PMID- 29166589
TI  - Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors
      Independently Produce Functionally Distinct Monocytes.
AB  - Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors
      (MDPs) produce monocytes during homeostasis and in response to increased demand
      during infection. Both progenitor populations are thought to derive from common
      myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP
      monocyte) is presumed to underlie monocyte differentiation. Here, however, we
      demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs
      and MDPs produced monocytes via similar but distinct monocyte-committed
      progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene
      expression signatures that were defined by their origins and impacted their
      function. GMPs produced a subset of "neutrophil-like" monocytes, whereas MDPs
      gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells.
      GMPs and MDPs were also independently mobilized to produce specific combinations
      of myeloid cell types following the injection of microbial components. Thus, the
      balance of GMP and MDP differentiation shapes the myeloid cell repertoire during
      homeostasis and following infection.

PMID- 29166590
TI  - Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin
      Secretion through Myeloid Cell Retinoic Acid Production.
AB  - Pancreatic-islet inflammation contributes to the failure of beta cell insulin
      secretion during obesity and type 2 diabetes. However, little is known about the
      nature and function of resident immune cells in this context or in homeostasis.
      Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and
      enhanced by a diabetes milieu (glucose, IL-1beta, and palmitate). IL-33 promoted
      beta cell function through islet-resident group 2 innate lymphoid cells (ILC2s)
      that elicited retinoic acid (RA)-producing capacities in macrophages and
      dendritic cells via the secretion of IL-13 and colony-stimulating factor 2. In
      turn, local RA signaled to the beta cells to increase insulin secretion. This IL
      33-ILC2 axis was activated after acute beta cell stress but was defective during
      chronic obesity. Accordingly, IL-33 injections rescued islet function in obese
      mice. Our findings provide evidence that an immunometabolic crosstalk between
      islet-derived IL-33, ILC2s, and myeloid cells fosters insulin secretion.

PMID- 29166591
TI  - A CD103+ Conventional Dendritic Cell Surveillance System Prevents Development of
      Overt Heart Failure during Subclinical Viral Myocarditis.
AB  - Innate and adaptive immune cells modulate heart failure pathogenesis during viral
      myocarditis, yet their identities and functions remain poorly defined. We
      utilized a combination of genetic fate mapping, parabiotic, transcriptional, and
      functional analyses and demonstrated that the heart contained two major
      conventional dendritic cell (cDC) subsets, CD103+ and CD11b+, which
      differentially relied on local proliferation and precursor recruitment to
      maintain their tissue residency. Following viral infection of the myocardium,
      cDCs accumulated in the heart coincident with monocyte infiltration and loss of
      resident reparative embryonic-derived cardiac macrophages. cDC depletion
      abrogated antigen-specific CD8+ T cell proliferative expansion, transforming
      subclinical cardiac injury to overt heart failure. These effects were mediated by
      CD103+ cDCs, which are dependent on the transcription factor BATF3 for their
      development. Collectively, our findings identified resident cardiac cDC subsets,
      defined their origins, and revealed an essential role for CD103+ cDCs in antigen
      specific T cell responses during subclinical viral myocarditis.

PMID- 29166593
TI  - Neural correlates of improvements in personality and behavior following a
      neurological event.
AB  - Research on changes in personality and behavior following brain damage has
      focused largely on negative outcomes, such as increased irritability, moodiness,
      and social inappropriateness. However, clinical observations suggest that some
      patients may actually show positive personality and behavioral changes following
      a neurological event. In the current work, we investigated neuroanatomical
      correlates of positive personality and behavioral changes following a discrete
      neurological event (e.g., stroke, benign tumor resection). Patients (N = 97) were
      rated by a well-known family member or friend on five domains of personality and
      behavior: social behavior, irascibility, hypo-emotionality, distress, and
      executive functioning. Ratings were acquired during the chronic epoch of
      recovery, when psychological status was stabilized. We identified patients who
      showed positive changes in personality and behavior in one or more domains of
      functioning. Lesion analyses indicated that positive changes in personality and
      behavior were most consistently related to damage to the bilateral frontal polar
      regions and the right anterior dorsolateral prefrontal region. These findings
      support the conclusion that improvements in personality and behavior can occur
      after a neurological event, and that such changes have systematic neuroanatomical
      correlates. Patients who showed positive changes in personality and behavior
      following a neurological event were rated as having more disturbed functioning
      prior to the event. Our study may be taken as preliminary evidence that
      improvements in personality and behavior following a neurological event may
      involve dampening of (premorbidly) more extreme expressions of emotion.

PMID- 29166592
TI  - HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the
      Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage.
AB  - Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env)
      develop during natural infection can help guide the rational design of an HIV
      vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab
      Env co-evolution that led to development of neutralization breadth. The lineage
      Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of
      25 amino acids, among the shortest known for this class of Abs, and achieved
      breadth with only 10% nucleotide somatic hypermutation and no insertions or
      deletions. The data suggested a role for Env glycoform heterogeneity in the
      activation of the lineage germline B cell. Finally, we showed that localized
      diversity at key V2 epitope residues drove bnAb maturation toward breadth,
      mirroring the Env evolution pattern described for another donor who developed V2
      apex targeting bnAbs. Overall, these findings suggest potential strategies for
      vaccine approaches based on germline-targeting and serial immunogen design.

PMID- 29166594
TI  - Individual differences in processing emotional images after reading disgusting
      and neutral sentences.
AB  - The present study examined the extent to which Event Related Potentials (ERPs)
      evoked by disgusting, threatening and neutral photographic images were influenced
      by disgust propensity, disgust sensitivity and attentional control following
      exposure to disgusting information. Emotional cognition was manipulated by
      instructing participants to remember either disgusting or neutral sentences;
      participants in both groups then viewed emotional images while ERPs were
      recorded. Disgust propensity was associated with a reduced Late Positive
      Potential (LPP) gap between threatening and neutral stimuli (an effect driven by
      a rise in the LPP for neutral images) but only amongst individuals who were
      exposed to disgusting sentences. The typical LPP increase for disgust over
      neutral was reduced by attentional shifting capacity but only for individuals who
      were not previously exposed to disgust. There was also a persistent occipital
      shifted late positivity that was enhanced for disgust for the entire LPP window
      and was independent of exposure. Results suggest that emotion specific ERP
      effects can emerge within the broad unpleasant emotional category in conjunction
      with individual differences and prior emotional exposure. These results have
      important implications for the ways in which the perception of emotion is
      impacted by short term cognitive influences and longer term individual
      differences.

PMID- 29166595
TI  - Positive and Negative Regulation of the Master Metabolic Regulator mTORC1 by Two
      Families of Legionella pneumophila Effectors.
AB  - All pathogens must acquire nutrients from their hosts. The intracellular
      bacterial pathogen Legionella pneumophila, the etiological agent of Legionnaires'
      disease, requires host amino acids for growth within cells. The mechanistic
      target of rapamycin complex 1 (mTORC1) is an evolutionarily conserved master
      regulator of host amino acid metabolism. Here, we identify two families of
      translocated L. pneumophila effector proteins that exhibit opposing effects on
      mTORC1 activity. The Legionella glucosyltransferase (Lgt) effector family
      activates mTORC1, through inhibition of host translation, whereas the SidE/SdeABC
      (SidE) effector family acts as mTORC1 inhibitors. We demonstrate that a common
      activity of both effector families is to inhibit host translation. We propose
      that the Lgt and SidE families of effectors work in concert to liberate host
      amino acids for consumption by L. pneumophila.

PMID- 29166596
TI  - The GCN2-ATF4 Signaling Pathway Induces 4E-BP to Bias Translation and Boost
      Antimicrobial Peptide Synthesis in Response to Bacterial Infection.
AB  - Bacterial infection often leads to suppression of mRNA translation, but hosts are
      nonetheless able to express immune response genes through as yet unknown
      mechanisms. Here, we use a Drosophila model to demonstrate that antimicrobial
      peptide (AMP) production during infection is paradoxically stimulated by the
      inhibitor of cap-dependent translation, 4E-BP (eIF4E-binding protein; encoded by
      the Thor gene). We found that 4E-BP is induced upon infection with pathogenic
      bacteria by the stress-response transcription factor ATF4 and its upstream
      kinase, GCN2. Loss of gcn2, atf4, or 4e-bp compromised immunity. While AMP
      transcription is unaffected in 4e-bp mutants, AMP protein levels are
      substantially reduced. The 5' UTRs of AMPs score positive in cap-independent
      translation assays, and this cap-independent activity is enhanced by 4E-BP. These
      results are corroborated in vivo using transgenic 5' UTR reporters. These
      observations indicate that ATF4-induced 4e-bp contributes to innate immunity by
      biasing mRNA translation toward cap-independent mechanisms, thus enhancing AMP
      synthesis.

PMID- 29166597
TI  - Mammalian HP1 Isoforms Have Specific Roles in Heterochromatin Structure and
      Organization.
AB  - HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms
      HP1alpha, HP1beta, and HP1gamma play different roles in genome stability, but
      their precise role in heterochromatin structure is unclear. Analysis of Hp1alpha
      /-, Hp1beta-/-, and Hp1gamma-/- MEFs show that HP1 proteins have both redundant
      and unique functions within pericentric heterochromatin (PCH) and also act
      globally throughout the genome. HP1alpha confines H4K20me3 and H3K27me3 to
      regions within PCH, while its absence results in a global hyper-compaction of
      chromatin associated with a specific pattern of mitotic defects. In contrast,
      HP1beta is functionally associated with Suv4-20h2 and H4K20me3, and its loss
      induces global chromatin decompaction and an abnormal enrichment of CTCF in PCH
      and other genomic regions. Our work provides insight into the roles of HP1
      proteins in heterochromatin structure and genome stability.

PMID- 29166598
TI  - Biological Significance of the Suppression of Oxidative Phosphorylation in
      Induced Pluripotent Stem Cells.
AB  - We discovered that induced pluripotent stem cell (iPSC) clones generated from
      aged tissue donors (A-iPSCs) fail to suppress oxidative phosphorylation. Compared
      to embryonic stem cells (ESCs) and iPSCs generated from young donors (Y-iPSCs), A
      iPSCs show poor expression of the pluripotent stem cell-specific glucose
      transporter 3 (GLUT3) and impaired glucose uptake, making them unable to support
      the high glucose demands of glycolysis. Persistent oxidative phosphorylation in A
      iPSCs generates higher levels of reactive oxygen species (ROS), which leads to
      excessive elevation of glutathione (a ROS-scavenging metabolite) and a blunted
      DNA damage response. These phenotypes were recapitulated in Y-iPSCs by inhibiting
      pyruvate dehydrogenase kinase (PDK) or supplying citrate to activate oxidative
      phosphorylation. In addition, oxidative phosphorylation in A-iPSC clones depletes
      citrate, a nuclear source of acetyl group donors for histone acetylation; this
      consequently alters histone acetylation status. Expression of GLUT3 in A-iPSCs
      recovers the metabolic defect, DNA damage response, and histone acetylation
      status.

PMID- 29166599
TI  - Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal
      Refinement of Climbing Fiber Network.
AB  - Neural circuits undergo massive refinements during postnatal development. In the
      developing cerebellum, the climbing fiber (CF) to Purkinje cell (PC) network is
      drastically reshaped by eliminating early-formed redundant CF to PC synapses. To
      investigate the impact of CF network refinement on PC population activity during
      postnatal development, we monitored spontaneous CF responses in neighboring PCs
      and the activity of populations of nearby CF terminals using in vivo two-photon
      calcium imaging. Population activity is highly synchronized in newborn mice, and
      the degree of synchrony gradually declines during the first postnatal week in PCs
      and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage
      gated calcium channel or glutamate receptor delta2, in which CF network
      refinement is severely impaired, exhibit an abnormally high level of synchrony in
      PC population activity. These results suggest that CF network refinement is a
      structural basis for developmental desynchronization and maturation of PC
      population activity.

PMID- 29166600
TI  - Dopamine Receptor DAMB Signals via Gq to Mediate Forgetting in Drosophila.
AB  - Prior studies have shown that aversive olfactory memory is acquired by dopamine
      acting on a specific receptor, dDA1, expressed by mushroom body neurons. Active
      forgetting is mediated by dopamine acting on another receptor, Damb, expressed by
      the same neurons. Surprisingly, prior studies have shown that both receptors
      stimulate cyclic AMP (cAMP) accumulation, presenting an enigma of how mushroom
      body neurons distinguish between acquisition and forgetting signals. Here, we
      surveyed the spectrum of G protein coupling of dDA1 and Damb, and we confirmed
      that both receptors can couple to Gs to stimulate cAMP synthesis. However, the
      Damb receptor uniquely activates Gq to mobilize Ca2+ signaling with greater
      efficiency and dopamine sensitivity. The knockdown of Galphaq with RNAi in the
      mushroom bodies inhibits forgetting but has no effect on acquisition. Our
      findings identify a Damb/Gq-signaling pathway that stimulates forgetting and
      resolves the opposing effects of dopamine on acquisition and forgetting.

PMID- 29166601
TI  - Triple Function of Synaptotagmin 7 Ensures Efficiency of High-Frequency
      Transmission at Central GABAergic Synapses.
AB  - Synaptotagmin 7 (Syt7) is thought to be a Ca2+ sensor that mediates asynchronous
      transmitter release and facilitation at synapses. However, Syt7 is strongly
      expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the
      output synapses of these neurons produce only minimal asynchronous release and
      show depression rather than facilitation. To resolve this apparent contradiction,
      we examined the effects of genetic elimination of Syt7 on synaptic transmission
      at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum. Our
      results indicate that at the BC-PC synapse, Syt7 contributes to asynchronous
      release, pool replenishment, and facilitation. In combination, these three
      effects ensure efficient transmitter release during high-frequency activity and
      guarantee frequency independence of inhibition. Our results identify a distinct
      function of Syt7: ensuring the efficiency of high-frequency inhibitory synaptic
      transmission.

PMID- 29166602
TI  - Mucus Detachment by Host Metalloprotease Meprin beta Requires Shedding of Its
      Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB.
AB  - The host metalloprotease meprin beta is required for mucin 2 (MUC2) cleavage,
      which drives intestinal mucus detachment and prevents bacterial overgrowth. To
      gain access to the cleavage site in MUC2, meprin beta must be proteolytically
      shed from epithelial cells. Hence, regulation of meprin beta shedding and
      activation is important for physiological and pathophysiological conditions.
      Here, we demonstrate that meprin beta activation and shedding are mutually
      exclusive events. Employing ex vivo small intestinal organoid and cell culture
      experiments, we found that ADAM-mediated shedding is restricted to the inactive
      pro-form of meprin beta and is completely inhibited upon its conversion to the
      active form at the cell surface. This strict regulation of meprin beta activity
      can be overridden by pathogens, as demonstrated for the bacterial protease Arg
      gingipain (RgpB). This secreted cysteine protease potently converts membrane
      bound meprin beta into its active form, impairing meprin beta shedding and its
      function as a mucus-detaching protease.

PMID- 29166603
TI  - Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction
      Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation.
AB  - Lymphocytes cross vascular boundaries via either disrupted tight junctions (TJs)
      or caveolae to induce tissue inflammation. In the CNS, Th17 lymphocytes cross the
      blood-brain barrier (BBB) before Th1 cells; yet this differential crossing is
      poorly understood. We have used intravital two-photon imaging of the spinal cord
      in wild-type and caveolae-deficient mice with fluorescently labeled endothelial
      tight junctions to determine how tight junction remodeling and caveolae regulate
      CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis
      (EAE) model for multiple sclerosis. We find that dynamic tight junction
      remodeling occurs early in EAE but does not depend upon caveolar transport.
      Moreover, Th1, but not Th17, lymphocytes are significantly reduced in the
      inflamed CNS of mice lacking caveolae. Therefore, tight junction remodeling
      facilitates Th17 migration across the BBB, whereas caveolae promote Th1 entry
      into the CNS. Moreover, therapies that target both tight junction degradation and
      caveolar transcytosis may limit lymphocyte infiltration during inflammation.

PMID- 29166604
TI  - Capture of Dense Core Vesicles at Synapses by JNK-Dependent Phosphorylation of
      Synaptotagmin-4.
AB  - Delivery of neurotrophins and neuropeptides via long-range trafficking of dense
      core vesicles (DCVs) from the cell soma to nerve terminals is essential for
      synapse modulation and circuit function. But the mechanism by which transiting
      DCVs are captured at specific sites is unknown. Here, we discovered that
      Synaptotagmin-4 (Syt4) regulates the capture and spatial distribution of DCVs in
      hippocampal neurons. We found that DCVs are highly mobile and undergo long-range
      translocation but switch directions only at the distal ends of axons, revealing a
      circular trafficking pattern. Phosphorylation of serine 135 of Syt4 by JNK steers
      DCV trafficking by destabilizing Syt4-Kif1A interaction, leading to a transition
      from microtubule-dependent DCV trafficking to capture at en passant presynaptic
      boutons by actin. Furthermore, neuronal activity increased DCV capture via JNK
      dependent phosphorylation of the S135 site of Syt4. Our data reveal a mechanism
      that ensures rapid, site-specific delivery of DCVs to synapses.

PMID- 29166605
TI  - L-Type Voltage-Gated Ca2+ Channels Regulate Synaptic-Activity-Triggered Recycling
      Endosome Fusion in Neuronal Dendrites.
AB  - The repertoire and abundance of proteins displayed on the surface of neuronal
      dendrites are tuned by regulated fusion of recycling endosomes (REs) with the
      dendritic plasma membrane. While this process is critical for neuronal function
      and plasticity, how synaptic activity drives RE fusion remains unexplored. We
      demonstrate a multistep fusion mechanism that requires Ca2+ from distinct
      sources. NMDA receptor Ca2+ initiates RE fusion with the plasma membrane, while L
      type voltage-gated Ca2+ channels (L-VGCCs) regulate whether fused REs collapse
      into the membrane or reform without transferring their cargo to the cell surface.
      Accordingly, NMDA receptor activation triggered AMPA-type glutamate receptor
      trafficking to the dendritic surface in an L-VGCC-dependent manner. Conversely,
      potentiating L-VGCCs enhanced AMPA receptor surface expression only when NMDA
      receptors were also active. Thus L-VGCCs play a role in tuning activity-triggered
      surface expression of key synaptic proteins by gating the mode of RE fusion.

PMID- 29166606
TI  - SUMOylation Promotes Nuclear Import and Stabilization of Polo-like Kinase 1 to
      Support Its Mitotic Function.
AB  - As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly
      coordinated and multi-layered regulation. However, the pathways that control
      PLK1's activity and function have just begun to be elucidated. PLK1 has recently
      been shown to be functionally modulated by post-translational modifications
      (PTMs), including phosphorylation and ubiquitination. Herein, we report that
      SUMOylation plays an essential role in regulating PLK1's mitotic function. We
      found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation
      by CDK1/cyclin B. By in vivo and in vitro SUMOylation assays, PLK1 was identified
      as a physiologically relevant small ubiquitin-related modifier (SUMO)-targeted
      protein, preferentially modified by SUMO-1. We further showed that K492 on PLK1
      is essential for SUMOylation. SUMOylation causes PLK1's nuclear import and
      significantly increases its protein stability, both of which are critical for
      normal mitotic progression and genomic integrity. Our findings suggest that
      SUMOylation is an important regulatory mechanism governing PLK1's mitotic
      function.

PMID- 29166607
TI  - Kdm2b Regulates Somatic Reprogramming through Variant PRC1 Complex-Dependent
      Function.
AB  - Polycomb repressive complex 1 (PRC1) plays essential roles in cell-fate
      determination. Recent studies have found that the composition of mammalian PRC1
      is particularly varied and complex; however, little is known about the functional
      consequences of these variant PRC1 complexes on cell-fate determination. Here, we
      show that Kdm2b promotes Oct4-induced somatic reprogramming through recruitment
      of a variant PRC1 complex (PRC1.1) to CpG islands (CGIs). Furthermore, we find
      that bone morphogenetic protein (BMP) represses Oct4/Kdm2b-induced somatic
      reprogramming selectively. Mechanistically, BMP-SMAD pathway attenuates PRC1.1
      occupation and H2AK119 ubiquitination at genes linked to development, resulting
      in the expression of mesendodermal factors such as Sox17 and a consequent
      suppression of somatic reprogramming. These observations reveal that PRC1.1
      participates in the establishment of pluripotency and identify BMP4 signaling as
      a modulator of PRC1.1 function.

PMID- 29166608
TI  - S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC
      Based Parkinson's Disease Models.
AB  - Mutations in PARK6 (PINK1) and PARK2 (Parkin) are linked to rare familial cases
      of Parkinson's disease (PD). Mutations in these genes result in pathological
      dysregulation of mitophagy, contributing to neurodegeneration. Here, we report
      that environmental factors causing a specific posttranslational modification on
      PINK1 can mimic these genetic mutations. We describe a molecular mechanism for
      impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1).
      Mitochondrial insults simulating age- or environmental-related stress lead to
      increased SNO-PINK1, inhibiting its kinase activity. SNO-PINK1 decreases Parkin
      translocation to mitochondrial membranes, disrupting mitophagy in cell lines and
      human-iPSC-derived neurons. We find levels of SNO-PINK1 in brains of alpha
      synuclein transgenic PD mice similar to those in cell-based models, indicating
      the pathophysiological relevance of our findings. Importantly, SNO-PINK1-mediated
      deficits in mitophagy contribute to neuronal cell death. These results reveal a
      direct molecular link between nitrosative stress, SNO-PINK1 formation, and
      mitophagic dysfunction that contributes to the pathogenesis of PD.

PMID- 29166609
TI  - GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in
      Glioblastoma.
AB  - A mesenchymal transition occurs both during the natural evolution of glioblastoma
      (GBM) and in response to therapy. Here, we report that the adhesion G-protein
      coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and
      radioresistance. GPR56 is enriched in proneural and classical GBMs and is lost
      during their transition toward a mesenchymal subtype. GPR56 loss of function
      promotes mesenchymal differentiation and radioresistance of glioma initiating
      cells both in vitro and in vivo. Accordingly, a low GPR56-associated signature is
      prognostic of a poor outcome in GBM patients even within non-G-CIMP GBMs.
      Mechanistically, we reveal GPR56 as an inhibitor of the nuclear factor kappa B
      (NF-kappaB) signaling pathway, thereby providing the rationale by which this
      receptor prevents mesenchymal differentiation and radioresistance. A pan-cancer
      analysis suggests that GPR56 might be an inhibitor of the mesenchymal transition
      across multiple tumor types beyond GBM.

PMID- 29166610
TI  - CISD2 Haploinsufficiency Disrupts Calcium Homeostasis, Causes Nonalcoholic Fatty
      Liver Disease, and Promotes Hepatocellular Carcinoma.
AB  - CISD2 is located within the chromosome 4q region frequently deleted in
      hepatocellular carcinoma (HCC). Mice with Cisd2 heterozygous deficiency develop a
      phenotype similar to the clinical manifestation of nonalcoholic fatty liver
      disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Cisd2 haploinsufficiency
      causes a low incidence (20%) of spontaneous HCC and promotes HBV-associated and
      DEN-induced HCC; conversely, 2-fold overexpression of Cisd2 suppresses HCC in
      these models. Mechanistically, Cisd2 interacts with Serca2b and mediates its Ca2+
      pump activity via modulation of Serca2b oxidative modification, which regulates
      ER Ca2+ uptake and maintains intracellular Ca2+ homeostasis in the hepatocyte.
      CISD2 haploinsufficiency disrupts calcium homeostasis, causing ER stress and
      subsequent NAFLD and NASH. Hemizygous deletion and decreased expression of CISD2
      are detectable in a substantial fraction of human HCC specimens. These findings
      substantiate CISD2 as a haploinsufficient tumor suppressor and highlights Cisd2
      as a drug target when developing therapies to treat NAFLD/NASH and prevent HCC.

PMID- 29166611
TI  - CCR5 Directs the Mobilization of CD11b+Gr1+Ly6Clow Polymorphonuclear Myeloid
      Cells from the Bone Marrow to the Blood to Support Tumor Development.
AB  - Cells of hematopoietic origin can be subdivided into cells of the lymphoid
      lineage and those of the myeloid lineage, among which are myeloid-derived
      suppressor cells (MDSCs). The MDSCs can be further divided into CD11b+Ly6G-Ly6Chi
      monocytic (Mo) MDSCs and CD11b+Ly6G+Ly6Clow polymorphonuclear (PMN) MDSCs. Both
      subtypes support tumor growth and suppress anti-tumor immunity. Their
      accumulation at the tumor site includes mobilization from the bone marrow to the
      blood followed by colonization at the tumor site. The present study examines the
      mechanism by which PMN-MDSCs are mobilized from the BM to the blood to later
      accumulate at the tumor site. We show that the chemokine receptor CCR5 is a key
      driver of this event. We also show that, beyond chemoattraction, the interaction
      between CCR5 and its ligands promotes the proliferation of CCR5+ PMN-MDSCs at the
      BM and, later, potentiates their immune-suppressive activities at the tumor site
      in part by inducing arginase-1.

PMID- 29166612
TI  - Impediment of Replication Forks by Long Non-coding RNA Provokes Chromosomal
      Rearrangements by Error-Prone Restart.
AB  - Naturally stalled replication forks are considered to cause structurally abnormal
      chromosomes in tumor cells. However, underlying mechanisms remain speculative, as
      capturing naturally stalled forks has been a challenge. Here, we captured
      naturally stalled forks in tumor cells and delineated molecular processes
      underlying the structural evolution of circular mini-chromosomes (double-minute
      chromosomes; DMs). Replication forks stalled on the DM by the co-directional
      collision with the transcription machinery for long non-coding RNA. RPA, BRCA2,
      and DNA polymerase eta (Poleta) were recruited to the stalled forks. The
      recruitment of Poleta was critical for replication to continue, as Poleta
      knockdown resulted in DM loss. Rescued stalled forks were error-prone and
      switched replication templates repeatedly to create complex fusions of multiple
      short genomic segments. In mice, such complex fusions circularized the genomic
      region surrounding MYC to create a DM during tumorigenesis. Our results define a
      molecular path that guides stalled replication forks to complex chromosomal
      rearrangements.

PMID- 29166613
TI  - Niche Cadherins Control the Quiescence-to-Activation Transition in Muscle Stem
      Cells.
AB  - Many adult stem cells display prolonged quiescence, promoted by cues from their
      niche. Upon tissue damage, a coordinated transition to the activated state is
      required because non-physiological breaks in quiescence often lead to stem cell
      depletion and impaired regeneration. Here, we identify cadherin-mediated adhesion
      and signaling between muscle stem cells (satellite cells [SCs]) and their
      myofiber niche as a mechanism that orchestrates the quiescence-to-activation
      transition. Conditional removal of N-cadherin and M-cadherin in mice leads to a
      break in SC quiescence, with long-term expansion of a regeneration-proficient SC
      pool. These SCs have an incomplete disruption of the myofiber-SC adhesive
      junction and maintain niche residence and cell polarity, yet show properties of
      SCs in a state of transition from quiescence toward full activation. Among these
      is nuclear localization of beta-catenin, which is necessary for this phenotype.
      Injury-induced perturbation of niche adhesive junctions is therefore a likely
      first step in the quiescence-to-activation transition.

PMID- 29166614
TI  - Critical Modulation of Hematopoietic Lineage Fate by Hepatic Leukemia Factor.
AB  - A gradual restriction in lineage potential of multipotent stem/progenitor cells
      is a hallmark of adult hematopoiesis, but the underlying molecular events
      governing these processes remain incompletely understood. Here, we identified
      robust expression of the leukemia-associated transcription factor hepatic
      leukemia factor (Hlf) in normal multipotent hematopoietic progenitors, which was
      rapidly downregulated upon differentiation. Interference with its normal
      downregulation revealed Hlf as a strong negative regulator of lymphoid
      development, while remaining compatible with myeloid fates. Reciprocally, we
      observed rapid lymphoid commitment upon reduced Hlf activity. The arising
      phenotypes resulted from Hlf binding to active enhancers of myeloid-competent
      cells, transcriptional induction of myeloid, and ablation of lymphoid gene
      programs, with Hlf induction of nuclear factor I C (Nfic) as a functionally
      relevant target gene. Thereby, our studies establish Hlf as a key regulator of
      the earliest lineage-commitment events at the transition from multipotency to
      lineage-restricted progeny, with implications for both normal and malignant
      hematopoiesis.

PMID- 29166615
TI  - Olfactory-Experience- and Developmental-Stage-Dependent Control of CPEB4
      Regulates c-Fos mRNA Translation for Granule Cell Survival.
AB  - Mammalian olfactory bulbs (OBs) require continuous replenishment of interneurons
      (mainly granule cells [GCs]) to support local circuits throughout life. Two
      spatiotemporally distinct waves of postnatal neurogenesis contribute to expanding
      and maintaining the GC pool. Although neonate-born GCs have a higher survival
      rate than adult-born GCs, the molecular mechanism underlying this survival
      remains unclear. Here, we find that cytoplasmic polyadenylation element-binding
      protein 4 (CPEB4) acts as a survival factor exclusively for early postnatal GCs.
      In mice, during the first 2 postnatal weeks, olfactory experience initiated CPEB4
      activated c-Fos mRNA translation. In CPEB4-knockout mice, c-FOS insufficiency
      reduced neurotrophic signaling to impair GC survival and cause OB hypoplasia.
      Both cyclic AMP responsive element binding protein (CREB)-dependent transcription
      and CPEB4-promoted translation support c-FOS expression early postnatal OBs but
      disengage in adult OBs. Activity-related c-FOS synthesis and GC survival are thus
      developmentally controlled by distinct molecular mechanisms to govern OB growth.

PMID- 29166616
TI  - The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T
      Cells.
AB  - The local environment may affect the development and function of tissue-resident
      T regulatory cells (Tregs), which are crucial for controlling inflammation.
      Although the aryl hydrocarbon receptor (Ahr), an environmental sensor, is
      expressed by Tregs, its role in Treg cell development and/or function remains
      elusive. Here, we generated mouse genetic models to ablate or activate Ahr
      expression specifically in Tregs. We showed that Ahr was expressed more
      abundantly by peripherally induced Tregs (pTregs) in the gut and that its
      expression was independent of microbiota. Ahr was important for Treg gut homing
      and function. Ahr inhibited pro-inflammatory cytokines produced by Tregs but was
      dispensable for Treg stability. Furthermore, Ahr-expressing Tregs had enhanced in
      vivo suppressive activity compared with Tregs lacking Ahr expression in a T cell
      transfer model of colitis. Our data suggest that Ahr signaling in Tregs may be
      important for gut immune homeostasis.

PMID- 29166617
TI  - Spatiotemporal Proteomic Profiling of Huntington's Disease Inclusions Reveals
      Widespread Loss of Protein Function.
AB  - Aggregation of polyglutamine-expanded huntingtin exon 1 (HttEx1) in Huntington's
      disease (HD) proceeds from soluble oligomers to late-stage inclusions. The nature
      of the aggregates and how they lead to neuronal dysfunction is not well
      understood. We employed mass spectrometry (MS)-based quantitative proteomics to
      dissect spatiotemporal mechanisms of neurodegeneration using the R6/2 mouse model
      of HD. Extensive remodeling of the soluble brain proteome correlated with
      insoluble aggregate formation during disease progression. In-depth and
      quantitative characterization of the aggregates uncovered an unprecedented
      complexity of several hundred proteins. Sequestration to aggregates depended on
      protein expression levels and sequence features such as low-complexity regions or
      coiled-coil domains. In a cell-based HD model, overexpression of a subset of the
      sequestered proteins in most cases rescued viability and reduced aggregate size.
      Our spatiotemporally resolved proteome resource of HD progression indicates that
      widespread loss of cellular protein function contributes to aggregate-mediated
      toxicity.

PMID- 29166618
TI  - iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti
      amyloid beta Combination for Alzheimer's Disease.
AB  - In the process of drug development, in vitro studies do not always adequately
      predict human-specific drug responsiveness in clinical trials. Here, we applied
      the advantage of human iPSC-derived neurons, which offer human-specific drug
      responsiveness, to screen and evaluate therapeutic candidates for Alzheimer's
      disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we
      established a robust and reproducible assay for amyloid beta peptide (Abeta), a
      pathogenic molecule in AD, and screened a pharmaceutical compound library. We
      acquired 27 Abeta-lowering screen hits, prioritized hits by chemical structure
      based clustering, and selected 6 leading compounds. Next, to maximize the anti
      Abeta effect, we selected a synergistic combination of bromocriptine, cromolyn,
      and topiramate as an anti-Abeta cocktail. Finally, using neurons from familial
      and sporadic AD patients, we found that the cocktail showed a significant and
      potent anti-Abeta effect on patient cells. This human iPSC-based platform
      promises to be useful for AD drug development.

PMID- 29166619
TI  - Extensive Homeostatic T Cell Phenotypic Variation within the Collaborative Cross.
AB  - The Collaborative Cross (CC) is a panel of reproducible recombinant inbred mouse
      strains with high levels of standing genetic variation, affording an
      unprecedented opportunity to perform experiments in a small animal model
      containing controlled genetic diversity while allowing for genetic replicates.
      Here, we advance the utility of this unique mouse resource for immunology
      research because it allows for both examination and genetic dissection of
      mechanisms behind adaptive immune states in mice with distinct and defined
      genetic makeups. This approach is based on quantitative trait locus mapping:
      identifying genetically variant genome regions associated with phenotypic
      variance in traits of interest. Furthermore, the CC can be utilized for mouse
      model development; distinct strains have unique immunophenotypes and immune
      properties, making them suitable for research on particular diseases and
      infections. Here, we describe variations in cellular immune phenotypes across F1
      crosses of CC strains and reveal quantitative trait loci responsible for several
      immune phenotypes.

PMID- 29166620
TI  - A Cell-Line-Specific Atlas of PARP-Mediated Protein Asp/Glu-ADP-Ribosylation in
      Breast Cancer.
AB  - PARP1 plays a critical role in regulating many biological processes linked to
      cellular stress responses. Although DNA strand breaks are potent stimuli of PARP1
      enzymatic activity, the context-dependent mechanism regulating PARP1 activation
      and signaling is poorly understood. We performed global characterization of the
      PARP1-dependent, Asp/Glu-ADP-ribosylated proteome in a panel of cell lines
      originating from benign breast epithelial cells, as well as common subtypes of
      breast cancer. From these analyses, we identified 503 specific ADP-ribosylation
      sites on 322 proteins. Despite similar expression levels, PARP1 is differentially
      activated in these cell lines under genotoxic conditions, which generates
      signaling outputs with substantial heterogeneity. By comparing protein abundances
      and ADP-ribosylation levels, we could dissect cell-specific PARP1 targets that
      are driven by unique expression patterns versus cell-specific regulatory
      mechanisms of PARylation. Intriguingly, PARP1 modifies many proteins in a cell
      specific manner, including those involved in transcriptional regulation, mRNA
      metabolism, and protein translation.

PMID- 29166621
TI  - Lifestyle transitions and adaptive pathogenesis of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa acute and chronic infections are of great concern to human
      health, especially in hospital settings. It is currently assumed that P.
      aeruginosa has two antagonistic pathogenic strategies that parallel two different
      lifestyles; free-living cells are predominantly cytotoxic and induce an acute
      inflammatory reaction, while biofilm-forming communities cause refractory chronic
      infections. Recent findings suggest that the planktonic-to-sessile transition is
      a complex, reversible and overall dynamic differentiation process. Here, we
      examine how the Gac/Rsm regulatory cascade, a key player in this lifestyle
      switch, endows P. aeruginosa with both a permissive lifecycle in nature and
      flexible virulence strategy during infection.

PMID- 29166622
TI  - Morphological characteristics and variations of the human quadratus plantae
      muscle.
AB  - The quadratus plantae (QP) is a highly variable structure. A number of partly
      inexact descriptions of this entity have been provided in textbooks of anatomy.
      Although several authors have examined the QP, its exact site of origin and type
      of insertion have hitherto not been specified. The aim of this study has been to
      provide detailed qualitative and quantitative data about the number of heads,
      points of origin, and type of insertion of the QP. The QP in both feet of 50
      formalin-fixed specimens of body donors (25 men and women) were analyzed by gross
      anatomical dissection. It was composed of one (34%), two (57%) or three heads
      (9%). The latter condition was observed only in men. The lateral head was absent
      in 31 feet, and the medial head only in one right foot of a man. The medial head
      arose, amongst others, in 100% of the examined cases from the medial calcaneal
      surface, in 93% from the long plantar ligament and in 80% from the plantar
      calcaneocuboid ligament. The lateral head arose, amongst others, from the long
      plantar ligament in 90%, and from the lateral process of the calcaneal tuberosity
      in 64% of the examined feet. The type of insertion was always a mixture of at
      least two of three types; i.e. muscular (84%), tendinous (89%) and aponeurotic
      (45%). As additional findings, the flexor digitorum accessorius longus (FDAL) and
      the peroneocalcaneus internus (PCI) were observed in 12% of all individuals and
      in 20% of men. The present investigation revealed that the QP may be classified
      according to the number of heads, but no classification can be given for its
      points of origin or type of insertion. The present data are mandatory for
      anatomical and surgical practice and will hopefully lead to further imaging and
      biomechanical studies.

PMID- 29166623
TI  - Anticancer potential of ZnO nanoparticle-ferulic acid conjugate on Huh-7 and
      HepG2 cells and diethyl nitrosamine induced hepatocellular cancer on Wistar
      albino rat.
AB  - Drawbacks and limitations of recently available therapies to hepatocellular
      cancer (HCC) devoted the scientist to focus on emerging new strategies. ZnO
      nanoparticles (ZnONPs) based chemotherapeutics has been emanating as a promising
      approach to maximize therapeutic synergy facilitating the discovery of novel
      multitargeted combinations. In the present study we conjugated ZnONPs with
      ferulic acid (ZnONPs-FAC) characterized by computational, spectroscopic and
      microscopic techniques. In vitro anticancer potential has been evaluated by
      assessing cell viability, morphology, ROS generation, mitochondrial membrane
      permeability, comet assay, immunofluorescent staining of 8-OHdG, Ki67 and gamma
      H2AX, cell cycle analysis and western blot analysis and in vivo anticancer
      potential against DEN induced HCC was analyzed by histopathological and
      immunohistochemical methods. The results revealed that ZnONPs-FAC induces cell
      death through apoptosis and can suppress the DEN-induced HCC. Our study documents
      therapeutic potential of nanoparticle conjugated with phytochemicals, suggesting
      a new platform for combinatorial chemotherapy.

PMID- 29166624
TI  - Impact of processing methods on the dissolution of artemether from two non
      ordered mesoporous silicas.
AB  - Poor aqueous solubility is often linked with a poor dissolution rate and
      ultimately, limited bioavailability of pharmaceutical compounds. This study
      describes the application of mesoporous materials (Syloid 244 and Syloid AL1) in
      improving the dissolution rate of a drug with poor aqueous solubility, namely
      artemether, utilising different processing methods including physical mixing, co
      grinding and solid dispersions prepared by solvent evaporation and the
      lyophilisation technique. The prepared formulations were extensively
      characterised for their solid-state properties and the drug release attributes
      were studied. Differential scanning calorimetry and X-ray diffraction confirmed
      conversion of crystalline artemether into a disordered and amorphous form, whilst
      no intermolecular interactions were detected between artemether and silica. Both
      silica grades enhanced the dissolution rate of artemether in comparison with drug
      alone, for example from 17.43% (+/-0.87%) to 71.55% (+/-3.57%) after 120mins with
      lyophilisation and Syloid 244 at a 1:3 ratio. This enhancement was also dependant
      on the choice of processing method, for example, co-ground and lyophilised
      formulations prepared with Syloid 244 at 1:3 ratio produced the most extensive
      dissolution, thus endorsing the importance of materials as well as choice of
      formulation method.

PMID- 29166625
TI  - Ambient surface mass spectrometry-ion mobility spectrometry of intact proteins.
AB  - Ambient surface mass spectrometry encompasses a broad range of sampling and
      ionization techniques. To date, only a small subset of these, based on liquid
      microjunction extraction, have proven suitable for intact protein analysis from
      thin tissue sections. Liquid extraction surface analysis shows particular promise
      for this application. Recently, a range of ion mobility spectrometry approaches
      have been coupled with ambient mass spectrometry. Improvements in signal-to-noise
      ratios, decreased chemical noise and separation of molecular classes have been
      described for the analysis of various biological substrates. Similar benefits
      have been described for ambient mass spectrometry imaging studies. In this
      review, we discuss the application of ambient mass spectrometry and ion mobility
      spectrometry to the analysis of intact proteins, and discuss opportunities and
      challenges for the field.

PMID- 29166626
TI  - Non-covalent interactions between thio-caffeine derivatives and water-soluble
      porphyrin in ethanol-water environment.
AB  - To determine the binding interactions and ability to form the non-covalent
      systems, the association process between 5,10,15,20-tetrakis[4
      (trimethylammonio)phenyl]-21H,23H-porphine tetra-p-tosylate (H2TTMePP) and a
      series of five structurally diverse thio-caffeine analogues has been studied in
      ethanol and ethanol-water solutions, analyzing its absorption and steady-state
      fluorescence spectra. The porphyrin fluorescence lifetimes in the systems studied
      were established as well. During the titration with thio-caffeine compounds the
      slight bathochromic effect and considerable hypochromicity of the porphyrin Soret
      band maximum can be noted. The fluorescence quenching effect observed for
      interactions in H2TTMePP - thio-caffeine derivative systems, as well as the order
      of binding and fluorescence quenching constants (of 105-103mol-1) suggest the
      existence of the mechanism of static quenching due to the formation of non
      covalent and non-fluorescent stacking complexes. In all the systems studied the
      phenomenon of the fractional accessibility of the fluorophore for the quencher
      was observed as well. Additionally, the specific binding interactions, due to the
      changes in reaction environment polarity, can be observed. It was found that thio
      caffeine compounds can quench the porphyrin fluorescence according to the
      structure of thio-substituent in caffeine molecule. The obtained results can be
      potentially useful from scientific, therapeutic or environmental points of view.

PMID- 29166627
TI  - 1,4-Dioxane pollution at contaminated groundwater sites in western Germany and
      its distribution within a TCE plume.
AB  - An effective and sensitive method for the analysis of 1,4-dioxane in water has
      been available since 2008 (EPA 522). This method is increasingly being applied to
      investigate the distribution of 1,4-dioxane in the aquatic environment. However,
      there is a need for more information about the possible occurrence of 1,4-dioxane
      in groundwater in Europe in general, and in Germany in particular, where
      virtually no data have been collected so far. The possible contamination of
      groundwater with 1,4-dioxane is of relevance to Germany because up to 70% of
      Germany's drinking water is obtained from groundwater and about 17% from river
      bank filtrate, which contains variable proportions of groundwater. The aim of the
      present study is to investigate selected and representative groundwater sites in
      Germany that have suspected occurrences of 1,4-dioxane. Five of the sites are
      well known for their volatile chlorinated hydrocarbon contamination, two sites
      have representative landfill leachate characteristics, and one site is negatively
      impacted by a detergent manufacturing plant. The presence of 1,4-dioxane was
      observed at each of these sites. Measured maximum concentration values ranged
      from 0.15MUg/L to 152MUg/L. An aquifer containing a trichloroethylene (TCE) plume
      with 1,4-dioxane as a co-contaminant was investigated in more detail. A perfect
      match was found between the concentrations of 1,4-dioxane and TCE in the vertical
      and horizontal distribution profiles. The results indicate the necessity for
      investigating groundwater contamination by 1,4-dioxane at sites with known 1,1,1
      trichloroethane (TCA) and TCE contaminations, in landfill leachates, and at sites
      of detergent production.

PMID- 29166628
TI  - Biochar application for the remediation of heavy metal polluted land: A review of
      in situ field trials.
AB  - Polluted land is a global issue, especially for developing countries. It has been
      reported that soil amendment with biochar may reduce the bioavailability of a
      wide range of contaminants, including heavy metal(loids), potentially reclaiming
      contaminated soils for agricultural use. However, there have been only limited
      reports on the in situ application of biochar at the field scale. This review was
      devoted to providing preliminary scientific evidence from these field trials,
      based on a review of 29 publications involving field applications of biochar in 8
      different countries. The data show that biochar's effectiveness in reducing the
      impacts of pollution depends on a myriad of factors in the field, including the
      application time period, site-specific factors (e.g. climate, biochar dosage
      rate, and mixing depth), biochar feedstock type, and biochar properties. The
      results of this review indicate that biochar application can potentially reduce
      contaminant bioavailability in the field; for instance, a significant decrease
      (control normalized mean value=0.55) in the Cd enrichment of rice crops was
      observed. It was found that the use of biochar may help increase crop yields on
      polluted land, and thus reduce the amount of mineral fertilizer used in the
      field. However, in order to maximize the benefits of biochar addition, farmers
      need to accept that the dosage rates of mineral fertilizers should be reduced.
      This review also revealed that the effectiveness of biochar in mitigating
      pollution may decrease with time due to ageing factors, such as leaching of
      biochar alkalinity.

PMID- 29166632
TI  - How Old Are You? It's on Your Face!

PMID- 29166633
TI  - Range Extension and Behavioural Observations of the Recently Described Sheth's
      Dwarf Lemur (Cheirogaleus shethi).
AB  - Sheth's dwarf lemur, Cheirogaleus shethi, is a small, recently discovered
      nocturnal primate endemic to northern Madagascar. Unlike many other nocturnal
      lemurs, C. shethi lives sympatrically with morphologically similar species of its
      cryptic genus, making it difficult for biologists to determine its population
      density and distribution. Here, we present new data and observations of this
      species. During a series of rapid biodiversity assessments in the SAVA region of
      north-eastern Madagascar, we observed C. shethi in 10 different sites, 9 of which
      were not previously known to harbour C. shethi populations. More significantly, 2
      of these sites, in Analamanara, were situated approximately 20 km south of the
      previously known southern extremity of this species' distribution. This
      represents a large increase in the previously limited geographic range of this
      species. Moreover, our relatively high encounter rates at these sites suggest
      that C. shethi population densities may be high. We also observed C. shethi in
      human-altered (e.g., vanilla plantations) and non-forest, savannah environments,
      suggesting that this species can tolerate disturbed habitats. Our findings
      therefore provide important additional information on the distribution of C.
      shethi populations and highlight the necessity of further study for the
      conservation of this species.

PMID- 29166634
TI  - Sodium Prescription in the Prevention of Intradialytic Hypotension: New Insights
      into an Old Concept.
AB  - BACKGROUND: Sodium prescription in patients with intradialytic hypotension
      remains a challenge for the attending nephrologist, as it increases dialysate
      conductivity in hypotension-prone patients, thereby adding to dietary sodium
      levels. METHODS: New sodium prescription strategies are now available, including
      the use of a mathematical model to compute the sodium mass to be removed during
      dialysis as a physiological controller. RESULTS: This review describes the sodium
      load of patients with end-stage renal disease on chronic hemodialysis (HD) and
      discusses 2 strategies to remove excess sodium in patients prone to intradialytic
      hypotension, namely, Profiled HD and the hemodiafiltration Aequilibrium System.
      CONCLUSION: The Profiled HD and Aequilibrium System trial both proved effective
      in counteracting intradialytic hypotension.

PMID- 29166635
TI  - The Protean Neuropsychiatric and Vestibuloauditory Manifestations of
      Neurosarcoidosis.
AB  - BACKGROUND: A rare subset of sarcoidosis, neurosarcoidosis, is reported to occur
      in 5-7% of sarcoid patients and can manifest in a variety of ways. The most
      common are facial paralysis and optic neuritis, less commonly causing
      cochleovestibulopathy, blindness, anosmia, and other cranial nerve (CN) palsies.
      The sensory deficit may be severe and psychiatric symptoms may result from the
      effects of the disease or steroid treatment. Although MRI-compatible cochlear
      implants are now available, concerns about the feasibility of recoverable hearing
      with cochlear implantation in these patients as well as the practical difficulty
      of disease monitoring due to implant artifact must be considered. RESULTS: We
      present 3 recent cases from different institutions. The first is a 39-year-old
      man with a history of progressively worsening hearing loss, followed by visual
      loss, delusions, agitation, ataxia, and musical auditory hallucinations, diffuse
      leptomeningeal enhancement on MRI with a normal serum angiotensin-converting
      enzyme (ACE) level but elevated cerebrospinal fluid (CSF) ACE levels, suggesting
      neurosarcoidosis, was treated with corticosteroids, and underwent successful
      cochlear implantation. The second is a 36-year-old woman with rapid-onset
      horizontal diplopia, left mixed severe sensorineural hearing loss (SNHL) and
      tinnitus, diffuse leptomeningeal enhancement on MRI, and progressive palsy of the
      left CNs IV, VI, VII, IX, X and XI, with altered mental status requiring
      admission following high-dose intravenous corticosteroids. The third is a 15-year
      old boy who presented with sudden, bilateral, profound SNHL, recurrent headaches,
      and left facial weakness refractory to antivirals, ultimately diagnosed with
      neurosarcoidosis following an aborted cochlear implantation where diffuse
      inflammation was found, and histopathology revealed Schaumann bodies; he was
      treated with methotrexate and later underwent successful cochlear implantation.
      CONCLUSIONS: Neurosarcoidosis is an elusive diagnosis and can cause hearing loss
      and psychiatric symptoms. Cochlear implantation for patients with severe hearing
      loss should be considered once the diagnosis is confirmed, as it is possible to
      achieve a successful level of hearing. Psychiatric symptoms can manifest with the
      onset of neurosarcoidosis, result from CN deficits, or develop as a side effect
      from long-term, high-dose corticosteroids, and should be monitored carefully in
      patients with neurosarcoidosis.

PMID- 29166636
TI  - RegentK and Physiotherapy Support Knee Function after Anterior Cruciate Ligament
      Rupture without Surgery after 1 Year: A Randomized Controlled Trial.
AB  - BACKGROUND: Recent data have opened the debate on whether conservative treatment
      of anterior cruciate ligament (ACL) rupture might be an alternative treatment
      option to surgery. In a previous study, such a conservative treatment, i.e.
      'Regenerative Therapy According to Mohammed Khalifa' (RegentK), had shown good
      effects over physiotherapy. METHODS: This was a randomized controlled trial
      assessing the efficacy of 1 session of RegentK compared to the myofascial
      mobilization technique (MMT), another type of intensive physiotherapy, in 20
      patients with fresh ACL rupture during the previous 4 weeks. The International
      Knee Documentation Committee (IKDC) 2000 score was measured before, immediately
      after, and 3 months after treatment, and 1 year later; magnetic resonance imaging
      (MRI) data were taken before treatment and 1 year after treatment. RESULTS: Both
      groups were comparable at baseline. A repeated measures analysis of variance
      showed a strong effect of time (p < 0.0001; partial eta2 = 0.81) and no
      significant interaction or group effect. Both groups reached near full function
      after 1 year. The IKDC score was 90.9 (standard deviation (SD) 6.7; 95%
      confidence interval (CI) 86.2-95.6) for the RegentK group and 93.3 (SD 3.1; 95%
      CI 91.1-95.5) for the MMT group. CONCLUSION: One treatment session of enhanced
      MMT physiotherapy or RegentK can lead to nearly full function and thus recovery
      of a ruptured ACL after 1 year.

PMID- 29166637
TI  - Assessing Vessel Tone during Coronary Artery Spasm by Dual-Acquisition
      Multidetector Computed Tomography Angiography.
AB  - BACKGROUND: Diminished vascular tone is an established biomarker of heart damage.
      Little is known about the extent of coronary vessel tone (CVT) with spasm as
      assessed by dual-acquisition multidetector computed tomography angiography (MCTA)
      in patients with vasospastic angina (VSA). OBJECTIVE: We evaluated the CVT
      modulated by intravenous nitrate injection (INI) using MCTA imaging in VSA
      patients. METHODS: Twenty-one VSA patients (60 +/- 9 years; 76% males) who
      underwent initial MCTA (without morning vasodilation), followed by an
      intracoronary ergonovine provocation test were included. Within 3 days after the
      initial MCTA patients received INI followed by 28-vessel segment spasm analyzed
      by MCTA 3D software, applying the following formula as the definition of CVT
      index (CVTI): (CSAIV nitrate - CSAinitial/CSAIV nitrate) *100 %, where CSA is the
      cross-sectional area. RESULTS: Compared to the initial MCTA measures, the INI
      provocation resulted in the significant increase of average diameter and CSA at
      the spasm site (2.60 mm [2.11-3.16] vs. 1.42 mm [1.13-2.13]; 5.37 mm2 [3.67-7.54]
      vs. 1.62 mm2 [1.02-3.02]; p < 0.001). The CVTI at the spastic segments was higher
      than at the proximal reference segments (41.0% [21.8-52.3] vs. 18.8% [5.9-26.6]
      for CVTI diameter; 65.1% [38.6-77.0] vs. 33.9% [5.2-48.1] for CVTI CSA,
      respectively). To predict VSA, the cut-off value for CVTI diameter was 38.6% (AUC
      0.777; 95% CI 0.653-0.901) and 62.5% (AUC 0.779; 95% CI 0.657-0.902) for CVTI CSA
      in a receiver-operating characteristic curve analysis, with 57.1% sensitivity and
      92.9% specificity. CONCLUSIONS: This novel imaging technique for assessing CVT by
      dual-acquisition MCTA after applying INI provocation is suitable for the
      detection of coronary artery spasm in patients with VSA.

PMID- 29166638
TI  - Predictors of Surgical Outcomes of Traumatic Peripheral Nerve Injuries in
      Children: An Institutional Experience.
AB  - AIM: This study was undertaken to address the epidemiological characteristics,
      operative details, and surgical outcome of peripheral nerve injuries in children
      treated in a tertiary hospital in India (NIMHANS, Bangalore). MATERIALS AND
      METHODS: This is a retrospective study of epidemiology, operative findings, and
      surgical outcomes over the period of 2000-2016. Our series includes 102 children
      with peripheral nerve injuries of various causes. RESULTS: Intramuscular
      injections were the most common cause (52.9%), followed by entrapment (15.6%).
      The most common nerve involved was the sciatic nerve (54.9%), followed by the
      common peroneal nerve (13.7%), the ulnar nerve (10.8%), and the radial nerve
      (10.8%). Perineural adhesion was the most common intraoperative finding (74.5%),
      followed by a neuroma in continuity (14.7%) and gap (10.8%). Most of the children
      with peripheral adhesion underwent external and internal neurolysis (75.5%).
      Follow-up was available for 67 children. The median follow-up period was 7 months
      (range 3-36). The outcome was assessed according to MRC grading. Favorable
      functional improvement was noted in 76.1% of the children. Age less than 10 years
      (p = 0. 06), injury before 6 months (p = 0.03), and MRC motor grade (<3) (p = 0.
      01) were positive predictive factors related to the final outcome. CONCLUSION:
      Early surgical intervention, age less than 10 years, and incomplete motor palsy
      were the best predictors of a superior functional outcome. This study can serve
      as a guide to determine the epidemiology, duration of intervention, and surgical
      outcome of traumatic peripheral nerve injuries in the pediatric population.

PMID- 29166639
TI  - APOBEC3A Expression in Penile Squamous Cell Carcinoma.
AB  - BACKGROUND: APOBECs (apolipoprotein B mRNA-editing catalytic polypeptides) are
      cytidine deaminases that have been implicated in the host defense against viruses
      by blocking viral replication. They have also been shown to play a role in genome
      hypermutation in several human cancers. An APOBEC3 hypermutation signature has
      been discovered in cervical cancer, which is intimately associated with infection
      by high-risk human papillomaviruses (HPVs). At the same time, HPV genomes
      themselves are subject to DNA editing by APOBECs. Similar to cervical cancer, a
      proportion of penile squamous cell carcinomas (SCCs) is etiologically driven by
      high-risk HPVs, but very little is known about the role of APOBECs in penile SCC
      development and progression. METHODS: A series of 34 penile SCCs was analyzed for
      the expression of APOBEC3A protein by immunohistochemistry. HPV genotyping was
      carried out using a bead-based multiplex hybridization assay preceded by BSGP5+6+
      primer-based amplification. RESULTS: We found a frequent reduction of APOBEC3A
      protein expression in the invasive parts of the majority of HPV-negative penile
      SCCs. In contrast, the majority of HPV-positive penile SCCs retained APOBEC3A
      expression during malignant progression. CONCLUSION: Our results suggest that
      APOBEC3A expression is downregulated during progression towards invasiveness in
      HPV-negative penile SCC, but maintained in HPV-positive penile SCC. How high-risk
      HPV-infected tumor cells tolerate high APOBEC3A, which appears to exert tumor
      suppressive functions in HPV-negative penile SCCs, remains to be elucidated.

PMID- 29166640
TI  - Lactic Acid Bacteria from Andean Grain Amaranth: A Source of Vitamins and
      Functional Value Enzymes.
AB  - Amaranth is a rediscovered pseudocereal with high nutritional properties. Lactic
      acid fermentation can increase the functional and nutritional value of foods. The
      aims of this study were to isolate and evaluate the functionality of lactic acid
      bacteria (LAB) from amaranth. LAB strains (n = 29) isolated from amaranth
      sourdough and grains included Lactobacillus (L.) plantarum (n = 8), L. rhamnosus
      (n = 6), Enterococcus (E.) mundtii (n = 4), E. hermanniensis (n = 3), E. durans
      (n = 1), Enterococcus sp. (n = 1), Leuconostoc (Lc.) mesenteroides (n = 3), and
      Lc. mesenteroides subsp. mesenteroides (n = 3). Only 21% of the strains showed
      the ability to synthesize capsular exopolysaccharides or display ropiness and
      only 8 strains showed amylolytic activity. L. plantarum CRL 2106 and E. durans
      CRL 2122 showed the highest phytase activity, which is of importance for mineral
      bioavailability. L. plantarum CRL 2106 and CRL 2107 and Lc. mesenteroides subsp.
      mesenteroides CRL 2131 synthesized the highest concentrations of B2 and B9
      vitamin (140-250 ng/mL). This study demonstrates the potential of LAB to improve
      the nutritional and functional values of pseudocereal-derived foods.

PMID- 29166641
TI  - Agrowastes as Feedstock for the Production of Endo-beta-Xylanase from Cohnella
      sp. Strain AR92.
AB  - Members of Cohnella sp. isolated from a variety of environments have been shown
      to be glycoside hydrolase producers. Nevertheless, most evaluations of members of
      this genus are limited to their taxonomic description. The strain AR92,
      previously identified as belonging to the genus Cohnella, formed a well-supported
      cluster with C. thailandensis and C. formosensis (>80% bootstrap confidence). Its
      growth and xylanase production were approached by using a mineral-based medium
      containing alkali-pretreated sugarcane bagasse as the main carbon source, which
      was assayed as a convenient source to produce biocatalysts potentially fitting
      its degradation. By means of a two-step statistical approach, the production of
      endoxylanase was moderately improved (20%). However, a far more significant
      improvement was observed (145%), by increasing the inoculum size and lowering the
      fermentation temperature to 25 degrees C, which is below the optimal growth
      temperature of the strain AR92 (37 degrees C). The xylanolytic preparation
      produced by Cohnella sp. AR92 contained mild temperature-active endoxylanase
      (identified as redundant GH10 family) for the main activity which resulted in
      xylobiose and xylo-oligosaccharides as the main products from birchwood xylan.

PMID- 29166642
TI  - Effect of Calcium-Infiltrated Hydroxyapatite Scaffolds on the Hematopoietic Fate
      of Human Umbilical Vein Endothelial Cells.
AB  - Foamed hydroxyapatite offers a three-dimensional scaffold for the development of
      bone constructs, mimicking perfectly the in vivo bone structure. In vivo, calcium
      release at the surface is assumed to provide a locally increased gradient
      supporting the maintenance of the hematopoietic stem cells niche. We fabricated
      hydroxyapatite scaffolds with high surface calcium concentration by infiltration,
      and used human umbilical vein endothelial cells (HUVECs) as a model to study the
      effects on hematopoietic lineage direction. HUVECs are umbilical vein-derived and
      thus possess progenitor characteristics, with a prospective potential to give
      rise to hematopoietic lineages. HUVECs were cultured for long term on three
      dimensional porous hydroxyapatite scaffolds, which were either infiltrated
      biphasic foams or untreated. Controls were cultured in two-dimensional dishes.
      The release of calcium into culture medium was determined, and cells were
      analyzed for typical hematopoietic and endothelial gene expressions, surface
      markers by flow cytometry, and hematopoietic potential using colony-forming unit
      assays. Our results indicate that the biphasic foams promoted a hematopoietic
      lineage direction of HUVECs, suggesting an improved in vivo-like scaffold for
      hematopoietic bone tissue engineering.

PMID- 29166643
TI  - Effects of L- and N-Type Ca Channel Blocker Cilnidipine on Changes in Heart Rate
      and QT Interval During Dialysis.
AB  - BACKGROUND/AIMS: Hemodialysis patients have poor prognosis due to increased
      prevalence of cardiovascular diseases. Treatment to suppress increases in
      sympathetic nerve activity and QT prolongation may have the potential to reduce
      the occurrence of these events. The L/N-type Calcium (Ca) channel blocker
      cilnidipine has unique inhibitory action to inhibit sympathetic nerve activity
      and in a canine model ameliorates QT prolongation. In this study, we investigated
      whether cilnidipine has inhibitory effects on heart rate, an index of sympathetic
      nerve activity, and QT prolongation in patients undergoing dialysis. METHODS: An
      L-type Ca channel blocker amlodipine was administered for 4 weeks followed by
      cilnidipine treatment for 4 weeks. On the last day of each period, heart rate and
      corrected QT interval were estimated and compared between the two periods.
      RESULTS: Cilnidipine showed greater suppression of heart rate during dialysis
      than did amlodipine. The corrected QT interval in one dialysis session was
      significantly increased, and 3 of 17 patients showed prominent QT prolongation
      during administration of amlodipine but not cilnidipine. CONCLUSION: These data
      suggested that cilnidipine may inhibit increases in heart rate and QT interval.
      Cilnidipine may have beneficial effects in reducing cardiovascular events,
      resulting from increased sympathetic nerve activity and lethal arrhythmias in
      hemodialysis patients.

PMID- 29166644
TI  - Cylindromatosis (CYLD), a Deubiquitinase, Attenuates Inflammatory Signaling
      Pathways by Activating Toll-Like Receptor 3 in Human Mesangial Cells.
AB  - BACKGROUND/AIMS: Cylindromatosis (CYLD), a deubiquitinase, negatively regulates
      nuclear factor-kappaB in various cells. However, its potential roles in
      glomerular inflammation remain unclear. Because the activation of the Toll-like
      receptor 3 (TLR3)/type I interferon (IFN) pathways plays a pivotal role in
      chronic kidney diseases (CKD), we examined the role of CYLD in the TLR3 signaling
      in cultured human mesangial cells (MCs). METHODS: We stimulated CYLD-silenced MCs
      with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of dsRNA,
      and studied representative TLR3/IFN-beta pathways (i.e., TLR3/IFN-beta/retinoic
      acid-inducible gene-I (RIG-I)/CCL5, and TLR3/IFN-beta/melanoma differentiation
      associated gene 5 (MDA5)/CXCL10 axes) using RT-PCR, western blotting, and ELISA.
      We also used immunofluorescence staining and microscopy to examine mesangial CYLD
      expression in biopsied specimens from patients with CKD. RESULTS: CYLD silencing
      resulted in an increase of poly IC-induced RIG-I and MDA5 protein levels and
      increased CCL5 and CXCL10 mRNA and protein expression, but unexpectedly decreased
      mRNA expressions of RIG-I and MDA5. Interestingly, CYLD silencing did not affect
      IFN-beta or the phosphorylated STAT1 (signal transducers and activator of
      transcription protein 1). CYLD was highly expressed in biopsied specimens from
      patients with proliferative lupus nephritis (LN). CONCLUSION: CYLD inhibits post
      transcriptional regulation of RIG-I and MDA5 expression following TLR3 activation
      in MCs. CYLD may be involved in the pathogenesis of CKD, especially pathogenesis
      of LN.

PMID- 29166646
TI  - Reconstruction of membrane current by deconvolution and its application to
      membrane capacitance measurements in cardiac myocytes.
AB  - Correct detection of membrane currents under whole-cell patch-clamp conditions is
      limited by the transfer function of a recording system. The low-pass output
      filter of a recording amplifier alters the time course of membrane current and
      causes errors in relevant descriptors. To solve these problems, we developed a
      practical procedure for reconstruction of the time course of membrane currents
      based on deconvolution of recorded currents in frequency domain. The procedure
      was tested on membrane capacitance estimates from current responses to step
      voltage pulses. The reconstructed current responses, in contrast to original
      current records, could be described exactly by an adequate impedance model of a
      recorded cell. The reconstruction allowed to increase the accuracy and
      reliability of membrane capacitance measurements in wide range of cell sizes and
      to suppress the cross-talk errors well below the noise. Moreover, it allowed
      resolving the instabilities in recording conditions arising from parasitic
      capacitance and seal resistance variation. Complex tests on hardware models, on
      simulated data sets, and on living cells confirmed robustness and reliability of
      the deconvolution procedure. The aptitude of the method was demonstrated in
      isolated rat cardiac myocytes by recording of spontaneous vesicular events, by
      discerning the formation of a fusion pore, and by revealing artefacts due to
      unstable seal resistance.

PMID- 29166645
TI  - Angiotensin II Infusion Does Not Cause Abdominal Aortic Aneurysms in
      Apolipoprotein E-Deficient Rats.
AB  - The apolipoprotein E-deficient (apoE-/-) mouse model has advanced our
      understanding of cardiovascular disease mechanisms and experimental therapeutics.
      This spontaneous model recapitulates aspects of human atherosclerosis, and allows
      for the development of dissecting abdominal aortic aneurysms (AAAs) when combined
      with angiotensin II. We characterized apoE-/- rats and hypothesized that, similar
      to mice, they would develop dissecting AAAs. We created rats with a 16-bp
      deletion of the apoE gene using transcription activator-like effector nucleases.
      We imaged the suprarenal aorta for 28 days after implantation of miniosmotic
      pumps that infuse angiotensin II (AngII, 200 ng/kg/min). Blood pressure (BP),
      serum lipids and lipoproteins, and histology were also analyzed. These rats did
      not develop pathological aortic dissection, but we did observe a decrease in
      circumferential cyclic strain, a rise in BP, and microstructural changes in the
      aortic medial layer. We also measured increased serum lipids with and without
      administration of a high-fat diet, but did not detect atherosclerotic plaques.
      Chronic infusion of AngII did not lead to the formation of dissecting AAAs or
      atherosclerosis in the rats used in this study. While reduced amounts of
      atherosclerosis may explain this resistance to dissecting aneurysms, further
      investigation is needed to fully characterize species-specific differences.

PMID- 29166647
TI  - The reciprocal relations between experiential avoidance, school stressor, and
      psychological stress response among Japanese adolescents.
AB  - The present study aimed to investigate the reciprocal relations between
      experiential avoidance, stressor, and psychological stress response (which
      consist of anger, depression, anxiety, helplessness, and physical complaints). In
      this study, 688 Japanese junior high school students (353 boys, 334 girls, 1
      unidentified; mean age 13.28 years) completed three waves of questionnaires on
      experiential avoidance, stressor, and psychological stress response, with one
      week intervals between measurement waves. Results from cross-lagged panel
      analyses showed that experiential avoidance predicted subsequent stressor and
      psychological stress response. Furthermore, the stressor and psychological stress
      response influenced by prior experiential avoidance affected subsequent
      occurrence of experiential avoidance. The findings suggest that reciprocal
      relations exist among the variables, and that the interaction between
      experiential avoidance and psychological stress was possible in adolescents.

PMID- 29166648
TI  - Different response to hypoxia of adipose-derived multipotent cells from obese
      subjects with and without metabolic syndrome.
AB  - BACKGROUND/OBJECTIVES: Multiple studies suggest that hypoxia, together with
      inflammation, could be one of the phenomena involved in the onset and progression
      of obesity-related insulin resistance. In addition, dysfunction of adipose tissue
      in obese subjects with metabolic syndrome is associated with decreased
      angiogenesis. However, some subjects with a high body mass index do not develop
      metabolic abnormalities associated with obesity. The aim of the current study was
      to examine the neovascular properties of visceral adipose tissue-derived
      multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs) from normal
      weight subjects (Nw) and obese patients with metabolic syndrome (MS) and without
      metabolic syndrome (NonMS). METHODS: This was a 2-year study to enroll subjects
      who underwent bariatric surgery or cholecystectomy. Eight patients who underwent
      either bariatric surgery or cholecystectomy (27 patients) participated in the
      study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were
      processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were
      characterized by tubule formation assay, ELISA, flow cytometry, migration rate,
      and qRT-PCR, and the effects of visASCs-conditioned medium on survival and
      endothelial cell tubule formation were evaluated. RESULTS: Hypox-visASCs from
      NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs
      from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+
      cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was
      accompanied not only by a lower migration rate from the chemotactic effects of
      stromal cell derived factor 1alpha, but also by lower levels of NOX5 mRNA
      expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed
      by hypox-visASCs correlated positively with the body mass index and waist
      circumference of the subjects, the concentration of vascular endothelial growth
      factor present in hypox-visASC-conditioned culture medium decreased significantly
      with increasing plasma glucose. The survival rate and tubules formed by
      endothelial cells cultured in hypox-visASC-conditioned medium decreased
      significantly with increasing homeostasis model assessment to quantify insulin
      resistance. CONCLUSIONS: Our results suggest that hypox-visASCs from NonMS
      subjects could promote healthy adipose tissue expansion, while hypox-visASCs from
      MS subjects appear to contribute to the decreased angiogenic potential and
      increased inflammation underlying adipose tissue dysfunction in obesity. Our
      results emphasize the importance of taking into account not only the BMI but also
      the metabolic profile of the subjects during the implementation of ASCs-based
      therapy to promote neovascularization.

PMID- 29166649
TI  - Extended light exposure increases stem digestibility and biomass production of
      switchgrass.
AB  - Switchgrass is a photoperiod-sensitive energy grass suitable for growing in the
      marginal lands of China. We explored the effects of extended photoperiods of low
      irradiance light (7 MUmol.m-2.s-1, no effective photosynthesis) on the growth,
      the biomass dry weight, the biomass allocation, and, especially, the stem
      digestibility and cell wall characteristics of switchgrass. Two extended
      photoperiods (i.e., 18 and 24 h) were applied over Alamo. Extended light exposure
      (18 and 24 h) resulted in delayed heading and higher dry weights of vegetative
      organs (by 32.87 and 35.94%, respectively) at the expense of reducing the amount
      of sexual organs (by 40.05 and 50.87%, respectively). Compared to the control
      group (i.e., natural photoperiod), the yield of hexoses (% dry matter) in the
      stems after a direct enzymatic hydrolysis (DEH) treatment significantly increased
      (by 44.02 and 46.10%) for those groups irradiated during 18 and 24 h,
      respectively. Moreover, the yield of hexoses obtained via enzymatic hydrolysis
      increased after both basic (1% NaOH) and acid (1% H2SO4) pretreatments for the
      groups irradiated during 18 and 24 h. Additionally, low-irradiance light
      extension (LILE) significantly increased the content of non-structural
      carbohydrates (NSCs) while notably reducing the lignin content and the syringyl
      to guaiacyl (S/G) ratio. These structural changes were in part responsible for
      the observed improved stem digestibility. Remarkably, LILE significantly
      decreased the cellulose crystallinity index (CrI) of switchgrass by significantly
      increasing both the arabinose substitution degree in xylan and the content of
      ammonium oxalate-extractable uronic acids, both favoring cellulose digestibility.
      Despite this LILE technology is not applied to the cultivation of switchgrass on
      a large scale yet, we believe that the present work is important in that it
      reveals important relationships between extended day length irradiations and
      biomass production and quality. Additionally, this study paves the way for
      improving biomass production and digestibility via genetic modification of day
      length sensitive transcription factors or key structural genes in switchgrass
      leaves.

PMID- 29166650
TI  - Feeding-induced changes in allatostatin-A and short neuropeptide F in the
      antennal lobes affect odor-mediated host seeking in the yellow fever mosquito,
      Aedes aegypti.
AB  - Aedes aegypti is a model species in which the endogenous regulation of odor
      mediated host seeking behavior has received some attention. Sugar feeding and
      host seeking in female A. aegypti are transiently inhibited following a blood
      meal. This inhibition is partially mediated by short neuropeptide F (sNPF). The
      paired antennal lobes (ALs), as the first processing centers for olfactory
      information, has been shown to play a significant role in the neuropeptidergic
      regulation of odor-mediated behaviors in insects. The expression of sNPF, along
      with other peptides in the ALs of A. aegypti, indicate parallel neuromodulatory
      systems that may affect olfactory processing. To identify neuropeptides involved
      in regulating the odor-mediated host seeking behavior in A. aegypti, we use a
      semi-quantitative neuropeptidomic analysis of single ALs to analyze changes in
      the levels of five individual neuropeptides in response to different feeding
      regimes. Our results show that the level of sNPF-2, allatostatin-A-5 (AstA-5) and
      neuropeptide-like precursor-1-5 (NPLP-1-5), but not of tachykinin-related
      peptides and SIFamide (SIFa), in the AL of female mosquitoes, changes 24 h and 48
      h post-blood meal, and are dependent on prior access to sugar. To assess the role
      of these neuropeptides in modulating host seeking behavior, when systemically
      injected individually, sNPF-2 and AstA-5 significantly reduced host seeking
      behavior. However, only the injection of the binary mixture of the two
      neuropeptides lead to a host seeking inhibition similar to that observed in blood
      fed females. We conclude that modulation of the odor mediated host seeking
      behavior of A. aegypti is likely regulated by a dual neuropeptidergic pathway
      acting in concert in the ALs.

PMID- 29166652
TI  - Do patients' faces influence General Practitioners' cancer suspicions? A test of
      automatic processing of sociodemographic information.
AB  - BACKGROUND: Delayed cancer diagnosis leads to poorer patient outcomes. During
      short consultations, General Practitioners (GPs) make quick decisions about
      likelihood of cancer. Patients' facial cues are processed rapidly and may
      influence diagnosis. AIM: To investigate whether patients' facial characteristics
      influence immediate perception of cancer risk by GPs. DESIGN AND SETTING: Web
      based binary forced choice experiment with GPs from Northeast Scotland. METHOD:
      GPs were presented with a series of pairs of face prototypes and asked to quickly
      select the patient more likely to have cancer. Faces were modified with respect
      to age, gender, and ethnicity. Choices were analysed using Chi-squared goodness
      of-fit statistics with Bonferroni corrections. RESULTS: Eighty-two GPs
      participated. GPs were significantly more likely to suspect cancer in older
      patients. Gender influenced GP cancer suspicion, but this was modified by age:
      the male face was chosen as more likely to have cancer than the female face for
      young (72% of GPs;95% CI 61.0-87.0) and middle-aged faces (65.9%; 95% CI 54.7
      75.5); but 63.4% (95% CI 52.2-73.3) decided the older female was more likely to
      have cancer than the older male (p = 0.015). GPs were significantly more likely
      to suspect cancer in the young Caucasian male (65.9% (95% CI 54.7, 75.5))
      compared to the young Asian male (p = 0.004). CONCLUSION: GPs' first impressions
      about cancer risk are influenced by patient age, gender, and ethnicity. Tackling
      GP cognitive biases could be a promising way of reducing cancer diagnostic
      delays, particularly for younger patients.

PMID- 29166651
TI  - Stiffness analysis of 3D spheroids using microtweezers.
AB  - We describe a novel mechanical characterization method that has directly measured
      the stiffness of cancer spheroids for the first time to our knowledge. Stiffness
      is known to be a key parameter that characterizes cancerous and normal cells.
      Atomic force microscopy or optical tweezers have been typically used for
      characterization of single cells with the measurable forces ranging from sub pN
      to a few hundred nN, which are not suitable for measurement of larger 3D cellular
      structures such as spheroids, whose mechanical characteristics have not been
      fully studied. Here, we developed microtweezers that measure forces from sub
      hundred nN to mN. The wide force range was achieved by the use of replaceable
      cantilevers fabricated from SU8, and brass. The chopstick-like motion of the two
      cantilevers facilitates easy handling of samples and microscopic observation for
      mechanical characterization. The cantilever bending was optically tracked to find
      the applied force and sample stiffness. The efficacy of the method was
      demonstrated through stiffness measurement of agarose pillars with known
      concentrations. Following the initial system evaluation with agarose, two
      cancerous (T47D and BT474) and one normal epithelial (MCF 10A) breast cell lines
      were used to conduct multi-cellular spheroid measurements to find Young's moduli
      of 230, 420 and 1250 Pa for BT474, T47D, and MCF 10A, respectively. The results
      showed that BT474 and T47D spheroids are six and three times softer than
      epithelial MCF10A spheroids, respectively. Our method successfully characterized
      samples with wide range of Young's modulus including agarose (25-100 kPa),
      spheroids of cancerous and non-malignant cells (190-200 MUm, 230-1250 Pa) and
      collagenase-treated spheroids (215 MUm, 130 Pa).

PMID- 29166653
TI  - Testing the applicability of a benthic foraminiferal-based transfer function for
      the reconstruction of paleowater depth changes in Rhodes (Greece) during the
      early Pleistocene.
AB  - We present paleo-water depth reconstructions for the Pefka E section deposited on
      the island of Rhodes (Greece) during the early Pleistocene. For these
      reconstructions, a transfer function (TF) using modern benthic foraminifera
      surface samples from the Adriatic and Western Mediterranean Seas has been
      developed. The TF model gives an overall predictive accuracy of ~50 m over a
      water depth range of ~1200 m. Two separate TF models for shallower and deeper
      water depth ranges indicate a good predictive accuracy of 9 m for shallower water
      depths (0-200 m) but far less accuracy of 130 m for deeper water depths (200-1200
      m) due to uneven sampling along the water depth gradient. To test the robustness
      of the TF, we randomly selected modern samples to develop random TFs, showing
      that the model is robust for water depths between 20 and 850 m while greater
      water depths are underestimated. We applied the TF to the Pefka E fossil data
      set. The goodness-of-fit statistics showed that most fossil samples have a poor
      to extremely poor fit to water depth. We interpret this as a consequence of a
      lack of modern analogues for the fossil samples and removed all samples with
      extremely poor fit. To test the robustness and significance of the
      reconstructions, we compared them to reconstructions from an alternative TF model
      based on the modern analogue technique and applied the randomization TF test. We
      found our estimates to be robust and significant at the 95% confidence level, but
      we also observed that our estimates are strongly overprinted by orbital,
      precession-driven changes in paleo-productivity and corrected our estimates by
      filtering out the precession-related component. We compared our corrected record
      to reconstructions based on a modified plankton/benthos (P/B) ratio, excluding
      infaunal species, and to stable oxygen isotope data from the same section, as
      well as to paleo-water depth estimates for the Lindos Bay Formation of other
      sediment sections of Rhodes. These comparisons indicate that our orbital
      corrected reconstructions are reasonable and reflect major tectonic movements of
      Rhodes during the early Pleistocene.

PMID- 29166654
TI  - Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques.
AB  - BACKGROUND: There are currently no licensed vaccines available for prevention of
      botulism in humans. The vaccination is not desirable due to expanding therapeutic
      indications of botulinum toxins. The only available specific treatment for
      botulism is antitoxin to remove circulating toxin, thus, preventing further
      neuronal damage. BAT(r) (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)
      (Equine)) has been developed and its therapeutic efficacy evaluated against
      botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques. METHODS AND
      FINDINGS: In a post-exposure prophylaxis (PEP) study, animals were exposed to 4x
      LD50/kg of BoNT/A and administered intravenously with either BAT (1x or 0.1x
      scaled human dose), or placebo at 4 hours post-exposure. The animals were
      monitored for 14 days. For the therapeutic intervention studies, animals were
      exposed to a 1.7x LD50/kg of BoNT/A and treated intravenously with either placebo
      or BAT at a 1x scaled human dose at the onset of clinical signs. Animals were
      monitored on an hourly basis for 14 or 21 days. In the PEP study, all animals
      tolerated equine based antitoxin without any adverse clinical signs. A 100%
      survival was observed in groups treated with the BAT compared to 0% survival in
      those treated with the placebo (p<0.001, Fisher's exact test). BAT antitoxin
      prevented the development of signs of neurotoxicity of botulinum toxin. In a
      therapeutic study, treatment with the BAT at scaled 1x human dose after the onset
      of clinical signs significantly enhanced survival compared to the placebo (46.6%
      vs. 0%, p<0.0001, Fisher's exact test). Additionally, treatment with the BAT
      delayed the progression of signs (muscular weakness, respiratory distress,
      oral/nasal discharge) of toxin intoxication and reduced the severity of the
      disease. CONCLUSIONS: A single dose of BAT, when administered to symptomatic
      monkeys, resulted in a statistically significant survival benefit compared to the
      placebo. Additionally, BAT completely protected monkeys from the clinical signs
      of intoxication and subsequent death when administered as PEP treatment. These
      data in part supported the licensure of BAT under the Animal Rule in the United
      States by the Food and Drug Administration.

PMID- 29166655
TI  - How well do you know your mutation? Complex effects of genetic background on
      expressivity, complementation, and ordering of allelic effects.
AB  - For a given gene, different mutations influence organismal phenotypes to varying
      degrees. However, the expressivity of these variants not only depends on the DNA
      lesion associated with the mutation, but also on factors including the genetic
      background and rearing environment. The degree to which these factors influence
      related alleles, genes, or pathways similarly, and whether similar developmental
      mechanisms underlie variation in the expressivity of a single allele across
      conditions and among alleles is poorly understood. Besides their fundamental
      biological significance, these questions have important implications for the
      interpretation of functional genetic analyses, for example, if these factors
      alter the ordering of allelic series or patterns of complementation. We examined
      the impact of genetic background and rearing environment for a series of
      mutations spanning the range of phenotypic effects for both the scalloped and
      vestigial genes, which influence wing development in Drosophila melanogaster.
      Genetic background and rearing environment influenced the phenotypic outcome of
      mutations, including intra-genic interactions, particularly for mutations of
      moderate expressivity. We examined whether cellular correlates (such as cell
      proliferation during development) of these phenotypic effects matched the
      observed phenotypic outcome. While cell proliferation decreased with mutations of
      increasingly severe effects, surprisingly it did not co-vary strongly with the
      degree of background dependence. We discuss these findings and propose a
      phenomenological model to aid in understanding the biology of genes, and how this
      influences our interpretation of allelic effects in genetic analysis.

PMID- 29166656
TI  - Fragmentation modes and the evolution of life cycles.
AB  - Reproduction is a defining feature of living systems. To reproduce, aggregates of
      biological units (e.g., multicellular organisms or colonial bacteria) must
      fragment into smaller parts. Fragmentation modes in nature range from binary
      fission in bacteria to collective-level fragmentation and the production of
      unicellular propagules in multicellular organisms. Despite this apparent
      ubiquity, the adaptive significance of fragmentation modes has received little
      attention. Here, we develop a model in which groups arise from the division of
      single cells that do not separate but stay together until the moment of group
      fragmentation. We allow for all possible fragmentation patterns and calculate the
      population growth rate of each associated life cycle. Fragmentation modes that
      maximise growth rate comprise a restrictive set of patterns that include
      production of unicellular propagules and division into two similar size groups.
      Life cycles marked by single-cell bottlenecks maximise population growth rate
      under a wide range of conditions. This surprising result offers a new
      evolutionary explanation for the widespread occurrence of this mode of
      reproduction. All in all, our model provides a framework for exploring the
      adaptive significance of fragmentation modes and their associated life cycles.

PMID- 29166657
TI  - The effects of Kinesio Taping on the trajectory of the forelimb and the muscle
      activity of the Musculus brachiocephalicus and the Musculus extensor carpi
      radialis in horses.
AB  - BACKGROUND INFORMATION: The present study aimed to investigate the effects of
      Kinesio Taping on the trajectory of the forelimb and the muscle activity of the
      M. brachiocephalicus and the M. extensor carpi radialis in horses. 19 horses and
      ponies of different breeds (body weight: 496+/-117 kg), gender (8 mares, 10
      geldings and 3 stallions) and ages (14.9+/-6.9 years old) were analysed without
      Kinesio Tape ("no tape"), with Kinesio Tape (muscle facilitation application on
      both muscles of both sides, "with tape") and immediately after Kinesio Taping
      ("post tape") through kinematic motion analysis and surface electromyography on a
      treadmill at the walk (speed: 1.5+/-0.1 m/s) and trot (speed: 3.1+/-0.3 m/s).
      RESULTS: The results of the surface electromyography (maximum muscle activity at
      the walk and trot) and the kinematic motion analysis (maximum stride length and
      maximum height of the forelimbs flight arc at the walk and trot) showed that
      there were no significant differences between "no tape", "with tape" and "post
      tape". CONCLUSION: To sum up, Kinesio Taping on the M. brachiocephalicus and the
      M. extensor carpi radialis does not affect (in a positive or negative manner) the
      trajectory of the forelimb or the muscle activity of the M. brachiocephalicus and
      the M. extensor carpi radialis in horses.

PMID- 29166658
TI  - Episodic future thinking reduces temporal discounting in healthy adolescents.
AB  - Episodic Future Thinking has proven efficient in reducing impulsive behavior in
      several adult populations. Whether it also has a beneficial impact on decision
      making in adolescents is not known. Here the impact of episodic future thinking
      on discounting behavior was investigated in a sample of healthy adolescents (n =
      44, age range 13-16 years). Discounting behavior in trials including episodic
      future thinking was significantly less impulsive than in control trials (t =
      2.74, p = .009, dz = .44). In a subsample we controlled for executive function,
      alcohol use and developmental measures. Neither executive function nor alcohol
      use but developmental measures explained variability in the effect of episodic
      future thinking. These findings reveal that episodic future thinking can improve
      adolescent decision making while the effect is to some degree modulated by
      developmental measures.

PMID- 29166659
TI  - Sex-specific influences of mtDNA mitotype and diet on mitochondrial functions and
      physiological traits in Drosophila melanogaster.
AB  - Here we determine the sex-specific influence of mtDNA type (mitotype) and diet on
      mitochondrial functions and physiology in two Drosophila melanogaster lines. In
      many species, males and females differ in aspects of their energy production.
      These sex-specific influences may be caused by differences in evolutionary
      history and physiological functions. We predicted the influence of mtDNA
      mutations should be stronger in males than females as a result of the organelle's
      maternal mode of inheritance in the majority of metazoans. In contrast, we
      predicted the influence of diet would be greater in females due to higher
      metabolic flexibility. We included four diets that differed in their protein:
      carbohydrate (P:C) ratios as they are the two-major energy-yielding
      macronutrients in the fly diet. We assayed four mitochondrial function traits
      (Complex I oxidative phosphorylation, reactive oxygen species production,
      superoxide dismutase activity, and mtDNA copy number) and four physiological
      traits (fecundity, longevity, lipid content, and starvation resistance). Traits
      were assayed at 11 d and 25 d of age. Consistent with predictions we observe that
      the mitotype influenced males more than females supporting the hypothesis of a
      sex-specific selective sieve in the mitochondrial genome caused by the maternal
      inheritance of mitochondria. Also, consistent with predictions, we found that the
      diet influenced females more than males.

PMID- 29166660
TI  - Great apes are sensitive to prior reliability of an informant in a gaze following
      task.
AB  - Social animals frequently rely on information from other individuals. This can be
      costly in case the other individual is mistaken or even deceptive. Human infants
      below 4 years of age show proficiency in their reliance on differently reliable
      informants. They can infer the reliability of an informant from few interactions
      and use that assessment in later interactions with the same informant in a
      different context. To explore whether great apes share that ability, in our study
      we confronted great apes with a reliable or unreliable informant in an object
      choice task, to see whether that would in a subsequent task affect their gaze
      following behaviour in response to the same informant. In our study, prior
      reliability of the informant and habituation during the gaze following task
      affected both great apes' automatic gaze following response and their more
      deliberate response of gaze following behind barriers. As habituation is very
      context specific, it is unlikely that habituation in the reliability task
      affected the gaze following task. Rather it seems that apes employ a reliability
      tracking strategy that results in a general avoidance of additional information
      from an unreliable informant.

PMID- 29166661
TI  - Ultraconserved elements (UCEs) resolve the phylogeny of Australasian smurf
      weevils.
AB  - Weevils (Curculionoidea) comprise one of the most diverse groups of organisms on
      earth. There is hardly a vascular plant or plant part without its own species of
      weevil feeding on it and weevil species diversity is greater than the number of
      fishes, birds, reptiles, amphibians and mammals combined. Here, we employ
      ultraconserved elements (UCEs) designed for beetles and a novel partitioning
      strategy of loci to help resolve phylogenetic relationships within the radiation
      of Australasian smurf-weevils (Eupholini). Despite being emblematic of the New
      Guinea fauna, no previous phylogenetic studies have been conducted on the
      Eupholini. In addition to a comprehensive collection of fresh specimens, we
      supplement our taxon sampling with museum specimens, and this study is the first
      target enrichment phylogenomic dataset incorporating beetle specimens from museum
      collections. We use both concatenated and species tree analyses to examine the
      relationships and taxonomy of this group. For species tree analyses we present a
      novel partitioning strategy to better model the molecular evolutionary process in
      UCEs. We found that the current taxonomy is problematic, largely grouping species
      on the basis of similar color patterns. Finally, our results show that most loci
      required multiple partitions for nucleotide rate substitution, suggesting that
      single partitions may not be the optimal partitioning strategy to accommodate
      rate heterogeneity for UCE loci.

PMID- 29166662
TI  - Detection of HBsAg mutants in the blood donor population of Pakistan.
AB  - BACKGROUND: Infection with the Hepatitis B virus (HBV) continues to be one of the
      leading healthcare issues in Pakistan, affecting over 6 million people. The
      existence of HBsAg mutants is well documented in many countries. In Pakistan, HBV
      screening in the majority of the blood banks is performed by Rapid Detection
      Devices or ELISA tests. These tests are designed to detect HBsAg, but may not
      detect the mutant HBsAg. Failure to detect the HBsAg mutant may result in the
      transmission of HBV infection from donor to recipient. Hence, there is a need to
      identify a HBsAg assay which can detect mutants in a country where simple and
      conventional HBsAg assays with varying sensitivity and specificity are used to
      detect HBV infections. MATERIAL AND METHODS: Three routinely used diagnostic
      tests (Rapid Detection Devices, ELISA and CLIA) for HBsAg were compared with the
      LIAISON(r) XL Murex HBsAg Quant Assay to determine the prevalence of HBV mutants
      in the Pakistani blood donor population. The samples of blood donors from
      different cities of Pakistan were collected. The testing was performed using SD
      Bioline rapid assay (n = 1500), ELISA (n = 1500), and Abbott ARCHITECT(r)CLIA
      system (n = 1500) at the centers where the donations were collected. All samples
      (n = 4500) were re-tested for comparative analysis on the LIAISON(r) XL Murex
      HBsAg Quant assay (DiaSorin S.p.A.). PCR testing was performed as a gold standard
      on all discordant samples. RESULTS: 119/4500 (2.64%) of the samples were positive
      for antibodies against HBsAg. The sensitivity of SD Bioline Rapid, GB HBsAg
      ELISA, Abbott ARCHITECT(r) and LIAISON(r) XL Murex HBsAg Quant assay was 17.24%,
      43.75%, 90.91%and 100% respectively. The specificity of SD Bioline Rapid, GB
      HBsAg ELISA, Abbott ARCHITECT(r) and LIAISON(r) XL Murex HBsAg Quant Assay was
      98.82%, 99.59%, 100% and 100%, respectively. CONCLUSION: LIAISON(r) XL Murex
      HBsAg Quant assay is a highly sensitive, specific and accurate screening assay
      for detecting wild type as well as mutant HBsAg.

PMID- 29166663
TI  - A general model for predicting the binding affinity of reversibly and
      irreversibly dimerized ligands.
AB  - Empirical data has shown that bivalent inhibitors can bind a given target protein
      significantly better than their monomeric counterparts. However, predicting the
      corresponding theoretical fold improvements has been challenging. The current
      work builds off the reacted-site probability approach to provide a
      straightforward baseline reference model for predicting fold-improvements in
      effective affinity of dimerized ligands over their monomeric counterparts. For
      the more familiar irreversibly linked bivalents, the model predicts a weak
      dependence on tether length and a scaling of the effective affinity with the 3/2
      power of the monomer's affinity. For the previously untreated case of the
      emerging technology of reversibly linking dimers, the effective affinity is also
      significantly improved over the affinity of the non-dimerizing monomers. The
      model is related back to experimental quantities, such as EC50s, and the
      approaches to fully characterize the system given the assumptions of the model.
      Because of the predicted significant potency gains, both irreversibly and
      reversibly linked bivalent ligands offer the potential to be a disruptive
      technology in pharmaceutical research.

PMID- 29166664
TI  - Is there a reasonable excuse for not providing post-operative analgesia when
      using animal models of peripheral neuropathic pain for research purposes?
AB  - INTRODUCTION: The induction of neuropathic pain-like behaviors in rodents often
      requires surgical intervention. This engages acute nociceptive signaling events
      that contribute to pain and stress post-operatively that from a welfare
      perspective demands peri-operative analgesic treatment. However, a large number
      of researchers avoid providing such care based largely on anecdotal opinions that
      it might interfere with model pathophysiology in the longer term. OBJECTIVES: To
      investigate effects of various peri-operative analgesic regimens encapsulating
      different mechanisms and duration of action, on the development of post-operative
      stress/welfare and pain-like behaviors in the Spared Nerve Injury (SNI)-model of
      neuropathic pain. METHODS: Starting on the day of surgery, male Sprague-Dawley
      rats were administered either vehicle (s.c.), carprofen (5.0mg/kg, s.c.),
      buprenorphine (0.1mg/kg s.c. or 1.0mg/kg p.o. in Nutella(r)),
      lidocaine/bupivacaine mixture (local irrigation) or a combination of all
      analgesics, with coverage from a single administration, and up to 72 hours. Post
      operative stress and recovery were assessed using welfare parameters, bodyweight,
      food-consumption, and fecal corticosterone, and hindpaw mechanical allodynia was
      tested for assessing development of neuropathic pain for 28 days. RESULTS: None
      of the analgesic regimes compromised the development of mechanical allodynia.
      Unexpectedly, the combined treatment with 0.1mg/kg s.c. buprenorphine and
      carprofen for 72 hours and local irrigation with lidocaine/bupivacaine, caused
      severe adverse effects with peritonitis. This was not observed when the
      combination included a lower dose of buprenorphine (0.05mg/kg, s.c.), or when
      buprenorphine was administered alone (0.1mg/kg s.c. or 1.0mg/kg p.o.) for 72
      hours. An elevated rate of wound dehiscence was observed especially in the
      combined treatment groups, underlining the need for balanced analgesia. Repeated
      buprenorphine injections had positive effects on body weight the first day after
      surgery, but depressive effects on food intake and body weight later during the
      first week. CONCLUSION: Post-operative analgesia does not appear to affect
      established neuropathic hypersensitivity outcome in the SNI model.

PMID- 29166665
TI  - Meditation experts try Virtual Reality Mindfulness: A pilot study evaluation of
      the feasibility and acceptability of Virtual Reality to facilitate mindfulness
      practice in people attending a Mindfulness conference.
AB  - Regular mindfulness practice benefits people both mentally and physically, but
      many populations who could benefit do not practice mindfulness. Virtual Reality
      (VR) is a new technology that helps capture participants' attention and gives
      users the illusion of "being there" in the 3D computer generated environment,
      facilitating sense of presence. By limiting distractions from the real world,
      increasing sense of presence and giving people an interesting place to go to
      practice mindfulness, Virtual Reality may facilitate mindfulness practice.
      Traditional Dialectical Behavioral Therapy (DBT(r)) mindfulness skills training
      was specifically designed for clinical treatment of people who have trouble
      focusing attention, however severe patients often show difficulties or lack of
      motivation to practice mindfulness during the training. The present pilot study
      explored whether a sample of mindfulness experts would find useful and recommend
      a new VR Dialectical Behavioral Therapy (DBT(r)) mindfulness skills training
      technique and whether they would show any benefit. Forty four participants
      attending a mindfulness conference put on an Oculus Rift DK2 Virtual Reality
      helmet and floated down a calm 3D computer generated virtual river while
      listening to digitized DBT(r) mindfulness skills training instructions. On
      subjective questionnaires completed by the participants before and after the VR
      DBT(r) mindfulness skills training session, participants reported
      increases/improvements in state of mindfulness, and reductions in negative
      emotional states. After VR, participants reported significantly less sadness,
      anger, and anxiety, and reported being significantly more relaxed. Participants
      reported a moderate to strong illusion of going inside the 3D computer generated
      world (i.e., moderate to high "presence" in VR) and showed high acceptance of VR
      as a technique to practice mindfulness. These results show encouraging
      preliminary evidence of the feasibility and acceptability of using VR to practice
      mindfulness based on clinical expert feedback. VR is a technology with potential
      to increase computerized dissemination of DBT(r) skills training modules. Future
      research is warranted.

PMID- 29166666
TI  - Evaluating the efficacy of an active compression brace on orthostatic
      cardiovascular responses.
AB  - Orthostatic intolerance, one of the principle causes of syncope, can occur
      secondary to concomitant venous pooling and enhanced capillary filtration. We
      aimed to evaluate a prototype portable calf active compression brace (ACB)
      designed to improve orthostatic haemodynamic control. Fourteen healthy volunteers
      participated in a randomized, placebo controlled, cross-over, double-blind study.
      Testing consisted of head-upright tilting and walking on a treadmill conducted on
      two consecutive days with a pair of ACBs wrapped around both calves. The ACB was
      actuated on one test day, but not on the other (placebo). Wearability, comfort,
      and ambulatory use of the ACB were assessed using questionnaires. The average
      calf pressure exerted by the ACB was 46.3+/-2.2 mmHg and the actuation pressure
      was 20.7+/-1.7 mmHg. When considering the differences between ACB actuation and
      placebo during tilt after supine rest there were trends for a larger stroke
      volume (+5.20+/-2.34%, p = 0.05) and lower heart rate (-5.12+/-2.41%, p = 0.06)
      with ACB actuation, with no effect on systolic arterial pressure (+4.86+/-3.41%,
      p = 0.18). The decrease in stroke volume after ten minutes of tilting was
      positively correlated with the height:calf circumference (r = 0.464; p = 0.029; n
      = 22; both conditions combined). The increase in heart rate after ten minutes of
      tilting was negatively correlated with the height:calf circumference (r = -0.485;
      p = 0.022; n = 22; both conditions combined) and was positively correlated with
      the average calf circumference (r = 0.539; p = 0.009; n = 22; both conditions
      combined). Participants reported good ACB wearability and comfort during
      ambulatory use. These data verify that the ACB increased stroke volume during
      tilting in healthy controls. Active calf compression garments may be a viable
      option for the management of orthostatic intolerance.

PMID- 29166668
TI  - Interleukin-36gamma and IL-36 receptor signaling mediate impaired host immunity
      and lung injury in cytotoxic Pseudomonas aeruginosa pulmonary infection: Role of
      prostaglandin E2.
AB  - Pseudomonas aeruginosa is a Gram-negative pathogen that can lead to severe
      infection associated with lung injury and high mortality. The interleukin (IL)-36
      cytokines (IL-36alpha, IL-36beta and IL-36gamma) are newly described IL-1 like
      family cytokines that promote inflammatory response via binding to the IL-36
      receptor (IL-36R). Here we investigated the functional role of IL-36 cytokines in
      the modulating of innate immune response against P. aeruginosa pulmonary
      infection. The intratracheal administration of flagellated cytotoxic P.
      aeruginosa (ATCC 19660) upregulated IL-36alpha and IL-36gamma, but not IL-36beta,
      in the lungs. IL-36alpha and IL-36gamma were expressed in pulmonary macrophages
      (PMs) and alveolar epithelial cells in response to P. aeruginosa in vitro.
      Mortality after bacterial challenge in IL-36 receptor deficient (IL-36R-/-) mice
      and IL-36gamma deficient (IL-36gamma-/-) mice, but not IL-36alpha deficient mice,
      was significantly lower than that of wild type mice. Decreased mortality in IL
      36R-/- mice and IL-36gamma-/- mice was associated with reduction in bacterial
      burden in the alveolar space, bacterial dissemination, production of inflammatory
      cytokines and lung injury, without changes in lung leukocyte influx.
      Interestingly, IL-36gamma enhanced the production of prostaglandin E2 (PGE2)
      during P. aeruginosa infection in vivo and in vitro. Treatment of PMs with
      recombinant IL-36gamma resulted in impaired bacterial killing via PGE2 and its
      receptor; EP2. P. aeruginosa infected EP2 deficient mice or WT mice treated with
      a COX-2-specific inhibitor showed decreased bacterial burden and dissemination,
      but no change in lung injury. Finally, we observed an increase in IL-36gamma, but
      not IL-36alpha, in the airspace and plasma of patients with P. aeruginosa-induced
      acute respiratory distress syndrome. Thus, IL-36gamma and its receptor signal not
      only impaired bacterial clearance in a possible PGE2 dependent fashion but also
      mediated lung injury during P. aeruginosa infection.

PMID- 29166667
TI  - Flotillin scaffold activity contributes to type VII secretion system assembly in
      Staphylococcus aureus.
AB  - Scaffold proteins are ubiquitous chaperones that promote efficient interactions
      between partners of multi-enzymatic protein complexes; although they are well
      studied in eukaryotes, their role in prokaryotic systems is poorly understood.
      Bacterial membranes have functional membrane microdomains (FMM), a structure
      homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts,
      bacterial FMM harbor a scaffold protein termed flotillin that is thought to
      promote interactions between proteins spatially confined to the FMM. Here we used
      biochemical approaches to define the scaffold activity of the flotillin homolog
      FloA of the human pathogen Staphylococcus aureus, using assembly of interacting
      protein partners of the type VII secretion system (T7SS) as a case study.
      Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and
      thus reduced secretion of T7SS-related effectors, probably due to the supporting
      scaffold activity of flotillin. We found that the presence of flotillin mediates
      intermolecular interactions of T7SS proteins. We tested several small molecules
      that interfere with flotillin scaffold activity, which perturbed T7SS activity in
      vitro and in vivo. Our results suggest that flotillin assists in the assembly of
      S. aureus membrane components that participate in infection and influences the
      infective potential of this pathogen.

PMID- 29166669
TI  - Frequency of five disease-causing genetic mutations in a large mixed-breed dog
      population (2011-2012).
AB  - BACKGROUND: A large and growing number of inherited genetic disease mutations are
      now known in the dog. Frequencies of these mutations are typically examined
      within the breed of discovery, possibly in related breeds, but nearly always in
      purebred dogs. No report to date has examined the frequencies of specific genetic
      disease mutations in a large population of mixed-breed dogs. Further,
      veterinarians and dog owners typically dismiss inherited/genetic diseases as
      possibilities for health problems in mixed-breed dogs, assuming hybrid vigor will
      guarantee that single-gene disease mutations are not a cause for concern.
      Therefore, the objective of this study was to screen a large mixed-breed canine
      population for the presence of mutant alleles associated with five autosomal
      recessive disorders: hyperuricosuria and hyperuricemia (HUU), cystinuria (CYST),
      factor VII deficiency (FVIID), myotonia congenita (MYC) and phosphofructokinase
      deficiency (PKFD). Genetic testing was performed in conjunction with breed
      determination via the commercially-available Wisdom PanelTM test. RESULTS: From a
      population of nearly 35,000 dogs, homozygous mutant dogs were identified for HUU
      (n = 57) and FVIID (n = 65). Homozygotes for HUU and FVIID were identified even
      among dogs with highly mixed breed ancestry. Carriers were identified for all
      disorders except MYC. HUU and FVIID were of high enough frequency to merit
      consideration in any mixed-breed dog, while CYST, MYC, and PKFD are vanishingly
      rare. CONCLUSIONS: The assumption that mixed-breed dogs do not suffer from single
      gene genetic disorders is shown here to be false. Within the diseases examined,
      HUU and FVIID should remain on any practitioner's rule-out list, when clinically
      appropriate, for all mixed-breed dogs, and judicious genetic testing should be
      performed for diagnosis or screening. Future testing of large mixed-breed dog
      populations that include additional known canine genetic mutations will refine
      our knowledge of which genetic diseases can strike mixed-breed dogs.

PMID- 29166670
TI  - Age-related differences in the respiratory microbiota of chickens.
AB  - In this era of next generation sequencing technologies it is now possible to
      characterise the chicken respiratory microbiota without the biases inherent to
      traditional culturing techniques. However, little research has been performed in
      this area. In this study we characterise and compare buccal, nasal and lung
      microbiota samples from chickens in three different age groups using 16S rRNA
      gene analysis. Buccal and nasal swabs were taken from birds aged 2 days (n = 5),
      3 weeks (n = 5) and 30 months (n = 6). Bronchoalveolar lavage (BAL) samples were
      also collected alongside reagent only controls. DNA was extracted from these
      samples and the V2-V3 region of the 16S rRNA gene was amplified and sequenced.
      Quality control and OTU clustering were performed in mothur. Bacterial DNA was
      quantified using qPCR, amplifying the V3 region of the 16S rRNA gene. We found
      significant differences between the quantity and types of bacteria sampled at the
      three different respiratory sites. We also found significant differences in the
      composition, richness and diversity of the bacterial communities in buccal, nasal
      and BAL fluid samples between age groups. We identified several bacteria which
      had previously been isolated from the chicken respiratory tract in culture based
      studies, including lactobacilli and staphylococci. However, we also identified
      bacteria which have not previously been cultured from the respiratory tract of
      the healthy chicken. We conclude that our study can be used as a baseline that
      future chicken respiratory microbiota studies can build upon.

PMID- 29166671
TI  - The 15N-leucine single-injection method allows for determining endogenous losses
      and true digestibility of amino acids in cecectomized roosters.
AB  - This study was conducted to assess the influence of dietary protein content in
      poultry when using the 15N-leucine single-injection method to determine
      endogenous amino acid losses (EAALs) in poultry. Forty-eight cecectomized
      roosters (2.39 +/- 0.23 kg) were randomly allocated to eight dietary treatments
      containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was
      precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all
      roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20
      mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta
      samples were continuously collected during the course of the 48-h experiment. The
      ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma
      ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05) across
      all treatments. The amino acid (AA) profiles of total endogenous AAs, except
      isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not
      influenced (P > 0.05) by dietary protein contents. The predominant endogenous AAs
      in the excreta were glutamic acid, aspartic acid, threonine, serine and proline.
      The order of the relative proportions of these predominant AAs also remained
      relatively constant (P > 0.05). The endogenous losses of total AAs determined
      with the 15N-leucine single-injection method increased curvilinearly with the
      dietary protein contents. The true digestibility of most AAs and total AAs was
      independent of their respective dietary protein levels. Collectively, the 15N
      leucine single-injection method is appropriate for determining EAALs and the true
      digestibility of AAs in poultry fed varying levels of protein-containing
      ingredients.

PMID- 29166672
TI  - Increased risk of dementia following herpes zoster ophthalmicus.
AB  - This retrospective cohort study aimed to examine the relationship between herpes
      zoster ophthalmicus (HZO) and the subsequent risk of dementia using a population
      based database. We retrieved the study sample from the Taiwan Longitudinal Health
      Insurance Database 2005. The study group included 846 patients with HZO, and the
      comparison group included 2538 patients without HZO. Each patient was
      individually followed for a 5-year period to identify those patients who
      subsequently received a diagnosis of dementia. We performed a Cox proportional
      hazards regression to calculate the hazard ratios (HRs) along with 95% confidence
      intervals (CIs) for dementia during the follow-up period between patients with
      HZO and comparison patients. The respective incidence rates of dementia per 1000
      person-years were 10.15 (95% CI: 7.22~13.87) and 3.61 (95% CI: 2.61~4.89) for
      patients with HZO and comparison patients. The Cox proportional analysis showed
      that the crude HR of dementia during the 5-year follow-up period was 2.83 (95%
      CI: 1.83-4.37) for patients with HZO than comparison patients. After adjusting
      for patients' characteristics and comorbidities, HZO patients were still at a
      2.97-fold greater risk than comparison patients for developing dementia.
      Furthermore, we found that of sampled male patients, the crude HR of dementia for
      patients with HZO was as high as 3.35 (95% CI = 1.79-6.28) compared to comparison
      patients. This study demonstrated an association between HZO and dementia.
      Clinicians must be alert to suspect dementia in patients with cognitive
      impairment who had prior HZO.

PMID- 29166673
TI  - Factors related to acupuncture response in patients with chronic severe
      functional constipation: Secondary analysis of a randomized controlled trial.
AB  - BACKGROUND: Acupuncture has been demonstrated to be effective and safe for
      chronic severe functional constipation (CSFC). However, which patients with CSFC
      will have a better response to acupuncture remains unclear. OBJECTIVE: To explore
      factors related to acupuncture response in patients with CSFC. METHODS: We
      performed a secondary analysis of a previous multicenter randomized controlled
      trial consisting of a 2-week run-in period, 8-week treatment, and 12-week follow
      up without treatment in which patients with CSFC were randomly allocated to an
      electroacupuncture group or a sham electroacupuncture group. Responders were
      defined as participants with an increase of at least one complete spontaneous
      bowel movement (CSBM) in week 20 compared with the baseline period. The CSBM
      responder rate in both groups was described, and the baseline characteristics of
      participants potentially related to acupuncture response were mainly analyzed
      using logistic regression analysis with bootstrapping techniques. RESULTS: A
      total of 1021 participants were analyzed in this study, of whom 516 (50.5%) were
      classified as responders. The CSBM responder rate in week 20 was significantly
      greater in the electroacupuncture group than in the sham electroacupuncture group
      (62.9% vs. 37.9%, respectively; P<0.001). Both age and comorbidity were
      negatively associated with clinical response: with every one-year increase in
      age, the likelihood of clinical response was reduced by 1.2% (OR 0.988, 95%CI
      0.980 to 0.996; P = 0.005), and patients with comorbidities were approximately
      42% less likely to respond to treatment (OR 0.581, 95%CI 0.248 to 0.914; P =
      0.001). CONCLUSION: CSFC patients with increasing age and comorbidity may be less
      likely to respond to acupuncture. These findings contribute to guiding clinical
      practice in terms of pretreatment patient selection. Further research is needed
      to confirm the association.

PMID- 29166675
TI  - Perianal Dermatitis, Its Incidence, and Patterns of Topical Therapies in a Level
      IV Neonatal Intensive Care Unit.
AB  - OBJECTIVE:  To define the incidence of perianal dermatitis (PD) and determine the
      usage pattern and cost efficacy of diaper products among neonates admitted to a
      level IV neonatal intensive care unit (NICU) including those with a diagnosis of
      neonatal abstinence syndrome (NAS). METHODS:  A retrospective cohort study to
      evaluate neonates with PD based on number of orders for Aquaphor, Bagbalm,
      Desitin, Flanders, or Nystatin. Various demographic and clinical parameters were
      recorded. Usage patterns of these five products were analyzed, and their costs
      estimated. Subgroup analysis was performed among infants with NAS. RESULTS:  Of
      1,241 admissions, 56.2% had at least one diaper product ordered during their NICU
      stay, while 52.6% had multiple products ordered. Only 23.0% of all neonates had
      appropriate documentation of PD. The most common product ordered first was
      Aquaphor (64.3%), followed by Desitin (19.2%). Note that 86% term NAS infants had
      PD compared with 28% term non-NAS infants. The estimated product cost was $14,139
      over 2 years, averaging $20 per patient. CONCLUSION:  Over half of NICU neonates
      were exposed to one or more diaper products, usually without documented PD
      diagnosis. Term NAS infants had three times higher incidence of PD than term non
      NAS infants. The cost of diaper product use was significant, and possibly
      underestimated due to lack of documentation.

PMID- 29166674
TI  - Unpredictable chronic mild stress differentially impairs social and contextual
      discrimination learning in two inbred mouse strains.
AB  - Alterations in the social and cognitive domain are considered important
      indicators for increased disability in many stress-related disorders. Similar
      impairments have been observed in rodents chronically exposed to stress,
      mimicking potential endophenotypes of stress-related psychopathologies such as
      major depression disorder (MDD), anxiety, conduct disorder, and posttraumatic
      stress disorder (PTSD). Data from numerous studies suggest that deficient
      plasticity mechanisms in hippocampus (HC) and prefrontal cortex (PFC) might
      underlie these social and cognitive deficits. Specifically, stress-induced
      deficiencies in neural plasticity have been associated with a hypodopaminergic
      state and reduced neural plasticity persistence. Here we assessed the effects of
      unpredictable chronic mild stress (UCMS) on exploratory, social and cognitive
      behavior of females of two inbred mouse strains (C57BL/6J and DBA/2J) that differ
      in their dopaminergic profile. Exposure to chronic stress resulted in impaired
      circadian rhythmicity, sociability and social cognition in both inbred strains,
      but differentially affected activity patterns and contextual discrimination
      performance. These stress-induced behavioral impairments were accompanied by
      reduced expression levels of brain derived neurotrophic factor (BDNF) in the
      prefrontal cortex. The strain-specific cognitive impairment was coexistent with
      enhanced plasma corticosterone levels and reduced expression of genes related to
      dopamine signaling in hippocampus. These results underline the importance of
      assessing different strains with multiple test batteries to elucidate the neural
      and genetic basis of social and cognitive impairments related to chronic stress.

PMID- 29166676
TI  - Comparison of Melatonin Levels in the Colostrum between Vaginal Delivery and
      Cesarean Delivery.
AB  - OBJECTIVE:  This study aims to compare melatonin levels in colostrum between
      vaginal and cesarean delivery. STUDY DESIGN:  This cross-sectional study was
      conducted with 139 mothers who gave live births between February 2016 and
      December 2016. The mothers were divided into three groups according to the mode
      of delivery: 60 mothers (43.2%) in the vaginal delivery group, 47 mothers (33.8%)
      in the elective cesarean delivery, and 32 mothers (23.0%) in the emergency
      cesarean delivery group. Colostrum of the mothers was taken between 01:00 and
      03:00 a.m. within 48 to 72 hours following the delivery, and the melatonin levels
      were measured using the enzyme-linked immunosorbent assay (ELISA) and compared
      between the groups. RESULTS:  The melatonin levels in the colostrum were the
      highest in the vaginal delivery group, lower in the elective cesarean section
      group, and the lowest in the emergency cesarean group (265.7 +/- 74.3, 204.9 +/-
      55.6, and 167.1 +/- 48.1, respectively; p < 0.001). The melatonin levels in the
      colostrum did not differ according to the demographic characteristics of the
      mothers, gestational age, birth weight, newborn sex, the Appearance, Pulse,
      Grimace, Activity, and Respiration (APGAR) scores, and for the requirement for
      neonatal intensive care. CONCLUSION:  Our study results showed that melatonin
      levels in the colostrum of the mothers who delivered vaginally were higher than
      those who delivered by cesarean section. Considering the known benefits of
      melatonin for the newborns, we believe that vaginal delivery poses an advantage.

PMID- 29166677
TI  - Severe Trampoline Injuries: Incidence and Risk Factors in Children and
      Adolescents.
AB  - INTRODUCTION:  Severe trampoline injuries in children and adolescents are rare;
      however, minor injuries are common and their incidence is increasing. Severe
      injuries are most commonly head and neck injuries. They may result in long-term
      morbidity. This study aimed to illustrate these severe injuries and to find out
      their incidence and risk factors. MATERIALS AND METHODS:  This is a population
      based, prospective study in the Oulu region of Finland completed over 2 years
      (May 1, 2015 to April 31, 2017). All children (<16 years of age) with severe
      trampoline injuries were included. Cervical spine fractures, chest wall and skull
      fractures, lesions of internal organs, hip and knee dislocations, and permanent
      disorders of the peripheral veins or nerves were in prior defined as severe.
      Multiple jumpers, stunts, younger age, previous injuries, insufficient use of
      safety equipment, and lack of supervision were hypothesized as risk factors.
      RESULTS:  There were 11 injured patients (10 boys). The annual incidence was
      6.28/100,000 children <16 years of age. Mean age was 11.5 years. Severe injuries
      included five ligamentous cervical spine injuries and two sternal bone fractures.
      In addition, there were one lumbar spine ligament injury, two hip dislocations,
      and one severe axillary plexus nerve lesion. Eight out of 11 accidents were not
      seen by any adult and none of them happened under professional supervision. Most
      injuries (N = 8) happened by failed backflips. CONCLUSION:  Most severe injuries
      happened in unsuccessful flips. Children should have an adult supervisor and
      flips should not be attempted.

PMID- 29166678
TI  - Laparoscopic Inguinal Hernia Repair in Infants and Children: State-of-the-Art
      Technique.

PMID- 29166679
TI  - Work-Related Musculoskeletal Disorders among Plastic Surgeons: A Systematic
      Review.
AB  - BACKGROUND:  To date, no review has been conducted on the growing body of
      literature describing various work-related musculoskeletal disorders (MSDs),
      ergonomic hazards, and potential interventions relevant to plastic surgeons. This
      systematic review sought to (1) define the scope of coverage of this important
      issue in the peer-reviewed literature; (2) critically assess the evidence; and
      (3) provide recommendations for future directions. METHODS:  We conducted a
      literature search of MEDLINE, Embase, Web of Science, and PubMed from the
      inception of each database until 2016. All articles reporting on work-related
      MSDs or ergonomics among plastic surgeons were reviewed, summarized, and assessed
      for trends. RESULTS:  Sixteen articles met our inclusion criteria including five
      expert opinions, four cross-sectional studies and case reports/series, one
      review, and six experimental studies. Four articles presented evidence on disease
      burden. The most commonly described work-related MSD was cervical spine disease,
      for which one study reported a career prevalence of 24.7% (point prevalence in
      the general population: 0.1-0.4%); three studies reported 64 cases of surgeon
      work-related MSD resulting in surgical intervention, decreased productivity, or
      involuntary early retirement. Eight studies described interventions, most of
      which aimed to improve the ergonomics of microsurgery. CONCLUSION:  This review
      found low-level evidence of plastic surgeons' vulnerability to a work-related MSD
      at times severe enough to end careers. Further investigation is needed to clearly
      define this important problem in plastic surgery. Specifically, future directions
      should include more methodologically rigorous epidemiologic studies evaluating
      disease burden.

PMID- 29166680
TI  - Knee Position during Surgical Wound Closure in Total Knee Arthroplasty: A Review.
AB  - Study areas concerning maximizing knee range of motion (ROM) following total knee
      arthroplasty (TKA) have come under focus by surgeons. Among the perioperative
      factors that were identified to affect ROM after TKAs is knee position during
      surgical wound closure. Therefore, the aim of this study was to review the impact
      of knee position during TKA wound closure on: (1) postoperative ROM, (2) wound
      related complications, (3) Knee Society Score (KSS), (4) postoperative pain, and
      (5) muscle strength and home functional recovery. A literature search was
      performed using PubMed, Ovid, and Google Scholar using various combinations of
      the following search terms: "wound closure," "knee position," "surgical closure,"
      and "knee arthroplasty." The studies were evaluated for outcomes after TKA and
      stratified based on the knee position at surgical closure. After application of
      inclusion and exclusion criteria, seven studies were analyzed. The total number
      of patients included was 516 patients (259 patients in the flexion group and 257
      patients in the full extension group). Based on the reviewed literature, wound
      closure in flexion was associated with significant improvement in ROM recovery at
      earlier follow-ups after TKA (four positive and three neutral studies), better
      early postoperative pain scores (two positive and one neutral study), and faster
      physical recovery (two positive studies) (better muscle strength and early
      achievement of physical therapy milestones) compared with wound closure in
      extension. No difference was found between wound closure in flexion compared with
      closure in extension in terms of long-term ROM recovery, long-term postoperative
      pain scores, wound-related complications (seven neutral studies), knee function
      measured by KSS (five neutral studies), or patient satisfactions after TKA.
      Although the current review is limited by the number of studies that are
      available in the literature, it demonstrates that overall, compared with
      extension, surgical wound closure in flexion may provide better ROM, faster
      recovery, comparable patient satisfaction, and no risk of higher wound
      complications.

PMID- 29166681
TI  - Difficult Cases in Robotic Arm-Assisted Total Knee Arthroplasty: A Case Series.
AB  - Sagittal deformity of the knee is commonly corrected to neutral biomechanical
      axis (+/-3 degrees) during total knee arthroplasty (TKA), which is a widely
      accepted goal. Recent advances in surgical technology have made it possible to
      accurately plan and fulfill these goals. One of these is robotic-assisted TKA,
      which has been noted to help increase accuracy and precision of restoring a
      neutral mechanical axis. While there are data confirming the ability of robotic
      devices to better correct knee alignment than the manual technique, there is a
      lack of data concerning the use of the robotic devices in more complex cases,
      such as those in patients with severe varus or valgus deformity, as well as in
      flexion contractures. Therefore, the purpose of this case study is to present
      three cases in which the robotic-assisted TKA device was used to correct a severe
      varus and severe valgus deformities. Based on this case series, it should be
      noted that the robotic device can also help correct severe varus/valgus
      deformities and flexion contractures.

PMID- 29166682
TI  - Bone Marrow Cellular Therapies: Novel Therapy for Knee Osteoarthritis.
AB  - Cellular therapies are emerging as potentially promising treatments for numerous
      musculoskeletal conditions, such as knee osteoarthritis (OA). As orthopaedic
      surgeons represent a sizable portion of the providers who deliver these
      therapies, it is particularly essential for them to understand their fundamental
      principles. One major principle is to identify the appropriate sources for
      obtaining these cells, with bone marrow being most common. Therefore, the purpose
      of this review was to provide an overview of cell-based therapies available for
      the treatment of knee OA with a focus on bone marrow-derived cellular therapies.
      Specifically, we discuss (1) bone marrow aspiration technique, (2) processing to
      bone marrow aspirate concentrate, and (3) the rational and clinical evidence for
      the use of bone marrow cellular therapies for the treatment of knee OA.

PMID- 29166683
TI  - The Learning Curve Associated with Robotic Total Knee Arthroplasty.
AB  - As with most new surgical technologies, there is an associated learning curve
      with robotic-assisted total knee arthroplasty (TKA) before surgeons can expect
      ease of use to be similar to that of manual cases. Therefore, the purpose of this
      study was to (1) assess robotic-assisted versus manual operative times of two
      joint reconstructive surgeons separately as well as (2) find an overall learning
      curve. A total of 240 robotic-assisted TKAs performed by two board-certified
      surgeons were analyzed. The cases were sequentially grouped into 20 cases and a
      learning curve was created based on mean operative times. For each surgeon, mean
      operative times for their first 20 and last 20 robotic-assisted cases were
      compared with 20 randomly selected manual cases performed by that surgeon as
      controls prior to the initiation of the robotic-assisted cases. Each of the
      surgeons first 20 robotic assisted, last 20 robotic assisted, and 20 controls
      were then combined to create 3 cohorts of 40 cases for analysis. Surgeon 1: First
      and last robotic cohort operative times were 81 and 70 minutes (p < 0.05). Mean
      operative times for the first 20 robotic-assisted cases and manual cases were 81
      versus 68 minutes (p < 0.05). Mean operative times for the last 20 robotic
      assisted cases and manual cases were 70 versus 68 minutes (p > 0.05). Surgeon 2:
      First and last robotic cohort operative times were 117 and 98 minutes (p < 0.05).
      Mean operative times for the first 20 robotic-assisted cases and manual cases
      were 117 versus 95 (p < 0.05). Mean operative times for the last 20 robotic
      cohort cases and manual cases were 98 versus 95 (p > 0.05). A similar trend
      occurred when the times of two surgeons were combined. The data from this study
      effectively create a learning curve for the use of robotic-assisted TKA. As both
      surgeons completed their total cases numbers within similar time frames, these
      data imply that within a few months, a board-certified orthopaedic joint
      arthroplasty surgeon should be able to adequately perform robotic TKA without
      adding any operative times.

PMID- 29166684
TI  - [Implantation of a Modular Distal Femoral Replacement with Compressive
      Osseointegration as a Salvage Procedure in a Complex Femoral Posttraumatic
      Setting].
AB  - BACKGROUND: Large bone defects and losses play a crucial role in both tumour
      surgery and in complex primary and revision total knee replacement. The
      established options of cemented or uncemented long intramedullary stems are
      limited by large bone defects and are at risk from relatively high exposure to
      aseptic loosening. There is no general valid agreement on implant fixation of the
      distal femur. A further option is the cementless fixation method with compressive
      osseointegration, based on the so-called Wolff law of bone remodelling. This
      method was developed in order to reduce the high loosening rates in revision
      arthroplasty due to intense stress shielding and is intended to be applied in
      patients with huge bone losses. The so-called Compress(r) system (or CPS) allows
      such a distal femur reconstruction. It has mainly been applied and evaluated in
      tumor endoprosthetics. There are currently few data on the application of this
      system in complex distal femoral posttraumatic deformity or revision
      arthroplasty. PATIENTS: A case report of two male patients aged 59/56 years with
      a 1-year follow-up is presented. Both patients had a complex post-traumatic
      femoral deformity with bone loss, prior surgery and an ipsilateral hip
      replacement. Implantation was performed of a modular total knee replacement,
      consisting of a cemented modular tibia base plate and distal femoral replacement
      with cementless implant fixation by compressive osseointegration. Both patients
      were clinically and radiologically evaluated prospectively. RESULTS: Good
      clinical and radiological results were demonstrated in both patients after distal
      femoral replacement by compressive osseointegration. There was no need for
      further or revision surgery. Both patients were rapidly able to resume their
      jobs. The survival rates for CPS were comparable to published values with
      conventional procedures. There are yet no long-term results or extensive data for
      revision arthroplasty or posttraumatic cases. CONCLUSIONS: Besides distal femoral
      replacement with compressive osseointegration in oncological arthroplasty, the
      indication of complex distal femoral settings with large bone defects can be
      evaluated for daily clinical routine. Especially if there is ipsilateral total
      hip replacement, this option might be used to avoid interprosthetic stress
      risers.

PMID- 29166685
TI  - [Evaluation of Inpatient Conservative Management of Acute, Subacute, and Chronic
      Back Pain].
AB  - BACKGROUND: Backache is very common in the German population. It is a common
      reason for people to seek medical advice and specific back pain programs have
      been developed. The intention of this study is to evaluate the short and long
      term effects of conservative management of back pain in a German general
      hospital. Outcomes of interest were pain intensity, interference in daily
      functions, physical functioning and health related quality of life. PATIENTS AND
      METHODS: We examined 1010 patients with acute, subacute and chronic back pain,
      admitted to inpatient nonsurgical interventional therapy in a German hospital
      between July 2013 and July 2015. Outcomes were assessed at the end of the
      inpatient treatment and at 3, 6 and 12 months follow-up, using Numerical Rating
      Scales (NRS) for pain and daily function, the Hannover Ability Questionnaire for
      Measuring Back Pain-Related Functional Limitations (FFbH - R) and the German
      Version of the EuroQol Questionnaire (EQ-5D) for measuring health-related quality
      of life. The baseline questionnaire also included questions on the risk of
      developing long-term disability following back pain (HKF-R 10) for acute and
      subacute cases and the Mainz Pain Staging System (MPSS) for patients with chronic
      back pain. The return rate was 54% after 3 months, 38% after 6 months and 27% at
      12 months follow-up. The results from the follow-up measurements (T2 - T5) were
      compared to the pre-treatment results (T1). Because of missing or insufficiently
      normal distributions nonparametric paired Wilcoxon tests were used to test
      differences over time for each variable. Level of significance was adjusted for
      multiple testing. In addition, effect sizes were computed to estimate the
      clinical relevance of statistically significant results. RESULTS: Pain intensity
      and impact of pain on daily function were significantly lower at the end of the
      inpatient treatment (T2). The results remained largely stable at the 3, 6 and 12
      month follow-ups. Significant improvements were found in physical functioning and
      health-related quality of life. These improvements were maintained equally at the
      3, 6 and 12 month follow-ups. In consequence, working ability increased during
      the follow-up period. Calculated effect sizes showed large effects for pain
      intensity, interference and quality of life (r = 0.51 to 0.85) and predominately
      moderate effects (r = 0.45 to 0.62) for physical functioning at all measurement
      points. The percentage of patients who had an operation due to continuing back
      pain after conservative treatment was 7.8, 9.9, and 12.3 at the 3, 6, and 12
      month follow-ups, respectively. CONCLUSION: Persistent effects of inpatient
      conservative treatment of back pain were found for all outcome variables. The
      specific approach appears to be effective in conservative treatment programs of
      back pain. In the end, it's not about the alternative of surgery or conservative
      treatment for back pain. Treatment has to be coordinated with the patient in
      terms of participative decisions.

PMID- 29166686
TI  - [Bone Cement Adhesion on Ceramic Surfaces - Deactivation of Surfaces and as a
      Consequence Inefficient Retention of Knee Prostheses Because of Adsorption of
      Atmospheric Water].
AB  - AIM: CoCrMo alloys are contraindicated for sufferers from allergy. For these
      patients, uncemented and cemented prostheses made of non-allergenic titanium
      alloy are indicated. Knee prostheses machined from that alloy, however, may have
      poor tribological behaviour, especially in contact to UHMWPE inlays. Therefore,
      high-strength oxide ceramics may be especially suitable for knee replacement in
      allergy patients with mobile bearing prostheses. For adhesion to bone cement, the
      ceramic surface only exhibits mechanical retention spots that are less adequate
      than those with a textured metal surface. Generating undercuts by corundum
      blasting is highly efficient for mechanical adhesion to a CoCrMo surface, but is
      not possible on a ceramic surface, due to the brittleness of ceramics. Lack of
      retention of bone cement promotes micromotions of the prostheses. As a
      consequence of micromotions, early aseptic loosening is predictable. Silicoating
      (silicate and silane layering) of the ceramic surface would allow specific
      adhesion and hence would result in increased and hydrolytically more stable
      bonding between the bone cement and the prosthesis surface - thereby preventing
      early aseptic loosening. Silicoating, however, presupposes a chemically active
      surface that is not blocked by a layer of chemisorbed molecules, e.g. water.
      Desorption of this chemisorbed layer is mandatory and can be attained by baking
      out the surface. METHOD: In order to evaluate the effectiveness of surface
      activation via thermal treatment by baking out, with subsequent silicoating of
      the surface, the bond strengths of thermally treated and silicate layered ZPTA
      samples were compared with thermally treated surfaces that had not been
      silicoated. In our study of thermal surface treatment for baking out the surface,
      we focused on the question of whether there is a minimal "critical" temperature
      Ts for effective desorption of a chemisorbed water layer. The samples were
      prepared for the traction-adhesive strength test (sequence: ceramic disc,
      silicate and silane layering, protective lacquer ("PolyMA" layer), bone cement,
      TiAlV probes for the traction-adhesive strength test) and their traction-adhesive
      strengths were then measured. RESULTS: The bond strength was measured as a
      function of temperature for ceramic discs that had been baked out and
      subsequently silicoated. This was graduated, exhibits with a pronounced increase
      in the bond strength at a baking temperature of Ts ~ 350  degrees C. The observed
      bond strengths before the step are <= 20 MPa and after the step >= 30 MPa.
      CONCLUSION: Silicoating is effective in achieving high bond strength of bone
      cement on surfaces of oxide ceramics and can also stabilise the long term
      behaviour of the bond strength, provided the surface has been thermally treated
      prior to silicoating. Because of the proposed migration of the silicoating layer,
      micromotions and debonding should be widely reduced or even eliminated.

PMID- 29166687
TI  - [How Probable is it That Seniors Using an E-Bike Will Have an Accident? - A New
      Health Care Topic, Also for Consulting Doctors].
AB  - BACKGROUND: In Germany there are more than 70 million bicycles. Because of
      technical progress, over 200,000 electro-assisted bikes were sold in Germany in
      2010 alone. In 2013, the number increased to 410,000. Currently more than 1.6
      million electric bicycles are used here. One of the largest user groups are
      seniors. Accident researchers fear an increased risk of accidents/injuries.
      METHODS: For one year, all cycling accidents involving electric bicycles and
      senior citizens were collected and analysed in 23 hospitals of the TraumaNetwork
      NorthWest and by the local police authorities. RESULTS: A comparison of the
      senior and younger electro-assisted cyclists showed a higher risk of injury for
      seniors in the initial analysis. A further comparative analysis of severely
      injured seniors who were riding an electro-assisted bike with those who used a
      conventional bicycle contradicted this. There was no statistical significance.
      The risk of an accident increased with age, but not with bicycle type.
      CONCLUSION: To reduce accidents, driving training and medical precautionary
      examinations could be used to detect losses of performance, cognitive processing
      and balance. In the future, they should become an integral part of the health
      care system and the services of practicing physicians.

PMID- 29166688
TI  - [Perioperative Management in Total Knee Arthroplasty].
AB  - The themes of this paper are the clinical relevance and technique of
      perioperative management in total knee arthroplasty. Due to the number of
      unsatisfied patients after knee arthroplasty, optimisation of processes seems to
      be necessary. Beside patient preparation and rehabilitation, the surgical
      technique and implant choice in perioperative management are important. This
      means the use of tourniquet and drains, the application of tranexamic acid and
      pain management. These items are presented and discussed in detail in this paper.

PMID- 29166689
TI  - [New Challenges for Psychiatry].

PMID- 29166690
TI  - [Facial emotion recognition, theory of mind and empathy in multiple sclerosis].
AB  - Multiple sclerosis (MS), a chronic progressive inflammatory disease of the
      central nervous system, causes frequent disability, mood disorders, fatigue, and
      cognitive dysfunction. As a part of the last, social cognition is frequently
      disturbed in MS patients. It comprises empathy and social perception of emotions
      from facial, bodily and vocal cues. Social cognitive deficits worsen affect
      decoding, interpersonal relationship, and quality of life. Despite the impact of
      these deficits on global functioning, only a small number of studies have
      investigated its correlations and overlaps with MS symptoms. This review focuses
      on the definition and anatomy of social cognition and draws attention to findings
      of neuropsychological and neuroimaging studies on social cognitive performance in
      MS.Results of the available studies show that social cognitive deficits are
      already measurable in early stages of MS. Over time course of the disease,
      neuropsychological and neuroimaging studies show an increase of disease burden
      and social and non-social cognitive impairment following the hypothesis of a
      disconnection syndrome resulting from gray and white matters lesions. These
      structural changes might exceed a threshold of compensatory restorative and
      neuroplasticity mechanisms and finally lead to deficits in social cognition.
      Considering this burden in social functioning, a further assessment of
      sociocognitive deficits in MS is urgently needed to provide specific therapeutic
      approaches and to improve quality of life.

PMID- 29166691
TI  - [Emil Kraepelin's time in Dorpat - Did this stay made marks in Russian and Soviet
      psychiatry?]
AB  - In Russia, German psychiatrist Emil Kraepelin (1856-1926) is regarded as an
      influential and famous personality in the history of the field. This study
      discusses whether it was his period in the Russian Empire in the years 1886 to
      1891 when he worked at Dorpat University (today Tartu, Estonia) that raised his
      popularity in Russia. Our research shows that all of his writings which had been
      translated into Russian language derive from a period much later than Dorpat.
      Moreover, none of his students has ever reached a scientific position which would
      have enabled him to become a proponent of Kraepelin's ideas in Russia. Despite
      his stay at Dorpat was important for Kraepelin's scientific development, it had
      no major impact on Russian psychiatry.The later perception of Kraepelin in Russia
      and in the Soviet Union is quite inconsistent. At some point of time, his works
      on experimental psychology were appreciated, which was probably connected with
      the rise of reflexology in Russian and, especially, Soviet psychiatry. On the
      other hand, it was Kraepelin's merits in the classification of psychiatric
      diseases that have mainly been acknowledged.

PMID- 29166693
TI  - [The biased expert: An unknown quantity].
AB  - Academic publications have so far hardly paid any attention to the topic of
      biased medical experts or expert opinions. This is the first attempt to
      systematically describe and analyze the issue, drawing on the author's many years
      of giving expert opinions as a neuropsychiatrist on matters relating to social
      legislation and civil law. In addition to dealing with questions of definition,
      this article outlines the features of biased expert opinions, particularly
      focusing on the role of insurance and private experts. Finally, proposals are
      made to initiate a discussion on how to prevent biased expert opinions and
      improve their registration.

PMID- 29166692
TI  - [Neurological or interdisciplinary outpatient pain treatment: comparison of
      treatment success and satisfaction].
AB  - The aim of this study was to compare the satisfaction and success of treatment
      for pain patients who were interdisciplinary (anaesthesiological, psychosomatic,
      neurological, orthopedic) treated or underwent neurological care alone. Methods
      We selected 183 patients who were treated in our neurological clinic and in our
      interdisciplinary pain management center (IST). Of these, 142 patients having
      polyneuropathy, headache or muskuloskelettal pain were included in the final
      analysis. 39 patients (27.5 %) were treated in the IST and 103 patients were
      treated exclusively by a neurologist. These patients were asked to complete a
      questionnaire, and were queried about the satisfaction and pain parameters.
      Results The neurological and multidisciplinary pain treatment led to a similar
      improvement in pain (p < 0.001). This effect was independent of the underlying
      disease. The interdisciplinary outpatient treatment resulted not primarily in an
      increased patient satisfaction. Conclusions The reduction of pain and patient
      satisfaction of neurological outpatient pain treatment were comparable with those
      of a multidisciplinary outpatient therapy. The only significant advantage of the
      interdisciplinary treatment was lower hospitalization rate after therapy. This
      result cannot evaluate the efficiency of inpatient or day hospital pain
      management, but suggests that in many cases a neurological outpatient pain
      therapy is sufficient, so that neurological outpatient care should be promoted.

PMID- 29166694
TI  - ?

PMID- 29166695
TI  - [Without Net and Double Floor: Comparison of Umbilical Hernia Repair by Spitzy in
      Children and Adults].
AB  - Summary Umbilical hernia occur in both adults and children. For over 100 years,
      umbilical hernia in children has been treated surgically by the Spitzy method.
      With adult patients, meshes are being increasingly used. The purpose of our study
      was to analyse Spitzy herniotomy with respect to the recurrence rate in children
      and adults. Material and Methods Over a period of 7 years, 383 children (age < 16
      years) with umbilical hernia were treated surgically; after applying the
      exclusion criteria, 370 patients were evaluated. At the same time, 106 adult
      patients (age > 16 years) were operated for an umbilical hernia: 31 patients were
      treated with direct suture and thus are included in our study as comparison
      group. Results The young patients had an average age of 33.81 months and were 44%
      female and 56% male. After direct Spitzy suture, a low recurrence rate of 1.1% (n
      = 4) in infancy could be achieved. The average age of the adult patients was
      54.55 years; 32% were female, 68% male. In comparison to the group of children,
      the recurrence rate in adult surgery was 12.9% (n = 4) after direct suture.
      Conclusion As confirmed in our study, umbilical herniotomy by direct suture in
      childhood has been the method of choice and gold standard for more than 100
      years. Mesh implantation is still not necessary in childhood.

PMID- 29166696
TI  - [Fluorescence Cholangiography in Comparison to Radiographic Cholangiography
      During Laparoscopic Cholecystectomy].
AB  - BACKGROUND: The reported incidence rate of bile duct injury (BDI) during
      laparoscopic cholecystectomy (LC) is 0.3%. However, routine use of intraoperative
      cholangiography (IOC) is a controversial, due to the additional cost and
      radiation exposure. The aim of this study was to assess the application of
      fluorescence cholangiography (FC) in comparison to IOC and to LC without any
      intraoperative imaging. MATERIALS AND METHODS: This prospective study included
      230 patients undergoing LC in our institution. The subjects were divided into two
      groups. In the first group, with 170 patients, both FC and IOC were performed
      following a standardised protocol. In second group, with 60 patients, FC was
      compared to LC without any intraoperative imaging. The data were then analysed
      with respect to procedure time and identification of predefined anatomical
      structures. RESULTS: The mean age and body mass index in the first group were
      54.4 +/- 15.7 years and 27.9 +/- 5.7 kg/m2, respectively. The mean operative time
      was 67.6 +/- 23.3 min. FC was performed more rapidly than IOC (1.5 +/- 0.9 vs.7.3
      +/- 5.0 min) and visualised the cystic duct (DC) in 67.5% of patients and the
      common bile duct (DHC) in 66.2% of patients before dissection of Calot's
      triangle. During dissection, DC and DHC were detected in 95.9% and 71.2% of
      patients, respectively. BMI > 25 kg/m2 and male gender significantly reduced the
      identification rate of DC before dissection of Calot's triangle. Bile leakage
      from the liver bed after cholecystectomy was found in 3 cases (1.8%) by FC. In 2
      patients (1.2%), IOC visualised the DC joining directly to the right hepatic
      duct. In 1 of these 2 cases (0.6%), the anatomical variation was identified first
      by FC. Intraductal filling defects were detected in 9 patients (5.3%) using IOC,
      compared to 1 patient (0.6%) using FC. In the second group, the visualisation
      rates of DC and DHC were 80.0 and 53.3%, respectively, with FC and 60.0 and
      43.3%, respectively, during LC without any imaging. Surgeons confirmed an
      increase in safety in 70.0% of patients using FC. CONCLUSION: FC is a simple
      procedure for non-invasive real-time visualisation of bile duct anatomy during
      LC. Earlier identification of biliary anomalies and bile leakage increases the
      operative safety and enables immediate care. In obese patients, FC has limited
      validity.

PMID- 29166697
TI  - [Patient-unrelated Risk Factors for the Development and Treatment Course of
      Anastomotic Failure in Colorectal Surgery - Results of Structured M+M
      Conferences].
AB  - BACKGROUND: There are numerous published studies on patient-related risk factors
      for the development of anastomotic failure. We therefore investigated the
      influence of patient-unrelated risk factors for the development and course of
      treatment of anastomotic failure in colorectal surgery. PATIENT SAMPLE: From May
      1, 2015, until December, 31, 2016, n = 179 post-colorectal surgery patients were
      analysed. Overall, n = 14 patients suffered from anastomotic failure. These
      patients' course of treatment was analysed in a Morbidity and Mortality
      Conference (M+M conference) structured according to the London Protocol. RESULTS:
      Irregularities in process quality were the most frequent analysis result (n =
      8/14), followed by irregularities in post-treatment (n = 6/14). Irregularities in
      surgical technique (n = 2/14) and surgery procedure (n = 3/14) were less
      frequent. Future treatment approaches were identified for most patients (n =
      11/14). On the basis of the analysis of data from four of these eleven patients,
      the strategy for future treatment was modified. CONCLUSION: Therapist- and
      environment-specific irregularities can be systematically identified in M+M
      conferences structured according to the London Protocol. This analysis is the
      prerequisite for quality improvement and must systematically complement the
      analysis of patient-related risk factors.

PMID- 29166698
TI  - [The Value of Endoscopic Decompression in Surgical Therapy of Carpal Tunnel
      Syndrome].
AB  - Carpal tunnel syndrome is one of the most common diseases in hand surgery. The
      gold standard in therapy is the surgical release of the carpal tunnel. We provide
      a brief update on the relevant pathogenesis, diagnosis and therapy and discuss
      questions related to minimal invasive decompression of the median nerve. Together
      with a review of the current literature, we report on our experiences in
      minimally invasive carpal tunnel release via a monoportal endoscopic access in
      over 700 cases. In conclusion, the endoscopic technique provides superior
      convalescence and patient safety is comparable to open methods. In addition,
      advantages and disadvantages of the various techniques are discussed.

PMID- 29166699
TI  - Comparison of clinical outcomes of coronary artery stent implantation in patients
      with end-stage chronic kidney disease including hemodialysis for three everolimus
      eluting (EES) stent designs: Bioresorbable polymer-EES, platinum chromium-EES,
      and cobalt chrome-EES.
AB  - BACKGROUNDS: New-generation bioresorbable polymer-everolimus eluting stents (BP
      EES) are available. This study aimed to compare the clinical outcomes for BP-EES
      compared to more established stent designs, namely the platinum chromium-EES
      (PtCr-EES) and cobalt chrome-EES(CoCr-EES) in patients with the end-stage chronic
      kidney disease (CKD) including hemodialysis (HD). METHODS: One-hundred-forty-one
      consecutive stents (BP-EES [n = 44], PtCr-EES [n = 45], and CoCr-EES [n = 52])
      were implanted in 104 patients with CKD. All patients underwent a follow-up
      coronary angiography at 12 months after implantation. End-stage CKD was defined
      as an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 , or the
      need for HD. The following outcome variables were compared among the three stent
      groups after implantation and the 12-month follow-up: target lesion
      revascularization (TLR), stent thrombosis (ST), and major adverse cardiac event
      (MACE). Minimal stent diameter (MSD) and %diameter-stenosis (%DS) were measured
      using quantitative coronary angiography. RESULTS: The overall rate of TLR and
      MACE was 14.6% and 30.8%, respectively, with no incidence of ST. Immediately
      after implantation, the MSD (P = 0.22) and %DS (P = 0.42) were equivalent among
      the three groups. However, at the 12-month follow-up, a tendency towards higher
      TLR was observed for the BP-EES group (22.7%) compared with the PtCr-EES (8.8%)
      and CoCr-EES (9.6%) groups (P = 0.07). Late loss in lumen diameter was also
      significantly greater for the BP-EES (0.51 +/- 0.64 mm) group than either the
      PtCr-EES (0.20 +/- 0.61 mm) and CoCr-EES (0.25 +/- 0.70 mm) groups (P = 0.03).
      CONCLUSIONS: BP-EES might increase the risk of in-stent restenosis in patients
      with end-stage of CKD or the need for HD.

PMID- 29166700
TI  - DLP1-dependent mitochondrial fragmentation and redistribution mediate prion
      associated mitochondrial dysfunction and neuronal death.
AB  - Mitochondrial malfunction is a universal and critical step in the pathogenesis of
      many neurodegenerative diseases including prion diseases. Dynamin-like protein 1
      (DLP1) is one of the key regulators of mitochondrial fission. In this study, we
      investigated the role of DLP1 in mitochondrial fragmentation and dysfunction in
      neurons using in vitro and in vivo prion disease models. Mitochondria became
      fragmented and redistributed from axons to soma, correlated with increased
      mitochondrial DLP1 expression in murine primary neurons (N2a cells) treated with
      the prion peptide PrP106-126 in vitro as well as in prion strain-infected hamster
      brain in vivo. Suppression of DLP1 expression by DPL1 RNAi inhibited prion
      induced mitochondrial fragmentation and dysfunction (measured by ADP/ATP ratio,
      mitochondrial membrane potential, and mitochondrial integrity). We also
      demonstrated that DLP1 RNAi is neuroprotective against prion peptide in N2a cells
      as shown by improved cell viability and decreased apoptosis markers, caspase 3
      induced by PrP106-126 . On the contrary, overexpression of DLP1 exacerbated
      mitochondrial dysfunction and cell death. Moreover, inhibition of DLP1 expression
      ameliorated PrP106-126 -induced neurite loss and synaptic abnormalities (i.e.,
      loss of dendritic spine and PSD-95, a postsynaptic scaffolding protein as a
      marker of synaptic plasticity) in primary neurons, suggesting that altered DLP1
      expression and mitochondrial fragmentation are upstream events that mediate
      PrP106-126 -induced neuron loss and degeneration. Our findings suggest that DLP1
      dependent mitochondrial fragmentation and redistribution plays a pivotal role in
      PrPSc -associated mitochondria dysfunction and neuron apoptosis. Inhibition of
      DLP1 may be a novel and effective strategy in the prevention and treatment of
      prion diseases.

PMID- 29166701
TI  - When is protection from impact needed for the face as well as the eyes in
      occupational environments?
AB  - BACKGROUND: The most commonly identified reason for requiring or using
      occupational eye and face protection is for protection against flying objects.
      Standards vary on what risk may require protection of the eyes alone and what
      requires protection for the whole face. Information on the minimum energy
      transfer for face damage to occur is not well-established. METHODS: The heads of
      pigs were used as the common model for human skin. A 6 mm steel ball projected at
      velocities between 45 and 135 m/s was directed at the face area. Examples of
      impacts were filmed with a high-speed camera and the resulting damage was rated
      visually on a scale from 1 (no visible damage) to 5 (penetrated the skin and
      embedded in the flesh). RESULTS: The results for the cheek area indicate that 85
      m/s is the velocity above which damage is more likely to occur unless the skin
      near the lip is included. For damage to the lip area to be avoided, the velocity
      needs to be 60 m/s or less. CONCLUSION: The present data support a maximum impact
      velocity of 85 m/s, provided the thinner and more vulnerable skin of the lids and
      orbital adnexa is protected. If the coverage area does not extend to the orbital
      adnexa, then the absolute upper limit for the velocity is 60 m/s. At this stage,
      eye-only protection, as represented by the lowest level of impact test in the
      standards in the form of a drop ball test, is not in question.

PMID- 29166702
TI  - Impact of active cancer disease on the outcome of patients undergoing
      transcatheter aortic valve replacement.
AB  - BACKGROUND: Patients undergoing transcatheter aortic valve replacement (TAVR) are
      often characterized by risk factors not reflected in conventional risk scores. In
      this context, little is known about the outcome of patients suffering from an
      active cancer disease (ACD). The objective was to determine the prevalence,
      clinical characteristics, perioperative outcomes, and mortality of patients with
      ACD undergoing TAVR compared to those with a history of cancer (HCD) and controls
      without known tumor disease. METHODS: TAVR patients between 02/2006 and 09/2014
      were stratified according to the presence of ACD, HCD, and control. All-cause
      mortality at 1-year was the primary end point. All end point definitions were
      subject to the Valve Academic Research Consortium II definitions. RESULTS:
      Overall, 1821 patients were included: 99 patients (5.4%) suffered from ACD and
      251 patients (13.8%) had HCD. ACD was related to a solid organ or hematological
      source in 72.7% and 27.3%, respectively. Patients with ACD were more often male
      (P = 0.004) and had a lower logisticEuroScore I (P = 0.033). Overall rates of
      VARC-II defined periprocedural myocardial infarction, stroke, bleeding, access
      site complications, and acute kidney injury were not different between groups.
      Thirty-day mortality did not differ between patients with ACD, HCD, and controls
      (6.1% vs 4.4% vs 7.6%, P = 0.176). All-cause 1-year mortality was higher in
      patients with ACD compared HCD and controls (37.4% vs 16.4% vs 20.8%, P < 0.001).
      ACD was an independent predictor of all-cause 1-year mortality (HR 2.10, 95%-CI
      1.41-3.13, P < 0.001). CONCLUSION: The presence of ACD in patients undergoing
      TAVR is associated with significantly higher 1-year mortality.

PMID- 29166703
TI  - In-hospital outcomes in invasively managed acute myocardial infarction patients
      who receive morphine.
AB  - OBJECTIVE: We aimed to analyze the association between morphine and in-hospital
      outcomes in invasively managed ST elevation myocardial infarction (STEMI) and non
      ST elevation acute coronary syndrome (NSTE-ACS) patients. BACKGROUND: Morphine is
      commonly used for analgesia in the setting of acute coronary syndromes (ACS);
      however, recently its utility in ACS has come under closer scrutiny. METHODS: We
      identified all STEMI and NSTE-ACS patients undergoing coronary angiogram +/-
      percutaneous intervention between January 2009 and July 2016 in our center and
      recorded patient characteristics and inpatient outcomes. RESULTS: Overall, 3027
      patients were examined. Overall, STEMI patients who received morphine had no
      difference in in-hospital mortality [4.18% vs. 7.54%, odds ratio (OR): 0.36, P =
      0.19], infarct size (mean troponin level 0.75 ng/mL vs. 1.29 ng/mL, P = 0.32) or
      length of hospital stay (P = 0.61). The NSTE-ACS patients who received morphine
      had a longer hospital stay (mean 6.58 days vs. 4.78 days, P < 0.0001) and larger
      infarct size (mean troponin 1.16 ng/mL vs. 0.90 ng/mL, P = 0.02). Comparing
      matched patients, the use of morphine was associated with larger infarct size
      (mean troponin 1.14 +/- 1.92 ng/mL vs. 0.83 +/- 1.49 ng/mL, P = 0.01), longer
      hospital stay (6.5 +/- 6.82 days vs. 4.89 +/- 5.36 days, P = 0.004) and a trend
      towards increased mortality (5% vs. 2%, OR: 2.55, P = 0.06) in NSTE-ACS patients
      but morphine did not affect outcomes in the propensity matched STEMI patients.
      CONCLUSION: In a large retrospective study, morphine was associated with larger
      infarct size, a longer hospital stay and a trend towards increased mortality in
      invasively managed NSTE-ACS patients even after adjustment for clinical
      characteristics.

PMID- 29166704
TI  - The prevalence and causes of visual impairment in seven-year-old children.
AB  - BACKGROUND: To report the prevalence and causes of visual impairment in seven
      year-old children in Iran and its relationship with socio-economic conditions.
      METHODS: In a cross-sectional population-based study, first-grade students in the
      primary schools of eight cities in the country were randomly selected from
      different geographic locations using multistage cluster sampling. The
      examinations included visual acuity measurement, ocular motility evaluation, and
      cycloplegic and non-cycloplegic refraction. Using the definitions of the World
      Health Organization (presenting visual acuity less than or equal to 6/18 in the
      better eye) to estimate the prevalence of vision impairment, the present study
      reported presenting visual impairment in seven-year-old children. RESULTS: Of
      4,614 selected students, 4,106 students participated in the study (response rate
      89 per cent), of whom 2,127 (51.8 per cent) were male. The prevalence of visual
      impairment according to a visual acuity of 6/18 was 0.341 per cent (95 per cent
      confidence interval 0.187-0.571); 1.34 per cent (95 per cent confidence interval
      1.011-1.74) of children had visual impairment according to a visual acuity of
      6/18 in at least one eye. Sixty-six (1.6 per cent) and 23 (0.24 per cent)
      children had visual impairment according to a visual acuity of 6/12 in the worse
      and better eye, respectively. The most common causes of visual impairment were
      refractive errors (81.8 per cent) and amblyopia (14.5 per cent). Among different
      types of refractive errors, astigmatism was the main refractive error leading to
      visual impairment. According to the concentration index, the distribution of
      visual impairment in children from low-income families was higher. CONCLUSION:
      This study revealed a high prevalence of visual impairment in a representative
      sample of seven-year-old Iranian children. Astigmatism and amblyopia were the
      most common causes of visual impairment. The distribution of visual impairment
      was higher in children from low-income families. Cost-effective strategies are
      needed to address these easily treatable causes of visual impairment.

PMID- 29166705
TI  - Comprehensive analysis of nine monoamines and metabolites in small amounts of
      peripheral murine (C57Bl/6 J) tissues.
AB  - Monoamines, acting as hormones and neurotransmitters, play a critical role in
      multiple physiological processes ranging from cognitive function and mood to
      sympathetic nervous system activity, fight-or-flight response and glucose
      homeostasis. In addition to brain and blood, monoamines are abundant in several
      tissues, and dysfunction in their synthesis or signaling is associated with
      various pathological conditions. It was our goal to develop a method to detect
      these compounds in peripheral murine tissues. In this study, we employed a high
      performance liquid chromatography method using electrochemical detection that
      allows not only detection of catecholamines but also a detailed analysis of nine
      monoamines and metabolites in murine tissues. Simple tissue extraction procedures
      were optimized for muscle (gastrocnemius, extensor digitorum longus and soleus),
      liver, pancreas and white adipose tissue in the range of weight 10-200 mg. The
      system allowed a limit of detection between 0.625 and 2.5 pg MUL-1 for monoamine
      analytes and their metabolites, including dopamine, 3,4-dihydroxyphenylacetic
      acid, 3-methoxytyramine, homovanillic acid, norepinephrine, epinephrine, 3
      methoxy-4-hydroxyphenylglycol, serotonin and 5-hydroxyindoleacetic acid. Typical
      concentrations for different monoamines and their metabolization products in
      these tissues are presented for C57Bl/6 J mice fed a high-fat diet.

PMID- 29166706
TI  - [Acute stress response after critical burn].
AB  - The stress response is a preexisting and adaptive behavioral mode of all living
      beings, which may bring deleterious consequences of dysfunction or failure of
      tissue and organ. This article aims to elaborate theories of stress response,
      summarize the manifestation and mechanism of acute stress response in critically
      burned patients, and help to improve clinical curative efficacy and prognosis of
      these patients by physiological, psychological and pharmacological methods.

PMID- 29166707
TI  - [Establishment of myocardial targeted nanoparticles and preliminary evaluation of
      its effects on prevention and treatment of myocardial injury].
AB  - Objective: To establish 3-{4-[2-hydroxyl-(1-methylethylamino) propoxy] phenyl}
      propionic acid cetylesters (PAC) modified nanoparticles, and preliminarily
      explore its cardiomyocyte-targeting function and protection effects on
      myocardium. Methods: (1) HL-1 myocardial cells were divided into cyanidin-3 (Cy3)
      marked non-targeted small interference RNA (Cy3-siNC) group and Cy3 marked small
      interference RNA designed for the nuclear factor kappa B (NF-kappaB)-p65 gene
      (Cy3-si435) group according to the random number table, with 3 wells in each
      group. Cells in Cy3-siNC group were transfected with Cy3-siNC, while cells in Cy3
      si435 group were transfected with Cy3-si435. At transfection hour 24, the mRNA
      expression of NF-kappaB-p65 of cells was determined by real-time fluorescent
      quantitative polymerase chain reaction. (2) Multiple emulsificating solvent
      evaporating method was adopted to prepare PAC modified nanoparticles carried with
      Cy3-siNC (Cy3-siNC-PAC) and PAC modified nanoparticles carried with Cy3-si435
      (Cy3-si435-PAC). The morphology of Cy3-si435-PAC nanoparticles was observed with
      scanning electron microscope, and the size and potential of Cy3-si435-PAC
      nanoparticles were detected by nanometer particle size and zeta potential
      analyzer. The entrapment efficiency and drug loadings of Cy3-si435-PAC
      nanoparticle were determined with ultraviolet spectrophotometer. The release of
      Cy3-si435 of Cy3-si435-PAC nanoparticles was determined by dialysis method. (3)
      Another batch of HL-1 cells were divided into 4 groups according to the random
      number table, with 9 wells in each group. Cells in negative control group were
      added with 5 MUL phosphate buffer. Cells in 25, 50, and 100 mg/mL Cy3-si435-PAC
      nanoparticles groups were added with 5 MUL 25, 50, and 100 mg/mL Cy3-si435-PAC
      nanoparticles, respectively. At transfection hour 6, 12, and 24, proliferation
      activity of cells in 3 wells of each group was detected by methyl thiazolyl
      tetrazolium method, respectively. (4) Another batch of HL-1 cells were cultured
      for 24 h, and then treated with 100 MUL Cy3-si435-PAC nanoparticles. At
      transfection hour 0, 4, 8, 12, and 24, the percentage of cells uptaking Cy3-si435
      PAC nanoparticles in 3 wells were detected by flow cytometry, respectively. (5)
      Another batch of HL-1 cells were divided into 2 groups according to the random
      number table, with 3 wells in each group. Cells in Cy3-siNC-PAC group were added
      with 100 MUL Cy3-siNC-PAC nanoparticles, while cells in Cy3-si435-PAC group were
      added with 100 MUL Cy3-si435-PAC nanoparticles. At transfection hour 24, the mRNA
      expression of NF-kappaB-p65 of cells was determined by real-time fluorescent
      quantitative polymerase chain reaction. (6) Six male C57BL/6J mice were divided
      into 2 groups according to the random number table, with 3 mice in each group.
      Mice in Cy3-siNC-lipopolysaccharide (LPS) group and Cy3-si435-LPS group were
      respectively injected with 500 MUL Cy3-siNC-PAC nanoparticles and Cy3-si435-PAC
      nanoparticles (50 mg/mL) in the tail vein. At injection hour 24, mice in the two
      groups were intraperitoneally injected with 10 mg/kg LPS to induce myocardial
      injury. At post injury hour 24, the distribution of nanoparticles in mice was
      detected with small animal imager. (7) Another 9 male C57BL/6J mice were divided
      into 3 groups according to the random number table, with 3 mice in each group.
      Mice in Cy3-siNC-normal saline (NS) group and Cy3-siNC-LPS group were injected
      with 500 MUL 50 mg/mL Cy3-siNC-PAC nanoparticles in the tail vein, while mice in
      Cy3-si435-LPS group were injected with 500 MUL 50 mg/mL Cy3-si435-PAC
      nanoparticles. At injection hour 24, mice in Cy3-siNC-NS group were
      intraperitoneally injected with NS, while mice in Cy3-siNC-LPS group and Cy3
      si435-LPS group were injected with 10 mg/kg LPS to induce myocardial injury. At
      post injury hour 24, pathological changes of myocardium of mice in each group
      were observed with HE staining. Data were processed with t test and one-way
      analysis of variance. Results: (1) The mRNA expression of NF-kappaB-p65 of cells
      in Cy3-si435 group was 0.183+/-0.004, significantly lower than 1.003+/-0.092 in
      Cy3-siNC group (t=15.46, P<0.01). (2) The form of prepared Cy3-si435-PAC
      nanoparticles was good, with particle size of 146.0 nm, potential of -29.2 mV,
      entrapment efficiency of (86.9+/-1.1) %, drug loadings of (25.4+/-0.9) %, and
      stable Cy3-si435 release. (3) At transfection hour 6, 12, and 24, there were no
      statistically significant differences in proliferation activity of cells in the 4
      groups (with F values from 0.129 to 2.512, P values above 0.05). (4) At
      transfection hour 0, 4, 8, 12, and 24, the percentages of cells uptaking Cy3
      si435-PAC nanoparticles were (0.79+/-0.06)%, (31.04+/-1.59)%, (51.64+/-2.67)%,
      (68.15+/-2.60)%, and (83.68+/-4.67)%, respectively. (5) The mRNA expression of NF
      kappaB-p65 of cells in Cy3-si435-PAC group was 0.286+/-0.015, significantly lower
      than 1.002+/-0.073 in Cy3-siNC-PAC group (t=16.62, P<0.01). (6) At post injury
      hour 24, uniform distribution of nanoparticles could be observed in
      cardiomyocytes of mice in Cy3-siNC-LPS group and Cy3-si435-LPS group. (7) The
      structure of myocardial fibers of mice in Cy3-siNC-NS group was dense, with no
      inflammatory cells infiltration and uniform distribution of cytoplasm. The
      structure of myocardial fibers of mice in Cy3-siNC-LPS group were loose, with
      inflammatory cells infiltration and scattered distribution of cytoplasm. The
      structure of myocardial fibers of mice in Cy3-si435-LPS group was denser, with no
      obvious inflammatory cells infiltration and uniform distribution of cytoplasm.
      Conclusions: Cy3-si435-PAC nanoparticles have good morphology, uniform particle
      size, normal potential distribution, and no cell cytotoxicity. Cy3-si435-PAC
      nanoparticles can be effectively uptaked by HL-1 cells and suppress NF-kappaB-p65
      mRNA expression. They also can effectively target to mice cardiomyocytes to
      reduce inflammatory cells infiltration and alleviate the myocardial injury of
      mice induced by LPS.

PMID- 29166708
TI  - [Effects of astragalus polysaccharide on cardiac dysfunction in rabbits with
      severe scald injury].
AB  - Objective: To investigate the effects of astragalus polysaccharide (AP) on
      cardiac dysfunction in rabbits with severe scald injury. Methods: Sixty-four New
      Zealand white rabbits were divided into pure scald group and AP group according
      to the random number table, with 32 rabbits in each group. Rabbits in the two
      groups were all inflicted with 30% total body surface area full-thickness scald
      on the back. Immediately after injury, rabbits in two groups were
      intraperitoneally injected with lactated Ringer's solution once for antishock.
      Rabbits in AP group were intraperitoneally injected with 10 mL AP solution with
      the dosage of 200 mg/kg 10 min after injury and the following 6 days
      respectively, once a day. Rabbits in pure scald group were injected with 10 mL
      normal saline instead. Eight rabbits of each group were respectively selected
      before injury hour (BIH) 1 and on post injury day(PID) 1, 3, 7, and 14 to collect
      blood samples from ear marginal vein, and then sacrificed immediately to collect
      hearts at each time point post injury. The morphology of myocardium was observed
      after HE staining. The serum content of cardiac troponin I (cTnI) was detected by
      enzyme-linked immunosorbent assay (ELISA). The serum content of aspartate
      transaminase (AST), creatine kinase (CK), CK isoenzyme-MB (CK-MB), lactate
      dehydrogenase (LDH) was detected by fully automatic chemistry analyzer. The
      content of angiotensin II (Ang II) in serum and myocardium was detected with
      radioimmunoassay and the content of endothelin 1 (ET-1) in serum and myocardium
      was detected by ELISA. Another 8 normal rabbits were sacrificed to detect the
      content of Ang II and ET-1 in the myocardium as the value of the two groups of
      scalded rabbits at BIH 1. The serum content of superoxide dismutase (SOD) and
      malondialdehyde (MDA) was detected by ELISA. The values of whole blood viscosity
      (etab), reductive viscosity of whole blood (etar), plasma viscosity (etap),
      hematocrit (HCT), erythrocyte rigidity index (TK), erythrocyte aggregation index
      (EAI), and erythrocyte sedimentation rate (ESR) were detected by fully automatic
      hematology analyzer. Data were processed with analysis of variance of factorial
      design, independent sample t test, and Dunnett test. Results: (1) Compared with
      those in pure scald group, the degrees of cardiomyocyte swelling, steatosis,
      necrosis and rupture of muscle fiber were significantly alleviated in rabbits of
      AP group on PID 1 and 3. There was no obvious increase in cell size, no breakage
      of muscle fiber or infiltration of inflammatory cells in myocardial interstitium
      on PID 7. The myocardial tissue structure and muscle fiber arrangement returned
      to normal condition on PID 14, with no interstitial fibroblast hyperplasia or
      excessive extra cellular matrix deposition. (2) Serum content of cTnI, CK, and
      LDH of rabbits in AP group was significantly lower than that in pure scald group
      on PID 1, 3, and 7 (with t values from 2.69 to 13.99, P<0.05 or P<0.01), while
      there was no significant difference between the two groups on PID 14 (with t
      values from -0.32 to 0.68, P values above 0.05). Serum content of AST and CK-MB
      of rabbits in AP group was significantly lower than that in pure scald group on
      PID 1 and 3 (with t values from 2.21 to 12.65, P<0.05 or P<0.01), while there was
      no significant difference between the two groups on PID 7 and 14 (with t values
      from 0.03 to 1.67, P values above 0.05). (3) Serum content of Ang II of rabbits
      in AP group was significantly lower than that in pure scald group from PID 1 to
      14 (with t values from 3.38 to 32.58, P values below 0.01). Serum content of ET-1
      of rabbits in AP group was significantly lower than that in pure scald group from
      PID 3 to 14 (with t values from 3.54 to 11.02, P values below 0.01), while there
      was no obvious difference on PID 1 (t=0.39, P>0.05). Content of Ang II and ET-1
      in myocardial tissue of rabbits in AP group was significantly lower than that in
      pure scald group from PID 1 to 7 (with t values from 1.27 to 13.79, P values
      below 0.01), while there was no obvious difference on PID 14 (with t values
      respectively 0.07 and 0.81, P values above 0.05). (4) Serum content of SOD of
      rabbits in AP group was respectively (15.65+/-2.64), (14.67+/-0.74), and (8.43+/
      0.56) ng/mL on PID 1, 3, and 7, which was significantly higher than (6.35+/
      0.83), (2.62+/-0.75), and (2.84+/-0.41) ng/mL in pure scald group (with t values
      from -29.79 to -9.10, P values below 0.01); while there was no obvious difference
      on PID 14 [with (4.02+/-0.26) ng/mL in pure scald group and (4.11+/-0.52) ng/mL
      in AP group, t=-0.01, P>0.05]. Serum content of MDA of rabbits in AP group was
      respectively (1.31+/-0.61), (1.72+/-0.64), and (0.65+/-0.42) MUmol /mL on PID 1,
      3, and 7, which was significantly lower than (1.68+/-0.57), (2.34+/-0.79), and
      (1.06+/-0.32) MUmol/mL in pure scald group (with t values from 1.63 to 3.16,
      P<0.05 or P<0.01), while there was no obvious difference on PID 14 [with (0.31+/
      0.09) MUmol/mL in pure scald group and (0.24+/-0.08) MUmol/mL in AP group,
      t=2.11, P>0.05]. (5) Values of etab1 and EAI of rabbits in AP group were
      significantly lower than those in pure scald group from PID 1 to 7 (with t values
      from 2.718 to 11.170, P<0.05 or P<0.01), while there were no obvious differences
      on PID 14 (with t values respectively 2.078 and -1.423, P values above 0.05).
      Values of etab2 and etar2 of rabbits in AP group were significantly lower than
      those in pure scald group on PID 3 and 7 (with t values from 2.178 to 19.205,
      P<0.05 or P<0.01), while there were no obvious differences on PID 1 and 14 (with
      t values from -0.730 to 1.320, P values above 0.05 ). Values of etar1 and ESR of
      rabbits in AP group were significantly lower than those in pure scald group on
      PID 3, 7, and 14 (with t values from 3.021 to 8.058, P values below 0.01), while
      there were no obvious differences on PID 1 (with t values respectively 1.200 and
      1.263, P values above 0.05 ). Value of etap of rabbits in AP group was
      significantly lower than that in pure scald group on PID 1 (t=2.430, P<0.05),
      while there were no obvious differences on PID 3, 7, and 14 (with t values from
      0.002 to 1.446, P values above 0.05 ). Value of HCT of rabbits in AP group was
      close to that in pure scald group on PID 1 (t=1.079, P>0.05), and the values were
      significantly lower than those in pure scald group on PID 3 and 14 (with t values
      respectively 3.849 and 4.208, P values below 0.01), while the value was
      significantly higher than that in pure scald group on PID 7 (t=-4.925, P<0.01).
      Value of TK of rabbits in AP group was lower than that in pure scald group on PID
      7 (t=2.847, P<0.05), while there were no obvious differences on PID 1, 3, and 14
      (with t values from -1.102 to 0.875, P values above 0.05). Conclusions: AP can
      alleviate the damage of myocardium of rabbits with severe scald by reducing the
      production of vasoactive substances Ang II and ET-1, decreasing oxidative stress
      injury by increasing the content of SOD and decreasing the production of MDA,
      improving blood flow performance and microcirculation perfusion.

PMID- 29166709
TI  - [Effects of dexmedetomidine on myocardium of rats with severe burn at early
      stage].
AB  - Objective: To investigate the effects of dexmedetomidine on myocardium of rats at
      early stage after severe burn. Methods: Twenty specific pathogen free male SD
      rats were immersed in 90 C hot water for 20 s, causing 30% total body surface
      area (TBSA) full-thickness scald (hereafter referred to as burn) on the back. And
      then they were divided into burn resuscitation group (BR) and burn resuscitation+
      dexmedetomidine group (BRD) according to the random number table, with 10 rats in
      each group. Sodium lactate Ringer's solution (2 mL.kg(-1).%TBSA(-1)) were
      intraperitoneally injected into rats of both groups after burn. Dexmedetomidine
      with dose of 1 MUg/kg was intraperitoneally injected into rats of group BRD at
      the same time point. Another 5 rats in sham injury group (SI) were immersed in 37
      C water bath causing sham injury, and fluid resuscitation of rats in group SI was
      the same as that in group BR. Five rats of group BR and BRD were respectively
      selected at post burn hour (PBH) 6 and 24. And then left ventricular end-systolic
      internal diameter (LVIDs), left ventricular end-diastolic internal diameter
      (LVIDd), ejection fraction (EF), and cardiac output (CO) were determined with
      small animal ultrasonic imaging system. Plasma levels of cardiac troponin (cTn) I
      and cTnT were detected by enzyme-linked immunosorbent assay, and morphological
      changes of myocardium were observed under optical microscope and transmission
      electron microscope (observed only at PBH 24). In rats of group SI, morphological
      change of myocardium was observed at PBH 24, and the other indexes were detected
      as above. Data were processed with one-way analysis of variance and SNK test.
      Results: At PBH 6, EF value of rats in group BR [(98.0+/-2.8) %] was obviously
      higher than that in group SI [(91.0+/-0.4)%, P<0.05]. The other 3 cardiac
      ultrasound indexes of rats in group BR were close to those in group SI (with P
      values above 0.05). Each cardiac ultrasound index of rats between groups BRD and
      SI was close at PBH 6 (with P values above 0.05). At PBH 24, LVIDs levels of rats
      in group BR [(0.66+/-0.59) mm] and group BRD[(0.69+/-0.27) mm] were obviously
      lower than LVIDs level of rats in group SI [(1.65+/-0.33) mm, with P values below
      0.05]. LVIDd, EF, and CO levels of rats were close among 3 groups at PBH 24 (with
      P values above 0.05). At PBH 6, the plasma levels of cTnI [(17.40+/-1.59) ng/mL]
      and cTnT [(1 488+/-229) pg/mL] of rats in group BR were significantly higher than
      those in group SI [(1.84+/-0.92) ng/mL and (169+/-12) pg/mL, with P values below
      0.01]. At PBH 6 in group BRD, the plasma level of cTnI of rats [(2.58+/-0.60)
      ng/mL] was close to that in group SI (P>0.05), and the plasma level of cTnT
      [(649+/-190) pg/mL] was higher than that in group SI (P<0.01). At PBH 24, the
      plasma levels of cTnI and cTnT of rats in group SI were close to those in groups
      BR and BRD (with P values above 0.05). At PBH 24, the plasma level of cTnI of
      rats in group BRD was obviously lower than that in group BR (P<0.01). At PBH 6,
      the myocardial structures of rats in group BR and group BRD were normal, which
      were close to myocardial structure of rats in group SI at PBH 24. At PBH 24,
      obviously damaged myocardial tissue, disorderly arrangement of myofilament, and
      seriously damaged mitochondria were observed in rats of group BR, which were
      significantly ameliorated in rats of group BRD. Conclusions: Dexmedetomidine can
      protect the myocardium of rats with severe burn at early stage.

PMID- 29166711
TI  - [Effects of caspase-1 inhibitor VX765 on cold-restraint stress-induced acute
      gastric ulcer in mice].
AB  - Objective: To investigate the protective effects of caspase-1 inhibitor VX765 on
      gastric mucosa of mice with cold-restraint stress-induced acute gastric ulcer.
      Methods: Twenty-four specific pathogen free male C57BL/6J mice were divided into
      normal control group (NC), cold restrain group (CR), VX765 pre-treatment+ cold
      restrain group (VCR), and rabeprazole pre-treatment+ cold restrain group (RCR)
      according to the random number table, with 6 mice in each group. Mice in group NC
      were injected intraperitoneally with solution of 10 mL/kg dimethylsulfoxide
      (DMSO) and phosphate buffer solution (PBS). Mice in group CR were inflicted with
      acute gastric ulcer induced by cold-restraint stress 30 minutes after
      intraperitoneal injection of solution of DMSO and PBS. Mice in groups VCR and RCR
      were inflicted with acute gastric ulcer as above 30 minutes after intraperitoneal
      injection of solution of DMSO and PBS with dose of 12.5 MUmol/kg containing 10 mg
      VX765 and 40 mg/kg containing 20 mg rabeprazole, respectively. Four hour after
      cold-restraint stress, serum content of tumor necrosis factor alpha (TNF-alpha)
      and interleukin 6 (IL-6)was determined by enzyme-linked immunosorbent assay.
      Gross condition of gastric tissue was observed. Ulcer index was evaluated.
      Pathological change of gastric tissue was observed with HE staining. The relative
      expression of IL-1beta, IL-18, and cleaved-caspase-1 in gastric tissue were
      detected by Western blotting. Mice in group NC were detected as above at the same
      time point. Data were processed with one-way analysis of variance and Bonferroni
      test. Results: The serum content of TNF-alpha and IL-6 and the relative
      expression of cleaved-caspase-1, IL-1beta, and IL-18 in gastric tissue of mice in
      group NC were significantly lower than those in group CR (with P values below
      0.01). The content of the above-mentioned inflammatory indexes in serum and
      gastric tissue of mice in group VCR was significantly lower than that in group CR
      (with P values below 0.01). There were no statistically significant differences
      in content of the above-mentioned inflammatory indexes in serum and gastric
      tissue of mice between groups RCR and CR (with P values above 0.05). The content
      of the above-mentioned inflammatory indexes in serum and gastric tissue of mice
      in group VCR was significantly lower than that in group RCR (with P values below
      0.01). Surface of gastric mucosa was smooth and morphology of mucosal cells was
      normal with clear structure of mice in group NC. Multiple hemorrhage of gastric
      mucosa, disorderly arrangement of mucosal cells, and large number of inflammatory
      cell infiltration around necrotic tissue were observed in mice of group CR.
      Decreased number of gastric mucosa bleeding, intact mucosal structure, and small
      amount of inflammatory cell infiltration around necrotic tissue were observed in
      mice of groups VCR and RCR. The ulcer indexes of mice in groups NC, CR, VCR, and
      RCR were 0, 18.7+/-1.1, 6.3+/-1.5, and 8.2+/-1.3, respectively. The ulcer index
      of mice in group NC was significantly lower than that in the other 3 groups (with
      P values below 0.05). The ulcer indexes of mice in groups VCR and RCR were close
      (P>0.05), which were significantly lower than ulcer index of mice in group CR
      (with P values below 0.05). Conclusions: VX765 can effectively inhibit the
      activation of caspase-1, reduce production of inflammatory factor, and alleviate
      inflammatory response, which have protective effects on gastric mucosa of mice
      with cold-restraint stress-induced acute gastric ulcer.

PMID- 29166710
TI  - [Effects of hydrogen on the lung damage of mice at early stage of severe burn].
AB  - Objective: To investigate the effects of hydrogen on the lung damage of mice at
      early stage of severe burn. Methods: One hundred and sixty ICR mice were divided
      into sham injury, hydrogen, pure burn, and burn+ hydrogen groups according to the
      random number table, with 40 mice in each group. Mice in pure burn group and
      burn+ hydrogen group were inflicted with 40% total body surface area full
      thickness scald (hereafter referred to as burn) on the back, while mice in sham
      injury group and hydrogen group were sham injured. Mice in hydrogen group and
      burn+ hydrogen group inhaled 2% hydrogen for 1 h at post injury hour (PIH) 1 and
      6, respectively, while mice in sham injury group and pure burn group inhaled air
      for 1 h. At PIH 24, lung tissue of six mice in each group was harvested, and then
      pathological changes of lung tissue were observed by HE staining and the lung
      tissue injury pathological score was calculated. Inferior vena cava blood and
      lung tissue of other eight mice in each group were obtained, and then content of
      high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) in serum and lung
      tissue was determined by enzyme-linked immunosorbent assay. Activity of
      superoxide dismutase (SOD) in serum and lung tissue was detected by
      spectrophotometry. After arterial blood of other six mice in each group was
      collected for detection of arterial partial pressure of oxygen (PaO(2)), the wet
      and dry weight of lung tissue were weighted to calculate lung wet to dry weight
      ratio. The survival rates of the other twenty mice in each group during post
      injury days 7 were calculated. Data were processed with one-way analysis of
      variance, LSD test and log-rank test. Results: (1) At PIH 24, lung tissue of mice
      in sham injury group and hydrogen group showed no abnormality. Mice in pure burn
      group were with pulmonary interstitial edema, serious rupture of alveolar
      capillary wall, and infiltration of a large number of inflammatory cells. Mice in
      burn+ hydrogen group were with mild pulmonary interstitial edema, alveolar
      capillary congestion accompanied by slight rupture and bleeding, and the number
      of infiltration of inflammatory cells was smaller than that in pure burn group.
      The lung tissue injury pathological scores of mice in sham injury group, hydrogen
      group, pure burn group, and burn+ hydrogen group were (0.7+/-0.5), (0.8+/-0.5),
      (6.1+/-1.0), and (2.8+/-0.8) points, respectively. The lung tissue injury
      pathological score of mice in pure burn group was significantly higher than that
      in sham injury group (P<0.001). The lung tissue injury pathological score of mice
      in burn+ hydrogen group was significantly lower than that in pure burn group
      (P<0.001). (2) At PIH 24, the content of HMGB1 and IL-6 in serum and lung tissue
      of mice in hydrogen group was close to that in sham injury group (with P values
      above 0.05). The content of HMGB1 and IL-6 in serum and lung tissue of mice in
      pure burn group was significantly higher than that in sham injury group (with P
      values below 0.001). The content of HMGB1 and IL-6 in serum and lung tissue of
      mice in burn+ hydrogen group was significantly lower than that in pure burn group
      (with P values below 0.001). (3) At PIH 24, the activity of SOD in serum and lung
      tissue of mice in hydrogen group was close to that in sham injury group (with P
      values above 0.05). The activity of SOD in serum and lung tissue of mice in pure
      burn group was significantly lower than that in sham injury group (with P values
      below 0.001). The activity of SOD in serum and lung tissue of mice in burn+
      hydrogen group was significantly higher than that in pure burn group (with P
      values below 0.001). (4) At PIH 24, there was no statistically significant
      difference in PaO(2) among the mice in four groups (F=0.04, P>0.05). (5) At PIH
      24, the ratios of lung wet to dry weight of mice in sham injury, hydrogen, pure
      burn, and burn+ hydrogen groups were 3.52+/-0.22, 3.61+/-0.24, 7.24+/-0.32, and
      5.21+/-0.41, respectively. The ratio of lung wet to dry weight of mice in pure
      burn group was significantly higher than that in sham injury group (P<0.001). The
      ratio of lung wet to dry weight of mice in burn+ hydrogen group was significantly
      lower than that in pure burn group (P<0.001). (6) The survival rates of mice in
      sham injury group and hydrogen group during post injury days 7 were 100%.
      Compared with those in sham injury group, survival rates of mice in pure burn
      group from post injury days 3 to 7 were significantly decreased (with P values
      below 0.05). Compared with those in pure burn group, survival rates of mice in
      burn+ hydrogen group from post injury days 5 to 7 were significantly increased
      (with P values below 0.05). Conclusions: Hydrogen can significantly alleviate the
      infiltration of inflammatory cells and improve the pathological lesions of lung
      tissue of mice with severe burn. It has the effects of reducing inflammatory
      reaction and inhibiting oxidative stress, further showing the protective effect
      on the lung of burn mice.

PMID- 29166712
TI  - [Effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the
      mechanisms].
AB  - Objective: To explore the effects of endostatin pretreatment on fibrosis of human
      skin fibroblasts and the mechanisms. Methods: Human skin fibroblasts were
      routinely cultured in vitro, and then the cells of passage 3 to 5 were used in
      the following experiments. The cells were divided into blank control, endostatin,
      platelet-derived growth factor-BB (PDGF-BB), endostatin+ PDGF-BB, transforming
      growth factor-beta(1) (TGF-beta(1)), and endostatin+ TGF-beta(1) groups according
      to the random number table, with 3 wells in each group. Cells in blank control
      group were cultured with DMEM medium for 24 h. Cells in endostatin group were
      cultured with DMEM medium containing 5 MUg/mL endostatin for 24 h. Cells in PDGF
      BB group and TGF-beta(1) group were cultured with DMEM medium containing 200
      ng/mL PDGF-BB and 10 ng/mL TGF-beta(1) for 24 h, respectively. Cells in
      endostatin+ PDGF-BB group were pretreated with DMEM medium containing 5 MUg/mL
      endostatin for 48 h and then cultured with DMEM medium containing 200 ng/mL PDGF
      BB for 24 h. Cells in endostatin+ TGF-beta(1) group were pretreated with DMEM
      medium containing 5 MUg/mL endostatin for 48 h and then cultured with DMEM medium
      containing 10 ng/mL TGF-beta(1) for 24 h. The content of type I collagen in the
      cell culture supernatant of three wells in each group was determined by enzyme
      linked immunosorbent assay. The protein expression levels of alpha-smooth muscle
      actin (alpha-SMA), PDGF receptor beta (PDGFRbeta), phosphorylated PDGFRbeta (p
      PDGFRbeta), and phosphorylated extracellular signal-regulated protein kinases 1/2
      (p-ERK1/2) of three wells in each group were detected by Western blotting. Data
      were processed with one-way analysis of variance and SNK test. Results: (1)
      Compared with (5.05+/-0.29) pg/mL in blank control group, content of type I
      collagen in the cell culture supernatant of endostatin group [(4.72+/-0.37)
      pg/mL] was close to it (P>0.05), content of type I collagen in the cell culture
      supernatant of PDGF-BB group and TGF-beta(1) group [(8.60+/-0.57) and (9.20+/
      0.64) pg/mL, respectively] was higher (with P values below 0.05). Content of type
      I collagen in the cell culture supernatant of endostatin+ PDGF-BB group [(5.32+/
      0.17) pg/mL] was lower than that of PDGF-BB group (P<0.05), and content of type I
      collagen in the cell culture supernatant of endostatin+ TGF-beta(1) group
      [(5.41+/-0.20) pg/mL] was lower than that of TGF-beta(1) group (P<0.05). (2)
      Compared with those in blank control group, protein expression levels of alpha
      SMA, PDGFRbeta, p-PDGFRbeta, and p-ERK1/2 of cells in endostatin group showed no
      obvious differences (with P values above 0.05), while those in PDGF-BB and TGF
      beta(1) group were significantly higher (with P values below 0.01). Protein
      expression levels of alpha-SMA, PDGFRbeta, p-PDGFRbeta, and p-ERK1/2 of cells in
      endostatin+ PDGF-BB group and endostatin+ TGF-beta(1) group were significantly
      lower than those in PDGF-BB group and TGF-beta(1) group, respectively (with P
      values below 0.05). Conclusions: Pretreatment of endostatin can inhibit the
      fibrosis of human skin fibroblast and its transformation into myofibroblast,
      which may be related to the down-regulation of protein expression of p-PDGFRbeta,
      PDGFRbeta, and p-ERK.

PMID- 29166714
TI  - [New perspectives on the role of atrial myopathy in the pathogenesis of atrial
      fibrillation].

PMID- 29166713
TI  - [Advances in the research of molecular mechanism of negative pressure wound
      therapy in improving wound healing].
AB  - Recently, negative pressure wound therapy (NPWT) is a rising technology to
      improve wound healing. In clinical application, it benefits fast debridement and
      wound close, limits infection, and promotes wound healing. It is an effective
      therapy for all kinds of acute or chronic wound. Currently, researches
      demonstrate that NPWT promotes angiogenesis, granulation tissue growth, and
      extracellular matrix remodeling through regulating the signaling of anti
      inflammatory cytokines, mechanicalreceptor and chemoreceptor, which is related to
      several growth factors and inflammatory factors. Here we focus on the recent
      advances in the mechanism of NPWT in promoting wound healing, looking forward to
      providing a review of NPWT and related researches.

PMID- 29166715
TI  - [Left atrial appendage closure for stroke prevention: controversies and
      considerations].

PMID- 29166716
TI  - [Current status of the long-term adherence to warfarin anticoagulation therapy in
      patients with non-valvular atrial fibrillation].

PMID- 29166717
TI  - [Left atrial appendage volume is a valuable predictor of atrial fibrillation
      recurrence after radiofrequency catheter ablation].
AB  - Objective: To investigate the association between the left atrial appendage (LAA)
      volume and atrial fibrillation (AF) recurrence after radiofrequency catheter
      ablation. Methods: We prospectively enrolled sixty-two patients with AF (40 cases
      with paroxysmal AF, 22 cases with persistent AF) who successfully underwent a
      first AF catheter ablation and had performed contrast-enhanced cardiac computed
      tomography (CT) prior to the procedure to measure LAA volumes in our hospital
      from January 2012 to August 2015. Circumferential pulmonary vein isolation was
      performed under the guidance of three-dimension mapping system (CARTO system).
      Linear ablation or ablation of complex fractioned atrial electrograms was also
      undertaken if necessary. All patients were followed up at the 3rd, 6th and 12th
      months after ablation by 24-hour ambulatory Holter monitoring, and were divided
      into the non-recurrence group (n=42) and the AF recurrence group (n=20).
      Univariate and multivariate Cox proportional hazards regression analysis were
      used to assess the factors related to AF recurrence. The receiver operating
      characteristic (ROC) curve was calculated to assess the best cut-off value of LAA
      volume to predict AF recurrence. Kaplan-Meier method was used to evaluate the
      rate of freedom from AF recurrence. Results: Mean LAA volume in all patients was
      (9.5+/-3.6)ml. AF recurrence occurred in 20 patients (32%) during the follow-up
      period. The LAA volume was significantly larger in the AF recurrence group than
      in the non-recurrence group ((11.5+/-3.8)ml vs. (8.3+/-3.1)ml, P=0.002). In the
      univariate regression analysis, LAA volume (HR=1.36, 95%CI 1.14-1.82, P<0.001),
      persistent AF (HR=4.43, 95%CI 1.52-12.06, P<0.001) and hypertension (HR=1.61,
      95%CI 1.13-2.04, P=0.041) were risk factors of AF recurrence. However,
      multivariate regression analysis revealed that LAA volume (HR=1.32, 95%CI 1.12
      1.51, P<0.001) and persistent AF (HR=4.22, 95% CI 1.48-11.05, P<0.001) were
      independent predictors for AF recurrence after ablation. The receiver operating
      characteristic (ROC) curve analysis revealed that a LAA volume >8.80 ml was
      associated with AF recurrence after ablation (sensitivity: 94% and specificity:
      66%, area under the curve=0.76). Kaplan-Meier analysis showed a lower rate free
      from AF recurrence in the group with LAA volume >8.80 ml (P<0.001). Conclusion:
      Larger LAA volume is associated with AF recurrence after catheter ablation in
      patients with AF. A LAA volume greater than 8.80 ml could be used to predict AF
      recurrence after ablation.

PMID- 29166718
TI  - [Value of two left atrium and pulmonary vein stereoscopic imaging reconstruction
      methods on guiding radiofrequency ablation for atrial fibrillation].
AB  - Objective: To compare the value of two 3D imaging reconstruction methods for left
      atria and pulmonary vein on guiding the catheter ablation for atrial fibrillation
      (AF). Methods: From January 2014 to January 2017, a total of 100 drug refractory
      paroxysmal AF patients were divided into left atria direct angiography group
      (n=50), and indirect angiography group (n=50). 3D CARTO system was applied for
      mapping and guiding the ablation procedure. Patients assigned to direct
      angiography group were treated as follows: intraoperative puncture of atrial
      septum, inject contrast agent directly into the left atrium, conduct left atrial
      and pulmonary venous rotation angiography, reconstruct three-dimensional image,
      integrate the image into real-time X-ray system to facilitate circumferential
      pulmonary vein isolation. Patients assigned into the indirect angiography group
      were treated as follows: inject contrast agent through the right ventricle,
      conduct delayed rotation angiography of the left atria and pulmonary vein to
      guide circumferential pulmonary vein fixation and ablation. The left atrial and
      pulmonary venous image acquisition, the operation and X-ray exposure time, the
      success rate and the incidence of complication of the two groups were compared.
      The patients were followed up for 3-6 months. Results: General clinical
      characteristics of the two groups were similar(all P>0.05). Ablation was
      successful in all 100 patients. The operation time[(112.0+/-21.4)min vs. (134.0+/
      24.3)min]and X-ray exposure time((10.7+/-4.7)min vs. (15.8+/-5.2)min)were
      significantly lower in direct angiography group than in indirect angiography
      group (both P<0.01). There was no significant difference between the two groups
      in the immediate (86%(43/50) vs. 82%(41/50), P=0.59) and short-term (76%(38/50)
      vs. 72%(36/50), P=0.65) success rate and complication rate (1 aneurysm in the
      direct angiography group, 1 pericardial tamponade in the indirect angiography
      group). In-hospital mortality was zero percent. Conclusion: It is safe and
      effective method to guide the radiofrequency catheter ablation of paroxysmal
      atrial fibrillation by reconstruction 3D image of left atrium and pulmonary vein.
      Compared with indirect angiography group, direct angiography group can improve
      the imaging quality of left atrium and pulmonary vein, decrease the X-ray
      exposure time of the ablation procedure.

PMID- 29166719
TI  - [Clinical characteristics and outcome comparison between atrial fibrillation
      patients underwent catheter ablation under general aesthesia or local anesthesia
      and sedation].
AB  - Objective: To compare the outcome of radiofrequency catheter ablation under local
      anesthesia/sedation (S) or general anesthesia(GA) in atrial fibrillation
      patients. Methods: Data of 498 patients with atrial fibrillation undergoing
      radiofrequency catheter ablation in our departmentfrom January 2014 to December
      2015 were retrospectively analyzed. Two hundred and twenty patients assigned to
      the GA group, the other 278 patients to the S group. Patients were followed
      clinically every 3 months within one year after procedure. Immediate
      electrocardiogram was performed in patients with palpitation or choking sensation
      in chest. The end point of the study was recurrence of any atrial tachyarrhythmia
      lasting >30 seconds in device interrogation, 24-hour Holter monitoring or 12-lead
      electrocardiogram after a single procedure. After the ablation procedure, a
      blanking period of 3 months was allowed according to the guidelines. Procedure
      time, radiofrequency time, fluoroscopy time, the detection of paroxysmal
      supraventricular tachycardia, the success rate and the complications were
      compared between the two groups. Results: There was no difference in the baseline
      characteristics between the two groups, such as age, gender, BMI, complications,
      LVEF, LAD (all P>0.05). The duration of procedure ((117.8+/-51.7)minutes
      vs.(115.4+/-36.9)minutes, P=0.79), duration of fluoroscopy((12.5+/-11.2)minutes
      vs. (10.4+/-10.2)minutes, P=0.35), duration of radiofrequency((40.1+/
      12.9)minutes vs. (48.6+/-44.3)minutes, P=0.48) were similar between the two
      groups (P>0.05). Compared with S group, discovery of the frequency of
      atrioventricular node reentrant tachycardia (AVNRT) was significantly lower in GA
      group (0 vs. 3.6%(10/278), P<0.01), but the difference disappeared with repeat
      electrophysiological examination when patients become conscious from
      GA(3.2%(7/220) vs. 3.6%(10/278), P=0.311). The difference of atrioventricular
      reentrant tachycardia (AVRT) was similar between the two groups(0.9%(2/220) vs.
      0.7%(2/278), P=0.841). Compared with S group, reflection of vagus nerve was less
      in GA group (1.4%(3/220) vs. 8.6%(24/278), P=0.026). After following up of (356+/
      92) days, freedom from atrial fibrillation/atrial flutter/atrial tachyarrhythmia
      was similar between the two groups(77.9%(162/208) vs. 79.9%(215/269), P=0.818).
      Conclusion: General anesthesia is a promising method to atrial fibrillation
      ablation, in view of stable patient status and safety for the procedure. There is
      no difference in complications, recurrence of arrhythmia between the two groups,
      but detection rate of AVNRT is lower in GA group.

PMID- 29166720
TI  - [Long term safety and efficacy of a novel abluminal groove-filled biodegradable
      polymer sirolimus-eluting stent for the treatment of coronary de novo lesions].
AB  - Objective: To compare the long term safety and efficacy of the novel abluminal
      groove-filled biodegradable polymer sirolimus-eluting stent(Firehawk stent) and
      permanent polymer coating everolimus eluting stent(Xience V stent) for the
      treatment of coronary de novo lesions. Methods: This prospective, multi-center,
      non-inferiority, randomized control trial(TARGETI trial) was performed between
      August 2010 and April 2011, a total of 460 patients with primary, de novo, single
      vessel and single coronary lesion from 16 medical centers were enrolled. The
      diameter stenosis of target lesion was >=70%, and lesion length was<=24 mm. The
      patients were randomly assigned to treatment with Firehawk stent (Firehawk stent
      group) or Xience V stent (Xience V stent group) groups by a web-based allocation
      system and was stratified by center. The late lumen loss after 9 months, target
      lesion failure (TLF) which was a composite of cardiac death, target vessel
      myocardial infarction, or ischemia driven target lesion revascularization,
      patient-oriented composite endpoint (PoCE) which was a composite of all cause
      death, all cause myocardial infarction, or any revascularization, and stent
      thrombosis after 5 years were compared between the two groups. Results: (1) There
      were 2 patients without stent implantation dropped out of this trial. There were
      227 patients in Firehawk stent group, and 231 patients in Xience V stent group.
      The baseline characteristics were similar between the two groups(all P>0.05). (2)
      The 9 months late lumen loss in Firehawk stent group was non-inferior to that in
      Xience V stent group ((0.13+/-0.24)mm vs. (0.13+/-0.18)mm, P=0.94). (3) A total
      of 442 (96.5%) patients completed 5 years clinical follow-up. There were no
      significant differences on 5-year TLF rate (6.0%(13/217) vs. 6.7% (15/225),
      P=0.77) and PoCE rate (12.0%(26/217) vs. 17.8% (40/225), P=0.09) between the
      Firehawk stent group and Xience V stent group. (4) Kaplan-Meier analysis showed
      that TLF rates between 1-5 years were similar in Firehawk stent group and Xience
      V stent group (5.7% and 6.6% respectively, HR=0.88, 95%CI 0.42-1.84, P=0.72).
      Land-Mark analysis showed that TLF rates bewteen 1-5 years were similar in
      Firehawk stent group and Xience V stent group (3.6% and 4.4% respectively,
      HR=0.83, 95%CI 0.34-2.00, P=0.67). Kaplan-Meier analysis showed that PoCE rates
      between 1-5 years were also similar in Firehawk stent group and Xience V stent
      group (11.4% and 17.3% respectively, HR=0.64, 95%CI 0.39-1.04, P=0.07). Land-Mark
      analysis showed that PoCE rates after 5 years were similar in Firehawk stent
      group and Xience V stent group (8.4% and 10.0% respectively, HR=0.66, 95%CI 0.40
      1.10, P=0.11). (5) No stent thrombosis was documented in Firehawk stent group
      during the 5 years follow-up period, and there was 1 case of stent thrombosis in
      Xience V stent group after 3 years of stent implantation. Conclusion: TARGETI
      trial results of 5 years follow up indicate the novel Firehawk stent have a
      durable safety and efficacy profile which is comparable to the Xience V stent in
      treating patients with single de novo coronary lesion. Clinical Trial
      Registration North American Clinical Trial Registration Center, NCT01196819.

PMID- 29166721
TI  - [A preliminary study on the relationship between idiopathic arrhythmia and
      cardiac magnetic resonance imaging defined cardiac features in patients with
      straight back syndrome].
AB  - Objective: To retrospectively analyze the potential correlation between cardiac
      magnetic resonance (CMR) imaging and clinical features and idiopathic arrhythmia
      in patients with straight back syndrome (SBS). Methods: Patients receiving CMR
      imaging examination from April 2015 to March 2016 at our department (n=1 432)
      were screened, 76 patients met the diagnosis criteria of flat chest
      (anteroposterior diameter/transthoracic diameter (APD/TTD) ratio<0.37 at the T8
      vertebra). After excluding 33 patients with structural heart disease, 43 SBS
      patients were divided into two groups: SBS without obvious morphological change
      in the heart (group A, n=19) and SBS with morphological change of the heart
      (group B, n=24). CMR images were analyzed, focusing the heart morphological
      changes induced by SBS. The clinical data were collected to comprehensively
      analyze the medical history, electrocardiogram and electrophysiological
      examination in order to observe the relationship between SBS induced heart
      morphological change and the arrhythmia type and origin. Results: There were 21
      male patients in this cohort, mean age was (28.5+/-11.5) years (13-58 years).
      APD/TTD ratio was similar between the two groups (0.30+/-0.03 vs. 0.29+/-0.04,
      P>0.05). LVEF tended to be lower in group B than in group A ((47.48+/-12.77)%vs.
      (59.31+/-9.04)%, P>0.05) . In group B, there were 15 patients with left
      ventricular enlargement, 2 with left ventricular wall thickening, 5 with
      uncoordinated ventricular wall motion, 5 with tricuspid regurgitation, 3 with
      mitral regurgitation, 2 with myocardial fibrosis, 5 with increased trabecular and
      16 with decreased left ventricular function. Direct compression sign of right
      ventricle (disappeared precordial fat tissue space, secondary right atria
      enlargement and tricuspid regurgitation) and left atria (with or without
      secondary left ventricular enlargement and mitral regurgitation) were evidenced
      in patients of group B. CMR revealed that the arrhythmia origin corresponded the
      compression site of the heart in 8 cases (42.1%) in group A and 13 cases (54.2%)
      in group B, not corresponded to the compression site in 6 patients (31.6%) in
      group A and in 7 patients (29.2%) in group B, not attributable in 5 patients
      (26.3%) in group A and 4 patients (16.7%) in group B. The percent of arrhythmia
      origin corresponded the compression site of the heart tended to be higher in
      group B as compared to group A (P>0.05). Conclusion: SBS can induce changes of
      cardiac morphology and cardiac function. SBS induced cardiac compression is
      linked with the development of arrhythmias and might be one of the reasons of
      arrhythmias in these patients.

PMID- 29166722
TI  - [Value of bedside echocardiography in diagnosis and risk assessment of in
      hospital death for patients with Stanford type A aortic dissection].
AB  - Objective: To investigate the value of bedside echocardiography in diagnosis and
      risk assessment of in-hospital death of patients with Stanford type A aortic
      dissection. Methods: The clinical data of 229 patients with Stanford type A
      aortic dissection diagnosed by CT angiography in Zhongshan Hospital affiliated to
      Fudan University between January 2009 and January 2016 were retrospectively
      analyzed. The patients were divided into survival group(191 cases)and non
      survival group(38 cases)according to presence or absence of in-hospital death.
      The bedside echocardiography features were analyzed, and influence factors of in
      hospital death were determined by multivariate logistic regression analysis.
      Results: (1) Compared with the survival group, the non-survival group had lower
      surgery rate (60.52%(23/38) vs. 85.34%(163/191), P<0.01). Age, gender and Debakey
      classification were similar between survival group and death group (all P>0.05).
      (2) The bedside echocardiography results showed that prevalence of aortic valve
      involvement(65.79%(25/38) vs.34.03%(65/191), P<0.01) and severe aortic
      regurgitation (44.74%(17/38) vs. 14.14%(27/191), P<0.01) were significantly
      higher in non-survival group than in survival group. The non-survival group had
      larger aortic root diameter than the survival group ((55.5+/-6.4)mm vs. (42.3+/
      7.8)mm, P<0.01). There were no significant differences in pericardial effusion,
      expansion of aortic sinus, and left ventricular ejection fraction between
      survival group and non-survival group (all P>0.05). (3) The multivariate logistic
      regression analysis showed that aortic valve involvement(OR=3.275, 95%CI 1.290
      8.313, P<0.05), aortic root diameter(OR=1.202, 95%CI 1.134-1.275, P<0.01), and
      surgery (OR=0.224, 95%CI 0.079-0.629, P<0.01) were independent risk factors for
      in-hospital death in patients with Stanford type A aortic dissection.
      Conclusions: Bedside echocardiography has significant diagnostic value for
      Stanford type A aortic dissection. Aortic valve involvement, enlargement of
      aortic root diameter and without surgery are independent risk factors for
      patients with Stanford type A aortic dissection.

PMID- 29166723
TI  - [Association between serum Nepsilon-carboxymethyl-lysine level and anterior
      tibial arterial plaque calcification in patients with diabetic foot post foot
      amputation].
AB  - Objective: To observe the correlation between Nepsilon-carboxymethyl-Lysine
      (CML), the main component of advanced glycation end products and the
      calcification of the anterior tibial artery plaque in patients with diabetic foot
      post foot amputation. Methods: Sixty patients hospitalized for foot amputation
      operation due to diabetic foot from June 2012 to June 2016 in the Department of
      Orthopedics, Affiliated Hospital of Jiangsu University were prospectively
      recruited.The patients were categorized into mild stenosis (0<stenosis<50%,
      n=20), moderate stenosis (50%<=stenosis<70%, n=20) and severe stenosis
      (70%<=stenosis<=100%, n=20) based on the color Doppler ultrasound assessed
      severity of anterior tibial artery stenosis.The baseline clinical data of
      patients were collected and anterior tibial artery was isolated.Then, HE
      staining, O-Cresolphthalein Complexone method, enzymic method and ELASA analysis
      were then performed to detect the evolution of calcification, arterial calcium
      content, alkaline phosphatase activity and serum CML concentration, respectively.
      Results: The results from both color Doppler ultrasound scan before amputation
      and HE staining after amputation showed that echo intensity as well as spotty
      blue calcium particles of anterior tibial artery plaque increased significantly
      in proportion to degree of stenosis and destructed elastic plate of the arterial
      wall was evidenced in patients with severest stenosis.The content of calcium
      ((2.3+/-0.9), (3.9+/-1.3), (6.6+/-1.7) MUmol/mg, respectively, P<0.001), ALP
      activity ((102.4+/-39.4), (202.3+/-73.4), (483.7+/-117.9) U/mg, respectively,
      P<0.001) and serum CML level ((28.9+/-4.4), (37.9+/-5.3), (57.3+/-7.1)MUg/L,
      respectively, P<0.001) increased significantly in proportion to stenosis
      severity.Pearson correlation analysis showed that serum CML level was positively
      correlated with the content of calcium (r=0.749, P<0.001) and ALP activity
      (r=0.923, P<0.001), respectively. Conclusions: Serum CML level is positively
      correlated with the calcification of anterior tibial arterial plaque in patients
      with diabetic foot and could be used to evaluate the calcification of anterior
      tibial arterial plaque and stenosis degree of anterior tibial arterial in these
      patients.

PMID- 29166724
TI  - [Beneficial effects of Schisandrin B on the cardiac structure and function in a
      mice model of myocardial infarction].
AB  - Objective: To investigate whether Schisandrin B (Sch B) could improve cardiac
      structure and function in myocardial infarction (MI) mice and related mechanisms.
      Methods: Male C57BL/6J mice were randomized into sham (n=8), MI+ Sch B (n=24, 80
      mg.kg(-1).d(-1) per gavage) or MI+ vehicle (n=24, equal volume). After treatment
      for 3 weeks, cardiac function was detected by echocardiography
      measurement.Infarction size was measured by Evans blue and TTC staining.HE and
      Masson trichrome staining were used to observe the myocardial inflammation,
      structure and fibrosis.TNF-alpha, TGF-beta, IL-1beta were detected by ELISA. The
      apoptosis index of ischemic myocardial cells was detected by immunofluorescence.
      NF-kappaB, Bcl-2, Bax, Akt phosphorylated Akt(p-Akt), eNOS, phosphorylated eNOS
      (p-eNOS) were detected by Western blot. Results: Three weeks after operation,
      survival rate (83.33% vs. 54.17%, P<0.05), LVEF((51.77+/-8.50)% vs.(40.23+/
      8.30)%, P<0.05), LVFS((26.44+/-5.15)% vs. (19.53+/-4.56)%, P<0.05)were
      significantly higher; LVEDD ((4.13+/-0.40) mm vs.(4.44+/-0.46)mm, P<0.05),
      LVESD((3.07+/-0.39) mm vs. (3.46+/-0.52)mm, P<0.05), the heart weight/body weight
      ratio((0.59+/-0.06)% vs. (0.68+/-0.10)%, P<0.05)was significantly lower and
      infarct size ((23.4+/-2.36)% vs. (39.4+/-2.06)%, P<0.05) was significantly
      reduced in MI+ Sch B group than those in MI+ vehicle group. In MI+ vehicle group,
      HE staining showed a large number of inflammatory cells in the peri-infarctl
      region, and the permutation structure was very disorganized, while above changes
      were significantly reduced in the MI+ Sch B group. Masson staining results showed
      that the degree of myocardial fibrosis in MI+ Sch B group was significantly less
      than that of MI+ vehicle group.Moreover, Sch B could down-regulate some
      inflammatory cytokines, like NF-kappaB,TGF-beta,TNF-alpha and IL-1beta, activate
      Akt-eNOS pathway, upgrade Bcl-2 and downgrade Bax and reduce cell apoptosis as
      compared with MI+ vehicle group (all P<0.05). Conclusions: Our results
      demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and attenuate
      cardiac remodeling and improve cardiac function in this mice MI model.Sch B might
      serve as a potential novel therapeutic agent for ischemic heart disease.

PMID- 29166725
TI  - [Effect and related mechanism of miRNA-21 on hydrogen peroxide-induced C-kit(+)
      cardiac stem cells apoptosis].
AB  - Objective: To explored the effect and related mechanism of miRNA-21 on hydrogen
      peroxide-induced C-kit(+) cardiac stem cells apoptosis. Methods: C-kit(+) cardiac
      stem cells were isolated from SD rats by the methods of enzyme digestion and
      magnetic bead. Cells were divided into the following experimental groups: (1)
      negative control mimics (NCM)group: cells were transfected with negative control
      miRNA-21 mimics for 48 hours; (2)mimics group: cells were transfected with miRNA
      21 mimics for 48 hours; (3) NCM+ H(2)O(2) group: negative control miRNA-21 mimics
      were transfected into cells for 48 hours and then treated with 100 MUmol H(2)O(2)
      for 2 hours; (4)mimics+ H(2)O(2) group: miRNA-21 mimics were transfected into
      cells for 48 hours and then treated with 100 MUmol H(2)O(2) for 2 hours. mRNA of
      miRNA-21 was detected by RT-PCR. The apoptosis rate of C-kit(+) cardiac stem
      cells was determined using the annexin V-FITC/PI staining assay. Western blot was
      employed to measure the expression of apoptosis related proteins(Caspase-3, Bax,
      and Bcl-2). Results: (1) Compared with the NCM group, the mRNA expression level
      of miRNA-21 was significantly up-regulated in mimics group, while obviously down
      regulated in NCM+ H(2)O(2) group(all P<0.05). Compared with the mimics group, the
      mRNA expression levels of miRNA-21 in mimics+ H(2)O(2) group was significantly
      downregulated (P<0.05), but remarkably upregulated compared with the NCM+
      H(2)O(2) group(P<0.05). (2) Flow cytometry results indicated that the early
      apoptosis rates were similar between the NCM group and mimics group ((4.57+/
      3.45)% vs. (5.13+/-3.21)%, P>0.05). Compared with the NCM group, the early
      apoptosis rates were remarkably increased ((79.07+/-5.75)% vs.(4.57+/-3.45)%,
      P<0.05) in NCM+ H(2)O(2) group. Compared with the mimics group, the early
      apoptosis was significantly up-regulated in the mimics+ H(2)O(2) group ((30.27+/
      1.36)% vs.(5.13+/-3.21)%, P<0.05), which were further down-regulated in mimics+
      H(2)O(2) group compared with the NCM+ H(2)O(2) group ((30.27+/-1.36)% vs.(79.07+/
      5.75)%, P<0.05). (3) Western blot results showed similar protein expression of
      Caspase-3, Bax and Bcl-2 between NCM group and mimics group(all P>0.05). Compared
      with the NCM group, the Caspase-3 and Bax protein expression was significantly
      increased in NCM+ H(2)O(2) group (all P<0.05), but the protein expression level
      of Bcl-2 was similar between the 2 groups(P>0.05). The Caspase-3 and Bax protein
      expression was markedly decreased, while Bcl-2 apparently increased in the
      mimics+ H(2)O(2) group compared with the NCM+ H(2)O(2) group(all P<0.05).
      Conclusion: Overexpression of miRNA-21 protects the C-kit(+) cardiac stem cells
      from apoptosis caused by oxidative stress through downregulating proapoptotic and
      upregulating the antiapoptotic proteins.

PMID- 29166726
TI  - [Interaction between TRPC1 and STIM1 in calcium sensing receptor mediated calcium
      influx and nitric oxide production in human umbilical vein endothelial cells].
AB  - Objective: To investigate the interaction of Ca(2+) protein TRPC1 and STIM1 in
      extracellular Ca(2+) -sensing receptor (CaR)-induced extracellular Ca(2+) influx
      and the production of nitric oxide (NO). Methods: Human umbilical vein
      endothelial cells (HUVECs) were cultured and incubated with CaR agonist spermine
      (activating store-operates cation channels (SOC) and receptor-operated channels
      (ROC)), CaR negative allosteric modulator Calhex231 (blocking SOC, activating
      ROC) and ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC)
      inhibitor Ro31-8220, PKCs and PKCMU inhibitor Go6967(activate SOC, blocking ROC),
      respectively. The interaction of TRPC1 and STIM1 was determined using the
      immunofluorescence methods. The interaction between TRPC1 and STIM1 were examined
      by Co-immuno precipitation. The HUVECs were divided into: TRPC1 and STIM1 short
      hairpin RNA group (shTRPC1+ shSTIM1 group), vehicle-TRPC1+ vehicle-STIM1 group
      and control group. The cells were incubated with four different treatments under
      the action of above mentioned interventions, intracellular Ca(2+) concentration
      ([Ca(2+) ](i)) was detected using the fluorescence Ca(2+) indicator Fura-2/AM,
      the production of NO was determined by DAF-FM. Results: (1) The expression of
      TRPC1 and STIM1 proteins levels in HUVECs: Under the confocal microscope, TRPC1
      and STIM1 protein expression showed masculine gender, both located in cytoplasm
      in the normal control group. Post incubation with Calhex231+ TPA, Ro31-8220 and
      Go6967, TRPC1 and STIM1 positioned in cytoplasm was significantly reduced, and
      the combined TRPC1 and STIM1 was also significantly reduced. (2) The interaction
      of TRPC1 and STIM1 in HUVECs: The relative ratios of Calhex231+ TPA+ Spermine+
      Ca(2+) group, Ro31-8220+ Spermine+ Ca(2+) group and Go6976+ Spermine+ Ca(2+)
      group STIM1/TRPC1 and TRPC1/STIM1 were as follows: (25.98+/-2.17)% and (44.10+/
      4.01)%, (20.85+/-1.01)% and (46.31+/-3.47)%, (23.88+/-2.05)% and (39.65+/-2.91)%,
      which were significantly lower than those in the control group (100.00+/-4.66)%
      and (100.00+/-6.40)% and in the Spermine+ Ca(2+) group (106.04+/-2.45)% and
      (107.78+/-2.66)% (all P<0.05). (3) The influence of joint TRPC1 and STIM1
      transfection to four different drugs treated HUVECs on [Ca(2+) ](i) and NO
      generation: The changes of two excitation fluorescence intensity ratio and NO net
      fluorescence intensity values were consistent, [Ca(2+) ](i) and NO net
      fluorescence intensity values were significantly lower in the experimental group
      than the control group and the vehicle group (all P<0.05), while which were
      similar between the vehicle group and control group (all P>0.05). Conclusions:
      Our results indicate that TRPC1 and STIM1 jointly regulate CaR-mediated Ca(2+)
      influx and nitric oxide generation in HUVECs in the form of binary complex.

PMID- 29166727
TI  - [Analysis on the trends in mortality following acute myocardial infarction from
      1999 to 2015 in Tianjin of China].
AB  - Objective: To explore the trends change in mortality following acute myocardial
      infarction (AMI) from 1999 to 2015 in Tianjin, China. Methods: AMI mortality data
      from 1999 to 2015 were obtained from Tianjin population based mortality
      surveillance system operated by the Tianjin Centers for Disease Control and
      Prevention (CDC), and population data of permanent residents were obtained from
      Tianjin Municipal Public Security Bureau. The trends change and affecting factors
      including gender, age, and geographic distribution on mortality following AMI
      were analyzed. Results: (1)The standardized mortality rate of AMI in Tianjin from
      1999 to 2015 was 52.32/100 000 to 48.62/100 000. Adjusted AMI mortality rate from
      1999 to 2013 was 52.32/100 000 to 73.72/100 000, indicating an increased
      trend(Z=32.15, P<0.001)with an annual percent change (APC) of 2.53%. Adjusted AMI
      mortality rate was decreased from 2013 to 2015: 73.72/100 000 to 48.62/100 000
      (Z=-22.80, P<0.001), and APC was -19.07%. Above trends change was similar for
      male and female residents (all P<0.001). (2)The AMI standardized mortality rate
      of male was significantly higher than that of female during the 17 years. The AMI
      standardized mortality of male was significantly higher than that of female
      in<35, 35-44, 45-54, 55-64 and >=65 years old group, respectively. AMI mortality
      rate increased with age. (3)Except in the year of 2002 and 2003, the AMI
      mortality rate were significantly higher in rural residents than in urban
      residents during this study period (P<0.001). Adjusted AMI mortality in urban
      residents increased from 1999 to 2009(Z=8.05, P<0.001, APC=1.43%), and decreased
      in the year from 2009 to 2015 (Z=-18.71, P<0.001, APC=-6.32%). Adjusted AMI
      mortality in rural residents increased in the year of 1999 to 2013(Z=56.05,
      P<0.001, APC=5.84%), and decreased in the year of 2013 to 2015 (Z=-24.40,
      P<0.001, APC=-21.35%). Conclusions: Our results suggest that AMI mortality in
      Tianjin increased from 1999 to 2013, and decreased from 2013 to 2015, and male
      and rural residents have higher AMI mortality. Related prevention and
      intervention measures should be taken to decrease AMI mortality, especially for
      male and rural residents.

PMID- 29166728
TI  - [Anterior descending branch originated from the right coronary artery with
      myocardial bridging terminating in the interventricular septum detected in a
      patient with intermittent syncope].

PMID- 29166729
TI  - [Use dependence and reverse use dependence of antiarrhythmic drugs].

PMID- 29166731
TI  - [Research progress on the prevention and therapy for chemotherapy-related
      cardiotoxicity and cardiomyopathy].

PMID- 29166730
TI  - [Efficacy and safety of subcutaneous implantable cardioverter defibrillator].

PMID- 29166732
TI  - [Application of pegylated recombinant human granulocyte colony-stimulating factor
      to prevent chemotherapy-induced neutropenia in patients with lymphoma: a
      prospective, multicenter, open-label clinical trial].
AB  - Objective: To evaluate the efficacy and safety of pegylated recombinant human
      granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia
      after chemotherapy in patients with lymphoma. Methods: This was a multicenter,
      single arm, open, phase IV clinical trial. Included 410 patients with lymphoma
      received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as
      prophylactic. The primary endpoint was the incidence of III/IV grade neutropenia
      and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of
      antibiotics application during the whole period of chemotherapy was observed.
      Results: 1Among the 410 patients, 8 cases (1.95%) were contrary to the selected
      criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12
      cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%)
      develpoed disease progression or recurrence, thus the rest 321 cases (78.29%)
      were into the Per Protocol Set. 2During the first to fourth treatment cycles, the
      incidences of grade IV neutropenia after prophylactic use of PEG-rhG-CSF were
      19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) ,
      respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54%
      (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG
      rhG-CSF, the incidences of IV grade neutropenia decreased from 61.54% (40/65) in
      the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3
      cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the
      screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles,
      respectively. 3The proportion of patients who received antibiotic therapy during
      the whole period of chemotherapy was 34.39% (141/410) . 4The incidence of adverse
      events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse
      events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) .
      Conclusion: During the chemotherapy in patients with lymphoma, the prophylactic
      use of PEG-rhG-CSF could effectively reduce the incidences of grade III/IV
      neutropenia and FN, which ensures that patients with lymphoma receive standard
      dose chemotherapy to improve its cure rate.

PMID- 29166733
TI  - [Comparative study on the efficacy and safety between pegfilgrastim (PEG-rhG-CSF)
      and recombinant human granulocyte colony-stimulating factor in promoting
      hematopoietic recovery after allogeneic hematopoietic stem cell transplantation
      after hematological malignancy].
AB  - Objective: To observe the efficacy and safety between Pegfilgrastim (PEG-rhG-CSF)
      and Recombinant human granulocyte colony stimulating factor (rhG-CSF) in
      hematological malignancy after allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) . Methods: 157 patients after allo-HSCT were enrolled in this study
      from June 2015 to November 2016. Two agents of G-CSF were used to stimulate
      hematopoietic recovery after transplantation. There were 65 cases in PEG-rhG-CSF
      and 92 cases in rhG-CSF groups. Patients in PEG-rhG-CSF group were given a single
      subcutaneous dose of 6 mg on the first day and +8 d, while cases in rhG-CSF group
      were given in dose of 5 MUg.kg(-1).d(-1) by subcutaneous injection from +1 d
      continuing to neutrophils more than 1.5*10(9)/L, and then the indicators and
      survival rates in two groups after transplantation were compared. Results: 1There
      were no significant differences of the neutrophil implantation time[13.5 (8-12) d
      vs 13 (9-24) d, P=0.393] and platelet implantation time [14 (9-160) d vs 14 (9
      92) d, P=0.094] between PEG-rhG-CSF and rhG-CSF groups respectively. There were
      no significant differences in terms of neutropenia period (P=0.435) , number of
      cases who got fever during neutropenia (P=0.622) , and the median time of fever
      in neutropenia period (P=0.460) , respectively between the two groups. There were
      no significant differences of erythrocyte and platelet transfusions (P=0.074,
      P=0.059) within 1 month after transplantation. 2There were no significant
      differences with regard to the incidences of acute GVHD[23.1% (15/65) vs 34.8%
      (32/92) , P=0.115], chronic GVHD[20.0% (13/65) vs 32.6% (32/92) , P=0.081], II
      IVdegree of acute GVHD[30.0% (13/65) vs 30.4% (30/92) , P=0.287] and extensive
      chronic GVHD[9.2% (6/65) vs 20.7% (19/92) , P=0.135] between PEG-rhG-CSF and rhG
      CSF groups. 3There were no significant differences in terms of disease free
      survival (DFS) (62.5% vs 61.4%, P=0.478) and overall survival (OS) (67.4% vs
      67.3%, P=0.718) between PEG-rhG-CSF and rhG-CSF groups. 4There was no significant
      difference of the non-relapse mortality (NRM) between PEG-rhG-CSF and rhG-CSF
      groups[20.5% (95%CI 11.4%-37.0%) vs 32.6% (95%CI 22.2%-47.9%) , P=0.141]. The
      relapse rate was not statistically significant[14.9% (95%CI 7.4%-29.8%) vs 10.0%
      (95%CI 5.0%-20.0%) , P=0.299]. Conclusion: Compared with rhG-CSF, PEG-rhG-CSF
      could reduce the times of injection. There were no differences in terms of
      hematopoietic recovery, the incidence of GVHD, relapse rate, DFS and OS rates
      after allo-HSCT between two groups.

PMID- 29166734
TI  - [A retrospective study of the BiRd regimen in the treatment of relapsed/
      refractory multiple myeloma].
AB  - Objective: To evaluate efficacy of the BiRd regimen, a combination of
      clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients
      with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM
      treated with BiRd between September 11, 2013 and August 1, 2016 at six centers
      were included to evaluate overall survival rate (ORR) , clinical benefit rate
      (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as
      adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable,
      and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1
      sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients
      with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of
      which 5 patients with >=MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ]
      together with at least one of other adverse-prognostic cytogenetic (e.g.13q-
      and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR
      were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range
      1.0-33.8) months, the median PFS and OS were 12.0 (95%CI 11.6-12.4) and 27.6
      (95%CI 15.1-40.1) months, respectively. The BiRd regimen was well tolerated.
      Conclusion: The BiRd regimen is an effective and safety protocol for RRMM,
      including those carrying high-risk cytogenetic markers.

PMID- 29166735
TI  - [The specific cytotoxicities of chimeric antigen receptor-engineered T cells on
      different lymphomas].
AB  - Objective: To investigate the specific cytotoxicities of the second and third
      generations of chimeric antigen receptor (CAR) -engineered T cells (CAR-T) on
      different lymphomas. Methods: CAR-Ts were prepared by lentivirus packaging and
      infection of T cells. CCK-8, ELISA and Lactate dehydrogenase cytotoxicity assay
      were applied to detect the proliferation capacity, the secretion level of
      inflammatory factor and the specific cytotoxicity. Flow cytometry assay showed
      the specific cytotoxicity and residual level of CAR-T in lymphomas of treated
      mice. Results: The results showed that the third generation CAR-T had greater
      capacity of the specific cytotoxicity and proliferation capacity than of the
      second generation CAR-T. But there was no prominent change of the secretion level
      of inflammatory factor. The specific cytotoxicity of the second generation CAR-T
      on highly aggressive lymphomas Raji was more prominent than in inert EHEB, but
      also could achieve satisfactory effect. The tumor burden in the mice injected
      with Raji was lower than in the mice injected with EHEB from nude mice
      experiment. But the residual level of CAR-T in the EHEB-injected mice was higher
      than in the Raji-injected ones. So the second generation CAR-T was more suitable
      for the treatment of indolent lymphoma. Conclusion: The second generation CD19
      CAR-T could treat aggressive lymphoma in a relatively short period, while the
      second generation CD19 CAR-T need a longer time in vivo to achieve satisfactory
      curative effect on the noble lymphoma.

PMID- 29166736
TI  - [Prognosis of the central nervous system involvement in patients with
      hemophagocytic lymphohistiocytosis].
AB  - Objective: To investigate the characteristics and prognostic factor of central
      nervous system (CNS) involvement in patients with hemophagocytic
      lymphohistiocytosis (HLH) . Methods: From January 2006 to October 2015, 152
      patients with HLH, 88 patients had CNS involvement, their clinical data were
      collected, and survival was analyzed using the Kaplan-Meier life table method,
      univariate and multivariate Cox regression model analyses were applied to
      identify the risk factors of prognosis. Results: 157.9% patients complicated with
      neurological symptoms, cerebrospinal fluid abnormalities were observed in 37.0%
      patients, 57.5% patients had abnormal neuroradiology. 236 patients survived well,
      3 patients lost to follow-up, 49 dead, 1 survival patient had epilepsy. 3The 3
      year overall survival rate of 88 patients was 44%. 4abnormal CSF and unreceived
      IT bore a significant, independent adverse prognostic value (P<0.05) .
      Conclusion: CNS involvement in HLH has a high frequency and poor prognosis, few
      patients remained neurologic sequelae; abnormal CSF related to poor prognosis,
      positive intrathecal injections could improve the prognosis.

PMID- 29166737
TI  - [Clinical analysis of patients with hemophagocytic lymphohistiocytosis
      complicated with gastrointestinal bleeding].
AB  - Objective: To explore the clinical features of patients with hemophagocytic
      lymphohistiocytosis (HLH) complicated with gastrointestinal bleeding. Methods:
      The clinical data of 52 patients with HLH diagnosed from January 2015 to February
      2017 were analyzed retrospectively. Results: 1Of the 52 patients[including 36
      cases of EBV related (69.2%) , 5 cases of lymphoma related (9.6%) , 3 cases of
      primary HLH (5.8%) , 3 cases of rheumatism related (5.8%) , 2 cases of
      tuberculosis related (3.8%) , 3 cases of unknown causes (3.8%) ], 32 cases were
      male (61.5%) and 20 cases female (38.5%) with a median age of 26 (6-64) years
      old. 2The overall survival rates at 1, 3, 6 and 12 months were 74.7%, 53.8%,
      32.9% and 23.3% respectively. 3Multivariate analysis (logistic regression) showed
      thrombocytopenia (P=0.036) and other sites of hemorrhage (P=0.030) were risk
      factors of poor prognosis, and allogeneic hematopoietic stem cell transplantation
      (allo-HSCT, P=0.026) was the influence of good prognostic factor. Conclusion: HLH
      combined with gastrointestinal bleeding was an entity of disease with poor
      prognosis. Thrombocytopenia and other sites of bleeding had a significant
      negative impact on patients, allo-HSCT produced a significant positive impact on
      patients.

PMID- 29166738
TI  - [Expression characteristics and prognosis significance of miRNA-181a in acute
      myeloid leukemia with normal karyotype].
AB  - Objective: To study the expression of miRNA-181a in acute myeloid leukemia (AML)
      patients with normal karyotype to probe its prognosis significance. Methods: The
      expression level of miRNA-181a in bone marrow mononuclear cells of 120 de novo
      AML patients with normal karyotype was detected by real time fluorescence
      quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2,
      NPM1, FLT3-ITD, DNMT3A and CEBPalpha mutations in CN-AML patients after PCR. The
      relationship between miRNA-181a expression and gene mutation, the clinical
      parameters and prognosis were analyzed. Results: The rates of overall surviva1
      (OS) in high expression and low expression groups were 25.0 months and 15.0
      months, respectively (P<0.05) . Relapse free survival (RFS) in high expression
      and low expression groups were 21.4 months and 11.2 months, respectively (P<0.05)
      . Significantly higher level hemoglobin, complete remission rate and proportion
      of wild type NPM1 expression in the high expression of miRNA-181a group were
      observed when compared with the lower expression of miRNA-181a group (P<0.05) .
      Multivariate Cox regression analysis showed miRNA-181a overexpression was an
      independent prognostic factor for CN-AML (HR=2.219, 95%CI 1.601~2.432, P=0.018) .
      Conclusion: Higher expression of miRNA-181a was a good prognostic factor
      independent of clinical parameters and high frequency gene mutations, which
      implicated that the miRNA-181a expression level could be used as an important
      prognostic indicator of AML patients with normal karyotype.

PMID- 29166739
TI  - [Study of the effects and mechanism of all-trans retinoic acid on leukemic cell
      line U937 cells with NPM1 mutation].
AB  - Objective: To investigate the effect and mechanism of all-trans retinoic acid
      (ATRA) on leukemic cell line U937 cells with NPM1 mutation. Methods: Human acute
      myeloid leukemia cell line U937 was explored, NPM1 mutated (A type) plasmids were
      transfected into U937 to form stable clones A1 and A2, which were identified by
      Western blot and Co-immunoprecipitation. The cell proliferation was measured by
      methylthiazolyl tetrazolium bromide (MTT) ; cell cycle and cell apoptosis were
      explored by flow cytometric; cell colony formation was measured by microscope
      count, the molecular pathways related to cell proliferation were measured by
      Western blot. Results: 1The cell proliferations of mutant A1 and A2 were
      inhibited significantly by 52.6% and 35.8% (P<0.05) , respectively under ATRA
      exposure. 2The percentages of G(0)/G(1) stage of mutant A1 and A2 increased by
      20.1% and 35.8%, respectively under ATRA exposure. 3All the U937 leukemic cells
      were inhibited under ATRA exposure; the decreased percentages of vector, wild
      type and mutant NPM1 cells were 32.7%, 57.9% and 90.9% respectively. 4p-ERK
      decreased obviously after ATRA exposure in NPM1 mutated leukemic cells. 5More
      mutant NPM1 cells inclined to apoptosis under the exposure of ATRA and cytotoxic
      drugs than cytotoxic drugs alone, meanwhile more cells apoptosis occurred when
      ATRA was administrated after cytotoxic drugs exposure. Conclusions: ATRA could
      inhibit cell proliferation and colony formation, blocked the cell cycle in the
      G(0)/G(1) stage accompanied by the significant reduction of p-ERK in U937
      leukemic cells with NPM1 mutation. Besides, ATRA could synergize with drugs to
      suppress the leukemic cells survival more effectively when ATRA was administered
      after the cytotoxic drugs exposure in U937 leukemic cells with NPM1 mutation.

PMID- 29166740
TI  - [Factors associated with early treatment response in adults with acute myeloid
      leukemia].
AB  - Objective: To explore the factors influencing early treatment responses in adult
      with de novo acute myeloid leukemia (AML) . Methods: Data of consecutive newly
      diagnosed AML (non-acute promyelocytic leukemia) adults were analyzed
      retrospectively. To assess the impact of clinical characteristics at diagnosis
      and induction regimen on achieving morphologic leukemia-free state (MLFS) , blood
      counts and minimal residual leukemia (MRD, positive MRD defined as RQ-PCR WT1
      mRNA >=0.6% and/or any level of abnormal blast population detected by flow
      cytometry) at the time of achieving MLFS. Results: 739 patients were included in
      this study. 406 (54.9%) patients were male, with a median age of 42 years (range,
      18-65 years) . In the 721 evaluable patients, MLFS was achieved in 477 (66.2%)
      patients after the first induction regimen and 592 (82.1%) within two cycles. A
      total of 634 patients (87.9%) achieved MLFS, including 534 (84.2%) achieving a
      complete remission (CR, defined as MLFS with ANC >= 1*10(9)/L and PLT >=
      100*10(9)/L) , 100 (15.8%) achieving a CRi (defined as MLFS with incomplete ANC
      or PLT recovery) , respectively. 260 (45.9%) patients of 566 (89.3%) who detected
      MRD at the time of achieving MLFS had positive MRD. Multivariate analyses showed
      that female gender, favorable-risk of SWOG criteria, IA10 and HAA/HAD as
      induction regimen were factors associated with achieving early MLFS. In addition,
      low bone marrow blasts, HGB >= 80 g/L, PLT counts<30*10(9)/L and mutated NPM1
      without FLT3-ITD were factors associated with achieving MLFS after the first
      induction regimen; Negative FLT3-ITD mutation was factor associated with
      achieving MLFS within two cycles. PLT counts >=30*10(9)/L and IA10, IA8 or
      HAA/HAD as induction chemotherapy were factors associated with achieving CR.
      Female gender, favorable-risk of SWOG criteria, FLT3-ITD mutation negative,
      mutated NPM1 without FLT3-ITD were factors associated with negative MRD.
      Conclusions: Female gender, favorable molecular markers or cytogenetics, and
      standard-dose induction regimen were key factors associated with higher
      probability of early and deep responses in adults with AML.

PMID- 29166741
TI  - [The study of expression and prognostic value of CD123 in acute myeloid leukemia
      bone marrow blasts].
AB  - Objective: To study the expression of CD123 in bone marrow (BM) blasts of acute
      myeloid leukemia (AML) patients to explore the relationship between CD123
      expression and therapeutic response and prognosis. Methods: This study
      retrospectively analyzed expression and distribution of CD123 in BM blasts in 137
      cases of newly diagnosed AML (excluded M(3)) , CD123 detected by flow
      cytometry>=20% was defined as positive, including 84 CD123(+) AML and 53 CD123(-)
      AML, efficacy and prognosis were compared between the two groups. Results: 1
      Among 137 patients, 84 were in group CD123(+) (61.3%) , and 53 in group CD123(-)
      (38.7%) . All 137 patients were classified into risk groups based on cytogenetic
      and molecular biology abnormalities. No significant differences were seen between
      the three risk groups with regard to their CD123 levels (chi(2)=0.861, P=0.650) .
      Compared with CD123(-) group, the CD123(+) group had higher WBC[47.7 (1.0-264.0)
      vs 22.4 (0.7-211.0) , z=-2.592, P=0.010]. 2 The rates of first complete remission
      (CR1) and recurrence of CD123(+) group were 54.8% (46/84) and 50.8% (32/63) ,
      respectively; and CD123(-) group were 73.6% (39/53) and 41.7% (20/48) ,
      respectively. There was significant difference of CR1 between the two groups
      (chi(2)=5.121, P=0.027) , whereas no significant difference of the recurrence
      rate (chi(2)=0.911, P=0.340) . 3 The median dutations of OS between CD123(+)
      group and CD123(-) group were 20.0 (95%CI 13.1-26.9) months vs 44.0 (95%CI 23.6
      47.3) months, respectively (chi(2)=5.874, P=0.015) ; The median durations of DFS
      were 7.8 (95%CI 1.4-14.1) months vs 18.6 (95%CI 0-39.7) months, respectively, no
      differences were observed between the two groups (chi(2)=2.939, P=0.086) . 4
      CD123 retained an adverse prognosis value on DFS and OS within the intermediate
      group and patients <= 50 years older. Conclusions: CD123 widely expressed in AML
      patients, which was an independent risk factor for CR1 and OS, which implicating
      its important role in evaluating the induction chemotherapy response and
      prognosis of AML.

PMID- 29166742
TI  - [Allogeneic hematopoietic stem cell transplantation for the treatment of acute
      myeloid leukemia with primary thrombocytosis: three cases report and literatures
      review].
AB  - Objective: To investigate the characteristics of the essential thrombocythemia
      (ET) cases transformed to the acute myeloid leukemia (AML) and the role of
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment
      of this disease. Methods: The clinical and laboratory characteristics of 3 ET
      cases before and after transformation and after allo-HSCT were retrospectively
      analyzed, meanwhile the related literatures were reviewed and discussed. Results:
      Case 1 was a male patient of 44 years old, whose PLT was 500*10(9)/L when firstly
      diagnosed ET. After 3 years the disease progressed into myelodysplastic syndrome
      (MDS) while WT1 expression increased from 77 (first visit) to 13 171 copies/10
      000 ABL copies, at the same time chromosome changed dramatically. During the
      period of decitabine treatment the disease processed into AML. Case 2 was a male
      of 58 years old whose PLT was 2 100*10(9)/L when firstly diagnosed ET. The
      disease progressed to AML after 9 years, whose WT1 expression increased from 130
      (first visit) to 3 222 copies/10 000 ABL copies, and he relapsed shortly after
      intensive chemotherapy. Case 3 was a male of 60 years old whose PLT was
      900*10(9)/L when firstly diagnosed ET. The disease progressed to AML after 5
      years, whose WT1 increased from 56 (first visit) to3 696 copies/10 000 ABL
      copies. Moreover leukemia spread to central nervous system (CNS) during
      chemotherapy. Before allo-HSCT, cases 1 did not achieve remission; case 2
      relapsed after a short time of remission and case 3 transferred to CNS leukemia.
      All of the 3 cases underwent allo-HSCT successfully, and they all achieved
      completely remission, whose chromosome and gene mutation recovered negative. At
      the same time, CNS leukemia of case 3 disappeared. The median WT1 decreased to 50
      copies/10 000 ABL copies. There was no severe complication during the median time
      of 5 months after allo-HSCT. Conclusions: The patients transformed to AML had
      poor prognosis, allo-HSCT was the only method that can cure the disease now.

PMID- 29166743
TI  - [Extranodal marginal zone lymphoma of bronchus-associate lymphoid tissue: a case
      report and literatures review].

PMID- 29166744
TI  - [Cyclic neutropenia: a case report and literatures review].

PMID- 29166745
TI  - [Clinical characteristics analyses of 27 cases of immunoglobin D multiple
      myeloma].

PMID- 29166746
TI  - [Multiple myeloma associated with myeloid tumor: 5 cases report and literatures
      review].

PMID- 29166747
TI  - [Primary intestinal lymphangiectasia associated with follicular lymphoma: one
      case report].

PMID- 29166748
TI  - [Hemophagocytic syndrome occurred during the induction chemotherapy in a patient
      with acute myeloid leukemia: a case report].

PMID- 29166749
TI  - [New progress in clinical significance of ADAMTS13].

PMID- 29166750
TI  - [Management of cytokine release syndrome during chimeric antigen receptor
      modified T cell therapy].

PMID- 29166751
TI  - Is there a glucose metabolic signature of spreading TDP-43 pathology in
      Amyotrophic Lateral Sclerosis?
AB  - BACKGROUND: Recently, four neuropathological stages of amyotrophic lateral
      sclerosis (ALS) with spreading of transactive response DNA-Binding Protein-43
      pathology were described. Although 18F-FDG PET has been useful in diagnosis and
      prognosis of ALS patients, in vivo disease staging using glucose metabolic
      patterns across the different ALS stages have not been attempted so far. In this
      study, we investigated whether the discriminant brain regions of the
      neuropathological stage model can be translated to metabolic patterns for in vivo
      staging of ALS. Furthermore, we examined the correlation of these metabolic
      patterns with disease duration, the Revised ALS Functional Rating Scale (ALSFRS
      R) and the Forced Vital Capacity (FVC). METHODS: 146 ALS patients (age 66.0 +/-
      11.0 y; 86M/60F) were divided into four metabolic stages depending on glucose
      metabolism in discriminant regions of neuropathological stages. 18F-FDG data were
      analysed voxel-based to compare local metabolic patterns between different
      stages. Additionally, correlation analyses were performed between pathologic
      stage and clinical parameters. RESULTS: Relative hypometabolism was present in
      regions known to be affected from the post- mortem pathological spread model, but
      relative hypermetabolism was also observed across the different ALS stages. In
      particular, stage 4 reflected a different frontotemporal pattern discordant with
      mere progression of stage 1-3, which may point to a potential different subgroup
      in ALS. Furthermore, metabolic stage correlated with disease duration (Spearman
      rho = -0.21, p = 0.01) and FVC (Spearman rho = -0.24, p = 0.04). CONCLUSIONS: The
      neuropathological ALS stages correspond to discriminative regional brain glucose
      metabolism patterns correlating with disease duration and forced vital capacity.
      Furthermore, metabolic stage 4 may represents a separate group of ALS progression
      towards frontotemporal dementia.

PMID- 29166752
TI  - Immunotherapy treatment: an issue for metabolic response.
AB  - Since the beginning of second decade of last century, when it was introduced in
      many oncologic scenarios, immunotherapy has become an important tool in the
      management of a growing number of cancers. Immunotherapy for cancer appears to be
      useful, improving not only progression free survival but also overall survival,
      thus achieving the goal that many advanced cancers, previously considered without
      effective treatment options, have now become successfully treatable. However,
      considering the relatively recent introduction of these drugs in clinical
      scenarios and the continuous release of new drugs, there is a lack of large
      validated clinical experiences and many issues are today debated amongst which
      the evaluation of the response to immune-therapy. Engaging the host immune system
      in fighting against cancer is an energy-consuming process, requiring T-cell
      recruiting; this process, named "pseudo-progression," sometimes produces an
      increase of both dimensional and metabolic ratio of the lesions, as well as the
      appearance of "new lesions." This behavior, always considered as undisputed
      progressive disease when traditional chemotherapy is employed, should be
      carefully considered in the field of immunotherapy, where the phenomenon of
      "flare" followed by regression of the disease can occur. In this paper, Authors
      analyzed the best available evidence in this field, reviewed the most important
      issues concerning the development of immunotherapy, and addressed evidence and
      concerns about the evaluation of response when using immunotherapy drugs, in
      terms of both radiological and nuclear medicine criteria.

PMID- 29166753
TI  - Interventional locoregional treatment and metabolic response: advantages of using
      PET/CT in the evaluation of response to treatment.
AB  - INTRODUCTION: Interventional oncology locoregional therapies are validated
      treatment modalities for primary and secondary tumors in liver, lung, kidney and
      bone. At this time, there is no accordance in the choice of imaging modality to
      assess treatment response. Morphological imaging and RECIST 1.1 criteria based on
      size variation are limited by several critical points. On the other hand the role
      of functional imaging, in particular by [18F]-fluorodeoxyglucose ([18F]-FDG)
      positron emission tomography (PET), in both staging and response evaluation of
      locoregional treatments remains unclear because of the heterogeneous nature of
      available data. The aim of this paper was to summarize the available literature
      illustrating the state of art of metabolic evaluation of response after
      locoregional therapies in the three major organs of interest: liver, lung and
      bone. EVIDENCE ACQUISITION: Medline database was searched for relevant original
      paper evaluating the role of [18F]-FDG PET in interventional oncology treatment
      published up to June 2017 excluding case reports. EVIDENCE SYNTHESIS: Finally 41
      studies papers evaluating the role of [18F]-FDG PET in both staging and in
      response evaluation of locoregional treatments focused on liver tumoral lesions
      (N.=29), on lung lesions (N.=10) and on bone lesions (N.=2) were considered for
      this review. CONCLUSIONS: PET/CT appears to perform well in the assessment of
      response to interventional therapies compared to conventional imaging, not only
      in terms of response evaluation but also as a possible prognostic tool.
      Nevertheless further prospective, homogenous studies are required to confirm
      these data, in particular for lung and bone lesions.

PMID- 29166754
TI  - Advances in oncological treatment: limitations of RECIST 1.1 criteria.
AB  - RECIST 1.1 criteria are the standard for the response assessment of most solid
      tumors on computed tomography (CT). Nevertheless, the emergence of new classes of
      treatment in the lasts decades has brought new challenges in the evaluation of
      response. A PubMed online database literature search was performed in order to
      identify papers in English with full text available published up to September
      2017. Some oncologic treatments, such as antiangiogenic agents, immunotherapy and
      local treatments, have proven to be effective despite atypical patterns of
      response. In patients undergoing these treatments, size-based evaluations, such
      as RECIST1.1, show some limitations, since they often underestimate the response.
      Some modified criteria have been proposed to improve the response assessment in
      several specific settings, such in gastrointestinal stromal tumors treated by
      antiangiogenic agents, hepatocellular carcinoma treated by local ablation or
      solid tumors treated by immunotherapy. New techniques of image analysis and
      imaging modalities other than CT, such as magnetic resonance imaging and positron
      emission tomography, may provide additional information and amend some of the
      limitations of size-based criteria. The emergence of new treatment paradigms and
      the increasing trend toward personalizing treatment should be associated with a
      concomitant evolution of response assessment, in both research and clinical
      settings.

PMID- 29166755
TI  - Hybrid fusion images in diagnostic and therapeutic procedures.

PMID- 29166756
TI  - Use of imaging techniques in large vessel vasculitis and related conditions.
AB  - Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel
      vasculitis (LVV) primarily affecting the aorta and its major branches, mainly
      differentiated by the onset age (>50 years GCA and <40 years TA). In addition,
      temporal artery involvement and polymyalgia rheumatica are typical features of
      GCA, but not TA. Imaging techniques are required to secure the diagnosis of large
      vessel vasculitides, and to monitor the disease course. Both morphological and
      metabolic imaging are involved. Morphological imaging is represented mainly by
      computerized tomography (CT), CT angiography, magnetic resonance (MR), MR
      angiography, color-Doppler sonography (CDS) and high-resolution CDS. Metabolic
      aspects of inflammatory process in LVV can be well studied by positron emission
      tomography/computed tomography with [18F]deoxyglucose ([18F]FDG PET/CT). It has
      an important increasing role in diagnosis, extent assessment and disease activity
      and therapy response evaluation. In the near future the concomitant development
      of increasingly powerful PET/CT scanners, of new radiopharmaceuticals more
      specific for inflammation, and of new PET/MRI hybrid scanners probably will lead
      to a further new step forward in the diagnosis and clinical management of LVV.

PMID- 29166757
TI  - Hybrid imaging of musculoskeletal infections.
AB  - This review article highlights the role of radiological and nuclear medicine
      techniques in diagnosis of musculoskeletal infections with particular regard to
      hybrid imaging of osteomyelitis, prosthetic joint infections, sternal infections
      and spine infections. Authors conclude on the complementary role of the several
      techniques with indications for an appropriate diagnostic flow chart, in the
      light of the recent European Association of Nuclear Medicine guidelines on
      infection.

PMID- 29166758
TI  - Clinical significance of anti-dense fine speckled 70 antibody in patients with
      fibromyalgia.
AB  - Background/Aims: Fibromyalgia (FM) is a common rheumatologic disease
      characterized by chronic widespread pain, along with various clinical
      manifestations including atypical autoimmune characteristics. Despite its high
      prevalence, there remain no approved laboratory tests to identify specific
      manifestations of FM, or to rule out FM from other rheumatic diseases. Anti-dense
      fine speckled 70 (anti-DFS70) antibodies were initially identified as a form of
      anti-nuclear antibodies in a patient with interstitial cystitis. Anti-DFS70
      antibodies are found in <= 10% of healthy individuals, but have suggestive
      negative association with autoimmune diseases; however, the clinical significance
      of these autoantibodies in FM patients remains poorly understood. Methods: We
      examined 39 patients with FM, along with 17 patients with systemic lupus
      erythematosus (SLE), and 19 healthy individuals (HI). Patients were compared
      based on physical measurements, disease duration, tender point counts, FM Impact
      Questionnaire (FIQ) scores, visual analog scale (VAS) for pain, somatic symptoms,
      and anti-DFS70 antibodies. Results: Levels of anti-DFS70 antibodies were
      significantly higher in the FM and HI groups than in those with SLE. Both anti
      DFS70 antibodies and VAS scores were positively correlated with FM. Within the FM
      group, patients with arthralgia had higher anti-DFS70 antibody values compared to
      those without arthralgia (p = 0.024); antibody levels were also higher in
      patients with sleep disturbances relative to those without sleep issues (p =
      0.024). In contrast, there were no correlations between anti-DFS70 antibodies and
      age, body mass index, disease duration, tender point counts, FIQ, short-form
      health survey results, or other clinical manifestations. Conclusions: Anti-DFS70
      antibodies may represent a useful biomarker for differentiating between FM and
      other autoimmune diseases. The levels of anti-DFS70 antibodies were also
      significantly higher among patients with arthralgia and sleep disturbances.
      Further investigations are necessary to evaluate the relationships between anti
      DFS70 antibodies and other cytokines as a predictive marker for pain.

PMID- 29166759
TI  - Magnetic resonance imaging-assessed synovial and bone changes in hand and wrist
      joints of rheumatoid arthritis patients.
AB  - Background/Aims: Magnetic resonance imaging (MRI) is a sensitive and useful
      method for the detection of synovitis and joint destruction in rheumatoid
      arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone
      marrow edema (BME), synovitis, and tenosynovitis have received insufficient
      attention. Therefore, this study evaluated the patterns of bone erosion, BME,
      synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of
      patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI.
      Methods: MRI datasets from 43 RA patients were analyzed. All patients had
      undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken,
      and three had also received MRI of the contralateral wrist and MCP joints. The MR
      images were evaluated for bone erosion, BME, and synovitis in consensus by two
      blinded readers according to the Outcome Measures in Rheumatology Clinical Trials
      (OMERACT) RAMRIS. The MRI-detected tenosynovitis was evaluated based on
      Haavardsholm's tenosynovitis score. Results: The capitate, lunate, triquetrum,
      and hamate bones were the most common sites of erosion and BME and showed the
      highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was
      present in 78.3% of all patients with RA, and the extensor compartment 4 and
      flexor digitorum profundus and superficialis were frequently affected.
      Conclusions: This study identified the distribution and prevalence of MRI
      detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP
      joints in RA patients. The patterns of the MRI-detected abnormalities may help to
      select sites for the application of MRI protocols in clinical trials and
      practice.

PMID- 29166760
TI  - Clinical characteristics and treatment propensity in elderly patients aged over
      80 years with colorectal cancer.
AB  - BACKGROUND/AIMS: Elderly patients (>= 80 years) with colorectal cancer (CRC) tend
      to avoid active treatment at the time of diagnosis despite of recent advances in
      treatment. The aim of this study was to determine treatment propensity of elderly
      patients aged >= 80 years with CRC in clinical practice and the impact of
      anticancer treatment on overall survival (OS). METHODS: Medical charts of 152
      elderly patients (aged >= 80 years) diagnosed with CRC between 1998 and 2012 were
      retrospectively reviewed. Patients' clinical characteristics, treatment
      modalities received, and clinical outcome were analyzed. RESULTS: Their median
      age was 82 years (range, 80 to 98). Of 152 patients, 148 were assessable for the
      extent of the disease. Eighty-two of 98 patients with localized disease and 28 of
      50 patients with metastatic disease had received surgery or chemotherapy or both.
      Surgery was performed in 79 of 98 patients with localized disease and 15 of 50
      patients with metastatic disease. Chemotherapy was administered in only 24 of 50
      patients with metastatic disease. Patients who received anticancer treatment
      according to disease extent showed significantly longer OS compared to untreated
      patients (localized disease, 76.2 months vs. 15.4 months, p = 0.000; metastatic
      disease, 9.9 months vs. 2.6 months, p = 0.001). Along with anticancer treatment,
      favorable performance status (PS) was associated with longer OS in multivariate
      analysis of clinical outcome. CONCLUSION: Elderly patients aged >= 80 years with
      CRC tended to receive less treatment for metastatic disease. Nevertheless,
      anticancer treatment in patients with favorable PS was effective in prolonging OS
      regardless of disease extent.

PMID- 29166761
TI  - Full-blown hyperparathyroidism.

PMID- 29166762
TI  - A portable high-intensity focused ultrasound system for the pancreas with 3D
      electronic steering: a preclinical study in a swine model.
AB  - PURPOSE: The aim of this animal study was to evaluate the safety and feasibility
      of a portable, ultrasonography-guided, high-intensity focused ultrasound (USg
      HIFU) system to treat the pancreas. METHODS: Eight swine were included. Using a
      portable HIFU device (ALPIUS 900, Alpinion Medical Systems), ablations were
      performed on the pancreas in vivo. Different acoustic intensities were applied
      (1.7 kW/cm2 or 1.5 kW/cm2 , n=2 [group A for a pilot study]; 1.5 kW/ cm2 , n=3
      [group B]; and 1.2 kW/cm2 , n=3 [group C]). Magnetic resonance imaging (MRI) was
      performed immediately (group A) or 7 days (groups B and C) after HIFU treatment.
      In groups B and C, serum amylase and lipase levels were measured on days 0 and 7,
      and performance status was observed every day. Necropsy was performed on days 0
      (group A) or 7 (groups B and C) to assess the presence of unintended injuries and
      to obtain pancreatic and peripancreatic tissue for histological analysis.
      RESULTS: Ablation was noted in the pancreas in all swine on MRI, and all
      pathologic specimens showed coagulation necrosis in the treated area. The mean
      ablation areas on MRI were 85.3+/-38.1 mm2, 90.7+/-21.2 mm2, and 54.4+/-30.6 mm2
      in groups A, B, and C, respectively (P>0.05). No animals showed evidence of
      complications, except for one case of a pseudocyst in group B. CONCLUSION: This
      study showed that pancreas ablation using a portable USg-HIFU system may be safe
      and feasible, and that coagulation necrosis of the pancreas was successfully
      achieved with a range of acoustic intensities.

PMID- 29166763
TI  - An Extremely Rare Case of Back and Hip Pain due to the Metastasis of Late
      Recurrent Myxopapillary Ependymoma to the Inguinal Lymph Node.

PMID- 29166764
TI  - Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report.
AB  - Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine carcinoma of the
      skin that shows locoregional or distant metastasis. Metastasis of MCC to body
      cavity effusion is extremely rare; only three cases have been reported so far.
      Metastatic MCC in effusion cytology shows small blue round cells with fine
      stippled chromatin like other small blue round cell tumors such as small cell
      lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients
      good chances at recently advanced therapeutic options. Here, we present a case of
      metastatic MCC to pleural effusion with characteristic single file-like pattern.

PMID- 29166765
TI  - Metal-free, Regio-, and Stereo-Controlled Hydrochlorination and Hydrobromination
      of Ynones and Ynamides.
AB  - We developed an atom-economical and metal-free method for the regio- and stereo
      selective hydrohalogenation of ynones and ynamides using easy to handle DMPU/HX
      (X = Br or Cl) reagents. The reaction operates under mild conditions and a range
      of functional groups is well tolerated. We propose that the hydrohalogenation of
      ynones gives the anti-addition products via a concerted multimolecular AdE3
      mechanism and that the hydrohalogenation of ynamides produces the syn-addition
      products via a cationic keteniminium intermediate.

PMID- 29166766
TI  - Highly Active Graphene Oxide-Supported Cobalt Single-Ion Catalyst for
      Chemiluminescence Reaction.
AB  - Graphene- or graphene oxide (GO)-supported metallic nanoparticles and single
      metal atom as potentially effective catalysts for chemical reactions have
      recently received extensive research interests. However, metal utilization in
      nanoparticle catalysts is limited and metal atoms readily drift on the graphene
      surface and consequently form aggregated large particles, making practical
      applications limited. Here, we report metal ions directly immobilized on GO as a
      novel GO-supported single-ion catalyst for chemiluminecence (CL) reactions. It is
      found that GO-supported cobalt ions with good stability could catalyze strongly
      luminol-H2O2 and lucigenin-H2O2 CL reactions, accompanied by dramatically
      enhanced CL emission. Theoretical studies reveal that the coupling between Co2+
      and GO induces effective polarization charges, improving chemical activity of the
      reaction site, which promotes the generation of intermediate radicals and
      accelerates the CL reactions. This work may be generalized to other GO-supported
      metal ions as catalysts for a wide range of chemical reactions. The developed GO
      supported cobalt single-ion nanocomposites as nanointerfaces may find future
      applications in CL bioassays.

PMID- 29166767
TI  - Effectiveness of Oral Rinsing Solutions on Mucus, Odor, and Plaque in the
      Hospitalized Elderly in Taiwan.
AB  - This quasi-experimental and pretest-posttest study was conducted in Taiwan. The
      effectiveness of three types of oral rinsing solutions (normal saline, 0.2%
      chlorhexidine [CHX], and boiled water) was compared among 120 elderly patients
      (40 patients per group). Data on oral mucus, odor, and plaque were collected at
      admission on Day 1 (Time [T] 0), Day 4 (T1), Day 7 (T2), and Day 10 (T3). The
      results showed that the oral health condition in terms of mucus, plaque, and odor
      improved significantly over time. The effect for the oral condition did not
      differ significantly among the three groups, except for oral odor. At T2, the CHX
      group experienced higher oral odor than did the boiled water group (Solutions *
      Time interaction, F = 3.967, p = .002). Boiled water appears to be a safe and
      effective oral rinsing solution for hospitalized elderly patients.

PMID- 29166768
TI  - Active parents, active children: The importance of parental organized physical
      activity in children's extracurricular sport participation.
AB  - This study investigated whether parental participation in organized and
      unorganized physical activity (PA) was associated with children's participation
      in extracurricular sport. The sample comprised 834 parents and their children
      (aged 6-10 years), living in central Portugal. Questionnaires assessed parental
      PA (organized and unorganized) and extracurricular sport participation in
      children (number of sports and frequency of participation). Multinomial logistic
      regression was applied to assess associations between parental and child physical
      behaviors. Having both parents active was significantly associated with frequent
      participation in more sports both in girls and boys but a strong relation
      according to gender was found. The odds of boys practicing more than one sport
      and more times per week were higher if they had an active father. Girls with
      physically active mothers, particularly with mothers practicing organized PA in a
      regular way, were engaged in more sports and practiced sport more times per week.
      The type of PA practiced by the parents was not related to boys' participation in
      sport. Future interventions should be family-based and focus on the promotion of
      higher levels of parental PA, including organized, in order to improve their
      children's active behaviors.

PMID- 29166769
TI  - Economic evaluation of a nurse-led home and clinic-based secondary prevention
      programme to prevent progressive cardiac dysfunction in high-risk individuals:
      The Nurse-led Intervention for Less Chronic Heart Failure (NIL-CHF) randomized
      controlled study.
AB  - OBJECTIVE: The objective of this study was to assess the cost-effectiveness of a
      long-term, nurse-led, multidisciplinary programme of home/clinic visits in
      preventing progressive cardiac dysfunction in patients at risk of developing de
      novo chronic heart failure (CHF). METHODS: A trial-based analysis was conducted
      alongside a pragmatic, single-centre, open-label, randomized controlled trial of
      611 patients (mean age: 66 years) with subclinical cardiovascular diseases
      (without CHF) discharged to home from an Australian tertiary referral hospital. A
      nurse-led home and clinic-based programme (NIL-CHF intervention, n = 301) was
      compared with standard care ( n=310) in terms of life-years, quality-adjusted
      life-years (QALYs) and healthcare costs. The uncertainty around the incremental
      cost and QALYs was quantified by bootstrap simulations and displayed on a cost
      effectiveness plane. RESULTS: During a median follow-up of 4.2 years, there were
      no significant between-group differences in life-years (-0.056, p=0.488) and
      QALYs (-0.072, p=0.399), which were lower in the NIL-CHF group. The NIL-CHF group
      had slightly lower all-cause hospitalization costs (AUD$2943 per person;
      p=0.219), cardiovascular-related hospitalization costs (AUD$1142; p=0.592) and a
      more pronounced reduction in emergency/unplanned hospitalization costs (AUD$4194
      per person; p=0.024). When the cost of intervention was added to all-cause,
      cardiovascular and emergency-related readmissions, the reductions in the NIL-CHF
      group were AUD$2742 ( p=0.313), AUD$941 ( p=0.719) and AUD$3993 ( p=0.046),
      respectively. At a willingness-to-pay threshold of AUD$50,000/QALY, the
      probability of the NIL-CHF intervention being better-valued was 19%. CONCLUSIONS:
      Compared with standard care, the NIL-CHF intervention was not a cost-effective
      strategy as life-years and QALYs were slightly lower in the NIL-CHF group.
      However, it was associated with modest reductions in emergency/unplanned
      readmission costs.

PMID- 29166770
TI  - Maltreatment, Coping, and Substance Use in Youth in Foster Care: Examination of
      Moderation Models.
AB  - Child maltreatment is associated with negative outcomes such as substance use
      (SU). This study tested relations among maltreatment history, coping behavior,
      and SU behavior in youth residing in foster care. Participants were 210 youth (
      Mage = 12.71 years; SD = 2.95) in foster care who completed self-report measures
      through an audio computer-assisted self-interview program. Using a structural
      equation modeling framework and latent measurement constructs, positive
      associations were identified between maltreatment at baseline and coping behavior
      outcomes as well as SU behavior outcome approximately 4.5 months later.
      Specifically, greater severity and chronicity of maltreatment was associated with
      greater SU behavior as well as indirect action, prosocial, and asocial coping
      behavior. Maltreatment was not significantly related to direct action coping
      behavior. In moderation tests, only asocial coping provided a significant
      interaction effect for SU behavior outcomes; SU behavior did not moderate
      pathways between maltreatment and coping behavior. For youth in foster care, the
      coping approach may be varied and relate differentially to SU behavior outcomes,
      with asocial approaches to coping acting as a buffer for the maltreatment/SU
      relation. Additionally, SU remains an important target for intervention and
      prevention in youth residing in foster care.

PMID- 29166771
TI  - The effects of yoga on stress and psychological health among employees: an 8- and
      16-week intervention study.
AB  - BACKGROUND: The stresses of modern work life necessitate effective coping
      strategies that are accessible and affordable to the general public. Yoga has
      been found to reduce stress in clinical samples, but studies are needed to
      examine standard gym yoga classes among functional individuals. OBJECTIVES: This
      study investigated the effects of 8- and 16-week gym yoga on stress and
      psychological health. DESIGN AND METHOD: Ninety individuals reporting moderate-to
      high stress were randomly assigned to 16 consecutive weeks of yoga, or to a
      waitlist crossover group who did not practice yoga for 8 weeks then practiced
      yoga for 8 weeks. Stress and psychological health variables were assessed at
      baseline, 8 weeks, and 16 weeks. RESULTS: Significant reductions in stress and
      all psychological health measures were found within the Yoga group over 16 weeks.
      When compared to the control group, yoga practitioners showed significant
      decreases in stress, anxiety, and general psychological health, and significant
      increases in well-being. The group who did not practice yoga showed significant
      decreases in stress, anxiety, depression, and insomnia after they crossed over
      and practiced yoga for 8 weeks. CONCLUSIONS: Gym yoga appears to be effective for
      stress amelioration and promotion of psychological health among workers
      experiencing stress.

PMID- 29166772
TI  - Antimicrobial and antiparasitic activities of three algae from the northwest
      coast of Algeria.
AB  - The objective of this study was to investigate the biological activities of
      Algerian algae, Sargassum vulgare, Cladostephus hirsutus and Rissoella
      verruculosa. Antimicrobial activity of the crude extracts and their fractions was
      assessed using the disc diffusion assay, the minimum inhibitory concentration and
      the minimum bactericidal concentration. Antiparasitic activity was studied in
      vitro against the blood stream forms of Trypanosoma brucei brucei and the
      intraerythrocytic stages of Plasmodium falciparum. Ethyl acetate (EA) fractions
      of the three tested algae showed more potent antimicrobial activity against S.
      aureus (7-14.5 mm) and B. cereus (7-10.75 mm), MIC values ranged from 0.9375 to
      7.5 mg mL-1 and MBC values > 15 mg mL-1. Concerning the antiparasitic activity,
      EA factions of S. vulgare (IC50 = 9.3 MUg mL-1) and R. verruculosa (IC50 = 11.0
      MUg mL-1) were found to be more effective against T. brucei brucei, whereas the
      three EA fractions were little active against P. falciparum.

PMID- 29166773
TI  - A simple polymer electrolyte membrane system for enrichment of low-level tritium
      (3H) in environmental water samples.
AB  - Tritium (3H) is an essential tracer of the Earth's water cycle; yet widespread
      adoption of tritium in hydrologic studies remains a challenge because of
      analytical barriers to quantification and detection of 3H by electrolytic pre
      concentration. Here, we propose a simple tritium electrolytic enrichment system
      based on the use of solid polymer electrolyte membranes (PEMs) that can be used
      to enrich 3H in 250-3000 mL environmental water samples to a 10-mL final volume.
      The IAEA PEM-3H system reported here can produce high enrichment factors (>70
      fold) and, importantly, removes some of the deterrents to conventional 3H
      enrichments methods, including the use of toxic electrolysis and neutralization
      chemicals, spike standards, a complex electrolysis apparatus that requires
      extensive cooling and temperature controls, and improves precision by eliminating
      the need for tracking recovery gravimetrics. Preliminary results with varying
      operating conditions show 3H enrichments to 70-fold and higher are feasible,
      spanning a wide range of tritium activities from 5 to 150 TU with a precision of
      ~4.5 %. Further work is needed to quantify inter-sample memory and to establish
      lower 3H detection limits. The IAEA PEM-3H system is open source, with 3-D CAD
      and design files made freely available for adoption and improvement by others.

PMID- 29166774
TI  - A syringic acid derivative and two iridoid glycosides from the roots of Stachys
      geobombycis and their antioxidant properties.
AB  - A new derivative of syringic acid, stageobester A (1) and two iridoid glycosides
      which including a new one, stageoboside A (2), were isolated from the roots of
      Stachys geobombycis. Their structures were elucidated on the basis of
      spectroscopic methods, including extensive NMR and MS spectra. In addition, all
      the isolates were tested for their antioxidant capacity. Compounds 1 and 2 showed
      moderate antioxidant activities against DPPH radical, with IC50 values of 113.33
      +/- 1.53 and 40.33 +/- 2.08 mg/L, respectively.

PMID- 29166775
TI  - Individualized Levels System and Systematic Stimulus Pairing to Reduce Multiply
      Controlled Aggression of a Child With Autism Spectrum Disorder.
AB  - Research has shown that physical aggression is common in individuals with autism
      spectrum disorder (ASD). Interventions for multiply controlled aggression may be
      complex and difficult to implement with fidelity. As a result, the probability of
      treatment efficacy for this class of behavior may suffer. We designed an
      individualized levels system to reduce the physical aggression of an 11-year-old
      female with ASD. We then employed a systematic stimulus pairing procedure to
      facilitate generalization. Results suggest individualized levels systems can
      suppress multiply controlled aggression and that systematic stimulus pairing is
      an effective way to transfer treatment effects from trained therapists to
      caregivers.

PMID- 29166776
TI  - The polysaccharide extracts from the fungi Coprinus comatus and Coprinellus
      truncorum do exhibit AChE inhibitory activity.
AB  - The polysaccharide (PSH) extracts from the edible mushroom species Coprinus
      comatus and Coprinellus truncorum were screened in liquid for their
      acetylcholinesterase inhibitory (AChE) activity. Both extracts were found to
      display inhibition of the aforementioned enzyme reaching similar IC50 values of
      0.62 +/- 0.07 and 0.61 +/- 0.03 mg/mL, respectively. According to the means of
      FTIR spectroscopy, these PSH extracts mostly contained beta-glucans. However, the
      presence of some proteins and polyphenolics as minor ingredients were also
      detected. Compared with existing literature data for anti-AChE activity of the
      sugar samples, the findings within this study may be treated as a profound
      bioactivity. Consequently, this study puts some light on the possible use of the
      screened macrofungi in the palliative treatment of Alzheimer's disease.

PMID- 29166777
TI  - Short Communication: Tenofovir Disoproxil Fumarate/Emtricitabine Fits for All as
      Appropriate HIV-1 Pre-Exposure Prophylaxis?
AB  - Pre-exposure prophylaxis (PrEP) with TDF/FTC significantly reduces the risk for
      HIV-1 transmission, but, to date, nobody knows if PrEP can still be useful in
      case of viruses harboring resistances to TDF/FTC or if alternative antiretroviral
      drugs might be rather proposed in selected cases. We promote the debate by
      describing a case of an acute infection with multiresistant HIV that occurred in
      a young girl who started a relationship with an HIV-infected partner who had a
      known multiresistant HIV.

PMID- 29166778
TI  - A pilot randomized controlled trial of self-help relaxation to reduce post-stroke
      depression.
AB  - OBJECTIVE: To consider the potential of self-help relaxation training to treat
      depression after stroke. DESIGN: Randomized controlled trial with cross-over at
      three months. SETTING: Community. PARTICIPANTS: In total, 21 people with stroke,
      aged 49-82 years. INTERVENTION: Autogenic relaxation CD. MAIN MEASURE: Hospital
      Anxiety and Depression Scale-Depression (HADS-D) subscale. RESULTS: No difference
      in depression change scores was identified between the treatment and control
      groups; however, on two follow-ups, significant positive differences relative to
      screening were found for the treatment group (at 2 months Z = -2.55, P = .011 and
      12 months Z = -2.44, P = .015). A partial eta2 = .07 was identified. CONCLUSION:
      Self-help relaxation holds promise as a self-help treatment for depression after
      stroke. Findings from this trial, considered with others of relaxation for
      depression, suggest that a study including a total of 80 participants would
      likely be sufficient to establish efficacy of the treatment, relative to
      controls, in those with stroke.

PMID- 29166779
TI  - Perceived Neighborhood Environmental Factors That Maximize the Effectiveness of a
      Multilevel Intervention Promoting Physical Activity Among Latinas.
AB  - PURPOSE: This study tested whether a multilevel physical activity (PA)
      intervention had differential effects on PA according to participants'
      perceptions of their neighborhood environment. DESIGN: Two-group cluster
      randomized controlled trial. SETTING: San Diego, California. SUBJECTS: Analytical
      sample included 319 Latinas (18-65 years) from churches randomized to the
      following conditions: PA (n = 8 churches, n = 157 participants) or attention
      control (n = 8 churches, n = 162 participants). INTERVENTION: Over 12 months, PA
      participants were offered free PA classes (6/wk), while attention control
      participants were offered cancer prevention workshops. MEASURES: Baseline and 12
      month follow-up measures included self-report and accelerometer-based moderate to
      vigorous physical activity (MVPA), sociodemographics, and perceived neighborhood
      environment variables. ANALYSIS: Mixed-effects models examined each PA outcome at
      12-month follow-up, adjusted for church clustering, baseline PA, and
      sociodemographics. We tested interactions between 7 baseline perceived
      environment variables and study condition. RESULTS: Neighborhood esthetics was
      the only significant moderator of intervention effects on accelerometer-based
      MVPA and self-report leisure-time MVPA. Participants in the PA intervention had
      significantly higher PA at follow-up than attention control participants, only
      when participants evaluated their neighborhood esthetics favorably. CONCLUSION:
      Perceived neighborhood esthetics appeared to maximize the effectiveness of a
      multilevel PA intervention among Latinas. For sustainable PA behavior change, the
      environments in which Latinas are encouraged to be active may need to be
      evaluated prior to implementing an intervention to ensure they support active
      lifestyles.

PMID- 29166780
TI  - What Influences Parents' Fear about Children's Independent Mobility? Evidence
      from a State-Wide Survey of Australian Parents.
AB  - PURPOSE: To identify factors associated with generalized and stranger-specific
      parental fear (PF) about children's independent mobility (CIM), a critical aspect
      of physical activity. DESIGN: Cross-sectional survey; random sampling frame,
      minimum quotas of fathers, rural residents. SETTING: State of Victoria,
      Australia. SUBJECTS: Parents of children aged 9 to 15 years (n = 1779), 71%
      response rate. MEASURES: Validated measures of PF and fear of strangers (FoS);
      parent, child, social, and environmental factors. ANALYSIS: Unadjusted and
      adjusted linear regression stratified by child age (9-10; 11-13; 14-15). RESULTS:
      Adjusted models explained a substantial proportion of variance across all age
      groups (PF: 33.6%-36.7%; FoS: 39.1%-44.0%). Perceived disapproval from others was
      consistently associated with both outcomes (PF: beta =.11 to 23, p <= .05; FoS:
      beta =.17-.21, p <= .001) as was parents' perception of children's competence to
      travel safely (PF: beta = -.24 to -.11, p <= .05; FoS: beta = -.16 to -.13, p <=
      .01). Factors associated with FoS included having a female child (beta = -.21 to 
      .13, p <= .001), language other than English (beta = .09 to.11, p <= .01), and
      low levels of parent education (beta = -.14 to -08, p <= .05). CONCLUSION: The
      current study suggests that social norms, child competence, and perceptions about
      the benefits of CIM underpin PF. This evidence informs the development of
      interventions to reduce PF and promote CIM and children's physical activity.

PMID- 29166781
TI  - Being an optimist or a pessimist and its relationship with morning cortisol
      release and past life review in healthy older people.
AB  - OBJECTIVE: Investigate the relationship between optimism and pessimism and the
      cortisol awakening response (CAR) and past life review in healthy older people.
      DESIGN: 76 older volunteers summarised their lives, highlighting the most
      important events, impressions and experiences. Cortisol saliva samples were
      collected on two consecutive weekdays. High and low optimism and pessimism groups
      were computed by mean split. MAIN OUTCOME MEASURES: Percentages of positive (PE)
      and negative events (NE) and positive (PCE) and negative cognitions and emotions
      (NCE) were obtained. Optimism and pessimism were measured with the Life
      Orientation Test Revised. The areas under the curve with respect to the ground
      and with respect to the increase were computed, with the latter understood as the
      CAR. RESULTS: The high pessimism group reported more NE and NCE and less PE and
      PCE (p's < 0.041). No significant differences in CAR were found between high and
      low optimism and pessimism groups after removing suspected non-adherent
      participants (p's > 0.116). Higher CAR was related to lower PCE, but higher NCE
      (both p < 0.008). CONCLUSION: Pessimism seems to increase the focus on negative
      aspects of the past, which may lead to a worse perception of life in ageing,
      whereas optimism contributes to a healthier CAR.

PMID- 29166782
TI  - Screening for the C9ORF72 repeat expansion in a greek frontotemporal dementia
      cohort.
AB  - The C9orf72 repeat expansion is a common genetic cause of frontotemporal dementia
      (FTD) and amyotrophic lateral sclerosis (ALS) in European populations. A previous
      study has reported a high frequency of the expansion in Greek ALS. However, no
      data have been reported on the frequency of the expansion in Greek FTD.
      Currently, we investigated the frequency of the C9orfF72 expansion in a well
      characterized cohort of 64 Greek FTD patients. We detected the C9orf72 repeat
      expansion in 9.3% of cases. Overall, 27.7% of familial and 2.2% of sporadic cases
      were expansion-positive. Five out of 6 cases had a diagnosis of behavioral
      variant FTD. All expansion-positive cases had fairly typical FTD presentations.
      Clinical features included motor neuron disease, Parkinsonism and hallucinations.
      We conclude that the overall frequency of C9orf72-positive cases in Greek FTD is
      high, comparable to Greek ALS, similar to some Western European, but
      significantly higher than some Mediterranean FTD populations.

PMID- 29166783
TI  - Improving Asthma-Related Outcomes Among Children Participating in the Head-Off
      Environmental Asthma in Louisiana (HEAL), Phase II Study.
AB  - PURPOSE: Pediatric asthma disproportionately affects low-income and minority
      children. The HEAL (Head-Off Environmental Asthma in Louisiana), Phase II Project
      was a collaborative effort with a primary focus to improve pediatric asthma
      management in New Orleans, Louisiana. The purpose of this article is to report
      clinical outcomes captured at baseline and 12-month follow-up. METHOD: HEAL (Head
      off Environmental Asthma in Louisiana), Phase II was a pre-post intervention
      study that enrolled children ages 2 to 18 years of age with a diagnosis of asthma
      to receive asthma education within the clinic setting. Enrollees received an
      asthma education intervention, an environmental evaluation, and a 12-month follow
      up session. Endpoints included symptom days, level of asthma control, asthma
      exacerbations, emergency room visits, hospitalizations, and missed school days.
      RESULTS: The majority of participants were aged 5 years and older, male, Black,
      and persistent asthmatics. Emergency room visits decreased from 41% to 20% ( p <
      .001). Improvements in coughing (83% to 62%, p < .001), wheezing (50% to 26%, p <
      .001), and chest tightness (29% to 18%, p < .001) were also seen. CONCLUSION: The
      novel intervention was associated with improved asthma outcomes among pediatric
      patients receiving care at the clinical sites in the Greater New Orleans area.

PMID- 29166784
TI  - Performance of the simplified acute physiology score III in acute organophosphate
      poisoning: A retrospective observational study.
AB  - The performances of acute physiology and chronic health evaluation (APACHE) II
      and simplified acute physiology score (SAPS) II have previously been evaluated in
      acute organophosphate poisoning. We aimed to compare the performance of the SAPS
      III with those of the APACHE II and SAPS II, as well as to identify the best tool
      for predicting case fatality using the standardized mortality ratios (SMRs) in
      acute organophosphate poisoning. A retrospective analysis of organophosphate
      poisoning was conducted. The APACHE II, SAPS II, and SAPS III were calculated
      within 24 h of admission. Discrimination was evaluated by calculating the area
      under the receiver operating characteristic curve (AUROC). The SMRs were
      calculated as 95% confidence intervals (CIs). In total, 100 cases of
      organophosphate poisoning were included. The in-hospital case fatality was 19%.
      The median scores of the APACHE II, SAPS II, and SAPS III were 20.0 (10.0-27.0),
      41.0 (28.0-54.8), and 53.0 (36.3-68.8), respectively. The AUROCs were not
      significantly different among the APACHE II (0.815; 95% CI, 0.712-0.919), SAPS II
      (0.820; 95% CI, 0.719-0.912), and SAPS III (0.850; 95% CI, 0.763-0.936). Based on
      these scores and in-hospital case fatality, the SMRs for the APACHE II, SAPS II,
      and SAPS III were 1.01 (95% CI, 0.50-2.72), 1.01 (95% CI, 0.54 -2.78), and 0.98
      (95% CI, 0.33-1.99), respectively. The SAPS III provided a good discrimination
      and satisfactory calibration in acute organophosphate poisoning. It was therefore
      a useful tool in predicting case fatality in acute organophosphate poisoning,
      similar to the APACHE II and SAPS II.

PMID- 29166785
TI  - Elevated Radiation Exposure Associated With Above Surface Flat Detector Mini C
      Arm Use.
AB  - BACKGROUND: This study aims to test the hypothesis that: (1) radiation exposure
      is increased with the intended use of Flat Surface Image Intensifier (FSII) units
      above the operative surface compared with the traditional below-table
      configuration; (2) this differential increases in a dose-dependent manner; and
      (3) radiation exposure varies with body part and proximity to the radiation
      source. METHODS: A surgeon mannequin was seated at a radiolucent hand table,
      positioned for volar distal radius plating. Thermoluminescent dosimeters measured
      exposure to the eyes, thyroid, chest, hand, and groin, for 1- and 15-minute
      trials from a mini C-arm FSII unit positioned above and below the operating
      surface. Background radiation was measured by control dosimeters placed within
      the operating theater. RESULTS: At 1-minute of exposure, hand and eye dosages
      were significantly greater with the flat detector positioned above the table. At
      15-minutes of exposure, hand radiation dosage exceeded that of all other anatomic
      sites with the FSII in both positions. Hand exposure was increased in a dose
      dependent manner with the flat detector in either position, whereas groin
      exposure saw a dose-dependent only with the flat detector beneath the operating
      table. CONCLUSIONS: These findings suggest that the surgeon's hands and eyes may
      incur greater radiation exposure compared with other body parts, during routine
      mini C-arm FSII utilization in its intended position above the operating table.
      The clinical impact of these findings remains unclear, and future long-term
      radiation safety investigation is warranted. Surgeons should take precautions to
      protect critical body parts, particularly when using FSII technology above the
      operating with prolonged exposure time.

PMID- 29166786
TI  - Understanding concentrated insulins: a systematic review of randomized controlled
      trials.
AB  - OBJECTIVE: To compile, analyze, and summarize the literature on concentrated
      insulins (i.e. concentrations >100 units/mL) from randomized controlled trials
      and derive guidance on appropriate use of these agents. METHODS: Searches were
      conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials,
      Trialtrove (through April 2016) and ClinicalTrials.gov (through April 2017) for
      phase 1-4 clinical studies using concentrated insulins. Selected studies included
      multiple-arm, randomized controlled trials evaluating subcutaneously administered
      concentrated insulins. Trial registration numbers (selected studies) were
      searched in Medline, Embase and Google Scholar (through April 2017). Late-phase
      studies were graded using guidance from the Agency for Healthcare Research and
      Quality. RESULTS: Thirty-eight completed trials (7900 participants) and 34
      qualifying publications were identified. Four marketed concentrated insulins were
      evaluated: two long-acting basal (insulin glargine 300 units/mL and insulin
      degludec 200 units/mL [IDeg200]), one rapid-acting prandial (insulin lispro 200
      units/mL [ILis200]), and one prandial/basal (human regular insulin 500 units/mL).
      Early-phase trials established bioequivalence for IDeg200 and ILis200 with the
      corresponding 100 units/mL formulations. Efficacy studies showed noninferior
      glycemic control between comparators for long-acting basal and prandial/basal
      products with generally low severe hypoglycemia. Six additional concentrated
      insulins with completed early-phase development were also identified. CONCLUSION:
      Concentrated-insulin products demonstrated efficacious and safe outcomes in
      appropriate patients. Clinical findings (HbA1c and hypoglycemia) and methodology
      (initiation and titration), patient factors (insulin experience and dosing
      requirements) and treatment characteristics (bioequivalence, potency and device
      features) are important considerations. This overview of these and other factors
      provides essential information and guidance for using concentrated insulins in
      clinical practice.

PMID- 29166787
TI  - Analysis of Expected Costs of Carpal Tunnel Syndrome Treatment Strategies.
AB  - BACKGROUND: Over 500 000 carpal tunnel releases costing over $2 billion are
      performed each year in the United States. The study's purpose is to perform a
      cost-minimizing analysis to identify the least costly strategy for carpal tunnel
      syndrome treatment utilizing existing success rates based on previously reported
      literature. METHODS: We evaluate the expected cost of various treatment
      strategies based on the likelihood of further treatments: (1) a single steroid
      injection followed by surgical release; (2) up to 2 steroid injections before
      surgical release; (3) 3 steroid injections before surgery, and (4) immediate
      surgical release. To reflect costs, we use our institution's billing charges to
      private payers and reimbursements from Medicare. A range of expected steroid
      injection success rates are employed based on previously published literature.
      RESULTS: Immediate surgical release is the costliest treatment with an expected
      cost of $2149 to $9927 per patient. For immediate surgical release to cost less
      than a single injection attempt, the probability of surgery after injection would
      need to exceed 80% in the Medicare reimbursement model and 87% in the
      institutional billing model. A single steroid injection with subsequent surgery,
      if needed, amounts to a direct cost savings of $359 million annually compared
      with immediate surgical release. Three injections before surgery, with "high"
      expected success rates, represent the cost-minimizing scenario. CONCLUSIONS:
      Although many factors must be considered when deciding upon treatment for carpal
      tunnel syndrome, direct payer cost is an important component, and the initial
      management with steroid injections minimizes these direct payer costs.

PMID- 29166788
TI  - Histopathological indices and inflammatory response in the digestive gland of the
      mussel Mytilus galloprovincialis as biomarker of immunotoxicity to silver
      nanoparticles.
AB  - BACKGROUND: Histopathological assessments approaches in bivalves have become an
      important tool in environmental toxicology. This study seeks to develop a
      quantitative histopathological index (Ih) and inflammation score as biomarkers in
      the aim to assess the health status of nanoparticles exposed mussels. METHODS:
      Digestive gland hematoxylin and eosin (H&E) stained sections from Mytilus
      galloprovincialis were assessed after in vivo exposure (for 3, 6 and 12 h) to
      silver nanoparticles (Ag-NPs < 50 nm and Ag-NPs < 100 nm) prior and after
      manipulating the potential uptake pathways (clathrin- and caveolae-mediated
      endocytosis) using amantadine and nystatin as blockers. Quantitative models
      evaluate the impacts of nanoparticles size, as well as their uptake routes within
      different time of exposure on the inflammation intensity, the digestive tubules
      histomorphometry and the histopathological indices. RESULTS: Silver nanoparticles
      clearly induced histopathological alterations in digestive gland (maximum
      inflammation 2.75 with AgNP < 100 nm [p < 0.05]; significant Ih with AgNP < 50 nm
      and AgNP < 100 nm at different time-points [p < 0.05]). Significant Ih were
      recorded after uptake routes were blockade: AgNP < 50 nm + nystatin and AgNP <
      100 nm + amantadine; [p < 0.05] all time-points. CONCLUSIONS: Histopathological
      assessments showed to be promising tool in nanotoxicity which seems to depend on
      nanoparticles size, exposure time and interestingly to uptake routes. It was not
      clear: is it the length of exposure or the size of particles is more impactful.

PMID- 29166789
TI  - A novel approach to infertility treatment of advance-age patient with prominent
      intramural fibroid.
AB  - We report for the first time on a case of infertile advance-age patient with
      large intramural fibroid, who conceived following a course of Ulipristal. The
      patient underwent two fresh fertility preserving IVF cycles, with
      cryopreservation of 9 day-3 embryos, followed by a 12 weeks course of Ulipristal
      (5 mg per day) and a subsequent frozen-thawed embryo transfer with her own
      previously cryopreserved embryos. We, therefore, believe that Ulipristal is a
      valuable addition to treatment armamentarium of advance-age infertile patient
      with prominent intramural fibroid.

PMID- 29166790
TI  - Towards re-purposing BH3-mimetics in Legionella and viral infections.

PMID- 29166791
TI  - Evaluation of WO2017098421: GSK's benzothiazine compounds as CD73 inhibitor
      filings.
AB  - INTRODUCTION: There are considerable interests in the development of novel small
      molecule CD73 inhibitors for the treatment of cancers, autoimmune diseases,
      precancerous syndromes, and other diseases associated with CD73 activity. Areas
      covered: The application claims novel substituted benzothiadiazine derivatives as
      CD73 inhibitors for the treatment of cancer, precancerous syndromes, AIDS,
      autoimmune diseases, infections, atherosclerosis, and ischemia-reperfusion
      injury. Many of the exemplified compounds have pIC50 values between 5 to 8.4
      against CD73. Expert Opinion: These benzothiadiazine derivatives provide good
      leads for the discovery of potent CD73 inhibitors for the treatment of cancer and
      other diseases mediated by adenosine and its action on adenosine receptors.

PMID- 29166792
TI  - Staff views on supporting evidence based practice for children with ASD.
AB  - PURPOSE: A variety of empirically supported interventions are available for
      children with autism spectrum disorder (ASD), but previous research suggests that
      their selection and use within an evidence-based practice (EBP) framework in
      clinical settings is challenging. To date, research has primarily focused on
      identifying individual, organisational, and contextual barriers to EBP rather
      than identifying collaborative solutions to these barriers through consultation
      with staff. The aim of our study was to explore staff views on supporting EBP in
      their work with children with ASD. MATERIALS AND METHODS: We conducted five focus
      groups involving 29 professional (e.g., speech pathologists, teachers),
      paraprofessional (e.g., childcare workers), and managerial staff to explore their
      views. Audio recordings were transcribed verbatim and analysed using thematic
      analysis. RESULTS: Two central themes, comprising six categories, emerged to
      account for the participants' views. Initiative and Effort accounted for the
      range of creative strategies staff had developed to support their engagement in
      EBP. They also expressed the need for A Better Way involving organisational-wide
      support such as this engagement, including peer-to-peer mentoring. CONCLUSIONS:
      The findings suggest that an organisational-wide model to support engagement in
      EBP, with peer-to-peer mentoring at its foundation, may provide a desirable,
      ecologically valid, and acceptable model. Implications for Rehabilitation
      Clinicians and educators recognise the importance of evidence-based practice.
      Efforts to support evidence-based practice have focused mostly on access to
      research evidence. Clinicians and educators in this study were developing their
      own strategies based on intuition. They identified a need for organisation-wide
      approaches to supporting evidence-based practice. Peer-to-peer mentoring appears
      to be an acceptable and viable strategy.

PMID- 29166793
TI  - The use and discontinuation of hormone replacement therapy in women in South
      China.
AB  - OBJECTIVE: The use of hormone replacement therapy (HRT) started later in China
      than in European countries. The purpose of the present study was to investigate
      HRT patterns and reasons for the initiation and discontinuation of HRT among
      women in South China. METHODS: A telephone survey about menopausal status, the
      use of HRT, reasons for HRT discontinuation and duration of HRT treatment was
      conducted in 2014. RESULTS: A total of 825 telephone surveys were carried out,
      and 217 previous HRT users and 390 current users were recruited for this study.
      Among these 607 subjects, 50.7% of the women sought out HRT for hot flushes,
      41.6% for fatigue and 41.5% for sleeplessness. Approximately one-third (35.9%) of
      the patients abandoned HRT during the following year. The reasons for stopping
      HRT were mainly fear of breast and uterine cancer (28.4%), reduced menopausal
      symptoms (22.9%) and the inconvenience of taking pills or seeing a doctor
      (17.9%). The factors related to HRT discontinuation were the age when HRT was
      initiated (odds ratio 1.59, 95% confidence interval 1.19-2.13) and education
      level (odds ratio 0.78, 95% confidence interval 0.62-0.98). CONCLUSIONS: The
      duration of HRT use in women in south China was short, and a high proportion of
      the women discontinued HRT. Given the high discontinuation rate and the low
      medical compliance, Chinese health-care providers still have much to do to let
      women know about the advantages and disadvantages of HRT and to encourage the use
      of HRT appropriately.

PMID- 29166794
TI  - Evaluation of liposomal behavior in the gastrointestinal tract after oral
      administration using real-time in vivo imaging.
AB  - Liposomes are regarded as promising drug carriers for enhancing the
      pharmacological effects of poorly absorbed drugs, such as peptides, following
      oral administration. Liposomal surface modifications by mucoadhesive polymers
      could improve drug absorption through interactions with the mucus layer. The main
      purpose of this study was to establish a method of monitoring the behavior of
      liposomes within the body after oral administration, particularly in the
      gastrointestinal (GI) tract, using a real-time in vivo imaging system (IVIS) to
      elucidate the behavior of surface-modified liposomes. Indocyanine green (ICG) was
      used as a near-infrared dye to label chitosan (CS) or glycol CS (GCS)-modified
      liposomes, and to observe the dynamic behavior of the liposomes in rats by
      noninvasive IVIS after oral administration. First, we validated IVIS results of
      the rat abdomens by comparing them to quantitative measurements of ICG
      fluorescence intensity in tissue homogenates. Nano-sized small unilamellar
      vesicles were retained longer than micro-sized multilamellar vesicles in the GI
      tract. Furthermore, surface-modified liposomes showed longer-term retention in
      the GI tract than unmodified liposomes in fasted rats. Moreover, surface
      modification by CS or GCS effectively prevented the excretion of liposomes from
      the GI tract and prolonged retention in fed rats.

PMID- 29166795
TI  - Pharmacological interventions for preventing acute mountain sickness: a network
      meta-analysis and trial sequential analysis of randomized clinical trials.
AB  - BACKGROUND: Individuals ascending to high altitude are at a risk of getting acute
      mountain sickness (AMS). The present study is a network meta-analysis comparing
      all the interventions available to prevent AMS. METHODS: Electronic databases
      were searched for randomized clinical trials evaluating the use of drugs to
      prevent AMS. Incidence of AMS was the primary outcome and incidence of severe
      AMS, paraesthesia (as side effect of acetazolamide use), headache and severe
      headache, and oxygen saturation were the secondary outcomes. Odds ratio [95%
      confidence interval] was the effect estimate for categorical outcomes and
      weighted mean difference for oxygen saturation. Random effects model was used to
      derive the direct and mixed treatment comparison pooled estimates. Trial
      sequential analysis and grading of the evidence for key comparisons were carried
      out. RESULTS: A total of 24 studies were included. Acetazolamide at 125, 250 and
      375 mg twice daily, dexamethasone and ibuprofen had statistically significant
      lower incidence of AMS compared to placebo. All the above agents except ibuprofen
      were also observed to significantly reduce the incidence of severe AMS.
      Acetazolamide alone or in combination with Ginkgo biloba were associated with
      lower incidence of headache, but higher risk of paraesthesia. Acetazolamide at
      125 mg and 375 mg twice daily significantly reduce the incidence of severe
      headache as like ibuprofen. Trial sequential analysis indicates that the current
      evidence is adequate for the incidence of AMS only for acetazolamide 125 and 250
      mg twice daily. Similarly, the strength of evidence for acetazolamide 125 and 250
      mg twice daily was moderate while it was either low or very low for all other
      comparisons. CONCLUSIONS: Acetazolamide at 125, 250 and 375 mg twice daily,
      ibuprofen and dexamethasone significantly reduce the incidence of AMS of which
      adequate evidence exists only for acetazolamide 125 and 250 mg twice daily
      therapy. Acetazolamide 125 mg twice daily could be the best in the pool
      considering the presence of enough evidence for preventing AMS and associated
      with lower incidence of paraesthesia. Key messages Acetazolamide 125, 250 and 375
      mg twice daily, dexamethasone and ibuprofen reduce the incidence of AMS in high
      altitudes. Adequate evidence exists supporting the use of acetazolamide 125 mg
      and 250 mg twice daily for preventing AMS of which acetazolamide 125 mg twice
      daily could be the best.

PMID- 29166796
TI  - Structure-activity relationship investigation of benzamide and picolinamide
      derivatives containing dimethylamine side chain as acetylcholinesterase
      inhibitors.
AB  - A series of benzamide and picolinamide derivatives containing dimethylamine side
      chain (4a-4c and 7a-7i) were synthesised and evaluated for acetylcholinesterase
      (AChE) and butyrylcholinesterase (BChE) inhibitory activity in vitro. Structure
      activity relationship investigation revealed that the substituted position of
      dimethylamine side chain markedly influenced the inhibitory activity and
      selectivity against AChE and BChE. In addition, it seemed that the bioactivity of
      picolinamide amide derivatives was stronger than that of benzamide derivatives.
      Among them, compound 7a revealed the most potent AChE inhibitory activity (IC50:
      2.49 +/- 0.19 MUM) and the highest selectivity against AChE over BChE (Ratio:
      99.40). Enzyme kinetic study indicated that compound 7a show a mixed-type
      inhibition against AChE. The molecular docking study revealed that this compound
      can bind with both the catalytic site and the peripheral site of AChE.

PMID- 29166797
TI  - Application of dynamic thermal imaging in a photocarcinogenesis mouse model.
AB  - INTRODUCTION: In clinical practice and experimental settings, cutaneous
      premalignant and malignant lesions are commonly diagnosed by histopathological
      biopsy. However, this technique is invasive and results in functional or cosmetic
      defects. Dynamic thermal imaging is a non-invasive technique that quantifies the
      infra-red (IR) radiation emitted by a subject after the introduction of external
      thermal stimuli (such as heat or cold). METHODS: Forty hairless albino (Crl:SKH1
      hr) mice were randomised to the control group or the experimental group. The
      experimental group was regularly irradiated with artificial ultraviolet. Clinical
      photographs, immunohistochemical staining and dynamic thermal imaging results of
      both groups were obtained. RESULTS: As photocarcinogenesis proceeded, faster
      thermal recovery to basal temperature after heat stimuli was significant on
      dynamic thermal imaging. With histopathological correlations, it was possible to
      differentiate normal, premalignant and malignant cutaneous lesions according to
      thermal imaging results. CD 31 staining analysis showed that increased
      vasculature was the key change responsible for different thermal imaging results
      among photocarcinogenesis steps. CONCLUSIONS: Dynamic thermal imaging is useful
      to differentiate normal, premalignant and malignant cutaneous lesions. Increased
      vasculature is the key change responsible for different thermal imaging results.

PMID- 29166798
TI  - GRK2 as a therapeutic target for heart failure.
AB  - INTRODUCTION: G protein-coupled receptor (GPCR) kinase-2 (GRK2) is a regulator of
      GPCRs, in particular beta-adrenergic receptors (ARs), and as demonstrated by
      decades of investigation, it has a pivotal role in the development and
      progression of cardiovascular disease, like heart failure (HF). Indeed elevated
      levels and activity of this kinase are able to promote the dysfunction of both
      cardiac and adrenal alpha- and beta-ARs and to dysregulate other protective
      signaling pathway, such as sphingosine 1-phospate and insulin. Moreover, recent
      discoveries suggest that GRK2 can signal independently from GPCRs, in a 'non
      canonical' manner, via interaction with non-GPCR molecule or via its
      mitochondrial localization. Areas covered: Based on this premise, GRK2 inhibition
      or its genetic deletion has been tested in several disparate animal models of
      cardiovascular disease, showing to protect the heart from adverse remodeling and
      dysfunction. Expert opinion: HF is one of the leading cause of death worldwide
      with enormous health care costs. For this reason, the identification of new
      therapeutic targets like GRK2 and strategies such as its inhibition represents a
      new hope in the fight against HF development and progression. Herein, we will
      update the readers about the 'state-of-art' of GRK2 inhibition as a potent
      therapeutic strategy in HF.

PMID- 29166799
TI  - Awareness of hormone replacement therapy in medical care personnel in Jiaxing,
      China: a questionnaire survey.
AB  - This study was aimed to investigate the attitudes and knowledge of medical
      personnel on hormone replacement therapy (HRT) in treating perimenopausal
      syndrome. A total of 2580 self-administered questionnaire forms were sent to
      medical care professionals and the responses collected were anonymous. The
      questionnaire included information on levels of awareness, benefits, and
      potential risks of HRT. A total of 2158 questionnaire forms were filled and used
      for statistical analysis; 61.4% of gynecologists believed that it was necessary
      to conduct HRT in suitable patients, 89.1% would like to recommend the therapy to
      patients with perimenopausal syndrome, and 83.2% of the participants were willing
      to take training on HRT. The mean score of awareness of HRT among the respondents
      was 3.14 out of 10. The main reason for them to avoid HRT was fear of cancer
      (43.8%), weight gain (30.4%), addiction (21.9%), and thrombus (3.9%). These
      results indicated that a large proportion of gynecologists are willing to
      recommend HRT to a woman complaining of climacteric disorders. However, awareness
      of HRT among the health workers (including gynecologists) is relatively low. They
      are also worried about the risks. A more concerted effort should be made to
      better disseminate information on HRT.

PMID- 29166800
TI  - Comparison of all-cause costs and healthcare resource use among patients with
      newly-diagnosed non-valvular atrial fibrillation newly treated with oral
      anticoagulants.
AB  - OBJECTIVES: Compare costs and healthcare resource utilization (HCRU) among newly
      diagnosed non-valvular atrial fibrillation (NVAF) patients newly treated with
      dabigatran vs apixaban, rivaroxaban, or warfarin. METHODS: Newly-diagnosed adult
      NVAF patients initiating dabigatran, apixaban, rivaroxaban, or warfarin (index
      event) between October 1, 2010-December 31, 2014 were identified using MarketScan
      claims data, and followed until medication discontinuation, switch, inpatient
      death, enrollment end, or study end (December 31, 2015). Dabigatran patients were
      propensity-score matched 1:1 separately with apixaban, rivaroxaban, and warfarin
      patients. Per-patient-per-month (PPPM) all-cause cost, HCRU, and 30-day re
      admissions were reported. Costs were analyzed using generalized linear models.
      RESULTS: Final cohorts, each matched with dabigatran patients, included 8,857
      apixaban patients, 26,592 rivaroxaban patients, and 33,046 warfarin patients.
      Dabigatran patients had lower adjusted PPPM total healthcare, inpatient, and
      outpatient costs compared to rivaroxaban ($4,093 vs $4,636, $1,476 vs $1,862, and
      $2,016 vs $2,121, respectively, all p <= .001) and warfarin ($4,199 vs $4,872,
      $1,505 vs $1,851, and $2,049 vs $2,514, respectively, all p < .001). Adjusted
      costs were similar for dabigatran and apixaban. Dabigatran patients had
      significantly fewer hospitalizations, outpatient visits, and pharmacy claims than
      rivaroxaban patients (0.06 vs 0.07, 4.84 vs 4.96 and 4.80 vs 4.93, respectively,
      all p < .020) and warfarin patients (0.06 vs 0.07, 4.77 vs 6.88, and 4.76 vs
      5.89, respectively, all p < .001). Dabigatran patients had similar
      hospitalizations to apixaban, but higher outpatient visits (4.70 vs 4.31) and
      pharmacy claims (4.86 vs 4.61), both p < .001. CONCLUSIONS: This real-world study
      found adjusted all-cause costs were lower for dabigatran compared to rivaroxaban
      and warfarin patients and similar to apixaban patients.

PMID- 29166801
TI  - Endometriosis resembling endometrial cancer in a postmenopausal patient.
AB  - Endometriosis occurs in 2-4% of postmenopausal women. There have been a few
      reports of endometriosis in women in whom neither history nor diagnostic imaging
      indicated the presence of this disease, either at reproductive age or after
      menopause. A case is described of an 84-year-old patient with extensive deep
      pelvic endometriosis imitating advanced neoplastic process.

PMID- 29166802
TI  - Diagnostic work up of an adult female patient with systemic AA amyloidosis
      revealing the cause of infantile mental retardation.

PMID- 29166803
TI  - Oxidative stress in cerebral small vessel disease. Role of reactive species.
AB  - Cerebral small vessel disease (CSVD) is a wide term describing the condition
      affecting perforating arterial branches as well as arterioles, venules, and
      capillaries. Cerebral vascular net is one of the main targets of localised
      oxidative stress processes causing damage to vasculature, changes in the blood
      flow and blood-brain barrier and, in consequence, promoting neurodegenerative
      alterations in the brain tissue. Numerous studies report the fact of oxidation to
      proteins, sugars, lipids and nucleic acids, occurring in most neurodegenerative
      diseases mainly in the earliest stages and correlations with the development of
      cognitive and motor disturbances. The dysfunction of endothelium can be caused by
      oxidative stress and inflammatory mechanisms as a result of reactions and
      processes generating extensive reactive oxygen species (ROS) production such as
      high blood pressure, oxidised low density lipoproteins (oxLDL), very low density
      lipoproteins (vLDL), diabetes, homocysteinaemia, smoking, and infections. Several
      animal studies show positive aspects of ROS, especially within cerebral
      vasculature.

PMID- 29166804
TI  - Adolescence and risk of preterm birth in multifetal gestations.
AB  - OBJECTIVE: The objective of this study is to evaluate if adolescence confers
      additional risk for preterm delivery in multifetal gestations. METHODS: This is a
      retrospective review of all twin and triplet deliveries from 8/2008 to 12/2012 at
      two Detroit Hospitals. Outcomes in adolescent mothers aged 19 or younger (n = 59)
      were compared with adult controls aged 20-34 (n = 350). RESULTS: Mean gestational
      age at delivery in adolescents was 31.3 (SD: 5.8) weeks versus 34.2 (SD: 4.3)
      weeks in adults (p < .001). On multivariable analysis, adolescence was associated
      with preterm delivery (adjusted odds ratio [aOR], 2.3; 95% confidence intervals
      [95% CI], 1.1-4.7, p = .02) and early-preterm delivery (aOR, 2.2; 95% CI 1.2-4; p
      = .01). Adjusted rates of preterm and early-preterm delivery were markedly higher
      in adolescents compared with controls. Being an adolescent was also a significant
      risk factor for iatrogenic preterm delivery (aOR, 2.4; 95% CI 1.1-5.5; p = .04).
      CONCLUSIONS: Adolescents pregnant with twins or triplets deliver 3 weeks, on
      average, before adults and are at markedly increased risk of preterm and early
      preterm delivery.

PMID- 29166805
TI  - A case of repeated mixed mood episodes with psychotic symptoms associated with
      the premenstrual period in a patient with polycystic ovarian syndrome.
AB  - Studies have demonstrated that estrogen plays an important role in psychotic and
      mood disorders in women. Estrogens have a protective effect against the
      development of these disorders, while hypoestrogenic states may be a risk factor
      for the development or exacerbation of mental illness. Additionally, women with
      menstrual cycle abnormalities such as those with a history of anovulation may be
      more susceptible to monthly estrogen level fluctuation-related mood and psychotic
      symptoms. We present the case of a young woman with polycystic ovarian syndrome,
      who experienced three episodes of premenstrual mixed mood and psychotic symptoms.

PMID- 29166806
TI  - Regulation of stressed-induced cell death by the Bcl-2 family of apoptotic
      proteins.
AB  - Apoptosis is often deregulated in a number of human diseases. Heat-induced
      apoptosis is a model system for studying the consequences of protein misfolding
      and is mediated by the Bcl-2 family of proteins. This family consists of both pro
      apoptotic and anti-apoptotic members that control mitochondrial integrity. The
      BH3-only pro-apoptotic members are strong inducers of apoptotic cell death.
      Protein damaging stress can activate a process of cellular destruction known as
      apoptosis. The pro-apoptotic BH3-only proteins and transcription factors activate
      this death pathway by inhibiting the anti-apoptotic Bcl-2 family proteins
      eliminating cancer cells in a short period of time.

PMID- 29166807
TI  - Secondary Malignancies of the Bladder: Avoiding the Diagnostic Pitfall.
AB  - Although rare, secondary tumors of the bladder can present a diagnostic dilemma
      to pathologists considering a differential diagnosis of primary bladder cancer.
      We investigated the clinicopathologic and imaging characteristics of metastatic
      tumors to the bladder. We retrospectively reviewed the surgical pathology
      databases from 2 sites from 2013 to 2016, identifying 66 cases of secondary
      bladder tumors. Clinical, pathologic, and imaging findings were reviewed. Mean
      age at diagnosis was 63 years (range = 25-87). Females had a significantly higher
      proportion (44/66, 66.7%) of secondary bladder tumors compared with males (22/66,
      33.3%; P = .007). In total, 56/66 (84.8%) patients had a clinical history of an
      in situ or invasive malignancy in another organ, and 54/66 (81.8%) patients had
      imaging supporting a metastatic tumor. Only 2/66 (3.0%) patients had a prior
      history of urothelial carcinoma. In total, 4/66 (6.1%) cases (all females) were
      originally misdiagnosed as primary bladder malignancies and were corrected after
      clinicoradiologic correlation. Overall, colorectal origin was most common (15/66,
      22.7%), followed by cervical and ovarian primaries (10/66, 15.2% each). Cervical
      and ovarian origins predominated in the female cohort (10/44, 22.7% each),
      followed by endometrial (8/44, 18.2%). Colorectal and prostate primaries were the
      most common among males (10/22, 45.5%, and 7/22, 31.8%, respectively). Secondary
      bladder tumors can mimic urothelial carcinomas. In our cohort, gynecological,
      colorectal, and prostatic origins were most common. Clinical history, imaging,
      and immunohistochemical studies can be useful in avoiding this diagnostic
      pitfall.

PMID- 29166808
TI  - Mechanism of NF-kappaB signaling pathway and autophagy in the regulation of
      osteoblast differentiation.
AB  - OBJECTIVE: The objective of the present work was to investigate a possible
      mechanism of NF-kappaB signaling pathway and autophagy in the regulation of
      osteoblast differentiation, and provide experimental basis for the study of tooth
      eruption disorder. METHODS: Mouse osteoblast-like (MC3T3-E1) cells were
      inoculated with a cell density of 70%. According to the grouping experimental
      design, Western blot and monodansylcadaverine (MDC) detection were conducted
      after dosing for 24 h. The cells were divided into the following five groups:
      blank control group; 6.25 ug/mL SN50 group; 12.5 ug/mL SN50 group; 25 ug/mL SN50
      group and 50 ug/mL SN50 group. RESULTS: Western blot analysis revealed that the
      expression of LC3 protein was present in the blank control group; 6.25 ug/mL SN50
      group; 12.5 ug/mL SN50 group and 50 ug/mL SN50 group, with no significant
      differences among these groups. However, the expression of LC3 protein was
      significantly lower in the 25 ug/mL SN50 group. MDC detection showed that, in the
      blank control group; 6.25 ug/mL SN50 group; 12.5 ug/mL SN50 group and 50 ug/mL
      SN50 group, there was obvious green fluorescence in the cytoplasm of the
      osteoblasts. However, in the 25 ug/mL SN50 group, it was found that there were
      significantly fewer green fluorescent particles. CONCLUSION: The osteoblast
      itself had a strong function of autophagy. The appropriate concentration of SN50
      in blocking the NF-kappaB pathway of the osteoblast was associated with the
      obvious inhibition of autophagy. However, the relationship between NF-kappaB
      signaling pathway and autophagy in the process of tooth eruption requires further
      study.

PMID- 29166809
TI  - The relationship of obesity to the timing of permanent tooth emergence in Czech
      children.
AB  - BACKGROUND: The aim of this study was to investigate the influence of BMI on the
      timing of permanent tooth emergence in Czech children. OBJECTIVES: In this cross
      sectional study, 1370 Czech children were examined. The age, gender, weight,
      height, all emerged permanent teeth (except third molars) of each child were all
      recorded. A tooth is defined as having emerged when at least any part of it has
      penetrated the gingiva. METHODS: A logistic regression model was used to
      calculate the median emergence age per tooth for both genders separately and BMI
      was used as a factor variable to detect statistically significant differences in
      the times of tooth emergence within pairs of BMI groups. The data were
      statistically processed using IBM SPSS Statistics 23 (SPSS Inc., Chicago, IL).
      RESULTS: Statistically significant differences were found for the following
      permanent teeth (using the FDI two-digit system): 13, 14, 15, 16, 17, 41, 44, 45,
      46, 47, 33, 35, 37, 21, 24, 25, 26, 27 for girls and 12, 13, 14, 15, 16, 41, 43,
      44, 45, 22, 25, 32, 34, 35, 36 for boys. These teeth were observed to emerge
      earlier in obese children. A similar correlation (although not statistically
      significant) was observed between the time of emergence of the remaining teeth
      and the BMI of the child. CONCLUSION: The data in this research highlight
      significant differences in emergence times of permanent teeth due to the
      influence of BMI in Czech children. These findings are important for dental
      treatment planning.

PMID- 29166810
TI  - Anesthetic management of amniotic fluid embolism -- a multi-center,
      retrospective, cohort study.
AB  - INTRODUCTION: Amniotic fluid embolism (AFE) is a rare and potentially lethal
      obstetric complication, commonly occurring during labor, delivery, or immediately
      postpartum. There is a paucity of data regarding incidence, risk factors, and
      clinical management. Our primary objective in this study was to evaluate clinical
      presentation of AFE and delineate anesthesia management of these cases. METHODS:
      This 10 years retrospective multi-center cohort study was performed in five
      tertiary university-affiliated medical centers, between the years 2005 and 2015.
      All documented cases of AFE identified according to the ICD guidelines were
      reviewed manually to determine eligibility for AFE according to Clark's criteria.
      All cases confirming Clark's diagnosis were included in the cohort. RESULTS:
      Throughout the study period, 20 cases of AFE were identified, with an incidence
      of 4.1 per 100,000 births. Average age at presentation was 35 +/- 5 years.
      Seventy percent of cases presented during vaginal delivery, 20% occurred
      throughout a cesarean delivery, and 10% occurred during a dilation and evacuation
      procedure. The most common presenting symptom was sudden loss of consciousness in
      12 parturients (66.7%), fetal bradycardia in 11 parturients (55%), and shortness
      of breath in 10 parturients (50%). Perimortem cesarean section was performed in
      55% of cases, although only one case was performed in the delivery suite, while
      all others were performed in the operating room. Echocardiography was performed
      in 60% of the cases and all were pathological. Furthermore, 20% of cases were
      connected to an extracorporeal membrane oxygenation machine. There was a 15%
      mortality rate of 15%. A further 15% suffered major neurological disability, 25%
      suffered minor neurological morbidity, and 45% survived without severe
      complications. CONCLUSION: AFE is associated with significant maternal morbidity.
      This study highlights the importance of providing advanced training for the
      delivery suite staff for cases of maternal cardiovascular collapse secondary to
      AFE and increasing awareness for this rare and devastating obstetric condition.

PMID- 29166811
TI  - Adolescent environmental enrichment prevents behavioral and physiological
      sequelae of adolescent chronic stress in female (but not male) rats.
AB  - The late adolescent period is characterized by marked neurodevelopmental and
      endocrine fluctuations in the transition to early adulthood. Adolescents are
      highly responsive to the external environment, which enhances their ability to
      adapt and recover from challenges when given nurturing influences, but also makes
      them vulnerable to aberrant development when exposed to prolonged adverse
      situations. Female rats are particularly sensitive to the effects of chronic
      stress in adolescence, which manifests as passive coping strategies and blunted
      hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood. We
      sought to intervene by exposing adolescent rats to environmental enrichment (EE)
      immediately prior to and during chronic stress, hypothesizing that EE would
      minimize or prevent the long-term effects of stress that emerge in adult females.
      To test this, we exposed male and female rats to EE on postnatal days (PND) 33-60
      and implemented chronic variable stress (CVS) on PND 40-60. CVS consisted of
      twice-daily unpredictable stressors. Experimental groups included:
      CVS/unenriched, unstressed/EE, CVS/EE and unstressed/unenriched (n = 10 of each
      sex/group). In adulthood, we measured behavior in the open field test and forced
      swim test (FST) and collected blood samples following the FST. We found that
      environmental enrichment given during the adolescent period prevented the chronic
      stress-induced transition to passive coping in the FST and reversed decreases in
      peak adrenocortical responsiveness observed in adult females. Adolescent
      enrichment had little to no effect on males or unstressed females tested in
      adulthood, indicating that beneficial effects are specific to females that were
      exposed to chronic stress.

PMID- 29166812
TI  - Disparities in Insurance Coverage, Health Services Use, and Access Following
      Implementation of the Affordable Care Act: A Comparison of Disabled and
      Nondisabled Working-Age Adults.
AB  - The objective of this study was to assess trends in health insurance coverage,
      health service utilization, and health care access among working-age adults with
      and without disabilities before and after full implementation of the Affordable
      Care Act (ACA), and to identify current disability-based disparities following
      full implementation of the ACA. The ACA was expected to have a disproportionate
      impact on working-age adults with disabilities, because of their high health care
      usage as well as their previously limited insurance options. However, most
      published research on this population does not systematically look at effects
      before and after full implementation of the ACA. As the US Congress considers new
      health policy reforms, current and accurate data on this vulnerable population
      are essential. Weighted estimates, trend analyses and analytic models were
      conducted using the 1998-2016 National Health Interview Surveys (NHIS) and the
      2014 Medical Expenditure Panel Survey. Compared with working-age adults without
      disabilities, those with disabilities are less likely to work, more likely to
      earn below the federal poverty level, and more likely to use public insurance.
      Average health costs for this population are 3 to 7 times higher, and access
      problems are far more common. Repeal of key features of the ACA, like Medicaid
      expansion and marketplace subsidies, would likely diminish health care access for
      working-age adults with disabilities.

PMID- 29166813
TI  - The efficacy of RGD modified liposomes loaded with vinorelbine plus tetrandrine
      in treating resistant brain glioma.
AB  - Brain glioma is one of the most common and devastating intracranial malignancies
      with a high mortality. Chemotherapy for brain glioma is not ideal due to blood
      brain barrier (BBB) and multidrug resistance (MDR). The objectives of the present
      study were to develop a kind of RGD (Arg-Gly-Asp) tripeptide modified vinorelbine
      plus tetrandrine liposomes to achieve BBB transportation, MDR reversion and
      glioma cell targeting simultaneously. The studies were performed on glioma cells,
      resistant glioma cells and glioma-bearing mice. Results showed that the
      constructed liposomes with suitable physicochemical properties could
      significantly enhance the transport across BBB, obviously accumulate in glioma
      cells, and exhibit evident capabilities in diminishing brain glioma in mice.
      Action mechanism studies indicated that the enhanced anticancer efficacy could be
      attribute to the follows: prolonged elimination half-life (7.093 +/- 1.311 h);
      increased AUC0-24 h (28.92 +/- 2.66 mg/L*h); transporting across BBB; enhanced
      cellular uptake; down-regulation on P-gp (0.49 +/- 0.06 fold); inducing apoptosis
      via activating caspase 8, 9, and 3 (2.40 +/- 0.22, 3.57 +/- 0.29, and 4.33 +/-
      0.30 folds, respectively). In conclusion, the RGD modified vinorelbine plus
      tetrandrine liposomes may offer a promising therapeutic strategy for treatment of
      brain glioma.

PMID- 29166815
TI  - Disposition of [14C]hydroquinone in Harlan Sprague-Dawley rats and B6C3F1/N mice:
      species and route comparison.
AB  - 1. Hydroquinone (HQ) is present in some foods and has varied industrial, medical
      and consumer uses. These studies were undertaken to investigate the disposition
      of HQ in rats and mice following gavage, intravenous (IV) and dermal exposure. 2.
      [14 C]HQ administered (0.5, 5 or 50 mg/kg) by gavage or IV routes to male and
      female Harlan Sprague-Dawley (HSD) rats and B6C3F1/N mice was well absorbed and
      rapidly excreted primarily in urine. Radioactivity remaining in tissues at 72 h
      was <1% for both species at all dose levels and routes. No sex, species or route
      related differences in disposition were found. 3. With dermal application of 2,
      10 or 20% [14 C]HQ, mice absorbed higher percentages of the dose than rats (37,
      12, 12% versus 18.6, 4.43 and 1.79%, respectively). The HQ mass absorbed by mice
      increased with dose, while in rats it was more constant over the dose range.
      Absorbed HQ was rapidly excreted in urine of both species and urinary excretion
      indicated continued absorption over the exposure period. No sex differences in
      disposition were found. 4. The oral bioavailability of HQ at 5 mg/kg was low in
      both rats (1.6%) and mice (3.9%) demonstrating significant first pass metabolism.
      Dermal bioavailability in mice was 9.4% following application of 2% formulation.
      5. Urinary metabolites for both species and all routes included the glucuronide
      and sulfate conjugates; no parent was found in urine.

PMID- 29166817
TI  - Ambiguities in the taxonomic assignment and species delineation of botryllid
      ascidians from the Israeli Mediterranean and other coastlines.
AB  - Based on mtCOI sequences comparisons, recent studies reassigned the 'dwarf
      Botrylloides leachii' from the Levant as Botrylloides nigrum. Here we conducted a
      survey of the literature and of deposited mtCOI sequences of botryllid ascidians,
      elucidating ambiguities in their taxonomy. We found that the species, dwarf morph
      of Botrylloides leachii, Botrylloides nigrum, Botryllus aster and Botryllus
      arenaceus are grouped together on a single molecular taxon. Then, results of
      three additional markers (18S, 28S, H3) contradicted literature suggestions,
      revealing minute distances between Botrylloides leachii and the 'dwarf
      Botrylloides leachii'. Moreover, only Botrylloides leachii and the 'dwarf
      Botrylloides leachii' develop giant ampullae as an allorecognition response. Our
      results raise the possibility that inadequate identification, together with
      faults in molecular assignment, including queries regarding the efficacy of the
      mtCOI as the exclusive barcoding tool in botryllid ascidians, is the major
      culprits responsible for the emerged inconsistencies between the mtCOI sequences
      and traditional taxonomy. Thus, we assign the Levantine dwarf form as
      Botrylloides aff. leachii.

PMID- 29166816
TI  - Tobacco exposure-related alterations in DNA methylation and gene expression in
      human monocytes: the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - Alterations in DNA methylation and gene expression in blood leukocytes are
      potential biomarkers of harm and mediators of the deleterious effects of tobacco
      exposure. However, methodological issues, including the use of self-reported
      smoking status and mixed cell types have made previously identified alterations
      in DNA methylation and gene expression difficult to interpret. In this study, we
      examined associations of tobacco exposure with DNA methylation and gene
      expression, utilizing a biomarker of tobacco exposure (urine cotinine) and CD14+
      purified monocyte samples from 934 participants of the community-based Multi
      Ethnic Study of Atherosclerosis (MESA). Urine cotinine levels were measured using
      an immunoassay. DNA methylation and gene expression were measured with
      microarrays. Multivariate linear regression was used to test for associations
      adjusting for age, sex, race/ethnicity, education, and study site. Urine cotinine
      levels were associated with methylation of 176 CpGs [false discovery rate
      (FDR)<0.01]. Four CpGs not previously identified by studies of non-purified blood
      samples nominally replicated (P value<0.05) with plasma cotinine-associated
      methylation in 128 independent monocyte samples. Urine cotinine levels associated
      with expression of 12 genes (FDR<0.01), including increased expression of P2RY6
      (Beta +/- standard error = 0.078 +/- 0.008, P = 1.99 * 10-22), a gene previously
      identified to be involved in the release of pro-inflammatory cytokines. No
      cotinine-associated (FDR<0.01) methylation profiles significantly (FDR<0.01)
      correlated with cotinine-associated (FDR<0.01) gene expression profiles. In
      conclusion, our findings i) identify potential monocyte-specific smoking
      associated methylation patterns and ii) suggest that alterations in methylation
      may not be a main mechanism regulating gene expression in monocytes in response
      to cigarette smoking.

PMID- 29166818
TI  - Can Digital Technology Enhance Social Connectedness Among Older Adults? A
      Feasibility Study.
AB  - This study examined the feasibility of a novel communication technology to
      enhance social connectedness among older adults in residential care. Research
      suggests that technology can create opportunities for social connectedness,
      helping alleviate social isolation and loneliness. Studies on implementation and
      feasibility of such technological interventions, particularly among frail and
      institutionalized older adults, are scant. Data were gathered in a 3-month
      deployment with 12 older adults, including semistructured interviews with
      participants and relatives/friends, psychometric scales, field observations, and
      usability tests. Data were analyzed with qualitative profiling, thematic
      analysis, and Friedman tests. The technology was a feasible communication tool,
      although requiring an adaptation period. Use increased perceived social
      interaction with ties, but increased social connectedness (meaningful social
      interaction) was only reported by participants with geographically distant
      relatives. Sense of well-being and confidence with technology was enhanced, but
      negative effects were also observed. Findings are useful for researchers and
      practitioners interested in technological interventions.

PMID- 29166819
TI  - Pregnancy outcomes among women with asthma.
AB  - PURPOSE: The purpose of this study is to examine the association between maternal
      asthma and pregnancy, delivery and neonatal outcomes. MATERIALS AND METHODS: We
      carried out a retrospective cohort study using the Health Care Cost and
      Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database from 2003 to
      2011. Among women who delivered during this time period, we compared pregnancy,
      delivery, and neonatal outcomes in asthmatics versus non-asthmatics. Multivariate
      logistic regression was used to estimate adjusted odds ratios and 95% confidence
      intervals. RESULTS: In a cohort of 7,772,999 pregnant women, 223,236 (2.9%) had
      asthma. The prevalence of asthma-complicated pregnancies rose over the study
      period from 1.9% in 2003 to 3.7% in 2011 (p < .001). Pregnant asthmatics had more
      pre-existing health conditions, such as diabetes, chronic hypertension, obesity,
      and thyroid disease, and were more likely to smoke. Even after adjustment for
      these comorbidities, and other covariates, within statistical models, asthma was
      found to be associated with greater risk of several pregnancy complications:
      gestational hypertension, preeclampsia, gestational diabetes, placenta previa,
      preterm premature rupture of membranes, placental abruption, chorioamnionitis,
      preterm delivery, postpartum hemorrhage, venous thromboembolism, caesarean
      section delivery, and maternal mortality. Neonates born to asthmatics had greater
      risk of being small for gestational age and for having congenital anomalies, and
      lower risk of intrauterine fetal death. CONCLUSIONS: Asthma is associated with an
      increase in adverse pregnancy, labor, and neonatal outcomes. Close surveillance
      of asthmatic patients during the prenatal period is warranted and care in a
      tertiary hospital is advised.

PMID- 29166820
TI  - Sinonasal SMARCB1 (INI1) Deficient Carcinoma With Yolk Sac Tumor Differentiation:
      Report of a Case and Comparison With INI1 Expression in Gonadal Germ Cell Tumors.
AB  - SMARCB1 (INI1) deficient sinonasal carcinoma is a recently recognized entity with
      wide histomorphologic spectrum. We present a case of this carcinoma that
      contained, in addition to a "common" morphology, scattered foci of yolk sac tumor
      differentiation. The tumor occurred in paranasal sinuses in a 44-year-old woman.
      Immunohistochemically, it was diffusely negative for INI1, whereas an expression
      of yolk sac tumor markers (alpha-fetoprotein, glypican-3, CDX2) was limited to
      the yolk sac tumor component. For comparison with the present case, we performed
      INI1 immunostaining on a series of 11 gonadal germ cell tumors with yolk sac
      tumor differentiation. All of these cases showed strong and diffuse expression of
      INI1, in contrast with the present sinonasal tumor. Our findings expand the
      morphologic spectrum of SMARCB1 (INI1) deficient sinonasal carcinoma. In
      addition, we show preliminarily that gonadal germ cell tumors with yolk sac tumor
      differentiation are not SMARCB1/INI1-deficient.

PMID- 29166821
TI  - The ribosomal DNA metaphase loop of Saccharomyces cerevisiae gets condensed upon
      heat stress in a Cdc14-independent TORC1-dependent manner.
AB  - Chromosome morphology in Saccharomyces cerevisiae is only visible at the
      microscopic level in the ribosomal DNA array (rDNA). The rDNA has been thus used
      as a model to characterize condensation and segregation of sister chromatids in
      mitosis. It has been established that the metaphase structure ("loop") depends,
      among others, on the condensin complex; whereas its segregation also depends on
      that complex, the Polo-like kinase Cdc5 and the cell cycle master phosphatase
      Cdc14. In addition, Cdc14 also drives rDNA hypercondensation in telophase.
      Remarkably, since all these components are essential for cell survival, their
      role on rDNA condensation and segregation was established by temperature
      sensitive (ts) alleles. Here, we show that the heat stress (HS) used to
      inactivate ts alleles (25 oC to 37 oC shift) causes rDNA loop condensation in
      metaphase-arrested wild type cells, a result that can also be mimicked by other
      stresses that inhibit the TORC1 pathway. Because this condensation might
      challenge previous findings with ts alleles, we have repeated classical
      experiments of rDNA condensation and segregation, yet using instead auxin-driven
      degradation alleles (aid alleles). We have undertaken the protein degradation at
      lower temperatures (25 oC) and concluded that the classical roles for condensin,
      Cdc5, Cdc14 and Cdc15 still prevailed. Thus, condensin degradation disrupts rDNA
      higher organization, Cdc14 and Cdc5 degradation precludes rDNA segregation and
      Cdc15 degradation still allows rDNA hypercompaction in telophase. Finally, we
      provide direct genetic evidence that this HS-mediated rDNA condensation is
      dependent on TORC1 but, unlike the one observed in anaphase, is independent of
      Cdc14.

PMID- 29166822
TI  - Myeloid cell leukemia 1 (MCL-1), an unexpected modulator of protein kinase
      signaling during invasion.
AB  - Myeloid cell leukemia-1 (MCL-1), closely related to B-cell lymphoma 2 (BCL-2),
      has a well-established role in cell survival and has emerged as an important
      target for cancer therapeutics. We have demonstrated that inhibiting MCL-1 is
      efficacious in suppressing tumour progression in pre-clinical models of breast
      cancer and revealed that in addition to its role in cell survival, MCL-1
      modulated cellular invasion. Utilizing a MCL-1-specific genetic antagonist, we
      found two possible mechanisms; firstly MCL-1 directly binds to and alters the
      phosphorylation of the cytoskeletal remodeling protein, Cofilin, a protein
      important for cytoskeletal remodeling during invasion, and secondly MCL-1
      modulates the levels SRC family kinases (SFKs) and their targets. These data
      provide evidence that MCL-1 activities are not limited to endpoints of
      extracellular and intracellular signaling culminating in cell survival as
      previously thought, but can directly modulate the output of SRC family kinases
      signaling during cellular invasion. Here we review the pleotropic roles of MCL-1
      and discuss the implications of this newly discovered effect on protein kinase
      signaling for the development of cancer therapeutics.

PMID- 29166823
TI  - Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1
      ATF4 pathway and induces autophagy via HSPB1.
AB  - Foot-and-mouth disease virus (FMDV) can result in economical destruction of
      cloven-hoofed animals. FMDV infection has been reported to induce
      macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy
      induction and effect of FMDV capsid protein on autophagy remain unknown. In the
      present study, we report that FMDV infection induced a complete autophagy process
      in the natural host cells of FMDV, and inhibition of autophagy significantly
      decreased FMDV production, suggesting that FMDV-induced autophagy facilitates
      viral replication. We found that the EIF2S1-ATF4 pathway was activated and the
      AKT-MTOR signaling pathway was inhibited by FMDV infection. We also observed that
      ultraviolet (UV)-inactivated FMDV can induce autophagy. Importantly, our work
      provides the first piece of evidence that expression of FMDV capsid protein VP2
      can induce autophagy through the EIF2S1-ATF4-AKT-MTOR cascade, and we found that
      VP2 interacted with HSPB1 (heat shock protein family B [small] member 1) and
      activated the EIF2S1-ATF4 pathway, resulting in autophagy and enhanced FMDV
      replication. In addition, we show that VP2 induced autophagy in a variety of
      mammalian cell lines and decreased aggregates of a model mutant HTT (huntingtin)
      polyglutamine expansion protein (HTT103Q). Overall, our results demonstrate that
      FMDV capsid protein VP2 induces autophagy through interaction with HSPB1 and
      activation of the EIF2S1-ATF4 pathway.

PMID- 29166824
TI  - Increased visceral adiposity index associated with sexual dysfunction in men.
AB  - OBJECTIVE: Visceral adipose index (VAI) is a novel parameter for the evaluation
      of visceral obesity. As we know that obesity is a risk factor for erectile
      dysfunction (ED). So, in this study, we compared the VAI levels between the men
      with ED and without ED. MATERIALS AND METHOD: A total of 177 men were included in
      the study. Ninety-five men with ED and 82 men without ED (control). All men were
      evaluated for ED by Index of Erectile Function-5 items (IIEF-5). VAI levels were
      calculated using body mass index, high density lipoprotein and tryglyceride
      levels. RESULTS: Mean age was 53.5 (38-69) in men who have ED and 53.1 (34-69) in
      control. The men with ED had higher body mass index (BMI), triglyceride (TG)
      levels, higher waist circumference (WC) and lower high-density lipoprotein
      cholesterol (HDL-C) levels. Mean VAI level was 5.18 +/- 2.50 in study group and
      3.47 +/- 1.76 in control goup, respectively. VAI levels were statistically higher
      in men with ED (p < .001). DISCUSSION: The simplicity of WC and BMI measurement
      and TG and HDL assessment, make VAI an easily applicable index for the evaluation
      of visceral fat dysfunction. VAI can be useful index for the evaluation and
      calculation of erectile dysfunction risk.

PMID- 29166825
TI  - Lifetime Consequences of Early-Life and Midlife Access to Health Insurance: A
      Review.
AB  - Over the past decade, the number of studies examining the effects of health
      insurance has grown rapidly, along with the breadth of outcomes considered. In
      light of growing research in this area and the intense policy focus on coverage
      expansions in the United States, there is need for an up-to-date and
      comprehensive literature review and synthesis of lessons learned. We reviewed 112
      experimental or quasi-experimental studies on the effects of health insurance
      prior to people becoming eligible for Medicare on a broad set of outcomes. Over
      the past decade, evidence related to the effect of increased access to health
      insurance has strengthened, illuminating that children and vulnerable adults are
      most likely to see health and economic benefits. We identified promising areas
      for future study in this active and burgeoning research area, noting benefit
      design of health insurance and outcomes such as government program participation
      and self-reported health status as targets.

PMID- 29166826
TI  - Polychlorinated biphenyls (PCBs) in River Niger, Nigeria: Occurrence,
      distribution and composition profiles.
AB  - Contamination of rivers with persistent organic pollutants (POPs) is an issue of
      current global concern. Polychlorinated biphenyls (PCBs) are POPs with origin
      from commercial, incineration and industrial sources. Hence, there is a need for
      monitoring their occurrence and distribution in the environment. This study
      assessed the occurrence, distribution and composition profiles of PCBs in River
      Niger, Nigeria. Surface and bottom water samples were collected in consecutive
      quarters for a period of 2 years, covering the beginning and end of the rainy
      seasons and the dry seasons, from five locations (Gurara, Lokoja, Onitsha, Brass
      and Nicolas) along River Niger. A total of 240 water samples were collected using
      a Van Dorn water sampler. EPA method 3510c was used with slight modifications for
      sample preparation and analysis. The PCBs were analysed using a Hewlett Packard
      GC 5890 Series 11 with electron capture detection, and confirmation was made
      using a Shimadzu GCMS QP2010. The higher molecular weight marker PCBs (?CB 138,
      153 and 180) were more dominant than the lighter homologues (?CB 28, 52 and 101),
      while commercial sources Co-PCBs (80.8 +/- 61.7 to 288.3 +/- 102.0 ng L-1) were
      more dominant than the incineration sources (34.9 +/- 3.82 to 75.5 +/- 65.2 ng L
      1). The POPs load in River Niger water varied in both time and space. In surface
      water of the River Niger, ?PCBs were higher during the rainy season, as a result
      of storm run-off from land-based sources. In the Brass and Nicolas Rivers during
      the dry season, the ?PCBs were higher during low tide. There was no noticeable
      pattern during the rainy season. It may be concluded from this study that the
      water of River Niger is not good for human consumption or abstraction of water
      from the river for drinking water treatment.

PMID- 29166827
TI  - Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in
      hippocampus but not in brain stem of mice.
AB  - The exploding popularity of mobile phones and their close proximity to the brain
      when in use has raised public concern regarding possible adverse effects from
      exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous
      system. Numerous studies have suggested that RF-EMF emitted by mobile phones can
      influence neuronal functions in the brain. Currently, there is still very limited
      information on what biological mechanisms influence neuronal cells of the brain.
      In the present study, we explored whether autophagy is triggered in the
      hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835
      MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks;
      afterward, the hippocampus and brain stem of mice were dissected and analyzed.
      Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated
      that several autophagic genes, which play key roles in autophagy regulation, were
      significantly upregulated only in the hippocampus and not in the brain stem.
      Expression levels of LC3B-II protein and p62, crucial autophagic regulatory
      proteins, were significantly changed only in the hippocampus. In parallel,
      transmission electron microscopy (TEM) revealed an increase in the number of
      autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed
      mice. The present study revealed that autophagy was induced in the hippocampus,
      not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks.
      These results could suggest that among the various adaptation processes to the RF
      EMF exposure environment, autophagic degradation is one possible mechanism in
      specific brain regions.

PMID- 29166828
TI  - Nurses' systems thinking competency, medical error reporting, and the occurrence
      of adverse events: a cross-sectional study.
AB  - BACKGROUND: Healthcare professionals' systems thinking is emphasized for patient
      safety. AIMS: To report nurses' systems thinking competency, and its relationship
      with medical error reporting and the occurrence of adverse events. DESIGN: A
      cross-sectional survey using a previously validated Systems Thinking Scale (STS),
      was conducted. METHODS: Nurses from two teaching hospitals were invited to
      participate in the survey. There were 407 (60.3%) completed surveys. RESULTS: The
      mean STS score was 54.5 (SD 7.3) out of 80. Nurses with higher STS scores were
      more likely to report medical errors (odds ratio (OR) = 1.05; 95% confidence
      interval (CI) = 1.02-1.08) and were less likely to be involved in the occurrence
      of adverse events (OR = 0.96; 95% CI = 0.93-0.98). CONCLUSIONS: Nurses showed
      moderate systems thinking competency. Systems thinking was a significant factor
      associated with patient safety. Impact Statement: The findings of this study
      highlight the importance of enhancing nurses' systems thinking capacity to
      promote patient safety.

PMID- 29166829
TI  - Rucaparib: A Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed
      Ovarian Cancer.
AB  - OBJECTIVE: To review the pharmacology, safety, efficacy, and the role of
      rucaparib in the treatment of relapsed, advanced ovarian cancer. SUMMARY: A total
      of 2 phase I/II trials and 1 phase II trial have evaluated the safety and
      efficacy of oral rucaparib in ovarian cancer. In patients with deleterious
      BRCA1/2 mutation, an overall response rate of 80% was achieved in the phase II
      trial Assessment of Rucaparib in Ovarian CancEr Trial 2 (ARIEL2). In the same
      trial, progression-free survival was higher in patients with BRCA1/2 mutation and
      BRCA wild types with high loss of heterozygosity (LOH) than BRCA wild types with
      low LOH. Rucaparib was found to be relatively well tolerated in clinical trials,
      with the most common adverse events being anemia, fatigue, and nausea.
      CONCLUSION: Rucaparib appears to be a safe and effective new option in the
      treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer. The role of
      rucaparib in this setting will likely expand and be further elucidated as results
      from several ongoing studies become available.

PMID- 29166830
TI  - The Role of Cefepime in the Treatment of Extended-Spectrum Beta-Lactamase
      Infections.
AB  - OBJECTIVE: To review the efficacy of cefepime for use in infections caused by
      extended-spectrum beta-lactamase (ESBL)-producing organisms. DATA SOURCES: A
      PubMed literature search (May 2000 to June 2017) was performed using the keyword
      cefepime and the MeSH terms beta-lactamases, cephalosporinases, and
      Enterobacteriaceae infections. STUDY SELECTION AND DATA EXTRACTION: All human,
      English language studies evaluating cefepime use for the treatment of ESBL
      producing Escherichia coli and Klebsiella pneumoniae infections were included.
      DATA SYNTHESIS: Studies assessing the use of cefepime for ESBL infections are
      few, and clinical studies are limited by design and sample size. The largest
      pharmacokinetic/pharmacodynamic study, a Monte Carlo simulation using data from
      the U.S. SENTRY antimicrobial surveillance program, evaluating cefepime use for
      infections due to ESBL-producing organisms found a 95% to 100% probability of
      target attainment with traditional cefepime dosing regimens. Most clinical
      studies found that patients treated with cefepime empirically and definitively
      had higher rates of mortality than those treated with carbapenems. However, in
      concordance with other studies reporting minimum inhibitory concentration (MIC)
      data, lower MICs were associated with lower mortality. CONCLUSIONS: Cefepime
      should be avoided for empiric treatment of suspected ESBL infections and should
      only be considered for definitive treatment if the MIC <=1 ug/mL. However, the
      site and severity of infection, local resistance patterns, and patient-specific
      risk factors should also help guide antimicrobial selection.

PMID- 29166831
TI  - Removal of organic matter and ammoniacal nitrogen from landfill leachate using
      the UV/H2O2 photochemical process.
AB  - This study investigates the effects of pH, H2O2 concentration and reaction time
      of the UV/H2O2 photochemical process on the removal of organic matter and ammonia
      from biologically pre-treated landfill leachates in anaerobic stabilization
      ponds. The results show that the concentration of H2O2 and the initial pH are
      significant factors, with no significant interaction between them. A pH of 3 is
      the optimum value for the UV/H2O2 process for the removal of organic matter,
      resulting in 51.63% chemical oxygen demand (COD) removal in addition to the
      removal of aromatic compounds. The N-NH3 removal showed little variation between
      pH values of 1, 5, 7, 11 and 13; the removal was on the order of 16.43 +/- 2.00%.
      The consumption of H2O2 was elevated at pH 9, 11 and 13; at these pH values, the
      average removal was 94.56 +/- 0.43%, compared to 43.07% at pH 3. First-order
      polynomial models and reaction times on the order of 15 min are sufficient for
      optimization studies and for evaluation of the effects of the studied parameters.
      The results of this study support the optimization of the UV/H2O2 process for the
      removal of organic matter and ammonia from landfill leachates.

PMID- 29166832
TI  - Conditioning exercises in ski jumping: biomechanical relationship of squat jumps,
      imitation jumps, and hill jumps.
AB  - As hill jumps are very time-consuming, ski jumping athletes often perform various
      imitation jumps during training. The performed jumps should be similar to hill
      jumps, but a direct comparison of the kinetic and kinematic parameters has not
      been performed yet. Therefore, this study aimed to correlate 11 common parameters
      during hill jumps (Oberstdorf Germany), squat jumps (wearing indoor shoes), and
      various imitation jumps (rolling 4 degrees , rolling flat, static; jumping
      equipment or indoor shoes) on a custom-built instrumented vehicle with a catch by
      the coach. During the performed jumps, force and video data of the take-off of 10
      athletes were measured. The imitation and squat jumps were then ranked. The main
      difference between the hill jumps and the imitation and squat jumps is the higher
      maximal force loading rate during the hill jumps. Imitation jumps performed on a
      rolling platform, on flat ground were the most similar to hill jumps in terms of
      the force-time, and leg joint kinematic properties. Thus, non-hill jumps with a
      technical focus should be performed from a rolling platform with a flat inrun
      with normal indoor shoes or jumping equipment, and high normal force loading
      rates should be the main focus of imitation training.

PMID- 29166833
TI  - Backward bifurcation and oscillations in a nested immuno-eco-epidemiological
      model.
AB  - This paper introduces a novel partial differential equation immuno-eco
      epidemiological model of competition in which one species is affected by a
      disease while another can compete with it directly and by lowering the first
      species' immune response to the infection, a mode of competition termed stress
      induced competition. When the disease is chronic, and the within-host dynamics
      are rapid, we reduce the partial differential equation model (PDE) to a three
      dimensional ordinary differential equation (ODE) model. The ODE model exhibits
      backward bifurcation and sustained oscillations caused by the stress-induced
      competition. Furthermore, the ODE model, although not a special case of the PDE
      model, is useful for detecting backward bifurcation and oscillations in the PDE
      model. Backward bifurcation related to stress-induced competition allows the
      second species to persist for values of its invasion number below one.
      Furthermore, stress-induced competition leads to destabilization of the
      coexistence equilibrium and sustained oscillations in the PDE model. We suggest
      that complex systems such as this one may be studied by appropriately designed
      simple ODE models.

PMID- 29166834
TI  - The entomopathogenic fungus Metarhizium robertsii communicates with the insect
      host Galleria mellonella during infection.
AB  - Parasitic fungi are the only pathogens that can infect insect hosts directly
      through their proteinaceous exoskeleton. Penetration of the cuticle requires the
      release of fungal enzymes, including proteinases, which act as virulence factors.
      Insects can sense fungal infections and activate innate immune responses,
      including the synthesis of antifungal peptides and proteinase inhibitors that
      neutralize the incoming proteinases. This well-studied host response is
      epigenetically regulated by histone acetylation/deacetylation. Here we show that
      entomopathogenic fungi can in turn sense the presence of insect-derived
      antifungal peptides and proteinase inhibitors, and respond by inducing the
      synthesis of chymotrypsin-like proteinases and metalloproteinases that degrade
      the host-derived defense molecules. The rapidity of this response is dependent on
      the virulence of the fungal strain. We confirmed the specificity of the pathogen
      response to host-derived defense molecules by LC/MS and RT-PCR analysis, and
      correlated this process with the epigenetic regulation of histone
      acetylation/deacetylation. This cascade of responses reveals that the coevolution
      of pathogens and hosts can involve a complex series of attacks and counterattacks
      based on communication between the invading fungal pathogen and its insect host.
      The resolution of this process determines whether or not pathogenesis is
      successful.

PMID- 29166835
TI  - Activation of STAT3-mediated CXCL12 up-regulation in the dorsal root ganglion
      contributes to oxaliplatin-induced chronic pain.
AB  - Oxaliplatin-induced chronic painful neuropathy is the most common dose-limiting
      adverse event that negatively affects cancer patients' quality of life. However,
      the underlying molecular mechanisms are still unclear. In the present study, we
      found that the intraperitoneal administration of oxaliplatin at 4 mg/kg for five
      consecutive days noticeably upregulated the expression of CXC motif ligand 12
      (CXCL12) in the dorsal root ganglion, and the intrathecal injection of an anti
      CXCL12 neutralizing antibody or CXCL12 siRNA attenuated the mechanical allodynia
      and thermal hyperalgesia induced by oxaliplatin. We also found that the signal
      transducers and transcription activator 3 (STAT3) was activated in the dorsal
      root ganglion, and inhibition of STAT3 with S3I-201 or the injection of AAV-Cre
      GFP into STAT3flox/flox mice prevented the upregulation of CXCL12 expression in
      the dorsal root ganglion and chronic pain following oxaliplatin administration.
      Double-label fluorescent immunohistochemistry findings also showed that p-STAT3
      was mainly localized in CXCL12-positive cells in the dorsal root ganglion.
      Furthermore, the results of a chromatin immunoprecipitation assay revealed that p
      STAT3 might be essential for oxaliplatin-induced CXCL12 upregulation via binding
      directly to the specific position of the CXCL12 gene promoter. Finally, we found
      that cytokine TNF-alpha and IL-1beta increases mediated the STAT3 activation
      following oxaliplatin treatment. Taken together, these findings suggested that
      the upregulation of CXCL12 via TNF-alpha/IL-1beta-dependent STAT3 activation
      contributes to oxaliplatin-induced chronic pain.

PMID- 29166836
TI  - Characterisation of Nav1.7 functional expression in rat dorsal root ganglia
      neurons by using an electrical field stimulation assay.
AB  - Background The Nav1.7 subtype of voltage-gated sodium channels is specifically
      expressed in sensory and sympathetic ganglia neurons where it plays an important
      role in the generation and transmission of information related to pain sensation.
      Human loss or gain-of-function mutations in the gene encoding Nav1.7 channels
      (SCN9A) are associated with either absence of pain, as reported for congenital
      insensitivity to pain, or with exacerbation of pain, as reported for primary
      erythromelalgia and paroxysmal extreme pain disorder. Based on this important
      human genetic evidence, numerous drug discovery efforts are ongoing in search for
      Nav1.7 blockers as a novel therapeutic strategy to treat pain conditions. Results
      We are reporting here a novel approach to study Nav1.7 function in cultured rat
      sensory neurons. We used live cell imaging combined with electrical field
      stimulation to evoke and record action potential-driven calcium transients in the
      neurons. We have shown that the tarantula venom peptide Protoxin-II, a known
      Nav1.7 subtype selective blocker, inhibited electrical field stimulation-evoked
      calcium responses in dorsal root ganglia neurons with an IC50 of 72 nM, while it
      had no activity in embryonic hippocampal neurons. The results obtained in the
      live cell imaging assay were supported by patch-clamp studies as well as by
      quantitative PCR and Western blotting experiments that confirmed the presence of
      Nav1.7 mRNA and protein in dorsal root ganglia but not in embryonic hippocampal
      neurons. Conclusions The findings presented here point to a selective effect of
      Protoxin-II in sensory neurons and helped to validate a new method for
      investigating and comparing Nav1.7 pharmacology in sensory versus central nervous
      system neurons. This will help in the characterisation of the selectivity of
      novel Nav1.7 modulators using native ion channels and will provide the basis for
      the development of higher throughput models for enabling pain-relevant phenotypic
      screening.

PMID- 29166837
TI  - Cisplatin alters the function and expression of N-type voltage-gated calcium
      channels in the absence of morphological damage of sensory neurons.
AB  - Platinum-based chemotherapeutic agents, such as cisplatin, are still frequently
      used for treating various types of cancer. Besides its high effectiveness,
      cisplatin has several serious side effects. One of the most common side effects
      is dorsal root ganglion (DRG) neurotoxicity. However, the mechanisms underlying
      this neurotoxicity are still unclear and controversially discussed. Cisplatin
      mediated modulation of voltage-gated calcium channels (VGCCs) in the DRG neurons
      has been shown to alter intracellular calcium homeostasis, a process critical for
      the induction of neurotoxicity. Using the whole-cell patch-clamp technique,
      immunostaining, behavioural experiments and electron microscopy (EM) of rat DRGs,
      we here demonstrate that cisplatin-induced neurotoxicity is due to functional
      alteration of VGCC, but not due to morphological damage. In vitro application of
      cisplatin (0.5 uM) increased N-type VGCC currents ( ICa(V)) in small DRG neurons.
      Repetitive in vivo administration of cisplatin (1.5 mg/kg, cumulative 12 mg/kg)
      increased the protein level of N-type VGCC over 26 days, with the protein level
      being increased for at least 14 days after the final cisplatin administration.
      Behavioural studies revealed that N-type VGCCs are crucial for inducing symptoms
      of cisplatin-related neuropathic pain, such as thermal and mechanical
      hyperalgesia. EM and histology showed no evidence of any structural damage,
      apoptosis or necrosis in DRG cells after cisplatin exposure for 26 days.
      Furthermore, no nuclear DNA damage in sensory neurons was observed. Here, we
      provide evidence for a mainly functionally driven induction of neuropathic pain
      by cisplatin.

PMID- 29166838
TI  - Immunohistochemical localization of nerve growth factor, tropomyosin receptor
      kinase A, and p75 in the bone and articular cartilage of the mouse femur.
AB  - Sequestration of nerve growth factor (NGF) significantly attenuates skeletal pain
      in both animals and humans. However, relatively little is known about the
      specific cell types that express NGF or its cognate receptors tropomyosin
      receptor kinase A (TrkA) and p75 in the intact bone and articular cartilage. In
      the present study, antibodies raised against NGF, TrkA, and p75 (also known as
      CD271) were used to explore the expression of these antigens in the non
      decalcified young mouse femur. In general, all three antigens displayed a
      remarkably restricted expression in bone and cartilage with less than 2% of all
      DAPI+ cells in the femur displaying expression of any one of the three antigens.
      Robust NGF immunoreactivity was found in mostly CD-31- blood vessel-associated
      cells, a small subset of CD-31+ endothelial cells, an unidentified group of cells
      located at the subchondral bone/articular cartilage interface, and a few
      isolated, single cells in the bone marrow. In contrast, p75 and TrkA were almost
      exclusively expressed by nerve fibers located nearby NGF+ blood vessels. The only
      non-neuronal expression of either p75 or TrkA in the femur was the expression of
      p75 by a subset of cells located in the deep and middle zone of the articular
      cartilage. Understanding the factors that tightly regulate the basal level of
      expression in normal bone and how the expression of NGF, TrkA, and p75 change in
      injury, disease, and aging may provide insights into novel therapies that can
      reduce skeletal pain and improve skeletal health.

PMID- 29166840
TI  - Ethics in nursing: A systematic review of the framework of evidence perspective.
AB  - AIM: To determine the current state of knowledge on nursing and ethics and to
      assess the knowledge and experience based on the evidence in this regard.
      BACKGROUND: Although ethics is at the center of the nursing profession and the
      ethical issues affecting nurses are given much importance, few studies have
      focused on professional ethics in nursing. In this respect, ethics has become a
      concept that contains controversial and ambiguous situations. DESIGN: The
      Preferred Reporting Items for Systematic Reviews and Meta-analyses guide, a basic
      search algorithm, was taken. DATA SOURCES: Cochrane, PubMed, CINAHL Complete,
      PsycINFO, and ULAKBIM from 2012 to 2016. REVIEW METHODS: Following a systematic
      search strategy, all papers were assessed in relation to inclusion criteria and
      type of study. When sufficient information was not available in the title and
      summary of the works, the necessary data were evaluated in full texts. RESULTS:
      This review was completed with 27 articles meeting the research criteria. The
      evaluation identified six themes: (1) ethics and nursing, (2) ethical
      difficulties/ethical dilemmas and nursing, (3) ethical competence and nursing,
      (4) professional ethics and nursing, (5) ethics, education, and nursing, and (6)
      ethics in health research. CONCLUSION: As a result of the review, a synthesis of
      high evidence-level research relating to nursing ethics was obtained. The
      emphasis was on the importance of further research and education so that the
      ethical aspects of nursing can be better understood throughout the studies.
      Nursing researchers' level of evidence on ethics and their orientation to high
      research design will shed light on uncertain and controversial aspects of the
      subject. Ethical consideration: Since this was a systematic review, no ethical
      approval was required. There is no conflict of interest in this literature
      review.

PMID- 29166839
TI  - The synergistic effect of treatment with triptolide and MK-801 in the rat
      neuropathic pain model.
AB  - Triptolide (T10), an active component of Tripterygium wilfordii Hook F, is
      reported to have potent anti-inflammatory and analgesic effects. Additionally, MK
      801, a noncompetitive N-methyl-D-aspartate receptor antagonist, can reduce
      glutamate toxicity and has a significant analgesic effect on chronic pain. In
      this study, we tested the possible synergistic analgesic ability by intrathecal
      administration of T10 and MK-801 for the treatment of neuropathic pain. Single
      T10 (3, 10, or 30 ug/kg), MK-801 (10, 30, or 90 ug/kg), or a combination of them
      were intrathecally administrated in rats with spinal nerve ligation. We found
      that single administration of T10 caused a slow-acting but long-term analgesic
      effect, while single administration of MK-801 caused a fast-acting but short-term
      effect. Administration of their combination showed obviously synergic analgesia
      and the 1:3 ratio of T10 to MK-801 reached the peak effect. Furthermore,
      application of T10 and/or MK-801 significantly inhibited the activation of
      microglia and astrocyte and phosphorylation of STAT3 and NR2B in the spinal
      dorsal horn induced by chronic neuropathic pain. Our data suggest that the
      combination of T10 and MK-801 may be a potentially novel strategy for treatment
      of neuropathic pain.

PMID- 29166841
TI  - Noninvasive optical and nuclear imaging of Staphylococcus-specific infection with
      a human monoclonal antibody-based probe.
AB  - Staphylococcus aureus infections are a major threat in healthcare, requiring
      adequate early-stage diagnosis and treatment. This calls for novel diagnostic
      tools that allow noninvasive in vivo detection of staphylococci. Here we
      performed a preclinical study to investigate a novel fully-human monoclonal
      antibody 1D9 that specifically targets the immunodominant staphylococcal antigen
      A (IsaA). We show that 1D9 binds invariantly to S. aureus cells and may further
      target other staphylococcal species. Importantly, using a human post-mortem
      implant model and an in vivo murine skin infection model, preclinical feasibility
      was demonstrated for 1D9 labeled with the near-infrared fluorophore IRDye800CW to
      be applied for direct optical imaging of in vivo S. aureus infections.
      Additionally, 89Zirconium-labeled 1D9 could be used for positron emission
      tomography imaging of an in vivo S. aureus thigh infection model. Our findings
      pave the way towards clinical implementation of targeted imaging of
      staphylococcal infections using the human monoclonal antibody 1D9.

PMID- 29166842
TI  - Measurement error correction in the least absolute shrinkage and selection
      operator model when validation data are available.
AB  - Measurement of serum biomarkers by multiplex assays may be more variable as
      compared to single biomarker assays. Measurement error in these data may bias
      parameter estimates in regression analysis, which could mask true associations of
      serum biomarkers with an outcome. The Least Absolute Shrinkage and Selection
      Operator (LASSO) can be used for variable selection in these high-dimensional
      data. Furthermore, when the distribution of measurement error is assumed to be
      known or estimated with replication data, a simple measurement error correction
      method can be applied to the LASSO method. However, in practice the distribution
      of the measurement error is unknown and is expensive to estimate through
      replication both in monetary cost and need for greater amount of sample which is
      often limited in quantity. We adapt an existing bias correction approach by
      estimating the measurement error using validation data in which a subset of serum
      biomarkers are re-measured on a random subset of the study sample. We evaluate
      this method using simulated data and data from the Tucson Epidemiological Study
      of Airway Obstructive Disease (TESAOD). We show that the bias in parameter
      estimation is reduced and variable selection is improved.

PMID- 29166843
TI  - Stagnant contraceptive sales after the Zika epidemic in Brazil.
AB  - OBJECTIVES: Our aim was to assess national hormonal and non-hormonal
      contraceptive sales in Brazil after the Zika virus outbreak. METHODS:
      Pharmaceutical companies based in Brazil provided data on monthly sales from
      September 2016 to June 2017. Data from both the public and private sectors were
      obtained about sales of registered, available modern contraceptive methods:
      combined oral contraceptive pill; progestin-only pill; vaginal and transdermal
      contraceptives; injectable contraceptives; long-acting reversible contraceptive
      (LARC) methods, including the copper-releasing intrauterine device, the
      levonorgestrel-releasing intrauterine system and the etonogestrel-releasing
      subdermal implant; and emergency contraceptive pills. RESULTS: Seventy-eight
      percent of sales comprised pills, patches and vaginal rings (11.1-13.8 million
      cycles/units per month), followed by emergency contraceptive pills (1.8-2.6
      million pills), injectables (1.2-1.4 million ampoules) and LARC methods (6500
      17,000 devices). CONCLUSIONS: The data showed much higher sales of short-acting
      methods compared with more effective LARC methods. The public sector needs to
      strengthen its focus on ensuring better access to LARC methods through a
      systematic approach ensuring regular supply, improved professional skills and
      better demand generation to couples wishing to avoid or delay pregnancy. In Zika
      virus-affected areas, many women of reproductive age may want to delay or
      postpone pregnancy by using an effective LARC method. The public sector should
      review its policies on LARC, as the need for these methods especially in Zika
      virus endemic areas may increase. A clear emphasis on quality in services, access
      and use is warranted.

PMID- 29166844
TI  - The phase model of psychotherapy outcome: Domain-specific trajectories of change
      in outpatient treatment.
AB  - OBJECTIVE: The Phase model of psychotherapy outcome assumes a log-linear
      trajectory of change and allows predictions about the three outcome domains of
      Well-being, Symptoms, and Interpersonal functioning. Although the model has been
      partly validated, little is known about the types of trajectories in the specific
      domains and about the transferability of the model to treatments of longer
      duration. This study tested whether the domain-specific change trajectories
      followed a log-linear curve as postulated by the Phase model. Furthermore, it was
      examined whether the speed of change differed between the domains. METHOD: Growth
      curves were modeled using hierarchical linear modeling on an outpatient sample (N
      = 351), with treatment duration averaging 52 sessions. RESULTS: A log-linear
      curve best explained the change trajectories of the domains Well-being and
      Symptoms as well as the Global score of psychopathology, whereas Interpersonal
      functioning tends to improve in a linear pattern. Estimated slopes were biggest
      for Well-being and smallest for Interpersonal functioning. CONCLUSIONS: In the
      present study, the predictions of the Phase model concerning multidimensional
      phases were validated. The finding that trajectories of change are not uniformly
      log-linear, but either log-linear or linear in a domain-specific manner, is
      partly inconsistent with the model.

PMID- 29166845
TI  - Identifying the minimum number of microsatellite loci needed to assess population
      genetic structure: A case study in fly culturing.
AB  - Small, isolated populations are constantly threatened by loss of genetic
      diversity due to drift. Such situations are found, for instance, in laboratory
      culturing. In guarding against diversity loss, monitoring of potential changes in
      population structure is paramount; this monitoring is most often achieved using
      microsatellite markers, which can be costly in terms of time and money when many
      loci are scored in large numbers of individuals. Here, we present a case study
      reducing the number of microsatellites to the minimum necessary to correctly
      detect the population structure of two Drosophila nigrosparsa populations. The
      number of loci was gradually reduced from 11 to 1, using the Allelic Richness
      (AR) and Private Allelic Richness (PAR) as criteria for locus removal. The effect
      of each reduction step was evaluated by the number of genetic clusters detectable
      from the data and by the allocation of individuals to the clusters; in the
      latter, excluding ambiguous individuals was tested to reduce the rate of
      incorrect assignments. We demonstrate that more than 95% of the individuals can
      still be correctly assigned when using eight loci and that the major population
      structure is still visible when using two highly polymorphic loci. The
      differences between sorting the loci by AR and PAR were negligible. The method
      presented here will most efficiently reduce genotyping costs when small sets of
      loci ("core sets") for long-time use in large-scale population screenings are
      compiled.

PMID- 29166846
TI  - Recurrent cerebral infarction in anterior and posterior circulation territories
      associated with persistent primitive hypoglossal artery and carotid artery
      dissection: a case report.
AB  - The persistent primitive hypoglossal artery (PPHA) is the second most common
      persistent carotid-vertebrobasilar anastomosis. We present a rare case of an 82
      year-old woman who diagnosed as acute cerebral infarction three times in both the
      anterior and posterior circulation territories with a right-sided PPHA and
      ipsilateral carotid artery dissection (CAD). Microembolus monitoring results
      suggested that microembolic caused by CAD associated with PPHA should be
      recognized as a possible cause of multiple infarctions in both the anterior and
      posterior circulation territories. For these patients, appropriate treatment
      measures should be taken for prevention of stroke recurrence.

PMID- 29166847
TI  - RETRACTED: Bucco-Lingual Crestal Bone Changes Around Implants Immediately Placed
      in Fresh Extraction Sockets in Association or not With Porcine Bone: A Non
      Blinded Randomized Controlled Trial in Humans (J Periodontol October 29, 2012
      [published online ahead of print]; doi: 10.1902/jop.2012.120396).

PMID- 29166848
TI  - Letter to the Editor: Re: Simultaneous Detection of Oral Pathogens in Subgingival
      Plaque and Prostatic Fluid of Men with Periodontal and Prostatic Disease.

PMID- 29166849
TI  - Peer Review Panel and Ad Hoc Reviewers for the Journal of Periodontology.

PMID- 29166850
TI  - Fishes in the desert: mitochondrial variation and phylogeography of Danakilia
      (Actinopterygii: Cichlidae) and Aphanius (Actinopterygii: Cyprinodontidae) in the
      Danakil Depression of northeastern Africa.
AB  - The Danakil Depression in northeastern Africa represents one of the harshest arid
      environments on Earth, yet two genera of fishes, Danakilia (Cichlidae) and
      Aphanius (Cyprinodontidae), share its sparse aquatic habitats. The evolutionary
      history of these fishes is investigated here in the context of genetic,
      geological and paleoenvironmental information. We collected samples from seven
      sites and assessed phylogeographic relationships using concatenated COI and cytb
      mtDNA genes. Danakilia morphospecies show low differentiation at mitochondrial
      markers, but variation is partitioned between a northern cluster containing D.
      dinicolai plus three undescribed riverine populations, and a southern cluster
      including two creek populations of D. franchettii separated by the hypersaline
      waters of Lake Afrera. Aphanius displayed four genetically distinct clades (A.
      stiassnyae in Lake Afrera; one distributed across the entire area; one in Lake
      Abaeded; and one in the Shukoray River), but without clear large-scale geographic
      structure. However, Danakil Aphanius are clearly differentiated from A. dispar
      sensu stricto from the Sinai Peninsula. Geological evidence suggests that after
      the Late Pleistocene closure of the Danakil-Red Sea connection, increased post
      glacial groundwater availability caused the formation of a brackish paleo-lake
      flooding the entire region below the -50 m contour. Fish populations previously
      isolated in coastal oases during glaciation were able to mix in the paleo-lake.
      Subsequently, in a more arid phase starting ~7300 BP, paleo-lake regression
      isolated fishes in separate drainages, triggering their still ongoing
      diversification.

PMID- 29166851
TI  - Novel mathematical model to estimate ball impact force in soccer.
AB  - To assess ball impact force during soccer kicking is important to quantify from
      both performance and chronic injury prevention perspectives. We aimed to verify
      the appropriateness of previous models used to estimate ball impact force and to
      propose an improved model to better capture the time history of ball impact
      force. A soccer ball was fired directly onto a force platform (10 kHz) at five
      realistic kicking ball velocities and ball behaviour was captured by a high-speed
      camera (5,000 Hz). The time history of ball impact force was estimated using
      three existing models and two new models. A new mathematical model that took into
      account a rapid change in ball surface area and heterogeneous ball deformation
      showed a distinctive advantage to estimate the peak forces and its occurrence
      times and to reproduce time history of ball impact forces more precisely, thereby
      reinforcing the possible mechanics of 'footballer's ankle'. Ball impact time was
      also systematically shortened when ball velocity increases in contrast to
      practical understanding for producing faster ball velocity, however, the aspect
      of ball contact time must be considered carefully from practical point of view.

PMID- 29166852
TI  - Unsupervised gene selection using biological knowledge : application in sample
      clustering.
AB  - BACKGROUND: Classification of biological samples of gene expression data is a
      basic building block in solving several problems in the field of bioinformatics
      like cancer and other disease diagnosis and making a proper treatment plan. One
      big challenge in sample classification is handling large dimensional and
      redundant gene expression data. To reduce the complexity of handling this high
      dimensional data, gene/feature selection plays a major role. RESULTS: The current
      paper explores the use of biological knowledge acquired from Gene Ontology
      database in selecting the proper subset of genes which can further participate in
      clustering of samples. The proposed feature selection technique is unsupervised
      in nature as it does not utilize any class label information in the process of
      gene selection. At the end, a multi-objective clustering approach is deployed to
      cluster the available set of samples in the reduced gene space. CONCLUSIONS:
      Reported results show that consideration of biological knowledge in gene
      selection technique not only reduces the feature space dimensionality in great
      extent but also improves the accuracy of sample classification. The obtained
      reduced gene space is validated using strong biological significance tests. In
      order to prove the supremacy of our proposed gene selection based sample
      clustering technique, a thorough comparative analysis has also been performed
      with state-of-the-art techniques.

PMID- 29166853
TI  - Proteomic insight into fruit set of cucumber (Cucumis sativus L.) suggests the
      cues of hormone-independent parthenocarpy.
AB  - BACKGROUND: Parthenocarpy is an excellent agronomic trait that enables crops to
      set fruit in the absence of pollination and fertilization, and therefore to
      produce seedless fruit. Although parthenocarpy is widely recognized as a hormone
      dependent process, hormone-insensitive parthenocarpy can also be observed in
      cucumber; however, its mechanism is poorly understood. To improve the global
      understanding of parthenocarpy and address the hormone-insensitive parthenocarpy
      shown in cucumber, we conducted a physiological and proteomic analysis of
      differently developed fruits. RESULTS: Physiological analysis indicated that the
      natural hormone-insensitive parthenocarpy of 'EC1' has broad hormone-inhibitor
      resistance, and the endogenous hormones in the natural parthenocarpy (NP) fruits
      were stable and relatively lower than those of the non-parthenocarpic cultivar
      '8419 s-1.' Based on the iTRAQ technique, 683 fruit developmental proteins were
      identified from NP, cytokinin-induced parthenocarpic (CP), pollinated and
      unpollinated fruits. Gene Ontology (GO) analysis showed that proteins detected
      from both set and aborted fruits were involved in similar biological processes,
      such as cell growth, the cell cycle, cell death and communication. Kyoto
      Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 'protein
      synthesis' was the major biological process that differed between fruit set and
      fruit abortion. Clustering analysis revealed that different protein expression
      patterns were involved in CP and NP fruits. Forty-one parthenocarpy-specialized
      DEPs (differentially expressed proteins) were screened and divided into two
      distinctive groups: NP-specialized proteins and CP-specialized proteins.
      Furthermore, qRT-PCR and western blot analysis indicated that NP-specialized
      proteins showed hormone- or hormone-inhibitor insensitive expression patterns in
      both ovaries and seedlings. CONCLUSIONS: In this study, the global molecular
      regulation of fruit development in cucumber was revealed at the protein level.
      Physiological and proteomic comparisons indicated the presence of hormone
      independent parthenocarpy and suppression of fruit abortion in cucumber. The
      proteomic analysis suggested that hormone-independent parthenocarpy is regulated
      by hormone-insensitive proteins such as the NP-specialized proteins. Moreover,
      the regulation of fruit abortion suppression may be closely related to protein
      synthesis pathways.

PMID- 29166854
TI  - A single dose of dezocine suppresses emergence agitation in preschool children
      anesthetized with sevoflurane-remifentanil.
AB  - BACKGROUND: Emergence agitation (EA) is a common phenomenon in preschool children
      during emergence from general anesthesia. This study evaluated the safety and
      efficacy of dezocine for emergence agitation in preschool children anesthetized
      with sevoflurane-remifentanil. METHODS: A total of 100 preschool children,
      scheduled for elective laparoscopic repair of an inguinal hernia by high ligation
      of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into
      two groups: Group C (n = 50) received Ringer's lactate 10 mL and Group D received
      Ringer's lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively. RESULTS:
      Incidence of EA, defined as a score >= 3 on Aono's four point scale or Pediatric
      Anesthesia Emergence Delirium (PAED) score >= 10 in the PACU (10% vs. 76%) and
      the percentage of patients with severe EA (PAED score >= 13) (12% vs. 76%) were
      significantly lower in Group D compared to Group C (P < 0.05). Mean Children and
      Infants Postoperative Pain Scale (CHIPPS) score was significantly lower in Group
      D compared to Group C (1.2 +/- 0.5 vs. 5.2 +/- 0.6; P < 0.05). Patients need for
      fentanyl (18% vs. 4%) or propofol rescue (20% vs. 0) was significantly greater in
      Group C compared to Group D. No significant differences in other relative aspects
      after surgery between groups. CONCLUSION: Administration of dezocine 0.1 mg/kg
      decreased the incidence and severity of EA in preschool children that had
      undergone laparoscopic repair of an inguinal hernia by high ligation of the
      hernia sac under sevoflurane-remifentanil anesthesia. TRIAL REGISTRATION: A
      single dose of dezocine suppresses emergence agitation in preschool children
      anesthetized with sevoflurane-remifentanil effectively: A double-blind,
      prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID:
      ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.

PMID- 29166855
TI  - Identification of differentially expressed genes in flower, leaf and bulb scale
      of Lilium oriental hybrid 'Sorbonne' and putative control network for scent
      genes.
AB  - BACKGROUND: Lily is an economically important plant, with leaves and bulbs
      consisting of overlapping scales, large ornamental flowers and a very large
      genome. Although it is recognized that flowers and bulb scales are modified
      leaves, very little is known about the genetic control and biochemical
      differentiation underlying lily organogenesis and development. Here we examined
      the differentially expressed genes in flower, leaf and scale of lily, using RNA
      sequencing, and identified organ-specific genes, including transcription factors,
      genes involved in photosynthesis in leaves, carbohydrate metabolism in bulb
      scales and scent and color production in flowers. RESULTS: Over 11Gb data were
      obtained and 2685, 2296, and 1709 differentially expressed genes were identified
      in the three organs, with 581, 662 and 977 unique DEGs in F-vs-S, L-vs-S and L-vs
      F comparisons. By functional enrichment analysis, genes likely to be involved in
      biosynthetic pathways leading to floral scent production, such as 1-deoxy-D
      xylulose-5-phosphate synthase (DXS), 3-ketoacyl-CoA thiolase (KAT), hydroperoxide
      lyase (HPL), geranylgeranyl pyrophosphate (GGPP) 4-hydroxy-3-methylbut-2-en-1-yl
      diphosphate (HDS) and terpene synthase (TPS), and floral color genes, such as
      dihydroflavonol 4-reductase (DFR), chalcone synthase (CHS), chalcone isomerase
      (CHI), flavonol synthase (FLS) were identified. Distinct groups of genes that
      participate in starch and sucrose metabolism, such as sucrose synthase (SS),
      invertase (INV), sucrose phosphate synthase (SPS), starch synthase (SSS), starch
      branching enzyme (SBE), ADP-glucose pyrophosphorylase (AGP) andbeta-amylase (BAM)
      and photosynthesis genes (Psa, Psb, Pet and ATP) were also identified. The
      expression of six floral fragrance-related DGEs showed agreement between qRT-PCR
      results and RPKM values, confirming the value of the data obtained by RNA-seq. We
      obtained the open reading frame of the terpene synthase gene from Lilium
      'Sorbonne', designated LsTPS, which had 99.55% homology to transcript
      CL4520.Contig5_All. In addition, 54, 48 and 50 differently expressed
      transcription factor were identified by pairwise comparisons between the three
      organs and a regulatory network for monoterpene biosynthesis was constructed.
      CONCLUSIONS: Analysis of differentially expressed genes in flower, leaf and bulb
      scale of lily, using second generation sequencing technology, yielded detailed
      information on lily metabolic differentiation in three organs. Analysis of the
      expression of flower scent biosynthesis genes has provided a model for the
      regulation of the pathway and identified a candidate gene encoding an enzyme
      catalyzing the final step in scent production. These digital gene expression
      profiles provide a valuable and informative database for the further
      identification and analysis of structural genes and transcription factors in
      different lily organs and elucidation of their function.

PMID- 29166856
TI  - Glycyl-alanyl-histidine protects PC12 cells against hydrogen peroxide toxicity.
AB  - BACKGROUND: Peptides with cytoprotective functions, including antioxidants and
      anti-infectives, could be useful therapeutics. Carnosine, beta-alanine-histidine,
      is a dipeptide with anti-oxidant properties. Tripeptides of Ala-His-Lys, Pro-His
      His, or Tyr-His-Tyr are also of interest in this respect. RESULTS: We synthesized
      several histidine-containing peptides including glycine or alanine, and tested
      their cytoprotective effects on hydrogen peroxide toxicity for PC12 cells. Of all
      these peptides (Gly-His-His, Ala-His-His, Ala-His-Ala, Ala-Ala-His, Ala-Gly-His,
      Gly-Ala-His (GAH), Ala-His-Gly, His-Ala-Gly, His-His-His, Gly-His-Ala, and Gly
      Gly-His), GAH was found to have the strongest cytoprotective activity. GAH
      decreased lactate dehydrogenase (LDH) leakage, apoptosis, morphological changes,
      and nuclear membrane permeability changes against hydrogen peroxide toxicity in
      PC12 cells. The cytoprotective activity of GAH was superior to that of carnosine
      against hydrogen peroxide toxicity in PC12 cells. GAH also protected PC12 cells
      against damage caused by actinomycin D and staurosporine. Additionally, it was
      found that GAH also protected SH-SY5Y and Jurkat cells from damage caused by
      hydrogen peroxide, as assessed by LDH leakage. CONCLUSION: Thus, a novel
      tripeptide, GAH, has been identified as having broad cytoprotective effects
      against hydrogen peroxide-induced cell damage.

PMID- 29166857
TI  - Genome analysis of the foxtail millet pathogen Sclerospora graminicola reveals
      the complex effector repertoire of graminicolous downy mildews.
AB  - BACKGROUND: Downy mildew, caused by the oomycete pathogen Sclerospora
      graminicola, is an economically important disease of Gramineae crops including
      foxtail millet (Setaria italica). Plants infected with S. graminicola are
      generally stunted and often undergo a transformation of flower organs into leaves
      (phyllody or witches' broom), resulting in serious yield loss. To establish the
      molecular basis of downy mildew disease in foxtail millet, we carried out whole
      genome sequencing and an RNA-seq analysis of S. graminicola. RESULTS: Sequence
      reads were generated from S. graminicola using an Illumina sequencing platform
      and assembled de novo into a draft genome sequence comprising approximately 360
      Mbp. Of this sequence, 73% comprised repetitive elements, and a total of 16,736
      genes were predicted from the RNA-seq data. The predicted genes included those
      encoding effector-like proteins with high sequence similarity to those previously
      identified in other oomycete pathogens. Genes encoding jacalin-like lectin-domain
      containing secreted proteins were enriched in S. graminicola compared to other
      oomycetes. Of a total of 1220 genes encoding putative secreted proteins, 91
      significantly changed their expression levels during the infection of plant
      tissues compared to the sporangia and zoospore stages of the S. graminicola
      lifecycle. CONCLUSIONS: We established the draft genome sequence of a downy
      mildew pathogen that infects Gramineae plants. Based on this sequence and our
      transcriptome analysis, we generated a catalog of in planta-induced candidate
      effector genes, providing a solid foundation from which to identify the effectors
      causing phyllody.

PMID- 29166858
TI  - ADAGE signature analysis: differential expression analysis with data-defined gene
      sets.
AB  - BACKGROUND: Gene set enrichment analysis and overrepresentation analyses are
      commonly used methods to determine the biological processes affected by a
      differential expression experiment. This approach requires biologically relevant
      gene sets, which are currently curated manually, limiting their availability and
      accuracy in many organisms without extensively curated resources. New feature
      learning approaches can now be paired with existing data collections to directly
      extract functional gene sets from big data. RESULTS: Here we introduce a method
      to identify perturbed processes. In contrast with methods that use curated gene
      sets, this approach uses signatures extracted from public expression data. We
      first extract expression signatures from public data using ADAGE, a neural
      network-based feature extraction approach. We next identify signatures that are
      differentially active under a given treatment. Our results demonstrate that these
      signatures represent biological processes that are perturbed by the experiment.
      Because these signatures are directly learned from data without supervision, they
      can identify uncurated or novel biological processes. We implemented ADAGE
      signature analysis for the bacterial pathogen Pseudomonas aeruginosa. For the
      convenience of different user groups, we implemented both an R package
      (ADAGEpath) and a web server ( http://adage.greenelab.com ) to run these
      analyses. Both are open-source to allow easy expansion to other organisms or
      signature generation methods. We applied ADAGE signature analysis to an example
      dataset in which wild-type and ?anr mutant cells were grown as biofilms on the
      Cystic Fibrosis genotype bronchial epithelial cells. We mapped active signatures
      in the dataset to KEGG pathways and compared with pathways identified using GSEA.
      The two approaches generally return consistent results; however, ADAGE signature
      analysis also identified a signature that revealed the molecularly supported link
      between the MexT regulon and Anr. CONCLUSIONS: We designed ADAGE signature
      analysis to perform gene set analysis using data-defined functional gene
      signatures. This approach addresses an important gap for biologists studying non
      traditional model organisms and those without extensive curated resources
      available. We built both an R package and web server to provide ADAGE signature
      analysis to the community.

PMID- 29166859
TI  - Divergent clades or cryptic species? Mito-nuclear discordance in a Daphnia
      species complex.
AB  - BACKGROUND: Genetically divergent cryptic species are frequently detected by
      molecular methods. These discoveries are often a byproduct of molecular barcoding
      studies in which fragments of a selected marker are used for species
      identification. Highly divergent mitochondrial lineages and putative cryptic
      species are even detected in intensively studied animal taxa, such as the
      crustacean genus Daphnia. Recently, eleven such lineages, exhibiting genetic
      distances comparable to levels observed among well-defined species, were recorded
      in the D. longispina species complex, a group that contains several key taxa of
      freshwater ecosystems. We tested if three of those lineages represent indeed
      distinct species, by analyzing patterns of variation of ten nuclear
      microsatellite markers in six populations. RESULTS: We observed a discordant
      pattern between mitochondrial and nuclear DNA, as all individuals carrying one of
      the divergent mitochondrial lineages grouped at the nuclear level with
      widespread, well-recognized species coexisting at the same localities (Daphnia
      galeata, D. longispina, and D. cucullata). CONCLUSIONS: A likely explanation for
      this pattern is the introgression of the mitochondrial genome of undescribed taxa
      into the common species, either in the distant past or after long-distance
      dispersal. The occurrence of highly divergent but rare mtDNA lineages in the gene
      pool of widespread species would suggest that hybridization and introgression in
      the D. longispina species complex is frequent even across large phylogenetic
      distances, and that discoveries of such distinct clades must be interpreted with
      caution. However, maintenance of ancient polymorphisms through selection is
      another plausible alternative that may cause the observed discordance and cannot
      be entirely excluded.

PMID- 29166860
TI  - msaABCR operon is involved in persister cell formation in Staphylococcus aureus.
AB  - BACKGROUND: Persister cells comprise a phenotypic variant that shows extreme
      antibiotic tolerance resulting in treatment failures of bacterial infections.
      While this phenomenon has posed a great threat in public health, mechanisms
      underlying their formation in Staphylococcus aureus remain largely unknown.
      Increasing evidences of the presence of persister cells in recalcitrant
      infections underscores the great urgency to unravel the mechanism by which these
      cells develop. Previously, we characterized msaABCR operon that plays roles in
      regulation of virulence, biofilm development and antibiotic resistance. We also
      characterized the function of MsaB protein and showed that MsaB is a putative
      transcription factor that binds target DNA in response to nutrients availability.
      RESULTS: In this study, we compared the number of persister cell in wild type,
      msaABCR deletion mutant and the complemented strain in two backgrounds USA300 LAC
      and Mu50. Herein, we report that msaABCR deletion mutant forms significantly less
      number of persister cells relative to wild type after challenge with various
      antibiotics in planktonic and biofilm growth conditions. Complementation of the
      msaABCR operon restored wild type phenotype. Combined antibiotic therapy along
      with msaABCR deletion significantly improves the killing kinetics of stationary
      phase and biofilm S. aureus cells. Transcriptomics analysis showed that msaABCR
      regulates several metabolic genes, transcription factors, transporters and
      enzymes that may play role in persister cells formation, which we seek to define
      in the future. CONCLUSIONS: This study presented a new regulator, msaABCR operon,
      that is involved in the persister cells formation, which is a poorly understood
      in S. aureus. Indeed, we showed that msaABCR deletion significantly reduces the
      persister cells formation in all growth phases tested. Although, we have not yet
      defined the mechanism, we have shown that msaABCR regulates several metabolic,
      transporters, and extracellular proteases genes that have been previously linked
      with persister cells formation in other bacterial systems. Taken together, this
      study showed that inactivation of the msaABCR operon enhances the effectiveness
      of antibiotics for the treatment of S. aureus infections, especially in context
      of persister cells.

PMID- 29166861
TI  - Comprehensive transcriptome analysis reveals distinct regulatory programs during
      vernalization and floral bud development of orchardgrass (Dactylis glomerata L.).
AB  - BACKGROUND: Vernalization and the transition from vegetative to reproductive
      growth involve multiple pathways, vital for controlling floral organ formation
      and flowering time. However, little transcription information is available about
      the mechanisms behind environmental adaption and growth regulation. Here, we used
      high-throughput sequencing to analyze the comprehensive transcriptome of Dactylis
      glomerata L. during six different growth periods. RESULTS: During vernalization,
      4689 differentially expressed genes (DEGs) significantly increased in abundance,
      while 3841 decreased. Furthermore, 12,967 DEGs were identified during booting
      stage and flowering stage, including 7750 up-regulated and 5219 down-regulated
      DEGs. Pathway analysis indicated that transcripts related to circadian rhythm,
      photoperiod, photosynthesis, flavonoid biosynthesis, starch, and sucrose
      metabolism changed significantly at different stages. Coexpression and weighted
      correlation network analysis (WGCNA) analysis linked different stages to
      transcriptional changes and provided evidence of inner relation modules
      associated with signal transduction, stress responses, cell division, and
      hormonal transport. CONCLUSIONS: We found enrichment in transcription factors
      (TFs) related to WRKY, NAC, AP2/EREBP, AUX/IAA, MADS-BOX, ABI3/VP1, bHLH, and the
      CCAAT family during vernalization and floral bud development. TFs expression
      patterns revealed intricate temporal variations, suggesting relatively separate
      regulatory programs of TF modules. Further study will unlock insights into the
      ability of the circadian rhythm and photoperiod to regulate vernalization and
      flowering time in perennial grass.

PMID- 29166862
TI  - Gastric stump carcinoma as a long-term complication of pancreaticoduodenectomy:
      report of two cases and review of the English literature.
AB  - BACKGROUND: Gastric stump carcinoma is an exceptional and poorly known long-term
      complication after pancreaticoduodenectomy. CASES PRESENTATION: Two patients
      developed gastric stump carcinoma 19 and 10 years after pancreaticoduodenectomy
      for malignant ampulloma and total pancreaticoduodenectomy for pancreatic
      adenocarcinoma, respectively. Both patients had pT4 signet-ring cell carcinoma
      involving the gastrojejunostomy site that was revealed by bleeding or
      obstruction. Patient 1 is alive and remains disease-free 36 months after
      completion gastrectomy. Patient 2 presented with peritoneal carcinomatosis and
      died after palliative surgery. We identified only 3 others cases in the English
      literature. CONCLUSIONS: Prolonged biliary reflux might be the most important
      risk factor of gastric stump carcinoma following pancreaticoduodenectomy. Its
      incidence might increase in the future due to prolonged survival observed after
      pancreaticoduodenectomy for benign and premalignant lesions.

PMID- 29166863
TI  - Characterization of the inner membrane protein BB0173 from Borrelia burgdorferi.
AB  - BACKGROUND: The bacterial spirochete Borrelia burgdorferi is the causative agent
      of the most commonly reported arthropod-borne illness in the United States, Lyme
      disease. A family of proteins containing von Willebrand Factor A (VWFA) domains
      adjacent to a MoxR AAA+ ATPase have been found to be highly conserved in the
      genus Borrelia. Previously, a VWFA domain containing protein of B. burgdorferi,
      BB0172, was determined to be an outer membrane protein capable of binding
      integrin alpha3beta1. In this study, the characterization of a new VWFA domain
      containing membrane protein, BB0173, is evaluated in order to define the location
      and topology of this multi-spanning membrane protein. In addition, functional
      predictions are made. RESULTS: Our results show that BB0173, in contrast to
      BB0172, is an inner membrane protein, in which the VWFA domain is exposed to the
      periplasmic space. Further, BB0173 was predicted to have an aerotolerance
      regulator domain, and expression of BB0173 and the surrounding genes was
      evaluated under aerobic and microaerophilic conditions, revealing that these
      genes are downregulated under aerobic conditions. Since the VWFA domain
      containing proteins of B. burgdorferi are highly conserved, they are likely
      required for survival of the pathogen through sensing diverse environmental
      oxygen conditions. CONCLUSIONS: Presently, the complex mechanisms that B.
      burgdorferi uses to detect and respond to environmental changes are not
      completely understood. However, studying the mechanisms that allow B. burgdorferi
      to survive in the highly disparate environments of the tick vector and mammalian
      host could allow for the development of novel methods of preventing acquisition,
      survival, or transmission of the spirochete. In this regard, a putative membrane
      protein, BB0173, was characterized. BB0173 was found to be highly conserved
      across pathogenic Borrelia, and additionally contains several truly transmembrane
      domains, and a Bacteroides aerotolerance-like domain. The presence of these
      functional domains and the highly conserved nature of this protein, strongly
      suggests a required function of BB0173 in the survival of B. burgdorferi.

PMID- 29166864
TI  - Prevalence and risk factors for depression and anxiety in Chinese patients with
      Parkinson disease.
AB  - BACKGROUND: Anxiety and depression are common in Parkinson disease and both are
      important determinants of quality of life in patients. Several risk factors are
      identified but few research have investigated general and Parkinson's disease
      (PD)-specific factors comprehensively. The aim of this work was to explore PD
      specific and -non-specific risk factors for PD with depression or anxiety.
      METHODS: A cross-sectional survey was performed in 403 patients with PD.
      Multivariate logistic analysis was used to investigate the prevalence and risk
      factors for the depression and anxiety in PD. The data of patients included
      demographic information, medicine history, disease duration, age at onset (AAO),
      family history, anti-parkinsonism drug, modified Hoehn and Yahr staging (H-Y)
      stage, scales of motor and non-motor symptoms and substantia nigra (SN) echogenic
      areas. RESULTS: 403 PD patients were recruited in the study. Depression and
      anxiety were present in 11.17% and 25.81% respectively. Marital status, tumor,
      higher Movement Disorder Society-sponsored revision of the Unified Parkinson's
      Disease Rating Scale (MDS-UPDRS) II score, dyskinesia, higher Hamilton Anxiety
      Rating Scale (HARS) score and lower the Parkinson's disease sleep scale (PDSS)
      score were associated with depression in PD. female gender, higher rapid eye
      movement behavior disorder Questionnaire-Hong Kong (RBD-HK) score, higher
      Hamilton Deprssion Rating Scale (HAMD) score, higher the scale for outcomes in PD
      for autonomic symptoms (SCOPA-AUT)score and larger SN echogenic areas were
      associated with anxiety. Neither depression nor anxiety was related to any anti
      parkinsonism drugs. CONCLUSIONS: The prevalence of depression and anxiety in the
      current PD patients was 11.17% and 25.81% respectively. Disease of tumor,
      currently having no partner, severer motor function, dyskinesia, poorer sleep
      quality and anxiety were risk factors for PD with depression. Female, depression,
      rapid eye movement behavior disorder (RBD), autonomic dysfunction and larger SN
      area were risk factors for PD with anxiety.

PMID- 29166865
TI  - King's Health Partners' Prostate Cancer Biobank (KHP PCaBB).
AB  - The KHP PCaBB was established in 2013 and recruits donors from the Urology or
      Oncology Departments at Guy's Hospital in London (UK). Prostate cancer patients
      may be approached to give their consent for biobanking at any point in their
      treatment pathway, which allows residual material from their earlier diagnosis to
      be transferred and used by the Biobank. Currently, patients are specifically
      asked to donate samples of blood and surplus prostate tissue as well as
      permitting access to their clinical and pathological data that continues to be
      added throughout the course of their disease. Between 2013 and 2015, 549 prostate
      cancer patients gave their consent to the biobank and, the tissue repository
      collected 489 blood samples, 120 frozen prostate tissue samples and 1064 formalin
      fixed paraffin embedded diagnostic blocks.Prostate cancer has become a chronic
      disease in a large proportion of men, with many men receiving multiple subsequent
      treatments, and their treatment trajectory often spanning over decades.
      Therefore, this resource aims to provide an ideal research platform to explore
      potential variations in treatment response as well as disease markers in the
      different risk categories for prostate cancer.A recent audit of the KHP PCaBB
      revealed that between 2013 and 2015, 1796 patients were diagnosed with prostate
      cancer at King's Health Partners (KHP), out of which 549 (30.6%) gave their
      consent to KHP PCaBB. Comparisons between demographic and clinical
      characteristics of patients who had consented compared to the total patient
      population revealed that the KHP PCaBB is demographically representative of the
      total prostate cancer patient population seen in Guy's and St Thomas' NHS
      Foundation Trust (GSTT). We observed no differences in distribution of ethnicity
      (p = 0.507) and socioeconomic status (p = 0.097). Some differences were observed
      in clinical characteristics, specifically with treatment type - which differed
      significantly between the patients who had given consent and total patient
      population.The KHP PCaBB has thereby amassed a rich data and tissue repository
      that is largely reflective of both the demographic and clinical diversity within
      the total prostate cancer patient population seen at KHP, making it an ideal
      platform for prostate cancer research.

PMID- 29166866
TI  - The risk and survival outcome of subsequent primary colorectal cancer after the
      first primary colorectal cancer: cases from 1973 to 2012.
AB  - BACKGROUND: Among colorectal cancer (CRC) survivors, how the prior tumor location
      affects the risk of subsequent primary colorectal cancer (SPCRC) and the outcome
      of those suffering from SPCRC remain unknown. METHODS: CRC cases diagnosed from
      1973 to 2012 were screened for SPCRC development using the Surveillance,
      Epidemiology, and End Results database. The relative risk of SPCRC was estimated
      using the standardized incidence ratio. Survivals were analyzed using the Kaplan
      Meier and Cox regression model. RESULTS: The overall risk of SPCRC increased by
      27% in CRC survivors compared to that of the general population. The risk
      increased in patients with both prior right colon cancer (RCC) and left colon
      cancer (LCC), and was concentrated in the first 5 years after the prior
      diagnosis, and among young patients. Among the 6701 SPCRC patients identified,
      patients with prior RCC were more likely to be elderly, female, and with more low
      or undifferentiated disease than those with prior LCC or rectal cancer (ReC). The
      overall survivals differed by both prior tumor location (P < 0.0001) and age (P <
      0.0001), and the difference by tumor location remained significant when adjusted
      or stratified by any other potential prognostic factor except age. The cancer
      specific survivals differed by age (P < 0.0001) rather than by prior tumor
      location (P = 0.455). CONCLUSIONS: The overall risk of SPCRC increased among
      patients with both prior RCC and LCC, but not among those with ReC. The different
      survival outcomes in CRC survivors suffering from SPCRC were largely explained by
      the patient age but not by the prior tumor location.

PMID- 29166867
TI  - Clinical and virological factors associated with gastrointestinal symptoms in
      patients with acute respiratory infection: a two-year prospective study in
      general practice medicine.
AB  - BACKGROUND: Gastrointestinal (GI) symptoms, such as diarrhea, vomiting, abdominal
      pain and nausea are not an uncommon manifestation of an acute respiratory
      infection (ARI). We therefore evaluated clinical and microbiological factors
      associated with the presence of GI symptoms in patients consulting a general
      practitioner (GP) for ARI. METHODS: Nasopharyngeal swabs, stool specimens and
      clinical data from patients presenting to GPs with an ARI were prospectively
      collected during two winter seasons (2014-2016). Samples were tested by
      quantitative real-time PCR for 12 respiratory pathogen groups and for 12 enteric
      pathogens. RESULTS: Two hundred and four of 331 included patients (61.6%) were
      positive for at least one respiratory pathogen. Sixty-nine stools (20.8%) were
      positive for at least one pathogen (respiratory and/or enteric). GI symptoms were
      more likely declared in case of laboratory confirmed-enteric infection (adjusted
      odds ratio (aOR) = 3.2; 95% confidence interval [CI] [1.2-9.9]; p = 0.02) or
      human coronavirus (HCoV) infection (aOR = 2.7; [1.2-6.8]; p = 0.02). Consumption
      of antipyretic medication before the consultation seemed to reduce the risk of
      developing GI symptoms for patients with laboratory-confirmed influenza (aOR =
      0.3; [0.1-0.6]; p = 0.002). CONCLUSIONS: The presence of GI symptoms in ARI
      patients could not be explained by the detection of respiratory pathogens in
      stools. However, the detection of enteric pathogens in stool samples could
      explained by the presence of GI symptoms in some of ARI cases. The biological
      mechanisms explaining the association between the presence of HCoVs in
      nasopharynx and GI symptoms need to be explored.

PMID- 29166868
TI  - Prevalence of ESR1 E380Q mutation in tumor tissue and plasma from Japanese breast
      cancer patients.
AB  - BACKGROUND: ESR1 mutations have attracted attention as a potentially important
      marker and treatment target in endocrine therapy-resistant breast cancer
      patients. The E380Q mutation, which is one of the ESR1 mutations, is associated
      with estradiol (E2) hypersensitivity, increased DNA binding to the estrogen
      response element, and E2-independent constitutive trans-activation activity, but
      its frequency in ESR1 mutations remains unknown. The present study aimed to
      investigate the E380Q mutation in comparison with the other representative ESR1
      mutations. METHODS: We screened a total of 62 patients (66 tumor tissues and 69
      plasma cell-free DNA (cfDNA)) to detect ESR1 mutations (E380Q, Y537S, Y537N,
      Y537C, and D538G) using droplet-digital polymerase chain reaction. Plasma was
      collected at more than two points of the clinical course, in whom changes of ESR1
      mutations under treatment were investigated. RESULTS: We detected ESR1 mutations
      in 21% (12/57) of MBCs. The E380Q ESR1 mutation was found in 16% (2/12) and the
      other ESR1 LBD mutations were five (41.6%) of Y537S, and four each (33.3%) of
      D538G, Y537N, and Y537C, in 12 ESR1 mutant breast cancer patients. Five tumors
      had multiple ESR1 mutations: three had double ESR1 mutations; Y537S/E380Q,
      Y37S/Y537C, and Y537S/D538G, and two had triple ESR1 mutations;
      Y537S/Y537N/D538G. In plasma cfDNA analysis, the E380Q mutation was not detected,
      but increases in other ESR1 mutations were detected in 46.2% (6/13) of MBC
      patients under treatment. CONCLUSIONS: We have shown that there are distinct
      populations of ESR1 mutations in metastatic tissue and plasma. Each ESR1 mutation
      may have different clinical significance, and it will be necessary to investigate
      them all.

PMID- 29166869
TI  - Multimodal imaging of retinal pigment epithelial detachments in patients with C3
      glomerulopathy: case report and review of the literature.
AB  - BACKGROUND: To describe the optical coherence tomography angiograhy (OCTA) of
      drusenoid pigment epithelial detachments (PEDs) in a woman affected by Complement
      3 (C3) glomerulopathy, which represents a spectrum of glomerular diseases
      characterized on fluorescent microscopy by C3 accumulation with absent, or
      scanty, immunoglobulin deposits. It is due to acquired or genetically defective
      alternative pathway control and is generally associated with drusen-like deposits
      in Bruch's membrane, as well as choriocapillaris. These retinal lesions can be
      associated with choroidal neovascularization and central serous chorioretinopathy
      (CSCR). OCTA is useful to detect neovascularization without injecting a contrast
      product, particularly in these patients who may have renal insufficiency. CASE
      PRESENTATION: A 28-year-old woman affected by C3 glomerulpathy was diagnosed with
      asymptomatic multiple bilateral PEDs during a routine ophthalmologic
      consultation. To better characterize the lesions, multimodal imaging was
      performed and included: optic coherence tomography (OCT), en-face OCT, OCTA,
      fluorescence and indocyanine angiography. The OCTA clearly identified vascular
      network rarefaction with decreased choriocapillary vascularization. It confirmed
      that PEDs associated with C3 glomerulonephritis are not vascularized, but rather
      of serous type. CONCLUSIONS: Patients affected by C3 glomerulopathy can develop
      neovascular membranes as retinal complications of pigment epithelial detachments.
      Optical coherence angiography may be indicated to identify this complication,
      without injecting any contrast product that could produce further kidney damage.

PMID- 29166870
TI  - Recruiting former melanoma patients via hospitals in comparison to office-based
      dermatologists in a register-based cohort study that required indirect contact.
AB  - BACKGROUND: There are detailed reviews about different recruitment strategies,
      but not with regard to differences between recruitment of hospital-based versus
      office-based physicians. Within this study, the two different recruitment schemes
      are compared. Advantages and disadvantages of different ways of recruitment in
      registry-based studies are discussed. METHODS: In a cross-sectional cancer
      registry-based study, long-term melanoma patients were contacted by
      dermatologists rather than directly by the registry on the basis of the legal
      situation. Logistic regression models and generalized estimating equations were
      used to assess effects of various patient and physician characteristics on
      participation and data quality. Especially differences between hospital-based
      versus office-based dermatologists are evaluated. RESULTS: Seventy two out of 112
      contacted dermatologists took part in the study (64.3%). The cooperation
      proportion was 52.2% (689 participants/1320 contacted patients). Participants and
      non-participants differed regarding age and sex, but not regarding other social
      demographic factors and cancer stage. We did not observe a difference in patient
      participation between hospital-based versus office-based dermatologists (OR 1.08
      [CI 0.84-1.39]; p = 0.57). However, medical data provided by the cancer registry
      were better for participants registered and recruited by hospitals. CONCLUSIONS:
      In cohort studies with epidemiological cancer registries, recruitment via
      physicians has potential disadvantages and is more complex. If this indirect way
      of contact is mandatory, we recommend recruitment procedures including hospital
      based rather than office-based physicians. However, physician characteristics
      were not associated with outcome.

PMID- 29166871
TI  - Contribution of diffusion-weighted imaging to conventional MRI for detection of
      haemorrhagic infarction in ovary torsion.
AB  - BACKGROUND: To assess the role of DWI in differentiation haemorrhagic ovary
      infarction from non-haemorrhagic one. METHODS: For this prospectively designed
      study, of 117 female patients who presented with acute lower quadrant pain and
      underwent MRI for suspicion of ovary torsion, results of only 29 patients (mean
      age, 24.7; SD, +/-5.7; age range, 18-37), with surgical and pathological
      confirmation of adnexal torsion, were included to the study. All patients
      underwent DWI after conventional MRI. Quantitative and qualitative analysis of
      both the torsed and contralateral normal ovary were performed. Results of
      conventional MRI and DWI were noted. RESULTS: At operation 15 patients were found
      to have haemorrhagic infarction while 14 had non-haemorrhagic infarction. Of the
      29 patients, 17 torsed ovaries could be salvaged in a viable state. We found
      statistically significant correlation of the ADC values, between haemorrhagic and
      non-haemorrhagic ovary infarction. The ADC values were significantly lower in
      patients with haemorrhagic infarction than non-haemorrhagic ones (p < 0.001).
      Using an ADC threshold of 1.27, the sensitivity of DWI for haemorrhagic
      infarction was 0.93 and specificity 0.85. CONCLUSION: DWI may be used with a
      significant success for the preoperative diagnosis of haemorrhagic infarction.
      This may be alerting for pre-emptive surgery in avoiding serious complications
      and preventing irreversible structural damage of the ovary.

PMID- 29166872
TI  - Experiences of adult patients using primary care services in Poland - a cross
      sectional study in QUALICOPC study framework.
AB  - BACKGROUND: Patients as real healthcare system users are important observers of
      primary care and are able to provide reliable information about the quality of
      care. The aim of this study was to explore the patients' experiences and their
      level of satisfaction with the process and outcomes of care provided by primary
      care physicians in Poland and to identify the characteristics of the patients,
      their physicians, and facilities associated with patient satisfaction. METHODS:
      The study is based on data from the Polish part of the Quality and Costs of
      Primary Care in Europe (QUALICOPC) cross-sectional, questionnaire-based study. In
      Poland, a nationally representative sample of 220 PC physicians and 1980 of their
      patients were recruited to take part in the study. As a study tool we used 3 out
      of 4 QUALICOPC questionnaires: "Patient Experience", "PC Physician" and
      "Fieldworker" questionnaires. RESULTS: The areas of the best quality perceived by
      Polish PC patients are: equity, accessibility of care and quality of service.
      Coordination and comprehensiveness of care are evaluated relatively worse. The
      patients' and their physicians' characteristics have a limited influence on
      patient satisfaction and experiences with Polish primary care. CONCLUSIONS:
      Primary health care in Poland is of good overall quality as perceived by the
      patients. Study participants were at most satisfied with accessibility and equity
      of care and less satisfied with coordination and comprehensiveness of care.
      Longer patient-doctor relationship and older age of patients were found as the
      most influential determinants of higher satisfaction. However, variables used in
      this study poorly explain the overall level of satisfaction. Further research is
      needed to identify the other determinants of patient satisfaction in the Polish
      population. Rural practices deserve additional attention due to highest
      proportions of both extremely satisfied and dissatisfied patients.

PMID- 29166873
TI  - Mortality patterns and risk among older men and women with intellectual
      disability: a Swedish national retrospective cohort study.
AB  - BACKGROUND: Sweden has closed all institutions and imposed legislation to ensure
      service and support for individuals with intellectual disability (ID).
      Understanding mortality among older individuals with ID is essential to inform
      development of health promotion and disease control strategies. We investigated
      patterns and risk of mortality among older adults with ID in Sweden. METHODS:
      This retrospective cohort study compared older adults aged 55 years and older
      with ID with a control population. Participants were followed during 2002-2015 or
      death, and censored if they moved out of Sweden. Individuals with ID were
      identified from two national registers: one covering all specialist health-care
      visits (out-patient visits and hospitalisation) and the other covering people
      accessing social/support services. Individuals with ID (n = 15,289) were matched
      with a control population by sex, birth year, and year of first
      hospitalisation/out-patient visit/access to LSS services. Cause-of-death data
      were recorded using International Classification of Diseases, Tenth Revision. Cox
      proportional hazards regression were conducted to assess if overall and cause
      specific mortality rate among individuals with ID was higher than in the Swedish
      population. RESULTS: The overall mortality rate among individuals with ID was
      2483 per 100,000 people compared with 810 in the control population. Among those
      who died, more individuals with ID were younger than 75 years and unmarried.
      Leading causes of death among individuals with ID were circulatory diseases
      (34%), respiratory diseases (17%) and neoplasms (15%). Leading causes of death in
      a sub-sample with Down syndrome (DS) were respiratory diseases (37%), circulatory
      diseases (26%) and mental/behavioural disorders (11%). Epilepsy and pneumonitis
      were more common among individuals with ID than controls. Alzheimer's disease was
      common in the control population and individuals with DS, but not among those
      with ID when DS was excluded. Individuals with ID had a higher overall mortality
      risk (hazard ratio [HR] 4.1, 95% confidence interval [CI] 4.0-4.3) and
      respiratory disease death risk (HR 12.5, 95% CI 10.9-14.2) than controls.
      CONCLUSION: Older adults with ID in Sweden carry a higher mortality risk compared
      with the general population, mainly attributable to respiratory, nervous and
      circulatory diseases. Care for this group, particularly during the terminal stage
      of illness, needs to be tailored based on understanding of their main health
      problem.

PMID- 29166874
TI  - Efficacy and safety of pertussis vaccination for pregnant women - a systematic
      review of randomised controlled trials and observational studies.
AB  - BACKGROUND: Worldwide, pertussis remains a major health problem among children.
      During the recent outbreaks of pertussis, maternal antenatal immunisation was
      introduced in several industrial countries. This systematic review aimed to
      synthesize evidence for the efficacy and safety of the pertussis vaccination that
      was given to pregnant women to protect infants from pertussis infection. METHODS:
      We searched literature in the Cochrane Central Register of Controlled Trials,
      Medline, Embase, and OpenGrey between inception of the various databases and 16
      May 2016. The search terms included 'pertussis', 'whooping cough', 'pertussis
      vaccine,' 'tetanus, diphtheria and pertussis vaccines' and 'pregnancy' and
      'perinatal'. RESULTS: We included 15 articles in this review, which represented
      12 study populations, involving a total of 203,835 mother-infant pairs from the
      US, the UK, Belgium, Israel, and Vietnam. Of the included studies, there were two
      randomised controlled trials (RCTs) and the rest were observational studies.
      Existing evidence suggests that vaccinations administered during 19-37 weeks of
      gestation are associated with significantly increased antibody levels in the
      blood of both mothers and their newborns at birth compared to placebo or no
      vaccination. However, there is a lack of robust evidence to suggest whether these
      increased antibodies can also reduce the incidence of pertussis (one RCT, n = 48,
      no incidence in either group) and pertussis-related severe complications (one
      observational study) or mortality (no study) in infants. Meanwhile, there is no
      evidence of increased risk of serious complications such as stillbirth (e.g. one
      RCT, n = 103, RR = 0, meaning no case in the vaccine group), or preterm birth
      (two RCTs, n = 151, RR = 0.86, 95%CI: 0.14-5.21) related to administration of the
      vaccine during pregnancy. CONCLUSION: Given that pertussis infection is
      increasing in many countries and that newborn babies are at greatest risk of
      developing severe complications from pertussis, maternal vaccination in the later
      stages of pregnancy should continue to be supported while further research should
      fill knowledge gaps and strengthen evidence of its efficacy and safety.

PMID- 29166875
TI  - Associations of childhood maltreatment with pre-pregnancy obesity and maternal
      postpartum mental health: a cross-sectional study.

PMID- 29166876
TI  - Gastroesophageal flap valve reflected EGJ morphology and correlated to acid
      reflux.
AB  - OBJECTIVE: The anatomy of esophagogastric junction (EGJ) serves as the anti
      reflux barrier. The gastroesophageal flap valve (GEFV) is a component of EGJ. The
      aim of the current study was to assess its correlation with the esophageal acid
      exposure and the impact on anti-reflux barrier function by using the metrics of
      EGJ contraction. METHODS: Eighty three patients with typical GERD symptoms were
      included in the study. Upper endoscopy, high-resolution manometry (HRM) and 24 h
      multichannel intraluminal impedance-pH (MII-pH) monitoring were performed in all
      patients. GEFV was determined as four grades during endoscopic examination based
      on the Hill classification. The esophageal pressure topography (EPT) metrics
      defined in the updated Chicago Classification were measured by HRM, including
      integrated relaxation pressure (IRP), EGJ contractile index (EGJ-CI),expiratory
      EGJ pressure(EGJP-exp) and inspiratory EGJ pressure (EGJP-insp). RESULTS: The
      GEFV grade III and IV was more commonly found in patients with esophagitits (p <
      0.05). The acid exposure time (AET%) and supine AET% were lower in patients with
      GEFV grade I (p < 0.01). There was weak correlation between AET% and GEFV grades
      (r = 0.27, p = 0.013). There were more EGJ morphology type III in patients with
      GEFV grade IV (p < 0.05).There were no significant differences on the values of
      four HRM metrics among the patients with different GEFV grades (p > 0.05).
      CONCLUSION: The GEFV grades were associated with acid reflux positively and could
      be a good reflection of EGJ morphology in HRM. But it had no impact on the four
      HRM metrics. Our research revealed that GEFV may play an assistant role in the
      anti-reflux barrier.

PMID- 29166877
TI  - A prospective study examining the role of myocardial Fibrosis in outcome
      following mitral valve repair IN DEgenerative mitral Regurgitation: rationale and
      design of the mitral FINDER study.
AB  - BACKGROUND: The optimal management of chronic severe primary degenerative mitral
      regurgitation (MR) is to repair the valve but identification of the optimal
      timing of surgery remains challenging. Current guidelines suggest 'watchful
      waiting' until the onset of symptoms or left ventricular (LV) dysfunction but
      these have been challenged as promoting 'rescue surgery'. Better predictors are
      required to inform decision-making in relation to the necessity and timing of
      surgery. Chronic volume overload is a stimulus for adverse adaptive LV
      remodelling. Subclinical reduction in LV strain before mitral repair predicts a
      fall in LV ejection fraction following surgery and is thought to reflect the
      development of myocardial fibrosis in response to chronic volume overload.
      Myocardial fibrosis can be detected non-invasively using cardiac magnetic
      resonance (CMR) imaging techniques as an expansion of the extracellular volume
      (ECV). METHODS/DESIGN: This study investigates whether: 1) patients with above
      median ECV will have smaller reduction in end-systolic volume index (as a measure
      of the degree of reverse LV remodelling) on CMR following mitral valve repair,
      compared to those with below median ECV; and 2) higher ECV on CMR, validated
      through histology, adversely impacts upon post-operative complications and
      symptomatic improvement following surgery. This is a multi-centre, prospective,
      cross-sectional comparison of patients prior to and 9 months following surgery
      for chronic severe primary degenerative MR. To establish the natural history of
      ECV in MR, an additional cohort of patients with asymptomatic MR who do not wish
      to consider early repair will be followed. Investigations include CMR,
      cardiopulmonary exercise test, stress echocardiography, signal-averaged
      electrocardiogram, 24-h electrocardiogram monitoring, laboratory tests and
      patient-reported outcome measures. Patients undergoing surgery will have cardiac
      biopsies performed at the time of mitral valve repair for histological
      quantification of fibrosis. DISCUSSION: This study will advance our understanding
      of ventricular remodelling in MR, its impact on patient symptoms and ventricular
      response following surgery. Establishing the link between myocardial fibrosis
      (measured on CMR and validated through histology), with early ventricular
      dysfunction, will offer physicians a novel non-invasive biomarker that can
      further inform the timing of surgery. TRIAL REGISTRATION: This trial was
      registered at ClinicalTrials.gov ( NCT02355418 ) on 30th November 2015.

PMID- 29166878
TI  - The ANDROMEDA prospective cohort study: predictive value of combined criteria to
      tailor breast cancer screening and new opportunities from circulating markers:
      study protocol.
AB  - BACKGROUND: In recent years growing interest has been posed on alternative ways
      to screen women for breast cancer involving different imaging techniques or
      adjusting screening interval by breast cancer risk estimates. A new research area
      is studying circulating microRNAs as molecular biomarkers potentially useful for
      non invasive early detection together with the analysis of single-nucleotide
      polymorphisms (SNPs). The Andromeda study is a prospective cohort study on women
      attending breast cancer screening in a northern Italian area. The aims of the
      study are: 1) to define appropriate women risk-based stratifications for
      personalized screening considering different factors (reproductive, family and
      biopsy history, breast density, lifestyle habits); 2) to evaluate the diagnostic
      accuracy of selected circulating microRNAs in a case-control study nested within
      the above mentioned cohort. METHODS: About 21,000 women aged 46-67 years
      compliant to screening mammography are expected to be enrolled. At enrolment,
      information on well-known breast cancer risk factors and life-styles habits are
      collected through self-admistered questionnaires. Information on breast density
      and anthropometric measurements (height, weight, body composition, and waist
      circumference) are recorded. In addition, women are requested to provide a blood
      sample for serum, plasma and buffy-coat storing for subsequent molecular analyses
      within the nested case-control study. This investigation will be performed on
      approximately 233 cases (screen-detected) and 699 matched controls to evaluate
      SNPs and circulating microRNAs. The whole study will last three years and the
      cohort will be followed up for ten years to observe the onset of new breast
      cancer cases. DISCUSSION: Nowadays women undergo the same screening protocol,
      independently of their breast density and their individual risk to develop breast
      cancer. New criteria to better stratify women in risk groups could enable the
      screening strategies to target high-risk women while reducing interventions in
      those at low-risk. In this frame the present study will contribute in identifying
      the feasibility and impact of implementing personalized breast cancer screening.
      TRIAL REGISTRATION: NCT02618538 (retrospectively registered on 27-11-2015.).

PMID- 29166879
TI  - A compendium of transcription factor and Transcriptionally active protein coding
      gene families in cowpea (Vigna unguiculata L.).
AB  - BACKGROUND: Cowpea (Vigna unguiculata (L.) Walp.) is the most important food and
      forage legume in the semi-arid tropics of sub-Saharan Africa where approximately
      80% of worldwide production takes place primarily on low-input, subsistence farm
      sites. Among the major goals of cowpea breeding and improvement programs are the
      rapid manipulation of agronomic traits for seed size and quality and improved
      resistance to abiotic and biotic stresses to enhance productivity. Knowing the
      suite of transcription factors (TFs) and transcriptionally active proteins (TAPs)
      that control various critical plant cellular processes would contribute
      tremendously to these improvement aims. RESULTS: We used a computational approach
      that employed three different predictive pipelines to data mine the cowpea genome
      and identified over 4400 genes representing 136 different TF and TAP families. We
      compare the information content of cowpea to two evolutionarily close species
      common bean (Phaseolus vulgaris), and soybean (Glycine max) to gauge the relative
      informational content. Our data indicate that correcting for genome size cowpea
      has fewer TF and TAP genes than common bean (4408 / 5291) and soybean (4408/
      11,065). Members of the GROWTH-REGULATING FACTOR (GRF) and Auxin/indole-3-acetic
      acid (Aux/IAA) gene families appear to be over-represented in the genome relative
      to common bean and soybean, whereas members of the MADS (Minichromosome
      maintenance deficient 1 (MCM1), AGAMOUS, DEFICIENS, and serum response factor
      (SRF)) and C2C2-YABBY appear to be under-represented. Analysis of the AP2-EREBP
      APETALA2-Ethylene Responsive Element Binding Protein (AP2-EREBP), NAC (NAM (no
      apical meristem), ATAF1, 2 (Arabidopsis transcription activation factor), CUC
      (cup-shaped cotyledon)), and WRKY families, known to be important in defense
      signaling, revealed changes and phylogenetic rearrangements relative to common
      bean and soybean that suggest these groups may have evolved different functions.
      CONCLUSIONS: The availability of detailed information on the coding capacity of
      the cowpea genome and in particular the various TF and TAP gene families will
      facilitate future comparative analysis and development of strategies for
      controlling growth, differentiation, and abiotic and biotic stress resistances of
      cowpea.

PMID- 29166880
TI  - Is the policy of allowing a female labor companion feasible in developing
      countries? Results from a cross sectional study among Sri Lankan practitioners.
AB  - BACKGROUND: Companionship during labor is known to have both physical and
      psychosocial benefits to mother and baby. Sri Lanka made a policy decision to
      allow a labour companion in 2011. However, implementation has been
      unsatisfactory. Given the leading role Obstetricians play in the implementation
      of policy, a study was undertaken to assess the knowledge, attitudes and
      practices among them. METHOD: A descriptive cross sectional study was conducted
      among consultant obstetricians working in the state hospitals using the platform
      'Survey Monkey'. RESULTS: Out of the 140 consultant obstetricians invited,
      68(48.5%) participated. Among the study participants, 40 (58.8%) did not allow
      labour companions in their wards. Lack of space (n = 32; 80%) and the volume of
      work in the labor wards (n = 22; 55%) were the commonest reasons for not allowing
      a companion. Only 16.7% (n = 5) of the obstetricians handling more than 300
      deliveries per month allowed a companion (p = 0.001). Less than 50% of the
      obstetricians were aware of the advantages associated with the practice such as
      shorter labor, lesser analgesic requirement, higher chances of a normal birth,
      improved neonatal outcome and reduced requirements for labor augmentation for
      slow progress of labor. Knowledge on advantages on breast feeding and reduced
      need of instrumental delivery also remained low. CONCLUSION: In an individual
      unit, the consultant often decides policy. The study points out the need to
      improve awareness among the practitioners.

PMID- 29166881
TI  - Mitochondrial pyruvate carrier 1 mediates abscisic acid-regulated stomatal
      closure and the drought response by affecting cellular pyruvate content in
      Arabidopsis thaliana.
AB  - BACKGROUND: Stomata are micropores surrounded by pairs of guard cells, and their
      opening is finely controlled to balance water vapor loss as transpiration and CO2
      absorption for photosynthesis. The regulatory signaling network for stomatal
      movement is complicated, and increasing numbers of new genes have been shown to
      be involved in this process. Our previous study indicated that a member of the
      plant putative mitochondrial pyruvate carrier (MPC) family, NRGA1, is a negative
      regulator of guard cell abscisic acid (ABA) signaling. In this study, we
      identified novel physiological roles of pyruvate and MPC1, another member of the
      MPC family, in the regulation of stomatal closure in Arabidopsis. RESULTS: Loss
      of-function mutants of MPC1 (mpc1) were hypersensitive to ABA-induced stomatal
      closure and ABA-activated guard cell slow-type anion currents, and showed a
      reduced rate of water loss upon drought treatment compared with wild-type plants.
      In contrast, plants overexpressing MPC1 showed a hyposensitive ABA response and
      increased sensitivity to drought stress. In addition, mpc1 mutants accumulated
      more pyruvate after drought or ABA treatment. The increased pyruvate content also
      induced stomatal closure and activated the slow-type anion channels of guard
      cells, and this process was dependent on the function of RbohD/F NADPH oxidases
      and reactive oxygen species concentrations in guard cells. CONCLUSIONS: Our
      findings revealed the essential roles of MPC1 and pyruvate in stomatal movement
      and plant drought resistance.

PMID- 29166882
TI  - Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of
      gastric cancer in West Bengal, India.
AB  - BACKGROUND: Gastric cancer (GC) is one of the most frequently diagnosed digestive
      tract cancers and carries a high risk of mortality. Acetaldehyde (AA), a
      carcinogenic intermediate of ethanol metabolism contributes to the risk of GC.
      The accumulation of AA largely depends on the activity of the major metabolic
      enzymes, alcohol dehydrogenase and aldehyde dehydrogenase encoded by the ADH
      (ADH1 gene cluster: ADH1A, ADH1B and ADH1C) and ALDH2 genes, respectively. This
      study aimed to evaluate the association between genetic variants in these genes
      and GC risk in West Bengal, India. METHODS: We enrolled 105 GC patients (cases),
      and their corresponding sex, age and ethnicity was matched to 108 normal
      individuals (controls). Genotyping for ADH1A (rs1230025), ADH1B (rs3811802,
      rs1229982, rs1229984, rs6413413, rs4147536, rs2066702 and rs17033), ADH1C (rs698)
      and ALDH2 (rs886205, rs968529, rs16941667 and rs671) was performed using DNA
      sequencing and RFLP. RESULTS: Genotype and allele frequency analysis of these
      SNPs revealed that G allele of rs17033 is a risk allele (A vs G: OR = 3.67, 95%
      CI = 1.54-8.75, p = 0.002) for GC. Significant association was also observed
      between rs671 and incidence of GC (p = 0.003). Moreover, smokers having the Lys
      allele of rs671 had a 7-fold increased risk of acquiring the disease (OR = 7.58,
      95% CI = 1.34-42.78, p = 0.009). CONCLUSION: In conclusion, rs17033 of ADH1B and
      rs671 of ALDH2 SNPs were associated with GC risk and smoking habit may further
      modify the effect of rs671. Conversely, rs4147536 of ADH1B might have a
      protective role in our study population. Additional studies with a larger patient
      population are needed to confirm our results.

PMID- 29166883
TI  - The humanistic burden of Pompe disease: are there still unmet needs? A systematic
      review.
AB  - BACKGROUND: Humanistic burden considers the impact of an illness on a patient's
      health-related quality of life (HRQoL), activities of daily living (ADL),
      caregiver health, and caregiver QoL. Humanistic burden also considers treatment
      satisfaction and adherence to treatment regimens. Pompe disease is an autosomal
      recessive, progressive, multisystemic neuromuscular disease. Approval of enzyme
      replacement therapy (ERT) markedly improved prognosis for patients, but
      considerable morbidity and a substantial humanistic burden remain. This article
      characterizes the humanistic burden of Pompe disease through a systematic
      literature review. METHODS: A systematic search of MEDLINE(r) and Embase(r) with
      back-referencing and supplementary literature searches was performed to retrieve
      data from interventional and non-interventional studies on the humanistic burden
      of Pompe disease. Publications were screened according to predefined criteria,
      extracted, and assessed for quality. Extracted data were narratively synthesized.
      RESULTS: No publications on the humanistic burden of infantile-onset Pompe
      disease (IOPD) were identified. As such, of 17 publications included here, all
      are in patients with late-onset Pompe disease (LOPD). Thirteen publications were
      initiated after approval of ERT, two were initiated before, and two overlapped
      the approval of ERT. The review shows that LOPD patients have a significantly
      lower HRQoL than the general population, even if treated with ERT. On
      transitioning to ERT, treatment was associated with improvement in the physical
      component score of the SF-36 and fatigue, although the SF-36 mental component
      score remained stable. Physical HRQoL remained below population norms after 4
      years of ERT. Significantly more ERT-treated patients reported pain than
      controls, and bodily pain worsened in later years following ERT initiation.
      Treatment-naive LOPD patients had significantly poorer ADL functioning compared
      with the general population, although ERT stabilized deteriorating functioning
      impairment. ERT studies showed caregivers provide 17.7 h/week informal care on
      average. Fifty percent, 40% and <20% of caregivers reported mental health,
      physical health, and financial/relational problems, respectively. In ERT-naive
      patients, wheelchair use and home ventilatory support was associated with lower
      physical HRQoL and ADL functioning. In ERT-treated patients, key factors
      predicting worse HRQoL and ADL functioning were higher respiratory distress,
      poorer sleep quality, greater pain, and more fatigue. CONCLUSIONS: Pompe disease
      has a substantial humanistic burden, with strong inter-relationships among and
      between humanistic burden parameters and clinical progression.

PMID- 29166884
TI  - Gray matter morphological anomalies in the cerebellar vermis in first-episode
      schizophrenia patients with cognitive deficits.
AB  - BACKGROUND: Cognitive deficits are a core feature of early schizophrenia.
      However, the pathological foundations underlying cognitive deficits are still
      unknown. The present study examined the association between gray matter density
      and cognitive deficits in first-episode schizophrenia. METHOD: Structural
      magnetic resonance imaging of the brain was performed in 34 first-episode
      schizophrenia patients and 21 healthy controls. Patients were divided into two
      subgroups according to working memory task performance. The three groups were
      well matched for age, gender, and education, and the two patient groups were also
      further matched for diagnosis, duration of illness, and antipsychotic treatment.
      Voxel-based morphometric analysis was performed to estimate changes in gray
      matter density in first-episode schizophrenia patients with cognitive deficits.
      The relationships between gray matter density and clinical outcomes were
      explored. RESULTS: Patients with cognitive deficits were found to have reduced
      gray matter density in the vermis and tonsil of cerebellum compared with patients
      without cognitive deficits and healthy controls, decreased gray matter density in
      left supplementary motor area, bilateral precentral gyrus compared with patients
      without cognitive deficits. Classifier results showed GMD in cerebellar vermis
      tonsil cluster could differentiate SZ-CD from controls, left supplementary motor
      area cluster could differentiate SZ-CD from SZ-NCD. Gray matter density values of
      the cerebellar vermis cluster in patients groups were positively correlated with
      cognitive severity. CONCLUSIONS: Decreased gray matter density in the vermis and
      tonsil of cerebellum may underlie early psychosis and serve as a candidate
      biomarker for schizophrenia with cognitive deficits.

PMID- 29166885
TI  - The impact of rheumatologist-performed ultrasound on diagnosis and management of
      inflammatory arthritis in routine clinical practice.
AB  - BACKGROUND: Rheumatologists increasingly perform ultrasound (US) imaging to aid
      diagnosis and management decisions. There is a need to determine the role of US
      in facilitating early diagnosis of inflammatory arthritis. This study describes
      the impact of US use by rheumatologists on diagnosis and management of
      inflammatory arthritis in routine UK clinical practice. METHODS: We conducted a
      prospective study in four secondary care rheumatology clinics, each with one
      consultant who routinely used US and one who did not. Consenting patients aged >
      18, newly referred with suspected inflammatory arthritis were included. Data were
      collected both retrospectively from medical records and via a prospectively
      completed physician questionnaire on US use. Analyses were stratified by US/non
      US groups and by sub-population of rheumatoid arthritis (RA)-diagnosed patients.
      RESULTS: 258 patients were included; 134 US and 124 non-US. 42% (56/134) of US
      and 47% (58/124) of non-US were diagnosed with RA. Results described for US and
      non-US cohorts, respectively as follows. The proportion of patients diagnosed at
      their first clinic visit was 37% vs 19% overall (p = 0.004) and 41% vs 19% in RA
      diagnosed patients (p = 0.01). The median time to diagnosis (months) was 0.85 vs
      2.00 (overall, p = 0.0046) and 0.23 vs 1.38 (RA-diagnosed, p = 0.0016). Median
      time (months) to initiation on a DMARD (where initiated) was 0.62 vs 1.41
      (overall, p = 0.0048) and 0.46 vs 1.81 (RA-diagnosed, p = 0.0007). CONCLUSION: In
      patients with suspected inflammatory arthritis, routine US use in newly referred
      patients seems to be associated with significantly earlier diagnosis and DMARD
      initiation.

PMID- 29166886
TI  - Trends in cardiovascular risk factors among U.S. men and women with and without
      diabetes, 1988-2014.
AB  - BACKGROUND: Studies evidenced that reduction in cardiovascular disease (CVD)
      mortality in diabetic patients can be attributed to improvements in major CVD
      risk factors and evidence-based treatments. Furthermore, studies showed that the
      relative risk of CVD mortality associated with diabetes compared with non
      diabetes is stronger in women than in men. Hence, we aimed to examine trends in
      CVD risk factors and intervention measures by sex and diabetic status. METHODS:
      Analysis of 5 distinct cross-sectional National Health and Nutrition Examination
      Surveys, 1988-1994, 1999-2002, 2003-2006, 2007-2010, and 2010-2014. Since
      detailed information on nontraditional risk factors such as sleep apnea was not
      available in each NHANES survey, traditional CVD risk factors including obesity,
      hypertension, and dyslipidemia were assessed in the study. To assess whether
      changes throughout the 27-year period differed by diabetes status, a logistic
      regression analysis was utilized to examine potential interaction effects between
      survey and diabetes. The similar process was repeated for sex. RESULTS: Means of
      all risk factors except body mass index and waist circumference decreased and the
      prevalence of antihypertensive and lipid-lowering medication use increased over
      time among diabetic and non-diabetic men and women. For both men and women,
      survey * diabetes status interaction terms for changes in HDL-cholesterol and
      triglyceride levels were not statistically significant, while the prevalence of
      antihypertensive and lipid-lowering medication use increased more in diabetic
      than in non-diabetic persons (all P < 0.001). For women, survey * diabetes status
      interaction terms indicated that compared with the first survey, total
      cholesterol, LDL-cholesterol, and non-HDL-cholesterol fallen more in diabetic
      than in non-diabetic persons (all P < 0.001). In the diabetic state, men
      experienced similar changes in means of all CVD risk factors and the prevalence
      of antihypertensive and lipid-lowering medication use as women (all P for
      interactions between survey and sex were >0.01). CONCLUSIONS: The major
      traditional CVD risk factors in diabetic men decreased to the same extent that
      they did for non-diabetic men. The magnitude of changes in the favorable trends
      in diabetic women was of similar or greater compared with those among non
      diabetic women. Diabetic women had as good an improvement in CVD risk factors as
      diabetic men.

PMID- 29166887
TI  - Self-confidence and knowledge of German ICU physicians in palliative care - a
      multicentre prospective study.
AB  - BACKGROUND: Little is known about ICU physicians' self-confidence and knowledge
      related to palliative care. Our objective was to investigate self-confidence and
      knowledge of German ICU physicians related to palliative care, and to assess the
      impact of work experience, gender, specialty and additional certifications in
      pain or palliative medicine. METHODS: In a multicentre prospective observational
      study ICU physicians of ten hospitals were asked to rate their self-confidence
      and to complete a multiple choice questionnaire for the assessment of knowledge.
      Beyond descriptive statistics and non-parametric tests for group comparisons,
      linear regression analysis was used to assess the impact of independent variable
      on self-confidence and knowledge. Spearman's rank test was calculated. RESULTS:
      55% of answers in the knowledge test were correct and more than half of the
      participants rated themselves as "rather confident" or "confident". Linear
      regression analysis revealed that an additional certificate in either pain or
      palliative medicine significantly increased both knowledge and self-confidence,
      but only 15 out of 137 participants had at least one of those certificates.
      Relation between self-confidence and the results of the knowledge test was weak
      (r = 0.270 in female) and very weak (r = -0.007 in male). CONCLUSIONS: Although
      the questionnaire needs improvement according to the item analysis, it appears
      that, with respect to palliative care, ICU Physicians' self-confidence is not
      related to their knowledge. An additional certificate in either pain or
      palliative medicine was positively correlated to both self-confidence and
      knowledge. However, only a minority of the participants were qualified through
      such a certificate.

PMID- 29166888
TI  - Cyclic stretch induced-retinal pigment epithelial cell apoptosis and cytokine
      changes.
AB  - BACKGROUND: The pathogenesis of age-related macular degeneration (AMD) is
      complex. It has been shown that vitreomacular traction (VMT) plays a role in the
      pathogenesis of AMD. We speculate that the continuous stretch induced by VMT
      might impair the function of retinal pigment epithelium (RPE) cells and it might
      also be involved in the progression of AMD. METHODS: Cultured ARPE-19 cells were
      subjected to cyclic stretch on the Flexcell Strain system at a level of 25%
      increment on the surface area for 8 h, 14 h, 20 h, 24 h. In another group, the
      stretch was withdrawn at 14 h and the cell cultured for another 6 h. Then, we
      observed the changes in morphology, apoptosis and expression of interleukin 6
      (IL6) and vascular endothelial growth factor (VEGF) in RPE cells under stretch.
      RESULTS: We found that stretch induced the RPE cells to change from a spreading
      shape into a rounded shape, and that the morphological changes were positively
      correlated with the duration of the stretch. The expression of pFAK397 and
      pRac1/cdc42 were elevated in a time-dependent fashion. The stretch resulted in an
      increase in the apoptosis ratio, with Bcl2, Bax and p53 also showing time
      dependent changes. In addition, up-regulation of IL6 and VEGF expression levels
      was also observed. After withdrawal of the stretch, all of these changes were
      significantly diminished. CONCLUSION: Stretch may induce morphological, cell
      apoptosis, and up-regulation of cytokines changes in RPE cells, indicating that
      cyclic stretching may participate in the progression of AMD by impeding the
      functions of the RPE.

PMID- 29166889
TI  - Overweight and obesity prevalence among Cree youth of Eeyou Istchee according to
      three body mass index classification systems.
AB  - BACKGROUND: Little is known about the suitability of three commonly used body
      mass index (BMI) classification systems for Indigenous youth. We estimated
      overweight and obesity prevalence among Cree youth of Eeyou Istchee according to
      three BMI classification systems, assessed the level of agreement between them,
      and evaluated their accuracy through body fat and cardiometabolic risk factors.
      METHODS: Data on 288 youth (aged 8-17 years) were collected. Overweight and
      obesity prevalence were estimated with Centers for Disease Control and Prevention
      (CDC), International Obesity Task Force (IOTF) and World Health Organization
      (WHO) criteria. Agreement was measured with weighted kappa (kappaw). Associations
      with body fat and cardiometabolic risk factors were evaluated by analysis of
      variance. RESULTS: Obesity prevalence was 42.7% with IOTF, 47.2% with CDC, and
      49.3% with WHO criteria. Agreement was almost perfect between IOTF and CDC
      (kappaw = 0.93), IOTF and WHO (kappaw = 0.91), and WHO and CDC (kappaw = 0.94).
      Means of body fat and cardiometabolic risk factors were significantly higher (P
      trend < 0.001) from normal weight to obesity, regardless of the system used.
      Youth considered overweight by IOTF but obese by CDC or WHO exhibited less severe
      clinical obesity. CONCLUSIONS: IOTF seems to be more accurate in identifying
      obesity in Cree youth.

PMID- 29166890
TI  - Continuous passive motion and physical therapy (CPM) versus physical therapy (PT)
      versus delayed physical therapy (DPT) after surgical release for elbow
      contractures; a study protocol for a prospective randomized controlled trial.
AB  - BACKGROUND: The elbow is prone to stiffness after trauma. To regain functional
      elbow motion several conservative- and surgical treatment options are available.
      Conservative treatment includes physical therapy, intra-articular injections with
      corticosteroids and a static progressive or dynamic splinting program. If
      conservative treatment fails, an operative release of the posttraumatic stiff
      elbow is often performed. The best Evidence-Based rehabilitation protocol for
      patients after an operative release is unknown to date and differs per surgeon,
      hospital and country. Options include early- or delayed motion supervised by a
      physical therapist, immediate continuous passive motion (CPM), (night) splinting
      and a static progressive or dynamic splinting program. METHODS/DESIGN: The SET
      Study (Stiff Elbow Trial) is a single-centre, prospective, randomized controlled
      trial. The primary objective of this study is to compare the active Range of
      Motion (ROM) (flexion arc and rotational arc) twelve months after surgery between
      three groups. The first group will receive in-hospital CPM in combination with
      early motion Physical Therapy (PT) supervised by a physical therapist, the second
      group will receive only in-hospital early motion PT supervised by a physical
      therapist and the third group will receive outpatient supervised PT from
      postoperative day seven till ten. Secondary outcome measures will be Patient
      Reported Outcome Measures (PROMs) including the Mayo Elbow Performance Score
      (MEPS), the Oxford Elbow Score (OES), the quick Disabilities of Arm, Shoulder and
      Hand (qDASH) score, Visual Analogue pain Scale in rest and activity (VAS), Pain
      Catastrophizing Scale (PCS), the Short Form (SF)-36, the Centre for
      Epidemiological Studies Depression Scale Revised (CESD-R) and the Work
      Rehabilitation Questionnaire (WORQ) for the upper limb. DISCUSSION: A successful
      completion of this trial will provide evidence on the best rehabilitation
      protocol in order to (re)gain optimal motion after surgical release of the stiff
      elbow. TRIAL REGISTRATION: The trial is registered at the Dutch Trial Register:
      NTR6067 , 31-8-2016.

PMID- 29166891
TI  - Pediatric hospital admissions in Indigenous children: a population-based study in
      remote Australia.
AB  - BACKGROUND: We analysed hospital admissions of a predominantly Aboriginal cohort
      of children in the remote Fitzroy Valley in Western Australia during the first 7
      years of life. METHODS: All children born between January 1, 2002 and December
      31, 2003 and living in the Fitzroy Valley in 2009-2010 were eligible to
      participate in the Lililwan Project. Of 134 eligible children, 127 (95%)
      completed Stage 1 (interviews of caregivers and medical record review) in 2011
      and comprised our cohort. Lifetime (0-7 years) hospital admission data were
      available and included the dates, and reasons for admission, and comorbidities.
      Conditions were coded using ICD-10-AM discharge codes. RESULTS: Of the 127
      children, 95.3% were Indigenous and 52.8% male. There were 314 admissions for 424
      conditions in 89 (70.0%) of 127 children. The 89 children admitted had a median
      of five admissions (range 1-12). Hospitalization rates were similar for both
      genders (p = 0.4). Of the admissions, 108 (38.6%) were for 56 infants aged <12
      months (median = 2.5, range = 1-8). Twelve of these admissions were in neonates
      (aged 0-28 days). Primary reasons for admission (0-7 years) were infections of
      the lower respiratory tract (27.4%), gastrointestinal system (22.7%), and upper
      respiratory tract (11.4%), injury (7.0%), and failure to thrive (5.4%).
      Comorbidities, particularly upper respiratory tract infections (18.1%), failure
      to thrive (13.6%), and anaemia (12.7%), were common. In infancy, primary cause
      for admission were infections of the lower respiratory tract (40.8%),
      gastrointestinal (25.9%) and upper respiratory tract (9.3%). Comorbidities
      included upper respiratory tract infections (33.3%), failure to thrive (18.5%)
      and anaemia (18.5%). CONCLUSION: In the Fitzroy Valley 70.0% of children were
      hospitalised at least once before age 7 years and over one third of admissions
      were in infants. Infections were the most common reason for admission in all age
      groups but comorbidities were common and may contribute to need for admission.
      Many hospitalizations were feasibly preventable. High admission rates reflect
      disadvantage, remote location and limited access to primary healthcare and
      outpatient services. Ongoing public health prevention initiatives including
      breast feeding, vaccination, healthy diet, hygiene and housing improvements are
      crucial, as is training of Aboriginal Health Workers to increase services in
      remote communities.

PMID- 29166892
TI  - In vitro cytotoxic activity of medicinal plants from Nigeria ethnomedicine on
      Rhabdomyosarcoma cancer cell line and HPLC analysis of active extracts.
AB  - BACKGROUND: Cancer is a leading cause of death world-wide, with approximately
      17.5 million new cases and 8.7 million cancer related deaths in 2015. The
      problems of poor selectivity and severe side effects of the available anticancer
      drugs, have demanded the need for the development of safer and more effective
      chemotherapeutic agents. The present study was aimed at determining the
      cytotoxicities of 31 medicinal plants extracts, used in Nigerian ethnomedicine
      for the treatment of cancer. METHODS: The plant extracts were screened for
      cytotoxicity, using the brine shrimp lethality assay (BSLA) and MTT cytotoxicity
      assay. Rhabdomyosarcoma (RD) cell line, normal Vero cell line and the normal
      prostate (PNT2) cell line were used for the MTT assay, while Artemia salina
      nauplii was used for the BSLA. The phytochemical composition of the active plant
      extracts was determined by high performance liquid chromatography (HPLC)
      analysis. RESULTS: The extract of Eluesine indica (L.) Gaertn (Poaceae), with a
      LC50 value of 76.3 MUg/mL, had the highest cytotoxicity on the brine shrimp
      larvae compared to cyclophosphamide (LC50 = 101.3 MUg/mL). Two plants extracts,
      Macaranga barteri Mull. Arg. (Euphorbiaceae) and Calliandra portoricensis (Jacq.)
      Benth (Leguminosae) exhibited significant cytotoxic activity against the RD cell
      line and had comparable lethal activity on the brine shrimps. Further cytotoxic
      investigation showed that the dichloromethane fraction of Macaranga barteri (DMB)
      and the ethyl acetate fraction of Calliandra portoricensis (ECP), exhibited
      approximately 6-fold and 4-fold activity, respectively, compared to
      cyclophosphamide on RD cell line. Determination of selective index (SI) using
      Vero and PNT2 cell line indicated that DMB and ECP displayed a high degree of
      selectivity against the cancer cell under investigation. HPLC analysis showed
      that 3,5dicaffeoylquinic acid, acteoside, kampferol-7-O-glucoside and bastadin 11
      were the major components of DMB while the major components of ECP were
      neurolenin B, nigrosporolide and trans-geranic acid. CONCLUSION: The results
      demonstrate the cytotoxicity of Macaranga barteri and Calliandra portoricensis
      extracts, which are used in Nigerian folklore for cancer treatment.

PMID- 29166893
TI  - The effectiveness of interventions aimed at increasing physical activity in
      adults with persistent musculoskeletal pain: a systematic review and meta
      analysis.
AB  - BACKGROUND: Individuals with persistent musculoskeletal pain (PMP) have an
      increased risk of developing co-morbid health conditions and for early-mortality
      compared to those without pain. Despite irrefutable evidence supporting the role
      of physical activity in reducing these risks; there has been limited synthesis of
      the evidence, potentially impacting the optimisation of these forms of
      interventions. This review examines the effectiveness of interventions in
      improving levels of physical activity and the components of these interventions.
      METHODS: Randomised and quasi-randomised controlled trials were included in this
      review. The following databases were searched from inception to March 2016:
      CENTRAL in the Cochrane Library, Cochrane Database of Systematic Reviews (CDSR),
      MEDLINE, Embase, CINAHL, PsycINFO and AMED. Two reviewers independently screened
      citations, assessed eligibility, extracted data, assessed risk of bias and coded
      intervention content using the behaviour change taxonomy (BCTTv1) of 93
      hierarchically clustered techniques. GRADE was used to rate the quality of the
      evidence. RESULTS: The full text of 276 articles were assessed for eligibility,
      twenty studies involving 3441 participants were included in the review. Across
      the studies the mean number of BCTs coded was eight (range 0-16); with 'goal
      setting' and 'instruction on how to perform the behaviour' most frequently coded.
      For measures of subjective physical activity: interventions were ineffective in
      the short term, based on very low quality evidence; had a small effect in the
      medium term based on low quality evidence (SMD 0.25, 95% CI 0.01 to 0.48) and had
      a small effect in the longer term (SMD 0.21 95% CI 0.08 to 0.33) based on
      moderate quality evidence. For measures of objective physical activity:
      interventions were ineffective - based on very low to low quality evidence.
      CONCLUSIONS: There is some evidence supporting the effectiveness of interventions
      in improving subjectively measured physical activity however, the evidence is
      mostly based on low quality studies and the effects are small. Given the quality
      of the evidence, further research is likely/very likely to have an important
      impact on our confidence in effect estimates and is likely to change the
      estimates. Future studies should provide details on intervention components and
      incorporate objective measures of physical activity.

PMID- 29166894
TI  - How do public health professionals view and engage with research? A qualitative
      interview study and stakeholder workshop engaging public health professionals and
      researchers.
AB  - BACKGROUND: With increasing financial pressures on public health in England, the
      need for evidence of high relevance to policy is now stronger than ever. However,
      the ways in which public health professionals (PHPs) and researchers relate to
      one another are not necessarily conducive to effective knowledge translation.
      This study explores the perspectives of PHPs and researchers when interacting,
      with a view to identifying barriers to and opportunities for developing practice
      that is effectively informed by research. METHODS: This research focused on
      examples from two responsive research schemes, which provide university-based
      support for research-related enquiries from PHPs: the NIHR SPHR Public Health
      Practitioner Evaluation Scheme1 and the responsive research service AskFuse2. We
      examined enquiries that were submitted to both between 2013 and 2015, and
      purposively selected eight enquiries for further investigation by interviewing
      the PHPs and researchers involved in these requests. We also identified
      individuals who were eligible to make requests to the schemes but chose not to do
      so. In-depth interviews were conducted with six people in relation to the PHPES
      scheme, and 12 in relation to AskFuse. The interviews were transcribed and
      analysed using thematic framework analysis. Verification and extension of the
      findings were sought in a stakeholder workshop. RESULTS: PHPs recognised the
      importance of research findings for informing their practice. However, they
      identified three main barriers when trying to engage with researchers: 1)
      differences in timescales; 2) limited budgets; and 3) difficulties in identifying
      appropriate researchers. The two responsive schemes addressed some of these
      barriers, particularly finding the right researchers to work with and securing
      funding for local evaluations. The schemes also supported the development of new
      types of evidence. However, other barriers remained, such as differences in
      timescales and the resources needed to scale-up research. CONCLUSIONS: An
      increased mutual awareness of the structures and challenges under which PHPs and
      researchers work is required. Opportunities for frequent and meaningful
      engagement between PHPs and researchers can help to overcome additional barriers
      to co-production of evidence. Collaborative models, such as the use of
      researchers embedded in practice might facilitate this; however, flexible
      research funding schemes are needed to support these models.

PMID- 29166895
TI  - Retrospective data on causes of childhood vision impairment in Eritrea.
AB  - BACKGROUND: Proper information on causes of childhood vision loss is essential in
      developing appropriate strategies and programs to address such causes. This study
      aimed at identifying the causes of vision loss in children attending the national
      referral eye hospital with the only pediatric ophthalmology service in Eritrea.
      METHODS: A retrospective data review was conducted for all the children (< 16
      years of age) who attended Berhan Aiyni National Referral Eye Hospital in five
      years period from January 2011 to December 2015. Causes of vision loss for
      children with vision impairment (recorded visual acuity less than 6/18 for
      distance in the better eye) was classified by the anatomical site affected and by
      underlying etiology based on the timing of the insult and causal factor. RESULTS:
      The medical record cards of 22,509 children were reviewed, of whom 249 (1.1%)
      were visually impaired. The mean age of the participants was 7.82 +/- 5.43 years
      (range: one month to 16 years) and male to female ratio was 1:0.65. The leading
      causes of vision loss were cataract (19.7%), corneal scars (15.7%), refractive
      error and amblyopia (12.1%), optic atrophy (6.4%), phthisis bulbi (6.4%), aphakia
      (5.6%) and glaucoma (5.2%). Childhood factors including trauma were the leading
      causes identified (34.5%) whereas other causes included hereditary factors (4%),
      intrauterine factors (2.0%) and perinatal factors (4.4%). In 55.0% of the
      children, the underlying etiology could not be attributed. Over two-thirds
      (69.9%) of vision loss was potentially avoidable in nature. CONCLUSION: This
      study explored the causes of vision loss in Eritrean children using hospital
      based data. Cataract corneal opacities, refractive error and amblyopia, globe
      damage due to trauma, infection and nutritional deficiency, retinal disorders,
      and other congenital abnormalities were the leading causes of childhood vision
      impairment in children attending the tertiary eye hospital in Eritrea. As
      majority of the causes of vision loss was due to avoidable causes, we recommended
      primary level public health strategies to prevent ocular injuries, vitamin A
      deficiency, perinatal infections and retinopathy of prematurity as well as
      specialist pediatric eye care facilities for cataract, refractive errors,
      glaucoma and rehabilitative services to address childhood vision loss in Eritrea.

PMID- 29166896
TI  - Graph-theoretical comparison of normal and tumor networks in identifying BRCA
      genes.
AB  - BACKGROUND: Identification of driver genes related to certain types of cancer is
      an important research topic. Several systems biology approaches have been
      suggested, in particular for the identification of breast cancer (BRCA) related
      genes. Such approaches usually rely on differential gene expression and/or
      mutational landscape data. In some cases interaction network data is also
      integrated to identify cancer-related modules computationally. RESULTS: We
      provide a framework for the comparative graph-theoretical analysis of networks
      integrating the relevant gene expression, mutations, and potein-protein
      interaction network data. The comparisons involve a graph-theoretical analysis of
      normal and tumor network pairs across all instances of a given set of breast
      cancer samples. The network measures under consideration are based on appropriate
      formulations of various centrality measures: betweenness, clustering
      coefficients, degree centrality, random walk distances, graph-theoretical
      distances, and Jaccard index centrality. CONCLUSIONS: Among all the studied
      centrality-based graph-theoretical properties, we show that a betweenness-based
      measure differentiates BRCA genes across all normal versus tumor network pairs,
      than the rest of the popular centrality-based measures. The AUROC and AUPR values
      of the gene lists ordered with respect to the measures under study as compared to
      NCBI BioSystems pathway and the COSMIC database of cancer genes are the largest
      with the betweenness-based differentiation, followed by the measure based on
      degree centrality. In order to test the robustness of the suggested measures in
      prioritizing cancer genes, we further tested the two most promising measures,
      those based on betweenness and degree centralities, on randomly rewired networks.
      We show that both measures are quite resilient to noise in the input interaction
      network. We also compared the same measures against a state-of-the-art
      alternative disease gene prioritization method, MUFFFINN. We show that both our
      graph-theoretical measures outperform MUFFINN prioritizations in terms of ROC and
      precions/recall analysis. Finally, we filter the ordered list of the best
      measure, the betweenness-based differentiation, via a maximum-weight independent
      set formulation and investigate the top 50 genes in regards to literature
      verification. We show that almost all genes in the list are verified by the
      breast cancer literature and three genes are presented as novel genes that may
      potentialy be BRCA-related but missing in literature.

PMID- 29166897
TI  - Do effects of common case-mix adjusters on patient experiences vary across
      patient groups?
AB  - BACKGROUND: Many survey studies in health care adjust for demographic
      characteristics such as age, gender, educational attainment and general health
      when performing statistical analyses. Whether the effects of these demographic
      characteristics are consistent between patient groups remains to be determined.
      This is important as the rationale for adjustment is often that demographic sub
      groups differ in their so-called 'response tendency'. This rationale may be less
      convincing if the effects of response tendencies vary across patient groups. The
      present paper examines whether the impact of these characteristics on patients'
      global rating of care varies across patient groups. METHODS: Secondary analyses
      using multi-level regression models were performed on a dataset including 32
      different patient groups and 145,578 observations. For each demographic variable,
      the 95% expected range of case-mix coefficients across patient groups is
      presented. In addition, we report whether the variance of coefficients for
      demographic variables across patient groups is significant. RESULTS: Overall,
      men, elderly, lower educated people and people in good health tend to give higher
      global ratings. However, these effects varied significantly across patient groups
      and included the possibility of no effect or an opposite effect in some patient
      groups. CONCLUSION: The response tendency attributed to demographic
      characteristics - such as older respondents being milder, or higher educated
      respondents being more critical - is not general or universal. As such, the
      mechanism linking demographic characteristics to survey results on patient
      experiences with quality of care is more complicated than a general response
      tendency. It is possible that the response tendency interacts with patient group,
      but it is also possible that other mechanisms are at play.

PMID- 29166898
TI  - Stakeholders perspectives on the key components of community-based interventions
      coordinating care in dementia: a qualitative systematic review.
AB  - BACKGROUND: Interventions aiming to coordinate services for the community-based
      dementia population vary in components, organisation and implementation. In this
      review we aimed to investigate the views of stakeholders on the key components of
      community-based interventions coordinating care in dementia. METHODS: We searched
      four databases from inception to June 2015; Medline, The Cochrane Library, EMBASE
      and PsycINFO, this was aided by a search of four grey literature databases, and
      backward and forward citation tracking of included papers. Title and abstract
      screening was followed by a full text screen by two independent reviewers, and
      quality was assessed using the CASP appraisal tool. We then conducted thematic
      synthesis on extracted data. RESULTS: A total of seven papers from five
      independent studies were included in the review, and encompassed the views of
      over 100 participants from three countries. Through thematic synthesis we
      identified 32 initial codes that were grouped into 5 second-order themes: (1)
      case manager had four associated codes and described preferences for the case
      manager personal and professional attributes, including a sound knowledge in
      dementia and availability of local services; (2) communication had five
      associated codes and emphasized the importance stakeholders placed on
      multichannel communication with service users, as well as between
      multidisciplinary teams and across organisations; (3) intervention had 11
      associated codes which focused primarily on the practicalities of implementation
      such as the contact type and frequency between case managers and service users,
      and the importance of case manager training and service evaluation; (4) resources
      had five associated codes which outlined stakeholder views on the required
      resources for coordinating interventions and potential overlap with existing
      resources, as well as arising issues when available resources do not meet those
      required for successful implementation; and (5) support had seven associated
      codes that reflect the importance that was placed on the support network around
      the case manager and the investment of professionals involved directly in care as
      well as the wider professional network. CONCLUSION: The synthesis of relevant
      qualitative studies has shown how various stakeholder groups considered dementia
      care coordination interventions to be acceptable, useful and appropriate for
      dementia care, and have clear preferences for components, implementation methods
      and settings of these interventions. By incorporating stakeholders' perspectives
      and preferences when planning and developing coordinating interventions we may
      increase the likelihood of successful implementation and patient benefits.

PMID- 29166899
TI  - Medical thoracoscopy for exudative pleural effusion: an eight-year experience
      from a country with a young population.
AB  - BACKGROUND: With the exception of areas with high prevalence of tuberculosis,
      medical thoracoscopy is becoming the diagnostic modality of choice for exudative
      pleural effusions. The aims of this study were to determine the diagnostic yield
      and safety of medical thoracoscopy for exudative pleural effusions and ascertain
      the etiology of such effusions in Qatar. METHODS: This is a retrospective
      descriptive study of 407 patients who underwent diagnostic medical thoracoscopy
      for exudative pleural effusions from January, 2008 till December, 2015 at the
      only tertiary referral center performing this procedure in Qatar. RESULTS:
      Tuberculosis was the most common etiology of exudative pleural effusions in Qatar
      accounting for 84.5% of all causes. Around 85% of patients were young males (mean
      age of 33 +/- 12.1 years). The diagnostic yield of medical thoracoscopy for
      tuberculous pleural effusion was 91.4%. Malignant pleural effusions accounted for
      5.2% of cases. Minor bleeding occurred in 1.2% of cases with no procedure-related
      mortality observed. CONCLUSION: Medical thoracoscopy is a very safe procedure.
      Tuberculous pleuritis is by far the most common etiology of exudative pleural
      effusions in Qatar. Closed needle biopsy is a worth consideration as an initial
      safe, easy and low-cost diagnostic modality for exudative pleural effusions in
      this country.

PMID- 29166900
TI  - Association between borderline dysnatremia and mortality insight into a new data
      mining approach.
AB  - BACKGROUND: Even small variations of serum sodium concentration may be associated
      with mortality. Our objective was to confirm the impact of borderline dysnatremia
      for patients admitted to hospital on in-hospital mortality using real life care
      data from our electronic health record (EHR) and a phenome-wide association
      analysis (PheWAS). METHODS: Retrospective observational study based on patient
      data admitted to Hopital Europeen George Pompidou, between 01/01/2008 and
      31/06/2014; including 45,834 patients with serum sodium determinations on
      admission. We analyzed the association between dysnatremia and in-hospital
      mortality, using a multivariate logistic regression model to adjust for classical
      potential confounders. We performed a PheWAS to identify new potential
      confounders. RESULTS: Hyponatremia and hypernatremia were recorded for 12.0% and
      1.0% of hospital stays, respectively. Adjusted odds ratios (ORa) for severe,
      moderate and borderline hyponatremia were 3.44 (95% CI, 2.41-4.86), 2.48 (95% CI,
      1.96-3.13) and 1.98 (95% CI, 1.73-2.28), respectively. ORa for severe, moderate
      and borderline hypernatremia were 4.07 (95% CI, 2.92-5.62), 4.42 (95% CI, 2.04
      9.20) and 3.72 (95% CI, 1.53-8.45), respectively. Borderline hyponatremia (ORa =
      1.57 95% CI, 1.35-1.81) and borderline hypernatremia (ORa = 3.47 95% CI, 2.43
      4.90) were still associated with in-hospital mortality after adjustment for
      classical and new confounding factors identified through the PheWAS analysis.
      CONCLUSION: Borderline dysnatremia on admission are independently associated with
      a higher risk of in-hospital mortality. By using medical data automatically
      collected in EHR and a new data mining approach, we identified new potential
      confounding factors that were highly associated with both mortality and
      dysnatremia.

PMID- 29166901
TI  - Tracking dyspnea up to supplemental oxygen prescription among patients with
      pulmonary fibrosis.
AB  - BACKGROUND: Dyspnea is the hallmark symptom of pulmonary fibrosis. Supplemental
      oxygen (O2) is prescribed to many patients with pulmonary fibrosis in hopes of
      alleviating dyspnea and improving physical functioning. We used response data
      from the University of California San Diego Shortness of Breath Questionnaire
      (UCSD) which was administered monthly in the context of a longitudinal,
      observational study to plot a rich trajectory for dyspnea over time in patients
      with pulmonary fibrosis. We used other data from that study to identify clinical
      predictors of being prescribed O2 and to provide additional information for how
      UCSD scores could be used for clinical purposes. METHODS: We used linear mixed
      effects models and multivariate Cox proportional hazards to model change in
      dyspnea scores over time and to identify significant predictors of time-to-O2
      prescription among a pool of clinically-meaningful candidate variables. In the
      longitudinal study, all decisions, including whether or not to prescribe O2, were
      made by subjects' treating physicians, not members of the research team. RESULTS:
      One-hundred ninety-four subjects with pulmonary fibrosis completed more than one
      UCSD or were prescribed O2 at some point during the follow-up period (N = 43).
      Twenty-eight of the 43 had analyzable, longitudinal data and contribute data to
      the longitudinal UCSD analyses. All 43 were included in the time-to-O2
      prescription analyses. Subjects prescribed O2 had more severe dyspnea at
      enrollment (38.4 +/- 19.6 vs. 22.6 +/- 18.7, p < 0.0001) and a steeper increase
      in UCSD scores over time (slope = 1.18 +/- 0.53 vs. 0.24 +/- 0.09 points per
      month, p = 0.02) than subjects not prescribed O2. Controlling for baseline UCSD
      score and FVC%, subjects with a clinical summary diagnosis of idiopathic
      pulmonary fibrosis (IPF) were far more likely to be prescribed O2 than subjects
      with other forms of pulmonary fibrosis (hazard ratio = 4.85, (2.19, 10.74), p <
      0.0001). CONCLUSIONS: Baseline dyspnea and rise in dyspnea over time predict
      timing of O2 prescription. Accounting for disease severity, patients with IPF are
      more likely than patients with other forms of pulmonary fibrosis to be prescribed
      O2. UCSD scores provide clinically useful information; frequent administration
      could yield timely data on changes in disease status in patients with pulmonary
      fibrosis. TRIAL REGISTRATION: The longitudinal study is registered on
      ClinicalTrials.gov ( NCT01961362 ). Registered October 9, 2013.

PMID- 29166902
TI  - A national stakeholder consensus study of challenges and priorities for clinical
      learning environments in postgraduate medical education.
AB  - BACKGROUND: High quality clinical learning environments (CLE) are critical to
      postgraduate medical education (PGME). The understaffed and overcrowded
      environments in which many residents work present a significant challenge to
      learning. The purpose of this study was to develop a national expert group
      consensus amongst stakeholders in PGME to; (i) identify important barriers and
      facilitators of learning in CLEs and (ii) indicate priority areas for
      improvement. Our objective was to provide information to focus efforts to provide
      high quality CLEs. METHODS: Group Concept Mapping (GCM) is an integrated mixed
      methods approach to generating expert group consensus. A multi-disciplinary group
      of experts were invited to participate in the GCM process via an online platform.
      Multi-dimensional scaling and hierarchical cluster analysis were used to analyse
      participant inputs in regard to barriers, facilitators and priorities. RESULTS:
      Participants identified facilitators and barriers in ten domains within clinical
      learning environments. Domains rated most important were those which related to
      residents' connection to and engagement with more senior doctors. Organisation
      and conditions of work and Time to learn with senior doctors during patient care
      were rated as the most difficult areas in which to make improvements.
      CONCLUSIONS: High quality PGME requires that residents engage and connect with
      senior doctors during patient care, and that they are valued and supported both
      as learners and service providers. Academic medicine and health service managers
      must work together to protect these elements of CLEs, which not only shape
      learning, but impact quality of care and patient safety.

PMID- 29166903
TI  - Evaluation of microRNA expression in plasma and skeletal muscle of thoroughbred
      racehorses in training.
AB  - BACKGROUND: Circulating miRNAs (ci-miRNAs) are endogenous, non-coding RNAs
      emerging as potential diagnostic biomarkers. Equine miRNAs have been previously
      identified including subsets of tissue-specific miRNAs. In order to investigate
      ci-miRNAs as diagnostic tools, normal patterns of expression for different
      scenarios including responses to exercise need to be identified. Human studies
      have demonstrated that many ci-miRNAs are up-regulated following exercise with
      changes in expression patterns in skeletal muscle. However, technical challenges
      such as haemolysis impact on accurate plasma ci-miRNA quantification, with
      haemolysis often occurring naturally in horses following moderate-to-intense
      exercise. The objectives of this study were to identify plasma ci-miRNA profiles
      and skeletal muscle miRNAs before and after exercise in Thoroughbreds (Tb), and
      to evaluate for the presence and effect of haemolysis on plasma ci-miRNA
      determination. Resting and post-exercise plasma ci-miRNA profiles and haemolysis
      were evaluated in twenty 3 year-old Tbs in sprint training. Resting and post
      exercise skeletal muscle miRNA abundance was evaluated in a second cohort of
      eleven 2 year-old Tbs just entering sprint training. Haemolysis was further
      quantified in resting blood samples from twelve Tbs in sprint training. A human
      plasma panel containing 179 miRNAs was used for profiling, with haemolysis
      assessed spectrophotometrically. Data was analysed using a paired Student's t
      test and Pearson's rank correlation. RESULTS: Plasma ci-miRNA data for 13/20
      horses and all skeletal muscle miRNA data passed quality control. From plasma,
      52/179 miRNAs were detected at both time-points. Haemolysis levels were greater
      than the threshold for accurate quantification of ci-miRNAs in 18/25 resting and
      all post-exercise plasma samples. Positive correlations (P < 0.05) between
      haemolysis and miRNA abundance were detected for all but 4 miRNAs, so exercise
      induced changes in plasma ci-miRNA expression could not be quantified. In
      skeletal muscle samples, 97/179 miRNAs were detected with 5 miRNAs (miR-21-5p,
      let-7d-3p, let-7d-5p, miR-30b-5p, miR-30e-5p) differentially expressed (DE, P <
      0.05) between time-points. CONCLUSIONS: The degree of haemolysis needs to be
      determined prior to quantifying plasma ci-miRNA expression from horses in high
      intensity exercise training. Identification of DE miRNAs in skeletal muscle
      indicates modification of miRNA expression may contribute to adaptive training
      responses in Tbs. Using a human plasma panel likely limited detection of equine
      specific miRNAs.

PMID- 29166904
TI  - Behaviors in Advance Care Planning and ACtions Survey (BACPACS): development and
      validation part 1.
AB  - BACKGROUND: Although advance care planning (ACP) is fairly well understood,
      significant barriers to patient participation remain. As a result, tools to
      assess patient behaviour are required. The objective of this study was to improve
      the measurement of patient engagement in ACP by detecting existing survey design
      issues and establishing content and response process validity for a new survey
      entitled Behaviours in Advance Care Planning and ACtions Survey (BACPACS).
      METHODS: We based our new tool on that of an existing ACP engagement survey.
      Initial item reduction was carried out using behavior change theories by content
      and design experts to help reduce response burden and clarify questions. Thirty
      two patients with chronic diseases (cancer, heart failure or renal failure) were
      recruited for the think aloud cognitive interviewing with the new, shortened
      survey evaluating patient engagement with ACP. Of these, n = 27 had data eligible
      for analysis (n = 8 in round 1 and n = 19 in rounds 2 and 3). Interviews were
      audio-recorded and analyzed using the constant comparison method. Three reviewers
      independently listened to the interviews, summarized findings and discussed
      discrepancies until consensus was achieved. RESULTS: Item reduction from key
      content expert review and conversation analysis helped decrease number of items
      from 116 in the original ACP Engagement Survey to 24-38 in the new BACPACS
      depending on branching of responses. For the think aloud study, three rounds of
      interviews were needed until saturation for patient clarity was achieved. The
      understanding of ACP as a construct, survey response options, instructions and
      terminology pertaining to patient engagement in ACP warranted further
      clarification. CONCLUSIONS: Conversation analysis, content expert review and
      think aloud cognitive interviewing were useful in refining the new survey
      instrument entitled BACPACS. We found evidence for both content and response
      process validity for this new tool.

PMID- 29166905
TI  - Barriers to data quality resulting from the process of coding health information
      to administrative data: a qualitative study.
AB  - BACKGROUND: Administrative health data are increasingly used for research and
      surveillance to inform decision-making because of its large sample sizes,
      geographic coverage, comprehensivity, and possibility for longitudinal follow-up.
      Within Canadian provinces, individuals are assigned unique personal health
      numbers that allow for linkage of administrative health records in that
      jurisdiction. It is therefore necessary to ensure that these data are of high
      quality, and that chart information is accurately coded to meet this end. Our
      objective is to explore the potential barriers that exist for high quality data
      coding through qualitative inquiry into the roles and responsibilities of medical
      chart coders. METHODS: We conducted semi-structured interviews with 28 medical
      chart coders from Alberta, Canada. We used thematic analysis and open-coded each
      transcript to understand the process of administrative health data generation and
      identify barriers to its quality. RESULTS: The process of generating
      administrative health data is highly complex and involves a diverse workforce. As
      such, there are multiple points in this process that introduce challenges for
      high quality data. For coders, the main barriers to data quality occurred around
      chart documentation, variability in the interpretation of chart information, and
      high quota expectations. CONCLUSIONS: This study illustrates the complex nature
      of barriers to high quality coding, in the context of administrative data
      generation. The findings from this study may be of use to data users,
      researchers, and decision-makers who wish to better understand the limitations of
      their data or pursue interventions to improve data quality.

PMID- 29166906
TI  - Anaphylaxis in an emergency care setting: a one year prospective study in
      children and adults.
AB  - BACKGROUND: Current data on anaphylaxis is based on retrospective and register
      based studies. The objective of this study was to describe the epidemiology of
      anaphylaxis in a 1 year prospective study at the emergency care setting, Odense
      University Hospital, Denmark (2013-2014). METHODS: Prospective study at the
      emergency care setting, Odense University Hospital, Denmark (2013-2014). To
      identify anaphylaxis cases, records from all patients with clinical suspicion on
      anaphylaxis or a related diagnosis according to the International Classification
      of Diseases 10 and from patients treated at the emergency care setting or at
      prehospital level with adrenaline, antihistamines or glucocorticoids were
      reviewed daily. The identified cases were referred to the Allergy Center, where a
      standardized interview regarding the anaphylactic reaction was conducted.
      International guidelines were applied for the assessment of anaphylaxis and its
      pharmacological treatment. Severity of the anaphylactic reaction was evaluated
      according to Sampson's severity score. RESULTS: We identified 180 anaphylactic
      patients. Anaphylaxis represented 0.3%-0.4% of all contacts in the emergency care
      setting with an incidence rate of 26.8 cases per 100,000 person years (95% CI:
      14.3-45.8) in children and 40.4 cases per 100,000 person years (95% CI: 32.8
      49.3) in adults. Moderate to severe anaphylaxis was registered in 96% of the
      cases. Skin (96%) and respiratory (79%) symptoms were the most frequent
      registered, but 7% of cases in adults occurred without skin manifestations. The
      most common elicitor in children was food (61%), while drugs (48%) and venom
      (24%) were the main suspected elicitors in adults. Adrenaline was administered in
      25% of the cases and it was significantly less administered than glucocorticoids
      (83%) and antihistamines (91%). The mortality rate during our study period was
      0.3 cases per 100,000 person years. DISCUSSION: This is one of the first
      prospective studies on the epidemiology of anaphylaxis in children and adults,
      where the patients are identified not only based on diagnosis codes but also on
      history, symptoms and treatment and thereafter classified according to
      international diagnosis criteria for anaphylaxis. A limitation of this study is
      that only patients who gave consent to participate in the study were included.
      Furthermore, patients may have attended other hospitals during the study period.
      Therefore, the estimates are minimum figures. CONCLUSION: The prospective study
      design with a broad search profile yield a higher incidence than previously
      reported. Adrenaline was administered in a low proportion of the patients with
      moderate to severe anaphylaxis. Standardized diagnosis criteria among physicians
      treating anaphylaxis are needed.

PMID- 29166907
TI  - Quantifying seasonal and diel variation in Anopheline and Culex human biting
      rates in Southern Ecuador.
AB  - BACKGROUND: Quantifying mosquito biting rates for specific locations enables
      estimation of mosquito-borne disease risk, and can inform intervention efforts.
      Measuring biting itself is fraught with ethical concerns, so the landing rate of
      mosquitoes on humans is often used as a proxy measure. Southern coastal Ecuador
      was historically endemic for malaria (Plasmodium falciparum and Plasmodium
      vivax), although successful control efforts in the 2000s eliminated autochthonous
      transmission (since 2011). This study presents an analysis of data collected
      during the elimination period. METHODS: Human landing catch (HLC) data for three
      mosquito taxa: two malaria vectors, Anopheles albimanus and Anopheles
      punctimacula, and grouped Culex spp. were examined for this study. These data
      were collected by the National Vector Control Service of the Ministry of Health
      over a 5-year time span (2007-2012) in five cities in southern coastal Ecuador,
      at multiple households, in all months of the year, during dusk-dawn (18:00-6:00)
      hours, often at both indoor and outdoor locations. Hurdle models were used to
      determine if biting activity was fundamentally different for the three taxa, and
      to identify spatial and temporal factors influencing bite rate. Due to the many
      different approaches to studying and quantifying bite rates in the literature, a
      glossary of terms was created, to facilitate comparative studies in the future.
      RESULTS: Biting trends varied significantly with species and time. All taxa
      exhibited exophagic feeding behavior, and outdoor locations increased both the
      odds and incidence of bites across taxa. Anopheles albimanus was most frequently
      observed biting, with an average of 4.7 bites/h. The highest and lowest
      respective months for significant biting activity were March and July for An.
      albimanus, July and August for An. punctimacula, and February and July for Culex
      spp. CONCLUSIONS: Fine-scale differences in endophagy and exophagy, and temporal
      differences among months and hours exist in biting patterns among mosquito taxa
      in southern coastal Ecuador. This analysis provides detailed information for
      targeting vector control activities, and household level vector prevention
      strategies. These data were collected as part of routine vector surveillance
      conducted by the Ministry of Health, and such data have not been collected since.
      Reinstating such surveillance measures would provide important information to aid
      in preventing malaria re-emergence.

PMID- 29166908
TI  - Mathematical models for predicting human mobility in the context of infectious
      disease spread: introducing the impedance model.
AB  - BACKGROUND: Mathematical models of human mobility have demonstrated a great
      potential for infectious disease epidemiology in contexts of data scarcity. While
      the commonly used gravity model involves parameter tuning and is thus difficult
      to implement without reference data, the more recent radiation model based on
      population densities is parameter-free, but biased. In this study we introduce
      the new impedance model, by analogy with electricity. Previous research has
      compared models on the basis of a few specific available spatial patterns. In
      this study, we use a systematic simulation-based approach to assess the
      performances. METHODS: Five hundred spatial patterns were generated using various
      area sizes and location coordinates. Model performances were evaluated based on
      these patterns. For simulated data, comparison measures were average root mean
      square error (aRMSE) and bias criteria. Modeling of the 2010 Haiti cholera
      epidemic with a basic susceptible-infected-recovered (SIR) framework allowed an
      empirical evaluation through assessing the goodness-of-fit of the observed
      epidemic curve. RESULTS: The new, parameter-free impedance model outperformed
      previous models on simulated data according to average aRMSE and bias criteria.
      The impedance model achieved better performances with heterogeneous population
      densities and small destination populations. As a proof of concept, the basic
      compartmental SIR framework was used to confirm the results obtained with the
      impedance model in predicting the spread of cholera in Haiti in 2010.
      CONCLUSIONS: The proposed new impedance model provides accurate estimations of
      human mobility, especially when the population distribution is highly
      heterogeneous. This model can therefore help to achieve more accurate predictions
      of disease spread in the context of an epidemic.

PMID- 29166909
TI  - Multiscale positive feedbacks contribute to unidirectional gastric disease
      progression induced by helicobacter pylori infection.
AB  - BACKGROUND: Helicobacter Pylori (HP) is the most common risk factor for gastric
      cancer. Nearly half the world's population is infected with HP, but only a small
      percentage of those develop significant pathology. The bacteria itself does not
      directly cause cancer; rather it promotes an environment that is conducive to
      tumor formation. Upon infection, HP induces transcriptional changes in the host,
      leading to enhanced proliferation and host immune response. In addition, HP
      causes direct damage to gastric epithelial cells. RESULTS: We present a
      multiscale mechanistic model of HP induced changes. The model includes four
      modules representing the host transcriptional changes in response to infection,
      gastric atrophy, the Hedgehog pathway response, and the restriction point that
      controls cell cycle. This model was able to recapture a number of literature
      reported observations and was used as an "in silico" representation of the
      biological system for further analysis. Dynamical analysis of the model revealed
      that HP might induce the activation of multiple interplayed positive feedbacks,
      which in turn might result in a "ratchet ladder" system that promotes a
      unidirectional progression of gastric disease. CONCLUSIONS: The current
      multiscale model is able to recapitulate the observed experimental features of HP
      host interactions and provides dynamic insights on the epidemiologically observed
      heterogeneity in disease progression. This model provides a solid framework that
      can be further expanded and validated to include additional experimental
      evidence, to understand the complex multi-pathway interactions characterizing HP
      infection, and to design novel treatment protocols for HP induced diseases.

PMID- 29166910
TI  - Prevalence and genetic diversity analysis of human coronaviruses among cross
      border children.
AB  - BACKGROUND: More than a decade after the outbreak of human coronaviruses (HCoVs)
      SARS in Guangdong province and Hong Kong SAR of China in 2002, there is still no
      reoccurrence, but the evolution and recombination of the coronaviruses in this
      region are still unknown. Therefore, surveillance on the prevalence and the virus
      variation of HCoVs circulation in this region is conducted. METHODS: A total of
      3298 nasopharyngeal swabs samples were collected from cross-border children (<6
      years, crossing border between Southern China and Hong Kong SAR) showing symptoms
      of respiratory tract infection, such as fever (body temperature > 37.5  degrees
      C), from 2014 May to 2015 Dec. Viral nucleic acids were analyzed and sequenced to
      study the prevalence and genetic diversity of the four human coronaviruses. The
      statistical significance of the data was evaluated with Fisher chi-square test.
      RESULTS: 78 (2.37%; 95%CI 1.8-2.8%) out of 3298 nasopharyngeal swabs specimens
      were found to be positive for OC43 (36;1.09%), HKU1 (34; 1.03%), NL63 (6; 0.18%)
      and 229E (2;0.01%). None of SARS or MERS was detected. The HCoVs predominant
      circulating season was in transition of winter to spring, especially January and
      February and NL63 detected only in summer and fall. Complex population with an
      abundant genetic diversity of coronaviruses was circulating and they shared
      homology with the published strains (99-100%). Besides, phylogenetic evolutionary
      analysis indicated that OC43 coronaviruses were clustered into three clades
      (B,D,E), HKU1 clustered into two clades(A,B) and NL63 clustered into two
      clades(A,B). Moreover, several novel mutations including nucleotides substitution
      and the insertion of spike of the glycoprotein on the viral surface were
      discovered. CONCLUSIONS: The detection rate and epidemic trend of coronaviruses
      were stable and no obvious fluctuations were found. The detected coronaviruses
      shared a conserved gene sequences in S and RdRp. However, mutants of the epidemic
      strains were detected, suggesting continuous monitoring of the human
      coronaviruses is in need among cross-border children, who are more likely to get
      infected and transmit the viruses across the border easily, in addition to the
      general public.

PMID- 29166911
TI  - Effective strategies for scaling up evidence-based practices in primary care: a
      systematic review.
AB  - BACKGROUND: While an extensive array of existing evidence-based practices (EBPs)
      have the potential to improve patient outcomes, little is known about how to
      implement EBPs on a larger scale. Therefore, we sought to identify effective
      strategies for scaling up EBPs in primary care. METHODS: We conducted a
      systematic review with the following inclusion criteria: (i) study design:
      randomized and non-randomized controlled trials, before-and-after (with/without
      control), and interrupted time series; (ii) participants: primary care-related
      units (e.g., clinical sites, patients); (iii) intervention: any strategy used to
      scale up an EBP; (iv) comparator: no restrictions; and (v) outcomes: no
      restrictions. We searched MEDLINE, Embase, PsycINFO, Web of Science, CINAHL, and
      the Cochrane Library from database inception to August 2016 and consulted
      clinical trial registries and gray literature. Two reviewers independently
      selected eligible studies, then extracted and analyzed data following the
      Cochrane methodology. We extracted components of scaling-up strategies and
      classified them into five categories: infrastructure, policy/regulation,
      financial, human resources-related, and patient involvement. We extracted scaling
      up process outcomes, such as coverage, and provider/patient outcomes. We
      validated data extraction with study authors. RESULTS: We included 14 studies.
      They were published since 2003 and primarily conducted in low-/middle-income
      countries (n = 11). Most were funded by governmental organizations (n = 8). The
      clinical area most represented was infectious diseases (HIV, tuberculosis, and
      malaria, n = 8), followed by newborn/child care (n = 4), depression (n = 1), and
      preventing seniors' falls (n = 1). Study designs were mostly before-and-after
      (without control, n = 8). The most frequently targeted unit of scaling up was the
      clinical site (n = 11). The component of a scaling-up strategy most frequently
      mentioned was human resource-related (n = 12). All studies reported
      patient/provider outcomes. Three studies reported scaling-up coverage, but no
      study quantitatively reported achieving a coverage of 80% in combination with a
      favorable impact. CONCLUSIONS: We found few studies assessing strategies for
      scaling up EBPs in primary care settings. It is uncertain whether any strategies
      were effective as most studies focused more on patient/provider outcomes and less
      on scaling-up process outcomes. Minimal consensus on the metrics of scaling up
      are needed for assessing the scaling up of EBPs in primary care. TRIAL
      REGISTRATION: This review is registered as PROSPERO CRD42016041461 .

PMID- 29166912
TI  - Neurofilament distribution in the superior labrum and the long head of the biceps
      tendon.
AB  - BACKGROUND: The postoperative course after arthroscopic superior labrum anterior
      to posterior (SLAP) repair using suture anchors is accompanied by a prolonged
      period of pain, which might be caused by constriction of nerve fibres. The
      purpose was to histologically investigate the distribution of neurofilament in
      the superior labrum and the long head of the biceps tendon (LHBT), i.e. the
      location of type II SLAP lesions. METHODS: Ten LHBTs including the superior
      labrum were dissected from fresh human specimen and immunohistochemically stained
      against neurofilament (NF). All slides were scanned at high resolution and
      converted into tagged image file format, and regions of interest (ROIs) were
      defined as follows: ROI I-superior labrum anterior to the LHBT origin, ROI II-mid
      portion of the superior labrum at the origin of the LHBT, ROI III-superior labrum
      posterior to the LHBT origin and ROI IV-the most proximal part of the LHBT before
      its attachment to the superior labrum. The entire images were automatically
      segmented according to the defined ROIs and measured using a programmed algorithm
      specifically created for this purpose. The NF-positive cells were counted, and
      their total size and the area of other tissue were measured separately for the
      different ROIs. RESULTS: Distribution of NF-positive cells in absolute numbers
      revealed a clear but insignificantly higher amount in favour of ROI I,
      representing the superior labrum anterior to the LHBT origin. Setting ROI I at
      100%, a significant difference could be seen compared to ROI III, representing
      the superior labrum posterior to the LHBT origin (ROI I vs. ROI III with a p
      value < 0.05). CONCLUSIONS: Summarizing, the density of neurofilament is
      inhomogeneously distributed throughout the superior labrum with the highest
      number of neurofilament in the anterior superior labrum. Thus, suture placement
      in type II SLAP repair could play an important role for the postoperative pain
      related outcome.

PMID- 29166913
TI  - Socioeconomic disadvantage, fetal environment and child development: linked
      Scottish administrative records based study.
AB  - BACKGROUND: Cognitive development in childhood is negatively affected by
      socioeconomic disadvantage. This study examined whether differences in fetal
      environment might mediate the association between family socioeconomic position
      and child development. METHODS: Data were linked from the Scottish Longitudinal
      Study, maternity inpatient records and the Child Health Surveillance Programme -
      Pre School for 32,238 children. The outcome variables were based on health
      visitor assessment of gross motor, hearing and language, vision and fine motor,
      and social development. Socioeconomic position was measured using parental social
      class and highest qualification attained. Random-effects logistic regression
      models were estimated to account for multiple reviews and familial clustering.
      Mediation analysis was conducted using the Karlson-Holm-Breen method. RESULTS:
      Hearing and language, vision and fine motor, and social development were
      associated with lower parental social class and lower parental educational
      qualifications after adjustment for fetal environment. Fetal environment
      partially mediated the estimated effect of having parents without educational
      qualifications for hearing and language (beta = 0.15; 95% confidence interval
      (CI) = 0.07, 0.23), vision and fine motor (beta = 0.19; CI = 0.10, 0.28) and
      social development (beta = 0.14; CI = 0.03 to 0.25). CONCLUSIONS: Socioeconomic
      position predicted hearing and language, vision and fine motor, and social
      development but not gross motor development. For children of parents without
      educational qualifications, fetal environment appears to contribute to a part of
      the socioeconomic gradient in child development abnormalities but post-natal
      environment appears to still explain the majority of the gradient and for other
      children most of it.

PMID- 29166914
TI  - COGNAT: a web server for comparative analysis of genomic neighborhoods.
AB  - BACKGROUND: In prokaryotic genomes, functionally coupled genes can be organized
      in conserved gene clusters enabling their coordinated regulation. Such clusters
      could contain one or several operons, which are groups of co-transcribed genes.
      Those genes that evolved from a common ancestral gene by speciation (i.e.
      orthologs) are expected to have similar genomic neighborhoods in different
      organisms, whereas those copies of the gene that are responsible for dissimilar
      functions (i.e. paralogs) could be found in dissimilar genomic contexts.
      Comparative analysis of genomic neighborhoods facilitates the prediction of co
      regulated genes and helps to discern different functions in large protein
      families. AIM: We intended, building on the attribution of gene sequences to the
      clusters of orthologous groups of proteins (COGs), to provide a method for
      visualization and comparative analysis of genomic neighborhoods of evolutionary
      related genes, as well as a respective web server. RESULTS: Here we introduce the
      COmparative Gene Neighborhoods Analysis Tool (COGNAT), a web server for
      comparative analysis of genomic neighborhoods. The tool is based on the COG
      database, as well as the Pfam protein families database. As an example, we show
      the utility of COGNAT in identifying a new type of membrane protein complex that
      is formed by paralog(s) of one of the membrane subunits of the NADH:quinone
      oxidoreductase of type 1 (COG1009) and a cytoplasmic protein of unknown function
      (COG3002). REVIEWERS: This article was reviewed by Drs. Igor Zhulin, Uri Gophna
      and Igor Rogozin.

PMID- 29166915
TI  - Serum connective tissue growth factor is a highly discriminatory biomarker for
      the diagnosis of rheumatoid arthritis.
AB  - BACKGROUND: Our previous proteomic study indicated that connective tissue growth
      factor (CTGF) may be a potential biomarker for rheumatoid arthritis (RA)
      diagnosis. The aim was to assess the performance of CTGF as a biomarker of RA.
      METHOD: Serum and synovial fluid CTGF was detected using a direct high
      sensitivity sandwich ELISA kit. Serum CTGF levels were tested for discriminatory
      capacity and optimal assay cutoffs determined in a training cohort of 98 cases of
      RA with 103 healthy controls. The assay performance was then validated in a
      further cohort of 572 patients (with RA (n = 217), ankylosing spondylitis (n =
      92), gout (n = 74), osteoarthritis (n = 52), systemic lupus erythematosus (n =
      72), or primary Sjogren's syndrome (pSS) (n = 65)). RESULTS: Significant
      elevation of synovial fluid CTGF concentration was found in RA patients,
      demonstrating excellent diagnostic ability to predict RA (area under the curve
      (AUC) = 0.97). Similar results were found in serum CTGF detection. At the optimal
      cutoff value 88.66 pg/mL, the sensitivity, specificity, and the AUC was 0.86,
      0.92, and 0.92, respectively, in the training cohort. Similar performance was
      observed in the validation cohort, with sensitivity, specificity, positive
      likelihood, and negative likelihood of 0.82, 0.91, 5.74, and 0.12, respectively.
      Stronger discriminatory capacity was seen with the combination of CTGF and anti
      citrullinated protein antibody (ACPA) (AUC = 0.96) than with either ACPA or
      rheumatoid factor (RF) alone (AUC = 0.80 or 0.79, respectively). The
      discriminatory performance of serum CTGF was consistent across all inflammatory
      conditions tested (AUC >0.92 in all cases), with the sole exception of pSS. Serum
      CTGF did not vary with symptom duration or disease activity. CONCLUSIONS: Serum
      CTGF is a promising diagnostic biomarker for RA, with performance in the current
      study better than either ACPA or RF.

PMID- 29166916
TI  - Process optimization for enhancing production of cis-4-hydroxy-L-proline by
      engineered Escherichia coli.
AB  - BACKGROUND: Understanding the bioprocess limitations is critical for the
      efficient design of biocatalysts to facilitate process feasibility and improve
      process economics. In this study, a proline hydroxylation process with
      recombinant Escherichia coli expressing L-proline cis-4-hydroxylase (SmP4H) was
      investigated. The factors that influencing the metabolism of microbial hosts and
      process economics were focused on for the optimization of cis-4-hydroxy-L-proline
      (CHOP) production. RESULTS: In recombinant E. coli, SmP4H synthesis limitation
      was observed. After the optimization of expression system, CHOP production was
      improved in accordance with the enhanced SmP4H synthesis. Furthermore, the
      effects of the regulation of proline uptake and metabolism on whole-cell
      catalytic activity were investigated. The improved CHOP production by repressing
      putA gene responsible for L-proline degradation or overexpressing L-proline
      transporter putP on CHOP production suggested the important role of substrate
      uptake and metabolism on the whole-cell biocatalyst efficiency. Through
      genetically modifying these factors, the biocatalyst activity was significantly
      improved, and CHOP production was increased by twofold. Meanwhile, to further
      improve process economics, a two-strain coupling whole-cell system was
      established to supply co-substrate (alpha-ketoglutarate, alpha-KG) with a cheaper
      chemical L-glutamate as a starting material, and 13.5 g/L of CHOP was
      successfully produced. CONCLUSIONS: In this study, SmP4H expression, and L
      proline uptake and degradation, were uncovered as the hurdles for microbial
      production of CHOP. Accordingly, the whole-cell biocatalysts were metabolically
      engineered for enhancing CHOP production. Meanwhile, a two-strain
      biotransformation system for CHOP biosynthesis was developed aiming at supplying
      alpha-KG more economically. Our work provided valuable insights into the design
      of recombinant microorganism to improve the biotransformation efficiency that
      catalyzed by Fe(II)/alpha-KG-dependent dioxygenase.

PMID- 29166917
TI  - Collaborative action for person-centred coordinated care (P3C): an approach to
      support the development of a comprehensive system-wide solution to fragmented
      care.
AB  - BACKGROUND: Fragmented care results in poor outcomes for individuals with
      complexity of need. Person-centred coordinated care (P3C) is perceived to be a
      potential solution, but an absence of accessible evidence and the lack of a
      scalable 'blue print' mean that services are 'experimenting' with new models of
      care with little guidance and support. This paper presents an approach to the
      implementation of P3C using collaborative action, providing examples of early
      developments across this programme of work, the core aim of which is to
      accelerate the spread and adoption of P3C in United Kingdom primary care
      settings. METHODS: Two centrally funded United Kingdom organisations (South West
      Collaboration for Leadership in Applied Health Research and Care and South West
      Academic Health Science Network) are leading this initiative to narrow the gap
      between research and practice in this urgent area of improvement through a
      programme of service change, evaluation and research. Multi-stakeholder
      engagement and co-design are core to the approach. A whole system measurement
      framework combines outcomes of importance to patients, practitioners and health
      organisations. Iterative and multi-level feedback helps to shape service change
      while collecting practice-based data to generate implementation knowledge for the
      delivery of P3C. The role of the research team is proving vital to support
      informed change and challenge organisational practice. The bidirectional flow of
      knowledge and evidence relies on the transitional positioning of researchers and
      research organisations. RESULTS: Extensive engagement and embedded researchers
      have led to strong collaborations across the region. Practice is beginning to
      show signs of change and data flow and exchange is taking place. However, working
      in this way is not without its challenges; progress has been slow in the
      development of a linked data set to allow us to assess impact innovations from a
      cost perspective. Trust is vital, takes time to establish and is dependent on the
      exchange of services and interactions. If collaborative action can foster P3C it
      will require sustained commitment from both research and practice. This approach
      is a radical departure from how policy, research and practice traditionally work,
      but one that we argue is now necessary to deal with the most complex health and
      social problems.

PMID- 29166918
TI  - Engineering Bacillus megaterium for production of functional intracellular
      materials.
AB  - BACKGROUND: Over the last 10-15 years, a technology has been developed to
      engineer bacterial poly(3-hydroxybutyrate) (PHB) inclusions as functionalized
      beads, for applications such as vaccines, diagnostics and enzyme immobilization.
      This has been achieved by translational fusion of foreign proteins to the PHB
      synthase (PhaC). The respective fusion protein mediates self-assembly of PHB
      inclusions displaying the desired protein function. So far, beads have mainly
      been produced in recombinant Escherichia coli, which is problematic for some
      applications as the lipopolysaccharides (LPS) co-purified with such inclusions
      are toxic to humans and animals. RESULTS: In this study, we have bioengineered
      the formation of functional PHB inclusions in the Gram-positive bacterium
      Bacillus megaterium, an LPS-free and established industrial production host. As
      B. megaterium is a natural PHB producer, the PHB-negative strain PHA05 was used
      to avoid any background PHB production. Plasmid-mediated T7 promoter-driven
      expression of the genes encoding beta-ketothiolase (phaA), acetoacetyl-CoA
      reductase (phaB) and PHB synthase (phaC) enabled PHB production in B. megaterium
      PHA05. To produce functionalized PHB inclusions, the N- and C-terminus of PhaC
      was fused to four and two IgG binding Z-domains from Staphylococcus aureus,
      respectively. The ZZ-domain PhaC fusion protein was strongly overproduced at the
      surface of the PHB inclusions and the corresponding isolated ZZ-domain displaying
      PHB beads were found to purify IgG with a binding capacity of 40-50 mg IgG/g
      beads. As B. megaterium has the ability to sporulate and respective endospores
      could co-purify with cellular inclusions, a sporulation negative production
      strain was generated by disrupting the spoIIE gene in PHA05. This strain did not
      produce spores when tested under sporulation inducing conditions and it was still
      able to synthesize ZZ-domain displaying PHB beads. CONCLUSIONS: This study
      provides proof of concept for the successful genetic engineering of B. megaterium
      as a host for the production of functionalized PHB beads. Disruption of the
      spoIIE gene rendered B. megaterium incapable of sporulation but particularly
      suitable for production of functionalized PHB beads. This sporulation-negative
      mutant represents an improved industrial production strain for biotechnological
      processes otherwise impaired by the possibility of endospore formation.

PMID- 29166919
TI  - Similar short-term clinical response to high-dose versus low-dose methotrexate in
      monotherapy and combination therapy in patients with rheumatoid arthritis.
AB  - BACKGROUND: Aiming at rapid decrease of disease activity, there has been a trend
      to start with higher doses of methotrexate (MTX) in patients newly diagnosed with
      rheumatoid arthritis (RA), both as monotherapy and in combination with other
      antirheumatic drugs. We aimed to study the relationship between clinical response
      and MTX dose as monotherapy or combination therapy in patients with early RA.
      METHODS: Disease-modifying anti-rheumatic drug (DMARD)-naive patients with early
      RA, from a large international observational database, the METEOR database, were
      selected if MTX was part of their initial treatment. Patients were divided into
      four groups: MTX monotherapy, MTX + convention synthetic (cs)DMARDs, MTX +
      glucocorticoids or MTX + biologic (b)DMARDs. MTX dose was dichotomized: low dose
      <=10 mg/week; high dose >=15 mg/week. Linear mixed model analyses for the Disease
      Activity Score (DAS), DAS in 28 joints (DAS28) and Health Assessment
      Questionnaire (HAQ) were performed in each medication group, with MTX dose and
      time as covariates. Outcomes were assessed from baseline until 3-6 months follow
      up. Associations were adjusted for potential confounding by indication using
      propensity score (PS) modelling. RESULTS: For patients starting MTX monotherapy
      (n = 523), MTX + csDMARDs (n = 266) or MTX + glucocorticoids (n = 615), the PS
      adjusted effects of MTX dose (high versus low) on the DAS, DAS28 and HAQ were
      small and not clinically meaningful. Patients starting MTX + bDMARDs were
      disregarded due to low numbers (n =11). CONCLUSIONS: In patients newly diagnosed
      with RA, no clinical benefit of high compared to low initial MTX doses was found
      for MTX monotherapy or for MTX combination therapy with csDMARDs or
      glucocorticoids.

PMID- 29166920
TI  - A 3D epithelial-mesenchymal co-culture model of human bronchial tissue
      recapitulates multiple features of airway tissue remodeling by TGF-beta1
      treatment.
AB  - BACKGROUND: The collagen gel contraction assay measures gel size to assess the
      contraction of cells embedded in collagen gel matrices. Using the assay with lung
      fibroblasts is useful in studying the lung tissue remodeling process in wound
      healing and disease development. However, the involvement of bronchial epithelial
      cells in this process should also be investigated. METHODS: We applied a layer of
      mucociliary differentiated bronchial epithelial cells onto collagen gel matrices
      with lung fibroblasts. This co-culture model enables direct contact between
      epithelial and mesenchymal cells. We stimulated the culture with transforming
      growth factor (TGF) beta1 as an inducer of tissue remodeling for 21 days, and
      measured gel size, histological changes, and expression of factors related to
      extracellular matrix homeostasis. RESULTS: TGF-beta1 exerted a concentration
      dependent effect on collagen gel contraction and on contractile myofibroblasts in
      the mesenchymal collagen layer. TGF-beta1 also induced expression of the
      mesenchymal marker vimentin in the basal layer of the epithelium, suggesting the
      induction of epithelial-mesenchymal transition. In addition, the expression of
      various genes encoding extracellular matrix proteins was upregulated. Fibrotic
      tenascin-C accumulated in the sub-epithelial region of the co-culture model.
      CONCLUSION: Our findings indicate that TGF-beta1 can affect both epithelial and
      mesenchymal cells, and induce gel contraction and structural changes. Our novel
      in vitro co-culture model will be a useful tool for investigating the roles of
      epithelial cells, fibroblasts, and their interactions in the airway remodeling
      process.

PMID- 29166921
TI  - Identification of epidermal growth factor receptor-positive glioblastoma using
      lipid-encapsulated targeted superparamagnetic iron oxide nanoparticles in vitro.
AB  - BACKGROUND: Targeted superparamagnetic iron oxide (SPIO) nanoparticles have
      emerged as a promising biomarker detection tool for molecular magnetic resonance
      (MR) image diagnosis. To identify patients who could benefit from Epidermal
      growth factor receptor (EGFR)-targeted therapies, we introduce lipid-encapsulated
      SPIO nanoparticles and hypothesized that anti-EGFR antibody cetuximab conjugated
      of such nanoparticles can be used to identify EGFR-positive glioblastomas in non
      invasive T2 MR image assays. The newly introduced lipid-coated SPIOs, which
      imitate biological cell surface and thus inherited innate nonfouling property,
      were utilized to reduce nonspecific binding to off-targeted cells and prevent
      agglomeration that commonly occurs in nanoparticles. RESULTS: The synthesized
      targeted EGFR-antibody-conjugated SPIO (EGFR-SPIO) nanoparticles were
      characterized using dynamic light scattering, zeta potential assays, gel
      electrophoresis mobility shift assays, transmission electron microscopy (TEM)
      images, and cell line affinity assays, and the results showed that the
      conjugation was successful. The targeting efficiency of the synthesized EGFR-SPIO
      nanoparticles was confirmed through Prussian blue staining and TEM images by
      using glioblastoma cell lines with high or low EGFR expression levels. The EGFR
      SPIO nanoparticles preferentially targeted U-251 cells, which have high EGFR
      expression, and were internalized by cells in a prolonged incubation condition.
      Moreover, the T2 MR relaxation time of EGFR-SPIO nanoparticles could be used for
      successfully identifying glioblastoma cells with elevated EGFR expression in
      vitro and distinguishing U-251 cells from U-87MG cells, which have low EFGR
      expression. CONCLUSION: These findings reveal that the lipid-encapsulated EGFR
      SPIO nanoparticles can specifically target cells with elevated EGFR expression in
      the three tested human glioblastoma cell lines. The results of this study can be
      used for noninvasive molecular MR image diagnosis in the future.

PMID- 29166922
TI  - Herpes simplex type 1 pneumonitis and acute respiratory distress syndrome in a
      patient with chronic lymphatic leukemia: a case report.
AB  - BACKGROUND: Pulmonary pathogenicity of herpes simplex virus type 1 in patients in
      intensive care without classic immunosuppression as well as the necessity of
      antiviral treatment in the case of herpes simplex virus detection in respiratory
      specimens in these patients is controversial. We present a case of acute
      respiratory distress syndrome in a patient with stable chronic lymphatic leukemia
      not requiring treatment, in whom we diagnosed herpes simplex virus type 1
      bronchopneumonitis based on herpes simplex virus type 1 detection in
      bronchoalveolar lavage fluid and clinical response to antiviral treatment. CASE
      PRESENTATION: A 72-year-old white man presented with symptoms of lower
      respiratory tract infection. His medical history was significant for chronic
      lymphatic leukemia, which had been stable without treatment, arterial
      hypertension, multiple squamous cell carcinomas of the scalp, and alcohol
      overuse. Community-acquired pneumonia was suspected and appropriate broad
      spectrum antibacterial treatment was initiated. Within a few hours, rapid
      respiratory deterioration led to cardiac arrest. He was successfully
      resuscitated, but developed acute respiratory distress syndrome. Furthermore, he
      remained febrile and inflammation markers remained elevated despite antibacterial
      treatment. Polymerase chain reaction from bronchoalveolar lavage fluid and viral
      culture from tracheobronchial secretions tested positive for herpes simplex virus
      type 1. We initiated antiviral treatment with acyclovir. Concomitantly we further
      escalated the antibacterial treatment, although no bacterial pathogen had been
      isolated at any point. Defervescence occurred rapidly and his C-reactive protein
      and leukocyte levels decreased. He was successfully weaned from mechanical
      ventilation, transferred to the ward, and eventually discharged to home.
      CONCLUSIONS: Herpes simplex virus should be considered a cause for lower
      respiratory tract infection in critically ill patients, especially in the setting
      of an underlying disease.

PMID- 29166923
TI  - Childhood Takayasu arteritis: disease course and response to therapy.
AB  - BACKGROUND: Takayasu arteritis (TAK) is a large vessel vasculitis that rarely
      affects children. Data on childhood TAK are scarce. The aim of this study was to
      analyze the presenting features, course and outcome of children with TAK, compare
      efficacy of treatment regimens and identify high-risk factors for adverse
      outcome. METHODS: A single-center cohort study of consecutive children fulfilling
      the EULAR/PRINTO/PReS criteria for childhood TAK between 1986 and 2015 was
      performed. Clinical phenotypes, laboratory markers, imaging features, disease
      course and treatment were documented. Disease activity was assessed using the
      Pediatric Vasculitis Disease Activity Score at each visit. OUTCOME: disease flare
      defined as new symptoms and/or increased inflammatory markers necessitating
      therapy escalation and/or new angiographic lesions, or death. ANALYSIS: logistic
      regression tested relevant variables for flare. Kaplan-Meier analyses compared
      treatment regimens. RESULTS: Twenty-seven children were included; 74% were
      female, median age at diagnosis was 12.4 years. Twenty-two (81%) children
      presented with active disease at diagnosis. Treatment regimens included
      corticosteroids alone (15%), corticosteroids plus methotrexate (37%),
      cyclophosphamide (19%), or a biologic agent (11%). Adverse outcomes were
      documented in 14/27 (52%) children: two (7%) died within 6 months of diagnosis,
      and 13 (48%) experienced disease flares. The 2-year flare-free survival was 80%
      with biologic treatments compared to 43% in non-biologic therapies (p = 0.03); at
      last follow-up, biologic therapies resulted in significantly higher rates of
      inactive disease (p = 0.02). No additional outcome predictor was identified.
      CONCLUSIONS: Childhood TAK carries a high disease burden; half of the children
      experienced flares and 7% died. Biologic therapies were associated with better
      control of disease activity.

PMID- 29166924
TI  - Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic
      onset juvenile idiopathic arthritis patients from the BIKER registry.
AB  - BACKGROUND: Treatment of systemic onset juvenile idiopathic arthritis JIA (sJIA),
      although dramatically improved, remains a challenge. Experience from clinical
      practice will be presented using data from the German Biologics register (BiKeR)
      for evaluation of efficacy and safety of treatment with etanercept (ETA),
      tocilizumab (TOC) and the interleukin-1 inhibitors anakinra and canakinumab (IL
      1i) in sJIA. METHODS: Patients with sJIA documented in the BIKeR register, who
      were exposed to ETA, TOC or IL-1i were identified. Baseline demographics,
      clinical characteristics and disease activity parameters have been documented.
      Efficacy was determined using the JIA-American College of Rheumatology (ACR)
      response criteria and the Juvenile Disease Activity Score 10 (JADAS10). An
      intention-to-treat analysis was performed and patients who discontinued due to
      inefficacy or intolerance were analysed as non-responders. Safety assessments
      were based on adverse events (AEs) reports. RESULTS: Since 2000, 245 sJIA
      patients (50.3% male) exposed to biologic agents have been identified: 143
      patients treated with ETA, 71 with TOC and 60 with IL-1i (anakinra 38,
      canakinumab 22). All patients received systemic steroids for pre-treatment but
      less frequently with TOC and IL-1i than with ETA for concomitant treatment. At
      baseline, the ETA cohort had fewer systemic disease manifestations but more
      active joints. The JIA-ACR 30/50/70/90 response over a period of 24 months was
      reached more often in the IL-1i and TOC cohort than with ETA. ETA/TOC/IL1i JADAS
      remission (JADAS <=1) was reached in 20%/37%/52%, minimal disease activity (JADAS
      <=3.8 in 35%/61%/68% and ACR inactive disease in 24%/33%/56%). As compared to
      ETA, rates of AEs were significantly higher in the TOC cohort (risk ratio (RR)
      5.3/patient-year; p < 0.0001) and serious AE were observed more frequently with
      TOC (RR 2.5; p < 0.5) and IL1i (2.9; p < 0.01). CONCLUSIONS: A large proportion
      of patients gained significant response to treatment especially with TOC or IL
      1is. After 6 months on treatment, JADAS remission was reached by up to half of
      patients while up to two thirds reached JADAS minimal disease activity. ETA has
      been used in the past but it is clearly less effective and its use in systemic
      JIA has markedly decreased in Germany.

PMID- 29166925
TI  - The effects of chemoradiotherapy on recurrence and survival in locally advanced
      rectal cancers with curative total mesorectal excision: a prospective,
      nonrandomized study.
AB  - BACKGROUND: There are only two prospective, randomized studies comparing
      preoperative long-term chemoradiotherapy and postoperative chemoradiotherapy in
      locally advanced rectal cancer (LARC); however, conflicting results in terms of
      locoregional recurrence (LR) and survival rates have been reported. This
      prospective study aims to compare the effects of preoperative versus
      postoperative chemoradiotherapy on recurrence and survival rates in LARC
      patients. METHODS: From January 2003 to January 2016, a total of 336 eligible
      patients who were clinically diagnosed with LARC (T3-T4 tm or node-positive
      disease) were prospectively assigned into preoperative chemoradiotherapy (n =
      177) and postoperative chemoradiotherapy (n = 159) groups. The preoperative
      treatment consisted of 50.4 Gy total dose of radiotherapy (delivered in fractions
      of 1.8 Gy) and concomitant two cycles chemotherapy of 5-fluorouracil and
      leucovorin. The patients in the preoperative group underwent curative total
      mesorectal excision (TME) following long-term chemoradiotherapy. Surgery was
      performed 8 (range 4-12) median weeks after the completion of the
      chemoradiotherapy. Similar protocol was administered to the postoperative group 4
      weeks after the operation. Four cycles of adjuvant chemotherapy were added to the
      groups. The primary end points were locoregional recurrences and 5-year cancer
      specific, overall, and disease-free survivals. RESULTS: The mean follow-up period
      was 60.4 (range 12 to 168) months. Five-year cumulative incidence of locoregional
      recurrence (LR) was 7.4% in the preoperative group and 13.4% in the postoperative
      group (p = 0.021). Five-year cancer-specific survival (CSS) was 87.5% in the
      preoperative group and 80% in the postoperative group (p = 0.022). Overall
      survival (OS) was 79.8 versus 74.7% (p = 0.064), disease-free survival (DFS) was
      75.2 versus 64.8% (p = 0.062), and severe late toxicity was 7.4 versus 13.2% (p =
      0.002), respectively. The rate of patient compliance was higher in the
      preoperative group (p < 0.001). CONCLUSIONS: Preoperative chemoradiotherapy, as
      compared with postoperative chemoradiotherapy, significantly improved local
      control, patient compliance, CSS, and late toxicity and suggested a trend toward
      improved overall and disease-free survival.

PMID- 29166926
TI  - Protocol for a systematic review and meta-analysis on the clinical outcomes and
      cost of deep inferior epigastric perforator (DIEP) flap versus implants for
      breast reconstruction.
AB  - BACKGROUND: Mastectomy in the context of breast malignancy can have a profoundly
      negative impact on a woman's self-image, impairing personal, sexual and social
      relationships. The deep inferior epigastric perforator (DIEP) flap and implants
      are the two commonest reconstructive modalities that can potentially overcome
      this psychological trauma. The comparative data on clinical outcomes and costs of
      the two modalities is limited. We aim to synthesise the current evidence on DIEP
      versus implants to establish which is the superior technique for breast
      reconstruction, in terms of clinical outcomes and cost-effectiveness. METHODS: A
      comprehensive search will be undertaken of EMBASE, MEDLINE, Google Scholar,
      CENTRAL and Science citation index databases (1994 up to August 2017) to identify
      studies relevant for the review. Primary human studies evaluating clinical
      outcomes and cost of DIEP and implant-based reconstruction in context of breast
      malignancy will be included. Primary outcomes will be patient satisfaction and
      cosmetic outcome from patient-reported outcome measures (scores from validated
      tools, e.g. BREAST-Q tool), complications and cost-analysis. The secondary
      outcomes will be duration of surgery, number of surgical revisions, length of
      stay, availability of procedures and total number of clinic visits. DISCUSSION:
      This will be the first systematic review and meta-analysis in available
      literature comparing the clinical outcomes and cost-effectiveness of DIEP and
      implants for breast reconstruction. This review is expected to guide worldwide
      clinical practice for breast reconstruction. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42017072557 .

PMID- 29166927
TI  - Safety of transtympanic application of probiotics in a chinchilla animal model.
AB  - BACKGROUND: Chronic suppurative otitis media can be recalcitrant and difficult to
      treat, particularly with the increasing occurrence of antibiotic resistance.
      Lactobacillus plantarum is a probiotic that has been shown to decrease S. aureus
      and P. aeruginosa growth in wounds, making it a good candidate for the treatment
      of chronic suppurative otitis media. However, before it can be applied in the
      ear, its ototoxicity potential must be evaluated. METHODS: A prospective
      controlled trial was conducted in a chinchilla animal model at the Animal care
      research facilities of the Montreal Children's Hospital Research Institute to
      determine whether Lactobacillus plantarum is ototoxic when applied
      transtympanically. Ten chinchillas each had one ear randomly assigned to receive
      109 CFU/mL of Lactobacillus plantarum solution, while the contralateral ear
      received saline. Auditory brainstem responses were measured bilaterally at 8, 20,
      25 kHz before, at 7-10 days after application, and at 28 days after application
      of probiotic or saline. Facial nerve and vestibular function were assessed
      clinically. RESULTS: There were no statistically significant differences in
      hearing thresholds between control and experimental ears at 28 days after
      application. A difference of 11 dB was noted in the 25 kHz range at day 7-10, but
      resolved by day 28. No animals receiving probiotics developed vestibular nerve
      dysfunction. There was no histologic evidence of auditory hair cell damaged
      evidenced by scanning electron microscopy. CONCLUSION: Our study suggests that a
      single application of Lactobacillus plantarum at 109 CFU/mL does not cause
      ototoxicity in a chinchilla animal model. These preliminary safety evaluations
      and the pathogen inhibitory effects of L. plantarum demonstrated by previous
      studies present this probiotic as a candidate of interest for further
      investigation.

PMID- 29166928
TI  - Effects of long-term weekly iron and folic acid supplementation on lower genital
      tract infection - a double blind, randomised controlled trial in Burkina Faso.
AB  - BACKGROUND: Provision of routine iron supplements to prevent anaemia could
      increase the risk for lower genital tract infections as virulence of some
      pathogens depends on iron availability. This trial in Burkina Faso assessed
      whether weekly periconceptional iron supplementation increased the risk of lower
      genital tract infection in young non-pregnant and pregnant women. METHODS:
      Genital tract infections were assessed within a double blind, controlled, non
      inferiority trial of malaria risk among nulliparous women, randomised to receive
      either iron and folic acid or folic acid alone, weekly, under direct observation
      for 18 months. Women conceiving during this period entered the pregnancy cohort.
      End assessment (FIN) for women remaining non-pregnant was at 18 months. For the
      pregnancy cohort, end assessment was at the first scheduled antenatal visit
      (ANC1). Infection markers included Nugent scores for abnormal flora and bacterial
      vaginosis (BV), T. vaginalis PCR, vaginal microbiota, reported signs and
      symptoms, and antibiotic and anti-fungal prescriptions. Iron biomarkers were
      assessed at baseline, FIN and ANC1. Analysis compared outcomes by intention to
      treat and in iron replete/deficient categories. RESULTS: A total of 1954 women
      (mean 16.8 years) were followed and 478 (24.5%) became pregnant. Median
      supplement adherence was 79% (IQR 59-90%). Baseline BV prevalence was 12.3%. At
      FIN and ANC1 prevalence was 12.8% and 7.0%, respectively (P < 0.011). T.
      vaginalis prevalence was 4.9% at FIN and 12.9% at ANC1 (P < 0.001). BV and T.
      vaginalis prevalence and microbiota profiles did not differ at trial end-points.
      Iron-supplemented non-pregnant women received more antibiotic treatments for non
      genital infections (P = 0.014; mainly gastrointestinal infections (P = 0.005),
      anti-fungal treatments for genital infections (P = 0.014) and analgesics (P =
      0.008). Weekly iron did not significantly reduce iron deficiency prevalence. At
      baseline, iron-deficient women were more likely to have normal vaginal flora (P =
      0.016). CONCLUSIONS: Periconceptional weekly iron supplementation of young women
      did not increase the risk of lower genital tract infections but did increase
      general morbidity in the non-pregnant cohort. Unabsorbed gut iron due to malaria
      could induce enteric infections, accounting for the increased administration of
      antibiotics and antifungals in the iron-supplemented arm. This finding reinforces
      concerns about routine iron supplementation in highly malarious areas. TRIAL
      REGISTRATION: Trial registration number NCT01210040 . Registered with
      Clinicaltrials.gov on 27 September 2010.

PMID- 29166929
TI  - Prevalence of dietary supplement use and associated factors among female college
      students in Saudi Arabia.
AB  - BACKGROUND: The economic boom in Saudi Arabia indirectly prompted the use of
      dietary supplements in the last two decades. Our aim is to investigate the
      prevalence of dietary supplement use and its association with
      sociodemographic/lifestyle characteristics among Saudi female students. METHODS:
      In this cross-sectional study, 534 female participants (>=19 years of age)
      completed a self-administered questionnaire that include sociodemographic and
      lifestyle characteristics, perceived health status, dietary supplement use,
      general awareness, attitudes and behavior. RESULTS: In all participants, the
      prevalence of dietary supplement use was 76.6% (n = 409). High level of education
      (p = 0.002) and more physical activity (p = 0.008) exhibited a significant
      positive association with users than to non-users. The frequency showed that beta
      carotene (54.2%), chamomile (54.2%), and glucosamine (53.8%) were the most
      preferred diet supplements under the category "when needed". Cod liver oil
      (71.3%), omega 3 (68.3%), multi-vitamins (61.5%), ginseng (60%), and vitamin A
      (60%), were mostly used "from time to time". Multi-minerals (34.4%) were the
      preferred choice when it comes to daily use. The main reasons for supplement use
      were to "maintain healthy hair" and "injury and illness" (both 26.2%). About
      38.4% were not aware and 30.3% disagree on differences taking supplements with or
      without consulting a medical professional. About 36.7% lack information about
      side effects while, 35.0% were unaware about any health effect of dietary
      supplements. CONCLUSION: The prevalence of dietary supplement use was high in
      Saudi female students and was significantly associated with sociodemographic and
      lifestyle factors.

PMID- 29166930
TI  - A prospective cohort study identifying risk factors for shoulder injuries in
      adolescent elite handball players: the Karolinska Handball Study (KHAST) study
      protocol.
AB  - BACKGROUND: Handball is a physical contact sport that includes frequent overhead
      throwing, and this combination leads to a high rate of shoulder injuries. Several
      factors have been associated with shoulder injuries in overhead athletes, but
      strong scientific evidence is lacking for most suggested risk factors. We
      therefore designed the Karolinska Handball Study (KHAST) with the aim to identify
      risk factors for shoulder injuries in adolescent male and female elite handball
      players studying at handball-profiled secondary schools in Sweden. Secondary
      objectives are to investigate whether shoulder function changes during the
      competition season and whether the physical profile of the players changes during
      their time in secondary school. METHODS: Players aged 15 to 19 years were
      included during the pre-season period of the 2014-2015 and the 2015-2016 seasons.
      At inclusion, players signed informed consent and filled in a questionnaire
      regarding playing position, playing level, previous handball experience, history
      of shoulder problems and athletic identity. Players also completed a detailed
      test battery at baseline evaluating the shoulder, neck and trunk. Players were
      then prospectively monitored weekly during the 2014-2015 and/or 2015-2016
      competitive seasons regarding injuries and training/match workload. Results from
      the annual routine physical tests in the secondary school curriculum including
      bench press, deep squat, hand grip strength, clean lifts, squat jumps, counter
      movement jumps, <30 m sprints, chins, dips and Cooper's test will be collected
      until the end of the competitive season 2017-2018. The primary outcome is the
      incidence of shoulder injuries and shoulder problems. The secondary outcome is
      the prevalence of shoulder injuries and shoulder problems. DISCUSSION: Shoulder
      problems are frequent among handball players and a reduction of these injuries is
      therefore warranted. However, in order to introduce appropriate preventive
      measures, a detailed understanding of the underlying risk factors is needed. Our
      study has a high potential to identify important risk factors for shoulder
      injuries in adolescent elite handball players owing to a large study sample, a
      high response rate, data collection during consecutive seasons, and recording of
      potential confounding factors.

PMID- 29166931
TI  - Elevated LRRK2 autophosphorylation in brain-derived and peripheral exosomes in
      LRRK2 mutation carriers.
AB  - Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene can cause
      late-onset Parkinson disease (PD). LRRK2 mutations increase LRRK2 kinase
      activities that may increase levels of LRRK2 autophosphorylation at serine 1292
      (pS1292) and neurotoxicity in model systems. pS1292-LRRK2 protein can be packaged
      into exosomes and measured in biobanked urine. Herein we provide evidence that
      pS1292-LRRK2 protein is robustly expressed in cerebral spinal fluid (CSF)
      exosomes. In a novel cohort of Norwegian subjects with and without the G2019S
      LRRK2 mutation, with and without PD, we quantified levels of pS1292-LRRK2, total
      LRRK2, and other exosome proteins in urine from 132 subjects and in CSF from 82
      subjects. CSF and urine were collected from the same morning clinic visit in 55
      of the participants. We found that total LRRK2 protein concentration was similar
      in exosomes purified from either CSF or urine but the levels did not correlate.
      pS1292-LRRK2 levels were higher in urinary exosomes from male and female subjects
      with a LRRK2 mutation. Male LRRK2 mutation carriers without PD had intermediate
      pS1292-LRRK2 levels compared to male carriers with PD and controls. However,
      female LRRK2 mutation carriers without PD had the same pS1292-LRRK2 levels
      compared to female carriers with PD. pS1292-LRRK2 levels in CSF exosomes were
      near saturated in most subjects, ten-fold higher on average than pS1292-LRRK2
      levels in urinary exosomes, irrespective of LRRK2 mutation status or PD
      diagnosis. These results provide insights into the effects of LRRK2 mutations in
      both the periphery and brain in a well-characterized clinical population and show
      that LRRK2 protein in brain exosomes may be much more active than in the
      periphery in most subjects.

PMID- 29166932
TI  - BAP1: case report and insight into a novel tumor suppressor.
AB  - BACKGROUND: BRCA1-Associated-Protein 1 (BAP1) is a dynamic tumor suppressor
      which, when mutated, has been associated with an increased risk of uveal
      melanoma, cutaneous melanoma, mesothelioma, and several other cancers. Germline
      BAP1 mutations have been extensively studied, where they have been found to cause
      hereditary cancer susceptibility. However, their sporadic counterparts, tumors
      that display a loss of BAP1 expression due to somatically arising mutations in
      the BAP1 gene, remain a poorly described entity. CASE PRESENTATION: Here we
      present the case of a 49-year-old female who presented with an asymptomatic dome
      shaped pink papule on the dorsal foot which was found on biopsy to be deficient
      in the BAP1 tumor suppressor. While the patient's family history did not suggest
      the presence of a familial cancer syndrome, germline genetic testing was
      performed and was negative. The patient underwent surgical excision of this
      sporadically appearing "BAPoma" by Mohs surgery. CONCLUSIONS: Given the
      relatively banal clinical appearance of these dome-shaped neoplasms, sporadic
      BAPomas may often be overlooked by clinicians and dermatologists. In addition to
      providing a representative case, here we also provide a synopsis of the current
      understanding of these neoplasms, both in terms of the histopathological
      features, as well as the molecular mechanisms underlying BAP1 function and its
      ability to prevent tumorigenesis.

PMID- 29166933
TI  - Correlation between facet tropism and lumbar degenerative disease: a
      retrospective analysis.
AB  - BACKGROUND: The aim of this study was to investigate the correlation between
      facet tropism and spinal degenerative diseases, such as degenerative lumbar
      spondylolisthesis, degenerative lumbar scoliosis, and lumbar disc herniation.
      METHODS: This study retrospectively analysed clinical data from the Department of
      Orthopaedics at The First Affiliated Hospital of Nanchang University. Ninety-two
      patients were diagnosed with lumbar spondylolisthesis, 64 patients with
      degenerative scoliosis, and 86 patients with lumbar disc herniation between 1
      October 2014 and 1 October 2016. All patients were diagnosed using 3.0 T magnetic
      resonance imaging and underwent conservative or operative treatment. Facet
      tropism was defined as greater than a ten degree between the facet joint angles
      on both sides. RESULTS: For L3-L4 degenerative lumbar spondylolisthesis, one out
      of six cases had tropism compared to seven out of the 86 controls (p = 0.474). At
      the L4-L5 level, 17/50 cases had tropism compared to 4/42 cases in the control
      group (p = 0.013). At the L5-S1 level, 18/36 cases had tropism compared to 7/56
      controls (p = 0.000). For degenerative lumbar scoliosis at the L1-L5 level,
      83/256 cases had tropism as compared to 36/256 controls (p = 0.000). For L3-L4
      lumbar disc herniation two out of eight cases had tropism compared to 14/78
      controls (p = 0.625). At the L4-L5 level, 19/44 cases had tropism compared to
      four out of 42 controls (p = 0.001). At the L5-S1 level, 24/34 cases had tropism
      compared to 10/52 controls (p = 0.000). CONCLUSION: At the L4-5 and L5-S1 levels,
      facet tropism is associated with degenerative spondylolisthesis. In the
      degenerative lumbar scoliosis group, the number of case with facet tropism was
      significantly higher than that of the control group. Facet tropism was associated
      with lumbar disc herniation at the L4-5 and L5-S1 levels. Overall, in these three
      lumbar degenerative diseases, facet tropism is a common phenomenon.

PMID- 29166934
TI  - Arthroscopic patellar release for treatment of chronic symptomatic patellar
      tendinopathy: long-term outcome and influential factors in an athletic
      population.
AB  - BACKGROUND: Arthroscopic patellar release (APR) is utilized for minimally
      invasive surgical treatment of patellar tendinopathy. Evidence regarding long
      term success following the procedure is limited. Also, the influence of age and
      preoperative performance level, are incompletely understood. The aim of this
      study was to investigate whether APR translates into sustained pain relief over a
      long-term follow-up in athletes undergoing APR. Furthermore, we analyzed if age
      influences clinical and functional outcome measures in APR. METHODS: Between 1998
      and 2010, 30 competitive and recreational athletes were treated with APR due to
      chronic refractory patellar tendinopathy. All data were analyzed retrospectively.
      Demographic data, such as age or level of performance prior to injury were
      extracted. Clinical as well as functional outcome measures (Swedish Victorian
      Institute of sport assessment for patella (VISA-P), the modified Blazina score,
      pain level following exercise, return to sports, and subjective knee function
      were assessed pre- and postoperatively. RESULTS: In total, 30 athletes were
      included in this study. At follow-up (8.8 +/- 2.82 years), clinical and
      functional outcome measures such as the mean Blazina score, VISA-P, VAS, and
      subjective knee function revealed significant improvement compared to before
      surgery (P < 0.001). The mean time required for return to sports was 4.03 +/-
      3.18 months. After stratification by age, patients younger than 30 years of age
      yielded superior outcome in the mean Blazina score and pain level when compared
      to patients >=30 years (P = 0.0448). At 8 years of follow-up, patients yielded
      equivalent clinical and functional outcome scores compared to our previous
      investigation after four years following APR. CONCLUSION: In summary, APR can be
      regarded a successful, minimally invasive, and sustained surgical technique for
      the treatment of patella tendinopathy in athletes. Younger age at surgery may be
      associated with improved clinical and functional outcome following APR.

PMID- 29166935
TI  - Phytochemical and pharmacological evaluation of ethanolic extract of Lepisanthes
      rubiginosa L. leaves.
AB  - BACKGROUND: The current study was conducted to evaluate the antioxidant,
      analgesic, antihyperglycemic, neuropharmacological and antidiarrheal activities
      of ethanolic extract of Lepisanthes rubiginosa L. leaves in different
      experimental models. METHODS: Quantitative and qualitative analysis were done by
      TLC (thin layer chromatography) and DPPH (1,1-diphenyl-2-picrylhydrazyl) free
      radical scavenging assay. Analgesic, antihyperglycemic and antidiarrheal
      activities were evaluated using acetic acid induced writhing in mice, oral
      glucose tolerance test and castor oil induced diarrhea, respectively.
      Neuropharmacological activity was investigated in mice using both Open Field and
      Hole Board methods. RESULTS: TLC analysis indicated the presence of antioxidant
      compounds in the extract we used. The extract showed IC50 value was 31.62 MUg/mL
      whereas the standard ascorbic acid showed 12.02 MUg/mL. In acetic acid induced
      writhing assay, the extract showed 46.07% and 58.43% writhing inhibition at the
      doses of 250 mg/kg and 500 mg/kg body weight, respectively whereas standard
      diclofenac-Na (25 mg/kg) showed 86.52% writhing inhibition. The plant extract
      showed significant (p < 0.05) antihyperglycemic activity on mice as compared to
      control groups. In neuropharmacological activity assay the experimental animal
      showed a noticeable decrease in locomotion by showing a decrease in number of
      square crossed and head dipping at both doses (250 mg/kg & 500 mg/kg). In
      antidiarrheal activity test, the plant extract at the doses of 250 mg/kg and 500
      mg/kg showed percent inhibition of defecation 57.89 and 77.19 respectively,
      whereas standard loperamide (3 mg/kg) showed percent inhibition of defecation
      88.59. CONCLUSION: The results demonstrated that the extract has potential
      antioxidant, analgesic, antihyperglycemic, neuropharmacological and antidiarrheal
      activity.

PMID- 29166936
TI  - Detection of pathogens by real-time PCR in adult patients with acute exacerbation
      of bronchial asthma.
AB  - BACKGROUND: Respiratory tract infection is a major cause of acute exacerbation of
      bronchial asthma (AEBA). Although recent findings suggest that common bacteria
      are causally associated with AEBA, a comprehensive epidemiologic analysis of
      infectious pathogens including common/atypical bacteria and viruses in AEBA has
      not been performed. Accordingly, we attempted to detect pathogens during AEBA by
      using real-time polymerase chain reaction (PCR) in comparison to conventional
      methods. METHODS: We prospectively enroled adult patients with AEBA from August
      2012 to March 2014. Infectious pathogens collected in nasopharyngeal swab and
      sputum samples were examined in each patient by conventional methods and real
      time PCR, which can detect 6 bacterial and 11 viral pathogens. The causal
      association of these pathogens with AEBA severity and their frequency of monthly
      distribution were also examined. RESULTS: Among the 64 enroled patients,
      infectious pathogens were detected in 49 patients (76.6%) using real-time PCR and
      in 14 patients (21.9%) using conventional methods (p < 0.001). Real-time PCR
      detected bacteria in 29 patients (45.3%) and respiratory viruses in 28 patients
      (43.8%). Haemophilus influenzae was the most frequently detected microorganism
      (26.6%), followed by rhinovirus (15.6%). Influenza virus was the significant
      pathogen associated with severe AEBA. Moreover, AEBA occurred most frequently
      during November to January. CONCLUSIONS: Real-time PCR was more useful than
      conventional methods to detect infectious pathogens in patients with AEBA.
      Accurate detection of pathogens with real-time PCR may enable the selection of
      appropriate anti-bacterial/viral agents as a part of the treatment for AEBA.

PMID- 29166937
TI  - A putative Chondroprotective role for IL-1beta and MPO in herbal treatment of
      experimental osteoarthritis.
AB  - BACKGROUND: Herbal treatment may have a chondroprotective and therapeutic effect
      on Osteoarthritis (OA). We investigated the mechanism of action of ginger and
      curcumin rhizomes cultivated in Egypt in treatment of OA in rat model. METHODS:
      Thirty-five albino rats were intra-articularly injected with Monosodium
      Iodoacetate in the knee joint. Ginger and curcumin was orally administered at
      doses of 200 and 400 mg/kg (F200 and F400). Serum levels of cartilage oligomeric
      matrix protein (COMP), hyaluronic acid (HA), malondialdehyde (MDA),
      myeloperoxidase (MPO), Interleukin-1 beta (IL-1beta) and superoxide dismutase
      activity (SOD) were measured using ELISA. The composition of the herbal formula
      hydro-ethanolic extract was characterized using UPLC-ESI-MS. Histopathological
      changes in injected joints was examined using routine histopathology. Statistical
      analysis was performed using one-way ANOVA. RESULTS: Serum levels of COMP, HA,
      MPO, MDA, and IL-1beta were significantly decreased in F 200, F 400 and V groups
      when compared to OA group (P value <0.0001). On the other hand SOD levels were
      significantly elevated in treated groups compared to OA groups (P value <0.0001).
      CONCLUSIONS: The ginger/curcumin at 1:1 had chondroprotective effect via anti
      inflammatory and antioxidant effect in rat OA model. Further pharmacological and
      clinical studies are needed to evaluate this effect.

PMID- 29166938
TI  - A case of blunt thoracic aortic injury requiring ECMO for acute malperfusion
      before TEVAR.
AB  - BACKGROUND: Blunt thoracic aortic injury (BTAI) is associated with a high
      mortality rate and the paradigm of treating patients with BTAI currently favours
      thoracic endovascular aneurysm repair (TEVAR) if possible. In BTAI, lethal
      malperfusion caused by a pseudoaneurysm has rarely been reported. We present the
      first report of a successful case in which a pseudoaneurysm causing the
      infrequent occurrence of lethal malperfusion and subsequent acute severe
      ischaemia in the distal portion of the thoracic descending aorta was overcome by
      veno-arterial extracorporeal membrane oxygenation (VA ECMO) as a bridging therapy
      until the initiation of TEVAR. CASE PRESENTATION: An adult woman was transferred
      to our emergency room after injuries sustained by falling from height. Her vital
      signs were unstable on admission. CT examination revealed the multiple injuries:
      traumatic subarachnoid haemorrhage, severe unstable pelvic fracture, and a grade
      III injury of the thoracic aorta. We made the decision to perform TEVAR after
      external fixation and transcatheter arterial embolization (TAE) for the pelvic
      injury. During preparations for TEVAR, her lower limbs rapidly felt cold, and her
      blood lactate level and serum potassium rapidly increased. By the clinical data
      and ultrasonography and lower extremity Doppler, we diagnosed severe ischaemia in
      distal portion of the descending aorta caused by a pseudoaneurysm proximal to the
      descending thoracic aorta. Because we still had not prepared for TEVAR, we
      immediately started VA ECMO until TEVAR could begin. After the initiation of VA
      ECMO, her lactate and potassium levels could be controlled. Under VA ECMO
      support, she underwent TEVAR. After inpatient rehabilitation, she was discharged
      home without neurologic sequelae. CONCLUSIONS: VA ECMO could be an important,
      less-invasive treatment as a bridging therapy for acute severe malperfusion
      syndrome until TEVAR is initiated for BTAI.

PMID- 29166939
TI  - Acute cerebellitis in adults: a case report and review of the literature.
AB  - BACKGROUND: Acute cerebellitis is a rare disease with the majority of cases
      described in children. Little is known about the clinical characteristics and
      outcome in adults. CASE PRESENTATION: A 37-year-old Caucasian woman presented
      with headache, nausea, and photophobia, and was diagnosed as having a migraine
      attack. Two days later, she subsequently returned with aggravated headache,
      dysarthria and horizontal nystagmus. Magnetic resonance imaging (MRI) showed a
      swollen cerebellum and hydrocephalus and the patient was diagnosed with acute
      cerebellitis. Cerebrospinal fluid (CSF) examination showed an elevated leukocyte
      count and protein. Blood serology showed the presence of immunoglobulin M and
      immunoglobulin G for both Epstein-Barr virus and cytomegalovirus. The patient was
      treated with dexamethasone and discharged to a rehabilitation center, where she
      fully recovered. We searched the literature for adult cases of acute
      cerebellitis. Including our patient, we identified 35 patients with a median age
      of 36 years. The etiology was unknown in 34% of cases. The most common clinical
      presentation consisted of headache, nausea/vomiting and ataxia. Six patients
      presented with only headache and nausea and subsequently returned with cerebellar
      signs. In 9 cases, the cerebellitis was complicated by hydrocephalus. Half of the
      patients ended up with neurological sequelae, while follow-up MRI was abnormal in
      71%. CONCLUSION: Acute cerebellitis in adults is a rare disorder which mainly
      presents with headache, nausea/vomiting and ataxia. To diagnose cerebellitis,
      imaging of the brain (preferably MRI) is required and CSF examination may be
      necessary to narrow the differential diagnosis. The treatment depends on the
      widely diverse etiology, and treatment with steroids is recommended in the case
      of cerebellar oedema and hydrocephalus. Neurosurgical intervention may be
      necessary to prevent brain herniation.

PMID- 29166940
TI  - Effects of urban coarse particles inhalation on oxidative and inflammatory
      parameters in the mouse lung and colon.
AB  - BACKGROUND: Air pollution is a recognized aggravating factor for pulmonary
      diseases and has notably deleterious effects on asthma, bronchitis and pneumonia.
      Recent studies suggest that air pollution may also cause adverse effects in the
      gastrointestinal tract. Accumulating experimental evidence shows that immune
      responses in the pulmonary and intestinal mucosae are closely interrelated, and
      that gut-lung crosstalk controls pathophysiological processes such as responses
      to cigarette smoke and influenza virus infection. Our first aim was to collect
      urban coarse particulate matter (PM) and to characterize them for elemental
      content, gastric bioaccessibility, and oxidative potential; our second aim was to
      determine the short-term effects of urban coarse PM inhalation on pulmonary and
      colonic mucosae in mice, and to test the hypothesis that the well-known
      antioxidant N-acetyl-L-cysteine (NAC) reverses the effects of PM inhalation.
      RESULTS: The collected PM had classical features of urban particles and possessed
      oxidative potential partly attributable to their metal fraction. Bioaccessibility
      study confirmed the high solubility of some metals at the gastric level. Male
      mice were exposed to urban coarse PM in a ventilated inhalation chamber for 15
      days at a concentration relevant to episodic elevation peak of air pollution.
      Coarse PM inhalation induced systemic oxidative stress, recruited immune cells to
      the lung, and increased cytokine levels in the lung and colon. Concomitant oral
      administration of NAC reversed all the observed effects relative to the
      inhalation of coarse PM. CONCLUSIONS: Coarse PM-induced low-grade inflammation in
      the lung and colon is mediated by oxidative stress and deserves more
      investigation as potentiating factor for inflammatory diseases.

PMID- 29166941
TI  - Are there differences in treatment effects between labial and lingual fixed
      orthodontic appliances? A systematic review and meta-analysis.
AB  - BACKGROUND: An evaluation is made of possible differences in treatment effects
      between labial and lingual fixed appliances. METHODS: A comprehensive search was
      made of the PubMed-Medline, Cochrane Library and LILACS databases, with an
      additional manual search covering the period up until April 2017. There were no
      restrictions in terms of year of publication or language. Agreement between the
      authors was quantified by the Cohen kappa statistic. A random-effect model was
      applied to calculate weighted mean differences with 95% confidence intervals.
      RESULTS: A total of 249 patients corresponding to four eligible studies were
      included in the systematic review. Among the six angles and distances entered in
      the meta-analysis, a tendency was observed in lingual appliances to increase the
      interincisal angle (95% CI -0.80-8.99; p = 0.101) and reduce the angle between
      the major axis of upper central incisor and the sellar-nasion plane - though
      statistical significance was not reached (95% CI -5.75-0.32; p = 0.079).
      CONCLUSION: The results obtained indicate that treatment with lingual appliances
      favors incisor tipping by exerting lingual crown torque, but there are no
      differences in cephalometric values between labial and lingual fixed appliances.
      Because of the small number of included studies, the results of this meta
      analysis should be interpreted with caution. Future research should focus on the
      generation of a consensus document allowing selection of the type of orthodontic
      approach not only conditioned to the esthetic requirements of the patient but
      also considering the characteristics of the malocclusion. On the other hand,
      standardized international guidelines are lacking; the measurements of angles and
      distances therefore have to be unified with a view to future investigations.

PMID- 29166942
TI  - Postoperative radiotherapy with or without concurrent chemotherapy for oral
      squamous cell carcinoma in patients with three or more minor risk factors: a
      propensity score matching analysis.
AB  - BACKGROUND: To investigate the advantage of concurrent chemotherapy with
      postoperative radiotherapy (RT) of oral squamous cell carcinoma (OSCC) in
      patients with three or more minor risk factors. METHODS: Minor risk factors
      included pT4 disease, pN1 disease, margin <= 4 mm, poor differentiation,
      perineural invasion, vessel or lymphatic invasion, and tumor invasion depth >= 11
      mm. Surgery was the primary treatment, followed by RT or concurrent
      chemoradiation (CCRT). After propensity score matching, 34 patients in each
      treatment group were selected for comparison. RESULTS: The median follow-up for
      living patients was 86.4 months (range: 47-189 months). The 5-year overall
      survival of the RT and CCRT groups was 35.3% and 67.2% (p = 0.018), respectively.
      The 5-year recurrence-free survival of the RT group and CCRT group was 42.6% and
      75.4% (p < 0.01). CONCLUSION: Postoperative CCRT for patients with three or more
      minor risk factors increased recurrence-free and overall survival.

PMID- 29166943
TI  - High-flow nasal cannula versus noninvasive positive pressure ventilation in acute
      respiratory failure: interaction between PaO2/FiO2 and tidal volume.

PMID- 29166944
TI  - Targeting of vascular adhesion protein-1 by positron emission tomography
      visualizes sites of inflammation in Borrelia burgdorferi-infected mice.
AB  - BACKGROUND: In the present study, we sought to evaluate the feasibility of
      targeting vascular adhesion protein-1 (VAP-1) by positron emission tomography
      (PET) for the longitudinal quantitative assessment of Borrelia burgdorferi
      infection-induced inflammation in mice. METHODS: Mice with B. burgdorferi
      infection-induced arthritis were studied. During a 7-week follow-up period, the
      progression of arthritis was monitored weekly with 68Ga-DOTA-Siglec-9
      PET/computed tomography (CT) and measurement of tibiotarsal joint swellings. A
      subgroup of infected mice was treated with ceftriaxone. Finally,
      histopathological assessment of joint inflammation was performed and VAP-1
      expression in joints were determined. RESULTS: Explicit joint swelling and 68Ga
      DOTA-Siglec-9 uptake could be demonstrated in the affected joints from B.
      burgdorferi-infected mice. By contrast, no obvious accumulation of 68Ga-DOTA
      Siglec-9 was detected in joints of uninfected mice. The maximum swelling and
      highest uptake in the affected joints were observed 4 weeks after the infection.
      68Ga-DOTA-Siglec-9 uptake in joints correlated with joint swelling (P < 0.0001)
      and histopathological scoring of inflammation (P = 0.020). Despite short-term
      antibiotic treatment, the arthritis persisted, and the PET signal remained as
      high as in nontreated mice. Immunohistochemistry revealed strong-to-moderate
      expression of VAP-1 in the synovium of B. burgdorferi-infected mice, while only
      weak expression of VAP-1 was detected in uninfected mice. CONCLUSIONS: The
      present study showed that 68Ga-DOTA-Siglec-9 can detect B. burgdorferi infection
      induced arthritis in mice. Furthermore, longitudinal PET/CT imaging allowed
      monitoring of arthritis development over time.

PMID- 29166946
TI  - Noise exposure while commuting in Toronto - a study of personal and public
      transportation in Toronto.
AB  - BACKGROUND: With an increasing proportion of the population living in cities,
      mass transportation has been rapidly expanding to facilitate the demand, yet
      there is a concern that mass transit has the potential to result in excessive
      exposure to noise, and subsequently noise-induced hearing loss. METHODS: Noise
      dosimetry was used to measure time-integrated noise levels in a representative
      sample of the Toronto Mass Transit system (subway, streetcar, and buses) both
      aboard moving transit vehicles and on boarding platforms from April - August
      2016. 210 measurements were conducted with multiple measurements approximating 2
      min on platforms, 4 min within a vehicle in motion, and 10 min while in a car, on
      a bike or on foot. Descriptive statistics for each type of transportation, and
      measurement location (platform vs. vehicle) was computed, with measurement
      locations compared using 1-way analysis of variance. RESULTS: On average, there
      are 1.69 million riders per day, who are serviced by 69 subway stations, and 154
      streetcar or subway routes. Average noise level was greater in the subway and bus
      than in the streetcar (79.8 +/- 4.0 dBA, 78.1 +/- 4.9 dBA, vs 71.5 +/-1.8 dBA, p
      < 0.0001). Furthermore, average noise measured on subway platforms were higher
      than within vehicles (80.9 +/- 3.9 dBA vs 76.8 +/- 2.6 dBA, p < 0.0001). Peak
      noise exposures on subway, bus and streetcar routes had an average of 109.8 +/-
      4.9 dBA and range of 90.4-123.4 dBA, 112.3 +/- 6.0 dBA and 89.4-128.1 dBA, and
      108.6 +/- 8.1 dBA and 103.5-125.2 dBA respectively. Peak noise exposures exceeded
      115 dBA on 19.9%, 85.0%, and 20.0% of measurements in the subway, bus and
      streetcar respectively. CONCLUSIONS: Although the mean average noise levels on
      the Toronto transit system are within the recommended level of safe noise
      exposure, cumulative intermittent bursts of impulse noise (peak noise exposures)
      particularly on bus routes have the potential to place individuals at risk for
      noise induced hearing loss.

PMID- 29166945
TI  - Predictive factors of acute skin reactions to carbon ion radiotherapy for the
      treatment of malignant bone and soft tissue tumors.
AB  - BACKGROUND: The skin is considered a critical organ at risk in carbon ion
      radiotherapy (CIRT) for locally advanced malignant bone and soft tissue tumors
      (MBSTs). The predictive factors for acute skin reactions after CIRT have not been
      investigated. The present study aimed to identify these factors and evaluate the
      correlation between the severity of acute skin reactions and skin dose
      parameters. METHODS: CIRT with total doses of 64.0-70.4 Gy (relative biological
      effectiveness [RBE]) was administered to 22 patients with MBSTs. The skin-tumor
      distance (STD), maximum skin total dose (Dmax), and area of the skin receiving a
      total dose of X Gy (RBE) were evaluated. RESULTS: All patients developed acute
      skin reactions after CIRT, including Grades 1 and 2 dermatitis in 15 (71%) and 6
      (29%) patients, respectively. There was a significant difference in the STD
      between the two groups (P = 0.007), and the cut-off value of STD for predicting
      Grade 2 acute skin reactions was 11 mm. There was a significant difference in
      Dmax between the groups (P < 0.001), and the cut-off value of Dmax for predicting
      Grade 2 acute skin reactions was 52 Gy (RBE). Significant differences between the
      two groups were observed in terms of the area irradiated with 40 Gy (RBE) (S40),
      and the cut-off value of S40 for predicting Grade 2 acute skin reactions was 25
      cm2. CONCLUSIONS: In acute skin reactions after CIRT for MBSTs, STD, Dmax, and
      S40 were found to be significant predictive factors for acute skin reactions.

PMID- 29166947
TI  - A systematic literature review of evidence-based clinical practice for rare
      diseases: what are the perceived and real barriers for improving the evidence and
      how can they be overcome?
AB  - BACKGROUND: Evidence-based clinical practice is challenging in all fields, but
      poses special barriers in the field of rare diseases. The present paper
      summarises the main barriers faced by clinical research in rare diseases, and
      highlights opportunities for improvement. METHODS: Systematic literature searches
      without meta-analyses and internal European Clinical Research Infrastructure
      Network (ECRIN) communications during face-to-face meetings and telephone
      conferences from 2013 to 2017 within the context of the ECRIN Integrating
      Activity (ECRIN-IA) project. RESULTS: Barriers specific to rare diseases comprise
      the difficulty to recruit participants because of rarity, scattering of patients,
      limited knowledge on natural history of diseases, difficulties to achieve
      accurate diagnosis and identify patients in health information systems, and
      difficulties choosing clinically relevant outcomes. CONCLUSIONS: Evidence-based
      clinical practice for rare diseases should start by collecting clinical data in
      databases and registries; defining measurable patient-centred outcomes; and
      selecting appropriate study designs adapted to small study populations. Rare
      diseases constitute one of the most paradigmatic fields in which multi
      stakeholder engagement, especially from patients, is needed for success. Clinical
      research infrastructures and expertise networks offer opportunities for
      establishing evidence-based clinical practice within rare diseases.

PMID- 29166949
TI  - The 23-year tracking of blood lipids from adolescence to adulthood in Korea: the
      Kangwha study.
AB  - BACKGROUND: Several studies have examined tracking pattern of blood lipids level
      during long follow-up periods in Western countries. However, there have been few
      such studies in Asian populations. METHODS: The Kangwha Study is a community
      based prospective cohort study that started in 1986 on Kangwha Island, South
      Korea. A total of 432 participants (47% men) were enrolled in the study, during
      which serum total cholesterol, triglycerides, and high-density lipoprotein (HDL)
      cholesterol levels were measured for each participant at least once during
      adolescence (12-16 years of age) and again at least once during adulthood (25-35
      years of age). The tracking patterns of the blood lipid levels were determined
      using Spearman correlation coefficients and tracking coefficients from
      generalized estimating equations. RESULTS: The Spearman correlation coefficients
      between lipid measurements ranged from 0.12 to 0.73 depending on the lipid
      profile and measurement time interval; all were significant (p < 0.05). The
      magnitude of the coefficients tended to decrease as the time interval increased.
      When adjusted for age, sex, body mass index, and blood pressure, the tracking
      coefficients were 0.58 (95% confidence interval [CI]: 0.54-0.63) for total
      cholesterol, 0.39 (95% CI: 0.31-0.48) for triglycerides, and 0.51 (95% CI: 0.47
      0.56) for HDL cholesterol. In a subgroup analysis by sex, the tracking
      coefficients were higher for women than for men, except for HDL cholesterol.
      CONCLUSIONS: The tracking patterns of blood lipids from adolescence to adulthood
      were notable. This study supports the importance of measuring lipids during
      adolescence for identifying high-risk individuals.

PMID- 29166951
TI  - Diversity, prevalence and host specificity of avian parasites in southern
      Tunisian oases.
AB  - Oases are semi-natural woodlots surrounded by an inhospitable desert environment.
      This insular-like habitat system is known to support a mixture of sedentary and
      migratory bird species originating from different areas. However, little is known
      about the interactions between these birds and parasites. In this study, we
      investigated the diversity, prevalence and host specificity of avian
      haemosporidian parasites in southern Tunisian oases in two sedentary and common
      bird species, the laughing dove Spilopelia senegalensis and hybrid sparrow Passer
      domesticus * hispaniolensis, in six sites that differ regarding vegetation
      structure and distance to the coast. Two new Haemoproteus lineages, related to
      other Haemoproteus transmitted by biting midges, were detected in doves. With
      regard to sparrows, all detected parasites have previously been reported in other
      sparrow populations, except for one new Haemoproteus lineage. Our results also
      showed that densely vegetated sites were characterized by the higher prevalence
      of Plasmodium but a lower prevalence of Haemoproteus compared with less-vegetated
      sites. This is the first study aiming to explore avian parasites in the oasis
      habitat. Gathering data on a larger sample of oases with different sizes and
      isolation levels will be the next step to better understand factors shaping the
      transmission dynamics of avian parasites in such ecosystems.

PMID- 29166950
TI  - Global phylogenetic analysis of contemporary aleutian mink disease viruses
      (AMDVs).
AB  - BACKGROUND: Aleutian mink disease has major economic consequences on the mink
      farming industry worldwide, as it causes a disease that affects both the fur
      quality and the health and welfare of the mink. The virus causing this disease is
      a single-stranded DNA virus of the genus Amdoparvovirus belonging to the family
      of Parvoviridae. In Denmark, infection with AMDV has largely been restricted to a
      region in the northern part of the country since 2001, affecting only 5% of the
      total Danish mink farms. However, in 2015 outbreaks of AMDV were diagnosed in all
      parts of the country. Initial analyses revealed that the out breaks were caused
      by two different strains of AMDV that were significant different from the
      circulating Danish strains. To track the source of these outbreaks, a major
      investigation of global AMDV strains was initiated. METHODS: Samples from 13
      different countries were collected and partial NS1 gene was sequenced and
      subjected to phylogenetic analyses. RESULTS: The analyses revealed that AMDV
      exhibited substantial genetic diversity. No clear country wise clustering was
      evident, but exchange of viruses between countries was revealed. One of the
      Danish outbreaks was caused by a strain of AMDV that closely resembled a strain
      originating from Sweden. In contrast, we did not identify any potential source
      for the other and more widespread outbreak strain. CONCLUSION: To the authors
      knowledge this is the first major global phylogenetic study of contemporary AMDV
      partial NS1 sequences. The study proved that partial NS1 sequencing can be used
      to distinguish virus strains belonging to major clusters. The partial NS1
      sequencing can therefore be a helpful tool in combination with epidemiological
      data, in relation to outbreak tracking. However detailed information on farm to
      farm transmission requires full genome sequencing.

PMID- 29166948
TI  - Cause-specific mortality for 249 causes in Brazil and states during 1990-2015: a
      systematic analysis for the global burden of disease study 2015.
AB  - BACKGROUND: Reliable data on cause of death (COD) are fundamental for planning
      and resource allocation priorities. We used GBD 2015 estimates to examine levels
      and trends for the leading causes of death in Brazil from 1990 to 2015. METHODS:
      We describe the main analytical approaches focused on both overall and specific
      causes of death for Brazil and Brazilian states. RESULTS: There was an overall
      improvement in life expectancy at birth from 1990 to 2015, but with important
      heterogeneity among states. Reduced mortality due to diarrhea, lower respiratory
      infections, and other infectious diseases contributed the most for increasing
      life expectancy in most states from the North and Northeast regions. Reduced
      mortality due to cardiovascular diseases was the highest contributor in the
      South, Southeast, and Center West regions. However, among men, intentional
      injuries reduced life expectancy in 17 out of 27 states. Although age
      standardized rates due to ischemic heart disease (IHD) and cerebrovascular
      disease declined over time, these remained the leading CODs in the country and
      states. In contrast, leading causes of premature mortality changed substantially 
      e.g., diarrheal diseases moved from 1st to 13th and then the 36th position in
      1990, 2005, and 2015, respectively, while violence moved from 7th to 1st and to
      2nd. Overall, the total age-standardized years of life lost (YLL) rate was
      reduced from 1990 to 2015, bringing the burden of premature deaths closer to
      expected rates given the country's Socio-demographic Index (SDI). In 1990, IHD,
      stroke, diarrhea, neonatal preterm birth complications, road injury, and violence
      had ratios higher than the expected, while in 2015 only violence was higher,
      overall and in all states, according to the SDI. CONCLUSIONS: A widespread
      reduction of mortality levels occurred in Brazil from 1990 to 2015, particularly
      among children under 5 years old. Major shifts in mortality rates took place
      among communicable, maternal, neonatal, and nutritional disorders. The mortality
      profile has shifted to older ages with increases in non-communicable diseases as
      well as premature deaths due to violence. Policymakers should address health
      interventions accordingly.

PMID- 29166952
TI  - Effects of dietary live yeast supplementation on growth performance, diarrhoea
      severity, intestinal permeability and immunological parameters of weaned piglets
      challenged with enterotoxigenic Escherichia coli K88.
AB  - This study aimed to investigate the effects of dietary live yeast (LY)
      supplementation on growth, intestinal permeability and immunological parameters
      of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Piglets
      weaned at 21 d were allocated into three treatments with six pens and six piglets
      per pen, receiving the control diet (CON), diets supplemented with antibiotics
      plus zinc oxide (ANT-ZnO) and LY (Saccharomyces cerevisiae strain CNCM I-4407),
      respectively, for a period of 2 weeks. On day 8, thirty-six piglets were selected
      as control without ETEC (CON), CON-ETEC, ANT-ZnO-ETEC and LY-ETEC groups
      challenged with ETEC until day 10 for sample collections. Piglets fed ANT-ZnO
      diet had the highest average daily gain and average daily feed intake (P<0.05)
      during the 1st week, but ADG of piglets fed the ANT-ZnO diet was similar as
      piglets fed LY diet during the second week. Piglets with LY-ETEC or ANT-ZnO-ETEC
      had markedly lower diarrhoea score (P<0.05) than piglets with CON-ETEC during the
      24 h after ETEC challenge. Relative to piglets with CON, the counts of E. coli,
      urinary ratio of lactulose to mannitol, plasma IL-6 concentration, mRNA
      abundances of innate immunity-related genes in ileum and mesenteric lymph node
      tissues were increased (P<0.05), whereas the villous height of jejunum and
      relative protein expression of ileum claudin-1 were decreased (P<0.05) in piglets
      with CON-ETEC; however, these parameters did not markedly change in piglets with
      LY-ETEC or ANT-ZnO-ETEC. In summary, dietary LY supplementation could alleviate
      the severity of diarrhoea in piglets with ETEC, which may be associated with the
      improved permeability, innate immunity and bacterial profile.

PMID- 29166953
TI  - Mating system, age, and reproductive performance in Tenuisvalvae notata, a long
      lived ladybird beetle.
AB  - The long-lived polygynandrous ladybird beetle Tenuisvalvae notata (Mulsant) found
      in Brazil was evaluated in the laboratory for the effects of multiple mating and
      aging on its reproductive performance. This species is native to South America
      and is an important predator of mealybugs. Specifically studied were partner
      choice, female reproductive success, adult longevity, male virility, and
      offspring development. Young (5-10 days old) and older virgin females (95-100
      days old) were subjected to either a single mate or multiple mating with the same
      or different males of various mating status (virgin or previously mated once,
      twice, and thrice). Results revealed a preference in both genders to mate with
      previously known partners. Additionally, younger females had higher fecundity and
      greater longevity when mated only once in comparison to those mated multiple
      times. Fecundity, fertility, and offspring development were similar across the
      treatments regardless of the number of mating or male mating history. Fecundity
      and fertility decreased throughout the oviposition period regardless of mating
      treatment.

PMID- 29166954
TI  - State-of-the-art for food taxes to promote public health.
AB  - The use of taxes to promote healthy nutritional behaviour has gained ground in
      the past decade. The present paper reviews existing applications of fiscal
      instruments in nutrition policy and derives some perspectives and recommendations
      from the experiences gained with these instruments. Many countries in different
      parts of the world have experiences with the taxation of sugar-sweetened
      beverages, in some cases in combination with taxes on unhealthy food commodities
      such as confectionery or high-fat foods. These tax schemes have many
      similarities, but also differ in their definitions of tax objects and in the
      applied tax rates. Denmark has been the only country in the world to operate a
      tax on saturated fat content in foods, from 2011 to 2012. Most of the existing
      food tax schemes have been introduced from fiscal motivations, with health
      promotion as a secondary objective, but a few have been introduced with health
      promotion as the primary objective. The diversity in experiences from existing
      tax schemes can provide valuable insights for future use of fiscal instruments to
      promote healthy nutrition, in terms of designing effective and efficient tax or
      subsidy instruments, and in terms of smooth and politically viable implementation
      of the instruments.

PMID- 29166956
TI  - Systematic review of infant and young child complementary feeding practices in
      South Asian families: the India perspective.
AB  - OBJECTIVE: Suboptimal nutrition among children remains a problem among South
      Asian (SA) families. Appropriate complementary feeding (CF) practices can greatly
      reduce this risk. Thus, we undertook a systematic review of studies assessing CF
      (timing, dietary diversity, meal frequency and influencing factors) in children
      aged <2 years in India. DESIGN: Searches between January 2000 and June 2016 in
      MEDLINE, EMBASE, Global Health, Web of Science, OVID Maternity & Infant Care,
      CINAHL, Cochrane Library, BanglaJOL, POPLINE and WHO Global Health Library.
      Eligibility criteria: primary research on CF practices in SA children aged 0-2
      years and/or their families. Search terms: 'children', 'feeding' and 'Asians' and
      derivatives. Two researchers undertook study selection, data extraction and
      quality appraisal (EPPI-Centre Weight of Evidence). RESULTS: From 45 712
      abstracts screened, sixty-four cross-sectional, seven cohort, one qualitative and
      one case-control studies were included. Despite adopting the WHO Infant and Young
      Child Feeding guidelines, suboptimal CF practices were found in all studies. In
      twenty-nine of fifty-nine studies, CF was introduced between 6 and 9 months, with
      eight studies finding minimum dietary diversity was achieved in 6-33 %, and ten
      of seventeen studies noting minimum meal frequency in only 25-50 % of the study
      populations. Influencing factors included cultural influences, poor knowledge on
      appropriate CF practices and parental educational status. CONCLUSIONS: This is
      the first systematic review to evaluate CF practices in SA in India. Campaigns to
      change health and nutrition behaviour and revision of nationwide child health
      nutrition programmes are needed to meet the substantial unmet needs of these
      children.

PMID- 29166957
TI  - DHA supplementation during pregnancy as phospholipids or TAG produces different
      placental uptake but similar fetal brain accretion in neonatal piglets.
AB  - The great variety of n-3 long-chain PUFA sources raises the question of the most
      adequate for using as a DHA supplement during pregnancy. Placental and fetal
      availability of different DHA sources remains unclear. We investigated DHA
      availability in maternal lipoproteins, placenta and fetal tissues in pregnant
      sows fed DHA as phospholipid (PL) or TAG to identify the best DHA source during
      this period. Pregnant Iberian sows were fed diets containing 0.8 % DHA of total
      fatty acids as PL from egg yolk or TAG from algae oil during the last third of
      gestation (40 d). Maternal tissues, placentas and fetal tissues were obtained at
      delivery and DHA quantified by GC. Major Facilitator Superfamily Domain
      Containing 2a (MFSD2a) carrier expression was analysed in both placenta and fetal
      brain by Western blotting. Sows fed the DHA-PL diet showed higher DHA
      incorporation in plasma LDL but not in plasma total lipids. No differences were
      found in DHA content between groups in maternal liver, adipose tissue or brain.
      Placental tissue incorporated more DHA in both total lipids and PL fraction in
      sows fed DHA-PL. However, this did not lead to an enhanced DHA accretion either
      in fetal plasma, fetal liver or fetal brain. MFSD2a expression was similar
      between both experimental groups. Maternal DHA supplementation during pregnancy
      in sow either as PL or TAG produces similar DHA accretion in fetal tissues but
      not in placenta. Both fat sources are equally available for fetal brain.

PMID- 29166955
TI  - Brain Arterial Diameters and Cognitive Performance: The Northern Manhattan Study.
AB  - OBJECTIVES: To test the hypothesis that brain arterial diameters are associated
      with cognitive performance, particularly in arteries supplying domain-specific
      territories. METHODS: Stroke-free participants in the Northern Manhattan Study
      were invited to have a brain MRI from 2003-2008. The luminal diameters of 13
      intracranial arterial segments were obtained using time-of-flight magnetic
      resonance angiogram (MRA), and then averaged and normalized into a global score
      and region-specific arterial diameters. Z-Scores for executive function, semantic
      memory, episodic memory and processing speed were obtained at MRI and during
      follow-up. Adjusted generalized additive models were used to assess for
      associations. RESULTS: Among the 1034 participants with neurocognitive testing
      and brain MRI, there were non-linear relationships between left anterior (ACA)
      and middle cerebral artery (MCA) diameter and semantic memory Z-scores
      (chi2=10.00; DF=3; p=.019), and left posterior cerebral artery (PCA) and
      posterior communicating artery (Pcomm) mean diameter and episodic memory Z-scores
      (chi2=9.88; DF=3; p=.020). Among the 745 participants who returned for 2nd
      neuropsychological testing, on average 5.0+/-0.4 years after their MRI, semantic
      memory change was associated non-linearly with the left PCA/Pcomm mean diameter
      (chi2=13.09; DF=3; p=.004) and with the right MCA/ACA mean diameter (chi2=8.43;
      DF=3; p=.03). In both cross-sectional and longitudinal analyses, participants
      with the larger brain arterial diameters had more consistently lower Z-scores and
      greater decline than the rest of the participants. CONCLUSIONS: Brain arterial
      diameters may have downstream effects in brain function presenting as poorer
      cognition. Identifying the mechanisms and the directionality of such interactions
      may increase the understanding of the vascular contribution to cognitive
      impairment and dementia. (JINS, 2018, 24, 335-346).

PMID- 29166958
TI  - Insights into the factors associated with achieving the preference of home death
      in terminal cancer: A national population-based study.
AB  - OBJECTIVES: Most terminally ill cancer patients prefer to die at home, yet only a
      minority are able to achieve this. Our aim was to investigate the factors
      associated with cancer patients achieving their preference to die at home.
      METHODS: This study took the form of a mortality followback, population-based,
      observational survey of the relatives of deceased cancer patients in Northern
      Ireland. Individuals who registered the death of a friend or relative (aged >= 18
      years) between 1 December 2011 and 31 May 2012, where the primary cause of death
      was cancer (ICD10: C00-D48), who were invited to take part. Preferred and actual
      place of death, and patient, service, and clinical data were collected using the
      QUALYCARE postal questionnaire. Multivariable logistic regression was employed to
      investigate the factors associated with achieving a home death when preferred.
      RESULTS: Some 467 of 1,493 invited informants completed the survey. The 362
      (77.5%) who expressed a preference for dying at home and spent time at home in
      their final 3 months were included in our analysis. Of these, 53.4% achieved
      their preference of a home death. Factors positively associated with achieving a
      home death were: living in an affluent area, receipt of good and satisfactory
      district nurse care, discussing place of death with health professionals, and the
      caregiver's preference for a home death. Being older than 80 years of age, being
      a Presbyterian, and being unconscious most of the time during their final week
      were negatively associated with achieving a home death. SIGNIFICANCE OF RESULTS:
      Communication, care satisfaction, and caregiver preferences were all associated
      with home death. Our findings will help inform the design of future interventions
      aimed at increasing the proportion of patients achieving their preferred place of
      death at home, for example, by targeting interventions toward older patients and
      those from the most deprived communities.

PMID- 29166959
TI  - Short-distance dispersal of Hypothenemus hampei (Ferrari) females (Coleoptera:
      Curculionidae: Scolytidae) during the coffee tree fruiting period.
AB  - The coffee berry borer (CBB), Hypothenemus hampei (Ferrari), is a multivoltine
      species closely associated with coffee crops worldwide, causing severe damage to
      the bean. In Mexico, as in all tropical regions, CBB survives during the inter
      harvest period in residual berries on the ground or in dry berries remaining on
      the branches, and then disperses in search of the first suitable berries. In this
      study, we investigated how CBB dispersed from the first infested nodes during the
      fruiting period of Coffea canephora Pierre, which provides a favourable trophic
      level for this insect. Forty-five branches equally distributed in 15 coffee
      trees, with one infested node and four uninfested nodes, were selected. The
      branches were subjected to three treatments over nine weeks: 1) glue between
      nodes with full protection, 2) glue between nodes without protection, and 3) no
      glue and no protection. In addition, 45 CBB-free branches were selected and
      subjected to the same three treatments. CBB colonization can occur in three ways:
      1) from an infested node to an uninfested node on the same branch, 2) from
      infested berries to uninfested berries within the nodes, 3) from branches to
      other branches. We also found that CBB dispersal between nodes of the same
      branches never occurred by walking but by flying. Thus, in this context of coffee
      berry development and ripening, and unlike the phenological situation of the
      inter-harvest period, CBB continuously travels very short distances, thus
      limiting its control.

PMID- 29166960
TI  - A focussed single-view hand-held echocardiography protocol for the detection of
      rheumatic heart disease - CORRIGENDUM.

PMID- 29166961
TI  - Antibiotic resistance trends and mechanisms in the foodborne pathogen,
      Campylobacter.
AB  - Campylobacter is a major foodborne pathogen and is commonly present in food
      producing animals. This pathogenic organism is highly adaptable and has become
      increasingly resistant to various antibiotics. Recently, both the Centers for
      Disease Control and Prevention and the World Health Organization have designated
      antibiotic-resistant Campylobacter as a serious threat to public health. For the
      past decade, multiple mechanisms conferring resistance to clinically important
      antibiotics have been described in Campylobacter, and new resistance mechanisms
      constantly emerge in the pathogen. Some of the recent examples include the erm(B)
      gene conferring macrolide resistance, the cfr(C) genes mediating resistance to
      florfenicol and other antimicrobials, and a functionally enhanced variant of the
      multidrug resistance efflux pump, CmeABC. The continued emergence of new
      resistance mechanisms illustrates the extraordinary adaptability of Campylobacter
      to antibiotic selection pressure and demonstrate the need for innovative
      strategies to control antibiotic-resistant Campylobacter. In this review, we will
      briefly summarize the trends of antibiotic resistance in Campylobacter and
      discuss the mechanisms of resistance to antibiotics used for animal production
      and important for clinical therapy in humans. A special emphasis will be given to
      the newly discovered antibiotic resistance.

PMID- 29166962
TI  - Biology of two larval morphological phenotypes of Aedes aegypti in Abidjan, Cote
      d'Ivoire.
AB  - Since 2008, several outbreaks of yellow fever and dengue occurred in Abidjan, the
      economic capital of Cote d'Ivoire. A better knowledge of the biology of Aedes
      aegypti populations, the main vector of yellow fever and dengue viruses, is
      necessary to tailor vector control strategies implemented in the city. This study
      was designed to determine some biological parameters, occurring during the life
      cycle of two morphological phenotypes of Ae. aegypti larvae. Mosquitoes were
      sampled in a suburb of Abidjan (Treichville) using the WHO layer-traps technique.
      Biological parameters were studied in laboratory under standard conditions of
      temperature (27 degrees C +/- 2 degrees C) and relative humidity (80% +/- 10%).
      Our results indicated that the mean eggs laid by females from 'brown larvae' (BL)
      (85.95, 95% confidence interval (CI 95%) 78.87-93.02) was higher than those from
      'white larvae' (WL) (64.40%, CI 95% 55.27-73.54). The gonotrophic cycle was 3 and
      4 days in females from BL and WL, respectively. The overall yield of breeding
      mosquitoes from BL (63.88%, CI 95% 62.61-65.14) was higher compared with those of
      mosquitoes from WL (59.73%, CI 95% 58.35-61.12). The sex ratio (male/female) was
      0.95 and 1.68 in Ae. aegypti populations from BL and WL, respectively. Females
      from BL lived slightly longer than those from WL (t = -2.332; P = 0.021). This
      study shows that Ae. Aegypti populations from BL and WL present different
      biological parameters during their life cycle. This could have an implication on
      their ability to transmit human disease viruses such as dengue and yellow fever.
      Further molecular studies are needed to determine genetic divergence between
      these Ae. aegypti populations.

PMID- 29166963
TI  - Anatomical, morphological, and physiological responses of two sugarcane genotypes
      of contrasting susceptibility to Mahanarva fimbriolata (Hemiptera: Cercopidae).
AB  - The purpose of this study was to investigate and compare root morpho-anatomical
      traits and physiological responses of susceptible (SP81-3250) and resistant (H.
      Kawandang) sugarcane genotypes exposed to the attack by nymphs of spittlebug
      Mahanarva fimbriolata (Stal) (Hemiptera: Cercopidae). Two experiments were
      conducted to compare the damage caused by spittlebug nymphs on fresh and dry
      biomass weight; lignin content in stalks; root anatomy; chlorophyll content;
      photosynthetic rate (A); carboxylation efficiency (A/Ci); stomatal conductance
      (gS) and transpiration rate (E) of these genotypes. SP81-3250 consistently
      obtained significantly higher damage scores than H. Kawandang in both
      experiments, confirming the previously observed level of resistance in each
      genotype. Attack by spittlebug nymphs had a much higher effect on both fresh and
      dry biomass weight, chlorophyll content, A, A/Ci, gs and E of SP81-3250, than
      that on H. Kawandang. Anatomical studies indicated the presence of aerenchyma
      tissue in the root cortex of SP81-3250, a feature which may facilitate
      penetration of the nymph's stylet into the vascular cylinder. In contrast, roots
      of H. Kawandang are characterized by having more dense and compact parenchyma
      cells. In addition, infested plants of this genotype contained an unidentified
      mucilaginous compound in the vascular cylinder of the roots. We conclude that
      resistance of H. Kawandang to spittlebug is related to the ability of this
      genotype to maintain normal chlorophyll content, as well as stomatal conductance
      and photosynthesis, thus, allowing for biomass accumulation under spittlebug
      attack, in contrast to SP81-3250. In addition, the presence of more compact and
      denser parenchymal cells, as well as that of an induced mucilaginous compound in
      the root's vascular cylinder, are likely to hinder host-feeding activity in
      nymphs, causing higher nymph mortality and therefore, reduced damage in plants of
      this genotype.

PMID- 29166964
TI  - How do childhood intelligence and early psychosocial adversity influence income
      attainment among adult extremely low birth weight survivors? A test of the
      cognitive reserve hypothesis.
AB  - Perinatal and later postnatal adversities have been shown to adversely affect
      socioeconomic trajectories, while enhanced early cognitive abilities improve
      them. However, little is known about the combined influence of these exposures on
      social mobility. In this study, we examined if childhood IQ moderated the
      association between four different types of postnatal adversity (childhood
      socioeconomic disadvantage, childhood sexual abuse, lifetime psychiatric
      disorder, and trait neuroticism) and annual earnings at 30-35 years of age in a
      sample of 88 extremely low birth weight survivors. Our results suggested that
      higher childhood IQ was associated with greater personal income at age 30-35.
      Extremely low birth weight survivors who did not face psychological adversities
      and who had higher childhood IQ reported higher income in adulthood. However,
      those who faced psychological adversity and had higher childhood IQ generally
      reported lower income in adulthood. Our findings suggest that cognitive reserve
      may not protect preterm survivors against the complex web of risk factors
      affecting their later socioeconomic attainment.

PMID- 29166965
TI  - Environmental determinants of haemosporidian parasite prevalence in a declining
      population of Tree swallows.
AB  - The prevalence of vector-borne parasites such as haemosporidian species is
      influenced by several environmental factors. While the negative effects of
      parasitism on hosts are well documented, these can also be amplified by
      interactions with environmental stressors, many of which are anthropogenic. Yet,
      we know little about the possible effects of anthropogenic perturbations on
      parasite prevalence. The goals of this study were to assess the prevalence and
      environmental determinants of haemosporidian parasites in a declining population
      of Tree swallows (Tachycineta bicolor) living in an agricultural landscape in
      southern Quebec, Canada. Overall, a low prevalence and a moderate lineage
      diversity were identified in both adults and nestlings, confirming that
      transmission can occur during the breeding period. Anthropic areas, extensive
      cultures (hayfields and pastures) and forest cover within 500 km of nest boxes,
      as well as daily temperature fluctuations, were all related to infection by
      haemosporidian parasites. These findings suggest that anthropogenic alterations
      of landscape composition can modulate the prevalence of haemosporidian parasites
      in Tree swallows. Our results represent a baseline for future comparative studies
      assessing haemosporidian parasite prevalence in human-modified landscapes.

PMID- 29166966
TI  - The feeding system impacts relationships between calving interval and economic
      results of dairy farms.
AB  - The calving interval (CI) can potentially impact the economic results of dairy
      farms. This study highlighted the most profitable CI and innovated by describing
      this optimum as a function of the feeding system of the farm. On-farm data were
      used to represent real farm conditions. A total of 1832 accounts of farms
      recorded from 2007 to 2014 provided economic, technical and feeding information
      per herd and per year. A multiple correspondence analysis created four feeding
      groups: extensive, low intensive, intensive and very intensive herds. The gross
      margin and some of its components were corrected to account for the effect of
      factors external to the farm, such as the market, biological status, etc. Then
      the corrected gross margin (cGMc) and its components were modelled by CI
      parameters in each feeding system by use of GLM. The relationship between cGMc
      and the proportion of cows with CI<380 days in each feeding group showed that
      keeping most of the cows in the herd with CI near to 1 year was not profitable
      for most farms (for the very intensive farms there was no effect of the
      proportion). Moreover, a low proportion of cows (0% to 20%) with a near-to-1-year
      CI was not profitable for the extensive and low intensive farms. Extending the
      proportion of cows with CI beyond 459 days until 635 days (i.e. data limitation)
      caused no significant economic loss for the extensive and low intensive farms,
      but was not profitable for the intensive and very intensive farms. Variations of
      the milk and feeding components explained mainly these significant differences of
      gross margin. A link between the feeding system and persistency, perceptible in
      the milk production and CI shown by the herd, could explain the different
      relationships observed between the extent of CI and the economic results in the
      feeding groups. This herd-level study tended to show different economic optima of
      CI as a function of the feeding system. A cow-level study would specify these
      tendencies to give CI objectives to dairy breeders as a function of their farm
      characteristics.

PMID- 29166967
TI  - The clinical significance of drug-placebo differences.

PMID- 29166968
TI  - Infant feeding practices and dietary consumption of US infants and toddlers:
      National Health and Nutrition Examination Survey (NHANES) 2003-2012.
AB  - OBJECTIVE: To compare infant and toddler anthropometric measurements, feeding
      practices and mean nutrient intakes by race/ethnicity and income. DESIGN: Cross
      sectional analysis using general linear modelling. Ten years of survey data (2003
      2012) were combined to compare anthropometric measurements, feeding practices and
      mean nutrient intakes from a nationally representative US sample. SETTING: The
      2003-2012 National Health and Nutrition Examination Survey (NHANES). SUBJECTS:
      Infants and toddlers (n 3669) aged 0-24 months. RESULTS: Rates of overweight were
      higher among Mexican-American infants and toddlers (P=0.002). There were also
      several differences in feeding practices among groups based on race/ethnicity.
      Cessation of breast-feeding occurred earlier for non-Hispanic black and Mexican
      American v. non-Hispanic white infants (3.6 and 4.2 v. 5.3 months; P<0.0001;
      P=0.001). Age at first feeding of solids was earlier for white than Mexican
      American infants (5.3 v. 5.7 months; P=0.02). There were differences in almost
      all feeding practices based on income, including the lowest-income infants
      stopped breast-feeding earlier than the highest-income infants (3.2 v. 5.8
      months, P<0.0001). Several differences in mean nutrient intakes by both
      race/ethnicity and income were also identified. CONCLUSIONS: Our study indicates
      that disparities in overweight, feeding practices and mean nutrient intakes exist
      among infants and toddlers according to race/ethnicity, which cannot be
      disentangled from income.

PMID- 29166969
TI  - HOW TO AVOID GIVING THE RIGHT ANSWERS TO THE WRONG QUESTIONS: THE NEED FOR
      INTEGRATED ASSESSMENTS OF COMPLEX HEALTH TECHNOLOGIES.
AB  - Health technologies are becoming increasingly complex and contemporary health
      technology assessment (HTA) is only partly equipped to address this complexity.
      The project "Integrated assessments of complex health technologies" (INTEGRATE
      HTA), funded by the European Commission, was initiated with the overall objective
      to develop concepts and methods to enable patient-centered, integrated
      assessments of the effectiveness, and the economic, social, cultural, and ethical
      issues of complex technologies that take context and implementation issues into
      account. The project resulted in a series of guidances that should support the
      work of HTA scientists and decision makers alike.

PMID- 29166970
TI  - The role of low-calorie sweeteners in the prevention and management of overweight
      and obesity: evidence v. conjecture.
AB  - By virtue of reducing dietary energy density, low-calorie sweeteners (LCS) can be
      expected to decrease overall energy intake and thereby decrease body weight. Such
      effects will be limited by the amount of sugar replaced by LCS, and the dynamics
      of appetite and weight control (e.g., acute compensatory eating, and an increase
      in appetite and decrease in energy expenditure accompanying weight loss).
      Consistent with these predictions, short-term intervention studies show
      incomplete compensation for the consumption of LCS v. sugar, and longer-term
      intervention studies (from 4 weeks to 40 months duration) show small decreases in
      energy intake and body weight with LCS v. sugar. Despite this evidence, there are
      claims that LCS undermine weight management. Three claims are that: (1) LCS
      disrupt the learned control of energy intake (sweet taste confusion hypothesis);
      (2) exposure to sweetness increases desire for sweetness (sweet tooth
      hypothesis); (3) consumers might consciously overcompensate for 'calories saved'
      when they know they are consuming LCS (conscious overcompensation hypothesis).
      None of these claims stands up to close examination. In any case, the results of
      the intervention studies comparing LCS v. sugar indicate that the effect of
      energy dilution outweighs any tendency LCS might conceivably have to increase
      energy intake.

PMID- 29166971
TI  - A review on metronidazole: an old warhorse in antimicrobial chemotherapy.
AB  - The 5-nitroimidazole drug metronidazole has remained the drug of choice in the
      treatment of anaerobic infections, parasitic as well as bacterial, ever since its
      development in 1959. In contrast to most other antimicrobials, it has a
      pleiotropic mode of action and reacts with a large number of molecules.
      Importantly, metronidazole, which is strictly speaking a prodrug, needs to be
      reduced at its nitro group in order to become toxic. Reduction of metronidazole,
      however, only takes place under very low concentrations of oxygen, explaining why
      metronidazole is exclusively toxic to microaerophilic and anaerobic
      microorganisms. In general, resistance rates amongst the pathogens treated with
      metronidazole have remained low until the present day. Nevertheless,
      metronidazole resistance does occur, and for the treatment of some pathogens,
      especially Helicobacter pylori, metronidazole has become almost useless in some
      parts of the world. This review will give an account on the current status of
      research on metronidazole's mode of action, metronidazole resistance in
      eukaryotes and prokaryotes, and on other 5-nitroimidazoles in use.

PMID- 29166972
TI  - Long-term sex-differential effects of neonatal vitamin A supplementation on in
      vitro cytokine responses.
AB  - High-dose vitamin A supplementation (VAS) may affect mortality to infectious
      diseases in a sex-differential manner. Here, we analysed the long-term
      immunological effects of neonatal vitamin A supplementation (NVAS) in 247
      children, who had been randomly allocated to 50 000 or 25 000 IU vitamin A (15mg
      and 7.5mg retinol equivalents, respectively) or placebo at birth. At 4-6 months
      of age, we assessed bacille Calmette-Guerin (BCG) scarification, and we analysed
      in vitro responses of TNF-alpha, IL-5, IL-10, IL-13 and IFN-gamma in whole blood
      stimulations to phytohaemagglutinin (PHA), purified protein derivative (PPD),
      tetanus toxoid and lipopolysaccharide. There were no differences between the two
      doses of NVAS, and thus they were analysed combined as NVAS (any dose) v.
      placebo. All analyses were performed unstratified and by sex. NVAS increased the
      chance of having a scar after BCG vaccination in females (NVAS v. placebo: 96 v.
      71 %, proportion ratio: 1.24; 95 % CI 1.09, 1.42), but not in males (P for
      interaction=0.012). NVAS was associated with significant sex-differential effects
      on the pro- to anti-inflammatory cytokine ratios (TNF-alpha:IL-10) to PPD,
      tetanus toxoid and medium alone, which were increased in females but decreased in
      males. In addition, IL-17 responses tended to be increased in NVAS v. placebo
      recipients in males but not in females, significantly so for the PHA stimulation.
      The study corroborates sex-differential effects of VAS on the immune system,
      emphasising the importance of analysing VAS effects by sex.

PMID- 29166973
TI  - Effectiveness of a Behavioral Approach to Improve Healthcare Worker Compliance
      With Hospital Dress Code.
AB  - BACKGROUND The VU University Medical Center, a tertiary-care hospital in the
      Netherlands, has adopted a dress code based on national guidelines. It includes
      uniforms provided by the hospital and a 'bare-below-the-elbow' policy for all
      healthcare workers (HCWs) in direct patient care. Because compliance was poor, we
      sought to improve adherence by interventions targeted at the main causes of
      noncompliance. OBJECTIVE To measure compliance with the dress code, to assess
      causes of noncompliance and to assess whether a behavioral approach (combing a
      nominal group technique with participatory action) is effective in improving
      compliance METHODS Between March 2014 and June 2016, a total of 1,920 HCWs were
      observed in hospital hallways for adherence to the policy, at baseline, and at
      follow-up measurements. Based on the outcome of the baseline measurement, a
      nominal group technique was applied to assess causes of noncompliance. The causes
      revealed served as input for interventions that were developed, prioritized, and
      tailored to specific groups of HCWs and specific departments through
      participatory action. RESULTS We identified lack of knowledge, lack of
      facilities, and negative attitudes as the main causes of noncompliance. The
      importance of each cause varied for different groups of HCWs. Tailored
      interventions targeted at these causes increased overall compliance by 39.6% (95%
      CI, 31.7-47.5). CONCLUSION The combination of a nominal group technique and
      participatory action approach is an effective method to increase and sustain
      compliance with hospital dress code. This combined approach may also be useful to
      improve adherence to other guidelines. Infect Control Hosp Epidemiol 2017;38:1435
      1440.

PMID- 29166974
TI  - A first qualitative snapshot: cardiac surgery and recovery in 10 children in the
      Red Cross War Memorial Children's Hospital, Cape Town, South Africa (2011-2016).
AB  - This article describes our qualitative research on the follow-up of 10 children,
      5 years into recovery after cardiac surgery. The research was driven by a multi
      disciplinary team of medical anthropologists, cardiologists, and an intensive
      care specialist and was based at the Red Cross War Memorial Children's Hospital
      where they underwent surgeries. The research sought to answer two questions;
      first, could we successfully maintain contact with and follow up the children;
      the second - which will be answered in future papers - asked what life was like
      for them and their families during surgery and later recovery. The results are
      presented as a discussion on the themes that arose in our engagement and analysis
      and not as clinical evidence. These showed that elective surgery although
      significantly delayed was successful, and all children were followed up at their
      medical appointments. The researchers, however, were unable to establish follow
      up with all families over the duration of the study. In the final round of
      interviews in the respondents' homes, of 10 children, we remained in contact with
      seven. The discussion argues that effective communication and access to these
      children was often compromised by their coming from the poorer communities in the
      Cape Town metropolitan region, making them even more vulnerable during their
      recovery periods.

PMID- 29166975
TI  - In vitro and in vivo efficacy of diamidines against Trypanosoma equiperdum
      strains.
AB  - Trypanosoma equiperdum is a protozoan parasite responsible for causing Dourine, a
      debilitating neglected veterinary disease, found worldwide affecting equids. It
      is the only pathogenic trypanosome species that does not require an invertebrate
      vector for transmission, thus being passed from animal to animal via coitus. At
      present, there is no officially recognized form of chemotherapeutic treatment and
      therefore all confirmed (or suspected) cases of infected animals must be
      slaughtered immediately. For many global communities and farming populations,
      which rely heavily on their animals for their livelihood, such stringent
      regulations can seriously enhance the socio-economic problems attributing to
      poverty. Two reference drugs, together with 37 novel diamidine compounds were
      tested in vitro using a 72 h drug sensitivity assay to determine their efficacy
      against two axenically adapted T. equiperdum strains. Further in vivo
      investigations in mouse models of infection against 4 'true' T. equiperdum
      strains were performed using the 17 most active diamidines. Single bolus doses of
      10 mg kg-1, given i.p. were administered to NMRI mice infected with one of the 4
      T. equiperdum strains. The results obtained from this study show that
      experimentally T. equiperdum can indeed be effectively treated with chemotherapy
      using in vivo mouse models of infection.

PMID- 29166976
TI  - Clinical, laboratory and epidemiological aspects of HPV infection in a low-income
      population from South Bahia, Brazil.
AB  - The aim of this study was to determine the prevalence and risk factors for human
      papillomavirus (HPV) infection in the Southern region of the State of Bahia,
      evaluating the performance of alternative complementary methods for cervical
      lesion detection. Cervical samples from women who attended healthcare units were
      collected and diagnosed by visual inspection, cervical cytology and nested
      polymerase chain reaction (PCR). Moreover, hemi-nested PCR was performed to
      detect different HPV genotypes. The prevalence of HPV infection was 47.7%, with
      genotype 16 detected in most cases. Infection was associated with dyspareunia and
      bleeding (P < 0.001, odds ratio (OR) 5.6, 95% confidence interval (CI) 2.815
      11.14) and hormonal contraceptive use (P = 0.007, OR 2.33, 95% CI 1.25-4.34).
      There was a positive correlation between positive PCR and positive visual
      inspection, cervical cytology and symptoms reported. Furthermore, visual
      inspection was twice as specific, and had a greater positive predictive value
      than cytology. We showed a high prevalence of HPV infection in Southern Bahia,
      with HPV 16 being the most common type, and visual inspection being most
      effective at detecting HPV lesions, corroborating the suggestion that it can be
      applied in routine gynecologic examinations for low-income populations.

PMID- 29166977
TI  - Analysis of pre-weaning feeding policies and other risk factors influencing
      growth rates in calves on 11 commercial dairy farms.
AB  - Growth rates in pre-weaned calves influence their health, age at first calving
      and lifetime productivity. Many farms restrict milk rations to encourage solid
      feed intake and facilitate early weaning, but this can compromise growth. This
      study determined the milk feeding policies and associated growth rates on 11
      commercial dairy farms in South East England, each following their normal
      management regime. Between 26 and 54 heifers were recruited per farm, providing a
      final cohort of 492, of which 71% were pure Holstein. Information on calf rearing
      practices (feeding, weaning, housing) and health was collected via questionnaires
      and weekly observations. Estimates of actual milk fed (kg solids) between 1 and
      63 days were calculated for individual calves. Morphometric data (weight, height,
      length) were taken at weeks 1, 5 and 9 and at a median age of 7.5 months and
      growth rates were calculated. Most calves were fed milk replacer via automated
      feeders (four farms), teat feeder (one) or buckets (four) whereas two farms
      provided drums of acidified waste milk. Farms fed between 4 and 6 l/day of milk
      at mixing rates of 10% to 15%, providing 400 to 900 g/day of milk solids. Both
      skeletal growth rates and average daily weight gain (ADG) increased in the second
      month of life compared with the first: height growth from 0.17+/-0.14 to 0.25+/
      0.16 cm/day and ADG from 0.48+/-0.25 to 0.71+/-0.28 kg/day. Post-weaning heifers
      up to 7.5 months had height increases of 0.16+/-0.035 cm/day and ADG of 0.83+/
      0.16 kg/day. From 1 to 63 days 70% of calves had growth rates <0.7 kg/day and of
      these 19.6% gained <0.5 kg/day. Mean ADG before 9 weeks varied between farms from
      0.52+/-0.30 to 0.75+/-0.20 kg/day. This was related to the amount of milk fed at
      both a farm and individual calf level. Increasing the total milk solids fed
      between 1 and 63 days from 20.4 to 46.3 kg (the 10th to 90th percentile observed)
      was associated with an increase of 0.11 kg/day ADG. All farms had a wide
      variation in growth rates despite single feeding policies. Higher circulating
      immunoglobulin G and IGF1 concentrations were associated with better growth,
      whereas low temperatures in month of birth, high scores for diarrhoea,
      respiratory and umbilical disease and large birth size reduced growth. Many
      commercially grown dairy heifers therefore experienced growth restriction in the
      pre-weaned period, potentially reducing their health, welfare and productivity.

PMID- 29166978
TI  - Molecular detection of influenza A(H1N1)pdm09 viruses with M genes from human
      pandemic strains among Nigerian pigs, 2013-2015: implications and associated risk
      factors.
AB  - In the post-pandemic period, influenza A(H1N1)pdm09 virus has been detected in
      swine populations in different parts of the world. This study was conducted to
      determine the presence and spatial patterns of this human pandemic virus among
      Nigerian pigs and identify associated risk factors. Using a two-stage stratified
      random sampling method, nasal swab specimens were obtained from pigs in Ibadan,
      Nigeria during the 2013-2014 and 2014-2015 influenza seasons, and the virus was
      detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Purified RT
      PCR products were sequenced in both directions, and sequences were aligned using
      MUSCLE. Phylogenetic analysis was conducted in MEGA6. Purely spatial scan
      statistics and a spatial lag regression model were used to identify spatial
      clusters and associated risk factors. The virus was detected in both seasons,
      with an overall prevalence of 8.7%. Phylogenetic analyses revealed that the M
      genes were similar to those of pandemic strains which circulated in humans prior
      to and during the study. Cluster analysis revealed a significant primary spatial
      cluster (RR = 4.71, LLR = 5.66, P = 0.0046), while 'hours spent with pigs (R 2 =
      0.90, P = 0.0018)' and 'hours spent with pigs from different farms (R 2 = 0.91, P
      = 0.0001)' were identified as significant risk factors (P < 0.05). These findings
      reveal that there is considerable risk of transmission of the pandemic virus,
      either directly from pig handlers or through fomites, to swine herds in Ibadan,
      Nigeria. Active circulation of the virus among Nigerian pigs could enhance its
      reassortment with endemic swine influenza viruses. Campaigns for adoption of
      biosecurity measures in West African piggeries and abattoirs should be introduced
      and sustained in order to prevent the emergence of a new influenza epicentre in
      the sub-region.

PMID- 29166979
TI  - Explaining variations in the diversity of parasitoid assemblages in a biosphere
      reserve of Mexico: evidence from vegetation, land management and seasonality.
AB  - Insect fauna biodiversity in natural protected areas has not been thoroughly
      studied. Therefore, the aim of this work was to assess whether and how vegetation
      types, land management and seasonality influence the diversity of Ichneumonidae
      (Hymenoptera) in the Ria Lagartos Biosphere Reserve (Mexico). A sampling
      programme was conducted using Malaise traps from 2008 to 2009 in three vegetation
      types, each with two conservation zones (core and buffer zones). Three seasons
      were considered: rainy, dry and north-winds (isolated storms from November to
      February). A total of 336 species were identified. Rarefaction and Generalized
      Linear Model indicated higher species richness and abundance, respectively, in
      the buffer zone of the dry forest; possible explanations for this finding include
      the intermediate disturbance hypothesis, wherein diversity can be higher in sites
      where disturbance is not very frequent or very intense, and the 'enemies
      hypothesis', wherein structural complexity and high plant diversity favour
      increased predators or, in this case, parasitoids. Diversity was higher during
      the rainy season, which may have been due to the higher availability of
      resources. Vegetation and management had a positive impact on the Coc (attack
      cocoons and pupae) and Myc (attack concealed larvae living in the fruiting bodies
      of mushrooms) parasitoid guilds. Members of the Coc guild are generalist
      parasitoids, which may be favoured in complex vegetation with a high richness of
      potential hosts and non-hosts. The Myc guild requires certain environmental
      conditions that promote fungal growth, such as humidity, that is absent in the
      other vegetation types of savannah and coastal dune scrubland.

PMID- 29166980
TI  - Determination of the efficiency of diets for larval development in mass rearing
      Aedes aegypti (Diptera: Culicidae).
AB  - Larval diet quality and rearing conditions have a direct and irreversible effect
      on adult traits. Therefore, the current study was carried out to optimize the
      larval diet for mass rearing of Aedes aegypti, for Sterile Insect Technique (SIT)
      based applications in Sri Lanka. Five batches of 750 first instar larvae (L1) of
      Ae. aegypti were exposed to five different concentrations (2-10%) of
      International Atomic Energy Agency (IAEA) recommended the larval diet.
      Morphological development parameters of larva, pupa, and adult were detected at
      24 h intervals along with selected growth parameters. Each experiment was
      replicated five times. General Linear Modeling along with Pearson's correlation
      analysis were used for statistical treatments. Significant differences (P < 0.05)
      among the larvae treated with different concentrations were found using General
      Linear Modeling in all the stages namely: total body length and the thoracic
      length of larvae; cephalothoracic length and width of pupae; thoracic length,
      thoracic width, abdominal length and the wing length of adults; along with
      pupation rate and success, sex ratio, adult success, fecundity and hatching rate
      of Ae. aegypti. The best quality adults can be produced at larval diet
      concentration of 10%. However, the 8% larval diet concentration was most suitable
      for adult male survival.

PMID- 29166982
TI  - Abstracts from the New England Society of Allergy Spring Meeting, April 7, 2017,
      Westford, MA.

PMID- 29166981
TI  - Organic vs. organic - soil arthropods as bioindicators of ecological
      sustainability in greenhouse system experiment under Mediterranean conditions.
AB  - Organic greenhouse (OGH) production is characterized by different systems and
      agricultural practices with diverse environmental impact. Soil arthropods are
      widely used as bioindicators of ecological sustainability in open field studies,
      while there is a lack of research on organic production for protected systems.
      This study assessed the soil arthropod abundance and diversity over a 2-year crop
      rotation in three systems of OGH production in the Mediterranean. The systems
      under assessment differed in soil fertility management: SUBST - a simplified
      system of organic production, based on an input substitution approach (use of
      guano and organic liquid fertilizers), AGROCOM - soil fertility mainly based on
      compost application and agroecological services crops (ASC) cultivation (tailored
      use of cover crops) as part of crop rotation, and AGROMAN - animal manure and ASC
      cultivation as part of crop rotation. Monitoring of soil fauna was performed by
      using pitfall traps and seven taxa were considered: Carabidae, Staphylinidae,
      Araneae, Opiliones, Isopoda, Myriapoda, and Collembola. Results demonstrated high
      potential of ASC cultivation as a technique for beneficial soil arthropod
      conservation in OGH conditions. SUBST system was dominated by Collembola in all
      crops, while AGROMAN and AGROCOM had more balanced relative abundance of Isopoda,
      Staphylinidae, and Aranea. Opiliones and Myriapoda were more affected by season,
      while Carabidae were poorly represented in the whole monitoring period. Despite
      the fact that all three production systems are in accordance with the European
      Union regulation on organic farming, findings of this study displayed significant
      differences among them and confirmed the suitability of soil arthropods as
      bioindicators in protected systems of organic farming.

PMID- 29166983
TI  - Comparison Study of Body Image Satisfaction Between Beginning- and Advanced-Level
      Female Ballet Students.
AB  - This mixed methods study compares the level of satisfaction with one's body image
      between beginning- and advanced-level female collegiate ballet students. Thirty
      six beginning-level students were enrolled in two ballet classes, and a second
      group of 16 advanced-level students was enrolled in a third class. A mirror was
      used in the teaching of both groups. During the first and thirteenth week of a 14
      week semester, students completed the Cash 69-item Body Self-Relations
      Questionnaire. In addition, five students from each group were randomly selected
      to participate in semi-structured interviews during the second and last week of
      the semester. Researchers asked students questions about their kinesthetic
      experience and the mirror's role in the studio. The quantitative results
      indicated that over the course of the semester the beginning dancers decreased in
      feeling physically fit, while the advanced dancers felt more in shape. For both
      beginning and advanced dancers there was a decrease in body image satisfaction.
      By semester's end, the advanced dancers were more preoccupied with weight and
      exercised more than the beginning dancers. The interviews revealed that four out
      of the five beginning ballet students discussed the use of the mirror in class
      and reported experiencing thoughts and sensations characteristic of the objective
      self-awareness state, such as heightened self-consciousness, comparison of self
      to others, or negative self-evaluation. The advanced dancers, on the other hand,
      focused on developing ways to avoid the mirror and preferred to "feel" movements
      muscularly before using the mirror for feedback. Even though the advanced dancers
      had more knowledge of how to use a mirror beneficially in class, their body image
      scores were equally as compromised as the beginning students'. These results
      suggest that both beginning- and advanced-level ballet students experience a
      decrease in body image satisfaction in a mirrored studio environment.

PMID- 29166984
TI  - A Comparison of Musculo-Articular Stiffness and Maximal Isometric Plantar Flexion
      and Knee Extension Force in Dancers and Untrained Individuals.
AB  - Dance involves a high volume of aesthetic, stretch-shortening cycle (SSC)
      actions, which may cause unique adaptations to performance. The strength dancers
      possess to withstand such frequency of SSCs remains elusive. The extensive
      training that dancers experience from a young age, however, yields anatomical and
      strength development that may contrast with that of untrained individuals.
      Therefore, the purpose of this study was to investigate differences in musculo
      articular stiffness and maximal isometric plantar flexion and knee extension
      force between dancers and untrained individuals. A total of 16 females
      volunteered to participate in the study (N = 8 dancers; N = 8 untrained
      individuals). Dancers had a minimum of 10 years of dance experience and were
      currently training at the collegiate dance level three or more times per week.
      Untrained individuals had no dance background, nor were they currently involved
      in any form of regularized physical activity. All subjects completed a series of
      lower leg measurements and strength tests. This included a musculo-articular
      stiffness measurement using a free-oscillation technique, along with maximal
      isometric plantar flexion (MIP) and maximal isometric knee extension (MIKE)
      testing. The data indicate that dancers had a significantly greater rate of force
      development and peak force during MIP and rate of force development during MIKE
      in comparison to untrained individuals. Dancers also possessed significantly
      greater musculo-articular stiffness. Hence, the data provide some evidence that
      involvement in dance can result in greater muscle force generating capacity and
      musculo-articular stiffness due to the SSC mechanisms involved in dance
      movements.

PMID- 29166985
TI  - Postural Control During Different Unipodal Positions in Professional Ballet
      Dancers.
AB  - Classical ballet involves the performance of complex movements that require high
      level motor skills and good postural control. This study explored postural sway
      in passe en demi-pointe position in dancers and compared single-leg standing sway
      (with and without visual restriction) between dancers and non-dancers. Fourteen
      professional dancers and 14 sex- and age-matched volunteers who were not ballet
      dancers participated in the study. Participants stood on a force plate on the
      dominant leg in the following positions: 1. single-leg stance with eyes open
      (reference task) and with eyes closed and blindfolded for 35 seconds; and 2.
      passe en demi-pointe position with eyes open for 20 seconds (dancers only). The
      center of pressure signal was used to calculate the following variables: average
      velocity; anteroposterior and mediolateral velocity peaks; anteroposterior and
      mediolateral displacement ranges; average displacement; and ellipse area.
      Significant interaction effects (p < 0.001, eta2 = 0.419) were observed between
      groups and postural tasks, with higher stabilometric values for the dancer group
      during the single-leg stance with eyes closed and blindfolded task, as evidenced
      by the average displacement of 241.0 cm in dancers and 147.1 cm in non-dancers (p
      = 0.025), and by the ellipse area of 9.5 cm2 for dancers and 4.9 cm2 for non
      dancers (p = 0.001). In regard to the positions with eyes open, an increase was
      noted only in the average sway velocity and mediolateral velocity in passe en
      demi-pointe position compared with the single-leg stance with eyes open (p <
      0.001). Greater postural sway might be interpreted as the result of either
      inadequate postural stability or exploratory behavior to maintain postural
      stability in more challenging tasks. It is concluded that professional ballet
      dancers show greater visual dependency for balance adjustment with reduced
      influence of the supporting base on postural sway.

PMID- 29166986
TI  - A Retrospective Assessment of Return to Function in Dance After Physical Therapy
      for Common Dance Injuries.
AB  - An injury that causes a dancer to take time away from training or performance can
      be career ending, and thus it is important for dancers to have accurate
      expectations when considering treatment options. Thus far, few studies have
      reported functional outcomes after injury in dancers, which may be different than
      for the general athletic population. Therefore, our study sought to determine
      functional outcomes in dancers after operative and non-operative treatment for
      common dance injuries. Our outcome measures included a subjective assessment of
      the degree to which a dancer had returned to his or her previous level of dance,
      the SF-12 survey, and the WHO functional outcome scale modified for dance. We
      also compared these as outcome measurement tools for return to full function in
      dance. Secondarily, we sought to assess factors that may have contributed to
      poorer functional outcomes. We reviewed the charts of 675 dancers seen at our
      physical therapy facilities between 2006 and 2010 and identified 416 adult
      dancers who had experienced a dance-related injury that we categorized as
      "common," based on surveys of injuries among dancers (with back injuries
      excluded). One hundred and sixty-four dancers completed a tele- phone survey
      about their recovery after injury. Descriptive statistics, correlation, and
      linear regression were then used to identify factors associated with poor
      functional outcomes. Sixty-three percent of the participants had a full return to
      their pre-injury level. No variables were found to be significantly correlated (p
      < 0.05) with poorer outcomes by linear re- gression. However, there was a trend
      to- ward better outcomes when dancers were younger, their injuries were not
      chronic, and their recovery was not limited by fear. The three measurement tools
      were all highly correlated with one another (p = 0.000) and found to be useful
      determinants of functional return to dance. Given that there were few strongly
      correlated outcome factors, we concluded that poorer functional outcomes in dance
      resulted from a combination of many factors, including those of a psychosocial
      nature. We believe these results can be used to better advise dancers who are
      considering treatment options, provide better estimates of possible limitations
      and time needed to return to dance, and potentially promote easier recoveries and
      better functional outcomes.

PMID- 29166987
TI  - Turnout in Classical Dance: Is It Possible to Enhance the External Rotation of
      the Lower Limb by a Myofascial Manipulation? A Pilot Study.
AB  - Turnout in classical dance refers to the external rotation of the lower
      extremities so that the longitudinal axes of the feet form an angle of up to 180
      degrees . To what extent a myofascial manipulation (myofascial release, MFR)
      could enhance this external rotation is as yet unknown. In this pilot study, 16
      students of dance and 3 dance instructors were randomly assigned to an
      intervention group (IG; N = 10) and a group of controls (CG; N = 9). Isolated
      external hip rotation (EHR) and functional turnout (TO) were evaluated three
      times (pre-, post-, and follow-up measurement) using a plurimeter and Functional
      Footprints(r) rotation discs. In addition, subjectively perceived physical
      flexibility (PPF) was determined by means of a written survey. The interval
      between pre- and post-measurement and between post- and follow-up measurement was
      4 weeks. Only the IG received four 20-minute MFR treatments of the lower limb at
      weekly intervals between pre- and post-measurement. In both the post-measurement
      (pre- versus post-: p = 0.038, d = 0.77) and the follow-up measurement (pre-
      versus follow-up: p < 0.001, d = 1.66) the IG showed a significantly improved
      isolated EHR of the right hip and a significantly increased PPF (pre- versus post
      : p = 0.047, d = 0.73; pre- versus follow-up: p = 0.012, d = 1.00). The left EHR
      as well as the right and left TO were not affected by the intervention. It was
      demonstrated that four sessions of MFR of the lower limb can induce an
      improvement in the isolated external hip rotation (right hip). The beneficial
      effects of the treatment regarding an improvement of functional turnout could not
      be entirely verified in this pilot study. However, the significant increase in
      the participants' subjective flexibility supports the promising trend in the
      objective parameters and emphasizes the need to undertake further research.

PMID- 29166988
TI  - External Focus of Attention Enhances Children's Learning of a Classical Ballet
      Pirouette.
AB  - The purpose of the present study was to investigate the influence of instructions
      promoting an external versus internal focus of attention on the learning of a
      specific balance task, the pirouette en dehors (from fourth position), in 10-year
      old novice ballet students. In addition, we sought to gain insight into learners'
      motivation and subjective learning experience as a function of different focus
      conditions. Thirty-eight children were randomly assigned to one of two groups. In
      the external focus (EF) group, participants were asked to focus on a spotting
      point on the wall in front of them for as long as possible. In the internal focus
      (IF) group, participants were asked to focus on the initial position of their
      head relative to the wall in front of them and on keeping it in that position for
      as long as possible. The task goal was to rotate as far as possible, and the
      dependent variable was the number of degrees rotated. All participants performed
      15 practice trials of a (right) pirouette. Two days later, participants completed
      retention and transfer (left pirouette) tests without attentional focus
      reminders. After the practice phase, participants were asked what they thought
      about while practicing the pirouette and completed self-rating scales related to
      their perceived competence, effort, and sense of the importance of doing well.
      The EF group demonstrated superior performance relative to the IF group during
      practice, retention, and transfer phases. In addition, EF participants' responses
      indicated higher perceived competence and greater satisfaction with their
      performance, as well as greater importance of performing well. In contrast, IF
      participants reported more nervousness and fear of losing balance and not doing
      well. Overall, the findings demonstrate that external relative to internal focus
      instructions enhanced the students' learning of the pirouette en dehors and had
      positive motivational consequences.

PMID- 29166992
TI  - Use of Alum for Odor Reduction in Sludge and Biosolids from Different Wastewater
      Treatment Processes.
AB  - Applicability of alum addition to wastewater sludge and biosolids produced from
      different treatment processes was evaluated as a means of odor reduction. Four
      water resource recovery facilities (WRRFs) were chosen for this study: two used
      mesophilic anaerobic digestion and two used oxidation ditch processes. The
      experiments were conducted on a laboratory scale and in all cases the alum was
      added prior to dewatering. This is the first report of the application of alum
      for odor reduction in oxidation ditch processes. Alum addition was effective in
      reducing odors in anaerobically digested biosolids. Addition of 4% alum to
      anaerobically digested liquid biosolids prior to dewatering resulted in a 60%
      reduction in the peak odor concentration in the laboratory dewatered cake,
      relative to the control sample. Alum addition did not reduce odors in dewatered
      sludge from oxidation ditch processes.

PMID- 29166989
TI  - Use of a Patient-Specific Outcome Measure and a Movement Classification System to
      Guide Nonsurgical Management of a Circus Performer with Low Back Pain: A Case
      Report.
AB  - Low back pain (LBP) can be detrimental to the career of a circus arts performer,
      yet there is minimal population-specific literature to guide care. Moreover,
      reluctance to discontinue training and the need to resume end-range lumbar motion
      can impede the success of conservative care. The purpose of this case report is
      to describe the use of a patient-specific outcome measure and a movement
      classification system to structure a home exercise program (HEP) for an
      adolescent training to be a circus performer. The patient was a 16-year-old
      female with a 10-month history of LBP. A Movement System Impairment examination
      indicated that she had lower abdominal weakness, gluteal weakness, and hip
      flexors that were short and stiff; hence, extension and rotation were repeated
      patterns of lumbopelvic movement associated with her LBP symptoms. The patient
      was seen for 16 visits over 16 weeks. The HEP focused on minimizing lumbopelvic
      extension and rotation movements while improving abdominal and gluteal strength
      and hip flexor flexibility. Resumption of acrobatic activities was guided by the
      Patient-Specific Functional Scale. As measured by this scale, her difficulty with
      five functional and acrobatic activities decreased from 4/10 at initial
      evaluation to less than or equal to 1/10 by discharge. It is concluded that using
      an outcome measure to assess difficulty of activities chosen by the patient and
      education on how to avoid movement patterns associated with LBP symptoms can help
      facilitate return to performance.

PMID- 29166993
TI  - Aerobic Biodegradation of OCDD by P. Mendocina NSYSU: Effectiveness and Gene
      Inducement Studies.
AB  - The goals of this study were to assess the effectiveness of (1) enhancing
      octachlorinated dibenzo-p-dioxin (OCDD) biodegradation under aerobic conditions
      by Pseudomonas mendocina NSYSU (P. Mendocina NSYSU) with the addition of
      lecithin, and (2) inducing OCDD ring-cleavage genes by pentachlorophenol (PCP)
      and OCDD addition. P. Mendocina NSYSU could biodegrade OCDD via aerobic
      cometabolism and lecithin was used as a primary substrate. Approximately 74 and
      67% of OCDD biodegradation was observed after 60 days of incubation with lecithin
      and glucose supplement, respectively. Lecithin was also used as the
      solubilization additive resulting in OCDD solubilization and enhanced
      bioavailability of OCDD to P. Mendocina NSYSU. Two intradiol and extradiol ring
      cleavage dioxygenase genes (Pmen_0474 and Pmen_2526) were identified from gene
      analyses. Gene concentration was significantly enhanced after the inducement by
      PCP and OCDD. Higher gene inducement efficiency was obtained using PCP as the
      inducer, and Pmen_2526 played a more important role in OCDD biodegradation.

PMID- 29166995
TI  - Single-Laboratory Validation of a Method for the Determination of Vitamin D3 in
      Dietary Supplements by Liquid Chromatography with Tandem Mass Spectrometry (LC
      MS/MS).
AB  - A single-laboratory validation (SLV) for the analysis of vitamin D3 was performed
      in four types of dietary supplements (capsules, soft gels, syrups, and tablets)
      using LC-MS/MS. Samples were treated by alkaline saponification for oil-based
      soft gels and utilized EDTA solution for capsules, syrups, and tablets prior to n
      hexane extraction. Vitamin D3 in sample extracts was separated on a reversed
      phase C18 column (100 * 2.1 mm, 2.7 MUm) using a mobile phase of a 95 + 5 (v/v)
      mixture of 5 mM ammonium formate in methanol containing 0.1% formic acid and 5 mM
      ammonium formate in 0.1% formic acid running at a flow rate of 0.2 mL/min.
      Vitamin D3 was confirmed by the presence of three fragment ions at m/z 107, 159,
      and 259 within a defined retention time window from the precursor ion at m/z 385.
      Quantitation was based on the peak area at m/z 367 to that of the internal
      standard (d3-vitamin D3) at m/z 370 with reference to the respective response
      ratios of the calibration standards. The linear response of vitamin D3 ranged
      from 0.10 to 6.29 mg/L and the correlation coefficient (r) of the six-point
      calibration curves was >0.999. Accuracy, in terms of the spiked recoveries from
      blank syrup and starch powder at three different concentration levels, was 101
      103%. Precision, determined by two different analysts over a period of 5 weeks,
      ranged from 2.7 to 7.0% for the four preparations. The SLV demonstrates the
      present LC-MS/MS method is reliable and robust for the determination of vitamin
      D3 in the studied dietary supplements. Considering the attainment of satisfactory
      SLV results, further validation through intra-laboratory collaborative study is
      recommended.

PMID- 29166994
TI  - Biological Phosphorus Recovery: Review of Current Progress and Future Needs.
AB  - This review summarizes the main species of polyphosphate accumulating organisms
      (PAOs) and algae, illustrates their pathways and key enzymes, discusses
      biological phosphorous (P) recovery from dilute waters, and identifies research
      avenues to encourage adoption and implementation. Phylogenic analysis indicates
      that the Proteobacteria phylum plays an important role in enhanced biological
      phosphorus removal (EBPR). The use of meta-transcriptome analysis and single cell
      based techniques to help overcome the challenges associated with non-PAO
      competition was discussed. For algae capable of luxury phosphorus uptake,
      fundamental research is needed to illustrate the phosphorus regulation process
      and key proteins involved. Emerging technologies and processes have great
      potential to further advance phosphorus recovery, including combined PAO/algae
      reactors, bioelectrochemical systems, and biosorption by phosphorus binding
      proteins. As the paradigm shifts toward holistic resource recovery, research is
      needed to explore P+ recovery with other resources (e.g., metals from sludge),
      using a combination of biological and chemical approaches.

PMID- 29166996
TI  - Validation of the MicroSnap Coliform and E. coli Test System for Enumeration and
      Detection of Coliforms and E. coli in a Variety of Foods.
AB  - The MicroSnap Coliform and E. coli system was devised to give rapid enumeration
      and detection of coliforms and/or Escherichia coli strains in a sample of food
      within an 8 h working shift. The method measures beta-galactosidase and beta
      glucuronidase enzymes using novel bioluminogenic substrates which develop an
      output light signal proportional to the concentration of enzyme discovered. The
      assay uses two different phases to determine the enzyme concentration. The first
      phase is an enrichment of the sample in a nutrient-rich broth device at 37 +/-
      0.5 degrees C. After 6 or 8 h, an aliquot is taken from the enrichment device and
      injected into the Coliform Detection Device, which is assayed in a luminometer
      after 10 min of incubation at 37 +/- 0.5 degrees C. Samples testing positive in
      the Coliform Detection Device can be subsequently assayed specifically for E.
      coli using the E. coli Detection Device. The relative light unit output from the
      detection device is proportional to the bacterial concentration when the
      incubation was initiated, which is proportional to the contamination level in the
      matrix being assessed. The MicroSnap Coliform and E. coli system was evaluated
      for both quantitative and qualitative analysis of coliforms and E. coli in a
      variety of foods. Three different luminometers were used in the analysis, each of
      which has different functionalities and different sensitivities. The MicroSnap
      method showed good correlation with the appropriate corresponding reference
      method for enumeration of coliforms and E. coli. A statistically significant
      difference was seen in detection of E. coli in milk, as reported by the
      independent laboratory. The reference method reported higher mean Log10 CFU
      counts than the MicroSnap method; however, no significant differences were seen
      between the MicroSnap system and reference methods for any of the other matrixes.
      Inclusivity testing was conducted on 25 different non-E. coli coliforms and 25
      different E. coli strains, and exclusivity testing was conducted on 30 different
      species of nontarget organisms. Two E. coli strains were not detected in the
      Coliform Detection Device after 8 h on one of the instruments. All other
      inclusivity strains tested were detected after 8 h of incubation. None of the
      exclusivity strains were detected. The lot-to-lot and kit stability studies
      showed no statistical differences between lots or over the term of the shelf
      life. Robustness studies indicate that the timing of incubation for the detection
      phase is critical for correct system functioning.

PMID- 29166997
TI  - MicroSEQ(r) Salmonella spp. Detection Kit Using the Pathatrix(r) 10-Pooling
      Salmonella spp. Kit Linked Protocol Method Modification.
AB  - : Real-time PCR methods for detecting foodborne pathogens offer the advantages of
      simplicity and quick time to results compared to traditional culture methods. The
      addition of a recirculating pooled immunomagnetic separation method prior to real
      time PCR analysis increases processing output while reducing both cost and labor.
      This AOAC Research Institute method modification study validates the MicroSEQ(r)
      Salmonella spp. Detection Kit [AOAC Performance Tested Method (PTM) 031001]
      linked with the Pathatrix(r) 10-Pooling Salmonella spp. Kit (AOAC PTM 090203C) in
      diced tomatoes, chocolate, and deli ham. The Pathatrix 10-Pooling protocol
      represents a method modification of the enrichment portion of the MicroSEQ
      Salmonella spp. PROTOCOL: The results of the method modification were compared to
      standard cultural reference methods for diced tomatoes, chocolate, and deli ham.
      All three matrixes were analyzed in a paired study design. An additional set of
      chocolate test portions was analyzed using an alternative enrichment medium in an
      unpaired study design. For all matrixes tested, there were no statistically
      significant differences in the number of positive test portions detected by the
      modified candidate method compared to the appropriate reference method. The
      MicroSEQ Salmonella spp. protocol linked with the Pathatrix individual or 10
      Pooling procedure demonstrated reliability as a rapid, simplified, method for the
      preparation of samples and subsequent detection of Salmonella in diced tomatoes,
      chocolate, and deli ham.

PMID- 29166998
TI  - Evaluation of the Thermo ScientificTM SureTectTM Listeria species Assay.
AB  - The Thermo ScientificTM SureTectTM Listeria species Assay is a new real-time PCR
      assay for the detection of all species of Listeria in food and environmental
      samples. This validation study was conducted using the AOAC Research Institute
      (RI) Performance Tested MethodsSM program to validate the SureTect Listeria
      species Assay in comparison to the reference method detailed in International
      Organization for Standardization 11290-1:1996 including amendment 1:2004 in a
      variety of foods plus plastic and stainless steel. The food matrixes validated
      were smoked salmon, processed cheese, fresh bagged spinach, cantaloupe, cooked
      prawns, cooked sliced turkey meat, cooked sliced ham, salami, pork frankfurters,
      and raw ground beef. All matrixes were tested by Thermo Fisher Scientific,
      Microbiology Division, Basingstoke, UK. In addition, three matrixes (pork
      frankfurters, fresh bagged spinach, and stainless steel surface samples) were
      analyzed independently as part of the AOAC-RI-controlled independent laboratory
      study by the University of Guelph, Canada. Using probability of detection
      statistical analysis, a significant difference in favour of the SureTect assay
      was demonstrated between the SureTect and reference method for high level spiked
      samples of pork frankfurters, smoked salmon, cooked prawns, stainless steel, and
      low-spiked samples of salami. For all other matrixes, no significant difference
      was seen between the two methods during the study. Inclusivity testing was
      conducted with 68 different isolates of Listeria species, all of which were
      detected by the SureTect Listeria species Assay. None of the 33 exclusivity
      isolates were detected by the SureTect Listeria species Assay. Ruggedness testing
      was conducted to evaluate the performance of the assay with specific method
      deviations outside of the recommended parameters open to variation, which
      demonstrated that the assay gave reliable performance. Accelerated stability
      testing was additionally conducted, validating the assay shelf life.

PMID- 29166999
TI  - Evaluation of the Thermo ScientificTM SureTectTM Salmonella species Assay.
AB  - The Thermo ScientificTM SureTectTM Salmonella species Assay is a new real-time
      PCR assay for the detection of Salmonellae in food and environmental samples.
      This validation study was conducted using the AOAC Research Institute (RI)
      Performance Tested MethodsSM program to validate the SureTect Salmonella species
      Assay in comparison to the reference method detailed in International
      Organization for Standardization 6579:2002 in a variety of food matrixes, namely,
      raw ground beef, raw chicken breast, raw ground pork, fresh bagged lettuce, pork
      frankfurters, nonfat dried milk powder, cooked peeled shrimp, pasteurized liquid
      whole egg, ready-to-eat meal containing beef, and stainless steel surface
      samples. With the exception of liquid whole egg and fresh bagged lettuce, which
      were tested in-house, all matrixes were tested by Marshfield Food Safety,
      Marshfield, WI, on behalf of Thermo Fisher Scientific. In addition, three
      matrixes (pork frankfurters, lettuce, and stainless steel surface samples) were
      analyzed independently as part of the AOAC-RI-controlled laboratory study by the
      University of Guelph, Canada. No significant difference by probability of
      detection or McNemars Chi-squared statistical analysis was found between the
      candidate or reference methods for any of the food matrixes or environmental
      surface samples tested during the validation study. Inclusivity and exclusivity
      testing was conducted with 117 and 36 isolates, respectively, which demonstrated
      that the SureTect Salmonella species Assay was able to detect all the major
      groups of Salmonella enterica subspecies enterica (e.g., Typhimurium) and the
      less common subspecies of S. enterica (e.g., arizoniae) and the rarely
      encountered S. bongori. None of the exclusivity isolates analyzed were detected
      by the SureTect Salmonella species Assay. Ruggedness testing was conducted to
      evaluate the performance of the assay with specific method deviations outside of
      the recommended parameters open to variation (enrichment time and temperature,
      and lysis temperature), which demonstrated that the assay gave reliable
      performance. Accelerated stability testing was additionally conducted, validating
      the assay shelf life.

PMID- 29167000
TI  - [Study on Genetype in Lung Squamous Carcinoma by High-throughput of
      ?Transcriptome Sequence].
AB  - BACKGROUND: Recently, there is no effective targeted drug for to the lung
      squamous carcinoma, the targeted drug for the adenocarcinoma does not benefit for
      the patients with squamous lung cancer, and researchers have known less targets
      for this type of patients. The main study herein is to screen and identify the
      specific key genes for the lung squamous carcinoma that will provide potential
      novel targets to describe pathogenesis of lung cancer. METHODS: Transcript
      sequence was used to detect the five pairs lung squamous carcinoma and normal
      lung tissues and bioinformatics was performed to investigate the differential
      coding genes between them and quantitative PCR was done to validate the key genes
      expression in lung cancer cell lines. RESULTS: The results of transcriptome
      sequence showed that 534 genes were up-regulated in the tumor tissues compared
      with the corresponding normal tissues. The top ten increased genes in the tumors
      were GAGE12J, SPRR3, PRAME, SPRR1A, SPRR2E, MAGEA3, SPRR1B, IL36G and TMPRSS11D.
      Next, we identified expression of SPRR family in lung cancer cell lines H520,
      GLC82, A549, H1299 and PC9. And we found higher expression of SPRR family genes
      in H1299 cells which metastasized to the lymph node. CONCLUSIONS: SPRR family
      genes are identified to be highly expressed in the lung squamous carcinoma by
      high throughput transcript sequencing. This SPRR family genes are associated with
      lymph node metastasis that provide novel idea for lung cancer therapy.?.

PMID- 29167001
TI  - [Association between the ALK Gene Status and the Efficacy of First-line
      ?Pemetrexed Chemotherapy in Patients with Advanced Lung Adenocarcinoma].
AB  - BACKGROUND: Anaplastic lymphoma kinase (ALK) is one of the major driver genes of
      non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy
      of pemetrexed in ALK-positive lung cancer is controversial. The aim of this study
      is to explore the efficacy of pemetrexed-based chemotherapy in patients with ALK
      positive and negative lung adenocarcinoma. METHODS: The clinical data of 98 cases
      of epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene
      (KRAS), V-rafmurine sarcoma viral oncogene homolog B1 (BRAF)-negative patients
      with advanced lung adenocarcinoma patients who diagnosed by histopathology from
      January 2015 to April 2016 in the First Affiliated Hospital of Zhengzhou
      University were collected. The relationships between ALK gene status, clinical
      characteristics and response and progression-free survival (PFS) were analyzed.
      RESULTS: All of the 98 patients' ALK status were determined. ALK gene fracture
      fusion occured in 34 cases (34.7%), no fracture fusion in 64 cases (65.3%). All
      patients underwent first-line pemetrexed and platinum-based chemotherapy, the
      objective response rate (ORR) was 21.4% and the disease control rate (DCR) was
      84.7%. The ORR and DCR of patients with ALK fracture fusion were higher than
      those without fracture fusion (41.2% vs 10.9%, chi2=23.389, P<0.001; 91.2% vs
      81.3%, chi2=4.153, P=0.042), the difference was statistically significant. ALK
      gene status was not related to age, gender, smoking history and clinical stage.
      The median PFS of ALK-positive lung adenocarcinoma was 7.1 months (95%CI: 6.1
      8.1) and negative was 4.7 months (95%CI: 3.818-5.582), and the difference was
      statistically significant (chi2=13.269, P<0.001). Cox multivariate analysis
      indicates that PFS of pemetrexed combined with platinum chemotherapy was
      independent of gender, age, smoking, staging and platinum. ALK gene fracture
      fusion is an independent factor affecting PFS (HR=0.392, 95%CI: 0.243-0.634,
      P<0.001). CONCLUSIONS: ALK-positive lung adenocarcinoma patients with first-line
      pemetrexed-based chemotherapy have greater clinical benefit than ALK-negative
      patients.

PMID- 29167002
TI  - [Efficacy and Toxicity of Metronomic Oral Vinorelbinen in Advanced Non-small Cell
      Lung Cancer after Failure to Multiple-lines Treatments].
AB  - BACKGROUND: The development of new treatments beyond first-line in metastatic non
      small cell lung cancer (NSCLC) contributed to the increase in overall survival.
      Metronomic chemotherapy involves several mechanisms of anti-tumor with less
      toxicity. Oral vinorelbine has paved the way for innovative treatment strategies
      through metronomic regimens. Therefore, this study assessed the efficacy and
      safety of metronomic oral vinorelbinen in advanced NSCLC after failure to
      multiple-lines treatments. METHODS: Our retrospective study enrolled 26 patients
      who received metronomic oral vinorelbinen. Survival factors were evaluated by
      univariate regression analysis. RESULTS: The median follow-up time was 4 months
      (range 2-12). The median number of treatment cycles was 2 (range 1-8). No patient
      achieved complete remission, 2 cases (8%) partial remission, 11 cases (42%)
      stable disease, 13 cases (50%) progression disease. Overall response rate was 8%
      and disease control rate was 50%. The median progression-free survival (PFS) was
      2 months. In univariate analysis, patients with performance status (PS)=1 had a
      statistically significantly longer PFS than patients with PS=2. Gender, age,
      smoking status and histology were not prognostic factors according to PFS.
      Treatment was well tolerated with rare serious toxicity. No grade 4 adverse
      events (AEs) or occurrences of intolerable toxicity were observed. There was no
      treatment-related death and none of the study patients required hospitalization
      for treatment-related adverse events. CONCLUSIONS: Metronomic oral vinorelbinen
      is effective in advanced NSCLC after the failure of multiple lines treatments
      with an acceptable AE profile, especially in patients with high PS.?.

PMID- 29167003
TI  - [Prognostic Analysis of Patients with Advanced Non-small Cell Lung Cancer ?in
      Different Genotypes].
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) has been transformed from the
      treatment according to histological type to genotype treatment model. The
      epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)
      genes are the most important drivers in lung cancer. The aim of this study is to
      explore the clinical characteristics and prognostic factors of patients with
      advanced NSCLC with different genotypes. METHODS: We retrospectively reviewed the
      clinical data of 553 advanced NSCLC patients with EGFR mutations and ALK positive
      who were hospitalized in the Beijing Chest Hospital from July 2004 to December
      2015, and the independent prognostic factors of patients were analyzed by Cox
      proportional hazards regression model. RESULTS: The clinical data of 553 patients
      (227 with EGFR mutations, 58 with ALK positive, 2 with EGFR and ALK co-mutation
      and 266 with wild-type) with advanced NSCLC were enrolled in this study. The
      median survival time of 227 patients with EGFR mutations was 28.7 mo (95%CI:
      22.160-35.240), and the performance status (PS) score (0-1) (HR=4.451; 95%CI:
      2.112-9.382; P<0.001) and EGFR-tyrosine kinase inhibitors (TKIs) targeted therapy
      (HR=2.785; 95%CI: 1.871-4.145; P<0.001) were the independent prognostic factors
      for the survival of patients harboring EGFR mutations. The median survival time
      of 58 patients with ALK positive was 15.5 mo (95%CI: 10.991-20.009), and
      treatment with crizotinib (P=0.022) was the independent influence factor for the
      survival of ALK positive patients. The median survival time of 266 patients with
      wild-type was 12.1 mo (95%CI: 10.660-13.540), and the PS score (0-1) (HR=2.313;
      95%CI: 1.380-3.877; P=0.001) and treatment with chemotherapy (HR=1.911; 95%CI:
      1.396-2.616; P<0.001) were the independent prognostic factors for the survival of
      wild-type patients CONCLUSIONS: The prognosis of patients with advanced NSCLC is
      associated with genetic mutation, and targeted therapy has a improvement on
      survival for patients with EGFR mutations or ALK rearrangement.

PMID- 29167004
TI  - [A Programmed Procedure of Prosthetic Reconstruction of the Superior Vena Cava
      ?for Thoracic Tumors via Median Thoracotomy].
AB  - BACKGROUND: The involvement of superior vena cava is a common condition in
      locally advanced thoracic tumors. Patients may benefit from the high risk
      operation. This study proposed a programmed procedure to optimize surgical
      techniques, which can facilitate the safety of operation via median thoracotomy.
      METHODS: A total of 35 patients with thoracic disease involved superior vena cava
      underwent prosthetic vascular reconstruction via median thoracotomy. All patients
      were confirmed locally advanced without distant metastasis including 16 pulmonary
      neoplasm and 19 mediastinal disease. The operations proceed from left to right
      with one direction manner. The initial part of the left innominate vein was
      dissected, then cut off, so as to lift tumor, the pericardium was opened, and the
      left innominate vein and the right artrium were bridged with prosthetic vascular.
      The proximal end of the superior vena cava which not invaded was dissected and
      the tumor was pulled to the caudal side, the right mediastinal pleura was opened
      and the right inner mammary vascular was ligated and the right innominate vein
      was fully revealed. Stretch the tumor to left top, cut azygos vein on above the
      hilum, then block the right innominate vein and superior vena cava, removed
      involved part of blood vessels, the right innominate vein and superior vena cava
      was connected with prosthetic vascular. With these procedures the superior vena
      cava was reconstructed completely. RESULTS: The operation was completed
      successfully in all cases. Postoperative complications included 6 cases with
      arrhythmia, 5 cases with hypoxemia, 1 case with myasthenia crisis, 1 case with
      cardiac hernia, and 2 cases with fungal infection. 2 patients died of myocardial
      infarction and lung infection respectively with a mortality rate of 5.12%. The
      remaining 33 cases were discharged successfully. The average postoperative
      hospital stay was 15 days. Of the 10 patients with superior vena cava syndrome
      preoperatively, 8 patients had symptoms relief except 2 cases with intraoperative
      intravascular thrombosis. CONCLUSIONS: We recommended the programmed procedure of
      prosthetic reconstruction of the superior vena cava, standardize the details of
      treatment, and minimize the risk during operation. The safe surgical procedures
      of this group of cases confirm this practice.

PMID- 29167005
TI  - [Distribution and Clinical Significance of CTLA-4, PD-1 and PD-L1 in Peripheral
      Blood of Patients with Small Cell Lung Cancer].
AB  - BACKGROUND: The aim of this study is to explore cytotoxic T lymphocyte associated
      antigen 4 (CTLA-4), programmed death 1 (PD-1) and programmed death ligand 1 (PD
      L1) distribution and clinical value in liquid biopsy (such as blood) of small
      cell lung cancer (SCLC) patients. METHODS: A total of 60 healthy and 290
      chemotherapy-naive patients with SCLC were recruited. Venous blood samples were
      collected prior to chemotherapy (baseline) and after the second cycle of
      chemotherapy (2nd cycle), and flow cytometry was used to analyze the level of
      CTLA-4, PD-1 or PD-L1 with or without CD3, CD4, CD8 or CD25. Immunocytochemical
      method was used to detect PD-L1 expression in SCLC cell line H446. RESULTS: Cells
      of CTLA-4+ and PD-1+ in SCLC peripheral blood were (1.56+/-1.24)% and (8.07+/
      3.97)%; there is no significant difference between CD3+CTLA-4+ and CD4+CTLA-4+,
      (4.87+/-5.18)% and (3.85+/-2.60)%, but show lower expression than CD3+PD-1+ and
      CD4+PD-1+ (26.63+/-9.04)% and (20.79+/-9.41)%, respectively. However, the level
      of CD4+CD25+CTLA-4+ cells were remarkably higher in SCLC than that in control,
      (7.09+/-5.09)% vs (1.91+/-1.27)%, P<0.001 and CD8+PD-1+ cells were less in SCLC
      than that in control, (11.47+/-5.85)% vs (22.56+/-4.21)%, P<0.001, both of which
      were not associated with age, sex, smoke or disease stage. Level of CD4+CD25+CTLA
      4+ cells and CD8+PD-1+ cells was dropped (5.11+/-2.60)% vs (6.94+/-4.91)% and
      (8.74+/-3.39)% vs (11.48+/-5.91)% after 2nd cycle compare to that at baseline
      (P<0.000,1). Neither the level of CD4+CD25+CTLA-4+ nor CD8+PD-1+ cells before or
      after treatment was related to progression-free disease or overall survival of
      patients. Although PD-L1 was highly expressed in H446 cell cytoplasm and
      membrane, it was rarely found in peripheral blood. CONCLUSIONS: The data we
      presented here showed that CTLA-4 was highly expressed in regulatory T cells and
      PD-1 decreased in CD8+ T cells in peripheral blood of SCLC patients, suggesting
      their unique mechanisms involved in immune regulation. CD4+CD25+CTLA-4+ level
      changed after treatment implies its potential role in predicting treatment
      efficacy.?.

PMID- 29167006
TI  - [Efficacy and Survival Analysis of Apatinib in Patients with Advanced Nonsquamous
      Non-small Cell Lung Cancer after Failure of First-line Treatment].
AB  - BACKGROUND: The efficacy of second or third-line chemotherapy in advanced non
      small cell lung cancer (NSCLC) patients is low. The use of targeted drugs brings
      survival benefit for some patients. Apatinib, as a novel small molecule
      antiangiogenic drug, has demonstrated satisfactory anticancer activity across a
      broad range of malignancies. The aim of this study is to evaluate the efficacy
      and safety of apatinib in patients with advanced NSCLC after first-line treatment
      failure. METHODS: A retrospective study of 128 patients was conducted to evaluate
      the safety, short-term efficacy and survival status with different regimens.
      Kaplan-Meier method and Cox regression model were used for analysis. RESULTS:
      Compared with chemotherapy alone, the median progression free survival (PFS) in
      apatinib monotherapy, chemotherapy alone and apatinib combined with chemotherapy
      were 3.0 (P=0.381), 3.7 and 6.0 months (P<0.001), respectively. The median
      overall survival (OS) were 6.0 (P=0.494), 6.5 and 9.0 months (P=0.001),
      respectively. The incidence of adverse events in grades 3-4 were 18.5%, 15.8% and
      16.0%, respectively (P=0.947). Different treatment regimens (P=0.018) and
      performance status (PS)(P<0.001) were the independent factors of PFS. The smoking
      history (P=0.014), treatment regimens (P=0.002) and PS (P<0.001) were independent
      influencing factors of OS. CONCLUSIONS: Apatinib has a good security. After first
      line treatment failure of lung cancer, chemotherapy combined with apatinib in
      second or third-line is beneficial in PFS and OS when compared with chemotherapy
      alone. But when making comparison between apatinib monotherapy and chemotherapy
      alone, there is no significant difference in PFS and OS. Patients who never smoke
      or has a better PS or use combination therapy have longer survival time.?.

PMID- 29167007
TI  - [MicroRNA-26a and Tumor].
AB  - MicroRNAs are a class of small noncoding RNAs (20-22 nucleotides). MicroRNAs
      regulate gene expression by directly binding gene's 3'-UTR regions. Many studies
      reveal that miRNAs play roles in tumorigenesis. MiR-26a plays different roles in
      different types of cancer, and participates in tumor growth, invasion,
      metastasis, angiogenesis, metabolism, diagnosis and prognosis. This review
      summarizes the progress of miR-26a study in cancer.

PMID- 29167008
TI  - [New Progress in the Relationship between Immune Cells, PD-1 ?in Tumor
      Microenvironment and the Efficacy of EGFR-TKIs].
AB  - In recent years, targeted therapy of epidermal growth factor receptor-tyrosine
      kinase inhibitor (EGFR-TKIs) is the leading treatment modality for patients with
      advanced non-small cell lung cancer (NSCLC) and EGFR gene mutation. However, with
      the prolongation of the medication time, most of the patients appeared drug
      resistance. Tumor microenvironment is the internal environment for the survival
      and development of tumor cells. The immune response which mediated by immune
      cells, like regulatory T (Treg), dendritic cells, macrophages, fibroblasts, etc.
      And the programmed cell death receptor 1 (PD-1) with its ligand PD-1L/PD-2L may
      participate in the drug resistance of EGFR-TKIs. This review will elaborate the
      possible mechanism of the interaction of immune cells on EGFR-TKIs in the tumor
      microenvironment, in order to seek new targets, and further improve the anti
      tumor efficacy and prolong the effective time of EGFR-TKIs.

PMID- 29167010
TI  - [Solitary AAH Arising from Extralobar Sequestration in A Less Than 3-year-old
      Boy: A Case Report].
AB  - We present a case of two-year old boy with solitary atypical adenomatous
      hyperplasia (AAH) in extralobar sequestration (ELS), which was misdiagnosed as
      diaphragmatic hernia before surgery. Review of AAH and pulmonary sequestration
      (PS) revealed that the present case is the youngest of solitary AAH and also the
      first report of solitary AAH arising in ELS without a primary lung cancer. In a
      sense, the present case firstly supports the hypothesis that ELS may be an
      underlying cancer predisposition syndrome, so aggressive surgical therapy should
      be recommended for ELS.

PMID- 29167009
TI  - [Advances of the Role of Lung Cancer Driver Gene and PD-1/PD-L1 Pathway
      Interaction in the Tumorigenesis and Progression of Non-small Cell Lung Cancer].
AB  - Programmed death 1 (PD-1) and programmed death 1 ligand (PD-L1) pathway is a key
      mechanism of immune regulation, and its abnormal activation in tumor tissues
      suggests that PD-1/PD-L1 pathway may participate in the regulation of tumor
      immune escape. Driver gene mutation which is known as a key factor in the
      tumorigenesis of non-small cell lung cancer (NSCLC), was also reported to play a
      important role in the process of tumor immune escape. It indicates that there is
      an interaction between driver gene and PD-1/PD-L1 pathway. The purpose of this
      paper is to review the relationship between PD-1/PD-L1 pathway and lung cancer
      driver gene, such as epidermal growth factor receptor (EGFR), Kirsten rate
      sarcoma viral oncogene homolog (KRAS) and echinoderm microtubuleassociated
      protein-like 4 - anaplastic lymphoma kinase (EML4-ALK) and to summarize the role
      of lung cancer driver gene and PD-1/PD-L1 pathway interaction in the
      tumorigenesis and progression of NSCLC.

PMID- 29167012
TI  - [Report of the First Investigator Conference on the Register Study ?of Advanced
      Non-small Cell Lung Cancer Patients in 2017].

PMID- 29167011
TI  - [Four Cases Report on Primary Lung Adenoid Cystic Carcinoma].
AB  - BACKGROUND: Lung adenoid cystic carcinoma is a kind of rare lung cancer.
      Diagnosis and treatment is not enough understandable for them. We collected and
      analyzed 4 cases of lung adenoid cystic carcinoma for broadening the sight of
      this disease. METHODS: Retrospectively analysed the 4 cases we collected from
      Hunan Cancer Hospital Between January 2012 and December 2016. We depicted the
      pathology, immunohistochemical, epidermal growth factor receptor (EGFR) mutation
      and anaplastic lymphoma kinase (ALK) arrangement in these cases. And the methods
      of the diagnosis and treatment were analyzed. RESULTS: Lung adenoid cystic
      carcinoma is usually located in the airway, EGFR mutation and ALK arrangement is
      rare in this disease. Generally the metastasis of the lung cancer occurred in the
      advanced stage. The prognosis is good if the mass could be resected completely.
      CONCLUSIONS: Diagnosis of the lung adenoid cystic carcinoma depends on
      pathological experiments, surgery is the main treatment in the early stage,
      radiotherapy and chemotherapy is an advisable therapy in the advanced stage. And
      the prognosis of this kind of lung cancer is better than small cell lung cancer
      and non-small cell lung cancer.

PMID- 29167013
TI  - Bovine oviductal and uterine fluid support in vitro embryo development.
AB  - In order to mimic the maternal oviductal environment, we evaluated the effect of
      oviductal fluid (OF) and/or uterine fluid (UF) supplementation on in vitro embryo
      development and quality. In vitro-produced zygotes were cultured with 1.25% OF
      from Day 1 to Day 4 after insemination (OF group), 1.25% OF from Day 1 to Day 4
      followed by 1.25% UF from Day 4 to Day 9 (OF+UF group) or 1.25% UF only from Day
      4 to Day 9 (UF group). Control groups were cultured in the presence of synthetic
      oviduct fluid (SOF) supplemented with 3mgmL-1 bovine serum albumin (BSA) or 5%
      fetal calf serum (FCS). Supplementation of the culture medium with OF and/or UF
      (both at 1.25%) supported embryo development (Day 9 blastocyst rate 28.2-30.6%).
      At 72h after vitrification-warming, the survival of blastocysts from the OF and
      OF+UF groups was similar to that of blastocysts in the SOF+BSA group (61.0+/-5.7%
      and 62.8+/-6.4% vs 64.8+/-6.4% respectively), but significantly higher than that
      of blastocysts from the SOF+FCS group (31.6+/-4.9%; P<0.001). Blastocysts from
      the OF group exhibited upregulation of epigenetic genes (i.e. DNA
      methyltransferase 3alpha (DNMT3A) and insulin-like growth factor 2 receptor
      (IGF2R)), compared with expression in the SOF+FCS group (P<0.05). Whereas those
      from OF+UF and UF groups exhibited downregulation of oxidative stress genes
      compared to SOF+BSA and OF groups for glutathione peroxidase (GPX1) and to
      SOF+FCS, SOF+BSA and OF groups for chloride intracellular channel 1 (CLIC1)
      (P<0.05). In addition, accumulation of reactive oxygen species was lower in
      blastocysts from the OF, OF+UF and UF groups. In conclusion, the use of low
      concentrations of OF and UF in in vitro serum-free culture supports embryo
      development, with OF providing a better control of embryo methylation, whereas UF
      may have antioxidant activity.

PMID- 29167014
TI  - The effect of age and body composition on body mass estimation of males using the
      stature/bi-iliac method.
AB  - The stature/bi-iliac breadth method provides reasonably precise, skeletal frame
      size (SFS) based body mass (BM) estimations across adults as a whole. In this
      study, we examine the potential effects of age changes in anthropometric
      dimensions on the estimation accuracy of SFS-based body mass estimation. We use
      anthropometric data from the literature and our own skeletal data from two
      osteological collections to study effects of age on stature, bi-iliac breadth,
      body mass, and body composition, as they are major components behind body size
      and body size estimations. We focus on males, as relevant longitudinal data are
      based on male study samples. As a general rule, lean body mass (LBM) increases
      through adolescence and early adulthood until people are aged in their 30s or
      40s, and starts to decline in the late 40s or early 50s. Fat mass (FM) tends to
      increase until the mid-50s and declines thereafter, but in more mobile
      traditional societies it may decline throughout adult life. Because BM is the sum
      of LBM and FM, it exhibits a curvilinear age-related pattern in all societies.
      Skeletal frame size is based on stature and bi-iliac breadth, and both of those
      dimensions are affected by age. Skeletal frame size based body mass estimation
      tends to increase throughout adult life in both skeletal and anthropometric
      samples because an age-related increase in bi-iliac breadth more than compensates
      for an age-related stature decline commencing in the 30s or 40s. Combined with
      the above-mentioned curvilinear BM change, this results in curvilinear estimation
      bias. However, for simulations involving low to moderate percent body fat, the
      stature/bi-iliac method works well in predicting body mass in younger and middle
      aged adults. Such conditions are likely to have applied to most human
      paleontological and archaeological samples.

PMID- 29167015
TI  - Quantification of fat infiltration in the sacroiliac joints with ankylosing
      spondylitis using IDEAL sequence.
AB  - AIM: To quantitatively assess fat infiltration in the sacroiliac joints (SIJs) of
      patients with ankylosing spondylitis (AS) by measuring the fat/water signal
      ratios of periarticular bone marrow with iterative decomposition of water and fat
      with echo asymmetry and least square estimation (IDEAL). MATERIALS AND METHODS:
      Routine SIJ magnetic resonance imaging (MRI) and IDEAL were performed on 40
      patients with AS and 30 healthy subjects. The fat infiltration regions (FIRs) and
      normal-appearing regions (NARs) of patients were measured based on the fat/water
      signal intensity on IDEAL. RESULTS: AS patients had higher fat/water signal
      ratios on FIRs and NARs (65.4-85.4%, p<0.05, and 44.1-70.7%, p<0.05,
      respectively) compared to healthy controls (38.3-43.3%). After treatment, the
      fat/water signal ratios of FIRs and NARs decreased (42.1-53.7% and 41.5-50.3%,
      respectively), but they remained higher than in the healthy controls (p<0.05).
      The fat infiltration was detected more effectively with a fat fraction map of the
      IDEAL sequence (95%) than other sequences, including the T1-weighted sequence
      (65%), and the fat/water signal ratios of the sacrum and ilium between the left
      and right sides of SIJs were approximately the same. CONCLUSION: The findings of
      this study suggest that IDEAL may be useful as a quantitative and objective
      method for evaluating the fat infiltration in the periarticular bone marrow of
      SIJs with AS; additionally, the sensitivity of IDEAL is better than that of
      routine sequences in detecting micro-fat infiltration of SIJs, and IDEAL can be
      used to quantitatively measure the adipose content and monitor patient follow-up
      after AS treatment.

PMID- 29167016
TI  - Editorial Comment.

PMID- 29167017
TI  - Author Reply.

PMID- 29167018
TI  - Impact of statin use on the prognosis of patients with hepatocellular carcinoma
      undergoing liver resection: a subgroup analysis of patients without chronic
      hepatitis viral infection.
AB  - BACKGROUND: Statins have been reported to reduce the risk of hepatocellular
      carcinoma (HCC). The effect of perioperative statin use on the prognosis of HCC
      patients undergoing liver resection remains unclear. METHODS: We retrospectively
      analyzed 643 patients who underwent curative liver resection for HCC. Patients
      negative for hepatitis B surface antigen and hepatitis C antibody were classified
      as the non-B non-C HCC subgroup (n = 204). Perioperative statin users were
      defined as patients preoperatively receiving statin medications and maintaining >
      28 cumulative defined daily doses after liver resection. The recurrence-free
      survival (RFS) and overall survival (OS) according to statin use were analyzed in
      the overall HCC cohort or in the non-B non-C HCC subgroup. RESULTS: Among a total
      of 643 (HCC) patients, 43 patients (6.7%) received perioperative statin
      medications. In statin users, the proportion of non-B non-C HCC patients was
      significantly higher than in nonstatin users. Statin users had a high prevalence
      of obesity and diabetes, as well as dyslipidemia. The liver function of statin
      users was better than that of nonstatin users. The multivariate survival analysis
      revealed that use of statins was significantly associated with improvement of RFS
      (hazard ratio [HR], .42; 95% confidence interval [CI], 0.25-0.71; P = .001), but
      not with OS (HR, 0.62; 95% CI, 0.30-1.27; P = .19). In the subgroup analysis of
      the non-B non-C HCC cohort, statin use was significantly associated with
      improvement of RFS (HR, 0.47; 95% CI, 0.22-0.99; P = .04). CONCLUSION:
      Perioperative statin use was associated with an improvement of RFS in HCC
      patients undergoing curative liver resection.

PMID- 29167019
TI  - Reassessing the utility of CT angiograms in penetrating injuries to the
      extremities.
AB  - BACKGROUND: Computed tomography angiography has become routine in the management
      of penetrating trauma to the extremity. Our objective was to evaluate the
      efficacy of physical examination findings compared with computed tomography
      angiography for detection of clinically significant vascular injuries associated
      with penetrating trauma to the extremity. METHODS: This was a retrospective chart
      review of patients presenting to a single level 1 trauma center from January 2013
      June 2016. Patients with penetrating trauma to the extremity and no hard signs of
      vascular injury were included. Physical examination and computed tomography
      angiography findings were analyzed, with particular focus given to missed
      injuries. RESULTS: We identified 393 patients with penetrating trauma to the
      extremity without hard signs of vascular injury. Computed tomography angiography
      was performed in 114 patients (29%). Four patients with distal pulses documented
      on their initial trauma surveys were found to have vascular injuries on computed
      tomography angiography, although 3 of these injuries were identified on repeat
      physical examination. One additional patient had a delayed presentation of a
      pseudoaneurysm. No mortality or limb loss resulted from these injuries. Total
      hospital charges for computed tomography angiography amounted to over $700,000.
      CONCLUSION: Patients with penetrating trauma to the extremity and no hard signs
      of vascular injury do not require computed tomography angiography for
      identification of clinically relevant vascular injuries that require emergent
      operative repair. Serial physical examination appears to provide accurate
      detection of vascular injury requiring procedural intervention.

PMID- 29167020
TI  - Laboratory validation of a point velocity probe for measuring horizontal flow
      from any direction.
AB  - The point-velocity probe (PVP) quantifies groundwater speed and flow direction,
      i.e., velocity, at the centimeter scale. The first probe designs required that
      the flow direction be known a priori, within about 100 degrees  in order to
      position the probe during installation. This study introduces and assesses a '360
      degrees  PVP' that measures flow from any direction without foreknowledge of the
      groundwater velocity. In tests conducted in a Nested Storage Tank (NeST) aquifer
      simulator packed with sand, PVP-measured velocities matched expected velocities
      within +/-9 degrees  in direction and +/-15% in magnitude, on average, consistent
      with previously reported PVP performances in laboratory studies. In tests
      involving 17 repacked NeSTs, the measured and expected velocities were within +/
      30 degrees  and +/-30% on average, illustrating the sensitivity of flow to porous
      medium packing, and the probes' ability to sense these changes; the porosity was
      found to vary considerably between packings i.e., n=0.34+/-0.2. For flow
      directions between 0 degrees  and 80 degrees  of an injection port, the
      experimental error on velocity magnitude was within the ranges reported above. At
      higher flow angles, experimental sources of error contributed to greater
      uncertainties. Fortunately, in these cases there were always alternative
      injection ports (with lower angles to flow) that could be used to circumvent any
      biases. At low experimental flow angles (<10 degrees ) the calculated values
      tended to overestimate the actual flow angles. Fortunately, these cases were
      identifiable by the detection of tracer at detectors on either side of the active
      injection port. In several tests designed with an expected flow direction of 0
      degrees , averaging the calculated directions from each side of the injection
      port resulted in improved matches to the expected flow direction.

PMID- 29167021
TI  - Diffuse large B-cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin
      lymphoma worldwide, representing approximately 30-40% of all cases in different
      geographic regions. Patients most often present with a rapidly growing tumour
      mass in single or multiple, nodal or extranodal sites. The most common type of
      DLBCL, designated as not otherwise specified, represents 80-85% of all cases and
      is the focus of this review. There are also rare types of lymphoma composed of
      large B-cells, in aggregate about 15-20% of all neoplasms that are sufficiently
      distinctive to recognise separately. DLBCL not otherwise specified (referred to
      henceforth as DLBCL) is a heterogeneous entity in terms of clinical presentation,
      genetic findings, response to therapy, and prognosis. A major advance was the
      application of gene expression profiling (GEP) to the study of DLBCL which
      further clarified this heterogeneity and provided a rationale for subdividing
      cases into groups. The most popular system divides cases of DLBCL according to
      cell-of-origin into germinal centre B-cell like (GCB) and activated B-cell like
      (ABC) subtypes, with about 10-15% of cases being unclassifiable. Patients with
      the GCB subtype usually have better prognosis than patients with the ABC subtype.
      Although cell-of-origin is useful for predicting outcome, the GCB and ABC
      subtypes remain heterogeneous, with better and worse prognostic subsets within
      each group. Next generation sequencing (NGS) analysis of DLBCL has facilitated
      global identification of numerous and diverse genetic abnormalities in these
      neoplasms and has shown that GCB and ABC tumours have different mutation
      profiles. Although the therapy of patients with DLBCL is an active area of
      research, the current 5-year overall survival rate is 60-70% using standard-of
      care frontline therapy. A precision medicine approach for the design of new
      therapies based on molecular findings in DLBCL is likely the best path forward.
      As pathologists, our role has expanded beyond diagnosis. We must perform a
      complete work-up of DLBCL cases. In addition to our traditional role in
      establishing the diagnosis, we need to analyse markers that provide information
      regarding prognosis and potential therapeutic targets. We also must ensure that
      adequate tissue is triaged for molecular studies which are essential for
      designing therapy regimens, particularly in the setting of disease relapse.

PMID- 29167022
TI  - Does apraxia support spatial and kinematic or mirror neuron approaches to social
      interaction? A commentary on Binder et al. (2017).

PMID- 29167023
TI  - Underlying mechanisms of mistreatment in the surgical learning environment: A
      thematic analysis of medical student perceptions.
AB  - BACKGROUND: Medical students experience more psychological distress than the
      general population. One contributing factor is mistreatment. This study aims to
      understand the mechanisms of mistreatment as perceived by medical students.
      METHODS: Students completed anonymous surveys during the first and last didactic
      session of their surgery clerkship in which they defined and gave examples of
      mistreatment. Team-based thematic analysis was performed on responses. RESULTS:
      Between January 2014 and June 2016, 240 students participated in the surgery
      clerkship. Eighty-nine percent of students completed a survey. Themes observed
      included (1) Obstruction of Students' Learning, (2) Exploitation of Student
      Vulnerability, (3) Exclusion from the Medical Team, and (4) Contextual Amplifiers
      of Mistreatment Severity. CONCLUSION: The themes observed in this study improve
      our understanding of the students' perspective on mistreatment as it relates to
      their role in the clinical learning context, which can serve as a starting point
      for interventions that ultimately improve students' experiences in the clinical
      setting.

PMID- 29167024
TI  - Evolving treatment of necrotizing pancreatitis.
AB  - BACKGROUND: Over the past decade, the treatment of necrotizing pancreatitis (NP)
      has incorporated greater use of minimally invasive techniques, including
      percutaneous drainage and endoscopic debridement. No study has yet compared
      outcomes of patients treated with all available techniques. We sought to evaluate
      the evolution of NP treatment at our high volume pancreas center. We hypothesized
      that minimally invasive techniques (medical only, percutaneous, and endoscopic)
      were used more frequently in later years. METHODS: Treatment strategy of NP
      patients at a single academic medical center between 2005 and 2014 was reviewed.
      Definitive management of pancreatic necrosis was categorized as: 1) medical
      treatment only; 2) surgical only; 3) percutaneous (interventional radiology - IR)
      only; 4) endoscopic only; and 5) combination (Surgery +/- IR +/- Endoscopy).
      RESULTS: 526 NP patients included biliary (45%), alcoholic (17%), and idiopathic
      (20%) etiology. Select patients were managed exclusively by medical, IR, or
      endoscopic treatment; use of these therapies remained relatively consistent over
      time. A combination of therapies was used in about 30% of patients. Over time,
      the percentage of NP patients managed without operation increased from 28% to
      41%. 247 (47%) of patients had operation as the only NP treatment; an additional
      143 (27%) required surgery as part of a multidisciplinary management. CONCLUSION:
      Select NP patients may be managed exclusively by medical, IR, or endoscopic
      treatment. Combination treatment is necessary in many NP patients, and surgical
      treatment continues to play an important role in the definitive therapy of
      necrotizing pancreatitis patients.

PMID- 29167025
TI  - Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a
      critical contributor to the pathogenesis of psoriasis.
AB  - Psoriasis-specific proteins dysregulated in keratinocytes and involved in the
      pathophysiological process of psoriasis remains elusive. We report here that
      epidermal galectin-3 expression is significantly downregulated in lesional skin,
      but not in non-lesional skin in psoriasis patients, nor in a group of diseases
      known as psoriasiform dermatitis clinically and histologically similar to
      psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote
      development of psoriatic lesions, as evidenced by more severe skin inflammation
      in galectin-3 knockout (gal3-/-) mice, compared to wild-type mice, after
      imiquimod treatment, and in skin from gal3-/- mice grafted onto wildtype mice.
      The development of psoriatic-like lesions is attributable to 1) the spontaneously
      tuning up of psoriasis signatures in keratinocytes through JNK pathway; and 2)
      neutrophil accumulation caused by the enhanced leukocyte-recruiting capacity
      associated with overexpression of S100A7-9 and CXCL-1, 8 in keratinocytes with
      impaired galectin-3 expression. Psoriasis-like skin inflammation is significantly
      improved in gal-3-/- mice both by inhibition of neutrophils accumulation with a
      selective CXCR2 antagonist of SB225002, and by intracutaneous injection of
      recombinant galectin-3. Overall, these findings offer promising galectin-3
      related diagnostic and therapeutic resolutions of psoriasis.

PMID- 29167026
TI  - Safety of Moderate Hypothermia With Antegrade Cerebral Perfusion in Total Aortic
      Arch Replacement.
AB  - BACKGROUND: Total aortic arch replacement (TOTAL) is a complicated operation and
      has traditionally required deep hypothermic circulatory arrest. In this study,
      the impact of moderate hypothermic circulatory arrest (MHCA) and antegrade
      cerebral perfusion (ACP) for TOTAL were examined. METHODS: The ARCH International
      aortic database was queried and 3,265 patients undergoing TOTAL using ACP were
      identified. Patients were divided into groups based on lowest cooling
      temperature: MHCA (20 degrees  to 28 degrees C) or deep hypothermia (DHCA) (12
      degrees  to 20 degrees C). Propensity-matched scoring using 15 variables was used
      in 669 matched pairs. Multivariable analyses were performed. RESULTS: In the
      unmatched cohort, more patients underwent MHCA (2,586; 79.2%) who were also
      younger (p < 0.001) and more frequently underwent emergent operations (p < 0.001)
      than DHCA patients. For the propensity-matched patients, there were significant
      differences in cardiopulmonary bypass (CPB) time (MHCA 200 minutes versus DHCA
      243 minutes, p < 0.001), aortic crossclamp time (MHCA 120 minutes versus DHCA 142
      minutes, p < 0.001), and cerebral perfusion time (MHCA 63 minutes versus DHCA 58
      minutes, p < 0.001). Of note, there was no difference in neurologic outcomes nor
      in-hospital mortality for the two temperature groups. Multivariable analysis of
      risk factors for mortality included CPB time (odds ratio [OR] 1.006; p < 0.001),
      concomitant mitral valve surgery (OR 3.070; p = 0.003), emergent operation (OR
      2.924; p < 0.001), and poor ejection fraction (OR 3.133; p = 0.011). Independent
      risk factors for stroke included coronary artery disease (OR 1.856; p < 0.001),
      cerebral vascular disease (OR 2.172; p < 0.001), emergent operation (OR 2.109; p
      < 0.001), and CPB time (OR 1.004; p < 0.001). CONCLUSIONS: In this series, TOTAL
      with MHCA and ACP can be safely performed with acceptable operative risk. MHCA
      and ACP represent an effective strategy for TOTAL and may obviate the need for
      DHCA.

PMID- 29167027
TI  - Corrigendum to "Characterization of common and rare mutations in EGFR and
      associated clinicopathological features in a large population of Chinese patients
      with lung cancer" [Pathology - Research and Practice 213 (2017) 749-758].

PMID- 29167028
TI  - Corrigendum to "Validation of a next generation sequencing panel for detection of
      hotspot cancer mutations in a clinical laboratory" [Journal information:
      Pathology-Research and Practice, 2017, Volume 213, Issue 2, Pages: 98-105].

PMID- 29167029
TI  - Intervention studies to foster resilience - A systematic review and proposal for
      a resilience framework in future intervention studies.
AB  - Psychological resilience refers to the phenomenon that many people are able to
      adapt to the challenges of life and maintain mental health despite exposure to
      adversity. This has stimulated research on training programs to foster
      psychological resilience. We evaluated concepts, methods and designs of 43
      randomized controlled trials published between 1979 and 2014 which assessed the
      efficacy of such training programs and propose standards for future intervention
      research based on recent developments in the field. We found that concepts,
      methods and designs in current resilience intervention studies are of limited use
      to properly assess efficacy of interventions to foster resilience. Major problems
      are the use of definitions of resilience as trait or a composite of resilience
      factors, the use of unsuited assessment instruments, and inappropriate study
      designs. To overcome these challenges, we propose 1) an outcome-oriented
      definition of resilience, 2) an outcome-oriented assessment of resilience as
      change in mental health in relation to stressor load, and 3) methodological
      standards for suitable study designs of future intervention studies. Our
      proposals may contribute to an improved quality of resilience intervention
      studies and may stimulate further progress in this growing research field.

PMID- 29167030
TI  - Comparison of bronchodilator administration with vibrating mesh nebulizer and
      standard jet nebulizer in the emergency department.
AB  - INTRODUCTION: Projects comparing bronchodilator response by aerosol devices in
      the ED are limited. Evidence suggests that the vibrating mesh nebulizer (VMN)
      provides 5-fold greater aerosol delivery to the lung as compared to a jet
      nebulizer (JN). The aim of this project was to evaluate a new nebulizer deployed
      in an Emergency Department. METHODS: A quality improvement evaluation using a
      prospectively identified data set from the electronic medical record comparing
      all ED patients receiving aerosolized bronchodilators with the JN during
      September 2015 to those receiving aerosolized bronchodilators with the VMN during
      October 2015. RESULTS: 1594 records were extracted, 879 patients received
      bronchodilators via JN and 715 patients via the VMN. Admission rates in the VMN
      group were 28.1% and in the JN group at 41.4%. The total albuterol dose
      administered was significantly lower in the VMN group compared to the JN
      (p<0.001). No patient in the VMN group required >5mg albuterol to control
      symptoms (85% of the VMN group received only 2.5mg) whereas dosing in the JN
      group was higher in some patients (with 47% receiving only 2.5mg). The use of VMN
      was also associated with a 13% (37min) reduction in median length of stay in the
      ED. CONCLUSIONS: The VMN was associated with fewer admissions to the hospital,
      shorter length of stay in the ED and a reduction in albuterol dose. The device
      type was a predictor of discharge, disposition and amount of drug used.
      Randomized controlled studies are needed to corroborate these findings.

PMID- 29167031
TI  - Vaccination coverage in patients affected by chronic diseases: A 2014 cross
      sectional study among subjects hospitalized at Bari Policlinico General Hospital.
AB  - Subjects affected by at least 1 chronic disease are the target of influenza
      vaccination strategies because they are at high risk of influenza complications
      or death. The aim of this cross-sectional study is to evaluate flu and
      pneumococcal vaccination coverage (VC) in a sample of patients hospitalized at
      Bari Policlinico General Hospital (South Italy). According to national public
      health guidelines, these patients should have been vaccinated at hospital
      discharge by general practitioners. There were 540 patients involved in the
      study, and the average age was of 46.9 +/- 13.4 years (range, 0-64 years). We
      assessed the vaccination status of 412 of 540 (76.3%) patients. The overall VC
      was 22.8% (94/412) for influenza and 7.2% (30/412) for pneumococcal vaccine.
      Doctor recommendation has a pivotal importance in vaccine acceptance, and recent
      experiences seem to show a high efficacy of the vaccination offer during
      hospitalization. This model could be helpful to improve influenza and
      pneumococcal vaccination offers to patient with underlying chronic conditions.

PMID- 29167032
TI  - Using the Evidence-Based Practice Service Nursing Bundle to Increase Patient
      Satisfaction.
AB  - ABSTRACTINTRODUCTION: Patient satisfaction and patient experience goals are often
      linked to financial consequences. Although the link does exist, the bottom line
      is not only about money; it's about providing a quality experience for ED
      patients and creating an environment that engages staff. Evidence-based practice
      (EBP) strategies that have positive impact on patient perceptions of their ED
      care and increased satisfaction ratings include AIDET, Hourly Rounding, and
      Bedside Shift Report, which incorporate updates of test results and explanations
      of events occurring during a patient's visit. In addition to these outcomes,
      Hourly Rounding and Bedside Shift Report have been linked to patient safety
      improvements. Combining these strategies, our team created and implemented the
      service nursing bundle as a quality improvement (QI) initiative, with the goal of
      having a positive effect on patient experiences in emergency departments,
      represented by at least a 5% increase in overall quality-of-care ranking and
      ratings. METHODS: This QI project involved comparing professional research
      consultant (PRC) patient- satisfaction phone survey ratings from patients before
      and after ED staff members completed a 1-hour service nursing bundle class. In
      addition to the patient-satisfaction ratings, 1,104 audits evaluating staff use
      of the service bundle implementation were collected over an 8-week period.reading
      document: RESULTS: The random observational audits showed the adoption of the
      service nursing bundle as staff compliance started at 65% in week 1 compared with
      100% by week 8. Before intervention (July 2015): 50% of patients rated their
      overall quality of care as excellent, yielding a benchmark ranking of 42.5
      percentile. Postservice bundle education implementation (September 2015): 60% of
      patients rated their overall quality of care as excellent, increasing our ranking
      to the 85.5 percentile. The postservice bundle group was 1.5 times more likely to
      respond "excellent" to all 5 survey questions, which was statistically
      significant (z =2.82, P = 0.004). The patients' perceptions of total time spent
      in the emergency department and ratings of "excellent" revealed a significant
      statistical difference (before: 35.0%, after: 49.5%, X2 (1) = 4.24, P < 0.05).
      DISCUSSION: With the implementation of the bundle, our emergency department
      experienced an 11.8% increase in the number of patients rating their overall
      quality of care as excellent. This upsurge resulted in a 40% increase in overall
      quality of care, propelling our emergency department's ranking to the 85th
      percentile.

PMID- 29167033
TI  - Nursing Perceptions of the Emergency Severity Index as a Triage Tool in the
      United Arab Emirates: A Qualitative Analysis.
AB  - INTRODUCTION: With emergency department crowding becoming an increasing problem
      across the globe, nursing triage to prioritize patients receiving care is ever
      more important. ESI is the most common triage system used in the United States
      and is increasingly used worldwide. This qualitative study that explores
      emergency nursing perceptions of the ESI identifies strengths, weaknesses, and
      barriers to implementation of the ESI internationally. METHODS: We conducted a
      cross-sectional qualitative analysis using semistructured interviews of 27
      emergency triage nurses. Content analysis was performed by 2 independent coders,
      using NVivo software to identify and analyze important themes. RESULTS: Interview
      coding revealed 7 core themes related to use of the ESI (frequencies indicated in
      parentheses): ease of use (90), speed and efficiency (135), patient safety (12),
      accuracy and reliability (30), challenging patient characteristics (123),
      subjectivity and variability (173), and effect of triage system on team dynamics
      (100). Intercoder agreement was excellent (Cohen's unweighted kappa = 0.84).
      Subjectivity and variability in ESI score assignment consistently emerged in all
      interviews and included variability in number and use of resources, definition of
      "high risk," nursing experience, and subjectivity in pain assessment. DISCUSSION:
      Although emergency nurses perceive the ESI as easy to use, there are concerns
      about the subjectivity and variability inherent in the ESI that can lead to a
      functional lack of triage and a burden of undifferentiated ESI level 3 patients.
      These limitations in separating critically ill patients and in stratifying
      patients based on anticipated required resources points to the need for
      improvement in the ESI algorithm or a more objective triage system that can
      predict patient outcomes.

PMID- 29167034
TI  - Body awareness training in the treatment of wearing-off related anxiety in
      patients with Parkinson's disease: Results from a pilot randomized controlled
      trial.
AB  - BACKGROUND: In Parkinson's disease (PD) patients, fluctuations in symptoms
      commonly occur after many years of dopamine replacement therapy. The so-called
      wearing-off phenomenon exists of both motor and non-motor symptoms, such as
      rigidity and anxiety. Current treatment options are limited and an integrated
      approach is needed to address the complex interactions between motor and non
      motor symptoms. Since wearing-off is eventually inevitable, treatment needs to
      focus on coping, acceptance and self-efficacy. We developed the body awareness
      training, named BEWARE, combining physical therapy with acceptance and commitment
      therapy to help PD patients deal better with wearing-off related anxiety (WRA).
      METHODS: This was an investigator-blinded randomized controlled trial. Forty PD
      patients with WRA were randomly assigned to the BEWARE or to the treatment as
      usual (TAU) condition. Assessments were performed prior to and immediately after
      the treatment period, and at 3-months follow up. The primary outcome was self
      efficacy, secondary outcomes focused on mobility, daily functioning, anxiety,
      depression and quality of life. RESULTS: There was no significant improvement in
      self-efficacy in the BEWARE treatment condition when compared to TAU. However,
      standing balance and emotional wellbeing showed a significant improvement, and
      feelings of stigmatization showed a trend-significant decrease in the BEWARE
      condition. CONCLUSIONS: We consider the BEWARE training to be a promising
      therapeutic approach to address WRA. Improvement points from the participants
      included 1) less frequent but longer therapy sessions; 2) active involvement of
      caregivers; and 3) the development of a supportive workbook. The optimized
      treatment protocol needs further evaluation in a phase III RCT. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT02054845.

PMID- 29167035
TI  - Promoting empathy among medical students: A two-site randomized controlled study.
AB  - OBJECTIVE: To assess the effects of Balint groups on empathy measured by the
      Consultation And Relational Empathy Measure (CARE) scale rated by standardized
      patients during objective structured clinical examination and self-rated
      Jefferson's School Empathy Scale - Medical Student (JSPE-MS(c)) among fourth-year
      medical students. METHODS: A two-site randomized controlled trial were planned,
      from October 2015 to December 2015 at Paris Diderot and Paris Descartes
      University, France. Eligible students were fourth-year students who gave their
      consent to participate. Participants were allocated in equal proportion to the
      intervention group or to the control group. Participants in the intervention
      group received a training of 7 sessions of 1.5-hour Balint groups, over 3months.
      The main outcomes were CARE and the JSPE-MS(c) scores at follow-up. RESULTS: Data
      from 299 out of 352 randomized participants were analyzed: 155 in the
      intervention group and 144 in the control group, with no differences in baseline
      measures. There was no significant difference in CARE score at follow-up between
      the two groups (P=0.49). The intervention group displayed significantly higher
      JSPE-MS(c) score at follow-up than the control group [Mean (SD): 111.9 (10.6)
      versus 107.7 (12.7), P=0.002]. The JSPE-MS(c) score increased from baseline to
      follow-up in the intervention group, whereas it decreased in the control group
      [1.5 (9.1) versus -1.8 (10.8), P=0.006]. CONCLUSIONS: Balint groups may
      contribute to promote clinical empathy among medical students. TRIAL
      REGISTRATION: NCT02681380.

PMID- 29167036
TI  - Inverse association between hyperthymic affective temperament and coronary
      atherosclerosis: A coronary computed tomography angiography study.
AB  - OBJECTIVE: A bidirectional relationship exists between psychiatric disorders and
      cardiovascular diseases, however less is known with regards to personality
      traits. Accumulating data suggest that affective temperaments are both associated
      with psychiatric and somatic diseases. The aim of our study was to evaluate the
      associations between different affective temperaments and the presence of
      coronary atherosclerosis. METHODS: 200 consecutive patients referred to coronary
      computed tomography angiography (CCTA) due to suspected coronary artery disease
      (CAD) were included in our study. Medical history and demographic parameters were
      recorded and all patients completed the Temperament Evaluation of Memphis, Pisa,
      Paris, and San Diego Autoquestionnaire (TEMPS-A) and the Beck Depression
      Inventory (BDI). The presence of coronary artery disease was evaluated based on
      the CCTA images. RESULTS: 39 patients were free of any coronary atherosclerosis
      (CCTA-) and 161 had coronary atherosclerosis (CCTA+). Hyperthymic affective
      temperament score was higher in CCTA- subjects as compared to CCTA+ (13.1+/-3.0
      vs 11.5+/-4.6, p=0.010, respectively). Hyperthymic affective temperament score
      showed a significant independent, inverse relationship with coronary
      atherosclerosis (OR: 0.91 CI: 0.82-0.99, p=0.04). CONCLUSION: Our results suggest
      that hyperthymic affective temperament is independently associated with the
      absence of CAD. It requires further research to delineate the mechanism mediating
      the effect of hyperthymia on better coronary artery health and establishing
      potential biochemical or behavioral factors, both of which could be exploited for
      prevention and treatment purposes. But it is plausible, that the evaluation of
      affective temperaments have importance both in relation with psychiatric and
      cardiovascular disorders.

PMID- 29167037
TI  - The burden of suicidal ideation among persons with type II diabetes: A scoping
      review.
AB  - OBJECTIVE: Diabetes is a major global health concern. People with diabetes have
      worse mental health outcomes than those without diabetes. Researchers have
      recently sought to examine the relationship between diabetes and suicidal
      ideation. The aim of this study is to determine the burden of suicidal ideation
      among adults with type II diabetes from existing literature. METHODS: We
      conducted a scoping review of published literature in PubMed, PsycINFO, CINAHL,
      Web of Science, and Google Scholar published before March 2017. To identify
      relevant literature, search terms included suicidal ideation and type II
      diabetes. The search was limited to English language peer-reviewed journal
      articles. The main outcome of interest was suicidal ideation captured on a
      validated scale in a population with type II diabetes. RESULTS: This review
      resulted in 10 relevant studies, which reported the prevalence of suicidal
      ideation ranging from 2.5-51.4% with a median prevalence of 18.6% among adults
      with diabetes. Across the five studies reporting the associated risks, all but
      one study found a significant risk for persons with diabetes to endorse suicidal
      ideation and only three studies adjusted for depression. CONCLUSIONS: This review
      demonstrates the need for future studies to investigate potential mechanistic
      pathways of suicidality among persons with diabetes.

PMID- 29167038
TI  - Oral contraceptives positively affect mood in healthy PMS-free women: A
      longitudinal study.
AB  - OBJECTIVE: Menstrual cycle phase and oral contraceptives (OC) use influence mood
      and cognition and these effects may be moderated by the mineralocorticoid
      receptor (MR) genotype. The effect of menstrual cycle phase on mood may be
      increased if participants know that this is the focus of study. We assessed
      aspects associated with reproductive depression such as mood, interpersonal
      sensitivity, affect lability and depressive cognitions in MR-genotyped OC-users
      and naturally cycling (NC) women in a carefully masked design. METHODS: A
      homogenous sample of healthy, PMS-free, pre-menopausal MR-genotyped women (n=92)
      completed online questionnaires eight times during two consecutive cycles.
      RESULTS: The masking of the research question was successful. OC-users did not
      differ significantly from NC women in positive and negative affect at the time of
      assessment, personality characteristics (e.g. neuroticism) or mental and physical
      health. Both groups reported more shifts in anger in the first cycle week
      (p<0.001; etap2=0.08). Compared to NC women, OC-users reported fewer mood-shifts
      between depression and elation in the mid-luteal phase of the menstrual cycle
      (p=0.002; etap2=0.10) and had fewer ruminating thoughts at all phases (p=0.003;
      etap2=0.11). Effects of MR-genotype were not significant after correction for
      multiple comparisons. CONCLUSION: OC users scored more favorably on measures
      associated with reproductive depression. OC users also showed a decreased affect
      variability possibly indicating an emotional blunting effect, which is in line
      with previous reports on affect-stabilizing effects of OC. Limitations were loss
      of cases due to irregularities in the menstrual cycle length and possible
      confounding by the 'survivor effect', since almost all OC-users took OC for more
      than a year.

PMID- 29167039
TI  - Psychological and psychiatric symptoms of terminally ill patients with cancer and
      their family caregivers in the home-care setting: A nation-wide survey from the
      perspective of bereaved family members in Japan.
AB  - OBJECTIVE: The psychological and psychiatric symptoms of terminally ill cancer
      patients are highly problematic and have been associated with greater burden
      among caregivers. Until now, the extent of these problems in the home care
      setting was unclear. METHODS: This retrospective study was conducted as part of a
      nationwide survey from the perspective of bereaved family members in Japan (J
      HOPE3). The bereaved family members rated the symptoms of delirium and suicidal
      ideation of patients with cancer, and the sleeplessness and depressed mood of
      family caregivers utilizing home care services in the one month before the
      patients' deaths. Regression analyses were performed to identify factors
      associated with caregivers' sleeplessness or depressed mood. RESULTS: Of the 532
      subjects analyzed, between 17% and 65% of patients experienced various symptoms
      of delirium, and 27% suicidal ideation. Among family caregivers, 60% experienced
      sleeplessness and 35% experienced depressed mood at least once during the week.
      Caregivers' psychological symptoms were associated with their own poor health
      status, being the spouse of the patient, and the patients' psychological or
      psychiatric symptoms. To manage patients' symptoms, 11% of caregivers had
      consulted psychiatrists or psychologists while another 11% wanted to do so.
      CONCLUSION: Psychological problems assessed were common among patients with
      cancer and their family caregivers in the one month of home care prior to the
      patient's death. An effective complementary care system, run by home-visit
      physicians, nurses, and experts in mental disorders, is needed.

PMID- 29167040
TI  - Delirium in the intensive care setting and the Richmond Agitation and Sedation
      Scale (RASS): Drowsiness increases the risk and is subthreshold for delirium.
AB  - INTRODUCTION: Sedation is a core concept in the intensive care setting, however,
      the impact of sedation on delirium has not yet been studied to date. METHODS: In
      this prospective cohort study, 225 patients with Richmond Agitation and Sedation
      (RASS) scores of -1 - drowsiness and 0 - alert- and calmness were assessed with
      the Delirium Rating Scale-Revised 1998 (DRS-R-98) and DSM-IV-TR-determined
      diagnosis of delirium assessing drowsiness versus alertness. RESULTS: By itself,
      drowsiness increased the odds for developing delirium eightfold (OR 7.88 p<0.001)
      and rates of delirium were 68.2 and 21.4%, respectively. Further, in the drowsy
      patient, delirium was more severe. In the presence of drowsiness, delirium was
      characterized by sleep-wake cycle disturbances and language abnormalities. These
      two features, in addition to psychomotor retardation, allowed the correct
      classification of delirium at RASS-1. The same features, in addition to thought
      abnormalities and the impairment in the cognitive domain, orientation, attention,
      short- and long-term memory representing the core domains of delirium, or the
      temporal onset were very sensitive towards delirium, however lacked specificity.
      Conversely, delusions, perceptual abnormalities and lability of affect
      representing the non-core domain were very specific for delirium in the drowsy,
      however, not very sensitive. In the absence of delirium, drowsiness caused
      attentional impairment and language abnormalities. CONCLUSION: Drowsiness
      increased the odds for developing delirium eightfold and caused more severe
      delirium, which was characterized by sleep-wake cycle and language abnormalities.
      Further, drowsiness by itself caused attentional impairment and language
      abnormalities, thus, with its disturbance in consciousness was subthreshold for
      delirium.

PMID- 29167041
TI  - Efficacy of an internet-based cognitive behavioral stress management training in
      women with idiopathic preterm labor: A randomized controlled intervention study.
AB  - OBJECTIVE: This randomized controlled trial aimed at evaluating the efficacy of
      an internet-based cognitive behavioral stress management program (IB-CBSM) for
      pregnant women with preterm labor (PTL) on birth outcome and stress-related
      psychological and biological parameters. METHODS: 93 pregnant women with PTL
      (gestational age 18-32) were assigned to either the IB-CBSM (n=50) or a control
      group (CG) based on distraction (n=43). Participants in both groups worked
      through six weekly modules. Birth outcome measures included gestational age,
      neonatal weight and length at birth and the rate of preterm birth (PTB).
      Questionnaires assessed psychological wellbeing and the activity of the HPA-axis
      was measured with the cortisol awakening reaction (CAR), both before (T1) and
      after the intervention (T2). RESULTS: Birth outcome and psychological wellbeing
      did not differ between IB-CBSM and CG. However, psychological wellbeing was
      higher after both interventions (PSS: etap2=0.455, STAIX1: etap2=0.455, STAIX2:
      etap2=0.936, PRAT: etap2=0.465, EPDS: etap2=0.856). Cortisol levels were stable
      and did not alter differently between groups from T1 to T2. Higher cortisol
      levels were associated with lower gestational age at birth, whereas no
      significant correlations were found between weight and length at birth.
      CONCLUSIONS: Although there were no significant differences between the two
      groups and birth outcome, psychological and biological parameters, both
      interventions (CBSM and CG) showed equivalent effects and proved to be beneficial
      with regard to psychosocial distress and well-being. Further research is needed
      to investigate CBSM and distraction interventions for pregnant women at risk for
      PTB together with a non-intervention control condition.

PMID- 29167042
TI  - Classifying post-stroke fatigue: Optimal cut-off on the Fatigue Assessment Scale.
AB  - OBJECTIVE: Post-stroke fatigue is common and has debilitating effects on
      independence and quality of life. The Fatigue Assessment Scale (FAS) is a valid
      screening tool for fatigue after stroke, but there is no established cut-off. We
      sought to identify the optimal cut-off for classifying post-stroke fatigue on the
      FAS. METHODS: In retrospective analysis of two independent datasets (the '2015'
      and '2007' studies), we evaluated the predictive validity of FAS score against a
      case definition of fatigue (the criterion standard). Area under the curve (AUC)
      and sensitivity and specificity at the optimal cut-off were established in the
      larger 2015 dataset (n=126), and then independently validated in the 2007 dataset
      (n=52). RESULTS: In the 2015 dataset, AUC was 0.78 (95% CI 0.70-0.86), with the
      optimal >=24 cut-off giving a sensitivity of 0.82 and specificity of 0.66. The
      2007 dataset had an AUC of 0.83 (95% CI 0.71-0.94), and applying the >=24 cut-off
      gave a sensitivity of 0.84 and specificity of 0.67. Post-hoc analysis of the 2015
      dataset revealed that using only the 3 most predictive FAS items together ('FAS
      3') also yielded good validity: AUC 0.81 (95% CI 0.73-0.89), with sensitivity of
      0.83 and specificity of 0.75 at the optimal >=8 cut-off. CONCLUSION: We propose
      >=24 as a cut-off for classifying post-stroke fatigue on the FAS. While further
      validation work is needed, this is a positive step towards a coherent approach to
      reporting fatigue prevalence using the FAS.

PMID- 29167043
TI  - Exposure to teasing on popular television shows and associations with adolescent
      body satisfaction.
AB  - OBJECTIVE: This study uses a novel mixed methods design to examine the
      relationship between incidents of teasing in popular television shows and body
      satisfaction of adolescent viewers. METHODS: Survey data were used to identify 25
      favorite television shows in a large population-based sample of Minnesota
      adolescents (N=2793, age=14.4years). Data from content analysis of teasing
      incidents in popular shows were linked to adolescent survey data. Linear
      regression models examined associations between exposure to on-screen teasing in
      adolescents' own favorite shows and their body satisfaction. Effect modification
      by adolescent weight status was tested using interaction terms. RESULTS: Teasing
      on TV was common, with 3.3 incidents per episode; over one-quarter of teasing was
      weight/shape-related. Exposure to weight/shape-related teasing (beta=-0.43,
      p=0.008) and teasing with overweight targets (beta=-0.03, p=0.02) was inversely
      associated with girls' body satisfaction; no associations were found for boys.
      Findings were similar regardless of the adolescent viewer's weight status.
      CONCLUSIONS: Families, health care providers, media literacy programs and the
      entertainment industry are encouraged to consider the negative effects exposure
      to weight stigmatization can have on adolescent girls.

PMID- 29167044
TI  - Psychological stress declines rapidly from age 50 in the United States: Yet
      another well-being paradox.
AB  - OBJECTIVES: Although there is evidence that evaluative subjective well-being
      (e.g., life satisfaction) shows a U-shaped pattern with highest satisfaction in
      the youngest and oldest years and lowest in the middle years of adulthood, much
      less is known about experiential well-being. We explore a negative indicator of
      experiential well-being (perceived stress), examine its association with age, and
      explore possible determinants of the age pattern. METHODS: Using Gallup
      Healthways survey data of over 1.5 million U.S. respondents, we analyzed a
      question asking about stress yesterday and demographic determinants of the
      pattern. To confirm this pattern, data on stress was analyzed from the American
      Time Use Survey and data on distress was analyzed from the Health and Retirement
      Survey. RESULTS: We show that ratings of daily, perceived stressfulness yield a
      paradox, with high levels from the 20's through about age 50, followed by a
      precipitous decline through the 70's. Data from the other two surveys confirmed
      the age pattern for stress. Regressions with the Gallup-Healthways data
      statistically controlled several third-variables, yet none substantially altered
      the pattern. CONCLUSION: We argue that this new experiential well-being pattern
      informs us about aging in the US and the "paradox" calls out for explanation.

PMID- 29167045
TI  - Long-term caregiving is associated with impaired cardiovagal baroreflex.
AB  - OBJECTIVE: Caregiving stress is associated with increased risk of cardiovascular
      disease (CVD). Inability to adequately regulate blood pressure is a possible
      underlying mechanism explaining this risk. We examined the relationship between
      length of caregiving and cardiovagal baroreflex sensitivity (cBRS) to better
      understand the link between caregiving and CVD risk. METHODS: A total of 146
      elderly individuals (>=55years) participated in this study, of whom 96 were
      providing in-home care to a spouse with dementia and 50 were healthy controls
      married to a non-demented spouse (i.e., non-caregivers). Among the caregivers, 56
      were short-term caregivers (caring<4years) and 40 were long-term caregivers
      (caring>=4years). A multiple linear regression model, with contrast codes
      comparing short and long-term caregivers with non-caregivers was used to
      understand relationships between chronic caregiving and cBRS. RESULTS: After
      controlling for relevant demographic and health characteristics, mean+/-SE log
      transformed cBRS for non-caregivers was 0.971+/-0.029. Relative to non
      caregivers, the long-term caregivers had significantly impaired cBRS (0.860+/
      0.033; p=0.013). However, mean cBRS for short-term caregivers did not significant
      differ from non-caregivers (0.911+/-0.028; p=0.144). CONCLUSION: These results
      suggest that long-term caregiving stress is associated with an impaired cBRS.
      Accumulation of stress from years of caregiving could result in worse cBRS
      function, which could be a mechanistic explanation for the correlation between
      caregiving stress and the increased risk of CVD.

PMID- 29167046
TI  - Changes in Allostatic Load during workplace reorganization.
AB  - OBJECTIVE: Allostatic Load (AL) represents the strain on the body produced by
      repeated physiologic or allostatic responses activated during stressful
      situations. Several cross-sectional studies have found empirical substantiation
      for the relationship between impaired psychosocial work environment and high AL.
      The aim of this longitudinal study is to investigate changes in AL during
      workplace reorganization that has been shown to cause impaired psychosocial work
      environment. Moreover, we aim to investigate the association between changes in
      AL and changes in psychosocial work environment (job strain, effort-reward
      imbalance) and psychological distress (stress symptoms and perceived stress).
      METHODS: A major reorganization of non-state public offices was effectuated in
      Denmark on 1 January 2007. In 2006 and 2008, we collected clinical and
      questionnaire data from 359 participants, 265 women and 94 men, employed in seven
      municipality or county administrations. Four municipalities and one county merged
      with others, while one municipality and one county remained unmerged. We
      calculated the AL score based on 13 physiological markers reflecting stress
      responses of the cardiovascular, metabolic, neuroendocrine and immune systems. We
      analysed changes in AL from 2006 to 2008. RESULTS: AL increased significantly
      during workplace reorganization in the whole study group but we observed only a
      tendency of significant increase in AL in the merger group compared with the
      control group. Moreover, we observed no association between the changes in AL and
      changes in psychosocial work environment and psychological distress. CONCLUSIONS:
      This result leaves the conclusion unclear but contributes to the limited research
      in this area with a longitudinal design and focus on low-risk levels and small
      changes in AL in healthy people as predictor of future disease.

PMID- 29167047
TI  - Systematic review of measurement properties of questionnaires measuring
      somatization in primary care patients.
AB  - OBJECTIVE: The aim of this review is to critically appraise the evidence on
      measurement properties of self-report questionnaires measuring somatization in
      adult primary care patients and to provide recommendations about which
      questionnaires are most useful for this purpose. METHODS: We assessed the
      methodological quality of included studies using the COnsensus-based Standards
      for the selection of health Measurement INstruments (COSMIN) checklist. To draw
      overall conclusions about the quality of the questionnaires, we conducted an
      evidence synthesis using predefined criteria for judging the measurement
      properties. RESULTS: We found 24 articles on 9 questionnaires. Studies on the
      Patient Health Questionnaire-15 (PHQ-15) and the Four-Dimensional Symptom
      Questionnaire (4DSQ) somatization subscale prevailed and covered the broadest
      range of measurement properties. These questionnaires had the best internal
      consistency, test-retest reliability, structural validity, and construct
      validity. The PHQ-15 also had good criterion validity, whereas the 4DSQ
      somatization subscale was validated in several languages. The Bodily Distress
      Syndrome (BDS) checklist had good internal consistency and structural validity.
      Some evidence was found for good construct validity and criterion validity of the
      Physical Symptom Checklist (PSC-51) and good construct validity of the Symptom
      Check-List (SCL-90-R) somatization subscale. However, these three questionnaires
      were only studied in a small number of primary care studies. CONCLUSION: Based on
      our findings, we recommend the use of either the PHQ-15 or 4DSQ somatization
      subscale for somatization in primary care. Other questionnaires, such as the BDS
      checklist, PSC-51 and the SCL-90-R somatization subscale show promising results
      but have not been studied extensively in primary care.

PMID- 29167048
TI  - Prevalence and risk factors of excessive daytime sleepiness in insomnia
      sufferers: A study with 1311 individuals.
AB  - BACKGROUND: Several studies have investigated the prevalence and risk factors of
      excessive daytime sleepiness in the general population. However, few studies have
      investigated these in the particular subpopulation of insomnia sufferers. Thus,
      the aim of this study was to examine the prevalence and risk factors of excessive
      daytime sleepiness in a large sample of insomnia sufferers. METHODS: Data from
      1311 insomnia sufferers with age>=18years and recruited from the research
      database of the sleep laboratory of the Erasme Hospital were analysed. A score>10
      on the Epworth scale was used as the cut-off score for excessive daytime
      sleepiness. Logistic regression analyses were conducted to examine clinical and
      demographic risk factors of excessive daytime sleepiness in insomnia sufferers.
      RESULTS: The prevalence of excessive daytime sleepiness in our sample was 45.61%.
      Multivariate logistic regression analysis revealed that non-use of Z-drugs, non
      use of Trazodone alone or in combination, body mass index>=25 & <30kg/m2, body
      mass index>=30kg/m2, age>=18 & <40years, age>=40 & <65years, Beck depression
      inventory score>=5 & <16, Beck depression inventory score>=16, apnea-hypopnea
      index>=15/h, and use of selective serotonin reuptake inhibitors were significant
      risk factors of excessive daytime sleepiness in the subpopulation of insomnia
      sufferers. CONCLUSION: Excessive daytime sleepiness is a common complaint for
      individuals with insomnia. In this subpopulation, most of the risk factors for
      excessive daytime sleepiness are reversible, which justifies better management of
      this complaint to avoid its negative consequences.

PMID- 29167049
TI  - Does the presence of multiple sclerosis impact on symptom profile in depressed
      patients?
AB  - OBJECTIVE: Major depressive disorder (MDD) is common in patients with multiple
      sclerosis (MS) but may remain unrecognized because of overlapping symptoms and
      different presentation due to its specific MS-related neurobiological aetiology.
      We aimed to investigate the clinical profile of MDD in MS. METHODS: In a sample
      of MDD patients with MS (n=83) and without MS (n=782), MDD characteristics, 30
      depressive symptoms, and sum scores of cognitive, somatic, atypical and
      melancholic symptom clusters were compared using logistic regression analyses and
      analysis of co-variance. RESULTS: MDD in MS was characterized by older age of
      onset (p<0.001), and fewer comorbid anxiety disorders (37% versus 72%; p<0.001).
      The symptom 'future pessimism' was more common in MS patients (OR=1.62;
      95%CI=1.02-2.59). 'Diminished capacity for pleasure/enjoyment' (OR=0.44;
      95%CI=0.24-0.78), 'increased appetite' (OR=0.40; 95%CI=0.19-0.85), 'arousal
      symptoms' (OR=0.49; 95%CI=0.28-0.84), and 'panic/phobic symptoms' (OR=0.49;
      95%CI=0.29-0.84) were less common in MS patients. Twenty-five symptoms (83%) out
      of 30, including depression's core symptoms (sadness and loss of interest) were
      not differentially associated with MS and no differences existed for the symptom
      clusters. CONCLUSION: Only subtle differences in depressive symptom profiles
      existed between MDD patients with and without MS. The clinical profile of
      depression remains valid among MS patients, although it presents with diminished
      anxiety distress and comorbidity.

PMID- 29167050
TI  - Insecure attachment style and cumulative traumatic life events in patients with
      somatoform pain disorder: A cross-sectional study.
AB  - OBJECTIVE: Current models assume somatoform pain disorder (SPD) to be the result
      of a complex interaction between bio- and psychosocial factors, but the etiology
      is still not well understood. This study aimed to investigate the distribution of
      attachment style and the frequency of traumatic life events, especially childhood
      adversities, in patients with SPD compared to healthy controls. METHODS: We
      compared 65 patients with SPD (confirmed by Structured Clinical Interview, SCID
      I) to 65 age- and gender-matched healthy controls. The following questionnaires
      were employed: Relationship Scale Questionnaire (RSQ), Essen Trauma Inventory
      (ETI), Childhood Trauma Questionnaire (CTQ) and Patient Health Questionnaire (PHQ
      15). A logistic regression analysis was used to identify the association between
      SPD and psychological factors. RESULTS: Insecure attachment was significantly
      more prevalent (60%) in patients with SPD compared to healthy subjects (14%;
      p<0.001). Overall, 70.4% of patients with SPD reported three or more traumatic
      events in their life, compared with healthy subjects who reported predominantly
      one (40%). Patients with SPD scored significantly higher in all CTQ subscales
      compared to the healthy controls. The factor most strongly related with SPD was
      the insecure attachment style (OR=11.20, 95% CI: 1.32-94.86). Other significant
      predictive factors were depression (OR=3.35, 95% CI: 1.84-6.11) and number of
      traumatic events (OR=2.04, 95% CI: 1.06-3.92). Insecure attachment, depression
      symptoms and the number of traumatic events explained 86.2% of the variance.
      CONCLUSIONS: The high predictive value of insecure attachment style and
      cumulative traumatic events emphasize their importance as risk factors of SPD.

PMID- 29167051
TI  - Discrimination and anger control as pathways linking socioeconomic disadvantage
      to allostatic load in midlife.
AB  - OBJECTIVE: Recent evidence suggests that experiences of discrimination contribute
      to socioeconomic status health disparities. The current study examined if the
      experience and regulation of anger-an expected emotional response to
      discrimination-serves as an explanatory factor for the previously documented
      links between socioeconomic disadvantage (SED), discrimination, and allostatic
      load. METHODS: Data were drawn from the second wave of the Midlife in the United
      States (MIDUS) study and included 909 adults who participated in the biomarkers
      subproject. RESULTS: Results revealed that perceived discrimination was
      associated with higher levels of allostatic load. Furthermore, we found evidence
      that perceived discrimination and anger control sequentially explained the
      relationship between SED and allostatic load, such that greater discrimination
      was associated with lower levels of anger control, which, in turn accounted for
      the effects of discrimination on allostatic load. These results remained
      significant after controlling for negative affect, positive affect, other forms
      of anger expression, as well as demographic covariates. CONCLUSIONS: Our findings
      suggest that low anger control may be an important psychological pathway through
      which experiences of discrimination influence health.

PMID- 29167052
TI  - The impact of exposure-based cognitive behavior therapy for severe health anxiety
      on self-rated health: Results from a randomized trial.
AB  - OBJECTIVE: Self-rated health (SRH) has been shown to be a stable predictor of
      illness and mortality. Improvement in SRH, even in the absence of change in
      objective health, predicts better health and reduced mortality. Severe health
      anxiety (SHA) is characterized by fear of illness and distorted health
      perception. The objective of the present study was to investigate if exposure
      based cognitive behavior therapy (CBT) for SHA can lead to improvement in SRH and
      whether this improvement is mediated by reduced health anxiety. METHODS: Data
      were collected from a randomized controlled trial where participants with SHA
      were allocated to 12weeks of exposure-based CBT (n=99) for SHA or to a no
      treatment control condition (n=33). The mediation analysis was based on SRH- and
      health anxiety data collected weekly during the treatment phase. RESULTS: Linear
      mixed effects models analysis showed a significant interaction effect of group
      and time indicating superior improvements in SRH in exposure-based CBT compared
      to the control condition (Z=2.69, p=0.007). The controlled effect size was
      moderately large (d=0.64) and improvements were stable at 1-year follow-up.
      Reduced health anxiety was a significant mediator of improvement in SRH.
      CONCLUSIONS: 12weeks of exposure-based CBT for SHA can lead to significant
      improvements in SRH. Considering the previously established importance of SRH as
      a predictor for disease and mortality, exposure-based CBT for severe health
      anxiety may lead to improvements on several important health parameters, possibly
      even increasing the likelihood of longevity.

PMID- 29167053
TI  - Autonomic nervous system function, activity patterns, and sleep after physical or
      cognitive challenge in people with chronic fatigue syndrome.
AB  - OBJECTIVE: To explore changes in autonomic functioning, sleep, and physical
      activity during a post-exertional symptom exacerbation induced by physical or
      cognitive challenge in participants with chronic fatigue syndrome (CFS). METHODS:
      Thirty-five participants with CFS reported fatigue levels 24-h before,
      immediately before, immediately after, and 24-h after the completion of
      previously characterised physical (stationary cycling) or cognitive (simulated
      driving) challenges. Participants also provided ratings of their sleep quality
      and sleep duration for the night before, and after, the challenge. Continuous
      ambulatory electrocardiography (ECG) and physical activity was recorded from 24-h
      prior, until 24-h after, the challenge. Heart rate (HR) and HR variability (HRV,
      as high frequency power in normalized units) was derived from the ECG trace for
      periods of wake and sleep. RESULTS: Both physical and cognitive challenges
      induced an immediate exacerbation of the fatigue state (p<0.001), which remained
      elevated 24-h post-challenge. After completing the challenges, participants spent
      a greater proportion of wakeful hours lying down (p=0.024), but did not
      experience significant changes in sleep quality or sleep duration. Although the
      normal changes in HR and HRV during the transition from wakefulness to sleep were
      evident, the magnitude of the increase in HRV was significantly lower after
      completing the challenge (p=0.016). CONCLUSION: Preliminary evidence of reduced
      nocturnal parasympathetic activity, and increased periods of inactivity, were
      found during post-exertional fatigue in a well-defined group of participants with
      CFS. Larger studies employing challenge paradigms are warranted to further
      explore the underlying pathophysiological mechanisms of post-exertional fatigue
      in CFS.

PMID- 29167054
TI  - Cerebral gray matter changes in persistent postural perceptual dizziness.
AB  - BACKGROUND: Persistent postural perceptual dizziness (PPPD) is the most common
      vestibular syndrome in middle-aged patients. Multisensory maladjustment involving
      alterations of sensory response pattern including vestibular, visual and motion
      stimuli is thought to be a key pathophysiological correlate of this disorder.
      OBJECTIVE: We aimed to identify regional gray matter changes in PPPD patients
      that might be involved in the underlying pathophysiology of this disorder.
      METHODS: 42 PPPD patients and healthy age and gender matched controls were
      investigated using magnetic resonance imaging-based voxel-based morphometry. All
      patients fulfilled the current diagnostic criteria for PPPD, established by the
      Barany-Society based on previous criteria for chronic subjective dizziness and
      phobic postural vertigo. RESULTS: PPPD patients showed gray matter volume
      decrease in the temporal cortex, cingulate cortex, precentral gyrus, hippocampus,
      dorsolateral prefrontal cortex, caudate nucleus and the cerebellum. A negative
      correlation of disease duration and gray matter volume was observed in the visual
      cortex, supplementary motor area and somatosensory processing structures.
      CONCLUSIONS: In patients with PPPD areas involved in multisensory vestibular
      processing show gray matter volume decrease. These brain regions resemble those
      previously described for other vestibular disorders. Longer duration of disease
      leads to a more pronounced gray matter alteration, which might represent
      maladaptive mechanisms within the course of disease.

PMID- 29167055
TI  - A Better Understanding of Brain Involvement in 22q11.2 Deletion Syndrome.

PMID- 29167056
TI  - Diffusion Tensor Imaging as a Biomarker to Differentiate Acute Disseminated
      Encephalomyelitis From Multiple Sclerosis at First Demyelination.
AB  - BACKGROUND: There are no clinical features or biomarkers that can reliably
      differentiate acute disseminated encephalomyelitis from multiple sclerosis at the
      first demyelination attack. Consequently, a final diagnosis is sometimes delayed
      by months and years of follow-up. Early treatment for multiple sclerosis is
      recommended to reduce long-term disability. Therefore, we intend to explore
      neuroimaging biomarkers that can reliably distinguish between the two diagnoses.
      METHODS: We reviewed prospectively collected clinical, standard MRI and diffusion
      tensor imaging data from 12 pediatric patients who presented with acute
      demyelination with and without encephalopathy. Patients were followed for an
      average of 6.5 years to determine the accuracy of final diagnosis. Final
      diagnosis was determined using 2013 International Pediatric MS Study Group
      criteria. Control subjects consisted of four age-matched healthy individuals for
      each patient. RESULTS: The study population consisted of six patients with
      central nervous system demyelination with encephalopathy with a presumed
      diagnosis of acute disseminated encephalomyelitis and six without encephalopathy
      with a presumed diagnosis of multiple sclerosis or clinically isolated syndrome
      at high risk for multiple sclerosis. During follow-up, two patients with initial
      diagnosis of acute disseminated encephalomyelitis were later diagnosed with
      multiple sclerosis. Diffusion tensor imaging region of interest analysis of
      baseline scans showed differences between final diagnosis of multiple sclerosis
      and acute disseminated encephalomyelitis patients, whereby low fractional
      anisotropy and high radial diffusivity occurred in multiple sclerosis patients
      compared with acute disseminated encephalomyelitis patients and the age-matched
      controls. CONCLUSIONS: Fractional anisotropy and radial diffusivity measures may
      have the potential to serve as biomarkers for distinguishing acute disseminated
      encephalomyelitis from multiple sclerosis at the onset.

PMID- 29167057
TI  - A Genetic Cause of Breathing Abnormalities and Severe Abdominal Distension.

PMID- 29167058
TI  - Neuroimaging Findings in Normocephalic Newborns With Intrauterine Zika Virus
      Exposure.
AB  - BACKGROUND: Congenital Zika infection can result in a spectrum of neurological
      abnormalities in the newborn. Newborns exposed to Zika virus in utero often have
      neuroimaging as part of their clinical evaluation. METHODS: Through the
      Congenital Zika Program at Children's National Health System in Washington DC, we
      performed fetal or neonatal neuroimaging, including magnetic resonance imaging
      and ultrasound, on over 70 fetuses or neonates with intrauterine Zika exposure.
      Novel findings on neonatal brain magnetic resonance imaging were observed in two
      instances. RESULTS: Gadolinium-contrast magnetic resonance imaging showed
      enhancement of multiple cranial nerves at three days of age on one infant.
      Another infant underwent magnetic resonance imaging at 16 days of age and was
      shown to have a chronic ischemic cerebral infarction. This infant had previously
      normal fetal magnetic resonance imaging. CONCLUSION: Cranial nerve enhancement
      and cerebral infarction may be among the expanding list of neurological findings
      in congenital Zika infection. Postnatal brain magnetic resonance imaging should
      be considered for newborns exposed to Zika virus in utero.

PMID- 29167060
TI  - Aging process, adherence to Mediterranean diet and nutritional status in a large
      cohort of nonagenarians: Effects on endothelial progenitor cells.
AB  - BACKGROUND AND AIM: Adherence to the Mediterranean Diet (MD) has been associated
      with a longer and better life. The aim of this study was to examine the effects
      of adherence to the MD, and of nutritional habits on endothelial progenitor
      (EPCs) and circulating progenitor (CPCs) cells in a cohort of nonagenarians
      enrolled within the Mugello Study, an epidemiological study aimed at
      investigating both clinically relevant geriatric items and various health issues,
      including those related to nutritional status. METHODS AND RESULTS: Four hundred
      twenty-one nonagenarians (306 F, 115 M, mean age: 93.1 +/- 3.2 years) were
      evaluated. Adherence to MD was assessed through the Mediterranean Diet Score.
      Elderly subjects who were in the fourth quartile of the Mediterranean diet score
      showed significantly higher EPCs than subjects grouped into the other three
      quartiles. After adjustment for confounders, elderly subjects who were in the
      highest quartile of adherence to the MD score reported to have EPCs' levels
      significantly higher than those who reported lower values of adherence to the MD.
      Furthermore, by analyzing different food categories, it was reported that daily
      consumption of olive oil and a higher consumption of fruit and vegetables showed
      higher CPCs CD34+ and EPCs CD34+/KDR+ than subjects with not daily or lower
      consumption. CONCLUSION: Our results support the hypothesis that the adherence to
      MD, as well as a daily consumption of olive oil and fruit and vegetables,
      characteristics of MD, may protect against the development of endothelial
      dysfunction through increasing EPCs and CPCs in older age.

PMID- 29167059
TI  - Dietary total, animal, vegetable calcium and type 2 diabetes incidence among
      Korean adults: The Korean Multi-Rural Communities Cohort (MRCohort).
AB  - BACKGROUND AND AIMS: Although a possible mechanism for developing type 2 diabetes
      in relation to calcium intake has been suggested, there is currently little
      epidemiological evidence on the association between dietary calcium and type 2
      diabetes (T2D). This study aimed to evaluate the prospective association between
      dietary calcium and T2D incidence among adults 40 years of age or over, from the
      Multi-rural Communities Cohort (MRCohort), South Korea. METHODS AND RESULTS: In
      total, 8313 participants (3033 men and 5280 women) who did not have diabetes at
      baseline were recruited between 2005 and 2013. The incidence rate ratio (IRR) was
      estimated using a modified Poisson regression model with a robust error
      estimator. During follow-up (31,570 person-years), 322 T2D cases were newly
      diagnosed. Dietary calcium (total and vegetable calcium) were inversely
      associated with the risk of T2D incidence among women (IRR = 0.61, 95% CI = 0.43
      0.86, P for trend = 0.007 in third tertile of baseline total calcium intake
      comparing to the first tertile; IRR = 0.57, 95% CI = 0.39-0.84, P for trend =
      0.006 for baseline vegetable calcium intake), not for men. The tendency of those
      inverse associations remained in both the normal fasting blood glucose group and
      the impaired fasting blood glucose group and were independent of obesity,
      smoking, and magnesium intake. CONCLUSIONS: Total and vegetable calcium may be
      inversely associated with T2D incidence among women, regardless of impaired
      fasting blood glucose group or normal group. The associations may be potentially
      dose-responsive. Moderate dietary calcium may be related to lower risk of T2D
      incidence comparing to low intake group among women.

PMID- 29167061
TI  - Implementation and outcomes of hospital-wide computerized antimicrobial approval
      system and on-the-spot education in a traumatic intensive care unit in Taiwan.
AB  - BACKGROUND/PURPOSE: Inappropriate prescribing of antibiotics is a major health
      care problem in intensive care units (ICUs). This study evaluates the impact of a
      direct hospital-wide computerized antimicrobial approval system (HCAAS) and on
      the-spot education for practitioners in a neurosurgical ICU in Taiwan. METHODS:
      We retrospectively analyzed the medical records monthly of patients who were
      admitted to the neurosurgical ICU during a period of 7 years and 7 months. A
      pretest-post-test time series analysis, comparing the three periods: period I (no
      infectious disease (ID) physician), period II (part-time ID physicians), and
      period III (full-time ID physician). Antimicrobial consumption and expenditure,
      incidence of hospital-associated infections, prevalence of healthcare-associated
      bacterial isolates, in-hospital mortality rates, and indication of antibiotics
      usage were analyzed. RESULTS: Full-time ID physician can increase the consumption
      of narrow-spectrum antimicrobials (cefazolin, and cefuroxime), and decrease the
      consumptions of broad-spectrum antimicrobials (ceftazidime, cefepime, and
      vancomycin) compared to part-time ID physicians. From period I to period III, the
      expenditure of antimicrobials, incidence of hospital-associated pneumonia, and
      the in-hospital mortality rates (crude, sepsis-related, and overall infection
      related mortality) decreased statistically. The prevalence of extended-spectrum
      beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae, and
      Carbapenems-resistant Pseudomonas aeruginosa remained at low level after HCAAS
      implementation. From 2007 to 2009, the rational antibiotics usage continued to
      increase, resulting from to more prophylaxis and appropriate microbiologic proof,
      but less empiric antimicrobial therapy. CONCLUSION: Implementation of HCAAS and
      long-term on-the-spot education by full-time ID physician can reduce
      antimicrobial consumption, cost, and improve inappropriate antibiotic usage
      whilst not compromising healthcare quality.

PMID- 29167062
TI  - Mechanistic insights into the detection of free fatty and bile acids by ileal
      glucagon-like peptide-1 secreting cells.
AB  - OBJECTIVES: The aim of this study was to investigate the electrical properties of
      ileal Glucagon-like peptide 1 (GLP-1) secreting L-cells using murine organoid
      cultures and the electrophysiological and intracellular signaling pathways
      recruited following activation of the Galphaq-coupled free fatty acid receptors
      FFA1 and Galphas-coupled bile acid receptors GPBAR1. METHODS: Experiments were
      performed using ileal organoids generated from mice transgenically expressing
      fluorescent reporters (Epac2-camps and GCaMP3) under control of the proglucagon
      promoter. Electrophysiology and single cell imaging were performed on identified
      L-cells in organoids, and GLP-1 secretion from cultured organoids was measured by
      immunoassay. RESULTS: The FFA1 ligand TAK-875 triggered L-cell electrical
      activity, increased intracellular calcium, and activated a depolarizing current
      that was blocked by the TRPC3 inhibitor Pyr3. TAK-875 triggered GLP-1 secretion
      was Pyr3 sensitive, suggesting that the TRPC3 channel links FFA1 activation to
      calcium elevation and GLP-1 release in L-cells. GPBAR1 agonist triggered PKA
      dependent L-type Ca2+ current activation and action potential firing in L-cells.
      The combination of TAK-875 and a GPBAR1 agonist triggered synergistic calcium
      elevation and GLP-1 secretory responses. CONCLUSIONS: FFA1 and GPBAR1 activation
      individually increased electrical activity in L-cells by recruiting pathways that
      include activation of TRPC3 and L-type voltage-gated Ca2+ channels. Synergy
      between the pathways activated downstream of these receptors was observed both at
      the level of Ca2+ elevation and GLP-1 secretion.

PMID- 29167063
TI  - Intramuscular administration potentiates extended dwell time of mesenchymal
      stromal cells compared to other routes.
AB  - BACKGROUND: Mesenchymal stromal cells (MSCs) offer great potential for diverse
      clinical applications. However, conventional systemic infusion of MSCs limits
      their therapeutic benefit, since intravenously (IV) infused cells become
      entrapped in the lungs where their dwell time is short. METHODS: To explore
      possible alternatives to IV infusion, we used in vivo optical imaging to track
      the bio-distribution and survival of 1 million bioluminescent MSCs administered
      IV, intraperitoneally (IP), subcutaneously (SC) and intramuscularly (IM) in
      healthy athymic mice. RESULTS: IV-infused MSCs were undetectable within days of
      administration, whereas MSCs implanted IP or SC were only detected for 3 to 4
      weeks. In contrast, MSCs sourced from human umbilical cord matrix or bone marrow
      survived more than 5 months in situ when administered IM. Long-term survival was
      optimally achieved using low passage cells delivered IM. However, MSCs could
      undergo approximately 30 doublings before their dwell time was compromised. Cryo
      preserved MSCs administered IM promptly after thaw were predominantly cleared
      after 3 days, whereas equivalent cells cultured overnight prior to implantation
      survived more than 3 months. DISCUSSION: The IM route supports prolonged cell
      survival of both neo-natal and adult-derived MSCs, although short-term MSC
      survival was comparable between all tested routes up to day 3. IM implantation
      presents a useful alternative to achieve clinical benefits from prolonged MSC
      dwell time at a homeostatic implant site and is a minimally invasive delivery
      route suitable for many applications. However, optimized thaw protocols that
      restore full biological potential of cryo-preserved MSC therapies prior to
      implantation must be developed.

PMID- 29167064
TI  - The effect of adjuvant chemotherapy on symptom burden and quality of life over
      time; a preliminary prospective observational study using individual data of
      patients aged >=70 with early stage invasive breast cancer.
AB  - OBJECTIVES: We aim to assess short and long term effects of chemotherapy on
      patient-reported quality of life (QOL) and patient versus clinician symptom
      reporting in older patients with breast cancer adjusted for tumour and aging
      parameters. MATERIAL AND METHODS: In this prospective, multicentre, non
      interventional, observational study, women aged >=70years were enrolled after
      surgery and assigned to a TC chemotherapy (docetaxel and cyclophosphamide) group
      or a control group depending on their planned adjuvant treatment. Longitudinal
      multivariate models were used to assess the statistical and minimal clinically
      important difference (MCID) in the impact of TC chemotherapy over time on QOL and
      symptom burden adjusted for baseline aging and tumour parameters. Statistical
      significance was set at 5% and MCID at 10 points. RESULTS: In total, 57 patients
      were enrolled in the chemotherapy and 52 patients in the control group. Within
      the chemotherapy group, clinical deterioration was reported at 3months for
      Fatigue (17.73), Dyspnoea (17.05), Diarrhoea (12.06) and Appetite Loss (17.05)
      scores (all p<0.001). However, the scores had returned to baseline (or even
      better for Role Functioning) at year 1. No clinical deterioration was reported in
      the control group. Symptom scores as reported by patients were significantly
      (p<0.05) higher than those reported by the clinicians, even more so for Fatigue,
      Dyspnoea, and Pain. CONCLUSION: Our results show that symptom burden and
      diminished QOL in an older breast cancer population receiving adjuvant TC
      chemotherapy are short-lived and disappear after a while with no long-term
      differences compared to a similar population not receiving chemotherapy.

PMID- 29167066
TI  - Method for quantitative detection of FAM19A4 by flow cytometry using latex beads
      as solid carrier.
AB  - FAM19A4 (family with sequence similarity 19 member A4; also TAFA4) is a classical
      secretory protein expressed mainly in the central nervous system and upregulated
      significantly in lipopolysaccharide (LPS)-stimulated monocytes and macrophages.
      It is a novel cytokine ligand of formyl peptide receptor 1 (FPR1), showing
      chemotactic activities on macrophages and promoting the phagocytosis capacity and
      the release of reactive oxygen species (ROS) by macrophages upon zymosan
      stimulation. Based on the same detection principle as enzyme-linked immunosorbent
      assay (ELISA), we developed a sandwich immunoassay for quantitative detection of
      FAM19A4 in biological fluids by flow cytometry, with latex beads as solid
      carrier. The method showed good performance in a wide range of 39-10,000 pg/mL
      and possessed excellent specificity, good precision, and favorable recovery in
      several different matrices. Native FAM19A4 secreted by phorblo 12-myristate 13
      acetate (PMA) and LPS stimulated THP-1 cells could also be detected by this
      method. This method will be much helpful to FAM19A4 studies.

PMID- 29167065
TI  - A Systematic Review of Practice Guidelines and Recommendations for
      Discontinuation of Cholinesterase Inhibitors in Dementia.
AB  - Cholinesterase inhibitors (ChEIs) are the primary pharmacological treatment for
      symptom management of Alzheimer disease (AD), but they carry known risks during
      long-term use, and do not guarantee clinical effects over time. The balance of
      risks and benefits may warrant discontinuation at different points during the
      disease course. Indeed, although there is limited scientific study of
      deprescribing ChEIs, clinicians routinely face practical decisions about whether
      to continue or stop medications. This review examined published practice
      recommendations for discontinuation of ChEIs in AD. To characterize the
      scientific basis for recommendations, we first summarized randomized controlled
      trials of ChEI discontinuation. We then identified practice guidelines by
      professional societies and in textbooks and classified them according to 1)
      whether they made a recommendation about discontinuation, 2) what the
      recommendation was, and 3) the proposed grounds for discontinuation. There was no
      consensus in guidelines and textbooks about discontinuation. Most recommended
      individualized discontinuation decisions, but there was essentially no agreement
      about what findings or situations would warrant discontinuation, or even about
      what domains to consider in this process. The only relevant domain identified by
      most guidelines and textbooks was a lack of response or a loss of effectiveness,
      both of which can be difficult to ascertain in the course of a progressive
      condition. Well-designed, long-term studies of discontinuation have not been
      conducted; such evidence is needed to provide a scientific basis for practice
      guidelines. It seems reasonable to apply an individualized approach to
      discontinuation while engaging patients and families in treatment decisions. .

PMID- 29167067
TI  - Autoclavable physically-crosslinked chitosan cryogel as a wound dressing.
AB  - Moist wounds were known to heal more rapidly than dry wounds. Hydrogel wound
      dressings were suitable for the moist wound healing because of their hyperhydrous
      structure. Chitosan was a strong candidate as a base material for hydrogel wound
      dressings because the polymer had excellent biological properties that promoted
      wound healing. We previously developed physically-crosslinked chitosan cryogels,
      which were prepared solely by freeze-thawing of a chitosan-gluconic acid
      conjugate (CG) aqueous solution, for wound treatment. The CG cryogels were
      disinfected by immersing in 70% ethanol before applying to wounds in our previous
      study. In the present study, we examined the influence of autoclave sterilization
      (121 degrees C, 20 min) on the characteristics of CG cryogel because complete
      sterilization was one of the fundamental requirements for medical devices. We
      found that optimum value of gluconic acid content of CG, defined as the number of
      the incorporated gluconic acid units per 100 glucosamine units of chitosan, was
      11 for autoclaving. An increased crosslinking level of CG cryogel on autoclaving
      enhanced resistance of the gels to enzymatic degradation. Furthermore, the
      autoclaved CG cryogels retained favorable biological properties of the pre
      autoclaved CG cryogels in that they showed the same hemostatic activity and
      efficacy in repairing full-thickness skin wounds as the pre-autoclaved CG
      cryogels. These results showed the great potential of autoclavable CG cryogels as
      a practical wound dressing.

PMID- 29167068
TI  - Three-dimensional morphology of lunate surface in hip dysplasia: Theoretical
      implications for periacetabular osteotomy.
AB  - BACKGROUND: The objective of this study was to evaluate three-dimensional
      morphology of acetabular lunate surface in patients with dysplastic hip using
      three-dimensional computed tomography (CT), and to compare the lunate surface
      morphology between the normal and dysplastic hips. METHODS: Sixty seven
      dysplastic hips in symptomatic patients and 61 normal hips in healthy volunteers
      who underwent three-dimensional CT scanning were included in this study. The size
      and shape of the lunate surface was measured with a fully automated imaging
      technique using Mimics16.0 software; lunate surface morphology was compared
      between the normal and dysplastic hips on the radial spherical coordinate system.
      RESULTS: A general trend of inferomedial rotation of the lunate surface was
      observed in dysplastic hips. Dysplastic hips showed a remarkable decrease in
      total absolute and relative size of the lunate surface as compared to that in
      normal hips. The dysplastic hips were divided into four groups: superior area
      decrease group (SD); anterosuperior area decrease group (ASD); global area
      decrease group (GD); global area increase group (GI). The arc of the global
      increase (GI) subgroup (26.86%) was increased, while that of the remaining three
      subgroups was decreased as compared to that in the normal acetabulum group.
      CONCLUSION: Three-dimensional information and fundamental morphological features
      of the lunate surface in dysplastic hips were significantly different from those
      in the normal group. These findings may aid precise computational biomechanical
      analysis, preoperative planning for periacetabular osteotomy (PAO), achievement
      of satisfactory cartilaginous congruency, and judgment of postoperative prognosis
      in addition to postoperative treatment evaluation.

PMID- 29167069
TI  - Association between brain and low back pain.
AB  - Most chronic low back pain includes elements of nociceptive pain, neuropathic
      pain, and nonorganic pain. We conducted screening for nonorganic pain with use of
      the Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP), which
      is simple and can be used for multidimensional assessment. Research on pain areas
      using functional magnetic resonance imaging (fMRI) and positron emission
      tomography has shown that the dopamine system contributes to the pathology of
      chronic low back pain. Chronic low back pain patients show decreased activation
      of the anterior cingulate cortex, prefrontal cortex, and nucleus accumbens. Given
      that both the anterior cingulate cortex and prefrontal cortex belong to the
      descending inhibitory system, and that the nucleus accumbens, which is involved
      in the dopamine system, releases MU-opioids that act to relieve pain, decreased
      activation in these three brain regions may be related to decreased function of
      the descending inhibitory system. A pathological condition that can be explained
      at the molecular biological level clearly exists between chronic low back pain
      and psychosocial factors, and investigations of a pathological condition of
      chronic low back pain including brain function are needed.

PMID- 29167070
TI  - Performance of Ultrafast DCE-MRI for Diagnosis of Prostate Cancer.
AB  - RATIONALE AND OBJECTIVES: This study aimed to test high temporal resolution
      dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for different
      zones of the prostate and evaluate its performance in the diagnosis of prostate
      cancer (PCa). Determine whether the addition of ultrafast DCE-MRI improves the
      performance of multiparametric MRI. MATERIALS AND METHODS: Patients (n = 20) with
      pathologically confirmed PCa underwent preoperative 3T MRI with T2-weighted,
      diffusion-weighted, and high temporal resolution (~2.2 seconds) DCE-MRI using
      gadoterate meglumine (Guerbet, Bloomington, IN) without an endorectal coil. DCE
      MRI data were analyzed by fitting signal intensity with an empirical mathematical
      model to obtain parameters: percent signal enhancement, enhancement rate (alpha),
      washout rate (beta), initial enhancement slope, and enhancement start time along
      with apparent diffusion coefficient (ADC) and T2 values. Regions of interests
      were placed on sites of prostatectomy verified malignancy (n = 46) and normal
      tissue (n = 71) from different zones. RESULTS: Cancer (alpha = 6.45 +/- 4.71 s-1,
      beta = 0.067 +/- 0.042 s-1, slope = 3.78 +/- 1.90 s-1) showed significantly (P
      <.05) faster signal enhancement and washout rates than normal tissue (alpha = 3.0
      +/- 2.1 s-1, beta = 0.034 +/- 0.050 s-1, slope = 1.9 +/- 1.4 s-1), but showed
      similar percentage signal enhancement and enhancement start time. Receiver
      operating characteristic analysis showed area under the curve for DCE parameters
      was comparable to ADC and T2 in the peripheral (DCE 0.67-0.82, ADC 0.80, T2 0.89)
      and transition zones (DCE 0.61-0.72, ADC 0.69, T2 0.75), but higher in the
      central zone (DCE 0.79-0.88, ADC 0.45, T2 0.45) and anterior fibromuscular stroma
      (DCE 0.86-0.89, ADC 0.35, T2 0.12). Importantly, combining DCE with ADC and T2
      increased area under the curve by ~30%, further improving the diagnostic accuracy
      of PCa detection. CONCLUSION: Quantitative parameters from empirical mathematical
      model fits to ultrafast DCE-MRI improve diagnosis of PCa. DCE-MRI with higher
      temporal resolution may capture clinically useful information for PCa diagnosis
      that would be missed by low temporal resolution DCE-MRI. This new information
      could improve the performance of multiparametric MRI in PCa detection.

PMID- 29167071
TI  - Therapeutic response analysis in dogs with naturally occurring osteoarthritis.
AB  - OBJECTIVE: Reporting the rate of positive (+) and negative (-) responders based
      on an objective outcome measure of pain-related functional disability/lameness in
      dogs with naturally occurring osteoarthritis (OA), and the relationship between
      initial lameness severity and the odds of being a (+) responder. STUDY DESIGN:
      Retrospective analysis of published peer-reviewed clinical trials in dogs with
      naturally occurring OA. ANIMALS: Dogs (n = 213) with hip and/or stifle afflicted
      joints. METHODS: A responder analysis was undertaken using a previously
      determined cut-off value of +/-2.0% of body weight using the peak of vertical
      force (PVF). Among the selected trials, PVF was acquired under similar
      conditions. Therapeutic approaches were therapeutic diets, natural health
      products and nonsteroidal anti-inflammatory drugs. RESULTS: Among dogs receiving
      a therapeutic approach as described above (n = 121), 62.8% [95% confidence
      interval, 53.9-70.9] were defined as (+) responders, whereas 11.6% [7.0-18.5]
      were (-) responders, accounting for a net (+) response rate by 51.2% [42.0-60.4].
      In dogs receiving a negative control (n = 92), the net (+) response rate was 1.1%
      [0.0-5.9]. The number needed to treat was 4, and the effect size 0.7 [0.4-1.0].
      The odds ratio of being a (+) responder under the therapeutic approaches was 2.85
      [1.57-5.17] (p < 0.001). For every less severe lameness manifested with an
      increment in PVF by 1% body weight, the chance of being a (+) responder following
      treatment decreased by 9% (odds ratio 0.91 [0.86-0.97], p = 0.006). CONCLUSION
      AND CLINICAL RELEVANCE: The rate of (+) responder optimizes decision making for
      the management of pain-related clinical signs of OA. Evidence-based medicine was
      further supported by clinical metrics based on an objective outcome measure of
      pain-related functional disability/lameness. This study also revealed that dogs
      with a mild lameness are less prone to be improved, emphasizing the need to
      carefully manage OA dogs in spite of a more subtle affliction.

PMID- 29167072
TI  - Induction of anaesthesia with remifentanil after bolus midazolam administration
      in Landrace/Large White swine.
AB  - OBJECTIVE: To investigate an alternative combination for anaesthesia induction in
      swine. STUDY DESIGN: Randomized, 'blinded' experimental study. ANIMALS: Forty
      five Landrace/Large White swine weighing 20.0+/-1.5 kg. METHODS: Pulse oximetry,
      heart rate (HR) and blood pressure were measured after premedication with
      ketamine, midazolam and atropine as well as after intubation following induction
      with a fixed dose of 0.2 mg kg-1 midazolam combined with 1, 2, 3, 4 or 5 MUg kg-1
      remifentanil (groups R1, R2, R3, R4 and R5, respectively). Intubation was
      evaluated using a numerical scoring system assessing jaw relaxation, resistance
      to the laryngoscope, vocal cord position, vocal cord movement and response to
      intubation. The time required to intubate and necessity for an additional
      midazolam dose were recorded. Baseline and post-intubation variables were
      compared with paired t tests, whereas for differences between the remifentanil
      groups the Spearman's rank correlation coefficient was estimated. Multivariate
      regression analysis was performed to disentangle the effect of remifentanil dose
      and the additional midazolam. RESULTS: Higher dose of remifentanil was associated
      with better vocal cord position (p<0.001), better response to intubation
      (p<0.001), shorter time required for intubation (p=0.030) and less frequent
      necessity for additional administration of midazolam (p=0.004). In total, 39.5%
      of the animals required additional midazolam. In groups R1, R4 and R5, there were
      decreases in HRs (p=0.009, p=0.008 and p=0.032, respectively) between baseline
      and post-intubation phase; in groups R3 and R4, there were decreases in systolic
      blood pressure (p=0.040 and p=0.019, respectively). In the multivariate analysis,
      remifentanil dose was not associated with the observed changes in haemodynamic
      variables. One animal developed apnoea and four electrocardiographic anomalies;
      all resolved without pharmaceutical interventions. CONCLUSIONS AND CLINICAL
      RELEVANCE: A combination of 0.2 mg kg-1 midazolam with 4 or 5 MUg kg-1
      remifentanil may provide an alternative method of anaesthesia induction for
      swine.

PMID- 29167073
TI  - Occlusion of blood flow in the contralateral pelvic limb during positioning for
      canine total hip replacement surgery.

PMID- 29167074
TI  - Effects of Thermomechanical Stimulation during Vaccination on Anxiety, Pain, and
      Satisfaction in Pediatric Patients: A Randomized Controlled Trial.
AB  - PURPOSE: Vaccination can be a significant source of pain for pediatric patients,
      which could result in fear of medical procedures and future reluctance to seek
      medical care. It is important for nurses to provide pain prevention during these
      procedures. This study sought to measure the impact of an intervention combining
      cold and vibration on pain scores during routine pediatric immunization. DESIGN
      AND METHODS: A prospective, open-label, randomized controlled trial to examine
      the effectiveness of the Buzzy device (thermomechanical stimulation) compared to
      no intervention (control group) in reducing child-reported pain during routine
      immunization. The Wong Baker Faces scale was used to collect child, parent, and
      observer reported anxiety and pain. Parents reported satisfaction with the
      procedure and overall office visit. RESULTS: Fifty children between the ages of 3
      and 18 were included in the present analysis. Mean child-reported pain scores
      were significantly lower in the group receiving thermomechanical stimulation
      compared to control (3.56 vs 5.92, p=0.015). Buzzy did not impact child-reported
      anxiety or how much pain the child expected. Parent-reported satisfaction did not
      vary significantly between groups, but was strongly associated with parent
      reported pain scores. CONCLUSIONS: Thermomechanical stimulation with the Buzzy
      device significantly reduced pain during pediatric immunization over a wide range
      of ages compared to control, but did not impact pre-procedure anxiety. PRACTICE
      IMPLICATIONS: The Buzzy device is an easy to implement intervention to reduce
      pediatric pain during vaccination. It may have the greatest impact in younger
      children but could be offered during all immunizations.

PMID- 29167075
TI  - Provider Beliefs Regarding Early Mobilization in the Pediatric Intensive Care
      Unit.
AB  - PURPOSE: Critically ill patients are at risk for short and long term morbidity.
      Early mobilization (EM) of critically ill adults is safe and feasible, with
      improvement in outcomes. There are limited studies evaluating EM in pediatric
      critical care patients. Provider beliefs and concerns must be evaluated prior to
      EM implementation in the pediatric intensive care unit (PICU). DESIGN AND
      METHODS: A survey was distributed to PICU providers assessing beliefs and
      concerns with regards to EM of PICU patients. RESULTS: Seventy-one providers
      responded. Most staff believed EM would be beneficial. The largest perceived
      benefits were decreased length of both stay and mechanical ventilation. The
      largest perceived concerns were risk of both endotracheal tube and central venous
      catheter dislodgement. Surveyed clinicians felt significantly more comfortable
      mobilizing the oldest as compared to the youngest patients (p<0.0001). Clinicians
      also felt significantly more comfortable mobilizing patients receiving invasive
      mechanical ventilation in the oldest as compared to the youngest patients
      (p<0.0001). CONCLUSION: There is clear benefit to the EM of adult ICU patients,
      with evidence supporting its safety and feasibility. As pediatric patients pose
      different challenges, it is imperative to understand provider concerns prior to
      the implementation of EM. Our research demonstrates similar concerns between
      adult and pediatric programs, with the addition of significant concern
      surrounding EM in very young children. PRACTICE IMPLICATIONS: Understanding
      pediatric specific concerns with regards to EM will allow for the proper
      development and implementation of pediatric EM programs, allowing us to assess
      safety, feasibility, and ultimately outcomes.

PMID- 29167076
TI  - The Convergence of Two Epidemics: Vitamin D Deficiency in Obese School-aged
      Children.
AB  - PROBLEM: Vitamin D deficiency (VDD) and obesity are two interrelated global
      epidemics that affect school-aged children. This article will review the
      relationship between VDD and obesity in school-aged children and implications it
      has for the pediatric nurse (PN). ELIGIBILITY CRITERIA: Original articles of
      studies, review articles and meta-analyses were selected from the past 5years and
      pooled for review. These included obese school-aged children who had vitamin D
      insufficiency. The latest guidelines concerning the issue were also included.
      SAMPLE: Children 6-12years of age with obesity and vitamin D insufficiency.
      RESULTS: This review strongly implies obesity in children being a strong risk
      factor for VDD. Prevention of VDD starts with lifestyle changes and adequate
      dietary intake of fortified foods and current screening recommendations for VDD
      are inconsistent. Vitamin D supplementation is recommended with inadequate intake
      or deficient serum 25-hydroxyvitamin D levels or signs of hypocalcemia.
      Supplementation doses differ based on whether VDD is being prevented or being
      treated and in obese children, the Endocrine Society recommends a dose that is
      two to three times higher than for normal weight children. Subclinical signs and
      symptoms of VDD include musculoskeletal pain, fractures, reduced bone density and
      reduced immunity. CONCLUSIONS: Whereas obesity is a strong risk factor for VDD,
      more research is needed to clarify the role of VDD as a risk factor for obesity.
      IMPLICATIONS: The PN plays an essential role in preventing, screening for,
      assessing for, treating and counseling on VDD in obese school-aged children.

PMID- 29167077
TI  - The Effects of Breastfeeding in Infants With Phenylketonuria.
AB  - PURPOSE: In the early years of phenylketonuria (PKU) treatment, mothers and
      healthcare professionals often decide to discontinue breastfeeding after the
      diagnosis of PKU in infants. It was believed to be the only effective way to
      monitor the infant's intake and allow for precise titration and measurement of
      the intake of phenylalanine (Phe). In the early 1980s, with the determination of
      low concentration of Phe in breast milk, breast milk supplemented with Phe-free
      formula has become an acceptable dietary treatment for infants with PKU. Today,
      breastfeeding is encouraged and well established in PKU patients. The aim of the
      present study is to investigate the prevalence and duration of breastfeeding, the
      effect of breastfeeding on serum Phe levels, and weight gain in infants with PKU.
      DESIGN AND METHODS: Data were collected from chart reviews. Medical records of
      142 children with PKU diagnosed via the national neonatal screening program were
      analyzed retrospectively. RESULTS: Of the 41 infants with complete medical
      records, 40 (97.6%) were breastfed following delivery whereas only one (2.4%) was
      bottle fed. After the diagnosis, breastfeeding was continued in 25 (61%) infants
      with phenylalanine-free amino acid based protein substitute. The mean duration of
      breastfeeding was 7.4+/-4.0 (1-15) months. Serum Phe concentration of breastfed
      infants (280+/-163 MUmol/L) was significantly lower than non-breastfed infants
      (490+/-199 MUmol/L) (p<0.001). Mean monthly weight gain in the first year of life
      was significantly higher in breastfed patients (493+/-159 g/month) compared to
      non-breastfed patients (399+/-116 g/month) (p=0.046). CONCLUSION: In the first
      year of life, weight gain and serum Phe levels were more favorable in breastfed
      infants with PKU compared to non-breastfed infants with PKU.

PMID- 29167078
TI  - Implementation of Pediatric Early Warning Score; Adherence to Guidelines and
      Influence of Context.
AB  - PURPOSE: To describe data of Pediatric Early Warning Score (PEWS) registrations
      and to evaluate the implementation of PEWS by examining adherence to clinical
      guidelines based on measured PEWS, and to relate findings to work context. DESIGN
      AND METHODS: PEWS, as a part of a concept called Early Detection and Treatment
      Children (EDT-C) was implemented at three wards at a Children's Hospital in
      Sweden. Data were collected from the Electronic Patient Record (EPR)
      retrospectively to assess adherence to guidelines. The Alberta Context Tool (ACT)
      was used to assess work context among healthcare professionals (n=109) before
      implementation of EDT-C. RESULTS: The majority of PEWS registrations in EPR were
      low whereas 10% were moderate to high. Adherences to ward-specific guidelines at
      admission and for saturation in respiratory distress were high whereas adherence
      to pain assessment was low. There were significant differences in documented
      recommended actions between wards. Some differences in leadership and evaluation
      between wards were identified. CONCLUSIONS: Evaluation of PEWS implementation
      indicated frequent use of the tool despite most scores being low. High scores (5
      9) occurred 28 times, which may indicate that patients with a high risk of
      clinical deterioration were identified. Documentation of the consequent
      recommended actions was however incomplete and there was a large variation in
      adherence to guidelines. Contextual factors may have an impact on adherence.
      PRACTICE IMPLICATIONS: EDT-C can lead to increased knowledge about early
      detection of deterioration, strengthen nurses as professionals, optimize
      treatment and teamwork and thereby increase patient safety for children treated
      in hospitals.

PMID- 29167079
TI  - Use of Theory to Examine Health Responsibility in Urban Adolescents.
AB  - : The study's purpose was to examine the factors that may influence health
      responsibility among adolescents. More specifically, this study examined
      relationships among health responsibility, resilience, neighborhood perception,
      social support, and health promoting behaviors in adolescents, between the ages
      of 13 and 18years old. The Health Promotion Model was used as the theoretical
      framework. This study empirically tested theoretical relationships postulated in
      the literature between health responsibility and the variables: (a) resilience
      (b) social support (c) neighborhood perception (d) social support and (e) health
      promoting behaviors. DESIGN/METHODS: A correlational study design was used. A
      convenience sample of 122 adolescents in an urban setting completed
      questionnaires assessing health responsibility, resilience, social support,
      neighborhood perception, health promoting behaviors, and a demographic
      questionnaire. Pearson correlations were used to examine relationships among
      variables. RESULTS: A statistically significant relationship was found between
      health responsibility and healthy promoting behaviors (r=0.733, p<0.001) and
      between health responsibility and neighborhood perception (r=0.163, p<0.01). No
      relationships were found between the dependent variable of health responsibility
      and the independent variables of resilience and social support in this
      population. CONCLUSIONS: Study findings help contribute to the body of knowledge
      regarding the factors that influence health responsibility among urban
      adolescents to promote adoption and maintenance of healthy behaviors among this
      population. PRACTICE IMPLICATIONS: Nurses need to educate adolescents to provide
      them with a good understanding of the consequences of health behaviors so that
      they can assess their own risk and make responsible, healthy choices.

PMID- 29167080
TI  - Psychosocial Care Models for Families of Critically Ill Children in Pediatric
      Emergency Department Settings: A Scoping Review.
AB  - PROBLEM: Critical illness in children is a significant and stressful life event
      for families. Within pediatric emergency department (ED) settings it is
      acknowledged that these crises are challenging for both the families of these
      children, and for the clinical staff treating the child. Literature recommends
      routine care should include an offer to the family to be present with their
      critically ill child, however there is a lack of clarity regarding specific
      family care models or evidence-based interventions to guide clinical practice.
      ELIGIBILITY CRITERIA: Peer reviewed articles written in English, published
      between 2006 and 2016, proposing or testing psychosocial care models in pediatric
      (or mixed) emergency settings. SAMPLE: Nine articles met inclusion criteria.
      RESULTS: Search results showed limited evidence available in the literature at
      this time. Thematic analysis of article content and proposed model showed strong
      support for the benefit of family presence, including shifting the family role
      from passive to active, needing to be inclusive of the psychological impact of
      critical health events, importance of multidisciplinary education, and the need
      for additional exploratory and empirical research to evaluate and refine proposed
      care models. CONCLUSIONS: Pediatric emergency health events are challenging for
      both families and staff, and care models provide staff with a consistent,
      evidence-informed approach to caring for families in challenging situations.
      IMPLICATIONS: There is a need to find common ground from specific discipline
      guidelines into a multidisciplinary team approach for the care of families within
      emergency care.

PMID- 29167081
TI  - Randomized Trial Evaluating the Effectiveness of a Leg Crossing and Muscle
      Tensing Technique on Decreasing Vasovagal Symptoms Among Pediatric and Young
      Adult Patients Undergoing Peripheral IV Catheter Insertion.
AB  - : Peripheral intravenous (PIV) catheter insertion is a common procedure that can
      cause vasovagal symptoms. Lower extremity muscle tensing techniques decrease
      these symptoms in adults. However, there are no studies examining this technique
      in the pediatric population. OBJECTIVE: This study aims to determine whether
      pediatric patients are able to perform the technique and to determine the effects
      of this technique on vasovagal symptoms in a pediatric population. DESIGN,
      SETTING, PARTICIPANTS: A parallel-group randomized controlled trial was conducted
      with 28 patients cared for in a pediatric surgery unit. INTERVENTION: Patients
      randomized to the experimental group performed the leg crossing and muscle
      tensing technique during PIV placement. Patients in the control group received
      standard care during PIV placement. PRIMARY OUTCOME MEASURE: The primary outcome
      measure was the frequency of experiencing at least one vasovagal sign or symptom
      which included nausea, vomiting, dizziness, pallor, sweating/diaphoresis, and
      fainting. RESULTS: Patients randomized to perform the technique were able to
      perform it without difficulty. There was a lower frequency of experiencing
      vasovagal symptoms among patients in the experimental group (15%) compared to
      patients in the control group (62.5%) (Fisher's exact test, p=0.02). The number
      of vasovagal symptoms experienced by patients in the experimental group (M=0.3)
      was significantly lower than the number of vasovagal symptoms experienced by
      patients in the control group (M=1.13), t(26)=2.302, p=0.03. CONCLUSION: A leg
      crossing technique is a low cost, low risk, and effective strategy to teach to
      pediatric patients resulting in reducing vasovagal symptoms.

PMID- 29167082
TI  - Disparities in Health Literacy and Healthcare Utilization among Adolescents and
      Young Adults with Chronic or End-stage Kidney Disease.
AB  - PURPOSE: Low health literacy adversely affects health outcomes in adults with
      chronic kidney disease. The current study examined associations between
      limited/inadequate health literacy and health services utilization among
      adolescents and young adults (AYA) with chronic or end-stage kidney disease (CKD
      or ESKD). DESIGN AND METHODS: This was a retrospective cohort study that enrolled
      patients from both the pediatric- and adult-focused nephrology clinics of a major
      university hospital. Demographic information, patients' health literacy and
      numeracy skills (Newest Vital Sign), and health services utilization (emergency
      department visits, preventable hospitalizations, total hospitalizations, and
      length of stay in the hospital) were evaluated. A negative binomial regression
      model for counts tested the association between AYA patients' literacy/numeracy
      skills and health services utilization. RESULTS: The study enrolled 142
      participants, 66 (46.5%) patients from adult nephrology and 76 (53.5%) from
      pediatric nephrology clinics, with a mean age of 20.8+/-5.60years (range 12-31).
      Half of the sample (n=72, 51%) had limited health literacy skills. Health
      literacy/numeracy level was not significantly associated with total
      hospitalizations, preventable hospitalizations, emergency department (ED) visits,
      or length of hospital stay. However, public insurance/self-pay, minority race,
      and kidney transplant/dialysis diagnoses were associated with more preventable
      hospitalizations. CONCLUSIONS: Among AYA with CKD/ESKD, there were no differences
      between the low and adequate health literacy groups on health care utilization
      outcomes when modeling clinical outcomes (total hospitalizations, preventable
      hospitalizations, ED visits, and length of hospital stay) after adjusting for
      demographics and disease type. This suggests that other factors warrant
      consideration in healthcare utilization rates.

PMID- 29167083
TI  - The Effect of Diagnostic Blood Loss on Anemia and Transfusion Among Postoperative
      Patients With Congenital Heart Disease in a Pediatric Intensive Care Unit.
AB  - PURPOSE: To evaluate whether diagnostic blood loss can lead to anemia and
      consequent blood transfusion among postoperative patients with congenital heart
      disease (CHD) in the pediatric intensive care unit (PICU). DESIGN AND METHODS:
      This prospective observational study was conducted in a university-affiliated
      tertiary hospital between January and August 2016. CHD patients aged <12years,
      undergoing cardiac surgery, with a PICU stay >48h were included (n=205).
      Multivariate logistic regression analyses were used to determine the effect of
      diagnostic blood loss on anemia and transfusion. RESULTS: The mean daily
      phlebotomy volume was 5.40+/-1.94mL/d during the PICU stay (adjusted for body
      weight, 0.63+/-0.36mL/kg/d). Daily volume/kg was associated with cyanotic CHD,
      Pediatric Risk of Mortality III score, and Pediatric Logistic Organ Dysfunction
      (PELOD)-2 score. In total, 101 (49.3%) patients presented with new or more severe
      anemia after admission to PICU, which was not associated with phlebotomy volume.
      Forty-one (20.0%) children received one or more RBC transfusions during their
      PICU stay. Multivariate analysis indicated that PELOD-2 score>5, new or more
      severe anemia, and daily volume/kg of phlebotomy >0.63mL/kg/d were significantly
      associated with transfusion after 48h of admission to PICU. CONCLUSIONS: Our
      findings indicate that diagnostic blood loss is not related to postoperative
      anemia in children with CHD; however, this factor does correlate with blood
      transfusion, since it somewhat reflects the severity of illness. PRACTICE
      IMPLICATIONS: Strategies should be applied to reduce diagnostic blood loss, as
      appropriate.

PMID- 29167084
TI  - Parent's Experiences of Their Children Suffering Febrile Seizures.
AB  - PURPOSE: To explore parents' experiences of their child suffering febrile
      seizures. DESIGN AND METHOD: Seven mothers and four fathers with experience of
      one or several febrile seizures in their children were interviewed. A qualitative
      content analysis with an inductive approach was performed. RESULT: Five themes
      emerged; emotional experiences, in terms of anxiety and fear, and need for
      control, need for support, need for acknowledgement and need for comfort.
      Professional assurance and support from healthcare staff was considered important
      to help parents handle the situation. CONCLUSION: Febrile seizure caused anxiety
      due to parents' lack of comprehension about the event and how to act during the
      seizure. PRACTICE IMPLICATIONS: The pediatric nurse plays an important role in
      gaining the trust of and supporting parents whose children have suffered febrile
      seizures. They can alleviate concerns that arise, and also generate assured and
      well informed parents, who are better prepared to deal with recurrent febrile
      seizures.

PMID- 29167085
TI  - Factors Leading to Persistent Postsurgical Pain in Adolescents Undergoing Spinal
      Fusion: An Integrative Literature Review.
AB  - PROBLEM: Adolescent idiopathic scoliosis (AIS) is the most common spinal
      deformity among children and adolescents and the most frequent reason for
      corrective spinal fusion (SF). Of the children and adolescents who undergo SF, a
      significant number will experience persistent postoperative pain (PPP). This
      integrative literature review was conducted to identify and synthesize
      perioperative factors that may contribute to risk of developing PPP. ELIGIBILITY
      CRITERIA: Articles which addressed PPP within the last 10years and primary
      research on postoperative pain outcomes in adolescents after SF were selected for
      review. SAMPLE: 15 articles which met eligibility criteria were included.
      RESULTS: Preoperative pain intensity was the most significant factor identified
      in the development of PPP and increased postoperative pain. Social function and
      psychological factors also have role in the development of PPP. There were no
      theoretical models or frameworks for evaluating PPP incidence in adolescent with
      AIS after SF. CONCLUSIONS: Perioperative factors such as, preoperative pain,
      correction magnitude, pain coping, anxiety and social functioning are vital to
      understanding a child's risk of PPP following SF. There is a need for
      theoretically-based studies to assess PPP among children and adolescents with AIS
      after SF surgery. IMPLICATIONS: The Biobehavioral Pain Network (BPN) model was
      proposed, to encompass biological, social and psychological domains which may be
      responsible for incidence of PPP in children undergoing SF. Such a model can be
      used to systematically develop and evaluate personalized postoperative pain
      management strategies for this patient population.

PMID- 29167086
TI  - Outcomes of Depression Screening Among Adolescents Accessing School-based
      Pediatric Primary Care Clinic Services.
AB  - PURPOSE: Implementation of routine Patient Health Questionnaires (PHQ-9)
      screening among adolescents aged 12-18year, accessing school-based pediatric
      primary care clinic services for identification of adolescents at potential risk
      for Major Depressive disorder (MDD). DESIGN AND METHODS: Retrospective chart
      review (N=256 cases) documented PHQ-9 depression screening outcomes among
      adolescents accessing school-based pediatric primary care clinic services for
      episodic illness and wellness visits. Data analyses included descriptive
      statistical methods. RESULTS: Chart review included 137 (53.5%) females and 119
      (46.5%) males. PHQ-9 depression screening was identified for 56.3% (n=144) of
      charts with scores >=10 for 12.5% (n=18) among those screened. Mental health
      referrals were made for 83.3% (n=15) with PHQ-9 scores >=10. Dysthymia related
      concerns were reported among 20.1% (n=29) of which 55.2% (n=16) received mental
      health referrals. Female adolescents reported more sleep problems (chi2=9.174,
      p=0.002) and tiredness (chi2=6.165, p=0.013) than males. The 15-18year age group
      (chi2=5.443, p=0.020) was more likely to experience sleep problem and low self
      esteem than 12-14year age group (chi2=5.143, p=0.023). CONCLUSION: Implementation
      of PHQ-9 depression screening protocol identified MDD among adolescent accessing
      pediatric school-based primary care clinic services facilitating referrals to
      mental health providers, potentially improving morbidity and mortality among
      adolescents. PRACTICE IMPLICATIONS: MDD is common among adolescents and
      associated with functional impairments and increased morbidity and mortality. Due
      to its high prevalence, it is imperative to improve screening and treatment
      access in this population via school-based clinics.

PMID- 29167088
TI  - Network Neuroscience Theory of Human Intelligence.
AB  - An enduring aim of research in the psychological and brain sciences is to
      understand the nature of individual differences in human intelligence, examining
      the stunning breadth and diversity of intellectual abilities and the remarkable
      neurobiological mechanisms from which they arise. This Opinion article surveys
      recent neuroscience evidence to elucidate how general intelligence, g, emerges
      from individual differences in the network architecture of the human brain. The
      reviewed findings motivate new insights about how network topology and dynamics
      account for individual differences in g, represented by the Network Neuroscience
      Theory. According to this framework, g emerges from the small-world topology of
      brain networks and the dynamic reorganization of its community structure in the
      service of system-wide flexibility and adaptation.

PMID- 29167087
TI  - Eating Behaviors, Weight Bias, and Psychological Functioning in Multi-ethnic Low
      income Adolescents.
AB  - PURPOSE: The purposes of this study were to: 1) Describe the incidence of
      disordered eating, weight bias, body dissatisfaction, and psychological distress,
      2) Examine the relationship between sociodemographic variables (gender,
      ethnicity, and income) and disordered eating, weight bias, body dissatisfaction,
      and psychological distress in a sample of low-income adolescents. DESIGN AND
      METHODS: A cross-sectional study was conducted with 105 adolescents from low
      income neighborhoods. Participants completed self-report questionnaires to assess
      eating behaviors, weight bias, body dissatisfaction, and psychological
      functioning. Height and weight were measured, and information on household income
      was collected. RESULTS: The participant's mean age was 16.31 (SD=2.8) years, 66%
      female, 47% Hispanic, and 46% African American. The mean annual income was
      $17,018 (SD=11,355). Twenty-eight percent self-reported having some form of
      disordered eating, and 15% reported an eating disorder. The group with eating
      disorder reported the highest levels of weight bias (M=93.4, SD=109.6), body
      dissatisfaction (M=94.6, SD=47.6), and psychological distress (M=1.4, SD=0.97).
      CONCLUSION: This study found a high prevalence of eating disorders with eating
      disorder participants experiencing the highest levels of weight bias and
      psychological distress. Future studies are needed to identify and evaluate
      community and school-based interventions to minimize weight bias and disordered
      eating. PRACTICE IMPLICATIONS: Nurses are at the forefront of healthcare and
      should collaborate with educators, school counselors, administrators, coaches,
      parents, and students, to address weight bias and disordered eating in schools by
      implementing school-based curriculum and policies.

PMID- 29167089
TI  - Predicting Unplanned Transfers to the Intensive Care Unit: A Machine Learning
      Approach Leveraging Diverse Clinical Elements.
AB  - BACKGROUND: Early warning scores aid in the detection of pediatric clinical
      deteriorations but include limited data inputs, rarely include data trends over
      time, and have limited validation. OBJECTIVE: Machine learning methods that make
      use of large numbers of predictor variables are now commonplace. This work
      examines how different types of predictor variables derived from the electronic
      health record affect the performance of predicting unplanned transfers to the
      intensive care unit (ICU) at three large children's hospitals. METHODS: We
      trained separate models with data from three different institutions from 2011
      through 2013 and evaluated models with 2014 data. Cases consisted of patients who
      transferred from the floor to the ICU and met one or more of 5 different priori
      defined criteria for suspected unplanned transfers. Controls were patients who
      were never transferred to the ICU. Predictor variables for the models were
      derived from vitals, labs, acuity scores, and nursing assessments. Classification
      models consisted of L1 and L2 regularized logistic regression and neural network
      models. We evaluated model performance over prediction horizons ranging from 1 to
      16 hours. RESULTS: Across the three institutions, the c-statistic values for our
      best models were 0.892 (95% CI 0.875-0.904), 0.902 (95% CI 0.880-0.923), and
      0.899 (95% CI 0.879-0.919) for the task of identifying unplanned ICU transfer 6
      hours before its occurrence and achieved 0.871 (95% CI 0.855-0.888), 0.872 (95%
      CI 0.850-0.895), and 0.850 (95% CI 0.825-0.875) for a prediction horizon of 16
      hours. For our first model at 80% sensitivity, this resulted in a specificity of
      80.5% (95% CI 77.4-83.7) and a positive predictive value of 5.2% (95% CI 4.5
      6.2). CONCLUSIONS: Feature-rich models with many predictor variables allow for
      patient deterioration to be predicted accurately, even up to 16 hours in advance.

PMID- 29167090
TI  - Attrition from Web-Based Cognitive Testing: A Repeated Measures Comparison of
      Gamification Techniques.
AB  - BACKGROUND: The prospect of assessing cognition longitudinally and remotely is
      attractive to researchers, health practitioners, and pharmaceutical companies
      alike. However, such repeated testing regimes place a considerable burden on
      participants, and with cognitive tasks typically being regarded as effortful and
      unengaging, these studies may experience high levels of participant attrition.
      One potential solution is to gamify these tasks to make them more engaging:
      increasing participant willingness to take part and reducing attrition. However,
      such an approach must balance task validity with the introduction of entertaining
      gamelike elements. OBJECTIVE: This study aims to investigate the effects of
      gamelike features on participant attrition using a between-subjects, longitudinal
      Web-based testing study. METHODS: We used three variants of a common cognitive
      task, the Stop Signal Task (SST), with a single gamelike feature in each: one
      variant where points were rewarded for performing optimally; another where the
      task was given a graphical theme; and a third variant, which was a standard SST
      and served as a control condition. Participants completed four compulsory test
      sessions over 4 consecutive days before entering a 6-day voluntary testing period
      where they faced a daily decision to either drop out or continue taking part.
      Participants were paid for each session they completed. RESULTS: A total of 482
      participants signed up to take part in the study, with 265 completing the
      requisite four consecutive test sessions. No evidence of an effect of
      gamification on attrition was observed. A log-rank test showed no evidence of a
      difference in dropout rates between task variants (chi22=3.0, P=.22), and a one
      way analysis of variance of the mean number of sessions completed per participant
      in each variant also showed no evidence of a difference (F2,262=1.534, P=.21,
      partial eta2=0.012). CONCLUSIONS: Our findings raise doubts about the ability of
      gamification to reduce attrition from longitudinal cognitive testing studies.

PMID- 29167091
TI  - The Effect of Aging on Physical Performance Among Elderly Manual Workers:
      Protocol of a Cross-Sectional Study.
AB  - BACKGROUND: In 2012, the Danish Parliament decided to increase retirement age.
      Unfortunately, elderly people working in a physically demanding environment may
      be rendered unable to retain the ability to adequately perform the physical
      requirements of their jobs, due to age-related decreases in physical performance.
      Therefore, increasing the retirement age may not necessarily lead to the goal of
      keeping everybody in the labor market for a longer time. To date, our knowledge
      about the variations in physical performance of the elderly workforce is limited.
      OBJECTIVE: In this cross-sectional study we seek to investigate the effects of
      aging on physical performance among elderly manual workers. METHODS:
      Approximately 100 Danish manual workers between 50 and 70 years of age will be
      recruited. The main measurement outcomes include: (1) inflammatory status from
      blood samples; (2) body composition; (3) lung function; (4) static and dynamic
      balance; (5) reaction time, precision, and movement variability during a
      hammering task; (6) handgrip strength, rate of force development, and force
      tracking; (7) estimated maximal rate of oxygen consumption; and (8) back
      mobility. Additionally, information regarding working conditions, physical
      activity levels, and health status will be assessed with a questionnaire.
      RESULTS: Data collection is expected to take place between autumn 2017 and spring
      2018. CONCLUSIONS: This study will increase the knowledge regarding variations in
      physical performance in the elderly workforce and may identify potential
      workplace hazards. Moreover, this study might shed light on the potentially
      problematic decision to increase retirement age for all Danish citizens.

PMID- 29167093
TI  - Challenging assumptions in obesity research.

PMID- 29167094
TI  - Colleagues are best source of support for doctors facing complaints, researchers
      find.

PMID- 29167095
TI  - Accelerated access to new drugs and technologies.

PMID- 29167092
TI  - Dry Needling for Patients With Neck Pain: Protocol of a Randomized Clinical
      Trial.
AB  - BACKGROUND: Neck pain is a costly and common problem. Current treatments are not
      adequately effective for a large proportion of patients who continue to
      experience recurrent pain. Therefore, new treatment strategies should be
      investigated in an attempt to reduce the disability and high costs associated
      with neck pain. Dry needling is a technique in which a fine needle is used to
      penetrate the skin, subcutaneous tissues, and muscle with the intent to
      mechanically disrupt tissue without the use of an anesthetic. Dry needling is
      emerging as a treatment modality that is widely used clinically to address a
      variety of musculoskeletal conditions. Recent studies of dry needling in
      mechanical neck pain suggest potential benefits, but do not utilize methods
      typical to clinical practice and lack long-term follow-up. Therefore, a clinical
      trial with realistic treatment time frames and methods consistent with clinical
      practice is needed to examine the effectiveness of dry needling on reducing pain
      and enhancing function in patients presenting to physical therapy with mechanical
      neck pain. OBJECTIVE: The aim of this trial will be to examine the short- and
      long-term effectiveness of dry needling delivered by a physical therapist on
      pain, disability, and patient-perceived improvements in patients with mechanical
      neck pain. METHODS: We will conduct a randomized, double-blind, placebo
      controlled trial in accordance with the CONSORT guidelines. A total of 76
      patients over the age of 18 with acute or chronic mechanical neck pain resulting
      from postural dysfunction, trauma, or insidious onset who are referred to
      physical therapy will be enrolled after meeting the eligibility criteria.
      Subjects will be excluded if they have previous history of surgery, whiplash in
      the last 6 weeks, nerve root compression, red flags, or contraindications to dry
      needling or manual therapy. Participants will be randomized to receive (1) dry
      needling, manual therapy, and exercise or (2) sham dry needling, manual therapy,
      and exercise. Participants will receive seven physical therapy treatments lasting
      45 minutes each over a maximum of 4 weeks. The primary outcome will be disability
      as measured by the Neck Disability Index. Secondary outcomes include the
      following: pain, patient-perceived improvement, patient expectations, and
      successful blinding to the needling intervention. Outcome measures will be
      assessed at 4 weeks, 6 months, and 12 months by an assessor who is blind to the
      group allocation of the participants to determine the short- and long-term
      treatment effects. We will examine the primary aim with a two-way, repeated
      measures analysis of variance with treatment group as the between-subjects
      variable and time as the within-subjects variable. The hypothesis of interest
      will be the two-way group by time interaction. An a priori alpha level of .05
      will be used for all analyses. RESULTS: Recruitment is currently underway and is
      expected to be completed by the end of 2017. Data collection for long-term
      outcomes will occur throughout 2017 and 2018. Data analysis, preparation, and
      publication submission is expected to occur throughout the final three quarters
      of 2018. CONCLUSIONS: The successful completion of this trial will provide
      evidence to demonstrate whether dry needling is effective for the management of
      mechanical neck pain when used in a combined treatment approach, as is the common
      clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT02731014;
      https://clinicaltrials.gov/ct2/show/NCT02731014 (Archived by WebCite at
      http://www.webcitation.org/6ujZgbhsq).

PMID- 29167096
TI  - Jeremy Hunt must consult properly on accountable care organisations.

PMID- 29167097
TI  - Amsterdam to host EMA after Brexit triggers withdrawal from London.

PMID- 29167098
TI  - Private insurance clubs for surgeons.

PMID- 29167099
TI  - Chancellor's L2.8bn NHS cash pledge will not ease pressures, leaders warn.

PMID- 29167100
TI  - Difficult behaviour can protect patients.

PMID- 29167101
TI  - Children need single point of access to talking therapies, says children's
      commissioner.

PMID- 29167103
TI  - Adam Kay: Mirth partner.

PMID- 29167104
TI  - Scientists wake up to coffee's benefits.

PMID- 29167105
TI  - Criteria for allocating new medical school places are too broad, expert warns.

PMID- 29167102
TI  - Coffee consumption and health: umbrella review of meta-analyses of multiple
      health outcomes.
AB  - Objectives To evaluate the existing evidence for associations between coffee
      consumption and multiple health outcomes.Design Umbrella review of the evidence
      across meta-analyses of observational and interventional studies of coffee
      consumption and any health outcome.Data sources PubMed, Embase, CINAHL, Cochrane
      Database of Systematic Reviews, and screening of references.Eligibility criteria
      for selecting studies Meta-analyses of both observational and interventional
      studies that examined the associations between coffee consumption and any health
      outcome in any adult population in all countries and all settings. Studies of
      genetic polymorphisms for coffee metabolism were excluded.Results The umbrella
      review identified 201 meta-analyses of observational research with 67 unique
      health outcomes and 17 meta-analyses of interventional research with nine unique
      outcomes. Coffee consumption was more often associated with benefit than harm for
      a range of health outcomes across exposures including high versus low, any versus
      none, and one extra cup a day. There was evidence of a non-linear association
      between consumption and some outcomes, with summary estimates indicating largest
      relative risk reduction at intakes of three to four cups a day versus none,
      including all cause mortality (relative risk 0.83 (95% confidence interval 0.79
      to 0.88), cardiovascular mortality (0.81, 0.72 to 0.90), and cardiovascular
      disease (0.85, 0.80 to 0.90). High versus low consumption was associated with an
      18% lower risk of incident cancer (0.82, 0.74 to 0.89). Consumption was also
      associated with a lower risk of several specific cancers and neurological,
      metabolic, and liver conditions. Harmful associations were largely nullified by
      adequate adjustment for smoking, except in pregnancy, where high versus low/no
      consumption was associated with low birth weight (odds ratio 1.31, 95% confidence
      interval 1.03 to 1.67), preterm birth in the first (1.22, 1.00 to 1.49) and
      second (1.12, 1.02 to 1.22) trimester, and pregnancy loss (1.46, 1.06 to 1.99).
      There was also an association between coffee drinking and risk of fracture in
      women but not in men.Conclusion Coffee consumption seems generally safe within
      usual levels of intake, with summary estimates indicating largest risk reduction
      for various health outcomes at three to four cups a day, and more likely to
      benefit health than harm. Robust randomised controlled trials are needed to
      understand whether the observed associations are causal. Importantly, outside of
      pregnancy, existing evidence suggests that coffee could be tested as an
      intervention without significant risk of causing harm. Women at increased risk of
      fracture should possibly be excluded.

PMID- 29167110
TI  - Blocking IDO1 Helps Shrink Bladder, Cervical Tumors.
AB  - Findings from a phase I/IIa study indicate that combining the investigational
      indoleamine 2,3-dioxygenase 1 inhibitor BMS-986205 with nivolumab is safe and
      boosts response rates among patients with bladder and cervical cancers.

PMID- 29167111
TI  - HLA Loss Facilitates Immune Escape.
AB  - Researchers have developed a new software tool, called LOHHLA, which can pinpoint
      allele-specific HLA loss in tumors. When applied to a cohort of patients with non
      small cell lung cancer, this genomic event was detected in 40% of cases,
      increasing in frequency as the disease spread to the brain.

PMID- 29167106
TI  - Use of a primary care online consultation system, by whom, when and why:
      evaluation of a pilot observational study in 36 general practices in South West
      England.
AB  - OBJECTIVES: Evaluation of a pilot study of an online consultation system in
      primary care. We describe who used the system, when and why, and the National
      Health Service costs associated with its use. DESIGN: 15-month observational
      study. SETTING: Primary care practices in South West England. RESULTS: 36 General
      practices covering 396 828 patients took part in the pilot. The online
      consultation website was viewed 35 981 times over the pilot period (mean 9.11
      visits per 1000 patients per month). 7472 patients went on to complete an 'e
      consultation' (mean 2.00 online consultations per 1000 patients per month). E
      consultations were mainly performed on weekdays and during normal working hours.
      Patient records (n=485) were abstracted for eight practices and showed that women
      were more likely to use e-consultations than men (64.7% vs 35.3%) and users had a
      median age of 39 years (IQR 30-50). The most common reason for an e-consultation
      was an administrative request (eg, test results, letters and repeat prescriptions
      (22.5%)) followed by infections/immunological issues (14.4%). The majority of
      patients (65.2%) received a response within 2 days. The most common outcome was a
      face-to-face (38%) or telephone consultation (32%). The former were more often
      needed for patients consulting about new conditions (OR 1.56, 95% CI 1.05 to
      2.27, p=0.049). The average cost of a practice's response to an e-consultation
      was L36.28, primarily triage time and resulting face-to-face/telephone
      consultations needed. CONCLUSIONS: Use of e-consultations is very low,
      particularly at weekends. Unless this can be improved, any impact on staff
      workload and patient waiting times is likely to be negligible. It is possible
      that use of e-consultations increases primary care workload and costs. Online
      consultation systems could be developed to improve efficiency both for staff and
      patients. These findings have implications for software developers as well as
      primary care services and policy-makers who are considering investing in online
      consultation systems.

PMID- 29167112
TI  - All stakeholders must commit to improving research integrity, medical editors
      tell MPs.

PMID- 29167114
TI  - Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional
      needs under protein restriction.
AB  - Glutamine (Gln) is the most concentrated amino acid in blood and considered
      conditionally essential. Its requirement is increased during physiological
      stress, such as malnutrition or illness, despite its production by muscle and
      other organs. In the malnourished state, Gln has been suggested to have a trophic
      effect on the exocrine pancreas and small intestine. However, the Gln transport
      capacity, the functional relationship of these two organs, and the potential role
      of the Gln-glutamate (Glu) cycle are unknown. We observed that pancreatic acinar
      cells express lower levels of Glu than Gln transporters. Consistent with this
      expression pattern, the rate of Glu influx into acinar cells was approximately
      sixfold lower than that of Gln. During protein restriction, acinar cell
      glutaminase expression was increased and Gln accumulation was maintained.
      Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the
      lumen of the small intestine was maintained. In the intestinal lumen, Glu
      absorption was preserved and Glu dehydrogenase expression was augmented,
      potentially providing the substrates for increasing energy production via the TCA
      cycle. Our findings suggest that one mechanism by which Gln exerts a positive
      effect on exocrine pancreas and small intestine involves the Gln metabolism in
      acinar cells and the secretion of Glu into the small intestine lumen. The
      exocrine pancreas acinar cells not only avidly accumulate Gln but metabolize Gln
      to generate energy and to synthesize Glu for secretion in the pancreatic juice.
      Secreted Glu is suggested to play an important role during malnourishment in
      sustaining small intestinal homeostasis. NEW & NOTEWORTHY Glutamine (Gln) has
      been suggested to have a trophic effect on exocrine pancreas and small intestine
      in malnourished states, but the mechanism is unknown. In this study, we suggest
      that this trophic effect derives from an interorgan relationship between exocrine
      pancreas and small intestine for Gln-glutamate (Glu) utilization involving the
      uptake and metabolism of Gln in acinar cells and secretion of Glu into the lumen
      of the small intestine.

PMID- 29167113
TI  - Irritable bowel syndrome patients have SCN5A channelopathies that lead to
      decreased NaV1.5 current and mechanosensitivity.
AB  - The SCN5A-encoded voltage-gated mechanosensitive Na+ channel NaV1.5 is expressed
      in human gastrointestinal smooth muscle cells and interstitial cells of Cajal.
      NaV1.5 contributes to smooth muscle electrical slow waves and mechanical
      sensitivity. In predominantly Caucasian irritable bowel syndrome (IBS) patient
      cohorts, 2-3% of patients have SCN5A missense mutations that alter NaV1.5
      function and may contribute to IBS pathophysiology. In this study we examined a
      racially and ethnically diverse cohort of IBS patients for SCN5A missense
      mutations, compared them with IBS-negative controls, and determined the resulting
      NaV1.5 voltage-dependent and mechanosensitive properties. All SCN5A exons were
      sequenced from somatic DNA of 252 Rome III IBS patients with diverse ethnic and
      racial backgrounds. Missense mutations were introduced into wild-type SCN5A by
      site-directed mutagenesis and cotransfected with green fluorescent protein into
      HEK-293 cells. NaV1.5 voltage-dependent and mechanosensitive functions were
      studied by whole cell electrophysiology with and without shear force. Five of 252
      (2.0%) IBS patients had six rare SCN5A mutations that were absent in 377 IBS
      negative controls. Six of six (100%) IBS-associated NaV1.5 mutations had voltage
      dependent gating abnormalities [current density reduction (R225W, R433C, R986Q,
      and F1293S) and altered voltage dependence (R225W, R433C, R986Q, G1037V, and
      F1293S)], and at least one kinetic parameter was altered in all mutations. Four
      of six (67%) IBS-associated SCN5A mutations (R225W, R433C, R986Q, and F1293S)
      resulted in altered NaV1.5 mechanosensitivity. In this racially and ethnically
      diverse cohort of IBS patients, we show that 2% of IBS patients harbor SCN5A
      mutations that are absent in IBS-negative controls and result in NaV1.5 channels
      with abnormal voltage-dependent and mechanosensitive function. NEW & NOTEWORTHY
      The voltage-gated Na+ channel NaV1.5 contributes to smooth muscle physiology and
      electrical slow waves. In a racially and ethnically mixed irritable bowel
      syndrome cohort, 2% had mutations in the NaV1.5 gene SCN5A. These mutations were
      absent in irritable bowel syndrome-negative controls. Most mutant NaV1.5 channels
      were loss of function in voltage dependence or mechanosensitivity.

PMID- 29167115
TI  - Epigenetic modulation of intestinal Na+/H+ exchanger-3 expression.
AB  - Na+/H+ exchanger-3 (NHE3) is crucial for intestinal Na+ absorption, and its
      reduction has been implicated in infectious and inflammatory bowel diseases (IBD)
      associated diarrhea. Epigenetic mechanisms such as DNA methylation are involved
      in the pathophysiology of IBD. Whether changes in DNA methylation are involved in
      modulating intestinal NHE3 gene expression is not known. Caco-2 and HuTu 80 cells
      were used as models of human intestinal epithelial cells. Normal C57/BL6, wild
      type, or growth arrest and DNA damage-inducible 45b (GADD45b) knockout (KO) mice
      were used as in vivo models. NHE3 gene DNA methylation levels were assessed by
      MBDCap (MethyMiner) assays. Results demonstrated that in vitro methylation of
      NHE3 promoter construct (p-1509/+127) cloned into a cytosine guanine dinucleotide
      free lucia vector decreased the promoter activity in Caco-2 cells. DNA
      methyltransferase inhibitor 5-azacytidine (10 MUM, 24 h) caused a significant
      decrease in DNA methylation of the NHE3 gene and concomitantly increased NHE3
      expression in Caco-2 cells. Similarly, 5-azacytidine treatment increased NHE3
      mRNA levels in HuTu 80 cells. 5-Azacytidine treatment for 3 wk (10 mg/kg body wt
      ip, 3 times/wk) also resulted in an increase in NHE3 expression in the mouse
      ileum and colon. Small-interfering RNA knockdown of GADD45b (protein involved in
      DNA demethylation) in Caco-2 cells decreased NHE3 mRNA expression. Furthermore,
      there was a significant decrease in NHE3 mRNA and protein expression in the ileum
      and colon of GADD45b KO mice. Our findings demonstrate that NHE3 gene expression
      is regulated by changes in its DNA methylation. NEW & NOTEWORTHY Our studies for
      the first time demonstrate that Na+/H+ exchanger-3 gene expression is regulated
      by an epigenetic mechanism involving DNA methylation.

PMID- 29167116
TI  - Medullary raphe nuclei activate the lumbosacral defecation center through the
      descending serotonergic pathway to regulate colorectal motility in rats.
AB  - Colorectal motility is regulated by two defecation centers located in the brain
      and spinal cord. In previous studies, we have shown that administration of
      serotonin (5-HT) in the lumbosacral spinal cord causes enhancement of colorectal
      motility. Because spinal 5-HT is derived from neurons of the medullary raphe
      nuclei, including the raphe magnus, raphe obscurus, and raphe pallidus, we
      examined whether stimulation of the medullary raphe nuclei enhances colorectal
      motility via the lumbosacral defecation center. Colorectal pressure was recorded
      with a balloon in vivo in anesthetized rats. Electrical stimulation of the
      medullary raphe nuclei failed to enhance colorectal motility. Because GABAergic
      neurons can be simultaneously activated by the raphe stimulation and released
      GABA masks accelerating actions of the raphe nuclei on the lumbosacral defecation
      center, a GABAA receptor antagonist was preinjected intrathecally to manifest
      excitatory responses. When spinal GABAA receptors were blocked by the antagonist,
      electrical stimulation of the medullary raphe nuclei increased colorectal
      contractions. This effect of the raphe nuclei was inhibited by intrathecal
      injection of 5-hydroxytryptamine type 2 (5-HT2) and type 3 (5-HT3) receptor
      antagonists. In addition, injection of a selective 5-HT reuptake inhibitor in the
      lumbosacral spinal cord augmented the raphe stimulation-induced enhancement of
      colorectal motility. Transection of the pelvic nerves, but not transection of the
      colonic nerves, prevented the effect of the raphe nuclei on colorectal motility.
      These results demonstrate that activation of the medullary raphe nuclei causes
      augmented contractions of the colorectum via 5-HT2 and 5-HT3 receptors in the
      lumbosacral defecation center. NEW & NOTEWORTHY We have shown that electrical
      stimulation of the medullary raphe nuclei causes augmented contractions of the
      colorectum via pelvic nerves in rats. The effect of the medullary raphe nuclei on
      colorectal motility is exerted through activation of 5-hydroxytryptamine type 2
      and type 3 receptors in the lumbosacral defecation center. The descending
      serotoninergic raphespinal tract represents new potential therapeutic targets
      against colorectal dysmotility such as irritable bowel syndrome.

PMID- 29167117
TI  - Effect of 6 wk of high-intensity one-legged cycling on functional sympatholysis
      and ATP signaling in patients with heart failure.
AB  - Breathlessness during daily activities is the primary symptom in patients with
      heart failure (HF). Poor correlation between the hemodynamic parameters of left
      ventricular performance and perceived symptoms suggests that other factors, such
      as skeletal muscle function, play a role in determining exercise capacity. We
      investigated the effect of 6 wk of high-intensity, one-legged cycling (HIC; 8 * 4
      at 90% one-legged cycling max) on 1) the ability to override sympathetic
      vasoconstriction (arterial infusion of tyramine) during one-legged knee-extensor
      exercise (KEE), 2) vascular function (arterial infusion of ACh, sodium
      nitroprusside, tyramine, and ATP), and 3) exercise capacity in HF patients with
      reduced ejection fraction ( n = 8) compared with healthy individuals ( n = 6).
      Arterial tyramine infusion lowered leg blood flow and leg vascular conductance at
      rest and during KEE before the training intervention in both groups ( P < 0.05)
      but not during KEE after the training intervention. There was no difference
      between groups. The peak vasodilatory response to ATP was blunted in HF patients
      ( P < 0.05), whereas there was no difference in ACh- and sodium nitroprusside
      induced vasodilation between HF patients and healthy individuals. ACh-induced
      vasodilation increased in HF patients after the training intervention ( P <
      0.05). HIC improved aerobic capacity in both groups ( P < 0.05), whereas only HF
      patients made improvements in the 6-min walking distance ( P < 0.05). These
      results suggest that exercise hyperemia and functional sympatholysis are not
      altered in HF patients and that functional sympatholysis is improved with HIC in
      both HF patients and healthy individuals. Moreover, these results suggest that
      the peak vasodilatory response to ATP is blunted in HF. NEW & NOTEWORTHY The
      ability to override sympathetic vasoconstrictor activity (by arterial tyramine
      infusion) during exercise is not different between heart failure patients and
      healthy individuals and is improved by high-intensity, one-legged cycling
      training. The peak vasodilatory response to ATP is reduced in heart failure
      patients.

PMID- 29167118
TI  - Exercise facilitates early recognition of cardiac and vascular remodeling in
      chronic thromboembolic pulmonary hypertension in swine.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 4% of patients
      after pulmonary embolism and is accompanied by an impaired exercise tolerance,
      which is ascribed to the increased right ventricular (RV) afterload in
      combination with a ventilation/perfusion (V/Q) mismatch in the lungs. The present
      study aimed to investigate changes in arterial Po2 and hemodynamics in response
      to graded treadmill exercise during development and progression of CTEPH in a
      novel swine model. Swine were chronically instrumented and received multiple
      pulmonary embolisms by 1) microsphere infusion (Spheres) over 5 wk, 2)
      endothelial dysfunction by administration of the endothelial nitric oxide
      synthase inhibitor Nomega-nitro-l-arginine methyl ester (L-NAME) for 7 wk, 3)
      combined pulmonary embolisms and endothelial dysfunction (L-NAME + Spheres), or
      4) served as sham-operated controls (sham). After a 9 wk followup, embolization
      combined with endothelial dysfunction resulted in CTEPH, as evidenced by mean
      pulmonary artery pressures of 39.5 +/- 5.1 vs. 19.1 +/- 1.5 mmHg (Spheres, P <
      0.001), 22.7 +/- 2.0 mmHg (L-NAME, P < 0.001), and 20.1 +/- 1.5 mmHg (sham, P <
      0.001), and a decrease in arterial Po2 that was exacerbated during exercise,
      indicating V/Q mismatch. RV dysfunction was present after 5 wk of embolization,
      both at rest (trend toward increased RV end-systolic lumen area, P = 0.085, and
      decreased stroke volume index, P = 0.042) and during exercise (decreased stroke
      volume index vs. control, P = 0.040). With sustained pulmonary hypertension, RV
      hypertrophy (Fulton index P = 0.022) improved RV function at rest and during
      exercise, but this improvement was insufficient in CTEPH swine to result in an
      exercise-induced increase in cardiac index. In conclusion, embolization in
      combination with endothelial dysfunction results in CTEPH in swine. Exercise
      increased RV afterload, exacerbated the V/Q mismatch, and unmasked RV
      dysfunction. NEW & NOTEWORTHY Here, we present the first double-hit chronic
      thromboembolic pulmonary hypertension swine model. We show that embolization as
      well as endothelial dysfunction is required to induce sustained pulmonary
      hypertension, which is accompanied by altered exercise hemodynamics and an
      exacerbated ventilation/perfusion mismatch during exercise.

PMID- 29167119
TI  - Revisiting the physiological effects of exercise training on autonomic regulation
      and chemoreflex control in heart failure: does ejection fraction matter?
AB  - Heart failure (HF) is a global public health problem that, independent of its
      etiology [reduced (HFrEF) or preserved ejection fraction (HFpEF)], is
      characterized by functional impairments of cardiac function, chemoreflex
      hypersensitivity, baroreflex sensitivity (BRS) impairment, and abnormal autonomic
      regulation, all of which contribute to increased morbidity and mortality.
      Exercise training (ExT) has been identified as a nonpharmacological therapy
      capable of restoring normal autonomic function and improving survival in patients
      with HFrEF. Improvements in autonomic function after ExT are correlated with
      restoration of normal peripheral chemoreflex sensitivity and BRS in HFrEF. To
      date, few studies have addressed the effects of ExT on chemoreflex control, BRS,
      and cardiac autonomic control in HFpEF; however, there are some studies that have
      suggested that ExT has a beneficial effect on cardiac autonomic control. The
      beneficial effects of ExT on cardiac function and autonomic control in HF may
      have important implications for functional capacity in addition to their obvious
      importance to survival. Recent studies have suggested that the peripheral
      chemoreflex may also play an important role in attenuating exercise intolerance
      in HFrEF patients. The role of the central/peripheral chemoreflex, if any, in
      mediating exercise intolerance in HFpEF has not been investigated. The present
      review focuses on recent studies that address primary pathophysiological
      mechanisms of HF (HFrEF and HFpEF) and the potential avenues by which ExT exerts
      its beneficial effects.

PMID- 29167120
TI  - Acute lysyl oxidase inhibition alters microvascular function in normotensive but
      not hypertensive men and women.
AB  - The lysyl oxidase (LOX) family of enzymes regulates collagen cross-linking. LOX
      is upregulated in hypertension, increasing vascular stiffness. In vivo human
      research is sparse, as long-term LOX inhibition in animals causes vascular
      instability. Our aim was to evaluate the effects of LOX inhibition on cutaneous
      microvascular function to determine whether LOX function was upregulated in
      hypertensive humans. Four intradermal microdialysis fibers were placed in the
      forearm of 10 young [age: 24 +/- 1 yr, mean arterial pressure (MAP): 87 +/- 2
      mmHg], 10 normotensive (age: 50 +/- 2 yr, MAP: 84 +/- 1 mmHg), and 10
      hypertensive (age: 53 +/- 2 yr, MAP: 112 +/- 2 mmHg) subjects. Two sites were
      perfused with 10 mM beta-aminopropionitrile (BAPN) to inhibit LOX. The remaining
      two sites were perfused with lactated Ringer solution (control). A norepinephrine
      dose response (10-12-10-2 M) was performed to examine receptor-mediated
      vasoconstrictor function. A sodium nitroprusside dose response (10-8-10-1.3 M)
      was performed to examine vascular smooth muscle vasodilator function. Red blood
      cell flux was measured via laser-Doppler flowmetry and normalized to cutaneous
      vascular conductance (flux/MAP). LogEC50 values were calculated to determine
      changes in vasosensitivity. Skin tissue samples were analyzed for both
      extracellular matrix-bound and soluble LOX. LOX inhibition augmented
      vasoconstrictor sensitivity in young (control: -6.0 and BAPN: -7.1, P = 0.03) and
      normotensive (control: -4.8 and BAPN: -7.0, P = 0.01) but not hypertensive
      (control: -6.0 and BAPN: -6.1, P = 0.79) men and women. Relative to young
      subjects, extracellular matrix-bound LOX expression was higher in hypertensive
      subjects (young: 100 +/- 8 and hypertensive: 162 +/- 8, P = 0.002). These results
      suggest that upregulated LOX may contribute to the vascular stiffness and
      microvascular dysfunction characteristic in hypertension. NEW & NOTEWORTHY Matrix
      bound lysyl oxidase (LOX) and LOX-like 2 expression are upregulated in the
      microvasculature of hypertensive men and women. Microvascular responsiveness to
      exogenous stimuli is altered with localized LOX inhibition in healthy men and
      women but not hypertensive adults. The LOX family differentially affects
      microvascular function in hypertensive and normotensive men and women.

PMID- 29167121
TI  - Flow-mediated dilation stimulated by sustained increases in shear stress: a
      useful tool for assessing endothelial function in humans?
AB  - Investigations of human conduit artery endothelial function via flow-mediated
      vasodilation (FMD) have largely been restricted to the reactive hyperemia (RH)
      technique, wherein a transient increase in shear stress after the release of limb
      occlusion stimulates upstream conduit artery vasodilation (RH-FMD). FMD can also
      be assessed in response to sustained increases in shear stress [sustained
      stimulus (SS)-FMD], most often created with limb heating or exercise. Exercise in
      particular creates a physiologically relevant stimulus because shear stress
      increases, and FMD occurs, during typical day-to-day activity. Several studies
      have identified that various conditions and acute interventions have a disparate
      impact on RH-FMD versus SS-FMD, sometimes with only the latter demonstrating
      impairment. Indeed, evidence suggests that transient (RH) and sustained (SS)
      shear stress stimuli may be transduced via different signaling pathways, and, as
      such, SS-FMD and RH-FMD appear to offer unique insights regarding endothelial
      function. The present review describes the techniques used to assess SS-FMD and
      summarizes the evidence regarding 1) SS-FMD as an index of endothelial function
      in humans, highlighting comparisons with RH-FMD, and 2) potential differences in
      shear stress transduction and vasodilator production stimulated by transient
      versus sustained shear stress stimuli. The evidence suggests that SS-FMD is a
      useful tool to assess endothelial function and that further research is required
      to characterize the mechanisms involved and its association with long-term
      cardiovascular outcomes. NEW & NOTEWORTHY Sustained increases in peripheral
      conduit artery shear stress, created via distal skin heating or exercise, provide
      a physiologically relevant stimulus for flow-mediated dilation (FMD). Sustained
      stimulus FMD and FMD stimulated by transient, reactive hyperemia-induced
      increases in shear stress provide distinct assessments of conduit artery
      endothelial function.

PMID- 29167122
TI  - Burst patterning of hypothalamic paraventricular nucleus-driven sympathetic nerve
      activity in ANG II-salt hypertension.
AB  - ANG II-salt hypertension selectively increases splanchnic sympathetic nerve
      activity (sSNA), but the extent to which this reflects increased respiratory
      versus cardiac rhythmic bursting is unknown. Here, integrated sSNA was elevated
      in ANG II-infused rats fed a high-salt (2% NaCl) diet (ANG II-HSD) compared with
      vehicle-infused rats fed a normal-salt (0.4% NaCl) diet (Veh-NSD; P < 0.01).
      Increased sSNA was not accompanied by increased inspiratory or expiratory
      bursting, consistent with no group difference in central inspiratory drive.
      Consistent with preserved inhibitory baroreflex entrainment of elevated sSNA in
      ANG II-HSD rats, the time integral ( P < 0.05) and amplitude ( P < 0.01) of
      cardiac rhythmic sSNA were increased. Consistent with activity of hypothalamic
      paraventricular nucleus (PVN) neurons supporting basal SNA in ANG II-salt
      hypertension, inhibition of PVN with the GABA-A receptor agonist muscimol reduced
      mean arterial pressure (MAP) and integrated sSNA only in the ANG II-HSD group ( P
      < 0.001). PVN inhibition had no effect on respiratory rhythmic sSNA bursting in
      either group but reduced cardiac rhythmic sSNA in ANG II-HSD rats only ( P <
      0.01). The latter likely reflected reduced inhibitory baroreflex entrainment
      subsequent to the fall of MAP. Of note is that MAP as well as integrated and
      rhythmic burst patterns of sSNA were similar in vehicle-infused rats whether they
      were fed a normal or high-salt diet. Findings indicate that PVN neurons support
      elevated sSNA in ANG II-HSD rats by driving a tonic component of activity without
      altering respiratory or cardiac rhythmic bursting. Because sSNA was unchanged in
      Veh-HSD rats, activation of PVN-driven tonic sSNA appears to require central
      actions of ANG II. NEW & NOTEWORTHY ANG II-salt hypertension is strongly
      neurogenic and depends on hypothalamic paraventricular nucleus (PVN)-driven
      splanchnic sympathetic nerve activity (sSNA). Here, respiratory and cardiac
      bursts of sSNA were preserved in ANG II-salt rats and unaltered by PVN
      inhibition, suggesting that PVN neurons drive a tonic component of sSNA rather
      than modulating dominant patterns of burst discharge.

PMID- 29167123
TI  - Lower resting and exercise-induced circulating angiogenic progenitors and
      angiogenic T cells in older men.
AB  - Aging is associated with a dysfunctional endothelial phenotype as well as reduced
      angiogenic capabilities. Exercise exerts beneficial effects on the cardiovascular
      system, possibly by increasing/maintaining the number and/or function of
      circulating angiogenic cells (CACs), which are known to decline with age.
      However, the relationship between cardiorespiratory fitness (CRF) and age-related
      changes in the frequency of CACs, as well as the exercise-induced responsiveness
      of CACs in older individuals, has not yet been determined. One-hundred seven
      healthy male volunteers, aged 18-75 yr, participated in study 1. CRF was
      estimated using a submaximal cycling ergometer test. Circulating endothelial
      progenitor cells (EPCs), angiogenic T cells (TANG), and their chemokine (C-X-C
      motif) receptor 4 (CXCR4) cell surface receptor expression were enumerated by
      flow cytometry using peripheral blood samples obtained under resting conditions
      before the exercise test. In study 2, 17 healthy men (8 young men, 18-25 yr; 9
      older men, 60-75 yr) were recruited, and these participants undertook a 30-min
      cycling exercise bout at 70% maximal O2 consumption, with CACs enumerated before
      and immediately after exercise. Age was inversely associated with both CD34+
      progenitor cells ( r2 = -0.140, P = 0.000) and TANG ( r2 = -0.176, P = 0.000)
      cells as well as CXCR4-expressing CACs (CD34+: r2 = -0.167, P = 0.000; EPCs: r2 =
      -0.098, P = 0.001; TANG: r2 = -0.053, P = 0.015). However, after correcting for
      age, CRF had no relationship with either CAC subset. In addition, older
      individuals displayed attenuated exercise-induced increases in CD34+ progenitor
      cells, TANG, CD4+, TANG, and CD8+CXCR4+ TANG cells. Older men display lower CAC
      levels, which may contribute to increased risk of cardiovascular disease, and
      older adults display an impaired exercise-induced responsiveness of these cells.
      NEW & NOTEWORTHY Older adults display lower circulating progenitor cell and
      angiogenic T cell counts compared with younger individuals independently of
      cardiometabolic risk factors and cardiorespiratory fitness. Older adults also
      display impaired exercise-induced mobilization of these vasculogenic cells.

PMID- 29167124
TI  - Micro-RNA-1 is decreased by hypoxia and contributes to the development of
      pulmonary vascular remodeling via regulation of sphingosine kinase 1.
AB  - Sphingosine kinase 1 (SphK1) upregulation is associated with pathologic pulmonary
      vascular remodeling in pulmonary arterial hypertension (PAH), but the mechanisms
      controlling its expression are undefined. In this study, we sought to
      characterize the regulation of SphK1 expression by micro-RNAs (miRs). In silico
      analysis of the SphK1 3'-untranslated region identified several putative miR
      binding sites, with miR-1-3p (miR-1) being the most highly predicted target.
      Therefore we further investigated the role of miR-1 in modulating SphK1
      expression and characterized its effects on the phenotype of pulmonary artery
      smooth muscle cells (PASMCs) and the development of experimental pulmonary
      hypertension in vivo. Our results demonstrate that miR-1 is downregulated by
      hypoxia in PASMCs and can directly inhibit SphK1 expression. Overexpression of
      miR-1 in human PASMCs inhibits basal and hypoxia-induced proliferation and
      migration. Human PASMCs isolated from PAH patients exhibit reduced miR-1
      expression. We also demonstrate that miR-1 is downregulated in mouse lung tissues
      during experimental hypoxia-mediated pulmonary hypertension (HPH), consistent
      with upregulation of SphK1. Furthermore, administration of miR-1 mimics in vivo
      prevented the development of HPH in mice and attenuated induction of SphK1 in
      PASMCs. These data reveal the importance of miR-1 in regulating SphK1 expression
      during hypoxia in PASMCs. A pivotal role is played by miR-1 in pulmonary vascular
      remodeling, including PASMC proliferation and migration, and its overexpression
      protects from the development of HPH in vivo. These studies improve our
      understanding of the molecular mechanisms underlying the pathogenesis of
      pulmonary hypertension.

PMID- 29167125
TI  - Mesenchymal stem cells reduce hypoxia-induced apoptosis in alveolar epithelial
      cells by modulating HIF and ROS hypoxic signaling.
AB  - Distal lung diseases, such as pulmonary fibrosis or acute lung injury, are
      commonly associated with local alveolar hypoxia that may be deleterious through
      the stimulation of alveolar epithelial cell (AEC) apoptosis. In various murine
      models of alveolar injury, administration of allogenic human mesenchymal stem
      cells (hMSCs) exerts an overall protective paracrine effect, limiting lung
      inflammation and fibrosis. However, the precise mechanisms on lung cells
      themselves remain poorly understood. Here, we investigated whether hMSC
      conditioned medium (hMSC-CM) would protect AECs from hypoxia-induced apoptosis
      and explored the mechanisms involved in this cytoprotective effect. Exposure of
      rat primary AECs to hypoxia (1.5% O2 for 24 h) resulted in hypoxia-inducible
      factor (HIF)-1alpha protein stabilization, partly dependent on reactive oxygen
      species (ROS) accumulation, and in a twofold increase in AEC apoptosis that was
      prevented by the HIF inhibitor 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole
      and the antioxidant drug N-acetyl cysteine. Incubation of AECs with hMSC-CM
      significantly reduced hypoxia-induced apoptosis. hMSC-CM decreased HIF-1alpha
      protein expression, as well as ROS accumulation through an increase in
      antioxidant enzyme activities. Expression of Bnip3 and CHOP, two proapoptotic
      targets of HIF-1alpha and ROS pathways, respectively, was suppressed by hMSC-CM,
      while Bcl-2 expression was restored. The paracrine protective effect of hMSC was
      partly dependent on keratinocyte growth factor and hepatocyte growth factor
      secretion, preventing ROS and HIF-1alpha accumulation.

PMID- 29167127
TI  - HCAHPS survey to measure pain communication, not management.

PMID- 29167126
TI  - Chronic lung injury and impaired pulmonary function in a mouse model of acid
      ceramidase deficiency.
AB  - Farber disease (FD) is a debilitating lysosomal storage disorder (LSD) caused by
      a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene
      ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical
      phenotypes. Severe cases of FD are frequently associated with neurological
      involvement, failure to thrive, and respiratory complications. Mice homozygous (
      Asah1P361R/P361R) for an orthologous patient mutation in Asah1 recapitulate human
      FD. In this study, we show significant impairment in lung function, including low
      compliance and increased airway resistance in a mouse model of ACDase deficiency.
      Impaired lung mechanics in Farber mice resulted in decreased blood oxygenation
      and increased red blood cell production. Inflammatory cells were recruited to
      both perivascular and peribronchial areas of the lung. We observed large
      vacuolated foamy histiocytes that were full of storage material. An increase in
      vascular permeability led to protein leakage, edema, and impacted surfactant
      homeostasis in the lungs of Asah1P361R/P361R mice. Bronchial alveolar lavage
      fluid (BALF) extraction and analysis revealed accumulation of a highly turbid
      lipoprotein-like substance that was composed in part of surfactants,
      phospholipids, and ceramides. The phospholipid composition of BALF from
      Asah1P361R/P361R mice was severely altered, with an increase in both
      phosphatidylethanolamine (PE) and sphingomyelin (SM). Ceramides were also found
      at significantly higher levels in both BALF and lung tissue from Asah1P361R/P361R
      mice when compared with levels from wild-type animals. We demonstrate that a
      deficiency in ACDase leads to sphingolipid and phospholipid imbalance, chronic
      lung injury caused by significant inflammation, and increased vascular
      permeability, leading to impaired lung function.

PMID- 29167128
TI  - REMS standardization moves forward.

PMID- 29167129
TI  - Corrections.

PMID- 29167130
TI  - Corrections.

PMID- 29167131
TI  - Texas pharmacy legend James D. McKinley dies at 93.

PMID- 29167132
TI  - Summaries of safety labeling changes approved by FDA-Boxed warnings highlights,
      July-September 2017.

PMID- 29167133
TI  - ASHP at 75 Years: Celebrating the past and embracing the future.

PMID- 29167134
TI  - Analysis of FDA approvals of targeted anticancer combination regimens.

PMID- 29167135
TI  - Falsely elevated D-dimer level after iron sucrose infusion.

PMID- 29167136
TI  - Impact of a pharmacist-led pneumococcal vaccine compliance program.

PMID- 29167137
TI  - Surviving and thriving under a new director of pharmacy.

PMID- 29167138
TI  - Recent advances in management of autosomal-dominant polycystic kidney disease.
AB  - PURPOSE: Promising developments in the search for effective pharmacotherapies for
      autosomal-dominant polycystic kidney disease (ADPKD) are reviewed. SUMMARY: The
      formation and development of cysts characteristic of ADPKD result in inexorable
      renal and extrarenal manifestations that give rise to more rapid disease
      progression and more widespread complications than are seen with other forms of
      chronic kidney disease. To date, no agent has gained Food and Drug Administration
      marketing approval for use in patients with ADPKD, complicating efforts to meet
      the medical needs of this population. Although definitive ultrasonographic
      diagnostic strategies are available, molecular screening approaches lack
      sufficient evidence and patient outcomes data to support broad clinical
      application. Recently completed and ongoing clinical trials point to a number of
      encouraging platforms for evidence-based ADPKD management. Tolvaptan therapy
      significantly improved cyst burden and slowed disease progression among patients
      with early-stage ADPKD in a large-scale trial, while somatostatin therapies may
      also be useful in halting disease progression and managing comorbid polycystic
      liver disease. Stem cell research and nanomedicine might represent novel
      approaches to gaining comprehensive insights on ADPKD and, ultimately, to
      targeting the disease's origins, thereby making restoration of kidney function
      possible. CONCLUSION: A number of pharmacotherapy approaches to ADPKD management
      show promise but are unlikely to be curative, fueling interest among researchers
      in finding new applications for nanomedicine and stem cell technologies that can
      slow ADPKD progression and better control complications of the disease.

PMID- 29167139
TI  - Development and validation of a complexity score to rank hospitalized patients at
      risk for preventable adverse drug events.
AB  - PURPOSE: The development of risk models for 16 preventable adverse drug events
      (pADEs) and their aggregation into the final complexity score (C-score) are
      described. METHODS: Using data from 2 tertiary care facilities, logistic
      regression models were constructed for the first 5 hospital days that admissions
      were at risk for each of 16 pADEs. The best model for each pADE was validated in
      100 bootstrap samples. The C-score was then aggregated and predicted individual
      pADE risk as the probability to develop at least 1 pADE. Using the 100 bootstrap
      samples for each pADE, 100 C-scores for validation were generated. RESULTS: We
      utilized electronic health records (EHR) data from 65,518 admissions to UF Health
      Shands and 18,269 admissions to UF Health Jacksonville to develop risk models for
      16 pADEs. Most models had very strong discriminant validity (C-statistic > 0.8),
      with the highest predicted decile representing about half of manifest pADEs.
      Among admissions in the highest C-score decile, about two thirds experienced at
      least 1 pADE (C-statistic, 0.838; 95% confidence interval, 0.838-0.839). C-score
      precision, defined as the percentage of patients consistently (i.e., at least 95
      of 100 samples) ranked in the 90th percentile, was 80-84%. CONCLUSION: The C
      score was developed and validated for the identification of hospitalized patients
      at highest risk for pADEs. Aggregation of individual prediction models into a
      single score reduced its predictive power for most pADEs, compared with the
      individual risk models, but concentrated in the highest C-score decile a patient
      group more than two thirds of whom experienced at least 1 pADE.

PMID- 29167140
TI  - Needs assessment for developing a program to help train advanced-practice
      pharmacists for research.
AB  - PURPOSE: Results of a needs assessment to determine priority topics and preferred
      formats for research training in pharmacy residency programs are reported.
      SUMMARY: For pharmacists seeking advanced-practice positions in academia, the
      ability to conduct practice-based research is expected. Pharmacy residency
      programs are a primary recruitment source for these positions, but research
      training varies by residency site and available expertise. To help define the
      optimal content and format of resident research training, ASHP and the ASHP
      Research and Education Foundation conducted a needs assessment targeting
      postgraduate year 1 (PGY1) pharmacy residency directors (RPDs). The response rate
      was 36.5% (271 of 743 invitees); the information obtained was used to guide
      development of a Web-based training series. Only 12% of the RPDs who participated
      in the survey indicated that currently available research training resources
      within their residency programs were sufficient. Sixty-seven percent of surveyed
      RPDs agreed that a Web-based training program would be a useful resource, and 81%
      agreed that the target audience should be pharmacy residents. Training topics of
      greatest interest to RPDs included (1) components of a resident research plan,
      (2) identifying research questions, (3) study design and sample selection, (4)
      project management, (5) data acquisition, cleaning, management, and analysis, and
      (6) presenting and publishing project results. CONCLUSION: This needs assessment
      clearly identified opportunities for improving the infrastructure and content of
      PGY1 residency research training. At a minimum, training programs should focus on
      practice-based research concepts using readily accessible health-system data
      systems and provide universal accessibility and sufficient flexibility to allow
      residency programs to integrate the training in a manner that works best for the
      program.

PMID- 29167141
TI  - Impact of automatic infectious diseases consultation on the management of
      fungemia at a large academic medical center.
AB  - PURPOSE: The impact of automatic infectious diseases (ID) consultation for
      inpatients with fungemia at a large academic medical center was studied. METHODS:
      In this single-center, retrospective study, the time to appropriate antifungal
      therapy before and after implementing a policy requiring automatic ID
      consultation for the management of fungemia for all patients with an inpatient
      positive blood culture for fungus was examined. The rates of ID consultation; the
      likelihood of receiving appropriate antifungal therapy; central venous catheter
      (CVC) removal rates; performance of ophthalmologic examinations; infection
      related length of stay (LOS); rates of all-cause inhospital mortality, death, or
      transfer to an intensive care unit within 7 days of first culture; and inpatient
      cost of antifungals were also evaluated. RESULTS: A total of 173 unique episodes
      (94 and 79 in the control and intervention groups, respectively) were included.
      Candida species were the most frequently cultured organisms, isolated from over
      90% of patients in both groups. No differences were observed between the control
      and intervention groups in time to appropriate therapy, infection-related LOS, or
      time to CVC removal. However, patients in the intervention group were more likely
      than those in the control group to receive appropriate antifungal therapy (p =
      0.0392), undergo ophthalmologic examination (p = 0.003), have their CVC removed
      (p = 0.0038), and receive ID consultation (p = 0.0123). Inpatient antifungal
      costs were significantly higher in the intervention group (p = 0.0177).
      CONCLUSION: While automatic ID consultation for inpatients with fungemia did not
      affect the time to administration of appropriate therapy, improvement was
      observed for several process indicators, including rates of appropriate
      antifungal therapy selection, time to removal of CVCs, and performance of
      ophthalmologic examinations.

PMID- 29167142
TI  - Creating a new rural pharmacy workforce: Development and implementation of the
      Rural Pharmacy Health Initiative.
AB  - PURPOSE: An innovative certificate program aimed at expanding the rural pharmacy
      workforce, increasing the number of pharmacists with expertise in rural practice,
      and improving healthcare outcomes in rural North Carolina is described. SUMMARY:
      Predicted shortages of primary care physicians and closures of critical access
      hospitals are expected to worsen existing health disparities. Experiential
      education in schools and colleges of pharmacy primarily takes place in academic
      medical centers and, unlike experiential education in medical schools, rarely
      emphasizes the provision of patient care in rural U.S. communities, where chronic
      diseases are prevalent and many residents struggle with poverty and poor access
      to healthcare. To help address these issues, UNC Eshelman School of Pharmacy
      developed the 3-year Rural Pharmacy Health Certificate program. The program
      curriculum includes 4 seminar courses, interprofessional education and
      interaction with medical students, embedding of each pharmacy student into a
      specific rural community for the duration of training, longitudinal ambulatory
      care practice experiences, community engagement initiatives, leadership training,
      development and implementation of a population health project, and 5 pharmacy
      practice experiences in rural settings. CONCLUSION: The Rural Pharmacy Health
      Certificate program at UNC Eshelman School of Pharmacy seeks to transform rural
      pharmacy practice by creating a pipeline of rural pharmacy leaders and teaching a
      unique skillset that will be beneficial to healthcare systems, communities, and
      patients.

PMID- 29167143
TI  - Summaries of safety labeling changes approved by FDA-Boxed warnings highlights,
      July-September 2017.

PMID- 29167144
TI  - Efficiency analysis of a barcode-enabled and integrated medication-tracking
      system.
AB  - PURPOSE: Operational efficiency improvements for pharmacy workflow processes were
      evaluated using a barcode-enabled and integrated medication-tracking system for
      medications dispensed from the pharmacy to the emergency department (ED).
      METHODS: The preimplementation study period (Period 1) was defined as November 17
      December 16, 2015; system implementation and training, were defined as December
      17, 2015-January 18, 2016; and postimplementation (Period 2) was defined as
      January 19-February 17, 2016. Periods 1 and 2 were compared to (1) quantify the
      number and type of phone calls received related to medication inquiries, (2)
      evaluate the percentage of redispensed doses per total dispensed doses, and (3)
      assess the rate of medication administration record (MAR) messages received per
      total dispensed doses. RESULTS: A reduction in the total number of phone calls by
      77% was observed (from 125 to 29 calls). A 0.7% difference was detected for re
      dispensed doses as well as MAR messages (0.009% difference in rate) between the 2
      study periods. This difference was observed despite an increase in the total
      amount of dispensed doses that occurred for both redispensed doses (936) and MAR
      messages (920) during Period 2. CONCLUSION: A barcode-enabled and integrated
      medication-tracking system was successfully implemented into the medication
      distribution process in the ED. The process change increased operational pharmacy
      efficiencies by decreasing medication status phone calls, redispensed doses, and
      MAR messages.

PMID- 29167145
TI  - Impact of pharmacist intervention on influenza vaccine assessment and
      documentation in hospitalized psychiatric patients.
AB  - PURPOSE: Results of an initiative to improve assessment and documentation of the
      influenza vaccination status of adult psychiatric inpatients are reported.
      METHODS: A prospective quality-improvement study was conducted at a large,
      tertiary care academic medical center with the aim of improving compliance with
      the Influenza Immunization (IMM-2) quality measure, which was added to the
      Inpatient Psychiatric Facility Quality Reporting (IPFQR) program in 2015 and
      requires assessment and documentation of influenza vaccination status in
      specified groups of psychiatric inpatients. The primary objective was to improve
      the IMM-2 IPFQR compliance rate to 100% during the 2015-16 influenza season from
      a rate of 55% during the 2014-15 influenza season through pharmacist
      interventions; secondary objectives included analysis of types of pharmacist
      interventions, rates of influenza vaccination status assessment and ordering, and
      rates of vaccine refusal by psychiatric disease state. RESULTS: With pharmacist
      interventions, the IMM-2 IPFQR compliance rate was increased to 99% during the
      2015-16 influenza season. Of the 1,413 patients included in the study population,
      45% (n = 646) were targeted for pharmacist intervention. Influenza vaccine was
      ordered for 61% of the study population (n = 867 patients), with an overall
      refusal rate of 74% (n = 642). Differences in refusal rates by psychiatric
      diagnosis were not significant. CONCLUSION: Pharmacist-conducted education of
      nurses and interventions to ensure completion of influenza vaccine assessments
      and documentation led to an improved IMM-2 IPFQR compliance rate at the study
      site.

PMID- 29167146
TI  - Impact of educational intervention on management of periprocedural
      anticoagulation.
AB  - PURPOSE: The effect of education regarding new evidence in periprocedural
      anticoagulation, with a focus on reducing use in patients at only moderate
      thromboembolic risk, is presented. METHODS: A retrospective cohort analysis and
      quasiexperimental design were used. The initial review identified the current
      state of practice regarding bridging anticoagulation. Education was then provided
      to primary care providers and pharmacists on recent evidence. A subsequent review
      was completed to assess the impact of this education on clinical decision-making.
      Inclusion criteria were adults taking warfarin for an indication of mechanical
      heart valve, atrial fibrillation (AF), or history of venous thromboembolism (VTE)
      and required interruption of warfarin therapy to undergo a planned procedure.
      Patients were excluded if their anticoagulation was managed outside of the
      Minneapolis Veterans Affairs Anticoagulation Clinic. RESULTS: The overall rate of
      bridging decreased from 38.8% to 24.8% (14% decrease; 95% confidence interval
      [CI], 2-26%; p = 0.028) confidence interval [CI], 0.02-0.26; p = 0.026) after
      educational intervention. This decrease occurred in the moderate thromboembolic
      risk group, in which the bridging rate decreased from 63.8% to 30.2% (33.6%
      decrease; 95% CI, 14-53%; p = 0.001). Bleeding complications occurred more
      frequently in patients who received bridging. There were no thromboembolic
      complications. CONCLUSION: The majority of patients at moderate thromboembolic
      risk were previously receiving bridging until new evidence was released
      indicating that the risks may outweigh any benefits. The provision of education
      to primary care physicians and pharmacy staff regarding this new evidence in the
      area of periprocedural anticoagulation management significantly reduced the
      amount of bridging used for patients on warfarin for AF or a history of VTE who
      were at moderate thromboembolic risk.

PMID- 29167147
TI  - Medication errors resulting in harm: Using chargemaster data to determine
      association with cost of hospitalization and length of stay.
AB  - PURPOSE: Results of an analysis of the economic impact of adverse drug events
      (ADEs) resulting in patient harm on hospitalization costs and length of stay
      (LOS) are reported. METHODS: In a retrospective single-site study, medication
      errors among patients admitted to an academic medical center during the period
      April 2014-May 2015 were identified using voluntary event reporting system data
      and diagnosis codes. Hospitalization cases involving documented ADEs resulting in
      harm, as defined on a widely used medication error classification index, were
      matched with control cases by admission period, diagnosis-related group, and
      patient age and sex. Total hospitalization costs and LOS in the study groups were
      analyzed using an independent 2-sample Mann-Whitney U test. RESULTS: Among 416
      hospitalization cases evaluated for inclusion in the study, 242 were matched with
      3,279 control cases for analysis. The primary drug classes implicated in the
      evaluated medication errors included chemotherapy agents (38%), corticosteroids
      (14%), and opioids (11%). Total hospitalization costs differed significantly (p =
      0.044) between patients who experienced ADEs resulting in harm (median, $19,444;
      interquartile range [IQR], $13,481-$40,580) and those who did not (median,
      $17,173; IQR, $12,500-$27,125); the former group also had a significantly (p =
      0.005) longer median LOS. CONCLUSION: Chargemaster data for an academic medical
      center revealed that the median total hospitalization cost and LOS were
      significantly greater for hospitalizations during which a harm-causing medication
      error was recorded versus hospitalizations during which harm-causing medication
      errors were not recorded.

PMID- 29167148
TI  - Neonatal cardiomyocyte hypertrophy induced by endothelin-1 is blocked by
      estradiol acting on GPER.
AB  - Estradiol (E2) prevents cardiac hypertrophy, and these protective actions are
      mediated by estrogen receptor (ER)alpha and ERbeta. The G protein-coupled
      estrogen receptor (GPER) mediates many estrogenic effects, and its activation in
      the heart has been observed in ischemia and reperfusion injury or hypertension
      models; however, the underlying mechanisms need to be fully elucidated. Herein,
      we investigated whether the protective effect of E2 against cardiomyocyte
      hypertrophy induced by endothelin-1 (ET-1) is mediated by GPER and the signaling
      pathways involved. Isolated neonatal female rat cardiomyocytes were treated with
      ET-1 (100 nmol/l) for 48 h in the presence or absence of E2 (10 nmol/l) or GPER
      agonist G-1 (10 nmol/l) and GPER antagonist G-15 (10 nmol/l). ET-1 increased the
      surface area of cardiomyocytes, and this was associated with increased expression
      of atrial and brain natriuretic peptides. Additionally, ET-1 increased the
      phosphorylation of extracellular signal-related protein kinases-1/2 (ERK1/2).
      Notably, E2 or G-1 abolished the hypertrophic actions of ET-1, and that was
      reversed by G-15. Likewise, E2 reversed the ET-1-mediated increase of ERK1/2
      phosphorylation as well as the decrease of phosphorylated Akt and its upstream
      activator 3-phosphoinositide-dependent protein kinase-1 (PDK1). These effects
      were inhibited by G-15, indicating that they are GPER dependent. Confirming the
      participation of GPER, siRNA silencing of GPER inhibited the antihypertrophic
      effect of E2. In conclusion, E2 plays a key role in antagonizing ET-1-induced
      hypertrophy in cultured neonatal cardiomyocytes through GPER signaling by a
      mechanism involving activation of the PDK1 pathway, which would prevent the
      increase of ERK1/2 activity and consequently the development of hypertrophy.

PMID- 29167149
TI  - Three-dimensional imaging reveals endo(sarco)plasmic reticulum-containing
      invaginations within the nucleoplasm of muscle.
AB  - The mammalian nucleus has invaginations from the cytoplasm, termed nucleoplasmic
      reticulum (NR). With increased resolution of cellular imaging, progress has been
      made in understanding the formation and function of NR. In fact, nucleoplasmic
      Ca2+ homeostasis has been implicated in the regulation of gene expression, DNA
      repair, and cell death. However, the majority of studies focus on cross-sectional
      or single-plane analyses of NR invaginations, providing an incomplete assessment
      of its distribution and content. Here, we provided advanced imaging and three
      dimensional reconstructive analyses characterizing the molecular constituents of
      nuclear invaginations in the nucleoplasm in HEK293 cells, murine C2C12 muscle
      cells, and cardiac myocytes. We demonstrated the presence of critical Ca2+
      regulatory channels, including sarco(endo)plasmic reticulum Ca2+-ATPase 2a
      (SERCA2a), stromal interaction molecule 1 (STIM1), and Ca2+ release-activated
      Ca2+ channel protein 1 (ORAI1), in the nucleoplasm in isolated primary mouse
      cardiomyocytes. We have shown for the first time the presence of STIM1 and ORAI1
      in the nucleoplasm, suggesting the presence of store-operated calcium entry
      (SOCE) mechanism in nucleoplasmic Ca2+ regulation. These results show that
      nucleoplasmic invaginations contain continuous endoplasmic reticulum components,
      mitochondria, and intact nuclear membranes, highlighting the extremely detailed
      and complex nature of this organellar structure.

PMID- 29167150
TI  - The dawn of succinylation: a posttranslational modification.
AB  - Posttranslational modifications affect almost all proteins and are critical to a
      well-functioning and diverse proteome; however, many modifications remain
      relatively unknown and unstudied. This paper will give a perspective on the
      rapidly developing, novel posttranslational modification called succinylation.
      This modification may be implicated in numerous diseases, such as hepatic,
      cardiac, and pulmonary diseases. Although the influences of this modification
      still remain poorly understood, we are confident that further research into
      succinylation will provide an enhanced understanding of the complex machinery
      within the mitochondria, as well as the imposing consequences associated with its
      dysfunction.

PMID- 29167151
TI  - Substituted-cysteine accessibility and cross-linking identify an exofacial cleft
      in the 7th and 8th helices of the proton-coupled folate transporter (SLC46A1).
AB  - The proton-coupled folate transporter (PCFT-SLC46A1) is required for folate
      transport across the apical membrane of the small intestine and across the
      choroid plexus. This study focuses on the structure/function of the 7th
      transmembrane domain (TMD), and its relationship to the 8th TMD as assessed by
      the substituted cysteine accessibility method (SCAM) and dicysteine cross
      linking. Nine exofacial residues (I278C; H281C-L288C) of 23 residues in the 7th
      TMD were accessible to 2-((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA
      biotin). Pemetrexed, a high-affinity substrate for PCFT, decreased or abolished
      biotinylation of seven of these residues consistent with their location in or
      near the folate binding pocket. Homology models of PCFT based on Glut5 fructose
      transporter structures in both inward- and outward- open conformations were
      constructed and predicted that two pairs of residues (T289-I304C and Q285-Q311C)
      from the 7th and 8th TMDs should be in sufficiently close proximity to form a
      disulfide bond when substituted with cysteines. The single Cys-substituted
      mutants were accessible to MTSEA-biotin and functional with and without
      pretreatment with dithiotreitol. However, the double mutants were either not
      accessible at all, or accessibility was markedly reduced and function markedly
      impaired. This occurred spontaneously without inclusion of an oxidizing agent.
      Dithiotreitol restored accessibility and function consistent with disulfide bond
      disruption. The data establish the proximity of exofacial regions of the 7th and
      8th TMDs and their role in defining the aqueous translocation pathway and suggest
      that these helices may be a component of an exofacial cleft through which
      substrates enter the protein binding pocket in its outward-open conformation.

PMID- 29167152
TI  - RAB27B requirement for stretch-induced exocytosis in bladder umbrella cells.
AB  - Umbrella cells, which must maintain a tight barrier, modulate their apical
      surface area during bladder filling by exocytosis of an abundant, subapical pool
      of discoidal- and/or fusiform-shaped vesicles (DFVs). Despite the importance of
      this trafficking event for bladder function, the pathways that promote DFV
      exocytosis remain to be identified. We previously showed that DFV exocytosis
      depends in part on a RAB11A-RAB8A-MYO5B network, but RAB27B is also reported to
      be associated with DFVs, and knockout mice lacking RAB27B have fewer DFVs.
      However, the RAB27B requirements for DFV exocytosis and the relationship between
      RAB27B and the other umbrella cell-expressed RABs remains unclear. Using a whole
      bladder preparation, we observed that filling-induced exocytosis of human growth
      hormone-loaded DFVs was significantly inhibited when RAB27B expression was
      downregulated using shRNA. RAB27A was also expressed in rat urothelium; however,
      RAB27A-specific shRNAs did not inhibit exocytosis, and the combination of RAB27A
      and RAB27B shRNAs did not significantly affect DFV exocytosis more than treatment
      with RAB27B shRNA alone. RAB27B and RAB11A showed a small degree of overlap when
      quantified using Squassh segmentation software, and expression of dominant-active
      or dominant-negative mutants of RAB11A or RAB8A, or expression of a RAB11A
      specific shRNA, had no significant effect on the size, number, or intensity of
      RAB27B-positive DFVs. Likewise, treatment with RAB27B-specific shRNA had no
      effect on RAB11A-positive DFV parameters. We conclude that RAB27B, but not
      RAB27A, regulates DFV exocytosis in bladder umbrella cells in a manner that may
      be parallel to the previously described RAB11A-RAB8A-MYO5B pathway.

PMID- 29167153
TI  - French surgeon is struck off after "actively disengaging from the regulatory
      process".

PMID- 29167154
TI  - Implementation of the EULAR cardiovascular risk management guideline in patients
      with rheumatoid arthritis: results of a successful collaboration between primary
      and secondary care.
AB  - The updated European League Against Rheumatism (EULAR) guideline recommends
      cardiovascular disease (CVD) risk assessment at least once every 5 years in all
      patients with rheumatoid arthritis (RA). This viewpoint starts with a literature
      overview of studies that investigated the level of CVD risk factor (CVD-RF)
      screening in patients with RA in general practices or in outpatient clinics.
      These studies indicate that CVD-RF screening in patients with RA is marginally
      applied in clinical practice, in primary as well as secondary care. Therefore,
      the second part of this viewpoint describes an example of the successful
      implementation of the EULAR cardiovascular disease risk management (CVRM)
      guideline in patients with RA in a region in the south of the Netherlands where
      rheumatologists and general practitioners (GPs) closely collaborate to manage the
      cardiovascular risk of patients with RA. The different components of this
      collaboration and the responsibilities of respectively primary and secondary care
      professionals are described. Within this collaboration, lipid profile was used as
      an indicator to assess whether CVD-RF screening was performed in the previous 5
      years. In 72% (n=454) of the 628 patients with RA, a lipid profile was determined
      in the previous 5 years. As part of routine quality control, a reminder was sent
      to the GP in case a patient with RA was not screened. After sending the reminder
      letter, in 88% of all patients with RA, CVD risk assessment was performed. This
      collaboration can be seen as good practice to provide care in line with the EULAR
      guideline.

PMID- 29167155
TI  - We need to change the culture around complaints procedures.

PMID- 29167156
TI  - Rapid root responses of seedlings exposed to a postdrought water pulse.
AB  - PREMISE OF THE STUDY: Mediterranean-type climate ecosystems experience
      significant variability in precipitation within and across years and may be
      characterized by periods of extreme drought followed by a brief, high-intensity
      precipitation pulse. Rapid root growth could be a key factor in effective
      utilization of precipitation pulses, leading to higher rates of seedling
      establishment. Changes in root growth rate are rarely studied, however, and
      patterns in seedling root traits are not well explored. We investigated the
      influence of an extreme postdrought precipitation event on seedlings that occur
      in southern California coastal sage scrub. METHODS: We measured root elongation
      rate, root tip appearance rate, new leaf appearance rate, and canopy growth rate
      on 18 mediterranean species from three growth forms. KEY RESULTS: Root elongation
      rate responded more strongly to the precipitation pulse than did root tip
      appearance rate and either metric of aboveground growth. The majority of species
      exhibited a significant change in root growth rate within 1 week of the pulse.
      Responses varied in rapidity and magnitude across species, however, and were not
      generally predictable based on growth form. CONCLUSIONS: While the majority of
      species exhibited shifts in belowground growth following the pulse, the direction
      and magnitude of these morphological responses were highly variable within growth
      form. Understanding the implications of these different response strategies for
      plant fitness is a crucial next step to forecasting community dynamics within
      ecosystems characterized by resource pulses.

PMID- 29167157
TI  - Bipolar distributions in vascular plants: A review.
AB  - Bipolar disjunct distributions are a fascinating biogeographic pattern exhibited
      by about 30 vascular plants, whose populations reach very high latitudes in the
      northern and southern hemispheres. In this review, we first propose a new
      framework for the definition of bipolar disjunctions and then reformulate a list
      of guiding principles to consider how to study bipolar species. Vicariance and
      convergent evolution hypotheses have been argued to explain the origin of this
      fragmented distribution pattern, but we show here that they can be rejected for
      all bipolar species, except for Carex microglochin Instead, human introduction
      and dispersal (either direct or by mountain-hopping)-facilitated by standard and
      nonstandard vectors-are the most likely explanations for the origin of bipolar
      plant disjunctions. Successful establishment after dispersal is key for
      colonization of the disjunct areas and appear to be related to both intrinsic
      (e.g., self-compatibility) and extrinsic (mutualistic and antagonistic
      interactions) characteristics. Most studies on plant bipolar disjunctions have
      been conducted in Carex (Cyperaceae), the genus of vascular plants with the
      largest number of bipolar species. We found a predominant north-to-south
      direction of dispersal, with an estimated time of diversification in agreement
      with major cooling events during the Pliocene and Pleistocene. Bipolar Carex
      species do not seem to depend on specialized traits for long-distance dispersal
      and could have dispersed through one or multiple stochastic events, with birds as
      the most likely dispersal vector.

PMID- 29167158
TI  - Observations on bipolar disjunctions of moonwort ferns (Botrychium,
      Ophioglossaceae).
AB  - Peter Raven, in 1963, included two fern taxa of the genus Botrychium in his list
      of plant species exhibiting American amphitropical bipolar disjunctions. He
      attributed the southern hemisphere occurrences to post-Pleistocene long-distance
      dispersal from counterparts in the northern hemisphere, probably assisted by
      annual bird migrations between the disjunct areas. Using genetic evidence
      gathered through worldwide analyses of phylogenetic relationship in Botrychium,
      we now review and reconsider Raven's conclusions. Genetic similarities indicate
      that South American Botrychium dusenii is an allotetraploid taxon closely related
      to B. spathulatum, a North American endemic, and that B. lunaria in New Zealand
      possesses a genotype identical to that of a taxon in North America derived
      through introgressive hybridization between B. lunaria and an endemic North
      American species, B. neolunaria Both North American counterparts exhibit Raven's
      characteristics of bipolar disjuncts in their occurrence in mountain and coastal
      meadows, copious production of small propagules (spores in Botrychium),
      occurrence in habitats frequented by transpolar bird migrants, and ability to
      found new colonies through inbreeding. We discuss these characteristics in
      Botrychium and relative to other ferns and suggest further studies on Botrychium
      and related taxa to address questions of time, number, and mode of bipolar
      dispersals.

PMID- 29167159
TI  - Niche shifts after long-distance dispersal events in bipolar sedges (Carex,
      Cyperaceae).
AB  - PREMISE OF THE STUDY: Bipolar species represent the greatest biogeographical
      disjunction on Earth, raising many questions about the colonization and adaptive
      processes behind such striking distribution. We investigated climatic niche
      differences of five Carex bipolar species in North and South America to assess
      niche shifts between these two regions. Moreover, we assessed potential
      distribution changes with future climate change. METHODS: We used 1202 presence
      data points from herbarium specimens and 19 bioclimatic variables to assess
      climatic niche differences and potential distributions among the five species
      using ordination methods and Maxent. KEY RESULTS: The niche overlap analyses
      showed low levels of niche filling and high climatic niche expansion between
      North and South America. Carex macloviana and C. maritima showed the greatest
      niche expansion (60% and 96%, respectively), followed by C. magellanica (45%) and
      C. microglochin (39%). Only C. canescens did not colonize new environments (niche
      expansion = 0.2%). In contrast, all species but C. magellanica had niche filling
      that was <40%; hence, they are absent in the south from many environments they
      inhabit in North America. Climate change will push all species toward higher
      latitudes and elevation, reducing the availability of suitable environments.
      CONCLUSIONS: The colonization of South America seems to have involved frequent
      climatic niche shifts. Most species have colonized new environments from those
      occupied in the North. Observed niche shifts appear congruent with time since
      colonization and with current genetic structure within species. In these cold
      dwelling species, climate change will most likely decrease their suitable
      environments in the future.

PMID- 29167160
TI  - Persistent pollinators and the evolution of complete selfing.

PMID- 29167161
TI  - Inferring long-distance dispersal modes in American amphitropically disjunct
      species through adaptive dispersal structures.
AB  - PREMISE OF THE STUDY: A repeated pattern of American amphitropical disjunct
      species or sister species distributed on either side of the equator has long
      fascinated botanists, but the modes of these disjunctions remain untested. We
      evaluated diaspore morphology to generate hypotheses on probable dispersal
      mechanisms. METHODS: The sizes and structures of diaspores, habit, habitat,
      distribution, and dispersal units were collected for 108 species from literature
      searches and herbarium specimens. Variation was evaluated with summary
      statistics, chi2 tests with Monte Carlo simulations, ANOVAs, and the
      nonparametric Mann-Whitney test. KEY RESULTS: Seeds were the dispersing diaspore
      in 38.0% of the species, 45.4 were dispersed as fruits, and the remaining were
      dispersed as infructescences or spores. Diaspores were epizoochorous (52.8%),
      anemochorous (20.4%), achorous (15.7%), endozoochorous (8.3%), and hydrochorous
      (2.8%). Epizoochory was significantly greater than expected. Zoochory occurred
      more frequently than expected when considering achorous diaspores as animal
      dispersed. Most species were associated with wetland, woodland, and grassland
      habitats. An ANOVA revealed that diaspores associated with hydrochory were larger
      and anemochory was smaller; all other syndromes were not significantly different.
      CONCLUSIONS: Botanists have long-held the assumption that bird migrations are
      responsible for amphitropical disjunctions. Our results support this hypothesis,
      with the majority of these events occurring by external attachment of small
      fruits. However, our results also indicate that anemochory might play a greater
      role in producing amphitropical distributions than previously thought and at a
      greater rate than endozoochory or hydrochory.

PMID- 29167162
TI  - Naturally fragmented and isolated distribution in subtropical grassland patches
      affects genetic diversity and structure at different spatial scales: The case of
      Tibouchina hatschbachii, an endemic shrub from Brazil.
AB  - PREMISE OF THE STUDY: The genetic structure of organisms results from the
      interactions between life history traits and the ecological and demographic
      characteristics of the landscape that shape the intra- and interpopulation
      genetic variation in space and time. In this study, we used a species restricted
      to islands of grassland vegetation in southern Brazil to investigate the effects
      of its naturally fragmented distribution on diversity and genetic structure
      patterns. METHODS: Diversity and intra- and interpopulational genetic structure
      were analyzed using polymorphisms of eight nuclear microsatellite markers in 205
      individuals of T. hatschbachii and Bayesian and multivariate methods. KEY
      RESULTS: At the intrapopulation level, populations presented low genetic
      diversity and strong spatial genetic structure, indicating a greater spatial
      autocorrelation until ~50-500 m. At the interpopulation level, genetic variation
      partitioned into two geographically structured genetic clusters. Gene flow
      through pollen was more efficient than gene flow by seeds. CONCLUSIONS: Genetic
      structure was influenced locally by seed and pollen dispersal dynamics and
      regionally by fragmentation of the grassland landscape. This study highlights the
      importance of geological barriers, and potentially a role for genetic drift, in
      influencing diversification of species in subtropical grasslands of southern
      Brazil.

PMID- 29167163
TI  - Menstrual myths, morals and milestones: a paediatric miasma.

PMID- 29167164
TI  - NRF2 prevents hypertension, increased ADMA, microvascular oxidative stress, and
      dysfunction in mice with two weeks of ANG II infusion.
AB  - Nuclear factor erythyroid factor 2 (Nrf2) transcribes genes in cultured
      endothelial cells that reduce reactive oxygen species (ROS) and generate nitric
      oxide (NO) or metabolize asymmetric dimethylarginine (ADMA), which inhibits NO
      synthase (NOS). Therefore, we undertook a functional study to test the hypothesis
      that activation of Nrf2 by tert-butylhydroquinone (tBHQ) preserves microvascular
      endothelial function during oxidative stress. Wild-type CB57BL/6 (wt), Nrf2 wt
      (+/+), or knockout (-/-) mice received vehicle (Veh) or tBHQ (0.1%; activator of
      Nrf2) during 14-day infusions of ANG II (to induce oxidative stress) or sham. MAP
      was recorded by telemetry. Mesenteric resistance arterioles were studied on
      isometric myographs and vascular NO and ROS by fluorescence microscopy. ANG II
      increased the mean arterial pressure (112 +/- 5 vs. 145 +/- 5 mmHg; P < 0.01) and
      excretion of 8-isoprostane F2alpha (2.8 +/- 0.3 vs. 3.8 +/- 0.3 ng/mg creatinine;
      P < 0.05) at 12-14 days. However, 12 days of ANG II reduced endothelium-derived
      relaxation (27 +/- 5 vs. 17 +/- 3%; P < 0.01) and NO (0.38 +/- 0.07 vs. 0.18 +/-
      0.03 units; P < 0.01) but increased microvascular remodeling, endothelium-derived
      contractions (7.5 +/- 0.5 vs. 13.0 +/- 1.7%; P < 0.01), superoxide (0.09 +/- 0.03
      vs. 0.29 +/- 0.08 units; P < 0.05), and contractions to U-46,619 (87 +/- 6 vs.
      118 +/- 3%; P < 0.05), and endothelin-1(89 +/- 4 vs. 123 +/- 12%; P < 0.05). tBHQ
      prevented all of these effects of ANG II at 12-14 days in Nrf2+/+ mice but not in
      Nrf2-/- mice. In conclusion, tBHQ activates Nrf2 to prevent microvascular
      endothelial dysfunction, remodeling, and contractility, and moderate ADMA and
      hypertension at 12-14 days of ANG II infusion, thereby preserving endothelial
      function and preventing hypertension.

PMID- 29167165
TI  - Long-term high-altitude hypoxia influences pulmonary arterial L-type calcium
      channel-mediated Ca2+ signals and contraction in fetal and adult sheep.
AB  - Long-term hypoxia (LTH) has a profound effect on pulmonary arterial
      vasoconstriction in the fetus and adult. Dysregulation in Ca2+ signaling is
      important during the development of LTH-induced pulmonary hypertension. In the
      present study, we tested the hypothesis that L-type Ca2+ channels (CaL), which
      are voltage dependent and found in smooth, skeletal, and cardiac muscle, are
      important in the adaptation of pulmonary arterial contractions in postnatal
      maturation and in response to LTH. Pulmonary arteries were isolated from fetal or
      adult sheep maintained at low or high altitude (3,801 m) for >100 days. The
      effects were measured using an L-type Ca2+ channel opener FPL 64176 (FPL) in the
      presence or absence of an inhibitor, Nifedipine (NIF) on arterial contractions,
      intracellular Ca2+ oscillations, and ryanodine receptor-driven Ca2+ sparks. FPL
      induced pulmonary arterial contractions in all groups were sensitive to NIF.
      However, when compared with 125 mM K+, FPL contractions were greater in fetuses
      than in adults. FPL reduced Ca2+ oscillations in myocytes of adult but not fetal
      arteries, independently of altitude. The FPL effects on Ca2+ oscillations were
      reversed by NIF in myocytes of hypoxic but not normoxic adults. FPL failed to
      enhance Ca2+ spark frequency and had little impact on spatiotemporal firing
      characteristics. These data suggest that CaL-dependent contractions are largely
      uncoupled from intracellular Ca2+ oscillations and the development of Ca2+
      sparks. This raises questions regarding the coupling of pulmonary arterial
      contractility to membrane depolarization, attendant CaL facilitation, and the
      related associations with the activation of Ca2+ oscillations and Ca2+ sparks.

PMID- 29167166
TI  - Blood-borne interleukin-1beta acts on the subfornical organ to upregulate the
      sympathoexcitatory milieu of the hypothalamic paraventricular nucleus.
AB  - We previously reported that microinjection of the proinflammatory cytokine
      interleukin-1beta (IL-1beta) into the subfornical organ (SFO) elicits a pressor
      response accompanied by increases in inflammation and renin-angiotensin system
      (RAS) activity in the SFO and hypothalamic paraventricular nucleus (PVN). The
      present study sought to determine whether blood-borne IL-1beta induces similar
      neurochemical changes in the SFO and PVN and, if so, whether increased
      inflammation and RAS activity at the SFO level orchestrate the sympathoexcitatory
      response to circulating IL-1beta. In urethane-anesthetized male Sprague-Dawley
      rats, intravenous injection of IL-1beta (500 ng) increased blood pressure, heart
      rate, renal sympathetic nerve activity, and mRNA for angiotensin-converting
      enzyme, angiotensin II type 1a receptor, cyclooxygenase-2, tumor necrosis factor
      alpha, and IL-1beta, as well as the tumor necrosis factor-alpha p55 receptor and
      the IL-1 receptor, in the SFO and PVN. Pretreatment with SFO microinjections of
      the angiotensin II type 1a receptor blocker losartan (1 ug), the angiotensin
      converting enzyme inhibitor captopril (1 ug), or the cyclooxygenase-2 inhibitor
      NS-398 (2 ug) attenuated expression of these excitatory mediators in the SFO and
      downstream in the PVN and the IL-1beta-induced pressor responses. An SFO lesion
      minimized the IL-1beta-induced expression of inflammatory and RAS components as
      well as c-Fos, an indicator of neuronal excitation, in the PVN. These studies
      demonstrate that circulating IL-1beta, which increases in cardiovascular
      disorders such as hypertension and heart failure, acts on the SFO to increase
      inflammation and RAS activity in the SFO and PVN and that intervening in these
      neurochemical processes in the SFO can significantly reduce the sympathetic
      response.

PMID- 29167168
TI  - Coffee gets a clean bill of health.

PMID- 29167169
TI  - Cutting-edge microangio-CT: new dimensions in vascular imaging and kidney
      morphometry.
AB  - In the last decades, the contrast-enhanced micro-computed tomography (micro-CT)
      imaging of a whole animal kidney became increasingly important. The visualization
      was mainly limited to middle-sized vessels. Since modern desktop micro-CT
      scanners provide the necessary detail resolution, we developed an approach for
      rapid visualization and consistent assessment of kidney vasculature and glomeruli
      number. This method is based on MUAngiofil, a new polymerizing contrast agent
      with homogenous X-ray absorption, which provides continuous filling of the
      complete vasculature and enables correlative imaging approaches. For rapid and
      reliable kidney morphometry, the microangio-CT (uaCT) data sets from glial cell
      line-derived neurotrophic factor (GDNF)+/- mice and their wild-type littermates
      were used. The results were obtained much faster compared with the current gold
      standard, histology-based stereology, and without processing artifacts. The
      histology-based morphometry was done afterward on the same kidneys. Both
      approaches revealed that the GDNF+/- male mice had about 40% fewer glomeruli.
      Furthermore, our approach allows for the definition of sites of interest for
      further histological investigation, i.e., correlative morphology. The polymerized
      MUAngiofil stays in perfused vessels and is autofluorescent, which is what
      greatly facilitates the matching of histological sections with uaCT data. The
      presented approach is a time-efficient, reliable, qualitative, and quantitative
      methodology. Besides glomerular morphometry, the uaCT data can be used for
      qualitative and quantitative analysis of the kidney vasculature and correlative
      morphology.

PMID- 29167167
TI  - Cellular mechanisms underlying obesity-induced arterial stiffness.
AB  - Obesity is an emerging pandemic driven by consumption of a diet rich in fat and
      highly refined carbohydrates (a Western diet) and a sedentary lifestyle in both
      children and adults. There is mounting evidence that arterial stiffness in
      obesity is an independent and strong predictor of cardiovascular disease (CVD),
      cognitive functional decline, and chronic kidney disease. Cardiovascular
      stiffness is a precursor to atherosclerosis, systolic hypertension, cardiac
      diastolic dysfunction, and impairment of coronary and cerebral flow. Moreover,
      premenopausal women lose the CVD protection normally afforded to them in the
      setting of obesity, insulin resistance, and diabetes, and this loss of CVD
      protection is inextricably linked to an increased propensity for arterial
      stiffness. Stiffness of endothelial and vascular smooth muscle cells,
      extracellular matrix remodeling, perivascular adipose tissue inflammation, and
      immune cell dysfunction contribute to the development of arterial stiffness in
      obesity. Enhanced endothelial cortical stiffness decreases endothelial generation
      of nitric oxide, and increased oxidative stress promotes destruction of nitric
      oxide. Our research over the past 5 years has underscored an important role of
      increased aldosterone and vascular mineralocorticoid receptor activation in
      driving development of cardiovascular stiffness, especially in females consuming
      a Western diet. In this review the cellular mechanisms of obesity-associated
      arterial stiffness are highlighted.

PMID- 29167170
TI  - Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota
      composition in a chronic kidney disease mouse model.
AB  - Accumulation of uremic toxins, which exert deleterious effects in chronic kidney
      disease, is influenced by the intestinal environment; the microbiota contributes
      to the production of representative uremic toxins, including p-cresyl sulfate and
      indoxyl sulfate. Canagliflozin is a sodium-glucose cotransporter (SGLT) 2
      inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition
      of intestinal SGLT1 can influence the gastrointestinal environment. We examined
      the effect of canagliflozin on the accumulation of uremic toxins in chronic
      kidney disease using adenine-induced renal failure mice. Two-week canagliflozin
      (10 mg/kg po) treatment did not influence the impaired renal function; however,
      it significantly reduced the plasma levels of p-cresyl sulfate and indoxyl
      sulfate in renal failure mice (a 75% and 26% reduction, respectively, compared
      with the vehicle group). Additionally, canagliflozin significantly increased
      cecal short-chain fatty acids in the mice, suggesting the promotion of bacterial
      carbohydrate fermentation in the intestine. Analysis of the cecal microbiota
      showed that canagliflozin significantly altered microbiota composition in the
      renal failure mice. These results indicate that canagliflozin exerts intestinal
      effects that reduce the accumulation of uremic toxins including p-cresyl sulfate.
      Reduction of accumulated uremic toxins by canagliflozin could provide a potential
      therapeutic option in chronic kidney disease.

PMID- 29167171
TI  - Advances in our understanding of the pathogenesis of hemolytic uremic syndromes.
AB  - Hemolytic uremic syndrome (HUS) is major global health care issue as it is the
      leading cause of acute kidney injury in children. It is a triad of acute kidney
      injury, microangiopathic hemolytic anemia, and thrombocytopenia. In recent years,
      major advances in our understanding of complement-driven inherited rare forms of
      HUS have been achieved. However, in children 90% of cases of HUS are associated
      with a Shiga toxin-producing enteric pathogen. The precise pathological
      mechanisms in this setting are yet to be elucidated. The purpose of this review
      is to discuss advances in our understanding of the pathophysiology underlying HUS
      and identify the key questions yet to be answered by the scientific community.

PMID- 29167172
TI  - Podocytes exhibit a specialized protein quality control employing derlin-2 in
      kidney disease.
AB  - Podocytes are terminally differentiated cells of the kidney filtration barrier
      with a limited proliferative capacity and are the primary glomerular target for
      various sources of cellular stress. Accordingly, it is particularly important for
      podocytes to cope with stress efficiently to circumvent cell death and avoid
      compromising renal function. Improperly folded proteins within the endoplasmic
      reticulum (ER) are associated with increased cellular injury and cell death. To
      relieve ER stress, protein quality control mechanisms like ER-associated
      degradation (ERAD) are initiated. Derlin-2 is an important dislocation channel
      component in the ERAD pathway, having an indispensable role in clearing misfolded
      glycoproteins from the ER lumen. With studies linking ER stress to kidney
      disease, we investigated the role of derlin-2 in the susceptibility of podocytes
      to injury due to protein misfolding. We show that podocytes employ derlin-2 to
      mediate the ER quality control system to maintain cellular homeostasis in both
      mouse and human glomeruli. Patients with focal segmental glomerulosclerosis
      (FSGS) or diabetic nephropathy (DN) upregulate derlin-2 expression in response to
      glomerular injury, as do corresponding mouse models. In derlin-2-deficient
      podocytes, compensatory responses were lost under adriamycin (ADR)-induced ER
      dysfunction, and severe cellular injury ensued via a caspase-12-dependent
      pathway. Moreover, derlin-2 overexpression in vitro attenuated ADR-induced
      podocyte injury. Thus derlin-2 is part of a protein quality control mechanism
      that can rescue glomerular injury attributable to impaired protein folding
      pathways in the ER. Induction of derlin-2 expression in vivo may have
      applications in prevention and treatment of glomerular diseases.

PMID- 29167174
TI  - Inherited bone marrow failure syndromes: considerations pre- and posttransplant.
AB  - Patients with inherited bone marrow failure syndromes are usually identified when
      they develop hematologic complications such as severe bone marrow failure,
      myelodysplastic syndrome, or acute myeloid leukemia. They often have specific
      birth defects or other physical abnormalities that suggest a syndrome, and
      sequencing of specific genes or next-generation sequencing can determine or
      confirm the particular syndrome. The 4 most frequent syndromes are Fanconi
      anemia, dyskeratosis congenita, Diamond Blackfan anemia, and Shwachman Diamond
      syndrome. This review discusses the major complications that develop as the
      patients with these syndromes age, as well as additional late effects following
      hematopoietic stem cell transplantation. The most common complications are iron
      overload in transfused patients and syndrome-specific malignancies in
      untransplanted patients, which may occur earlier and with higher risks in those
      who have received transplants.

PMID- 29167175
TI  - Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma.
AB  - Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which
      rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an
      extensive but ineffective inflammatory/immune cell infiltrate. This striking
      feature suggests that malignant HRS cells escape immunosurveillance and interact
      with immune cells in the cancer microenvironment for survival and growth. We
      previously found that cHLs have a genetic basis for immune evasion: near-uniform
      copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci,
      CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number-dependent increased expression of
      these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1
      receptor-positive immune effectors in the tumor microenvironment and induce PD-1
      signaling and associated immune evasion. The genetic bases of enhanced PD-1
      signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.

PMID- 29167176
TI  - The addition of IMiDs for patients with daratumumab-refractory multiple myeloma
      can overcome refractoriness to both agents.

PMID- 29167177
TI  - Smoothened signaling in the mouse osteoblastoid lineage is required for efficient
      B lymphopoiesis.
AB  - The stromal signals that promote B lymphopoiesis remain poorly understood.
      Hedgehog (Hh) signaling promotes B lymphopoiesis in a non-cell-autonomous fashion
      in vitro, and depletion of the Hh effector Smoothened (Smo) from stromal cells is
      associated with the loss of osteoblastoid markers. These observations suggested
      that Hh signaling in the osteoblastoid lineage promotes B lymphopoiesis in vivo.
      To test this, we employed a mouse model for conditional ablation of Smo in the
      osteoblastoid lineage. Depletion of Smo from osteoblastoid cells is associated
      with profound and selective reductions in the number and proportion of bone
      marrow B-lymphoid progenitors. Upon partial bone marrow ablation, mutant animals
      exhibit delayed repopulation of the B-lymphoid compartment after the early
      lymphoid progenitor stage. Primary osteoblasts from mutant mice are defective in
      supporting B lymphopoiesis in vitro, whereas hematopoietic progenitors from
      mutant mice exhibit normal differentiation. We conclude that efficient B
      lymphopoiesis in vivo is dependent on the maintenance of Hh signaling in the
      osteoblastoid lineage.

PMID- 29167178
TI  - MAIT cells: a novel therapeutic target for alcoholic liver disease?

PMID- 29167181
TI  - A new model for an old friend.
AB  - JGP study suggests the anion exchanger AE1 operates via an elevator-like
      mechanism.

PMID- 29167179
TI  - Proteinopathies and OXPHOS dysfunction in neurodegenerative diseases.
AB  - Mitochondria participate in essential processes in the nervous system such as
      energy and intermediate metabolism, calcium homeostasis, and apoptosis. Major
      neurodegenerative diseases are characterized pathologically by accumulation of
      misfolded proteins as a result of gene mutations or abnormal protein homeostasis.
      Misfolded proteins associate with mitochondria, forming oligomeric and fibrillary
      aggregates. As mitochondrial dysfunction, particularly of the oxidative
      phosphorylation system (OXPHOS), occurs in neurodegeneration, it is postulated
      that such defects are caused by the accumulation of misfolded proteins. However,
      this hypothesis and the pathological role of proteinopathies in mitochondria
      remain elusive. In this study, we critically review the proposed mechanisms
      whereby exemplary misfolded proteins associate with mitochondria and their
      consequences on OXPHOS.

PMID- 29167180
TI  - Asymmetry of inverted-topology repeats in the AE1 anion exchanger suggests an
      elevator-like mechanism.
AB  - The membrane transporter anion exchanger 1 (AE1), or band 3, is a key component
      in the processes of carbon-dioxide transport in the blood and urinary
      acidification in the renal collecting duct. In both erythrocytes and the
      basolateral membrane of the collecting-duct alpha-intercalated cells, the role of
      AE1 is to catalyze a one-for-one exchange of chloride for bicarbonate. After
      decades of biochemical and functional studies, the structure of the transmembrane
      region of AE1, which catalyzes the anion-exchange reaction, has finally been
      determined. Each protomer of the AE1 dimer comprises two repeats with inverted
      transmembrane topologies, but the structures of these repeats differ. This
      asymmetry causes the putative substrate-binding site to be exposed only to the
      extracellular space, consistent with the expectation that anion exchange occurs
      via an alternating-access mechanism. Here, we hypothesize that the unknown,
      inward-facing conformation results from inversion of this asymmetry, and we
      propose a model of this state constructed using repeat-swap homology modeling. By
      comparing this inward-facing model with the outward-facing experimental
      structure, we predict that the mechanism of AE1 involves an elevator-like motion
      of the substrate-binding domain relative to the nearly stationary dimerization
      domain and to the membrane plane. This hypothesis is in qualitative agreement
      with a wide range of biochemical and functional data, which we review in detail,
      and suggests new avenues of experimentation.

PMID- 29167182
TI  - TSC2 rare germline variants in non-tuberous sclerosis patients with
      neuroendocrine neoplasias.

PMID- 29167183
TI  - Evolution of subclinical myocardial dysfunction detected by two-dimensional and
      three-dimensional speckle tracking in asymptomatic type 1 diabetic patients: a
      long-term follow-up study.
AB  - BACKGROUND: We sought to assess the long-term evolution of left ventricular (LV)
      function using two-dimensional (2D) and three-dimensional (3D) speckle tracking
      echocardiography (STE) for the detection of preclinical diabetic cardiomyopathy,
      in asymptomatic type 1 diabetic patients, over a 6-year follow-up. DESIGN AND
      METHODS: Sixty-six asymptomatic type 1 diabetic patients with no cardiovascular
      risk factors were compared to 26 matched healthy controls. Conventional, 2D and
      3D-STE were performed at baseline. A subgroup of 14 patients underwent a 6-year
      follow-up evaluation. RESULTS: At baseline, diabetic patients had similar LV
      ejection fraction (60 vs 61%; P = NS), but impaired longitudinal function, as
      assessed by 2D-global longitudinal strain (GLS) (-18.9 +/- 2 vs -20.5 +/- 2; P =
      0.0002) and 3D-GLS (-17.5 +/- 2 vs -19 +/- 2; P = 0.003). At follow-up, diabetic
      patients had worsened longitudinal function compared to baseline (2D-GLS: -18.4
      +/- 1 vs -19.2 +/- 1; P = 0.03). Global circumferential (GCS) and radial (GRS)
      strains were unchanged at baseline and during follow-up. Metabolic status did not
      correlate with GLS, whereas GCS and GRS showed a good correlation, suggestive of
      a compensatory increase of circumferential and radial functions in advanced
      stages of the disease - long-term diabetes (GCS: -26 +/- 3 vs -23.3 +/- 3; P =
      0.008) and in the presence of microvascular complications (GRS: 38.8 +/- 9 vs
      34.3 +/- 8; P = 0.04). CONCLUSIONS: Subclinical myocardial dysfunction can be
      detected by 2D and 3D-STE in type 1 diabetic patients, independently of any other
      cardiovascular risk factors. Diabetic cardiomyopathy progression was suggested by
      a mild decrease in longitudinal function at the follow-up, but did not extend to
      a clinical expression of the disease, as no death or over heart failure was
      reported.

PMID- 29167184
TI  - Retrobulbar heavy liquid discovered 5 years postvitrectomy.

PMID- 29167185
TI  - Hyperacute leucopenia associated with furosemide.
AB  - A 72-year-old man presented to the hospital with exacerbation of congestive heart
      failure. He was given furosemide 40 mg intravenously twice at 4 hours apart. At 4
      hours after the second dose of furosemide, his white blood cells (WBC) dropped
      acutely from 9.8 to 2.4*109/L (reference range 4.1 to 9.3*109/L). With the
      discontinuation of furosemide, the WBC trended up to 7.1*109/L about 13 hours
      after the second dose of intravenous furosemide and remained in normal range for
      the next 3 days. However, when the oral furosemide was started on hospital day 4,
      there was a mild drop in WBC count, which returned to and maintained at baseline
      since the next day. The dynamic changes in the patient's WBC were coincident with
      the use of furosemide. The possible mechanisms of furosemide-associated transient
      hyperacute leucopenia were discussed.

PMID- 29167186
TI  - Giant insulinoma: an unusual cause of hypoglycaemia.

PMID- 29167187
TI  - Ischaemic pituitary tumour apoplexy and concurrent meningitis: a diagnostic
      dilemma.
AB  - Pituitary tumour apoplexy is a rare but potentially life threatening clinical
      syndrome that mostly results from haemorrhage in the pre-existent tumour. Pure
      ischaemic subtype of apoplexy is even rarer. The presentation can be hard to
      differentiate clinically from bacterial meningitis. Moreover, the presence of one
      does not necessarily exclude the other and early diagnosis of both conditions is
      imperative for timely management. We report a case of ischaemic pituitary tumour
      apoplexy that may have precipitated in the setting of bacterial meningitis.

PMID- 29167188
TI  - Severe panniculitis and polyarthritis caused by acinar cell carcinoma arising
      from an ectopic pancreas.
AB  - The pancreatitis, panniculitis and polyarthritis (PPP) syndrome is a rare
      condition caused by pancreatic diseases, such as acute or chronic pancreatitis or
      pancreatic carcinoma. We report the first case of PPP syndrome caused by
      metastatic acinar cell carcinoma from an ectopic pancreas. The symptoms were
      successfully managed by the treatment of the metastatic carcinoma. Pancreatic
      cytosteatonecrosis should be always considered in a patient who is showing
      symptoms of panniculitis and polyarthritis.

PMID- 29167190
TI  - An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental
      Glomerulosclerosis.
AB  - BACKGROUND AND OBJECTIVES: Proteinuria is used as an indicator of FSGS disease
      activity, but its use as a clinical trial end point is not universally accepted.
      The goal of this study was to refine proteinuria definitions associated with long
      term kidney survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data on 466
      patients with primary FSGS with proteinuria (urine protein-to-creatinine ratio >1
      g/g) were analyzed from five independent cohorts. Proteinuria by months 1, 4, and
      8 after study baseline was categorized by conventional definitions of complete
      (<0.3 g/g) and partial remission (<3.5 g/g and 50% reduction in proteinuria).
      Novel remission definitions were explored using receiver operating curves. Kaplan
      Meier methods were used to estimate the associations of proteinuria with
      progression to ESRD or a 50% loss in kidney function. Propensity score-adjusted
      Cox proportional hazards models were used to adjust for baseline proteinuria,
      eGFR, and therapy. RESULTS: In the initial derivation cohort, conventional
      partial remission was not associated with kidney survival. A novel definition of
      partial remission (40% proteinuria reduction and proteinuria<1.5 g/g) on the
      basis of receiver operating curve analyses of 89 patients was identified
      (Sensitivity=0.70; Specificity=0.77). In the validation cohort analyses, complete
      remission was associated with better prognosis (6 out of 41 patients progressed
      to kidney failure; 6.6 per 100 patient-years) as was the novel partial remission
      (13 out of 71 progressed; 8.5 per 100 patient-years), compared with those with no
      response (51 out of 116 progressed; 20.1 per 100 patient-years). Conventional
      partial remission at month 8, but not month 4, was also associated with better
      response (19 out of 85 patients progressed; risk=10.4 per 100 patient-years).
      Propensity score-adjusted analyses showed the novel partial remission was
      associated with less progression at months 4 and 8 (month 4: hazard ratio, 0.50;
      P=0.01; month 8: hazard ratio, 0.30; P=0.002). CONCLUSIONS: Reaching either a
      complete or partial remission using a novel or conventional definition was
      associated with better long-term outcomes in patients with FSGS. PODCAST: This
      article contains a podcast at https://www.asn
      online.org/media/podcast/CJASN/2018_02_20_CJASNPodcast_18_3_T.mp3.

PMID- 29167191
TI  - Nutritional status plays a crucial role in the mortality of critically ill
      patients with acute renal failure.
AB  - We aimed to clarify associations between nutritional status and mortality in
      patients with acute renal failure. De-identified data were obtained from the
      Medical Information Mart for Intensive Care III database comprising more than
      40,000 critical care patients treated at Beth Israel Deaconess Medical
      Centerbetween 2001 and 2012. Weight loss and body mass index criteria were used
      to define malnutrition. Data of 193 critically ill patients with acute renal
      failure were analyzed, including demographics, nutrition intervention, laboratory
      results, and disease severity. Main outcomes were in-hospital and 1-year
      mortality. The 1-year mortality was significantly higher in those with
      malnutrition than in those without malnutrition (50.0% vs 29.3%, p=0.010), but
      differences in in-hospital survival were not significant (p=0.255). Significant
      differences in mortality were found between those with malnutrition and without
      starting at the 52nd day after intensive care unit (ICU) discharge (p=0.036). No
      significant differences were found between men and women with malnutrition in in
      hospital mortality (p=0.949) and 1-year mortality (p=0.051). Male patients
      requiring intervention with blood products/colloid supplements had greater risk
      of 1-year mortality, but without statistical significance. Nutritional status is
      a predictive factor for mortality among critically ill patients with acute renal
      failure, particularly 1-year mortality after ICU discharge.

PMID- 29167189
TI  - Photobiomodulation Inhibits Long-term Structural and Functional Lesions of
      Diabetic Retinopathy.
AB  - Previous studies demonstrated that brief (3 to 4 min) daily application of light
      at 670 nm to diabetic rodents inhibited molecular and pathophysiologic processes
      implicated in the pathogenesis of diabetic retinopathy (DR) and reversed diabetic
      macular edema in small numbers of patients studied. Whether or not this therapy
      would inhibit the neural and vascular lesions that characterize the early stages
      of the retinopathy was unknown. We administered photobiomodulation (PBM) therapy
      daily for 8 months to streptozotocin-diabetic mice and assessed effects of PBM on
      visual function, retinal capillary permeability, and capillary degeneration using
      published methods. Vitamin D receptor and Cyp24a1 transcripts were quantified by
      quantitative real-time PCR, and the abundance of c-Kit+ stem cells in blood and
      retina were assessed. Long-term daily administration of PBM significantly
      inhibited the diabetes-induced leakage and degeneration of retinal capillaries
      and also significantly inhibited the diabetes-induced reduction in visual
      function. PBM also inhibited diabetes-induced reductions in retinal Cyp24a1 mRNA
      levels and numbers of circulating stem cells (CD45-/c-Kit+), but these effects
      may not account for the beneficial effects of PBM on the retinopathy. PBM
      significantly inhibits the functional and histopathologic features of early DR,
      and these effects likely are mediated via multiple mechanisms.

PMID- 29167192
TI  - Cytokeratin-18 and enhanced liver fibrosis scores in type 1 and type 2 diabetes
      and effects of two different insulins.
AB  - Data on cytokeratin-18 (K-18) and enhanced liver fibrosis (ELF) score in insulin
      treated diabetes patients with non-alcoholic fatty liver disease (NAFLD) are
      limited. This study analyzed phase III data comparing basal insulin peglispro
      (BIL) and insulin glargine in type 1 (T1D), and type 2 diabetes (T2D) (insulin
      naive and insulin-treated). Alanine aminotransferase (ALT), K-18, ELF scores and
      liver fat content (LFC), measured by MRI, were obtained longitudinally. Baseline
      K-18 (U/L) was higher in T2D (range: 207-247) than T1D (range: 148-183),
      correlated with ALT in all populations (r (range) 0.264-0.637, p<0.05), but with
      LFC only in T2D (r (range) 0.474-0.586, p<0.05). K-18 increased significantly
      from baseline in BIL-treated, but not glargine-treated patients. Change from
      baseline (CFB) K-18 was significantly correlated with CFB in ALT in BIL-treated
      T2D populations. Baseline ELF scores were higher in T2D (range: 9.12-9.20) than
      T1D (range: 8.24-8.36), correlated with ALT in T1D only (0.209, p<0.05), and not
      correlated with LFC in any population. ELF scores increased significantly from
      baseline in BIL-treated but not glargine-treated patients. There were no
      correlations between CFB in LFC and ELF score at week 52 in any treatment
      group/population. In all BIL-treated populations, CFB in ALT and CFB in ELF score
      at week 52 were positively correlated. These data characterize associations of K
      18 and ELF score with ALT and LFC in insulin-treated patients with T1D and T2D.
      Hepatopreferential insulins may be associated with increased K-18 and ELF scores
      but mechanisms and clinical significance are unknown. ClinicalTrials.gov
      identifiers are NCT01481779, NCT01435616, NCT01454284 and NCT01582451.

PMID- 29167193
TI  - Airway transplantation of adipose stem cells protects against bleomycin-induced
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease
      with poor prognosis. Adipose-derived stem cells (ADSC) have demonstrated
      regenerative properties in several tissues. The hypothesis of this study was that
      airway transplantation of ADSC could protect against bleomycin (BLM)-induced
      pulmonary fibrosis (PF). Fifty-eight lungs from 29 male Sprague-Dawley rats were
      analyzed. Animals were randomly divided into five groups: a) control (n=3); b)
      sham (n=6); c) BLM (n=6); d) BLM+ADSC-2d (n=6); and e) BLM+ADSC-14d (n=8).
      Animals received 500 uL saline (sham), 2.5 UI/kg BLM in 500 uL saline (BLM), and
      2*106 ADSC in 100 uL saline intratracheally at 2 (BLM+ADSC-2d) and 14 days
      (BLM+ADSC-14d) after BLM. Animals were sacrificed at 28 days. Blinded Ashcroft
      score was used to determine pulmonary fibrosis extent on histology. Hsp27, Vegf,
      Nfkbeta, IL-1, IL-6, Col4, and Tgfbeta1 mRNA gene expression were determined
      using real-time quantitative-PCR. Ashcroft index was: control=0; sham=0.37+/
      0.07; BLM=6.55+/-0.34 vs sham (P=0.006). BLM vs BLM+ADSC-2d=4.63+/-0.38 (P=0.005)
      and BLM+ADSC-14d=3.77+/-0.46 (P=0.005). BLM vs sham significantly increased Hsp27
      (P=0.018), Nfkbeta (P=0.009), Col4 (P=0.004), Tgfbeta1 (P=0.006) and decreased IL
      1 (P=0.006). BLM+ADSC-2d vs BLM significantly decreased Hsp27 (P=0.009) and
      increased Vegf (P=0.006), Nfkbeta (P=0.009). BLM+ADSC-14d vs BLM significantly
      decreased Hsp27 (P=0.028), IL-6 (P=0.013), Col4 (P=0.002), and increased Nfkbeta
      (P=0.040) and Tgfbeta1 (P=0.002). Airway transplantation of ADSC significantly
      decreased the fibrosis rate in both early and established pulmonary fibrosis,
      modulating the expression of Hsp27, Vegfa, Nfkbeta, IL-6, Col4, and Tgfbeta1.
      From a translational perspective, this technique could become a new adjuvant
      treatment for patients with IPF.

PMID- 29167194
TI  - Cardiac Troponin T Increase in Patients with Acute Ischemic Stroke with and
      without Cancer.

PMID- 29167195
TI  - Shoring up DNA methylation and H3K27me3 domain demarcation at developmental
      genes.

PMID- 29167196
TI  - Decreasing incidence of retinopathy of prematurity requiring treatment.

PMID- 29167197
TI  - Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are
      ineffective against malaria infection.
AB  - Antibodies against the central repeat of the Plasmodium falciparum (Pf)
      circumsporozoite protein (CSP) inhibit parasite activity and correlate with
      protection from malaria. However, the humoral response to the PfCSP C terminus (C
      PfCSP) is less well characterized. Here, we describe B cell responses to C-PfCSP
      from European donors who underwent immunization with live Pf sporozoites (PfSPZ
      Challenge) under chloroquine prophylaxis (PfSPZ-CVac), and were protected against
      controlled human malaria infection. Out of 215 PfCSP-reactive monoclonal
      antibodies, only two unique antibodies were specific for C-PfCSP, highlighting
      the rare occurrence of C-PfCSP-reactive B cells in PfSPZ-CVac-induced protective
      immunity. These two antibodies showed poor sporozoite binding and weak inhibition
      of parasite traversal and development, and did not protect mice from infection
      with PfCSP transgenic Plasmodium berghei sporozoites. Structural analyses
      demonstrated that one antibody interacts with a polymorphic region overlapping
      two T cell epitopes, suggesting that variability in C-PfCSP may benefit parasite
      escape from humoral and cellular immunity. Our data identify important features
      underlying C-PfCSP shortcomings as a vaccine target.

PMID- 29167198
TI  - Comparative transcriptome analysis reveals conserved branching morphogenesis
      related genes involved in chamber formation of catfish swimbladder.
AB  - The swimbladder is an internal gas-filled organ in teleosts. Its major function
      is to regulate buoyancy. The swimbladder exhibits great variation in size, shape,
      and number of compartments or chambers among teleosts. However, genomic control
      of swimbladder variation is unknown. Channel catfish ( Ictalurus punctatus), blue
      catfish ( Ictalurus furcatus), and their F1 hybrids of female channel catfish *
      male blue catfish (C * B hybrid catfish) provide a good model in which to
      investigate the swimbladder morphology, because channel catfish possess a single
      chambered swimbladder, whereas blue catfish possess a bichambered swimbladder; C
      * B hybrid catfish possess a bichambered swimbladder but with a significantly
      reduced posterior chamber. Here we determined the transcriptional profiles of
      swimbladder from channel catfish, blue catfish, and C * B hybrid catfish. We
      examined their transcriptomes at both the fingerling and adult stages. Through
      comparative transcriptome analysis, ~4,000 differentially expressed genes (DEGs)
      were identified. Among these DEGs, members of the Wnt signaling pathway ( wnt1,
      wnt2, nfatc1, rac2), Hedgehog signaling pathway ( shh), and growth factors (
      fgf10, igf-1) were identified. As these genes were known to be important for
      branching morphogenesis of mammalian lung and of mammary glands, their
      association with budding of the posterior chamber primordium and progressive
      development of bichambered swimbladder in fish suggest that these branching
      morphogenesis-related genes and their functions in branching are evolutionarily
      conserved across a broad spectrum of species.

PMID- 29167199
TI  - The Germline-Specific Factor OEF-1 Facilitates Coordinated Progression Through
      Germ Cell Development in Caenorhabditis elegans.
AB  - The purpose of germ cells is to ensure the faithful transmission of genetic
      material to the next generation. To develop into mature gametes, germ cells must
      pass through cell cycle checkpoints while maintaining totipotency and genomic
      integrity. How germ cells coordinate developmental events while simultaneously
      protecting their unique fate is not well understood. Here, we characterize a
      novel nuclear protein, Oocyte-Excluded Factor-1 (OEF-1), with highly specific
      germline expression in Caenorhabditis elegans OEF-1 is initially detected early
      in embryogenesis and is expressed in the nuclei of all germ cells during larval
      stages. In adults, OEF-1 expression abruptly decreases just prior to oocyte
      differentiation. In oef-1 mutants, the developmental progression of germ cells is
      accelerated, resulting in subtle defects at multiple stages of germ cell
      development. Lastly, OEF-1 is primarily associated with the bodies of germline
      expressed genes, and as such is excluded from the X chromosome. We hypothesize
      that OEF-1 may regulate the rate of progression through germ cell development,
      providing insight into how these critical maturation events are coordinated.

PMID- 29167200
TI  - Assessing the Relationship of Ancient and Modern Populations.
AB  - Genetic material sequenced from ancient samples is revolutionizing our
      understanding of the recent evolutionary past. However, ancient DNA is often
      degraded, resulting in low coverage, error-prone sequencing. Several solutions
      exist to this problem, ranging from simple approach, such as selecting a read at
      random for each site, to more complicated approaches involving genotype
      likelihoods. In this work, we present a novel method for assessing the
      relationship of an ancient sample with a modern population, while accounting for
      sequencing error and postmortem damage by analyzing raw reads from multiple
      ancient individuals simultaneously. We show that, when analyzing SNP data, it is
      better to sequence more ancient samples to low coverage: two samples sequenced to
      0.5* coverage provide better resolution than a single sample sequenced to 2*
      coverage. We also examined the power to detect whether an ancient sample is
      directly ancestral to a modern population, finding that, with even a few high
      coverage individuals, even ancient samples that are very slightly diverged from
      the modern population can be detected with ease. When we applied our approach to
      European samples, we found that no ancient samples represent direct ancestors of
      modern Europeans. We also found that, as shown previously, the most ancient
      Europeans appear to have had the smallest effective population sizes, indicating
      a role for agriculture in modern population growth.

PMID- 29167201
TI  - Commentaries on Viewpoint: Origin of the forward-going "backward" wave.

PMID- 29167202
TI  - Last Word on Viewpoint: Origin of the forward-going "backward" wave.

PMID- 29167203
TI  - Muscle Oxygen content at exercise in patients with claudication.

PMID- 29167204
TI  - Reply to Drs. Henni and Abraham: Muscle oxygen content at exercise in patients
      with claudication.

PMID- 29167205
TI  - Inaccuracies in caffeine intake quantification and other important limitations in
      recent publication by Goncalves et al.

PMID- 29167206
TI  - Reply to Areta et al.: Time to withdraw and let the myth rest.

PMID- 29167207
TI  - It is time to investigate acute and chronic perceptual responses to eccentric
      cycling.

PMID- 29167208
TI  - Reply to Drs. Pageaux et al.: Cognitive demand of eccentric versus concentric
      cycling.

PMID- 29167209
TI  - Editorial makes unsubstantiated claims about high-load resistance training.

PMID- 29167210
TI  - Reply to Drs. Nuzzo and Barry.

PMID- 29167211
TI  - CORRIGENDUM.

PMID- 29167212
TI  - Cardiovascular Disease, Cancer, and Mortality Among People With Type 2 Diabetes
      and Alcoholic or Nonalcoholic Fatty Liver Disease Hospital Admission.
AB  - OBJECTIVE: To describe associations between alcoholic liver disease (ALD) or
      nonalcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular
      disease (CVD), cancer, and mortality in people with type 2 diabetes mellitus
      (T2DM). RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study by
      using linked population-based routine data from diabetes registry, hospital,
      cancer, and death records for people aged 40-89 years diagnosed with T2DM in
      Scotland between 2004 and 2013 who had one or more hospital admission records.
      Liver disease and outcomes were identified by using ICD-9 and ICD-10 codes. We
      estimated hazard ratios (HRs) from Cox proportional hazards regression models,
      adjusting for key risk factors. RESULTS: A total of 134,368 people with T2DM
      (1,707 with ALD and 1,452 with NAFLD) were studied, with a mean follow-up of 4.3
      years for CVD and 4.7 years for mortality. Among those with ALD, NAFLD, or
      without liver disease hospital records 378, 320, and 21,873 CVD events; 268, 176,
      and 15,101 cancers; and 724, 221, and 16,203 deaths were reported, respectively.
      For ALD and NAFLD, respectively, adjusted HRs (95% CIs) compared with the group
      with no record of liver disease were 1.59 (1.43, 1.76) and 1.70 (1.52, 1.90) for
      CVD, 40.3 (28.8, 56.5) and 19.12 (11.71, 31.2) for hepatocellular carcinoma
      (HCC), 1.28 (1.12, 1.47) and 1.10 (0.94, 1.29) for non-HCC cancer, and 4.86
      (4.50, 5.24) and 1.60 (1.40, 1.83) for all-cause mortality. CONCLUSIONS: Hospital
      records of ALD or NAFLD are associated to varying degrees with an increased risk
      of CVD, cancer, and mortality among people with T2DM.

PMID- 29167214
TI  - Pushing beyond the limit: a novel clinical sign of thoracic aortic dissection.
AB  - The timely diagnosis of aortic dissection is notoriously confounded by unreliable
      symptomatology. We present a previously unreported clinical sign: thoracic pain
      reproduced by abdominal palpation. Our case illustrates the dependence of
      traditional clinical features on the anatomical location of an aortic dissection
      and lends weight to the concept of aortic pain as being a dynamic product of
      inter-related changes in intraluminal pressure, volume, wall stress and diameter.
      The clinical sign we describe may be very specific of acute aortic pathology.

PMID- 29167215
TI  - Mid-aortic syndrome secondary to Takayasu's disease.
AB  - A 24-year-old young woman with good past health presented with hypertension
      during body check. Blood erythrocyte sedimentary rate level was elevated. CT and
      MR angiography revealed moderate stenosis of abdominal aorta and bilaterally
      renal arteries. She was diagnosed with mid-aortic syndrome caused by Takayasu
      arteritis based on clinical, radiological and pathological findings. She was
      treated with abdominal aorta resection, graft replacement and aorta-renal bypass.
      Pathology was compatible with Takayasu arteritis. Postoperatively, her blood
      pressure was normalised. She was prescribed with long-term prednisolone and
      aspirin for her arteritis.

PMID- 29167213
TI  - Interaction of Dietary and Genetic Factors Influencing Body Iron Status and Risk
      of Type 2 Diabetes Within the EPIC-InterAct Study.
AB  - OBJECTIVE: Meat intake has been consistently shown to be positively associated
      with incident type 2 diabetes. Part of that association may be mediated by body
      iron status, which is influenced by genetic factors. We aimed to test for
      interactions of genetic and dietary factors influencing body iron status in
      relation to the risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS:
      The case-cohort comprised 9,347 case subjects and 12,301 subcohort participants
      from eight European countries. Single nucleotide polymorphisms (SNPs) were
      selected from genome-wide association studies on iron status biomarkers and
      candidate gene studies. A ferritin-related gene score was constructed.
      Multiplicative and additive interactions of heme iron and SNPs as well as the
      gene score were evaluated using Cox proportional hazards regression. RESULTS:
      Higher heme iron intake (per 1 SD) was associated with higher ferritin levels
      (beta = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (-0.019 [-0.043;
      0.006]) or transferrin saturation (0.016 [-0.006; 0.037]). Five SNPs located in
      four genes (rs1799945 [HFE H63D], rs1800562 [HFE C282Y], rs236918 [PCK7],
      rs744653 [SLC40A1], and rs855791 [TMPRSS6 V736A]) were associated with ferritin.
      We did not detect an interaction of heme iron and the gene score on the risk of
      diabetes in the overall study population (Padd = 0.16, Pmult = 0.21) but did
      detect a trend toward a negative interaction in men (Padd = 0.04, Pmult = 0.03).
      CONCLUSIONS: We found no convincing evidence that the interplay of dietary and
      genetic factors related to body iron status associates with type 2 diabetes risk
      above the level expected from the sum or product of the two individual exposures.

PMID- 29167216
TI  - A rare case of dual diagnosis in a 16-year-old girl with shortness of breath.
AB  - Pneumothorax and pulmonary embolism (PE) are two life-threatening causes of
      shortness of breath in patients presenting to the emergency department. A rare
      but more serious presentation is that of simultaneous PE and pneumothorax. We
      present the case of a young patient, with no known comorbidities, who presented
      with simultaneous submassive PE and pneumothorax. We will review how these two
      diagnoses may be related, consider the implications of having this dual diagnosis
      on the patient's management and review the current evidence surrounding
      thrombolysis in submassive PE.

PMID- 29167217
TI  - 5-FU-induced leukoencephalopathy with reversible lesion of splenium of corpus
      callosum in a patient with colorectal cancer.
AB  - 5-Fluorouracil (5-FU), a commonly used antimetabolite and antineoplastic agent,
      has been approved for treatment of various cancers. Neurotoxicities are
      considered extremely rare side effects of 5-FU. We present a case of 5-FU-induced
      encephalopathy with diffusion-restricted reversible lesion of the splenium of the
      corpus callosum in a patient with colorectal cancer. The patient presented with
      confusion, dysarthria and agitation after 5-FU infusion. The prognosis of this
      toxic effects of 5-FU is usually good if recognised and treated in time.
      Emergency physicians, general practitioners and oncologists should be aware of
      this rare side effects of 5-FU chemotherapy and its diagnosis and treatment.

PMID- 29167218
TI  - Concomitant AIDS cholangiopathy and Fanconi syndrome as complications of HIV in a
      single patient.
AB  - We describe the case of a 50-year-old woman presenting to our acute medicine
      department with generalised non-specific symptoms on a background of HIV managed
      on triple therapy (tenofovir, lamivudine and zidovudine). On admission, she was
      noted to be acidotic with proteinuria, glycosuria, hypophosphataemia and
      generalised body pain, and was diagnosed with Fanconi's renotubular syndrome
      secondary to tenofovir. It was also noted that she had elevated liver dysfunction
      markers, and an MRI of the liver revealed a focal stricture near the ampulla of
      Vater, resulting in a diagnosis of AIDS cholangiopathy. These two diagnoses are
      rare complications of HIV, and the presence of both these pathologies in a single
      patient has never been reported in the literature before, and we therefore
      believe that this case is the first of its kind.

PMID- 29167219
TI  - Ingestion of nine metallic nails with corrosive: what happened next?
AB  - A 20-year-old woman was brought to the surgery emergency department with the
      complaint of epigastric pain since 1 day following ingestion of multiple metallic
      nails with a cup full of toilet cleaner (corrosive acid) with a suicidal
      intention. Physical examination was essentially unremarkable, and the abdomen
      showed no signs of perforation peritonitis. X-rays of the abdomen showed multiple
      'nail'-like radiopaque shadows in the abdominal cavity with no evidence of free
      gas under the domes of the diaphragm. A non-operative expectant management was
      pursued. The patient had passed all the sharps in stools without any complication
      and was discharged after 12 days. After 3 weeks, the patient presented with non
      bilious vomiting. Further investigations revealed pyloric stenosis with no
      oesophageal luminal stenosis. To bypass the pyloric stenosis, a Billroth II
      gastrojejunostomy was performed. The postoperative period was uneventful, and the
      recovery was smooth.

PMID- 29167220
TI  - Iatrogenic injury of vertebral artery resulting in stroke after central venous
      line insertion.
AB  - There are many complications of central venous catheter insertion. Iatrogenic
      injury of the vertebral artery is a rare complication that can result in severe
      morbidity and mortality. The case presented describes the complication of an
      acute ischaemic stroke after cannulation of the vertebral artery. There are
      various techniques when obtaining central access, however the best practice as
      described by the evidence based guidelines produced by the American Society of
      Anesthesiologists utilises real-time ultrasound guidance to minimise adverse
      events.

PMID- 29167221
TI  - Cervical oesophageal perforation secondary to food consumption in a well
      appearing patient.
AB  - A 71-year-old woman presented to the emergency department 8 days after ingesting
      fish with mild neck pain but otherwise demonstrated no signs of infection. X-rays
      were negative but CT imaging demonstrated a curvilinear radiodense object
      extending from the posterior cervical oesophagus through the right thyroid lobe
      terminating in the neck just a few millimetres from the external carotid artery.
      Rigid oesophagoscopy and direct laryngoscopy were negative and the neck was
      explored for the foreign body, which ultimately was encountered after a
      painstaking dissection of the right neck that included skeletonisation of the
      recurrent laryngeal nerve. Her postoperative recovery was uneventful and after a
      3-day course of intravenous antibiotics she was discharged on oral antibiotics,
      in good condition and tolerating a soft diet.

PMID- 29167222
TI  - Capsule endoscopy in the diagnosis of disseminated Mycobacterium avium complex
      infection.

PMID- 29167223
TI  - Graduate Training at the Interface of Computational and Experimental Biology: An
      Outcome Report from a Partnership of Volunteers between a University and a
      National Laboratory.
AB  - Leading voices in the biological sciences have called for a transformation in
      graduate education leading to the PhD degree. One area commonly singled out for
      growth and innovation is cross-training in computational science. In 1998, the
      University of Tennessee (UT) founded an intercollegiate graduate program called
      the UT-ORNL Graduate School of Genome Science and Technology in partnership with
      the nearby Oak Ridge National Laboratory. Here, we report outcome data that
      attest to the program's effectiveness in graduating computationally enabled
      biologists for diverse careers. Among 77 PhD graduates since 2003, the majority
      came with traditional degrees in the biological sciences, yet two-thirds moved
      into computational or hybrid (computational-experimental) positions. We describe
      the curriculum of the program and how it has changed. We also summarize how the
      program seeks to establish cohesion between computational and experimental
      biologists. This type of program can respond flexibly and dynamically to unmet
      training needs. In conclusion, this study from a flagship, state-supported
      university may serve as a reference point for creating a stable, degree-granting,
      interdepartmental graduate program in computational biology and allied areas.

PMID- 29167224
TI  - Implementation of a Learning Assistant Program Improves Student Performance on
      Higher-Order Assessments.
AB  - Learning assistant (LA) programs have been implemented at a range of
      institutions, usually as part of a comprehensive curricular transformation
      accompanied by a pedagogical switch to active learning. While this shift in
      pedagogy has led to increased student learning gains, the positive effect of LAs
      has not yet been distinguished from that of active learning. To determine the
      effect that LAs would have beyond a student-centered instructional modality that
      integrated active learning, we introduced an LA program into a large-enrollment
      introductory molecular biology course that had already undergone a pedagogical
      transformation to a highly structured, flipped (HSF) format. We used questions
      from a concept test (CT) and exams to compare student performance in LA-supported
      HSF courses with student performance in courses without LAs. Students in the LA
      supported course did perform better on exam questions common to both HSF course
      modalities but not on the CT. In particular, LA-supported students' scores were
      higher on common exam questions requiring higher-order cognitive skills, which
      LAs were trained to foster. Additionally, underrepresented minority (URM)
      students particularly benefited from LA implementation. These findings suggest
      that LAs may provide additional learning benefits to students beyond the use of
      active learning, especially for URM students.

PMID- 29167225
TI  - A Call to Use Cultural Competence When Teaching Evolution to Religious College
      Students: Introducing Religious Cultural Competence in Evolution Education
      (ReCCEE).
AB  - Low acceptance of evolution among undergraduate students is common and is best
      predicted by religious beliefs. Decreasing students' perceived conflict between
      religion and evolution could increase their acceptance of evolution. However,
      college biology instructors may struggle with trying to decrease students'
      perceived conflict between religion and evolution because of differences in the
      religious cultures and beliefs of instructors and students. Although a large
      percentage of undergraduate students in evolution courses are religious, most
      instructors teaching evolution are not. To consider differences between the
      secular culture of many college instructors and the religious culture of many
      students, we propose using a lens of cultural competence to create effective
      evolution education. Cultural competence is the ability of individuals from one
      culture (in this case, primarily secular instructors who are teaching evolution)
      to bridge cultural differences and effectively communicate with individuals from
      a different culture (in this case, primarily religious undergraduate biology
      students). We call this new framework Religious Cultural Competence in Evolution
      Education (ReCCEE). In this essay, we describe a suite of culturally competent
      practices that can help instructors reduce students' perceived conflict between
      evolution and religion, increase students' acceptance of evolution, and help
      create more inclusive undergraduate biology classrooms.

PMID- 29167226
TI  - Surgical Enlargement of the Aortic Root Does Not Increase the Operative Risk of
      Aortic Valve Replacement.
AB  - BACKGROUND: Surgical aortic root enlargement (ARE) during aortic valve
      replacement (AVR) allows for larger prosthesis implantation and may be an
      important adjunct to surgical AVR in the transcatheter valve-in-valve era. The
      incremental operative risk of adding ARE to AVR has not been established. We
      aimed to evaluate the early outcomes of patients undergoing AVR with or without
      ARE. METHODS: From January 1990 to August 2014, 7039 patients underwent AVR
      (AVR+ARE, n=1854; AVR, n=5185) at a single institution. Patients with aortic
      dissection and active endocarditis were excluded. Mean age was 65+/-14 years and
      63% were male. Logistic regression and propensity score matching were used to
      adjust for unbalanced variables in group comparisons. RESULTS: Patients
      undergoing AVR+ARE were more likely to be female (46% versus 34%, P<0.001) and
      had higher rates of previous cardiac surgery (18% versus 12%, P<0.001), chronic
      obstructive pulmonary disease (5% versus 3%, P=0.004), urgent/emergent status (6%
      versus 4%, P=0.01), and worse New York Heart Association status (P<0.001). Most
      patients received bioprosthetic valves (AVR+ARE: 73.4% versus AVR: 73.3%, P=0.98)
      and also underwent concomitant cardiac procedures (AVR+ARE: 68% versus AVR: 67%,
      P=0.31). Mean prosthesis size implanted was slightly smaller in patients
      requiring AVR+ARE versus AVR (23.4+/-2.1 versus 24.1+/-2.3, P<0.001). In-hospital
      mortality was higher after AVR+ARE (4.3% versus 3.0%, P=0.008), although when the
      cohort was restricted to patients undergoing isolated aortic valve replacement
      with or without root enlargement, mortality was not statistically different
      (AVR+ARE: 1.7% versus AVR: 1.1%, P=0.29). After adjustment for baseline
      characteristics, AVR+ARE was not associated with an increased risk of in-hospital
      mortality when compared with AVR (odds ratio, 1.03; 95% confidence interval, 0.75
      1.41; P=0.85). Furthermore, AVR+ARE was not associated with an increased risk of
      postoperative adverse events. Results were similar if propensity matching was
      used instead of multivariable adjustments for baseline characteristics.
      CONCLUSIONS: In the largest analysis to date, ARE was not associated with
      increased risk of mortality or adverse events. Surgical ARE is a safe adjunct to
      AVR in the modern era.

PMID- 29167227
TI  - Pericardial Adipose Tissue Regulates Granulopoiesis, Fibrosis, and Cardiac
      Function After Myocardial Infarction.
AB  - BACKGROUND: The pericardial adipose tissue (AT) contains a high density of
      lymphoid clusters. It is unknown whether these clusters play a role in post
      myocardial infarction (MI) inflammatory responses and cardiac outcome. METHODS:
      Lymphoid clusters were examined in epicardial AT of humans with or without
      coronary artery disease. Murine pericardial lymphoid clusters were visualized in
      mice subjected to coronary artery ligation. To study the relevance of pericardial
      clusters during inflammatory responses after MI, we surgically removed the
      pericardial AT and performed B-cell depletion and granulocyte-macrophage colony
      stimulating factor blockade. Leukocytes in murine hearts, pericardial AT, spleen,
      mediastinal lymph nodes, and bone marrow were quantified by flow cytometry.
      Cannabinoid receptor CB2 (CB2-/-) mice were used as a model for enhanced B-cell
      responses. The effect of impaired dendritic cell (DC) trafficking on pericardial
      AT inflammatory responses was tested in CCR7-/- mice subjected to MI. Cardiac
      fibrosis and ventricular function were assessed by histology and
      echocardiography. RESULTS: We identified larger B-cell clusters in epicardial AT
      of human patients with coronary artery disease in comparison with controls
      without coronary artery disease. Infarcted mice also had larger pericardial
      clusters and 3-fold upregulated numbers of granulocyte-macrophage colony
      stimulating factor-producing B cells within pericardial AT, but not spleen or
      lymph nodes. This was associated with higher DC and T-cell counts in pericardial
      AT, which outnumbered DCs and T cells in lymph nodes. Analysis of DC maturation
      markers, tracking experiments with fluorescently labeled cells, and use of CCR7
      deficient mice suggested that activated DCs migrate from infarcts into
      pericardial AT via CCR7. B-cell depletion or granulocyte-macrophage colony
      stimulating factor neutralization inhibited DC and T-cell expansion within
      pericardial AT, and translated into reduced bone marrow granulopoiesis and
      cardiac neutrophil infiltration 3 days after MI. The relevance of the pericardial
      AT in mediating all these effects was confirmed by removal of pericardial AT and
      ex vivo coculture with pericardial AT and granulocyte progenitors. Finally,
      enhanced fibrosis and worsened ejection fraction in CB2-/- mice were limited by
      pericardial AT removal. CONCLUSIONS: Our findings unveil a new mechanism by which
      the pericardial AT coordinates immune cell activation, granulopoiesis, and
      outcome after MI.

PMID- 29167228
TI  - Contribution of Impaired Parasympathetic Activity to Right Ventricular
      Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.
AB  - BACKGROUND: The beneficial effects of parasympathetic stimulation have been
      reported in left heart failure, but whether it would be beneficial for pulmonary
      arterial hypertension (PAH) remains to be explored. Here, we investigated the
      relationship between parasympathetic activity and right ventricular (RV) function
      in patients with PAH, and the potential therapeutic effects of pyridostigmine
      (PYR), an oral drug stimulating the parasympathetic activity through
      acetylcholinesterase inhibition, in experimental pulmonary hypertension (PH).
      METHODS: Heart rate recovery after a maximal cardiopulmonary exercise test was
      used as a surrogate for parasympathetic activity. RV ejection fraction was
      assessed in 112 patients with PAH. Expression of nicotinic (alpha-7 nicotinic
      acetylcholine receptor) and muscarinic (muscarinic acetylcholine type 2 receptor)
      receptors, and acetylcholinesterase activity were evaluated in RV (n=11) and
      lungs (n=7) from patients with PAH undergoing heart/lung transplantation and
      compared with tissue obtained from controls. In addition, we investigated the
      effects of PYR (40 mg/kg per day) in experimental PH. PH was induced in male rats
      by SU5416 (25 mg/kg subcutaneously) injection followed by 4 weeks of hypoxia. In
      a subgroup, sympathetic/parasympathetic modulation was assessed by power spectral
      analysis. At week 6, PH status was confirmed by echocardiography, and rats were
      randomly assigned to vehicle or treatment (both n=12). At the end of the study,
      echocardiography was repeated, with additional RV pressure-volume measurements,
      along with lung, RV histological, and protein analyses. RESULTS: Patients with
      PAH with lower RV ejection fraction (<41%) had a significantly reduced heart rate
      recovery in comparison with patients with higher RV ejection fraction. In PAH RV
      samples, alpha-7 nicotinic acetylcholine receptor was increased and
      acetylcholinesterase activity was reduced versus controls. No difference in
      muscarinic acetylcholine type 2 receptor expression was observed. Chronic PYR
      treatment in PH rats normalized the cardiovascular autonomic function,
      demonstrated by an increase in parasympathetic activity and baroreflex
      sensitivity. PYR improved survival, increased RV contractility, and reduced RV
      stiffness, RV hypertrophy, RV fibrosis, RV inflammation, and RV alpha-7 nicotinic
      acetylcholine receptor and muscarinic acetylcholine type 2 receptor expression,
      as well. Furthermore, PYR reduced pulmonary vascular resistance, RV afterload,
      and pulmonary vascular remodeling, which was associated with reduced local and
      systemic inflammation. CONCLUSIONS: RV dysfunction is associated with reduced
      systemic parasympathetic activity in patients with PAH, with an inadequate
      adaptive response of the cholinergic system in the RV. Enhancing parasympathetic
      activity by PYR improved survival, RV function, and pulmonary vascular remodeling
      in experimental PH.

PMID- 29167229
TI  - Embryonic Lethality and Host Immunity of RelA-Deficient Mice Are Mediated by Both
      Apoptosis and Necroptosis.
AB  - In mammalian cells, signaling pathways triggered by TNF can be switched from NF
      kappaB activation to apoptosis and/or necroptosis. The in vivo mechanisms
      underlying the mutual regulation of these three signaling pathways are poorly
      understood. In this article, we report that the embryonic lethality of RelA
      deficient mice is partially prevented by the deletion of Rip3 or Mlkl, but it is
      fully rescued by the combined ablation of Fadd and Rip3 or Mlkl or by blocking
      RIP1 kinase activity (RIP1K45A). RelA-/-Fadd-/-Rip3-/- triple-knockout (TKO) and
      RelA-/-Rip1K45A/K45A mice displayed bacterial pneumonia leading to death ~2 wk
      after birth. Moreover, RelA-/-Rip1K45A/K45A mice, but not TKO mice, developed
      severe inflammation associated with inflammatory skin lesion. Antibiotic
      treatment improved bacterial pneumonia, extended the lifespan of TKO and RelA-/
      Rip1K45A/K45A mice, and alleviated skin inflammation in RelA-/-Rip1K45A/K45A
      mice. These results show the mechanisms underlying the in vivo mutual regulation
      between NF-kappaB activation and the cell death pathway and provide new insights
      into this interplay in embryonic development and host immune homeostasis.

PMID- 29167231
TI  - Reticulon-1 and Reduced Migration toward Chemoattractants by Macrophages
      Differentiated from the Bone Marrow of Ultraviolet-Irradiated and Ultraviolet
      Chimeric Mice.
AB  - The ability of macrophages to respond to chemoattractants and inflammatory
      signals is important for their migration to sites of inflammation and immune
      activity and for host responses to infection. Macrophages differentiated from the
      bone marrow (BM) of UV-irradiated mice, even after activation with LPS, migrated
      inefficiently toward CSF-1 and CCL2. When BM cells were harvested from UV
      irradiated mice and transplanted into naive mice, the recipient mice (UV
      chimeric) had reduced accumulation of elicited monocytes/macrophages in the
      peritoneal cavity in response to inflammatory thioglycollate or alum. Macrophages
      differentiating from the BM of UV-chimeric mice also had an inherent reduced
      ability to migrate toward chemoattractants in vitro, even after LPS activation.
      Microarray analysis identified reduced reticulon-1 mRNA expressed in macrophages
      differentiated from the BM of UV-chimeric mice. By using an anti-reticulon-1 Ab,
      a role for reticulon-1 in macrophage migration toward both CSF-1 and CCL2 was
      confirmed. Reticulon-1 subcellular localization to the periphery after exposure
      to CSF-1 for 2.5 min was shown by immunofluorescence microscopy. The proposal
      that reduced reticulon-1 is responsible for the poor inherent ability of
      macrophages to respond to chemokine gradients was supported by Western blotting.
      In summary, skin exposure to erythemal UV radiation can modulate macrophage
      progenitors in the BM such that their differentiated progeny respond
      inefficiently to signals to accumulate at sites of inflammation and immunity.

PMID- 29167230
TI  - Absence of CD59 in Guinea Pigs: Analysis of the Cavia porcellus Genome Suggests
      the Evolution of a CD59 Pseudogene.
AB  - CD59 is a membrane-bound regulatory protein that inhibits the assembly of the
      terminal membrane attack complex (C5b-9) of complement. From its original
      discovery in humans almost 30 years ago, CD59 has been characterized in a variety
      of species, from primates to early vertebrates, such as teleost fish. CD59 is
      ubiquitous in mammals; however, we have described circumstantial evidence
      suggesting that guinea pigs (Cavia porcellus) lack CD59, at least on
      erythrocytes. In this study, we have used a combination of phylogenetic analyses
      with syntenic alignment of mammalian CD59 genes to identify the only span of
      genomic DNA in C. porcellus that is homologous to a portion of mammalian CD59 and
      show that this segment of DNA is not transcribed. We describe a pseudogene
      sharing homology to exons 2 through 5 of human CD59 present in the C. porcellus
      genome. This pseudogene was flanked by C. porcellus homologs of two genes, FBXO3
      and ORF91, a relationship and orientation that were consistent with other known
      mammalian CD59 genes. Analysis using RNA sequencing confirmed that this segment
      of chromosomal DNA was not transcribed. We conclude that guinea pigs lack an
      intact gene encoding CD59; to our knowledge, this is the first report of a
      mammalian species that does not express a functional CD59. The pseudogene we
      describe is likely the product of a genomic deletion event during its
      evolutionary divergence from other members of the rodent order.

PMID- 29167232
TI  - Identification of IFN-gamma and IL-27 as Critical Regulators of Respiratory
      Syncytial Virus-Induced Exacerbation of Allergic Airways Disease in a Mouse
      Model.
AB  - Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which
      leads to worsening of clinical symptoms and may result in a sustained decline in
      lung function. Exacerbations are the main cause of morbidity and mortality
      associated with asthma, and significantly contribute to asthma-associated
      healthcare costs. Although glucocorticoids are used to manage exacerbations, some
      patients respond to them poorly. The underlying mechanisms associated with
      steroid-resistant exacerbations remain largely unknown. We have previously
      established a mouse model of RSV-induced exacerbation of allergic airways
      disease, which mimics hallmark clinical features of asthma. In this study, we
      have identified key roles for macrophage IFN-gamma and IL-27 in the regulation of
      RSV-induced exacerbation of allergic airways disease. Production of IFN-gamma and
      IL-27 was steroid-resistant, and neutralization of IFN-gamma or IL-27
      significantly suppressed RSV-induced steroid-resistant airway hyperresponsiveness
      and airway inflammation. We have previously implicated activation of pulmonary
      macrophage by TNF-alpha and/or MCP-1 in the mechanisms of RSV-induced
      exacerbation. Stimulation of pulmonary macrophages with TNF-alpha and/or MCP-1
      induced expression of both IFN-gamma and IL-27. Our findings highlight critical
      roles for IFN-gamma and IL-27, downstream of TNF-alpha and MCP-1, in the
      mechanism of RSV-induced exacerbation. Thus, targeting the pathways that these
      factors activate may be a potential therapeutic approach for virus-induced asthma
      exacerbations.

PMID- 29167234
TI  - Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or
      Foxp3-Independent Dominant Immune Tolerance.
AB  - It has been shown that dominant tolerance, namely in transplantation, requires
      Foxp3+ regulatory T cells. Although most tolerance-inducing regimens rely on
      regulatory T cells, we found that induction of tolerance to proteins in aluminum
      hydroxide can be achieved in Foxp3-deficient mice using nondepleting anti-CD4
      Abs. This type of tolerance is Ag specific, and tolerant mice retain immune
      competence to respond to unrelated Ags. We demonstrated with chicken OVA-specific
      TCR-transgenic mice that the same tolerizing protocol (CD4 blockade) and the same
      target Ag (OVA) achieves Foxp3-dependent transplantation tolerance to OVA
      expressing skin grafts, but Foxp3-independent tolerance when the Ag is provided
      as OVA-aluminum hydroxide. In the latter case, we found that tolerance induction
      triggered recessive mechanisms leading to elimination of effector cells and,
      simultaneously, a dominant mechanism associated with the emergence of an anergic
      and regulatory CTLA-4+IL-2lowFoxp3- T cell population, where the tolerance state
      is IL-10 dependent. Such Foxp3-independent mechanisms can improve the efficacy of
      tolerance-inducing protocols.

PMID- 29167233
TI  - Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory
      Cytokines by Monocytes in Aging.
AB  - Dysregulated inflammation is implicated in the pathobiology of aging, yet
      platelet-leukocyte interactions and downstream cytokine synthesis in aging
      remains poorly understood. Platelets and monocytes were isolated from healthy
      younger (age <45, n = 37) and older (age >=65, n = 30) adults and incubated
      together under autologous and nonautologous conditions. Synthesis of inflammatory
      cytokines by monocytes, alone or in the presence of platelets, was examined. Next
      generation RNA-sequencing allowed for unbiased profiling of the platelet
      transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not
      differ between older and younger adults. However, in the presence of autologous
      platelets, monocytes from older adults synthesized greater IL-8 (41 +/- 5 versus
      9 +/- 2 ng/ml, p < 0.0001) and MCP-1 (867 +/- 150 versus 216 +/- 36 ng/ml, p <
      0.0001) than younger adults. Platelets from older adults were sufficient for
      upregulating the synthesis of inflammatory cytokines by monocytes. Using RNA
      sequencing of platelets followed by validation via RT-PCR and immunoblot, we
      discovered that granzyme A (GrmA), a serine protease not previously identified in
      human platelets, increases with aging (~9-fold versus younger adults, p < 0.05)
      and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1.
      Inhibiting GrmA reduced excessive IL-8 and MCP-1 synthesis in aging to levels
      similar to younger adults. In summary, human aging is associated with changes in
      the platelet transcriptome and proteome. GrmA is present and bioactive in human
      platelets, is higher in older adults, and controls the synthesis of inflammatory
      cytokines by monocytes. Alterations in the platelet molecular signature and
      signaling to monocytes may contribute to dysregulated inflammatory syndromes in
      older adults.

PMID- 29167235
TI  - Cortisol limits selected actions of synthetic glucocorticoids in the airway
      epithelium.
AB  - Cortisol, a physiologic glucocorticoid (GC), is essential for growth and
      differentiation of the airway epithelium. Epithelial function influences
      inflammation in chronic respiratory diseases. Synthetic GCs, including inhaled
      corticosteroids, exert anti-inflammatory effects in airway epithelium by
      transactivation of genes and by inhibition of proinflammatory cytokine release.
      We examined the effect of cortisol on the actions of synthetic GCs in the airway
      epithelium, demonstrating that cortisol acts like a partial agonist at the GC
      receptor (GR), limiting GC-induced GR-dependent transcription in the BEAS-2B
      human bronchial epithelial cell line. Cortisol also limited the inhibition of
      granulocyte macrophage colony-stimulating factor release by synthetic GCs in TNF
      alpha-activated BEAS-2B cells. The relevance of these findings is supported by
      observations on tracheal epithelium obtained from mice treated for 5 d with
      systemic GC, showing limitations in selected GC effects, including inhibition of
      IL-6. Moreover, gene transactivation by synthetic GCs was compromised by standard
      air-liquid interface (ALI) growth medium cortisol concentration (1.4 MUM) in the
      ALI-differentiated organotypic culture of primary human airway epithelial cells.
      These findings suggest that endogenous corticosteroids may limit certain actions
      of synthetic pharmacological GCs and contribute to GC insensitivity, particularly
      when corticosteroid levels are elevated by stress.-Prodanovic, D., Keenan, C. R.,
      Langenbach, S., Li, M., Chen, Q., Lew, M. J., Stewart, A. G. Cortisol limits
      selected actions of synthetic glucocorticoids in the airway epithelium.

PMID- 29167236
TI  - P-body-induced inactivation of let-7a miRNP prevents the death of growth factor
      deprived neuronal cells.
AB  - RNA processing bodies (P-bodies) are cytoplasmic RNA granules in eukaryotic cells
      that regulate gene expression by executing the translation suppression and
      degradation of mRNAs that are targeted to these bodies. P-bodies can also serve
      as storage sites for translationally repressed mRNAs both in mammalian cells and
      yeast cells. In this report, a unique role of mammalian P-bodies is documented.
      Depletion of P-body components dedifferentiate nerve growth factor-treated PC12
      cells, whereas ectopic expression of P-body components induces the neuronal
      differentiation of precursor cells. Trophic factor withdrawal from differentiated
      cells induces a decrease in cellular P-body size and numbers that are coupled
      with dedifferentiation and cell death. Here, we report how the expression of P
      body proteins-by ensuring the phosphorylation of argonaute protein 2 and the
      subsequent inactivation let-7a miRNPs-prevents the apoptotic death of growth
      factor-depleted neuronal cells.-Patranabis, S., Bhattacharyya, S. N. P-body
      induced inactivation of let-7a miRNP prevents the death of growth factor-deprived
      neuronal cells.

PMID- 29167237
TI  - Changes in the dispensing of opioid medications in Canada following the
      introduction of a tamper-deterrent formulation of long-acting oxycodone: a time
      series analysis.
AB  - BACKGROUND: In February 2012, a reformulated tamper-deterrent form of long-acting
      oxycodone, OxyNeo, was introduced in Canada. We investigated the impact of the
      introduction of OxyNeo on patterns of opioid prescribing. METHODS: We conducted
      population-based, cross-sectional analyses of opioid dispensing in Canada between
      2008 and 2016. We estimated monthly community pharmacy dispensing of oral
      formulations of codeine, morphine, hydromorphone and oxycodone, and a transdermal
      formulation of fentanyl, and converted quantities to milligrams of morphine
      equivalents (MMEs) per 1000 population. We used time series analysis to evaluate
      the effect of the introduction of OxyNeo on these trends. RESULTS: National
      dispensing of long-acting opioids fell by 14.9% between February 2012 and April
      2016, from 36 098 MMEs to 30 716 MMEs per 1000 population (p < 0.01). This effect
      varied across Canada and was largest in Ontario (reduction of 22.8%) (p = 0.01)
      and British Columbia (reduction of 30.0%) (p = 0.01). The national rate of
      oxycodone dispensing fell by 46.4% after the introduction of OxyNeo (p < 0.001);
      this was partially offset by an increase of 47.8% in hydromorphone dispensing (p
      < 0.001). Although dispensing of immediate-release opioids was a substantial
      contributor to overall population opioid exposure across Canada, it was
      unaffected by the introduction of OxyNeo (p > 0.05 in all provinces).
      INTERPRETATION: The findings suggest that the introduction of a tamper-deterrent
      formulation of long-acting oxycodone in Canada, against a background of changing
      public drug benefits, was associated with sustained changes in selection of long
      acting opioids but only small changes in the quantity of long-acting opioids
      dispensed. This illustrates the limited effect a tamper-deterrent formulation and
      associated coverage policy can have when other, non-tamper-deterrent alternatives
      are readily available.

PMID- 29167238
TI  - Complete Genome Sequences of Seven Vibrio cholerae Phages Isolated in China.
AB  - The complete genome sequences of seven closely related Vibrio cholerae phages
      isolated from environmental sites in southeastern China are reported here. Phages
      QH, CJY, H1, H2, H3, J2, and J3 are members of the Podoviridae family and are
      highly similar to the previously sequenced Vibrio phages VP2, VP5, and phiVC8.

PMID- 29167239
TI  - Complete Genome Sequence of the Novel Bacteriophage pSco-10 Infecting
      Staphylococcus cohnii.
AB  - Herein, we report the complete genome sequence of the Staphylococcus Myoviridae
      phage pSco-10 infecting Staphylococcus cohnii The phage pSco-10 was isolated from
      duck feces collected from four farms in South Korea. The current report provides
      valuable information for genomic study of phages.

PMID- 29167240
TI  - Complete Chloroplast Genome Sequence of Chenopodium album from Northeastern
      India.
AB  - Chenopodium album belongs to the complex genus Chenopodium of the family
      Amaranthaceae. It is an economically and medicinally important plant. We report
      here the first complete chloroplast genome sequence of C. album from northeastern
      India. This study shall add extensive information on the evolutionary
      relationships of the genus Chenopodium.

PMID- 29167241
TI  - Complete Chloroplast Genome Sequence of Cane Needle Grass, Nassella hyalina
      (Poaceae: Stipeae).
AB  - Nassella hyalina (cane needle grass) is on the Alert List for Environmental Weeds
      in Australia. We present here the first complete chloroplast sequence of N.
      hyalina reconstructed from Illumina whole-genome sequencing. The complete
      chloroplast sequence is 137,606 bp in size and has a gene content and structure
      similar to those of other published chloroplast genomes of Stipeae.

PMID- 29167242
TI  - Complete Nucleotide Sequence of Australian Tomato spotted wilt virus Isolate TSWV
      QLD2.
AB  - The complete nucleotide (nt) sequence of an Australian isolate of Tomato spotted
      wilt virus was determined by deep RNA sequencing and deep small RNA sequencing.
      The tripartite genome consists of an 8,914-nt L segment, a 4,851-nt M segment,
      and a 2,987-nt S segment.

PMID- 29167243
TI  - Draft Genome Sequences of Aggregatibacter actinomycetemcomitans Strains 310a and
      310b.
AB  - We report the draft genome sequences of Aggregatibacter actinomycetemcomitans
      strains 310a (310-TR) and 310b (310-OS). Strain 310a is a clinical isolate with a
      rough phenotype. Strain 310b is a laboratory-adapted isolate derived from the
      passage of 310a and displays a smooth phenotype.

PMID- 29167244
TI  - Draft Genome Sequence of the Planktic Cyanobacterium Tychonema bourrellyi,
      Isolated from Alpine Lentic Freshwater.
AB  - We describe here the draft genome sequence of the cyanobacterium Tychonema
      bourrellyi, assembled from a metagenome of a nonaxenic culture. The strain
      (FEM_GT703) was isolated from a freshwater sample taken from Lake Garda, Italy.
      The draft genome sequence represents the first assembled T. bourrellyi strain.

PMID- 29167245
TI  - Complete Genome Sequence of Enterococcus thailandicus Strain a523 Isolated from
      Urban Raw Sewage.
AB  - We report here the first complete circularly closed genome sequence of
      Enterococcus thailandicus strain a523 isolated from raw urban sewage. This genome
      contains 2,646,250 bp with a G+C content of 36.8%, 2,499 genes, 2,370 protein
      coding sequences, 6 rRNA operons, 65 tRNAs, and 6 clustered regularly interspaced
      short palindromic repeat arrays.

PMID- 29167246
TI  - Complete 4.55-Megabase-Pair Genome of "Candidatus Fluviicola riflensis," Curated
      from Short-Read Metagenomic Sequences.
AB  - We report the 4.55-Mbp genome of "Candidatus Fluviicola riflensis"
      (Bacteroidetes) that was manually curated to completion from Illumina data. "Ca
      Fluviicola riflensis" is a facultative anaerobe. Its ability to grow over a range
      of O2 levels may favor its proliferation in an aquifer adjacent to the Colorado
      River in the United States.

PMID- 29167247
TI  - Draft Genome Sequence of Burkholderia puraquae Type Strain CAMPA 1040, Isolated
      from Hospital Settings in Cordoba, Argentina.
AB  - We report here the draft genome sequence of Burkholderia puraquae type strain
      CAMPA 1040, a member of the Burkholderia cepacia complex. This strain, isolated
      from a hemodialysis water reservoir, harbors several stress tolerance genes, such
      as the systems for low oxygen survival, for copper tolerance, and for osmotic
      stress resistance.

PMID- 29167248
TI  - Complete Genome Sequence of a Novel Variant of Wenzhou Mammarenavirus.
AB  - Wenzhou mammarenavirus (WENV) is a novel species of Arenavirus that was first
      detected in China. We report here a novel WENV variant (WENV G107) from liver
      samples of Rattus norvegicus that shares 84.7% to 86.8% (large [L] segment) and
      84.2% to 87.8% (small [S] segment) nucleotide sequence identity with its closest
      relative. The genomic characteristics were analyzed based on the whole genome of
      WENV G107.

PMID- 29167249
TI  - Draft Genome Sequence of Tepidibacter mesophilus Strain JCM 16806T Isolated from
      Soil Polluted by Crude Oil in China.
AB  - Here, we report the draft genome sequence of Tepidibacter mesophilus strain JCM
      16806T, which was isolated from an oil field. It is composed of 3,310,272 bp and
      contains 3,160 protein-coding genes, 8 5S rRNAs, 3 16S rRNAs, and 69 tRNAs.

PMID- 29167250
TI  - Draft Genome Sequence of Mycobacterium sp. Strain shizuoka-1, a Novel
      Mycobacterium Isolated from Groundwater of a Bathing Facility in Shizuoka, Japan.
AB  - Mycobacterium sp. strain shizuoka-1 is a rapidly growing scotochromogenic
      mycobacterium and was isolated from well water for a bathing facility in Shizuoka
      Prefecture in Japan. Here, we report the draft sequence of its genome, comprising
      a 6.5-Mb chromosome. This mycobacterium has 83.1% identity with Mycobacterium
      rhodesiae, a human pathogen.

PMID- 29167251
TI  - Complete Genome Sequence of Human Coronavirus Strain 229E Isolated from Plasma
      Collected from a Haitian Child in 2016.
AB  - Human coronavirus strain 229E (HCoV-229E) and human alphaherpesvirus 1 were
      isolated from the plasma of a Haitian child in 2016 with suspected arbovirus
      diseases. To our knowledge, this is the first description of HCoV-229E in human
      plasma, which is the focus of this article.

PMID- 29167252
TI  - Metagenome of the Siberian Underground Water Reservoir.
AB  - We report on the metagenome of a deep subsurface aquifer in the Tomsk region of
      Russia, sampled via an oil exploration borehole drilled to a depth of 2.8 km.
      Methanogenic archaea were present in the water along with members of various
      bacterial phyla, including Firmicutes, Chloroflexi, Bacteroidetes,
      Ignavibacteriae, and uncultured candidate divisions.

PMID- 29167253
TI  - Draft Genome Sequence of Sphingobium fuliginis OMI, a Bacterium That Degrades
      Alkylphenols and Bisphenols.
AB  - Sphingobium fuliginis OMI is a bacterium that can degrade a variety of
      recalcitrant alkylphenols and bisphenols. This study reports the draft genome
      sequence of S. fuliginis OMI.

PMID- 29167254
TI  - Draft Genome Sequence of the Arsenic-Resistant Bacterium Brevundimonas
      denitrificans TAR-002T.
AB  - We report the 3.2-Mb draft genome sequence of Brevundimonas denitrificans strain
      TAR-002T, isolated from deep-sea floor sediment. The draft genome sequence of
      strain TAR-002T consists of 3,231,216 bp in 44 contigs, with a G+C content of
      68.47%, 3,866 potential coding sequences (CDSs), 3 rRNAs, and 45 tRNAs.

PMID- 29167255
TI  - Complete Genome Sequences of Two Plant-Associated Pseudomonas putida Isolates
      with Increased Heavy-Metal Tolerance.
AB  - We report here the complete genome sequences of two Pseudomonas putida isolates
      recovered from surface-sterilized roots of Sida hermaphrodita The two isolates
      were characterized by an increased tolerance to zinc, cadmium, and lead.
      Furthermore, the strains showed typical plant growth-promoting properties, such
      as the production of indole acetic acid, cellulolytic enzymes, and siderophores.

PMID- 29167256
TI  - First Complete Genome Sequences of Anopheles A Virus of the Genus
      Orthobunyavirus.
AB  - Here, we report the first complete genome sequence of Anopheles A virus (ANAV)
      that was isolated from Colombia in 1940, and we include the first description of
      the medium and large segments. The ANAV medium and large segments share the
      highest identity with serogroup member Lukuni virus, which causes human
      infection.

PMID- 29167257
TI  - Draft Genome Sequence of Pseudomonas fluorescens Strain TR3, a Potential
      Biocontrol Agent against the Rice Blast Fungus Magnaporthe oryzae.
AB  - We present the draft genome sequence of the potential biocontrol agent
      Pseudomonas fluorescens TR3, which was isolated from rice leaves infected with
      Magnaporthe oryzae in a greenhouse. The genome of TR3 was assembled into 26
      scaffolds (~6 Mbp) and includes genes potentially involved in bacterial
      interactions with fungi.

PMID- 29167258
TI  - Draft Genome Sequence of an Indian Marine Cyanobacterial Strain with Fast Growth
      and High Polyglucan Content.
AB  - Marine cyanobacteria play an important role in global carbon cycling and are a
      potential source of polyglucans for biotechnological purposes. This report
      provides the draft sequence of an Indian marine cyanobacterium, Synechococcus
      elongatus BDU 130192, which shows fast growth and high polyglucan content. The
      genome sequence will help in understanding the unique properties of this
      organism.

PMID- 29167259
TI  - Whole-Genome Sequencing of Lactobacillus salivarius Strains BCRC 14759 and BCRC
      12574.
AB  - Lactobacillus salivarius BCRC 14759 has been identified as a high
      exopolysaccharide-producing strain with potential as a probiotic or fermented
      dairy product. Here, we report the genome sequences of L. salivarius BCRC 14759
      and the comparable strain BCRC 12574, isolated from human saliva. The PacBio RSII
      sequencing platform was used to obtain high-quality assemblies for
      characterization of this probiotic candidate.

PMID- 29167260
TI  - Genomic Characterization of the First Equine-Like G3P[8] Rotavirus Strain
      Detected in the United States.
AB  - We report here the full coding region sequences for all 11 segments of the first
      equine-like G3P[8] rotavirus strain detected in the United States, strain
      RVA/Human-wt/USA/3000390639/2015/G3P[8]. The full genotype constellation of this
      strain is G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2.

PMID- 29167261
TI  - The Whole-Genome Sequence of Bacillus velezensis Strain SB1216 Isolated from the
      Great Salt Plains of Oklahoma Reveals the Presence of a Novel Extracellular RNase
      with Antitumor Activity.
AB  - The whole-genome sequence of Bacillus velezensis strain SB1216, isolated from the
      Great Salt Plains of Oklahoma, showed the presence of a 3,814,720-bp circular
      chromosome and no plasmids. The presence of a novel 870-bp extracellular RNase
      gene is predicted to be responsible for this strain's antitumor activity.

PMID- 29167262
TI  - Complete Genome Sequence of the Predatory Bacterium Ensifer adhaerens Casida A.
AB  - We report here the complete genome sequence of the facultative predatory
      bacterium Ensifer adhaerens strain Casida A. The genome was assembled into three
      circular contigs, with a main chromosome as well as two large secondary
      replicons, that totaled 7,267,502 bp with 6,641 predicted open reading frames.

PMID- 29167263
TI  - Complete Genome Sequences of Campylobacter jejuni Strains Isolated from Retail
      Chicken and Chicken Gizzards.
AB  - Genome sequences of Campylobacter jejuni FJ3124 and ZP3204 isolated from retail
      chicken gizzards and Campylobacter jejuni TS1218 isolated from retail chicken
      showed the presence of 1,694,324-, 1,763,161-, and 1,762,596-bp circular
      chromosomes, respectively. Campylobacter jejuni ZP3204 and TS1218 harbored large
      tetracycline resistance plasmids with type IV secretion systems.

PMID- 29167264
TI  - Complete Genome Sequences of Two Strains of the Meat Spoilage Bacterium
      Brochothrix thermosphacta Isolated from Ground Chicken.
AB  - Brochothrix thermosphacta is an important meat spoilage bacterium. Here we report
      the genome sequences of two strains of B. thermosphacta isolated from ground
      chicken. The genome sequences were determined using long-read PacBio single
      molecule real-time (SMRT) technology and are the first complete genome sequences
      reported for B. thermosphacta.

PMID- 29167265
TI  - Complete Circularized Genome Sequences of Four Strains of Elizabethkingia
      anophelis, Including Two Novel Strains Isolated from Wild-Caught Anopheles
      sinensis.
AB  - We provide complete circularized genome sequences of two mosquito-derived
      Elizabethkingia anophelis strains with draft sequences currently in the public
      domain (R26 and Ag1), and two novel E. anophelis strains derived from a different
      mosquito species, Anopheles sinensis (AR4-6 and AR6-8). The genetic similarity of
      all four mosquito-derived strains is remarkable.

PMID- 29167266
TI  - Complete Genome Sequences of Plasmid-Bearing Multidrug-Resistant Campylobacter
      jejuni and Campylobacter coli Strains with Type VI Secretion Systems, Isolated
      from Retail Turkey and Pork.
AB  - We report the complete genome sequences of multidrug-resistant Campylobacter
      jejuni and Campylobacter coli isolated from retail turkey and pork, respectively.
      The chromosomes of these two isolates contained type VI secretion system genes.
      The two isolates also harbored large plasmids with antimicrobial resistance genes
      possibly contributing to their multidrug resistance.

PMID- 29167267
TI  - Complete Genome Sequence of Collinsella aerofaciens Isolated from the Gut of a
      Healthy Indian Subject.
AB  - Collinsella aerofaciens, a rod-shaped nonmotile obligate anaerobe, is the most
      abundant actinobacterium in the gastrointestinal tract of healthy humans. An
      altered abundance of C. aerofaciens may be linked with several health disorders,
      including irritable bowel syndrome. In the present study, we report the complete
      genome sequence of C. aerofaciens strain indica.

PMID- 29167268
TI  - The shaker-1 mouse myosin VIIa deafness mutation results in a severely reduced
      rate of the ATP hydrolysis step.
AB  - Mutations in the MYO7A gene, encoding the motor protein myosin VIIa, can cause
      Usher 1B, a deafness/blindness syndrome in humans, and the shaker-1 phenotype,
      characterized by deafness, head tossing, and circling behavior, in mice. Myosin
      VIIa is responsible for tension bearing and the transduction mechanism in the
      stereocilia and for melanosome transport in the retina, in line with the
      phenotypic outcomes observed in mice. However, the effect of the shaker-1
      mutation, a R502P amino acid substitution, on the motor function is unclear. To
      explore this question, we determined the kinetic properties and the effect on the
      filopodial tip localization of the recombinant mouse myosin VIIa-5IQ-SAH R502P
      (myoVIIa-sh1) construct. Interestingly, although residue 502 is localized to a
      region thought to be involved in interacting with actin, the kinetic parameters
      for actin binding changed only slightly for the mutant construct. However, the
      rate constant for ATP hydrolysis (k+H + k-H) was reduced by ~200-fold from 12 s-1
      to 0.05 s-1, making the hydrolysis step the rate-limiting step of the ATPase
      cycle in the presence and absence of actin. Given that wild-type mouse myosin
      VIIa is a slow, high-duty ratio, monomeric motor, this altered hydrolysis rate
      would reduce activity to extremely low levels. Indeed, the translocation to the
      filopodial tips was hampered by the diminished motor function of a dimeric
      construct of the shaker-1 mutant. We conclude that the diminished motor activity
      of this mutant is most likely responsible for impaired hearing in the shaker-1
      mice.

PMID- 29167269
TI  - Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53
      binding protein 1 (53BP1) focus formation.
AB  - Cells have evolved sophisticated mechanisms to maintain genomic integrity in
      response to DNA damage. Ionizing radiation (IR)-induced DNA damage results in the
      formation of IR-induced foci (iRIF) in the nucleus. The iRIF formation is part of
      the DNA damage response (DDR), which is an essential signaling cascade that must
      be strictly regulated because either the loss of or an augmented DDR leads to
      loss of genome integrity. Accordingly, negative regulation of the DDR is as
      critical as its activation. In this study, we have identified ring finger protein
      126 (RNF126) as a negative regulator of the DDR from a screen of iRIF containing
      53BP1. RNF126 overexpression abolishes not only the formation of 53BP1 iRIF but
      also of RNF168, FK2, RAP80, and BRCA1. However, the iRIF formation of gammaH2AX,
      MDC1, and RNF8 is maintained, indicating that RNF126 acts between RNF8 and RNF168
      during the DDR. In addition, RNF126 overexpression consistently results in the
      loss of RNF168-mediated H2A monoubiquitination at lysine 13/15 and inhibition of
      the non-homologous end joining capability. Taken together, our findings reveal
      that RNF126 is a novel factor involved in the negative regulation of DDR, which
      is important for sustaining genomic integrity.

PMID- 29167270
TI  - UbiA prenyltransferase domain-containing protein-1 modulates HMG-CoA reductase
      degradation to coordinate synthesis of sterol and nonsterol isoprenoids.
AB  - UBIAD1 (UbiA prenyltransferase domain-containing protein-1) utilizes
      geranylgeranyl pyrophosphate (GGpp) to synthesize vitamin K2 We previously
      reported that sterols stimulate binding of UBIAD1 to endoplasmic reticulum (ER)
      localized 3-hydroxy-3-methylglutaryl (HMG) CoA reductase. UBIAD1 binding inhibits
      sterol-accelerated, ER-associated degradation (ERAD) of reductase, one of several
      mechanisms for feedback control of this rate-limiting enzyme in the branched
      pathway that produces cholesterol and nonsterol isoprenoids such as GGpp.
      Accumulation of GGpp in ER membranes triggers release of UBIAD1 from reductase,
      permitting its maximal ERAD and ER-to-Golgi transport of UBIAD1. Mutant UBIAD1
      variants associated with Schnyder corneal dystrophy (SCD), a human disorder
      characterized by corneal accumulation of cholesterol, resist GGpp-induced release
      from reductase and remain sequestered in the ER to block reductase ERAD. Using
      lines of genetically manipulated cells, we now examine consequences of UBIAD1
      deficiency and SCD-associated UBIAD1 on reductase ERAD and cholesterol synthesis.
      Our results indicated that reductase becomes destabilized in the absence of
      UBIAD1, resulting in reduced cholesterol synthesis and intracellular
      accumulation. In contrast, an SCD-associated UBIAD1 variant inhibited reductase
      ERAD, thereby stabilizing the enzyme and contributing to enhanced synthesis and
      intracellular accumulation of cholesterol. Finally, we present evidence that GGpp
      regulated, ER-to-Golgi transport enables UBIAD1 to modulate reductase ERAD such
      that synthesis of nonsterol isoprenoids is maintained in sterol-replete cells.
      These findings further establish UBIAD1 as a central player in the reductase ERAD
      pathway and regulation of isoprenoid synthesis. They also indicate that UBIAD1
      mediated inhibition of reductase ERAD underlies cholesterol accumulation
      associated with SCD.

PMID- 29167271
TI  - Reference Assembly and Annotation of the Pyrenophora teres f. teres Isolate 0-1.
AB  - Pyrenophora teres f. teres, the causal agent of net form net blotch (NFNB) of
      barley, is a destructive pathogen in barley-growing regions throughout the world.
      Typical yield losses due to NFNB range from 10 to 40%; however, complete loss has
      been observed on highly susceptible barley lines where environmental conditions
      favor the pathogen. Currently, genomic resources for this economically important
      pathogen are limited to a fragmented draft genome assembly and annotation, with
      limited RNA support of the P. teres f. teres isolate 0-1. This research presents
      an updated 0-1 reference assembly facilitated by long-read sequencing and
      scaffolding with the assistance of genetic linkage maps. Additionally, genome
      annotation was mediated by RNAseq analysis using three infection time points and
      a pure culture sample, resulting in 11,541 high-confidence gene models. The 0-1
      genome assembly and annotation presented here now contains the majority of the
      repetitive content of the genome. Analysis of the 0-1 genome revealed classic
      characteristics of a "two-speed" genome, being compartmentalized into GC
      equilibrated and AT-rich compartments. The assembly of repetitive AT-rich regions
      will be important for future investigation of genes known as effectors, which
      often reside in close proximity to repetitive regions. These effectors are
      responsible for manipulation of the host defense during infection. This updated
      P. teres f. teres isolate 0-1 reference genome assembly and annotation provides a
      robust resource for the examination of the barley-P. teres f. teres host-pathogen
      coevolution.

PMID- 29167272
TI  - Direct Testing for Allele-Specific Expression Differences Between Conditions.
AB  - Allelic imbalance (AI) indicates the presence of functional variation in cis
      regulatory regions. Detecting cis regulatory differences using AI is widespread,
      yet there is no formal statistical methodology that tests whether AI differs
      between conditions. Here, we present a novel model and formally test differences
      in AI across conditions using Bayesian credible intervals. The approach tests AI
      by environment (G*E) interactions, and can be used to test AI between
      environments, genotypes, sex, and any other condition. We incorporate bias into
      the modeling process. Bias is allowed to vary between conditions, making the
      formulation of the model general. As gene expression affects power for detection
      of AI, and, as expression may vary between conditions, the model explicitly takes
      coverage into account. The proposed model has low type I and II error under
      several scenarios, and is robust to large differences in coverage between
      conditions. We reanalyze RNA-seq data from a Drosophila melanogaster population
      panel, with F1 genotypes, to compare levels of AI between mated and virgin female
      flies, and we show that AI * genotype interactions can also be tested. To
      demonstrate the use of the model to test genetic differences and interactions, a
      formal test between two F1s was performed, showing the expected 20% difference in
      AI. The proposed model allows a formal test of G*E and G*G, and reaffirms a
      previous finding that cis regulation is robust between environments.

PMID- 29167273
TI  - Restorer-of-Fertility Mutations Recovered in Transposon-Active Lines of S Male
      Sterile Maize.
AB  - Mitochondria execute key pathways of central metabolism and serve as cellular
      sensing and signaling entities, functions that depend upon interactions between
      mitochondrial and nuclear genetic systems. This is exemplified in cytoplasmic
      male sterility type S (CMS-S) of Zea mays, where novel mitochondrial open reading
      frames are associated with a pollen collapse phenotype, but nuclear restorer-of
      fertility (restorer) mutations rescue pollen function. To better understand these
      genetic interactions, we screened Activator-Dissociation (Ac-Ds),
      Enhancer/Suppressor-mutator (En/Spm), and Mutator (Mu) transposon-active CMS-S
      stocks to recover new restorer mutants. The frequency of restorer mutations
      increased in transposon-active stocks compared to transposon-inactive stocks, but
      most mutants recovered from Ac-Ds and En/Spm stocks were unstable, reverting upon
      backcrossing to CMS-S inbred lines. However, 10 independent restorer mutations
      recovered from CMS-S Mu transposon stocks were stable upon backcrossing. Many
      restorer mutations condition seed-lethal phenotypes that provide a convenient
      test for allelism. Eight such mutants recovered in this study included one pair
      of allelic mutations that were also allelic to the previously described rfl2-1
      mutant. Targeted analysis of mitochondrial proteins by immunoblot identified two
      features that consistently distinguished restored CMS-S pollen from comparably
      staged, normal-cytoplasm, nonmutant pollen: increased abundance of nuclear
      encoded alternative oxidase relative to mitochondria-encoded cytochrome oxidase
      and decreased abundance of mitochondria-encoded ATP synthase subunit 1 compared
      to nuclear-encoded ATP synthase subunit 2. CMS-S restorer mutants thus revealed a
      metabolic plasticity in maize pollen, and further study of these mutants will
      provide new insights into mitochondrial functions that are critical to pollen and
      seed development.

PMID- 29167274
TI  - Distinct Cellular Mechanisms Underlie Smooth Muscle Turnover in Vascular
      Development and Repair.
AB  - RATIONALE: Vascular smooth muscle turnover has important implications for blood
      vessel repair and for the development of cardiovascular diseases, yet lack of
      specific transgenic animal models has prevented it's in vivo analysis. OBJECTIVE:
      The objective of this study was to characterize the dynamics and mechanisms of
      vascular smooth muscle turnover from the earliest stages of embryonic development
      to arterial repair in the adult. METHODS AND RESULTS: We show that CD146 is
      transiently expressed in vascular smooth muscle development. By using CRISPR-Cas9
      genome editing and in vitro smooth muscle differentiation assay, we demonstrate
      that CD146 regulates the balance between proliferation and differentiation. We
      developed a triple-transgenic mouse model to map the fate of NG2+CD146+ immature
      smooth muscle cells. A series of pulse-chase experiments revealed that the origin
      of aortic vascular smooth muscle cells can be traced back to progenitor cells
      that reside in the wall of the dorsal aorta of the embryo at E10.5. A distinct
      population of CD146+ smooth muscle progenitor cells emerges during embryonic
      development and is maintained postnatally at arterial branch sites. To
      characterize the contribution of different cell types to arterial repair, we used
      2 injury models. In limited wire-induced injury response, existing smooth muscle
      cells are the primary contributors to neointima formation. In contrast,
      microanastomosis leads to early smooth muscle death and subsequent colonization
      of the vascular wall by proliferative adventitial cells that contribute to the
      repair. CONCLUSIONS: Extensive proliferation of immature smooth muscle cells in
      the primitive embryonic dorsal aorta establishes the long-lived lineages of
      smooth muscle cells that make up the wall of the adult aorta. A discrete
      population of smooth muscle cells forms in the embryo and is postnatally
      sustained at arterial branch sites. In response to arterial injuries, existing
      smooth muscle cells give rise to neointima, but on extensive damage, they are
      replaced by adventitial cells.

PMID- 29167276
TI  - PTEN Loss Promotes Intratumoral Androgen Synthesis and Tumor Microenvironment
      Remodeling via Aberrant Activation of RUNX2 in Castration-Resistant Prostate
      Cancer.
AB  - Purpose: Intratumoral androgen synthesis (IAS) is a key mechanism promoting
      androgen receptor (AR) reactivation and antiandrogen resistance in castration
      resistant prostate cancer (CRPC). However, signaling pathways driving aberrant
      IAS remain poorly understood.Experimental Design: The effect of components of the
      AKT-RUNX2-osteocalcin (OCN)-GPRC6A-CREB signaling axis on expression of
      steroidogenesis genes CYP11A1 and CYP17A1 and testosterone level were examined in
      PTEN-null human prostate cancer cell lines. Pten knockout mice were used to
      examine the effect of Runx2 heterozygous deletion or abiraterone acetate (ABA), a
      prodrug of the CYP17A1 inhibitor abiraterone on Cyp11a1 and Cyp17a1 expression,
      testosterone level and tumor microenvironment (TME) remodeling in vivoResults: We
      uncovered that activation of the AKT-RUNX2-OCN-GPRC6A-CREB signaling axis induced
      expression of CYP11A1 and CYP17A1 and testosterone production in PTEN-null
      prostate cancer cell lines in culture. Deletion of Runx2 in Pten homozygous
      knockout prostate tumors decreased Cyp11a1 and Cyp17a1 expression, testosterone
      level, and tumor growth in castrated mice. ABA treatment also inhibited
      testosterone synthesis and alleviated Pten loss-induced tumorigenesis in vivoPten
      deletion induced TME remodeling, but Runx2 heterozygous deletion or ABA treatment
      reversed the effect of Pten loss by decreasing expression of the collagenase
      Mmp9.Conclusions: Abnormal RUNX2 activation plays a pivotal role in PTEN loss
      induced IAS and TME remodeling, suggesting that the identified signaling cascade
      represents a viable target for effective treatment of PTEN-null prostate cancer,
      including CRPC. Clin Cancer Res; 24(4); 834-46. (c)2017 AACR.

PMID- 29167275
TI  - Residual Convolutional Neural Network for the Determination of IDH Status in Low-
      and High-Grade Gliomas from MR Imaging.
AB  - Purpose: Isocitrate dehydrogenase (IDH) mutations in glioma patients confer
      longer survival and may guide treatment decision making. We aimed to predict the
      IDH status of gliomas from MR imaging by applying a residual convolutional neural
      network to preoperative radiographic data.Experimental Design: Preoperative
      imaging was acquired for 201 patients from the Hospital of University of
      Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138
      patients from The Cancer Imaging Archive (TCIA) and divided into training,
      validation, and testing sets. We trained a residual convolutional neural network
      for each MR sequence (FLAIR, T2, T1 precontrast, and T1 postcontrast) and built a
      predictive model from the outputs. To increase the size of the training set and
      prevent overfitting, we augmented the training set images by introducing random
      rotations, translations, flips, shearing, and zooming.Results: With our neural
      network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0%
      (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing
      sets, respectively. When age at diagnosis was incorporated into the model, the
      training, validation, and testing accuracies increased to 87.3% (AUC = 0.93),
      87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively.Conclusions: We
      developed a deep learning technique to noninvasively predict IDH genotype in
      grade II-IV glioma using conventional MR imaging using a multi-institutional data
      set. Clin Cancer Res; 24(5); 1073-81. (c)2017 AACR.

PMID- 29167277
TI  - Aging-Related Disease Risks among Young Thyroid Cancer Survivors.
AB  - Background: Thyroid cancer is the most rapidly increasing cancer in the United
      States, affects a young population, has high survival, and is one of the most
      common cancers in people under age 40. The aim of this study was to examine the
      risks of aging-related diseases in a statewide sample of thyroid cancer survivors
      who were diagnosed <40 years compared with those diagnosed >=40 and a cancer-free
      sample.Methods: Thyroid cancer survivors diagnosed 1997 to 2012 were matched to
      up to 5 cancer-free individuals on birth year, sex, birth state, using the
      statewide Utah Population Database. Medical records were used to identify disease
      diagnoses stratified over three time periods: 1 to 5, >5 to 10, and 10+ years
      after cancer diagnosis. Cox proportional hazards models were used to estimate
      hazard ratios with adjustment on matching factors, race, body mass index, and
      Charlson Comorbidity Index.Results: There were 3,706 thyroid cancer survivors and
      15,587 matched cancer-free individuals (1,365 cases diagnosed <40 years old).
      Both age groups had increased risks for multiple circulatory health conditions 1
      to 5 years after cancer diagnosis compared with cancer-free individuals.
      Survivors <40 had a higher risk of hypertension, cardiomyopathy, and nutritional
      deficiencies.Conclusions: Increased risks for diseases associated with aging were
      observed for both age groups, with younger thyroid cancer survivors having higher
      risks for select diseases.Impact: As thyroid cancer survivors in this study were
      found to have increased risks for aging-related diseases, future studies are
      needed to assess what can be done to reduce the increased risks of these long
      term health effects. Cancer Epidemiol Biomarkers Prev; 26(12); 1695-704. (c)2017
      AACR.

PMID- 29167280
TI  - Knotty Problems during Mitosis: Mechanistic Insight into the Processing of
      Ultrafine DNA Bridges in Anaphase.
AB  - To survive and proliferate, cells have to faithfully segregate their newly
      replicated genomic DNA to the two daughter cells. However, the sister chromatids
      of mitotic chromosomes are frequently interlinked by so-called ultrafine DNA
      bridges (UFBs) that are visible in the anaphase of mitosis. UFBs can only be
      detected by the proteins bound to them and not by staining with conventional DNA
      dyes. These DNA bridges are presumed to represent entangled sister chromatids and
      hence pose a threat to faithful segregation. A failure to accurately unlink UFB
      DNA results in chromosome segregation errors and binucleation. This, in turn,
      compromises genome integrity, which is a hallmark of cancer. UFBs are actively
      removed during anaphase, and most known UFB-associated proteins are enzymes
      involved in DNA repair in interphase. However, little is known about the mitotic
      activities of these enzymes or the exact DNA structures present on UFBs. We focus
      on the biology of UFBs, with special emphasis on their underlying DNA structure
      and the decatenation machineries that process UFBs.

PMID- 29167278
TI  - Blood Pressure Status in Adult Survivors of Childhood Cancer: A Report from the
      St. Jude Lifetime Cohort Study.
AB  - Background: Hypertension potentiates cardiovascular risk in survivors of
      childhood cancer previously exposed to cardiotoxic therapies, so it is important
      to determine the prevalence and risk factors for hypertensive blood pressure in
      this high-risk group.Methods: Participants included 3,016 adult 10-year survivors
      of childhood cancer who had resting blood pressure measurements performed at St.
      Jude Children's Research Hospital (Memphis, TN). We characterized the blood
      pressure status of participants, calculated standardized prevalence ratios based
      on U.S. population rates, and examined demographic and treatment factors
      associated with hypertensive blood pressure using logistic regression.Results:
      The age-specific cumulative prevalence of hypertension in survivors increased
      sharply with age, exceeding 70% by age 50, and was substantially higher in all
      diagnosis groups than expected on the basis of age-, sex-, race/ethnicity-, and
      BMI-specific population rates. Specific cancer treatments were not significantly
      associated with hypertension, with the exception of nephrectomy (OR, 1.68; 95%
      confidence interval, 1.11-2.53). Previously undiagnosed hypertensive blood
      pressure was identified in 8% of survivors, and uncontrolled hypertension in 22%
      of those with a previous hypertension diagnosis. In a subset (n = 1,185) with
      longitudinal blood pressure measurements (mean interval, 3.6 years), 5% and 21%
      of participants with previously normal blood pressure developed hypertensive and
      prehypertensive blood pressure, respectively.Conclusions: Survivors of childhood
      cancer have a higher prevalence of hypertension compared with the general
      population, and many have uncontrolled hypertension that may exacerbate treatment
      related cardiovascular risks.Impact: Our results suggest enhanced clinical
      attention to blood pressure status is warranted in all survivors, regardless of
      diagnosis or cancer treatment. Cancer Epidemiol Biomarkers Prev; 26(12); 1705-13.
      (c)2017 AACR.

PMID- 29167281
TI  - Polytene Chromosome Structure and Somatic Genome Instability.
AB  - Polytene chromosomes have for 80 years provided the highest resolution view of
      interphase genome structure in an animal cell nucleus. These chromosomes
      represent the normal genomic state of nearly all Drosophila larval and many adult
      cells, and a better understanding of their striking banded structure has been
      sought for decades. A more recently appreciated characteristic of Drosophila
      polytene cells is somatic genome instability caused by unfinished replication
      (UR). Repair of stalled forks generates enough deletions in polytene salivary
      gland cells to alter 10%-90% of the DNA strands within more than 100 UR regions
      comprising 20% of the euchromatic genome. We accurately map UR regions and show
      that most approximate large polytene bands, indicating that replication forks
      frequently stall near band boundaries in late S phase. Chromosome conformation
      capture has recently identified dense topologically associated domains (TADs) in
      many genomes and most UR bands are similar or slightly smaller than a cognate
      Drosophila TAD. We argue that bands serve the evolutionarily ancient function of
      coordinating genome replication with local gene activity. We also discuss the
      relatively recent evolution of polyteny and somatic instability in Diptera and
      propose that these processes helped propel the amazing success of two-winged
      flies in becoming the most ecologically diverse insect group, with 200 times the
      number of species as mammals.

PMID- 29167279
TI  - Height, Obesity, and the Risk of TMPRSS2:ERG-Defined Prostate Cancer.
AB  - Background: The largest molecular subtype of primary prostate cancer is defined
      by the TMPRSS2:ERG gene fusion. Few studies, however, have investigated etiologic
      differences by TMPRSS2:ERG status. Because the fusion is hormone-regulated and a
      man's hormonal milieu varies by height and obesity status, we hypothesized that
      both may be differentially associated with risk of TMPRSS2:ERG-defined
      disease.Methods: Our study included 49,372 men from the prospective Health
      Professionals Follow-up Study. Participants reported height and weight at
      baseline in 1986 and updated weight biennially thereafter through 2009. Tumor ERG
      protein expression (a TMPRSS2:ERG marker) was immunohistochemically assessed. We
      used multivariable competing risks models to calculate HRs and 95% confidence
      intervals (CIs) for the risk of ERG-positive and ERG-negative prostate
      cancer.Results: During 23 years of follow-up, we identified 5,847 incident
      prostate cancers, among which 913 were ERG-assayed. Taller height was associated
      with an increased risk of ERG-positive disease only [per 5 inches HR 1.24; 95%
      confidence interval (CI), 1.03-1.50; Pheterogeneity = 0.07]. Higher body mass
      index (BMI) at baseline (per 5 kg/m2 HR 0.75; 95% CI, 0.61-0.91; Pheterogeneity =
      0.02) and updated BMI over time (per 5 kg/m2 HR 0.86; 95% CI, 0.74-1.00;
      Pheterogeneity = 0.07) were associated with a reduced risk of ERG-positive
      disease only.Conclusions: Our results indicate that anthropometrics may be
      uniquely associated with TMPRSS2:ERG-positive prostate cancer; taller height may
      be associated with greater risk, whereas obesity may be associated with lower
      risk.Impact: Our study provides strong rationale for further investigations of
      other prostate cancer risk factors that may be distinctly associated with
      subtypes. Cancer Epidemiol Biomarkers Prev; 27(2); 193-200. (c)2017 AACR.

PMID- 29167282
TI  - Structure and Epigenetic Regulation of Chromatin Fibers.
AB  - In eukaryotes, genomic DNA is hierarchically packaged by histones into chromatin
      on several levels to fit inside the nucleus. As a central-level structure between
      nucleosomal arrays and higher-order chromatin organizations, the 30-nm chromatin
      fiber and its dynamics play a crucial role in gene regulation. However, despite
      considerable efforts over the past three decades, the fundamental structure and
      its dynamic regulation of chromatin fibers still remain as a big challenge in
      molecular biology. Here, we mainly summarize the most recent progress in
      elucidating the structure of the 30-nm chromatin fiber in vitro and epigenetic
      regulation of chromatin fibers by chromatin factors, particularly histone
      variants. In addition, we also discuss recent studies in unraveling the three
      dimensional organization of chromatin fibers in situ by genomic approaches and
      electron microscopy.

PMID- 29167283
TI  - RotoStep: A Chromosome Dynamics Simulator Reveals Mechanisms of Loop Extrusion.
AB  - ChromoShake is a three-dimensional simulator designed to explore the range of
      configurational states a chromosome can adopt based on thermodynamic fluctuations
      of the polymer chain. Here, we refine ChromoShake to generate dynamic simulations
      of a DNA-based motor protein such as condensin walking along the chromatin
      substrate. We model walking as a rotation of DNA-binding heat-repeat proteins
      around one another. The simulation is applied to several configurations of DNA to
      reveal the consequences of mechanical stepping on taut chromatin under tension
      versus loop extrusion on single-tethered, floppy chromatin substrates. These
      simulations provide testable hypotheses for condensin and other DNA-based motors
      functioning along interphase chromosomes. Our model reveals a novel mechanism for
      condensin enrichment in the pericentromeric region of mitotic chromosomes.
      Increased condensin dwell time at centromeres results in a high density of
      pericentric loops that in turn provide substrate for additional condensin.

PMID- 29167284
TI  - Molecular Structures of Yeast Kinetochore Subcomplexes and Their Roles in
      Chromosome Segregation.
AB  - Kinetochore molecular architecture exemplifies "form follows function." The
      simplifications that generated the one-chromosome:one-microtubule linkage in
      point-centromere yeast have enabled strategies for systematic structural analysis
      and high-resolution visualization of many kinetochore components, leading to
      specific proposals for molecular mechanisms. We describe here some structural
      features that allow a kinetochore to remain attached to the end of a
      depolymerizing microtubule (MT) and some characteristics of the connections
      between substructures that permit very sensitive regulation by differential
      kinase activities. We emphasize in particular the importance of flexible
      connections between rod-like structural members and the integration of these
      members into a compliant cage-like assembly anchored on the MT by a sliding
      molecular ring.

PMID- 29167285
TI  - Macrophagic "Crown-like Structures" Are Associated with an Increased Risk of
      Breast Cancer in Benign Breast Disease.
AB  - In breast adipose tissue, macrophages that encircle damaged adipocytes form
      "crown-like structures of breast" (CLS-B). Although CLS-B have been associated
      with breast cancer, their role in benign breast disease (BBD) and early
      carcinogenesis is not understood. We evaluated breast biopsies from three age
      matched groups (n = 86 each, mean age 55 years), including normal tissue donors
      of the Susan G. Komen for the Cure Tissue Bank (KTB), and subjects in the Mayo
      Clinic Benign Breast Disease Cohort who developed cancer (BBD cases) or did not
      develop cancer (BBD controls, median follow-up 14 years). Biopsies were
      classified into histologic categories, and CD68-immunostained tissue sections
      were evaluated for the frequency and density of CLS-B. Our data demonstrate that
      CLS-B are associated with BBD: CLS-B-positive samples were significantly less
      frequent among KTB biopsies (3/86, 3.5%) than BBD controls (16/86 = 18.6%, P =
      0.01) and BBD cases (21/86 = 24%, P = 0.002). CLS-B were strongly associated with
      body mass index (BMI); BMI < 25: 7% CLS-B positive, BMI 25-29: 13%, and BMI >=
      30: 29% (P = 0.0005). Among BBD biopsies, a high CLS-B count [>5 CLS-B/sample:
      10.5% (BBD cases) vs 4.7% (BBD controls), P = 0.007] conferred a breast cancer OR
      of 6.8 (95% CI, 1.4-32.4), P = 0.02, after adjusting for adipose tissue area
      (cm2), histologic impression, and BMI. As high CLS-B densities are independently
      associated with an increased breast cancer risk, they may be a promising
      histologic marker of breast cancer risk in BBD. Cancer Prev Res; 11(2); 113-9.
      (c)2017 AACR.

PMID- 29167286
TI  - A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic
      dyskinesia and benign familial infantile seizures.
AB  - Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder
      characterized by recurrent attacks of dyskinetic movements without alteration of
      consciousness that are often triggered by the initiation of voluntary movements.
      Whole-exome sequencing has revealed a cluster of pathogenic variants in PRRT2
      (proline-rich transmembrane protein), a gene with a function in synaptic
      regulation that remains poorly understood. Here, we report the discovery of a
      novel PRRT2 pathogenic variant inherited in an autosomal dominant pattern in a
      family with PKD and benign familial infantile seizures (BFIS). After targeted
      Sanger sequencing did not identify the presence of previously described PRRT2
      pathogenic variants, we carried out whole-exome sequencing in the proband and her
      affected paternal grandfather. This led to the discovery of a novel PRRT2
      variant, NM_001256442:exon3:c.C959T/NP_660282.2:p.A320V, altering an
      evolutionarily conserved alanine at the amino acid position 320 located in the M2
      transmembrane region. Sanger sequencing further confirmed the presence of this
      variant in four affected family members (paternal grandfather, father, brother,
      and proband) and its absence in two unaffected ones (paternal grandmother and
      mother). This newly found variant further reinforces the importance of PRRT2 in
      PKD, BFIS, and possibly other movement disorders. Future functional studies using
      animal models and human pluripotent stem cell models will provide new insights
      into the role of PRRT2 and the significance of this variant in regulating neural
      development and/or function.

PMID- 29167287
TI  - U.S. High-Level Isolation Unit Clinical Laboratory Capabilities Update.
AB  - In late 2014, 56 hospitals in the United States were designated by state and
      federal public health authorities as specially designed high-level isolation
      units (HLIUs) equipped with advanced infrastructure, laboratory capabilities, and
      trained staff to care for patients with highly hazardous communicable diseases
      (HHCDs), such as Ebola virus disease. This survey describes the clinical
      laboratory support capabilities of U.S. HLIUs, including the specific test menus
      that HLIUs have identified to safely manage HHCD patients and the locations where
      such testing would be performed. In spring 2016, a survey was electronically
      distributed, as a fillable pdf file, to the 56 U.S. HLIUs. Site representatives
      completed the surveys, and data were coded and analyzed in an electronic
      spreadsheet, using descriptive statistics. Thirty-six HLIUs (64%) responded, and
      33 completed the laboratory capabilities section. Thirty-one HLIUs (94%) had
      performed risk analyses for all laboratory procedures and equipment. Twenty-nine
      (88%) had decontamination procedures specified for all laboratory equipment used
      for patients with suspected or confirmed HHCDs. On-site laboratories in 27 HLIUs
      (81%) had the capacity to inventory and to securely store HHCD patient specimens.
      Ten HLIUs (31%) had at least one test they would conduct within the patient
      isolation room. The high-risk nature of HHCDs and the occupational exposures that
      may occur in clinical laboratories demand advanced preparation and risk
      assessment of work practices, laboratory equipment, and instrumentation by HLIU
      laboratories. Although risk analyses of clinical laboratory testing and equipment
      that HLIUs have conducted have likely focused on those for Ebola virus, HLIUs
      must be prepared to revise their current procedures for other HHCDs.

PMID- 29167288
TI  - A Predominant Variable-Number Tandem-Repeat Cluster of Mycobacterium tuberculosis
      Isolates among Asylum Seekers in the Netherlands and Denmark, Deciphered by Whole
      Genome Sequencing.
AB  - In many countries, Mycobacterium tuberculosis isolates are routinely subjected to
      variable-number tandem-repeat (VNTR) typing to investigate M. tuberculosis
      transmission. Unexpectedly, cross-border clusters were identified among African
      refugees in the Netherlands and Denmark, although transmission in those countries
      was unlikely. Whole-genome sequencing (WGS) was applied to analyze transmission
      in depth and to assess the precision of VNTR typing. WGS was applied to 40 M.
      tuberculosis isolates from refugees in the Netherlands and Denmark (most of whom
      were from the Horn of Africa) that shared the exact same VNTR profile. Cluster
      investigations were undertaken to identify in-country epidemiological links.
      Combining WGS results for the isolates (all members of the central Asian strain
      [CAS]/Delhi genotype), from both European countries, an average genetic distance
      of 80 single-nucleotide polymorphisms (SNPs) (maximum, 153 SNPs) was observed.
      The few pairs of isolates with confirmed epidemiological links, except for one
      pair, had a maximum distance of 12 SNPs. WGS divided this refugee cluster into
      several subclusters of patients from the same country of origin. Although the M.
      tuberculosis cases, mainly originating from African countries, shared the exact
      same VNTR profile, most were clearly distinguished by WGS. The average genetic
      distance in this specific VNTR cluster was 2 times greater than that in other
      VNTR clusters. Thus, identical VNTR profiles did not represent recent direct M.
      tuberculosis transmission for this group of patients. It appears that either
      these strains from Africa are extremely conserved genetically or there is ongoing
      transmission of this genotype among refugees on their long migration routes from
      Africa to Europe.

PMID- 29167289
TI  - Evaluation of the Copan ESwab Transport System for Viability of Pathogenic Fungi
      by Use of a Modification of Clinical and Laboratory Standards Institute Document
      M40-A2.
AB  - The Copan ESwab system was evaluated for its ability to maintain the viability of
      pathogenic fungi. Tests followed the Clinical and Laboratory Standards Institute
      (CLSI) document M40-A2 roll-plate method at room and refrigerator temperatures. A
      system was devised for standardizing homogeneous inoculum suspensions of
      variously sized conidia and sporangiospores of filamentous fungi. A total of 19
      clinical and reference strains were standardized to a 0.5 McFarland turbidity
      standard with a simple photometer. Corresponding optical densities were measured
      with a spectrophotometer. Colony counts equal to or greater than those seen at
      time zero were obtained for the entire test panel. Results indicate that the
      Copan ESwab system effectively maintains prevalent opportunistic fungal organisms
      for at least 48 h.

PMID- 29167290
TI  - Evaluation of Whole-Genome Sequencing for Mycobacterial Species Identification
      and Drug Susceptibility Testing in a Clinical Setting: a Large-Scale Prospective
      Assessment of Performance against Line Probe Assays and Phenotyping.
AB  - Use of whole-genome sequencing (WGS) for routine mycobacterial species
      identification and drug susceptibility testing (DST) is becoming a reality. We
      compared the performances of WGS and standard laboratory workflows prospectively,
      by parallel processing at a major mycobacterial reference service over the course
      of 1 year, for species identification, first-line Mycobacterium tuberculosis
      resistance prediction, and turnaround time. Among 2,039 isolates with line probe
      assay results for species identification, 74 (3.6%) failed sequencing or WGS
      species identification. Excluding these isolates, clinically important species
      were identified for 1,902 isolates, of which 1,825 (96.0%) were identified as the
      same species by WGS and the line probe assay. A total of 2,157 line probe test
      results for detection of resistance to the first-line drugs isoniazid and
      rifampin were available for 728 M. tuberculosis complex isolates. Excluding 216
      (10.0%) cases where there were insufficient sequencing data for WGS to make a
      prediction, overall concordance was 99.3% (95% confidence interval [CI], 98.9 to
      99.6%), sensitivity was 97.6% (91.7 to 99.7%), and specificity was 99.5% (99.0 to
      99.7%). A total of 2,982 phenotypic DST results were available for 777 M.
      tuberculosis complex isolates. Of these, 356 (11.9%) had no WGS comparator due to
      insufficient sequencing data, and in 154 (5.2%) cases the WGS prediction was
      indeterminate due to discovery of novel, previously uncharacterized mutations.
      Excluding these data, overall concordance was 99.2% (98.7 to 99.5%), sensitivity
      was 94.2% (88.4 to 97.6%), and specificity was 99.4% (99.0 to 99.7%). Median
      processing times for the routine laboratory tests versus WGS were similar
      overall, i.e., 20 days (interquartile range [IQR], 15 to 31 days) and 21 days (15
      to 29 days), respectively (P = 0.41). In conclusion, WGS predicts species and
      drug susceptibility with great accuracy, but work is needed to increase the
      proportion of predictions made.

PMID- 29167291
TI  - Candida auris: an Emerging Fungal Pathogen.
AB  - Candida auris has emerged globally as a multidrug-resistant health care
      associated fungal pathogen. Recent reports highlight ongoing challenges due to
      organism misidentification, high rates of antifungal drug resistance, and
      significant patient mortality. The predilection for transmission within and
      between health care facilities possibly promoted by virulence factors that
      facilitate skin colonization and environmental persistence is unique among
      Candida species. This minireview details the global emergence of C. auris and
      discusses issues relevant to clinical microbiology laboratories, hospital
      infection control, and antimicrobial stewardship efforts.

PMID- 29167292
TI  - Clinical Evaluation of the Cepheid Xpert TV Assay for Detection of Trichomonas
      vaginalis with Prospectively Collected Specimens from Men and Women.
AB  - Trichomoniasis is the most prevalent curable sexually transmitted disease (STD).
      It has been associated with preterm birth and the acquisition and transmission of
      HIV. Recently, nucleic acid amplification tests (NAAT) have been FDA cleared in
      the United States for detection of Trichomonas vaginalis in specimens from both
      women and men. This study reports the results of a multicenter study recently
      conducted using the Xpert TV (T. vaginalis) assay to test specimens from both men
      and women. On-demand results were available in as little as 40 min for positive
      specimens. A total of 1,867 women and 4,791 men were eligible for inclusion in
      the analysis. In women, the performance of the Xpert TV assay was compared to the
      patient infected status (PIS) derived from the results of InPouch TV broth
      culture and Aptima NAAT for T. vaginalis The diagnostic sensitivities and
      specificities of the Xpert TV assay for the combined female specimens (urine
      samples, self-collected vaginal swabs, and endocervical swabs) ranged from 99.5
      to 100% and 99.4 to 99.9%, respectively. For male urine samples, the diagnostic
      sensitivity and specificity were 97.2% and 99.9%, respectively, compared to PIS
      results derived from the results of broth culture for T. vaginalis and
      bidirectional gene sequencing of amplicons. Excellent performance characteristics
      were seen using both female and male specimens. The ease of using the Xpert TV
      assay should result in opportunities for enhanced screening for T. vaginalis in
      both men and women and, hopefully, improved control of this infection.

PMID- 29167293
TI  - Perioperative Antibiotic Prophylaxis Has No Effect on Time to Positivity and
      Proportion of Positive Samples: a Cohort Study of 64 Cutibacterium acnes Bone and
      Joint Infections.
AB  - If a bone or joint infection is suspected, perioperative antibiotic prophylaxis
      is frequently withheld until intraoperative microbiological sampling has been
      performed. This practice builds upon the hypothesis that perioperative
      antibiotics could render culture results negative and thus impede tailored
      antibiotic treatment of infections. We aimed to assess the influence of
      antibiotic prophylaxis within 30 to 60 min before surgery on time to positivity
      of microbiological samples and on proportion of positive samples in Cutibacterium
      acnes bone and joint infections. Patients with at least one sample positive for
      C. acnes between January 2005 and December 2015 were included and classified as
      having an "infection" if at least 2 samples were positive; otherwise they were
      considered to have a sample "contamination." Kaplan-Meier curves were used to
      illustrate time to culture positivity. We found 64 cases with a C. acnes
      infection and 46 classified as having a C. acnes contamination. Application of
      perioperative prophylaxis significantly differed between the infection and
      contamination groups (72.8% versus 55.8%; P < 0.001). Within the infection group,
      we found no difference in time to positivity between those who had or had not
      received a perioperative prophylaxis (7.07 days; 95% confidence interval [CI],
      6.4 to 7.7, versus 7.11 days; 95% CI, 6.8 to 7.5; P = 0.3). Also, there was no
      association between the proportion of sample positivity and the application of
      perioperative prophylaxis (71.6% versus 65.9%; P = 0.39). Since perioperative
      prophylaxis did not negatively influence the microbiological yield in C. acnes
      infections, antibiotic prophylaxis can be routinely given to avoid surgical site
      infections.

PMID- 29167294
TI  - Verification of Ceftazidime-Avibactam and Ceftolozane-Tazobactam Susceptibility
      Testing Methods against Carbapenem-Resistant Enterobacteriaceae and Pseudomonas
      aeruginosa.
AB  - Ceftazidime-avibactam and ceftolozane-tazobactam are newly approved agents for
      the treatment of infections caused by multidrug-resistant Gram-negative bacteria.
      Resistance to both agents has been described clinically. Susceptibility testing
      on automated systems is unavailable for either agent. Our objective was to
      compare the disk diffusion and Etest methods to standard broth microdilution
      (BMD) methods for testing ceftazidime-avibactam and ceftolozane-tazobactam
      against a diverse collection of carbapenem-resistant Enterobacteriaceae (CRE) and
      carbapenem-resistant Pseudomonas aeruginosa (CRP) isolates, respectively. Among
      74 ceftazidime-avibactam-susceptible and -resistant CRE isolates, BMD categorical
      agreement was higher with Etest (96%) than with disk diffusion (72%; P = 0.0003).
      Twenty-eight percent of ceftazidime-avibactam-susceptible CRE isolates were
      classified as resistant by disk diffusion. Results were comparable to those
      obtained with resistance defined genotypically. Among 72 ceftolozane-tazobactam
      susceptible and -resistant CRP isolates, the levels of BMD categorical agreement
      with disk diffusion and Etest were 94% and 96%, respectively; the only errors
      identified were minor. Our findings demonstrate that Etest measurements of
      ceftazidime-avibactam and ceftolozane-tazobactam susceptibility correlate closely
      with standard BMD methods, suggesting a useful role clinically. On the other
      hand, disk diffusion measurements overcalled CRE resistance to ceftazidime
      avibactam. A better understanding of ceftazidime-avibactam interpretive
      breakpoints is needed before disk diffusion is used routinely in the clinic.
      Until clinicians and microbiologists understand Etest and disk diffusion
      performance at their centers, test results should be interpreted cautiously.

PMID- 29167296
TI  - Predictors of pneumonia in lower respiratory tract infections: 3C prospective
      cough complication cohort study.
AB  - The aim was to aid diagnosis of pneumonia in those presenting with lower
      respiratory tract symptoms in routine primary care.A cohort of 28 883 adult
      patients with acute cough attributed to lower respiratory tract infections
      (LRTIs) was recruited from 5222 UK practices in 2009-13. Symptoms, signs and
      treatment were recorded at presentation and subsequent events followed-up for 30
      days by chart review. The predictive value of patient characteristics, presenting
      symptoms and clinical findings for the diagnosis of pneumonia in the first 7 days
      was established.Of the 720 out of 28 883 (2.5.%) radiographed within 1 week of
      the index consultation, 115 (16.0%; 0.40% of 28 883) were assigned a definite or
      probable pneumonia diagnosis. The significant independent predictors of
      radiograph-confirmed pneumonia were temperature >37.8 degrees C (RR 2.6; 95% CI
      1.5-4.8), crackles on auscultation (RR 1.8; 1.1-3.0), oxygen saturation <95% (RR
      1.7; 1.0-3.1) and pulse >100.min-1 (RR 1.9; 1.1-3.2). Most patients with
      pneumonia (99/115, 86.1%) exhibited at least one of these four clinical signs;
      the positive predictive value of having at least one of these signs was 20.2%
      (95% CI 17.3-23.1).In routine practice, radiograph-confirmed pneumonia as a short
      term complication of LRTI is very uncommon (one in 270). Pulse oximetry may aid
      the diagnosis of pneumonia in this setting.

PMID- 29167295
TI  - Sex-specific impact of asthma during pregnancy on infant gut microbiota.
AB  - Asthma during pregnancy is associated with retardation of fetal growth in a sex
      specific manner. Lactobacilli microbes influence infant growth. This study aimed
      to determine whether lactobacilli and other microbes are reduced in the gut of
      infants born to an asthmatic mother, and whether this differs by the sex of the
      infant.Mother-infant pairs (N=1021) from the Canadian Healthy Infant Longitudinal
      Development full-term cohort were studied. The abundance of infant faecal
      microbiota at 3-4 months, profiled by gene sequencing, was compared between both
      women with and without asthma treatment during pregnancy. Infant sex, maternal
      ethnicity, pre-pregnancy overweight and atopy status, birth mode, breastfeeding
      status and intrapartum antibiotic treatment were tested as covariates.Independent
      of birth mode and other covariates, male, Caucasian infants born to women with
      prenatal asthma harboured fewer lactobacilli in the gut at 3-4 months of age. If
      asthmatic mothers had pre-pregnancy overweight, the abundance of Lactobacillus in
      males was further reduced in the infant gut, whereas the microbiota of female
      infants was enriched with Bacteroidaceae Similar differences in infant gut
      microbial composition according to maternal prenatal asthma status were also more
      evident among women with food or environmental allergies.Gut lactobacilli were
      less abundant in male infants, but Bacteroidaceae were more abundant in female
      infants at 3-4 months of age, following maternal asthma during pregnancy.

PMID- 29167297
TI  - An official European Respiratory Society statement: pulmonary haemodynamics
      during exercise.
AB  - There is growing recognition of the clinical importance of pulmonary
      haemodynamics during exercise, but several questions remain to be elucidated. The
      goal of this statement is to assess the scientific evidence in this field in
      order to provide a basis for future recommendations.Right heart catheterisation
      is the gold standard method to assess pulmonary haemodynamics at rest and during
      exercise. Exercise echocardiography and cardiopulmonary exercise testing
      represent non-invasive tools with evolving clinical applications. The term
      "exercise pulmonary hypertension" may be the most adequate to describe an
      abnormal pulmonary haemodynamic response characterised by an excessive pulmonary
      arterial pressure (PAP) increase in relation to flow during exercise. Exercise
      pulmonary hypertension may be defined as the presence of resting mean PAP <25
      mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3
      Wood units. Exercise pulmonary hypertension represents the haemodynamic
      appearance of early pulmonary vascular disease, left heart disease, lung disease
      or a combination of these conditions. Exercise pulmonary hypertension is
      associated with the presence of a modest elevation of resting mean PAP and
      requires clinical follow-up, particularly if risk factors for pulmonary
      hypertension are present. There is a lack of robust clinical evidence on targeted
      medical therapy for exercise pulmonary hypertension.

PMID- 29167299
TI  - Correlates and assessment of excess cardiovascular risk in bronchiectasis.
AB  - Patients with bronchiectasis are at increased risk of cardiovascular disease. We
      aimed to identify factors associated with elevated cardiovascular risk in
      bronchiectasis, measured using aortic stiffness and cardiac biomarkers. In
      addition, we sought to compare these direct measures against calculated QRISK2
      scores.Aortic stiffness, cardiac biomarkers and systemic inflammation were
      measured in 101 adults with stable bronchiectasis. In addition, clinical and
      demographic data were collected to allow calculation of QRISK2 score and the
      bronchiectasis severity index (BSI) for each patient.The BSI score correlated
      with measured cardiovascular risk assessments, partly due to greater exacerbation
      frequency and lower forced expiratory volume in 1 s. Pulse-wave velocity was
      significantly higher in frequent exacerbators (>=3 events.year-1) than infrequent
      exacerbators (<3 events.year-1; 10.5 versus 9.2 m.s-1, p=0.01). In addition,
      frequent exacerbators had elevated serum C-reactive protein concentration,
      suggesting increased systemic inflammation (4.8 versus 2.2 mg.L-1, p=0.005).
      QRISK2 systematically underestimated cardiovascular risk in this population
      (median change in relative risk 1.29). Underestimation was associated with
      frequent exacerbations and male sex.Patients with bronchiectasis have greater
      cardiovascular risk than published reference populations. Excess cardiovascular
      risk is associated with exacerbation frequency and impaired lung function.
      Cardiovascular risk assessment in bronchiectasis should be individualised, as
      calculation tools are likely to underestimate the risk in this population.

PMID- 29167300
TI  - Respiratory adverse effects of opioids for breathlessness: a systematic review
      and meta-analysis.
AB  - Previous studies have shown that opioids can reduce chronic breathlessness in
      advanced disease. However, physicians remain reluctant to prescribe opioids for
      these patients, commonly due to fear of respiratory adverse effects. The aim of
      this study was to systematically review reported respiratory adverse effects of
      opioids in patients with advanced disease and chronic breathlessness.PubMed,
      Embase, the Cochrane Central Register of Controlled Trials, CINAHL,
      ClinicalTrials.gov and the reference lists of relevant systematic reviews were
      searched. Two independent researchers screened against predefined inclusion
      criteria and extracted data. Meta-analysis was conducted where possible.We
      included 63 out of 1990 articles, describing 67 studies. Meta-analysis showed an
      increase in carbon dioxide tension (0.27 kPa, 95% CI 0.08-0.45 kPa,) and no
      significant change in oxygen tension and oxygen saturation (both p>0.05).
      Nonserious respiratory depression (definition variable/not stated) was described
      in four out of 1064 patients. One cancer patient pretreated with morphine for
      pain needed temporary respiratory support following nebulised morphine for
      breathlessness (single case study).We found no evidence of significant or
      clinically relevant respiratory adverse effects of opioids for chronic
      breathlessness. Heterogeneity of design and study population, and low study
      quality are limitations. Larger studies designed to detect respiratory adverse
      effects are needed.

PMID- 29167302
TI  - Plain packaging of tobacco products in the European Union: an EU success story?

PMID- 29167301
TI  - Prevalence of persistent blood eosinophilia: relation to outcomes in patients
      with COPD.
AB  - The impact of blood eosinophilia in chronic obstructive pulmonary disease (COPD)
      remains controversial.To evaluate the prevalence and stability of a high level of
      blood eosinophils (>=300 cells.MUL-1) and its relationship to outcomes, we
      determined blood eosinophils at baseline and over 2 years in 424 COPD patients
      (forced expiratory volume in 1 s (FEV1) 60% predicted) and 67 smokers without
      COPD from the CHAIN cohort, and in 308 COPD patients (FEV1 60% predicted) in the
      BODE cohort. We related eosinophil levels to exacerbations and survival using Cox
      hazard analysis.In COPD patients, 15.8% in the CHAIN cohort and 12.3% in the BODE
      cohort had persistently elevated blood eosinophils at all three visits. A
      significant proportion (43.8%) of patients had counts that oscillated above and
      below the cut-off points, while the rest had persistent eosinophil levels <300
      cells.MUL-1 A similar eosinophil blood pattern was observed in controls.
      Exacerbation rates did not differ in patients with and without eosinophilia. All
      cause mortality was lower in patients with high eosinophils compared with those
      with values <300 cells.MUL-1 (15.8% versus 33.7%; p=0.026).In patients with COPD,
      blood eosinophils >=300 cells.MUL-1 persisting over 2 years was not a risk factor
      for COPD exacerbations. High eosinophil count was associated with better
      survival.

PMID- 29167303
TI  - Right ventricular longitudinal strain is diminished in systemic sclerosis
      compared with idiopathic pulmonary arterial hypertension.

PMID- 29167304
TI  - Pneumocystosis revealing immunodeficiency secondary to TERC mutation.

PMID- 29167305
TI  - Are we addressing relevant determinants of smoking cessation?

PMID- 29167306
TI  - Neuropsychiatric adverse drug reactions in children initiated on montelukast in
      real-life practice.

PMID- 29167307
TI  - Neuropsychiatric adverse drug reactions in children initiated on montelukast in
      real-life practice.

PMID- 29167298
TI  - Prevalence and burden of chronic bronchitis symptoms: results from the BOLD
      study.
AB  - We studied the prevalence, burden and potential risk factors for chronic
      bronchitis symptoms in the Burden of Obstructive Lung Disease
      study.Representative population-based samples of adults aged >=40 years were
      selected in participating sites. Participants completed questionnaires and
      spirometry. Chronic bronchitis symptoms were defined as chronic cough and phlegm
      on most days for >=3 months each year for >=2 years.Data from 24 855 subjects
      from 33 sites in 29 countries were analysed. There were significant differences
      in the prevalence of self-reported symptoms meeting our definition of chronic
      bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife
      (Nigeria) and Blantyre (Malawi). Older age, less education, current smoking,
      occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer
      and family history of chronic lung disease were all associated with increased
      risk of chronic bronchitis. Chronic bronchitis symptoms were associated with
      worse lung function, more dyspnoea, increased risk of respiratory exacerbations
      and reduced quality of life, independent of the presence of other lung
      diseases.The prevalence of chronic bronchitis symptoms varied widely across the
      studied sites. Chronic bronchitis symptoms were associated with significant
      burden both in individuals with chronic airflow obstruction and those with normal
      lung function.

PMID- 29167308
TI  - Peripheral eosinophil count as a biomarker for the management of COPD: not there
      yet.

PMID- 29167310
TI  - The first cell-fate decision of mouse preimplantation embryo development:
      integrating cell position and polarity.
AB  - During the first cell-fate decision of mouse preimplantation embryo development,
      a population of outer-residing polar cells is segregated from a second population
      of inner apolar cells to form two distinct cell lineages: the trophectoderm and
      the inner cell mass (ICM), respectively. Historically, two models have been
      proposed to explain how the initial differences between these two cell
      populations originate and ultimately define them as the two stated early
      blastocyst stage cell lineages. The 'positional' model proposes that cells
      acquire distinct fates based on differences in their relative position within the
      developing embryo, while the 'polarity' model proposes that the differences
      driving the lineage segregation arise as a consequence of the differential
      inheritance of factors, which exhibit polarized subcellular localizations, upon
      asymmetric cell divisions. Although these two models have traditionally been
      considered separately, a growing body of evidence, collected over recent years,
      suggests the existence of a large degree of compatibility. Accordingly, the main
      aim of this review is to summarize the major historical and more contemporarily
      identified events that define the first cell-fate decision and to place them in
      the context of both the originally proposed positional and polarity models, thus
      highlighting their functional complementarity in describing distinct aspects of
      the developmental programme underpinning the first cell-fate decision in mouse
      embryogenesis.

PMID- 29167311
TI  - The human CTF4-orthologue AND-1 interacts with DNA polymerase alpha/primase via
      its unique C-terminal HMG box.
AB  - A dynamic multi-protein assembly known as the replisome is responsible for DNA
      synthesis in eukaryotic cells. In yeast, the hub protein Ctf4 bridges DNA
      helicase and DNA polymerase and recruits factors with roles in metabolic
      processes coupled to DNA replication. An important question in DNA replication is
      the extent to which the molecular architecture of the replisome is conserved
      between yeast and higher eukaryotes. Here, we describe the biochemical basis for
      the interaction of the human CTF4-orthologue AND-1 with DNA polymerase alpha (Pol
      alpha)/primase, the replicative polymerase that initiates DNA synthesis. AND-1
      has maintained the trimeric structure of yeast Ctf4, driven by its conserved SepB
      domain. However, the primary interaction of AND-1 with Pol alpha/primase is
      mediated by its C-terminal HMG box, unique to mammalian AND-1, which binds the B
      subunit, at the same site targeted by the SV40 T-antigen for viral replication.
      In addition, we report a novel DNA-binding activity in AND-1, which might promote
      the correct positioning of Pol alpha/primase on the lagging-strand template at
      the replication fork. Our findings provide a biochemical basis for the specific
      interaction between two critical components of the human replisome, and indicate
      that important principles of replisome architecture have changed significantly in
      evolution.

PMID- 29167312
TI  - Inhibition of O-GlcNAcase Sensitizes Apoptosis and Reverses Bortezomib Resistance
      in Mantle Cell Lymphoma through Modification of Truncated Bid.
AB  - Aberrant energy metabolism represents a hallmark of cancer and contributes to
      numerous aggressive behaviors of cancer cells, including cell death and survival.
      Despite the poor prognosis of mantle cell lymphoma (MCL), due to the inevitable
      development of drug resistance, metabolic reprograming of MCL cells remains an
      unexplored area. Posttranslational modification of proteins via O-GlcNAcylation
      is an ideal sensor for nutritional changes mediated by O-GlcNAc transferase (OGT)
      and is removed by O-GlcNAcase (OGA). Using various small-molecule inhibitors of
      OGT and OGA, we found for the first time that O-GlcNAcylation potentiates MCL
      response to bortezomib. CRISPR interference of MGEA5 (encoding OGA) validated the
      apoptosis sensitization by O-GlcNAcylation and OGA inhibition. To identify the
      potential clinical candidates, we tested MCL response to drug-like OGA inhibitor,
      ketoconazole, and verified that it exerts similar sensitizing effect on
      bortezomib-induced apoptosis. Investigations into the underlying molecular
      mechanisms reveal that bortezomib and ketoconazole act in concert to cause the
      accumulation of truncated Bid (tBid). Not only does ketoconazole potentiate tBid
      induction, but also increases tBid stability through O-GlcNAcylation that
      interferes with tBid ubiquitination and proteasomal degradation. Remarkably,
      ketoconazole strongly enhances bortezomib-induced apoptosis in de novo bortezomib
      resistant MCL cells and in patient-derived primary cells with minimal cytotoxic
      effect on normal peripheral blood mononuclear cells and hepatocytes, suggesting
      its potential utility as a safe and effective adjuvant for MCL. Together, our
      findings provide novel evidence that combination of bortezomib and ketoconazole
      or other OGA inhibitors may present a promising strategy for the treatment of
      drug-resistant MCL. Mol Cancer Ther; 17(2); 484-96. (c)2017 AACR.

PMID- 29167309
TI  - Visualizing the complex functions and mechanisms of the anaphase promoting
      complex/cyclosome (APC/C).
AB  - The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3
      ubiquitin ligase that orchestrates cell cycle progression by mediating the
      degradation of important cell cycle regulators. During the two decades since its
      discovery, much has been learnt concerning its role in recognizing and
      ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms
      governing substrate specificity, the catalytic process of assembling
      polyubiquitin chains on its target proteins, and its regulation by
      phosphorylation and the spindle assembly checkpoint. The past few years have
      witnessed significant progress in understanding the quantitative mechanisms
      underlying these varied APC/C functions. This review integrates the overall
      functions and properties of the APC/C with mechanistic insights gained from
      recent cryo-electron microscopy (cryo-EM) studies of reconstituted human APC/C
      complexes.

PMID- 29167313
TI  - Mechanism-informed Repurposing of Minocycline Overcomes Resistance to
      Topoisomerase Inhibition for Peritoneal Carcinomatosis.
AB  - Mechanism-inspired drug repurposing that augments standard treatments offers a
      cost-effective and rapid route toward addressing the burgeoning problem of
      plateauing of effective therapeutics for drug-resistant micrometastases. We show
      that the antibiotic minocycline, by its ability to minimize DNA repair via
      reduced expression of tyrosyl-DNA phosphodiesterase-1 (Tdp1), removes a key
      process attenuating the efficacy of irinotecan, a frequently used
      chemotherapeutic against metastatic disease. Moreover, minocycline and irinotecan
      cooperatively mitigate each other's undesired cytokine inductions of VEGF and
      IL8, respectively, thereby reinforcing the benefits of each modality. These
      mechanistic interactions result in synergistic enhancement of irinotecan-induced
      platinum-resistant epithelial ovarian cancer cell death, reduced micrometastases
      in the omenta and mesentery by >75%, and an extended overall survival by 50% in a
      late-stage peritoneal carcinomatosis mouse model. Economic incentives and easy
      translatability make the repurposing of minocycline as a reinforcer of the
      topoisomerase class of chemotherapeutics extremely valuable and merits further
      investigations. Mol Cancer Ther; 17(2); 508-20. (c)2017 AACR.

PMID- 29167314
TI  - Wnt/beta-Catenin Pathway Activation Mediates Adaptive Resistance to BRAF
      Inhibition in Colorectal Cancer.
AB  - One of the most encouraging developments in oncology has been the success of BRAF
      inhibitors in BRAF-mutant melanoma. However, in contrast to its striking efficacy
      in BRAF-mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF
      mutant colorectal cancer. Although many studies on BRAF inhibitor resistance in
      colorectal cancer have focused on mechanisms underlying the reactivation of the
      EGFR/RAS/RAF/MEK/ERK pathway, the current study focuses on identifying novel
      adaptive signaling mechanisms, a fresh angle on colorectal cancer resistance to
      BRAF inhibition. We found that treatment with BRAF inhibitors (both current and
      next-generation BRAF inhibitors) upregulated the Wnt/beta-catenin pathway in
      BRAFV600E-mutant colorectal cancer cell lines through activating the cytoplasmic
      tyrosine kinase focal adhesion kinase (FAK). The results showed that FAK
      activation upon BRAF inhibitor treatment did not require EGFR or ERK1/2
      activation, implying that BRAF inhibitor treatment-induced hyperactivation of Wnt
      signaling is "pathway reactivation"-independent. BRAF inhibition-induced Wnt
      pathway activation was further validated in preclinical models of BRAFV600E
      mutant colorectal cancer, including cell line xenograft model and a patient
      derived xenograft model. Combined inhibition of BRAF/Wnt pathways or BRAF/FAK
      pathways exerted strong synergistic antitumor effects in cell culture model and
      mouse xenograft model. Overall, the current study has identified activation of
      the Wnt/beta-catenin pathway as a novel fundamental cause of colon cancer
      resistance to BRAF inhibition. Our results suggest that although complete
      vertical pathway blockade is pivotal for effective and durable control of BRAF
      mutant colorectal cancer, cotargeting parallel adaptive signaling-the Wnt/beta
      catenin pathway-is also essential. Mol Cancer Ther; 17(4); 806-13. (c)2017 AACR.

PMID- 29167315
TI  - A Novel YAP1 Inhibitor Targets CSC-Enriched Radiation-Resistant Cells and Exerts
      Strong Antitumor Activity in Esophageal Adenocarcinoma.
AB  - Mounting evidence suggests that the Hippo coactivator Yes-associated protein 1
      (YAP1) is a major mediator of cancer stem cell (CSC) properties, tumor
      progression, and therapy resistance as well as often a terminal node of many
      oncogenic pathways. Thus, targeting YAP1 may be a novel therapeutic strategy for
      many types of tumors with high YAP1 expression, including esophageal
      adenocarcinoma. However, effective YAP1 inhibitors are currently lacking. Here,
      we identify a small molecule (CA3) that not only has remarkable inhibitory
      activity on YAP1/Tead transcriptional activity but also demonstrates strong
      inhibitory effects on esophageal adenocarcinoma cell growth especially on YAP1
      high-expressing esophageal adenocarcinoma cells both in vitro and in vivo
      Remarkably, radiation-resistant cells acquire strong cancer stem cell (CSC)
      properties and aggressive phenotype, while CA3 can effectively suppress these
      phenotypes by inhibiting proliferation, inducing apoptosis, reducing tumor sphere
      formation, and reducing the fraction of ALDH1+ cells. Furthermore, CA3, combined
      with 5-FU, synergistically inhibits esophageal adenocarcinoma cell growth
      especially in YAP1 high esophageal adenocarcinoma cells. Taken together, these
      findings demonstrated that CA3 represents a new inhibitor of YAP1 and primarily
      targets YAP1 high and therapy-resistant esophageal adenocarcinoma cells endowed
      with CSC properties. Mol Cancer Ther; 17(2); 443-54. (c)2017 AACR.

PMID- 29167318
TI  - TRAIL reduces impaired glucose tolerance and NAFLD in the high-fat diet fed
      mouse.
AB  - Recent studies suggest that a circulating protein called TRAIL (TNF-related
      apoptosis inducing ligand) may have an important role in the treatment of type 2
      diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL
      delivery, when it is given before disease onset, slows down its development. The
      present study aimed at evaluating whether TRAIL had the potential not only to
      prevent, but also to treat type 2 diabetes. Thirty male C57BL/6J mice were
      randomized to a standard or a high-fat diet (HFD). After 4 weeks of HFD, mice
      were further randomized to receive either placebo or TRAIL, which was delivered
      weekly for 8 weeks. Body weight, food intake, fasting glucose, and insulin were
      measured at baseline and every 4 weeks. Tolerance tests were performed before
      drug randomization and at the end of the study. Tissues were collected for
      further analyses. Parallel in vitro studies were conducted on HepG2 cells and
      mouse primary hepatocytes. TRAIL significantly reduced body weight, adipocyte
      hypertrophy, free fatty acid levels, and inflammation. Moreover, it significantly
      improved impaired glucose tolerance, and ameliorated non-alcoholic fatty liver
      disease (NAFLD). TRAIL treatment reduced liver fat content by 47% in vivo as well
      as by 45% in HepG2 cells and by 39% in primary hepatocytes. This was associated
      with a significant increase in liver peroxisome proliferator-activated receptor
      (PPAR) gamma (PPARgamma) co-activator-1 alpha (PGC-1alpha) expression both in
      vivo and in vitro, pointing to a direct protective effect of TRAIL on the liver.
      The present study confirms the ability of TRAIL to significantly attenuate diet
      induced metabolic abnormalities, and it shows for the first time that TRAIL is
      effective also when administered after disease onset. In addition, our data shed
      light on TRAIL therapeutic potential not only against impaired glucose tolerance,
      but also against NAFLD.

PMID- 29167319
TI  - Granting an Extension: Phosphorylation of the Pol II CTD Regulates mRNAs Produced
      by Read-Through from Small Nuclear RNAs.

PMID- 29167317
TI  - Rodent vertical sleeve gastrectomy alters maternal immune health and
      fetoplacental development.
AB  - Bariatric surgery is increasingly employed to improve fertility and reduce
      obesity-related co-morbidities in obese women. Surgical weight loss not only
      improves the chance of conception but reduces the risk of pregnancy complications
      including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric
      procedures increase the incidence of intrauterine growth restriction (IUGR),
      fetal demise, thromboembolism, and other gestational disorders. Using our rodent
      model of vertical sleeve gastrectomy (VSG), we tested the hypothesis that VSG in
      diet-induced, obese dams would cause immune and placental structural
      abnormalities that may be responsible for fetal demise during pregnancy. VSG dams
      studied on gestational day (G) 19 had reduced circulating T-cell (CD3+ and CD8+)
      populations compared with lean or obese controls. Further, local interleukin (IL)
      1beta and IL 1 receptor antagonist (il1rn) cmRNA were increased in placenta of
      VSG dams. Placental barrier function was also affected, with increased
      transplacental permeability to small molecules, increased matrix
      metalloproteinase 9 expression, and increased apoptosis in VSG. Furthermore, we
      identified increased placental mTOR signaling that may contribute to preserving
      the body weight of the fetuses during gestation. These changes occurred in the
      absence of a macronutrient deficit or gestational hypertension in the VSG dams.
      In summary, previous VSG in dams may contribute to fetal demise by affecting
      maternal immune system activity and compromise placental integrity.

PMID- 29167316
TI  - Quantitative Phosphoproteomic Analysis Reveals Shared and Specific Targets of
      Arabidopsis Mitogen-Activated Protein Kinases (MAPKs) MPK3, MPK4, and MPK6.
AB  - In Arabidopsis, mitogen-activated protein kinases MPK3, MPK4, and MPK6 constitute
      essential relays for a variety of functions including cell division, development
      and innate immunity. Although some substrates of MPK3, MPK4 and MPK6 have been
      identified, the picture is still far from complete. To identify substrates of
      these MAPKs likely involved in cell division, growth and development we compared
      the phosphoproteomes of wild-type and mpk3, mpk4, and mpk6. To study the function
      of these MAPKs in innate immunity, we analyzed their phosphoproteomes following
      microbe-associated molecular pattern (MAMP) treatment. Partially overlapping
      substrates were retrieved for all three MAPKs, showing target specificity to one,
      two or all three MAPKs in different biological processes. More precisely, our
      results illustrate the fact that the entity to be defined as a specific or a
      shared substrate for MAPKs is not a phosphoprotein but a particular (S/T)P
      phosphorylation site in a given protein. One hundred fifty-two peptides were
      identified to be differentially phosphorylated in response to MAMP treatment
      and/or when compared between genotypes and 70 of them could be classified as
      putative MAPK targets. Biochemical analysis of a number of putative MAPK
      substrates by phosphorylation and interaction assays confirmed the global
      phosphoproteome approach. Our study also expands the set of MAPK substrates to
      involve other protein kinases, including calcium-dependent (CDPK) and sugar
      nonfermenting (SnRK) protein kinases.

PMID- 29167320
TI  - MAPKs Influence Pollen Tube Growth by Controlling the Formation of
      Phosphatidylinositol 4,5-Bisphosphate in an Apical Plasma Membrane Domain.
AB  - An apical plasma membrane domain enriched in the regulatory phospholipid
      phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] is critical for polar tip
      growth of pollen tubes. How the biosynthesis of PtdIns(4,5)P2 by
      phosphatidylinositol 4-phosphate 5-kinases (PI4P 5-kinases) is controlled by
      upstream signaling is currently unknown. The pollen-expressed PI4P 5-kinase
      PIP5K6 is required for clathrin-mediated endocytosis and polar tip growth in
      pollen tubes. Here, we identify PIP5K6 as a target of the pollen-expressed
      mitogen-activated protein kinase MPK6 and characterize the regulatory effects.
      Based on an untargeted mass spectrometry approach, phosphorylation of purified
      recombinant PIP5K6 by pollen tube extracts could be attributed to MPK6.
      Recombinant MPK6 phosphorylated residues T590 and T597 in the variable insert of
      the catalytic domain of PIP5K6, and this modification inhibited PIP5K6 activity
      in vitro. PIP5K6 interacted with MPK6 in yeast two-hybrid tests, immuno-pull-down
      assays, and by bimolecular fluorescence complementation at the apical plasma
      membrane of pollen tubes. In vivo, MPK6 expression resulted in reduced plasma
      membrane association of a fluorescent PtdIns(4,5)P2 reporter and decreased
      endocytosis without impairing membrane association of PIP5K6. Effects of PIP5K6
      expression on pollen tube growth and cell morphology were attenuated by
      coexpression of MPK6 in a phosphosite-dependent manner. Our data indicate that
      MPK6 controls PtdIns(4,5)P2 production and membrane trafficking in pollen tubes,
      possibly contributing to directional growth.

PMID- 29167322
TI  - Guarding the Gates: How PROCERA Helps Keep Tomato Plants from Wilting.

PMID- 29167321
TI  - An Automated Confocal Micro-Extensometer Enables in Vivo Quantification of
      Mechanical Properties with Cellular Resolution.
AB  - How complex developmental-genetic networks are translated into organs with
      specific 3D shapes remains an open question. This question is particularly
      challenging because the elaboration of specific shapes is in essence a question
      of mechanics. In plants, this means how the genetic circuitry affects the cell
      wall. The mechanical properties of the wall and their spatial variation are the
      key factors controlling morphogenesis in plants. However, these properties are
      difficult to measure and investigating their relation to genetic regulation is
      particularly challenging. To measure spatial variation of mechanical properties,
      one must determine the deformation of a tissue in response to a known force with
      cellular resolution. Here, we present an automated confocal micro-extensometer
      (ACME), which greatly expands the scope of existing methods for measuring
      mechanical properties. Unlike classical extensometers, ACME is mounted on a
      confocal microscope and uses confocal images to compute the deformation of the
      tissue directly from biological markers, thus providing 3D cellular scale
      information and improved accuracy. Additionally, ACME is suitable for measuring
      the mechanical responses in live tissue. As a proof of concept, we demonstrate
      that the plant hormone gibberellic acid induces a spatial gradient in mechanical
      properties along the length of the Arabidopsis thaliana hypocotyl.

PMID- 29167323
TI  - Prefrontal cortical-specific differences in behavior and synaptic plasticity
      between adolescent and adult mice.
AB  - Adolescence is a highly vulnerable period for the emergence of major
      neuropsychological disorders and is characterized by decreased cognitive control
      and increased risk-taking behavior and novelty-seeking. The prefrontal cortex
      (PFC) is involved in the cognitive control of impulsive and risky behavior.
      Although the PFC is known to reach maturation later than other cortical areas,
      little information is available regarding the functional changes from adolescence
      to adulthood in PFC, particularly compared with other primary cortical areas.
      This study aims to understand the development of PFC-mediated, compared with non
      PFC-mediated, cognitive functions. Toward this aim, we performed cognitive
      behavioral tasks in adolescent and adult mice and subsequently investigated
      synaptic plasticity in two different cortical areas. Our results showed that
      adolescent mice exhibit impaired performance in PFC-dependent cognitive tasks
      compared with adult mice, whereas their performance in non-PFC-dependent tasks is
      similar to that of adults. Furthermore, adolescent mice exhibited decreased long
      term potentiation (LTP) within upper-layer synapses of the PFC but not the barrel
      cortex. Blocking GABAA receptor function significantly augments LTP in both the
      adolescent and adult PFC. No change in intrinsic excitability of PFC pyramidal
      neurons was observed between adolescent and adult mice. Finally, increased
      expression of the NR2A subunit of the N-methyl-d-aspartate receptors is found
      only in the adult PFC, a change that could underlie the emergence of LTP. In
      conclusion, our results demonstrate physiological and behavioral changes during
      adolescence that are specific to the PFC and could underlie the reduced cognitive
      control in adolescents. NEW & NOTEWORTHY This study reports that adolescent mice
      exhibit impaired performance in cognitive functions dependent on the prefrontal
      cortex but not in cognitive functions dependent on other cortical regions. The
      current results propose reduced synaptic plasticity in the upper layers of the
      prefrontal cortex as a cellular correlate of this weakened cognitive function.
      This decreased synaptic plasticity is due to reduced N-methyl-d-aspartate
      receptor expression but not due to dampened intrinsic excitability or enhanced
      GABAergic signaling during adolescence.

PMID- 29167324
TI  - Impact of spatiotemporal calcium dynamics within presynaptic active zones on
      synaptic delay at the frog neuromuscular junction.
AB  - The spatiotemporal calcium dynamics within presynaptic neurotransmitter release
      sites (active zones, AZs) at the time of synaptic vesicle fusion is critical for
      shaping the dynamics of neurotransmitter release. Specifically, the relative
      arrangement and density of voltage-gated calcium channels (VGCCs) as well as the
      concentration of calcium buffering proteins can play a large role in the timing,
      magnitude, and plasticity of release by shaping the AZ calcium profile. However,
      a high-resolution understanding of the role of AZ structure in spatiotemporal
      calcium dynamics and how it may contribute to functional heterogeneity at an
      adult synapse is currently lacking. We demonstrate that synaptic delay varies
      considerably across, but not within, individual synapses at the frog
      neuromuscular junction (NMJ). To determine how elements of the AZ could
      contribute to this variability, we performed a parameter search using a spatially
      realistic diffusion reaction-based computational model of a frog NMJ AZ (Dittrich
      M, Pattillo JM, King JD, Cho S, Stiles JR, Meriney SD. Biophys J 104: 2751-2763,
      2013; Ma J, Kelly L, Ingram J, Price TJ, Meriney SD, Dittrich M. J Neurophysiol
      113: 71-87, 2015). We demonstrate with our model that synaptic delay is sensitive
      to significant alterations in the spatiotemporal calcium dynamics within an AZ at
      the time of release caused by manipulations of the density and organization of
      VGCCs or by the concentration of calcium buffering proteins. Furthermore, our
      data provide a framework for understanding how AZ organization and structure are
      important for understanding presynaptic function and plasticity. NEW & NOTEWORTHY
      The structure of presynaptic active zones (AZs) can play a large role in
      determining the dynamics of neurotransmitter release across many model
      preparations by influencing the spatiotemporal calcium dynamics within the AZ at
      the time of vesicle fusion. However, less is known about how different AZ
      structural schemes may influence the timing of neurotransmitter release. We
      demonstrate that variations in AZ structure create different spatiotemporal
      calcium profiles that, in turn, lead to differences in synaptic delay.

PMID- 29167325
TI  - The modulation of hippocampal theta rhythm by the vestibular system.
AB  - The vestibular system is a sensory system that has evolved over millions of years
      to detect acceleration of the head, both rotational and translational, in three
      dimensions. One of its most important functions is to stabilize gaze during
      unexpected head movement; however, it is also important in the control of posture
      and autonomic reflexes. Theta rhythm is a 3- to 12-Hz oscillating EEG signal that
      is intimately linked to self-motion and is also known to be important in learning
      and memory. Many studies over the last two decades have shown that selective
      activation of the vestibular system, using either natural rotational or
      translational stimulation, or electrical stimulation of the peripheral vestibular
      system, can induce and modulate theta activity. Furthermore, inactivation of the
      vestibular system has been shown to significantly reduce theta in freely moving
      animals, which may be linked to its impairment of place cell function as well as
      spatial learning and memory. The pathways through which vestibular information
      modulate theta rhythm remain debatable. However, vestibular responses have been
      found in the pedunculopontine tegmental nucleus (PPTg) and activation of the
      vestibular system causes an increase in acetylcholine release into the
      hippocampus, probably from the medial septum. Therefore, a pathway from the
      vestibular nucleus complex and/or cerebellum to the PPTg, supramammillary
      nucleus, posterior hypothalamic nucleus, and septum to the hippocampus is likely.
      The modulation of theta by the vestibular system may have implications for
      vestibular effects on cognitive function and the contribution of vestibular
      impairment to the risk of dementia.

PMID- 29167326
TI  - Tactile perception of the roughness of 3D-printed textures.
AB  - Surface roughness is one of the most important qualities in haptic perception.
      Roughness is a major identifier for judgments of material composition, comfort,
      and friction and is tied closely to manual dexterity. Some attention has been
      given to the study of roughness perception in the past, but it has typically
      focused on noncontrollable natural materials or on a narrow range of artificial
      materials. The advent of high-resolution three-dimensional (3D) printing
      technology provides the ability to fabricate arbitrary 3D textures with precise
      surface geometry to be used in tactile studies. We used parametric modeling and
      3D printing to manufacture a set of textured plates with defined element spacing,
      shape, and arrangement. Using active touch and two-alternative forced-choice
      protocols, we investigated the contributions of these surface parameters to
      roughness perception in human subjects. Results indicate that large spatial
      periods produce higher estimations of roughness (with Weber fraction = 0.19),
      small texture elements are perceived as rougher than large texture elements of
      the same wavelength, perceptual differences exist between textures with the same
      spacing but different arrangements, and roughness equivalencies exist between
      textures differing along different parameters. We posit that papillary ridges
      serve as tactile processing units, and neural ensembles encode the spatial
      profiles of the texture contact area to produce roughness estimates. The stimuli
      and the manufacturing process may be used in further studies of tactile roughness
      perception and in related neurophysiological applications. NEW & NOTEWORTHY
      Surface roughness is an integral quality of texture perception. We manufactured
      textures using high-resolution 3D printing, which allows precise specification of
      the surface spatial topography. In human psychophysical experiments we
      investigated the contributions of specific surface parameters to roughness
      perception. We found that textures with large spatial periods, small texture
      elements, and irregular, isotropic arrangements elicit the highest estimations of
      roughness. We propose that roughness correlates inversely with the total
      contacted surface area.

PMID- 29167327
TI  - Learning-induced modulation of the effect of endocannabinoids on inhibitory
      synaptic transmission.
AB  - are key modulators that regulate central brain functions and behaviors, including
      learning and memory. At the cellular and molecular levels, endocannabinoids are
      potent modulators of excitatory and inhibitory synaptic function. Most effects of
      cannabinoids are thought to be mediated via G protein-coupled cannabinoid
      receptors. In particular, cannabinoids released from postsynaptic neurons are
      suggested to act as retrograde messengers, activating presynaptic type-1
      cannabinoid receptors (CB1Rs), thereby inducing suppression of synaptic release.
      Another central mechanism of cannabinoid-induced action requires activation of
      astroglial CB1Rs. CB1Rs are also implicated in self-modulation of cortical
      neurons. Rats that are trained in a particularly difficult olfactory
      discrimination task show a dramatic increased ability to acquire memories of new
      odors. The memory of the acquired high-skill acquisition, termed "rule learning"
      or "learning set," lasts for many months. Using this behavioral paradigm, we show
      a novel function of action for CB1Rs, supporting long-term memory by maintaining
      persistent enhancement of inhibitory synaptic transmission. Long-lasting
      enhancement of inhibitory synaptic transmission is blocked by a CB1R inverse
      agonist. This effect is mediated by a novel purely postsynaptic mechanism,
      obtained by enhancing the single GABAA channel conductance that is PKA dependent.
      The significant role that CB1R has in maintaining learning-induced long-term
      strengthening of synaptic inhibition suggests that endocannabinoids have a key
      role in maintaining long-term memory by enhancing synaptic inhibition. NEW &
      NOTEWORTHY In this study we show a novel function and mechanism of action for
      cannabinoids in neurons, mediated by activation of type-1 cannabinoid receptors,
      supporting long-term memory by maintaining persistent enhancement of inhibitory
      synaptic transmission on excitatory neurons. This effect is mediated by a novel
      purely postsynaptic mechanism, obtained by enhancing the single GABAA channel
      conductance that is PKA dependent. Thus we report for the first time that
      endocannabinoids have a key role maintaining learning-induced synaptic
      modification.

PMID- 29167328
TI  - Perceptual decisions based on previously learned information are independent of
      dopaminergic tone.
AB  - Both cognitive and motor symptoms in people with Parkinson's disease (PD) arise
      from either too little or too much dopamine (DA). Akinesia stems from DA neuronal
      cell loss, and dyskinesia often stems from an overdose of DA medication.
      Cognitive behaviors typically associated with frontal cortical function, such as
      working memory and task switching, are also affected by too little or too much DA
      in PD. Whether motor and cognitive circuits overlap in PD is unknown. In this
      article, we show that whereas motor performance improves in people with PD when
      on dopaminergic medication compared with off medication, perceptual decision
      making based on previously learned information (priors) remains impaired whether
      on or off medications. To rule out effects of long-term DA treatment and
      dopaminergic neuronal loss such as occur in PD, we also tested a group of people
      with dopa-unresponsive focal dystonia, a disease that involves the basal ganglia,
      like PD, but has motor symptoms that are insensitive to dopamine treatment and is
      not thought to involve frontal cortical DA circuits, unlike PD. We found that
      people with focal dystonia showed intact perceptual decision-making performance
      but impaired use of priors in perceptual decision-making, similar to people with
      PD. Together, the results show a dissociation between motor and cognitive
      performance in people with PD and reveal a novel cognitive impairment,
      independent of sensory and motor impairment, in people with focal dystonia. The
      combined results from people with PD and people with focal dystonia provide
      mechanistic insights into the role of basal ganglia non-dopaminergic circuits in
      perceptual decision-making based on priors.

PMID- 29167329
TI  - Estradiol and Age-Related Bone Loss in Men.

PMID- 29167331
TI  - Spaceflight-Induced Intracranial Hypertension and Visual Impairment:
      Pathophysiology and Countermeasures.
AB  - Visual impairment intracranial pressure (VIIP) syndrome is considered an
      unexplained major risk for future long-duration spaceflight. NASA recently
      redefined this syndrome as Spaceflight-Associated Neuro-ocular Syndrome (SANS).
      Evidence thus reviewed supports that chronic, mildly elevated intracranial
      pressure (ICP) in space (as opposed to more variable ICP with posture and
      activity on Earth) is largely accounted for by loss of hydrostatic pressures and
      altered hemodynamics in the intracranial circulation and the cerebrospinal fluid
      system. In space, an elevated pressure gradient across the lamina cribrosa,
      caused by a chronic but mildly elevated ICP, likely elicits adaptations of
      multiple structures and fluid systems in the eye which manifest themselves as the
      VIIP syndrome. A chronic mismatch between ICP and intraocular pressure (IOP) in
      space may acclimate the optic nerve head, lamina cribrosa, and optic nerve
      subarachnoid space to a condition that is maladaptive to Earth, all contributing
      to the pathogenesis of space VIIP syndrome. Relevant findings help to evaluate
      whether artificial gravity is an appropriate countermeasure to prevent this
      seemingly adverse effect of long-duration spaceflight.

PMID- 29167332
TI  - Redox Regulation of Homeostasis and Proteostasis in Peroxisomes.
AB  - Peroxisomes are highly dynamic intracellular organelles involved in a variety of
      metabolic functions essential for the metabolism of long-chain fatty acids, d
      amino acids, and many polyamines. A byproduct of peroxisomal metabolism is the
      generation, and subsequent detoxification, of reactive oxygen and nitrogen
      species, particularly hydrogen peroxide (H2O2). Because of its relatively low
      reactivity (as a mild oxidant), H2O2 has a comparatively long intracellular half
      life and a high diffusion rate, all of which makes H2O2 an efficient signaling
      molecule. Peroxisomes also have intricate connections to mitochondria, and both
      organelles appear to play important roles in regulating redox signaling pathways.
      Peroxisomal proteins are also subject to oxidative modification and inactivation
      by the reactive oxygen and nitrogen species they generate, but the peroxisomal
      LonP2 protease can selectively remove such oxidatively damaged proteins, thus
      prolonging the useful lifespan of the organelle. Peroxisomal homeostasis must
      adapt to the metabolic state of the cell, by a combination of peroxisome
      proliferation, the removal of excess or badly damaged organelles by autophagy
      (pexophagy), as well as by processes of peroxisome inheritance and motility. More
      recently the tumor suppressors ataxia telangiectasia mutate (ATM) and tuberous
      sclerosis complex (TSC), which regulate mTORC1 signaling, have been found to
      regulate pexophagy in response to variable levels of certain reactive oxygen and
      nitrogen species. It is now clear that any significant loss of peroxisome
      homeostasis can have devastating physiological consequences. Peroxisome
      dysregulation has been implicated in several metabolic diseases, and increasing
      evidence highlights the important role of diminished peroxisomal functions in
      aging processes.

PMID- 29167333
TI  - Authentic Patient-Derived Hepatitis C Virus Infects and Productively Replicates
      in Primary CD4+ and CD8+ T Lymphocytes In Vitro.
AB  - Accumulated evidence indicates that immune cells can support the replication of
      hepatitis C virus (HCV) in infected patients and in culture. However, there is a
      scarcity of data on the degree to which individual immune cell types support HCV
      propagation and on characteristics of virus assembly. We investigated the ability
      of authentic, patient-derived HCV to infect in vitro two closely related but
      functionally distinct immune cell types, CD4+ and CD8+ T lymphocytes, and
      assessed the properties of the virus produced by these cells. The HCV replication
      system in intermittently mitogen-stimulated T cells was adapted to infect primary
      human CD4+ or CD8+ T lymphocytes. HCV replicated in both cell types although at
      significantly higher levels in CD4+ than in CD8+ T cells. Thus, the HCV RNA
      replicative (negative) strand was detected in CD4+ and CD8+ cells at estimated
      mean levels +/- standard errors of the means of 6.7 * 102 +/- 3.8 * 102 and 1.2 *
      102 +/- 0.8 * 102 copies/MUg RNA, respectively (P < 0.0001). Intracellular HCV
      NS5a and/or core proteins were identified in 0.9% of CD4+ and in 1.2% of CD8+ T
      cells. Double staining for NS5a and T cell type-specific markers confirmed that
      transcriptionally competent virus replicated in both cell types. Furthermore, an
      HCV-specific protease inhibitor, telaprevir, inhibited infection in both CD4+ and
      CD8+ cells. The emergence of unique HCV variants and the release of HCV RNA
      reactive particles with biophysical properties different from those of virions in
      plasma inocula suggested that distinct viral particles were assembled, and
      therefore, they may contribute to the pool of circulating virus in infected
      patients.IMPORTANCE Although the liver is the main site of HCV replication,
      infection of the immune system is an intrinsic characteristic of this virus
      independent of whether infection is symptomatic or clinically silent. Many
      fundamental aspects of HCV lymphotropism remain uncertain, including the degree
      to which different immune cells support infection and contribute to virus
      diversity. We show that authentic, patient-derived HCV productively replicates in
      vitro in two closely related but functionally distinct types of T lymphocytes,
      CD4+ and CD8+ cells. The display of viral proteins and unique variants, the
      production of virions with biophysical properties distinct from those in plasma
      serving as inocula, and inhibition of replication by an antiviral agent led us to
      ascertain that both T cell subtypes supported virus propagation. Infection of
      CD4+ and CD8+ T cells, which are central to adaptive antiviral immune responses,
      can directly affect HCV clearance, favor virus persistence, and decisively
      influence the development and progression of hepatitis C.

PMID- 29167334
TI  - Flow Virometry: a Powerful Tool To Functionally Characterize Viruses.
AB  - For several decades, flow cytometry has been a common approach to analyze cells
      and sort them to near-purity. It enables one to probe inner cellular molecules,
      surface receptors, or infected cells. However, the analysis of smaller entities
      such as viruses and exocytic vesicles has been more difficult but is becoming
      mainstream. This has in part been due to the development of new instrumentation
      with resolutions below that of conventional cytometers. It is also attributed to
      the several means employed to fluorescently label viruses, hence enabling them to
      stand out from similarly sized particles representing background noise. Thus far,
      more than a dozen different viruses ranging in size from 40 nm to giant viruses
      have been probed by this approach, which was recently dubbed "flow virometry."
      These studies have collectively highlighted the breadth of the applications of
      this method, which, for example, has elucidated the maturation of dengue virus,
      served as quality control for vaccinia vaccines, and enabled the sorting of
      herpes simplex virus discrete viral particles. The present review focuses on the
      means employed to characterize and sort viruses by this powerful technology and
      on the emerging uses of flow virometry. It similarly addresses some of its
      current challenges and limitations.

PMID- 29167335
TI  - beta-D-N(4)-hydroxycytidine is a potent anti-alphavirus compound that induces
      high level of mutations in viral genome.
AB  - Venezuelan equine encephalitis virus (VEEV) is a representative member of the New
      World alphaviruses. It is transmitted by mosquito vectors and causes highly
      debilitating disease in humans, equides and other vertebrate hosts. Despite a
      continuous public health threat, very few compounds with anti-VEEV activity in
      cell culture and in mouse models have been identified to date, and rapid
      development of virus resistance to some of them has been recorded. In this study,
      we investigated the possibility of using a modified nucleoside analog, beta-D
      N(4)-hydroxycytidine (NHC), as an anti-VEEV agent and defined the mechanism of
      its anti-VEEV activity. The results demonstrate that NHC is a very potent
      antiviral agent. It affects both the release of genome RNA-containing VEE virions
      and their infectivity. Both these antiviral activities are determined by the NHC
      induced accumulation of mutations in virus-specific RNAs. The antiviral effect is
      most prominent when NHC is applied early in the infectious process, during
      amplification of negative and positive strand RNAs in the infected cells. Most
      importantly, only a low level resistance of VEEV to NHC can be developed, and it
      requires acquisition and cooperative function of more than one mutation in nsP4.
      These adaptive mutations are closely located in the same segment of nsP4. Our
      data suggest that NHC is more potent than ribavirin as an anti-VEEV agent, and
      likely can be used to treat other alphavirus infections.IMPORTANCEVenezuelan
      equine encephalitis virus (VEEV) can cause widespread epidemics among humans and
      domestic animals. VEEV infections result in severe meningoencephalitis and long
      term sequilae. No approved therapeutics exist for treatment of VEEV infections.
      Our study demonstrates that N-hydroxycytidine (NHC) is a very potent anti-VEEV
      compound, with the EC50 being below 1 MUM. The mechanism of NHC antiviral
      activity is based on induction of high mutation rates in the viral genome.
      Accordingly, NHC treatment affects both the rates of particle release and the
      particle infectivity. Most importantly, in contrast to most of the anti
      alphavirus drugs that are under development, resistance of VEEV to NHC develops
      very inefficiently. Even low levels of resistance require acquisition of multiple
      mutations in the gene of VEEV-specific RNA-dependent RNA polymerase, nsP4.

PMID- 29167336
TI  - Insight into the Roles of E3 Ubiquitin Ligase c-Cbl, ESCRT Machinery, and Host
      Cell Signaling in Kaposi's Sarcoma-Associated Herpesvirus Entry and Trafficking.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) in vitro infection of dermal
      endothelial cells begins with its binding to host cell surface receptor molecules
      such as heparan sulfate (HS), integrins (alpha3beta1, alphaVbeta3, and
      alphaVbeta5), xCT, and EphA2 receptor tyrosine kinase (EphA2R). These initial
      events initiate dynamic host protein-protein interactions involving a
      multimolecular complex of receptors, signal molecules (focal adhesion kinase
      [FAK], Src, phosphatidylinositol 3-kinase [PI3-K], and RhoA-GTPase), adaptors (c
      Cbl, CIB1, Crk, p130Cas, and GEF-C3G), actin, and myosin II light chain that lead
      to virus entry via macropinocytosis. Here we discuss how KSHV hijacks c-Cbl, an
      E3 ubiquitin ligase, to monoubiquitinate the receptors and actin, which acts like
      a marker for trafficking (similar to zip codes), resulting in the recruitment of
      the members of the host endosomal sorting complexes required for transport
      (ESCRT) Hrs, Tsg101, EAP45, and the CHMP5 and -6 proteins (zip code readers)
      recognizing the ubiquitinated protein and adaptor machinery to traffic through
      the different endosomal compartments in the cytoplasm to initiate the
      macropinocytic process and infection.

PMID- 29167337
TI  - Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B*27:05-
      and -B*27:02-Mediated Control of HIV-1 Infection.
AB  - The well-characterized association between HLA-B*27:05 and protection against HIV
      disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+
      T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and
      polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the
      3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02
      on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV.
      Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are
      associated with slower disease progression and lower viral loads. The effect of
      HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In
      contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted
      CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol
      KY9 subdominant and Gag KK10 further subdominant. This selection was driven by
      structural differences in the F pocket, mediated by a polymorphism between these
      two HLA alleles at position 81. Analysis of autologous virus sequences showed
      that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses
      impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects,
      there is no Nef VW9-mediated selection pressure. These studies demonstrate that
      HLA-B*27:02 mediates protection against HIV disease progression that is at least
      as strong as or stronger than that mediated by HLA-B*27:05. In combination with
      the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV
      specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9
      specific response is additionally present and immunodominant in HLA-B*27:02
      positive subjects, mediated through a polymorphism at residue 81 in the F pocket,
      that contributes to selection pressure against HIV.IMPORTANCE CD8+ T cells play a
      central role in successful control of HIV infection and have the potential also
      to mediate the eradication of viral reservoirs of infection. The principal means
      by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01,
      slow HIV disease progression is believed to be via the particular HIV-specific
      CD8+ T cell responses restricted by those alleles. We focus here on HLA-B*27:05,
      one of the best-characterized protective HLA molecules, and the closely related
      HLA-B*27:02, which differs by only 3 amino acids and which has not been well
      studied in relation to control of HIV infection. We show that HLA-B*27:02 is also
      protective against HIV disease progression, but the CD8+ T-cell immunodominance
      hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These
      findings indicate that the immunodominant HLA-B*27:02-restricted Nef response
      adds to protection mediated by the Gag and Pol specificities that dominate anti
      HIV CD8+ T-cell activity in HLA-B*27:05-positive subjects.

PMID- 29167339
TI  - Identification and Functional Characterization of Phosphorylation Sites of the
      Human Papillomavirus 31 E8^E2 Protein.
AB  - The papillomavirus E2 protein regulates transcription, replication, and nuclear
      retention of viral genomes. Phosphorylation of E2 in the hinge region has been
      suggested to modulate protein stability, DNA-binding activity, and chromosomal
      attachment. The papillomavirus E8^E2 protein shares the hinge domain with E2 and
      acts as a repressor of viral replication. Mass spectrometry analyses of human
      papillomavirus 31 (HPV31) E8^E2 and E2 proteins identify phosphorylated S78, S81,
      and S100 in E8^E2 and S266 and S269 in E2 in their hinge regions. Phos-tag
      analyses of wild-type and mutant proteins indicate that S78 is a major
      phosphorylation site in E8^E2, but the corresponding S266 in E2 is not.
      Phosphorylation at S78 regulates E8^E2's repression activity of reporter
      constructs, whereas the corresponding E2 mutants do not display a phenotype.
      Phosphorylation at S78 does not alter E8^E2's protein stability, nuclear
      localization, or binding to DNA or to cellular NCoR/SMRT complexes. Surprisingly,
      in the context of HPV31 genomes, mutation of E8^E2 S78 does not modulate viral
      replication or transcription in undifferentiated or differentiated cells.
      However, comparative transcriptome analyses of differentiated HPV31 E8^E2 S78A
      and S78E cell lines reveal that the expression of a small number of cellular
      genes is changed. Validation experiments suggest that the transcription of the
      cellular LYPD2 gene is altered in a phospho-S78 E8^E2-dependent manner. In
      summary, our data suggest that phosphorylation of S78 in E8^E2 regulates its
      repression activity by a novel mechanism, and this seems to be important for the
      modulation of host cell gene expression but not viral replication.IMPORTANCE
      Posttranslational modification of viral proteins is a common feature to modulate
      their activities. Phosphorylation of serine residues S298 and S301 in the hinge
      region of the bovine papillomavirus type 1 E2 protein has been shown to restrict
      viral replication. The papillomavirus E8^E2 protein shares the hinge domain with
      E2 and acts as a repressor of viral replication. A large fraction of HPV31 E8^E2
      is phosphorylated at S78 in the hinge region, and this is important for E8^E2's
      repression activity. Surprisingly, phosphorylation at S78 in E8^E2 has no impact
      on viral replication in tissue culture but rather seems to modulate the
      expression of a small number of cellular genes. This may indicate that
      phosphorylation of viral transcription factors serves to broaden their target
      gene specificity.

PMID- 29167338
TI  - Inhibition of Cytosolic Phospholipase A2alpha Impairs an Early Step of
      Coronavirus Replication in Cell Culture.
AB  - Coronavirus replication is associated with intracellular membrane rearrangements
      in infected cells, resulting in the formation of double-membrane vesicles (DMVs)
      and other membranous structures that are referred to as replicative organelles
      (ROs). The latter provide a structural scaffold for viral
      replication/transcription complexes (RTCs) and help to sequester RTC components
      from recognition by cellular factors involved in antiviral host responses. There
      is increasing evidence that plus-strand RNA (+RNA) virus replication, including
      RO formation and virion morphogenesis, affects cellular lipid metabolism and
      critically depends on enzymes involved in lipid synthesis and processing. Here,
      we investigated the role of cytosolic phospholipase A2alpha (cPLA2alpha) in
      coronavirus replication using a low-molecular-weight nonpeptidic inhibitor,
      pyrrolidine-2 (Py-2). The inhibition of cPLA2alpha activity, which produces
      lysophospholipids (LPLs) by cleaving at the sn-2 position of phospholipids, had
      profound effects on viral RNA and protein accumulation in human coronavirus 229E
      infected Huh-7 cells. Transmission electron microscopy revealed that DMV
      formation in infected cells was significantly reduced in the presence of the
      inhibitor. Furthermore, we found that (i) viral RTCs colocalized with LPL
      containing membranes, (ii) cellular LPL concentrations were increased in
      coronavirus-infected cells, and (iii) this increase was diminished in the
      presence of the cPLA2alpha inhibitor Py-2. Py-2 also displayed antiviral
      activities against other viruses representing the Coronaviridae and Togaviridae
      families, while members of the Picornaviridae were not affected. Taken together,
      the study provides evidence that cPLA2alpha activity is critically involved in
      the replication of various +RNA virus families and may thus represent a candidate
      target for broad-spectrum antiviral drug development.IMPORTANCE Examples of
      highly conserved RNA virus proteins that qualify as drug targets for broad
      spectrum antivirals remain scarce, resulting in increased efforts to identify and
      specifically inhibit cellular functions that are essential for the replication of
      RNA viruses belonging to different genera and families. The present study
      supports and extends previous conclusions that enzymes involved in cellular lipid
      metabolism may be tractable targets for broad-spectrum antivirals. We obtained
      evidence to show that a cellular phospholipase, cPLA2alpha, which releases fatty
      acid from the sn-2 position of membrane-associated glycerophospholipids, is
      critically involved in coronavirus replication, most likely by producing
      lysophospholipids that are required to form the specialized membrane compartments
      in which viral RNA synthesis takes place. The importance of this enzyme in
      coronavirus replication and DMV formation is supported by several lines of
      evidence, including confocal and electron microscopy, viral replication, and
      lipidomics studies of coronavirus-infected cells treated with a highly specific
      cPLA2alpha inhibitor.

PMID- 29167330
TI  - Endothelial Cell Metabolism.
AB  - Endothelial cells (ECs) are more than inert blood vessel lining material.
      Instead, they are active players in the formation of new blood vessels
      (angiogenesis) both in health and (life-threatening) diseases. Recently, a new
      concept arose by which EC metabolism drives angiogenesis in parallel to well
      established angiogenic growth factors (e.g., vascular endothelial growth factor).
      6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3-driven glycolysis
      generates energy to sustain competitive behavior of the ECs at the tip of a
      growing vessel sprout, whereas carnitine palmitoyltransferase 1a-controlled fatty
      acid oxidation regulates nucleotide synthesis and proliferation of ECs in the
      stalk of the sprout. To maintain vascular homeostasis, ECs rely on an intricate
      metabolic wiring characterized by intracellular compartmentalization, use
      metabolites for epigenetic regulation of EC subtype differentiation, crosstalk
      through metabolite release with other cell types, and exhibit EC subtype-specific
      metabolic traits. Importantly, maladaptation of EC metabolism contributes to
      vascular disorders, through EC dysfunction or excess angiogenesis, and presents
      new opportunities for anti-angiogenic strategies. Here we provide a comprehensive
      overview of established as well as newly uncovered aspects of EC metabolism.

PMID- 29167340
TI  - Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To
      Limit Essential Viral Functions.
AB  - Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double
      stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral
      replication, the genome is imported through the nuclear pore complex associated
      with viral core proteins. Until now, the role of these incoming virion proteins
      during the early phase of infection was poorly understood. The core protein V is
      speculated to bridge the core and the surrounding capsid. It binds the genome in
      a sequence-independent manner and localizes in the nucleus of infected cells,
      accumulating at nucleoli. Here, we show that protein V contains conserved SUMO
      conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced
      SUMOylation of the protein; thus, protein V represents a novel target of the host
      SUMOylation machinery. To understand the role of protein V SUMO posttranslational
      modification during productive HAdV infection, we generated a replication
      competent HAdV with SCM mutations within the protein V coding sequence.
      Phenotypic analyses revealed that these SCM mutations are beneficial for
      adenoviral replication. Blocking protein V SUMOylation at specific sites shifts
      the onset of viral DNA replication to earlier time points during infection and
      promotes viral gene expression. Simultaneously, the altered kinetics within the
      viral life cycle are accompanied by more efficient proteasomal degradation of
      host determinants and increased virus progeny production than that observed
      during wild-type infection. Taken together, our studies show that protein V
      SUMOylation reduces virus growth; hence, protein V SUMOylation represents an
      important novel aspect of the host antiviral strategy to limit virus replication
      and thereby points to potential intervention strategies.IMPORTANCE Many decades
      of research have revealed that HAdV structural proteins promote viral entry and
      mainly physical stability of the viral genome in the capsid. Our work over the
      last years showed that this concept needs expansion as the functions are more
      diverse. We showed that capsid protein VI regulates the antiviral response by
      modulation of the transcription factor Daxx during infection. Moreover, core
      protein VII interacts with SPOC1 restriction factor, which is beneficial for
      efficient viral gene expression. Here, we were able to show that core protein V
      also represents a novel substrate of the host SUMOylation machinery and contains
      several conserved SCMs; mutation of these consensus motifs reduced SUMOylation of
      the protein. Unexpectedly, we observed that introducing these mutations into HAdV
      promotes adenoviral replication. In conclusion, we offer novel insights into
      adenovirus core proteins and provide evidence that SUMOylation of HAdV factors
      regulates replication efficiency.

PMID- 29167341
TI  - Novel Synthesis and Phenotypic Analysis of Mutant Clouds for Hepatitis E Virus
      Genotype 1.
AB  - Many RNA viruses exist as an ensemble of genetically diverse, replicating
      populations known as a mutant cloud. The genetic diversity (cloud size) and
      composition of this mutant cloud may influence several important phenotypic
      features of the virus, including its replication capacity. We applied a
      straightforward, bacterium-free approach using error-prone PCR coupled with
      reverse genetics to generate infectious mutant RNA clouds with various levels of
      genetic diversity from a genotype 1 strain of hepatitis E virus (HEV). Cloning
      and sequencing of a genomic fragment encompassing 70% of open reading frame 1
      (ORF1) or of the full genome from variants in the resultant clouds showed the
      occurrence of nucleotide mutations at a frequency on the order of 10-3 per
      nucleotide copied and the existence of marked genetic diversity, with a high
      normalized Shannon entropy value. The mutant clouds showed transient replication
      in cell culture, while wild-type HEV did not. Cross-sectional data from these
      cell cultures supported the existence of differential effects of clouds of
      various sizes and compositions on phenotypic characteristics, such as the
      replication level of (+)-RNA progeny, the amounts of double-stranded RNA (a
      surrogate for the rate of viral replication) and ORF1 protein, and the expression
      of interferon-stimulated genes. Since mutant cloud size and composition
      influenced the viral phenotypic properties, a better understanding of this
      relationship may help to provide further insights into virus evolution and
      prediction of emerging viral diseases.IMPORTANCE Several biological or practical
      limitations currently prevent the study of phenotypic behavior of a mutant cloud
      in vitro We developed a simple and rapid method for synthesizing mutant clouds of
      hepatitis E virus (HEV), a single-stranded (+)-RNA [ss(+) RNA] virus, with
      various and controllable levels of genetic diversity, which could then be used in
      a cell culture system to study the effects of cloud size and composition on viral
      phenotype. In a cross-sectional analysis, we demonstrated that a particular
      mutant cloud which had an extremely high genetic diversity had a replication rate
      exceeding that of wild-type HEV. This method should thus provide a useful model
      for understanding the phenotypic behavior of ss(+) RNA viruses.

PMID- 29167343
TI  - Ubiquitination of the Cytoplasmic Domain of Influenza A Virus M2 Protein Is
      Crucial for Production of Infectious Virus Particles.
AB  - Virus replication is mediated by interactions between the virus and host. Here,
      we demonstrate that influenza A virus membrane protein 2 (M2) can be
      ubiquitinated. The lysine residue at position 78, which is located in the
      cytoplasmic domain of M2, is essential for M2 ubiquitination. An M2-K78R (Lys78
      >Arg78) mutant, which produces ubiquitination-deficient M2, showed a severe
      defect in the production of infectious virus particles. M2-K78R mutant progeny
      contained more hemagglutinin (HA) proteins, less viral RNAs, and less internal
      viral proteins, including M1 and NP, than the wild-type virus. Furthermore, most
      of the M2-K78R mutant viral particles lacked viral ribonucleoproteins upon
      examination by electron microscopy and exhibited slightly lower densities. We
      also found that mutant M2 colocalized with the M1 protein to a lesser extent than
      for the wild-type virus. These findings may account for the reduced incorporation
      of viral ribonucleoprotein into virions. By blocking the second round of virus
      infection, we showed that the M2 ubiquitination-defective mutant exhibited normal
      levels of virus replication during the first round of infection, thereby proving
      that M2 ubiquitination is involved in the virus production step. Finally, we
      found that the M2-K78R mutant virus induced autophagy and apoptosis earlier than
      did the wild-type virus. Collectively, these results suggest that M2
      ubiquitination plays an important role in infectious virus production by
      coordinating the efficient packaging of the viral genome into virus particles and
      the timing of virus-induced cell death.IMPORTANCE Annual epidemics and recurring
      pandemics of influenza viruses represent very high global health and economic
      burdens. The influenza virus M2 protein has been extensively studied for its
      important roles in virus replication, particularly in virus entry and release.
      Rimantadine, one of the most commonly used antiviral drugs, binds to the channel
      lumen near the N terminus of M2 proteins. However, viruses that are resistant to
      rimantadine have emerged. M2 undergoes several posttranslational modifications,
      such as phosphorylation and palmitoylation. Here, we reveal that ubiquitination
      mediates the functional role of M2. A ubiquitination-deficient M2 mutant
      predominately produced virus particles either lacking viral ribonucleoproteins or
      containing smaller amounts of internal viral components, resulting in lower
      infectivity. Our findings offer insights into the mechanism of influenza virus
      morphogenesis, particularly the functional role of M1-M2 interactions in viral
      particle assembly, and can be applied to the development of new influenza
      therapies.

PMID- 29167342
TI  - Antibodies Directed toward Neuraminidase N1 Control Disease in a Mouse Model of
      Influenza.
AB  - There is increasing evidence to suggest that antibodies directed toward influenza
      A virus (IAV) neuraminidase (NA) are an important correlate of protection against
      influenza in humans. Moreover, the potential of NA-specific antibodies to provide
      broader protection than conventional hemagglutinin (HA) antibodies has been
      recognized. Here, we describe the isolation of two monoclonal antibodies, N1-7D3
      and N1-C4, directed toward the N1 NA. N1-7D3 binds to a conserved linear epitope
      in the membrane-distal, carboxy-terminal part of the NA and reacted with the NA
      of seasonal H1N1 isolates ranging from 1977 to 2007 and the 2009 H1N1pdm virus,
      as well as A/Vietnam/1194/04 (H5N1). However, N1-7D3 lacked NA inhibition (NI)
      activity and the ability to protect BALB/c mice against a lethal challenge with a
      range of H1N1 viruses. Conversely, N1-C4 bound to a conformational epitope that
      is conserved between two influenza virus subtypes, 2009 H1N1pdm and H5N1 IAV, and
      displayed potent in vitro antiviral activity mediating both NI and plaque size
      reduction. Moreover, N1-C4 could provide heterosubtypic protection in BALB/c mice
      against a lethal challenge with 2009 H1N1pdm or H5N1 virus. Glutamic acid residue
      311 in the NA was found to be critical for the NA binding and antiviral activity
      of monoclonal antibody N1-C4. Our data provide further evidence for cross
      protective epitopes within the N1 subtype and highlight the potential of NA as an
      important target for vaccine and therapeutic approaches.IMPORTANCE Influenza
      remains a worldwide burden on public health. As such, the development of novel
      vaccines and therapeutics against influenza virus is crucial. Human challenge
      studies have recently highlighted the importance of antibodies directed toward
      the viral neuraminidase (NA) as an important correlate of reduced influenza
      associated disease severity. Furthermore, there is evidence that anti-NA
      antibodies can provide broader protection than antibodies toward the viral
      hemagglutinin. Here, we describe the isolation and detailed characterization of
      two N1 NA-specific monoclonal antibodies. One of these monoclonal antibodies
      broadly binds N1-type NAs, and the second displays NA inhibition and in vitro and
      in vivo antiviral activity against 2009 H1N1pdm and H5N1 influenza viruses. These
      two new anti-NA antibodies contribute to our understanding of the antigenic
      properties and protective potential of the influenza virus NA antigen.

PMID- 29167344
TI  - Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies
      against Influenza A(H7N9) Virus Infection.
AB  - The fifth wave of A(H7N9) virus infection in China from 2016 to 2017 caused great
      concern due to the large number of individuals infected, the isolation of drug
      resistant viruses, and the emergence of highly pathogenic strains. Antibodies
      against neuraminidase (NA) provide added benefit to hemagglutinin-specific
      immunity and may be important contributors to the effectiveness of A(H7N9)
      vaccines. We generated a panel of mouse monoclonal antibodies (MAbs) to identify
      antigenic domains on NA of the novel A(H7N9) virus and compared their functional
      properties. The loop formed in the region of residue 250 (250 loop) and the
      domain formed by the loops containing residues 370, 400, and 430 were identified
      as major antigenic regions. MAbs 1E8, 2F6, 10F4, and 11B2, which recognize these
      two antigenic domains, were characterized in depth. These four MAbs differ in
      their abilities to inhibit cleavage of small and large substrates (methyl
      umbelliferyl-acetyl neuraminic acid [MU-NANA] and fetuin, respectively) in NA
      inhibition assays. 1E8 and 11B2 did not inhibit NA cleavage of either MU-NANA or
      fetuin, and 2F6 inhibited cleavage of fetuin alone, whereas 10F4 inhibited
      cleavage of both substrates. All four MAbs reduced the in vitro spread of viruses
      carrying either the wild-type N9 or N9 with antiviral-resistant mutations but to
      different degrees. These MAbs have different in vivo levels of effectiveness:
      10F4 was the most effective in protecting mice against challenge with A(H7N9)
      virus, 2F6 was less effective, and 11B2 failed to protect BALB/c mice at the
      doses tested. Our study confirms that NA-specific antibodies can protect against
      A(H7N9) infection and suggests that in vitro properties can be used to rank
      antibodies with therapeutic potential.IMPORTANCE The novel A(H7N9) viruses that
      emerged in China in 2013 continue to infect humans, with a high fatality rate.
      The most recent outbreak resulted in a larger number of human cases than previous
      epidemic waves. Due to the absence of a licensed vaccine and the emergence of
      drug-resistant viruses, there is a need to develop alternative approaches to
      prevent or treat A(H7N9) infection. We have made a panel of mouse monoclonal
      antibodies (MAbs) specific for neuraminidase (NA) of A(H7N9) viruses; some of
      these MAbs are effective in inhibiting viruses that are resistant to antivirals
      used to treat A(H7N9) patients. Binding avidity, inhibition of NA activity, and
      plaque formation correlated with the effectiveness of these MAbs to protect mice
      against lethal A(H7N9) virus challenge. This study identifies in vitro measures
      that can be used to predict the in vivo efficacy of NA-specific antibodies,
      providing a way to select MAbs for further therapeutic development.

PMID- 29167345
TI  - Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts.
AB  - Merkel cell polyomavirus (MCPyV) is the first polyomavirus to be associated with
      human cancer. Mechanistic studies attempting to fully elucidate MCPyV's oncogenic
      mechanisms have been hampered by the lack of animal models for MCPyV infection.
      In this study, we examined the ability of MCPyV-GFP pseudovirus (containing a
      green fluorescent protein [GFP] reporter construct), MCPyV recombinant virions,
      and several MCPyV chimeric viruses to infect dermal fibroblasts isolated from
      various model animals, including mouse (Mus musculus), rabbit (Oryctolagus
      cuniculus), rat (Rattus norvegicus), chimpanzee (Pan troglodytes), rhesus macaque
      (Macaca mulatta), patas monkey (Erythrocebus patas), common woolly monkey
      (Lagothrix lagotricha), red-chested mustached tamarin (Saguinus labiatus), and
      tree shrew (Tupaia belangeri). We found that MCPyV-GFP pseudovirus was able to
      enter the dermal fibroblasts of all species tested. Chimpanzee dermal fibroblasts
      were the only type that supported vigorous MCPyV gene expression and viral
      replication, and they did so to a level beyond that of human dermal fibroblasts.
      We further demonstrated that both human and chimpanzee dermal fibroblasts produce
      infectious MCPyV virions that can successfully infect new cells. In addition, rat
      dermal fibroblasts supported robust MCPyV large T antigen expression after
      infection with an MCPyV chimeric virus in which the entire enhancer region of the
      MCPyV early promoter has been replaced with the simian virus 40 (SV40) analog.
      Our results suggest that viral transcription and/or replication events represent
      the major hurdle for MCPyV cross-species transmission. The capacity of rat dermal
      fibroblasts to support MCPyV early gene expression suggests that the rat is a
      candidate model organism for studying viral oncogene function during Merkel cell
      carcinoma (MCC) oncogenic progression.IMPORTANCE MCPyV plays an important role in
      the development of a highly aggressive form of skin cancer, Merkel cell carcinoma
      (MCC). With the increasing number of MCC diagnoses, there is a need to better
      understand the virus and its oncogenic potential. However, studies attempting to
      fully elucidate MCPyV's oncogenic mechanisms have been hampered by the lack of
      animal models for MCPyV infection. To pinpoint the best candidate for developing
      an MCPyV infection animal model, we examined MCPyV's ability to infect dermal
      fibroblasts isolated from various established model animals. Of the animal cell
      types we tested, chimpanzee dermal fibroblasts were the only isolates that
      supported the full MCPyV infectious cycle. To overcome the infection blockade in
      the other model animals, we constructed chimeric viruses that achieved robust
      MCPyV entry and oncogene expression in rat fibroblasts. Our results suggest that
      the rat may serve as an in vivo model to study MCV oncogenesis.

PMID- 29167346
TI  - Glycine Zipper Motifs in Hepatitis C Virus Nonstructural Protein 4B Are Required
      for the Establishment of Viral Replication Organelles.
AB  - Hepatitis C virus (HCV) RNA replication occurs in tight association with
      remodeled host cell membranes, presenting as cytoplasmic accumulations of single
      , double-, and multimembrane vesicles in infected cells. Formation of these so
      called replication organelles is mediated by a complex interplay of host cell
      factors and viral replicase proteins. Of these, nonstructural protein 4B (NS4B),
      an integral transmembrane protein, appears to play a key role, but little is
      known about the molecular mechanisms of how this protein contributes to organelle
      biogenesis. Using forward and reverse genetics, we identified glycine zipper
      motifs within transmembrane helices 2 and 3 of NS4B that are critically involved
      in viral RNA replication. Foerster resonance energy transfer analysis revealed
      the importance of the glycine zippers in NS4B homo- and heterotypic self
      interactions. Additionally, ultrastructural analysis using electron microscopy
      unraveled a prominent role of glycine zipper residues for the subcellular
      distribution and the morphology of HCV-induced double-membrane vesicles. Notably,
      loss-of-function NS4B glycine zipper mutants prominently induced single-membrane
      vesicles with secondary invaginations that might represent an arrested
      intermediate state in double-membrane vesicle formation. These findings highlight
      a so-far-unknown role of glycine residues within the membrane integral core
      domain for NS4B self-interaction and functional as well as structural integrity
      of HCV replication organelles.IMPORTANCE Remodeling of the cellular endomembrane
      system leading to the establishment of replication organelles is a hallmark of
      positive-strand RNA viruses. In the case of HCV, expression of the nonstructural
      proteins induces the accumulation of double-membrane vesicles that likely arise
      from a concerted action of viral and coopted cellular factors. However, the
      underlying molecular mechanisms are incompletely understood. Here, we identify
      glycine zipper motifs within HCV NS4B transmembrane segments 2 and 3 that are
      crucial for the protein's self-interaction. Moreover, glycine residues within
      NS4B transmembrane helices critically contribute to the biogenesis of functional
      replication organelles and, thus, efficient viral RNA replication. These results
      reveal how glycine zipper motifs in NS4B contribute to structural and functional
      integrity of the HCV replication organelles and, thus, viral RNA replication.

PMID- 29167348
TI  - Pregnancy is detected via odour in a wild cooperative breeder.
AB  - Among mammals, scent has long been known to encode oestrus; however, in many
      species, detecting pregnancy may also be important in terms of both competition
      and mate-choice. Here, we show, through odour presentation experiments, that
      pregnancy is discernible via scent by both sexes in the cooperatively breeding
      banded mongoose, Mungos mungo Males spent more time investigating and were more
      likely to scent mark the odours of non-pregnant females, compared to pregnant
      females. Females showed increased levels of scent marking when odours were of the
      same reproductive state as themselves. These results present the first direct
      demonstration that pregnancy is detectable via scent in wild cooperative
      breeders. Detecting pregnancy may be particularly important in cooperative
      breeders as, in addition to the competition between males for receptive mates,
      there is also intense competition between females for access to alloparental
      care. Consequently, dominant females benefit from targeting reproductive
      suppression towards subordinates that represent direct threats, such as pregnant
      females.

PMID- 29167347
TI  - Novel Role of vBcl2 in the Virion Assembly of Kaposi's Sarcoma-Associated
      Herpesvirus.
AB  - The viral Bcl-2 homolog (vBcl2) of Kaposi's sarcoma-associated herpesvirus (KSHV)
      displays efficient antiapoptotic and antiautophagic activity through its central
      BH3 domain, which functions to prolong the life span of virus-infected cells and
      ultimately enhances virus replication and latency. Independent of its
      antiapoptotic and antiautophagic activity, vBcl2 also plays an essential role in
      KSHV lytic replication through its amino-terminal amino acids (aa) 11 to 20.
      Here, we report a novel molecular mechanism of vBcl2-mediated regulation of KSHV
      lytic replication. vBcl2 specifically bound the tegument protein open reading
      frame 55 (ORF55) through its amino-terminal aa 11 to 20, allowing their
      association with virions. Consequently, the vBcl2 peptide derived from vBcl2 aa
      11 to 20 effectively disrupted the interaction between vBcl2 and ORF55,
      inhibiting the incorporation of the ORF55 tegument protein into virions. This
      study provides new insight into vBcl2's function in KSHV virion assembly that is
      separable from its inhibitory role in host apoptosis and autophagy.IMPORTANCE
      KSHV, an important human pathogen accounting for a large percentage of virally
      caused cancers worldwide, has evolved a variety of stratagems for evading host
      immune responses to establish lifelong persistent infection. Upon viral
      infection, infected cells can go through programmed cell death, including
      apoptosis and autophagy, which plays an effective role in antiviral responses. To
      counter the host response, KSHV vBcl2 efficiently blocks apoptosis and autophagy
      to persist for the life span of virus-infected cells. Besides its anti-programmed
      cell-death activity, vBcl2 also interacts with the ORF55 tegument protein for
      virion assembly in infected cells. Interestingly, the vBcl2 peptide disrupts the
      vBcl2-ORF55 interaction and effectively inhibits KSHV virion assembly. This study
      indicates that KSHV vBcl2 harbors at least three genetically separable functions
      to modulate both host cell death signaling and virion production and that the
      vBcl2 peptide can be developed as an anti-KSHV therapeutic application.

PMID- 29167349
TI  - Left-handedness and time pressure in elite interactive ball games.
AB  - According to the fighting hypothesis, frequency-dependent selection gives
      relatively rarer left-handers a competitive edge in duel-like contests and is
      suggested as one mechanism that ensured the stable maintenance of handedness
      polymorphism in humans. Overrepresentation of left-handers exclusively in
      interactive sports seems to support the hypothesis. Here, by referring to data on
      interactive ball sports, I propose that a left-hander's advantage is linked to
      the sports' underlying time pressure. The prevalence of left-handers listed in
      elite rankings increased from low (8.7%) to high (30.39%) time pressure sports
      and a distinct left-hander overrepresentation was only found in the latter (i.e.
      baseball, cricket and table tennis). This indicates that relative rarity and the
      interactive nature of a contest are not sufficient per se to evoke a left-hander
      advantage. Refining the fighting hypothesis is suggested to facilitate prediction
      and experimental verification of when and why negative frequency-dependent
      selection may benefit left-handedness.

PMID- 29167350
TI  - Safinamide Differentially Modulates In Vivo Glutamate and GABA Release in the Rat
      Hippocampus and Basal Ganglia.
AB  - Safinamide has been recently approved as an add-on to levodopa therapy for
      Parkinson disease. In addition to inhibiting monoamine oxidase type B, it blocks
      sodium channels and modulates glutamate (Glu) release in vitro. Since this
      property might contribute to the therapeutic action of the drug, we undertook the
      present study to investigate whether safinamide inhibits Glu release also in vivo
      and whether this effect is consistent across different brain areas and is
      selective for glutamatergic neurons. To this aim, in vivo microdialysis was used
      to monitor the spontaneous and veratridine-induced Glu and GABA release in the
      hippocampus and basal ganglia of naive, awake rats. Brain levels of safinamide
      were measured as well. To shed light on the mechanisms underlying the effect of
      safinamide, sodium currents were measured by patch-clamp recording in rat
      cortical neurons. Safinamide maximally inhibited the veratridine-induced Glu and
      GABA release in hippocampus at 15 mg/kg, which reached free brain concentrations
      of 1.89-1.37 uM. This dose attenuated veratridine-stimulated Glu (but not GABA)
      release in subthalamic nucleus, globus pallidus, and substantia nigra reticulata,
      but not in striatum. Safinamide was ineffective on spontaneous neurotransmitter
      release. In vitro, safinamide inhibited sodium channels, showing a greater
      affinity at depolarized (IC50 = 8 uM) than at resting (IC50 = 262 uM) potentials.
      We conclude that safinamide inhibits in vivo Glu release from stimulated nerve
      terminals, likely via blockade of sodium channels at subpopulations of neurons
      with specific firing patterns. These data are consistent with the anticonvulsant
      and antiparkinsonian actions of safinamide and provide support for the
      nondopaminergic mechanism of its action.

PMID- 29167352
TI  - Two spatially distinct kinesin-14 proteins, Pkl1 and Klp2, generate collaborative
      inward forces against kinesin-5 Cut7 in S. pombe.
AB  - Kinesin motors play central roles in bipolar spindle assembly. In many
      eukaryotes, spindle pole separation is driven by kinesin-5, which generates
      outward force. This outward force is balanced by antagonistic inward force
      elicited by kinesin-14 and/or dynein. In fission yeast, two kinesin-14 proteins,
      Pkl1 and Klp2, play an opposing role against the kinesin-5 motor protein Cut7.
      However, how the two kinesin-14 proteins coordinate individual activities remains
      elusive. Here, we show that although deletion of either pkl1 or klp2 rescues
      temperature-sensitive cut7 mutants, deletion of only pkl1 can bypass the
      lethality caused by cut7 deletion. Pkl1 is tethered to the spindle pole body,
      whereas Klp2 is localized along the spindle microtubule. Forced targeting of Klp2
      to the spindle pole body, however, compensates for Pkl1 functions, indicating
      that cellular localizations, rather than individual motor specificities,
      differentiate between the two kinesin-14 proteins. Interestingly, human kinesin
      14 (KIFC1 or HSET) can replace either Pkl1 or Klp2. Moreover, overproduction of
      HSET induces monopolar spindles, reminiscent of the phenotype of Cut7
      inactivation. Taken together, this study has uncovered the biological mechanism
      whereby two different Kinesin-14 motor proteins exert their antagonistic roles
      against kinesin-5 in a spatially distinct manner.

PMID- 29167351
TI  - Longitudinal FGF23 Trajectories and Mortality in Patients with CKD.
AB  - Elevated fibroblast growth factor 23 (FGF23) levels, measured at a single time,
      are strongly associated with increased risk of mortality in patients with CKD.
      There are minimal data on serial FGF23 measurements in CKD. In a prospective case
      cohort study of the Chronic Renal Insufficiency Cohort, we measured FGF23 at two
      to five annual time points (mean 4.0+/-1.2) in a randomly selected subcohort of
      1135 participants, of whom 203 died, and all remaining 390 participants who died
      through mid-2013. Higher FGF23 was independently associated with increased risk
      of death in multivariable-adjusted analyses of time-varying FGF23 (hazard ratio
      per 1-SD increase in ln-transformed FGF23, 1.84; 95% CI, 1.67 to 2.03). Median
      FGF23 was stable over 5 years of follow-up, but its gradually right-skewed
      distribution suggested a subpopulation with markedly elevated FGF23. Trajectory
      analysis revealed three distinct trajectories: stable FGF23 in the majority of
      participants (slope of lnFGF23 per year =0.03, 95% CI, 0.02 to 0.04, n=724) and
      smaller subpopulations with slowly (slope=0.14, 95% CI, 0.12 to 0.16, n=486) or
      rapidly (slope=0.46, 95% CI, 0.38 to 0.54, n=99) rising levels. Compared with
      stable FGF23, participants with slowly rising FGF23 trajectories were at 4.49
      fold higher risk of death (95% CI, 3.17 to 6.35) and individuals with rapidly
      rising FGF23 trajectories were at 15.23-fold higher risk of death (95% CI, 8.24
      to 28.14) in fully adjusted analyses. Trajectory analyses that used four or three
      annual FGF23 measurements yielded qualitatively similar results. In conclusion,
      FGF23 levels are stable over time in the majority of patients with CKD, but
      serial measurements identify subpopulations with rising levels and exceptionally
      high risk of death.

PMID- 29167353
TI  - Coordinated Regulation of Hypocotyl Cell Elongation by Light and Ethylene through
      a Microtubule Destabilizing Protein.
AB  - Precise regulation of hypocotyl cell elongation is essential for plant growth and
      survival. Light suppresses hypocotyl elongation by degrading transcription factor
      phytochrome-interacting factor 3 (PIF3), whereas the phytohormone ethylene
      promotes hypocotyl elongation by activating PIF3. However, the underlying
      mechanisms regarding how these two pathways coordinate downstream effectors to
      mediate hypocotyl elongation are largely unclear. In this study, we identified
      the novel Microtubule-Destabilizing Protein 60 (MDP60), which plays a positive
      role in hypocotyl cell elongation in Arabidopsis (Arabidopsis thaliana); this
      effect is mediated through PIF3. Ethylene signaling up-regulates MDP60 expression
      via PIF3 binding to the MDP60 promoter. MDP60 loss-of-function mutants exhibit
      much shorter hypocotyls, whereas MDP60 overexpression significantly promotes
      hypocotyl cell elongation when grown in light compared to the control. MDP60
      protein binds to microtubules in vitro and in vivo. The organization of cortical
      microtubules was significantly disrupted in mdp60 mutant cells and MDP60
      overexpressing seedlings. These findings indicate that MDP60 is an important
      mediator of hypocotyl cell elongation. This study reveals a mechanism in which
      light and ethylene signaling coordinate MDP60 expression to modulate hypocotyl
      cell elongation by altering cortical microtubules in Arabidopsis.

PMID- 29167355
TI  - Blood may buy goodwill: no evidence for a positive relationship between legal
      culling and poaching in Wisconsin.

PMID- 29167354
TI  - Advances in Imaging Plant Cell Dynamics.

PMID- 29167356
TI  - Flawed analysis and unconvincing interpretation: a comment on Chapron and Treves
      2016.

PMID- 29167357
TI  - How fish eggs are preadapted for the evolution of matrotrophy.
AB  - Teleost fishes evolved livebearing via egg retention 14 times. Matrotrophy has
      evolved within 12 of those lineages. By contrast, squamate reptiles evolved
      livebearing over 115 times, but only two to four of those lineages are known to
      have evolved matrotrophy. Is the discrepancy between these organisms in the
      probability of this transition caused by differences in their eggs? We show that
      the eggs of oviparous species in the superorder Atherinomorpha can acquire small
      organic molecules from their surrounding environment against a concentration
      gradient via mechanisms of active transport. Uptake rates were inhibited by
      competing radiolabelled amino acids against unlabelled versions of themselves.
      Transport was non-specific as uptake rates were similar for l-leucine and its
      biologically uncommon enantiomer d-leucine. Eggs are also capable of transporting
      larger microspheres across the membrane, but transport is inhibited at
      temperatures below 4 degrees C, suggesting active transport occurs via
      pinocytosis. Conflict theory predicts that the ability of the egg to acquire
      maternal resources will facilitate the embryo-parent arms race that leads to the
      evolution of matrotrophy following the transition to livebearing. The shelled
      eggs of amniotes lack such access to maternal resources when retained in the
      evolution of viviparity.

PMID- 29167358
TI  - Spatial memory shapes density dependence in population dynamics.
AB  - Most population dynamics studies assume that individuals use space uniformly, and
      thus mix well spatially. In numerous species, however, individuals do not move
      randomly, but use spatial memory to visit renewable resource patches repeatedly.
      To understand the extent to which memory-based foraging movement may affect
      density-dependent population dynamics through its impact on competition, we
      developed a spatially explicit, individual-based movement model where
      reproduction and death are functions of foraging efficiency. We compared the
      dynamics of populations of with- and without-memory individuals. We showed that
      memory-based movement leads to a higher population size at equilibrium, to a
      higher depletion of the environment, to a marked discrepancy between the global
      (i.e. measured at the population level) and local (i.e. measured at the
      individual level) intensities of competition, and to a nonlinear density
      dependence. These results call for a deeper investigation of the impact of
      individual movement strategies and cognitive abilities on population dynamics.

PMID- 29167359
TI  - Genome diversity in the Neolithic Globular Amphorae culture and the spread of
      Indo-European languages.
AB  - It is unclear whether Indo-European languages in Europe spread from the Pontic
      steppes in the late Neolithic, or from Anatolia in the Early Neolithic. Under the
      former hypothesis, people of the Globular Amphorae culture (GAC) would be
      descended from Eastern ancestors, likely representing the Yamnaya culture.
      However, nuclear (six individuals typed for 597 573 SNPs) and mitochondrial (11
      complete sequences) DNA from the GAC appear closer to those of earlier Neolithic
      groups than to the DNA of all other populations related to the Pontic steppe
      migration. Explicit comparisons of alternative demographic models via approximate
      Bayesian computation confirmed this pattern. These results are not in contrast to
      Late Neolithic gene flow from the Pontic steppes into Central Europe. However,
      they add nuance to this model, showing that the eastern affinities of the GAC in
      the archaeological record reflect cultural influences from other groups from the
      East, rather than the movement of people.

PMID- 29167360
TI  - The effect of climate change on the duration of avian breeding seasons: a meta
      analysis.
AB  - Many bird species are advancing the timing of their egg-laying in response to a
      warming climate. Little is known, however, of whether this advancement affects
      the respective length of the breeding seasons. A meta-analysis of 65 long-term
      studies of 54 species from the Northern Hemisphere has revealed that within the
      last 45 years an average population has lengthened the season by 1.4 days per
      decade, which was independent from changes in mean laying dates. Multi-brooded
      birds have prolonged their seasons by 4 days per decade, while single-brooded
      have shortened by 2 days. Changes in season lengths covaried with local climate
      changes: warming was correlated with prolonged seasons in multi-brooded species,
      but not in single-brooders. This might be a result of higher ecological
      flexibility of multi-brooded birds, whereas single brooders may have problems
      with synchronizing their reproduction with the peak of food resources. Sedentary
      species and short-distance migrants prolonged their breeding seasons more than
      long-distance migrants, which probably cannot track conditions at their breeding
      grounds. We conclude that as long as climate warming continues without major
      changes in ecological conditions, multi-brooded or sedentary species will
      probably increase their reproductive output, while the opposite effect may occur
      in single-brooded or migratory birds.

PMID- 29167361
TI  - Food-web dynamics under climate change.
AB  - Climate change affects ecological communities through its impact on the
      physiological performance of individuals. However, the population dynamic of
      species well inside their thermal niche is also determined by competitors, prey
      and predators, in addition to being influenced by temperature changes. We use a
      trait-based food-web model to examine how the interplay between the direct
      physiological effects from temperature and the indirect effects due to changing
      interactions between populations shapes the ecological consequences of climate
      change for populations and for entire communities. Our simulations illustrate how
      isolated communities deteriorate as populations go extinct when the environment
      moves outside the species' thermal niches. High-trophic-level species are most
      vulnerable, while the ecosystem function of lower trophic levels is less
      impacted. Open communities can compensate for the loss of ecosystem function by
      invasions of new species. Individual populations show complex responses largely
      uncorrelated with the direct impact of temperature change on physiology. Such
      complex responses are particularly evident during extinction and invasion events
      of other species, where climatically well-adapted species may be brought to
      extinction by the changed food-web topology. Our results highlight that the
      impact of climate change on specific populations is largely unpredictable, and
      apparently well-adapted species may be severely impacted.

PMID- 29167362
TI  - Reply to comments by Olson et al. 2017 and Stien 2017.

PMID- 29167363
TI  - Long-term archives reveal shifting extinction selectivity in China's postglacial
      mammal fauna.
AB  - Ecosystems have been modified by human activities for millennia, and insights
      about ecology and extinction risk based only on recent data are likely to be both
      incomplete and biased. We synthesize multiple long-term archives (over 250
      archaeological and palaeontological sites dating from the early Holocene to the
      Ming Dynasty and over 4400 historical records) to reconstruct the spatio-temporal
      dynamics of Holocene-modern range change across China, a megadiverse country
      experiencing extensive current-day biodiversity loss, for 34 mammal species over
      three successive postglacial time intervals. Our combined zooarchaeological,
      palaeontological, historical and current-day datasets reveal that both
      phylogenetic and spatial patterns of extinction selectivity have varied through
      time in China, probably in response both to cumulative anthropogenic impacts (an
      'extinction filter' associated with vulnerable species and accessible landscapes
      being affected earlier by human activities) and also to quantitative and
      qualitative changes in regional pressures. China has experienced few postglacial
      global species-level mammal extinctions, and most species retain over 50% of
      their maximum estimated Holocene range despite millennia of increasing regional
      human pressures, suggesting that the potential still exists for successful
      species conservation and ecosystem restoration. Data from long-term archives also
      demonstrate that herbivores have experienced more historical extinctions in
      China, and carnivores have until recently displayed greater resilience. Accurate
      assessment of patterns of biodiversity loss and the likely predictive power of
      current-day correlates of faunal vulnerability and resilience is dependent upon
      novel perspectives provided by long-term archives.

PMID- 29167364
TI  - Fear of predation shapes social network structure and the acquisition of foraging
      information in guppy shoals.
AB  - Spatio-temporal variation in predation risk is predicted to select for plastic
      anti-predator responses, which may in turn impact the fine-scale social structure
      of prey groups and processes mediated by that structure. To test these
      predictions, we manipulated the ambient predation risk experienced by Trinidadian
      guppy (Poecilia reticulata) groups before quantifying their social networks and
      recording individual latencies to approach and solve a novel foraging task. High
      risk conditions drove the formation of social networks that were more strongly
      assorted by body size than those exposed to low ambient risk and promoted longer
      durations of contact between preferred partners. Additionally, high background
      predation risk reduced the probability individuals would approach and solve a
      novel foraging task. Network-based diffusion analysis revealed that while social
      transmission of the task solution from knowledgeable to naive individuals
      occurred at a higher rate within low-risk groups, individuals in high-risk groups
      were particularly likely to investigate the task while shoaling with preferred
      social partners. Taken together, our results suggest that the structure and
      functional importance of prey social networks may partly depend on local
      predation pressure. Furthermore, by influencing individuals' access to
      information, fear of predation may impact decision-making in a potentially wide
      array of behavioural contexts.

PMID- 29167365
TI  - Correlated individual differences suggest a common mechanism underlying
      metacognition in visual perception and visual short-term memory.
AB  - Adaptive behaviour depends on the ability to introspect accurately about one's
      own performance. Whether this metacognitive ability is supported by the same
      mechanisms across different tasks is unclear. We investigated the relationship
      between metacognition of visual perception and metacognition of visual short-term
      memory (VSTM). Experiments 1 and 2 required subjects to estimate the perceived or
      remembered orientation of a grating stimulus and rate their confidence. We
      observed strong positive correlations between individual differences in
      metacognitive accuracy between the two tasks. This relationship was not accounted
      for by individual differences in task performance or average confidence, and was
      present across two different metrics of metacognition and in both experiments. A
      model-based analysis of data from a third experiment showed that a cross-domain
      correlation only emerged when both tasks shared the same task-relevant stimulus
      feature. That is, metacognition for perception and VSTM were correlated when both
      tasks required orientation judgements, but not when the perceptual task was
      switched to require contrast judgements. In contrast with previous results
      comparing perception and long-term memory, which have largely provided evidence
      for domain-specific metacognitive processes, the current findings suggest that
      metacognition of visual perception and VSTM is supported by a domain-general
      metacognitive architecture, but only when both domains share the same task
      relevant stimulus feature.

PMID- 29167367
TI  - Embryonic origin of the gnathostome vertebral skeleton.
AB  - The vertebral column is a key component of the jawed vertebrate (gnathostome)
      body plan, but the primitive embryonic origin of this skeleton remains unclear.
      In tetrapods, all vertebral components (neural arches, haemal arches and centra)
      derive from paraxial mesoderm (somites). However, in teleost fishes, vertebrae
      have a dual embryonic origin, with arches derived from somites, but centra
      formed, in part, by secretion of bone matrix from the notochord. Here, we test
      the embryonic origin of the vertebral skeleton in a cartilaginous fish (the
      skate, Leucoraja erinacea) which serves as an outgroup to tetrapods and teleosts.
      We demonstrate, by cell lineage tracing, that both arches and centra are somite
      derived. We find no evidence of cellular or matrix contribution from the
      notochord to the skate vertebral skeleton. These findings indicate that the
      earliest gnathostome vertebral skeleton was exclusively of somitic origin, with a
      notochord contribution arising secondarily in teleosts.

PMID- 29167366
TI  - Archaeogenomic analysis of the first steps of Neolithization in Anatolia and the
      Aegean.
AB  - The Neolithic transition in west Eurasia occurred in two main steps: the gradual
      development of sedentism and plant cultivation in the Near East and the
      subsequent spread of Neolithic cultures into the Aegean and across Europe after
      7000 cal BCE. Here, we use published ancient genomes to investigate gene flow
      events in west Eurasia during the Neolithic transition. We confirm that the Early
      Neolithic central Anatolians in the ninth millennium BCE were probably
      descendants of local hunter-gatherers, rather than immigrants from the Levant or
      Iran. We further study the emergence of post-7000 cal BCE north Aegean Neolithic
      communities. Although Aegean farmers have frequently been assumed to be colonists
      originating from either central Anatolia or from the Levant, our findings raise
      alternative possibilities: north Aegean Neolithic populations may have been the
      product of multiple westward migrations, including south Anatolian emigrants, or
      they may have been descendants of local Aegean Mesolithic groups who adopted
      farming. These scenarios are consistent with the diversity of material cultures
      among Aegean Neolithic communities and the inheritance of local forager know-how.
      The demographic and cultural dynamics behind the earliest spread of Neolithic
      culture in the Aegean could therefore be distinct from the subsequent
      Neolithization of mainland Europe.

PMID- 29167368
TI  - Perception of contextual size illusions by honeybees in restricted and
      unrestricted viewing conditions.
AB  - How different visual systems process images and make perceptual errors can inform
      us about cognitive and visual processes. One of the strongest geometric errors in
      perception is a misperception of size depending on the size of surrounding
      objects, known as the Ebbinghaus or Titchener illusion. The ability to perceive
      the Ebbinghaus illusion appears to vary dramatically among vertebrate species,
      and even populations, but this may depend on whether the viewing distance is
      restricted. We tested whether honeybees perceive contextual size illusions, and
      whether errors in perception of size differed under restricted and unrestricted
      viewing conditions. When the viewing distance was unrestricted, there was an
      effect of context on size perception and thus, similar to humans, honeybees
      perceived contrast size illusions. However, when the viewing distance was
      restricted, bees were able to judge absolute size accurately and did not succumb
      to visual illusions, despite differing contextual information. Our results show
      that accurate size perception depends on viewing conditions, and thus may explain
      the wide variation in previously reported findings across species. These results
      provide insight into the evolution of visual mechanisms across vertebrate and
      invertebrate taxa, and suggest convergent evolution of a visual processing
      solution.

PMID- 29167369
TI  - Correction to 'Deceptive vocal duets and multi-modal display in a songbird'.

PMID- 29167370
TI  - Uncertainty, epistemics and active inference.
AB  - Biological systems-like ourselves-are constantly faced with uncertainty. Despite
      noisy sensory data, and volatile environments, creatures appear to actively
      maintain their integrity. To account for this remarkable ability to make optimal
      decisions in the face of a capricious world, we propose a generative model that
      represents the beliefs an agent might possess about their own uncertainty. By
      simulating a noisy and volatile environment, we demonstrate how uncertainty
      influences optimal epistemic (visual) foraging. In our simulations, saccades were
      deployed less frequently to regions with a lower sensory precision, while a
      greater volatility led to a shorter inhibition of return. These simulations
      illustrate a principled explanation for some cardinal aspects of visual foraging
      and allow us to propose a correspondence between the representation of
      uncertainty and ascending neuromodulatory systems, complementing that suggested
      by Yu & Dayan (Yu & Dayan 2005 Neuron46, 681-692.
      (doi:10.1016/j.neuron.2005.04.026)).

PMID- 29167371
TI  - Spontaneous oscillations of elastic filaments induced by molecular motors.
AB  - It is known from the wave-like motion of microtubules in motility assays that the
      piconewton forces that motors produce can be sufficient to bend the filaments. In
      cellular phenomena such as cytosplasmic streaming, molecular motors translocate
      along cytoskeletal filaments, carrying cargo which entrains fluid. When large
      numbers of such forced filaments interact through the surrounding fluid, as in
      particular stages of oocyte development in Drosophila melanogaster, complex
      dynamics are observed, but the detailed mechanics underlying them has remained
      unclear. Motivated by these observations, we study here perhaps the simplest
      model for these phenomena: an elastic filament, pinned at one end, acted on by a
      molecular motor treated as a point force. Because the force acts tangential to
      the filament, no matter what its shape, this 'follower-force' problem is
      intrinsically non-variational, and thereby differs fundamentally from Euler
      buckling, where the force has a fixed direction, and which, in the low-Reynolds
      number regime, ultimately leads to a stationary, energy-minimizing shape. Through
      a combination of linear stability theory, analytical study of a solvable
      simplified 'two-link' model and numerical studies of the full elastohydrodynamic
      equations of motion, we elucidate the Hopf bifurcation that occurs with
      increasing forcing of a filament, leading to flapping motion analogous to the
      high-Reynolds-number oscillations of a garden hose with a free end.

PMID- 29167372
TI  - Effects of spanwise flexibility on the performance of flapping flyers in forward
      flight.
AB  - Flying animals possess flexible wings that deform during flight. The chordwise
      flexibility alters the wing shape, affecting the effective angle of attack and
      hence the surrounding aerodynamics. However, the effects of spanwise flexibility
      on the locomotion are inadequately understood. Here, we present a two-way coupled
      aeroelastic model of a plunging spanwise flexible wing. The aerodynamics is
      modelled with a two-dimensional, unsteady, incompressible potential flow model,
      evaluated at each spanwise location of the wing. The two-way coupling is realized
      by considering the transverse displacement as the effective plunge under the
      dynamic balance of wing inertia, elastic restoring force and aerodynamic force.
      The thrust is a result of the competition between the enhancement due to wing
      deformation and induced drag. The results for a purely plunging spanwise flexible
      wing agree well with experimental and high-fidelity numerical results from the
      literature. Our analysis suggests that the wing aspect ratio of the abstracted
      passerine and goose models corresponds to the optimal aeroelastic response,
      generating the highest thrust while minimizing the power required to flap the
      wings. At these optimal aspect ratios, the flapping frequency is near the first
      spanwise natural frequency of the wing, suggesting that these birds may benefit
      from the resonance to generate thrust.

PMID- 29167373
TI  - Epitranscriptomic profiling across cell types reveals associations between
      APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function.
AB  - Epitranscriptomics refers to posttranscriptional alterations on an mRNA sequence
      that are dynamic and reproducible, and affect gene expression in a similar way to
      epigenetic modifications. However, the functional relevance of those
      modifications for the transcript, the cell, and the organism remain poorly
      understood. Here, we focus on RNA editing and show that Apolipoprotein B mRNA
      editing enzyme, catalytic polypeptide-1 (APOBEC1), together with its cofactor
      RBM47, mediates robust editing in different tissues. The majority of editing
      events alter the sequence of the 3'UTR of targeted transcripts, and we focus on
      one cell type (monocytes) and on a small set of highly edited transcripts within
      it to show that editing alters gene expression by modulating translation (but not
      RNA stability or localization). We further show that specific cellular processes
      (phagocytosis and transendothelial migration) are enriched for transcripts that
      are targets of editing and that editing alters their function. Finally, we survey
      bone marrow progenitors and demonstrate that common monocyte progenitor cells
      express high levels of APOBEC1 and are susceptible to loss of the editing enzyme.
      Overall, APOBEC1-mediated transcriptome diversification is required for the fine
      tuning of protein expression in monocytes, suggesting an epitranscriptomic
      mechanism for the proper maintenance of homeostasis in innate immune cells.

PMID- 29167374
TI  - FMRFamide-like peptides expand the behavioral repertoire of a densely connected
      nervous system.
AB  - Animals, including humans, can adapt to environmental stress through phenotypic
      plasticity. The free-living nematode Caenorhabditis elegans can adapt to harsh
      environments by undergoing a whole-animal change, involving exiting reproductive
      development and entering the stress-resistant dauer larval stage. The dauer is a
      dispersal stage with dauer-specific behaviors for finding and stowing onto
      carrier animals, but how dauers acquire these behaviors, despite having a
      physically limited nervous system of 302 neurons, is poorly understood. We
      compared dauer and reproductive development using whole-animal RNA sequencing at
      fine time points and at sufficient depth to measure transcriptional changes
      within single cells. We detected 8,042 genes differentially expressed during
      dauer and reproductive development and observed striking up-regulation of
      neuropeptide genes during dauer entry. We knocked down neuropeptide processing
      using sbt-1 mutants and demonstrate that neuropeptide signaling promotes the
      decision to enter dauer rather than reproductive development. We also demonstrate
      that during dauer neuropeptides modulate the dauer-specific nictation behavior
      (carrier animal-hitchhiking) and are necessary for switching from repulsion to
      CO2 (a carrier animal cue) in nondauers to CO2 attraction in dauers. We tested
      individual neuropeptides using CRISPR knockouts and existing strains and
      demonstrate that the combined effects of flp-10 and flp-17 mimic the effects of
      sbt-1 on nictation and CO2 attraction. Through meta-analysis, we discovered
      similar up-regulation of neuropeptides in the dauer-like infective juveniles of
      diverse parasitic nematodes, suggesting the antiparasitic target potential of SBT
      1. Our findings reveal that, under stress, increased neuropeptide signaling in C.
      elegans enhances their decision-making accuracy and expands their behavioral
      repertoire.

PMID- 29167376
TI  - 4-Valent Human Papillomavirus (4vHPV) Vaccine in Preadolescents and Adolescents
      After 10 Years.
AB  - OBJECTIVES: We describe the final 10-year data for the long-term follow-up study
      of the 4-valent human papillomavirus (4vHPV) vaccine in preadolescents and
      adolescents. METHODS: In the base study (V501-018), 1661 sexually inactive boys
      and girls received the 4vHPV vaccine (early vaccination group [EVG], managed for
      9.9 years) or a placebo at day 1, month 2, and month 6. Thereafter, at month 30,
      the placebo group (catch-up vaccination group [CVG], managed for 7.4 years)
      received the 4vHPV vaccine by using the same dosing schedule. Long-term anti-HPV
      type 6, 11, 16, and 18 immune responses were assessed. Effectiveness was
      estimated by calculating the incidence rate of the primary endpoints (HPV types
      6, 11, 16, and 18-related disease or persistent infection). RESULTS: For HPV
      types 6, 11, and 16, 89% to 96% of subjects remained seropositive through 10
      years postvaccination. The preadolescents had 38% to 65% higher geometric mean
      titers at month 7, which remained 16% to 42% higher at 10 years compared with
      adolescents. No cases of HPV type 6, 11, 16, and 18-related diseases were
      observed. Ten subjects had a persistent infection of >=6 months duration with
      vaccine-type HPV and 2 subjects had persistent infection for >=12 months. No new
      serious adverse events were reported through 10 years. CONCLUSIONS: A 3-dose
      regimen of the 4vHPV vaccine was immunogenic, clinically effective, and generally
      well tolerated in preadolescents and adolescents during 10 years of follow-up.
      These long-term findings support efforts to vaccinate this population against HPV
      before exposure.

PMID- 29167375
TI  - Loss of APOBEC1 RNA-editing function in microglia exacerbates age-related CNS
      pathophysiology.
AB  - Microglia (MG), a heterogeneous population of phagocytic cells, play important
      roles in central nervous system (CNS) homeostasis and neural plasticity. Under
      steady-state conditions, MG maintain homeostasis by producing antiinflammatory
      cytokines and neurotrophic factors, support myelin production, and remove
      synapses and cellular debris, as well as participating in "cross-correction," a
      process that supplies neurons with key factors for executing autophagy-lysosomal
      function. As sentinels for the immune system, MG also detect "danger" signals
      (pathogenic or traumatic insult), become activated, produce proinflammatory
      cytokines, and recruit monocytes and dendritic cells to the site of damage
      through a breached blood-brain barrier or via brain lymphatics. Failure to
      effectively resolve MG activation can be problematic and can lead to chronic
      inflammation, a condition proposed to underlie CNS pathophysiology in heritable
      brain disorders and age-related neurodegenerative and cognitive decline. Here, we
      show that APOBEC1-mediated RNA editing occurs within MG and is key to maintaining
      their resting status. Like bone marrow-derived macrophages, RNA editing in MG
      leads to overall changes in the abundance of edited proteins that coordinate the
      function of multiple cellular pathways. Conversely, mice lacking the APOBEC1
      editing function in MG display evidence of dysregulation, with progressive age
      related signs of neurodegeneration, characterized by clustering of activated MG,
      aberrant myelination, increased inflammation, and lysosomal anomalies that
      culminate in behavioral and motor deficiencies. Collectively, our study
      identifies posttranscriptional modification by RNA editing as a critical
      regulatory mechanism of vital cellular functions that maintain overall brain
      health.

PMID- 29167377
TI  - Oropharyngeal Dysphagia and Cerebral Palsy.
AB  - OBJECTIVES: To determine the progression of oropharyngeal dysphagia (OPD) in
      preschool-aged children with cerebral palsy (CP) according to gross motor
      function. It was hypothesized that fewer children would have OPD at 60 months
      compared with 18 to 24 months (predominately Gross Motor Function Classification
      System [GMFCS] I-II). METHODS: Longitudinal population-based cohort of 179
      children (confirmed CP diagnosis, born in Queensland in 2006-2009, aged 18-60
      months at study entry [mean = 34.1 months +/- 11.9; 111 boys; GMFCS I = 46.6%, II
      = 12.9%, III = 15.7%, IV = 10.1%, and V = 14.6%]). Children had a maximum of 3
      assessments (median = 3, total n = 423 assessments). OPD was classified by using
      the Dysphagia Disorders Survey part 2 and rated from video by a certified
      pediatric speech pathologist. GMFCS was used to classify children's gross motor
      function. RESULTS: OPD prevalence reduced from 79.7% at 18 to 24 months to 43.5%
      at 60 months. There were decreasing odds of OPD with increasing age (odds ratio
      [OR] = 0.92 [95% confidence interval (CI) 0.90 to 0.95]; P < .001) and increasing
      odds with poorer gross motor function (OR = 6.2 [95% CI 3.6 to 10.6]; P < .001).
      This reduction was significant for children with ambulatory CP (GMFCS I-II, OR =
      0.93 [95% CI 0.90 to 0.96]; P < .001) but not significant for children from GMFCS
      III to V (OR [III] = 1.0 [95% CI 0.9 to 1.1]; P = .897; OR [IV-V] = 1.0 [95% CI
      1.0 to 1.1]; P = .366). CONCLUSIONS: Half of the OPD present in children with CP
      between 18 and 24 months resolved by 60 months, with improvement most common in
      GMFCS I to II. To more accurately detect and target intervention at children with
      persisting OPD at 60 months, we suggest using a more conservative cut point of 6
      out of 22 on the Dysphagia Disorders Survey for assessments between 18 and 48
      months.

PMID- 29167378
TI  - Momentary Parental Stress and Food-Related Parenting Practices.
AB  - BACKGROUND: Research suggests that stress and depressed mood are associated with
      food-related parenting practices (ie, parent feeding practices, types of food
      served at meals). However, current measures of parental stress, depressed mood,
      and food-related parenting practices are typically survey-based and assessed as
      static/unchanging characteristics, failing to account for fluctuations across
      time and context. Identifying momentary factors that influence parent food
      related parenting practices will facilitate the development of effective
      interventions aimed at promoting healthy food-related parenting practices. In
      this study, we used ecological momentary assessment to examine the association
      between momentary factors (eg, stress, depressed mood) occurring early in the day
      and food-related parenting practices at the evening meal. METHODS: Children aged
      5 to 7 years and their families (N = 150) from 6 racial and/or ethnic groups (n =
      25 each African American, Hispanic/Latino, Hmong, American Indian, Somali, and
      white families) were recruited for this mixed-methods study through primary care
      clinics. RESULTS: Higher stress and depressed mood earlier in the day predicted
      pressure-to-eat feeding practices and fewer homemade foods served at meals the
      same night. Effect modification was found for certain racial and/or ethnic groups
      with regard to engaging in pressure-to-eat feeding practices (ie, America Indian,
      Somali) or serving fewer homemade meals (ie, African American, Hispanic/Latino)
      in the face of high stress or depressed mood. CONCLUSIONS: Clinicians may want to
      consider discussing with parents the influence stress and depressed mood can have
      on everyday food-related parenting practices. Additionally, future researchers
      should consider using real-time interventions to reduce parental stress and
      depressed mood to promote healthy parent food-related parenting practices.

PMID- 29167379
TI  - Tau can switch microtubule network organizations: from random networks to dynamic
      and stable bundles.
AB  - In neurons, microtubule networks alternate between single filaments and bundled
      arrays under the influence of effectors controlling their dynamics and
      organization. Tau is a microtubule bundler that stabilizes microtubules by
      stimulating growth and inhibiting shrinkage. The mechanisms by which tau
      organizes microtubule networks remain poorly understood. Here, we studied the
      self-organization of microtubules growing in the presence of tau isoforms and
      mutants. The results show that tau's ability to induce stable microtubule bundles
      requires two hexapeptides located in its microtubule-binding domain and is
      modulated by its projection domain. Site-specific pseudophosphorylation of tau
      promotes distinct microtubule organizations: stable single microtubules, stable
      bundles, or dynamic bundles. Disease-related tau mutations increase the formation
      of highly dynamic bundles. Finally, cryo-electron microscopy experiments indicate
      that tau and its variants similarly change the microtubule lattice structure by
      increasing both the protofilament number and lattice defects. Overall, our
      results uncover novel phosphodependent mechanisms governing tau's ability to
      trigger microtubule organization and reveal that disease-related modifications of
      tau promote specific microtubule organizations that may have a deleterious impact
      during neurodegeneration.

PMID- 29167381
TI  - CRISPR-Trap: a clean approach for the generation of gene knockouts and gene
      replacements in human cells.
AB  - CRISPR/Cas9-based genome editing offers the possibility to knock out almost any
      gene of interest in an affordable and simple manner. The most common strategy is
      the introduction of a frameshift into the open reading frame (ORF) of the target
      gene which truncates the coding sequence (CDS) and targets the corresponding
      transcript for degradation by nonsense-mediated mRNA decay (NMD). However, we
      show that transcripts containing premature termination codons (PTCs) are not
      always degraded efficiently and can generate C-terminally truncated proteins
      which might have residual or dominant negative functions. Therefore, we recommend
      an alternative approach for knocking out genes, which combines CRISPR/Cas9 with
      gene traps (CRISPR-Trap) and is applicable to ~50% of all spliced human protein
      coding genes and a large subset of lncRNAs. CRISPR-Trap completely prevents the
      expression of the ORF and avoids expression of C-terminal truncated proteins. We
      demonstrate the feasibility of CRISPR-Trap by utilizing it to knock out several
      genes in different human cell lines. Finally, we also show that this approach can
      be used to efficiently generate gene replacements allowing for modulation of
      protein levels for otherwise lethal knockouts (KOs). Thus, CRISPR-Trap offers
      several advantages over conventional KO approaches and allows for generation of
      clean CRISPR/Cas9-based KOs.

PMID- 29167380
TI  - Self-oligomerization regulates stability of survival motor neuron protein
      isoforms by sequestering an SCFSlmb degron.
AB  - Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1
      Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and
      production of an unstable protein isoform, SMNDelta7. Although SMN2 exon skipping
      is the principal contributor to SMA severity, mechanisms governing stability of
      survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila
      model system and label-free proteomics to identify the SCFSlmb ubiquitin E3
      ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor
      degron embedded within the human and fruitfly SMN YG-box oligomerization domains.
      Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and
      stabilizes SMNDelta7. SMA-causing missense mutations that block multimerization
      of full-length SMN are also stabilized in the degron mutant background.
      Overexpression of SMNDelta7S270A, but not wild-type (WT) SMNDelta7, provides a
      protective effect in SMA model mice and human motor neuron cell culture systems.
      Our findings support a model wherein the degron is exposed when SMN is monomeric
      and sequestered when SMN forms higher-order multimers.

PMID- 29167382
TI  - Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely
      abscission in human cells.
AB  - Cytokinesis requires the cooperation of many cytoskeletal and membrane
      regulators. Most of the major players required for cytokinesis are known, but the
      temporal regulation and adaptations for different cell types are less understood.
      KIF20B (previously called MPHOSPH1 or MPP1) is a member of the Kinesin-6 family,
      which also includes the better-known members KIF23/MKLP1 and KIF20A/MKLP2.
      Previously, we showed that mouse Kif20b is involved in cerebral cortex growth and
      midbody organization of neural stem cells. Here, using siRNA-mediated knockdown
      of KIF20B in a human cell line and fixed and live imaging, we show that KIF20B
      has a cell-autonomous role in cytokinesis. KIF20B depletion affects the speed of
      both furrow ingression and abscission. It localizes to microtubules of the
      central spindle and midbody throughout cytokinesis, at sites distinct from the
      other Kinesin-6 family members. KIF20B is not required for midbody assembly, but
      may accelerate or coordinate midbody maturation. In particular, KIF20B appears to
      regulate late steps of maturation including anillin dispersal, ESCRT-III
      recruitment, and the formation of microtubule constriction sites.

PMID- 29167383
TI  - C-terminal Src kinase (Csk) regulates the tricellular junction protein Gliotactin
      independent of Src.
AB  - Tricellular junctions (TCJs) are uniquely placed permeability barriers formed at
      the corners of polarized epithelia where tight junctions in vertebrates or
      septate junctions (SJ) in invertebrates from three cells converge. Gliotactin is
      a Drosophila TCJ protein, and loss of Gliotactin results in SJ and TCJ breakdown
      and permeability barrier loss. When overexpressed, Gliotactin spreads away from
      the TCJs, resulting in disrupted epithelial architecture, including
      overproliferation, cell delamination, and migration. Gliotactin levels are
      tightly controlled at the mRNA level and at the protein level through endocytosis
      and degradation triggered by tyrosine phosphorylation. We identified C-terminal
      Src kinase (Csk) as a tyrosine kinase responsible for regulating Gliotactin
      endocytosis. Increased Csk suppresses the Gliotactin overexpression phenotypes by
      increasing endocytosis. Loss of Csk causes Gliotactin to spread away from the
      TCJ. Although Csk is known as a negative regulator of Src kinases, the effects of
      Csk on Gliotactin are independent of Src and likely occur through an adherens
      junction associated complex. Overall, we identified a new Src-independent role
      for Csk in the control of Gliotactin, a key tricellular junction protein.

PMID- 29167385
TI  - Do Intracerebral Hemorrhage Nonexpanders Actually Expand Into the Ventricular
      Space?
AB  - BACKGROUND AND PURPOSE: The computed tomographic angiography spot sign as a
      predictor of hematoma expansion is limited by its modest sensitivity and positive
      predictive value. It is possible that hematoma expansion in spot-positive
      patients is missed because of decompression of intracerebral hemorrhage (ICH)
      into the ventricular space. We hypothesized that revising hematoma expansion
      definitions to include intraventricular hemorrhage (IVH) expansion will improve
      the predictive performance of the spot sign. Our objectives were to determine the
      proportion of ICH nonexpanders who actually have IVH expansion, determine the
      proportion of false-positive spot signs that have IVH expansion, and compare the
      known predictive performance of the spot sign to a revised definition
      incorporating IVH expansion. METHODS: We analyzed patients from the multicenter
      PREDICT ICH spot sign study. We defined hematoma expansion as >=6 mL or >=33% ICH
      expansion or >2 mL IVH expansion and compared spot sign performance using this
      revised definition with the conventional 6 mL/33% definition using receiver
      operating curve analysis. RESULTS: Of 311 patients, 213 did not meet the 6-mL/33%
      expansion definition (nonexpanders). Only 13 of 213 (6.1%) nonexpanders had >=2
      mL IVH expansion. Of the false-positive spot signs, 4 of 40 (10%) had >2 mL
      ventricular expansion. The area under the curve for spot sign to predict
      significant ICH expansion was 0.65 (95% confidence interval, 0.58-0.72), which
      was no different than when IVH expansion was added to the definition (area under
      the curve, 0.66; 95% confidence interval, 0.58-0.71). CONCLUSIONS: Although IVH
      expansion does indeed occur in a minority of ICH nonexpanders, its inclusion into
      a revised hematoma expansion definition does not alter the predictive performance
      of the spot sign.

PMID- 29167384
TI  - DRC2/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex
      and other regulators of ciliary and flagellar motility.
AB  - The nexin-dynein regulatory complex (N-DRC) plays a central role in the
      regulation of ciliary and flagellar motility. In most species, the N-DRC contains
      at least 11 subunits, but the specific function of each subunit is unknown.
      Mutations in three subunits (DRC1, DRC2/CCDC65, DRC4/GAS8) have been linked to
      defects in ciliary motility in humans and lead to a ciliopathy known as primary
      ciliary dyskinesia (PCD). Here we characterize the biochemical, structural, and
      motility phenotypes of two mutations in the DRC2 gene of Chlamydomonas Using high
      resolution proteomic and structural approaches, we find that the C-terminal
      region of DRC2 is critical for the coassembly of DRC2 and DRC1 to form the base
      plate of N-DRC and its attachment to the outer doublet microtubule. Loss of DRC2
      in drc2 mutants disrupts the assembly of several other N-DRC subunits and also
      destabilizes the assembly of several closely associated structures such as the
      inner dynein arms, the radial spokes, and the calmodulin- and spoke-associated
      complex. Our study provides new insights into the range of ciliary defects that
      can lead to PCD.

PMID- 29167386
TI  - Ischemic Stroke Profile, Risk Factors, and Outcomes in India: The Indo-US
      Collaborative Stroke Project.
AB  - BACKGROUND AND PURPOSE: The Indo-US Collaborative Stroke Project was designed to
      characterize ischemic stroke across 5 high-volume academic tertiary hospitals in
      India. METHODS: From January 2012 to August 2014, research coordinators and
      physician coinvestigators prospectively collected data on 2066 patients with
      ischemic stroke admitted <2 weeks after onset. Investigator training and
      supervision and data monitoring were conducted by the US site (Massachusetts
      General Hospital, Boston). RESULTS: The mean age was 58.3+/-14.7 years, 67.2%
      men. The median admission National Institutes of Health Stroke Scale score was 10
      (interquartile range, 5-15) and 24.5% had National Institutes of Health Stroke
      Scale >=16. Hypertension (60.8%), diabetes mellitus (35.7%), and tobacco use
      (32.2%, including bidi/smokeless tobacco) were common risk factors. Only 4% had
      atrial fibrillation. All patients underwent computed tomography or magnetic
      resonance imaging; 81% had cerebrovascular imaging. Stroke etiologic subtypes
      were large artery (29.9%), cardiac (24.9%), small artery (14.2%), other definite
      (3.4%), and undetermined (27.6%, including 6.7% with incomplete evaluation).
      Intravenous or intra-arterial thrombolysis was administered in 13%. In-hospital
      mortality was 7.9%, and 48% achieved modified Rankin Scale score 0 to 2 at 90
      days. On multivariate analysis, diabetes mellitus predicted poor 3-month outcome
      and younger age, lower admission National Institutes of Health Stroke Scale and
      small-artery etiology predicted excellent 3-month outcome. CONCLUSIONS: These
      comprehensive and novel clinical imaging data will prove useful in refining
      stroke guidelines and advancing stroke care in India.

PMID- 29167387
TI  - Prehospital Systolic Blood Pressure Is Related to Intracerebral Hemorrhage Volume
      on Admission.
AB  - BACKGROUND AND PURPOSE: Ultra-early blood pressure (BP) management in the
      prehospital setting could improve the efficacy of this treatment on attenuating
      intracerebral hemorrhage (ICH) expansion. We aimed to determine the association
      of prehospital systolic BP (SBP) with ICH volume, ultra-early hematoma growth,
      and the spot sign on admission. METHODS: We conducted a retrospective study of a
      prospective database of 219 consecutive patients with spontaneous ICH admitted to
      the emergency department of a tertiary stroke center during a 3-year period.
      Prehospital SBP and ICH volume, ultra-early hematoma growth (ICH volume/onset-to
      imaging time), and presence of the spot sign on admission were prospectively
      recorded. Primary outcome was ICH volume on admission. Secondary outcomes
      included ultra-early hematoma growth and frequency of the spot sign in patients
      scanned within 6 hours from symptom onset (hyperacute group). RESULTS:
      Prehospital SBP was positively correlated with both SBP (r=0.552; P<0.001) and
      ICH volume (rho=0.189; P=0.006) on admission. Patients with ICH volume above the
      median value presented higher prehospital SBP (172.3+/-35.0 versus 163.7+/-27.8
      mm Hg; P=0.049). This association remained significant in adjusted multiple
      logistic regression analysis (odds ratio, 1.01 for a 1-U increase in SBP; 95%
      confidence interval, 1.01-1.02; P=0.018). In the hyperacute group (n=126),
      prehospital SBP was unrelated to ultra-early hematoma growth (rho=0.115; P=0.203)
      nor the presence of the spot sign (172.2+/-27.6 versus 171.8+/-31.6 mm Hg;
      P=0.959). CONCLUSIONS: Prehospital SBP is correlated with SBP on admission and
      independently associated with ICH volume on admission. These findings support the
      rationale of testing whether prehospital initiation of BP-lowering attenuates ICH
      expansion.

PMID- 29167388
TI  - Real-World Use of Apixaban for Stroke Prevention in Atrial Fibrillation: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: The use of oral anticoagulant therapy for stroke
      prevention in atrial fibrillation has been transformed by the availability of the
      nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of
      nonvitamin K antagonist oral anticoagulants would help elucidate their
      effectiveness and safety in daily clinical practice. Apixaban was the third
      nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and
      increasing real-world studies have been published. Our aim was to summarize
      current evidence about real-world studies on apixaban for stroke prevention in
      atrial fibrillation. METHODS: We performed a systematic review and meta-analysis
      of all observational real-world studies comparing apixaban with other available
      oral anticoagulant drugs. RESULTS: From the original 9680 results retrieved, 16
      studies have been included in the final meta-analysis. Compared with warfarin,
      apixaban regular dose was more effective in reducing any thromboembolic event
      (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant
      difference was found for stroke risk. Apixaban was as effective as dabigatran and
      rivaroxaban in reducing thromboembolic events and stroke. The risk of major
      bleeding was significantly lower for apixaban compared with warfarin, dabigatran,
      and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively).
      Similarly, the risk for intracranial hemorrhage was significantly lower for
      apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not
      dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when
      compared with all oral anticoagulant agents (P<0.00001 for all comparisons).
      CONCLUSIONS: Use of apixaban in real-life is associated with an overall similar
      effectiveness in reducing stroke and any thromboembolic events when compared with
      warfarin. A better safety profile was found with apixaban compared with warfarin,
      dabigatran, and rivaroxaban.

PMID- 29167389
TI  - Symptomatic Intracranial Atherosclerosis With Impaired Distal Perfusion: A Case
      Study.

PMID- 29167390
TI  - Early Elevated Troponin Levels After Ischemic Stroke Suggests a Cardioembolic
      Source.
AB  - BACKGROUND AND PURPOSE: Elevated cardiac troponin is a marker of cardiac disease
      and has been recently shown to be associated with embolic stroke risk. We
      hypothesize that early elevated troponin levels in the acute stroke setting are
      more prevalent in patients with embolic stroke subtypes (cardioembolic and
      embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large
      vessel disease, small-vessel disease, and other). METHODS: We abstracted data
      from our prospective ischemic stroke database and included all patients with
      ischemic stroke during an 18-month period. Per our laboratory, we defined
      positive troponin as >=0.1 ng/mL and intermediate as >=0.06 ng/mL and <0.1 ng/mL.
      Unadjusted and adjusted regression models were built to determine the association
      between stroke subtype (embolic stroke of unknown source and cardioembolic
      subtypes) and positive and intermediate troponin levels, adjusting for key
      confounders, including demographics (age and sex), clinical characteristics
      (hypertension, hyperlipidemia, diabetes mellitus, renal function, coronary heart
      disease, congestive heart failure, current smoking, and National Institutes of
      Health Stroke Scale score), cardiac variables (left atrial diameter, wall-motion
      abnormalities, ejection fraction, and PR interval on ECG), and insular
      involvement of infarct. RESULTS: We identified 1234 patients, of whom 1129 had
      admission troponin levels available; 10.0% (113/1129) of these had a positive
      troponin. In fully adjusted models, there was an association between troponin
      positivity and embolic stroke of unknown source subtype (adjusted odds ratio,
      4.46; 95% confidence interval, 1.03-7.97; P=0.003) and cardioembolic stroke
      subtype (odds ratio, 5.00; 95% confidence interval, 1.83-13.63; P=0.002).
      CONCLUSIONS: We found that early positive troponin after ischemic stroke may be
      independently associated with a cardiac embolic source. Future studies are needed
      to confirm our findings using high-sensitivity troponin assays and to test
      optimal secondary prevention strategies in patients with embolic stroke of
      unknown source and positive troponin.

PMID- 29167391
TI  - Integrated genomic and interfacility patient-transfer data reveal the
      transmission pathways of multidrug-resistant Klebsiella pneumoniae in a regional
      outbreak.
AB  - Development of effective strategies to limit the proliferation of multidrug
      resistant organisms requires a thorough understanding of how such organisms
      spread among health care facilities. We sought to uncover the chains of
      transmission underlying a 2008 U.S. regional outbreak of carbapenem-resistant
      Klebsiella pneumoniae by performing an integrated analysis of genomic and
      interfacility patient-transfer data. Genomic analysis yielded a high-resolution
      transmission network that assigned directionality to regional transmission events
      and discriminated between intra- and interfacility transmission when
      epidemiologic data were ambiguous or misleading. Examining the genomic
      transmission network in the context of interfacility patient transfers (patient
      sharing networks) supported the role of patient transfers in driving the
      outbreak, with genomic analysis revealing that a small subset of patient-transfer
      events was sufficient to explain regional spread. Further integration of the
      genomic and patient-sharing networks identified one nursing home as an important
      bridge facility early in the outbreak-a role that was not apparent from analysis
      of genomic or patient-transfer data alone. Last, we found that when simulating a
      real-time regional outbreak, our methodology was able to accurately infer the
      facility at which patients acquired their infections. This approach has the
      potential to identify facilities with high rates of intra- or interfacility
      transmission, data that will be useful for triggering targeted interventions to
      prevent further spread of multidrug-resistant organisms.

PMID- 29167392
TI  - TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and
      leukemic clearance.
AB  - Chimeric antigen receptor (CAR)-expressing T cells induce durable remissions in
      patients with relapsed/refractory B cell malignancies. CARs are synthetic
      constructs that, when introduced into mature T cells, confer a second, non-major
      histocompatibility complex-restricted specificity in addition to the endogenous T
      cell receptor (TCR). The implications of TCR activation on CAR T cell efficacy
      has not been well defined. Using an immunocompetent, syngeneic murine model of
      CD19-targeted CAR T cell therapy for pre-B cell acute lymphoblastic leukemia in
      which the CAR is introduced into T cells with known TCR specificity, we
      demonstrate loss of CD8 CAR T cell efficacy associated with T cell exhaustion and
      apoptosis when TCR antigen is present. CD4 CAR T cells demonstrate equivalent
      cytotoxicity to CD8 CAR T cells and, in contrast, retain in vivo efficacy despite
      TCR stimulation. Gene expression profiles confirm increased exhaustion and
      apoptosis of CD8 CAR T cells upon dual receptor stimulation compared to CD4 CAR T
      cells and indicate inherent differences between CD4 and CD8 CAR T cells in the
      use of T cell-associated signaling pathways. These results provide insights into
      important aspects of CAR T cell immune biology and indicate opportunities to
      rationally design CAR constructs to optimize clinical efficacy.

PMID- 29167393
TI  - What evidence do we need for biomarker qualification?
AB  - Biomarkers can facilitate all aspects of the drug development process. However,
      biomarker qualification-the use of a biomarker that is accepted by the U.S. Food
      and Drug Administration-needs a clear, predictable process. We describe a
      multistakeholder effort including government, industry, and academia that
      proposes a framework for defining the amount of evidence needed for biomarker
      qualification. This framework is intended for broad applications across multiple
      biomarker categories and uses.

PMID- 29167394
TI  - Prion seeding activity and infectivity in skin samples from patients with
      sporadic Creutzfeldt-Jakob disease.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease,
      is transmissible through iatrogenic routes due to abundant infectious prions
      [misfolded forms of the prion protein (PrPSc)] in the central nervous system
      (CNS). Some epidemiological studies have associated sCJD risk with non-CNS
      surgeries. We explored the potential prion seeding activity and infectivity of
      skin from sCJD patients. Autopsy or biopsy skin samples from 38 patients [21
      sCJD, 2 variant CJD (vCJD), and 15 non-CJD] were analyzed by Western blotting and
      real-time quaking-induced conversion (RT-QuIC) for PrPSc Skin samples from two
      patients were further examined for prion infectivity by bioassay using two lines
      of humanized transgenic mice. Western blotting revealed dermal PrPSc in one of
      five deceased sCJD patients and one of two vCJD patients. However, the more
      sensitive RT-QuIC assay detected prion seeding activity in skin from all 23 CJD
      decedents but not in skin from any non-CJD control individuals (with other
      neurological conditions or other diseases) during blinded testing. Although sCJD
      patient skin contained ~103- to 105-fold lower prion seeding activity than did
      sCJD patient brain tissue, all 12 mice from two transgenic mouse lines inoculated
      with sCJD skin homogenates from two sCJD patients succumbed to prion disease
      within 564 days after inoculation. Our study demonstrates that the skin of sCJD
      patients contains both prion seeding activity and infectivity, which raises
      concerns about the potential for iatrogenic sCJD transmission via skin.

PMID- 29167395
TI  - Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of
      biliary atresia.
AB  - Biliary atresia is a progressive infantile cholangiopathy of complex
      pathogenesis. Although early diagnosis and surgery are the best predictors of
      treatment response, current diagnostic approaches are imprecise and time
      consuming. We used large-scale, quantitative serum proteomics at the time of
      diagnosis of biliary atresia and other cholestatic syndromes (serving as disease
      controls) to identify biomarkers of disease. In a discovery cohort of 70
      subjects, the lead biomarker was matrix metalloproteinase-7 (MMP-7), which
      retained high distinguishing features for biliary atresia in two validation
      cohorts. Notably, the diagnostic performance reached 95% when MMP-7 was combined
      with gamma-glutamyltranspeptidase (GGT), a marker of cholestasis. Using human
      tissue and an experimental model of biliary atresia, we found that MMP-7 is
      primarily expressed by cholangiocytes, released upon epithelial injury, and
      promotes the experimental disease phenotype. Thus, we propose that serum MMP-7
      (alone or in combination with GGT) is a diagnostic biomarker for biliary atresia
      and may serve as a therapeutic target.

PMID- 29167397
TI  - Rethinking the Role of Thought Suppression in Psychological Models and Treatment.

PMID- 29167398
TI  - Perspectives on Treatment of Alzheimer's Disease: A Closer Look into EphB2
      Depletion.

PMID- 29167396
TI  - Targeting STUB1-tissue factor axis normalizes hyperthrombotic uremic phenotype
      without increasing bleeding risk.
AB  - Chronic kidney disease (CKD/uremia) remains vexing because it increases the risk
      of atherothrombosis and is also associated with bleeding complications on
      standard antithrombotic/antiplatelet therapies. Although the associations of
      indolic uremic solutes and vascular wall proteins [such as tissue factor (TF) and
      aryl hydrocarbon receptor (AHR)] are being defined, the specific mechanisms that
      drive the thrombotic and bleeding risks are not fully understood. We now present
      an indolic solute-specific animal model, which focuses on solute-protein
      interactions and shows that indolic solutes mediate the hyperthrombotic phenotype
      across all CKD stages in an AHR- and TF-dependent manner. We further demonstrate
      that AHR regulates TF through STIP1 homology and U-box-containing protein 1
      (STUB1). As a ubiquitin ligase, STUB1 dynamically interacts with and degrades TF
      through ubiquitination in the uremic milieu. TF regulation by STUB1 is supported
      in humans by an inverse relationship of STUB1 and TF expression and reduced STUB1
      TF interaction in uremic vessels. Genetic or pharmacological manipulation of
      STUB1 in vascular smooth muscle cells inhibited thrombosis in flow loops. STUB1
      perturbations reverted the uremic hyperthrombotic phenotype without prolonging
      the bleeding time, in contrast to heparin, the standard-of-care antithrombotic in
      CKD patients. Our work refines the thrombosis axis (STUB1 is a mediator of
      indolic solute-AHR-TF axis) and expands the understanding of the interconnected
      relationships driving the fragile thrombotic state in CKD. It also establishes a
      means of minimizing the uremic hyperthrombotic phenotype without altering the
      hemostatic balance, a long-sought-after combination in CKD patients.

PMID- 29167400
TI  - Tonotopic Variation of the T-Type Ca2+ Current in Avian Auditory Coincidence
      Detector Neurons.
AB  - Neurons in avian nucleus laminaris (NL) are binaural coincidence detectors for
      sound localization and are characterized by striking structural variations in
      dendrites and axon initial segment (AIS) according to their acoustic tuning
      [characteristic frequency (CF)]. T-type Ca2+ (CaT) channels regulate synaptic
      integration and firing behavior at these neuronal structures. However, whether or
      how CaT channels contribute to the signal processing in NL neurons is not known.
      In this study, we addressed this issue with whole-cell recording and two-photon
      Ca2+ imaging in brain slices of posthatch chicks of both sexes. We found that the
      CaT current was prominent in low-CF neurons, whereas it was almost absent in
      higher-CF neurons. In addition, a large Ca2+ transient occurred at the dendrites
      and the AIS of low-CF neurons, indicating a localization of CaT channels at these
      structures in the neurons. Because low-CF neurons have long dendrites, dendritic
      CaT channels may compensate for the attenuation of EPSPs at dendrites.
      Furthermore, the short distance of AIS from the soma may accelerate activation of
      axonal CaT current in the neurons and help EPSPs reach spike threshold. Indeed,
      the CaT current was activated by EPSPs and augmented the synaptic response and
      spike generation of the neurons. Notably, the CaT current was inactivated during
      repetitive inputs, and these augmenting effects predominated at the initial phase
      of synaptic activity. These results suggested that dendritic and axonal CaT
      channels increase the sensitivity to sound at its onset, which may expand the
      dynamic range for binaural computation in low-CF NL neurons.SIGNIFICANCE
      STATEMENT Neurons in nucleus laminaris are binaural coincidence detectors for
      sound localization. We report that T-type Ca2+ (CaT) current was prominent at
      dendrites and the axonal trigger zone in neurons tuned to low-frequency sound.
      Because these neurons have long dendrites and a closer trigger zone compared with
      those tuned to higher-frequency sound, the CaT current augmented EPSPs at
      dendrites and accelerated spike triggers in the neurons, implying a strategic
      arrangement of the current within the nucleus. This effect was limited to the
      onset of repetitive inputs due to progressive inactivation of CaT current. The
      results suggested that the CaT current increases the sensitivity to sound at its
      onset, which may expand the dynamic range for binaural computation of low
      frequency sound.

PMID- 29167399
TI  - Protein O-Mannosyltransferases Affect Sensory Axon Wiring and Dynamic Chirality
      of Body Posture in the Drosophila Embryo.
AB  - Genetic defects in protein O-mannosyltransferase 1 (POMT1) and POMT2 underlie
      severe muscular dystrophies. POMT genes are evolutionarily conserved in metazoan
      organisms. In Drosophila, both male and female POMT mutants show a clockwise
      rotation of adult abdominal segments, suggesting a chirality of underlying
      pathogenic mechanisms. Here we described and analyzed a similar phenotype in POMT
      mutant embryos that shows left-handed body torsion. Our experiments demonstrated
      that coordinated muscle contraction waves are associated with asymmetric embryo
      rolling, unveiling a new chirality marker in Drosophila development. Using
      genetic and live-imaging approaches, we revealed that the torsion phenotype
      results from differential rolling and aberrant patterning of peristaltic waves of
      muscle contractions. Our results demonstrated that peripheral sensory neurons are
      required for normal contractions that prevent the accumulation of torsion. We
      found that POMT mutants show abnormal axonal connections of sensory neurons. POMT
      transgenic expression limited to sensory neurons significantly rescued the
      torsion phenotype, axonal connectivity defects, and abnormal contractions in POMT
      mutant embryos. Together, our data suggested that protein O-mannosylation is
      required for normal sensory feedback to control coordinated muscle contractions
      and body posture. This mechanism may shed light on analogous functions of POMT
      genes in mammals and help to elucidate the etiology of neurological defects in
      muscular dystrophies.SIGNIFICANCE STATEMENT Protein O-mannosyltransferases
      (POMTs) are evolutionarily conserved in metazoans. Mutations in POMTs cause
      severe muscular dystrophies associated with pronounced neurological defects.
      However, neurological functions of POMTs remain poorly understood. We
      demonstrated that POMT mutations in Drosophila result in abnormal muscle
      contractions and cause embryo torsion. Our experiments uncovered a chirality of
      embryo movements and a unique POMT-dependent mechanism that maintains symmetry of
      a developing system affected by chiral forces. Furthermore, POMTs were found to
      be required for proper axon connectivity of sensory neurons, suggesting that O
      mannosylation regulates the sensory feedback controlling muscle contractions.
      This novel POMT function in the peripheral nervous system may shed light on
      analogous functions in mammals and help to elucidate pathomechanisms of
      neurological abnormalities in muscular dystrophies.

PMID- 29167401
TI  - Acetaminophen Relieves Inflammatory Pain through CB1 Cannabinoid Receptors in the
      Rostral Ventromedial Medulla.
AB  - Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug with
      only incompletely understood mechanisms of action. Previous work, using models of
      acute nociceptive pain, indicated that analgesia by acetaminophen involves an
      indirect activation of CB1 receptors by the acetaminophen metabolite and
      endocannabinoid reuptake inhibitor AM 404. However, the contribution of the
      cannabinoid system to antihyperalgesia against inflammatory pain, the main
      indication of acetaminophen, and the precise site of the relevant CB1 receptors
      have remained elusive. Here, we analyzed acetaminophen analgesia in mice of
      either sex with inflammatory pain and found that acetaminophen exerted a dose
      dependent antihyperalgesic action, which was mimicked by intrathecally injected
      AM 404. Both compounds lost their antihyperalgesic activity in CB1-/- mice,
      confirming the involvement of the cannabinoid system. Consistent with a mechanism
      downstream of proinflammatory prostaglandin formation, acetaminophen also
      reversed hyperalgesia induced by intrathecal prostaglandin E2 To distinguish
      between a peripheral/spinal and a supraspinal action, we administered
      acetaminophen and AM 404 to hoxB8-CB1-/- mice, which lack CB1 receptors from the
      peripheral nervous system and the spinal cord. These mice exhibited unchanged
      antihyperalgesia indicating a supraspinal site of action. Accordingly, local
      injection of the CB1 receptor antagonist rimonabant into the rostral ventromedial
      medulla blocked acetaminophen-induced antihyperalgesia, while local rostral
      ventromedial medulla injection of AM 404 reduced hyperalgesia in wild-type mice
      but not in CB1-/- mice. Our results indicate that the cannabinoid system
      contributes not only to acetaminophen analgesia against acute pain but also
      against inflammatory pain, and suggest that the relevant CB1 receptors reside in
      the rostral ventromedial medulla.SIGNIFICANCE STATEMENT Acetaminophen is a widely
      used analgesic drug with multiple but only incompletely understood mechanisms of
      action, including a facilitation of endogenous cannabinoid signaling via one of
      its metabolites. Our present data indicate that enhanced cannabinoid signaling is
      also responsible for the analgesic effects of acetaminophen against inflammatory
      pain. Local injections of the acetaminophen metabolite AM 404 and of cannabinoid
      receptor antagonists as well as data from tissue-specific CB1 receptor-deficient
      mice suggest the rostral ventromedial medulla as an important site of the
      cannabinoid-mediated analgesia by acetaminophen.

PMID- 29167402
TI  - The Role of Cysteine String Protein alpha Phosphorylation at Serine 10 and 34 by
      Protein Kinase Cgamma for Presynaptic Maintenance.
AB  - Protein kinase Cgamma (PKCgamma) knock-out (KO) animals exhibit symptoms of
      Parkinson's disease (PD), including dopaminergic neuronal loss in the substantia
      nigra. However, the PKCgamma substrates responsible for the survival of
      dopaminergic neurons in vivo have not yet been elucidated. Previously, we found
      10 potent substrates in the striatum of PKCgamma-KO mice. Here, we focused on
      cysteine string protein alpha (CSPalpha), a protein from the heat shock protein
      (HSP) 40 cochaperone families localized on synaptic vesicles. We found that in
      cultured cells, PKCgamma phosphorylates CSPalpha at serine (Ser) 10 and Ser34.
      Additionally, apoptosis was found to have been enhanced by the overexpression of
      a phosphorylation-null mutant of CSPalpha, CSPalpha(S10A/S34A). Compared with
      wild-type (WT) CSPalpha, the CSPalpha(S10A/S34A) mutant had a weaker interaction
      with HSP70. However, in sharp contrast, a phosphomimetic CSPalpha(S10D/S34D)
      mutant, compared with WT CSPalpha, had a stronger interaction with HSP70. In
      addition, total levels of synaptosomal-associated protein (SNAP) 25, a main
      downstream target of the HSC70/HSP70 chaperone complex, were found to have
      decreased by the CSPalpha(S10A/S34A) mutant through increased ubiquitination of
      SNAP25 in PC12 cells. In the striatum of 2-year-old male PKCgamma-KO mice,
      decreased phosphorylation levels of CSPalpha and decreased SNAP25 protein levels
      were observed. These findings indicate the phosphorylation of CSPalpha by
      PKCgamma may protect the presynaptic terminal from neurodegeneration. The
      PKCgamma-CSPalpha-HSC70/HSP70-SNAP25 axis, because of its role in protecting the
      presynaptic terminal, may provide a new therapeutic target for the treatment of
      PD.SIGNIFICANCE STATEMENT Cysteine string protein alpha (CSPalpha) is a protein
      belonging to the heat shock protein (HSP) 40 cochaperone families localized on
      synaptic vesicles, which maintain the presynaptic terminal. However, the function
      of CSPalpha phosphorylation by protein kinase C (PKC) for neuronal cell survival
      remains unclear. The experiments presented here demonstrate that PKCgamma
      phosphorylates CSPalpha at serine (Ser) 10 and Ser34. CSPalpha phosphorylation at
      Ser10 and Ser34 by PKCgamma protects the presynaptic terminal by promoting HSP70
      chaperone activity. This report suggests that CSPalpha phosphorylation, because
      of its role in modulating HSP70 chaperone activity, may be a target for the
      treatment of neurodegeneration.

PMID- 29167403
TI  - Alpha Oscillations Reduce Temporal Long-Range Dependence in Spontaneous Human
      Brain Activity.
AB  - Ongoing neural dynamics comprise both frequency-specific oscillations and
      broadband-features, such as long-range dependence (LRD). Despite both being
      behaviorally relevant, little is known about their potential interactions. In
      humans, 8-12 Hz alpha oscillations constitute the strongest deviation from 1/f
      power-law scaling, the signature of LRD. We postulated that alpha oscillations,
      believed to exert active inhibitory gating, downmodulate the temporal width of
      LRD in slower ongoing brain activity. In two independent "resting-state" datasets
      (electroencephalography surface recordings and magnetoencephalography source
      reconstructions), both across space and dynamically over time, power of alpha
      activity covaried with the power slope <5 Hz (i.e., greater alpha activity
      shortened LRD). Causality of alpha activity dynamics was implied by its temporal
      precedence over changes of slope. A model where power-law fluctuations of the
      alpha envelope inhibit baseline activity closely replicated our results. Thus,
      alpha oscillations may provide an active control mechanism to adaptively regulate
      LRD of brain activity at slow temporal scales, thereby shaping internal states
      and cognitive processes.SIGNIFICANCE STATEMENT The two prominent features of
      ongoing brain activity are oscillations and temporal long-range dependence. Both
      shape behavioral performance, but little is known about their interaction. Here,
      we demonstrate such an interaction in EEG and MEG recordings of task-free human
      brain activity. Specifically, we show that spontaneous dynamics in alpha activity
      explain ensuing variations of dependence in the low and ultra-low-frequency
      range. In modeling, two features of alpha oscillations are critical to account
      for the observed effects on long-range dependence, scale-free properties of alpha
      oscillations themselves, and a modulation of baseline levels, presumably
      inhibitory. Both these properties have been observed empirically, and our study
      hence establishes alpha oscillations as a regulatory mechanism governing long
      range dependence or "memory" in slow ongoing brain activity.

PMID- 29167404
TI  - A Critical Role for Dopamine D5 Receptors in Pain Chronicity in Male Mice.
AB  - Dopaminergic modulation of spinal cord plasticity has long been recognized, but
      circuits affected by this system and the precise receptor subtypes involved in
      this modulation have not been defined. Dopaminergic modulation from the A11
      nucleus of the hypothalamus contributes to plasticity in a model of chronic pain
      called hyperalgesic priming. Here we tested the hypothesis that the key receptor
      subtype mediating this effect is the D5 receptor (D5R). We find that a spinally
      directed lesion of dopaminergic neurons reverses hyperalgesic priming in both
      sexes and that a D1/D5 antagonist transiently inhibits neuropathic pain. We used
      mice lacking D5Rs (DRD5KO mice) to show that carrageenan, interleukin 6, as well
      as BDNF-induced hyperalgesia and priming are reduced specifically in male mice.
      These male DRD5KO mice also show reduced formalin pain responses and decreased
      heat pain. To characterize the subtypes of dorsal horn neurons engaged by
      dopamine signaling in the hyperalgesic priming model, we used c-fos labeling. We
      find that a mixed D1/D5 agonist given spinally to primed mice activates a subset
      of neurons in lamina III and IV of the dorsal horn that coexpress PAX2, a
      transcription factor for GABAergic interneurons. In line with this, we show that
      gabazine, a GABA-A receptor antagonist, is antihyperalgesic in primed mice
      exposed to spinal administration of a D1/D5 agonist. Therefore, the D5R, in
      males, and the D1R, in females, exert a powerful influence over spinal cord
      circuitry in pathological pain likely via modulation of deep dorsal horn
      GABAergic neurons.SIGNIFICANCE STATEMENT Pain is the most prominent reason why
      people seek medical attention, and chronic pain incidence worldwide has been
      estimated to be as high as 33%. This study provides new insight into how
      descending dopamine controls pathological pain states. Our work demonstrates that
      dopaminergic spinal projections are necessary for the maintenance of a chronic
      pain state in both sexes; however, D5 receptors seem to play a critical role in
      males whereas females rely more heavily on D1 receptors, an effect that could be
      explained by sexual dimorphisms in receptor expression levels. Collectively, our
      work provides new insights into how the dopaminergic system interacts with spinal
      circuits to promote pain plasticity.

PMID- 29167405
TI  - The Microtubule-Associated Protein Tau Mediates the Organization of Microtubules
      and Their Dynamic Exploration of Actin-Rich Lamellipodia and Filopodia of
      Cortical Growth Cones.
AB  - Proper organization and dynamics of the actin and microtubule (MT) cytoskeleton
      are essential for growth cone behaviors during axon growth and guidance. The MT
      associated protein tau is known to mediate actin/MT interactions in cell-free
      systems but the role of tau in regulating cytoskeletal dynamics in living neurons
      is unknown. We used cultures of cortical neurons from postnatal day (P)0-P2
      golden Syrian hamsters (Mesocricetus auratus) of either sex to study the role of
      tau in the organization and dynamics of the axonal growth cone cytoskeleton.
      Here, using super resolution microscopy of fixed growth cones, we found that tau
      colocalizes with MTs and actin filaments and is also located at the interface
      between actin filament bundles and dynamic MTs in filopodia, suggesting that tau
      links these two cytoskeletons. Live cell imaging in concert with shRNA tau
      knockdown revealed that reducing tau expression disrupts MT bundling in the
      growth cone central domain, misdirects trajectories of MTs in the transition
      region and prevents single dynamic MTs from extending into growth cone filopodia
      along actin filament bundles. Rescue experiments with human tau expression
      restored MT bundling, MT penetration into the growth cone periphery and close MT
      apposition to actin filaments in filopodia. Importantly, we found that tau
      knockdown reduced axon outgrowth and growth cone turning in Wnt5a gradients,
      likely due to disorganized MTs that failed to extend into the peripheral domain
      and enter filopodia. These results suggest an important role for tau in
      regulating cytoskeletal organization and dynamics during growth cone
      behaviors.SIGNIFICANCE STATEMENT Growth cones are the motile tips of growing
      axons whose guidance behaviors require interaction of the dynamic actin and
      microtubule cytoskeleton. Tau is a microtubule-associated protein that stabilizes
      microtubules in neurons and in cell-free systems regulates actin-microtubule
      interaction. Here, using super resolution microscopy, live-cell imaging, and tau
      knockdown, we show for the first time in living axonal growth cones that tau is
      important for microtubule bundling and microtubule exploration of the actin-rich
      growth cone periphery. Importantly tau knockdown reduced axon outgrowth and
      growth cone turning, due to disorganized microtubules that fail to enter
      filopodia and co-align with actin filaments. Understanding normal tau functions
      will be important for identifying mechanisms of tau in neurodegenerative diseases
      such as Alzheimer's.

PMID- 29167406
TI  - Inverted Encoding Models of Human Population Response Conflate Noise and Neural
      Tuning Width.
AB  - Channel-encoding models offer the ability to bridge different scales of neuronal
      measurement by interpreting population responses, typically measured with BOLD
      imaging in humans, as linear sums of groups of neurons (channels) tuned for
      visual stimulus properties. Inverting these models to form predicted channel
      responses from population measurements in humans seemingly offers the potential
      to infer neuronal tuning properties. Here, we test the ability to make inferences
      about neural tuning width from inverted encoding models. We examined contrast
      invariance of orientation selectivity in human V1 (both sexes) and found that
      inverting the encoding model resulted in channel response functions that became
      broader with lower contrast, thus apparently violating contrast invariance.
      Simulations showed that this broadening could be explained by contrast-invariant
      single-unit tuning with the measured decrease in response amplitude at lower
      contrast. The decrease in response lowers the signal-to-noise ratio of population
      responses that results in poorer population representation of orientation.
      Simulations further showed that increasing signal to noise makes channel response
      functions less sensitive to underlying neural tuning width, and in the limit of
      zero noise will reconstruct the channel function assumed by the model regardless
      of the bandwidth of single units. We conclude that our data are consistent with
      contrast-invariant orientation tuning in human V1. More generally, our results
      demonstrate that population selectivity measures obtained by encoding models can
      deviate substantially from the behavior of single units because they conflate
      neural tuning width and noise and are therefore better used to estimate the
      uncertainty of decoded stimulus properties.SIGNIFICANCE STATEMENT It is widely
      recognized that perceptual experience arises from large populations of neurons,
      rather than a few single units. Yet, much theory and experiment have examined
      links between single units and perception. Encoding models offer a way to bridge
      this gap by explicitly interpreting population activity as the aggregate response
      of many single neurons with known tuning properties. Here we use this approach to
      examine contrast-invariant orientation tuning of human V1. We show with
      experiment and modeling that due to lower signal to noise, contrast-invariant
      orientation tuning of single units manifests in population response functions
      that broaden at lower contrast, rather than remain contrast-invariant. These
      results highlight the need for explicit quantitative modeling when making a
      reverse inference from population response profiles to single-unit responses.

PMID- 29167407
TI  - Dissociable Decoding of Spatial Attention and Working Memory from EEG
      Oscillations and Sustained Potentials.
AB  - In human scalp EEG recordings, both sustained potentials and alpha-band
      oscillations are present during the delay period of working memory tasks and may
      therefore reflect the representation of information in working memory. However,
      these signals may instead reflect support mechanisms rather than the actual
      contents of memory. In particular, alpha-band oscillations have been tightly tied
      to spatial attention and may not reflect location-independent memory
      representations per se. To determine how sustained and oscillating EEG signals
      are related to attention and working memory, we attempted to decode which of 16
      orientations was being held in working memory by human observers (both women and
      men). We found that sustained EEG activity could be used to decode the remembered
      orientation of a stimulus, even when the orientation of the stimulus varied
      independently of its location. Alpha-band oscillations also carried clear
      information about the location of the stimulus, but they provided little or no
      information about orientation independently of location. Thus, sustained
      potentials contain information about the object properties being maintained in
      working memory, consistent with previous evidence of a tight link between these
      potentials and working memory capacity. In contrast, alpha-band oscillations
      primarily carry location information, consistent with their link to spatial
      attention.SIGNIFICANCE STATEMENT Working memory plays a key role in cognition,
      and working memory is impaired in several neurological and psychiatric disorders.
      Previous research has suggested that human scalp EEG recordings contain signals
      that reflect the neural representation of information in working memory. However,
      to conclude that a neural signal actually represents the object being remembered,
      it is necessary to show that the signal contains fine-grained information about
      that object. Here, we show that sustained voltages in human EEG recordings
      contain fine-grained information about the orientation of an object being held in
      memory, consistent with a memory storage signal.

PMID- 29167408
TI  - Conjugated linoleic acid prevents age-dependent neurodegeneration in a mouse
      model of neuropsychiatric lupus via the activation of an adaptive response.
AB  - Oxidative stress is a key mediator of autoimmune/neurodegenerative disorders. The
      antioxidant/anti-inflammatory effect of a synthetic conjugated linoleic acid
      (CLA) mixture in MRL/MpJ-Fas lpr mice (MRL/lpr), an animal model of
      neuropsychiatric lupus, was previously associated with the improvement of nuclear
      factor-E2-related factor 2 (Nrf2) defenses in the spleen and liver. However,
      little is known about the neuroprotective ability of a CLA mixture. This study
      investigated the age-dependent progression of oxidative stress and the
      hyperactivation of redox-sensitive compensatory pathways (macroautophagy, Nrf2)
      in old/diseased MRL/lpr mice brains and examines the effect produced by dietary
      CLA supplementation. Disrupted redox homeostasis was evidenced in the blood,
      liver, and brain of 21- to 22-week-old MRL/lpr (Old) mice compared with 8- to 10
      week-old MRL/lpr (Young) animals. This alteration was associated with significant
      hyperactivation of compensatory mechanisms (macroautophagy, Nrf2, and astrocyte
      activation) in the brains of Old mice. Five-week daily supplementation with CLA
      (650 mg/kg-1 body weight) of 16-week-old (CLA+Old) mice diminished all the
      pathological hallmarks at a level comparable to Young mice or healthy controls
      (BALB/c). Such data demonstrated that MRL/lpr mice can serve as a valuable model
      for the evaluation of the effectiveness of neuroprotective drugs. Notably, the
      preventive effect provided by CLA supplementation against age-associated neuronal
      damage and hyperactivation of compensatory mechanisms suggests that the
      activation of an adaptive response is at least in part accountable for its
      neuroprotective ability.

PMID- 29167410
TI  - Molecular mechanisms underlying catalytic activity of delta 6 desaturase from
      Glossomastix chrysoplasta and Thalassiosira pseudonana.
AB  - Delta 6 desaturase (FADS2) is a critical bifunctional enzyme required for PUFA
      biosynthesis. In some organisms, FADS2s have high substrate specificity, whereas
      in others, they have high catalytic activity. Previously, we analyzed the
      molecular mechanisms underlying high FADS2 substrate specificity; in this study,
      we assessed those underlying the high catalytic activity of FADS2s from
      Glossomastix chrysoplasta and Thalassiosira pseudonana To understand the
      structural basis of this catalytic activity, GcFADS2 and TpFADS2 sequences were
      divided into nine sections, and a domain-swapping approach was applied to examine
      the role of each section in facilitating the catalytic activity of the overall
      protein. The results revealed two regions essential to this process: one that
      extends from the end of the fourth to the beginning of the fifth cytoplasmic
      transmembrane domain, and another that includes the C-terminal region that occurs
      after the sixth cytoplasmic transmembrane domain. Based on the domain-swapping
      analyses, the amino acid residues at ten sites were identified to differ between
      the GcFADS2 and TpFADS2 sequences, and therefore further analyzed by site
      directed mutagenesis. T302V, S322A, Y375F, and M384S/M385 substitutions in
      TpFADS2 significantly affected FADS2 catalytic efficiency. This study offers a
      solid basis for in-depth understanding of catalytic efficiency of FADS2.

PMID- 29167409
TI  - Sphingosine 1-phosphate activation of ERM contributes to vascular calcification.
AB  - Vascular calcification is the deposition of mineral in the artery wall by
      vascular smooth muscle cells (VSMCs) in response to pathological stimuli. The
      process is similar to bone formation and is an independent risk factor for
      cardiovascular disease. Given that ceramide and sphingosine 1-phosphate (S1P) are
      involved in cardiovascular pathophysiology and biomineralization, their role in
      VSMC matrix mineralization was investigated. During phosphate-induced VSMC
      mineralization, endogenous S1P levels increased accompanied by increased
      sphingosine kinase (SK) activity and increased mRNA expression of SK1 and SK2.
      Consistent with this, mineralization was increased by exogenous S1P, but
      decreased by C2-ceramide. Mechanistically, exogenous S1P stimulated ezrin-radixin
      moesin (ERM) phosphorylation in VSMCs and ERM phosphorylation was increased
      concomitantly with endogenous S1P during mineralization. Moreover, inhibition of
      acid sphingomyelinase and ceramidase with desipramine prevented increased S1P
      levels, ERM activation, and mineralization. Finally, pharmacological inhibition
      of ERM phosphorylation with NSC663894 decreased mineralization induced by
      phosphate and exogenous S1P. Although further studies will be needed to verify
      these findings in vivo, this study defines a novel role for the SK-S1P-ERM
      pathways in phosphate-induced VSMC matrix mineralization and shows that blocking
      these pathways with pharmacological inhibitors reduces mineralization. These
      results may inform new therapeutic approaches to inhibit or delay vascular
      calcification.

PMID- 29167411
TI  - 2-Chlorofatty acids induce Weibel-Palade body mobilization.
AB  - Endothelial dysfunction is a hallmark of multiple inflammatory diseases.
      Leukocyte interactions with the endothelium have significant effects on vascular
      wall biology and pathophysiology. Myeloperoxidase (MPO)-derived oxidant products
      released from leukocytes are potential mediators of inflammation and endothelial
      dysfunction. 2-Chlorofatty acids (2-ClFAs) are produced as a result of MPO
      derived HOCl targeting plasmalogen phospholipids. Chlorinated lipids have been
      shown to be associated with multiple inflammatory diseases, but their impact on
      surrounding endothelial cells has not been examined. This study tested the
      biological properties of the 2-ClFA molecular species 2-chlorohexadecanoic acid
      (2-ClHA) on endothelial cells. A synthetic alkyne analog of 2-ClHA, 2
      chlorohexadec-15-ynoic acid (2-ClHyA), was used to examine the subcellular
      localization of 2-ClFA in human coronary artery endothelial cells. Click
      chemistry experiments revealed that 2-ClHyA localizes to Weibel-Palade bodies. 2
      ClHA and 2-ClHyA promote the release of P-selectin, von Willebrand factor, and
      angiopoietin-2 from endothelial cells. Functionally, 2-ClHA and 2-ClHyA cause
      neutrophils to adhere to and platelets to aggregate on the endothelium, as well
      as increase permeability of the endothelial barrier which has been tied to the
      release of angiopoietin-2. These findings suggest that 2-ClFAs promote
      endothelial cell dysfunction, which may lead to broad implications in
      inflammation, thrombosis, and blood vessel stability.

PMID- 29167412
TI  - PEMT, Delta6 desaturase, and palmitoyldocosahexaenoyl phosphatidylcholine are
      increased in rats during pregnancy.
AB  - DHA is important for fetal neurodevelopment. During pregnancy, maternal plasma
      DHA increases, but the mechanism is not fully understood. Using rats fed a fixed
      formula diet (DHA as 0.07% total energy), plasma and liver were collected for
      fatty acid profiling before pregnancy, at 15 and 20 days of pregnancy, and 7 days
      postpartum. Phosphatidylethanolamine methyltransferase (PEMT) and enzymes
      involved in PUFA synthesis were examined in liver. Ad hoc transcriptomic and
      lipidomic analyses were also performed. With pregnancy, DHA increased in liver
      and plasma lipids, with a large increase in plasma DHA between day 15 and day 20
      that was mainly attributed to an increase in 16:0/DHA phosphatidylcholine (PC) in
      liver (2.6-fold) and plasma (3.9-fold). Increased protein levels of Delta6
      desaturase (FADS2) and PEMT at day 20 and increased Pemt expression and PEMT
      activity at day 15 suggest that during pregnancy, both DHA synthesis and 16:0/DHA
      PC synthesis are upregulated. Transcriptomic analysis revealed minor changes in
      the expression of genes related to phospholipid synthesis, but little insight on
      DHA metabolism. Hepatic PEMT appears to be the mechanism for increased plasma
      16:0/DHA PC, which is supported by increased DHA biosynthesis based on increased
      FADS2 protein levels.

PMID- 29167414
TI  - Biomarkers related to respiratory symptoms and lung function in adults with
      asthma.
AB  - BACKGROUND: There is a need for easily measurable biomarkers that are able to
      identify different levels of asthma severity. AIM: To assess the association
      between peripheral blood cell counts, fractional nitric oxide in exhaled air
      (FeNO), urinary biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and 8
      isoprostane), and asthma severity in adult patients from the general population.
      METHODS: In the Gene Environment Interactions in Respiratory Diseases study, 287
      subjects with asthma (aged 20-64) were identified from the general population in
      Verona (Italy) (2008-2010). Self-reported asthma attacks, asthma-like symptoms
      and the use of hospital services in the past year were synthesized in a score of
      respiratory symptoms (SRS). The association of biomarkers with SRS and lung
      function measures (pre-bronchodilator FEV1% predicted and FEV1/FVC) was assessed
      using quasi-Poisson and Gaussian regression models, respectively. RESULTS:
      Eosinophils (ratio of expected scores: RES[95%CI] = 1.19[1.09,1.30]), basophils
      (RES[95%CI] = 1.24[1.10,1.40]), lymphocytes (RES[95%CI] = 1.27[1.12,1.45]) and
      FeNO (RES[95%CI] = 1.18[1.02,1.37]) were positively associated with SRS. However,
      only eosinophils (RES[95%CI] = 1.15[1.02,1.30]) and lymphocytes (RES[95%CI] =
      1.25[1.06,1.47]) showed an independent association. Furthermore, eosinophils
      (change in the expected outcome for 1-SD increase: CEO[95%CI] = -1.18[-2.09, 
      0.27]%), basophils (CEO[95%CI] = -1.24[-2.16, -0.33]%) and lymphocytes
      (CEO[95%CI] = -1.07[-1.99, -0.14]%) were individually, but not independently,
      associated with FEV1/FVC. Finally, neutrophils were negatively associated with
      FEV1% predicted (CEO[95%CI] = -2.22[-4.00, -0.44]%). CONCLUSIONS: We identified a
      pattern of association between a set of biomarkers and asthma endotypes in adult
      patients from the general population, which could improve understanding of the
      heterogeneity and severity of the disease and could be useful in defining
      targeted therapeutic approaches.

PMID- 29167413
TI  - Occurrence and biological activity of palmitoleic acid isomers in phagocytic
      cells.
AB  - Recent studies have highlighted the role of palmitoleic acid [16:1n-7 (cis-9
      hexadecenoic acid)] as a lipid hormone that coordinates cross-talk between liver
      and adipose tissue and exerts anti-inflammatory protective effects on hepatic
      steatosis and insulin signaling in murine models of metabolic disease. More
      recently, a 16:1n-7 isomer, cis-7-hexadecenoic acid (16:1n-9), that also
      possesses marked anti-inflammatory effects, has been described in human
      circulating monocytes and monocyte-derived macrophages. By using gas
      chromatographic/mass spectrometric analyses of dimethyl disulfide derivatives of
      fatty acyl methyl esters, we describe in this study the presence of a third 16:1
      isomer, sapienic acid [16:1n-10 (6-cis-hexadecenoic acid)], in phagocytic cells.
      Cellular levels of 16:1n-10 appear to depend not only on the cellular content of
      linoleic acid, but also on the expression level of fatty acid desaturase 2, thus
      revealing a complex regulation both at the enzyme level, via fatty acid substrate
      competition, and directly at the gene level. However, unlike 16:1n-7 and 16:1n-9,
      16:1n-10 levels are not regulated by the activation state of the cell. Moreover,
      while 16:1n-7 and 16:1n-9 manifest strong anti-inflammatory activity when added
      to the cells at low concentrations (10 MUM), notably higher concentrations of
      16:1n-10 are required to observe a comparable effect. Collectively, these results
      suggest the presence in phagocytic cells of an unexpected variety of 16:1
      isomers, which can be distinguished on the basis of their biological activity and
      cellular regulation.

PMID- 29167415
TI  - Ticagrelor Leads to Statin-Induced Rhabdomyolysis: A Case Report.
AB  - BACKGROUND Following acute coronary intervention in cardiology patients, the
      combined medical therapy with the platelet inhibitory drug ticagrelor and a
      statin medication (e.g., simvastatin) is recommended according to international
      guidelines. Yet combined therapeutic regimens have the potential of
      pharmacological interaction with both ticagrelor and simvastatin being
      metabolized by CYP3A4. Rhabdomyolysis is a known side-effect of statin therapy
      and combined therapy increases the susceptibility to this complication. CASE
      REPORT A 72-year-old patient presented to our Emergency Department with typical
      signs of rhabdomyolysis consisting of muscular cramps and pain in both legs and a
      significant elevation of creatinine kinase (CK). Five months prior to this
      presentation, he had been hospitalized due to acute coronary syndrome followed by
      a coronary intervention of a high-grade left anterior descending artery stenosis.
      His long-term medication included simvastatin 20 mg daily, which he had taken for
      several years, and ticagrelor, which had been added to his medication following
      coronary intervention. The patient showed fast recovery of symptoms and rapid
      normalization of CK levels upon treatment change from ticagrelor to clopidogrel
      with a paused statin administration. CONCLUSIONS The combined use of ticagrelor
      with low dose simvastatin poses a risk for rhabdomyolysis even in patients with
      normal kidney function. Patients treated with ticagrelor might require changes in
      statin therapy and dose adjustments in order to avoid pharmacological
      interactions and higher risk for adverse effects.

PMID- 29167416
TI  - Second-Look Arthroscopic Evaluation and Clinical Outcomes of Anatomic Anterior
      Cruciate Ligament Reconstruction with Autograft and Hybrid Graft: A Retrospective
      Study.
AB  - BACKGROUND Graft choice is very controversial. This study compared the second
      look evaluation and clinical outcomes of anatomic ACL-R using a thin autograft
      versus a thick hybrid graft. MATERIAL AND METHODS Sixty-eight patients who had
      received ACL-R with hamstring autograft or autograft-allograft hybrid graft
      accepted second-look arthroscopy were grouped (autograft: n=31, age: 32.8+/-8.9,
      Male/Female: 16/15, and hybrid graft: n=37, age: 33.9+/-8.4, Male/Female: 27/10).
      Patients were evaluated with the functional score and KT-1000 test before
      reconstruction. The re-examination and second-look evaluation were performed at 2
      year follow-up. Results were compared and further comparisons were made for
      grafts size >8.5 mm. RESULTS The hybrid group showed thicker graft size and
      bigger graft occupancy (9.0+/-0.5 mm vs. 8.5+/-0.7 mm, P=.003; 80.1+/-7.0% vs.
      69.9+/-6.9%, P8.5 mm were selected and compared (autograft, n=16; hybrid, n=29).
      Graft tension and Synovial coverage showed a significant difference (P=.036 and
      P=.029). The Lysholm, IKDC, and KT-1000 test were significantly superior for the
      autograft than the hybrid graft (P=.036, P=.004, and P=.003, respectively).
      CONCLUSIONS A pure autograft is superior to a hybrid graft with same diameter in
      ACL-R because the augmenting allografts may be null and void. Therefore, a
      homogenous graft is recommended.

PMID- 29167417
TI  - Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3
      causes short QT syndrome.
AB  - Patients with short QT syndrome (SQTS) may present with syncope, ventricular
      fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding
      cation channels, explain <25% of SQTS cases. Here we identify a missense mutation
      in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with
      SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane
      bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac
      pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but
      not mutated SLC4A3. Mechanistic analyses suggest that an increase in pHi and
      decrease in [Cl-]i shortened the action potential duration. However, other
      mechanisms may also play a role. Altered anion transport represents a mechanism
      for development of arrhythmia and may provide new therapeutic possibilities.

PMID- 29167418
TI  - Skyrmion dynamics in a frustrated ferromagnetic film and current-induced helicity
      locking-unlocking transition.
AB  - The helicity-orbital coupling is an intriguing feature of magnetic skyrmions in
      frustrated magnets. Here we explore the skyrmion dynamics in a frustrated magnet
      based on the J 1-J 2-J 3 classical Heisenberg model explicitly by including the
      dipole-dipole interaction. The skyrmion energy acquires a helicity dependence due
      to the dipole-dipole interaction, resulting in the current-induced translational
      motion with a fixed helicity. The lowest-energy states are the degenerate Bloch
      type states, which can be used for building the binary memory. By increasing the
      driving current, the helicity locking-unlocking transition occurs, where the
      translational motion changes to the rotational motion. Furthermore, we
      demonstrate that two skyrmions can spontaneously form a bound state. The
      separation of the bound state forced by a driving current is also studied. In
      addition, we show the annihilation of a pair of skyrmion and antiskyrmion. Our
      results reveal the distinctive frustrated skyrmions may enable viable
      applications in topological magnetism.

PMID- 29167419
TI  - Widespread theta synchrony and high-frequency desynchronization underlies
      enhanced cognition.
AB  - The idea that synchronous neural activity underlies cognition has driven an
      extensive body of research in human and animal neuroscience. Yet, insufficient
      data on intracranial electrical connectivity has precluded a direct test of this
      hypothesis in a whole-brain setting. Through the lens of memory encoding and
      retrieval processes, we construct whole-brain connectivity maps of fast gamma (30
      100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294
      neurosurgical patients fitted with indwelling electrodes. Here we report that
      gamma networks desynchronize and theta networks synchronize during encoding and
      retrieval. Furthermore, for nearly all brain regions we studied, gamma power
      rises as that region desynchronizes with gamma activity elsewhere in the brain,
      establishing gamma as a largely asynchronous phenomenon. The abundant phenomenon
      of theta synchrony is positively correlated with a brain region's gamma power,
      suggesting a predominant low-frequency mechanism for inter-regional
      communication.

PMID- 29167420
TI  - Incidence and risk factors of hepatitis B virus reactivation in patients with
      multiple myeloma in an era with novel agents: a nationwide retrospective study in
      Japan.

PMID- 29167422
TI  - Full-wave modeling of broadband near field scanning microwave microscopy.
AB  - A three-dimensional finite element numerical modeling for the scanning microwave
      microscopy (SMM) setup is applied to study the full-wave quantification of the
      local material properties of samples. The modeling takes into account the
      radiation and scattering losses of the nano-sized probe neglected in previous
      models based on low-frequency assumptions. The scanning techniques of approach
      curves and constant height are implemented. In addition, we conclude that the SMM
      has the potential for use as a broadband dielectric spectroscopy operating at
      higher frequencies up to THz. The results demonstrate the accuracy of previous
      models. We draw conclusions in light of the experimental results.

PMID- 29167421
TI  - Structural insights into substrate and inhibitor binding sites in human
      indoleamine 2,3-dioxygenase 1.
AB  - Human indoleamine 2,3-dioxygenase 1 (hIDO1) is an attractive cancer
      immunotherapeutic target owing to its role in promoting tumoral immune escape.
      However, drug development has been hindered by limited structural information.
      Here, we report the crystal structures of hIDO1 in complex with its substrate,
      Trp, an inhibitor, epacadostat, and/or an effector, indole ethanol (IDE). The
      data reveal structural features of the active site (Sa) critical for substrate
      activation; in addition, they disclose a new inhibitor-binding mode and a
      distinct small molecule binding site (Si). Structure-guided mutation of a
      critical residue, F270, to glycine perturbs the Si site, allowing structural
      determination of an inhibitory complex, where both the Sa and Si sites are
      occupied by Trp. The Si site offers a novel target site for allosteric inhibitors
      and a molecular explanation for the previously baffling substrate-inhibition
      behavior of the enzyme. Taken together, the data open exciting new avenues for
      structure-based drug design.

PMID- 29167423
TI  - Reassessment of chitosanase substrate specificities and classification.
AB  - Chitosanases can be used to produce partially acetylated chitosan
      oligosaccharides (paCOS) for different applications, provided they are thoroughly
      characterized. However, recent studies indicate that the established
      classification system for chitosanases is too simplistic. Here, we apply a highly
      sensitive method for quantitatively sequencing paCOS to reassess the substrate
      specificities of the best-characterized class I-III chitosanases. The enzymes'
      abilities to cleave bonds at GlcNAc residues positioned at subsite (-1) or (+1),
      on which the classification system is based, vary especially when the substrates
      have different fractions of acetylation (F A ). Conflicts with the recent
      classification are observed at higher F A , which were not investigated in prior
      specificity determinations. Initial analyses of pectin-degrading enzymes reveal
      that classifications of other polysaccharide-degrading enzymes should also be
      critically reassessed. Based on our results, we tentatively suggest a chitosanase
      classification system which is based on specificities and preferences of subsites
      (-2) to (+2).

PMID- 29167424
TI  - MiR-92a and miR-486 are potential diagnostic biomarkers for mercury poisoning and
      jointly sustain NF-kappaB activity in mercury toxicity.
AB  - Occupational and environmental exposure to mercury is a public health concern
      worldwide. Although the altered epigenetic regulatory features, such as microRNA,
      have been associated with mercury exposure, the underlying molecular mechanism is
      not well illuminated. This study aimed to confirm that hsa-miR-92a and hsa-miR
      486 are novel diagnostic biomarkers of occupational mercury poisoning, and to
      explore the underlying mechanism of miR-92a and miR-486 in mercury toxicity. RT
      qPCR assays and receiver operating characteristics curve analyses were conducted
      to confirm the diagnostic value of miR-92a and miR-486 as biomarkers of
      occupational mercury poisoning. Dual-luciferase assay was applied to confirm the
      target gene of miR-92a and miR-486 in vitro. Then, we established an in-vitro
      model where miR-92a and miR-486 were overexpressed or knocked down in HEK-293 and
      HUVEC cells. RT-qPCR and western blotting were used to analyze gene and protein
      expression levels. Cell apoptosis was determined by flow cytometry. Results show
      that miR-92a and miR-486 expression levels were up-regulated in workers exposed
      to occupational mercury. Upregulation of miR-92a and miR-486 may play a crucial
      role in mercury toxicity by jointly activating the NF-kappaB signaling pathway
      via targeting KLF4 and Cezanne, respectively.

PMID- 29167425
TI  - Experimentally simulating the dynamics of quantum light and matter at deep-strong
      coupling.
AB  - The quantum Rabi model describing the fundamental interaction between light and
      matter is a cornerstone of quantum physics. It predicts exotic phenomena like
      quantum phase transitions and ground-state entanglement in ultrastrong and deep
      strong coupling regimes, where coupling strengths are comparable to or larger
      than subsystem energies. Demonstrating dynamics remains an outstanding challenge,
      the few experiments reaching these regimes being limited to spectroscopy. Here,
      we employ a circuit quantum electrodynamics chip with moderate coupling between a
      resonator and transmon qubit to realise accurate digital quantum simulation of
      deep-strong coupling dynamics. We advance the state of the art in solid-state
      digital quantum simulation by using up to 90 second-order Trotter steps and
      probing both subsystems in a combined Hilbert space dimension of ~80,
      demonstrating characteristic Schrodinger-cat-like entanglement and large photon
      build-up. Our approach will enable exploration of extreme coupling regimes and
      quantum phase transitions, and demonstrates a clear first step towards larger
      complexities such as in the Dicke model.

PMID- 29167426
TI  - Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and
      prolongs survival.
AB  - Cancer cachexia is a devastating metabolic syndrome characterized by systemic
      inflammation and massive muscle and adipose tissue wasting. Although it is
      responsible for approximately one-third of cancer deaths, no effective therapies
      are available and the underlying mechanisms have not been fully elucidated. We
      previously identified the bromodomain and extra-terminal domain (BET) protein
      BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET
      inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle
      and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1
      administration dramatically prolongs survival, without directly affecting tumor
      growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly
      promote the muscle atrophy program during cachexia. In addition, BET proteins are
      required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging
      on FoxO3 transcription factor. Overall, these findings indicate that BET proteins
      may represent a promising therapeutic target in the management of cancer
      cachexia.

PMID- 29167429
TI  - Non-universal transmission phase behaviour of a large quantum dot.
AB  - The electron wave function experiences a phase modification at coherent
      transmission through a quantum dot. This transmission phase undergoes a
      characteristic shift of pi when scanning through a Coulomb blockade resonance.
      Between successive resonances either a transmission phase lapse of pi or a phase
      plateau is theoretically expected to occur depending on the parity of quantum dot
      states. Despite considerable experimental effort, this transmission phase
      behaviour has remained elusive for a large quantum dot. Here we report on
      transmission phase measurements across such a large quantum dot hosting hundreds
      of electrons. Scanning the transmission phase along 14 successive resonances with
      an original two-path interferometer, we observe both phase lapses and plateaus.
      We demonstrate that quantum dot deformation alters the sequence of phase lapses
      and plateaus via parity modifications of the involved quantum dot states. Our
      findings set a milestone towards an comprehensive understanding of the
      transmission phase of quantum dots.

PMID- 29167428
TI  - Low pH-induced conformational change and dimerization of sortilin triggers
      endocytosed ligand release.
AB  - Low pH-induced ligand release and receptor recycling are important steps for
      endocytosis. The transmembrane protein sortilin, a beta-propeller containing
      endocytosis receptor, internalizes a diverse set of ligands with roles in cell
      differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand
      release and sortilin recycling are unresolved. Here we present crystal structures
      that show the sortilin luminal segment (s-sortilin) undergoes a conformational
      change and dimerizes at low pH. The conformational change, within all three
      sortilin luminal domains, provides an altered surface and the dimers sterically
      shield a large interface while bringing the two s-sortilin C-termini into close
      proximity. Biophysical and cell-based assays show that members of two different
      ligand families, (pro)neurotrophins and neurotensin, preferentially bind the
      sortilin monomer. This indicates that sortilin dimerization and conformational
      change discharges ligands and triggers recycling. More generally, this work may
      reveal a double mechanism for low pH-induced ligand release by endocytosis
      receptors.

PMID- 29167427
TI  - Scallop genome reveals molecular adaptations to semi-sessile life and
      neurotoxins.
AB  - Bivalve molluscs are descendants of an early-Cambrian lineage superbly adapted to
      benthic filter feeding. Adaptations in form and behavior are well recognized, but
      the underlying molecular mechanisms are largely unknown. Here, we investigate the
      genome, various transcriptomes, and proteomes of the scallop Chlamys farreri, a
      semi-sessile bivalve with well-developed adductor muscle, sophisticated eyes, and
      remarkable neurotoxin resistance. The scallop's large striated muscle is energy
      dynamic but not fully differentiated from smooth muscle. Its eyes are supported
      by highly diverse, intronless opsins expanded by retroposition for broadened
      spectral sensitivity. Rapid byssal secretion is enabled by a specialized foot and
      multiple proteins including expanded tyrosinases. The scallop uses hepatopancreas
      to accumulate neurotoxins and kidney to transform to high-toxicity forms through
      expanded sulfotransferases, probably as deterrence against predation, while it
      achieves neurotoxin resistance through point mutations in sodium channels. These
      findings suggest that expansion and mutation of those genes may have profound
      effects on scallop's phenotype and adaptation.

PMID- 29167430
TI  - Short-term reward experience biases inference despite dissociable neural
      correlates.
AB  - Optimal decision-making employs short-term rewards and abstract long-term
      information based on which of these is deemed relevant. Employing short- vs. long
      term information is associated with different learning mechanisms, yet neural
      evidence showing that these two are dissociable is lacking. Here we demonstrate
      that long-term, inference-based beliefs are biased by short-term reward
      experiences and that dissociable brain regions facilitate both types of learning.
      Long-term inferences are associated with dorsal striatal and frontopolar cortex
      activity, while short-term rewards engage the ventral striatum. Stronger
      concurrent representation of reward signals by mediodorsal striatum and
      frontopolar cortex correlates with less biased, more optimal individual long-term
      inference. Moreover, dynamic modulation of activity in a cortical cognitive
      control network and the medial striatum is associated with trial-by-trial control
      of biases in belief updating. This suggests that counteracting the processing of
      optimally to-be-ignored short-term rewards and cortical suppression of associated
      reward-signals, determines long-term learning success and failure.

PMID- 29167431
TI  - Fabrication and Verification of Conjugated AuNP-Antibody Nanoprobe for
      Sensitivity Improvement in Electrochemical Biosensors.
AB  - This study was designed to obtain covalently coupled conjugates as means for
      achieving higher stability and better coverage of the AuNPs by antibodies on the
      particle surface suitable for sensor performance enhancement. Starting by using a
      modified protocol, colloid gold solution, with mean AuNP core size of ~6 nm was
      synthesized. The protocol used for conjugation of AuNPs to osteocalcin antibody
      in this study relies on covalent and electrostatic attractions between
      constituents. Varieties of conjugates with varying combinations of crosslinkers
      and different concentrations were successfully synthesized. The obtained products
      were characterized and their properties were studied to determine the best
      candidate in sense of antibody - antigen reactivity. Using AuNP-GSH-NHS-Ab
      combination (1:1:1), the tertiary structure of the protein was maintained and
      thus the antibody remained functional in the future steps. This one-pot method
      provided a simple method for covalently coupling antibodies on the particle
      surface while keeping their functionality intact. The AuNP content of the
      solution also accelerated electron transfer rate and thus amplifies the detection
      signal. With the developed and discussed technique herein, a simple solution is
      modeled to be used for measuring serum levels of biomarkers in single and/or
      multiplexed sensor systems.

PMID- 29167432
TI  - Simultaneous quarter-wave plate and half-mirror operation through a highly
      flexible single layer anisotropic metasurface.
AB  - A highly flexible single-layer metasurface manifesting quarter-wave plate as well
      as half-mirror (1:1 beam-splitter) operation in the microwave frequency regime is
      being presented in this research. The designed metasurface reflects half power of
      the impinging linearly polarized electromagnetic wave as circularly polarized
      wave while the remaining half power is transmitted as circularly polarized wave
      at resonance frequency. Similarly, a circularly polarized incident wave is
      reflected and transmitted as linearly polarized wave with equal half powers.
      Moreover, the response of the metasurface is quite stable against the variations
      in the incidence angle up to 45 degrees . The measurements performed on the
      fabricated prototype exhibit a good agreement with the simulation results. The
      compact size, flexible structure, angular stability and two in one operation
      (operating as a quarter-wave plate and beam-splitter at the same time) are the
      main characteristics of the subject metasurface that makes it a potential
      candidate for numerous applications in communication and miniaturized and
      conformal polarization control devices.

PMID- 29167433
TI  - Repeated storage of respired carbon in the equatorial Pacific Ocean over the last
      three glacial cycles.
AB  - As the largest reservoir of carbon exchanging with the atmosphere on glacial
      interglacial timescales, the deep ocean has been implicated as the likely
      location of carbon sequestration during Pleistocene glaciations. Despite strong
      theoretical underpinning for this expectation, radiocarbon data on watermass
      ventilation ages conflict, and proxy interpretations disagree about the depth,
      origin and even existence of the respired carbon pool. Because any change in the
      storage of respiratory carbon is accompanied by corresponding changes in
      dissolved oxygen concentrations, proxy data reflecting oxygenation are valuable
      in addressing these apparent inconsistencies. Here, we present a record of redox
      sensitive uranium from the central equatorial Pacific Ocean to identify intervals
      associated with respiratory carbon storage over the past 350 kyr, providing
      evidence for repeated carbon storage over the last three glacial cycles. We also
      synthesise our data with previous work and propose an internally consistent
      picture of glacial carbon storage and equatorial Pacific Ocean watermass
      structure.

PMID- 29167434
TI  - Overweight in patients with chronic obstructive pulmonary disease needs more
      attention: a cross-sectional study in general practice.
AB  - Guidelines for management of chronic obstructive pulmonary disease (COPD)
      primarily focus on the prevention of weight loss, while overweight and obesity
      are highly prevalent in patients with milder stages of COPD. This cross-sectional
      study examines the association of overweight and obesity with the prevalence of
      comorbid disorders and prescribed medication for obstructive airway disease, in
      patients with mild to moderate COPD. Data were used from electronic health
      records of 380 Dutch general practices in 2014. In total, we identified 4938
      patients with mild or moderate COPD based on spirometry data, and a recorded body
      mass index (BMI) of >=21 kg/m2. Outcomes in overweight (BMI >= 25 and <30 kg/m2)
      and obese (BMI >=30 kg/m2) patients with COPD were compared to those with a
      normal weight (BMI >= 21 and <25 kg/m2), by logistic multilevel analyses.
      Compared to COPD patients with a normal weight, positive associations were found
      for diabetes, osteoarthritis, and hypertension, for both overweight (OR: 1.4-1.7)
      and obese (OR: 2.4-3.8) patients, and for heart failure in obese patients (OR:
      2.3). Osteoporosis was less prevalent in overweight (OR: 0.7) and obese (OR: 0.5)
      patients, and anxiety disorders in obese patients (OR: 0.5). No associations were
      found for coronary heart disease, stroke, sleep disturbance, depression, and
      pneumonia. Furthermore, obese patients were in general more often prescribed
      medication for obstructive airway disease compared to patients with a normal
      weight. The findings of this study underline the need to increase awareness in
      general practitioners for excess weight in patients with mild to moderate COPD.

PMID- 29167435
TI  - Galphai is required for carvedilol-induced beta1 adrenergic receptor beta
      arrestin biased signaling.
AB  - The beta1 adrenergic receptor (beta1AR) is recognized as a classical Galphas
      coupled receptor. Agonist binding not only initiates G protein-mediated signaling
      but also signaling through the multifunctional adapter protein beta-arrestin.
      Some betaAR ligands, such as carvedilol, stimulate betaAR signaling
      preferentially through beta-arrestin, a concept known as beta-arrestin-biased
      agonism. Here, we identify a signaling mechanism, unlike that previously known
      for any Galphas-coupled receptor, whereby carvedilol induces the transition of
      the beta1AR from a classical Galphas-coupled receptor to a Galphai-coupled
      receptor stabilizing a distinct receptor conformation to initiate beta-arrestin
      mediated signaling. Recruitment of Galphai is not induced by any other betaAR
      ligand screened, nor is it required for beta-arrestin-bias activated by the
      beta2AR subtype of the betaAR family. Our findings demonstrate a previously
      unrecognized role for Galphai in beta1AR signaling and suggest that the concept
      of beta-arrestin-bias may need to be refined to incorporate the selective bias of
      receptors towards distinct G protein subtypes.

PMID- 29167436
TI  - Elevated blood pressure is associated with higher prevalence of low visual acuity
      among adolescent males in Northeast China.
AB  - The purpose of this study is to track the trends of low visual acuity (VA) from
      2005 to 2014, and to investigate its associations with systemic blood pressure
      (BP) components among adolescents in Northeast China. A total of 55320 students
      of Han nationality aged 13 to 18 years were included. There has been a
      significant increase in the prevalence of low VA, with 31.3% in 2005, 40.2% in
      2010 and 43.4% in 2014. In multivariable-adjusted logistic regression models,
      each 1-mm Hg increment in systolic BP (SBP) was associated with 0.8% (95%
      confidence interval [CI]: 0.1-1.6%), 0.5% (95% CI: 0.1-0.9%) and 1.1% (95% CI:
      0.6-1.6%) increased odds of low VA for males in 2005, 2010 and 2014; each 1-mm Hg
      increment in pulse pressure (PP) was associated with 1.6% (95% CI: 0.7-2.5%),
      0.8% (95% CI: 0.4-1.2%) and 1.2% (95% CI: 0.7-1.7%) increased odds of low VA.
      Higher PP categories had greater odds for low VA compared with the reference
      group. Similar associations were not observed for females. We conclude that
      higher prevalence of low VA was significantly associated with higher SBP and PP
      in males. Furthermore, there was a dose-dependent association between the
      prevalence of low VA and the levels of PP.

PMID- 29167437
TI  - Structurally triggered metal-insulator transition in rare-earth nickelates.
AB  - Rare-earth nickelates form an intriguing series of correlated perovskite oxides.
      Apart from LaNiO3, they exhibit on cooling a sharp metal-insulator electronic
      phase transition, a concurrent structural phase transition, and a magnetic phase
      transition toward an unusual antiferromagnetic spin order. Appealing for various
      applications, full exploitation of these compounds is still hampered by the lack
      of global understanding of the interplay between their electronic, structural,
      and magnetic properties. Here we show from first-principles calculations that the
      metal-insulator transition of nickelates arises from the softening of an oxygen
      breathing distortion, structurally triggered by oxygen-octahedra rotation
      motions. The origin of such a rare triggered mechanism is traced back in their
      electronic and magnetic properties, providing a united picture. We further
      develop a Landau model accounting for the metal-insulator transition evolution in
      terms of the rare-earth cations and rationalizing how to tune this transition by
      acting on oxygen rotation motions.

PMID- 29167438
TI  - Checkpoint kinase 1 is essential for normal B cell development and
      lymphomagenesis.
AB  - Checkpoint kinase 1 (CHK1) is critical for intrinsic cell cycle control and
      coordination of cell cycle progression in response to DNA damage. Despite its
      essential function, CHK1 has been identified as a target to kill cancer cells and
      studies using Chk1 haploinsufficient mice initially suggested a role as tumor
      suppressor. Here, we report on the key role of CHK1 in normal B-cell development,
      lymphomagenesis and cell survival. Chemical CHK1 inhibition induces BCL2
      regulated apoptosis in primary as well as malignant B-cells and CHK1 expression
      levels control the timing of lymphomagenesis in mice. Moreover, total ablation of
      Chk1 in B-cells arrests their development at the pro-B cell stage, a block that,
      surprisingly, cannot be overcome by inhibition of mitochondrial apoptosis, as
      cell cycle arrest is initiated as an alternative fate to limit the spread of
      damaged DNA. Our findings define CHK1 as essential in B-cell development and
      potent target to treat blood cancer.

PMID- 29167439
TI  - Eroded telomeres are rearranged in quiescent fission yeast cells through
      duplications of subtelomeric sequences.
AB  - While the mechanisms of telomere maintenance has been investigated in dividing
      cells, little is known about the stability of telomeres in quiescent cells and
      how dysfunctional telomeres are processed in non-proliferating cells. Here we
      examine the stability of telomeres in quiescent cells using fission yeast. While
      wild type telomeres are stable in quiescence, we observe that eroded telomeres
      were highly rearranged during quiescence in telomerase minus cells. These
      rearrangements depend on homologous recombination (HR) and correspond to
      duplications of subtelomeric regions. HR is initiated at newly identified
      subtelomeric homologous repeated sequences (HRS). We further show that TERRA
      (Telomeric Repeat-containing RNA) is increased in post-mitotic cells with short
      telomeres and correlates with telomere rearrangements. Finally, we demonstrate
      that rearranged telomeres prevent cells to exit properly from quiescence. Taken
      together, we describe in fission yeast a mode of telomere repair mechanism
      specific to post-mitotic cells that is likely promoted by transcription.

PMID- 29167440
TI  - Fusion guide RNAs for orthogonal gene manipulation with Cas9 and Cpf1.
AB  - The bacteria-derived clustered regularly interspaced short palindromic repeat
      (CRISPR)-Cas systems are powerful tools for genome engineering. Recently, in
      addition to Cas protein engineering, the improvement of guide RNAs are also
      performed, contributing to broadening the research area of CRISPR-Cas9 systems.
      Here we develop a fusion guide RNA (fgRNA) that functions with both Cas9 and Cpf1
      proteins to induce mutations in human cells. Furthermore, we demonstrate that
      fgRNAs can be used in multiplex genome editing and orthogonal genome manipulation
      with two types of Cas proteins. Our results show that fgRNAs can be used as a
      tool for performing multiple gene manipulations.

PMID- 29167441
TI  - Primer synthesis by a eukaryotic-like archaeal primase is independent of its Fe-S
      cluster.
AB  - DNA replication depends on primase, the specialised polymerase responsible for
      synthesis of the RNA primers that are elongated by the replicative DNA
      polymerases. In eukaryotic and archaeal replication, primase is a heterodimer of
      two subunits, PriS and PriL. Recently, a third primase subunit named PriX was
      identified in the archaeon Sulfolobus solfataricus. PriX is essential for primer
      synthesis and is structurally related to the Fe-S cluster domain of eukaryotic
      PriL. Here we show that PriX contains a nucleotide-binding site required for
      primer synthesis, and demonstrate equivalence of nucleotide-binding residues in
      PriX with eukaryotic PriL residues that are known to be important for primer
      synthesis. A primase chimera, where PriX is fused to a truncated version of PriL
      lacking the Fe-S cluster domain retains wild-type levels of primer synthesis. Our
      evidence shows that PriX has replaced PriL as the subunit that endows primase
      with the unique ability to initiate nucleic acid synthesis. Importantly, our
      findings reveal that the Fe-S cluster is not required for primer synthesis.

PMID- 29167442
TI  - Combinatorial metabolic engineering using an orthogonal tri-functional CRISPR
      system.
AB  - Designing an optimal microbial cell factory often requires overexpression, knock
      down, and knock-out of multiple gene targets. Unfortunately, such rewiring of
      cellular metabolism is often carried out sequentially and with low throughput.
      Here, we report a combinatorial metabolic engineering strategy based on an
      orthogonal tri-functional CRISPR system that combines transcriptional activation,
      transcriptional interference, and gene deletion (CRISPR-AID) in the yeast
      Saccharomyces cerevisiae. This strategy enables perturbation of the metabolic and
      regulatory networks in a modular, parallel, and high-throughput manner. We
      demonstrate the application of CRISPR-AID not only to increase the production of
      beta-carotene by 3-fold in a single step, but also to achieve 2.5-fold
      improvement in the display of an endoglucanase on the yeast surface by optimizing
      multiple metabolic engineering targets in a combinatorial manner.

PMID- 29167443
TI  - Drift-dependent changes in iceberg size-frequency distributions.
AB  - Although the size-frequency distributions of icebergs can provide insight into
      how they disintegrate, our understanding of this process is incomplete.
      Fundamentally, there is a discrepancy between iceberg power-law size-frequency
      distributions observed at glacial calving fronts and lognormal size-frequency
      distributions observed globally within open waters that remains unexplained. Here
      we use passive seismic monitoring to examine mechanisms of iceberg disintegration
      as a function of drift. Our results indicate that the shift in the size-frequency
      distribution of iceberg sizes observed is a product of fracture-driven iceberg
      disintegration and dimensional reductions through melting. We suggest that
      changes in the characteristic size-frequency scaling of icebergs can be explained
      by the emergence of a dominant set of driving processes of iceberg degradation
      towards the open ocean. Consequently, the size-frequency distribution required to
      model iceberg distributions accurately must vary according to distance from the
      calving front.

PMID- 29167444
TI  - Publisher Correction: Invisible Trojan-horse attack.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29167445
TI  - Stochastic fluctuations can reveal the feedback signs of gene regulatory networks
      at the single-molecule level.
AB  - Understanding the relationship between spontaneous stochastic fluctuations and
      the topology of the underlying gene regulatory network is of fundamental
      importance for the study of single-cell stochastic gene expression. Here by
      solving the analytical steady-state distribution of the protein copy number in a
      general kinetic model of stochastic gene expression with nonlinear feedback
      regulation, we reveal the relationship between stochastic fluctuations and
      feedback topology at the single-molecule level, which provides novel insights
      into how and to what extent a feedback loop can enhance or suppress molecular
      fluctuations. Based on such relationship, we also develop an effective method to
      extract the topological information of a gene regulatory network from single-cell
      gene expression data. The theory is demonstrated by numerical simulations and,
      more importantly, validated quantitatively by single-cell data analysis of a
      synthetic gene circuit integrated in human kidney cells.

PMID- 29167446
TI  - Hyperpolarized [1-13C]-acetate Renal Metabolic Clearance Rate Mapping.
AB  - 11C-acetate is a positron emission tomography (PET) tracer of oxidative
      metabolism, whereas hyperpolarized 13C-acetate can be used in magnetic resonance
      imaging (MRI) for investigating specific metabolic processes. The aims of this
      study were to examine if the kinetic formalism of 11C-acetate PET in the kidneys
      is comparable to that of 13C-acetate MRI, and to compare the dynamic metabolic
      information of hyperpolarized 13C-acetate MRI with that obtained with 11C-acetate
      PET. Rats were examined with dynamic hyperpolarized 13C-acetate MRI or 11C
      acetate PET before and after intravenous injection of furosemide, a loop diuretic
      known to alter both the hemodynamics and oxygen consumption in the kidney. The
      metabolic clearance rates (MCR) were estimated and compared between the two
      modalities experimentally in vivo and in simulations. There was a clear
      dependency on the mean transit time and MCR for both 13C-acetate and 11C-acetate
      following furosemide administration, while no dependencies on the apparent renal
      perfusion were observed. This study demonstrated that hyperpolarized 13C-acetate
      MRI is feasible for measurements of the intrarenal energetic demand via the MCR,
      and that the quantitative measures are correlated with those measured by 11C
      acetate PET, even though the temporal window is more than 30 times longer with
      11C-acetate.

PMID- 29167447
TI  - Hyperoxidation of ether-linked phospholipids accelerates neutrophil extracellular
      trap formation.
AB  - Because neutrophil extracellular trap (NET) formation is involved in the
      pathology of a wide variety of diseases, NET-regulating compounds are expected to
      be useful for the therapies of these diseases. In this study, we identified
      sulfasalazine (SSZ) as a potent enhancer of NET formation both in vitro and in
      vivo. Although SSZ did not increase the amount of ROS generated, it accelerated
      the generation of ether-linked oxidized phospholipids, such as PE (18;1e/15-HETE)
      and PC (16;0e/13-HODE). Trolox, but not 2-ME, effectively suppressed lipid
      oxidation and NET formation that were induced by SSZ. SSZ is known as a potent
      inducer of ferroptosis in cancer cells by inhibiting xCT, a component of the
      cystine transporter. However, we found that SSZ accelerated NET formation in an
      xCT-independent manner. Structure-activity relationship studies revealed that the
      sulfapyridine moiety of SSZ plays a central role in enhancing NET formation.
      Furthermore, we found that two additional sulfonamide and sulfone derivatives
      possess NET-inducing activity by accelerating lipid oxidation. These results
      indicate that the hyperoxidation of ether-linked phospholipids is a key mechanism
      for accelerating NET formation.

PMID- 29167448
TI  - Systematic Screening of Chemokines to Identify Candidates to Model and Create
      Ectopic Lymph Node Structures for Cancer Immunotherapy.
AB  - The induction of ectopic lymph node structures (ELNs) holds great promise to
      augment immunotherapy against multiple cancers including metastatic melanoma, in
      which ELN formation has been associated with a unique immune-related gene
      expression signature composed of distinct chemokines. To investigate the
      therapeutic potential of ELNs induction, preclinical models of ELNs are needed
      for interrogation of these chemokines. Computational models provide a non
      invasive, cost-effective method to investigate leukocyte trafficking in the tumor
      microenvironment, but parameterizing such models is difficult due to differing
      assay conditions and contexts among the literature. To better achieve this, we
      systematically performed microchemotaxis assays on purified immune subsets
      including human pan-T cells, CD4+ T cells, CD8+ T cells, B cells, and NK cells,
      with 49 recombinant chemokines using a singular technique, and standardized
      conditions resulting in a dataset representing 238 assays. We then outline a
      groundwork computational model that can simulate cellular migration in the tumor
      microenvironment in response to a chemoattractant gradient created from stromal,
      lymphoid, or antigen presenting cell interactions. The resulting model can then
      be parameterized with standardized data, such as the dataset presented here, and
      demonstrates how a computational approach can help elucidate developing ELNs and
      their impact on tumor progression.

PMID- 29167449
TI  - Structure of human immunoproteasome with a reversible and noncompetitive
      inhibitor that selectively inhibits activated lymphocytes.
AB  - Proteasome inhibitors benefit patients with multiple myeloma and B cell-dependent
      autoimmune disorders but exert toxicity from inhibition of proteasomes in other
      cells. Toxicity should be minimized by reversible inhibition of the
      immunoproteasome beta5i subunit while sparing the constitutive beta5c subunit.
      Here we report beta5i-selective inhibition by asparagine-ethylenediamine (AsnEDA)
      based compounds and present the high-resolution cryo-EM structural analysis of
      the human immunoproteasome. Despite inhibiting noncompetitively, an AsnEDA
      inhibitor binds the active site. Hydrophobic interactions are accompanied by
      hydrogen bonding with beta5i and beta6 subunits. The inhibitors are far more
      cytotoxic for myeloma and lymphoma cell lines than for hepatocarcinoma or non
      activated lymphocytes. They block human B-cell proliferation and promote
      apoptotic cell death selectively in antibody-secreting B cells, and to a lesser
      extent in activated human T cells. Reversible, beta5i-selective inhibitors may be
      useful for treatment of diseases involving activated or neoplastic B cells or
      activated T cells.

PMID- 29167451
TI  - The role of Atlantic overturning circulation in the recent decline of Atlantic
      major hurricane frequency.
AB  - Observed Atlantic major hurricane frequency has exhibited pronounced multidecadal
      variability since the 1940s. However, the cause of this variability is debated.
      Using observations and a coupled earth system model (GFDL-ESM2G), here we show
      that the decline of the Atlantic major hurricane frequency during 2005-2015 is
      associated with a weakening of the Atlantic Meridional Overturning Circulation
      (AMOC) inferred from ocean observations. Directly observed North Atlantic sulfate
      aerosol optical depth has not increased (but shows a modest decline) over this
      period, suggesting the decline of the Atlantic major hurricane frequency during
      2005-2015 is not likely due to recent changes in anthropogenic sulfate aerosols.
      Instead, we find coherent multidecadal variations involving the inferred AMOC and
      Atlantic major hurricane frequency, along with indices of Atlantic Multidecadal
      Variability and inverted vertical wind shear. Our results provide evidence for an
      important role of the AMOC in the recent decline of Atlantic major hurricane
      frequency.

PMID- 29167450
TI  - MafB is a critical regulator of complement component C1q.
AB  - The transcription factor MafB is expressed by monocytes and macrophages.
      Efferocytosis (apoptotic cell uptake) by macrophages is important for inhibiting
      the development of autoimmune diseases, and is greatly reduced in Mafb-deficient
      macrophages. Here, we show the expression of the first protein in the classical
      complement pathway C1q is important for mediating efferocytosis and is reduced in
      Mafb-deficient macrophages. The efferocytosis defect in Mafb-deficient
      macrophages can be rescued by adding serum from wild-type mice, but not by adding
      serum from C1q-deficient mice. By hemolysis assay we also show that activation of
      the classical complement pathway is decreased in Mafb-deficient mice. In
      addition, MafB overexpression induces C1q-dependent gene expression and signals
      that induce C1q genes are less effective in the absence of MafB. We also show
      that Mafb-deficiency can increase glomerular autoimmunity, including anti-nuclear
      antibody deposition. These results show that MafB is an important regulator of
      C1q.

PMID- 29167453
TI  - Author Correction: A Fluctuation Equation of State for Prediction of High
      Pressure Densities of Ionic Liquids.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29167452
TI  - Cross continental increase in methane ebullition under climate change.
AB  - Methane (CH4) strongly contributes to observed global warming. As natural CH4
      emissions mainly originate from wet ecosystems, it is important to unravel how
      climate change may affect these emissions. This is especially true for ebullition
      (bubble flux from sediments), a pathway that has long been underestimated but
      generally dominates emissions. Here we show a remarkably strong relationship
      between CH4 ebullition and temperature across a wide range of freshwater
      ecosystems on different continents using multi-seasonal CH4 ebullition data from
      the literature. As these temperature-ebullition relationships may have been
      affected by seasonal variation in organic matter availability, we also conducted
      a controlled year-round mesocosm experiment. Here 4  degrees C warming led to 51%
      higher total annual CH4 ebullition, while diffusion was not affected. Our
      combined findings suggest that global warming will strongly enhance freshwater
      CH4 emissions through a disproportional increase in ebullition (6-20% per 1 
      degrees C increase), contributing to global warming.

PMID- 29167454
TI  - NR4A1 inhibition synergizes with ibrutinib in killing mantle cell lymphoma cells.

PMID- 29167455
TI  - Intelligence is associated with the modular structure of intrinsic brain
      networks.
AB  - General intelligence is a psychological construct that captures in a single
      metric the overall level of behavioural and cognitive performance in an
      individual. While previous research has attempted to localise intelligence in
      circumscribed brain regions, more recent work focuses on functional interactions
      between regions. However, even though brain networks are characterised by
      substantial modularity, it is unclear whether and how the brain's modular
      organisation is associated with general intelligence. Modelling subject-specific
      brain network graphs from functional MRI resting-state data (N = 309), we found
      that intelligence was not associated with global modularity features (e.g.,
      number or size of modules) or the whole-brain proportions of different node types
      (e.g., connector hubs or provincial hubs). In contrast, we observed
      characteristic associations between intelligence and node-specific measures of
      within- and between-module connectivity, particularly in frontal and parietal
      brain regions that have previously been linked to intelligence. We propose that
      the connectivity profile of these regions may shape intelligence-relevant aspects
      of information processing. Our data demonstrate that not only region-specific
      differences in brain structure and function, but also the network-topological
      embedding of fronto-parietal as well as other cortical and subcortical brain
      regions is related to individual differences in higher cognitive abilities, i.e.,
      intelligence.

PMID- 29167456
TI  - Warming, shading and a moth outbreak reduce tundra carbon sink strength
      dramatically by changing plant cover and soil microbial activity.
AB  - Future increases in temperature and cloud cover will alter plant growth and
      decomposition of the large carbon pools stored in Arctic soils. A better
      understanding of interactions between above- and belowground processes and
      communities of plants and microorganisms is essential for predicting Arctic
      ecosystem responses to climate change. We measured ecosystem CO2 fluxes during
      the growing season for seven years in a dwarf-shrub tundra in West Greenland
      manipulated with warming and shading and experiencing a natural larvae outbreak.
      Vegetation composition, soil fungal community composition, microbial activity,
      and nutrient availability were analyzed after six years of treatment. Warming and
      shading altered the plant community, reduced plant CO2 uptake, and changed fungal
      community composition. Ecosystem carbon accumulation decreased during the growing
      season by 61% in shaded plots and 51% in warmed plots. Also, plant recovery was
      reduced in both manipulations following the larvae outbreak during the fifth
      treatment year. The reduced plant recovery in manipulated plots following the
      larvae outbreak suggests that climate change may increase tundra ecosystem
      sensitivity to disturbances. Also, plant community changes mediated via reduced
      light and reduced water availability due to increased temperature can strongly
      lower the carbon sink strength of tundra ecosystems.

PMID- 29167457
TI  - The genetic basis for the adaptation of E. coli to sugar synthesis from CO2.
AB  - Understanding the evolution of a new metabolic capability in full mechanistic
      detail is challenging, as causative mutations may be masked by non-essential
      "hitchhiking" mutations accumulated during the evolutionary trajectory. We have
      previously used adaptive laboratory evolution of a rationally engineered ancestor
      to generate an Escherichia coli strain able to utilize CO2 fixation for sugar
      synthesis. Here, we reveal the genetic basis underlying this metabolic
      transition. Five mutations are sufficient to enable robust growth when a non
      native Calvin-Benson-Bassham cycle provides all the sugar-derived metabolic
      building blocks. These mutations are found either in enzymes that affect the
      efflux of intermediates from the autocatalytic CO2 fixation cycle toward biomass
      (prs, serA, and pgi), or in key regulators of carbon metabolism (crp and ppsR).
      Using suppressor analysis, we show that a decrease in catalytic capacity is a
      common feature of all mutations found in enzymes. These findings highlight the
      enzymatic constraints that are essential to the metabolic stability of
      autocatalytic cycles and are relevant to future efforts in constructing non
      native carbon fixation pathways.

PMID- 29167458
TI  - Assembly of CRISPR ribonucleoproteins with biotinylated oligonucleotides via an
      RNA aptamer for precise gene editing.
AB  - Writing specific DNA sequences into the human genome is challenging with non
      viral gene-editing reagents, since most of the edited sequences contain various
      imprecise insertions or deletions. We developed a modular RNA aptamer
      streptavidin strategy, termed S1mplex, to complex CRISPR-Cas9 ribonucleoproteins
      with a nucleic acid donor template, as well as other biotinylated molecules such
      as quantum dots. In human cells, tailored S1mplexes increase the ratio of
      precisely edited to imprecisely edited alleles up to 18-fold higher than standard
      gene-editing methods, and enrich cell populations containing multiplexed precise
      edits up to 42-fold. These advances with versatile, preassembled reagents could
      greatly reduce the time and cost of in vitro or ex vivo gene-editing applications
      in precision medicine and drug discovery and aid in the development of increased
      and serial dosing regimens for somatic gene editing in vivo.

PMID- 29167459
TI  - ZIKV infection regulates inflammasomes pathway for replication in monocytes.
AB  - ZIKV causes microcephaly by crossing the placental barrier, however, the
      mechanism of trans-placental dissemination of ZIKV remains unknown. Here, we
      sought to determine whether monocytes, which can cross tissue barriers, assist
      ZIKV dissemination to the fetus. We determined this by infecting monocytes with
      two strains of ZIKV: South American (PRVABC59) and Nigerian (IBH30656) and
      analyzing viral replication. We found that ZIKV infects and replicates in
      monocytes and macrophages, which results in the modulation of a large number of
      cellular genes. Analysis of these genes identified multiple pathways including
      inflammasome to be targeted by ZIKV, which was confirmed by analyzing the
      transcript levels of the proteins of inflammasome pathways, NLRP3, ASC, caspase
      1, IL-1 and IL-18. Interestingly, IFNalpha and the IFN inducible gene, MxA were
      not enhanced, suggesting prevention of innate antiviral defense by ZIKV. Also,
      inhibition of inflammasome led to an increased transcriptional activity of
      IFNalpha, MxA and CXCL10. Based on these results we suggest that ZIKV
      transcription is regulated by inflammasomes.

PMID- 29167460
TI  - Early vaccination protects against childhood leukemia: A systematic review and
      meta-analysis.
AB  - Leukemia is the most commonly diagnosed childhood cancer, although its etiology
      is still largely unknown. Growing evidence supports a role for infection in the
      etiology of acute lymphocytic leukemia (ALL), and the involvement of the immune
      system suggests that vaccination may also play a role. However, the findings
      presented in the published literature are inconsistent. Therefore, we conducted a
      PRISMA systematic review and meta-analysis. 14 studies were identified and meta
      analyzed. Vaccinations studied comprised Bacillus Calmette-Guerin (BCG) vaccine,
      Triple vaccine, Hepatitis B vaccine (HBV), Polio, Measles, Rubella, Mumps,
      trivalent MMR vaccine and Haemophilus influenza type B (HiB) vaccine. We observed
      a protective association between any vaccination in the first year of life and
      risk of childhood leukemia (summary odds ratio (OR) 0.58 [95% confidence interval
      (CI) 0.36-0.91]). When individual vaccines were analysed, some evidence of an
      association was seen only for BCG (summary OR 0.73 [95% CI 0.50-1.08]). In
      conclusion, early vaccination appears to be associated with a reduced risk of
      childhood leukemia. This finding may be underpinned by the association observed
      for BCG. Given the relatively imprecise nature of the results of this meta
      analysis, our findings should be interpreted cautiously and replicated in future
      studies.

PMID- 29167461
TI  - New Description of Evolution of Magnetic Phases in Artificial Honeycomb Lattice.
AB  - Artificial magnetic honeycomb lattice provides a two-dimensional archetypal
      system to explore novel phenomena of geometrically frustrated magnets. According
      to theoretical reports, an artificial magnetic honeycomb lattice is expected to
      exhibit several phase transitions to unique magnetic states as a function of
      reducing temperature. Experimental investigations of permalloy artificial
      honeycomb lattice of connected ultra-small elements, [Formula: see text] 12 nm,
      reveal a more complicated behavior. First, upon cooling the sample to
      intermediate temperature, [Formula: see text] 175 K, the system manifests a non
      unique state where the long range order co-exists with short-range magnetic
      charge order and weak spin ice state. Second, at much lower temperature,
      [Formula: see text] 6 K, the long-range spin solid state exhibits a re-entrant
      behavior. Both observations are in direct contrast to the present understanding
      of this system. New theoretical approaches are needed to develop a comprehensive
      formulation of this two dimensional magnet.

PMID- 29167462
TI  - Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage
      sensing and pore opening.
AB  - In voltage-activated ion channels, voltage sensor (VSD) activation induces pore
      opening via VSD-pore coupling. Previous studies show that the pore in KCNQ1
      channels opens when the VSD activates to both intermediate and fully activated
      states, resulting in the intermediate open (IO) and activated open (AO) states,
      respectively. It is also well known that accompanying KCNQ1 channel opening, the
      ionic current is suppressed by a rapid process called inactivation. Here we show
      that inactivation of KCNQ1 channels derives from the different mechanisms of the
      VSD-pore coupling that lead to the IO and AO states, respectively. When the VSD
      activates from the intermediate state to the activated state, the VSD-pore
      coupling has less efficacy in opening the pore, producing inactivation. These
      results indicate that different mechanisms, other than the canonical VSD-pore
      coupling, are at work in voltage-dependent ion channel activation.

PMID- 29167463
TI  - Structural insights into the committed step of bacterial phospholipid
      biosynthesis.
AB  - The membrane-integral glycerol 3-phosphate (G3P) acyltransferase PlsY catalyses
      the committed and essential step in bacterial phospholipid biosynthesis by
      acylation of G3P, forming lysophosphatidic acid. It contains no known
      acyltransferase motifs, lacks eukaryotic homologs, and uses the unusual acyl
      phosphate as acyl donor, as opposed to acyl-CoA or acyl-carrier protein for other
      acyltransferases. Previous studies have identified several PlsY inhibitors as
      potential antimicrobials. Here we determine the crystal structure of PlsY at 1.48
      A resolution, revealing a seven-transmembrane helix fold. Four additional
      substrate- and product-bound structures uncover the atomic details of its
      relatively inflexible active site. Structure and mutagenesis suggest a different
      acylation mechanism of 'substrate-assisted catalysis' that, unlike other
      acyltransferases, does not require a proteinaceous catalytic base to complete.
      The structure data and a high-throughput enzymatic assay developed in this work
      should prove useful for virtual and experimental screening of inhibitors against
      this vital bacterial enzyme.

PMID- 29167464
TI  - North Atlantic variability and its links to European climate over the last 3000
      years.
AB  - The subpolar North Atlantic is a key location for the Earth's climate system. In
      the Labrador Sea, intense winter air-sea heat exchange drives the formation of
      deep waters and the surface circulation of warm waters around the subpolar gyre.
      This process therefore has the ability to modulate the oceanic northward heat
      transport. Recent studies reveal decadal variability in the formation of Labrador
      Sea Water. Yet, crucially, its longer-term history and links with European
      climate remain limited. Here we present new decadally resolved marine proxy
      reconstructions, which suggest weakened Labrador Sea Water formation and gyre
      strength with similar timing to the centennial cold periods recorded in
      terrestrial climate archives and historical records over the last 3000 years.
      These new data support that subpolar North Atlantic circulation changes, likely
      forced by increased southward flow of Arctic waters, contributed to modulating
      the climate of Europe with important societal impacts as revealed in European
      history.

PMID- 29167466
TI  - Mussel larvae modify calcifying fluid carbonate chemistry to promote
      calcification.
AB  - Understanding mollusk calcification sensitivity to ocean acidification (OA)
      requires a better knowledge of calcification mechanisms. Especially in rapidly
      calcifying larval stages, mechanisms of shell formation are largely unexplored
      yet these are the most vulnerable life stages. Here we find rapid generation of
      crystalline shell material in mussel larvae. We find no evidence for
      intracellular CaCO3 formation, indicating that mineral formation could be
      constrained to the calcifying space beneath the shell. Using microelectrodes we
      show that larvae can increase pH and [CO32-] beneath the growing shell, leading
      to a ~1.5-fold elevation in calcium carbonate saturation state (Omegaarag).
      Larvae exposed to OA exhibit a drop in pH, [CO32-] and Omegaarag at the site of
      calcification, which correlates with decreased shell growth, and, eventually,
      shell dissolution. Our findings help explain why bivalve larvae can form shells
      under moderate acidification scenarios and provide a direct link between ocean
      carbonate chemistry and larval calcification rate.

PMID- 29167465
TI  - Coupling of Polo kinase activation to nuclear localization by a bifunctional NLS
      is required during mitotic entry.
AB  - The Polo kinase is a master regulator of mitosis and cytokinesis conserved from
      yeasts to humans. Polo is composed of an N-term kinase domain (KD) and a C-term
      polo-box domain (PBD), which regulates its subcellular localizations. The PBD and
      KD can interact and inhibit each other, and this reciprocal inhibition is
      relieved when Polo is phosphorylated at its activation loop. How Polo activation
      and localization are coupled during mitotic entry is unknown. Here we report that
      PBD binding to the KD masks a nuclear localization signal (NLS). Activating
      phosphorylation of the KD leads to exposure of the NLS and entry of Polo into the
      nucleus before nuclear envelope breakdown. Failures of this mechanism result in
      misregulation of the Cdk1-activating Cdc25 phosphatase and lead to mitotic and
      developmental defects in Drosophila. These results uncover spatiotemporal
      mechanisms linking master regulatory enzymes during mitotic entry.

PMID- 29167467
TI  - Chinese CO2 emission flows have reversed since the global financial crisis.
AB  - This study seeks to estimate the carbon implications of recent changes in China's
      economic development patterns and role in global trade in the post-financial
      crisis era. We utilised the latest socioeconomic datasets to compile China's 2012
      multiregional input-output (MRIO) table. Environmentally extended input-output
      analysis and structural decomposition analysis (SDA) were applied to investigate
      the driving forces behind changes in CO2 emissions embodied in China's domestic
      and foreign trade from 2007 to 2012. Here we show that emission flow patterns
      have changed greatly in both domestic and foreign trade since the financial
      crisis. Some economically less developed regions, such as Southwest China, have
      shifted from being a net emission exporter to being a net emission importer. In
      terms of foreign trade, emissions embodied in China's exports declined from 2007
      to 2012 mainly due to changes in production structure and efficiency gains, while
      developing countries became the major destination of China's export emissions.

PMID- 29167468
TI  - Transcriptome and metabolite analyses reveal the complex metabolic genes involved
      in volatile terpenoid biosynthesis in garden sage (Salvia officinalis).
AB  - A large number of terpenoid compounds have been extracted from different tissues
      of S. officinalis. However, the molecular genetic basis of terpene biosynthesis
      pathways is virtually unknown. In this study, approximately 6.6 Gb of raw data
      were generated from the transcriptome of S. officinalis leaves using Illumina
      HiSeq 2000 sequencing. After filtering and removing the adapter sequences from
      the raw data, the number of reads reached 21 million, comprising 98 million of
      high-quality nucleotide bases. 48,671 unigenes were assembled de novo and
      annotated for establishing a valid database for studying terpenoid biosynthesis.
      We identified 135 unigenes that are putatively involved in terpenoid metabolism,
      including 70 mevalonate and methyl-erythritol phosphate pathways, terpenoid
      backbone biosynthesis genes, and 65 terpene synthase genes. Moreover, five
      terpene synthase genes were studied for their functions in terpenoid biosynthesis
      by using transgenic tobacco; most transgenic tobacco plants expressing these
      terpene synthetic genes produced increased amounts of terpenoids compared with
      wild-type control. The combined data analyses from the transcriptome and
      metabolome provide new insights into our understanding of the complex metabolic
      genes in terpenoid-rich sage, and our study paves the way for the future
      metabolic engineering of the biosynthesis of useful terpene compounds in S.
      officinalis.

PMID- 29167469
TI  - Baseline and Breakthrough Resistance Mutations in HCV Patients Failing DAAs.
AB  - Sustained virologic response rates have increased dramatically following direct
      acting antiviral (DAA) therapy in chronic HCV infection. However, resistance
      associated substitutions (RASs) may occur either prior to DAA or following drug
      exposure. The aim of this study was to determine RASs in DAA treatment-failing
      patients and the role of RASs in failure treatment. Six hundred and twenty HCV
      patients were evaluated. Direct sequencing of HCV genes was performed at
      breakthrough in all 31 patients failing DAAs, and in 19 baseline patients. Deep
      sequencing analysis was performed in 15/19 baseline patients. RASs were detected
      at breakthrough in 17/31 patients and at baseline in 11/19 patients, although,
      only 8/19 patients carried RASs associated with the prescribed regimen. Deep
      sequencing analysis showed RASs at baseline in 10/15 treatment-failing patients.
      No significant difference was observed with the Sanger sequencing. Treatment
      failure in the 14/31 patients without RASs was associated with suboptimal
      treatment. In 54.8% of treatment-failing patients one of the causes of failure
      might be the presence of RASs. In the majority of patients with RASs, mutations
      were present at baseline. Direct resistance test is advocated before treatment
      and at breakthrough in order to optimize retreatment regimens.

PMID- 29167470
TI  - Glucagon-like peptide-1 mimetics, optimal for Asian type 2 diabetes patients with
      and without overweight/obesity: meta-analysis of randomized controlled trials.
AB  - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are desirable for diabetes,
      especially in patients with overweight/obesity. We aimed to determine whether GLP
      1RAs exhibit different glucose-lowering efficacies between Asian type 2 diabetes
      (T2D) patients with and without overweight/obesity. Randomized controlled trials
      were searched in EMBASE, MEDLINE, CENTRAL, and ClinicalTrials.gov. Studies
      published in English with treatment duration >=12 weeks and information on HbA1c
      changes were included. The studies were divided into normal body mass index (BMI)
      and overweight/obese groups according to baseline BMI. Among 3190 searched
      studies, 20 trials were included in the meta-analysis. The standardized mean
      differences in HbA1c change, fasting glucose change, and postprandial glucose
      change were equivalent between normal BMI and overweight/obese studies (p >
      0.05). The relative risk of HbA1c < 6.5% target achievement in normal BMI trials
      (7.93; 95% confidence interval: 3.27, 19.20) was superior to that in
      overweight/obesity trials (2.23; 1.67, 2.97), with a significant difference (p =
      0.020). Body weight loss (p = 0.572) and hypoglycemic risk(p = 0.920) were
      similar in the two groups. The glucose-lowering effects of GLP-1RAs were
      equivalent among Asian T2D patients. With their advantages for weight-loss or
      weight-maintenance, GLP-1RAs are optimal medicines for Asian T2D patients with
      and without overweight/obesity.

PMID- 29167472
TI  - Two opposite size effects of hardness at real nano-scale and their distinct
      origins.
AB  - Although it has been well known that hardness of metals obtained with conical
      indenter remains a constant of about 3 times yield strength in conventional
      tests, and hardness will show a size effect of increasing hardness with
      decreasing indentation depth in micro-scale beyond 100 nm, the nano-indentation
      hardness experiments within 100 nm indentation depth usually show a large
      deviation and unclear trends. We report the cross-validated experimental and
      numerical results of two opposite depth-dependences of hardness at real nano
      scale. That is to say, the indentation size effect (ISE) of hardness of single
      crystal copper shows a rapid increase and then a slow decrease with increasing
      indentation depth within 100 nm depth. All of the results were coss-checked by
      means of both elaborated nano-indentation experiments with calibrated indenter
      tips and large scale molecular dynamics (MD) simulations. Further analysis of the
      MD results and experimental data reveal that the two opposite ISE of nano
      hardness should be attributed to the finite roundness of the indenter tip and the
      intrinsic transition governing property of the material.

PMID- 29167471
TI  - Pim-3 as a potential predictor of chemoradiotherapy resistance in locally
      advanced rectal cancer patients.
AB  - Approximately 30% of locally advanced rectal cancer patients might not benefit
      from chemoradiotherapy; however, the response to neoadjuvant chemoradiotherapy in
      these cases is difficult to predict. Pim-3 is a member of the provirus
      integration site for a moloney murine leukemia virus family of proteins that
      contributes to cell proliferation, survival, and chemotherapy resistance.
      Therefore, the relationship between Pim-3 expression and response to neoadjuvant
      chemoradiotherapy in rectal cancer patients is important to evaluate. 175 rectal
      cancer patients who underwent neoadjuvant treatment enrolled in this study. The
      relationship between Pim-3 expression on immunohistochemical analysis of rectal
      cancer tissue, which was obtained before treatment, the response to
      chemoradiotherapy and survival was investigated. The patients with no Pim-3
      expression were more likely to achieve a pathologic complete response to
      chemoradiotherapy than patients with Pim-3 expression (P = 0.001). Cox
      multivariate analysis showed that the significant prognostic factors were Pim-3
      expression (P = 0.003) and the number of neoadjuvant chemotherapy cycles (P =
      0.005) for overall survival. Neoadjuvant chemotherapy cycles (P = 0.007),
      adjuvant chemotherapy cycles (P = 0.004) and pathology types (P = 0.049) were
      significant prognostic factors for disease-free survival. Pim-3 is a potential
      predictive biomarker for the response of rectal cancer to chemoradiotherapy.

PMID- 29167473
TI  - Two-Dimensional Co2S2 monolayer with robust ferromagnetism.
AB  - Design and synthesis of two-dimensional (2D) materials with robust intrinsic
      ferromagnetism is highly desirable due to their potential applications in
      spintronics devices. In this work, we identify a new 2D cobalt sulfide (Co2S2)
      material by using first-principles calculations and particle swarm optimization
      (PSO) global structure search. We show that the 2D Co2S2 is most stable in the
      litharge type tetragonal structure with space group of P4/nmm. The elastic
      constants, phonon spectrum, and molecular dynamics simulation confirm its
      mechanical, dynamical and thermal stability, respectively. It is also found that
      Co2S2 monolayer is a ferromagnetic metal with a Curie temperature up to 404 K. In
      addition, we propose a feasible procedure to synthesize the Co2S2 monolayer by
      chemically exfoliating from bulk TlCo2S2 phase.

PMID- 29167474
TI  - Tuning the Composition and Structure of Amorphous Molybdenum Sulfide/Carbon Black
      Nanocomposites by Radiation Technique for Highly Efficient Hydrogen Evolution.
AB  - Amorphous molybdenum sulfide/carbon black (MoSx/C) nanocomposites are synthesized
      by a facile one-step gamma-ray radiation induced reduction process. Amorphous
      MoSx shows better intrinsic activity than crystalline MoS2. And the composition
      and amorphous structure of MoSx could be expediently tuned by absorbed dose for
      excellent catalytic activity. Meanwhile, the addition of carbon black leads to a
      significant decrease of charge transfer resistance and increase of active sites
      of MoSx/C composite. Consequently, MoSx/C nanocomposite shows Pt-like catalytic
      activity towards hydrogen evolution reaction (HER), which requires an onset over
      potential of 40 mV and over potential of 76 mV to achieve a current density of 10
      mA cm-2, and the corresponding Tafel slope is 48 mV decade-1. After 6000 CV
      cycles, the catalytic activity of MoSx/C shows no obvious decrease. However, when
      platinum (Pt) foil is used as counter electrode, MoSx/C composite show better
      catalytic activity abnormally after long-term cycling tests. The dissolution of
      Pt was observed in HER and the Pt dissolution mechanism is elucidated by further
      analyzing the surface composition of after-cycling electrodes, which offers
      highly valuable guidelines for using Pt electrode in HER.

PMID- 29167475
TI  - Correlation between tunability and anisotropy in magnetoelectric voltage tunable
      inductor (VTI).
AB  - Electric field modulation of magnetic properties via magnetoelectric coupling in
      composite materials is of fundamental and technological importance for realizing
      tunable energy efficient electronics. Here we provide foundational analysis on
      magnetoelectric voltage tunable inductor (VTI) that exhibits extremely large
      inductance tunability of up to 1150% under moderate electric fields. This field
      dependence of inductance arises from the change of permeability, which correlates
      with the stress dependence of magnetic anisotropy. Through combination of
      analytical models that were validated by experimental results, comprehensive
      understanding of various anisotropies on the tunability of VTI is provided.
      Results indicate that inclusion of magnetic materials with low magnetocrystalline
      anisotropy is one of the most effective ways to achieve high VTI tunability. This
      study opens pathway towards design of tunable circuit components that exhibit
      field-dependent electronic behavior.

PMID- 29167476
TI  - Levodopa-induced abnormal involuntary movements correlate with altered
      permeability of the blood-brain-barrier in the basal ganglia.
AB  - Chronic levodopa treatment leads to the appearance of dyskinesia in the majority
      of Parkinson's disease patients. Neurovascular dysregulation in putaminal and
      pallidal regions is thought to be an underlying feature of this complication of
      treatment. We used microPET to study unilaterally lesioned 6-hydroxydopamine rats
      that developed levodopa-induced abnormal involuntary movements (AIMs) after three
      weeks of drug treatment. Animals were scanned with [15O]-labeled water and [18F]
      fluorodeoxyglucose, to map regional cerebral blood flow and glucose metabolism,
      and with [11C]-isoaminobutyric acid (AIB), to assess blood-brain-barrier (BBB)
      permeability, following separate injections of levodopa or saline. Multitracer
      scan data were acquired in each animal before initiating levodopa treatment, and
      again following the period of daily drug administration. Significant dissociation
      of vasomotor and metabolic levodopa responses was seen in the striatum/globus
      pallidus (GP) of the lesioned hemisphere. These changes were accompanied by
      nearby increases in [11C]-AIB uptake in the ipsilateral GP, which correlated with
      AIMs scores. Histopathological analysis revealed high levels of microvascular
      nestin immunoreactivity in the same region. The findings demonstrate that
      regional flow-metabolism dissociation and increased BBB permeability are
      simultaneously induced by levodopa within areas of active microvascular
      remodeling, and that such changes correlate with the severity of dyskinesia.

PMID- 29167477
TI  - Heterolytic Splitting of Molecular Hydrogen by Frustrated and Classical Lewis
      Pairs: A Unified Reactivity Concept.
AB  - Using a set of state-of-the-art quantum chemical techniques we scrutinized the
      characteristically different reactivity of frustrated and classical Lewis pairs
      towards molecular hydrogen. The mechanisms and reaction profiles computed for the
      H2 splitting reaction of various Lewis pairs are in good agreement with the
      experimentally observed feasibility of H2 activation. More importantly, the
      analysis of activation parameters unambiguously revealed the existence of two
      reaction pathways through a low-energy and a high-energy transition state. An
      exhaustive scrutiny of these transition states, including their stability,
      geometry and electronic structure, reflects that the electronic rearrangement in
      low-energy transition states is fundamentally different from that of high-energy
      transition states. Our findings reveal that the widespread consensus mechanism of
      H2 splitting characterizes activation processes corresponding to high-energy
      transition states and, accordingly, is not operative for H2-activating systems.
      One of the criteria of H2-activation, actually, is the availability of a low
      energy transition state that represents a different H2 splitting mechanism, in
      which the electrostatic field generated in the cavity of Lewis pair plays a
      critical role: to induce a strong polarization of H2 that facilities an efficient
      end-on acid-H2 interaction and to stabilize the charge separated "H+-H-" moiety
      in the transition state.

PMID- 29167478
TI  - An Evolutionary Game Theory Model of Spontaneous Brain Functioning.
AB  - Our brain is a complex system of interconnected regions spontaneously organized
      into distinct networks. The integration of information between and within these
      networks is a continuous process that can be observed even when the brain is at
      rest, i.e. not engaged in any particular task. Moreover, such spontaneous
      dynamics show predictive value over individual cognitive profile and constitute a
      potential marker in neurological and psychiatric conditions, making its
      understanding of fundamental importance in modern neuroscience. Here we present a
      theoretical and mathematical model based on an extension of evolutionary game
      theory on networks (EGN), able to capture brain's interregional dynamics by
      balancing emulative and non-emulative attitudes among brain regions. This results
      in the net behavior of nodes composing resting-state networks identified using
      functional magnetic resonance imaging (fMRI), determining their moment-to-moment
      level of activation and inhibition as expressed by positive and negative shifts
      in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory
      behaviors, the EGN model is able to mimic functional connectivity dynamics,
      approximate fMRI time series on the basis of initial subset of available data, as
      well as simulate the impact of network lesions and provide evidence of
      compensation mechanisms across networks. Results suggest evolutionary game theory
      on networks as a new potential framework for the understanding of human brain
      network dynamics.

PMID- 29167479
TI  - Femtosecond to picosecond transient effects in WSe 2 observed by pump-probe angle
      resolved photoemission spectroscopy.
AB  - Time-dependent responses of materials to an ultrashort optical pulse carry
      valuable information about the electronic and lattice dynamics; this research
      area has been widely studied on novel two-dimensional materials such as graphene,
      transition metal dichalcogenides (TMDs) and topological insulators (TIs). We
      report herein a time-resolved and angle-resolved photoemission spectroscopy
      (TRARPES) study of WSe2, a layered semiconductor of interest for valley
      electronics. The results for below-gap optical pumping reveal energy-gain and 
      loss Floquet replica valence bands that appear instantaneously in concert with
      the pump pulse. Energy shift, broadening, and complex intensity variation and
      oscillation at twice the phonon frequency for the valence bands are observed at
      time scales ranging from the femtosecond to the picosecond and beyond. The
      underlying physics is rich, including ponderomotive interaction, dressing of the
      electronic states, creation of coherent phonon pairs, and diffusion of charge
      carriers - effects operating at vastly different time domains.

PMID- 29167481
TI  - Influence of experimental parameters on the laser heating of an optical trap.
AB  - In optical tweezers, heating of the sample due to absorption of the laser light
      is a major concern as temperature plays an important role at microscopic scale. A
      popular rule of thumb is to consider that, at the typical wavelength of 1064 nm,
      the focused laser induces a heating rate of B = 1  degrees C/100 mW. We analysed
      this effect under different routine experimental conditions and found a
      remarkable variability in the temperature increase. Importantly, we determined
      that temperature can easily rise by as much as 4  degrees C at a relatively low
      power of 100 mW, for dielectric, non-absorbing particles with certain sets of
      specific, but common, parameters. Heating was determined from measurements of
      light momentum changes under drag forces at different powers, which proved to
      provide precise and robust results in watery buffers. We contrasted the
      experiments with computer simulations and obtained good agreement. These results
      suggest that this remarkable heating could be responsible for changes in the
      sample under study and could lead to serious damage of live specimens. It is
      therefore advisable to determine the temperature increase in each specific
      experiment and avoid the use of a universal rule that could inadvertently lead to
      critical changes in the sample.

PMID- 29167480
TI  - Dynamical Binding Modes Determine Agonistic and Antagonistic Ligand Effects in
      the Prostate-Specific G-Protein Coupled Receptor (PSGR).
AB  - We analysed the ligand-based activation mechanism of the prostate-specific G
      protein coupled receptor (PSGR), which is an olfactory receptor that mediates
      cellular growth in prostate cancer cells. Furthermore, it is an olfactory
      receptor with a known chemically near identic antagonist/agonist pair, alpha- and
      beta-ionone. Using a combined theoretical and experimental approach, we propose
      that this receptor is activated by a ligand-induced rearrangement of a protein
      internal hydrogen bond network. Surprisingly, this rearrangement is not induced
      by interaction of the ligand with the network, but by dynamic van der Waals
      contacts of the ligand with the involved amino acid side chains, altering their
      conformations and intraprotein connectivity. Ligand recognition in this GPCR is
      therefore highly stereo selective, but seemingly lacks any ligand recognition via
      polar contacts. A putative olfactory receptor-based drug design scheme will have
      to take this unique mode of protein/ligand action into account.

PMID- 29167482
TI  - Taxonomy and Identification of the Genus Scolopendra in China Using Integrated
      Methods of External Morphology and Molecular Phylogenetics.
AB  - The centipede Scolopendra has important medicinal value and high toxicity, making
      it to be an interesting subject for evolutionary studies. However, species
      identification in China is difficult because of limited resource exploration and
      lack of recent taxonomic revision. To improve the identification and taxonomy of
      the genus Scolopendra in China, an in-depth investigation was conducted, and an
      integrated method that combined morphological characteristics with molecular data
      was applied. The identification key was revised to show the main difference among
      species. Our results indicated that morphologically-delimited species were
      consistent with the molecular analysis inferred from the COI sequences with
      genetic distances and phylogenetic trees. Additional morphometrics of four
      characteristics provided criteria for shape variation. These results suggested
      that the members of the genus Scolopendra in China could be delineated as 14
      separate species. A new species from Lufeng county, Yunnan province, was proposed
      according to its characteristics, which was named as S. lufengia sp. nov. Our
      results comprehensively ascertained the taxonomic status of Scolopendra species
      in China, explored their phylogenetic relationships, showed a high success in the
      identification of medicinal centipedes.

PMID- 29167483
TI  - Encapsulation of primary dopaminergic neurons in a GDNF-loaded collagen hydrogel
      increases their survival, re-innervation and function after intra-striatal
      transplantation.
AB  - Poor graft survival limits the use of primary dopaminergic neurons for neural
      repair in Parkinson's disease. Injectable hydrogels have the potential to
      significantly improve the outcome of such reparative approaches by providing a
      physical matrix for cell encapsulation which can be further enriched with pro
      survival factors. Therefore, this study sought to determine the survival and
      efficacy of primary dopaminergic grafts after intra-striatal delivery in a glial
      derived neurotrophic factor (GDNF)-loaded collagen hydrogel in a rat model of
      Parkinson's disease. After intra-striatal transplantation into the lesioned
      striatum, the GDNF-enriched collagen hydrogel significantly improved the survival
      of dopaminergic neurons in the graft (5-fold), increased their capacity for
      striatal re-innervation (3-fold), and enhanced their functional efficacy.
      Additional studies suggested that this was due to the hydrogel's ability to
      retain GDNF in the microenvironment of the graft, and to protect the transplanted
      cells from the host immune response. In conclusion, the encapsulation of
      dopaminergic neurons in a GDNF-loaded hydrogel dramatically increased their
      survival and function, providing further evidence of the potential of
      biomaterials for neural transplantation and brain repair in neurodegenerative
      diseases such as Parkinson's disease.

PMID- 29167484
TI  - Possible mechanisms of control of Fusarium wilt of cut chrysanthemum by
      Phanerochaete chrysosporium in continuous cropping fields: A case study.
AB  - Continuous cropping is a universal challenge in agriculture because it has
      adverse physiological effects on plants, resulting in stunting, inferior quality,
      and even massive loss in harvest due to diseases. In this study, Phanerochaete
      chrysosporium was inoculated into the field in which cut chrysanthemum had
      already been continuously cropped for five years to control wilt disease. After
      120 days of cultivation, the addition of P. chrysosporium significantly improved
      the physiological status of plants and changed the bacterial and fungal community
      structure in the soil. The bacterial quantity in the treatment increased by 1.76
      times, but the fungal quantity, especially the quantity of Fusarium oxysporum,
      decreased significantly in comparison with the control. The investigation into
      the mechanisms of control of Fusarium wilt of cut chrysanthemum by P.
      chrysosporium showed that P. chrysosporium in soil can inhibit the growth of F.
      oxysporum and decrease p-hydroxybenzoic acid (HA), which stimulates the
      propagation of F. oxysporum. Based on current evidence, the inhibition by P.
      chrysosporium and change in HA appear to be the main causes of the alleviation of
      wilt disease in the treatment. Other factors, such as nutrients, might also have
      an influence on the wilt disease of cut chrysanthemum.

PMID- 29167485
TI  - Sleep Deprivation Diminishes Attentional Control Effectiveness and Impairs
      Flexible Adaptation to Changing Conditions.
AB  - Insufficient sleep is a global public health problem resulting in catastrophic
      accidents, increased mortality, and hundreds of billions of dollars in lost
      productivity. Yet the effect of sleep deprivation (SD) on decision making and
      performance is often underestimated by fatigued individuals and is only beginning
      to be understood by scientists. The deleterious impact of SD is frequently
      attributed to lapses in vigilant attention, but this account fails to explain
      many SD-related problems, such as loss of situational awareness and
      perseveration. Using a laboratory study protocol, we show that SD individuals can
      maintain information in the focus of attention and anticipate likely correct
      responses, but their use of such a top-down attentional strategy is less
      effective at preventing errors caused by competing responses. Moreover, when the
      task environment requires flexibility, performance under SD suffers dramatically.
      The impairment in flexible shifting of attentional control we observed is
      distinct from lapses in vigilant attention, as corroborated by the specificity of
      the influence of a genetic biomarker, the dopaminergic polymorphism DRD2 C957T.
      Reduced effectiveness of top-down attentional control under SD, especially when
      conditions require flexibility, helps to explain maladaptive performance that is
      not readily explained by lapses in vigilant attention.

PMID- 29167486
TI  - Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid
      Angiopathy.
AB  - Restricted lobar cerebral microbleeds (CMBs) and cortical superficial siderosis
      (CSS) are the characteristic markers of cerebral amyloid angiopathy (CAA).
      However, their effects on clinical features has not been evaluated well. The
      purpose of this study is to investigate the clinical implication of these markers
      in clinical-radiologically diagnosed CAA. A total of 372 patients with possible
      or probable CAA who met the modified Boston criteria were recruited in a memory
      clinic setting. Cortical thickness was measured using surface based methods.
      Presence of restricted multiple lobar CMBs were independently associated with
      cortical thinning across the entire cortical regions while presence of CSS was
      independently associated with cortical thinning primarily in the bilateral
      frontal region. Presence of restricted multiple lobar CMBs was associated with
      impairment in all cognitive domains such as attention, language, visuospatial,
      memory and frontal executive functions while presence of CSS was associated with
      attention and frontal dysfunction. The relationships of restricted multiple lobar
      CMBs or CSS with cognitive impairment were partially mediated by thinning in the
      corresponding cortical regions. Our findings suggested that restricted multiple
      lobar CMBs and CSS affect distinctive clinical features, providing new insights
      into potential mechanisms in CAA.

PMID- 29167487
TI  - Comparative metagenomics of hydrocarbon and methane seeps of the Gulf of Mexico.
AB  - Oil and gas percolate profusely through the sediments of the Gulf of Mexico,
      leading to numerous seeps at the seafloor, where complex microbial, and sometimes
      animal communities flourish. Sediments from three areas (two cold seeps with
      contrasting hydrocarbon composition and a site outside any area of active
      seepage) of the Gulf of Mexico were investigated and compared. Consistent with
      the existence of a seep microbiome, a distinct microbial community was observed
      in seep areas compared to sediment from outside areas of active seepage. The
      microbial community from sediments without any influence from hydrocarbon seepage
      was characterized by Planctomycetes and the metabolic potential was consistent
      with detrital marine snow degradation. By contrast, in seep samples with methane
      as the principal hydrocarbon, methane oxidation by abundant members of ANME-1 was
      likely the predominant process. Seep samples characterized by fluids containing
      both methane and complex hydrocarbons, were characterized by abundant Chloroflexi
      (Anaerolinaceae) and deltaproteobacterial lineages and exhibited potential for
      complex hydrocarbon degradation. These different metabolic capacities suggested
      that microorganisms in cold seeps can potentially rely on other processes beyond
      methane oxidation and that the hydrocarbon composition of the seep fluids may be
      a critical factor structuring the seafloor microbial community composition and
      function.

PMID- 29167488
TI  - Mott transition in chain structure of strained VO2 films revealed by coherent
      phonons.
AB  - The characteristic of strongly correlated materials is the Mott transition
      between metal and insulator (MIT or IMT) in the same crystalline structure,
      indicating the presence of a gap formed by the Coulomb interaction between
      carriers. The physics of the transition needs to be revealed. Using VO2, as a
      model material, we observe the emergence of a metallic chain in the intermediate
      insulating monoclinic structure (M2 phase) of epitaxial strained films, proving
      the Mott transition involving the breakdown of the critical Coulomb interaction.
      It is revealed by measuring the temperature dynamics of coherent optical phonons
      with separated vibrational modes originated from two substructures in M2: one is
      the charge-density-wave, formed by electron-phonon (e-ph) interaction, and the
      other is the equally spaced insulator-chain with electron-electron (e-e)
      correlations.

PMID- 29167489
TI  - T helper cells with specificity for an antigen in cardiomyocytes promote pressure
      overload-induced progression from hypertrophy to heart failure.
AB  - We investigated whether CD4+-T cells with specificity for an antigen in
      cardiomyocytes promote the progression from hypertrophy to heart failure in mice
      with increased pressure load due to transverse aortic constriction (TAC). OT-II
      mice expressing a transgenic T cell receptor (TCR) with specificity for ovalbumin
      (OVA) on CD4+-T cells and cMy-mOVA mice expressing OVA on cardiomyocytes were
      crossed. The resulting cMy-mOVA-OT-II mice did not display signs of spontaneous
      autoimmunity despite the fact that their OVA-specific CD4+-T cells were not
      anergic. After TAC, progression to heart failure was significantly accelerated in
      cMy-mOVA-OT-II compared to cMy-mOVA mice. No OVA-specific antibodies were induced
      in response to TAC in cMy-mOVA-OT-II mice, yet more CD3+ T cells infiltrated
      their myocardium when compared with TAC-operated cMy-mOVA mice. Systemically, the
      proportion of activated CD4+-T cells with a Th1 and Th17 cytokine profile was
      increased in cMy-mOVA-OT-II mice after TAC. Thus, T helper cells with specificity
      for an antigen in cardiomyocytes can directly promote the progression of heart
      failure in response to pressure overload independently of autoantibodies.

PMID- 29167490
TI  - Strongly Coupled Magnetic and Electronic Transitions in Multivalent Strontium
      Cobaltites.
AB  - The topotactic phase transition in SrCoO x (x = 2.5-3.0) makes it possible to
      reversibly transit between the two distinct phases, i.e. the brownmillerite
      SrCoO2.5 that is a room-temperature antiferromagnetic insulator (AFM-I) and the
      perovskite SrCoO3 that is a ferromagnetic metal (FM-M), owing to their multiple
      valence states. For the intermediate x values, the two distinct phases are
      expected to strongly compete with each other. With oxidation of SrCoO2.5,
      however, it has been conjectured that the magnetic transition is decoupled to the
      electronic phase transition, i.e., the AFM-to-FM transition occurs before the
      insulator-to-metal transition (IMT), which is still controversial. Here, we
      bridge the gap between the two-phase transitions by density-functional theory
      calculations combined with optical spectroscopy. We confirm that the IMT actually
      occurs concomitantly with the FM transition near the oxygen content x = 2.75.
      Strong charge-spin coupling drives the concurrent IMT and AFM-to-FM transition,
      which fosters the near room-T magnetic transition characteristic. Ultimately, our
      study demonstrates that SrCoO x is an intriguingly rare candidate for inducing
      coupled magnetic and electronic transition via fast and reversible redox
      reactions.

PMID- 29167491
TI  - Use of cues in virtual reality depends on visual feedback.
AB  - 3D motion perception is of central importance to daily life. However, when tested
      in laboratory settings, sensitivity to 3D motion signals is found to be poor,
      leading to the view that heuristics and prior assumptions are critical for 3D
      motion perception. Here we explore an alternative: sensitivity to 3D motion
      signals is context-dependent and must be learned based on explicit visual
      feedback in novel environments. The need for action-contingent visual feedback is
      well-established in the developmental literature. For example, young kittens that
      are passively moved through an environment, but unable to move through it
      themselves, fail to develop accurate depth perception. We find that these
      principles also obtain in adult human perception. Observers that do not
      experience visual consequences of their actions fail to develop accurate 3D
      motion perception in a virtual reality environment, even after prolonged
      exposure. By contrast, observers that experience the consequences of their
      actions improve performance based on available sensory cues to 3D motion.
      Specifically, we find that observers learn to exploit the small motion parallax
      cues provided by head jitter. Our findings advance understanding of human 3D
      motion processing and form a foundation for future study of perception in virtual
      and natural 3D environments.

PMID- 29167492
TI  - Radioligand binding analysis of alpha 2 adrenoceptors with [11C]yohimbine in
      brain in vivo: Extended Inhibition Plot correction for plasma protein binding.
AB  - We describe a novel method of kinetic analysis of radioligand binding to
      neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat
      brain. The method uses positron emission tomography (PET) of [11C]yohimbine
      binding in brain to quantify the density and affinity of alpha 2 adrenoceptors
      under condition of changing radioligand binding to plasma proteins. We obtained
      dynamic PET recordings from brain of Spraque Dawley rats at baseline, followed by
      pharmacological challenge with unlabeled yohimbine (0.3 mg/kg). The challenge
      with unlabeled ligand failed to diminish radioligand accumulation in brain
      tissue, due to the blocking of radioligand binding to plasma proteins that
      elevated the free fractions of the radioligand in plasma. We devised a method
      that graphically resolved the masking of unlabeled ligand binding by the increase
      of radioligand free fractions in plasma. The Extended Inhibition Plot introduced
      here yielded an estimate of the volume of distribution of non-displaceable ligand
      in brain tissue that increased with the increase of the free fraction of the
      radioligand in plasma. The resulting binding potentials of the radioligand
      declined by 50-60% in the presence of unlabeled ligand. The kinetic unmasking of
      inhibited binding reflected in the increase of the reference volume of
      distribution yielded estimates of receptor saturation consistent with the binding
      of unlabeled ligand.

PMID- 29167494
TI  - Picture Interpretation Test (PIT) 360 degrees : An Innovative Measure of
      Executive Functions.
AB  - The assessment of executive functions poses researchers with several challenges
      related to both the complexity of the construct of executive functions itself
      and/or the methodological difficulties related to its evaluation. The main
      objective of the current study was to evaluate a 360 degrees  version of an
      ecologically valid assessment called the Picture Interpretation Test (PIT).
      Participants included 19 patients with Parkinson's disease (PD) and 19 healthy
      controls. All participants endorsed globally positive experiences of the PIT 360
      degrees . Furthermore, findings indicated that patients with PD took longer to
      correctly interpret the PIT 360 degrees  scene and tended to significantly focus
      on details of the 360 degrees  scene instead of the most informative elements.
      The time needed for a correct interpretation of the presented scene also
      correlated significantly with performance in conventional paper and pencil tests
      of executive functions for patients with PD. Classification analysis indicated
      the potential of the PIT 360 degrees  for distinguishing between patients with PD
      and healthy controls. Overall, these data provide preliminary evidence in support
      of the PIT 360 degrees  for evaluating executive functions.

PMID- 29167493
TI  - Functional aspects of salivary nitric oxide synthase of Rhodnius prolixus
      (Hemiptera, Reduviidae) and nitric oxide trafficking at the vector-host
      interface.
AB  - Rhodnius prolixus expresses nitric oxide synthase (NOS) in the cytosol of the
      salivary gland (SG) cells. The NO produced is stored in the SG lumen bound to NO
      carrier haemeproteins called nitrophorins (NPs). NPs bind tightly to NO in the
      acidic SG lumen, but release NO when the pH becomes high, e.g., at the host skin
      (pH~7.4). NO elicits potent and transient relaxation of vascular smooth muscle.
      Here, we investigated the role of salivary NO in the R. prolixus feeding
      behaviour and the salivary vasodilator activity of the host microcirculation. NOS
      knockdown in R. prolixus changed the SG colour, decreased the number of NO-loaded
      NPs and caused impairment of feeding performance. When salivary gland extracts
      (SGEs) were obtained from NOS- and NPs-knockdown insects and prepared in pH 5.0
      solution and injected (i.v.) into mice via the tail vein, no vasodilation was
      observed, whereas SGEs from control insects caused long-term venodilation in the
      mouse skin. SGs disrupted directly in PBS (pH 7.4) containing BSA produced long
      term vasodilation compared to the controls without BSA due to the possible
      formation of nitroso-albumin, suggesting that host serum albumin extends the NO
      half-life when NO is injected into the host skin by triatomine during their blood
      feeding.

PMID- 29167495
TI  - Changes in cardiac arrest patients' temperature management after the publication
      of 2015 AHA guidelines for resuscitation in China.
AB  - A survey was performed to assess the current management of targeted temperature
      management (TTM) in patients following cardiac arrest (CA) and whether healthcare
      providers will change target temperature after publication of 2015 American Heart
      Association guidelines for resuscitation in China. 52 hospitals were selected
      from whole of China between August to November 2016. All healthcare providers in
      EMs and/or ICUs of selected hospitals participated in the study. 1952 respondents
      fulfilled the survey (86.8%). TTM in CA patients was declared by 14.5% of
      physicians and 6.7% of the nurses. Only 4 of 64 departments, 7.8% of physicians
      and 5.7% of the nurses had implemented TH for CA patients. Since the publication
      of 2015 AHA guidelines, 33.6% of respondents declared no modification of target
      temperature, whereas 51.5% declared a target temperature's change in future
      practice. Respondents were more likely to choose 35~36  degrees C-TTM (54.7%)
      after guidelines publication, as compared to that before guidelines publication
      they preferred 32~34  degrees C-TTM (54.0%). TTM for CA patients was still in the
      early stage in China. Publication of 2015 resuscitation guidelines did have
      impact on choice of target temperature among healthcare providers. They preferred
      35~36  degrees C-TTM after guidelines publication.

PMID- 29167496
TI  - Temporal depolarization of mitochondria during M phase.
AB  - Mitochondrial activity in cells must be tightly controlled in response to changes
      in intracellular circumstances. Despite drastic changes in intracellular
      conditions and mitochondrial morphology, it is not clear how mitochondrial
      activity is controlled during M phase of the cell cycle. Here, we show that
      mitochondrial activity is drastically changed during M phase. Mitochondrial
      membrane potential changed during M phase progression. Mitochondria were
      polarized until metaphase to the same extent as mitochondria in interphase cells,
      but were depolarized at around telophase and cytokinesis. After cytokinesis,
      mitochondrial membrane potential was recovered. In addition, the generation of
      superoxide anions in mitochondria was significantly reduced at metaphase even in
      the presence of antimycin A, an inhibitor of complex III. These results suggest
      that the electron supply to the mitochondrial electron transfer chain is
      suppressed during M phase. This suppression might decrease the reactive oxygen
      species generated by the fragmentation of mitochondria during M phase.

PMID- 29167498
TI  - Micromechanical Resonator Driven by Radiation Pressure Force.
AB  - Radiation pressure exerted by light on any surface is the pressure generated by
      the momentum of impinging photons. The associated force - fundamentally, a
      quantum mechanical aspect of light - is usually too small to be useful, except in
      large-scale problems in astronomy and astrodynamics. In atomic and molecular
      optics, radiation pressure can be used to trap or cool atoms and ions. Use of
      radiation pressure on larger objects such as micromechanical resonators has been
      so far limited to its coupling to an acoustic mode, sideband cooling, or
      levitation of microscopic objects. In this Letter, we demonstrate direct
      actuation of a radio-frequency micromechanical plate-type resonator by the
      radiation pressure force generated by a standard laser diode at room temperature.
      Using two independent methods, the magnitude of the resonator's response to
      forcing by radiation pressure is found to be proportional to the intensity of the
      incident light.

PMID- 29167497
TI  - Development and validation of scFv-conjugated affinity silk protein for specific
      detection of carcinoembryonic antigen.
AB  - The production costs for monoclonal antibodies (MAbs) utilized in medical
      diagnostic kits are inevitably high because the MAbs are mostly obtained from
      hybridoma cell culture. Here, we report the development and validation of a novel
      affinity silk protein produced by transgenic silkworm technology as a possible
      alternative diagnostic tool for cancers. We generated a transgenic silkworm
      expressing a cDNA construct containing fibroin L-chain fused to a single-chain
      variable fragment (scFv) derived from a MAb against carcinoembryonic antigen
      (CEA). The transgenic cocoons were dissolved in aqueous lithium bromide solution,
      applied to 96-well plates, and analysed by enzyme-linked immunosorbent assay. The
      scFv-conjugated affinity silk protein specifically recognized CEA as well as the
      parental MAb. The binding activity was retained after several months of storage
      in coated plates or concentrated solution. Thus, the scFv-conjugated affinity
      silk protein provides a potentially useful alternative to conventional MAbs in
      medical diagnostic kits.

PMID- 29167499
TI  - A Novel Multiplex HRM Assay to Detect Clopidogrel Resistance.
AB  - Clopidogrel is an antiplatelet medicine used to prevent blood clots in patients
      who have had a heart attack, stroke, or other symptoms. Variability in the
      clinical response to clopidogrel treatment has been attributed to genetic
      factors. In particular, five SNPs of rs4244285, rs4986893, rs12248560, rs662 and
      rs1045642 have been associated with resistance to clopidogrel therapy in Chinese
      population. This work involves the development of a multiplex high-resolution
      melting (HRM) assay to genotype all five of these loci in 2 tubes. Amplicons
      corresponding to distinct SNPs in a common tube were designed with the aid of
      uMelt prediction software to have different melting temperatures Tm by addition
      of a GC-rich tail to the 5' end of the certain primers. Two kinds of commercial
      methods, Digital Fluorescence Molecular Hybridization (DFMH) and Sanger
      sequencing, were used as a control. Three hundred sixteen DFMH pretested samples
      from consecutive acute coronary syndrome patients were used for a blinded study
      of multiplex HRM. The sensitivity of HRM was 100% and the specificity was 99.93%
      reflecting detection of variants other than the known resistance SNPs. Multiplex
      HRM is an effective closed-tube, highly accurate, fast, and inexpensive method
      for genotyping the 5 clopidogrel resistance associated SNPs.

PMID- 29167500
TI  - Insights into the species-specific metabolic engineering of glucosinolates in
      radish (Raphanus sativus L.) based on comparative genomic analysis.
AB  - Glucosinolates (GSLs) and their hydrolysis products present in Brassicales play
      important roles in plants against herbivores and pathogens as well as in the
      protection of human health. To elucidate the molecular mechanisms underlying the
      formation of species-specific GSLs and their hydrolysed products in Raphanus
      sativus L., we performed a comparative genomics analysis between R. sativus and
      Arabidopsis thaliana. In total, 144 GSL metabolism genes were identified, and
      most of these GSL genes have expanded through whole-genome and tandem duplication
      in R. sativus. Crucially, the differential expression of FMOGS-OX2 in the root
      and silique correlates with the differential distribution of major aliphatic GSL
      components in these organs. Moreover, MYB118 expression specifically in the
      silique suggests that aliphatic GSL accumulation occurs predominantly in seeds.
      Furthermore, the absence of the expression of a putative non-functional
      epithiospecifier (ESP) gene in any tissue and the nitrile-specifier (NSP) gene in
      roots facilitates the accumulation of distinctive beneficial isothiocyanates in
      R. sativus. Elucidating the evolution of the GSL metabolic pathway in R. sativus
      is important for fully understanding GSL metabolic engineering and the precise
      genetic improvement of GSL components and their catabolites in R. sativus and
      other Brassicaceae crops.

PMID- 29167501
TI  - Dengue fatal cases present virus-specific HMGB1 response in peripheral organs.
AB  - Dengue is an important infectious disease that presents high incidence and yields
      a relevant number of fatal cases (about 20,000) every year worldwide. Despite its
      epidemiological relevance, there are many knowledge gaps concerning dengue
      pathogenesis, especially with regards to the circumstances that drive a mild
      clinical course to a severe disease. In this work, we investigated the
      participation of high mobility group box 1 (HMGB1), an important modulator of
      inflammation, in dengue fatal cases. Histopathological and ultrastructural
      analyses revealed that liver, lung and heart post-mortem samples were marked by
      tissue abnormalities, such as necrosis and apoptotic cell death. These
      observations go in line with an HMGB1-mediated response and raised concerns
      regarding the participation of this cytokine in promoting/perpetuating
      inflammation in severe dengue. Further experiments of immunohistochemistry (IHC)
      showed increased expression of cytoplasmic HMGB1 in dengue-extracted tissues when
      compared to non-dengue controls. Co-staining of DENV RNA and HMGB1 in the host
      cell cytoplasm, as found by in situ hybridization and IHC, confirmed the virus
      specific induction of the HMGB1-mediated response in these peripheral tissues.
      This report brings the first in-situ evidence of the participation of HMGB1 in
      severe dengue and highlights novel considerations in the development of dengue
      immunopathogenesis.

PMID- 29167502
TI  - Effect of maternal glycemia and weight status on offspring birth measures and BMI
      z among Chinese population in the first year.
AB  - To investigate the effects of maternal fasting plasma glucose (FPG) and pre
      pregnancy weight status (PPWS) on offspring birth measures and body mass index z
      score (BMI-z) in the first year, we conducted a prospective study of 1,096 mother
      infant dyads in Guangdong, China, 2014-2015. Multivariate logistic regression was
      used to test independent/interaction associations of maternal FPG and PPWS with
      macrosomia/large for gestational age (LGA). Association of PPWS and FPG with
      offspring BMI-z in the first year was assessed by the linear mixed effects
      models. For each 1-mmol/L increase in FPG, the risk of macrosomia and LGA was
      elevated by 2.74 and 2.01 (95% CI: 1.85, 7.60 and 1.54, 5.88), respectively. No
      main effect of PPWS or interaction association of FPG and PPWS on macrosomia/LGA
      was observed (P > 0.05). A relation between maternal FPG and PPWS was detected (P
      < 0.05). Infants of Q5 FPG mothers, those who were born to OWO mothers, had a
      0.35 increase in the BMI-z (95% CI: 0.16, 0.55) compared with infants of NW
      mothers. In conclusion, maternal FPG is positively associated with
      macrosomia/LGA. Maternal PPWS and FPG considerably interacted for the association
      with the risk of offspring high BMI-z in the first year.

PMID- 29167503
TI  - Structural analyses of adenylate kinases from Antarctic and tropical fishes for
      understanding cold adaptation of enzymes.
AB  - Psychrophiles are extremophilic organisms capable of thriving in cold
      environments. Proteins from these cold-adapted organisms can remain
      physiologically functional at low temperatures, but are structurally unstable
      even at moderate temperatures. Here, we report the crystal structure of adenylate
      kinase (AK) from the Antarctic fish Notothenia coriiceps, and identify the
      structural basis of cold adaptation by comparison with homologues from tropical
      fishes including Danio rerio. The structure of N. coriiceps AK (AKNc) revealed
      suboptimal hydrophobic packing around three Val residues in its central CORE
      domain, which are replaced with Ile residues in D. rerio AK (AKDr). The Val-to
      Ile mutations that improve hydrophobic CORE packing in AKNc increased stability
      at high temperatures but decreased activity at low temperatures, suggesting that
      the suboptimal hydrophobic CORE packing is important for cold adaptation. Such
      linkage between stability and activity was also observed in AKDr. Ile-to-Val
      mutations that destabilized the tropical AK resulted in increased activity at low
      temperatures. Our results provide the structural basis of cold adaptation of a
      psychrophilic enzyme from a multicellular, eukaryotic organism, and highlight the
      similarities and differences in the structural adjustment of vertebrate and
      bacterial psychrophilic AKs during cold adaptation.

PMID- 29167504
TI  - Tunable plasmonic substrates with ultrahigh Q-factor resonances.
AB  - Precisely tailored plasmonic substrates can provide a platform for a variety of
      enhanced plasmonic applications in sensing and imaging. Despite the significant
      advances made in plasmonics, most plasmonic devices suffer critically from
      intrinsic absorption losses at optical frequencies, fatally restricting their
      efficiency. Here, we describe and engineer plasmonic substrates based on metal
      insulator-metal (MIM) plasmon resonances with ultra-sharp optical transmission
      responses. Due to their sharp transmission spectrum, the proposed substrates can
      be utilized for high quality (Q)-factor multi-functional plasmonic applications.
      Analytical and numerical methods are exploited to investigate the optical
      properties of the substrates. The optical response of the substrate can be tuned
      by adjusting the periodicity of the nanograting patterned on the substrate.
      Fabricated substrates present Q-factors as high as ~40 and refractive index
      sensing of the surrounding medium as high as 1245 nm/RIU. Our results indicate
      that by engineering the substrate geometry, the dielectric thickness and incident
      angle, the radiation losses can be greatly diminished, thus enabling the design
      of plasmonic substrates with large Q factor and strong sensitivity to the
      environment.

PMID- 29167505
TI  - Dissecting the Re-Os molybdenite geochronometer.
AB  - Rhenium and osmium isotopes have been used for decades to date the formation of
      molybdenite (MoS2), a common mineral in ore deposits and the world's main source
      of molybdenum and rhenium. Understanding the distribution of parent 187Re and
      radiogenic daughter 187Os isotopes in molybdenite is critical in interpreting
      isotopic measurements because it can compromise the accurate determination and
      interpretation of mineralization ages. In order to resolve the controls on the
      distribution of these elements, chemical and isotope mapping of MoS2 grains from
      representative porphyry copper-molybdenum deposits were performed using electron
      microprobe and nano-scale secondary ion mass spectrometry. Our results show a
      heterogeneous distribution of 185,187Re and 192Os isotopes in MoS2, and that both
      187Re and 187Os isotopes are not decoupled as previously thought. We conclude
      that Re and Os are structurally bound or present as nanoparticles in or next to
      molybdenite grains, recording a complex formation history and hindering the use
      of microbeam techniques for Re-Os molybdenite dating. Our study opens new avenues
      to explore the effects of isotope nuggeting in geochronometers.

PMID- 29167506
TI  - Creation and Annihilation of Skyrmions in the Frustrated Magnets with Competing
      Exchange Interactions.
AB  - In triangular-lattice magnets, the coexistence of third-neighbor
      antiferromagnetic and nearest-neighbor ferromagnetic exchange interactions can
      induce rich magnetic phases including noncoplanar skyrmion crystals. Based on
      Monte Carlo simulation, we studied the dependence of magnetic phase transition on
      exchange interaction strength. Under the consideration of uniaxial anisotropy and
      magnetic field both perpendicular to the film plane, a large antiferromagnetic
      exchange interaction induces a high frustration. When the value of
      antiferromagnetic exchange interaction is one and a half times larger than the
      ferromagnetic one, a magnetic phase composed of canting spin stripes, never
      observed in the chiral magnets, forms. Interestingly, different canting spin
      stripes along three 120 degree propagation directions may coexist randomly in a
      magnetic phase, attesting that the canting spin stripes are three-fold degenerate
      states akin to helices and the multiple state of canting spin stripes is a
      circular configuration with zero skyrmion charge number. Moreover, skyrmions and
      antiskyrmions can be observed simultaneously in the configuration at the low
      temperature nearly close to 0 K, and their configuration and diameter properties
      are discussed. Finally, the mechanisms of skyrmion creation and annihilation are
      properly interpreted by comparing exchange and Zeeman energy terms.

PMID- 29167508
TI  - Coral individuality - confluence of change physical splitting and developmental
      ability of embryos.
AB  - Previous studies have suggested that blastomeres from the 2-, 4-, or 8-cell stage
      of corals have the ability to develop into normal primary polyps. However, it is
      still not known which developmental stage's blastomere produces which juvenile.
      In this study, we demonstrated that only the blastomeres with animal hemispheres
      have the capacity to develop into normal primary polyps. Individuality was
      evaluated using blastomeres isolated from the corals Acropora digitifera, A.
      intermedia, Dipsastraea lizardensis, and Favites chinensis. On commencement of
      embryo cleavage, the animal pole was marked using Neutral red staining, and at
      the 2-, 4-, and 8-cell stages, embryos were divided into individual blastomeres
      using glass needles. We found that the survival rate and percentage metamorphosis
      were higher in the larger-sized blastomeres with animal hemispheres. The vegetal
      hemisphere alone is incapable of developing into a normal primary polyp; however,
      a ball-shaped embryo with incomplete mesenteries and no pharynx developed in some
      cases. These results indicate that the animal hemisphere is needed for corals to
      develop into normal primary polyps, and that the individuality of corals is
      possibly determined by a combination of the chance physical splitting of embryos
      by waves and their innate developmental ability.

PMID- 29167507
TI  - Characterization of the early molecular changes in the glomeruli of Cd151 -/-
      mice highlights induction of mindin and MMP-10.
AB  - In humans and FVB/N mice, loss of functional tetraspanin CD151 is associated with
      glomerular disease characterised by early onset proteinuria and ultrastructural
      thickening and splitting of the glomerular basement membrane (GBM). To gain
      insight into the molecular mechanisms associated with disease development, we
      characterised the glomerular gene expression profile at an early stage of disease
      progression in FVB/N Cd151 -/- mice compared to Cd151 +/+ controls. This study
      identified 72 up-regulated and 183 down-regulated genes in FVB/N Cd151 -/-
      compared to Cd151 +/+ glomeruli (p < 0.05). Further analysis highlighted
      induction of the matrix metalloprotease MMP-10 and the extracellular matrix
      protein mindin (encoded by Spon2) in the diseased FVB/N Cd151 -/- GBM that did
      not occur in the C57BL/6 diseased-resistant strain. Interestingly, mindin was
      also detected in urinary samples of FVB/N Cd151 -/- mice, underlining its
      potential value as a biomarker for glomerular diseases associated with GBM
      alterations. Gene set enrichment and pathway analysis of the microarray dataset
      showed enrichment in axon guidance and actin cytoskeleton signalling pathways as
      well as activation of inflammatory pathways. Given the known function of mindin,
      its early expression in the diseased GBM could represent a trigger of both
      further podocyte cytoskeletal changes and inflammation, thereby playing a key
      role in the mechanisms of disease progression.

PMID- 29167509
TI  - Cartilage intermediate layer protein 1 (CILP1): A novel mediator of cardiac
      extracellular matrix remodelling.
AB  - Heart failure is accompanied by extracellular matrix (ECM) remodelling, often
      leading to cardiac fibrosis. In the present study we explored the significance of
      cartilage intermediate layer protein 1 (CILP1) as a novel mediator of cardiac ECM
      remodelling. Whole genome transcriptional analysis of human cardiac tissue
      samples revealed a strong association of CILP1 with many structural (e.g. COL1A2
      r2 = 0.83) and non-structural (e.g. TGFB3 r2 = 0.75) ECM proteins. Gene
      enrichment analysis further underscored the involvement of CILP1 in human cardiac
      ECM remodelling and TGFbeta signalling. Myocardial CILP1 protein levels were
      significantly elevated in human infarct tissue and in aortic valve stenosis
      patients. CILP1 mRNA levels markedly increased in mouse heart after myocardial
      infarction, transverse aortic constriction, and angiotensin II treatment. Cardiac
      fibroblasts were found to be the primary source of cardiac CILP1 expression.
      Recombinant CILP1 inhibited TGFbeta-induced alphaSMA gene and protein expression
      in cardiac fibroblasts. In addition, CILP1 overexpression in HEK293 cells
      strongly (5-fold p < 0.05) inhibited TGFbeta signalling activity. In conclusion,
      our study identifies CILP1 as a new cardiac matricellular protein interfering
      with pro-fibrotic TGFbeta signalling, and as a novel sensitive marker for cardiac
      fibrosis.

PMID- 29167510
TI  - Connection adaption for control of networked mobile chaotic agents.
AB  - In this paper, we propose a strategy for the control of mobile chaotic
      oscillators by adaptively rewiring connections between nearby agents with local
      information. In contrast to the dominant adaptive control schemes where coupling
      strength is adjusted continuously according to the states of the oscillators, our
      method does not request adaption of coupling strength. As the resulting
      interaction structure generated by this proposed strategy is strongly related to
      unidirectional chains, by investigating synchronization property of
      unidirectional chains, we reveal that there exists a certain coupling range in
      which the agents could be controlled regardless of the length of the chain. This
      feature enables the adaptive strategy to control the mobile oscillators
      regardless of their moving speed. Compared with existing adaptive control
      strategies for networked mobile agents, our proposed strategy is simpler for
      implementation where the resulting interaction networks are kept unweighted at
      all time.

PMID- 29167511
TI  - Transcription factor NF-kappaB is modulated by symbiotic status in a sea anemone
      model of cnidarian bleaching.
AB  - Transcription factor NF-kappaB plays a central role in immunity from fruit flies
      to humans, and NF-kappaB activity is altered in many human diseases. To
      investigate a role for NF-kappaB in immunity and disease on a broader
      evolutionary scale we have characterized NF-kappaB in a sea anemone (Exaiptasia
      pallida; called Aiptasia herein) model for cnidarian symbiosis and dysbiosis
      (i.e., "bleaching"). We show that the DNA-binding site specificity of Aiptasia NF
      kappaB is similar to NF-kappaB proteins from a broad expanse of organisms.
      Analyses of NF-kappaB and IkappaB kinase proteins from Aiptasia suggest that non
      canonical NF-kappaB processing is an evolutionarily ancient pathway, which can be
      reconstituted in human cells. In Aiptasia, NF-kappaB protein levels, DNA-binding
      activity, and tissue expression increase when loss of the algal symbiont
      Symbiodinium is induced by heat or chemical treatment. Kinetic analysis of NF
      kappaB levels following loss of symbiosis show that NF-kappaB levels increase
      only after Symbiodinium is cleared. Moreover, introduction of Symbiodinium into
      naive Aiptasia larvae results in a decrease in NF-kappaB expression. Our results
      suggest that Symbiodinium suppresses NF-kappaB in order to enable establishment
      of symbiosis in Aiptasia. These results are the first to demonstrate a link
      between changes in the conserved immune regulatory protein NF-kappaB and
      cnidarian symbiotic status.

PMID- 29167512
TI  - Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair
      blood-brain barrier function in an in vitro model of CNS tuberculosis.
AB  - Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity
      associated with severe inflammation. The blood-brain barrier (BBB) protects the
      brain from inflammation but the mechanisms causing BBB damage in CNS TB are
      uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes
      breakdown of type IV collagen and decreases tight junction protein (TJP)
      expression in a co-culture model of the BBB. This increases permeability, surface
      expression of endothelial adhesion molecules and leukocyte transmigration. TJP
      breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)
      9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription
      factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb
      stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a
      glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh
      delivery to brain endothelial cells. Activation of the hedgehog pathway by
      addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing
      MMP-9 activity, decreased permeability and increased TJP expression in the Mtb
      stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of
      the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity
      which suggests that these pathways are potential novel targets for host directed
      therapy in CNS TB.

PMID- 29167513
TI  - Band gap engineering of In(Ga)N/GaN short period superlattices.
AB  - Discussion of band gap behavior based on first principles calculations of the
      electronic band structures for several InN/GaN superlattices (SLs) (free-standing
      and pseudomorphic) grown along different directions (polar and nonpolar) is
      presented. Taking into account the dependence on internal strain and lattice
      geometry mainly two factors influence the dependence of the band gap, E g on the
      layer thickness: the internal electric field and the hyb wells) is more
      important. We also consider mIn ridization of well and barrier wave functions. We
      illustrate their influence on the band gap engineering by calculating the
      strength of built-in electric field and the oscillator strength. It appears that
      there are two interesting ranges of layer thicknesses. In one the influence of
      the electric field on the gaps is dominant (wider wells), whereas in the other
      the wave function hybridization (narrow wells) is more important. We also
      consider mIn 0.33 Ga 0.67 N/nGaN SLs, which seem to be easier to fabricate than
      high In content quantum wells. The calculated band gaps are compared with recent
      experimental data. It is shown that for In(Ga)N/GaN superlattices it is possible
      to exceed by far the range of band gap values, which can be realized in ternary
      InGaN alloys.

PMID- 29167514
TI  - Common origin of the gelsolin gene variant in 62 Finnish AGel amyloidosis
      families.
AB  - Finnish gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominantly
      inherited systemic disorder with ophthalmologic, neurologic and dermatologic
      symptoms. Only the gelsolin (GSN) c.640G>A variant has been found in the Finnish
      patients thus far. The purpose of this study was to examine whether the Finnish
      patients have a common ancestor or whether multiple mutation events have occurred
      at c.640G, which is a known mutational hot spot. A total of 79 Finnish AGel
      amyloidosis families including 707 patients were first discovered by means of
      patient interviews, genealogic studies and civil and parish registers. From each
      family 1-2 index patients were chosen. Blood samples were available from 71 index
      patients representing 64 families. After quality control, SNP array genotype data
      were available from 68 patients from 62 nuclear families. All the index patients
      had the same c.640G>A variant (rs121909715). Genotyping was performed using the
      Illumina CoreExome SNP array. The homozygosity haplotype method was used to
      analyse shared haplotypes. Haplotype analysis identified a shared haplotype,
      common to all studied patients. This shared haplotype included 17 markers and was
      361 kb in length (GRCh37 coordinates 9:124003326-124364349) and this level of
      haplotype sharing was found to occur highly unlikely by chance. This GSN
      haplotype ranked as the largest shared haplotype in the 68 patients in a genome
      wide analysis of haplotype block lengths. These results provide strong evidence
      that although there is a known mutational hot spot at GSN c.640G, all of the
      studied 62 Finnish AGel amyloidosis families are genetically linked to a common
      ancestor.

PMID- 29167515
TI  - Symmetry breaking, Josephson oscillation and self-trapping in a self-bound three
      dimensional quantum ball.
AB  - We study spontaneous symmetry breaking (SSB), Josephson oscillation, and self
      trapping in a stable, mobile, three-dimensional matter-wave spherical quantum
      ball self-bound by attractive two-body and repulsive three-body interactions. The
      SSB is realized by a parity-symmetric (a) one-dimensional (1D) double-well
      potential or (b) a 1D Gaussian potential, both along the z axis and no potential
      along the x and y axes. In the presence of each of these potentials, the
      symmetric ground state dynamically evolves into a doubly-degenerate SSB ground
      state. If the SSB ground state in the double well, predominantly located in the
      first well (z > 0), is given a small displacement, the quantum ball oscillates
      with a self-trapping in the first well. For a medium displacement one encounters
      an asymmetric Josephson oscillation. The asymmetric oscillation is a consequence
      of SSB. The study is performed by a variational and a numerical solution of a non
      linear mean-field model with 1D parity-symmetric perturbations.

PMID- 29167516
TI  - Nanoparticle core stability and surface functionalization drive the mTOR
      signaling pathway in hepatocellular cell lines.
AB  - Specifically designed and functionalized nanoparticles hold great promise for
      biomedical applications. Yet, the applicability of nanoparticles is critically
      predetermined by their surface functionalization and biodegradability. Here we
      demonstrate that amino-functionalized polystyrene nanoparticles (PS-NH2), but not
      amino- or hydroxyl-functionalized silica particles, trigger cell death in
      hepatocellular carcinoma Huh7 cells. Importantly, biodegradability of
      nanoparticles plays a crucial role in regulation of essential cellular processes.
      Thus, biodegradable silica nanoparticles having the same shape, size and surface
      functionalization showed opposite cellular effects in comparison with similar
      polystyrene nanoparticles. At the molecular level, PS-NH2 obstruct and amino
      functionalized silica nanoparticles (Si-NH2) activate the mTOR signalling in Huh7
      and HepG2 cells. PS-NH2 induced time-dependent lysosomal destabilization
      associated with damage of the mitochondrial membrane. Solely in PS-NH2-treated
      cells, permeabilization of lysosomes preceded cell death. Contrary, Si-NH2
      nanoparticles enhanced proliferation of HuH7 and HepG2 cells. Our findings
      demonstrate complex cellular responses to functionalized nanoparticles and
      suggest that nanoparticles can be used to control activation of mTOR signaling
      with subsequent influence on proliferation and viability of HuH7 cells. The data
      provide fundamental knowledge which could help in developing safe and efficient
      nano-therapeutics.

PMID- 29167517
TI  - The spatiotemporal system dynamics of acquired resistance in an engineered
      microecology.
AB  - Great strides have been made in the understanding of complex networks; however,
      our understanding of natural microecologies is limited. Modelling of complex
      natural ecological systems has allowed for new findings, but these models
      typically ignore the constant evolution of species. Due to the complexity of
      natural systems, unanticipated interactions may lead to erroneous conclusions
      concerning the role of specific molecular components. To address this, we use a
      synthetic system to understand the spatiotemporal dynamics of growth and to study
      acquired resistance in vivo. Our system differs from earlier synthetic systems in
      that it focuses on the evolution of a microecology from a killer-prey
      relationship to coexistence using two different non-motile Escherichia coli
      strains. Using empirical data, we developed the first ecological model
      emphasising the concept of the constant evolution of species, where the survival
      of the prey species is dependent on location (distance from the killer) or the
      evolution of resistance. Our simple model, when expanded to complex
      microecological association studies under varied spatial and nutrient backgrounds
      may help to understand the complex relationships between multiple species in
      intricate natural ecological networks. This type of microecological study has
      become increasingly important, especially with the emergence of antibiotic
      resistant pathogens.

PMID- 29167519
TI  - Publisher Correction: Seismic evidence for a possible deep crustal hot zone
      beneath Southwest Washington.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has beenfixed in the paper.

PMID- 29167518
TI  - Encoding of menstrual pain experience with theta oscillations in women with
      primary dysmenorrhea.
AB  - Theta oscillation (4-7 Hz) is well documented for its association with neural
      processes of memory. Pronounced increase of theta activity is commonly observed
      in patients with chronic neurogenic pain. However, its association with encoding
      of pain experience in patients with chronic pain is still unclear. The goal of
      the present study is to investigate the theta encoding of sensory and emotional
      information of long-term menstrual pain in women with primary dysmenorrhea (PDM).
      Forty-six young women with PDM and 46 age-matched control subjects underwent
      resting-state magnetoencephalography study during menstrual and periovulatory
      phases. Our results revealed increased theta activity in brain regions of pain
      processing in women with PDM, including the right parahippocampal gyrus, right
      posterior insula, and left anterior/middle cingulate gyrus during the menstrual
      phase and the left anterior insula and the left middle/inferior temporal gyrus
      during the periovulatory phase. The correlations between theta activity and the
      psychological measures pertaining to pain experience (depression, state anxiety,
      and pain rating index) implicate the role of theta oscillations in emotional and
      sensory processing of pain. The present study provides evidence for the role of
      theta oscillations in encoding the immediate and sustained effects of pain
      experience in young women with PDM.

PMID- 29167520
TI  - High corrosion resistance and weak corrosion anisotropy of an as-rolled Mg-3Al
      1Zn (in wt.%) alloy with strong crystallographic texture.
AB  - Combining with electrochemical corrosion measurements, immersion and hydrogen
      evolution testing performed in 0.9 wt.% NaCl solution at 37  degrees C, the
      corrosion resistance of an as-rolled Mg-3%Al-1%Zn alloy before and after a 3%
      compressive strain along the rolling direction was investigated. Results revealed
      that the corrosion behavior of differently oriented surfaces of the as-rolled
      samples with a strong basal texture was obviously different. Among them, the
      corrosion rate of sample surface with the orientation parallel to the normal
      direction (ND) of the plate was the fastest, the corrosion rate of sample surface
      with the orientation parallel to the rolling direction (RD) of the plate took the
      second place and the corrosion rate of sample surface with the orientation
      parallel to the transverse direction (TD) was the slowest. After being pre
      strained, the activation of a high density of {10-12} twins could remarkably
      reduce the corrosion rate of surrounding alpha-Mg matrix and simultaneously
      weaken the corrosion anisotropy between differently oriented samples. The main
      reason was that similar to grain boundaries, twin boundaries acted as physical
      barriers to the corrosion attack. Moreover, the activated twins increased the
      protectiveness of surface films and then suppressed the micro corrosion couples
      occurred in twinned grains.

PMID- 29167521
TI  - DNA methylation in silkworm genome may provide insights into epigenetic
      regulation of response to Bombyx mori cypovirus infection.
AB  - DNA methylation is an important epigenetic modification that regulates a wide
      range of biological processes including immune response. However, information on
      the epigenetics-mediated immune mechanisms in insects is limited. Therefore, in
      this study, we examined transcriptomes and DNA methylomes in the fat body and
      midgut tissues of silkworm, Bombyx mori with or without B. mori cytoplasmic
      polyhedrosis virus (BmCPV) infection. The transcriptional profile and the genomic
      DNA methylation patterns in the midgut and fat body were tissue-specific and
      dynamically altered after BmCPV challenge. KEGG pathway analysis revealed that
      differentially methylated genes (DMGs) could be involved in pathways of RNA
      transport, RNA degradation, nucleotide excision repair, DNA replication, etc. 27
      genes were shown to have both differential expression and differential
      methylation in the midgut and fat body of infected larvae, respectively,
      indicating that the BmCPV infection-induced expression changes of these genes
      could be mediated by variations in DNA methylation. BS-PCR validated the
      hypomethylation of G2/M phase-specific E3 ubiquitin-protein ligase-like gene in
      the BmCPV infected midgut. These results demonstrated that epigenetic regulation
      may play roles in host-virus interaction in silkworm and would be potential value
      for further studies on mechanism of BmCPV epithelial-specific infection and
      epigenetic regulation in the silkworm.

PMID- 29167522
TI  - Isolation and functional identification of three cuticle protein genes during
      metamorphosis of the beet armyworm, Spodoptera exigua.
AB  - The beet armyworm, Spodoptera exigua (Hubner), is one of the major crop pests and
      is a target for current pest control approaches using insecticides. In this study
      three cuticular protein genes CPG316, CPG860 and CPG4855 have been cloned from 0
      h pupal integument of S. exigua through race PCR Strategy. The deduced amino acid
      sequences were found to contain the RR-2 consensus region of other insect
      cuticular proteins and construct phylogenetic trees for each protein. Using
      quantitative RT-PCR, the developmental expression of the three genes through
      several larval and the early pupal stages was studied. All three genes contribute
      to the endocuticle although CPG316 may have a different role from the other two
      genes. All three newly isolated genes were analyzed and their functions were
      determined by using direct injection of the dsRNA into early 5th instar larvae.
      All genes are expressed in the larvae and early pupae but in different patterns.
      Furthermore, phenotypic results show that these genes have differing effects on
      the development of cuticle, its flexibility and a big role in metamorphosis in
      both larval and pupal stages.

PMID- 29167523
TI  - Author Correction: Genetic polymorphisms of lncRNA-p53 regulatory network genes
      are associated with concurrent chemoradiotherapy toxicities and efficacy in
      nasopharyngeal carcinoma patients.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29167524
TI  - Neuromodulation: On the alert.

PMID- 29167526
TI  - Phospholipase A2-Responsive Phosphate Micelle-Loaded UCNPs for Bioimaging of
      Prostate Cancer Cells.
AB  - We report the effective synthesis of biocompatible upconversion nanoparticles
      (UCNP)-loaded phosphate micelles and successful delivery of UCNPs to prostate
      cancer cells via secreted phospholipase A2 (sPLA-2) enzyme cleavage of the loaded
      micelles for the first time. The activity of the (sPLA-2) enzyme toward the
      synthesized micelles was investigated and confirmed by LC-MS. TEM results showed
      that the micelles have a size distribution of 80 to 150 nm, whereas UCNP-loaded
      micelles range from 200 to 350 nm, indicating the successful loading of UCNPs.
      The selective release of UCNPs to prostate cancer cells rather than other cells,
      specifically cervical cancer cells, was observed and confirmed by a range of
      bioimaging studies. Moreover, cytotoxicity assays confirmed the biocompatibility
      of the UCNP-loaded micelles.

PMID- 29167527
TI  - The effects of diets enriched in omega-3 polyunsaturated fatty acids on systemic
      vaccinia virus infection.
AB  - Omega-3 polyunsaturated fatty acids (PUFA, n-3 fatty acids), the key components
      of fish and flaxseed oils, are increasingly consumed by the public because of
      their potential health benefits and are available by prescription for
      hypertriglyceridemia. However, numerous studies have shown that these compounds
      are immunoregulatory and immunosuppressive and thus may increase susceptibility
      to infection. In this study, we tested the effects of the amount of fat and the
      types of fatty acid in the diet on infection by vaccinia virus, an acute
      infection that begins in the respiratory tract and spreads by viremia to internal
      organs. Male C57Bl6 mice (~5 week old) were fed for 3 weeks prior to infection
      and continuing during infection and recovery one of the following: 1) a normal
      low fat (13% kcal) diet, 2) a low fat diet containing n-3 PUFAs, 3) a high fat
      (41% kcal) diet rich in n-3 PUFAs, 4) a high fat n-6 PUFA diet, or 5) a high fat
      monounsaturated diet. We found no statistically significant differences in the
      susceptibility of mice to viral infection, morbidity, viral organ titers,
      recovery time, or mortality with these diets, indicating that, over this
      approximately 6-week time period, dietary fats did not substantially affect
      responses to poxviral infection.

PMID- 29167525
TI  - Lineage divergence of activity-driven transcription and evolution of cognitive
      ability.
AB  - Excitation-transcription coupling shapes network formation during brain
      development and controls neuronal survival, synaptic function and cognitive
      skills in the adult. New studies have uncovered differences in the
      transcriptional responses to synaptic activity between humans and mice. These
      differences are caused both by the emergence of lineage-specific activity
      regulated genes and by the acquisition of signal-responsive DNA elements in gene
      regulatory regions that determine whether a gene can be transcriptionally induced
      by synaptic activity or alter the extent of its inducibility. Such evolutionary
      divergence may have contributed to lineage-related advancements in cognitive
      abilities.

PMID- 29167528
TI  - Mercury evasion from a boreal peatland shortens the timeline for recovery from
      legacy pollution.
AB  - Peatlands are a major source of methylmercury that contaminates downstream
      aquatic food webs. The large store of mercury (Hg) in peatlands could be a source
      of Hg for over a century even if deposition is dramatically reduced. However, the
      reliability of Hg mass balances can be questioned due to missing long-term land
      atmosphere flux measurements. We used a novel micrometeorological system for
      continuous measurement of Hg peatland-atmosphere exchange to derive the first
      annual Hg budget for a peatland. The evasion of Hg (9.4 ug m-2 yr-1) over the
      course of a year was seven times greater than stream Hg export, and over two
      times greater than wet bulk deposition to the boreal peatland. Measurements of
      dissolved gaseous Hg in the peat pore water also indicate Hg evasion. The net
      efflux may result from recent declines in atmospheric Hg concentrations that have
      turned the peatland from a net sink into a source of atmospheric Hg. This net Hg
      loss suggests that open boreal peatlands and downstream ecosystems can recover
      more rapidly from past atmospheric Hg deposition than previously assumed. This
      has important implications for future levels of methylmercury in boreal
      freshwater fish and the estimation of historical Hg accumulation rates from peat
      profiles.

PMID- 29167529
TI  - Liver-specific deletion of RORalpha aggravates diet-induced nonalcoholic
      steatohepatitis by inducing mitochondrial dysfunction.
AB  - Mitochondrial dysfunction may play a key role in the progression of steatosis to
      nonalcoholic steatohepatitis (NASH); however, the molecular mechanism that
      controls the structure and function of mitochondria in NASH is not clearly
      understood. Here, we demonstrated that RORalpha is a regulator of expression of
      Bnip3 and PGC-1alpha, and thereby enhances mitochondrial quality. First, we
      observed that liver-specific RORalpha knockout mice (RORalpha-LKO) were more
      susceptible to high-fat diet-induced NASH compared with control, probably due to
      mitochondrial dysfunction. Concordantly, mitochondrial fission in response to
      nutrient stimuli was abolished with downregulation of Bnip3 and phospho-Drp1 in
      the hepatocytes of RORalpha-LKO. RORalpha enhanced oxygen consumption rate and
      expression of genes associated with mitochondrial quality control. Finally, we
      observed the positive correlation of the expression levels of Bnip3 and PGC
      1alpha with those of RORalpha in patients with steatohepatitis. Together, we
      demonstrated that RORalpha mediates mitochondrial quality under nutrient
      overloaded conditions and propose RORalpha as a potential therapeutic target in
      treatment of NASH.

PMID- 29167530
TI  - High-density native-range species affects the invasive plant Chromolaena odorata
      more strongly than species from its invasive range.
AB  - Invasive plant species often form dense mono-dominant stands in areas they have
      invaded, while having only sparse distribution in their native ranges, and the
      reasons behind this phenomenon are a key point of research in invasive species
      biology. Differences in species composition between native and invasive ranges
      may contribute to the difference in distribution status. In this study, we found
      that the high-density condition had a more negative effect on C. odorata than the
      low-density condition when co-grown with neighbor plants from its native range in
      Mexico, while this pattern was not in evidence when it was grown with neighbors
      from its invasive range in China. Different competitive ability and
      coevolutionary history with C. odorata between native-range neighbors and
      invasive-range neighbors may lead to the inconsistent patterns.

PMID- 29167531
TI  - Publisher Correction: Sex-Dependent Effects of Caloric Restriction on the Ageing
      of an Ambush Feeding Copepod.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29167532
TI  - Long-Read Sequencing of Human Cytomegalovirus Transcriptome Reveals RNA Isoforms
      Carrying Distinct Coding Potentials.
AB  - The human cytomegalovirus (HCMV) is a ubiquitous, human pathogenic herpesvirus.
      The complete viral genome is transcriptionally active during infection; however,
      a large part of its transcriptome has yet to be annotated. In this work, we
      applied the amplified isoform sequencing technique from Pacific Biosciences to
      characterize the lytic transcriptome of HCMV strain Towne varS. We developed a
      pipeline for transcript annotation using long-read sequencing data. We identified
      248 transcriptional start sites, 116 transcriptional termination sites and 80
      splicing events. Using this information, we have annotated 291 previously
      undescribed or only partially annotated transcript isoforms, including eight
      novel antisense transcripts and their isoforms, as well as a novel transcript
      (RS2) in the short repeat region, partially antisense to RS1. Similarly to other
      organisms, we discovered a high transcriptional diversity in HCMV, with many
      transcripts only slightly differing from one another. Comparing our transcriptome
      profiling results to an earlier ribosome footprint analysis, we have concluded
      that the majority of the transcripts contain multiple translationally active
      ORFs, and also that most isoforms contain unique combinations of ORFs. Based on
      these results, we propose that one important function of this transcriptional
      diversity may be to provide a regulatory mechanism at the level of translation.

PMID- 29167533
TI  - Muscle MRI and functional outcome measures in Becker muscular dystrophy.
AB  - Becker muscular dystrophy (BMD) is a neuromuscular disorder allelic to Duchenne
      muscular dystrophy (DMD), caused by in-frame mutations in the dystrophin gene,
      and characterized by a clinical progression that is both milder and more
      heterogeneous than DMD. Muscle magnetic resonance imaging (MRI) has been proposed
      as biomarker of disease progression in dystrophinopathies. Correlation with
      clinically meaningful outcome measures such as North Star Ambulatory Assessment
      (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In
      this study, 51 molecularly confirmed BMD patients (aged 7-69 years) underwent
      muscle MRI and were evaluated with functional measures (NSAA and 6MWT) at the
      time of the MRI, and subsequently after one year. We confirmed a pattern of fatty
      substitution involving mainly the hip extensors and most thigh muscles. Severity
      of muscle fatty substitution was significantly correlated with specific DMD
      mutations: in particular, patients with an isolated deletion of exon 48, or
      deletions bordering exon 51, showed milder involvement. Fat infiltration scores
      correlated with baseline functional measures, and predicted changes after 1 year.
      We conclude that in BMD, skeletal muscle MRI not only strongly correlates with
      motor function, but also helps in predicting functional deterioration within a 12
      month time frame.

PMID- 29167534
TI  - Declining pre-monsoon dust loading over South Asia: Signature of a changing
      regional climate.
AB  - Desert dust over the Indian region during pre-monsoon season is known to
      strengthen monsoon circulation, by modulating rainfall through the elevated heat
      pump (EHP) mechanism. In this context, an insight into long term trends of dust
      loading over this region is of significant importance in understanding monsoon
      variability. In this study, using long term (2000 to 2015) aerosol measurements
      from multiple satellites, ground stations and model based reanalysis, we show
      that dust loading in the atmosphere has decreased by 10 to 20% during the pre
      monsoon season with respect to start of this century. Our analysis reveals that
      this decrease is a result of increasing pre-monsoon rainfall that in turn
      increases (decreases) wet scavenging (dust emissions) and slowing circulation
      pattern over the Northwestern part of the sub-continent.

PMID- 29167536
TI  - Energy expenditure estimation from respiration variables.
AB  - The aim of this study was to develop and cross-validate two models to estimate
      total energy expenditure (TEE) based on respiration variables in healthy subjects
      during daily physical activities. Ninety-nine male and female subjects
      systematically varying in age (18-60 years) and body mass index (BMI; 17-36 kg*m
      2) completed eleven aerobic activities with a portable spirometer as the
      criterion measure. Two models were developed using linear regression analyses
      with the data from 67 randomly selected subjects (50.0% female, 39.9 +/- 11.8
      years, 25.1 +/- 5.2 kg*m-2). The models were cross-validated with the other 32
      subjects (49% female, 40.4 +/- 10.7 years, 24.7 +/- 4.6 kg*m-2) by applying
      equivalence testing and Bland-and-Altman analyses. Model 1, estimating TEE based
      solely on respiratory volume, respiratory rate, and age, was significantly
      equivalent to the measured TEE with a systematic bias of 0.06 kJ*min-1 (0.22%)
      and limits of agreement of +/-6.83 kJ*min-1. Model 1 was as accurate in
      estimating TEE as Model 2, which incorporated further information on activity
      categories, heart rate, sex, and BMI. The results demonstrated that respiration
      variables and age can be used to accurately determine daily TEE for different
      types of aerobic activities in healthy adults across a broad range of ages and
      body sizes.

PMID- 29167535
TI  - Transcriptomic profiling of Alternaria longipes invasion in tobacco reveals
      pathogenesis regulated by AlHK1, a group III histidine kinase.
AB  - Tobacco brown spot, caused by Alternaria species, is a devastating tobacco
      disease. To explore the role of a group III histidine kinase (AlHK1) on A.
      longipes pathogenesis, the invasion progress of A. longipes was monitored. We
      found that the wild-type strain C-00 invaded faster than the AlHK1-disrupted
      strain HK?4 in the early and middle infection stages and the reverse trend
      occurred in the late infection stage. Then, eight invasion transcriptomes were
      performed using RNA-Seq and 205 shared, 505 C-00 and 222 HK?4 specific
      differentially expressed genes (DEGs) were identified. The annotation results
      showed seven antioxidant activity genes were specifically identified in the
      HKDelta4 DEGs. A subsequent experiment confirmed that HKDelta4 was more resistant
      to low concentrations oxidative stress than C-00. In addition, the results from
      1) statistics for the number of DEGs, GO enriched terms, DEGs in clusters with
      rising trends, and 2) analyses of the expression patterns of some DEGs relevant
      for osmoadaptation and virulence showed that changes in C-00 infection existed
      mainly in the early and middle stages, while HKDelta4 infection arose mainly in
      the late stage. Our results reveal firstly the pathogenesis of A. longipes
      regulated by AlHK1 and provide useful insights into the fungal-plant
      interactions.

PMID- 29167537
TI  - Publisher Correction: Use of RNAi technology to develop a PRSV-resistant
      transgenic papaya.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29167538
TI  - A Deep-Dream Virtual Reality Platform for Studying Altered Perceptual
      Phenomenology.
AB  - Altered states of consciousness, such as psychotic or pharmacologically-induced
      hallucinations, provide a unique opportunity to examine the mechanisms underlying
      conscious perception. However, the phenomenological properties of these states
      are difficult to isolate experimentally from other, more general physiological
      and cognitive effects of psychoactive substances or psychopathological
      conditions. Thus, simulating phenomenological aspects of altered states in the
      absence of these other more general effects provides an important experimental
      tool for consciousness science and psychiatry. Here we describe such a tool,
      which we call the Hallucination Machine. It comprises a novel combination of two
      powerful technologies: deep convolutional neural networks (DCNNs) and panoramic
      videos of natural scenes, viewed immersively through a head-mounted display
      (panoramic VR). By doing this, we are able to simulate visual hallucinatory
      experiences in a biologically plausible and ecologically valid way. Two
      experiments illustrate potential applications of the Hallucination Machine.
      First, we show that the system induces visual phenomenology qualitatively similar
      to classical psychedelics. In a second experiment, we find that simulated
      hallucinations do not evoke the temporal distortion commonly associated with
      altered states. Overall, the Hallucination Machine offers a valuable new
      technique for simulating altered phenomenology without directly altering the
      underlying neurophysiology.

PMID- 29167539
TI  - Genome-wide analysis shows that RNase G plays a global role in the stability of
      mRNAs in Stenotrophomonas maltophilia.
AB  - Gene expression is determined by critical processes such as RNA synthesis and
      degradation. Ribonucleases participate in the coordinated and differential decay
      of messenger RNAs. We describe a suitable method of normalization and calculation
      of mRNAs half-life values quantified by RNA-Seq. We determined the mRNA half
      lives of more than 2000 genes in Stenotrophomonas maltophilia D457 and in an
      isogenic RNase G deficient mutant. Median half-lives were 2,74 and 3 min in the
      wild-type and the rng-deficient strain, respectively. The absence of RNase G
      resulted in an overall enhancement of mRNA half-life times, showing that many
      RNAs are targets of RNase G in S. maltophilia. Around 40 genes are likely to be
      regulated directly by RNase G since their half-lives were more than two-fold
      higher in the rng-deficient mutant. Gene length, GC content or expression levels
      did not correlate with mRNAs lifetimes, although groups of genes with different
      functions showed different RNA half-lives. Further, we predicted 1542 gene pairs
      to be part of the same operons in S. maltophilia. In contrast to what was
      described for other bacteria, our data indicate that RNase G has a global role in
      mRNA stability and consequently in the regulation of S. maltophilia gene
      expression.

PMID- 29167540
TI  - Water and Blood Repellent Flexible Tubes.
AB  - A top-down scalable method to produce flexible water and blood repellent tubes is
      introduced. The method is based on replication of overhanging nanostructures from
      an aluminum tube template to polydimethylsiloxane (PDMS) via atomic layer
      deposition (ALD) assisted sacrificial etching. The nanostructured PDMS/titania
      tubes are superhydrophobic with water contact angles 163 +/- 1 degrees 
      (advancing) and 157 +/- 1 degrees  (receding) without any further coating.
      Droplets are able to slide through a 4 mm (inner diameter) tube with low sliding
      angles of less than 10 degrees  for a 35 uL droplet. The superhydrophobic tube
      shows up to 5,000 times increase in acceleration of a sliding droplet compared to
      a control tube depending on the inclination angle. Compared to a free falling
      droplet, the superhydrophobic tube reduced the acceleration by only 38.55%, as
      compared to a 99.99% reduction for a control tube. The superhydrophobic tubes are
      blood repellent. Blood droplets (35 uL) roll through the tubes at 15 degrees 
      sliding angles without leaving a bloodstain. The tube surface is resistant to
      adhesion of activated platelets unlike planar control titania and smooth PDMS
      surfaces.

PMID- 29167541
TI  - Effect of post-cessation hyperglycemia on cardiovascular disease and mortality
      among middle-aged men: an eight-year longitudinal study.
AB  - Smoking cessation reduces the risk of cardiovascular disease (CVD), but also
      elevates fasting serum glucose (FSG) levels. The effect of post-cessation
      hyperglycemia on cardiovascular disease is unknown. The study population
      consisted of 127,066 men without type 2 diabetes from the Korean National Health
      Insurance System - Health Screening Cohort database. Change in smoking habits and
      FSG was determined by the difference in smoking status and FSG levels from the
      first (2002 and 2003) and second (2004 and 2005) health examinations. Continual
      smokers, quitters, ex-smokers, and never smokers were stratified according to FSG
      elevation. The study participants were followed-up for CVD and CVD-related death
      from 2006 to 2013. Compared to continual smokers, quitters had decreased risk of
      CVD among those without FSG elevation (hazard ratio, HR, 0.76, 95% confidence
      interval, CI, 0.66-0.86) and with FSG elevation (HR 0.83, 95% CI 0.72-0.96).
      Similarly, quitters had a tendency towards reduced risk of CVD-related death
      among those without FSG elevation (HR 0.74, 95% CI 0.51-1.09) and with FSG
      elevation (HR 0.68, 95% CI 0.46-1.03). Post-cessation hyperglycemia did not
      attenuate the beneficiary risk-reducing effects of quitting on CVD and CVD
      related death.

PMID- 29167543
TI  - The role of reproductive isolation in allopolyploid speciation patterns:
      empirical insights from the progenitors of common wheat.
AB  - The ability to cause reproductive isolation often varies among individuals within
      a plant species. We addressed whether such polymorphism influenced speciation of
      the allopolyploid common wheat (Triticum aestivum L., AABBDD genome) by
      evaluating the expression of pre-pollination (outcrossing potential) and post
      pollination (crossability) barriers in Aegilops tauschii Coss. (the D genome
      progenitor). In total, 201 Ae. tauschii accessions representing the entire
      natural habitat range of the species were used for anther length measurement and
      artificial crosses with a Triticum turgidum L. (the AB genome progenitor) tester.
      Intraspecific comparisons showed that both barriers were more strongly expressed
      in the TauL1 lineage than in the TauL2 lineage. The ability of Ae. tauschii to
      cause reproductive isolation in the hybridisation with T. turgidum might have
      markedly influenced common wheat's speciation by inducing lineage-associated
      patterns of gene flow. The TauL2 accessions with high potential for natural
      hybridisation with T. turgidum clustered in the southern coastal Caspian region.
      This provided phenotypic support for the derivation of the D genome of common
      wheat from southern Caspian populations. The present study underscored the
      importance of approaches that incorporate the genealogical and geographic
      structure of the parental species' reproductive isolation in understanding the
      mechanism of plant allopolyploid speciation.

PMID- 29167544
TI  - Rheumatoid arthritis: Tocilizumab prevents progression of bone erosions.

PMID- 29167542
TI  - Telomerase activity is required for the telomere G-overhang structure in
      Trypanosoma brucei.
AB  - Trypanosoma brucei causes fatal human African trypanosomiasis and evades the host
      immune response by regularly switching its major surface antigen, VSG, which is
      expressed exclusively from subtelomeric loci. Telomere length and telomere
      proteins play important roles in regulating VSG silencing and switching. T.
      brucei telomerase plays a key role in maintaining telomere length, and T. brucei
      telomeres terminate in a single-stranded 3' G-rich overhang. Understanding the
      detailed structure of the telomere G-overhang and its maintenance will contribute
      greatly to better understanding telomere maintenance mechanisms. Using an
      optimized adaptor ligation assay, we found that most T. brucei telomere G
      overhangs end in 5' TTAGGG 3', while a small portion of G-overhangs end in 5'
      TAGGGT 3'. Additionally, the protein and the RNA components of the telomerase
      (TbTERT and TbTR) and TbKu are required for telomere G-overhangs that end in 5'
      TTAGGG 3' but do not significantly affect the 5' TAGGGT 3'-ending overhangs,
      indicating that telomerase-mediated telomere synthesis is important for the
      telomere G-overhang structure. Furthermore, using telomere oligo ligation
      mediated PCR, we showed for the first time that the T. brucei telomere 5' end
      sequence - an important feature of the telomere terminal structure - is not
      random but preferentially 5' CCTAAC 3'.

PMID- 29167545
TI  - Systemic lupus erythematosus: Effects of disease activity on pregnancy outcomes.

PMID- 29167546
TI  - Osteoporosis: Teriparatide preferable for fracture prevention.

PMID- 29167547
TI  - Crystal arthritis: Stepping up febuxostat to treat gout flares.

PMID- 29167548
TI  - Click chemistry-based tracking reveals putative cell wall-located auxin binding
      sites in expanding cells.
AB  - Auxin is a key plant regulatory molecule, which acts upon a plethora of cellular
      processes, including those related to cell differentiation and elongation.
      Despite the stunning progress in all disciplines of auxin research, the
      mechanisms of auxin-mediated rapid promotion of cell expansion and underlying
      rearrangement of cell wall components are poorly understood. This is partly due
      to the limitations of current methodologies for probing auxin. Here we describe a
      click chemistry-based approach, using an azido derivative of indole-3-propionic
      acid. This compound is as an active auxin analogue, which can be tagged in situ.
      Using this new tool, we demonstrate the existence of putative auxin binding sites
      in the cell walls of expanding/elongating cells. These binding sites are of
      protein nature but are distinct from those provided by the extensively studied
      AUXIN BINDING PROTEIN 1 (ABP1). Using immunohistochemistry, we have shown the
      apoplastic presence of endogenous auxin epitopes recognised by an anti-IAA
      antibody. Our results are intriguingly in line with previous observations
      suggesting some transcription-independent (non-genomic) activity of auxin in cell
      elongation.

PMID- 29167549
TI  - Highly (001)-textured p-type WSe2 Thin Films as Efficient Large-Area
      Photocathodes for Solar Hydrogen Evolution.
AB  - Highly (001)-textured, photoactive WSe2 thin films have been prepared by an
      amorphous solid-liquid-crystalline solid process promoted by palladium. By
      increasing the thickness of the Pd promoter film (>=10 nm) the structure and
      texture of the WSe2 films can be improved significantly. However, these as
      crystallized WSe2 films are only weakly photoactive in a 0.5 M H2SO4 electrolyte
      under AM 1.5 solar irradiation which we attribute to an inefficient
      photogenerated charge transfer across the WSe2/electrolyte interface via the
      prevailing van der Waals planes of the WSe2 crystallites. In this work
      photochemically deposited platinum on the p-type WSe2 photocathode is used for an
      efficient electron transfer thus inducing the hydrogen evolution reaction. Upon
      illuminating the WSe2 photocathodes in a Pt-ion containing electrolyte, the
      photogenerated electrons reduce Pt+ to Pt leading to the precipitation of Pt
      islands, preferentially at edge steps of the WSe2, i.e. at the grain boundaries
      of the WSe2 crystallites. The increasing amount of Pt islands at the grain
      boundaries linearly enhances the photocurrent density up to 2.5 mA cm-2 at 0 VRHE
      in sulfuric acid, the highest reported value up to now for WSe2 thin films.

PMID- 29167550
TI  - Speeding up bioproduction of selenium nanoparticles by using Vibrio natriegens as
      microbial factory.
AB  - Selenium and selenium nanoparticles (SeNPs) are extensively used in biomedicine,
      electronics and some other industrial applications. The bioproduction of SeNPs is
      gaining interest as a green method to manufacture these biotechnologically
      relevant products. Several microorganisms have been used for the production of
      SeNPs either under aerobic or anaerobic conditions. Vibrio natriegens is a non
      pathogenic fast-growing bacterium, easily cultured in different carbon sources
      and that has recently been engineered for easy genetic manipulation in the
      laboratory. Here we report that V. natriegens was able to perfectly grow
      aerobically in the presence of selenite concentrations up to 15 mM with a
      significant survival still observed at concentrations as high as 100 mM selenite.
      Electron microscopy and X-ray spectroscopy analyses demonstrate that V.
      natriegens cells growing aerobically in selenite-containing LB medium at 30 
      degrees C produced spherical electron-dense SeNPs whose size ranged from 100-400
      nm. Selenite reduction just started at the beginning of the exponential growth
      phase and the release of SeNPs was observed after cell lysis. Remarkably, V.
      natriegens produced SeNPs faster than other described microorganisms that were
      proposed as model bioreactors for SeNPs production. Thus, the fast-growing V.
      natriegens bacterium becomes a suitable biocatalyst for bioremediation of
      selenite and for speeding-up the eco-friendly synthesis of SeNPs.

PMID- 29167551
TI  - A novel SNP in promoter region of RP11-3N2.1 is associated with reduced risk of
      colorectal cancer.
AB  - Single-nucleotide polymorphisms (SNPs) in the promoter region of long intergenic
      non-coding RNAs (lincRNAs) could play a regulatory role in its expression level
      and then get involved in colorectal cancer (CRC). Thus, we conducted a two-stage
      case-control study to investigate the associations of Tag SNPs within the
      promoter region of selected lincRNAs from microarray data with risk of CRC. A
      total of 320 cases and 319 controls were recruited in the test set to explore the
      associations between 16 SNPs with no deviations from Hardy-Weinberg equilibrium
      (HWE) and risk of CRC. Furthermore, 501 cases and 538 controls were included as
      the validation set to confirm the significant associations. RP11-3N2.1 rs13230517
      polymorphism was found to be negatively associated with CRC in both test set (AA
      vs. GG, OR = 0.68, 95% CI = 0.48-0.96) and validation set (AA vs. GG, OR = 0.76,
      95% CI = 0.59-0.98). Pooled analysis showed that individuals with GA/AA genotypes
      had a significantly decreased risk of CRC when compared with those carrying GG
      genotype (OR = 0.74, 95% CI = 0.60-0.90) in the combined set. The crossover
      analysis revealed that rs13230517 GA/AA carriers had a decreased risk of CRC than
      GG carriers among non-drinkers in both test and combined set. However, no gene
      environment multiplicative interactions were found on risk of CRC. Our findings
      suggest that rs13230517 polymorphism might participate in the pathogenesis of CRC
      and have the potential to be a biomarker for predicting the risk of CRC.

PMID- 29167552
TI  - Association of ETS1 polymorphism with granulomatosis with polyangiitis and
      proteinase 3-anti-neutrophil cytoplasmic antibody positive vasculitis in a
      Japanese population.
AB  - ETS proto-oncogene 1, transcription factor (ETS1) is involved in various immune
      responses. Genome-wide association studies on systemic lupus erythematosus in
      Chinese populations identified the association of ETS1 polymorphism in 3'
      untranslated region, rs1128334A, which was associated with lower ETS1 expression.
      In view of substantial sharing of susceptibility genes across multiple autoimmune
      diseases, we examined whether ETS1 is associated with a rare autoimmune rheumatic
      disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
      Association of rs1128334 was tested in 466 Japanese patients with AAV and 1099
      healthy controls by logistic regression analysis under the additive model. AAV
      patients were classified into 285 microscopic polyangiitis (MPA), 92
      granulomatosis with polyangiitis (GPA), 56 eosinophilic GPA, and 33
      unclassifiable AAV, according to the European Medicines Agency (EMEA) algorithm.
      Among the patients, 376 were positive for MPO-ANCA and 62 for PR3-ANCA. When the
      patients were classified according to the EMEA classification, rs1128334A allele
      was significantly increased in GPA (P = 0.0060, P c = 0.030, odds ratio (OR),
      1.54; 95% confidence interval (CI), 1.13-2.10). With respect to the ANCA
      specificity, significant association was observed in PR3-ANCA positive AAV (P =
      0.0042, P c = 0.021, OR, 1.72; 95% CI, 1.19-2.49). In conclusion, ETS1
      polymorphism was suggested to be associated with GPA and PR3-ANCA positive AAV in
      a Japanese population.

PMID- 29167553
TI  - Updated summary of genome editing technology in human cultured cells linked to
      human genetics studies.
AB  - Current deep-sequencing technology provides a mass of nucleotide variations
      associated with human genetic disorders to accelerate the identification of
      causative mutations. To understand the etiology of genetic disorders, reverse
      genetics in human cultured cells is a useful approach for modeling a disease in
      vitro. However, gene targeting in human cultured cells is difficult because of
      their low activity of homologous recombination. Engineered endonucleases enable
      enhancement of the local activation of DNA repair pathways at the human genome
      target site to rewrite the desired sequence, thereby efficiently generating
      disease-modeling cultured cell clones. These edited cells can be used to explore
      the molecular functions of a causative gene product to uncover the etiological
      mechanisms. The correction of mutations in patient cells using genome editing
      technology could contribute to the development of unique gene therapies. This
      technology can also be applied to screening causative mutations. Rare genetic
      disorders and non-exonic mutation-caused diseases remain frontier in the field of
      human genetics as it is difficult to validate whether the extracted nucleotide
      variants are mutation or polymorphism. When isogenic human cultured cells with a
      candidate variant reproduce the pathogenic phenotypes, it is confirmed that the
      variant is a causative mutation.

PMID- 29167554
TI  - Phenotypic expression of a novel desmin gene mutation: hypertrophic
      cardiomyopathy followed by systemic myopathy.
AB  - Hypertrophic cardiomyopathy is a heterogeneous disease caused by gene mutations.
      Most of the disease-causing mutations were found in the genes for sarcomeric
      proteins, but there are several cases carrying mutations in genes for extra
      sarcomeric cytoskeletons. Desmin is a member of extra-sarcomeric cytoskeletons
      and plays an important role in muscle contraction. Mutations in the desmin gene
      cause various type of general myopathy and/or cardiomyopathy, known as desmin
      related myopathies. We identified a novel desmin missense mutation, Thr219Pro, in
      the homozygous state in a patient, who first manifested with hypertrophic
      cardiomyopathy and later progressed to general myopathy. His parents were
      heterozygous for the mutation, but showed no clinical abnormality, suggesting the
      recessive inheritance of the mutation. We here report a severe phenotype of
      hypertrophic cardiomyopathy preceded the onset of general myopathy caused by a
      novel homozygous missense mutation in the 1B alpha-helix domain of desmin.

PMID- 29167555
TI  - Efficacy and safety of low dose alteplase for intravenous thrombolysis in Asian
      stroke patients: a meta-analysis.
AB  - Whether low dose alteplase is comparable to standard dose in efficacy and safety
      for intravenous thrombolysis (IVT) in Asian stroke patients remains unverified.
      PubMed, EMBASE, and Cochrane Library Database from the beginning to June 30, 2017
      were searched. IVT efficacy was measured by favorable outcome (modified Rankin
      Scale scores of 0-1) at 3 months, and safety measured by mortality within 3
      months and symptomatic intracerebral hemorrhage (SICH). Pooled estimates were
      conducted using fixed- or random-effects model depending on heterogeneity. For
      SICH, studies were pooled separately according to different definitions. Twelve
      studies involving 7,905 participants were included. No association was found
      between alteplase dose and favorable outcome (OR = 0.94, 95% CI 0.78-1.14, P =
      0.5; heterogeneity: P hetero  = 0.01, I2 = 57.3%) and mortality (OR = 0.87, 95%
      CI 0.74-1.02, P = 0.08; P hetero  = 0.83, I2 = 0) using random- and fixed-effects
      models, respectively. Low dose alteplase was associated with lower SICH as
      defined by the National Institute of Neurological Disorders and Stroke study (OR
      = 0.79, 95% CI 0.64-0.99, P = 0.04; P hetero  = 0.57, I2 = 0) using fixed-effects
      model. Subgroup and sensitivity analysis could change the results significantly.
      Current limited evidence was insufficient to support the speculation that low
      dose alteplase was comparable to standard dose in thrombolytic efficacy and
      safety in Asian stroke patients.

PMID- 29167556
TI  - Alterations in gut microbiota associated with a cafeteria diet and the
      physiological consequences in the host.
AB  - OBJECTIVE: Gut microbiota have been described as key factors in the
      pathophysiology of obesity and different components of metabolic syndrome (MetS).
      The cafeteria diet (CAF)-fed rat is a preclinical model that reproduces most of
      the alterations found in human MetS by simulating a palatable human unbalanced
      diet. Our objective was to assess the effects of CAF on gut microbiota and their
      associations with different components of MetS in Wistar rats. METHODS: Animals
      were fed a standard diet or CAF for 12 weeks. A partial least square-based
      methodology was used to reveal associations between gut microbiota, characterized
      by 16S ribosomal DNA gene sequencing, and biochemical, nutritional and
      physiological parameters. RESULTS: CAF feeding resulted in obesity, dyslipidemia,
      insulin resistance and hepatic steatosis. These changes were accompanied by a
      significant decrease in gut bacterial diversity, decreased Firmicutes and an
      increase in Actinobacteria and Proteobacteria abundances, which were concomitant
      with increased endotoxemia. Associations of different genera with the intake of
      lipids and carbohydrates were opposed from those associated with the intake of
      fiber. Changes in gut microbiota were also associated with the different
      physiological effects of CAF, mainly increased adiposity and altered levels of
      plasma leptin and glycerol, consistent with altered adipose tissue metabolism.
      Also hepatic lipid accretion was associated with changes in microbiota,
      highlighting the relevance of gut microbiota homeostasis in the adipose-liver
      axis. CONCLUSIONS: Overall, our results suggest that CAF feeding has a profound
      impact on the gut microbiome and, in turn, that these changes may be associated
      with important features of MetS.

PMID- 29167557
TI  - Factors affecting GEBV accuracy with single-step Bayesian models.
AB  - A single-step approach to obtain genomic prediction was first proposed in 2009.
      Many studies have investigated the components of GEBV accuracy in genomic
      selection. However, it is still unclear how the population structure and the
      relationships between training and validation populations influence GEBV accuracy
      in terms of single-step analysis. Here, we explored the components of GEBV
      accuracy in single-step Bayesian analysis with a simulation study. Three
      scenarios with various numbers of QTL (5, 50, and 500) were simulated. Three
      models were implemented to analyze the simulated data: single-step genomic best
      linear unbiased prediction (GBLUP; SSGBLUP), single-step BayesA (SS-BayesA), and
      single-step BayesB (SS-BayesB). According to our results, GEBV accuracy was
      influenced by the relationships between the training and validation populations
      more significantly for ungenotyped animals than for genotyped animals. SS
      BayesA/BayesB showed an obvious advantage over SSGBLUP with the scenarios of 5
      and 50 QTL. SS-BayesB model obtained the lowest accuracy with the 500 QTL in the
      simulation. SS-BayesA model was the most efficient and robust considering all QTL
      scenarios. Generally, both the relationships between training and validation
      populations and LD between markers and QTL contributed to GEBV accuracy in the
      single-step analysis, and the advantages of single-step Bayesian models were more
      apparent when the trait is controlled by fewer QTL.

PMID- 29167558
TI  - Recurring Amplification at 11q22.1-q22.2 Locus Plays an Important Role in Lymph
      Node Metastasis and Radioresistance in OSCC.
AB  - A key feature in the pathogenesis of OSCC is genetic instability, which results
      in altered expression of genes located in amplified/deleted chromosomal regions.
      In a previous study we have shown that the amplification of the 11q22.1-q22.2
      region, encoding cIAP1 and cIAP2, is associated with lymph node metastasis and
      poor clinical outcome in OSCC. Here, we validate the aCGH results by nuc ish and
      detect a weak amplification at the 11q22.1-q22.2 locus in 37% of the 182 samples
      tested. We find positive correlation of 11q22.1-q22.2 amplification with lymph
      node metastasis, reduced survival, and increased cancer recurrence, and we
      observe that patients with 11q22.1-q22.2 amplification fail to respond to
      radiotherapy. We confirm the concurrent overexpression of cIAP1 and cIAP2 and
      observe differential subcellular localization of the two proteins in OSCC. To
      ascertain the roles of cIAP1/cIAP2 in lymph node metastasis and radioresistance,
      we use an in vitro pre-clinical model and confirm the role of cIAP1 in invasion
      and the role of cIAP2 in invasion and migration. Studies of other tumor types in
      which cIAP1 is overexpressed suggest that multi-regimen treatments including SMAC
      mimetics may be effective. Thus, the evaluation of 11q22.1-q22.2 amplifications
      in OSCC patients may help choose the most effective treatment.

PMID- 29167559
TI  - Au19M (M=Cr, Mn, and Fe) as magnetic copies of the golden pyramid.
AB  - An investigation on structure, stability, and magnetic properties of singly doped
      Au19M (M=Cr, Mn, and Fe) clusters is carried out by means of density functional
      theory calculations. The studied clusters prefer forming magnetic versions of the
      unique tetrahedral Au20. Stable sextet Au19Cr is identified as the least reactive
      species and can be qualified as a magnetic superatom. Analysis on cluster
      electronic structures shows that the competition between localized and
      delocalized electronic states governs the stability and magnetic properties of
      Au19M clusters.

PMID- 29167560
TI  - Transcriptome responses of Streptococcus mutans to peroxide stress:
      identification of novel antioxidant pathways regulated by Spx.
AB  - The oxidative stress regulator Spx is ubiquitously found among Gram-positive
      bacteria. Previously, we reported identification of two Spx proteins in
      Streptococcus mutans - SpxA1 was the primary activator of oxidative stress genes
      whereas SpxA2 served a backup role. Here, we used RNA sequencing to uncover the
      scope of the H2O2 (peroxide)-stress regulon and to further explore the
      significance of Spx regulation in S. mutans. The transcriptome data confirmed the
      relationship between Spx and genes typically associated with oxidative stress,
      but also identified novel genes and metabolic pathways controlled by Spx during
      peroxide stress. While individual inactivation of newly identified peroxide
      stress genes had modest or no obvious consequences to bacterial survival, a
      phenotype enhancement screen using the ?spxA1 strain as background for creation
      of double mutants revealed that four of the five genes inactivated were required
      for stress survival. Physiological and biochemical assays validated, at least in
      part, the transcriptome data indicating that SpxA1 coordinates transcriptional
      changes during peroxide stress that modify global metabolism and facilitate
      production of antioxidants. Collectively, our findings unraveled the scope of the
      peroxide stress regulon and expand the repertoire of oxidative stress genes in S.
      mutans, shedding new light on the role of Spx regulation.

PMID- 29167561
TI  - Automated quantification of protein periodic nanostructures in fluorescence
      nanoscopy images: abundance and regularity of neuronal spectrin membrane
      associated skeleton.
AB  - Fluorescence nanoscopy imaging permits the observation of periodic supramolecular
      protein structures in their natural environment, as well as the unveiling of
      previously unknown protein periodic structures. Deciphering the biological
      functions of such protein nanostructures requires systematic and quantitative
      analysis of large number of images under different experimental conditions and
      specific stimuli. Here we present a method and an open source software for the
      automated quantification of protein periodic structures in super-resolved images.
      Its performance is demonstrated by analyzing the abundance and regularity of the
      spectrin membrane-associated periodic skeleton (MPS) in hippocampal neurons of 2
      to 40 days in vitro, imaged by STED and STORM nanoscopy. The automated analysis
      reveals that both the abundance and the regularity of the MPS increase over time
      and reach maximum plateau values after 14 DIV. A detailed analysis of the
      distributions of correlation coefficients provides indication of dynamical
      assembly and disassembly of the MPS.

PMID- 29167562
TI  - The directed evolution of ligand specificity in a GPCR and the unequal
      contributions of efficacy and affinity.
AB  - G protein-coupled receptors (GPCRs) must discriminate between hundreds of related
      signal molecules. In order to better understand how GPCR specificity can arise
      from a common promiscuous ancestor, we used laboratory evolution to invert the
      specificity of the Saccharomyces cerevisiae mating receptor Ste2. This GPCR
      normally responds weakly to the pheromone of the related species Kluyveromyces
      lactis, though we previously showed that mutation N216S is sufficient to make
      this receptor promiscuous. Here, we found that three additional substitutions,
      A265T, Y266F and P290Q, can act together to confer a novel specificity for K.
      lactis pheromone. Unlike wild-type Ste2, this new variant does not rely on
      differences in binding affinity to discriminate against its non-preferred ligand.
      Instead, the mutation P290Q is critical for suppressing the efficacy of the
      native pheromone. These two alternative methods of ligand discrimination were
      mapped to specific amino acid positions on the peptide pheromones. Our work
      demonstrates that changes in ligand efficacy can drive changes in GPCR
      specificity, thus obviating the need for extensive binding pocket re-modeling.

PMID- 29167563
TI  - Specification of murine ground state pluripotent stem cells to regional neuronal
      populations.
AB  - Pluripotent stem cells (PSCs) are a valuable tool for interrogating development,
      disease modelling, drug discovery and transplantation. Despite the burgeoned
      capability to fate restrict human PSCs to specific neural lineages, comparative
      protocols for mouse PSCs have not similarly advanced. Mouse protocols fail to
      recapitulate neural development, consequently yielding highly heterogeneous
      populations, yet mouse PSCs remain a valuable scientific tool as differentiation
      is rapid, cost effective and an extensive repertoire of transgenic lines provides
      an invaluable resource for understanding biology. Here we developed protocols for
      neural fate restriction of mouse PSCs, using knowledge of embryonic development
      and recent progress with human equivalents. These methodologies rely upon naive
      ground-state PSCs temporarily transitioning through LIF-responsive stage prior to
      neural induction and rapid exposure to regional morphogens. Neural subtypes
      generated included those of the dorsal forebrain, ventral forebrain, ventral
      midbrain and hindbrain. This rapid specification, without feeder layers or
      embryoid-body formation, resulted in high proportions of correctly specified
      progenitors and neurons with robust reproducibility. These generated neural
      progenitors/neurons will provide a valuable resource to further understand
      development, as well disorders affecting specific neuronal subpopulations.

PMID- 29167564
TI  - Whole Transcriptome Sequencing Analyses Reveal Molecular Markers of Blood
      Pressure Response to Thiazide Diuretics.
AB  - Thiazide diuretics (TD) are commonly prescribed anti-hypertensives worldwide.
      However, <40% of patients treated with thiazide monotherapy achieve BP control.
      This study uses whole transcriptome sequencing to identify novel molecular
      markers associated with BP response to TD. We assessed global RNA expression
      levels in whole blood samples from 150 participants, representing patients in the
      upper and lower quartile of BP response to TD from the Pharmacogenomic Evaluation
      of Antihypertensive Responses (PEAR) (50 whites) and from PEAR-2 (50 whites and
      50 blacks). In each study cohort, we performed poly-A RNA-sequencing in baseline
      samples from 25 responders and 25 non-responders to hydrochlorothiazide (HCTZ) or
      chlorthalidone. At FDR adjusted p-value < 0.05, 29 genes were differentially
      expressed in relation to HCTZ or chlorthalidone BP response in whites. For each
      differentially expressed gene, replication was attempted in the alternate white
      group and PEAR-2 blacks. CEBPD (meta-analysis p = 1.8 * 10-11) and TSC22D3 (p =
      1.9 * 10-9) were differentially expressed in all 3 cohorts, and explain, in
      aggregate, 21.9% of response variability to TD. This is the first report of the
      use of transcriptome-wide sequencing data to identify molecular markers of
      antihypertensive drug response. These findings support CEBPD and TSC22D3 as
      potential biomarkers of BP response to TD.

PMID- 29167565
TI  - Increased inflammation, oxidative stress and mitochondrial respiration in brown
      adipose tissue from obese mice.
AB  - Obesity is associated with severe metabolic diseases such as type 2 diabetes,
      insulin resistance, cardiovascular disease and some forms of cancer. The
      pathophysiology of obesity-induced metabolic diseases has been strongly related
      to white adipose tissue (WAT) dysfunction through several mechanisms such as
      fibrosis, apoptosis, inflammation, ER and oxidative stress. However, little is
      known of whether these processes are also present in brown adipose tissue (BAT)
      during obesity, and the potential consequences on mitochondrial activity. Here we
      characterized the BAT of obese and hyperglycemic mice treated with a high-fat
      diet (HFD) for 20 weeks. The hypertrophic BAT from obese mice showed no signs of
      fibrosis nor apoptosis, but higher levels of inflammation, ER stress, ROS
      generation and antioxidant enzyme activity than the lean counterparts. The
      response was attenuated compared with obesity-induced WAT derangements, which
      suggests that BAT is more resistant to the obesity-induced insult. In fact,
      mitochondrial respiration in BAT from obese mice was enhanced, with a 2-fold
      increase in basal oxygen consumption, through the upregulation of complex III of
      the electron transport chain and UCP1. Altogether, our results show that obesity
      is accompanied by an increase in BAT mitochondrial activity, inflammation and
      oxidative damage.

PMID- 29167566
TI  - Destructive influence of interlayer coupling on Heider balance in bilayer
      networks.
AB  - We consider the problem of Heider balance in a link multiplex, i.e. a special
      multiplex where coupling exists only between corresponding links. Numerical
      simulations and analytical calculations demonstrate that the presence of such
      interlayer connections hinders the emergence of the Heider balance. The effect is
      especially pronounced when the interactions between layers are negative,
      similarly as in antiferromagnetically coupled spin layers. The larger is the
      network, the narrower is the region of coupling parameters where the Heider
      balance can exist. If the interlayer couplings are of opposite signs and are
      strong enough, then the link dynamics can be reduced to the system of weakly
      coupled harmonic oscillators. For large strongly-coupled networks and randomly
      chosen initial conditions the probability of attaining the Heider balance
      decreases with the network size N as [Formula: see text]. Our finding can explain
      a lack of the Heider balance in many social systems, where multilayer structures
      mediate social interactions.

PMID- 29167567
TI  - Real-time in vivo imaging reveals localised Nrf2 stress responses associated with
      direct and metabolism-dependent drug toxicity.
AB  - The transcription factor Nrf2 coordinates an adaptive response to chemical and
      oxidative stress characterised by the upregulated expression of cytoprotective
      target genes. In order to understand the mechanistic relevance of Nrf2 as a
      marker of drug-induced stress it is important to know if this adaptive response
      is truly localised in the context of organ-specific drug toxicity. Here, we
      address this knowledge gap through real-time bioluminescence imaging of
      transgenic Nrf2-luciferase (Nrf2-luc) reporter mice following administration of
      the metabolism-dependent hepatotoxin acetaminophen (APAP) or the direct
      nephrotoxin cisplatin. We detected localised bioluminescence in the liver (APAP)
      and kidneys (cisplatin) in vivo and ex vivo, whilst qPCR, Taqman low-density
      array and immunoblot analysis of these tissues further revealed increases in the
      expression level of several endogenous Nrf2-regulated genes/proteins, including
      heme oxygenase 1 (Hmox1). Consistent with the toxic effects of APAP in the liver
      and cisplatin in the kidney, immunohistochemical analysis revealed the elevated
      expression of luciferase and Hmox1 in centrilobular hepatocytes and in tubular
      epithelial cells, respectively. In keeping with the role of reactive metabolite
      formation in APAP-induced chemical stress, both the hepatotoxicity and localised
      Nrf2-luc response were ameliorated by the cytochrome P450 inhibitor
      aminobenzotriazole. Together, these findings show that Nrf2 can reflect highly
      localised cellular perturbations associated with relevant toxicological
      mechanisms.

PMID- 29167568
TI  - Elite long jumpers with below the knee prostheses approach the board slower, but
      take-off more effectively than non-amputee athletes.
AB  - The use of technological aids to improve sport performance ('techno doping') and
      inclusion of Paralympic athletes in Olympic events are matters of ongoing debate.
      Recently, a long jumper with a below the knee amputation (BKA) achieved jump
      distances similar to world-class athletes without amputations, using a carbon
      fibre running-specific prosthesis (RSP). We show that athletes with BKA utilize a
      different, more effective take-off technique in the long jump, which provided the
      best athlete with BKA a performance advantage of at least 0.13 m compared to non
      amputee athletes. A maximum speed constraint imposed by the use of RSPs would
      indicate a performance disadvantage for the long jump. We found slower maximum
      sprinting speeds in athletes with BKA, but did not find a difference in the
      overall vertical force from both legs of athletes with BKA compared to non
      amputees. Slower speeds might originate from intrinsically lower sprinting
      abilities of athletes with BKA or from more complex adaptions in sprinting
      mechanics due to the biomechanical and morphological differences induced by RSPs.
      Our results suggest that due to different movement strategies, athletes with and
      without BKA should likely compete in separate categories for the long jump.

PMID- 29167570
TI  - Different protein-protein interface patterns predicted by different machine
      learning methods.
AB  - Different types of protein-protein interactions make different protein-protein
      interface patterns. Different machine learning methods are suitable to deal with
      different types of data. Then, is it the same situation that different interface
      patterns are preferred for prediction by different machine learning methods?
      Here, four different machine learning methods were employed to predict protein
      protein interface residue pairs on different interface patterns. The performances
      of the methods for different types of proteins are different, which suggest that
      different machine learning methods tend to predict different protein-protein
      interface patterns. We made use of ANOVA and variable selection to prove our
      result. Our proposed methods taking advantages of different single methods also
      got a good prediction result compared to single methods. In addition to the
      prediction of protein-protein interactions, this idea can be extended to other
      research areas such as protein structure prediction and design.

PMID- 29167569
TI  - Single-cell analysis reveals the continuum of human lympho-myeloid progenitor
      cells.
AB  - The hierarchy of human hemopoietic progenitor cells that produce lymphoid and
      granulocytic-monocytic (myeloid) lineages is unclear. Multiple progenitor
      populations produce lymphoid and myeloid cells, but they remain incompletely
      characterized. Here we demonstrated that lympho-myeloid progenitor populations in
      cord blood - lymphoid-primed multi-potential progenitors (LMPPs), granulocyte
      macrophage progenitors (GMPs) and multi-lymphoid progenitors (MLPs) - were
      functionally and transcriptionally distinct and heterogeneous at the clonal
      level, with progenitors of many different functional potentials present. Although
      most progenitors had the potential to develop into only one mature cell type
      ('uni-lineage potential'), bi- and rarer multi-lineage progenitors were present
      among LMPPs, GMPs and MLPs. Those findings, coupled with single-cell expression
      analyses, suggest that a continuum of progenitors execute lymphoid and myeloid
      differentiation, rather than only uni-lineage progenitors' being present
      downstream of stem cells.

PMID- 29167571
TI  - A windable and stretchable three-dimensional all-inorganic membrane for efficient
      oil/water separation.
AB  - There is strong interest in windable and stretchable membranes to meet the
      technological demands of practical water treatments. Oil/water separating
      membranes of this type is still significantly underdeveloped. Here, we reported a
      windable and stretchable membrane with three-dimensional structure for efficient
      oil/water separation. This membrane is made of ZnO nanorods arrays conformally
      grown on woven carbon microfibers. This three-dimensional architecture endows the
      fabricated membrane with highly windable and stretchable properties, at the same
      time ensures ZnO nanorods fully exposed outwards on the membrane surface. Due to
      its superior hydrophilicity and oleophobicity of ZnO nanorods, this all-inorganic
      membrane exhibits outstanding antifouling property, with the foulants on membrane
      surfaces easily removed by simple physical cleaning without chemicals. The
      membrane can effectively separate both oil/saline-water mixtures and oil-in-water
      emulsions, solely driven by gravity, with extremely high permeation flux of
      20933.4 L m-2 h-1 and high separation efficiency over 99%.

PMID- 29167572
TI  - Anti-Psl Targeting of Pseudomonas aeruginosa Biofilms for Neutrophil-Mediated
      Disruption.
AB  - Bacterial biofilms are recalcitrant to antibiotic therapy and a major cause of
      persistent and recurrent infections. New antibody-based therapies may offer
      potential to target biofilm specific components for host-cell mediated bacterial
      clearance. For Pseudomonas aeruginosa, human monoclonal antibodies (mAbs)
      targeting the Psl biofilm exopolysaccharide exhibit protective activity against
      planktonic bacteria in acute infection models. However, anti-Psl mAb activity
      against P. aeruginosa biofilms is unknown. Here, we demonstrate that anti-Psl
      mAbs targeting three distinct Psl epitopes exhibit stratified binding in mature
      in vitro biofilms and bind Psl within the context of a chronic biofilm infection.
      These mAbs also exhibit differential abilities to inhibit early biofilm events
      and reduce biomass from mature biofilms in the presence of neutrophils.
      Importantly, a mAb mixture with neutrophils exhibited the greatest biomass
      reduction, which was further enhanced when combined with meropenem, a common anti
      Pseudomonal carbapenem antibiotic. Moreover, neutrophil-mediated killing of
      biofilm bacteria correlated with the evident mAb epitope stratification within
      the biofilm. Overall, our results suggest that anti-Psl mAbs might be promising
      candidates for adjunctive use with antibiotics to inhibit/disrupt P. aeruginosa
      biofilms as a result of chronic infection.

PMID- 29167573
TI  - Metformin transiently inhibits colorectal cancer cell proliferation as a result
      of either AMPK activation or increased ROS production.
AB  - Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce
      cancer risk and improve the prognosis of certain malignancies. However, the
      mechanism underlying its anti-cancer effect is still unclear. We studied the anti
      cancer activity of metformin on colorectal cancer (CRC) by using the drug to
      treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin reduced cell
      proliferation and migration by inducing cell cycle arrest in the G0/G1 phase.
      This was accompanied by a sharp decrease in the expression of c-Myc and down
      regulation of IGF1R. The anti-proliferative action of metformin was mediated by
      two different mechanisms: AMPK activation and increase in the production of
      reactive oxygen species, which suppressed the mTOR pathway and its downstream
      targets S6 and 4EBP1. A reduction in CD44 and LGR5 expression suggested that the
      drug had an effect on tumour cells with stem characteristics. However, a colony
      formation assay showed that metformin slowed the cells' ability to form colonies
      without arresting cell growth, as confirmed by absence of apoptosis, autophagy or
      senescence. Our finding that metformin only transiently arrests CRC cell growth
      suggests that efforts should be made to identify compounds that combined with the
      biguanide can act synergistically to induce cell death.

PMID- 29167575
TI  - Nutritional assessment of critically ill patients: validation of the modified
      NUTRIC score.
AB  - BACKGROUND/OBJECTIVES: In order to identify critically ill patients with high
      nutritional risk the modified NUTrition Risk in the Critically ill (mNUTRIC)
      score was developed. This score aims to identify patients that will benefit from
      nutritional interventions. Few data are available on its validity. In The
      Netherlands, the MUST-score, a nutritional assessment tool for non-ICU patients,
      is commonly used in the ICU. To validate the mNUTRIC-score in Dutch ICU patients
      and compare its prognostic performance with the MUST-score. SUBJECTS/METHODS: A
      single-center retrospective cohort study among 475 mechanically ventilated
      patients. Prognostic performance of the mNUTRIC and MUST-scores were assessed and
      compared for discriminative abilities for 28-day mortality and prolonged
      mechanical ventilation (>2 days). RESULTS: The discriminative ability of the
      mNUTRIC-score for 28-day mortality is (ROC-AUC) 0.768 (95% CI 0.722-0.814) with
      an associated LR+ of 1.73 (95% CI 1.53-1.95) and LR- of 0.24 (95% CI 0.14-0.39)
      when comparing low with high (>4) scores. Comparing low with high MUST-scores
      (>1) a ROC-AUC of 0.513 (95% CI 0.445-0.587) and LR+ of 1.05 (95%CI 0.77-1.45)
      and LR- of 0.97 (95% CI 0.71-1.17) for mortality were found. The discriminative
      ability for prolonged ventilation was 0.666 (95% CI 0.616-0.716) and 0.532 (95%
      CI 0.469-0.594) for the mNUTRIC and MUST-scores, respectively. CONCLUSIONS: The
      prognostic performance of the mNUTRIC-score for 28-day mortality is fair and
      comparable to other validation studies. The association with prolonged
      ventilation was not confirmed by our results. The mNUTRIC-score has better
      performance than the commonly used MUST-score. Therefore, we suggest abandoning
      use of the MUST-score and to recommend introduction of the mNUTRIC-score for the
      nutritional risk assessment of critically ill patients.

PMID- 29167574
TI  - Structural basis of cholesterol binding by a novel clade of dendritic cell
      modulators from ticks.
AB  - Two crystal structures of Japanin, an 18 kDa immune-modulatory lipocalin from the
      Brown Ear Tick (Rhipicephalus appendiculatus), have been determined at 2.2 and
      2.4 A resolution. In both crystal forms the protein is in complex with
      cholesterol, which sits in a closed pocket at the centre of the lipocalin barrel.
      Both crystal forms are dimers, which are also observed in solution. Molecular
      modelling suggests that previously-described members of a tick protein family
      bearing high sequence homology to Japanin are also likely to bind cholesterol or
      cholesterol derivatives.

PMID- 29167576
TI  - The effect of weight change over a 2-year period on inflammatory status in
      postmenopausal women.
AB  - BACKGROUND/OBJECTIVES: Body fat distribution has been shown to be a predictor of
      adhesion molecule and inflammatory marker expression albeit the effect of modest
      weight change on concentrations of adhesion molecules and inflammatory markers in
      postmenopausal women are not fully understood. The primary aim was to investigate
      the effects of weight change on adhesion molecules and inflammatory markers over
      24 months in postmenopausal women. SUBJECTS/METHODS: Body composition was
      assessed in 254 healthy postmenopausal women using dual-energy X-ray
      absorptiometry (DXA). Adhesion molecules and inflammatory markers were analysed
      by multiplex ELISA. Participants weight gain/loss at 24 months was defined as any
      value that was either above/below the weight value recorded at baseline. RESULTS:
      Postmenopausal women with an average weight loss of 3% had significantly
      decreased leptin concentrations by 18% at 24 months (P < 0.01). A 4% increase in
      body weight or a 9% increase in FMI significantly increased intercellular
      adhesion molecule-1 (ICAM-1), tumour necrosis factor-alpha (TNF-alpha) and leptin
      concentrations in postmenopausal women at 24 months (P < 0.01). CONCLUSIONS:
      Modest weight loss in postmenopausal women has a lowering effect on leptin
      concentrations over 24 months which may improve inflammatory status whilst modest
      weight gain increases ICAM-1, leptin and TNF-alpha, markers which are associated
      with a pro-inflammatory state and vascular complications.

PMID- 29167577
TI  - Association of maternal breast milk and serum levels of macronutrients, hormones,
      and maternal body composition with infant's body weight.
AB  - BACKGROUND/OBJECTIVES: This study was aimed to investigate the association of
      maternal serum and breast-milk levels of macronutrients, hormones, growth
      factors, and maternal body composition with infant's body weight.
      SUBJECTS/METHODS: Eighty mother-infant pairs comprised 40 with overweight or
      obese infant and 40 with normal-weight infant were enrolled in this study. The
      level of ghrelin, Leptin, adiponectin, EGF, and IGF1 in plasma and breast milk
      were assessed. Daily breast milk intake and macronutrient concentration along
      with anthropometric indices of mother-infant pairs were also assessed. RESULTS:
      No significant differences were observed in concentrations of serum hormones
      between two groups (p > 0.05). However, hormones levels in maternal serum were
      higher than those in breast milk. A significant positive correlation was found
      between serum EGF and ghrelin (r = 0.57, p = 0 < 0001). Higher IGF1 in serum
      showed a significant association with its milk counterpart (r = 0.37). Current
      mother's weight was associated with infant's weight at the 2nd and 6th month (B =
      0.023 p = 0.04, B = 0.055 p = 0.005). The breast-milk macronutrient content was
      not comparable between two groups. However, the average daily breast milk
      consumption in obese infants was higher than normals (p = 0.001). Milk EGF and
      leptin were related to a decrease of 59% and 46% the odds of obese infant
      development, respectively. There was a significant association of milk EGF and
      ghrelin with birth weight (B = -0.19, p = 0.04 and B = -0.2, p = 0.04,
      respectively), and also serum leptin with infant's body weight at the 6th month.
      CONCLUSIONS: Our findings provide a positive association of maternal weight,
      daily breast milk intake, EGF, and ghrelin with infant's body weight.

PMID- 29167578
TI  - Comparative Genomics of Color Morphs In the Coral Montastraea cavernosa.
AB  - Montastraea cavernosa is a common coral in the Caribbean basin found in several
      color morphs. To investigate the causes for brown and orange morphs we undertook
      a genomics approach on corals collected at the same time and depth in the
      Bahamas. The coral holobiont includes the host, symbiotic dinoflagellates
      (Symbiodinium spp.), and a diverse microbiome. While the coral host showed
      significant genetic differentiation between color morphs both the composition of
      the Symbiodinium spp. communities and the prokaryotic communities did not. Both
      targeted and global gene expression differences in the transcriptome of the host
      show no difference in fluorescent proteins while the metatranscriptome of the
      microbiome shows that pigments such as phycoerythrin and orange carotenoid
      protein of cyanobacterial origin are significantly greater in orange morphs,
      which is also consistent with the significantly greater number of cyanobacteria
      quantified by 16S rRNA reads and flow cytometry. The microbiome of orange color
      morphs expressed significantly more nitrogenase (nifH) transcripts consistent
      with their known ability to fix nitrogen. Both coral and Symbiodinium spp.
      transcriptomes from orange morphs had significantly increased expression of genes
      related to immune response and apoptosis, which may potentially be involved in
      maintaining and regulating the unique symbiont population in orange morphs.

PMID- 29167579
TI  - The First 1000 Days of Life Factors Associated with "Childhood Asthma Symptoms":
      Brisa Cohort, Brazil.
AB  - This prospective study used data from the BRISA Cohort, Sao Luis, Brazil (n =
      1140) and analyzed associations between environmental factors up to the first
      1000 days of life and "Childhood Asthma Symptoms". "Childhood Asthma Symptoms"
      was a latent variable based on the number of wheezing episodes, emergency care
      visit due to wheezing, diagnosis of asthma and diagnosis of rhinitis. A
      theoretical model that included prenatal factors (socioeconomic status,
      pregestational body mass index-BMI, soft drink and junk food consumption), birth
      factors (gestational age, smoking and diseases during pregnancy, birth weight and
      type of delivery), first year of life factors (breastfeeding, environmental
      aeroallergens and respiratory diseases) and BMI z-score in the second year of
      life, was analyzed by structural equation modeling. High pregestational BMI, high
      soft drink consumption, cesarean section without labor, chill in the first three
      months of life, carpeted floor and child's exposure to tobacco were associated
      with higher values of "Childhood Asthma Symptoms". In contrast, high birth
      weight, breastfeeding and infant's age were associated with lower values of
      "Childhood Asthma Symptoms". These findings support the hypothesis that
      environmental factors that are present before conception and up to the first 1000
      days of life are associated with asthma.

PMID- 29167580
TI  - Pyridoxamine improves survival and limits cardiac dysfunction after MI.
AB  - Advanced glycation end products (AGEs) play a key role in the progression of
      heart failure. Whether treatments limiting AGEs formation would prevent adverse
      left ventricular remodeling after myocardial infarction (MI) remain unknown. We
      investigated whether pyridoxamine (PM) could limit adverse cardiac outcome in MI.
      Rats were divided into MI, MI + PM and Sham. Echocardiography and hemodynamic
      parameters were used to assess cardiac function 8 weeks post-surgery. Total
      interstitial collagen, collagen I and collagen III were quantified using Sirius
      Red and polarized light microscopy. PM improved survival following LAD occlusion.
      Pre-treatment with PM significantly decreased the plasma AGEs levels. MI rats
      treated with PM displayed reduced left ventricular end-diastolic pressure and tau
      compared to untreated MI rats. Deformation parameters were also improved with PM.
      The preserved diastolic function was related to the reduced collagen content, in
      particular in the highly cross-linked collagen type I, mainly in the peri-infarct
      region, although not via TGF-beta1 pathway. Our data indicate that PM treatment
      prevents the increase in AGEs levels and reduces collagen levels in a rat model
      of MI, resulting in an improved cardiac phenotype. As such, therapies targeting
      formation of AGEs might be beneficial in the prevention and/or treatment of
      maladaptive remodeling following MI.

PMID- 29167581
TI  - Publisher Correction: Time dependent decomposition of ammonia borane for the
      controlled production of 2D hexagonal boron nitride.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29167582
TI  - Pyridoxine dipharmacophore derivatives as potent glucokinase activators for the
      treatment of type 2 diabetes mellitus.
AB  - Glucokinase is one of the promising targets for glucose-lowering agents, and the
      development of GK activators are now considered as one of the most promising
      strategies for the treatment of type 2 diabetes mellitus. In this work, a series
      of novel symmetric molecular constructs, in which two pyridoxine moieties are
      connected via sulfur-containing linkers, have been synthesized and tested in
      vitro for glucokinase activation potential. The enzyme activation rates by two
      most active compounds at 100 MUM (~150% and 130%) were comparable to that of the
      reference agent PF-04937319 (~154%). Both leading compounds demonstrated low
      cytotoxicity and excellent safety profile in acute toxicity experiment in rats
      after oral administration with LD50 exceeding 2000 mg/kg of body weight. Binding
      mode of the active compounds in comparison with the reference agent was studied
      using molecular docking. The leading compounds represent viable preclinical
      candidates for the treatment of type 2 diabetes mellitus, as well as a promising
      starting point for the design of structural analogs with improved activity.

PMID- 29167584
TI  - Performance Monitoring of Chilled-Water Distribution Systems Using HVAC-Cx.
AB  - In this research we develop, test, and demonstrate the newest extension of the
      software HVAC-Cx (NIST and CSTB 2014), an automated commissioning tool for
      detecting common mechanical faults and control errors in chilled-water
      distribution systems (loops). The commissioning process can improve occupant
      comfort, ensure the persistence of correct system operation, and reduce energy
      consumption. Automated tools support the process by decreasing the time and the
      skill level required to carry out necessary quality assurance measures, and as a
      result they enable more thorough testing of building heating, ventilating, and
      air-conditioning (HVAC) systems. This paper describes the algorithm, developed by
      National Institute of Standards and Technology (NIST), to analyze chilled-water
      loops and presents the results of a passive monitoring investigation using field
      data obtained from BACnet(r) (ASHRAE 2016) controllers and presents field
      validation of the findings. The tool was successful in detecting faults in system
      operation in its first field implementation supporting the investigation phase
      through performance monitoring. Its findings led to a full energy
      retrocommissioning of the field site.

PMID- 29167583
TI  - The influence of curvature on the properties of the plasma membrane. Insights
      from atomistic molecular dynamics simulations.
AB  - In this work we conduct a systematic analysis of the influence of curvature on
      various properties of a realistic model of mammalian plasma membrane with
      asymmetric lipid content of monolayers and a realistic concentration of
      cholesterol. In order to do this we developed new technique for simulating
      membranes with the global membrane curvature restricted to any desirable value
      while keeping free lateral diffusion of the lipids and without introducing
      artifacts or perturbing the membrane structure. We show that the thickness of the
      hydrophobic core of the concave monolayer decreases by approximately 1.3 A in
      comparison to that of the flat membrane, while the thickness of the convex
      monolayer does not change. The order parameter of the lipid tails decreases
      significantly in the certain layers of the curved membrane. The area per lipid
      increases in the convex monolayer and decreases in the concave monolayer. The
      cholesterol inclination angle decreases when the curvature of a particular
      monolayer changes from concave to convex. The amount of cholesterol in the minor
      fraction located between the membrane leaflets is zero in the membrane with
      positive curvature and increases to 1.7% in the flat membrane and to 2.5% in the
      membrane with negative curvature.

PMID- 29167585
TI  - Judgments of Monkey's (Macaca mulatta) Facial Expressions by Humans: Does Housing
      Condition "Affect" Countenance?
AB  - The ability to interpret facial expressions of others is one of the more
      important abilities possessed by humans. However, is it possible for humans to
      accurately interpret the facial expressions of another species of primate, namely
      rhesus monkeys (Macaca mulatta)? We investigated this possibility by taking
      digital photos of four rhesus monkeys housed either singly or socially and
      allowing thirty-one participants to judge these photographs as representing
      either a happy, sad, or neutral monkey. Results indicated that the photographs of
      monkeys that were socially housed were more likely to be rated as happy or
      neutral than were photographs of singly housed monkeys. We suggest that these
      results imply important parallels between the perception of human and nonhuman
      primate facial expressions as well as introduce a potential new method for
      assessing nonhuman primate well-being.

PMID- 29167586
TI  - Promoting Pluralism in Counselling: an Untapped Source of Relational Mapping as
      Therapeutic Process.
AB  - This paper discusses the merits of pluralism in practice. It argues for a wider
      recognition of creative and integrative approaches, such as those used in the
      field of children's geographies (involving places and spaces), as a way of
      unlocking practitioner potential and innovation. By re-thinking child and human
      development, viewing it as socially, culturally and philosophically bound,
      through the proposed concept of 'vectors of entanglements', the author seeks to
      demonstrate and encourage the application of hybrid approaches across multi
      disciplinary fields. Through the use of diagramming and mapping the
      interconnectedness of relationships across space and place, the therapeutic
      process is brought to life to encourage practitioners to explore the 'invisible'
      threads that constitute significant meanings to clients.

PMID- 29167587
TI  - Editorial.

PMID- 29167588
TI  - Editorial.

PMID- 29167589
TI  - How different are their experiences and outcomes? Comparing aged out and other
      child welfare involved youth.
AB  - This paper adds to the growing body of research examining the experiences of
      youth aging out of the child welfare system. Through a comparison of youth aging
      out with two other groups of child welfare-involved youth-those whose families
      received child welfare services but were never placed out of home and those who
      were in out-of-home placement but did not age out-it presents a profile of their
      care careers and other system involvement (e.g., mental health, justice system).
      Analyses indicate that young people aging out of care have experienced
      significant amounts of time in out-of-home placement, a great deal of placement
      instability, and high levels of other system involvement. In general, their
      involvement is more extensive than that of the two comparison groups. However,
      the justice system involvement of youth who experienced out-of-home placement but
      did not age out is just as high as that of youth who have aged out. This finding
      highlights the importance of devoting resources not only to youth aging out of
      care but also to similarly-aged young people with prior child welfare
      involvement.

PMID- 29167590
TI  - Dynamic Latent Trait Models with Mixed Hidden Markov Structure for Mixed
      Longitudinal Outcomes.
AB  - We propose a general Bayesian joint modeling approach to model mixed longitudinal
      outcomes from the exponential family for taking into account any differential
      misclassification that may exist among categorical outcomes. Under this
      framework, outcomes observed without measurement error are related to latent
      trait variables through generalized linear mixed effect models. The misclassified
      outcomes are related to the latent class variables, which represent unobserved
      real states, using mixed hidden Markov models (MHMM). In addition to enabling the
      estimation of parameters in prevalence, transition and misclassification
      probabilities, MHMMs capture cluster level heterogeneity. A transition modeling
      structure allows the latent trait and latent class variables to depend on
      observed predictors at the same time period and also on latent trait and latent
      class variables at previous time periods for each individual. Simulation studies
      are conducted to make comparisons with traditional models in order to illustrate
      the gains from the proposed approach. The new approach is applied to data from
      the Southern California Children Health Study (CHS) to jointly model
      questionnaire based asthma state and multiple lung function measurements in order
      to gain better insight about the underlying biological mechanism that governs the
      inter-relationship between asthma state and lung function development.

PMID- 29167591
TI  - Identifying HIV Associated Neurocognitive Disorder Using Large-Scale Granger
      Causality Analysis on Resting-State Functional MRI.
AB  - We investigate the applicability of large-scale Granger Causality (lsGC) for
      extracting a measure of multivariate information flow between pairs of regional
      brain activities from resting-state functional MRI (fMRI) and test the
      effectiveness of these measures for predicting a disease state. Such pairwise
      multivariate measures of interaction provide high-dimensional representations of
      connectivity profiles for each subject and are used in a machine learning task to
      distinguish between healthy controls and individuals presenting with symptoms of
      HIV Associated Neurocognitive Disorder (HAND). Cognitive impairment in several
      domains can occur as a result of HIV infection of the central nervous system. The
      current paradigm for assessing such impairment is through neuropsychological
      testing. With fMRI data analysis, we aim at non-invasively capturing differences
      in brain connectivity patterns between healthy subjects and subjects presenting
      with symptoms of HAND. To classify the extracted interaction patterns among brain
      regions, we use a prototype-based learning algorithm called Generalized Matrix
      Learning Vector Quantization (GMLVQ). Our approach to characterize connectivity
      using lsGC followed by GMLVQ for subsequent classification yields good prediction
      results with an accuracy of 87% and an area under the ROC curve (AUC) of up to
      0.90. We obtain a statistically significant improvement (p<0.01) over a
      conventional Granger causality approach (accuracy = 0.76, AUC = 0.74). High
      accuracy and AUC values using our multivariate method to connectivity analysis
      suggests that our approach is able to better capture changes in interaction
      patterns between different brain regions when compared to conventional Granger
      causality analysis known from the literature.

PMID- 29167592
TI  - Using Large-Scale Granger Causality to Study Changes in Brain Network Properties
      in the Clinically Isolated Syndrome (CIS) Stage of Multiple Sclerosis.
AB  - Clinically Isolated Syndrome (CIS) is often considered to be the first
      neurological episode associated with Multiple sclerosis (MS). At an early stage
      the inflammatory demyelination occurring in the CNS can manifest as a change in
      neuronal metabolism, with multiple asymptomatic white matter lesions detected in
      clinical MRI. Such damage may induce topological changes of brain networks, which
      can be captured by advanced functional MRI (fMRI) analysis techniques. We test
      this hypothesis by capturing the effective relationships of 90 brain regions,
      defined in the Automated Anatomic Labeling (AAL) atlas, using a large-scale
      Granger Causality (lsGC) framework. The resulting networks are then characterized
      using graph-theoretic measures that quantify various network topology properties
      at a global as well as at a local level. We study for differences in these
      properties in network graphs obtained for 18 subjects (10 male and 8 female, 9
      with CIS and 9 healthy controls). Global network properties captured trending
      differences with modularity and clustering coefficient (p<0.1). Additionally,
      local network properties, such as local efficiency and the strength of
      connections, captured statistically significant (p<0.01) differences in some
      regions of the inferior frontal and parietal lobe. We conclude that multivariate
      analysis of fMRI time-series can reveal interesting information about changes
      occurring in the brain in early stages of MS.

PMID- 29167593
TI  - ESTABLISHING BRDF CALIBRATION CAPABILITIES THROUGH SHORTWAVE INFRARED.
AB  - Satellite instruments operating in the reflective solar wavelength region require
      accurate and precise determination of the Bidirectional Reflectance Distribution
      Functions (BRDFs) of the laboratory and flight diffusers used in their pre-flight
      and on-orbit calibrations. This paper advances that initial work and presents a
      comparison of spectral Bidirectional Reflectance Distribution Function (BRDF) and
      Directional Hemispherical Reflectance (DHR) of Spectralon, a common material for
      laboratory and on-orbit flight diffusers. A new measurement setup for BRDF
      measurements from 900 nm to 2500 nm located at NASA Goddard Space Flight Center
      (GSFC) is described. The GSFC setup employs an extended indium gallium arsenide
      detector, bandpass filters, and a supercontinuum light source. Comparisons of the
      GSFC BRDF measurements in the shortwave infrared (SWIR) with those made by the
      National Institute of Standards and Technology (NIST) Spectral Tri-function
      Automated Reference Reflectometer (STARR) are presented. The Spectralon sample
      used in this study was 2 inch diameter, 99% white pressed and sintered
      Polytetrafluoroethylene (PTFE) target. The NASA/NIST BRDF comparison measurements
      were made at an incident angle of 0 degrees  and viewing angle of 45 degrees .
      Additional BRDF data not compared to NIST were measured at additional incident
      and viewing angle geometries and are not presented here. The total combined
      uncertainty for the measurement of BRDF in the SWIR range made by the GSFC
      scatterometer is less than 1% (k = 1). This study is in support of the
      calibration of the Radiation Budget Instrument (RBI) and Visible Infrared Imaging
      Radiometer Suit (VIIRS) instruments of the Joint Polar Satellite System (JPSS)
      and other current and future NASA remote sensing missions operating across the
      reflected solar wavelength region.

PMID- 29167594
TI  - Ultrahigh-resolution multicolor colocalization of single fluorescent
      nanocrystals.
AB  - A new method for in vitro and possibly in vivo ultrahigh-resolution
      colocalization and distance measurement between biomolecules is described, based
      on semiconductor nanocrystal probes. This ruler bridges the gap between FRET and
      far-field (or near-field scanning optical microscope) imaging and has a dynamic
      range from few nanometers to tens of micrometers. The ruler is based on a stage
      scanning confocal microscope that allows the simultaneous excitation and
      localization of the excitation point-spread-function (PSF) of various colors
      nanocrystals while maintaining perfect registry between the channels. Fit of the
      observed diffraction and photophysics-limited images of the PSFs with a two
      dimensional Gaussian allows one to determine their position with nanometer
      accuracy. This new high-resolution tool opens new windows in various molecular,
      cell biology and biotechnology applications.

PMID- 29167595
TI  - Seasonal variations in C:N:Si:Ca:P:Mg:S:K:Fe relationships of seston from
      Norwegian coastal water: Impact of extreme offshore forcing during winter-spring
      2010.
AB  - The aim of this study was to reveal the relative content of C, N, Ca, Si, P, Mg,
      K, S and Fe in seston particles in Norwegian coastal water (NCW), and how it
      relates to biological and hydrographic processes during seasonal cycles from
      October 2009-March 2012. The following over all stoichiometric relationship for
      the time series was obtained: C66N11Si3.4Ca2.3P1Mg0.73S0.37K0.35Fe0.30, which is
      novel for marine waters. A record-breaking (187-year record) negative North
      Atlantic Oscillation (NAO) index caused extreme physical forcing on the Norwegian
      Coastal Current Water (NCCW) during the winter 2009-2010, and the inflow and
      upwelling of saline Atlantic water (AW) in the fjord was thus extraordinary
      during late spring-early summer in 2010. The element concentrations in fjord
      seston particles responded strongly to this convection, revealed by maximum
      values of all elements, except Fe, exceeding average values with 10.8 * for Ca,
      9.3 for K, 5.3 for S, 5.1 for Mg, 4.6 for Si, 4.0 for P, 3.8 for C, and 3.3 for N
      and Fe. This indicates that the signature of the Atlantic inflow was roughly two
      times stronger for Ca and K than for the others, probably connected with peaks in
      coccolithophorids and diatoms. There is, however, 1.5 * more of Si than Ca
      contained in the seston, which could be due to a stronger dominance of diatoms
      than coccolithophorids, confirming their environmental fitness. In total our data
      do not indicate any severe nutrient limitation with respect to N, P and Fe, but
      accumulation of iron by Fe-sequestering bacteria might at times reduce the
      availability of the dissolved Fe-fraction. There is a high correlation between
      most of the measured elements, except for Ca, which together with Fe only weakly
      correlated with the other elements. It is to be expected that environmental
      alterations in NCW related to climate change will influence the seston elemental
      composition, but the full effect of this will be strongly dependent on the future
      dominance of the high pressure versus low pressure systems (i.e. NAO index),
      since they are key regulators for the direction of wind driven vertical
      convection (i.e. upwelling or downwelling). Changes in stratification,
      temperature, light, pH (ocean acidification), CaCO3 concentrations (carbon pump)
      and availability of nutrients in the euphotic zone (biogeochemical cycling) are
      essential for the future dominance of coccolithophorids versus diatoms.

PMID- 29167596
TI  - Vocal foragers and silent crowds: context-dependent vocal variation in Northeast
      Atlantic long-finned pilot whales.
AB  - Abstract: Vocalisations form a key component of the social interactions and
      foraging behaviour of toothed whales. We investigated changes in calling and
      echolocation behaviour of long-finned pilot whales between foraging and non
      foraging periods, by combining acoustic recordings and diving depth data from
      tagged individuals with concurrent surface observations on social behaviour of
      their group. The pilot whales showed marked vocal variation, specific to foraging
      and social context. During periods of foraging, pilot whales showed more vocal
      activity than during non-foraging periods (rest, travel). In addition to the
      expected increase in echolocation activity, call rates also increased, suggesting
      that pilot whales communicate more during foraging. Furthermore, calls with
      multiple inflections occurred more often immediately before and after foraging
      dives and during the early descent and late ascent phases of foraging dives.
      However, these calls were almost never detected at diving depths of the tagged
      whale beyond 350 m. Calls with no or few inflections were produced at all times,
      irrespective of diving depth of the tagged whale. We discuss possible
      explanations for the distinct vocal variation associated with foraging periods.
      In addition, during non-foraging periods, the pilot whales were found to be more
      silent (no calling or echolocation) in larger, more closely spaced groups. This
      indicates that increased levels of social cohesion may release the need to stay
      in touch acoustically. Significance statement: Social toothed whales rely on
      vocalisations to find prey and interact with conspecifics. Species are often
      highly vocal and can have elaborate call repertoires. However, it often remains
      unclear how their repertoire use correlates to specific social and behavioural
      contexts, which is vital to understand toothed whale foraging strategies and
      sociality. Combining on-animal tag recordings of diving and acoustic behaviour
      with observations of social behaviour, we found that pilot whales produce more
      calls during foraging than during non-foraging periods. Moreover, highly
      inflected calls were closely associated to the periods around and during foraging
      dives. This indicates enhanced communication during foraging, which may, for
      example, enable relocation of conspecifics or sharing of information. Whales
      reduced their vocal activity (calling and echolocation) at increased levels of
      social cohesion, indicating that in certain behavioural contexts, closer
      association (i.e. more closely spaced) may release the need to stay in touch
      acoustically.

PMID- 29167597
TI  - Research on Adolescence in the Twenty-First Century.
AB  - Recent methodological advances have allowed empirical research on adolescence to
      do better justice to theoretical models. Organized by a life course framework,
      this review covers the state of contemporary research on adolescents' physical,
      psychological, interpersonal, and institutional pathways; how these pathways
      connect within primary ecological contexts; and how they relate to broader
      patterns of societal stratification and historical change. Looking forward, it
      also emphasizes three future challenges/opportunities, including efforts to
      illuminate biosocial processes, link adolescence to other life stages, and
      account for the influence of major social changes (e.g., the new media).

PMID- 29167598
TI  - The relationship between birch pollen, air pollution and weather types and their
      effect on antihistamine purchase in two Swedish cities.
AB  - Exposure to elevated air pollution levels can aggravate pollen allergy symptoms.
      The aim of this study was to investigate the relationships between airborne birch
      (Betula) pollen, urban air pollutants NO2, O3 and PM10 and their effects on
      antihistamine demand in Gothenburg and Malmo, Sweden, 2006-2012. Further, the
      influence of large-scale weather pattern on pollen-/pollution-related risk, using
      Lamb weather types (LWTs), was analysed. Daily LWTs were obtained by comparing
      the atmospheric pressure over a 16-point grid system over southern Sweden (scale
      ~3000 km). They include two non-directional types, cyclonic (C) and anticyclonic
      (A) and eight directional types depending on the wind direction (N, NE, E...).
      Birch pollen levels were exceptionally high under LWTs E and SE in both cities.
      Furthermore, LWTs with dry and moderately calm meteorological character (A, NE,
      E, SE) were associated with strongly elevated air pollution (NO2 and PM10) in
      Gothenburg. For most weather situations in both cities, simultaneously high birch
      pollen together with high air pollution had larger over-the-counter (OTC) sales
      of antihistamines than situations with high birch pollen alone. LWTs NE, E, SE
      and S had the highest OTC sales in both cities. In Gothenburg, the city with a
      higher load of both birch pollen and air pollution, the higher OTC sales were
      especially obvious and indicate an increased effect on allergic symptoms from air
      pollution. Furthermore, Gothenburg LWTs A, NE, E and SE were associated with high
      pollen and air pollution levels and thus classified as high-risk weather types.
      In Malmo, corresponding high-risk LWTs were NE, E, SE and S. Furthermore,
      occurrence of high pollen and air pollutants as well as OTC sales correlated
      strongly with vapour pressure deficit and temperature in Gothenburg (much less so
      in Malmo). This provides evidence that the combination of meteorological
      properties associated with LWTs can explain high levels of birch pollen and air
      pollution. Our study shows that LWTs represent a useful tool for integrated daily
      air quality forecasting/warning.

PMID- 29167599
TI  - Inhalable dust, endotoxins and (1-3)-beta-d-glucans as indicators of exposure in
      waste sorting plant environment.
AB  - The aim of the study was to assess the levels of inhalable dust, endotoxins and
      (1-3)-beta-d-glucans as agents harmful to the respiratory tract of workers of
      municipal waste sorting plants and interaction between these agents based on the
      measurements taken in two plants with different processing capacities. The study
      was conducted in summer season in two waste sorting plants (WSPs) differing in
      processing capacity. Samples of bioaerosol for inhalable dust (gravimetric
      method), endotoxins (LAL test in kinetic, chromogenic version) and (1-3)-beta-d
      glucans (Glucatell test in kinetic version) were collected from 42 sorting
      workers using individual aspirators with glass fiber filters during the work
      shift. Average geometric concentrations (geometric standard deviation; min-max)
      of inhalable dust, endotoxins and (1-3)-beta-d-glucans were: WSP1: 1.7 mg m-3
      (2.2; 0.6-6.9 mg m-3); 15.9 ng m-3 (2.1; 5.4-78.9 ng m-3), 55.1 ng m-3 (1.8; 20.7
      188.6 ng m-3) and WSP2: 0.8 mg m-3 (2.2; 0.2-3.8 mg m-3), 9.8 ng m-3 (2.4; 1.6
      29.7 ng m-3), 45.0 ng m-3 (3.2, 5.7-212.9 ng m-3), respectively. A significantly
      higher concentration of inhalable dust was recorded in WSP1 with bigger
      processing capacity compared to WSP2 (less processing capacity). Significant (p <
      0.05) and very high correlations (Spearman rank R > 0.7) were found between the
      concentrations of all analyzed harmful agents. Processing capacity of waste
      sorting plants differentially affects the concentrations of inhalable dust,
      whereas concentrations of endotoxins and glucans are less clearly affected. This
      suggests that relative concentrations of endotoxin and glucan are depending on
      the waste sorting capacity.

PMID- 29167600
TI  - Allergenic Asteraceae in air particulate matter: quantitative DNA analysis of
      mugwort and ragweed.
AB  - Mugwort (Artemisia vulgaris) and ragweed (Ambrosia artemisiifolia) are highly
      allergenic Asteraceae. They often cause pollen allergies in late summer and fall.
      While mugwort is native to Europe, ragweed reached Europe as a neophyte from
      North America about 150 years ago and continued spreading ever since. To
      understand possible relationships between the spread of ragweed, its abundance in
      air, and to judge possible health risks for the public, we quantified ragweed DNA
      in inhalable fine as well as in coarse air particulate matter. Mugwort was chosen
      for comparison, as it is closely related to ragweed and grows in similar, though
      mainly not identical, habitats but is native to Germany. The DNA quantification
      was performed on atmospheric aerosol samples collected over a period of 5 years
      in central Europe. The DNA concentrations were highest during the characteristic
      pollination periods but varied greatly between different years. In the inhalable
      fine particle fraction, ragweed exceeds the mugwort DNA concentration fivefold,
      while the coarse particle fraction, bearing intact pollen grains, contains more
      mugwort than ragweed DNA. The higher allergenic potential of ragweed might be
      linked to the humidity or long-range transport-induced bursting of ragweed pollen
      into smaller allergenic particles, which may reach the lower airways and cause
      more intense allergic reactions. Airborne ragweed DNA was detected also outside
      the local pollination periods, which can be explained by atmospheric long-range
      transport. Back-trajectory analyses indicate that the air masses containing
      ragweed DNA during winter had originated in regions with milder climate and large
      ragweed populations (Southern France, Carpathian Basin).

PMID- 29167601
TI  - Tectonic evolution and paleokarstification of carbonate rocks in the Paleozoic
      Tarim Basin.
AB  - Thick carbonate rocks were developed in the depression of the Tarim craton during
      the Cambrian-Middle Ordovician periods. The compressional tectonic movement
      during the Middle Caledonian-Hercynian created the paleouplifts, which became the
      base for the paleokarst in the Ordovician carbonate rocks. Based on the large
      quantity of seismic, drilling, and geological outcrop data, this study analyzed
      the paleokarst development in relation to the multi-stage tectonic movements in
      the Paleozoic Era and different stages of karstification and hypothesized
      paleogeomorphology and paleokarst water system of those stages. Fractures from
      the tectonic movements in the carbonate and non-carbonate rocks were essential
      for water cycle, and therefore, the karst development in deep carbonate rocks.
      Paleokarsts in the Tarim Basin can be classified into four major types based on
      the paleogeomorphology, degree of karstification, and the layering, i.e., Tahe
      type, gentle hill type, high steep hill type, and covered-semi-open type.
      Relatively, the Tahe type was mostly on hill slopes and had the strongest
      karstification, the gentle hill type often located in the plain areas or basin
      bottoms and had least karstification, the high steep hill type was controlled by
      faults and had medium karstification, the semi-open type was controlled by
      precipitation and hydraulic gradient, and fracture passages and karst caves were
      mostly developed along major fractures. Overall, the paleokarsts of the
      Ordovician carbonate rocks in the Tarim Basin can be characterized by long
      geologic history, multiple development stages, deep burial depth, and various
      karst types.

PMID- 29167602
TI  - Rapid, Reversible Release from Thermosensitive Liposomes Triggered by Near-Infra
      Red Light.
AB  - We present a novel drug carrier consisting of plasmonic hollow gold nanoshells
      (HGN) chemically tethered to liposomes made temperature sensitive with lysolipids
      (LTSL). Continuous-wave irradiation by physiologically friendly near infra-red
      light at 800 nm for 2.5 minutes at laser intensities an order of magnitude below
      that known to damage skin generates heating localized to the liposome membrane.
      The heating increases the liposome permeability in an irradiation dose-dependent,
      but reversible manner, resulting in rapid release of small molecules such as the
      self-quenching dye carboxyfluorescein or the chemotherapeutic doxorubicin,
      without raising the bulk temperature. The local rise in nanoshell temperature
      under laser irradiation was inferred by comparing dye release rates from the LTSL
      via bulk heating to that induced by irradiation. Laser-irradiation of LTSL
      enables precise control of contents release with low temperature gradients
      confined to areas irradiated by the laser focus. The combined effects of rapid
      local release and localized hyperthermia provide a synergistic effect as shown by
      a near doubling of androgen resistant PPC-1 prostate cancer cell toxicity
      compared to the same concentration of free doxorubicin.

PMID- 29167603
TI  - On-demand generation and mixing of liquid-in-gas slugs with digitally
      programmable composition and size.
AB  - Microscopic droplets or slugs of mixed reagents provide a convenient platform for
      performing large numbers of isolated biochemical or chemical reactions for many
      screening and optimization applications. Myriad microfluidic approaches have
      emerged for creating droplets or slugs with controllable size and composition,
      generally using an immiscible carrier fluid to assist with the formation or
      merging processes. We report a novel device for generation of liquid slugs in air
      when the use of a carrier liquid is not compatible with the application. The slug
      generator contains two adjacent chambers, each of which has a volume that can be
      digitally adjusted by closing selected microvalves. Reagents are filled into the
      two chambers, merged together into a contiguous liquid slug, ejected at the
      desired time from the device using gas pressure, and mixed by flowing in a
      downstream channel. Programmable size and composition of slugs is achieved by
      dynamically adjusting the volume of each chamber prior to filling. Slug formation
      in this fashion is independent of fluid properties and can easily be scaled to
      mix larger numbers of reagents. This device has already been used to screen
      monomer ratios in supramolecular nanoparticle assembly and radiolabeling
      conditions of engineered antibodies, and here we provide a detailed description
      of the underlying device.

PMID- 29167604
TI  - Lumbar facet joint injection in treating low back pain: Radiofrequency
      denervation versus SHAM procedure. Systematic review.
AB  - The lumbar facet joints have been implicated as one of the causes of low-back
      pain syndromes. About 15-40% of patients who presented with chronic low-back pain
      was attributed to lumbar facet joint pain. The purpose of this study was to
      analyse whether radiofrequency denervation is better than SHAM procedure in
      treating chronic low-back pain caused by lumbar zygapophysial joints pathology.
      From the four identified randomised control trials, there is conflicting evidence
      at an intermediate 3-6-month stage, however; one study demonstrates statistical
      significance of radiofrequency denervation at 3 months. Longer-term follow-up is
      needed to prove the efficacy of radiofrequency denervation technique.

PMID- 29167605
TI  - Clinical outcomes involving patients that develop septic arthritis with
      methicillin sensitive staphylococcus aureus versus methicillin resistant
      staphylococcus aureus.
AB  - Septic Arthritis is an orthopedic emergency that requires prompt diagnosis and
      treatment. Staphylococcus aureus is the most common pathogen causing septic
      arthritis. This review seeks to describe clinical characteristics and outcomes
      associated with patients with methicillin-resistant (MRSA) vs. methicillin
      sensitive staphylococcus aureus (MSSA) septic arthritis. The review showed that
      those infected with MRSA were older, had more chronic medical conditions, and
      higher values of inflammatory markers. MRSA septic arthritis was also associated
      with more complications, longer duration of antibiotics, and increased mortality.
      Thus, health care providers should maintain a high index of suspicion, diagnose,
      and treat aggressively to prevent adverse outcomes.

PMID- 29167606
TI  - Results of operative 4-in-1 patella realignment in children with recurrent
      patella instability.
AB  - Purpose: Recurrent patellar instability is a cause of knee dysfunction,
      limitation and pain for children. If nonoperative treatment fails to stabilise
      the patella, operative realignment and stabilisation have been advocated.
      Operative techniques in the paediatric population must preserve physeal growth
      while ensuring stability. We aimed to determine the outcome of children and
      adolescents who underwent a 4-in-1 patellar realignment (lateral release, medial
      reefing, Insall tube realignment and Roux-Goldthwaite patella ligament transfer).
      Methods: Consecutive skeletally immature patients operated in our institution
      were included in the study. A total of 16 operated knees in 12 patients were
      recruited. All patients underwent the same procedure after attempting a minimum
      period of 6 months of non-operative treatment with unsatisfactory results. The
      main outcome measured was recurrent dislocations. Functional outcomes were
      assessed using the Kujala score and the Paediatric form of the International Knee
      Documentation Committee Subjective Knee Form (Pedi-IKDC). Results: Patients were
      followed up for a minimum of 3 years. None of the patients sustained further
      patella dislocations following the operation. In 3 cases, minor patellar
      maltracking was noted post-operatively but all 3 remained asymptomatic. Three
      patients had a small area of numbness lateral to the operative incision, which
      coincided with hypertrophic scarring. There was one case of superficial wound
      infection. The mean Kujala score was 83.4 +/- 11.47 and the mean Pedi-IKDC was
      79.5 +/- 12.56 at the latest follow-up (minimum of 36 months). Conclusions: The 4
      in-1 patellar realignment is a good procedure in paediatric and adolescent
      patients with recurrent patella instability. Satisfactory results were observed
      with a minimal complication and redislocation rate in our series.

PMID- 29167607
TI  - Impact of Intra-Aortic Balloon Counterpulsation on Prognosis of Patients with
      Acute Myocardial Infarction: A Meta-Analysis.
AB  - Background: This study aimed to evaluate the impact of intra-aortic balloon
      counterpulsation (IABP) on the prognosis of patients with acute myocardial
      infarction (AMI). Methods: We identified and included in this study AMI cases
      treated with IABP from January 1970 to May 2014. For statistical analysis, we
      utilized RevMan 5.0 software. Results: Fourteen RCTs with a total population of
      2538 were included in this study. The in-hospital and 30-day mortality rate in
      the IABP group was not significantly lower than those in the non-IABP group.
      Subgroup analysis according to the type of revascularization, OR values of TT
      subgroup, PCI subgroup, and CABG subgroup were 0.64 (95% CI 0.25-1.61, p = 0.34),
      0.85 (95% CI 0.65-1.11, p = 0.23) and 0.46 (95% CI 0.13-1.63, p = 0.23). And OR
      values of AMI patients in the before and after PCI subgroup were 0.43 (95% CI
      0.21-0.91, p = 0.03) and 1.36 (95% CI 0.76-2.41, p = 0.30). The 6-month mortality
      in the IABP group was not significantly lower than that in the non-IABP group.
      And OR values of 6-month mortalities of the before and after PCI subgroup were
      0.47 (95% CI 0.26-0.86, p = 0.01) and 1.40 (95% CI 0.57-3.45, p = 0.47).
      Conclusions: IABP did not reduce the in-hospital and 30-day mortality of AMI
      patients, and did not reduce the 6-month mortality. But IABP used in AMI patients
      before PCI was associated not only with reduced in-hospital and 30-day mortality,
      but also reduced 6-month mortality.

PMID- 29167608
TI  - Initiation of Intra-Aortic Balloon Counterpulsation before Percutaneous Coronary
      Intervention in Patients with Acute Myocardial Infarction and High-Risk Features
      Might be Beneficial: Questions Remain.

PMID- 29167609
TI  - The Application and Future of Big Database Studies in Cardiology: A Single-Center
      Experience.
AB  - As medical research techniques and quality have improved, it is apparent that
      cardiovascular problems could be better resolved by more strict experiment
      design. In fact, substantial time and resources should be expended to fulfill the
      requirements of high quality studies. Many worthy ideas and hypotheses were
      unable to be verified or proven due to ethical or economic limitations. In recent
      years, new and various applications and uses of databases have received
      increasing attention. Important information regarding certain issues such as rare
      cardiovascular diseases, women's heart health, post-marketing analysis of
      different medications, or a combination of clinical and regional cardiac features
      could be obtained by the use of rigorous statistical methods. However, there are
      limitations that exist among all databases. One of the key essentials to creating
      and correctly addressing this research is through reliable processes of analyzing
      and interpreting these cardiologic databases.

PMID- 29167610
TI  - The Difference on Features of Fragmented QRS Complex and Influences on Mortality
      in Patients with Acute Coronary Syndrome.
AB  - Objectives: To investigate whether the fragmented QRS (fQRS) complexes can be
      used to distinguish patients with early non-ST elevation myocardial infarction
      (NSTEMI) from those with unstable angina (UA). Background: fQRS complex has been
      found to be linked to myocardial infarction and cardiac death. Methods: The
      clinical data of 302 patients who had been diagnosed with coronary artery disease
      were retrospectively reviewed. Incidence of fQRS complex within 48 h of
      presentation was analyzed and patients with acute myocardial infarction (AMI) (n
      = 240) were followed up by telephone interviews for a mean of 61.47 (range, 59.60
      63.35) months. Results: Patients with NSTEMI exhibited higher incidence of fQRS
      than those with UA (p = 0.047). The incidence of fQRS in the inferior wall leads
      was significantly higher than that of other leads in patients with anterior wall
      infarction (p < 0.05). Kaplan-Meier analysis revealed a higher mortality rate in
      AMI patients with fQRS compared to non-fQRS patients (p = 0.001). Conclusions:
      Presence of fQRS complexes within 48 hours of presentation may be used to
      differentiate NSTEMI patients from UA patients. fQRS may also be used as a
      survival predictor for patients with AMI.

PMID- 29167611
TI  - Usefulness of Fragmented QRS Complex for Diagnosis and Outcome Prediction in
      Patients with Coronary Artery Disease.

PMID- 29167612
TI  - The Value of CHA2DS2VASC Score in Predicting All-Cause Mortality in Patients with
      ST-Segment Elevation Myocardial Infarction Who Have Undergone Primary
      Percutaneous Coronary Intervention.
AB  - Background: Acute coronary syndrome is the most common cause of cardiac morbidity
      and death. Various scoring systems have been developed in order to identify
      patients who are at risk for adverse outcome and may benefit from more aggressive
      and effective therapies. Objectives: This study was designed to evaluate the
      CHA2DS2VASC score as a predictor of mortality inpatients with ST-elevation
      myocardial infarction undergoing primary percutaneous coronary intervention (p
      PCI). Methods: We evaluated 300 patients diagnosed with ST-elevation myocardial
      infarction who underwent p-PCI and calculated their CHA2DS2VASC scores. According
      to their CHA2DS2VASC scores, patients were divided into three groups. Group 1: 0
      1 points (n = 101), Group 2: 2-3 points (n = 129), and Group 3: 4-9 points (n =
      70). The mean, median and minimum duration of follow-up were 21.7 +/- 9.4, 21,
      and 12 months, respectively. All-cause mortality was defined as the primary
      endpoint of the study. Results: All-cause mortality was 4% in Group 1, 8.5% in
      Group 2 and 27.1% in Group 3 respectively. Kaplan-Meier analysis showed that
      Group 3 (CHA2DS2VASC >= 4) had a significantly higher incidence of death [p (log
      rank) < 0.001]. In ROC analysis, AUC values for in hospital, 12-month and long
      term mortality were 0.88 (0.77-0.99 95% CI), 0.82 (0.73-0.92 95% CI) and 0.79
      (0.69-0.88 95% CI), respectively. Conclusions: CHA2DS2VASC score can be used for
      predicting both in-hospital, 12-month and long-term mortality in patients with
      STEMI who have undergone p-PCI.

PMID- 29167613
TI  - Clinical Outcomes of Polytetrafluoroethylene-Covered Stents for Coronary Artery
      Perforation in Elderly Patients Undergoing Percutaneous Coronary Interventions.
AB  - Background: Coronary artery perforation (CAP) during percutaneous coronary
      intervention (PCI) is associated with increased mortality.
      Polytetrafluoroethylene covered stents (CS) are an effective approach to treat
      CAP, but data regarding elderly patients requiring CS implantation for CAP are
      limited. The aim of this study is to report clinical data for elderly CAP
      patients undergoing CS implantation during PCI. Methods: Nineteen consecutive
      elderly patients (>= 65 years) undergoing CS implantation due to PCI-induced CAP
      in a tertiary referral center from July 2003 to April 2016 were retrospectively
      examined. Results: There were 13 men and six women, with a mean age of 75.3 +/-
      5.6 years (range: 65-86 years). Perforation grade was Ellis type II in five
      patients (26.3%), and Ellis type III in 14 patients (73.7%). Cardiac tamponade
      developed in six patients (31.6%), and intra-aortic balloon pumping was needed in
      four patients (21.1%). The overall success rate for CS implantation rate was
      94.7%. The overall in-hospital mortality rate was 15.8%; the in-hospital
      myocardial infarction rate was 63.2%. Among 16 survival-to-discharge cases, dual
      antiplatelet therapy (DAPT) was prescribed in 14 cases (87.5%) for a mean
      duration of 14 months. Overall, there were five angiogram- proven CS failures
      among 18 patients receiving successful CS implantation. The 1, 2 and 4 years of
      actuarial freedom from the CS failure were 78%, 65%, and 43% in the angiogram
      follow-up patients. Conclusions: CS implantation for CAP is feasible and
      effective in elderly patients, while CS failure remains a major concern that
      encourages regular angiographic follow-up in these case.

PMID- 29167614
TI  - Thirty-Day and One-Year Clinical Outcomes of Bioresorbable Vascular Scaffold
      Implantation: A Single-Center Experience.
AB  - Background: Available data on the use of the Bioresorbable vascular scaffold
      (BVS) (Abbott Vascular, Santa Clara, CA) in real-world patients is limited,
      particularly in Asian populations. The aim of this study was to assess clinical
      outcomes of patients treated with a BVS in real-world practice in Taiwan.
      Methods: This study focused on 156 patients with coronary artery disease and a
      total of 249 lesions who received BVS implantation from October 2012 to October
      2015. The study's primary endpoint was major adverse cardiac event (MACE), such
      as a myocardial infarction (MI), target vessel revascularization (TVR), target
      lesion revascularization (TLR), definite or possible scaffold thrombosis,
      cardiovascular death, and all-cause mortality during the thirty-day follow-up
      period. The secondary endpoint was MACE during the one-year follow-up period.
      Additionally, the composite clinical secondary endpoint was target lesion failure
      (TLF), which was called device-oriented composite endpoint. Results: The average
      age of the patients was 60.34 +/- 10.15 years, and 81.4% were male. The average
      of Syntax score was 12.42 +/- 8.77 points. 44.2 % lesions were type B2 or C. At
      31 days, one patient experienced a MACE (1/156) the composite of two TLF (2/249)
      with ST elevation MI, which was related to scaffold thrombosis. At one-year, 5.1
      % (8/156) of the patients experienced a MACE and 3.6% (9/249) of the lesions
      experienced a TLF. There was no cardiovascular or all-cause mortality in the 30
      day follow-up. The one-year cardiovascular and all-cause mortality rates were
      each 1.3%, respectively. Diabetes, ostial lesion, bifurcation lesion, and non
      standard dual anti-platelet therapy (DAPT) were the strong associations of one
      year TLF. Conclusions: Even with difficult and complex lesions of patients in
      this study, acceptable outcomes were achieved with low definite or possible
      scaffold thrombosis rates after BVS implantation. And despite anatomical issues,
      it is important to complete standard DAPT.

PMID- 29167615
TI  - Vocal Cord Paralysis and Laryngeal Trauma in Cardiac Surgery.
AB  - Background: Cardiac surgery - associated iatrogenic laryngeal trauma is often
      overlooked. We investigated the risk factors of vocal cord paralysis in cardiac
      surgery. Methods: Medical records were reviewed from 169 patients who underwent
      elective or emergency cardiac surgeries. Patients had transesophageal
      echocardiography (TEE) placed either under video fiberscopic image guidance
      (guided group) or blind placement (blind group). Routine postoperative
      otolaryngologist consultation with video laryngoscopic recording were performed.
      Results: Vocal cord paralyses were found in 18 patients (10.7%; left-13, right-4,
      bilateral-1). The risk of vocal cord paralysis was associated with emergency
      operation [odds ratio, 97.5 (95% confidence interval [CI], 2.9 to 366), p =
      0.01]. Use of fiberscope-guided TEE [odds ratio, 0.04 (95% CI 0.01 to 0.87), p =
      0.04] can effectively reduce vocal cord injury. Conclusions: Emergency cardiac
      surgery increased the risk of vocal cord paralysis. Fiberscope-guided TEE
      placement is recommended for all patients having cardiac surgery to decrease the
      risk of severe peri-operative laryngeal trauma.

PMID- 29167616
TI  - Surgical Acute Volume-Overload Impacts Early on Myocardium - An Experimental
      Study.
AB  - Background: Acute volume-overload (AVO) predisposes to cardiac failure. Global
      cardiac injury may ensue after acute right-sided distension of the heart due to
      AVO. We experimentally investigated whether surgical AVO impacts early on the
      myocardium and some markers of injury. Methods: Thirty-four syngeneic Fisher rats
      underwent surgical abdominal aortocaval fistula to induce AVO. The hearts were
      procured for regional and quantitative histology after one and three days. Gene
      expressions for atrial natriuretic peptide (ANP), matrix metalloprotease 9
      (MMP9), transforming growth factor beta (TGFbeta) and YKL40 were investigated for
      myocardial injury. Results: The relative number of ischemic intramyocardial
      arteries were abundant in the septum of the hearts with AVO compared with
      controls at day 1 and 3 [0.16 +/- 0.02 vs. 0.02 +/- 0.01, point score unit (PSU),
      p = 0.002 and 0.14 +/- 0.02 vs. 0.02 +/- 0.01, PSU, p = 0.009, respectively]
      followed by similar changes in the left ventricle at day 3 (0.11 +/- 0.02 vs.
      0.04 +/- 0.01, PSU, p = 0.007). Indicating early myocardial injury, ANP (p =
      0.019) was increased in AVO hearts as compared with controls at day 1, as
      expected. More interestingly, MMP9 (p = 0.003 and p = 0.006), TGFbeta (p = 0.002
      and p = 0.004) and YKL40 (p = 0.001 and p = 0.003) expressions were significantly
      increased at day 1 and 3, along with macrophage infiltration into the myocardium
      supporting the role of factors produced by alternatively activated macrophages in
      the pathogenesis of AVO-induced pathophysiology in the heart. Conclusions:
      Surgical AVO induces an early ischemic myocardial response observed in the
      intramyocardial arteries. Early expression of key parameters of cardiac
      remodeling suggest for the onset of early cardiac failure after AVO.

PMID- 29167617
TI  - Statin Attenuated Myocardial Inflammation Induced by PM2.5 in Rats.
AB  - Background: Here, the study aims to explore the effect of PM2.5 exposure on
      atherosclerosis in rats. Materials and Methods: 32 Wistar rats were selected in
      our study. An atherosclerosis model was established. All rats were evenly divided
      into four groups, including normal control group (NC), model control group (MC),
      model PM2.5 group (PM2.5) and model Atorvastatin group (Atorvastatin). The rats
      in NC and model control group were treated with saline 1 ml/kg body weight by
      tail intravenous injection, while the rats in PM2.5 group were exposed to PM2.5
      suspension. The rats in atorvastatin group were given atorvastatin by gavage with
      10 mg.kg-1.per day for 12 weeks until PM2.5 injection. After 24 h, all rats in
      each group were sacrificed. Pathological analysis, immunohistochemistry (IHC) and
      electrophoretic mobility shift assays (EMSA) were carried out. Results: PM2.5
      exposure significantly reduced the levels of triglyceride (TG), high density
      lipoprotein (HDL) and superoxide dismutase (SOD), but promoted the levels of
      total cholesterol (TC), low density lipoprotein (LDL), atherosclerosis index
      (AI), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha) and high
      sensitivity C-reactive protein (hs-CRP) in the rats of PM2.5 group than MC group
      (p < 0.05). PM2.5 group showed activated nuclear factor-kappa B (NF-kappaB),
      seriously damaged myocardial coronary branches and the highest nuclear
      translocation rate. Atorvastatin significantly improved the levels of TG, HDL,
      SOD, interleukin-6 (IL-6), and reduced the levels of TC, LDL, AI, MDA, TNF-alpha,
      hs-CRP, oxidized low-density lipoprotein (ox-LDL) and blood pressure, even the
      nuclear translocation rate. Conclusions: PM2.5 exposure contributes to
      atherosclerosis in rats, which correlate with the levels of cholesterol,
      oxidative stress and inflammatory response. Atorvastatin could attenuate
      myocardial inflammation caused by PM2.5 exposure in rats.

PMID- 29167618
TI  - Air Pollution Particular Matter and Atherosclerosis.

PMID- 29167619
TI  - Exenatide Inhibits the KCa3.1 Channels of Aortic Vascular Smooth Muscle in
      Diabetic Rats.
AB  - Background: KCa3.1 ion channels play an important role during atherosclerosis. We
      aimed to investigate the effect of exenatide on KCa3.1 expression in aortic
      vascular smooth muscle cells (VSMCs) of diabetic rats. Methods: Sprague-Dawley
      rats were randomly divided into normal control (NC), diabetes model (DM), and
      exenatide treatment (ET) groups. Hematoxylin and eosin and alpha-actin
      immunohistochemical staining were used to detect changes in rat aortic vascular
      smooth muscle. Quantitative RT-PCR and Western blot analysis were used to detect
      changes in KCa3.1 mRNA and protein levels, respectively. Results: Aortic tissue
      staining in the DM group revealed an absence of smooth or integrated endothelium,
      increased smooth muscle cell proliferation in the media, smooth muscle
      hyperplasia, disorganized smooth muscle cells, and an increased number of
      collagen fibers, relative to the NC and ET groups. KCa3.1 mRNA expression was
      higher in the DM group than in the NC and ET groups. Similarly, the KCa3.1
      protein level was higher in the DM group than in the NC and ET groups. The KCa3.1
      protein level did not significantly differ between the ET and NC groups.
      Conclusions: Exenatide could inhibit the expression of the KCa3.1 channel in
      VSMCs of diabetic rats.

PMID- 29167620
TI  - Obstructive Sleep Apnea Independently Increases the Incidence of Heart Failure
      and Major Adverse Cardiac Events: A Retrospective Population-Based Follow-Up
      Study.
AB  - Background: Obstructive sleep apnea (OSA) is common in heart failure (HF)
      patients and exacerbates the outcome of this chronic disease. However, the
      frequency of HF arising from OSA is varied, with little supporting literature.
      Here, we aimed to clarify the incidence risk of HF and major adverse cardiac
      events (MACEs) in OSA patients from the Taiwan large database. Methods and
      Results: From 2000-2010, a total of 2699 newly diagnosed OSA patients after
      polysomnographic study and 13,490 non-OSA patients utilizing 1:5 matching was
      enrolled and followed to 2011. Compared to the non-OSA cohort, the OSA cohort
      increased its MACEs incidence 1.95-fold high and HF incidence reached its highest
      level, up to 2.75-fold [confidential interval (CI): 1.76-4.29; p value < 0.001].
      The most common MACE event was stroke, with a 1.75-fold higher risk in the OSA
      cohort (CI: 1.37-2.20; p value < 0.001). Although the trend is similar, the OSA
      cohort showed an increased incidence of atrial fibrillation of approximately 1.63
      fold high, (CI: 0.78-3.40; p value: 0.193) and 1.44 high, (CI: 0.74-2.79; p
      value: 0.287) in myocardial infarction. Between genders, HF risk is considerably
      higher in female OSA cohort than in corresponding males [female: 6.13 (2.68
      14.00), p value < 0.01; male: 1.95 (1.11-3.43), p value = 0.020]. Conclusions:
      OSA patients have nearly triple the HF incidence risk than the non-OSA
      population, particularly in female OSA patients.

PMID- 29167621
TI  - Is a Three-Dimensional Printing Model Better Than a Traditional Cardiac Model for
      Medical Education? A Pilot Randomized Controlled Study.
AB  - Background: Three-dimensional (3D) printing is a newly-emerged technology
      converting a series of two-dimensional images to a touchable 3D model, but no
      studies have investigated whether or not a 3D printing model is better than a
      traditional cardiac model for medical education. Methods: A 3D printing cardiac
      model was generated using multi-slice computed tomography datasets. Thirty-four
      medical students were randomized to either the 3D Printing Group taught with the
      aid of a 3D printing cardiac model or the Traditional Model Group with a commonly
      used plastic cardiac model. Questionnaires with 10 medical questions and 3
      evaluative questions were filled in by the students. Results: A 3D printing
      cardiac model was successfully generated. Students in the 3D Printing Group were
      slightly quicker to answer all questions when compared with the Traditional Model
      Group (224.53 +/- 44.13 s vs. 238.71 +/- 68.46 s, p = 0.09), but the total score
      was not significantly different (6.24 +/- 1.30 vs. 7.18 +/- 1.70, p = 0.12).
      Neither the students'satisfaction (p = 0.48) nor their understanding of cardiac
      structures (p = 0.24) was significantly different between two groups. More
      students in the 3D Printing Group believed that they had understood at least 90%
      of teaching content (6 vs. 1). Both groups had 12 (70.6%) students who preferred
      a 3D printing model for medical education. Conclusions: A 3D printing model was
      not significantly superior to a traditional model in teaching cardiac diseases in
      our pilot randomized controlled study, yet more studies may be conducted to
      validate the real effect of 3D printing on medical education.

PMID- 29167622
TI  - Is a Three-Dimensional Printed Cardiac Model Better Than a Traditional Cardiac
      Model for Medical Education?

PMID- 29167623
TI  - Bioresorbable Vascular Scaffold Stent Delivered to Tortuous Lesions by Using the
      "Five-in-Six" System.
AB  - A 5Fr ST01, which is a straight-tip guiding catheter with an inner lumen of 1.5
      mm, is frequently used to perform the "child-in-mother" technique, which is also
      referred to as the "5-in-6" technique. A 6Fr or larger size guiding catheter can
      facilitate bioresorbable everolimus-eluting vascular scaffold (BVS) delivery. For
      tortuous lesions, the 5-in-6 technique can facilitate balloon catheters and the
      BVS in crossing tortuous lesions by increasing the back-up support. However, this
      maneuver couldn't be used for the larger size of BVS like 3.5-mm. Besides, it is
      necessary to preload the BVS into 5Fr ST01 guiding catheter to check whether this
      could really be done. We present a case in which a 5Fr ST01 catheter and the 5-in
      6 technique were successfully used in distal delivery of a BVS to cross a very
      tortuous right coronary artery lesion.

PMID- 29167624
TI  - Unique Ventricular Tachycardia Originating from the Right Bundle Branch.
AB  - Ventricular tachycardia (VT), a common arrhythmia, frequently originates from in
      the right ventricular outflow tract, left ventricular outflow tract, aortic
      sinus, and left ventricular papillary muscle but infrequently from the His
      Purkinje system, whereas the VT stemming from the right bundle branch has rarely
      been reported. Here we reported a case with of VT originating from the right
      bundle branch which was subsequently successfully treated with radiofrequency
      ablation and demonstrated the electrocardiac features of VT using an
      electrophysiological examination.

PMID- 29167625
TI  - From Cubist Simultaneity to Quantum Complementarity.
AB  - This article offers a contribution to the history of scientific ideas by
      proposing an epistemological argument supporting the assumption made by Miller
      whereby Niels Bohr has been influenced by cubism (Jean Metzinger) when he
      developed his non-intuitive complementarity principle. More specifically, this
      essay will identify the Bergsonian duree as the conceptual bridge between
      Metzinger and Bohr. Beyond this conceptual link between the painter and the
      physicist, this paper aims to emphasize the key role played by art in the
      development of human knowledge.

PMID- 29167626
TI  - Exploring spatial and temporal patterns of visceral leishmaniasis in endemic
      areas of Bangladesh.
AB  - Background: Visceral leishmaniasis is a considerable public health burden on the
      Indian subcontinent. The disease is highly endemic in the north-central part of
      Bangladesh, affecting the poorest and most marginalized communities. Despite the
      fact that visceral leishmaniasis (VL) results in mortality, severe morbidity, and
      socioeconomic stress in the region, the spatiotemporal dynamics of the disease
      have largely remained unexplored, especially in Bangladesh. Methods: Monthly VL
      cases between 2010 and 2014, obtained from subdistrict hospitals, were studied in
      this work. Both global and local spatial autocorrelation techniques were used to
      identify spatial heterogeneity of the disease. In addition, a spatial scan test
      was used to identify statistically significant space-time clusters in endemic
      locations of Bangladesh. Results: Global and local spatial autocorrelation
      indicated that the distribution of VL was spatially autocorrelated, exhibiting
      both contiguous and relocation-type of diffusion; however, the former was the
      main type of VL spread in the study area. The spatial scan test revealed that the
      disease had ten times higher incidence rate within the clusters than in non
      cluster zones. Both tests identified clusters in the same geographic areas,
      despite the differences in their algorithm and cluster detection approach.
      Conclusion: The cluster maps, generated in this work, can be used by public
      health officials to prioritize areas for intervention. Additionally, initiatives
      to control VL can be handled more efficiently when areas of high risk of the
      disease are known. Because global environmental change is expected to shift the
      current distribution of vectors to new locations, the results of this work can
      help to identify potentially exposed populations so that adaptation strategies
      can be formulated.

PMID- 29167627
TI  - The importance of human population characteristics in modeling Aedes aegypti
      distributions and assessing risk of mosquito-borne infectious diseases.
AB  - Background: The mosquito Aedes aegypti has long been a vector for human illness
      in the Southeastern United States. In the past, it has been responsible for
      outbreaks of dengue, chikungunya, and yellow fever and, very recently, the Zika
      virus that has been introduced to the region. Multiple studies have modeled the
      geographic distribution of Ae. aegypti as a function of climate factors; however,
      this ignores the importance of humans to the anthropophilic biter. Furthermore,
      Ae. aegypti thrives in areas where humans have created standing water sites, such
      as water storage containers and trash. As models are developed to examine the
      potential impact of climate change, it becomes increasingly important to include
      the most comprehensive set of predictors possible. Results: This study uses
      Maxent, a species distribution model, to evaluate the effects of adding poverty
      and population density to climate-only models. Performance was evaluated through
      model fit statistics, such as AUC, omission, and commission, as well as
      individual variable contributions and response curves. Models which included both
      population density and poverty exhibited better predictive power and produced
      more precise distribution maps. Furthermore, the two human population
      characteristics accounted for much of the model contribution-more so than climate
      variables. Conclusions: Modeling mosquito distributions without accounting for
      their dependence on local human populations may miss factors that are very
      important to niche realization and subsequent risk of infection for humans.
      Further research is needed to determine if additional human characteristics
      should be evaluated for model inclusion.

PMID- 29167628
TI  - A comparative study of job satisfaction among nurses,
      psychologists/psychotherapists and social workers working in Quebec mental health
      teams.
AB  - Background: This study identified multiple socio-professional and team
      effectiveness variables, based on the Input-Mediator-Output-Input (IMOI) model,
      and tested their associations with job satisfaction for three categories of
      mental health professionals (nurses, psychologists/psychotherapists, and social
      workers). Methods: Job satisfaction was assessed with the Job Satisfaction
      Survey. Independent variables were classified into four categories: 1) Socio
      professional Characteristics; 2) Team Attributes; 3) Team Processes; and 4) Team
      Emergent States. Variables were entered successively, by category, into a
      hierarchical regression model. Results: Team Processes contributed the greatest
      number of variables to job satisfaction among all professional groups, including
      team support which was the only significant variable common to all three types of
      professionals. Greater involvement in the decision-making process, and lower
      levels of team conflict (Team Processes) were associated with job satisfaction
      among nurses and social workers. Lower seniority on team (Socio-professional
      Characteristics), and team collaboration (Team Processes) were associated with
      job satisfaction among nurses, as was belief in the advantages of
      interdisciplinary collaboration (Team Emergent States) among psychologists.
      Knowledge sharing (Team Processes) and affective commitment to the team (Team
      Emergent States) were associated with job satisfaction among social workers.
      Conclusions: Results suggest the need for mental health decision-makers and team
      managers to offer adequate support to mental health professionals, to involve
      nurses and social workers in the decision-making process, and implement
      procedures and mechanisms favourable to the prevention or resolution of team
      conflict with a view toward increasing job satisfaction among mental health
      professionals.

PMID- 29167629
TI  - The Effects of Phacoemulsification and Intraocular Lens Implantation on
      Anatomical and Functional Parameters in Patients with Primary Angle Closure: A
      Prospective Study. (An American Ophthalmological Society Thesis).
AB  - Purpose: To investigate the clinical, anatomical, and patient-reported outcomes
      of phacoemulsification (PE) with intraocular lens implantation performed to treat
      primary angle closure (PAC) and primary angle-closure glaucoma (PACG). Methods:
      Patients were evaluated at baseline and at 6 months after PE. The examination
      included visual acuity, intraocular pressure (IOP), visual field, optic nerve
      head, endothelial cell count (ECC), aqueous depth, and ocular biometric
      parameters. Patient-reported visual function and health status were assessed.
      Coprimary outcome measures were IOP changes, angle widening, and patient-reported
      visual function; secondary outcome measures were visual acuity changes, use of
      IOP-lowering medications, and complications. Univariate and multivariate analyses
      were performed to determine the predictors of IOP change. Results: Thirty-nine
      cases were identified, and postoperative data were analyzed for 59 eyes, 39 with
      PACG and 20 with PAC. Globally, PE resulted in a mean reduction in IOP of -6.33
      mm Hg (95% CI, -8.64 to -4.01, P<.001). Aqueous depth and angle measurements
      improved (P<.01), whereas ECC significantly decreased (P<.001). Both corrected
      and uncorrected visual acuity improved (P<.01). The EQ visual analog scale did
      not change (P=.16), but VFQ-25 improved (P<.01). The IOP-lowering effect of PE
      was greater in the PACG compared to the PAC group (P=.04). In both groups,
      preoperative IOP was the most significant predictor of IOP change (P<.01). No
      sight-threatening complications were recorded. Conclusions: Our data support the
      usefulness of PE in lowering the IOP in patients with PAC and PACG. Although PE
      resulted in several anatomical and patient-reported visual improvements, we
      observe that a marked decrease in ECC should be carefully weighed before surgery.

PMID- 29167630
TI  - Family-Directed Cognitive Adaptation Pilot: Teaching Cognitive Adaptation to
      Families of Individuals with Schizophrenia.
AB  - Cognitive deficits are a major determinant of functional outcome in
      schizophrenia. A promising treatment involves teaching individuals to use
      cognitive adaptation strategies to minimize the functional impact of cognitive
      difficulties. We developed Family Directed Cognitive Adaptation (FCA) to train
      caregivers to help their relatives with schizophrenia use cognitive adaptations
      to improve living skills. The goal of this open pilot trial was to examine the
      feasibility of FCA. Ten adults with schizophrenia, each with at least one
      relative, participated in FCA and were evaluated at baseline, post-treatment, and
      6-month follow-up. Domains assessed included adaptive functioning, psychiatric
      symptoms, school/work involvement, hospitalizations, family burden, and treatment
      satisfaction. Participants reported high levels of satisfaction with FCA, and all
      families completed the 16-session intervention. Relatives reported reduced burden
      at termination and follow-up. No participants were hospitalized during the
      treatment or follow-up period, and rates of work/school involvement increased
      from 30% at baseline to 50% at the end of treatment and follow-up. Individuals
      improved in negative symptoms and adaptive functioning over the course of
      treatment, but these gains were not maintained. This pilot provides preliminary
      support for the acceptability and feasibility of FCA, and points to the need to
      address the maintenance of treatment gains after termination.

PMID- 29167632
TI  - 2015: an eventful year for the Metabolomics Society.

PMID- 29167631
TI  - Towards eco-friendly crop protection: natural deep eutectic solvents and
      defensive secondary metabolites.
AB  - With mounting concerns over health and environmental effects of pesticides, the
      search for environmentally acceptable substitutes has amplified. Plant secondary
      metabolites appear in the horizon as an attractive solution for green crop
      protection. This paper reviews the need for changes in the techniques and
      compounds that, until recently, have been the mainstay for dealing with pest
      insects. Here we describe and discuss main strategies for selecting plant-derived
      metabolites as candidates for sustainable agriculture. The second part surveys
      ten important insecticidal compounds, with special emphasis on those involved in
      human health. Many of these insecticidal metabolites, however, are crystalline
      solids with limited solubility which might potentially hamper commercial
      formulation. As such, we introduce the concept of natural deep eutectic solvents
      for enhancing solubility and stability of such compounds. The concept, principles
      and examples of green pest control discussed here offer a new suite of
      environmental-friendly tools designed to promote and adopt sustainable
      agriculture.

PMID- 29167633
TI  - Integrating Brain Science and Law: Neuroscientific Evidence and Legal
      Perspectives on Protecting Individual Liberties.
AB  - Advances in neuroscientific techniques have found increasingly broader
      applications, including in legal neuroscience (or "neurolaw"), where experts in
      the brain sciences are called to testify in the courtroom. But does the incursion
      of neuroscience into the legal sphere constitute a threat to individual
      liberties? And what legal protections are there against such threats? In this
      paper, we outline individual rights as they interact with neuroscientific
      methods. We then proceed to examine the current uses of neuroscientific evidence,
      and ultimately determine whether the rights of the individual are endangered by
      such approaches. Based on our analysis, we conclude that while federal evidence
      rules constitute a substantial hurdle for the use of neuroscientific evidence,
      more ethical safeguards are needed to protect against future violations of
      fundamental rights. Finally, we assert that it will be increasingly imperative
      for the legal and neuroscientific communities to work together to better define
      the limits, capabilities, and intended direction of neuroscientific methods
      applicable for use in law.

PMID- 29167635
TI  - Physical Exercise Promotes Novel Object Recognition Memory in Spontaneously
      Hypertensive Rats after Ischemic Stroke by Promoting Neural Plasticity in the
      Entorhinal Cortex.
AB  - Cerebral ischemia leads to memory impairment, and several studies have indicated
      that physical exercise (PE) has memory-improving effects after ischemia. This
      study was designed to further explore the specific role of PE in novel object
      recognition (NOR) memory after stroke and the exact cortical regions in which
      memory is restored by PE. Spontaneously hypertensive rats (SHR) were subjected to
      transient middle cerebral artery occlusion (tMCAO) or sham surgery, followed by
      26 days of PE starting on day 3 post-tMCAO. Thereafter, infarct volume,
      neurobehavioral outcome and NOR memory were assessed. Immunofluorescence staining
      and Luxol Fast Blue (LFB) staining were performed in the prefrontal cortex,
      entorhinal cortex and corpus callosum regions. Western blot analysis was
      performed to detect expressions of Nestin, Bcl-2 and SYN proteins in the
      entorhinal cortex. After tMCAO, NOR memory impairment was found in SHR. Rats
      subjected to PE post-tMCAO showed increased discrimination ratio, as well as
      significant decreases in infarct volumes and modified neurological severity
      scores (mNSS), when compared with tMCAO rats without PE. After stroke, NeuN
      positive cell number was drastically reduced in the entorhinal cortex, rather
      than in the prefrontal cortex. Ischemic stroke had no impact on myelin and
      phospholipids, and the ratio of SMI-32/MBP in the corpus callosum. PE increased
      NeuN, Nestin, Ki67, MBP, SYN, PSD-95 and Bcl-2 expressions in the entorhinal
      cortex, while TUNEL and SMI-32 expressions were decreased. In conclusion, the NOR
      memory-improving capacity promoted by PE was closely related to neuronal cell
      proliferation and synaptic plasticity of the entorhinal cortex.

PMID- 29167634
TI  - Circular RNAs: A Novel Player in Development and Disease of the Central Nervous
      System.
AB  - Circular RNAs (circRNAs) own unique capabilities to communicate with nucleic
      acids and ribonucleoproteins and are emerging as indispensable compositions of
      the regulatory messages encoded in the genome. Due to lack of 3' termini,
      circRNAs are more resistant to degradation by exonuclease RNase R and possess
      greater stability than linear RNAs. Moreover, circRNAs can act as microRNA
      (miRNA) sponge and affect messenger RNA (mRNA) splicing and transcription. By
      virtue of their great stability and elaborate regulatory mechanisms of gene
      expression, circRNAs play important roles in certain physiological activities.
      The development, homeostasis and stress response of the central nervous system
      (CNS) depend upon precise temporal and spatial regulation of gene networks.
      Moreover, emerging evidence has revealed that circRNAs are spatiotemporally
      regulated and dynamically expressed during brain development; therefore, they can
      exert significant influences on CNS development and diseases. In this review, we
      highlight the biogenesis of circRNAs and their central roles in regulation of CNS
      development and diseases.

PMID- 29167636
TI  - Preventive Strength of Dyadic Social Interaction against
      Reacquisition/Reexpression of Cocaine Conditioned Place Preference.
AB  - The reorientation away from drugs of abuse and toward social interaction is a
      highly desirable but as yet elusive goal in the therapy of substance dependence.
      We could previously show that cocaine preferring Sprague-Dawley rats which
      engaged in only four 15 min episodes of dyadic social interaction (DSI) did not
      reacquire and reexpress cocaine conditioned place preference (CPP) after a single
      cocaine exposure. In the present study, we investigated how strong this
      preventive effect of DSI is. In corroboration of our previous findings in rats,
      four 15 min DSI episodes prevented the reacquisition/reexpression of cocaine CPP
      in mice. However, this effect was only observed if only one cocaine conditioning
      session (15 min) was used. If mice were counterconditioned with a total of four
      cocaine sessions, the cocaine CPP reemerged. Interestingly, the opposite also
      held true: in mice that had acquired/expressed cocaine CPP, one conditioning
      session with DSI did not prevent the persistence of cocaine CPP, whereas four DSI
      conditioning sessions reversed CPP for 15 mg/kg intraperitoneal cocaine. Of note,
      this cocaine dose was a strong reward in C57BL/6J mice, causing CPP in all tested
      animals. Our findings suggest that both the reversal (reconditioning) of CPP from
      cocaine to DSI as well as that from DSI to cocaine requires four conditioning
      sessions. As previously shown in C57BL/6 mice from the NIH substrain, mice from
      the Jackson substrain also showed a greater relative preference for 15 mg/kg
      intraperitoneal cocaine over DSI, whereas Sprague-Dawley rats were equally
      attracted to contextual stimuli associated with this cocaine dose and DSI. Also
      in corroboration of previous findings, both C57BL/6J mice and experimenters
      several generations removed from the original ones produced CPP for DSI to a
      lesser degree than Sprague-Dawley rats. Our findings demonstrate the robustness
      of our experimental model across several subject- and experimenter generations in
      two rodent genus (i.e., mouse and rat) and allow the quantification of the
      strength (i.e., persistence) of the preventive effect of DSI against the
      reacquisition/reexpression of cocaine CPP, arguably a model for cocaine relapse.

PMID- 29167637
TI  - Variations in Static Force Control and Motor Unit Behavior with Error
      Amplification Feedback in the Elderly.
AB  - Error amplification (EA) feedback is a promising approach to advance visuomotor
      skill. As error detection and visuomotor processing at short time scales decline
      with age, this study examined whether older adults could benefit from EA feedback
      that included higher-frequency information to guide a force-tracking task.
      Fourteen young and 14 older adults performed low-level static isometric force
      tracking with visual guidance of typical visual feedback and EA feedback
      containing augmented high-frequency errors. Stabilogram diffusion analysis was
      used to characterize force fluctuation dynamics. Also, the discharge behaviors of
      motor units and pooled motor unit coherence were assessed following the
      decomposition of multi-channel surface electromyography (EMG). EA produced
      different behavioral and neurophysiological impacts on young and older adults.
      Older adults exhibited inferior task accuracy with EA feedback than with typical
      visual feedback, but not young adults. Although stabilogram diffusion analysis
      revealed that EA led to a significant decrease in critical time points for both
      groups, EA potentiated the critical point of force fluctuations [Formula: see
      text], short-term effective diffusion coefficients (Ds), and short-term exponent
      scaling only for the older adults. Moreover, in older adults, EA added to the
      size of discharge variability of motor units and discharge regularity of
      cumulative discharge rate, but suppressed the pooled motor unit coherence in the
      13-35 Hz band. Virtual EA alters the strategic balance between open-loop and
      closed-loop controls for force-tracking. Contrary to expectations, the prevailing
      use of closed-loop control with EA that contained high-frequency error
      information enhanced the motor unit discharge variability and undermined the
      force steadiness in the older group, concerning declines in physiological
      complexity in the neurobehavioral system and the common drive to the motoneuronal
      pool against force destabilization.

PMID- 29167638
TI  - Hyper-Transcranial Alternating Current Stimulation: Experimental Manipulation of
      Inter-Brain Synchrony.
AB  - We walk together, we watch together, we win together: Interpersonally coordinated
      actions are omnipresent in everyday life, yet the associated neural mechanisms
      are not well understood. Available evidence suggests that the synchronization of
      oscillatory activity across brains may provide a mechanism for the temporal
      alignment of actions between two or more individuals. In an attempt to provide a
      direct test of this hypothesis, we applied transcranial alternating current
      stimulation simultaneously to two individuals (hyper-tACS) who were asked to drum
      in synchrony at a set pace. Thirty-eight female-female dyads performed the dyadic
      drumming in the course of 3 weeks under three different hyper-tACS stimulation
      conditions: same-phase-same-frequency; different-phase-different-frequency; sham.
      Based on available evidence and theoretical considerations, stimulation was
      applied over right frontal and parietal sites in the theta frequency range. We
      predicted that same-phase-same-frequency stimulation would improve interpersonal
      action coordination, expressed as the degree of synchrony in dyadic drumming,
      relative to the other two conditions. Contrary to expectations, both the same
      phase-same-frequency and the different-phase-different-frequency conditions were
      associated with greater dyadic drumming asynchrony relative to the sham
      condition. No influence of hyper-tACS on behavioral performance was seen when
      participants were asked to drum separately in synchrony to a metronome.
      Individual and dyad preferred drumming tempo was also unaffected by hyper-tACS.
      We discuss limitations of the present version of the hyper-tACS paradigm, and
      suggest avenues for future research.

PMID- 29167639
TI  - Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network
      Effective Connectivity in Amnestic Mild Cognitive Impairment.
AB  - Alzheimer's disease (AD) and its prodromal state amnestic mild cognitive
      impairment (aMCI) are characterized by widespread abnormalities in inter-areal
      white matter fiber pathways and parallel disruption of default mode network (DMN)
      resting state functional and effective connectivity. In healthy subjects, DMN and
      task positive network interaction are modulated by the thalamus suggesting that
      abnormal task-based DMN deactivation in aMCI may be a consequence of impaired
      thalamo-cortical white matter circuitry. Thus, this article uses a multimodal
      approach to assess white matter integrity between thalamus and DMN components and
      associated effective connectivity in healthy controls (HCs) relative to aMCI
      patients. Twenty-six HC and 20 older adults with aMCI underwent structural,
      functional and diffusion MRI scanning using the high angular resolution diffusion
      weighted acquisition protocol. The DMN of each subject was identified using
      independent component analysis (ICA) and resting state effective connectivity was
      calculated between thalamus and DMN nodes. White matter integrity changes between
      thalamus and DMN were investigated with constrained spherical deconvolution (CSD)
      tractography. Significant structural deficits in thalamic white matter projection
      fibers to posterior DMN components posterior cingulate cortex (PCC) and lateral
      inferior parietal lobe (IPL) were identified together with significantly reduced
      effective connectivity from left thalamus to left IPL. Crucially, impaired
      thalamo-cortical white matter circuitry correlated with memory performance.
      Disrupted thalamo-cortical structure was accompanied by significant reductions in
      IPL and PCC cortico-cortical effective connectivity. No structural deficits were
      found between DMN nodes. Abnormal posterior DMN activity may be driven by changes
      in thalamic white matter connectivity; a view supported by the close anatomical
      and functional association of thalamic nuclei effected by AD pathology and the
      posterior DMN nodes. We conclude that dysfunctional posterior DMN activity in
      aMCI is consistent with disrupted cortico-thalamo-cortical processing and
      thalamic-based dissemination of hippocampal disease agents to cortical hubs.

PMID- 29167640
TI  - Visceral Fat Dysfunctions in the Rat Social Isolation Model of Psychosis.
AB  - Medication with neuroleptics has been associated with adipose tissue dysfunctions
      and, in particular, with increased visceral fat amount. However, several studies
      suggested that antipsychotic treatment might not be the main responsible of fat
      mass accumulation, as this has been also described in not treated psychotic
      patients. One of the most used "drug-free" rodent models of psychosis is the
      social isolation rearing of young adult rats, which provides a non-pharmacologic
      method of inducing long-term alterations reminiscent of symptoms seen in
      psychotic patients. Recent data highlighted a crucial role of redox imbalance in
      adipose tissue dysfunctions, in terms of decreased antioxidant defense and
      increased reactive oxygen species (ROS). Here, we investigated possible oxidative
      stress-related biomolecular alterations associated with visceral fat increase in
      7 week isolated rats. To this purpose, we quantified total and visceral fat
      amount by using dual-energy X-ray (DEXA) absorptiometry. On visceral fat, we
      analyzed the expression of specific ROS-producer genes (Nox1, Nox4, Hmox-1),
      antioxidant enzymes (Prdx1 and Ucp-1) and oxidative stress-induced damage markers
      (Cidea, Slc2a4, and Acacb). The impact of oxidative stress on beta3-adrenergic
      receptors (Adrb3), at both mRNA and protein level, was also assessed. We found
      that 7 weeks of social isolation induced an increase in total and visceral fat,
      associated with a decrease in Prdx1 (mRNA and protein) as well as Ucp-1 mRNA
      levels and an enhanced expression of Nox1 (mRNA and protein) and Hmox-1 mRNA. No
      differences were detected in Nox4 mRNA levels between grouped and isolated
      animals. Elevations in Cidea, Slc2a4, and Acacb expression in visceral fat of
      isolated animals accounted for oxidative stress-related damage in this tissue,
      further associated with a significant increase in Adrb3 mRNA and protein. Our
      results provide a novel understanding of the pathological link existing among
      psychosocial stress-induced psychosis, adipose tissue dysfunctions and redox
      imbalance, opening new therapeutic perspectives for the treatment of alterations
      in peripheral tissues associated with this mental disorder.

PMID- 29167641
TI  - alpha7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene
      Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way.
AB  - The existence of a cholinergic anti-inflammatory pathway negatively modulating
      the inflammatory and immune responses in various clinical conditions and
      experimental models has long been postulated. In particular, the protective
      involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs) has been
      proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS
      induced colitis. However, the role of alpha7 nAChRs stimulation is still
      controversial and the potential contribution of alpha4beta2 nAChRs has never been
      explored in this experimental condition. Our aims were therefore to
      pharmacologically investigate the role played by both alpha7 and alpha4beta2
      nAChRs in the modulation of the local and systemic inflammatory responses
      activated in TNBS-induced colitis in mice and to assess the involvement of the
      spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely
      treated with various subcutaneous doses of highly selective agonists (AR-R17779
      and TC-2403) and antagonists (methyllycaconitine and dihydro-beta-erythroidine)
      of alpha7 and alpha4beta2 nAChRs, respectively, or with sulfasalazine 50 mg/kg
      per os and clinical and inflammatory responses were evaluated by means of
      biochemical, histological and flow cytometry assays. alpha4beta2 ligands evoked
      weak and contradictory effects, while alpha7 nAChR agonist AR-R17779 emerged as
      the most beneficial treatment, able to attenuate several local markers of colitis
      severity and to revert the rise in splenic T-cells and in colonic inflammatory
      cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its
      protective effects, demonstrating for the first time that, in TNBS-model of
      experimental colitis, the anti-inflammatory effect of exogenous alpha7 nAChR
      stimulation is strictly spleen-dependent. Our findings showed that the selective
      alpha7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of
      intestinal inflammation characterized by activation of the adaptive immune system
      and that the spleen is essential to mediate this cholinergic protection.

PMID- 29167642
TI  - An Update on AMPK in Hydrogen Sulfide Pharmacology.
AB  - Hydrogen sulfide (H2S), the third bio-active gasotransmitter, is produced
      endogenously and tightly involved in the pathogenesis and treatment for various
      diseases. Adenosine 5'-monophosphate-activated protein kinase (AMPK) plays a
      paramount role in maintaining cellular energetic balance. Increasing evidences
      have also suggested AMPK as a novel modulator in multiple pathological
      conditions. In this paper, we will review the biological principles of H2S and
      AMPK, and most importantly, the recent discoveries regarding AMPK-mediated
      pharmacological actions of H2S. Emphasis will be laid on AMPK/H2S interactions in
      the cardiovascular system, autophagy, diabetic complications, and inflammation.
      In most cases described in this article, by promoting AMPK activation, H2S exerts
      cytoprotective effects or therapeutic potentials, though there remain some
      controversies before we can fully understand the involved mechanisms. Further
      researches are in need to investigate more closely any relationship between H2S
      and AMPK, and to put forward the development of H2S donors for clinical
      application.

PMID- 29167643
TI  - Post-inflammatory Ileitis Induces Non-neuronal Purinergic Signaling Adjustments
      of Cholinergic Neurotransmission in the Myenteric Plexus.
AB  - Uncoupling between ATP overflow and extracellular adenosine formation changes
      purinergic signaling in post-inflammatory ileitis. Adenosine neuromodulation
      deficits were ascribed to feed-forward inhibition of ecto-5'-nucleotidase/CD73 by
      high extracellular adenine nucleotides in the inflamed ileum. Here, we
      hypothesized that inflammation-induced changes in cellular density may also
      account to unbalance the release of purines and their influence on
      [3H]acetylcholine release from longitudinal muscle-myenteric plexus preparations
      of the ileum of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-treated rats. The
      population of S100beta-positive glial cells increase, whereas Ano-1-positive
      interstitial cells of Cajal (ICCs) diminished, in the ileum 7-days after the
      inflammatory insult. In the absence of changes in the density of VAChT-positive
      cholinergic nerves detected by immunofluorescence confocal microscopy, the
      inflamed myenteric plexus released smaller amounts of [3H]acetylcholine which
      also became less sensitive to neuronal blockade by tetrodotoxin (1 MUM). Instead,
      [3H]acetylcholine release was attenuated by sodium fluoroacetate (5 mM),
      carbenoxolone (10 MUM) and A438079 (3 MUM), which prevent activation of glial
      cells, pannexin-1 hemichannels and P2X7 receptors, respectively. Sodium
      fluoroacetate also decreased ATP overflow without significantly affecting the
      extracellular adenosine levels, thus indicating that surplus ATP release
      parallels reactive gliosis in post-inflammatory ileitis. Conversely, loss of ICCs
      may explain the lower amounts of adenosine detected in TNBS-treated preparations,
      since blockade of Cav3 (T-type) channels existing in ICCs with mibefradil (3 MUM)
      or inhibition of the equilibrative nucleoside transporter 1 with dipyridamole
      (0.5 MUM), both decreased extracellular adenosine. Data indicate that post
      inflammatory ileitis operates a shift on purinergic neuromodulation reflecting
      the upregulation of ATP-releasing enteric glial cells and the depletion of ICCs
      accounting for decreased adenosine overflow via equilibrative nucleoside
      transporters.

PMID- 29167644
TI  - LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation.
AB  - Rationale: Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid
      diethylamide (LSD) and related compounds such as psilocybin has previously been
      shown to increase primary process thinking - an ontologically and evolutionary
      early, implicit, associative, and automatic mode of thinking which is typically
      occurring during altered states of consciousness such as dreaming. However, it is
      still largely unknown whether LSD induces primary process thinking under placebo
      controlled, standardized experimental conditions and whether these effects are
      related to subjective experience and 5-HT2A receptor activation. Therefore, this
      study aimed to test the hypotheses that LSD increases primary process thinking
      and that primary process thinking depends on 5-HT2A receptor activation and is
      related to subjective drug effects. Methods: Twenty-five healthy subjects
      performed an audio-recorded mental imagery task 7 h after drug administration
      during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with
      the 5-HT2A receptor antagonist ketanserin (40 mg orally). The main outcome
      variable in this study was primary index (PI), a formal measure of primary
      process thinking in the imagery reports. State of consciousness was evaluated
      using the Altered State of Consciousness (5D-ASC) rating scale. Results: LSD,
      compared with placebo, significantly increased primary index (p < 0.001,
      Bonferroni-corrected). The LSD-induced increase in primary index was positively
      correlated with LSD-induced disembodiment (p < 0.05, Bonferroni-corrected), and
      blissful state (p < 0.05, Bonferroni-corrected) on the 5D-ASC. Both LSD-induced
      increases in primary index and changes in state of consciousness were fully
      blocked by ketanserin. Conclusion: LSD induces primary process thinking via
      activation of 5-HT2A receptors and in relation to disembodiment and blissful
      state. Primary process thinking appears to crucially organize inner experiences
      during both dreams and psychedelic states of consciousness.

PMID- 29167645
TI  - Improving Cardiometabolic Health with Diet, Physical Activity, and Breaking Up
      Sitting: What about Sleep?
AB  - Cardiometabolic disease poses a serious health and economic burden worldwide and
      its prevalence is predicted to increase. Prolonged sitting, lack of physical
      activity, poor diet, and short sleep duration are ubiquitous behaviors in modern
      society, and all are independent risk factors in the development of
      cardiometabolic disease. Existing evidence demonstrates that breaking up
      prolonged periods of sitting is beneficial for cardiometabolic health, however,
      studies have not controlled for prior sleep duration. This article examines how
      prolonged sitting and short sleep duration independently contribute to
      cardiometabolic risk, and how breaking up sitting and obtaining adequate sleep
      may reduce this risk. We suggest that as prolonged sitting and short sleep
      duration influence the same cardiometabolic parameters, there is potential for
      short sleep to attenuate the positive impact of breaking up prolonged sitting
      with physical activity. Likewise, breaking up prolonged sitting and obtaining
      adequate sleep together could improve predictors of cardiometabolic disease,
      i.e., the combined effect may be stronger than either alone. To explore these
      perspectives, we propose a research agenda to investigate the relationship
      between breaking up prolonged sitting with physical activity and short sleep
      duration. This will provide an evidence-base for informing the design of
      interventions to reduce the burden of cardiometabolic disease on communities
      worldwide.

PMID- 29167647
TI  - Corrigendum: The Electrogenic Na+/K+ Pump Is a Key Determinant of Repolarization
      Abnormality Susceptibility in Human Ventricular Cardiomyocytes: A Population
      Based Simulation Study.
AB  - [This corrects the article on p. 278 in vol. 8, PMID: 28529489.].

PMID- 29167648
TI  - Paired Associative Stimulation of the Temporal Cortex: Effects on the Auditory
      Steady-State Response.
AB  - Background: Paired associative stimulation (PAS) is the repeated combination of a
      sensory stimulus with transcranial magnetic stimulation (TMS) in close temporal
      association. Recently, a study demonstrated that PAS of an auditory stimulus
      together with TMS of the temporal cortex is capable of changing the amplitude of
      auditory evoked potentials (AEP). Objective: This study examined the influence of
      tone duration and habituation in temporal cortex PAS as elicited by 40 and 20 Hz
      amplitude modulated auditory steady-state responses (aSSR). Methods: Eighteen
      subjects participated in two experiments, including two PAS protocols each, which
      consisted of 200 auditory stimuli (4 kHz) paired with temporal cortex TMS with an
      interstimulus interval (ISI) of 45 ms between tone onset and TMS pulse, delivered
      at 0.1 Hz. Experiment 1 compared auditory stimuli with different lengths [PAS (23
      ms) vs. PAS (400 ms)]. Experiment 2 investigated verum vs. sham PAS. aSSR for the
      paired tone (4 kHz) and a control tone (1 kHz) were measured pre- and post
      interventional-using 40 Hz aSSR in experiment 1 and both 20 and 40 Hz aSSR in
      experiment 2. Results: A statistically significant, sham-controlled decrease in
      amplitude was observed for the 20 Hz aSSR using the 4 kHz PAS carrier frequency
      in experiment 2. Conclusion: Frequency-specific effects for the 20 Hz aSSR
      confirm the feasibility of auditory PAS and highlight the secondary auditory
      cortex as its target site, introducing new possible treatment protocols for
      patients suffering from tinnitus. The amplitude decrease can be explained by
      principles of spike timing-dependent plasticity and the superposition model of
      aSSR.

PMID- 29167649
TI  - The Effect of EMDR and CBT on Low Self-esteem in a General Psychiatric
      Population: A Randomized Controlled Trial.
AB  - Although low self-esteem has been found to be an important factor in the
      development and maintenance of psychopathology, surprisingly little is known
      about its treatment. This study investigated the effectiveness of Eye Movement
      Desensitization and Reprocessing (EMDR) therapy and Cognitive Behavioural Therapy
      (CBT), regarding their capacities in enhancing self-esteem in a general
      psychiatric secondary health care population. A randomized controlled trial with
      two parallel groups was used. Participants were randomly allocated to either 10
      weekly sessions of EMDR (n = 15) or CBT (n = 15). They were assessed pre
      treatment, after each session, post treatment and at 3 months follow-up on self
      esteem (Rosenberg Self-esteem Scale and Credibility of Core Beliefs),
      psychological symptoms (Brief Symptom Inventory), social anxiety, and social
      interaction (Inventory of Interpersonal Situations) (IIS). The data were analyzed
      using repeated measures ANOVA for the complete cases (n = 19) and intention-to
      treat (n = 30) to examine differences over time and between conditions. Both
      groups, EMDR as well as CBT, showed significant improvements on self-esteem,
      increasing two standard deviations on the main parameter (RSES). Furthermore, the
      results showed significant reductions in general psychiatric symptoms. The
      effects were maintained at 3 months follow-up. No between-group differences could
      be detected. Although the small sample requires to exercise caution in the
      interpretation of the findings, the results suggest that, when offering an
      adequate number of sessions, both EMDR and CBT have the potential to be effective
      treatments for patients with low self-esteem and a wide range of comorbid
      psychiatric conditions. This study was registered at www.trialregister.nl with
      identifier NTR4611.

PMID- 29167646
TI  - Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications.
AB  - Palmitic acid (PA) has been for long time negatively depicted for its putative
      detrimental health effects, shadowing its multiple crucial physiological
      activities. PA is the most common saturated fatty acid accounting for 20-30% of
      total fatty acids in the human body and can be provided in the diet or
      synthesized endogenously via de novo lipogenesis (DNL). PA tissue content seems
      to be controlled around a well-defined concentration, and changes in its intake
      do not influence significantly its tissue concentration because the exogenous
      source is counterbalanced by PA endogenous biosynthesis. Particular
      physiopathological conditions and nutritional factors may strongly induce DNL,
      resulting in increased tissue content of PA and disrupted homeostatic control of
      its tissue concentration. The tight homeostatic control of PA tissue
      concentration is likely related to its fundamental physiological role to
      guarantee membrane physical properties but also to consent protein
      palmitoylation, palmitoylethanolamide (PEA) biosynthesis, and in the lung an
      efficient surfactant activity. In order to maintain membrane phospholipids (PL)
      balance may be crucial an optimal intake of PA in a certain ratio with
      unsaturated fatty acids, especially PUFAs of both n-6 and n-3 families. However,
      in presence of other factors such as positive energy balance, excessive intake of
      carbohydrates (in particular mono and disaccharides), and a sedentary lifestyle,
      the mechanisms to maintain a steady state of PA concentration may be disrupted
      leading to an over accumulation of tissue PA resulting in dyslipidemia,
      hyperglycemia, increased ectopic fat accumulation and increased inflammatory tone
      via toll-like receptor 4. It is therefore likely that the controversial data on
      the association of dietary PA with detrimental health effects, may be related to
      an excessive imbalance of dietary PA/PUFA ratio which, in certain
      physiopathological conditions, and in presence of an enhanced DNL, may further
      accelerate these deleterious effects.

PMID- 29167650
TI  - Social and Emotional Learning and Academic Achievement in Portuguese Schools: A
      Bibliometric Study.
AB  - Social and Emotional Learning (SEL) is an educational movement that is gaining
      ground throughout the world. We can define SEL as the capacity to recognize and
      manage emotions, solve problems effectively, and establish positive relationships
      with others. Research has demonstrated the significant role of SEL in promoting
      healthy student development and academic achievement. Extensive research confirms
      that SEL competencies: can be taught, that they promote positive development and
      reduce problem behaviors, and that they improve students' academic achievement
      and citizenship. At the international level, several rigorous studies have
      identified programs and practices that promote SEL. In Portugal, however, no
      review has yet been published regarding the implementation of SEL programs. Such
      a study would elucidate the current panorama of SEL programs in Portugal. This
      study aims to identify research on SEL programs implemented in Portuguese schools
      and the relationship of those programs with academic achievement. To this end, we
      have consulted the following databases: Scientific Repository of Open Access of
      Portugal (RCAAP), Online Knowledge Library (b-on), and Web of Science (WoS). The
      criteria were: (a) all time frames; (b) publications in either Portuguese or
      English; (c) programs that developed socio-emotional competencies in Portuguese
      schools; (d) academic levels including elementary, middle, and high school and
      (e) students of regular education. Few publications on SEL programs implemented
      in Portugal were found, although the recent decade has witnessed an upsurge of
      interest in the topic, principally that arising from academic research.

PMID- 29167651
TI  - Nonsuicidal Self-injury: A Systematic Review.
AB  - Objective: Nonsuicidal self-injury (NSSI) refers to the intentional self
      inflicted destruction of body tissue without suicidal intention and for purposes
      not socially sanctioned. Our paper presents an up-to-date overview on
      nonsuicidal, self-injurious behaviors. Method: In accordance with PRISMA
      guidelines, a systematic literature search was conducted across two databases,
      PubMed and PsycARTICLES, regarding the main features of NSSI with a focus on
      epidemiological and etiologic data, diagnostic criteria, and functions. All
      English articles, published between 1998 and 2016, were considered, and screened
      against a priori inclusion/exclusion criteria. The search terms include: self
      harm, self-injury, NSSI, epidemiology, comorbidity, gender, functions and DSM. We
      also examined the references of the retrieved articles. Results: NSSI is most
      common among adolescents and young adults, and the age of onset is reported to
      occur between 12 and 14 years. Comorbidity with borderline personality disorder
      (BPD) and eating disorders is often reported. DSM-5 includes NSSI as a condition
      requiring further study. This review gives an overview of the prevalence rates
      (7.5-46.5% adolescents, 38.9% university students, 4-23% adults) and main causes
      that appear to stem from childhood trauma, comorbidity with many other disorders
      and several functions of NSSI, and the potential independence of a NSSI disorder.
      Conclusion: Over the years, interest in NSSI grew to such an extent that an
      ongoing debate was instigated on whether NSSI should be considered as a diagnosis
      in its own right and given its own category. This paper provides an up-to-date
      overview on self-injury, what is known about it and what remains to be done.
      Clearly, our understanding of the main issues of NSSI has increased in last two
      decades. However, future researches is needed to examine the developmental
      trajectories, cultural backgrounds and shed light on the risk factors and
      functions as well as clarify its role as an independent diagnostic entity.

PMID- 29167652
TI  - Eye Contact and Fear of Being Laughed at in a Gaze Discrimination Task.
AB  - Current approaches conceptualize gelotophobia as a personality trait
      characterized by a disproportionate fear of being laughed at by others.
      Consistently with this perspective, gelotophobes are also described as neurotic
      and introverted and as having a paranoid tendency to anticipate derision and
      mockery situations. Although research on gelotophobia has significantly
      progressed over the past two decades, no evidence exists concerning the potential
      effects of gelotophobia in reaction to eye contact. Previous research has pointed
      to difficulties in discriminating gaze direction as the basis of possible
      misinterpretations of others' intentions or mental states. The aim of the present
      research was to examine whether gelotophobia predisposition modulates the effects
      of eye contact (i.e., gaze discrimination) when processing faces portraying
      several emotional expressions. In two different experiments, participants
      performed an experimental gaze discrimination task in which they responded, as
      quickly and accurately as possible, to the eyes' directions on faces displaying
      either a happy, angry, fear, neutral, or sad emotional expression. In particular,
      we expected trait-gelotophobia to modulate the eye contact effect, showing
      specific group differences in the happiness condition. The results of Study 1 (N
      = 40) indicated that gelotophobes made more errors than non-gelotophobes did in
      the gaze discrimination task. In contrast to our initial hypothesis, the
      happiness expression did not have any special role in the observed differences
      between individuals with high vs. low trait-gelotophobia. In Study 2 (N = 40), we
      replicated the pattern of data concerning gaze discrimination ability, even after
      controlling for individuals' scores on social anxiety. Furthermore, in our second
      experiment, we found that gelotophobes did not exhibit any problem with
      identifying others' emotions, or a general incorrect attribution of affective
      features, such as valence, intensity, or arousal. Therefore, this bias in
      processing gaze might be related to the global processes of social cognition.
      Further research is needed to explore how eye contact relates to the fear of
      being laughed at.

PMID- 29167653
TI  - What Drives Them to Drive?-Parents' Reasons for Choosing the Car to Take Their
      Children to School.
AB  - Children's school journeys have changed vastly during recent decades: More
      children are being driven to school in private cars instead of walking and
      cycling, with many who are entitled to a free school bus service still being
      driven. Earlier research into travel mode choice has often investigated how urban
      form impacts upon mode choice regarding school journeys-in particular how urban
      form hinders or enables the use of the active mode. This paper quantitatively
      explores parents' stated reasons for choosing the car and the relationship
      between these reasons and the decision to use the car to take their children to
      school. We additionally investigate the relationship between sociodemographic
      factors, distance, and both the stated reasons and the actual mode decision. A
      sample of 245 parents (194 women) of school children aged 10-15 in the County of
      Varmland in Sweden were included in the study. The results of PLS-SEM show that
      the factor Social convenience has a direct relationship with the frequency of car
      use indicating that the wish to accompany the child and the convenience of car
      impacts on car choice. If the child is not allowed to travel independently, the
      parents choose the car to take him/her to school. Sociodemographic factors had a
      direct relationship with the stated reasons, whereby parents with a higher level
      of education valued safety/security less. Quite surprisingly, distance (i.e.,
      environmental factor) did not affect car use, indicating that parents drive their
      children to school regardless of distance. By isolating the particular reasons
      for choosing the car, this paper focuses on a potentially important missing piece
      as regards finding out what motivates the increasing car usage in children's
      school journeys. An increased knowledge of what motivates the decision to take
      children by car is important for effective policies aimed at changing parents'
      inclination toward choosing the car.

PMID- 29167654
TI  - Dark Triad, Perceptions of Organizational Politics and Counterproductive Work
      Behaviors: The Moderating Effect of Political Skills.
AB  - The aim of this work focuses on the relationship among the Dark Triad
      (psychopathy, narcissism, and Machiavellianism), perceptions of organizational
      politics, political skills, and counterproductive work behavior. This study
      empirically tests the mediating role of perceptions of organizational politics in
      the relationship between the Dark Triad and counterproductive work behavior.
      Furthermore, the study investigates the moderating role of political skills in
      strengthening the link between the Dark Triad and the perceptions of
      organizational politics. A sample of 149 participants was randomly selected. To
      analyze the data of the present work, we employed a structural equation model
      using partial least square and PROCESS. From empirical findings, we imply an
      inference that perception of organizational politics partially mediates the Dark
      Triad's influence on the counterproductive work behavior. Moreover, the results
      identify the moderating role of political skills in strengthening the link
      between the Dark Triad and the perceptions of organizational politics. Empirical
      findings suggest important policy implications for the hospitality industry.

PMID- 29167655
TI  - An Individual Finger Gesture Recognition System Based on Motion-Intent Analysis
      Using Mechanomyogram Signal.
AB  - Motion-intent-based finger gesture recognition systems are crucial for many
      applications such as prosthesis control, sign language recognition, wearable
      rehabilitation system, and human-computer interaction. In this article, a motion
      intent-based finger gesture recognition system is designed to correctly identify
      the tapping of every finger for the first time. Two auto-event annotation
      algorithms are firstly applied and evaluated for detecting the finger tapping
      frame. Based on the truncated signals, the Wavelet packet transform (WPT)
      coefficients are calculated and compressed as the features, followed by a feature
      selection method that is able to improve the performance by optimizing the
      feature set. Finally, three popular classifiers including naive Bayes (NBC), K
      nearest neighbor (KNN), and support vector machine (SVM) are applied and
      evaluated. The recognition accuracy can be achieved up to 94%. The design and the
      architecture of the system are presented with full system characterization
      results.

PMID- 29167657
TI  - Choices Regarding Thrombolysis Are Modified by the Way to Transfer the Messages.
AB  - Although thrombolysis is the most effective medical treatment for acute ischemic
      stroke, many stroke patients eligible for thrombolysis miss this treatment as a
      result of delay or refusal by the patients and/or their proxies. To explore the
      influences of prognostic information for different intervals from stroke onset to
      the start of thrombolytic treatment (OTT) and other factors on the preferences of
      patients/proxies regarding thrombolytic therapy, a cross-sectional, discrete
      choice experiment was performed between August 2013 and September 2014. A total
      of 613 Chinese inpatients or their immediate family members were consecutively
      recruited at the Department of Neurology. After random assignment to a negative
      framing group or a positive-framing group, the subjects completed a series of
      surveys, including nine items about thrombolysis. Latent class analysis (LCA) was
      used to examine participants' preference paradigms for thrombolysis and to
      categorize the participants into different subgroups. Subsequently, regression
      analyses were conducted to explore predictors of categorization of the
      participants into each subgroup and to construct a thrombolytic decision-making
      model. LCA revealed an optimal 3-subgroup model including a consent to
      thrombolysis subgroup and objection to thrombolysis subgroups 1 and 2. Multiple
      regression analysis demonstrated that compared with assignment to the consent to
      thrombolysis subgroup, assignment to objection to thrombolysis subgroup 1 or 2
      could be predicted by different factors. chi2 tests indicated effects of framing
      and other factors on participants' choices regarding thrombolysis. Choices
      regarding thrombolysis were modified by not only prognostic information for
      different OTT intervals but also message framing, presentation format, and
      sociodemographic characteristics. To facilitate consent to thrombolysis,
      physicians should convey prognostic information to patients/proxies on the basis
      of patient OTT interval and should order the presentation of therapies according
      to the classification of patients/proxies. Individualized decision-making (IDM)
      might be an optimal strategy to increase the selection of thrombolysis, which
      providing important reference points for IDM in other clinical domains.

PMID- 29167656
TI  - Multivariate Analyses of Balance Test Performance, Vestibular Thresholds, and
      Age.
AB  - We previously published vestibular perceptual thresholds and performance in the
      Modified Romberg Test of Standing Balance in 105 healthy humans ranging from ages
      18 to 80 (1). Self-motion thresholds in the dark included roll tilt about an
      earth-horizontal axis at 0.2 and 1 Hz, yaw rotation about an earth-vertical axis
      at 1 Hz, y-translation (interaural/lateral) at 1 Hz, and z-translation (vertical)
      at 1 Hz. In this study, we focus on multiple variable analyses not reported in
      the earlier study. Specifically, we investigate correlations (1) among the five
      thresholds measured and (2) between thresholds, age, and the chance of failing
      condition 4 of the balance test, which increases vestibular reliance by having
      subjects stand on foam with eyes closed. We found moderate correlations (0.30
      0.51) between vestibular thresholds for different motions, both before and after
      using our published aging regression to remove age effects. We found that lower
      or higher thresholds across all threshold measures are an individual trait that
      account for about 60% of the variation in the population. This can be further
      distributed into two components with about 20% of the variation explained by
      aging and 40% of variation explained by a single principal component that
      includes similar contributions from all threshold measures. When only roll tilt
      0.2 Hz thresholds and age were analyzed together, we found that the chance of
      failing condition 4 depends significantly on both (p = 0.006 and p = 0.013,
      respectively). An analysis incorporating more variables found that the chance of
      failing condition 4 depended significantly only on roll tilt 0.2 Hz thresholds (p
      = 0.046) and not age (p = 0.10), sex nor any of the other four threshold
      measures, suggesting that some of the age effect might be captured by the fact
      that vestibular thresholds increase with age. For example, at 60 years of age,
      the chance of failing is roughly 5% for the lowest roll tilt thresholds in our
      population, but this increases to 80% for the highest roll tilt thresholds. These
      findings demonstrate the importance of roll tilt vestibular cues for balance,
      even in individuals reporting no vestibular symptoms and with no evidence of
      vestibular dysfunction.

PMID- 29167658
TI  - Atypical Electrophysiological Findings in a Patient with Acute Motor and Sensory
      Axonal Neuropathy.
AB  - Guillain-Barre syndrome (GBS) is an immune-mediated polyradiculoneuropathy with
      acute onset and rapid clinical worsening; early diagnosis and immunomodulating
      therapy can ameliorate the course of disease. During the first days, however,
      nerve conduction studies (NCSs) are not always conclusive. Here, we describe a 73
      year-old man presenting with progressive muscular weakness of the lower limbs,
      ascending to the upper limbs, accompanied by distal sensory disturbances.
      Neuroimaging of brain and spine and NCSs were unremarkable; cerebrospinal fluid
      analysis revealed no albuminocytologic dissociation. Based on typical clinical
      features, and on positivity for serum GD1b-IgM antibodies, GBS with proximal
      conduction failure at multiple radicular levels was postulated, and a standard
      regime of intravenous immunoglobulin was administered. Four weeks later, the
      patient presented with flaccid tetraparesis, areflexia, and reduction of position
      sense, tingling paresthesias, and initial respiratory distress. Repeat NCS still
      revealed almost normal findings, except for the disappearance of right ulnar
      nerve F-waves. A few days thereafter, the patient developed severe respiratory
      insufficiency requiring mechanical ventilation for 2 weeks. On day 50, NCS
      revealed for the first time markedly reduced compound muscle action potentials
      and sensory nerve action potentials in all tested nerves, without signs of
      demyelination; needle electromyography documented widespread denervation. The
      diagnosis of acute motor and sensory axonal neuropathy was made. After 3 months
      of intensive rehabilitation, the patient regained the ability to walk with little
      assistance and was discharged home. In conclusion, normal NCS findings up to
      several weeks do not exclude the diagnosis of GBS. Very proximal axonal
      conduction failure with late distal axonal degeneration should be taken into
      consideration, and electrodiagnostic follow-up examinations, even employing
      unusual techniques, are recommended over several weeks after disease onset.

PMID- 29167660
TI  - Characterization of Pseudomonas spp. and Associated Proteolytic Properties in Raw
      Milk Stored at Low Temperatures.
AB  - Milk spoilage is caused by the presence of proteolytic enzymes produced by
      Pseudomonas spp. during storage at low temperatures. The aim of this study was to
      identify Pseudomonas spp. in raw milk and investigate their associated
      proteolytic properties at low temperatures. Raw milk samples (n = 87) were
      collected from 87 bulk tanks in Shaanxi Province in China. Pseudomonas spp. were
      identified using Pseudomonas specific 16S, universal 16S rRNA sequencing, and
      rpoB gene sequencing. The proteolytic properties of Pseudomonas spp. were
      examined using milk agar, quantitative trinitrobenzenesulfonic acid assay, and by
      the presence of alkaline metallopeptidase gene (aprX). A total 143 isolates from
      all 87 samples were confirmed as Pseudomonas, and were identified as belonging to
      14 Pseudomonas species. Of these, 40 (28.0%) isolates revealed proteolysis on
      milk agar at 2 degrees C, 74 (51.8%) at 4 degrees C, 104 (72.7%) at 7 degrees C,
      and 102 (71.3%) at 10 degrees C. However, proteolytic activity of 45 (31.5%)
      isolates exceeded 2 MUmol of glycine equivalents per mL at 7 degrees C, followed
      by 43 (30.1%) at 10 degrees C, 18 (12.6%) at 4 degrees C, and 7 (4.9%) at 2
      degrees C. The results reveal proteolytic activity of Pseudomonas spp. present in
      milk and their spoilage potential at different temperatures.

PMID- 29167661
TI  - Investigating the Effect of Growth Phase on the Surface-Layer Associated Proteome
      of Lactobacillus acidophilus Using Quantitative Proteomics.
AB  - Bacterial surface-layers (S-layers) are semi-porous crystalline arrays that self
      assemble to form the outermost layer of some cell envelopes. S-layers have been
      shown to act as scaffolding structures for the display of auxiliary proteins
      externally. These S-layer associated proteins have recently gained attention in
      probiotics due to their direct physical contact with the intestinal mucosa and
      potential role in cell proliferation, adhesion, and immunomodulation. A number of
      studies have attempted to catalog the S-layer associated proteome of
      Lactobacillus acidophilus NCFM under a single condition. However, due to the
      versatility of the cell surface, we chose to employ a multiplexing-based approach
      with the intention of accurately contrasting multiple conditions. In this study,
      a previously described lithium chloride isolation protocol was used to release
      proteins bound to the L. acidophilus S-layer during logarithmic and early
      stationary growth phases. Protein quantification values were obtained via TMT
      (tandem mass tag) labeling combined with a triple-stage mass spectrometry (MS3)
      method. Results showed significant growth stage-dependent alterations to the
      surface-associated proteome while simultaneously highlighting the sensitivity and
      reproducibility of the technology. Thus, this study establishes a framework for
      quantifying condition-dependent changes to cell surface proteins that can easily
      be applied to other S-layer forming bacteria.

PMID- 29167659
TI  - Balancing Herbal Medicine and Functional Food for Prevention and Treatment of
      Cardiometabolic Diseases through Modulating Gut Microbiota.
AB  - It has become apparent that gut microbiota is closely associated with
      cardiometabolic diseases (CMDs), and alteration in microbiome compositions is
      also linked to the host environment. Next generation sequencing (NGS) has
      facilitated in-depth studies on the effects of herbal medicine and functional
      food on gut microbiota. Both herbal medicine and functional food contain fiber,
      polyphenols and polysaccharides, exerting prebiotics-like activities in the
      prevention and treatment of CMDs. The administrations of herbal medicine and
      functional food lead to increased the abundance of phylum Bacteroidetes, and
      genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella,
      while reducing phylum Firmicutes and Firmicutes/Bacteroidetes ratio in gut. Both
      herbal medicine and functional food interact with gut microbiome and alter the
      microbial metabolites including short-chain fatty acids (SCFAs), bile acids (BAs)
      and lipopolysaccharides (LPS), which are now correlated with metabolic diseases
      such as type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease
      (NAFLD). In addition, trimethylamine (TMA)-N-oxide (TMAO) is recently linked to
      atherosclerosis (AS) and cardiovascular disease (CVD) risks. Moreover, gut-organs
      axes may serve as the potential strategy for treating CMDs with the intervention
      of herbal medicine and functional food. In summary, a balance between herbal
      medicine and functional food rich in fiber, polyphenols and polysaccharides plays
      a vital role in modulating gut microbiota (phylum Bacteroidetes, Firmicutes and
      Firmicutes/Bacteroidetes ratio, and genus Akkermansia, Bifidobacteria,
      Lactobacillus, Bacteroides and Prevotella) through SCFAs, BAs, LPS and TMAO
      signaling regarding CMDs. Targeting gut-organs axes may serve as a new
      therapeutic strategy for CMDs by herbal medicine and functional food in the
      future. This review aims to summarize the balance between herbal medicine and
      functional food utilized for the prevention and treatment of CMDs through
      modulating gut microbiota.

PMID- 29167662
TI  - Site-Directed Mutagenesis Study Revealed Three Important Residues in Hc-DAF-22, a
      Key Enzyme Regulating Diapause of Haemonchus contortus.
AB  - Haemonchus contortus (H. contortus) is one of the most important parasites of
      small ruminants, especially goats and sheep. The complex life cycle of this
      nematode is a main obstacle for the control and prevention of haemonchosis. So
      far, a special form of arrested development called diapause different from the
      dauer stage in Caenorhabditis elegans (C. elegans) has been found in many
      parasitic nematodes. In our previous study, we have characterized a novel gene Hc
      daf-22 from H. contortus sharing high homology with Ce-daf-22 and functional
      analysis showed this gene has similar biological function with Ce-daf-22. In this
      study, Hc-daf-22 mutants were constructed using site-directed mutagenesis, and
      carried out rescue experiments, RNA interference (RNAi) experiments and in vitro
      enzyme activity analysis with the mutants to further explore the precise function
      site of Hc-DAF-22. The results showed that Hc-daf-22 mutants could be expressed
      in the rescued ok693 worms and the expression positions were mainly in the
      intestine which was identical with that of Hc-daf-22 rescued worms. Through lipid
      staining we found that Hc-daf-22 could rescue daf-22 mutant (ok693) from the
      fatty acid metabolism deficiency while Hc-daf-22 mutants failed. Brood size and
      body length analyses in rescue experiment along with body length and life span
      analyses in RNAi experiment elucidated that Hc-daf-22 resembled Ce-daf-22 in
      effecting the development and capacity of C. elegans and mutants impaired the
      function of Hc-daf-22. Together with the protease activity assay, this research
      revealed three important active resides 84C/299H/349H in Hc-DAF-22 by site
      directed mutagenesis.

PMID- 29167663
TI  - Metagenomic Analysis of the Gut Microbiome of the Common Black Slug Arion ater in
      Search of Novel Lignocellulose Degrading Enzymes.
AB  - Some eukaryotes are able to gain access to well-protected carbon sources in plant
      biomass by exploiting microorganisms in the environment or harbored in their
      digestive system. One is the land pulmonate Arion ater, which takes advantage of
      a gut microbial consortium that can break down the widely available, but
      difficult to digest, carbohydrate polymers in lignocellulose, enabling them to
      digest a broad range of fresh and partially degraded plant material efficiently.
      This ability is considered one of the major factors that have enabled A. ater to
      become one of the most widespread plant pest species in Western Europe and North
      America. Using metagenomic techniques we have characterized the bacterial
      diversity and functional capability of the gut microbiome of this notorious
      agricultural pest. Analysis of gut metagenomic community sequences identified
      abundant populations of known lignocellulose-degrading bacteria, along with well
      characterized bacterial plant pathogens. This also revealed a repertoire of more
      than 3,383 carbohydrate active enzymes (CAZymes) including multiple enzymes
      associated with lignin degradation, demonstrating a microbial consortium capable
      of degradation of all components of lignocellulose. This would allow A. ater to
      make extensive use of plant biomass as a source of nutrients through exploitation
      of the enzymatic capabilities of the gut microbial consortia. From this
      metagenome assembly we also demonstrate the successful amplification of multiple
      predicted gene sequences from metagenomic DNA subjected to whole genome
      amplification and expression of functional proteins, facilitating the low cost
      acquisition and biochemical testing of the many thousands of novel genes
      identified in metagenomics studies. These findings demonstrate the importance of
      studying Gastropod microbial communities. Firstly, with respect to understanding
      links between feeding and evolutionary success and, secondly, as sources of novel
      enzymes with biotechnological potential, such as, CAZYmes that could be used in
      the production of biofuel.

PMID- 29167665
TI  - Microbiological and Physicochemical Changes in Natural Green Heat-Shocked Alorena
      de Malaga Table Olives.
AB  - Preserving the highly appreciated natural freshness of Alorena de Malaga table
      olives and preventing their progressive darkening during processing is a major
      challenge. In this work, heat-shocked (60 degrees C, 5 min) fruits were processed
      according to the three denominations referred to in the Protected Designation of
      Origen (cured, fresh green, and traditional) and their characteristics compared
      with those that followed the habitual industrial process (controls). The results
      revealed that the effects of the heat treatment on the evolution of pH,
      titratable acidity, salt, sugar, organic acid, ethanol content, texture, and
      color of fruits as well as on microbial populations (yeasts and lactic acid
      bacteria) were slight in the case of the fresh green and cured presentations.
      However, the differences between heat-shocked and its control were remarkable in
      the traditional process. Notably, the heat treatment favored lactic acid
      fermentation, retention of the green appearance of the fruits, stability during
      packaging, and led to the highest sensory evaluation. The metagenomic analysis
      carried out at the end of the fermentation revealed the presence in all samples
      of three genera (Lactobacillus, Pediococcus, and Celerinatantimonas) which
      encompassed most of the sequences. The number of Lactobacillus sequences was
      statistically higher (p >= 0.05) in the case of traditional heat-shocked fruits
      than in its control.

PMID- 29167664
TI  - Metabolic Engineering of Oleaginous Yeasts for Production of Fuels and Chemicals.
AB  - Oleaginous yeasts have been increasingly explored for production of chemicals and
      fuels via metabolic engineering. Particularly, there is a growing interest in
      using oleaginous yeasts for the synthesis of lipid-related products due to their
      high lipogenesis capability, robustness, and ability to utilize a variety of
      substrates. Most of the metabolic engineering studies in oleaginous yeasts
      focused on Yarrowia that already has plenty of genetic engineering tools.
      However, recent advances in systems biology and synthetic biology have provided
      new strategies and tools to engineer those oleaginous yeasts that have naturally
      high lipid accumulation but lack genetic tools, such as Rhodosporidium,
      Trichosporon, and Lipomyces. This review highlights recent accomplishments in
      metabolic engineering of oleaginous yeasts and recent advances in the development
      of genetic engineering tools in oleaginous yeasts within the last 3 years.

PMID- 29167666
TI  - First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency
      Clinical Achievements and Insights.
AB  - Severe combined immunodeficiency (SCID), the most severe form of T cell
      immunodeficiency, is detectable through quantification of T cell receptor
      excision circles (TRECs) in dried blood spots obtained at birth. Herein, we
      describe the results of the first year of the Israeli SCID newborn screening
      (NBS) program. This important, life-saving screening test is available at no cost
      for every newborn in Israel. Eight SCID patients were diagnosed through the NBS
      program in its first year, revealing an incidence of 1:22,500 births in the
      Israeli population. Consanguine marriages and Muslim ethnic origin were found to
      be a risk factor in affected newborns, and a founder effect was detected for both
      IL7Ralpha and DCLRE1C deficiency SCID. Lymphocyte subset analysis and TREC
      quantification in the peripheral blood appear to be sufficient for confirmation
      of typical and leaky SCID and ruling out false positive (FP) results. Detection
      of secondary targets (infants with non-SCID lymphopenia) did not significantly
      affect the management or outcomes of these infants in our cohort. In the general,
      non-immunodeficient population, TREC rises along with gestational age and birth
      weight, and is significantly higher in females and the firstborn of twin pairs.
      Low TREC correlates with both gestational age and birth weight in extremely
      premature newborns. Additionally, the rate of TREC increase per week consistently
      accelerates with gestational age. Together, these findings mandate a lower cutoff
      or a more lenient screening algorithm for extremely premature infants, in order
      to reduce the high rate of FPs within this group. A significant surge in TREC
      values was observed between 28 and 30 weeks of gestation, where median TREC copy
      numbers rise by 50% over 2 weeks. These findings suggest a maturational step in T
      cell development around week 29 gestation, and imply moderate to late preterms
      should be screened with the same cutoff as term infants. The SCID NBS program is
      still in its infancy, but is already bearing fruit in the early detection and
      improved outcomes of children with SCID in Israel and other countries.

PMID- 29167667
TI  - Bruton's Tyrosine Kinase: An Emerging Key Player in Innate Immunity.
AB  - Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of
      B cell receptor signaling in the development and functioning of adaptive
      immunity. Growing evidence also suggests multiple roles for BTK in mononuclear
      cells of the innate immune system, especially in dendritic cells and macrophages.
      For example, BTK has been shown to function in Toll-like receptor-mediated
      recognition of infectious agents, cellular maturation and recruitment processes,
      and Fc receptor signaling. Most recently, BTK was additionally identified as a
      direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome.
      BTK has thus attracted interest not only for gaining a more thorough basic
      understanding of the human innate immune system but also as a target to
      therapeutically modulate innate immunity. We here review the latest developments
      on the role of BTK in mononuclear innate immune cells in mouse versus man, with
      specific emphasis on the sensing of infectious agents and the induction of
      inflammation. Therapeutic implications for modulating innate immunity and
      critical open questions are also discussed.

PMID- 29167668
TI  - A Practical Approach to Newborn Screening for Severe Combined Immunodeficiency
      Using the T Cell Receptor Excision Circle Assay.
AB  - Severe combined immunodeficiency (SCID) is a life-threatening condition of
      newborns and infants caused by defects in genes involved in T cell development.
      Newborn screening (NBS) for SCID using the T cell receptor excision circle (TREC)
      assay began in Wisconsin in 2008 and has been adopted or is being implemented by
      all states in 2017. It has been established that NBS using the TREC assay is
      extremely sensitive to detect SCID in the newborn period. Some controversies
      remain regarding how screening positives are handled by individual states,
      including when to perform confirmatory flow cytometry, what is the necessary
      diagnostic workup of patients, what infection prophylaxis measures should be
      taken, and when hematopoietic stem cell transplantation should occur. In
      addition, the TREC can also assay detect infants with T cell lymphopenia who are
      not severe enough to be considered SCID; management of these infants is also
      evolving.

PMID- 29167669
TI  - Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages.
AB  - Tumor-associated macrophages (TAMs) frequently help to sustain tumor growth and
      mediate immune suppression in the tumor microenvironment (TME). Here, we
      identified a subset of iron-loaded, pro-inflammatory TAMs localized in
      hemorrhagic areas of the TME. The occurrence of iron-loaded TAMs (iTAMs)
      correlated with reduced tumor size in patients with non-small cell lung cancer.
      Ex vivo experiments established that TAMs exposed to hemolytic red blood cells
      (RBCs) were converted into pro-inflammatory macrophages capable of directly
      killing tumor cells. This anti-tumor effect could also be elicited via iron oxide
      nanoparticles. When tested in vivo, tumors injected with such iron oxide
      nanoparticles led to significantly smaller tumor sizes compared to controls.
      These results identify hemolytic RBCs and iron as novel players in the TME that
      repolarize TAMs to exert direct anti-tumor effector function. Thus, the delivery
      of iron to TAMs emerges as a simple adjuvant therapeutic strategy to promote anti
      cancer immune responses.

PMID- 29167672
TI  - Novel Concept of CD4-Mediated Activation of Regulatory T Cells for the Treatment
      of Graft-Versus-Host Disease.
AB  - Allogeneic hematopoietic stem cell transplantation is the only curative treatment
      option for several hematological malignancies and immune deficiency syndromes.
      Nevertheless, the development of a graft-versus-host disease (GvHD) after
      transplantation is a high risk and a severe complication with high morbidity and
      mortality causing therapeutic challenges. Current pharmacological therapies of
      GvHD lead to generalized immunosuppression followed by severe adverse side
      effects including infections and relapse of leukemia. Several novel cell-based
      immunomodulatory strategies for treatment or prevention of GvHD have been
      developed. Herein, thymus-derived regulatory T cells (tTreg), essential for the
      maintenance of peripheral immunologic tolerance, are in the focus of
      investigation. However, due to the limited number of tTreg in the peripheral
      blood, a complex, time- and cost-intensive in vitro expansion protocol is
      necessary for the production of an efficient cellular therapeutic. We
      demonstrated that activation of tTreg using the CD4-binding human
      immunodeficiency virus-1 protein gp120 leads to a substantially increased
      suppressor activity of tTreg without the need for additional expansion. Gp120
      activated tTreg prevent GvHD development in a preclinical humanized mouse model.
      In addition, gp120 is not only effective in prevention but also in therapy of
      GvHD by suppressing all clinical symptoms and improving survival of treated mice.
      These data indicate that tTreg activation by gp120 is a feasible and potent
      strategy for significant functional improvement of tTreg as cellular therapeutic
      for GvHD treatment without the need of complicated, time-intensive, and expensive
      in vitro expansion of isolated tTreg.

PMID- 29167670
TI  - The Cholinergic System Modulates Memory and Hippocampal Plasticity via Its
      Interactions with Non-Neuronal Cells.
AB  - Degeneration of central cholinergic neurons impairs memory, and enhancement of
      cholinergic synapses improves cognitive processes. Cholinergic signaling is also
      anti-inflammatory, and neuroinflammation is increasingly linked to adverse
      memory, especially in Alzheimer's disease. Much of the evidence surrounding
      cholinergic impacts on the neuroimmune system focuses on the alpha7 nicotinic
      acetylcholine (ACh) receptor, as stimulation of this receptor prevents many of
      the effects of immune activation. Microglia and astrocytes both express this
      receptor, so it is possible that some cholinergic effects may be via these non
      neuronal cells. Though the presence of microglia is required for memory,
      overactivated microglia due to an immune challenge overproduce inflammatory
      cytokines, which is adverse for memory. Blocking these exaggerated effects,
      specifically by decreasing the release of tumor necrosis factor alpha (TNF
      alpha), interleukin 1beta (IL-1beta), and interleukin 6 (IL-6), has been shown to
      prevent inflammation-induced memory impairment. While there is considerable
      evidence that cholinergic signaling improves memory, fewer studies have linked
      the "cholinergic anti-inflammatory pathway" to memory processes. This review will
      summarize the current understanding of the cholinergic anti-inflammatory pathway
      as it relates to memory and will argue that one mechanism by which the
      cholinergic system modulates hippocampal memory processes is its influence on
      neuroimmune function via the alpha7 nicotinic ACh receptor.

PMID- 29167673
TI  - Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4+ T
      Cell Effector Responses and Induces CD25+Foxp3+ T Regulatory Subsets.
AB  - Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to
      influence immune responses in macrophages and microglial cells. The protein
      contains Ca2+ binding EF-hand and PDZ interaction domains important for mediating
      intracellular signaling complexes. This study now reports that AIF1 is expressed
      in CD11c+ dendritic cells (DC) and silencing of expression restrains induction of
      antigen-specific CD4+ T cell effector responses. AIF1 knockdown in murine DC
      resulted in impaired T cell proliferation and skewed polarization away from T
      helper type 1 and 17 fates. In turn, there was a parallel expansion of IL-10
      producing and CD25+Foxp3+ T regulatory subsets. These studies are the first to
      demonstrate that AIF1 expression in DC serves as a potent governor of cognate T
      cell responses and presents a novel target for engineering tolerogenic DC-based
      immunotherapies.

PMID- 29167671
TI  - Immune Checkpoint Targets for Host-Directed Therapy to Prevent and Treat
      Leishmaniasis.
AB  - Leishmaniasis encompasses a group of diseases caused by protozoan parasites
      belonging to the genus Leishmania. These diseases range from life threatening
      visceral forms to self-healing cutaneous lesions, and each disease manifestations
      can progress to complications involving dissemination of parasites to skin or
      mucosal tissue. A feature of leishmaniasis is the key role host immune responses
      play in disease outcome. T cells are critical for controlling parasite growth.
      However, they can also contribute to disease onset and progression. For example,
      potent regulatory T cell responses can develop that suppress antiparasitic
      immunity. Alternatively, hyperactivated CD4+ or CD8+ T cells can be generated
      that cause damage to host tissues. There is no licensed human vaccine and drug
      treatment options are often limited and problematic. Hence, there is an urgent
      need for new strategies to improve the efficacy of current vaccine candidates
      and/or enhance both antiparasitic drug effectiveness and subsequent immunity in
      treated individuals. Here, we describe our current understanding about host
      immune responses contributing to disease protection and progression in the
      various forms of leishmaniasis. We also discuss how this knowledge may be used to
      develop new strategies for host-directed immune therapy to prevent or treat
      leishmaniasis. Given the major advances made in immune therapy in the cancer and
      autoimmune fields in recent years, there are significant opportunities to ride on
      the back of these successes in the infectious disease domain. Conversely, the
      rapid progress in our understanding about host immune responses during
      leishmaniasis is also providing opportunities to develop novel immunotherapy
      strategies that could have broad applications in diseases characterized by
      inflammation or immune dysfunction.

PMID- 29167674
TI  - A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+
      Regulatory T Cells and Suppresses Murine Allograft Rejection.
AB  - Due to vigorous alloimmunity, an allograft is usually rejected without any
      conventional immunosuppressive treatment. However, continuous global
      immunosuppression may cause severe side effects, including tumors and infections.
      Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant
      used in clinic, impedes allograft tolerance by dampening regulatory T cells
      (Tregs), although it inhibits allograft rejection at the same time. Therefore, it
      is necessary to seek an alternative immunosuppressive drug that spares Tregs with
      high efficiency in suppression but low toxicity. In this study, we investigated
      the capacity of emodin, an anthraquinone molecule originally extracted from
      certain natural plants, to prolong transplant survival in a mouse model and
      explored the cellular and molecular mechanisms underlying its action. We found
      that emodin significantly extended skin allograft survival and hindered CD3+ T
      cell infiltration in the allograft, accompanied by an increase in CD4+Foxp3+ and
      CD8+CD122+ Treg frequencies and numbers but a reduction in effector
      CD8+CD44highCD62Llow T cells in recipient mice. Emodin also inhibited effector
      CD8+ T cells proliferation in vivo. However, CD4+CD25+, but not CD8+CD122+, Tregs
      derived from emodin-treated recipients were more potent in suppression of
      allograft rejection than those isolated from control recipients, suggesting that
      emodin also enhances the suppressive function of CD4+CD25+ Tregs. Interestingly,
      depleting CD25+ Tregs largely reversed skin allograft survival prolonged by
      emodin while depleting CD122+ Tregs only partially abrogated the same allograft
      survival. Furthermore, we found that emodin hindered dendritic cell (DC)
      maturation and reduced alloantibody production posttransplantation. Finally, we
      demonstrated that emodin inhibited in vitro proliferation of T cells and blocked
      their mTOR signaling as well. Therefore, emodin may be a novel mTOR inhibitor
      that suppresses alloimmunity by inducing both CD4+FoxP3+ and CD8+CD122+ Tregs,
      suppressing alloantibody production, and hindering DC maturation. Thus, emodin is
      a newly emerging immunosuppressant and could be utilized in clinical
      transplantation in the future.

PMID- 29167675
TI  - Boron Deficiency in Trifoliate Orange Induces Changes in Pectin Composition and
      Architecture of Components in Root Cell Walls.
AB  - Boron (B) is a micronutrient indispensable for citrus and B deficiency causes a
      considerable loss of productivity and quality in China. However, studies on
      pectin composition and architecture of cell wall components in trifoliate orange
      roots under B deficiency condition are not sufficient. In this study, we
      investigated the alteration in pectin characteristics and the architecture of
      cell wall components in trifoliate orange [Poncirus trifoliata (L.) Raf.] roots
      under B starvation. The results showed that B-deficient roots resulted in a
      significant enlargement of root tips and an obvious decrease in cell wall B and
      uronic acid content in Na2CO3-soluble pectin compared with B-adequate roots.
      Meanwhile, they showed a decrease of 2-keto-3-deoxyoctanoic acid in CDTA-soluble
      and Na2CO3-soluble pectin in cell walls, while the degree of methylation (DM) of
      CDTA-soluble pectin was significantly increased under B deficiency. Transmission
      electron microscope (TEM) micrographs of B deficient plants showed a distinct
      thickening of the cell walls, with the thickness 1.82 times greater than that of
      control plant roots. The results from Fourier-transform infrared spectroscopy
      (FTIR) showed that B deficiency changed the mode of hydrogen bonding between
      protein and carbohydrates (cellulose and hemicellulose). The FTIR spectra
      exhibited a destroyed protein structure and accumulation of wax and cellulose in
      the cell walls under B starvation. The 13C nuclear magnetic resonance (13C-NMR)
      spectra showed that B starvation changed the organic carbon structure of cell
      walls, and enhanced the contents of amino acid, cellulose, phenols, and lignin in
      the cell wall. The results reveal that the swelling and weakened structural
      integrity of cell walls, which induced by alteration on the network of pectin and
      cell wall components and structure in B-deficient roots, could be a major cause
      of occurrence of the rapid interruption of growth and significantly enlarged root
      tips in trifoliate orange roots under B-insufficient condition.

PMID- 29167676
TI  - The Effect of Season-Long Temperature Increases on Rice Cultivars Grown in the
      Central and Southern Regions of China.
AB  - Rice production is challenged by the asymmetric increases in day and night
      temperatures. Efforts are required to improve our understanding of the impact of
      climate change on rice production. To this end, 2-year experiment was conducted
      to evaluate the response of mid-season rice growth in the central and southern
      regions of China to elevated temperatures. Four replicates of four widely planted
      indica rice cultivars (Huanghuazhan: HHZ; Shanyou63: SY63; Yangliangyou6: YLY6;
      Liangyoupeijiu: LYPJ) were subjected to four elevated-temperature treatments
      (control: ambient temperature; NW: night-time warming; DW: daytime warming; AW:
      all-day warming) generated by an open-top hot-blast system under field
      conditions. This apparatus causes an ~2 degrees C increase in the rice canopy
      temperature. Of all the elevated-temperature treatments, AW was the most
      devastating treatment for all rice cultivars, negatively affecting nearly all of
      investigated parameters, including grain yield and its components, dry matter
      accumulation, biomass, and harvest index (HI). The AW treatment decreased the
      grain yield by 11-35% and 43-78% in 2015 and 2016, respectively. No significant
      reduction in the grain yield was observed in the DW and NW treatments in 2015.
      However, the grain yield was decreased in DW and NW treatments by 20-52% and 18
      55%, respectively, in 2016. Furthermore, the temperature-driven degradation of
      pollen viability, the number of pollen grains adhering to the stigma and pollen
      germination on the stigma caused spikelet sterility and thereby decreased the
      grain yield. The YLY6 and SY63 cultivars performed better than the HHZ and LYPJ
      cultivars with respect to grain yield and its components in all elevated
      temperature treatments in both years. However, 42.97 and 61.01% reductions still
      occurred for the SY63 and YLY6 cultivars, respectively, in the AW treatment in
      2016. The above results suggested that the elevated temperature may cause a
      noteworthy reduction in the productions of these widely planted genotypes in
      central and southern regions of China. To ensure the security of rice production
      in this region in an expected global warming environment, currently planted
      varieties will need to be replaced by heat-resistant varieties in the future.

PMID- 29167677
TI  - Effect of Trait Heritability, Training Population Size and Marker Density on
      Genomic Prediction Accuracy Estimation in 22 bi-parental Tropical Maize
      Populations.
AB  - Genomic selection is being used increasingly in plant breeding to accelerate
      genetic gain per unit time. One of the most important applications of genomic
      selection in maize breeding is to predict and select the best un-phenotyped lines
      in bi-parental populations based on genomic estimated breeding values. In the
      present study, 22 bi-parental tropical maize populations genotyped with low
      density SNPs were used to evaluate the genomic prediction accuracy (rMG ) of the
      six trait-environment combinations under various levels of training population
      size (TPS) and marker density (MD), and assess the effect of trait heritability
      (h2 ), TPS and MD on rMG estimation. Our results showed that: (1) moderate rMG
      values were obtained for different trait-environment combinations, when 50% of
      the total genotypes was used as training population and ~200 SNPs were used for
      prediction; (2) rMG increased with an increase in h2 , TPS and MD, both
      correlation and variance analyses showed that h2 is the most important factor and
      MD is the least important factor on rMG estimation for most of the trait
      environment combinations; (3) predictions between pairwise half-sib populations
      showed that the rMG values for all the six trait-environment combinations were
      centered around zero, 49% predictions had rMG values above zero; (4) the trend
      observed in rMG differed with the trend observed in rMG /h, and h is the square
      root of heritability of the predicted trait, it indicated that both rMG and rMG
      /h values should be presented in GS study to show the accuracy of genomic
      selection and the relative accuracy of genomic selection compared with phenotypic
      selection, respectively. This study provides useful information to maize breeders
      to design genomic selection workflow in their breeding programs.

PMID- 29167678
TI  - A Radish Basic Helix-Loop-Helix Transcription Factor, RsTT8 Acts a Positive
      Regulator for Anthocyanin Biosynthesis.
AB  - The MYB-bHLH-WDR (MBW) complex activates anthocyanin biosynthesis through the
      transcriptional regulation. RsMYB1 has been identified as a key player in
      anthocyanin biosynthesis in red radish (Raphanus sativus L.), but its partner
      bHLH transcription factor (TF) remains to be determined. In this study, we
      isolated a bHLH TF gene from red radish. Phylogenetic analysis indicated that
      this gene belongs to the TT8 clade of the IIIF subgroup of bHLH TFs, and we thus
      designated this gene RsTT8. Subcellular localization analysis showed that RsTT8
      sGFP was localized to the nuclei of Arabidopsis thaliana protoplasts harboring
      the RsTT8-sGFP construct. We evaluated anthocyanin biosynthesis and RsTT8
      expression levels in three radish varieties (N, C, and D) that display different
      red phenotypes in the leaves, root flesh, and root skins. The root flesh of the C
      variety and the leaves and skins of the D variety exhibit intense red
      pigmentation; in these tissues, RsTT8 expression showed totally positive
      association with the expression of RsMYB1 TF and of five of eight tested
      anthocyanin biosynthesis genes (i.e., RsCHS, RsCHI, RsF3H, RsDFR, and RsANS).
      Heterologous co-expression of both RsTT8 and RsMYB1 in tobacco leaves
      dramatically increased the expression of endogenous anthocyanin biosynthesis
      genes and anthocyanin accumulation. Furthermore, a yeast two-hybrid assay showed
      that RsTT8 interacts with RsMYB1 at the MYB-interacting region (MIR), and a
      transient transactivation assay indicated that RsTT8 activates the RsCHS and
      RsDFR promoters when co-expressed with RsMYB1. Complementation of the Arabidopsis
      tt8-1 mutant, which lacks red pigmentation in the leaves and seeds, with RsTT8
      restored red pigmentation, and resulted in high anthocyanin and proanthocyanidin
      contents in the leaves and seeds, respectively. Together, these results show that
      RsTT8 functions as a regulatory partner with RsMYB1 during anthocyanin
      biosynthesis.

PMID- 29167679
TI  - Effects of Mountain Uplift and Climatic Oscillations on Phylogeography and
      Species Divergence in Four Endangered Notopterygium Herbs.
AB  - Mountain uplift and climatic fluctuations are important driving forces that have
      affected the geographic distribution and population dynamics history of
      organisms. However, it is unclear how geological and climatic events might have
      affected the phylogeographic history and species divergence in high-alpine herbal
      plants. In this study, we analyzed the population demographic history and species
      differentiation of four endangered Notopterygium herbs on the high-altitude
      Qinghai-Tibetan Plateau (QTP) and adjacent areas. We combined phylogeographic
      analysis with species distribution modeling to detect the genetic variations in
      four Notopterygium species (N. incisum, N. franchetii, N. oviforme, and N.
      forrestii). In total, 559 individuals from 74 populations of the four species
      were analyzed based on three maternally inherited chloroplast fragments (matK,
      rbcL, and trnS-trnG) and one nuclear DNA region (internal transcribed spacer,
      ITS). Fifty-five chloroplast DNA (cpDNA) and 48 ITS haplotypes were identified in
      the four species. All of the cpDNA and ITS haplotypes were species-specific,
      except N. franchetii and N. oviforme shared one cpDNA haplotype, H32.
      Phylogenetic analysis suggested that all four species formed a monophyletic clade
      with high bootstrap support, where N. franchetii and N. oviforme were sisters. In
      addition, each Notopterygium species generated an individual clade that
      corresponded to their respective species in the ITS tree. Population dynamics
      analyses and species distribution modeling showed that the two widely distributed
      herbs N. incisum and N. franchetii exhibited obvious demographic expansions
      during the Pleistocene ice ages. Molecular dating suggested that the divergence
      of the four Notopterygium species occurred approximately between 3.6 and 1.2 Mya,
      and it was significantly associated with recent extensive uplifts of the QTP. Our
      results support the hypothesis that mountain uplift and Quaternary climatic
      oscillations profoundly shaped the population genetic divergence and demographic
      dynamics of Notopterygium species. The findings of this and previous studies
      provide important insights into the effects of QTP uplifts and climatic changes
      on phylogeography and species differentiation in high altitude mountainous areas.
      Our results may also facilitate the conservation of endangered herbaceous
      medicinal plants in the genus Notopterygium.

PMID- 29167680
TI  - Gene Editing and Crop Improvement Using CRISPR-Cas9 System.
AB  - Advancements in Genome editing technologies have revolutionized the fields of
      functional genomics and crop improvement. CRISPR/Cas9 (clustered regularly
      interspaced short palindromic repeat)-Cas9 is a multipurpose technology for
      genetic engineering that relies on the complementarity of the guideRNA (gRNA) to
      a specific sequence and the Cas9 endonuclease activity. It has broadened the
      agricultural research area, bringing in new opportunities to develop novel plant
      varieties with deletion of detrimental traits or addition of significant
      characters. This RNA guided genome editing technology is turning out to be a
      groundbreaking innovation in distinct branches of plant biology. CRISPR
      technology is constantly advancing including options for various genetic
      manipulations like generating knockouts; making precise modifications, multiplex
      genome engineering, and activation and repression of target genes. The review
      highlights the progression throughout the CRISPR legacy. We have studied the
      rapid evolution of CRISPR/Cas9 tools with myriad functionalities, capabilities,
      and specialized applications. Among varied diligences, plant nutritional
      improvement, enhancement of plant disease resistance and production of drought
      tolerant plants are reviewed. The review also includes some information on
      traditional delivery methods of Cas9-gRNA complexes into plant cells and
      incorporates the advent of CRISPR ribonucleoproteins (RNPs) that came up as a
      solution to various limitations that prevailed with plasmid-based CRISPR system.

PMID- 29167681
TI  - miR-200b downregulates CFTR during hypoxia in human lung epithelial cells.
AB  - Background: Hypoxic conditions induce the expression of hypoxia-inducible factors
      (HIFs) that allow cells to adapt to the changing conditions and alter the
      expression of a number of genes including the cystic fibrosis transmembrane
      conductance regulator (CFTR). CFTR is a low abundance mRNA in airway epithelial
      cells even during normoxic conditions, but during hypoxia its mRNA expression
      decreases even further. Methods: In the current studies, we examined the kinetics
      of hypoxia-induced changes in CFTR mRNA and protein levels in two human airway
      epithelial cell lines, Calu-3 and 16HBE14o-, and in normal primary bronchial
      epithelial cells. Our goal was to examine the posttranscriptional modifications
      that affected CFTR expression during hypoxia. We utilized in silico predictive
      protocols to establish potential miRNAs that could potentially regulate CFTR
      message stability and identified miR-200b as a candidate molecule. Results:
      Analysis of each of the epithelial cell types during prolonged hypoxia revealed
      that CFTR expression decreased after 12 h during a time when miR-200b was
      continuously upregulated. Furthermore, manipulation of the miRNA levels during
      normoxia and hypoxia using miR-200b mimics and antagomirs decreased and increased
      CFTR mRNA levels, respectively, and thus established that miR-200b downregulates
      CFTR message levels during hypoxic conditions. Conclusion: The data suggest that
      miR-200b may be a suitable target for modulating CFTR levels in vivo.

PMID- 29167682
TI  - Root Morphology of the Maxillary First and Second Molars in an Iranian Population
      Using Cone Beam Computed Tomography.
AB  - Objectives: This study sought to assess the root morphology and root canal
      anatomy of the maxillary first and second molars in an Iranian population using
      cone-beam computed tomography (CBCT). Materials and Methods: Sound fully
      developed maxillary first (n=345) and second (n=423) molars were evaluated on 450
      CBCT scans ordered for pre-operative assessment for implant placement. The (I)
      number of roots and their morphology (II) number of canals per root, (III) canal
      configuration and presence of a second mesiobuccal canal according to the
      Vertucci's classification and (IV) unilateral or bilateral occurrence of a second
      mesiobuccal canal (MB2) were evaluated. Results: Single roots were found in 1.1%
      of the first and 11.3% of the second molars. Four separate roots were identified
      in 0.5% of the first molars; none of the second molars had four separate roots.
      First and second molars showed a higher prevalence of three separate roots of
      mesiobuccal, distobuccal and palatal with one canal in each root (54% and 86 %,
      respectively). The most common anatomical variation in the maxillary first molars
      was related to the configuration of the MB root; the root canal system of the
      maxillary second molars showed more anatomical variations. Conclusions:
      Mesiobuccal roots of the maxillary molars had more variations in their canal
      system than the distobuccal or palatal roots. The root canal configuration of the
      maxillary second molars was more diverse than that of first molars; CBCT enhances
      mapping of the mesiobuccal root canal system with the potential to improve the
      quality of root canal treatment.

PMID- 29167683
TI  - Microleakage of Two Bulk Fill and One Conventional Composite in Class II
      Restorations of Primary Posterior Teeth.
AB  - Objectives: This study aimed to assess and compare the microleakage of two bulk
      fill and one conventional composite in class II restorations of primary posterior
      teeth. Materials and Methods: This in vitro, experimental study was conducted on
      60 primary mandibular second molars, which were randomly divided into three
      groups. Standard class II cavities were prepared in teeth and restored with 3M
      bulk fill composite in group 1, SonicFill bulk fill composite in group 2 and Z250
      conventional composite in group 3. Single Bond 2 bonding agent was used in all
      cavities. The teeth were then thermocycled and immersed in 1M silver nitrate
      solution. The teeth were then mesiodistally sectioned and evaluated under a
      stereomicroscope at*10 magnification. Dye penetration depth was recorded in
      microns and data were analyzed using one-way ANOVA. Results: The mean (+/-
      standard deviation) dye penetration depth in the gingival margins was 543+/
      523MUm, 343+/-290MUm and 597+/-590MUm for 3M bulk fill, SonicFill and Z250
      conventional composite, respectively. These values were 214+/-93MUm, 302+/-127MUm
      and 199+/-145MUm in the occlusal margins, respectively. The three groups were not
      significantly different in terms of occlusal or gingival microleakage (P>0.05),
      but gingival margins showed significantly higher microleakage than occlusal
      margins in all three groups (P<0.05). Conclusions: Bulk fill composites are not
      significantly different from conventional composites in terms of microleakage.

PMID- 29167684
TI  - Demographic Profile of Non-Odontogenic Jaw Lesions in an Iranian Population: A 30
      Year Archive Review.
AB  - Objectives: The frequency of non-odontogenic lesions of the jawbones is lower
      than that of odontogenic lesions; however, study of the epidemiologic data of
      these lesions is required for health care programs. This study aimed to assess
      the relative frequency and demographic profile of non-odontogenic jaw lesions in
      an Iranian population over a 30-year period. Materials and Methods: This archive
      review was performed using demographic and biopsy information of all patients
      with non-odontogenic lesions of the jawbones submitted to the Oral Pathology
      Department of Dental School of Tehran University of Medical Sciences from 1984 to
      2014. Demographic data included in the study were: age at diagnosis, gender and
      location of lesion. The lesions were divided into three groups of group 1: cystic
      lesions, group 2: tumors and tumor-like lesions, and group 3:
      infectious/inflammatory/reactive lesions. Frequency and clinical data were
      analyzed using SPSS 22. Results: Of 972 non-odontogenic jaw lesions, the ratio of
      mandibular to maxillary lesions was 1.63:1. Female to male ratio was 1.33:1 and
      the mean age of patients was 29.09+/-16.90 years. The most common non-odontogenic
      jaw lesion was central giant cell granuloma (CGCG). In groups 1, 2 and 3,
      nasopalatine duct cyst, CGCG, and osteomyelitis were the most frequent lesions,
      respectively. Conclusions: Non-odontogenic lesions of the jawbones are a diverse
      group of lesions with different frequency and behavior. This study demonstrated
      that tumors and tumor-like lesions of the jaws were more common than cystic and
      infectious/inflammatory/reactive lesions. Overall, the most common non
      odontogenic jaw lesion was CGCG.

PMID- 29167685
TI  - Effect of Music Practice on Anxiety and Depression of Iranian Dental Students.
AB  - Objectives: The practice of dentistry has long been associated with high levels
      of occupational stress and anxiety and music has been shown as a method of
      reducing stress. Considering the reportedly high level of stress among dental
      students and its consequences and also considering the positive effect of music
      therapy, the aim of this study was to evaluate the relationship between music
      practice and level of stress in dental students. Materials and Methods: In this
      analytical, cross-sectional study, 88 students, including 44 with a history of
      music practice and 44 matched controls without music practice who met the defined
      inclusion criteria, participated. Upon obtaining written informed consent, all
      volunteers filled the Beck anxiety inventory (BAI) and Beck depression inventory
      (BDI) questionnaires. Data were analyzed using the Kolmogorov-Smirnov test, and
      multiple linear regression test with backward method was used to evaluate the
      effect of demographic factors on anxiety and depression scores. Results: The
      level of anxiety was higher in students who did not have music practice and this
      difference was significant (P<0.001). The same was observed for depression
      (P=0.027). Other factors including age, gender, and being far from family had no
      significant effect on depression and anxiety (P>0.05). But level of anxiety and
      depression was higher in students of universities with tuition fee compared to
      free public institutes (P<0.05). Conclusions: It may be concluded that music
      practice can reduce anxiety and depression of dental students.

PMID- 29167686
TI  - Comparison of Enamel Morphologic Characteristics after Conditioning with Various
      Combinations of Acid Etchant and Er:YAG Laser in Bonding and Rebonding
      Procedures: A SEM Analysis.
AB  - Objectives: Many studies have evaluated re-etched enamel by using scanning
      electron microscopy (SEM); however, there is no evidence regarding the use of
      Erbium-doped yttrium aluminium garnet (Er:YAG) laser at primary and secondary
      bonding instead of acid etching with regards to enamel surface changes. The
      purpose of the present study was to determine that whether or not the methods of
      primary and secondary enamel preparation affect enamel characteristics after
      rebonding, by using SEM analysis. Materials and Methods: Twelve freshly extracted
      premolars were divided into 4 groups. The samples in each group were conditioned
      by acid etchant or Er:YAG laser at primary conditioning, according to the
      instructions. Afterwards, they were bonded with orthodontic brackets. After
      debonding, the samples were prepared for second conditioning. Also, two samples
      were conditioned only once with acid etchant or laser, to compare enamel
      morphology changes with those after re-etching. Finally, buccal enamel surfaces
      were evaluated using SEM. Results: Enamel etching patterns were observed in the
      samples which had been acid-conditioned at first or at both conditionings. The
      samples irradiated by Er:YAG laser showed amorphous and irregular surfaces, with
      no signs of typical etching patterns. A large deep gap was seen in one of the
      samples irradiated with laser at primary and secondary conditionings, which might
      have penetrated the underling layers of enamel and dentin. Conclusions: Enamel
      surface preparation with Er:YAG laser produces irregular and indistinct
      morphologic changes, completely different from those produced after acid etching
      at both conditioning and reconditioning. Therefore, it is recommended to use this
      laser with caution to avoid permanent enamel damage.

PMID- 29167687
TI  - Effect of Self-Adhesive and Separate Etch Adhesive Dual Cure Resin Cements on the
      Bond Strength of Fiber Post to Dentin at Different Parts of the Root.
AB  - Objectives: Bonding of fiber posts to intracanal dentin is challenging in the
      clinical setting. This study aimed to compare the effect of self-adhesive and
      separate etch adhesive dual cure resin cements on the bond strength of fiber post
      to dentin at different parts of the root. Materials and Methods: This in-vitro
      experimental study was conducted on 20 single-rooted premolars. The teeth were
      decoronated at 1mm coronal to the cementoenamel junction (CEJ), and the roots
      underwent root canal treatment. Post space was prepared in the roots. Afterwards,
      the samples were randomly divided into two groups. In group 1, the fiber posts
      were cemented using Rely X Unicem cement, while in group 2, the fiber posts were
      cemented using Duo-Link cement, according to the manufacturer's instructions. The
      intracanal post in each root was sectioned into three segments of coronal,
      middle, and apical, and each cross-section was subjected to push-out bond
      strength test at a crosshead speed of 1mm/minute until failure. Push-out bond
      strength data were analyzed using independent t-test and repeated measures ANOVA.
      Results: The bond strength at the middle and coronal segments in separate etch
      adhesive cement group was higher than that in self-adhesive cement group.
      However, the bond strength at the apical segment was higher in self-adhesive
      cement group compared to that in the other group. Overall, the bond strength in
      separate etch adhesive cement group was significantly higher than that in self
      adhesive cement group (P<0.001). Conclusions: Bond strength of fiber post to
      intracanal dentin is higher after the use of separate etch adhesive cement
      compared to self-adhesive cement.

PMID- 29167688
TI  - Effect of Quaternary Ammonium Salt on Shear Bond Strength of Orthodontic Brackets
      to Enamel.
AB  - Objectives: This study sought to assess the effect of quaternary ammonium salt
      (QAS) on shear bond strength of orthodontic brackets to enamel. Materials and
      Methods: In this in vitro experimental study, 0, 10, 20 and 30% concentrations of
      QAS were added to Transbond XT primer. Brackets were bonded to 60 premolar teeth
      using the afore-mentioned adhesive mixtures, and the shear bond strength of the
      four groups (n=15) was measured using a universal testing machine. After
      debonding, the adhesive remnant index (ARI) score was determined under a
      stereomicroscope. Data were analyzed using one-way ANOVA. Results: The mean and
      standard deviation of shear bond strength of the control and 10%, 20% and 30%
      groups were 23.54+/-6.31, 21.81+/-2.82, 20.83+/-8.35 and 22.91+/-5.66 MPa,
      respectively. No significant difference was noted in shear bond strength of the
      groups (P=0.83). Study groups were not different in terms of ARI scores (P=0.80).
      Conclusions: The results showed that addition of QAS to Transbond XT primer had
      no adverse effect on shear bond strength of orthodontic brackets.

PMID- 29167689
TI  - Fatigue Fracture Strength of Implant-Supported Full Contour Zirconia and Metal
      Ceramic Fixed Partial Dentures.
AB  - Objectives: Zirconia restorations have been suggested as a more durable and more
      appealing alternative to metal restorations. However, their mechanical properties
      may be negatively affected by fatigue due to superficial stresses or low
      temperature degradation. This study aimed to assess the fatigue fracture strength
      of three-unit implant-supported full contour zirconia and pre-sintered cobalt
      chromium (Co-Cr) alloy posterior fixed partial dentures (FPDs). Materials and
      Methods: In this in-vitro experimental study, 28 posterior three-unit implant
      supported FPDs were fabricated of full contour zirconia and pre-sintered Co-Cr
      alloy, and were cemented on implant abutments. To simulate the oral environment,
      FPDs were subjected to 10,000 thermal cycles between 5-55 degrees C for 30
      seconds, and were then transferred to a chewing simulator (100,000 cycles, 50 N,
      0.5 Hz). Afterwards, fatigue fracture strength was measured using a universal
      testing machine. Data were analyzed by Mann-Whitney U test. Results: The mean and
      standard deviation of fracture strength were 2108.6+/-440.1 N in full contour
      zirconia, and 3499.9+/-1106.5 N in pre-sintered Co-Cr alloy. According to Mann
      Whitney U test, the difference in this respect was statistically significant
      between the two groups (P=0.007). Conclusions: Since the fracture strength values
      obtained in the two groups were significantly higher than the maximum mean
      masticatory load in the oral environment, both materials can be used for
      fabrication of posterior three-unit FPDs, depending on the esthetic demands of
      patients.

PMID- 29167690
TI  - Synchronous GISTs associated with multiple sporadic tumors: a case report.
AB  - Gastrointestinal stromal tumors (GISTs) are rare neoplasms, but they also
      represent the most common mesenchymal tumors of the gastrointestinal tract
      originating from the cell of Cajal. GIST incidence ranges around 1% of all
      gastrointestinal malignancies. Approximately 5% of all GISTs have a hereditary
      etiology. The remaining 95% of GISTs are considered sporadic events, with up to
      75% of cases driven by a constitutional activation of the c-KIT proto-oncogene.
      GISTs are generally solitary lesions. Nonetheless, multiple sporadic GISTs can
      occur and present as synchronous or metachronous tumors, usually associated with
      familial GIST. Here, we report a case of primary prostate and lung tumors
      associated with gastric and small bowel GISTs, unrelated to any known hereditary
      syndrome. Also, in the case we describe, the prostatic tumor came before the
      GISTs, while the lung tumor occurred later in time and led to pulmonary lobectomy
      plus lymphoadenectomy, with a diagnosis of nonsmall cell lung cancer. With the
      exception of a slight difference in lymphoid infiltration, the abdominal and
      gastric GIST nodules shared the same proliferative MIB1 index and mitotic count.
      However, the genetic analysis revealed that the gastric GIST and abdominal tumors
      were characterized by two different c-KIT mutations. This molecular heterogeneity
      supported the hypothesis of two different synchronous GISTs arising from stomach
      and ileum. At present, the patient is disease free and has already completed the
      third year of adjuvant therapy with imatinib. This case supports the importance
      of the analysis of c-KIT mutational status to distinguish metastases from
      synchronous multicentric GISTs, with relevant implications in therapeutic
      decisions, as well as the importance of a dedicated multidisciplinary team and of
      a radiological follow-up after the diagnosis of a primary GIST, to discover a
      relapse of the GIST or, possibly, additional malignancies.

PMID- 29167691
TI  - Long-term efficacy and safety of fourth-line multikinase inhibitor treatment with
      lenvatinib in a young papillary thyroid carcinoma patient.
AB  - Lenvatinib, a multikinase inhibitor, is approved for the treatment of patients
      with radioiodine-refractory metastatic thyroid cancer on the basis of a Phase
      III, prospective, double-blind, randomized, placebo-controlled trial that showed
      longer progression-free survival in the drug-treated arm. Here, we report the
      case of a young papillary thyroid cancer patient, pretreated with three other
      kinase inhibitors, who achieved a long-term clinical benefit from lenvatinib in
      the fourth-line setting.

PMID- 29167692
TI  - Prognostic and predictive factors of eribulin efficacy in heavily pretreated
      patients affected by metastatic breast cancer: correlation with tumor biology and
      previous therapies.
AB  - Background: Eribulin mesylate is currently approved in the United States and
      Europe for the treatment of metastatic breast cancer (MBC). Scope: The objective
      of this retrospective study is to find specific predictive criteria related to
      patient or tumor characteristics in order to select patients that might benefit
      the most from eribulin and define the correct treatment sequence. Findings: Forty
      four patients with MBC who received eribulin in third or subsequent lines of
      therapy in a single Italian center were considered eligible. Patients were
      stratified by body mass index, hormonal/HER2 status, and previous therapies.
      Primary endpoint was progression free survival (PFS), whereas secondary endpoint
      was disease control rate (DCR).A longer PFS was found in patients with hormone
      positive tumors (p=0.0051), in HER2-negative cases (p=0.037), and in overweight
      patients (p=0.0015). No difference in efficacy was observed when eribulin was
      administered in third or subsequent lines of therapy. Significantly longer PFS
      (p<0.0001) and higher DCR (p=0.035) were achieved by patients previously treated
      with paclitaxel-bevacizumab in comparison to those pretreated with other drug
      combinations or with anthracyclines. Prior treatment with nab-paclitaxel seems to
      have a detrimental effect on PFS (p=0.0008). Conclusion: Hormone and HER2 status
      seems a good predictive and prognostic indicator of response to eribulin.
      Efficacy seems independent from the number of prior therapies, and it is not
      influenced by prior endocrine treatments and anthracyclines-containing regimens.
      On the other hand, sensitivity to a prior treatment with paclitaxel-bevacizumab
      might be predictive of response to eribulin.

PMID- 29167693
TI  - Approving cancer treatments based on endpoints other than overall survival: an
      analysis of historical data using the PACE Continuous Innovation IndicatorsTM
      (CII).
AB  - Background: There is an active debate about the role that endpoints other than
      overall survival (OS) should play in the drug approval process. Yet the term
      'surrogate endpoint' implies that OS is the only critical metric for regulatory
      approval of cancer treatments. We systematically analyzed the relationship
      between U.S. Food and Drug Administration (FDA) approval and publication of OS
      evidence to understand better the risks and benefits of delaying approval until
      OS evidence is available. Scope: Using the PACE Continuous Innovation Indicators
      (CII) platform, we analyzed the effects of cancer type, treatment goal, and year
      of approval on the lag time between FDA approval and publication of first
      significant OS finding for 53 treatments approved between 1952 and 2016 for 10
      cancer types (n = 71 approved indications). Findings: Greater than 59% of
      treatments were approved before significant OS data for the approved indication
      were published. Of the drugs in the sample, 31% had lags between approval and
      first published OS evidence of 4 years or longer. The average number of years
      between approval and first OS evidence varied by cancer type and did not reliably
      predict the eventual amount of OS evidence accumulated. Conclusions: Striking the
      right balance between early access and minimizing risk is a central challenge for
      regulators worldwide. We illustrate that endpoints other than OS have long helped
      to provide timely access to new medicines, including many current standards of
      care. We found that many critical drugs are approved many years before OS data
      are published, and that OS may not be the most appropriate endpoint in some
      treatment contexts. Our examination of approved treatments without significant OS
      data suggests contexts where OS may not be the most relevant endpoint and
      highlights the importance of using a wide variety of fit-for-purpose evidence
      types in the approval process.

PMID- 29167694
TI  - Computational modeling to improve treatments for essential tremor.
AB  - Essential tremor (ET) is a neurological disorder of unknown etiology that is
      typically characterized by an involuntary periodic movement of the upper limbs.
      No longer considered monosymptomatic, ET patients often have additional motor and
      even cognitive impairments. Although there are several pharmacological
      treatments, no drugs have been developed specifically for ET [1], and 30-70% of
      patients are medication-refractory [2]. A subset of medication-refractory
      patients may benefit from electrical deep brain stimulation (DBS) of the ventral
      intermediate nucleus of the thalamus (VIM), which receives cerebellar inputs.
      Abnormal cerebellar input to VIM is presumed to be a major contributor to tremor
      symptoms, which is alleviated by DBS. Computational modeling of the effects of
      DBS in VIM has been a powerful tool to design DBS protocols to reduce tremor
      activity. However, far less is known about how these therapies affect non-tremor
      symptoms, and more experimental and computational modeling work is required to
      address these growing considerations. Models capable of addressing multiple
      facets of ET will lead to novel, more efficient treatment.

PMID- 29167695
TI  - Total energy expenditure of 10- to 12-year-old Japanese children measured using
      the doubly labeled water method.
AB  - Background: To establish Japanese children's estimated energy requirements, total
      energy expenditure (TEE) data measured using the doubly labeled water (DLW)
      method is needed. This study aimed to 1) obtain basic TEE data from Japanese
      children measured using DLW (TEEDLW), 2) compare TEEDLW with TEE estimated by
      various estimation formulas to calculate their accuracy, and 3) develop a new
      equation to estimate TEE using body composition and pedometers. Methods: TEE was
      measured using DLW in 56 10- to 12-year-old Japanese children (33 boys, 23
      girls). Physical activity level (PAL) was calculated by dividing TEEDLW by
      estimated resting energy expenditure. To assess their physical activity,
      participants wore pedometers during the 7-d DLW period. Total body water was
      calculated from 2H and 18O; fat-free mass (FFM) and fat mass (FM) were then
      determined. Results: In boys and girls of normal weight, TEEDLW was 2067 +/- 230
      kcal/d and 1830 +/- 262 kcal/d, respectively. Average PAL was 1.58 +/- 0.17. FFM
      was strongly related to TEE (r = 0.702, p < 0.01). After adjusting for FFM and
      FM, step count was significantly associated with TEE (r = 0.707, p < 0.01). The
      TEE estimation formula used in the Dietary Reference Intakes (DRI) for the United
      States and Canada estimated TEEDLW with high accuracy (bias: 2.0%) in both sexes.
      We developed new equations for TEE consisting of FFM and step count, which
      accounted for 68% and 65% of TEE variance in boys and girls, respectively: boys,
      47.1 * FFM (kg) + 0.0568 * step count (steps/d) - 122, and girls, 55.5 * FFM (kg)
      + 0.0315 * step count (steps/d) - 117. Conclusions: The TEE in 10- to 12-year-old
      Japanese children measured using DLW was approximately 7% lower for boys and 12%
      lower for girls compared to the current Japanese DRI. If PAL can be accurately
      determined, the equation in the DRI for the United States and Canada may be
      applicable to Japanese children. In addition, TEE could be predicted using FFM
      and step count.

PMID- 29167696
TI  - Racial/ethnic differences in video game and Internet use among US adolescents
      with mental health and educational difficulties.
AB  - Video game and Internet use can be associated with poor mental health and
      educational outcomes among adolescents. Racial/ethnic minority youth use these
      media more than White youth. Video game and Internet use among adolescents with
      mental health and educational difficulties may therefore differ by race/ethnicity
      in clinically meaningful ways. We analyzed a representative sample of 8th grade
      students in the United States from the Early Childhood Longitudinal Survey
      Kindergarten (N=6,700). Stratifying by gender, we assessed racial/ethnic
      differences in the associations between video game and Internet use, mental
      health, and reading and math achievement. Significant minority-White differences
      were identified in associations between media use and mental health and
      educational achievement. Video game use was relatively high among black females
      with prior mental health diagnoses and Asian-American males with high
      internalizing symptoms. Understanding video game and Internet use among
      racial/ethnic minority youth with mental health and educational difficulties may
      improve clinical practice.

PMID- 29167697
TI  - Young lives disrupted: gender and well-being among adolescent Syrian refugees in
      Lebanon.
AB  - Background: The conflict in Syria that began in 2011 has resulted in the exodus
      of over 5 million Syrian refugees to neighbouring countries, with more than one
      million refugees currently registered by UNHCR in Lebanon. While some are living
      in tented settlements, the majority are living in strained conditions in rented
      accommodation or collective shelters in the Bekaa Valley next to Syria.
      Adolescents are particularly vulnerable in any crisis. In 2013-4, the American
      University in Beirut in collaboration with the Women's Refugee Commission, Johns
      Hopkins and Save the Children, sought to understand the specific experiences of
      very young adolescents, those 10-14 years of age, in this protracted crisis
      context. Methods: The study was conducted in 2014 in Barelias and Qabelias - two
      urban areas located close to each other in the Beka'a valley that has a large
      concentration of Syrian refugees. Focus group discussions (FGDs), including
      community mapping and photo elicitation, were conducted with 10-12 and 13-14 year
      old Syrian refugee adolescents, in order to obtain information about their
      experiences and perspectives. FGDs were also implemented with 15-16 year old
      Syrian refugees and separately also with adult refugees, to consider their
      perspectives on the needs and risks of these adolescents. Results: A total of 16
      FGD (8 for each sex, with 6-9 participants in each) were conducted in Arabic
      across the two sites, with 59 female participants and 59 male participants. The
      experiences and risks faced by these adolescents were significantly impacted by
      economic strain and loss of educational opportunities during displacement, and
      only a minority of adolescents in the study reported attending school.
      Additionally, on-going protection risks for girls were felt to be higher due to
      the crisis and displacement. In Lebanon this has resulted in increased risks of
      child marriage and limitations in mobility for adolescent girls. Adolescents,
      themselves expressed tensions with their Lebanese counterparts and feared verbal
      attacks and beatings from school-aged Lebanese male youth. Conclusions: Families
      and adolescents have been dramatically affected by the conflict in Syria, and the
      resulting forced displacement. The loss of educational opportunities is perhaps
      the most significant effect, with long-term devastating outcomes. Additionally,
      the futures of Syrian girls are deeply affected by new protection concerns,
      particularly as they are exposed to an unfamiliar and more liberal society in
      Lebanon. Child marriage and limitations in their mobility - particularly for
      girls - are presented by families as coping strategies to these risks.
      Programming is needed to ensure sustained education access for all adolescents,
      and to educate very young adolescents and their parents on managing their own
      health and well-being, given the multiple strains. More effort is needed to
      encourage positive interaction between adolescent Lebanese and adolescent Syrian
      refugees.

PMID- 29167699
TI  - A qualitative study exploring child marriage practices among Syrian conflict
      affected populations in Lebanon.
AB  - Background: Recent reports have suggested that child marriage among Syrians may
      be increasing as a result of displacement and conflict. This study sought to
      gather qualitative data about the factors that promote child marriage practices
      among Syrian refugees in Al Marj area in the Bekaa valley, Lebanon, where the
      majority of Syrian refugees have settled in Lebanon. The second aim of this study
      was to generate recommendations on how to mitigate the drivers and consequences
      of child marriage practices based on the findings. Methods: Eight focus group
      discussions were conducted separately with married and unmarried young women and
      mothers and fathers of married and unmarried women. Furthermore, researchers
      conducted 11 key informant interviews with service providers and stakeholders to
      understand how conflict and displacement influenced marriage practices of Syrian
      refugees in Al Marj community. Results: Although child marriage was a common
      practice in pre-conflict Syria, new factors seem to contribute to a higher risk
      of child marriage among Syrian refugees in Lebanon. Respondents cited conflict-
      and displacement-related safety issues and feeling of insecurity, the worsening
      of economic conditions, and disrupted education for adolescent women as driving
      factors. Service providers, young women, and parents also reported changes in
      some marriage practices, including a shorter engagement period, lower bride
      price, change in cousin marriage practices, and a reduced age at marriage.
      Conclusions: Recommendations for interventions to mitigate the drivers of child
      marriage and its negative consequences should be built on a clear understanding
      of the local refugee context and the drivers of child marriage in refugee
      settings. Interventions should involve multiple stakeholders, they should be
      adjusted to target each specific context, age group and marital status. For these
      interventions to be effective, they should be addressed concurrently, and they
      should be delivered in a culturally sensitive and practical manner.

PMID- 29167698
TI  - Transitions into puberty and access to sexual and reproductive health information
      in two humanitarian settings: a cross-sectional survey of very young adolescents
      from Somalia and Myanmar.
AB  - Background: Very young adolescents (VYA) in humanitarian settings are largely
      neglected in terms of sexual and reproductive health (SRH). This study describes
      the characteristics of VYA aged 10-14 years in two humanitarian settings,
      focusing on transitions into puberty and access to SRH information. Methods: Data
      were collected through a cross-sectional survey with Somali VYA residing in the
      Kobe refugee camp in Ethiopia (N = 406) and VYA from Myanmar residing in the Mae
      Sot and Phop Phra migrant communities in Thailand (N = 399). The average age was
      12 years (about half were girls) in both communities. Participants were recruited
      using multi-stage cluster-based sampling with probability proportional to size in
      each site. Descriptive statistics were used to describe the sociodemographic,
      family, peer, and schooling characteristics and to explore transitions into
      puberty and access to SRH information. Results: Most VYA in both sites reported
      living with both parents; nine in ten reported feeling that their
      parents/guardians care about them, and over half said that their
      parents/guardians monitor how and with whom they spend their free time. High
      proportions in both sites were currently enrolled in school (91.4% Somali, 87.0%
      from Myanmar). Few VYA, particularly those aged 10-12, reported starting puberty,
      although one in four Somali indicated not knowing whether they did so. Most girls
      from Myanmar who had started menstruating reported access to menstrual hygiene
      supplies (water, sanitation, cloths/pads). No Somali girls reported access to all
      these supplies. While over half of respondents in both sites reported learning
      about body changes, less than 20% had learnt about pregnancy and the majority
      (87.4% Somali, 78.6% from Myanmar) indicated a need for more information about
      body changes. Parents/guardians were the most common source of SRH information in
      both sites, however VYA indicated that they would like more information from
      friends, siblings, teachers and health workers. Conclusions: This study
      highlights gaps in SRH information necessary for healthy transitions through
      puberty and supplies for menstrual hygiene in two humanitarian settings. VYA in
      these settings expressed closeness to their parents/guardians and the majority
      were in school. Introducing early SRH interventions that involve parents and
      educational centers may thus yield promising results, providing VYA with the
      necessary skills for understanding and dealing with their pubertal and sexual
      development.

PMID- 29167700
TI  - Situational analysis to inform development of primary care and community-based
      mental health services for severe mental disorders in Nepal.
AB  - Background: Nepal is representative of Low and Middle Income Countries (LMIC)
      with limited availability of mental health services in rural areas, in which the
      majority of the population resides. Methods: This formative qualitative study
      explores resources, challenges, and potential barriers to the development and
      implementation of evidence-based Comprehensive Community-based Mental Health
      Services (CCMHS) in accordance with the mental health Gap Action Programme
      (mhGAP) for persons with severe mental health disorders and epilepsy. Focus Group
      Discussions (FGDs, n = 9) and Key-Informant Interviews (KIIs, n = 26) were
      conducted in a rural district in western Nepal. Qualitative data were coded using
      the Framework Analysis Method employing QSR NVIVO software. Results: Health
      workers, general community members, and persons living with mental illness
      typically attributed mental illness to witchcraft, curses, and punishment for
      sinful acts. Persons with mental illness are often physically bound or locked in
      structures near their homes. Mental health services in medical settings are not
      available. Traditional healers are often the first treatment of choice. Primary
      care workers are limited both by lack of knowledge about mental illness and the
      inability to prescribe psychotropic medication. Health workers supported
      upgrading their existing knowledge and skills through mhGAP resources. Health
      workers lacked familiarity with basic computing and mobile technology, but they
      supported the introduction of mobile technology for delivering effective mental
      health services. Persons with mental illness and their family members supported
      the development of patient support groups for collective organization and
      advocacy. Stakeholders also supported development of focal community resource
      persons to aid in mental health service delivery and education. Conclusion:
      Health workers, persons living with mental illness and their families, and other
      stakeholders identified current gaps and barriers related to mental health
      services. However, respondents were generally supportive in developing community
      based care in rural Nepal.

PMID- 29167701
TI  - Xylose induces cellulase production in Thermoascus aurantiacus.
AB  - Background: Lignocellulosic biomass is an important resource for renewable
      production of biofuels and bioproducts. Enzymes that deconstruct this biomass are
      critical for the viability of biomass-based biofuel production processes. Current
      commercial enzyme mixtures have limited thermotolerance. Thermophilic fungi may
      provide enzyme mixtures with greater thermal stability leading to more robust
      processes. Understanding the induction of biomass-deconstructing enzymes in
      thermophilic fungi will provide the foundation for strategies to construct hyper
      production strains. Results: Induction of cellulases using xylan was demonstrated
      during cultivation of the thermophilic fungus Thermoascus aurantiacus. Simulated
      fed-batch conditions with xylose induced comparable levels of cellulases. These
      fed-batch conditions were adapted to produce enzymes in 2 and 19 L bioreactors
      using xylose and xylose-rich hydrolysate from dilute acid pretreatment of corn
      stover. Enzymes from T. aurantiacus that were produced in the xylose-fed
      bioreactor demonstrated comparable performance in the saccharification of
      deacetylated, dilute acid-pretreated corn stover when compared to a commercial
      enzyme mixture at 50  degrees C. The T. aurantiacus enzymes retained this
      activity at of 60  degrees C while the commercial enzyme mixture was largely
      inactivated. Conclusions: Xylose induces both cellulase and xylanase production
      in T. aurantiacus and was used to produce enzymes at up to the 19 L bioreactor
      scale. The demonstration of induction by xylose-rich hydrolysate and
      saccharification of deacetylated, dilute acid-pretreated corn stover suggests a
      scenario to couple biomass pretreatment with onsite enzyme production in a
      biorefinery. This work further demonstrates the potential for T. aurantiacus as a
      thermophilic platform for cellulase development.

PMID- 29167703
TI  - Spin-wave propagation in cubic anisotropy materials.
AB  - The information carrier of modern technologies is the electron charge whose
      transport inevitably generates Joule heating. Spin-waves, the collective
      precessional motion of electron spins, do not involve moving charges and thus
      avoid Joule heating [1-3]. In this respect, magnonic devices in which the
      information is carried by spin-waves attract interest for low-power computing.
      However implementation of magnonic devices for practical use suffers from low
      spin-wave signal and on/off ratio. Here we demonstrate that cubic anisotropy
      materials can enhance spin-wave signals by improving spin-wave amplitude as well
      as group velocity and attenuation length. Furthermore, cubic anisotropy material
      shows an enhanced on/off ratio through a laterally localized edge mode, which
      closely mimics the gate-controlled conducting channel in traditional field-effect
      transistors. These attractive features of cubic anisotropy materials will
      invigorate magnonics research towards wave-based functional devices.

PMID- 29167702
TI  - Production of the versatile cellulase for cellulose bioconversion and cellulase
      inducer synthesis by genetic improvement of Trichoderma reesei.
AB  - Background: The enzymes for efficient hydrolysis of lignocellulosic biomass are a
      major factor in the development of an economically feasible cellulose
      bioconversion process. Up to now, low hydrolysis efficiency and high production
      cost of cellulases remain the significant hurdles in this process. The aim of the
      present study was to develop a versatile cellulase system with the enhanced
      hydrolytic efficiency and the ability to synthesize powerful inducers by
      genetically engineering Trichoderma reesei. Results: In our study, we employed a
      systematic genetic strategy to construct the carbon catabolite-derepressed strain
      T. reesei SCB18 to produce the cellulase complex that exhibited a strong
      cellulolytic capacity for biomass saccharification and an extraordinary high beta
      glucosidase (BGL) activity for cellulase-inducing disaccharides synthesis. We
      first identified the hypercellulolytic and uracil auxotrophic strain T. reesei
      SP4 as carbon catabolite repressed, and then deleted the carbon catabolite
      repressor gene cre1 in the genome. We found that the deletion of cre1 with the
      selectable marker pyrG led to a 72.6% increase in total cellulase activity, but a
      slight reduction in saccharification efficiency. To facilitate the following
      genetic modification, the marker pyrG was successfully removed by homologous
      recombination based on resistance to 5-FOA. Furthermore, the Aspergillus niger
      BGLA-encoding gene bglA was overexpressed, and the generated strain T. reesei
      SCB18 exhibited a 29.8% increase in total cellulase activity and a 51.3-fold
      enhancement in BGL activity (up to 103.9 IU/mL). We observed that the cellulase
      system of SCB18 showed significantly higher saccharification efficiency toward
      differently pretreated corncob residues than the control strains SDC11 and SP4.
      Moreover, the crude enzyme preparation from SCB18 with high BGL activity
      possessed strong transglycosylation ability to synthesize beta-disaccharides from
      glucose. The transglycosylation product was finally utilized as the inducer for
      cellulase production, which provided a 63.0% increase in total cellulase activity
      compared to the frequently used soluble inducer, lactose. Conclusions: In
      summary, we constructed a versatile cellulase system in T. reesei for efficient
      biomass saccharification and powerful cellulase inducer synthesis by
      combinational genetic manipulation of three distinct types of genes to achieve
      the customized cellulase production, thus providing a viable strategy for further
      strain improvement to reduce the cost of biomass-based biofuel production.

PMID- 29167704
TI  - Metagenomic analysis of intertidal hypersaline microbial mats from Elkhorn
      Slough, California, grown with and without molybdate.
AB  - Cyanobacterial mats are laminated microbial ecosystems which occur in highly
      diverse environments and which may provide a possible model for early life on
      Earth. Their ability to produce hydrogen also makes them of interest from a
      biotechnological and bioenergy perspective. Samples of an intertidal microbial
      mat from the Elkhorn Slough estuary in Monterey Bay, California, were
      transplanted to a greenhouse at NASA Ames Research Center to study a 24-h diel
      cycle, in the presence or absence of molybdate (which inhibits biohydrogen
      consumption by sulfate reducers). Here, we present metagenomic analyses of four
      samples that will be used as references for future metatranscriptomic analyses of
      this diel time series.

PMID- 29167705
TI  - Comparative analysis of impacted upper canines: Panoramic radiograph Vs Cone Beam
      Computed Tomography.
AB  - Background: The use of CBCT exam in the study of IMC is not new. However, it's
      still not known in what specific aspects CBCT exam shows a better result than
      then conventional exams. The aim of this study was to compare and conclude in
      what way the opinion regarding upper canine impaction differed when observing a
      panoramic image compared to the observation of a set of CBCT reconstructions.
      Material and Methods: Twenty patients (10 males and 10 females) with a total of
      28 impacted maxillary canines were identified from the database of the Department
      of Dentistry, Faculty of Medicine, University of Coimbra. For each canine, two
      different images were available: a panoramic image and a set of CBCT
      reconstructions. After a random distribution of both groups images, nine
      orthodontists completed a questionnaire where they were asked to evaluate ten
      different questions regarding canine impaction. Statistic analysis was performed
      using Cronbach's alpha statistics, Kappa statistics and McNemar test, considering
      p<0,05 statistically significant. Results: This study showed differences between
      the two images regarding tooth position. A statistical significant poor agreement
      was found between the two methods for the mesio-distal position of the apex
      (k=0,388, p<0,001) and for the labio-palatal tip cusp position (k=0,035,
      p=0,114). The adjacent root resorption showed a poor and very poor agreement
      between the two methods. Every other items were scored with an agreement between
      modalities ranging from moderate to strong. Conclusions: The analyses of
      panoramic images versus CBCT images reconstructions provided different
      information regarding tooth position (especially concerning the mesio-distal apex
      position and the labio-palatal cusp position) but also in the assessment of root
      resorption. Further investigation should be done to determine in what cases CBCT
      exam has a clear advantage over conventional 2D exams, justifying its use. Key
      words:Cone-Beam Computed Tomography, Orthodontics, Impacted Tooth, Root
      resorption.

PMID- 29167706
TI  - The effect of oxalate-based desensitizers on the microleakage and shear bond
      strength of resin modified glass ionomer.
AB  - Background: The first line of intervention to alleviate tooth sensitivity is to
      use dentin desensitizers such as oxalate-based desensitizers. When the dentin
      sensitivity continues even after application of desensitizers the next
      intervention would be restoration of the lesion. The aim of this in vitro study
      was to investigate the effect of prior application of oxalate-based desensitizer
      on the marginal microleakage and shear bond strength of resin modified glass
      ionomer (RMGI) restorations. Material and Methods: In order to prepare the
      specimens for microleakage test standard class v cavities were prepared on buccal
      surfaces of 45 teeth. The specimens were randomly divided into three equal
      groups. In control group, the cavities were restored with RMGI. In group 2,
      oxalate-based desensitizer was applied and the specimens were kept in distilled
      water for 14 days before restoration. In group 3 the specimens were prepared
      similar to group 2 and the surface of the cavities were slightly cut with bur
      before restoration. Methyleneblue penetration was evaluated using
      stereomicroscope. The data were analyzed using non-parametric tests. For shear
      bond strength test cervical dentin specimens were prepared and were divided into
      3 groups. Surface treatments were similar to microleakage test. RMGI was packed
      into cylindrical plastic molds which were placed on the cut surface of the tooth
      and light cured. The data were analyzed by one-way ANOVA. Results: There was not
      any significant difference in dye penetration in dentin margins among the groups,
      but microleakage in enamel margins of group 2 and 3 was higher than group 1.
      There was no significant difference in shear bond strength among the groups (p
      =0.285). Conclusions: Non carious cervical lesions which were treated for
      hypersensitivity with oxalate-based desensitizers could be restored with resin
      modified glass ionomer if the hypersensitivity persists. Key words:Dentin
      hypersensitivity, oxalate-based desensitizers, microleakage, shear bond strength.

PMID- 29167707
TI  - Solubility and pH of bioceramic root canal sealers: A comparative study.
AB  - Background: This study compared the solubility and the pH of different root canal
      sealers in vitro. Material and Methods: BioRootTMRCS, TotalFill BC Sealer, MTA
      Fillapex, SealapexTM, AH Plus, EasySeal, Pulp Canal SealerTM and N2 were tested.
      Similar specimens were prepared using ring molds with an internal diameter of 20
      +/- 0,1 mm and a height of 1,5 +/- 0,1 mm and digitally weighted to register the
      mass of each specimen before and after immersion in distilled water. Solubility
      was determined after 24 hours and statistically analysed using a one-way ANOVA
      test and post-hoc Tukey test. The pH value was measured by a digital pH meter
      after 3 and 24 hours from manipulation. Results: BioRootTMRCS and TotalFill BC
      Sealer showed significantly higher solubility (P<0.05). All the remnant root
      canal sealers fulfilled the requirements of solubility of the International
      Standard Organization 6876 demonstrating a weight loss of less than 3%.
      BioRootTMRCS and Totalfill BC Sealer exhibited high alkaline pH over time
      (P<0.05); the alkalinity of the other tested cements was significantly lower.
      Conclusions: The prolonged alkalinity of bioceramic sealer matched the increase
      in solubility. This may encourage their biological and antimicrobial effects, but
      the ongoing solubility may impact their ability to prevent apical leakage. Key
      words:pH, root canal sealers, solubility.

PMID- 29167708
TI  - Tooth Abnormalities In Individuals With Unilateral Alveolar Clefts: A Comparison
      Between Sides Using Cone-Beam Computed Tomography.
AB  - Background: Tooth abnormalities are most often present in individuals with oral
      clefts than general population, and lead to a long-term impact on facial anatomy
      and self-esteem. The purpose of this study was to compare the proportion of
      dental anomalies between the cleft side and non-cleft side in individuals with
      non-syndromic unilateral alveolar clefts (AC). Material and Methods: Twenty cone
      beam computed tomography (CBCT) scans were converted into three-dimensional (3D)
      virtual models. The dental anomalies considered were: tooth agenesis;
      supernumerary teeth; giroversion; and microdontia. Statistical analysis was
      performed using the McNemar's test and Fisher's exact test (p<0.05). Results:
      Statistically significant differences were not found either between the
      prevalence of individuals with dental abnormalities on the non-cleft side and the
      sides of the AC (p = 1.00), or sex (p = 0.36). Tooth agenesis was the most
      prevalent dental anomaly (55.6%). On the cleft side the lateral incisor was tooth
      most involved by dental anomalies; and the second premolar was the most affected
      on the non-cleft side. Conclusions: This study showed a high frequency of dental
      anomalies in the cleft individuals and indicated that the side of AC and sex do
      not interfere in the proportion of dental anomalies on non-cleft side. Key
      words:Cone beam computed tomography, Hypodontia, Tooth abnormalities.

PMID- 29167709
TI  - Trends over Time in Dental Caries status in Urban and Rural Thai Children.
AB  - Background: Historically, the prevalence of dental caries was higher in urban
      areas than rural areas of Thailand. This study aim to examine the time trends in
      caries status in children in Thailand. Material and Methods: Linear regression
      was used to examine trend of dental caries prevalence and mean number of teeth
      with caries, filled and missing due to caries (dmft/DMFT) in urban and rural, of
      3-, 5-6 and 12-year olds from seven Thailand National Oral Health Surveys
      conducted approximately every 5 years from 1977 to 2012. Results: There were
      declines in the caries prevalence and mean dmft/DMFT in every age group.
      Significant results were observed in the mean dmft of 3 year-olds and the mean
      DMFT of 12 year-olds (p= 0.03 and p=0.05, respectively). A significant trend of
      declining prevalence of dental caries was observed in urban children ages 5-6
      (p=0.002), along with urban 12 year-olds (p<0.001). A declining trend of mean
      dmft for 3 and 5-6 year-olds, and mean DMFT for 12 year-olds was observed in both
      rural and urban areas, but significant results were shown in urban 3 and 5-6 year
      olds (P=0.04, and p<0.001, respectively), and urban 12 year-olds (p=0.001). For
      restoration outcome, both urban and rural of all age groups have an increasing
      trend of mean ft/FT index. Conclusions: There have been differences over time in
      the prevalence and quantity of dental caries between urban and rural school
      children. A significant reduction was observed in urban areas. More effort needs
      to be given to supply rural areas in order to have fair and equal access of all
      citizens to oral health care. Key words:Dental caries, prevalence, children,
      Thailand, rural, urban, time trend, national survey.

PMID- 29167710
TI  - Influence of nicotine on machined- and anodized-surface implants. Histometric
      analysis.
AB  - Background: The nicotine may generate a influence on bone repair and longevity of
      dental implants. This fact makes studies to improve the surface of the implants
      are constantly conducted. This study aimed to evaluate the influence of
      subcutaneous nicotine injection in the osseointegration process on different
      implant surfaces, through histomorphometric analysis. Material and Methods:
      Therefore, twenty-two male rabbits were randomly distributed into two groups
      according to the subcutaneous injections: (1) nicotine, 3 mg/day/kg and (2) 0.9%
      NaCI, 3 mL/day/kg, three times a day. Subgroups were then designated - machined
      and anodized dental implants were installed in the right and left tibia bones,
      respectively. The animals were subjected to euthanasia after periods of eight
      weeks for histomorphometric analysis. The bone samples with implants were removed
      and the routine histological processing was performed. Next, the images obtained
      from the blades were evaluated by the Image ToolTM software, assessing the
      osseointegrated areas of implants (BIC), in pixels. Data obtained were subjected
      to intergroup statistical analysis through the Kruskal-Wallis non-parametric test
      (alpha=5%). Results: The test result showed no statistically significant
      difference among the groups studied (p=0.446). Conclusions: Based on the
      methodology studied, it is concluded that the daily application of low doses of
      nicotine did not interfere with the osseointegration of machined and anodized
      implants. Key words:Bone-implant interface, implants, osseointegration.

PMID- 29167711
TI  - The effect of pre-cure bracket movement on shear bond strength during placement
      of orthodontic brackets, an in vitro study.
AB  - Background: The purpose of this study was to determine the influence of linear
      and rotational pre-cure bracket displacement during the bonding procedure on
      shear bond strength (SBS) of orthodontic brackets. Material and Methods:
      Stainless steel orthodontic premolar brackets were bonded to the buccal surfaces
      of 50 human pre-molars with a conventional two-step bonding protocol. Extracted
      human pre-molars were divided into 5 groups (n=10/group). In the Control Group,
      the brackets were bonded with no pre-cure bracket displacement or rotation. The
      Rotation Group was bonded with 45 degrees of pre-cure rotation. The Displacement
      Group was bonded with 2mm pre-cure linear displacement. The Rotation-Displacement
      Group was bonded with pre-cure movements of 45o counter-clockwise rotation and
      2mm displacement. The Slippage Group was bonded with 2mm each of mesial and
      distal pre-cure linear displacement. Photo-activation was carried out on the
      lateral sides of the bracket. Shear debonding force was measured, 24 hours after
      initial bonding, with an Instron universal testing machine using a knife-edged
      chisel. Data was analyzed using one-way ANOVA test. Adhesive Remnant Index (ARI)
      was scored under 15x magnification. The ARI data was analyzed using the Chi
      square test (p -value < 0.05). Results: No statistically significant differences
      were detected among the control and experimental groups (p = 0.331). The rotation
      and displacement group showed the highest mean SBS than all other groups. Mean
      SBS for all groups were above the clinically acceptable range. No statistically
      significant differences were detected in ARI scores among groups (p = 0.071).
      Conclusions: Linear and rotational pre-cure bracket displacements do not appear
      to effect the shear bond strength of orthodontic brackets. Key words:Shear bond
      strength, orthodontic bracket, displacement, rotation, adhesive remnant index,
      pre-cure movement.

PMID- 29167712
TI  - Vertical Root Fracture initiation in curved roots after root canal preparation: A
      dentinal micro-crack analysis with LED transillumination.
AB  - Background: One of the causative factors of root defects is the increased
      friction produced by rotary instrumentation. A high canal curvature may increase
      stress, making the tooth more susceptible to dentinal cracks. The purpose of this
      study was to evaluate dentinal micro-crack formation with the ProTaper NEXT and
      ProTaper Universal systems using LED transillumination, and to analyze the micro
      crack generated at the point of maximum canal curvature. Material and Methods: 60
      human mandibular premolars with curvatures between 30-49 degrees  and radii
      between 2-4 mm were used. The root canals were instrumented using the Protaper
      Universal(r) and Protaper NEXT(r) systems, with the aid of the Proglider(r)
      system. The obtained samples were sectioned transversely before subsequent
      analysis with LED transillumination at 2 mm and 8 mm from the apex and at the
      point of maximum canal curvature. Defects were scored: 0 for no defects; and 1
      for micro-cracks. Results: Root defects were not observed in the control group.
      The ProTaper NEXT system caused fewer defects (16.7%) than the ProTaper Universal
      system (40%) (P<0.05). The ProTaper Universal system caused significantly more
      micro-cracks at the point of maximum canal curvature than the ProTaper NEXT
      system (P<0.05). Conclusions: Rotary instrumentation systems often generate root
      defects, but the ProTaper NEXT system generated fewer dentinal defects than the
      ProTaper Universal system. A higher prevalence of defects was found at the point
      of maximum curvature in the ProTaper Universal group. Key words:Curved root,
      Micro-crack, point of maximum canal curvature, ProTaper NEXT, ProTaper Universal,
      Vertical root fracture.

PMID- 29167713
TI  - The effect of social geographic factors on the untreated tooth decay among head
      start children.
AB  - Background: Disparities among untreated dental caries exist for children from low
      income families in the United States. Understanding of the mechanism of the
      disparities is required to reduce it and social geographic factors are one of the
      important influences. Although the effect of fluoridated water has been well
      reported, studies of other sociogeograpic factors, such as the density of
      available dentists, are still very limited. The objective of this study is to
      explore the effect of sociogeographic factors on the number of primary teeth with
      untreated dental caries among children from low-income families who are enrolled
      in Head Start programs throughout Northeast Ohio of the United States. Material
      and Methods: This was a cross-sectional chart review study. Three hundred-eighty
      eight charts were reviewed, and the number of primary teeth with untreated dental
      caries (dt) and the children's addresses were retrieved. The sociogeographic
      variables, including fluoridated water availability and the density of available
      dentists who accept a government-supported insurance (Medicaid dentists), were
      collected. Results: The mean (standard deviation) of children's age was 3.51
      (1.14) years with a range of 7 months to 5 years. A negative binomial regression
      model analysis, which used dt as a dependent variable and children's
      characteristic factors (i.e. age, gender, insurance type, and total number of
      primary teeth) and sociogeographic factors (i.e. Population, total number of
      Medicaid dentists, density of Medicaid dentist, and Fluoride water availability)
      of cities, as independent variables, demonstrated that only the density of
      Medicaid dentist in the sociogeographic factors indicated a significant effect
      (Estimated beta-Coefficients (Standard Errors)=-0.003 (0.002), p=0.030).
      Conclusions: This study demonstrated a significant negative association between
      the density of available dentists and untreated dental caries among children from
      low-income families in Head Start programs in Northeast Ohio. Increasing
      available dentists may be a strategy to reduce the number of early childhood
      caries. Key words:Child, poverty, dental caries, Health Services Accessibility.

PMID- 29167714
TI  - Micro-CT study of the root canal anatomy of maxillary canines.
AB  - Background: This study aimed to describe the anatomy of maxillary canines from a
      Western Mexican sub-population using micro-computed tomography (micro-CT).
      Material and Methods: Maxillary canines (n=32) were scanned at 19.6um voxel
      resolution. Number and location of canals, the distance between the cemento
      enamel junction and apex, occurrence of accessory and lateral canals, presence of
      oval canals, number of foraminas as well as two- (area, perimeter, roundness,
      aspect ratio, major and minor diameters) and three-dimensional (volume, surface
      area, and SMI) analysis were performed. Data of two-dimensional analyses at 5
      different apical levels was statistically compared using Kruskal-Wallis tests
      (alpha=0.05). Results: Overall, 31 specimens had one root with a main canal
      (Vertucci type I). Mean distance from the apex to the cemento-enamel junction was
      16.32+/-2.27. Apical foraminas were present in 14 specimens (43.75%). No
      statistical differences were found in the two-dimensional analyses between the
      foramen and the 1 and 2mm apical levels (P >0.05). Conclusions: Maxillary canines
      presenting one root canal were present in a high percentage of cases (96%). The
      prevalence of long oval canals was <12% at the apical third and at least 37% of
      the sample showed more than one point of exit in the last apical 3mm. Key
      words:Maxillary canine, micro-computed tomography, root canal anatomy.

PMID- 29167715
TI  - Quality of the calcium-enriched mixture apical plug in simulated apexification
      model; Effect of different mixing and placement methods.
AB  - Background: Presence of voids at root canal wall-apical seal material interface
      gives rise to the entrapment of toxins and microorganisms, which might have a
      relationship with post treatment disease. The present study was carried out to
      evaluate the effect of different mixing (manual and ultrasonic) and placement
      (manual and manual in association with indirect ultrasonic) methods of Calcium
      enriched Mixture (CEM) cement on the number and dimensions of voids in the apical
      plug in simulated apexification models. Material and Methods: A total of 80 human
      maxillary central incisors with mature apices were selected. After simulation of
      the open apices, the teeth were divided into 4 groups (n=20) based on the mixing
      and placement techniques of CEM cement: group 1, manual mixing-manual placement;
      group 2, manual mixing-manual placement in association with indirect ultrasonic
      technique; group 3, ultrasonic mixing-manual placement; and group 4, ultrasonic
      mixing-manual placement in association with indirect ultrasonic technique. The
      samples were placed within gypsum sockets in which the periodontal ligament was
      reconstructed with polyether impression material. After placement the apical
      plugs, a wet piece of cotton was placed on canal orifices, followed by dressing
      with Cavit. The samples were incubated at 37 degrees C and 100% relative humidity
      for 7 days. Then the voids between the material and root canal walls were counted
      with the CBCT technique. The void dimensions were scored with the following
      scoring system: score 1, no voids; score 2, the void size less than half of the
      size of the evaluated cross-section; score 3, the void size larger than half of
      the size of the evaluated cross-section. Statistical analyses were carried out
      with chi-squared and Fisher's exact tests. Statistical significance was defined
      at P<0.05. Results: The maximum (7) and minimum (2) number of voids were detected
      in groups 1 and 2, respectively. The difference between these two groups was
      statistically significant (p<0.05). The differences in the number of voids
      between groups with similar mixing technique and different mixing techniques
      (i.e. groups 1 and 3 and groups 2 and 4) were not significant (p>0.05). Void
      dimensions in all the study groups were in score 2 category and no score 3 was
      recorded in the study groups. Conclusions: Under the limitations of the present
      study, manual placement in association with indirect ultrasonic technique was a
      proper technique to improve the quality of apical plug, considering the decrease
      in the number of voids. Key words:Apical plug, CEM cement, void.

PMID- 29167716
TI  - Oral manifestations of gastrointestinal disorders.
AB  - Background: A considerable number of gastrointestinal disorders (GIDs) of varied
      nature (inflammatory, infectious, genetic and other etiology) may produce
      alterations in the hard and soft oral tissues. Among these are Crohn's disease,
      ulcerative colitis, celiac and gastroesophageal reflux disease. Material and
      Methods: Article search was done using the National library of medicine (PubMed)
      database using different search terms and analyzed according to their importance.
      Results: A large variety of GIDs can give rise to oral lesions, including: RAS
      like ulceration, mucosal tags, cobblestoning, mucogingivitis, labial and facial
      swelling, pyostomatitis vegetans, disgeusia and dental abnormalities, among
      others. Although in most cases the gastrointestinal signs and symptoms highlight
      in the clinical picture, a considerable percentage of these patients are affected
      by oral manifestations before the onset of gastrointestinal symptoms. This
      lesions can cause significant functional and aesthetics damages as well
      deteriorate the patient quality of life. Conclusions: Although the frequency of
      oral manifestations is variable across GIDs and in most cases is non-specific,
      these alterations may precede the underlying disease and therefore can facilitate
      an opportune diagnosis. Key words:Gastrointestinal disorders, oral lesions, oral
      mucosal disorders.

PMID- 29167717
TI  - Composition and physicochemical properties of calcium silicate based sealers: A
      review article.
AB  - Background: Recently a new generation of endodontic sealers has been developed
      based on calcium silicate as MTA Fillapex, Endoseal MTA, Total Fill BC Sealer,
      EndoSequence BC Sealer, iRoot SP, Endo CPM sealer, MTA-Angelus and ProRoot Endo
      Sealer. A review of literature was conducted to discuss the composition,
      physicochemical properties, and clinical perspectives of calcium silicate based
      sealers. Material and Methods: A literature search was conducted in PubMed and
      web of knowledge databases with appropriate MeSh terms and keywords. A total of
      71 studies were reviewed for data extraction. Results and Conclusions: Calcium
      silicate based sealers showed suitable physical properties to be used as an
      endodontic sealer. However, its high solubility remains an important issue. They
      show good performance regarding calcium ion release, film thickness, and
      fowability. More researches are required about features of calcium silicate based
      sealers before recommending them for clinical applications. Key words:Calcium
      silicate, root canal filling materials, composition, physical properties.

PMID- 29167718
TI  - Preparation Prerequisites for Effective Irrigation of Apical Root Canal: A
      Critical Review.
AB  - Background: It is well recognized that disinfection of the complex root canal
      system at the apical root canal remains the most critical therapeutic measure to
      treat apical periodontitis. Material and Methods: Observational and experimental
      data in relation to the anatomy of the apical root canal in different tooth types
      and the cross sectional diameters of the apical part of the most commonly used
      hand and rotary files are critically reviewed. Results: The present data analysis
      confirm that the challenging issue of antibacterial efficacy of modern
      preparation protocols in non-surgical endodontics requires more attention to
      apical root canal irrigation as a balance between safety and effectiveness. Ex
      vivo investigations clearly indicate that a specific design of the chemo
      mechanical preparation is needed at the onset of RCT, more particularly in
      infected teeth. Design should be based on specific anatomical parameters, and
      must determine the appropriate size and taper of preparation as pre-requirements
      for effective and safe apical irrigation. Conclusions: The optimal irrigation
      protocols might be designed on the basis of technical specifications of the
      preparations procedures, such as the penetration depth, the type of the needle,
      the required time for continuous irrigant flow, the concentration of NaOCl, and
      the activation parameters. Key words:Endodontics, root canal treatment,
      instrumentation, irrigation, apical root canal.

PMID- 29167719
TI  - Is Khat (Catha edulis) chewing a risk factor for periodontal diseases? A
      systematic review.
AB  - Background: Khat (Catha edulis) chewing is a highly prevalent habit in the
      Arabian Peninsula and East Africa, and has recently spread to Western countries.
      The association between khat chewing and oral mucosal lesions is well documented
      in the literature. However, there is no concrete evidence on the association
      between khat chewing and periodontal disease. The purpose of this systematic
      review was to analyze the influence of khat chewing on periodontal health.
      Material and Methods: A literature search of PubMed, Scopus and Web of Sciences
      databases was carried out to identify relevant articles published from 1990 to
      May 2017. The inclusion criteria were all clinical studies that assessed the
      relationship between khat chewing and periodontal disease. Results: The search
      yielded 122 articles, of which 10 were included in this systematic review. Most
      of the studies exhibited a positive correlation between khat chewing and
      periodontal disease. Conclusions: Altogether, the analysis of the current
      evidence reveals that khat chewing is destructive to the periodontium and
      enhances the risk of periodontal disease progression. However, due to variability
      of studies, more longitudinal case-controlled studies are highly warranted to
      establish a causal relation between khat chewing and periodontal disease. Key
      words:Khat chewing, periodontal health, periodontal disease, risk factor.

PMID- 29167720
TI  - Peek polymer in orthodontics: A pilot study on children.
AB  - The purpose of the study has been making the orthodontic space maintainers in
      PEEK polymer (Polyetheretherketone) through a digital workflow. New digital
      technologies are taking hold in diagnosis, therapy and in dental laboratories.
      The digital world can help dentist in diagnosis and therapy: -diagnosis through
      the acquisition of radiographic images (CBCT) or scanners which allow the
      creation of 3D digital models - about therapy thanks to dental CAD CAM system. It
      consists of design devices through an dedicated software CAD and then realize
      devices through CAM system. We used digital system to improve the quality of the
      treatment and reduce costs. Peek polymer, subject of studies in recent years,
      thanking to its characteristics, resulted useful for this study. According to a
      nine month- follow up the devices were found comfortable, satisfying,
      personalized and minimally visible for the patients. These devices were found
      suitable to maintain the space. About material, thanks to its dimensional
      stability, mechanical strength but specially, thanks to its biocompatibility,
      PEEK was found as a very good material to build space maintainers. The workflow
      allowed a simulation of the treatment plan with a better collaboration and
      acceptance of the patient. Digital system reduced the systematic mistakes during
      the various phases and the production time. The digital system saved space
      creating a virtual plaster casts collection. Key words:PEEK, CAD/CAM system,
      space maintainers, orthodontic prevention.

PMID- 29167721
TI  - Clinical and radiographic features of pycnodysostosis: A case report.
AB  - Pycnodysostosis is a rare disorder that was first described in 1962; however, it
      was only in 1996 that the defective gene was discovered, which led to a better
      understanding of this disease. This study reports and discuss a case of
      pycnodysostosis. In addition, a search of articles published in PubMed-Medline
      was performed. The case was a 13-year-old girl who was referred to a private
      clinic for dental treatment. Clinical examination showed midface hypoplasia,
      prominent cheeks, a high nasal bridge, beaked nose, spoon-shaped fingers, frontal
      bossing, open fontanelles and dental alterations, findings compatible with
      pycnodysostosis. Patients with this disease also suffer from fractures because of
      bone hardness with almost no elasticity, a fact that requires special care
      particularly in the case of children and adolescents. The diagnosis of
      pycnodysostosis is made based on clinical and radiographic findings. Clinicians
      should be aware of this disorder to provide adequate dental treatment. Key
      words:Pycnodysostosis, developmental bone disease, imaging diagnosis.

PMID- 29167723
TI  - The Impact of Audio Book on the Elderly Mental Health.
AB  - Introduction: The growing elderly population calls mental health professionals to
      take measures concerning the treatment of the elderly mental disorders. Today in
      developed countries, bibliotherapy is used for the treatment of the most
      prevalent psychiatric disorders. Therefore, this study aimed to investigate the
      effects of audio book on the elderly mental health of Retirement Center of Shahid
      Beheshti University of Medical Sciences. Methods: This experimental study was
      conducted on 60 elderly people participated in 8 audio book presentation
      sessions, and their mental health aspects were evaluated through mental health
      questionnaire (SCL-90-R). Data were analyzed using SPSS 24. Results: Data
      analysis revealed that the mean difference of pretest and posttest of control
      group is less than 5.0, so no significant difference was observed in their mental
      health, but this difference was significant in the experimental group (more than
      5.0). Therefore, a significant improvement in mental health and its dimensions
      have observed in elderly people participated in audio book sessions. This
      therapeutic intervention was effective on mental health dimensions of paranoid
      ideation, psychosis, phobia, aggression, depression, interpersonal sensitivity,
      anxiety, obsessive-compulsive and somatic complaints. Conclusion: Considering the
      fact that our population is moving toward aging, the obtained results could be
      useful for policy makers and health and social planners to improve the health
      status of the elderly.

PMID- 29167722
TI  - Behavioral, Cognitive and Neural Markers of Asperger Syndrome.
AB  - Asperger syndrome (AS) is a subtype of Autism Spectrum Disorder (ASD)
      characterized by major problems in social and nonverbal communication, together
      with limited and repetitive forms of behavior and interests. The linguistic and
      cognitive development in AS is preserved which help us to differentiate it from
      other subtypes of ASD. However, significant effects of AS on cognitive abilities
      and brain functions still need to be researched. Although a clear cut pathology
      for Asperger has not been identified yet, recent studies have largely focused on
      brain imaging techniques to investigate AS. In this regard, we carried out a
      systematic review on behavioral, cognitive, and neural markers (specifically
      using MRI and fMRI) studies on AS. In this paper, behavior, motor skills and
      language capabilities of individuals with Asperger are compared to those in
      healthy controls. In addition, common findings across MRI and fMRI based studies
      associated with behavior and cognitive disabilities are highlighted.

PMID- 29167724
TI  - Analysis of Resting-State fMRI Topological Graph Theory Properties in
      Methamphetamine Drug Users Applying Box-Counting Fractal Dimension.
AB  - Introduction: Graph theoretical analysis of functional Magnetic Resonance Imaging
      (fMRI) data has provided new measures of mapping human brain in vivo. Of all
      methods to measure the functional connectivity between regions, Linear
      Correlation (LC) calculation of activity time series of the brain regions as a
      linear measure is considered the most ubiquitous one. The strength of the
      dependence obligatory for graph construction and analysis is consistently
      underestimated by LC, because not all the bivariate distributions, but only the
      marginals are Gaussian. In a number of studies, Mutual Information (MI) has been
      employed, as a similarity measure between each two time series of the brain
      regions, a pure nonlinear measure. Owing to the complex fractal organization of
      the brain indicating self-similarity, more information on the brain can be
      revealed by fMRI Fractal Dimension (FD) analysis. Methods: In the present paper,
      Box-Counting Fractal Dimension (BCFD) is introduced for graph theoretical
      analysis of fMRI data in 17 methamphetamine drug users and 18 normal controls.
      Then, BCFD performance was evaluated compared to those of LC and MI methods.
      Moreover, the global topological graph properties of the brain networks inclusive
      of global efficiency, clustering coefficient and characteristic path length in
      addict subjects were investigated too. Results: Compared to normal subjects by
      using statistical tests (P<0.05), topological graph properties were postulated to
      be disrupted significantly during the resting-state fMRI. Conclusion: Based on
      the results, analyzing the graph topological properties (representing the brain
      networks) based on BCFD is a more reliable method than LC and MI.

PMID- 29167725
TI  - Transdifferentiation of Human Dental Pulp Stem Cells Into Oligoprogenitor Cells.
AB  - Introduction: The nerve fibers in central nervous system are surrounded by myelin
      sheet which is formed by oligodendrocytes. Cell therapy based on oligodendrocytes
      and their precursors transplantation can hold a promising alternative treatment
      for myelin sheet repair in demyelinating diseases. Methods: Human Dental Pulp
      Stem Cells (hDPSCs) are noninvasive, autologous and easy available source with
      multipotency characteristics, so they are in focus of interest in regenerative
      medicine. In the present study, hDPSCs were differentiated into oligoprogenitor
      using glial induction media, containing Retinoic Acid (RA), basic Fibroblast
      Growth Factor (bFGF), Platelet-Derived Growth Factor (PDGF), N2 and B27. The
      differentiated Oligoprogenitor Cells (OPCs) were evaluated for nestin, Olig2, NG2
      and O4 using immunocytochemistry. Also, the expression of nestin, Olig2 and PDGFR
      alpha gens (neuroprogenitor and oligoprogenitor markers) were investigated via RT
      PCR technique. Results: The results indicate that glial differentiation medium
      induces the generation of oligoprogenitor cells as revealed via exhibition of
      specific glial markers, including Olig2, NG2 and O4. The expersion of nestin gene
      (neuroprogenitor marker) and Olig2 and PDGFR-alpha genes (oligoprogentor markers)
      were detected in treated hDPSCs at the end of the induction stage. Conclusion:
      hDPSCs can be induced to transdifferentiate into oligoprogenitor cells and
      respond to the routinely applied regents for glial differentiation of mesanchymal
      stem cells. These data suggest the hDPSCs as a valuable source for cell therapy
      in neurodegenerative diseases.

PMID- 29167726
TI  - Effects of Hydroalcoholic Extract of Soy on Learning, Memory and Synaptic
      Plasticity Deficits Induced by Seizure in Ovariectomized Rats.
AB  - Introduction: Previous studies have shown that seizure can induce cognitive
      impairment. On the other hand, soy phytoestrogens, which are mainly found in
      soybean (Glycine max (L.) Merr.), have beneficial effects on the nervous system.
      However, little is known about their probable effects on seizure. The present
      study aimed to examine the probable effects of soy extract, containing the
      phytoestrogen genistein on seizure-induced cognitive and synaptic plasticity
      impairment in Ovariectomized (OVX) rats. Methods: Rats were ovariectomized,
      implanted with guide cannula and then divided into 5 groups (n=7-8 in each
      group): PBS, KA, Saline-KA, Higher Dose Soy (HDS-KA), and Lower Dose Soy (LDS-KA)
      groups. Animals of the HDS-KA and LDS-KA groups received intraperitoneal
      administration of soy extract (20 and 2 mg/kg, respectively) and the Saline-KA
      group received normal saline once a day for 4 days. Sixty minutes after the last
      injection, Kainic Acid (KA) or PBS was injected into the left lateral ventricle
      via pre-implanted guide cannula to induce generalized seizures. The Morris water
      maze task and in vivo field potential recordings were conducted 7 days later.
      Results: Soy extract at both doses significantly improved learning impairment and
      at the higher dose (20 mg/kg) significantly prevented seizure-induced spatial
      memory impairment and deficit of long-term potentiation in the hippocampus.
      Conclusion: The soy extract containing the phytoestrogen genistein may have
      beneficial effects on memory deficit induced by seizure in OVX rats and this
      effect is accompanied by a beneficial effect on synaptic plasticity.

PMID- 29167727
TI  - The Effect of Repetitive Transcranial Magnetic Stimulation on Postural Stability
      After Acute Stroke: A Clinical Trial.
AB  - Introduction: Balance impairment is a common problem and a major cause of motor
      disability after stroke. Therefore, this study aimed to investigate whether low
      frequency repetitive Transcranial Magnetic Stimulation (rTMS) improves the
      postural balance problems in stroke patients. Methods: This randomized double
      blind clinical trial with 12 weeks follow-up was conducted on stroke patients.
      Treatment was carried with 1 Hz rTMS in contralateral brain hemisphere over the
      primary motor area for 20 minutes (1200 pulses) for 5 consecutive days. Static
      postural stability, Medical Research Council (MRC), Berg Balance Scale (BBS), and
      Fugl-Meyer assessments were evaluated immediately, 3 weeks and 12 weeks after
      intervention. Results: A total of 26 patients were enrolled (age range=53 to 79
      years; 61.5% were male) in this study. Administering rTMS produced a significant
      recovery based on BBS (df=86, 7; F=7.4; P=0.01), Fugl-Meyer Scale (df=86, 7;
      F=8.7; P<0.001), MRC score (df=87, 7; F=2.9; P=0.01), and static postural
      stability (df=87, 7; F=9.8; P<0.001) during the 12 weeks follow-up. Conclusion:
      According to the findings, rTMS as an adjuvant therapy may improve the static
      postural stability, falling risk, coordination, motor recovery, and muscle
      strength in patients with stroke.

PMID- 29167728
TI  - Predicting the Risk of Hearing Impairment Following the Cervical Spine Diseases
      by Measuring the Cervical Range of Movements: A Pilot Study.
AB  - Introduction: Cervical spine abnormalities can affect the ear vessels and or
      nerves with different mechanisms. Ear dysfunctions following cervical spine
      injuries can be manifested as hearing loss, vertigo, or tinnitus. Usually,
      cervical spine injuries can cause pain and Range of Motion (ROM) limitation. The
      major objective of this study was to determine which cervical ROM limitation was
      accompanied with higher level of hearing loss. Methods: In this cross-sectional
      study, 42 volunteers (20 women and 22 men) with cervical spine injury and pain
      participated after giving their informed consent. Audiometry, tympanometry, and
      pure-tone threshold of individuals were taken in frequencies from 250 to 8000 Hz
      in all cases. The ROM limitation in flexion, extension and rotation was recorded.
      Results: About 53% of participants had bilateral hearing loss. In 40.48% (n=17)
      of cases, rotation to the left was limited. Flexion and extension motion were
      restricted on 23.8% (n=10) and 30.95% (n=13) of the participants, respectively.
      There was no statistically significant relationship between sex and hearing loss
      but a significant correlation was observed between hearing loss and ROM
      limitation of rotation to the left in men. Conclusion: According to the present
      study, the likelihood of hearing loss was high in patients with cervical left
      rotation limitation, and that the incidence of hearing loss following the
      cervical spine injuries was more in men. It seems that left Rotation limitation
      can be used as a predictor to diagnosis of hearing impairment following the
      cervical spine injuries (especially in men).

PMID- 29167730
TI  - ON THE BLOCK-SPARSITY OF MULTIPLE-MEASUREMENT VECTORS.
AB  - Based on the compressive sensing (CS) theory, it is possible to recover signals,
      which are either compressible or sparse under some suitable basis, via a small
      number of non-adaptive linear measurements. In this paper, we investigate
      recovering of block-sparse signals via multiple measurement vectors (MMVs) in the
      presence of noise. In this case, we consider one of the existing algorithms which
      provides a satisfactory estimate in terms of minimum mean-squared error but a non
      sparse solution. Here, the algorithm is first modified to result in sparse
      solutions. Then, further modification is performed to account for the unknown
      block sparsity structure in the solution, as well. The performance of the
      proposed algorithm is demonstrated by experimental simulations and comparisons
      with some other algorithms for the sparse recovery problem.

PMID- 29167729
TI  - Emotional Face Recognition in Children With Attention Deficit/Hyperactivity
      Disorder: Evidence From Event Related Gamma Oscillation.
AB  - Introduction: Children with attention-deficit/hyperactivity disorder (ADHD) have
      some impairment in emotional relationship which can be due to problems in
      emotional processing. The present study investigated neural correlates of early
      stages of emotional face processing in this group compared with typically
      developing children using the Gamma Band Activity (GBA). Methods: A total of 19
      children diagnosed with ADHD (Combined type) based on DSM-IV classification were
      compared with 19 typically developing children matched on age, gender, and IQ.
      The participants performed an emotional face recognition while their brain
      activities were recorded using an event-related oscillation procedure. Results:
      The results indicated that ADHD children compared to normal group showed a
      significant reduction in the gamma band activity, which is thought to reflect
      early perceptual emotion discrimination for happy and angry emotions (P<0.05).
      Conclusion: The present study supports the notion that individuals with ADHD have
      some impairments in early stage of emotion processing which can cause their
      misinterpretation of emotional faces.

PMID- 29167731
TI  - Purification and characterization of GAD65-specific monoclonal autoantibodies.
AB  - Autoantibodies against antigens expressed by insulin-producing beta cells are
      circulating in both healthy individuals and patients at risk of developing Type 1
      diabetes. Recent studies suggest that another set of antibodies (anti-idiotypic
      antibodies) exists in this antibody/antigen interacting network to regulate auto
      reactive responses. Anti-idiotypic antibodies may block the antigen-binding site
      of autoantibodies or inhibit autoantibody expression and secretion. The
      equilibrium between autoantibodies and anti-idiotypic antibodies plays a critical
      role in mediating or preventing autoimmunity. Herein, using GAD65/anti-GAD65
      autoantibodies as a model system, we aimed at establishing reliable approaches
      for purification of highly pure autoantibodies for the downstream investigation
      of molecular mechanisms underlying such a network.

PMID- 29167732
TI  - Blockchain protocols in clinical trials: Transparency and traceability of
      consent.
AB  - Clinical trial consent for protocols and their revisions should be transparent
      for patients and traceable for stakeholders. Our goal is to implement a process
      allowing the collection of patients' informed consent, which is bound to protocol
      revisions, storing and tracking the consent in a secure, unfalsifiable and
      publicly verifiable way, and enabling the sharing of this information in real
      time. For that, we will built a consent workflow using a rising technology called
      Blockchain. This is a distributed technology that brings a built-in layer of
      transparency and traceability. Additionally, it removes the need for third
      parties, and gives participative control to the peer-to-peer users. From a more
      general and prospective point of view, we believe Blockchain technology brings a
      paradigmatical shift to the entire clinical research field. We designed a Proof
      of-Concept protocol consisting of time-stamping each step of the patient's
      consent collection using Blockchain; thus archiving and historicising the consent
      through cryptographic validation in a securely unfalsifiable and transparent way.
      For each revision of the protocol, consent was sought again. We obtained a single
      document, in a standard open format, that accounted for the whole consent
      collection process: timestamped consent status with regards to each version of
      the protocol. This document cannot be corrupted, and can be checked on any
      dedicated public website. It should be considered as a robust proof of data. In
      the future, we think that the complex data flow of a clinical trial can be
      tracked using Blockchain. Moreover, a blockchain core functionality, named Smart
      Contract, can help prevent clinical trial events not to happen in the right
      chronological order: including patients before they consented or analysing case
      report forms data before freezing the database. This will help reaching
      reliability, security, and transparency, and could be a consistent step towards
      reproducibility.

PMID- 29167733
TI  - A 4-week, lifestyle-integrated, home-based exercise training programme elicits
      improvements in physical function and lean mass in older men and women: a pilot
      study.
AB  - BACKGROUND: Developing alternative exercise programmes that can alleviate certain
      barriers to exercise such as psychological, environmental or socio-economical
      barriers, but provide similar physiological benefits e.g. increases in muscle
      mass and strength, is of grave importance. This pilot study aimed to assess the
      efficacy of an unsupervised, 4-week, whole-body home-based exercise training
      (HBET) programme, incorporated into daily living activities, on skeletal muscle
      mass, power and strength. METHODS: Twelve healthy older volunteers (63+/-3 years,
      7 men: 5 women, BMI: 29+/-1 kg/m2) carried out the 4-week "lifestyle-integrated"
      HBET of 8 exercises, 3x12 repetitions each, every day. Before and after HBET, a
      number of physical function tests were carried out: unilateral leg extension 1-RM
      (one- repetition maximum), MVC (maximal voluntary contraction) leg extension,
      lower leg muscle power (via Nottingham Power Rig), handgrip strength and SPPBT
      (short physical performance battery test). A D 3-Creatine method was used for
      assessment of whole-body skeletal muscle mass, and ultrasound was used to measure
      the quadriceps cross-sectional area (CSA) and vastus lateralis muscle thickness.
      RESULTS: Four weeks HBET elicited significant (p<0.05) improvements in leg muscle
      power (276.7+/-38.5 vs. 323.4+/-43.4 W), maximal voluntary contraction (60
      degrees : 154.2+/-18.4 vs. 168.8+/-15.2 Nm, 90 degrees : 152.1+/-10.5 vs. 159.1+/
      11.4 Nm) and quadriceps CSA (57.5+/-5.4 vs. 59.0+/-5.3 cm 2), with a trend for an
      increase in leg strength (1-RM: 45.7+/-5.9 vs. 49.6+/-6.0 kg, P=0.08). This was
      despite there being no significant differences in whole-body skeletal muscle
      mass, as assessed via D 3-Creatine. CONCLUSIONS: This study demonstrates that
      increases in multiple aspects of muscle function can be achieved in older adults
      with just 4-weeks of "lifestyle-integrated" HBET, with a cost-effective means.
      This training mode may prove to be a beneficial alternative for maintaining
      and/or improving muscle mass and function in older adults.

PMID- 29167734
TI  - Treatment of chronic telogen effluvium with oral minoxidil: A retrospective
      study.
AB  - Background: Chronic telogen effluvium (CTE) may be primary or secondary to
      various causes, including drug reaction, nutritional deficiency and female
      pattern hair loss (FPHL).  Oral minoxidil stimulates hair growth, and topical
      minoxidil is used in the treatment of FPHL and male androgenetic alopecia.
      minoxidil has not been used to treat CTE. This study aimed to assess the
      treatment of CTE with once daily oral minoxidil. Methods: Women with a diagnosis
      of CTE based on >6 month history of increased telogen hair shedding, no visible
      mid frontal scalp hair loss (Sinclair stage 1) and no hair follicle
      miniaturization on scalp biopsy were treated with once daily oral minoxidil. 
      Hair shedding scores (HSS) at baseline, 6 and 12 months were analysed using the
      Wilcoxon rank sum test for pair-wise comparisons. Results: Thirty-six women were
      treated with oral minoxidil (range, 0.25-2.5 mg) daily for 6 months.  Mean age
      was 46.9 years (range 20-83), HSS at baseline was 5.64, and duration of diagnosis
      was 6.55 years (range 1-27).  There was a reduction in mean HSS scores from
      baseline to 6 months of 1.7 (p<0.001) and baseline to 12 months of 2.58
      (p<0.001). Five women who described trichodynia at baseline, noted improvement or
      resolution within 3 months.  Mean change in blood pressure was minus 0.5 mmHg
      systolic and plus 2.1 mmHg diastolic.  Two patients developed transient postural
      dizziness that resolved with continued treatment.  One patient developed ankle
      oedema.  Thirteen women developed facial hypertrichosis.  For 6 patients this was
      mild and did not require treatment; 4 had waxing of their upper lip or forehead;
      3 had laser hair removal.  No patients developed any haematological abnormality. 
      All 36 women completed 12 months of treatment. Conclusions: Once daily oral
      minoxidil appears to reduce hair shedding in CTE.  Placebo controlled studies are
      recommended to further assess this response.

PMID- 29167735
TI  - A review of data sharing statements in observational studies published in the
      BMJ: A cross-sectional study.
AB  - In order to understand the current state of data sharing in observational
      research studies, we reviewed data sharing statements of observational studies
      published in a general medical journal, the British Medical Journal. We found
      that the majority (63%) of observational studies published between 2015 and 2017
      included a statement that implied that data used in the study could not be
      shared. If the findings of our exploratory study are confirmed, room for
      improvement in the sharing of real-world or observational research data exists.

PMID- 29167736
TI  - On the interpretability and computational reliability of frequency-domain Granger
      causality.
AB  - This Correspondence article is a comment which directly relates to the paper "A
      study of problems encountered in Granger causality analysis from a neuroscience
      perspective" ( Stokes and Purdon, 2017). We agree that interpretation issues of
      Granger causality (GC) in neuroscience exist, partially due to the historically
      unfortunate use of the name "causality", as described in previous literature. On
      the other hand, we think that Stokes and Purdon use a formulation of GC which is
      outdated (albeit still used) and do not fully account for the potential of the
      different frequency-domain versions of GC; in doing so, their paper dismisses GC
      measures based on a suboptimal use of them. Furthermore, since data from
      simulated systems are used, the pitfalls that are found with the used formulation
      are intended to be general, and not limited to neuroscience. It would be a pity
      if this paper, even if written in good faith, became a wildcard against all
      possible applications of GC, regardless of the large body of work recently
      published which aims to address faults in methodology and interpretation. In
      order to provide a balanced view, we replicate the simulations of Stokes and
      Purdon, using an updated GC implementation and exploiting the combination of
      spectral and causal information, showing that in this way the pitfalls are
      mitigated or directly solved.

PMID- 29167737
TI  - Make researchers revisit past publications to improve reproducibility.
AB  - Scientific irreproducibility is a major issue that has recently increased
      attention from publishers, authors, funders and other players in the scientific
      arena.  Published literature suggests that 50-80% of all science performed is
      irreproducible.  While various solutions to this problem have been proposed, none
      of them are quick and/or cheap.  Here, we propose one way of reducing scientific
      irreproducibility by asking authors to revisit their previous publications and
      provide a commentary after five years. We believe that this measure will alert
      authors not to over sell their results and will help with better planning and
      execution of their experiments.  We invite scientific journals to adapt this
      proposal immediately as a prerequisite for publishing.

PMID- 29167738
TI  - Updated mtCOI reference dataset for the Bemisia tabaci species complex.
AB  - Members of the whitefly Bemisia tabaci species complex cause millions of dollars
      of damage globally and are considered one of the world's most invasive species.
      They are capable of causing extensive damage to major vegetable, grain legume and
      fiber crops. All member of the species complex are morphologically identical
      therefore, data from the partial mitochondrial cytochrome oxidase subunit I
      (mtCOI) gene sequence has been used to identify the various species. The current
      reference dataset that is widely used is found on the CSIRO data portal. However,
      the reference set stored on the CSIRO data does not include newly added sequences
      (2013-2017), therefore an updated reference dataset is needed.  All mtCOI data
      for the Bemisia tabaci species complex were downloaded on 22 May 2017 from
      GenBank and after quality checking, a dataset of 1,071 unique sequences and 696
      base pairs was generated (https://doi.org/10.6084/m9.figshare.5437420.v1).

PMID- 29167739
TI  - Measuring evolutionary rates of proteins in a structural context.
AB  - We describe how to measure site-specific rates of evolution in protein-coding
      genes and how to correlate these rates with structural features of the expressed
      protein, such as relative solvent accessibility, secondary structure, or weighted
      contact number. We present two alternative approaches to rate calculations, one
      based on relative amino-acid rates and the other based on site-specific codon
      rates measured as dN/dS. In addition to describing the specific analysis
      protocols we recommend, we also provide a code repository containing scripts to
      facilitate these kinds of analyses.

PMID- 29167740
TI  - Prenatal maternal plasma DNA screening for cystic fibrosis: A computer modelling
      study of screening performance.
AB  - Background: Prenatal cystic fibrosis (CF) screening is currently based on
      determining the carrier status of both parents. We propose a new method based
      only on the analysis of DNA in maternal plasma. Methods: The method relies on the
      quantitative amplification of the CF gene to determine the percentage of DNA
      fragments in maternal plasma at targeted CF mutation sites that carry a CF
      mutation. Computer modelling was carried out to estimate the distributions of
      these percentages in pregnancies with and without a fetus affected with CF. This
      was done according to the number of DNA fragments counted and fetal fraction,
      using the 23 CF mutations recommended by the American College of Medical Genetics
      for parental carrier testing. Results: The estimated detection rate (sensitivity)
      is 70% (100% of those detected using the 23 mutations), the false-positive rate
      0.002%, and the odds of being affected given a positive screening result 14:1,
      compared with 70%, 0.12%, and 1:3, respectively, with current prenatal screening
      based on parental carrier testing. Conclusions: Compared with current screening
      practice based on parental carrier testing, the proposed method would
      substantially reduce the number of invasive diagnostic procedures (amniocentesis
      or chorionic villus sampling) without reducing the CF detection rate. The
      expected advantages of the proposed method justify carrying out the necessary
      test development for use in a clinical validation study.

PMID- 29167742
TI  - The effect of natural sounds on the anxiety of patients undergoing coronary
      artery bypass graft surgery.
AB  - Background: This study aims to investigate the effect of natural sounds on the
      anxiety of patients undergoing coronary artery bypass graft surgery (CABG).
      Methods: In this clinical trial, 90 patients, who were candidates for CABG in an
      urban area of Iran, were selected and randomly assigned to intervention and
      control groups by the minimization method. In the intervention group, natural
      sounds were broadcast through headphones for 30 min. In the control group,
      headphones connected to a silent device were used. The research instruments were
      a demographic questionnaire and the Spielberger State-Trait Anxiety Inventory
      (STAI). These were used before the intervention, 30 min after the music, and
      before the surgery in the waiting room for both groups. Data was analyzed using
      SPSS software. Results: The mean anxiety level of the intervention group has been
      found to be significantly lower than that of the control group half an hour after
      the intervention as well as in the waiting room in the preoperative period (p =
      0.001). Moreover, the mean anxiety of the intervention group decreases, while it
      increases for the control group over time (p < 0.001). Conclusion: Natural sounds
      can be used as a non-pharmacological way to reduce the anxiety of patients
      undergoing CABG. Trial registration: IRCT2017011723190N3, Registered 1 March
      2017.

PMID- 29167741
TI  - Experimental autoimmune encephalomyelitis from a tissue energy perspective.
AB  - Increasing evidence suggests a key role for tissue energy failure in the
      pathophysiology of multiple sclerosis (MS). Studies in experimental autoimmune
      encephalomyelitis (EAE), a commonly used model of MS, have been instrumental in
      illuminating the mechanisms that may be involved in compromising energy
      production. In this article, we review recent advances in EAE research focussing
      on factors that conspire to impair tissue energy metabolism, such as tissue
      hypoxia, mitochondrial dysfunction, production of reactive oxygen/nitrogen
      species, and sodium dysregulation, which are directly affected by energy
      insufficiency, and promote cellular damage. A greater understanding of how
      inflammation affects tissue energy balance may lead to novel and effective
      therapeutic strategies that ultimately will benefit not only people affected by
      MS but also people affected by the wide range of other neurological disorders in
      which neuroinflammation plays an important role.

PMID- 29167743
TI  - Prevalence and characteristics of ST131 clone among unselected clinical
      Escherichia coli in a Chinese university hospital.
AB  - Background: Escherichia coli clinical sequence type 131 (ST131) has emerged as an
      extensively antimicrobial resistant E. coli clonal group in recent years
      throughout the world. The aim of this study was to investigate the prevalence and
      molecular characteristics of ST131 among unselected E. coli clinical isolates in
      a Chinese university hospital. Methods: Seven hundred consecutive E. coli
      isolates were collected at a Chinese university hospital between 2014 and 2015.
      Isolates belonging to ST131 were identified by PCR and multilocus sequence typing
      (MLST), and then characterized for antibiotic resistance, CTX-M-type extended
      spectrum beta-lactamase genes, fluoroquinolone resistance genes, O types,
      phylogenetic groups, virulence factors and PFGE patterns. Results: Overall, 83
      (11.6%) isolates were identified as ST131 group. The H30 lineage accounted for 53
      (63.9%) of the ST131 isolates, including 13 H30-Rx and 40 H30 non-Rx. The
      remaining 30 isolates belonged to H41 lineage. Two O types were identified in
      this study: O25b (66.3%) and O16 (33.7%). Compared with O25b-B2-ST131 isolates,
      O16-B2-ST131 isolates harbored less virulence factors of adhesins. ST131 H30 Rx
      isolates had significantly higher virulence score than those of other isolates.
      O16-B2-ST131 isolates were shown to have a lower resistance to quinolones than
      O25b-B2-ST131 isolates. 5 nonsynonymous mutations (GyrA S83 L, D87N, ParC S80I,
      E84V and ParE I529L) were strongly associated with ST131 H30 and O25b isolates.
      Results of PFGE demonstrated that these isolates were classified into 68
      pulsotypes and these subtypes were grouped into 23 different PFGE clusters using
      70% similarity cut-off value. Conclusions: This is the first study to reveal the
      prevalence and molecular characteristic of ST131 clonal group among consecutive
      clinical E. coli isolates in China. Our findings demonstrated that ST131 lineage
      accounts for a small proportion of clinical E. coli isolates in China, which
      included two major groups: O25b-B2-ST131 and O16-B2-ST131. Our results implies
      that O16-B2-ST131 subclone may be an important type of E. coli ST 131 in China,
      which suggests that future studies should not ignore such clone in this country.

PMID- 29167744
TI  - Feasibility of an incentive scheme to promote active travel to school: a pilot
      cluster randomised trial.
AB  - Background: In Great Britain, 19% of trips to primary school within 1 mile, and
      62% within 1-2 miles, are by car. Active travel to school (ATS) offers a
      potential source of moderate-to-vigorous physical activity (MVPA). This study
      tested the feasibility of an intervention to promote ATS in 9-10 year olds and
      associated trial procedures. Methods: A parallel cluster randomised pilot trial
      was conducted over 9 weeks in two schools from a low-income area in northeast
      England. Measures included daily parental ATS reports (optionally by SMS) and
      child ATS reports, as well as accelerometry (ActiGraph GT3X+). At baseline, all
      children were asked to wear the accelerometer for the same week; in the post
      randomisation phase, small subsamples were monitored each week. In the 2 weeks
      when a child wore the accelerometer, parents also reported the start and finish
      times of the journey to school. The intervention consisted of a lottery-based
      incentive scheme; every ATS day reported by the parent, whether by paper or SMS,
      corresponded to one ticket entered into a weekly L5 voucher draw. Before each
      draw session, the researcher prepared the tickets and placed them into an opaque
      bag, from which one was randomly picked by the teacher at the draw session.
      Results: Four schools replied positively (3.3%, N = 123) and 29 participants were
      recruited in the two schools selected (33.0%, N = 88). Participant retention was
      93.1%. Most materials were returned on time: accelerometers (81.9%), parental
      reports (82.1%) and child reports (97.9%). Draw sessions lasted on average 15.9
      min (IQR 10-20) and overall session attendance was 94.5%. Parent-child report
      agreement regarding ATS was moderate (k = 0.53, CI 95% 0.45; 0.60). Differences
      in minutes of accelerometer-assessed MVPA between parent-reported ATS and non-ATS
      trips were assessed during two timeframes: during the journey to school based on
      the times reported by the parent (U = 390.5, p < 0.05, 2.46 (n = 99) vs 0.76 (n =
      13)) and in the hour before classes (U = 665.5, p < 0.05, 4.99 (n = 104) vs 2.55
      (n = 19)). Differences in MVPA minutes between child-reported ATS and non-ATS
      trips were also significant for each of the timeframes considered (U = 596.5, p <
      0.05, 2.40 (n = 128) vs 0.81 (n = 15) and U = 955.0, p < 0.05, 4.99 (n = 146) vs
      2.59 (n = 20), respectively). Conclusions: Data suggest the feasibility of an ATS
      incentive scheme and of most trial procedures. School recruitment stood out as
      requiring further piloting. Trial registration: ClinicalTrials.gov: NCT02282631.
      Registered 5th September 2014.

PMID- 29167745
TI  - The use of smartphones to influence lifestyle changes in overweight and obese
      youth with congenital heart disease: a single-arm study: Pilot and feasibility
      study protocol: Smart Heart Trial.
AB  - Background: Both obesity and congenital heart disease (CHD) are risk factors for
      the long-term cardiovascular health of children and adolescents. The addition of
      smart mobile technology to conventional lifestyle counseling for weight
      management offers great potential to appeal to technologically literate youth and
      can address a large geographical area with minimal burden to participants. This
      pilot study seeks to examine the influence of a 1-year lifestyle intervention on
      nutrition and physical activity-related health outcomes in overweight or obese
      children and adolescents with CHD. Methods: This is a pilot and feasibility study
      which utilizes a single-arm, prospective design with a goal to recruit 40
      overweight and obese patients. The feasibility metrics will evaluate the
      integrity of the study protocol, data collection and questionnaires, recruitment
      and consent, and acceptability of the intervention protocol and primary outcome
      measures. The primary clinical outcome metrics are anthropometry, body
      composition, and cardiorespiratory exercise capacity. The secondary clinical
      metrics include quality of life, nutrition and physical activity behavior, lung
      and muscle function, and cardio-metabolic risk factors. Outcomes are assessed at
      baseline, 6 months, and 1 year. To date, a total of 36 children and youth (11
      girls), aged 7-17 years (mean = 14.4 years), have commenced the intervention.
      Recruitment for the study was initiated in June 2012 and is currently ongoing.
      Discussion: The information provided in this paper is intended to help
      researchers and health professionals with the development and evaluation of
      similar lifestyle intervention programs. Since the application of smartphones to
      pediatric cardiac health and obesity management is a novel approach, and
      continued research in this area is warranted, this paper may serve as a
      foundation for further exploration of this health frontier and inform the
      development of a broader strategy for obesity management in pediatric cardiology.
      Trial registration: This pilot study was retrospectively registered at the
      www.ClinicalTrials.gov registry as NCT02980393 in November 2016, with the study
      commencing in May 2012. Study protocol version 15OCT2014.

PMID- 29167746
TI  - Comparison of in vivo antibacterial and antithrombotic activities of two types of
      pulmonary artery catheters in pig.
AB  - Background: During pulmonary artery catheter (PAC) implantation, inaccurate
      measurements of hemodynamic parameters due to infection or thrombosis of PAC can
      result in severe complications. Method: In order to develop a new PAC material,
      we evaluated the antibacterial and antithrombotic activities of the two types of
      PAC (Swan Ganz catheter and prototype catheter) in 14 pigs. Results: In the 3-day
      group, bacterial infection rate was not different between the two types of PAC.
      In the 7-day group, bacterial infection rate of the prototype catheter was twice
      as elevated as that of the Swan-Ganz catheter. In the 3-day group, thrombus
      formation rate of the prototype catheter was twice as elevated as that of the
      Swan-Ganz catheter. In the 7-day group, thrombus formation rate was the same for
      the two types of PAC. Conclusion: Here, we report an experimental pig model that
      confirms differences in antibacterial and antithrombotic activities.

PMID- 29167749
TI  - Introduction: 2017 Taiwan Association of Thoracic & Cardiovascular Surgery.

PMID- 29167747
TI  - Health benefits of late-onset metformin treatment every other week in mice.
AB  - Chronic 1% metformin treatment is nephrotoxic in mice, but this dose may
      nonetheless confer health benefits if given intermittently rather than
      continuously. Here, we examined the effects of 1% metformin given every-other
      week (EOW) or two consecutive weeks per month (2WM) on survival of 2-year-old
      male mice fed standard chow. EOW and 2WM mice had comparable life span compared
      with control mice. A significant reduction in body weight within the first few
      weeks of metformin treatment was observed without impact on food consumption and
      energy expenditure. Moreover, there were differences in the action of metformin
      on metabolic markers between the EOW and 2WM groups, with EOW metformin
      conferring greater benefits. Age-associated kidney lesions became more pronounced
      with metformin, although without pathological consequences. In the liver,
      metformin treatment led to an overall reduction in steatosis and was accompanied
      by distinct transcriptomic and metabolomic signatures in response to EOW versus
      2WM regimens. Thus, the absence of adverse outcomes associated with chronic,
      intermittent use of 1% metformin in old mice has clinical translatability into
      the biology of aging in humans.

PMID- 29167750
TI  - Dysregulation of the miR-146a-Smad4 axis impairs osteogenesis of bone mesenchymal
      stem cells under inflammation.
AB  - Osteoporosis is a common disease that affects patient quality of life, especially
      among the elderly population. Although inflammation contributes significantly to
      osteoporosis, the underlying mechanism is unclear. In this study, we found that
      tumor necrosis factor (TNF)-alpha, an inflammatory environment mimic, inhibits
      osteogenesis of bone mesenchymal stem cells (BMSCs), induces miR-146a and
      decreases Smad4. Moreover, overexpression of miR-146a inhibited the osteogenic
      ability of BMSCs, whereas blocking miR-146a partially rescued the osteogenesis
      deficiency under TNF-alpha treatment. Molecularly, miR-146a decreased Smad4
      expression at the protein level by binding to an element located in the Smad4 3'
      untranslated region, and restoration of Smad4 reversed the inhibitory effects of
      miR-146a on osteogenesis. Together, our results showed that the inflammatory
      environment mimic TNF-alpha inhibits osteogenesis via upregulation of miR-146a
      and subsequent downregulation of Smad4, thus suggesting that therapeutic
      manipulation of miR-146a maybe a potential strategy to improve osteogenesis in
      the context of osteoporosis.

PMID- 29167751
TI  - Diffusion Tensor Imaging in an Infant Undergoing Functional Hemispherectomy: A
      Surgical Aid.
AB  - Hemispherectomy is a highly effective treatment option for children with severe,
      unilateral, medically refractory epilepsy. Many patients undergoing
      hemispherectomy are younger patients with dysmorphic brains, making accomplishing
      a complete disconnection challenging due to anatomic distortion, even with the
      aid of intraoperative navigation. Diffusion tensor imaging (DTI) has been
      proposed as a valuable imaging adjunct perioperatively to help guide surgeons
      intraoperatively, as well as for post-surgical evaluation and confirmation of
      complete hemispheric disconnection. We present a case of an infant with Otoharra
      syndrome and hemimegencephaly who underwent a functional hemispherectomy for
      treatment of severe, refractory seizures. We demonstrate how DTI was utilized
      both pre-, intra-, and postoperatively to help plan, guide, and confirm surgical
      disconnection. The application of exquisite DTI for this child led to her being
      seizure-free, which is a life-changing event with long-lasting benefits and will
      become even more critical as we now perform these disconnection procedures with a
      more minimally invasive approach.

PMID- 29167748
TI  - Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages
      in culture cells.
AB  - Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa
      which affects both ruminants and humans. RVF causes serious damage to the
      livestock industry and is also a threat to public health. The Rift Valley fever
      virus has a segmented negative-stranded RNA genome consisting of Large (L)-,
      Medium (M)-, and Small (S)-segments. The live-attenuated MP-12 vaccine is
      immunogenic in livestock and humans, and is conditionally licensed for veterinary
      use in the U.S. The MP-12 strain encodes 23 mutations (nine amino acid
      substitutions) and is attenuated through a combination of mutations in the L-, M
      , and S-segments. Among them, the M-U795C, M-A3564G, and L-G3104A mutations
      contribute to viral attenuation through the L- and M-segments. The M-U795C, M
      A3564G, L-U533C, and L-G3750A mutations are also independently responsible for
      temperature-sensitive (ts) phenotype. We hypothesized that a serial passage of
      the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP
      12 vaccine and recombinant rMP12-DeltaNSs16/198 were serially passaged 25 times.
      Droplet digital PCR analysis revealed that the reversion occurred at L-G3750A
      during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M
      A3564G and L-U533C of rMP12-DeltaNSs16/198 in Vero cells. Reversion mutations
      were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with
      encephalitis. This study characterized genetic stability of the MP-12 vaccine and
      the potential risk of reversion mutation at the L-G3750A ts mutation after
      excessive viral passages in culture cells.

PMID- 29167752
TI  - A Prospective Study of Distal Metatarsal Chevron Osteotomies with K-Wire
      Fixations to Treat Hallux Valgus Deformities.
AB  - Introduction Hallux valgus is one of the most common forefoot deformities
      worldwide. Females are affected more often than males. The three most common
      clinical symptoms are the painful bunion, transfer metatarsalgia, and hammer or
      claw toes. Methods This case series consisted of 20 patients who had chevron
      osteotomy from January 2015 to January 2016. The clinical assessment was measured
      by The American Orthopedic Foot and Ankle Score (AOFAS), and radiologic
      assessment was determined by preoperative and postoperative hallux valgus angle
      (HVA) and intermetatarsal angle (IMA). Results The patients' mean age was 56
      years. Out of 20 patients, 19 were female, and one was male. The mean AOFAS
      improved from 51 preoperatively to 82 postoperatively. The HVA improved from 26
      degrees  preoperatively to 14 degrees . There were five complications including
      four Kirschner (K)-wire complications. Conclusion Distal chevron osteotomy is a
      reliable and time-tested procedure. The K-wire fixation has a relatively high
      complication rate. We planned to use other methods of fixation and then compared
      them with K-wires fixation results for future studies.

PMID- 29167754
TI  - A mass that has no (EBUS) echo.
AB  - We report findings for a patient that underwent endobronchial ultrasound (EBUS)
      guided transbronchial needle aspiration (TBNA) for diagnostic purposes after an
      abnormal chest CT. The patient initially presented with cough and shortness of
      breath. Chest CT revealed a 6 cm soft tissue mass with mildly enlarged right
      hilar lymph nodes (LNs) and a small right sided pleural effusion. Based on these
      radiologic findings, the patient underwent an EBUS guided FNA of the mass. To our
      surprise, the mass was hypoechoic by EBUS and on aspiration, the syringe filled
      with yellow fluid. This finding in combination with a re-review of the CT scans
      with a special focus on the Hounsfield Units of the lesion confirmed the
      diagnosis of a mediastinal bronchogenic cyst. This case demonstrates the role of
      Hounsfield units in analyzing mediastinal masses and highlights the effectiveness
      of EBUS guided TBNA in diagnosis and treatment of bronchogenic cysts.

PMID- 29167753
TI  - Homology Modeling of Human Concentrative Nucleoside Transporters (hCNTs) and
      Validation by Virtual Screening and Experimental Testing to Identify Novel hCNT1
      Inhibitors.
AB  - Objective: The nucleoside transporter family is an emerging target for cancer,
      viral and cardiovascular diseases. Due to the difficulty in the expression,
      isolation and crystallization of membrane proteins, there is a lack of structural
      information on any of the mammalian and for that matter the human proteins. Thus
      the objective of this study was to build homology models for the three cloned
      concentrative nucleoside transporters hCNT1, hCNT2 and hCNT3 and validate them
      for screening towards the discovery of much needed inhibitors and probes.
      Methods: The recently reported crystal structure of the Vibrio cholerae
      concentrative nucleoside transporter (vcCNT), has satisfactory similarity to the
      human CNT orthologues and was thus used as a template to build homology models of
      all three hCNTs. The Schrodinger modeling suite was used for the exercise.
      External validation of the homology models was carried out by docking a set of
      recently reported known hCNT1 nucleoside class inhibitors at the putative binding
      site using induced fit docking (IDF) methodology with the Glide docking program.
      Then, the hCNT1 homology model was subsequently used to conduct a virtual
      screening of a 360,000 compound library, and 172 compounds were obtained and
      biologically evaluated for hCNT 1, 2 and 3 inhibitory potency and selectivity.
      Results: Good quality homology models were obtained for all three hCNTs as
      indicated by interrogation for various structural parameters and also external
      validated by docking of known inhibitors. The IDF docking results showed good
      correlations between IDF scores and inhibitory activities; particularly for
      hCNT1. From the top 0.1% of compounds ranked by virtual screening with the hCNT1
      homology model, 172 compounds selected and tested for against hCNT1, hCNT2 and
      hCNT3, yielded 14 new inhibitors (hits) of (i.e., 8% success rate). The most
      active compound exhibited an IC50 of 9.05 MUM, which shows a greater than 25-fold
      higher potency than phlorizin the standard CNT inhibitor (IC50 of 250 MUM).
      Conclusion: We successfully undertook homology modeling and validation for all
      human concentrative nucleoside transporters (hCNT 1, 2 and 3). The proof-of
      concept that these models are promising for virtual screening to identify potent
      and selective inhibitors was also obtained using the hCNT1 model. Thus we
      identified a novel potent hCNT1 inhibitor that is more potent and more selective
      than the standard inhibitor phlorizin. The other hCNT1 hits also mostly exhibited
      selectivity. These homology models should be useful for virtual screening to
      identify novel hCNT inhibitors, as well as for optimization of hCNT inhibitors.

PMID- 29167755
TI  - Infrared thermography of welding zones produced by polymer extrusion additive
      manufacturing.
AB  - In common thermoplastic additive manufacturing (AM) processes, a solid polymer
      filament is melted, extruded though a rastering nozzle, welded onto neighboring
      layers and solidified. The temperature of the polymer at each of these stages is
      the key parameter governing these non-equilibrium processes, but due to its
      strong spatial and temporal variations, it is difficult to measure accurately.
      Here we utilize infrared (IR) imaging - in conjunction with necessary reflection
      corrections and calibration procedures - to measure these temperature profiles of
      a model polymer during 3D printing. From the temperature profiles of the printed
      layer (road) and sublayers, the temporal profile of the crucially important weld
      temperatures can be obtained. Under typical printing conditions, the weld
      temperature decreases at a rate of approximately 100  degrees C/s and remains
      above the glass transition temperature for approximately 1 s. These measurement
      methods are a first step in the development of strategies to control and model
      the printing processes and in the ability to develop models that correlate
      critical part strength with material and processing parameters.

PMID- 29167756
TI  - An innovative approach for serial injection in marginal vein and blood collection
      from auricular artery in New Zealand white Rabbit.
AB  - Serial injection into marginal vein and blood collection through auricular artery
      in New Zealand white Rabbit (Oryctolagus cuniculus) is an important procedure for
      various types of experimental studies. Limitations of the existing methods for
      serial injection and blood collection includes complex procedures, causes
      considerable discomfort to rabbits, whole blood samples obtained are highly prone
      to hemolysis and lastly detailed protocol is not available in the literature.
      Approximately 10 min before commencement of the experiment, a local anesthetic
      cream was applied over the right and left ear lobes. The skin at the site of
      sample collection and injection was prepared by shaving the area on both ears and
      wiping it with alcohol swab. Once prepared, a 26 GA (BD Neoflon) intravenous
      cannula was inserted into the marginal vein of the ear and secured with an
      adhesive plaster. In the other ear, a 24 GA (BD Neoflon) intravenous cannula was
      placed in the auricular/central artery and secured with an adhesive plaster. The
      novel and refined method described here has been standardized and found to be
      reliable. The samples obtained using this method is not susceptible to hemolysis
      and hence we recommend this method for serial injection and blood collection in
      rabbits. *Easy to perform*Not prone to hemolysis*Detailed methodology described.

PMID- 29167758
TI  - High-throughput microarray for antimicrobial susceptibility testing.
AB  - We describe the development of a novel, high-throughput, nano-scale microarray
      platform for antimicrobial susceptibility testing (AST). The platform allows to
      process 480 samples at 50 nL volume on a single chip, analyze by fluorescence
      read-out with an easy dunk-and-rinse step, and the ability to process multiple
      samples and chips simultaneously. We demonstrate the applicability of this chip
      for culturing community acquired methicillin resistant Staphylococcus aureus (CA
      MRSA), and perform AST against clinical isolates of CA-MRSA. The chip platform
      holds promise for an impact in microbial biotechnology as an attractive high
      throughput, lower sample volume and quicker alternative to conventional AST such
      as the traditional broth microdilution or the newer automated systems.

PMID- 29167757
TI  - Amino acid catabolism-directed biofuel production in Clostridium sticklandii: An
      insight into model-driven systems engineering.
AB  - Model-driven systems engineering has been more fascinating process for the
      microbial production of biofuel and bio-refineries in chemical and pharmaceutical
      industries. Genome-scale modeling and simulations have been guided for metabolic
      engineering of Clostridium species for the production of organic solvents and
      organic acids. Among them, Clostridium sticklandii is one of the potential
      organisms to be exploited as a microbial cell factory for biofuel production. It
      is a hyper-ammonia producing bacterium and is able to catabolize amino acids as
      important carbon and energy sources via Stickland reactions and the development
      of the specific pathways. Current genomic and metabolic aspects of this bacterium
      are comprehensively reviewed herein, which provided information for learning
      about protein catabolism-directed biofuel production. It has a metabolic
      potential to drive energy and direct solventogenesis as well as acidogenesis from
      protein catabolism. It produces by-products such as ethanol, acetate, n-butanol,
      n-butyrate and hydrogen from amino acid catabolism. Model-driven systems
      engineering of this organism would improve the performance of the industrial
      sectors and enhance the industrial economy by using protein-based waste in
      environment-friendly ways.

PMID- 29167759
TI  - Study on bioremediation of Lead by exopolysaccharide producing metallophilic
      bacterium isolated from extreme habitat.
AB  - Lead released from manufacturing factories, recycling plants, automobile company
      and landfill leachate is abundantly found in wastewater. An efficient
      bioremediating agent for lead removal from wastewater is expected to ease the
      ever increasing problem. The present study reports Pseudomonas sp. W6 isolated
      from extreme habitat of hot water spring of North-East India evaluated for its
      Lead biosorption property. The bacterium showed capacity to resist 1.0 mM lead in
      both solid and liquid minimal media. Epifluorescence microscopy reveal the
      viability of bacterial cells under metal stress condition. ICP-MS analysis
      revealed 65% and 61.2% removal of lead from the Synthetic Bangladesh Ground Water
      medium in batch culture and column study respectively which was higher when
      compared to biosorption capacity of P. aeruginosa MTCC2474, P. alcaligenes MJ7
      from forest soil and P. ficuserectae PKRS11 from uranium rich soil.
      Exopolysaccharide released by the isolate which influenced biosorption revealed
      the presence of ligands assayed using microbial hydrophobicity and FTIR. The
      extremophilic isolate is proposed as a choice for efficient bioremediation of
      lead contaminated wastewater.

PMID- 29167760
TI  - Sarcomatoid renal cell carcinoma: genomic insights from sequencing of matched
      sarcomatous and carcinomatous components.

PMID- 29167761
TI  - European Thyroid Association Guidelines for Ultrasound Malignancy Risk
      Stratification of Thyroid Nodules in Adults: The EU-TIRADS.
AB  - Thyroid ultrasound (US) is a key examination for the management of thyroid
      nodules. Thyroid US is easily accessible, noninvasive, and cost-effective, and is
      a mandatory step in the workup of thyroid nodules. The main disadvantage of the
      method is that it is operator dependent. Thyroid US assessment of the risk of
      malignancy is crucial in patients with nodules, in order to select those who
      should have a fine needle aspiration (FNA) biopsy performed. Due to the pivotal
      role of thyroid US in the management of patients with nodules, the European
      Thyroid Association convened a panel of international experts to set up European
      guidelines on US risk stratification of thyroid nodules. Based on a review of the
      literature and on the American Association of Clinical Endocrinologists, American
      Thyroid Association, and Korean guidelines, the panel created the novel European
      Thyroid Imaging and Reporting Data System, called EU-TIRADS. This comprises a
      thyroid US lexicon; a standardized report; definitions of benign and low-,
      intermediate-, and high-risk nodules, with the estimated risks of malignancy in
      each category; and indications for FNA. Illustrated by numerous US images, the EU
      TIRADS aims to serve physicians in their clinical practice, to enhance the
      interobserver reproducibility of descriptions, and to simplify communication of
      the results.

PMID- 29167763
TI  - Questionnaire-based Prevalence of Food Insecurity in Iran: A Review Article.
AB  - Background: Data on the questionnaire-based prevalence of food insecurity are
      needed to develop food and nutrition security studies and policies. The present
      study aimed to assess the questionnaire-based prevalence of food insecurity in
      Iran. Methods: A systematic search of cross-sectional studies were conducted on
      databases including PubMed, Google Scholar, Scopus, Magiran, Iranmedex, SID and
      Medlib up to 29 Oct 2015. Estimation of food insecurity prevalence was according
      to the instruments including 9-items-HFIAS, 18 and 6-items USDA (US-HFSSM) and
      Radimer/Cernel food security questionnaires. Pooled effect was estimated using
      random-effect model and heterogeneity was assessed by Cochran's Q and I2 tests.
      Results: Thirteen articles included in the study based on screening and
      assessment of eligibility. The questionnaire-based prevalence of food insecurity
      was 49.2% (CI95%: 43.8-54.6). The according to sub-groups analysis, the food
      insecurity without and with hunger was 29.6% (CI95%: 25.7-33.6) and 19.2% (CI95%:
      16-22.3), respectively. Conclusion: The about half of the population were food
      insecure. The food insecurity without hunger was more than the food insecurity
      with hunger. An ongoing food insecurity assessment system is needed to support
      evidence-informed policy and to plan interventions to increase the food security
      in different areas.

PMID- 29167762
TI  - LncRNA Expression in CD4+ T Cells in Neurosyphilis Patients.
AB  - Recent studies have shown that several long noncoding RNAs (lncRNAs) are involved
      in regulating the immune response to cope with pathogenic invasion. To date, the
      roles of lncRNAs in the CD4+ T cell response to Treponema pallidum (T. pallidum)
      infection in neurosyphilis patients remain unknown. The mRNA and lncRNA
      expression profiles of CD4+ T cells that were isolated from neurosyphilis
      patients and healthy controls were analyzed by microarray. A total of 2258
      lncRNAs and 1728 mRNAs were identified as over-expressed or under-expressed,
      respectively (fold change > 1.5) in the CD4+ T cells of neurosyphilis patients
      compared to the healthy controls. The lncRNA-mRNA co-expression network showed
      that 59 lncRNAs showed significant differences along with significantly different
      mRNAs. Among the 59 gene pairs, the LOC79999 mRNA was positively correlated with
      the RP11-160E2.16, RP11-160E2.11, and RP11-160E2.19 lncRNAs, and the NKX1-1 mRNA
      was positively correlated with the RP11-1398P2.1, RP11-160E2.19, and XLOC_003422
      lncRNAs. The following five mRNAs were correlated with two differential lncRNAs:
      DUSP16, AP000349.1, FAM115C, TIMM8A, and SMCHD1. Gene Ontology (GO) analysis
      revealed that the differentially expressed coding genes were mainly involved in
      biological processes and the top 4 terms that associated with above-mentioned
      differentially expressed coding genes were as follows: defense response to
      fungus, defense response to bacterium, killing of cells of other organism and
      disruption of cells of another organism. A subsequent pathway analysis was also
      conducted, and several pathways, including the T cell receptor, MAPK, and TGF
      beta signaling pathways, were associated with the differentially expressed mRNAs.
      This study reveals the differential expression profiles of lncRNAs in the CD4+ T
      cell response to the T. pallidum infection in neurosyphilis patients. LncRNAs are
      involved in key biological processes that comprise the CD4+ T cell response to
      the T. pallidum infection.

PMID- 29167764
TI  - Barriers and Facilitators of Health Literacy among D/deaf Individuals: A Review
      Article.
AB  - Background: The implication of health literacy is the ability of individuals to
      find, understand, and use their required health information from reliable
      sources. It is an indicator of the individuals' participation in their own
      medical decision-making. Deaf individuals have limited health literacy and poor
      health status due to low literacy. Hence, this review was conducted to understand
      barriers and facilitators influencing health literacy among deaf community.
      Methods: We searched the ISI Web of Sciences, Scopus, and Medline from 1987 to
      2016. Seventy-three papers were analyzed thematically. Results: We found three
      primary themes, including inadequate health literacy, barriers, and facilitators
      to accessing health information and health care services among deaf individuals.
      Facilitators were composed of four sub-theme including legal activities
      protecting the right of deaf patients to accessing health services, training
      health professionals about effective communication with deaf patients, providing
      sign language interpreter services, and developing deaf-tailored educational
      health programs and materials. Conclusion: Closing the deaf cultural gap and
      their limited access to health information are achievable through the removal of
      the communication barriers, allowing deaf individuals with more access to health
      learning opportunities, and informing the hearing community about the
      communicative skills of deaf individuals.

PMID- 29167765
TI  - Role of Molecular Biology in Cancer Treatment: A Review Article.
AB  - Background: Cancer is a genetic disease and mainly arises due to a number of
      reasons include activation of onco-genes, malfunction of tumor suppressor genes
      or mutagenesis due to external factors. Methods: This article was written from
      the data collected from PubMed, Nature, Science Direct, Springer and Elsevier
      groups of journals. Results: Oncogenes are deregulated form of normal proto
      oncogenes required for cell division, differentiation and regulation. The
      conversion of proto-oncogene to oncogene is caused due to translocation,
      rearrangement of chromosomes or mutation in gene due to addition, deletion,
      duplication or viral infection. These oncogenes are targeted by drugs or RNAi
      system to prevent proliferation of cancerous cells. There have been developed
      different techniques of molecular biology used to diagnose and treat cancer,
      including retroviral therapy, silencing of oncogenes and mutations in tumor
      suppressor genes. Conclusion: Among all the techniques used, RNAi, zinc finger
      nucleases and CRISPR hold a brighter future towards creating a Cancer Free World.

PMID- 29167766
TI  - The Association between Short-term Exposure to Fine Particulate Matter and
      Outpatient Visit in Beijing, China.
AB  - Background: We tried to investigate the effect of PM2.5 on daily counts of
      outpatient visits in the Guang'anmen Hospital to determine if short-term PM2.5
      exposure with extremely high concentration affects cardiopulmonary function of
      Beijing residents. Methods: Outpatient visits and PM2.5 data from 01/11/2011 to
      03/31/2013 were extracted from the Guang'anmen Hospital and the American Embassy
      in Beijing, respectively. Followed by using a semi-parametric generalized
      additive model (GAM) with time dependent covariates, we analyzed the association
      between PM2.5 concentrations and daily count of outpatient visits on Day 0, 1, 2,
      3, 4 and 5 of PM2.5 exposure. Results: Overall, 284354 subjects were collected.
      There were significant associations of short-term PM2.5 exposures with outpatient
      visits for cardiopulmonary diseases (P<0.05). Specifically, a 10 MUg/m3 increase
      in PM2.5 was positively associated with a 0.74% of increase in angina visit on
      the first day and 0.50% increased visit on the second day (P<0.05). With an
      increase in PM2.5, the cough and respiratory visits significantly decreased by
      0.17% and 0.30% on the first day, respectively (P<0.05). However, there were
      significant positive associations of PM2.5 with increased cough and respiratory
      visits (increased by 0.17% and 0.10%, respectively) on the fifth day (P<0.05).
      Conclusion: Our association studies showed an instant effect of PM2.5 level on
      cardiovascular outpatient visit in the Guang'anmen Hospital in Beijing while a
      lag effect on respiratory outpatient visits.

PMID- 29167767
TI  - TP53 Gene Polymorphisms and Occupational Skin Cancer Risks for Workers of Glass
      Fiber Manufacture.
AB  - Background: Determining the role of genetic markers in individual sensitivity to
      chemical exposures raises a possibility of risk assessment of occupational
      diseases and their prevention. This paper focuses on the results of the
      identification of molecular-genetic markers associated with occupational skin
      cancer susceptibility. This study aimed to explore an association between
      polymorphisms of the TP53 tumor suppressor gene and a risk of developing
      occupational skin neoplasms. Methods: This case-control study was conducted on 71
      workers with occupational skin neoplasms, 99 healthy workers, and 100 healthy
      population-based controls in Bashkortostan Republic, Russia in 2015. Genotyping
      of TP53 polymorphisms (rs1042522, rs1625895, and rs17878362) was performed by
      restriction fragment length polymorphism analysis of genomic DNA extracted from
      peripheral blood. Odds ratios and 95% confidence intervals were calculated to
      measure the strength of the association. Results: Subjects carrying allele C of
      rs1042522 were associated with an increased risk of occupational skin neoplasms
      [P=0.027, odds ratio (OR)=1.97, 95% confidence intervals (CI) 1.08-3.63]. An
      increased risk was also associated with allele 16bp of rs17878362 (P=0.010,
      OR=3.32, 95 % CI=1.31-8.78) and allele A of rs1625895 (P=0.003, OR = 5.45, 95 %
      CI = 1.72-19.15). Conclusion: The polymorphic variants rs1042522, rs1625895 and
      rs17878362 of the TP53 gene are related to increased risks of occupational skin
      cancer. This study suggests the potential use of molecular-genetic data to assess
      increased individual risks of the development and prognosis of occupational skin
      neoplasms.

PMID- 29167768
TI  - Correlation Analysis between Obstructive Sleep Apnea Syndrome (OSAS) and Heart
      Rate Variability.
AB  - Background: Heart rate variability (HRV) represents the sympathetic nervous
      system activity induced by apnea or hypopnea events among OSAS patients. However,
      few studies have been conducted to clarify the association between HRV parameters
      and polysomnography (PSG) diagnostic indices. In our study, we postulate that the
      prevalence of cardiac arrhythmias is associated with OSAS, and HRV parameters may
      be an effective method for OSAS screening. Methods: Overall, 168 participants had
      been collected from 2011 to 2016 in the Second Affiliated Hospital of Soochow
      University. By apnea-hypopnea index (AHI), patients were separated into three
      subsets: AHI < 5 as control group, 5<=AHI<30 as mild-moderate OSAS group and
      AHI>=30as severe OSAS group. HRV and PSG parameters were collected based on
      electrocardiography and polysomnography system. Correlation analyses between
      standard deviation of R-R intervals (SDNN), SDNN index, RMSSD, PNN50, low
      frequency (LF), high frequency (HF) and LF/HF ratio and the AHI, ODI and MI were
      performed by Spearman's correlation analysis. Results: Compared with control
      group (64.5%) or mild-moderate OSAS group (67.3%), the prevalence of arrhythmias
      was considerably greater in severe OSAS group (P<0.05). Moreover, we demonstrated
      that LF/HF was greater in two OSAS groups than the normal group. Conclusion:
      Correlation analyses revealed a significant and positive relation between the
      LF/HF and AHI, ODI and MI in OSAS patients. Severe OSAS could be attributed to
      enhanced danger of incident arrhythmia. LF/HF ratio as a relevant feature may be
      an effective parameter for detecting OSAS.

PMID- 29167769
TI  - Differences in Health-related Quality of Life and Mental Health by Living
      Arrangement among Korean Elderly in the KNHANES 2010-2012.
AB  - Background: This cross-sectional study examined the association between types of
      living arrangements, quality of life, and mental health of the Korean elderly.
      Methods: We used secondary data analysis from the data of 4248 elderly people
      aged 65 yr or older that completed the Korea National Health and Nutrition
      Examination Survey (2010-2012). Data concerning participants' demographic
      characteristics, living arrangements, quality of life, and mental health were
      used. Data were analyzed using the SAS survey procedure. Results: The living
      arrangements were as follows: living alone=18.3%, living with a spouse only
      =44.5%, living with family without a spouse =13.4%, and living with family
      including a spouse=23.8%. Mobility, self-care, usual activity, pain/discomfort,
      and anxiety/depression significantly differed by living arrangement. In the final
      model corrected for covariance, for the elderly living with their families
      without a spouse compared to the elderly living with a spouse only, the odds
      ratios were the following: stress =1.40 (95% CI: 1.03-1.91), depression=1.48 (95%
      CI: 1.07-2.04), and suicidal ideation=1.48 (95% CI: 1.10-2.00). The odds ratio of
      suicidal ideation of elderly living alone compared to the elderly living with a
      spouse only was 1.32 (95% CI: 1.01-1.72). Finally, the elderly living with family
      without a spouse or living alone had an increased risk of stress, depression, and
      suicidal ideation. In addition, they had decreased health-related quality of
      life. Conclusion: Health-related quality of life and mental health differ by
      living arrangement in elderly adults. Therefore, interventions to improve quality
      of life and mental health for the elderly who are living without a spouse are
      necessary.

PMID- 29167770
TI  - A Multi-center Study on Improvement in Life Quality of Pediatric Patients with
      Asthma via Continuous Care.
AB  - Background: To analyze and summarize the effect of continuous care on the life
      quality and control of asthma of pediatric patients with asthma discharged from
      multiple hospitals. Methods: Retrospective analysis was carried out on 172
      pediatric patients with asthma aged between 6 and 11 yr old randomly selected
      from those admitted to five hospitals between January 2014 and December 2015.
      Among these 172 patients, only 86 (intervention group) received the continuous
      care between January 2015 and December 2015, while the rest (control group) did
      not receive from January 2014 and December 2014. Results: After the patients in
      the intervention group were discharged from the hospital, the ratio of practical
      forced expiratory volume in one second (FEV1) to the expected FEV1 at the 12th
      month was (90.28+/-10.35)%, and the ratio of peak expiratory flow to the expected
      value was (84.24+/-3.43)%, respectively higher than those [(82.73+/-8.86)% and
      (75.80+/-4.67)%] in the control group. Regarding pediatric asthma quality of life
      questionnaire (PAQLQ) between the intervention group and the control group, the
      difference had statistical significance (Z=-7.254, P<0.05). Childhood asthma
      control test (C-ACT) comparison between the intervention group and the control
      group indicated that the difference had statistical significance (Z=-7.918,
      P<0.05). Conclusion: Continuous care can improve the pediatric patient's
      pulmonary function and life quality, and effectively control the asthmatic
      symptoms.

PMID- 29167771
TI  - Somatic-vegetative Symptoms Evolution in Postmenopausal Women Treated with
      Phytoestrogens and Hormone Replacement Therapy.
AB  - Background: The purpose of this study was to compare the effects of the
      phytoestrogens in relieving and/or suppressing the specific somatic-vegetative
      symptoms of menopause with those of the hormone therapy, administered in small
      doses. Methods: The study was conducted in the County Clinical Emergency Hospital
      Oradea - Obstetric-Gynecological Ambulatory, and in private obstetrics-gynecology
      cabinets from Bihor County (NW Romania), from November 2011 to January 2014.
      Overall, 325 patients clinically diagnosed with specific postmenopausal
      symptomatology and not previously treated with phytoestrogens or hormone
      replacement therapy (HRT), were divided into 3 groups. Symptom assessment was
      performed with a standardized questionnaire named Menopause Rating Scale (MRS) in
      three phases: beginning of the treatment, after six months, and after one year.
      The administered doses for three different groups were as follows: 1 mg estradiol
      and 0.5 mg norethisterone acetate (NETA) p.o. daily (i.e. for the HRT group); 40
      mg of isoflavones p.o. daily - i.e. 2 capsules of 40% standardized extract
      containing 20 mg of pure isoflavones: Genistein, Daidzein, and Glycitein (i.e.
      for the group with phytoestrogens); and no trreatment for the control group.
      Results: The evolution of the somatic-vegetative symptoms was better in both
      groups treated either with phytoestrogens or HRT (P<0.001) as opposed to the
      higher percentage of patients with stationary symptoms in the control group (i.e.
      37.74% for control group, 16.13% for the group treated with phytoestrogens,
      respectively 18.95% for the group treated with HRT). Conclusion: Twelve months
      treatment study is a favorable evidence for the use of soy derived phytoestrogens
      in the treatment of somatic-vegetative symptoms at postmenopausal women.

PMID- 29167772
TI  - Guiding Effect of Serum Procalcitonin (PCT) on the Antibiotic Application to
      Patients with Sepsis.
AB  - Background: This study aimed to investigate the guiding effect of serum
      procalcitonin (PCT) on the antibiotic application to patients with sepsis.
      Methods: Ninety-eight patients with sepsis treated in Renmin Hospital of Wuhan
      University, China from 2015-2017 were enrolled. They were divided into two equal
      groups of control group and the observation group. Patients in the observation
      group received the antibiotic therapy guided by PCT while patients in the control
      group received the regular antibiotic therapy. The conventional indexes,
      prognosis and clinical effects of the two groups were compared. Results: There
      were no statistical significance in the differences of the Acute Physiology and
      Chronic Health Evaluation II (APACHE-II) scores C-reactive protein (CRP) and
      white blood cell count (WBC) levels between the two groups. The duration of the
      antibiotic application to patients in the observation group was (7.74+/-0.61) d
      which was (10.22+/-0.78) d shorter than that to patients in the control group.
      The difference was statistically significant (P<0.05). The Intensive Care Unit
      (ICU) stay time and the hospital stays of patients in the observation group were
      shorter than those of patients in the control group. The difference had
      statistical significance (P<0.05). The difference in 30-day-recurrence rate and
      30 day-mortality of the patients in the two groups had no statistical
      significance. There was statistically significant difference in the comparison of
      the clinical effects between the two groups. Conclusion: Guiding effects of the
      serum PCT on the application of antibiotics to patients with sepsis shorten the
      usage time of the antibiotics, ICU stay time and hospital stays.

PMID- 29167773
TI  - Prevalence of Aflatoxin Contamination in Herbs and Spices in Different Regions of
      Iran.
AB  - Background: Mycotoxins are natural toxins, produced by several fungal species and
      are associated with morbidity or even mortality in animals, plants, and humans.
      In this study, 120 samples of herbs and spices in both bulk and packaged forms
      were prepared in order to measure aflatoxin level in different regions of Iran.
      Methods: The aflatoxin was extracted during Mar to May 2015, using 80% methanol
      and then purified via immunoaffinity column. Measurements were performed, using
      high-performance liquid chromatography, equipped with a fluorescence detection
      system at excitation and emission wavelengths of 365 and 435 nm, respectively.
      Results: The highest prevalence of aflatoxin contamination in food products was
      attributed to aflatoxin B1 (30.8%). In addition, the highest prevalence of
      aflatoxin contamination was reported in red pepper (100%). Examination of
      effective factors indicated the substantial impact of moisture on aflatoxin level
      (P=0.046). Conclusion: Even at low levels of aflatoxin, contamination could be a
      serious threat, given the prevalent use of spices (either raw or not) as
      ingredients in food preparation. Therefore, regular monitoring of spices,
      especially chili pepper, is highly recommended.

PMID- 29167774
TI  - Anthropometric Indices as Predictors of Coronary Heart Disease Risk: Joint
      Modeling of Longitudinal Measurements and Time to Event.
AB  - Background: The prevalence of overweight and obesity have increased dramatically
      worldwide and together they constitute a major risk factor for coronary heart
      disease (CHD). The aim of this study was to assess the repeated measurements of
      body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and
      waist to height ratio (WHtR) in predicting CHD incidence. Methods: This
      longitudinal study was conducted within the framework of the Tehran Lipid and
      Glucose Study between 1999-2011, on 1959 women and 1371 men participants' ages
      >=30 yr, without a history of CVD. A joint modeling approach was utilized for
      data analysis using R software. The resulting joint model allowed measuring alpha
      (quantifies the association between anthropometric indices up to time t and the
      hazard for CHD event at the same time point). Results: About 9% of the
      participants (7.1% of the women and 11.7% of the men) experienced CHD event
      during follow-up. The results indicated a significant linear increasing trend in
      BMI, WC, WHR, and WHtR over time (P<0.001). The increased risk of CHD event in
      females increases with the values of BMI (alpha= 0.004, P=0.023), WC (alpha=
      0.018, P=0.009), WHR (alpha= 0.067, P=0.014) and WHtR (alpha= 0.106, P=0.002).
      Furthermore, in males the risk of CHD risk increases by the values of BMI (alpha=
      0.005, P=0.032), WC (alpha= 0.019, P=0.008), WHR (alpha= 0.043, P=0.015) and WHtR
      (alpha= 0.096, P=0.002). Conclusion: By jointly modeling longitudinal data with
      time-to-event outcomes, our study revealed that WHtR is superior to other indices
      in predicting CHD incidence.

PMID- 29167775
TI  - A Model for the Development of Hospital Beds Using Fuzzy Analytical Hierarchy
      Process (Fuzzy AHP).
AB  - Background: This study aimed to identify and prioritize factors affecting the
      development of military hospital beds and provide a model using fuzzy analytical
      hierarchy process (Fuzzy AHP). Methods: This applied study was conducted in 2016
      in Iran using a mixed method. The sample included experts in the field of
      military health care system. The MAXQDA 10.0 and Expert Choice 10.0 software were
      used for analyzing the collected data. Results: Geographic situation, demographic
      status, economic status, health status, health care centers and organizations,
      financial and human resources, laws and regulations and by-laws, and the military
      nature of service recipients had effects on the development of military hospital
      beds. The military nature of service recipients (S=0.249) and economic status
      (S=0.040) received the highest and lowest priorities, respectively. Conclusion:
      Providing direct health care services to the military forces in order to maintain
      their dignity, and according to its effects in the crisis, as well as the
      necessity for maintaining the security of the armed forces, and the hospital beds
      per capita based on the existing laws, regulations and bylaws are of utmost
      importance.

PMID- 29167776
TI  - Prognosis and Early Diagnosis of Ductal and Lobular Type in Breast Cancer
      Patient.
AB  - Background: Breast cancer is one of the most common cancers with a high mortality
      rate among women. Prognosis and early diagnosis of breast cancer among women
      society reduce considerable rate of their mortality. Nowadays, due to this
      illness, try to be setting up intelligent systems, which can predict and early
      diagnose this cancer, and reduce mortality of women society. Methods: Overall,
      208 samples were collected from 2014 to 2015 from two oncologist offices and
      Javadalaemeh Clinic in Kerman, southeastern Iran. Data source was medical records
      of patients, then 64 data mining models in MATLAB and WEKA software were used,
      eventually these measured precision and accuracy of data mining models. Results:
      Among 64 data mining models, Bayes-Net model had 95.67% of accuracy and 95.70% of
      precision; therefore, was introduced as the best model for prognosis and
      diagnosis of breast cancer. Conclusion: Intelligent and reliable data mining
      models are proposed. Hence, these models are recommended as a useful tool for
      breast cancer prediction as well as medical decision-making.

PMID- 29167777
TI  - Age and Spatial Peculiarities of Non-neoplastic Diseases of the Skin and
      Subcutaneous Tissue in Kazakhstan, 2003-2015.
AB  - Background: Arrangement of effective management aimed at improving dermatological
      services and consistent care of patients with skin diseases depends on
      understanding the epidemiological situation. Methods: This retrospective study
      presents an epidemiological assessment of non-neoplastic skin and subcutaneous
      tissue diseases in Kazakhstan registered in 2003-2015. Results: The yearly
      incidence rate of the diseases among the whole population was in average
      3,341.8+/-121.1 per 100000 population. This represents 4835.0+/-156.1 for
      children, 5503.2+/-141.8 for adolescents and 2646.6+/-106.7 for adults per 100000
      inhabitants. Space and time incidence rate was evaluated according to the
      administrative division. The overall trend decreased to 3.5% in children to 2.8%
      in adolescents to 1.9%, and in adults to 3.9%. Considerable variation in rates
      was seen across the country, with highest rates in East Kazakhstan, Mangystau and
      Aktobe regions, the lowest - in Atyrau and South-Kazakhstan regions. Conclusion:
      Non-neoplastic diseases of skin and subcutaneous tissue continue to be an urgent
      public health problem, especially among children in many regions of Kazakhstan.

PMID- 29167778
TI  - Functional Recovery of Patient Whit Ischemic Stroke: Case Report.
AB  - Vascular lesions of the central nervous system are one of the most important and
      topical problems in modern neuro-pathology. Bulgaria is among the first in
      morbidity and mortality from cerebrovascular diseases. Because of the significant
      medical and social importance of this pathology resulting in severe disabling of
      most survivors, we aimed to explore the effectiveness of kinesitherapeutic
      methodology applied in the recovery of a patient with ischemic stroke. We present
      a case of a 69-old patient admitted in the Neurological Ward of "St. George
      Hospital in Plovdiv in 2015, Bulgaria with right hemiparesis due to ischemic
      stroke in the basin of the left middle cerebral artery. The applied Kinesi
      therapeutic methodology included various techniques like Kabat's Bobath's methods
      as well as training in equilibrium and walking. The patient obtained satisfactory
      results in terms of movement of the body and preserving the equilibrium,
      improvement of voluntary movement of the upper and lower right limb achieved via
      the help of some compensatory mechanisms. Despite the applied Kinesitherapy, the
      patient failed to gain independence in daily activities. We ascribe this
      satisfactory recovery only to the short period of application of
      kinesitherapeutic methodology. For a better recovery of patients with
      cerebrovascular disease, a continuous multidisciplinary approach is needed.

PMID- 29167779
TI  - Bibliometric Analysis on the Risks of Oral Cancer for People Living with
      HIV/AIDS.

PMID- 29167780
TI  - Comparison of Health Level and Physical Activity between Korean and Other
      Countries Female College Students.

PMID- 29167781
TI  - Gaps in Iranian School-leavers' Current Knowledge of Nutrition and Food Systems.

PMID- 29167782
TI  - Oral Health Status of Children with Autistic Spectrum Disorder Compared with Non
      authentic Peers.

PMID- 29167783
TI  - Semiparametric Accelerated Failure Time Model as a New Approach for Health
      Science Studies.

PMID- 29167784
TI  - Main Determinants of Ossification in Humerus Bone and Coracoid Process among
      Iranian Neonates.

PMID- 29167785
TI  - Molecular Diagnostics with Laboratory Finding in Patients with Myeloproliferative
      Neoplasms.

PMID- 29167786
TI  - Reply to Urbanization Theory for Growing Trend of Multiple Sclerosis Letter.

PMID- 29167787
TI  - Medicine Availability and Prescribing Policy for Non-Communicable Diseases in the
      Western Balkan Countries.
AB  - Background: During the transition processes, the Western Balkan countries were
      affected by conflicts and transition-related changes. Life expectancy in these
      countries is lower, while the mortality from non-communicable diseases (NCDs) is
      higher in comparison with western and northern parts of Europe. The primary aim
      of this study was to analyze the treatment possibilities for the most common NCDs
      in the Western Balkan countries. The secondary aim was to understand and compare
      the policies regarding prescribing-related competencies of family physicians.
      Methods: In June and July 2017, a document analysis was performed of national
      positive medicines lists, strategic documents, and clinical guidelines for the
      treatment of the most frequent NCDs; arterial hypertension, diabetes,
      hyperlipidemia, asthma, and chronic obstructive pulmonary disease (COPD). All
      text phrases that referred to medicines prescribing were extracted and sorted
      into following domains: medicine availability, prescribing policy, and medication
      prescribing-related competencies. Results: Possibilities for treatment of
      arterial hypertension, diabetes, hyperlipidemia, asthma, and COPD vary across the
      Western Balkan countries. This variance is reflected in the number of registered
      medicines, number of parallels, and number of different combinations, as well as
      restrictions placed on family physicians in prescribing insulin, inhaled
      corticosteroids, statins and angiotensin II receptor blockers (ARBs), without
      consultant's recommendation. Conclusion: Western Balkan countries are capable of
      providing essential medicines for the treatment of NCDs, with full or partial
      reimbursement. There are some exceptions, related to statins, newer generation of
      oral antidiabetic agents and some of the antihypertensive combinations.
      Prescribing-related competences of family physicians are limited. However, this
      practice is not compliant to the practices of family medicine, its principles and
      primary care structures, and may potentially result in increased health-care
      financial ramifications to both the system and patients due to frequent referrals
      to the specialists.

PMID- 29167788
TI  - Examining Capacity and Functioning of Bicycle Coalitions: A Descriptive Study.
AB  - Background: Bicycle coalitions represent a strong partner in creating bike
      friendly communities through advocacy for physical infrastructure, encouragement
      for biking, or education about safety. Despite their versatility, little is known
      about their functioning. Therefore, the purpose of this study was to examine
      capacity, strengths, and weaknesses of these organizations. Methods: Bicycle
      coalitions/advocacy groups from English-speaking countries were recruited to take
      part in an online survey via email invitation. The survey addressed basic
      information about the coalition (community demographics, location), leadership,
      communication strategies, coalition priorities, barriers to
      programming/activities, and partners. Results: Coalitions (n = 56) from four
      countries completed the survey. Most coalitions operated as a non-profit (n = 44,
      95.7%), 45% (n = 21) have paid staff as leaders, while 37% (n = 17) have
      volunteers as leaders. The following skills were represented in coalitions'
      leadership: fundraising (n = 31, 53.4%), event planning (n = 31, 53.4%), urban
      planning (n = 26, 44%), and policy/legislation expertise (n = 26, 44.8%).
      Education (n = 26, 63.4%) and encouragement (n = 25, 61.6%) were viewed as top
      priorities and the safety of bicyclists (n = 21, 46.7%) and advocacy for
      infrastructure and policy (n = 22, 48.9%) is the focus of most activities. A lack
      of financial resources (n = 36, 81.8%) and capable personnel (n = 25, 56.8%) were
      significant barriers to offering programming in the community and that the
      availability of grants to address issues (n = 38, 86.4%) would be the top
      motivator for improvements. Conclusion: Bike coalitions represent a critical
      partner in creating activity-friendly environments and understanding their
      capacity allows for creating skill/capacity building intervention programs,
      development of effective toolkits and fostering strong collaborations to address
      physical inactivity.

PMID- 29167789
TI  - Radical SAM Enzymes in the Biosynthesis of Ribosomally Synthesized and Post
      translationally Modified Peptides (RiPPs).
AB  - Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a
      large and diverse family of natural products. They possess interesting biological
      properties such as antibiotic or anticancer activities, making them attractive
      for therapeutic applications. In contrast to polyketides and non-ribosomal
      peptides, RiPPs derive from ribosomal peptides and are post-translationally
      modified by diverse enzyme families. Among them, the emerging superfamily of
      radical SAM enzymes has been shown to play a major role. These enzymes catalyze
      the formation of a wide range of post-translational modifications some of them
      having no counterparts in living systems or synthetic chemistry. The
      investigation of radical SAM enzymes has not only illuminated unprecedented
      strategies used by living systems to tailor peptides into complex natural
      products but has also allowed to uncover novel RiPP families. In this review, we
      summarize the current knowledge on radical SAM enzymes catalyzing RiPP post
      translational modifications and discuss their mechanisms and growing importance
      notably in the context of the human microbiota.

PMID- 29167790
TI  - Engineered Nickel Oxide Nanoparticle Causes Substantial Physicochemical
      Perturbation in Plants.
AB  - Concentration of engineered nickel oxide nanoparticle (NiO-NP) in nature is on
      the rise, owing to large scale industrial uses, which have accreted the scope of
      its exposure to plants, the primary producers of the ecosystem. Though an
      essential micronutrient for the animal system, supported by numerous studies
      confirming its toxicity at higher dosages, nickel oxide is graded as a human
      carcinogen by WHO. A few studies do depict toxicity and bioaccumulation of nickel
      in plants; however, interaction of NiO-NP with plants is not well-elucidated. It
      is known that exposure to NiO-NP can incite stress response, leading to
      cytotoxicity and growth retardation in some plants, but a defined work on the
      intricate physicochemical cellular responses and genotoxic challenges is wanting.
      The present study was planned to explore cytotoxicity of NiO-NP in the model
      plant, Allium cepa L., its internalization in the tissue and concomitant furore
      created in the antioxidant enzyme system of the plant. The prospect of the NiO-NP
      causing genotoxicity was also investigated. Detailed assessments biochemical
      profiles and genotoxicity potential of NiO-NP on A. cepa L. was performed and
      extended to four of its closest economically important relatives, Allium sativum
      L., Allium schoenoprasum L., Allium porrum L., and Allium fistulosum L. Growing
      root tips were treated with seven different concentrations of NiO-NP suspension
      (10-500 mg L-1), with deionised distilled water as negative control and 0.4 mM
      EMS solution as positive control. Study of genotoxic endpoints, like, mitotic
      indices (MI), chromosomal aberrations (CAs), and chromosome breaks confirmed NiO
      NP induced genotoxicity in plants, even at a very low dose (10 mg L-1). That NiO
      NP also perturbs biochemical homeostasis, disrupting normal physiology of the
      cell, was confirmed through changes in state of lipid peroxidation malonaldehyde
      (MDA), as well as, in oxidation marker enzymes, like catalase (CAT), super oxide
      dismutase (SOD), and guiacol peroxidase (POD) activities. It was evident that
      increase in NiO-NP concentration led to decrease in MIs in all the study
      materials, concomitant with a spike of stress-alleviating, antioxidant enzymes
      CAT, POD, SOD, and significant increase in MDA formation. Hence, it can be
      confirmed that NiO-NP should be treated as an environmental hazard.

PMID- 29167791
TI  - Is Delirium the Cognitive Harbinger of Frailty in Older Adults? A Review about
      the Existing Evidence.
AB  - Frailty is a clinical syndrome defined by the age-related depletion of the
      individual's homeostatic reserves, determining an increased susceptibility to
      stressors and disproportionate exposure to negative health changes. The
      physiological systems that are involved in the determination of frailty are
      mutually interrelated, so that when decline starts in a given system,
      implications may also regard the other systems. Indeed, it has been shown that
      the number of abnormal systems is more predictive of frailty than those of the
      abnormalities in any particular system. Delirium is a transient neurocognitive
      disorder, characterized by an acute onset and fluctuating course, inattention,
      cognitive dysfunction, and behavioral abnormalities, that complicates one out of
      five hospital admissions. Delirium is independently associated with the same
      negative outcomes of frailty and, like frailty, its pathogenesis is usually
      multifactorial, depending on complex inter-relationships between predisposing and
      precipitating factors. By definition, a somatic cause should be identified, or at
      least suspected, to diagnose delirium. Delirium and frailty potentially share
      multiple pathophysiologic mechanisms and pathways, meaning that they could be
      thought of as the two sides to the same coin. This review aims at summarizing the
      existing evidence, referring both to human and animal models, to postulate that
      delirium may represent the cognitive harbinger of a state of frailty in older
      persons experiencing an acute clinical event.

PMID- 29167792
TI  - Translation of the 5D Itching Scale from English to Malay, and Its Validation
      among Patients with Chronic Kidney Disease in Malaysia.
AB  - Introduction: Several tools have been developed to assess the severity of
      pruritus. In Malaysia, no tool has been validated to assess pruritus in patients
      with chronic kidney disease (CKD). Therefore, the aim of our study was to
      validate the Malay 5D itching scale (M5D-IS) among patients with CKD in Malaysia.
      Method: The English version of the 5D-IS was translated into Malay according to
      International Guidelines. Face and content validity was determined by an expert
      panel and pilot tested in patients with end-stage renal disease (ESRD). The M5D
      IS was then validated in a tertiary hospital in Malaysia from May to June 2016.
      We recruited patients with (i.e., patients with ESRD) and without pruritus (i.e.,
      patients with stage 1-3 CKD) (to determine if the M5D-IS could discriminate
      between the two groups), and administered the M5D-IS at baseline and 2 weeks
      later. Exploratory factor analysis was used to examine the construct validity.
      Internal consistency was assessed using Cronbach's alpha and intraclass
      correlation coefficient was calculated to assess the reliability of the
      instrument. Results: A total of 70 participants were recruited (response rate =
      100%). The majority were males (51.4%) and Malay (67.1%). Exploratory factor
      analysis revealed that the 5D-IS had 2-factor loadings: "daily routine activity"
      and "pattern of itching," which explained 77.7% of the variance. The overall
      score of the M5D-IS, as well as for each domain, was significantly worse in
      participants with pruritus (9.83 +/- 0.35), compared to those without pruritus
      (5.51 +/- 0.93, p < 0.001). The overall Cronbach's alpha for the M5D-IS was
      (0.861), indicating adequate internal consistency. At test-retest, the intraclass
      correlation coefficient was significantly correlated. Conclusion: The M5D-IS was
      found to be a valid and reliable instrument to assess pruritus among patients
      with CKD in Malaysia.

PMID- 29167793
TI  - Health and Lifestyles Factors Associated With Osteoarthritis among Older Adults
      in Portugal.
AB  - Objective: This study aimed to identify independent associations of
      sociodemographic, functionality, physical activity, physical and mental health,
      and osteoarthritis (OA), among older adults. Methods: A sample of 1,645 older
      adults (50+ years) observed by rheumatologists, from EpiReumaPt, a population
      based study was analyzed. A structured interview included sociodemographic data,
      chronic non-communicable disease, and physical activity. Functional ability was
      assessed by the Health Assessment Questionnaire Disability Index; depression and
      anxiety were assessed by Hospital Anxiety and Depression Scale. OA (knee OA
      and/or hip OA and/or hand OA) was defined after medical evaluation by
      rheumatologists according to expert opinion combined with the fulfillment of the
      American College of Rheumatology classification criteria. Results: 1,059
      participants (64.9%) met the OA classification criteria. Statistically
      significant differences were found between persons with and without OA in all
      sociodemographic variables, non-communicable diseases, functional status,
      physical activity, depression, and anxiety. In the unadjusted logistic regression
      models, all variables were associated with OA. The final adjusted model explained
      32% of the variance. Those who are female with higher age, have more than five
      comorbidities, and lower levels of function and physical activity were more
      likely to meet the criteria for a diagnosis of OA. Discussion: We have analyzed
      data from a population-based study and found that a diagnosis of OA was
      independently associated with age, female gender, higher number of comorbidities,
      physical disability, and low levels of physical activity. These results reinforce
      the usefulness of the development of a multidimensional assessment to design and
      test effective interventions for this population.

PMID- 29167794
TI  - Case Report of Urethritis in a Male Patient Infected with Two Different Isolates
      of Multiple Drug-Resistant Neisseria gonorrhoeae.
AB  - We report a brief description of a case suffering from bacterial urethritis,
      conjunctivitis, and arthritis, caused by two different isolates of multiple drug
      resistant Neisseria gonorrhoeae. Initial diagnosis was dependent on the patient
      history, clinical findings, symptoms, and the bacteriological data. Polymerase
      chain reaction confirmed the identification of the pathogens. Random amplified
      polymorphic DNA revealed two different patterns. Susceptibility testing was
      performed using Kirby-Bauer disk diffusion method and the minimum inhibitory
      concentration was also determined. It revealed multiple drug resistance
      associated with beta-lactamase production. Only gentamicin, rifampicin, and
      azithromycin were active against the test pathogens. A dual therapy was initiated
      using gentamicin as well as azithromycin to treat the possible co-infection with
      Chlamydia trachomatis. Complete recovery of the patient achieved with resolved
      symptoms a week later.

PMID- 29167796
TI  - Tinnitus after Simultaneous and Sequential Bilateral Cochlear Implantation.
AB  - Importance: There is an ongoing global discussion on whether or not bilateral
      cochlear implantation should be standard care for bilateral deafness. Contrary to
      unilateral cochlear implantation, however, little is known about the effect of
      bilateral cochlear implantation on tinnitus. Objective: To investigate tinnitus
      outcomes 1 year after bilateral cochlear implantation. Secondarily, to compare
      tinnitus outcomes between simultaneous and sequential bilateral cochlear
      implantation and to investigate long-term follow-up (3 years). Study design: This
      study is a secondary analysis as part of a multicenter randomized controlled
      trial. Methods: Thirty-eight postlingually deafened adults were included in the
      original trial, in which the presence of tinnitus was not an inclusion criterion.
      All participants received cochlear implants (CIs) because of profound hearing
      loss. Nineteen participants received bilateral CIs simultaneously and 19
      participants received bilateral CIs sequentially with an inter-implant interval
      of 2 years. The prevalence and severity of tinnitus before and after simultaneous
      and sequential bilateral cochlear implantation were measured preoperatively and
      each year after implantation with the Tinnitus Handicap Inventory (THI) and
      Tinnitus Questionnaire (TQ). Results: The prevalence of preoperative tinnitus was
      42% (16/38). One year after bilateral implantation, there was a median difference
      of -8 (inter-quartile range (IQR): -28 to 4) in THI score and -9 (IQR: -17 to -9)
      in TQ score in the participants with preoperative tinnitus. Induction of tinnitus
      occurred in five participants, all in the simultaneous group, in the year after
      bilateral implantation. Although the preoperative and also the postoperative
      median THI and TQ scores were higher in the simultaneous group, the median
      difference scores were equal in both groups. In the simultaneous group, tinnitus
      scores fluctuated in the 3 years after implantation. In the sequential group,
      four patients had an additional benefit of the second CI: a total suppression of
      tinnitus compared with their unilateral situation. Conclusion: While bilateral
      cochlear implantation can have a positive effect on preoperative tinnitus
      complaints, the induction of (temporary or permanent) tinnitus was also reported.
      Clinical Trial Registration: Dutch Trial Register NTR1722.

PMID- 29167797
TI  - A Subset of Dogs with Presumptive Idiopathic Epilepsy Show Hippocampal Asymmetry:
      A Volumetric Comparison with Non-Epileptic Dogs Using MRI.
AB  - MRI-acquired volumetric measurements from 100 dogs with presumptive idiopathic
      epilepsy (IE) and 41 non-epileptic (non-IE) dogs were used to determine if
      hippocampal asymmetry exists in the IE as compared to the non-IE dogs. MRI
      databases from three institutions were searched for dogs that underwent MRI of
      the brain and were determined to have IE and those that were considered non-IE
      dogs. Volumes of the right and left hippocampi were measured using Mimics(r)
      software. Median hippocampal volumes of IE and non-IE dogs were 0.47 and 0.53
      cm3, respectively. There was no significant difference in overall hippocampal
      volume between IE and non-IE dogs; however, IE dogs had greater hippocampal
      asymmetry than non-IE dogs (P < 0.012). A threshold value of 1.16 from the
      hippocampal ratio had an 85% specificity for identifying IE-associated asymmetry.
      Thirty five percent of IE dogs had a hippocampal ratio >1.16. Asymmetry was not
      associated with any particular hemisphere (P = 0.67). Our study indicates that
      hippocampal asymmetry occurs in a subset of dogs with presumptive
      idiopathic/genetic epilepsy, suggesting a structural etiology to some cases of
      IE.

PMID- 29167798
TI  - Uncovering the hidden: complexity and strategies for diagnosing latent
      tuberculosis.
AB  - Tuberculosis produces two clinical manifestations: active and latent (non
      apparent) disease. The latter is estimated to affect one-third of the world
      population and constitutes a source of continued transmission should the disease
      emerge from its hidden state (reactivation). Methods to diagnose latent TB have
      been evolving and aim to detect the disease in people who are truly infected with
      M. tuberculosis, versus those where other mycobacteria, or even other pathologies
      not related to TB, are present. The current use of proteomic and transcriptomic
      approaches may lead to improved detection methods in the coming years.

PMID- 29167795
TI  - Managing Rheumatoid Arthritis with Dietary Interventions.
AB  - Self-help by means of dietary interventions can help in management of various
      disorders including rheumatoid arthritis (RA), a debilitating autoimmune disease.
      Dietary interventions necessitate a widespread appeal for both patients as well
      as clinicians due to factors including affordability, accessibility, and presence
      of scientific evidences that demonstrate substantial benefits in reducing disease
      symptoms such as pain, joint stiffness, swelling, tenderness and associated
      disability with disease progression. However, there is still an uncertainty among
      the community about the therapeutic benefits of dietary manipulations for RA. In
      the present review, we provide an account of different diets and their possible
      molecular mechanism of actions inducing observed therapeutic benefits for
      remission and management of RA. We further indicate food that can be a potential
      aggravating factor for the disease or may help in symptomatic relief. We
      thereafter summarize and thereby discuss various diets and food which help in
      reducing levels of inflammatory cytokines in RA patients that may play an
      effective role in management of RA following proper patient awareness. We thus
      would like to promote diet management as a tool that can both supplement and
      complement present treatment strategies for a better patient health and recovery.

PMID- 29167799
TI  - The integrated stress response in budding yeast lifespan extension.
AB  - Aging is a complex, multi-factorial biological process shared by all living
      organisms. It is manifested by a gradual accumulation of molecular alterations
      that lead to the decline of normal physiological functions in a time-dependent
      fashion. The ultimate goal of aging research is to develop therapeutic means to
      extend human lifespan, while reducing susceptibility to many age-related diseases
      including cancer, as well as metabolic, cardiovascular and neurodegenerative
      disorders. However, this first requires elucidation of the causes of aging, which
      has been greatly facilitated by the use of model organisms. In particular, the
      budding yeast Saccharomyces cerevisiae has been invaluable in the identification
      of conserved molecular and cellular determinants of aging and for the development
      of approaches to manipulate these aging determinants to extend lifespan.
      Strikingly, where examined, virtually all means to experimentally extend lifespan
      result in the induction of cellular stress responses. This review describes
      growing evidence in yeast that activation of the integrated stress response
      contributes significantly to lifespan extension. These findings demonstrate that
      yeast remains a powerful model system for elucidating conserved mechanisms to
      achieve lifespan extension that are likely to drive therapeutic approaches to
      extend human lifespan and healthspan.

PMID- 29167800
TI  - Cross-species complementation of bacterial- and eukaryotic-type cardiolipin
      synthases.
AB  - The glycerophospholipid cardiolipin is a unique constituent of bacterial and
      mitochondrial membranes. It is involved in forming and stabilizing high molecular
      mass membrane protein complexes and in maintaining membrane architecture. Absence
      of cardiolipin leads to reduced efficiency of the electron transport chain,
      decreased membrane potential, and, ultimately, impaired respiratory metabolism.
      For the protozoan parasite Trypanosoma brucei cardiolipin synthesis is essential
      for survival, indicating that the enzymes involved in cardiolipin production
      represent potential drug targets. T. brucei cardiolipin synthase (TbCLS) is
      unique as it belongs to the family of phospholipases D (PLD), harboring a
      prokaryotic-type cardiolipin synthase (CLS) active site domain. In contrast, most
      other eukaryotic CLS, including the yeast ortholog ScCrd1, are members of the CDP
      alcohol phosphatidyltransferase family. To study if these mechanistically
      distinct CLS enzymes are able to catalyze cardiolipin production in a cell that
      normally expresses a different type of CLS, we expressed TbCLS and ScCrd1 in CLS
      deficient yeast and trypanosome strains, respectively. Our results show that
      TbCLS complemented cardiolipin production in CRD1 knockout yeast and partly
      restored wild-type colony forming capability under stress conditions. Remarkably,
      CL remodeling appeared to be impaired in the transgenic construct, suggesting
      that CL production and remodeling are tightly coupled processes that may require
      a clustering of the involved proteins into specific CL-synthesizing domains. In
      contrast, no complementation was observed by heterologous expression of ScCrd1 in
      conditional TbCLS knockout trypanosomes, despite proper mitochondrial targeting
      of the protein.

PMID- 29167801
TI  - Breaking the bad: Bacillus blocks fungal virulence factors.
AB  - Fungal pathogens rely on the production of specific virulence factors during
      infection. Inhibiting such factors generally results in reduced fungal
      pathogenicity. Most studies in the past have focused on understanding the
      molecular mechanisms of fungal virulence factor expression during mono-culture,
      or during interaction with the host. However, a potentially important, second
      type of interaction has been less well studied thus far - the interplay of fungal
      pathogens of humans with other microbes found in their natural habitat.
      Specifically, whether environmental bacteria may impact fungal virulence factor
      production is largely unknown. In our recent work, we have identified the soil
      bacterium, Bacillus safensis, as a potent inhibitor of virulence factor
      production by two major fungal pathogens of humans, Cryptococcus neoformans, and
      Candida albicans. We determined that the anti-virulence factor mechanism is, at
      least in part, based on production of bacterial chitinases that target and
      destabilize the fungal cell surface. These findings describe a cross-kingdom
      interaction between an environmental bacterium and pathogenic fungi, and
      highlight the fungal cell wall as an attractive antifungal drug target.

PMID- 29167802
TI  - Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase.
AB  - Viruses manipulate cellular processes to create an environment favorable to
      replication. For most viruses, this includes subverting the expression of
      interferon (IFN), a signaling molecule that can stimulate production of a vast
      array of antiviral gene products. Rotavirus, a segmented double-stranded RNA
      virus that causes acute gastroenteritis in infants and young children, inhibits
      IFN expression through its nonstructural protein NSP1. This viral protein stifles
      IFN expression by inducing the degradation of host factors that are necessary for
      upregulating the activity of IFN genes. In the case of nearly all human and
      porcine rotavirus strains, NSP1 induces the ubiquitination-dependent proteasomal
      degradation of beta-transducin repeat containing protein (beta-TrCP), a host
      factor that plays an essential role in activating the IFN-transcription factor,
      NF-kappaB. Key to the process is the presence of a decoy sequence (degron) at the
      C-terminus of NSP1 that causes beta-TrCP to mistakenly bind NSP1 instead of its
      natural target, inhibitor-of-kappaB (IkappaB). In a recent report published by
      Davis et al [2017; mBio 8(4): e01213-17], we describe molecular requirements that
      govern NSP1 recognition of beta-TrCP, including an essential degron
      phosphorylation event, and the step-wise incorporation of NSP1 into hijacked
      cullin-RING E3 ligases (CRLs) that ubiquitinate and tag beta-TrCP for
      degradation. Notably, although beta-TrCP is chiefly recognized for its role as a
      master regulator of NF-kappaB signaling and IFN expression, beta-TrCP also
      controls the stability of checkpoint proteins implicated in numerous other
      cellular pathways with antiviral activities, including autophagy and apoptosis.
      Thus, the impact of NSP1 on creating an intracellular environment favorable to
      virus replication may extend well beyond the IFN signaling pathway.

PMID- 29167803
TI  - There and back again: amitosis to repopulate a stem cell pool.

PMID- 29167804
TI  - Extracellular vesicle-mediated transport of non-coding RNAs between stem cells
      and cancer cells: implications in tumor progression and therapeutic resistance.
AB  - Recent years have witnessed intensive progress in studying extracellular vesicles
      (EVs), both for understanding their basic biology and contribution to variety of
      diseases, biomarker discovery, and their potential as gene delivery vectors and
      source of innovative therapies. As such, stem cell-derived EVs have contributed
      significant knowledge which led to the development of cell-free therapies in
      regenerative medicine. Although, the role of stem cell-derived EVs in maintaining
      stemness, differentiation and repairing tissue injuries is relatively well
      understood; however, knowledge about the contribution of stem cell-derived EVs in
      cancer progression is just emerging. The aim of this review is, therefore, to
      discuss the recent developments in stem cell-derived EVs and tumor progression,
      placing a particular focus on non-coding RNA (ncRNA) mediated cancer progression
      and resistance against therapies. This includes the failure of normal
      hematopoiesis and the progression of myeloid neoplasms, enhanced capacity of
      cancer cells to proliferate and metastasize, and the conversion of normal cells
      into cancer cells, activation of angiogenic pathways and dormancy in cancer
      cells. These processes are shared by mesenchymal stem cells (MSCs), cancer stem
      like-cells and cancer cells in an intricate intratumoral network in order to
      create self-strengthening tumor niche. In this context, EV-ncRNAs serve as
      mediators to relay bystander effects of secreting cancer stem cells (CSCs) into
      recipient cells for priming a tumor permissive environment and relaying
      therapeutic resistance. Collectively, this knowledge will improve our
      understandings and approaches in finding new therapeutic targets in the context
      of CSCs, which could be benefited through engineering EVs for innovative
      therapies.

PMID- 29167805
TI  - Clinical potential of mesenchymal stem/stromal cell-derived extracellular
      vesicles.
AB  - Within the last two decades mesenchymal stem/stromal cells (MSCs) emerged after
      hematopoietic stem cells as the second most investigated and applied somatic stem
      cell entity so far. MSCs mediate immunosuppressive as well as pro-regenerative
      activities. Against the initial assumption, MSCs may not primarily exert their
      therapeutic functions in a cellular but rather in a paracrine manner. Here,
      extracellular vesicles (EVs), such as exosomes and microvesicles, have been
      identified as major mediators of these paracrine effects. Meanwhile, MSC-EVs have
      been applied to an increasing amount of different animal models and were tested
      in a patient suffering from steroid-refractory acute graft-versus-host disease
      (acute GvHD) as well as in a patient cohort with chronic kidney disease. So far,
      the MSC-EV administration appears to be safe in humans and all tested animal
      models. Improvements were reported in all settings. Thus, MSC-EVs appear as
      promising novel therapeutic agents which might help to improve disease associated
      symptoms in millions of patients. Here, we review some of the milestones in the
      field, briefly discuss challenges and highlight clinical aspects of acute GvHD
      and its treatment with MSCs and MSC-EVs.

PMID- 29167806
TI  - Aplastic anemia is related to alterations in T cell receptor signaling.
AB  - Aplastic anemia (AA) is a disease characterized by bone marrow hematopoietic
      dysfunction and peripheral blood pancytopenia, which is thought to be mediated by
      an abnormal T cell-induced immune response. T cell receptor (TCR) signaling is
      pivotal for T cell development and function. An aberrant TCR signaling leads to
      an unbalanced immune system that can result in a range of immune-related
      disorders, including autoimmune diseases, chronic infections, and tumors. In this
      article, we briefly review the T cell immune pathophysiology of AA, the
      physiology of normal TCR signaling and its regulatory factors, and clinical and
      laboratory findings of TCR signaling molecules and their regulatory factors in
      AA.

PMID- 29167807
TI  - Nicotinamide: a novel treatment for age-related macular degeneration?

PMID- 29167808
TI  - Small incision lenticule extraction (SMILE) in the correction of myopic
      astigmatism: outcomes and limitations - an update.
AB  - Small Incision Lenticule Extraction (SMILE) is a flap-free intrastromal technique
      for the correction of myopia and myopic astigmatism. To date, this technique
      lacks automated centration and cyclotorsion control, so several concerns have
      been raised regarding its capability to correct moderate or high levels of
      astigmatism. The objective of this paper is to review the reported SMILE outcomes
      for the correction of myopic astigmatism associated with a cylinder over 0.75 D,
      and its comparison with the outcomes reported with the excimer laser-based
      corneal refractive surgery techniques. A total of five studies clearly reporting
      SMILE astigmatic outcomes were identified. SMILE shows acceptable outcomes for
      the correction of myopic astigmatism, although a general agreement exists about
      the superiority of the excimer laser-based techniques for low to moderate levels
      of astigmatism. Manual correction of the static cyclotorsion should be adopted
      for any SMILE astigmatic correction over 0.75 D.

PMID- 29167809
TI  - Short-term memory for spatial, sequential and duration information.
AB  - Space and time appear to play key roles in the way that information is organized
      in short-term memory (STM). Some argue that they are crucial contexts within
      which other stored features are embedded, allowing binding of information that
      belongs together within STM. Here we review recent behavioral, neurophysiological
      and imaging studies that have sought to investigate the nature of spatial,
      sequential and duration representations in STM, and how these might break down in
      disease. Findings from these studies point to an important role of the
      hippocampus and other medial temporal lobe structures in aspects of STM,
      challenging conventional accounts of involvement of these regions in only long
      term memory.

PMID- 29167810
TI  - The pre/parasubiculum: a hippocampal hub for scene-based cognition?
AB  - Internal representations of the world in the form of spatially coherent scenes
      have been linked with cognitive functions including episodic memory, navigation
      and imagining the future. In human neuroimaging studies, a specific hippocampal
      subregion, the pre/parasubiculum, is consistently engaged during scene-based
      cognition. Here we review recent evidence to consider why this might be the case.
      We note that the pre/parasubiculum is a primary target of the parieto-medial
      temporal processing pathway, it receives integrated information from foveal and
      peripheral visual inputs and it is contiguous with the retrosplenial cortex. We
      discuss why these factors might indicate that the pre/parasubiculum has
      privileged access to holistic representations of the environment and could be
      neuroanatomically determined to preferentially process scenes.

PMID- 29167811
TI  - Datasets, processing and refinement details for Mtb-AnPRT: inhibitor structures
      with various space groups.
AB  - There are twenty-five published structures of Mycobacterium tuberculosis
      anthranilate phosphoribosyltransferase (Mtb-AnPRT) that use the same
      crystallization protocol. The structures include protein complexed with natural
      and alternative substrates, protein:inhibitor complexes, and variants with
      mutations of substrate-binding residues. Amongst these are varying space groups
      (i.e. P21, C2, P21212, P212121). This article outlines experimental details for 3
      additional Mtb-AnPRT:inhibitor structures. For one protein:inhibitor complex, two
      datasets are presented - one generated by crystallization of protein in the
      presence of the inhibitor and another where a protein crystal was soaked with the
      inhibitor. Automatic and manual processing of these datasets indicated the same
      space group for both datasets and thus indicate that the space group differences
      between structures of Mtb-AnPRT:ligand complexes are not related to the method
      used to introduce the ligand.

PMID- 29167812
TI  - Data for occupancy internal heat gain calculation in main building categories.
AB  - Heat losses from occupant body by means of convection, radiation, vapor, and
      sweat are essential data for indoor climate and energy simulations. Heat losses
      depend on the metabolic activity and body surface area. Higher variations of body
      surface area of occupants are observed in day care centers, kinder gardens and
      schools compared to other building categories (Tables 2 and 3) and these
      variations need to be accounted, otherwise in these building categories heat
      gains, CO2 and humidity generation are overestimated. Indoor temperature,
      humidity level, air velocity, and clothing insulation have significant influences
      on dry and total heat losses from occupant body leading to typical values for
      summer and winter. The data presented in this article are related to the research
      article entitled Occupancy schedules for energy simulation in new prEN16798-1 and
      ISO/FDIS 17772-1 standards (Ahmed et al., 2017) [1].

PMID- 29167813
TI  - Experimental data on load test and performance parameters of a LENZ type vertical
      axis wind turbine in open environment condition.
AB  - Performance and load testing data of a three bladed two stage LENZ type vertical
      axis wind turbine from the experiments conducted in an open environment condition
      at Hindustan Institute of Technology and Science, Chennai (location 23.2167
      degrees N, 72.6833 degrees E) are presented here. Low-wind velocity ranging from
      2 to 11 m/s is available everywhere irrespective of climatic seasons and this
      data provides the support to the researchers using numerical tool to validate and
      develop an enhanced Lenz type design. Raw data obtained during the measurements
      are processed and presented in the form so as to compare with other typical
      outputs. The data is measured at different wind speeds prevalent in the open
      field condition ranging from 3 m/s to 9 m/s.

PMID- 29167814
TI  - Data for the optimization of conditions for meat species identification using
      ultra-fast multiplex direct-convection PCR.
AB  - This article contains data related to the research article entitled "Ultra-fast
      DNA-based multiplex convection PCR method for meat species identification with
      possible on-site applications" (Song et al., 2017 [1]). Direct PCR that does not
      require prior DNA extraction is critical for ultra-fast molecular detection of
      meat species. We successfully acquired DNA by swab sampling in Taq DNA polymerase
      buffer. To reduce DNA sample preparation time, proteinase K incubation (0.2
      MUg/mL) and heat inactivation times were decreased to 10 min and 1 min,
      respectively. The analysis of swabbed DNA samples from mixed meat could
      differentiate meat species within the mixed sample. The swabbed DNA samples could
      be diluted 100 times without losing detection sensitivity.

PMID- 29167815
TI  - The metagenome of bromeliads phytotelma in Puerto Rico.
AB  - Bromeliads tank water or phytotelma is an eutrophic microenvironment where
      microorganisms have evolved to resist sudden changes in pH and nutritional
      competition. Metagenomics studies have been poorly studied in bromeliads and
      environmental DNA (eDNA) characterization for its microenvironment is deficient
      in Puerto Rico. Therefore, the data represents the microbial communities
      inhabiting bromeliads phytotelma. eDNA was extracted using Metagenomic DNA
      Isolation Kit for Water. Next-Generation-Sequencing technology (Illumina MiSeq)
      was used for sequencing the isolated eDNA. This data provides an insight about
      diversity and functional depiction of microorganisms inhabiting bromeliads
      phytotelma. The data of this metagenome is available in the BioSample Submission
      Portal as Bioproject PRJNA39461 and Sequence Read Archive (SRA) accession number
      SRP114300. MG-RAST metagenomic analysis server is located under the study ID
      mgp79812.

PMID- 29167816
TI  - Macroeconomic dataset for generating macroeconomic volatility among selected
      countries in the Asia Pacific region.
AB  - This data article provides macroeconomic data that can be used to generate
      macroeconomic volatility. The data cover a sample of seven selected countries in
      the Asia Pacific region for the period 2004-2014, including both developing and
      developed countries. This dataset was generated to enhance our understanding of
      the sources of macroeconomic volatility affecting the countries in this region.
      Although the Asia Pacific region continues to remain as the most dynamic part of
      the world's economy, it is not spared from various sources of macroeconomic
      volatility through the decades. The reported data cover 15 types of macroeconomic
      data series, representing three broad categories of indicators that can be used
      to proxy macroeconomic volatility. They are indicators that account for
      macroeconomic volatility (i.e. volatility as a macroeconomic outcome), domestic
      sources of macroeconomic volatility and external sources of macroeconomic
      volatility. In particular, the selected countries are Malaysia, Thailand,
      Indonesia and Philippines, which are regarded as developing countries, while
      Singapore, Japan and Australia are developed countries. Despite the differences
      in level of economic development, these countries were affected by similar
      sources of macroeconomic volatility such as the Asian Financial Crisis and the
      Global Financial Crisis. These countries were also affected by other similar
      external turbulence arising from factors such as the global economic slowdown,
      geopolitical risks in the Middle East and volatile commodity prices. Nonetheless,
      there were also sources of macroeconomic volatility which were peculiar to
      certain countries only. These were generally domestic sources of volatility such
      as political instability (for Thailand, Indonesia and Philippines), natural
      disasters and anomalous weather conditions (for Thailand, Indonesia, Philippines,
      Japan and Australia) and over-dependence on the electronic sector (for
      Singapore).

PMID- 29167817
TI  - Data on crystal organization in the structure of the Fab fragment from the NIST
      reference antibody, RM 8671.
AB  - The reported data describe the crystallization, crystal packing, structure
      determination and twinning of the unliganded Fab (antigen-binding fragment) from
      the NISTmAb (standard reference material 8671). The raw atomic coordinates are
      available as Protein Data Bank structure 5K8A and biological aspects are
      described in the article, (Karageorgos et al., 2017) [1]. Crystal data show that
      the packing is unique, and show the basis for the crystal's twinned growth.
      Twinning is a common and often serious problem in protein structure determination
      by x-ray crystallography [2]. In the present case the twinning is due to a small
      deviation (about 0.3 nm) from 4-fold symmetry in the primary intermolecular
      interface. The deviation produces pseudosymmetry, generating slightly different
      conformations of the protein, and alternating strong and weak forms of key
      packing interfaces throughout the lattice.

PMID- 29167818
TI  - A validation dataset for Macaque brain MRI segmentation.
AB  - Validation data for segmentation algorithms dedicated to preclinical images is
      fiercely lacking, especially when compared to the large number of databases of
      Human brain images and segmentations available to the academic community. Not
      only is such data essential for validating methods, it is also needed for
      objectively comparing concurrent algorithms and detect promising paths, as
      segmentation challenges have shown for clinical images. The dataset we present
      here is a first step in this direction. It comprises 10 T2-weighted MRIs of
      healthy adult macaque brains, acquired on a 7 T magnet, along with corresponding
      manual segmentations into 17 brain anatomic labelled regions spread over 5
      hierarchical levels based on a previously published macaque atlas (Calabrese et
      al., 2015) [1]. By giving access to this unique dataset, we hope to provide a
      reference needed by the non-human primate imaging community. This dataset was
      used in an article presenting a new primate brain morphology analysis pipeline,
      Primatologist (Balbastre et al., 2017) [2]. Data is available through a NITRC
      repository (https://www.nitrc.org/projects/mircen_macset).

PMID- 29167820
TI  - Engineering Chimeric Antigen Receptor T cells to Treat Glioblastoma.
AB  - Immunotherapy has emerged as a promising strategy for glioblastoma (GBM), a
      disease that remains universally fatal despite currently available standard-of
      care. Adoptive T cell therapy has been shown to produce potent antitumor immunity
      while obviating the need for traditional antigen presentation and primary immune
      responses. Chimeric antigen receptors (CARs) are specialized molecules that can
      be expressed on the surface of T cells allowing for redirected cytotoxicity
      against tumor antigens of interest. To date, the application of CAR T cells for
      GBM has been relatively limited, in large part due to a dearth of well-described
      tumor specific antigens that are both homogenously and frequently expressed. A
      mutated version of the epidermal growth factor receptor, EGFRvIII, is a
      constitutively activated tyrosine kinase that is expressed on the surface of GBM
      and other common neoplasms, but completely absent from all normal tissues. We
      have recently generated CAR T cells directed against EGFRvIII and reported
      results from a Phase I clinical trial investigating this platform in patients
      with EGFRvIII-expressing GBM. Our study showed that despite conventional notions
      of central nervous system "immune-privilege," EGFRvIII CAR T cells trafficked to
      intracerebral tumors, leading to successful targeting and eradication of this
      antigen in the brain. Here, we review our experience with EGFRvIII CAR T cells
      and highlight important considerations for the clinical translation of this
      therapy in patients with GBM.

PMID- 29167819
TI  - Successful amplification of DNA aboard the International Space Station.
AB  - As the range and duration of human ventures into space increase, it becomes
      imperative that we understand the effects of the cosmic environment on astronaut
      health. Molecular technologies now widely used in research and medicine will need
      to become available in space to ensure appropriate care of astronauts. The
      polymerase chain reaction (PCR) is the gold standard for DNA analysis, yet its
      potential for use on-orbit remains under-explored. We describe DNA amplification
      aboard the International Space Station (ISS) through the use of a miniaturized
      miniPCR system. Target sequences in plasmid, zebrafish genomic DNA, and bisulfite
      treated DNA were successfully amplified under a variety of conditions.
      Methylation-specific primers differentially amplified bisulfite-treated samples
      as would be expected under standard laboratory conditions. Our findings establish
      proof of concept for targeted detection of DNA sequences during spaceflight and
      lay a foundation for future uses ranging from environmental monitoring to on
      orbit diagnostics.

PMID- 29167821
TI  - PTK6 regulates growth and survival of endocrine therapy-resistant ER+ breast
      cancer cells.
AB  - The non-receptor tyrosine kinase, PTK6/BRK, is highly expressed in multiple tumor
      types, including prostate, ovarian, and breast cancers, and regulates oncogenic
      phenotypes such as proliferation, migration, and survival. PTK6 inhibition also
      overcomes targeted therapy resistance of HER2+ breast cancer. Although PTK6 is
      highly expressed in ER+ Luminal breast cancers, the role of PTK6 in this subtype
      has not been elucidated. In this study, we investigated the functions of PTK6 in
      ER+ Luminal breast cancer cells, including those that are relatively resistant to
      estrogen deprivation or targeted endocrine therapies used in the treatment of ER+
      cancers. Enhanced expression of PTK6 in ER+ breast cancer cells enhances growth
      of ER+ breast cancer cells, including tamoxifen-treated cells. Downregulation of
      PTK6 in ER+ breast cancer cells, including those resistant to tamoxifen,
      fulvestrant, and estrogen deprivation, induces apoptosis, as evidenced by
      increased levels of cleaved PARP, and an increase in the AnnexinV+ population.
      PTK6 downregulation impairs growth of these cells in 3D MatrigelTM cultures, and
      virtually abrogates primary tumor growth of both tamoxifen-sensitive and
      resistant MCF-7 xenografts. Finally, we show that p38 MAPK activation is critical
      for PTK6 downregulation-induced apoptosis, a mechanism that we previously
      reported for survival of HER2+ breast cancer cells, highlighting conserved
      mechanisms of survival regulation by PTK6 across breast cancer subtypes. In
      conclusion, our studies elucidate critical functions of PTK6 in ER+ Luminal
      breast cancers and support PTK6 as an attractive therapeutic target for ER+
      breast cancers.

PMID- 29167822
TI  - Two-dimensional limit of crystalline order in perovskite membrane films.
AB  - Long-range order and phase transitions in two-dimensional (2D) systems-such as
      magnetism, superconductivity, and crystallinity-have been important research
      topics for decades. The issue of 2D crystalline order has reemerged recently,
      with the development of exfoliated atomic crystals. Understanding the dimensional
      limit of crystalline phases, with different types of bonding and synthetic
      techniques, is at the foundation of low-dimensional materials design. We study
      ultrathin membranes of SrTiO3, an archetypal perovskite oxide with isotropic (3D)
      bonding. Atomically controlled membranes are released after synthesis by
      dissolving an underlying epitaxial layer. Although all unreleased films are
      initially single-crystalline, the SrTiO3 membrane lattice collapses below a
      critical thickness (5 unit cells). This crossover from algebraic to exponential
      decay of the crystalline coherence length is analogous to the 2D topological
      Berezinskii-Kosterlitz-Thouless (BKT) transition. The transition is likely driven
      by chemical bond breaking at the 2D layer-3D bulk interface, defining an
      effective dimensional phase boundary for coherent crystalline lattices.

PMID- 29167823
TI  - Apelin Gene Therapy Increases Autophagy via Activation of Sirtuin 3 in Diabetic
      Heart.
AB  - Heart failure is the leading cause of death in diabetic patients. Recently we
      showed that apelin gene therapy attenuates heart failure following myocardial
      infarction. This study further explored the potential mechanisms by which apelin
      may reduce cardiac injury in Postmyocardial infarction (MI)) model of diabetes.
      Wild type and Sirt3 knockout (Sirt3 KO) mice were induced into diabetes by intra
      peritoneal (i.p.) Streptozotocin (STZ). STZ mice were then subjected to MI
      followed by immediate intramyocardial injection with Adenovirus-apelin (Ad
      apelin). Ad-apelin treatment resulted in over expression of apelin in the
      ischemic hearts of STZ mice. Apelin over expression led to a significant increase
      in Sirt3 expression. Apelin over expression significantly reduced gp91phox
      expression. This was accompanied by a significant reduction of reactive oxygen
      species formation. Ad-apelin treatment also dramatically reduced NF-kappab-p65
      expression in WT-STZ mice. Over expression of apelin further enhanced autophagy
      markers (LC3-II and beclin-1) expression in post-MI heart. Most intriguingly,
      knockout of Sirt3 in STZ mice abolished these beneficial effects of apelin
      treatment. In vitro, knockout of Sirt3 in EPCs significantly enhanced high
      glucose-induced ROS formation. Conversely, treatment of Sirt3 KO-EPCs with NADPH
      oxidase inhibitor led to two fold increase in LC3-II levels. Our studies
      demonstrate that apelin increases autophagy via up regulation of Sirt3 and
      suppression of ROS-NF-kappab pathway in diabetic heart.

PMID- 29167824
TI  - Protein activation mapping of human sun-protected epidermis after an acute dose
      of erythemic solar simulated light.
AB  - Ultraviolet radiation is an important etiologic factor in skin cancer and a
      better understanding of how solar stimulated light (SSL) affects signal
      transduction pathways in human skin which is needed in further understanding
      activated networks that could be targeted for skin cancer prevention. We utilized
      Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that
      allows for broad-scale and quantitative measurement of the
      activation/phosphorylation state of hundreds of key signaling proteins and
      protein pathways in sun-protected skin after an acute dose of two minimal
      erythema dose (MED) of SSL. RPPA analysis was used to map the altered cell
      signaling networks resulting from acute doses of solar simulated radiation (SSL).
      To that end, we exposed sun-protected skin in volunteers to acute doses of two
      MED of SSL and collected biopsies pre-SSL and post-SSL irradiation. Frozen
      biopsies were subjected to laser capture microdissection (LCM) and then assessed
      by RPPA. The activation/phosphorylation or total levels of 128 key signaling
      proteins and drug targets were selected for statistical analysis. Coordinate
      network-based analysis was performed on specific signaling pathways that included
      the PI3k/Akt/mTOR and Ras/Raf/MEK/ERK pathways. Overall, we found early and
      sustained activation of the PI3K-AKT-mTOR and MAPK pathways. Cell death and
      apoptosis-related proteins were activated at 5 and 24 h. Ultimately, expression
      profile patterns of phosphorylated proteins in the epidermal growth factor
      receptor (EGFR), AKT, mTOR, and other relevant pathways may be used to determine
      pharmacodynamic activity of new and selective topical chemoprevention agents
      administered in a test area exposed to SSL to determine drug-induced attenuation
      or reversal of skin carcinogenesis pathways.

PMID- 29167825
TI  - An epidemiological survey of porcine cysticercosis in Nyasa District, Ruvuma
      Region, Tanzania.
AB  - Porcine cysticercosis (PC) caused by Taenia solium larvae is continuing being
      important zoonotic disease in many developing countries. It poses a serious
      public health risk and leads to economic losses to pig production industry. This
      study was carried out to determine the prevalence and risk factors associated
      with PC transmission in Nyasa District. To establish the prevalence of PC, a
      cross-sectional survey was conducted involving 698 pigs by tongue examination,
      330 pigs by Ag-ELISA test and 22 pigs by meat inspection. A questionnaire survey
      was administered to a member of selected households to gather information on pig
      management and other potential factors that could explain the prevalence of PC in
      the area. Results showed that 44 pigs were positive by tongue examination (6.3%,
      95% C.I. 4.5-8.1%), 110 tested positive for Ag-ELISA (33.3%, 95% C.I. 28.22
      38.38%) and meat inspection detected four infected pigs (18.2%, 95% C.I. 2.08
      34.32%). Risk factors associated with PC transmission in Nyasa District were free
      ranging of pigs (p = 0001), sex of pig (p = 0.011), source of pork (p = 0.0001)
      and outdoor defecation (0.0001). The present findings indicate that PC is endemic
      in Nyasa District and that free-ranging of pigs in conjunction with limited use
      of latrines contributes significantly to PC transmission. Therefore, mandatory
      pig confinement, together with use of latrine/toilets should be considered in
      controlling PC in Nyasa District.

PMID- 29167826
TI  - Efficient in vitro delivery of Noggin siRNA enhances osteoblastogenesis.
AB  - Several types of serious bone defects would not heal without invasive clinical
      intervention. One approach to such defects is to enhance the capacity of bone
      formation cells. Exogenous bone morphogenetic proteins (BMP) have been utilized
      to positively regulate matrix mineralization and osteoblastogenesis, however,
      numerous adverse effects are associated with this approach. Noggin, a potent
      antagonist of BMPs, is an ideal candidate to target and decrease the need for
      supraphysiological doses of BMPs. In the current research we report a novel siRNA
      mediated gene knock-down strategy to down-regulate Noggin. We utilized a lipid
      nanoparticle (LNP) delivery strategy in pre-osteoblastic rat cells. In vitro LNP
      siRNA treatment caused inconsequential cell toxicity and transfection was
      achieved in over 85% of cells. Noggin siRNA treatment successfully down-regulated
      cellular Noggin protein levels and enhanced BMP signal activity which in turn
      resulted in significantly increased osteoblast differentiation and extracellular
      matrix mineralization evidenced by histological assessments. Gene expression
      analysis showed that targeting Noggin specifically in bone cells would not lead
      to a compensatory effect from other BMP negative regulators such as Gremlin and
      Chordin. The results from this study support the notion that novel therapeutics
      targeting Noggin have the clinically relevant potential to enhance bone formation
      without the need for toxic doses of exogenous BMPs. Such treatments will
      undeniably provide safe and economical treatments for individuals whose poor bone
      repair results in permanent morbidity and disability.

PMID- 29167828
TI  - The big, the bad, and the exon 11: adjuvant imatinib for all gastro-intestinal
      stromal tumors or just the ugly?

PMID- 29167829
TI  - Hepatocellualr cancer and liver transplantation: from the tower of babel towards
      a uniform language.

PMID- 29167827
TI  - Hepatocellular cancer and recurrence after liver transplantation: what about the
      impact of immunosuppression?
AB  - Liver transplantation (LT) has originally been designed to treat hepatobiliary
      malignancies. The initial results of LT for hepatocellular cancer (HCC) were,
      however, dismal this mainly due to the poor patient selection procedure. Better
      surgical and perioperative care and, especially, the refinement of selection
      criteria led to a major improvement of results, making HCC nowadays (again!) one
      of the leading indications for LT. This evolution is clearly shown by the
      innumerable reports aiming to further extend inclusion criteria for LT in HCC
      patients. Nonetheless, the vast majority of papers only deals with morphologic
      (tumour diameter and number) and (only recently) biologic (tumour markers and
      response to locoregional treatment) parameters to do so. Curiously enough, the
      role of both the immune competent state of the recipient as well as the impact of
      both immunosuppression (IS) type and load has been very poorly addressed in this
      context, even if it has been shown for a long time, based on both basic and
      clinical research, that they all play a key role in the outcome of any oncologic
      treatment and in the development of de novo as well as recurrent tumours. This
      chapter aims to give, after a short introductive note about the currently used
      inclusion criteria of HCC patients for LT and about the role of IS in
      carcinogenesis, a comprehensive overview of the actual literature related to the
      impact of different immunosuppressive drugs and schemes on outcome of LT in HCC
      recipients. Unfortunately, up to now solid conclusions cannot be drawn due to the
      lack of high-level evidence studies caused by the heterogeneity of the studied
      patient cohorts and the lack of prospectively designed and randomized studies.
      Based on long-term personal experience with immunosuppressive handling in LT some
      proposals for further clinical research and practice are put forward. The
      strategy of curtailing and minimising IS should be explored in the growing field
      of transplant oncology taking thereby into account the immunological privilege of
      the liver allograft. These strategies will become more and more compelling when
      further extending the indications in which adjuvant chemotherapy will probably
      become an inherent part of the therapeutic scheme of HCC liver recipients.

PMID- 29167830
TI  - Single injection dual phase CBCT technique ameliorates results of trans-arterial
      chemoembolization for hepatocellular cancer.
AB  - Cone-beam CT (CBCT) application to the field of trans-arterial chemoembolization
      has been recently the focus of several researches. This imaging modality is
      performed with a rotation of the C-arm around the patient, without needs of
      patient repositioning. Datasets are immediately processed, obtaining volumetric
      CT-like images with the possibility of post-processing and reconstruction of
      images. Dual phase CBCT recently introduced in clinical practice consists in a
      first arterial acquisition followed by a delayed acquisition corresponding to a
      venous phase. The introduction of this feature has overcome the limit of single
      phase acquisitions, allowing lesions characterization. Moreover these recent
      advantages have several intra-procedural implications. Detailed technical and
      acquisition parameters will be widely exposed in this review with particular
      attention to: catheter positioning, acquisition delay, injection parameters,
      patient positioning and contrast dilution. Comparison with standard of practice
      second line imaging [multidetector computer tomography (MDCT) and
      MDCT/arteriography] demonstrate the capability of detecting occult nodules
      providing some clinical implications thus potentially identifying a sub set of
      patients with aggressive disease behaviour. Other intra-procedural advantages of
      dual phase CBCT usage consist in a better tumor feeder visualization, reduction
      of proper DSA and fluoroscopic time, suggestion the presence of an extrahepatic
      parasitic feeder thus resulting in a more accurate treatment. Finally, the
      volumetrical intraprocedural evaluation of accumulation of embolic agent has
      proved to be correlate with treatment response if compared with MRI.

PMID- 29167831
TI  - Laparoscopic distal gastrectomy with D2 lymphadenectomy followed by
      intracorporeal gastroduodenostomy for advanced gastric cancer: technical guide
      and tips.
AB  - In 1994, Kitano and colleagues first reported laparoscopy-assisted Billroth I
      gastrectomy. Since then, laparoscopic gastrectomy (LG) has been associated with
      earlier patient recovery compared with open surgery, and has gained increasing
      international acceptance. Japan Society of Endoscopic Surgery biennial surveys
      confirm the increasing use of laparoscopic procedures for treatment of gastric
      cancer in Japan. Its thirteenth national survey indicates that of 31,264 patients
      treated at Japanese institutions in 2015, approximately 9,500 (30.3%) underwent
      LG, and laparoscopic distal gastrectomy (LDG) was the procedure most commonly
      performed. Despite evidence supporting the efficacy of LDG for gastric cancer in
      the short term, however, uncertainty remains concerning the efficacy of LG.
      Today, phase III randomized control trials on this procedure are ongoing in East
      Asian countries. Distal gastrectomy (DG) is the most commonly performed mode of
      resection, and as appropriate surgical techniques need to be acquired by gastric
      surgeons, here we describe a 'gold standard' method to perform total LDG.

PMID- 29167832
TI  - Assessment of nutritional status in laparoscopic gastrectomy for gastric cancer.
AB  - Malnutrition is very common in gastric cancer patients and can be detected in up
      to 85% of patients with gastric cancer. Malnutrition is associated with increased
      morbidity and mortality, prolonged hospital stay, poor treatment tolerance, and
      lower survival rate. Malnutrition also has an impact on quality of life. The
      early detection of nutritional risk with appropriate nutritional care can
      significantly reduce patient's postoperative morbidity and mortality. Because
      there is no gold standard tool, appropriate tools should be selected and applied
      depending on one's institutional conditions. And, it is recommended that
      nutritional assessment should be achieved for every patient at pre/post-operative
      period.

PMID- 29167833
TI  - Disorder-Specific and Shared Brain Abnormalities During Vigilance in Autism and
      Obsessive-Compulsive Disorder.
AB  - Background: Autism spectrum disorder (ASD) and obsessive-compulsive disorder
      (OCD) are often comorbid and share similarities across some cognitive phenotypes,
      including certain aspects of attention. However, no functional magnetic resonance
      imaging studies have compared the underlying neural mechanisms contributing to
      these shared phenotypes. Methods: Age- and IQ-matched boys (11-17 years old) with
      ASD (n = 20), boys with OCD (n = 20), and healthy control boys (n = 20) performed
      a parametrically modulated psychomotor vigilance functional magnetic resonance
      imaging task. Brain activation and performance were compared among adolescents
      with OCD, adolescents with ASD, and control adolescents. Results: Whereas boys
      with ASD and OCD were not impaired on task performance, there was a significant
      group by attention load interaction in several brain regions. With increasing
      attention load, left inferior frontal cortex/insula and left inferior parietal
      lobe/pre/post-central gyrus were progressively less activated in boys with OCD
      relative to the other two groups. In addition, boys with OCD showed progressively
      increased activation with increasing attention load in rostromedial
      prefrontal/anterior cingulate cortex relative to boys with ASD and control boys.
      Shared neurofunctional abnormalities between boys with ASD and boys with OCD
      included increased activation with increasing attention load in cerebellum and
      occipital regions, possibly reflecting increased default mode network activation.
      Conclusions: This first functional magnetic resonance imaging study to compare
      boys with ASD and OCD showed shared abnormalities in posterior cerebellar
      occipital brain regions. However, boys with OCD showed a disorder-specific
      pattern of reduced activation in left inferior frontal and temporo-parietal
      regions but increased activation of medial frontal regions, which may potentially
      be related to neurobiological mechanisms underlying cognitive and clinical
      phenotypes of OCD.

PMID- 29167834
TI  - Hypoactivation and Dysconnectivity of a Frontostriatal Circuit During Goal
      Directed Planning as an Endophenotype for Obsessive-Compulsive Disorder.
AB  - Background: The symptoms of obsessive-compulsive disorder (OCD) have been
      postulated to result from impaired executive functioning and excessive habit
      formation at the expense of goal-directed control and have been objectively
      demonstrated using neuropsychological tests in such patients. This study tested
      whether there is functional hypoactivation as well as dysconnectivity of discrete
      frontostriatal pathways during goal-directed planning in patients with OCD and in
      their unaffected first-degree relatives. Methods: In total, 21 comorbidity-free
      patients with OCD, 19 clinically asymptomatic first-degree relatives of these
      patients, and 20 control participants were tested on a functional magnetic
      resonance optimized version of the Tower of London task. Group differences in
      brain activation during goal-directed planning were measured together with
      associated frontostriatal functional connectivity. Results: Patients with OCD and
      their clinically asymptomatic relatives manifested hypoactivation of the right
      dorsolateral prefrontal cortex during goal-directed planning coupled with reduced
      functional connectivity between this cortical region and the basal ganglia
      (putamen). Conclusions: Hypoactivation of cortical regions associated with goal
      directed planning and associated frontostriatal dysconnectivity represent a
      candidate endophenotype for OCD. These findings accord with abnormalities in
      neural networks supporting the balance between goal-directed and habitual
      behavior, with implications for recent neuropsychological theories of OCD and the
      major neurobiological model for this disorder.

PMID- 29167835
TI  - Sensitizing Clostridium difficile Spores with Germinants on Skin and
      Environmental Surfaces Represents a New Strategy for Reducing Spores via Ambient
      Mechanisms.
AB  - Background: Clostridium difficile is a leading cause of healthcare-associated
      infections worldwide. Prevention of C. difficile transmission is challenging
      because spores are not killed by alcohol-based hand sanitizers or many commonly
      used disinfectants. One strategy to control spores is to induce germination,
      thereby rendering the spores more susceptible to benign disinfection measures and
      ambient stressors. Methods/Results: C. difficile spores germinated on skin after
      a single application of cholic acid-class bile salts and co-germinants; for 4 C.
      difficile strains, recovery of viable spores from skin was reduced by ~0.3
      log10CFU to 2 log10CFU after 2 hours and ~1 log10CFU to > 2.5 log10CFU after 24
      hours. The addition of taurocholic acid to 70% and 30% ethanol significantly
      enhanced reduction of viable spores on skin and on surfaces. Desiccation, and to
      a lesser extent the presence of oxygen, were identified as the stressors
      responsible for reductions of germinated spores on skin and surfaces.
      Additionally, germinated spores became susceptible to killing by pH 1.5
      hydrochloric acid, suggesting that germinated spores that remain viable on skin
      and surfaces might be killed by gastric acid after ingestion. Antibiotic-treated
      mice did not become colonized after exposure to germinated spores, whereas 100%
      of mice became colonized after exposure to the same quantity of dormant spores.
      Conclusions: Germination could provide a new approach to reduce C. difficile
      spores on skin and in the environment and to render surviving spores less capable
      of causing infection. Our findings suggest that it may be feasible to develop
      alcohol-based hand sanitizers containing germinants that reduce spores on hands.

PMID- 29167836
TI  - Optical spin transfer and spin-orbit torques in thin film ferromagnets.
AB  - We study the optically induced torques in thin film ferromagnetic layers under
      excitation by circularly polarized light. We study cases both with and without
      Rashba spin-orbit coupling using a 4-band model. In the absence of Rashba spin
      orbit coupling, we derive an analytic expression for the optical torques,
      revealing the conditions under which the torque is mostly derived from optical
      spin transfer torque (i.e. when the torque is along the direction of optical
      angular momentum), versus when the torque is derived from the inverse Faraday
      effect (i.e. when the torque is perpendicular to the optical angular momentum).
      We find the optical spin transfer torque dominates provided that the excitation
      energy is far away from band edge transitions, and the magnetic exchange
      splitting is much greater than the lifetime broadening. For the case with large
      Rashba spin-orbit coupling and out-of-plane magnetization, we find the torque is
      generally perpendicular to the photon angular momentum and is ascribed to an
      optical Edelstein effect.

PMID- 29167837
TI  - Neighborhood and Individual Sociodemographic Characteristics Associated with
      Disparities in Adult Obesity and Perceptions of the Home Food Environment.
AB  - Purpose: Multiple studies have demonstrated significant disparities in the
      relationship between individual sociodemographic characteristics and risk of
      overweight or obesity. However, little information is available for assessing the
      complex associations among being overweight or obese with neighborhood and
      individual sociodemographic factors and the measured and perceived community food
      environment. Methods: Using 2014 national evaluation data from 20 communities
      (analyzed 2015-2016) that participated in the U.S. Centers for Disease Control
      and Prevention Community Transformation Grants Program, we used multilevel
      multivariable models to assess associations among factors at the individual,
      census tract, and county levels with being overweight or obese and with the
      perceived home food environment. Results: Individual level factors (age, sex,
      race/ethnicity, household income, and education) were significantly associated
      with the likelihood of being overweight or obese in every model tested. Census
      tract level poverty and education were significantly associated with the
      likelihood of being overweight or obese in univariate but not multivariable
      analyses. Perceived community food environment was a significant predictor of the
      perceived home food environment; the objective measure of county-level grocery
      store access was not. Neither perceived nor objective community food environment
      measures were significantly associated with overweight/obesity in multivariable
      analyses. Conclusion: Individual-level sociodemographic characteristics are more
      strongly associated with obesity-related outcomes than are area-level measures.
      Future interventions designed to address health equity issues in obesity among
      underserved populations may benefit from focusing on nutrition education tailored
      to individuals, to encourage purchase and consumption of healthy food. Improving
      healthy food availability in underserved communities may also be critical for
      nutrition education to have a meaningful impact.

PMID- 29167838
TI  - YY1 controls EMU-3'RR DNA loop formation and immunoglobulin heavy chain class
      switch recombination.

PMID- 29167839
TI  - Early-life exposure to indoor air pollution or tobacco smoke and lower
      respiratory tract illness and wheezing in African infants: a longitudinal birth
      cohort study.
AB  - Background: Indoor air pollution (IAP) and environmental tobacco smoke (ETS) are
      associated with lower respiratory tract illness (LRTI) or wheezing in children.
      However, the effect of the timing of these exposures, specifically antenatal
      versus postnatal, and of alternate fuel sources such as the increasingly used
      volatile organic compounds have not been well studied. We longitudinally
      investigated the effect of antenatal or postnatal IAP and ETS on LRTI or wheezing
      prevalence and severity in African infants. Methods: Mother and infant pairs
      enrolled over a 3-year period in a birth cohort study in two centres in Paarl,
      South Africa, were followed for the first year of life for LRTI or wheezing
      illness. We measured exposure to IAP (particulate matter, nitrogen dioxide,
      sulphur dioxide, carbon monoxide, and volatile organic compounds benzene and
      toluene) using devices placed in homes, antenatally and postnatally. We measured
      ETS longitudinally by maternal self-report and by urine cotinine measures. Study
      staff trained in recognition of LRTI or wheeze documented all episodes, which
      were categorised according to WHO case definition criteria. We used multivariate
      logistic and Poisson regressions to explore associations. Findings: Between March
      1, 2012, and March 31, 2015, we enrolled 1137 mothers with 1143 livebirths. Of
      1065 infants who attended at least one study visit, 524 episodes of LRTI occurred
      after discharge with a wheezing prevalence of 0.23 (95% CI 0.21-0.26) episodes
      per child year. Exposures associated with LRTI were antenatal maternal smoking
      (incidence rate ratio 1.62, 95% CI 1.14-2.30; p=0.004) or particulate matter
      (1.43, 1.06-1.95; p=0.008). Subanalyses of LRTI requiring hospitalisation (n=137)
      and supplemental oxygen (n=69) found antenatal toluene significantly increased
      the risk of LRTI-associated hospitalisation (odds ratio 5.13, 95% CI 1.43-18.36;
      p=0.012) and need for supplemental oxygen (13.21, 1.96-89.16; p=0.008). Wheezing
      illness was associated with both antenatal (incidence rate ratio 2.09, 95% CI
      1.54-2.84; p<0.0001) and postnatal (1.27, 95% CI 1.03-1.56; p=0.024) maternal
      smoking. Antenatally, wheezing was associated with maternal passive smoke
      exposure (1.70, 1.25-2.31; p=0.001) and, postnatally, with any household member
      smoking (1.55, 1.17 -2.06; p=0.002). Interpretation: Antenatal exposures were the
      predominant risk factors associated with LRTI or wheezing illness. Toluene was a
      novel exposure associated with severe LRTI. Urgent and effective interventions
      focusing on antenatal environmental factors are required, including smoking
      cessation programmes targeting women of childbearing age pre-conception and
      pregnant women. Funding: Bill & Melinda Gates Foundation, Discovery Foundation,
      South African Thoracic Society AstraZeneca Respiratory Fellowship, Medical
      Research Council South Africa, National Research Foundation South Africa, and
      CIDRI Clinical Fellowship.

PMID- 29167840
TI  - Intracranial Volume Quantification from 3D Photography.
AB  - 3D photography offers non-invasive, radiation-free, and anesthetic-free
      evaluation of craniofacial morphology. However, intracranial volume (ICV)
      quantification is not possible with current non-invasive imaging systems in order
      to evaluate brain development in children with cranial pathology. The aim of this
      study is to develop an automated, radiation-free framework to estimate ICV. Pairs
      of computed tomography (CT) images and 3D photographs were aligned using
      registration. We used the real ICV calculated from the CTs and the head volumes
      from their corresponding 3D photographs to create a regression model. Then, a
      template 3D photograph was selected as a reference from the data, and a set of
      landmarks defining the cranial vault were detected automatically on that
      template. Given the 3D photograph of a new patient, it was registered to the
      template to estimate the cranial vault area. After obtaining the head volume, the
      regression model was then used to estimate the ICV. Experiments showed that our
      volume regression model predicted ICV from head volumes with an average error of
      5.81 +/- 3.07% and a correlation (R2) of 0.96. We also demonstrated that our
      automated framework quantified ICV from 3D photography with an average error of
      7.02 +/- 7.76%, a correlation (R2) of 0.94, and an average estimation error for
      the position of the cranial base landmarks of 11.39 +/- 4.3mm.

PMID- 29167841
TI  - Formal total synthesis of the akuammiline alkaloid (+)-strictamine.
AB  - An asymmetric formal total synthesis of the akuammiline alkaloid (+)-strictamine
      is reported. The key features of the synthesis include a Friedel-Crafts
      cyclization to form the D-ring and the critical C7 all-carbon quaternary carbon
      centre, as well as an aza-1,6-conjugate addition to assemble the 2
      azabicyclo[3.3.1]nonane system.

PMID- 29167842
TI  - Enhanced solar absorption and visible-light photocatalytic and
      photoelectrochemical properties of aluminium-reduced BaTiO3 nanoparticles.
AB  - Enhanced solar light absorption and photocatalytic and photoelectrochemical
      properties have been achieved in black BaTiO3 with a unique core/shell structure
      (crystalline BaTiO3@amorphous BaTiO3-x) using an Al-reduction method. This
      finding may open a new avenue to tune the inert ferroelectric materials toward
      excellent photocatalysts for advanced applications.

PMID- 29167844
TI  - Recellularization of decellularized adipose tissue-derived stem cells: role of
      the cell-secreted extracellular matrix in cellular differentiation.
AB  - Adipose-derived stem cells (ASCs) are found in a location within the adipose
      tissue known as the stem cell niche. The ASCs in the niche are maintained in the
      quiescent state, and upon exposure to various microenvironmental triggers are
      prompted to undergo proliferation or differentiation. These microenvironmental
      triggers also modulate the extracellular matrix (ECM), which interacts with the
      cells through the cytoskeleton and induces downstream events inside the cells
      that bring about a change in cell behaviour. In response to these changes, the
      cells remodel the ECM, which will differ according to the type of tissue being
      formed by the cells. As the ECM itself plays an important role in the regulation
      of cellular differentiation, this study aims to explore the role of the cell
      secreted ECM at various stages of differentiation of stem cells in triggering the
      differentiation of ASCs. To this end, the ASCs cultured in proliferation,
      osteogenic and adipogenic media were decellularized and the secreted ECM was
      characterized. Overall, it was found that osteo-differentiated ASCs produced
      higher amounts of collagen and glycosaminoglycans (GAG) compared to the
      undifferentiated and adipo-differentiated ASCs. The two types of differentiated
      ECMs were subsequently shown to trigger initial but not terminal differentiation
      of ASCs into osteo- and adipo-lineages respectively, as indicated by the
      upregulation of lineage specific markers. In addition, integrin subunits alpha
      (alpha) 6 and integrin beta (beta) 1 were found to be produced by ASCs cultured
      on cell-secreted ECM-coated substrates, suggesting that the integrins alpha6 and
      beta1 play an instrumental role in cell-ECM interactions. Taken together, this
      study demonstrates the importance of the ECM in cellular fate decisions and how
      ECM-coated substrates can potentially be used for various tissue engineering
      applications.

PMID- 29167846
TI  - A combinatorial immunoassay for multiple biomarkers via a stable isotope tagging
      strategy.
AB  - A combinatorial immunoassay method for biomarker detection based on a stable
      isotope tagging strategy was proposed. A multiplex immunoassay of 12 proteins
      could be achieved simultaneously and a combinatorial immunoassay was explored,
      which would be expected to satisfy the requirements of personalized detection.

PMID- 29167847
TI  - Fluorescent nanoparticles from mature vinegar: their properties and interaction
      with dopamine.
AB  - Naturally occurring nanoparticles may be present in food. In this paper we report
      the discovery of fluorescent nanoparticles (FNs) in Chinese mature vinegar. The
      physicochemical properties of these FNs were investigated. The FNs were shown to
      emit bright blue fluorescence under the irradiation of ultraviolet light, with a
      fluorescence quantum yield of 5.71%. They are highly soluble in aqueous solution,
      and exhibit excitation-dependent emission behavior. TEM characterization showed
      that the average size of FNs is about 1.40 +/- 0.40 nm, and the morphology of FNs
      is mainly spherical. The physicochemical properties of FNs are similar to those
      of artificially synthesized carbon dots. Furthermore, the interaction between FNs
      and dopamine was studied, and the fluorescence of FNs varied gradually from a
      blue, to a cyan and finally to a green color with increasing dopamine
      concentration. The fluorescence decay dynamics revealed that Forster resonance
      energy transfer (FRET) occurred between the FNs and polymerized dopamine. This
      result suggests that the FNs from Chinese mature vinegar can interact with
      dopamine, which may add a new perspective to the potential health implications of
      foodborne nanoparticles.

PMID- 29167848
TI  - Silver-catalyzed decarboxylative C(sp2)-C(sp3) coupling reactions via a radical
      mechanism.
AB  - A silver catalyzed decarboxylative C(sp2)-C(sp3) coupling of vinylic carboxylic
      acids with alcohols, alkylbenzenes, cycloalkanes and cyclic ethers was developed
      by using DTBP as an oxidant. This reaction tolerates a wide range of substrates,
      and products are obtained in good to excellent yields. The reaction also shows
      good stereoselectivity, and only trans-isomers are obtained. In addition, a
      radical pathway would be involved to facilitate this decarboxylative C(sp2)
      C(sp3) coupling reaction.

PMID- 29167849
TI  - Identifying DNA mismatches at single-nucleotide resolution by probing individual
      surface potentials of DNA-capped nanoparticles.
AB  - Here, we demonstrate a powerful method to discriminate DNA mismatches at single
      nucleotide resolution from 0 to 5 mismatches (chi0 to chi5) using Kelvin probe
      force microscopy (KPFM). Using our previously developed method, we quantified the
      surface potentials (SPs) of individual DNA-capped nanoparticles (DCNPs, ~100 nm).
      On each DCNP, DNA hybridization occurs between ~2200 immobilized probe DNA (pDNA)
      and target DNA with mismatches (tDNA, ~80 nM). Thus, each DCNP used in the
      bioassay (each pDNA-tDNA interaction) corresponds to a single ensemble in which a
      large number of pDNA-tDNA interactions take place. Moreover, one KPFM image can
      scan at least dozens of ensembles, which allows statistical analysis (i.e., an
      ensemble average) of many bioassay cases (ensembles) under the same conditions.
      We found that as the chin increased from chi0 to chi5 in the tDNA, the average SP
      of dozens of ensembles (DCNPs) was attenuated owing to fewer hybridization events
      between the pDNA and the tDNA. Remarkably, the SP attenuation vs. the chin showed
      an inverse-linear correlation, albeit the equilibrium constant for DNA
      hybridization exponentially decreased asymptotically as the chin increased. In
      addition, we observed a cascade reaction at a 100-fold lower concentration of
      tDNA (~0.8 nM); the average SP of DCNPs exhibited no significant decrease but
      rather split into two separate states (no-hybridization vs. full-hybridization).
      Compared to complementary tDNA (i.e., chi0), the ratio of no-hybridization/full
      hybridization within a given set of DCNPs became ~1.6 times higher in the
      presence of tDNA with single mismatches (i.e., chi1). The results imply that our
      method opens new avenues not only in the research on the DNA hybridization
      mechanism in the presence of DNA mismatches but also in the development of a
      robust technology for DNA mismatch detection.

PMID- 29167851
TI  - What regulates the catalytic activities in AGE catalysis? An answer from quantum
      mechanics/molecular mechanics simulations.
AB  - The AGE superfamily (AGEs) is made up of kinds of isomerase which are very
      important both physiologically and industrially. One of the most intriguing
      aspects of AGEs has to do with the mechanism that regulates their activities in
      single conserved active pocket. In order to clarify the relationship among single
      conserved active pocket and two activities in AGEs, results for the epimerization
      activity catalyzed by RaCE and the isomerization activity catalyzed by SeYihS
      were obtained by using QM/MM umbrella sampling simulations and 2D-FES
      calculations. Our results show that both of them have similar enzyme-substrate
      combination mode for inner pyranose ring in single conserved active pocket even
      though they have different substrate specificity. This means that the pathways of
      ring opening catalyzed by them are similar. However, one non-conserved residue
      (Leu183 in RaCE, Met175 in SeYihS) in the active site, which has different steric
      hindrance, causes a small but effective change in the direction of ring opening
      in stage 1. And then this change will induce a fundamentally different catalytic
      activity for RaCE and SeYihS in stage 2. Our results give a novel viewpoint about
      the regulatory mechanism between CE and YihS in AGEs, and may be helpful for
      further experiments of rational enzyme design based on the (alpha/alpha)6-barrel
      basic scaffold.

PMID- 29167852
TI  - A novel thermo-responsive supramolecular organogel based on dual acylhydrazone:
      fluorescent detection for Al3+ ions.
AB  - A new dual acylhydrazone-functionalized gelator (L) has been synthesized, which
      behaves as a thermal-responsive supramolecular organogel (L-gel) in DMSO. This L
      gel exhibits very weak fluorescence based on the photoinduced electron transfer
      (PET) mechanism. The L-gel can recognize Al3+ and assemble into an enhanced blue
      light-emitting supramolecular metallogel (Al@gel).

PMID- 29167855
TI  - Na2S-mediated synthesis of terminal alkynes from gem-dibromoalkenes.
AB  - The Na2S-mediated facile synthesis of terminal alkynes from gem-dibromoalkenes,
      at 20/40  degrees C under open flask conditions has been developed. Various
      precursors derived from heteroaromatic/aromatic/aliphatic aldehydes were found
      compatible. The reaction is proposed to proceed through the Fritsch-Buttenberg
      Wiechell (FBW) rearrangement involving the corresponding vinyl carbene. Using
      mild reaction conditions with inexpensive Na2S.9H2O under air atmosphere has
      significant advantages over earlier routes.

PMID- 29167856
TI  - Styrylisoxazole-based fluorescent probes for the detection of hydrogen sulfide.
AB  - Styrylisoxazoles bearing a nitro group linked to bulky aromatic rings have been
      synthesized and examined for their absorption and emission studies in organic
      solvents and water. The molecules showed emission in the visible region with
      significant solvatochromic emission shifts influenced by the extended conjugation
      of aromatic rings and intramolecular charge transfer. These absorption and
      emission changes were used for the efficient and sensitive detection of trace
      concentrations of hydrogen sulfide (H2S) through the reduction of the nitro group
      to the amine group in the presence of aqueous sodium sulfide. The experimental
      results indicated that the probes exhibit an excellent emission response with
      large shifts in the emission and sensitivity with a micromolar detection limit.

PMID- 29167854
TI  - Nitrate-assisted photocatalytic efficiency of defective Eu-doped Pr(OH)3
      nanostructures.
AB  - Pr(OH)3 one-dimensional nanostructures are a less studied member of lanthanide
      hydroxide nanostructures, which recently demonstrated an excellent adsorption
      capacity for organic pollutant removal from wastewater. In this study, Pr1
      xEux(OH)3 (x = 0, 0.01, 0.03, and 0.05) defective nanostructures were synthesized
      by a facile and scalable microwave-assisted hydrothermal method using KOH as an
      alkaline metal precursor. The phase and surface composition, morphology,
      vibrational, electronic and optical properties of the as-prepared samples were
      characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS),
      inductively coupled plasma optical emission spectrometry (ICP-OES), transmission
      electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM),
      Raman, infrared (IR), photoluminescence (PL), and diffuse reflectance
      spectroscopy (DRS). It was deduced that the incorporation of Eu3+ ions promoted
      the formation of oxygen vacancies in the already defective Pr(OH)3, subsequently
      changing the Pr(OH)3 nanorod morphology. The presence of KNO3 phase was
      registered in the Eu-doped samples. The oxygen-deficient Eu-doped Pr(OH)3
      nanostructures displayed an improved photocatalytic activity in the removal of
      reactive orange (RO16) dye under UV-vis light irradiation. An enhanced
      photocatalytic activity of the Eu-doped Pr(OH)3 nanostructures was caused by the
      synergetic effect of oxygen vacancies and Eu3+ (NO3-) ions present on the Pr(OH)3
      surface, the charge separation efficiency and the formation of the reactive
      radicals. In addition, the 3% Eu-doped sample exhibited very good adsorptive
      properties due to different morphology and higher electrostatic attraction with
      the anionic dye. Pr1-xEux(OH)3 nanostructures with the possibility of tuning
      their adsorption/photocatalytic properties present a great potential for
      wastewater treatment.

PMID- 29167857
TI  - Vesicle to micelle transition in the ternary mixture of L121/SDS/D2O: NMR, EPR
      and SANS studies.
AB  - Subtle changes in the microstructure and dynamics of the triblock copolymer L121,
      (ethylene oxide)5 (propylene oxide)68 (ethylene oxide)5i.e., E5P68E5, and sodium
      dodecylsulfate (SDS) system in aqueous medium were investigated using high
      resolution nuclear magnetic resonance (NMR), electron paramagnetic resonance
      (EPR) and small-angle neutron scattering (SANS) methods. NMR self-diffusion
      measurements helped us to understand the nature of binding of SDS with L121, and
      the formation of their mixed aggregates. These results showed that even at low
      [SDS] (~2 mM), the addition of L121 stabilized the dynamics of SDS. Furthermore,
      the increase in [SDS] resulted in progressive changes in the diffusion behavior
      of both SDS and L121. 13C chemical shift analysis revealed that preferential
      binding of L121 occurred on the SDS micelle surface. Deuterium (2H) NMR spin
      relaxation data evidenced that the formed mixed aggregates were non-spherical in
      terms of relaxation rate changes, and slowed the dynamics. The rotational
      correlation times of mixed aggregates were estimated from EPR analysis. A SANS
      study indicated the presence of uni- and multi-lamellar vesicles of L121 at low
      [SDS]. The vesicles transformed to mixed L121-SDS micelles in the presence of a
      higher [SDS]. This was supported by the measurements of 2H NMR spin-relaxation
      and EPR rotational correlation times.

PMID- 29167858
TI  - Cutaneous Squamous Cell Carcinomas in Solid Organ Transplant Recipients Compared
      With Immunocompetent Patients.
AB  - Importance: Solid organ transplant recipients (SOTRs) have a 100-fold increased
      risk of squamous cell carcinoma (SCC), and they may develop more aggressive SCCs
      compared with immunocompetent individuals. Objective: To compare outcomes
      associated with aggressive behavior of SCC in SOTRs and high-risk immunocompetent
      patients. Design, Setting, and Participants: A retrospective cohort study of 58
      SOTRs and 40 immunocompetent patients evaluated at the Yale Transplant
      Dermatology Clinic in New Haven, Connecticut, who had at least 1 SCC confirmed
      histopathologically between January 1, 2008, and December 31, 2015. Cumulative
      follow-up time for this study was 369 patient-years. Exposure: Immunosuppressive
      medication regimen for SOTRs. Main Outcomes and Measures: The primary outcome
      measure was tumor depth of SCC. Secondary outcome measures that reflected tumor
      aggressiveness included perineural invasion, regional metastases, nodal
      metastases, disease-specific death, and overall death. Results: Of the 58 SOTR
      study participants, 14 were women and 44 were men; the mean (SD) age was 61.3
      (8.4) years. Of the 40 immunocompetent study participants, 16 were women and 24
      were men; the mean (SD) age was 69.8 (10.9) years, resulting in a statistically
      significant difference from the SOTR group. The mean (SD) number of years that
      SOTRs were immunosuppressed was 14.6 (9.2) years (range, 2-37 years). The SOTR
      and immunocompetent groups were statistically comparable regarding race and sex,
      patient care, follow-up time, numbers of skin lesions, and field cancerization
      and chemopreventive therapies. The SOTR group had a significantly higher annual
      frequency of visits (mean [SD], 4 [2] vs 3 [2] office visits per patient per
      year, P = .02) and annual biopsy rates (mean [SD], 6 [4] vs 5 [3] biopsies per
      patient per year, P = .04). The SOTRs developed SCCs that did not appear to be
      significantly more aggressive than those found in the immunocompetent control
      group. These SOTRs also did not develop significantly thicker tumors than the
      immunocompetent control group (median [IQR] tumor depth, 1.30 [0.90-1.60] mm in
      35 SOTRs vs 1.22 [1.10-1.60] mm in 20 immunocompetent patients). Conclusions and
      Relevance: The increased risk and the potential for aggressive behavior of SCCs
      in SOTRs may be successfully managed at a level comparable to that in high-risk
      immunocompetent individuals through close adherence to current dermatologic
      surveillance recommendations and a marginally lower threshold for biopsy of
      suspicious lesions for SOTRs.

PMID- 29167859
TI  - Challenges, Perceptions, and Readiness of Oncology Clinicians for the MACRA
      Quality Payment Program.

PMID- 29167860
TI  - Incident Cancer in Cancer Survivors-When Cancer Lurks in the Background.

PMID- 29167861
TI  - Ultrasonographic-Guided Resuscitation of the Surgical Patient.

PMID- 29167862
TI  - Coronary Computed Tomography-Based Fractional Flow Reserve-Reply.

PMID- 29167863
TI  - Association of Parathyroid Hormone Level With Postthyroidectomy Hypocalcemia: A
      Systematic Review.
AB  - Importance: There has been an increased interest in measuring parathyroid hormone
      (PTH) levels as an early predictive marker for the development of hypocalcemia
      after total thyroidectomy. However, significant variation exists in the timing,
      type of assay, and thresholds of PTH in the literature. Objective: We performed a
      systematic review to examine the utility of PTH levels in predicting temporary
      postthyroidectomy hypocalcemia. Evidence Review: A systematic literature review
      of studies published prior to May 25, 2016 was performed within PubMed, EMBASE,
      SCOPUS, and Cochrane databases using the following terms and keywords:
      "thyroidectomy," "parathyroid hormone," and "hypocalcaemia," "calcium," or
      "calcitriol." Each candidate full-text publication was reviewed by 2 independent
      reviewers and selected for data extraction if the study examined the prognostic
      significance of PTH obtained within 24 hours after thyroidectomy to predict
      hypocalcaemia. Studies were excluded if calcium supplementation was used
      routinely or based on a PTH level. Study characteristics, PTH parameters used to
      predict hypocalcemia, and their respective accuracies were summarized. Findings:
      The initial search yielded 2417 abstracts. Sixty-nine studies, comprising 9163
      patients, were included. Overall, for an absolute PTH threshold, the median
      accuracy, sensitivity, and specificity were 86%, 85%, and 86%, respectively. For
      a percentage change over time the median accuracy, sensitivity, and specificity
      were 89%, 88%, and 90%, respectively. Conclusions and Relevance: The existing
      literature regarding PTH levels to predict postthyroidectomy hypocalcemia is
      extremely heterogeneous. A single PTH threshold is not a reliable measure of
      hypocalcemia. Additional prospective studies controlled for timing of laboratory
      draws and a priori defined PTH thresholds need to be performed to ascertain the
      true prognostic significance of PTH in predicting postthyroidectomy
      hypocalcaemia.

PMID- 29167864
TI  - Hybrid Cartilage-Modifying Otoplasty Technique and Outcomes.
AB  - Importance: Otoplasty is performed to correct prominauris, one of the most common
      head and neck congenital deformities. Advances in combination hybrid approaches
      enable surgeons to achieve greater precision and accuracy. Objective: To describe
      a hybrid cartilage-modifying approach and evaluate the procedure's effectiveness
      and safety. Design, Setting, and Participants: Medical record review including
      patients undergoing otoplasty by the present technique from January 2006 to
      December 2016 as performed by the senior author at a tertiary academic referral
      center. Twenty-three patients underwent 24 total procedures including both
      bilateral (n = 17) and unilateral (n = 7) procedures. Two procedures were
      revisions. Interventions: Hybrid cartilage-modifying otoplasty procedure. Main
      Outcomes and Measures: Preoperative and postoperative measurements were recorded.
      Paired sample t testing was performed to assess changes between preoperative
      superior, middle, and inferior helical measurements and corresponding
      postoperative measurements for all operated ears. Two-tailed, independent sample
      t testing was performed to compare postoperative differences between right and
      left ears within separate superior, middle, and inferior measurements in patients
      undergoing bilateral otoplasty. Results: Twenty-four surgeries were performed on
      23 patients. The mean (SD) age at surgery was 16.3 (13.6) years with 13 patients
      (58%) between the ages of 4 and 10 years. Preoperatively, the mean (SD) superior,
      middle, and inferior helical rim-to-mastoid distance of the 41 discrete ears
      measured 16.5 (3.1) mm, 24.1 (3.8) mm, and 19.3 (4.4) mm, respectively. Mean (SD)
      postoperative measurements were 12.1 (2.4) mm, 14.7 (2.5) mm, and 14.0 (2.8) mm,
      respectively, for mean (SD) decreases of 4.4 (2.7) mm, 9.4 (3.4) mm, and 5.3
      (3.6) mm. For the 17 bilateral procedures, the mean (standard error)
      postoperative scores between ears measured 0.7 (0.9) mm for the superior, 0.5
      (0.9) mm for the middle, and 0.2 (1.0) mm for the inferior. The unaffected ear
      was measured in 4 of 7 (57%) of patients undergoing unilateral otoplasty, and the
      mean (SD) postoperative differences between left and right ears were 1.3 (0.8)
      mm, 3.0 (1.2) mm, and 1.0 (0.7) mm for the superior, middle, and inferior,
      respectively. Preoperative-to-postoperative differences for all ears (n = 41)
      were significant (P < .001 for all) for superior, middle, and inferior
      measurements. There were no significant absolute differences identified for
      superior (P = .41), middle (P = .58), and inferior (P = .88) measurements
      regarding left vs right postoperative comparisons for bilateral otoplasties. One
      patient undergoing bilateral repair required subsequent revision surgery of 1
      ear. Two patients developed chronic suture site irritation, and 1 patient
      developed a hematoma. Conclusions and Relevance: The present technique allows
      multiple opportunities to adjust the auricular parameters. The results indicate a
      low revision rate and high degree of symmetry. Level of Evidence: 4.

PMID- 29167865
TI  - The Hospital Readmissions Reduction Program-Targeting Weaknesses and Finding the
      Readmission Floor.

PMID- 29167866
TI  - Prevalence of Prior Cancer Among Persons Newly Diagnosed With Cancer: An Initial
      Report From the Surveillance, Epidemiology, and End Results Program.
AB  - Importance: The US cancer survivor population is rapidly growing. Cancer
      survivors are frequently excluded from cancer clinical trials and observational
      research. Objective: To examine prevalence of prior cancer among individuals
      newly diagnosed with cancer. Design, Setting, and Participants: Linked
      observations across the population-based Surveillance, Epidemiology, and End
      Results (SEER) program of cancer registries (1975-2013) for 740 990 persons newly
      diagnosed with cancer from January 2009 through December 2013. Prevalence of
      prior cancer was estimated by age (<65 years vs >=65 years) and incident cancer
      type. Main Outcomes and Measures: Prevalence of prior cancer was derived from
      SEER sequence numbers, which represent the order of all primary reportable tumors
      diagnosed in a lifetime. Incident cancers were categorized as: (1) first or only
      primary; (2) second order or higher primary in the same cancer site; and (3)
      second order or higher primary in a different cancer site. Results: Of 765 843
      incident cancers diagnosed between 2009 and 2013, 141 021 (18.4%) represented a
      second order or higher primary cancer. Overall, approximately one-fourth (25.2%)
      of older (>=65 years) and 11% of younger adults newly diagnosed with cancer had a
      history of prior cancer. Prevalence of prior cancer ranged from 3.5% to 36.9%
      according to incident cancer type and age, with most prior cancers diagnosed in a
      different cancer site. Conclusions and Relevance: A substantial proportion of
      patients diagnosed with incident cancer in the United States have survived a
      prior cancer. These patients may be excluded from clinical trials and
      underrepresented in observational research, and little is known about their
      treatment and survivorship needs. Understanding the nature and impact of prior
      cancer is critical to improving clinical trial accrual and generalizability,
      disease outcomes, and patient experience.

PMID- 29167868
TI  - Efficacy and Safety of Titanium Miniplates for Patients Undergoing
      Septorhinoplasty.

PMID- 29167867
TI  - Geographic Distribution of Nonphysician Clinicians Who Independently Billed
      Medicare for Common Dermatologic Services in 2014.
AB  - Importance: Nurse practitioners (NPs) and physician assistants (PAs) are
      nonphysician clinicians (NPCs) who can deliver dermatology services. Many of
      these services are provided independently. Little is known about the types of
      services provided or where NPCs provide independent care. Objective: To examine
      characteristics of dermatology care for Medicare enrollees billed independently
      by NPCs. Design, Setting, and Participants: Retrospective review of the 2014
      Medicare Provider Utilization and Payment Data: Physician and Other Supplier
      Public Use File, which reflects fee-for-service payments to clinicians for
      services rendered to Medicare beneficiaries. Clinician location was matched with
      county-level demographic data from the American Community Survey, US Census
      Bureau. Clinicians identified using National Provider Identifier as NPs or PAs
      with at least 11 claims for common dermatology-associated Healthcare Common
      Procedure Coding System procedure codes were included. Main Outcomes and
      Measures: Total services provided by service type category, density of
      dermatologists and nondermatologists who perform dermatology-related services,
      and geographic location by county. Results: Among the cohort of NPCs were 824 NPs
      (770 [93.5%] female) and 2083 PAs (1602 [76.9%] female) who independently billed
      Medicare $59 438 802 and $171 645 943, respectively. Dermatologists were
      affiliated with 2667 (92%) independently billing NPCs. Most payments were for non
      evaluation and management services including destruction of premalignant lesions,
      biopsies, excisions of skin cancer, surgical repairs, flaps/grafts, and
      interpretation of pathologic analysis. Nurse practitioners and PAs billed for a
      similar distribution of service categories overall. A total of 2062 (70.9%) NPCs
      practiced in counties with dermatologist density of greater than 4 per 100 000
      population. Only 3.0% (86) of independently billing NPCs practiced in counties
      without a dermatologist. Both dermatologists and NPCs were less likely to be in
      rural counties than in urban counties. Conclusions and Relevance: Nonphysician
      clinicians independently billed for a wide variety of complex dermatologic
      procedures. Most independently billing NPCs practice in counties with higher
      dermatologist densities, and nearly all these NPCs were affiliated with
      dermatologists. Further study of NPC training and integration with the
      dermatology discipline is an important part of addressing the changing US
      dermatology workforce.

PMID- 29167869
TI  - Reticular Hyperpigmented Eruption in a Young Woman.

PMID- 29167871
TI  - Hair Repigmentation With Anti-PD-1 and Anti-PD-L1 Immunotherapy: A Novel
      Hypothesis.

PMID- 29167870
TI  - Association of the Hospital Readmissions Reduction Program With Surgical
      Readmissions.

PMID- 29167872
TI  - Hair Repigmentation With Anti-PD-1 and Anti-PD-L1 Immunotherapy: A Novel
      Hypothesis-Reply.

PMID- 29167873
TI  - Open Access Information Added.

PMID- 29167874
TI  - Hair Repigmentation With Anti-PD-1 and Anti-PD-L1 Immunotherapy: A Novel
      Hypothesis.

PMID- 29167875
TI  - Treatment of CD30-Negative Refractory Mycosis Fungoides With Brentuximab Vedotin.

PMID- 29167876
TI  - Branch Duct Intraductal Papillary Mucinous Neoplasms: How Worried Should We Be
      About Worrisome Features?

PMID- 29167878
TI  - Coherence Through Incongruence-Can Genetic Markers Inform Nosology After All?

PMID- 29167877
TI  - Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in
      Psychotic Disorders: A Randomized Clinical Trial.
AB  - Importance: Despite strong theoretical rationale and preclinical evidence,
      several glutamate-targeted treatments for schizophrenia have failed in recent
      pivotal trials, prompting questions as to target validity, compound inadequacy,
      or lack of target engagement. A key limitation for glutamate-based treatment
      development is the lack of functional target-engagement biomarkers for
      translation between preclinical and early-stage clinical studies. We evaluated
      the utility of 3 potential biomarkers-ketamine-evoked changes in the functional
      magnetic imaging (fMRI) blood oxygen level-dependent response (pharmacoBOLD),
      glutamate proton magnetic resonance spectroscopy (1H MRS), and task-based fMRI
      for detecting ketamine-related alterations in brain glutamate. Objective: To
      identify measures with sufficient effect size and cross-site reliability to serve
      as glutamatergic target engagement biomarkers within early-phase clinical
      studies. Design, Setting, and Participants: This randomized clinical trial was
      conducted at an academic research institution between May 2014 and October 2015
      as part of the National Institute of Mental Health-funded Fast-Fail Trial for
      Psychotic Spectrum Disorders project. All raters were blinded to study group.
      Healthy volunteers aged 18 to 55 years of either sex and free of significant
      medical or psychiatric history were recruited from 3 sites. Data were analyzed
      between November 2015 and December 2016. Interventions: Volunteers received
      either sequential ketamine (0.23 mg/kg infusion over 1 minute followed by 0.58
      mg/kg/h infusion over 30 minutes and then 0.29 mg/kg/h infusion over 29 minutes)
      or placebo infusions. Main Outcomes and Measures: Ketamine-induced changes in
      pharmacoBOLD, 1H MRS, and task-based fMRI measures, along with symptom ratings.
      Measures were prespecified prior to data collection. Results: Of the 65
      volunteers, 41 (63%) were male, and the mean (SD) age was 31.1 (9.6) years; 59
      (91%) had at least 1 valid scan. A total of 53 volunteers (82%) completed both
      ketamine infusions. In pharmacoBOLD, a highly robust increase (Cohen d = 5.4; P <
      .001) in fMRI response was observed, with a consistent response across sites. A
      smaller but significant signal (Cohen d = 0.64; P = .04) was also observed in 1H
      MRS-determined levels of glutamate+glutamine immediately following ketamine
      infusion. By contrast, no significant differences in task-activated fMRI
      responses were found between groups. Conclusions and Relevance: These findings
      demonstrate robust effects of ketamine on pharmacoBOLD across sites, supporting
      its utility for definitive assessment of functional target engagement. Other
      measures, while sensitive to ketamine effects, were not sufficiently robust for
      use as cross-site target engagement measures. Trial Registration:
      clinicaltrials.gov Identifier: NCT02134951.

PMID- 29167879
TI  - Racial Differences in Plasma Levels of N-Terminal Pro-B-Type Natriuretic Peptide
      and Outcomes: The Reasons for Geographic and Racial Differences in Stroke
      (REGARDS) Study.
AB  - Importance: Recent studies have suggested that the natriuretic peptide system may
      be endogenously suppressed in black individuals who are free of prevalent
      cardiovascular disease. Whether natriuretic peptide levels contribute to racial
      disparities in clinical outcomes is unknown. Objective: To examine racial
      differences in N-terminal pro-B-type natriuretic peptide (NTproBNP) levels and
      their association with all-cause mortality and cause-specific mortality in the
      Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Design,
      Setting, and Participants: Baseline NTproBNP levels were measured in a randomly
      selected sample of 4415 REGARDS study participants. Those with prevalent
      cardiovascular disease and renal dysfunction were excluded. From July 1, 2003, to
      September 12, 2007, among the remaining 1998 individuals, racial differences in
      NTproBNP levels were estimated, and the percentage difference in NTproBNP levels
      by race was meta-analyzed and compared with published results on participants
      free of prevalent cardiovascular disease from the Dallas Heart Study and
      Atherosclerosis Risk in Communities study, using random effects modeling. The
      association of NTproBNP levels, race, all-cause mortality, and cause-specific
      mortality in the REGARDS study was studied using appropriate modeling techniques.
      Data analysis was conducted from July 1, 2003, to March 31, 2016. Main Outcomes
      and Measures: Racial differences in NTproBNP levels and association with all
      cause mortality and cause-specific mortality. Results: Among the 1998
      participants studied (972 women and 1026 men; median age, 63 years [interquartile
      range, 54-72 years]), median NTproBNP levels in black individuals were
      significantly lower than those in white individuals (46 pg/mL [interquartile
      range, 23-91] vs 60 pg/mL [interquartile range, 33-106]; P < .001). With
      multivariable adjustment, NTproBNP levels were up to 27% lower in black
      individuals as compared with white individuals (beta, -0.32; 95% CI, -0.40 to 
      0.24; P < .001) in the REGARDS study. In meta-analysis of the 3 cohorts, NTproBNP
      levels were 35% lower in black individuals than white individuals. Among the
      REGARDS study participants, for every 1-SD higher log NTproBNP, there was a 31%
      increased risk of death in the multivariable-adjusted model (hazard ratio, 1.31;
      95% CI, 1.11-1.54). This increase was driven primarily by association of NTproBNP
      with cardiovascular mortality (hazard ratio, 1.69; 95% CI, 1.19-2.41). No
      interaction between race and NTproBNP levels was observed with all-cause
      mortality and cause-specific mortality. Conclusions and Relevance: Plasma
      NTproBNP levels are significantly lower in black individuals as compared with
      white individuals in the REGARDS study and in pooled results from the REGARDS
      study, Dallas Heart Study, and Atherosclerosis Risk in Communities study. Higher
      NTproBNP levels were associated with higher incidence of all-cause mortality and
      cardiovascular mortality in healthy black and white individuals, and this
      association did not differ by race.

PMID- 29167881
TI  - Coronary Computed Tomography-Based Fractional Flow Reserve: A Rapidly Developing
      Field.

PMID- 29167882
TI  - Overall Survival vs Disease-Specific Survival.

PMID- 29167880
TI  - Association Between Schizophrenia-Related Polygenic Liability and the Occurrence
      and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder.
AB  - Importance: Bipolar disorder (BD) overlaps schizophrenia in its clinical
      presentation and genetic liability. Alternative approaches to patient
      stratification beyond current diagnostic categories are needed to understand the
      underlying disease processes and mechanisms. Objective: To investigate the
      association between common-variant liability for schizophrenia, indexed by
      polygenic risk scores (PRSs), and psychotic presentations of BD. Design, Setting,
      and Participants: This case-control study in the United Kingdom used multinomial
      logistic regression to estimate differential PRS associations across categories
      of cases and controls. Participants included in the final analyses were 4436
      cases of BD from the Bipolar Disorder Research Network. These cases were compared
      with the genotypic data for 4976 cases of schizophrenia and 9012 controls from
      the Type 1 Diabetes Genetics Consortium study and the Generation Scotland study.
      Data were collected between January 1, 2000, and December 31, 2013. Data analysis
      was conducted from March 1, 2016, to February 28, 2017. Exposures: Standardized
      PRSs, calculated using alleles with an association threshold of P < .05 in the
      second Psychiatric Genomics Consortium genome-wide association study of
      schizophrenia, were adjusted for the first 10 population principal components and
      genotyping platforms. Main Outcomes and Measures: Multinomial logit models
      estimated PRS associations with BD stratified by Research Diagnostic Criteria
      subtypes of BD, by lifetime occurrence of psychosis, and by lifetime mood
      incongruent psychotic features. Ordinal logistic regression examined PRS
      associations across levels of mood incongruence. Ratings were derived from the
      Schedules for Clinical Assessment in Neuropsychiatry interview and the Bipolar
      Affective Disorder Dimension Scale. Results: Of the 4436 cases of BD, 2966 (67%)
      were female patients, and the mean (SD) age at interview was 46 [12] years.
      Across clinical phenotypes, there was an exposure-response gradient, with the
      strongest PRS association for schizophrenia (risk ratio [RR] = 1.94; 95% CI, 1.86
      2.01), followed by schizoaffective BD (RR = 1.37; 95% CI, 1.22-1.54), bipolar I
      disorder subtype (RR = 1.30; 95% CI, 1.24-1.36), and bipolar II disorder subtype
      (RR = 1.04; 95% CI, 0.97-1.11). Within BD cases, there was an effect gradient,
      indexed by the nature of psychosis. Prominent mood-incongruent psychotic features
      had the strongest association (RR = 1.46; 95% CI, 1.36-1.57), followed by mood
      congruent psychosis (RR = 1.24; 95% CI, 1.17-1.33) and BD with no history of
      psychosis (RR = 1.09; 95% CI, 1.04-1.15). Conclusions and Relevance: For the
      first time to date, a study shows a polygenic-risk gradient across schizophrenia
      and BD, indexed by the occurrence and level of mood-incongruent psychotic
      symptoms.

PMID- 29167883
TI  - Overall Survival vs Disease-Specific Survival-Reply.

PMID- 29167884
TI  - Paving the Way for Targeted Drug Development in Schizophrenia.

PMID- 29167885
TI  - Lymphatic Mapping and Sentinel Lymph Node Biopsy for Breast Cancer.

PMID- 29167886
TI  - Payment Reform to Enhance Collaboration of Primary Care and Cardiology: A Review.
AB  - Importance: The US health care system faces an unsustainable trajectory of high
      costs and inconsistent outcomes. The fee-for-service payment model has
      contributed to inefficiency, and new payment methods are a promising approach to
      improving value. Health reforms are needed to increase patient access, reduce
      costs, and improve health care quality, and the landmark Medicare Access and CHIP
      Reauthorization Act presents a roadmap for reform. The product of a collaboration
      between primary care and cardiology clinicians, this review describes a
      conceptual approach to delivery and payment reforms that aim to better support
      primary care-cardiology comanagement of chronic cardiovascular disease (CVD).
      Observations: Few existing alternative payment models specifically address long
      term management of CVD. Primary care medical homes and accountable care
      organizations come closest, but both emphasize primary care, and cardiologists
      have often not been well engaged. A collaborative care framework should
      articulate distinct roles and responsibilities for primary care and cardiology in
      CVD comanagement. Finally, a series of payment models aim to better support
      clinicians in providing accountable, seamless, and patient-centered cardiac care.
      Conclusions & Relevance: Clinical leadership is essential during this time of
      change in the health care system. Patients often struggle to navigate a
      fragmented and expensive system, whereas clinicians often practice with
      incomplete information about tests, treatments, and recommendations by their
      colleagues. The payment models described in this review offer an opportunity to
      create more satisfying approaches to patient care while improving value. These
      models have potential to support more effective coordination and to facilitate
      broader health care system transformation.

PMID- 29167887
TI  - Addressing the Causality Gap in Human Psychiatric Neuroscience.

PMID- 29167888
TI  - White Retinal Lesions in a Patient With Leukemia.

PMID- 29167889
TI  - Revision Surgery After Dacryocystorhinostomy in a National Cohort.

PMID- 29167890
TI  - Considerations When Temporal Order Is Not Clear.

PMID- 29167891
TI  - The Promise and Challenges of CAR-T Gene Therapy.

PMID- 29167893
TI  - Worsening Respiratory Distress in a 7-Month-Old Infant.

PMID- 29167892
TI  - Association of Prognostic Value of Primary Tumor Location in Stage III Colon
      Cancer With RAS and BRAF Mutational Status.
AB  - Importance: We know of no data on the prognostic value of primary tumor location
      (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in
      patients who have undergone resection for colon cancer (CC) and have been treated
      with current standard adjuvant chemotherapy. Objective: To determine the
      prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in
      patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid
      [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab.
      Design, Setting, and Participants: This post hoc analysis included patients with
      available tumor blocks of resected stage III colon adenocarcinoma who
      participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8
      phase 3 randomized trial. Among the 2559 patients who underwent randomization,
      1900 were screened by next-generation sequencing, which showed that 1869 had full
      information concerning PTL. We categorized primary tumor site as located proximal
      (right) or distal (left) to the splenic flexure. Main Outcomes and Measures: The
      associations between PTL (right- vs left-sided) and disease-free survival (DFS),
      survival after relapse (SAR), and overall survival (OS) were assessed by Cox
      models and adjusted for clinical and pathological features, treatment, and MSI,
      BRAF, and RAS status. Results: Among the 1869 patients (1056 [57%] male; mean
      [SD] age, 59.4 [9.5] years) with full molecular data analyzed, 755 (40%) had a
      right-sided tumor, 164 (10%) had MSI, 942 (50%) had RAS mutations, and 212 (11%)
      had BRAF mutations. Right-sided tumor location was not prognostic for DFS in the
      whole population but was associated with a shorter SAR (hazard ratio [HR], 1.54;
      95% CI, 1.23-1.93; P = .001) and OS (HR, 1.25; 95% CI, 1.02-1.54; P = .03). When
      looking at DFS in the different molecular subgroups, we found similar results for
      microsatellite-stable tumors and tumors with MSI; a better DFS in right-sided vs
      left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P
      = .046); and a worse DFS in right-sided vs left-sided tumors in patients with RAS
      and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04). These results
      were found independently of the treatment received, and no beneficial effect of
      cetuximab on DFS or OS was observed in left-sided tumors. Conclusions and
      Relevance: Although right-sided tumor location is associated with poor survival
      in patients with metastatic CC as previously reported, the association with
      disease recurrence appears to vary for patients with stage III CC and RAS or BRAF
      mutations vs those with double wild type.

PMID- 29167894
TI  - Can Exercise Prevent Knee Osteoarthritis?

PMID- 29167895
TI  - Personalized Medicine and the Contradictions and Limits of First-Generation
      Deescalation Trials in Patients With Human Papillomavirus-Positive Oropharyngeal
      Cancer.

PMID- 29167896
TI  - Association of Abnormal Renal Profiles and Proliferative Diabetic Retinopathy and
      Diabetic Macular Edema in an Asian Population With Type 2 Diabetes.
AB  - Importance: The comorbidity of chronic kidney disease and diabetic retinopathy
      (DR) is well known. However, to our knowledge, no cohort study has demonstrated
      the effect of chronic kidney disease on the development or progression of DR.
      Objective: To investigate the association of chronic kidney disease with the
      development of DR and diabetic macular edema (DME) in type 2 diabetes. Design,
      Setting, and Participants: This 8-year prospective cohort study that was
      conducted in 2 medical centers in Taiwan included 2135 patients with type 2
      diabetes. Exposures: The baseline and mean follow-up renal profiles including
      serum creatinine level, estimated glomerular filtration rate (eGFR), and urinary
      albumin/creatinine ratio (ACR). Main Outcomes and Measures: Diabetic retinopathy
      and DME were detected with nonmydriatic fundus photography. Cox regression
      analyses was used to evaluate the hazard ratios (HRs) for the renal profiles of
      new-onset DR, proliferative DR, and DME. Results: The mean (SD) age of the study
      participants was 63.4 (11.9) years and 1025 (48%) were women. A higher serum
      creatinine level (HR of 2.358 for an increase of 1 mg/dL [to convert to
      micromoles per liter, multiply by 76.25]; 95% CI, 1.901-2.924; P < .001), an
      estimated glomerular filtration rate of less than 60 mL/min/1.73m2 (40-60: HR,
      2.235; 95% CI, 1.351-4.035; P = .002; 30-45: HR, 2.625; 95% CI, 1.436-4.798; P =
      .002; <30: HR, 5.488; 95% CI, 2.739-10.993; P < .001), and a urinary albumin to
      creatinine ratio (ACR) of more than 30 mg/g (31-300: HR, 3.202; 95% CI, 2.029
      5.053; P < .001; >300: HR, 6.652; 95% CI, 3.922-11.285; P < .001) at baseline
      were all associated with the development of proliferative DR. A baseline urinary
      ACR of more than 30 mg/g (31-300: HR, 1.563; 95% CI, 1.078-2.267; P = .02; >300:
      HR, 2.707; 95% CI, 1.640-4.470; -2.707; P < 0.001) was associated with the
      development of DME. After adjusting the baseline values, the mean follow-up renal
      profiles, including a higher serum creatinine level (HR, 2.369 per mg/dL; 95% CI,
      1.704-3.293; P < .001), an estimated glomerular filtration rate of less than 30
      mL/min/1.73m2 (HR, 4.215; 95% CI, 1.265-14.039; P = .02), and a urinary ACR of
      more than 30 mg/g (31-300: HR, 2.344; 95% CI, 1.200-4.503; P = .01; >300: HR,
      4.193; 95% CI, 1.638-10.735; P = .003) were still correlated with new-onset PDR
      during the follow-up periods. Conclusions and Relevance: Abnormal renal profiles
      at baseline, including a high serum creatinine level, low estimated glomerular
      filtration rate, and high urinary ACR, were associated with the development of
      PDR in patients with type 2 diabetes. A high baseline urinary ACR was associated
      with DME. Abnormal mean follow-up renal profiles were still correlated with new
      onset PDR after adjusting for baseline values. Aggressive treatment for chronic
      kidney disease may have a role in preventing the deterioration of DR.

PMID- 29167897
TI  - Retinal Avascularity and Neovascularization Associated With LAMA1 (laminin1)
      Mutation in Poretti-Boltshauser Syndrome.

PMID- 29167898
TI  - Factors Associated With Failure of Adult Strabismus-20 Questionnaire Scores to
      Improve Following Strabismus Surgery.
AB  - Importance: Health-related quality of life (HRQOL) typically improves following
      strabismus surgery. Nevertheless, for some patients, HRQOL does not improve, and
      reasons for this are unknown. Objective: To identify factors associated with
      failure of adult strabismus-20 (AS-20) HRQOL scores to improve following
      strabismus surgery. Design, Setting, and Participants: Prospective observational
      case series at the Mayo Clinic, Rochester, Minnesota, comprising 276 adults,
      between July 2012 and August 2016. Main Outcomes and Measures: Participants
      completed the AS-20 HRQOL questionnaire, diplopia questionnaire, Center for
      Epidemiologic Studies Depression Scale-Revised (CESD-R) (depressive symptoms),
      and Type-D Scale 14 questionnaire (type-Distressed [type-D] personality) both
      preoperatively and 6 weeks postoperatively. To assess factors associated with
      failure of HRQOL to improve (no change or decrease in score), univariate and
      multiple logistic regression analyses were performed. Each of the 4 AS-20 domains
      (self-perception, interactions, reading function, and general function) were
      analyzed separately including only patients able to improve at least by the
      magnitude of previously defined 95% limits of agreement. Factors assessed were
      age (at onset and at surgery), sex, number of previous surgeries, presence of
      visually obtrusive facial anomaly, visual acuity, preoperative and postoperative
      diplopia questionnaire scores, alignment (as a vector), presence of esotropia,
      presence of a vertical deviation, CESD-R scores, and type-D personality. Stepwise
      multiple logistic regression analyses were performed to assess factors associated
      with failure of AS-20 scores to improve for each domain. Results: Of the 276
      participants, the median age was 57 years (range, 18-91 years), 153 were women
      (55%), and 266 were white (96%). Failure to improve was associated with worse
      diplopia postoperatively on the self-perception (adjusted risk ratio [RR], 1.01;
      95% CI, 1.00-1.02), reading function (adjusted RR, 1.02; 95% CI, 1.01-1.03), and
      general function domains (adjusted RR, 1.02; 95% CI, 1.01-1.03). In addition,
      failure to improve on the self-perception domain was associated with type-D
      personality postoperatively (adjusted RR, 4.26; 95% CI, 1.90-9.57) and failure to
      improve on the interactions domain was associated with postoperative depressive
      symptoms (adjusted RR, 1.04; 95% CI, 1.02-1.06) and coexisting visually obtrusive
      anomaly (adjusted RR, 2.12; 95% CI, 1.04-4.32). Conclusions and Relevance:
      Postoperative diplopia, depressive symptoms, type-D personality, and visually
      obtrusive facial anomalies were associated with failure of AS-20 scores to
      improve (remaining the same or worsening) following strabismus surgery. The
      association of nonstrabismus factors may have implications for patient treatment
      and is worthy of continued study.

PMID- 29167900
TI  - Natriuretic Peptide Deficiency-When There Is Too Little of a Good Thing.

PMID- 29167899
TI  - Comparative Effectiveness of Resection vs Surveillance for Pancreatic Branch Duct
      Intraductal Papillary Mucinous Neoplasms With Worrisome Features.

PMID- 29167901
TI  - Association of Neurocognitive Deficits With Radiotherapy or Chemoradiotherapy for
      Patients With Head and Neck Cancer.
AB  - Importance: Neurocognitive deficits (NCD) have been observed in noncentral
      nervous system cancers, yet short- and long-term neurocognitive data on patients
      treated for head and neck cancer (HNC) are lacking. Objective: To assess
      objective neurocognitive function before and after definitive radiation therapy
      for HNC. Design, Setting, and Participants: In a prospective, longitudinal study,
      neurocognitive function and self-reported symptoms were assessed in 80 patients
      with histologically proven HNC requiring definitive chemoradiotherapy or
      radiotherapy and in 40 healthy controls 4 times (baseline, 6, 12, and 24 months
      after baseline) prior to commencing treatment at Princess Margaret Cancer Centre,
      Toronto, Canada. Main Outcomes and Measures: Neurocognitive test scores were
      converted to age-corrected z scores (mean, 0; standard deviation, 1) and reported
      as mean scores, standardized regression-based scores, and frequencies of
      impairments in intellectual capacity, concentration, memory, executive function,
      processing speed, and motor dexterity. Multivariable analysis was used to
      identify factors associated with NCD 2 years after treatment. Results: Eighty
      patients and 40 healthy controls enrolled. Analyses revealed significant
      differences between patient and control mean performance in some domains, with
      patient deficits increasing over time: intellectual capacity (Cohen d, effect
      sizes [95% CIs] of -0.46 [-0.64 to 0.30], -0.51 [-0.72 to -0.30], and -0.70 [
      0.92 to -0.49] for time points 6, 12, and 24 months, respectively);
      concentration/short-term attention span (-0.19 [-0.37 to 0.00], -0.38 [-0.55 to 
      0.21], -0.54 [-0.71 to -0.37]); verbal memory (-0.16 [-0.33 to 0.02], -0.38 [
      0.64 to -0.12], -0.53 [-0.74 to -0.32]); executive function (-0.14 [-0.27 to
      0.00], -0.34 [-0.52 to -0.16], -0.43 [-0.64 to -0.22]), and global cognitive
      function composite (-0.38 [-0.55 to -0.22], -0.75 [-0.92 to -0.58], -1.06 [-1.26
      to -0.86]). There was an increased rate of impaired global neurocognitive
      functioning among patients (38%) at 24 months compared with controls (0%).
      Neurocognitive deficits were not associated with baseline cytokines. Conclusions
      and Relevance: Head and neck cancer survivors have neurocognitive sequelae up to
      2 years after definitive chemoradiotherapy or radiation treatment. Patients and
      health care teams should know about such potential risks. Further research is
      warranted in search of strategies to avoid, reduce, and compensate for declines.

PMID- 29167902
TI  - Trends in Use of Ambulatory Surgery Centers for Cataract Surgery in the United
      States, 2001-2014.
AB  - Importance: Cataract surgery is commonly performed at ambulatory surgery centers
      (ASCs) and hospital outpatient departments (HOPDs). These venues differ in many
      ways, including surgical efficiency, patient throughput, patient safety, and
      costs per surgery. Objective: To determine trends in use of ASCs and HOPDs for
      cataract surgery from 2001 to 2014 and factors affecting the site of surgery.
      Design, Setting, and Participants: This retrospective longitudinal cohort
      analysis involved individuals 40 years and older who underwent cataract surgery
      between January 2001 and December 2014 from a nationwide US managed care network.
      Data were analyzed from February 2016 to February 2017. Main Outcomes and
      Measures: We identified all enrollees who underwent cataract surgery and
      determined whether the surgery was performed at an ASC or HOPD. We calculated the
      proportion of surgeries performed at each site each year from 2001 to 2014.
      Multivariable logistic regression identified characteristics of enrollees who had
      cataract surgery at an ASC vs a HOPD. We also assessed geographic variation in
      the proportion of cataract surgeries performed at ASCs in 306 communities
      throughout the United States. Results: Of the 369 320 enrollees included in this
      study, 208 319 (56.4%) were female, and the mean (SD) age was 66.3 (10.4) years.
      All enrollees underwent cataract surgery (531 325 surgeries) from 2001 to 2014.
      Of these, 237 046 (64.2%) underwent cataract surgery at an ASC. The proportion of
      cataract surgeries performed at ASCs increased from 43.6% in 2001 to 73.0% in
      2014. Compared with enrollees with incomes less than $40 000, those with incomes
      greater than $100 000 were 20% more likely to undergo cataract surgery at an ASC
      (odds ratio, 1.20; 95% CI, 1.12-1.29). Enrollees with better overall health were
      no more likely to undergo cataract surgery at an ASC (odds ratio, 1.00; 95% CI,
      0.99-1.00) than at an HOPD. Enrollees who lived in communities without
      certificate of need laws were more than twice as likely to have surgery at an ASC
      (odds ratio, 2.49; 95% CI, 2.35-2.63). The proportion of cataract surgeries
      performed at ASCs from 2012 to 2014 varied considerably, from 1.6% in La Crosse,
      Wisconsin, to 98.8% in Pueblo, Colorado. Conclusions and Relevance: We observed a
      large shift in the site of cataract surgery from HOPDs to ASCs from 2001 to 2014.
      Future research is needed to assess the effect of this transition in site of
      surgical care on patient access to surgery, surgical outcomes, patient safety,
      and societal costs.

PMID- 29167903
TI  - Access to Ophthalmologists in States Where Optometrists Have Expanded Scope of
      Practice.
AB  - Importance: As the United States considers how to best structure its health care
      services, specialty care availability is receiving increased focus. This study
      assesses whether patients lack reasonable access to ophthalmologists in states
      where optometrists have been granted expanded scope of practice. Objective: To
      determine the estimated travel time (ETT) to the nearest ophthalmologist office
      for persons residing in states that have expanded scope of practice for
      optometrists, and to quantify ETT to the nearest ophthalmologist for Medicare
      beneficiaries who received surgical care from optometrists in those states
      between 2008 and 2014. Design, Setting, and Participants: This study used data
      from the 2010 US census, a 2016 American Academy of Ophthalmology member
      database, and a data set of claims data for a random sample of 20% of
      beneficiaries enrolled in Medicare nationwide from 2008 to 2014 (n=14 063 725).
      Combining these sources with geographic information systems analysis, the ETT to
      the nearest ophthalmologist office was calculated for every resident of Kentucky,
      Oklahoma, and New Mexico. This study also assessed ETT to the nearest
      ophthalmologist for Medicare beneficiaries in those states who had received
      surgery from an optometrist from 2008 to 2014. Data analyses were conducted from
      July 2016 to July 2017. Main Outcomes and Measures: The proportion of residents
      of Kentucky, Oklahoma, and New Mexico who live within an ETT of 10, 30, 45, 60,
      or 90 minutes of the nearest ophthalmologist office. Results: The study included
      4 339 367 Kentucky residents, 3 751 351 Oklahoma residents, and 2 059 179 New
      Mexico residents. Of these, 5 140 547 (50.6%) were female. Racial/ethnic
      composition included 7 154 847 people (70.5%) who were white, 640 608 (6.3%) who
      were black, and 1 418 246 (14.0%) who were Hispanic. The mean (SD) age was 37.8
      (22.8) years. More than 75% of residents in the 3 states lived within an ETT of
      30 minutes to the nearest ophthalmology office, and 94% to 99% of residents lived
      within an ETT of 60 minutes to the nearest ophthalmology office. Among Medicare
      beneficiaries who received surgery by optometrists, 58.3%, 51.1%, and 46.9% in
      Kentucky, Oklahoma, and New Mexico, respectively, lived within an ETT of 30
      minutes from the nearest ophthalmologist office. Conclusions and Relevance: In
      the states where optometrists have expanded scope of practice, most residents
      lived within an ETT of 30 minutes of the nearest ophthalmologist office, as do
      half of Medicare beneficiaries who received surgical care from optometrists.
      These results can help inform policy makers when weighing the pros and cons of
      scope of practice expansion for optometrists.

PMID- 29167904
TI  - Prevalence, Characteristics, and Treatment Patterns of Hearing Difficulty in the
      United States.
AB  - Importance: Hearing loss is one of the most prevalent chronic conditions in the
      United States and has been associated with negative physical, social, cognitive,
      economic, and emotional consequences. Despite the high prevalence of hearing
      loss, substantial gaps in the utilization of amplification options, including
      hearing aids and cochlear implants (CI), have been identified. Objective: To
      investigate the contemporary prevalence, characteristics, and patterns of
      specialty referral, evaluation, and treatment of hearing difficulty among adults
      in the United States. Design, Setting, and Participants: A cross-sectional
      analysis of responses from a nationwide clustered representative sample of adults
      who participated in the 2014 National Health Interview Survey and responded to
      the hearing module questions was carried out. Main Outcomes and Measures: Data
      regarding demographics as well as self-reported hearing status, functional
      hearing, laterality, onset, and primary cause of the hearing loss were collected.
      In addition, specific data regarding hearing-related clinician visits, hearing
      tests, referrals to hearing specialist, and utilization of hearing aids and CIs
      were analyzed. Results: Among 239.6 million adults, 40.3 million (16.8%)
      indicated their hearing was less than "excellent/good," ranging from "a little
      trouble hearing" to "deaf." The mean (SD) age of participants was 47 (0.2) years
      with 48.2% being men and 51.8% women. Approximately 48.8 million (20.6%) had
      visited a physician for hearing problems in the preceding 5 years. Of these,
      32.6% were referred to an otolaryngologist and 27.3% were referred to an
      audiologist. Functional hearing was reported as the ability to hear "whispering"
      or "normal voice" (225.4 million; 95.5%), to "only hear shouting" (8.0 million;
      3.4%), and "not appreciating shouting" (2.8 million; 1.1%). Among the last group,
      5.3% were recommended to have a CI, of which 22.1% had received one. Of the
      adults who indicated their hearing from "a little trouble hearing" to being
      "deaf," 12.9 million (32.2%) had never seen a clinician for hearing problems and
      11.1 million (28.0%) had never had their hearing tested. Conclusions and
      Relevance: There are considerable gaps between self-reported hearing loss and
      patients receiving medical evaluation and recommended treatments for hearing
      loss. Improved awareness regarding referrals to otolaryngologists and
      audiologists as well as auditory rehabilitative options among clinicians may
      improve hearing loss care.

PMID- 29167905
TI  - Clinics in diagnostic imaging (181). Cervical spine perineural cysts.
AB  - A 47-year-old woman who underwent resection of known spinal meningioma at the T1
      level returned for postoperative magnetic resonance imaging of the cervical
      spine. Incidentally, thin-walled structures with signal intensities that are
      similar to those of cerebrospinal fluid were found to be present in the left
      neural exit canal at the C7-T1 level and bilateral neural exit canals at the C6-7
      level. Imaging findings were in keeping with perineural cysts. Cervical spine
      perineural cysts are likely underreported, as most of them are asymptomatic. The
      imaging features and differential diagnoses of perineural cysts are discussed in
      this article.

PMID- 29167906
TI  - Ceftriaxone-induced pseudolithiasis: not just a theoretical risk.

PMID- 29167907
TI  - Definitive tests for dengue fever: when and which should I use?
AB  - Dengue is a mosquito-borne viral disease that has established itself globally in
      both endemic and epidemic transmission cycles. While diagnostic decision-making
      for dengue is often guided by clinical judgement, definitive laboratory tests,
      including rapid point-of-care tests, have many advantages in the primary care
      setting. These include providing epidemiological data and diagnostic clarity for
      atypical cases, as well as contributing to patient education and compliance. This
      article discussed the types of diagnostic methods for dengue, when to use them
      and the appropriateness of each test. Viral detection diagnostic methods such as
      NS1 antigen assays are generally used within the first week of illness onset,
      whereas dengue serology testing is most appropriate after that time frame.
      Locally available rapid point-of-care tests, which include both assays in one
      convenient test kit, can enhance dengue diagnosis in an endemic setting.

PMID- 29167908
TI  - Pilot single-centre cross-sectional study to determine emergency physicians'
      knowledge and management of sports concussion: an experience from Singapore.
AB  - INTRODUCTION: Sports concussion remains challenging to manage despite changes to
      policy and practice since the 2012 International Consensus Conference on
      Concussion in Sport. Emergency physicians (EPs) are usually the first line of
      medical care for athletes in amateur and youth collision sports. This single
      centre cross-sectional study aimed to establish EPs' understanding and management
      of concussion in Singapore. METHODS: An anonymised, 17-item online questionnaire
      was sent to EPs requesting for information on their clinical experience,
      training, exposure to concussion cases in the emergency department (ED) and
      assessed knowledge of the condition. RESULTS: Out of 65 EPs, 52 (80%) responded,
      25 (48.1%) of whom were medical officers. Over 90% had not received formal
      training in concussion management, and 73.1% regularly assessed concussion. 40
      (76.9%) EPs recognised that loss of consciousness was not essential for diagnosis
      and only 24 (46.2%) knew the most common symptom. 26 (50.0%) incorrectly reported
      that they would perform brain imaging. Among those who indicated onward referral,
      29 (55.8%) would refer concussed patients to neurosurgery. There were no
      significant differences between clinical grade or training in concussion and
      positive responses for definition, imaging modality or most common symptom of
      concussion. CONCLUSION: Concussion is a common presentation to EDs in Singapore.
      However, understanding of the condition, its clinical diagnosis, investigation
      and onward management is limited. Although EPs reported training in concussion,
      it is likely to be insufficient. Commencing relevant education programmes for
      undergraduate and postgraduate medical students may enable progressive
      acquisition of knowledge and thereby improve patient management in the future.

PMID- 29167909
TI  - Outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision
      surgery for locally advanced rectal cancer: a single-institution experience.
AB  - INTRODUCTION: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal
      excision (TME) surgery for locally advanced rectal cancer has been shown to
      improve local control and reduce toxicity, as compared to adjuvant CRT. We
      reported the outcomes of our patients with locally advanced rectal cancer treated
      at National University Hospital, Singapore. METHODS: From April 2002 to December
      2014, 117 patients with T3/4, N0/+, M0 rectal cancer received neoadjuvant CRT
      followed by TME surgery. The treatment regimen comprised a total radiotherapy
      dose of 50.4 Gy in 28 daily fractions delivered concurrently with 5-fluorouracil
      or capecitabine chemotherapy over 5.5 weeks. All patients were planned for TME
      surgery. Local control, disease-free survival, overall survival and treatment
      toxicities were analysed. RESULTS: Median follow-up was 34 (range 2-122) months.
      11.5% (13/113) of patients achieved a pathological complete response (pCR) and
      72.6% (85/117) had either tumour or nodal downstaging following neoadjuvant CRT.
      5.2% (5/96) of patients had Grade 3 acute toxicities (dermatitis and diarrhoea)
      and 3.1% (3/96) had Grade 3 late toxicities (fistula and stricture). There was no
      Grade 4 toxicity noted. The five-year local recurrence, disease-free survival and
      overall survival rates were 4.5%, 65.7% and 80.6%, respectively. Multivariate
      analysis showed that nodal positivity was a predictor of poor disease-free
      survival and poor overall survival. Tumour downstaging and pCR did not improve
      outcomes. CONCLUSION: Our outcomes were comparable to internationally published
      data, and this treatment regimen remains the standard of care for locally
      advanced rectal cancer in our local population.

PMID- 29167910
TI  - Easy-to-learn cardiopulmonary resuscitation training programme: a randomised
      controlled trial on laypeople's resuscitation performance.
AB  - INTRODUCTION: Simplifying the learning of cardiopulmonary resuscitation (CPR) is
      advocated to improve skill acquisition and retention. A simplified CPR training
      programme focusing on continuous chest compression, with a simple landmark
      tracing technique, was introduced to laypeople. The study aimed to examine the
      effectiveness of the simplified CPR training in improving lay rescuers' CPR
      performance as compared to standard CPR. METHODS: A total of 85 laypeople (aged
      21-60 years) were recruited and randomly assigned to undertake either a two-hour
      simplified or standard CPR training session. They were tested two months after
      the training on a simulated cardiac arrest scenario. Participants' performance on
      the sequence of CPR steps was observed and evaluated using a validated CPR
      algorithm checklist. The quality of chest compression and ventilation was
      assessed from the recording manikins. RESULTS: The simplified CPR group performed
      significantly better on the CPR algorithm when compared to the standard CPR group
      (p < 0.01). No significant difference was found between the groups in time taken
      to initiate CPR. However, a significantly higher number of compressions and
      proportion of adequate compressions was demonstrated by the simplified group than
      the standard group (p < 0.01). Hands-off time was significantly shorter in the
      simplified CPR group than in the standard CPR group (p < 0.001). CONCLUSION:
      Simplifying the learning of CPR by focusing on continuous chest compressions,
      with simple hand placement for chest compression, could lead to better
      acquisition and retention of CPR algorithms, and better quality of chest
      compressions than standard CPR.

PMID- 29167912
TI  - [Surgery of malignant hormone active neuroendocrine pancreatic tumors].

PMID- 29167911
TI  - Conservative treatment of hydrothorax in a patient receiving peritoneal dialysis.

PMID- 29167913
TI  - Synergistic enhancing-memory effect of donepezil and S 47445, an AMPA positive
      allosteric modulator, in middle-aged and aged mice.
AB  - Positive allosteric modulators of AMPA receptors (AMPA-PAMs) are described to
      facilitate cognitive processes in different memory-based models. Among them, S
      47445 is a novel potent and selective AMPA-PAM. In order to assess its efficacy
      after repeated administration, S 47445 effect was evaluated in two aging-induced
      memory dysfunction tasks in old mice, one short-term working memory model
      evaluated in a radial maze task and one assessing contextual memory performance.
      S 47445 was shown to improve cognition in both models sensitive to aging. In
      fact, administration of S 47445 at 0.3 mg/kg (s.c.) reversed the age-induced
      deficits of the working memory model whatever the retention interval. Moreover,
      in the contextual task, S 47445 also reversed the age-induced deficit at all
      tested doses (from 0.03 to 0.3 mg/kg, p.o.). Since donepezil, an
      acetylcholinesterase inhibitor, induces only moderate symptomatic effects on
      memory in Alzheimer's disease patients, an alternative strategy for treatment of
      cognitive symptoms could be to act simultaneously on both glutamatergic AMPA
      receptors and cholinergic pathways by combining pharmacological treatments. The
      present study further examined such effects by assessing combinations of S 47445
      and donepezil given orally during 9 days in aged C57/Bl6J mice using contextual
      memory task (CSD) and the working memory model of serial alternation task (AT).
      Interestingly, a significant synergistic memory-enhancing effect was observed
      with the combination of donepezil at 0.1 mg/kg with S 47445 at 0.1 mg/kg p.o. in
      the CSD or with S 47445 at 0.1 and 0.3 mg/kg in AT in comparison to compounds
      given alone and without any pharmacokinetic interaction.

PMID- 29167914
TI  - Reconnection to mechanical ventilation for 1 h after a successful spontaneous
      breathing trial: mortality data.

PMID- 29167915
TI  - Critical illness, disability, and the road home.

PMID- 29167916
TI  - Understanding the role of host immune responses in invasive candidiasis.

PMID- 29167917
TI  - Safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole sodium
      injections after single and multiple intravenous doses in healthy Chinese
      subjects.
AB  - PURPOSE: The objective of this study was to evaluate the safety,
      pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole (PPZ) sodium
      injections following single and multiple intravenous doses in healthy Chinese
      subjects. METHODS: The dosage groups were set as followed: 20 mg of single and
      multiple intravenous administration of S-(-)-PPZ, 40 mg of single and multiple
      intravenous administration of S-(-)-PPZ or pantoprazole, and 80 mg of single
      dosage group of S-(-)-PPZ. Subjects were sampled for pharmacokinetic analysis and
      were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after
      administration for the pharmacodynamic study. The pharmacokinetic and
      pharmacodynamic parameters were compared between S-(-)-PPZ and PPZ. Safety was
      evaluated on the basis of adverse events, vital signs, laboratory tests, and
      physical examination. RESULTS: All adverse events were mild and of limited
      duration. Maximum plasma concentration and area under the concentration-time
      curve for S-(-)-PPZ were dose proportional over the range of 20-80 mg following a
      single intravenous administration. Elimination rate constant and half-life
      observed statistical difference from a single dose to multiple doses in 40 mg of
      S-(-)-PPZ groups. After administration of a single dose, the mean 24-h
      intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg
      groups. Slightly increase of intragastric pH was found after a single dose of 40
      mg S-(-)-PPZ than 40 mg PPZ; however, the differences were not statistically
      significant. CONCLUSIONS: Twice daily of 40 mg S-(-)-PPZ sodium injections is
      effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ
      levels, most subjects presented more potent and prolonged suppression of gastric
      acid of S-(-)-PPZ, while a few subjects showed faster metabolic rate of S-(-)-PPZ
      in vivo.

PMID- 29167918
TI  - Risk factors for QTc interval prolongation.
AB  - PURPOSE: Prolongation of the QTc interval may result in Torsade de Pointes, a
      ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have
      been described, including the use of certain drugs. In clinical practice, there
      is much debate about the management of the risks involved. In this study, we
      quantified the effect of these risk factors on the length of the QTc interval.
      METHODS: We analyzed all ECGs that were taken during routine practice between
      January 2013 and October 2016 in the Spaarne Gasthuis, a general teaching
      hospital in the Netherlands. We collected laboratory values in the week before
      the ECG recording and the drugs prescribed. For the identification of risk
      factors, we used multilevel linear regression analysis to correct for multiple
      ECG recordings per patient. RESULTS: We included 133,359 ECGs in our study, taken
      in 40,037 patients. Patients using one QT-prolonging drug had a 11.08 ms (95% CI
      10.63-11.52; p < 0.001) longer QTc interval. Patients using two QT-prolonging
      drugs had a 3.04 ms (95% CI 2.06-4.02; p < 0.001) increase in the QTc interval
      compared to patients using one QT-prolonging drug. Women had a longer QTc
      interval compared to men (16.30 ms 95% CI 14.59-18.01; p < 0.001). The QTc
      interval increased with increasing age, but the difference between men and women
      diminished. Other independent risk factors that significantly prolonged the QTc
      interval with at least 10 ms were hypokalemia, hypocalcemia, and the use of loop
      diuretics. CONCLUSION: We identified and quantified various risk factors for QTc
      interval prolongation.

PMID- 29167920
TI  - ATPase activity regulation by leader peptide processing of ABC transporter
      maturation and secretion protein, NukT, for lantibiotic nukacin ISK-1.
AB  - Lantibiotic nukacin ISK-1 is produced by Staphylococcus warneri ISK-1. The dual
      functional transporter NukT, an ABC transporter maturation and secretion protein,
      contributes to cleavage of the leader peptide from the prepeptide (modified NukA)
      and the final transport of nukacin ISK-1. NukT consists of an N-terminal
      peptidase domain (PEP), a C-terminal nucleotide-binding domain (NBD), and a
      transmembrane domain (TMD). In this study, NukT and its peptidase-inactive mutant
      were expressed, purified, and reconstituted into liposomes for analysis of their
      peptidase and ATPase activities. The ATPase activity of the NBD region was shown
      to be required for the peptidase activity of the PEP region. Furthermore, we
      demonstrated for the first time that leader peptide cleavage by the PEP region
      significantly enhanced the ATPase activity of the NBD region. Taken together, the
      presented results offer new insights into the processing mechanism of lantibiotic
      transporters and the necessity of interdomain cooperation.

PMID- 29167921
TI  - Extreme widening of asymmetric giant cystic Virchow-Robin spaces.

PMID- 29167922
TI  - Correction to: Anaerobic Benzene Mineralization by Nitrate-Reducing and Sulfate
      Reducing Microbial Consortia Enriched From the Same Site: Comparison of Community
      Composition and Degradation Characteristics.
AB  - The original version of this article unfortunately contained mistakes in Table 1.
      The two data sets were accidentally missing in the table. The original article
      has been corrected.

PMID- 29167919
TI  - Propionibacterium spp.-source of propionic acid, vitamin B12, and other
      metabolites important for the industry.
AB  - Bacteria from the Propionibacterium genus consists of two principal groups:
      cutaneous and classical. Cutaneous Propionibacterium are considered primary
      pathogens to humans, whereas classical Propionibacterium are widely used in the
      food and pharmaceutical industries. Bacteria from the Propionibacterium genus are
      capable of synthesizing numerous valuable compounds with a wide industrial usage.
      Biomass of the bacteria from the Propionibacterium genus constitutes sources of
      vitamins from the B group, including B12, trehalose, and numerous bacteriocins.
      These bacteria are also capable of synthesizing organic acids such as propionic
      acid and acetic acid. Because of GRAS status and their health-promoting
      characteristics, bacteria from the Propionibacterium genus and their metabolites
      (propionic acid, vitamin B12, and trehalose) are commonly used in the cosmetic,
      pharmaceutical, food, and other industries. They are also used as additives in
      fodders for livestock. In this review, we present the major species of
      Propionibacterium and their properties and provide an overview of their functions
      and applications. This review also presents current literature concerned with the
      possibilities of using Propionibacterium spp. to obtain valuable metabolites. It
      also presents the biosynthetic pathways as well as the impact of the genetic and
      environmental factors on the efficiency of their production.

PMID- 29167923
TI  - Preoperative prediction of microvascular invasion of hepatocellular carcinoma
      using 18F-FDG PET/CT: a multicenter retrospective cohort study.
AB  - PURPOSE: The aim of this study was to assess the potential of tumor 18F
      fluorodeoxyglucose (FDG) avidity as a preoperative imaging biomarker for the
      prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC).
      METHODS: One hundred and fifty-eight patients diagnosed with Barcelona Clinic
      Liver Cancer stages 0 or A HCC (median age, 57 years; interquartile range, 50-64
      years) who underwent 18F-FDG positron emission tomography with computed
      tomography (PET/CT) before curative surgery at seven university hospitals were
      included. Tumor FDG avidity was measured by tumor-to-normal liver standardized
      uptake value ratio (TLR) of the primary tumor on FDG PET/CT imaging. Logistic
      regression analysis was performed to identify significant parameters associated
      with MVI. The predictive performance of TLR and other clinical variables was
      assessed using receiver operating characteristic (ROC) curve analysis. RESULTS:
      MVI was present in 76 of 158 patients with HCCs (48.1%). Multivariable logistic
      regression analysis revealed that TLR, serum alpha-fetoprotein (AFP) level, and
      tumor size were significantly associated with the presence of MVI (P < 0.001).
      Multinodularity was not significantly associated with MVI (P = 0.563). The area
      under the ROC curve (AUC) for predicting the presence of MVI was best with TLR
      (AUC = 0.704), followed by tumor size (AUC = 0.685) and AFP (AUC = 0.670). We
      were able to build an improved prediction model combining TLR, tumor size, and
      AFP by using multivariable logistic regression modeling (AUC = 0.756).
      CONCLUSIONS: Tumor FDG avidity measured by TLR on FDG PET/CT is a preoperative
      imaging biomarker for the prediction of MVI in patients with HCC.

PMID- 29167924
TI  - Persistent cytarabine and daunorubicin exposure after administration of novel
      liposomal formulation CPX-351: population pharmacokinetic assessment.
AB  - PURPOSE: CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin
      which has recently been FDA approved for treatment of acute myeloid leukemia
      (AML). The current study investigated the pharmacokinetics (PK) of this liposomal
      formulation. METHODS: CPX-351 PK data (cytarabine, daunorubicin, and metabolites)
      from a phase I study of relapsed and refractory AML were used for the analysis.
      Therapy was given days 1, 3, and 5 of induction (3-134 units/m2). We developed a
      population PK model to characterize CPX-351 disposition. RESULTS: 39 patients
      (3589 samples) were evaluated. Liposomal cytarabine and daunorubicin were modeled
      separately with their respective metabolites. A one-compartment model fit the
      parent compounds well; the metabolites required two-compartment models. Weight
      was an independent predictor of liposomal volumes; mild renal and liver
      dysfunction were not predictors of clearance or volume (maximum creatinine 1.6
      mg/dL and total bilirubin 1.8 mg/dL). Liposomal clearances of the two drugs were
      highly correlated and 1000-fold smaller than published non-encapsulated values
      supporting prolonged encapsulation in the liposome. CONCLUSIONS: The PK model
      demonstrates prolonged exposure to cytarabine and daunorubicin without increases
      in non-hematologic toxicity that indicates retention of the drugs within the
      liposome. The unique pharmacology of this formulation may allow for simplified
      regimens and improved outcomes.

PMID- 29167925
TI  - Why do children and adolescents bully their peers? A critical review of key
      theoretical frameworks.
AB  - Bullying is a significant public health problem for children and adolescents
      worldwide. Evidence suggests that both being bullied (bullying victimisation) and
      bullying others (bullying perpetration) are associated with concurrent and future
      mental health problems. The onset and course of bullying perpetration are
      influenced by individual as well as systemic factors. Identifying effective
      solutions to address bullying requires a fundamental understanding of why it
      occurs. Drawing from multi-disciplinary domains, this review provides a summary
      and synthesis of the key theoretical frameworks applied to understanding and
      intervening on the issue of bullying. A number of explanatory models have been
      used to elucidate the dynamics of bullying, and broadly these correspond with
      either system (e.g., social-ecological, family systems, peer-group socialisation)
      or individual-level (e.g., developmental psychopathology, genetic, resource
      control, social-cognitive) frameworks. Each theory adds a unique perspective;
      however, no single framework comprehensively explains why bullying occurs. This
      review demonstrates that the integration of theoretical perspectives achieves a
      more nuanced understanding of bullying which is necessary for strengthening
      evidence-based interventions. Future progress requires researchers to integrate
      both the systems and individual-level theoretical frameworks to further improve
      current interventions. More effective intervention across different systems as
      well as tailoring interventions to the specific needs of the individuals directly
      involved in bullying will reduce exposure to a key risk factor for mental health
      problems.

PMID- 29167926
TI  - Angiopoietin-like protein 8 in early pregnancy improves the prediction of
      gestational diabetes.
AB  - AIMS/HYPOTHESIS: Screening high-risk individuals for gestational diabetes
      mellitus (GDM) in early pregnancy conventionally relies on established maternal
      risk factors; however, the sensitivity and specificity of these factors are not
      satisfactory. The present study aimed to determine whether the concentration of
      angiopoietin-like protein 8 (ANGPTL8), either alone or combined with other risk
      factors in early pregnancy, could be used to predict subsequent GDM. METHODS:
      From August 2015 to January 2016, 474 women receiving prenatal care at around 12
      16 weeks of gestation were recruited into the study. ANGPTL8 levels were measured
      at the first prenatal visit. All the participants received a 75 g OGTT during
      weeks 24-28 of gestation. RESULTS: ANGPTL8 levels in early pregnancy were
      considerably higher in women who developed GDM than those who maintained normal
      glucose tolerance (2822 +/- 938 vs 2120 +/- 1118 pg/ml, respectively; p <
      0.0001). Multivariable logistic regression revealed that ANGPTL8 levels were
      significantly associated with risk of GDM independent of conventional risk
      factors. In addition, women in the highest quartile of ANGPTL8 concentration had
      an 8.75-fold higher risk of developing GDM compared with women in the lowest
      quartile (OR8.75, 95%CI 2.43, 31.58). More importantly, incorporating ANGPTL8
      into the conventional prediction model significantly increased the AUC for
      prediction of GDM (0.772vs 0.725; p = 0.019). CONCLUSIONS: Our study suggests
      that ANGPTL8 levels in early pregnancy are significantly and independently
      associated with risk of GDM at 24-28 weeks of gestation. Combining ANGPTL8 levels
      with conventional risk factors could thus improve the prediction of GDM.

PMID- 29167927
TI  - New diagnostic criteria for gestational diabetes mellitus and their impact on the
      number of diagnoses and pregnancy outcomes.
AB  - AIMS/HYPOTHESIS: Detection and management of gestational diabetes mellitus (GDM)
      are crucial to reduce the risk of pregnancy-related complications for both mother
      and child. In 2013, the WHO adopted new diagnostic criteria for GDM to improve
      pregnancy outcomes. However, the evidence supporting these criteria is limited.
      Consequently, these new criteria have not yet been endorsed in the Netherlands.
      The aim of this study was to determine the impact of these criteria on the number
      of GDM diagnoses and pregnancy outcomes. METHODS: Data were available from 10,642
      women who underwent a 75 g OGTT because of risk factors or signs suggestive of
      GDM. Women were treated if diagnosed with GDM according to the WHO 1999 criteria.
      Data on pregnancy outcomes were obtained from extensive chart reviews from 4,431
      women and were compared between women with normal glucose tolerance (NGT) and
      women classified into the following groups: (1) GDM according to WHO 1999
      criteria; (2) GDM according to WHO 2013 criteria; (3) GDM according to WHO 2013
      fasting glucose threshold, but not WHO 1999 criteria; and (4) GDM according to
      WHO 1999 2 h plasma glucose threshold (2HG), but not WHO 2013 criteria. RESULTS:
      Applying the new WHO 2013 criteria would have increased the number of diagnoses
      by 45% (32% vs 22%) in this population of women at higher risk for GDM. In
      comparison with women with NGT, women classified as having GDM based only on the
      WHO 2013 threshold for fasting glucose, who were not treated for GDM, were more
      likely to have been obese (46.1% vs 28.1%, p < 0.001) and hypertensive (3.3% vs
      1.2%, p < 0.001) before pregnancy, and to have had higher rates of gestational
      hypertension (7.8% vs 4.9%, p = 0.003), planned Caesarean section (10.3% vs 6.5%,
      p = 0.001) and induction of labour (34.8% vs 28.0%, p = 0.001). In addition,
      their neonates were more likely to have had an Apgar score <7 at 5 min (4.4% vs
      2.6%, p = 0.015) and to have been admitted to the Neonatology Department (15.0%
      vs 11.1%, p = 0.004). The number of large for gestational age (LGA) neonates was
      not significantly different between the two groups. Women potentially missed
      owing to the higher 2HG threshold set by WHO 2013 had similar pregnancy outcomes
      to women with NGT. These women were all treated for GDM with diet and 20.5%
      received additional insulin. CONCLUSIONS/INTERPRETATION: Applying the WHO 2013
      criteria will have a major impact on the number of GDM diagnoses. Using the
      fasting glucose threshold set by WHO 2013 identifies a group of women with an
      increased risk of adverse outcomes compared with women with NGT. We therefore
      support the use of a lower fasting glucose threshold in the Dutch national
      guideline for GDM diagnosis. However, adopting the WHO 2013 criteria with a
      higher 2HG threshold would exclude women in whom treatment for GDM seems to be
      effective.

PMID- 29167928
TI  - Pulmonary contusions after blunt chest trauma: clinical significance and
      evaluation of patient management.
AB  - INTRODUCTION: A pulmonary contusion is an entity defined as alveolar haemorrhage
      and pulmonary parenchymal destruction after blunt chest trauma. According to the
      literature, most pulmonary contusions can only be seen on a chest CT. The aim of
      this study was to evaluate the patients with pulmonary contusions, as well as
      their management, considering diagnostic and therapeutic options related to their
      outcomes, since we assumed, based on everyday clinical practice, that an
      'overdiagnosing' and 'overtreatment' attitude towards this injury could be
      present. PATIENTS AND METHODS: The research was a retrospective study including
      5042 patients admitted to the Department of Traumatology in the Clinical Hospital
      Centre Osijek, during a 3-year period. The medical data of the patients who
      suffered pulmonary contusion were evaluated considering significant
      characteristics, known risk factors, procedures undergone, and outcomes. RESULTS:
      During the 3-year period, 2% of all the admitted patients were diagnosed with a
      pulmonary contusion. In 54% of the cases, the patient suffered polytraumatic
      injuries. The pulmonary contusion was an isolated injury in 7% of the patients.
      In 31% of the cases, there was no liquidothorax or pneumothorax (isolated
      pulmonary contusion). In 89% of the patients the pulmonary contusion was
      diagnosed using a CT scan. In 68% of the patients there were no interventions
      regarding the thorax; thoracocentesis was performed in 25% of the cases, and
      pleural punction in 14% of the cases. 25% of the patients developed respiratory
      insufficiency and 16% required mechanical ventilation. Regarding isolated
      pulmonary contusions, respiratory insufficiency was present in 8% of the cases.
      CONCLUSIONS: We suggest that a pulmonary contusion seen on CT only has limited
      clinical significance and that the use of CT scans in diagnosing and follow-up of
      these patients should be re-evaluated. Further prospective and randomised studies
      should be conducted and the patients should be clinically evaluated, with the
      administration of supportive and antibiotic therapy, maintaining the fluid
      balance, the administration of diuretics, supportive oxygen therapy, pulmonary
      toilet, and physical therapy.

PMID- 29167929
TI  - Prediction of metabolism-induced hepatotoxicity on three-dimensional hepatic cell
      culture and enzyme microarrays.
AB  - Human liver contains various oxidative and conjugative enzymes that can convert
      nontoxic parent compounds to toxic metabolites or, conversely, toxic parent
      compounds to nontoxic metabolites. Unlike primary hepatocytes, which contain
      myriad drug-metabolizing enzymes (DMEs), but are difficult to culture and
      maintain physiological levels of DMEs, immortalized hepatic cell lines used in
      predictive toxicity assays are easy to culture, but lack the ability to
      metabolize compounds. To address this limitation and predict metabolism-induced
      hepatotoxicity in high-throughput, we developed an advanced miniaturized three
      dimensional (3D) cell culture array (DataChip 2.0) and an advanced metabolizing
      enzyme microarray (MetaChip 2.0). The DataChip is a functionalized micropillar
      chip that supports the Hep3B human hepatoma cell line in a 3D microarray format.
      The MetaChip is a microwell chip containing immobilized DMEs found in the human
      liver. As a proof of concept for generating compound metabolites in situ on the
      chip and rapidly assessing their toxicity, 22 model compounds were dispensed into
      the MetaChip and sandwiched with the DataChip. The IC50 values obtained from the
      chip platform were correlated with rat LD50 values, human C max values, and drug
      induced liver injury categories to predict adverse drug reactions in vivo. As a
      result, the platform had 100% sensitivity, 86% specificity, and 93% overall
      predictivity at optimum cutoffs of IC50 and C max values. Therefore, the
      DataChip/MetaChip platform could be used as a high-throughput, early stage,
      microscale alternative to conventional in vitro multi-well plate platforms and
      provide a rapid and inexpensive assessment of metabolism-induced toxicity at
      early phases of drug development.

PMID- 29167930
TI  - Planarian cholinesterase: molecular and functional characterization of an
      evolutionarily ancient enzyme to study organophosphorus pesticide toxicity.
AB  - The asexual freshwater planarian Dugesia japonica has emerged as a medium
      throughput alternative animal model for neurotoxicology. We have previously shown
      that D. japonica are sensitive to organophosphorus pesticides (OPs) and
      characterized the in vitro inhibition profile of planarian cholinesterase (DjChE)
      activity using irreversible and reversible inhibitors. We found that DjChE has
      intermediate features of acetylcholinesterase (AChE) and butyrylcholinesterase
      (BChE). Here, we identify two candidate genes (Djche1 and Djche2) responsible for
      DjChE activity. Sequence alignment and structural homology modeling with
      representative vertebrate AChE and BChE sequences confirmed our structural
      predictions, and show that both DjChE enzymes have intermediate sized catalytic
      gorges and disrupted peripheral binding sites. Djche1 and Djche2 were both
      expressed in the planarian nervous system, as anticipated from previous activity
      staining, but with distinct expression profiles. To dissect how DjChE inhibition
      affects planarian behavior, we acutely inhibited DjChE activity by exposing
      animals to either an OP (diazinon) or carbamate (physostigmine) at 1 uM for 4
      days. Both inhibitors delayed the reaction of planarians to heat stress.
      Simultaneous knockdown of both Djche genes by RNAi similarly resulted in a
      delayed heat stress response. Furthermore, chemical inhibition of DjChE activity
      increased the worms' ability to adhere to a substrate. However, increased
      substrate adhesion was not observed in Djche1/Djche2 (RNAi) animals or in
      inhibitor-treated day 11 regenerates, suggesting this phenotype may be modulated
      by other mechanisms besides ChE inhibition. Together, our study characterizes
      DjChE expression and function, providing the basis for future studies in this
      system to dissect alternative mechanisms of OP toxicity.

PMID- 29167931
TI  - The scope of Analytical and Bioanalytical Chemistry (ABC).

PMID- 29167932
TI  - Identification of phase-II metabolites of flavonoids by liquid chromatography-ion
      mobility spectrometry-mass spectrometry.
AB  - Flavonoids are a class of natural compounds with a broad range of potentially
      beneficial health properties. They are subjected to an extensive intestinal phase
      II metabolism, i.e., conjugation to glucuronic acid, sulfate, and methyl groups.
      Flavonoids and their metabolites can interact with drug transporters and thus
      interfere with drug absorption, causing food-drug interactions. The site of
      metabolism plays a key role in the activity, but the identification of the
      various metabolites remains a challenge. Here, we developed an analytical method
      to identify the phase-II metabolites of structurally similar flavonoids. We used
      liquid chromatography-ion-mobility spectrometry-mass spectrometry (LC-IMS-MS)
      analysis to identify phase-II metabolites of flavonols, flavones, and catechins
      produced by HT29 cells. We showed that IMS could bring valuable structural
      information on the different positional isomers of the flavonols and flavones.
      The position of the glucuronide moiety had a strong influence on the collision
      cross section (CCS) of the metabolites, with only minor contribution of hydroxyl
      and methyl moieties. For the catechins, fragmentation data obtained from MS/MS
      analysis appeared more useful than IMS to determine the structure of the
      metabolites, mostly due to the high number of metabolites formed. Nevertheless,
      CCS information as a molecular fingerprint proved to be useful to identify peaks
      from complex mixtures. LC-IMS-MS thus appears as a valuable tool for the
      identification of phase-II metabolites of flavonoids. Graphical abstract
      Structural identification of phase-II metabolites of flavonoids using LC-IMS-MS.

PMID- 29167933
TI  - Characterization of therapeutic protein AvidinOX by an integrated analytical
      approach.
AB  - AvidinOX, the oxidized derivative of Avidin, is a chemically modified
      glycoprotein, being currently under clinical investigation for targeted delivery
      of radioactive biotin to inoperable tumors. AvidinOX is produced by 4
      hydroxyazobenzene-2-carboxylic acid (HABA)-assisted sodium periodate oxidation of
      Avidin. The peculiar property of the periodate-generated glycol-split
      carbohydrate moieties to form Schiff's bases with amino groups of the tissue
      proteins allows to achieve a tissue half-life of 2 weeks compared to 2 h of
      native Avidin. Carbohydrate oxidation, along with possible minor amino acid
      modifications, introduces additional microheterogeneity in the glycoprotein
      structure, making its characterization even more demanding than for native
      glycoproteins. Aiming at the elucidation of the effects of oxidation conditions
      on the AvidinOX protein backbone and sugars, this microheterogeneous glycoprotein
      derivative was characterized for the first time using a combination of different
      analytical methods, including colorimetric methods, mass spectrometry, hollow
      fiber flow field-flow fractionation with UV and multi-angle laser scattering
      detection (HF5-UV-MALS), and NMR. The proposed integrated approach reveals
      structural features of AvidinOX relevant for its biological activity, e.g.,
      oxidized sites within both carbohydrate moieties and protein backbone and
      conformational stability, and will be considered as an analytical tool for
      AvidinOX industrial preparations. It is worth noting that this study enriches
      also the structural data of native Avidin published up-to-date (e.g., glycan
      structure and distribution, peptide fingerprint, etc.). Graphical abstract Scheme
      of phenylacetic hydrazide/MALDI-TOF approach for quantification of aldehydes in
      AvidinOX based on the determination of the number of hydrazone adducts between
      hydrazide reagent and aldehyde groups of protein.

PMID- 29167934
TI  - Study on oligomerization of glutamate decarboxylase from Lactobacillus brevis
      using asymmetrical flow field-flow fractionation (AF4) with light scattering
      techniques.
AB  - In this work, asymmetrical flow field-flow fractionation (AF4) coupled with
      UV/Vis, multi-angle light scattering (MALS), and differential refractive index
      (dRI) detectors (AF4-UV-MALS-dRI) was employed for analysis of glutamate
      decarboxylase (LbGadB) from Lactobacillus brevis (L. brevis). AF4 provided
      molecular weight (MW) (or size)-based separation of dimer, hexamer, and
      aggregates of LbGadB. The effect of pH on oligomerization of LbGadB was
      investigated, and then AF4 results were compared to those from molecular
      modeling. The MWs measured by AF4-UV-MALS-dRI for dimeric and hexameric forms of
      LbGadB were 110 and 350 kDa, respectively, which are in good agreements with
      those theoretically calculated (110 and 330 kDa). The molecular sizes determined
      by AF4-UV-MALS-dRI were also in good agreement with those obtained from molecular
      modeling (6 and 10 nm, respectively, for dimeric and hexameric from AF4-UV-MALS
      dRI and 6.4 * 7.6 and 7.6 * 13.1 nm from molecular modeling). The effects of
      temperature, salt type, and salt concentration on oligomerization of LbGadB were
      also investigated using dynamic light scattering (DLS). It was found that the
      hexameric form of LbGadB was most stable at pH 6 and in presence of NaCl or KCl.
      The results indicate that AF4, in combination of various online detectors
      mentioned above, provides an effective tool for monitoring of oligomerization of
      LbGadB under different conditions, such as temperature, pH, type of salts, and
      salt concentrations.

PMID- 29167935
TI  - Luminol, horseradish peroxidase, and glucose oxidase ternary functionalized
      graphene oxide for ultrasensitive glucose sensing.
AB  - Luminol, horseradish peroxidase (HRP), and glucose oxidase (GOx) ternary
      functionalized graphene oxide (HRP/GOx-luminol-GO) with excellent
      chemiluminescence (CL) activity and specific enzymatic property was prepared via
      a simple and general strategy for the first time. In this approach, luminol
      functionalized GO (luminol-GO) was prepared by gently stirring GO with luminol.
      Then HRP and GOx were further co-immobilized onto the surface of luminol-GO by
      storing HRP and GOx with luminol-GO at 4  degrees C overnight, to form HRP/GOx
      luminol-GO bionanocomposites. The synthesized HRP/GOx-luminol-GO could react with
      H2O2 generated from GOx catalyzed glucose oxidization reaction, to produce strong
      CL emission in the presence of co-immobilized HRP. Thus, we developed an
      ultrasensitive, homogeneous, reagentless, selective, and simple CL sensing system
      for glucose detection. The resulting biosensors exhibited ultra-wide linear range
      from 5.0 nM to 5.0 mM, and an ultra-low detection limit of 1.2 nM, which was more
      than 3 orders of magnitude lower than previously reported methods. Furthermore,
      the sensing system was successfully applied for the detection of glucose in human
      blood samples.

PMID- 29167936
TI  - Potential of dynamically harmonized Fourier transform ion cyclotron resonance
      cell for high-throughput metabolomics fingerprinting: control of data quality.
AB  - Due to the presence of pollutants in the environment and food, the assessment of
      human exposure is required. This necessitates high-throughput approaches enabling
      large-scale analysis and, as a consequence, the use of high-performance
      analytical instruments to obtain highly informative metabolomic profiles. In this
      study, direct introduction mass spectrometry (DIMS) was performed using a Fourier
      transform ion cyclotron resonance (FT-ICR) instrument equipped with a dynamically
      harmonized cell. Data quality was evaluated based on mass resolving power (RP),
      mass measurement accuracy, and ion intensity drifts from the repeated injections
      of quality control sample (QC) along the analytical process. The large DIMS data
      size entails the use of bioinformatic tools for the automatic selection of common
      ions found in all QC injections and for robustness assessment and correction of
      eventual technical drifts. RP values greater than 106 and mass measurement
      accuracy of lower than 1 ppm were obtained using broadband mode resulting in the
      detection of isotopic fine structure. Hence, a very accurate relative isotopic
      mass defect (RDeltam) value was calculated. This reduces significantly the number
      of elemental composition (EC) candidates and greatly improves compound
      annotation. A very satisfactory estimate of repeatability of both peak intensity
      and mass measurement was demonstrated. Although, a non negligible ion intensity
      drift was observed for negative ion mode data, a normalization procedure was
      easily applied to correct this phenomenon. This study illustrates the performance
      and robustness of the dynamically harmonized FT-ICR cell to perform large-scale
      high-throughput metabolomic analyses in routine conditions. Graphical abstract
      Analytical performance of FT-ICR instrument equipped with a dynamically
      harmonized cell.

PMID- 29167937
TI  - Novel comprehensive multidimensional liquid chromatography approach for
      elucidation of the microbosphere of shikimate-producing Escherichia coli
      SP1.1/pKD15.071 strain.
AB  - Shikimic acid is a intermediate of aromatic amino acid biosynthesis and the
      preferred starting material for production of the most commonly prescribed anti
      influenza drug, Tamiflu. Its six-membered carbocyclic ring is adorned with
      several chiral centers and various functionalities, making shikimic acid a
      valuable chiral synthon. When microbially-produced, in addition to shikimic acid,
      numerous other metabolites are exported out of the cytoplasm and accumulate in
      the culture medium. This extracellular matrix of metabolites is referred to as
      the microbosphere. Due to the high sample complexity, in this study, the
      microbosphere of shikimate-producing Escherichia coli SP1.1/pKD15.071 was
      analyzed by liquid chromatography and comprehensive two-dimensional liquid
      chromatography coupled to photodiode array and mass spectrometry detection. GC
      analysis of the trimethylsilyl derivatives was also carried out in order to
      support the elucidation of the selected metabolites in the microbosphere. The
      elucidation of the metabolic fraction of this bacterial strain might be of valid
      aid for improving, through genetic changes, the concentration and yield of
      shikimic acid synthesized from glucose. Graphical abstract.

PMID- 29167938
TI  - Multi-isotope calibration for inductively coupled plasma mass spectrometry.
AB  - Multi-isotope calibration (MICal) is a novel approach to calibration for
      inductively coupled plasma mass spectrometry (ICP-MS). In MICal, only two
      calibration solutions are required: solution A, composed of 50% v v-1 of sample
      and 50% v v-1 of a standard solution containing the analytes, and solution B,
      composed of 50% v v-1 of sample and 50% v v-1 of a blank solution. MICal is based
      on monitoring the signal intensities of several isotopes of the same analyte in
      solutions A and B. By plotting the analytical signals from solution A in the x
      axis, and from solution B in the y-axis, the analyte concentration in the sample
      is calculated using the slope of that graph and the concentration of the
      reference standard added to solution A. As both solutions contain the same amount
      of sample, matrix-matching is easily achieved. In this proof-of-concept study,
      MICal was applied to the determination of Ba, Cd, Se, Sn, and Zn in seven
      certified reference materials with different matrices (e.g., plant materials,
      flours, and water). In most cases, MICal results presented no statistical
      difference from the certified values at a 95% confidence level. The new strategy
      was also compared with traditional calibration methods such as external
      calibration, internal standardization and standard additions, and recoveries were
      generally better for MICal. This is a simple, accurate, and fast alternative
      method for matrix-matching calibration in ICP-MS. Graphical abstract Multi
      isotope calibration: fast and innovative matrix-matching calibration for ICP-MS.

PMID- 29167941
TI  - Comment on article by Parry et al.: Fungation in soft tissue sarcomas is
      associated with poor survival.

PMID- 29167940
TI  - The prognostic value of circulating myeloblasts in patients with myelodysplastic
      syndromes.
AB  - The prognostic value of peripheral blasts (PB) is not well-studied in patients
      with myelodysplastic syndromes (MDS). We evaluated the impact of PB on overall
      survival (OS) and transformation to acute myeloid leukemia (AML) in a large
      cohort. The MDS database at the Moffitt Cancer Center was retrospectively
      reviewed to identify patients with >= 1% PB (PB-MDS) and those without PB (BM
      MDS). We also assessed the correlation between PB and gene mutations. One
      thousand seven hundred fifty-eight patients were identified, among whom 13% had
      PB near the time of diagnosis. PB-MDS patients were more likely to be younger
      with trilineage cytopenia, complex karyotype, higher-risk disease, transfusion
      dependence, and therapy-related MDS. The rate of AML transformation was 49 vs.
      26% (p < 0.005) and median OS was 16.5 vs. 45.8 months (p < 0.005) in the PB-MDS
      and BM-MDS groups, respectively. In Cox regression analysis, the presence of PB
      was an independent prognostic covariate for OS, HR 1.57 (95% CI 1.2-2). Among 51
      patients with an available gene panel, the rate of >= 1 gene mutation in the PB
      MDS group (n = 4) was 100% compared to 81% in the BM-MDS group (n = 47). The
      presence of PB in MDS is an adverse independent prognostic variable that refines
      prognostic discrimination.

PMID- 29167939
TI  - The properdin pathway: an "alternative activation pathway" or a "critical
      amplification loop" for C3 and C5 activation?
AB  - This review is not intended to cover in detail all aspects of the discovery and
      evolution of our understanding of the "alternative pathway" of complement
      activation, there are many excellent reviews that do this (see Fearon (CRC Crit
      Rev Immunol 1:1-32, 1979), Pangburn and Muller-Eberhard (Springer Semin
      Immunopathol 7:163-192, 1984)), but instead to give sufficient background for
      current concepts to be put in context. The prevailing textbook view, of
      components having a primary role as an alternative "pathway" for C3 activation,
      is challenged, with an argument developed for the primary role of the system
      being that of providing a surface-dependent amplification loop for both C3 and C5
      activation. Whatever the mechanism by which the initial C3b molecule is
      generated, deposition onto a surface has the potential to target that surface for
      elimination. Elimination or escape from initial targeting is determined by a
      sophisticated and highly regulated amplification loop for C3 activation. This
      viewpoint of the system is then briefly developed to provide a context for
      therapeutic treatment of disease caused, at least in part, by dysregulated
      amplification of C3 activation, and to highlight some of the challenges that such
      therapies will face and need to address.

PMID- 29167943
TI  - Penetrating Crohn disease: does it occur in the absence of stricturing disease?
AB  - PURPOSE: To establish the relationship between penetrating complications and
      bowel luminal narrowing/stricturing disease in pediatric Crohn disease (CD).
      MATERIALS AND METHODS: This retrospective study was IRB-approved and HIPAA
      compliant with waiver of informed consent. CT and MRI examinations describing
      intra-abdominal penetrating complications in CD patients <= 18 years old between
      January 1, 2009 and March 31, 2016 were reviewed to document: type of
      complication, affected bowel segment, minimum bowel luminal diameter, maximum
      upstream diameter, location of penetrating complication relative to luminal
      narrowing, length of narrowed bowel segment, and the presence of active bowel
      wall inflammation. Data were summarized using descriptive statistics including
      means, standard deviations, as well as counts and percentages. RESULTS: A total
      of 52 penetrating complications were identified in 45 patients. Mean patient age
      was 15.7 +/- 2.2 years (range 11-18 years) with 25/45 (56%) boys. Nearly all
      penetrating complications (51/52, 98%) were associated with a minimum bowel
      luminal diameter of <= 2 mm, with no visible lumen in 26/52 (50%). Mean maximum
      upstream diameter was 2.8 +/- 0.8 cm (range 1.2-5.2 cm), and 17/52 (33%)
      penetrating complications were associated with > 3 cm upstream diameter. The mean
      ratio of maximum to minimum luminal diameter was 26.2 +/- 8.8 (range 3.6-52.0).
      Active intestinal inflammation was associated with 100% (52/52) of penetrating
      complications. Nearly every penetrating complication (51/52, 98%) involved the
      terminal or distal ileum. CONCLUSIONS: Penetrating complications in pediatric CD
      nearly always occur in the setting of considerable luminal narrowing or stricture
      and active intestinal inflammation.

PMID- 29167942
TI  - Prognostic analysis of different morphology of the necrotic-viable interface in
      osteonecrosis of the femoral head.
AB  - PURPOSE: The purpose of this study was to investigate the collapse progression in
      different morphologies of the necrotic-viable interface in osteonecrosis of the
      femoral head (ONFH). METHODS: A total of 168 patients (202 hips) with Association
      Research Circulation Osseous (ARCO) stage II ONFH were included. Ending with the
      collapse of the femoral head, all patients received conservative treatment but
      without surgical intervention and were followed for three to 91 months. Bilateral
      hip-joint radiographs and magnetic resonance imaging (MRI) were examined, and the
      largest layer of necrosis within the coronal section of MRI images was selected
      together with its anteroposterior radiograph to observe the morphology of the
      necrotic-viable interface. The morphology was divided into four types: I, type
      transverse; II, type "V"; III, type zigzag; IV, type closed. The collapse rate
      and the time to collapse in different morphologies were assessed. RESULTS: A
      total of 120 hips collapsed in two years or less, 61 were type-I, 51 were type
      II, and 8 were type-III. Non-collapse occurred in all 17 hips with type-IV ONFH
      during long-term follow-up. In 202 hips with ARCO stage-II ONFH, the collapse
      rate in type-I ONFH was significantly higher than that of type-II and type-III
      ONFH (P < 0.01 for both). The time to collapse was markedly shortened.
      CONCLUSIONS: The risk of ONFH-induced collapse is influenced by the morphology of
      the necrotic-viable interface. Effective mechanical support for preventing the
      collapse of the femoral head is necessary when the morphology of the necrotic
      viable interface is type transverse.

PMID- 29167944
TI  - Contrast-enhanced ultrasound of benign liver lesions.
AB  - Liver lesions are often incidentally detected on ultrasound examination and may
      be incompletely characterized, requiring further imaging. Contrast-enhanced
      ultrasound (CEUS) was recently approved by the Food and Drug Administration in
      the United States for liver lesion characterization. CEUS has the ability to
      characterize focal liver lesions and has been shown to be superior to color
      Doppler and power Doppler ultrasound in the detection of tumor vascularity.
      Differentiating benign from malignant liver lesions is essential to
      characterizing liver lesions. The CEUS imaging characteristics of benign liver
      lesions are reviewed, including hepatic cysts, hemangiomas, focal fat, focal
      nodular hyperplasia, hepatocellular adenomas, abscesses, and traumatic lesions.

PMID- 29167945
TI  - Letter to the editor response.

PMID- 29167946
TI  - Beaver tail liver.
AB  - Also known as the sliver of liver, beaver tail liver is an anatomic variation of
      the liver where its left lobe extends laterally to contact and enclose the
      spleen. Hepatic parenchyma is normal. It may be difficult to distinguish the two
      organs from each other when both have equal echogenicity or density in
      ultrasonography and computed tomography. Therefore, it may mimic a splenic trauma
      or a perisplenic hemorrhage or subcapsular hematoma within the splenic
      parenchyma.

PMID- 29167948
TI  - A Path to Actionable Climate Science: Perspectives from the Field.
AB  - The U.S. Department of the Interior Climate Science Centers (CSCs) work with
      natural and cultural resource managers and scientists to gather information and
      build tools needed to help fish, wildlife, and ecosystems adapt to the impacts of
      climate change. The CSCs prioritize the delivery of actionable science products
      (e.g., synthesized scientific information, maps, decision support tools, etc.)
      that are focused on key management priorities and co-produced by teams of
      scientists and managers. In the specific case of the Northwest CSC, we have been
      successful at promoting and supporting the co-production of actionable climate
      science at the individual project level, but it has been more difficult to
      replicate this success at the regional program level. Here we identify the most
      significant challenges in satisfying this mandate and propose the creation of a
      Science Advisory Panel to provide improved interface between resource managers
      and scientists engaged with the Northwest CSC.

PMID- 29167949
TI  - Survey of Beaver-related Restoration Practices in Rangeland Streams of the
      Western USA.
AB  - Poor condition of many streams and concerns about future droughts in the arid and
      semi-arid western USA have motivated novel restoration strategies aimed at
      accelerating recovery and increasing water resources. Translocation of beavers
      into formerly occupied habitats, restoration activities encouraging beaver
      recolonization, and instream structures mimicking the effects of beaver dams are
      restoration alternatives that have recently gained popularity because of their
      potential socioeconomic and ecological benefits. However, beaver dams and dam
      like structures also harbor a history of social conflict. Hence, we identified a
      need to assess the use of beaver-related restoration projects in western
      rangelands to increase awareness and accountability, and identify gaps in
      scientific knowledge. We inventoried 97 projects implemented by 32 organizations,
      most in the last 10 years. We found that beaver-related stream restoration
      projects undertaken mostly involved the relocation of nuisance beavers. The most
      common goal was to store water, either with beaver dams or artificial structures.
      Beavers were often moved without regard to genetics, disease, or potential
      conflicts with nearby landowners. Few projects included post-implementation
      monitoring or planned for longer term issues, such as what happens when beavers
      abandon a site or when beaver dams or structures breach. Human dimensions were
      rarely considered and water rights and other issues were mostly unresolved or
      addressed through ad-hoc agreements. We conclude that the practice and
      implementation of beaver-related restoration has outpaced research on its
      efficacy and best practices. Further scientific research is necessary, especially
      research that informs the establishment of clear guidelines for best practices.

PMID- 29167950
TI  - Hypoxia Increases Thyroid Cancer Stem Cell-Enriched Side Population.
AB  - INTRODUCTION: Hypoxic stress is a feature of rapidly growing thyroid tumours.
      Cancer progression is thought to be driven by a small population of tumour cells
      possessing stem cell properties. Hypoxia-inducible factors (HIFs) are important
      mediators of hypoxia. Both HIF-1alpha and HIF-2alpha have been reported to be
      expressed in thyroid cancers. There is growing evidence that the HIF pathway
      plays a significant role in the maintenance of thyroid cancer stem cells (CSC).
      METHODOLOGY: We have isolated thyroid CSC from a papillary thyroid cancer-derived
      cell line (BCPAP) and an anaplastic thyroid cancer-derived cell line (SW1736) as
      side population (SP) cells (a putative stem cell population) and treated them
      with cobalt chloride (II) to induce hypoxia. RESULTS AND DISCUSSION: We observed
      an increase in the SP of cells within the thyroid cancer cell lines following
      induction of hypoxia.

PMID- 29167951
TI  - Radioembolization Versus Bland Embolization for Hepatic Metastases from Small
      Intestinal Neuroendocrine Tumors: Short-Term Results of a Randomized Clinical
      Trial.
AB  - BACKGROUND: Radioembolization (RE) with intra-arterial administration of 90Y
      microspheres is a promising technique for the treatment of liver metastases from
      small intestinal neuroendocrine tumors (SI-NET) not amenable to surgery or local
      ablation. However, studies comparing RE to other loco-regional therapies are
      lacking. The aim of this randomized study was to compare the therapeutic response
      and safety after RE and bland hepatic arterial embolization (HAE), and to
      investigate early therapy-induced changes with diffusion-weighted MRI (DWI-MRI).
      METHODS: Eleven patients were included in a prospective randomized controlled
      pilot study, six assigned to RE and five to HAE. Response according to RECIST 1.1
      using MRI or CT at 3 and 6 months post-treatment was recorded as well as changes
      in DWI-MRI parameters after 1 month. Data on biochemical tumor response,
      toxicity, and side effects were also collected. RESULTS: Three months after
      treatment, all patients in the HAE group showed partial response according to
      RECIST while none in the RE group did (p = 0.0022). After 6 months, the response
      rates were 4/5 (80%) and 2/6 (33%) in the HAE and RE groups, respectively (NS).
      DWI-MRI metrics could not predict RECIST response, but lower pretreatment ADC(120
      800) and larger ADC(0-800) increase at 1 month were related to larger decrease in
      tumor diameter when all tumors were counted. CONCLUSION: HAE resulted in
      significantly higher RECIST response after 3 months, but no difference compared
      to RE remained after 6 months. These preliminary findings indicate that HAE
      remains a safe option for the treatment of liver metastases from SI-NET, and
      further studies are needed to establish the role of RE and the predictive value
      of MR-DWI.

PMID- 29167952
TI  - Growth of Focal Nodular Hyperplasia is Not a Reason for Surgical Intervention,
      but Patients Should be Referred to a Tertiary Referral Centre.
AB  - BACKGROUND: When a liver lesion diagnosed as focal nodular hyperplasia (FNH)
      increases in size, it may cause doubt about the initial diagnosis. In many cases,
      additional investigations will follow to exclude hepatocellular adenoma or
      malignancy. This retrospective cohort study addresses the implications of growth
      of FNH for clinical management. METHODS: We included patients diagnosed with FNH
      based on >=2 imaging modalities between 2002 and 2015. Characteristics of
      patients with growing FNH with sequential imaging in a 6-month interval were
      compared to non-growing FNH. RESULTS: Growth was reported in 19/162 (12%)
      patients, ranging from 21 to 200%. Resection was performed in 4/19 growing FNHs;
      histological examination confirmed FNH in all patients. In all 15 conservatively
      treated patients, additional imaging confirmed FNH diagnosis. No adverse outcomes
      were reported. No differences were found in characteristics and presentation of
      patients with growing or non-growing FNH. CONCLUSION: This study confirms that
      FNH may grow significantly without causing symptoms. A significant increase in
      size should not have any implications on clinical management if confident
      diagnosis by imaging has been established by a tertiary benign liver
      multidisciplinary team. Liver biopsy is only indicated in case of doubt after
      state-of-the-art imaging. Resection is deemed unnecessary if the diagnosis is
      confirmed by multiple imaging modalities in a tertiary referral centre.

PMID- 29167953
TI  - Result of Thoracic Endovascular Aortic Repair for Patients with Esophageal
      Cancer.
AB  - BACKGROUND: Bleeding from the thoracic aorta is potentially fatal in patients
      with advanced esophageal cancer. Thoracic endovascular aortic repair (TEVAR) was
      recently applied for aortic invasion by esophageal cancer. However, only a few
      case reports have been published. This study was performed to clarify the
      effectiveness and safety of TEVAR for patients with advanced esophageal cancer.
      METHODS: We retrospectively reviewed 18 patients who underwent TEVAR for
      esophageal cancer. We also performed a literature search and reviewed 21 similar
      cases. RESULTS: From 2007 to 2016, 10 patients were treated on an emergent basis
      for aortic hemorrhage (salvage group) and 8 patients underwent urgent
      prophylactic surgery (prophylactic group). Hemostasis was achieved in all cases.
      One (10%) patient in the salvage group died of aspiration pneumonia on
      postoperative day 1, while all patients in the prophylactic group survived for >1
      month. The median survival period in the salvage and prophylactic group was 3.25
      and 11.10 months, respectively. The longest survivor was still alive 9 years
      after TEVAR and chemoradiotherapy. No fatal adverse events or negative impacts on
      subsequent treatment for esophageal cancer occurred. CONCLUSIONS: TEVAR is
      feasible, safe, and effective in preventing fatal aortic hemorrhage secondary to
      esophageal cancer invasion, although it is palliative in most cases. Because the
      outcomes of emergent TEVAR after bleeding tended to be worse in the salvage than
      in prophylactic group, prophylactic TEVAR may be considered a viable treatment
      option for patients with aortic invasion by advanced esophageal cancer.

PMID- 29167954
TI  - No implant migration and good subjective outcome of a novel customized femoral
      resurfacing metal implant for focal chondral lesions.
AB  - PURPOSE: Managing focal cartilage injuries in the middle-aged patient poses a
      challenge. Focal prosthetic inlay resurfacing has been proposed to be a bridge
      between biologics and conventional joint arthroplasty. Patient selection and
      accurate implant positioning is crucial to avoid increased contact pressure to
      the opposite cartilage surface. A customized femoral condyle implant for focal
      cartilage injuries was designed to precisely fit each patient's individual size
      and location of damage. The primary objective was to assess implant safety
      profile, surgical usability of the implant and instruments, and implant migration
      with radiostereometric analysis (RSA). METHODS: Ten patients 36-56 years with
      focal chondral defects, ICRS 3-4 of the femoral cartilage and failed earlier
      conservative or surgical interventions with VAS pain > 40. The patients were
      followed for 2 years with subjective outcome measures (VAS, EQ5D, KOOS) and RSA.
      The customized implant and guide instruments were manufactured by computer-aided
      design/computer-aided manufacturing (CAD/CAM) techniques using MRI data. RESULTS:
      VAS, EQ5D and KOOS showed improvements that reached significance for VAS (p <=
      0.001), Tegner (p = 0.034) and the KOOS subscores ADL (p = 0.0048), sport and
      recreation (p = 0.034) and quality of life (p = 0.037). VAS and KOOS scores
      improved gradually at 3, 6 and 12 months. The improvements in EQ5D, KOOS pain and
      KOOS symptoms did not reach statistical significance. No infections, deep venous
      thrombosis or other complications occured in the postoperative period. No
      radiographic signs of damage to the opposing tibial cartilage was noted. The
      surgical usability of implants and instruments were good. RSA did not show any
      implant migration. CONCLUSION: This is the first clinical report of a new
      customized, focal knee resurfacing system. The short-term implant safety and
      patient-related outcome measures showed good-to-excellent results. LEVEL OF
      EVIDENCE: Prospective case series, Level 4.

PMID- 29167955
TI  - Step-wise medial collateral ligament needle puncturing in extension leads to a
      safe and predictable reduction in medial compartment pressure during TKA.
AB  - PURPOSE: Medial soft tissue release in a varus deformity knee during total knee
      arthroplasty is essential for accurate balancing of the reconstruction. This
      study attempts to quantify the effect of sequential needle puncturing of the
      medial collateral ligament (MCL) using a pressure sensor insert (Verasense by
      OrthoSensor) and gap measurement under tension. METHODS: Cruciate-retaining
      arthroplasties were placed in 14 cadaveric knees. The MCL was elongated by step
      wise perforation, in five sets of five perforations, with the use of an 18-gauge
      needle, followed by valgus stress. Following the fifth set of needle
      perforations, blade perforation was performed on the remaining tense fibers of
      the MCL. Following each step-wise perforation, corresponding medial compartment
      pressures and gap measurements under tension were recorded. RESULTS: Sensor
      measurements correlated closely with step-wise tissue release (R = 0.73, p <
      0.0001), and a significant decrease in pressure was found in early needle
      puncturing (mean 49 N after 5, 83 N after 15, p values < 0.05), although changes
      diminished at later stages of needle perforation (90 N after 20). Gap measurement
      demonstrated small gradual changes with early puncturing, but showed significant
      opening in the later stages of release. There was minimal variation in pressure
      or gap measurements in flexion versus extension. This finding suggests that MCL
      needle puncture will not lead to unequal gaps between flexion and extension.
      There were no cases of MCL over-release after 15 punctures, one case after 20
      punctures, and three after blade perforation. CONCLUSION: Needle puncturing of
      the MCL in extension for up to 15 punctures can be a safe and predictable way to
      achieve medial opening when balancing a varus knee during TKA as demonstrated in
      this cadaveric model. Blade perforation should be used with caution to avoid over
      release. The needle puncture method can be used by surgeons to achieve reliable
      reductions in medial compartment pressures, to help achieve a balanced TKA, with
      minimal risk of over-release.

PMID- 29167957
TI  - A Safe and Effective Technique.

PMID- 29167956
TI  - Double-Pedicle Tram Flap Breast Reconstruction: Following.
AB  - After using various techniques with various results, Bostwick's principles for
      breast reconstruction were used in mastectomy cases and their early results are
      presented. The breast reconstructions were performed to 12 cases, of which eight
      patients had one or two risk factors and four had more. The double-pedicle
      technique was used in the former and vascular delay preceding double-pedicle
      technique was used in the latter. No vascular compromises, arterial or venous,
      were observed on the flaps in the acute phase and no fat necrosis ensued lately.
      All patients were satisfied with these principles and we did not observe any
      problems with the flaps. We have concluded that Bostwick's principles offered a
      reliable and minimal risk basis for breast reconstructive surgeons.

PMID- 29167958
TI  - Reply to Troilius.

PMID- 29167961
TI  - Passing on the Torch!!

PMID- 29167964
TI  - How Does Oyster Shell Immobilize Cadmium?
AB  - The exact mechanism of cadmium (Cd) immobilization by oyster shell (OS) has not
      been reported. The effect of OS on Cd immobilization and the exact mechanism
      should be known before applying remediation technology using OS to Cd
      contaminated soils. Therefore, the objective of this study was to elucidate the
      mechanism of Cd immobilization by OS. Three grams of OS (< 0.84 mm) was reacted
      with 30 mL of 0-3.56 mg Cd L-1 solution at 25  degrees C for 48 h. Cadmium
      adsorption increased with increasing initial concentration of Cd in solution. The
      X-ray diffraction patterns clearly demonstrated that precipitation of CdCO3 did
      not take place in suspensions of OS after reacting with up to 3.56 mol Cd L-1.
      Interestingly, we found formation of Ca0.67Cd0.33CO3 crystalline in suspension of
      OS after reacting with maximum initial Cd concentrations. Precipitation and
      chemisorption might contribute to Cd immobilization together. However, we feel
      confident that chemisorption is the major mechanism by which Cd immobilization
      occurs with OS. In conclusion, OS could be an effective bioadsorbent to
      immobilize Cd through formation of geochemically stable Cd mineral.

PMID- 29167965
TI  - Impact of Suspended Solids on the Use of LuminoTox to Detect Toxicity of
      Micropollutants.
AB  - There is an increasing need for tools to monitor toxicity of contaminants of
      emerging concern (CECs) in wastewater. The purpose of this work was to assess
      interferences in the presence of total solids (TS) and total suspended solids
      (TSS) in the LuminoTox at concentrations typical of those found in municipal
      secondary effluent (SE) and to evaluate a simple sample enrichment method for
      increased CEC sensitivity. 4 or 10 ug/L atrazine in different TS concentrations
      and in corresponding filtrates (TSS removed) exhibited equivalent toxicities.
      Because the only difference between these two fractions is the TSS, this result
      demonstrates that, generally, this fraction does not induce toxicity nor
      interfere with the bioassay. At constant medium-low TS, the LuminoTox was able to
      detect the presence of 4 ug/L of atrazine but could not distinguish the change in
      atrazine concentration between 4 and 6 ug/L. No inhibition was observed in the
      presence of a mix of 14 CECs each at 0.23 ug/L. However, upon sample enrichment
      by lyophilization (50*), an inhibition of 81 +/- 3% was observed. The enriched SE
      alone (not spiked with CECs) led to an inhibition of 49 +/- 1%, indicating the
      detection of the CEC contribution to toxicity after sample preconcentration. The
      LuminoTox is a promising tool for monitoring SE; however, if the intent is to
      detect CECs, enrichment method optimization is required.

PMID- 29167966
TI  - Planning Prostate Artery Embolisation: Is it Essential to Perform a Pre
      procedural CTA?
AB  - PURPOSE: A highly variable prostatic artery origin coupled with frequent
      anastomoses to adjacent organs makes prostate artery embolisation a challenging
      procedure. Despite CT angiography facilitating procedural planning, it is not
      performed in all centres. Therefore, we explored the utility of prostatic CT
      angiography by assessing its capacity to identify the prostatic arteries and
      highlight troublesome anastomoses. MATERIALS AND METHODS: A retrospective review
      of patients undergoing prostate artery embolisation for symptoms of benign
      prostatic obstruction between June 2012 and October 2016 was conducted, with
      analysis of the pre-procedural CT angiography. CT findings were compared with
      subsequent intraprocedural angiography to assess the accuracy with which CT
      angiography predicts the origin of prostatic arteries and identifies anastomoses.
      RESULTS: In total, 110 patients underwent prostate artery embolisation, with pre
      procedural CT angiography acquired in all patients, enabling assessment of 220
      pelvic sides of hemiprostatic arterial supply. Mean dose length product was 808.4
      mGycm. CT angiography successfully identified prostatic arterial supply in
      214/220 pelvic sides, an accuracy of 97.3%. Anastomoses of prostatic vessels were
      suggested by CT angiography in 52 pelvic sides. These were confirmed by angiogram
      in 49/52 sides (94.2%). CT angiography demonstrated a sensitivity of 59.0% and
      specificity of 94.2% for anastomoses detection. CONCLUSION: CT angiography prior
      to embolisation reliably predicts the arterial anatomy and facilitates procedural
      planning. Therefore, it should be a considered as a pre-procedural investigation
      for patients undergoing prostate artery embolisation. Sensitivity is low for
      predicting anastomoses, so careful periprocedural evaluation of the target
      vessels is still required.

PMID- 29167967
TI  - Safety and Feasibility of Chemoembolization with Doxorubicin-Loaded Small
      Calibrated Microspheres in Patients with Hepatocellular Carcinoma: Results of the
      MIRACLE I Prospective Multicenter Study.
AB  - PURPOSE: The MIRACLE I pilot study was designed as a preliminary investigation of
      safety and efficacy of Embozene TANDEM microspheres loaded with doxorubicin for
      treatment of locally untreatable (i.e., unresectable and not suitable for local
      thermal ablation) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients
      with locally untreatable HCC (mono- or bilobar disease, ECOG performance status 0
      2, Child-Pugh score < 11) were eligible for this single-arm multicenter study.
      DEB-TACE was performed with 75 um Embozene TANDEM loaded with 150 mg of
      doxorubicin. RESULTS: Twenty-five subjects with 41 tumors were treated (mean age
      65 years); 16, 52, and 32% had BCLC A, B, and C status, respectively. Child-Pugh
      status was A for 64%, B for 32%, and C for 4%; 40% had ascites. About 92% had
      disease localized to one liver lobe. Most (72%) underwent <= 2 DEB-TACE
      procedures. Average doxorubicin dose was 124.5 +/- 36.1 mg (median 150 mg) per
      procedure. Two patients had procedure-related SAE (liver necrosis, worsening of
      liver insufficiency) within 30 days of the first DEB-TACE procedure. Six-month
      freedom from procedure-related SAE or death was 68% (one hepatic encephalopathy,
      five deaths). Tumor response or stable disease was achieved in 95% (20/21) of
      subjects. Freedom from tumor progression or death at 6 months was 76%. The one
      year survival rate was 56% overall and 73% among patients without ascites at
      baseline. CONCLUSION: MIRACLE I results suggest that Embozene TANDEM microspheres
      loaded with doxorubicin can provide good local tumor control in a heterogeneous
      group of patients with locally untreatable HCC. LEVEL OF EVIDENCE: Level 2b,
      Individual cohort study.

PMID- 29167968
TI  - The Value of Hybrid Angio-CT in Preoperative Detection and Localization of
      Insulinomas: A Single-Center Retrospective Study.
AB  - OBJECTIVE: To investigate the performance of hybrid angio-CT in preoperative
      detection and localization for insulinomas. METHODS: Fifty-four postoperative
      pathology-confirmed patients from April 2015 to March 2017 were retrospectively
      reviewed; all patients underwent angio-CT with administration of contrast media
      in SMA, GDA and SA due to negative, inconclusive or controversial findings by
      several preoperative diagnostic methods including TAUS, CEUS, EUS, ECT, EMRI and
      DSA. Surgery was used as gold standard for localization of insulinomas; detection
      sensitivity and localization accuracy of angio-CT were assessed and compared with
      other preoperative image options. RESULTS: Fifty-six benign insulinomas (mean
      diameter, 15.8 mm) in 54 patients (18 men and 36 women) were found according to
      surgical results; the overall detection sensitivity of TAUS, CEUS, EUS, ECT, EMRI
      and DSA was 21.4, 78.4, 79.2, 70.0, 79.2 and 72.2%, respectively. The overall
      localization accuracy was 14.3, 58.8, 68.8, 60.0, 75.0 and 44.4%, respectively. A
      total of 53 tumors were detected by angio-CT, 51 tumors were accurately located,
      and the overall detection sensitivity and localization accuracy of angio-CT was
      94.4 and 90.7%, which was significantly higher than that of all other
      preoperative diagnostic methods (p < 0.05). No any serious complications occurred
      during angio-CT. CONCLUSION: Our study indicates the great potential value of
      angio-CT in the preoperative detection and localization of insulinomas; angio-CT
      can be used as a preferred invasive diagnostic method.

PMID- 29167969
TI  - Association of incident hip fracture with the estimated femoral strength by
      finite element analysis of DXA scans in the Osteoporotic Fractures in Men (MrOS)
      study.
AB  - : Finite element model can estimate bone strength better than BMD. This study
      used such a model to determine its association with hip fracture risk and found
      that the strength estimate provided limited improvement over the hip BMDs in
      predicting femoral neck (FN) fracture risk only. INTRODUCTION: Bone fractures
      occur only when it is loaded beyond its ultimate strength. The goal of this study
      was to determine the association of femoral strength, as estimated by finite
      element (FE) analysis of DXA scans, with incident hip fracture as a single
      condition or with femoral neck (FN) and trochanter (TR) fractures separately in
      older men. METHODS: This prospective case-cohort study included 91 FN and 64 TR
      fracture cases and a random sample of 500 men (14 had a hip fracture) from the
      Osteoporotic Fractures in Men study during a mean +/- SD follow-up of 7.7 +/- 2.2
      years. We analysed the baseline DXA scans of the hip using a validated plane
      stress, linear-elastic FE model of the proximal femur and estimated the femoral
      strength during a sideways fall. RESULTS: The estimated strength was
      significantly (P < 0.05) associated with hip fracture independent of the TR and
      total hip (TH) BMDs but not FN BMD, and combining the strength with BMD did not
      improve the hip fracture prediction. The strength estimate was associated with FN
      fractures independent of the FN, TR and TH BMDs; the age-BMI-BMD adjusted hazard
      ratio (95% CI) per SD decrease of the strength was 1.68 (1.07-2.64), 2.38 (1.57,
      3.61) and 2.04 (1.34, 3.11), respectively. This association with FN fracture was
      as strong as FN BMD (Harrell's C index for the strength 0.81 vs. FN BMD 0.81) and
      stronger than TR and TH BMDs (0.8 vs. 0.78 and 0.81 vs. 0.79). The strength's
      association with TR fracture was not independent of hip BMD. CONCLUSIONS:
      Although the strength estimate provided additional information over the hip BMDs,
      its improvement in predictive ability over the hip BMDs was confined to FN
      fracture only and limited.

PMID- 29167970
TI  - Independent association of bone mineral density and trabecular bone score to
      vertebral fracture in male subjects with chronic obstructive pulmonary disease.
AB  - : Osteoporosis is a major comorbidity of chronic obstructive pulmonary disease
      (COPD), but the mechanism of bone fragility is unknown. We demonstrated that
      trabecular bone score, a parameter of bone quality, was associated with systemic
      inflammation and was a significant determinant of vertebral fracture independent
      of bone mineral density. INTRODUCTION: COPD is a major cause of secondary
      osteoporosis. However, the mechanism of bone fragility is unclear. We previously
      reported that vertebral fracture was highly prevalent in male COPD patients. To
      obtain clues to the mechanism of COPD-associated osteoporosis, we attempted to
      identify determinants of prevalent vertebral fracture in this study. METHODS: In
      this cross-sectional study, we recruited 61 COPD males and examined pulmonary
      function, vertebral fractures, bone mineral density (BMD), trabecular bone score
      (TBS), bone turnover markers, and inflammatory parameters. Determinants of the
      bone parameters were examined by multivariable analyses. RESULTS: The prevalence
      of any and grade 2 or 3 fractures was 75.4 and 19.7%, respectively. Osteoporosis
      and osteopenia defined by BMD were present in 37.7 and 39.3%, respectively. TBS
      was significantly lower in higher Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) stages compared to GOLD 1. Multivariable logistic regression
      analysis revealed that both TBS and BMD were independent determinants of grade 2
      or 3 vertebral fractures (OR = 0.271, 95%CI 0.083-0.888, p = 0.031; OR = 0.242,
      95%CI 0.075-0.775, p = 0.017) after adjustment for age. Correlates of TBS
      included age, BMD, high-sensitivity C-reactive protein (hsCRP), pulmonary
      function parameters, parathyroid hormone, and Tracp-5b. In multivariable
      regression analysis, hsCRP was the only independent determinant of TBS besides
      age and BMD. In contrast, independent determinants of BMD included body mass
      index and, to a lesser extent, 25-hydroxyvitamin D. CONCLUSION: Both BMD and TBS
      were independently associated with grade 2 or 3 vertebral fracture in COPD male
      subjects, involving distinct mechanisms. Systemic inflammation, as reflected by
      increased hsCRP levels, may be involved in deterioration of the trabecular
      microarchitecture in COPD-associated osteoporosis, whereas BMD decline is most
      strongly associated with weight loss.

PMID- 29167971
TI  - Abaloparatide-SC improves trabecular microarchitecture as assessed by trabecular
      bone score (TBS): a 24-week randomized clinical trial.
AB  - : In a phase 2 trial of 222 postmenopausal women with osteoporosis aged 55 to 85
      years randomized to one of three different doses of abaloparatide-SC,
      subcutaneous teriparatide, or placebo for 24 weeks, abaloparatide-SC resulted in
      improvements in skeletal microarchitecture as measured by the trabecular bone
      score. INTRODUCTION: Subcutaneous abaloparatide (abaloparatide-SC) increases
      total hip and lumbar spine bone mineral density and reduces vertebral and non
      vertebral fractures. In this study, we analyzed the extent to which abaloparatide
      SC improves skeletal microarchitecture, assessed indirectly by trabecular bone
      score (TBS). METHODS: This is a post hoc analysis of a phase 2 trial of 222
      postmenopausal women with osteoporosis aged 55 to 85 years randomized to
      abaloparatide-SC (20, 40, or 80 MUg), subcutaneous teriparatide (20 MUg), or
      placebo for 24 weeks. TBS was measured from lumbar spine dual X-ray
      absorptiometry (DXA) images in 138 women for whom the DXA device was TBS software
      compatible. Assessments were made at baseline, 12 and 24 weeks. Between-group
      differences were assessed by generalized estimating equations adjusted for
      relevant baseline characteristics, and a pre-determined least significant change
      analysis was performed. RESULTS: After 24 weeks, TBS increased significantly by
      2.27, 3.14, and 4.21% versus baseline in participants on 20, 40, and 80 MUg
      abaloparatide-SC daily, respectively, and by 2.21% in those on teriparatide (p <
      0.05 for each). The TBS in the placebo group declined by 1.08%. The TBS increase
      in each treatment group was significantly higher than placebo at 24 weeks (p <
      0.0001 for each) after adjustment for age, BMI, and baseline TBS. A dose-response
      was observed at 24 weeks across the three doses of abaloparatide-SC and placebo
      (p = 0.02). The increase in TBS in the abaloparatide-SC 80 MUg group was
      significantly greater than TPTD (p < 0.03). CONCLUSIONS: These results are
      consistent with an effect of abaloparatide-SC to improve lumbar spine skeletal
      microarchitecture, as assessed by TBS.

PMID- 29167972
TI  - Translating patient-reported outcomes to improve patient care and urogynecologic
      research.

PMID- 29167973
TI  - Renaissance of the autologous pubovaginal sling.

PMID- 29167974
TI  - Long-term outcome of vaginal mesh or native tissue in recurrent prolapse: a
      randomized controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: Our aim was to evaluate clinically relevant long
      term outcomes of transvaginal mesh or native tissue repair in women with
      recurrent pelvic organ prolapse (POP). METHODS: We performed a 7-year follow-up
      of a randomized controlled trial on trocar-guided mesh placement or native tissue
      repair in women with recurrent POP. Primary outcome was composite success,
      defined as absence of POP beyond the hymen, absence of bulge symptoms, and
      absence of retreatment for POP. Secondary outcomes were adverse events, pain, and
      dyspareunia. Multiple imputation was used for missing data of composite success
      and pain; estimates are presented with 95% confidence intervals (CI). RESULTS:
      Between August 2006 and July 2008, 194 women were randomized; 190 underwent
      surgery. At 7 years, 142 (75%) were available for analysis, of whom, the primary
      outcome could be calculated in 127. Composite success was 53% (95% CI 41, 66) for
      mesh and 54% (95% CI 42, 65) for native tissue. Repeat surgery for POP was 25%
      for mesh and 16% for native tissue (difference 9%; 95% CI -5, 23) and occurred in
      untreated compartments in the mesh group and treated compartments in the native
      tissue group. Mesh exposure rate was 42%; pain with mesh 39% and native tissue
      50% (difference - 11%, 95% CI -27, 6); dyspareunia with mesh 20% and native
      tissue 17% (difference 3%, 95% CI -9, 17). CONCLUSIONS: Seven-year composite
      success rates appeared similar for mesh and native tissue. Mesh did not reduce
      long-term repeat surgery rates due to de novo POP in nonmesh-treated vaginal
      compartments. Mesh exposure rates were high, though significant differences in
      pain and dyspareunia were not detected. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov , NCT00372190.

PMID- 29167975
TI  - Use of an iPadTM application in preoperative counseling for pelvic reconstructive
      surgery: a randomized trial.
AB  - INTRODUCTION AND HYPOTHESIS: The goal of this study was to evaluate whether the
      addition of an iPadTM application to the informed consent process for pelvic
      organ prolapse (POP) surgery improves patient understanding and retention of
      information compared with standard verbal counseling (SVC) alone. METHODS:
      Patients scheduled for POP surgery were randomized to SVC alone or SVC augmented
      with an iPadTM application. Prior to counseling, immediately following
      counseling, and 6 weeks after surgery, patients completed a written quiz testing
      their understanding of POP and surgical repair (worst score 0; best score 20).
      Primary outcome was score change from pre- to immediately postcounseling.
      Secondary outcomes were patient satisfaction and score change from postcounseling
      to 6 weeks after surgery. Twenty-six patients per group were needed to detect a
      2.8-point difference in score change between groups (80% power; alpha = 0.05).
      RESULTS: Sixty patients were randomized, and 57 patients (29 SVC; 28 iPad) were
      included in the final analysis. There was no significant difference in score
      change between groups immediately postcounseling. Six weeks after surgery,
      patients in the iPad group had more deterioration of score (iPad -4.0 +/- 2.8 vs.
      SVC -0.6 +/- 2.3 points; p = 0.02). Both groups reported similar satisfaction
      with counseling. CONCLUSIONS: The addition of a POP-based iPadTM application to
      the informed consent process for POP surgery did not improve patient
      comprehension immediately postcounseling and resulted in poorer retention of
      information 6 weeks after surgery compared with SVC alone.

PMID- 29167976
TI  - Temporary closure of colostomy with suture before colostomy takedown improves the
      postoperative outcomes.
AB  - PURPOSE: Temporary loop colostomy is a common surgical procedure used to avoid
      complications in high-risk distal anastomosis as well as pelvic inflammation.
      Issues regarding postoperative outcomes of colostomy takedown have been widely
      discussed in the literature, wound infection especially. Temporary closure of
      colostomy with suture before takedown was adopted in our study, which provided
      excellent traction to aid mobilization of stomy and avoided stool spillage to
      downgrade the wound classification to "clean contamination." We aimed to
      determine the effects of the procedure on postoperative outcomes. METHODS: This
      was a prospective case-control study at a single tertiary medical center.
      Patients presenting for elective colostomy takedown were included. Allis clamp (n
      = 50) or silk suture (n = 60) was applied to mobilize the colostomy, and results
      were compared. Operative time and wound infection rate were measured as primary
      postoperative outcomes. Univariate and multivariate analyses were used to
      demonstrate the association between the two groups and outcomes. RESULTS: In
      univariate analyses, significantly shorter operative time (median = 57 min, p =
      0.003) and lower postoperative wound infection rate (3%, p = 0.03) were noted in
      the group receiving silk suture. Multivariate analyses results showed that silk
      suture was significantly associated with both operative time (B = - 8.5, p =
      0.01) and wound infection (odds ratio = 0.18, p = 0.04). CONCLUSION: With the
      advantage of enhancing traction and decreasing contamination, the temporary
      closure of colostomy with suture improved takedown outcomes, including a shorter
      operative time and lower wound infection rate.

PMID- 29167977
TI  - Thoracic epidural haematoma due to a subclavian steal syndrome and secondary
      formed thoracic collateral circuits, coincidence or consequence: a case report.
AB  - Despite profound diagnostics, the aetiology of spinal epidural haematoma (SEH)
      often remains unknown. In this case, diagnostics revealed an SEH at the fifth and
      sixth thoracic levels due to a subclavian steal syndrome with a tortuous vascular
      loop between the sixth thoracic intercostal artery and the costocervical arteries
      deriving from the left subclavian artery with plump arteries in the epidural
      space. The patient underwent decompression surgery and a percutaneous
      transluminal angioplasty. The patient showed good recovery at follow-up. The SEH
      was a result of secondary formed thoracic collateral circuits with epidural
      involvement due to a subclavian steal syndrome.

PMID- 29167978
TI  - Long-term follow-up of multimodality treatment for multiple sclerosis-related
      trigeminal neuralgia.
AB  - BACKGROUND: The treatment for multiple sclerosis-related trigeminal neuralgia (MS
      TN) is less efficacious and associated with higher recurrence rates than
      classical TN. No consensus has been reached in the literature on the choice
      procedure for MS-TN patients. The aim of this study was to assess the incidence
      and surgical outcomes of medically refractory MS-TN. METHODS: Patient records
      were retrospectively reviewed for all Manitobans undergoing first procedure for
      medically refractory MS-TN between 2000 and 2014. Subsequent procedures were then
      recorded and analyzed in this subgroup of patients. The primary outcome measure
      was time to treatment failure. RESULTS: The incidence of medically refractory MS
      TN was 1.2/million/year. Twenty-one patients with 26 surgically treated sides
      underwent first rhizotomy including 13 GammaKnife and 13 percutaneous rhizotomies
      comprised of ten glycerol injections and three balloon compressions. Subsequent
      procedures were required on 23 sides (88%), including 24 GammaKnife, 19 glycerol
      injections, 25 balloon compressions, two microvascular decompressions, and four
      open partial surgical rhizotomies with a total of 99 surgeries on 26 sides
      (range, 1-12 each). CONCLUSIONS: The majority of MS-TN patients become medically
      refractory and require multiple repeat surgical procedures. MS-TN procedures were
      associated with high rates of pain recurrence and our data suggests reoperation
      within 1 year is often necessary. Optimal management strategy in this patient
      population remains to be determined. Patients need to be counseled on managing
      expectations as treatments commonly afford only temporary relief.

PMID- 29167979
TI  - Good results with minimally invasive unicompartmental knee resurfacing after 10
      year follow-up.
AB  - The current study was designed to determine (1) 10-year implant survival and (2)
      patient's self-reported functional outcome in a single surgeon's consecutive
      cohort of patients who had undergone minimally invasive unicondylar resurfacing
      with a modified cementation technique utilizing a cobalt-chromium femur/inlaid
      all-PE tibia, fixed-bearing unicompartmental prosthesis. We included 344
      consecutive patients (361 knees) who had received the study device between
      January 2002 and December 2005 in this retrospective study. After 10 years, 78
      patients (78 knees) had died, 59 (59 knees) were lost to follow-up and four (four
      knees) did not participate. Thirteen knees (11 patients) were revised after a
      mean of 5.8 +/- 1.9 years. Hence, the study population at follow-up comprised 192
      patients (207 knees). Ten-year implant survival was 94.6% (95% confidence
      interval, 90.9-96.8%). The Forgotten Joint Score and Oxford Knee Score were 68.9
      +/- 28.9 and 39 +/- 9.1, respectively. Excellent survivorship and clinical
      outcomes were obtained with UKA with an inlaid all-PE tibia with a modified
      cementation technique.

PMID- 29167980
TI  - Role of isolated percutaneous autologous platelet concentrate in delayed union of
      long bones.
AB  - PURPOSE: The objective of this study is to evaluate the efficacy of percutaneous
      platelet concentrate (PC) injection in increasing the chances of attaining union
      in delayed union of long bones and to know whether the time taken for union
      decreases with use of PC. METHODS: Forty delayed unions (15-30 weeks old) were
      randomized into a study group in which autologous PC prepared by blood bank
      centrifuge was percutaneously injected at the fracture site under image
      intensifier after activation with 10% calcium gluconate and a control group where
      patients were observed over time. Follow-up was every 6 weeks till fracture
      union. At each follow-up visit clinical and radiological parameters of union were
      assessed. RESULTS: Percentage union was 78% (18/23) in PC group and 59% (10/17)
      in control group, respectively (p = 0.296). The mean time to fracture union
      treated with PC (15.33 +/- 9.91 weeks) was not different from the control group
      (13.10 +/- 7.21 weeks; p = 0.540). In the PC group union is seen in 12 weeks
      after PC injection in 60 per cent of the cases. CONCLUSION: Isolated percutaneous
      PC injection increases union rates in delayed union of long bones. The results
      were, however, not statistically significant but show high positive association.
      Further studies are required to recommend routine use of PC injection.

PMID- 29167981
TI  - Transcriptional induction of two phosphate transporter 1 genes and enhanced root
      branching in grape plants inoculated with Funneliformis mosseae.
AB  - We investigated the effects of the arbuscular mycorrhizal fungus (AMF)
      Funneliformis mosseae on the growth and root architecture of plantlets of the
      grape rootstock 41B MGt under hydroponic conditions, and analyzed the concomitant
      expression of putative mycorrhizal-specific phosphate transporter 1 (PHT1) genes.
      In vitro propagated plantlets were acclimatized to ex vitro culture before AMF
      inoculation and grown under low phosphate (Pi) nutrition conditions during 6
      weeks. Grape roots could be efficiently colonized by F. mosseae in this culture
      system, as shown by high mycorrhization frequency and intensity. The presence of
      many arbuscules in the cortex was coupled with high-level expression of two PHT1
      genes in grape roots. These two very similar genes, named VvPht1-1 and VvPht1-2,
      present P1BS and MYCS regulatory motifs in their promoter, consistent with a
      specific role in the mycorrhizal pathway of Pi uptake. Although AMF inoculation
      significantly increased shoot growth, no effect on root biomass was observed.
      However, inoculated grapes exhibited an enhanced branched root system compared
      with non-inoculated controls, with a twofold higher number of tips and a higher
      proportion of fine roots usually involved in nutrient uptake from the soil. Taken
      together, these results suggest that root colonization by F. mosseae improved
      grape growth by favoring the uptake of Pi from the substrate via VvPht1-1 and
      VvPht1-2 high-level expression.

PMID- 29167982
TI  - Successional changes in trophic interactions support a mechanistic model of post
      fire population dynamics.
AB  - Models based on functional traits have limited power in predicting how animal
      populations respond to disturbance because they do not capture the range of
      demographic and biological factors that drive population dynamics, including
      variation in trophic interactions. I tested the hypothesis that successional
      changes in vegetation structure, which affected invertebrate abundance, would
      influence growth rates and body condition in the early-successional,
      insectivorous gecko Nephrurus stellatus. I captured geckos at 17 woodland sites
      spanning a succession gradient from 2 to 48 years post-fire. Body condition and
      growth rates were analysed as a function of the best-fitting fire-related
      predictor (invertebrate abundance or time since fire) with different combinations
      of the co-variates age, sex and location. Body condition in the whole population
      was positively affected by increasing invertebrate abundance and, in the adult
      population, this effect was most pronounced for females. There was strong support
      for a decline in growth rates in weight with time since fire. The results suggest
      that increased early-successional invertebrate abundance has filtered through to
      a higher trophic level with physiological benefits for insectivorous geckos. I
      integrated the new findings about trophic interactions into a general conceptual
      model of mechanisms underlying post-fire population dynamics based on a long-term
      research programme. The model highlights how greater food availability during
      early succession could drive rapid population growth by contributing to
      previously reported enhanced reproduction and dispersal. This study provides a
      framework to understand links between ecological and physiological traits
      underlying post-fire population dynamics.

PMID- 29167983
TI  - Climate change can alter predator-prey dynamics and population viability of prey.
AB  - For many organisms, climate change can directly drive population declines, but it
      is less clear how such variation may influence populations indirectly through
      modified biotic interactions. For instance, how will climate change alter
      complex, multi-species relationships that are modulated by climatic variation and
      that underlie ecosystem-level processes? Caribou (Rangifer tarandus), a keystone
      species in Newfoundland, Canada, provides a useful model for unravelling
      potential and complex long-term implications of climate change on biotic
      interactions and population change. We measured cause-specific caribou calf
      predation (1990-2013) in Newfoundland relative to seasonal weather patterns. We
      show that black bear (Ursus americanus) predation is facilitated by time-lagged
      higher summer growing degree days, whereas coyote (Canis latrans) predation
      increases with current precipitation and winter temperature. Based on future
      climate forecasts for the region, we illustrate that, through time, coyote
      predation on caribou calves could become increasingly important, whereas the
      influence of black bear would remain unchanged. From these predictions,
      demographic projections for caribou suggest long-term population limitation
      specifically through indirect effects of climate change on calf predation rates
      by coyotes. While our work assumes limited impact of climate change on other
      processes, it illustrates the range of impact that climate change can have on
      predator-prey interactions. We conclude that future efforts to predict potential
      effects of climate change on populations and ecosystems should include assessment
      of both direct and indirect effects, including climate-predator interactions.

PMID- 29167984
TI  - X-ray micro-computed-tomography in pediatric surgery: a new tool for studying
      embryos.
AB  - PURPOSE: The embryology of common congenital malformations is discussed
      controversially. Studies are hampered by a shortage of study material and
      techniques which require partial or complete preparation and therewith
      destruction of embryos. X-ray micro-computed-tomography (uCT) is a technical
      opportunity keeping the embryos intact. Thus, the aim of this study was to assess
      the applicability of uCT in embryonic research compared to the anatomical
      information obtained by scanning electron microscopy (SEM). METHODS: Chicken,
      rat, mouse and sheep embryos, processed either for SEM studies or as whole
      embryos, were imaged in three-dimensional (3D) using uCT. The obtained two
      dimensional (2D) digital datasets were volume rendered by tomographic
      reconstruction software and studied using analysis software. RESULTS: All embryos
      were uCT scanned without technical problems. The quality of the uCT images (image
      contrast, anatomical details) was excellent, but varied depending on age and
      species studied. uCT imaging allowed a more comprehensive
      anatomical/morphological analysis but showed less surface details compared to
      SEM. CONCLUSION: uCT is a technique suitable and innovative for pediatric
      surgical research, which allows detailed evaluation of entire embryos without
      time- and specimen-consuming micro-dissection. Samples prepared for SEM can be
      used for uCT and vice versa.

PMID- 29167985
TI  - Short-term outcome after cystectomy: comparison of early oral feeding in an
      enhanced recovery protocol and feeding using Bengmark nasojejunal tube.
AB  - PURPOSE: Cystectomy for bladder cancer is associated with a high risk of
      postoperative complications. Standardized perioperative protocols, such as
      enhanced recovery after surgery (ERAS) protocols, aim to improve postoperative
      outcome. Postoperative feeding strategies are an important part of these
      protocols. In this two-centre study, we compared complications and length of
      hospital stay (LOS) between an ERAS protocol with early oral nutrition and a
      protocol with early enteral feeding with a Bengmark nasojejunal tube. METHODS: We
      retrospectively reviewed 154 consecutive patients who underwent cystectomy for
      bladder cancer in two hospitals (Hospital A and B) between 2014 and 2016.
      Hospital A uses an ERAS protocol (n = 45), which encourages early introduction of
      an oral diet. Hospital B uses a fast-track protocol comprising feeding with a
      Bengmark nasojejunal tube (Bengmark-protocol, n = 109). LOS and complications
      according to Clavien classification were compared between protocols. RESULTS:
      Overall 30-day complication rates in the ERAS and Bengmark protocol were similar
      (64.4 and 67.0%, respectively; p = 0.463). The rate of postoperative ileus (POI)
      was significantly lower in the Bengmark protocol (11.9% vs. 34.4% in the ERAS
      protocol, p = 0.009). This association remained significant after adjustment for
      other variables (odds ratio 0.32, 95% confidence interval 0.11-0.96; p = 0.042).
      Median LOS did not differ significantly between protocols (10 days vs. 11 days in
      the ERAS and Bengmark protocols, respectively; p = 0.861). CONCLUSIONS: Early
      oral nutrition in Hospital A was well tolerated. However, the Bengmark protocol
      was superior with respect to occurrence of POI. A prospective study may clarify
      whether the lower rate of POI was due to the use of early nasojejunal tube
      feeding or other reasons.

PMID- 29167986
TI  - Amidase activity is essential for medial localization of AmiC in Caulobacter
      crescentus.
AB  - Bacterial cell division is a complex process brought about by the coordinated
      action of multiple proteins. Separation of daughter cells during the final stages
      of division involves cleavage of new cell wall laid down at the division septum.
      In E. coli, this process is governed by the action of N-acetylmuramoyl-L-alanine
      amidases AmiA/B/C, which are regulated by their LytM activators EnvC and NlpD.
      While much is known about the regulation of septum cleavage in E. coli, the
      mechanism of daughter cell separation is not clear in Caulobacter crescentus, a
      dimorphic crescent-shaped bacterium. In this work, we characterized the role of
      AmiC, the only annotated amidase in C. crescentus. AmiC from C. crescentus is
      functional in E. coli and restores cell separation defects seen in E. coli
      amidase mutants, suggesting that AmiC has septum splitting activity. The medial
      localization of AmiC was independent of DipM, an LytM domain-containing
      endopeptidase. Our results indicate that enzymatic activity is essential for
      medial recruitment of AmiC. Overexpression of AmiC causes cell separation defects
      and formation of chains. Finally, overexpression of AmiC in cells inhibited for
      cell division leads to lysis. Collectively, our findings reveal that regulation
      of daughter cell separation in C. crescentus differs from that of E. coli and can
      serve as a model system to study bacterial cytokinesis.

PMID- 29167987
TI  - The geographical vector in distribution of genetic diversity for Clonorchis
      sinensis.
AB  - Clonorchis sinensis, the causative agent of clonorchiasis, is one of the most
      important parasites that inhabit countries of East and Southeast Asia. In this
      study, we validated the existence of a geographical vector for C. sinensis using
      the partial cox1 mtDNA gene, which includes a conserved region. The samples of
      parasite were divided into groups corresponding to three river basins, and the
      size of the conserved region had a strong tendency to increase from the
      northernmost to the southernmost samples. This indicates the availability of the
      geographical vector in distribution of genetic diversity. A vector is a quantity
      that is characterized by magnitude and direction. Geographical vector obtained in
      cox1 gene of C. sinensis has both these features. The reasons for the occurrence
      of this feature, including the influence of intermediate and definitive hosts on
      vector formation, and the possibility of its use for clonorchiasis monitoring are
      discussed. Graphical abstract ?.

PMID- 29167988
TI  - The electronic transport properties of B40 fullerenes with chalcogens as anchor
      atoms.
AB  - Fullerenes are the most popular molecules to use in applications related to
      molecular electronics because of their superconductive nature. These molecules
      show a diverse range of properties, including optical, electronic, and structural
      characteristics. In this work, we focused on the electronic transport properties
      of molecular devices consisting of the fullerene B40 or B40 with different anchor
      atoms between two gold electrodes in a two-probe configuration. The elements used
      as anchor atoms in the B40 molecules were oxygen, selenium, and sulfur, i.e.,
      chalcogens. The current characteristics of these fullerene-based molecular
      devices were calculated and analyzed. The analysis highlighted the superior
      electrical conductivity of the pure B40 device compared to the devices based on
      its chalcogen-anchored variants. The conductivities of the molecular devices were
      ranked as follows: pure B40 > selenium-anchored > sulfur-anchored > oxygen
      anchored B40. It was also noted that the devices based on B40 and its chalcogen
      anchored variants gave nonzero conductance values at zero bias. These results
      pave the way for the application of these molecules in future nanodevices
      utilizing extremely small bias voltages.

PMID- 29167989
TI  - TCNE-modified graphene as an adsorbent for N2O molecule: a DFT study.
AB  - Adsorption behavior of nitrous oxide (N2O) on pristine graphene (PG) and
      tetracyanoethylene (TCNE) modified PG surfaces is investigated using density
      functional theory. A number of initial adsorbate geometries are considered on
      both surfaces and the most stable ones are chosen upon calculation of the
      adsorption energies (Eads). N2O is found to adsorb in a weakly exoergic process
      (Eads ~ -3.18 kJ mol-1) at the equilibrium distance of 3.52 A on the PG surface.
      N2O adsorption can be greatly enhanced with the presence of a TCNE molecule (Eads
      = -87.00 kJ mol-1). Mulliken charge analysis confirms that adsorption of N2O is
      not accompanied by distinct charge transfer from the surfaces to the molecule (?
      0.001 ?e? for each case). Moreover, on the basis of calculated changes in the
      HOMO/LUMO energy gap, it is found that electronic properties of PG and TCNE
      modified PG are not sensitive toward adsorption of N2O, indicating that both
      surfaces are not good enough to introduce as an N2O detector. However, the
      considerable amount of Eads in TCNE modified PG can be a guide to the design of
      graphene-based adsorbents for N2O capture.

PMID- 29167991
TI  - A comparison of bioclimatic potential in two global regions during the late
      twentieth century and early twenty-first century.
AB  - Changes in the general circulation of the atmosphere have been taking place
      during the latter part of the twentieth century and the early part of the twenty
      first century. In the Belgorod region of Southwest Russia, this has been
      manifested in the more frequent occurrence of stationary anticyclones, including
      those referred to as blocking anticyclones, especially during the summer season.
      Also, there has been a general increase in regional temperatures during the
      growing season over the period mentioned above, and combined with the more
      frequent occurrence of anticyclones has led to less humid conditions. In the
      Missouri region of the Central USA, variability in the circulation on differing
      time scales within the Eastern Pacific plays a strong role in the conditions that
      impact the growing season. As a result of changes in climate and climate
      variability, the benefit to agriculture during this period produces mixed results
      for both regions. This work will evaluate the growing season conditions using
      indexes that combine growing season temperature and precipitation such as the
      hydrothermal coefficient (HTC) and the bioclimatic potential (BCP). Also, the
      interannual variability of these indexes in both regions was examined. In the
      Belgorod region, the increase in temperature combined with little change in
      precipitation produced mixed results in interpreting these indexes. This was
      accompanied by more variable conditions as revealed by these indexes in the early
      twenty-first century. In the Missouri region, there was little trend in either
      index over the time period and the tendency was toward less climatic variability
      in the HTC and BCP.

PMID- 29167990
TI  - Histologic analysis has a prognostical value in colorectal biopsies assessed for
      suspicion of graft-versus-host disease.
AB  - Gastrointestinal (GI) graft-versus-host-disease (GVHD) is a common and severe
      complication of allogeneic hematopoietic stem cell transplantation, but clinical
      and histological features are unspecific. The aim of this study was to correlate
      the histological GI GVHD grade with the clinical outcomes. In a retrospective
      study of 112 patients with clinically suspected GI GVHD, colonic biopsies were
      reviewed by three pathologists without knowledge of the corresponding clinical
      data and classified in four scores, according to the NIH Consensus Project
      recommendations: no GVHD, possible, probable, and unequivocal GVHD. At the end of
      the study, the histological and clinical data were confronted with the following
      results: clinical diagnosis of GI GVHD was established for 70 patients (62.5%)
      and histological scores correlated well with the clinical diagnosis (p < 0.001)
      and particularly with the prognosis (p < 0.05).When severe lesions were observed,
      the 1 year overall survival declined to 9%. None of the features reported in the
      literature to support GVHD diagnosis, eosinophil count, endocrine cells
      aggregate, immunohistochemical analysis (cytomegalovirus, CD123, chromogranin),
      did not help us for diagnosis. So routine histopathology alone without
      immunohistochemistry is a strong and reproducible tool to diagnose GI GVHD with
      the help of clinical and biological information, and most importantly,
      histological grading proved to be a powerful prognostic value.

PMID- 29167992
TI  - Slow correction of severe spastic hyperlordosis in an adult by means of
      magnetically expandable rods.
AB  - BACKGROUND: We describe a case of severe and progressive lumbar hyperlordosis
      (160 degrees ) in a 28-year-old female university student with cerebral palsy.
      Her main complaints were abdominal wall pain and increasing inability to sit in
      her custom wheelchair. METHOD: When deciding on our opinion about the most
      promising treatment strategy, we contemplated slow continued correction by means
      of percutaneously expandable magnetic rods (MAGEC) after the index surgery as a
      key component of a satisfactory correction in this severe and rigid curve. After
      an initial radical release and partial correction, a release and correction
      procedure was required for the bilateral hip flexion contracture. A final in situ
      posterior fusion was performed as a second spinal procedure, once the desired
      final correction at 66 degrees  of lumbar lordosis was achieved. RESULT: Three
      years after the completion of surgery, the patient has a stable clinical and
      radiological result as well as a solid posterior fusion on CT. CONCLUSION: This
      is the first case published in which percutaneous magnetic distraction was
      successfully used in an adult patient.

PMID- 29167993
TI  - Group 3 medulloblastoma in a patient with a GYS2 germline mutation and glycogen
      storage disease 0a.
AB  - Glycogen storage disease (GSD) 0a is a rare congenital metabolic disease with
      symptoms in infancy and childhood caused by biallelic GYS2 germline variants. A
      predisposition to cancer has not been described yet. We report here a boy with
      GSD 0a, who developed a malignant brain tumor at the age of 4.5 years. The tumor
      was classified as a group 3 medulloblastoma, and the patient died from cancer 27
      months after initial tumor diagnosis. This case appears interesting as group 3
      medulloblastoma is so far not known to arise in hereditary syndromes and the
      biology of sporadic group 3 medulloblastoma is largely unknown.

PMID- 29167994
TI  - Congenital Zika virus infection: a neuropathological review.
AB  - BACKGROUND: A relationship between Zika virus (ZikV) infection in pregnancy and
      the occurrence of microcephaly was established during the Zika outbreak in Brazil
      (2015-2016). Neuropathological findings in congenital Zika syndrome helped to
      understand its pathogenetic mechanisms. RESULTS: The most relevant postmortem
      findings in the central nervous system (CNS) of fetuses and neonates infected
      with ZikV early in gestation are microcephaly with ex-vacuo ventriculomegaly and
      large head circumference associated with obstructive hydrocephalus due to severe
      midbrain and aqueduct distortion. Babies with severe brain lesions are born with
      arthrogryposis. Histologically, there is extensive destruction of the hemispheric
      parenchyma, calcifications, various disturbances of neuronal migration, reactive
      gliosis, microglial hyperplasia and occasional perivascular cuffs of lymphocytes,
      also in the meninges. Hypoplastic lesions secondary to the lack of descending
      nerve fibers include small basis pontis, pyramids and spinal corticospinal
      tracts. Cerebellar hypoplasia is also common. Severe nerve motor nerve cell loss
      is observed in the anterior horn of the spinal cord. CONCLUSION: A spectrum of
      neuropathological changes, from severe microcephaly to obstructive hydrocephalus
      was observed. The severity of the lesions is directly related to the gestational
      age, the most severe occurring when the mother is infected in the first
      trimester. Infection of progenitor cells at the germinal matrix was demonstrated.
      The lack of spinal motor neurons is responsible for fetal acynesia and consequent
      arthrogryposis.

PMID- 29167995
TI  - Ultrasound-guided placement of ventricular catheters in first-time pediatric VP
      shunt surgery.
AB  - PURPOSE: Ventriculo-peritoneal (VP) shunts are effective for treatment of
      hydrocephalus in all age groups; however, they are associated with complications,
      a common one being ventricular catheter (VC) obstruction. VC position is likely
      to influence VC survival; however, most VCs are positioned freehand without
      guidance. This paper describes the accuracy of ultrasound guidance for VC
      placement and the impact of tip location on VC occlusion rate. METHODS: This is a
      retrospective cohort study of hydrocephalic children with first-time VP shunt and
      ultrasound-guided VC placement. Data recorded were age, sex, cause of
      hydrocephalus, side (left or right) and location (frontal or occipital) of VC,
      and exact postoperative position within the ventricle on first postoperative
      imaging: middle of ventricle (optimal position), near or touching the medial or
      lateral ventricle wall, within the third ventricle, and at the contralateral
      side. RESULTS: Of the 128 screened patients, 85 had a first postoperative imaging
      that clearly defined the VC position and were included. The follow-up was at
      least 12 months. Seventy-three percent of VCs were placed on the right and 71%
      via a frontal burhole. Eighty-three of 85 VC tips (95%) were in the intended
      ventricle, 61% at optimal position. Nine of 85 VCs (10%) obstructed within the
      first 12 months. Seven of nine (78%) obstructed VCs were located in a nonoptimal
      position (p = 0.016). Two of nine (22%) obstructed VCs entered through a frontal
      and seven of nine (78%) through an occipital burrhole (p = 0.016). CONCLUSION:
      Ultrasound-guided VC placement is as precise as frameless navigated placement.
      The optimal VC position was associated to a significant lower VC obstruction
      rate. The frontal position was superior to the occipital. Intraoperative US
      guidance is fast with almost no extra time and no extra cost. US-guided VC
      placement should become standard of care in VP shunt surgery.

PMID- 29167996
TI  - Unexpected finding: dermoid component within a filar lipoma.

PMID- 29167997
TI  - The association of kyphosis assessed in supine and standing positions with future
      activities of daily living dependence: the Kurabuchi Study.
AB  - : We investigated the longitudinal association of noninvasively evaluated
      kyphotic posture with future dependence in activities of daily living and death
      in a community-dwelling older Japanese. We found that the association with
      outcomes varied according to the types of kyphotic posture. INTRODUCTION: We have
      previously found an association between severe kyphosis and future dependence in
      activities of daily living (ADL) in people who manifest the condition in the
      supine position (structural curvature). However, because some people show severe
      kyphosis only in the standing position (postural curvature), we combined our
      noninvasively obtained kyphosis measurements from participants in the supine
      position (block method) with those obtained from participants in the standing
      position (kyphosis index) to determine whether not only structural curvature but
      also postural curvature is associated with ADL dependence and death. METHODS:
      Between 2005 and 2006, we carried out health evaluations of adults aged 65 years
      or older in Kurabuchi Town, Japan: 792 participants (337 males, 455 females) who
      were independent in ADL at baseline and underwent evaluation of kyphotic posture
      were followed up until March 2014 (mean follow-up: 7.5 years). Participants who
      experienced one or more admissions to a nursing home, certification of a need for
      long-term care/support, or a decline in the Katz ADL Index during the follow-up
      period were defined as being dependent in ADL. RESULTS: A flat back (straight
      spine in a standing position) and structural curvature were associated with
      future ADL dependence, but postural curvature was not. The multivariate-adjusted
      odds ratios (95% confidence interval) compared with physiological curvature
      (physiological curvature in a standing position) as the reference were 1.72 (1.04
      2.86) for a flat back and 2.76 (1.59-4.79) for structural curvature. A weak
      association with death was observed in those with structural curvature.
      CONCLUSIONS: Our results suggest that the prognoses of people with kyphosis
      differ according to the type of kyphotic posture.

PMID- 29167998
TI  - Association of stroke subtypes with risk of hip fracture: a population-based
      study in Taiwan.
AB  - : Stroke is a critical issue of physical disability. This study aimed to
      investigate the association of stroke subtypes and hip fracture by using the
      Taiwan National Health Insurance Research Database. Significantly higher risks of
      hip fracture were found for female gender and intracerebral hemorrhagic stroke
      patients. INTRODUCTION: Previous studies reported the increased hip fracture (HF)
      after acute stroke. Increased falling tendency immobilization-related sarcopenia
      and underlying comorbidities are related to HF in stroke patients. In the present
      study, we explored the association of different stroke subtypes and several
      comorbidities with poststroke HF. METHODS: A population-based study was conducted
      using National Health Insurance Research Database (NHIRD) of Taiwan. First, we
      identified 17,168 patients diagnosed as having a stroke between January 1, 2002,
      and December 31, 2010. Then, we randomly selected 51,504 controls that never had
      a stroke and matched these controls to stroke patients in a 1:3 ratio by age (+/-
      1 year old) and gender. Cox proportional hazards model was used to estimate
      hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Stroke patients had
      a significantly higher risk of HF (HR = 1.69). Female and male stroke patients
      had incidence rate ratios (IRRs) of 2.05 and 1.82 for HF, respectively.
      Significantly increased IRRs of 1.82, 1.52, and 2.63 for HF were found for stroke
      patients with 0, 1, and >= 2 comorbidities, respectively. All stroke patients,
      ischemic stroke patients, and intracerebral hemorrhagic (ICH) patients had HF
      risks of 1.65, 1.60, and 2.34, respectively. CONCLUSION: Overall, stroke
      significantly increases the incidence of HF, and the risk of HF is significantly
      higher in ICH patients and female gender. We should identify stroke patients at
      risk of HF and pay more attention to prevent them from fall in poststroke long
      term care.

PMID- 29167999
TI  - Integrated Analysis of Healthcare Efficiency: A Systematic Review.
AB  - Data Envelopment Analysis (DEA) has been used as a performance measurement tool
      in efficiency assessment of healthcare systems. However, over the years,
      researchers and health practitioners presented the theoretical and methodological
      limitations of DEA that limits the full view of healthcare efficiency. To address
      these limitations, a commonly used strategy is to integrate other statistical
      methods and techniques with DEA to provide better efficiency evaluation. This
      paper reviews 57 studies with DEA applications in the healthcare industry to
      illustrate the integrated analysis of healthcare efficiency. With DEA as the
      central method, regression models in conjunction with statistical tests are
      commonly used. Input-oriented radial DEA models using predominantly capacity
      related inputs and activity-related outputs and following either constant return
      to scale or variable return to scale assumptions are mostly applied to measure
      healthcare efficiency.

PMID- 29168000
TI  - Raman Mapping Analysis of Graphene-Integrated Silicon Micro-Ring Resonators.
AB  - We present a Raman mapping study of monolayer graphene G and 2D bands, after
      integration on silicon strip-waveguide-based micro-ring resonators (MRRs) to
      characterize the effects of the graphene transfer processes on its structural and
      optoelectronic properties. Analysis of the Raman G and 2D peak positions and
      relative intensities reveal that the graphene is electrically intrinsic where it
      is suspended over the MRR but is moderately hole-doped where it sits on top of
      the waveguide structure. This is suggestive of Fermi level 'pinning' at the
      graphene-silicon heterogeneous interface, and we estimate that the Fermi level
      shifts down by approximately 0.2 eV from its intrinsic value, with a
      corresponding peak hole concentration of ~ 3 * 1012 cm-2. We attribute variations
      in observed G peak asymmetry to a combination of a 'stiffening' of the E 2g
      optical phonon where the graphene is supported by the underlying MRR waveguide
      structure, as a result of this increased hole concentration, and a lowering of
      the degeneracy of the same mode as a result of localized out-of-plane 'wrinkling'
      (curvature effect), where the graphene is suspended. Examination of graphene
      integrated with two different MRR devices, one with radii of curvature r = 10 MUm
      and the other with r = 20 MUm, indicates that the device geometry has no
      measureable effect on the level of doping.

PMID- 29168001
TI  - Pronounced Photovoltaic Response from Multi-layered MoTe2 Phototransistor with
      Asymmetric Contact Form.
AB  - In this study, we fabricate air-stable p-type multi-layered MoTe2 phototransistor
      using Au as electrodes, which shows pronounced photovoltaic response in off-state
      with asymmetric contact form. By analyzing the spatially resolved photoresponse
      using scanning photocurrent microscopy, we found that the potential steps are
      formed in the vicinity of the electrodes/MoTe2 interface due to the doping of the
      MoTe2 by the metal contacts. The potential step dominates the separation of
      photoexcited electron-hole pairs in short-circuit condition or with small V sd
      biased. Based on these findings, we infer that the asymmetric contact cross
      section between MoTe2-source and MoTe2-drain electrodes is the reason to form non
      zero net current and photovoltaic response. Furthermore, MoTe2 phototransistor
      shows a faster response in short-circuit condition than that with higher biased V
      sd within sub-millisecond, and its spectral range can be extended to the infrared
      end of 1550 nm.

PMID- 29168002
TI  - Lasing and Transport Properties of Poly[(9,9-dioctyl-2,7-divinylenefluorenylene)
      alt-co-(2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene)] (POFP) for the Application
      of Diode-Pumped Organic Solid Lasers.
AB  - This paper demonstrates the lasing and transport properties of a green conjugated
      polymer, namely POFP. High photoluminescence yields and excellent electron
      transport of POFP film make it promising for gain media. Low threshold value of
      4.0 MUJ/cm2 for amplified spontaneous emissions under a pulsed Nd:YAG laser at
      355 nm was obtained, as well as a high Q-factor of 159. An inverted waveguide
      microcavity scheme has been developed to fabricate diode-pumped organic solid
      lasers (OSLs) using POFP. Gain narrowing with significant radiance increase was
      observed in the devices, giving evidence of the interference enhancement induced
      by microcavity and the lasing properties of POFP.

PMID- 29168003
TI  - Numerical Study of an Efficient Solar Absorber Consisting of Metal Nanoparticles.
AB  - We propose and theoretically investigate an efficient solar light absorber based
      on a multilayer structure consisting of tungsten nanoparticle layers and SiO2
      layers. According to our calculation, average absorbance over 94% is achieved in
      the wavelength range between 400 and 2500 nm for the proposed absorber. The
      excellent performance of the absorber can be attributed to the localized surface
      plasmon resonance as well as the Fabry-Perot resonance among the metal-dielectric
      metal layers. We compare the absorbing efficiency of tungsten nanosphere absorber
      with absorbers consisting of the other metal nanoparticles and conclude that iron
      can be an alternative material for tungsten in solar energy systems for its
      excellent absorbing performance and the similar optical properties as tungsten.
      Besides, a flat multilayer absorber is designed for comparison, and it is also
      proved to have a good absorbing performance for solar light.

PMID- 29168004
TI  - Diffusion-weighted imaging of the prostate: should we use quantitative metrics to
      better characterize focal lesions originating in the peripheral zone?
AB  - PURPOSE: To compare inter-reader concordance and accuracy of qualitative
      diffusion-weighted (DW) PIRADSv2.0 score with those of quantitative DW-MRI for
      the diagnosis of peripheral zone prostate cancer. MATERIALS AND METHODS: Two
      radiologists independently assigned a DW-MRI-PIRADS score to 92 PZ-foci, in 74
      patients (64.3+/-5.6 years old; median PSA level: 8 ng/ml, normal DRE in 70 men).
      A standardised ADCmean and nine ADC-derived parameters were measured, including
      ADCratios with the whole-prostate (WP-ADCratio) or the mirror-PZ (mirror
      ADCratio) as reference areas. Surgical histology and MRI-TRUS fusion-biopsy were
      the reference for tumours and benign foci, respectively. Inter-reader agreement
      was assessed by the Cohen-kappa-coefficient and the intraclass correlation
      coefficient (ICC). Univariate-multivariate regressions determined the most
      predictive factor for cancer. RESULTS: Fifty lesions were malignant. Inter-reader
      concordance was fair for qualitative assessment, but excellent for quantitative
      assessment for all quantitative variables. At univariate analysis, ADCmean, WP
      ADCratio and WL-ADCmean performed equally, but significantly better than the
      mirror-ADCratio (p<0.001). At multivariate analysis, the only independent
      variable significantly associated with malignancy was the whole-prostate
      ADCratio. At a cut-off value of 0.68, sensitivity was 94-90 % and specificity was
      60-38 % for readers 1 and 2, respectively. CONCLUSION: The whole-prostate
      ADCratio improved the qualitative inter-reader concordance and characterisation
      of focal PZ-lesions. KEY POINTS: * Inter-reader concordance of DW PI-RADSv2.0
      score for PZ lesions was only fair. * Using a standardised ADCmean measurement
      and derived DW-quantitative parameters, concordance was excellent. * The whole
      prostate ADCratio performed significantly better than the mirror-ADCratio for
      cancer detection. * At a cut-off of 0.68, sensitivity values of WP-ADCratio were
      94-90 %. * The whole-prostate ADCratio may circumvent variations of ADC metrics
      across centres.

PMID- 29168005
TI  - A survey by the European Society of Breast Imaging on the utilisation of breast
      MRI in clinical practice.
AB  - OBJECTIVES: While magnetic resonance imaging (MRI) is considered a helpful
      diagnostic tool in breast imaging, discussions are ongoing about appropriate
      protocols and indications. The European Society of Breast Imaging (EUSOBI)
      launched a survey to evaluate the utilisation of breast MRI in clinical practice.
      METHODS: An online survey reviewed by the EUSOBI board and committees was
      distributed amongst members. The questions encompassed: training and experience;
      annual breast MRI and MRI-guided-intervention workload; examination protocols;
      indications; reporting habits and preferences. Data were summarised and subgroups
      compared using chi2 test. RESULTS: Of 647 EUSOBI members, 177 (27.4%) answered
      the survey. The majority were radiologists (90.5%), half of them based in
      academic centres (51.9%). Common indications for MRI included cancer staging,
      treatment monitoring, high-risk screening and problem-solving, and differed
      significantly between countries (p<=0.03). Structured reporting and BI-RADS were
      mostly used. Breast radiologists with <=10 years of experience preferred
      inclusion of additional techniques, such as T2/STIR (p=0.03) and DWI (p=0.08) in
      the scan protocol. MRI-guided interventions were performed by a minority of
      participants (35.4%). CONCLUSIONS: The utilisation of breast MRI in clinical
      practice is generally in line with international recommendations. There are
      substantial differences between countries. MRI-guided interventions and
      functional MRI parameters are not widely available. KEY POINTS: * MRI is commonly
      used for the detection and characterisation of breast lesions. * Clinical
      practice standards are generally in line with current recommendations. *
      Standardised criteria and diagnostic categories (mainly BI-RADS) are widely
      adopted. * Younger radiologists value additional techniques, such as T2/STIR and
      DWI. * MRI-guided breast biopsy is not widely available.

PMID- 29168006
TI  - Breast lesions classified as probably benign (BI-RADS 3) on magnetic resonance
      imaging: a systematic review and meta-analysis.
AB  - PURPOSE: To investigate prevalence, malignancy rates, imaging features, and
      follow-up intervals for probably benign (BI-RADS 3) lesions on breast magnetic
      resonance imaging (MRI). METHODS: A systematic database-review of articles
      published through 22/06/2016 was performed. Eligible studies reported BI-RADS 3
      lesions on breast MRI. Two independent reviewers performed a literature review
      and data extraction. Data collection included study characteristics, number/type
      of BI-RADS 3 lesions, final diagnosis (histopathology and/or follow-up). Sources
      of bias (QUADAS-2) were assessed. Meta-analysis included data-pooling,
      heterogeneity testing, and meta-regression. RESULTS: Fifteen studies were
      included. Prevalence was reported in 11 studies (range: 1.2-24.3%). Malignancy
      rates ranged between 0.5-10.1% (pooled 61/2814, 1.6%, 95%-CI:0.9-2.3% (random
      effects-model), I2=53%, P=0.007). In a subgroup of 11 studies (2183 lesions),
      highest malignancy rates were observed in non-mass lesions (pooled 25/714, 2.3%,
      95%-CI:0.8-3.9%, I2=52%, P=0.021) followed by mass lesions (pooled 15/771, 1.5%,
      95%-CI:0.7-2.4%, I2=0%, P=0.929), and foci (pooled 10/698, 1%, 95%-CI:0.3-1.7%,
      I2=0%, P=0.800). There was non-significant negative association between
      prevalence and malignancy rates (P=0.077). Malignant lesions were diagnosed at
      all follow-up time points. CONCLUSION: While prevalence of MRI BI-RADS 3 lesions
      was strongly heterogeneous, pooled malignancy rates met BI-RADS benchmarks (<2%).
      Malignancy rates varied, exceeding 2% in non-mass lesions. Twenty-four-month
      surveillance is required to detect all malignant lesions. KEY POINTS: * Probably
      benign (BI-RADS 3) lesions showed a pooled malignancy-rate of 1.6% (95%-CI:0.9
      2.3%). * Malignancy rates differ and are highest in non-mass lesions (2.3%, 95%
      CI:0.8-3.9%). * The prevalence of BI-RADS 3 lesions on breast MRI ranged from 1.2
      24.3%. * Malignant lesions were diagnosed at follow-up time points up to 24
      months.

PMID- 29168007
TI  - Can dual-energy CT replace perfusion CT for the functional evaluation of advanced
      hepatocellular carcinoma?
AB  - OBJECTIVES: To determine the degree of relationship between iodine concentrations
      derived from dual-energy CT (DECT) and perfusion CT parameters in patients with
      advanced HCC under treatment. METHODS: In this single-centre IRB approved study,
      16 patients with advanced HCC treated with sorafenib or radioembolization who
      underwent concurrent dynamic perfusion CT and multiphase DECT using a single
      source, fast kV switching DECT scanner were included. Written informed consent
      was obtained for all patients. HCC late-arterial and portal iodine
      concentrations, blood flow (BF)-related and blood volume (BV)-related perfusion
      parameters maps were calculated. Mixed-effects models of the relationship between
      iodine concentrations and perfusion parameters were computed. An adjusted p value
      (Bonferroni method) < 0.05 was considered significant. RESULTS: Mean HCC late
      arterial and portal iodine concentrations were 22.7+/-12.7 mg/mL and 18.7+/-8.3
      mg/mL, respectively. Late-arterial iodine concentration was significantly related
      to BV (mixed-effects model F statistic (F)=28.52, p<0.0001), arterial BF (aBF,
      F=17.62, p<0.0001), hepatic perfusion index (F=28.24, p<0.0001), positive
      enhancement integral (PEI, F=66.75, p<0.0001) and mean slope of increase
      (F=32.96, p<0.0001), while portal-venous iodine concentration was mainly related
      to BV (F=29.68, p<0.0001) and PEI (F=66.75, p<0.0001). CONCLUSIONS: In advanced
      HCC lesions, DECT-derived late-arterial iodine concentration is strongly related
      to both aBF and BV, while portal iodine concentration mainly reflects BV,
      offering DECT the ability to evaluate both morphological and perfusion changes.
      KEY POINTS: * Late-arterial iodine concentration is highly related to arterial BF
      and BV. * Portal iodine concentration mainly reflects tumour blood volume. * Dual
      energy CT offers significantly decreased radiation dose compared with perfusion
      CT.

PMID- 29168009
TI  - Dietary lipophilic iron accelerates regional brain iron-load in C57BL6 mice.
AB  - Impaired brain iron homeostatic mechanisms, independent of pathological
      hallmarks, are harmful to the brain because excess free iron can cause DNA,
      protein, and lipid damage via oxidative stress. The goal of this study was to
      evaluate the longitudinal effect of chronic iron overload and deficiency in the
      vertebrate brain. Ten-week-old C57BL6 male mice were randomly assigned to one of
      four unique dietary regiments for 1 year: iron-deficient, normal iron, and two
      different concentrations of lipophilic iron diet containing 3,5,5
      trimethylhexanoyl ferrocene (TMHF). Longitudinal MRI parametrics were used to
      assess the location and extent of ferric iron distribution. Tissue collected at
      12 months was used to directly measure iron-load, protein alterations, and
      histological metrics. While the iron-deficient diet did not alter brain iron
      stores, 0.11% TMHF and early exposure with 0.5% TMHF elevated brain iron by
      roughly 40 and 100%, respectively. R 2 rate increased more in the TMHF groups
      within iron rich brain regions. Increased brain iron concentration was linearly
      correlated with an increase in L-ferritin expression, and TMHF diet was found to
      increase L-ferritin within the olfactory bulb, neocortex, pallidum, thalamus,
      corpus callosum, CA3 regions of the hippocampus, and substantia nigra. Moreover,
      gliosis and oxidative stress were detected in the TMHF groups in the regions
      associated with iron-load. Spatial memory impairment was evident in the iron
      loaded mice. This work illustrates that lipophilic iron elevates brain iron in a
      regionally specific fashion and positions dietary TMHF administration as a model
      for brain iron overloading.

PMID- 29168008
TI  - GABAA receptor subunit deregulation in the hippocampus of human foetuses with
      Down syndrome.
AB  - The function, regulation and cellular distribution of GABAA receptor subunits
      have been extensively documented in the adult rodent brain and are linked to
      numerous neurological disorders. However, there is a surprising lack of knowledge
      on the cellular (sub-) distribution of GABAA receptor subunits and of their
      expressional regulation in developing healthy and diseased foetal human brains.
      To propose a role for GABAA receptor subunits in neurodevelopmental disorders, we
      studied the developing hippocampus of normal and Down syndrome foetuses. Among
      the alpha1-3 and gamma2 subunits probed, we find significantly altered expression
      profiles of the alpha1, alpha3 and gamma2 subunits in developing Down syndrome
      hippocampi, with the alpha3 subunit being most affected. alpha3 subunits were
      selectively down-regulated in all hippocampal subfields and developmental periods
      tested in Down syndrome foetuses, presenting a developmental mismatch by their
      adult-like distribution in early foetal development. We hypothesized that
      increased levels of the amyloid precursor protein (APP), and particularly its
      neurotoxic beta-amyloid (1-42) fragment, could disrupt alpha3 gene expression,
      likely by facilitating premature neuronal differentiation. Indeed, we find
      increased APP content in the hippocampi of the Down foetuses. In a corresponding
      cellular model, soluble beta-amyloid (1-42) administered to cultured SH-SY5Y
      neuroblastoma cells, augmented by retinoic acid-induced differentiation towards a
      neuronal phenotype, displayed a reduction in alpha3 subunit levels. In sum, this
      study charts a comprehensive regional and subcellular map of key GABAA receptor
      subunits in identified neuronal populations in the hippocampus of healthy and
      Down syndrome foetuses and associates increased beta-amyloid load with discordant
      down-regulation of alpha3 subunits.

PMID- 29168011
TI  - Pediatric prolactinoma: initial presentation, treatment, and long-term prognosis.
AB  - : Prolactinoma is a rare pituitary adenoma secreting prolactin. Studies on
      diagnostics, treatment, and prognosis in pediatric prolactinoma patients are
      rare. We analyzed clinical presentation, response to treatment, and prognosis of
      27 pediatric prolactinoma patients (10 m/17 f. based on patients' records. Tumors
      included 6 microadenomas (tumor volume: median 0.2 cm3, range 0.01-0.4 cm3; serum
      prolactin at diagnosis: median 101 ng/ml, range 33-177 ng/ml), 15 macroadenomas
      (volume: median 3.3 cm3, range 0.4-25.8 cm3; prolactin: median 890 ng/ml, range
      87-8624), and 3 giant adenomas (volume: median 44.5 cm3, range 38.6-93.5 cm3;
      prolactin: median 4720 ng/ml, range 317-10,400); data for 3 patients were not
      available. Dopamine agonist treatment (n = 22) was safe and effective, leading to
      reductions in tumor size (p < 0.01) and prolactin levels (p < 0.01). Threat to
      vision was the indication for decompressing surgery in three of seven operated
      patients. No patient was irradiated. Long-term functional capacity was not
      impaired when compared with other sellar masses (n = 235). CONCLUSION: In
      pediatric prolactinoma, diagnosis is based on hyperprolactinemia and imaging.
      Dopamine agonist treatment is effective and safe. Overall survival and functional
      capacity as a measure of quality of survival were not impaired, indicating an
      optimistic prognosis. Surgery should be considered only in emergency situations
      of threatened visual function, not presenting a fast response to dopamine agonist
      treatment. Severe side effects of medication and lack of efficacy should be
      considered as contraindications. What is Known: * In pediatric prolactinoma-a
      very rare pediatric neuroendocrinological disease-gender-related differences in
      terms of clinical presentation at initial diagnosis are known. * Due to the
      rareness of the disease, reports on long-term outcome and prognosis after
      childhood-onset prolactinoma based on prospective follow-up are not published.
      What is New: * Dopamine agonist treatment is efficient and safe for tumor volume
      reduction in pediatric prolactinoma and surgical interventions are recommended
      only for decompression of the optic chiasm in case of threat to vision. In case
      of inefficient response to medication, side effects or parental refuse,
      alternative therapeutic options should be considered. * Quality of life in terms
      of survival and functional capacity was not impaired in pediatric prolactinoma
      patients when compared with 235 long-term survivors of different sellar masses.

PMID- 29168010
TI  - Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for
      HCN channels.
AB  - Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have
      important functions in controlling neuronal excitability and generating rhythmic
      oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b
      interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward
      current, I h, in the thalamocortical system and its functional relevance for the
      physiological thalamocortical oscillations were investigated. A significant
      decrease in I h current density, in both thalamocortical relay (TC) and cortical
      pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b-/-). In addition
      basal cAMP levels in the brain were found to be decreased while the availability
      of the fast transient A-type K+ current, I A, in TC neurons was increased. These
      changes were associated with alterations in intrinsic properties and firing
      patterns of TC neurons, as well as intrathalamic and thalamocortical network
      oscillations, revealing a significant increase in slow oscillations in the delta
      frequency range (0.5-4 Hz) during episodes of active-wakefulness. In addition,
      absence of TRIP8b suppresses the normal desynchronization response of the EEG
      during the switch from slow-wave sleep to wakefulness. It is concluded that
      TRIP8b is necessary for the modulation of physiological thalamocortical
      oscillations due to its direct effect on HCN channel expression in thalamus and
      cortex and that mechanisms related to reduced cAMP signaling may contribute to
      the present findings.

PMID- 29168012
TI  - Cost-effectiveness of rule-based immunoprophylaxis against respiratory syncytial
      virus infections in preterm infants.
AB  - : The objective of the paper is to assess the cost-effectiveness of targeted
      respiratory syncytial virus (RSV) prophylaxis based on a validated prediction
      rule with 1-year time horizon in moderately preterm infants compared to no
      prophylaxis. Data on health care consumption were derived from a randomised
      clinical trial on wheeze reduction following RSV prophylaxis and a large birth
      cohort study on risk prediction of RSV hospitalisation. We calculated the
      incremental cost-effectiveness ratio (ICER) of targeted RSV prophylaxis vs. no
      prophylaxis per quality-adjusted life year (QALYs) using a societal perspective,
      including medical and parental costs and effects. Costs and health outcomes were
      modelled in a decision tree analysis with sensitivity analyses. Targeted RSV
      prophylaxis in infants with a first-year RSV hospitalisation risk of > 10%
      resulted in a QALY gain of 0.02 (0.931 vs. 0.929) per patient against additional
      cost of ?472 compared to no prophylaxis (ICER ?214,748/QALY). The ICER falls
      below a threshold of ?80,000 per QALY when RSV prophylaxis cost would be lowered
      from ?928 (baseline) to ?406 per unit. At a unit cost of ?97, RSV prophylaxis
      would be cost saving. CONCLUSIONS: Targeted RSV prophylaxis is not cost-effective
      in reducing RSV burden of disease in moderately preterm infants, but it can
      become cost-effective if lower priced biosimilar palivizumab or a vaccine would
      be available.

PMID- 29168013
TI  - Clinical features and treatment of pediatric patients with drug-induced
      anaphylaxis: a study based on pharmacovigilance data.
AB  - : We assessed the clinical features and treatment of pediatric patients with drug
      induced anaphylaxis in clinical settings. Pediatric drug-induced anaphylaxis
      cases collected by the Beijing Pharmacovigilance Database from 2004 to 2014 were
      analyzed. A total of 91 cases were identified. Drug-induced anaphylaxis was
      primarily caused by antibiotics (53%). Children of 0-5 years were more likely to
      develop cyanosis symptoms than children of 13-17 years (OR = 5.14, 95%CI [1.74,
      15.20], P = 0.002). Children of 13-17 years were more likely to develop
      hypotension than children of 6-12 years (OR = 11.79, 95%CI [2.28, 60.87], P =
      0.002), and to manifest both neurological symptoms (OR = 3.56, 95%CI [1.26,
      10.08], P = 0.015) and severe anaphylaxis than children of 0-5 years (OR = 15.46,
      95%CI [1.85, 129.33], P = 0.002). Supratherapeutic doses of epinephrine were more
      likely with intravenous (IV) bolus (92%) in contrast to either intramuscular (IM)
      (36%, OR = 19.25, 95%CI [1.77, 209.55], P = 0.009) or subcutaneous (SC)
      injections (36%, OR = 19.80, 95% CI [1.94, 201.63], P = 0.005). Only 62 (68%)
      patients received epinephrine treatment as the first-line therapy. CONCLUSION:
      This study demonstrates that antibiotics were the most common cause of pediatric
      drug-induced anaphylaxis. Children may present with different anaphylactic
      signs/symptoms based on age groups. Epinephrine is under-utilized and provider
      education on the proper management of drug-induced anaphylaxis is warranted. What
      is Known: * The most common causes of anaphylaxis in children are allergies to
      foods. Drugs are the second most common cause of pediatric anaphylaxis. * IM
      epinephrine is the recommended initial treatment of anaphylaxis. What is New: *
      Drug-induced anaphylaxis in pediatric patients has age-related clinical features.
      * IV bolus epinephrine was overused and associated with supratherapeutic dosing.

PMID- 29168014
TI  - Myocardial perfusion reserve quantified by cardiac magnetic resonance imaging is
      associated with late gadolinium enhancement in hypertrophic cardiomyopathy.
AB  - Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging
      has demonstrated the capability of stratifying hypertrophic cardiomyopathy (HCM).
      Stress perfusion test of CMR can quantify myocardial perfusion reserve (MPR), but
      its clinical role is not determined. The purpose of this study was to investigate
      the relationship between MPR and LGE in patients with HCM. A total of 61
      consecutive cases underwent complete evaluation with electrocardiography and CMR
      [cine imaging, coronary MR angiography (MRA), and stress perfusion testing with
      LGE]. HCM cases were diagnosed by the Japanese conventional guideline prior to
      this CMR study. Mild LVH was defined as more than 13 mm in maximum LV wall
      thickness at end diastole on the cine imaging of the CMR. MPR was calculated as
      the ratio of stress/rest myocardial blood flow using an intensity curve on the
      stress perfusion test. Cases with ischemic heart disease were excluded from the
      study based on clinical history and coronary MRA. There were 37 HCM and 24 mild
      LVH cases (average age: 60.5 +/- 10.9 vs. 64.8 +/- 10.8; male: 62.2 vs. 75.0%,
      respectively, non-significant). MPR in HCM was lower than in LVH (1.5 +/- 0.5 vs.
      2.2 +/- 0.9, p < 0.001) and normal subjects (2.4 +/- 0.9, p < 0.001). MPR in HCM
      with LGE (N = 34) was lower than in HCM without LGE (N = 3) (1.4 +/- 0.5 vs. 2.1
      +/- 0.2, p = 0.014). Multiple regression analysis verified that LGE was the
      strongest predictor of MPR among multiple clinical parameters, including LVH, LV
      dysfunction (ejection fraction < 50%), and the presence of negative T wave (p <
      0.001). MPR was impaired in HCM with LGE compared with HCM without LGE. The
      clinical role of MPR on CMR needs to be clarified by further research.

PMID- 29168016
TI  - Qualitative Evaluation of a Peer Navigator Program for Latinos with Serious
      Mental Illness.
AB  - Peer navigator programs (PNP) may help reduce physical health disparities for
      ethnic minorities with serious mental illness (SMI). However, specific aspects of
      PNP that are important to peer navigators and their clients are under-researched.
      A qualitative study explored the perspectives of service users (n = 15) and peer
      navigators (n = 5) participating in a randomized controlled trial of a PNP for
      Latinos with SMI. Results show PN engagement with service users spans diverse
      areas and that interactions with peers, trust, and accessibility are important
      from a service user perspective. PNs discussed needs for high-quality
      supervision, organizational support, and additional resources for undocumented
      Latinos.

PMID- 29168015
TI  - Ascending aortic blood flow velocity is increased in children with primary
      snoring/mild sleep-disordered breathing and associated with an increase in CD8 + 
      T cells expressing TNFalpha and IFNgamma.
AB  - Sleep-disordered breathing (SDB) is associated with cardiovascular disease and
      systemic inflammation in adults but this remains to be explored in children,
      especially in children with the most common form of SDB, i.e. primary
      snoring/mild SDB. This pilot study investigated the relationship between the
      cardiovascular function and inflammation in children with mild SDB. Nineteen
      participants aged 5-14 years underwent overnight polysomnography, cardiac
      magnetic resonance imaging (aortic blood flow velocity and left and right
      ventricular systolic function) and assessment for inflammatory markers
      (intracellular cytokine analysis of T cells by flow cytometry). Parents also
      completed the Sleep Disturbances Scale for Children (SDSC). Children with mild
      SDB exhibited increased ascending aortic peak systolic velocity compared to
      controls (SDB 119.95 m/s vs. control 101.49 m/s, p < 0.05). No significant group
      differences were observed for left and right ventricular ejection fraction or
      mean aortic blood flow velocity from either the ascending aorta or pulmonary
      artery. Children with mild SDB had increased inflammatory markers as demonstrated
      by elevated T cell interferon gamma (IFNgamma) (SDB 52 +/- 4% vs. control 25 +/-
      3% positive cells, p < 0.005) and tumour necrosis factor alpha (TNFalpha) (SDB 39
      +/- 4% vs. control 20 +/- 2% positive cells, p < 0.005) expression from CD8+
      cells. A strong positive correlation was observed between ascending aorta peak
      blood flow velocity and both TNFalpha and IFNgamma (TNFalpha, r = 0.54, p < 0.03;
      IFNgamma, r = 0.63, p < 0.005, respectively). Polysomnography revealed that
      oxygen saturation (SaO2) nadir was significantly lower in children with mild SDB
      compared to controls (SDB 92.3 +/- 2.7% vs. control 94.4 +/- 1.6%, p < 0.05). A
      lower SaO2 nadir was associated with an increased ascending aorta peak systolic
      velocity (r = - 0.48, p < 0.05). As well, both a lower SaO2 nadir and an
      increased ascending aorta peak systolic velocity were associated with higher SDSC
      Sleep-Disordered Breathing and Disorder of Initiating and Maintaining Sleep
      subscale scores but not the polysomnographic-derived Obstructive Apnea-Hypopnea
      Index. The finding of elevated ascending aortic peak systolic blood flow velocity
      and its association with increased inflammatory markers suggests that the profile
      of cardiovascular changes noted in adult SDB may also occur in children with mild
      SDB.

PMID- 29168017
TI  - A Comparative Study of the Robustness of Frequency-Domain Connectivity Measures
      to Finite Data Length.
AB  - In this work we use numerical simulation to investigate how the temporal length
      of the data affects the reliability of the estimates of brain connectivity from
      EEG time-series. We assume that the neural sources follow a stable MultiVariate
      AutoRegressive model, and consider three connectivity metrics: imaginary part of
      coherency (IC), generalized partial directed coherence (gPDC) and frequency
      domain granger causality (fGC). In order to assess the statistical significance
      of the estimated values, we use the surrogate data test by generating phase
      randomized and autoregressive surrogate data. We first consider the ideal case
      where we know the source time courses exactly. Here we show how, expectedly, even
      exact knowledge of the source time courses is not sufficient to provide reliable
      estimates of the connectivity when the number of samples gets small; however,
      while gPDC and fGC tend to provide a larger number of false positives, the IC
      becomes less sensitive to the presence of connectivity. Then we proceed with more
      realistic simulations, where the source time courses are estimated using eLORETA,
      and the EEG signal is affected by biological noise of increasing intensity. Using
      the ideal case as a reference, we show that the impact of biological noise on IC
      estimates is qualitatively different from the impact on gPDC and fGC.

PMID- 29168018
TI  - A Robotic Flexible Drill and Its Navigation System for Total Hip Arthroplasty.
AB  - This paper presents a robotic flexible drill and its navigation system for total
      hip arthroplasty (THA). The new robotic system provides an unprecedented and
      unique capability to perform curved femoral milling under the guidance of a
      multimodality navigation system. The robotic system consists of three components.
      Firstly, a flexible drill manipulator comprises multiple rigid segments that act
      as a sheath to a flexible shaft with a drill/burr attached to the end. The second
      part of the robotic system is a hybrid tracking system that consists of an
      optical tracking system and a position tracking system. Optical tracking units
      are used to track the surgical objects and tools outside the drilling area, while
      a rotary encoder placed at each joint of the sheath is synchronized to provide
      the position information for the flexible manipulator with its virtual object.
      Finally, the flexible drill is integrated into a computer-aided navigation
      system. The navigation system provides real time guidance to a surgeon during the
      procedure. The flexible drill system is then able to implement THA by bone
      milling. The final section of this paper is an evaluation of the flexible and
      steerable drill and its navigation system for femoral bone milling in sawbones.

PMID- 29168019
TI  - The operations of the free maternal care policy and out of pocket payments during
      childbirth in rural Northern Ghana.
AB  - BACKGROUND: To promote skilled attendance at births and reduce maternal deaths,
      the government of Ghana introduced the free maternal care policy under the
      National Health Insurance Scheme (NHIS) in 2008. The objective is to eliminate
      financial barriers associated with the use of services. But studies elsewhere
      showed that out of pocket (OOP) payments still exist in the midst of fee
      exemptions. The aim of this study was to estimate OOP payments and the financial
      impact on women during childbirth in one rural and poor area of Northern Ghana;
      the Kassena-Nankana municipality. Costs were taken from the perspective of women.
      METHODS: Quantitative and qualitative data collection techniques were used in a
      convergent parallel mixed methods study. The study used structured questionnaire
      (n = 353) and focus group discussions (FGDs =7) to collect data from women who
      gave birth in health facilities. Quantitative data from the questionnaire were
      analysed, using descriptive statistics. Qualitative data from the FGDs were
      recorded, transcribed and analysed to determine common themes. RESULTS: The
      overall mean OOP payments during childbirth was GHc33.50 (US$17), constituting
      5.6% of the average monthly household income. Over one-third (36%, n = 145) of
      women incurred OOP payments which exceeded 10% of average monthly household
      income (potentially catastrophic). Sixty-nine percent (n = 245) of the women
      perceived that the NHIS did not cover all expenses incurred during childbirth;
      which was confirmed in the FGDs. Both survey and FGDs demonstrated that women
      made OOP payments for drugs and other supplies. The FGDs showed women bought
      disinfectants, soaps, rubber pads and clothing for newborns as well. Seventy-five
      percent (n = 264) of the women used savings, but 19% had to sell assets to
      finance the payments; this was supported in the FGDs. CONCLUSION: The NHIS policy
      has not eliminated financial barriers associated with childbirth which impacts
      the welfare of some women. Women continued to make OOP payments, largely as a
      result of a delay in reimbursement by the NHIS. There is need to re-examine the
      reimbursement system in order to prevent shortage of funding to health facilities
      and thus encourage skilled attendance for the reduction of maternal deaths as
      well as the achievement of universal health coverage.

PMID- 29168020
TI  - Copper chaperone antioxidant-1, Atox-1, is involved in the induction of SOD3 in
      THP-1 cells.
AB  - Superoxide dismutase (SOD) 3, a copper (Cu)-containing anti-oxidative enzyme,
      plays a key role in extracellular redox homeostasis. Cu chaperone antioxidant-1
      (Atox-1) not only delivers Cu ions to SOD3 at the trans-Golgi network, it also
      functions as a transcription factor of SOD3; however, the role of Atox-1 in the
      regulation of SOD3 during the monocytic differentiation of THP-1 cells has not
      yet been elucidated. A treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced the expression of the Cu transport protein ATP7A in THP-1 cells. On the
      other hand, the nuclear translocation of Atox-1 was detected in TPA-treated THP-1
      cells, and was suppressed in the presence of the Cu chelator,
      bathocuproinedisulfonic acid. Furthermore, Atox-1 bound to the SOD3 promoter
      region in TPA-treated THP-1 cells. The overexpression of Atox-1 in THP-1 cells
      significantly enhanced TPA-elicited SOD3 expression, whereas its knockdown
      suppressed this induction. The present results demonstrate that Atox-1 functions
      as a key molecule in TPA-elicited SOD3 expression.

PMID- 29168021
TI  - Application of methyl-TROSY to a large paramagnetic membrane protein without
      perdeuteration: 13C-MMTS-labeled NADPH-cytochrome P450 oxidoreductase.
AB  - NMR spectroscopy of membrane proteins involved in electron transport is difficult
      due to the presence of both the lipids and paramagnetic centers. Here we report
      the solution NMR study of the NADPH-cytochrome P450 oxidoreductase (POR) in its
      reduced and oxidized states. We interrogate POR, first, in its truncated soluble
      form (70 kDa), which is followed by experiments with the full-length protein
      incorporated in a lipid nanodisc (240 kDa). To overcome paramagnetic relaxation
      in the reduced state of POR as well as the signal broadening due to its high
      molecular weight, we utilized the methyl-TROSY approach. Extrinsic 13C-methyl
      groups were introduced by modifying the engineered surface-exposed cysteines with
      methyl-methanethiosulfonate. Chemical shift dispersion of the resonances from
      different sites in POR was sufficient to monitor differential effects of the
      reduction-oxidation process and conformation changes in the POR structure related
      to its function. Despite the high molecular weight of the POR-nanodisc complex,
      the surface-localized 13C-methyl probes were sufficiently mobile to allow for
      signal detection at 600 MHz without perdeuteration. This work demonstrates a
      potential of the solution methyl-TROSY in analysis of structure, dynamics, and
      function of POR, which may also be applicable to similar paramagnetic and
      flexible membrane proteins.

PMID- 29168022
TI  - No advantage of fresh blastocyst versus cleavage stage embryo transfer in women
      under the age of 39: a randomized controlled study.
AB  - PURPOSE: Is there a difference in implantation and pregnancy rates between
      embryos transferred electively at cleavage or blastocyst stage in infertile women
      <= 38 years with at least four zygotes on day 1 post retrieval? METHODS: A
      randomized clinical trial was conducted in a single tertiary care hospital with a
      sample size of 194 patients in each arm for a total population of 388 women.
      Patients less than 39 years of age with more than three fertilized oocytes and
      less than four previous assisted reproductive technology (ART) attempts were
      inclusion criteria. RESULTS: The two groups were similar for age, years of
      infertility, indication to treatment, basal antimullerian hormone and FSH, number
      of previous ART cycles, primary or secondary infertility, type of induction
      protocol, days of stimulation, total gonadotrophin dose, and estradiol (E2) and
      progesterone (P) levels at trigger. No statistically significant differences were
      found in terms of number of retrieved oocytes, inseminated oocytes, fertilization
      rate, canceled transfers (7.73% in blastocyst and 3.61% in cleavage stage group),
      and cycles with frozen embryos and/or oocytes. Although a higher number of
      fertilized oocytes were in the blastocyst stage group (6.18 +/- 1.46 vs 5.89 +/-
      1.54, p = 0.052), a statistically greater number of embryos/randomized cycle were
      transferred at cleavage stage (1.93 +/- 0.371) compared with the number of
      transferred blastocysts (1.80 +/- 0.56), probably due to the number of embryos
      not reaching blastocyst stage (3.09%). The implantation rate (28.37 vs 25.67%),
      pregnancy rate per cycle (36.06 vs38.66%), transfer (39.66 vs 40.11%),
      spontaneous abortions (19.72% vs 12.00%), delivery rate per cycle (27.84 vs
      32.99%), and transfer (30.17 vs 34.22%) were not significantly different between
      the blastocyst and cleavage stage groups. The twin delivery rate was higher in
      the blastocyst stage group, although not significant (42.59 vs 28.12%). The mean
      numbers of frozen blastocyst (2.30 +/- 1.40 vs 2.02 +/- 1.00) and frozen oocytes
      (7.09 +/- 3.55vs 6.79 +/- 3.26) were not significantly different between the two
      groups. CONCLUSIONS: Fresh blastocyst-stage transfer versus cleavage-stage
      transfer did not show any significant difference in terms of implantation and
      pregnancy rate in this selected group of patients. A high twin delivery rate in
      both groups (35.59%) was registered, and although not significant, they were
      higher in the blastocyst transfer group (42.59 vs 28.12%). Our conclusion
      supports considering single embryo transfer (SET) policy, even in cleavage stage
      in patients younger than 39 years with at least four zygotes. TRIAL REGISTRATION:
      ClinicalTrials.gov registration number NCT02639000.

PMID- 29168023
TI  - Oxytocin and parenting behavior among impoverished mothers with low vs. high
      early life stress.
AB  - Recent work suggests that key aspects of sensitive parenting (e.g., warmth,
      emotional attunement) may be shaped in part by biology, specifically the
      neuropeptide oxytocin. However, some studies have found that oxytocin may not act
      in expected ways in higher-risk populations (e.g., those with postnatal
      depression or borderline personality disorder). This study examined the relation
      between oxytocin and parenting among mothers with varying levels of early life
      stress. Forty low-income mothers and their 34- to 48-month-old child participated
      in this study. Mother-child dyads were observed in an interaction task in their
      home, and videos of these interactions were later coded for parenting behaviors.
      Mothers' oxytocin production before and after the interaction task was assessed
      through saliva. Mothers' early stress was assessed via the Adverse Childhood
      Experiences Scale (ACES; Felitti et al. Am J Prev Med 14:245-258, 1998). For
      mothers with low ACEs, higher oxytocin secretion was associated with more
      positive parenting. For mothers with high ACEs, higher oxytocin secretion was
      associated with lower levels of positive parenting. Oxytocin may be operating
      differently for mothers who experienced harsh early social environments,
      supporting more defensive behaviors and harsh parenting than anxiolytic and
      prosocial behaviors.

PMID- 29168024
TI  - Teenage pregnancy and long-term mental health outcomes among Indigenous women in
      Canada.
AB  - Our objectives were to (1) compare the risks for poor long-term mental health
      outcomes among indigenous women with and without a teenage pregnancy and (2)
      determine if community and cultural factors modify this risk. We conducted a
      secondary analysis of the 2012 Aboriginal Peoples Survey. Respondents were women
      aged 25 to 49 years who had given birth to at least one child. Teenage mothers
      (age at first birth 13 to 19 years; n = 1330) were compared to adult mothers (age
      at first birth 20 years or older; n = 2630). Mental health outcomes were
      psychological distress, mental health status, suicide ideation/attempt, and
      alcohol consumption. To address objective 1, we used binary logistic regression
      analyses before and after controlling for covariates. To address objective 2, we
      tested the significance of interaction terms between teenage pregnancy status and
      effect measure modifiers. In unadjusted analyses, teenage pregnancy was
      associated with increased risk for poor/fair mental health [odds ratio (OR) 1.77,
      95% confidence interval (CI) 1.24-2.53] and suicide attempt/ideation (OR 1.95,
      95% CI 1.07-3.54). However, the associations were not statistically significant
      after adjusting for demographic, socioeconomic, environmental, and health
      covariates. Teenage pregnancy was not associated with increased risk for high
      psychological distress or heavy alcohol consumption in unadjusted or adjusted
      analyses. The interaction term for involvement in cultural activities was
      statistically significant for poor/fair mental health; however, after
      stratification, ORs were non-significant. Among indigenous mothers, teenage
      pregnancy was less important than broader social and health circumstances in
      predicting long-term mental health.

PMID- 29168025
TI  - Relationship between the severity of laryngopharyngeal reflux and sleep apnea:
      using drug-induced sleep endoscopy (DISE).
AB  - OBJECTIVES: The aim of the study is to identify the following associations: (1)
      severity of obstructive sleep apnea syndrome (OSAS) and laryngopharyngeal reflux
      (LPR)-related clinical parameters, such as reflux finding score (RFS), reflux
      symptom index (RSI), and LPR-health-related quality of life (LPR-HRQOL) and (2)
      complete obstruction on drug-induced sleep endoscopy (DISE) and LPR-related
      clinical parameters. MATERIALS AND METHODS: Subjects included the OSAS patients
      without surgery history and all patients perform the polysomnography (PSG) and
      DISE for their OSAS. Demographics, polysomnographic data, DISE results, and LPR
      related parameters were collected prospectively. The patients were divided into
      age-, sex-, and BMI-matched two groups, according to numbers of complete
      obstruction on DISE (complete obstruction at 0-1 subsites (unilevel) vs. 2-4
      subsites (multilevel). Finally, 19 patients with unilevel complete obstruction
      and 38 patients with multilevel complete obstruction were compared. The multiple
      linear regression analysis was employed to determine the predictors of LPR
      related quality of life. RESULTS: Among 88 patients, 19 patients demonstrated
      unilevel complete obstruction, and 69 patients demonstrated multilevel complete
      obstruction on DISE. There were no significant correlation between OSAS severity
      and RFS, RSI, and scores of LPR-HRQOL. Multilevel complete obstruction on DISE
      did not affect the LPR-related clinical parameters (p > 0.05). The result of
      multiple linear regression demonstrated complete obstruction at the epiglottis
      had a strong influence on the high scores of LPR-HRQOL. CONCLUSION: LPR is
      commonly developing disease with OSAS, but the OSAS severity did not affect the
      LPR-related parameters. The multilevel complete obstruction on DISE was not
      associated with the LPR-related clinical parameters.

PMID- 29168026
TI  - Author's reply to "Letter to the editor on the article: Saccular measurements in
      routine MRI can predict hydrops in Meniere's disease by Simon F et al."
AB  - This is an answer to the Letter to the Editor regarding our previously published
      article " Saccular measurements in routine MRI can predict hydrops in Meniere's
      disease ". We thank the authors for their interest in our article and their
      insightful comments. We would like to emphasise that our article was a
      preliminary study and to our knowledge the first published series establishing a
      correlation between measurements of saccular morphology in T2-weighed 3D CISS
      images and clinical definite Meniere's disease. Therefore, we agree with the
      authors of the Letter that verifying reproducibility is paramount for the
      technique to be widely used. Further studies should be conducted to investigate
      the risk of artefacts reducing the reliability of saccular width measurements and
      to confirm the clinical implications. We recommend the use of saccular height
      measurements which have higher reliability. Also, the goal of the study was to
      present a possible radiological alternative to the more established methods of
      endolymphatic hydrops visualisation. If accessible, we agree that the latter
      techniques should be preferred, but we find that they are unfortunately too often
      unavailable in routine clinical practice to ENT physicians.

PMID- 29168027
TI  - Combined microscopic/endoscopic management of petrous apex lesions.

PMID- 29168028
TI  - Systemic, intratympanic and combined administration of steroids for sudden
      hearing loss. A prospective randomized multicenter trial.
AB  - PURPOSE: The purpose of this prospective, randomized, multicenter clinical trial
      was to compare the therapeutic efficacy of systemic versus intratympanic versus
      combined administration of steroids in the treatment of idiopathic sudden
      sensorineural hearing loss. METHODS: 102 patients with an up to 14 days history
      of idiopathic sudden sensorineural hearing loss were randomized to 1 of 3 arms
      and followed prospectively. Group A (35 patients) received prednisolone
      intravenously followed by methylprednisolone orally, whereas Group B (34
      patients) were administered intratympanic methylprednisolone. Patients in Group C
      (33 patients) were administered the combination of the above-mentioned treatment
      modalities. The patients were followed-up with pure tone audiograms on days 1
      (initiation of treatment), 3, 5, 10, 30 and 90. RESULTS: The final mean hearing
      gain was 29.0 dB HL for Group A, 27.0 dB HL for Group B and 29.8 dB HL for Group
      C. The differences between the three groups were not statistically significant.
      When hearing improvement was assessed according to Siegel's criteria, no
      statistically significant difference was recorded either. Furthermore, patients
      younger than 60 years old achieved significantly better hearing outcomes.
      CONCLUSIONS: The results demonstrated that systemic, intratympanic and combined
      steroid administration have similar results in the primary treatment of
      idiopathic sudden hearing loss. Younger patients are more likely to achieve
      better hearing outcomes.

PMID- 29168030
TI  - The Assessment of Competency in Thoracic Sonography (ACTS) scale: validation of a
      tool for point-of-care ultrasound.
AB  - BACKGROUND: The rapid adoption of point-of-care ultrasound (POCUS) has created a
      need to develop assessment tools to ensure that learners can competently use
      these technologies. In this study, the authors developed and tested a rating
      scale to assess the quality of point-of-care thoracic ultrasound studies
      performed by novices. In Phase 1, the Assessment of Competency in Thoracic
      Sonography (ACTS) scale was developed based on structured interviews with subject
      matter experts. The tool was then piloted on a small series of ultrasound studies
      in Phase 2. In Phase 3 the tool was applied to a sample of 150 POCUS studies
      performed by ten learners; performance was then assessed by two independent
      raters. RESULTS: Evidence for the content validity of the ACTS scale was provided
      by a consensus exercise wherein experts agreed on the general principles and
      specific items that make up the scale. The tool demonstrated reasonable inter
      rater reliability despite minimal requirements for evaluator training and
      displayed evidence of good internal structure, with related scale items
      correlating well with each other. Analysis of the aggregate learning curves
      suggested a rapid early improvement in learner performance with slower
      improvement after approximately 25-30 studies. CONCLUSIONS: The ACTS scale
      provides a straightforward means to assess learner performance. Our results
      support the conclusion that the tool is an effective means of making valid
      judgments regarding competency in point-of-care thoracic ultrasound, and that the
      majority of learner improvement occurs during their first 25-30 practice studies.

PMID- 29168029
TI  - The Chinese version of the SLEQOL is a reliable assessment of health-related
      quality of life in Han Chinese patients with systemic lupus erythematosus.
AB  - To assess the health-related quality of life (HRQOL) of Han Chinese people with
      systemic lupus erythematosus (SLE) using a Chinese version of the Systemic Lupus
      Erythematosus-Specific Quality of Life Questionnaire (SLEQOL-C) and explore the
      factors influencing HRQOL of people with SLE. Participants were Han Chinese
      people with SLE. The SLEQOL-C and 36-item Short Form Health Survey (SF-36) were
      used to estimate the HRQOL. Disease activity was determined using the Systemic
      Lupus Erythematosus Disease Activity Index (SLEDAI) and fatigue using the
      Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Participant
      factors included age, gender, educational background, disease duration,
      erythrocyte sedimentation rate (ESR), and complement C3 and C4 levels. The
      results showed that higher SLEQQL-C scores correlated with lower SF-36 both
      measures are essential for HRQQL prediction. The SLEQOL-C scores were correlated
      with educational level,age, FACIT-F score, SLEDAI score, and ESR, which suggests
      that poor educational background, old-age, and increased fatigue, disease
      activity, and ESR might represent poor HRQOL. Although disease duration did not
      significantly correlate with the scores on the SLEQOL-C; those whose disease
      duration was 12-24 months had higher SLEQOL-C summary scores and physical
      functioning, symptoms, and treatment subscale scores than did those whose
      duration was less than 6 months. The FACIT-F score, education level, age, disease
      duration, SLEDAI score, and ESR contributed to SLEQOL-C scores. The SLEQOL-C is
      reliable for assessing HRQOL of Han Chinese people with SLE. Fatigue, educational
      level, age, disease duration, ESR, and disease activity mainly influenced HRQOL
      of SLE patients.

PMID- 29168031
TI  - Neural cells generated from human induced pluripotent stem cells as a model of
      CNS involvement in mucopolysaccharidosis type II.
AB  - Mucopolysaccharidosis type II (MPSII) is a rare X-linked lysosomal storage
      disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene (IDS, Xq28).
      MPSII is characterized by skeletal deformities, hearing loss, airway obstruction,
      hepatosplenomegaly, cardiac valvular disease, and progressive neurological
      impairment. At the cellular level, IDS deficiency leads to lysosomal storage of
      glycosaminoglycans (GAGs), dominated by accumulation of dermatan and heparan
      sulfates. Human induced pluripotent stem cells (iPSC) represent an alternative
      system that complements the available MPSII murine model. Herein we report on the
      reprogramming of peripheral white blood cells from male and female MPSII patients
      into iPSC using a non-integrating protocol based on the Sendai virus vector
      system. We differentiated the iPSC lines into IDS deficient and GAG accumulating
      beta-Tubulin III+ neurons, GFAP+ astrocytes, and CNPase+ oligodendrocytes. The
      lysosomal system in these cells displayed structural abnormalities reminiscent of
      those previously found in patient tissues and murine IDS deficient neuronal stem
      cells. Furthermore, quantitative determination of GAGs revealed a moderate
      increase in GAG levels in IDS deficient neurons and glia. We also tested the
      effects of recombinant IDS and found that the exogenous enzyme was internalized
      from the culture media and partially decreased the intracellular GAG levels in
      iPSC-derived neural cells; however, it failed to completely prevent accumulation
      of GAGs. In summary, we demonstrate that this human iPSC based model expresses
      the cellular and biochemical features of MPSII, and thus represents a useful
      experimental tool for further pathogenesis studies as well as therapy development
      and testing.

PMID- 29168032
TI  - Comparison of the MASCC and CISNE scores for identifying low-risk neutropenic
      fever patients: analysis of data from three emergency departments of cancer
      centers in three continents.
AB  - PURPOSE: Patients with febrile neutropenia are a heterogeneous group with a
      minority developing serious medical complications. Outpatient management of low
      risk febrile neutropenia has been shown to be safe and cost-effective. Scoring
      systems, such as the Multinational Association for Supportive Care in Cancer
      (MASCC) score and Clinical Index of Stable Febrile Neutropenia (CISNE), have been
      developed and validated to identify low-risk patients. We aimed to compare the
      performance of these two scores in identifying low-risk febrile neutropenic
      patients. METHODS: We performed a pooled analysis of patients presenting with
      febrile neutropenia to three tertiary cancer emergency centers in the USA, UK,
      and South Korea in 2015. The primary outcome measures were the occurrence of
      serious complications. Admission to an intensive care unit (ICU) and 30-day
      mortality were secondary outcomes. The predictive performance of each score was
      analyzed. RESULTS: Five hundred seventy-one patients presented with febrile
      neutropenia. With MASCC risk index, 508 (89.1%) were classified as low-risk
      febrile neutropenia, compared to 60 (10.5%) with CISNE classification. Overall,
      the MASCC score had a greater discriminatory power in the detection of low-risk
      patients than the CISNE score (AUC 0.772, 95% CI 0.726-0.819 vs. 0.681, 95% CI
      0.626-0.737, p = 0.0024). CONCLUSION: Both MASCC and CISNE scores have reasonable
      discriminatory value in predicting patients with low-risk febrile neutropenia.
      Risk scores should be used in conjunction with clinical judgment for the
      identification of patients suitable for outpatient management of neutropenic
      fever. Developing more accurate scores, validated in prospective settings, will
      be useful in facilitating more patients being managed in an outpatient setting.

PMID- 29168033
TI  - A prospective, multicenter pilot study to investigate the feasibility and safety
      of a 1-year controlled exercise training after adjuvant chemotherapy in
      colorectal cancer patients.
AB  - INTRODUCTION: Despite advances in adjuvant chemotherapy, 20-30% of patients in
      stages II-III colorectal cancer will eventually relapse. Observational studies
      showed a reduction in relapse rate, colon cancer-specific mortality, and overall
      mortality by physical activity. Results from prospective randomized
      interventional studies to confirm these observational data are lacking. The aims
      of this prospective single-arm multicenter pilot study are to evaluate
      feasibility and safety of exercise training after adjuvant chemotherapy in
      colorectal cancer patients. PATIENTS AND METHODS: The training was performed
      three times per week for 1 year and was increased gradually in three phases until
      reaching 18 metabolic equivalent task hours per week. RESULTS: Overall, 30
      patients were included. The planned training intensity could be achieved in all
      three phases. Patients experienced a performance increase of median 35.5 watt, a
      weight-loss of a median of 3.0 kg, and a reduction in body fat content of median
      1.0% during this exercise training. The analysis showed early study termination
      due to non-compliance in 10/30 patients (33.3%), disease progression in 4
      patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of
      patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20
      patients showed a non-significant reduction in insulin-like growth factor 1 (IGF
      1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding
      protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin
      levels, and a non-significant increase in C-peptide levels. CONCLUSION: Exercise
      training is feasible in patients with colorectal cancer after completion of
      adjuvant chemotherapy. The main problem encountered during the study was
      compliance. To improve compliance of exercise training, several measures were
      adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.

PMID- 29168034
TI  - Physical activity among cancer survivors-what is their perception and experience?
AB  - PURPOSE: Physical activity (PA) plays an important role relating to cancer. The
      aim of this study was to investigate the attitude to and experience with the
      subject of PA in cancer in a large group of tumour patients. METHODS: A
      standardised questionnaire was carried out and distributed to patients online and
      in printed form. RESULTS: Nine hundred five patients answered the questionnaire.
      Most tumour patients (60%) received information about PA after their cancer
      therapy. The Internet was often rated to be inadequate as a source of
      information. One in two tumour patients were recommended PA by a therapist.
      During the acute phase, the majority (57% of the 776) did not receive a sport
      therapeutic exercise programme. Two thirds (68%) of the 898 patients indicated
      regularly engaging in PA at least 3 or 5 days per week. In most cases (30% of the
      787), 2 to 4 h per week were dedicated to PA. In addition to a desire to increase
      well-being, enjoyment played a large role. Weakness and lack of willpower are
      among the most common barriers. Most tumour patients confirmed that PA improved
      their body awareness (58%) or gave them the feeling that they could do something
      to better cope with the disease (61%) or feel better (68%). CONCLUSION: On the
      one hand, the information requirements of tumour patients with respect to PA have
      not been adequately taken into account by practitioners. On the other hand, there
      are still subjective inhibitions on the part of the patients, which keep them
      from engaging in PA.

PMID- 29168035
TI  - Prevalence and correlates of high fear of cancer recurrence in late adolescents
      and young adults consulting a specialist adolescent and young adult (AYA) cancer
      service.
AB  - OBJECTIVE: High fear of cancer recurrence (FCR) is a frequently reported problem
      among cancer patients. Previous research has shown that younger age is associated
      with higher levels of FCR. However, little attention has been given to date about
      how FCR manifests itself among adolescent and young adult (AYA) cancer patients.
      This study explores the prevalence, correlates of high FCR, and its association
      with HRQoL in cancer patients in their late adolescence or young adulthood.
      METHODS: Seventy-three AYA cancer patients, aged 18-35 years at diagnosis,
      consulted the AYA team of the Radboud University Medical Center completed
      questionnaires including the Cancer Worry Scale (CWS), Quality of Life-Cancer
      Survivors (QOL-CS), and Hospital Anxiety and Depression Scale (HADS).
      Sociodemographic and medical data was collected by self-reported questionnaire.
      RESULTS: Forty-five participants experienced high FCR (62%), which was higher
      than the 31-52% reported in previous studies among mixed adult cancer patient
      samples. Sociodemographic and medical variables were not associated with levels
      of FCR. High FCR was significantly associated with lower levels of social and
      psychological functioning and overall HRQoL and higher levels of anxiety and
      psychological distress. CONCLUSION: Results illustrate that FCR is a significant
      problem among AYA cancer patients consulting an AYA team, with participants
      reporting higher levels of FCR than cancer patients of mixed ages. Health care
      providers should pay specific attention to this problem by screening and the
      provision of appropriate psychosocial care when needed.

PMID- 29168036
TI  - The gut microbiome, symptoms, and targeted interventions in children with cancer:
      a systematic review.
AB  - PURPOSE: The gut microbiome plays a critical role in maintaining children's
      health and in preventing and treating children's disease. Current application of
      the gut microbiome in childhood cancer is still lacking. This study aimed to
      systematically review the following: (1) alternations in the gut microbiome
      throughout cancer treatment trajectories in children, (2) the associations
      between the gut microbiome and gastrointestinal (GI) symptoms and
      psychoneurological symptoms (PNS), and (3) the efficacy of therapeutic
      interventions in the gut microbiome in children with cancer. METHODS: PubMed,
      EMBASE, the Cochrane Library, and the American Society of Clinical Oncology
      abstract were searched. Eligible studies included all study types in which the
      gut microbiome was primarily reported in children with cancer. The Mixed Methods
      Assessment Tool was used to evaluate the methodology quality of included studies.
      Seven studies met our eligibility criteria, including two cohort studies, two
      case-control studies, and three randomized controlled trails. RESULTS: The
      findings showed that the diversity estimates of the gut microbiome in children
      with cancer were lower than those of healthy controls both pre- and post
      treatment. Children with cancer showed a significantly lower relative abundance
      of healthy gut microbiome (e.g., Clostridium XIVa and Bifidobacterium) during and
      after cancer treatment. No adequate literature was identified to support the
      associations between dysbiosis of the gut microbiome and GI symptoms/PNS. The use
      of prebiotics (fructooligosaccharides) and probiotics (Bifidobacterium or
      Lactobacilli) appears to improve the microenvironment of the gut around 1 month
      (4-5 weeks) during chemotherapy rather than at the beginning of treatment. Data
      also suggest that both prebiotic and probiotic interventions decrease clinical
      side effects (e.g., infection and morbidity risk) in children with cancer.
      CONCLUSIONS: This study adds to the evidence that dysbiosis of the gut microbiome
      can be improved using prebiotic and probiotic supplementations in children with
      cancer. More well-designed experimental studies are needed to confirm this
      conclusion. Further studies are needed to examine the associations between the
      gut microbiome and GI symptoms/PNS in childhood cancer.

PMID- 29168037
TI  - Efficacy and safety of reinfusion of concentrated ascitic fluid for malignant
      ascites: a concept-proof study.
AB  - PURPOSE: Malignant ascites is one of the symptoms causing discomfort in advanced
      cancer patients. Cell-free and concentrated ascites reinfusion therapy (CART) is
      one treatment modality, but controlled trials are limited. The primary aim of
      this study was to explore the efficacy and safety of CART, as well as their
      predictors, to obtain data for planning a further controlled trial. METHODS: This
      was a single center retrospective cohort study in patients with refractory
      malignant ascites. Consecutive adult patients who underwent CART were enrolled.
      The primary endpoints were the time to next paracentesis and seven patient
      reported symptoms (e.g., abdominal pain and distension). The secondary endpoints
      were adverse events, laboratory findings, and physical findings. RESULTS: A total
      of 104 CART procedures for 51 patients were analyzed. The median time to next
      paracentesis was 27 days (95% CI, 21-35). Intensities of all seven symptoms were
      significantly improved after CART (p < 0.0001 for all symptoms). Grade 3
      hypotension occurred during one procedure, and mild fever occurred in 5%. Total
      protein, albumin, and estimated glomerular filtration rate were significantly
      increased. Hemorrhagic ascites, ascites white blood cell count, serum total
      protein, and lymphocyte percentages were the independent predictors of the time
      to next paracentesis. CONCLUSION: The effects of reinfusion of concentrated
      ascitic fluid may be maintained for 1 month, being potentially longer than that
      of total paracentesis alone. This study had no comparison groups and examined the
      short-term effect. A randomized controlled study to compare the long-term effects
      of total paracentesis alone vs. CART is necessary.

PMID- 29168038
TI  - Ovarian serous carcinomas acquire cisplatin resistance and increased invasion
      through downregulation of the high-temperature-required protein A2 (HtrA2),
      following repeated treatment with cisplatin.
AB  - High-temperature-required protein A2 (HtrA2) is one of the serine proteases
      related to apoptosis. HtrA2 protein expression has been associated with cisplatin
      resistance and poor prognosis in ovarian serous adenocarcinoma (SAC). The aim of
      this study was to understand the influence of HtrA2 on repeated treatment with
      cisplatin. The change in HtrA2 expression in 31 ovarian cancers was investigated
      by immunohistochemical analysis, before and after cisplatin-based chemotherapy,
      and the association between HtrA2 expression after chemotherapy and prognosis was
      analyzed. The association between the change in HtrA2 and proteins associated
      with LATS1 in ovarian serous cancer cell lines after repeated treatment with
      cisplatin was evaluated in vitro. In immunohistochemical analysis, repeated
      cisplatin treatment induced downregulation of HtrA2 protein expression, before
      and after cisplatin-based chemotherapy in SAC. Progression-free survival and
      overall survival of SAC with low expression of HtrA2 were worse than those with
      high expression. In vitro analysis using cisplatin-sensitive ovarian cancer cell
      lines, KF28, and cisplatin-resistant cancer cell lines, KFr13, obtained from KF28
      by repeated cisplatin treatment, showed that HtrA2 protein expression was lower
      in KFr13 than in KF28. Furthermore, KFr13 had a higher invasive capacity than
      KF28. Next, downregulation of HtrA2 transfected with an HtrA2-specific siRNA in
      KF28 had not only cisplatin resistance, but also more invasive capacity than
      those with non-specific siRNA. Repeated treatment with cisplatin downregulated
      the HtrA2 protein, which led to cisplatin resistance and increased invasive
      capacity. Thus, HtrA2 might be a biomarker of response to cisplatin treatment and
      prognosis, after cisplatin-based chemotherapy.

PMID- 29168039
TI  - Sequential Detection of Compromised Items Using Response Times in Computerized
      Adaptive Testing.
AB  - Item compromise persists in undermining the integrity of testing, even secure
      administrations of computerized adaptive testing (CAT) with sophisticated item
      exposure controls. In ongoing efforts to tackle this perennial security issue in
      CAT, a couple of recent studies investigated sequential procedures for detecting
      compromised items, in which a significant increase in the proportion of correct
      responses for each item in the pool is monitored in real time using moving
      averages. In addition to actual responses, response times are valuable
      information with tremendous potential to reveal items that may have been leaked.
      Specifically, examinees that have preknowledge of an item would likely respond
      more quickly to it than those who do not. Therefore, the current study proposes
      several augmented methods for the detection of compromised items, all involving
      simultaneous monitoring of changes in both the proportion correct and average
      response time for every item using various moving average strategies. Simulation
      results with an operational item pool indicate that, compared to the analysis of
      responses alone, utilizing response times can afford marked improvements in
      detection power with fewer false positives.

PMID- 29168040
TI  - The utility of home sleep apnea tests in patients with low versus high pre-test
      probability for moderate to severe OSA.
AB  - PURPOSE: Home sleep apnea tests (HSATs) are an alternative to attended
      polysomnograms (PSGs) when the pre-test probability for moderate to severe OSA is
      high. However, insurers often mandate use anytime OSA is suspected regardless of
      the pre-test probability. Our objective was to determine the ability of HSATs to
      rule in OSA when the pre-test probability of an apnea hypopnea index (AHI) in the
      moderate to severe range is low. METHODS: Patients who underwent HSATs were
      characterized as low or high pre-test probability based on the presence of two
      symptoms of the STOP instrument plus either BMI > 35 or male gender. The odds of
      HSAT diagnostic for OSA dependent on pre-test probability was calculated.
      Stepwise selection determined predictors of non-diagnostic HSAT. As PSG is
      performed after HSATs that do not confirm OSA, false negative results were
      assessed. RESULTS: Among 196 individuals, pre-test probability was low in 74
      (38%) and high in 122 (62%). A lower percentage of individuals with a low versus
      high pre-test probability for moderate to severe OSA had HSAT results that
      confirmed OSA (61 versus 84%, p = 0.0002) resulting in an odds ratio (OR) of 0.29
      for confirmatory HSAT in the low pre-test probability group (95% CI [0.146,
      0.563]). Multivariate logistic regression demonstrated that age <= 50 (OR 3.10
      [1.24-7.73]), female gender (OR 3.58[1.50-8.66]), non-enlarged neck circumference
      (OR 11.50 [2.50-52.93]), and the absence of loud snoring (OR 3.47 [1.30-9.25])
      best predicted non-diagnostic HSAT. OSA was diagnosed by PSG in 54% of
      individuals with negative HSAT which was similar in both pre-test probability
      groups. CONCLUSION: HSATs should be reserved for individuals with high pre-test
      probability for moderate to severe disease as opposed to any individual with
      suspected OSA.

PMID- 29168041
TI  - Making Sense of SNPs: Women's Understanding and Experiences of Receiving a
      Personalized Profile of Their Breast Cancer Risks.
AB  - Genome wide association studies have identified a number of common genetic
      variants - single nucleotide polymorphisms (SNPs) - that combine to increase
      breast cancer risk. SNP profiling may enhance the accuracy of risk assessment and
      provides a personalized risk estimate. SNP testing for breast cancer risks may
      supplement other genetic tests in the future, however, before it can be
      implemented in the clinic we need to know how it will be perceived and received.
      Semi-structured qualitative interviews were conducted with 39 women who had
      previously had a breast cancer diagnosis and undergone BRCA1/2 testing,
      participated in the Variants in Practice (ViP) study and received personalized
      risk (SNP) profiles. Interviews explored their understanding and experiences of
      receiving this SNP information. Women reported feeling positive about receiving
      their personalized risk profile, because it: provided an explanation for their
      previous diagnosis of cancer, vindicated previous risk management decisions and
      clarified their own and other family members' risks. A small group was initially
      shocked to learn of the increased risk of a second primary breast cancer. This
      study suggests that the provision of personalized risk information about breast
      cancer generated by SNP profiling is understood and well received. However, a
      model of genetic counseling that incorporates monogenic and polygenic genetic
      information will need to be developed prior to clinical implementation.

PMID- 29168042
TI  - Impact of Receiving Secondary Results from Genomic Research: A 12-Month
      Longitudinal Study.
AB  - The impact of returning secondary results from exome sequencing (ES) on
      patients/participants is important to understand as ES is increasingly utilized
      in clinical care and research. Participants were recruited from studies using ES
      and were separated into two arms: 107 who had ES and were offered the choice to
      learn secondary results (ES group) and 85 who had not yet had ES (No ES group).
      Questionnaires were administered at baseline and 1 and 12 months, following
      results disclosure (ES group) or enrollment (No ES group). While the majority
      (65%) elected to learn all results following pre-test counseling, it was reduced
      from the 76% who indicated a desire for all results at baseline. Thirty-seven
      percent received results associated with an increased personal disease risk.
      There were no differences in changes in any of the psychological and social
      measures from baseline to post-results disclosure between the ES and No ES
      groups. Receiving a wide range of secondary findings appeared to have little
      measurable impact on most participants. The experience of learning secondary
      results may be related to participants' previous experiences with genetics, as
      well as the genetic counseling provided. Future research with a more diverse,
      genetically naive group, as well as scalable methods of delivery, is needed.

PMID- 29168043
TI  - Role of CYP1B1, p.E229K and p.R368H mutations among 120 families with sporadic
      juvenile onset open-angle glaucoma.
AB  - BACKGROUND: To determine the frequency of CYP1B1 p.E229K and p.R368H, gene
      mutations in a cohort of sporadic juvenile onset open-angle glaucoma (JOAG)
      patients and to evaluate their genotype/phenotype correlation. METHODS: Unrelated
      JOAG patients whose first-degree relatives had been examined and found to be
      unaffected were included in the study. The patients and their parents were
      screened for p.E229K and p.R368H mutations. The phenotypic characteristics were
      compared between probands carrying the mutations and those who did not carry
      these mutations. RESULTS: Out of 120 JOAG patients included in the study, the
      p.E229K mutation was seen in 9 probands (7.5%) and p.R368H in 7 (5.8%). The
      average age of onset of the disease (p = 0.3) and the highest untreated IOP (p =
      0.4) among those carrying mutations was not significantly different from those
      who did not have these mutations. The proportion of probands with angle
      dysgenesis among those with p.E229K and p.R368H mutations was 70% (11 out of 16)
      in comparison to 65% (67 out of 104) of those who did not harbour these mutations
      (p = 0.56). Similarly, the probands with moderate to high myopia among those with
      p.E229K and p.R368H mutations was 20% (3 out of 16) in comparison to 18% (18 out
      of 104) of those who did not harbour these mutations (p = 0.59). CONCLUSION: The
      frequency of p.E229K and p.R368H mutations of the CYP1B1 gene is low even among
      sporadic JOAG patients. Moreover, there is no clinical correlation between the
      presence of these mutations and disease severity.

PMID- 29168044
TI  - Potential selection bias in candidates for stereotactic radiotherapy for
      neovascular AMD.
AB  - PURPOSE: Stereotactic radiotherapy (SRT, IRay) was able to reduce the need for
      intravitreal injections of anti-VEGF (IVI) in patients with neovascular AMD
      (nAMD) in a phase II randomized clinical trial. Certain morphologic
      characteristics, such as lesion size < 4 mm2 or lack of fibrosis, were associated
      with a better response. The purpose of this cross-sectional study was to
      investigate eligibility for SRT in a clinical routine setting and to compare
      clinical features of eligible and non-eligible patients. METHODS: Cross-sectional
      study of 468 patients treated for nAMD in one study center within a period of 4
      months. Clinical features, such as visual acuity or number of IVI since diagnosis
      and within 6/12 months, as well as the presence for exclusion criteria for SRT
      were analyzed. Exclusion criteria were sub-divided into lesion-associated
      (relevant fibrosis, lesion size > 4 mm2, PE tear), ocular comorbidity (e.g.,
      macular comorbidity, vascular disease) and systemic comorbidity (e.g., dementia
      or tremor). RESULTS: Exclusion criteria were met by 255 patients (54.5%).
      Exclusion was most dominantly associated with lesion-associated criteria (80.0%)
      and less often with ocular (20.8%) or systemic (9.4%) comorbidity. A total of 213
      patients (45.5%) fulfilled eligibility criteria. Eligible patients had a better
      VA at time of analysis (0.36 vs. 0.56 logMAR, p < 0.0001) and at baseline (0.38
      vs. 0.56 logMAR, p < 0.0001) compared to non-eligible patients. The numbers of
      previous intravitreal injections since diagnosis in strictly PRN-treated patients
      served as a surrogate marker for lesion activity and was comparable within the
      last 6/12 months. Non-eligible patients had a higher number of different anti
      VEGF drugs (1.8 vs. 1.6, p = 0.038). CONCLUSIONS: SRT in addition to anti-VEGF
      can be an option in every second patient with nAMD. Due to morphological
      exclusion criteria, patients eligible for SRT had a better VA and a better
      clinical response compared to non-eligible patients.

PMID- 29168045
TI  - Biocompatibility of intravitreal injection of human mesenchymal stem cells in
      immunocompetent rabbits.
AB  - PURPOSE: To evaluate the feasibility, safety, and biocompatibility of
      intravitreal injection of human mesenchymal stem cells (MSCs) in immunocompetent
      pigmented rabbits. MATERIALS AND METHODS: Thirty-two pigmented rabbits (24
      females, 8 males; Chinchilla-New Zealand White) were divided into 8 groups of 4
      animals. Commercially prepared human MSCs were injected (0.05 ml) into the post
      lens vitreous of the right eyes. Groups 1 and 4 received isotonic medium (Ringer
      lactate-based), groups 2, 5, 7, and 8 received a low dose of 15 * 106 cells/ml.
      Groups 3 and 6 received a high dose of 30 * 106 cells/ml. Clinical signs were
      evaluated and scored before MSCs injection and weekly for 2 or 6 weeks. Animals
      were sacrificed at 2 or 6 weeks after injection. Eyes, liver, spleen, and gonads
      were assessed by histology and by fluorescent in situ hybridization to evaluate
      survival and extraocular migration of MSCs. RESULTS: There were no relevant
      clinical findings between control and MSC-injected rabbit eyes at any time point.
      There were also no relevant histological findings between control and MSC
      injected rabbits related to ocular, liver, spleen, or gonad tissues
      modifications. MSCs survived intravitreally for at least 2 weeks after injection.
      Extraocular migration of MSCs was not detected. CONCLUSIONS: MSCs are safe and
      well-tolerated when administered intravitreally at a dose of 15 * 106 cells/ml in
      pigmented rabbits. These findings enable future research to explore the
      intravitreal use of commercially prepared allogenic human MSCs in clinical trials
      of retinal diseases.

PMID- 29168046
TI  - Procalcitonin-guided antibiotic therapy in intensive care unit patients: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Serum procalcitonin (PCT) concentration is used to guide antibiotic
      decisions in choice, timing, and duration of anti-infection therapy to avoid
      antibiotic overuse. Thus, we performed a systematic review and meta-analysis to
      seek evidence of different PCT-guided antimicrobial strategies for critically ill
      patients in terms of predefined clinical outcomes. METHODS: We searched for
      relevant studies in PubMed, Embase, Web of Knowledge, and the Cochrane Library up
      to 25 February 2017. Randomized controlled trials (RCTs) were included if they
      reported data on any of the predefined outcomes in adult ICU patients managed
      with a PCT-guided algorithm or according to standard care. Results were expressed
      as risk ratio (RR) or mean difference (MD) with accompanying 95% confidence
      interval (CI). DATA SYNTHESIS: We included 13 trials enrolling 5136 patients.
      These studies used PCT in three clinical strategies: initiation, discontinuation,
      or combination of antibiotic initiation and discontinuation strategies. Pooled
      analysis showed a PCT-guided antibiotic discontinuation strategy had fewer total
      days with antibiotics (MD - 1.66 days; 95% CI - 2.36 to - 0.96 days), longer
      antibiotic-free days (MD 2.26 days; 95% CI 1.40-3.12 days), and lower short-term
      mortality (RR 0.87; 95% CI 0.76-0.98), without adversely affecting other
      outcomes. Only few studies reported data on other PCT-guided strategies for
      antibiotic therapies, and the pooled results showed no benefit in the predefined
      outcomes. CONCLUSIONS: Our meta-analysis produced evidence that among all the PCT
      based strategies, only using PCT for antibiotic discontinuation can reduce both
      antibiotic exposure and short-term mortality in a critical care setting.

PMID- 29168047
TI  - Are Eating Disorders Risk Factors for Type 2 Diabetes? A Systematic Review and
      Meta-analysis.
AB  - RECENT FINDINGS: Eating disorders (ED) affect energy intake modifying body fat
      depots. Prior evidence suggests that binge eating disorder (BED) and bulimia
      nervosa (BN) could increase the risk for type 2 diabetes (T2D), while anorexia
      nervosa (AN) could reduce it. PURPOSE OF REVIEW: A systematic review and meta
      analysis were conducted to evaluate if ED are risk factors for T2D. Ten studies
      were selected out of 1057 screened. Meta-analysis of six studies with T2D as
      outcome is reported. Among cross-sectional studies, both BED (OR 3.69, 95% CI
      [1.12-12.12]) and BN (OR 3.45 [1.92-6.1]) increased the risk of T2D, while AN was
      not associated with lower risk (OR 0.87 [0.40-1.88]). Cohort studies showed
      increased risk of T2D with BN (RR 1.7 [1.2-2.5]), and decreased risk with AN (RR
      0.71 [0.52-0.98]), but for BED the association was less clear (OR 3.34 [0.85
      13.12]). Limitations of studies and recommendations for future research are
      presented.

PMID- 29168048
TI  - Homozygous Expression of Mutant ELOVL4 Leads to Seizures and Death in a Novel
      Animal Model of Very Long-Chain Fatty Acid Deficiency.
AB  - Lipids are essential components of the nervous system. However, the functions of
      very long-chain fatty acids (VLC-FA; >= 28 carbons) in the brain are unknown. The
      enzyme ELOngation of Very Long-chain fatty acids-4 (ELOVL4) catalyzes the rate
      limiting step in the biosynthesis of VLC-FA (Agbaga et al., Proc Natl Acad Sci
      USA 105(35): 12843-12848, 2008; Logan et al., J Lipid Res 55(4): 698-708, 2014),
      which we identified in the brain as saturated fatty acids (VLC-SFA). Homozygous
      mutations in ELOVL4 cause severe neuropathology in humans (Ozaki et al., JAMA
      Neurol 72(7): 797-805, 2015; Mir et al., BMC Med Genet 15: 25, 2014; Cadieux-Dion
      et al., JAMA Neurol 71(4): 470-475, 2014; Bourassa et al., JAMA Neurol 72(8): 942
      943, 2015; Aldahmesh et al., Am J Hum Genet 89(6): 745-750, 2011) and are post
      natal lethal in mice (Cameron et al., Int J Biol Sci 3(2): 111-119, 2007; Li et
      al., Int J Biol Sci 3(2): 120-128, 2007; McMahon et al., Molecular Vision 13: 258
      272, 2007; Vasireddy et al., Hum Mol Genet 16(5): 471-482, 2007) from dehydration
      due to loss of VLC-SFA that comprise the skin permeability barrier. Double
      transgenic mice with homozygous knock-in of the Stargardt-like macular dystrophy
      (STDG3; 797-801_AACTT) mutation of Elovl4 with skin-specific rescue of wild-type
      Elovl4 expression (S + Elovl4 mut/mut mice) develop seizures by P19 and die by
      P21. Electrophysiological analyses of hippocampal slices showed aberrant
      epileptogenic activity in S + Elovl4 mut/mut mice. FM1-43 dye release studies
      showed that synapses made by cultured hippocampal neurons from S + Elovl4 mut/mut
      mice exhibited accelerated synaptic release kinetics. Supplementation of VLC-SFA
      to cultured hippocampal neurons from mutant mice rescued defective synaptic
      release to wild-type rates. Together, these studies establish a critical, novel
      role for ELOVL4 and its VLC-SFA products in regulating synaptic release kinetics
      and epileptogenesis. Future studies aimed at understanding the molecular
      mechanisms by which VLC-SFA regulate synaptic function may provide new targets
      for improved seizure therapies.

PMID- 29168050
TI  - Using Gene Transcription to Assess Ecological and Anthropological Stressors in
      Brown Bears.
AB  - Increasingly, population- and ecosystem-level health assessments are performed
      using sophisticated molecular tools. Advances in molecular technology enable the
      identification of synergistic effects of multiple stressors on the individual
      physiology of different species. Brown bears (Ursus arctos) are an apex predator;
      thus, they are ideal candidates for detecting potentially ecosystem-level
      systemic perturbations using molecular-based tools. We used gene transcription to
      analyze 130 brown bear samples from three National Parks and Preserves in Alaska.
      Although the populations we studied are apparently stable in abundance and exist
      within protected and intact environments, differences in transcript profiles were
      noted. The most prevalent differences were among locations. The transcript
      patterns among groups reflect the influence of environmental factors, such as
      nutritional status, disease, and xenobiotic exposure. However, these profiles
      also likely represent baselines for each unique environment by which future
      measures can be made to identify early indication of population-level changes due
      to, for example, increasing Arctic temperatures. Some of those environmental
      changes are predicted to be potentially positive for brown bears, but other
      effects such as the manifestation of disease or indirect effects of oceanic
      acidification may produce negative impacts.

PMID- 29168051
TI  - Efficient conformational ensemble generation of protein-bound peptides.
AB  - Conformation generation of protein-bound peptides is critical for the
      determination of protein-peptide complex structures. Despite significant progress
      in conformer generation of small molecules, few methods have been developed for
      modeling protein-bound peptide conformations. Here, we have developed a fast de
      novo peptide modeling algorithm, referred to as MODPEP, for conformational
      sampling of protein-bound peptides. Given a sequence, MODPEP builds the peptide
      3D structure from scratch by assembling amino acids or helix fragments based on
      constructed rotamer and helix libraries. The MODPEP algorithm was tested on a
      diverse set of 910 experimentally determined protein-bound peptides with 3-30
      amino acids from the PDB and obtained an average accuracy of 1.90 A when 200
      conformations were sampled for each peptide. On average, MODPEP obtained a
      success rate of 74.3% for all the 910 peptides and >= 90% for short peptides with
      3-10 amino acids in reproducing experimental protein-bound structures.
      Comparative evaluations of MODPEP with three other conformer generation methods,
      PEP-FOLD3, RDKit, and Balloon, have also been performed in both accuracy and
      success rate. MODPEP is fast and can generate 100 conformations for less than one
      second. The fast MODPEP will be beneficial for large-scale de novo modeling and
      docking of peptides. The MODPEP program and libraries are available for download
      at http://huanglab.phys.hust.edu.cn/ .

PMID- 29168053
TI  - The sociobiology of genes: the gene's eye view as a unifying behavioural
      ecological framework for biological evolution.
AB  - Although classical evolutionary theory, i.e., population genetics and the Modern
      Synthesis, was already implicitly 'gene-centred', the organism was, in practice,
      still generally regarded as the individual unit of which a population is
      composed. The gene-centred approach to evolution only reached a logical
      conclusion with the advent of the gene-selectionist or gene's eye view in the
      1960s and 1970s. Whereas classical evolutionary theory can only work with
      (genotypically represented) fitness differences between individual organisms,
      gene-selectionism is capable of working with fitness differences among genes
      within the same organism and genome. Here, we explore the explanatory potential
      of 'intra-organismic' and 'intra-genomic' gene-selectionism, i.e., of a
      behavioural-ecological 'gene's eye view' on genetic, genomic and organismal
      evolution. First, we give a general outline of the framework and how it
      complements the-to some extent-still 'organism-centred' approach of classical
      evolutionary theory. Secondly, we give a more in-depth assessment of its
      explanatory potential for biological evolution, i.e., for Darwin's 'common
      descent with modification' or, more specifically, for 'historical continuity or
      homology with modular evolutionary change' as it has been studied by evolutionary
      developmental biology (evo-devo) during the last few decades. In contrast with
      classical evolutionary theory, evo-devo focuses on 'within-organism'
      developmental processes. Given the capacity of gene-selectionism to adopt an
      intra-organismal gene's eye view, we outline the relevance of the latter model
      for evo-devo. Overall, we aim for the conceptual integration between the gene's
      eye view on the one hand, and more organism-centred evolutionary models (both
      classical evolutionary theory and evo-devo) on the other.

PMID- 29168052
TI  - Change in health-related quality of life and social cognitive outcomes in obese,
      older adults in a randomized controlled weight loss trial: Does physical activity
      behavior matter?
AB  - This article compared the effect of dietary weight loss administered alone (WL)
      or in combination with aerobic training (WL + AT) or resistance training (WL +
      RT) on health related quality of life, walking self-efficacy, stair climb self
      efficacy, and satisfaction with physical function in older adults with
      cardiovascular disease or the metabolic syndrome. Participants (N = 249; M age =
      66.9) engaged in baseline assessments and were randomly assigned to one of three
      interventions, each including a 6-month intensive phase and a 12-month follow-up.
      Those in WL + AT and WL + RT engaged in 4 days of exercise training weekly. All
      participants engaged in weekly group behavioral weight loss sessions with a goal
      of 7-10% reduction in body weight. Participants in WL + AT and WL + RT reported
      better quality of life and satisfaction with physical function at 6- and 18
      months relative to WL. At month 6, WL + AT reported greater walking self-efficacy
      relative to WL + RT and WL, and maintained higher scores compared to WL at month
      18. WL + AT and WL + RT reported greater stair climbing efficacy at month 6, and
      WL + RT remained significantly greater than WL at month 18. The addition of
      either AT or RT to WL differentially improved HRQOL and key psychosocial outcomes
      associated with maintenance of physical activity and weight loss. This
      underscores the important role of exercise in WL for older adults, and suggests
      health care providers should give careful consideration to exercise mode when
      designing interventions.

PMID- 29168054
TI  - Cardiac function in patients with polymyositis or dermatomyositis: a three
      dimensional speckle-tracking echocardiography study.
AB  - Cardiac event is a major cause of death in patients with idiopathic inflammatory
      myopathies (IIM). The most frequent IIMs are polymyositis (PM) and
      dermatomyositis (DM). The purpose of this study was to analyze cardiac
      involvement by three-dimensional speckle-tracking echocardiography (3D STE) in
      patients with PM or DM, and to identify the relationship of cardiac injury with
      clinical characteristics and disease-specific parameters. 60 PM/DM patients with
      preserved left ventricular ejection fraction and 30 matched healthy controls were
      assessed by conventional echocardiography, 3D STE with biventricular strain
      analysis and electrocardiogram. Compared to controls, patients with PM/DM had
      significantly diminished left ventricular global longitudinal systolic strain and
      right ventricular longitudinal systolic strain (LVGLS, - 20.3 +/- 2.5 vs. - 23.4
      +/- 1.7%; RVLS, - 19.4 +/- 4.2 vs - 24.8 +/- 2.0%; both P < 0.001), and longer
      QTc intervals(421.0 +/- 38.4 vs 400.6 +/- 14.5 ms, P = 0.001). Multiple
      regression analysis showed that Myositis Damage Index (MDI) was independently
      associated with LVGLS (R2 = 0.44, P = 0.002) and RVLS (R2 = 0.56, P < 0.001) in
      PM/DM patients with established disease course more than 1 year. In multivariate
      analysis of pooled data for all the PM/DM patients, when MDI was excluded due to
      missing observations, disease duration correlated with worse LVGLS (R2 = 0.24, P
      = 0.002), while concomitant interstitial lung disease correlated with worse RVLS
      (R2 = 0.30, P < 0.001). Disease activity scores (Myositis Intention to Treat
      Activities Index) had a weak positive correlation with QTc intervals (rsp = 0.31,
      P = 0.02). Our results suggest that cardiac injury in PM/DM is a long-term
      process and its severity depends on patients' heterogeneous clinical features and
      systemic disease burden.

PMID- 29168055
TI  - Reproducibility of peak filling and peak emptying rate determined by
      cardiovascular magnetic resonance imaging for assessment of biventricular
      systolic and diastolic dysfunction in patients with pulmonary arterial
      hypertension.
AB  - Right ventricular (RV) and left ventricular (LV) diastolic stiffness may be
      independent contributors to disease progression in pulmonary arterial
      hypertension (PAH). The aims of this study are to assess reproducibility of peak
      emptying rate (PER) and early diastolic peak filling rate (PFR) for both the RV
      and the LV in PAH and study their relationship to stroke volume (SV). Triple
      weekly repetition of 20 (totalling 60) cardiovascular magnetic resonance (CMR)
      scans, were done on 10 patients with PAH and 10 healthy controls. RV and LV
      volumes were measured over the full cardiac cycle. PER and PFR were calculated as
      the first derivative of the time-volume relationship in both the RV and the LV
      and indexed to body surface area. Reproducibility and the relation to SV were
      studied in a mixed model. PFR was lower in PAH in both the RV (PAH = 170 mL/m2/s,
      controls = 236 mL/m2/s [p < 0.01]) and in the LV (PAH = 209 mL/m2/s, controls =
      311 mL/m2/s [p < 0.01]). PERs were not significantly different between patients
      and controls. Reproducibility of PER and PFR was high. A trial targeting
      normalization of PFR requires a total sample size of < 20. PER and PFR in both
      ventricles were strongly associated with stroke volume (all four: p < 0.01).
      Biventricular diastolic dysfunctions are strongly associated with stroke volume,
      and CMR can quantify them with high reproducibility, enabling small sample sizes
      for trials of therapies targeting diastolic dysfunction to increase survival.

PMID- 29168056
TI  - In vivo therapeutic potential of Inula racemosa in hepatic ischemia-reperfusion
      injury following orthotopic liver transplantation in male albino rats.
AB  - Hepatic ischemia-reperfusion (I/R) injury mainly occurs following hepatic
      resection and liver transplantation and cause severe liver damage, organ
      injuries, and dysfunction. Pro-inflammatory cytokines that promote injury are
      released when kupffer cell activates after getting induced by I/R. Repercussions
      of oxidative stress and cardiac function against isoproterenol based myocardial
      infarction are caused by flavonol glycosides which are found in high
      concentrations in Inula racemosa (Ir).The root was deemed to have analgesic and
      anti-inflammatory effects, and no report has been published about the liver
      protective activity against hepatic I/R. Therefore, the present study was aimed
      to understand the therapeutic impact of Ir in hepatic I/R injury. Male albino,
      Wistar strain rats were used and were grouped into four total phenolic content,
      free radical scavenging activity and serum enzymes were determined.
      Histopathological and immunohistochemical analysis were also carried out.
      Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and
      interleukin (IL-6) and protein expression of p53, bax, and bcl-2 were determined.
      The administration of extracts of Ir significantly increased total phenolic and
      free radical scavenging activity. Altered cellular morphology, cytokines and
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline
      phosphatase (ALP), and lactate dehydrogenase (LDH) were returned to near normal
      level. IL-6 and TNF-alpha levels were reduced more than 25% following treatment.
      Also, the protein expression of p53, bax, and bcl-2 were also returned to near
      normal level. Taking all these data together, it is suggested that the extracts
      of Ir may be a potential therapeutic agent for providing several beneficial
      effects in hepatic I/R injury.

PMID- 29168057
TI  - 1H, 15N and 13C backbone resonance assignments of pentaerythritol tetranitrate
      reductase from Enterobacter cloacae PB2.
AB  - Pentaerythritol tetranitrate reductase (PETNR) is a flavoenzyme possessing a
      broad substrate specificity and is a member of the Old Yellow Enzyme family of
      oxidoreductases. As well as having high potential as an industrial biocatalyst,
      PETNR is an excellent model system for studying hydrogen transfer reactions.
      Mechanistic studies performed with PETNR using stopped-flow methods have shown
      that tunneling contributes towards hydride transfer from the NAD(P)H coenzyme to
      the flavin mononucleotide (FMN) cofactor and fast protein dynamics have been
      inferred to facilitate this catalytic step. Herein, we report the near-complete
      1H, 15N and 13C backbone resonance assignments of PETNR in a stoichiometric
      complex with the FMN cofactor in its native oxidized form, which were obtained
      using heteronuclear multidimensional NMR spectroscopy. A total of 97% of all
      backbone resonances were assigned, with 333 out of a possible 344 residues
      assigned in the 1H-15N TROSY spectrum. This is the first report of an NMR
      structural study of a flavoenzyme from the Old Yellow Enzyme family and it lays
      the foundation for future investigations of functional dynamics in hydride
      transfer catalytic mechanism.

PMID- 29168058
TI  - Analysis of Siamese Crocodile (Crocodylus siamensis) Eggshell Proteome.
AB  - The proteins and pigment of the eggshell of the Siamese crocodile (Crocodylus
      siamensis) were analysed. For proteomic analysis, various decalcification methods
      were used when the two main surface layers were analyzed. These layers are
      important for antimicrobial defense of egg (particularly the cuticle). We found
      58 proteins in both layers, of which 4 were specific for the cuticle and 26 for
      the palisade (honeycomb) layer. Substantial differences between proteins in the
      eggshell of crocodile and previously described birds' eggshells exist (both in
      terms of quality and quantity), however, the entire proteome of Crocodilians has
      not been described yet. The most abundant protein was thyroglobulin. The role of
      determined proteins in the eggshell of the Siamese crocodile is discussed. For
      the first time, the presence of porphyrin pigment is reported in a crocodilian
      eggshell, albeit in a small amount (about 2 to 3 orders of magnitude lower than
      white avian eggs).

PMID- 29168059
TI  - Sec61beta facilitates the maintenance of endoplasmic reticulum homeostasis by
      associating microtubules.
AB  - Sec61beta, a subunit of the Sec61 translocon complex, is not essential in yeast
      and commonly used as a marker of endoplasmic reticulum (ER). In higher
      eukaryotes, such as Drosophila, deletion of Sec61beta causes lethality, but its
      physiological role is unclear. Here, we show that Sec61beta interacts directly
      with microtubules. Overexpression of Sec61beta containing small epitope tags, but
      not a RFP tag, induces dramatic bundling of the ER and microtubule. A basic
      region in the cytosolic domain of Sec61beta is critical for microtubule
      association. Depletion of Sec61beta induces ER stress in both mammalian cells and
      Caenorhabditis elegans, and subsequent restoration of ER homeostasis correlates
      with the microtubule binding ability of Sec61beta. Loss of Sec61beta causes
      increased mobility of translocon complexes and reduced level of membrane-bound
      ribosomes. These results suggest that Sec61beta may stabilize protein
      translocation by linking translocon complex to microtubule and provide insight
      into the physiological function of ER-microtubule interaction.

PMID- 29168061
TI  - Abstracts - Indian Society of Gastroenterology.

PMID- 29168060
TI  - The Role of Physician Recommendation in Colorectal Cancer Screening Receipt Among
      Immigrant Chinese Americans.
AB  - Chinese Americans have low colorectal cancer (CRC) screening rates. It is unclear
      whether physicians should offer all CRC screening modalities (fecal occult blood
      test [FOBT], sigmoidoscopy, colonoscopy) to Chinese Americans to increase
      screening. Seven hundred and twenty-five Chinese Americans were asked in a survey
      if their physician had ever recommended CRC screening and to self-report receipt
      and type of CRC screening. Participants whose physician had recommended all CRC
      screening modalities were significantly more likely to report ever having
      screening (adjusted odds ratio 4.29, 95% CI 1.26-14.68) and being up-to-date
      (4.06, 95% CI 2.13-7.74) than those who reported that their physician only
      recommended FOBT. Participants who received a recommendation of only one type of
      screening did not report a significant difference in ever having or being up-to
      date for screening. A potential strategy to increase CRC screening among Chinese
      Americans is for clinicians to recommend all available CRC screening modalities
      to each patient.

PMID- 29168062
TI  - Tree nut, peanut, and peanut butter intake and risk of postmenopausal breast
      cancer: The Netherlands Cohort Study.
AB  - PURPOSE: Nut intake has been associated with reduced mortality and risk of
      cardiovascular diseases, but there is only limited evidence on cancer. We
      investigated the relationship between nut intake and risk of postmenopausal
      breast cancer, and estrogen/progesterone receptor (ER/PR) subtypes. METHODS: In
      The Netherlands Cohort Study, 62,573 women aged 55-69 years provided information
      on dietary and lifestyle habits in 1986. After 20.3 years of follow-up, 2,321
      incident breast cancer cases and 1,665 subcohort members were eligible for
      multivariate case-cohort analyses. RESULTS: Total nut intake was significantly
      inversely related to ER negative (ER -) breast cancer risk, with HR 0.55 (95% CI
      0.33-0.93) for those consuming at least 10 g nuts/day versus non-consumers (p
      trend = 0.025). There were no significant inverse associations with ER + or total
      breast cancer. While there was no variation between PR subtypes, the ER-PR-
      subtype was also significantly inversely associated with nut intake, with HR 0.53
      (95% CI 0.29-0.99), p trend = 0.037. Intake of peanuts and tree nuts separately
      was also inversely related to ER - breast cancer subtypes, while no associations
      were found with peanut butter intake. CONCLUSIONS: Our findings suggest an
      inverse association between nut intake and ER - breast cancer, and no association
      with total or hormone receptor-positive subtypes.

PMID- 29168063
TI  - Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy
      predicts poor prognosis in estrogen receptor-positive/HER2-negative breast
      cancers.
AB  - PURPOSE: The therapeutic effect of systemic treatment for breast cancer (BC)
      generally depends on its intrinsic subtypes. In addition, tumor infiltrating
      lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage
      and disease prognosis. High TILs at baseline or after primary systemic
      chemotherapy are reported to be associated with better survival in triple
      negative or human epithelial growth factor receptor 2 (HER2)-positive BCs.
      However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2
      negative (ER+/HER2-) BC is still controversial. METHODS: We assessed TIL score
      (low, intermediate, and high) before and after primary systemic chemotherapy in
      every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47
      triple-negative, 58 HER2+ and 91 ER+/HER2- BCs were used to assess TILs before
      treatment. To assess TILs after treatment, we examined residual invasive
      carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80
      ER+/HER2- BCs. RESULTS: A high TIL score in triple-negative BC before treatment
      resulted in a significantly higher proportion of pathological complete response
      (pCR). In contrast, ER+/HER2- BC exhibited fewer instances of pCR than other
      subtypes. Although not statistically significant, ER+/HER2- cases with a high TIL
      score also tended to achieve pCR (p = 0.088). Moreover, we revealed that low TIL
      BCs after chemotherapy, but not at baseline, had significantly better relapse
      free survival in ER+/HER2- BC (p = 0.034). CONCLUSION: Pathological examination
      of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2- BC.

PMID- 29168064
TI  - Adipose tissue inflammation in breast cancer survivors: effects of a 16-week
      combined aerobic and resistance exercise training intervention.
AB  - PURPOSE: Obesity is a leading modifiable contributor to breast cancer mortality
      due to its association with increased recurrence and decreased overall survival
      rate. Obesity stimulates cancer progression through chronic, low-grade
      inflammation in white adipose tissue, leading to accumulation of adipose tissue
      macrophages (ATMs), in particular, the pro-inflammatory M1 phenotype macrophage.
      Exercise has been shown to reduce M1 ATMs and increase the more anti-inflammatory
      M2 ATMs in obese adults. The purpose of this study was to determine whether a 16
      week exercise intervention would positively alter ATM phenotype in obese
      postmenopausal breast cancer survivors. METHODS: Twenty obese postmenopausal
      breast cancer survivors were randomized to a 16-week aerobic and resistance
      exercise (EX) intervention or delayed intervention control (CON). The EX group
      participated in 16 weeks of supervised exercise sessions 3 times/week.
      Participants provided fasting blood, dual-energy X-ray absorptiometry (DXA), and
      superficial subcutaneous abdominal adipose tissue biopsies at baseline and
      following the 16-week study period. RESULTS: EX participants experienced
      significant improvements in body composition, cardiometabolic biomarkers, and
      systemic inflammation (all p < 0.03 vs. CON). Adipose tissue from EX participants
      showed a significant decrease in ATM M1 (p < 0.001), an increase in ATM M2 (p <
      0.001), increased adipose tissue secretion of anti-inflammatory cytokines such as
      adiponectin, and decreased secretion of the pro-inflammatory cytokines IL-6 and
      TNF- alpha (all p < 0.055). CONCLUSIONS: A 16-week aerobic and resistance
      exercise intervention attenuates adipose tissue inflammation in obese
      postmenopausal breast cancer survivors. Future large randomized trials are
      warranted to investigate the impact of exercise-induced reductions in adipose
      tissue inflammation and breast cancer recurrence.

PMID- 29168065
TI  - Are VNTRs co-localizing with breast cancer-associated SNPs?
AB  - PURPOSE: Several common genetic variants (single-nucleotide polymorphisms, SNPs)
      have been shown to be associated with breast cancer (BC) risk in the general
      population, and to modify BC risk for BRCA1 and BRCA2 mutation carriers. Co
      localization of variable number of tandem repeats (VNTRs) with these BC
      associated SNPS has not been comprehensively studied. METHODS: Cross referencing
      of genome-wide VNTRs with the known BC genome-wide association studies (GWAS)
      SNPs significantly associated with increased risk for developing breast cancer
      was carried out. Analysis was based on the overlap between the VNTRs and 10-kb
      windows around these BC-susceptibility SNPs. RESULTS: Cross referencing of the
      1.2 million TR with the 161 known BC-associated SNPs in the general population
      led to 690 matches. Of those, in 17 VNTRs, the SNP was within the VNTR. Analysis
      restricted to loci known to modify BC penetrance in BRCA1 (n = 31) and BRCA2 (n =
      33) mutation carriers led to 139 and 170 co-localization matches, respectively.
      For these, none of the SNPs were within the VNTR. The distances between the SNPs
      and the VNTRs were not significantly different from what was expected to occur by
      chance alone (p = 0.61; p = 0.44; p = 0.25, respectively). CONCLUSION: There is
      no evidence that VNTRs co-localize with currently reported SNP tagged BC GWAS
      loci.

PMID- 29168066
TI  - Changes in Anxiety and Depression Symptoms Predict Sexual Risk Behaviors Among
      Young Men Living in Dar es Salaam, Tanzania.
AB  - Young men are important targets in HIV prevention in Tanzania and throughout sub
      Saharan Africa. Anxiety and depression are common among youth and may be
      important predictors of HIV risk behaviors; evidence of these relationships in
      high-risk populations is needed. Using baseline and 1 year follow-up assessments
      from an HIV prevention trial we assessed the association between changes in
      symptoms of anxiety and depression and follow-up sexual risk behaviors (condom
      use and sexual partner concurrency) controlling for baseline sexual risk
      behaviors among 1113 male members of social groups known as "camps" in Dar es
      Salaam, Tanzania. Anxiety and depression were measured using the HSCL-25 and
      condom use and sexual partner concurrency were assessed through self-report. In
      separate models, increases in anxiety and depression were associated with sexual
      partner concurrency and with lower levels of condom use. In a combined model,
      both anxiety and depression appeared to independently affect concurrency but only
      depression was independently associated with condom use, with the association
      between anxiety and condom use being likely attributable to covariance with
      depression symptoms. The results of this study indicate the importance of
      screening and providing treatment for depression and anxiety disorders in high
      HIV-prevalence contexts, and the need to develop effective HIV prevention
      interventions targeting young men living with anxiety and depression.

PMID- 29168067
TI  - Continued Transmission of HIV Among Young Adults Who Inject Drugs in San
      Francisco: Still Room for Improvement.
AB  - We measured HIV incidence rate, trend and risk factors in 564 HIV-negative young
      people (< 30 years) who inject drugs (PWID) in San Francisco between 2000 and
      2014. HIV incidence was 0.93/100 person-years (PY; 95% CI 0.50, 1.73). Incidence
      varied between 0.62/100 PY in 2000-2002 and 1.06/100 PY in 2012-2014 (P for trend
      = 1.0). HIV incidence varied significantly (P < 0.01) by race/ethnicity: among
      Hispanics it was 8.19/100 PY (95% CI 3.41, 19.68), African-Americans 4.59/100 PY
      (95% CI 1.15, 18.37), and Whites 0.26/100 PY (95% CI 0.06, 1.03). Male
      participants who reported sex with men (MSM) had higher HIV incidence (2.63/100
      PY; 95% CI 1.31, 5.25) compared to males who did not report MSM (0.50/100 PY; 95%
      CI 0.12, 1.99) (P = 0.01). Despite an overall stable HIV incidence trend,
      incidence was elevated among African-American and Hispanic PWID, and men who have
      sex with men. Addressing prevention needs in these key populations is critical
      for the goal of eliminating HIV transmission.

PMID- 29168068
TI  - Predicting Arrest in a Sample of Youth Perinatally Exposed to HIV: The
      Intersection of HIV and Key Contextual Factors.
AB  - We examined the role of youth HIV status and other key factors on past-year
      arrest in perinatally HIV-exposed but uninfected (PHIV-) and perinatally HIV
      infected (PHIV+) youth using data from a multi-site study of psychosocial
      behaviors in PHIV-exposed urban youth (N = 340; 61% PHIV+; 51% female; ages 9-16
      at baseline). Youth and caregivers were administered 5 interviews, spanning
      approximately 7.5 years. Using longitudinal logistic mixed-effect models, we
      explored the association between past year arrest, internal [e.g., substance use
      disorder (SUD)] and external (e.g., neighborhood arrest rates) contextual
      factors, and social-regulation processes (e.g., in-school/work). Arrest rates
      increased from 2.6 to 19.7% across follow-ups; there were no differences in
      arrest over time by HIV status. In the final model, odds of arrest were greater
      for youth who were male, with SUD, >= 18 years old, with high levels of city
      stress, and neither in school nor employed. PHIV-exposed, urban youth have much
      higher rates of arrest than national samples. Lack of differences in arrest by
      HIV status suggests key contextual factors are more important in promoting
      arrest.

PMID- 29168069
TI  - Sexual Stigma Patterns Among Nigerian Men Who Have Sex with Men and Their Link to
      HIV and Sexually Transmitted Infection Prevalence.
AB  - Sexual stigma facilitates the spread of HIV and sexually transmitted infections
      (STIs) but little is known about stigma affecting Nigerian men who have sex with
      men (MSM). We assessed patterns of sexual stigma across Nigerian MSM and their
      relationship to HIV and STIs. Data were collected from the TRUST/RV368 Study, a
      prospective cohort of 1480 Nigerian MSM enrolled from March 2013 to February 2016
      using respondent driven sampling. Structural equation modeling was utilized to
      assess the association between stigma classes and HIV and STI prevalence,
      adjusting for participants' characteristics. A dose-response association was
      found between stigma class and HIV prevalence (27, 40, 55%, overall chi2 p <
      0.001) and STI prevalence (15, 21, 24%, overall chi2 p = 0.011). These data
      suggest that stigma mitigation strategies, combined with increased engagement of
      MSM and retention in the HIV care continuum, need to be a component of
      interventions focused on reducing HIV transmission risks among MSM in Nigeria.

PMID- 29168070
TI  - Arterial pulse attenuation prediction using the decaying rate of a pressure wave
      in a viscoelastic material model.
AB  - The present study examines the possibility of attenuating blood pulses by means
      of introducing prosthetic viscoelastic materials able to absorb energy and damp
      such pulses. Vascular prostheses made of polymeric materials modify the
      mechanical properties of blood vessels. The effect of these materials on the
      blood pulse propagation remains to be fully understood. Several materials for
      medical applications, such as medical polydimethylsiloxane or
      polytetrafluoroethylene, show viscoelastic behavior, modifying the original
      vessel stiffness and affecting the propagation of blood pulses. This study
      focuses on the propagation of pressure waves along a pipe with viscoelastic
      materials using the Maxwell and the Zener models. An expression of exponential
      decay has been obtained for the Maxwell material model and also for low viscous
      coefficient values in the Zener model. For relatively high values of the viscous
      term in the Zener model, the steepest part of the pulse can be damped quickly,
      leaving a smooth, slowly decaying wave. These mathematical models are critical to
      tailor those materials used in cardiovascular implants to the mechanical
      environment they are confronted with to repair or improve blood vessel function.

PMID- 29168071
TI  - Influence of functionally graded pores on bone ingrowth in cementless hip
      prosthesis: a finite element study using mechano-regulatory algorithm.
AB  - Cementless hip prostheses with porous outer coating are commonly used to repair
      the proximally damaged femurs. It has been demonstrated that stability of
      prosthesis is also highly dependent on the bone ingrowth into the porous texture.
      Bone ingrowth is influenced by the mechanical environment produced in the callus.
      In this study, bone ingrowth into the porous structure was predicted by using a
      mechano-regulatory model. Homogenously distributed pores (200 and 800 [Formula:
      see text]m in diameter) and functionally graded pores along the length of the
      prosthesis were introduced as a porous coating. Bone ingrowth was simulated using
      25 and 12 [Formula: see text]m micromovements. Load control simulations were
      carried out instead of traditionally used displacement control. Spatial and
      temporal distributions of tissues were predicted in all cases. Functionally
      graded pore decreasing models gave the most homogenous bone distribution, the
      highest bone ingrowth (98%) with highest average Young's modulus of all tissue
      phenotypes approximately 4.1 GPa. Besides this, the volume of the initial callus
      increased to 8.33% in functionally graded pores as compared to the 200 [Formula:
      see text]m pore size models which increased the bone volume. These findings
      indicate that functionally graded porous surface promote bone ingrowth
      efficiently which can be considered to design of surface texture of hip
      prosthesis.

PMID- 29168072
TI  - Estimates for the acoustical stimulation and heating of multiphase biotissue.
AB  - Low-intensity, unfocused, ultrasound-induced diathermy can produce undesired
      temperature increases at the interface of adjacent tissues within the body;
      particularly, at the interface of soft tissue and bone. This study provides a
      computational framework for predicting an upper bound on the temperature profile
      within a multiphase system composed of gel pad (water), tissue and bone from an
      input of acoustic energy, at frequencies and power levels consistent with
      applications of therapeutic hyperthermia. The model consists of solving a (one
      dimensional) spatially discretized bioheat transfer equation via finite
      difference method and updating the solution in time with a forward-Euler scheme.
      Simulations are then compared to experimental data to determine the energy-to
      heat conversion factors within each constituent material using thermocouple
      embedded, tissue-mimicking phantom material, with and without bone. Viscous
      heating artifacts from the presence of the thermocouples in the experimental
      phantom tissue are accounted for via additional experimental methods similar to
      those described by Morris et al. (Phys Med Biol 53:4759, 2008). Finally, an
      example application of the model is presented via prediction of the maximum
      temperature at the tissue-bone interface, as well as the peak temperatures in the
      composite structure at the end of a prescribed 2-min sonication, of blood
      perfused, human soft-tissue at 1, 2 and 3 MHz frequencies and a spatial peak
      temporally averaged intensity of [Formula: see text]. The results of this
      simulation are then related to comparable experimental studies in the literature.

PMID- 29168074
TI  - Paleoanthropology's uses of the bipedal criterion.
AB  - Bipedalism is one of the criteria that paleoanthropologists use in order to
      interpret the fossil record and to determine if a specimen belongs to the human
      lineage. In the context of such interpretations, bipedalism is considered to be a
      unique characteristic of this lineage that also marks its origin. This conception
      has largely remained unchallenged over the last decades, in spite of fossil
      discoveries that led to the emergence of bipedalism in the human lineage being
      shifted back by several millions of years. In this paper, I analyze the uses of
      this criterion in paleoanthropology and demonstrate that interpretative biases
      (such as underdetermined inferences and circular reasoning) are at play in
      interpretations of hominin remains. By discussing Darwin's hypotheses about the
      evolution of bipedalism, I identify major theoretical issues that need to be
      addressed in the current debates on hominin evolution. First, the assumption that
      "man alone has become a biped" (Darwin in The descent of man, and selection in
      relation to sex, John Murray, London, 1871) is analyzed in the light of recent
      empirical data. Three major issues are discussed: the definition of "man", i.e.
      "human", the uniqueness of human bipedalism, and the equivocal meaning of being a
      "biped". Then, I highlight some of Darwin's remarks that may be helpful for
      current debates in paleoanthropology, regarding natural selection in locomotor
      evolution, as well as taxonomic and phylogenetic significance of functional
      features. Finally, I analyze two examples of how fossil discoverers referred to
      Darwin in the recent years and discuss his role as an intellectual support.

PMID- 29168073
TI  - Fungus-Specific CD4 T Cells as Specific Sensors for Identification of Pulmonary
      Fungal Infections.
AB  - Patients with cystic fibrosis (CF) suffer from chronic lung infections, caused by
      bacterial, viral or fungal pathogens, which determine morbidity and mortality.
      The contribution of individual pathogens to chronic disease and acute lung
      exacerbations is often difficult to determine due to the complex composition of
      the lung microbiome in CF. In particular, the relevance of fungal pathogens in CF
      airways remains poorly understood due to limitations of current diagnostics to
      identify the presence of fungal pathogens and to resolve the individual host
      pathogen interaction status. T-lymphocytes play an essential role in host defense
      against pathogens, but also in inappropriate immune reactions such as allergies.
      They have the capacity to specifically recognize and discriminate the different
      pathogens and orchestrate a diverse array of effector functions. Thus, the
      analysis of the fungus-specific T cell status of an individual can in principle
      provide detailed information about the identity of the fungal pathogen(s)
      encountered and the actual fungus-host interaction status. This may allow to
      classify patients, according to appropriate (protective) or inappropriate
      (pathology-associated) immune reactions against individual fungal pathogens.
      However, T cell-based diagnostics are currently not part of the clinical routine.
      The identification and characterization of fungus-specific T cells in health and
      disease for diagnostic purposes are associated with significant challenges.
      Recent technological developments in the field of fungus-specific T helper cell
      detection provide new insights in the host T cell-fungus interaction. In this
      review, we will discuss basic principles and the potential of T cell-based
      diagnostics, as well as the perspectives and further needs for use of T cells for
      improved clinical diagnostics of fungal diseases.

PMID- 29168076
TI  - Model-Based Methods in the Biopharmaceutical Process Lifecycle.
AB  - Model-based methods are increasingly used in all areas of biopharmaceutical
      process technology. They can be applied in the field of experimental design,
      process characterization, process design, monitoring and control. Benefits of
      these methods are lower experimental effort, process transparency, clear
      rationality behind decisions and increased process robustness. The possibility of
      applying methods adopted from different scientific domains accelerates this trend
      further. In addition, model-based methods can help to implement regulatory
      requirements as suggested by recent Quality by Design and validation initiatives.
      The aim of this review is to give an overview of the state of the art of model
      based methods, their applications, further challenges and possible solutions in
      the biopharmaceutical process life cycle. Today, despite these advantages, the
      potential of model-based methods is still not fully exhausted in bioprocess
      technology. This is due to a lack of (i) acceptance of the users, (ii) user
      friendly tools provided by existing methods, (iii) implementation in existing
      process control systems and (iv) clear workflows to set up specific process
      models. We propose that model-based methods be applied throughout the lifecycle
      of a biopharmaceutical process, starting with the set-up of a process model,
      which is used for monitoring and control of process parameters, and ending with
      continuous and iterative process improvement via data mining techniques.

PMID- 29168075
TI  - Pharmacogenetics of Methadone Response.
AB  - The efficacy of methadone maintenance treatment (MMT) in opioid use disorder is
      well established but responses vary. The influence of methadone pharmacodynamics
      and pharmacokinetics on dose requirements and program outcomes remains
      controversial despite the increasing number of studies evaluating genetic
      influences on response to methadone treatment. Furthermore, patients require
      different doses (usually between 60 and 100 mg/day), and there are no clear data
      on a plasma concentration associated with treatment success. We review the
      evidence regarding the influence of genetics on pharmacokinetic and
      pharmacodynamic factors in terms of MMT outcome. We also analyse the influence of
      genetics on the occurrence of severe adverse events such as respiratory
      depression and ventricular arrhythmia in methadone treatment. The outcomes of MMT
      may be influenced by a combination of environmental, drug-induced, and genetic
      factors. The influence of pharmacokinetic genetic variability can be clinically
      managed by modifying the posology. A better understanding of pharmacodynamic
      factors could help in selecting the best opioid for substitution treatment, but
      patient phenotype must still be considered when establishing a maintenance
      treatment. Pharmacogenetic studies represent a promising field that aims to
      individualize treatments according to genetic backgrounds, adapting medication
      and doses according to possible outcomes and the risk of adverse events.

PMID- 29168077
TI  - Progress and challenges of sequencing and analyzing circulating tumor cells.
AB  - Circulating tumor cells (CTCs) slough off primary tumor tissues and are swept
      away by the circulatory system. These CTCs can remain in circulation or colonize
      new sites, forming metastatic clones in distant organs. Recently, CTC analyses
      have been successfully used as effective clinical tools to monitor tumor
      progression and prognosis. With advances in next-generation sequencing (NGS) and
      single-cell sequencing (SCS) technologies, scientists can obtain the complete
      genome of a CTC and compare it with corresponding primary and metastatic tumors.
      CTC sequencing has been successfully applied to monitor genomic variations in
      metastatic and recurrent tumors, infer tumor evolution during treatment, and
      examine gene expression as well as the mechanism of the epithelial-mesenchymal
      transition. However, compared with cancer biopsy sequencing and circulating tumor
      DNA sequencing, the sequencing of CTC genomes and transcriptomes is more complex
      and technically difficult. Challenges include enriching pure tumor cells from a
      background of white blood cells, isolating and collecting cells without damaging
      or losing DNA and RNA, obtaining unbiased and even whole-genome and transcriptome
      amplification material, and accurately analyzing CTC sequencing data. Here, we
      review and summarize recent studies using NGS on CTCs. We mainly focus on CTC
      genome and transcriptome sequencing and the biological and potential clinical
      applications of these methodologies. Finally, we discuss challenges and future
      perspectives of CTC sequencing.

PMID- 29168078
TI  - The effect of hypergastrinemia following sleeve gastrectomy and pantoprazole on
      type 2 diabetes mellitus and beta-cell mass in Goto-Kakizaki rats.
AB  - PURPOSE: Metabolic surgery alters the secretion of gastrointestinal hormones that
      influence glycemic control. Elevated gastrin has been suggested to benefit
      patients with type 2 diabetes and has been reported following sleeve gastrectomy
      in rats. The present study compares the effect of hypergastrinemia following
      sleeve gastrectomy with proton-pump inhibitor therapy on glycemic control and
      beta-cell mass in lean, diabetic animals. METHODS: Thirty-three diabetic Goto
      Kakizaki rats were randomized into pantoprazole + sham operation (GK-PPI), sleeve
      gastrectomy (GK-SG) and vehicle + sham operation (GK-V). Body weight, glucose
      parameters, HbA1c, glucagon-like peptide 1, gastrin, insulin and lipids were
      evaluated for eighteen postoperative weeks. Total beta-cell mass was quantified
      by optical projection tomography. RESULTS: After surgery, body weight development
      was equal among groups (P g = 0.75). Fasting and stimulated gastrin increased for
      GK-PPI and GK-SG vs. GK-V (p < 0.05 for all). Fasting blood glucose was decreased
      for GK-PPI and GK-SG vs. GK-V (p < 0.05 and p = 0.052). HbA1c was lower for GK-SG
      vs. GK-V at 6 weeks and for GK-PPI vs. GK-V at twelve- and eighteen weeks
      postoperative (p < 0.05 for all); a borderline difference was observed for GK-SG
      vs. GK-V at 18 weeks (p = 0.054). Total- and LDL cholesterol was elevated for GK
      PPI compared to the other two groups (p < 0.05 for all). Beta-cell mass did not
      differ among groups (p = 0.35). CONCLUSIONS: Hypergastrinemia following sleeve
      gastrectomy and pantoprazole has a similar, modest effect on glycemic control in
      Goto-Kakizaki rats but does not enhance beta-cell mass after 18 weeks.
      Hypergastrinemia in the setting of T2DM might be of clinical relevance.

PMID- 29168079
TI  - Use of Mixture Designs to Investigate Contribution of Minor Sex Pheromone
      Components to Trap Catch of the Carpenterworm Moth, Chilecomadia valdiviana.
AB  - Field experiments were carried out to study responses of male moths of the
      carpenterworm, Chilecomadia valdiviana (Lepidoptera: Cossidae), a pest of tree
      and fruit crops in Chile, to five compounds previously identified from the
      pheromone glands of females. Previously, attraction of males to the major
      component, (7Z,10Z)-7,10-hexadecadienal, was clearly demonstrated while the role
      of the minor components was uncertain due to the use of an experimental design
      that left large portions of the design space unexplored. We used mixture designs
      to study the potential contributions to trap catch of the four minor pheromone
      components produced by C. valdiviana. After systematically exploring the design
      space described by the five pheromone components, we concluded that the major
      pheromone component alone is responsible for attraction of male moths in this
      species. The need for appropriate experimental designs to address the problem of
      assessing responses to mixtures of semiochemicals in chemical ecology is
      described. We present an analysis of mixture designs and response surface
      modeling and an explanation of why this approach is superior to commonly used,
      but statistically inappropriate, designs.

PMID- 29168080
TI  - Cardioprotective Effects of Morroniside in Rats Following Acute Myocardial
      Infarction.
AB  - The aim of this study is to investigate the cardioprotective effects of
      morroniside in rats following acute myocardial infarction. An acute myocardial
      infarction (AMI) was induced by ligating the anterior descending coronary artery
      (LAD) [1]. Following AMI, morroniside was administered intragastrically for 24 h
      at doses of 45, 90, and 180 mg/kg, respectively. Biomarkers such as creatine
      kinase (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase
      (alpha-HBDH), and aspartate aminotransferase (AST) activities in AMI rats in the
      serum were detected with commercial kits [2]. Following AMI, morroniside was
      administered intragastrically for 72 h at doses of 45, 90, and 180 mg/kg/d,
      respectively. The expression of nuclear factor kappa B (NF-kappaB) in cardiac
      myocardium was detected by western blotting analysis. Meanwhile, cardiac function
      was measured by echocardiography. We observed morroniside decreased the levels of
      CK-MB, LDH, alpha-HBDH, and AST activities in AMI rats after 24 h. We also found
      that morroniside reduced the expression of NF-kappaB in cardiac myocardium at 72
      h post AMI rats. Further, cardiac function was improved by administration of
      morroniside. Collectively, our findings demonstrated that morroniside had
      cardioprotective effects in rats following acute myocardial infarction.
      Attenuation of inflammation might contribute to the cardioprotective effects of
      morroniside.

PMID- 29168081
TI  - High Glucose Stimulates Expression of MFHAS1 to Mitigate Inflammation via Akt/HO
      1 Pathway in Human Umbilical Vein Endothelial Cells.
AB  - Hyperglycemia is a highly dangerous factor to various diseases, even resulting in
      death of people. Inflammation plays a key role in this process. The aim of this
      study was to explore the role of malignant fibrous histiocytoma amplified
      sequence 1 (MFHAS1) in high-glucose induced inflammation. Our research showed
      that high glucose stimulated the expression of MFHAS1, and overexpression of
      MFHAS1 can attenuate high-glucose induced inflammation in endothelial cells by
      decreasing the secretion of cytokines interleukin-1beta (IL-1beta), interleukin
      1alpha (IL-1alpha), adhesion molecule intercellular adhesion molecule-1 (ICAM),
      interleukin-6 (IL-6), interleukin-8 (IL-8), and chemokine ligand 1 (CXCL-1).
      Furthermore, we found that MFHAS1 promoted the phosphorylation of Akt and the
      expression of heme oxygenase-1 (HO-1). Our results indicated that MFHAS1 deadened
      high-glucose induced inflammation by activating AKT/HO-1 pathway, suggesting that
      MFHAS1 may act as a new therapeutic target of diabetes mellitus.

PMID- 29168083
TI  - Analysis of the cancer genome atlas (TCGA) database identifies an inverse
      relationship between interleukin-13 receptor alpha1 and alpha2 gene expression
      and poor prognosis and drug resistance in subjects with glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. A
      variety of targeted agents are being tested in the clinic including cancer
      vaccines, immunotoxins, antibodies and T cell immunotherapy for GBM. We have
      previously reported that IL-13 receptor subunits alpha1 and alpha2 of IL-13R
      complex are overexpressed in GBM. We are investigating the significance of IL
      13Ralpha1 and alpha2 expression in GBM tumors. In order to elucidate a possible
      relationship between IL-13Ralpha1 and alpha2 expression with severity and
      prognoses of subjects with GBM, we analyzed gene expression (by microarray) and
      clinical data available at the public The Cancer Genome Atlas (TCGA) database
      (Currently known as Global Data Commons). More than 40% of GBM samples were
      highly positive for IL-13Ralpha2 mRNA (Log2 >= 2) while only less than 16%
      samples were highly positive for IL-13Ralpha1 mRNA. Subjects with high IL
      13Ralpha1 and alpha2 mRNA expressing tumors were associated with a significantly
      lower survival rate irrespective of their treatment compared to subjects with IL
      13Ralpha1 and alpha2 mRNA negative tumors. We further observed that IL-13Ralpha2
      gene expression is associated with GBM resistance to temozolomide (TMZ)
      chemotherapy. The expression of IL-13Ralpha2 gene did not seem to correlate with
      the expression of genes for other chains involved in the formation of IL-13R
      complex (IL-13Ralpha1 or IL-4Ralpha) in GBM. However, a positive correlation was
      observed between IL-4Ralpha and IL-13Ralpha1 gene expression. The microarray data
      of IL-13Ralpha2 gene expression was verified by RNA-Seq data. In depth analysis
      of TCGA data revealed that immunosuppressive genes (such as FMOD, CCL2, OSM,
      etc.) were highly expressed in IL-13Ralpha2 positive tumors, but not in IL
      13Ralpha2 negative tumors. These results indicate a direct correlation between
      high level of IL-13R mRNA expression and poor patient prognosis and that
      immunosuppressive genes associated with IL-13Ralpha2 may play a role in tumor
      progression. These findings have important implications in understanding the role
      of IL-13R in the pathogenesis of GBM and potentially other cancers.

PMID- 29168082
TI  - A pilot study of neuropsychological functions, APOE and amyloid imaging in
      patients with gliomas.
AB  - Brain tumor patients treated with radiotherapy (RT) often develop cognitive
      dysfunction, and recent studies suggest that the APOE epsilon-4 allele may
      influence cognitive outcome. The epsilon-4 allele is known to promote beta (beta)
      amyloid deposition in the cortex, and preliminary evidence suggests that RT may
      be associated with this process. However, it is unknown whether beta-amyloid
      accumulation contributes to treatment neurotoxicity. In this pilot study, we
      assessed neuropsychological functions and beta-amyloid retention using 18F
      florbetaben (FBB) PET in a subset of brain tumor patients who participated in our
      study of APOE polymorphisms and cognitive functions. Twenty glioma patients
      treated with conformal RT +/- chemotherapy participated in the study: 6 were APOE
      epsilon-4 carriers and 14 were non-epsilon-4 carriers. Patients completed a
      neuropsychological re-evaluation (mean time interval = 5 years, SD = 0.83) and
      brain MRI and FBB PET scans. Wilcoxon signed-rank test comparisons between prior
      and current neuropsychological assessments showed a significant decline in
      attention (Brief Test of Attention, p = 0.018), and a near significant decline in
      verbal learning (Hopkins Verbal learning Test-Learning, p = 0.07). Comparisons by
      APOE status showed significant differences over time in attention/working memory
      (WAIS-III digits forward, p = 0.028 and digits backward, p = 0.032), with a
      decline among APOE epsilon-4 carriers. There were no significant differences in
      any of the FBB PET analyses between APOE epsilon-4 carriers and non-epsilon-4
      carriers. The findings suggest that glioma patients may experience worsening in
      attention and executive functions several years after treatment, and that the
      APOE epsilon-4 allele may modulate cognitive decline, but independent of
      increased beta-amyloid deposition.

PMID- 29168084
TI  - Bioinformatic analysis of gene expression and methylation regulation in
      glioblastoma.
AB  - Different gene expression and methylation profiles are identified in glioblastoma
      (GBM). To screen the differentially expressed genes affected by DNA methylation
      modification and further investigate their prognostic values for GBMs. We
      included The Cancer Genome Atlas (TCGA) RNA sequencing (676) and DNA methylation
      (Illumina Human Methylation 450K; 657) databases to detect the gene expression
      and methylation profiles. Chinese Glioma Genome Atlas (CGGA) RNA sequencing
      database and TCGA DNA methylation (Illumina Human Methylation 27K; 283) was
      included for validation. Gene expression and DNA methylation statues were
      identified using principal components analysis (PCA). A total of 3365
      differentially expressed genes were identified. Among them, 2940 genes showed low
      methylation and high expression, while 425 genes showed high methylation and low
      expression in GBMs. An eight-gene (C9orf64, OSMR, MDK, MARVELD1, PTRF, MYD88,
      BIRC3, RPP25) signature was established to divide GBM patients into two groups
      based on the cut-off point (27.24). The high risk group had shorter overall
      survival (OS) than low risk group (median OS 15.77 vs. 10.61 months; P = 0.0002).
      Moreover, the different clinical and molecular features were shown between two
      groups. These findings could be validated in additional datasets. The
      differentially expressed genes affected by DNA methylation modification were
      detected. Our results showed that the eight-gene signature has independently
      prognostic value for GBM patients.

PMID- 29168085
TI  - Prevalence of Human Papillomavirus Genotypes and Abnormal Pap Smears Among Women
      in the Military Health System.
AB  - Human papillomavirus infection (HPV) is the most common sexually transmitted
      infection among United States Military Servicemembers, and present in the
      majority of cervical cancers. Many of these infections are preventable, but HPV
      immunization is not mandatory during military service. The objective of this
      study was to examine the prevalence of vaccine-preventable cervical disease among
      women enrolled in the San Antonio Military Health System. This is a retrospective
      cross-sectional study of Pap smear results and HPV genotyping data among Military
      Servicewomen and beneficiaries. Simple descriptive statistics and logistic
      regression were used to assess the association between demographics, cervical
      pathology and high-risk HPV (hrHPV) infection. Pap smears were obtained by 16.9%
      of women and cervical pathology was present in 28.8% of samples. Compared to the
      25-34 year group, 35-44 year-olds were more likely to have an abnormal Pap smear
      (OR 1.25, CI 1.05-1.50). Of the samples tested, 10.5% were positive for hrHPV.
      Adjusted multivariable analysis revealed that hrHPV infection was more likely
      among the 23-34 year group when compared to 35-44 (OR 0.50, CI 0.38-0.67), 45-54
      (0.40. CI 0.28-0.59) and 55-65 year groups (0.46, CI 0.30-0.71). Active Duty
      Servicewomen were more likely to test positive for hrHPV when compared to Active
      Duty Family Members (OR 0.59, CI 0.45-0.79) and Retiree Family Members (OR 0.59,
      CI 0.41-0.83). Younger women and Active Duty Servicewomen are significantly more
      likely to have cervical infection with hrHPV. Future studies should assess the
      cost-effectiveness of mandatory HPV immunization for military members.

PMID- 29168086
TI  - Increased white matter metabolic rates in autism spectrum disorder and
      schizophrenia.
AB  - Both autism spectrum disorder (ASD) and schizophrenia are often characterized as
      disorders of white matter integrity. Multimodal investigations have reported
      elevated metabolic rates, cerebral perfusion and basal activity in various white
      matter regions in schizophrenia, but none of these functions has previously been
      studied in ASD. We used 18fluorodeoxyglucose positron emission tomography to
      compare white matter metabolic rates in subjects with ASD (n = 25) to those with
      schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of
      stereotaxically placed regions-of-interest. Both subjects with ASD and
      schizophrenia showed increased metabolic rates across the white matter regions
      assessed, including internal capsule, corpus callosum, and white matter in the
      frontal and temporal lobes. These increases were more pronounced, more widespread
      and more asymmetrical in subjects with ASD than in those with schizophrenia. The
      highest metabolic increases in both disorders were seen in the prefrontal white
      matter and anterior limb of the internal capsule. Compared to normal controls,
      differences in gray matter metabolism were less prominent and differences in
      adjacent white matter metabolism were more prominent in subjects with ASD than in
      those with schizophrenia. Autism spectrum disorder and schizophrenia are
      associated with heightened metabolic activity throughout the white matter. Unlike
      in the gray matter, the vector of white matter metabolic abnormalities appears to
      be similar in ASD and schizophrenia, may reflect inefficient functional
      connectivity with compensatory hypermetabolism, and may be a common feature of
      neurodevelopmental disorders.

PMID- 29168087
TI  - Mediating Parent Learning to Promote Social Communication for Toddlers with
      Autism: Effects from a Randomized Controlled Trial.
AB  - A randomized controlled trial was conducted to evaluate effects of the Joint
      Attention Mediated Learning (JAML) intervention. Toddlers with autism spectrum
      disorders (ASD) aged 16-30 months (n = 144) were randomized to intervention and
      community control conditions. Parents, who participated in 32 weekly home-based
      sessions, followed a mediated learning process to target preverbal social
      communication outcomes (social visual synchrony, reciprocity, and responding and
      initiating forms of joint attention) throughout daily interactions. The analysis
      found post-intervention effects for all outcomes, with all except initiating
      joint attention sustaining 6 months post-intervention. Findings support the value
      of very early intervention targeting explicitly social functions of preverbal
      communication and of promoting active engagement in the learning process for both
      toddlers and parents.

PMID- 29168088
TI  - What Are You Doing With That Object? Comparing the Neural Responses of Action
      Understanding in Adolescents With and Without Autism.
AB  - Understanding another's actions, including what they are doing and why they are
      doing it, can be difficult for individuals with autism spectrum disorder (ASD).
      This understanding is supported by the action observation (AON) and mentalizing
      (MZN) networks, as well as the superior temporal sulcus. We examined these areas
      in children with ASD and typically developing controls by having participants
      view eating and placing actions performed in conventional and unconventional ways
      while functional magnetic resonance images were collected. We found an effect of
      action-type, but not conventionality, in both groups, and a between groups
      difference only when viewing conventional eating actions. Findings suggest there
      are not global AON/MZN deficits in ASD, and observing unconventional actions may
      not spontaneously activate the MZN.

PMID- 29168089
TI  - Brief Report: Investigating Relations Between Self-Concept and Performance in
      Reading and Math for School-Aged Children and Adolescents with Autism Spectrum
      Disorder.
AB  - A typically developing student's perceptions of his or her own capabilities
      (academic self-concept), is predictive of later academic achievement. However,
      little is known about academic self-concept in youth with autism spectrum
      disorder (ASD). To understand whether students math self-concept and reading self
      concept predicted their performance, 44 school-aged children and adolescents with
      ASD and 36 age-matched individuals with typical development (TYP) rated their
      perceived math and reading abilities and were administered standardized
      achievement measures. Results showed self-concept was predictive of performance
      in math and reading in the TYP group. For youth with ASD, there was agreement
      between self-concept and performance only in math. These findings suggest that
      educators should be cautious when interpreting the self-assessments of reading
      ability in students with ASD.

PMID- 29168090
TI  - Using Virtual Interactive Training Agents (ViTA) with Adults with Autism and
      Other Developmental Disabilities.
AB  - Conversational virtual human (VH) agents are increasingly used to support role
      play experiential learning. This project examined whether a Virtual Interactive
      Training Agent (ViTA) system would improve job interviewing skills in individuals
      with autism and developmental disabilities (N = 32). A linear mixed model was
      employed to evaluate adjusted least square mean differences of means scores on
      the Marino Interview Assessment Scale (MIAS) across different time points. The
      mean score of MIAS over all questions increased between the first ViTA session
      and the final face-to-face interview. Participants developed the ability to
      identify strengths, self-promote, self-advocate, answer situational questions,
      and respond to behavioral/social questions as measured by multiple evaluations
      using the MIAS.

PMID- 29168091
TI  - Postural and Cortical Responses Following Visual Occlusion in Adults With and
      Without ASD.
AB  - Autism is associated with differences in sensory processing and motor
      coordination. Evidence from electroencephalography suggests individual
      perturbation evoked response (PER) components represent specific aspects of
      postural disturbance processing; P1 reflects the detection and N1 reflects the
      evaluation of postural instability. Despite the importance of these cortical
      responses to postural control, PERs to a perturbation in adults with autism
      spectrum disorder (ASD) have yet to be reported. The aim was to compare PERs to
      visual perturbation under varied postural stability conditions in adults with and
      without ASD. This study is the first to report that while the assessment of
      postural set is intact, adults with ASD use more cortical resources to integrate
      and interpret visual perturbations for postural control.

PMID- 29168093
TI  - Application of two-dimensional binary fingerprinting methods for the design of
      selective Tankyrase I inhibitors.
AB  - In the present study, five important binary fingerprinting techniques were used
      to model novel flavones for the selective inhibition of Tankyrase I. From the
      fingerprints used: the fingerprint atom pairs resulted in a statistically
      significant 2D QSAR model using a kernel-based partial least square regression
      method. This model indicates that the presence of electron-donating groups
      positively contributes to activity, whereas the presence of electron withdrawing
      groups negatively contributes to activity. This model could be used to develop
      more potent as well as selective analogues for the inhibition of Tankyrase I.
      Schematic representation of 2D QSAR work flow.

PMID- 29168092
TI  - Propofol Prevents Oxidative Stress by Decreasing the Ischemic Accumulation of
      Succinate in Focal Cerebral Ischemia-Reperfusion Injury.
AB  - Oxidative stress caused by mitochondrial dysfunction during reperfusion is a key
      pathogenic mechanism in cerebral ischemia-reperfusion (IR) injury. Propofol (2,6
      diisopropylphenol) has been proven to attenuate mitochondrial dysfunction and
      reperfusion injury. The current study reveals that propofol decreases oxidative
      stress injury by preventing succinate accumulation in focal cerebral IR injury.
      We evaluated whether propofol could attenuate ischemic accumulation of succinate
      in transient middle cerebral artery occlusion in vivo. By isolating mitochondria
      from cortical tissue, we also examined the in vitro effects of propofol on
      succinate dehydrogenase (SDH) activity and various mitochondrial bioenergetic
      parameters related to oxidative stress injury, such as the production of reactive
      oxidative species, membrane potential, Ca2+-induced mitochondrial swelling, and
      morphology via electron microscopy. Propofol significantly decreased the ischemic
      accumulation of succinate by inhibiting SDH activity and inhibited the oxidation
      of succinate in mitochondria. Propofol can decrease membrane potential in normal
      mitochondria but not in ischemic mitochondria. Propofol prevents Ca2+-induced
      mitochondrial swelling and ultrastructural changes to mitochondria. The
      protective effect of propofol appears to act, at least in part, by limiting
      oxidative stress injury by preventing the ischemic accumulation of succinate.

PMID- 29168094
TI  - What Money Can't Buy: Different Patterns in Decision Making About Sex and Money
      Predict Past Sexual Coercion Perpetration.
AB  - Self-reported impulsivity has been found to predict the perpetration of sexual
      coercion in both sexual offenders and male college students. Impulsivity can be
      conceptualized as a generalized lack of self-control (i.e., general perspective)
      or as a multifaceted construct that can vary from one context to the other (i.e.,
      domain-specific perspective). Delay discounting, the tendency to prefer sooner
      smaller rewards over larger delayed rewards, is a measure of impulsive decision
      making. Recent sexual adaptations of delay discounting tasks can be used to test
      domain-specific assumptions. The present study used the UPPS-P impulsivity
      questionnaire, a standard money discounting task, and a sexual discounting task
      to predict past use of sexual coercion in a sample of 98 male college students.
      Results indicated that higher negative urgency scores, less impulsive money
      discounting, and more impulsive sexual discounting all predicted sexual coercion.
      Consistent with previous studies, sexuality was discounted more steeply than
      money by both perpetrators and non-perpetrators of sexual coercion, but this
      difference was twice as large in perpetrators compared to non-perpetrators. Our
      study identified three different predictors of sexual coercion in male college
      students: a broad tendency to act rashly under negative emotions, a specific
      difficulty to postpone sexual gratification, and a pattern of optimal non-sexual
      decision making. Results highlight the importance of using multiple measures,
      including sexuality-specific measures, to get a clear portrait of the links
      between impulsivity and sexual coercion.

PMID- 29168095
TI  - Comment on: Sentinel Node Biopsy Using Magnetic Tracer Versus Standard Technique:
      The SentiMAG Multicentre Trial.

PMID- 29168096
TI  - Anti-VEGF Therapy in the Treatment of Unresectable Appendiceal Epithelial
      Neoplasms.

PMID- 29168097
TI  - Comment: Fancier and More Expensive Do Mean Better: An Argument for Computed
      Tomography Staging of Patients With Colorectal Liver Metastases.

PMID- 29168098
TI  - Proposal of a New Preoperative Prognostic Model for Solitary Hepatocellular
      Carcinoma Incorporating 18F-FDG-PET Imaging with the ALBI Grade.
AB  - BACKGROUND: Existing prognostic systems were not developed using only objective
      variables available preoperatively, and therefore do not provide ideal
      prognostication for patients undergoing hepatectomy for hepatocellular carcinoma
      (HCC). We aimed to develop a preoperative prognostic model using objective
      variables involving two parameters: 18F-fluorodeoxyglucose-positron emission
      tomography (18F-FDG-PET) and the albumin-bilirubin (ALBI) grade. METHODS: This
      study included 207 consecutive patients with solitary HCC who underwent 18F-FDG
      PET prior to hepatectomy. The tumor to non-tumor maximum standardized uptake
      value ratio (TNR) was used as an 18F-FDG PET imaging parameter. RESULTS: The 5
      year overall survival (OS) and disease-free survival (DFS) rates were 58.6% and
      28.8%, respectively. Multivariate analysis of OS identified TNR >= 2 (hazard
      ratio [HR] 1.743, 95% confidence interval [CI] 1.114-2.648, p = 0.016) and ALBI
      grade 2 (HR 1.966, 95% CI 1.349-2.884, p < 0.001) as the only significant
      prognostic factors; tumor diameter and tumor markers were not significant.
      Patients were divided into low- (TNR < 2 and ALBI grade 1), intermediate- (TNR <
      2 and ALBI grade 2, or TNR >= 2 and ALBI grade 1), and high-risk (TNR >= 2 and
      ALBI grade 2) groups, which differed significantly in terms of survival (5-year
      OS: 75.7, 49.6, and 27.3%, respectively, p < 0.001; 5-year DFS: 37.0, 24.9, and
      13.6%, respectively, p < 0.001). Compared with other staging systems, our model
      had the best discriminatory ability (corrected Akaike information criteria
      1054.8, p < 0.001) and homogeneity (likelihood ratio Chi square value 27.6, p <
      0.001). CONCLUSION: A preoperative prognostic model incorporating 18F-FDG-PET
      imaging with the ALBI grade may be useful for estimating the prognosis of
      selected patients with solitary HCC.

PMID- 29168101
TI  - Letters to the Editor Anthology: An e-Supplement Resource.

PMID- 29168099
TI  - Benchmarking the American Society of Breast Surgeon Member Performance for More
      Than a Million Quality Measure-Patient Encounters.
AB  - BACKGROUND: Nine breast cancer quality measures (QM) were selected by the
      American Society of Breast Surgeons (ASBrS) for the Centers for Medicare and
      Medicaid Services (CMS) Quality Payment Programs (QPP) and other performance
      improvement programs. We report member performance. STUDY DESIGN: Surgeons
      entered QM data into an electronic registry. For each QM, aggregate "performance
      met" (PM) was reported (median, range and percentiles) and benchmarks (target
      goals) were calculated by CMS methodology, specifically, the Achievable Benchmark
      of CareTM (ABC) method. RESULTS: A total of 1,286,011 QM encounters were captured
      from 2011-2015. For 7 QM, first and last PM rates were as follows: (1) needle
      biopsy (95.8, 98.5%), (2) specimen imaging (97.9, 98.8%), (3) specimen
      orientation (98.5, 98.3%), (4) sentinel node use (95.1, 93.4%), (5) antibiotic
      selection (98.0, 99.4%), (6) antibiotic duration (99.0, 99.8%), and (7) no
      surgical site infection (98.8, 98.9%); all p values < 0.001 for trends.
      Variability and reasons for noncompliance by surgeon for each QM were identified.
      The CMS-calculated target goals (ABCTM benchmarks) for PM for 6 QM were 100%,
      suggesting that not meeting performance is a "never should occur" event.
      CONCLUSIONS: Surgeons self-reported a large number of specialty-specific patient
      measure encounters into a registry for self-assessment and participation in QPP.
      Despite high levels of performance demonstrated initially in 2011 with minimal
      subsequent change, the ASBrS concluded "perfect" performance was not a realistic
      goal for QPP. Thus, after review of our normative performance data, the ASBrS
      recommended different benchmarks than CMS for each QM.

PMID- 29168102
TI  - Comment on: Global Cancer Consortiums: Moving from Consensus to Practice.

PMID- 29168103
TI  - Amputation for Extremity Sarcoma: Contemporary Indications and Outcomes.
AB  - INTRODUCTION: Amputation for localized extremity sarcoma (ES), once the primary
      therapy, is now rarely performed. We reviewed our experience to determine why
      patients with sarcoma still undergo immediate or delayed amputation, identify
      differences based on amputation timing, and evaluate outcomes. METHODS: Records
      of patients with primary, nonmetastatic ES who underwent amputation at our
      institution from 2001 to 2011 were reviewed. Univariate analysis was performed,
      and survival outcomes were calculated. RESULTS: We categorized 54 patients into
      three cohorts: primary amputation (A1, n = 18, 33%), secondary amputation after
      prior limb-sparing surgery (A2, n = 22, 41%), and hand and foot sarcomas (HF, n =
      14, 26%). Median age at amputation was 54 years (range 18-88 years). Common
      indications for amputation (> 40%) were loss of function, bone involvement,
      multiple compartment involvement, and large tumor size (A1); proximal location,
      joint involvement, neurovascular compromise, multiple compartment involvement,
      multifocal or fungating tumor, loss of function, and large tumor size (A2); and
      joint involvement and prior unplanned surgery (HF). There was no difference in
      disease-specific survival (DSS) (p = 0.19) or metastasis-free survival (MFS) (p =
      0.31) between early (A1) and delayed (A2) amputation. Compared with cohorts
      A1/A2, HF patients had longer overall survival (OS) (p = 0.04). CONCLUSIONS:
      Indications for amputation for extremity sarcoma vary between those who undergo
      primary amputation, delayed amputation, and amputation for hand or foot sarcoma.
      Amputations chosen judiciously are associated with excellent disease control and
      survival. For patients who ultimately need amputation, timing (early vs. delayed)
      does not affect survival.

PMID- 29168104
TI  - Safe use of infliximab for the treatment of severe perianal Crohn's disease after
      diagnosis and treatment of lymphoma.
AB  - Inflammatory bowel disease is associated with an increased likelihood of
      developing lymphoma. However, it is still controversial if this risk may be
      attributed to the disease itself or rather represents an effect of
      immunosuppressive treatment. Although tumor necrosis factor alpha (TNFalpha) is a
      key cytokine for cancer immunosurveillance, the potential relationship between
      anti-TNFalpha agents and the pathogenesis of lymphoproliferative disorders
      remains unclear. Here, we describe the case of a patient with severe perianal
      Crohn's disease, treated with infliximab monotherapy, whose unusual presentation
      with acute groin pain required surgical intervention and led to the diagnosis of
      diffuse large B-cell lymphoma. However, 10 months after this episode, treatment
      with infliximab was restarted because the patient continued with refractory and
      disabling perianal disease. Currently, with a follow-up of 36 months, under
      infliximab 10 mg/kg every 4 weeks, he maintains mild perianal Crohn's disease and
      persists in sustained clinical and imaging remission of the lymphoproliferative
      disorder.

PMID- 29168105
TI  - Evaluation of four commercial natural products for repellency and toxicity
      against the lone star tick, Amblyomma americanum (Acari: Ixodidae).
AB  - Lone star ticks are aggressive ectoparasites of domestic and wild animals, as
      well as humans. These ticks can transmit many pathogens that cause disease
      including Erhlichia and tularemia. Common compounds used for personal protection
      and area sprays are N-diethyl-3-methyl benzamide (DEET) and permethrin, but
      public concern over personal and environmental safety require the development of
      new, safer products. In the current study, four commercially available products
      (Wondercide, Essentria IC3, Vet's Best, and Mosquito Barrier) were tested for
      both repellent and toxic effects against lone star tick nymphs and adults.
      Overall, all four products were more effective against nymphs than against
      adults. Wondercide and Essentria IC3 were as toxic to nymphs as permethrin at
      concentrations of 3.13% and higher, and as repellent as DEET at all
      concentrations. Nymphs were also repelled by Mosquito Barrier and Vet's Best, but
      these products had about half or less of the repellent effects of Wondercide and
      Essentria IC3 at most of the concentrations. Adult ticks were repelled similarly
      by all products at all tested concentrations, but at lower levels than nymphs.
      Toxicity of the four tested products on adults was similar at concentrations of
      12.5% and below, less than half of what was observed with permethrin with
      declining effectiveness as concentrations decreased. Overall, these four products
      may offer a natural way to repel lone star ticks, but further field testing is
      needed to determine rates of application and residual activity.

PMID- 29168106
TI  - Effects of Exercise on Depression and Anxiety. A Comparison to Transdiagnostic
      Cognitive Behavioral Therapy.
AB  - The aims of this study were (i) to know the effects of an exercise program on a
      group of people with depression and anxiety and (ii) to compare theses effects
      with a transdiagnostic cognitive behavioral group therapy (TCBGT). The
      participants were 15 people with depression and/or anxiety symptoms. The
      participants followed an exercise program. Depression and anxiety symptoms were
      assessed with validated questionnaires. An exercise program can be used as a
      treatment option for people with depression and/or anxiety with good results in
      comparison with TCBGT.

PMID- 29168107
TI  - Predictive factors of trastuzumab-based chemotherapy in HER2 positive advanced
      gastric cancer: a single-center prospective observational study.
AB  - PURPOSE: Trastuzumab plus chemotherapy is an effective therapy in HER2 positive
      advanced gastric cancer (AGC). However, the clinicopathologic factors that
      predict the outcome of routine trastuzumab therapy remain unclear. METHODS: The
      outcome and safety profile of trastuzumab therapy in untreated HER2 positive AGC
      was evaluated in this prospective observational study. Clinical and pathological
      data including demographics, treatment profiles, expression level of HER2 were
      analyzed to identify predictive factors of trastuzumab-based first-line therapy
      for their progression-free survival (PFS). RESULTS: Overall, 107 patients were
      eligible. The median number of treatment cycles was 9 (range 1-44), the median
      PFS and median overall survival (OS) were 7.7 months (95% CI 6.5-8.9) and 16.0
      months (95% CI 13.2-18.8), respectively. The confirmed response rate was 58.9%,
      and the disease control rate was 82.2%. Patients with liver metastasis (HR 1.616)
      and poor performance status (PS, HR 2.518) were independently associated with a
      worse PFS, while the other clinicopathological factors including demographics,
      treatment profiles and some other clinical characteristics did not predict the
      survival. CONCLUSIONS: In routine clinical practice, the addition of trastuzumab
      to chemotherapy was effective and safe in real-world setting in Chinese patients
      with HER2 positive AGC, regardless of most of the clinicopathological factors.
      Further studies are needed to improve the prognosis of HER2 positive patients
      with liver metastasis or poor PS. Trial Registration clinicaltrials.gov
      Identifier: NCT03024450.

PMID- 29168108
TI  - The malaris muscle: its morphological significance for sustaining the
      intraorbital structures.
AB  - The orbicularis oculi muscle, an important mimetic muscle, was investigated to
      ascertain its anatomical relation to facial aging-especially its orbital part
      (Oo). Previous studies of the distinct muscle bundles frequently found inferior
      to the Oo have provided various definitions, including that of the malaris
      muscle. This study aimed to examine these muscle bundles and clarify their
      function in facial aging. Twelve heads of Japanese cadavers (average age: 82.5
      years old) were dissected to observe the muscles, focusing in particular on those
      in the periorbital region. Six specimens were further dissected from the inner
      surfaces to examine the patterns of facial nerve branches under the operating
      microscope. Histological examinations of two head halves were carried out to
      investigate the relationship between the muscle bundles and the intraorbital
      structures. Muscle bundles consisting of lateral, medial, and U-shaped suspending
      bundles were observed in the region inferior to the Oo. Lateral and suspending
      bundles were found in all specimens, while the medial bundles were noted in only
      9 of 22 specimens. Some branches of the facial nerve penetrated through the
      lateral, medial, and suspending bundles. The relationship between the suspending
      bundles and the protruding orbital fat was assessed. The muscle bundles found in
      this study were regarded as the malaris muscle-a transitional muscle between the
      superficial and deep facial layers. The suspending bundle may play a role in
      sustaining the intraorbital structures.

PMID- 29168109
TI  - A Case of Glomangiopericytoma at the Nasal Septum.
AB  - Glomangiopericytoma (GPC) is a rare sinonasal perivascular tumor that accounts
      for < 0.5-1% of all sinonasal tumors. GPC is categorized as a low-grade neoplasm
      with borderline malignancy and a tendency of local recurrence. GPC is a rare
      mesenchymal neoplasm characterized by the perivascular proliferation of tumor
      cells, and it requires being distinguished from solitary fibrous tumors. Here, we
      report a case of GPC in a 68-year-old male patient who presented at the emergency
      room of our hospital with a complaint of sudden epistaxis. A small, reddish,
      protruding tumor was observed on the right nasal septum. A biopsy revealed a
      possible perivascular tumor such as a GPC or solitary fibrous tumor. Thus, we
      performed complete resection with endoscopic surgery. The size of the resected
      tumor was 12 * 5 mm, and it showed a uniform proliferation of oval-to-short
      spindle-shaped cells with slightly branching vascular structures. The tumor cells
      showed minimal cytologic atypia and there were an average of 3 mitoses in 10 high
      power fields. Necrosis was not observed. The tumor cells showed strong and
      diffuse nuclear immunostaining with beta catenin and were negative with STAT6,
      CD34 and bcl-2. The MIB-1 labeling index was approximately 5%. Genetic testing
      revealed CTNNB1 mutation (p.S33C). Thus, a diagnosis of low grade GPC was made on
      the biopsy and the patient could be successfully treated with endoscopic
      resection.

PMID- 29168110
TI  - Symptom covariance accounts for behavioral approach associations across impulse
      control disorders.
AB  - Behavioral approach system (BAS) dysfunction has been identified as a correlate
      of and a potential mechanism for attention-deficit/hyperactivity disorder (ADHD)
      and comorbid disorders. This study examined the role of symptom covariation in
      the relations among BAS dysfunction, ADHD symptoms, and comorbid impulsive
      personality disorder features. Undergraduates (N = 207) completed measures of BAS
      functioning, ADHD symptoms, and borderline and antisocial personality disorder
      symptoms, and associated features (i.e., relational aggression). Hierarchical
      regression suggested that age, impulsive ADHD symptoms, and relational aggression
      were associated with BAS functioning. Adding other ADHD symptom dimensions
      (inattention, hyperactivity) and antisocial and borderline scores to the model
      did not increase variance accounted for beyond that accounted for by ADHD
      impulsivity scores. Results highlight a role of symptom covariance in the
      previously demonstrated relation between BAS, impulsive presentations of ADHD,
      and comorbid impulsive personality pathology. Implications for etiological models
      of ADHD and its co-occurrence with other disorders are discussed.

PMID- 29168111
TI  - Bariatric Surgery and Time to Total Joint Arthroplasty: Does It Affect
      Readmission and Complication Rates?
AB  - BACKGROUND: Bariatric surgery is frequently recommended prior to total joint
      arthroplasty (TJA) for morbidly obese patients with end-stage arthropathy.
      Current published data on the efficacy of bariatric surgery for preoperative
      medical optimization has yielded mixed results, and the effect of time from
      bariatric surgery to TJA on the preoperative risk profile is not well defined.
      Our study evaluated the effect of time from bariatric surgery to TJA on 90-day
      complication and readmission rates. METHODS: We utilized the Healthcare Cost and
      Utilization Project (HCUP) California State Inpatient Database (SID) to identify
      patients who underwent TJA following bariatric surgery between 2007 and 2011.
      Primary endpoints were 90-day complication rates and all-cause 90-day readmission
      rates following TJA. RESULTS: We identified 330 cases of bariatric surgery
      followed by total hip arthroplasty (THA) and 1017 cases followed by total knee
      arthroplasty (TKA). There were no significant demographic differences among
      patients who underwent TJA greater than or less than 6 months after bariatric
      surgery. Patients undergoing THA more than 6 months after bariatric surgery were
      significantly less likely to be readmitted within 90 days for any cause. There
      was no association between time from bariatric surgery to THA or TKA and 90-day
      complications. DISCUSSION: Delaying THA at least 6 months after bariatric surgery
      may help reduce the rate of 90-day readmissions in this high-risk patient
      population. Arthroplasty surgeons recommending bariatric surgery as preoperative
      risk modification should consider the patient's overall nutritional status,
      medical comorbidities, and overall response to surgery prior to booking for TJA.

PMID- 29168112
TI  - Treatment Patterns and Outcomes in Patients with KRAS Wild-Type Metastatic
      Colorectal Cancer Treated in First Line with Bevacizumab- or Cetuximab-Containing
      Regimens.
AB  - PURPOSE: Patients with Kirsten rat sarcoma viral oncogene wild-type (KRAS WT)
      metastatic colorectal cancer (mCRC) treated in first line with bevacizumab (B) or
      cetuximab (C) plus standard chemo backbones had comparable outcomes in phase III
      Cancer and Leukemia Group B (CALGB) 80405. We examined comparative effectiveness
      of B and C regimens in real-world community settings. METHODS: This retrospective
      study examined progression-free survival (PFS) and OS in a US community sample of
      KRAS WT mCRC patients treated with first-line B (n = 254) or C (n = 146)
      regimens. Medical records from the Vector Oncology Data Warehouse were used.
      Disease progression was determined from patient charts. OS was measured from the
      start of first-line treatment until death. RESULTS: There were no significant
      difference in either PFS or OS respectively between B-treated compared to C
      treated patients (HR = 1.324, 95% CI 0.901, 1.947; HR = 1.080, 95% CI 0.721,
      1.617). More B patients received oxaliplatin backbones (74.8 vs. 36.3%), and more
      C patients received irinotecan backbones (51.4 vs. 20.1%), ps < 0.001.
      Multivariate survival analyses showed a significant difference indicating a
      greater risk for death among C-treated patients with right-sided tumors vs. left
      sided tumors (HR = 2.263, 95% CI 1.394, 3.673, p = 0.0009), but not for B-treated
      patients (HR = 1.209, 95% CI 0.825, 1.771, p = 0.3297). CONCLUSIONS: Consistent
      with CALGB 80405, median PFS and OS for these community oncology KRAS WT mCRC
      patients treated with first-line B or C regimens did not differ significantly.

PMID- 29168113
TI  - Dynamics of Bone Marrow VSELs and HSCs in Response to Treatment with Gonadotropin
      and Steroid Hormones, during Pregnancy and Evidence to Support Their
      Asymmetric/Symmetric Cell Divisions.
AB  - Gender plays an important role in the incidence of hematological malignancies and
      recently hematopoietic stem cells (HSCs) were found to proliferate more in
      females that gets further augmented during pregnancy. It was suggested that since
      basal numbers of HSCs remain the same in both sexes, possibly HSCs in females
      undergo increased self-renewal and apoptosis. Then how is self-renewal of stem
      cells regulated in males? More important, do HSCs undergo asymmetric cell
      divisions (ACD) or a more primitive population of pluripotent, very small
      embryonic-like stem cells (VSELs) undergo ACD to self-renew and specify into
      HSCs? Lot more clarity is required on the bone marrow stem cells biology. Present
      study was undertaken to evaluate whether similar dimorphism reported for HSCs
      also exists among VSELs. Bone marrow VSELs and HSCs were studied in bilaterally
      ovariectomized and castrated mice by flow cytometry after treating with
      gonadotropin (FSH) and sex steroid (estrogen & progesterone) hormones and during
      pregnancy. Differential expression of pluripotent (Oct-4A, Sox2, Nanog) and
      differentiation (Oct-4, Sca1, c-Kit, Ikaros) specific transcripts was studied.
      Basal BrdU uptake was more in both VSELs (p < 0.01) and HSCs (p < 0.05) in female
      bone marrow. FSH exerted a more profound effect compared to estradiol in both the
      sexes. Flow cytometry results showed ten-fold increase in spleen VSELs by mid
      gestation associated with approximately two-fold increase in HSCs. These results
      point to a novel yet unreported role of spleen VSELs during pregnancy.
      Furthermore, VSELs underwent ACD to self-renew and give rise to slightly bigger
      HSCs based on unequal expression of NUMB, CD45 and OCT-4.

PMID- 29168115
TI  - Semantic Ambiguity Effects in L2 Word Recognition.
AB  - The present study examined the ambiguity effects in second language (L2) word
      recognition. Previous studies on first language (L1) lexical processing have
      observed that ambiguous words are recognized faster and more accurately than
      unambiguous words on lexical decision tasks. In this research, L1 and L2 speakers
      of English were asked whether a letter string on a computer screen was an English
      word or not. An ambiguity advantage was found for both groups and greater
      ambiguity effects were found for the non-native speaker group when compared to
      the native speaker group. The findings imply that the larger ambiguity advantage
      for L2 processing is due to their slower response time in producing adequate
      feedback activation from the semantic level to the orthographic level.

PMID- 29168114
TI  - Parathyroid hormone in surgery-induced weight loss: no glucometabolic effects but
      potential adaptive response to skeletal loading.
AB  - PURPOSE: Increased parathyroid hormone (PTH) is commonly associated with obesity,
      and its role in the pathogenesis of obesity-related glucometabolic abnormalities
      is uncertain. We aimed to explore the relationships of PTH with glucose/insulin
      homeostasis parameters before and after bariatric surgery-induced weight loss,
      and whether they depend or not on 25-hydroxyvitamin D (25OHD) status. METHODS: We
      included 42 subjects (27 women, aged 40 +/- 5 years, BMI 48.5 +/- 7.3 kg/m2)
      without diabetes, chronic kidney disease, or hyperparathyroidism undergoing
      sleeve gastrectomy. The following parameters were evaluated before and 6 months
      after surgery: circulating levels of PTH, calcium, phosphorus, 25OHD, leptin,
      insulin growth factor (IGF)-1; 75-g oral glucose tolerance test to derive
      measures of insulin sensitivity (ISI) and secretion (Stumvoll index); dual-energy
      X-ray absorptiometry to assess fat distribution and bone mineral density.
      RESULTS: Weight loss was accompanied by significant reduction of PTH levels (77.9
      +/- 19.1 vs. 60.5 +/- 13.4 pg/ml; p = 0.005), without concomitant modification of
      25OHD status. Both baseline PTH and its postoperative percent change resulted
      associated, with baseline fat mass (beta = 0.615, p = 0.003) and its concurrent
      postoperative reduction (r = 0.419; p = 0.006), but neither with glucose
      homeostasis parameters nor their respective variations after weight loss.
      Interestingly, leptin reduction after weight loss was independently related to
      PTH change (beta = 0.396, p = 0.015) and IGF-1 levels (beta = 0.176, p = 0.059).
      CONCLUSIONS: Circulating PTH decreases with fat mass reduction independent of
      25OHD status, but it  is not associated with improvement of insulin resistance
      and related metabolic parameters. Leptin and PTH may mediate the cross-talk
      between adipose tissue and parathyroid glands, which possibly contributes to bone
      adaptation to excess body weight.

PMID- 29168116
TI  - Reference to Self and Other in the Digital Public Sphere: The Case of Political
      Blogs.
AB  - In this paper, we analyze how a political blog author (Spanish Alejo Vidal
      Quadras) establishes the reference to self and other in his blog entries. We
      furthermore look into how the commentators to this blog react and establish
      reference to self and other in the digital public sphere. More concretely, we
      show that they not only take up the references established by the main blog
      author but also create new references. These allow, on the one hand, for
      profiling themselves as part of a group and, on the other hand, identifying their
      interlocutor among the variety of possible interlocutors in the digital public
      sphere. By addressing different interlocutors, the commentators turn the comments
      section into a dialogic space, a dimension that is lacking in the main blog
      entries. However, the fact that they almost invariably identify interlocutors
      other than Vidal-Quadras but address Vidal-Quadras without explicitly identifying
      him, shows that Vidal-Quadras remains the main ratified interlocutor in view of
      his ownership of the blog. This paper shows then how participants in the digital
      public sphere create a complex relationship of self and other reference in
      political blogs.

PMID- 29168117
TI  - Anaphoric Strategies Across Language Modalities: A Comparison Between Catalan and
      Catalan Sign Language (LSC).
AB  - The goal of this paper is to compare the different anaphoric strategies that
      Catalan and Catalan Sign Language (LSC) use by means of a parallel corpus. In
      particular, our comparison is focused in an examination of the uses of overt
      subject pronouns in Catalan and how these uses are rendered in a language that
      exploits the visual-manual modality, such as LSC. As far as we know, this is one
      of the first studies to compare reference-tracking devices in a spoken and a
      signed language by means of a parallel corpus and incorporating both a
      descriptive and a theoretical perspective. All instances of overt pronouns in
      Catalan were analyzed and most of the data can be accounted with three factors:
      topic change, focus and contrast. As for LSC, the use of pronouns is rare and
      only few instances were found. Instead, other anaphoric strategies are used:
      while topic change and focus are primarily encoded with bare nouns, the
      expression of contrast relies on modality-specific features.

PMID- 29168118
TI  - Ion-protein interactions of a potassium ion channel studied by attenuated total
      reflection Fourier transform infrared spectroscopy.
AB  - An understanding of ion-protein interactions is key to a better understanding of
      the molecular mechanisms of proteins, such as enzymes, ion channels, and ion
      pumps. A potassium ion channel, KcsA, has been extensively studied in terms of
      ion selectivity. Alkali metal cations in the selectivity filter were visualized
      by X-ray crystallography. Infrared spectroscopy has an intrinsically higher
      structural sensitivity due to frequency changes in molecular vibrations
      interacting with different ions. In this review article, I attempt to summarize
      ion-exchange-induced differences in Fourier transform infrared spectroscopy, as
      applied to KcsA, to explain how this method can be utilized to study ion-protein
      interactions in the KcsA selectivity filter. A band at 1680 cm-1 in the amide I
      region would be a marker band for the ion occupancy of K+, Rb+, and Cs+ in the
      filter. The band at 1627 cm-1 observed in both Na+ and Li+ conditions suggests
      that the selectivity filter similarly interacts with these ions. In addition to
      the structural information, the results show that the titration of K+ ions
      provides quantitative information on the ion affinity of the selectivity filter.

PMID- 29168119
TI  - Clinical and biological significance of a - 73A > C variation in the CDH1
      promoter of patients with sporadic gastric carcinoma.
AB  - BACKGROUND: CDH1 germline mutations lead to hereditary diffuse gastric
      carcinomas. However, it is unclear whether genetic variations in the CDH1
      promoter affect the progression of sporadic gastric carcinomas (SGCs). METHODS:
      SGC patients in two independent cohorts with follow-up data were enrolled. The
      CDH1 genotypes, including the - 73A > C polymorphism (rs28372783), were
      determined by PCR sequencing. The CDH1 promoter activity was determined using
      reporter assays. SNAIL bound to CDH1 alleles was determined by chromatin
      immunoprecipitation primer extension PCR. CDH1 DNA methylation was determined by
      bisulfite-based PCR analyses. RESULTS: Kaplan-Meier analyses showed that the
      overall survival (OS) of the - 73C/C patients was significantly longer than that
      of the - 73A/C or - 73A/A patients in a Chinese cohort [n = 526; hazard ratio
      0.68 (95% CI 0.47-1.00)], which was validated in an independent Korea cohort [n =
      215; hazard ratio 0.49 (95% CI 0.26-0.94)]. Moreover, the transcription activity
      of the - 73C alleles was significantly higher than that of the - 73A alleles in
      vitro and in vivo. The ratio of SNAIL recruited to the promoter regions of the -
      73C and - 73A alleles was 1:10, indicating a strong influence of this
      polymorphism on the recruitment of SNAIL to the flanking E-box. The prevalence of
      DNA methylation of the CpG island and shore within the promoter of the - 73C
      allele was much less than that of the - 73A allele in both gastric tissues and
      cancer cell lines. CONCLUSION: The - 73A > C variation may lead to differences in
      the overall survival of SGC patients and allele-specific repressions of CDH1.

PMID- 29168121
TI  - Paradigm changes in freshwater aquaculture practices in China: Moving towards
      achieving environmental integrity and sustainability.
AB  - Contribution of fisheries and aquaculture to global food security is linked to
      increased fish consumption. Projections indicate that an additional 30-40 million
      tonnes of fish will be required by 2030. China leads global aquaculture
      production accounting for 60% in volume and 45% in value. Many changes in the
      Chinese aquaculture sector are occurring to strive towards attaining
      environmental integrity and prudent use of resources. We focus on changes
      introduced in freshwater aquaculture developments in China, the main source of
      food fish supplies. We bring forth evidence in support of the contention that
      Chinese freshwater aquaculture sector has introduced major paradigm changes such
      as prohibition of fertilisation in large water bodies, introduction of stringent
      standards on nutrients in effluent and encouragement of practices that strip
      nutrients among others, which will facilitate long-term sustainability of the
      sector.

PMID- 29168120
TI  - The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis
      staging system for gastric cancer is superior to the 7th edition: results from a
      Chinese mono-institutional study of 1663 patients.
AB  - BACKGROUND: We investigated the superiority of the 8th edition of the tumor-node
      metastasis (TNM) system for patients in China with gastric cancer. METHODS: The
      survival outcomes of 1663 patients with gastric cancer undergoing radical
      resection were analyzed. RESULTS: In the 8th edition system, homogeneous 5-year
      survival rates among different pathological TNM (pTNM) categories belonging to
      the same stage were observed. However, in the 7th edition system, the differences
      of 5-year survival rate among pTNM categories belonging to the same stage were
      observed in stages IIB (P = 0.010), IIIB (P = 0.004), and IIIC (P < 0.001). For
      patients in the pT1-3 (P < 0.001) and pT4a (P < 0.001) categories, there were
      significant differences in survival between patients in the pN3a and pN3b
      categories. Furthermore, partial cases (pT4bN0M0/T4aN2M0) of stage IIIB were
      downstaged to stage IIIA in the 8th edition system, and the 5-year survival rate
      of these patients was significantly better than that of patients in stage IIIB in
      the 8th edition system. Similarly, the 5-year survival rate of patients in
      p4bN2M0/T4aN3aM0 downstaged from stage IIIC to IIIB was significantly better than
      that of patients in stage IIIC. Compared with the 7th edition system, the 8th
      edition system had a higher likelihood ratio and linear trend chi-squared score
      and a smaller Akaike information criteria value. CONCLUSIONS: The 8th edition
      system is superior to the 7th edition system in terms of homogeneity,
      discriminatory ability, and monotonicity of gradients for Chinese patients with
      gastric cancer.

PMID- 29168122
TI  - Subtropical Interactions: Comparing Galling Insect and Host Plant Diversity in
      Southern Brazil and Florida.
AB  - Gall-inducing insects seem to have a diversity pattern distinct from the usual
      latitudinal decrease in species, with more species occurring in xeric
      environments instead. Many questions regarding galler diversity over geographical
      scales remain unanswered: for example, little is known about beta diversity, and
      the role super host plants play in local/regional richness. Our aim was to
      compare galling insect and host plant diversity in different biogeographical
      regions, but under similar environmental conditions. We sampled short stature
      coastal woodlands on sandy soils of the Atlantic coast in both USA (Florida) and
      Brazil (Rio Grande do Sul, RS), between 25 degrees  and 30 degrees  latitude.
      Little-used 200-m long trails were searched during 90 min for galls; there were
      four trails in USA and five in Brazil. Gall functional traits (galled plant
      organ, gall shape and colour) proportions were not different between Florida and
      RS. Local galling and host plant species richness also did not differ, and
      neither did regional galling diversity. The beta diversity pattern, however, was
      distinct: sites in Florida have more similar galling faunas than sites in RS.
      Common diversity patterns indicate common environmental biotic (plant diversity,
      vegetation structure) and abiotic (climate, soil) factors might be contributing
      to these similar responses. As Brazilian sites are in the Atlantic forest
      hotspot, a high galling insect beta diversity might be caused by a higher
      heterogeneity at larger scales-sample-based rarefaction curves were ascending for
      Brazil, but not for USA. Myrtaceans were super hosts in Brazil, but not in
      Florida, where oaks take up this role.

PMID- 29168123
TI  - Correction to: Norwegian reference values for the Short-Form Health Survey 36:
      development over time.
AB  - In the original publication of the article, the right number of participants
      included in the analysis should be 2107 and not 2118 as written in the paper. The
      flow-chart and corrected SF-36 scores for the 2015 data set for this article
      should have appeared as follows: Fig. 1 and Table 3. These changes did not
      influence the results. The authors would like to apologize for any inconvenience
      caused.

PMID- 29168124
TI  - In Vitro Inhibitory Activity of Acca sellowiana Fruit Extract on End Products of
      Advanced Glycation.
AB  - INTRODUCTION: Hyperglycemia plays an important role in the pathogenesis of
      diabetic complications, as it increases protein glycation, as well as the
      progressive accumulation of advanced glycation end products (AGEs), which are
      complex structures that produce fluorescence. The glycation reaction raises the
      levels of protein carbonyl, N epsilon-(carboxymethyl)lysine (CML), and
      fructosamine and decreases the level of thiol groups. METHODS: In the present
      study, the antiglycation activity was determined by fluorescence intensity using
      the bovine serum albumin (BSA)/glucose, CML method, and the level of
      fructosamine. The oxidation of proteins was determined by the carbonyl protein
      content and thiol groups. RESULTS: The results show that the hexane extract of
      Acca sellowiana (FOH) at different concentrations (0.30-5 mg/ml) significantly
      inhibited the formation of AGEs in the BSA/glucose model during the 4 weeks of
      the study. FOH reduced the levels of fructosamine and CML. Our results showed a
      significant effect of FOH in the prevention of oxidative damage of proteins, as
      well as an effect on the oxidation of thiol groups and carbonyl proteins.
      CONCLUSION: The present study indicates that FOH is effective in inhibiting the
      glycation of proteins in vitro, so it can prevent or ameliorate the chronic
      conditions of diabetes associated with the formation of AGEs.

PMID- 29168125
TI  - Some Questions Pondered on Health and Humanities: Prospects, Opportunities and
      Challenges.

PMID- 29168126
TI  - Do alerting signals increase the size of the attentional focus?
AB  - Previous research has shown that the presentation of an auditory alerting signal
      before a visual target increases the interference from flanking distractors.
      Recently, it has been suggested that this increase in interference may be due to
      an expansion of the spatial focus of attention. In five experiments, this
      hypothesis was tested by using a probe technique dedicated to measuring
      variations in the size of the attentional focus: In the majority of trials,
      participants performed a letter discrimination task in which their attention was
      focused on a central target letter. In a randomly intermixed probe task, the size
      of the attentional focus was measured by letting participants respond to a probe
      occurring at varying positions. In all experiments, reaction time (RT) to the
      probe increased from the most central to more lateral probe positions. This V
      shaped probe-RT function, however, was not flattened by the presentation of an
      alerting signal. Overall, this pattern of results is inconsistent with the
      hypothesis that alerting signals increase the attentional focus. Instead, it is
      consistent with nonspatial accounts that attribute the increase in interference
      to an alerting effect on perceptual processing, which then leads to a detrimental
      effect at the level of response selection.

PMID- 29168127
TI  - Bioavailability of Orally Administered Des-Aspartate-Angiotensin I in Human
      Subjects.
AB  - In an earlier single-dose escalation study to evaluate the safety and
      pharmacokinetics of orally administered des-aspartate-angiotensin I (DAA-I) in
      healthy subjects, the plasma level of DAA-I could not be determined because DAA-I
      is rapidly degraded in the circulation. The present study investigated the oral
      bioavailability of DAA-I by measuring the prostaglandin E2 metabolite (PGEM) in
      the plasma samples of the same trial. PGEM is a stable derivative of PGE2, which
      has been shown to be a biomarker of DAA-I. The data show that plasma from two of
      the three subjects who were orally administered the efficacious preclinical dose
      of 0.70 mg/kg DAA-I exhibited a significant PGEM peak at 5-6 h postdose. Plasma
      of subjects who were administered 0.08 and 1.5 mg/kg DAA-I, the subefficacious
      and two-times efficacious dose, respectively, did not exhibit a similar PGEM
      peak. This observation is concordant with the known in vivo actions of DAA-I,
      especially its hypoglycemic action where maximum efficacy occurred at a dose of
      0.7 mg/kg, and decreased to nil at the two-times efficacious dose. The onset of
      the PGEM peak at 5-6 h postdose was closed to the 4-h onset of absorption of
      [C14]DAA-I seen in preclinical rat studies, albeit the absorption kinetics
      between rodents and humans are not identical. The occurrence of polymorphism of
      enzymes involved in the formation and degradation of PGE2 is common, and this has
      been attributed to contributing to the variation in response, onset and peak PGEM
      observed among the three subjects who were administered the efficacious dose.

PMID- 29168128
TI  - Enhancement of Galantamine HBr Skin Permeation Using Sonophoresis and Limonene
      Containing PEGylated Liposomes.
AB  - This study aimed to investigate the effect of low-frequency sonophoresis (SN) and
      limonene-containing PEGylated liposomes (PL) on the transdermal delivery of
      galantamine HBr (GLT). To evaluate the skin penetration mechanism, confocal laser
      scanning microscopy (CLSM), Fourier transform infrared spectroscopy (FTIR), and
      differential scanning calorimetry (DSC) were employed. The application of SN led
      to more GLT penetration into and through the skin than GLT solution alone. The
      liposomes also improved GLT permeation, and 2% limonene-containing PL (PL-LI2%)
      exhibited the highest GLT permeation, followed by PL-LI1%, PL-LI0.1%, and PL. The
      CLSM images of PL-LI2% resulted in the highest fluorescence intensity of
      fluorescent hydrophilic molecules in the deep skin layer, and the rhodamine PE
      labeled liposome membrane was distributed in the intercellular region of the
      stratum corneum (SC). PL-LI2% induced significant changes in intercellular lipids
      in the SC, whereas SN had no effect on intercellular lipids of the SC. DSC
      thermograms showed that the greatest decrease in the lipid transition temperature
      occurred in PL-LI2%-treated SC. SN might improve drug permeation through an
      intracellular pathway, while limonene-containing liposomes play an important role
      in delivering GLT through an intercellular pathway by increasing the fluidity of
      intercellular lipids in the SC. Moreover, a small vesicle size and high membrane
      fluidity might enhance the transportation of intact vesicles through the skin.

PMID- 29168129
TI  - Flavone protects HBE cells from DNA double-strand breaks caused by PM2.5.
AB  - Ambient air particulate matter 2.5 (PM2.5) contains many harmful components that
      can enter the circulatory system and produce reactive oxygen species (ROS) in
      body. Oxidative stress and DNA damage induced by ROS may affect any cellular
      macromolecule and lead to DNA double-strand breaks (DSBs). Flavonoids, widely
      distributed in some herbs and berries, have been proved having anti-oxidative or
      anti-cancer efficacy. In this study, we investigated whether Flavone, a kind of
      flavonoids, can protect human bronchial epithelial cells (HBE) from DSBs caused
      by PM2.5 and how this function is probably implemented. We found that cells
      exposed to PM2.5 obviously induced viability inhibition, DNA damage and part of
      apoptosis. However, Flavone treatment prior to PM2.5 apparently improved cell
      viability, and mitigated the formation of 8-hydroxy-2-deoxyguanosine, the
      expression of DNA damage-relative protein and cell apoptosis. Our studies
      demonstrated that PM2.5 induced oxidative DSBs while Flavone ameliorated the DNA
      damage and increased cell viability probably through influencing DNA repair
      mechanism of cells.

PMID- 29168131
TI  - The Relationship Between Spiritual Intelligence and Aggression Among Elite
      Wrestlers in Hamadan Province of IRAN.
AB  - The purpose of this study was to investigate the relationship between spiritual
      intelligence and aggression among elite wrestlers of adolescent age group. The
      present study was descriptive of correlation type in terms of method and applied
      in terms of purpose. The population of this research was the elite wrestlers of
      adolescents age group aged 14-17 (mean and SD of 15.27 +/- 1.33) using the
      convenient sampling method for adolescent wrestling teams of Hamedan clubs
      selected as samples. To measure variables, King's spiritual intelligence scale
      and Bass and Perry aggression questionnaire were used. Pearson correlation
      coefficient and simple regression method were used for data analysis. Results
      showed a significant negative relationship between spiritual intelligence and
      aggression. The spiritual intelligence scores also have a significant effect on
      aggression. The findings show that the higher the spiritual intelligence, the
      less likely the aggression of the elite wrestlers in different competitions and
      they can have a better performance than others.

PMID- 29168130
TI  - Tolerance towards gentamicin is a function of nutrient concentration in biofilms
      of patient-isolated Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis is a biofilm-forming bacterial strain that can cause
      major problems as an agent of nosocomial infections. Bacteria in biofilms are
      shielded from the environment and can survive high doses of antibiotics. We here
      test the antibiotic susceptibility of Staphylococcus epidermidis to rising
      gentamicin concentrations in optimal growth conditions as used in routine
      bacteriology laboratories with low nutrient situations as suggested to be found
      in clinical situations. We found that gentamicin-resistant Staphylococcus
      epidermidis biofilms survived in the absence of external nutrient supply in PBS.
      While addition of gentamicin sulfate significantly reduced the pH value of all
      used media and solutions, this acidification did not alter survival of bacteria
      in the biofilm. We found a statistically significant and dose-dependent reduction
      of survival in low nutrient situations using gentamicin sulfate in three out of
      four patient isolates of Staphylococcus epidermidis which have been tested to be
      gentamicin-resistant under optimal growth conditions. Supporting the original
      profiling, survival in full media under the same antibiotic dosages was not
      significantly reduced. Our data here show that antibiotic resistance is a
      function of the provided nutrient concentration. Antibiotic resistance profiling
      should consider variations in nutrient availability.

PMID- 29168132
TI  - Heavy metals in the surface sediments of lakes on the Tibetan Plateau, China.
AB  - Heavy metal contamination has affected many regions in the world, particularly
      the developing countries of Asia. We investigated 8 heavy metals (Cu, Zn, Cd, Pb,
      Cr, Co, Ni, and As) in the surface sediments of 18 lakes on the Tibetan Plateau.
      It was found that the distributions of the heavy metals showed no clear spatial
      pattern on the plateau. The results indicated that the mean concentrations of
      these metals in the sediment samples diminished as follows: Cr > As > Zn > Ni >
      Pb > Cu > Co > Cd. The results of geoaccumulation index (I geo) and potential
      ecological risk factor (E ir ) assessments showed that the sediments were
      moderately polluted by Cd and As, which posed much higher risks than the other
      metals. The values of the potential ecological risk index (RI) showed that lake
      Bieruoze Co has been severely polluted by heavy metals. Principal component
      analysis, hierarchical cluster analysis, and Pearson correlation analysis results
      indicated that the 8 heavy metals in the lake surface sediments of the Tibetan
      Plateau could be classified into four groups. Group 1 included Cu, Zn, Pb, Co,
      and Ni which were mainly derived from both natural and traffic sources. Group 2
      included Cd which mainly originated from anthropogenic sources like alloying,
      electroplating, and dyeing industries and was transported to the Tibetan Plateau
      by atmospheric circulation. Group 3 included Cr and it might mainly generate from
      parent rocks of watersheds. The last Group (As) was mainly from manufacturing,
      living, and the striking deterioration of atmospheric environment of the West,
      Central Asia, and South Asia.

PMID- 29168133
TI  - Assessment of oral and lung bioaccessibility of Cd and Pb from smelter-impacted
      dust.
AB  - Soil and dust contamination by metals engenders significant environmental and
      health problems in northern France where a lead smelter was in activity for more
      than a century. This study aims to examine the long-term effects of the smelter,
      10 years after its closedown, on the presence of metal in sidewalk dust for a
      better assessment of the local population's exposure to Cd and Pb. The
      investigation included: (i) the metal distribution in different dust particle
      sizes and (ii) the assessment of metal bioaccessibility via ingestion and
      inhalation of dust. Seventy-two sidewalk dust samples were collected using a dust
      sampling vacuum. The samples were sieved to collect different particle sizes from
      0.3 to 1000 MUm. The unified bioaccessibility method (UBM) was employed to
      evaluate the oral bioaccessibility of metals in the different particle sizes. The
      pulmonary bioaccessible fraction of Cd and Pb via the finest particles was
      extracted with lung-simulating solution (artificial lysosomal fluid). Ten years
      after the smelter closedown, (i) a strong relationship was observed between the
      concentrations of metals in dust and the distance to the former smelter, whatever
      the particle size; (ii) both total and oral bioaccessible concentrations of
      metals were high in the finest fraction (0.3-5 MUm) and decreased when the
      particle size increased; (iii) a higher oral bioaccessibility of Cd and Pb was
      measured in the gastric phase (on average 43% for both metals for all particle
      sizes) and compared to the gastrointestinal phase (on average 16% for both metals
      for all particle sizes); and (iv) metal bioaccessibility via inhalation of dust
      was relatively high (on average 74 and 69%, for Cd and Pb, respectively). The
      results of the present study suggest that this environmental compartment may be a
      sensitive and effective indicator of anthropogenic metal contamination and the
      human exposure in urban areas.

PMID- 29168134
TI  - Effects of soil properties and aging process on the acute toxicity of cadmium to
      earthworm Eisenia fetida.
AB  - This study was undertaken to investigate the effects of soil properties and aging
      process on the acute toxicity of cadmium (Cd) to Eisenia fetida (E. fetida) in 18
      Cd-spiked soils. Results showed that the Cd toxicity to E. fetida differed in the
      18 soils with different characteristics, and median lethal concentration (LC50)
      values varied from 440.7 to 1520.4 mg/kg in freshly spiked soils. Soil pH and
      organic matter (OM) content were the two major factors associated with Cd
      toxicity. The increase in LC50 values and decreases in both exchangeable Cd in
      soils and tissue Cd concentrations in earthworm whole body indicated that aging
      (180 and 360 days) could reduce the acute toxicity and bioavailability of Cd to
      E. fetida. Cadmium concentrations in E. fetida were positively correlated with
      exchangeable Cd content in soils, and soil pH and OM were the key factors
      controlling the distribution and transformation of the exchangeable Cd. The
      results will provide useful reference information for the risk assessment of Cd
      in the terrestrial environment.

PMID- 29168135
TI  - Visible light-induced photocatalytic degradation of Reactive Blue-19 over highly
      efficient polyaniline-TiO2 nanocomposite: a comparative study with solar and UV
      photocatalysis.
AB  - Polyaniline-TiO2 (PANI-TiO2) nanocomposite was prepared by in situ polymerisation
      method. X-ray diffractogram (XRD) showed the formation of PANI-TiO2 nanocomposite
      with the average crystallite size of 46 nm containing anatase TiO2. The PANI-TiO2
      nanocomposite consisted of short-chained fibrous structure of PANI with spherical
      TiO2 nanoparticles dispersed at the tips and edge of the fibres. The average
      hydrodynamic diameter of the nanocomposite was 99.5 nm. The band gap energy was
      2.1 eV which showed its ability to absorb light in the visible range. The
      nanocomposite exhibited better visible light-mediated photocatalytic activity
      than TiO2 (Degussa P25) in terms of degradation of Reactive Blue (RB-19) dye. The
      photocatalysis was favoured under initial acidic pH, and complete degradation of
      50 mg/L dye could be achieved at optimum catalyst loading of 1 g/L. The kinetics
      of degradation followed the Langmuir-Hinshelhood model. PANI-TiO2 nanocomposite
      showed almost similar photocatalytic activity under UV and visible light as well
      as in the solar light which comprises of radiation in both UV and visible light
      range. Chemical oxygen demand removal of 86% could also be achieved under visible
      light, confirming that simultaneous mineralization of the dye occurred during
      photocatalysis. PANI-TiO2 nanocomposites are promising photocatalysts for the
      treatment of industrial wastewater containing RB-19 dye.

PMID- 29168136
TI  - Adsorption of cadmium ions using the bioadsorbent of Pichia kudriavzevii YB5
      immobilized by polyurethane foam and alginate gels.
AB  - Pichia kudriavzevii YB5, mutated from Pichia kudriavzevii A16 with a strong
      ability to remove cadmium ions, was immobilized by polyurethane foam and alginate
      gels in this work. The immobilization conditions were optimized as follows:
      sodium alginate concentration of 2% (w/v), calcium chloride concentration of 2%
      (w/v), biomass dose of 1 * 109 cell/mL, and cross-linking time for 4 h. Then, the
      results of batch adsorption experiments showed that the removal capacity of
      prepared bioadsorbent was significantly affected by the pH of media, contact
      time, and the initial Cd(II) concentration, and a suitable adsorption conditions
      of Cd(II) could be achieved with a pH value of 6.0 at 20  degrees C for 90 min.
      Kinetic and isothermal results indicated the behavior of Cd(II) adsorption onto
      immobilized P. kudriavzevii YB5 fitted to the pseudo-second-order kinetic
      equation and the Langmuir adsorption model. Thermodynamic results showed that the
      Cd(II) adsorption process was endothermic and spontaneous in nature. Besides, the
      Cd(II) removing capacity of the prepared bioadsorbent was also tested in the
      oyster hydrolysates, showing an average removal rate of 54.35%. Thus, the
      immobilized P. kudriavzevii YB5 adsorbent had great potential for application in
      aquatic products to ensure the food safety.

PMID- 29168137
TI  - Pesticide residues in muscles of some marine fish species and seaweeds of
      Iskenderun Bay (Northeastern Mediterranean), Turkey.
AB  - Pesticide residues in muscles of nine marine fish and four seaweed species of
      Iskenderun Bay (Northeastern Mediterranean) have been investigated. In sampled
      fish species, two herbicides, three insecticides, two fungicides, and one
      synergist were identified and quantified. Metribuzin DADK, propamocarb HCl, and
      piperonyl butoxide (PBO) were detected in all the muscles of sampled fish
      species. Metribuzin DADK was the most abundant pesticide residue in fish muscles
      and the highest metribuzin DADK concentration was found in sardine (311.20
      MUg/kg). Propamocarb HCl concentrations varied greatly among species; from 0.530
      +/- 0.020 MUg/kg in striped sea bream to 34.170 MUg/kg in sea bass. The level of
      PBO ranged from 0.001 MUg/kg for fourlined terapon to 0.013 MUg/kg for sardine.
      No measurable oxamyl residue was found in any of the muscles of sampled fish
      species (except sardine). In seaweeds, two herbicides and two insecticides were
      identified and quantified. Metribuzin DADK was the most abundant and found in
      Cystoseira corniculata (5.01 mg/kg), Corallina elongata (0.703 mg/kg), and Jania
      rubens (3.85 mg/kg). Molinate was a minor contaminant and only found in Corallina
      elongata (0.002 mg/kg). Pyrethrin I was determined only in Padina pavonia to be
      0.567 mg/kg. Pyrethrine II was found in Padina pavonia and Corallina elongate to
      be 1.214 and 0.229 mg/kg, respectively. The most hazardous pesticide residues of
      organochlorines and organophosphorus were not detected in both sampled fish
      muscles and seaweeds. There are no clear maximum residue limits for the detected
      eight pesticide residues declared for fish muscle by European Union MRL (2017).
      In conclusion, it can be considered that observed concentrations of pesticides in
      sampled nine marine fish species do not have a potential health risk for
      consumers. Some of the detected pesticide residues can be toxic for algae and
      aquatic life and regular monitoring studies are therefore essential to control
      the pesticide concentrations of aquatic biota in the region.

PMID- 29168138
TI  - Metabolomic analysis of the toxic effect of chronic exposure of cadmium on rat
      urine.
AB  - This study aimed to assess the toxic effect of chronic exposure to cadmium
      through a metabolomic approach based on ultra-performance liquid
      chromatography/mass spectrometry (UPLC-MS). Forty male Sprague-Dawley rats were
      randomly assigned to the following groups: control, low-dose cadmium chloride
      (CdCl2) (0.13 mg/kg body weight (bw)), middle-dose CdCl2 (0.8/kg bw), and high
      dose CdCl2 (4.9 mg/kg bw). The rats continuously received CdCl2 via drinking
      water for 24 weeks. Rat urine samples were then collected at different time
      points to establish the metabolomic profiles. Multiple statistical analyses with
      principal component analysis and partial least squares-discriminant analysis were
      used to investigate the metabolomic profile changes in the urine samples and
      screen for potential biomarkers. Thirteen metabolites were identified from the
      metabolomic profiles of rat urine after treatment. Compared with the control
      group, the treated groups showed significantly increased intensities of
      phenylacetylglycine, guanidinosuccinic acid, 4-pyridoxic acid, 4-aminohippuric
      acid, 4-guanidinobutanoic acid, allantoic acid, dopamine, LysoPC(18:2(9Z,12Z)),
      and L-urobilinogen. By contrast, the intensities of creatinine, L-carnitine,
      taurine, and pantothenic acid in the treated groups were significantly decreased.
      These results indicated that Cd disrupts energy and lipid metabolism. Meanwhile,
      Cd causes liver and kidney damage via induction of oxidative stress; serum
      biochemical indices (e.g., creatinine and urea nitrogen) also support the
      aforementioned results.

PMID- 29168139
TI  - Applicability of energy-positive net-zero water management in Alaska: technology
      status and case study.
AB  - Challenges of water and wastewater management in Alaska include the potential
      need for above-grade and freeze-protected piping, high unit energy costs and, in
      many rural areas, low population density and median annual income. However,
      recently developed net-zero water (NZW), i.e., nearly closed-loop, direct potable
      water reuse systems, can retain the thermal energy in municipal wastewater,
      producing warm treated potable water without the need for substantial water re
      heating, heat pumping or transfer, or additional energy conversion. Consequently,
      these systems are projected to be capable of saving more energy than they use in
      water treatment and conveyance, in the temperate USA. In this paper, NZW
      technology is reviewed in terms of potential applicability in Alaska by
      performing a hypothetical case study for the city of Fairbanks, Alaska. Results
      of this paper study indicate that in municipalities of Alaska with local
      engineering and road access, the use of NZW systems may provide an energy
      efficient water service option. In particular, case study modeling suggests hot
      water energy savings are equivalent to five times the energy used for treatment,
      much greater savings than in mid-latitudes, due largely to the substantially
      higher energy needed for heating water from a conventional treatment system and
      lack of need for freeze-protected piping. Further study of the applicability of
      NZW technology in cold regions, with expanded evaluation in terms of system-wide
      lifecycle cost, is recommended.

PMID- 29168140
TI  - Three-dimensional magnetic resonance visualisation of fistula-in-ano.

PMID- 29168141
TI  - Initial experience with taTME in patients undergoing laparoscopic restorative
      proctocolectomy for familial adenomatous polyposis.
AB  - BACKGROUND: Transanal total mesorectal excision (taTME) is a minimally invasive
      technique which was developed to overcome the difficulties associated with the
      "top-down" pelvic dissection by enabling a "bottom-up" dissection in patients
      with mid- and low rectal cancer. While this technique was primarily designed to
      manage tumors in the mid- and lower rectum, its spectrum of indications has been
      broadened to include benign colorectal pathologies. The aim of the present study
      was to assess our initial experience with taTME in patients undergoing
      restorative proctocolectomy for familial adenomatous polyposis (FAP). METHODS:
      All consecutive patients (undergoing prophylactic restorative proctocolectomy
      with IPAA for FAP using taTME between April and October 2016 at our institution)
      were included in the study. RESULTS: There were 8 patients (6 females and 2
      males). The median age was 19.5 years (range 16-31 years). In all cases, surgery
      was successfully completed using with taTME. No perioperative complications were
      recorded. A median of 5 bowel movements (range 4-6 bowel movements) with
      intermittent anti-diarrheal medication was recorded in all cases. CONCLUSIONS:
      Our initial experience with 8 consecutive cases suggests taTME is safe and
      effective in patients undergoing prophylactic restorative proctocolectomy with
      IPAA for FAP.

PMID- 29168142
TI  - Incidental IVC tumor thrombus found on echocardiographic work-up for systolic
      murmur leading to new diagnosis of renal cell carcinoma.

PMID- 29168143
TI  - Very late drug-eluting stent thrombosis in superficial femoral artery involving
      common femoral artery.

PMID- 29168145
TI  - Erratum to: Purification of Cyclic GMP-AMP from Viruses and Measurement of Its
      Activity in Cell Culture.

PMID- 29168144
TI  - A Review of Chronic Granulomatous Disease.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by
      defects in any of the five subunits of the NADPH oxidase complex responsible for
      the respiratory burst in phagocytic leukocytes. Patients with CGD are at
      increased risk of life-threatening infections with catalase-positive bacteria and
      fungi and inflammatory complications such as CGD colitis. The implementation of
      routine antimicrobial prophylaxis and the advent of azole antifungals has
      considerably improved overall survival. Nevertheless, life expectancy remains
      decreased compared to the general population. Inflammatory complications are a
      significant contributor to morbidity in CGD, and they are often refractory to
      standard therapies. At present, hematopoietic stem cell transplantation (HCT) is
      the only curative treatment, and transplantation outcomes have improved over the
      last few decades with overall survival rates now > 90% in children less than 14
      years of age. However, there remains debate as to the optimal conditioning
      regimen, and there is question as to how to manage adolescent and adult patients.
      The current evidence suggests that myeloablative conditioning results is more
      durable myeloid engraftment but with increased toxicity and high rates of graft
      versus-host disease. In recent years, gene therapy has been proposed as an
      alternative to HCT for patients without an HLA-matched donor. However, results to
      date have not been encouraging. with negligible long-term engraftment of gene
      corrected hematopoietic stem cells and reports of myelodysplastic syndrome due to
      insertional mutagenesis. Multicenter trials are currently underway in the United
      States and Europe using a SIN-lentiviral vector under the control of a myeloid
      specific promoter, and, should the trials be successful, gene therapy may be a
      viable option for patients with CGD in the future.

PMID- 29168146
TI  - Novel Direct Annuloplasty Fastener System for Minimally Invasive Mitral Valve
      Repair.
AB  - The development of less invasive approaches for mitral valve repair remains an
      important objective, particularly in patients with multiple comorbidities. We
      describe a novel method to affix a mitral valve annuloplasty ring in a minimally
      invasive manner. A delivery apparatus for an annuloplasty fastener system was
      designed. Two channels were created, one for advancing the annuloplasty ring, and
      another to accommodate the fastener applicator. Custom designed fasteners, either
      with a helical-shaped screw or a strap-shaped tack structure, were tested.
      Fasteners were primed within an application device and automatic alignment of
      fasteners was achieved to allow accurate firing of the fixators securing the
      ring. The delivery apparatus was constructed to be deployed within a 10 mm trocar
      through a left atrial approach. Using a cadaveric swine heart model, access to
      the mitral valve from the left atrium was obtained with insertion of a trocar.
      The delivery apparatus was accurately directed to the mitral annulus under
      echocardiographic guidance. Fasteners were placed along the annular plane to
      secure the annuloplasty ring. Both fastener designs achieved considerable
      fixation force; the helical-shaped screw was found to have significantly greater
      fixation force compared to the strap-shaped tack design. The annuloplasty ring
      remained intact and did not experience any structural deformity during the
      fixation process. The use of a novel fastener system was successful in deploying
      and securing a mitral valve annuloplasty ring. These promising results may have
      further application for minimally invasive mitral valve repairs. Additional
      evaluation of this procedure with pre-clinical in vivo animal studies is
      necessary.

PMID- 29168147
TI  - Generation and characterization of tissue-type plasminogen activator transgenic
      rats.
AB  - To address a species difference in the responsiveness to human recombinant tissue
      type plasminogen activator (rt-PA) between rats and humans, tPA transgenic (Tg)
      rats were generated and characterized. In the rats, transcriptional regulation of
      tPA was designed under the control of the endogenous tPA promoter. There were no
      significant differences in hematological parameters between the tPA Tg and non Tg
      rats. Plasma tPA concentration was significantly increased and serum free PAI-1
      was significantly decreased in the tPA Tg rats. Significant overexpression of tPA
      mRNA in five major organs was also confirmed in the tPA Tg rats. In contrast, the
      extent of tPA mRNA induction by pathophysiological stimuli (focal cerebral
      ischemia) was comparable in the two strains. Earlier increase in the plasma D
      Dimer level was observed in the tPA Tg rats in a model of thromboembolism
      compared with the non Tg rats. On the other hand, there was no statistically
      significant prolongation of bleeding time in a rat model of bleeding between the
      two strains. rt-PA showed dose-related blood flow restoration in a rat model of
      thromboembolic stroke in the tPA Tg rats from a dose (1 mg/kg, i.v.) similar to
      clinical doses for human stroke patients. In conclusion, tPA Tg rats, in which
      tPA is overexpressed and endogenous fibrinolytic activity is enhanced without
      hemostatic abnormality, were generated. tPA Tg rats would be beneficial for the
      pharmacological and the toxicological evaluation of rt-PA and other various
      fibrinolytic enhancers.

PMID- 29168149
TI  - Revision of Podocotyloides Yamaguti, 1934 (Digenea: Opecoelidae), resurrection of
      Pedunculacetabulum Yamaguti, 1934 and the naming of a cryptic opecoelid species.
AB  - Despite morphological and ecological inconsistencies among species, all
      plagioporine opecoelids with a pedunculate ventral sucker are currently
      considered to belong in the genus Podocotyloides Yamaguti, 1934. We revise the
      genus based on combined morphological and phylogenetic analyses of novel material
      collected from haemulid fishes in Queensland waters that we interpret to
      represent species congeneric with the type-species, Pod. petalophallus Yamaguti,
      1934, also known from a haemulid, off Japan. Our phylogenetic analysis
      demonstrates polyphyly of Podocotyloides; prompts us to resurrect
      Pedunculacetabulum Yamaguti, 1934; and suggests that Pod. brevis Andres &
      Overstreet, 2013, from a deep-sea congrid in the Caribbean, and Pod. parupenei
      (Manter, 1963) Pritchard, 1966 and Pod. stenometra Pritchard, 1966, from mullids
      and chaetodontids, respectively, on the Great Barrier Reef, may each represent a
      distinct genus awaiting recognition. Our revised concept of Podocotyloides
      requires a pedunculate ventral sucker, but also a uterine sphincter prior to the
      genital atrium, a petalloid cirrus appendage, restriction of the vitelline
      follicles to the hindbody, and for the excretory vesicle to reach to the level of
      the ventral sucker. Of about 20 nominal species, we recognise just three in
      Podocotyloides (sensu stricto): Pod. petalophallus, Pod. gracilis (Yamaguti,
      1952) Pritchard, 1966 and Pod. magnatestes Aleshkina & Gaevskaya, 1985. We
      provide new records for Pod. gracilis, and propose two new species of
      Podocotyloides, Pod. australis n. sp. and Pod. brevivesiculatus n. sp., and one
      new Pedunculacetabulum species, Ped. inopinipugnus n. sp., all from haemulids.
      Podocotyloides australis is morphologically indistinguishable from Pod. gracilis,
      and exploits the same definitive host, but is genetically and biogeographically
      distinct. It is thus a cryptic species, the first such opecoelid to be formally
      named.

PMID- 29168148
TI  - Developing a bacteriophage cocktail for biocontrol of potato bacterial wilt.
AB  - Bacterial wilt is a devastating disease of potato and can cause an 80% production
      loss. To control wilt using bacteriophage therapy, we isolated and characterized
      twelve lytic bacteriophages from different water sources in Kenya and China.
      Based on the lytic curves of the phages with the pathogen Ralstonia solanacearum,
      one optimal bacteriophage cocktail, P1, containing six phage isolations was
      formulated and used for studying wilt prevention and treatment efficiency in
      potato plants growing in pots. The preliminary tests showed that the phage
      cocktail was very effective in preventing potato bacterial wilt by injection of
      the phages into the plants or decontamination of sterilized soil spiked with R.
      solanacearum. Eighty percent of potato plants could be protected from the
      bacterial wilt (caused by R. solanacearum reference strain GIM1.74 and field
      isolates), and the P1 cocktail could kill 98% of live bacteria spiked in the
      sterilized soil at one week after spraying. However, the treatment efficiencies
      of P1 depended on the timing of application of the phages, the susceptibility of
      the plants to the bacterial wilt, as well as the virulence of the bacteria
      infected, suggesting that it is important to apply the phage therapy as soon as
      possible once there are early signs of the bacterial wilt. These results provide
      the basis for the development of bacteriophagebased biocontrol of potato
      bacterial wilt as an alternative to the use of antibiotics.

PMID- 29168150
TI  - Phylogenetic relationships of the genus Armadolepis Spassky, 1954 (Eucestoda,
      Hymenolepididae), with descriptions of two new species from Palaearctic dormice
      (Rodentia, Gliridae).
AB  - Two new species of hymenolepidid cestodes belonging to the genus Armadolepis
      Spassky, 1954 are described from dormice (Gliridae) from the southern East
      European Plain and the northwestern Caucasus, Russia. Armadolepis (Bremserilepis)
      longisoma n. sp., with a rudimentary, unarmed rostellar apparatus is described
      from the fat dormouse Glis glis (Linnaeus) from the Republic of Adygeya, Russia.
      Additionally, A. (Armadolepis) dryomi n. sp., characterised by a well-developed
      rostellar apparatus and armed rhynchus is described from the forest dormouse
      Dryomys nitedula Pallas from Rostov Oblast', Russia. Armadolepis (Bremserilepis)
      longisoma n. sp. differs from A. (Bremserilepis) myoxi (Rudolphi, 1819) in having
      a substantially longer strobila and cirrus-sac, wider scolex and ovary and larger
      rostellar pouch and testes. Armadolepis (Armadolepis) dryomi n. sp. is
      distinguishable from A. (Armadolepis) spasskii Tenora & Barus, 1958, A.
      (Armadolepis) jeanbaeri Makarikov, 2017 and A. (Armadolepis) tenorai Makarikov,
      2017 in having a substantially longer and wider strobila, and larger rostellar
      pouch and cirrus-sac. Furthermore, A. dryomi n. sp. can be distinguished from its
      congeners by the number and size of rostellar hooks and the arrangement of the
      testes. Phylogenetic affinities of Armadolepis were studied for the first time
      using partial sequences of the nuclear ribosomal 28S DNA gene. Phylogenetic
      analysis strongly supported the status of Armadolepis as a separate genus
      belonging to the "Rodentolepis clade".

PMID- 29168151
TI  - Capillaria appendigera n. sp. (Nematoda: Capillariidae) from the goldbanded
      jobfish Pristipomoides multidens (Day) (Lutjanidae) and new records of other
      intestinal capillariids from marine perciform fishes off Australia.
AB  - Based on light and scanning electron microscopical studies, a new nematode
      parasite, Capillaria appendigera n. sp. (Capillariidae), is described from the
      intestine of the goldbanded jobfish Pristipomoides multidens (Day) (Perciformes,
      Lutjanidae) from the Arafura Sea West, off the northern coast of Australia. The
      new species, belonging to the subgenus Procapillaria Moravec, 1987, differs from
      other congeneric species from fishes mainly in the length (0.92-1.13 mm), shape
      and structure of the spicule, obtuse spines on the spicule sheath and the
      structure of eggs. It is characterised, in the male, by the presence of two well
      developed dorsolateral caudal lobes, a pair of lateral papillae, a heavily
      sclerotised spicule with many rough transverse grooves covering almost the entice
      spicule surface (except for spicule ends), a spinose spicule sheath, and in the
      female, by a subterminal anus, mostly the presence of a large vulval appendage
      and by eggs (size 54-69 * 27-33 um) encapsulated by a conspicuous light-coloured
      superficial layer. Capillaria appendigera n. sp. is the 12th nominal species of
      capillariids recorded from fishes in Australian waters and the second known
      capillariid species parasitising fishes of the perciform family Lutjanidae. In
      addition, four unidentifiable, morphologically different types of capillariid
      females, probably representing undescribed species, were recorded from the
      intestines of marine fishes off the northern coast of Australia: Capillariidae
      gen. sp. 1 and Capillariidae gen. sp. 2 from Lutjanus johnii (Bloch) and L.
      malabaricus (Bloch & Schneider), respectively (both Lutjanidae), Capillariidae
      gen. sp. 3 from Protonibea diacanthus (Lacepede) (Sciaenidae) and Capillariidae
      gen. sp. 4 from Rachycentron canadum (Linnaeus) (Rachycentridae).

PMID- 29168152
TI  - Dermatomyositis and colorectal cancer: a systematic review.
AB  - BACKGROUND: Dermatomyositis (DM) is an idiopathic inflammatory myositis. The
      principal characteristics are cutaneous rash, muscle ache, and muscle weakness.
      In the past, associations have been established between DM and malignancy,
      including colorectal cancer. METHODS: A systematic PubMed and Scopus search was
      conducted. RESULTS: The median age of the patients was 65 years (range 40-82).
      The majority were female (17 out of 27, 63%). Adenocarcinoma was the most
      frequent histological type of colorectal neoplasm. DM manifested before the
      diagnosis of colorectal cancer in 21 out of 27 patients (77.8%). At the time of
      the first presentation, creatine kinase was at a median level of 514.5 U/L (range
      50-11,744), and serum antibodies were present in 11 out of 27 patients (40.7%).
      Immediate improvement of DM symptoms after surgery occurred in 14 out of 26
      patients (53.8%). Recurrence of cancer in the form of distal metastasis was
      present in 5 out of 26 patients (19.2%). Cancer recurrence occurred within a
      median of 7.9 months (range 2-21) after surgery. In 7 out of 26 patients (26.9%),
      DM symptoms recurred during the post-operative period. Death was reported in 23
      out of 27 patients (85.2%). CONCLUSION: It is of paramount importance to perform
      a systematic diagnostic workup for malignancy, always including colonoscopy, in
      DM patients, since there is a high incidence of cancer in DM patients. Surgical
      treatment of colorectal tumors should precede the treatment of DM, as DM will
      frequently regress after a successful resection of malignancy.

PMID- 29168154
TI  - The Effect of Probiotics on Halitosis: a Systematic Review and Meta-analysis.
AB  - Although several studies have evaluated the inhibitory effect of probiotics on
      halitosis, findings are inconsistent. This systematic review and meta-analysis of
      randomized clinical trials (RCT) was conducted to summarize the evidence on the
      effect of probiotics on halitosis. RCT on any type of probiotic treatment with at
      least 2-week duration were identified through electronic databases (PubMed,
      EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials)
      and hand searched between 1946 and January 17, 2017. Primary outcomes were
      organoleptic (OLT) scores and volatile sulfur compounds (VSC). Standardized mean
      difference (SMD) and 95% confidence interval (CI) were calculated. Meta-analysis
      was conducted to synthesize the evidence. Of the 153 articles identified, three
      met the inclusion criteria. Meta-analysis revealed that OLT scores (SMD = - 1.93,
      95% CI - 2.85 to - 1.02, P < 0.0001) were significantly lower in subjects who
      received probiotics than in placebo groups, but no significant difference was
      observed at the VSC concentration (SMD = - 0.02, 95% CI - 2.12 to 2.07, P =
      0.98). Current evidence is supportive of recommending probiotics for the
      management of halitosis. Based on this review, transient (average of 2 weeks)
      dosing with probiotics (mainly Lactobacillus strains) has a moderate effect on
      halitosis regarding OLT scores, but we could not confirm the effects of
      probiotics on the VSC reduction. The available evidence is quantitatively and
      qualitatively insufficient for further recommendations, especially with regard to
      administration strategies and pretreatment. Future studies should aim for longer
      follow-up and standardized administration methods to prove or refute the effect
      of probiotics on halitosis.

PMID- 29168153
TI  - Redesigning of Microbial Cell Surface and Its Application to Whole-Cell
      Biocatalysis and Biosensors.
AB  - Microbial cell surface display technology can redesign cell surfaces with
      functional proteins and peptides to endow cells some unique features. Foreign
      peptides or proteins are transported out of cells and immobilized on cell surface
      by fusing with anchoring proteins, which is an effective solution to avoid
      substance transfer limitation, enzyme purification, and enzyme instability. As
      the most frequently used prokaryotic and eukaryotic protein surface display
      system, bacterial and yeast surface display systems have been widely applied in
      vaccine, biocatalysis, biosensor, bioadsorption, and polypeptide library
      screening. In this review of bacterial and yeast surface display systems,
      different cell surface display mechanisms and their applications in biocatalysis
      as well as biosensors are described with their strengths and shortcomings. In
      addition to single enzyme display systems, multi-enzyme co-display systems are
      presented here. Finally, future developments based on our and other previous
      reports are discussed.

PMID- 29168155
TI  - In Silico and Experimental Data Claiming Safety Aspects and Beneficial Attributes
      of the Bacteriocinogenic Strain Enterococcus faecalis B3A-B3B.
AB  - This study aimed at comparing the genome of Enterococcus faecalis B3A-B3B, a
      bacteriocinogenic strain recently isolated from a healthy Iraqi infant to those
      of Enterococci of clinical and beneficial grades. The putative genes gelE, cpd,
      efaAfm, ccf, agg, and cob coding for virulence factors were detected in B3A-B3B
      strain, which meanwhile resulted to be non-cytotoxic, non-hemolytic, devoid of
      inflammatory effects, and sensitive to most of the antibiotics tested except for
      clindamycin and trimethoprim, which resistance is usually ascribed to intrinsic
      nature. B3A-B3B strain was remarkable for its hydrophobicity, auto-aggregation,
      adhesion to human Caco-2 cells, and survival in simulated gastrointestinal
      conditions, and cholesterol assimilation fulfilling therefore key beneficial
      attributes.

PMID- 29168156
TI  - The anesthetic management of button battery ingestion in children.
AB  - PURPOSE: Injuries related to button battery ingestion are common in children.
      This review provides an outline of the epidemiology, pathophysiology, management,
      and anesthetic implications in children who have ingested a button battery.
      SOURCE: A literature search was conducted in the United States National Library
      of Medicine PubMed database using the terms "button battery ingestion" and
      "children' and "removal" and "surgery" and "anesthesia". Ninety-six articles
      published in English were found from 1983-2017, and 62 of these articles were
      incorporated into this review. Additionally, the Internet was searched with the
      terms "button battery ingestion and children" to identify further entities,
      organizations, and resources affiliated with button battery ingestion in
      children. These additional sources were studied and included in this review.
      PRINCIPAL FINDINGS: Button batteries are ubiquitous in homes and electronic
      devices. Since 2006, larger-diameter and higher-voltage batteries have become
      available. These are more likely to become impacted in the esophagus after
      ingestion and lead to an increase in severe morbidity and mortality due to
      caustic tissue injury. Children at the highest risk for complications are those
      under six years of age who have ingested batteries > 20 mm in diameter and
      sustain prolonged esophageal impaction at the level of the aortic arch with the
      negative pole oriented anteriorly. CONCLUSION: Anesthesiologists need to know
      about the epidemiology, pathophysiology, complications, and anesthetic management
      of children who have ingested button batteries.

PMID- 29168157
TI  - Perioperative implications of sodium-glucose cotransporter-2 inhibitors: a case
      series of euglycemic diabetic ketoacidosis in three patients after cardiac
      surgery.
AB  - PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) comprise the newest
      class of oral hypoglycemic agents approved for treating type II diabetes mellitus
      (DM-II). Their use, however, has been associated with the rare development of
      euglycemic diabetic ketoacidosis (euDKA). We present three cases of euDKA that
      occurred following elective coronary artery bypass grafting surgery. The role of
      the anesthesiologist in the prevention, diagnosis, and management of this
      complication is also discussed. CLINICAL FEATURES: Three patients receiving
      chronic SGLT2i therapy for DM-II (discontinued one to two days preoperatively)
      underwent cardiac surgery. On the first postoperative day, each exhibited nausea,
      vomiting, and tachypnea. Although these nonspecific postoperative findings are
      common, our patients also exhibited anion gap metabolic acidosis (pH < 7.3, anion
      gap > 12 mmol.L-1) with lower than anticipated serum glucose levels of < 14
      mmol.L-1. Serum and urine ketone analyses confirmed a diagnosis of euDKA. After
      insulin and dextrose infusions were initiated, rapid resolution of the metabolic
      abnormalities occured. CONCLUSIONS: Anesthesiologists should recognize that
      patients receiving SGLT2i preoperatively are at risk of developing euDKA. Hence,
      based on the pharmacokinetics of SGLT2i, discontinuing the medication at least
      two days prior to surgery should minimize the risk. Diagnosing euDKA is
      challenging and often delayed because of its nonspecific signs and symptoms. When
      suspected, serum and urine ketones should be monitored to reduce the time to
      diagnosis and treatment.

PMID- 29168158
TI  - Assessment of attenuation correction for myocardial PET imaging using combined
      PET/MRI.
AB  - OBJECTIVE: To evaluate the frequency of artifacts in MR-based attenuation
      correction (AC) maps and their impact on the quantitative accuracy of PET-based
      flow and metabolism measurements in a cohort of consecutive heart failure
      patients undergoing combined PET/MR imaging. METHODS: Myocardial viability
      studies were performed in 20 patients following a dual-tracer protocol involving
      the assessment of myocardial perfusion (13N-NH3: 813 +/- 86 MBq) and metabolism
      (18F-FDG: 335 +/- 38 MBq). All acquisitions were performed using a fully
      integrated PET/MR system, with standard DIXON-attenuation correction (DIXON-AC)
      mapping for each PET scan. All AC maps were examined for spatial misalignment
      with the emission data, total lung volume, susceptibility artifacts, and tissue
      inversion (TI). Misalignment and susceptibility artifacts were corrected using
      rigid co-registration and retrospective filling of the susceptibility-induced
      gaps, respectively. The effects of the AC artifacts were evaluated by relative
      difference measures and perceived changes in clinical interpretations. RESULTS:
      Average respiratory misalignment of (7 +/- 4) mm of the PET-emission data and the
      AC maps was observed in 18 (90%) patients. Substantial changes in the lung
      volumes of the AC maps were observed in the test-retest analysis (ratio: 1.0 +/-
      0.2, range: 0.8-1.4). Susceptibility artifacts were observed in 10 (50%)
      patients, while six (30%) patients had TI artifacts. Average differences of 14 +/
      10% were observed for PET images reconstructed with the artifactual AC maps. The
      combined artifact effects caused false-positive findings in three (15%) patients.
      CONCLUSION: Standard DIXON-AC maps must be examined carefully for artifacts and
      misalignment effects prior to AC correction of cardiac PET/MRI studies in order
      to avoid misinterpretation of biased perfusion and metabolism readings from the
      PET data.

PMID- 29168159
TI  - LOX-1 is a poor prognostic indicator and induces epithelial-mesenchymal
      transition and metastasis in pancreatic cancer patients.
AB  - PURPOSE: Pancreatic cancer (PC) is an aggressive type of cancer that exhibits a
      rapid progression. Previously LOX-1, which is a type II trans-membrane
      glycoprotein that is expressed in endothelial cells, has been found to be
      involved in the development of several types of cancer. As yet, however, the
      expression of LOX-1 and its functional consequences in PC have not been
      documented. The present study was aimed at investigating the prognostic relevance
      of LOX-1 expression in PC patients and at resolving its role in PC metastasis.
      METHODS: LOX-1 expression was assessed by immunohistochemistry on a tissue
      microarray containing samples from 98 PC patients. Kaplan-Meier analyses were
      performed to compare survival curves, whereas Cox regression analyses were
      performed to explore the independent prognostic value of LOX-1 expression on the
      overall survival (OS) of PC patients. Harrel's concordance index was applied to
      calculate the predictive accuracy of established models. In addition, in vitro
      scratch wound healing and Transwell assays were used to assess the effect of LOX
      1 expression silencing and over-expression on PC cell migration and invasion,
      whereas Cell Counting Kit-8 (CCK8) and Flow Cytometry (FCM) assays were used to
      assess its effects on PC cell proliferation and apoptosis. RESULTS: We found that
      LOX-1 is highly expressed in the PC tumor tissues tested and is related to the
      occurrence of lymph node metastases, higher TNM stages and a poor OS. We also
      found that LOX-1 expression may serve as an independent prognostic factor for the
      OS of PC patients. Our in vitro assays revealed that LOX-1 expression may promote
      the migration and invasion of PC cells through epithelial-mesenchymal transition
      (EMT). No effect on PC cell proliferation was noted. CONCLUSIONS: From our data
      we conclude that a high LOX-1 expression in PC tissues is indicative for the
      occurrence of lymph node metastases, high TNM stages and a poor prognosis. LOX-1
      may serve as an independent prognostic biomarker. Our in vitro assays
      additionally revealed that LOX-1 may enhance the migration and invasion of PC
      cells through EMT. LOX-1 may also serve as a novel therapeutic target.

PMID- 29168160
TI  - Cladribine to Treat Relapsing Forms of Multiple Sclerosis.
AB  - Cladribine is a purine nucleoside analogue that selectively depletes peripheral
      lymphocytes without a major impact on cells of the innate immune system. An oral
      formulation of cladribine has been developed to be given as short courses over
      two annual cycles. Oral cladribine results in the peripheral depletion of
      lymphocytes that is gradual, occurring over several weeks, and is not associated
      with a cell lysis syndrome, has a greater impact on B cells than T cells, and is
      followed by gradual reconstitution of the peripheral lymphocyte counts over
      several months. Oral cladribine is effective in relapsing forms of multiple
      sclerosis. As a selective immune reconstitution therapy (SIRT), cladribine acts
      as a short-term immunosuppressant, relative to other maintenance
      immunosuppressive therapies that result in long-term immunosuppression. The main
      safety signal that has emerge relates primarily to herpes zoster infection, which
      was more common in patients with higher grades of lymphopenia, in particular
      grade 3 and 4 lymphopenia. Data from the oral cladribine extension trial and
      safety register, and reanalysis of the pivotal phase III trial has indicated that
      oral cladribine is unlikely to be associated with an increased short- to
      intermediate-term risk of malignancy.

PMID- 29168161
TI  - A Multilevel Approach to Breastfeeding Promotion: Using Healthy Start to Deliver
      Individual Support and Drive Collective Impact.
AB  - Purpose Breastfeeding has been linked to a host of positive health effects for
      women and children. However, disparities in breastfeeding initiation and duration
      prevent many low-income and African-American women from realizing these benefits.
      Existing breastfeeding promotion efforts often do not reach women who need
      support the most. In response, the Westside Healthy Start program (WHS), located
      in Chicago, Illinois, developed an ongoing multilevel approach to breastfeeding
      promotion. Description Key elements of our WHS breastfeeding model include
      individual education and counseling from pregnancy to 6 months postpartum and
      partnership with a local safety-net hospital to implement the Baby-Friendly
      Hospital Initiative and provide lactation support to delivering patients.
      Assessment In the year our model was implemented, 44.6% (49/110) of prenatal WHS
      participants reported that they planned to breastfeed, and 67.0% (183/273) of
      delivered participants initiated. Among participants reaching 6 months
      postpartum, 10.5% (9/86) were breastfeeding. WHS also had 2667 encounters with
      women delivering at our partner hospital during breastfeeding rounds, with 65.1%
      of contacts initiating. Community data was not available to assess the efficacy
      of our model at the local level. However, WHS participants fared better than all
      delivering patients at our partner hospital, where 65.0% initiated in 2015.
      Conclusion Healthy Start programs are a promising vehicle to improve
      breastfeeding initiation at the individual and community level. Additional
      evaluation is necessary to understand barriers to duration and services needed
      for this population.

PMID- 29168162
TI  - House Parties: An Innovative Model for Outreach and Community-Based Health
      Education.
AB  - Purpose To connect low resource communities to innovative services that address
      gaps in health access and knowledge. Description We describe the house party
      model, as a community-based workshop approach to health education developed by
      the Westside Healthy Start program (WHS) in Chicago, Illinois. Key elements of
      the WHS house party model include use of community health workers as
      facilitators, collaboration with participants and community-based organizations,
      referrals to health care and social services, and engagement strategies such as
      interactive activities, personal stories, and discussion. Assessment In 2014 and
      2015, WHS completed 23 house parties with 271 participants, delivering education
      on relevant maternal and child health (MCH) topics. Participants demonstrated
      improvements in knowledge of several health-related areas. About half of
      participants were able to identify causes or signs of preterm labor prior to the
      house party, compared to over 80% after. In addition, 94% of participants rated
      the house party workshops "excellent" or "good". Conclusion House parties are a
      promising strategy for increasing knowledge about MCH topics and linking hard-to
      reach populations to resources in the community.

PMID- 29168163
TI  - A Pilot Quality Improvement Collaborative to Improve Safety Net Dental Access for
      Pregnant Women and Young Children.
AB  - Objectives To determine acceptability and feasibility of a quality improvement
      (QI) collaborative in safety net dental practices, and evaluate its effects on
      financial stability, access, efficiency, and care for pregnant women and young
      children. Methods Five safety net dental practices participated in a 15-month
      learning collaborative utilizing business assessments, QI training, early
      childhood oral health training, and prenatal oral health training. Practices
      collected monthly data on: net revenue, no-show rates, total encounters, and
      number of encounters for young children and pregnant women. We analyzed
      quantitative data using paired t-tests before and after the collaborative and
      collected supplemental qualitative feedback from clinic staff through focus
      groups and directed email. Results All mean measures improved, including: higher
      monthly revenue ($28,380-$33,102, p = 0.37), decreased no-show rate (17.7-14.3%,
      p = 0.11), higher monthly dental health encounters (283-328, p = 0.08), and
      higher monthly encounters for young children (8.8-10.5, p = 0.65), and pregnant
      women (2.8-9.7, p = 0.29). Results varied by practice, with some demonstrating
      largest increases in encounters for young children and others pregnant women.
      Focus group participants reported that the collaborative improved access for
      pregnant women and young children, and that QI methods were often new and
      difficult. Conclusion for practice Participation by safety net dental practices
      in a QI collaborative is feasible and acceptable. Individual sites saw greater
      improvements in different outcomes areas, based on their own structures and
      needs. Future efforts should focus on specific needs of each dental practice and
      should offer additional QI training.

PMID- 29168164
TI  - Meeting patient expectations: patient expectations and recovery after hip or knee
      surgery.
AB  - BACKGROUND: Although patient-centred care could help increase the value of
      healthcare, practice variations in hip and knee surgery suggest that physicians
      guide clinical decisions more than patients do. This raises the question whether
      treatment outcomes still meet patients' expectations. This study investigated
      whether treatment outcomes measured by patient-reported outcome measures fulfil
      patients' main expectations (i.e. decreased pain or improved functioning).
      METHODS: Patients who underwent hip or knee surgery in 20 Dutch hospitals in 2014
      were invited to a survey consisting of the KOOS Physical Function Short Form or
      the HOOS Physical Function Short Form, the NRS pain and the EQ-5D. Patients were
      asked their main reason for surgery and whether the expectations regarding this
      reason were fulfilled. RESULTS: A total of 2776 patients completed the survey.
      The most common reason for surgery was improved functioning (43.7%). Patients who
      were unable to choose between pain relief and improved functioning and patients
      who aimed for pain relief experienced more problems before surgery. However,
      patients who were unable to choose improved more than patients who wanted to
      improve their functioning on the NRS pain during use and the EQ-5D. More patients
      who aimed for pain relief felt that their expectations were fulfilled compared to
      other patients. CONCLUSIONS: Although an expectation for an outcome was not
      related to a greater improvement on that outcome, patient expectations were an
      indication of patients' improvement due to surgery. Differences in expectation
      fulfilment may be due to unrealistic expectations. To achieve optimal value,
      tailoring treatment using patient preferences and managing patient expectations
      is vital.

PMID- 29168165
TI  - Ergotamine Use and Overuse in Taiwan: A Retrospective Cohort Study.
AB  - OBJECTIVE: The aim of this study was to investigate the pattern of ergotamine
      prescription and overuse in Taiwan. BACKGROUND: Ergotamine is a frequently
      prescribed medication for the treatment of migraine, although excessive use may
      lead to medication-overuse headache. METHODS: We conducted a retrospective cohort
      study by using the Longitudinal Health Insurance Database 2005 in Taiwan.
      Patients enrolled in the study were between the ages of 18 and 80 years, received
      at least two prescriptions of ergotamine, and follow-up for more than 1 year at
      outpatient clinics during 1999 to 2013. Each ergotamine prescription was
      converted into a defined daily dose (DDD) and patients were sorted into two
      groups: occasional users, having fewer than 3 consecutive months of use, and
      regular users, with 3 consecutive months of use or more. Regular users were
      further divided into overusers (DDDs >= 10 per month) and non-overusers. RESULTS:
      A total of 41,023 migraine patients were enrolled in the study; 5803 patients
      were classified as regular users, with 859 of those being overusers. Of the
      ergotamine overusers, around 698/859 (82%) continued to use, and 443/859 (52%)
      remained overusers of ergotamine in the subsequent year after the index date. The
      most frequently prescribed prophylactic medications were propranolol and
      flunarizine, which were prescribed in 30.4% and 20.0% of overuse patients,
      respectively. CONCLUSIONS: Ergotamine overuse remains common in Taiwan, while
      prophylactic medicine is still underutilized. More education on ergotamine
      overuse headache is needed to improve awareness.

PMID- 29168166
TI  - New tool to tackle Alzheimer's disease: amyloid-beta protofibril-selective
      antibody AbSL: An Editorial Highlight for 'The conformational epitope for a new
      Abeta42 protofibril-selective antibody partially overlaps with the peptide N
      terminal region' on page 736.
AB  - This Editorial highlights a study by Colvin et al. (2017) in the current issue of
      Journal of Neurochemistry, in which the authors describe the development and
      characterisation of a new rabbit antibody (termed antibody St. Louis; AbSL) that
      preferentially recognises amyloid-beta (Abeta) protein 42 (Abeta42) protofibrils
      over other Abeta species.

PMID- 29168168
TI  - The value of cold storage whole blood platelets in trauma resuscitation is like
      real estate: a function of 'location, location, location'.

PMID- 29168167
TI  - Interdependent feedback regulation of breathing by the carotid bodies and the
      retrotrapezoid nucleus.
AB  - The retrotrapezoid nucleus (RTN) regulates breathing in a CO2 - and state
      dependent manner. RTN neurons are glutamatergic and innervate principally the
      respiratory pattern generator; they regulate multiple aspects of breathing,
      including active expiration, and maintain breathing automaticity during non-REM
      sleep. RTN neurons encode arterial PCO2 /pH via cell-autonomous and paracrine
      mechanisms, and via input from other CO2 -responsive neurons. In short, RTN
      neurons are a pivotal structure for breathing automaticity and arterial PCO2
      homeostasis. The carotid bodies stimulate the respiratory pattern generator
      directly and indirectly by activating RTN via a neuronal projection originating
      within the solitary tract nucleus. The indirect pathway operates under normo- or
      hypercapnic conditions; under respiratory alkalosis (e.g. hypoxia) RTN neurons
      are silent and the excitatory input from the carotid bodies is suppressed. Also,
      silencing RTN neurons optogenetically quickly triggers a compensatory increase in
      carotid body activity. Thus, in conscious mammals, breathing is subject to a dual
      and interdependent feedback regulation by chemoreceptors. Depending on the
      circumstance, the activity of the carotid bodies and that of RTN vary in the same
      or the opposite directions, producing additive or countervailing effects on
      breathing. These interactions are mediated either via changes in blood gases or
      by brainstem neuronal connections, but their ultimate effect is invariably to
      minimize arterial PCO2 fluctuations. We discuss the potential relevance of this
      dual chemoreceptor feedback to cardiorespiratory abnormalities present in
      diseases in which the carotid bodies are hyperactive at rest, e.g. essential
      hypertension, obstructive sleep apnoea and heart failure.

PMID- 29168169
TI  - Response to clobazam in continuous spike-wave during sleep.
AB  - AIM: To evaluate the efficacy of clobazam treatment in reducing epileptiform
      discharges and modifying neuropsychological function in continuous spike-wave
      during slow wave sleep. METHOD: We performed a prospective clinical trial in
      patients with continuous spike-wave during sleep aged 4 to 10 years. Patients
      underwent neuropsychological assessment and overnight electroencephalographic
      monitoring before treatment, and subsequent repeat assessment and overnight
      electroencephalographic monitoring 3 months after treatment. Treatment consisted
      of 1mg/kg clobazam up to a maximum dose of 30mg during the first night, followed
      by 0.5mg/kg nightly for 3 months. RESULTS: Nine patients completed the study and
      had pre- and post-neuropsychological evaluation. There was a qualitative
      reduction in median (p25 -p75 ) spike percentage after 3 months (72.2 [68.0-75.8]
      vs 32.7 [4.7-81.7]). There were no marked changes in median (p25 -p75 ) IQ
      comparing pre- and post-clobazam treatment (80.0 [74.0-88.0] vs 80.0 [67.0
      89.0]). There was a qualitative increase in Verbal IQ (83.0 [69.0-92.0] vs 95.0
      [83.0-99.0]) and a qualitative decrease in Non-verbal IQ (84.0 [74.0-87.0] vs
      71.0 [60.0-84.0]). INTERPRETATION: Qualitative improvements in epileptiform
      activity and cognition occurred in patients treated with clobazam for 3 months
      and the relationship between epileptiform activity and cognitive outcome should
      be studied in larger studies. WHAT THIS PAPER ADDS: Verbal IQ in patients with
      continuous spike-wave during sleep improved following short-term treatment with
      clobazam. Other neuropsychological improvements were observed, but varied by
      patient. Cognitive improvement was observed despite some worsening of
      epileptiform discharges.

PMID- 29168170
TI  - Platelets derived from fresh and cold-stored whole blood participate in clot
      formation in rats with acute traumatic coagulopathy.
AB  - The in vitro haemostatic functions of fresh whole blood (FWB) are well preserved
      after cold storage. This study aimed to determine whether platelets derived from
      FWB and stored whole blood (SWB) contribute to clot formation in tissue injury
      after transfusion into coagulopathic rats with polytrauma/haemorrhage (T/H). The
      rats were resuscitated 1 h after trauma with FWB or SWB collected from green
      fluorescence protein (GFP) transgenic rats. After transfusion, a liver incision
      was made and the tissue was collected 10 min after injury to identify GFP+
      platelets by immunohistochemistry. In comparison to FWB, platelet aggregation to
      adenosine diphosphate and protease-activated receptor-4 was reduced by 35% and
      20%, and clotting time was shortened by 25% in SWB. After transfusion, SWB led to
      a significant increase in platelet activation as measured by an elevation of
      CD62P and phosphatidylserine expression. The platelets from SWB were in a higher
      activation state, and showed higher clearance rate and formation of platelet
      leucocyte aggregates than those from FWB after transfusion. Platelets from both
      FWB and SWB were equivalently incorporated into the clot at the incisional site,
      as determined by co-localization of CD61 and GFP. This study suggests that SWB
      contributes to haemostatic function and is an effective alternative resource to
      treat trauma patients.

PMID- 29168172
TI  - Extracellular adenosine-induced Rac1 activation in pulmonary endothelium:
      Molecular mechanisms and barrier-protective role.
AB  - We have previously shown that Gs-coupled adenosine receptors (A2a) are primarily
      involved in adenosine-induced human pulmonary artery endothelial cell (HPAEC)
      barrier enhancement. However, the downstream events that mediate the
      strengthening of the endothelial cell (EC) barrier via adenosine signaling are
      largely unknown. In the current study, we tested the overall hypothesis that
      adenosine-induced Rac1 activation and EC barrier enhancement is mediated by Gs
      dependent stimulation of cAMP-dependent Epac1-mediated signaling cascades.
      Adenoviral transduction of HPAEC with constitutively-active (C/A) Rac1 (V12Rac1)
      significantly increases transendothelial electrical resistance (TER) reflecting
      an enhancement of the EC barrier. Conversely, expression of an inactive Rac1
      mutant (N17Rac1) decreases TER reflecting a compromised EC barrier. The adenosine
      induced increase in TER was accompanied by activation of Rac1, decrease in
      contractility (MLC dephosphorylation), but not Rho inhibition. Conversely,
      inhibition of Rac1 activity attenuates adenosine-induced increase in TER. We next
      examined the role of cAMP-activated Epac1 and its putative downstream targets
      Rac1, Vav2, Rap1, and Tiam1. Depletion of Epac1 attenuated the adenosine-induced
      Rac1 activation and the increase in TER. Furthermore, silencing of Rac1 specific
      guanine nucleotide exchange factors (GEFs), Vav2 and Rap1a expression
      significantly attenuated adenosine-induced increases in TER and activation of
      Rac1. Depletion of Rap1b only modestly impacted adenosine-induced increases in
      TER and Tiam1 depletion had no effect on adenosine-induced Rac1 activation and
      TER. Together these data strongly suggest that Rac1 activity is required for
      adenosine-induced EC barrier enhancement and that the activation of Rac1 and
      ability to strengthen the EC barrier depends, at least in part, on cAMP-dependent
      Epac1/Vav2/Rap1-mediated signaling.

PMID- 29168171
TI  - The arginine metabolome in acute lymphoblastic leukemia can be targeted by the
      pegylated-recombinant arginase I BCT-100.
AB  - Arginine is a semi-essential amino acid that plays a key role in cell survival
      and proliferation in normal and malignant cells. BCT-100, a pegylated (PEG)
      recombinant human arginase, can deplete arginine and starve malignant cells of
      the amino acid. Acute lymphoblastic leukemia (ALL) is the most common cancer of
      childhood, yet for patients with high risk or relapsed disease prognosis remains
      poor. We show that BCT-100 is cytotoxic to ALL blasts from patients in vitro by
      necrosis, and is synergistic in combination with dexamethasone. Against ALL
      xenografts, BCT-100 leads to a reduction in ALL engraftment and a prolongation of
      survival. ALL blasts express the arginine transporter CAT-1, yet the majority of
      blasts are arginine auxotrophic due to deficiency in either argininosuccinate
      synthase (ASS) or ornithine transcarbamylase (OTC). Although endogenous
      upregulation or retroviral transduced increases in ASS or OTC may promote ALL
      survival under moderately low arginine conditions, expression of these enzymes
      cannot prevent BCT-100 cytotoxicity at arginine depleting doses. RNA-sequencing
      of ALL blasts and supporting stromal cells treated with BCT-100 identifies a
      number of candidate pathways which are altered in the presence of arginine
      depletion. Therefore, BCT-100 provides a new clinically relevant therapeutic
      approach to target arginine metabolism in ALL.

PMID- 29168173
TI  - The role of melatonin on chemotherapy-induced reproductive toxicity.
AB  - OBJECTIVES: Reproductive malfunctions after chemotherapy still are a reason of
      reducing fertility and need specialized intensive care. The aim of this review
      was to investigate the effect of melatonin on the reproductive system under
      threatening with chemotherapeutic drugs. METHODS: To find the role of melatonin
      in the reproductive system during chemotherapy, a full systematic literature
      search was carried out based on Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines in the electronic databases up to 17 April 2017
      using search terms in the titles and abstracts. A total of 380 articles are
      screened according to our inclusion and exclusion criteria. Finally, 18 articles
      were included in this study. KEY FINDINGS: It has been cleared that melatonin has
      bilateral effects on reproductive cells. Melatonin protects normal cells via
      mechanisms, including decrease in oxidative stress, apoptosis, inflammation and
      modulating mitochondrial function, and sexual hormones. Furthermore, melatonin
      with antiproliferative properties and direct effects on its receptors improves
      reproductive injury and function during chemotherapy. On the other hand,
      melatonin sensitizes the effects of chemotherapeutic drugs and enhances
      chemotherapy-induced toxicity in cancerous cells through increasing apoptosis,
      oxidative stress and mitochondrial malfunction. CONCLUSIONS: The study provides
      evidence of the bilateral role of melatonin in the reproductive system during
      chemotherapy.

PMID- 29168175
TI  - Prognosis of status epilepticus in elderly patients.
AB  - PURPOSE: To evaluate the clinical features and prognosis of status epilepticus
      (SE) in patients above 70 years old. METHODS: Retrospective analysis of all
      patients >=70 years old with SE registered prospectively during 4 years. Follow
      up after discharge was performed. RESULTS: Ninety patients were evaluated. Acute
      symptomatic etiology was the most prevalent. The mean number of antiepileptic
      drugs (AEDs) used was 2.7 +/- 1.2, and 21% of the patients required sedation. A
      poor outcome was considered when death (31.1%) or developing of new neurological
      impairment at discharge (32.2%) occurred. After multivariate analysis, four
      variables predicted a poor outcome: acute symptomatic etiology (OR: 6.320; 95%
      CI: 1.976-20.217; P = .002), focal motor SE type (OR: 9.089; 95% CI: 2.482
      33.283; P = .001), level of consciousness (OR: 4.596; 95% CI: 1.903-11.098; P =
      .001), and SE duration >12 hours (OR: 3.763; 95% CI: 1.130-12.530; P = .031).
      Independent predictive factors of mortality were SE duration >12 hours (OR:
      4.306; 95% CI: 1.044-17.757; P = .043), modified Status Epilepticus Severity
      Score (mSTESS) (OR: 2.216; 95% CI: 1.313-3.740; P = .003), and development of
      complications (OR: 3.334; 95% CI: 1.004-11.070, P = .049). Considering long-term
      mortality, age (HR 1.036; 95% CI 1.001-1.071; P = .044), a potentially fatal
      underlying cause (HR 2.609; 95% CI 1.497- 4.548; P = .001), and mSTESS score >4
      (HR 1.485; 95% CI 1.158-1.903; P = .002) remained as predictive factors. There
      was no association between sedation and the number of AEDs used with outcome at
      discharge or long-term mortality (P > .05). CONCLUSIONS: SE above 70 years old
      has a high morbimortality. Prognosis is not related to treatment aggressiveness.

PMID- 29168176
TI  - A meta-analysis of the relationship between rational beliefs and psychological
      distress.
AB  - OBJECTIVE:  Rational emotive behavior therapy (REBT) model of psychological
      health assumes that rational beliefs cause functional emotions and adaptive
      behavior, but the presumed role of rational beliefs as protective factor against
      psychological distress/disorders is still in debate. An important step in
      validating an evidence-based therapy is to investigate the underling theoretical
      assumptions. Thus, the aim of the present meta-analysis is to investigate the
      direction and magnitude of the relationship between rational beliefs and
      psychological distress. METHOD:  Our search identified 26 studies that met our
      criteria. We evaluated the effect size using the random-effects model and we
      tested the moderator role of several variables. RESULTS: The overall results
      revealed a medium negative association between rational beliefs and psychological
      distress, r = -0.31. The strongest association was found for unconditional
      acceptance beliefs (r = -0.41). CONCLUSION: The results add empirical evidence
      for the underling theory of REBT and revealed that the strength of the
      association between rational beliefs and distress is robust for a wide range of
      emotional problems. Therefore, rational beliefs could be a trans-diagnostic
      protective factor against distress. Moreover, results emphasized that rational
      beliefs type is an important factor, suggesting an increased focus in therapy on
      the developing of unconditional acceptance and self-acceptance beliefs.

PMID- 29168174
TI  - Genetic variants in the platelet-derived growth factor subunit B gene associated
      with pancreatic cancer risk.
AB  - The platelet-derived growth factor (PDGF) signaling pathway plays important roles
      in development and progression of human cancers. In our study, we aimed to
      identify genetic variants of the PDGF pathway genes associated with pancreatic
      cancer (PC) risk in European populations using three published genome-wide
      association study datasets, which consisted of 9,381 cases and 7,719 controls.
      The expression quantitative trait loci (eQTL) analysis was also performed using
      data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified
      two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated
      with PC risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16,
      and p = 4.70 * 10-5 for the rs5757573 C allele and 1.21, 1.11-1.32, and 2.01 * 10
      5 for the rs6001516 T allele]. Haplotype analysis revealed that the C-T haplotype
      carriers had a significantly increased risk of PC than those carrying the T-C
      haplotype (OR = 1.23, 95% CI = 1.12-1.34, p =5.00 * 10-6 ). The multivariate
      regression model incorporating the number of unfavorable genotypes (NUGs) with
      age and sex showed that carriers with 1-2 NUGs, particularly among 60-70 age
      group or males, had an increased risk of PC, compared to those without NUG.
      Furthermore, the eQTL analysis revealed that both loci were correlated with a
      decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and
      pancreatic tumor tissues (p = 0.015 and 0.071, respectively). Our results suggest
      that genetic variants in PDGFB may play a role in susceptibility to PC. Further
      population and functional validations of our findings are warranted.

PMID- 29168177
TI  - Tumor characteristics and prognosis in women with pregnancy-associated breast
      cancer.
AB  - There is evidence of poor prognosis in women with pregnancy-associated breast
      cancer (PABC) diagnosed during pregnancy or within 2 years of delivery. Using a
      large, population-based cohort, we examined clinicopathologic features and
      survival in women with PABC. A cohort of women diagnosed with invasive breast
      cancer between 1992 and 2009 at ages 15-44 years was identified in the Swedish
      Cancer Register and the Breast Cancer Quality Registers. Dates of childbirths for
      each woman were retrieved from the Swedish Multi-Generation Register. Age
      standardized distributions of tumor stage (tumor size, nodal status, metastasis),
      Elston grade and ER/PR/HER2 status were compared between nulliparous women and
      women with breast cancer during pregnancy and up to 10 years postdelivery.
      Adjusted hazard ratios for all-cause mortality rates among patients were
      estimated using Cox regression. We identified 1,661 nulliparous women with breast
      cancer, 778 women with PABC (97 during pregnancy, 270 within first and 411 within
      second year postdelivery) and 3,598 during 2-10 years postdelivery. Compared to
      nulliparous women, women with PABC, and especially women diagnosed 0-12 months
      after delivery, had more advanced T and N stage, and higher proportions of ER/PR
      negative, HER2 positive and triple-negative tumors. Increased hazard ratios were
      observed in women diagnosed within 5 years of delivery after adjustment for age,
      year, education and region. Following additional adjustment for tumor
      characteristics, the hazard ratios were attenuated and nonsignificant. The poorer
      prognosis observed in women with PABC appears to be largely explained by more
      adverse tumor characteristics at diagnosis.

PMID- 29168178
TI  - The development of neuromotor skills and hand preference during infancy.
AB  - Assessing infant handedness has been controversial. Different assessment
      techniques and theoretical approaches produce different results. Evidence from a
      dynamic systems perspective showed that the development of postural control
      during infancy affects the expression of an infant's handedness. However, others
      found that developmental changes in postural control influenced the amount of
      symmetrical (bimanual) reaching during infancy, but not hand preference. Since
      most studies of infant handedness use age to assess development, perhaps measures
      of an infant's developing neuromotor control, irrespective of age, would better
      predict changes in an infant's hand preference. To assess neuromotor development,
      items from [Touwen's (1976) Neurological development in infancy. Lavenham,
      Suffolk: The Lavenham Press, LTD]. "Group III" indices were used. These items
      assess developmental changes in neuromotor abilities throughout the 6-14-month
      age period. Hand preference for acquiring objects was measured during these same
      months. Group Based Trajectory Models (GBTM) of 380 infants identified four
      different groups of infants according to the trajectory of the development of
      their hand preferences (32% Early Right, 12% Early Left, 25% Late Right, 30% No
      Preference). A multilevel model was used to compare these four developmental
      trajectories according to age and neuromotor development. Age, not neuromotor
      development, is a better predictor of differences in developmental trajectories
      of the four hand preference groups. However, Late Right infants are significantly
      less developed at 6 months than No Preference, Early Right and Left infants and
      both Early Right and Left infants are most advanced at 6 months. All groups
      exhibit similar rates of neuromotor development indicating no "catch-up" by the
      Late Right infants. Thus, any assessment of infant handedness will incorporate
      necessarily four groups of infants with differently developing hand preferences
      and neuromotor abilities.

PMID- 29168179
TI  - Phenolic and physicochemical stability of a functional beverage powder mixture
      during storage: effect of the microencapsulant inulin and food ingredients.
AB  - BACKGROUND: The need for a convenience herbal iced tea product with reduced
      kilojoules merited investigation of the shelf-life of powder mixtures containing
      a green Cyclopia subternata Vogel (honeybush) extract with proven blood glucose
      lowering activity and alternative sweetener mixture. RESULTS: Prior to long-term
      storage testing, the wettability of powder mixtures containing food ingredients
      and the compatibility of their components were confirmed using the static sessile
      drop method and isothermal microcalorimetry, respectively. The powders packed in
      semi-sealed containers remained stable during storage at 25  degrees C/60%
      relative humidity (RH) for 6 months, except for small losses of specific phenolic
      compounds, namely mangiferin, isomangiferin, 3-beta-d
      glucopyranosyliriflophenone, vicenin-2 and 3',5'-di-beta-d
      glucopyranosylphloretin, especially when both citric acid and ascorbic acid were
      present. These acids drastically increased the degradation of phenolic compounds
      under accelerated storage conditions (40  degrees C/75% RH). Accelerated storage
      also caused changes in the appearance of powders and the colour of the
      reconstituted beverage solutions. Increased moisture content and aw of the
      powders, as well as moisture released due to dehydration of citric acid
      monohydrate, contributed to these changes. CONCLUSION: A low-kilojoule honeybush
      iced tea powder mixture will retain its functional phenolic compounds and
      physicochemical properties during shelf-life storage at 25  degrees C for 6
      months. (c) 2017 Society of Chemical Industry.

PMID- 29168180
TI  - CXCR2 is critical for bacterial control and development of joint damage and pain
      in Staphylococcus aureus-induced septic arthritis in mouse.
AB  - Staphylococcus aureus is the main pathogen associated with septic arthritis. Upon
      infection, neutrophils are quickly recruited to the joint by different
      chemoattractants, especially CXCR1/2 binding chemokines. Although their excessive
      accumulation is associated with intense pain and permanent articular damage,
      neutrophils have an important function in controlling bacterial burden. This work
      aimed to study the role of CXCR2 in the control of infection, hypernociception
      and tissue damage in S. aureus-induced septic arthritis in mice. The kinetics of
      neutrophil recruitment correlated with the bacterial load recovered from inflamed
      joint after intra-articular injection of S. aureus. Treatment of mice from the
      start of infection with the non-competitive antagonist of CXCR1/2, DF2156A,
      reduced neutrophil accumulation, cytokine production in the tissue, joint
      hypernociception and articular damage. However, early DF2156A treatment increased
      the bacterial load locally. CXCR2 was important for neutrophil activation and
      clearance of bacteria in vitro and in vivo. Start of treatment with DF2156A 3
      days after infection prevented increase in bacterial load and reduced the
      hypernociception in the following days, but did not improve tissue damage. In
      conclusion, treatment with DF2156A seems be effective in controlling tissue
      inflammation and dysfunction but its effects are highly dependent on the timing
      of the treatment start.

PMID- 29168182
TI  - Improving research in women's health in Nordic countries: challenges and
      opportunities ahead.

PMID- 29168181
TI  - Different interleukin-17-secreting Toll-like receptor+ T-cell subsets are
      associated with disease activity in multiple sclerosis.
AB  - Signalling through Toll-like receptors (TLRs) may play a role in the pathogenesis
      of autoimmune diseases, such as multiple sclerosis (MS). In the present study,
      the expression of TLR-2, -4 and -9 was significantly higher on CD4+ and CD8+ T
      cells from MS patients compared to healthy individuals. Following in-vitro
      activation, the proportion of interleukin (IL)-17+ and IL-6+ CD4+ and CD8+ T
      cells was higher in the patients. In addition, the proportion of IFN-gamma
      secreting TLR+ CD8+ T-cells was increased in MS patients. Among different IL-17+
      T-cell phenotypes, the proportion of IL-17+ TLR+ CD4+ and CD8+ T-cells producing
      IFN-gamma or IL-6 were positively associated with the number of active brain
      lesions and neurological disabilities. Interestingly, activation of purified CD4+
      and CD8+ T-cells with ligands for TLR-2 (Pam3Csk4), TLR-4 [lipopolysaccharide
      (LPS)] and TLR-9 [oligodeoxynucleotide (ODN)] directly induced cytokine
      production in MS patients. Among the pathogen-associated molecular patterns
      (PAMPs), Pam3Csk4 was more potent than other TLR ligands in inducing the
      production of all proinflammatory cytokines. Furthermore, IL-6, IFN-gamma, IL-17
      and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels produced by
      Pam3Csk4-activated CD4+ cells were directly associated with disease activity. A
      similar correlation was observed with regard to IL-17 levels released by Pam3Csk4
      stimulated CD8+ T-cells and clinical parameters. In conclusion, our data suggest
      that the expansion of different T helper type 17 (Th17) phenotypes expressing TLR
      2, -4 and -9 is associated with MS disease activity, and reveals a preferential
      ability of TLR-2 ligand in directly inducing the production of cytokines related
      to brains lesions and neurological disabilities.

PMID- 29168183
TI  - Effectiveness of gastrostomy for improving nutritional status and quality of life
      in patients with epidermolysis bullosa: a systematic review.
AB  - Individuals with epidermolysis bullosa (EB) may present with a broad spectrum of
      growth impairment and multiorgan disorders, with compromised nutritional status
      and quality of life. The provision of nutrients through a gastrostomy tube may
      minimize EB-related malnourishment but may also result in skin injuries and
      infections. In this systematic review we consider the current evidence about the
      effectiveness of gastrostomy in restoring nutritional status and improving
      quality of life in patients with EB. Seven studies (n = 146) met selection
      criteria and patients ranged in age from 6 weeks to 33 years of age. Although it
      is not a risk-free procedure, the placement of a gastrostomy tube is a feasible
      and safe alternative to provide nutritional support and to improve the quality of
      life of patients.

PMID- 29168184
TI  - Effect of ultra-superheated steam on aflatoxin reduction and roasted peanut
      properties.
AB  - BACKGROUND: Aflatoxins are carcinogenic toxins produced by Aspergillus flavus and
      Aspergillus parasiticus that are found naturally in peanut. It requires extremely
      high temperatures to eliminate aflatoxins from the nuts. The aims of this study
      were to investigate the effect of ultra-superheated steam (USS) on the reduction
      of aflatoxin B1 (AFB1 ) accompanying the roasting process and to determine
      roasted peanut qualities that affected consumer acceptance. RESULTS: Whole peanut
      kernels were intentionally contaminated by AFB1 standard solution at the level of
      50 +/- 10 ug kg-1 before subjecting to USS treatment at 300-400  degrees C
      between 10 and 80 s. The high temperature of USS could significantly decrease
      AFB1 level to 9.83 +/- 3.51, 15.33 +/- 2.23 and 8.95 +/- 2.32 ug kg-1 when 300 
      degrees C for 80 s, 350  degrees C for 40 s and 400  degrees C for 40 s were
      employed, respectively. AFB1 was reduced as much as 83.86 +/- 2.66% when 400 
      degrees C for 40 s was applied. The moisture content of treated peanuts was
      decreased to less than 3% and browning index was developed from 30.96 +/- 1.59 to
      95.76 +/- 7.23. CONCLUSION: Higher roasting degree was obtained according to the
      increase in browning index. Oil quality showed that peroxide values and acid
      values were greatly below the allowance level. USS could effectively decrease
      AFB1 and render expectable roasting qualities of peanut. (c) 2017 Society of
      Chemical Industry.

PMID- 29168185
TI  - YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by
      regulating the CDKN3/MdM2/P53/P21 signaling pathway.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the malignant lethal tumors. It
      has been reported that the transcriptional regulator Yin Yang-1 (YY1) suppressed
      the invasion and metastasis of PDAC. However, the function of YY1 on
      proliferation and migration of pancreatic cancer remains to be clarified. In this
      study, we found that YY1 overexpression or knockdown can inhibit or promote the
      proliferation and migration of pancreatic cancer cells. Digital gene expression
      sequencing indicates that cyclin-dependent kinase inhibitor 3 (CDKN3) may be the
      candidate target gene of YY1. Then we found that YY1 can downregulate the
      expression of CDKN3 by directly binding to the promoter region of CDKN3.
      Silencing CDKN3 expression could inhibit the ability of cell proliferation and
      migration and overexpression of CDKN3 could restore the effects induced by YY1
      overexpression in pancreatic cancer cells. The expression levels of YY1 and CDKN3
      were negatively correlated in pancreatic cancer tissues and PDAC patients with
      higher levels of CDKN3 have poor prognosis. Vitro and vivo study show that CDKN3
      can form a complex with MdM2-P53, thus leading to inhibiting the expression of
      P21, which is the target gene of P53, and finally facilitates the cell cycle to
      promote the proliferation of pancreatic cancer cells. Hence, YY1 can directly
      regulate the expression of CDKN3 and participate in the cycle of pancreatic
      cancer cells, which can inhibit the progression of pancreatic cancer. These
      results reveal that YY1-CDKN3-MDM2/P53-P21 axis is involved in pancreatic
      tumorigenesis, which may develop new methods for human pancreatic cancer therapy.

PMID- 29168187
TI  - Storage time of platelet concentrates and risk of a positive blood culture: a
      nationwide cohort study.
AB  - BACKGROUND: Concern of transfusion-transmitted bacterial infections has been the
      major hurdle to extend shelf life of platelet (PLT) concentrates. We aimed to
      investigate the association between storage time and risk of positive blood
      cultures at different times after transfusion. STUDY DESIGN AND METHODS: We
      performed a nationwide cohort study among PLT transfusion recipients in Denmark
      between 2010 and 2012, as recorded in the Scandinavian Donations and Transfusions
      (SCANDAT2) database. Linking with a nationwide database on blood cultures (MiBa),
      we compared the incidence of a positive blood culture among recipients of PLTs
      stored 6 to 7 days (old) to those receiving fresh PLTs (1-5 days), using Poisson
      regression models. We considered cumulative exposures in windows of 1, 3, 5, and
      7 days. RESULTS: A total of 9776 patients received 66,101 PLT transfusions. The
      incidence rate ratio (IRR) of a positive blood culture the day after transfusion
      of at least one old PLT concentrate was 0.77 (95% confidence interval [CI], 0.54
      1.09) compared to transfusion of fresh PLT concentrates. The incidence rate of a
      positive blood culture was lower the day after receiving one old compared to one
      fresh PLT concentrate (IRR, 0.57; 95% CI, 0.37-0.87). Three, 5, or 7 days after
      transfusion, storage time was not associated with the risk of a positive blood
      culture. CONCLUSION: Storage of buffy coat-derived PLT concentrates in PAS-C up
      to 7 days seems safe regarding the risk of a positive blood culture. If anything,
      transfusion of a single old PLT concentrate may decrease this risk the following
      day.

PMID- 29168188
TI  - The relationship between social play and developmental milestones in wild
      chimpanzees (Pan troglodytes schweinfurthii).
AB  - Social play is common among many group-living animals, but the benefits are not
      well understood. Proposed benefits include increased muscle coordination as the
      result of increased locomotor versatility and development, and strengthened
      social bonds through interactions with like-aged individuals. In this study, we
      used 33 years of long-term behavioral data on infant chimpanzees in Gombe
      National Park, Tanzania, to examine these potential benefits of social play,
      specifically how the percentage of time engaged in social play relates to motor
      and social developmental milestones. We predicted that infants who engaged in
      more social play would achieve motor and social milestones at younger ages. We
      found that individuals that spent more time engaging in social play achieved the
      motor milestones of riding dorsally and traveling independently at earlier ages.
      Additionally, we found that the amount of play was correlated with earlier ages
      for reaching the social milestones of spatial independence from mother, first
      grooming of non-maternal kin, and first observed mating attempt. This is the
      first study in great apes to demonstrate a relationship between play behavior and
      developmental milestones, supporting the hypotheses that play provides motor, and
      social benefits.

PMID- 29168186
TI  - Adipokines and inflammation markers and risk of differentiated thyroid carcinoma:
      The EPIC study.
AB  - Other than the influence of ionizing radiation and benign thyroid disease, little
      is known about the risk factors for differentiated thyroid cancer (TC) which is
      an increasing common cancer worldwide. Consistent evidence shows that body mass
      is positively associated with TC risk. As excess weight is a state of chronic
      inflammation, we investigated the relationship between concentrations of leptin,
      adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis
      factor (TNF)-alpha and the risk of TC. A case-control study was nested within the
      European Prospective Investigation into Cancer and Nutrition (EPIC) study and
      included 475 first primary incident TC cases (399 women and 76 men) and 1,016
      matched cancer-free cohort participants. Biomarkers were measured in serum
      samples using validated and highly sensitive commercially available immunoassays.
      Odds ratios (ORs) of TC by levels of each biomarker were estimated using
      conditional logistic regression models, adjusting for BMI and alcohol
      consumption. Adiponectin was inversely associated with TC risk among women
      (ORT3vs.T1  = 0.69, 95% CI: 0.49-0.98, Ptrend  = 0.04) but not among men
      (ORT3vs.T1  = 1.36, 95% CI: 0.67-2.76, Ptrend  = 0.37). Increasing levels of IL
      10 were positively associated with TC risk in both genders and significantly so
      in women (ORT3vs.T1  = 1.59, 95% CI: 1.13-2.25, Ptrend  = 0.01) but not in men
      (ORT3vs.T1  = 1.78, 95% CI: 0.80-3.98, Ptrend  = 0.17). Leptin, CRP, IL-6 and TNF
      alpha were not associated with TC risk in either gender. These results indicate a
      positive association of TC risk with IL-10 and a negative association with
      adiponectin that is probably restricted to women. Inflammation may play a role in
      TC in combination with or independently of excess weight.

PMID- 29168189
TI  - Imaging mass spectrometry for novel insights into contact allergy - a proof-of
      concept study on nickel.
AB  - BACKGROUND: In spite of extensive regulation to limit exposure, nickel remains
      the main cause of contact allergy in the general population. More detailed
      knowledge on the skin uptake of haptens is required. So far, no method exists for
      the visualization of this clinically relevant hapten and its distribution in the
      skin. OBJECTIVES: To show, in terms of a proof of concept, that imaging mass
      spectrometry [time of flight secondary ion mass spectrometry (ToF-SIMS)] can be
      applied for investigation of the penetration and distribution of nickel in human
      skin. METHOD: Full-thickness human skin obtained from breast reduction surgery
      was exposed to nickel sulfate (5% in deionized water) for 24 h in Franz-type
      diffusion cells. Biopsies were obtained from nickel-treated samples and control
      (deionized water). The tissue was sliced, and analysed with ToF-SIMS, generating
      high-resolution images of ion distribution in the epidermis and upper dermis.
      RESULTS: The skin layers could be discerned from the ToF-SIMS data, particularly
      on the basis of the collagen signal. Nickel ions were localized to the stratum
      corneum and upper epidermis. CONCLUSIONS: This is the first time that ToF-SIMS
      has been applied to trace the distribution of a hapten in human skin. Proof of
      principle was shown for nickel, and the technique can, in the future, be expanded
      for investigation of the skin distribution of clinically relevant sensitizers in
      general.

PMID- 29168190
TI  - Innovative food products for cancer patients: future directions.
AB  - One of the main challenges for cancer patients under treatment is to prevent and
      tackle malnutrition. The current clinical nutrition market offers different food
      supplements or oral nutritional support products (mainly milkshakes or modified
      texture products) for cancer patients under risk of malnutrition. However, it is
      worth mentioning that these products do not address the pleasure of eating, since
      they do not meet sensory requirements, such as taste and smell alterations, nor
      patients' food preferences, leading to a big impact on their quality of life
      (QOL). Still, controversy remains regarding the specific nutritional requirements
      for cancer patients during the disease. Several randomized controlled clinical
      trials yield opposite results when using different bioactive compounds such as
      omega-3 fatty acids or antioxidants in order to prevent malnutrition or improve
      QOL. The use of 'omics' technologies in oncology, such as membrane lipidomics, as
      a powerful tool to provide new insights for the understanding of diet and cancer
      and their interacting metabolic pathways, will be discussed. The better knowledge
      of specific requirements (nutrients, sensory parameters and food preferences) for
      cancer patients provides valuable information for the food industry in the design
      of customized food products capable of preventing malnutrition, alleviating
      symptoms and improving QOL. (c) 2017 Society of Chemical Industry.

PMID- 29168191
TI  - Genetic variants in IL15 promoter affect transcription activity and intramuscular
      fat deposition in longissimus dorsi muscle of pigs.
AB  - Intramuscular fat (IMF) content is a key aspect of pork quality. Elucidation of
      intramuscular adipocyte regulation mechanisms is important for improving IMF
      content. Intramuscular adipocytes are dispersed among muscle fibers, so they are
      inclined to be affected by muscle-derived factors. Interleukin-15 is a major
      muscle-secreted factor. In this study, the genetic and physiological impacts of
      IL15 on adipogenesis is investigated. The promoter region of IL15 was scanned by
      comparative sequencing using two DNA pools of high- and low-IMF individuals. Two
      SNPs, c.-342C>T (ss2137497757) and c.-334G>A (ss2137497756) (the translation
      start site is designated as +1), were identified with reverse allele distribution
      in these two groups. Genotyping by allele-specific PCR revealed that the two SNPs
      were completely linked. The IMF content of TA/TA individuals was lower than that
      for CG/CG ones, whereas the IL15 expression level was higher in T-A/T-A
      individuals. Luciferase assaying also revealed that the T-A haplotype promoter
      had higher transcription activity. Meanwhile, the effect of interleukin-15 on
      adipocyte differentiation was further assessed in vitro. Results showed that
      interleukin-15 suppressed preadipocyte proliferation in a dose-dependent manner.
      The cell cycle of preadipocytes was arrested, and apoptosis was induced. Oil Red
      O staining and triglyceride quantification indicated that adipocyte
      differentiation was also inhibited by interleukin-15. The mRNA levels of PPARG
      and FABP4 decreased markably upon interleukin-15 treatment. Taken together, we
      identified two completely linked SNPs in the porcine IL15 promoter region that
      could alter IL15 transcription activity. As interleukin-15 can inhibit porcine
      adipocyte differentiation, these promoter mutations could affect IMF deposition
      by producing differential levels of muscle-derived interleukin-15.

PMID- 29168192
TI  - Seeing it differently: self-reported description of vision loss in dry age
      related macular degeneration.
AB  - PURPOSE: A realistic description of visual symptoms associated with dry age
      related macular degeneration (AMD) is important for raising awareness of the
      condition and educating patients. This study aimed to develop a set of
      descriptors for dry AMD and examine the realism of images currently and
      frequently used to show visual symptoms of the condition. METHODS: Volunteers
      with dry AMD with a range of disease severity were given an eye examination and
      were asked to describe visual symptoms of their condition in a conversational
      interview. Participants were also asked to comment on a photograph typically used
      to portray the visual symptoms of AMD. Interviews were audio recorded,
      transcribed and subjected to content analysis. RESULTS: Twenty-nine participants
      were interviewed. Median (interquartile range [IQR]) age was 75 (70, 79) years.
      Median (IQR) binocular visual acuity (VA) and Pelli-Robson contrast sensitivity
      (CS) was 0.2 (0.18, 0.36) logMAR and 1.65 (1.50, 1.95) log CS respectively.
      Three, 17 and nine patients had early, intermediate and late (geographic atrophy,
      GA) AMD, respectively. The most frequently reported descriptor group was blur (n
      = 13) followed by missing (n = 10) and distortion (n = 7). We chose the most
      popular image used to portray the visual symptoms of dry AMD based on an internet
      search and showed this to 21 participants. Sixteen participants (76% [95%
      confidence interval 53-92%]), including three out of the seven people with
      geographic atrophy, unequivocally rejected the realism of the image. CONCLUSIONS:
      People with dry AMD use a wide range of descriptors for their visual experience.
      Visual symptoms of dry AMD as portrayed by commonly shown images were not the
      experience of most people in this study.

PMID- 29168193
TI  - The Effects of Long-Term Varenicline Administration on Ethanol and Sucrose
      Seeking and Self-Administration in Male P Rats.
AB  - BACKGROUND: Varenicline, a partial agonist at alpha4beta2 and full agonist at
      alpha7 nicotinic cholinergic receptors, is FDA-approved for treatment of smoking
      cessation and has been found to reduce alcohol craving in clinical populations.
      In rodents, varenicline decreases free-choice ethanol (EtOH) intake with somewhat
      mixed findings in operant paradigms that utilize a combined
      appetitive/consummatory response. METHODS: The present experiment utilized an
      operant paradigm that procedurally separates appetitive from consummatory
      responding and a "reward-blocking" approach (i.e., rats were able to consume EtOH
      during treatment) to better understand the efficacy of varenicline as a treatment
      for EtOH self-administration and subsequent EtOH seeking. Separate groups of EtOH
      and sucrose-reinforced alcohol-preferring, male P rats experienced alternating
      cycles of vehicle (2-week cycles) and varenicline (0.3, 1.0, and 2.0 mg/kg self
      administered in a gelatin preparation) treatment (3-week cycles) prior to daily
      sessions where a single lever press resulted in 20 minutes of reinforcer access.
      At the end of each cycle, a single extinction session assessed the seeking
      response in the absence of drug pretreatment. RESULTS: Varenicline dose
      dependently decreased EtOH intake. Sucrose intake was largely unaffected, with no
      overall treatment effects and only sporadic days where the medium and high dose
      differed from vehicle. Neither sucrose nor EtOH seeking was significantly
      decreased by varenicline, and there were no treatment effects on either lick or
      lever-press latency. Overall effect sizes were much greater for both drinking and
      seeking in the EtOH group as compared to the sucrose group. CONCLUSIONS:
      Varenicline effectively attenuates EtOH self-administration during treatment, but
      the experience with EtOH consumption while varenicline is "on board" is not
      sufficient to alter subsequent EtOH seeking. The overall pattern of findings
      indicates that varenicline blocks the rewarding properties of EtOH while not
      substituting for EtOH, that the nonspecific effects on an alternate reinforcer
      are negligible, and that blood levels of varenicline need to be maintained in
      order for treatment to remain effective.

PMID- 29168194
TI  - Retinal putative glial alterations: implication for glaucoma care.
AB  - PURPOSE: Gliosis-like retinal alterations, presumed to be activated retinal
      astrocytes and Muller cells (ARAM), have been reported to occur frequently in
      patients with glaucoma but rarely in controls. We investigated the association
      between glaucomatous abnormality and the presence, the extent of retinal region,
      and the spatial distribution, of hyperreflective retinal alterations on optical
      coherence tomography (OCT) en-face images, presumed to be ARAM. METHODS: Findings
      of hyperreflective structures, presumed to be ARAM, in the central retinal +/-24
      degrees of OCT en-face images (acquired with the SPECTRALIS(r) OCT) were compared
      between 35 younger controls, 42 older controls and 38 patients with glaucoma.
      Presumed ARAM was defined as reflective structures on the en-face images other
      than retinal vasculature and retinal nerve fibre bundles. Chi-square tests were
      used to compare the proportion of younger controls vs older controls with
      presumed ARAM to investigate the effect of ageing, and the proportion of patients
      vs age-similar older controls with presumed ARAM to investigate the effect of
      disease. We also investigated the effect of glaucoma on the retinal area with
      presumed ARAM when it was present; we used an analysis of covariance (ancova) to
      compare the retinal area with hyperreflectivity in patients vs controls,
      adjusting for the effects of age and axial length. RESULTS: The mean (S.D.) age
      of the younger controls, older controls, and patients with glaucoma was 26 (3),
      62 (10) and 69 (8) years, respectively. The median (25th quartile, 75th quartile)
      of the retinal region with the hyperreflective structures, presumed to be ARAM,
      was zero (0,0), 1 (0,6), and 11 (0,43) degrees square in the younger controls,
      older controls and patients with glaucoma respectively. The chi-square test
      investigating the effect of ageing found chi2 (1, N = 77) = 24.8, p < 0.001, and
      that investigating the effect of disease found chi2 (1, N = 80) = 2.3, p = 0.1.
      The ancova found F(1, 46) = 10.32, P = 0.02. CONCLUSIONS: There was an effect of
      ageing on the presence of the hyperreflective structures, presumed to be ARAM, on
      OCT images. Compared to the presence of hyperreflective structures, the extent of
      retinal region with the hyperreflective structures has a greater potential of
      being an indicator of glaucomatous degeneration. Further study is needed to
      investigate the nature of the relation between glaucomatous abnormality and the
      extent of the retina with the hyperreflective structures, presumed to be ARAM.

PMID- 29168195
TI  - For whom we forgive matters: relationship focus magnifies, but self-focus buffers
      against the negative effects of forgiving an exploitative partner.
AB  - Increasingly, studies indicate that victims experience negative outcomes after
      forgiving offenders who present an exploitation risk. However, we demonstrate
      that the link between exploitation risk and forgiveness-related outcomes is
      dependent upon a victim's focus of forgiving. Two studies, the first employing a
      prospective design (N = 110) and the second an experimental scenario method (N =
      261), replicate previous research on the negative effects of exploitation risk
      and also test two new hypotheses. First, we found that forgiving explicitly for
      the sake of a relationship is associated with greater distress, relative to
      deciding to forgive for the sake of the self. Second, we found that relationship
      focussed forgiveness magnified the distress caused by exploitation risk, whereas
      self-focussed forgiveness, relative to relationship-focussed forgiveness,
      provides a buffer against it. In short, these findings demonstrate that for whom
      we forgive matters. We discuss theoretical and practical implications for
      understanding when forgiving is costly.

PMID- 29168196
TI  - Family members' expectations regarding nurses' competence in care homes: a
      qualitative interview study.
AB  - BACKGROUND: Structural and cultural changes in the care of older people have
      influenced nursing practice, creating a need to identify current competency
      requirements for nurses working in care homes. Family members have an important
      role in ensuring the well-being of older people living in care homes, and family
      members' can provide valuable information about competence requirements. AIM: To
      explore the expectations of the care home residents' family members regarding the
      competence of nurses in care homes for older people. METHODS: A qualitative
      descriptive design was used. Semi-structured interviews were conducted with 18
      care home residents' family members between March and September 2016.
      Participants were recruited with help from regional associations and member
      associations of The Central Association of Carers in Finland and from regional
      associations of The Alzheimer's Society of Finland. The snowball technique was
      also used. The data were analysed using inductive content analysis. ETHICS:
      Ethics committee approval was obtained from the university committee on research
      ethics, and written informed consent was obtained from participants. FINDINGS:
      The care home residents' family members expected that nurses would be able to
      interact with and treat people respectfully. Reflective collaboration between the
      nurse and a family member was also emphasised. Family members expected nurses to
      provide high-quality basic care and nursing and support residents' well-being
      individually and holistically. CONCLUSIONS: Family members' expectations reflect
      the need for ethical and interactional competence in the care home. In addition,
      evidence-based practice competencies are required to provide high-quality care.
      Nurses' ability to provide person-centred, individual and holistic care is vital
      to ensure care home residents' well-being.

PMID- 29168197
TI  - Mechanism of increased microbial autofluorescence by heat treatment.
AB  - : The total direct count (TDC) microbial enumeration method is rapid and suitable
      for analysing environmental samples containing numerous un-culturable micro
      organisms. Conventional TDC methods require the addition of a fluorescent stain
      and are thus unsuitable for automatic monitoring. We unexpectedly found that
      heated micro-organisms emit strong autofluorescence. This study was conducted to
      determine how heating enhances the autofluorescence of bacteria and fungi and to
      evaluate whether the phenomenon could be exploited to develop a new TDC method.
      Bacterial autofluorescence was augmented by heating cells at 200 degrees C. ELISA
      results indicated that levels of advanced glycation end products (AGEs) increased
      in heated microbes. Catechin, an inhibitor of the Maillard reaction, disrupted
      the intensification of autofluorescence. These results suggest that the enhanced
      autofluorescence is associated with the formation of AGEs and that the reaction
      could be utilized as alternative probe in TDC methods. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Autofluorescence of bacteria and fungi was prominently intensified by
      heat treatment at 200 degrees C. This phenomenon was associated with advanced
      glycation end products formed in micro-organisms via the Maillard reaction. The
      fluorescence signal was strong enough to be utilized as an alternative probe for
      fluorescent dye in the total direct count method. This phenomenon could be
      incorporated in an automatic apparatus for microbial enumeration, as it does not
      require staining.

PMID- 29168198
TI  - PERK leads a hub dictating pancreatic beta cell homoeostasis.
AB  - In humans, the pathogenesis of diabetes is characterised by two major pancreatic
      beta cell defects: a reduction in beta cell mass and the failure of beta cells to
      produce enough insulin. Over the past two decades, multiple studies involving
      cell cultures, animal models and human subjects have established the importance
      of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) in the
      adaptive functional capacity of pancreatic beta cells during embryonic
      development and into adulthood. In this review, we will highlight major findings
      identifying PERK as a crucial player in beta cell physiology and in diabetes.

PMID- 29168199
TI  - Experimental Investigation of Left Ventricular Flow Patterns After Percutaneous
      Edge-to-Edge Mitral Valve Repair.
AB  - Mitral valve percutaneous edge-to-edge repair (PEtER) is a viable solution in
      high-risk patients with severe symptomatic mitral regurgitation. However, the
      generated double-orifice configuration poses challenges for the evaluation of the
      hemodynamic performance of the mitral valve and may alter flow patterns in the
      left ventricle (LV) during diastole. This in vitro study aims to evaluate the
      hemodynamic modifications following a simulated PEtER. A custom-made mitral valve
      was developed, and two configurations were tested: (i) a single-orifice valve
      with mitral regurgitation and (ii) a double-orifice mitral valve configuration
      following PEtER. The hemodynamic performance of the valve was evaluated using
      Doppler echocardiography and catheterization, while the flow patterns in the LV
      were investigated using particle image velocimetry (PIV). The tests were run at a
      stroke volume of 65 mL and a heart rate of 70 bpm. PEtER was found to
      significantly reduce the regurgitant volume (15 vs. 34 mL). There was a good
      agreement between Doppler and catheter transmitral pressure gradients (peak
      gradient: 9 vs. 7 mm Hg; mean gradient: 4 vs. 3 mm Hg) as well as an excellent
      agreement between maximal velocity measured by Doppler and PIV (1.60 vs. 1.58
      m/s). Vortex development in the LV during diastole was significantly different
      after repair. PEtER significantly increased the amplitude of Reynolds and viscous
      shear stresses, as well as the number of high shear regions in the LV,
      potentially promoting thromboembolism events.

PMID- 29168200
TI  - The moderating role of job resources in the relationship between job demands and
      interleukin-6 in an Italian healthcare organization.
AB  - In this study we examined the association between job demands (JD), job resources
      (JR), and serum levels of a possible biomarker of stress, the pro-inflammatory
      cytokine interleukin-6 (IL-6). According to the buffer hypothesis of the Job
      Demands-Resources (JD-R) model, we expected that job resources-defined as job
      autonomy and social support from supervisor-might buffer the relationship between
      job demands, defined as emotional demands and interpersonal conflict with
      colleagues, and IL-6. Data from 119 employees in an Italian public healthcare
      organization (acute care hospital) were analyzed using multiple regression. In
      predicting IL-6, the interactions between emotional demands and JR and between
      interpersonal conflict with colleagues and job autonomy (but not social support)
      were significant, after controlling for the effect of age and gender. The
      association between JD and IL-6 was stronger for individuals with low levels of
      JR, so that levels of IL-6 were highest when JD were high and JR were low.
      Overall, these results are consistent with the buffer hypothesis of the JD-R
      model and also extend previous research, showing that the exposure to stressful
      situations at work, measured as high JD and low JR, is associated with higher
      levels of IL-6 in hospital employees.

PMID- 29168201
TI  - Modification of pomological characteristics and flavour components of fruits and
      virgin olive oil following wastewater irrigation and soil tillage.
AB  - BACKGROUND: The experiment was carried out on olive trees cv. Chemlali, during
      two successive years (2013/2014). Two irrigation treatments (IT: Trees irrigated
      with wastewater; TRC: Trees grown under rainfed condition) were combined with two
      tillage practices (TTS: Trees grown in tilled soil; TNTS: Trees grown in non
      tilled soil). RESULTS: The results of the study showed that wastewater irrigation
      combined with soil tillage improved the pomological characteristics of olive
      fruits. The tree yield increase was substantial for IT and TTS. However, most of
      the identified phenolic compounds, especially oleuropein, mainly accumulated in
      olive fruits of the TC block (TNTS + TRC), suggesting a marked improvement in the
      nutritional value of these fruits. Moreover, fruits of TNTS had high contents of
      sugar compounds, required for the synthesis of the fruit storage material. The
      study also showed that the agronomic practices affected the amounts of some
      aromatic compounds responsible for the distinctive flavour notes of olive oil.
      CONCLUSION: Agronomic practices may affect considerably the commercial and
      nutritional values and the sensorial quality of the commodities. (c) 2017 Society
      of Chemical Industry.

PMID- 29168202
TI  - Differentiation of Ecuadorian National and CCN-51 cocoa beans and their mixtures
      by computer vision.
AB  - BACKGROUND: Ecuador exports two major types of cocoa beans, the highly regarded
      and lucrative National, known for its fine aroma, and the CCN-51 clone type, used
      in bulk for mass chocolate products. In order to discourage exportation of
      National cocoa adulterated with CCN-51, a fast and objective methodology for
      distinguishing between the two types of cocoa beans is needed. RESULTS: This
      study reports a methodology based on computer vision, which makes it possible to
      recognize these beans and determine the percentage of their mixture. The
      methodology was challenged with 336 samples of National cocoa and 127 of CCN-51.
      By excluding the samples with a low fermentation level and white beans, the model
      discriminated with a precision higher than 98%. The model was also able to
      identify and quantify adulterations in 75 export batches of National cocoa and
      separate out poorly fermented beans. CONCLUSION: A scientifically reliable
      methodology able to discriminate between Ecuadorian National and CCN-51 cocoa
      beans and their mixtures was successfully developed. (c) 2017 Society of Chemical
      Industry.

PMID- 29168203
TI  - The Wisdom of Networks: A General Adaptation and Learning Mechanism of Complex
      Systems: The Network Core Triggers Fast Responses to Known Stimuli; Innovations
      Require the Slow Network Periphery and Are Encoded by Core-Remodeling.
AB  - I hypothesize that re-occurring prior experience of complex systems mobilizes a
      fast response, whose attractor is encoded by their strongly connected network
      core. In contrast, responses to novel stimuli are often slow and require the
      weakly connected network periphery. Upon repeated stimulus, peripheral network
      nodes remodel the network core that encodes the attractor of the new response.
      This "core-periphery learning" theory reviews and generalizes the heretofore
      fragmented knowledge on attractor formation by neural networks, periphery-driven
      innovation, and a number of recent reports on the adaptation of protein,
      neuronal, and social networks. The core-periphery learning theory may increase
      our understanding of signaling, memory formation, information encoding and
      decision-making processes. Moreover, the power of network periphery-related
      "wisdom of crowds" inventing creative, novel responses indicates that
      deliberative democracy is a slow yet efficient learning strategy developed as the
      success of a billion-year evolution. Also see the video abstract here:
      https://youtu.be/IIjP7zWGjVE.

PMID- 29168204
TI  - Early and medium-term outcomes of Alfieri mitral valve repair in the management
      of systolic anterior motion during septal myectomy.
AB  - BACKGROUND: This report studies the early and medium-term clinical and
      echocardiographic outcomes of the Alfieri edge-to-edge mitral valve repair, as
      adjunctive therapy, to prevent and treat systolic anterior motion (SAM) at the
      time of septal myectomy (SM) for left ventricular outflow tract obstruction in
      hypertrophic cardiomyopathy. METHODS: From 2009-2015, 11 consecutive patients had
      a trans-atrial Alfieri repair, to prevent (n = 7) or treat (n = 4) SAM at the
      time of SM. RESULTS: No patients were lost to follow-up. There were no
      perioperative or late deaths. Pre-bypass, the mean left ventricular outflow tract
      gradient, measured directly by simultaneous needle insertion, was 40.7 +/- 19.9
      mmHg at rest and 115.8 +/- 30.4 mmHg on provocation with Isoproterenol, which
      reduced after SM and Alfieri repair and discontinuation of bypass, to a mean
      gradient of 8.3 +/- 9.8 mmHg at rest and 25.8 +/- 9.2 mmHg on provocation. One
      patient who required mitral valve replacement on day 4, was hospitalized at 2.7
      years with heart failure requiring diuresis and remains well at 6 years. One
      patient developed postoperative atrial fibrillation. There were no other early or
      late complications. At a median follow-up of 6.6 years (international quartile
      range 1.2-7.4), clinical and echocardiographic data demonstrated maintained
      improvement in mean New York Heart Association class from 2.6 +/- 0.9
      preoperatively to 1.7 +/- 0.4 and reduction in mean grade of mitral regurgitation
      from 2.7 +/- 0.8 preoperatively to 0.7 +/- 0.6. CONCLUSIONS: The Alfieri repair,
      as adjunctive therapy, for the prevention or treatment of SAM at the time of SM
      demonstrates satisfactory early and medium-term clinical and echocardiographic
      outcomes supporting the ongoing utility of this approach.

PMID- 29168206
TI  - Transverse nasal crease with milia and comedones: Dermoscopic observation.

PMID- 29168205
TI  - A human microdose study of the antimalarial drug GSK3191607 in healthy
      volunteers.
AB  - AIMS: GSK3191607, a novel inhibitor of the Plasmodium falciparum ATP4 (PfATP4)
      pathway, is being considered for development in humans. However, a key problem
      encountered during the preclinical evaluation of the compound was its
      inconsistent pharmacokinetic (PK) profile across preclinical species (mouse, rat
      and dog), which prevented reliable prediction of PK parameters in humans and
      precluded a well-founded assessment of the potential for clinical development of
      the compound. Therefore, an open-label microdose (100 MUg, six subjects) first
      time in humans study was conducted to assess the human PK of GSK3191607 following
      intravenous administration of [14C]-GSK3191607. METHODS: A human microdose study
      was conducted to investigate the clinical PK of GSK3191607 and enable a Go/No Go
      decision on further progression of the compound. The PK disposition parameters
      estimated from the microdose study, combined with preclinical in vitro and in
      vivo pharmacodynamic parameters, were all used to estimate the potential efficacy
      of various oral dosing regimens in humans. RESULTS: The PK profile, based on the
      microdose data, demonstrated a half-life (~17 h) similar to other antimalarial
      compounds currently in clinical development. However, combining the microdose
      data with the pharmacodynamic data provided results that do not support further
      clinical development of the compound for a single dose cure. CONCLUSIONS: The
      information generated by this study provides a basis for predicting the expected
      oral PK profiles of GSK3191607 in man and supports decisions on the future
      clinical development of the compound.

PMID- 29168207
TI  - Abnormalities in interactions of Rho GTPases with scaffolding proteins contribute
      to neurodevelopmental disorders.
AB  - Accumulating evidence suggests that Rho GTPases, together with scaffolding SHANK
      proteins, and associated signaling pathways play a role in the development of
      autism symptoms in various conditions. Research data have brought information on
      multiple intracellular signaling pathways, including Rho-associated protein
      kinases and serine/threonine-protein kinases involved in cytoskeleton
      rearranging. Alterations in downstream effectors of GTPase signaling pathways are
      associated with neurodevelopmental disorders. Bioinformatics and experimental
      data show that complex genetic and molecular defects (GTPases, actin-binding
      proteins, kinases, neuropeptides) can result in neuronal remodeling, leading to
      the functional connectivity deficits that manifest as the heterogeneous autism
      spectrum phenotype. Finally, the known hormone and neuropeptide oxytocin appears
      to be a factor for consideration in therapeutic intervention.

PMID- 29168208
TI  - Unusual subcutaneous invasion of myxoid liposarcoma.

PMID- 29168209
TI  - Subclinical left ventricular systolic dysfunction detected by two-dimensional
      speckle tracking echocardiography in patients with pheochromocytoma and
      paraganglioma and preserved ejection fraction.
AB  - BACKGROUND: Excessive catecholamine leads to pressure overload and left
      ventricular (LV) remodeling. The goal of this study was to explore subclinical LV
      systolic dysfunction and the mechanism of preserved left ventricular ejection
      fraction (LVEF) in patients with pheochromocytoma and paraganglioma using two
      dimensional speckle tracking echocardiography. METHODS: A total of 48 patients
      with pheochromocytoma and paraganglioma and preserved LVEF and 38 age- and gender
      matched volunteers were studied. Echocardiographic parameters including LVEF, and
      global peak longitudinal and circumferential strains were measured. The
      correlation between echocardiographic parameters and blood pressure as well as
      biochemical parameters was analyzed. RESULTS: LVEF was similar between patients
      with pheochromocytoma and paraganglioma and controls. The amplitude of LV
      longitudinal strain was decreased, and the amplitude of LV circumferential strain
      was increased in the pheochromocytoma and paraganglioma group (P = .003 and P =
      .009). LV mass index and blood pressure were positively correlated with 24-hour
      urinary norepinephrine (r = .696, P < .0001; r = .470, P = .0007). The amplitude
      of LV longitudinal strain reduced with increase in blood pressure, 24-hour
      urinary norepinephrine and LV mass index (r = -.305, P = .035; r = -.506, P =
      .0002; r = -.680, P < .0001). CONCLUSIONS: This study revealed that excessive
      norepinephrine in pheochromocytoma and paraganglioma was associated with
      increased blood pressure and LV mass. The LV longitudinal strain was decreasing
      with increase in blood pressure and LV mass index. The enhanced LV
      circumferential strain might be the mechanism of compensation to maintain the
      normal LVEF in these patients.

PMID- 29168210
TI  - Abrupt generalized pustules in patients with rheumatoid arthritis and
      interstitial lung disease.
AB  - We report a case of a 30-year-old Chinese woman with rheumatoid arthritis and
      interstitial lung disease who abruptly developed generalized pustules and a high
      fever for 10 days. She had been taking oral prednisone, iguratimod and total
      glucosides of peony regularly for 5 months prior. In addition, she had taken
      metronidazole for 3 days 20 days prior which she had used before with no adverse
      reaction. She had no history of similar lesions and psoriasis. A biopsy of a
      pustule on the back showed spongiform pustule of Kogoj. She was suspected of
      having generalized pustular psoriasis or acute generalized exanthematous
      pustulosis. Finally, she was diagnosed with generalized pustular psoriasis (von
      Zumbusch type) considering the characteristics and clinical course of the rash.
      In addition to the above three drugs, systemic cyclosporin (5 mg/kg per day) was
      applied, and the lesions and fever resolved within the proceeding 2 months.

PMID- 29168211
TI  - Factors associated with medication administration errors and why nurses fail to
      report them.
AB  - BACKGROUND: Patient safety is a significant challenge facing healthcare systems.
      The administration of medication is pivotal to patient safety, and errors in drug
      administration are associated with mortality and morbidity. In this study, we
      assessed the factors contributing to the occurrence and reporting of medication
      errors from the nurse's perspective. METHODS: In this descriptive cross-sectional
      study, we distributed a validated questionnaire to 367 nurses at a large public
      hospital and obtained a response rate of 73.4%. The questionnaire comprised 65
      questions, including 29 on the causes of medication errors, 16 on the reasons why
      medication errors are not reported and 20 that estimated the percentages of the
      different medication errors actually reported. Informed consent was obtained from
      all participants, and the anonymity and confidentiality of participants'
      information were preserved throughout the process. This study received
      institutional review board approval. Descriptive statistics were used for data
      analysis. RESULTS: The main factors associated with medication errors by nurses
      were related to medication packaging, nurse-physician communication, pharmacy
      processes, nurse staffing and transcribing issues. The main barriers to the
      reporting of errors by nurses were related to the administrative response, fear
      of reporting and disagreements regarding the definitions of errors. CONCLUSION:
      Medication errors by nurses are related to medication packaging, poor
      communication, unclear medication orders, workload and staff rotation. To prevent
      medication errors, teamwork must be improved. All healthcare settings should
      emphasise awareness of the culture of safety, provide support and guidance to
      nurses and improve communication skills. We also recommend the use of integrated
      health informatics, including computerised drug administration systems. The
      limitations of this study include the potential for nonresponse bias associated
      with the sampling method. Further research is required to explore the complex and
      multidimensional causes of medication errors and review the responses of nurses
      regarding the errors reported.

PMID- 29168212
TI  - Serum 25-hydroxyvitamin D3 levels of one-month-old term infants in Tokyo using
      liquid chromatography tandem mass spectrometry.

PMID- 29168213
TI  - Economic assessment of actual prescription of drugs for treatment of atopic
      dermatitis: Differences between dermatology and pediatrics in large-scale receipt
      data.
AB  - Using large-scale receipt data, we analyzed the differences in the prescription
      of drugs and their costs between dermatology and pediatrics in the treatment of
      atopic dermatitis (AD) in children. Between August 2010 and July 2011, 50 706
      patients were diagnosed as having AD, and the data of 21 075 (15 257 dermatology,
      5818 pediatric) patients aged 0-14 years were included in this study. The use of
      classes I (strongest), II (very strong), and III (strong) topical corticosteroids
      and tacrolimus was significantly higher in dermatology than in pediatrics (class
      I, 2.88% vs 0.76%; class II, 27.68% vs 8.32%; class III, 52.53% vs 39.88%;
      tacrolimus, 5.05% vs 2.82%; all P < 0.05). Although total drug costs were higher
      in dermatology than in pediatrics, mean drug costs per person were significantly
      higher in pediatrics. Moisturizers and protective agents had the highest cost (~
      Y690 million). The introduction rate of generic drugs was low at 8.3% among
      classes I-V. The introduction rate of moisturizers and protective agents, for
      which costs were the highest, was approximately 9%. The prescription of generic
      classes II-V topical corticosteroids and moisturizers and protective agents was
      also significantly higher in dermatology than in pediatrics (P < 0.05). Among
      patients younger than 2 years, 4405 received drugs for AD; classes I and II
      topical corticosteroids and tacrolimus (against the guidelines) were
      administrated in 35 (0.8%), 474 (10.8%) and 29 patients (0.7%), respectively. The
      introduction of generic drugs is still low, and the use of generic moisturizers
      and protective agents should be addressed further.

PMID- 29168214
TI  - Transdermal light neuromodulation: Optogenetics in the murine urinary tract.
AB  - BACKGROUND: Optogenetics is a biologic technique that uses light to control
      living neurons, which have been genetically modified to express light-sensitive
      ion-channels. OBJECTIVES: Using an adenovirus to modify the sciatic nerves of
      mice, we aim to demonstrate peripheral neuromodulation of bladder pain using
      transdermal light. STUDY DESIGN: This pilot study is divided into: A)
      Confirmation and Application and B) Behavioral Step. A) Six mice were injected
      with AAV6-hSyn-ChR2(H134R)-eYFP virus into their sciatic nerves. This encoded an
      excitatory opsin, enabling light-inducible stimulation. At 4-6 weeks after
      injection, we induced foot pain responses with an activating blue 475 nm
      wavelength of light. B) Two optogenetically primed mice and two control mice
      underwent anesthesia and capsaicin was instilled into their bladders via
      catheter. The catheters were removed and the mice awoke in a chamber that exposed
      them to either blue 475 nm light or no light. Groin licking was scored in a
      binary fashion by two blinded observers. RESULTS: A) All six mice exhibited pain
      response to 475 nm blue light either by licking of foot or avoidance of light. B)
      The optogenetically primed mice had a 48% reduction in bladder pain behavior when
      exposed to blue 475 nm light whereas the control mice had a 18% reduction.
      CONCLUSION: To our knowledge this is the first demonstration of the application
      of optogenetics to modulate sensation in the lower urinary tract. It suggests
      that the process of priming peripheral nerves for optogenetic modulation is
      possible and can be used to study bladder pain response in mice.

PMID- 29168215
TI  - Non-corticosteroid adherence and itch severity influence perception of itch in
      atopic dermatitis.
AB  - Topical corticosteroid phobia is an important problem in the treatment of atopic
      dermatitis as it can affect the ability to control disease severity and itch by
      reducing treatment adherence. Topical corticosteroid phobia often ends up even
      non-corticosteroid adherence. As such, non-corticosteroid adherence, disease
      severity and itch are likely to be associated with each other, but their
      relationship has yet to be thoroughly investigated. Thus, the purpose of this
      study is to investigate it in atopic dermatitis. Using data from 1190
      participants in an Internet survey, we identified 255 non-corticosteroid users
      and 225 with moderate to severe itch who were defined as non-corticosteroid
      adherents. Corticosteroid users with the same itch categories (n = 878) served as
      controls. We also examined how itch severity affects the perception of itch in
      atopic dermatitis. Unexpectedly, non-corticosteroid adherents were less sensitive
      to the conditions to elicit itch such as perspiring, commuting homeward, drinking
      alcohol and wearing woolen clothes compared with the control. We also found that
      patients with severer itch were more sensitive to itch during/after bathing, when
      lying in bed, commuting homeward, studying/working, drinking alcohol, undressing,
      getting up in the morning, after a meal, ingesting piquant foods and when they
      were unoccupied, angry, busy, nervous, sad or enjoying themselves. In conclusion,
      we found that non-corticosteroid adherence and itch severity influence perception
      of itch in atopic dermatitis and discuss possible mechanisms underlying these
      results. The information obtained in this study may be useful for communication
      with and education of atopic dermatitis patients and their treatment in
      outpatient clinics.

PMID- 29168216
TI  - Understanding frames: A qualitative study of young people's experiences of using
      standing frames as part of postural management for cerebral palsy.
AB  - BACKGROUND: Consensus opinion supports standing frame use as part of postural
      management for nonambulant young people with cerebral palsy. Although the
      rationale for standing frame use and the associated challenges have been
      described, little attention has been given to the users' experiences. The aim of
      the current study was to explore young people's positive and negative
      experiences, and attitudes regarding standing frame use. METHODS: Framework
      analysis informed an open exploration of young people's opinions of standing
      frames. Using semistructured interviews, 12 young people with cerebral palsy (6
      female) were interviewed, providing the data set for transcription and thematic
      analysis. FINDINGS: The first theme "attitudes to standing frames" describes the
      young people's understanding of why they use standing frames. Although standing
      frames can be painful, some young people believe they should be endured to
      improve their body structure and function. There were mixed views about the
      impact standing frames have socially, with some young people feeling excluded
      from their peers, and others feeling as though standing frames helped them "fit
      in." Some young people are not offered a choice about how and when they use their
      standing frame. The second theme "challenges of standing frame use" highlights
      the issues with standing frame use such as manual handling, interference from
      siblings, and the lack of aesthetically pleasing standing frame designs.
      CONCLUSIONS: Young people report benefits related to choice, pain relief, and
      participation but can also cause pain, discomfort, and reduced independence and
      participation. Healthcare professionals should have open, informative
      conversations about potential benefits and challenges of standing frames on all
      aspects of the young people's lives, including participation and activity.

PMID- 29168217
TI  - Prevalence, management, and prognosis of bladder cancer in patients with
      neurogenic bladder: A systematic review.
AB  - AIM: To perform a systematic review of the literature regarding epidemiology,
      diagnosis, management and prognosis of bladder cancer in the neuro-urological
      patient population, in order to serve as a basis for future recommendations and
      research. METHODS: A systematic review was performed according to the PRISMA
      Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Statement.
      Embase was searched for studies providing data on epidemiology, diagnosis,
      management and prognosis of bladder cancer in neuro-urological patients. RESULTS:
      After screening 637 abstracts, 15 studies (13 retrospective and 2 prospective
      studies) were included in this study. We identified 332 patients (0.3%) who were
      diagnosed with bladder cancer. This mostly affected mostly men (59.3%) and spinal
      cord injured patients (98.8%). Mean age at diagnosis was 56.1 years. Bladder
      cancer occurred after a long period of evolution of the neurological disease
      (24.9 years). Gross hematuria was the predominating presenting symptom (31.6% of
      cases). Indwelling urethral or supra-pubic catheters were used in 44.5% of
      patients. The most frequent histological subtype of bladder cancer was
      transitional cell carcinoma (53.1%), followed by squamous cell carcinoma (33.5%).
      Muscle-invasive bladder cancer was reported in 67.7% of patients. The mean cancer
      specific mortality rate was of 47.1%. CONCLUSIONS: The prevalence and high
      mortality rate of bladder cancer in neuro-urological patients underlines the
      importance of long-term follow-up in this specific population. This highlights
      the necessity of further studies in this field.

PMID- 29168218
TI  - The clinical epidemiology of sickle cell anemia In Africa.
AB  - Sickle cell anemia (SCA) is the commonest severe monogenic disorders of humans.
      The disease has been highly characterized in high-income countries but not in sub
      Saharan Africa where SCA is most prevalent. We conducted a retrospective cohort
      study of all children 0-13 years admitted from within a defined study area to
      Kilifi County Hospital in Kenya over a five-year period. Children were genotyped
      for SCA retrospectively and incidence rates calculated with reference to
      population data. Overall, 576 of 18,873 (3.1%) admissions had SCA of whom the
      majority (399; 69.3%) were previously undiagnosed. The incidence of all-cause
      hospital admission was 57.2/100 person years of observation (PYO; 95%CI 52.6
      62.1) in children with SCA and 3.7/100 PYO (95%CI 3.7-3.8) in those without SCA
      (IRR 15.3; 95%CI 14.1-16.6). Rates were higher for the majority of syndromic
      diagnoses at all ages beyond the neonatal period, being especially high for
      severe anemia (hemoglobin <50 g/L; IRR 58.8; 95%CI 50.3-68.7), stroke (IRR 486;
      95%CI 68.4-3,450), bacteremia (IRR 23.4; 95%CI 17.4-31.4), and for bone (IRR 607;
      95%CI 284-1,300), and joint (IRR 80.9; 95%CI 18.1-362) infections. The use of an
      algorithm based on just five clinical features would have identified
      approximately half of all SCA cases among hospital-admitted children with a
      number needed to test to identify each affected patient of only fourteen. Our
      study illustrates the clinical epidemiology of SCA in a malaria-endemic
      environment without specific interventions. The targeted testing of hospital
      admitted children using the Kilifi Algorithm provides a pragmatic approach to
      early diagnosis in high-prevalence countries where newborn screening is
      unavailable.

PMID- 29168219
TI  - Waardenburg syndrome type IIE in a Japanese patient caused by a novel non-frame
      shift duplication mutation in the SOX10 gene.

PMID- 29168220
TI  - Number needed to suffer: replying to comments on my paper.

PMID- 29168221
TI  - Successful treatment of hidradenitis suppurativa with rituximab for a patient
      with idiopathic carpotarsal osteolysis and chronic active antibody-mediated
      rejection.

PMID- 29168222
TI  - The prognostic significance of frailty compared to peak oxygen consumption and B
      type natriuretic peptide in patients with advanced heart failure.
AB  - Frailty assessment has become an integral part of the evaluation of potential
      candidates for heart transplantation and ventricular assist device (HTx/VAD). The
      impact of frailty, as a heart failure risk factor or to identify those who will
      derive the greatest benefit with HTx/VAD remains unclear. The aim of this study
      was to evaluate the independent prognostic relevance of frailty assessment from
      peak oxygen consumption (peak VO2 ) or B-type natriuretic peptide (BNP) on
      mortality in patients referred for advanced heart failure therapies. Frailty was
      measured using modified Fried frailty criteria. In 201 consecutive patients,
      during a median follow-up of 17.5 months (IQR 11-29.2), there were 25 (12.4%)
      deaths. One-year survival was 100%, 94%, and 78% in nonfrail, prefrail, and frail
      patients, respectively (log rank P = .0001). Frailty was associated with a
      twofold increase risk of death (HR 2.01, P < .0001, 95% CI 1.42-2.84). When
      adjusted for BNP or peak VO2 , frailty was not associated with a significant risk
      of all-cause death. However, when peak VO2 is stratified into two categories
      (>=12 mL/kg/min vs <12 mL/kg/min), frailty was associated with increased
      mortality in patients with a lower peak VO2 (HR 1.72, P = .006).

PMID- 29168223
TI  - Agranulocytosis associated with voriconazole-induced hypersensitivity syndrome.

PMID- 29168224
TI  - Dynamics in the global protected-area estate since 2004.
AB  - Nations of the world have committed to a number of goals and targets to address
      global environmental challenges. Protected areas have for centuries been a key
      strategy in conservation and play a major role in addressing current challenges.
      The most important tool used to track progress on protected-area commitments is
      the World Database on Protected Areas (WDPA). Periodic assessments of the world's
      protected-area estate show steady growth over the last 2 decades. However, the
      current method, which uses the latest version of the WDPA, does not show the true
      dynamic nature of protected areas over time and does not provide information on
      sites removed from the WDPA. In reality, this method can only show growth or
      remain stable. We used GIS tools in an approach to assess protected-area change
      over time based on 12 temporally distinct versions of the WDPA that quantify area
      added and removed from the WDPA annually from 2004 to 2016. Both the narrative of
      continual growth of protected area and the counter-narrative of protected area
      removal were overly simplistic. The former because growth was almost entirely in
      the marine realm and the latter because some areas removed were reprotected in
      later years. On average 2.5 million km2 was added to the WDPA annually and 1.1
      million km2 was removed. Reasons for the inclusion and removal of protected areas
      in the WDPA database were in part due to data-quality issues but also to on-the
      ground changes. To meet the 17% protected-area component of Aichi Biodiversity
      Target 11 by 2020, which stood at 14.7% in 2016, either the rate of protected
      area removal must decrease or the rate of protected-area designation and addition
      to the WDPA must increase.

PMID- 29168225
TI  - GABA-modulating phytomedicines for anxiety: A systematic review of preclinical
      and clinical evidence.
AB  - Anxiety disorders are chronic and functionally disabling conditions with high
      psychological stress, characterised by cognitive symptoms of excessive worry and
      focus difficulties and physiological symptoms such as muscle tension and
      insomnia. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter within
      the central nervous system and is a key target of pharmacotherapies in the
      treatment of anxiety. Although current pharmaceutical treatments are often
      efficacious, they may cause undesirable side effects including cognitive
      decrements and withdrawal symptoms. Plant-based "phytomedicines" may provide
      novel treatment options, to act as an adjunctive or alternative to existing
      anxiolytic medications. As such, we conducted a systematic review to assess the
      current body of literature on anxiolytic phytomedicines and/or phytoconstituents.
      An open-ended search to 5 July 2017 was conducted using MEDLINE (PubMed), Scopus,
      and Cochrane library online databases and performed in a stepped format from
      preclinical to clinical investigations. Eligible studies must have had (a) in
      vitro evidence of GABA-modulating activity, (b) animal studies using anxiety
      models to test an anxiolytic effect, and (c) human clinical trials. Ten
      phytomedicines were identified as having preclinical investigations showing
      interaction with the GABA system, in addition to human clinical trials: kava,
      valerian, pennywort, hops, chamomile, Ginkgo biloba, passionflower, ashwagandha,
      skullcap, and lemon balm. Collectively, the literature reveals preclinical and
      clinical evidence for various phytomedicines modulating GABA-pathways, with
      comparative anxiolytic effect to the current array of pharmaceuticals, along with
      good safety and tolerability profiles.

PMID- 29168226
TI  - Three cases of Nagashima-type palmoplantar keratosis associated with atopic
      dermatitis: A diagnostic pitfall.

PMID- 29168227
TI  - Alternatives to biodiversity offsets for mitigating the effects of urbanization
      on stream ecosystems.
AB  - Globally, offset schemes have emerged in many statutory frameworks relating to
      development activities, with the aim of balancing biodiversity conservation and
      development. Although the theory and use of biodiversity offsets in terrestrial
      environments is broadly documented, little attention has been paid to offsets in
      stream ecosystems. Here we examine the application of offset schemes to stream
      ecosystems and explore whether they suffer similar shortcomings to those of
      offset schemes focused on terrestrial biodiversity. To challenge the
      applicability of offsets further, we discuss typical trajectories of urban
      expansion and their cascading physical, chemical and biological impacts on stream
      ecosystems. We argue that the highly connected nature of stream ecosystems and
      urban drainage networks can transfer impacts of urbanization across wide areas,
      complicating the notion of like-for-like exchange and the prospect of effectively
      mitigating biodiversity loss. Instead, we identify in-catchment options for
      stormwater control, which can avoid or minimize the impacts of development on
      downstream ecosystems, while presenting additional public and private benefits.
      We describe the underlying principles of these alternatives, some of the
      challenges associated with their uptake, and policy initiatives being trialed to
      facilitate adoption. In conclusion, we argue that stronger policies to avoid and
      minimize the impacts of urbanization provide better prospects for protecting
      downstream ecosystems, and can additionally, stimulate economic opportunities and
      improve urban liveability.

PMID- 29168228
TI  - Trajectory of spirometric and exhaled nitric oxide measurements in Chinese
      schoolchildren with asthma.
AB  - BACKGROUND: Lung function growth occurs in most asthmatic children. A subgroup
      has subnormal lung function trajectory, but such data are limited in children.
      This prospective study characterized longitudinal changes of spirometric indices
      and fractional exhaled nitric oxide level (FeNO) among asthmatic children and
      identified their genetic and environmental determinants. METHODS: Chinese
      asthmatic children recruited from pediatric clinics underwent 5-year follow-up
      for pre-bronchodilator spirometric indices and FeNO. Fourteen asthma-associated
      single nucleotide polymorphisms (SNPs) were genotyped. Generalized estimating
      equation was used to analyze longitudinal changes of spirometric indices and
      FeNO. RESULTS: One hundred and ninety-three asthmatic children, aged 9.7 (1.9)
      years, had significant annual decline of 1.3% for forced vital capacity (FVC) and
      annual increase of 1.2% and 3.6% for FEV1 /FVC and FEF25-75 , respectively.
      Patients who received inhaled corticosteroid (ICS) had 2.4% lower baseline FEV1
      /FVC but 0.81% higher annual increase in FEV1 . Body mass index (BMI) was
      associated inversely with FEV1 /FVC but positively with FEV1 % and FVC% changes.
      Asthma exacerbation was associated with lower FEV1 % and FVC% but not their
      longitudinal changes. When classified by FEV1 curve, one-quarter of patients had
      reduced lung function growth which was associated with female gender and lower
      spirometric and higher FeNO values at baseline. IL33_rs1342326 was associated
      with spirometric indices and FeNO, whereas GSDMB_rs2305480 was significantly
      associated with FEV1 /FVC change. CONCLUSION: Asthmatic children have annual
      decline in FVC and increase in FEV1 /FVC and FEF25-75 . Their lung function
      trajectory is influenced by gender, ICS treatment, BMI, and asthma exacerbations.
      IL33 and GSDMB may be candidate genes for their lung function growth.

PMID- 29168229
TI  - Visualization of the bone marrow biopsy needle track.

PMID- 29168230
TI  - Routine guidewire application facilitates cholangioscopy in the management of
      postoperative residual hepatolithiasis.
AB  - BACKGROUND AND AIM: Although postoperative cholangioscopy (POC) is considered to
      be an effective treatment for residual hepatolithiasis after surgery, its
      security and validity still need to be improved. This study compared wire-guided
      POC (WG-POC) versus traditional POC (T-POC) in the management of patients with
      residual hepatolithiasis. METHODS: This retrospective study included a total of
      203 patients who suffered from hepatolithiasis and underwent hepatectomy as
      initial intervention from 1 January 2016 to 1 January 2017. After surgery, 110
      patients were subjected to T-POC and 93 to WG-POC for eliminating residual
      hepatolithiasis. Perioperative course and follow-up outcomes were retrospectively
      analyzed. RESULTS: No significant differences in clinical characteristics or
      distribution of residual hepatolithiasis between the WG-POC and T-POC groups were
      observed (P > 0.05). However, overall POC interventional sessions (2.9 +/- 0.85
      vs 4.0 +/- 1.21 times), average operating time (264.8 +/- 103.61 vs 389.4 +/-
      136.26 min), overall complications rate (18.28% vs 32.73%), and overall T-tube
      retaining time (21.8 +/- 6.20 vs 28.8 +/- 8.09 days) were lower in the WG-POC
      group than in the T-POC group (P < 0.05). In addition, there were no significant
      differences between the two groups (WG-POC vs T-POC) in recurrence (4.30% vs
      4.55%) and residual calculi (8.60% vs 6.36%) at half-a-year follow up (P > 0.05).
      CONCLUSIONS: Routine wire guidance may improve the outcome of cholangioscopy in
      managing complicated residual hepatolithiasis, being associated with clear
      advantages such as shorter operating time and number of POC interventions,
      reduced T-tube retaining time, and fewer postoperative complications.

PMID- 29168231
TI  - A new hybrid anchoring balloon for direct peroral cholangioscopy using an
      ultraslim upper endoscope.
AB  - BACKGROUND AND AIM: Large impacted or residual invisible common bile duct (CBD)
      stones after mechanical lithotripsy are challenging. We aimed to evaluate the
      feasibility and success rate of a new hybrid anchoring balloon-guided direct
      peroral cholangioscopy (POC) for these conditions using an ultraslim endoscope.
      METHODS: Sixty-five patients with large or residual invisible CBD stones for
      direct POC from July 2012 to July 2016 were identified, including six cases in
      whom an additional interventional procedure was required. There were altogether
      55 cases undergoing a procedure with our new device, with a 0.021-inch guidewire
      tied to a balloon catheter at its distal end in this single-center retrospective
      study. Technical success, procedure time, diagnostic and therapeutic efficacy of
      direct POC, and procedure-related complications were studied. RESULTS: The hybrid
      anchoring balloon-guided direct POC was successful in 51/55 (92.7%) procedures,
      including 18 cases in whom the conventional wire-guided method failed within 25
      min. Mean time for technical success by our method was 12.4 +/- 3.4 min. In
      total, of the 43 cases with previous removal of CBD stones, seven (16.3%) were
      found to have residual stones >=4 mm, excluding three cases in whom direct POC
      failed. In another 25 cases for difficult stones, 24 lithotripsies were carried
      out, resulting in 23 complete fragmentations. No significant procedure-related
      complications were observed. CONCLUSION: The new hybrid anchoring balloon device
      performs well in facilitating direct POC using an ultraslim endoscope for
      evaluation and extraction of residual or large impacted CBD stones.

PMID- 29168233
TI  - Progression to invasive cancer from sessile serrated adenoma/polyp.

PMID- 29168232
TI  - Current state and future of pediatric allergology in Europe: A road map.
AB  - The history of pediatric allergology (PA) in Europe is relatively youthful,
      dating back to 1984, when a small group of pediatricians founded the European
      Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI
      (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the
      first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded.
      There are striking differences across Europe, and even within European countries,
      in relation to the training pathways for doctors seeing children with allergic
      disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and
      sponsored a workshop with the European Academy of Allergy and Clinical Immunology
      (EAACI) Pediatric Section. This collaboration focussed on the future of PA and
      specifically on education, research, and networking/ advocacy. The delegates
      representing many countries across Europe have endorsed the concept that optimal
      care of children with allergic diseases is delivered by pediatricians who have
      received dedicated training in allergy, or allergists who have received dedicated
      training in pediatrics. In order to meet the needs of children and families with
      allergic disease(s), the pediatric allergist is highly encouraged to develop
      several networks. Our challenge is to reinforce a clear strategic approach to
      scientific excellence to across our member base and to ensure and enhance the
      relevance of European pediatric research in allergy. With research opportunities
      in basic, translational, clinical, and epidemiologic trials, more trainees and
      trained specialists are needed and it is an exciting time to be a pediatric
      allergologist.

PMID- 29168234
TI  - Impact of comorbidities constituting the hematopoietic cell transplant (HCT)
      comorbidity index on the outcome of patients undergoing allogeneic HCT for acute
      myeloid leukemia.
AB  - OBJECTIVE: To investigate the prognostic impact of the individual component
      comorbidities of the hematopoietic cell transplant comorbidity index (HCT-CI) in
      patients with acute myeloid leukemia (AML) that underwent allogeneic
      hematopoietic cell transplant (HCT). METHOD: This single-center study
      retrospectively investigated the individual comorbidities of the HCT-CI on the
      outcome of 418 patients that underwent HCT for AML, in CR1 (n = 303, 72%) or CR2
      (n = 115, 28%) at our center between 1999 and 2014. RESULTS: Median age at HCT
      was 50 years (range 18-71). Univariate analysis of the HCT-CI, grouped as score 0
      (n = 109), 1-2 (n = 157) and >=3 (n = 152), demonstrated significant influence on
      overall survival (OS) (P = .004) and non-relapse mortality (NRM) (P = .02). For
      individual comorbidities constituting the HCT-CI, variables with a P-value <= .2
      on univariate analysis were included in the multivariable analysis. For OS, none
      of the comorbidities of the HCT-CI demonstrated independent prognostic relevance.
      However, for NRM, multivariable analysis demonstrated pretransplant diabetes (HR
      = 2.17, 95% CI = 1.31-3.60, P = .003) and cardiovascular comorbidity (HR = 1.78,
      95% CI = 1.15-2.76, P = .01) to be independent predictors of NRM post-transplant.
      CONCLUSION: Among the comorbidities that compose the HCT-CI, diabetes and
      cardiovascular comorbidity independently predict NRM in patients undergoing
      allogeneic HCT for AML. This information should be taken into consideration
      regarding post-transplant monitoring and care.

PMID- 29168235
TI  - Effects of nutraceuticals on sexual satisfaction and lower urinary tract symptoms
      in a cohort of young-old men.
AB  - The aim of this study was to evaluate the effects of nutraceuticals containing
      multiple supplemental facts (Virherbe(r)/Rekupros(r)) on sexual satisfaction and
      lower urinary tract symptoms (LUTS) in young-old men. In an open-label trial, 40
      males (mean age 66 +/- 13) with sexual disturbances and mild LUTS but without
      cognitive/motor impairment and clinical hypogonadism were enrolled. Sexual desire
      (SD; IIEF-SD domain) and satisfaction (Global Assessment Question; GAQ), the
      capacity to perform daily activities (evaluated by 6-min walking test [6MWT]),
      and International Prostate Symptoms Scores (IPSS) were evaluated before and after
      oral administration of 2 capsules/day of each supplement for 8 weeks. The
      difference from baseline for SD was +2.6 (p < .05) and -4.2 points for IPSS (p <
      .05), with significance in subscales of urinary streaming/nocturia (p < .01),
      respectively; 6MWT increased from 507 +/- 44 versus 527 +/- 58 meters (p < .001).
      GAQ scale-responses showed overall improvement in overall 75% population, with a
      significant improvement in QoL (p < .01). These changes returned to baseline at 1
      month withdrawal follow-up. No adverse events were reported. These supplemental
      facts improved sexual desire, satisfaction with sex life, physical performance,
      and LUTS in young-old men, suggesting that they may be effective in patients in
      whom standard treatments are not suitable.

PMID- 29168237
TI  - Short high-power RF application.

PMID- 29168236
TI  - A prospective multicenter phase II study of intrabone marrow transplantation of
      unwashed cord blood using reduced-intensity conditioning.
AB  - Cord blood transplantation (CBT) is associated with delayed hematopoietic
      recovery and graft failure. To overcome these problems, we conducted a
      prospective, multicenter phase II study of intrabone marrow transplantation in
      which patients received reduced-intensity conditioning without anti-thymocyte
      globulin (ATG). The primary endpoint was the probability of full donor
      engraftment. Forty patients with hematologic malignancies were enrolled. Cord
      blood (CB) cells were injected without washing into 4 iliac bone sites (2 at each
      hemipelvis), at which approximately 6 mL of CB was administered at one site with
      local anesthesia. Full donor engraftment rate was 86.8%. The cumulative incidence
      of neutrophil and platelet engraftment was 86.4% and 85.5%, respectively. The
      median time to neutrophil (>0.5 * 109 /L) and platelet (2.0 * 109 /L) recovery
      was 17.5 and 44 days, respectively. The probability of severe acute graft-vs-host
      disease (GVHD) was 47.5%. The cumulative incidence of extensive chronic GVHD was
      3.0%. The probability of relapse and non-relapse mortality was 30.4% and 28.0%,
      respectively. The survival rate at 3 years was 45.6%, although most patients were
      at an advanced stage. These results suggest that our intrabone marrow-CBT
      procedure without using ATG improves hematopoietic recovery and decreases the
      incidence of chronic GVHD, but does not decrease the incidence of acute GVHD.

PMID- 29168238
TI  - Xenotransplantation literature update, September/October 2017.

PMID- 29168239
TI  - Evaluation of a diagnostic therapeutic educational pathway for asthma management
      in youth.
AB  - BACKGROUND: In spite of some evidence for positive effects of patient's education
      to asthma self-management by randomized clinical trials, there are few studies on
      the impact of patient' s educational programs in the real world. We aimed to
      assess the impact of a diagnostic therapeutic educational pathway (DTEP) on
      asthma control of children and adolescents by comparing frequency of outcomes
      indicative of asthma control before and after attending the pathway. METHODS:
      This is a retrospective cohort study including all patients aged 6-11 and 12-17
      years who attended the DTEP in 2007-2014. The DTEP includes 3 specialist's
      evaluations at 8- to 12-week intervals and two follow-up visits. Patients and
      their parents receive an educational course concerning prevention measures, early
      recognition of symptoms, and appropriate use of drugs and devices. The rates of
      hospitalizations, outpatient services, emergency room visits, and drug
      prescriptions were considered as outcomes and computed as number of events
      divided by person-time. RESULTS: A total of 806 patients were enrolled. A
      statistically significant decrease in rates from before to after DTEP was
      observed for almost all outcomes, in both age groups, with relative risks ranging
      from 0.12 to 0.60. The rates of drug prescription showed a statistically
      significant decrease, from before to after DTEP, for each type of medicine for
      asthma, in both age groups, from percent difference of -66% to -24.3%.
      CONCLUSIONS: The positive impact of this program on the outcomes indicative of
      asthma control in both children and adolescents suggests that it may be valuable
      for asthma management.

PMID- 29168240
TI  - Citrus essential oils inhalation by mice: Behavioral testing, GCMS plasma
      analysis, corticosterone, and melatonin levels evaluation.
AB  - The use of orange essential oils (EOs) as a complementary treatment is very
      common in Brazilian popular culture. The levels of melatonin (MEL) and
      corticosterone (CORT) hormones were investigated simultaneously, by the LuminexTM
      immunoassay system in mice plasma, after Citrus aurantium and Citrus sinensis EOs
      inhalation for 30 min. The plasma was analyzed by headspace through gas
      chromatography coupled to mass spectrometry for investigation of the EO
      components. Mice were submitted to behavioral testing to research anxiolytic
      like, sedative, and antidepressant-like effects. The inhalation of atmosphere
      obtained from vaporization of 10% solution of this Citrus EO separately did not
      affect MEL or CORT plasma levels; that is, the MEL and CORT levels did not
      present variation in function of the EO in the schedule used. On the other hand,
      the imipramine positive control used altered the level of MEL as expected. The EO
      constituents were detected in plasma at different ratios that is present in
      inhaled EO. Behavioral tests showed that the inhalation of 10% C. sinensis EO
      presents an anxiolytic-like and sedative effect. Thus, C. sinensis EO can be a
      valuable tool for treatment of the anxiety disturbs, apparently without
      interference with MEL and CORT physiological levels.

PMID- 29168241
TI  - Can a child and family health service improve early childhood health outcomes in
      an urban Aboriginal community?
AB  - AIMS: To describe the engagement of a cohort of urban Aboriginal families with an
      Early Childhood Health Service, and to assess any association of engagement with
      the service with screening by the Edinburgh Post-Natal Depression Scale (EPDS),
      full breastfeeding rates and post-natal smoking status. METHODS: Routine
      electronic medical record data collected by a Child and Family Health Nurse
      between 2011 and 2014 was analysed retrospectively. Associations between use of
      the service and acceptance of EPDS, breastfeeding rates and post-natal smoking
      status were determined using binary and multinomial multiple logistic regression
      analyses. RESULTS: There were 424 Aboriginal babies and 215 mothers included in
      the study. Each occasion of service increased the odds of accepting screening
      with the EPDS (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.00-1.03, P =
      0.04) and complete breastfeeding (OR 1.11, CI 1.01-1.23, P = 0.04), but not of
      quitting smoking (OR 0.99, CI 0.96-1.02, P = 0.34). Despite accounting for
      engagement with the service, overall uptake of the EPDS remained low; of 267
      offers for EPDS screening, only 115 were accepted (43%). CONCLUSION: The service
      was accessed in increasing numbers during the study period. Mothers who utilised
      the service more frequently were more likely to accept EPDS screening and
      exclusively breastfeed; however, acceptance of EPDS screening remained low
      overall. Further research is recommended to investigate the low acceptance of
      EPDS in this Aboriginal population and whether those results are transferable to
      other communities.

PMID- 29168242
TI  - Compositional differences between Copaxone and Glatopa are reflected in altered
      immunomodulation ex vivo in a mouse model.
AB  - Copaxone (glatiramer acetate, GA), a structurally and compositionally complex
      polypeptide nonbiological drug, is an effective treatment for multiple sclerosis,
      with a well-established favorable safety profile. The short antigenic polypeptide
      sequences comprising therapeutically active epitopes in GA cannot be deciphered
      with state-of-the-art methods; and GA has no measurable pharmacokinetic profile
      and no validated pharmacodynamic markers. The study reported herein describes the
      use of orthogonal standard and high-resolution physicochemical and biological
      tests to characterize GA and a U.S. Food and Drug Administration-approved generic
      version of GA, Glatopa (USA-FoGA). While similarities were observed with low
      resolution or destructive tests, differences between GA and USA-FoGA were
      measured with high-resolution methods applied to an intact mixture, including
      variations in surface charge and a unique, high-molecular-weight, hydrophobic
      polypeptide population observed only in some USA-FoGA lots. Consistent with
      published reports that modifications in physicochemical attributes alter immune
      related processes, genome-wide expression profiles of ex vivo activated
      splenocytes from mice immunized with either GA or USA-FoGA showed that 7-11% of
      modulated genes were differentially expressed and enriched for immune-related
      pathways. Thus, differences between USA-FoGA and GA may include variations in
      antigenic epitopes that differentially activate immune responses. We propose that
      the assays reported herein should be considered during the regulatory assessment
      process for nonbiological complex drugs such as GA.

PMID- 29168243
TI  - Iron sucrose: assessing the similarity between the originator drug and its
      intended copies.
AB  - Iron sucrose (IS) is a complex nanocolloidal intravenous suspension used in the
      treatment of iron-deficiency anemia. Follow-on IS products (iron sucrose similars
      (ISSs)) have obtained marketing authorization by the generic pathway, implying
      that identical copies of IS may be manufactured. However, recent prospective and
      retrospective clinical studies showed discrepancies in clinical outcomes, which
      might be related to differences in physicochemical properties. The aim of this
      work is to measure and compare the physicochemical properties of IS and three
      ISSs available in the market using innovative analytical procedures. The
      comprehensive elucidation of size, size distribution, morphology, and stability
      of these complex drugs revealed very significant differences between the
      products. This study serves to provide the basis to define critical quality
      attributes that may be linked to differences in clinical outcome and thus may
      contribute to an adequate regulatory approach for IS and its follow-on products.

PMID- 29168244
TI  - Using preceding hospital admissions to identify children at risk of developing
      acute rheumatic fever.
AB  - AIMS: New Zealand (NZ) Maori and Pacific children have high rates of acute
      rheumatic fever (ARF). Around 150 new cases arise each year. As part of the
      national ARF prevention programme, funding is available to improve housing. To
      obtain maximum benefit from interventions, an effective tool is needed for
      targeting high-risk children. This study aimed to assess the effectiveness of
      using hospitalisations for identifying children at risk of subsequent ARF.
      METHODS: Three potentially avoidable hospitalisation (PAH) groups were
      investigated, including diseases thought to be influenced by housing. All were
      developed using expert opinion or systematic reviews. These were: (i) the PAH
      conditions associated with the housing environment (PAHHE) group; (ii) the
      Crowding group; and (iii) the Ministry of Health (MoH) group. We analysed NZ
      public hospital discharge data (2000-2014). The prevalence of ARF among patients
      hospitalised in each group was calculated to estimate sensitivity and potential
      effectiveness. The number needed to screen (NNS) to identify one ARF case was
      estimated as a measure of efficiency. RESULTS: Nearly one-third of ARF patients
      experienced a PAH as children (before developing ARF). Sensitivity for detecting
      future ARF ranged from <5% (MoH group) to 27% (PAHHE group). NNS ranged from
      502.4 (PAHHE) to 707.5 (MoH). CONCLUSIONS: Because ARF is relatively rare,
      observing hospitalisations is not particularly efficient for targeting prevention
      activities for this condition alone. However, housing interventions are likely to
      improve multiple outcomes; thus, the hospital setting is still useful for
      identifying at-risk children who could benefit from such programmes.

PMID- 29168245
TI  - Homology-based hydrogen bond information improves crystallographic structures in
      the PDB.
AB  - The Protein Data Bank (PDB) is the global archive for structural information on
      macromolecules, and a popular resource for researchers, teachers, and students,
      amassing more than one million unique users each year. Crystallographic structure
      models in the PDB (more than 100,000 entries) are optimized against the crystal
      diffraction data and geometrical restraints. This process of crystallographic
      refinement typically ignored hydrogen bond (H-bond) distances as a source of
      information. However, H-bond restraints can improve structures at low resolution
      where diffraction data are limited. To improve low-resolution structure
      refinement, we present methods for deriving H-bond information either globally
      from well-refined high-resolution structures from the PDB-REDO databank, or
      specifically from on-the-fly constructed sets of homologous high-resolution
      structures. Refinement incorporating HOmology DErived Restraints (HODER),
      improves geometrical quality and the fit to the diffraction data for many low
      resolution structures. To make these improvements readily available to the
      general public, we applied our new algorithms to all crystallographic structures
      in the PDB: using massively parallel computing, we constructed a new instance of
      the PDB-REDO databank (https://pdb-redo.eu). This resource is useful for
      researchers to gain insight on individual structures, on specific protein
      families (as we demonstrate with examples), and on general features of protein
      structure using data mining approaches on a uniformly treated dataset.

PMID- 29168247
TI  - Weak D type 1, 2 and 3 subtype alleles are rare in the Western French population.

PMID- 29168246
TI  - Immunostimulatory effects of cordycepin-enriched WIB-801CE from Cordyceps
      militaris in splenocytes and cyclophosphamide-induced immunosuppressed mice.
AB  - The medicinal mushroom Cordyceps militaris has been reported to possess
      anticancer and immunomodulatory effects. We investigated the immunostimulatory
      effects of culture supernatant of C. militaris (WIB-801CE) by examining its in
      vitro enhancing effects on cell proliferation and cytokine releases in
      splenocytes and its in vivo effects on cyclophosphamide-induced immunosuppressed
      mice. WIB-801CE enhanced normal and methotrexate-induced cell proliferation. WIB
      801CE significantly ameliorated interleukin (IL)-2, interferon-gamma, and tumor
      necrosis factor-alpha secretion in methotrexate-induced splenocytes. Oral
      administration of WIB-801CE effectively increased the cyclophosphamide-suppressed
      splenocyte proliferation and natural killer cytotoxic activity. WIB-801CE
      effectively recovered cyclophosphamide-induced decreases in IL-2, interferon
      gamma, tumor necrosis factor-alpha, and IL-10 level. The collective data
      implicate WIB-801CE as a therapeutic candidate in ameliorating the
      immunosuppression through immunostimulatory properties.

PMID- 29168248
TI  - Evaluation of C-reactive protein as an inflammatory marker of pemphigus foliaceus
      and superficial pyoderma in dogs.
AB  - BACKGROUND: C-reactive protein (CRP) is a major acute phase protein in dogs and
      may be an inflammatory marker of autoimmune diseases. HYPOTHESIS/OBJECTIVES: To
      measure pre- and post-treatment CRP levels in dogs with superficial pyoderma (SP)
      and pemphigus foliaceus (PF) compared to normal dogs; to evaluate possible
      correlation between CRP values, indirect immunofluorescence (IIF), and pemphigus
      foliaceus extent and severity index (PEFESI) scores. ANIMALS: Fifty nine dogs
      divided into three groups: Group I (control, n = 31), Group II (SP, n = 14) and
      Group III (PF, n = 14). METHODS: CRP levels were measured in Group I dogs. Skin
      biopsies of Groups II and III dogs were obtained for histopathological
      examination. In Group II dogs, CRP levels were measured at days 0, 15, 30 and 60.
      In Group III dogs were evaluated by PEFESI, IIF and CRP levels at days 0, 15, 30,
      60 and 90. RESULTS: Group III showed a higher median CRP (37.4 mg/mL) compared to
      the other groups (Group I, CRP 2.9 mg/mL, P < 0.0001; Group II CRP 3.8 mg/mL, P =
      0.008). There was no significant difference in CRP levels between groups I and
      II. IIF titres and CRP levels decreased in most cases of PF with clinical
      improvement. Dogs with CRP >10.6 MUg/mL were 5.5 times more likely to have PF
      than SP. There was a strong positive correlation between CRP values and PEFESI
      and a weak positive correlation between CRP values and IIF titres. CONCLUSION AND
      CLINICAL IMPORTANCE: CRP levels are increased in dogs with PF and exceed levels
      found in most dogs with SP.

PMID- 29168249
TI  - Violent crime redistribution in a city following a substantial increase in the
      number of off-sale alcohol outlets: A Bayesian analysis.
AB  - INTRODUCTION AND AIMS: This study examined whether the introduction of a large
      number of off-premise alcohol outlets into a city over a brief period of time
      could affect rates of violent crime. DESIGN AND METHODS: The study analysed
      annual counts of violent crime across 172 US Census block groups in Lubbock,
      Texas from 2006 through 2011. Spatial Poisson models related annual violent crime
      counts within each block group to off-premise and on-premise alcohol outlets
      active during this time period as well as neighbourhood socio-demographic
      characteristics. The effects of alcohol outlets were assessed both within block
      groups and across adjacent block groups. RESULTS: On-premise outlets had a small,
      significant positive association with violence within a given block group. A
      similar well-supported local effect for off-premise outlets was not found.
      However, the spatially lagged effect for off-sale premises was well-supported,
      indicating that greater densities of these outlets were related to greater rates
      of violent crime in adjacent areas. DISCUSSION AND CONCLUSIONS: While these
      analyses confirmed a previous time-series analysis in finding no city-wide effect
      of the increase in off-premise outlets, they do suggest that such outlets in a
      local area may be related to violence in nearby geographic areas. They indicate
      the importance of examining neighbourhood-specific effects of alcohol outlets on
      violence in addition to the city-wide effects. They also present further evidence
      supporting the need to examine the differential effects of on-sale and off-sale
      premises.

PMID- 29168250
TI  - The effect of skin-to-skin care on cerebral oxygenation during nasogastric
      feeding of preterm infants.
AB  - AIM: To describe cerebral oxygenation during gavage feeding of preterm infants
      during incubator and skin-to-skin care. METHODS: Further analysis of data from
      two crossover studies comparing cerebral oxygenation, heart rate and oxygen
      saturation during skin-to-skin care with incubator care. Data were analysed in
      three epochs; 10 minutes prefeed, during-feed and 10 minutes postfeed.
      Measurements from infants fed during incubator care were compared with those
      obtained during skin-to-skin care. RESULTS: In 39 infants [median (IQR) 27.8
      (26.1-30.0) weeks' gestation], there was no difference in cerebral oxygenation
      between pre-, during- and postfeed. Heart rate increased by three beats per
      minute postfeed compared with during-feed. Twenty infants received two gavage
      feeds, one feed in the incubator and another during skin-to-skin care. There was
      no difference in cerebral oxygenation and heart rate; peripheral oxygen
      saturation decreased by 3% during feeding whilst skin-to-skin care compared with
      feeding in the incubator. CONCLUSION: Cerebral oxygenation remained stable
      before, during and after gavage feeding in an incubator and during skin-to-skin
      care. The small decrease in oxygen saturation whilst receiving gavage feeding
      during skin-to-skin care is unlikely to be clinically important, providing
      reassurance that preterm infants maintain physiological stability during skin-to
      skin care.

PMID- 29168251
TI  - Bendamustine plus rituximab for indolent B-cell lymphoma of renal significance.
AB  - Treatment of indolent B-cell non-Hodgkin lymphomas (iNHL) of renal significance
      is challenging given the need for deep and prolonged hematological response to
      restore and control renal function overtime, yet to be balanced with the risk of
      adverse drug-related events. This prospective single-center study included 20
      patients with iNHL of renal significance (tubulointerstitial presentation [n =
      8], glomerulopathy with or without monoclonal Ig deposits [n = 12]) who received
      a steroid-sparing regimen of rituximab plus bendamustine (BR), with either no or
      <1 month of steroid intake (as a first line therapy in 80%). Seventeen patients
      (85%) achieved a complete (CHR, n = 12) or a partial (PHR, n = 5) hematological
      response. Nine out of the 12 patients (75%) with iNHL-related glomerulopathy had
      a complete (CRR) or a partial (PRR) renal response. Among the six patients with
      glomerulopathy and CHR, five had a CRR (83%) compared to 1/6 (17%) that did not
      reach CHR. eGFR increased from 38 to 58 mL/min/1.73 m2 , and returned to baseline
      in five patients. Among the eight patients with a tubulointerstitial
      presentation, six (75%) had a renal response (5 CRR), and eGFR increased from 29
      to 48 mL/min/1.73 m2 . One patient with a PHR had a renal relapse. Mortality rate
      was 10% at 12 months. The BR regimen was well tolerated overall. Thus, despite
      severe renal disease at presentation, a relapsing iNHL in 20% of patients and
      several comorbidities, the BR regimen was efficient and safe in our series. It
      should be further assessed as a first line therapy for patients with iNHL of
      renal significance.

PMID- 29168254
TI  - Ethanol Iris tenuifolia extract reduces brain damage in a mouse model of cerebral
      ischaemia.
AB  - In the previous experiments, the neuroprotective role of Iris tenuifolia Pall.
      (IT) in the model of middle cerebral artery occlusion (MCAO) was investigated. In
      addition, the concentrations of the cytokines tumour necrosis factor-alpha and
      interleukin-6 in blood plasma were measured. It was found that IT administered 1
      hr prior to MCAO or immediately after MCAO reduced infarct volume significantly.
      IT application 1 and 4 hr after MCAO, respectively, was without any effect on
      infarct volume. There were no significant changes as regards tumour necrosis
      factor-alpha, whereas interleukin-6 concentrations were increased in blood
      plasma. This is the first evidence that flavonoids from Iris tenuifolia exert
      protective effects in the in vivo MCAO model. Our results suggest that these
      flavonoids are likely to be beneficial to humans by virtue of their ability to
      reduce infarct volume.

PMID- 29168255
TI  - Nasal cytology: a Precision Medicine tool in clinical practice.

PMID- 29168253
TI  - Genomewide association study of HLA alloimmunization in previously pregnant blood
      donors.
AB  - BACKGROUND: Alloimmunization through blood transfusion, transplantation, or
      circulating fetal cells during pregnancy is a significant concern. Some exposed
      individuals make alloantibodies while others do not, implying variation in
      genetic risk factors. STUDY DESIGN AND METHODS: We conducted a genomewide
      association study (GWAS) of 9,427,497 single-nucleotide polymorphisms (SNPs) to
      identify genetic variants for HLA alloimmunization in previously pregnant blood
      donors with (n = 752) and without (n = 753) HLA Class I or II alloantibodies.
      RESULTS: A SNP in the neurexophilin 2 (NXPH2) gene surpassed genome-wide
      significance (p = 2.06 * 10-8 ), with multiple adjacent markers p < 10-6 , for
      women with anti-Class I alloantibodies only. Little is currently known about the
      function of NXPH2, although gene family members have been shown to impact
      immunity. SNPs in the E2F7 gene, a transcription factor related to cell cycle
      control and cellular proliferation, also approached genomewide significance (p =
      2.5 * 10-7 ). CONCLUSION: Further work to extend the GWAS approach and to
      characterize variants in NXPH2 and E2F7 in the context of alloantibody formation
      is warranted.

PMID- 29168252
TI  - Global substrate specificity profiling of post-translational modifying enzymes.
AB  - Enzymes that modify the proteome, referred to as post-translational modifying
      (PTM) enzymes, are central regulators of cellular signaling. Determining the
      substrate specificity of PTM enzymes is a critical step in unraveling their
      biological functions both in normal physiological processes and in disease
      states. Advances in peptide chemistry over the last century have enabled the
      rapid generation of peptide libraries for querying substrate recognition by PTM
      enzymes. In this article, we highlight various peptide-based approaches for
      analysis of PTM enzyme substrate specificity. We focus on the application of
      these technologies to proteases and also discuss specific examples in which they
      have been used to uncover the substrate specificity of other types of PTM
      enzymes, such as kinases. In particular, we highlight our multiplex substrate
      profiling by mass spectrometry (MSP-MS) assay, which uses a rationally designed,
      physicochemically diverse library of tetradecapeptides. We show how this method
      has been applied to PTM enzymes to uncover biological function, and guide
      substrate and inhibitor design. We also briefly discuss how this technique can be
      combined with other methods to gain a systems-level understanding of PTM enzyme
      regulation and function.

PMID- 29168256
TI  - Alcohol taxes' contribution to prices in high and middle-income countries: Data
      from the International Alcohol Control Study.
AB  - INTRODUCTION: Taxation is increasingly being used as an effective means of
      influencing behaviour in relation to harmful products. In this paper we use data
      from six participating countries of the International Alcohol Control Study to
      examine and evaluate their comparative prices and tax regimes. METHODS: We
      calculate taxes and prices for three high-income and three middle-income
      countries. The data are drawn from the International Alcohol Control survey and
      from the Alcohol Environment Protocol. Tax systems are described and then the
      rates of tax on key products presented. Comparisons are made using the Purchasing
      Power Parity rates. The price and purchase data from each country's International
      Alcohol Control survey is then used to calculate the mean percentage of retail
      price paid in tax weighted by actual consumption. RESULTS: Both ad valorem and
      specific per unit of alcohol taxation systems are represented among the six
      countries. The prices differ widely between countries even though presented in
      terms of Purchasing Power Parity. The percentage of tax in the final price also
      varies widely but is much lower than the 75% set by the World Health Organization
      as a goal for tobacco tax. CONCLUSION: There is considerable variation in tax
      systems and prices across countries. There is scope to increase taxation and this
      analysis provides comparable data, including the percentage of tax in final
      price, from some middle and high-income countries for consideration in policy
      discussion.

PMID- 29168257
TI  - Effect of privatized managed care on public insurance spending and generosity:
      Evidence from Medicaid.
AB  - States choose to provide Medicaid coverage via managed care or traditional fee
      for-service. Managed care provided by private insurers poses higher contracting
      costs and information asymmetry than traditional fee-for-service but potentially
      improves efficiency and reduces spending. Evaluating the effect of managed care
      on Medicaid spending is challenging because adoption of managed care is nonrandom
      and may be driven by local economic shocks that simultaneously affect Medicaid
      spending. This study implements a dynamic panel framework to estimate the effect
      of managed care enrollment on spending levels and program design. Results show
      reductions in Medicaid spending larger than previously found in cross-state
      studies: A 10% increase of managed care enrollment reduces state Medicaid
      spending by 2.94%, or approximately $55 million. The study identifies which areas
      of spending are differentially affected by managed care enrollment and whether
      savings from managed care affect Medicaid design, specifically coverage
      generosity.

PMID- 29168258
TI  - Potential effect of recombinant thrombomodulin on ischemia-reperfusion liver
      injury in rats.
AB  - AIM: Liver ischemia-reperfusion (I/R) injury is a severe complication of liver
      surgery. However, the responsible molecular mechanism remains unclear. High
      mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as
      a damage-associated molecular pattern. The aim of this study is to reveal the
      roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver
      injury. METHODS: Rats underwent partial hepatic ischemia followed by reperfusion,
      and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an
      inhibitor of HMGB1. RESULTS: In rats with I/R injury, the HMGB1 level
      significantly decreased in the liver tissue and significantly increased in the
      serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the
      hepatocytes was observed between the rTM(-) group and rTM(+) group after surgery.
      Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group
      than the rTM(-) group after surgery (P < 0.001). The levels of tumor necrosis
      factor-alpha and interleukin-6 in the liver tissue 24 h after surgery were
      significantly lower in the rTM(+) group than the rTM(-) group (P < 0.001). The
      plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group
      was significantly decreased after surgery compared with that of the rTM(-) group
      (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was
      significantly smaller in the rTM(+) group than the rTM(-) group (P < 0.001).
      CONCLUSIONS: Recombinant thrombomodulin can serve as a treatment for I/R liver
      injury by inhibiting HMGB1.

PMID- 29168259
TI  - Constipation management in people with intellectual disability: A systematic
      review.
AB  - BACKGROUND: Constipation can lead to serious health issues and death. This
      systematic review summarizes international research pertaining to the management
      of constipation in people with intellectual disability. METHOD: Studies published
      from 1990 to 2017 were identified using Medline, Cinahl, PsycINFO, Web of
      Science, email requests and cross-citations. Studies were reviewed narratively in
      relation to identified themes. RESULTS: Eighteen studies were reviewed in
      relation to three themes: laxative receipt; interventions (dietary fibre,
      abdominal massage and macrogol); and staff issues (knowledge and training).
      Laxative polypharmacy was common. Studies report positive results for dietary
      fibre and abdominal massage although study quality was limited. CONCLUSION: The
      main management response to constipation in people with intellectual disability
      is laxative use despite limited effectiveness. An improved evidence base is
      required to support the suggestion that an individualized, integrated bowel
      management programme may reduce constipation and associated health conditions in
      people with intellectual disability.

PMID- 29168260
TI  - Prosystemin, a prohormone that modulates plant defense barriers, is an
      intrinsically disordered protein.
AB  - Prosystemin, originally isolated from Lycopersicon esculentum, is a tomato pro
      hormone of 200 aminoacid residues which releases a bioactive peptide of 18
      aminoacids called Systemin. This signaling peptide is involved in the activation
      of defense genes in solanaceous plants in response to herbivore feeding damage.
      Using biochemical, biophysical and bioinformatics approaches we characterized
      Prosystemin, showing that it is an intrinsically disordered protein possessing a
      few secondary structure elements within the sequence. Plant treatment with
      recombinant Prosystemin promotes early and late plant defense genes, which limit
      the development and survival of Spodoptera littoralis larvae fed with treated
      plants.

PMID- 29168261
TI  - "Impact of drug-reimbursement policies on prescribing: A case-study of a newly
      marketed long-acting injectable antipsychotic among relapsed schizophrenia
      patients".
AB  - OBJECTIVE: To quantify and explain variation in use of long-acting injectable
      antipsychotics (LAIs) in the United States, and understand the relationship
      between patient characteristics, drug reimbursement policies, and LAI prescribing
      after relapse. METHODS: A cohort of recently relapsed patients with schizophrenia
      ages 18 to 64, were identified immediately after discharge from a related
      inpatient hospitalization, partial hospitalization, or emergency room visit,
      drawn from 2004 to 2006 Medicaid claims, and followed for 90 days until LAI
      initiation. Data on state-level Medicaid prior authorization (PA) policies for
      LAIs were collected. Sequential longitudinal Poisson regression models were
      developed to understand the relationship between patient and PA policy variables
      and LAI prescribing, including prior adherence to oral antipsychotics,
      demographics, clinical variables, and presence of PA policy for LAI. RESULTS:
      Among 36 282 patients, 3.1% received risperidone LAI, and 3.8% received a first
      generation (FGA) LAI with wide variation across states. Prior adherence ranged
      from 29% to 89% but was marginally associated with initiation and did not explain
      variation for LAI prescribing. FGA initiation was associated with geography and
      race/ethnicity but not PA policy. For risperidone LAI initiation, demographics
      and clinical factors explained, respectively, 5.0% and 3.0% of the variation; PA
      policy had a large negative association with initiation (RR = 0.41; 95%CI 0.20
      0.87) and explained 8.4% of the variation. CONCLUSIONS: PA policies may represent
      a major treatment barrier for risperidone LAI among relapsed patients. Non
      adherence plays a little role in predicting which patients receive LAIs. Policy
      makers and health insurers will need to consider these findings when guiding the
      use of LAIs. KEY POINTS Among a nationwide cohort of relapsed schizophrenia
      patients enrolled in US Medicaid, 3.1% received Risperdal Consta, a long-acting
      injectable antipsychotic (LAI), and 3.8% initiated a first-generation first
      generation LAI within 90 days after discharge. During 2004 to 2006, there was
      marked variation in 90 day post-relapse initiation of Risperdal-Consta-a newly
      marketed medication during this period-and also marked variation in 90 day post
      relapse initiation of any first-generation LAI, which appeared to be associated
      with race/ethnicity and geography. Prior authorization policies were associated
      with substantially lower initiation of Risperdal Consta in this cohort of
      relapsed patients even after accounting for clinical indication (non-adherence),
      relapse history, demographics, adjunctive medication, and mental health service
      use.

PMID- 29168262
TI  - Cross-border migration and initiation of others into drug injecting in Tijuana,
      Mexico.
AB  - INTRODUCTION AND AIMS: Efforts to prevent injection drug use (IDU) are
      increasingly focusing on the role that people who inject drugs (PWID) play in
      facilitating the entry of others into this behaviour. This is particularly
      relevant in settings experiencing high levels of IDU, such as Mexico's northern
      border region, where cross-border migration, particularly through forced
      deportation, has been found to increase a range of health and social harms
      related to injecting. DESIGN AND METHODS: PWID enrolled in a prospective cohort
      study in Tijuana, Mexico, since 2011 were interviewed semi-annually, which
      solicited responses on their experiences initiating others into injecting.
      Univariate and multivariable logistic regression analyses were conducted at the
      Preventing Injection by Modifying Existing Responses (PRIMER) baseline, with the
      dependent variable defined as reporting ever initiating others into injection.
      The primary independent variable was lifetime deportation from the USA to Mexico.
      RESULTS: Among 532 participants, 14% (n = 76) reported initiating others into
      injecting, the majority of participants reporting initiating acquaintances (74%,
      n = 56). In multivariable analyses, initiating others into injecting was
      independently associated with reporting living in the USA for 1-5 years [adjusted
      odds ratio (AOR) = 2.42; 95% confidence interval (CI) 1.22-4.79, P = 0.01], and
      methamphetamine and heroin injection combined (AOR = 3.67; 95% CI 1.11-12.17, P =
      0.03). Deportation was not independently associated with initiating others into
      injecting. DISCUSSION AND CONCLUSIONS: The impact of migration needs to be
      considered within binational programming seeking to prevent the expansion of
      epidemics of injecting and HIV transmission among mobile populations residing in
      the Mexico-USA border region.

PMID- 29168264
TI  - Beneficial effects of an investigational wristband containing Synsepalum
      dulcificum (miracle fruit) seed oil on the performance of hand and finger motor
      skills in healthy subjects: A randomized controlled preliminary study.
AB  - Miracle fruit (Synsepalum dulcificum) seed oil (MFSO) contains phytochemicals and
      nutrients reported to affect musculoskeletal performance. The purpose of this
      study was to assess the safety and efficacy of a compression wristband containing
      MFSO on its ability to measurably improve the hand and finger motor skills of
      participants. Healthy right-handed participants (n = 38) were randomized in this
      double-blind, placebo-controlled study of MFSO and vehicle wristbands. Subjects
      wore the wristband on their left hand 4-6 weeks and then only on their right hand
      2-4 weeks; the contralateral untreated hand served as an additional control.
      Twelve hand/finger motor skills were measured using quantitative bio
      instrumentation tests, and subject self-assessment questionnaires were conducted.
      With each hand, in 9/12 tests, the MFSO group showed a clinically meaningful
      average improvement compared with an average worsening in the vehicle group.
      Statistical superiority to the control treatment group was exhibited in 9/12
      tests for each hand (p < .01). After discontinuing the MFSO wristband on the left
      hand, test values regressed toward baseline levels. Subjects favored the MFSO
      wristband over the control, rating it as effective in improving their motor
      skills. Use of the MFSO wristband may improve an individual's manual dexterity
      skills and ability to maintain this performance.

PMID- 29168263
TI  - Incidence and predictors of mental health disorder diagnoses among people who
      inject drugs in a Canadian setting.
AB  - INTRODUCTION AND AIMS: Limited attention has been given to the predictors of
      mental health diagnoses among people who inject drugs (PWID) in community
      settings. Therefore, we sought to longitudinally examine the prevalence,
      incidence and predictors of mental disorder diagnosis among a community-recruited
      cohort of PWID. DESIGN AND METHODS: Data were derived from two prospective cohort
      studies of PWID (VIDUS and ACCESS) in Vancouver, Canada between December 2005 and
      May 2015. We used multivariable extended Cox regression to identify factors
      independently associated with self-reported mental disorder diagnosis during
      follow-up among those without a history of such diagnoses at baseline. RESULTS:
      Among the 923 participants who did not report a mental disorder at baseline, 206
      (22.3%) reported a first diagnosis of a mental disorder during follow-up for an
      incidence density of 4.29 [95% confidence interval (CI) 3.72-4.91] per 100 person
      years. In the multivariable analysis, female sex [adjusted hazards ratio (AHR) =
      1.74, 95% CI 1.29-2.33], experiencing non-fatal overdose (AHR = 2.33, 95% CI 1.38
      3.94), accessing any drug or alcohol treatment (AHR = 1.68, 95% CI 1.24-2.27),
      accessing any community health or social services (AHR = 1.53, 95% CI 1.02-2.28)
      and experiencing violence (AHR = 1.60, 95% CI 1.12-2.29) were independently
      associated with a mental disorder diagnosis at follow-up. DISCUSSION AND
      CONCLUSIONS: We observed a high prevalence and incidence of mental disorders
      among our community-recruited sample of PWID. The validity and implication of
      these diagnoses for key substance use and public health outcomes are an urgent
      priority.

PMID- 29168265
TI  - Two-stage identification of SNP effects on dynamic poplar growth.
AB  - This project proposes an approach to identify significant single nucleotide
      polymorphism (SNP) effects, both additive and dominant, on the dynamic growth of
      poplar in diameter and height. The annual changes in yearly phenotypes based on
      regular observation periods are considered to represent multiple responses. In
      total 156,362 candidate SNPs are studied, and the phenotypes of 64 poplar trees
      are recorded. To address this ultrahigh dimensionality issue, this paper adopts a
      two-stage approach. First, the conventional genome-wide association studies
      (GWAS) and the distance correlation sure independence screening (DC-SIS) methods
      (Li et al., 2012) were combined to reduce the model dimensions at the sample
      size; second, a grouped penalized regression was applied to further refine the
      model and choose the final sparse SNPs. The multiple response issue was also
      carefully addressed. The SNP effects on the dynamic diameter and height growth
      patterns of poplar were systematically analyzed. In addition, a series of
      intensive simulation studies was performed to validate the proposed approach.

PMID- 29168266
TI  - Profile analysis of treatment effect changes in eating disorder indicators.
AB  - We investigated differential treatment effects on specific eating disorder (ED)
      indicators to enhance conclusions about treatment efficacy. Profile Analysis via
      Multidimensional Scaling, which identifies core profiles in a population and
      interprets person profiles with core profile information, was utilized to
      identify core profiles from a sample of 5,177 patients who were repeatedly
      measured with the ED inventory-2 at admission and at discharge. To assess
      differential treatment effects for individual ED indicators, we compared the core
      profiles at admission with those at discharge. Three core profiles were
      identified and labeled as High Body Dissatisfaction with Low Bulimia (Core
      Profile 1), High Interoceptive Awareness with Low Body Dissatisfaction (Core
      Profile 2), and High Ineffectiveness with Low Bulimia (Core Profile 3). Treatment
      had the greatest effects on Core Profile 2. The patients whose profile patterns
      were similar to that of Core Profiles 1 and 2 were positively related with weight
      gain. However, treatment was least on Core Profile 3, and the patients whose
      profile patterns were like that of Core Profile 3 were negatively related with
      weight gain. In conclusion, those patients who fit Core Profile 3 may benefit
      from different treatment modalities than those that are standard in inpatient
      settings.

PMID- 29168267
TI  - Explicit and implicit attitudes towards people with intellectual disabilities:
      The role of contact and participant demographics.
AB  - BACKGROUND: Intellectual disability research has concentrated on self-reported
      explicit attitudes with little focus on implicit attitudes. Such attitudes are
      evaluations which occur with or without conscious awareness, respectively. This
      investigation examined participants' (N = 234) attitudes towards individuals with
      intellectual disabilities with reference to participants' gender, age, level of
      education, frequency of contact and closeness. METHOD: UK adults completed
      explicit (ATTID) and implicit attitude (ST-IAT) measures, and provided
      demographics via an online survey. RESULTS: Participant demographics predicted
      explicit attitudes-with differing cognitive, affective and behavioural
      associations. Contact frequency was most significant. Implicit attitudes were not
      predicted, evidencing implicit-explicit attitude differences. CONCLUSIONS: The
      results encourage more implicit-explicit attitude relationship research regarding
      disability. The associations between demographics, contact and implicit attitudes
      should be explored further. Research should question whether implicit attitudes
      reflect participants' true beliefs-denoting less importance to demographics-or
      whether they reflect wider societal values rather than individuals' attitudes.

PMID- 29168268
TI  - Lifetime marijuana use and subclinical atherosclerosis: the Coronary Artery Risk
      Development in Young Adults (CARDIA) study.
AB  - BACKGROUND AND AIMS: Unlike tobacco, the effect of marijuana smoke on subclinical
      atherosclerosis, a surrogate measure for cardiovascular disease, is not known.
      This study aimed to determine the association between lifetime exposure to
      marijuana and measures of subclinical atherosclerosis in mid-life. DESIGN,
      SETTING AND PARTICIPANTS: We used data from the US-based Coronary Artery Risk
      Development in Young Adults (CARDIA) study, a cohort of black and white men and
      women aged 18-30 years at baseline in 1985-86, with up to seven follow-up
      examinations over 25 years. A total of 3498 participants in the CARDIA study were
      included in this study. MEASUREMENTS: Cumulative years of exposure to marijuana
      (expressed in 'marijuana-years', with 1 marijuana-year equivalent to 365 days of
      use) using repeated assessments every 2-5 years for 25 years. Abdominal artery
      calcium (AAC) and coronary artery calcium (CAC) scores were measured by computed
      tomography at year 25 examination. RESULTS: Among 3117 participants with AAC and
      CAC measurements, 2627 (84%) reported past marijuana use and 1536 (49%) past
      daily tobacco smoking. Compared with tobacco smokers, 46% of whom reported 10 or
      more pack-years of use, only 12% of marijuana users reported 5 or more marijuana
      years of use and only 6% reported having used marijuana daily. We found a
      significant interaction between never and ever tobacco users on the association
      between cumulative marijuana use and AAC (P = 0.05). Among those who never smoked
      tobacco, cumulative marijuana-years were not associated with AAC or CAC in models
      adjusted for demographics, cardiovascular risk factors, licit and illicit drug
      exposure and depression symptoms. However, among ever tobacco smokers, marijuana
      exposure was associated with AAC and CAC. At 5 marijuana-years of exposure, using
      AAC = 0 and CAC = 0 as a reference group, the odds ratio (OR) was 1.97 [95%
      confidence interval (CI) = 1.21-3.21, P = 0.007] for AAC > 0/CAC = 0 and 1.83
      (95% CI = 1.02-3.31, P = 0.04) for CAC > 0), regardless of AAC. Tobacco smoking
      was associated strongly with both AAC and CAC. CONCLUSION: Marijuana use appears
      to be associated with subclinical atherosclerosis, but only among ever tobacco
      users.

PMID- 29168269
TI  - Adolescent ethanol intake alters cannabinoid type-1 receptor localization in
      astrocytes of the adult mouse hippocampus.
AB  - Cannabinoid type-1 (CB1 ) receptors are widely distributed in the brain and play
      important roles in astrocyte function and the modulation of neuronal synaptic
      transmission and plasticity. However, it is currently unknown how CB1 receptor
      expression in astrocytes is affected by long-term exposure to stressors. Here we
      examined CB1 receptors in astrocytes of ethanol (EtOH)-exposed adolescent mice to
      determine its effect on CB1 receptor localization and density in adult brain. 4-8
      week-old male mice were exposed to 20 percent EtOH over a period of 4 weeks, and
      receptor localization was examined after 4 weeks in the hippocampal CA1 stratum
      radiatum by pre-embedding immunoelectron microscopy. Our results revealed a
      significant reduction in CB1 receptor immunoparticles in astrocytic processes of
      EtOH-exposed mice when compared with controls (positive astrocyte elements: 21.50
      +/- 2.80 percent versus 37.22 +/- 3.12 percent, respectively), as well as a
      reduction in particle density (0.24 +/- 0.02 versus 0.35 +/- 0.02 particles/MUm).
      The majority of CB1 receptor metal particles were in the range of 400-1200 nm
      from synaptic terminals in both control and EtOH. Altogether, the decrease in the
      CB1 receptor expression in hippocampal astrocytes of adult mice exposed to EtOH
      during adolescence reveals a long lasting effect of EtOH on astrocytic CB1
      receptors. This deficiency may also have negative consequences for synaptic
      function.

PMID- 29168270
TI  - A comparative evaluation of a new fully automated assay for von Willebrand factor
      collagen binding activity to an established method.
AB  - INTRODUCTION: Laboratory diagnosis of von Willebrand disease (VWD) is made by the
      measurement of von Willebrand factor (VWF) protein level and its activities.
      Current VWF activity tests include ristocetin cofactor and collagen binding
      (VWF:CB) assays. AIM: We have undertaken an evaluation of a new fully automated
      VWF:CB assay relative to an established enzyme-linked immunosorbent assay (ELISA)
      method. METHODS: The two analytical systems operate with different detection
      principles: a chemiluminescent method performed on ACL AcuStar Analyzer (the
      former) and a colorimetric ELISA by Asserachrom Stago (the latter) (type III
      collagen from human placenta). The HemosIL AcuStar VWF:CB assay is a
      chemiluminescent 2-step immunoassay that uses magnetic particles coated with a
      type III collagen triple-helical peptide. VWF:CB levels were determined in 50
      healthy subjects and 100 VWD patients (22 type 1, 73 type 2 and 5 type 3).
      RESULTS: Eleven VWD samples reported VWF:CB values below the lower detection
      limit of one or both methods. The new method showed a good correlation with the
      ELISA method (r > .9, mean bias 3.85 IU/dL) in both healthy and VWD samples. One
      of 150 samples gave inconsistent results using the two assays, leading to an
      uncertain diagnosis of VWD type 1 (ELISA method) or type 2 MCB (fully automated
      method). CONCLUSION: The new assay is rapid and simple to use, with its ready-to
      use reagent cartridges. This VWF:CB assay, in addition to the measurement of
      VWF:Ag and VWF:RCo made on the same platform, gives additional information for
      the diagnosis of VWD in both nonspecialized and reference laboratories.

PMID- 29168271
TI  - N-Methyl-d-aspartate receptor co-agonist availability affects behavioral and
      neurochemical responses to cocaine: insights into comorbid schizophrenia and
      substance abuse.
AB  - Both schizophrenia (SZ) and substance abuse (SA) exhibit significant
      heritability. Moreover, N-methyl-d-aspartate receptors (NMDARs) have been
      implicated in the pathophysiology of both SZ and SA. We hypothesize that the high
      prevalence of comorbid SA in SZ is due to dysfunction of NMDARs caused by shared
      risk genes. We used transgenic mice with a null mutation of the gene encoding
      serine racemase (SR), the enzyme that synthesizes the NMDAR co-agonist d-serine
      and an established risk gene for SZ, to recreate the pathology of SZ. We
      determined the effect of NMDAR hypofunction resulting from the absence of d
      serine on motivated behavior by using intracranial self-stimulation and
      neurotransmitter release in the nucleus accumbens by using in vivo microdialysis.
      Compared with wild-type mice, SR-/- mice exhibited similar baseline intracranial
      self-stimulation thresholds but were less sensitive to the threshold-lowering
      (rewarding) and the performance-elevating (stimulant) effects of cocaine. While
      basal dopamine (DA) and glutamate release were elevated in the nucleus accumbens
      of SR-/- mice, cocaine-induced increases in DA and glutamate release were
      blunted. gamma-Amino-butyric acid efflux was unaffected in the SR-/- mice.
      Together, these findings suggest that the impaired NMDAR function and a
      consequent decrease in sensitivity to cocaine effects on behavior are mediated by
      blunted DA and glutamate responses normally triggered by the drug. Projected to
      humans, NMDAR hypofunction due to mutations in SR or other genes impacting
      glutamatergic function in SZ may render abused substances less potent and
      effective, thus requiring higher doses to achieve a hedonic response, resulting
      in elevated drug exposure and increased dependence/addiction.

PMID- 29168272
TI  - Peanut oral immunotherapy dose variations do not result in allergic reactions.

PMID- 29168273
TI  - Synergistic inhibition of cell proliferation by combined targeting with kinase
      inhibitors and dietary xanthone is a promising strategy for melanoma treatment.
AB  - alpha-Mangostin is a dietary xanthone that displays various biological
      activities, and numerous reports have shown its efficacy in cancer prevention and
      inhibition. As most agents have been shown to be ineffective as single-agent
      therapy for malignant melanoma (MM), the principle of targeted chemotherapy for
      MM is to use effective inhibitors and combination methods. In this study, we
      tested the cytotoxicity of several kinase inhibitors, including the glycogen
      synthase kinase (GSK)-3 inhibitor CHIR99021, and rapamycin, in combination with a
      dietary xanthone, alpha-mangostin, by screening from a kinase inhibitor library
      for melanogenesis in SK-MEL-2 MM cells, and verified these by clone formation
      efficiency, terminal dUTP nick end labelling, and expression of apoptosis-related
      proteins. We also explored the molecular mechanisms for the apoptosis-inducing
      effects reported. We found a marked synergistic effect of CHIR99021 or rapamycin
      in combination with alpha-mangostin, which we verified through apoptosis-related
      methods. These data provide a strong rationale for the use of alpha-mangostin as
      an adjunct to GSK-3 inhibitor or mammalian target of rapamycin inhibitor
      treatment. The intrinsic mechanism behind alpha-mangostin might be inhibition of
      phosphatidylinositol 3-kinase/AKT signalling and autophagy, and induction of
      reactive oxygen species generation.

PMID- 29168274
TI  - Antimicrobial properties of calcium hydroxide dressing when used for long-term
      application: A systematic review.
AB  - This review aims to evaluate the antimicrobial efficacy of calcium hydroxide
      against endodontic pathogens when used for 7 days or longer. A systematic
      electronic literature search was performed in the PubMed, Embase and EBSCO
      Dentistry & Oral Sciences Source databases using appropriate key words to
      identify investigations written in the English language that examined the
      association between the contact time of intracanal calcium hydroxide dressing and
      its antimicrobial properties. There were no exclusions based on study design. The
      search yielded 6993 publications. After duplicate removal, 5913 publications were
      identified and 11 studies met the inclusion criteria. Results showed that the
      antimicrobial effect of calcium hydroxide for contact times ranging between seven
      and 45 days is comparable. Two studies demonstrated contradictory findings when
      exposure was extended to more than 45 days. Future studies are warranted to
      investigate and optimise calcium hydroxide application for longer periods and
      identify the potential benefits of its use in clinical settings.

PMID- 29168276
TI  - Established and novel measures of upper limb impairment in children with Charcot
      Marie-tooth disease type 1A and riboflavin transporter deficiency type 2.
AB  - Hand function is a problem in patients with Charcot-Marie-Tooth disease type 1A
      (CMT1A) and Riboflavin Transporter Deficiency type 2 (RTD2). However, a detailed
      understanding of upper limb involvement in these conditions is lacking. The aim
      of this pilot study was to compare hand and upper limb function between children
      with CMT1A, RTD2 and healthy controls using established and novel outcome
      measures. Three age-and sex-matched groups of four children (5-15 years, 1
      male/group) with CMT1A, RTD2, and healthy controls were assessed for function,
      strength, and sensation. Fatigue and muscle activity of the FDI was also assessed
      using a submaximal contraction at 40% of the participants' maximal voluntary
      contraction. Functional measures were most affected in children with RTD2
      followed by children with CMT1A, compared to healthy controls. Strength was
      similarly impaired in CMT1A and RTD2 compared to controls (p < 0.05). Sensation
      was significantly impaired in RTD2 compared to CMT1A and controls (p = 0.008).
      While time to fatigue did not differ between groups, a decline in muscle activity
      while force remained constant showed that controls compensated with other muscles
      during the fatigue task while children with CMT1A and RTD2 did not have this
      compensatory ability. Children with CMT1A and RTD2 exhibited marked hand/upper
      limb impairment. These results suggest the upper limb should be a focus of
      rehabilitative therapy in affected children using sensitive outcome measures of
      strength and sensation, as well as functional activities of daily living, which
      are most relevant to the patient.

PMID- 29168275
TI  - 6-shogaol induces apoptosis and enhances radiosensitivity in head and neck
      squamous cell carcinoma cell lines.
AB  - Ginger (Zingiber officinale Roscoe) is used for a wide array of conditions in
      traditional medicine in Asia, but little is known about the effect on head and
      neck cancer. In this study, the effect of two major pharmacologically active
      compounds of ginger, 6-gingerol and 6-shogaol, were studied on head and neck
      cancer cell lines. Furthermore, experiments in combination with established
      treatment methods for head and neck cancer were performed. Proliferation assays
      showed a dose-dependent reduction of cell viability. Flow cytometry analysis
      revealed the induction of apoptosis. Western blot analysis indicated that the
      antiapoptotic protein survivin was suppressed after treatment. Although a
      combination of 6-shogaol with cisplatin exhibited no synergistic effect, the
      combination with irradiation showed a synergistic reduction of clonogenic
      survival. In conclusion, ginger compounds have many noteworthy effects on head
      and neck cancer cell lines. In particular, the enhancement of radiosensitivity is
      remarkable.

PMID- 29168277
TI  - Congenital limb deficiencies and major associated anomalies in Alberta for the
      years 1980-2012.
AB  - There is a wide range of the proportion of congenital anomalies associated with
      limb deficiencies reported in the literature. This variation is primarily
      attributed to methodology and classification differences. The distribution of
      associated anomalies among cases with congenital limb deficiencies in Alberta
      born between January 1, 1980 and December 31, 2012 is described. Of the 170 cases
      identified, most were live born (75.3%), male (61.8%), had longitudinal limb
      deficiencies (78.8%), and had associated anomalies outside the musculoskeletal
      system (77.6%). Significant associations between the preaxial longitudinal group
      and the central nervous, gastrointestinal, and cardiovascular systems are
      reported as well as between the postaxial longitudinal group and congenital hip
      and foot anomalies. Probable and possible syndrome diagnoses are described for
      cases with recognized malformation patterns.

PMID- 29168278
TI  - A role for intravenous immunoglobulin in the treatment of Acquired Von Willebrand
      Syndrome associated with IgM gammopathy.

PMID- 29168279
TI  - Photocatalytic Oxygen Evolution from Functional Triazine-Based Polymers with
      Tunable Band Structures.
AB  - Conjugated polymers (CPs) are emerging and appealing light harvesters for
      photocatalytic water splitting owing to their adjustable band gap and facile
      processing. Herein, we report an advanced mild synthesis of three conjugated
      triazine-based polymers (CTPs) with different chain lengths by increasing the
      quantity of electron-donating benzyl units in the backbone. Varying the chain
      length of the CTPs modulates their electronic, optical, and redox properties,
      resulting in an enhanced performance for photocatalytic oxygen evolution, which
      is the more challenging half-reaction of water splitting owing to the sluggish
      reaction kinetics. Our results could stimulate interest in these functional
      polymers where a molecular engineering strategy enables the production of
      suitable semiconductor redox energetics for oxygenic photosynthesis.

PMID- 29168280
TI  - Quaternary beta2,2 -Amino Acids: Catalytic Asymmetric Synthesis and Incorporation
      into Peptides by Fmoc-Based Solid-Phase Peptide Synthesis.
AB  - beta-Amino acid incorporation has emerged as a promising approach to enhance the
      stability of parent peptides and to improve their biological activity. Owing to
      the lack of reliable access to beta2,2 -amino acids in a setting suitable for
      peptide synthesis, most contemporary research efforts focus on the use of beta3 -
      and certain beta2,3 -amino acids. Herein, we report the catalytic asymmetric
      synthesis of beta2,2 -amino acids and their incorporation into peptides by Fmoc
      based solid-phase peptide synthesis (Fmoc-SPPS). A quaternary carbon center was
      constructed by the palladium-catalyzed decarboxylative allylation of 4
      substituted isoxazolidin-5-ones. The N-O bond in the products not only acts as a
      traceless protecting group for beta-amino acids but also undergoes amide
      formation with alpha-ketoacids derived from Fmoc-protected alpha-amino acids,
      thus providing expeditious access to alpha-beta2,2 -dipeptides ready for Fmoc
      SPPS.

PMID- 29168281
TI  - A review of urban impacts on avian life-history evolution: Does city living lead
      to slower pace of life?
AB  - The concept of a pace-of-life syndrome describes inter- and intraspecific
      variation in several life-history traits along a slow-to-fast pace-of-life
      continuum, with long lifespans, low reproductive and metabolic rates, and
      elevated somatic defences at the slow end of the continuum and the opposite
      traits at the fast end. Pace-of-life can vary in relation to local environmental
      conditions (e.g. latitude, altitude), and here we propose that this variation may
      also occur along an anthropogenically modified environmental gradient. Based on a
      body of literature supporting the idea that city birds have longer lifespans, we
      predict that urban birds have a slower pace-of-life compared to rural birds and
      thus invest more in self maintenance and less in annual reproduction. Our
      statistical meta-analysis of two key traits related to pace-of-life, survival and
      breeding investment (clutch size), indicated that urban birds generally have
      higher survival, but smaller clutch sizes. The latter finding (smaller clutches
      in urban habitats) seemed to be mainly a characteristic of smaller passerines. We
      also reviewed urbanization studies on other traits that can be associated with
      pace-of-life and are related to either reproductive investment or self
      maintenance. Though sample sizes were generally too small to conduct formal meta
      analyses, published literature suggests that urban birds tend to produce lower
      quality sexual signals and invest more in offspring care. The latter finding is
      in agreement with the adult survival hypothesis, proposing that higher adult
      survival prospects favour investment in fewer offspring per year. According to
      our hypothesis, differences in age structure should arise between urban and rural
      populations, providing a novel alternative explanation for physiological
      differences and earlier breeding. We encourage more research investigating how
      telomere dynamics, immune defences, antioxidants and oxidative damage in
      different tissues vary along the urbanization gradient, and suggest that applying
      pace-of-life framework to studies of variation in physiological traits along the
      urbanization gradient might be the next direction to improve our understanding of
      urbanization as an evolutionary process.

PMID- 29168282
TI  - Risk factors for asthma occurrence in children with early-onset atopic
      dermatitis: An 8-year follow-up study.
AB  - BACKGROUND: Children with early-onset atopic dermatitis (AD) are at substantial
      risk of developing asthma later in life, and identifying the critical window of
      detrimental exposure is advantageous for implementing preventive actions. The aim
      of this study was to evaluate the role of exposure to environmental modifiers
      during pregnancy and early childhood in asthma occurrence in an infantile AD
      cohort. METHODS: Eligible study participants were selected from the Taiwan Birth
      Cohort Study, which enrolled 24 200 newborns in 2005. We enrolled those cases who
      had been diagnosed as having AD before 3 years of age and followed them up till
      age 8. We excluded those ever diagnosed with asthma before AD onset. The
      dependent variable was defined in terms of whether the participant was diagnosed
      as having asthma before 8 years of age. We applied logistic regression models to
      evaluate the risks of exposure to different determinants in asthma occurrence.
      RESULTS: A total of 1549 children with AD had completed the 8-year follow-up, and
      334 (21.6%) of them had asthma. The results revealed that male sex, lower birth
      order, maternal asthma history, maternal obesity before pregnancy, and
      environmental tobacco smoke exposure before 3 years of age were significant risk
      factors for further development of asthma. Furthermore, food allergy during early
      life, lower respiratory tract infection, and longer durations of symptomatic AD
      influenced asthma development later in life. CONCLUSIONS: The findings confirmed
      the critical determinants for asthma occurrence in infantile AD, which may enable
      a more personalized approach to the prevention of asthma.

PMID- 29168283
TI  - Emotion Regulation as a Transdiagnostic Feature Among Eating Disorders: Cross
      sectional and Longitudinal Approach.
AB  - Emotion regulation (ER) difficulties are observed in eating disorders (EDs).
      However, few studies have explored ER before and after treatment. The aims are as
      follows: to explore ER difficulties across ED types and a healthy control (HC)
      group (Study 1) and to assess pretreatment and post-treatment changes among ED
      types (Study 2). In Study 1, adult women with EDs (n = 438) and HC (n = 126)
      completed an assessment including Eating Disorders Inventory-2, Difficulties in
      Emotion Regulation Scale and Symptom Checklist-90-Revised. Patients in Study 2 (n
      = 69) were also reassessed after treatment. All ED types reported worse ER
      compared with HC (p < .001); also, ER differences were found between ED types.
      Prospective analyses show ER improvements after treatment (p < .001; |d| = 0.51),
      especially in patients with bulimia nervosa (p < .001; |d| = 1.03; Reliable
      Change Index = 9.79) with greater improvement in those with a better treatment
      outcome (p = .034). In conclusion, emotion dysregulation is a part of all forms
      of EDs. Furthermore, emotional dysregulation can be modified. ED treatments for
      anorexia nervosa and binge eating disorder might be enhanced by targeting ER
      skills. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders
      Association.

PMID- 29168284
TI  - Association of Preoperative Serum Total Cholesterol Level with Postoperative Pain
      Outcomes after Laparoscopic Surgery for Gastric Cancer.
AB  - BACKGROUND: Opioid usage is reportedly increased in patients with advanced cancer
      and low total cholesterol (TC). The aim of this study was to determine the
      effects of preoperative serum TC levels on postoperative opioid usage in patients
      undergoing laparoscopic gastric cancer surgery. METHODS: We retrospectively
      analyzed the medical records of patients with gastric cancer who underwent
      laparoscopic gastrectomy at our institution between January 1, 2011 and July 31,
      2017. We investigated the correlation between TC levels in the month before
      surgery and numeric rating scale (NRS) scores and opioid consumption on
      postoperative days (PODs) 0 to 3. The patients were stratified according to
      preoperative TC level (< 160 mg/dL, low; 160 to 199 mg/dL, medium; >= 200 mg/dL,
      high). RESULTS: TC and NRS scores (PODs 0, 1) for 1,919 eligible patients showed
      weak but significant positive coefficients (0.074 and 0.098 on POD 0 and POD 1,
      respectively, P < 0.01). After adjusting for confounders, there were no
      significant differences in postoperative NRS scores on PODs 0, 1, 2, or 3 or in
      oral morphine equivalents on PODs 0 to 3 according to TC level. CONCLUSION:
      Preoperative serum TC levels have no effect on pain outcomes in the 3 days
      following laparoscopic gastric surgery.

PMID- 29168285
TI  - Peutz -Jeghers syndrome (PJS).

PMID- 29168287
TI  - Multiplicity of skin cancers in Queensland and their cost burden to government
      and patients.
AB  - OBJECTIVE: To determine the cost burden to government and patients for
      individuals with multiple skin cancers. METHODS: We used self-reported baseline
      data on socio-demographics, phenotype and sun exposure behaviours from
      participants in the QSkin Sun and Health Study with at least one
      histopathologically confirmed keratinocyte cancer or melanoma (n=5,673). Linkage
      to Australian Medicare data (2011-2014) provided resource data and government and
      out-of-pocket patient costs. Generalised linear models examined costs by
      frequency of skin cancer groups separately for melanoma and keratinocyte cancer.
      RESULTS: Over three years, 539 participants were diagnosed with melanoma (11% had
      >=2 melanomas) and 5,134 participants were treated for keratinocyte cancers (10%
      had >=6). Median Medicare costs per person were $1,325 (maximum $6,117) for >=2
      melanomas and $2,126 (maximum $54,618) for >=6 keratinocyte cancers. Increased
      costs were associated with private health insurance. CONCLUSIONS: Individuals who
      are multiply affected by skin cancers are relatively common and the accompanying
      individual and government cost burden can be substantial. These findings support
      skin cancer being classified as a chronic disease. Implications for public
      health: Over time, the economic burden for skin cancer for individuals and health
      providers is high and investment in prevention remains important from an economic
      viewpoint.

PMID- 29168286
TI  - Comparative proteomic profiling reveals a role for Cisd2 in skeletal muscle
      aging.
AB  - Skeletal muscle has emerged as one of the most important tissues involved in
      regulating systemic metabolism. The gastrocnemius is a powerful skeletal muscle
      composed of predominantly glycolytic fast-twitch fibers that are preferentially
      lost among old age. This decrease in gastrocnemius muscle mass is remarkable
      during aging; however, the underlying molecular mechanism is not fully
      understood. Strikingly, there is a ~70% decrease in Cisd2 protein, a key
      regulator of lifespan in mice and the disease gene for Wolfram syndrome 2 in
      humans, within the gastrocnemius after middle age among mice. A proteomics
      approach was used to investigate the gastrocnemius of naturally aged mice, and
      this was compared to the autonomous effect of Cisd2 on gastrocnemius aging using
      muscle-specific Cisd2 knockout (mKO) mice as a premature aging model.
      Intriguingly, dysregulation of calcium signaling and activation of UPR/ER stress
      stand out as the top two pathways. Additionally, the activity of Serca1 was
      significantly impaired and this impairment is mainly attributable to irreversibly
      oxidative modifications of Serca. Our results reveal that the overall
      characteristics of the gastrocnemius are very similar when naturally aged mice
      and the Cisd2 mKO mice are compared in terms of pathological alterations,
      ultrastructural abnormalities, and proteomics profiling. This suggests that Cisd2
      mKO mouse is a unique model for understanding the aging mechanism of skeletal
      muscle. Furthermore, this work substantiates the hypothesis that Cisd2 is crucial
      to the gastrocnemius muscle and suggests that Cisd2 is a potential therapeutic
      target for muscle aging.

PMID- 29168288
TI  - Robotic Strong's procedure for the treatment of superior mesenteric artery
      syndrome. Description of surgical technique on occasion of the first reported
      case in the literature.
AB  - BACKROUND: Superior Mesenteric Artery Syndrome (SMAS) is a rare disorder caused
      by compression of the third portion of the duodenum by the SMA. Once a
      conservative approach fails, usual surgical strategies include Duodenojejunostomy
      and Strong's procedure. The latter avoids potential anastomotic risks and
      complications. Robotic Strong's procedure (RSP) combines both the benefits of a
      minimal invasive approach and also enchased robotic accuracy and efficacy.
      METHODS: For a young girl who was unsuccessfully treated conservatively, the
      paper describes the RSP surgical technique. To the authors' knowledge, this is
      the first report in the literature. RESULTS: Minimal blood loss, short operative
      time, short hospital stay and early recovery were the short-term benefits.
      Significant weight gain was achieved three months after the surgery. CONCLUSION:
      Based on primary experience, it is suggested that RSP is a very effective
      alternative in treating SMAS.

PMID- 29168289
TI  - Cannabinoids for nausea and vomiting related to chemotherapy: Overview of
      systematic reviews.
AB  - Nausea and vomiting are common and distressing adverse events of chemotherapy.
      This review focuses on the findings and quality of systematic reviews (SRs) of
      cannabinoids for chemotherapy-induced nausea and vomiting (CINV). Review of SRs,
      a systematic literature search, was conducted in several electronic databases and
      included SRs evaluating cannabinoids for CINV in cancer patients. Methodological
      quality and quality of reporting were evaluated by AMSTAR and PRISMA,
      respectively. Initial search retrieved 2,206 records, and 5 SRs were included. On
      the basis of findings of the sole SR judged as high methodological quality,
      cannabinoids seem to be more effective than placebo, equal to prochlorperazine
      for reducing CINV, and to be preferred by patients. The response to different
      combinations of antiemetic agents seems to be equal to 1 antiemetic alone. The
      average of AMSTAR score was 5, and the average of PRISMA score was 13.2.
      Cannabinoids represent a valuable option for treating CINV, despite the adverse
      events related to treatment, such as drowsiness and cognitive impairment. There
      is no good quality evidence to recommend or not the use of cannabinoids for CINV.
      More studies are still needed to evaluate the effectiveness of cannabinoids when
      compared with modern antiemetics.

PMID- 29168291
TI  - The COL5A3 and MMP9 genes interact in eczema susceptibility.
AB  - BACKGROUND: Genetic studies of eczema have identified many genes, which explain
      only 14% of the heritability. Missing heritability may be partly due to ignored
      gene-gene (G-G) interactions. OBJECTIVE: Our aim was to detect new interacting
      genes involved in eczema. METHODS: The search for G-G interaction in eczema was
      conducted using a two-step approach, which included as a first step, a biological
      selection of genes, which are involved either in the skin or epidermis
      development or in the collagen metabolism, and as a second step, an interaction
      analysis of the selected genes. Analyses were carried out at both SNP and gene
      levels in three asthma-ascertained family samples: the discovery dataset of 388
      EGEA (Epidemiological study on the Genetics and Environment of Asthma) families
      and the two replication datasets of 253 SLSJ (Saguenay-Lac-Saint-Jean) families
      and 207 MRCA (Medical Research Council) families. RESULTS: One pair of SNPs,
      rs2287807 in COL5A3 and rs17576 in MMP9, that were detected in EGEA at P <= 10-5
      showed significant interaction by meta-analysis of EGEA, SLSJ and MRCA samples (P
      = 1.1 * 10-8 under the significant threshold of 10-7 ). Gene-based analysis
      confirmed strong interaction between COL5A3 and MMP9 (P = 4 * 10-8 under the
      significant threshold of 4 * 10-6 ) by meta-analysis of the three datasets. When
      stratifying the data on asthma, this interaction remained in both groups of
      asthmatic and non-asthmatic subjects. CONCLUSION: This study identified
      significant interaction between two new genes, COL5A3 and MMP9, which may be
      accounted for by a degradation of COL5A3 by MMP9 influencing eczema
      susceptibility. Further confirmation of this interaction as well as functional
      studies is needed to better understand the role of these genes in eczema.

PMID- 29168292
TI  - Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of
      diclofenac in healthy human volunteers.
AB  - The purpose of present study was to evaluate the effect of quercetin on
      pharmacokinetics of diclofenac sodium (DIC) in healthy volunteers. The open
      label, 2 period, sequential study was conducted in 12 healthy volunteers. DIC 100
      mg was administered during control and after quercetin phases. Quercetin 500 mg
      was administered twice daily for 10 days during quercetin phase. Treatment with
      quercetin significantly enhanced maximum plasma concentration (Cmax ), area under
      the curve (AUC0-infinity ), and half life, while significantly decreased
      elimination rate constant (kel ) and apparent oral clearance (CL/F) of DIC
      compared with control. On the other hand, Cmax and AUC0-infinity of 4
      hydroxydiclofenac (4-OHDIC) were decreased after quercetin treatment. In
      addition, geometric mean ratios and 90% confidence intervals for Cmax and AUC0
      infinity of DIC and 4-OHDIC were both out of the no-effect limits of 0.80-1.25,
      which indicates a significant pharmacokinetic interaction between quercetin and
      DIC. Furthermore, quercetin treatment significantly decreased metabolic ratios of
      Cmax and AUC0-infinity suggesting that reduced formation of DIC to 4-OHDIC. The
      results suggest that quercetin might have inhibited CYP2C9-mediated metabolism of
      DIC. Accordingly, caution should be taken when quercetin is used in combination
      with therapeutic drugs metabolized by CYP2C9, and dose adjustment of CYP2C9
      substrates may be necessary.

PMID- 29168293
TI  - Changes in intraepidermal nerve fiber and Langerhans cell densities in the
      plantar skin of rats after mercuric chloride exposure.
AB  - Mercury and its compounds possess strong neurotoxicity and patients with mercury
      poisoning often report pain and numbness in the distal extremities that conform
      to the "stocking-glove" pattern. However, no study has investigated whether
      damage to small nerve fibers is associated with mercury poisoning. The aims of
      the present study were to evaluate the effects of different doses of mercury
      chloride (HgCl2 ) on intraepidermal nerve fibers density (IENFD) and Langerhans
      cells (LCs) in the plantar skin of rats and to assess the possible relationship
      between changes in IENFD and sensory testing. Male Sprague-Dawley rats were
      divided into three experimental groups and administered HgCl2 solutions via
      gavage at three different doses (4.25, 8.5, and 17 mg/kg/day) for 21 days.
      Subsequently, behavioral tests and pathological changes in IENFD and LCs were
      assessed at three different time points (1, 2, and 3 weeks). Rats in all three
      HgCl2 groups exhibited varying degrees of weight and hair loss. Thermal
      hypersensitivity was evident in all the HgCl2 groups (for middle-2w subgroup, p <
      0.05). Mechanical sensitivity tests revealed hyposensitivity in all the HgCl2
      groups except the high-1w subgroup. Significant decreases in IENFD (for the high
      1w, middle-1w, low-2w, and low-3w subgroups, p < 0.05) and significant increases
      in the density of LCs (except for the low-1w and high-2w subgroups, all p < 0.05)
      were found in all groups after HgCl2 exposure. An association analysis revealed a
      significant correlation between the decrease in IENFD and the increase in LCs
      densities (r = -0.573, p < 0.01). The present study demonstrated a decrease in
      IENFD and an increase in LCs density in the plantar skin of rats after HgCl2
      poisoning, indicating that damage of the small nerve fibers occurs after mercury
      poisoning.

PMID- 29168290
TI  - Gating the holes in the Swiss cheese (part I): Expanding professor Reason's model
      for patient safety.
AB  - INTRODUCTION: Although patient safety has improved steadily, harm remains a
      substantial global challenge. Additionally, safety needs to be ensured not only
      in hospitals but also across the continuum of care. Better understanding of the
      complex cognitive factors influencing health care-related decisions and
      organizational cultures could lead to more rational approaches, and thereby to
      further improvement. HYPOTHESIS: A model integrating the concepts underlying
      Reason's Swiss cheese theory and the cognitive-affective biases plus cascade
      could advance the understanding of cognitive-affective processes that underlie
      decisions and organizational cultures across the continuum of care. METHODS:
      Thematic analysis, qualitative information from several sources being used to
      support argumentation. DISCUSSION: Complex covert cognitive phenomena underlie
      decisions influencing health care. In the integrated model, the Swiss cheese
      slices represent dynamic cognitive-affective (mental) gates: Reason's successive
      layers of defence. Like firewalls and antivirus programs, cognitive-affective
      gates normally allow the passage of rational decisions but block or counter
      unsounds ones. Gates can be breached (ie, holes created) at one or more levels of
      organizations, teams, and individuals, by (1) any element of cognitive-affective
      biases plus (conflicts of interest and cognitive biases being the best studied)
      and (2) other potential error-provoking factors. Conversely, flawed decisions can
      be blocked and consequences minimized; for example, by addressing cognitive
      biases plus and error-provoking factors, and being constantly mindful. Informed
      shared decision making is a neglected but critical layer of defence (cognitive
      affective gate). The integrated model can be custom tailored to specific
      situations, and the underlying principles applied to all methods for improving
      safety. The model may also provide a framework for developing and evaluating
      strategies to optimize organizational cultures and decisions. LIMITATIONS: The
      concept is abstract, the model is virtual, and the best supportive evidence is
      qualitative and indirect. CONCLUSIONS: The proposed model may help enhance
      rational decision making across the continuum of care, thereby improving patient
      safety globally.

PMID- 29168296
TI  - Novel STRA6 null mutations in the original family described with Matthew-Wood
      syndrome.

PMID- 29168295
TI  - Lean psoas area does not correlate with clinical outcomes in moderately to
      severely injured older people.
AB  - OBJECTIVE: Frailty has been associated with worse outcomes in older trauma
      patients. Specifically, the utility of lean cross-sectional psoas muscle area
      (LPA) was examined as a potentially simple objective measure of frailty. METHODS:
      Five hundred and fifty-four patients over the age of 65 were admitted with trauma
      between 2011 and 2014. Two hundred and twenty-five of these had adequate computed
      tomography imaging available for analysis. Cross-sectional area of the psoas
      muscle at the inferior endplate of L4 was quantified. RESULTS: Multivariate
      regression analysis showed no significant correlation between LPA and outcomes of
      mortality (P = 0.82) or inpatient complications (P = 0.22). Injury Severity Score
      (ISS) had a strong association with both mortality (odds ratio (OR) 9.5; 95%
      confidence interval (CI) 2.9-30.9) and inpatient complications (OR 9.9; 95% CI
      3.5-27.7). Age also had an association with mortality (OR 1.09; 95% CI 1.03-1.16)
      and inpatient complications (OR 1.06; 95% CI 1.01-1.12). CONCLUSION: Lean psoas
      area was not an independent predictor of mortality or complications in a cohort
      of injured older patients.

PMID- 29168294
TI  - Association of prenatal folate status with early childhood wheeze and atopic
      dermatitis.
AB  - BACKGROUND: Prenatal folic acid supplementation is recommended to prevent birth
      defects. Some foods are fortified in the USA to ensure sufficient intake among
      reproductive-aged women. However, high prenatal folate exposure may be a risk
      factor for childhood atopic diseases. We investigated associations between
      prenatal folate and early childhood wheeze and atopic dermatitis in a US cohort.
      METHODS: We studied 858 mother-child dyads, enrolled prenatally. Folate was
      measured in 2nd and 3rd trimester maternal plasma. Parents reported current
      wheeze (previous 12 months) and healthcare provider diagnosis of atopic
      dermatitis at 3 years. We examined associations using logistic regression,
      modeling folate continuously and dichotomously (< or >=20 ng/mL), a level often
      considered supraphysiologic. RESULTS: Over half of women were African American
      and on Medicaid. Median (interquartile range) folate levels were 22.6 (15.9-30.0)
      and 23.1 (16.1-30.0) ng/mL for 2nd and 3rd trimesters, respectively. Current
      wheeze and atopic dermatitis were reported for 20.4% and 26.8% of children,
      respectively. Second trimester folate as a continuous exposure was not
      significantly associated with outcomes. Decreased odds of current wheeze were
      observed in children born to mothers who had 2nd trimester folate >=20 ng/mL
      (adjusted odds ratios = 0.67, 95% confidence interval = 0.46, 0.97) compared to
      children with maternal levels <20 ng/mL. Third trimester folate was not
      associated with outcomes. CONCLUSIONS: High plasma folate in mid-pregnancy was
      associated with decreased odds of current wheeze at age 3. Our findings do not
      support harmful effects of high prenatal folate levels on childhood atopic
      diseases in this setting.

PMID- 29168298
TI  - Biallelic mutations in NALCN: Expanding the genotypic and phenotypic spectra of
      IHPRF1.
AB  - Loss-of function mutations in NALCN on chromosome 13q, a sodium leak channel that
      maintains baseline neuronal excitability, cause infantile hypotonia with
      psychomotor retardation and characteristic faces 1 (IHPRF1, OMIM #615419). Here,
      we document two individuals with early onset hypotonia with poor feeding and
      intellectual disability who were compatible with a diagnosis of IHPRF1. The two
      patients had bi-allelic mutations in NALCN through two different genetic
      mechanisms: Patient 1 had bi-allelic splice site mutations, that is c.1267-2A>G,
      derived from heterozygous parents, while Patient 2 had a partial maternal
      uniparental isodisomy that harbored a frameshift mutation, that is
      c.2022_2023delAT, in chromosome 13 that was detected through a dedicated
      algorithm for homozygosity data mapping in whole exome sequencing. The
      delineation of the exact pattern of inheritance provided vital information
      regarding the risk of recurrence. In animal models with Nalcn mutations, two
      behavioral phenotypes, that are, postnatal dyspnea and sleep disturbance, have
      been reported. Our observations of the two patients with postnatal dyspnea and
      one patient with sleep disturbance support an association between these two
      behavioral phenotypes and NALCN mutations in humans. The routine use of a
      detection algorithm for homozygosity data mapping might improve the diagnostic
      yields of next-generation sequencing.

PMID- 29168297
TI  - Single suture craniosynostosis: Identification of rare variants in genes
      associated with syndromic forms.
AB  - We report RNA-Sequencing results on a cohort of patients with single suture
      craniosynostosis and demonstrate significant enrichment of heterozygous, rare,
      and damaging variants among key craniosynostosis-related genes. Genetic burden
      analysis identified a significant increase in damaging variants in ATR, EFNA4,
      ERF, MEGF8, SCARF2, and TGFBR2. Of 391 participants, 15% were found to have
      damaging and potentially causal variants in 29 genes. We observed transmission in
      96% of the affected individuals, and thus penetrance, epigenetics, and oligogenic
      factors need to be considered when recommending genetic testing in patients with
      nonsyndromic craniosynostosis.

PMID- 29168299
TI  - 17alpha-estradiol acts through hypothalamic pro-opiomelanocortin expressing
      neurons to reduce feeding behavior.
AB  - Weight loss is an effective intervention for diminishing disease burden in obese
      older adults. Pharmacological interventions that reduce food intake and thereby
      promote weight loss may offer effective strategies to reduce age-related disease.
      We previously reported that 17alpha-estradiol (17alpha-E2) administration elicits
      beneficial effects on metabolism and inflammation in old male mice. These
      observations were associated with reduced calorie intake. Here, we demonstrate
      that 17alpha-E2 acts through pro-opiomelanocortin (Pomc) expression in the
      arcuate nucleus (ARC) to reduce food intake and body mass in mouse models of
      obesity. These results confirm that 17alpha-E2 modulates appetite through
      selective interactions within hypothalamic anorexigenic pathways. Interestingly,
      some peripheral markers of metabolic homeostasis were also improved in animals
      with near complete loss of ARC Pomc transcription. This suggests that 17alpha-E2
      might have central and peripheral actions that can beneficially affect metabolism
      cooperatively or independently.

PMID- 29168300
TI  - Elevated distress, race/ethnicity age, education, income, and type of cancer: It
      is complicated.

PMID- 29168301
TI  - Animal models used in furcation perforation studies: A systematic review and
      comprehensive synthesis of model characteristics.
AB  - In order to systematise furcation perforation (FP) experimental animal models
      described in the literature and to determine whether there is evidence that a
      model is superior to others, MEDLINE/PubMed, SciELO and Cochrane Library were
      searched to find studies which used animal models of FP. Data were gathered
      concerning model characteristics, chosen groups, sample numbers, type of
      outcomes, journal and main area studied. Twenty-five articles were included in
      this systematic review, four conducted in rodent models, three in non-human
      primates and 18 in dogs. Medians were six animals and 34 teeth per study; 10
      teeth per test group and, when performed, six teeth per control group. Twenty
      four studies investigated the use of materials for FP repair; eight also tested
      adjuvant materials/substances. Although there is no model which can be described
      as ideal and superior than others for FP studies, dogs appear to possess the most
      suitable model characteristics.

PMID- 29168302
TI  - Analysing and Navigating Natural Products Space for Generating Small, Diverse,
      But Representative Chemical Libraries.
AB  - Armed with the digital availability of two natural products libraries, amounting
      to some 195 885 molecular entities, we ask the question of how we can best sample
      from them to maximize their "representativeness" in smaller and more usable
      libraries of 96, 384, 1152, and 1920 molecules. The term "representativeness" is
      intended to include diversity, but for numerical reasons (and the likelihood of
      being able to perform a QSAR) it is necessary to focus on areas of chemical space
      that are more highly populated. Encoding chemical structures as fingerprints
      using the RDKit "patterned" algorithm, we first assess the granularity of the
      natural products space using a simple clustering algorithm, showing that there
      are major regions of "denseness" but also a great many very sparsely populated
      areas. We then apply a "hybrid" hierarchical K-means clustering algorithm to the
      data to produce more statistically robust clusters from which representative and
      appropriate numbers of samples may be chosen. There is necessarily again a trade
      off between cluster size and cluster number, but within these constraints,
      libraries containing 384 or 1152 molecules can be found that come from clusters
      that represent some 18 and 30% of the whole chemical space, with cluster sizes
      of, respectively, 50 and 27 or above, just about sufficient to perform a QSAR. By
      using the online availability of molecules via the Molport system
      (www.molport.com), we are also able to construct (and, for the first time,
      provide the contents of) a small virtual library of available molecules that
      provided effective coverage of the chemical space described. Consistent with
      this, the average molecular similarities of the contents of the libraries
      developed is considerably smaller than is that of the original libraries. The
      suggested libraries may have use in molecular or phenotypic screening, including
      for determining possible transporter substrates.

PMID- 29168303
TI  - Fall risk assessment tools for use among older adults in long-term care settings:
      A systematic review of the literature.
AB  - OBJECTIVE: To conduct a systematic review of published fall risk assessment tools
      (FRATs) tested for predictive validity among older adults in long-term care
      (LTC). METHODS: A systematic search was conducted using five databases. Only
      studies reporting on sensitivity and specificity values, conducted in LTC on
      populations primarily aged over 60 years, were considered. RESULTS: Fifteen
      papers were included and three different categories of FRATs emerged:
      multifactorial assessment tools, functional mobility assessments and algorithms.
      Several FRATs showed moderate-to-good predictive validity and reliability, with
      the Modified Fall Assessment Tool and the Peninsula Health Falls Risk Assessment
      Tool (PHFRAT) also demonstrating good feasibility. CONCLUSION: Evidence for the
      best choice of FRAT for use in LTC remains limited. Further research is warranted
      for the PHFRAT, recommended for use in LTC by best practice guidelines, before
      its establishment as the tool of choice for these clinical settings.

PMID- 29168304
TI  - Aboriginal children and penicillin injections for rheumatic fever: how much of a
      problem is injection pain?
AB  - OBJECTIVE: To explore young Aboriginal people's and clinicians' experiences of
      injection pain for the 10 years of penicillin injections children are prescribed
      to prevent rheumatic fever recurrences. METHODS: Aboriginal children on the
      penicillin regimen and clinicians were purposively recruited from four remote
      sites in Australia. Semi-structured interviews and participant observations were
      conducted. Views were synthesised and thematically analysed. RESULTS: A total of
      29 Aboriginal children and 59 clinicians were interviewed. Sixteen participants
      appeared to become accustomed to the injection pain, eight did not find pain an
      issue, and five found injection pain difficult. A further five believed the
      injections made them unwell. Patients expressed varying abilities to negotiate
      with clinicians about the use of pain reduction measures. Clinicians revealed
      good knowledge of pain reduction measures, but offered them inconsistently. All
      clinicians found administering the injections distressing. CONCLUSION: Repeated
      painful procedures in children necessitate well-planned and child-focused care.
      Current practices are not in line with guidance from the Royal Australasian
      College of Physicians about effects of repeated painful procedures on children.
      Initiating the long-term injection regimen for rheumatic fever is a special event
      requiring expert input. A newly reported finding of a subset of young people
      feeling unwell after receiving the injection requires further investigation.
      Implications for public health: Improvement of local and jurisdictional
      guidelines on use of pain reduction measures for children who have been
      prescribed repeated painful injections for rheumatic fever is needed.

PMID- 29168305
TI  - The Trajectory of Anhedonic and Depressive Symptoms in Anorexia Nervosa: A
      Longitudinal and Cross-Sectional Approach.
AB  - Anhedonia, the inability to experience pleasure, is associated with depression,
      schizophrenia and also anorexia nervosa (AN). However, it remains unanswered
      whether anhedonic symptoms in AN are undernutrition-dependent depressive symptoms
      or a core feature of AN. Therefore, we aim at investigating the trajectory of
      anhedonic and depressive symptoms over the course of the disorder. Self-reported
      symptoms were collected in 35 nonmedicated acutely ill, 33 long-term recovered
      patients and 62 healthy females. The majority of the acutely ill (n = 24) were
      followed up after >15% weight restoration (short-term recovery). Anhedonia was
      found to be increased during the acute, short-term as well as long-term recovered
      state while depressive symptoms showed a reduction over time. Additionally,
      depressive symptoms were negatively associated with body mass index in acute
      patients. This provides evidence of anhedonia being a trait-characteristic of AN,
      relatively unrelated to undernutrition-dependent depressive symptoms. Results are
      discussed with regard to implications for treatment and prevention. Copyright (c)
      2017 John Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 29168306
TI  - Improving New Zealand's preparations for the next pandemic.

PMID- 29168307
TI  - Optimising residential respite care in nursing homes: Current problems and
      solutions for a better future.
AB  - AIM: To examine whether residential respite care increases the risk of harm to
      older people and suggest directions for future research and policy. BACKGROUND:
      Respite care is a vital part of the aged care system that supports dependent
      older people and their caregivers to continue residing in the community. There is
      little research determining whether an older person experiences harm from
      residential respite. METHODS: This commentary considered conceptual research and
      existing empirical evidence to determine whether the risk of death was greater
      during residential respite care for older people. RESULTS: Evidence on the
      mortality in contemporary respite care is extremely limited with the majority of
      studies published almost 20 years ago and focussing on planned respite
      admissions. The evidence available has limitations in design and lacks comparison
      groups and key variables relevant to outcome and risk stratification.
      Nonetheless, it provides a theoretical basis supporting that the potential for
      harm and mortality may be increased during a residential respite care admission.
      CONCLUSIONS: The question of whether residential respite care presents
      significant risks to older people remains unanswered. Substantial changes in
      practice since the last century make the existing empirical evidence redundant.
      However, there is much to learn by reflecting on omissions of important details
      from these studies. IMPLICATIONS FOR PRACTICE: A full and objective understanding
      of the harm associated with residential respite care for older people requires
      reopening and re-examining this area with robust research. Informed professional
      nursing practice and policy requires an empirical evidence basis to residential
      respite care.

PMID- 29168308
TI  - Demonstrating Improved Multiple Transport-Mean-Free-Path Imaging Capabilities of
      Light Sheet Microscopy in the Quantification of Fluorescence Dynamics.
AB  - Optical microscopy constitutes, one of the most fundamental paradigms for the
      understanding of complex biological mechanisms in the whole-organism and live
      tissue context. Novel imaging techniques such as light sheet fluorescence
      microscopy (LSFM) and optical projection tomography (OPT) combined with phase
      retrieval algorithms (PRT) can produce highly resolved 3D images in multiple
      transport-mean-free-path scales. Our study aims to exemplify the microscopic
      capabilities of LSFM when imaging protein dynamics in Caenorhabditis elegans and
      the distribution of necrotic cells in cancer cell spheroids. To this end, we
      apply LSFM to quantify the spatio-temporal localization of the GFP-tagged aging
      and stress response factor DAF-16/FOXO in transgenic C. elegans. Our analysis
      reveals a linear nuclear localization of DAF-16::GFP across tissues in response
      to heat stress, using a system that outperforms confocal scanning fluorescent
      microscopy in imaging speed, 3D resolution and reduced photo-toxicity.
      Furthermore, we present how PRT can improve the depth-to-resolution-ratio when
      applied to image the far-red fluorescent dye DRAQ7 which stains dead cells in a
      T47D cancer cell spheroid recorded with a customized OPT/LSFM system. Our studies
      demonstrate that LSFM combined with our novel approaches enables higher
      resolution and more accurate 3D quantification than previously applied
      technologies, proving its advance as new gold standard for fluorescence
      microscopy.

PMID- 29168309
TI  - Soldier-biased gene expression in a subterranean termite implies functional
      specialization of the defensive caste.
AB  - In a termite colony, reproduction is typically monopolized by a small number of
      sexuals that are supported by reproductively altruistic soldiers and workers. We
      expect caste differentiation to be associated with clear-cut differences in gene
      expression, and for these differences to reflect caste function and development.
      Here, we use RNA-Sequencing to compare the gene expression profiles of sexual
      nymphs and two non-reproductive helper castes (i.e., workers and soldiers) of the
      Eastern subterranean termite Reticulitermes flavipes. We found that of n = 93
      genes that are strictly expressed as a function of caste, a majority (78%) show a
      soldier-specific pattern. This conspicuous soldier-bias in genome-wide expression
      suggests that this defensively specialized caste is functionally well
      differentiated from both the reproductive and the other non-reproductive caste of
      this species, despite a shared developmental program with workers. Gene ontology
      analysis supports the notion of functional specialization by soldiers, as soldier
      biased gene sets are enriched for novel biological processes. Whether this
      pattern reflects ancient or more recent bouts of selection for caste novelty at
      the gene-regulatory level is not known, but because soldiers are sterile and thus
      have no direct fitness, any selection for novelty must have been mediated
      indirectly, through reproducing relatives.

PMID- 29168310
TI  - A pilot pharmacokinetic study of miroestrol and deoxymiroestrol on rabbit sera
      using polyclonal antibody-based icELISA analysis.
AB  - Miroestrol (ME) and deoxymiroestrol (DME) are the most potent phytoestrogens and
      bioactive markers in Pueraria candollei var. mirifica tuberous roots. To
      understand their pharmacokinetic profiles, a pharmacokinetic study of ME and DME,
      at 0.43 and 0.21 mg per kg body weight, respectively, in three rabbits was
      performed after orally administering a single dose of P. candollei var. mirifica
      enriched fraction extract. Two established polyclonal antibody-based indirect
      competitive enzyme-linked immunosorbent assays were validated to determine ME and
      DME in rabbit sera. In rabbits, the area under the 0- to 48-hr concentration-time
      curve of ME and DME were 854.92 and 1,692.84 ng.h/ml, respectively. The maximum
      concentration of ME was measured 1 hr after administration as 69.62 +/- 8.28
      ng/ml, and the maximum concentration of DME was measured at 3 hr as 81.8 +/- 5.43
      ng/ml. These results provide an initial approach for designing and studying the
      relationship between the ME and DME levels and their therapeutic effects based on
      their pharmacokinetic profiles.

PMID- 29168311
TI  - Usefulness of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein
      in children with primary sclerosing cholangitis.
AB  - BACKGROUND: Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ 
      M2BP) is a novel serum marker of hepatic fibrosis in adults with chronic
      hepatitis C. However, it remains unclear whether serum WFA+ -M2BP levels are
      associated with the progression of liver histology in primary sclerosing
      cholangitis (PSC). METHODS: Twenty-eight children and adolescents with pediatric
      onset PSC (male : female patient ratio, 20:8; median age at diagnosis, 9 years)
      were enrolled in this study. The relation between serum WFA+ -M2BP levels and
      clinical characteristics was retrospectively evaluated. Moreover, receiver
      operating characteristic (ROC) analysis was used to determine whether serum WFA+ 
      M2BP levels could be a reliable marker to identify PSC patients with advanced
      liver histology. RESULTS: According to the Ludwig classification of liver
      histological stage, 28 patients were classified into the four stages. The WFA+ 
      M2BP level, aspartate aminotransferase (AST) to platelet ratio index (APRI), and
      hyaluronic acid correlated significantly with liver histological stage. Moreover,
      WFA+ -M2BP showed a significant positive correlation (P < 0.05) with autoimmune
      hepatitis overlap, AST, alanine aminotransferase (ALT), gamma
      glutamyltransferase, total bilirubin, immunoglobulin G, APRI, and hyaluronic
      acid. A ROC analysis was undertaken to distinguish the patients with advanced
      stage disease (stage 3-4) from those with early stage disease (stage 0-2). It
      showed that WFA+ -M2BP yielded the highest area under the ROC curve value (0.898)
      among four surrogate makers (APRI, 0.850; Fibrosis-4 index, 0.806; and AST/ALT
      ratio, 0.802). Moreover, WFA+ -M2BP yielded the highest sensitivity, specificity,
      positive predictive value, and negative predictive value among the four markers.
      CONCLUSIONS: Serum WFA+ -M2BP levels are useful to identify patients with
      advanced liver histology in pediatric PSC.

PMID- 29168312
TI  - Curcumin mediated down-regulation of alphaV beta3 integrin and up-regulation of
      pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer
      cells.
AB  - Erlotinib is a potent, selective, and orally active inhibitor of the epidermal
      growth factor receptor, but the development of erlotinib resistance during
      chemotherapy can lead to treatment failure. To shed light on the erlotinib
      resistant pathway, this study investigated the effect of combination therapy
      using curcumin- and erlotinib-loaded nanoparticles on the expression of alphav
      beta3 integrin and pyruvate dehydrogenase kinase 4 (PDK4) in an erlotinib
      resistant SW480 colon cancer cell line. An erlotinib-resistant SW480 colon cancer
      cell line was produced by long-term exposure to erlotinib. Curcumin-loaded
      Methoxy poly ethylene glycol Poly caprolactone (cur/mPEG-PCL) and erlotinib
      loaded mPEG-PCL (erl/mPEG-PCL) micelles were provided using a single step
      nanoprecipitation method and used as combination therapy of resistant SW480
      cancer cells. After that, gene expression levels of PDK4, alphav, and beta3 mRNA
      were determined by the semiquantitative reverse transcription-polymerase chain
      reaction. Protein levels of whole alphav beta3 integrin were evaluated using the
      enzyme-linked immunosorbent assay method. In SW480 cell line, the IC50 of
      nonresistant and resistant cells was 87.6 +/- 1.2 nM and 19.1 +/- 0.14 MUM, for
      erlotinib and it was about 21.8 and 30 MUM for curcumin, respectively. Although
      PDK4 expression was not significantly different in resistant and nonresistant
      cells, its expression was up regulated (1.4 fold) in resistant cells by a
      combination therapy of cur/mPEG-PCL at a dose of 3 MUM and erl/mPEG-PCL at a dose
      of 5 MUM. beta3 mRNA and the protein level of whole alphav beta3 integrin was
      significantly higher in resistant SW480 cells as compared with those in
      nonresistant cells. In terms of treatment, a combination of 6-MUM cur/mPEG-PCL
      and 5-MUM erl/mPEG-PCL down regulated beta3 gene expression 6.6-fold in resistant
      cells as compared with nonresistant cells. At the protein level, a combination of
      3-MUM-cur/mPEG-PCL and 10-MUM erl/mPEG-PCL reduced alphav beta3 protein in
      resistant cells. The results indicated that combination therapy using cur/mPEG
      PCL and erl/mPEG-PCL could decrease alphav beta3 integrin expression and increase
      PDK4 gene expression in resistant colon cancer cells, which may have effects on
      drug resistance signaling pathways.

PMID- 29168314
TI  - Elevated plasma and vitreous levels of leucine-rich-alpha2-glycoprotein are
      associated with diabetic retinopathy progression.
AB  - PURPOSE: To investigate the association of plasma and vitreous leucine-rich
      alpha2-glycoprotein (LRG1) with diabetic retinopathy (DR) progression. METHODS: A
      total of 86 outpatients and 33 inpatients were recruited. Outpatients with type 2
      diabetes mellitus (T2DM) were classified as T2DM without DR (n = 22),
      nonproliferative DR (NPDR) (n = 20) and proliferative DR (PDR) (n = 22) based on
      international clinical DR severity scales. A total of 86 plasma and 33 vitreous
      samples were collected and subjected to enzyme-linked immunosorbent assay. The
      diagnostic value of plasma LRG1 was tested using receiver operating
      characteristic (ROC) curves. RESULTS: Plasma LRG1 in PDR patients (9025 +/- 1870
      pg/ml) was significantly increased as compared with controls (5975 +/- 2022
      pg/ml), T2DM without DR (6550 +/- 2359 pg/ml) and NPDR patients (6550 +/- 2359
      pg/ml) (p < 0.0001). Vitreous LRG1 in PDR patients was elevated by approximately
      4.3-fold than that in controls (562.1 +/- 273.5 ng/ml versus 130.0 +/- 102.8
      ng/ml, p = 0.000). The area under the ROC curve value for plasma LRG1 was 0.786
      (p < 0.0001). The maximal Youden index was 0.4372 and the optimal cut-off value
      of LRG1 was 7357.043 pg/ml with 81.82% sensitivity and 61.90% specificity.
      CONCLUSION: Plasma and vitreous LRG1 levels were elevated in patients with PDR.
      Leucine-rich-alpha2-glycoprotein (LRG1) might be a potential risk-warning marker
      for PDR.

PMID- 29168313
TI  - Children with blindness - major causes, developmental outcomes and implications
      for habilitation and educational support: a two-decade, Swedish population-based
      study.
AB  - PURPOSE: The aim was to describe the population of children with congenital or
      early infancy blindness in Sweden, with regard to causes of blindness and
      prevalence of neurodevelopmental impairments. METHODS: Medical, psychological and
      pedagogical records of Swedish children with congenital or early infancy
      blindness (total blindness or light perception at the most) born in 1988-2008
      were analysed regarding year of birth, gender, cause of blindness, gestational
      age, associated neurological disorders/syndromes, associated neurodevelopmental
      impairments, cognitive level and type of school placement. RESULTS: A total of
      150 individuals, 80 girls and 70 boys, were identified, corresponding to a
      prevalence of 7/100 000. Five causes of blindness dominated, constituting 76% of
      all represented aetiologies: retinopathy of prematurity (ROP), optic nerve
      hypoplasia (ONH), Leber congenital amaurosis (LCA), optic nerve atrophy (ONA) and
      microphthalmia/anophthalmia. Nearly three of four children in the study
      population had at least one additional disability besides blindness; the most
      common being intellectual disability (ID) and autism spectrum disorder (ASD).
      More than half of the population had more than one additional disability. Autism
      spectrum disorder (ASD) was most common in children with ONH, ROP, LCA and
      microphthalmia/anophthalmia. CONCLUSION: In children born within the last
      decades, isolated blindness is uncommon and the rate of multidisabilities is
      high. Autism spectrum disorder (ASD) seems to be more strongly associated with
      specific aetiological subgroups. Further development of the support to families
      and schools should be based on knowledge about the considerable heterogeneity of
      the population of children with blindness, and the common occurrence of
      coexisting neurodevelopmental disorders, especially ID and ASD.

PMID- 29168315
TI  - Postoperative efficacy analysis of patients with facial nerve palsy associated
      with cholesteatoma otitis media: Our experience with 32 patients.

PMID- 29168317
TI  - Hepatitis C virus prevalence and associated risk factors among Indigenous
      Australians who inject drugs.
AB  - OBJECTIVE: To examine factors associated with hepatitis C virus (HCV) infection
      among a national sample of Indigenous and non-Indigenous people who inject drugs
      (PWID) in Australia. METHODS: Respondents were recruited from Australia's Needle
      Syringe Program Survey; an annual bio-behavioural surveillance project that
      monitors HCV antibody prevalence among PWID. Data from 2006-2015 were de
      duplicated to retain only one record where individuals participated in >1 survey
      round. Univariate and multivariable logistic regression examined demographic
      characteristics and injection-related behaviours associated with exposure to HCV.
      RESULTS: Among 17,413 respondents, 2,215 (13%) were Indigenous Australians.
      Compared to their non-Indigenous counterparts, Indigenous respondents were
      significantly more likely to be exposed to HCV infection (53% vs. 60%
      respectively, p<0.001). Among Indigenous respondents, HCV antibody positivity was
      independently associated with a history of imprisonment (Adjusted Odd Ratio [AOR]
      2.13, 95%CI 1.73-2.64), opioid injection (AOR 1.53, 95%CI 11.43-2.16),
      recruitment in a metropolitan location (AOR 1.27, 95%CI 1.02-1.59), engagement in
      opioid substitution therapy (AOR 2.83, 95%CI 2.23-3.59) and length of time since
      first injection (p<0.001). CONCLUSION: Indigenous PWID are more likely to be
      exposed to HCV infection than their non-Indigenous counterparts. Implications for
      public health: Increased access to culturally sensitive harm reduction programs
      is required to prevent primary HCV infection and reinfection among Indigenous
      PWID. Given recent advances in HCV treatment, promotion of treatment uptake among
      Indigenous PWID may reduce future HCV-related morbidity and mortality.

PMID- 29168318
TI  - Validation of X-ray Wavefunction Refinement.
AB  - In this work, the quality of the electron density in crystals reconstructed by
      the multipolar model (MM) and by X-ray wavefunction refinement (XWR) is tested on
      a set of high-resolution X-ray diffraction data sets of four amino acids and six
      tripeptides. It results in the first thorough validation of XWR. Agreement
      statistics, figures of merit, residual- and deformation-density maps, as well as
      atomic displacement parameters are used to measure the quality of the
      reconstruction relative to the measured structure factors. Topological analysis
      of the reconstructed density is carried out to obtain atomic and bond-topological
      properties, which are subsequently compared to the values derived from
      benchmarking periodic DFT geometry optimizations. XWR is simultaneously in better
      agreement than the MM with both benchmarking theory and the measured diffraction
      pattern. In particular, the obvious problems with the description of polar bonds
      in the MM are significantly reduced by using XWR. Similarly, modeling of electron
      density in the vicinity of hydrogen atoms with XWR is visibly improved.

PMID- 29168316
TI  - Outer dense fibers stabilize the axoneme to maintain sperm motility.
AB  - Outer dense fibers (ODFs), as unique accessory structures in mammalian sperm, are
      considered to play a role in the protection of the sperm tail against shear
      forces. However, the role and relevant mechanisms of ODFs in modulating sperm
      motility and its pathological involvement in asthenozoospermia were unknown.
      Here, we found that the percentage of ODF defects was higher in asthenozoospermic
      samples than that in control samples and was significantly correlated with the
      percentage of axoneme defects and non-motile sperm. Furthermore, the expression
      levels of ODF major components (Odf1, 2, 3, 4) were frequently down-regulated in
      asthenozoospermic samples. Intriguingly, the positive relationship between ODF
      size and sperm motility existed across species. The conditional disruption of
      Odf2 expression in mice led to reduced sperm motility and the characteristics of
      asthenozoospermia. Meanwhile, the expression of acetylated alpha-tubulin was
      decreased in sperm from both Odf2 conditional knockout (cKO) mice and
      asthenozoospermic men. Immunofluorescence and biochemistry analyses showed that
      Odf2 could bind to acetylated alpha-tubulin and protect the acetylation level of
      alpha-tubulin in HEK293T cells in a cold environment. Finally, we found that
      lithium elevated the expression levels of Odf family proteins and acetylated
      alpha-tubulin, elongated the midpiece length and increased the percentage of
      rapidly moving sperm in mice. Our results demonstrate that ODFs are beneficial
      for sperm motility via stabilization of the axoneme and that hypo-expression of
      Odf family proteins is involved in the pathogenesis of asthenozoospermia. The
      lithium administration assay will provide valuable insights into the development
      of new treatments for asthenozoospermia.

PMID- 29168319
TI  - Hospital-based routine HIV testing in high-income countries: a systematic
      literature review.
AB  - OBJECTIVES: To produce a summary of the published evidence of the barriers and
      facilitators for hospital-based routine HIV testing in high-income countries.
      METHODS: Electronic databases were searched for studies, which described the
      offer of HIV testing to adults attending emergency departments (EDs) and acute
      medical units (AMUs) in the UK and US, published between 2006 and 2015. Other
      high-income countries were not included, as their guidelines do not recommend
      routine testing for HIV. The main outcomes of interest were HIV testing uptake,
      HIV testing coverage, factors facilitating HIV screening and barriers to HIV
      testing. Fourteen studies met the pre-defined inclusion criteria and critically
      appraised using mixed methods appraisal tool (MMAT). RESULTS: HIV testing
      coverage ranged from 9.7% to 38.3% and 18.7% to 26% while uptake levels were high
      (70.1-84% and 53-75.4%) in the UK and US, respectively. Operational barriers such
      as lack of time, the need for training and concerns about giving results and
      follow-up of HIV positive results, were reported. Patient-specific factors
      including female sex, old age and low risk perception correlated with refusal of
      HIV testing. Factors that facilitated the offer of HIV testing were venous
      sampling (vs. point-of-care tests), commitment of medical staff to HIV testing
      policy and support from local HIV specialist providers. CONCLUSIONS: There are
      several barriers to routine HIV testing in EDs and AMUs. Many of these stem from
      staff fears about offering HIV testing due to the perceived lack of knowledge
      about HIV. Our systematic review highlights areas which can be targeted to
      increase coverage of routine HIV testing.

PMID- 29168321
TI  - Effect of fetal and infant growth on respiratory symptoms in preterm-born
      children.
AB  - OBJECTIVES: Fetal growth and rapid postnatal weight gain are associated with
      adverse respiratory outcomes in childhood. However, the preterm-born population
      is less well studied. We assessed if the increased respiratory symptoms
      associated with altered fetal growth and infant weight gain were mediated by
      early factors. STUDY DESIGN: We used data from our cohort of preterm- and term
      born (n = 4284 and 2865) children, aged 1-10 years. Respiratory outcomes obtained
      from a respiratory questionnaire were regressed on measures of fetal growth and
      infant weight gain, defined as >0.67 SD change in fetal measurement or weight
      between birth and nine months of age, then adjusted for covariates. We used
      mediation analysis to investigate which variables were effect modifiers. RESULTS:
      Accelerated fetal growth between the 1st trimester and birth (OR 2.01; 95%CI
      1.25, 2.32), and between the 2nd trimester and birth (1.60; 1.15, 2.22) was
      associated with increased wheeze-ever in preterm-born children. Rapid infant
      weight gain was associated with increased wheeze-ever (1.22; 1.02, 1.45);
      children born <=32 weeks' gestation exhibiting rapid weight gain had fivefold
      higher risk of wheeze-ever compared to term-born without weight gain. Current
      maternal smoking and gestational age were identified as candidate mediating
      effects. CONCLUSIONS: Our study suggested that antenatal and postnatal growth
      rates are important for future respiratory health in preterm-born children, and
      that their effects may be mediated by modifiable factors. Minimizing exposure to
      environmental pollutants, especially maternal tobacco smoking, may improve
      outcomes.

PMID- 29168320
TI  - Pulmonary hypertension in the premature infant population: Analysis of
      echocardiographic findings and biomarkers.
AB  - OBJECTIVE: Extremely low gestational age neonates (ELGANs) are at risk for
      pulmonary hypertension (PH). We hypothesized that PH, defined by echocardiogram
      at 36 weeks gestational age (GA), would associate with respiratory morbidity,
      increased oxidant stress, and reduced nitric oxide production. STUDY DESIGN:
      ELGANs in the Vanderbilt fraction of the Prematurity and Respiratory Outcomes
      Program (PROP) who had echocardiograms at 36 +/- 1 weeks GA were studied.
      Echocardiogram features of PH were compared with clinical characteristics as well
      as markers of oxidant stress and components of the nitric oxide pathway.
      Biomarkers were obtained at enrollment (median day 3), 7, 14, and 28 days of
      life. RESULTS: Sixty of 172 infants had an echocardiogram at 36 weeks; 11 had
      evidence of PH. Infants did not differ by PH status in regards to demographics,
      respiratory morbidity, or oxidant stress. However, odds of more severe PH were
      significantly higher in infants with higher nitric oxide metabolites (NOx) at
      enrollment and with a lower citrulline level at day 7. CONCLUSIONS: Respiratory
      morbidity may not always associate with PH at 36 weeks among ELGANs. However,
      components of nitric oxide metabolism are potential biologic markers of PH in
      need of further study.

PMID- 29168322
TI  - Biosynthetically Guided Structure-Activity Relationship Studies of Merochlorin A,
      an Antibiotic Marine Natural Product.
AB  - The onset of new multidrug-resistant strains of bacteria demands continuous
      development of antibacterial agents with new chemical scaffolds and mechanisms of
      action. We present the first structure-activity relationship (SAR) study of 16
      derivatives of a structurally novel antibiotic merochlorin A that were designed
      using a biosynthetic blueprint. Our lead compounds are active against several
      Gram-positive bacteria such as Staphylococcus aureus (SA), methicillin-resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) and
      Bacillus subtilis, inhibit intracellular growth of Mycobacterium bovis, and are
      relatively nontoxic to human cell lines. Furthermore, derivative 12 c {(+/-)
      (3aR,4S,5R,10bS)-5-bromo-7,9-dimethoxy-4-methyl-4-(4-methylpent-3-en-1-yl)-2
      (propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methanobenzo[e]azulene-6,11
      dione} was found to inhibit the growth of Bacillus Calmette-Guerin (BCG)-infected
      cells at concentrations similar to rifampicin. These results outperform the
      natural product, underscoring the potential of merochlorin analogues as a new
      class of antibiotics.

PMID- 29168323
TI  - Disability-based discrimination and health: findings from an Australian-based
      population study.
AB  - OBJECTIVE: Among working-age Australian adults with a disability, we assess the
      association between disability-based discrimination and both overall health and
      psychological distress. METHODS: Using data from the 2015 Australian Bureau of
      Statistics Survey of Disability, Ageing and Carers we estimated the proportion of
      working-age women and men (15-64 years) with disability who report disability
      based discrimination by socio-demographic characteristics and assessed the
      association between disability-based discrimination and self-reported health and
      psychological distress. RESULTS: Nearly 14% of Australians with disability
      reported disability-based discrimination in the previous year. Disability-based
      discrimination was more common among people living in more disadvantaged
      circumstances (unemployed, low income, lower-status occupations), younger people
      and people born in English-speaking countries. Disability-based discrimination
      was associated with higher levels of psychological distress (OR: 2.53, 95%CI:
      2.11, 3.02) and poorer self-reported health (OR: 1.63, 95%CI: 1.37, 1.95).
      CONCLUSION: Disability-based discrimination is a prevalent, important determinant
      of health for Australians with disability. Implications for public health:
      Disability-based discrimination is an under-recognised public health problem that
      is likely to contribute to disability-based health inequities. Public health
      policy, research and practice needs to concentrate efforts on developing policy
      and programs that reduce discrimination experienced by Australians with
      disability.

PMID- 29168324
TI  - Environmental levels of avian antigen are relevant to the progression of chronic
      hypersensitivity pneumonitis during antigen avoidance.
AB  - BACKGROUND: In chronic hypersensitivity pneumonitis (chronic HP), antigen
      avoidance is critical for disease management; however, complete avoidance is
      difficult because of unrecognized exposure to antigens. Recently, we revealed
      that the amount of avian antigen (AAA) in household dust at the time of diagnosis
      predicted the progression of chronic bird-related HP. The purpose of this study
      is to evaluate the relationship between the prognosis of chronic bird-related HP
      and the AAA that remained in the environment during antigen avoidance. METHODS:
      First, we measured the AAA in household dust of 28 consecutive patients (22 with
      chronic bird-related HP and 6 with acute bird-related HP) and 12 healthy
      volunteers. Second, we measured the AAA and collected questionnaires on the
      environmental conditions of the homes of 53 patients with various lung diseases,
      including bird-related HP, to investigate the environmental parameters related to
      a higher AAA. Finally, we prospectively recruited 14 consecutive patients with
      chronic bird-related HP, measured the AAA periodically, and collected clinical
      data. RESULTS: The AAA was higher in patients with chronic bird-related HP at the
      time of diagnosis compared to healthy volunteers and was highest in patients with
      acute bird-related HP. Logistic regression analysis showed that birds frequenting
      a residence was the only significant factor for a higher AAA (odds ratio, 5.686;
      95%CI, 1.263-25.59; P = 0.024). There was a correlation between the mean AAA and
      decline of vital capacity for 1 year (r = -0.55; 95%CI -0.84 to -0.01; P =
      0.043). CONCLUSION: Measurements of the AAA after diagnosis predict the
      progression of chronic bird-related HP. Avian antigen can exist in the indoor
      environment regardless of antigen avoidance. The presence of avian antigen in the
      indoor environment can be attributed to wild birds found outdoors.

PMID- 29168325
TI  - Use of factor concentrates for the management of perioperative bleeding: guidance
      from the SSC of the ISTH.

PMID- 29168328
TI  - Coating of optical fiber with a smart thermosensitive polymer for the separation
      of phthalate esters by solid-phase microextraction.
AB  - A solid-phase microextraction fiber was prepared by coating an optical fiber with
      a temperature-sensitive polymer to determine phthalate esters. N
      Isopropylacrylamide and N,N'-methylenebisacrylamide were used as the monomer and
      the cross linker, respectively. The fabricated fiber was characterized by FTIR
      spectroscopy, thermogravimetric analysis, and scanning electron microscopy.
      During extraction, important factors such as extraction time, pH, temperature,
      and ionic strength were optimized. The fabricated fiber, which is firm,
      inexpensive, stable, and efficient, is a vital material used in solid-phase
      microextraction. Under optimum conditions, the calibration curve was linear and
      in the range of 1-20 MUg/L (r2  = 0.9747). The high extraction efficiency was
      obtained for phthalates with a detection limit of 0.12 MUg/L. The fabricated
      fiber was successfully applied to the solid-phase micro extraction of phthalates
      from water samples after its extraction, followed by gas chromatography with
      flame ionization detection.

PMID- 29168326
TI  - Guidelines in CHARGE syndrome and the missing link: Cranial imaging.
AB  - "CHARGE syndrome" is a complex syndrome with high and extremely variable
      comorbidity. As a result, clinicians may struggle to provide accurate and
      comprehensive care, and this has led to the publication of several clinical
      surveillance guidelines and recommendations for CHARGE syndrome, based on both
      single case observations and cohort studies. Here we perform a structured
      literature review to examine all the existing advice. Our findings provide
      additional support for the validity of the recently published Trider checklist.
      We also identified a gap in literature when reviewing all guidelines and
      recommendations, and we propose a guideline for neuroradiological evaluation of
      patients with CHARGE syndrome. This is of importance, as patients with CHARGE are
      at risk for peri-anesthetic complications, making recurrent imaging procedures
      under anesthesia a particular risk in clinical practice. However, comprehensive
      cranial imaging is also of tremendous value for timely diagnosis, proper
      treatment of symptoms and for further research into CHARGE syndrome. We hope the
      guideline for neuroradiological evaluation will help clinicians provide efficient
      and comprehensive care for individuals with CHARGE syndrome.

PMID- 29168329
TI  - Percutaneous bone-anchored hearing system implant survival after 550 primary
      implant surgeries.

PMID- 29168330
TI  - Web alert: Nitrogen-fixing bacteria: An annotated selection of World Wide Web
      sites relevant to the topics in environmental microbiology.

PMID- 29168327
TI  - Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model
      of CHARGE syndrome.
AB  - Mutations in the gene encoding the ATP dependent chromatin-remodeling factor,
      CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the
      choanae, Retarded growth and development, Genital-urinary anomalies, and Ear
      defects) syndrome. Neurodevelopmental defects and a range of neurological signs
      have been identified in individuals with CHARGE syndrome, including developmental
      delay, lack of coordination, intellectual disability, and autistic traits. We
      previously identified cerebellar vermis hypoplasia and abnormal cerebellar
      foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar
      hypoplasia and distinct cerebellar foliation anomalies in a Chd7
      haploinsufficient mouse model. We describe specific alterations in the precise
      spatio-temporal sequence of fissure formation during perinatal cerebellar
      development responsible for these foliation anomalies. The altered cerebellar
      foliation pattern in Chd7 haploinsufficient mice show some similarities to those
      reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we
      propose that mutations or polymorphisms in these genes may modify the cerebellar
      phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome
      indicate that a careful analysis of cerebellar foliation may be warranted in
      patients with CHARGE syndrome, particularly in patients with cerebellar
      hypoplasia and developmental delay.

PMID- 29168331
TI  - Corrigendum.

PMID- 29168332
TI  - Associative role of HLA-DRB1 SNP genotypes as risk factors for susceptibility and
      severity of rheumatoid arthritis: A North-east Indian population-based study.
AB  - Rheumatoid arthritis (RA) is a complex, multifactorial, systemic autoimmune
      disease. Reports are suggestive of the role of HLA especially HLA-DRB1
      alterations in RA pathogenesis. Existing data involving different geographical
      populations on the role of alterations in specific locus of HLA-DRB1 in RA
      susceptibility and severity are equivocal, with no data available from ethnically
      distinct North-east Indian population, where RA cases are alarmingly increasing.
      This study aimed to evaluate the association of HLA-DRB1 gene SNPs (rs13192471,
      rs660895 and rs6457617) with susceptibility and severity of RA in an ethnically
      distinct North-east Indian population. Whole blood was collected from clinically
      characterized RA cases (satisfying the American College of Rheumatology 1987
      criteria) (n = 123) and community-based age and sex-matched healthy controls (n =
      156) with informed consent. The HLA-DRB1 SNP analysis was performed for all the
      RA and control cases using ARMS-PCR using case and control genomic DNA as
      template. Statistical analysis was performed by SPSSv13.0 software. The HLA-DRB1
      rs660895 showed both wild (AA) and heterozygote (AG) genotype but the
      heterozygote allele was found to be associated with reduced risk of RA compared
      to controls [OR = 0.531, p = .024]. The difference in distribution of rs6457617
      polymorphism between RA and control cases was comparable [OR = 0.525, p = .079].
      Significantly higher distribution of variant rs13192471 genotype was observed in
      RA cases (69.92%) compared to controls (46.75%) (p < .001) and was associated
      with increased risk of susceptibility to RA [OR = 2.576, p < .001] compared to
      controls, as well as progression to severity in RA cases [OR = 2.404, p = .048].
      Combinatorially also, the presence of rs13192471 variant genotype was associated
      with increased risk of RA susceptibility [OR = 8.267, p = .026] and RA severity
      [OR = 3.647, p = .280]. Alterations in HLA-DRB1 are associated with RA
      susceptibility. HLA-DRB1 rs13192471 SNP plays a critical role in RA
      susceptibility and severity in North-east Indian cases and has prognostic
      significance in RA.

PMID- 29168333
TI  - Bladder cancer: diagnosis and management of bladder cancer: (c) NICE (2015)
      Bladder cancer: diagnosis and management of bladder cancer.

PMID- 29168334
TI  - Human development and its impact on genitourinary cancers.

PMID- 29168335
TI  - Prostate cancer biomarkers: new scenarios in the multi-parametric magnetic
      resonance imaging era.

PMID- 29168336
TI  - NICE guidance and the BJUI.

PMID- 29168337
TI  - Novel risk stratification nomograms for counseling patients on the need for
      prostate biopsy.

PMID- 29168338
TI  - Potential new strategies for the treatment of renal medullary carcinoma.

PMID- 29168339
TI  - Prognostic value of PD-L1 expression in combination with CD8+ TILs density in
      patients with surgically resected non-small cell lung cancer.
AB  - To investigate the prognostic value of PD-L1 expression combined with CD8+ TILs
      density in patients with resected NSCLC and correlations with clinicopathological
      features. We retrospectively enrolled 178 patients with resected NSCLC from 2011
      to 2015. All surgical primary and 58 matched metastatic lymph node specimens were
      tested for PD-L1, CD8+ TILs, and oncogenic alterations. PD-L1+ was detected in 71
      (39.9%) and CD8high TILs in 74 (41.6%) cases. Smoking, SqCC, and EGFR- were
      associated with both PD-L1+ and CD8high TILs. Patients with CD8high TILs had
      longer OS (P = 0.012). PD-L1- was significantly associated with longer OS in
      patients with oncogenic alterations (P = 0.047). By multivariate analysis,
      CD8high TILs (HR = 0.411; 95% CI, 0.177-0.954; P = 0.038), rather than PD-L1, was
      the independent predictive factor for OS. The longest and shortest OS were
      achieved in patients with PD-L1+ /CD8high and PD-L1+ /CD8low , respectively (P =
      0.025). Inconsistent PD-L1 expression levels were observed in 23 of 58 (39.7%)
      patients with primary and matched metastatic lymph node specimens. Of them,
      CD8high TILs was significantly associated with longer OS in patients with
      metastatic lymph nodes and/or consistent PD-L1 expression (P = 0.017 and 0.049,
      respectively). The combination of PD-L1 and CD8+ TILs density, instead of PD-L1
      alone, suggested impressive prognostic values in NSCLC patients. Less than half
      of patients with resected NSCLC experienced inconsistent PD-L1 expression between
      primary and metastatic lesions. The level of PD-L1 expression in advanced NSCLC
      needs to be evaluated more comprehensively.

PMID- 29168341
TI  - Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative
      fasting in children.
AB  - BACKGROUND: Children often starve for longer than recommended by current
      preoperative fasting guidelines. AIMS: We studied the effects of implementing a
      more lenient fasting regimen on the duration of clear fluid fasting, as well as
      the incidence of extended fasting in children. METHODS: Preoperative duration of
      clear fluid fasting was recorded for patients scheduled for procedures in a unit
      applying the standard 6-4-2 fasting regimen. This group was compared with a
      cohort in the same unit 1 year after transitioning to a 6-4-0 fasting regimen.
      The latter includes no limitations on clear fluid intake until the child is
      called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen
      has been implemented for over a decade was also studied for comparison. RESULTS:
      Patients fasting according to the 6-4-2 fasting regimen (n = 66) had a median
      fasting time for clear fluids of 4.0 h and a 33.3% incidence of fasting more than
      6 h. After transitioning to the 6-4-0 fasting regimen (n = 64), median duration
      of fasting for clear fluids decreased to 1.0 h, and the incidence of fasting more
      than 6 h decreased to 6.3%. In the second unit (n = 73), median fasting time was
      2.2 h and the proportion of patients fasting more than 6 h was 21.9%. CONCLUSION:
      The introduction and implementation of the 6-4-0 fasting regimen reduces median
      fluid fasting duration and the number of children subjected to extended fasting.

PMID- 29168340
TI  - Hyperoxia induces paracellular leak and alters claudin expression by neonatal
      alveolar epithelial cells.
AB  - BACKGROUND: Premature neonates frequently require oxygen supplementation as a
      therapeutic intervention that, while necessary, also exposes the lung to
      significant oxidant stress. We hypothesized that hyperoxia has a deleterious
      effect on alveolar epithelial barrier function rendering the neonatal lung
      susceptible to injury and/or bronchopulmonary dysplasia (BPD). MATERIALS AND
      METHODS: We examined the effects of exposure to 85% oxygen on neonatal rat
      alveolar barrier function in vitro and in vivo. Whole lung was measured using wet
      to-dry weight ratios and bronchoalveolar lavage protein content and cultured
      primary neonatal alveolar epithelial cells (AECs) were measured using
      transepithelial electrical resistance (TEER) and paracellular flux measurements.
      Expression of claudin-family tight junction proteins, E-cadherin and the Snail
      transcription factor SNAI1 were measured by Q-PCR, immunoblot and confocal
      immunofluorescence microscopy. RESULTS: Cultured neonatal AECs exposed to 85%
      oxygen showed impaired barrier function. This oxygen-induced increase in
      paracellular leak was associated with altered claudin expression, where claudin-3
      and -18 were downregulated at both the mRNA and protein level. Claudin-4 and -5
      mRNA were also decreased, although protein expression of these claudins was
      largely maintained. Lung alveolarization and barrier function in vivo were
      impaired in response to hyperoxia. Oxygen exposure also significantly decreased E
      cadherin expression and induced expression of the SNAI1 transcription factor in
      vivo and in vitro. CONCLUSIONS: These data support a model in which hyperoxia has
      a direct impact on alveolar tight and adherens junctions to impair barrier
      function. Strategies to antagonize the effects of high oxygen on alveolar
      junctions may potentially reverse this deleterious effect.

PMID- 29168342
TI  - Sphingosine-1-phosphate (S1P) enhances glomerular endothelial cells activation
      mediated by anti-myeloperoxidase antibody-positive IgG.
AB  - Cumulating evidences suggested an important role of sphingosine-1-phosphate (S1P)
      and its receptors in regulating endothelial barrier integrity. Our previous study
      revealed that the circulating S1P levels and renal expression of S1PRs correlated
      with disease activity and renal damage in patients with antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study investigated
      the role of S1P and its receptors in myeloperoxidase (MPO)-ANCA-positive IgG
      mediated glomerular endothelial cell (GEnC) activation. The effect of S1P on
      morphological alteration of GEnCs in the presence of MPO-ANCA-positive IgG was
      observed. Permeability assay was performed to determine endothelial monolayer
      activation in quantity. Both membrane-bound and soluble ICAM-1 and VCAM-1 levels
      were measured. Furthermore, antagonists and/or agonists of various S1PRs were
      employed to determine the role of different S1PRs. S1P enhanced MPO-ANCA-positive
      IgG-induced disruption of tight junction and disorganization of cytoskeleton in
      GEnCs. S1P induced further increase in monolayer permeability of GEnC monolayers
      in the presence of MPO-ANCA-positive IgG. S1P enhanced MPO-ANCA-positive IgG
      induced membrane-bound and soluble ICAM-1/VCAM-1 up-regulation of GEnCs. Soluble
      ICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA
      positive IgG increased upon pre-incubation of S1PR1 antagonist, while pre
      incubation of GEnCs with the S1PR1 agonist down-regulated sICAM-1 level. Blocking
      S1PR2-4 reduced sICAM-1 levels in the supernatants of GEnCs stimulated by S1P and
      MPO-ANCA-positive IgG. Pre-incubation with S1PR5 agonist could increase sICAM-1
      level in the supernatants of GEnC stimulated by S1P and MPO-ANCA-positive IgG.
      S1P can enhance MPO-ANCA-positive IgG-mediated GEnC activation through S1PR2-5.

PMID- 29168343
TI  - Lipocalin 2 (Lcn2) interferes with iron uptake by Brucella abortus and dampens
      immunoregulation during infection of RAW 264.7 macrophages.
AB  - Lipocalin 2 (Lcn2) is an important innate immunity component against bacterial
      pathogens. In this study, we report that Lcn2 is induced by Brucella (B.) abortus
      infection and significantly contributes to the restriction of intracellular
      survival of Brucella in macrophages. We found that Lcn2 prevented iron uptake by
      B. abortus through two distinct mechanisms. First, Lcn2 is secreted to capture
      bacterial siderophore(s) and abrogate iron import by Brucella. Second, Lcn2
      decreases the intracellular iron levels during Brucella infection, which probably
      deprives the invading Brucella of the iron source needed for growth. Suppression
      of Lcn2 signalling resulted in a marked induction of anti-inflammatory cytokine,
      interleukin 10, which was shown to play a major role in Lcn2-induced antibrucella
      immunity. Similarly, interleukin 6 was also found to be increased when Lcn2
      signalling is abrogated; however, this induction was thought to be an alternative
      pathway that rescues the cell from infection when the effective Lnc2 pathway is
      repressed. Furthermore, Lcn2 deficiency also caused a marked decrease in
      brucellacidal effectors, such as reactive oxygen species and nitric oxide but not
      the phagolysosome fusion. Taken together, our results indicate that Lcn2 is
      required for the efficient restriction of intracellular B. abortus growth that is
      through limiting iron acquisition and shifting cells to pro-inflammatory
      brucellacidal activity in murine macrophages.

PMID- 29168344
TI  - Animal Embryotoxicity Studies of Key Non-Artemisinin Antimalarials and Use in
      Women in the First Trimester.

PMID- 29168345
TI  - Nonlinear micro-CT based FE modeling of trabecular bone-Sensitivity of apparent
      response to tissue constitutive law and bone volume fraction.
AB  - In this study, the sensitivity of the apparent response of trabecular bone to
      different constitutive models at the tissue level was investigated using finite
      element (FE) modeling based on micro-computed tomography (micro-CT). Trabecular
      bone specimens from porcine femurs were loaded under a uniaxial compression
      experimentally and computationally. The apparent behaviors computed using von
      Mises, Drucker-Prager, and Cast Iron plasticity models were compared. Secondly,
      the effect of bone volume fraction was studied by changing the bone volume
      fraction of a trabecular bone sample while keeping the same basic architecture.
      Also, constitutive models' parameters of the tissue were calibrated for porcine
      bone, and the effects of different parameters on resulting apparent response were
      investigated through a parametric study. The calibrated effective tissue elastic
      modulus of porcine trabecular bone was 10+/-1.2 GPa, which is in the lower range
      of modulus values reported in the literature for human and bovine trabecular
      bones (4-23.8 GPa). It was also observed that, unlike elastic modulus, yield
      properties of tissue could not be uniquely calibrated by fitting an apparent
      response from simulations to experiments under a uniaxial compression. Our
      results demonstrated that using these 3 tissue constitutive models had only a
      slight effect on the apparent response. As expected, there was a significant
      change in the apparent response with varying bone volume fraction. Also, both
      apparent modulus and maximum stress had a linear relation with bone volume
      fraction.

PMID- 29168347
TI  - Erratum.

PMID- 29168348
TI  - Harnessing the power of social media in older adult nursing.

PMID- 29168346
TI  - Cancer-testis gene PIWIL1 promotes cell proliferation, migration, and invasion in
      lung adenocarcinoma.
AB  - Piwi-like RNA-mediated gene silencing 1 (PIWIL1) has been identified as a novel
      extremely highly expressed cancer-testis (CT) gene in lung adenocarcinoma.
      However, the exact function and mechanism of PIWIL1 in lung adenocarcinoma
      remains unclear. Herein, we sought to investigate the role of PIWIL1 in the
      occurrence and development of lung adenocarcinoma. We examined the expression
      pattern of PIWIL1 in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples,
      and validated it by Real-Time PCR (RT-PCR) in additional 21 paired lung
      adenocarcinoma tissues and 16 normal tissues. Subsequently, we explored the
      biological function of PIWIL1 in A549 and H1299 cell lines by gain and loss-of
      function analyses. Using TCGA lung adenocarcinoma data, we further performed
      coexpression and Gene Ontology (GO) analyses, and analyzed the association of DNA
      methylation levels in PIWIL1 promoter region with its expression. Finally, we
      evaluated its expression in different mutation status of significantly mutated
      genes (SMGs) in TCGA lung adenocarcinoma data. We observed that PIWIL1 was
      expressed in testis and lung adenocarcinoma but not in other normal tissues, and
      its high expression was associated with shortened survival of lung cancer
      patients. Overexpression of PIWIL1 could facilitate the proliferation, invasion
      and migration of lung adenocarcinoma cells and vice versa. GO analysis revealed
      that PIWIL1 upregulated genes were enriched in embryonic development, cell
      proliferation and regulation of transcription. Moreover, promoter DNA
      hypomethylation of PIWIL1 could contribute to its aberrant expression in tumors.
      Interestingly, PIWIL1 expression was significantly higher in patients without
      hepatocyte growth factor (HGF) or serine/threonine kinase 11 (STK11) mutation (P
      = 0.006 and 0.005, respectively). PIWIL1 is an epidriver gene in lung
      adenocarcinoma, indicating a potential target for further therapy.

PMID- 29168349
TI  - Bioactive Pimarane Diterpenes from the Arctic Fungus Eutypella sp. D-1.
AB  - Two new pimarane diterpenes, libertellenone M (1) and libertellenone N (2),
      together with five known compounds were isolated from the culture extract of
      Eutypella sp. D-1 derived from high-latitude soil of the Arctic. The structures
      of these compounds were determined by spectroscopic data as well as experimental
      and calculated electronic circular dichroism (ECD) analysis. Antimicrobial and
      cytotoxic activities of the isolated compounds were evaluated. Compound 3
      exhibited weak antibacterial activity against Escherichia coli, Bacillus
      subtilis, and Vibrio vulnificus, each with MIC values of 16 MUg/mL. Compounds 2
      and 3 showed moderate cytotoxic activity against K562 and MCF-7 cell lines with
      IC50 values of 7.67 and 9.57 MUm, respectively.

PMID- 29168352
TI  - Patient satisfaction with information on oral anticancer agent use.
AB  - Adequate information on oral anticancer agent (OACA) use is an essential element
      of optimal cancer care. The present study aimed to get insight into the
      experiences of patients with information on OACA treatment and their
      characteristics regarding information dissatisfaction. Patients of four Dutch
      university hospitals using OACA participated in this observational study and
      completed the Satisfaction with Information about Medicines Scale (SIMS), EORTC
      Quality of Life Questionnaire-C30, Brief Illness Perception Questionnaire, and
      Beliefs about Medicines Questionnaire-Specific. Logistic regression analyses were
      used to determine factors associated with dissatisfaction with information.
      Patients (n = 208) using capecitabine (35%), lenalidomide (15%), imatinib (14%),
      temozolomide (12%), sunitinib (11%), thalidomide (5%), dasatinib (4%), erlotinib
      (2%), and nilotinib (2%) participated. Information on the following SIMS-items
      was inadequate: how OACA elicit their effect, how long it takes before treatment
      works, how to conclude that treatment is effective, the risk of side effects and
      its management, interference with sex life, drowsiness, interference with other
      medication and alcohol and what to do in case of a missed dose. Younger age,
      hematological malignancy, dyspnoea, positive perception of consequences of the
      cancer, low perception of treatment control, and indifferent attitude towards
      OACA were associated with dissatisfaction with information. In conclusion, a
      considerable number of patients would have appreciated receiving more information
      on specific issues relating to the consequences of OACA treatment such as the
      effects and side effects of OACA and the interference of treatment with various
      aspects of their daily life. Oncologists, hematologists, lung-oncologists and
      pharmacists may reconsider the provision of information on OACA treatment.

PMID- 29168351
TI  - Complement 5a-mediated trophoblasts dysfunction is involved in the development of
      pre-eclampsia.
AB  - Pre-eclampsia (PE) is a life-threatening multisystem disorder leading to maternal
      and neonatal mortality and morbidity. Emerging evidence showed that activation of
      the complement system is implicated in the pathological processes of PE. However,
      little is known about the detailed cellular and molecular mechanism of complement
      activation in the development of PE. In this study, we reported that complement
      5a (C5a) plays a pivotal role in aberrant placentation, which is essential for
      the onset of PE. We detected an elevated C5a deposition in macrophages and C5a
      receptor (C5aR) expression in trophoblasts of pre-eclamptic placentas. Further
      study showed that C5a stimulated trophoblasts towards an anti-angiogenic
      phenotype by mediating the imbalance of angiogenic factors such as soluble fms
      like tyrosine kinase 1 (sFlt1) and placental growth factor (PIGF). Additionally,
      C5a inhibited the migration and tube formation of trophoblasts, while, C5aR
      knockdown with siRNA rescued migration and tube formation abilities. We also
      found that maternal C5a serum level was increased in women with PE and was
      positively correlated with maternal blood pressure and arterial stiffness. These
      results demonstrated that the placental C5a/C5aR pathway contributed to the
      development of PE by regulating placental trophoblasts dysfunctions, suggesting
      that C5a may be a novel therapeutic possibility for the disease.

PMID- 29168350
TI  - Breakpoint mapping and haplotype analysis of translocation t(1;12)(q43;q21.1) in
      two apparently independent families with vascular phenotypes.
AB  - BACKGROUND: The risk of serious congenital anomaly for de novo balanced
      translocations is estimated to be at least 6%. We identified two apparently
      independent families with a balanced t(1;12)(q43;q21.1) as an outcome of a
      "Systematic Survey of Balanced Chromosomal Rearrangements in Finns." In the first
      family, carriers (n = 6) manifest with learning problems in childhood, and later
      with unexplained neurological symptoms (chronic headache, balance problems,
      tremor, fatigue) and cerebral infarctions in their 50s. In the second family, two
      carriers suffer from tetralogy of Fallot, one from transient ischemic attack and
      one from migraine. The translocation cosegregates with these vascular phenotypes
      and neurological symptoms. METHODS AND RESULTS: We narrowed down the breakpoint
      regions using mate pair sequencing. We observed conserved haplotypes around the
      breakpoints, pointing out that this translocation has arisen only once. The
      chromosome 1 breakpoint truncates a CHRM3 processed transcript, and is flanked by
      the 5' end of CHRM3 and the 3' end of RYR2. TRHDE, KCNC2, and ATXN7L3B flank the
      chromosome 12 breakpoint. CONCLUSIONS: This study demonstrates a balanced
      t(1;12)(q43;q21.1) with conserved haplotypes on the derived chromosomes. The
      translocation seems to result in vascular phenotype, with or without neurological
      symptoms, in at least two families. We suggest that the translocation influences
      the positional expression of CHRM3, RYR2, TRHDE, KCNC2, and/or ATXN7L3B.

PMID- 29168355
TI  - A novel HLA-A*26 allele, HLA-A*26:01:44, identified in a Caucasian individual.
AB  - HLA-A*26:01:44 differs from HLA-A*26:01:01 by a single substitution in exon 5.

PMID- 29168353
TI  - Genomic risk prediction of aromatase inhibitor-related arthralgia in patients
      with breast cancer using a novel machine-learning algorithm.
AB  - Many breast cancer (BC) patients treated with aromatase inhibitors (AIs) develop
      aromatase inhibitor-related arthralgia (AIA). Candidate gene studies to identify
      AIA risk are limited in scope. We evaluated the potential of a novel analytic
      algorithm (NAA) to predict AIA using germline single nucleotide polymorphisms
      (SNP) data obtained before treatment initiation. Systematic chart review of 700
      AI-treated patients with stage I-III BC identified asymptomatic patients (n = 39)
      and those with clinically significant AIA resulting in AI termination or therapy
      switch (n = 123). Germline DNA was obtained and SNP genotyping performed using
      the Affymetrix UK BioBank Axiom Array to yield 695,277 SNPs. SNP clusters that
      most closely defined AIA risk were discovered using an NAA that sequentially
      combined statistical filtering and a machine-learning algorithm. NCBI PhenGenI
      and Ensemble databases defined gene attribution of the most discriminating SNPs.
      Phenotype, pathway, and ontologic analyses assessed functional and mechanistic
      validity. Demographics were similar in cases and controls. A cluster of 70 SNPs,
      correlating to 57 genes, was identified. This SNP group predicted AIA occurrence
      with a maximum accuracy of 75.93%. Strong associations with arthralgia, breast
      cancer, and estrogen phenotypes were seen in 19/57 genes (33%) and were
      functionally consistent. Using a NAA, we identified a 70 SNP cluster that
      predicted AIA risk with fair accuracy. Phenotype, functional, and pathway
      analysis of attributed genes was consistent with clinical phenotypes. This study
      is the first to link a specific SNP/gene cluster to AIA risk independent of
      candidate gene bias.

PMID- 29168356
TI  - Single institution experience on cancer among adolescents 15-19 years of age.
AB  - Yagci-Kupeli B, Akyuz C, Yalcin B, Varan A, Kutluk T, Buyukpamukcu M. Single
      institution experience on cancer among adolescents 15-19 years of age. Turk J
      Pediatr 2017; 59: 1-5. Adolescent cancers differ from other age groups in terms
      of cancer types, treatment and outcome. We aimed to present our institutional
      data on survival of certain types of cancer in adolescents. Hospital files were
      retrospectively evaluated for distribution of tumor types, clinical features, and
      overall and event-free survival (OS and EFS) rates in adolescents with malignant
      tumors. Two hundred ninety-three cases between 15-19 years who were diagnosed
      with malignant tumor at our department in the last 38 years were included in the
      study. Mean age was 15.3 and median age was 15 years at time of diagnosis.
      Male/female ratio was found to be 1.8/1. The most common cancers were non-Hodgkin
      lymphoma (NHL) (20.5%), Hodgkin's lymphoma (HL) (19.8%), central nervous system
      (CNS) tumors (10.9%), osteosarcoma (10.6%), Ewing sarcoma/primitive
      neuroectodermal tumors (EWN/PNET (9.9%) nasopharyngeal carcinoma (NPC) (9.6%).
      Non-compliance to medical treatment was observed in 10.9% of cases with
      significantly high non-compliance in NHL and osteosarcoma (p=0.02). Overall
      survival was 57.6% and EFS was 45.7% at a median follow-up time of 8.75 years. In
      adolescents, lower OS and EFS rates than the younger age group are observed. The
      most appropriate management plan should be made according to the physical and
      psychosocial needs of patients in this age group.

PMID- 29168357
TI  - Predictors of methotrexate response in Turkish children with oligoarticular and
      polyarticular juvenile idiopathic arthritis.
AB  - Batu ED, Sonmez HE, Gulhan B, Arici ZS, Topaloglu R, Bilginer Y. Predictors of
      methotrexate response in Turkish children with oligoarticular and polyarticular
      juvenile idiopathic arthritis. Turk J Pediatr 2017; 59: 6-12. Methotrexate (MTX)
      is the most commonly used disease modifying anti-rheumatic drug in juvenile
      idiopathic arthritis (JIA). We aimed to define predictor factors for response to
      MTX in Turkish children with oligo- and polyarticular JIA. We reviewed the
      medical files of 59 oligo- and 57 polyarticular JIA patients seen in the clinic
      between May 2008 and May 2013 and who received MTX for >=6 months. MTX responders
      were defined as having no/low disease activity according to juvenile arthritis
      disease activity score 71 (JADAS71) at 6 months after MTX initiation. Median age
      at JIA diagnosis/MTX initiation was 70/78 months. Involvement of the small or
      upper extremity joints at disease diagnosis and MTX initiation was more frequent;
      antinuclear antibody (ANA) positivity was less frequent; acute phase reactants,
      JADAS71 at MTX initiation, and the frequency of polyarticular subtype were higher
      in MTX non-responders. In multiple logistic regression, oligoarticular JIA
      subtype and ANA positivity were independent predictors of MTX response.

PMID- 29168359
TI  - The effects of routine administration of probiotics on the length of central
      venous line usage in extremely premature infants.
AB  - Rajput N, Filipovska J, Hewson M. The effects of routine administration of
      probiotics on the length of central venous line usage in extremely premature
      infants. Turk J Pediatr 2017; 59: 20-27. The objective of this study was to
      determine whether the routine use of probiotics was associated with earlier
      removal of peripherally inserted central catheter (PICC) lines in extremely
      premature infants born <=28 weeks' gestation. This study was a retrospective,
      observational, cohort study in infants born <=28 weeks gestation in the 2 years
      before [No Probiotic Group (NPG)] and after [Probiotic Group (PG)] the
      commencement of the routine use of probiotics (lnfloran(r)) in a large tertiary
      neonatal intensive care unit in the North Island of New Zealand. Age at the
      removal of PICC line in patients whose first PICC lines were inserted before day
      14 and remained in-situ for at least 4 days was compared using Kaplan-Meir
      Survival Analysis on SPSS 22.0(r). We studied PICC line infections as a secondary
      outcome measure. We compared 120 PICC lines in NPG and 130 PICC lines in PG. Mean
      age at removal was 25.9 [(95% Confidence Intervals (CI)=22.6 - 29.2)] days in NPG
      and 23.1 (95% CI=20.9 - 25.2) days in PG. The result was independent of birth
      weight, gender, type of PICC line and age at insertion but related significantly
      to gestation at birth (p < 0.001). There was no difference in the incidence or
      the microbiologic profile of PICC line infections between the study groups. PICC
      lines were removed 2.8 days earlier in infants receiving probiotics (p=0.070),
      which can have potential benefits with reduced infection and other risks due to
      earlier removal of PICC lines.

PMID- 29168358
TI  - The effect of early administration of combined multi-strain and multi-species
      probiotics on gastrointestinal morbidities and mortality in preterm infants: A
      randomized controlled trial in a tertiary care unit.
AB  - Guney-Varal I, Koksal N, Ozkan H, Bagci O, Dogan P. The effect of early
      administration of combined multi-strain and multi-species probiotics on
      gastrointestinal morbidities and mortality in preterm infants: A randomized
      controlled trial in a tertiary care unit. Turk J Pediatr 2017; 59: 13-19.
      Necrotizing enterocolitis (NEC) is a gastrointestinal emergency of the neonatal
      period. The aim of this study was to demonstrate the use of multistrain and
      multispecies probiotic on gastrointestinal morbidities and mortality. The study
      was organized as a randomized controlled, prospective study in premature infants
      (<=32 week and <=1500 gram). The ready commercial preparations which contain
      multi-combined probiotics of Lactobacillus rhamnosus (4.1x108 cfu) +
      Lactobacillus casei (8.2x108 cfu) + Lactobacillus plantorum (4.1x108 cfu) +
      Bifidobacterium animalis (4.1x108 cfu) together with 383 mg of
      fructooligosaccharides and 100 mg of galactooligosaccharides as the prebiotic
      content, was administered enterally to the probiotic group (n=70); control group
      constituted of 40 preterms. Primary outcomes of the present study were >= Stage 2
      NEC and the mortality. Secondary outcomes were culture-proven sepsis and days to
      reach full enteral feeding. All cases of NEC were seen in group 2 as 3.6% (n=4)
      of all infants. The mortality was found to be 1.4% (n=1) in Group 1 and 22.5%
      (n=9) in Group 2. The incidence of NEC and the mortality rate were found to be
      significantly lower in Group 1 (p=0.016, p=0.001, respectively). In Group 1, the
      NEC-related mortality rate and sepsis-related mortality rate were significantly
      lower than that of the control group (p=0.046, p=0.023). In this study, we showed
      that using probiotic strains in combined multistrain and multispecies forms at
      higher doses and for prolonged duration had positive effects on gastrointestinal
      complications, sepsis and mortality in premature infants.

PMID- 29168360
TI  - Does Nissen fundoplication improve deglutition in children?
AB  - Soyer T, Yalcin S, Demir N, Karhan AN, Saltik-Temizel IN, Demir H, Tanyel FC.
      Does Nissen fundoplication improve deglutition in children? Turk J Pediatr 2017;
      59: 28-34. A prospective study was performed to evaluate the effect of Nissen
      fundoplication (NF) on deglutition in children. Children who underwent NF between
      2011-2015 were evaluated for demographic features, clinical findings, diagnostic
      methods for gastroesophageal reflux (GER) and indications for NF. Penetration
      aspiration scale (PAS), functional oral intake scale (FOIS) and esophageal
      functions were evaluated by videoflouroscopy (VFS). Preoperative and
      postoperative VFS findings were compared to evaluate the effect of NF on clinical
      findings and deglutition. Twenty-three children with a mean age of 5.08 +/- 3.7
      years were included. Female to male ratio was 15:8. Recurrent respiratory
      infections (RTI) (n: 14, 60.8%), swallowing dysfunction (n:13, 56.5%) and
      vomiting (n:10, 43.4%) were the most common symptoms. Preoperatively GER was
      diagnosed with barium swallowing study (BSS) contrast graphs (n:20, 87%) and with
      24-hour esophageal pH monitorization (n:8, 34.8%). In 39.1% of patients, medical
      treatment for GER was used with a mean duration of 8 +/- 5.8 months. Indications
      for NF were swallowing dysfunction (n: 18, 78%), GER complications (n:6, 26%),
      associated anatomical problems (n:4, 17.3%) and unresponsiveness to medical
      treatment (n: 3, 13%). Postoperative barium swallowing study and 24-hour
      esophageal pH monitorization showed no GER after NF in 95% of patients. Number of
      RTI were significantly decreased after NF (preoperative vs postoperative
      infection rate 4.21 vs 1.6 respectively, p < 0.05). VFS findings showed that PAS
      was significantly decreased after NF during both liquid and semi-liquid
      swallowing (p < 0.05). After NF, upper esophageal opening (UEO) was decreased
      when compared to preoperative VFS findings (p < 0.05 Esophageal cleaning,
      esophageal motility, esophageal backflow and lower esophageal sphincter narrowing
      did not alter after NF (p > 0.05). FOIS were significantly improved after NF (p <
      0.05). VFS findings showed that penetration and aspiration were significantly
      decreased after NF and children had less RTI. Although, esophageal motility
      evaluated by VFS did not changed after NF, functional oral intake significantly
      improved in children.

PMID- 29168361
TI  - Hypophosphatemia associated risk factors in pediatric intensive care patients.
AB  - San ES, Erdogan S, Bosnak M, San M. Hypophosphatemia associated risk factors in
      pediatric intensive care patients. Turk J Pediatr 2017; 59: 35-41. The aim of
      this work is to determine the prevalence and risk factors of hypophosphatemia in
      pediatric patients admitted to intensive care unit. The study was performed
      prospectively in patients admitted to the Pediatric Intensive Care Unit between
      June 2014 and December 2014. Fifty-seven patients were included in the study. The
      mean age of the study population was 24 months (2-192 months); 25 patients
      (43.9%) were male and 32 were female (56.1%). The mean body weight z-score was 
      1.47 +/- 2.23, and 23 (40.4%) patients had malnutrition. On admission 16 (28.1%)
      patients had hypophosphatemia. There were no statistically significant
      differences between the hypophosphatemic patient group and normophosphatemic
      patient groups in terms of demographic and clinical characteristics. There were
      also no significant differences between the two groups in terms of risk factors.
      Potassium and creatinine levels were significantly lower in the hypophosphatemic
      group, compared to the normophosphatemic group. According to a multivariate
      logistic regression analysis, risk factors for hypophosphatemia were low
      potassium level (OR: 16.76; 95% CI: 2.09 - 134.72; p: 0.008), malignant solid
      tumors (OR: 52.40; 95% CI: 2.04 - 1,344.32; p: 0.017, p: 0.036). and female
      gender (OR: 6.18; 95% CI: 1.12 - 34.00; p: 0.036). Prospective studies with
      larger sample size should be conducted to study the prevalence and risk factors
      of hypophosphatemia at pediatric intensive care unit.

PMID- 29168362
TI  - The evaluation of right and left ventricular functions in children with episodic
      wheezing exposed to environmental tobacco smoke.
AB  - Doksoz O, Nacaroglu HT, Ceylan G, Celegen M, Asik-Nacaroglu S, Can D, Mese T,
      Unal N. The evaluation of right and left ventricular functions in children with
      episodic wheezing exposed to environmental tobacco smoke. Turk J Pediatr 2017;
      59: 42-48. The objective of this study is to examine the right and left
      ventricular functions in children with episodic wheezing at the ages of 1-3
      exposed to environmental tobacco smoke (ETS). Thirty-two children monitored at
      the Pediatric Allergy and Immunology Department of a Research and Training
      Hospital with the diagnosis of episodic wheezing were included. The prospective
      assessment of the patients was performed between May 2013 and February 2014.
      Twenty-five children with episodic wheezing not exposed to ETS formed the control
      group. The two groups were compared by conducting transthoracic two-dimensional
      and tissue Doppler echocardiography (TDE) examination in all of the cases. The
      average age of the study group (24 boys, 8 girls) was 33.1 +/- 8.8 months, the
      average age of the control group (18 boys, 7 girls) was 31.9 +/- 11.9 months.
      There was no statistically significant difference between the two groups in terms
      of age, gender, weight, height, and body mass index values. There was no
      statistically significant difference between the two groups for the right and
      left ventricular systolic and diastolic functions in the conventional
      echocardiographic measurements, and for the measurements of TDE. Limited number
      of patients is a major limitation of the study. These results should be supported
      by more comprehensive studies.

PMID- 29168363
TI  - Free estradiol index levels associated with high sensitivity CRP levels in male
      children.
AB  - Agirbasli M, Tanrikulu A, Azizy M. Free estradiol index levels associated with
      high sensitivitiy CRP levels in male children. Turk J Pediatr 2017; 59: 49-55.
      Biomarkers of inflammation such as high-sensitivity C-reactive protein (hs-CRP)
      associate with subclinical atherosclerosis. Atherosclerosis is an early onset
      disease in life. Sex hormones and puberty modulate metabolism in children.
      Studies indicate that low sex hormone binding globulin (SHBG) levels associate
      with insulin resistance and metabolic syndrome in children. The aim of this study
      is to study the correlation between sex hormones and hs-CRP levels in children
      and adolescents. The study sample was derived from a cross sectional survey on
      the prevalence of cardiovascular risk factors in a representative sample of
      school children (8-17 year-old) in Istanbul, Turkey. In addition to
      anthropometric and biochemical characteristics of cardiovascular risk, sex
      hormones such as free androgen index, free estradiol index (FEI), SHBG and hs-CRP
      levels were measured in all study participants: 91 boys (12.4 +/- 3.4 years) and
      77 girls (12.7 +/- 3.4 years) were included in the study. Median (interquartile
      range) hs-CRP levels were similar among boys and girls [0.36 (0.9) versus 0.45
      (0.7) mg/dl, p= 0.725]. Gender stratified analysis displayed that hs-CRP levels
      positively correlated with FEI levels (r=0.438, p < 0.001) in boys. Linear
      regression analysis was performed to determine the predictors of hs-CRP. Among
      covariates of FEI, homeostasis model assessment-estimated insulin resistance,
      body mass index, age, and SHBG; FEI was shown to significantly and independently
      predict hs-CRP levels in boys [beta=2.758, p < 0.001, 95% confidence interval
      (CI) for beta 1.471-4.045]. FEI levels associate with subclinical inflammation in
      boys. Future studies may elucidate the role of sex hormone levels in inflammation
      among children.

PMID- 29168364
TI  - Aggressive periodontitis associated with Kindler syndrome in a large Kindler
      syndrome pedigree.
AB  - Talo-Yildirim T, Acun-Kaya F, Taskesen M, Dundar S, Bozoglan A, Tekin GG, Akdeniz
      S. Aggressive periodontitis associated with Kindler syndrome in a large Kindler
      syndrome pedigree. Turk J Pediatr 2017; 59: 56-61. Kindler syndrome (KS) is a
      rare genetic disorder. The clinical features include aggressive periodontal
      disease and severe desquamative gingivitis. Five individuals with KS were
      assessed by oral examination, radiographic analysis and periodontal measurements.
      All the patients' indexes were recorded prior to periodontal treatment and at the
      end of the 1th, 3th , 6th, 9th and 12th month respectively. All the patients had
      improvement of periodontal status and enhancement in index scores. The affected
      individuals were previously screened for FERMT1 mutations. KS patients'
      periodontal disease activity could be taken under control with regular follow-up.

PMID- 29168365
TI  - Evaluation of choroidal thickness measurements in pediatric obstructive sleep
      apnea syndrome patients.
AB  - Bayraktar C, Simsek A. Evaluation of choroidal thickness measurements in
      pediatric obstructive sleep apnea syndrome patients. Turk J Pediatr 2017; 59: 62
      67. Choroidal vascular impairment and obstructive sleep apnea syndrome (OSAS)
      related disorders have been shown in adults, but there have been no
      investigations with regard to the choroidal thickness measurements in children
      with OSAS. Our aim was to investigate this relationship in the early childhood
      period, which correlates with OSAS peak incidence due to adenotonsillar
      enlargement. One-hundred and nine pediatric OSAS patients and 42 age-sex matched
      controls were enrolled in this study. Nocturnal pulse oximetry was used to define
      the OSAS patients. Demographic data like age, sex and body-mass index were
      recorded. All of the subjects underwent complete otolaryngologic and
      ophthalmologic examination including visual acuity, intraocular pressure, central
      corneal thickness, axial length and choroidal thickness measurements. Overall,
      the 1,000 MUm and 1,500 MUm nasal choroid measurements were found to be
      significantly lower in the patient group (p < 0.05). However, only a poor inverse
      correlation emerged between the body-mass index (BMI) and the foveal center
      measurements in the patients. Observed alterations in the choroid may signify the
      initial impairment of known OSAS-related eye disorders, like glaucoma, floppy
      eyelid syndrome, and non-arteritic ischemic optic neuropathy. Ophthalmologists,
      otolaryngologists and pediatricians working together as a team may be able to
      prevent future eye diseases.

PMID- 29168366
TI  - Normal sweat chloride test does not rule out cystic fibrosis.
AB  - Basaran AE, Karatas-Torun N, Maslak IC, Bingol A, Alper OM. Normal sweat chloride
      test does not rule out cystic fibrosis. Turk J Pediatr 2017; 59: 68-70. A 5-month
      old patient presented with complaints of fever and cough. He was hospitalized
      with the diagnosis of bronchopneumonia and pseudo-Bartter's syndrome. Patient was
      further investigated for diagnosis of cystic fibrosis. The chloride (Cl) level in
      sweat was determined within the normal range (25.1 mmol/L, 20.3 mmol/L). CFTR
      (Cystic Fibrosis Transmembrane Regulator gene; NM_000492.2) genotyping results
      were positive for p.E92K; p.F1052V mutations. The patient was diagnosed with
      cystic fibrosis. In our patient, with features of CF and normal sweat test,
      mutation analysis was helpful for the diagnosis of cystic fibrosis.

PMID- 29168367
TI  - Neonatal cerebral sinovenous thrombosis: Two cases, two different gene
      polymorphisms and risk factors.
AB  - Turan O, Anuk-Ince D, Olcay L, Sezer T, Gulleroglu K, Yilmaz-Celik Z, Ecevit A.
      Neonatal cerebral sinovenous thrombosis: Two cases, two different gene
      polymorphisms and risk factors. Turk J Pediatr 2017; 59: 71-75. Cerebral
      sinovenous thrombosis (CSVT) is a rare disease in the neonatal period and also
      the greatest risk of neonatal mortality and morbidity. In this report, we
      presented two cases with CSVT and different risk factors. One of these cases had
      methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism and the
      other case had both MTHFR A1298C homozygous polymorphism, plasminogen activator
      inhibitor-1 (PAI-1) 4G/ 5G polymorphism and elevated lipoprotein a. Early
      diagnosis and prompt initiation of therapy of neonatal CSVT may prevent neonatal
      mortality and poor long-term neurodevelopmental outcomes.

PMID- 29168368
TI  - A congenital soft tissue Ewing sarcoma in a newborn patient.
AB  - Akcali M, Yapicioglu H, Akay E, Ozlu F, Kozanoglu B, Erdogan K, Gonlusen G, Satar
      M. A congenital soft tissue Ewing sarcoma in a newborn patient. Turk J Pediatr
      2017; 59: 76-79. < p < Congenital Ewing sarcoma is extremely rare. Here we
      present a newborn baby born with a mass on the left shoulder. Immunohistochemical
      staining showed congenital Ewing sarcoma. Chemotherapy and then surgical
      operation were planned, however the patient died before initiation of
      chemotherapy on the 30th day of life.

PMID- 29168369
TI  - Polyposis deserves a perfect physical examination for final diagnosis: Bannayan
      Riley-Ruvalcaba syndrome.
AB  - Hizarcioglu-Gulsen H, Kilic E, Dominguez-Garrido E, Aydemir Y, Utine GE, Saltik
      Temizel IN. Polyposis deserves a perfect physical examination for final
      diagnosis: Bannayan-Riley-Ruvalcaba syndrome. Turk J Pediatr 2017; 59: 80-83.
      Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare autosomal dominant inherited
      polyposis syndrome characterized by macrocephaly, lipomatosis, hemangiomatosis,
      intestinal polyposis and pigmented macules on penis. The mutation of the PTEN
      gene that is responsible for controlling cellular proliferation, migration and
      apoptosis clarifies the reason of tissue overgrowth in BRRS. Gastrointestinal
      tract involvement is seen 35-45% of the patients. Histologic features of polyps
      in BRRS resemble juvenile polyps. In this report, we describe a boy presenting
      with hematochezia and aggressive polyposis and finally was diagnosed as BRRS due
      to extra intestinal findings.

PMID- 29168370
TI  - Two cases of Kawasaki disease presented with acute febrile jaundice.
AB  - Kawasaki disease is an acute, systemic vasculitis of unknown etiology. Although
      gastrointestinal involvement does not belong to the classic diagnostic criteria;
      diarrhea, abdominal pain, hepatic dysfunction, hydrops of gallbladder, and acute
      febrile cholestatic jaundice are reported in patients with Kawasaki disease. We
      describe here two cases presented with fever, and acute jaundice as initial
      features of Kawasaki disease.

PMID- 29168371
TI  - Congenital insensitivity to pain: How should anesthesia be managed?
AB  - Ozmete O, Sener M, Bali C, Caliskan E, Aribogan A. Congenital insensitivity to
      pain: How should anesthesia be managed? Turk J Pediatr 2017; 59: 87-89.
      Congenital insensitivity to pain syndrome is a rare, sensorial and autonomic
      neuropathy characterized by unexplained fever, insensitivity to pain and
      anhidrosis. Patients may require anesthesia even for minor surgical procedures
      due to mental retardation and trauma arising from self- mutilating behavior. A
      child diagnosed with congenital insensitivity to pain syndrome was scheduled for
      gastric endoscopy under sedation due to suspected ingestion of a household
      cleaning disinfectant. Deep sedation was achieved, and spontaneous respiration
      was maintained. We did not encounter any complications. There is limited data
      regarding the safe anesthesia management in these patients because of the rarity
      of the disease. Therefore, we think that more clinical experience, case reports
      and studies are needed to establish the appropriate anesthesia management.

PMID- 29168372
TI  - Tuba-ovarian auto-amputation caused by ovarian teratoma in an adolescent girl.
AB  - Atici A, Yilmaz E, Karaman A, Apaydin S, Afsarlar CE. Tuba-ovarian auto
      amputation caused by ovarian teratoma in an adolescent girl. Turk J Pediatr 2017;
      59: 90-92. Ovarian auto-amputation is an extremely rare condition commonly
      encountered in the perinatal period. Spontaneous or secondary torsion of the
      ovary caused by an ovarian lesion may result in infarction and subsequent auto
      amputation of the ovary. This paper demonstrates a case that underwent
      laparoscopic appendectomy with an incidental calcified auto-amputated right
      ovary. A 16-year-old adolescent girl was admitted to our department with a
      history of one-day abdominal pain. Physical examination of the patient revealed
      abdominal tenderness and rigidity on right lower quadrant. Her white blood cell
      count was 11x103/mL, and C-reactive protein was 69 mg/L. The patient underwent a
      laparoscopic appendectomy with a provisional diagnosis of acute appendicitis, and
      further exploration revealed a 2x2 cm white ovoid mass floating freely in the
      pelvis. The left ovary was clearly identified in its usual localization, but the
      right tuba was blindly ending without any fimbria or ovary. Postoperative course
      of the patient was uneventful, and she was discharged on postoperative day 2. The
      histopathological examination revealed a necrotic calcified ovarian teratoma.
      Auto-amputated ovary is a rare occasion mostly encountered during perinatal
      period, and it may be unilateral or bilateral. An auto-amputated ovarian mass may
      rarely be a teratoma although the most common cause of auto-amputation during
      perinatal and adolescent period is ovarian torsion due to an ovarian cyst.

PMID- 29168373
TI  - Kocuria kristinae-caused sepsis in an infant with congenital tufting enteropathy.
AB  - Aydin M, Ganschow R, Jankofsky M. Kocuria kristinae-caused sepsis in an infant
      with congenital tufting enteropathy. Turk J Pediatr 2017; 59: 93-96. Congenital
      tufting enteropathy (CTE) is characterized by the early-onset of chronic diarrhea
      and the inability to develop. It is a rare congenital disease with a low
      prevalence of 1:50,000 - 100,000 live births p.a. The histopathology is
      characterized by villous atrophy and the characteristic epithelial tufts. Recent
      identification of causative mutations in EpCAM has enhanced our understanding of
      this disease. Due to its severe clinical course, patients are dependent on
      parenteral nutrition to thrive successfully. Catheter-associated blood stream
      infections have become the primary problem for pediatric patients. Infections
      with Kocuria kristinae are rare. This report is about a 3-month-old girl with CTE
      suffering from a central venous catheter related mono-sepsis by K. kristinae. A
      sepsis therapy with meropenem and vancomycin improved her general state rapidly.
      Only few cases in the literature with CTE and K. kristinae are described. To the
      best of our knowledge, this is the first report presenting two coincidences in
      one case.

PMID- 29168374
TI  - Foreign body punctured the spleen: An incidental diagnosis.
AB  - Inal-Aslan G, Otgun I, Guney LH, Hicsonmez A. Foreign body punctured the spleen:
      An incidental diagnosis. Turk J Pediatr 2017; 59: 97-99. A foreign body can enter
      the body via penetration through the skin. In the presented case, a broken
      syringe needle was found and removed from the splenic parenchyma. In order to
      prevent such iatrogenic injuries, which could have fatal consequences, the
      hospital staff must give particular care in the handling of sharp FBs.

PMID- 29168375
TI  - Cholestasis and hypercalcemia secondary to panhypopituitarism in a newborn.
AB  - Dursun F, Gerenli N, Kirmizibekmez H. Cholestasis and hypercalcemia secondary to
      panhypopituitarism in a newborn. Turk J Pediatr 2017; 59: 100-103. Cholestatic
      hepatitis and hypercalcemia are rare features of hypopituitarism in newborns. So
      diagnosis of hypopituitarism is frequently delayed. The most frequent symptoms of
      congenital hypopituitarism are hypoglycemia, prolonged jaundince and micropenis.
      A patient with congenital hypopituitarism associated with cholestasis and
      hypercalcemia is reported here. Newborns with hypercalcemia and cholestasis
      should alert pediatricians to the possibility of congenital hypopituitarism and
      prompt endocrinological investigation.

PMID- 29168377
TI  - Universal Porphyrinic Metal-Organic Framework Coating to Various Nanostructures
      for Functional Integration.
AB  - A universal strategy was reported that enables functional group-capped
      nanostructures with various morphologies and compositions to be coated by
      porphyrin metal-organic framework (MOF). Based on the nanostructure-induced
      heterogeneous nucleation, the controlled growth of MOF shell on the surface of
      nanostructures can be realized. It was demonstrated that this modification
      strategy can realize controlled growth of porphyrin MOF on a series of organic
      and inorganic nanostructures, such as polydopamine (PDA) nanoparticles, PDA@Pt
      nanoparticles, graphene oxide sheets, and Au nanorods. The as-prepared composites
      exhibit excellent catalytic and optical properties that originate from the
      nanostructure as well as the coated porphyrin MOF. We further explored the
      potential applications of PDA@MOF and PDA@Pt@MOF in nanomedicine and
      photocatalysis.

PMID- 29168376
TI  - Tuning the Flexibility of Glycine-Serine Linkers To Allow Rational Design of
      Multidomain Proteins.
AB  - Flexible polypeptide linkers composed of glycine and serine are important
      components of engineered multidomain proteins. We have previously shown that the
      conformational properties of Gly-Gly-Ser repeat linkers can be quantitatively
      understood by comparing experimentally determined Forster resonance energy
      transfer (FRET) efficiencies of ECFP-linker-EYFP proteins to theoretical FRET
      efficiencies calculated using wormlike chain and Gaussian chain models. Here we
      extend this analysis to include linkers with different glycine contents. We
      determined the FRET efficiencies of ECFP-linker-EYFP proteins with linkers
      ranging in length from 25 to 73 amino acids and with glycine contents of 33.3%
      (GSSGSS), 16.7% (GSSSSSS), and 0% (SSSSSSS). The FRET efficiency decreased with
      an increasing linker length and was overall lower for linkers with less glycine.
      Modeling the linkers using the WLC model revealed that the experimentally
      observed FRET efficiencies were consistent with persistence lengths of 4.5, 4.8,
      and 6.2 A for the GSSGSS, GSSSSS, and SSSSSS linkers, respectively. The observed
      increase in linker stiffness with reduced glycine content is much less pronounced
      than that predicted by a classical model developed by Flory and co-workers. We
      discuss possible reasons for this discrepancy as well as implications for using
      the stiffer linkers to control the effective concentrations of connected domains
      in engineered multidomain proteins.

PMID- 29168378
TI  - Molar Range Detection Based on Sideband Differential Absorption Spectroscopy with
      a Concentrated Reference.
AB  - Conventional absorption spectroscopy (CAS) with a blank reference has only a
      slight capacity to detect high concentrations at characteristic wavelengths owing
      to the corresponding large molar absorption coefficient (epsilon) on the scale of
      103 or 104 cm-1 M-1. To monitor concentrated analytes as high as the molar range
      in a plating bath and on a chemical production line, we propose a new approach
      using sideband differential absorption spectroscopy (SDAS). SDAS is obtained by
      subtracting the absorption spectra of the samples, A(lambda,Cx), from that of a
      reference containing a concentrated standard analyte, A(lambda,Cref>Cx),
      resulting in concave spectra with peaks at the sideband of conventional spectra
      with generally low epsilon values on the scale of 100 cm-1 M-1 or less. The
      negative absorbance changes linearly with the sample concentration at a certain
      peak wavelength, obeying Lambert-Beer's law. In this work, SDAS was obtained and
      verified using inorganic and organic substances, such as chromate potassium,
      rhodamine B, and paracetamol.

PMID- 29168379
TI  - Autonomously Self-Adhesive Hydrogels as Building Blocks for Additive
      Manufacturing.
AB  - We report a simple method of preparing autonomous and rapid self-adhesive
      hydrogels and their use as building blocks for additive manufacturing of
      functional tissue scaffolds. Dynamic cross-linking between 2-aminophenylboronic
      acid-functionalized hyaluronic acid and poly(vinyl alcohol) yields hydrogels that
      recover their mechanical integrity within 1 min after cutting or shear under both
      neutral and acidic pH conditions. Incorporation of this hydrogel in an
      interpenetrating calcium-alginate network results in an interfacially stiffer but
      still rapidly self-adhesive hydrogel that can be assembled into hollow perfusion
      channels by simple contact additive manufacturing within minutes. Such channels
      withstand fluid perfusion while retaining their dimensions and support
      endothelial cell growth and proliferation, providing a simple and modular route
      to produce customized cell scaffolds.

PMID- 29168380
TI  - Quantitative Study of the Oligomerization of Yeast Prion Sup35NM Proteins.
AB  - The fibrillation of misfolded neurodegenerative disease-related proteins has been
      extensively studied over the past few decades, but the initial oligomerization
      has been rarely examined even though some recent evidence indicated that small
      protein oligomers are more neurotoxic than long protein fibers. It is rather
      difficult to study the initial oligomerization (nucleation) because most
      experimental methods, such as the beta-sheet-related fluorescence assay and X-ray
      diffraction, are unable to detect small structureless protein oligomers. In this
      study, we have successfully developed a method to link a short thermally
      sensitive poly(N-isopropylacrylamide) (PNIPAM) chain to a model protein, Sup35NM,
      at a specific 31st residue site (Sup35NM-31m-PNIPAM) via the efficient thiol-ene
      Michael addition reaction. The oligomerization was studied by a combination of
      laser light scattering, the thioflavin T assay, and transmission electron
      microscopy. We found that the lag phase of Sup35NM was delayed from 12 to >24 h
      under the physiological condition after the PNIPAM linkage. The oligomerization
      and fibrillation constants decreased from 5.0 * 10-3 to 1.5 * 10-3 h-1 and from
      3.0 * 10-2 to 1.8 * 10-2 MUM-1 h-1, respectively, presumably because of the
      steric hindrance introduced by the PNIPAM chain. Moreover, after initiating the
      oligomerization, we found that the oligomer distribution in the first 6 h
      repeatedly and quantitatively follows the Smoluchowski coagulation model. Our
      study paves the way for controllably and quantitatively studying the
      oligomerization kinetics of amyloidogenic proteins. In addition, by investigating
      the effects of different small molecules on the oligomerization kinetics, we
      should be able to screen potential drugs to slow the development of
      neurodegenerative diseases.

PMID- 29168381
TI  - Cellular Biosensors with Engineered Genetic Circuits.
AB  - An increasing interest in building novel biological devices with designed
      cellular functionalities has triggered the search of innovative tools for
      biocomputation. Utilizing the tools of synthetic biology, numerous genetic
      circuits have been implemented such as engineered logic operation in analog and
      digital circuits. Whole cell biosensors are widely used biological devices that
      employ several biocomputation tools to program cells for desired functions. Up to
      the present date, a wide range of whole-cell biosensors have been designed and
      implemented for disease theranostics, biomedical applications, and environmental
      monitoring. In this review, we investigated the recent developments in
      biocomputation tools such as analog, digital, and mix circuits, logic gates,
      switches, and state machines. Additionally, we stated the novel applications of
      biological devices with computing functionalities for diagnosis and therapy of
      various diseases such as infections, cancer, or metabolic diseases, as well as
      the detection of environmental pollutants such as heavy metals or organic toxic
      compounds. Current whole-cell biosensors are innovative alternatives to classical
      biosensors; however, there is still a need to advance decision making
      capabilities by developing novel biocomputing devices.

PMID- 29168382
TI  - Comparative Proteomic Analysis of Lysine Acetylation in Trypanosomes.
AB  - Protein acetylation is a post-translational modification regulating diverse
      cellular processes. By using proteomic approaches, we identified N-terminal and
      epsilon-lysine acetylated proteins in Trypanosoma cruzi and Trypanosoma brucei,
      which are protozoan parasites that cause significant human and animal diseases.
      We detected 288 lysine acetylation sites in 210 proteins of procyclic form, an
      insect stage of T. brucei, and 380 acetylation sites in 285 proteins in the form
      of the parasite that replicates in mammalian bloodstream. In T. cruzi insect
      proliferative form we found 389 epsilon-lysine-acetylated sites in 235 proteins.
      Notably, we found distinct acetylation profiles according to the developmental
      stage and species, with only 44 common proteins between T. brucei stages and 18
      in common between the two species. While K-ac proteins from T. cruzi are enriched
      in enzymes involved in oxidation/reduction balance, required for the parasite
      survival in the host, in T. brucei, most K-ac proteins are enriched in metabolic
      processes, essential for its adaptation in its hosts. We also identified in both
      parasites a quite variable N-terminal acetylation sites. Our results suggest that
      protein acetylation is involved in differential regulation of multiple cellular
      processes in Trypanosomes, contributing to our understanding of the essential
      mechanisms for parasite infection and survival.

PMID- 29168383
TI  - Synthesis of the C(1)-C(13) Fragment of Leiodermatolide via Hydrogen-Mediated C-C
      Bond Formation.
AB  - The C(1)-C(13) fragment of the antimitotic marine macrolide leiodermatolide is
      prepared in seven steps via hydrogenative and transfer-hydrogenative reductive C
      C couplings. A hydrogen-mediated reductive coupling of acetylene with a Roche
      type aldehyde is used to construct C(7)-C(13). A 2-propanol-mediated reductive
      coupling of allyl acetate with (E)-2-methylbut-2-enal at a low loading of iridium
      (1 mol %) is used to construct C(1)-C(6), which is converted to an allylsilane
      using Oestereich's copper-catalyzed allylic substitution of Si-Zn reagents. The
      union of the C(1)-C(6) and C(7)-C(13) fragments is achieved via stereoselective
      Sakurai allylation.

PMID- 29168384
TI  - Tracking Silent Hypersensitivity Reactions to Asparaginase during Leukemia
      Therapy Using Single-Chip Indirect Plasmonic and Fluorescence Immunosensing.
AB  - Microbial asparaginase is an essential component of chemotherapy for the
      treatment of childhood acute lymphoblastic leukemia (cALL). Silent
      hypersensitivity reactions to this microbial enzyme need to be monitored
      accurately during treatment to avoid adverse effects of the drug and its silent
      inactivation. Here, we present a dual-response anti-asparaginase sensor that
      combines indirect SPR and fluorescence on a single chip to perform ELISA-type
      immunosensing, and correlate measurements with classical ELISA. Analysis of serum
      samples from children undergoing cALL therapy revealed a clear correlation
      between single-chip indirect SPR/fluorescence immunosensing and ELISA used in
      clinical settings (R2 > 0.9). We also report that the portable SPR/fluorescence
      system had a better sensitivity than classical ELISA to detect antibodies in
      clinical samples with low antigenicity. This work demonstrates the reliability of
      dual sensing for monitoring clinically relevant antibody titers in clinical serum
      samples.

PMID- 29168385
TI  - Luminescence Anisotropy and Thermal Effect of Magnetic and Electric Dipole
      Transitions of Cr3+ Ions in Yb:YAG Transparent Ceramic.
AB  - In this article, we present an in-depth optical study on luminescence spectral
      features and the thermal effect of the magnetic dipole (MD) transitions (e.g.,
      the R lines of 2E -> 4A2) and the associated electric dipole transitions (e.g.,
      phonon-induced sidebands of the R lines) of Cr3+ ions in ytterbium-yttrium
      aluminum garnet polycrystalline transparent ceramic. The doubly split R lines
      predominately due to the doublet splitting of the 2E level of the Cr3+ ion in an
      octahedral crystal field are found to show a very large anisotropy in both
      emission intensity and thermal broadening. The large departure from the intensity
      equality between them could be interpreted in terms of large difference in
      coupling strength with phonons for the doubly split states of the 2E level. For
      the large anisotropy in thermal broadening, very different effective Debye
      temperatures for the two split states may be responsible for it. Besides the 2E
      excited state, the higher excited states, for example, 4T1 and 4T2 of the Cr3+
      ion, also exhibit a very large inequality in coupling strength with phonons at
      room temperature. By examining the Stokes phonon sidebands of the MD R lines at
      low temperatures with the existing ion-phonon coupling theory, we reveal that
      they indeed carry fundamental information of phonons. For example, their broad
      background primarily reflects Debye density of states of acoustic phonons. These
      new results significantly enrich our existing understanding on interesting but
      challenging luminescence mechanisms of ion-phonon coupling systems.

PMID- 29168386
TI  - Carbon Nanotube-Doped Adhesive Films for Detecting Crack Propagation on Bonded
      Joints: A Deeper Understanding of Anomalous Behaviors.
AB  - A novel nanoreinforced adhesive film has been developed to detect adhesive
      deformation and crack propagation along the bonding line by means of the
      electrical response of the material. Adhesive films were doped by spraying an
      aqueous dispersion of carbon nanotubes (CNTs) over the surface. To determine the
      sensitivity of bonded joints, single lap shear (SLS) and mode-I fracture energy
      tests have been carried out while their electrical response has been measured. It
      has been found that CNT-doped adhesive films are able to detect adhesive
      deformation and final failure for SLS specimens and crack initiation and
      propagation along the bonding line for mode-I specimens with a high sensitivity.
      Sudden increases on electrical resistance are correlated to a rapid growing of
      the crack length due to instability on crack propagation in a tick-slip case,
      whereas specimens with a more uniform crack propagation are linked to a steadier
      increase on electrical resistance, and both of them are properly correlated to
      the mechanical response. By analyzing more in detail the electrical response and
      comparing with theoretical approaches, the stick-slip behavior is associated with
      the presence of porosity and lack of adhesives because of possible manufacturing
      issues such as adhesive overflowing. These statements are also validated by
      microstructural analysis. Therefore, the potential and applicability of the
      proposed adhesive films for evaluating the structural integrity has been
      demonstrated.

PMID- 29168387
TI  - Impacts of sodium-glucose co-transporter type 2 inhibitors on central blood
      pressure.
AB  - AIMS: To assess the effects of sodium-glucose co-transporter type 2 inhibitors on
      central blood pressure, an important determinant of cardiovascular events.
      METHODS: Canagliflozin, Empagliflozin or Luseogliflozin was given for 102 type 2
      diabetic patients with hypertension and nephropathy. Central blood pressure was
      evaluated by radial tonometry. Clinical parameters were followed for 6 months.
      RESULTS: Three differing sodium-glucose co-transporter type 2 inhibitors
      similarly reduced brachial and central blood pressures, casual blood sugar,
      haemoglobin A1c, estimated glomerular filtration rate and albuminuria without
      significant changes in pulse rate and lipid profiles. Central systolic blood
      pressure was associated with the decreases in albuminuria by sodium-glucose co
      transporter type 2 inhibitors. CONCLUSION: Comparable influences of various
      sodium-glucose co-transporter type 2 inhibitors on central blood pressure suggest
      class effects.

PMID- 29168388
TI  - Primer in Genetics and Genomics, Article 6: Basics of Epigenetic Control.
AB  - The epigenome is a collection of chemical compounds that attach to and overlay
      the DNA sequence to direct gene expression. Epigenetic marks do not alter DNA
      sequence but instead allow or silence gene activity and the subsequent production
      of proteins that guide the growth and development of an organism, direct and
      maintain cell identity, and allow for the production of primordial germ cells
      (PGCs; ova and spermatozoa). The three main epigenetic marks are (1) histone
      modification, (2) DNA methylation, and (3) noncoding RNA, and each works in a
      different way to regulate gene expression. This article reviews these concepts
      and discusses their role in normal functions such as X-chromosome inactivation,
      epigenetic reprogramming during embryonic development and PGC production, and the
      clinical example of the imprinting disorders Angelman and Prader-Willi syndromes.

PMID- 29168389
TI  - A new steroidal saponin from Polygonatum sibiricum.
AB  - A new furostan type steroidal saponin, kingianoside Z (1), along with four known
      compounds (2-5), was isolated from the ethanolic extract of Polygonatum sibiricum
      Delar. ex Redoute. Their structures were determined by spectroscopical method and
      by comparison with previously reported spectroscopic data. Compounds 3-5 showed
      significant cytotoxicity against HepG2 cell lines with IC50 values of 14.2, 12.1
      and 8.5 MUM, respectively.

PMID- 29168390
TI  - The adaptation of everyday practices in the adoption of chronic illness.
AB  - This article uses social practice theory to examine the role of information
      seeking in the maintenance of existing lifestyle and illness-related adjustments
      in the context of chronic illnesses. The research findings are derived from a
      thematic analysis of 16 semi-structured in-depth interviews with Estonian
      Parkinson's disease patients. The coding scheme bases on the four practice
      elements outlined by Schatzki (practical understandings, rules, teleological
      structures and general understandings) and other categories related to chronic
      illness self-management skills, bodily movements, daily routines and information
      seeking practices. The findings reveal that people with chronic illness value
      maintaining their existing lifestyles as long as possible and the willingness to
      seek out illness-related information is related to the severity and duration of
      the disease. These findings suggest that effective illness-related communication
      that supports self-management should provide patients with possibilities to
      adjust and switch between practices in a time and a pace that is natural and
      acceptable to them.

PMID- 29168391
TI  - Building creative communities of care: Arts, dementia, and hope in the United
      States.
AB  - This essay explores the history of the cultural community development model in
      the United States and its potential benefits for transforming the lived
      experience of dementia. Using her work with the 2011 Penelope Project as a case
      study, the author identifies core elements of a "Creative Community of Care:"
      open systems; all activities are accessible; the arts are immersed into the
      environment of care; projects build on existing assets and rituals; projects
      evolve over long periods of time; and projects have high cultural value/capital.

PMID- 29168392
TI  - The Role of Caregivers in Physical Activity for Older Adults With Alzheimer's
      Disease.
AB  - This study examined the determinants of physical activity (PA) for older adults
      with Alzheimer's disease (AD) to learn more about how to promote PA in this
      population. Caregivers of older adults with AD (N = 99) provided information
      related to care recipient's PA, as well as addressed sociodemographics and
      perceptions about their care recipient's PA. Gender of care recipient was a
      significant predictor of PA (beta = .80, P < .05); men with AD participated in
      more PA than women with AD. Also, caregiver's outcome expectation for care
      recipient's PA also predicted more PA (beta = .82, P < .05). Caregiver's
      perceived benefits of PA (outcome expectation) for their care recipient partially
      mediated the relationship between self-efficacy for care recipient's PA and the
      reported levels of PA for the care recipient. This study demonstrated the
      importance of caregiver perceptions about care recipient's PA.

PMID- 29168393
TI  - Serum sclerostin in vascular calcification and clinical outcome in chronic kidney
      disease.
AB  - Sclerostin, a potent soluble inhibitor of the Wnt signalling pathway, is known to
      inhibit bone formation by suppressing osteocytes differentiation and function.
      Patients with chronic kidney disease have high levels of serum sclerostin.
      Sclerostin has been implicated in the pathogenesis of vascular calcification,
      which may promote the cardiovascular events of morbidity and mortality in chronic
      kidney disease patients. However, the role of sclerostin in vascular
      calcification and clinical prognosis in chronic kidney disease remains elusive.
      While some studies suggested a positive correlation between serum sclerostin and
      vascular calcification or clinical outcome, other studies showed no or even
      negative correlation between them. Small sample size, heterogeneity in enrolled
      patients, discrepancy in anatomical structure examined and differences in the
      applied assays may be responsible for the discrepant results. Nonetheless, anti
      sclerostin antibodies may be a new therapeutic approach to increase bone mass and
      strength in chronic kidney disease. This review aims to have a better
      understanding of the relationship of serum sclerostin with vascular calcification
      and clinical outcome in chronic kidney disease patients, and propose the
      application of anti-sclerostin therapy in chronic kidney disease.

PMID- 29168394
TI  - Documentation of Child Maltreatment in Electronic Health Records.
AB  - International Classification of Diseases codes for child maltreatment can aid
      surveillance and research, but the extent to which they are used is not well
      established. We documented prevalence of the use of maltreatment-related codes,
      examined demographic characteristics of youth assigned these codes, and compared
      results with previous studies. Data were extracted from electronic health records
      of 0- to 21-year-olds assigned 1 of 15 maltreatment-related International
      Classification of Diseases, Ninth Revision, codes who had encounters in a large
      medical system over a 4-year period. Only 0.02% of approximately 2.5 million
      youth had a maltreatment-related code, replicating other studies. Results provide
      a dramatic contrast to much higher rates based on self-report or informant-report
      and referrals to Child Protective Services. Lack of documentation of maltreatment
      in electronic health records can lead to missed chances at early intervention,
      inadequate coordination of health care, insufficient allocation of resources to
      addressing problems related to maltreatment, and flawed public health data.

PMID- 29168395
TI  - Polyketides from Pestalotiopsis zonata and structure revision of pestalrones A
      and B.
AB  - The structures of pestalrones A-B were revised via reinterpretation of the NMR
      data and a brief chemical transformation from the co-occurring polyketides, in
      our investigation on the secondary metabolites of Pestalotiopsis zonata, which
      also afforded a new alpha-pyrone derivative, pestazonatic acid, and four known
      analogs.

PMID- 29168396
TI  - Intra-rater repeatability of gait parameters in healthy adults during self-paced
      treadmill-based virtual reality walking.
AB  - Self-paced treadmill walking is becoming increasingly popular for the gait
      assessment and re-education, in both research and clinical settings. Its day-to
      day repeatability is yet to be established. This study scrutinised the test
      retest repeatability of key gait parameters, obtained from the Gait Real-time
      Analysis Interactive Lab (GRAIL) system. Twenty-three male able-bodied adults
      (age: 34.56 +/- 5.12 years) completed two separate gait assessments on the GRAIL
      system, separated by 5 +/- 3 days. Key gait kinematic, kinetic, and spatial
      temporal parameters were analysed. The Intraclass-Correlation Coefficients (ICC),
      Standard Error Measurement (SEM), Minimum Detectable Change (MDC), and the 95%
      limits of agreements were calculated to evaluate the repeatability of these gait
      parameters. Day-to-day agreements were excellent (ICCs > 0.87) for spatial
      temporal parameters with low MDC and SEM values, <0.153 and <0.055, respectively.
      The repeatability was higher for joint kinetic than kinematic parameters, as
      reflected in small values of SEM (<0.13 Nm/kg and <3.4 degrees ) and MDC (<0.335
      Nm/kg and <9.44 degrees ). The obtained values of all parameters fell within the
      95% limits of agreement. Our findings demonstrate the repeatability of the GRAIL
      system available in our laboratory. The SEM and MDC values can be used to assist
      researchers and clinicians to distinguish 'real' changes in gait performance over
      time.

PMID- 29168399
TI  - Vacuolar ATPase as a possible therapeutic target in human acute myeloid leukemia.
AB  - INTRODUCTION: V-ATPase is a proton pump expressed both in the membrane of
      intracellular organelles (e.g. endosomes, lysosomes, Golgi structures) and the
      plasma membrane. It is an important regulator of organellar functions,
      intracellular molecular trafficking, intercellular communication and
      intracellular signaling. It is therefore considered as a possible therapeutic
      target in the treatment of human malignancies. Areas covered: Relevant
      publications were identified through literature searches in the PubMed database.
      We searched for original articles and reviews describing the possible importance
      of V-ATPase for leukemogenesis and chemosensitivity in human myeloid cells,
      especially acute myeloid leukemia (AML) cells. Expert commentary: The expression
      of V-ATPase in the primary human AML cells varies between patients, and high
      levels are associated with high constitutive release of a wide range of soluble
      mediators. Several of the molecules included in the V-ATPase interactome may also
      be important in leukemogenesis and/or development of chemoresistance in human
      AML. Therapeutic targeting of V-ATPase should therefore be regarded as a possible
      therapeutic strategy in human AML, but the efficiency of such targeting will
      probably differ between patients. The possibility of toxicity, especially
      hematological toxicity and immunosuppression, also has to be clarified.

PMID- 29168398
TI  - Paraoxonase, arylesterase and lactonase activities of paraoxonase-1 (PON1) in
      obese and severely obese women.
AB  - Obesity is independently associated with disturbances in lipid and lipoprotein
      metabolism, oxidative stress, and is a well-established independent risk factor
      for cardiovascular diseases (CVD). Human paraoxonase 1 (PON1) is a pleotropic
      high-density lipoprotein (HDL)-associated enzyme with antioxidant and anti
      inflammatory proprieties that have been suggested to contribute to the athero
      protective function of the lipoprotein. The aim of this study was to investigate
      whether obesity is associated with PON1 activity and whether this association is
      influenced by oxidative stress, inflammation and HDL cholesterol (HDL-C)
      concentration. The promiscuous activities, arylesterase and paraoxonase, and the
      putative physiological activity, lactonase, of PON1 were assessed in the serum of
      214 obese and severely obese, 101 overweight and 129 normal-weight women. Levels
      of high-sensitivity C-reactive protein (hs-CRP), hydroperoxides (by-products of
      lipid oxidative damage) and lipid profiles were also evaluated. Arylesterase
      activity was the only activity that significantly differed across the groups
      (ANOVA, p < .01), with the greatest decrease observed in individuals with body
      mass index (BMI) > 40 kg/m2 compared to controls (p < .001). This activity was
      also inversely, although weakly (r = -0.160, p < .001) correlated with the BMI,
      and the association was independent of age and levels of oxidative stress and
      inflammation, but not of HDL-C concentration. In conclusion, our results suggest
      that the apparent obesity-associated decrement of PON1 activity might simply
      reflect the decrease in concentration of its plasmatic carrier.

PMID- 29168400
TI  - Cardiovascular disease patients have increased risk for comorbidity: A cross
      sectional study in the Netherlands.
AB  - BACKGROUND: Comorbidity is a cause of increased mortality, decreased quality of
      life and increased use of healthcare services. It is important particularly for
      physicians and other healthcare providers in primary care settings to evaluate
      these patients properly. Cardiovascular diseases (CVD) are the most common cause
      of death from non-communicable diseases worldwide and are characterized by a high
      level of comorbidities. OBJECTIVES: To address the distribution of CVDs and
      comorbidities across sociodemographic groups and associations between CVDs and
      comorbidities. METHODS: A cross-sectional study was conducted using data of 67
      786 patients. Data were collected by the Registration Network Family Practices
      (RegistratieNet Huisartspraktijken, RNH). Comorbidities were analysed using chi
      square and logistic regression analyses. RESULTS: At the time of study, 26.5% of
      the patients had at least one CVD and 10.5% of patients had two or more CVD
      diagnoses. The strongest association within cardiovascular diseases were between
      health failure and arrhythmias (OR: 9.20; 95%CI: 7.78-10.89). Coronary artery
      disease and hypertension had strong relationship with diabetes (OR: 2.22; 95%CI:
      2.02-2.45, OR: 2.22; 95%CI: 2.02-2.45 respectively) and lipid metabolism
      disorders (OR: 2.04; 95%CI: 1.87-2.23, OR: 2.04; 95%CI: 1.87-2.23, respectively).
      The strongest associations for cerebrovascular diseases were with epilepsy (OR:
      4.09; 95%CI: 3.29-5.10) and arrhythmias (OR: 2.23; 95%CI: 1.99-2.50). CONCLUSION:
      One out of every four patients suffered from at least one CVD. Having one CVD
      increased the risk of another, co-occurring CVD and a higher number of other
      chronic diseases.

PMID- 29168401
TI  - The clinical benefit of hyperthermia in pancreatic cancer: a systematic review.
AB  - OBJECTIVE: In pancreatic cancer, which is therapy resistant due to its hypoxic
      microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The
      aim of this systematic review is to investigate the validity of the hypothesis
      that hyperthermia added to radiotherapy and/or chemotherapy improves treatment
      outcome for pancreatic cancer patients. METHODS AND MATERIALS: We searched
      MEDLINE and Embase, supplemented by handsearching, for clinical studies involving
      hyperthermia in pancreatic cancer patients. The quality of studies was evaluated
      using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary
      outcome was treatment efficacy; we calculated overall response rate and the
      weighted estimate of the population median overall survival (mp) and compared
      these between hyperthermia and control cohorts. RESULTS: Overall, 14 studies were
      included, with 395 patients with locally advanced and/or metastatic pancreatic
      cancer of whom 248 received hyperthermia. Patients were treated with regional (n
      = 189), intraoperative (n = 39) or whole-body hyperthermia (n = 20), combined
      with chemotherapy, radiotherapy or both. Quality of the studies was low, with
      level of evidence 3 (five studies) and 4. The six studies including a control
      group showed a longer mp in the hyperthermia groups than in the control groups
      (11.7 vs. 5.6 months). Overall response rate, reported in three studies with a
      control group, was also better for the hyperthermia groups (43.9% vs. 35.3%).
      CONCLUSIONS: Hyperthermia, when added to chemotherapy and/or radiotherapy, may
      positively affect treatment outcome for patients with pancreatic cancer. However,
      the quality of the reviewed studies was limited and future randomised controlled
      trials are needed to establish efficacy.

PMID- 29168402
TI  - Liquid metal bath as conformable soft electrodes for target tissue ablation in
      radio-frequency ablation therapy.
AB  - BACKGROUND: Radio-frequency ablation has been an important physical method for
      tumor hyperthermia therapy. The conventional rigid electrode boards are often
      uncomfortable and inconvenient for performing surgery on irregular tumors,
      especially for those tumors near the joints, such as ankles, knee-joints or other
      facets like finger joints. MATERIAL AND METHODS: We proposed and demonstrated a
      highly conformable tumor ablation strategy through introducing liquid metal bath
      as conformable soft electrodes. Different heights of liquid metal bath electrodes
      were adopted to perform radio-frequency ablation on targeted tissues. Temperature
      and ablation area were measured to compare the ablation effect with plate metal
      electrodes. RESULTS: The recorded temperature around the ablation electrode was
      almost twice as high as that with the plate electrode and the effective ablated
      area was 2-3 fold larger in all the mimicking situations of bone tumors, span
      shaped or round-shaped tumors. Another unique feature of the liquid metal
      electrode therapy is that the incidence of heat injury was reduced, which is a
      severe accident that can occur during the treatment of irregular tumors with
      plate metal boards. CONCLUSIONS: The present method suggests a new way of using
      soft liquid metal bath electrodes for targeted minimally invasive tumor ablation
      in future clinical practice.

PMID- 29168403
TI  - Inclusionary othering: A key threshold concept for healthcare education.

PMID- 29168404
TI  - Impact of a chronic pain management pathway on opioid administration and
      prescribing in an Emergency Department.
AB  - CONTEXT: Prescription opioid abuse and misuse is a significant public health
      crisis. In 2012, an opioid prescribing pathway for patients with chronic pain
      presenting to the Emergency Department (ED) was implemented. The objective of
      this study is to determine the impact of the pathway for administration of
      opioids in the ED as well as the prescribing of opioids for home use after
      discharge. METHODS: Retrospective pre- and post-intervention time series study of
      consecutive patients presenting to the ED with acute and chronic pain complaints
      before and after implementation of the pathway. For the purposes of this study,
      we included patients with chronic abdominal or back pain - defined as pain
      present for greater than three months - and acute pain as acute long bone
      fracture. RESULTS: Before pathway implementation, there was no statistically
      significant difference in the mean morphine equivalent (MEQ) dose administered
      for chronic or acute pain patients. After pathway implementation, there was a
      decrease in IV/IM morphine administered to patients with chronic pain (p = .0200)
      but not to patients with acute pain (p = .0820). Overall, MEQs administered did
      not change in either group. In the acute pain group, no significant differences
      were found in the number of patients who received opioid prescriptions upon
      discharge (p = .7749). However, in the chronic pain group, the number of patients
      who received opioid prescriptions upon discharge decreased with statistical
      significance (p = .0017). CONCLUSIONS: After the implementation of a chronic pain
      management pathway in an ED, there is a decrease noted in opioids administered to
      patients with chronic pain both in the ED and prescriptions on discharge. In
      patients presenting with acute pain, there was no change in administration or
      prescription of opioids.

PMID- 29168405
TI  - Acrylamide attenuated immune tissues' function via induction of apoptosis and
      oxidative stress: Protection by l-carnitine.
AB  - Acrylamide (ACR), with high prevalence in starchy food, has been associated with
      the development of several organ toxicities such as immunotoxicity. This study
      aimed to demonstrate the role of oxidative stress and apoptosis as the mechanisms
      involved in ACR-induced immunotoxicity in mice. Mice were randomly assigned to
      six groups and treated as follows: control (normal saline), cyclophosphamide (200
      mg kg-1), ACR groups (12.5, 25 and 50mg kg-1, orally), and l-carnitine (l-CAR;
      100 mg kg-1) + ACR (50 mg kg-1). After 30 days of exposure, mice were killed and
      immunotoxic response was evaluated via immune blood cells count and body/organ
      weights. Oxidative stress parameters and pathological examination were done in
      thymus and spleen. Also, the apoptosis was evaluated via flow cytometric by
      annexin V/FITC kit in the splenocytes. Our results indicated that ACR could
      induce immunotoxicity characterized by reduction in immune blood cells,
      body/organ weights, and pathological changes in spleen. The assessment of
      oxidative stress markers revealed increase in lipid peroxidation, protein
      carbonyl content, and depletion of glutathione level. Also, increased apoptosis
      was observed in splenocytes after ACR administration compared to the control
      group. These alterations were markedly normalized by coadministration of l-CAR
      (as a potent antioxidant). Taken together, the results of this study showed the
      potential of ACR to induce immunotoxicity through provoking oxidative stress and
      inducing apoptosis and the protective effect of l-CAR to attenuate this toxicity.
      These findings will help in elucidating the toxicity mechanism induced by ACR.

PMID- 29168407
TI  - Mortality and recurrence rates among systemically untreated high risk breast
      cancer patients included in the DBCG 77 trials.
AB  - BACKGROUND: Following loco-regional treatment for early breast cancer accurate
      prognostication is essential for communicating benefits of systemic treatment.
      The aim of this study was to determine time to recurrence and long-term mortality
      rates in high risk patients according to patient characteristics and subtypes as
      assigned by immunohistochemistry panels. PATIENTS AND METHODS: In November 1977
      through January 1983, 2862 patients with tumors larger than 5 cm or positive
      axillary nodes were included in the DBCG 77 trials. Archival tumor tissue from
      patients randomly assigned to no systemic treatment was analyzed for ER, PR,
      Ki67, EGFR and HER2. Intrinsic subtypes were defined as follows: Luminal A, ER or
      PR >0%, HER2-negative, PR >10% and Ki67 < 14%; Luminal B, ER or PR >0%, (PR <=10%
      or HER2-positive or Ki67 >= 14%); HER2E, ER 0%, PR 0%, HER2 positive; Core basal,
      ER 0%, PR 0%, HER2 negative and EGFR positive. Multivariate categorical and
      fractional polynomials (MFP) models were used to construct prognostic subsets by
      clinicopathologic characteristics. RESULTS: In a multivariate model, mortality
      rate was significantly associated with age, tumor size, nodal status, invasion,
      histological type and grade, as well as subtype classification. CONCLUSIONS: With
      35 years of follow-up, in this population of high-risk patients with no systemic
      therapy, no subgroup based on a composite prognostic score and/or molecular
      subtypes could be identified without excess mortality as compared to the
      background population.

PMID- 29168408
TI  - Main messages for primary care from the 2016 European Guidelines on
      cardiovascular disease prevention in clinical practice.
AB  - In 2016, a new version of the European Guidelines on Cardiovascular Prevention
      was released, representing a partnership between the European Association for
      Cardiovascular Prevention and Rehabilitation of the European Society of
      Cardiology (ESC) and nine European societies, including Wonca-Europe. The ESC
      guidelines underscore the importance of a lifetime approach to cardiovascular
      (CV) risk since both CV risk and prevention are dynamic and continuous as
      patients' age and/or accumulate co-morbidities. Healthy people of all ages should
      be encouraged to adopt a healthy lifestyle, as well as improved lifestyle and
      reduced risk factor levels are paramount in patients at increased risk of
      developing cardiovascular disease (CVD) and in those with established CVD.
      Healthcare professionals, and especially general practitioners, play an important
      role in helping patients achieve this and should set a personal example of
      healthy lifestyle behaviour. The ESC guidelines are based on 'to do' and 'not to
      do' messages. Of note, what remains uncertain is stated at the end of each
      dedicated chapter, confirming that guidelines are not absolute rules, and should
      be interpreted in the light of the healthcare worker's knowledge and experience,
      patient preferences and the local social, cultural and economic situation.

PMID- 29168409
TI  - How do Swiss general practitioners agree with and report adhering to a top-five
      list of unnecessary tests and treatments? Results of a cross-sectional survey.
AB  - BACKGROUND: In 2014, the 'Smarter Medicine' campaign released a top five list of
      unnecessary tests and treatments in Swiss primary care, such as imaging for acute
      low-back pain and long-term prescribing of proton pump inhibitors. OBJECTIVES:
      Measure general practitioners' (GPs) agreement with the recommendations and self
      reported adherence. METHODS: Cross-sectional, online survey of GPs in the 'Swiss
      primary care active monitoring' (SPAM) network, which assessed awareness of
      'Smarter Medicine' and views on each recommendation. Questions included whether
      the clinical situation is common, whether the recommendation is followed, whether
      GPs agree with the recommendation and reasons why the recommendation would not be
      followed. RESULTS: One-hundred-and-sixty-seven of 277 GPs from the SPAM network
      participated (60%), of which 104 (62%) knew of 'Smarter Medicine', including 79%
      in German areas, 49% in French areas and 38% in Italian areas (P < 0.001).
      Agreement with the five recommendations was high, with scores around nine out of
      10. The proportion saying they typically follow each recommendation was 68 to
      74%, except not continuing long-term PPI prescriptions without attempting dose
      reduction, with only 34%. Common reasons for not following the recommendations
      were patient or other provider requests and situations that might suggest the
      need for more aggressive care. CONCLUSION: Two years after the launch of the
      campaign, awareness and acceptance of 'Smarter Medicine' appear to be high among
      Swiss GPs. By self-report, the recommendations are adhered to by most of the
      respondents but there may be room for improvement, especially for long-term PPI
      prescriptions.

PMID- 29168410
TI  - Response to the letter to the editor 'reliability of rapid urease test for
      screening gastric cancer in high-risk populations'.

PMID- 29168406
TI  - TGFbeta as a therapeutic target in cystic fibrosis.
AB  - INTRODUCTION: Cystic fibrosis (CF) is a genetic disease characterized by
      progressive lung disease. Most CF therapies focus on treating secondary pulmonary
      complications rather than addressing the underlying processes inducing airway
      remodeling and ineffective response to infection. Transforming growth factor beta
      (TGFbeta) is a cytokine involved in fibrosis, inflammation, and injury response
      as well as a genetic modifier and biomarker of CF lung disease. Targeting the
      TGFbeta pathway has been pursued in other diseases, but the mechanism of TGFbeta
      effects in CF is less well understood. Areas covered: In this review, we discuss
      CF lung disease pathogenesis with a focus on potential links to TGFbeta. TGFbeta
      signaling in lung health and disease is reviewed. Recent studies investigating
      TGFbeta's impact in CF airway epithelial cells are highlighted. Finally, an
      overview of potential therapies to target TGFbeta signaling relevant to CF are
      addressed. Expert opinion: The broad impact of TGFbeta signaling on numerous
      cellular processes in homeostasis and disease is both a strength and a challenge
      to developing TGFbeta dependent therapeutics in CF. We discuss the challenges
      inherent in developing TGFbeta-targeted therapy, identifying appropriate patient
      populations, and questions regarding the timing of treatment. Future directions
      for research into TGFbeta focused therapeutics are discussed.

PMID- 29168411
TI  - Primary healthcare policy implementation in the Eastern Mediterranean region:
      Experiences of six countries.
AB  - BACKGROUND: Primary healthcare (PHC) is essential for equitable access and cost
      effective healthcare. This makes PHC a key factor in the global strategy for
      universal health coverage (UHC). Implementing PHC requires an understanding of
      the health system under prevailing circumstances, but for most countries, no data
      are available. OBJECTIVES: This paper describes and analyses the health systems
      of Bahrain, Egypt, Lebanon, Qatar, Sudan and the United Arab Emirates, in
      relation to PHC. METHODS: Data were collected during a workshop at the WONCA East
      Mediterranean Regional Conference in 2017. Academic family physicians (FP)
      presented their country, using the WONCA framework of 11 PowerPoint slides with
      queries of the country demographics, main health challenges, and the position of
      PHC in the health system. RESULTS: All six countries have improved the health of
      their populations, but currently face challenges of non-communicable diseases,
      aging populations and increasing costs. Main concerns were a lack of trained FPs
      in community settings, underuse of prevention and of equitable access to care.
      Countries differed in the extent to which this had resulted in coherent policy.
      CONCLUSION: Priorities were (i) advocacy for community-based PHC to policymakers,
      including the importance of coordination of healthcare at the community level,
      and UHC to respond to the needs of populations; (ii) collaboration with
      universities to include PHC as a core component of every medical curriculum;
      (iii) collaboration with communities to improve public understanding of PHC; (iv)
      engagement with the private sector to focus on PHC and UHC.

PMID- 29168412
TI  - Persistent symptoms in patients with Crohn's disease in remission: An exploratory
      study on the role of diet.
AB  - OBJECTIVES: Patients with Crohn's disease (CD) often report food
      hypersensitivities with gastrointestinal (GI) symptoms despite being in clinical
      remission. We aimed to identify the most frequent symptoms and dietary triggers
      in such patients, and also explored whether a strict elimination diet may reduce
      their GI symptoms. METHODS: We assessed GI symptoms and dietary triggers in 16
      patients with CD in clinical remission. Of these, 12 patients subsequently
      participated in a dietary intervention trial: two weeks on a habitual diet
      including wheat and dairy products followed by two weeks of a strict elimination
      diet. The severity of seven symptoms (overall symptoms, abdominal pain, bloating,
      abnormal feces, wind, fatigue, and musculoskeletal pain) was measured by using
      visual analog scales throughout the four weeks intervention period. MAIN RESULTS:
      The most common symptoms were abdominal pain, wind, bloating, odorous wind/feces,
      and diarrhea. Dairy and wheat products were reported as the most frequent dietary
      symptom triggers. All symptoms improved (p < .05) during the elimination diet
      period, especially in patients with small intestinal affection. CONCLUSION: Our
      exploratory study suggests that dietary interventions such as an elimination diet
      may reduce GI symptoms in patients with CD in remission.

PMID- 29168413
TI  - Computational prediction of the phenotypic effects of genetic variants: basic
      concepts and some application examples in Drosophila nervous system genes.
AB  - Predicting the phenotypic impact of mutations is a central challenge in
      population and functional genetics. The analysis of DNA and amino acid sequence
      variation in an evolutionary context is a robust approach to infer the fitness
      effects of genetic variants. In this review, we discuss the most popular methods
      based on this approach, covering both theoretical and practical aspects, and
      introduce compelling software for predicting the functional effects of mutations,
      and to highlight functionally relevant nucleotide or amino acid candidate
      positions. Furthermore, we provide some examples of their application to
      Drosophila genes affecting significant aspects of the development, physiology and
      function of the nervous system.

PMID- 29168414
TI  - Knowledge, competencies and attitudes regarding external post-mortem physical
      examination: A survey among German post-graduate trainees in general practice.
AB  - BACKGROUND: The external post-mortem examination (EPME) is an important medical,
      legal and socio-economic task with far-reaching relevance; however, due to
      discrepancies between findings from EPMEs and actual cause of death, improvements
      in accuracy and quality are needed. OBJECTIVES: To investigate knowledge,
      competencies and attitudes regarding EPME in general practitioner (GP) post
      graduate trainees. METHODS: Before four post-graduate training courses on the
      EPME for general practitioner trainees, organized in 2014 in the German federal
      state of Baden-Wuerttemberg, a questionnaire on the EPME was distributed by the
      lecturer, completed by the GP post-graduate trainees and returned to the
      lecturer. The questionnaire consisted of 19 items related to three main
      categories: knowledge, competencies and attitudes. RESULTS: Out of 380 GP post
      graduate trainees, 128 completed and returned the questionnaire (response rate
      33.7%). Less than 18% felt adequately confident in identifying a natural cause of
      death and less than 5% felt adequately confident in identifying an unnatural
      cause of death. Only 33% consistently fully uncover the corpse for the EPME.
      CONCLUSION: We found an important uncertainty in GP post-graduate trainees
      regarding their EPME knowledge and competencies.

PMID- 29168415
TI  - Clinically intractable chronic unilateral hematuria: Successful treatment with
      renal segmental artery embolization.
AB  - Chronic unilateral hematuria (CUH) is characterized by intermittent or continuous
      gross hematuria that cannot be diagnosed using standard radiology and hematology.
      The authors report a case of CUH with no discrete lesion at ureteroscopy,
      successfully treated by selective renal artery embolization. Renal artery
      embolization could be a treatment option for selected patients with clinically
      intractable CUH.

PMID- 29168416
TI  - A Danish national effort of BRCA1/2 variant classification.

PMID- 29168418
TI  - Telemedicine in Diabetic Foot Care: A Systematic Literature Review of
      Interventions and Meta-analysis of Controlled Trials.
AB  - The care of individuals with diabetic foot ulcers is costly and requires multiple
      hospital visits. Inadequate care leads to serious complications and a high risk
      of lower extremity amputation. In this review, we aimed at evaluating whether
      telemedicine can be effective in diabetic foot patient care. We searched Medline
      through Embase and PubMed and Cochrane Central Register of Controlled Trials
      (CENTRAL) for relevant studies, published up to April 2017. The studies were
      summarized and discussed in a narrative method and a meta-analysis of 2
      controlled trials was conducted using the fixed-effects model. The main outcomes,
      assessed in the retrieved studies were the healing rate and satisfaction of
      patients and health care personnel. Most of the studies showed that implementing
      telemonitoring programs increased the rate of complete ulcer healing, while the
      patients were highly satisfied. Two trials providing data on 213 patients on
      telemedicine and 301 patients on usual care were included for meta-analysis.
      Subjects in telemedicine, as well as control groups had statistically similar
      healing time (43 vs 45 days; P = .83), healing time ratio adjusted for age (1 vs
      1.4; P = .1), unhealed ulcers or loss to follow-up (3 of 20 vs 7 of 120; P =
      .13), and amputations (12 of 193 vs 14 of 182; P = .59). Subjects in the
      telemedicine group experienced a significantly higher mortality rate (8 of 193 vs
      1 of 181; P = .0001) due to unexplained factors. No adverse events were
      attributed to using the telemedicine technology. The odds of complete ulcer
      healing were statistically similar between the telemedicine group and controls
      (odds ratio = 0.86; 95% CI = 0.57-1.33; P = .53). Telemedicine care is promising
      for the management of diabetic foot patients as the results were comparable with
      usual care. However, further large-scale studies need to be undertaken before it
      can be implemented widely.

PMID- 29168417
TI  - A DNA segment encoding the anticodon stem/loop of tRNA determines the specific
      recombination of integrative-conjugative elements in Acidithiobacillus species.
AB  - Horizontal gene transfer is crucial for the adaptation of microorganisms to
      environmental cues. The acidophilic, bioleaching bacterium Acidithiobacillus
      ferrooxidans encodes an integrative-conjugative genetic element (ICEAfe1)
      inserted in the gene encoding a tRNAAla. This genetic element is actively excised
      from the chromosome upon induction of DNA damage. A similar genetic element
      (ICEAcaTY.2) is also found in an equivalent position in the genome of
      Acidithiobacillus caldus. The local genomic context of both mobile genetic
      elements is highly syntenous and the cognate integrases are well conserved. By
      means of site directed mutagenesis, target site deletions and in vivo
      integrations assays in the heterologous model Escherichia coli, we assessed the
      target sequence requirements for site-specific recombination to be catalyzed by
      these integrases. We determined that each enzyme recognizes a specific small DNA
      segment encoding the anticodon stem/loop of the tRNA as target site and that
      specific positions in these regions are well conserved in the target attB sites
      of orthologous integrases. Also, we demonstrate that the local genetic context of
      the target sequence is not relevant for the integration to take place. These
      findings shed new light on the mechanism of site-specific integration of
      integrative-conjugative elements in members of Acidithiobacillus genus.

PMID- 29168419
TI  - Truncated forms of U2 snRNA (U2-tfs) are shunted toward a novel uridylylation
      pathway that differs from the degradation pathway for U1-tfs.
AB  - During the biogenesis of U1 small nuclear ribonucleoprotein, a small population
      of U1 snRNA molecules acquires an extra methylation at the first transcribed
      nucleotide and a nucleolytic cleavage to remove the 3' structured region
      including the Sm protein-binding site and stem-loop 4. These modifications occur
      before hypermethylation of the monomethylated 5' cap, whereby producing truncated
      forms of U1 snRNA (U1-tfs) that are diverted from the normal pathway to a
      processing body-associated degradation pathway. Here, we demonstrate that a small
      population of U2 snRNA molecules receives post-transcriptional modifications
      similar to those of U1 to yield U2-tfs. Like U1-tfs, U2-tfs molecules were
      produced from transcripts of the U2 snRNA gene having all cis-elements or lacking
      the 3' box. Unlike U1-tfs, however, a portion of U2-tfs received additional
      uridylylation of up to 5 nucleotides in length at position 87 (designated as U2
      tfs-polyU) and formed an Sm protein-binding site-like structure that was
      stabilized by the small nuclear ribonucleoprotein SmB/B' probably as a part of
      heptameric Sm core complex that associates to the RNA. Both U2-tfs and U2-tfs
      polyU were degraded by a nuclease distinct from the canonical Dis3L2 by a process
      catalyzed by terminal uridylyltransferase 7. Collectively, our data suggest that
      U2 snRNA biogenesis is regulated, at least in part, by a novel degradation
      pathway to ensure that defective U2 molecules are not incorporated into the
      spliceosome.

PMID- 29168421
TI  - PET/CT-guided interventions: Indications, advantages, disadvantages and the state
      of the art.
AB  - Positron emission tomography/computed tomography (PET/CT) represents an emerging
      imaging guidance modality that has been applied to successfully guide
      percutaneous procedures such as biopsies and tumour ablations. The aim of the
      present narrative review is to report the indications, advantages and
      disadvantages of PET/CT-guided procedures in the field of interventional oncology
      and to briefly describe the experience gained with this new emerging technique
      while performing biopsies and tumor ablations.

PMID- 29168420
TI  - Vulnerabilities in sequencing and task switching in healthy youth offspring of
      parents with mood disorders.
AB  - INTRODUCTION: Visuospatial processing and task switching are impaired in
      individuals with mood disorders. It is unknown whether early deficits are present
      before mood symptom on set or are related to risk for a specific type of mood
      disorder. To investigate, we compared visual attention and task switching during
      sequencing among never-disordered youth with parental family histories of bipolar
      (BD) and major depressive disorders (MDD) and healthy controls (HC) with no
      personal or family history of psychopathology. METHOD: 8-17-year-old youth of
      parents with BD (n = 31, "BD-risk"), youth of parents with MDD (n = 49, "MDD
      risk"), and demographically similar HC (n = 31, "HC") were examined using the
      Delis-Kaplan Executive Functioning System Trail Making Test. Seed-based resting
      state functional connectivity (RSFC) was collected from a subset of 88
      participants (25 BD-risk, 37 MDD-risk, 26 HC) to investigate group differences in
      RSFC related to visuospatial processing. RESULTS: BD-risk and MDD-risk offspring
      had impaired sequencing and task switching, demonstrated by reduced scores on
      visual scanning, F(2, 108) = 4.12, p = .02, number sequencing, F(2, 88) = 4.75, p
      = .01, letter sequencing, F(2, 108) = 4.24, p = .02, and number-letter
      sequencing, F(2, 108) = 4.66, p = .01, compared to scores in HC. RSFC between the
      posterior cingulate (PCC) and clusters in the subcallosal cortex, amygdala, and
      hippocampus significantly differed among HC, BD-risk, and MDD-risk groups. PCC
      subcallosal/limbic RSFC was positively coupled in the MDD-risk and BD-risk groups
      and negatively coupled in HCs. CONCLUSIONS: Youth at familial risk for mood
      disorders demonstrate visuospatial deficits early in the processing stream.
      Improved methods for identifying at-risk children with the earliest possible
      neurocognitive impairments may inform remediation strategies that could prevent
      mood disorders.

PMID- 29168422
TI  - Evaluation of Youth Enjoyment Toward Physical Activity and Sedentary Behavior.
AB  - PURPOSE: The consensus is that physical activity (PA) and sedentary behavior (SB)
      are independent behaviors, but past findings suggest that they may be influenced
      by common underlying factors. To clarify this issue, we examined associations
      between enjoyment of PA and participation in both PA and SB in a large sample of
      4th- to 12th-grade US youth. METHODS: A total of 18,930 students from 187 schools
      completed the youth activity profile, a self-report 15-item survey that assesses
      time spent in PA and SB in school and home settings. Two additional items
      captured enjoyment of PA and physical education. Two-way (gender * enjoyment and
      grade * enjoyment) mixed analysis of variances were conducted. RESULTS: Pearson
      correlation results revealed a positive relationship between enjoyment and PA (r
      = .38, P < .05) and an inverse correlation between enjoyment and SB (r = -.23, P
      < .05). Statistically significant main effects of enjoyment were found in the 2
      way analysis of variance for both PA and SB. The simple main effect from analysis
      of variance indicated students with high enjoyment of PA reported higher levels
      of PA and lower levels of SB compared with students reporting moderate or low
      levels of enjoyment. CONCLUSION: The results provide new insights related to the
      relevance of enjoyment as a common underlying variable influencing both PA and SB
      across gender and grade levels.

PMID- 29168423
TI  - Vitamin D levels in children and adolescents with obsessive compulsive disorder.
AB  - BACKGROUND: Recent studies showed that vitamin D deficiency may lead to
      dysfunctional changes in the brain and may be associated with neuropsychiatric
      diseases. AIMS: The present study aims to investigate vitamin D, calcium,
      phosphorus and alkaline phosphatase levels in children and adolescents diagnosed
      with obsessive-compulsive disorder (OCD) and compared them to healthy controls.
      Additionally, the correlation of OCD symptom severity with serum vitamin D level
      will be analyzed. METHODS: A semi-structured interview form (K-SADS-PL) was used
      to diagnose OCD and other comorbidities in accordance with DSM-IV criteria. In
      addition, all participants were assessed with clinical interviews based on DSM-5
      OCD diagnostic criteria. Children's Yale Brown Obsession Compulsion Scale (CY
      BOCS) and Children's Depression Inventory were used in the clinical evaluation.
      RESULTS: Vitamin D levels were lower in patients diagnosed with OCD (15.88 +/-
      6.96 ng/mL) when compared to healthy controls (18.21 +/- 13.24 ng/mL), but the
      difference was not statistically significant (p = .234). Serum calcium, serum
      phosphate and serum alkaline phosphatase levels were not different between the
      groups. A negative correlation was found between serum 25OH-D3 levels and
      obsession scale scores in CY-BOCS. CONCLUSIONS: To our knowledge this is the
      first study that evaluated vitamin D levels in OCD patients without comorbidity.
      The vitamin D levels of newly diagnosed OCD cases were lower but not
      statistically different than healthy controls. Furthermore, the study does also
      not support the presence of a significant association between serum vitamin D
      levels and OCD.

PMID- 29168425
TI  - Scientific Program Schedule 57th Annual Scientific Meeting.

PMID- 29168424
TI  - A prognostic scoring system using inflammatory response biomarkers in oral cavity
      squamous cell carcinoma patients who underwent surgery-based treatment.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of a scoring
      system based on the lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio,
      and platelet-to-lymphocyte ratio for predicting disease-specific survival of oral
      cancer patients treated by surgery. METHODS: From January 2007 to December 2016,
      we retrospectively analyzed data from 69 oral cancer patients who received
      surgery. RESULTS: Lymphocyte-to-monocyte ratio was significantly associated with
      T classification, N classification, and pathologic stage. Neutrophil-to
      lymphocyte ratio was significantly associated with T classification and
      pathologic stage. Platelet-to-lymphocyte ratio was significantly associated with
      N classification and pathologic stage. In multivariate analysis, only a higher
      score on this scoring system was significantly associated with poorer disease
      specific survival. CONCLUSIONS: We found that the prognostic score system based
      on these three values was significantly associated with disease-specific survival
      of oral cancer patients who received surgery, indicating that the prognostic
      scoring system was effective in indirectly predicting systemic inflammatory
      response.

PMID- 29168426
TI  - Interleukin-18 and testosterone levels in men with metabolic syndrome.
AB  - OBJECTIVE: Interleukin 18 (IL-18) is an adipokine associated with obesity. Data
      about the relationship of IL-18 to the metabolic syndrome (MS) are still scarce.
      Low testosterone (T) levels are common in men with MS, but we did not find data
      about the levels of IL-18 in men with low T. The aim of this study was to
      determine the levels of IL-18 in men with MS with or without low T. PATIENTS AND
      METHODS: A total of 251 men were included in the study. Of them 218 had MS (IDF
      2005) and they were divided according to their morning total testosterone (TT)
      level (cutoff 10.4 nmol/l) into two groups: MS-low T (N = 84) and MS-normal T (N
      = 134). The control group consisted of 33 men without MS and low T. IL-18 was
      determined in serum using enzyme-linked immunosorbent assay. A small group of
      eight men with MS and low T levels received testosterone therapy for three months
      and physical and laboratory parameters were monitored at the end of that period.
      RESULTS: MS men were at mean age (+/-SD) = 53.77 +/- 9.59 years; body mass index
      (BMI) = 34.0 +/- 6.3 kg/m2; and TT = 12.59 +/- 5.66 nmol/l. The control group was
      at age = 52.12 +/- 5.2 years (NS); BMI = 25.6 +/- 2.4 kg/m2 (p < .001); and TT =
      17.8 +/- 5.68 nmol/l (p < .001), respectively. The levels of IL-18 were higher in
      the MS group - 345 pg/ml compared to the control one - 264 pg/ml (p < .01). There
      was no significant difference between MS-low T (330.6 pg/ml) and MS-normal T
      (350.2 pg/ml) subgroups. The MS-normal T differed more significantly from the
      control group (p < .001). Significant correlation of testosterone with IL-18
      levels was not found. IL-18 correlated with parameters of obesity, lipids,
      fasting blood sugar (p < .05) and the number of criteria for MS (p < .001). Three
      months on T treatment showed improvement in obesity parameters and only in one
      patient IL-18 had clear reduction while the rest showed no change. CONCLUSIONS:
      In this study, higher IL-18 levels were found in the presence of MS compared to
      healthy men, but they did not differ between men having MS with or without LOH.

PMID- 29168427
TI  - Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2
      negative breast cancer patients, a study from the Danish Breast Cancer
      Cooperative Group (DBCG).
AB  - INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to
      achieve operability in locally advanced breast cancer, and to facilitate breast
      conservation in early breast cancer, particular in patients with highly estrogen
      receptor (ER) positive and HER2-negative disease. Here, we report the results
      obtained by neoadjuvant letrozole in patients with early breast cancer in a phase
      II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER
      positive, HER2-negative operable breast cancer were assigned to four months of
      neoadjuvant letrozole before definitive surgery. Sentinel node or diagnostic fine
      needle aspiration cytology procedure was performed prior to treatment and the
      women were assessed prior, at two months, and before surgery with clinical
      examination, mammography and ultrasonography. Surgical specimens were examined
      for pathological response. Primary outcome was pathological and clinical
      response. RESULTS: The per protocol population consisted of 112 patients.
      Clinical response was evaluated in 109 patients and pathological response in 108.
      Overall a mean decrease in tumor size was 15% (p <= .0001). One patient had
      complete pathological response and 55% of patients had partial pathological
      response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node
      negative status was significantly associated with a better response to NET and
      malignancy grade 3 with a poorer response to NET. One patient progressed during
      treatment and received neoadjuvant chemotherapy. Eight patients received adjuvant
      chemotherapy due to lack of response. CONCLUSION: Neoadjuvant aromatase inhibitor
      therapy is an acceptable strategy in selected postmenopausal patients with ER
      rich and HER2-negative early breast cancer with ductal histology and should be
      considered when chemotherapy either isn't indicated or feasible.

PMID- 29168428
TI  - Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an
      evaluation of inter-observer agreement between pathologists.
AB  - INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor
      infiltrating lymphocytes (TILs) may have clinical utility and may be able to
      direct clinical decisions for subgroups of patients. Clinical utility is,
      however, not sufficient for warranting the implementation of a new biomarker in
      the routine practice, and evaluation of the analytical validity is needed,
      including testing the reproducibility of decentralized assessment of TILs. The
      aim of this study was to evaluate the inter-observer agreement of TILs assessment
      using a standardized method, as proposed by the International TILs Working Group
      2014, applied to a cohort of breast cancers reflecting an average breast cancer
      population. MATERIAL AND METHODS: Stromal TILs were assessed using full slide
      sections from 124 breast cancers with varying histology, malignancy grade and ER-
      and HER2 status. TILs were estimated by nine dedicated breast pathologists using
      scanned hematoxylin-eosin stainings. TILs results were categorized using various
      cutoffs, and the inter-observer agreement was evaluated using the intraclass
      coefficient (ICC), Kappa statistics as well as individual overall agreements with
      the median value of TILs. RESULTS: Evaluation of TILs led to an ICC of 0.71 (95%
      CI: 0.65-0.77) corresponding to an acceptable agreement. Kappa values were in the
      range of 0.38-0.46 corresponding to a fair to moderate agreement. The individual
      agreements increased, when using only two categories ('high' vs. 'low' TILs) and
      a cutoff of 50-60%. DISCUSSION: The results of the present study are in
      accordance with previous studies, and shows that the proposed methodology for
      standardized evaluation of TILs renders an acceptable inter-observer agreement.
      The findings, however, indicate that assessment of TILs needs further refinement,
      and is in support of the latest St. Gallen Consensus, that routine reporting of
      TILs for early breast cancer is not ready for implementation in a clinical
      setting.

PMID- 29168429
TI  - Axillary lymph node dissection in breast cancer patients after sentinel node
      biopsy<sup/>.

PMID- 29168430
TI  - Triple negative breast cancer - prognostic role of immune-related factors: a
      systematic review.
AB  - PURPOSE: Treatment of breast cancer has been increasingly successful in recent
      years with the advent of HER2-receptor targeted treatment and endocrine
      treatment. However, the triple negative subgroup of breast cancer (TNBC)
      (estrogen-, progesterone- and HER2-receptor negative) still lacks targeted
      treatment options. TNBC is a type of breast cancer that often affects younger
      women, and generally has a worse prognosis than other types of breast cancer.
      Recently, the complex role of the immune system in cancer growth, elimination and
      metastasis has been the object of increased attention. There is hope that a more
      detailed understanding of the intricate roles of the constituents of the immune
      system, will hold potential both as prognostic or predictive markers of cancer
      progression, but also as treatment targets for a wide range of tumors, including
      TNBC. The aim of this review is to provide an overview of the cellular immune
      microenvironment in TNBC, and to highlight areas in which TNBC may differ from
      other types of breast cancer. MATERIAL AND METHODS: A search of PubMed was made
      using the terms 'triple negative breast cancer' and 'tumor infiltrating
      lymphocytes', 'CD8', 'CD4', 'B cells', 'natural killer cells', 'macrophages',
      myeloid derived suppressor cells', 'dendritic cells', 'immune check point
      inhibitor', 'CTLA-4' and 'PD-L1'. RESULTS: We find that whilst factors such as
      TILs and certain subgroups of TILs (e.g., CD8 + and regulator T-cells) have been
      extensively researched, none of these markers are currently applicable to routine
      clinical practice. Also, TNBC differs from other types of breast cancer with
      regards to cellular composition of the immune infiltrate and PD-L1 expression,
      and the prognostic significance of these. CONCLUSIONS: Immune-related factors
      have the potential as both prognostic and predictive biomarkers for new
      treatments targeting the immune system in breast cancer. However, multivariate
      analyses, taking other well-known factors into account, are required to determine
      the true value of these biomarkers. Also, differences between TNBC and other
      types of breast cancer may have implications for treatment and use of immune
      related factors as biomarkers.

PMID- 29168432
TI  - Bayesian latent time joint mixed effect models for multicohort longitudinal data.
AB  - Characterization of long-term disease dynamics, from disease-free to end-stage,
      is integral to understanding the course of neurodegenerative diseases such as
      Parkinson's and Alzheimer's, and ultimately, how best to intervene. Natural
      history studies typically recruit multiple cohorts at different stages of disease
      and follow them longitudinally for a relatively short period of time. We propose
      a latent time joint mixed effects model to characterize long-term disease
      dynamics using this short-term data. Markov chain Monte Carlo methods are
      proposed for estimation, model selection, and inference. We apply the model to
      detailed simulation studies and data from the Alzheimer's Disease Neuroimaging
      Initiative.

PMID- 29168434
TI  - Changes in knee shape and geometry resulting from total knee arthroplasty.
AB  - Changes in knee shape and geometry resulting from total knee arthroplasty can
      affect patients in numerous important ways: pain, function, stability, range of
      motion, and kinematics. Quantitative data concerning these changes have not been
      previously available, to our knowledge, yet are essential to understand
      individual experiences of total knee arthroplasty and thereby improve outcomes
      for all patients. The limiting factor has been the challenge of accurately
      measuring these changes. Our study objective was to develop a conceptual
      framework and analysis method to investigate changes in knee shape and geometry,
      and prospectively apply it to a sample total knee arthroplasty population. Using
      clinically available computed tomography and radiography imaging systems, the
      three-dimensional knee shape and geometry of nine patients (eight varus and one
      valgus) were compared before and after total knee arthroplasty. All patients had
      largely good outcomes after their total knee arthroplasty. Knee shape changed
      both visually and numerically. On average, the distal condyles were slightly
      higher medially and lower laterally (range: +4.5 mm to -4.4 mm), the posterior
      condyles extended farther out medially but not laterally (range: +1.8 to -6.4
      mm), patellofemoral distance increased throughout flexion by 1.8-3.5 mm, and
      patellar thickness alone increased by 2.9 mm (range: 0.7-5.2 mm). External
      femoral rotation differed preop and postop. Joint line distance, taking cartilage
      into account, changed by +0.7 to -1.5 mm on average throughout flexion. Important
      differences in shape and geometry were seen between pre-total knee arthroplasty
      and post-total knee arthroplasty knees. While this is qualitatively known, this
      is the first study to report it quantitatively, an important precursor to
      identifying the reasons for the poor outcome of some patients. Using the
      developed protocol and visualization techniques to compare patients with good
      versus poor clinical outcomes could lead to changes in implant design, implant
      selection, component positioning, and surgical technique. Recommendations based
      on this sample population are provided. Intraoperative and postoperative feedback
      could ultimately improve patient satisfaction.

PMID- 29168431
TI  - Nucleolin phosphorylation regulates PARN deadenylase activity during cellular
      stress response.
AB  - Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that
      controls gene expression by regulating either mRNA stability and/or translation.
      NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates
      miRNA functions in the nearby target sequences, and regulates mRNA deadenylation.
      However, the mechanism by which NCL phosphorylation affects these functions and
      the identity of the deadenylase involved, remain largely unexplored. Earlier we
      demonstrated that NCL phosphorylation is vital for cell cycle progression and
      proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites
      confers dominant-negative effect on proliferation by increasing p53 expression,
      possibly mimicking cellular DNA damage conditions. In this study, we show that
      NCL phosphorylation at those CK2 consensus sites in the N-terminus is necessary
      to induce deadenylation upon oncogenic stimuli and UV stress. NCL-WT, but not
      hypophosphorylated NCL-6/S*A, activates poly (A)-specific ribonuclease (PARN)
      deadenylase activity. We further demonstrate that NCL interacts directly with
      PARN, and under non-stress conditions also forms (a) complex (es) with factors
      that regulate deadenylation, such as p53 and the ARE-binding protein HuR. Upon UV
      stress, the interaction of hypophosphorylated NCL-6/S*A with these proteins is
      favored. As an RNA-binding protein, NCL interacts with PARN deadenylase
      substrates such as TP53 and BCL2 mRNAs, playing a role in their downregulation
      under non-stress conditions. For the first time, we show that NCL phosphorylation
      offers specificity to its protein-protein, protein-RNA interactions, resulting in
      the PARN deadenylase regulation, and hence gene expression, during cellular
      stress responses.

PMID- 29168436
TI  - Intersections between gender and other relevant social determinants of health
      inequalities.

PMID- 29168435
TI  - A continuous assay for monitoring the synthetic and proofreading activities of
      multiple aminoacyl-tRNA synthetases for high-throughput drug discovery.
AB  - Aminoacyl-tRNA synthetases (aaRSs) catalyze the aminoacylation of tRNAs to
      produce the aminoacyl-tRNAs (aa-tRNAs) required by ribosomes for translation of
      the genetic message into proteins. To ensure the accuracy of tRNA aminoacylation,
      and consequently the fidelity of protein synthesis, some aaRSs exhibit a
      proofreading (editing) site, distinct from the aa-tRNA synthetic site. The aaRS
      editing site hydrolyzes misacylated products formed when a non-cognate amino acid
      is used during tRNA charging. Because aaRSs play a central role in protein
      biosynthesis and cellular life, these proteins represent longstanding targets for
      therapeutic drug development to combat infectious diseases. Most existing aaRS
      inhibitors target the synthetic site, and it is only recently that drugs
      targeting the proofreading site have been considered. In the present study, we
      developed a robust assay for the high-throughput screening of libraries of
      inhibitors targeting both the synthetic and the proofreading sites of up to four
      aaRSs simultaneously. Thus, this assay allows for screening of eight distinct
      enzyme active sites in a single experiment. aaRSs from several prominent human
      pathogens (i.e., Mycobacterium tuberculosis, Plasmodium falciparum, and
      Escherichia coli) were used for development of this assay.

PMID- 29168437
TI  - High-ACE Low Wage Workers: Occupational Health Nursing Research and Praxis
      Through a Trauma-Informed Lens.
AB  - Individuals with a history of adverse childhood experiences (ACEs)
      disproportionately have poor mental and physical health outcomes. These
      experiences affect individuals across the life span extending beyond health with
      deleterious impact on work-related outcomes. Low-wage workers are particularly at
      risk. Social service and health organizations are becoming aware of the extent to
      which the populations they serve have been affected by these experiences.
      Employment support programs may serve high-ACE individuals but likely are unaware
      of their histories and the developmental or health deficits that result and can
      impinge on successful employment. Occupational health nurses may be well
      positioned not only to implement trauma-informed care in workplaces but also to
      influence the ways in which employment services for this vulnerable group are
      delivered. The purpose of this article is to consider how ACEs could affect
      vulnerable workers. The need for trauma-informed research and praxis to advance
      occupational health nursing is discussed.

PMID- 29168438
TI  - IMPACT OF SEX COMPOSITION OF LIVING CHILDREN AND COUPLES' AGREEMENT ON SUBSEQUENT
      FERTILITY IN INDIA.
AB  - SummaryThe desire for children could be considered a reliable predictor of
      subsequent fertility. At the same time, the sex composition of surviving
      children, along with other demographic and socioeconomic factors, may affect a
      couple's fertility desire and, therefore, their subsequent fertility. This study
      examined the impact of the sex composition of living children and a couple's
      agreement on fertility desire on their subsequent fertility in India using data
      came from two rounds of nationally representative surveys: the India Human
      Development Survey (IHDS)-I (2004-05) and IHDS-II (2011-12). To understand which
      factors affect the chances of an additional pregnancy or childbirth, a random
      effects logistic regression model was applied to the panel data. It was found
      that the fertility desires of both marital partners were important in determining
      the chances of subsequent fertility. About 35% of the couples wanting to limit
      children had undergone pregnancy or childbirth, while 76% of the couples wanting
      more children had conceived or given birth to children. In the case of
      discordance between the spouses, subsequent fertility was found to remain
      intermediate between those agreeing to continue childbirth and those wanting to
      limit it. The findings also affirmed that child sex preference, specifically son
      preference, still persists in Indian society. More than 80% of the couples with
      only daughters in IHDS-I mutually wanted to have additional children, whereas in
      families that only had sons, the chance of a subsequent pregnancy was inversely
      associated with the number of sons. Strong patriarchal settings, combined with
      cultural and socioeconomic factors, affect the persistence of sex preference in
      India. Programmes aimed at increasing family planning use need to address son
      preference and should include components that promote the value of girl children.

PMID- 29168440
TI  - WOMEN'S EMPOWERMENT AND GENDER INEQUALITY IN ADOLESCENT NUTRITIONAL STATUS:
      EVIDENCE FROM THE INDONESIAN FAMILY LIFE SURVEY.
AB  - SummaryIn contrast to the extensive knowledge on the association between women's
      empowerment and the nutritional status of children under the age of five,
      relatively little is known about the influence of women's empowerment on
      adolescents' nutritional status. This study aimed to assess the association
      between women's empowerment and gender inequalities in adolescent nutritional
      status. Data were from the Indonesian Family Life Survey (IFLS) covering the
      period 1997 to 2015, and consisted of 16,683 observations from 13,396 adolescents
      between the ages of 10 and 19 years born in 6781 families. Three indicators of
      women's empowerment were used: mother's education, mother's bargaining power and
      mother's working status. Multivariate linear regression with robust standard
      errors was used to examine whether and how these indicators of women's
      empowerment influenced adolescent nutritional status. Interaction terms were
      added to analyse how the association between women's empowerment and adolescent
      nutritional status differed by gender. The results showed that mother's education
      and mother's working status were significantly associated with adolescent
      nutritional status, particularly with height-for-age. Adolescents of well
      educated mothers had a higher height-for-age while those who were raised by
      mothers with a blue-collar job had a lower height-for-age. Although no gender
      differences were found for height-for-age, gender differences for BMI-for-age
      were obvious, with boys having a lower BMI-for-age than girls. Interactions
      between indicators of mother's empowerment and gender showed that the gender gap
      in BMI-for-age was smaller for adolescents of more educated mothers. However,
      further analyses of food consumption patterns showed that boys whose mothers were
      more educated consumed more fast food and had higher instant noodle consumption
      than girls, thus suggesting gender bias in new disguise.

PMID- 29168439
TI  - Drivers of measles mortality: the historic fatality burden of famine in
      Bangladesh.
AB  - Measles is a major cause of childhood morbidity and mortality in many parts of
      the world. Estimates of the case-fatality rate (CFR) of measles have varied
      widely from place to place, as well as in the same location over time. Amongst
      populations that have experienced famine or armed conflict, measles CFR can be
      especially high, although past work has mostly focused on refugee populations.
      Here, we estimate measles CFR between 1970 and 1991 in a rural region of
      Bangladesh, which experienced civil war and famine in the 1970s. We use
      historical measles mortality data and a mechanistic model of measles transmission
      to estimate the CFR of measles. We first demonstrate the ability of this model to
      recover the CFR in the absence of incidence data, using simulated mortality data.
      Our method produces CFR estimates that correspond closely to independent
      estimates from surveillance data and we can capture both the magnitude and the
      change in CFR suggested by these previous estimates. We use this method to
      quantify the sharp increase in CFR that resulted in a large number of deaths
      during a measles outbreak in the region in 1976. Most of the children who died
      during this outbreak were born during a famine in 1974, or in the 2 years
      preceding the famine. Our results suggest that the period of turmoil during and
      after the 1971 war and the sustained effects of the famine, is likely to have
      contributed to the high fatality burden of the 1976 measles outbreak in Matlab.

PMID- 29168441
TI  - Detection of HEV-specific antibodies in four non-human primate species, including
      great apes, from different zoos in Germany.
AB  - The hepatitis E virus (HEV) has been described in humans and various animal
      species in different regions of the world. However, the knowledge on natural HEV
      infection in non-human primates and the corresponding risk of zoonotic
      transmission is scarce. To determine whether primates in captivity are affected
      by HEV infection, we investigated 259 individual sera of clinically healthy non
      human primates of 14 species from nine German zoos. Using a commercial double
      antigen-sandwich ELISA and a commercial IgG ELISA, 10 animals (3.9%) reacted
      positive in at least one assay. Three ape species and one Old World monkey
      species were among the seropositive animals: bonobo (Pan paniscus), gorilla
      (Gorilla gorilla gorilla), lar gibbon (Hylobates lar) and drill (Mandrillus
      leucophaeus). Testing for anti-HEV-IgM antibodies by commercial ELISA and for
      viral RNA by reverse-transcription real-time polymerase chain reaction resulted
      in negative results for all animals indicating the absence of acute HEV
      infections. In the past, no clinical signs of hepatitis were recorded for the
      seropositive animals. The results suggest that non-human primates in zoos can get
      naturally and subclinically infected with HEV or related hepeviruses. Future
      studies should evaluate potential sources and transmission routes of these
      infections and their impact on human health.

PMID- 29168442
TI  - Seasonality of urinary tract infections in the United Kingdom in different age
      groups: longitudinal analysis of The Health Improvement Network (THIN).
AB  - Evidence regarding the seasonality of urinary tract infection (UTI) consultations
      in primary care is conflicting and methodologically poor. To our knowledge, this
      is the first study to determine whether this seasonality exists in the UK,
      identify the peak months and describe seasonality by age. The monthly number of
      UTI consultations (N = 992 803) and nitrofurantoin and trimethoprim prescriptions
      (N = 1 719 416) during 2008-2015 was extracted from The Health Improvement
      Network (THIN), a large nationally representative UK dataset of electronic
      patient records. Negative binomial regression models were fitted to these data to
      investigate seasonal fluctuations by age group (14-17, 18-24, 25-45, 46-69, 70
      84, 85+) and by sex, accounting for a change in the rate of UTI over the study
      period. A September to November peak in UTI consultation incidence was observed
      for ages 14-69. This seasonality progressively faded in older age groups and no
      seasonality was found in individuals aged 85+, in whom UTIs were most common.
      UTIs were rare in males but followed a similar seasonal pattern than in females.
      We show strong evidence of an autumnal seasonality for UTIs in individuals under
      70 years of age and a lack of seasonality in the very old. These findings should
      provide helpful information when interpreting surveillance reports and the
      results of interventions against UTI.

PMID- 29168444
TI  - Prevalence and molecular identification of Trichinella species isolated from
      wildlife originating from Limpopo and Mpumalanga provinces of South Africa.
AB  - Trichinella species are widely distributed on all continents with the exception
      of Antarctica, although the full spectrum of Trichinella species found in sub
      Saharan African countries, and their hosts, has not been fully documented. This
      study was conducted to determine the prevalence of Trichinella in wildlife from
      the Greater Kruger National Park (GKNP) and adjacent areas located in the Limpopo
      and Mpumalanga provinces of South Africa, and to identify the species and/or
      genotypes of Trichinella larvae isolated from muscle tissues, using molecular
      techniques. A review of Trichinella spp. and their wildlife hosts reported during
      1964-2011 was also conducted and the results were compared with our current
      study. Ninety samples representing 15 mammalian, two bird and three reptile
      species were screened for Trichinella infection during 2012-2016, using
      artificial digestion. Isolates detected were identified using a multiplex
      polymerase chain reaction (PCR) amplification of the internal transcriber spacers
      ITS1 and ITS2, and expansion segment V (ESV) regions of ribosomal DNA, followed
      by molecular analysis of the sequences. Twenty samples from seven wildlife
      species were positive for Trichinella spp. larvae, with an overall prevalence of
      21.1% (20/90). The prevalence was higher in carnivores (18.9%, 18/90) than in
      omnivores (2.2%, 2/90). Analysis of sequences showed that eight of the isolates -
      two from spotted hyaena (Crocuta crocuta) (2/8), three from lion (Panthera leo)
      (3/13), one from leopard (Panthera pardus) (1/6), one from small spotted genet
      (Genetta genetta) (1/2) and one Nile monitor lizard (Varanus niloticus) (1/2) -
      conformed to Trichinella zimbabwensis. One isolate from a hyaena was grouped
      under the encapsulated species clade comprising T. nelsoni and genotype
      Trichinella T8 reported to be present in South Africa. This is the first report
      confirming natural infection by T. zimbabwensis in hyaena, leopard, genet and
      Nile monitor lizard, adding to the body of knowledge on the epidemiology of
      Trichinella infections in the Greater Kruger National Park of South Africa. Ten
      Trichinella-like larval isolates recovered after digestion from four wildlife
      species in this study (2012-2016) revealed inconclusive results due to DNA
      degradation resulting from poor storage or too few larvae for analysis, in
      comparison to 20 unidentified isolates from five wildlife species during the 1964
      2011 period.

PMID- 29168443
TI  - Francisella tularensis in muscle from diseased hares - a risk factor for humans?
AB  - Tularemia caused by the bacterium Francisella tularensis is a zoonotic disease.
      Tularemia is a common disease in the hare, and as a game species can be an
      important source of infection for humans. In this study, hares diagnosed with
      tularemia were examined with the aim to investigate whether the muscle (meat) had
      any pathological changes and/or contained F. tularensis. Real-time PCR and/or
      immunohistochemistry (IHC) detected the bacteria in muscle samples from 40 out of
      43 investigated hares. IHC showed that bacteria were few and most commonly
      located in the peri- and endomysium. Histopathology showed occasional perimysial
      necroses and mild inflammation in association to the bacteria. Attempts to
      culture from 14 muscle samples were successful in two cases, both stored in the
      freezer <1 year. The result of this study shows that since F. tularensis is
      present in the muscle of infected hares, there is a risk for human infection when
      consuming undercooked hare meat. The risk is enhanced by the fact that some hares
      do not have easily detected gross lesions. The study contributes to a better
      understanding of sources of infection and risk factors for humans to contract
      tularemia.

PMID- 29168445
TI  - Strengthened Ebola surveillance in France during a major outbreak in West Africa:
      March 2014-January 2016.
AB  - : Introduction An unprecedented outbreak of Ebola virus diseases (EVD) occurred
      in West Africa from March 2014 to January 2016. The French Institute for Public
      Health implemented strengthened surveillance to early identify any imported case
      and avoid secondary cases. METHODS: Febrile travellers returning from an affected
      country had to report to the national emergency healthcare hotline. Patients
      reporting at-risk exposures and fever during the 21st following day from the last
      at-risk exposure were defined as possible cases, hospitalised in isolation and
      tested by real-time polymerase chain reaction. Asymptomatic travellers reporting
      at-risk exposures were considered as contact and included in a follow-up protocol
      until the 21st day after the last at-risk exposure. RESULTS: From March 2014 to
      January 2016, 1087 patients were notified: 1053 were immediately excluded because
      they did not match the notification criteria or did not have at-risk exposures;
      34 possible cases were tested and excluded following a reliable negative result.
      Two confirmed cases diagnosed in West Africa were evacuated to France under
      stringent isolation conditions. Patients returning from Guinea (n = 531; 49%) and
      Mali (n = 113; 10%) accounted for the highest number of notifications.
      CONCLUSION: No imported case of EVD was detected in France. We are confident that
      our surveillance system was able to classify patients properly during the
      outbreak period.

PMID- 29168446
TI  - A Randomized Trial of Two Cover Gowns Comparing Contamination of Healthcare
      Personnel During Removal of Personal Protective Equipment.
AB  - In a randomized trial, a gown designed to allow easy removal at the neck and with
      increased skin coverage and snugness of fit at the wrist significantly reduced
      contamination of personnel during personal protective equipment (PPE) removal.
      Our results suggest that simple modifications of PPE can reduce contamination of
      personnel. Infect Control Hosp Epidemiol 2018;39:97-100.

PMID- 29168447
TI  - A brief summary of the epidemiology and genetic relatedness of avian influenza
      H9N2 virus in birds and mammals in the Middle East and North Africa.
AB  - H9N2 is the most widespread avian influenza virus subtype in poultry worldwide.
      It infects a broad spectrum of host species including birds and mammals.
      Infections in poultry and humans vary from silent to fatal. Importantly, all AIV,
      which are fatal in humans (e.g. H5N1, H7N9) acquired their 'internal' gene
      segments from H9N2 viruses. Although H9N2 is endemic in the Middle East (ME) and
      North Africa since the late 1990s, little is known about its epidemiology and
      genetics on a regional level. In this review, we summarised the epidemiological
      situation of H9N2 in poultry and mammals in Iran, Iraq, Kuwait, Qatar, United
      Arab Emirates, Oman, Bahrain, Yemen, Saudi Arabia, Jordan, Palestine, Israel,
      Syria, Lebanon, Turkey, Egypt, Sudan, Libya, Tunisia, Algeria and Morocco. The
      virus has been isolated from humans in Egypt and serosurveys indicated widespread
      infection particularly among poultry workers and pigs in some countries. Some
      isolates replicated well in experimentally inoculated dogs, mice, hamsters and
      ferrets. Insufficient protection of immunised poultry was frequently reported
      most likely due to concurrent viral or bacterial infections and antigenic drift
      of the field viruses from outdated vaccine strains. Genetic analysis indicated
      several distinct phylogroups including a panzootic genotype in the Asian and
      African parts of the ME, which may be useful for the development of vaccines. The
      extensive circulation of H9N2 for about 20 years in this region where the H5N1
      virus is also endemic in some countries, poses a serious public health threat.
      Regional surveillance and control strategy are highly recommended.

PMID- 29168448
TI  - A competitive enzyme-linked immunosorbent assay for rapid detection of antibodies
      against Trichinella spiralis and T. britovi - one test for humans and swine.
AB  - Infection with parasites from the Trichinella genus occurs in many vertebrates
      but disease only occurs in humans (trichinellosis). Humans are infected after the
      consumption of raw or undercooked meat from infected wild or domestic animals
      (usually swine or horses). Using the monoclonal antibody (mAb) 7C2C5, specific
      for an epitope unique to the muscle larvae of the genus Trichinella, we have
      developed a competitive enzyme-linked immunosorbent assay (c-ELISA) that enables
      the rapid detection of Trichinella-specific antibodies in sera originating from
      two different host species (human, swine) infected with either Trichinella
      spiralis or Trichinella britovi. This novel c-ELISA exhibited 100% specificity
      and sensitivity, as confirmed by a Western blot test. The assay is easy to use
      (one incubation step), and the time required for the procedure (45 min) is
      shorter than in any other ELISA format. This test could be useful for both the
      detection and surveillance of Trichinella infections.

PMID- 29168449
TI  - Barcoding in trypanosomes.
AB  - Trypanosomes (genus Trypanosoma) are parasites of humans, and wild and domestic
      mammals, in which they cause several economically and socially important
      diseases, including sleeping sickness in Africa and Chagas disease in the
      Americas. Despite the development of numerous molecular diagnostics and
      increasing awareness of the importance of these neglected parasites, there is
      currently no universal genetic barcoding marker available for trypanosomes. In
      this review we provide an overview of the methods used for trypanosome detection
      and identification, discuss the potential application of different barcoding
      techniques and examine the requirements of the 'ideal' trypanosome genetic
      barcode. In addition, we explore potential alternative genetic markers for
      barcoding Trypanosoma species, including an analysis of phylogenetically
      informative nucleotide changes along the length of the 18S rRNA gene.

PMID- 29168450
TI  - Estimates of the burden of illness for eight enteric pathogens associated with
      animal contact in Canada.
AB  - Enteric pathogens are commonly known to be transmitted through food or water;
      however, contact with animals is another important transmission route. This study
      estimated the annual burden of illness attributable to animal contact for eight
      enteric pathogens in Canada. Using data from a Canadian expert elicitation on
      transmission routes, the proportion of enteric illnesses attributable to animal
      contact was estimated for each pathogen to estimate the annual number of
      illnesses, hospitalizations and deaths in Canada. For each estimate, a mean and
      probability intervals were generated. Of all illnesses caused by these eight
      pathogens, 16% were estimated attributable to animal contact. This estimate
      translates to 86 000 (31 000-166 000) illnesses, 488 (186-890) hospitalizations
      and 12 (2-28) deaths annually for the eight pathogens combined. Campylobacter
      spp. is the leading cause of illnesses annually, with an estimated 38 000 (14 000
      71 000) illnesses occurring each year, followed by non-typhoidal Salmonella spp.
      (17 000, 6000-32 000). The majority of hospitalizations were attributable to non
      typhoidal Salmonella spp. (36%) and Campylobacter spp. (31%). Non-typhoidal
      Salmonella spp. (28%) and Listeria monocytogenes (31%) were responsible for the
      majority of the estimated deaths. These results identify farm animal and pet/pet
      food exposure as key pathways of transmission for several pathogens. The
      estimated burden of illness associated with animal contact is substantial.

PMID- 29168451
TI  - Intraindividual Cognitive Variability: An Examination of ANAM4 TBI-MIL Simple
      Reaction Time Data from Service Members with and without Mild Traumatic Brain
      Injury.
AB  - OBJECTIVES: The Automated Neuropsychological Assessment Metrics 4 TBI-MIL (ANAM4)
      is a computerized cognitive test often used in post-concussion assessments with
      U.S. service members (SMs). However, existing evidence remains mixed regarding
      ANAM4's ability to identify cognitive issues following mild traumatic brain
      injury (mTBI). Studies typically examine ANAM4 using standardized scores and/ or
      comparisons to a baseline. A more fine-grained approach involves examining
      inconsistency within an individual's performance (i.e., intraindividual
      variability). METHODS: Data from 237 healthy control SMs and 105 SMs within seven
      days of mTBI who took the ANAM4 were included in analyses. Using each
      individual's raw scores on a simple reaction time (RT) subtest (SRT1) that is
      repeated at the end of the battery (SRT2), we calculated mean raw RT and the
      intraindividual standard deviation (ISD) of trial-by-trial RT. Analyses
      investigated differences between groups in mean RT, RT variability (i.e., ISD),
      and change in ISD from SRT1 and SRT2. RESULTS: Using regression residuals to
      control for demographic variables, analysis of variance, and pairwise comparisons
      revealed the control group had faster mean RT and smaller ISD compared to the
      mTBI group. Furthermore, the mTBI group had a significant increase in ISD from
      SRT1 to SRT2, with effect sizes exceeding the minimum practical effect for
      comparisons of ISD in SRT2 and change in ISD from SRT1 to SRT2. CONCLUSIONS:
      While inconsistencies in performance are often viewed as test error, the results
      suggest intraindividual cognitive variability may be more sensitive than
      traditional metrics in detecting changes in cognitive function after mTBI.
      Additionally, the findings highlight the utility of the ANAM4's repeating a RT
      subtest at two points in the same session for exploring within-subject
      differences in performance variability. (JINS, 2018, 24, 156-162).

PMID- 29168452
TI  - Third-trimester tenofovir to prevent mother-to-child hepatitis B virus
      transmission.

PMID- 29168453
TI  - Role of primary care in the management of schizophrenia.

PMID- 29168454
TI  - Minimalistic immunohistochemical approach to non-small cell carcinoma of the lung
      in small biopsies in the context of the 2015 WHO Classification of Lung Cancer.

PMID- 29168455
TI  - Molecular epidemiology of tuberculosis: Opportunities & challenges in disease
      control.

PMID- 29168456
TI  - Shifting gears from embryonic to very small embryonic-like stem cells for
      regenerative medicine.

PMID- 29168457
TI  - Newer direct-acting antivirals for hepatitis C virus infection: Perspectives for
      India.
AB  - Approximately three per cent of the world's population (170-200 million people)
      is chronically infected with hepatitis C virus (HCV) and almost 500,000 people
      die each year (mostly in lower middle-income countries) from complications
      secondary to HCV infection. In India, HCV infection imposes a considerable burden
      of mortality, morbidity and healthcare costs. In the last two decades, the
      treatment of HCV has evolved from interferon (IFN)-based therapies with or
      without ribavirin (RBV) to pegylated-IFN (PEG-IFN) and RBV-based therapies that
      were better tolerated by patients. However, the introduction of oral drugs, which
      specifically target virus-specific proteins, has now revolutionized the treatment
      of chronic HCV. These agents are known as direct-acting antivirals (DAAs). These
      drugs have resulted in very high HCV cure rates even with reduced treatment
      duration and an excellent tolerability by the patients compared to PEG-IFN- and
      RBV-based therapies. In India, sofosbuvir (SOF), one of the most effective DAAs,
      has been made available at a compassionate price; thus only those DAA-based
      management strategies, which contain SOF are adopted in India. Here, we review
      different DAAs and their possible roles in different genotypes and stages of
      liver disease, stressing upon the role of SOF. An attempt has also been made to
      devise strategies using SOF for the most prevalent genotypes in our country
      (genotypes 3 and 1) and cirrhosis.

PMID- 29168458
TI  - Antipsychotic treatment, psychoeducation & regular follow up as a public health
      strategy for schizophrenia: Results from a prospective study.
AB  - BACKGROUND & OBJECTIVES: In low- and middle-income countries such as India, a
      feasible public health strategy could be to ensure continuous antipsychotics and
      psychoeducation for those with schizophrenia. Whether such a strategy favourably
      influences its course and outcome is not well-studied. The objectives of this
      study were to examine these issues in a cohort of patients with schizophrenia in
      a rural south Indian taluk (an administrative block). This cohort was part of a
      community intervention programme running in the place since the past one decade.
      METHODS: A total of 201 patients were assessed after an average of four years of
      follow up. Psychopathology, disability and course of illness were assessed using
      Positive and Negative Syndrome Scale (PANSS), Indian Disability Evaluation and
      Assessment Scale (IDEAS) and Psychiatric and Personal History Schedule (PPHS),
      respectively. Interventions included ensuring continuous antipsychotic treatment
      and low-intensity psychoeducation. RESULTS: One hundred and forty two [70.6%; 95%
      confidence interval (CI): 64.35-76.95] of the 201 patients achieved clinical
      remission by the end of follow up period (four years); 140 (69.6%; 95% CI: 63.29
      76.07) had satisfactory outcome (42.3% best outcome and 27.4% intermediate
      outcome). There was a significant reduction in the proportion of patients with
      disability [134/201 (66.7%) at baseline; 55/201 (27.3%) at follow up;
      PInterpretation & conclusions: Treatment with antipsychotics and psychoeducation
      can favourably influence the course of schizophrenia and reduce disability in a
      substantial proportion of patients. Structured psychosocial interventions may be
      indicated in the significant minority who show suboptimal outcome with this
      strategy.

PMID- 29168459
TI  - p40 & thyroid transcription factor-1 immunohistochemistry: A useful panel to
      characterize non-small cell lung carcinoma-not otherwise specified (NSCLC-NOS)
      category.
AB  - BACKGROUND & OBJECTIVES: Accurate histopathological subtyping of non-small cell
      lung carcinoma (NSCLC) is essential for targeted therapeutic agents.
      Immunohistochemistry (IHC) is helpful in identification of different tumour
      subtypes. In this study two marker approaches, one each for glandular and
      squamous cell differentiation was applied to maximize the proportion of
      accurately subtyped NSCLC not otherwise specified (NOS) tumours on small biopsy
      samples. METHODS: Two hundred and sixty three consecutive lung biopsies of
      primary lung carcinoma were prospectively studied. These were subtyped first
      morphologically and then by IHC for p40 and thyroid transcription factor-1 (TTF
      1). The diagnosis of NSCLC-NOS before and after addition of IHC was evaluated.
      Results were correlated and validated with morphologically proven cases and
      matched surgical specimens. RESULTS: Based on morphology, only 140 of the 263
      (53.2%) cases of NSCLC were characterized, whereas 123 (46.7%) were classified as
      NSCLC-NOS type. With addition of IHC (p40 and TTF-1), the latter category reduced
      to 14.4 per cent and a sum of 225 (85.5%) cases were accurately subtyped into
      squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma. p40 showed
      100 per cent sensitivity and specificity for squamous differentiation whereas TTF
      1 showed sensitivity of 85.3 per cent and specificity of 98.1 per cent. Ninety
      per cent correlation of morphologic subtypes was achieved with matched resected
      specimens. INTERPRETATION & CONCLUSIONS: Our results showed that an approach of
      using only a two-antibody panel (p40 and TTF-1) might help in reduction of
      diagnostic category of NSCLC-NOS significantly and contribute in saving tissue
      for future molecular testing.

PMID- 29168460
TI  - Molecular & genetic characteristics of Mycobacterium tuberculosis strains
      circulating in the southern part of West Siberia.
AB  - BACKGROUND & OBJECTIVES: A complicated epidemiological situation characterized by
      significantly high tuberculosis (TB) morbidity is observed in West Siberia. This
      study was aimed to investigate the genetic characteristics of Mycobacterium
      tuberculosis circulating in the southern part of West Siberia (in the Omsk
      region). METHODS: From March 2013 to January 2015, 100 isolates of M.
      tuberculosis were obtained from patients with pulmonary TB living in the Omsk
      region. Drug susceptibility testing was performed on Lowenstein-Jensen medium
      (absolute concentration method). Genetic typing of isolates was carried out by
      variable number tandem repeats of mycobacterial interspersed repetitive units
      (MIRU-VNTR) typing and polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis. The genetic types and characteristics of
      cluster strains were determined using 15 MIRU-VNTR loci. RESULTS: Thirty six VNTR
      types were found. Twenty six (26.0%) isolates had a unique profile, and the
      remaining 74 were grouped in 10 clusters containing from 2 to 23 isolates. The
      Beijing genotype was found in 72 isolates, 61 (85.0%) of which were part of five
      clusters that included two large clusters containing 23 isolates. Other genetic
      families, such as Latin-American Mediterranean (LAM, 11.0%), S family (2.0%) and
      Haarlem (4.0%), were also detected. The genetic family of 11 isolates could not
      be determined. Six different VNTR profiles were found in these non-classified
      isolates. Only 16 per cent of isolates were sensitive to anti-TB drugs. The
      katG315 (94.8%) and rpoB531 (92.2%) mutations were identified in 77 multidrug
      resistant M. tuberculosis isolates. INTERPRETATION & CONCLUSIONS: This study
      showed that the M. tuberculosis population in the Omsk region was heterogeneous.
      The Beijing genotype predominated and was actively spreading. The findings
      obtained point to the need for the implementation of more effective preventive
      measures to stop the spread of drug-resistant M. tuberculosis strains.

PMID- 29168461
TI  - Study of stem cell homing & self-renewal marker gene profile of ex vivo expanded
      human CD34+ cells manipulated with a mixture of cytokines & stromal cell-derived
      factor 1.
AB  - BACKGROUND & OBJECTIVES: Next generation transplantation medicine aims to develop
      stimulating cocktail for increased ex vivo expansion of primitive hematopoietic
      stem and progenitor cells (HSPC). The present study was done to evaluate the
      cocktail GF (Thrombopoietin + Stem Cell factor + Flt3-ligand) and homing-defining
      molecule Stromal cell-derived factor 1 (SDF1) for HSPC ex vivo expansion.
      METHODS: Peripheral blood stem cell (n=74) harvests were analysed for
      CD34hiCD45lo HSPC. Immunomagnetically enriched HSPC were cultured for eight days
      and assessed for increase in HSPC, colony forming potential in vitro and in vivo
      engrafting potential by analyzing human CD45+ cells. Expression profile of genes
      for homing and stemness were studied using microarray analysis. Expression of
      adhesion/homing markers were validated by flow cytometry/ confocal microscopy.
      RESULTS: CD34hiCD45lo HSPC expansion cultures with GF+SDF1 demonstrated increased
      nucleated cells (n=28, P+ cells (n=8, P=0.021) and increased colony forming units
      (cfu) compared to unstimulated and GF-stimulated HSPC. NOD-SCID mice transplanted
      with GF+SDF1-HSPC exhibited successful homing/engraftment (n=24, PInterpretation
      & conclusions: Cocktail of cytokines and SDF1 showed good potential to
      successfully expand HSPC which exhibited enhanced ability to generate
      multilineage cells in short-term and long-term repopulation assay. This cocktail
      mediated stem cell expansion has potential to obviate the need for longer and
      large volume apheresis procedure making it convenient for donors.

PMID- 29168462
TI  - Potential benefit of optimizing atrioventricular & interventricular delays in
      patients with cardiac resynchronization therapy.
AB  - BACKGROUND & OBJECTIVES: The clinical benefit of optimization (OPT) of
      atrioventricular delay (AVD) and interventricular delay (VVD) in cardiac
      resynchronization therapy (CRT) remains debatable. This study was aimed to
      determine the influence of AVD and VVD OPT on selected parameters in patients
      early after CRT implantation and at mid-term follow up (FU). METHODS: Fifty two
      patients (61+/-10 yr, 23 males) with left bundle branch block, left ventricular
      ejection fraction (LVEF) <=35 per cent and heart failure were selected for CRT
      implantation. Early on the second day (2DFU) after CRT implantation, the patients
      were assigned to the OPT or the factory setting (FS) group. Haemodynamic and
      electrical parameters were evaluated at baseline, on 2DFU after CRT and mid-term
      FU [three-month FU (3MFU)]. Echocardiographic measures were assessed before
      implantation and at 3MFU. The AVD/VVD was deemed optimal for the highest cardiac
      output (CO) with impedance cardiography (ICG) monitoring. RESULTS: On 2DFU, the
      AVD was shorter in the OPT group, LV was paced earlier than in FS group and CO
      was insignificantly higher in OPT group. At 3MFU, improvement of CO was observed
      only in OPT patients, but the intergroup difference was not significant. At 3MFU
      in OPT group, reduction of LV in terms of LV end-diastolic diameter (LVeDD), LV
      end-systolic diameter, LV end-diastolic and systolic volume with the improvement
      in LVEF was observed. In FS group, only a reduction in LVeDD was present. In OPT
      group, the paced QRS duration was shorter than in FS group patients.
      INTERPRETATION & CONCLUSIONS: CRT OPT of AVD and VVD with ICG was associated with
      a higher CO and better reverse LV remodelling. CO monitoring with ICG is a
      simple, non-invasive tool to optimize CRT devices.

PMID- 29168463
TI  - A preliminary study of natural history of mild traumatic brain injury by using
      multidimensional approach.
AB  - BACKGROUND & OBJECTIVES: Spectrum of post-traumatic symptoms is frequent among
      mild traumatic brain injury (mTBI) patients. They account for symptoms in 30-80
      per cent of patients during 3-4 months and 20-30 per cent of patients six months
      post-injury. There are no studies from India in this area. The present
      longitudinal study was conducted to evaluate the natural recovery of post
      traumatic symptoms in mTBI patients. METHODS: Twenty five mTBI patients
      presenting with initial Glasgow coma scale score of 15 were recruited initially 2
      3 wk post-injury. All patients were followed up twice, after 3-4 and 6-7 months.
      The patients were evaluated with neuropsychological test, post-traumatic symptoms
      and quality of life after injury. RESULTS: Sustained attention and sensory
      registration were first to improve. Memory and executive domains improved
      partially until three months and then after complete recovery. However, a few
      facets of learning/memory did not improve even at six months. The post-traumatic
      symptoms decreased since baseline from 76 to 52 per cent at 3-4 months and
      further to 28 per cent at 6-7 months. The quality of life improved partially from
      baseline till 3-4 months and much more by 6-7 months. INTERPRETATION &
      CONCLUSIONS: The study findings showed the course of changes in cognition,
      traumatic symptoms and quality of life since the time of injury till 6-7 months
      post-injury. Though majority of post-traumatic symptoms recovered after mTBI
      without any intervention, but residuals were not uncommon.

PMID- 29168464
TI  - Sustained progress, but no room for complacency: Results of 2015 HIV estimations
      in India.
AB  - BACKGROUND & OBJECTIVES: Evidence-based planning has been the cornerstone of
      India's response to HIV/AIDS. Here we describe the process, method and tools used
      for generating the 2015 HIV estimates and provide a summary of the main results.
      METHODS: Spectrum software supported by the UNAIDS was used to produce HIV
      estimates for India as a whole and its States/Union Territories. This tool takes
      into consideration the size and HIV prevalence of defined population groups and
      programme data to estimate HIV prevalence, incidence and mortality over time as
      well as treatment needs. RESULTS: India's national adult prevalence of HIV was
      0.26 per cent in 2015. Of the 2.1 million people living with HIV/AIDS, the
      largest numbers were in Andhra Pradesh, Maharashtra and Karnataka. New HIV
      infections were an estimated 86,000 in 2015, reflecting a decline by around 32
      per cent from 2007. The declining trend in incidence was mirrored in most States,
      though an increasing trend was detected in Assam, Chandigarh, Chhattisgarh,
      Gujarat, Sikkim, Tripura and Uttar Pradesh. AIDS-related deaths were estimated to
      be 67,600 in 2015, reflecting a 54 per cent decline from 2007. There were
      variations in the rate and trend of decline across India for this indicator also.
      INTERPRETATION & CONCLUSIONS: While key indicators measured through Spectrum
      modelling confirm success of the National AIDS Control Programme, there is no
      room for complacency as rising incidence trends in some geographical areas and
      population pockets remain the cause of concern. Progress achieved so far in
      responding to HIV/AIDS needs to be sustained to end the HIV epidemic.

PMID- 29168465
TI  - Investigation of the risk factors for pulmonary tuberculosis: A case-control
      study among Saharia tribe in Gwalior district, Madhya Pradesh, India.
AB  - BACKGROUND & OBJECTIVES: Prevalence of pulmonary tuberculosis (PTB) is known to
      be high in the indigenous tribal community Saharia in Madhya Pradesh, India. The
      risk factors for PTB are not well known among them. This study was done to
      determine various risk factors associated with PTB in the indigenous community
      Saharia. METHODS: A prevalence survey was conducted among Saharias of Gwalior
      district of Madhya Pradesh. The population surveyed was 12,123 which was the
      source of cases and controls for the present study. All the bacillary-positive
      cases and controls in the ratio of 1:5 were included in the survey. Data were
      collected by the trained health workers from the patients and controls using a
      semi-structured pre-coded and pre-tested questionnaire which included data on
      risk factors including demographic factors, host-related factors and household
      factors. The individuals were also screened for diabetes mellitus and HIV.
      RESULTS: Malnutrition and history of asthma were associated with an increased
      risk of PTB. More than 56 per cent cases were attributed to malnutrition and 12
      per cent attributed to asthma. Low family income, alcohol consumption and smoking
      were the other contributors. The risk was higher in males as compared to females.
      INTERPRETATION & CONCLUSIONS: The study emphasized that the main contributors
      were social factors. Nutrition supplementation, especially in tuberculosis (TB)
      patients and integrated approach to improve their living conditions are needed to
      control TB in this community.

PMID- 29168466
TI  - New Delhi metallo-beta-lactamase - type carbapenemases producing Escherichia coli
      isolates from hospitalized patients: A pilot study.
AB  - BACKGROUND & OBJECTIVES: Resistances to carbapenem group of antimicrobials among
      Escherichia coli due to production of carbapenemases, especially the New Delhi
      metallo-beta-lactamase (NDM) types, pose serious challenges in the treatment of
      infections in healthcare settings. This study was undertaken to detect NDM
      producing E. coli isolates from hospitalized patients with urinary tract
      infection (UTI). METHODS: A total of 30 non-repetitive isolates of E. coli from
      hospitalized patients with clinical suspicion of UTI were subjected to
      antimicrobial susceptibility testing. Screening for the production of extended
      spectrum beta-lactamases (ESBL) was carried out by minimum inhibitory
      concentration (MIC) test strip ESBL followed by phenotypic confirmation by double
      disc synergy test. Phenotypic confirmation of carbapenemase production was
      carried out by MIC test strip metallo-beta-lactamases. Molecular identification
      of the blaNDM gene was carried out by polymerase chain reaction (PCR) and
      sequencing of the amplified fragment. RESULTS: Seventeen of the 30 isolates were
      detected as ESBL producers, of which three were found to be carbapenemase
      producers. NDM genes were detected by PCR followed by gene sequencing in all
      three isolates positive for ESBL as well as carbapenemase. The amino acid
      sequence of the three isolates showed complete identity to the reference
      sequences of NDM-1, NDM-4 and NDM-8, respectively. INTERPRETATION & CONCLUSIONS:
      Our study showed the circulation of NDM variants among the clinical isolates of
      E. coli that were producers of ESBL as well as carbapenemase.

PMID- 29168467
TI  - Temporal trends of intestinal parasites in patients attending a tertiary care
      hospital in south India: A seven-year retrospective analysis.
AB  - BACKGROUND & OBJECTIVES: Intestinal parasitic infections and their associated
      complications are a major cause of morbidity in the developing world. This
      retrospective study was done to assess the prevalence of intestinal parasitic
      infections among patients in a tertiary healthcare setting and to analyze age-,
      gender- and time-related trends in the prevalence of these intestinal parasites
      over a seven year period (2006-2012). METHODS: The presence of various intestinal
      parasites in a tertiary care setting over a seven year period in different age
      groups was determined by performing routine stool microscopy. Modified acid-fast
      staining was performed for stool samples collected from children less than five
      years of age for the detection of intestinal coccidian parasites. Statistical
      analysis was carried out to analyze age-related trends in relation to the
      prevalence of commonly detected intestinal parasites. Seasonal fluctuations in
      parasite prevalence were evaluated by performing harmonic regression analysis.
      RESULTS: A total of 257,588 stool samples were received over the seven year
      period for examination. The highest percentage of intestinal parasites was in the
      6-10 yr age group. Among the intestinal parasites, Giardia intestinalis had the
      highest prevalence across most age groups, except in those above 60 yr of age
      where hookworm became more prevalent. A significant decreasing trend with age was
      observed for G. intestinalis, whereas for hookworm and Strongyloides stercoralis,
      an increasing trend with age was seen. Significant linear temporal trends were
      observed for parasites such as G. intestinalis, Entamoeba histolytica and Ascaris
      lumbricoides. INTERPRETATION & CONCLUSIONS: While G. intestinalis was more common
      in the younger age groups, certain soil-transmitted helminths such as hookworm
      and S. stercoralis showed a higher prevalence in the older populations.
      Significant temporal trends and seasonality were observed for some of the common
      intestinal parasites.

PMID- 29168468
TI  - Strontium chloride hexahydrate as a candidate molecule for long-term treatment of
      allergic rhinitis.
AB  - BACKGROUND & OBJECTIVES: Neurogenic inflammation plays a role in the
      pathophysiology of allergic rhinitis (AR). Strontium salts are highly effective
      in reducing the sensory irritation. This study was aimed to investigate the
      efficacy of strontium chloride (SC) on AR symptoms based on the duration of SC
      use before the symptoms begin. METHODS: Wistar albino rats (n=18) were randomly
      divided into three groups: Group 1, received 1MUg mometasone furoate (MF); Group
      2, three per cent SC; and Group 3 received five per cent SC (2 MUl/site). Drugs
      were administered to the each nasal cavity for three weeks every morning. On the
      days 7, 14 and 21, histamine dihydrochloride (HD) 5 MUmol (2 MUl/site) was
      administered and the frequencies of nasal rubbing and sneezing were counted for
      15 min. RESULTS: After 7, 14 and 21 day medication period, the groups were
      compared in terms of the frequency of sneezing and nasal rubbing following HD.
      There was a significant difference among the groups in terms of the frequency of
      sneezing on the day 7 (PPInterpretation & conclusions: Our results showed that
      three and five per cent SC were less effective than MF for sneezing during the
      first week, but the efficiency was equal to that of MF after the first 14 days.
      Long-term use of SC was as effective as MF on nasal rubbing. SC can be as
      effective as MF on both sneezing and nasal rubbing on regular use over three
      weeks.

PMID- 29168469
TI  - Bisphenol A-induced ultrastructural changes in the testes of common marmoset.
AB  - BACKGROUND & OBJECTIVES: Bisphenol A (BPA) is an endocrine disruptor that is
      widely used in the manufacture of polycarbonate plastics, epoxy resins and dental
      sealants. It is known to have adverse effects on spermatogenesis in rodents. This
      study was aimed to evaluate the effects of BPA in adult common marmoset owing to
      its similarities with human spermatogenesis. METHODS: Sixteen marmosets were
      divided into four groups (n=4 per group) and given oral doses of BPA (2.5, 12.5
      and 25 MUg/kg BW/day) for 70 days to cover two spermatogenic cycles, and the
      control group received only vehicle (honey). Testes were processed for
      histological and transmission electron microscopy studies. RESULTS: Histology of
      the testis showed sloughing of germ cells into the lumen, increase in
      interstitial space and vacuolation of Sertoli cell cytoplasm. Ultrastructural
      analysis of the testis revealed several degenerative effects on the basement
      membrane, Sertoli cells, Leydig cells and other developing germ cells in the 12.5
      and 25 MUg/kg BW/day groups as compared to control. INTERPRETATION & CONCLUSIONS:
      The observed ultrastructural changes caused by BPA in testicular morphology might
      be indicative of a perturbed sperm production. Considering the genetic and
      spermatogenic similarities of common marmoset (Callithrix jacchus) and humans,
      the study findings are of significance. Further studies are, however, needed to
      elucidate the mechanism of action.

PMID- 29168470
TI  - Seroepidemiology of parvovirus B19 among different age groups & pregnant women in
      India.

PMID- 29168471
TI  - Complete response of metastatic gastric cancer to chemoimmunotherapy.

PMID- 29168472
TI  - Characterization of naturally occurring pentacyclic triterpenes as novel
      inhibitors of deubiquitinating protease USP7 with anticancer activity in vitro.
AB  - Deubiquitinating protease USP7 is a promising therapeutic target for cancer
      treatment, and interest in developing USP7 inhibitors has greatly increased. In
      the present study, we reported a series of natural pentacyclic triterpenes with
      USP7 inhibitory activity in vitro. Among them, both the ursane triterpenes and
      oleanane triterpenes were more active than the lupine triterpenes, whereas
      ursolic acid was the most potent with IC50 of 7.0+/-1.5 MUmol/L. Molecular
      docking studies showed that ursolic acid might occupy the ubiquitin binding
      pocket of USP7, with the 17-carboxyl group and 3-hydroxyl group playing a vital
      role in the USP7-ursolic acid interaction. Using the cellular thermal shift
      assay, we demonstrated that ursolic acid interacted with USP7 in RPMI8226 human
      myeloma cells. Ursolic acid dose-dependently inhibited the proliferation of the
      myeloma cells with IC50 of 6.56 MUmol/L, accompanied by reductions in USP7
      substrates such as MDM2, UHRF1 and DNMT1. Overexpression of USP7 partially, but
      significantly attenuated ursolic acid-induced cell death as well as
      downregulation of MDM2, UHRF1 and DNMT1. In conclusion, we demonstrate for the
      first time that pentacyclic triterpenes represent a novel scaffold for developing
      USP7 inhibitors and that USP7 inhibition contributes to the anti-cancer effect of
      ursolic acid.

PMID- 29168473
TI  - Yangxin Tongmai Formula ameliorates impaired glucose tolerance in children with
      Graves' disease through upregulation of the insulin receptor levels.
AB  - Graves' disease (GD) is the leading cause of hyperthyroidism, and the majority of
      GD patients eventually develop disorders of glucose handling, which further
      affects their quality of life. Yangxin Tongmai formula (YTF) is modified from a
      famous formula of traditional Chinese medicine for the treatment of
      cardiovascular diseases. In this study we investigated the potential effects of
      YTF in the treatment of pediatric GD patients with impaired glucose tolerance.
      Forty pediatric GD patients and 20 healthy children were recruited for this
      clinical study. Based on the glucose tolerance, the GD patients were divided into
      two groups: 20 patients displayed impaired glucose tolerance, while the other 20
      patients displayed normal glucose tolerance. YTF was orally administered for 60
      days. YTF administration significantly ameliorated the abnormal glucose tolerance
      and insulin sensitivity in the GD patients with impaired glucose tolerance. To
      determine the molecular mechanisms of this observation, the number of plasma
      insulin receptors was determined by ELISA. Before treatment, the fasting and
      postprandial levels of the insulin receptor were significantly lower in patients
      with impaired glucose tolerance compared with those in patients with normal
      glucose tolerance and healthy children. After YTF treatment, both the fasting and
      the postprandial circulating insulin receptor levels were upregulated, and close
      to those in healthy children. Therefore, YTF is a potential effective treatment
      to enhance glucose handling in GD children with impaired glucose tolerance.

PMID- 29168475
TI  - Chronic kidney disease.
AB  - Chronic kidney disease (CKD) is defined by persistent urine abnormalities,
      structural abnormalities or impaired excretory renal function suggestive of a
      loss of functional nephrons. The majority of patients with CKD are at risk of
      accelerated cardiovascular disease and death. For those who progress to end-stage
      renal disease, the limited accessibility to renal replacement therapy is a
      problem in many parts of the world. Risk factors for the development and
      progression of CKD include low nephron number at birth, nephron loss due to
      increasing age and acute or chronic kidney injuries caused by toxic exposures or
      diseases (for example, obesity and type 2 diabetes mellitus). The management of
      patients with CKD is focused on early detection or prevention, treatment of the
      underlying cause (if possible) to curb progression and attention to secondary
      processes that contribute to ongoing nephron loss. Blood pressure control,
      inhibition of the renin-angiotensin system and disease-specific interventions are
      the cornerstones of therapy. CKD complications such as anaemia, metabolic
      acidosis and secondary hyperparathyroidism affect cardiovascular health and
      quality of life, and require diagnosis and treatment.

PMID- 29168476
TI  - Author Correction: A dynamic code for economic object valuation in prefrontal
      cortex neurons.
AB  - This corrects the article DOI: 10.1038/ncomms12554.

PMID- 29168477
TI  - Prevention: Saving lives: the importance of having Resolve.

PMID- 29168478
TI  - Supramolecular heterostructures formed by sequential epitaxial deposition of two
      dimensional hydrogen-bonded arrays.
AB  - Two-dimensional (2D) supramolecular arrays provide a route to the spatial control
      of the chemical functionality of a surface, but their deposition is in almost all
      cases limited to a monolayer termination. Here we investigated the sequential
      deposition of one 2D array on another to form a supramolecular heterostructure
      and realize the growth-normal to the underlying substrate-of distinct ordered
      layers, each of which is stabilized by in-plane hydrogen bonding. For
      heterostructures formed by depositing terephthalic acid or trimesic acid on
      cyanuric acid/melamine, we have determined, using atomic force microscopy under
      ambient conditions, a clear epitaxial arrangement despite the intrinsically
      distinct symmetries and/or lattice constants of each layer. Structures calculated
      using classical molecular dynamics are in excellent agreement with the
      orientation, registry and dimensions of the epitaxial layers. Calculations
      confirm that van der Waals interactions provide the dominant contribution to the
      adsorption energy and registry of the layers.

PMID- 29168479
TI  - Catalytic diastereo- and enantioselective additions of versatile allyl groups to
      N-H ketimines.
AB  - There are many biologically active organic molecules that contain one or more
      nitrogen-containing moieties, and broadly applicable and efficient catalytic
      transformations that deliver them diastereoselectively and/or enantioselectively
      are much sought after. Various methods for enantioselective synthesis of alpha
      secondary amines are available (for example, from additions to
      protected/activated aldimines), but those involving ketimines are much less
      common. There are no reported additions of carbon-based nucleophiles to
      unprotected/unactivated (or N-H) ketimines. Here, we report a catalytic,
      diastereo- and enantioselective three-component strategy for merging an N-H
      ketimine, a monosubstituted allene and B2(pin)2, affording products in up to 95%
      yield, >98% diastereoselectivity and >99:1 enantiomeric ratio. The utility of the
      approach is highlighted by synthesis of the tricyclic core of a class of
      compounds that have been shown to possess anti-Alzheimer activity. Stereochemical
      models developed with the aid of density functional theory calculations, which
      account for the observed trends and levels of enantioselectivity, are presented.

PMID- 29168480
TI  - Structural snapshots of concerted double E-H bond activation at a transition
      metal centre.
AB  - Bond activation at a transition metal centre is a key fundamental step in
      numerous chemical transformations. The oxidative addition of element-hydrogen
      bonds, for example, represents a critical step in a range of widely applied
      catalytic processes. Despite this, experimental studies defining steps along the
      bond activation pathway are very rare. In this work, we report on fundamental
      studies defining a new oxidative activation pathway: combined experimental and
      computational approaches yield structural snapshots of the simultaneous
      activation of both bonds of a beta-diketiminate-stabilized GaH2 unit at a single
      metal centre. Systematic variation of the supporting phosphine ligands and single
      crystal X-ray/neutron diffraction are exploited in tandem to allow structural
      visualization of the activation process, from a eta2-H,H sigma-complex showing
      little Ga-H bond activation, through species of intermediate geometry featuring
      stretched Ga-H and compressed M-H/M-Ga bonds, to a fully activated metal
      dihydride featuring a neutral (carbene-type) N-heterocyclic GaI ligand.

PMID- 29168481
TI  - Direct mapping of the angle-dependent barrier to reaction for Cl + CHD3 using
      polarized scattering data.
AB  - The transition state, which gates and modulates reactive flux, serves as the
      central concept in our understanding of activated reactions. The barrier height
      of the transition state can be estimated from the activation energy taken from
      thermal kinetics data or from the energetic threshold in the measured excitation
      function (the dependence of reaction cross-sections on initial collision
      energies). However, another critical and equally important property, the angle
      dependent barrier to reaction, has not yet been amenable to experimental
      determination until now. Here, using the benchmark reaction of Cl + CHD3(v1 = 1)
      as an example, we show how to map this anisotropic property of the transition
      state as a function of collision energy from the preferred reactant bond
      alignment of the backward-scattered products-the imprints of small impact
      parameter collisions. The deduced bend potential at the transition state agrees
      with ab initio calculations. We expect that the method should be applicable to
      many other direct reactions with a collinear barrier.

PMID- 29168482
TI  - UV-light-driven prebiotic synthesis of iron-sulfur clusters.
AB  - Iron-sulfur clusters are ancient cofactors that play a fundamental role in
      metabolism and may have impacted the prebiotic chemistry that led to life.
      However, it is unclear whether iron-sulfur clusters could have been synthesized
      on prebiotic Earth. Dissolved iron on early Earth was predominantly in the
      reduced ferrous state, but ferrous ions alone cannot form polynuclear iron-sulfur
      clusters. Similarly, free sulfide may not have been readily available. Here we
      show that UV light drives the synthesis of [2Fe-2S] and [4Fe-4S] clusters through
      the photooxidation of ferrous ions and the photolysis of organic thiols. Iron
      sulfur clusters coordinate to and are stabilized by a wide range of cysteine
      containing peptides and the assembly of iron-sulfur cluster-peptide complexes can
      take place within model protocells in a process that parallels extant pathways.
      Our experiments suggest that iron-sulfur clusters may have formed easily on early
      Earth, facilitating the emergence of an iron-sulfur-cluster-dependent metabolism.

PMID- 29168483
TI  - Bicyclic Baird-type aromaticity.
AB  - Classic formulations of aromaticity have long been associated with topologically
      planar conjugated macrocyclic systems. The theoretical possibility of so-called
      bicycloaromaticity was noted early on. However, it has yet to be demonstrated by
      experiment in a simple synthetic organic molecule. Conjugated organic systems are
      attractive for studying the effect of structure on electronic features. This is
      because, in principle, they can be modified readily through dedicated synthesis.
      As such, they can provide useful frameworks for testing by experiment with
      fundamental insights provided by theory. Here we detail the synthesis and
      characterization of two purely organic non-planar dithienothiophene-bridged
      [34]octaphyrins that permit access to two different aromatic forms as a function
      of the oxidation state. In their neutral forms, these congeneric systems contain
      competing 26 and 34 pi-electronic circuits. When subject to two-electron
      oxidation, electronically mixed [4n+1]/[4n+1] triplet biradical species in the
      ground state are obtained that display global aromaticity in accord with Baird's
      rule.

PMID- 29168485
TI  - Catalyst-controlled oligomerization for the collective synthesis of
      polypyrroloindoline natural products.
AB  - In nature, many organisms generate large families of natural product metabolites
      that have related molecular structures as a means to increase functional
      diversity and gain an evolutionary advantage against competing systems within the
      same environment. One pathway commonly employed by living systems to generate
      these large classes of structurally related families is oligomerization, wherein
      a series of enzymatically catalysed reactions is employed to generate secondary
      metabolites by iteratively appending monomers to a growing serial oligomer chain.
      The polypyrroloindolines are an interesting class of oligomeric natural products
      that consist of multiple cyclotryptamine subunits. Herein we describe an
      iterative application of asymmetric copper catalysis towards the synthesis of six
      distinct oligomeric polypyrroloindoline natural products: hodgkinsine,
      hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridine B and C. Given
      the customizable nature of the small-molecule catalysts employed, we demonstrate
      that this strategy is further amenable to the construction of quadrigemine H-type
      alkaloids not isolated previously from natural sources.

PMID- 29168486
TI  - Infrared spectrum and structure of the homochiral serine octamer-dichloride
      complex.
AB  - The amino acid serine is known to form a very stable octamer that has properties
      that set it apart from serine complexes of different sizes or from complexes
      composed of other amino acids. For example, both singly protonated serine
      octamers and anionic octamers complexed with two halogen ions strongly prefer
      homochirality, even when assembled from racemic D,L mixtures. Consequently, the
      structures of these complexes are of great interest, but no acceptable candidates
      have so far been identified. Here, we investigate anionic serine octamers
      coordinated with two chloride ions using a novel technique coupling ion mobility
      spectrometry-mass spectrometry with infrared spectroscopy, in combination with
      theoretical calculations. The results allow the identification of a unique
      structure for (Ser8Cl2)2- that is highly symmetric, very stable and homochiral
      and whose calculated properties match those observed in experiments.

PMID- 29168484
TI  - Global profiling of lysine reactivity and ligandability in the human proteome.
AB  - Nucleophilic amino acids make important contributions to protein function,
      including performing key roles in catalysis and serving as sites for post
      translational modification. Electrophilic groups that target amino-acid
      nucleophiles have been used to create covalent ligands and drugs, but have, so
      far, been mainly limited to cysteine and serine. Here, we report a chemical
      proteomic platform for the global and quantitative analysis of lysine residues in
      native biological systems. We have quantified, in total, more than 9,000 lysines
      in human cell proteomes and have identified several hundred residues with
      heightened reactivity that are enriched at protein functional sites and can
      frequently be targeted by electrophilic small molecules. We have also discovered
      lysine-reactive fragment electrophiles that inhibit enzymes by active site and
      allosteric mechanisms, as well as disrupt protein-protein interactions in
      transcriptional regulatory complexes, emphasizing the broad potential and diverse
      functional consequences of liganding lysine residues throughout the human
      proteome.

PMID- 29168487
TI  - Superatomic solids: Intercalation without altercation.

PMID- 29168488
TI  - Retraction: Oligoarginine peptides slow strand annealing and assist non-enzymatic
      RNA replication.
AB  - This corrects the article DOI: 10.1038/nchem.2551.

PMID- 29168489
TI  - Modular probes for enriching and detecting complex nucleic acid sequences.
AB  - Complex DNA sequences are difficult to detect and profile, but are important
      contributors to human health and disease. Existing hybridization probes lack the
      capability to selectively bind and enrich hypervariable, long or repetitive
      sequences. Here, we present a generalized strategy for constructing modular
      hybridization probes (M-Probes) that overcomes these challenges. We demonstrate
      that M-Probes can tolerate sequence variations of up to 7 nt at prescribed
      positions while maintaining single nucleotide sensitivity at other positions. M
      Probes are also shown to be capable of sequence-selectively binding a continuous
      DNA sequence of more than 500 nt. Furthermore, we show that M-Probes can detect
      genes with triplet repeats exceeding a programmed threshold. As a demonstration
      of this technology, we have developed a hybrid capture method to determine the
      exact triplet repeat expansion number in the Huntington's gene of genomic DNA
      using quantitative PCR.

PMID- 29168490
TI  - Single-crystal-to-single-crystal intercalation of a low-bandgap superatomic
      crystal.
AB  - The controlled introduction of impurities into the crystal lattice of solid-state
      compounds is a cornerstone of materials science. Intercalation, the insertion of
      guest atoms, ions or molecules between the atomic layers of a host structure, can
      produce novel electronic, magnetic and optical properties in many materials. Here
      we describe an intercalation compound in which the host [Co6Te8(PnPr3)6][C60]3,
      formed from the binary assembly of atomically precise molecular clusters, is a
      superatomic analogue of traditional layered atomic compounds. We find that
      tetracyanoethylene (TCNE) can be inserted into the superstructure through a
      single-crystal-to-single-crystal transformation. Using electronic absorption
      spectroscopy, electrical transport measurements and electronic structure
      calculations, we demonstrate that the intercalation is driven by the exchange of
      charge between the host [Co6Te8(PnPr3)6][C60]3 and the intercalant TCNE. These
      results show that intercalation is a powerful approach to manipulate the material
      properties of superatomic crystals.

PMID- 29168492
TI  - Thoroughly enthralling thulium.

PMID- 29168491
TI  - Structure and reactivity of a mononuclear gold(II) complex.
AB  - Mononuclear gold(II) complexes are very rare labile species. Transient gold(II)
      species have been suggested in homogeneous catalysis and in medical applications,
      but their geometric and electronic structures have remained essentially
      unexplored: even fundamental data, such as the ionic radius of gold(II), are
      unknown. Now, an unprecedentedly stable neutral gold(II) complex of a porphyrin
      derivative has been isolated, and its structural and spectroscopic features
      determined. The gold atom adopts a 2+2 coordination mode in between those of
      gold(III) (four-coordinate square planar) and gold(I) (two-coordinate linear),
      owing to a second-order Jahn-Teller distortion enabled by the relativistically
      lowered 6s orbital of gold. The reactivity of this gold(II) complex towards
      dioxygen, nitrosobenzene and acids is discussed. This study provides insight on
      the ionic radius of gold(II), and allows it to be placed within the homologous
      series of nd9 Cu/Ag/Au divalent ions and the 5d8/9/10 Pt/Au/Hg 'relativistic'
      triad in the periodic table.

PMID- 29168493
TI  - Site-selective oxidation, amination and epimerization reactions of complex
      polyols enabled by transfer hydrogenation.
AB  - Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a
      large set of natural and synthetic compounds, often with potent biological
      activity. In synthetic chemistry, alcohols are important precursors to carbonyl
      groups, which then can be converted into a wide range of oxygen- or nitrogen
      based functionality. Therefore, the selective conversion of a single hydroxyl
      group in natural products into a ketone would enable the selective introduction
      of unnatural functionality. However, the methods known to convert a simple
      alcohol, or even an alcohol in a molecule that contains multiple protected
      functional groups, are not suitable for selective reactions of complex polyol
      structures. We present a new ruthenium catalyst with a unique efficacy for the
      selective oxidation of a single hydroxyl group among many in unprotected polyol
      natural products. This oxidation enables the introduction of nitrogen-based
      functional groups into such structures that lack nitrogen atoms and enables a
      selective alcohol epimerization by stepwise or reversible oxidation and
      reduction.

PMID- 29168494
TI  - Vibronically coherent ultrafast triplet-pair formation and subsequent thermally
      activated dissociation control efficient endothermic singlet fission.
AB  - Singlet exciton fission (SF), the conversion of one spin-singlet exciton (S1)
      into two spin-triplet excitons (T1), could provide a means to overcome the
      Shockley-Queisser limit in photovoltaics. SF as measured by the decay of S1 has
      been shown to occur efficiently and independently of temperature, even when the
      energy of S1 is as much as 200 meV less than that of 2T1. Here we study films of
      triisopropylsilyltetracene using transient optical spectroscopy and show that the
      triplet pair state (TT), which has been proposed to mediate singlet fission,
      forms on ultrafast timescales (in 300 fs) and that its formation is mediated by
      the strong coupling of electronic and vibrational degrees of freedom. This is
      followed by a slower loss of singlet character as the excitation evolves to
      become only TT. We observe the TT to be thermally dissociated on 10-100 ns
      timescales to form free triplets. This provides a model for 'temperature
      independent' efficient TT formation and thermally activated TT separation.

PMID- 29168495
TI  - A unifying paradigm for naphthoquinone-based meroterpenoid (bio)synthesis.
AB  - Bacterial meroterpenoids constitute an important class of natural products with
      diverse biological properties and therapeutic potential. The biosynthetic logic
      for their production is unknown and defies explanation via classical biochemical
      paradigms. A large subgroup of naphthoquinone-based meroterpenoids exhibits a
      substitution pattern of the polyketide-derived aromatic core that seemingly
      contradicts the established reactivity pattern of polyketide phenol nucleophiles
      and terpene diphosphate electrophiles. We report the discovery of a hitherto
      unprecedented enzyme-promoted alpha-hydroxyketone rearrangement catalysed by
      vanadium-dependent haloperoxidases to account for these discrepancies in the
      merochlorin and napyradiomycin class of meroterpenoid antibiotics, and we
      demonstrate that the alpha-hydroxyketone rearrangement is potentially a conserved
      biosynthetic reaction in this molecular class. The biosynthetic alpha
      hydroxyketone rearrangement was applied in a concise total synthesis of
      naphthomevalin, a prominent member of the napyradiomycin meroterpenes, and sheds
      further light on the mechanism of this unifying enzymatic transformation.

PMID- 29168497
TI  - Molecular organic networks: A step beyond flatland.

PMID- 29168496
TI  - De novo design of a hyperstable non-natural protein-ligand complex with sub-A
      accuracy.
AB  - Protein catalysis requires the atomic-level orchestration of side chains,
      substrates and cofactors, and yet the ability to design a small-molecule-binding
      protein entirely from first principles with a precisely predetermined structure
      has not been demonstrated. Here we report the design of a novel protein, PS1,
      that binds a highly electron-deficient non-natural porphyrin at temperatures up
      to 100  degrees C. The high-resolution structure of holo-PS1 is in sub-A
      agreement with the design. The structure of apo-PS1 retains the remote core
      packing of the holoprotein, with a flexible binding region that is predisposed to
      ligand binding with the desired geometry. Our results illustrate the unification
      of core packing and binding-site definition as a central principle of ligand
      binding protein design.

PMID- 29168498
TI  - Enantioselective cyclizations and cyclization cascades of samarium ketyl
      radicals.
AB  - The rapid generation of molecular complexity from simple starting materials is a
      key challenge in synthesis. Enantioselective radical cyclization cascades have
      the potential to deliver complex, densely packed, polycyclic architectures, with
      control of three-dimensional shape, in one step. Unfortunately, carrying out
      reactions with radicals in an enantiocontrolled fashion remains challenging due
      to their high reactivity. This is particularly the case for reactions of radicals
      generated using the classical reagent, SmI2. Here, we demonstrate that
      enantioselective SmI2-mediated radical cyclizations and cascades that exploit a
      simple, recyclable chiral ligand can convert symmetrical ketoesters to complex
      carbocyclic products bearing multiple stereocentres with high enantio- and
      diastereocontrol. A computational study has been used to probe the origin of the
      enantioselectivity. Our studies suggest that many processes that rely on SmI2 can
      be rendered enantioselective by the design of suitable ligands.

PMID- 29168499
TI  - Polymer mechanochemistry: Up another rung.

PMID- 29168501
TI  - Erratum: Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity.
AB  - This corrects the article DOI: 10.1038/nature24302.

PMID- 29168500
TI  - A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ
      lineage.
AB  - Although individuals age and die with time, an animal species can continue
      indefinitely, because of its immortal germ-cell lineage. How the germline avoids
      transmitting damage from one generation to the next remains a fundamental
      question in biology. Here we identify a lysosomal switch that enhances germline
      proteostasis before fertilization. We find that Caenorhabditis elegans oocytes
      whose maturation is arrested by the absence of sperm exhibit hallmarks of
      proteostasis collapse, including protein aggregation. Remarkably, sperm-secreted
      hormones re-establish oocyte proteostasis once fertilization becomes imminent.
      Key to this restoration is activation of the vacuolar H+-ATPase (V-ATPase), a
      proton pump that acidifies lysosomes. Sperm stimulate V-ATPase activity in
      oocytes by signalling the degradation of GLD-1, a translational repressor that
      blocks V-ATPase synthesis. Activated lysosomes, in turn, promote a metabolic
      shift that mobilizes protein aggregates for degradation, and reset proteostasis
      by enveloping and clearing the aggregates. Lysosome acidification also occurs
      during Xenopus oocyte maturation; thus, a lysosomal switch that enhances oocyte
      proteostasis in anticipation of fertilization may be conserved in other species.

PMID- 29168502
TI  - A gut bacterial pathway metabolizes aromatic amino acids into nine circulating
      metabolites.
AB  - The human gut microbiota produces dozens of metabolites that accumulate in the
      bloodstream, where they can have systemic effects on the host. Although these
      small molecules commonly reach concentrations similar to those achieved by
      pharmaceutical agents, remarkably little is known about the microbial metabolic
      pathways that produce them. Here we use a combination of genetics and metabolic
      profiling to characterize a pathway from the gut symbiont Clostridium sporogenes
      that generates aromatic amino acid metabolites. Our results reveal that this
      pathway produces twelve compounds, nine of which are known to accumulate in host
      serum. All three aromatic amino acids (tryptophan, phenylalanine and tyrosine)
      serve as substrates for the pathway, and it involves branching and alternative
      reductases for specific intermediates. By genetically manipulating C. sporogenes,
      we modulate serum levels of these metabolites in gnotobiotic mice, and show that
      in turn this affects intestinal permeability and systemic immunity. This work has
      the potential to provide the basis of a systematic effort to engineer the
      molecular output of the gut bacterial community.

PMID- 29168505
TI  - Corrigendum: The 4D nucleome project.
AB  - This corrects the article DOI: 10.1038/nature23884.

PMID- 29168504
TI  - Mechanism of tandem duplication formation in BRCA1-mutant cells.
AB  - Small, approximately 10-kilobase microhomology-mediated tandem duplications are
      abundant in the genomes of BRCA1-linked but not BRCA2-linked breast cancer. Here
      we define the mechanism underlying this rearrangement signature. We show that, in
      primary mammalian cells, BRCA1, but not BRCA2, suppresses the formation of tandem
      duplications at a site-specific chromosomal replication fork barrier imposed by
      the binding of Tus proteins to an array of Ter sites. BRCA1 has no equivalent
      role at chromosomal double-stranded DNA breaks, indicating that tandem
      duplications form specifically at stalled forks. Tandem duplications in BRCA1
      mutant cells arise by a replication restart-bypass mechanism terminated by end
      joining or by microhomology-mediated template switching, the latter forming
      complex tandem duplication breakpoints. Solitary DNA ends form directly at Tus
      Ter, implicating misrepair of these lesions in tandem duplication formation.
      Furthermore, BRCA1 inactivation is strongly associated with ~10 kilobase tandem
      duplications in ovarian cancer. This tandem duplicator phenotype may be a general
      signature of BRCA1-deficient cancer.

PMID- 29168506
TI  - NFS1 undergoes positive selection in lung tumours and protects cells from
      ferroptosis.
AB  - Environmental nutrient levels impact cancer cell metabolism, resulting in context
      dependent gene essentiality. Here, using loss-of-function screening based on RNA
      interference, we show that environmental oxygen levels are a major driver of
      differential essentiality between in vitro model systems and in vivo tumours.
      Above the 3-8% oxygen concentration typical of most tissues, we find that cancer
      cells depend on high levels of the iron-sulfur cluster biosynthetic enzyme NFS1.
      Mammary or subcutaneous tumours grow despite suppression of NFS1, whereas
      metastatic or primary lung tumours do not. Consistent with a role in surviving
      the high oxygen environment of incipient lung tumours, NFS1 lies in a region of
      genomic amplification present in lung adenocarcinoma and is most highly expressed
      in well-differentiated adenocarcinomas. NFS1 activity is particularly important
      for maintaining the iron-sulfur co-factors present in multiple cell-essential
      proteins upon exposure to oxygen compared to other forms of oxidative damage.
      Furthermore, insufficient iron-sulfur cluster maintenance robustly activates the
      iron-starvation response and, in combination with inhibition of glutathione
      biosynthesis, triggers ferroptosis, a non-apoptotic form of cell death.
      Suppression of NFS1 cooperates with inhibition of cysteine transport to trigger
      ferroptosis in vitro and slow tumour growth. Therefore, lung adenocarcinomas
      select for expression of a pathway that confers resistance to high oxygen tension
      and protects cells from undergoing ferroptosis in response to oxidative damage.

PMID- 29168507
TI  - Orthogonal muscle fibres have different instructive roles in planarian
      regeneration.
AB  - The ability to regenerate missing body parts exists throughout the animal
      kingdom. Positional information is crucial for regeneration, but how it is
      harboured and used by differentiated tissues is poorly understood. In planarians,
      positional information has been identified from study of phenotypes caused by RNA
      interference in which the wrong tissues are regenerated. For example, inhibition
      of the Wnt signalling pathway leads to regeneration of heads in place of tails.
      Characterization of these phenotypes has led to the identification of position
      control genes (PCGs)-genes that are expressed in a constitutive and regional
      manner and are associated with patterning. Most PCGs are expressed within
      planarian muscle; however, how muscle is specified and how different muscle
      subsets affect regeneration is unknown. Here we show that different muscle fibres
      have distinct regulatory roles during regeneration in the planarian Schmidtea
      mediterranea. myoD is required for formation of a specific muscle cell subset:
      the longitudinal fibres, oriented along the anterior-posterior axis. Loss of
      longitudinal fibres led to complete regeneration failure because of defects in
      regeneration initiation. A different transcription factor-encoding gene, nkx1-1,
      is required for the formation of circular fibres, oriented along the medial
      lateral axis. Loss of circular fibres led to a bifurcated anterior-posterior axis
      with fused heads forming in single anterior blastemas. Whereas muscle is often
      viewed as a strictly contractile tissue, these findings reveal that different
      muscle types have distinct and specific regulatory roles in wound signalling and
      patterning to enable regeneration.

PMID- 29168509
TI  - Erratum: Early members of 'living fossil' lineage imply later origin of modern
      ray-finned fishes.
AB  - This corrects the article DOI: 10.1038/nature23654.

PMID- 29168510
TI  - A laboratory heterodyne emission spectrometer at submillimeter wavelengths.
AB  - We present first results on a newly built broadband emission spectrometer for the
      laboratory making use of a double sideband (DSB) heterodyne receiver. The new
      spectrometer is perfectly suited for high-resolution emission spectroscopy of
      molecules of astrophysical importance. The current SIS receiver operates at RF
      frequencies between 270 and 390 GHz, coincident with Band 7 of the ALMA
      telescope. The instantaneous bandwidth is 5 GHz (DSB). In this work the full
      spectrometer and its components are described. Its performance, in particular its
      sensitivity, stability, reproducibility and systematic errors, is characterized
      in detail. For this purpose very broad band emission spectra of methyl cyanide
      have been recorded and compared to theoretical spectra. Isotopic variants are
      found in natural abundance and features attributed to vibrationally excited
      species are all recorded in the same spectrum. The performance of the new
      spectrometer is compared extensively to that of a traditional FM-absorption
      spectrometer and to recent versions of chirped-pulse spectrometers operated in
      the mm-wave regime. Further applications and future advancements of the current
      instrument are discussed.

PMID- 29168508
TI  - Structural basis for the initiation of eukaryotic transcription-coupled DNA
      repair.
AB  - Eukaryotic transcription-coupled repair (TCR) is an important and well-conserved
      sub-pathway of nucleotide excision repair that preferentially removes DNA lesions
      from the template strand that block translocation of RNA polymerase II (Pol II).
      Cockayne syndrome group B (CSB, also known as ERCC6) protein in humans (or its
      yeast orthologues, Rad26 in Saccharomyces cerevisiae and Rhp26 in
      Schizosaccharomyces pombe) is among the first proteins to be recruited to the
      lesion-arrested Pol II during the initiation of eukaryotic TCR. Mutations in CSB
      are associated with the autosomal-recessive neurological disorder Cockayne
      syndrome, which is characterized by progeriod features, growth failure and
      photosensitivity. The molecular mechanism of eukaryotic TCR initiation remains
      unclear, with several long-standing unanswered questions. How cells distinguish
      DNA lesion-arrested Pol II from other forms of arrested Pol II, the role of CSB
      in TCR initiation, and how CSB interacts with the arrested Pol II complex are all
      unknown. The lack of structures of CSB or the Pol II-CSB complex has hindered our
      ability to address these questions. Here we report the structure of the S.
      cerevisiae Pol II-Rad26 complex solved by cryo-electron microscopy. The structure
      reveals that Rad26 binds to the DNA upstream of Pol II, where it markedly alters
      its path. Our structural and functional data suggest that the conserved Swi2/Snf2
      family core ATPase domain promotes the forward movement of Pol II, and elucidate
      key roles for Rad26 in both TCR and transcription elongation.

PMID- 29168511
TI  - A short non-cytotoxic antimicrobial peptide designed from Abeta29-40 adopts a
      nanostructure and shows in vivo anti-endotoxin activity.
AB  - Abeta29-40 residues with tryptophan in place of the lone methionine residue and
      three arginine residues added to its C-terminus exhibited augmented antibacterial
      activities and protected mice against a lethal dose of LPS. The results show the
      conversion of a Abeta29-40 segment into a cell-selective antimicrobial/anti
      endotoxin peptide with nanostructure and cation-pi interaction.

PMID- 29168512
TI  - Separation of Am3+ and Eu3+ using hexa-n-octylnitrilo triacetamide (HONTA):
      complexation, extraction, luminescence, EXAFS and DFT studies.
AB  - This paper reports the solvent extraction of Am3+ and Eu3+ using
      N,N,N',N',N'',N''-hexa-n-octylnitrilotriacetamide (HONTA) as the extractant in n
      dodecane. The results are in variance with those reported previously with respect
      to the nature of the extracted species. The solvent extraction data were entirely
      different from those reported previously as the extracted species conformed to 1
      : 2 (M : L) species for both Am3+ and Eu3+ ions. The structure of the extracted
      complex was determined by EXAFS demonstrating the three amidic 'O' atoms of the
      HONTA complex with the Eu3+ ion. In the case of the Am3+ ion, the pivotal 'N'
      atom is suggested to bond to the metal ion, which may explain the significantly
      more favourable extraction of Am3+vis-a-vis Eu3+. The absence of H2O molecules in
      the inner coordination sphere of the Eu3+-HONTA extract was confirmed by
      luminescence spectroscopic measurements. Complexation studies in MeOH and EtOH
      indicated the formation of both 1 : 1 and 1 : 2 complexes with Nd3+ ions. The
      results are explained on the basis of DFT calculations using HMNTA, the
      corresponding hexamethyl analogue of HONTA.

PMID- 29168503
TI  - Measurement of the multi-TeV neutrino interaction cross-section with IceCube
      using Earth absorption.
AB  - Neutrinos interact only very weakly, so they are extremely penetrating. The
      theoretical neutrino-nucleon interaction cross-section, however, increases with
      increasing neutrino energy, and neutrinos with energies above 40
      teraelectronvolts (TeV) are expected to be absorbed as they pass through the
      Earth. Experimentally, the cross-section has been determined only at the
      relatively low energies (below 0.4 TeV) that are available at neutrino beams from
      accelerators. Here we report a measurement of neutrino absorption by the Earth
      using a sample of 10,784 energetic upward-going neutrino-induced muons. The flux
      of high-energy neutrinos transiting long paths through the Earth is attenuated
      compared to a reference sample that follows shorter trajectories. Using a fit to
      the two-dimensional distribution of muon energy and zenith angle, we determine
      the neutrino-nucleon interaction cross-section for neutrino energies 6.3-980 TeV,
      more than an order of magnitude higher than previous measurements. The measured
      cross-section is about 1.3 times the prediction of the standard model, consistent
      with the expectations for charged- and neutral-current interactions. We do not
      observe a large increase in the cross-section with neutrino energy, in contrast
      with the predictions of some theoretical models, including those invoking more
      compact spatial dimensions or the production of leptoquarks. This cross-section
      measurement can be used to set limits on the existence of some hypothesized
      beyond-standard-model particles, including leptoquarks.

PMID- 29168513
TI  - 1,3,2-Diazaborole-derived carbene complexes of boron.
AB  - Reaction of 2-bromo-1,3,2-diazaborole (1) with excess BBr3 induces 1,2-hydrogen
      migration, giving 1,3,2-diazaborole-derived carbene complexes of boron bromide
      (2). Compound 2 exists in a dynamic solution equilibrium with 1. The 1H NMR study
      shows that the equilibrium lies to the right side of the dissociation reaction of
      2. Parallel reaction of 1 with excess BI3 gives the corresponding 1,3,2
      diazaborole-derived carbene boron iodide complex (3). Notably, in contrast to 2,
      the dissociation reaction of 3 largely lies to the left side, favouring the
      formation of 3. The dynamic solution equilibrium behaviours of 2 and 3 are probed
      by both experimental and theoretical methods.

PMID- 29168514
TI  - Specific protein supplementation using soya, casein or whey differentially
      affects regional gut growth and luminal growth factor bioactivity in rats;
      implications for the treatment of gut injury and stimulating repair.
AB  - Modulation of regional growth within specific segments of the bowel may have
      clinical value for several gastrointestinal conditions. We therefore examined the
      effects of different dietary protein sources on regional gut growth and luminal
      growth factor bioactivity as potential therapies. Rats were fed for 14 days on
      isonitrogenous and isocaloric diets comprising elemental diet (ED) alone (which
      is known to cause gut atrophy), ED supplemented with casein or whey or a soya
      protein-rich feed. Effects on regional gut growth and intraluminal growth factor
      activity were then determined. Despite calorie intake being similar in all
      groups, soya rich feed caused 20% extra total body weight gain. Stomach weight
      was highest on soya and casein diets. Soya enhanced diet caused greatest increase
      in small intestinal weight and preserved luminal growth factor activity at levels
      sufficient to increase proliferation in vitro. Regional small intestinal
      proliferation was highest in proximal segment in ED fed animals whereas distal
      small intestine proliferation was greater in soya fed animals. Colonic weight and
      proliferation throughout the colon was higher in animals receiving soya or whey
      supplemented feeds. We conclude that specific protein supplementation with either
      soya, casein or whey may be beneficial to rest or increase growth in different
      regions of the bowel through mechanisms that include differentially affecting
      luminal growth factor bioactivity. These results have implications for targeting
      specific regions of the bowel for conditions such as Crohn's disease and
      chemotherapy.

PMID- 29168517
TI  - Crossed beam polyatomic reaction dynamics: recent advances and new insights.
AB  - Over the past ten years or so, great advances in our understanding of the
      dynamics of elementary (bimolecular) polyatomic reactions in the gas-phase have
      occurred. This has been made possible by critical improvements (a) in crossed
      molecular beam (CMB) instruments with rotating mass spectrometric detection and
      time-of-flight analysis, especially following the implementation of soft
      ionization (by tunable low energy electrons or vacuum-ultraviolet synchrotron
      radiation) for product detection with increased sensitivity and universal
      detection power, and (b) in REMPI-slice velocity map ion imaging (VMI) detection
      techniques in pulsed CMB experiments for obtaining product pair-correlated
      information through high-resolution measurements directly in the center of mass
      system. The improved universal CMB method is permitting us to identify all
      primary reaction products, characterize their formation dynamics, and determine
      the branching ratios (BRs) for multichannel non-adiabatic reactions, such as
      those of ground state oxygen atoms, O(3P), with unsaturated hydrocarbons
      (alkynes, alkenes, dienes). The improved slice VMI CMB technique is permitting us
      to explore at an unprecedented level of detail, through pair-correlated
      measurements, the reaction dynamics of a prototype polyatomic molecule such as
      CH4 (and isotopologues) in its ground state with a variety of important X
      radicals such as F, Cl, O, and OH. In this review, we highlight this recent
      progress in the field of CMB reaction dynamics, with an emphasis on the
      experimental side, but with the related theoretical work, at the level of state
      of-the-art calculations of both the underlying potential energy surfaces and the
      reaction dynamics, noted throughout. In particular, the focus is (a) on the
      effect of molecular complexity and structure on product distributions, branching
      ratios and role of intersystem crossing for the multichannel, addition
      elimination reactions of unsaturated hydrocarbons with O atoms, and (b) on the
      very detailed dynamics of the abstraction reactions of ground-state methane (and
      isotopologues) with atoms (F, Cl, O) and diatoms (OH), with inclusion of also
      rotational mode specificity in the vibrationally excited methane reactions.

PMID- 29168516
TI  - Computational screening of functional groups for capture of toxic industrial
      chemicals in porous materials.
AB  - A thermodynamic analysis using quantum chemical methods was carried out to
      identify optimal functional group candidates that can be included in metal
      organic frameworks and activated carbons for the selective capture of toxic
      industrial chemicals (TICs) in humid air. We calculated the binding energies of
      14 critical TICs plus water with a series of 10 functional groups attached to a
      naphthalene ring model. Using vibrational calculations, the free energies of
      adsorption were calculated in addition to the binding energies. Our results show
      that, in these systems, the binding energies and free energies follow similar
      trends. We identified copper(i) carboxylate as the optimal functional group
      (among those studied) for the selective binding of the majority of the TICs in
      humid air, and this functional group exhibits especially strong binding for
      sulfuric acid. Further thermodynamic analysis shows that the presence of water
      weakens the binding strength of sulfuric acid with the copper carboxylate group.
      Our calculations predict that functionalization of aromatic rings would be
      detrimental to selective capture of COCl2, CO2, and Cl2 under humid conditions.
      Finally, we found that forming an ionic complex, H3O+HSO4-, between H2SO4 and H2O
      via proton transfer is not favorable on copper carboxylate.

PMID- 29168515
TI  - Coordination mode-induced isomeric cyclometalated [Ir(tpy)(nbi)Cl](PF6)
      complexes: distinct luminescence, self-assembly and cellular imaging behaviors.
AB  - Two isomeric Ir(iii) complexes Ir-O and Ir-R arising from the different
      coordination mode of a naphthalene-containing ligand, show distinct luminescence,
      self-assembly ability and cellular imaging behaviors.

PMID- 29168520
TI  - Vertical charge transport through transition metal dichalcogenides - a
      quantitative analysis.
AB  - Based on the careful design of two-terminal devices from multi-layer transition
      metal dichalcogenides (TMDs) such as MoS2 and WSe2, truly vertical transport has
      been experimentally evaluated and theoretically analyzed. By exploring, the
      electric field and temperature dependence of in total 28 TMD devices of various
      thicknesses, a model that describes vertical transport as Fowler Nordheim
      mediated at high electric fields and thermal injection dominated at low fields
      has been developed. Our approach is similar to the description chosen to capture
      gate leakage current levels through amorphous materials such as SiO2. Employing
      our quantitative analysis, an effective vertical transport mass of m*/m0 (MoS2) ~
      0.18 and m*/m0 (WSe2) ~ 0.14 has been extracted for the first time and barriers
      at the metal contact-to-TMD interface of heights similar to those extracted for
      lateral transport in TMD transistors have been confirmed.

PMID- 29168521
TI  - Carbon vacancies in Ti2CT2 MXenes: defects or a new opportunity?
AB  - Carbon vacancies are commonly present in two-dimensional (2D) MXenes that hold
      promise in a variety of applications whereas their behavior remains unknown. Here
      we report on the influence of carbon vacancies on the structural stability,
      electronic properties and stiffness of MXenes by taking Ti2CT2 (T = O, F, and OH)
      as an example. According to the first-principles calculations, the formation
      energies of carbon vacancies in MXenes are lower than those in other typical 2D
      materials including graphene and MoS2, in combination with high migration
      energies. These two features mean that carbon-vacant MXenes are thermodynamically
      and dynamically stable as further evidenced by the absence of structural
      reconstruction both in the ground state and at ambient temperature.
      Interestingly, carbon vacancies that are usually considered as defects
      substantially offer a new opportunity on at least two aspects: enhanced
      electronic conduction and reduced stiffness corresponding to improved
      flexibility. The localized states in the vicinity of the Fermi level introduced
      by carbon vacancies account for the prominent metallic characteristics in carbon
      vacant Ti2CT2 MXenes.

PMID- 29168518
TI  - Nb and Ta benzotriazole or benzoxazole phenoxide complexes as catalysts for the
      ring-opening polymerization of glycidol to synthesize hyperbranched
      polyglycerols.
AB  - A series of novel mononuclear (1a-7a and 1b-6b) as well as tetranuclear (8a and
      9a) niobium (Nb) and tantalum (Ta) complexes of benzotriazole or benzoxazole
      phenoxide pro-ligands bearing different substituents at the ortho and para
      positions of the phenol rings were synthesized and characterized. The reaction of
      NbCl5 or TaCl5 with one equivalent of benzotriazole or benzoxazole phenoxide pro
      ligands (L1H-L6H) in dry toluene or chloroform produced the corresponding
      chloride (1a-6a and 1b-6b) and ethoxy (7a) mononuclear Nb and Ta complexes in
      high yields. Furthermore, from the mononuclear Nb complexes (1a or 4a), a new
      structural form of tetrameric niobium complexes (8a and 9a) was synthesized
      through a controlled hydrolysis reaction. The molecular structures of complexes
      1b, 4b, 7a, 8a and 9a were unambiguously confirmed by single crystal X-ray
      diffraction analyses. Furthermore, all these complexes (1a-9a and 1b-6b) were
      tested as catalysts for the ring-opening polymerisation (ROP) of glycidol to
      synthesize hyperbranched polyglycerols (HPG) by using 1,1,1
      tris(hydroxymethyl)propane (TMP) as an initiator. The degree of branching (DB)
      observed was 0.30-0.54, which is an indication of hyperbranched structures. In
      particular, for the niobium complex with electron-withdrawing substituents on the
      benzoxazole phenoxide pro-ligand (5a), we achieved superior behavior for the ROP
      of glycidol in terms of activity, control of molecular weight (Mn) and molecular
      weight distributions (MWDs) (92% of glycidol to HPG, Mn = 10.52 kg mol-1, MWDs
      <1.33, DB = 0.53 and Tg = -57  degrees C). A highly hydrophilic nature was
      observed for the synthesized HPG polymer by water contact angle measurement (20
      degrees  to 35 degrees ).

PMID- 29168522
TI  - Close to the diffraction limit in high resolution ATR FTIR mapping: demonstration
      on micrometric multi-layered art systems.
AB  - This paper is aimed at demonstrating the potentiality of high resolution
      Attenuated Total Reflection Fourier Transform Infrared micro-mapping (micro-ATR
      FTIR) to reconstruct the images of micrometric multi-layered systems. This method
      can be an effective analytical alternative when the layer thickness requires high
      lateral resolution, and fluorescence or thermal effects prevent the deployment of
      conventional analytical techniques such as micro-Raman spectroscopy. This study
      demonstrates the high micro-ATR-FTIR setup performances in terms of lateral
      resolution, spectral quality and chemical image contrast using a new laboratory
      instrument equipped with a single element detector. The method has been first
      validated on mock-ups and then successfully applied on cross-sectional samples
      from real artworks: Leonardo da Vinci's mural painting, characterised by a few
      micrometers thin sequence of organic and inorganic layers, and an outdoor marble
      statue, with a complex sequence of decay products on its surface. This study
      paves the way to a new investigation modality of micrometric systems, combining
      high lateral resolution with excellent spectral quality, essential in the field
      of Cultural Heritage as well as in the wider area of materials and forensic
      sciences.

PMID- 29168523
TI  - Electroconductive nanoscale topography for enhanced neuronal differentiation and
      electrophysiological maturation of human neural stem cells.
AB  - Biophysical cues, such as topography, and electrical cues can provide external
      stimulation for the promotion of stem cell neurogenesis. Here, we demonstrate an
      electroconductive surface nanotopography for enhancing neuronal differentiation
      and the functional maturation of human neural stem cells (hNSCs). The
      electroconductive nanopatterned substrates were prepared by depositing a thin
      layer of titanium (Ti) with nanograting topographies (150 to 300 nm groove/ridge,
      the thickness of the groove - 150 MUm) onto polymer surfaces. The Ti-coated
      nanopatterned substrate (TNS) induced cellular alignment along the groove pattern
      via contact guidance and promoted focal adhesion and cytoskeletal reorganization,
      which ultimately led to enhanced neuronal differentiation and maturation of hNSCs
      as indicated by significantly elevated neurite extension and the upregulated
      expression of the neuronal markers Tuj1 and NeuN compared with the Ti-coated flat
      substrate (TFS) and the nanopatterned substrate (NS) without Ti coating.
      Mechanosensitive cellular events, such as beta1-integrin binding/clustering and
      myosin-actin interaction, and the Rho-associated protein kinase (ROCK) and
      mitogen-activated protein kinase/extracellular signal regulated kinase (MEK-ERK)
      pathways, were found to be associated with enhanced focal adhesion and neuronal
      differentiation of hNSCs by the TNS. Among the neuronal subtypes, differentiation
      into dopaminergic and glutamatergic neurons was promoted on the TNS. Importantly,
      the TNS increased the induction rate of neuron-like cells exhibiting
      electrophysiological properties from hNSCs. Finally, the application of pulsed
      electrical stimulation to the TNS further enhanced neuronal differentiation of
      hNSCs due probably to calcium channel activation, indicating a combined effect of
      topographical and electrical cues on stem cell neurogenesis, which postulates the
      novelty of our current study. The present work suggests that an electroconductive
      nanopatterned substrate can serve as an effective culture platform for deriving
      highly mature, functional neuronal lineage cells from stem cells.

PMID- 29168524
TI  - Confined naked gold nanoparticles in ionic liquid films.
AB  - Surface-clean Au nanoparticles (NPs) confined in films of ionic liquids (ILs) can
      be easily fabricated by sputtering deposition. A silicon wafer coated with films
      of both hydrophobic (bis((trifluoromethyl)sulfonyl)amide, NTf2-) and hydrophilic
      (tetrafluoroborate, BF4-) imidazolium-based ILs forms an 'ionic carpet-like'
      structure that can be easily decorated with Au NPs of 5.1 and 6.5 nm mean
      diameter, respectively. The depth profile distribution of the Au NPs depends on
      the arrangement of the IL, which is controlled mainly by the anion volume. Higher
      concentrations of Au NPs are found closer to the IL surface for the system
      containing a larger anion (NTf2) whereas Au NPs are located deeper in the IL for
      the system containing a smaller anion (BF4). The Au NPs are well distributed over
      the IL/Si support and are strictly confined in a single layer of the IL. This
      method is among the most simple and versatile for the generation of liquid layers
      containing surface-clean, stable and confined Au NPs.

PMID- 29168525
TI  - MXene: a potential candidate for yarn supercapacitors.
AB  - The increasing developments in wearable electronics demand compatible power
      sources such as yarn supercapacitors (YSCs) that can effectively perform in a
      limited footprint. MXene nanosheets, which have been recently shown in the
      literature to possess ultra-high volumetric capacitance, were used in this study
      for the fabrication of YSCs in order to identify their potential merit and
      performance in YSCs. With the aid of a conductive binder (PEDOT-PSS), YSCs with
      high mass loading of MXene are demonstrated. These MXene-based YSCs exhibit
      excellent device performance and stability even under bending and twisting. This
      study demonstrates that MXene is a promising candidate for YSCs and its further
      development can lead to flexible power sources with sufficient performance for
      powering miniaturized and/or wearable electronics.

PMID- 29168526
TI  - How the toxicity of nanomaterials towards different species could be
      simultaneously evaluated: a novel multi-nano-read-across approach.
AB  - Application of predictive modeling approaches can solve the problem of missing
      data. Numerous studies have investigated the effects of missing values on
      qualitative or quantitative modeling, but only a few studies have discussed it
      for the case of applications in nanotechnology-related data. The present study is
      aimed at the development of a multi-nano-read-across modeling technique that
      helps in predicting the toxicity of different species such as bacteria, algae,
      protozoa, and mammalian cell lines. Herein, the experimental toxicity of 184
      metal and silica oxide (30 unique chemical types) nanoparticles from 15 datasets
      is analyzed. A hybrid quantitative multi-nano-read-across approach that combines
      interspecies correlation analysis and self-organizing map analysis is developed.
      In the first step, hidden patterns of toxicity among nanoparticles are identified
      using a combination of methods. Subsequently, the developed model based on
      categorization of the toxicity of the metal oxide nanoparticle outcomes is
      evaluated via the combination of supervised and unsupervised machine learning
      techniques to determine the underlying factors responsible for the toxicity.

PMID- 29168530
TI  - Palladium-catalyzed tandem reaction of 2-chloroquinoline-3-carbaldehydes and
      isocyanides.
AB  - A facile domino reaction of 2-chloroquinoline-3-carbaldehydes in one and two
      equivalents of isocyanide has been investigated. Three-component reactions of 2
      chloroquinoline-3-carbaldehydes, isocyanides and amines are also described. In
      this Pd-catalyzed reaction under controlled conditions, three novel types of
      quinoline derivatives were formed via amidation, lactamization or carbamate
      formation along with the formation of C-C, C-N, and C-O bonds in a one-pot
      procedure.

PMID- 29168532
TI  - Complete tetraglycosylation of a calix[4]arene by a chemo-enzymatic approach.
AB  - Polyglycosylated calixarenes are efficient and selective multivalent ligands for
      lectins. However, the chemical decoration of these macrocyclic scaffolds with
      saccharides of increasing complexity is hampered by the highly complex chemistry
      of carbohydrates. An alternative to the conventional approach is the enzymatic
      diversification of simple glycocluster-presented glycans. In this work, we
      present a highly efficient chemo-enzymatic approach to tetra-N-acetyl
      lactosaminylcalix[4]arene via glycan extension catalyzed by a human beta-1,4
      galactosyltransferase. This demonstrates that calixarenes can be exhaustively
      processed by enzymatic glycosyl transfer despite the heavy steric crowding,
      paving the way to the design and achievement of multivalent ligands based on
      these macrocyclic scaffolds having complex branched glycans.

PMID- 29168533
TI  - Unprecedented carbon sub-microspheres with a porous hierarchy for highly
      efficient oxygen electrochemistry.
AB  - Developing efficient and robust electrocatalysts for bifunctional oxygen
      electrocatalysis is crucial for renewable energy technology. Herein, nitrogen and
      phosphorus co-doped carbon sub-microspheres with fascinating mesostructures are
      rationally synthesized through an effective soft-templating strategy. The unique
      features of substantial doping, large surface areas and well-defined porosity
      endow the dual-doped carbons with high-density electroactive sites, considerable
      active surface areas and improved mass transfer, ensuring impressive activity and
      durability in catalyzing oxygen reduction and evolution reactions, even competing
      with the noble metal benchmarks, thus assuring their use as an air cathode in a
      rechargeable Zn-air battery with low charge-discharge overpotential and
      remarkable long-term stability.

PMID- 29168534
TI  - Zero-dimensional methylammonium iodo bismuthate solar cells and synergistic
      interactions with silicon nanocrystals.
AB  - Organometal trihalide perovskite solar cells have attracted monumental attention
      in recent years. Today's best devices, based on a three-dimensional perovskite
      structure of corner-sharing PbI6 octahedra, are unstable, toxic, and display
      hysteresis in current-voltage measurements. We present zero-dimensional organic
      inorganic hybrid solar cells based on methylammonium iodo bismuthate
      (CH3NH3)3(Bi2I9) (MABI) comprising a Bi2I9 bioctahedra and observe very low
      hysteresis for scan rates in the broad range of 150 mV s-1 to 1500 mV s-1 without
      any interfacial layer engineering. We confirm good stability for devices produced
      and stored in open air without humidity control. The MABI structure can also
      accommodate silicon nanocrystals, leading to an enhancement in the short-circuit
      current. Through the material MABI, we demonstrate a promising alternative to the
      organometal trihalide perovskite class and present a model material for future
      composite third-generation photovoltaics.

PMID- 29168535
TI  - Highly reliable and low-noise solid-state nanopores with an atomic layer
      deposited ZnO membrane on a quartz substrate.
AB  - We present a fabrication scheme for a solid-state ZnO nanopore membrane directly
      deposited on top of a quartz substrate by atomic layer deposition (ALD) and
      investigate the characteristics of DNA translocation through the nanopores. We
      chose a ZnO membrane owing to its high isoelectric point (~9.5) as well as its
      chemical and mechanical stability. Aside from the extremely low noise level
      exhibited by this device on a highly insulating and low dielectric quartz
      substrate, it also slows down the translocation speed of DNA by more than one
      order of magnitude as compared to that of a SiNx nanopore device. We propose that
      the electrostatic interaction between the positively charged ZnO nanopore wall,
      resulting from the high isoelectric point of ZnO, and the negatively charged
      phosphate backbone of DNA provides an additional frictional force that slows down
      the DNA translocation.

PMID- 29168537
TI  - Pd-Catalyzed regioselective intramolecular dehydrogenative C-5 cross coupling in
      an N-substituted pyrrole-azole system.
AB  - Functionalized polycyclic pyrrole-azole structures possessing fused six membered
      and seven membered rings were directly synthesized via ligand-enabled, Pd
      catalyzed, site selective, intramolecular cross couplings of N-substituted
      pyrrole-azoles. C5-H activation in the presence of a reactive C2-H remains a
      challenge that needs to be addressed and this was targeted to be resolved through
      the present approach by specifically generating the cyclized products with 83
      100% selectivity. The featured methodology provides a novel disconnection for the
      synthesis of pyrrole containing alkaloids and medicinal compounds.

PMID- 29168538
TI  - Anxiety disorders and stressful events in Takotsubo syndrome.
AB  - BACKGROUND: Anxiety disorders are more common in Takotsubo syndrome (TS) than in
      acute coronary syndrome patients. The aim of this study was to investigate
      whether pre-existing anxiety disorders predispose to TS triggered by exclusively
      emotional stressful events. METHODS: Triggering events were compared in 58 TS
      patients with and without pre-existing anxiety disorders; clinical,
      electrocardiographic and echocardiographic data were also collected. RESULTS:
      Thirty-one (53%) patients had a previous history of anxiety disorders. The
      exclusively emotional stressful event-rate was higher in TS patients with pre
      existing anxiety disorder (74% vs. 30%, p = 0.001), while TS caused by an
      undetermined trigger were significantly higher in patients without anxiety
      disorders (33% vs. 10%, p = 0.027). Moreover, in TS patients without a previous
      history of anxiety disorders, a trend of higher prevalence of physical events was
      found (16% vs. 37%, p = 0.07). CONCLUSIONS: In patients with pre-existing anxiety
      disorders, TS was predominantly triggered by exclusively emotional stressful
      events, thereby suggesting a possible relationship between anxiety and emotional
      cardiac frailty in TS patients.

PMID- 29168539
TI  - Severe degenerative aortic stenosis with preserved ejection fraction does not
      change adipokines serum levels.
AB  - BACKGROUND: The role of the adipokines in the pathogenesis of aortic stenosis
      (AS) is not well established. The aim was to evaluate the relationship between
      adipokines and clinical characteristics as well as echocardiographic indices and
      noninvasive markers of vascular remodeling in patients with severe AS with
      preserved ejection fraction (EF). METHODS: Sixty-five patients (F/M: 38/27; age:
      68.3 +/- 9.0 years; body mass index [BMI]: 29.6 +/- 4.3 kg/m2) with severe AS
      with preserved EF: 33 patients with paradoxical low-flow low-gradient AS (PLFLG
      AS) and 32 patients with normal flow high-gradient AS (NFHG AS) were
      prospectively enrolled into the study. Twenty-four subjects (F/M: 14/10; age:
      65.4 +/- 8.7 years; BMI: 29.6 +/- 4.3 kg/m2) who matched as to age, sex, BMI and
      coronary artery disease (CAD) constituted the control group (CG). Clinical data
      and markers of vascular remodeling were related to the serum adipokines. RESULTS:
      There were no differences in the adipokines concentrations in the AS/CG. Patients
      with AS and coexisting CAD were characterized by decreased serum adiponectin (9.9
      +/- 5.5 vs. 12.7 +/- 5.8 MUg/mL, p = 0.040) and leptin (8.3 +/- 7.8 vs. 21.6 +/-
      17.1 ng/mL, p < 0.001) levels compared to subjects without CAD. There were no
      differences in the serum adipokines concentrations between patients with PLFLG AS
      and NFHG AS. Systemic hypertension, diabetes, hyperlipidemia or markers of
      vascular remodeling did not discriminate adipokines concentrations. Multivariate
      regression analysis indicated that age (F = 3.02; p = 0.015) and E/E' index (F =
      0.87, p = 0.032) were independent predictors of the adiponectin level in the AS
      group. CONCLUSIONS: The presence of AS with preserved EF did not change the
      adipokine serum profile. Adipokines levels were modified by coexisting
      atherosclerosis but not the typical cardiovascular risk factors or the
      hemodynamic type of AS.

PMID- 29168540
TI  - Identification of a peripheral blood long non-coding RNA (Upperhand) as a
      potential diagnostic marker of coronary artery disease.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) have been confirmed to be involved in
      the pathologi-cal processes of multiple diseases. However, the characteristic
      expression of lncRNAs in peripheral blood of coronary artery disease (CAD)
      patients and whether some of these lncRNAs can be used as diagnostic biomarkers
      for CAD requires further investigation. METHODS: Six healthy and CAD individuals
      were selected for microarray analysis, and 5 differentially expressed lncRNAs
      were selected and confirmed in the second cohort consisting of 30 control
      individu-als and 30 CAD patients with different SYNTAX scores. Upperhand were
      verified in the third cohort consisting of 115 controls and 137 CAD patients.
      RESULTS: Thirty one lncRNAs were differentially expressed between the two groups,
      among whom, 25 were upregulated in the CAD group and 6 were downregulated. Four
      of the selected five lncRNAs were significantly upregulated in the CAD group, and
      Upperhand had the largest area under the curve (AUC). The diagnostic value of
      Upperhand was tested further, and it remained having a high diagnostic value.
      CONCLUSIONS: The expression level of Upperhand in peripheral blood of CAD
      patients is significantly higher than in control individuals, and is correlated
      with severity of CAD. Upperhand is a potential diagnostic biomarker of CAD, and
      when combined with TCONS_00029157, diagnostic value slightly increased.

PMID- 29168541
TI  - Evaluation of bioresorbable vascular scaffolds in acute coronary syndrome: A two
      center, one-year follow-up analysis.
AB  - BACKGROUND: Bioresorbable vascular scaffolds (BVS) have emerged as a new
      treatment option in cardiovascular medicine. Nonetheless, there is still limited
      data on the use of these novel devices in patients with acute coronary syndromes
      (ACS). The purpose of this study was to evaluate the feasibility and efficacy of
      BVS implantation in patients with ACS. METHODS: The present report is a
      prospective, two-center registry that involved 165 consecutive patients
      hospitalized with the diagnosis of ACS and treated with the Absorb BVS (Abbot
      Vascular, Santa Clara, USA). During 1-year, all patients were monitored for the
      following endpoints: death, myocardial infarction (MI), scaffold thrombosis (ST),
      target lesion revascularization (TLR), target vessel revascularization (TVR) and
      target vessel failure (TVF), defined as cardiac death, target vessel MI, and TVR.
      RESULTS: A total of 165 patients underwent 179 BVS implantations. 94 patients
      were diagnosed with unstable angina (UA; 57.6%), 45 with non-ST-segment elevation
      myocardial infarction (NSTEMI; 27.3%) and 26 with ST-segment elevation myocardial
      infarction (STEMI; 15.7%). Procedural success was achieved in all patients with
      thrombolysis in myocardial infarction flow 3. During a follow-up of 14.1 +/- 8.5
      months (median 12.4 months, IQR 8.7 [8.4 to 12.1] months) death occurred in 4
      (2.4%) patients, including 2 (1.3%) cardiac deaths. There was only 1 case of
      subacute ST (0.66%), without late ST. The incidence of MI, TLR, TVR and TVF were:
      2.65%, 2.65%, 7.95%, 9.3%, respectively. CONCLUSIONS: The present results suggest
      that BVS implantation in ACS patients is feasible and safe in highly experienced
      centers. One-year clinical results are encouraging with a low rate of stent
      thrombosis.

PMID- 29168542
TI  - State-of-the-art of transcatheter treatment of aortic valve stenosis and the
      overview of the InFlow project aiming at developing the first Polish TAVI system.
AB  - Initial experience of transcatheter aortic valve implantation (TAVI) or
      replacement (TAVR) has ap-peared as a promising minimally invasive technology for
      patients disqualified from surgical treatment (SAVR). Safety and efficacy of TAVI
      has been analyzed and assessed through numerous registries and trials.
      Furthermore, results obtained from comparative TAVI vs. SAVR trials proved that
      both treat!ments can be considered equal in terms of post-procedural mortality
      and morbidity in high-risk, as well as lower risk patients. However, there are
      still some issues that have to be addressed, such as higher chance of
      paravalvular leakage, vascular injuries, conduction disturbances, malpositioning
      and the yet unmet problem of insufficient biological valves durability. Recent
      technological developments along with the learning curve of operators prove a
      great potential for improvement of TAVI and a chance of surpassing SAVR in
      various groups of patients in the near future. In pursuit of finding new
      solutions, the CardValve Consortium consisting of leading scientific and research
      institutions in Poland has been created. Under the name of InFlow and financial
      support from the National Center for Research and Development, they have started
      a project with the aim to design, create and implement into clinical practice the
      first, Polish, low-profile TAVI valve system, utilizing not only biological but
      also artificial, polymeric-based prosthesis. This review focuses on current
      developments in TAVI technologies including the InFlow project.

PMID- 29168543
TI  - Lipid-lowering therapy with PCSK9-inhibitors in the management of cardiovascular
      high-risk patients: Effectiveness, therapy adherence and safety in a real world
      cohort.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitors have
      shown great po-tential in efficient lipid lowering to achieve low-density
      lipoprotein-cholesterol (LDL-C) treatment goals. The aim of the study was too
      describe the clinical use of PCSK9-inhibitors and to investigate therapy
      adherence and safety outside of clinical trials. METHODS: Thirty-eight patients
      were treated with PSCK9-inhibitors. Patients were eligible for this therapy based
      on their individual cardiovascular risk and when all other available lipid
      lowering regi-men had failed. Every patient answered a questionnaire concerning
      medical history and relevant side effects and therapy adherence. RESULTS:
      Conventional therapy reduced patient LDL-C levels by about 38%. However, in 26 of
      the 38 patients, LDL-C treatment goals were not fulfilled because patients did
      not tolerate further dose es-calation due to side effects. Using a PCSK9
      inhibitor, LDL-C levels were reduced by another 54% and 42% of patients reaching
      treatment goals. The results show that most patients still require concomitant
      therapy to reach LDL-C target levels. Three patients required dose reduction or
      change of the PCSK9 inhibitor. 16% did not inject the PCSK9 inhibitor regularly.
      CONCLUSIONS: Only a minority of patients reached the recommended LDL-C goals.
      PCSK9-inhibitors were generally well tolerated. Despite low rates of reported
      side effects, therapy adherence was incom-plete, with 6 patients not injecting
      PCSK9-inhibitors on a regular basis. In-depth information about the medication
      and close supervision is advisable. PCSK9 inhibitors have shown great potential
      in aggressive lipid lowering therapy, but basic therapy is still required in most
      cases. Close supervision is recommended to improve therapy adherence. (Cardiol J
      2018; 25, 1: 32-41).

PMID- 29168544
TI  - Zalecenia postepowania diagnostycznego i leczniczego w osteoporozie w Polsce.
      Aktualizacja 2017.

PMID- 29168545
TI  - Letter to Readers.

PMID- 29168546
TI  - Glucocorticoids and beta-cell function.
AB  - Glucocorticoids (GCs) play a pivotal role in carbohydrate metabolism. They
      counteract insulin by decreasing peripheral glucose uptake and stimulating
      hepatic gluconeogenesis, although they are best known for inducing insulin
      resistance (IR). Moreover, GCs may attenuate the incretin effect. Nevertheless,
      their direct impact on beta cells is not fully defined. This review aims to
      present the current understanding of this subject. Humans exposed to GC excess
      display IR, impaired glucose tolerance, and eventually develop diabetes. Although
      their insulin levels are elevated, they present lower insulin output in response
      to glucose than obese individuals. Rodent models demonstrate that GC-induced IR
      is accompanied by compensatory beta-cell hyperplasia. GC excess with high-fat
      diet leads to fasting hyperglycaemia and suppressed glucose-stimulated insulin
      secretion (GSIS) despite increased beta cell mass. The majority of in vitro
      studies confirm an inhibitory GC effect on insulin secretion. The mechanism
      remains ambiguous but might involve its direct influence upon expression of
      molecules essential for glucose sensing and metabolism, enhanced glucose cycling,
      down-regulated insulin gene transcription, hampered insulin exocytosis, amplified
      alpha-adrenergic signalling, and/or increased beta-cell apoptosis. There are also
      reports that suggest increased GSIS after beta cell exposure to GCs in vitro.
      Transgenic mice with enhanced corticosterone regeneration within their beta cells
      present augmented secretory capacity of their islets. To summarise, GCs exert a
      significant role in carbohydrate balance through various mechanisms, including
      direct impact on beta cell function. Observed discrepancies may arise from
      differences in study design. A thorough understanding of GC action will provide
      important clinical clues for disorders of glucose homeostasis.

PMID- 29168547
TI  - Gastric Contractility Modulation - a novel method for the treatment of type 2
      diabetes mellitus and obesity.
AB  - Because the majority of antidiabetic medications are of limited efficacy and
      patient compliance with treatment is usually poor, new therapies are still being
      searched for. In the review a newly developed system for treatment of subjects
      with type 2 diabetes and concomitant overweight/obesity is described. The system
      consists of an implantable pulse generator that delivers electrical stimuli
      through leads implanted in the sero-muscular layer of the stomach. The device
      recognises and automatically modulates natural electrical activity of the stomach
      during meals, strengthening gastric contractility. This increase in the force of
      contractions enhances vagal afferent activity. Modulated signals are transmitted
      to the regulatory centres in the brain in order to provoke an early response of
      the gut typical of a full meal. Clinical trials performed to date show that the
      system improves glycaemic control with minimal patient compliance needed and with
      added benefits of body weight loss, a decrease in blood pressure, and favourable
      changes in the lipid profile. The system is safe, well-tolerated, with a low risk
      of hypoglycaemia, and will probably become an alternative to the use of incretins
      or to bariatric surgery in obese patients who are unwilling to undergo a major
      and anatomically irreversible operation.

PMID- 29168548
TI  - Guidelines for the diagnosis and management of osteoporosis in Poland : Update
      2017.
AB  - In the rapidly ageing society in Poland, osteoporosis is a growing
      epidemiological problem, and osteoporosis-related fractures are a cause of
      chronic disability and considerable increase of death risk. It turns out that 80
      to 90% of patients suffering from osteoporosis, including osteoporosis
      accompanied by fractures, do not receive adequate pharmacotherapy. In this paper,
      a Guideline Working Group of experts from the Multidisciplinary Osteoporosis
      Forum update the existing Polish guidelines concerning the diagnosis and
      management of osteoporosis (last revised in 2013), taking account of the latest
      literature, availability and reimbursement of drugs, and current health care
      organisation. In the revised guidelines, we still postulate that tasks are
      divided between primary care doctors (stage I) and specialists in osteoporosis
      management (stage II). We emphasise the necessity of early initiation of
      pharmacotherapy and rehabilitation in all patients with low-energy fractures. We
      recommend that the 10-year fracture risk should be estimated in all patients
      (including those without fractures) who are over 50 years of age, and that the
      Polish threshold for therapeutic intervention should be adopted: >= 10% for FRAX
      PL calculator. We add strategies of drug choice and therapy monitoring with
      imaging, and densitometric and biochemical diagnostics. We define basic
      guidelines concerning prevention of falls, rehabilitation, and dietary
      procedures, and elimination of environmental and other fracture risk factors. We
      point to two vital elements for improving osteoporosis management: 1) strategy of
      supervision over fractures management - Fracture Liaison Service (FLS), and,
      optimally, 2) strategies of short-term monitoring of the therapeutic efficacy
      with the use of biochemical markers.

PMID- 29168549
TI  - First Polish analysis of the treatment of advanced heart failure in children with
      the use of BerlinHeart EXCOR mechanical circulatory support.
AB  - BACKGROUND: The treatment of advanced heart failure (HF) in children and infants
      poses a serious management problem. Heart failure in that patient group is
      usually of congenital aetiology. The treatment schedules for paediatric patients
      are in most cases adapted from the guidelines for treatment of adults. Up to
      2009, the treatment of that extremely difficult group of patients was limited to
      pharmacological therapy and occasional heart transplantations. Constantly
      increasing problems with recruiting donors, especially for the paediatric group,
      contribute to the fact that mechanical support with the use of ventricular assist
      devices is for many children the only chance of surviving the period of waiting
      for a heart donor. AIM: The aim of the study was to analyse the outcomes of
      circulatory support in Poland and to assess the advisability of this method for
      treatment of children with severe HF. METHODS: This treatment of paediatric
      patients is currently used in three Polish centres. From December 28, 2009 to
      August 1, 2015, 27 implantations of BerlinHeart EXCOR(r) mechanical circulatory
      support system were performed in children aged from one month to 16 years (10
      patients below one year of age; 37%). Left ventricular assist devices were
      implanted to 21 patients, whereas the remaining children received biventricular
      support. The most common reason for using this method was HF developed in the
      course of cardiomyopathy. In one case, HF after Fontan operation was the
      indication. RESULTS: The duration of the circulatory support period ranged from
      six to 1215 days. It was followed by successful heart transplantations in 10
      (37%) patients, in five (18.1%) it resulted in regeneration of the heart,
      enabling explantation of the device, whereas three children are still waiting for
      transplantations. Nine (33%) children died during the therapy because of
      thromboembolic complications. CONCLUSIONS: As follows from our data, circulatory
      support utilising the BerlinHeart EXCOR(r) system is an effective and promising
      method used as a bridge to cardiac transplantation, or for regeneration of the
      myocardium in paediatric patients. In the group of the youngest and the most
      difficult patients, the method requires close cooperation of the medical and
      nursing personnel.

PMID- 29168550
TI  - Automated external defibrillator use in public places: a study of acquisition
      time.
AB  - BACKGROUND: Sudden cardiac arrest (SCA) is a frequent cause of death in the
      developed world. Early defibrillation, preferably within the first minutes of the
      incident, significantly increases survival rates. Accessible automated external
      defibrillators (AED) in public areas have been promoted for many years, and
      several locations are equipped with these devices. AIM: The aim of the study was
      to assess the real-life availability of AEDs and assess possible sources of
      delay. METHODS: The study took place in the academic towns of Poznan, Lodz, and
      Warsaw, Poland. The researchers who were not aware of the exact location of the
      AED in the selected public locations had to deliver AED therapy in simulated SCA
      scenarios. For the purpose of the trial, we assumed that the SCA takes place at
      the main entrance to the public areas equipped with an AED. RESULTS: From
      approximately 200 locations that have AEDs, 78 sites were analysed. In most
      places, the AED was located on the ground floor and the median distance from the
      site of SCA to the nearest AED point was 15 m (interquartile range [IQR] 7-24;
      range: 2-163 m). The total time required to deliver the device was 96 s (IQR 52
      144 s). The average time for discussion with the person responsible for the AED
      (security officer, staff, etc.) was 16 s (IQR 0-49). The AED was located in open
      access cabinets for unrestricted collection in 29 locations; in 10 cases an AED
      was delivered by the personnel, and in 29 cases AED utilisation required
      continuous personnel assistance. The mode of accessing the AED device was related
      to the longer discussion time (p < 0.001); however, this did not cause any
      significant delay in therapy (p = 0.132). The AED was clearly visible in 34
      (43.6%) sites. The visibility of AED did not influence the total time of
      simulated AED implementation. CONCLUSIONS: We conclude that the access to AED is
      relatively fast in public places. In the majority of assessed locations, it meets
      the recommended time to early defibrillation of under 3 min from the onset of the
      cardiac arrest; however, there are several causes for possible delays. The AED
      signs indicating the location of the device should be larger. AEDs should also be
      displayed in unrestricted areas for easy access rather than being kept under
      staff care or in cabinets.

PMID- 29168551
TI  - Clinical characteristics, and in-hospital and long-term outcomes of stable angina
      treatment in patients below and over 40 years of age (from the PRESAGE registry).
AB  - BACKGROUND: There is a paucity of data concerning young patients with stable
      angina (SA). AIM: The study aimed to compare the characteristics, as well as in
      hospital one-, two-, and five-year outcomes of patients aged <= 40 and > 40 years
      with SA. METHODS: The analysis involved 80 patients aged <= 40 years and 9299
      patients aged > 40 years with SA treated in the 3rd Department of Cardiology in
      Zabrze between 2006 and 2014, and enrolled in the ongoing PRESAGE Registry.
      Propensity scores matching was used to adjust for differences in patients'
      baseline characteristics. The composite endpoint involved death, non-fatal
      myocardial infarction, and acute coronary syndrome (ACS) or ACS-driven unplanned
      revascularisation within one-, two-, and five-year follow-up periods. RESULTS: In
      comparison to older patients, the younger ones had a higher incidence of smoking
      (58.3% vs. 35.2%, p < 0.0001) and previous percutaneous angioplasty (45% vs.
      33.7%, p = 0.033). There was no significant difference in in-hospital outcomes.
      The composite endpoint incidence did not differ significantly between the young
      and old group within one year (1.3% vs. 8.1%, p = 0.068), two years (5.8% vs.
      12.9%, p = 0.08), and five years (23.1% vs. 25.7%, p = 0.71) after discharge.
      Young patients had a borderline lower mortality rate (0% vs. 4.5%, p = 0.053)
      after a one-year follow-up and a significantly lower mortality rate within two
      and five years after index hospitalisation (0% vs. 7.8%, p = 0.02 and 5.1% vs.
      17.1%, p = 0.04, respectively). After propensity score matching analysis, a
      significantly lower two-year mortality was observed in the <= 40 age group (0%
      vs. 8.1%; p = 0.016), without significant difference during five-year follow-up
      (5.1% vs. 13.5%; p = 0.21). CONCLUSIONS: The younger and older groups of patients
      with SA differed in clinical characteristics, with no significant difference in
      the in-hospital outcomes and composite endpoint incidence in the follow-up
      period. However, younger patients had a borderline lower mortality rate one year
      after discharge and a significantly lower mortality rate two and five years after
      the index hospitalisation.

PMID- 29168552
TI  - Predictors of post-operative atrial fibrillation in patients undergoing isolated
      coronary artery bypass grafting.
AB  - BACKGROUND: Post-operative atrial fibrillation (POAF) is the most common cardiac
      arrhythmia occurring after coronary artery bypass grafting (CABG). Arrhythmia
      leads to prolonged hospitalisation and may have an impact on both short-term and
      long-term prognoses. AIM: The aim of this paper was to evaluate the incidence of
      POAF in patients after CABG as well as to identify its predictors. METHODS: The
      study was performed on 791 patients (selected from a group of 1031 patients who
      underwent CABG in the Clinical Department of Cardiology in the years 2009-2011)
      who did not suffer from atrial fibrillation (AF) prior to isolated CABG. Data on
      co-existing diseases, as well as data collected at the time of surgery and in the
      post-operative period, were evaluated. RESULTS: The average age of patients in
      the examined group was 64.6 +/- 9.1 years. Emergency CABG was performed on 38% of
      patients, whereas 75.1% of patients underwent CABG with the use of extracorporeal
      circulation. Based on the incidence of POAF, the post-CABG patients were
      classified into a POAF(+) group that comprised 166 (21%) patients, and a POAF(-)
      group involving 625 (79%) patients. The first occurrence of arrhythmia during the
      first three days after surgery was observed in 76.5% of patients. The average age
      of POAF(+) and POAF(-) patients was 68.7 +/- 8.8 years and 63.5 +/- 8.9 years,
      respectively (p < 0.0001). The respective incidence rates of co-existing diseases
      in patients with POAF and those without POAF were as follows: arterial
      hypertension, 80.1% vs. 75.8% (p = 0.29); heart failure, 18.7% vs. 21.1% (p =
      0.56); type 2 diabetes, 24.1% vs. 26.2% (p = 0.64). Stable angina pectoris was
      diagnosed in 22.3% of patients with POAF and 15% of patients without POAF (p =
      0.034). The following conditions were more frequently observed in patients with
      POAF compared with those without POAF: low cardiac output syndrome, 28.9% vs.
      14.2% (p < 0.0001) and cardiac tamponade, 9% vs. 4.6% (p = 0.044), respectively.
      Red blood cell transfusions were performed more often in patients with POAF
      compared to those without POAF (70.5% vs. 55.7%, respectively, p = 0.0008).
      Multivariate analysis revealed the following potential predictors of POAF: age >=
      70 years (HR 2.3), preoperative stable angina pectoris (HR 1.7), and post-CABG
      low cardiac output syndrome (HR 1.8). CONCLUSIONS: POAF was diagnosed in 21% of
      post-CABG patients, and the major predictors were: age >= 70 years, preoperative
      stable angina, as well as low cardiac output syndrome following CABG.

PMID- 29168553
TI  - Probing the activity of a recombinant Zn2+ -transporting P-type ATPase.
AB  - P-type ATPase proteins maintain cellular homeostasis and uphold critical
      concentration gradients by ATP-driven ion transport across biological membranes.
      Characterization of single-cycle dynamics by time-resolved X-ray scattering
      techniques in solution could resolve structural intermediates not amendable to
      for example crystallization or cryo-electron microscopy sample preparation. To
      pave way for such time-resolved experiments, we used biochemical activity
      measurements, Attenuated Total Reflectance (ATR) and time-dependent Fourier
      Transform Infra-Red (FTIR) spectroscopy to identify optimal conditions for
      activating a Zn2+ -transporting Type-I ATPase from Shigella sonnei (ssZntA) at
      high protein concentration using caged ATP. The highest total activity was
      observed at a protein concentration of 25 mg/mL, at 310 K, pH 7, and required the
      presence of 20% (v/v) glycerol as stabilizing agent. Neither the presence of
      caged ATP nor increasing lipid-to-protein ratio affected the hydrolysis activity
      significantly. This work also paves way for characterization of recombinant metal
      transporting (Type-I) ATPase mutants with medical relevance.

PMID- 29168554
TI  - Relation between denaturation time measured by optical coherence reflectometry
      and thermal lesion depth during radiofrequency cardiac ablation: Feasibility
      numerical study.
AB  - BACKGROUND/OBJECTIVE: Radiofrequency (RF) catheter ablation is a minimally
      invasive medical procedure used to thermally destroy the focus of cardiac
      arrhythmias. Novel optical techniques are now being integrated into RF catheters
      in order to detect the changes in tissue properties. Loss of birefringence due to
      fiber denaturation at around 70 degrees C is related to changes in accumulated
      phase retardation and can be measured by polarization-sensitive optical coherence
      reflectometry (PS-OCR). Since irreversible thermal lesions are produced when the
      tissue reaches 50 degrees C, our goal was to seek the mathematical relationship
      between both isotherms. MATERIALS AND METHODS: A two-dimensional model based on a
      coupled electric-thermal problem was built and solved using the finite element
      method. The model consisted of cardiac tissue, blood, and a non-irrigated
      electrode with a sensor embedded in its tip to maintain a specific target
      electrode temperature. Computer simulations were conducted by varying the tissue
      characteristics. Lesion depth was estimated by the 50 degrees C isotherm, while
      the denaturation time (TD) was taken as the time at which the 70 degrees C
      isotherm reached a depth of 0.75 mm (which corresponds to the optical depth
      reached by PS-OCR technology). RESULTS: A strong correlation (R2  > 0.83) was
      found between TD and lesion depth and an even stronger correlation (R2  > 0.96)
      was found between TD and the time required to achieve a specific lesion depth.
      For instance, the ablation time required to ensure a minimum lesion depth of 3 mm
      was 1.33 * TD + 3.93 * seconds. CONCLUSIONS: The computer results confirmed the
      strong relationship between denaturation time and lesion depth and suggest that
      measuring denaturation time by PS-OCR could provide information on the ablation
      time required to reach a specific lesion depth. Lasers Surg. Med. 50:222-229,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29168555
TI  - Skeletal open-bite treatment with zygomatic anchorage for a child with mental
      retardation: A new modality.
AB  - Anterior open bite (AOB) is one of the most difficult malocclusions to treat and
      maintain in orthodontics. Malocclusion occurs more frequently in children with
      disabilities than in healthy children. Surgical correction of severe AOB often
      requires maxillary impaction to reduce the anterior facial height. The zygomatic
      buttress area could be a valuable anchorage site to achieve intrusion of
      maxillary posterior teeth. A 16-year-old boy with mental retardation showing
      signs of persistence of infantile behavior, decreased cognitive functioning, and
      psychomotor skill deficits (no identified syndrome) with an AOB was treated by
      intrusion of maxillary posterior teeth using I-shaped multipurpose titanium
      miniplate (SK Surgicals, India). A 7 mm AOB was corrected after 6 months of
      intrusion. The benefits of this treatment as an alternative to conventional
      orthodontic appliances are significant in subjects who lack the understanding or
      with manual dexterity to use an orthopedic appliance.

PMID- 29168556
TI  - Preliminary results of a cohort study of induction chemotherapy-based treatment
      for locally recurrent rectal cancer.
AB  - BACKGROUND: A significant number of patients treated for locally recurrent rectal
      cancer have local or systemic failure, especially after incomplete surgical
      resection. Neoadjuvant treatment regimens in patients who have already undergone
      preoperative (chemo)radiotherapy for the primary tumour are limited. The
      objective of the present study was to evaluate the influence of a neoadjuvant
      regimen incorporating induction chemotherapy (ICT) in patients with locally
      recurrent rectal cancer who had preoperative (chemo)radiotherapy for the primary
      cancer or an earlier local recurrence. METHODS: Patients were treated with a
      sequential neoadjuvant regimen including three or four cycles of 5-fluorouracil
      and oxaliplatin-containing chemotherapy. When no progressive disease was found at
      evaluation, neoadjuvant treatment was continued with chemoradiation therapy
      (CRRT) using 30 Gy with concomitant capecitabine. If there was a response to ICT,
      the patient was advised to continue with systemic chemotherapy after CRRT as
      consolidation chemotherapy while waiting for resection. These patients were
      compared with patients who received CRRT alone in the same time interval.
      RESULTS: Of 58 patients who had ICT, 32 (55 per cent) had surgery with clear
      resection margins, of whom ten (17 per cent) exhibited a pathological complete
      response (pCR). The remaining 26 patients had 23 R1 and three R2 resections. In
      71 patients who received CRRT, a similar rate of R0 (35 patients) and R1 (36)
      resection was found (P = 0.506), but only three patients (4 per cent) had a pCR
      (P = 0.015). CONCLUSION: The incorporation of ICT in neoadjuvant regimens for
      locally recurrent rectal cancer is a promising strategy.

PMID- 29168557
TI  - Probiotics for vulvovaginal candidiasis in non-pregnant women.
AB  - BACKGROUND: Vulvovaginal candidiasis (VVC) is estimated to be the second most
      common form of infection after bacterial vaginosis. The ability of probiotics in
      maintaining and recovering the normal vaginal microbiota, and their potential
      ability to resist Candidas give rise to the concept of using probiotics for the
      treatment of VVC. OBJECTIVES: To assess the effectiveness and safety of
      probiotics for the treatment of vulvovaginal candidiasis in non-pregnant women.
      SEARCH METHODS: We searched the following databases to October 2017: Sexually
      Transmitted Infections Cochrane Review Group's Specialized Register, CENTRAL,
      MEDLINE, Embase and eight other databases. We searched in following international
      resources: World Health Organization International Clinical Trials Registry
      Platform, ClinicalTrials.gov, Web of Science and OpenGrey. We checked specialty
      journals, reference lists of published articles and conference proceedings. We
      collected information from pharmaceutical companies and experts in the field.
      SELECTION CRITERIA: Randomized controlled trials (RCT) using probiotics, alone or
      as adjuvants to conventional antifungal drugs, to treat VVC in non-pregnant
      women. Trials recruiting women with recurrent VVC, coinfection with other
      vulvovaginal infections, diabetes mellitus, immunosuppressive disorders or taking
      immunosuppressant medication were ineligible for inclusion. Probiotics were
      included if they were made from single or multiple species and in any preparation
      type/dosage/route of administration. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trials for eligibility and quality and extracted
      data. We resolved any disagreements through consensus. The quality of the
      evidence was assessed using the GRADE approach. MAIN RESULTS: Ten RCTs (1656
      participants) met our inclusion criteria, and pharmaceutical industry funded none
      of these trials. All trials used probiotics as adjuvant therapy to antifungal
      drugs. Probiotics increased the rate of short-term clinical cure (risk ratio (RR)
      1.14, 95% confidence interval (CI) 1.05 to 1.24, 695 participants, 5 studies, low
      quality evidence) and mycological cure (RR 1.06, 95% CI 1.02 to 1.10, 969
      participants, 7 studies, low quality evidence) and decreased relapse rate at one
      month (RR 0.34, 95% CI 0.17 to 0.68, 388 participants, 3 studies, very low
      quality evidence). However, this effect did not translate into a higher frequency
      of long-term clinical cure (one month after treatment: RR 1.07, 95% CI 0.86 to
      1.33, 172 participants, 1 study, very low quality evidence; three months after
      treatment: RR 1.30, 95% CI 1.00 to 1.70, 172 participants, one study, very low
      quality evidence) or mycological cure (one month after treatment: RR 1.26, 95% CI
      0.93 to 1.71, 627 participants, 3 studies, very low quality evidence; three
      months after treatment: RR 1.16, 95% CI 1.00 to 1.35, 172 participants, one
      study, very low quality evidence). Probiotics use did not increase the frequency
      of serious (RR 0.80, 95% CI 0.22 to 2.94; 440 participants, 2 studies, low
      quality evidence). We found no eligible RCTs for outcomes as time to first
      relapse, need for additional treatment at the end of therapy, patient
      satisfaction and cost effectiveness. AUTHORS' CONCLUSIONS: Low and very low
      quality evidence shows that, compared with conventional treatment, the use of
      probiotics as an adjuvant therapy could increases the rate of short-term clinical
      and mycological cure and decrease the relapse rate at one month but this did not
      translate into a higher frequency of long-term clinical or mycological cure.
      Probiotics use does not seem to increase the frequency of serious or non-serious
      adverse events. There is a need for well-designed RCTs with standardized
      methodologies, longer follow-up and larger sample size.

PMID- 29168559
TI  - Time to stop using uncuffed tracheal tubes in children?

PMID- 29168558
TI  - Outcomes in women undergoing robotic-assisted laparoscopic hysterectomy compared
      to conventional laparoscopic hysterectomy at a tertiary hospital in Western
      Australia.
AB  - BACKGROUND: Robotic-assisted laparoscopic hysterectomy (RALH) is associated with
      improved outcomes compared to open surgery in patients with endometrial cancer
      but data are conflicting when comparing RALH to conventional total laparoscopic
      hysterectomy (TLH). In October 2014, a RALH program was established in Perth,
      Western Australia. AIM: To compare outcomes in patients undergoing RALH with a
      matched cohort undergoing TLH. MATERIALS AND METHODS: A retrospective matched
      cohort study compared outcomes in 45 patients who underwent RALH with 45 controls
      who were patients treated with TLH. RESULTS: Mean operating time was longer in
      the RALH group compared to controls (75.42 min vs 53.18 min, mean difference
      22.24 min, P < 0.001, 95% Cl, 11.07-33.42). No differences were observed in mean
      pain scores (RALH 1.47 vs TLH 1.84 P = 0.31), mean parenteral and oral opioid use
      (RALH 14.3 mg and 42.4 mg vs TLH 17.5 mg and 52.57 mg, P = 0.42 and 0.42,
      respectively), and mean length of stay (RALH 1.51 vs TLH 1.67 days, P = 0.49).
      Two patients in the RALH group and one patient in the TLH group sustained
      iatrogenic bladder injuries (P = 0.62). CONCLUSION: The establishment of the RALH
      program at our institution appeared to be associated with equivalent morbidity,
      post-operative pain, opioid use and length of stay compared to conventional
      laparoscopy. A surgical learning curve for RALH was observed. Well-designed
      prospective studies are needed to further evaluate short- and long-term patient
      function, morbidity, quality of life and oncologic outcomes.

PMID- 29168560
TI  - Decision-making in response to respiratory veno-venous extracorporeal membrane
      oxygenation referrals: is current practice precise enough?

PMID- 29168561
TI  - Combination therapy with mifepristone and misoprostol for the management of first
      trimester miscarriage: Improved success.
AB  - BACKGROUND: First trimester miscarriage affects 20% of pregnancies. Medical
      management has a high degree of patient acceptance and does not increase the risk
      of infection. Mifepristone is an anti-progesterone shown to improve outcomes when
      used in conjunction with misoprostol for first trimester abortion. However, there
      have been conflicting results when it has been added to treatment regimens for
      miscarriage. METHODS: We performed a retrospective cohort analysis of women
      presenting to the Acute Gynaecology Service of our tertiary referral centre for
      miscarriage management from December 2010 until December 2013. Patients given
      misoprostol alone were compared to those who received combination treatment with
      mifepristone and misoprostol. Primary outcome was failure of treatment determined
      by the need for repeat medical management or surgical curettage. Secondary
      outcome was need for hospital admission. RESULTS: A total of 281 women were
      treated from December 2010 to December 2013: 179 received combined mifepristone
      and misoprostol and 102 received misoprostol only. The primary outcome was
      significantly different between the two groups; 73% of women in the mifepristone
      and misoprostol group required no further treatment compared to only 56% of women
      in the misoprostol only group (P = 0.012). There were fewer hospital admissions,
      with 24% in the combined therapy group being admitted compared to 42% in the
      misoprostol only group (P < 0.001). CONCLUSION: The addition of mifepristone to
      medical treatment regimens for first trimester miscarriage significantly
      decreased the need for repeat medical dosing and surgical curettage. Hospital
      admissions were also significantly decreased.

PMID- 29168562
TI  - Effect of quality and origin of technical sucrose solutions on the inclusion of
      colourants into the sugar crystal matrix.
AB  - BACKGROUND: Due to the liberalisation of the European sugar market the pressure
      to improve factory utilisation is growing. Currently, beet and cane as sucrose
      sources are produced in isolation, according to geography. Co-production of sugar
      from beet and cane origin in one stream is a promising option. However, the
      knowledge base for production sugar is practically non-existent. This paper is
      part of our contribution to this field and specifically addresses effects of raw
      material quality. RESULTS: This framework formulated for the colouring of sugars
      crystallised from mixed syrups is also valid for different raw material
      qualities: raw cane sugars: colour values 1221 to 2505 IU, dextran levels 50 to
      1200 mg kg-1 ; beet syrups: 1509 to 2058 IU. Co-crystallisation is the main
      colour incorporation mechanism. Colour due to liquid inclusion increases strongly
      at cane inclusion levels in excess of 60%. The prediction of final sugar colour
      based on characteristics of pure mixture constituents is verified and indicates
      significant differences to current recommendations. CONCLUSION: A first
      comprehensive description of the colour values in sugars produced from mixed cane
      and beet syrups is presented. Prediction of colour values from data on sugar
      colour of single sources marks a major contribution to future applications of co
      production. (c) 2017 Society of Chemical Industry.

PMID- 29168563
TI  - Pelvic examination may be meaningfully taught to novices and be used to predict
      operating times for laparoscopic excision of endometriosis in one surgical
      procedure.
AB  - OBJECTIVE: To investigate whether pelvic examination may be meaningfully taught
      to novice medical students and its accuracy in predicting operating times for
      laparoscopic excision of endometriosis at a single surgical procedure. METHODS:
      Women with suspected endometriosis scheduled for laparoscopy underwent pelvic
      examination to estimate operative time by medical students (novices), trainees,
      senior clinicians with <10 years surgical experience (experts) and >=10 years
      (masters). Examination and intraoperative findings were compared and stage of
      disease recorded. RESULTS: There were 138 estimations of operating time at the
      initial assessment and 251 estimations of operating time prior to surgery. The
      median surgical duration was 44 min (range 12-398) and increased progressively
      with revised American Society for Reproductive Medicine disease stage. Clinical
      predictions exceeded actual operating times by a median of 18 min (range
      overestimating by 180 min and underestimating by 120 min) with 80% of procedures
      completed in less time than predicted and none requiring a second procedure.
      There was no statistical difference in operative time estimations between the
      groups with students and trainees underestimating surgical duration by a median
      of two and five minutes, respectively, experts having a median time difference of
      zero minutes, and masters overestimating by 4.5 min. CONCLUSION: Targeted pelvic
      examining may be taught to novices (medical students) and can be used to predict
      operating time at one surgical procedure. Less experienced examiners have a
      tendency to underestimate surgical duration, with masters overestimating surgical
      time when scheduling laparoscopies for endometriosis, and increasing disease
      stage is associated with a less precise estimation of surgical duration.

PMID- 29168564
TI  - Grade-related differences in strategy use in multidigit division in two
      instructional settings.
AB  - We aimed to investigate upper elementary children's strategy use in the domain of
      multidigit division in two instructional settings: the Netherlands and Flanders
      (Belgium). A cross-sectional sample of 119 Dutch and 122 Flemish fourth to sixth
      graders solved a varied set of multidigit division problems. With latent class
      analysis, three distinct strategy profiles were identified: children consistently
      using number-based strategies, children combining the use of column-based and
      number-based strategies, and children combining the use of digit-based and number
      based strategies. The relation between children's strategy profiles and their
      instructional setting (country) and grade were generally in line with
      instructional differences, but large individual differences remained.
      Furthermore, Dutch children more frequently made adaptive strategy choices and
      realistic solutions than their Flemish peers. These results complement and refine
      previous findings on children's strategy use in relation to mathematics
      instruction. Statement of contribution What is already known? Mathematics
      education reform emphasizes variety, adaptivity, and insight in arithmetic
      strategies. Countries have different instructional trajectories for multidigit
      division. Mixed results on the impact of instruction on children's strategy use
      in multidigit division. What does this study add? Latent class analysis
      identified three meaningful strategy profiles in children from grades 4-6. These
      strategy profiles substantially differed between children. Dutch and Flemish
      children's strategy use is related to their instructional trajectory.

PMID- 29168565
TI  - Growth rates of pulmonary metastases after liver transplantation for unresectable
      colorectal liver metastases.
AB  - BACKGROUND: The previously reported SECA study demonstrated a dramatic 5-year
      survival improvement in patients with unresectable colorectal liver metastases
      (CLM) treated with liver transplantation (LT) compared with chemotherapy. The
      objective of this study was to assess whether immunosuppressive therapy
      accelerates the growth of pulmonary metastases in patients transplanted for
      unresectable CLM. METHODS: Chest CT scans from 11 patients in the SECA study
      resected for 18 pulmonary metastases were reviewed retrospectively. Tumour
      diameter, volume and CT characteristics were registered and tumour volume
      doubling time was calculated. Findings in the SECA group were compared with those
      of a control group consisting of 12 patients with non-transplanted rectal cancer
      resected for 26 pulmonary metastases. Disease-free survival (DFS) and overall
      survival (OS) after first pulmonary resection were determined. RESULTS: Median
      doubling time based on tumour diameter and volume in the SECA and control groups
      were 125 and 130 days (P = 0.658) and 110 and 129 days (P = 0.632) respectively.
      The metastases in both groups were distributed to all lung lobes and were mostly
      peripheral. Median DFS after LT in the SECA group and after primary pelvic
      surgery in the control group was 17 (range 6-42) and 18 (2-57) months
      respectively (P = 0.532). In the SECA group, estimated 5-year DFS and OS rates
      after first pulmonary resection were 39 and 51 per cent respectively. CONCLUSION:
      Patients treated by LT for unresectable CLM have a good prognosis following
      resection of pulmonary metastases. Doubling time did not appear to be worse with
      the immunosuppression used after LT.

PMID- 29168566
TI  - Comparison of subchronic immunotoxicity of four different types of aluminum-based
      nanoparticles.
AB  - Nanoparticles (NPs) have recently emerged as an inhalable pollutant, owing to
      their applications, aluminum-based NPs (Al-NPs) have been prioritized for
      toxicity testing. In the current study, we compared the pulmonary biopersistence
      and subsequent toxicity of four different types of Al-NPs (two rod-type aluminum
      oxide NPs [AlONPs] with different aspect ratios [short (S)- and long (L)-AlONPs],
      spherical aluminum cerium oxide NPs [AlCeO3 , AlCeONPs] and spherical gamma
      aluminum oxide hydroxide nanoparticles [AlOOHNPs]) 13weeks after a single
      intratracheal instillation, considering the importance of their properties in
      their toxicity. We found that the pulmonary biopersistence of Al-NPs was
      strengthened by a high aspect ratio in the rod-type AlONPs and by the presence of
      hydroxyl groups in the spherical-type Al-NPs. The highest toxicity was observed
      in the mice treated with AlOOHNPs, which showed low biostability. More
      importantly, we identified that the commercially available AlCeONPs were Al2 O3 
      coated CeO2 NPs, but not AlCeO3 NPs, although they have been sold under the trade
      name of AlCeONPs. In conclusion, the aspect ratio and biostability may be
      important factors in the determination of the biopersistence of NPs and the
      subsequent biological response. In addition, the physicochemical properties of
      NPs should be examined in detail before their release into the market to prevent
      unexpected adverse health effects.

PMID- 29168568
TI  - Acceptance and transfer to a regional severe respiratory failure and veno-venous
      extracorporeal membrane oxygenation (ECMO) service: predictors and outcomes.
AB  - The use of extracorporeal membrane oxygenation for respiratory failure is high
      risk and resource intensive. In England, five centres provide this service and
      patients who are referred have four possible outcomes: declined transfer due to
      perceived futility; accepted in principle but remain at the referring centre with
      ongoing surveillance; retrieved using conventional ventilation; or retrieved on
      extracorporeal support. The decision-making process leading to these outcomes has
      not previously been examined. We evaluated referrals to one centre and identified
      factors associated with each decision outcome. Five hundred and sixty-four
      patients were analysed from January 2012 to October 2015. One hundred and fifty
      seven patients were declined; multivariate analysis demonstrated associated
      factors to be: age (odds ratio (95% confidence interval) 1.05 (1.04-1.07));
      immunocompromise (4.95 (2.58-9.67)); lactate (1.11 (1.01-1.22)); duration of
      ventilation (1.08 (1.04-1.14)); and cardiac failure (3.22 (1.04-10.51)). Factors
      associated with the decision to retrieve an accepted patient were: plateau
      pressure (1.05 (1.01-1.10)); ratio of arterial oxygen partial pressure to
      fractional inspired oxygen (0.89 (0.85-0.93)); partial pressure of carbon dioxide
      in arterial blood (1.13 (1.03-1.25)); and the absence of non-pulmonary infection
      (0.31 (0.15-0.61)). Only pH was independently associated with the decision to
      transfer on extracorporeal support (0.020 (0.002-0.017)). Six-month survival in
      the declined, non-retrieved, conventionally retrieved and extracorporeal
      retrieved groups was 16.6%, 71.1%, 76.7% and 72.1%, respectively, substantially
      supporting the decision-making model. Survival in the accepted group exceeds that
      reported previously. However, a proportion of those declined do survive and some
      remotely managed patients die. This suggests the approach does not account for
      some important survival-determining factors.

PMID- 29168567
TI  - Preparation and mechanism analysis of an environment-friendly maize seed coating
      agent.
AB  - BACKGROUND: Traditional seed coating agents often contain toxic ingredients,
      which contaminate the environment and threaten human health. This paper expounds
      a method of preparing a novel environment-friendly seed coating agent for maize
      and researches its mechanism of action. The natural polysaccharide polymer, which
      is the main active ingredient of this environment-friendly seed coating agent,
      has the characteristics of innocuity and harmlessness, and it can replace the
      toxic ingredients used in traditional seed coating agents. RESULTS: This
      environment-friendly seed coating agent for maize was mainly made up of the
      natural polysaccharide polymer and other additives. The field trials results
      showed that the control efficacy of Helminthosporium maydis came to 93.72%, the
      anti-feeding rate of cutworms came to 81.29%, and the maize yield was increased
      by 17.75%. Besides, the LD50 value (half the lethal dose in rats) of this seed
      coating agent was 10 times higher than that of the traditional seed coating
      agents. This seed coating agent could improve the activity of plant protective
      enzymes (peroxidase, catalase and superoxidase dismutase) and increase the
      chlorophyll content. CONCLUSION: This seed coating agent has four characteristics
      of disease prevention, desinsectization, increasing yield and safety. Results of
      mechanism analyses showed that this seed coating agent could enhance disease
      control effectiveness by improving plant protective enzymes activity and increase
      maize yield by improving chlorophyll content. (c) 2017 Society of Chemical
      Industry.

PMID- 29168569
TI  - Point-of-use fortification of foods with micronutrient powders containing iron in
      children of preschool and school-age.
AB  - BACKGROUND: Approximately 600 million children of preschool and school age are
      anaemic worldwide. It is estimated that at least half of the cases are due to
      iron deficiency. Point-of-use fortification of foods with micronutrient powders
      (MNP) has been proposed as a feasible intervention to prevent and treat anaemia.
      It refers to the addition of iron alone or in combination with other vitamins and
      minerals in powder form, to energy-containing foods (excluding beverages) at home
      or in any other place where meals are to be consumed. MNPs can be added to foods
      either during or after cooking or immediately before consumption without the
      explicit purpose of improving the flavour or colour. OBJECTIVES: To assess the
      effects of point-of-use fortification of foods with iron-containing MNP alone, or
      in combination with other vitamins and minerals on nutrition, health and
      development among children at preschool (24 to 59 months) and school (five to 12
      years) age, compared with no intervention, a placebo or iron-containing
      supplements. SEARCH METHODS: In December 2016, we searched the following
      databases: CENTRAL, MEDLINE, Embase, BIOSIS, Science Citation Index, Social
      Science Citation Index, CINAHL, LILACS, IBECS, Popline and SciELO. We also
      searched two trials registers in April 2017, and contacted relevant organisations
      to identify ongoing and unpublished trials. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) and quasi-RCTs trials with either individual or cluster
      randomisation. Participants were children aged between 24 months and 12 years at
      the time of intervention. For trials with children outside this age range, we
      included studies where we were able to disaggregate the data for children aged 24
      months to 12 years, or when more than half of the participants were within the
      requisite age range. We included trials with apparently healthy children;
      however, we included studies carried out in settings where anaemia and iron
      deficiency are prevalent, and thus participants may have had these conditions at
      baseline. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      the eligibility of trials against the inclusion criteria, extracted data from
      included trials, assessed the risk of bias of the included trials and graded the
      quality of the evidence. MAIN RESULTS: We included 13 studies involving 5810
      participants from Latin America, Africa and Asia. We excluded 38 studies and
      identified six ongoing/unpublished trials. All trials compared the provision of
      MNP for point-of-use fortification with no intervention or placebo. No trials
      compared the effects of MNP versus iron-containing supplements (as drops, tablets
      or syrup).The sample sizes in the included trials ranged from 90 to 2193
      participants. Six trials included participants younger than 59 months of age
      only, four included only children aged 60 months or older, and three trials
      included children both younger and older than 59 months of age.MNPs contained
      from two to 18 vitamins and minerals. The iron doses varied from 2.5 mg to 30 mg
      of elemental iron. Four trials reported giving 10 mg of elemental iron as sodium
      iron ethylenediaminetetraacetic acid (NaFeEDTA), chelated ferrous sulphate or
      microencapsulated ferrous fumarate. Three trials gave 12.5 mg of elemental iron
      as microencapsulated ferrous fumarate. Three trials gave 2.5 mg or 2.86 mg of
      elemental iron as NaFeEDTA. One trial gave 30 mg and one trial provided 14 mg of
      elemental iron as microencapsulated ferrous fumarate, while one trial gave 28 mg
      of iron as ferrous glycine phosphate.In comparison with receiving no intervention
      or a placebo, children receiving iron-containing MNP for point-of-use
      fortification of foods had lower risk of anaemia prevalence ratio (PR) 0.66, 95%
      confidence interval (CI) 0.49 to 0.88, 10 trials, 2448 children; moderate-quality
      evidence) and iron deficiency (PR 0.35, 95% CI 0.27 to 0.47, 5 trials, 1364
      children; moderate-quality evidence) and had higher haemoglobin (mean difference
      (MD) 3.37 g/L, 95% CI 0.94 to 5.80, 11 trials, 2746 children; low-quality
      evidence).Only one trial with 115 children reported on all-cause mortality (zero
      cases; low-quality evidence). There was no effect on diarrhoea (risk ratio (RR)
      0.97, 95% CI 0.53 to 1.78, 2 trials, 366 children; low-quality evidence).
      AUTHORS' CONCLUSIONS: Point-of-use fortification of foods with MNPs containing
      iron reduces anaemia and iron deficiency in preschool- and school-age children.
      However, information on mortality, morbidity, developmental outcomes and adverse
      effects is still scarce.

PMID- 29168570
TI  - Specific immunotherapy in local allergic rhinitis: A randomized, double-blind
      placebo-controlled trial with Phleum pratense subcutaneous allergen
      immunotherapy.
AB  - BACKGROUND: Allergen immunotherapy has been shown to be an effective treatment
      for local allergic rhinitis (LAR) to house dust mites. Studies with pollen
      allergen immunotherapy are limited to observational studies. The aim of this
      study was to evaluate the clinical efficacy and safety of Phleum pratense
      subcutaneous immunotherapy (Phl-SCIT) in LAR. METHODS: In a randomized double
      blind placebo-controlled study, 56 patients with moderate-severe LAR to grass
      pollen received Phl-SCIT with a depigmented polymerized pollen vaccine or placebo
      for the first year, and Phl-SCIT the second one. The blind was maintained
      throughout the study. Primary outcome was combined symptom medication score
      (CSMS) during grass pollen season (GPS). Secondary clinical outcomes included
      organ-specific symptoms, medication-free days, rhinitis severity and asthma
      control. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal allergen
      provocation test (NAPT), skin testing, serum levels of specific IgG4 and specific
      IgE and safety were also evaluated. RESULTS: Subcutaneous immunotherapy (SCIT)
      had a short-term and sustained effect with significant improvements of all
      primary and secondary clinical outcomes and RQLQ score. SCIT significantly
      increased serum sIgG4 levels and allergen tolerance, from the 6th to 24th months
      of treatment. At the end of the study, 83% of patients treated with >=6 months of
      SCIT tolerated a concentration of P. pratense over 50 times higher than baseline,
      and 56% gave a negative NAPT. SCIT was well tolerated; six mild local reactions
      occurred, and there were no serious adverse events related to the study
      medication. CONCLUSIONS: Subcutaneous immunotherapy with depigmented polymerized
      allergen extracts is a safe and clinically effective treatment for LAR to P.
      pratense.

PMID- 29168571
TI  - Erratum.

PMID- 29168572
TI  - Withdrawal of Expression of Concern.

PMID- 29168573
TI  - Oral health status among children and adolescents in governmental and private
      schools of the Palestinian Territories.
AB  - BACKGROUND: Political conflicts in the Palestinian Territories (PT) have resulted
      in systematic deterioration of socio-economic conditions and health. The World
      Health Organization (WHO) has emphasised the negative impacts of social crisis on
      children' oral health and quality of life. OBJECTIVES: To assess the prevalence
      and trends in dental caries and poor gingival health of schoolchildren in the PT
      through the scholastic years 1998/1999 to 2012/2013. METHODS: This is a
      retrospective study. Prevalence data on dental caries of primary and permanent
      dentitions among children 6, 12 and 16 years of age were gathered from annual
      oral health reports of the School Dental Health Programme (SDHP)-Ministry of
      Health. Caries was recorded according to WHO methods and criteria. Decayed,
      missing and filled teeth indices for primary (dmft) and permanent (DMFT) teeth
      were calculated. Gingival health status was examined according to the Community
      Periodontal Index (scores 1 and 2). Statistical analysis used SPSS. RESULTS: In
      2012/2013, dental caries prevalence rates and the index scores among
      schoolchildren were as follows, respectively: 56.4% and 2.7 dmft at age 6; 42.0%
      and 1.4 DMFT at age 12; and 38.7% and 1.7 DMFT at age 16. For all age groups, the
      d/D-component of the caries indices was high. Trends of dental-caries prevalence,
      caries experience and gingival bleeding were fairly constant over time from
      1998/1999. CONCLUSION: The SDHP was established in order to prevent and control
      oral diseases among schoolchildren in the PT. The Programme is fairly passive and
      the survey indicates an urgent need for reorientation of activities towards
      population-based prevention and health promotion. The application of the WHO
      Health Promoting Schools concept is highly recommended.

PMID- 29168574
TI  - Dental enamel defect diagnosis through different technology-based devices.
AB  - INTRODUCTION: Dental enamel defects (DEDs) are faulty or deficient enamel
      formations of primary and permanent teeth. Changes during tooth development
      result in hypoplasia (a quantitative defect) and/or hypomineralisation (a
      qualitative defect). OBJECTIVE: To compare technology-based diagnostic methods
      for detecting DEDs. MATERIAL AND METHODS: Two-hundred and nine dental surfaces of
      anterior permanent teeth were selected in patients, 6-11 years of age, with cleft
      lip with/without cleft palate. First, a conventional clinical examination was
      conducted according to the modified Developmental Defects of Enamel Index (DDE
      Index). Dental surfaces were evaluated using an operating microscope and a
      fluorescence-based device. Interexaminer reproducibility was determined using the
      kappa test. To compare groups, McNemar's test was used. Cramer's V test was used
      for comparing the distribution of index codes obtained after classification of
      all dental surfaces. RESULTS: Cramer's V test revealed statistically significant
      differences (P < .0001) in the distribution of index codes obtained using the
      different methods; the coefficients were 0.365 for conventional clinical
      examination versus fluorescence, 0.961 for conventional clinical examination
      versus operating microscope and 0.358 for operating microscope versus
      fluorescence. The sensitivity of the operating microscope and fluorescence method
      was statistically significant (P = .008 and P < .0001, respectively). Otherwise,
      the results did not show statistically significant differences in accuracy and
      specificity for either the operating microscope or the fluorescence methods.
      CONCLUSION: This study suggests that the operating microscope performed better
      than the fluorescence-based device and could be an auxiliary method for the
      detection of DEDs.

PMID- 29168575
TI  - Cuffed vs. uncuffed tracheal tubes in children: a randomised controlled trial
      comparing leak, tidal volume and complications.
AB  - Cuffed tracheal tubes are increasingly used in paediatric anaesthetic practice.
      This study compared tidal volume and leakage around cuffed and uncuffed tracheal
      tubes in children who required standardised mechanical ventilation of their lungs
      in the operating theatre. Children (0-16 years) undergoing elective surgery
      requiring tracheal intubation were randomly assigned to receive either a cuffed
      or an uncuffed tracheal tube. Assessments were made at five different time
      points: during volume-controlled ventilation 6 ml.kg-1 , PEEP 5 cmH2 O and during
      pressure-controlled ventilation 10 cmH2 O / PEEP 5 cmH2 O. The pressure
      controlled ventilation measurement time-points were: just before a standardised
      recruitment manoeuvre; just after recruitment manoeuvre; 10 min; and 30 min after
      the recruitment manoeuvre. Problems and complications were recorded. During
      volume-controlled ventilation, leakage was significantly less with cuffed
      tracheal tubes than with uncuffed tracheal tubes; in ml.kg-1 , median (IQR
      [range]) 0.20 (0.13-0.39 [0.04-0.60]) vs. 0.82 (0.58-1.38 [0.24-4.85]),
      respectively, p < 0.001. With pressure-controlled ventilation, leakage was less
      with cuffed tracheal tubes and stayed unchanged over a 30-min period, whereas
      with uncuffed tracheal tubes, leakage was higher and increased further over the
      30-min period. Tidal volumes were higher in the cuffed group and increased over
      time, but in the uncuffed group were lower and decreased over time. Both groups
      showed an increase in tidal volumes following recruitment manoeuvres. There were
      more short-term complications with uncuffed tracheal tubes, but no major
      complications were recorded in either group at long-term follow-up. With
      standardised ventilator settings, cuffed tracheal tubes produced better
      ventilation characteristics compared with uncuffed tracheal tubes during general
      anaesthesia for routine elective surgery.

PMID- 29168576
TI  - Clinical value of peripheral blood microRNA detection in evaluation of SOX
      regimen as neoadjuvant chemotherapy for gastric cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy has been widely applied in treating advanced
      gastric cancer (GC). However, little research has been conducted on evaluating
      the effect of neoadjuvant chemotherapy. Purpose of this study was to evaluate the
      effect of SOX regimen as neoadjuvant chemotherapy by detecting some microRNAs.
      METHODS: Total 120 GC patients who had received neoadjuvant chemotherapy (SOX
      regimen) were recruited with 100 healthy participants as control contemporarily.
      Age and gender have no significant difference in both groups (P > .05). The
      effect of chemotherapy was evaluated by the results of CT scan and surgery. Also,
      adverse effects of chemotherapy were documented. Peripheral blood of GC patients
      was collected twice: one day before chemotherapy and surgery, respectively,
      whereas healthy controls' peripheral blood was collected once. Quantitative real
      time PCR (qPCR) was utilized to detect expression of miR-145, miR-185, miR-381,
      and miR-195 of peripheral blood in both groups. RESULTS: One hundred and twenty
      patients with advanced GC completed a total of 386 cycles of neoadjuvant
      chemotherapy with effective rate at 84.17% (101 of 120). Expression of miR-145,
      miR-185, and miR-381 of patients with GC was lower than that in the control group
      before chemotherapy commence (all P < .05), while the expressions of miR-145 and
      miR-185 elevated noticeably in CG patients after neoadjuvant chemotherapy (P <
      .05). The differences in the expression of miR-145 and miR-185 in advanced GC
      patients with different chemotherapy outcomes were detected. CONCLUSION: Patients
      with GC at advanced stages had aberrant miRs expressions. Detection of miR-145
      and miR-185 expression may assist to predict effectiveness and adverse effects of
      SOX regimen as neoadjuvant chemotherapy.

PMID- 29168578
TI  - Utilization of community health workers in Canada's Children's Oral Health
      Initiative for indigenous communities.
AB  - OBJECTIVE: The Children's Oral Health Initiative (COHI) is a federally funded
      community-based preventive dental programme implemented in geographically remote
      Canadian Indigenous communities. The study investigated the effect of the
      availability of local community health workers (COHI Aides) on access to the
      programme's preventive dental services for children. METHODS: Twenty-five
      communities were continuously enrolled in the COHI during the 7-year study
      period. Communities were categorized as having uninterrupted (all 7 years),
      intermittent (>=4 years) or sporadic (<4 years) service from a community health
      worker. Four outcome variables measured longitudinal changes in access to
      preventive dental services: (i) the number of enrolments; (ii) the number of
      enrolled children with multiple fluoride varnishes delivered; (iii) the number of
      enrolled children with sealants placed; and (iv) the number of enrolled children
      receiving ART. RESULTS: The general longitudinal trend for programme enrolment
      and each of the preventive dental service delivery outcomes was similar. Children
      in communities with uninterrupted service tended to have the highest rates of
      enrolment and service delivery, which remained constant over time. Children in
      communities with sporadic service tended to have persistently low rates of
      enrolment and service delivery over the study period. CONCLUSIONS: Community
      health workers were beneficial in promoting programme enrolment, as well as
      facilitating and augmenting the delivery of preventive dental services.

PMID- 29168577
TI  - Screening for developmental dysplasia of the hip in a rural health district: An
      analysis of practice.
AB  - OBJECTIVE: To describe hip dysplasia screening practices in a local rural health
      district. DESIGN: Cross-sectional study of hospital birth records, local
      physiotherapy records, public community health electronic medical record
      (Community Health Information Management Enterprise database) and a survey of
      local clinicians who work with infants and children. SETTING: Three rural public
      hospitals and community health centres in a New South Wales health district.
      PARTICIPANTS: Birth records (n = 196) from March 2012 to May 2012; attendance at
      child and family nurse checks (n = 788) May 2013-April 2014; 13 cases of managed
      developmental dysplasia of the hip (DDH) 2012 and local clinicians (n = 49).
      RESULTS: At birth, the majority of infants (91%, 179/196) had documented hip
      screening. Community health records show this dropped to 75% (587/788) at 1-4
      weeks and 29% (227/788) at 6-8 weeks. A survey of local clinicians (54% response
      rate; 49/91) revealed most (78%) screen for DDH and less than half (43%) use
      guidelines. Almost all (97%) clinicians reported screening for DDH at 6-8 weeks
      of age. Only 51% of clinicians reported having specific training for DDH
      screening and 76% would like further training. The rate of late DDH requiring
      management in 2012 was 0.87% (7/806) and the rate of late DDH requiring surgery
      was 0.25% (2/806). CONCLUSION: DDH screening practices are well established at
      birth in the rural health district. There is variability in DDH screening
      practices beyond 8 weeks of age. Clinicians report variations in their knowledge
      and training. Training in DDH screening and hip screening prompts added to the
      personal health record might improve rates of DDH screening beyond 8 weeks of
      age.

PMID- 29168579
TI  - Organocatalyzed Decarboxylative Trichloromethylation of Morita-Baylis-Hillman
      Adducts in Batch and Continuous Flow.
AB  - Two protocols for the organocatalyzed decarboxylative trichloromethylation of
      Morita-Baylis-Hillman (MBH) substrates have been developed. Applying sodium
      trichloroacetate, as the trichloromethyl anion precursor, in combination with an
      organocatalyst and acetylated MBH-alcohols, the desired trichloromethylated
      products were obtained in good yields at room temperature in batch. The method
      was next extrapolated into a two-step continuous flow protocol, starting directly
      from the MBH alcohols, in combination with tributylamine acting both as base and
      catalyst. The flow process proved superior to the batch approach, reducing the
      reaction time from 16 hours to only 20 minutes, with increased yields for all
      investigated entries. Two examples were also taken to scale-up in flow producing
      more than 10 grams of both trichloromethylated targets. Finally, substitution of
      the organocatalyst to (DHQ)2 PHAL or (DHQD)2 PHAL induced chiral transfer to the
      generated stereocenter in the reaction attaining selectivities with nearly 90 %
      ee.

PMID- 29168581
TI  - Dopamine oxidation mediates a time-dependent pathological cascade in Parkinson's
      disease.

PMID- 29168580
TI  - Resveratrol, pterostilbene, and dementia.
AB  - Resveratrol is a natural phytoestrogen with neuroprotective properties.
      Polyphenolic compounds including resveratrol exert in vitro antioxidant, anti
      inflammatory, and antiamyloid effects. Resveratrol and its derivative
      pterostilbene are able to cross the blood-brain barrier and to influence brain
      activity. The present short review summarizes the available evidence regarding
      the effects of these polyphenols on pathology and cognition in animal models and
      human subjects with dementia. Numerous investigations in cellular and mammalian
      models have associated resveratrol and pterostilbene with protection against
      dementia syndromes such as Alzheimer's disease (AD) and vascular dementia. The
      neuroprotective activity of resveratrol and pterostilbene demonstrated in in
      vitro and in vivo studies suggests a promising role for these compounds in the
      prevention and treatment of dementia. In comparison to resveratrol, pterostilbene
      appears to be more effective in combatting brain changes associated with aging.
      This may be attributed to the more lipophilic nature of pterostilbene with its
      two methoxyl groups compared with the two hydroxyl groups of resveratrol. The
      findings of available intervention trials of resveratrol in individuals with mild
      cognitive impairment or AD do not provide evidence of neuroprotective or
      therapeutic effects. Future clinical trials should be conducted with long-term
      exposure to preparations of resveratrol and pterostilbene with high
      bioavailability. (c) 2017 BioFactors, 44(1):83-90, 2018.

PMID- 29168582
TI  - Diagnostic value of trait antinuclear antibodies and multiple immunoglobulin
      production in autoimmune diseases.
AB  - BACKGROUND: Our article aims to evaluate the proportion of monospecific
      antinuclear antibodies (ANA) and polyclonal ANAs in patients with autoimmune
      diseases based on the results of an ANA panel and to evaluate the efficiency of
      trait ANAs as a novel diagnostic tool. This study also aims to investigate
      immunoglobulin production in autoimmune diseases by detecting different
      antibodies. METHODS: The serum ANA profile of 634 patients with autoimmune
      diseases was analyzed using the immunoblot method. A specific formula was
      developed in an effort to calculate the theoretical proportion of monospecific
      ANA (TPM) in different disease groups. Different IgM, IgG, and IgE variants for
      several pathologies were detected. RESULTS: The observed proportions of
      monospecific ANAs (OPM) were all lower than the predicted TPM in autoimmune
      diseases. Polyclonal ANAs were predominant in patients with systemic lupus
      erythematosus (SLE). There were statistical differences in OPM and TPM in all
      disease groups (P < .001). Receiver operating characteristic curve (ROC curve)
      analysis of trait ANAs between the SLE group and the control groups indicated an
      area under the curve of 0.916. Differences were found in IgM of Toxoplasma gondii
      (TOXO) and IgG of hepatitis C virus (HCV) and Treponema pallidum (TP) when
      comparing the various disease groups to the control group. CONCLUSION: The higher
      TPM suggests that polyclonal differentiation is the major mechanism of ANA in
      autoimmune diseases. Trait ANA is potentially a valuable new index for diagnosis
      in SLE. Further investigation is needed to understand the link between B-cell
      differentiation and autoimmune diseases.

PMID- 29168583
TI  - Distinct patterns of amyloid-dependent tau accumulation in Lewy body diseases.
AB  - BACKGROUND: In addition to Lewy body pathology, amyloid-beta plaques and
      neurofibrillary tangles that are characteristic for Alzheimer's disease are also
      frequently found in Lewy body diseases. OBJECTIVES: The objective of this study
      was to investigate tau accumulation patterns in dementia with Lewy bodies and
      other Lewy body diseases using in vivo 18 F-AV-1451 PET. METHODS: The study
      included 12 Parkinson's disease (PD) patients with normal cognition, 22 PD
      patients with cognitive impairment, and 18 dementia with Lewy bodies patients. In
      addition, 25 Alzheimer's disease patients and 25 healthy controls were included
      for comparison. All participants underwent 18 F-AV-1451 and 18 F-florbetaben PET
      scans, and cortical binding values were compared between the controls and each
      disease group. RESULTS: When compared with the controls, dementia with Lewy
      bodies patients showed slightly increased 18 F-AV-1451 binding in the primary
      sensorimotor and visual cortices and the parieto-temporal cortices, which failed
      to survive multiple comparisons. Amyloid-positive dementia with Lewy bodies
      patients showed significantly increased binding in the same regions when compared
      with controls, and even greater binding in the primary sensorimotor and visual
      cortices than Alzheimer's disease. Meanwhile, binding in the lateral and medial
      temporal cortices was less prominent than in Alzheimer's disease. In dementia
      with Lewy bodies, 18 F-AV-1451 binding in the occipital cortex correlated with 18
      F-florbetaben binding. Amyloid-negative patients with normal cognition, patients
      with cognitive impairment, and dementia with Lewy bodies patients did not show
      increased 18 F-AV-1451 binding. CONCLUSIONS: Dementia with Lewy bodies patients
      may harbor 18 F-AV-1451 binding patterns distinct from Alzheimer's disease, with
      greater involvement of the primary cortices and less involvement of the temporal
      cortex. Tau burden increases in the Lewy body disease spectrum, and amyloid may
      play an important role in the accumulation of neocortical tau in Lewy body
      diseases. (c) 2017 International Parkinson and Movement Disorder Society.

PMID- 29168584
TI  - Hemolysis and IgA-antibodies against tissue transglutaminase: When are antibody
      test results no longer reliable?
AB  - BACKGROUND: Antibodies against tissue transglutaminase (TTG) of isotype IgA (IgA
      aTTG) represent reliable diagnostic markers to confirm or exclude celiac disease
      (CD). Hemolysis (HL) is an important pre-analytical factor. HL can be quantified
      as HL index (HI) correlating with the concentration of free hemoglobin. TTG is
      abundant in erythrocytes and released upon HL. In immunoassays, the released TTG
      may interfere with binding of IgA-aTTG to the coated TTG. METHODS: We selected 17
      HL-free sera from children with biopsy-confirmed CD: 7 with low-positive (1-5
      multiples of upper limit of normal [*ULN]), 5 with intermediate (5-10 * ULN) and
      5 with high IgA-aTTG (10-15 * ULN). Sera were spiked with hemolysates resulting
      in HIs ranging from 12.5 to 800 (12.5-800 mg/dL free hemoglobin). RESULTS: IgA
      aTTG values were significantly decreased (>10%) after addition of hemolysates
      even if HL was invisible (HI <50). This effect is diagnosis-relevant if IgA-aTTG
      values are measured just below the cut-offs: (i) 0.4-1 * ULN at HI >=25 (CD not
      excludable) and (ii) 8.5-10 * ULN at HI >=200 (diagnosis of CD without biopsy not
      possible). Antibodies against deamidated gliadin were not influenced by HL.
      CONCLUSIONS: IgA-aTTG results in sera with HI >=25 can yield inconclusive
      results. Therefore, those antibody results should be assessed only under
      consideration of the HI.

PMID- 29168585
TI  - The prognostic impact of serum bilirubin in stage IV colorectal cancer patients.
AB  - BACKGROUND: Bilirubin played a great role in antioxidation and anticancer and has
      been considered as a promising prognostic factor of non-liver disease-related
      death in various cancers. The aim of this study was to assess the prognostic
      value of pre-treatment serum bilirubin in stage IV CRC patients. METHODS: Serum
      bilirubin including TBIL, DBIL, and IBI which were tested at pre-treatment were
      investigated in 154 stage IV CRC patients in Zhongda Hospital, Nanjing, China,
      from July 2005 to July 2011. X-tile program was used to determine the optimal cut
      off values of these three biomarkers. Kaplan-Meier analysis, univariate, and
      multivariate cox regression as well as time-dependent ROC curve analysis were
      performed to evaluate the relations between serum bilirubin and survival
      outcomes. RESULTS: We got the results that the optimal cut-off points of serum
      TBIL, DBIL, and IBI levels were 12.9, 6.1, and 4.8 MUmol/L, respectively.
      Univariate analysis showed that elevated TBIL, DBIL, and CEA were significantly
      associated with poor 5-year OS in stage IV CRC patients. Multivariate cox
      analysis indicated that the high DBIL (HR=1.603, 95%CI=1.053-2.442, P<.028) and
      CEA (HR=1.785, 95%CI=1.123-2.837, P=.014) could be identified as independent
      factors for poor OS. Furthermore, time-dependent ROC curves demonstrated that
      high DBIL had similar prognostic efficacy as elevated CEA for poor OS (AUC=0.63
      and 0.61, respectively). CONCLUSIONS: Pre-treatment elevated TBIL and DBIL levels
      were associated with poor OS in stage IV CRC patients. Moreover, DBIL could be
      considered as an independent prognostic biomarker for OS. Furthermore, DBIL had
      similar prognostic efficacy as CEA for OS.

PMID- 29168586
TI  - Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood
      brain barrier disruption in a murine model of osmotic demyelination syndrome.
AB  - The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder
      of the central nervous system myelin that is often associated with a precipitous
      rise of serum sodium concentration. To investigate the physiopathology of ODS in
      vivo, we generated a novel murine model based on the abrupt correction of chronic
      hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory
      evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte
      markers (APC and Cx47) were downregulated, prior to any detectable demyelination.
      Oligodendrocytopathy was temporally and spatially correlated with the loss of
      astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will
      develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at
      the ultrastructural level and culminated with necroptotic cell death, as
      demonstrated by pMLKL immunoreactivity. At 48 hr post-correction, ODS brains
      contained pathognomonic demyelinating lesions in the pons, mesencephalon,
      thalamus and cortical regions. These damages were accompanied by blood-brain
      barrier (BBB) leakages. Expression levels of IL-1beta, FasL, TNFRSF6 and LIF
      factors were significantly upregulated in the ODS lesions. Quiescent microglial
      cells type A acquired an activated type B morphology within 24 hr post
      correction, and reached type D at 48 hr. In conclusion, this murine model of ODS
      reproduces the CNS demyelination observed in human pathology and indicates
      ambiguous causes that is regional vulnerability of oligodendrocytes and
      astrocytes, while it discards BBB disruption as a primary cause of demyelination.
      This study also raises new queries about the glial heterogeneity in susceptible
      brain regions as well as about the early microglial activation associated with
      ODS.

PMID- 29168588
TI  - Ovarian response to controlled ovarian stimulation for fertility preservation
      before oncology treatment: A retrospective cohort of 157 patients.
AB  - This is a retrospective cohort study aiming to examine the response of oncology
      patients undergoing controlled ovarian stimulation (COS) for fertility
      preservation and to review the incidence of short-term complications. The study
      group consisted by all oncology patients undergoing ovarian stimulation for
      fertility preservation (n = 157) between April 2009 and April 2016. Patients
      undergoing COS for IVF/ICSI for male factor only infertility in the same time
      period (n = 2,128) provided a comparator group. Oncology patients underwent COS
      to retrieve eggs for storage and future use. The cancer patients had a very
      similar distribution of oocyte yield to the comparator group. Those with ovarian
      cancer did have significantly lower oocyte recovery than those with other cancers
      (age-adjusted difference 7, 95% CI: 2-12). None of the patients in the study
      group were admitted with ovarian hyperstimulation syndrome or any other
      complication of COS or oocyte retrieval. This is one of the largest reported
      cohorts of patients treated for fertility preservation before oncology treatment.
      Our data have demonstrated a good response to stimulation, offering a reasonable
      chance of pregnancy in the future. In contrast to previous studies, we have
      demonstrated a similar number of oocytes retrieved to that of women undergoing
      IVF/ICSI treatment for male factor infertility.

PMID- 29168587
TI  - Effect of secondary penicillin prophylaxis on valvular changes in patients with
      rheumatic heart disease in Far North Queensland.
AB  - OBJECTIVE: To determine the effect of secondary penicillin prophylaxis on
      echocardiographic diagnosed valvular changes in patients with rheumatic heart
      disease or history of acute rheumatic fever in the Townsville Health district.
      DESIGN: Patients with known were identified from the North Queensland register,
      serial echocardiogram results and number of secondary penicillin prophylaxis
      doses received in 2014 were collated. Descriptive statistics were utilised.
      SETTING: Townsville Hospital and outreach clinics within the Townsville Health
      catchment zone. PARTICIPANTS: All patients diagnosed with acute rheumatic fever
      or rheumatic heart disease between 2010 and October 2013 who had serial
      echocardiograms prior to and post commencement of secondary penicillin
      prophylaxis were included. All patients were of Aboriginal or Torres Strait
      Islander descent. MAIN OUTCOME MEASURE: Progression of echocardiographic valvular
      changes and association with secondary penicillin prophylaxis compliance.
      Compliance with secondary penicillin prophylaxis among the study population was a
      secondary outcome measure. RESULTS: Twenty-three patients were recruited. Only
      those patients who were compliant with secondary penicillin prophylaxis had any
      improvement in valvular changes on echocardiogram. Four of six patients without
      any baseline valvular involvement developed new valvular changes. Seventy percent
      of patients received >75% of secondary penicillin prophylaxis doses. CONCLUSIONS:
      This small study of patients in Townsville suggests that with good secondary
      penicillin prophylaxis compliance there is regression of some cardiac lesions
      over time in people with rheumatic heart disease. Furthermore the natural history
      of acute rheumatic fever in the Indigenous population is progressive requiring
      strict adherence to secondary penicillin prophylaxis. Prospective studies or use
      of data from the nationwide RHD register and standardised reporting of cardiac
      echocardiograms will provide more robust evidence.

PMID- 29168589
TI  - Time to delivery: Transfers for threatened preterm labour and prelabour rupture
      of membranes in Western Australia.
AB  - OBJECTIVE: To describe the outcomes of patients transferred to King Edward
      Memorial Hospital (KEMH) with signs of labour at preterm gestations. DESIGN: A
      retrospective observational study of the 69 cases transferred to KEMH during
      2015. SETTING: Patient transfers from all locations across Western Australia (WA)
      to the sole tertiary perinatal centre in Perth. PARTICIPANTS: Pregnant women
      within WA with threatened or actual preterm labour (PTL) or preterm prelabour
      rupture of membranes (PPROM) between 23 and 32 weeks gestation. MAIN OUTCOME
      MEASURES: The occurrence of delivery during the admission and time-to-delivery as
      well as length of admission and association between clinical factors and time-to
      delivery. RESULTS: The percentage of the study population delivered during the
      admission following transfer was 72.5%. Eighty-six per cent of those who
      delivered did so within 72 hours of transfer. The median time from transfer to
      delivery was 1 day. Sixty-three per cent of those who did not deliver during the
      admission progressed to 36 weeks gestation. Patients transferred with PPROM were
      less likely to deliver during the admission compared to those with uterine
      activity (50% versus 19.6%, P = 0.007) and nulliparas were more likely to deliver
      (93.5% versus 55.3%, P < 0.001). CONCLUSION: The majority of women transferred
      with signs of PTL progress to delivery during the same admission with the highest
      risk of delivery being the first 72 hours following transfer. If the pregnancy is
      ongoing at 72 hours, there is a reasonable chance of progression to late preterm
      gestation supporting the return of woman to their place of origin for antenatal
      care following discharge.

PMID- 29168590
TI  - Clustering patterns of oral and general health-risk behaviours in Brazilian
      adolescents: Findings from a national survey.
AB  - OBJECTIVES: To evaluate how oral and general health-risk behaviours cluster among
      Brazilian adolescents. METHODS: The study comprised a total of 109 104
      adolescents (52.2% female) participating in the Brazilian National School-based
      Student Health Survey (PeNSE). Seventeen behaviours (including diet; oral and
      hand hygiene; frequency of dental visits; tobacco, alcohol and drug use; sexual
      behaviour; physical activity, and risk for external causes) were measured using a
      self-reported questionnaire. Pairwise correlations between the health-risk
      behaviours were performed, and clustering was assessed by the hierarchical
      agglomerative cluster analysis (HACA), which was used to identify stable cluster
      solutions of the health-risk behaviours. RESULTS: All health-risk behaviours were
      correlated with at least 1 behaviour (P < .01). HACA indicated 2 broad stable
      clusters (n = 105 604). The first cluster included current smoking, illegal drug
      use, no hand washing before meals, unprotected sex, no helmet use, less frequent
      toothbrushing, no seatbelt use, physical fighting, skipping breakfast, current
      drinking, high sugar intake and, at the final stage, no dental visits. The second
      cluster included insufficient physical activity, eating while watching TV or
      studying, and low fruit intake. CONCLUSIONS: The health-risk behaviours clustered
      into 2 specific patterns among Brazilian adolescents. One cluster gathered a
      combination of lack of adherence to preventive behaviours and the undertaking of
      risky conduct, while the second reflected an unhealthy lifestyle (sedentary
      habits and low fruit diet). Knowledge about the clustering patterns of oral and
      general health behaviours in adolescents can better direct the integration of
      oral and general health promotion interventions.

PMID- 29168591
TI  - Sampling of wide local excision specimens in cutaneous malignant melanoma.
AB  - BACKGROUND: Wide local excisions (WLEs) are frequently undertaken in the
      management of cutaneous melanoma; however, there is a considerable variability in
      their macroscopic sampling. The aim of our study was to establish evidence-based
      guidelines for the macroscopic handling of these specimens with a subsequent
      review of the impact on our service. METHODS: The study group of 128 cases with
      initial biopsy and subsequent WLE in our institution in 2010 were identified by a
      computer-generated search. From analysis of this group, guidelines for
      macroscopic sampling were derived with a repeat search performed in 2012.
      RESULTS: Residual melanoma was detected only in those cases in which the original
      specimen had clear margins of <=1 mm or with a pigmented lesion. A 32% increase
      in case numbers was noted over this period with a reduction of 6.2% in block
      numbers. Average block numbers per case were reduced by 2.3 (30.7%). CONCLUSIONS:
      We have shown that for WLE specimens with no evidence of a macroscopic lesion and
      clear margins on original biopsy, little is to be gained from extensive sampling.
      In these cases we recommend a maximum of 3 blocks per case. Reduction in sampling
      based on this evidence would result in saving valuable laboratory resources.

PMID- 29168593
TI  - Respiratory regulation by steroids in newborn rats: a sex-specific balance
      between allopregnanolone and progesterone receptors.
AB  - NEW FINDINGS: What is the central question of this study? What are the
      contributions of allopregnanolone, the neuroactive metabolite of progesterone,
      and nuclear (nPR) and membrane (mPR) progesterone receptors to the respiratory
      effect of progesterone in newborn rats? What is the main finding and its
      importance? Acute progesterone injection increases the apnoea frequency, whereas
      finasteride (which blocks the conversion of progesterone to allopregnanolone)
      reduces apnoea frequency. An nPR agonist decreases apnoea frequency in males and
      an mPR agonist decreases apnoea frequency in males and females. Chronic injection
      of progesterone decreases the frequency of apnoea more efficiently in males than
      in females. We tested the hypothesis that the effects of progesterone on apnoea
      frequency in newborn rats are the result of a balance between its neuroactive
      metabolite, allopregnanolone (GABAA receptor modulator), and progesterone
      receptors. We used male and female rats between 10 and 12 days of age and
      recorded respiratory and metabolic parameters (whole-body plethysmography), and
      assessed the frequency and duration of apnoeas in normoxia. We tested the effects
      of a single injection of progesterone (4 mg kg-1 , i.p.), finasteride (10 mg kg-1
      , i.p.; a 5alpha-reductase antagonist, which blocks the conversion of
      progesterone to allopregnanolone), finasteride plus progesterone, or agonists of
      the nuclear or membrane progesterone receptors (R5020 or Org-od-02-0, 4 mg kg-1
      ). To test the hypothesis that chronic exposure to progesterone reduces the
      frequency of apnoeas, we used male and female rats treated daily with
      progesterone between postnatal days 3 and 12. The acute injection of progesterone
      reduced minute ventilation and metabolic rate and increased the frequency of
      apnoeas. Finasteride decreased the frequency of apnoeas, and finasteride plus
      progesterone did not increase apnoea frequency but decreased minute ventilation
      in female rats. Although R5020 decreased apnoea frequency only in males, Org-od
      02-0 decreased apnoea frequency in males and females and decreased respiratory
      frequency in females. Chronic progesterone treatment reduced apnoea frequency
      more efficiently in males than in females, but in females (not in males) an acute
      injection of caffeine (the gold standard for the treatment of apnoea in preterm
      neonates) further reduced apnoea frequency. Apnoea frequency in newborn rats is,
      in part, determined by a sex-specific balance between allopregnanolone, GABAA
      receptors and progesterone receptors.

PMID- 29168592
TI  - Bronsted Acid-Catalyzed Tandem Cyclizations of Tryptamine-Ynamides Yielding 1H
      Pyrrolo[2,3-d]carbazole Derivatives.
AB  - Ynamides, as versatile synthetic precursors, have attracted much attention from
      synthetic chemists and sparked the development of a number of methodologies for
      the construction of various structures. 1H-Pyrrolo[2,3-d]carbazole is a core
      scaffold of a series of monoterpene indole alkaloids found in Kopsia, Strychnos,
      and Aspidosperma, for example. In this study, 1H-pyrrolo[2,3-d]carbazole
      derivatives were synthesized by a Bronsted acid-catalyzed tandem cyclization
      starting from tryptamine-based ynamides. This strategy prevented Wagner-Meerwein
      rearrangement by instantaneous intramolecular nucleophilic trapping of the
      indoleninium to afford a tetracyclic indoline via an in situ-formed enol species
      induced by the formation of a more stable conjugate diene moiety. The functional
      group tolerances were investigated by using a series of readily available
      substrates. A plausible mechanism has been proposed based on the evidence of the
      capture of the hemiaminal intermediate. Lastly, a Buchi ketone, which is the
      pivotal intermediate in the synthesis of the indole alkaloid vindorosine, was
      synthesized by utilizing our newly developed methodology.

PMID- 29168595
TI  - Berberine impairs embryonic development in vitro and in vivo through oxidative
      stress-mediated apoptotic processes.
AB  - Berberine, an isoquinoline alkaloid isolated from several traditional Chinese
      herbal medicines, has been shown to suppress growth and induce apoptosis in some
      tumor cell lines. However, berberine has also been reported to attenuate H2 O2 
      induced oxidative injury and apoptosis. The basis for these ambiguous effects of
      berberine-triggering or preventing apoptosis-has not been well characterized to
      date. In the current investigation, we examined whether berberine exerts
      cytotoxic effects on mouse embryos at the blastocyst stage and affects subsequent
      embryonic development in vitro and in vivo. Treatment of blastocysts with
      berberine (2.5-10 MUM) induced a significant increase in apoptosis and a
      corresponding decrease in trophectoderm cell number. Moreover, the implantation
      success rate of blastocysts pretreated with berberine was lower than that of
      their control counterparts. Pretreatment with berberine was also associated with
      increased resorption of postimplantation embryos and decreased fetal weight. In
      an animal model, intravenous injection of berberine (2, 4, or 6 mg/kg body
      weight/d) for 4 days resulted in apoptosis of blastocyst cells and early
      embryonic developmental injury. Berberine-induced injury of mouse blastocysts
      appeared to be attributable to oxidative stress-triggered intrinsic apoptotic
      signaling processes that impaired preimplantation and postimplantation embryonic
      development. Taken together, our results clearly demonstrate that berberine
      induces apoptosis and retards early preimplantation and postimplantation
      development of mouse embryos, both in vitro and in vivo.

PMID- 29168594
TI  - A longitudinal communication approach in advanced lung cancer: A qualitative
      study of patients', relatives' and staff's perspectives.
AB  - Communication and the care of patients with advanced cancer are a dynamic,
      interactive and challenging process, often characterised in every day practice by
      discontinuity and lack of coordination. The objective of this study was to
      explore the patients' and family-caregivers' needs and preferences regarding
      communication, quality of life and care over the trajectory of disease. The
      second aim was to assess health professionals' views on a longitudinally
      structured, forward-thinking communication approach based on defined milestones.
      A qualitative approach was chosen incorporating semi-structured interviews with
      nine patients with metastatic lung cancer and nine relatives, and focus groups
      with 15 healthcare providers from different professions involved in the care of
      these patients. Patients and relatives described a situation of shock and coping
      deficits with moments of insufficient communication and lack of continuity in
      care. Healthcare providers reported the strong need for improvement in
      communication within the team and between patients and professionals and welcomed
      the implementation of a longitudinal communication approach. Requirements for the
      implementation of a longitudinal communication approach include specific
      communication training with focus on the process that patients and relatives are
      involved in. Team-building measures and the necessary flexibility to respect
      individuality in life should be incorporated.

PMID- 29168596
TI  - DNA replication stress and cancer chemotherapy.
AB  - DNA replication is one of the fundamental biological processes in which
      dysregulation can cause genome instability. This instability is one of the
      hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous
      experimental and clinical studies have indicated that most tumors have
      experienced and overcome the stresses caused by the perturbation of DNA
      replication, which is also referred to as DNA replication stress (DRS). When we
      consider therapeutic approaches for tumors, it is important to exploit the
      differences in DRS between tumor and normal cells. In this review, we introduce
      the current understanding of DRS in tumors and discuss the underlying mechanism
      of cancer therapy from the aspect of DRS.

PMID- 29168597
TI  - Reliability and clinical features associated with the IPSG MRI tibiotalar and
      subtalar joint scores in children, adolescents and young adults with haemophilia.
AB  - OBJECTIVES: To assess the reliability of the IPSG MRI scale for tibiotalar (TTJ)
      and subtalar joint (STJ) changes in young haemophilic patients, correlating MRI
      findings with functional scores and 3D-rearfoot kinematics. METHODS: A total of
      37 haemophilic patients underwent bilateral MRI of the footankle, clinical
      evaluation and quantitative assessment of their 3D-rearfoot kinematics during
      walking. TTJ and STJ soft tissues were assessed twice along with osteochondral
      changes by two radiologists using the IPSG MRI scale. Inter- and intra-observer
      reproducibility of MRI scoring were tested by means of kappa statistics.
      Correlational analyses were performed between MRI findings and the Haemophilia
      Joint Health Score 2.1 (HJHS) and 3D-rearfoot kinematic data. RESULTS: The intra
      reader reliability of MRI scoring was good to excellent (Kappa: 0.62-1), whereas
      the inter-reader reliability was moderate to good (Kappa: 0.54-0.79). Weak yet
      significant correlations were found between the frontal plane rearfoot range of
      motion (ROM) during loading response of gait and STJ score, as well as between
      frontal plane rearfoot ROM during the terminal stance phase and the rearfoot
      osteochondral lesions. CONCLUSION: The IPSG score appears applicable to not only
      the TTJ but also the STJ. Contrary to TTJ lesions, those of the STJ do not
      correlate with the HJHS but do with 3D-rearfoot kinematic data.

PMID- 29168598
TI  - PRIMA-1 induces p53-mediated apoptosis by upregulating Noxa in esophageal
      squamous cell carcinoma with TP53 missense mutation.
AB  - TP53 is associated with the resistance of cytotoxic treatment and patient
      prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma
      (ESCC) is extraordinarily high, at over 90%. PRIMA-1 (p53 re-activation and
      induction of massive apoptosis) has recently been reported to restore the
      function of mutant TP53; however, its antitumor effect and mechanism in ESCC
      remain unclear. After evaluating the TP53 mutation status of a panel of 11 ESCC
      cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA-1
      administration on cells with different TP53 status by conducting cell viability
      and apoptosis assays. The expression levels of proteins in p53-related pathways
      were examined by Western blotting, while knockdown studies were conducted to
      investigate the mechanism underlying PRIMA-1's function. An ESCC xenograft model
      was further used to evaluate the therapeutic effect of PRIMA-1 in vivo. PRIMA-1
      markedly inhibited cell growth and induced apoptosis by upregulating Noxa
      expression in ESCC cell lines with TP53 missense mutations, whereas no apoptosis
      was induced in ESCC with wild-type TP53 and TP53 with frameshift and nonsense
      mutations. Importantly, the knockdown of Noxa canceled the apoptosis induced by
      PRIMA treatment in ESCC cell lines with TP53 missense mutations. PRIMA-1
      administration, compared with placebo, showed a significant antitumor effect by
      inducing Noxa in the xenograft model of an ESCC cell line with a TP53 missense
      mutation. PRIMA-1 exhibits a significant antitumor effect, inducing massive
      apoptosis through the upregulation of Noxa in ESCC with TP53 missense mutations.

PMID- 29168600
TI  - Molecular characterization of Helicobacter pylori resistance to rifamycins.
AB  - INTRODUCTION: Antibiotic resistance is a major contributing factor in treatment
      failure of Helicobacter pylori eradication. Rifabutin (RB) is a rescue treatment
      and rifampicin (RP) is used to screen RB resistance in vitro. The aim of this
      study was to evaluate the rate of rifamycins resistance and to determine the
      mutations in the rpoB gene conferring resistance to discuss the current break
      point. METHODS: Antimicrobial susceptibility to RP was first determined by E-test
      for 1015 H. pylori isolates. RP and RB MICs were then determined by agar dilution
      method for strains with MIC of RP > 1 mg/L, and the rpoB gene was sequenced.
      RESULTS: Overall, 54 of 1015 strains exhibited a RP MIC > 1 mg/L by agar dilution
      method. Among these 54 strains, 10 had MICs of RP > 4 mg/L and RB >= 1 mg/L. They
      all carried at least one mutation in the rpoB gene at codons 530, 538, 540, 525
      in the RP resistance-determining region (RRDR). Implication of the mutation L547F
      was confirmed by site-directed mutagenesis experiment. In contrast, among the 44
      H. pylori isolates with a MIC of RP comprised between 2 and 4 mg/L, only 4 of 44
      (9%) strains exhibited a mutation in rpoB, but outside RRDR (codons 470, 499,
      636, or 657). For 31 of 44 tested strains, the RB MICs were <=0.064 mg/L.
      CONCLUSION: These results suggest that H. pylori isolates should be classified as
      resistant to RP for MICs > 4 mg/L. We considered that the optimal cut off for RB
      was >=0.125 mg/L. We report a new mutation responsible for rifamycins,
      resistance, L547F.

PMID- 29168599
TI  - HOXC13 promotes proliferation of esophageal squamous cell carcinoma via
      repressing transcription of CASP3.
AB  - Esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal
      cancer, is one of the most common digestive tumors worldwide. In this study, we
      confirmed that HOXC13, a member of the homeobox HOXC gene family, was
      significantly upregulated in ESCC and its overexpression was associated with
      poorer clinical characteristics and worse prognosis. Moreover, knockdown of
      HOXC13 inhibited proliferation and induced apoptosis of ESCC through upregulating
      CASP3. ChIP analysis revealed that HOXC13 repressed transcription of CASP3
      through directly targeting the promotor region of CASP3. We also found that miR
      503 downregulated HOXC13, by directly targeting its 3'UTR, and inhibited
      proliferation of ESCC. In conclusion, our study demonstrates that HOXC13, which
      is directly targeted by miR-503, promotes proliferation and inhibits apoptosis of
      ESCC through repressing transcription of CASP3.

PMID- 29168601
TI  - Tissue is the issue to confirm benign disease at pleuroscopy in lung cancer.

PMID- 29168602
TI  - Proliferation genes in lung development associated with the prognosis of lung
      adenocarcinoma but not squamous cell carcinoma.
AB  - There are many similarities between embryonic development and tumorigenesis, and
      gene expression profiles show that certain correlations exist between the gene
      signature during development and the clinical phenotypes of different cancers.
      Our group previously reported the gene expression profiles of human lung
      development, and the expression of one group of proliferation-related genes (PTN1
      genes) steadily decreased during lung development. Here, we examined the
      prognostic value of PTN1 genes in 5 independent lung adenocarcinoma (ADC) and 5
      lung independent squamous cell carcinoma (SCC) microarray datasets and found that
      the expression levels of PTN1 genes were associated with survival in lung ADC but
      not lung SCC. All of the lung ADC datasets contained a set of highly correlated
      genes from PTN1 genes, but the lung SCC datasets had no similar set of genes. We
      identified 63 unique core genes from the PTN1 genes in the 5 lung ADC datasets:
      17 of these core genes appeared in at least 4 of the lung ADC datasets, and the
      17 corresponding proteins clearly interacted more strongly with each other in
      lung ADC than in lung SCC. Moreover, 16 of the 17 core genes play major roles in
      the G2 /M phase of the cell cycle. These data indicate that proliferation-related
      genes in lung development have a significant prognostic value for lung ADC; the
      synergistic effects of the 17 core genes play an important role in lung ADC
      prognosis. These genes may have significant clinical implications for the
      treatment and prognosis of lung ADC.

PMID- 29168604
TI  - More evidence needed for association between sleep practices and stillbirth.

PMID- 29168603
TI  - Eye gaze perception in bipolar disorder: Self-referential bias but intact
      perceptual sensitivity.
AB  - OBJECTIVES: Deficits in social cognition predict poor functional outcome in
      severe mental illnesses such as schizophrenia and autism. However, research
      findings on social cognition in bipolar disorder (BD) are sparse and
      inconsistent. This study aimed to characterize a critical social cognitive
      process-eye gaze perception-and examine its functional correlates in BD to inform
      psychopathological mechanisms. METHODS: Thirty participants with BD, 37 healthy
      controls (HC), and 46 psychiatric controls with schizophrenia (SZ) completed an
      eye-contact perception task. They viewed faces with varying gaze directions, head
      orientations, and emotion, and made eye-contact judgments. Psychophysics methods
      were used to estimate perception thresholds and the slope of the perception
      curve, which were then compared between the groups and correlated with clinical
      and functional measures using Bayesian inference. RESULTS: Compared with HC,
      patients with BD over-perceived eye contact when gaze direction was ambiguous,
      and this self-referential bias was similar to that in SZ. Patients with BD had
      lower thresholds (i.e., needed weaker eye-contact signal to start perceiving gaze
      as self-directed) but a similar slope compared with HC. Regression analyses
      showed that steeper slope predicted better socio-emotional functioning in HC and
      SZ, but not in BD. CONCLUSIONS: The psychopathology of social dysfunction was
      fundamentally different between BD and SZ in this modest sample. Eye gaze
      perception in BD was characterized by a self-referential bias but preserved
      perceptual sensitivity, the latter of which distinguished BD from SZ. The
      relationship between gaze perception and broader socio-emotional functioning in
      SZ and HC was absent in BD.

PMID- 29168605
TI  - What psychologists need to know about psychotropic medications.
AB  - Despite the fact that today most of the patients with psychological disturbances
      assume some form of psychotropic drug treatment, clinical psychologists may have
      little familiarity with psychopharmacology and are substantially unaware of
      subtle and yet pervasive potential effects of medications in clinical
      presentations. In their training, psychologists are generally exposed, at best,
      to some general principles of drug action. Standard psychopharmacology textbooks
      tend to omit the subtle psychological changes that may occur during psychotropic
      drug treatment. Clinical pharmacopsychology consists of the application of
      clinical psychology to the full understanding of pharmacological effects. The
      domains of clinical pharmacopsychology encompass the clinical benefits of
      psychotropic drugs, the characteristics that predict responsiveness to treatment,
      the vulnerabilities induced by treatment (side effects, behavioural toxicity,
      iatrogenic comorbidity), and the interactions between drug treatment and
      psychological variables. The DSM-5 refers to a patient population that no longer
      exists: subjects who display various manifestations of psychological distress who
      do not receive any form of drug treatment for it. Any type of psychotropic drug
      treatment, particularly after long-term use, may increase the risk of
      experiencing additional psychopathological problems that do not necessarily
      subside with discontinuation of the drug. The changes may be persistent and not
      limited to a short phase, such as in the case of withdrawal reactions, and cannot
      be subsumed under the generic rubrics of adverse events or side effects.

PMID- 29168608
TI  - Bilateral Awards from European Chemical Societies.

PMID- 29168606
TI  - Role of seed size, phenology, oogenesis and host distribution in the specificity
      and genetic structure of seed weevils (Curculio spp.) in mixed forests.
AB  - Synchrony between seed growth and oogenesis is suggested to largely shape trophic
      breadth of seed-feeding insects and ultimately to contribute to their co
      existence by means of resource partitioning or in the time when infestation
      occurs. Here we investigated: (i) the role of seed phenology and sexual
      maturation of females in the host specificity of seed-feeding weevils (Curculio
      spp.) predating in hazel and oak mixed forests; and (ii) the consequences that
      trophic breadth and host distribution have in the genetic structure of the weevil
      populations. DNA analyses were used to establish unequivocally host specificity
      and to determine the population genetic structure. We identified 4 species with
      different specificity, namely Curculio nucum females matured earlier and infested
      a unique host (hazelnuts, Corylus avellana) while 3 species (Curculio venosus,
      Curculio glandium and Curculio elephas) predated upon the acorns of the 2 oaks
      (Quercus ilex and Quercus pubescens). The high specificity of C. nucum coupled
      with a more discontinuous distribution of hazel trees resulted in a significant
      genetic structure among sites. In addition, the presence of an excess of local
      rare haplotypes indicated that C. nucum populations went through genetic
      expansion after recent bottlenecks. Conversely, these effects were not observed
      in the more generalist Curculio glandium predating upon oaks. Ultimately, co
      existence of weevil species in this multi-host-parasite system is influenced by
      both resource and time partitioning. To what extent the restriction in gene flow
      among C. nucum populations may have negative consequences for their persistence
      in a time of increasing disturbances (e.g. drought in Mediterranean areas)
      deserves further research.

PMID- 29168607
TI  - The relationship between perceived organisational threat and compassion for
      others: Implications for the NHS.
AB  - The National Health Service (NHS) is known to be a challenging place to work,
      with financial and performance targets placing increasing pressure on the
      organisation. This study aimed to investigate whether these pressures and threats
      might be detrimental to the quality of care and the compassion that the NHS
      strives to deliver. Quantitative data were collected via self-report
      questionnaires from healthcare professionals across 3 NHS trusts in England in
      order to measure Self-compassion; Compassion for Others; Perceived Organisational
      Threat; and Perceived Organisational Compassion. Qualitative data were also
      collected to explore the threats considered most pertinent to healthcare
      professionals at present. The key findings suggest that an increase in Perceived
      Organisational Threat may reduce an individual's ability to give compassion to
      others; however, Self-compassion and Perceived Organisational Compassion were
      better predictors of Compassion for Others. This highlights the need to consider
      compassion at a systemic level, providing interventions and training not only to
      cultivate self-compassion in healthcare professionals, but also to encourage
      compassion across the NHS more generally. In promoting self-compassion and
      increasing the level of compassion that employees feel they receive at work,
      healthcare professionals may be better able to maintain or improve their level of
      compassion for service users and colleagues.

PMID- 29168609
TI  - The increasing maturity of the von Willebrand factor collagen binding in von
      Willebrand disease diagnosis.

PMID- 29168610
TI  - Rural placement experiences in dental education and the impact on professional
      intentions and employment outcomes-A systematic review.
AB  - CONTEXT/INTRODUCTION: The availability of clinical dental services in rural
      locations is a major concern for many countries as dental care professionals
      gravitate to work in metropolitan areas. This systematic review examines the
      literature on Rural Placement Programs within dentistry and their impact on
      workforce intentions and employment outcomes. The review provides a detailed
      analysis of the methodological characteristics of the literature, considers the
      quality of the evidence and compares the outcomes within an international
      context. MATERIALS AND METHODS: The systematic review identified published
      literature between 2005 and 2016 from databases including EMBASE, MEDLINE,
      PubMed, NursingOVID and Cochrane. The PRISMA protocol was adopted for the
      development of the study, and the Health Gains Notation Framework was implemented
      to assess the quality of the selected research papers. RESULTS: Eleven studies
      considering Rural Clinical Placement Programs met the inclusion criteria. The
      studies were from Australia, South Africa, United States, Thailand and India. The
      evidence in this review indicates that well-designed, financially supported
      programmes that provide a perceived valuable clinical experience, good
      supervision and professional support in a rural environment can lead to dental
      students stating increased intentions to working in a rural location. However,
      there was a lack of evidence and research into whether these rural intentions
      result in positive action to take up employment in a rural location. CONCLUSION:
      The evidence suggests that well-prepared rural clinical placements, which have
      experienced clinical supervisors, good professional student support from the
      dental school, provide a valuable clinical experience and are sufficiently
      funded, can increase intentions to work in a rural location upon graduation.
      However, there is a lack of evidence in dentistry into whether intentions
      translate into practitioners taking clinical positions in a rural location.
      Future research should be planned, which will undertake longitudinal cohort
      studies to identify factors that have an important influence on rural job choice.

PMID- 29168611
TI  - Predictive Performance of Physiologically Based Pharmacokinetic Models for the
      Effect of Food on Oral Drug Absorption: Current Status.
AB  - A comprehensive search in literature and published US Food and Drug
      Administration reviews was conducted to assess whether physiologically based
      pharmacokinetic (PBPK) modeling could be prospectively used to predict clinical
      food effect on oral drug absorption. Among the 48 resulted food effect
      predictions, ~50% were predicted within 1.25-fold of observed, and 75% within 2
      fold. Dissolution rate and precipitation time were commonly optimized parameters
      when PBPK modeling was not able to capture the food effect. The current work
      presents a knowledgebase for documenting PBPK experience to predict food effect.

PMID- 29168612
TI  - Seed loss before seed predation: experimental evidence of the negative effects of
      leaf feeding insects on acorn production.
AB  - Insect herbivory decreases plant fitness by constraining plant growth, survival
      and reproductive output. Most studies on the effects of herbivory in trees rely
      on correlational inter-individual comparisons and could, thus, be affected by
      confounding factors linked to both herbivory and plant performance. Using the
      Mediterranean Holm oak (Quercus ilex) as a study model, we followed an
      experimental approach in which leaf-feeding insects (mainly Lepidoptera
      caterpillars) were excluded from some shoots in all study trees. Shoots subjected
      to herbivore exclusion exhibited lower defoliation rates and produced more acorns
      than control shoots. Defoliation constrained shoot growth throughout the study
      period, but had no effect on the number of female flowers produced per shoot.
      Acorn production was, however, lower in control shoots due to their higher
      abortion rates, and also to their greater mortality risk during summer drought,
      as shoots with fewer leaves were less likely to survive. Plant reaction to
      herbivory inhibits certain physiological pathways involved in plant growth,
      which, together with the effects of physical damage, reduces the amount and
      efficiency of the photosynthetic tissue. This increases their vulnerability to
      environmental stresses, such as water deficit, which limit resource assimilation.
      Defoliation is likely a key factor affecting oak regeneration, as it may be a
      significant source of seed loss prior to pre-dispersal acorn predation. Further
      experimental studies could help to elucidate its effects in contrasting
      environments. In Mediterranean regions, the harsher droughts predicted by climate
      change models could worsen the effects of insect herbivory on oak reproductive
      output.

PMID- 29168613
TI  - Immune defense of wild-caught Norway rats is characterized by increased levels of
      basal activity but reduced capability to respond to further immune stimulation.
AB  - Studies of wild animals' immunity often use comparison with laboratory-raised
      individuals. Using such an approach, various data were obtained concerning wild
      Norway rat's immunity. Lower or higher potential of immune system cells to
      respond to activation stimuli were shown, because of analysis of disparate
      parameters and/ or small number of analyzed individuals. Inconsistent differences
      between laboratory and wild rats were shown too, owing to great response
      variability in wild rats. We hypothesized that wild rats will express more
      intense immune activity compared to their laboratory counterparts which live in a
      less demanding environment. To test this, we analyzed the circulating levels of
      inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role
      in host immune defense. In addition, we examined the activity of the central
      immune organ, the spleen, including cell proliferation and production of pro
      inflammatory cytokines interferon-gamma (IFN-gamma) and interleukin-17 (IL-17),
      which are major effectors of cellular adaptive immune response. In order to
      obtain reasonable insight into the immunity of wild Norway rats, analysis was
      conducted on a much larger number of individuals compared to other studies.
      Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-gamma
      production concomitantly with lower basal production of anti-inflammatory
      cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild
      compared to laboratory rats. However, lower responsiveness of their spleen cells'
      proinflammatory cytokine production to concanavalin A (ConA) stimulation, along
      with preserved capacity of IL-10 response, might be perceived as an indication of
      wild rats' reduced capability to cope with incoming environmental stimuli, but
      also as a means to limit tissue damage.

PMID- 29168614
TI  - Eastern gray squirrels are consistent shoppers of seed traits: insights from
      discrete choice experiments.
AB  - Seeds of many hardwood trees are dispersed by scatter-hoarding rodents, and this
      process is often mediated by the traits of seeds. Although numerous studies have
      linked seed traits to seed preference by rodents, little is known about how
      rodents forage for seeds when multiple desirable and undesirable seed traits are
      available simultaneously. Here, we adopt a novel method of designing choice
      experiments to study how eastern gray squirrels (Sciurus carolinensis) select for
      6 traits (caloric value, protein content, tannin concentration, kernel mass,
      dormancy period and toughness of shell) among seeds. From n = 426 seed-pair
      presentations, we found that squirrels preferentially consumed seeds with short
      dormancy or tougher shells, and preferentially cached seeds with larger kernel
      mass, tougher shells and higher tannin concentrations. By incorporating random
      effects, we found that squirrels exhibited consistent preferences for seed
      traits, which is likely due to the fitness consequences associated with
      maintaining cached resources. Furthermore, we found that squirrels were willing
      to trade between multiple traits when caching seeds, which likely results in more
      seed species being cached in the fall. Ultimately, our approach allowed us to
      compute the relative values of different seed traits to squirrels, despite
      covariance among studied traits across seed species. In addition, by
      investigating how squirrels trade among different seed traits, important insights
      can be gleaned into behavioral mechanisms underlying seed caching (and, thus,
      seed survival) dynamics as well as evolutionary strategies adopted by plants to
      attract seed dispersers. We describe how discrete choice experiments can be used
      to study resource selection in other ecological systems.

PMID- 29168615
TI  - Impact of rewilding, species introductions and climate change on the structure
      and function of the Yukon boreal forest ecosystem.
AB  - Community and ecosystem changes are happening in the pristine boreal forest
      ecosystem of the Yukon for 2 reasons. First, climate change is affecting the
      abiotic environment (temperature, rainfall and growing season) and driving
      changes in plant productivity and predator-prey interactions. Second,
      simultaneously change is occurring because of mammal species reintroductions and
      rewilding. The key ecological question is the impact these faunal changes will
      have on trophic dynamics. Primary productivity in the boreal forest is increasing
      because of climatic warming, but plant species composition is unlikely to change
      significantly during the next 50-100 years. The 9-10-year population cycle of
      snowshoe hares will persist but could be reduced in amplitude if winter weather
      increases predator hunting efficiency. Small rodents have increased in abundance
      because of increased vegetation growth. Arctic ground squirrels have disappeared
      from the forest because of increased predator hunting efficiency associated with
      shrub growth. Reintroductions have occurred for 2 reasons: human reintroductions
      of large ungulates and natural recolonization of mammals and birds extending
      their geographic ranges. The deliberate rewilding of wood bison (Bison bison) and
      elk (Cervus canadensis) has changed the trophic structure of this boreal
      ecosystem very little. The natural range expansion of mountain lions (Puma
      concolor), mule deer (Odocoileus hemionus) and American marten (Martes americana)
      should have few ecosystem effects. Understanding potential changes will require
      long-term monitoring studies and experiments on a scale we rarely deem possible.
      Ecosystems affected by climate change, species reintroductions and human
      alteration of habitats cannot remain stable and changes will be critically
      dependent on food web interactions.

PMID- 29168616
TI  - Lineage-specific evolution of bitter taste receptor genes in the giant and red
      pandas implies dietary adaptation.
AB  - Taste 2 receptors (TAS2R) mediate bitterness perception in mammals, thus are
      called bitter taste receptors. It is believed that these genes evolved in
      response to species-specific diets. The giant panda (Ailuropoda melanoleuca) and
      red panda (Ailurus fulgens styani) in the order Carnivora are specialized
      herbivores with an almost exclusive bamboo diet (>90% bamboo). Because bamboo is
      full of bitter tasting compounds, we hypothesized that adaptive evolution has
      occurred at TAS2R genes in giant and red pandas throughout the course of their
      dietary shift. Here, we characterized 195 TAS2R genes in 9 Carnivora species and
      examined selective pressures on these genes. We found that both pandas harbor
      more putative functional TAS2R genes than other carnivores, and pseudogenized
      TAS2R genes in the giant panda are different from the red panda. The purifying
      selection on TAS2R1, TAS2R9 and TAS2R38 in the giant panda, and TAS2R62 in the
      red panda, has been strengthened throughout the course of adaptation to bamboo
      diet, while selective constraint on TAS2R4 and TAS2R38 in the red panda is
      relaxed. Remarkably, a few positively selected sites on TAS2R42 have been
      specifically detected in the giant panda. These results suggest an adaptive
      response in both pandas to a dietary shift from carnivory to herbivory, and TAS2R
      genes evolved independently in the 2 pandas. Our findings provide new insight
      into the molecular basis of mammalian sensory evolution and the process of
      adaptation to new ecological niches.

PMID- 29168617
TI  - Carnivore stable carbon isotope niches reflect predator-prey size relationships
      in African savannas.
AB  - Predator-prey size relationships are among the most important patterns underlying
      the structure and function of ecological communities. Indeed, these relationships
      have already been shown to be important for understanding patterns of
      macroevolution and differential extinction in the terrestrial vertebrate fossil
      record. Stable isotope analysis (SIA) is a powerful remote approach to examining
      animal diets and paleodiets. The approach is based on the principle that isotope
      compositions of consumer tissues reflect those of their prey. In systems where
      resource isotope compositions are distributed along a body size gradient, SIA
      could be used to reconstruct predator-prey size relationships. We analyzed stable
      carbon isotope distributions amongst mammalian herbivores in extant and Plio
      Pleistocene African savanna assemblages, and show that the range of delta13 C
      values among mammalian prey species (herbivores and rodents) increases with body
      mass (BM), because C4 plant feeding (essentially grazing) is more common among
      larger taxa. Consequently, delta13 C values of mammalian carnivores in these
      systems are related to species' BM, reflecting a higher average C4 prey component
      in the diets of larger-bodied carnivores. This pattern likely emerges because
      only the largest carnivores in these systems have regular access to the C4 prey
      base, whereas smaller carnivores do not. The delta13 C-BM relationship observed
      in mammalian carnivores is a potentially powerful approach for reconstructing and
      parameterizing predator-prey size relationships in contemporary and fossil
      savanna assemblages, and for interpreting how various behavioral, ecological and
      environmental factors influence prey size selection.

PMID- 29168618
TI  - Nomenclature for factors of the HLA system, update July 2017.

PMID- 29168619
TI  - Gut microbes limit growth in house sparrow nestlings (Passer domesticus) but not
      through limitations in digestive capacity.
AB  - Recent research often lauds the services and beneficial effects of host
      associated microbes on animals. However, hosting these microbes may come at a
      cost. For example, germ-free and antibiotic-treated birds generally grow faster
      than their conventional counterparts. In the wild, juvenile body size is
      correlated with survival, so hosting a microbiota may incur a fitness cost. Avian
      altricial nestlings represent an interesting study system in which to investigate
      these interactions, given that they exhibit the fastest growth rates among
      vertebrates, and growth is limited by their digestive capacity. We investigated
      whether reduction and restructuring of the microbiota by antibiotic treatment
      would: (i) increase growth and food conversion efficiency in nestling house
      sparrows (Passer domesticus); (ii) alter aspects of gut anatomy or function
      (particularly activities of digestive carbohydrases and their regulation in
      response to dietary change); and (iii) whether there were correlations between
      relative abundances of microbial taxa, digestive function and nestling growth.
      Antibiotic treatment significantly increased growth and food conversion
      efficiency in nestlings. Antibiotics did not alter aspects of gut anatomy that we
      considered but depressed intestinal maltase activity. There were no significant
      correlations between abundances of microbial taxa and aspects of host physiology.
      Overall, we conclude that microbial-induced growth limitation in developing birds
      is not driven by interactions with digestive capacity. Rather, decreased
      energetic and material costs of immune function or beneficial effects from
      microbes enriched under antibiotic treatment may underlie these effects.
      Understanding the costs and tradeoffs of hosting gut microbial communities
      represents an avenue of future research.

PMID- 29168620
TI  - Simple Organic Salts Having a Naphthalenediimide (NDI) Core Display
      Multifunctional Properties: Gelation, Anticancer and Semiconducting Properties.
AB  - Following a supramolecular synthon rationale, a dicarboxylic acid derivative
      having a naphthalenediimide (NDI) core, namely, bis-N-carboxymethyl
      naphthalenediimide (NDI-G), was reacted with n-alkyl amines with varying alkyl
      chain lengths to generate a new series of primary ammonium dicarboxylate (PAD)
      salts. The majority of the salts (~85 %) were found to gel various polar
      solvents. The gels were characterized by dynamic rheology and high-resolution
      electron microscopy. Single-crystal and powder X-ray diffraction analyses were
      used to study the supramolecular synthon present in one of the gelator salts
      (i.e., S8). Charge-transfer (CT)-induced gelation with donor molecules such as
      anthracene methanol (Ant) and pyrene (Py) was also possible with S8. The CT
      complex (S8.Ant) displayed anticancer activity as probed by cell migration assay
      on the highly aggresive breast cancer cell line MDA-MB-231. The DMSO gel of
      S8.Ant also displayed semiconducting behavior. To the best of our knowledge,
      simple organic salts with an NDI core that display such mulitifunctional
      properties are hitherto unknown.

PMID- 29168621
TI  - Peripheral muscle training with resistance exercise bands in patients with
      chronic heart failure. Long-term effects on walking distance and quality of life;
      a pilot study.
AB  - AIMS: This study aimed to describe a method of peripheral muscle training with
      resistance bands in patients with chronic heart failure (CHF) and to evaluate its
      effects on the 6 min walk test and quality of life up to 12 months using a home
      based programme. METHODS AND RESULTS: Twenty-two patients with stable CHF (19 men
      and 3 women), mean age 63.2 years (SD 8.1), New York Heart Association class II
      III were randomized to individual home-based training (HT group), or home-based
      training with a group-based start-up in a hospital setting (GT group). A 6 min
      walk test, the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and
      Short Form with 36 items (SF-36) were administered at baseline and after 3, 6, 9,
      and 12 months. Exercise training resulted in statistically significant increased
      walking distance in both groups. The HT group increased on average 107 (80) m
      from baseline to 12 months, and the GT group by 100 (96) m. Health-related
      quality of life, measured with MLHFQ and SF-36, reached statistically significant
      improvements in both groups but at different time points. There were no
      statistically significant differences between groups on any parameters or follow
      ups. CONCLUSIONS: Long-term home-based peripheral muscle training in patients
      with CHF, with or without an introductory period in a hospital setting, can be
      used for initial improvement and retention of walking distance and health-related
      quality of life.

PMID- 29168622
TI  - Mitral valve pressure gradient after percutaneous mitral valve repair: every beat
      counts.
AB  - A patient presented with symptoms of decompensated heart failure 2 months after
      percutaneous mitral valve (MV) repair. Echocardiography demonstrated impaired
      left ventricular function with elevated MV pressure gradients and pulmonary
      pressures during rapid atrial fibrillation. Heart rate control was achieved by
      implantation of a biventricular pacemaker with subsequent His-bundle ablation
      because atrial fibrillation was refractory to medical treatment. During
      biventricular pacing at different rates (50-110 b.p.m.), heart rate correlated
      positively with both MV mean pressure gradient and global longitudinal strain and
      negatively with stroke volume. MV pressure gradients directly translated into
      elevated pulmonary pressures. Thus, rate control and biventricular pacing
      improved cardiac haemodynamics.

PMID- 29168623
TI  - Factors shaping life history traits of two proovigenic parasitoids.
AB  - What shapes the relative investment in reproduction versus survival of organisms
      is among the key questions in life history. Proovigenic insects mature all their
      eggs prior to emergence and are short lived, providing a unique opportunity to
      quantify their lifetime investments in the different functions. We investigated
      the initial eggloads and longevity of 2 proovigenic parasitoid wasps: Anagrus
      erythroneurae and Anagrus daanei, (Hymenoptera: Mymaridae) that develop within
      leafhopper eggs in both agricultural vineyards and natural riparian habitats in
      Northern California. We collected Vitis spp. leaves containing developing
      parasitoids from 3 natural sites (Knight Landing, American River and Putah Creek)
      and 3 agricultural vineyards (Solano Farm, Davis Campus and Village Homes). We
      recorded eggloads at parasitoid emergence and female parasitoid longevity with or
      without honey-feeding. Theory predicts that parasitoids from vineyards (where
      hosts are abundant) would have higher initial eggloads and lower longevity
      compared with parasitoids from riparian habitats (where hosts are scarce).
      Although host density and parasitoid eggloads were, indeed, higher in vineyards
      than in riparian habitats, parasitoid longevity did not follow the predicted
      pattern. Longevity without feeding differed among field sites, but it was not
      affected by habitat type (natural vs agricultural), whereas longevity with
      feeding was not significantly affected by any of the examined factors. Moreover,
      longevity was positively, rather than negatively, correlated with eggloads at the
      individual level, even after correcting for parasitoid body size. The combined
      results suggest a more complex allocation mechanism than initially predicted, and
      the possibility of variation in host quality that is independent of size.

PMID- 29168624
TI  - Comparative studies of critical physiological limits and vulnerability to
      environmental extremes in small ectotherms: how much environmental control is
      needed?
AB  - Researchers and practitioners are increasingly using comparative assessments of
      critical thermal and physiological limits to assess the relative vulnerability of
      ectothermic species to extreme thermal and aridity conditions occurring under
      climate change. In most assessments of vulnerability, critical limits are
      compared across taxa exposed to different environmental and developmental
      conditions. However, many aspects of vulnerability should ideally be compared
      when species are exposed to the same environmental conditions, allowing a
      partitioning of sources of variation such as used in quantitative genetics. This
      is particularly important when assessing the importance of different types of
      plasticity to critical limits, using phylogenetic analyses to test for
      evolutionary constraints, isolating genetic variants that contribute to limits,
      characterizing evolutionary interactions among traits limiting adaptive
      responses, and when assessing the role of cross generation effects. On the other
      hand, vulnerability assessments based on critical thermal/physiological limits
      also need to take place within a context that is relevant to field conditions,
      which is not easily provided under controlled environmental conditions where
      behaviour, microhabitat, stress exposure rates, and other factors will differ
      from field conditions. There are ways of reconciling these requirements, such as
      by taking organisms from controlled environments and then testing their
      performance under field conditions (or vice versa). While comparisons under
      controlled environments are challenging for many taxa, assessments of critical
      thermal limits and vulnerability will always be incomplete unless environmental
      effects within and across generations are considered, and where the ecological
      relevance of assays measuring critical limits can be established. This article is
      protected by copyright. All rights reserved.

PMID- 29168626
TI  - Nomenclature for factors of the HLA system, update September 2017.

PMID- 29168625
TI  - Genetic adaptation as a biological buffer against climate change: potential and
      limitations.
AB  - Climate change profoundly impacts ecosystems and their biota, resulting in range
      shifts, novel interactions, food web alterations, changed intensities of host
      parasite interactions, and extinctions. An increasing number of studies
      documented evolutionary changes in, amongst others, phenology and thermal
      tolerance. In this opinion paper, we argue that, while evolutionary responses
      have the potential to provide a buffer against extinctions or range shifts, a
      number of constraints and complexities blur this simple prediction. First, there
      are limits to evolutionary potential both in terms of genetic variation and
      demographic effects, and these limits differ strongly among taxa and populations.
      Secondly, there can be costs associated with genetic adaptation, such as a
      reduced evolutionary potential towards other (human-induced) environmental
      stressors or direct fitness costs due to trade-offs. Third, the differential
      capacity of taxa to genetically respond to climate change results in novel
      interactions because different organism groups respond to a different degree with
      local compared to regional (cf. dispersal and range shift) responses. These
      complexities result in additional changes in the selection pressures on
      populations. We conclude that evolution can provide an initial buffer against
      climate change for some taxa and populations, but does not guarantee their
      survival. It does not necessarily result in reduced extinction risks across the
      range of taxa in a region or continent. Yet, considering evolution is crucial, as
      it is likely to strongly change how biota will respond to climate change and will
      impact which taxa will be the winners or losers at the local, metacommunity, and
      regional scales. This article is protected by copyright. All rights reserved.

PMID- 29168631
TI  - Mesopore- and Macropore-Dominant Nitrogen-Doped Hierarchically Porous Carbons for
      High-Energy and Ultrafast Supercapacitors in Non-Aqueous Electrolytes.
AB  - Non-aqueous electrolytes (e.g., organic and ionic liquid electrolytes) can
      undergo high working voltage to improve the energy densities of supercapacitors.
      However, the large ion sizes, high viscosities, and low ionic conductivities of
      organic and ionic liquid electrolytes tend to cause the low specific
      capacitances, poor rate, and cycling performance of supercapacitors based on
      conventional micropore-dominant activated carbon electrodes, limiting their
      practical applications. Herein, we propose an effective strategy to
      simultaneously obtain high power and energy densities in non-aqueous electrolytes
      via using a cattle bone-derived porous carbon as an electrode material. Because
      of the unique co-activation of KOH and hydroxyapatite (HA) within the cattle
      bone, nitrogen-doped hierarchically porous carbon (referred to as NHPC-HA/KOH) is
      obtained and possesses a mesopore- and macropore-dominant porosity with an
      ultrahigh specific surface area (2203 m2 g-1) of meso- and macropores. The NHPC
      HA/KOH electrodes exhibit superior performance with specific capacitances of 224
      and 240 F g-1 at 5 A g-1 in 1.0 M TEABF4/AN and neat EMIMBF4 electrolyte,
      respectively. The symmetric supercapacitor using NHPC-HA/KOH electrodes can
      deliver integrated high energy and power properties (48.6 W h kg-1 at 3.13 kW kg
      1 in 1.0 M TEABF4/AN and 75 W h kg-1 at 3.75 kW kg-1 in neat EMIMBF4), as well as
      superior cycling performance (over 89% of the initial capacitance after 10 000
      cycles at 10 A g-1).

PMID- 29168629
TI  - Myostatin and beyond in cirrhosis: all roads lead to sarcopenia.

PMID- 29168632
TI  - Electrostatic Catalysis Induced by Luciferases in the Decomposition of the
      Firefly Dioxetanone and Its Analogue.
AB  - The variations of the barrier heights in the decomposition of the firefly
      dioxetanone and its analogues with the electrostatic field produced by the active
      site amino acid residues in the firefly luciferase are examined by a density
      functional theory study of the high-energy intermediates of the three luciferins.
      The positive electric field along the long-axis direction of the luciferins
      lowers the activation energy and acts as an electrostatic catalyst in the
      thermolysis process. The calculated barrier heights for the firefly dioxetanone
      and its analogues surrounded by the firefly Photinus pyralis luciferase show that
      the energy barrier of the firefly dioxetanone is lowered by the luciferase but is
      raised for the other analogue. Thus, the thermolysis rate is enhanced for the
      natural d-luciferin and reduced for the other analogue by the firefly luciferase,
      which elucidates why the luciferase acts as a catalyst for the natural d
      luciferin but makes some luciferins emit weaker light signals.

PMID- 29168633
TI  - Atomic Sulfur Anchored on Silicene, Phosphorene, and Borophene for Excellent
      Cycle Performance of Li-S Batteries.
AB  - Dissolution of intermediate lithium polysulfides (LiPS) is an inevitable obstacle
      for the solid sulfur-based cathode in Li-S batteries. For the first time, herein,
      atomic sulfur is incorporated into silicene, phosphorene, and borophene to
      intrinsically eliminate the dissolution of LiPS. The small molecular sulfur
      species are anchored on the silicene surface with stronger Si-S interaction than
      the P-S and B-S ones. Meanwhile, a high atomic sulfur coverage (63.1 wt %) is
      achieved in silicene and concomitantly stabilizes the silicene layer. For the S3
      covered silicene, a high theoretical capacity of 857 mA h g-1 is achieved with
      slight dissolution of LiPS originated from the loss of interior S atoms that are
      not directly bound with silicene surface. By realizing the elemental S2 coverage
      on silicene with large surface area, the Li+ ions can react fast with the S2
      species, leading to a high theoretical capacity of 891 mA h g-1 without
      dissolution and migration of the intermediate LiPS. Most interestingly, the
      discharge products of atomic layer of lithium sulfides on silicene surface
      exhibit completely different behaviors from the traditional discharge products of
      solid Li2S, which can function as effective adsorption and activation sites for
      the conversion of LiPS from long chain to short chain by accelerated redox
      reaction. The present study gains some key insights into how the atomic sulfur
      contributes to the intrinsic shuttle inhibition and offers a feasible way to
      design the atomic sulfur-based cathode materials of Li-S batteries with better
      electrochemical performance.

PMID- 29168628
TI  - Casting the net broader to confirm our imaginations: the long road to treating
      wasting disorders.
AB  - Wasting embraces muscle and tissue wasting in sarcopenia and cachexia. This
      article describes recent advances in the field published in the Journal of
      Cachexia, Sarcopenia and Muscle concerning diagnostic tools, biomarker
      development, pathophysiology, and treatment. Studies discussed herein embrace
      those on sarcopenia and cachexia in heart failure, chronic obstructive pulmonary
      disease, and cancer including also animal models.

PMID- 29168634
TI  - Enhanced Performance of Perovskite Solar Cells with Zinc Chloride Additives.
AB  - Perovskite solar cells (PSCs) have attracted extensive attention due to their
      impressive photovoltaic performance. The quality of the perovskite layer is very
      critical to achieve high device performance. Here, we explore the partial
      substitution of PbI2 by ZnCl2 in the preparation of CH3NH3PbI3 and its effects on
      perovskite morphology, optical properties, and photovoltaic performance.
      Consequently, the device with 3% ZnCl2 shows great improvement in power
      conversion efficiency (PCE) from 16.4 to 18.2% compared to that of the control
      device. Moreover, the device is more stable than the control device, with only 7%
      degradation after aging for 30 days. These results are attributed to the
      increased grain size, improved film morphology, and reduced recombination loss
      after the partial substitution of PbI2 by ZnCl2 in the perovskite film. This work
      develops a new approach for morphology control through rational additives in the
      perovskite film, and paves the way toward further enhancing the device
      performances of PSCs including PCE and stability.

PMID- 29168635
TI  - Crystallization Mechanism and Charge Carrier Transport in MAPLE-Deposited
      Conjugated Polymer Thin Films.
AB  - Although spin casting and chemical surface reactions are the most common methods
      used for fabricating functional polymer films onto substrates, they are limited
      with regard to producing films of certain morphological characteristics on
      different wetting and nonwetting substrates. The matrix-assisted pulsed laser
      evaporation (MAPLE) technique offers advantages with regard to producing films of
      different morphologies on different types of substrates. Here, we provide a
      quantitative characterization, using X-ray diffraction and optical methods, to
      elucidate the additive growth mechanism of MAPLE-deposited poly(3-hexylthiophene)
      (P3HT) films on substrates that have undergone different surface treatments,
      enabling them to possess different wettabilities. We show that MAPLE-deposited
      films are composed of crystalline phases, wherein the overall P3HT aggregate size
      and crystallite coherence length increase with deposition time. A complete pole
      figure constructed from X-ray diffraction measurements reveals that in these
      MAPLE-deposited films, there exist two distinct crystallite populations: (i)
      highly oriented crystals that grow from the flat dielectric substrate and (ii)
      misoriented crystals that preferentially grow on top of the existing polymer
      layers. The growth of the highly oriented crystals is highly sensitive to the
      chemistry of the substrate, whereas the effect of substrate chemistry on
      misoriented crystal growth is weaker. The use of a self-assembled monolayer to
      treat the substrate greatly enhances the population and crystallite coherence
      length at the buried interfaces, particularly during the early stage of
      deposition. The evolution of the in-plane carrier mobilities during the course of
      deposition is consistent with the development of highly oriented crystals at the
      buried interface, suggesting that this interface plays a key role toward
      determining carrier transport in organic thin-film transistors.

PMID- 29168637
TI  - Fabrication of Graphene-Polyimide Nanocomposites with Superior Electrical
      Conductivity.
AB  - We report on the fabrication of a novel class of lightweight materials, polyimide
      graphene nanocomposites (0.01-5 vol %), with tunable electrical conductivity. The
      graphene-polyimide nanocomposites exhibit an ultra-low graphene percolation
      threshold of 0.03 vol % and maximum dc conductivity of 0.94 S/cm, which we
      attribute to excellent dispersion, extraordinary electron transport in the well
      dispersed graphene, high number density of graphene nanosheets, and the pi-pi
      interactions between the aromatic moieties of the polyimide and the carbon rings
      in graphene. The dc conductivity data are shown to follow the power-law
      dependence on the graphene volume fraction near the percolation threshold. The ac
      conductivity of the nanocomposites is accurately represented by the extended pair
      approximation model. The exponent s of the approximation is estimated to be 0.45
      0.61, indicating anomalous diffusion of charge particles and a fractal structure
      for the conducting phase, lending support to the percolation model. Low
      temperature dc conductivity of the nanocomposites is well-approximated by the
      thermal fluctuation-induced tunneling. Wide-angle X-ray scattering and
      transmission electron microscopy were utilized to correlate the morphology with
      the electrical conductivity. The lack of maxima in X-ray indicates the loss of
      structural registry and short-range ordering.

PMID- 29168636
TI  - A Synthetic Isoprenoid Lipoquinone, Menaquinone-2, Adopts a Folded Conformation
      in Solution and at a Model Membrane Interface.
AB  - Menaquinones (naphthoquinones, MK) are isoprenoids that play key roles in the
      respiratory electron transport system of some prokaryotes by shuttling electrons
      between membrane-bound protein complexes acting as electron acceptors and donors.
      Menaquinone-2 (MK-2), a truncated MK, was synthesized, and the studies presented
      herein characterize the conformational and chemical properties of the hydrophobic
      MK-2 molecule. Using 2D NMR spectroscopy, we established for the first time that
      MK-2 has a folded conformation defined by the isoprenyl side-chain folding back
      over the napthoquinone in a U-shape, which depends on the specific environmental
      conditions found in different solvents. We used molecular mechanics to illustrate
      conformations found by the NMR experiments. The measured redox potentials of MK-2
      differed in three organic solvents, where MK-2 was most easily reduced in DMSO,
      which may suggest a combination of solvent effect (presumably in part because of
      differences in dielectric constants) and/or conformational differences of MK-2 in
      different organic solvents. Furthermore, MK-2 was found to associate with the
      interface of model membranes represented by Langmuir phospholipid monolayers and
      Aerosol-OT (AOT) reverse micelles. MK-2 adopts a slightly different U-shaped
      conformation within reverse micelles compared to within solution, which is in
      sharp contrast to the extended conformations illustrated in literature for MKs.

PMID- 29168638
TI  - Homology Modeling and Molecular Dynamics Simulation Combined with X-ray Solution
      Scattering Defining Protein Structures of Thromboxane and Prostacyclin Synthases.
AB  - A combination of molecular dynamics (MD) simulations and X-ray scattering (SAXS)
      has emerged as the approach of choice for studying protein structures and
      dynamics in solution. This approach has potential applications for membrane
      proteins that neither are soluble nor form crystals easily. We explore the water
      coupled dynamic structures of thromboxane synthase (TXAS) and prostacyclin
      synthase (PGIS) from scanning HPLC-SAXS measurements combined with MD ensemble
      analyses. Both proteins are heme-containing enzymes in the cytochrome P450
      family, known as prostaglandin H2 (PGH2) isomerase, with counter-functions in
      regulation of platelet aggregation. Currently, the X-ray crystallographic
      structures of PGIS are available, but those for TXAS are not. The use of homology
      modeling of the TXAS structure with ns-MUs explicit water solvation MD
      simulations allows much more accurate estimation of the configuration space with
      loop motion and origin of the protein behaviors in solution. In contrast to the
      stability of the conserved PGIS structure in solution, the pronounced TXAS
      flexibility has been revealed to have unstructured loop regions in connection
      with the characteristic P450 structural elements. The MD-derived and experimental
      solution SAXS results are in excellent agreement. The significant protein
      internal motions, whole-molecule structures, and potential problems with protein
      folding, crystallization, and functionality are examined.

PMID- 29168639
TI  - Towards the centralization of digestive oncologic surgery: changes in activity,
      techniques and outcome.
AB  - The purpose of our letter is to provide some feedback about the article published
      by C Tebe and collaborators*, as it addresses a topic of arduous debate,
      therefore, we feel it is important to put both our opinions and points of view
      forward.

PMID- 29168640
TI  - Underwater hybrid endoscopic submucosal dissection in a rectal polyp: a case
      report of a new application of "underwater endoscopy".
AB  - BACKGROUND: Hybrid endoscopic submucosal dissection (ESD) has been described as
      an alternative to traditional ESD. This technique is less time consuming, but the
      en bloc resection rate is lower than in ESD. Similar to endoscopic mucosal
      resection, the underwater technique could improve preliminary disadvantages of
      hybrid ESD. CASE REPORT: We attempted a mixture resection technique of Hybrid ESD
      with underwater endoscopic mucosal resection (EMR). Using this approach, an
      underwater hybrid ESD was successfully performed without adverse events on a 71
      year old woman with a 20 mm adenoma. The histologic analysis identified a
      tubulovillious adenoma with high grade dysplasia and tumor free margins.
      DISCUSSION: Underwater hybrid ESD could be an alternative to ESD. Moreover the
      modification of the "underwater method" provides a suitable way to overcome the
      technical drawbacks of the hybrid ESD.

PMID- 29168641
TI  - Economic evaluation of endoscopic radiofrequency ablation for the treatment of
      dysplastic Barrett's esophagus in Spain.
AB  - BACKGROUND AND STUDY AIMS: To assess the cost-effectiveness of introducing
      endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal
      resection in selected patients into the standard of care of Barrett's esophagus
      patients with high-grade dysplasia or low-grade dysplasia in Spain. METHODS: The
      disease evolution was modeled via a semi-Markov model. The treatment strategies
      compared included endoscopic treatment based on radiofrequency ablation plus
      endoscopic mucosal resection and the Standard of Care (esophagectomy or
      palliative chemoradiotherapy according to disease status for high-grade dysplasia
      and endoscopic surveillance for low-grade dysplasia). Efficacy rates, transition
      probabilities and utility values were obtained from the literature. Clinical
      management patterns and resource use were modeled according to Spanish clinical
      expert opinion. Costs were expressed in euros (?) from 2016 reflecting the
      Spanish National Health System perspective. Sensitivity analyses were performed
      to assess the robustness of the model. RESULTS: With respect to the Spanish
      Standard of Care, endoscopic treatment based on radiofrequency ablation plus
      endoscopic mucosal resection was a dominant strategy for high-grade dysplasia
      patients. When a willingness-to-pay threshold of ?30,000 per quality-adjusted
      life-years gained was considered, this was cost-effective for low-grade dysplasia
      patients (?12,865 per quality-adjusted life-years gained). The sensitivity
      analyses supported the base case analysis results and pointed towards the main
      drivers of uncertainty in the model. CONCLUSIONS: From a health care decision
      maker, endoscopic treatment based on radiofrequency ablation plus endoscopic
      mucosal resection is the intervention of choice for dysplasic Barrett's esophagus
      patients in Spain.

PMID- 29168642
TI  - A new swallowable intragastric balloon (Elipse(r)). Coffee for everybody? The
      position of GETTEMO.
AB  - Recently, the Elipse(r) swallow balloon with spontaneous evacuation has been
      incorporated. GETTEMO wants to position defending innovations in endoscopic
      treatment of bariatric patients, including this new gastric balloon. Any
      bariatric endoscopic procedure must always be done within a suitable protocol and
      in a Multidisciplinary Unit. In order to ensure maximum safety and to be able to
      effectively solve potential complications, in most of the cases a prior endoscopy
      should be required to rule out complications, the balloon must be implanted (or
      supervised) by a bariatric endoscopist and it is necessary to have an Endoscopic
      Emergency Department.

PMID- 29168643
TI  - Disruptive therapeutic innovation and the opportunity to eliminate a chronic
      disease - The issue of chronic hepatitis C in Spain.
AB  - Public funding decisions must be guided by criteria of scientific evidence, cost
      effectiveness and economic evaluation. As an increase in health-effectiveness
      provided by therapeutic innovations can also substantially raise the cost, the
      cost-effectiveness analysis estimating this increase in the cost per unit of
      health gained compared to the previous technologies should be part of the
      economic evaluation. The measure of effectiveness most frequently used in health
      economic evaluations is the Quality Adjusted Life Year (QALY). Data from a Markov
      analysis presented by Turnes et al. in the last issue of this journal comparing
      two scenarios, pre-DAA and post-DAA in Spain is discussed in this document.

PMID- 29168644
TI  - Hemorrhage and intestinal obstruction secondary to a Meckel's diverticulum: a
      case report.
AB  - We present one case of a 17-year-old male with ten-year history of anemia
      complaining of recurrent bloody stools, abdominal pain and fatigue for 3
      months.The gastroscopy, colonoscopy, the-first-time double-balloon enteroscopy
      (DBE) through the anus and capsule endoscopy were performed with negative
      results. 99mTc-pertechnetate scan showed a round-like high radioactive
      concentration at the ileocecum. Double-balloon enteroscopy through the anus was
      performed again by a more-experienced endoscopic physician, the diverticulum was
      found at a distance of 50 cm to the ileocecal valve. Then a laparotomy was
      performed.

PMID- 29168645
TI  - Esophageal lichen planus: a rare case.
AB  - Lichen planus is a rare, idiopathic disease that usually involves the skin and
      mucosae. Oral lesions occur in two thirds of cases and may occur without skin
      involvement. Esophageal lichen planus occur more frequently in middle-age women,
      it is frequently asymptomatic but may cause odynophagia and dysphagia. Esophageal
      lichen planus has been associated with squamous cell carcinoma. The most
      effective treatment is systemic corticotherapy, but relapse is expected in 85%
      with steroid withdrawal. We present the case of esophageal lichen planus in a 50
      year-old man.

PMID- 29168646
TI  - Anal cytology, histopathology and anoscopy in an anal dysplasia screening
      program: is anal cytology enough?
AB  - BACKGROUND AND AIM: The human papilloma virus is the leading cause of anal
      squamous cell carcinoma. Cytological screening may reduce the associated
      morbidity and mortality. The aim of the study was to estimate the agreement
      between anal cytological examination, histopathology and anoscopic visual
      impression. METHODS: A prospective study of patients who underwent anal dysplasia
      screening between 2011 and 2015, in a proctology clinic of a tertiary referral
      center. RESULTS: During the study period, 141 patients (91% men, 87% with HIV
      infection) underwent 175 anal cytology tests. Of these, 33% were negative for
      intraepithelial lesions or malignancy (NILM), 22% were atypical squamous cells of
      uncertain significance (ASCUS), 33% were low-grade squamous intraepithelial
      lesion (LSIL) and 12% were high-grade squamous intraepithelial lesion (HSIL).
      With regard to anoscopic visual impression, 46% of patients had no lesions and
      excision/biopsy of the identified lesions was performed in the remaining
      patients. The weighted kappa-agreement between abnormal cytological results and
      anoscopic visual impression was moderate (k = 0.48). The weighted kappa-agreement
      between simultaneous anal cytological examinations and anal histopathologic
      findings was low (kappa = 0.20). With regard to the histological examination of
      cases with HSIL or superficially invasive squamous cell carcinoma, 64% of
      patients had dysplasia of a lower grade according to the cytological analysis (6
      ASCUS, 18 LSIL and 4 NILM). CONCLUSION: There was a poor correlation between anal
      cytology, histopathology and anoscopic visual impression and a high number of
      histological studies of HGD that were of a lower dysplastic degree according to
      the cytological examination. Therefore, anal cytology screening should not be
      used as the sole method of anal dysplasia screening.

PMID- 29168647
TI  - Pediatric cardiac care in India: current status and the way forward.

PMID- 29168648
TI  - Pulmonary embolism, mortality, 'weekend effect' and gender: what do we know?

PMID- 29168649
TI  - Utility of molecular tools for extended adjuvant endocrine therapy decisions in
      early breast cancer.

PMID- 29168650
TI  - Statins and cancer survivors: the need for structured guidelines.

PMID- 29168651
TI  - Carvacrol is highly disruptive against coagulase-negative staphylococci in in
      vitro biofilms.
AB  - AIM: To evaluate the antimicrobial activity of carvacrol against stationary-phase
      planktonic and biofilm cells of coagulase-negative staphylococci and comparison
      to traditional antistaphylococcal antibiotics. MATERIALS & METHODS: The
      antimicrobial effect of carvacrol and antibiotics against planktonic and biofilm
      cells were assessed through quantification of the number of culturable and/or
      viable cells. Confocal laser scanning microscopy was used to evaluate the effect
      of carvacrol on the biofilm structure. RESULTS: A concentration of 4 mM of
      carvacrol demonstrated a potent antimicrobial effect, vastly superior than
      ciprofloxacin, rifampicin, gentamicin and vancomycin, both in planktonic and
      biofilm cells. CONCLUSION: Carvacrol is a potential antimicrobial agent, which
      applicability for the prevention and/or treatment of coagulase-negative
      staphylococci biofilm-associated infections is worthwhile investigating in more
      detail.

PMID- 29168652
TI  - Minding the heart: Why are we still not closer to treating depression and anxiety
      in clinical cardiology practice?

PMID- 29168653
TI  - Utilizing biomarkers in colorectal cancer: an interview with Ajay Goel.
AB  - Ajay Goel speaks to Rachel Jenkins, Commissioning Editor. Ajay Goel, PhD, is a
      Professor and Director, Center for Gastrointestinal Research, and Director,
      Center for Translational Genomics and Oncology, at the Baylor Scott & White
      Research Institute, Baylor University Medical Center in Dallas, Texas. Dr Goel
      has spent more than 20 years researching cancer and has been the lead author or
      contributor to over 240 scientific articles published in peer-reviewed
      international journals and several book chapters. He is also a primary inventor
      on more than 15 international patents aimed at developing various biomarkers for
      the diagnosis, prognosis and prediction of gastrointestinal cancers. He is
      currently using advanced genomic and transcriptomic approaches to develop novel
      DNA- and miRNA-based biomarkers for the early detection of colorectal cancers. In
      addition, he is researching the prevention of gastrointestinal cancers using
      integrative and alternative approaches, including botanical products such as
      curcumin (from turmeric) and boswellia. Dr Goel is a member of the American
      Association for Cancer Research (AACR) and the American Gastroenterology
      Association (AGA) and is on the international editorial boards of several
      journals including Gastroenterology, Clinical Cancer Research, Carcinogenesis,
      PLoS ONE, Scientific Reports, Epigenomics, Future Medicine, Alternative Therapies
      in Heath and Medicine and World Journal of Gastroenterology. He is also actively
      involved in peer-reviewing activities for more than 100 international scientific
      journals and various grant review panels of various national and international
      funding organizations. His research has been actively funded by various private
      and federal organizations, including funding from the National Cancer Institute
      (NCI) at the NIH, American Cancer Society (ACS) and other state organizations. He
      has won more than dozen awards and honors, including the Union of European
      Gastroenterology Federation's Distinguished Researcher Award, multiple Poster of
      Distinction Awards from the AGA, and Visiting Professorships from various
      national and international academic institutions and academic bodies. Some of his
      key research interests include: Understanding the basic genetics and epigenetic
      basis of gastrointestinal cancers; Use of epigenetic markers, both DNA and RNA,
      for the early detection of colorectal, pancreatic and other gastrointestinal
      cancers; Personalized medicine and treatment of gastrointestinal cancers;
      Chemoprevention, using complementary and alternative approaches using
      nutraceuticals such as curcumin, green tea, resveratrol and other botanicals.

PMID- 29168654
TI  - Integrating clinicopathologic and genomic tools in chemotherapy decision-making
      for early stage breast cancer.

PMID- 29168655
TI  - Endometrial cancer evolution: new molecular-biologic types and hormonal-metabolic
      shifts.
AB  - The question hidden in the title of this manuscript (whether the topic develops
      or remains constant) is important for all areas of science. It is also a serious
      problem for endometrial cancer (EC) study. In recent times the incidence of EC
      gradually increases in parallel with obesity epidemics. The main point of this
      review was evaluation of changes in EC area in last few decades, which are not
      only seen in tumor incidence, but also in its biology, hormonal-metabolic
      characteristics of patients and in the ratio of risk and anti-risk factors. One
      can hope that data accumulated recently and summarized here under the notion of
      EC evolution will find its use for advancement of EC prevention and treatment.

PMID- 29168656
TI  - Can radiotherapy potentiate the effectiveness of immune checkpoint inhibitors in
      lung cancer?

PMID- 29168658
TI  - The tumor circadian clock: a new target for cancer therapy?

PMID- 29168657
TI  - The hidden pathogenic potential of environmental fungi.
AB  - Invasive fungal infections are a growing threat to immunocompromised patients,
      highlighting the importance of monitoring fungal pathogens. Global warming
      (including climatic oscillations) may select for environmental species that have
      acquired thermotolerance, a key step toward pathogenesis to humans. Also,
      important virulence factors have developed in environmental fungi, because they
      are essential for yeast survival in the environment. Thus, fungi traditionally
      regarded as nonpathogenic to humans have virulence factors similar to those of
      their pathogenic relatives. Here, we highlight the emergence of saprophytic
      environmental fungi - including species of Cryptococcus, Aspergillus,
      Penicillium, Candida and Scedosporium - as new human pathogens. Emerging
      pathogens are, in some cases, resistant to the available antifungals,
      potentiating the threat of novel fungal diseases.

PMID- 29168660
TI  - The interplay between extracellular matrix remodelling and kinase signalling in
      cancer progression and metastasis.
AB  - The extracellular matrix (ECM) is a master regulator of cellular phenotype and
      behaviour. It plays a crucial role in both normal tissue homeostasis and complex
      diseases such as cancer. The interplay between the intrinsic factors of cancer
      cells themselves, including their genotype and signalling networks; and the
      extrinsic factors of the tumour stroma, such as the ECM and ECM remodelling;
      together determine the fate and behaviour of cancer cells. As a consequence,
      tumour progression, metastatic spread and response to therapy are ultimately
      controlled by ECM-driven fine-tuning of intracellular kinase signalling. The
      ability to target and uncouple this interaction presents an emerging and
      promising potential in the treatment of cancer.

PMID- 29168659
TI  - Hydrogel spacers in prostate radiotherapy: a promising approach to decrease
      rectal toxicity.
AB  - High-dose radiation is a well-established method of treatment for prostate
      cancer. The main limiting structure for dose escalation is the rectum. The risk
      of rectal toxicity is related to dose received by the rectum. Several strategies
      for reducing dose to rectum have been explored; these include endorectal balloons
      as well as injection of rectal spacers like hydrogels. They create greater
      distance between rectal wall and prostate to confer a dosimetric advantage to the
      rectum. Early clinical studies with hydrogels have shown favorable outcomes. A
      low incidence of major procedural adverse effects with hydrogel use has been
      reported and it is well tolerated by patients. Hydrogel holds promise in
      establishing itself as an adjunct to standard of care in prostate radiation.

PMID- 29168661
TI  - Spatio-temporal dynamics of cerebral capillary segments with stalling red blood
      cells.
AB  - Optical coherence tomography (OCT) allows label-free imaging of red blood cell
      (RBC) flux within capillaries with high spatio-temporal resolution. In this
      study, we utilized time-series OCT-angiography to demonstrate interruptions in
      capillary RBC flux in mouse brain in vivo. We noticed ~7.5% of ~200 capillaries
      had at least one stall in awake mice with chronic windows during a 9-min
      recording. At any instant, ~0.45% of capillaries were stalled. Average stall
      duration was ~15 s but could last over 1 min. Stalls were more frequent and
      longer lasting in acute window preparations. Further, isoflurane anesthesia in
      chronic preparations caused an increase in the number of stalls. In repeated
      imaging, the same segments had a tendency to stall again over a period of one
      month. In awake animals, functional stimulation decreased the observance of
      stalling events. Stalling segments were located distally, away from the first
      couple of arteriolar-side capillary branches and their average RBC and plasma
      velocities were lower than nonstalling capillaries within the same region. This
      first systematic analysis of capillary RBC stalls in the brain, enabled by rapid
      and continuous volumetric imaging of capillaries with OCT-angiography, will lead
      to future investigations of the potential role of stalling events in cerebral
      pathologies.

PMID- 29168662
TI  - How social stigma sustains the HIV treatment gap for MSM in Mpumalanga, South
      Africa.
AB  - There are gaps in HIV care for men who have sex with men (MSM) in African
      settings, and HIV social stigma plays a significant role in sustaining these
      gaps. We conducted a three-year research project with 49 HIV-positive MSM in two
      districts in Mpumalanga Province, South Africa, to understand the factors that
      inform HIV care seeking behaviors. Semi-structured focus group discussions and
      interviews were conducted in IsiZulu, SiSwati, and some code-switching into
      English, and these were audio-recorded, transcribed, and translated into English.
      We used a constant comparison approach to analyze these data. HIV social stigma
      centered around gossip that sustained self-diagnosis and delayed clinical care
      with decisions to use traditional healers to mitigate the impact of gossip on
      their lives. More collaboration models are needed between traditional healers and
      health professionals to support the global goals for HIV testing and treatment.

PMID- 29168663
TI  - Macro- and micro-heterogeneity of lung endothelial cells: they may not be smooth,
      but they got the moves.

PMID- 29168664
TI  - Pulmonary arterial hypertension and acute respiratory distress syndrome in a
      patient with adult-onset stills disease.
AB  - Adult-onset Still's disease (AOSD) is an inflammatory disorder characterized by
      recurrent fevers, arthralgia, leukocytosis, and a salmon-colored rash. Diagnosis
      is made based on the Yamaguchi criteria. Various cardiac and pulmonary
      manifestations have been described in association with AOSD, including acute
      respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH).
      We describe the first case of both PAH and ARDS in a patient with AOSD who,
      despite aggressive therapy, declined rapidly and ultimately died. There was
      concern for pulmonary veno-occlusive disease given the rate of her
      decompensation, but this was found not to be the case on autopsy. Treatment of
      AOSD with cardiopulmonary involvement requires rapid identification of AOSD
      followed by aggressive immunosuppression.

PMID- 29168665
TI  - The clinicopathological parameters significance of CD133 and Nestin in epithelial
      ovarian cancer: a meta-analysis.
AB  - This meta-analysis was conducted to evaluate the association of CD133 and Nestin
      with epithelial ovarian cancer. Databases (PubMed, EMBASE, Web of Science, China
      National Knowledge Infrastructure, Wanfang) were searched for relevant studies
      updated in August 2017. CD133 and Nestin expression were estimated by
      immunohistochemistry. Statistical analysis was performed by RevMan. A total of 18
      studies were included in this meta-analysis. High expression of both CD133 and
      Nestin was associated with late International Federation of Gynecology and
      Obstetrics stage (p < 0.00001), larger size of residual cancer (p < 0.05). CD133
      overexpression was also associated with higher histological grade (p = 0.0006)
      and lymph node metastases (p < 0.00001). Nestin overexpression was associated
      with a higher rate of treatment resistance (p = 0.0007). Positive expression of
      CD133 and Nestin may be associated with aggressive biological behaviors in
      epithelial ovarian cancer.

PMID- 29168666
TI  - Diagnostic methods used in searching for markers of atrophy in patients with
      multiple sclerosis.
AB  - : The results of available studies on assessment of neurodegenerative lesions in
      multiple sclerosis (MS) patients using different approaches have not been
      conclusive. Currently, clinical assessment is the most commonly used (involving
      primarily mobility assessment), along with magnetic resonance imaging and
      electrophysiological testing. In this review we describe available clinical,
      neuroimaging, electrophysiological and laboratory tests used to assess the
      neurodegeneration in MS. Laboratory markers to determine the risk of disease, its
      conversion and prognosis in MS patients are being constantly sought.
      Cerebrospinal fluid (CSF) sample collection is invasive and constitutes a burden
      to a patient, so serum biomarkers are being investigated. Optimistic preliminary
      results of studies assessing neurofilament light chains (NFL) in serum of MS
      patients, encourage further research. The possibility to use such marker (or a
      group of markers) would significantly facilitate clinical decisions at the stage
      of diagnosis and treatment. Currently used treatments have limited efficacy and
      are associated with numerous adverse effects. Additional information from
      available clinical, imaging, electrophysiological or laboratory biomarker or a
      group of biomarkers, which predict the course and prognosis, will facilitate
      choosing optimal treatment and its escalation at the relevant stage. CONCLUSION:
      Using the diagnostic panel consisting of imaging, neurophysiology and serology
      testing along with clinical and neuropsychological assessment may improve the
      reliability of diagnostic instruments evaluating cerebral atrophy in MS patients.

PMID- 29168668
TI  - The occurrence of fractures after adjuvant treatment of breast cancer: a DBCG
      register study.
AB  - BACKGROUND: Adjuvant treatment in breast cancer patients especially with
      aromatase inhibitors (AIs) has adverse effects on bone metabolism resulting in an
      increased occurrence of fractures. In order to demonstrate this occurrence, long
      term follow-up studies are necessary. From several national registries in
      Denmark, it is possible to link data from different sources and analyze this
      issue. METHODS: A study cohort of 68,842 breast cancer patients prospectively
      diagnosed and registered in the Danish Breast Cancer Cooperative Group's database
      during the period 1995-2012 formed the basis of the analysis. These data were
      matched with data on all types of fractures from the Danish National Patient
      Register and vital data from the Danish Civil Registration System. RESULTS: After
      data cleaning 66,502 patients were available for analysis and 16,360 of these had
      incurred 20,341 fractures with 13,182 patients having just one fracture. These
      fractures were distributed over 214 specific fracture sites. An extended
      multivariable Cox regression model revealed significant association between the
      occurrence of fractures and age, menopause, Charlson comorbidity index (CCI) and
      endocrine therapy such that late menopause and tamoxifen treatment were
      associated with a lower occurrence and AI treatment, age and CCI were associated
      with a higher occurrence of fractures. CONCLUSION: Before advising adjuvant
      therapy with AIs fragile patients with chronic diseases should receive special
      attention in order to reduce the incidence of fractures in this vulnerable group
      of patients.

PMID- 29168669
TI  - Awake craniotomy versus craniotomy under general anesthesia for the surgical
      treatment of insular glioma: choices and outcomes.
AB  - OBJECTIVE: To investigate differences in outcomes in patients who underwent
      surgery for insular glioma using an awake craniotomy (AC) vs. a craniotomy under
      general anesthesia (GA). METHODS: Data from patients treated at our hospital
      between 2005 and 2015 were analyzed retrospectively. The preoperative,
      intraoperative, postoperative, and longer term follow-up characteristics and
      outcomes of patients who underwent surgery for primary insular glioma using
      either an AC or GA were compared. RESULTS: Of the 52 identified patients, 24 had
      surgery using an AC and 28 had surgery under GA. The extent of resection was
      similar for the two anesthesia techniques: the median extent of resection was
      61.4% (IQR: 37.8-74.3%) in the WHO grade <4 AC group vs. 50.5% (IQR: 35.0-71.2%)
      in the grade <4 GA group and 73.4% (IQR: 54.8-87.2%) in the grade 4 AC group vs.
      88.6% (IQR: 61.2-93.0%) in the grade 4 GA group. Consistent with literature,
      there were more early neurological deficits after an AC, while the GA group
      showed more new late neurological deficits; however, these trends were not
      significant. Survival was similar between the two groups, with 100% 1- and 2-year
      survival in the grade <4 groups. CONCLUSION: Our results showed that the extent
      of resection, neurological outcomes, and survival were similar using the two
      anesthesia techniques. Since AC is more challenging for the patient and for his
      or her caregiver after surgery, this finding has implications for clinical
      decision-making.

PMID- 29168670
TI  - Influence of the revision of surgical fee schedule on surgeons' productivity in
      Japan: A cohort analysis of 7602 surgical procedures in 2013-2016.
AB  - The goal of this study is to evaluate the pure impact of the revision of surgical
      fee schedule on surgeons' productivity. We collected data from the surgical
      procedures performed by the surgeons working in Teikyo University Hospital from 1
      April through 30 September in 2013-2016. We employed non-radial and non-oriented
      Malmquist model. We defined the decision-making unit as a surgeon with the
      highest academic rank in surgery. Inputs were defined as (1) the number of
      doctors who assisted surgery and (2) the time of surgical operation. The output
      was defined as the surgical fee for each surgery. We focused on the revisions in
      2014 and 2016. We first calculated each surgeon's natural logarithms of the
      changes in productivity, technique and efficiency in 2013-2014, in 2014-2015 and
      in 2015-2016. Then, we subtracted the changes in 2014-2015 from the changes in
      2013-2014 and in 2015-2016. We analyzed 62 surgeons who performed 7602 surgical
      procedures. The productivity changes were not significantly different from 0.
      Their efficiency change was significantly greater than 0, while their technical
      change was smaller than 0 in revision 2014. Their efficiency change was
      significantly smaller than 0, while their technical change was greater than 0 in
      revision 2016 (p < 0.05). This finding suggests that we could increase overall
      productivity through revision if we could increase both efficiency and technique.

PMID- 29168667
TI  - Arterial spin labeling for the measurement of cerebral perfusion and angiography.
AB  - Arterial spin labeling (ASL) is an MRI technique that was first proposed a
      quarter of a century ago. It offers the prospect of non-invasive quantitative
      measurement of cerebral perfusion, making it potentially very useful for research
      and clinical studies, particularly where multiple longitudinal measurements are
      required. However, it has suffered from a number of challenges, including a
      relatively low signal-to-noise ratio, and a confusing number of sequence
      variants, thus hindering its clinical uptake. Recently, however, there has been a
      consensus adoption of an accepted acquisition and analysis framework for ASL, and
      thus a better penetration onto clinical MRI scanners. Here, we review the basic
      concepts in ASL and describe the current state-of-the-art acquisition and
      analysis approaches, and the versatility of the method to perform both
      quantitative cerebral perfusion measurement, along with quantitative cerebral
      angiographic measurement.

PMID- 29168672
TI  - Acute diffusion-weighted imaging lesions in cerebral amyloid angiopathy-related
      convexal subarachnoid hemorrhage.
AB  - Small acute diffusion-weighted imaging (DWI) lesions can accompany intracerebral
      hemorrhage due to cerebral amyloid angiopathy (CAA). We therefore examined the
      occurrence of such lesions in the context of CAA-related convexal subarachnoid
      hemorrhage (cSAH) both in a cross-sectional and longitudinal manner. DWI lesions
      were noted in 14/29 (48%) patients at their index cSAH and 12/21 patients (57%)
      showed acute small DWI lesions at follow-up MRI. Forty-four of 71 (62%) DWI
      lesions were spatially related to areas of cortical superficial siderosis.
      Clarification of the implications of our finding needs the investigation of
      larger patient groups.

PMID- 29168671
TI  - Oral bioavailability enhancement of raloxifene by developing microemulsion using
      D-optimal mixture design: optimization and in-vivo pharmacokinetic study.
AB  - The objective of this work was to utilize a potential of microemulsion for the
      improvement in oral bioavailability of raloxifene hydrochloride, a BCS class-II
      drug with 2% bioavailability. Drug-loaded microemulsion was prepared by water
      titration method using Capmul MCM C8, Tween 20, and Polyethylene glycol 400 as
      oil, surfactant, and co-surfactant respectively. The pseudo-ternary phase diagram
      was constructed between oil and surfactants mixture to obtain appropriate
      components and their concentration ranges that result in large existence area of
      microemulsion. D-optimal mixture design was utilized as a statistical tool for
      optimization of microemulsion considering oil, Smix, and water as independent
      variables with percentage transmittance and globule size as dependent variables.
      The optimized formulation showed 100 +/- 0.1% transmittance and 17.85 +/- 2.78 nm
      globule size which was identically equal with the predicted values of dependent
      variables given by the design expert software. The optimized microemulsion showed
      pronounced enhancement in release rate compared to plain drug suspension
      following diffusion controlled release mechanism by the Higuchi model. The
      formulation showed zeta potential of value -5.88 +/- 1.14 mV that imparts good
      stability to drug loaded microemulsion dispersion. Surface morphology study with
      transmission electron microscope showed discrete spherical nano sized globules
      with smooth surface. In-vivo pharmacokinetic study of optimized microemulsion
      formulation in Wistar rats showed 4.29-fold enhancements in bioavailability.
      Stability study showed adequate results for various parameters checked up to six
      months. These results reveal the potential of microemulsion for significant
      improvement in oral bioavailability of poorly soluble raloxifene hydrochloride.

PMID- 29168673
TI  - The role of dalbavancin in the multi-disciplinary management of wound infections
      in orthopaedic surgery.
AB  - Antimicrobial resistance is continuously increasing among bacterial clinical
      isolates (especially methicillin resistance in Staphylococcus aureus, MRSA),
      negatively impacting on outcomes of patients with Surgical Site Infections
      (SSIs). A multi-disciplinary team work is essential for SSIs prevention and for
      the choice of antibiotic therapy of orthopaedic SSIs. In particular, an
      Antibiotic Stewardship (AS) approach is recommended for preserving the activity
      of old and new antimicrobials. Dalbavancin is a novel antimicrobial agent,
      belonging to the lipoglycopeptides family, recently approved by FDA for the
      treatment of ABSSSIs (Acute Bacterial Skin and Skin Structure Infections) and can
      be considered as a candidate for the treatment of orthopaedic superficial SSIs.
      An antimicrobial activity directed against MRSA and other multi-resistant Gram
      positive pathogens, a bactericidal effect and an extremely extended half-life are
      among key features of this drug. Dalbavancin gives to clinicians the option to
      provide an intravenous antimicrobial agent shown to be as effective as
      conventional therapies, without requiring prolonged admission into the hospital,
      drastically reducing the length of hospital stay (without reducing the treatment
      compliance) and total cost per patient. In this paper, we analyze general,
      microbiological and pharmacological features of dalbavancin, aiming at supporting
      clinicians while positioning this drug in the context of orthopaedic SSIs.

PMID- 29168674
TI  - Breast conserving surgery versus mastectomy: overall and relative survival-a
      population based study by the Danish Breast Cancer Cooperative Group (DBCG).
AB  - BACKGROUND: Observational studies have pointed at a better survival after breast
      conserving surgery (BCS) compared with mastectomy. The aim of the present study
      was to evaluate whether this remains true when more extensive tumor
      characteristics and treatment data were included. METHODS: The cohort included
      patients registered after primary surgery for early invasive breast cancer in the
      database of the Danish Breast Cancer Cooperative Group, in the period 1995-2012.
      The cohort was divided into three groups: (i) patients who primarily had a
      mastectomy, (ii) patients treated by BCS, and (iii) patients who primarily had
      BCS and then mastectomy [intention to treat (ITT) by BCS]. The association
      between overall mortality and standard mortality ratio (SMR) and risk factors was
      analyzed in univariate and multivariate Poisson regression models. RESULTS: A
      total of 58,331 patients were included: 27,143 in the mastectomy group, 26,958 in
      the BCS group, and 4230 in the BCS-ITT group. After adjusting for patient and
      treatment characteristics, the relative risk (RR) was 1.20 (95% CI: 1.15-1.25)
      after mastectomy and 1.08 (95% CI: 1.01-1.15) after BCS first and then
      mastectomy, as compared to BCS. Statistically significant interactions were not
      observed for age, period of treatment, and nodal status, but patients with
      Charlson's Comorbidity Index (CCI) score 2+ had no increased mortality after
      mastectomy, as opposed to patients with CCI 0-1. Loco-regional radiation therapy
      (RT) in node positive patients did not reduce the increased risk associated with
      mastectomy [RR = 1.28 (95% CI 1.19-1.38)]. CONCLUSION: Patients assigned to BCS
      have a better survival than patients assigned to mastectomy. Residual confounding
      after adjustment for registered characteristics presumably explained the
      different outcomes, thus consistent with selection bias. Diversities in RT did
      not appear to explain the observed difference in survival after BCS and
      mastectomy.

PMID- 29168675
TI  - Genome characterization of Turkey Rotavirus G strains from the United States
      identifies potential recombination events with human Rotavirus B strains.
AB  - Rotavirus G (RVG) strains have been detected in a variety of avian species, but
      RVG genomes have been published from only a single pigeon and two chicken
      strains. Two turkey RVG strains were identified and characterized, one in a
      hatchery with no reported health issues and the other in a hatchery with high
      embryo/poult mortality. The two turkey RVG strains shared only an 85.3 %
      nucleotide sequence identity in the VP7 gene while the other genes possessed high
      nucleotide identity among them (96.3-99.9 %). Low nucleotide percentage
      identities (31.6-87.3 %) occurred among the pigeon and chicken RVG strains.
      Interestingly, potential recombination events were detected between our RVG
      strains and a human RVB strain, in the VP6 and NSP3 segments. The epidemiology of
      RVG in avian flocks and the pathogenicity of the two different RVG strains should
      be further investigated to understand the ecology and impact of RVG in commercial
      poultry flocks.

PMID- 29168677
TI  - Social Media Channels in Health Care Research and Rising Ethical Issues.
AB  - Social media channels such as Twitter, Facebook, and LinkedIn have been used as
      tools in health care research, opening new horizons for research on health
      related topics (e.g., the use of mobile social networking in weight loss
      programs). While there have been efforts to develop ethical guidelines for
      internet-related research, researchers still face unresolved ethical challenges.
      This article investigates some of the risks inherent in social media research and
      discusses how researchers should handle challenges related to confidentiality,
      privacy, and consent when social media tools are used in health-related research.

PMID- 29168676
TI  - Molecular and phylogenetic analyses of influenza B viruses isolated from
      pediatric inpatients in South Korea during the 2011-2012 winter season.
AB  - Influenza B virus remains a major cause of respiratory diseases worldwide.
      Because of limited epidemiological and genetic data, the local and global
      transmission patterns of influenza B virus are not fully understood. Here we
      report the molecular and phylogenetic characterization of 163 influenza B virus
      isolates from pediatric inpatients with influenza-like illness in the winter of
      2011-2012 in South Korea. Analysis of haemagglutinin and neuraminidase genes of
      the influenza B isolates revealed that both B/Victoria (62 %) and B/Yamagata
      lineages (38 %) co-circulated during that influenza season, and a considerable
      number of the isolates carried several amino acid substitutions in the four major
      antigenic epitopes of their haemagglutinin protein.

PMID- 29168678
TI  - What Critical Ethical Values Guide Strategic Planning Processes in Health Care
      Organizations?
AB  - This case explores a fictitious hospital's use of co-creation to make a decision
      about redesign of inpatient units as a first step in incorporating stakeholder
      input into creation of governing policies. We apply a "procedural fairness"
      framework to reveal that conditions required for an ethical decision about space
      redesign were not met by using clinician and patient focus groups to obtain
      stakeholder input. In this article, we identify epistemic injustices resulting
      from this process that could undermine confidence in leadership decisions.
      Suggestions are offered for incorporating stakeholder input going forward that
      address prior shortcomings. The result should be conditions that are perceived as
      procedurally fair and decisions that engender confidence in institutional
      leadership.

PMID- 29168679
TI  - What Should Leaders Do When Inefficiency Is Perceived as a Cost of Inclusivity in
      Strategic Planning Processes in Health Care?
AB  - During the development of new health care policies, quality improvement teams can
      face the challenge of weighing differing opinions within the group that can
      hinder progress. It is essential in such cases to refer to the four keys
      principles of quality improvement (QI) as a guide to enhance group cooperation
      and promote development of the mutual objective. Co-production is a model that
      emphasizes the participation of the patient-a service receiver-in the production
      of services being rendered by the health care professional. By putting into
      practice the QI principles and using the model of co-production, quality
      improvement teams can improve efficiency of health systems and clinical outcomes.

PMID- 29168680
TI  - Should Health Care Organizations Use Information Gleaned from Organization
      Sponsored Patient Support Groups in Strategic Planning?
AB  - Online forums and partnerships with patients have several benefits, such as the
      creation of new products and services. However, as with any such initiatives,
      there are risks as well as benefits. Through analysis of a case of misinformation
      being spread through a health care provider-sponsored online support group for
      patients dealing with obesity, this article outlines best practices and
      strategies to deploy in such organization-sponsored patient support groups. These
      strategies would enable organizations and patients to use such forums to the
      fullest extent while preventing or managing their potential risks as best as
      possible.

PMID- 29168681
TI  - Co-Creating an Expansive Health Care Learning System.
AB  - How should practices of co-creation be integrated into health professions
      education? Although co-creation permits a variety of interpretations, we argue
      that realizing a transformative vision of co-creation-one that invites
      professionals to genuinely reconsider the purposes, relationships, norms, and
      priorities of health care systems through new forms of collaborative thought and
      practice-will require radically rethinking existing approaches to professional
      education. The meaningful enactment of co-creative roles and practices requires
      health professionals and students to negotiate competing traditions, pressures,
      and expectations. We therefore suggest that the development of what we call an
      "expansive health care learning system" is crucial for supporting learners in
      meeting the challenges of establishing genuinely co-creative health care systems.

PMID- 29168682
TI  - How Should Organizations Promote Equitable Distribution of Benefits from
      Technological Innovation in Health Care?
AB  - Technological innovations typically benefit those who have good access to and an
      understanding of the underlying technologies. As such, technology-centered health
      care innovations are likely to preferentially benefit users of privileged
      socioeconomic backgrounds. Which policies and strategies should health care
      organizations adopt to promote equitable distribution of the benefits from
      technological innovations? In this essay, we draw on two important concepts-co
      creation (the joint creation of value by multiple parties such as a company and
      its customers) and digitalization (the application of new digital technologies
      and the ensuing changes in sociotechnical structures and relationships)-and
      propose a set of policies and strategies that health care organizations could
      adopt to ensure that benefits from technological innovations are more equitably
      distributed among all target populations, including resource-poor communities and
      individuals.

PMID- 29168683
TI  - Why Aren't Our Digital Solutions Working for Everyone?
AB  - The article explores a digital injustice that is occurring across the country:
      that digital solutions intended to increase health care access and quality often
      neglect those that need them most. It further shows that when it comes to digital
      innovation, health care professionals and technology companies rarely have any
      incentives to focus on underserved populations. Nevertheless, we argue that the
      technologies that are leaving these communities behind are the same ones that can
      best support them. The key is in leveraging these technologies with: (a) design
      features that accommodate various levels of technological proficiency (e
      literacy), (b) tech-enabled community health workers and navigators who can
      function as liaisons between patients and clinicians, and (c) analytics and
      customer relationship management tools that enable health care professionals and
      support networks to provide the right interventions to the right patients.
      Finally, we argue that community health care workers will need to be incentivized
      to play a larger role in building and adopting innovations targeting the
      underserved.

PMID- 29168684
TI  - Using Principles of Co-Production to Improve Patient Care and Enhance Value.
AB  - Unlike goods, which are concrete and easily quantified, services are intangible
      processes that are produced and consumed concurrently. Health care is a service
      that can encourage optimal health outcomes only through meaningful, collaborative
      partnerships between patients and clinicians. Co-production of health services
      can be used as a means to rethink how health care is delivered not only in the
      context of face-to-face encounters in which the benefits of working together are
      obvious, but also in designing systems that can improve patient care and enhance
      value.

PMID- 29168685
TI  - What Are the Professional, Political, and Ethical Challenges of Co-Creating
      Health Care Systems?
AB  - Co-creation is seen by many as a means of meeting the multiple challenges facing
      contemporary health care systems by involving institutions, professionals,
      patients, and stakeholders in new roles, relationships, and collaborative
      practices. While co-creation has the potential to positively transform health
      care systems, it generates a number of political and ethical challenges that
      should not be overlooked. We suggest that those involved in envisioning and
      implementing co-creation initiatives pay close attention to significant questions
      of equity, power, and justice and to the fundamental challenge of securing a
      common vision of the aims of and agendas for health care systems. While such
      initiatives present significant opportunities for improvement, they need to be
      viewed in light of their accompanying professional, political, and ethical
      challenges.

PMID- 29168687
TI  - Healing Hands.
AB  - For the last seven years, my bride of 45 years has been working very hard to
      recover from a series of heart problems and two strokes. In 2015, after hundreds
      of therapies following her 2012 stroke, we were fortunate enough to find a
      therapist who understood the importance of compassion and empathy in clinical
      situations. Within a few months, my wife's physical, cognitive, mental, and
      emotional condition improved profoundly. As a photographer and author, I had been
      documenting her survival, recovery, and flourishing, and I was fortunate enough
      to recognize a moment of beauty and captured a single image that has since become
      my wife's inspiration for living. It is entitled "Healing Hands."

PMID- 29168686
TI  - How Co-Creation Helped Address Hierarchy, Overwhelmed Patients, and Conflicts of
      Interest in Health Care Quality and Safety.
AB  - Co-creation is health professionals' and systems' development of health care
      together with patients and families. Such collaborations yield an exchange of
      values, ideas, and priorities that can individualize care for each patient. Co
      creation has been discussed interchangeably with co-production and shared
      decision making; this article explores co-creation through the lens of quality
      improvement. Although there are barriers to co-creation including physician
      autonomy, patient overwhelm, and conflicts of interest, co-creation has been
      shown to promote patient engagement, peer learning, and improved outcomes.
      Further research is needed in co-creation for systems improvement.

PMID- 29168688
TI  - Long-term treatment with biosimilar epoetin-alpha (HX575) in hemodialysis
      patients with renal anemia: real-world effectiveness and safety in the MONITOR
      CKD5 study?.
AB  - AIMS: To assess real-world effectiveness and safety of intravenous (IV) HX575, a
      biosimilar epoetin-alpha, in hemodialysis (HD) patients. MATERIALS AND METHODS:
      This prospective, observational, pharmacoepidemiological study of adult HD
      patients treated with IV HX575 for renal anemia for up to 24 months was conducted
      in 114 centers in 10 European countries. Of 2,086 enrolled subjects (safety
      sample), 2,023 had >= 1 follow-up visit (effectiveness sample). RESULTS: Most
      (59.3%) patients were male, median age was 68 years. At enrollment, most (82.5%)
      had been treated with an erythropoiesis-stimulating agent, and 73.0% had adequate
      iron stores. At baseline, mean (+/- standard deviation) baseline hemoglobin (Hb)
      was 11.09 (+/- 1.14) g/dL and HX575 dose 106.5 (+/- 78.7) international units
      (IU)/kg/week; at month 24, Hb was 11.25 (+/- 1.19) g/dL and HX575 dose 113.0 (+/-
      102.5) IU/kg/week. Variations in mean HX575 dose and Hb over the study were not
      statistically significant. As to safety, 140 patients (6.7%) experienced >= 1
      adverse event; of these, 19 events (16 patients; 0.8%) were related to HX575
      treatment, 148 (108 patients; 5.2%) were reported as serious, including 12 events
      in 11 patients (0.5%) stated to be related. No cases of anti-epoetin antibodies
      or pure red cell aplasia were reported. CONCLUSIONS: MONITOR-CKD5 confirmed the
      real-world effectiveness and safety profile of IV biosimilar HX575. HD patients
      treated for up to 24 months showed stable dosing patterns and Hb outcomes. The
      safety profile of HX575 is likewise comparable to reference epoetin-alpha.?.

PMID- 29168689
TI  - In-hospital prescriptions of secondary-prevention medications for post-acute
      coronary syndrome patients in South Korea?.
AB  - BACKGROUND: Optimal medical therapy and the management of cardiac risk factors
      are crucial for the secondary prevention of acute coronary syndrome (ACS).
      However, there have been reports on the underutilization of secondary-prevention
      medications for ACS. This study aimed to investigate adherence of in-hospital
      prescriptions to clinical practice guidelines for the secondary prevention of ACS
      using real-world data. MATERIALS AND METHODS: We collected information on ACS
      patients from national insurance claims data. The in-hospital prescriptions of
      secondary-prevention medications for post-ACS patients were analyzed.
      Prescription patterns were analyzed in relation to demographic, clinical, and
      institutional features. The utilization of five recommended medications and the
      factors influencing their use were investigated using logistic regression
      analysis. RESULTS: In total, 1,983 ACS patients were included in this analysis.
      The prescription rates of secondary-prevention medications were 94.4% for
      aspirin, 96.1% for P2Y12 inhibitors, 67.4% for beta-blockers, 63.5% for ACE
      inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and 86.5% for statins.
      Less than half of the patients were prescribed all five recommended medications.
      The prescription rate of secondary-prevention medications was lower in patients
      with unstable angina than in patients with myocardial infarction, particularly
      for beta-blockers and ACEIs/ARBs. The best predictive variable for determining
      the use of all five recommended medications was the type of ACS according to the
      results of the logistic regression analysis. CONCLUSIONS: In Korea, there is room
      for improvement in the prescription rates of secondary-prevention medications in
      post-ACS patients, particularly for beta-blockers and ACEIs/ARBs.?.

PMID- 29168690
TI  - Mitogen-activated protein kinase in gliosis and pilocytic astrocytoma.
AB  - Pilocytic astrocytoma (PA), featuring activation of the mitogen-activated protein
      kinase (MAPK) pathway, is the most common tumor of the pediatric central nervous
      system. However, it remains unknown whether MAPK activation is present in the
      reactive gliosis of non-neoplastic lesions. Therefore, we investigated the
      expression of MAPK in reactive gliosis associated with cavernous angiomas.
      Immunohistochemical expression and the extent of BRAF, ERK, p38, and JNK were
      investigated in 10 patients with gliosis surrounding cavernous angiomas (GS
      group) and 10 patients with PA (PA group). Evaluation of these parameters was
      scored as 0, none; 1, scarce; 2, moderate; 3, global. In the GS group,
      histopathologic features of PA (piloid cells, Rosenthal fibers, microcysts with
      eosinophilic granular bodies) were identified. Expression of ERK, and p38 was
      shown in all patients in the GS and PA group. Expression of BRAF was identified
      in 5 patients (50%) in the GS group and in 8 (80%) in the PA group. The mean
      score of BRAF expression in the PA group was significantly higher than that in
      the GS group (p = 0.019). Reactive gliosis may resemble PA in histological
      findings and MAPK activation. Therefore, PA could be indistinguishable from
      reactive gliosis with classic histopathologic and/or immunohistochemical
      methods.?.

PMID- 29168691
TI  - A recombinant BBSome core complex and how it interacts with ciliary cargo.
AB  - Cilia are small, antenna-like structures on the surface of eukaryotic cells that
      harbor a unique set of sensory proteins, including GPCRs and other membrane
      proteins. The transport of these proteins involves the BBSome, an eight-membered
      protein complex that is recruited to ciliary membranes by the G-protein Arl6.
      BBSome malfunction leads to Bardet-Biedl syndrome, a ciliopathy with severe
      consequences. Short ciliary targeting sequences (CTS) have been identified that
      trigger the transport of ciliary proteins. However, mechanistic studies that
      relate ciliary targeting to BBSome binding are missing. Here we used
      heterologously expressed BBSome subcomplexes to analyze the complex architecture
      and to investigate the binding of GPCRs and other receptors to the BBSome. A
      stable heterohexameric complex was identified that binds to GPCRs with
      interactions that only partially overlap with previously described CTS,
      indicating a more complex recognition than anticipated. Arl6*GTP does not affect
      these interactions, suggesting no direct involvement in cargo loading/unloading.

PMID- 29168692
TI  - Jak2-mediated phosphorylation of Atoh1 is critical for medulloblastoma growth.
AB  - Treatment for medulloblastoma, the most common malignant brain tumor in children,
      remains limited to surgical resection, radiation, and traditional chemotherapy;
      with long-term survival as low as 50-60% for Sonic Hedgehog (Shh)-type
      medulloblastoma. We have shown that the transcription factor Atonal homologue 1
      (Atoh1) is required for Shh-type medulloblastoma development in mice. To
      determine whether reducing either Atoh1 levels or activity in tumors after their
      development is beneficial, we studied Atoh1 dosage and modifications in Shh-type
      medulloblastoma. Heterozygosity of Atoh1 reduced tumor occurrence and prolonged
      survival. We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated
      pathway only in tumor-initiating cells and in human SHH-type medulloblastoma.
      Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1's
      transcriptional activity, and is independent of canonical Jak2 signaling.
      Importantly, inhibition of Jak2 impairs tyrosine 78 phosphorylation and tumor
      growth in vivo. Taken together, inhibiting Jak2-mediated tyrosine 78
      phosphorylation could provide a viable therapy for medulloblastoma.

PMID- 29168695
TI  - Tenofovir disoproxil fumarate as pre-exposure prophylaxis for HIV prevention in
      women with osteoporosis: a case report and review of the literature.
AB  - Pre-exposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF), can
      effectively prevent HIV acquisition. However, TDF can cause changes in bone
      mineral density (BMD). There is little information on the use of PrEP among
      patients with bone disease. We present a case report of a female with pre
      existing osteoporosis who was prescribed PrEP. Over the course of 9 months of
      consistent PrEP use, verified by dried blood spot testing, we report a lack of
      BMD changes on serial dual-emission X-ray absorptiometry scans in this patient.
      This case can inform PrEP care for patients with pre-existing bone disease.

PMID- 29168693
TI  - Zfp281 is essential for mouse epiblast maturation through transcriptional and
      epigenetic control of Nodal signaling.
AB  - Pluripotency is defined by a cell's potential to differentiate into any somatic
      cell type. How pluripotency is transited during embryo implantation, followed by
      cell lineage specification and establishment of the basic body plan, is poorly
      understood. Here we report the transcription factor Zfp281 functions in the exit
      from naive pluripotency occurring coincident with pre-to-post-implantation mouse
      embryonic development. By characterizing Zfp281 mutant phenotypes and identifying
      Zfp281 gene targets and protein partners in developing embryos and cultured
      pluripotent stem cells, we establish critical roles for Zfp281 in activating
      components of the Nodal signaling pathway and lineage-specific genes.
      Mechanistically, Zfp281 cooperates with histone acetylation and methylation
      complexes at target gene enhancers and promoters to exert transcriptional
      activation and repression, as well as epigenetic control of epiblast maturation
      leading up to anterior-posterior axis specification. Our study provides a
      comprehensive molecular model for understanding pluripotent state progressions in
      vivo during mammalian embryonic development.

PMID- 29168696
TI  - Correlation between entecavir penetration in peripheral blood mononuclear cells
      and HBV DNA decay during treatment of HBeAg-negative chronic hepatitis B.
AB  - BACKGROUND: Recently, due to its high effectiveness and tolerability, the
      treatment of chronic hepatitis B with entecavir became a standard practice.
      However, limited knowledge is currently available about its pharmacokinetic
      behaviour and intracellular disposition. Recently, our group reported an inverse
      correlation between entecavir plasma concentrations and the HBV DNA decay at the
      first and third month of treatment, respectively. In this paper we investigated
      the penetration of entecavir in peripheral blood mononuclear cells (PBMC) and in
      plasma, in order to evaluate the relationship between intracellular penetration
      and response, in a cohort of naive patients with hepatitis B e antigen (HBeAg)
      negative CHB. METHODS: Thirty-three patients were prospectively enrolled and gave
      written informed consent: the monitoring of clinical parameters (for example, HBV
      DNA, hepatitis B surface antigen [HBsAg], alanine aminotransferase) was carried
      out at the baseline and then monthly. Entecavir intra-PBMC and plasma trough
      concentrations were measured at 1 month of treatment, through a validated method
      based on liquid chromatography coupled with tandem mass spectrometry. RESULTS:
      While plasma entecavir analysis confirmed previous evidence of inverse
      correlation between drug concentrations and HBV DNA decrease after 3 months of
      treatment (r=-0.723; P<0.001), this correlation was not significant for intra
      PBMC concentrations. When the intracellular disposition ratio (intra-PBMC/plasma
      concentration ratio) was considered, it showed a direct and significant
      correlation with HBV DNA decay at the third month (r=0.485; P=0.004).
      CONCLUSIONS: These results suggest that the antiviral activity of entecavir is
      dependent on its intracellular uptake, thus resulting in lower plasma
      concentrations in patients who have a marked HBV DNA decrease during treatment.

PMID- 29168697
TI  - Direct contact membrane distillation for textile wastewater treatment: a state of
      the art review.
AB  - To meet surging water demands, water reuse is being sought as an alternative to
      traditional water resources. Direct contact membrane distillation (DCMD) has been
      increasingly studied in the past decade for its potential as an emerging cost
      effective wastewater treatment process and subsequent water reuse. This review
      presents a comprehensive overview of the current progress in the application of
      DCMD for textile wastewater treatment based on the available state of the art.
      There are already published review papers about the membrane distillation
      process, but the difference in the present work is that it focuses on the textile
      area, which consumes a lot of water and generates large amounts of wastewater,
      and still needs innovations in the sector. A review focused on the textile sector
      draws the attention of professionals to the problem and, consequently, to a
      solution. Current issues such as the influences of feed solution, membrane
      characteristics and membrane fouling and new insights are discussed. The main
      performance operating conditions and their effects on the separation process are
      given. Likewise, challenges associated with the influence of different dyes on
      the DCMD results are explained. This review also highlights the future research
      directions for DCMD to achieve successful implementation in the textile industry.

PMID- 29168694
TI  - The mechanism of variability in transcription start site selection.
AB  - During transcription initiation, RNA polymerase (RNAP) binds to promoter DNA,
      unwinds promoter DNA to form an RNAP-promoter open complex (RPo) containing a
      single-stranded 'transcription bubble,' and selects a transcription start site
      (TSS). TSS selection occurs at different positions within the promoter region,
      depending on promoter sequence and initiating-substrate concentration.
      Variability in TSS selection has been proposed to involve DNA 'scrunching' and
      'anti-scrunching,' the hallmarks of which are: (i) forward and reverse movement
      of the RNAP leading edge, but not trailing edge, relative to DNA, and (ii)
      expansion and contraction of the transcription bubble. Here, using in vitro and
      in vivo protein-DNA photocrosslinking and single-molecule nanomanipulation, we
      show bacterial TSS selection exhibits both hallmarks of scrunching and anti
      scrunching, and we define energetics of scrunching and anti-scrunching. The
      results establish the mechanism of TSS selection by bacterial RNAP and suggest a
      general mechanism for TSS selection by bacterial, archaeal, and eukaryotic RNAP.

PMID- 29168698
TI  - Abatement of organic pollutants using fly ash based adsorbents.
AB  - The presence of organic pollutants in the environment is of major concern because
      of their toxicity, bio-accumulating tendency, threat to human life and the
      environment. It is a well-known fact that, these pollutants can damage nerves,
      liver, and bones and could also block functional groups of essential enzymes.
      Conventional methods for removing dissolved pollutants include chemical
      precipitation, chemical oxidation or reduction, filtration, ion-exchange,
      electrochemical treatment, application of membrane technology, evaporation
      recovery and biological treatment. Although all the pollutant treatment
      techniques can be employed, they have their inherent advantages and limitations.
      Among all these methods, adsorption process is considered better than other
      methods because of convenience, easy operation and simplicity of design. A
      fundamentally important characteristic of good adsorbents is their high porosity
      and consequent larger surface area with more specific adsorption sites. This
      paper presents a review of adsorption of different pollutants using activated
      carbon prepared from fly ash sources and the attendant environmental
      implications. Also, the ways of overcoming barriers to fly ash utilization
      together with regeneration studies are also discussed.

PMID- 29168699
TI  - Optimization of sulfate removal from wastewater using magnetic multi-walled
      carbon nanotubes by response surface methodology.
AB  - This paper reports a facile method for removal of sulfate from wastewater by
      magnetic multi-walled carbon nanotubes (MMWCNTs). Multi-walled carbon nanotubes
      and MMWCNTs were characterized by X-ray diffraction, Raman, transmission electron
      microscopy, Fourier transform infrared spectroscopy, and vibrating sample
      magnetometry. The results of the analysis indicated that MMWCNTs were synthesized
      successfully. The MMWCNTs can be easily manipulated in a magnetic field for the
      desired separation, leading to the removal of sulfate from wastewater. Response
      surface methodology (RSM) coupled with central composite design was applied to
      evaluate the effects of D/C (adsorbent dosage per initial concentration of
      pollutant (mgadsorbent/(mg/l)initial)) and pH on sulfate removal (%). Using RSM
      methodology, a quadratic polynomial equation was obtained, for removal of
      sulfate, by multiple regression analysis. The optimum combination for maximum
      sulfate removal of 93.28% was pH = 5.96 and D/C = 24.35. The experimental data
      were evaluated by the Langmuir and Freundlich adsorption models. The adsorption
      capacity of sulfate in the studied concentration range was 56.94 (mg/g). It was
      found out that the MMWCNTs could be considered as a promising adsorbent for the
      removal of sulfate from wastewater.

PMID- 29168700
TI  - Photodegradation of some brominated and phenolic micropollutants in raw hospital
      wastewater with CeO2 and TiO2 nanoparticles.
AB  - In this study, the degradations of 2,3,4,5,6-pentabromotoluene (PBT), 2,3,4,5,6
      pentabromoethyl benzene (PBEB), triclosan (TCS) and gemfibrozil (GFZ) in raw
      hospital wastewater were investigated with cerium (IV) oxide and titanium (IV)
      oxide nanoparticles considering the mechanisms of adsorption, photolysis, and
      photocatalysis with UV-C lamps. The effects of nano-CeO2 and nano-TiO2
      concentrations, irradiation times, UV light powers and hospital wastewater pH on
      the photodegradation yields of micropollutants namely PBT, PBEB, TCS and GFZ were
      investigated throughout photocatalysis. The nano-TiO2 produced had an anatase
      phase with crystalline shape with a surface area of 205 m2 g-1 and an average
      size of 11.50 nm. The CeO2 nanoparticles had a spherical shape with a higher
      surface area (302 m2 g-1) than that of TiO2 and a lower average size (8.11 nm).
      It was found that the removals of PBT, PBEB, TCS and GFZ with adsorption (5.7%
      17.1%) and photolysis (9.0%-15.9%) were not significant for both nanoparticles.
      The photodegradation of PBT (92%), PBEB (90%), TCS (97%) and GFZ (95%) with nano
      CeO2 gave better results than nano-TiO2 (90%, 87%, 94% and 93% for PBT, PBEB, TCS
      and GFZ, respectively) under optimum experimental conditions (0.50 g L-1 nano
      CeO2, 45 min irradiation time, 25  degrees C temperature, pH = 8.50, 210 W UV
      light power). Both nanoparticles were reused effectively after photo-removals of
      the micropollutants from the hospital wastewater. The lowest photodegradation
      yields were 80%, 78%, 75% and 74% for TCS, GFZ, PBT and PBEB, respectively, with
      nano-TiO2 after six sequential treatments. The lowest photodegradation yields
      were 86%, 83%, 80% and 79% for the same micropollutants, respectively, with nano
      CeO2 after six sequential treatments. The cost to treat 1 m3 raw hospital
      wastewater were 8.70 ? and 2.28 ?, for the photocatalytic treatments with nano
      TiO2 and nano-CeO2, respectively.

PMID- 29168701
TI  - Wastewater pond systems using chemical precipitation (fellings dams): state of
      the art in Sweden.
AB  - Chemical precipitation in wastewater stabilization ponds - in Scandinavia called
      fellings dams - has been in operation for more than 50 years. Slaked lime and
      aluminium salts are the most common chemicals used for precipitation. Long and
      narrow forms of the ponds and a detention time of at least 5 days have shown,
      even at a low water temperature and below an ice cover, to produce an average
      effluent quality of 70 mg CODCr/l, 0.2 mg Tot-P/l, 20 mg Tot-N/l (CODCr: chemical
      oxygen demand; Tot-P: total phosphorus; Tot-N: total nitrogen) and low levels of
      pathogenic bacteria. The systems use low amounts of energy and no wastewater is
      by-passed at the plants. Fellings dams have recently been tried to support
      overloaded wastewater collection systems.

PMID- 29168702
TI  - The flocculation mechanism and treatment of oily wastewater by flocculation.
AB  - In the present study, the performance of compound flocculants composed of
      different concentrations of polyaluminum chloride (PAC) and cationic
      polyacrylamide (CPAM), the influencing mechanism of the flocculation process and
      the effects of temperature, settling time, and speed and time of stirring were
      investigated. The results show that the poor water quality with high
      concentrations of oil, suspended solids (SS) and polymer greatly increases the
      oily wastewater emulsion stability and the difficulty of the flocculation
      treatment process. The compound flocculant in oily wastewater treatment can
      achieve best results at optimum conditions of temperature 45  degrees C, settling
      time 60 min, and two stirring stages, 250 r.min-1 for 3 min followed by 100 r.min
      1 for 7 min. At the PAC dosage of 80 mg.L-1 and the CPAM dosage of 0.8 mg.L-1,
      the turbidity of oily wastewater is reduced from 153.8 NTU to 11.2 NTU, and the
      turbidity removal rate reaches 92.69%. Through further measurements, oil content
      and SS content are less than 10 mg.L-1, which meets the requirement of the Daqing
      oilfield re-injection standard.

PMID- 29168703
TI  - Use of methyl esterified eggshell membrane for treatment of aqueous solutions
      contaminated with anionic sulfur dye.
AB  - The present study assessed the adsorption of an anionic dye (sulfur blue) by
      methyl-esterified eggshell membrane (MESM), a low-cost and abundant material from
      waste. Adsorption kinetics were investigated using parameters such as pH, contact
      time, initial dye concentration, solution temperature, dosage of adsorbent, and
      particle size of adsorbent. After methyl esterification, the specific surface
      area significantly increased and the negative surface charge of the eggshell
      membrane changed to positive for all pH values, which increased the sulfur dye
      sorption capacity. The optimal conditions for sorption of sulfur dye onto MESM
      resulted in >98% removal and were as follows: <35 MUm particle size, pH 8, 20 min
      contact time and 313 K temperature. In this respect, 0.68-0.73 dry weight mg/L
      sulfur dye was adsorbed per 1 mg/L MESM. The Langmuir adsorption capacity for
      sulfur dye was 187.6 mg/g. In addition, sulfur removal was spontaneous and uptake
      was endothermic. MESM is an inexpensive and effective adsorbent.

PMID- 29168704
TI  - Extracellular polymeric substance production in high rate algal oxidation ponds.
AB  - Integrated algal pond systems (IAPSs) combine anaerobic and aerobic bioprocesses
      to affect sewage treatment. The present work describes the isolation and partial
      characterisation of soluble extracellular polymeric substances (EPSs) associated
      with microalgal bacterial flocs (MaB-flocs) generated in high rate algal
      oxidation ponds (HRAOPs) of an IAPS treating domestic sewage. Productivity and
      change in MaB-flocs concentration, measured as mixed liquor suspended solids
      (MLSS) between morning (MLSSAM) and evening (MLSSPM) were monitored and the
      substructure of the MaB-flocs matrix examined by biochemical analysis and Fourier
      transform infrared spectroscopy (FT-IR). Results show that MaB-flocs from HRAOPs
      are assemblages of microorganisms produced as discrete aggregates as a result of
      microbial EPS production. Formation and accumulation of the EPS was stimulated by
      light. Analysis by FT-IR revealed characteristic carbohydrate enrichment of these
      polymeric substances. In contrast, FT-IR spectra of EPSs from dark-incubated MaB
      flocs confirmed that these polymers contained increased aliphatic and aromatic
      functionalities relative to carbohydrates. These differences, it was concluded,
      were due to dark-induced transition from phototrophic to heterotrophic
      metabolism. The results negate microalgal cell death as a contributor to elevated
      chemical oxygen demand of IAPS treated water.

PMID- 29168705
TI  - Study on COD removal mechanism and reaction kinetics of oilfield wastewater.
AB  - The chemical oxygen demand (COD) removal mechanism and reaction kinetics were
      mainly studied in the treatment of oilfield oily sewage containing polymer by
      three-dimensional electrode reactor. The results proved that the residual active
      oxides O3, H2O2, *OH and active chlorine in the system of electrochemical
      reaction could be effectively detected, and the COD removal mechanism was co
      oxidation of active oxides; Under these experimental conditions: the electrolysis
      current of 6 A, surface/volume ratio of 6/25(cm2.L-1), the reaction time of 50
      min, the CODcr of treated sewage was no more than 50 mg.L-1; the removal reaction
      of COD conformed to apparent second-order reaction kinetic model, the correlation
      coefficient R2 was 0.9728, and the apparent reaction rate constant was k = 3.58 *
      10-4 (L.min-1.mg-1.m-2). To reach the goal, the CODcr was no more than 50 mg.L-1
      in treated sewage, and the theory minimum processing time was 45.73 min. The
      verification of experimental results was consistent with kinetic equations.

PMID- 29168706
TI  - Using terrestrial laser scanning in inventorying of a hybrid constructed wetland
      system.
AB  - The goal of this paper was to evaluate the possibility of using terrestrial laser
      scanning (TLS) for inventorying of a hybrid constructed wetland (CW) wastewater
      treatment plant. The object under study was a turtle-shaped system built in 2015
      in Eastern Poland. Its main purpose is the treatment of wastewater from the
      Museum and Education Centre of Polesie National Park. The study showed that the
      CW system had been built in compliance with the technical documentation, as
      differences between values obtained from the object and those given in the design
      project (max. +/- 20 cm for situation and +/-5 cm for elevation) were within the
      range defined by the legislator. It was also shown that the results were
      sufficiently precise to be used for as-built surveying of the aboveground
      elements of the CW system. The TLS technique can also be employed to analyse
      quantitative changes in object geometry arising during long-term use (e.g.
      landmass slides or erosion), the identification of which can help in selecting
      the hot-spots at risk of damage and thus restore the object to its original state
      as well as prevent new changes.

PMID- 29168707
TI  - Properties of vanadium-loaded iron sorbent after alkali regeneration.
AB  - The aim of this research was to investigate the regeneration and reuse of a
      commercial granular iron sorbent (mainly goethite) when used in vanadium removal.
      A regeneration rate of 3 M NaOH was the highest (85%) achieved, followed by 2 M
      NaOH (79%) and 1 M NaOH (68%). The breakthrough curves show that the regenerated
      material can be reused. The BET (Brunauer-Emmett-Teller) surface area increased
      by 35-38% and the total pore volume increased by 123-130% as a consequence of
      NaOH treatment. The results indicated that sodium hydroxide could be used for the
      regeneration of iron sorbent although the regeneration was incomplete. This may
      be explained by the fact that vanadium diffusion into pores is a significant
      sorption mechanism in addition to complex formation with surface functional
      groups. As a consequence, vanadium desorbability from pores is not as effective
      as the regeneration of surface sites. X-ray photoelectron spectroscopy analyses
      confirmed a very low vanadium content on the surface of the NaOH-treated iron
      sorbent.

PMID- 29168708
TI  - Preparation of magnetic carbon/Fe3O4 supported zero-valent iron composites and
      their application in Pb(II) removal from aqueous solutions.
AB  - Nanoscale zero-valent iron (NZVI) was first assembled on magnetic carbon/Fe3O4
      (CM) with a combination of hydrothermal and liquid phase reduction methods. The
      novel NZVI@CM magnetic nanocomposites have the merits of large surface area,
      unique magnetic property, low cost and environmental friendliness. They can be
      used for Pb(II) removal in aqueous solution. The materials were characterized by
      using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier
      transform-infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA),
      vibrating sample magnetometry (VSM), X-ray photoelectron spectroscopy (XPS) and
      Brunauer-Emmett-Teller (BET) adsorption. The various parameters, such as reaction
      time, dosage of catalyst, solution pH and acid ions concentrations were studied.
      The removal efficiency of Pb(II) can be obviously increased by the combination of
      appropriate CM and NZVI. The removal efficiency of Pb(II) is 99.7% by using 60 mg
      of NZVI@CM at pH 7. The kinetics study indicates that the Pb(II) removal accords
      to pseudo-second-order kinetics model.

PMID- 29168710
TI  - A soil column study to evaluate treatment of trace elements from saline
      industrial wastewater.
AB  - Industrial wastewater from the flue gas desulfurization (FGD) process is
      characterized by the presence of trace elements of concern, such as selenium (Se)
      and boron (B) and relatively high salinity. To simulate treatment that FGD
      wastewater undergoes during transport through soils in subsurface treatment
      systems, a column study (140-d duration) was conducted with native Kansas soil
      and saline FGD wastewater, containing high Se and B concentrations (170 MUg/L Se
      and 5.3 mg/L B) and negligible arsenic (As) concentration (~1.2 MUg/L As). Se, B,
      and As, and dissolved organic carbon concentrations and organic matter
      spectroscopic properties were measured in the influent and outflow. Influent Se
      concentrations were reduced by only ~half in all treatments, and results suggest
      that Se sorption was inhibited by high salinity of the FGD wastewater. By
      contrast, relative concentrations (C/Co) of B in the outflow were typically <10%,
      suggesting that B sequestration may have been enhanced by higher salinity.
      Unexpected elevated As concentrations in the outflow (at >150 MUg/L in the
      treatment with labile organic carbon addition) suggest that soils not previously
      known to be geogenic arsenic sources have the potential to release As to
      groundwater in the presence of high salinity wastewater and under reducing
      conditions.

PMID- 29168709
TI  - Isotopic fractionation of particulate organic matter and its biogeochemical
      implication in the littoral zone of Lake Taihu, China.
AB  - Signatures of stable isotope ratios have previously been used to trace the source
      and transport of particulate organic matter (POM) in freshwater and marine
      ecosystems. In this study, water columns were collected at 22 sites in the
      littoral zone of Lake Taihu in 2014 to investigate the distribution and
      concentration of nutrients and the stable isotope signatures of POM, and their
      potential interrelation. Generally, mean concentration of nitrogen forms (NH4+-N)
      showed substantial variation, probably because they had received large amounts of
      wastewater from various local industrial enterprises. Source analysis by stable
      carbon and nitrogen isotopic ratios showed that the main POM sources were
      phytoplankton. Contrasting correlations were obtained between delta15N and N
      concentrations in effluent river mouths when compared with influent river mouths.
      In effluent river mouths, there was a significant positive correlation between
      delta15N and nitrogen concentration (total nitrogen and ammonia-nitrogen), in
      contrast with the negative correlation in influent river mouths. According to
      these results, more factors should be taken into consideration when stable carbon
      and nitrogen isotopes of POM are used to assess the feeding relationship between
      consumers and prey, as well as the energy flow pathways that support the lake
      pelagic food webs.

PMID- 29168711
TI  - Separation of emulsified crude oil in saline water by flotation with micro- and
      nanobubbles generated by a multiphase pump.
AB  - The flocculation-column flotation with hydraulic loading (HL, >10 m h-1) was
      studied for the treatment of oil-in-water emulsions containing 70-400 mg L-1
      (turbidity = 70-226 NTU) of oil and salinity (30 and 100 g L-1). A polyacrylamide
      (Dismulgan, 20 mg L-1) flocculated the oil droplets, using two floc generator
      reactors, with rapid and slow mixing stages (head loss = 0.9 to 3.5 bar).
      Flotation was conducted in two cells (1.5 and 2.5 m) with microbubbles (MBs, 5-80
      MUm) and nanobubbles (NBs, 50-300 nm diameter, concentration of 108 NBs mL-1).
      Bubbles were formed using a centrifugal multiphase pump, with optimized
      parameters and a needle valve. The results showed higher efficiency with the
      taller column reducing the residual oil content to 4 mg L-1 and turbidity to 7
      NTU. At high HL (27.5 m h-1), the residual oil concentrations were below the
      standard emission (29 mg L-1), reaching 18 mg L-1. The best results were obtained
      with high concentration of NBs (apart from the bigger bubbles). Mechanisms
      involved appear to be attachment and entrapment of the NBs onto and inside the
      flocs. Thus, the aggregates were readily captured, by bigger bubbles (mostly MBs)
      aiding shear withstanding. Advantages are the small footprint of the cells, low
      residence time and high processing rate.

PMID- 29168712
TI  - Adsorption of Congo red dye onto antimicrobial terephthaloyl thiourea cross
      linked chitosan hydrogels.
AB  - Adsorption capacity of three antimicrobial terephthaloyl thiourea cross-linked
      chitosan hydrogels for Congo red dye removal from its aqueous solution has been
      investigated for the first time in this work. These hydrogels were prepared by
      reacting chitosan with various amounts of terephthaloyl diisothiocyanate cross
      linker. The effect of the hydrogel structural variations and several dye
      adsorption processing parameters to achieve the best adsorption capacity were
      investigated. The hydrogels' structural variations were obtained by varying their
      terephthaloyl thiourea moieties content. The processing variables included
      initial concentration of the dye solution, temperature and time of exposure to
      the dye. The adsorption kinetics and isotherms showed that the sorption processes
      were better fitted by the pseudo-second-order equation and the Langmuir equation,
      respectively. On the basis of the Langmuir analysis Congo red dye gave the
      maximum sorption capacity of 44.248 mg/g. The results obtained confirmed that the
      sorption phenomena are most likely to be controlled by chemisorption process. The
      adsorption reaction was endothermic and spontaneous according to the calculated
      results of adsorption thermodynamics.

PMID- 29168714
TI  - Evaluation of nutrient retention in vegetated filter strips using the SWAT model.
AB  - Nutrient fluxes in stream basins need to be controlled to achieve good water
      quality status. In stream basins with intensive agricultural activities,
      nutrients predominantly come from diffuse sources. Therefore, best management
      practices (BMPs) are increasingly implemented to reduce nutrient input to
      streams. The objective of this study is to evaluate the impact of vegetated
      filter strip (VFS) application as an agricultural BMP. For this purpose, SWAT is
      chosen, a semi-distributed water quality assessment model that works at the
      watershed scale, and applied on the Nif stream basin, a small-sized basin in
      Western Turkey. The model is calibrated with an automated procedure against
      measured monthly discharge data. Nutrient loads for each sub-basin are estimated
      considering basin-wide data on chemical fertilizer and manure usage, population
      data for septic tank effluents and information about the land cover. Nutrient
      loads for 19 sub-basins are predicted on an annual basis. Average total nitrogen
      and total phosphorus loads are estimated as 47.85 t/yr and 13.36 t/yr for the
      entire basin. Results show that VFS application in one sub-basin offers limited
      retention of nutrients and that a selection of 20-m filter width is most
      effective from a cost-benefit perspective.

PMID- 29168713
TI  - Recovery of nutrients from digested sludge as struvite with a combination process
      of acid hydrolysis and Donnan dialysis.
AB  - In this study, the effects of the combination of acid hydrolysis and Donnan
      dialysis on the high-quality struvite production from digested sewage sludge were
      examined. The Box-Behnken design was applied in the hydrolysis using oxalic acid
      for the optimization of the conditions that affect the nutrients and metal
      release from digested sludge. An optimal condition was obtained at oxalic acid
      0.5 M, acid/sludge ratio (mL/g) 10/1, and reaction time 60 min. The separation of
      the metals from hydrolyzed sludge liquid was carried out with the Donnan dialysis
      using a Nafion 117 cation exchange membrane. At the end of the 4 hours of
      operating time, the recovery values for Zn, K, Na, Mg, Fe, and Al were obtained
      as 67.9%, 62.1%, 57.6%, 39.4%, 5.3%, and 2.5%, respectively. The produced
      struvite meets the legal limits for fertilizer use in terms of Cd, Cu, Ni, Pb,
      Zn, Hg, and Cr content specified by Turkish regulations. A high Ca/Mg molar ratio
      and the presence of K, Na, and Al affected the efficiency of struvite
      crystallization. The use of oxalic acid resulted in low Ca release, and the metal
      ions that affect struvite purity were eliminated using Donnan dialysis.

PMID- 29168715
TI  - Emission of hydrogen sulfide (H2S) at a waterfall in a sewer: study of main
      factors affecting H2S emission and modeling approaches.
AB  - Hydrogen sulfide (H2S) represents one of the main odorant gases emitted from
      sewer networks. A mathematical model can be a fast and low-cost tool for
      estimating its emission. This study investigates two approaches to modeling H2S
      gas transfer at a waterfall in a discharge manhole. The first approach is based
      on an adaptation of oxygen models for H2S emission at a waterfall and the second
      consists of a new model. An experimental set-up and a statistical data analysis
      allowed the main factors affecting H2S emission to be studied. A new model of the
      emission kinetics was developed using linear regression and taking into account
      H2S liquid concentration, waterfall height and fluid velocity at the outlet pipe
      of a rising main. Its prediction interval was estimated by the residual standard
      deviation (15.6%) up to a rate of 2.3 g H2S.h-1. Finally, data coming from four
      sampling campaigns on sewer networks were used to perform simulations and compare
      predictions of all developed models.

PMID- 29168716
TI  - Ozonation for the removal of bisphenol A.
AB  - The mechanism of byproduct formation and oxidation pathway of bisphenol A (BPA)
      during ozonation process have been compared under acidic, neutral and alkaline
      conditions at an applied ozone dose of 5.3 mg.L-1 min-1. Alkaline conditions
      promoted the fastest removal and the pseudo first-order reaction rate constant
      was calculated as 0.15 min-1. Complete removal under alkaline conditions (after
      30 minutes of reaction time) was achieved with 1.59 mg ozone per mg BPA and 52%
      mineralization was achieved at 6.04 mg ozone application per mg total organic
      carbon (after 90 minutes of reaction time). Hydroxyl radical dominated
      degradation pathway (pH 10) resulted with opening of ring-structured products
      into Heptanoic acid, methyl ester. Sixty per cent BPA removal occurred under
      acidic conditions where the ozone was dominant and formation of Cyclohexene-1
      carboxylic acid, ethyl ester, Benzaldehyde, 4-hydroxy-3,5-dimethyl- and 2
      Phenylbenzoquinone were evidenced. Despite the fact that complete removal was
      achieved under neutral conditions, mineralization was not remarkable and both
      hydroxyl radical and ozone-based degradation pattern was evidenced after the
      treatment.

PMID- 29168717
TI  - Cross-linked chitosan/marble powder composites for the adsorption of Dimozol
      Blue.
AB  - Cross-linked chitosan(C)/marble powder (M) composites with different weight ratio
      percentage (C100M0, C70M30, C50M50, and C30M70) were prepared from marble powder
      and chitosan and cross-linked using glutaraldehyde. The morphology and the
      surface area of the chitosan/marble powder composites were also characterized
      with a scanning electron microscope (SEM) and Micromeritics (ASAP 2020) BET
      (Brunauer, Emmett and Teller) instrument, respectively. To evaluate the
      adsorption behaviour of the chitosan/marble powder composites, 0.1 g adsorbent
      was added into 50 mL Diamozol Blue BRF %150 (C.I. Reactive Blue 221) solution
      with fixed concentrations (60 mg/L). At equilibrium, the adsorption capacity of
      C100M0, C70M30 and C50M50 for Dimozol Blue was about 27 mg/g and significantly
      greater than that of C30M70. C50M50 composite was more economical than C100M0 and
      C70M30 due to the higher marble powder content, and hence was selected as an
      adsorbent for the removal of Dimozol Blue from aqueous solution. The adsorption
      kinetics and equilibrium isotherms of Dimozol Blue onto the chitosan/marble
      powder composites from aqueous solution were investigated. The studies revealed
      that Dimozol Blue dye adsorption was described well by the pseudo-second-order
      and Freundlich isotherm models. The results of this study indicated the
      applicability of the chitosan/marble powder composites for removing industrial
      dyes from aqueous solution.

PMID- 29168718
TI  - Critical flux investigation in treating o/w emulsion by TiO2/Al2O3-PVDF UF
      membrane.
AB  - A standard transmembrane pressure (TMP) step method has been used in membrane
      fouling assessment in tube ultrafiltration (UF) membrane system treating oil
      water (o/w) emulsion operated at constant TMP. Three flux reduction curve with
      different o/w concentration based on TMP variation were concluded by experiment,
      then, to describe fouling behavior and identify the occurrence of fouling in the
      so-called critical flux. Furthermore, sub-critical and super-critical flux
      experiment with a long time was determined, and zero rate of flux reduction
      (dF/dt) was never found during the whole trial period, indicating that critical
      flux in o/w UF process with its strict definition could not be defined in this
      paper. However, quasi-critical flux exists, under which the pollution rate was
      very slow. Moreover, a high-efficiency four steps cleaning method: mechanic
      scraping, pure water wash, pure water reverse wash, and dosing cleaning, was
      explored. It concluded that critical flux in real o/w UF system determined by TMP
      step method can be used to predict long-term critical behavior with useful data
      on fouling propensity.

PMID- 29168719
TI  - Influence of ultrasound on the heterogeneous Fenton-like oxidation of acetic
      acid.
AB  - The main objective of this study is to investigate the effect of ultrasound on
      the heterogeneous Fenton-like oxidation of acetic acid, which is one of the most
      resistant carboxylic acids to oxidation. For this purpose, firstly, the
      degradation of acetic acid was examined by using ultrasound alone and the effects
      of different parameters such as: type of sonication system, ultrasonic power, and
      addition of H2O2 were investigated on the degradation of acetic acid. There was
      no chemical oxygen demand (COD) reduction in the presence of sonication alone. In
      the presence of the heterogeneous Fenton-like oxidation process alone, at 303 K,
      COD reduction reached only 7.1% after 2 h of reaction. However, the combination
      of the heterogeneous Fenton-like oxidation process with ultrasound increased the
      COD reduction from 7.1% to 25.5% after 2 h of reaction in an ultrasonic bath
      operated at 40 kHz, while the COD reduction only increased from 7.1% to 8.9% in
      the ultrasonic reactor operated at 850 kHz. This result indicates that the hybrid
      process of ultrasound and heterogeneous Fenton-like oxidation is a promising
      process to degrade acetic acid.

PMID- 29168720
TI  - Assessment of uncertainty in discrete fracture network modeling using
      probabilistic distribution method.
AB  - There have been widespread concerns about solute transport problems in fractured
      media, e.g. the disposal of high-level radioactive waste in geological fractured
      rocks. Numerical simulation of particle tracking is gradually being employed to
      address these issues. Traditional predictions of radioactive waste transport
      using discrete fracture network (DFN) models often consider one particular
      realization of the fracture distribution based on fracture statistic features.
      This significantly underestimates the uncertainty of the risk of radioactive
      waste deposit evaluation. To adequately assess the uncertainty during the DFN
      modeling in a potential site for the disposal of high-level radioactive waste,
      this paper utilized the probabilistic distribution method (PDM). The method was
      applied to evaluate the risk of nuclear waste deposit in Beishan, China.
      Moreover, the impact of the number of realizations on the simulation results was
      analyzed. In particular, the differences between the modeling results of one
      realization and multiple realizations were demonstrated. Probabilistic
      distributions of 20 realizations at different times were also obtained. The
      results showed that the employed PDM can be used to describe the ranges of the
      contaminant particle transport. The high-possibility contaminated areas near the
      release point were more concentrated than the farther areas after 5E6 days, which
      was 25,400 m2.

PMID- 29168721
TI  - Reduction dye in paint and construction chemicals wastewater by improved
      coagulation-flocculation process.
AB  - A coagulation-flocculation process was applied to wastewater of paint and
      construction chemicals producing factory in Turkey. Ferric chloride was used as
      coagulant and several natural based materials, namely limestone, pumice,
      sepiolite, bentonite and mussel shell were used as flocculant aids. The effects
      of dosage of flocculant aids on the pH, color and electrical conductivity of
      wastewater were studied. The experimental results showed that the treatment with
      all substances was very effective. The pHs of treated wastewater were obtained in
      the range of 5-7 without needing pH adjustment process. Fifteen Pt-Co color
      values were obtained on average, which is similar to pure water clarity. The
      amount of solute in the wastewater was evaluated by the electrical conductivity
      values. According to the results, under the optimum treatment conditions,
      chemical oxygen demands were determined. As a result of the work, the cost of
      chemicals for the wastewater treatment processes has been reduced by about 90%.

PMID- 29168722
TI  - Experimental study of pollutant washoff on a full-scale street section physical
      model.
AB  - This study analyses the mobilization of total suspended solids (TSS) for
      different spatial distributions of sediment load located over the roadway surface
      of a full-scale street section physical model. At the sewer network outlet, flow
      discharges were measured and TSS pollutographs were determined with manual grab
      samples and inferred from turbidity records. In all the tests, the rain duration
      was 5 min and its averaged intensity was 101 mm/h. In addition, solids that were
      not washed off at the end of the experiments were collected from the street
      surface, gully pots and pipes and the mass balance error was checked. The
      experiments were configured to assess the influence of the initial load, spatial
      distribution method, distance from gully pot and distribution area dimensions on
      the TSS washoff. The study showed that sediment initial load and distribution
      cannot explain completely pollutant washoff processes because other variables
      such as the spatial rainfall distribution or the runoff depth also affect to the
      outlet pollutographs and system mass balances.

PMID- 29168723
TI  - Agro-ecological compensation of watershed based on emergy.
AB  - The paper aims at providing a framework to calculate the agro-eco-compensation
      standard based on the systems agro-ecological concept of embodied energy as
      emergy. We have proposed a calculation system of eco-compensation standard for
      sustainable agricultural development based on the convertibility between emergy
      and price. According to our calculation, the total energy of agricultural
      production in Yongding River Basin was 3.45 E + 16 Sej/ha (the unit emergy value,
      expressed in solar emergy joules per unit) in terms of the renewable resources,
      nonrenewable resources, material inputs, and service costs. The energy of
      renewable and nonrenewable resources was 1.59 E + 16 and 1.86E + 16 Sej/ha,
      respectively. The ESI (environmental sustainability index) of the study area was
      0.1056, indicating that its agricultural production was in a seriously
      unsustainable condition. To realize the sustainable agricultural production in
      the watershed, the downstream governments should pay $21.81 M (Y135 million)
      approximately to upstream governments for water and soil conservation. The
      results of the present study suggested that the emergy-based calculation method
      of agro-eco-compensation standard is feasible to a certain degree.

PMID- 29168724
TI  - Ca removal and Mg recovery from flue gas desulfurization (FGD) wastewater by
      selective precipitation.
AB  - Selective removal of Ca and recovery of Mg by precipitation from flue gas
      desulfurization (FGD) wastewater has been investigated. Thermodynamic analysis of
      four possible additives, Na2CO3, Na2C2O4, NaF and Na2SO4, indicated that both
      carbonate and oxalate could potentially provide effective separation of Ca via
      precipitation from Mg in FGD wastewater. However, it was found experimentally
      that the carbonate system was not as effective as oxalate in this regard. The
      oxalate system performed considerably better, with Ca removal efficiency of 96%
      being obtained, with little Mg inclusion at pH 6.0 when the dosage was *1.4 the
      stoichiometric requirement. On this basis, the subsequent recovery process for Mg
      was carried out using NaOH with two-step precipitation. The product was confirmed
      to be Mg(OH)2 (using X-ray diffraction and thermo gravimetric analysis) with
      elemental analysis suggesting a purity of 99.3 wt.%.

PMID- 29168725
TI  - Synthesis and application of surface-modified NiFe nanoparticles as a new
      magnetic nano adsorbent for the removal of nickel ions from aqueous solution.
AB  - Surface-modified magnetic Ni2.33Fe alloy nanoparticles were prepared using a
      hydrothermal method. Thermogravimetric analysis (TG) and Fourier transform
      infrared spectroscopy (FTIR) tests demonstrated that the surface was successfully
      modified by sodium citrate. The surface-modified particles can be used for
      removing nickel ions from aqueous solution. The adsorption kinetics studies were
      performed and the pseudo-second-order kinetic model successfully described the
      kinetic data. The diffusion model indicated the adsorption was regulated by both
      surface and intraparticle diffusion processes. The Freundlich and Langmuir
      adsorption models were adopted for the mathematical description of adsorption
      equilibrium, and it was found that the experimental data fitted very well to the
      Freundlich model.

PMID- 29168726
TI  - Nutrient modeling for a semi-intensive IMC pond: an MS-Excel approach.
AB  - Semi-intensive Indian Major Carp (IMC) culture was practised in polythene lined
      dugout ponds at the Aquacultural Farm of Indian Institute of Technology,
      Kharagpur, West Bengal for 3 consecutive years at three different stocking
      densities (S.D), viz., 20,000, 35,000 and 50,000 numbers of fingerlings per
      hectare of water spread area. Fingerlings of Catla, Rohu and Mrigal were raised
      at a stocking ratio of 4:3:3. Total ammonia nitrogen (TAN) value along with other
      fishpond water quality parameters was monitored at 1 day intervals to ensure a
      good water ecosystem for a better fish growth. Water exchange was carried out
      before the TAN reached the critical limit. Field data on TAN obtained from the
      cultured fishponds stocked with three different stocking densities were used to
      study the dynamics of TAN. A developed model used to study the nutrient dynamics
      in shrimp pond was used to validate the observed data in the IMC pond ecosystem.
      Two years of observed TAN data were used to calibrate the spreadsheet model and
      the same model was validated using the third year observed data. The manual
      calibration based on the trial and error process of parameters adjustments was
      used and several simulations were performed by changing the model parameters.
      After adjustment of each parameter, the simulated and measured values of the
      water quality parameters were compared to judge the improvement in the model
      prediction. Forward finite difference discretization method was used in a MS
      Excel spreadsheet to calibrate and validate the model for obtaining the TAN
      levels during the culture period. Observed data from the cultured fishponds of
      three different S.D were used to standardize 13 model parameters. The efficiency
      of the developed spreadsheet model was found to be more than 90% for the TAN
      estimation in the IMC cultured fishponds.

PMID- 29168727
TI  - A Supercluster of Neutralizing Epitopes at the Interface of Ricin's Enzymatic
      (RTA) and Binding (RTB) Subunits.
AB  - As part of an effort to engineer ricin antitoxins and immunotherapies, we
      previously produced and characterized a collection of phage-displayed, heavy
      chain-only antibodies (VHHs) from alpacas that had been immunized with ricin
      antigens. In our initial screens, we identified nine VHHs directed against ricin
      toxin's binding subunit (RTB), but only one, JIZ-B7, had toxin-neutralizing
      activity. Linking JIZ-B7 to different VHHs against ricin's enzymatic subunit
      (RTA) resulted in several bispecific antibodies with potent toxin-neutralizing
      activity in vitro and in vivo. JIZ-B7 may therefore be an integral component of a
      future VHH-based neutralizing agent (VNA) for ricin toxin. In this study, we now
      localize, using competitive ELISA, JIZ-B7's epitope to a region of RTB's domain 2
      sandwiched between the high-affinity galactose/N-acetylgalactosamine (Gal/GalNAc)
      binding site and the boundary of a neutralizing hotspot on RTA known as cluster
      II. Analysis of additional RTB (n = 8)- and holotoxin (n = 4)-specific VHHs from
      a recent series of screens identified a "supercluster" of neutralizing epitopes
      at the RTA-RTB interface. Among the VHHs tested, toxin-neutralizing activity was
      most closely associated with epitope proximity to RTA, and not interference with
      RTB's ability to engage Gal/GalNAc receptors. We conclude that JIZ-B7 is
      representative of a larger group of potent toxin-neutralizing antibodies,
      possibly including many described in the literature dating back several decades,
      that recognize tertiary and possibly quaternary epitopes located at the RTA-RTB
      interface and that target a region of vulnerability on ricin toxin.

PMID- 29168729
TI  - The Mental Homologies of Mammals. Towards an Understanding of Another Mammals
      World View.
AB  - Mammals' mental homologies include that they look after their young, suckle and
      protect them; they acquire information about the world by learning. They have
      five types of sensory receptors and a brain to analyze the information and they
      feel: that is they are sentient. Mental homologies have been largely ignored by
      behavioural scientists since Darwin because of certain historical beliefs. This
      however has not been the case for people who have had to do with non-human
      mammals who have long recognized their mental similarities to humans. As a
      result, behavioural science has sponsored some inappropriate research (examples
      are given). The study of another mammal species epistemology, (knowledge and
      world view) requires a recognition of these mental homologies. The result of a 25
      year multi-disciplinary study indicates that there are nine mammalian mental
      homologies which define mammals. These are discussed and reviewed and further
      mental aptitudes which logically follow from these are pointed out. A Conditional
      Anthropomorphic approach is proposed. By recognizing the body/mind, whole "being"
      homologies of mammals, we can advance in understanding other mammal species' and
      individual's epistemology (world view), and consequently better their welfare and
      enrich our own lives.

PMID- 29168728
TI  - Interference of HTLV-1 Tax Protein with Cell Polarity Regulators: Defining the
      Subcellular Localization of the Tax-DLG1 Interaction.
AB  - Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral
      replication and cell transformation. Tax localizes in the nucleus and cytoplasm
      in association with organelles. Some activities of Tax depend on interactions
      with PDZ (PSD-95/Discs Large/Z0-1) domain-containing proteins such as Discs large
      protein 1 (DLG1) which is involved in cell polarity and proliferation. The DLG1
      interaction results in a cytoplasmic co-localization pattern resembling vesicular
      aggregates, the nature of which is still unknown. To further explore the role of
      PDZ proteins in HTLV-1 cell transformation, we deeply investigated the Tax-DLG1
      association. By fluorescence resonance energy transfer (FRET), we detected, for
      the first time, the direct binding of Tax to DLG1 within the cell. We showed that
      the interaction specifically affects the cellular distribution of not only DLG1,
      but also Tax. After studying different cell structures, we demonstrated that the
      aggregates distribute into the Golgi apparatus in spatial association with the
      microtubule-organizing center (MTOC). This study contributes to understand the
      biological significance of Tax-PDZ interactions.

PMID- 29168730
TI  - Comparative Proteomics Analyses of Pollination Response in Endangered Orchid
      Species Dendrobium Chrysanthum.
AB  - Pollination is a crucial stage in plant reproductive process. The self
      compatibility (SC) and self-incompatibility (SI) mechanisms determined the plant
      genetic diversity and species survival. D. chrysanthum is a highly valued
      ornamental and traditional herbal orchid in Asia but has been declared
      endangered. The sexual reproduction in D. chrysanthum relies on the compatibility
      of pollination. To provide a better understanding of the mechanism of
      pollination, the differentially expressed proteins (DEP) between the self
      pollination (SP) and cross-pollination (CP) pistil of D. chrysanthum were
      investigated using proteomic approaches-two-dimensional electrophoresis (2-DE)
      coupled with tandem mass spectrometry technique. A total of 54 DEP spots were
      identified in the two-dimensional electrophoresis (2-DE) maps between the SP and
      CP. Gene ontology analysis revealed an array of proteins belonging to following
      different functional categories: metabolic process (8.94%), response to stimulus
      (5.69%), biosynthetic process (4.07%), protein folding (3.25%) and transport
      (3.25%). Identification of these DEPs at the early response stage of pollination
      will hopefully provide new insights in the mechanism of pollination response and
      help for the conservation of the orchid species.

PMID- 29168732
TI  - Viral Infection and Apoptosis.
AB  - Viruses are master molecular manipulators, and evolved to thrive and survive in
      all species.[...].

PMID- 29168731
TI  - Factors Influencing the Phenotypic Characterization of the Oral Marker, PROP.
AB  - In the last several decades, the genetic ability to taste the bitter compound, 6
      n-propyltiouracil (PROP) has attracted considerable attention as a model for
      understanding individual differences in taste perception, and as an oral marker
      for food preferences and eating behavior that ultimately impacts nutritional
      status and health. However, some studies do not support this role. This review
      describes common factors that can influence the characterization of this
      phenotype including: (1) changes in taste sensitivity with increasing age; (2)
      gender differences in taste perception; and (3) effects of smoking and obesity.
      We suggest that attention to these factors during PROP screening could strengthen
      the associations between this phenotype and a variety of health outcomes ranging
      from variation in body composition to oral health and cancer risk.

PMID- 29168733
TI  - Single-Shot Detection of Neurotransmitters in Whole-Blood Samples by Means of the
      Heat-Transfer Method in Combination with Synthetic Receptors.
AB  - Serotonin is an important neurotransmitter that plays a major role in the
      pathogenesis of a variety of conditions, including psychiatric disorders. The
      detection of serotonin typically relies on high-performance liquid chromatography
      (HPLC), an expensive technique that requires sophisticated equipment and trained
      personnel, and is not suitable for point-of-care applications. In this
      contribution, we introduce a novel sensor platform that can measure spiked
      neurotransmitter concentrations in whole blood samples in a fast and low-cost
      manner by combining synthetic receptors with a thermal readout technique-the heat
      transfer method. In addition, the design of a miniaturized version of the sensing
      platform is presented that aims to bridge the gap between measurements in a
      laboratory setting and point-of-care measurements. This fully automated and
      integrated, user-friendly design features a capillary pumping unit that is
      compatible with point-of-care sampling techniques such as a blood lancet device
      (sample volume-between 50 uL and 300 uL). Sample pre-treatment is limited to the
      addition of an anti-coagulant. With this fully integrated setup, it is possible
      to successfully discriminate serotonin from a competitor neurotransmitter
      (histamine) in whole blood samples. This is the first demonstration of a point-of
      care ready device based on synthetic receptors for the screening of
      neurotransmitters in complex matrices, illustrating the sensor's potential
      application in clinical research and diagnosis of e.g., early stage depression.

PMID- 29168734
TI  - Impact of Ohmic-Assisted Decoction on Bioactive Components Extracted from Yacon
      (Smallanthus sonchifolius Poepp.) Leaves: Comparison with Conventional Decoction.
AB  - Yacon (Smallanthus sonchifolius Poepp.) leaves are a potentially rich source of
      bioactive compounds, such as phenolic acids and flavonoids. In this study, the
      effect of the extraction method (ohmic-assisted decoction (OH-DE) and decoction
      (DE)), yacon cultivar (red and white), and leaf age (young and old) on the
      quality/quantity of extracted phytochemicals were investigated. Extraction yield,
      energy consumption, total phenolic content (TPC), total flavonoid content (TFC),
      ABTS and DPPH radical scavenging activity, and ferric reducing antioxidant power
      (FRAP) were determined. Additionally, HPLC-DAD was used to identify the major
      individual phenolic and flavonoid compounds of yacon leaves. The results showed
      that a three-way interaction of process-variables (extraction method*yacon
      cultivar*age of leaves) influenced the extraction yield, TPC, TFC, ABTS, and DPPH
      radical scavenging activity, and FRAP, significantly (p < 0.05). However, energy
      consumption of the extraction process was only affected by method of extraction
      (p < 0.05) and was halved when OH-DE was applied as compared to DE alone.
      Additionally, the phytochemical quality of extracts was either improved or
      comparable when OH-DE was used for extraction. Also, it was shown that yacon
      leaves contained considerable amounts of caffeic acid, chlorogenic acid, ferrulic
      acid, myricetin, p-coumaric acid, and rutin, while leaves of the red cultivar had
      higher contents of each compound compared to leaves of the white cultivar.

PMID- 29168735
TI  - A Polar Initial Alignment Algorithm for Unmanned Underwater Vehicles.
AB  - Due to its highly autonomy, the strapdown inertial navigation system (SINS) is
      widely used in unmanned underwater vehicles (UUV) navigation. Initial alignment
      is crucial because the initial alignment results will be used as the initial SINS
      value, which might affect the subsequent SINS results. Due to the rapid
      convergence of Earth meridians, there is a calculation overflow in conventional
      initial alignment algorithms, making conventional initial algorithms are invalid
      for polar UUV navigation. To overcome these problems, a polar initial alignment
      algorithm for UUV is proposed in this paper, which consists of coarse and fine
      alignment algorithms. Based on the principle of the conical slow drift of
      gravity, the coarse alignment algorithm is derived under the grid frame. By
      choosing the velocity and attitude as the measurement, the fine alignment with
      the Kalman filter (KF) is derived under the grid frame. Simulation and experiment
      are realized among polar, conventional and transversal initial alignment
      algorithms for polar UUV navigation. Results demonstrate that the proposed polar
      initial alignment algorithm can complete the initial alignment of UUV in the
      polar region rapidly and accurately.

PMID- 29168737
TI  - Prevalence and Predictors of Subclinical Micronutrient Deficiency in German Older
      Adults: Results from the Population-Based KORA-Age Study.
AB  - Subclinical micronutrient deficiency in older adults is associated with chronic
      age-related diseases and adverse functional outcomes. In Germany, the older
      population is at risk of insufficient micronutrient intake, but representative
      studies on micronutrient status in old and very old adults are scarce. This
      study's objectives were to estimate the prevalence of subclinical vitamin D,
      folate, vitamin B12 and iron deficiencies among older adults, aged 65 to 93, from
      the KORA-Age study in Augsburg, Germany (n = 1079), and to examine associated
      predictors, using multiple logistic regression. Serum concentrations of 25
      hydroxyvitamin D (25OHD), folate, vitamin B12, and iron were analyzed. The
      prevalence of subclinical vitamin D and vitamin B12 deficiencies were high, with
      52.0% and 27.3% of individuals having low 25OHD (<50 nmol/L) and low vitamin B12
      concentrations (<221 pmol/L), respectively. Furthermore, 11.0% had low iron (men
      <11.6 umol/L, women <9.0 umol/L) and 8.7% had low folate levels (<13.6 nmol/L).
      Common predictors associated with subclinical micronutrient deficiency included
      very old age, physical inactivity, frailty and no/irregular use of supplements.
      Subclinical micronutrient deficiency is a public health concern among KORA-Age
      participants, especially for vitamins D and B12. The predictors identified
      provide further rationale for screening high-risk subgroups and developing
      targeted public health interventions to tackle prevailing micronutrient
      inadequacies among older adults.

PMID- 29168736
TI  - Association between Vitamin Intake during Pregnancy and Risk of Small for
      Gestational Age.
AB  - Pregnancy increases the requirements of certain nutrients, such as vitamins, to
      provide nutrition for the newborn. The aim was to analyze the association between
      dietary intake of vitamins during pregnancy and risk of having a small for
      gestational age (SGA) newborn. A matched case-control study was conducted (518
      cases and 518 controls of pregnant women) in Spain. Dietary vitamin intake during
      pregnancy was assessed using a validated food frequency questionnaire,
      categorized into quintiles. Odds ratios (ORs) and their 95% confidence intervals
      (CI) were estimated with conditional regression logistic models. A protective
      association was observed between maternal dietary intake of vitamins A and D and
      SGA. For vitamin B3 and B6, the observed protective effect was maintained after
      adjusting for potential confounding factors. For vitamin B9, we found only an
      effect in quintiles 3 and 4 (OR = 0.64; 95% CI, 0.41-1.00; OR = 0.58; 95% CI,
      0.37-0.91). Protective effect for vitamin B12 was observed in 4th and 5th
      quintiles (OR = 0.61; 95% CI, 0.39-0.95; OR = 0.68; 95% CI, 0.43-1.04). No
      associations were detected between dietary intake of vitamins B2, E and C intake
      and SGA. Our results suggest a positive association between dietary vitamin
      intake during pregnancy and the weight of the newborn, although more studies are
      necessary and there could be a ceiling effect for higher intakes of some vitamins
      cannot be discarded.

PMID- 29168738
TI  - Therapeutic Potential of Cholera Toxin B Subunit for the Treatment of
      Inflammatory Diseases of the Mucosa.
AB  - Cholera toxin B subunit (CTB) is a mucosal immunomodulatory protein that induces
      robust mucosal and systemic antibody responses. This well-known biological
      activity has been exploited in cholera prevention (as a component of Dukoral(r)
      vaccine) and vaccine development for decades. On the other hand, several studies
      have investigated CTB's immunotherapeutic potential in the treatment of
      inflammatory diseases such as Crohn's disease and asthma. Furthermore, we
      recently found that a variant of CTB could induce colon epithelial wound healing
      in mouse colitis models. This review summarizes the possible mechanisms behind
      CTB's anti-inflammatory activity and discuss how the protein could impact mucosal
      inflammatory disease treatment.

PMID- 29168739
TI  - Early or Late Feeding after ICU Admission?
AB  - The feeding of critically ill patients has recently become a controversial issue,
      as several studies have provided unexpected and contradictory results. Earlier
      beliefs regarding energy requirements in critical illness-especially during the
      initial phase-have been challenged. In the current review, we summarize existing
      evidence about fasting and the impact of early vs. late feeding on the sick
      organism's responses. The most important points are the non-nutritional
      advantages of using the intestine, and recognition that early endogenous energy
      production as an important player in the response must be integrated in the
      nutrient prescription. There is as of yet no bedside tool to monitor dynamics in
      metabolism and the magnitude of the endogenous energy production. Hence, an early
      "full-feeding strategy" exposes patients to involuntary overfeeding, due to the
      absence of an objective measure enabling the adjustment of the nutritional
      therapy. Suggestions for future research and clinical practice are proposed.

PMID- 29168742
TI  - Turning and Radius Deviation Correction for a Hexapod Walking Robot Based on an
      Ant-Inspired Sensory Strategy.
AB  - Abstract: In order to find a common approach to plan the turning of a bio
      inspired hexapod robot, a locomotion strategy for turning and deviation
      correction of a hexapod walking robot based on the biological behavior and
      sensory strategy of ants. A series of experiments using ants were carried out
      where the gait and the movement form of ants was studied. Taking the results of
      the ant experiments as inspiration by imitating the behavior of ants during
      turning, an extended turning algorithm based on arbitrary gait was proposed.
      Furthermore, after the observation of the radius adjustment of ants during
      turning, a radius correction algorithm based on the arbitrary gait of the hexapod
      robot was raised. The radius correction surface function was generated by fitting
      the correction data, which made it possible for the robot to move in an outdoor
      environment without the positioning system and environment model. The proposed
      algorithm was verified on the hexapod robot experimental platform. The turning
      and radius correction experiment of the robot with several gaits were carried
      out. The results indicated that the robot could follow the ideal radius and
      maintain stability, and the proposed ant-inspired turning strategy could easily
      make free turns with an arbitrary gait.

PMID- 29168740
TI  - Dietary Intake of Cadmium, Lead and Mercury and Its Association with Bone Health
      in Healthy Premenopausal Women.
AB  - The bone is one of the relevant target organs of heavy metals, and heavy metal
      toxicity is associated with several degenerative processes, such osteoporosis and
      bone mineral alterations, that could lead to fractures. We aimed to study a
      presumed relationship between bone density, evaluated by quantitative bone
      ultrasound (QUS), dual-energy X-ray absorptiometry (DXA) and peripheral
      quantitative computed tomography (pQCT) and the dietary intake of cadmium, lead
      and mercury in healthy premenopausal women. A total of 158 healthy, non-smoking,
      premenopausal women were incorporated into the study. A validated food frequency
      questionnaire (FFQ) was administered to assess intake during the preceding seven
      days. The median predicted dietary cadmium intake among the 158 women studied was
      25.29 MUg/day (18.62-35.00) and 2.74 MUg/kg body weight/week (b.w./w) (1.92
      3.83). Dietary lead intake was 43.85 MUg/day (35.09-51.45) and 4.82 MUg/kg b.w./w
      (3.67-6.13). The observed dietary mercury intake was 9.55 MUg/day (7.18-13.57)
      and 1.02 MUg/kg b.w./w (0.71-1.48). Comparisons, in terms of heavy metal intake,
      showed no significant results after further adjusting for energy intake. No
      statistically significant correlations between heavy metal intake and the QUS,
      DXA and pQCT parameters were observed. Levels of dietary exposure of cadmium,
      lead and mercury were mostly within the recommendations. We did not find
      associations between the QUS, DXA and pQCT parameters and the dietary intake of
      the studied heavy metals in healthy premenopausal women.

PMID- 29168741
TI  - Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels
      and Cognition in Aging.
AB  - The effects of tyrosine on plasma response and cognition in aging are unknown. We
      assessed the dose-dependent response to tyrosine administration in older adults
      in both plasma tyrosine concentrations and working memory performance. In this
      double blind randomized cross-over trial 17 older adults (aged 60-75 years)
      received a single administration of 100, 150, or 200 mg/kg body weight of
      tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of
      150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined
      before and 90, 120, 150, 180, 210, and 240 min after tyrosine intake. Working
      memory was assessed using the N-back task at 90 min after tyrosine
      administration. Older adults showed a dose-dependent increase in plasma tyrosine
      concentrations (p < 0.001), and the plasma response was higher than for young
      adults with the same dose (p < 0.001). Load-dependent working memory performance
      decreased with higher doses of tyrosine (p = 0.048), especially in older adults
      with greater dose-dependent plasma tyrosine responses (p = 0.035). Our results
      show an age-related increase in plasma tyrosine response, which was associated
      with a dose-dependent decline in cognitive functioning in older adults.

PMID- 29168744
TI  - Stability and Synergistic Effect of Polyaniline/TiO2 Photocatalysts in
      Degradation of Azo Dye in Wastewater.
AB  - The polyaniline/TiO2 (PANI/TiO2) composite photocatalysts were prepared by the in
      situ chemical oxidation of aniline (An) in the presence of TiO2 particles. For
      this purpose, photocatalysts with different amounts of PANI polymer were prepared
      and analysed. Fourier-transform infrared (FT-IR) spectroscopy and
      thermogravimetric (TG) analysis indicated successful synthesis of the PANI
      polymer and its conductivity was also determined. The micrographs of field
      emission scanning electron microscopy (FE-SEM) and transmission electron
      microscopy (TEM) were used to explain the impact of the aniline amount on the
      aggregation process during the synthesis of the composites. The smallest size of
      aggregates was obtained for the photocatalysts with 15% of PANI (15PANI/TiO2) due
      to the formation of homogenous PANI. The photocatalytic activity of studied
      PANI/TiO2 photocatalysts was validated by monitoring the discoloration and
      mineralization of Reactive Red azo dye (RR45) in wastewater. The 15PANI/TiO2
      sample presented the highest photocatalytic efficiency under ultraviolet A (UVA)
      irradiation, in comparison to pure TiO2. This was explained by the formation of
      uniformly dispersed PANI on the TiO2 particles, which was responsible for the
      synergistic PANI-TiO2 effect.

PMID- 29168743
TI  - Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole
      Derivatives.
AB  - Azole-based antifungal agents constitute one of the important classes of
      antifungal drugs. Hence, in the present work, 12 new benzimidazole-thiazole
      derivatives 3a-3l were synthesized to evaluate their anticandidal activity
      against C.albicans, C.glabrata, C.krusei, and C.parapsilopsis. The structures of
      the newly synthesized compounds 3a-3l were confirmed by IR, 1H-NMR, 13C-NMR, and
      ESI-MS spectroscopic methods. ADME parameters of synthesized compounds 3a-3l were
      predicted by an in-slico study and it was determined that all synthesized
      compounds may have a good pharmacokinetic profile. In the anticandidal activity
      studies, compounds 3c and 3d were found to be the most active compounds against
      all Candida species. In addition, cytoxicity studies showed that these compounds
      are nontoxic with a IC50 value higher than 500 ug/mL. The effect of compounds 3c
      and 3d on the ergosterol level of C.albicans was determined by an LC-MS-MS
      method. It was observed that both compounds cause a decrease in the ergosterol
      level. A molecular docking study including binding modes of 3c to lanosterol
      14alpha-demethylase (CYP51), a key enzyme in ergosterol biosynthesis, was
      performed to elucidate the mechanism of the antifungal action. The docking
      studies revealed that there is a strong interaction between CYP51 and the most
      active compound 3c.

PMID- 29168745
TI  - Interaction of Cholesterol with Perfringolysin O: What Have We Learned from
      Functional Analysis?
AB  - Cholesterol-dependent cytolysins (CDCs) constitute a family of pore-forming
      toxins secreted by Gram-positive bacteria. These toxins form transmembrane pores
      by inserting a large beta-barrel into cholesterol-containing membranes.
      Cholesterol is absolutely required for pore-formation. For most CDCs, binding to
      cholesterol triggers conformational changes that lead to oligomerization and end
      in pore-formation. Perfringolysin O (PFO), secreted by Clostridium perfringens,
      is the prototype for the CDCs. The molecular mechanisms by which cholesterol
      regulates the cytolytic activity of the CDCs are not fully understood. In
      particular, the location of the binding site for cholesterol has remained
      elusive. We have summarized here the current body of knowledge on the CDCs
      cholesterol interaction, with focus on PFO. We have employed sterols in aqueous
      solution to identify structural elements in the cholesterol molecule that are
      critical for its interaction with PFO. In the absence of high-resolution
      structural information, site-directed mutagenesis data combined with binding
      studies performed with different sterols, and molecular modeling are beginning to
      shed light on this interaction.

PMID- 29168747
TI  - Optimization of Dissolution Compartments in a Biorelevant Dissolution Apparatus
      Golem v2, Supported by Multivariate Analysis.
AB  - Biorelevant dissolution instruments represent an important tool for
      pharmaceutical research and development. These instruments are designed to
      simulate the dissolution of drug formulations in conditions most closely
      mimicking the gastrointestinal tract. In this work, we focused on the
      optimization of dissolution compartments/vessels for an updated version of the
      biorelevant dissolution apparatus-Golem v2. We designed eight compartments of
      uniform size but different inner geometry. The dissolution performance of the
      compartments was tested using immediate release caffeine tablets and evaluated by
      standard statistical methods and principal component analysis. Based on two
      phases of dissolution testing (using 250 and 100 mL of dissolution medium), we
      selected two compartment types yielding the highest measurement reproducibility.
      We also confirmed a statistically ssignificant effect of agitation rate and
      dissolution volume on the extent of drug dissolved and measurement
      reproducibility.

PMID- 29168746
TI  - Dissection of Resistance Genes to Pseudomonas syringae pv. phaseolicola in UI3
      Common Bean Cultivar.
AB  - Few quantitative trait loci have been mapped for resistance to Pseudomonas
      syringae pv. phaseolicola in common bean. Two F2 populations were developed from
      the host differential UI3 cultivar. The objective of this study was to further
      characterize the resistance to races 1, 5, 7 and 9 of Psp included in UI3. Using
      a QTL mapping approach, 16 and 11 main-effect QTLs for pod and primary leaf
      resistance were located on LG10, explaining up to 90% and 26% of the phenotypic
      variation, respectively. The homologous genomic region corresponding to primary
      leaf resistance QTLs detected tested positive for the presence of resistance
      associated gene cluster encoding nucleotide-binding and leucine-rich repeat (NL),
      Natural Resistance Associated Macrophage (NRAMP) and Pentatricopeptide Repeat
      family (PPR) proteins. It is worth noting that the main effect QTLs for
      resistance in pod were located inside a 3.5 Mb genomic region that included the
      Phvul.010G021200 gene, which encodes a protein that has the highest sequence
      similarity to the RIN4 gene of Arabidopsis, and can be considered an important
      candidate gene for the organ-specific QTLs identified here. These results support
      that resistance to Psp from UI3 might result from the immune response activated
      by combinations of R proteins, and suggest the guard model as an important
      mechanism in pod resistance to halo blight. The candidate genes identified here
      warrant functional studies that will help in characterizing the actual defense
      gene(s) in UI3 genotype.

PMID- 29168749
TI  - Positron Annihilation and Complementary Studies of Copper Sandblasted with
      Alumina Particles at Different Pressures.
AB  - Positron annihilation spectroscopy and complementary methods were used to detect
      changes induced by sandblasting of alumina particles at different pressures
      varying from 1 to 6 bar in pure well-annealed copper. The positron lifetime
      measurements revealed existence of dislocations and vacancy clusters in the
      adjoined surface layer. The presence of retained alumina particles in the copper
      at the depth below 50 um was found in the SEM pictures and also in the
      annihilation line shape parameter profiles measured in the etching experiment.
      The profiles show us that the total depth of damaged zones induced by
      sandblasting of alumina particles ranges from 140 um up to ca. 800 um and it
      depends on the applied pressure. The work-hardening of the adjoined surface layer
      was found in the microhardness measurements at the cross-section of the
      sandblasted samples.

PMID- 29168748
TI  - Variety and Dynamics of Proteoforms in the Human Proteome: Aspects of Markers for
      Hepatocellular Carcinoma.
AB  - We have previously developed an approach, where two-dimensional gel
      electrophoresis (2DE) was used, followed by sectional analysis of the whole gel
      using high-resolution nano-liquid chromatography-mass spectrometry (ESI LC
      MS/MS). In this study, we applied this approach on the panoramic analysis of
      proteins and their proteoforms from normal (liver) and cancer (HepG2) cells. This
      allowed us to detect, in a single proteome, about 20,000 proteoforms coded by
      more than 4000 genes. A set of 3D-graphs showing distribution of these
      proteoforms in 2DE maps (profiles) was generated. A comparative analysis of these
      profiles between normal and cancer cells showed high variability and dynamics of
      many proteins. Among these proteins, there are some well-known features like
      alpha-fetoprotein (FETA) or glypican-3 (GPC3) and potential hepatocellular
      carcinoma (HCC) markers. More detailed information about their proteoforms could
      be used for generation of panels of more specific biomarkers.

PMID- 29168750
TI  - Deep Convolutional Neural Network-Based Early Automated Detection of Diabetic
      Retinopathy Using Fundus Image.
AB  - The automatic detection of diabetic retinopathy is of vital importance, as it is
      the main cause of irreversible vision loss in the working-age population in the
      developed world. The early detection of diabetic retinopathy occurrence can be
      very helpful for clinical treatment; although several different feature
      extraction approaches have been proposed, the classification task for retinal
      images is still tedious even for those trained clinicians. Recently, deep
      convolutional neural networks have manifested superior performance in image
      classification compared to previous handcrafted feature-based image
      classification methods. Thus, in this paper, we explored the use of deep
      convolutional neural network methodology for the automatic classification of
      diabetic retinopathy using color fundus image, and obtained an accuracy of 94.5%
      on our dataset, outperforming the results obtained by using classical approaches.

PMID- 29168752
TI  - Enological Tannin Effect on Red Wine Color and Pigment Composition and Relevance
      of the Yeast Fermentation Products.
AB  - Enological tannins are widely used in the winemaking process either to improve
      different wine characteristics (color stability, among others) or to compensate
      for low tannin levels. In this work, the influence of the addition of two
      different enological tannins, mainly composed of hydrolysable (ellagitannins) and
      condensed tannins, on the evolution of color and pigment composition of two
      different types of model systems containing the five main grape anthocyanins was
      studied. In addition, the effect of the addition of an enological tannin on the
      color and pigment composition of red wines made from Vitis vinifera L. cv
      Tempranillo grapes was also studied by high-performance liquid chromatography
      with diode array detection coupled to mass spectrometry (HPLC-DAD-MS). Results
      showed that, in model systems, the addition of the enological tannin favored the
      formation of anthocyanin-derived pigments, such as A-type and B-type vitisins and
      flavanol-anthocyanin condensation products, provided that the yeast precursors
      were previously supplied. Moreover, model systems containing the enological
      tannins were darker and showed higher values of chroma at the end of the study
      than control ones. The higher formation of these anthocyanin-derived pigments was
      also observed in the red wines containing the enological tannin. Moreover, these
      wine also showed lower lightness (L*) values and higher chroma (C*ab) values than
      control wines, indicating a higher stabilization of color.

PMID- 29168751
TI  - A Strategy for Preparative Separation of 10 Lignans from Justicia procumbens L.
      by High-Speed Counter-Current Chromatography.
AB  - Ten compounds, including three lignan glycosides and seven lignans, were purified
      from Justicia procumbens L. in 8 h using an efficient strategy based on high
      speed counter-current chromatography (HSCCC). The two-phase solvent system
      composed of petroleum-ethyl acetate-methanol-H2O (1:0.7:1:0.7, v/v) was firstly
      employed to separate the crude extract (320 mg), from which 19.3 mg of justicidin
      B (f), 10.8 mg of justicidin A (g), 13.9 mg of 6'-hydroxyjusticidin C (h), 7.7 mg
      of justicidin E (i), 6.3 mg of lignan J1 (j) were obtained with 91.3 mg of
      enriched mixture of compounds a-e. The enriched mixture (91.3 mg) was further
      separated using the solvent system consisting of petroleum-ethyl acetate-methanol
      H2O (3:3.8:3:3.8, v/v), yielding 12.1 mg of procumbenoside E (a); 7.6 mg of
      diphyllin-1-O-beta-d-apiofuranoside (b); 7.4 mg of diphyllin (c); 8.3 mg of 6'
      hydroxy justicidin B (d); and 7.9 mg of diphyllin acetyl apioside (e). The
      purities of the 10 components were all above 94%, and their structures were
      identified by NMR and ESI-MS spectra. The results demonstrated that the strategy
      based on HSCCC for the separation of lignans and their glycosides was efficient
      and rapid.

PMID- 29168753
TI  - Recyclable Magnetic Titania Nanocomposite from Ilmenite with Enhanced
      Photocatalytic Activity.
AB  - Using ilmenite as a raw material, iron was converted into Fe3O4 magnetic fluid,
      which further was combined with titanium filtrate by a solvothermal method.
      Finally Fe3O4/TiO2 nanocomposites with the uniform size of 100-200 nm were
      prepared. This approach uses rich, inexpensive ilmenite as a titanium and iron
      source, which effectively reduces the production cost. The crystal structure,
      chemical properties and morphologies of the products were characterized by SEM,
      TEM, XRD, FTIR, BET, UV-Vis, XPS and VSM. The novel photocatalyst composed of
      face-centered cubic Fe3O4 and body-centered tetragonal anatase-TiO2 exhibits a
      spherical shape with porous structures, superparamagnetic behavior and strong
      absorption in the visible light range. Using the degradation reaction of
      Rhodamine B (RhB) to evaluate the photocatalytic performance, the results suggest
      that Fe3O4/TiO2 nanocomposites exhibit excellent photocatalytic activities and
      stability under visible light and solar light. Moreover, the magnetic titania
      nanocomposites displayed good magnetic response and were recoverable over several
      cycles. Based on the trapping experiments, the main active species in the
      photocatalytic reaction were confirmed and the possible photocatalytic mechanism
      of RhB with magnetic titania was proposed. The enhanced photocatalytic activity
      and stability, combined with excellent magnetic recoverability, make the prepared
      nanocomposite a potential candidate in wastewater purification.

PMID- 29168754
TI  - A Bioinformatic Pipeline for Monitoring of the Mutational Stability of Viral Drug
      Targets with Deep-Sequencing Technology.
AB  - The efficient development of antiviral drugs, including efficient antiviral small
      interfering RNAs (siRNAs), requires continuous monitoring of the strict
      correspondence between a drug and the related highly variable viral DNA/RNA
      target(s). Deep sequencing is able to provide an assessment of both the general
      target conservation and the frequency of particular mutations in the different
      target sites. The aim of this study was to develop a reliable bioinformatic
      pipeline for the analysis of millions of short, deep sequencing reads
      corresponding to selected highly variable viral sequences that are drug
      target(s). The suggested bioinformatic pipeline combines the available programs
      and the ad hoc scripts based on an original algorithm of the search for the
      conserved targets in the deep sequencing data. We also present the statistical
      criteria for the threshold of reliable mutation detection and for the assessment
      of variations between corresponding data sets. These criteria are robust against
      the possible sequencing errors in the reads. As an example, the bioinformatic
      pipeline is applied to the study of the conservation of RNA interference (RNAi)
      targets in human immunodeficiency virus 1 (HIV-1) subtype A. The developed
      pipeline is freely available to download at the website http://virmut.eimb.ru/.
      Brief comments and comparisons between VirMut and other pipelines are also
      presented.

PMID- 29168756
TI  - Hierarchical Mn2O3 Microspheres In-Situ Coated with Carbon for Supercapacitors
      with Highly Enhanced Performances.
AB  - Porous Mn2O3 microspheres have been synthesized and in-situ coated with amorphous
      carbon to form hierarchical C@Mn2O3 microspheres by first producing MnCO3
      microspheres in solvothermal reactions, and then annealing at 500  degrees C. The
      self-assembly growth of MnCO3 microspheres can generate hollow structures inside
      each of the particles, which can act as micro-reservoirs to store biomass
      glycerol for generating amorphous carbon onto the surfaces of Mn2O3 nanorods
      consisting of microspheres. The C@Mn2O3 microspheres, prepared at 500  degrees C,
      exhibit highly enhanced pseudocapacitive performances when compared to the
      particles after annealed at 400  degrees C and 600  degrees C. Specifically, the
      C@Mn2O3 microspheres prepared at 500  degrees C show high specific capacitances
      of 383.87 F g-1 at current density of 0.5 A g-1, and excellent cycling stability
      of 90.47% of its initial value after cycling for 5000 times. The asymmetric
      supercapacitors assembled with C@Mn2O3 microspheres after annealed at 500 
      degrees C and activated carbon (AC) show an energy density of up to 77.8 Wh kg-1
      at power density of 500.00 W kg-1, and a maximum power density of 20.14 kW kg-1
      at energy density of 46.8 Wh kg-1. We can attribute the enhanced electrochemical
      performances of the materials to their three-dimensional (3D) hierarchical
      structure in-situ coated with carbon.

PMID- 29168757
TI  - Off-Nadir Hyperspectral Sensing for Estimation of Vertical Profile of Leaf
      Chlorophyll Content within Wheat Canopies.
AB  - Monitoring the vertical profile of leaf chlorophyll (Chl) content within winter
      wheat canopies is of significant importance for revealing the real nutritional
      status of the crop. Information on the vertical profile of Chl content is not
      accessible to nadir-viewing remote or proximal sensing. Off-nadir or multi-angle
      sensing would provide effective means to detect leaf Chl content in different
      vertical layers. However, adequate information on the selection of sensitive
      spectral bands and spectral index formulas for vertical leaf Chl content
      estimation is not yet available. In this study, all possible two-band and three
      band combinations over spectral bands in normalized difference vegetation index
      (NDVI)-, simple ratio (SR)- and chlorophyll index (CI)-like types of indices at
      different viewing angles were calculated and assessed for their capability of
      estimating leaf Chl for three vertical layers of wheat canopies. The vertical
      profiles of Chl showed top-down declining trends and the patterns of band
      combinations sensitive to leaf Chl content varied among different vertical
      layers. Results indicated that the combinations of green band (520 nm) with NIR
      bands were efficient in estimating upper leaf Chl content, whereas the red edge
      (695 nm) paired with NIR bands were dominant in quantifying leaf Chl in the lower
      layers. Correlations between published spectral indices and all NDVI-, SR- and CI
      like types of indices and vertical distribution of Chl content showed that
      reflectance measured from 50 degrees , 30 degrees  and 20 degrees  backscattering
      viewing angles were the most promising to obtain information on leaf Chl in the
      upper-, middle-, and bottom-layer, respectively. Three types of optimized
      spectral indices improved the accuracy for vertical leaf Chl content estimation.
      The optimized three-band CI-like index performed the best in the estimation of
      vertical distribution of leaf Chl content, with R2 of 0.84-0.69, and RMSE of 5.37
      5.56 ug/cm2 from the top to the bottom layers, while the optimized SR-like index
      was recommended for the bottom Chl estimation due to its simple and universal
      form. We suggest that it is necessary to take into account the penetration
      characteristic of the light inside the canopy for different Chl absorption
      regions of the spectrum and the formula used to derive spectral index when
      estimating the vertical profile of leaf Chl content using off-nadir hyperspectral
      data.

PMID- 29168755
TI  - Regulation of G2/M Transition by Inhibition of WEE1 and PKMYT1 Kinases.
AB  - In the cell cycle, there are two checkpoint arrests that allow cells to repair
      damaged DNA in order to maintain genomic integrity. Many cancer cells have
      defective G1 checkpoint mechanisms, thus depending on the G2 checkpoint far more
      than normal cells. G2 checkpoint abrogation is therefore a promising concept to
      preferably damage cancerous cells over normal cells. The main factor influencing
      the decision to enter mitosis is a complex composed of Cdk1 and cyclin B.
      Cdk1/CycB is regulated by various feedback mechanisms, in particular inhibitory
      phosphorylations at Thr14 and Tyr15 of Cdk1. In fact, Cdk1/CycB activity is
      restricted by the balance between WEE family kinases and Cdc25 phosphatases. The
      WEE kinase family consists of three proteins: WEE1, PKMYT1, and the less
      important WEE1B. WEE1 exclusively mediates phosphorylation at Tyr15, whereas
      PKMYT1 is dual-specific for Tyr15 as well as Thr14. Inhibition by a small
      molecule inhibitor is therefore proposed to be a promising option since WEE
      kinases bind Cdk1, altering equilibria and thus affecting G2/M transition.

PMID- 29168759
TI  - Experimental Investigation on the Detection of Multiple Surface Cracks Using
      Vibrothermography with a Low-Power Piezoceramic Actuator.
AB  - Vibrothermography often employs a high-power actuator to generate heat on a
      specimen to reveal damage, however, the high-power actuator brings inconvenience
      to the application and possibly introduces additional damage to the inspected
      objects. This study uses a low-power piezoceramic transducer as the actuator of
      vibrothermography and explores its ability to detect multiple surface cracks in a
      metal part. Experiments were conducted on a thin aluminum beam with three cracks
      in different orientations. Detailed analyses of both thermograms and temperature
      data are presented to validate the proposed vibrothermography method. To further
      investigate the performance of the proposed vibrothermography method, we
      experimentally studied the effects of several critical factors, including the
      amplitude of excitation signal, specimen constraints, relative position between
      the transducer and cracks (the transducer is mounted on the same or the opposite
      side with the cracks). The results demonstrate that all cracks can be detected
      conveniently and simultaneously by using the proposed low-power
      vibrothermography. We also found that the magnitude of excitation signal and the
      specimen constraints have a great influence on detection results. Combined with
      effective data processing methods, such as Fourier transformation employed in
      this study, the proposed method provides a promising potential to detect multiple
      cracks on a metal surface in a safe and effective manner.

PMID- 29168758
TI  - The Content of Structural and Trace Elements in the Knee Joint Tissues.
AB  - Many elements are responsible for the balance in bone tissue, including those
      which constitute a substantial proportion of bone mass, i.e., calcium, phosphorus
      and magnesium, as well as minor elements such as strontium. In addition, toxic
      elements acquired via occupational and environmental exposure, e.g., Pb, are
      included in the basic bone tissue composition. The study objective was to
      determine the content of strontium, lead, calcium, phosphorus, sodium and
      magnesium in chosen components of the knee joint, i.e., tibia, femur and
      meniscus. The levels of Sr, Pb, Ca, P, Na and Mg were the highest in the tibia in
      both men and women, whereas the lowest in the meniscus. It should be noted that
      the levels of these elements were by far higher in the tibia and femur as
      compared to the meniscus. In the components of the knee joint, the level of
      strontium showed the greatest variation. Significant statistical differences were
      found between men and women only in the content of lead.

PMID- 29168760
TI  - Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery.
AB  - Mesenchymal stromal cells are a population of undifferentiated multipotent adult
      cells possessing extensive self-renewal properties and the potential to
      differentiate into a variety of mesenchymal lineage cells. They express broad
      anti-inflammatory and immunomodulatory activity on the immune system and after
      transplantation can interact with the surrounding microenvironment, promoting
      tissue healing and regeneration. For this reason, mesenchymal stromal cells have
      been widely used in regenerative medicine, both in preclinical and clinical
      settings. Another clinical application of mesenchymal stromal cells is the
      targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the
      cytotoxic activity against cancer cells and minimizing collateral damage to non
      neoplastic tissues. Mesenchymal stem cells are home to the stroma of several
      primary and metastatic neoplasms and hence can be used as vectors for targeted
      delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing
      systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine
      are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and
      delivered to neoplastic cells, whereas other agents, like pemetrexed, are not
      internalized by mesenchymal stromal cells and therefore are not suitable for
      advanced antineoplastic therapy. This review focuses on the state of the art of
      advanced antineoplastic cell therapy and its future perspectives, emphasizing in
      vitro and in vivo preclinical results and future clinical applications.

PMID- 29168761
TI  - Using a Particle Counter to Inform the Creation of Similar Exposure Groups and
      Sampling Protocols in a Structural Steel Fabrication Facility.
AB  - The objective of this project was to create similar exposure groups (SEGs) for
      occupational monitoring in a structural steel fabrication facility. Qualitative
      SEG formation involved worksite observation, interviews, and audits of materials
      and procedures. These were supplemented with preliminary task-based shop survey
      data collected using a condensation particle counter. A total of six SEGs were
      formed, with recommendations for occupational exposure sampling for five groups,
      as well as ambient sampling recommendations to address areas on the operational
      floor found to have higher particle concentrations. The combination of direct
      reading device data and qualitative SEG formation techniques is a valuable
      approach, as it contains both the monetary and temporal costs of worksite
      exposure monitoring. This approach also provides an empowering in-house analysis
      of potentially problematic areas, and results in the streamlining of occupational
      exposure assessment.

PMID- 29168762
TI  - Dual Roles of Fer Kinase Are Required for Proper Hematopoiesis and Vascular
      Endothelium Organization during Zebrafish Development.
AB  - Fer kinase, a protein involved in the regulation of cell-cell adhesion and
      proliferation, has been shown to be required during invertebrate development and
      has been implicated in leukemia, gastric cancer, and liver cancer. However, in
      vivo roles for Fer during vertebrate development have remained elusive. In this
      study, we bridge the gap between the invertebrate and vertebrate realms by
      showing that Fer kinase is required during zebrafish embryogenesis for normal
      hematopoiesis and vascular organization with distinct kinase dependent and
      independent functions. In situ hybridization, quantitative PCR and fluorescence
      activated cell sorting (FACS) analyses revealed an increase in both erythrocyte
      numbers and gene expression patterns as well as a decrease in the organization of
      vasculature endothelial cells. Furthermore, rescue experiments have shown that
      the regulation of hematopoietic proliferation is dependent on Fer kinase
      activity, while vascular organizing events only require Fer in a kinase
      independent manner. Our data suggest a model in which separate kinase dependent
      and independent functions of Fer act in conjunction with Notch activity in a
      divergent manner for hematopoietic determination and vascular tissue
      organization.

PMID- 29168763
TI  - Micro-Computed-Tomography-Guided Analysis of In Vitro Structural Modifications in
      Two Types of 45S5 Bioactive Glass Based Scaffolds.
AB  - Three-dimensional 45S5 bioactive glass (BG)-based scaffolds are being
      investigated for bone regeneration. Besides structural properties, controlled
      time-dependent alteration of scaffold morphology is crucial to achieve optimal
      scaffold characteristics for successful bone repair. There is no in vitro
      evidence concerning the dependence between structural characteristics and
      dissolution behavior of 45S5 BG-based scaffolds of different morphology. In this
      study, the dissolution behavior of scaffolds fabricated by the foam replica
      method using polyurethane foam (Group A) and maritime sponge Spongia Agaricina
      (Group B) as sacrificial templates was analyzed by micro-computed-tomography
      (uCT). The scaffolds were immersed in Dulbecco's Modified Eagle Medium for 56
      days under static cell culture conditions and underwent uCT-analysis initially,
      and after 7, 14, and 56 days. Group A showed high porosity (91%) and trabecular
      structure formed by macro-pores (average diameter 692 um +/- 72 um). Group-B
      scaffolds were less porous (51%), revealing an optimal pore size distribution
      within the window of 110-500 um pore size diameter, combined with superior
      mechanical stability. Both groups showed similar structural alteration upon
      immersion. Surface area and scaffold volume increased whilst density decreased,
      reflecting initial dissolution followed by hydroxycarbonate-apatite-layer
      formation on the scaffold surfaces. In vitro- and/or in vivo-testing of cell
      seeded BG-scaffolds used in this study should be performed to evaluate the BG
      scaffolds' time-dependent osteogenic properties in relation to the measured in
      vitro structural changes.

PMID- 29168764
TI  - Cross-National Systematic Review of Neonatal Mortality and Postnatal Newborn
      Care: Special Focus on Pakistan.
AB  - The latest nationwide survey of Pakistan showed that considerable progress has
      been made toward reducing all child mortality indicators except neonatal
      mortality. The aim of this study is to compare Pakistan's under-five mortality,
      neonatal mortality, and postnatal newborn care rates with those of other
      countries. Neonatal mortality rates and postnatal newborn care rates from the
      Demographic and Health Surveys (DHSs) of nine low- and middle-income countries
      (LMIC) from Asia and Africa were analyzed. Pakistan's maternal, newborn, and
      child health (MNCH) policies and programs, which have been implemented in the
      country since 1990, were also analyzed. The results highlighted that postnatal
      newborn care in Pakistan was higher compared with the rest of countries, yet its
      neonatal mortality remained the worst. In Zimbabwe, both mortality rates have
      been increasing, whereas the neonatal mortality rates in Nepal and Afghanistan
      remained unchanged. An analysis of Pakistan's MNCH programs showed that there is
      no nationwide policy on neonatal health. There were only a few programs
      concerning the health of newborns, and those were limited in scale. Pakistan's
      example shows that increased coverage of neonatal care without ensuring quality
      is unlikely to improve neonatal survival rates. It is suggested that Pakistan
      needs a comprehensive policy on neonatal health similar to other countries, and
      its effective programs need to be scaled up, in order to obtain better neonatal
      health outcomes.

PMID- 29168765
TI  - Phenylazopyridine as Switch in Photochemical Reactions. A Detailed Computational
      Description of the Mechanism of Its Photoisomerization.
AB  - Azo compounds are organic photochromic systems that have the possibility of
      switching between cis and trans isomers under irradiation. The different
      photochemical properties of these isomers make azo compounds into good light
      triggered switches, and their significantly different geometries make them very
      interesting as components in molecular engines or mechanical switches. For
      instance, azo ligands are used in coordination complexes to trigger
      photoresponsive properties. The light-induced trans-to-cis isomerization of
      phenylazopyridine (PAPy) plays a fundamental role in the room-temperature
      switchable spin crossover of Ni-porphyrin derivatives. In this work, we present a
      computational study developed at the SA-CASSCF/CASPT2 level (State Averaged
      Complete Active Space Self Consistent Field/CAS second order Perturbation Theory)
      to elucidate the mechanism, up to now unknown, of the cis-trans
      photoisomerization of 3-PAPy. We have analyzed the possible reaction pathways
      along its lowest excited states, generated by excitation of one or two electrons
      from the lone pairs of the N atoms of the azo group (nazopi*2 and nazo2pi*2
      states), from a pi delocalized molecular orbital (pipi* state), or from the lone
      pair of the N atom of the pyridine moiety (npypi* state). Our results show that
      the mechanism proceeds mainly along the rotation coordinate in both the nazopi*
      and pipi* excited states, although the nazo2pi*2 state can also be populated
      temporarily, while the npypi* does not intervene in the reaction. For
      rotationally constrained systems, accessible paths to reach the cis minimum along
      planar geometries have also been located, again on the nazopi* and pipi*
      potential energy surfaces, while the nazo2pi*2 and npypi* states are not involved
      in the reaction. The relative energies of the different paths differ from those
      found for azobenzene in a previous work, so our results predict some differences
      between the reactivities of both compounds.

PMID- 29168766
TI  - Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In
      Vivo Lethal Dose Assay.
AB  - Scorpion stings are the main cause of human envenomation in Brazil and, for the
      treatment of victims, the World Health Organization (WHO) recommends the use of
      antivenoms. The first step to achieve effective antivenom is to use a good
      quality venom pool and to evaluate it, with LD50 determination as the most
      accepted procedure. It is, however, time-consuming and requires advanced
      technical training. Further, there are significant ethical concerns regarding the
      number of animals required for testing. Hence, we investigated the correspondence
      between LD50 results, in vitro assays, and a strong correlation with proteolytic
      activity levels was observed, showing, remarkably, that proteases are potential
      toxicity markers for Tityus serrulatus venom. The comparison of reversed-phase
      chromatographic profiles also has a potential application in venoms' quality
      control, as there were fewer neurotoxins detected in the venom with high LD50
      value. These results were confirmed by mass spectrometry analysis. Therefore,
      these methods could precede the LD50 assay to evaluate the venom excellence by
      discriminating-and discarding-poor-quality batches, and, consequently, with a
      positive impact on the number of animals used. Notably, proposed assays are fast
      and inexpensive, being technically and economically feasible in Tityus serrulatus
      venom quality control to produce effective antivenoms.

PMID- 29168768
TI  - Ionic Liquid-Mediated Homogeneous Esterification of Cinnamic Anhydride to Xylans.
AB  - A new functional biopolymer was synthesized through an ionic liquid-mediated
      homogeneous grafting of cinnamic anhydride to xylans. The ionic liquid used was 1
      allyl-3-methylimidazolium chloride (AMIMCl) ionic liquid. Xylans with degrees of
      substitution (DS) between 0.11 and 0.57 were accessible in a completely
      homogeneous system by changing catalysts (NaOH, KOH and LiOH), time, reaction
      temperature, and cinnamic anhydride/xylan molar ratio. The chemical structure and
      the thermal stability of the derivatives were characterized by Fourier transform
      infrared spectroscopy (FT-IR), 13C-NMR spectroscopy, and thermogravimetry. The
      thermal stability of the derivatives was reduced compared with the original
      xylan. Possible applications of the cinnamic anhydride-acylated xylan derivatives
      include wet-end papermaking, organic-inorganic composite films, and hydrogels.

PMID- 29168767
TI  - Long Non-Coding RNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma:
      Regulation, Functions, and Underlying Mechanisms.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third
      leading cause of cancer death in the world. Hepatitis B virus (HBV) and its X
      gene-encoded protein (HBx) play important roles in the progression of HCC.
      Although long non-coding RNAs (lncRNAs) cannot encode proteins, growing evidence
      indicates that they play essential roles in HCC progression, and contribute to
      cell proliferation, invasion and metastasis, autophagy, and apoptosis by
      targeting a large number of pivotal protein-coding genes, miRNAs, and signaling
      pathways. In this review, we briefly outline recent findings of differentially
      expressed lncRNAs in HBV-related HCC, with particular focus on several key
      lncRNAs, and discuss their regulation by HBV/HBx, their functions, and their
      underlying molecular mechanisms in the progression of HCC.

PMID- 29168769
TI  - Early Detection of the Initiation of Sit-to-Stand Posture Transitions Using
      Orthosis-Mounted Sensors.
AB  - Assistance during sit-to-stand (SiSt) transitions for frail elderly may be
      provided by powered orthotic devices. The control of the powered orthosis may be
      performed by the means of electromyography (EMG), which requires direct contact
      of measurement electrodes to the skin. The purpose of this study was to determine
      if a non-EMG-based method that uses inertial sensors placed at different
      positions on the orthosis, and a lightweight pattern recognition algorithm may
      accurately identify SiSt transitions without false positives. A novel method is
      proposed to eliminate false positives based on a two-stage design: stage one
      detects the sitting posture; stage two recognizes the initiation of a SiSt
      transition from a sitting position. The method was validated using data from 10
      participants who performed 34 different activities and posture transitions.
      Features were obtained from the sensor signals and then combined into lagged
      epochs. A reduced number of features was selected using a minimum-redundancy
      maximum-relevance (mRMR) algorithm and forward feature selection. To obtain a
      recognition model with low computational complexity, we compared the use of an
      extreme learning machine (ELM) and multilayer perceptron (MLP) for both stages of
      the recognition algorithm. Both classifiers were able to accurately identify all
      posture transitions with no false positives. The average detection time was 0.19
      +/- 0.33 s for ELM and 0.13 +/- 0.32 s for MLP. The MLP classifier exhibited less
      time complexity in the recognition phase compared to ELM. However, the ELM
      classifier presented lower computational demands in the training phase. Results
      demonstrated that the proposed algorithm could potentially be adopted to control
      a powered orthosis.

PMID- 29168770
TI  - Lanthanide-Doped Nanoparticles for Diagnostic Sensing.
AB  - Lanthanide-doped nanoparticles exhibit unique optical properties, such as a long
      luminescence lifetime (up to several milliseconds), sharp emission peaks, and
      upconversion luminescence over the range of wavelengths from near-infrared to
      visible. Exploiting these optical properties, lanthanide-doped nanoparticles have
      been widely utilized for cellular and small animal imaging with the absence of
      background autofluorescence. In addition, these nanoparticles have advantages of
      high signal-to-noise ratio for highly sensitive and selective diagnostic
      detection. In this review, we summarize and discuss recent progress in the
      development of highly sensitive diagnostic methods using lanthanide-doped
      nanoparticles. Combined with a smartphone, portable luminescence detecting
      platforms could be widely applied in point-of-care tests.

PMID- 29168771
TI  - Iron-Based Nanomaterials/Graphene Composites for Advanced Electrochemical
      Sensors.
AB  - Iron oxide nanostructures (IONs) in combination with graphene or its derivatives
      e.g., graphene oxide and reduced graphene oxide-hold great promise toward
      engineering of efficient nanocomposites for enhancing the performance of advanced
      devices in many applicative fields. Due to the peculiar electrical and
      electrocatalytic properties displayed by composite structures in nanoscale
      dimensions, increasing efforts have been directed in recent years toward
      tailoring the properties of IONs-graphene based nanocomposites for developing
      more efficient electrochemical sensors. In the present feature paper, we first
      reviewed the various routes for synthesizing IONs-graphene nanostructures,
      highlighting advantages, disadvantages and the key synthesis parameters for each
      method. Then, a comprehensive discussion is presented in the case of application
      of IONs-graphene based composites in electrochemical sensors for the
      determination of various kinds of (bio)chemical substances.

PMID- 29168772
TI  - A Survey of Recent Advances in Particle Filters and Remaining Challenges for
      Multitarget Tracking.
AB  - We review some advances of the particle filtering (PF) algorithm that have been
      achieved in the last decade in the context of target tracking, with regard to
      either a single target or multiple targets in the presence of false or missing
      data. The first part of our review is on remarkable achievements that have been
      made for the single-target PF from several aspects including importance proposal,
      computing efficiency, particle degeneracy/impoverishment and constrained/multi
      modal systems. The second part of our review is on analyzing the intractable
      challenges raised within the general multitarget (multi-sensor) tracking due to
      random target birth and termination, false alarm, misdetection, measurement-to
      track (M2T) uncertainty and track uncertainty. The mainstream multitarget PF
      approaches consist of two main classes, one based on M2T association approaches
      and the other not such as the finite set statistics-based PF. In either case,
      significant challenges remain due to unknown tracking scenarios and integrated
      tracking management.

PMID- 29168773
TI  - Verification of Non-Invasive Blood Glucose Measurement Method Based on Pulse Wave
      Signal Detected by FBG Sensor System.
AB  - This paper describes and verifies a non-invasive blood glucose measurement method
      using a fiber Bragg grating (FBG) sensor system. The FBG sensor is installed on
      the radial artery, and the strain (pulse wave) that is propagated from the
      heartbeat is measured. The measured pulse wave signal was used as a collection of
      feature vectors for multivariate analysis aiming to determine the blood glucose
      level. The time axis of the pulse wave signal was normalized by two signal
      processing methods: the shortest-time-cut process and 1-s-normalization process.
      The measurement accuracy of the calculated blood glucose level was compared with
      the accuracy of these signal processing methods. It was impossible to calculate a
      blood glucose level exceeding 200 mg/dL in the calibration curve that was
      constructed by the shortest-time-cut process. In the 1-s-normalization process,
      the measurement accuracy of the blood glucose level was improved, and a blood
      glucose level exceeding 200 mg/dL could be calculated. By verifying the loading
      vector of each calibration curve to calculate the blood glucose level with a high
      measurement accuracy, we found the gradient of the peak of the pulse wave at the
      acceleration plethysmogram greatly affected.

PMID- 29168775
TI  - Wearable Stretch Sensors for Motion Measurement of the Wrist Joint Based on
      Dielectric Elastomers.
AB  - Motion capture of the human body potentially holds great significance for
      exoskeleton robots, human-computer interaction, sports analysis, rehabilitation
      research, and many other areas. Dielectric elastomer sensors (DESs) are excellent
      candidates for wearable human motion capture systems because of their intrinsic
      characteristics of softness, light weight, and compliance. In this paper, DESs
      were applied to measure all component motions of the wrist joints. Five sensors
      were mounted to different positions on the wrist, and each one is for one
      component motion. To find the best position to mount the sensors, the
      distribution of the muscles is analyzed. Even so, the component motions and the
      deformation of the sensors are coupled; therefore, a decoupling method was
      developed. By the decoupling algorithm, all component motions can be measured
      with a precision of 5 degrees , which meets the requirements of general motion
      capture systems.

PMID- 29168776
TI  - Enhancement of Osteoblastic-Like Cell Activity by Glow Discharge Plasma Surface
      Modified Hydroxyapatite/beta-Tricalcium Phosphate Bone Substitute.
AB  - Glow discharge plasma (GDP) treatments of biomaterials, such as
      hydroxyapatite/beta-tricalcium phosphate (HA/beta-TCP) composites, produce
      surfaces with fewer contaminants and may facilitate cell attachment and enhance
      bone regeneration. Thus, in this study we used argon glow discharge plasma (Ar
      GDP) treatments to modify HA/beta-TCP particle surfaces and investigated the
      physical and chemical properties of the resulting particles (HA/beta-TCP + Ar
      GDP). The HA/beta-TCP particles were treated with GDP for 15 min in argon gas at
      room temperature under the following conditions: power: 80 W; frequency: 13.56
      MHz; pressure: 100 mTorr. Scanning electron microscope (SEM) observations showed
      similar rough surfaces of HA/beta-TCP + Ar-GDP HA/beta-TCP particles, and energy
      dispersive spectrometry analyses showed that HA/beta-TCP surfaces had more
      contaminants than HA/beta-TCP + Ar-GDP surfaces. Ca/P mole ratios in HA/beta-TCP
      and HA/beta-TCP + Ar-GDP were 1.34 and 1.58, respectively. Both biomaterials
      presented maximal intensities of X-ray diffraction patterns at 27 degrees  with
      600 a.u. At 25 degrees  and 40 degrees , HA/beta-TCP + Ar-GDP and HA/beta-TCP
      particles had peaks of 200 a.u., which are similar to XRD intensities of human
      bone. In subsequent comparisons, MG-63 cell viability and differentiation into
      osteoblast-like cells were assessed on HA/beta-TCP and HA/beta-TCP + Ar-GDP
      surfaces, and Ar-GDP treatments led to improved cell growth and alkaline
      phosphatase activities. The present data indicate that GDP surface treatment
      modified HA/beta-TCP surfaces by eliminating contaminants, and the resulting
      graft material enhanced bone regeneration.

PMID- 29168777
TI  - Association of Emotional Labor and Occupational Stressors with Depressive
      Symptoms among Women Sales Workers at a Clothing Shopping Mall in the Republic of
      Korea: A Cross-Sectional Study.
AB  - In the distribution service industry, sales people often experience multiple
      occupational stressors such as excessive emotional labor, workplace mistreatment,
      and job insecurity. The present study aimed to explore the associations of these
      stressors with depressive symptoms among women sales workers at a clothing
      shopping mall in Korea. A cross sectional study was conducted on 583 women who
      consist of clothing sales workers and manual workers using a structured
      questionnaire to assess demographic factors, occupational stressors, and
      depressive symptoms. Multiple regression analyses were performed to explore the
      association of these stressors with depressive symptoms. Scores for job stress
      subscales such as job demand, job control, and job insecurity were higher among
      sales workers than among manual workers (p < 0.01). The multiple regression
      analysis revealed the association between occupation and depressive symptoms
      after controlling for age, educational level, cohabiting status, and occupational
      stressors (sbeta = 0.08, p = 0.04). A significant interaction effect between
      occupation and social support was also observed in this model (sbeta = -0.09, p =
      0.02). The multiple regression analysis stratified by occupation showed that job
      demand, job insecurity, and workplace mistreatment were significantly associated
      with depressive symptoms in both occupations (p < 0.05), although the strength of
      statistical associations were slightly different. We found negative associations
      of social support (sbeta = -0.22, p < 0.01) and emotional effort (sbeta = -0.17,
      p < 0.01) with depressive symptoms in another multiple regression model for sales
      workers. Emotional dissonance (sbeta = 0.23, p < 0.01) showed positive
      association with depressive symptoms in this model. The result of this study
      indicated that reducing occupational stressors would be effective for women sales
      workers to prevent depressive symptoms. In particular, promoting social support
      could be the most effective way to promote women sales workers' mental health.

PMID- 29168778
TI  - Statistical Analysis of the Random Telegraph Noise in a 1.1 MUm Pixel, 8.3 MP
      CMOS Image Sensor Using On-Chip Time Constant Extraction Method.
AB  - A study of the random telegraph noise (RTN) of a 1.1 MUm pitch, 8.3 Mpixel CMOS
      image sensor (CIS) fabricated in a 45 nm backside-illumination (BSI) technology
      is presented in this paper. A noise decomposition scheme is used to pinpoint the
      noise source. The long tail of the random noise (RN) distribution is directly
      linked to the RTN from the pixel source follower (SF). The full 8.3 Mpixels are
      classified into four categories according to the observed RTN histogram peaks. A
      theoretical formula describing the RTN as a function of the time difference
      between the two phases of the correlated double sampling (CDS) is derived and
      validated by measured data. An on-chip time constant extraction method is
      developed and applied to the RTN analysis. The effects of readout circuit
      bandwidth on the settling ratios of the RTN histograms are investigated and
      successfully accounted for in a simulation using a RTN behavior model.

PMID- 29168774
TI  - Carotenoids from Marine Organisms: Biological Functions and Industrial
      Applications.
AB  - As is the case for terrestrial organisms, carotenoids represent the most common
      group of pigments in marine environments. They are generally biosynthesized by
      all autotrophic marine organisms, such as bacteria and archaea, algae and fungi.
      Some heterotrophic organisms also contain carotenoids probably accumulated from
      food or partly modified through metabolic reactions. These natural pigments are
      divided into two chemical classes: carotenes (such as lycopene and alpha- and
      beta-carotene) that are composed of hydrogen and carbon; xanthophylls (such as
      astaxanthin, fucoxanthin and lutein), which are constituted by hydrogen, carbon
      and oxygen. Carotenoids, as antioxidant compounds, assume a key role in the
      protection of cells. In fact, quenching of singlet oxygen, light capture and
      photosynthesis protection are the most relevant biological functions of
      carotenoids. The present review aims at describing (i) the biological functions
      of carotenoids and their benefits for human health, (ii) the most common
      carotenoids from marine organisms and (iii) carotenoids having large success in
      pharmaceutical, nutraceutical and cosmeceutical industries, highlighting the
      scientific progress in marine species cultivation for natural pigments
      production.

PMID- 29168779
TI  - Factors Effecting the Total Volatile Organic Compound (TVOC) Concentrations in
      Slovak Households.
AB  - Thirty five Slovak households were selected for an investigation of indoor
      environmental quality. Measuring of indoor air physical and chemical factors and
      a questionnaire survey was performed during May 2017. The range of permissible
      operative temperature was not met in 11% of objects. Relative humidity met the
      legislative requirements in all monitored homes. Concentrations of total volatile
      organic compounds (TVOCs) were significantly higher in the apartments than in the
      family houses. The average TVOC levels in the apartments and family houses were
      519.7 ug/m3 and 330.2 ug/m3, respectively. Statistical analysis confirmed the
      effect of indoor air temperature, relative humidity and particulate matter (PM0.5
      and PM1) on the levels of TVOCs. Higher TVOC levels were observed also in homes
      where it is not a common practice to open windows during cleaning activities.
      Other factors that had a statistically significant effect on concentrations of
      volatile organic compounds were heating type, attached garage, location of the
      apartment within residential building (the floor), as well as number of
      occupants. Higher TVOC concentrations were observed in indoor than outdoor
      environment, while further analysis showed the significant impact of indoor
      emission sources on the level of these compounds in buildings. The questionnaire
      study showed a discrepancy between objective measurement and subjective
      assessment in the household environment, and pointed to insufficient public
      awareness about volatile organic compounds (VOCs).

PMID- 29168780
TI  - Factors Associated with Dental Caries in Primary Dentition in a Non-Fluoridated
      Rural Community of New South Wales, Australia.
AB  - Dental caries persists as one of the most prevalent chronic diseases among
      children worldwide. This study aims to determine factors that influence dental
      caries in primary dentition among primary school children residing in the rural
      non-fluoridated community of Lithgow, New South Wales, Australia. A total of 495
      children aged 5-10 years old from all the six primary schools in Lithgow were
      approached to participate in a cross-sectional survey prior to implementation of
      water fluoridation in 2014. Following parental consent, children were clinically
      examined for caries in their primary teeth, and parents were requested to
      complete a questionnaire on previous fluoride exposure, diet and relevant socio
      demographic characteristics that influence oral health. Multiple logistic
      regression analysis was employed to examine the independent risk factors of
      primary dentition caries. Overall, 51 percent of children had dental caries in
      one or more teeth. In the multiple logistic regression analysis, child's age
      (Adjusted Odd's Ratio (AOR) = 1.30, 95% CI: 1.14-1.49) and mother's extraction
      history (AOR = 2.05, 95% CI: 1.40-3.00) were significantly associated with caries
      experience in the child's primary teeth. In addition, each serve of chocolate
      consumption was associated with 52 percent higher odds (AOR = 1.52, 95% CI: 1.19
      1.93) of primary dentition caries.

PMID- 29168782
TI  - The Preparation and Microstructure of Nanocrystal 3C-SiC/ZrO2 Bilayer Films.
AB  - The nanocrystal 3C-SiC/ZrO2 bilayer films that could be used as the protective
      coatings of zirconium alloy fuel cladding were prepared on a single-crystal Si
      substrate. The corresponding nanocrystal 3C-SiC film and nanocrystal ZrO2 film
      were also dividedly synthesized. The microstructure of nanocrystal films was
      analyzed by grazing incidence X-ray diffraction (GIXRD) and cross-sectional
      transmission electron microscopy (TEM). The 3C-SiC film with less than 30 nm
      crystal size was synthesized by Plasma Enhanced Chemical Vapor Deposition (PECVD)
      and annealing. The corresponding formation mechanism of some impurities in SiC
      film was analyzed and discussed. An amorphous Zr layer about 600 nm in width was
      first deposited by magnetron sputtering and then oxidized to form a nanocrystal
      ZrO2 layer during the annealing process. The interface characteristics of 3C
      SiC/ZrO2 bilayer films prepared by two different processes were obviously
      different. SiZr and SiO2 compounds were formed at the interface of 3C-SiC/ZrO2
      bilayer films. A corrosion test of 3C-SiC/ZrO2 bilayer films was conducted to
      qualitatively analyze the surface corrosion resistance and the binding force of
      the interface.

PMID- 29168783
TI  - Designing and Testing a UAV Mapping System for Agricultural Field Surveying.
AB  - A Light Detection and Ranging (LiDAR) sensor mounted on an Unmanned Aerial
      Vehicle (UAV) can map the overflown environment in point clouds. Mapped canopy
      heights allow for the estimation of crop biomass in agriculture. The work
      presented in this paper contributes to sensory UAV setup design for mapping and
      textual analysis of agricultural fields. LiDAR data are combined with data from
      Global Navigation Satellite System (GNSS) and Inertial Measurement Unit (IMU)
      sensors to conduct environment mapping for point clouds. The proposed method
      facilitates LiDAR recordings in an experimental winter wheat field. Crop height
      estimates ranging from 0.35-0.58 m are correlated to the applied nitrogen
      treatments of 0-300 kg N ha . The LiDAR point clouds are recorded, mapped, and
      analysed using the functionalities of the Robot Operating System (ROS) and the
      Point Cloud Library (PCL). Crop volume estimation is based on a voxel grid with a
      spatial resolution of 0.04 * 0.04 * 0.001 m. Two different flight patterns are
      evaluated at an altitude of 6 m to determine the impacts of the mapped LiDAR
      measurements on crop volume estimations.

PMID- 29168781
TI  - Structural Diversity and Biological Activities of the Cyclodipeptides from Fungi.
AB  - Cyclodipeptides, called 2,5-diketopiperazines (2,5-DKPs), are obtained by the
      condensation of two amino acids. Fungi have been considered to be a rich source
      of novel and bioactive cyclodipeptides. This review highlights the occurrence,
      structures and biological activities of the fungal cyclodipeptides with the
      literature covered up to July 2017. A total of 635 fungal cyclodipeptides
      belonging to the groups of tryptophan-proline, tryptophan-tryptophan, tryptophan
      Xaa, proline-Xaa, non-tryptophan-non-proline, and thio-analogs have been
      discussed and reviewed. They were mainly isolated from the genera of Aspergillus
      and Penicillium. More and more cyclodipeptides have been isolated from marine
      derived and plant endophytic fungi. Some of them were screened to have cytotoxic,
      phytotoxic, antimicrobial, insecticidal, vasodilator, radical scavenging,
      antioxidant, brine shrimp lethal, antiviral, nematicidal, antituberculosis, and
      enzyme-inhibitory activities to show their potential applications in agriculture,
      medicinal, and food industry.

PMID- 29168785
TI  - FTUC: A Flooding Tree Uneven Clustering Protocol for a Wireless Sensor Network.
AB  - Clustering is an efficient approach in a wireless sensor network (WSN) to reduce
      the energy consumption of nodes and to extend the lifetime of the network.
      Unfortunately, this approach requires that all cluster heads (CHs) transmit their
      data to the base station (BS), which gives rise to the long distance
      communications problem, and in multi-hop routing, the CHs near the BS have to
      forward data from other nodes that lead those CHs to die prematurely, creating
      the hot zones problem. Unequal clustering has been proposed to solve these
      problems. Most of the current algorithms elect CH only by considering their
      competition radius, leading to unevenly distributed cluster heads. Furthermore,
      global distances values are needed when calculating the competition radius, which
      is a tedious task in large networks. To face these problems, we propose a
      flooding tree uneven clustering protocol (FTUC) suited for large networks. Based
      on the construction of a tree type sub-network to calculate the minimum and
      maximum distances values of the network, we then apply the unequal cluster
      theory. We also introduce referenced position circles to evenly elect cluster
      heads. Therefore, cluster heads are elected depending on the node's residual
      energy and their distance to a referenced circle. FTUC builds the best inter
      cluster communications route by evaluating a cluster head cost function to find
      the best next hop to the BS. The simulation results show that the FTUC algorithm
      decreases the energy consumption of the nodes and balances the global energy
      consumption effectively, thus extending the lifetime of the network.

PMID- 29168784
TI  - Optimization of the Use of His6-OPH-Based Enzymatic Biocatalysts for the
      Destruction of Chlorpyrifos in Soil.
AB  - Applying enzymatic biocatalysts based on hexahistidine-containing
      organophosphorus hydrolase (His6-OPH) is suggested for the decomposition of
      chlorpyrifos, which is actively used in agriculture in many countries. The
      application conditions were optimized and the following techniques was suggested
      to ensure the highest efficiency of the enzyme: first, the soil is alkalinized
      with hydrated calcitic lime Ca(OH)2, then the enzyme is introduced into the soil
      at a concentration of 1000 U/kg soil. Non-equilibrium low temperature plasma
      (NELTP)-modified zeolite is used for immobilization of the relatively inexpensive
      polyelectrolyte complexes containing the enzyme His6-OPH and a polyanionic
      polymer: poly-l-glutamic acid (PLE50) or poly-l-aspartic acid (PLD50). The soil's
      humidity is then increased up to 60-80%, the top layer (10-30 cm) of soil is
      thoroughly stirred, and then exposed for 48-72 h. The suggested approach ensures
      100% destruction of the pesticide within 72 h in soils containing as much as 100
      mg/kg of chlorpyrifos. It was concluded that using this type of His6-OPH-based
      enzyme chemical can be the best approach for soils with relatively low humus
      concentrations, such as sandy and loam-sandy chestnut soils, as well as types of
      soil with increased alkalinity (pH 8.0-8.4). Such soils are often encountered in
      desert, desert-steppe, foothills, and subtropical regions where chlorpyrifos is
      actively used.

PMID- 29168787
TI  - FRED: Exergame to Prevent Dependence and Functional Deterioration Associated with
      Ageing. A Pilot Three-Week Randomized Controlled Clinical Trial.
AB  - Introduction: Frailty syndrome and advanced age may decrease the acceptance of
      illness and quality of life, and worsen patients' existing health conditions, as
      well as leading to an increase in health care expenses. Purpose: The purpose of
      this study is to reduce frailty risk via the use of a FRED game which has been
      expressly designed and put together for the study. Materials and methods: A total
      of 40 frail volunteers with a score of <10 points in the short physical
      performance battery (SPPB) took part in a feasibility study in order to validate
      the FRED game. Following randomisation, the study group (20 subjects) took part
      in nine sessions of 20 min each over a three-week period. The control group (19
      subjects) continued to lead their daily lives in the course of which they had no
      physical activity scheduled; Results: After three weeks and having taken part in
      nine physical activity sessions with the FRED game, 60% of subjects from the
      study group (12/20) obtained a score of >=10 points at the end of the study,
      i.e., less risk of evidencing frailty. This result proved to be statistically
      significant (p < 0.001). The degree of compliance with and adherence to the game
      was confirmed by 100% attendance of the sessions. Discussion: Our findings
      support the hypothesis that FRED, an ad hoc designed exergame, significantly
      reduced the presence and severity of frailty in a sample of sedentary elders,
      thus potentially modifying their risk profile. Conclusions: The FRED game is a
      tool that shows a 99% certain improvement in the degree of frailty in frail
      elderly subjects. The effectiveness of the design of ad hoc games in a certain
      pathology or population group is therefore evidenced.

PMID- 29168788
TI  - Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual
      Inhibitors.
AB  - Microtubule-targeting agents are widely used as clinical drugs in the treatment
      of cancer. However, some kinase inhibitors can also disrupt microtubule
      organization by directly binding to tubulin. These unexpected effects may result
      in a plethora of harmful events and/or a misinterpretation of the experimental
      results. Thus, further studies are needed to understand these dual inhibitors. In
      this review, I discuss the roles of dual inhibitors of kinase activity and
      microtubule function as well as describe the properties underlining their dual
      roles. Since both kinase and microtubule inhibitors cause cell toxicity and cell
      cycle arrest, it is difficult to determine which inhibitor is responsible for
      each phenotype. A discrimination of cell cycle arrest at G0/G1 or G2/M and/or
      image analyses of cellular phenotype may eventually lead to new insights on drug
      duality. Because of the indispensable roles of microtubules in mitosis and
      vesicle transport, I propose a simple and easy method to identify microtubule
      depolymerizing compounds.

PMID- 29168786
TI  - Effects of Commonly Used Pesticides in China on the Mitochondria and Ubiquitin
      Proteasome System in Parkinson's Disease.
AB  - Evidence continues to accumulate that pesticides are the leading candidates of
      environmental toxins that may contribute to the pathogenesis of Parkinson's
      disease. The mechanisms, however, remain largely unclear. According to
      epidemiological studies, we selected nine representative pesticides (paraquat,
      rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate, tebufenpyrad,
      trichlorphon and carbaryl) which are commonly used in China and detected the
      effects of the pesticides on mitochondria and ubiquitin-proteasome system (UPS)
      function. Our results reveal that all the nine studied pesticides induce
      morphological changes of mitochondria at low concentrations. Paraquat, rotenone,
      chlorpyrifos, pendimethalin, endosulfan, fenpyroximate and tebufenpyrad induced
      mitochondria fragmentation. Furthermore, some of them (paraquat, rotenone,
      chlorpyrifos, fenpyroximate and tebufenpyrad) caused a significant dose-dependent
      decrease of intracellular ATP. Interestingly, these pesticides which induce
      mitochondria dysfunction also inhibit 26S and 20S proteasome activity. However,
      two out of the nine pesticides, namely trichlorphon and carbaryl, were found not
      to cause mitochondrial fragmentation or functional damage, nor inhibit the
      activity of the proteasome, which provides significant guidance for selection of
      pesticides in China. Moreover, our results demonstrate a potential link between
      inhibition of mitochondria and the UPS, and pesticide-induced Parkinsonism.

PMID- 29168789
TI  - Lead Emissions and Population Vulnerability in the Detroit (Michigan, USA)
      Metropolitan Area, 2006-2013: A Spatial and Temporal Analysis.
AB  - Objective: The purpose of this research is to geographically model airborne lead
      emission concentrations and total lead deposition in the Detroit Metropolitan
      Area (DMA) from 2006 to 2013. Further, this study characterizes the racial and
      socioeconomic composition of recipient neighborhoods and estimates the potential
      for IQ (Intelligence Quotient) loss of children residing there. Methods: Lead
      emissions were modeled from emitting facilities in the DMA using AERMOD (American
      Meteorological Society/Environmental Protection Agency Regulatory Model).
      Multilevel modeling was used to estimate local racial residential segregation,
      controlling for poverty. Global Moran's I bivariate spatial autocorrelation
      statistics were used to assess modeled emissions with increasing segregation.
      Results: Lead emitting facilities were primarily located in, and moving to,
      highly black segregated neighborhoods regardless of poverty levels-a phenomenon
      known as environmental injustice. The findings from this research showed three
      years of elevated airborne emission concentrations in these neighborhoods to
      equate to a predicted 1.0 to 3.0 reduction in IQ points for children living
      there. Across the DMA there are many areas where annual lead deposition was
      substantially higher than recommended for aquatic (rivers, lakes, etc.) and
      terrestrial (forests, dunes, etc.) ecosystems. These lead levels result in
      decreased reproductive and growth rates in plants and animals, and neurological
      deficits in vertebrates. Conclusions: This lead-hazard and neighborhood context
      assessment will inform future childhood lead exposure studies and potential
      health consequences in the DMA.

PMID- 29168790
TI  - Coxiella burnetii Lipopolysaccharide: What Do We Know?
AB  - A small gram-negative bacterium, Coxiella burnetii (C. burnetii), is responsible
      for a zoonosis called Q fever. C. burnetii is an intracellular bacterium that can
      survive inside microbicidal cells like monocytes and macrophages by hijacking
      several functions of the immune system. Among several virulence factors, the
      lipopolysaccharide (LPS) of C. burnetii is one of the major factors involved in
      this immune hijacking because of its atypical composition and structure. Thus,
      the aim of this mini-review is to summarize the repressive effects of C. burnetii
      LPS on the antibacterial immunity of cells.

PMID- 29168791
TI  - Administration of Protocatechuic Acid Reduces Traumatic Brain Injury-Induced
      Neuronal Death.
AB  - Protocatechuic acid (PCA) was first purified from green tea and has shown
      numerous biological activities, including anti-apoptotic, anti-inflammatory, and
      anti-atherosclerotic effects. The effect of PCA on traumatic brain injury (TBI)
      induced neuronal death has not previously been evaluated. TBI is defined as
      damage to the brain resulting from external mechanical force, such as rapid
      acceleration or deceleration, impact, blast waves, or penetration by a
      projectile. TBI causes neuronal death in the hippocampus and cerebral cortex. The
      present study aimed to evaluate the therapeutic potential of PCA on TBI-induced
      neuronal death. Here, TBI was induced by a controlled cortical impact model using
      rats. PCA (30 mg/kg) was injected into the intraperitoneal (ip) space immediately
      after TBI. Neuronal death was evaluated with Fluoro Jade-B (FJB) staining at 24 h
      after TBI. Oxidative injury was detected by 4-hydroxy-2-nonenal (4HNE),
      glutathione (GSH) concentration was analyzed by glutathione adduct with N
      ethylmaleimide (GS-NEM) staining at 24 h after TBI, and microglial activation in
      the hippocampus was detected by CD11b immunohistochemistry at one week after TBI.
      We found that the proportion of degenerating neurons, oxidative injury, GSH
      depletion, and microglia activation in the hippocampus and cortex were all
      reduced by PCA treatment following TBI. Therefore, our study suggests that PCA
      may have therapeutic potential in preventing TBI-induced neuronal death.

PMID- 29168792
TI  - Zinc Signal in Brain Diseases.
AB  - The divalent cation zinc is an integral requirement for optimal cellular
      processes, whereby it contributes to the function of over 300 enzymes, regulates
      intracellular signal transduction, and contributes to efficient synaptic
      transmission in the central nervous system. Given the critical role of zinc in a
      breadth of cellular processes, its cellular distribution and local tissue level
      concentrations remain tightly regulated via a series of proteins, primarily
      including zinc transporter and zinc import proteins. A loss of function of these
      regulatory pathways, or dietary alterations that result in a change in zinc
      homeostasis in the brain, can all lead to a myriad of pathological conditions
      with both acute and chronic effects on function. This review aims to highlight
      the role of zinc signaling in the central nervous system, where it may
      precipitate or potentiate diverse issues such as age-related cognitive decline,
      depression, Alzheimer's disease or negative outcomes following brain injury.

PMID- 29168793
TI  - Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling
      Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates
      and Their Quaternary Ammonium Salts.
AB  - Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4
      [(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were
      synthesized. The final step of synthesis of quaternary ammonium salts was carried
      out by microwave-assisted synthesis. Software-calculated data provided the
      background needed to compare fifteen new resulting compounds by their
      physicochemical properties. The acid dissociation constant (pKa) and
      lipophilicity index (log P) of tertiary amines were determined; while quaternary
      ammonium salts were characterized by software-calculated lipophilicity index and
      surface tension. Biological evaluation aimed at testing acetylcholinesterase and
      butyrylcholinesterase-inhibiting activity of synthesized compounds. A possible
      mechanism of action of these compounds was determined by molecular modelling
      study using combined techniques of docking; molecular dynamics simulations and
      quantum mechanics calculations.

PMID- 29168794
TI  - In Vitro Evaluation of PCL and P(3HB) as Coating Materials for Selective Laser
      Melted Porous Titanium Implants.
AB  - Titanium is widely used as a bone implant material due to its biocompatibility
      and high resilience. Since its Young's modulus differs from bone tissue, the
      resulting "stress shielding" could lead to scaffold loosening. However, by using
      a scaffold-shaped geometry, the Young's modulus can be adjusted. Also, a porous
      geometry enables vascularisation and bone ingrowth inside the implant itself.
      Additionally, growth factors can improve these effects. In order to create a
      deposit and release system for these factors, the titanium scaffolds could be
      coated with degradable polymers. Therefore, in the present study, synthetic poly
      epsilon-caprolactone (PCL) and the biopolymer poly(3-hydroxybutyrate) (P(3HB))
      were tested for coating efficiency, cell adhesion, and biocompatibility to find a
      suitable coating material. The underlying scaffold was created from titanium by
      Selective Laser Melting (SLM) and coated with PCL or P(3HB) via dip coating. To
      test the biocompatibility, Live Cell Imaging (LCI) as well as vitality and
      proliferation assays were performed. In addition, cell adhesion forces were
      detected via Single Cell Force Spectroscopy, while the coating efficiency was
      observed using environmental scanning electron microscopy (ESEM) and energy
      dispersive X-ray (EDX) analyses. Regarding the coating efficiency, PCL showed
      higher values in comparison to P(3HB). Vitality assays revealed decent vitality
      values for both polymers, while values for PCL were significantly lower than
      those for blank titanium. No significant differences could be observed between
      PCL and P(3HB) in proliferation and cell adhesion studies. Although LCI
      observations revealed decreasing values in cell number and populated area over
      time on both polymer-coated scaffolds, these outcomes could be explained by the
      possibility of coating diluent residues accumulating in the culture medium.
      Overall, both polymers fulfill the requirements regarding biocompatibility.
      Nonetheless, since only PCL coating ensured the maintenance of the porous implant
      structure, it is preferable to be used as a coating material for creating a
      deposit and release system for growth factors.

PMID- 29168795
TI  - Antipsychotic Polypharmacy among Children and Young Adults in Office-Based or
      Hospital Outpatient Department Settings.
AB  - The purpose of the study was three-fold: (1) to estimate the national trends in
      antipsychotic (AP) polypharmacy among 6- to 24-year-old patients in the U.S.; (2)
      to identify frequently used AP agents and mental disorder diagnoses related to AP
      polypharmacy; and (3) to assess the strength of association between AP
      polypharmacy and patient/provider characteristics. We used publicly available
      ambulatory health care datasets to evaluate AP polypharmacy in office-based or
      hospital outpatient department settings to conduct a cross-sectional study.
      First, national visit rates between 2007 and 2011 were estimated using sampling
      weights. Second, common diagnoses and drugs used in AP polypharmacy were
      identified. Third, a multivariate logistic regression model was developed to
      assess the strength of association between AP polypharmacy and patient and
      provider characteristics. Between 2007 and 2011, approximately 2% of office-based
      or hospital outpatient department visits made by 6- to 24-year-old patients
      included one or more AP prescriptions. Of these visits, 5% were classified as AP
      polypharmacy. The most common combination of AP polypharmacy was to use two or
      more second-generation APs. Also, bipolar disorder and schizophrenia were the two
      most frequent primary mental disorder diagnoses among AP polypharmacy visits. The
      factors associated with AP polypharmacy were: older age (young adults), black,
      having one or more non-AP prescriptions, and having schizophrenia or ADHD.

PMID- 29168796
TI  - The Effect of Eu Doping on Microstructure, Morphology and Methanal-Sensing
      Performance of Highly Ordered SnO2 Nanorods Array.
AB  - Layered Eu-doped SnO2 ordered nanoarrays constructed by nanorods with 10 nm
      diameters and several hundred nanometers length were synthesized by a substrate
      free hydrothermal route using alcohol and water mixed solvent of sodium stannate
      and sodium hydroxide at 200  degrees C. The Eu dopant acted as a crystal growth
      inhibitor to prevent the SnO2 nanorods growth up, resulting in tenuous SnO2
      nanorods ordered arrays. The X-ray diffraction (XRD) revealed the tetragonal
      rutile-type structure with a systematic average size reduction and unit cell
      volume tumescence, while enhancing the residual strain as the Eu-doped content
      increases. The surface defects that were caused by the incorporation of Eu ions
      within the surface oxide matrix were observed by high-resolution transmission
      electron microscope (HRTEM). The results of the response properties of sensors
      based on the different levels of Eu-doped SnO2 layered nanoarrays demonstrated
      that the 0.5 at % Eu-doped SnO2 layered nanorods arrays exhibited an excellent
      sensing response to methanal at 278  degrees C. The reasons of the enhanced
      sensing performance were discussed from the complicated defect surface structure,
      the large specific surface area, and the excellent catalytic properties of Eu
      dopant.

PMID- 29168798
TI  - Removal of Ciprofloxacin from Aqueous Solutions Using Pillared Clays.
AB  - Emerging contaminants in the environment have caused enormous concern in the last
      few decades, and among them, antibiotics have received special attention. On the
      other hand, adsorption has shown to be a useful, low-cost, and eco-friendly
      method for the removal of this type of contaminants from water. This work is
      focused on the study of ciprofloxacin (CPX) removal from water by adsorption on
      pillared clays (PILC) under basic pH conditions, where CPX is in its anionic form
      (CPX-). Four different materials were synthetized, characterized, and studied as
      adsorbents of CPX (Al-, Fe-, Si-, and Zr-PILC). The highest CPX adsorption
      capacities of 100.6 and 122.1 mg g-1 were obtained for the Si- and Fe-PILC
      (respectively), and can be related to the porous structure of the PILCs. The
      suggested adsorption mechanism involves inner-sphere complexes formation as well
      as van der Waals interactions between CPX- and the available adsorption sites on
      the PILC surfaces.

PMID- 29168799
TI  - Modulation of Cytochrome P450, P-glycoprotein and Pregnane X Receptor by Selected
      Antimalarial Herbs-Implication for Herb-Drug Interaction.
AB  - Seven medicinal plants popularly used for treating malaria in West Africa were
      selected to assess herb-drug interaction potential through a series of in vitro
      methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the
      recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and
      CYP3A4 to assess the effect of the methanolic extracts on the metabolic activity
      of CYPs. Secondly, the inhibitory effect of the extracts was evaluated on P
      glycoproteins (P-gp) using calcein-AM, a fluorescent substrate, in MDCK-II and
      hMDR1-MDCK-II cells. The inhibition of P-gp activity was determined as a
      reflection of increase in calcein-AM uptake. Additionally, the enzyme induction
      potential of the extracts was assessed through the modulation of PXR activity in
      HepG2 cells transiently transfected with pSG5-PXR and PCR5 plasmid DNA.
      Significant inhibition of CYP activity (IC50 < 10 ug/mL) was observed with the
      following herbs: A. muricata [CYP2C9, 3A4 and CYP2D6]; M. indica [CYP2C9]; M.
      charantia [CYP2C9 and CYP2C19]; P. amarus [CYP2C19, CYP2C9 and CYP3A4]; T.
      diversifolia [CYP2C19 and CYP3A4]. Extracts of four herbs (P. amarus, M.
      charantia, T. diversifolia and A. muricata) exhibited significant inhibition of P
      gp with IC50 values (ug/mL) of 17 +/- 1, 16 +/- 0.4, 26 +/- 1, and 24 +/- 1,
      respectively. In addition, four herbs (A. mexicana, M. charantia, P. amarus and
      T. diversifolia) showed a >two-fold increase in induction in PXR activity. These
      findings suggest that these herbs may be capable of eliciting herb-drug
      interactions if consumed in high quantities with concomitant use of conventional
      therapies.

PMID- 29168797
TI  - Role of Vitamin E in the Treatment of Alzheimer's Disease: Evidence from Animal
      Models.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder representing the major
      cause of dementia. It is characterized by memory loss, and cognitive and
      behavioral decline. In particular, the hallmarks of the pathology are amyloid
      beta (Abeta) plaques and neurofibrillary tangles (NFTs), formed by aggregated
      hyperphosphorylated tau protein. Oxidative stress plays a main role in AD, and it
      is involved in initiation and progression of AD. It is well known that Abeta
      induced oxidative stress, promoting reactive oxygen species (ROS) production and
      consequently lipid peroxidation, protein oxidation, tau hyperphosphorylation,
      results in toxic effects on synapses and neurons. In turn, oxidative stress can
      increase Abeta production. For these reasons, the administration of an
      antioxidant therapy in AD patients was suggested. The term vitamin E includes
      different fat-soluble compounds, divided into tocopherols and tocotrienols, that
      possess antioxidant action. alpha-Tocopherol is the most studied, but some
      studies suggested that tocotrienols may have different health promoting
      capacities. In this review, we focused our attention on the effects of vitamin E
      supplementation in AD animal models and AD patients or older population.
      Experimental models showed that vitamin E supplementation, by decreasing
      oxidative stress, may be a good strategy to improve cognitive and memory
      deficits. Furthermore, the combination of vitamin E with other antioxidant or
      anti-inflammatory compounds may increase its efficacy. However, even if some
      trials have evidenced some benefits, the effects of vitamin E in AD patients are
      still under debate.

PMID- 29168800
TI  - The Effect of a Two-Stage Heat-Treatment on the Microstructural and Mechanical
      Properties of a Maraging Steel.
AB  - Maraging steels gain many of their beneficial properties from heat treatments
      which induce the precipitation of intermetallic compounds. We consider here a two
      stage heat-treatment, first involving austenitisation, followed by quenching to
      produce martensite and then an ageing treatment at a lower temperature to
      precipitation harden the martensite of a maraging steel. It is shown that with a
      suitable choice of the initial austenitisation temperature, the steel can be heat
      treated to produce enhanced toughness, strength and creep resistance. A
      combination of small angle neutron scattering, scanning electron microscopy,
      electron back-scattered diffraction, and atom probe tomography were used to
      relate the microstructural changes to mechanical properties. It is shown that
      such a combination of characterisation methods is necessary to quantify this
      complex alloy, and relate these microstructural changes to mechanical properties.
      It is concluded that a higher austenitisation temperature leads to a greater
      volume fraction of smaller Laves phase precipitates formed during ageing, which
      increase the strength and creep resistance but reduces toughness.

PMID- 29168801
TI  - The histone code reader Spin1 controls skeletal muscle development.
AB  - While several studies correlated increased expression of the histone code reader
      Spin1 with tumor formation or growth, little is known about physiological
      functions of the protein. We generated Spin1M5 mice with ablation of Spin1 in
      myoblast precursors using the Myf5-Cre deleter strain. Most Spin1M5 mice die
      shortly after birth displaying severe sarcomere disorganization and necrosis.
      Surviving Spin1M5 mice are growth-retarded and exhibit the most prominent defects
      in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of
      limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided
      evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle
      (SkM) functional networks. Determination of genome-wide chromatin occupancy in
      primary myoblast revealed direct Spin1 target genes and suggested that
      deregulated basic helix-loop-helix transcription factor networks account for
      developmental defects in Spin1M5 fetuses. Furthermore, correlating histological
      and transcriptome analyses, we show that aberrant expression of titin-associated
      proteins, abnormal glycogen metabolism, and neuromuscular junction defects
      contribute to SkM pathology in Spin1M5 mice. Together, we describe the first
      example of a histone code reader controlling SkM development in mice, which hints
      at Spin1 as a potential player in human SkM disease.

PMID- 29168802
TI  - Ligand-accelerated non-directed C-H functionalization of arenes.
AB  - The directed activation of carbon-hydrogen bonds (C-H) is important in the
      development of synthetically useful reactions, owing to the proximity-induced
      reactivity and selectivity that is enabled by coordinating functional groups.
      Palladium-catalysed non-directed C-H activation could potentially enable further
      useful reactions, because it can reach more distant sites and be applied to
      substrates that do not contain appropriate directing groups; however, its
      development has faced substantial challenges associated with the lack of
      sufficiently active palladium catalysts. Currently used palladium catalysts are
      reactive only with electron-rich arenes, unless an excess of arene is used, which
      limits synthetic applications. Here we report a 2-pyridone ligand that binds to
      palladium and accelerates non-directed C-H functionalization with arene as the
      limiting reagent. This protocol is compatible with a broad range of aromatic
      substrates and we demonstrate direct functionalization of advanced synthetic
      intermediates, drug molecules and natural products that cannot be used in
      excessive quantities. We also developed C-H olefination and carboxylation
      protocols, demonstrating the applicability of our methodology to other
      transformations. The site selectivity in these transformations is governed by a
      combination of steric and electronic effects, with the pyridone ligand enhancing
      the influence of sterics on the selectivity, thus providing complementary
      selectivity to directed C-H functionalization.

PMID- 29168803
TI  - Photonuclear reactions triggered by lightning discharge.
AB  - Lightning and thunderclouds are natural particle accelerators. Avalanches of
      relativistic runaway electrons, which develop in electric fields within
      thunderclouds, emit bremsstrahlung gamma-rays. These gamma-rays have been
      detected by ground-based observatories, by airborne detectors and as terrestrial
      gamma-ray flashes from space. The energy of the gamma-rays is sufficiently high
      that they can trigger atmospheric photonuclear reactions that produce neutrons
      and eventually positrons via beta+ decay of the unstable radioactive isotopes,
      most notably 13N, which is generated via 14N + gamma -> 13N + n, where gamma
      denotes a photon and n a neutron. However, this reaction has hitherto not been
      observed conclusively, despite increasing observational evidence of neutrons and
      positrons that are presumably derived from such reactions. Here we report ground
      based observations of neutron and positron signals after lightning. During a
      thunderstorm on 6 February 2017 in Japan, a gamma-ray flash with a duration of
      less than one millisecond was detected at our monitoring sites 0.5-1.7 kilometres
      away from the lightning. The subsequent gamma-ray afterglow subsided quickly,
      with an exponential decay constant of 40-60 milliseconds, and was followed by
      prolonged line emission at about 0.511 megaelectronvolts, which lasted for a
      minute. The observed decay timescale and spectral cutoff at about 10
      megaelectronvolts of the gamma-ray afterglow are well explained by de-excitation
      gamma-rays from nuclei excited by neutron capture. The centre energy of the
      prolonged line emission corresponds to electron-positron annihilation, providing
      conclusive evidence of positrons being produced after the lightning.

PMID- 29168804
TI  - Hydrogen-bearing iron peroxide and the origin of ultralow-velocity zones.
AB  - Ultralow-velocity zones (ULVZs) at Earth's core-mantle boundary region have
      important implications for the chemical composition and thermal structure of our
      planet, but their origin has long been debated. Hydrogen-bearing iron peroxide
      (FeO2Hx) in the pyrite-type crystal structure was recently found to be stable
      under the conditions of the lowermost mantle. Using high-pressure experiments and
      theoretical calculations, we find that iron peroxide with a varying amount of
      hydrogen has a high density and high Poisson ratio as well as extremely low sound
      velocities consistent with ULVZs. Here we also report a reaction between iron and
      water at 86 gigapascals and 2,200 kelvin that produces FeO2Hx. This would provide
      a mechanism for generating the observed volume occupied by ULVZs through the
      reaction of about one-tenth the mass of Earth's ocean water in subducted hydrous
      minerals with the effectively unlimited reservoir of iron in Earth's core. Unlike
      other candidates for the composition of ULVZs, FeO2Hx synthesized from the
      superoxidation of iron by water would not require an extra transportation
      mechanism to migrate to the core-mantle boundary. These dense FeO2Hx-rich domains
      would be expected to form directly in the core-mantle boundary region and their
      properties would provide an explanation for the many enigmatic seismic features
      that are observed in ULVZs.

PMID- 29168805
TI  - Re-evaluating evolution in the HIV reservoir.

PMID- 29168806
TI  - Photonic quantum state transfer between a cold atomic gas and a crystal.
AB  - Interfacing fundamentally different quantum systems is key to building future
      hybrid quantum networks. Such heterogeneous networks offer capabilities superior
      to those of their homogeneous counterparts, as they merge the individual
      advantages of disparate quantum nodes in a single network architecture. However,
      few investigations of optical hybrid interconnections have been carried out,
      owing to fundamental and technological challenges such as wavelength and
      bandwidth matching of the interfacing photons. Here we report optical quantum
      interconnection of two disparate matter quantum systems with photon storage
      capabilities. We show that a quantum state can be transferred faithfully between
      a cold atomic ensemble and a rare-earth-doped crystal by means of a single photon
      at 1,552  nanometre telecommunication wavelength, using cascaded quantum
      frequency conversion. We demonstrate that quantum correlations between a photon
      and a single collective spin excitation in the cold atomic ensemble can be
      transferred to the solid-state system. We also show that single-photon time-bin
      qubits generated in the cold atomic ensemble can be converted, stored and
      retrieved from the crystal with a conditional qubit fidelity of more than 85 per
      cent. Our results open up the prospect of optically connecting quantum nodes with
      different capabilities and represent an important step towards the realization of
      large-scale hybrid quantum networks.

PMID- 29168807
TI  - Lorenzo-Redondo et al. reply.

PMID- 29168808
TI  - Improved diagnostics fail to halt the rise of tuberculosis.

PMID- 29168810
TI  - Thunderous nuclear reactions.

PMID- 29168809
TI  - Childhood obesity: A growing concern.

PMID- 29168811
TI  - Fatty liver disease.

PMID- 29168812
TI  - You've got the power.

PMID- 29168813
TI  - Experimentalists and theorists need to talk.

PMID- 29168814
TI  - Machinery that guides immunity.

PMID- 29168816
TI  - Super-reactive catalyst for bond cleavage.

PMID- 29168817
TI  - The most popular genes in the human genome.

PMID- 29168818
TI  - Online software spots genetic errors in cancer papers.

PMID- 29168819
TI  - Trailblazer: When Marie Curie went to Brazil.

PMID- 29168820
TI  - Exoplanet find, oil pipeline and a gene-editing first.

PMID- 29168821
TI  - PhD jobs: Revamp funding structures.

PMID- 29168822
TI  - Giant telescope's mobile-phone 'dead zones' rile South African residents.

PMID- 29168823
TI  - PhD jobs: Explore posts abroad.

PMID- 29168824
TI  - Research health needs a dedicated group.

PMID- 29168825
TI  - Disease progression: Divergent paths.

PMID- 29168826
TI  -  Drug development: Sprint finish.

PMID- 29168827
TI  - Layered-up regulation in the developing brain.

PMID- 29168829
TI  - Neuroscience starts talking.

PMID- 29168828
TI  - Hungary rewards highly cited scientists with bonus grants.

PMID- 29168832
TI  - Diagnostics: Missing the point.

PMID- 29168833
TI  - Correction.

PMID- 29168835
TI  - Research in action.

PMID- 29168836
TI  - We can and must govern climate engineering.

PMID- 29168837
TI  - Exoplanet hunters rethink search for alien life.

PMID- 29168838
TI  - Politics: Don't put US-Cuban research at risk.

PMID- 29168839
TI  - PhD jobs: Support beyond academia.

PMID- 29168840
TI  - As climate talks end, it is time for action.

PMID- 29168841
TI  - Maximize the impacts of space science.

PMID- 29168842
TI  - Rewarding negative results keeps science on track.

PMID- 29168843
TI  - How T cells spot tumour cells.

PMID- 29168844
TI  - Plasmonic and photo-electrochemical enhancements of the AuAg@Au/RGO-C3N4
      nanocomposite for the detection of DA.
AB  - Plasmonic photocatalyst has attracted significant attention due to its valuable
      theoretical study and promising practical applications in solar cells, functional
      composites, and sensors. Herein, an interesting RGO-C3N4-supported AuAg core-Au
      shell (AuAg@Au) nanocomposite has been reported. Due to the surface plasmon
      resonance (SPR) of AuAg@Au and the accelarated electron transfer and separation
      of charge carriers induced by the fascinating RGO-C3N4 substrate, the newly
      generated AuAg@Au/RGO-C3N4 nanomaterials show a strong photo-electrochemical
      response under visible-light irradiation. The AuAg@Au/RGO-C3N4 photocatalyst
      demonstrated an excellent photo-electrochemical performance with a broad
      concentration linear range of 0.064-780.904 MUM and a low detection limit of
      0.022 MUM, high stability, and good selectivity when applied in the determination
      of dopamine (DA) under visible-light irradiation.

PMID- 29168845
TI  - An ionic liquid-magnetic graphene composite for magnet dispersive solid-phase
      extraction of triazine herbicides in surface water followed by high performance
      liquid chromatography.
AB  - A new ionic liquid-magnetic graphene (IL-MG) composite was used as the adsorbent
      in magnetic dispersive solid-phase extraction to rapidly extract and isolate
      triazine herbicides from surface water. IL-MG was synthesized by a simple and
      time-saving one-pot strategy where the synthesis of magnetic Fe3O4, the
      modification with an IL, and the reduction of graphene oxide to graphene were
      conducted at the same time. An IL was applied to enrich the interaction mechanism
      between IL-MG and analytes (pi-pi, hydrophobic interaction, and electrostatic
      interaction). Moreover, the IL and Fe3O4 nanoparticles acted as spacers,
      inserting between the layers of graphene to prevent the aggregation of graphene,
      which improved the adsorption ability because of the large specific surface area
      of IL-MG. The resultant IL-MG had hierarchical flake structures and showed a high
      adsorption capacity (8266.0-12 324.1 MUg g-1) toward triazine herbicides. Under
      suitable conditions, the linearity for triazine herbicides was achieved in the
      range of 0.55-500 ng mL-1 with a detection limit of 0.09-0.15 ng mL-1 and a
      quantitation limit of 0.31-0.51 ng mL-1, and the enrichment factor was 83-fold,
      which indicated that the proposed method could be successfully applied for the
      determination of triazine herbicides in surface water.

PMID- 29168846
TI  - Rapid, portable detection of endocrine disrupting chemicals through ligand
      nuclear hormone receptor interactions.
AB  - Endocrine disrupting chemicals (EDC) are structurally diverse compounds that can
      interact with nuclear hormone receptors, posing significant risk to human and
      ecological health. Unfortunately, many conventional biosensors have been too
      structure-specific, labor-intensive or laboratory-oriented to detect broad ranges
      of EDC effectively. Recently, several technological advances are providing more
      rapid, portable, and affordable detection of endocrine-disrupting activity
      through ligand-nuclear hormone receptor interactions. Here, we overview these
      recent advances applied to EDC biosensors - including cell lyophilization, cell
      immobilization, cell-free systems, smartphone-based signal detection, and
      improved competitive binding assays.

PMID- 29168847
TI  - An aptamer and functionalized nanoparticle-based strip biosensor for on-site
      detection of kanamycin in food samples.
AB  - A lateral flow strip biosensor for fast, sensitive, low-cost and on-site
      detection of kanamycin was developed by using kanamycin-specific aptamer-modified
      gold nanoparticles (AuNPs-apt) as a probe and oligonucleotide DNA1-modified
      silver nanoparticles (AgNPs-DNA1) as a signal amplification element. Through the
      complementary sequences of DNA1 and the aptamer, the AgNP-DNA1-apt-AuNPs complex
      can be formed and further captured on the test zone of the strip, where a capture
      probe DNA2 complementary to the 3'-terminal of DNA1 was immobilized. In the
      presence of kanamycin, it can competitively bind to the aptamer, and then inhibit
      the formation of the complex and the accumulation of AuNPs on the test zone.
      AuNPs-apt can finally be captured on the control zone via the specific binding
      between biotin and streptavidin. The assay avoids multiple incubation and washing
      steps and can be completed within 10 min. By observing the color change of the
      test zone, a qualitative detection for kanamycin can be achieved by the naked
      eye, with the visual limit of 35 nM. Meanwhile, a linear detection range of 1-30
      nM with a low detection limit of 0.0778 nM for quantitative analysis can be
      achieved by using a scanning reader. The lateral flow strip biosensor exhibited
      high specificity and stability. Moreover, it was applied to detect kanamycin in
      various food samples, indicating its great potential in field testing.

PMID- 29168848
TI  - An etching based fluorescent probe for sensitive detection of hydrogen sulfide in
      cells.
AB  - Hydrogen sulfide (H2S) is one of the most crucial gas signaling agents that
      mediate many physiological and pathological processes. However, rapid high
      efficiency detection and imaging of H2S in living cells is very challenging.
      Herein we reported a simple fluorescent nanoprobe using FAM-DNA/AgNP
      nanocomposites for fast and sensitive H2S detection based on surface silver
      displacement. In contrast to the conventional principles for fluorescence turn-on
      analyte detection, the present work demonstrated a sensitive and selective AgNP
      based optosensor for the assay of H2S. Compared with the majority of the reported
      H2S probes, complex synthesis procedures and costly equipment are not involved in
      this assay.

PMID- 29168849
TI  - Highly effective target converting strategy for ultrasensitive electrochemical
      assay of Hg2.
AB  - An electrochemical sensing system based on a highly effective mercuric ion (Hg2+)
      converting strategy and rolling circle amplification (RCA) is developed for the
      ultrasensitive detection of Hg2+. The Hg2+ converting strategy is implemented
      based on Hg2+ specific recognition thymine-Hg2+-thymine (T-Hg2+-T)-induced DNA
      strand displacement. First, polystyrene magnetic microspheres coated by AuNPs
      (Au@PSC) as a magnetic separator were labeled with ssDNA D1 (thymine-rich) and
      S1/D2 DNA duplex (guanine-rich S1). In the presence of Hg2+ and long ssDNA D3
      (thymine-rich at the 5' end), the formation of a stable T-Hg2+-T structure
      between D2 and D3 pushes S1 out from the S1/D2 DNA duplex, realizing the
      conversion of input target Hg2+ into output S1. Thus, the total amount of output
      S1 is proportional to the amount of input Hg2+. Thereafter, the output S1 serves
      as the primer to perform RCA to obtain long guanine-rich ssDNA, which could be
      further hybridized with the capture DNA on the electrode surface. Subsequently,
      methylene blue (MB) as an electron mediator interacts with the ssDNA polymers via
      electrostatic binding to produce a detection signal. The electrochemical
      biosensor exhibits a wide linear range of 1 pM to 1 MUM with a low detection
      limit of 0.684 pM. Importantly, this sensor can be successfully applied in water
      samples with good accuracy and excellent recovery, which indicates its potential
      for Hg2+ detection in the environment.

PMID- 29168850
TI  - A tellurylsulfide bond-containing redox-responsive superparamagnetic nanogel with
      acid-responsiveness for efficient anticancer therapy.
AB  - A tellurylsulfide bond-containing biopolymer nanogel was first fabricated to
      achieve smart drug release. The reductive nanogel exhibited highly sensitive
      reduction-responsiveness, fast internalization, and efficient anticancer therapy.
      This approach displays a new potential of tellurylsulfide bond-containing
      nanocarriers for drug delivery.

PMID- 29168851
TI  - Non-staining visualization of embryogenesis and energy metabolism in medaka fish
      eggs using near-infrared spectroscopy and imaging.
AB  - The energy metabolism and embryogenesis of fertilized Japanese medaka eggs were
      investigated in vivo at the molecular level using near-infrared (NIR)
      spectroscopy and imaging. Changes in chemical components, such as proteins and
      lipids, in yolk sphere and embryonic body were studied over the course of
      embryonic development. Metabolic changes that represent variations in the
      concentrations and molecular compositions of proteins and lipids in the yolk
      part, particularly on the 1st day after fertilization and the day just before
      hatching, were successfully identified in the 4900-4000 cm-1 wavenumber region.
      The yolk components were shown to have specific functions at the very early and
      final stages of the embryonic development. Proteins with alpha-helix- or beta
      sheet-rich structures clearly showed the different variation patterns within the
      developing egg. Furthermore, the distribution of lipids could be selectively
      visualized using data from the higher wavenumber region. Detailed embryonic
      structures were clearly depicted in the NIR images using the data from the 6400
      5500 cm-1 region in which the embryo parts had some characteristic peaks due to
      unsaturated fatty acids. It was made clear that yolk and embryo parts had
      different components especially lipid components. The present study provides new
      insights into material variations in the fertilized egg during its growth. NIR
      imaging proved to be valuable in investigating the embryogenesis in vivo at the
      molecular level in terms of changes in biomolecular concentrations and
      compositions, metabolic differentiation, and detailed information about embryonic
      structures without the need for staining.

PMID- 29168852
TI  - Imidazole synthesis by transition metal free, base-mediated deaminative coupling
      of benzylamines and nitriles.
AB  - A transition metal free, straightforward synthetic method for the preparation of
      substituted imidazoles is reported herein. Base promoted, deaminative coupling of
      benzylamines with nitriles results in the one-step synthesis of 2,4,5
      trisubstituted imidazoles with liberation of ammonia. This protocol provides a
      practical strategy for the synthesis of valuable imidazole derivatives from
      readily available starting materials.

PMID- 29168853
TI  - Electrospun flexible poly(bisphenol A carbonate) nanofibers decorated with Ag
      nanoparticles as effective 3D SERS substrates for trace TNT detection.
AB  - A flexible 3D hybrid PC/Ag surface-enhanced Raman scattering (SERS) substrate was
      fabricated through the combination of electrospinning and in situ chemical
      reduction. Due to the rough surface morphology and the intricate 3D structure, a
      high density of Raman "hotspots" was formed at the junctions of cross-linked
      nanofibers, resulting in excellent sensitivity to a probe molecule (4
      aminothiophenol). The nanofibers were modified with l-cysteine to capture TNT
      molecules by the formation of a Meisenheimer complex, after which positively
      charged 4-ATP-labelled AgNPs were introduced to the system, which both generated
      more hotspots and led to a linear relationship between the TNT concentration and
      the SERS intensity of the labelled molecules. As a result, a good linear response
      ranging from 10-8 to 10-12 M was achieved, and the detection limit for TNT was as
      low as 2.05 * 10-13 M. This strategy demonstrates an ultra-sensitive approach for
      the detection of trace amounts of TNT, and a promising method for the detection
      of many other analogous explosives.

PMID- 29168854
TI  - Folded short azapeptide for conformation switching-based fluorescence sensing.
AB  - Herein, we report a conformation switching-based fluorescence sensing scheme
      using dipeptide-based amidothioureas (azapeptides) that contain a folded beta
      turn structure. Amidothiourea is equipped at its two termini with an electron
      acceptor and an electron donor or two fluorophores, such that it exhibits
      enhanced exciplex or excimer emission because of the turn structure in which the
      two termini are brought into close proximity; on the other hand, it exhibits a
      dramatic ratiometric fluorescence response upon anion binding to the thiourea
      moiety because of the resultant extended conformation of the anion binding
      complex.

PMID- 29168855
TI  - High adjuvant activity of layered double hydroxide nanoparticles and nanosheets
      in anti-tumour vaccine formulations.
AB  - Effective adjuvants in anti-tumour vaccine formulations are very important in the
      development of new-generation vaccines. In this study, two layered double
      hydroxide (LDH) nanomaterial forms, i.e. nanoparticles (NPs) and nanosheets
      (NSs), were synthesised and examined as adjuvants to provoke the immune responses
      for anti-tumour purpose. Immunogen ovalbumin (OVA) delivered by both
      nanomaterials induced much stronger humoral and cell-medicated immune responses,
      together with an immune stimulant (TLR9 ligand CpG), as evidenced by higher
      levels of IgG1, IgG2a and interferon-gamma. By comparison, LDH NSs showed higher
      activity to promote specific antibody responses than LDH NPs but with a similar
      cell-mediated immune response. The mice immunised with OVA-CpG vaccines
      formulated with both nanomaterials showed stronger inhibition of the inoculated
      tumour growth and had a longer survival. Altogether, these data indicate that LDH
      NPs and NSs can be used as potential nanoadjuvants for efficient protein-based
      anti-tumour vaccines.

PMID- 29168856
TI  - Temperature dependence of photoluminescence and hydrogen bonding revealed for the
      first time in a templated borate family: synthesis, structure and properties of a
      pentaborate [Emmim][B5O6(OH)4].
AB  - Herein, a templated borate, [Emmim][B5O6(OH)4] (denoted 1, Emmim = 1-ethyl-2,3
      dimethylimidazolium), has been synthesized. It is unexpectedly observed that 1
      exhibits a series of broadened luminescence curves from -183 to 75  degrees C,
      the emission intensities are measured as a decreasing function of temperature,
      and the line width of the PL emission is strongly enhanced when temperatures
      decrease below -100  degrees C. In addition to this, hydrogen bonding (H-B) in 1
      with distinctly enlarging trends was observed as the temperature increased. The
      influence of temperature on H-Bs and physical properties was explored through
      single crystal X-ray diffraction analysis, theoretical calculations, PL, and
      dielectric constant test. The results indicate that the temperature can impact
      weak H-Bs interactions and the PL can be seen as a prober to the varying of
      structure such as H-Bs in borate crystal.

PMID- 29168857
TI  - Ultrasensitive and towards single molecule SERS: general discussion.

PMID- 29168858
TI  - Ferromagnetic coupling in copper benzimidazole chloride: structural, mass
      spectrometry, magnetism, and DFT studies.
AB  - Herein, quasi-square planar CuII(Hmbm)Cl2 (CBC, Hmbm = (1-methyl-1H
      benzo[d]imidazol-2-yl)methanol) was arranged in a pseudo orthogonal way to form
      Cl-bridged chains, and further pipi interactions resulted in distorted hexagonal
      layers. DFT calculations reveal a bond strength order of Cu-Cl > Cu-O/N ? CuCl.
      ESI-MS data reveal several small fragments from CBC, but oligomeric [Cu], [Cu],
      and [Cu] for non-zero in-source energies; MS data indicates the occurrence of
      several chemical processes, viz. splitting of the ligand, oligomerization, and
      redox reaction of alcohol to aldehyde and CuII to CuI. Gibbs free energies for
      the fragments were estimated using DFT. The magnetic susceptibility was modeled
      with the ferromagnetic coupling J(Cu-Cl2aCu) = +0.99(30) cm-1 and J'(pipi) =
      +0.35(16) cm-1 and g = 2.38(2). HF-EPR determined the anisotropic g-values, gx =
      2.24, gy = 2.16, and gz = 2.09, and a hyperfine constant of Az = 450 G. DFT
      calculations from crystal structure data reveal a J(Cu-Cl2aCu) of +3.6 at 296 K
      and +4.1 cm-1 at 90 K that dominates the magnetic properties, whereas J'(pipi) =
      0.04 cm-1 is negligibly small.

PMID- 29168859
TI  - Correction: Composition-dependent charge transfer and phase separation in the V1
      xRexO2 solid solution.
AB  - Correction for 'Composition-dependent charge transfer and phase separation in the
      V1-xRexO2 solid solution' by D. Mikhailova, et al., Dalton Trans., 2017, 46, 1606
      1617.

PMID- 29168860
TI  - Raspberry differentially improves age-related declines in psychomotor function
      dependent on baseline motor ability.
AB  - Among older adults, falls are a leading cause of distress, pain, injury, loss of
      confidence, and ultimately, loss of independence and death. Previous studies in
      our laboratory have demonstrated that berry supplementation improves the age
      related declines in balance, muscle strength, and coordination that often lead to
      falls, even when initiated later in life. The purpose of this study was to
      explore the interaction between baseline motor performance and the daily intake
      of raspberry required to improve/preserve motor function. Aged male F344 (17 mo)
      rats were tested for baseline (pre-test) balance, muscle strength, and
      coordination, and divided into good, average, and poor performers based on their
      motor composite score. Rats in each category were fed with either a control, 1%,
      or 2% raspberry-supplemented diet for 8 weeks and then retested (post-test). Poor
      performers fed with 1% or 2% raspberry had higher post-test composite scores (p <
      0.05), while 2% raspberry lowered post-test composite scores in the good
      performers (p < 0.05), compared to control-fed rats. 1% and 2% raspberry appeared
      to preserve the performance of good performers and improve the performance of
      poor performers on plank walking (p < 0.05), while 2% raspberry improved post
      test grip strength of the poor performers (p < 0.05). Additionally, rats with
      lower post-diet composite scores had higher levels of serum IL-1beta levels (r = 
      0.347, p < 0.05). These findings identified poor performers as being the most
      likely to benefit from daily consumption of 1/2-2 cups of raspberry to
      improve/preserve motor function. Therefore, increased raspberry consumption may
      reduce fall risk, extend independence, and improve quality of life in the aging
      population.

PMID- 29168861
TI  - Binding of Al(iii) to synthetic RNA and metal-mediated strand aggregation.
AB  - Over the last few years, focused interest in aluminum has been heightened by
      recent studies regarding its health effects. Its possible relation with chronic
      diseases makes it convenient to address more in depth the reactivity of aluminum
      with biologically relevant molecules. The present work investigates the
      interaction of the aluminum ion with two synthetic RNAs, poly(rA) and poly(rU),
      through a detailed thermodynamic and kinetic study. The trivalent aluminum ion
      was kept in solution by complexation with the cacodylate anion, even at neutral
      pH, thus making the study with biological molecules feasible. The results
      obtained by spectrophotometry, circular dichroism, viscometry and thermal
      stability measurements indicate that aluminium strongly interacts with single and
      duplex RNA structures. The kinetic experiments point out that, even though
      cacodylate is required to keep the metal in solution, it actually inhibits the
      reaction of aluminum with RNA as it converts the metal into an unreactive dimer
      species. Notably, further interaction occurred in an excess of the
      aluminum/cacodylate complex, inducing aggregation of single-stranded RNAs. An
      analysis of the kinetic data has shown that the modes of aggregation of the two
      RNAs differ and such a difference can be ascribed to the diverse polynucleotide
      secondary structures. The observed stabilization of multiple-stranded systems by
      aluminum can serve as a model for future studies due to the interest aroused by
      this metal in the study of non-canonical nucleic acid structures.

PMID- 29168862
TI  - Inhibition of advanced glycation endproducts during fish sausage preparation by
      transglutaminase and chitosan oligosaccharides induced enzymatic glycosylation.
AB  - Advanced glycation endproducts (AGEs) are the harmful products of non-enzymatic
      reactions in foods formed during the heating process. In order to reduce the
      content of AGEs in foods, the inhibitory effect of different proportions of
      transglutaminase (TGase) and chitosan oligosaccharides (COS) on the AGEs of
      seabream fish meat sausage was studied. The results indicated that the TGase/COS
      ratio of 1 : 1 could inhibit the formation of AGEs, showing especially a
      decreased Nepsilon-carboxymethyl-lysine (CML) content and a twice higher
      inhibition rate (36.4%) than that by aminoguanidine (17.4%), a commonly effective
      positive inhibitor of AGEs. The data of lysine, fructosamine, and glucosamine
      contents, combined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      analyses, demonstrated that cross-linking of proteins and glycosylation of
      glutamine induced by TGase and COS resulted in steric hindrance that inhibited
      glycation. These findings revealed that TGase catalyzed glycosylation with COS
      differently from general antioxidants had potential as an effective treatment to
      inhibit the formation of AGEs in fishery products.

PMID- 29168863
TI  - Structure characterization of a novel polysaccharide from Hericium erinaceus
      fruiting bodies and its immunomodulatory activities.
AB  - A novel polysaccharide fraction (HEP-S) was extracted and isolated from the
      fruiting bodies of Hericium erinaceus. Structural characterization revealed that
      HEP-S had an average molecular weight of 1.83 * 104 Da and consisted of rhamnose,
      fucose, mannose, glucose and galactose at a molar ratio of 1.47 : 0.93 : 1.36 :
      8.68 : 4.08. Periodate oxidation-Smith degradation and NMR analysis showed that
      the main linkage types of HEP-S were composed of (1->)-alpha-d-Glc, (1->3,4)
      alpha-d-Glc, (1->6)-alpha-d-Gal, (1->3,4)-beta-d-Man, (1->3,6)-alpha-Rha and (1
      >2)-beta-l-Fuc. The immunomodulatory assay indicated that HEP-S could
      significantly enhance the pinocytic and phagocytic capacity and promote the
      secretion of nitric oxide and pro-inflammatory cytokines by activating the
      corresponding mRNA and protein expression in RAW 264.7 cells involving a toll
      like receptor 2 membrane receptor. Besides, HEP-S was also found to improve the
      adaptive immune function by enhancing T and B lymphocyte proliferation and
      increasing the interleukin-2, interleukin-4 and interferon-gamma secretion in
      spleen lymphocytes. These results suggested that HEP-S could be used as a
      potential immunoregulatory agent in functional foods.

PMID- 29168864
TI  - Using time-resolved photoelectron spectroscopy to unravel the electronic
      relaxation dynamics of photoexcited molecules.
AB  - Time-resolved photoelectron spectroscopy measurements combined with quantum
      chemistry and dynamics calculations allow unprecedented insight into the
      electronic relaxation mechanisms of photoexcited molecules in the gas-phase. In
      this Tutorial Review, we explain the essential concepts linking photoelectron
      spectroscopy measurements with electronic structure and how key features on the
      potential energy landscape are identified using quantum chemistry and quantum
      dynamics calculations. We illustrate how time-resolved photoelectron spectroscopy
      and theory work together using examples ranging in complexity from the
      prototypical organic molecule benzene to a pyrrole dimer bound by a weak N-Hpi
      interaction and the green fluorescent protein chromophore.

PMID- 29168865
TI  - Syntheses, crystal structures, DFT calculations, protein interaction and
      anticancer activities of water soluble dipicolinic acid-imidazole based
      oxidovanadium(iv) complexes.
AB  - Three novel water soluble neutral mononuclear oxidovanadium(iv) complexes 1-3,
      [VOLB2] (where H2L = dipicolinic acid (DPA) and B = imidazole (1)/1
      methylimidazole (2)/1-allylimidazole (3)), were synthesized by the reaction of
      [VOL(H2O)2] with imidazole/1-methylimidazole/1-allylimidazole in ethanol. The
      complexes were thoroughly characterized by elemental analysis, IR, UV-Vis and EPR
      spectroscopy, magnetic susceptibility, cyclic voltammetry and single crystal X
      ray diffraction techniques. In all the complexes the vanadium(iv) centre assumes
      a distorted octahedral environment. All the three complexes have similar
      structures and contain a range of intramolecular interactions such as hydrogen
      bonding, C-Hpi, and pipi stacking dominating their supramolecular architectures.
      A thermal study of the complexes was carried out to analyze their stability. The
      energy of non-covalent interactions and frontier orbitals for the complexes were
      also calculated by DFT. In order to investigate the binding interactions and
      conformational changes of the secondary structure of bovine serum albumin (BSA)
      with the complexes, absorption, fluorimetric titration and circular dichroism
      measurements in aqueous medium were carried out. Molecular docking studies have
      also been carried out to understand the binding modes and interaction patterns of
      the oxidovanadium(iv) complexes with BSA. The anticancer activities of the ligand
      and complexes 1-3 were tested against the human hepatic carcinoma cell line
      Hep3B. The complexes showed prominent cytotoxicity towards cancer cells.

PMID- 29168866
TI  - Chemical composition and bioactive properties of the wild mushroom Polyporus
      squamosus (Huds.) Fr: a study with samples from Romania.
AB  - In Eastern Europe, wild mushrooms are widely collected in mountain areas and used
      for their medicinal properties or as healthy foods. This study aimed at
      determining the chemical composition (nutritional value, free sugars, organic
      acids, phenolic compounds, fatty acids and tocopherols) and bioactive properties
      (antioxidant, antimicrobial and antiquorum sensing) of wild Polyporus squamosus
      (Huds.) Fr from Romania. The results indicate that the fruiting bodies of P.
      squamosus are rich in carbohydrates (74.22 g per 100 g dw) and proteins (18.7 g
      per 100 g dw). Trehalose was the main free sugar, while malic acid was the
      organic acid detected in the highest amount (2.21 g per 100 g dw), and p
      hydroxybenzoic acid was the main phenolic compound. Among tocopherols, beta
      tocopherol was the most abundant form (114.7 MUg per 100 g dw). Additionally,
      regarding the fatty acids' pattern, polyunsaturated acids represent more than 57%
      of all fatty acids, followed by monounsaturated fatty acids (24.96%). The highest
      measured antioxidant effect of P. squamosus extract was found using the TBARS
      inhibition assay (EC50 = 0.22 mg mL-1), followed by the beta-carotene/linoleate
      assay (EC50 = 1.41 mg mL-1). A minimal inhibitory concentration of the tested
      extracts was obtained between 0.61-20.4 mg mL-1, while the bactericidal effect
      was achieved between 1.2-40.8 mg mL-1. Antibiofilm potential was obtained at all
      tested concentrations, and subinhibitory concentrations of the extract exhibited
      an antiquorum effect and reduced the formation of P. aeruginosa pili, which all
      together influenced the virulence of this bacterium. Due to the investigated
      bioactivities and compounds of P. squamosus and its well-balanced nutritional
      profile, this mushroom can be further used as a medicinal ingredient based on its
      antioxidative and antimicrobial potential.

PMID- 29168867
TI  - The protective effect of phloretin in osteoarthritis: an in vitro and in vivo
      study.
AB  - Osteoarthritis (OA) is a degenerative joint disease characterized by the
      degradation and inflammation of cartilage. Phloretin, a type of dihydrochalcone
      mainly found in apples and apple-derived products, has been reported to possess
      various potent biological effects such as antioxidant, anticancer, anti
      inflammatory, and immunomodulatory. However, the anti-inflammatory effects of
      phloretin on OA have not been reported. This study was aimed at assessing the
      effects of phloretin on human OA chondrocytes. Human OA chondrocytes were
      pretreated with phloretin (10, 30, and 100 MUM) for 2 h and subsequently
      stimulated with IL-1beta for 24 h. The production of NO, PGE2, TNF-alpha, and IL
      6 was determined using the Griess reagent and ELISAs. The mRNA expression of COX
      2, iNOS, MMP-3, MMP-13, and ADAMTS-5 was measured by real-time PCR. Changes in
      the protein expression of COX-2, iNOS, MMPs, ADAMTS, aggrecan, collagen-II, NF
      kappaB, and the PI3K/Akt signaling pathway were detected by western blotting. In
      this study, we found that phloretin significantly inhibited the IL-1beta-induced
      production of NO, PGE2, TNF-alpha, and IL-6, the expression of COX-2, iNOS, MMP
      3, MMP-13, and ADAMTS-5, and the degradation of aggrecan and collagen-II in human
      OA chondrocytes. Furthermore, phloretin dramatically suppressed the IL-1beta
      stimulated phosphorylation of PI3K/Akt and activation of NF-kappaB in human OA
      chondrocytes. In addition, treatment with phloretin not only prevented the
      destruction of cartilage and the thickening of subchondral bone but also relieved
      synovitis in a mouse model of OA. Moreover, immunohistochemical results showed
      that phloretin significantly decreased the expression of MMP-13 and increased the
      expression of collagen-II in OA in mice. In conclusion, these results suggest
      that phloretin may be a potential agent for the treatment of OA.

PMID- 29168868
TI  - Structural elucidation and immunostimulatory activity of a new polysaccharide
      from Cordyceps militaris.
AB  - A new polysaccharide (CMPB90-1) was isolated from cultured Cordyceps militaris by
      alkaline extraction. The chemical structure of CMPB90-1 was determined by
      analysis of physicochemical and spectral data. The backbone of CMPB90-1 is
      composed of (1->6)-linked alpha-d-glucopyranosyl and (1->3)-linked alpha-d
      glucopyranosyl residues, with branching at O-6, which consists of (1->4)-linked
      beta-d-mannopyranosyl and (1->6)-linked alpha-d-glucopyranosyl residues,
      respectively. beta-d-Galactopyranosyl residues is the terminal unit. In vitro
      immunomodulatory assay revealed that CMPB90-1 promoted proliferation of splenic
      lymphocytes, enhanced cytotoxicity of NK cells and promoted lymphocyte secretion
      of the cytokine interleukin-2. Besides, CMPB90-1 upregulated T-cell
      subpopulation, strengthened phagocytosis function of macrophages and induced
      their M1 polarization. The mechanism of the effects might be due to the
      activation of TLR2, MAPK and NF-kappaB pathways. The results proposed that CMPB90
      1 can be researched and developed as a new functional food.

PMID- 29168869
TI  - Amentoflavone improves cardiovascular dysfunction and metabolic abnormalities in
      high fructose and fat diet-fed rats.
AB  - Metabolic syndrome (MS) is a leading cause of mortality and morbidity in Western
      countries. Amentoflavone (AMF) is a polyphenolic compound which has been found to
      exhibit various biological activities. In this study, we investigated the
      protective effects of AMF against cardiovascular and liver dysfunction in high
      fructose and fat diet (HFFD)-induced MS rats. AMF could evidently inhibit the
      changes of general metabolic parameters, including body weight, fat mass, insulin
      level, and glucose tolerance activity. AMF markedly protected against
      cardiovascular dysfunction, as evidenced by a decrease of systolic blood
      pressure, left ventricular internal diameter in diastole (LVIDd) and left
      ventricular posterior wall thickness in diastole (LVPWd); increase of fractional
      shortening; and decrease of ejection fraction, relative wall thickness, estimated
      LV mass, cardiac stiffness and LV wet weight in HFFD-fed rats. AMF also inhibited
      the increase of aortic vasoconstriction in response to phenylephrine and
      increased relaxation in response to acetylcholine in HFFD-fed rats. AMF reversed
      the HFFD-induced decrease of nitrogen oxide level, increase of type 1 Ang II
      receptor (AT-1A) expression and decrease of AT-2A expression. AMF reduced
      histological and functional injury and lipid accumulation in livers in MS rats.
      AMF also inhibited HFFD-induced oxidative stress, as reflected by the decrease of
      thiobarbituric acid reactive substance content, increase of GSH level, increase
      of superoxide dismutase and catalase activities, and decrease of NADPH oxidase
      activities. In summary, we showed that AMF exhibited protective effects against
      cardiovascular dysfunction and liver injury in MS rats. Inhibition of the renin
      angiotensin system and oxidative stress contributes to cardiovascular and liver
      protective activities. Our data provide novel insights into the beneficial
      effects of AMF against MS.

PMID- 29168870
TI  - Hybrid compounds assembled from copper-triazole complexes and phosphomolybdic
      acid as advanced catalysts for the oxidation of olefins with oxygen.
AB  - Two hybrid compounds, namely [Cu(3atrz)4][PMoMoVO40] (1) and
      [Cu(3atrz)6][PMo12O40]2 (2), were synthesized through hydrothermal reactions of 3
      amino-1,2,4-triazole (3atrz), phosphomolybdic acid (PMA) and appropriate copper
      salts. Crystal structure analysis reveals that compound 1 contains one
      dimensional Cu-3atrz chains. The unit of compound 2 contains a double
      calyx[3]arene-shaped hexamer, which is composed of six two-coordinated CuI atoms
      and six 3atrz ligands. Both compounds 1 and 2 present a three-dimensional hybrid
      structure, which is built by the self-assembly of Cu-3atrz clusters and Keggin
      type PMA units. The resulting hybrid compounds can act as highly efficient
      heterogeneous catalysts for the selective oxidation of olefins with molecular
      oxygen as the oxidant in the presence of a trace amount of tert-butyl
      hydroperoxide (t-BuOOH). Their excellent catalytic properties can be mainly
      attributed to the existence of stabilized CuI complexes with an appropriate
      chemical environment and a spacious structure, which can interact with t-BuOOH to
      form catalytic sites for the direct activation of O2. This work demonstrates that
      the hybrid compounds assembled from copper-3atrz complexes and phosphomolybdic
      acid may have great potential in molecular O2-mediated catalytic oxidation
      reactions, which can certainly build a platform for deep insight into the
      biologically relevant catalytic oxidation processes.

PMID- 29168871
TI  - Probing impaired neurogenesis in human brain organoids exposed to alcohol.
AB  - The fetal brain is highly vulnerable to ethanol exposure, which can trigger
      various long-term neuronal disabilities and cognitive dysfunctions. However, a
      comprehensive understanding of fetal brain development under ethanol exposure is
      challenging due to the limitations of animal models. Here, we propose a human
      induced pluripotent stem cell (hiPSC)-based 3D brain organoid model, and explore
      the mechanisms underlying neural dysfunctions in prenatal alcohol exposure (PAE)
      in vitro. Brain organoids were examined to resemble brain organogenesis in vivo
      at early stages during gestation, with specific features of neuronal
      differentiation, brain regionalization, and cortical organization. With ethanol
      exposure, the brain organoids displayed attenuated neurite outgrowth and skewed
      neural maturation. Transcriptome analysis identified a series of new markedly
      altered genes and enriched pathways, such as GSX2, RSPO2, and the Hippo signaling
      pathway. These genes or pathways, to our knowledge, were reported to be involved
      in ethanol-induced impaired neurogenesis for the first time. Our new findings
      might facilitate better understanding of the various postnatal neural disorders
      observed in individuals with PAE.

PMID- 29168872
TI  - Organoselenium compounds as mimics of selenoproteins and thiol modifier agents.
AB  - Selenium is an essential trace element for animals and its role in the chemistry
      of life relies on a unique functional group: the selenol (-SeH) group. The
      selenol group participates in critical redox reactions. The antioxidant enzymes
      glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) exemplify important
      selenoproteins. The selenol group shares several chemical properties with the
      thiol group (-SH), but it is much more reactive than the sulfur analogue. The
      substitution of S by Se has been exploited in organic synthesis for a long time,
      but in the last 4 decades the re-discovery of ebselen (2-phenyl-1,2
      benzisoselenazol-3(2H)-one) and the demonstration that it has antioxidant and
      therapeutic properties has renovated interest in the field. The ability of
      ebselen to mimic the reaction catalyzed by GPx has been viewed as the most
      important molecular mechanism of action of this class of compound. The term GPx
      like or thiol peroxidase-like reaction was previously coined in the field and it
      is now accepted as the most important chemical attribute of organoselenium
      compounds. Here, we will critically review the literature on the capacity of
      organoselenium compounds to mimic selenoproteins (particularly GPx) and discuss
      some of the bottlenecks in the field. Although the GPx-like activity of
      organoselenium compounds contributes to their pharmacological effects, the
      superestimation of the GPx-like activity has to be questioned. The ability of
      these compounds to oxidize the thiol groups of proteins (the thiol modifier
      effects of organoselenium compounds) and to spare selenoproteins from
      inactivation by soft-electrophiles (MeHg+, Hg2+, Cd2+, etc.) might be more
      relevant for the explanation of their pharmacological effects than their GPx-like
      activity. In our view, the exploitation of the thiol modifier properties of
      organoselenium compounds can be harnessed more rationally than the use of low
      mass molecular structures to mimic the activity of high mass macromolecules that
      have been shaped by millions to billions of years of evolution.

PMID- 29168873
TI  - Throughput enhancement of parallel step emulsifier devices by shear-free and
      efficient nozzle clearance.
AB  - Step emulsification is an attractive method for production of monodisperse drops.
      Its main advantage is the ability to parallelize many step emulsifier nozzles to
      achieve high production rates. However, step emulsification is sensitive to any
      obstructions at the nozzle exit. At high production rates, drops can accumulate
      at nozzle exits, disturb the formation of subsequent drops and impair
      monodispersity. As a result, parallelized step emulsifier devices typically do
      not work at maximum productivity. Here a design is introduced that parallelizes
      hundreds of step emulsifier nozzles, and effectively removes drops from the
      nozzle exits. The drop clearance is achieved by an open collecting channel, and
      is aided by buoyancy. Importantly, this clearance method avoids the use of a
      continuous phase flow for drop clearance and hence no shear is applied on the
      forming drops. The method works well for a wide range of drops, sizing from 30 to
      1000 MUm at production rates of 0.03 and 10 L per hour and achieved by 400 and
      120 parallelized nozzles respectively.

PMID- 29168874
TI  - Bioreactor model of neuromuscular junction with electrical stimulation for
      pharmacological potency testing.
AB  - In vitro models of the neuromuscular junction (NMJ) are emerging as a valuable
      tool to study synaptogenesis, synaptic maintenance, and pathogenesis of
      neurodegenerative diseases. Many models have previously been developed using a
      variety of cell sources for skeletal muscle and motoneurons. These models can
      advanced by integrating beneficial features of the native developmental milieu of
      the NMJ. We created a functional in vitro model of NMJ by bioreactor cultivation
      of transdifferentiated myocytes and stem cell-derived motoneurons, in the
      presence of electrical stimulation. In conjunction with a coculture medium,
      electrical stimulation resulted in improved maturation and function of
      motoneurons and myocytes, as evidenced by mature cellular structures, increased
      expression of neuronal and muscular genes, clusterization of acetylcholine
      receptors (AChRs) in the vicinity of motoneurons, and the response to glutamate
      stimulation. To validate the model and demonstrate its utility for
      pharmacological testing, we documented the potency of drugs that affect key
      pathways during NMJ signal transduction: (i) acetylcholine (ACh) synthesis, (ii)
      ACh vesicular storage, (iii) ACh synaptic release, (iv) AChR activation, and (v)
      ACh inactivation in the synaptic cleft. The model properly responded to the drugs
      in a concentration-dependent manner. We thus propose that this in vitro model of
      NMJ could be used as a platform in pharmacological screening and controlled
      studies of neuromuscular diseases.

PMID- 29168875
TI  - Appreciation of symmetry in natural product synthesis.
AB  - Covering: 2012 to June 2017This review aims to show that complex natural product
      synthesis can be streamlined by taking advantage of molecular symmetry. Various
      strategies to construct molecules with either evident or hidden symmetry are
      illustrated. Insights regarding the origins and adjustments of these strategies
      as well as inspiring new methodological developments are deliberated. When a
      symmetric strategy fails, the corresponding reason is analysed and an alternative
      approach is briefly provided. Finally, the importance of exploiting molecular
      symmetry and future research directions are discussed.

PMID- 29168876
TI  - A compartmentalized microfluidic chip with crisscross microgrooves and
      electrophysiological electrodes for modeling the blood-retinal barrier.
AB  - The interconnection of different tissue-tissue interfaces may extend organ-on
      chips to a new generation of sophisticated models capable of recapitulating more
      complex organ-level functions. Single interfaces are largely recreated in organ
      on-chips by culturing the cells on opposite sides of a porous membrane that
      splits a chamber in two or by connecting the cells of two adjacent compartments
      through microchannels. However, it is difficult to interconnect more than one
      interface using these approaches. To address this challenge, we present a novel
      microfluidic device where cells are arranged in parallel compartments and are
      highly interconnected through a grid of microgrooves, which facilitates paracrine
      signaling and heterotypic cell-cell contact between multiple tissues. In
      addition, the device includes electrodes on the substrate for the measurement of
      transepithelial electrical resistance (TEER). Unlike conventional methods for
      measuring the TEER where electrodes are on each side of the cell barrier, a
      method with only electrodes on the substrate has been validated. As a proof-of
      concept, we have used the device to mimic the structure of the blood-retinal
      barrier by co-culturing primary human retinal endothelial cells (HREC), a human
      neuroblastoma cell line (SH-SY5Y), and a human retinal pigment epithelial cell
      line (ARPE-19). Cell barrier formations were assessed by a permeability assay,
      TEER measurements, and ZO-1 expression. These results validate the proposed
      microfluidic device with microgrooves as a promising in vitro tool for the
      compartmentalization and monitoring of barrier tissues.

PMID- 29168877
TI  - Full-angle tomographic phase microscopy of flowing quasi-spherical cells.
AB  - We report a reliable full-angle tomographic phase microscopy (FA-TPM) method for
      flowing quasi-spherical cells along microfluidic channels. This method lies in a
      completely passive optical system, i.e. mechanical scanning or multi-direction
      probing of the sample is avoided. It exploits the engineered rolling of cells
      while they are flowing along a microfluidic channel. Here we demonstrate
      significant progress with respect to the state of the art of in-flow TPM by
      showing a general extension to cells having almost spherical shapes while they
      are flowing in suspension. In fact, the adopted strategy allows the accurate
      retrieval of rotation angles through a theoretical model of the cells' rotation
      in a dynamic microfluidic flow by matching it with phase-contrast images
      resulting from holographic reconstructions. So far, the proposed method is the
      first and the only one that permits to get in-flow TPM by probing the cells with
      full-angle, achieving accurate 3D refractive index mapping and the simplest
      optical setup, simultaneously. Proof of concept experiments were performed
      successfully on human breast adenocarcinoma MCF-7 cells, opening the way for the
      full characterization of circulating tumor cells (CTCs) in the new paradigm of
      liquid biopsy.

PMID- 29168878
TI  - Quercetin and fisetin enhanced the small intestine cellular uptake and plasma
      levels of epi-catechins in in vitro and in vivo models.
AB  - Quercetin and fisetin, known as catechol-containing flavonoids, could positively
      affect the absorption of catechins due to their strong affinity for catechol-O
      methyl transferase (COMT), which can methylate and cause the excretion of
      catechins. The current study examined the effect of quercetin and fisetin on the
      absorption of epi-catechins (ECs) by using a Caco-2 cell line and an in vivo
      model. The intestinal transport of total catechins by Caco-2 cells was enhanced
      from 1.3- to 1.6-fold and 1.4- to 1.7-fold by adding quercetin and fisetin,
      respectively, compared to the control. It was even higher in the treatment with a
      mixture of quercetin and fisetin. While EC had the highest value of intestinal
      transport (169% of the control) in 10% quercetin treatment, EGC (235%), EGCG
      (244%), and ECG (242%) were significantly transported in the treatment with a 5%
      mixture of quercetin and fisetin (p < 0.05). In an in vivo pharmacokinetic study,
      the values of the area under the plasma concentration-time curve (AUC, ng h mL-1)
      were also higher in rats orally administered EGCG with 10% quercetin (365.5 +/-
      25.5) or 10% fisetin (825.3 +/- 46.7) than in those administered EGCG only (111.3
      +/- 13.1). Methylated quercetin and methylated fisetin were determined to be m/z
      317.24 and m/z 301.25 [M + H]+ with their own product ions, respectively. The
      results indicate that quercetin or fisetin is superior to ECs for methylation by
      COMT.

PMID- 29168879
TI  - 1p36 deletion results in a decrease in glycosaminoglycans which is associated
      with aggressiveness in neuroblastic tumors.
AB  - Despite our deep understanding of neuroblastic tumors, some patients still suffer
      treatment failure, so pre-treatment risk stratification still requires
      improvement and the search for new therapeutic targets must continue. Here we
      correlated prognostic clinical and biological features of neuroblastic tumors
      with the density of extracellular matrix glycosaminoglycans (the main components
      of the extracellular matrix 'ground substance'), in nearly 400 primary samples.
      We also studied the relationship between the density of extracellular matrix
      glycosaminoglycans and the expression of B3GALT6, an enzyme required for their
      synthesis. We associated a decrease in glycosaminoglycans with neuroblastomas
      that were histopathologically poorly-differentiated or undifferentiated, as well
      as with metastatic disease, and 1p36 deleted tumors. This decrease in
      glycosaminoglycans was also related to abnormal nuclear B3GALT6 expression in
      neuroblastic cells. These findings point towards the importance of the ground
      substance in the aggressiveness of neuroblastic tumors, which should therefore be
      considered when developing novel therapies for treating neuroblastomas.

PMID- 29168880
TI  - Cost-Effectiveness of a Care Transitions Program in a Multimorbid Older Adult
      Cohort.
AB  - BACKGROUND/OBJECTIVES: Facing penalties for preventable 30-day hospital
      readmissions, many provider groups have implemented programs to remedy this
      problem, but the cost efficacy and value of such programs are not well
      delineated. The objective was to compare total cost of care over 30 days of
      individuals enrolled in the Mayo Clinic Care Transitions (MCCT) program and
      individuals not enrolled. DESIGN: Retrospective cohort study using secondary data
      analysis of a previously published cohort study. SETTING: Mayo Clinic, Rochester,
      Minnesota. PARTICIPANTS: MCCT participants (n = 363) and individuals in a
      propensity-matched referent cohort (n = 365). INTERVENTION: MCCT program
      enrollment. MEASUREMENTS: The primary outcome was total cost of care over 30 days
      after hospital discharge. A 2-part modeling strategy was used to analyze 30-day
      costs: whether individuals had non-zero costs during the 30 days after discharge
      and a generalized linear model for individuals who incurred costs. Potential
      heterogeneous effects of the MCCT program were examined according to decile of 30
      day costs using quantile regression. RESULTS: Mean age was 83 in both groups.
      Adjusted mean 30-day cost after hospitalization was $3,363 (95% confidence
      interval (CI) = $2,512-4,213) in the MCCT group and $4,161 (95% CI = $3,096
      5,226) in the control group (P = .25). Cost savings of $2,744 (P = .008) at the
      eighth decile and $3,388 (P = .20) at the ninth decile were demonstrated. Thus,
      the only statistically significant differences were in the post hoc subgroup
      analysis in the highest-cost subgroups. CONCLUSION: We did not find a difference
      in overall mean costs between the MCCT group and the control group, although
      intervention participants in the upper deciles of costs appeared to experience
      lower costs than controls. A larger study cohort might better determine the value
      of the intervention.

PMID- 29168881
TI  - Quality of life in a randomized trial of early closure of temporary ileostomy
      after rectal resection for cancer (EASY trial).
AB  - BACKGROUND: A temporary ileostomy may reduce symptoms from anastomotic leakage
      after rectal cancer resection. Earlier results of the EASY trial showed that
      early closure of the temporary ileostomy was associated with significantly fewer
      postoperative complications. The aim of the present study was to compare health
      related quality of life (HRQOL) following early versus late closure of a
      temporary ileostomy. METHODS: Early closure of a temporary ileostomy (at 8-13
      days) was compared with late closure (at more than 12 weeks) in a multicentre RCT
      (EASY) that included patients who underwent rectal resection for cancer.
      Inclusion of participants was made after index surgery. Exclusion criteria were
      signs of anastomotic leakage, diabetes mellitus, steroid treatment, and signs of
      postoperative complications at clinical evaluation 1-4 days after rectal
      resection. HRQOL was evaluated at 3, 6 and 12 months after resection using the
      European Organisation for Research and Treatment of Cancer (EORTC) questionnaires
      QLQ-C30 and QLQ-CR29 and Short Form 36 (SF-36(r)). RESULTS: There were 112
      patients available for analysis. Response rates of the questionnaires were 82-95
      per cent, except for EORTC QLQ-C30 at 12 months, to which only 54-55 per cent of
      the patients responded owing to an error in questionnaire distribution. There
      were no clinically significant differences in any questionnaire scores between
      the groups at 3, 6 or 12 months. CONCLUSION: Although the randomized study found
      that early closure of the temporary ileostomy was associated with significantly
      fewer complications, this clinical advantage had no effect on the patients'
      HRQOL. Registration number: NCT01287637 (https://www.clinicaltrials.gov).

PMID- 29168883
TI  - Prevalence of Frailty and Associated Factors in the Community-Dwelling Population
      of China.
AB  - BACKGROUND/OBJECTIVES: Frailty in older adults predicts dependence and mortality
      and is a major challenge for healthcare systems in countries with rapidly aging
      populations. Little is known about frailty in China. We investigated the
      prevalence and associated risk factors of frailty in older adults in China.
      DESIGN: Cross-sectional. SETTING: Data were obtained from the China Comprehensive
      Geriatric Assessment Study, conducted in 2011-12, which was the first uniform
      comprehensive assessment system adopted in China. PARTICIPANTS: Older adults from
      7 cities were selected based on well-established cluster, stratification, and
      random selection statistical sampling techniques (N = 5,844). MEASUREMENTS: The
      Comprehensive Geriatric Assessment-Frailty Index was measured based on
      demographic characteristics, physical health, physical function, living behavior
      and social function, mental health, and cognitive function. RESULTS: The overall
      weighted prevalence of frailty was 9.9%: 12.7% in southwestern China, 11.0% in
      northern China, 5.9% in northwestern China, 5.0% in south-central China, 2.5% in
      eastern China, and 2.3% in northeastern China. The prevalence of frailty
      increased with age and was significantly higher in women and those living in
      rural areas. After adjusting for sex, age, area, region, and education, activity
      of daily living impairment was the strongest risk factor for frailty. Chronic
      diseases, depression, poor lifestyle, and geriatric syndromes were also
      independent risk factors. CONCLUSION: Our study provides epidemiological
      characteristics and the risk factors of frailty in China; the findings indicate
      greater regional disparities. Efforts to promote physical, psychological, and
      social health in older adults are a core objective of health policy, especially
      in women and those living in rural areas.

PMID- 29168882
TI  - Fibroblast growth factor 2 regulates activity and gene expression of human post
      mitotic excitatory neurons.
AB  - Many neuropsychiatric disorders are thought to result from subtle changes in
      neural circuit formation. We used human embryonic stem cells and induced
      pluripotent stem cells (hiPSCs) to model mature, post-mitotic excitatory neurons
      and examine effects of fibroblast growth factor 2 (FGF2). FGF2 gene expression is
      known to be altered in brain regions of major depressive disorder (MDD) patients
      and FGF2 has anti-depressive effects in animal models of depression. We generated
      stable inducible neurons (siNeurons) conditionally expressing human neurogenin-2
      (NEUROG2) to generate a homogenous population of post-mitotic excitatory neurons
      and study the functional as well as the transcriptional effects of FGF2. Upon
      induction of NEUROG2 with doxycycline, the vast majority of cells are post
      mitotic, and the gene expression profile recapitulates that of excitatory neurons
      within 6 days. Using hES cell lines that inducibly express NEUROG2 as well as
      GCaMP6f, we were able to characterize spontaneous calcium activity in these
      neurons and show that calcium transients increase in the presence of FGF2. The
      FGF2-responsive genes were determined by RNA-Seq. FGF2-regulated genes previously
      identified in non-neuronal cell types were up-regulated (EGR1, ETV4, SPRY4, and
      DUSP6) as a result of chronic FGF2 treatment of siNeurons. Novel neuron-specific
      genes were also identified that may mediate FGF2-dependent increases in synaptic
      efficacy including NRXN3, SYT2, and GALR1. Since several of these genes have been
      implicated in MDD previously, these results will provide the basis for more
      mechanistic studies of the role of FGF2 in MDD.

PMID- 29168884
TI  - Transformation of a Geriatric Department in China.
AB  - China has the world's largest elderly population, and the oldest-old population,
      with a current disability rate greater than 50%, will triple in the next 35
      years. The field of geriatrics is young, because almost all geriatric departments
      were established after 2000, and so faces many challenges. Management of diseases
      and hospital care is the focus. Senior physicians were trained in other
      subspecialties, such as pulmonary or cardiology, and junior physicians entered
      geriatrics departments as masters or doctorate students after medical school. The
      inadequacy of post-acute and long-term care facilities has caused long hospital
      stays. There are no national systematic geriatric training programs, national
      board examinations, or qualifications in geriatrics. These challenges were used
      as a framework for guiding changes in the Department of Geriatrics at West China
      Hospital, Sichuan University. These changes have included international
      experiences and collaboration for physicians and nurses, revision of departmental
      conferences, and special training for a unique group of caregivers called hugong
      (untrained caregivers hired by families to be at the bedside of hospitalized
      individuals). The most significant yet challenging part of the transformation has
      been to develop and modify Western-based geriatric models of care (e.g., Acute
      Care of the Elderly unit, delirium prevention and management models, palliative
      care). Lastly, the department established Tianxia (in the sky) Doctors, an
      internet-based platform to connect the department's interdisciplinary team to
      other hospitals, nursing institutions, home-based care service stations,
      community health service centers, and pharmacies throughout the region.

PMID- 29168886
TI  - Phytochemical profiling of anti-inflammatory Lavandula extracts via RP-HPLC-DAD
      QTOF-MS and -MS/MS: Assessment of their qualitative and quantitative differences.
AB  - As for other aromatic plants, there are many analytical methods for the
      determination of volatile compounds in lavender essential oils. Alternatively, in
      this study RP-HPLC-DAD-QTOF-MS was used for the profiling of the phytochemical
      constituents of hydromethanolic extracts of L. stoechas and L. dentata, which
      were obtained by pressurized liquid extraction. The spectrometric data revealed
      complex profiles constituted of a wide range of polar and semi-polar
      phytochemicals, mainly, phenolic compounds (68). Most phenolic compounds (55)
      have not been previously reported in Lavandula; such is the case of caffeic acid
      based oligomers. Moreover, the analytical method was validated for the
      determination of phenolic compounds. Our findings showed both qualitative and
      quantitative differences between the extracts. In this sense, while
      hydroxycinnamic acids made up the largest class in both extracts, flavones were
      the most abundant class, accounting for 10.44 g (L. dentata) and 4.85 g (L.
      stoechas) per 100 g of dry extract. In conclusion, this analytical method
      provided essential information about the phytochemical composition of the studied
      medicinal plants, revealing novel constituents that were probably hidden for
      others. In addition, these results may help to understand the anti-inflammatory
      properties of these extracts.

PMID- 29168885
TI  - Distribution of peripheral dendritic cells in patients with HBV infection or
      spleen and kidney deficiency.
AB  - Spleen and kidney deficiency syndrome (SKD), a Traditional Chinese Medicine (TCM)
      syndrome, is the fundamental mechanisms of TCM. We aim to investigate the
      distribution of peripheral dendritic cells (DCs) in HBV patients with SKD or non
      SKD. Peripheral venous blood from patients with HBV infection and healthy
      volunteers was collected to extract PBMC, and flow cytometry assay was used to
      measure the distribution of DCs subsets, including myeloid dendritic cells (mDCs)
      and plasmacytoid dendritic cells (pDCs). For the number of pDCs, it was higher in
      control group and non-SKD group, compared with HBV infection group and SKD group,
      respectively. For the number of mDCs, it was higher in control group and the non
      SKD group compared to SKD group, while in control group it was higher than both
      HBeAg positive group and negative group. The number of pDCs in control group and
      chronic hepatitis B group were higher than HBVcarrier group, and it was higher in
      control group than both immune tolerance group and inactive group, while in
      immune clearance group it was higher than immune tolerance group and inactve
      group. The number of mDCs in control group and immune clearance group were higher
      than that of immune tolerance group. There was an obvious correlation between TCM
      syndromes and immune function in HBV infected patients, the number of pDCs and
      mDCs of the SKD group was lower than that in non-SKD group. These results provide
      a new insight into scientific evidence that TCM probably be based.

PMID- 29168887
TI  - Implications of WHO Guideline on Sugars for dental health professionals.
AB  - The burden of oral disease is high in populations across the world. This is
      because of high consumption of free sugars. The WHO Guideline on Sugars Intake
      for Adults and Children recommended limiting free sugars to no more than 5%
      energy intake to protect oral health throughout the life-course. The objectives
      of this paper are to consider the implications of the Guideline for dental health
      practice and to advocate use of the common risk factor approach when providing
      dietary advice. As part of a broad range of actions needed to reduce free sugars
      intake, improved education for dental health professionals and supporting
      patients to eat less free sugars are key actions for the dental profession. All
      dental health professionals should have the skills and confidence to provide
      their patients with healthier eating advice, including how to limit free sugars
      intake. It is therefore important that dental health professionals receive
      adequate education in diet and nutrition, and there is a need for dental
      educational regulating bodies to define the content of the dental curriculum with
      respect to nutrition. All patients, or their parents or carers, should receive
      dietary advice to reduce free sugars within the context of a healthy diet for the
      prevention of all NCDs. Dietary advice should: (i) focus on reducing the amount
      of free sugars consumed; (ii) be tailored according to the patient's body mass
      status (eg underweight, overweight, normal weight); (iii) encourage the
      consumption of fresh fruits and vegetables, nuts, seeds, and wholegrain starch
      rich foods; (iv) discourage the consumption of foods high in saturated fat and
      salt; and (v) discourage the consumption of all drinks containing free sugars.
      The dental health professional has an opportunity to support patients to reduce
      their intake of free sugars-such advice and support will have positive impacts
      beyond the mouth.

PMID- 29168888
TI  - Apparent seronegative maternal shingles with post-natal mother-to-baby
      transmission of varicella zoster virus.
AB  - We present an unusual case of varicella zoster (VZ) virus IgG negative, yet
      clinically apparent, maternal shingles, which prompted the administration of VZ
      immunoglobulin to the newborn. The mother had no previous VZ vaccination. Eleven
      days later the baby developed a primary VZ infection, with only mild disease,
      likely as a result of the VZ immunoglobulin. The variable sensitivity of VZV IgG
      specific assays is well-recognized. Thus, the ability of this particular VZV IgG
      assay to detect both maternal and infant VZV IgG, post-natally, suggests that the
      earlier VZV IgG negative results were due to lower circulating levels of maternal
      antibody.

PMID- 29168889
TI  - Acute viral infections of the central nervous system, 2014-2016, Greece.
AB  - In order to investigate the viral etiology of acute infections of central nervous
      system (CNS), multiplex and single PCRs combined with serology for arboviruses
      were applied on samples from 132 hospitalized patients in Greece during May 2014
      December 2016. A viral pathogen was detected in 52 of 132 (39.4%) cases with
      acute CNS infection. Enteroviruses predominated (15/52, 28.8%), followed by West
      Nile virus (9/52, 17.3%). Phleboviruses, varicella-zoster virus, and Epstein-Barr
      virus accounted for 15.4%, 13.5%, and 11.5% of the cases, respectively. The study
      gives an insight into the etiology of viral CNS infections in a Mediterranean
      country, where arboviruses should be included in the differential diagnosis of
      acute CNS infections.

PMID- 29168890
TI  - Toward improved analysis of concentration data: Embracing nondetects.
AB  - Various statistical tests on concentration data serve to support decision-making
      regarding characterization and monitoring of contaminated media, assessing
      exposure to a chemical, and quantifying the associated risks. However, the
      routine statistical protocols cannot be directly applied because of challenges
      arising from nondetects or left-censored observations, which are concentration
      measurements below the detection limit of measuring instruments. Despite the
      existence of techniques based on survival analysis that can adjust for
      nondetects, these are seldom taken into account properly. A comprehensive review
      of the literature showed that managing policies regarding analysis of censored
      data do not always agree and that guidance from regulatory agencies may be
      outdated. Therefore, researchers and practitioners commonly resort to the most
      convenient way of tackling the censored data problem by substituting nondetects
      with arbitrary constants prior to data analysis, although this is generally
      regarded as a bias-prone approach. Hoping to improve the interpretation of
      concentration data, the present article aims to familiarize researchers in
      different disciplines with the significance of left-censored observations and
      provides theoretical and computational recommendations (under both frequentist
      and Bayesian frameworks) for adequate analysis of censored data. In particular,
      the present article synthesizes key findings from previous research with respect
      to 3 noteworthy aspects of inferential statistics: estimation of descriptive
      statistics, hypothesis testing, and regression analysis. Environ Toxicol Chem
      2018;37:643-656. (c) 2017 SETAC.

PMID- 29168891
TI  - Effects of sediment resuspension on the oxidation of acid-volatile sulfides and
      release of metals (iron, manganese, zinc) in Pescadero estuary (CA, USA).
AB  - Bar-built estuaries are unique ecosystems characterized by the presence of a
      sandbar barrier, which separates the estuary from the ocean for extended periods
      and can naturally reopen to the ocean with heavy rainfall and freshwater inflows.
      The physical effects associated with the transition from closed to open state,
      specifically water mixing and sediment resuspension, often indirectly worsen
      water quality conditions and are suspected to drive near-annual fish kills at the
      Pescadero estuary in northern California. The effects of sediment acid-volatile
      sulfide (AVS) oxidation, specifically oxygen depletion, acidification, and metal
      release, are believed to aggravate water conditions for fish but remain poorly
      understood. We performed slurry incubations containing sediment from 4 sites in
      the Pescadero estuary, representing a gradient from the Pacific Ocean to
      freshwater tributaries. We measured near-maximum rates of aqueous hydrogen
      sulfide oxidation, sediment AVS oxidation, sulfate production, and acidification,
      as well as near-maximum release rates of iron (Fe), manganese (Mn), and zinc (Zn)
      to the water column. We estimated AVS oxidation rates of 8 to 21 mmol S kg-1  d-1
      , which were 3 orders of magnitude higher than aqueous hydrogen sulfide oxidation
      rates, 6 to 26 MUmol S kg-1  d-1 . We suggest that aqueous hydrogen sulfide
      cannot be responsible for the observed kills because of low concentrations and
      minimal oxidative effects on pH and metal concentrations. However, the oxidative
      effects of AVS are potentially severe, decreasing pH to strongly acidic levels
      and releasing aqueous Fe, Mn, and Zn concentrations up to 11.2 mM, 0.46 mM, and
      88 MUM, respectively, indicating a potential role in worsening water conditions
      for fish in the Pescadero estuary. Environ Toxicol Chem 2018;37:993-1006. (c)
      2017 SETAC.

PMID- 29168893
TI  - Oral tolerance modulates the skin transcriptome in mice with induced atopic
      dermatitis.
AB  - Defective gut immune reactions have been implicated in the development of atopic
      dermatitis (AD), whereas oral tolerance (OT), that is, the immune
      unresponsiveness induced by oral antigen administration, protects mice against
      AD. To investigate this protective role of OT, the transcriptomic profiles of
      skin were obtained by RNA sequencing from mice that were epicutaneously
      sensitized, orally tolerized prior to epicutaneous sensitization, or neither
      (control). Oral tolerance inhibited the upregulation of keratin- and allergic
      inflammation-associated genes that occurred in the epicutaneously sensitized
      group. Compared to the controls, mice that were orally tolerized and
      epicutaneously sensitized showed an upregulation of genes that regulate
      inflammation or keratinocyte differentiation. Knocking down two of those genes,
      SCGB1A1 and TSC22D3, upregulated Th2 inflammatory mediators and downregulated a
      cornified cell envelope-related gene. Based on our findings, OT may protect skin
      against allergic inflammation by promoting the expression of genes that regulate
      Th2 inflammatory responses and skin barrier function.

PMID- 29168892
TI  - Functional properties of dopamine transporter oligomers after copper linking.
AB  - Although it is universally accepted that dopamine transporters (DATs) exist in
      monomers, dimers and tetramers (i.e. dimers of dimers), it is not known whether
      the oligomeric organization of DAT is a prerequisite for its ability to take up
      dopamine (DA), or whether each DAT protomer, the subunit of quaternary structure,
      functions independently in terms of DA translocation. In this study, copper
      phenanthroline (CuP) was used to selectively target surface DAT: increasing
      concentrations of CuP gradually cross-linked natural DAT dimers in LLC-PK1 cells
      stably expressing hDAT and thereby reduced DA uptake functionality until all
      surface DATs were inactivated. DATs that were not cross-linked by CuP showed
      normal DA uptake with DA Km at ~ 0.5 MUM and DA efflux with basal and amphetamine
      induced DA efflux as much as control values. The cocaine analog 2beta
      carbomethoxy-3beta-[4-fluorophenyl]-tropane (CFT) was capable to bind to copper
      cross-linked DATs, albeit with an affinity more than fivefold decreased (Kd of
      CFT = 109 nM after cross-linking vs 19 nM before). A kinetic analysis is offered
      describing the changing amounts of dimers and monomers with increasing [CuP],
      allowing the estimation of dimer functional activity compared with a DAT monomer.
      Consonant with previous conclusions for serotonin transporter and NET that only
      one protomer of an oligomer is active at the time, the present data indicated a
      functional activity of the DAT dimer of 0.74 relative to a monomer.

PMID- 29168894
TI  - Fluid mixing in droplet-based microfluidics with T junction and convergent
      divergent sinusoidal microchannels.
AB  - To explore and utilize the advantages of droplet-based microfluidics,
      hydrodynamics, and mixing process within droplets traveling though the T junction
      channel and convergent-divergent sinusoidal microchannels are studied by
      numerical simulations and experiments, respectively. In the T junction channel,
      the mixing efficiency is significantly influenced by the twirling effect, which
      controls the initial distributions of the mixture during the droplet formation
      stage. Therefore, the internal recirculating flow can create a convection
      mechanism, thus improving mixing. The twirling effect is noticeably influenced by
      the velocity of the continuous phase; in the sinusoidal channel, the Dean
      vortices and droplet deformation are induced by centrifugal force and alternative
      velocity gradient, thus enhancing the mixing efficiency. The best mixing occurred
      when the droplet size is comparable with the channel width. Finally, we propose a
      unique optimized structure, which includes a T junction inlet joined to a
      sinusoidal channel. In this structure, the mixing of fluids in the droplets
      follows two routes: One is the twirling effect and symmetric recirculation flow
      in the straight channel. The other is the asymmetric recirculation and droplet
      deformation in the winding and variable cross-section. Among the three
      structures, the optimized structure has the best mixing efficiency at the
      shortest mixing time (0.25 ms). The combination of the twirling effect, variable
      cross-section effect, and Dean vortices greatly intensifies the chaotic flow.
      This study provides the insight of the mixing process and may benefit the design
      and operations of droplet-based microfluidics.

PMID- 29168895
TI  - Epigenetics as a Driver of Developmental Origins of Health and Disease: Did We
      Forget the Fathers?
AB  - What are the effects of our environment on human development and the next
      generation? Numerous studies have provided ample evidence that a healthy
      environment and lifestyle of the mother is important for her offspring.
      Biological mechanisms underlying these environmental influences have been
      proposed to involve alterations in the epigenome. Is there enough evidence to
      suggest a similar contribution from the part of the father? Animal models provide
      proof of a transgenerational epigenetic effect through the paternal germ line,
      but can this be translated to humans? To date, literature on fathers is scarce.
      Human studies do not always incorporate appropriate tools to evaluate paternal
      influences or epigenetic effects. In reviewing the literature, I stress the need
      to explore and recognize paternal contributions to offspring's health within the
      Developmental Origins of Health and Disease hypothesis, and coin this new concept
      the Paternal Origins of Health and Disease paradigm (POHaD). A better
      understanding of preconceptional origins of disease through the totality of
      paternal exposures, or the paternal exposome, will provide evidence-based public
      health recommendations for future fathers.

PMID- 29168896
TI  - Healing of self-inflicted thermal injury of palatal mucosa by low-level laser
      therapy.
AB  - Self-inflicted injury to oral mucosa is a rare entity. These injuries can be
      premeditated, accidental, or can result from an abnormal habit. These uncommon
      gingival injuries can sometimes test the clinician's diagnostic abilities as well
      as treatment planning skills. In conventional treatment, removal of etiology and
      application of topical drugs is usually sufficient for healing. However, some
      cases require alternative or adjunctive wound healing methods. Low-level laser
      therapy (LLLT) has been reported to be effective in pain management and
      improvement in wound healing through promotion, fortification, and commissioning
      of cellular cycle to generate productive and substitute cells. This report
      presents a case of 25-year-old female with complaints of a painful, nonhealing
      wound on the palate for last 6 months. She had an unusual habit of keeping
      burning matchsticks in her mouth. Although she had quit the habit 2 months ago
      after psychiatric counseling, the wound on her palate did not show any
      improvement in symptoms. Based on the history and clinical findings, diagnosis of
      chronic wound by self-inflicted thermal injury was made. LLLT was administered on
      the wound every 48 hours for next 10 days. The burn wound healed completely after
      five applications of LLLT.

PMID- 29168897
TI  - Early socioeconomic conditions and severe tooth loss in middle-aged Costa Ricans.
AB  - OBJECTIVE: A wide literature shows a strong social gradient in tooth loss
      according to income, education and occupation, in both developed and developing
      countries. It has been shown associations between tooth loss and parental
      education and occupation, independently of adult conditions. To explore the role
      of early socioeconomic circumstances on tooth loss, we used a lifecourse model.
      We analysed the direct and indirect links between early socioeconomic conditions
      and severe adult tooth loss. METHODS: We used the Costa Rican Longevity and
      Healthy Aging Study 1945-1955 Retirement Cohort, a nationally representative
      longitudinal survey of Costa Rican residents born between 1945 and 1955. We used
      imputed data on 2796 individuals. Principal component analyses were run to
      integrate measures approaching the material circumstances during childhood and
      adulthood. We additionally examined the role of adult health behaviours and
      education level as potential mediators in the multivariable regression. RESULTS:
      Early socioeconomic conditions were found strongly associated with severe tooth
      loss; 72.4% of the people who experienced the most deprived socioeconomic
      conditions during childhood (quartile 1) had severe tooth loss at the time of the
      interview; vs 43.3% in quartile 4 (most advantaged). This link diminished after
      adjustment for adult mediators. However, it remained a significant determinant of
      severe tooth loss in the final model. CONCLUSION: The lifecourse model allowed to
      highlight that early socioeconomic conditions could have long-term consequences
      on severe tooth loss in middle ages via both direct and indirect mechanisms.

PMID- 29168898
TI  - Association of p16 (CDKN2A) polymorphisms with the development of HPV16-related
      precancerous lesions and cervical cancer in the Greek population.
AB  - The tumor suppressor protein p16 plays a fundamental role in cell cycle
      regulation and exerts a protective effect against tumor growth. Two different
      polymorphisms at positions 540 and 580 at the 3'UTR of exon 3 of p16 gene are
      implicated in several types of cancer, while their role in cervical cancer
      development remains rather vague. In the present study, we investigated for the
      impact of p16 genotypes/haplotypes on patients' vulnerability to cervical disease
      and examined whether these factors can be used as progression markers in the
      Greek population. A total of 96 HPV16 positive samples and histologically
      confirmed as LSIL (42 samples), HSIL (44 samples), and cervical cancer cases (10
      samples) along with 50 control cases were tested. The identification of p16
      polymorphisms was performed by PCR-RFLP methodology. The present analysis
      revealed that women with p16 540 CG/GG genotype are at a 2.7-fold higher risk of
      developing HPV16-associated HSIL (OR = 2.7, 95%CI: 1.01-6.6, P = 0.028). The G
      allele can be regarded as a risk factor of developing HSIL in the Greek
      population (OR = 2.7, 95%CI: 1.2-5.9, P = 0.012). Moreover, p16 polymorphism
      C580T is not associated with the growth of cervical lesion in Greek patients,
      while 540G/580C haplotype can be regarded as a risk haplotype of developing HSIL
      (OR = 3.67, 95%CI: 1.56-8.6, P = 0.0019). Our results demonstrated that p16 C540G
      polymorphism influence patients' susceptibility to more severe dysplasia and
      consequently this polymorphism could potentially emerge as a valuable biomarker
      for HSIL development in the Greek population.

PMID- 29168899
TI  - Global scales for cognitive screening in Parkinson's disease: Critique and
      recommendations.
AB  - BACKGROUND: Cognitive impairment is a common nonmotor manifestation of
      Parkinson's disease, with deficits ranging from mild cognitive difficulties in 1
      or more of the cognitive domains to severe dementia. The International Parkinson
      and Movement Disorder Society commissioned the assessment of the clinimetric
      properties of cognitive rating scales measuring global cognitive performance in
      PD to make recommendations regarding their use. METHODS: A systematic literature
      search was conducted to identify the scales used to assess global cognitive
      performance in PD, and the identified scales were reviewed and rated as
      "recommended," "recommended with caveats," "suggested," or "listed" by the panel
      using previously established criteria. RESULTS: A total of 12 cognitive scales
      were included in this review. Three scales, the Montreal Cognitive Assessment,
      the Mattis Dementia Rating Scale Second Edition, and the Parkinson's Disease
      Cognitive Rating Scale, were classified as "recommended." Two scales were
      classified as "recommended with caveats": the Mini-Mental Parkinson, because of
      limited coverage of executive abilities, and the Scales for Outcomes in
      Parkinson's Disease-Cognition, which has limited data on sensitivity to change.
      Six other scales were classified as "suggested" and 1 scale as "listed."
      CONCLUSIONS: Because of the existence of "recommended" scales for assessment of
      global cognitive performance in PD, this task force suggests that the development
      of a new scale for this purpose is not needed at this time. However, global
      cognitive scales are not a substitute for comprehensive neuropsychological
      testing. (c) 2017 International Parkinson and Movement Disorder Society.

PMID- 29168900
TI  - Naphthodithiophene-Based Nonfullerene Acceptor for High-Performance Organic
      Photovoltaics: Effect of Extended Conjugation.
AB  - Naphtho[1,2-b:5,6-b']dithiophene is extended to a fused octacyclic building
      block, which is end capped by strong electron-withdrawing 2-(5,6-difluoro-3-oxo
      2,3-dihydro-1H-inden-1-ylidene)malononitrile to yield a fused-ring electron
      acceptor (IOIC2) for organic solar cells (OSCs). Relative to naphthalene-based
      IHIC2, naphthodithiophene-based IOIC2 with a larger pi-conjugation and a stronger
      electron-donating core shows a higher lowest unoccupied molecular orbital energy
      level (IOIC2: -3.78 eV vs IHIC2: -3.86 eV), broader absorption with a smaller
      optical bandgap (IOIC2: 1.55 eV vs IHIC2: 1.66 eV), and a higher electron
      mobility (IOIC2: 1.0 * 10-3 cm2 V-1 s-1 vs IHIC2: 5.0 * 10-4 cm2 V-1 s-1 ). Thus,
      IOIC2-based OSCs show higher values in open-circuit voltage, short-circuit
      current density, fill factor, and thereby much higher power conversion efficiency
      (PCE) values than those of the IHIC2-based counterpart. In particular, as-cast
      OSCs based on FTAZ: IOIC2 yield PCEs of up to 11.2%, higher than that of the
      control devices based on FTAZ: IHIC2 (7.45%). Furthermore, by using 0.2% 1,8
      diiodooctane as the processing additive, a PCE of 12.3% is achieved from the
      FTAZ:IOIC2-based devices, higher than that of the FTAZ:IHIC2-based devices
      (7.31%). These results indicate that incorporating extended conjugation into the
      electron-donating fused-ring units in nonfullerene acceptors is a promising
      strategy for designing high-performance electron acceptors.

PMID- 29168901
TI  - Oxybuprocaine for apraxia of lid opening in Parkinson's disease: A placebo
      controlled pilot trial.

PMID- 29168902
TI  - An in-situ thermally regenerated air purifier for indoor formaldehyde removal.
AB  - Formaldehyde is a common indoor pollutant that is an irritant and has been
      classified as carcinogen to humans. Adsorption technology is safe and stable and
      removes formaldehyde efficiently, but its short life span and low adsorption
      capacity limit its indoor application. To overcome these limitations, we propose
      an in-situ thermally regenerated air purifier (TRAP) which self-regenerates as
      needed. This purifier has four working modes: cleaning mode, regeneration mode,
      exhaust mode, and outdoor air in-take mode, all of which are operated by valve
      switching. We developed a real-scale TRAP prototype with activated carbon as
      adsorbent. The experimental testing showed that the regeneration ratios for
      formaldehyde of TRAP were greater than 90% during 5 cycles of adsorption
      regeneration and that through the 5 cycles, there was no damage to the adsorption
      material as confirmed by scanning electron microscope (SEM) and Brunauer-Emmett
      Teller (BET) tests. The total energy consumption by the prototype for purifying
      1000 m3 indoor air was 0.26 kWh. This in-situ thermal-regeneration method can
      recover the purifier's adsorption ability through at least five cycles.

PMID- 29168903
TI  - Black-Phosphorus-Based Orientation-Induced Diodes.
AB  - Despite many decades of research of diodes, which are fundamental components of
      electronic and photoelectronic devices with p-n or Schottky junctions using bulk
      or 2D materials, stereotyped architectures and complex technological processing
      (doping and multiple material operations) have limited future development. Here,
      a novel rectification device, an orientation-induced diode, assembled using only
      few-layered black phosphorus (BP) is investigated. The key to its realization is
      to utilize the remarkable anisotropy of BP in low dimensions and change the
      charge-transport conditions abruptly along the different crystal orientations.
      Rectification ratios of 6.8, 22, and 115 can be achieved in cruciform BP, cross
      stacked BP junctions, and BP junctions stacked with vertical orientations,
      respectively. The underlying physical processes and mechanisms can be explained
      using "orientation barrier" band theory. The theoretical results are
      experimentally confirmed using localized scanning photocurrent imaging. These
      orientation-induced optoelectronic devices open possibilities for 2D anisotropic
      materials with a new degree of freedom to improve modulation in diodes.

PMID- 29168905
TI  - Neonatal intensive care at 22-24 weeks' gestation: How low should we go?

PMID- 29168906
TI  - Recurrent Mycobacterium fortuitum insulin injection site abscesses.

PMID- 29168904
TI  - APOE, thought disorder, and SPARE-AD predict cognitive decline in established
      Parkinson's disease.
AB  - BACKGROUND: People with PD are at high risk of developing cognitive impairment
      and dementia. Cross-sectional studies have identified candidate biomarkers
      associated with cognitive decline. However, longitudinal studies on this topic
      are rarer, and few have investigated the use of biomarker panels encompassing
      multiple modalities. The objective of this study was to find baseline predictors
      of cognitive decline in longitudinally followed, nondemented Parkinson's disease
      patients. METHODS: We performed a prospective cohort study of 100 PD patients
      with a median disease duration of 6.4 years. All participants were nondemented at
      baseline. We examined 16 baseline biomarkers from clinical, genetic, biochemical,
      and MRI-based imaging modalities for their association with longitudinal
      cognitive decline for up to 8 years. We investigated biomarkers individually, as
      well as in a multivariate linear mixed-effects model encompassing multimodal
      biomarkers, with change in the Mattis Dementia Rating Scale-2 over time as the
      primary outcome. Annual consensus process-derived cognitive diagnosis was used
      for Cox proportional hazards modeling of risk for cognitive decline. RESULTS: In
      multivariate analysis, the presence of the APOE E4 allele, thought disorder, and
      an Alzheimer's disease pattern of brain atrophy (spatial pattern of abnormality
      for recognition of early Alzheimer's disease index) best predicted cognitive
      decline, with APOE E4 genotype exerting the greatest effect. The presence of the
      APOE E4 allele was associated with a 3.5 times higher risk of worsening cognitive
      diagnosis over time (HR, 3.53; 95% CI, 1.52-8.24; P < 0.05). The APOE genotype
      effect was not specific to any Mattis Dementia Rating Scale-2 domain.
      CONCLUSIONS: Our results confirm the importance of Alzheimer's disease biomarkers
      as risk factors for cognitive decline in established Parkinson's disease. (c)
      2017 International Parkinson and Movement Disorder Society.

PMID- 29168907
TI  - Expanding the Toolbox of Photoswitches for DNA Nanotechnology Using
      Arylazopyrazoles.
AB  - Photoregulation is among the most promising tools for development of dynamic DNA
      nanosystems, due to its high spatiotemporal precision, biocompatibility, and ease
      of use. So far, azobenzene and its derivatives have shown high potential in
      photocontrolling DNA duplex hybridization by light-dependent photoisomerization.
      Despite many recent advances, obtaining sufficiently high photoswitching
      efficiency under conditions more suitable for work with DNA nanostructures are
      challenging. Here we introduce a pair of arylazopyrazoles as new photoswitches
      for efficient and reversible control of DNA hybridization achieved even at room
      temperature with a low number of required modifications. Their photophysical
      properties in the native state and in DNA strands result in near-quantitative
      isomerization rates by irradiation with UV and orange light. To demonstrate the
      applicability of these photoswitches, we have successfully applied one of them to
      open and close a DNA hairpin by light at room temperature.

PMID- 29168908
TI  - The Rickiols: 20-, 22-, and 24-membered Macrolides from the Ascomycete Hypoxylon
      rickii.
AB  - In preceding studies the neotropical ascomycete Hypoxylon rickii turned out to be
      a prolific source of new secondary metabolites, considering that we had obtained
      terpenoids with five different scaffolds along with a series of terphenyls. From
      the mycelial extracts of a 70 L scale fermentation of this strain we additionally
      isolated nine new macrolides (1-9) by RP-HPLC. The planar structures were
      elucidated by NMR spectroscopy complemented by HR-ESIMS. The relative
      configurations were assigned by J-based configuration analyses and confirmed by
      Kishi's Universal Database. Subsequently, the absolute configurations were
      assigned by Mosher's method using the shift analysis of a tetra-MTPA derivative.
      For rickiol A (1) and E (5) we observed transesterification of 20-membered ring
      structures to 22-membered isomers rickiol A2 (6) and E2 (7), and to 24-membered
      isomers rickiol A3 (8) and rickiol E3 (9), respectively. Cytotoxic effects and
      moderate antibiotic activity against Gram-positive bacteria were observed for 1-8
      and 1-6 and 8, respectively. The total synthesis of rickiol E3 (9) established
      easier access to these compounds.

PMID- 29168909
TI  - In Situ Generated Ruthenium-Arene Catalyst for Photoactivated Ring-Opening
      Metathesis Polymerization through Photolatent N-Heterocyclic Carbene Ligand.
AB  - 1,3-Bis(mesityl)imidazolium tetraphenylborate (IMesH+ BPh4- ) can be synthesized
      in one step by anion metathesis between the corresponding imidazolium chloride
      and sodium tetraphenylborate. In the presence of 2-isopropylthioxanthone
      (sensitizer), an IMes N-heterocyclic carbene (NHC) ligand can be photogenerated
      under irradiation at 365 nm through coupled electron/proton transfer reactions.
      By combining this tandem NHC photogenerator system with metathesis inactive
      [RuCl2 (p-cymene)]2 precatalyst, the highly active RuCl2 (p-cymene)(IMes) complex
      can be formed in situ, enabling a complete ring-opening metathesis polymerization
      (ROMP) of norbornene in the matter of minutes at room temperature. To the best of
      our knowledge, this is the first example of a photogenerated NHC. Its
      exploitation in photoROMP has resulted in a simplified process compared to
      current photocatalysts, because only stable commercial or easily synthesized
      reagents are required.

PMID- 29168910
TI  - Parental Immunisation Needs and Attitudes Survey in paediatric hospital clinics
      and community maternal and child health centres in Melbourne, Australia.
AB  - AIM: Despite Australia's high vaccination rates, an estimated 3.3% of children
      are under-vaccinated due to vaccine refusal and the proportion of parents with
      concerns is unclear. Amongst Australian parents, we aimed to determine the
      prevalence of vaccine concerns, resources and health-care providers (HCPs)
      accessed and satisfaction with these resources in two different settings. We also
      aimed to identify relationships between the level of vaccine concern, socio
      economic status and vaccine uptake. METHODS: Parents of children under 5 years
      attending general paediatric clinics in a tertiary paediatric hospital (n =
      301/398, 76%) and children under 19 months attending community maternal child
      health centres (n = 311/391, 81%) completed the survey. Vaccination status was
      obtained from the Australian Childhood Immunisation Register. RESULTS: Despite
      high support for vaccination (98%, confidence interval (CI) 97-99), 43% of
      parents reported vaccine concerns (CI 40-47) including the number of vaccines
      given in the first 2 years (25%, CI 22 to 29), vaccine ingredients (22%, CI 19
      25), allergies (18%, CI 15-21), weakening of the immune system (17%, CI 14-20)
      and autism (11%, CI 8-13). HCPs were the most commonly accessed and trusted
      information source. In all, 23% of parents reported insufficient knowledge to
      make good vaccination decisions (CI 20-26). There was little evidence of an
      association between parental vaccine acceptance or socio-economic status and
      vaccination status. CONCLUSIONS: Despite high support for vaccines, nearly half
      of Australian parents have some concerns and a quarter lack vaccine decision
      making confidence regarding childhood vaccines. Parents frequently access and
      report high trust in HCPs, who are best placed to address parental vaccine
      concerns through provision of clear information, using effective communication
      strategies. Further research in more highly hesitant populations is required to
      determine the relationship between the level and nature of vaccination concerns
      and vaccine uptake.

PMID- 29168911
TI  - Pre-operative parameters do not reliably identify post-operative respiratory risk
      in children undergoing adenotonsillectomy.
AB  - AIM: Adenotonsillectomy is performed in children with recurrent tonsillitis or
      obstructive sleep apnoea. Children at risk of post-operative respiratory
      complications are recommended to be monitored in paediatric intensive care unit
      (PICU). The aim of the study is to review the risk factors for post-operative
      complications and admissions to PICU. METHODS: A review of medical records of
      children who underwent adenotonsillectomy between January 2011 and December 2014
      was performed. Association between demographic variables and post-operative
      complications were examined using chi-square and Mann-Whitney tests. RESULTS: A
      total of 214 children were identified, and of these, 19 (8.8%) experienced post
      operative complications. Six children (2.8%) had respiratory complications:
      hypoxaemia in four and laryngospasm requiring reintubation in a further two. Both
      of the latter patients were extubated upon arrival to PICU and required no
      escalation of therapy. A total of 13 (6.1%) children had non-respiratory
      complications: 8 (3.7%) had infection and 5 (2.3%) had haemorrhage. A total of 26
      (12.1%) children were electively admitted to PICU and mean stay was 19.5 (SD +/-
      13) h. No association between demographic characteristics, comorbid conditions or
      polysomnographic parameters and post-operative complications were noted. A total
      of 194 (90.7%) children stayed only one night in hospital (median 1 day, range 1
      5 days). CONCLUSION: The previously identified risk factors and criteria for PICU
      admission need revision, and new recommendations are necessary.

PMID- 29168912
TI  - Zinc/Nickel-Doped Hollow Core-Shell Co3 O4 Derived from a Metal-Organic Framework
      with High Capacity, Stability, and Rate Performance in Lithium/Sodium-Ion
      Batteries.
AB  - Transition-metal oxides are one of the most promising anode materials for energy
      storage in lithium- and sodium-ion batteries (LIBs and NIBs, respectively). To
      improve the electrochemical performance of metal oxides (e.g., Co3 O4 ), such as
      capacity and cyclability, a convenient strategy (with a metal-organic framework
      as a template) is introduced to generate Zn- or Ni-doped Co3 O4 . The obtained
      hollow core-shell nanosized Co3 O4 (denoted as Zn/Ni-Co-Oxide) derived from
      pyrolyzing zinc or nickel co-doped ZIF-67 (Co(mIm)2 ; mIm=methylimidazole) shows
      a drastically enhanced capacity of 1300 mAh g-1 at a high current density of 5000
      mA g-1 , compared with that of pristine cobalt oxide (800 mAh g-1 ) in LIBs. A
      zinc-doped Zn-Co-Oxide demonstrates a stable capacity of 1600 mAh g-1 at 1000 mA
      g-1 for 700 cycles and an excellent performance in full coin cells (cycled with
      LiNi0.5 Co0.3 Mn0.2 O2 ). Moreover, NIB tests show a stable capacity of 300 mAh g
      1 for more than 250 cycles.

PMID- 29168913
TI  - Synthesis, characterization, and biological properties of composites of
      hydroxyapatite and hexagonal boron nitride.
AB  - Hydroxyapatite (HA), obtained from bovine bones, was successfully reinforced with
      hexagonal boron nitrite (h-BN). h-BN/HA composites, with BN content up to 1.5 wt
      %, were sintered at various temperatures between 1000 and 1300 degrees C, in air.
      Well-sintered samples were obtained after sintering at 1200 and 1300 degrees C.
      The presence of h-BN contributed to dense, fine, and well-crystallized
      microstructure. The results of X-ray diffraction analysis and FT-IR spectroscopy
      showed that the produced composites comprised biphasic beta-TCP/HCA (HCA:
      carbonate partially substituted HA). High values of mechanical properties were
      achieved, namely compression strength 155 MPa for the sample 0.5% h-BN/HA and
      Vickers microhardness of 716 HV for the samples 1.5% h-BN/HA, both sintered at
      1300 degrees C. U2OS human bone osteosarcoma proliferation and cell viability
      showed no adverse effect in the presence of h-BN/HA, suggesting the potential use
      of the produced materials as safe biomaterials in bone tissue engineering. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2384
      2392, 2018.

PMID- 29168914
TI  - Shortfall of B3LYP in Reproducing NMR JCH Couplings in Some Isomeric Epoxy
      Structures with Strong Stereoelectronic Effects: A Benchmark Study on DFT
      Functionals.
AB  - Unprecedented scatter plots of calculated versus measured NMR 2,3 JCH coupling
      constants in six densely oxygen functionalized epoxides are found with some B3LYP
      protocols, an effect attributed to stereoelectronic effects. Hence, 26 other
      exchange-correlation density functionals (xc DFs) are benchmarked in this work.
      Very good results are achieved with mPW1PW91 and PBE0 in conjunction with the pcJ
      1 basis set (BS) of moderate size. A thorough statistical analysis of 53
      relationships between the predicted and observed 2,3 JCH datasets is presented.
      The effects of some xc DFs, including their x and c parts, and BSs on the
      calculation results are discussed, also in the context of DFT modeling of
      electron-density distributions. Moreover, related 1 JCH datasets predicted with
      11 different DF methods are considered and compared with the experimental data.
      Finally, some proposals for further improvement of existing DFs based on the
      available n JCH (n=1-3) values are briefly outlined, in line with recent results
      on the DFT electron densities.

PMID- 29168915
TI  - A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2
      Diabetes Mellitus.
AB  - Neutrophil dysfunction is strongly linked to type 2 diabetes mellitus (T2DM)
      pathophysiology, but the prognostic potential of neutrophil biomarkers remains
      largely unexplored due to arduous leukocyte isolation methods. Herein, a novel
      integrated microdevice is reported for single-step neutrophil sorting and
      phenotyping (chemotaxis and formation of neutrophil extracellular traps
      (NETosis)) using small blood volumes (fingerprick). Untouched neutrophils are
      purified on-chip from whole blood directly using biomimetic cell margination and
      affinity-based capture, and are exposed to preloaded chemoattractant or NETosis
      stimulant to initiate chemotaxis or NETosis, respectively. Device performance is
      first characterized using healthy and in vitro inflamed blood samples (tumor
      necrosis factor alpha, high glucose), followed by clinical risk stratification in
      a cohort of subjects with T2DM. Interestingly, "high-risk" T2DM patients
      characterized by severe chemotaxis impairment reveal significantly higher C
      reactive protein levels and poor lipid metabolism characteristics as compared to
      "low-risk" subjects, and their neutrophil chemotaxis responses can be mitigated
      after in vitro metformin treatment. Overall, this unique and user-friendly
      microfluidics immune health profiling strategy can significantly aid the
      quantification of chemotaxis and NETosis in clinical settings, and be further
      translated into a tool for risk stratification and precision medicine methods in
      subjects with metabolic diseases such as T2DM.

PMID- 29168916
TI  - Fabrication, characterization, and biocompatibility assessment of a novel
      elastomeric nanofibrous scaffold: A potential scaffold for soft tissue
      engineering.
AB  - With regard to flexibility and strength properties requirements of soft
      biological tissue, elastomeric materials could be more beneficial in soft tissue
      engineering applications. The present work investigates the use of an elastic
      polymer, (polycaprolactone fumarate [PCLF]), for fabricating an electrospun
      scaffold. PCLF with number-average molecular weight of 13,284 g/mol was
      synthetized, electrospun PCLF:polycaprolactone (PCL) (70:30) nanofibrous
      scaffolds were fabricated and a novel strategy (in situ photo-crosslinking along
      with wet electrospinning) was applied for crosslinking of PCLF in the structure
      of PCLF:PCL nanofibers was presented. Sol fraction results, Fourier-transform
      infrared spectroscopy, and mechanical tests confirmed occurrence of crosslinking
      reaction. Strain at break and Young's modulus of crosslinked PCLF:PCL nanofibers
      fabricated was found to be 114.5 +/- 3.9% and 0.6 +/- 0.1 MPa, respectively, and
      dynamic mechanical analysis results revealed elasticity of nanofibers. MTS assay
      showed biocompatibility of PCLF:PCL (70:30) nanofibrous scaffolds. Our overall
      results showed that electrospun PCLF:PCL nanofibrous scaffold could be considered
      as a candidate for further in vitro and in vivo experiments and its application
      for engineering of soft tissues subjected to in vivo cyclic mechanical stresses.
      (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B:
      2371-2383, 2018.

PMID- 29168917
TI  - In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4 
      TAT Nanoprobes.
AB  - Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat
      residual lesions after glioma surgery. However, the fate of the adoptively
      transferred T-cells in vivo is unclear, hampering the understanding of this
      emerging therapy. Thus, it is highly desirable to develop noninvasive and
      quantitative in vivo tracking of these T-cells to glioma for better
      identification of the migratory fate and to provide objective evaluation of
      outcomes of adoptive T-cell immunotherapy targeting glioma. In this work,
      ultrasmall T1 MR-based nanoprobes, NaGdF4 -TAT, as molecular probes with high
      longitudinal relaxivity (8.93 mm-1 s-1 ) are designed. By means of HIV-1
      transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled
      with the NaGdF4 -TAT nanoprobes without any measurable side effects on the
      labeled T-cells, which is remarkably superior to that of the control fluorescein
      isothiocyanate-NaGdF4 concerning labeling efficacy. Labeled adoptive T-cell
      clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h
      after intravenous infusion of 107 labeled T-cells by T1 -weighted MR imaging.
      Both in vitro and in vivo experiments show that the NaGdF4 -TAT nanoprobes
      labeling of T-cells may be a promising method to track adoptive T-cells to
      improve our understanding of the pathophysiology in adoptive immunotherapy for
      gliomas.

PMID- 29168918
TI  - Nano-Biohybrids: In Vivo Synthesis of Metal-Organic Frameworks inside Living
      Plants.
AB  - Plants have a complex passive fluid transport system capable of internalizing
      small molecules from the environment, and this system offers an ideal route for
      augmenting plants with functional nanomaterials. Current plant augmentation
      techniques use pre-formed nanomaterials and permeabilizing agents or plant
      cuttings. A so far unexplored concept is the formation of the functional
      material, in situ, from precursors small enough to be passively internalized
      through the roots without harming the plants. Metal-organic frameworks are ideal
      for in situ synthesis as they are composed of metal ions coordinated with organic
      ligands and have recently been mineralized around single-celled organisms in mild
      aqueous conditions. Herein, the synthesis of two types of metal-organic
      frameworks, zinc(2-methylimidazole)2 and lanthanide2 (terephthalate)3 , are
      reported inside a variety of plants. In situ synchrotron experiments help
      elucidate the formation kinetics and crystal phases of the nano-biohybrid plants.
      Plants augmented with luminescent metal-organic frameworks are utilized for small
      molecule sensing, although other applications, such as pathogen sensing, proton
      conductive plants, improved CO2 capture, bacteria-free nitrogen fixation, drought
      and fungi-resistance, and enhanced photosynthesis and photocatalysis, are
      foreseeable. Overall, the generation of functional materials inside of fully
      intact plants could lead to more complex nano-biohybrid sensors and organisms
      augmented with superior performance characteristics.

PMID- 29168919
TI  - Comparison of Complexation-Induced pKa Shifts in the Ground and Excited States of
      Dyes as Well as Different Macrocyclic Hosts and Their Manifestation in Host
      Retarded Excited-Dye Deprotonation.
AB  - 1-Aminopyrene and 1-naphthylamine-5-sulfonic acid were converted to the
      putrescine (1,4-diaminobutane)-substituted derivatives (dyes 1 and 2). The
      diaminobutyl anchor serves as a common binding motive for cation-receptor
      macrocycles such as cucurbit[n]urils (n = 6-8) and p-sulfonatocalix[4]arene. When
      protonated, they are prone to undergo a rapid deprotonation in their excited
      state to result in fluorescence from the unprotonated form (Forster cycle). The
      deprotonation can be suppressed by complexation with cation-receptor macrocycles,
      which allows the fluorescence of the locally excited (protonated) state to be
      dramatically enhanced (factor 12 for dye 1 and 83 for dye 2). This host-retarded
      excited-dye deprotonation is a direct consequence of the previously established
      complexation-induced pKa shifts that dyes undergo upon binding to a macrocyclic
      host. The data set also allows a systematic comparison of complexation-induced
      pKa shifts in the ground and excited state of a dye. The trends are comparable,
      which suggests that structural factors, that is, the geometry of the host-guest
      complexes, determine the magnitude of the shifts. In regard to the magnitude of
      the absolute pKa shifts on the size of the macrocycles, we observe for dye 2 that
      the complexation-induced pKa shifts decrease as the portals become larger along
      the cucurbit[n]uril series.

PMID- 29168920
TI  - A case report of open craniofacial sutures, a novel feature of systemic
      sclerosis?
AB  - Scleroderma is an uncommon connective-tissue disease, its key feature being
      excessive collagen deposition resulting in fibrosis of the skin and internal
      organs. There are different types that can vary in severity from localized
      scleroderma to systemic sclerosis. Various clinical and radiographic findings can
      be attributed to the disease, which arise owing to the progressive nature of
      microvascular changes and collagen deposition. These include limited mouth
      opening, xerostomia, periodontal disease and cardiac and pulmonary disease.
      Whilst bone resorption has been reported, as far as we are aware, the literature
      has not described a case with failure of bony suture closure. Hence, we would
      like to describe what is probably a unique case of a patient with a 5-year
      history of systemic sclerosis, who was referred for management of increased
      mobility of her upper central incisors. Radiographic imaging (conventional and
      three-dimensional) confirmed increased bone resorption, partly owing to
      periodontal disease, but also owing to an open premaxillary suture. Similarly,
      other craniofacial sutures were diagnosed as being open, and, to our knowledge,
      this represents a yet undescribed finding in a patient suffering from
      scleroderma.

PMID- 29168921
TI  - Bauhinia forficata in the treatment of diabetes mellitus: a patent review.
AB  - INTRODUCTION: Diabetes Mellitus has been considered an epidemic by the World
      Health Organization, with a high risk of morbidity and mortality. The treatment
      of this pathology consists in glycemic control, which can be done by oral
      hypoglycemic agents, insulin therapy, dietary guidance, regular physical
      activity, and psychosocial support. In addition, other adjuvant treatments are
      employed, such as phytotherapic, and one of the most used plants is Bauhinia
      forficata. Areas covered: In the current review, patents using Bauhinia forficata
      for the Diabetes Mellitus treatment have been analyzed. There were 03 patents in
      WIPO, 01 in Espacenet, 01 in USPTO, and 02 in INPI. Expert opinion: Patents on
      the adjuvant treatment of Diabetes Mellitus by Bauhinia forficata are discussed.
      Although there are some phytotherapy products containing this medicinal plant
      which has hypoglycemic effect here is still a need for the development of more
      products based on natural resources, for the treatment of this pathology, without
      side effects and with other benefits, to assist in the glycemia control in
      diabetic patients, and to improve their quality of life.

PMID- 29168924
TI  - MENACTRIMS Congress 2018.

PMID- 29168922
TI  - Focused ultrasound: tumour ablation and its potential to enhance immunological
      therapy to cancer.
AB  - Various kinds of image-guided techniques have been successfully applied in the
      last years for the treatment of tumours, as alternative to surgical resection.
      High intensity focused ultrasound (HIFU) is a novel, totally non-invasive, image
      guided technique that allows for achieving tissue destruction with the
      application of focused ultrasound at high intensity. This technique has been
      successfully applied for the treatment of a large variety of diseases, including
      oncological and non-oncological diseases. One of the most fascinating aspects of
      image-guided ablations, and particularly of HIFU, is the reported possibility of
      determining a sort of stimulation of the immune system, with an unexpected
      "systemic" response to treatments designed to be "local". In the present article
      the mechanisms of action of HIFU are described, and the main clinical
      applications of this technique are reported, with a particular focus on the
      immune-stimulation process that might originate from tumour ablations.

PMID- 29168925
TI  - Enhanced degradation of 1-naphthol in landfill leachate using Arthrobacter sp.
AB  - Arthrobacter sp. named as JY5-1 isolated from contaminated soil of a coking plant
      can degrade 1-naphthol as the sole carbon source. Through identification of
      species, analysis of the optimal degradation condition and kinetic equation, the
      degradation characteristic of Arthrobacter sp. JY5-1 was obtained. Later, the
      acclimated strain was added into the bio-reactor to observe treatment performance
      of landfill leachate. The results showed that the optimal conditions for strain
      JY5-1 biodegradation in the study were pH 7.0 and 30oC. The bio-reactor operation
      experiment declared that Arthrobacter sp. JY5-1 had a strengthened effect on COD
      removal of landfill leachate. Moreover, the efficiency of COD removal could be
      high and stable when JY5-1 was accumulated as a biofilm together with active
      sludge. These results demonstrate that adding 1-naphthol-degrading strain JY5-1
      is a feasible technique for the enhanced treatment of sanitary landfill leachate,
      providing theoretical support for engineering utilization.

PMID- 29168923
TI  - Calpain-2 as a therapeutic target for acute neuronal injury.
AB  - INTRODUCTION: Calpains represent a family of neutral, calcium-dependent
      proteases, which modify the function of their target proteins by partial
      truncation. These proteases have been implicated in numerous cell functions,
      including cell division, proliferation, migration, and death. In the CNS, where
      calpain-1 and calpain-2 are the main calpain isoforms, their activation has been
      linked to synaptic plasticity as well as to neurodegeneration. This review will
      focus on the role of calpain-2 in acute neuronal injury and discuss the
      possibility of developing selective calpain-2 inhibitors for therapeutic
      purposes. Areas covered: This review covers the literature showing how calpain-2
      is implicated in neuronal death in a number of pathological conditions. The
      possibility of developing new selective calpain-2 inhibitors for treating these
      conditions is discussed. Expert opinion: As evidence accumulates that calpain-2
      activation participates in acute neuronal injury, there is interest in developing
      therapeutic approaches using selective calpain-2 inhibitors. Recent data indicate
      the potential use of such inhibitors in various pathologies associated with acute
      neuronal death. The possibility of extending the use of such inhibitors to more
      chronic forms of neurodegeneration is discussed.

PMID- 29168927
TI  - Synergism of CuS and tartaric acid in the reduction of Cr(VI) under an
      irradiation of simulated solar light.
AB  - The synergism of CuS and tartaric acid (TA) in the reduction of Cr(VI) with an
      irradiation of simulated solar light was investigated through observing the
      effects of solution pH, temperature, CuS loading and TA concentration on the
      removal efficiency of Cr(VI). Approximately 32% and 54% of the initial Cr(VI)
      (100 umol/L) were reduced within 180 min by TA and CuS with light, respectively.
      Under the same condition, however, almost a complete removal of the initial
      Cr(VI) was achieved within 130 min in the coexistence of CuS and TA. In the case,
      it is considered that Cr(VI) was rapidly reduced in two main pathways. One is
      that H2S produced from the dissolution of CuS in weak acidic solution directly
      reduced Cr(VI) to Cr(III). The other is that Cu(II) released from CuS reacted
      with TA to form complexes with photochemical activity, producing Cu(I) through
      ligand-to-metal electron transfer, and then the reduction of Cr(VI) was coupled
      with a conversion of Cu(I) to Cu(II). Thus, a cycle catalytic system was
      established for the reduction of Cr(VI). Moreover, it is observed that the
      reaction could be divided into two stages: the initial chemical reduction of
      Cr(VI) by H2S and the later photochemical reduction of Cr(VI) by Cu(II)-TA
      complexes.

PMID- 29168926
TI  - Three-dimensional imaging of soft and hard facial tissues in patients with
      craniofacial syndromes: a systematic review of methodological quality.
AB  - OBJECTIVES: To systematically review the methodological quality of three
      dimensional imaging studies of patients with craniofacial syndromes and to
      propose recommendations for future research. METHODS: PubMed, Embase and Cochrane
      databases as well as Grey literature were electronically searched. Inclusion
      criteria were patients with genetic syndromes with craniofacial manifestations
      and three-dimensional imaging of facial soft and/or hard tissues. Exclusion
      criteria consisted of non-syndromic conditions or conditions owing to
      environmental causes, injury or trauma, facial soft and hard tissues not included
      in the image analysis, case reports, reviews, opinion articles. No restrictions
      were made for patients' ethnicity nor age, publication language or publication
      date. Study quality was evaluated using the Methodological Index for Non
      Randomized Studies (MINORS). RESULTS: The search yielded 2228 citations of which
      116 were assessed in detail and 60 were eventually included in this review.
      Studies showed a large heterogeneity in study design, sample size and patient
      age. An increase was observed in the amount of studies with time, and the imaging
      method most often used was CT. The most studied craniofacial syndromes were
      Treacher Collins, Crouzon and Apert syndrome. The articles could be divided into
      three main groups: diagnostic studies (34/60, 57%), evaluation of surgical
      outcomes (21/60, 35%) and evaluation of imaging techniques (5/60, 8%). For
      comparative studies, the median MINORS score was 13 (12-15, 25-75th percentile),
      and for non-comparative studies, the median MINORS score was 8 (7-9, 25-75th
      percentile). CONCLUSIONS: The median MINORS scores were only 50 and 54% of the
      maximum scores and there was a lack of prospective, controlled trials with
      sufficiently large study groups. To improve the quality of future studies in this
      domain and given the low incidence of craniofacial syndromes, more prospective
      multicentre controlled trials should be set up.

PMID- 29168928
TI  - Regulation of Kv1.4 potassium channels by PKC and AMPK kinases.
AB  - Over the last years extensive kinase-mediated regulation of a number of voltage
      gated potassium (Kv) channels important in cardiac electrophysiology has been
      reported. This includes regulation of Kv1.5, Kv7.1 and Kv11.1 cell surface
      expression, where the kinase-mediated regulation appears to center around the
      ubiquitin ligase Nedd4-2. In the present study we examined whether Kv1.4,
      constituting the cardiac Ito,s current, is subject to similar regulation. In the
      epithelial Madin-Darby Canine Kidney (MDCK) cell line, which constitutes a highly
      reproducible model system for addressing membrane targeting, we find, by confocal
      microscopy, that Kv1.4 cell surface expression is downregulated by activation of
      protein kinase C (PKC) and AMP-activated protein kinase (AMPK). In contrast,
      manipulating the activities of phosphatidylinositol-4,5-bisphosphate 3-kinase
      (PI3K) and serum and glucocorticoid-regulated kinase 1 (SGK1) were without effect
      on channel localization. The PKC and AMPK-mediated downregulation of Kv1.4
      membrane surface localization was confirmed by two-electrode voltage clamp in
      Xenopus laevis oocytes, where pharmacological activation of PKC and AMPK reduced
      Kv1.4 current levels. We further demonstrate that unlike related Kv channels,
      Kv1.4 current levels in Xenopus laevis oocytes are not reduced by co-expression
      of Nedd4-2, or the related Nedd4-1 ubiquitin ligase. In conclusion, we
      demonstrate that the surface expression of Kv1.4 is downregulated by the two
      kinases AMPK and PKC, but is unaffected by PI3K-SGK1 signaling, as well as Nedd4
      1/Nedd4-2 activity. In the light of previous reports, our results demonstrate an
      impressive heterogeneity in the molecular pathways controlling the surface
      expression of highly related potassium channel subunits.

PMID- 29168930
TI  - Cyclodextrin encapsulation of daidzein and genistein by grinding: implication on
      the glycosaminoglycan accumulation in mucopolysaccharidosis type II and III
      fibroblasts.
AB  - This work aimed to investigate the potential effect of cyclodextrin encapsulation
      on intrinsic ability of daidzein (DAD) and genistein (GEN) to inhibit the
      glycosaminoglycan (GAG) synthesis in fibroblasts originating from patients with
      mucopolysaccharidosis (MPS), type II and III. DAD or GEN encapsulation with
      either 2-hydroxypropyl-beta-cyclodextrin or sulphobuthylether-beta-cyclodextrin
      were achieved by neat grinding and were characterised by thermal analysis, X-ray
      powder diffraction, scanning electron microscopy and solubility testing which
      confirmed the complexes formation with increased solubility with respect to
      starting compounds. Both isoflavones, as well as their co-ground cyclodextrin
      complexes reduced GAG levels in the fibroblasts of MPS II and MPS III patients
      from 54.8-77.5%, in a dose dependent manner, without any significant cytotoxic
      effect. Cyclodextrin encapsulation did not change the intrinsically high effect
      of both DAD and GEN on the GAG level reduction in the treated cells, thus could
      be considered as a part of combination therapies of MPS.

PMID- 29168929
TI  - Kinin B1 receptors as a therapeutic target for inflammation.
AB  - INTRODUCTION: Kinins are peptide mediators exerting their pro-inflammatory
      actions by the selective stimulation of two distinct G-protein coupled receptors,
      termed BKB1R and BKB2R. While BKB2R is constitutively expressed in a multitude of
      tissues, BKB1R is hardly expressed at baseline but highly inducible by
      inflammatory mediators. In particular, BKB1R was shown to be involved in the
      pathogenesis of numerous inflammatory diseases. Areas covered: This review
      intends to evaluate the therapeutic potential of substances interacting with the
      BKB1R. To this purpose we summarize the published literature on animal studies
      with antagonists and knockout mice for this receptor. Expert Opinion: In most
      cases the pharmacological inhibition of BKB1R or its genetic deletion was
      beneficial for the outcome of the disease in animal models. Therefore, several
      companies have developed BKB1R antagonists and tested them in phase I and II
      clinical trials. However, none of the developed BKB1R antagonists was further
      developed for clinical use. We discuss possible reasons for this failure of
      translation of preclinical findings on BKB1R antagonists into the clinic.

PMID- 29168931
TI  - Plasma concentrations of cytisine, a commercially available plant-based alkaloid,
      in healthy adult smokers taking recommended doses for smoking cessation.
AB  - 1. Cytisine is a plant alkaloid that is a partial agonist for the alpha4beta2 
      nAChRs and is used as an aid to smoking cessation. To date, there are no
      published data on cytisine concentrations in humans following multiple dosing.
      The aim of this study was to determine cytisine plasma concentrations after
      taking recommended doses for smoking cessation and to report on adverse effects.
      2. Subjects (n=10) were instructed to follow the 25-day standard dosing regimen
      of cytisine. Blood was collected at 0, 2, 4, 8 and 10 hours on day 1 then on
      subsequent visits (days 2, 3, 4, 6, 13, 14, 17, 18, 21, 22, 25 and 26) to measure
      plasma cytisine concentrations. Plasma concentrations were determined using a
      validated LC-MS method. 3. Accumulation of cytisine was observed with repeated
      dosing of cytisine on day 1. Mean +/- SEM plasma cytisine concentration measured
      at 10 hours was 50.8 +/- 4.7 ng/mL. Due to dose tapering, there was an overall
      decrease in plasma cytisine concentration over the whole treatment period. 4.
      Overall, cytisine was well-tolerated and adverse effects reported were minor,
      indicating that cytisine is safe at concentrations measured in this study. This
      study is registered in the Australia and New Zealand Clinical Trials Registry
      (ACTRN12613000002785).

PMID- 29168932
TI  - Two-step grafting of 2-hydroxyethyl methacrylate (HEMA) and 2
      (dimethylamino)ethyl methacrylate (DMAEMA) onto a polyethylene plate for
      enhancement of Cr(VI) ion adsorption.
AB  - Polyethylene (PE) plates grafted with a neutral monomer, 2-hydroxyethyl
      methacrylate (HEMA), and a cationic monomer, 2-(dimethylamino)ethyl methacrylate
      (DMAEMA), (PE-g-PHEMA)-g-PDMAEMA plates were prepared by the two-step
      photografting. The Cr(VI) ion adsorption behavior of the (PE-g-PHEMA)-g-PDMAEMA
      plates was investigated as a function of the amounts of grafted HEMA, amount of
      grafted DMAEMA, initial pH value, and temperature. The adsorption capacity of the
      DMAEMA-grafted PE (PE-g-PDMAEMA) and (PE-g-PHEMA)-g-PDMAEMA plates had the
      maximum value at the initial pH value of 3.0, independent of the temperature. The
      adsorption capacity of (PE-g-PHEMA)-g-PDMAEMA plates increased with the amount of
      grafted HEMA (GHEMA) in the first-step grafting. The increase in the water
      absorptivity of the grafted layers and thereby the increase in the degree of
      protonation of dimethylamino groups on grafted PDMAEMA chains were found to lead
      to the increase in the adsorption capacity. This adsorption capacity was higher
      than or comparable to those of other polymeric adsorbents for Cr(VI) ions. The
      Cr(VI) ion adsorption behavior on both PE-g-DMAEMA and (PE-g-PHEMA)-g-PDMAEMA
      plates obeyed the mechanism of the pseudo-second-order kinetic model and was well
      expressed by Langmuir isotherm. The high values of the Langmuir constant suggest
      that the adsorption of Cr(VI) ions occurs through an electrostatic interaction
      between protonated dimethylamino groups on grafted PDMAEMA chains and [Formula:
      see text]ions. Cr(VI) ions were successfully desorbed from PE-g-PDMAEMA and (PE-g
      PHEMA)-g-PDMAEMA plates in eluents such as NaCl, NaCl containing NaOH, NH4Cl,
      NH4Cl containing NaOH, and NaOH.

PMID- 29168933
TI  - Role of chemotherapy and targeted therapy in early-stage non-small cell lung
      cancer.
AB  - INTRODUCTION: Adjuvant platinum based chemotherapy is accepted as standard of
      care in stage II and III non-small cell lung cancer (NSCLC) patients and is often
      considered in patients with stage IB disease who have tumors >= 4 cm. The
      survival advantage is modest with approximately 5% at 5 years. Areas covered:
      This review article presents relevant data regarding chemotherapy use in the
      perioperative setting for early stage NSCLC. A literature search was performed
      utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in
      this setting including adjuvant and neoadjuvant use of chemotherapy as well as
      ongoing trials on targeted therapy and immunotherapy are also discussed. Expert
      commentary: With increasing utilization of screening computed tomography scans,
      it is possible that the percentage of early stage NSCLC patients will increase in
      the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients
      remain modest. There is a need to better define patients most likely to derive
      survival benefit from adjuvant therapy and spare patients who do not need
      adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant
      targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy
      drugs are ongoing and will define the role of these agents as adjuvant therapy.

PMID- 29168934
TI  - Challenging a dogma: five-year survival does not equal cure in all colorectal
      cancer patients.
AB  - BACKGROUND: The current study tried to evaluate the factors affecting 10- to 20-
      years' survival among long term survivors (>5 years) of colorectal cancer (CRC).
      METHODS: Surveillance, Epidemiology and End Results (SEER) database (1988-2008)
      was queried through SEER*Stat program.Univariate probability of overall and
      cancer-specific survival was determined and the difference between groups was
      examined. Multivariate analysis for factors affecting overall and cancer-specific
      survival was also conducted. RESULTS: Among node positive patients (Dukes C), 34%
      of the deaths beyond 5 years can be attributed to CRC; while among M1 patients,
      63% of the deaths beyond 5 years can be attributed to CRC. The following factors
      were predictors of better overall survival in multivariate analysis: younger age,
      white race (versus black race), female gender, Right colon location (versus
      rectal location), earlier stage and surgery (P <0.0001 for all parameters).
      Similarly, the following factors were predictors of better cancer-specific
      survival in multivariate analysis: younger age, white race (versus black race),
      female gender, Right colon location (versus left colon and rectal locations),
      earlier stage and surgery (P <0.0001 for all parameters). CONCLUSION: Among node
      positive long-term CRC survivors, more than one third of all deaths can be
      attributed to CRC.

PMID- 29168935
TI  - Epithelial plasticity and metastatic cascade.

PMID- 29168937
TI  - Managing the nutritional needs of palliative care patients.
AB  - The nutritional needs of patients receiving palliative care should be routinely
      assessed, taking into account disease trajectory and nutrition-related symptoms.
      The social and emotional aspects of eating and drinking should also be
      acknowledged; as should the distress that weight loss and anorexia engenders in
      patients and their families. Practical strategies to optimise nutritional intake
      are discussed. Open and sensitive communication of patients' needs and wishes is
      essential, especially when discussing complementary nutrition approaches. A
      holistic, multidisciplinary approach is key to meeting nutritional needs, and the
      goals of nutritional intervention should be regularly reviewed in the light of
      disease progression.

PMID- 29168936
TI  - Does CBCT alter the diagnostic thinking efficacy, management and prognosis of
      patients with suspected Stage 0 medication-related osteonecrosis of the jaws?
AB  - OBJECTIVES: To evaluate the impact of cone beam CT (CBCT) in the diagnostic
      thinking efficacy, management and prognosis of patients with suspected Stage 0
      medication-related osteonecrosis of the jaw (MRONJ). METHODS: For 15 patients
      with suspected Stage 0 MRONJ, clinical photographs, a panoramic radiograph and
      selected CBCT sections were identified. 13 oral surgeons reviewed the material
      and answered 10 questions in two different sessions. First session included
      clinical photographs and panoramic radiographs, while second session also
      included CBCT images. Questions (Qs) referred to dental disease and bone
      abnormalities (Qs 1, 2 and 3), differential diagnosis (Qs 4 and 5), patient
      management (Qs 6 and 7) and prognosis (Qs 8 and 9). Q 10 queried indication
      (first session) and usefulness (second session) of CBCT images. RESULTS: Qs 2, 3,
      5, 7 and 9 scores increased between sessions, with statistical differences for Qs
      2, 3, 5 and 7 (<0.05). Patients 2, 8 and 11 showed a significant increase in the
      average score of all Qs between sessions, while scores for patient 10 nearly
      reached statistical significance (p = 0.055). For Q 10, 57.4% of answers reported
      that CBCT was needed (first session) and was beneficial (second session).
      CONCLUSIONS: CBCT had a significant impact in differential diagnosis and
      management of patients with suspected Stage 0 MRONJ.

PMID- 29168938
TI  - High-dependency care: experiences of the psychosocial work environment.
AB  - AIM: to explore high-dependency care nurses' experiences of their psychosocial
      work environment. METHODS: four focus groups were conducted with 23 emergency and
      critical care hospital nurses in Brunei. All sessions were recorded, transcribed
      verbatim and analysed using inductive-approach thematic analysis. FINDINGS: three
      major themes were identified. 'Specialisation/specific skills' explained a
      fundamental requirement for the high-dependency care nurses to work effectively
      and efficiently in their workplace. 'Task completion' narrated the pressure they
      experienced to complete their tasks within time constraints exacerbated by a
      reduced number of staff. 'Acknowledgement' signified their need for fair and
      adequate reward for their hard work through career progression and promotion.
      CONCLUSION: this study facilitates the design of future interventions and
      policies that promote a healthy psychosocial work environment by ensuring nurses
      working in these areas have the required specialisation skills, there is a
      balance of workload and nurse-to-patient ratios, and they are offered fairness
      and equity in career progression and promotion.

PMID- 29168939
TI  - Implications for operationalising the new education standards for nursing.

PMID- 29168940
TI  - How peer facilitation can help nursing students develop their skills.
AB  - Nursing education is continuously evolving to meet Nursing and Midwifery Council
      (NMC) requirements for registered nurses. NMC standards state that all registered
      nurses are responsible for the student learning experience. However, newly
      qualified nurses can feel underprepared to support pre-registration student
      learning in the clinical area as the university setting does not facilitate
      formal peer support. This article will discuss the implementation of a peer
      facilitation scheme for pre-registration nursing students undertaking the BSc
      (Hons) and PGDip programmes in a higher education institution in London. The
      scheme trained second-year nursing students to be peer facilitators for first
      year clinical skills sessions. This article will also consider the benefits of
      the scheme for both first and second-year student nurses.

PMID- 29168941
TI  - Causes, assessment and management of fatigue in critically ill patients.
AB  - Fatigue is a common complaint among hospitalised patients and is one of the most
      prevalent and distressing symptoms reported by critically ill patients in the
      intensive care unit (ICU). Fatigue comes in many forms, is associated with a wide
      range of aetiologies, and is aggravated and intensified by a multitude of
      environmental and situational factors present in the intensive care environment.
      While assessing and evaluating fatigue is key to the effective management of this
      distressing symptom, reports have shown that fatigue assessment in the ICU is
      suboptimal and patients are often left suffering from its untoward consequences.
      Furthermore, the experience of fatigue that originates in the initial ICU
      admission often persists months to years after being discharged, and this has
      been shown to be associated with worse patient outcomes. Nurses are in an ideal
      position to identify, diagnose and evaluate patients who may be at risk of
      experiencing fatigue and put in place interventions as necessary. This article
      aims to discuss the incidence, causes, and clinical implications of fatigue among
      ICU patients and discuss ways in which nurses can effectively assess, diagnose,
      evaluate, manage and treat patient's fatigue within the ICU environment.

PMID- 29168942
TI  - Regulating the nursing associate profession.
AB  - Emeritus Professor Alan Glasper, University of Southampton, discusses the
      Government's consultation on changes to the Nursing and Midwifery Order 2001 and
      the legislation to regulate nursing associates.

PMID- 29168943
TI  - Flagging up flu vaccination.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, considers the campaign for
      staff flu vaccination, ways to promote uptake and the thorny issue of opt-out.

PMID- 29168944
TI  - Report card on the Care Quality Commission.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses the work and role of the Care Quality Commission through
      the lens of the National Audit Office report.

PMID- 29168945
TI  - Analysis of the experiences of nurses who return to nursing after cancer.
AB  - BACKGROUND: understanding the impact of role ambiguity (both professional and
      patient) can be a factor in deepening the understanding of the ongoing personal,
      professional and organisational requirements of nurses who are cancer survivors.
      PURPOSE: the aim of this qualitative study was to elucidate an in-depth
      description of nurses' experiences of surviving cancer. METHOD: an exploratory
      qualitative research design was used (n=8), with participants recruited between
      September 2014 and December 2016. DISCUSSION: data analysis led to the emergence
      of six themes: being practical about the diagnosis and treatment, empathy and
      compassion, a 'new normal' and the role of organisational support, medical
      knowledge and treatment experiences, coping in silence and denial, and being
      resilient. CONCLUSION: nurses as cancer survivors who return to work offer a
      richness of experience related to enhanced empathetic responses to patients in
      their care and have the potential to be great practice role-models for other
      staff.

PMID- 29168946
TI  - Using an electronic assessment system for nursing students on placements.
AB  - Electronic assessment is gaining popularity in clinically based elements of pre
      registration nurse education. In this study, the authors explored student nurse
      and mentor experiences during transition from a paper to an electronic system.
      Mixed research methods used included survey questionnaires and focus groups.
      Student nurses and their mentors (both n=5) discussed and rated their confidence
      and skills in information technology and their experience of an electronic
      assessment document before and after two successive clinical placements.
      Students' self-reported confidence increased after both placements; mentors'
      confidence fell after the first placement. Students reported the fewest needs for
      additional support, while mentors expressed anxieties about system navigation and
      time required. The main barrier was lack of access to computers connected to the
      internet in the practice environment. Nevertheless, students and mentors were
      receptive to the change. Training and support was seen as essential. Serious
      challenges in up-scaling this system for complete student cohorts lie in wait if
      computer availability is not addressed.

PMID- 29168947
TI  - Runner up 2017.

PMID- 29168948
TI  - Development and evaluation of an educational training package to promote health
      and wellbeing.
AB  - BACKGROUND: supporting the health and wellbeing of healthcare employees is a
      national priority in the UK. AIMS: to design, deliver and evaluate an educational
      package to promote health and wellbeing for nurses and midwives. METHODS: an
      online training package was developed and administered in two ways: online (HAWN
      online) or in a face-to-face workshop (HAWN-contact). A mixed methods evaluation
      was used to assess usability and acceptability of HAWN training. FINDINGS: 316
      nurses, midwives and students completed the online training package and 16
      participants attended the workshop. HAWN-online significantly increased knowledge
      in core areas of workplace health and wellbeing. Nurses and midwives valued
      online and face-to-face delivery but found there were barriers to attendance at
      workshops. Participants advocated that training in workplace health should be
      mandatory for all frontline staff. CONCLUSIONS: employers should take steps to
      promote staff wellbeing through HAWN training, and address barriers to accessing
      workplace health training or supportive services.

PMID- 29168949
TI  - What makes a difference?

PMID- 29168950
TI  - HIV: don't be complacent.

PMID- 29168952
TI  - Creating an appropriate environment for a person with dementia.

PMID- 29168951
TI  - An interesting conference, for some depressing reasons.

PMID- 29168953
TI  - From staff nurse to nurse consultant: Spiritual care part 8: Jehovah's Witnesses.
AB  - John Fowler, Educational Consultant, explores the role of clinically based nurses
      in caring for patients who are Jehovah's Witnesses.

PMID- 29168954
TI  - Social mobilization for safe transition from adolescence: a qualitative research
      in Iran.
AB  - Introduction Until now, the services provided to Iranian youth have been prepared
      based on authorities' perspectives and according to the resources and reports
      from other countries and international agencies. Using youth perspectives to
      provide health, however, helps in continuing the process of providing health
      services, and most young people will receive these services. Objective To explain
      perception of youth and key individuals to improve health programs for safe
      transition in Iran. Methodology This study is a qualitative research with a
      grounded theory approach. Data were collected using semi-structured in-depth
      interviews and group discussions. Participants were first selected by purposive
      sampling and then by theoretical sampling. Overall, 67 adolescents aged 14-18
      years, eight youths aged 19-24 years, 12 parents and important persons involved
      in providing health services joined the study. Young participants and their
      parents were selected from different training areas of Tehran and the key
      individuals were from the Ministry of Health and Medical Education and the
      Education Department. Collecting samples were continued to saturation. The
      Strauss and Corbin (2008) method was used for data analysis. Result In this
      study, the phenomenon of adolescents' confusion to manage puberty emerged. This
      process, with appropriate strategies, such as the mobilization of available
      resources in the community and comprehensive programming to provide health
      services by policymakers, could have provided youth empowerment as an impact to
      self-care. Conclusion Current services provided by health centers cannot
      guarantee the health of adolescents, but it does require proper planning and
      management in families, schools and societies.

PMID- 29168955
TI  - Adherence to a Mediterranean dietary pattern and overweight and obesity among
      female adolescents in Iran.
AB  - Background Given the high prevalence of overweight and obesity in Iran,
      identification of a healthy diet is essential. Objective This study aimed to
      assess the association between adherence to a Mediterranean diet and overweight
      and obesity in female adolescents. Methods Two hundred and eighty female
      adolescents from high schools in Tehran were recruited. General information,
      physical activity and food frequency questionnaires were completed. Adherence to
      the Mediterranean diet was evaluated using the Mediterranean Style Dietary
      Pattern Score (MSDPS). Results Under and over reporters of energy intake were
      excluded from the analysis (n = 37). Results indicated that prevalence of
      overweight and obesity was 13.3% and 12.5%, respectively. The mean of MSDPS was
      low in this population (15.99 +/- 5.64). The MSDPS was positively associated with
      mother's education level and energy intake (p < 0.05). No significant relation
      was observed between MSDPS and overweight and obesity among adolescents. However,
      there was a negative significant association between MSDPS and WHR just among
      students who had educated mothers [high: second median v. low: first median, odds
      ratio (OR) = 0.36, 95% confidence interval (CI) = 0.12-1.03]. Conclusion
      Adherence to a Mediterranean dietary pattern is low among adolescent females in
      Tehran, with no association with overweight and obesity.

PMID- 29168956
TI  - (Health-related) quality of life and psychosocial factors in adolescents with
      chronic disease: a systematic literature review.
AB  - Background Research on living with a chronic disease (CD) in adolescence is
      increasing. However, studies on the relevance of psychosocial factors are still
      needed. The present review, focuses on the impact of living with a CD in
      adolescence on on quality of life (QoL), health-related quality of life (HRQoL)
      and psychosocial factors. Methods A literature review of articles identified
      through PubMed, PsycINFO and PsycARTICLES (these last two ones comprise the Ebsco
      Host platform) and original peer-reviewed research papers, published between 2010
      and 2015, with no restrictions regarding the format/source of interventions,
      randomized controlled trials (RCTs) or types of comparisons were included.
      Results Eighteen papers met the inclusion criteria and contradictory results were
      found: the majority showed a significantly higher risk of impairment on QoL/HRQoL
      and psychosocial factors, whereas others reported a significantly lower risk of
      impairment (highlighting possible protective factors), or no significant
      differences. Heterogeneity in the assessment procedures and substantial
      difficulties in considering adolescence as a single and independent age group,
      were also noted. Conclusion The higher risk of impairment and the heterogeneity
      observed between cohorts, reinforce the need to work towards consensual
      procedures, which allow for more accurate comparisons among studies.
      Additionally, it conveys the challenge to find more effective interventions.
      Furthermore, it is highly suggested to routinely assess HRQoL/psychosocial
      factors within an individualized framework, to considerer adolescents as a
      single/independent group, to emphasize potential protective factors, and, to
      increase youth's participation in their own adaptation process and in health
      promotion in general. These are possible future directions that could enable
      multidisciplinary responses to improve HRQoL and psychosocial care in adolescents
      with a CD.

PMID- 29168957
TI  - The effects of introducing Tabata interval training and stability exercises to
      school children as a school-based intervention program.
AB  - Background Physical activities during leisure time as well as school hours have
      changed over the past few years, with adolescents being less physically active
      and adopting a sedentary lifestyle. Objective The overall objective of this mixed
      methods study was to evaluate the feasibility of introducing a 4-min Tabata
      interval training into a lower secondary school context. A further aim was to
      evaluate the possible effects on: coordination, balance, and strength. Methods
      The study was conducted as an intervention study with a mixed-method approach.
      Forty-three children, aged 7-9 years, participated in the intervention group.
      Additionally, 13 children were recruited as a control group. The intervention
      itself was delivered by the teachers and was performed for 4-min every day in a
      classroom setting. All participants performed physical tests before and after the
      intervention period to evaluate the Tabata training. After the completion of the
      6-week Tabata interval training, the four teachers were interviewed. Results The
      push-ups (p = 0.004), kneeling push-ups (p = 0.03), and standing long jump (p =
      0.01) improved in the intervention group after 6 weeks. No differences were
      observed between the genders. The teachers experienced that it worked well to
      integrate the Tabata interval training in the classroom setting. Conclusion After
      6 weeks, a school-based Tabata intervention program improved physical
      performance. The teachers saw no obstacles in including the Tabata intervention
      program in a classroom setting and pointed out several positive aspects such as
      an increased energy level and development in the children's movement patterns.

PMID- 29168958
TI  - Relationships between physical activity, food choices, gender and BMI in Southern
      Californian teenagers.
AB  - Given the increased prevalence of pediatric obesity and risk of developing
      chronic disease, there has been great interest in preventing these conditions
      during childhood by focusing on healthy lifestyle habits, including nutritious
      eating and physical activity (PA). The purpose of this study was to determine the
      relationship between PA, body mass index (BMI) and food choices in adolescent
      males and females. This cross-sectional study, using a survey questionnaire,
      evaluated 1212 Southern Californian adolescents' self-reported PA, BMI and food
      frequency. Results revealed that even though males are more active than females,
      they have higher BMI percentile values (p < 0.05). Females consumed salad,
      vegetables and fruit more frequently than males (p < 0.05), where males consumed
      hamburgers, pizza, red meat, processed meat, eggs, fish, fruit juice, soda and
      whole milk more frequently than females (p < 0.05). Overweight/obese teens
      consumed red meat, processed meat and cheese more frequently than healthy weight
      teens (p < 0.05), yet there was no difference in PA between healthy and
      overweight/obese teens. These results demonstrate that higher levels of PA may
      not counteract an unhealthy diet. Even though PA provides numerous metabolic and
      health benefits, this study suggests that healthy food choices may have a
      protective effect against overweight and obesity. Healthy food choices, along
      with PA, should be advocated to improve adolescent health by encouraging
      maintenance of a healthy weight into adulthood.

PMID- 29168959
TI  - Effect of a brief training program for primigravid adolescents on parenting self
      efficacy and mother-infant bonding in the southeast of Iran.
AB  - Background Annually, about 16 million adolescent girls give birth, accounting for
      11% of all births worldwide. Ninety-five percent of these births occur in low-
      and middle-income countries, and previous studies have addressed the need for
      parenting interventions in developing countries with limited health care
      resources to improve parenting behaviors. Objective To explore the effect of a
      brief training program for primigravid adolescents on parenting self-efficacy and
      mother-infant bonding. Subjects We enrolled 116 married pregnant adolescents.
      Methods This quasi-experimental study was conducted during August 22, 2016
      February 3, 2017. The intervention group received three sessions of training on
      neonatal care, while the control group received the routine care. We evaluated
      parenting self-efficacy using the Perceived Maternal Parenting Self-Efficacy (PMP
      S-E) questionnaire, the mother-infant bonding using the Postpartum Bonding
      Questionnaire (PBQ) and social support by means of the Multidimensional Scale of
      Perceived Social Support (MSPSS). The participants were followed up for 1 month.
      Results The mean ages of the intervention and the control groups were 16.37 +/-
      0.97 and 16.27 +/- 1.12 years, respectively. The intervention group obtained
      higher self-efficacy and bonding scores compared to the control group. The
      logistic regression model showed that the second (evoking behaviors) and the
      third (reading behavior or signaling) subscales of the PMP S-E, the route of
      delivery and women's educational levels could predict the mother-infant bonding
      scores. Conclusion Primigravid adolescents can benefit from brief interventions
      during pregnancy through improving their parenting self-efficacy and mother
      infant bonding.

PMID- 29168960
TI  - Using the Internet to access health-related information: results from a
      nationally representative sample of New Zealand secondary school students.
AB  - Objective To determine if secondary school students in New Zealand who report
      greater health concerns (e.g. significant depressive symptoms) are more likely to
      use the Internet to access health-related information. Methods A nationally
      representative health and wellbeing survey was undertaken in 2012 (n = 8500).
      Multiple regression models were used to examine the associations between
      students' use of the Internet to access health-related information and selected
      outcomes or indicators. Results Over 90% of students used the Internet on a daily
      basis, with 15.4% of students reporting that they had used the Internet to access
      health-related information. Students experiencing household poverty were more
      likely to report not using the Internet daily (17.4% compared to 4.2%). Odds
      ratios (ORs) for accessing the Internet for this sort of information were highest
      for students who reported self-harm [OR 2.7, 95% confidence interval (CI) 2.3
      3.3], disordered eating (OR 2.7, 95% CI 2.4-3.2), or a suicide attempt (OR 2.5,
      95% CI 1.9-3.3). Conclusion Our findings suggest that Internet-based health
      interventions may be a viable way to reach young people with high health needs,
      but consideration needs to be given to those with limited Internet access.

PMID- 29168961
TI  - Differences and similarities in medicine use, perceptions and sharing among
      adolescents in two different educational settings.
AB  - Background Evidence suggests that there are differences in medicine habits among
      adolescents with different sociodemographic backgrounds and that peers might also
      influence medicine use. More knowledge is needed regarding how these aspects
      together affect how different young people use medicines. Objective To explore
      the differences in medicine use, perceptions and sharing between adolescents at
      two different educational (and socio-demographic) settings and assess the
      influence of parents and peers. Subjects Fifty-nine students from a private high
      school (HS) and 34 students from a public vocational school (VS) in Denmark
      between the ages of 15 and 19 years old were subjects in this study. Methods A
      questionnaire was used that included background, medicine consumption,
      perceptions and social interaction. Descriptive analyses along with a Fishers
      test were used to determine differences and similarities between students'
      medicine patterns at the school settings. Results Of the 93 respondents, 74% used
      medicine within the past month, with females using more medicines. A significant
      difference was found with students at the VS using a higher number of medicines.
      Analgesics were the most frequently consumed medicine; however, reasons for using
      medicines appear to vary between the schools. Similarities between the schools
      were identified for perception of safety, sharing medicine and talking primarily
      with parents about medicine. Conclusion Fewer differences between students'
      medicine use at two educational settings than expected were identified, showing
      that aspects other than social background influence adolescents' use of medicine.
      A general tendency among young people believing that using medicines is a safe
      might explain these findings.

PMID- 29168962
TI  - Assessment of anxiety in adolescents involved in a study abroad program: a
      prospective study.
AB  - Objective The aim of the study was to measure the effects on levels of anxiety in
      healthy teenagers caused by a temporary change of country and school during a
      study abroad program. Methods In a prospective study we gathered the data from
      six anxiety level related tests on high school participants in a study abroad
      program (age 15-17, n = 364, M 172, F 192). These volunteer participants were
      divided into two separate groups: with self-reported elevated levels of anxiety
      (n = 111; YES-group) and with self-reported normal levels of anxiety (n = 253; NO
      group). Two control groups of schoolchildren drawn from two local schools were
      used for comparison (n = 100 each). Three tests were subjective, i.e. self-fill
      out tests. The next three tests were objective psychological or
      neurophysiological tests designed to estimate reflex control, concentration and a
      feeling for the passage of time. Results The initial mean anxiety level score
      among the 364 participants was 41.5 +/- 16.7 (min 16, max 80) on 5-110 scale. For
      the YES-group the score was 56.5 +/- 15.9, and for the NO-group the score was
      34.7 +/- 17.4 (p = 0.05). The retesting after they had been in the same place for
      7 weeks revealed that the mean anxiety level score of the participants decreased
      to 37.4 +/- 16.9 (min 15, max 72). For the YES-group the score significantly
      decreased to 39.3 +/- 15.5, and for the NO-group the score slightly elevated to
      36.7 +/- 16.4 producing similar results for both groups (p = 0.81). Conclusion A
      temporary change of country and school at first results in a rise in anxiety
      levels in about one third of participants. However, after an extended stay it
      falls to normal levels.

PMID- 29168963
TI  - A comparison of positive youth development against depression and suicidal
      ideation in youth from Hong Kong and the Netherlands.
AB  - Background This study tests the buffering effects of positive youth development
      (PYD) factors against depression and suicidal ideation across Hong Kong and Dutch
      students. Methods We collected data on depression, suicidal ideation, history of
      childhood maltreatment, and PYD from 565 Dutch and Hong Kong undergraduates. The
      three PYD factors, prosocial attributes, positive identity, and cognitive
      behavioral competence, were examined for their moderating role in the
      relationship among childhood maltreatment, depression, and suicidal ideation in
      path analysis. Results Direct protective effects are found for all PYD factors in
      both cultures, except for cognitive-behavioral competence in the Dutch sample. A
      buffering effect of the PYD factors is observed in the maltreatment-depression
      relationship in Dutch, but not in Hong Kong students. Only behavioral competence
      buffers against suicidal ideation in Dutch students, while other PYD factors show
      no buffering effect in both groups of participants. Conclusion The differences in
      relationships between two samples highlights the need to consider cultural
      differences.

PMID- 29168964
TI  - Using theory of planned behavior for prediction of delivery mode among pregnant
      women: a theory-based cross-sectional research.
AB  - Background Nowadays, in Iran cesarean rates have increased from the recommended
      level of the World Health Organization (WHO). Objectives The objective of the
      present study was to determine which theory of planned behavior (TPB) constructs
      predict intentions and delivery mode among pregnant women. Methods One hundred
      and four pregnant nulliparous women in their third trimesters of pregnancy
      referred to Semirom health care centers were investigated based on census
      reports. The data were collected by valid and reliable questionnaire based on the
      TPB constructs and analyzed by SPSS16. Results In examining predictors using
      linear regression analysis to choose normal vaginal delivery (NVD), all
      constructs of TPB, including attitude toward NVD (p < 0.0001), subjective norms
      (p < 0.05) and perceived behavioral control (p < 0.001) were significantly
      correlated. Finally, after telephone follow-up with the women who had delivered
      newborns on their delivery method, it was found that 71.15% had a NVD and 28.14%
      had a cesarean delivery. Conclusions Regarding the effect of attitude to NVD,
      subjective norms and perceived behavioral control in NVD intention and its
      crucial role in anticipating the final delivery method, it is recommended
      considering these constructs in designing educational interventions for safe
      delivery in the investigated area.

PMID- 29168965
TI  - Relationships between metabolic profile, hypertension and uric acid with
      cardiometabolic risk in adolescents with abdominal obesity: impact of
      geodemographic factors on the prevalence of abdominal obesity.
AB  - Background Association of hyperuricemia, dyslipidemia and high blood pressure
      (BP) among adolescents with high waist-to-height ratio (WHtR) remains not fully
      addressed and could represent a new way to diagnose adolescents early with
      cardiometabolic risk. Objective We aimed to determine abdominal obesity (AO)
      prevalence and investigate relations between AO, uric acid (UA), lipid profiles,
      BP and geographical patterns in adolescents. Subjects 577 and 204 Algerian
      students aged between 10 and 19 years were included in our epidemiological and
      biochemical studies, respectively. Methods Height, weight, waist circumference
      (Wc) and hip circumferences, body mass index (BMI) and BP were measured. Fasting
      blood sampling was performed to measure glycemia, lipid profile, uricemia,
      insulinemia and leptinemia. The WHtR >=0.50 was applied for the diagnosis of AO
      and geodemographics was evaluated. Results The prevalence of AO was 12.13% among
      all students, 19.17% and 16.39% among students living in urban and plain areas,
      respectively. The risk of AO may be reduced in rural and mountainous areas. Lipid
      parameters, UA, insulin and leptin serum concentrations were significantly
      increased in adolescents with WHtR >=0.50 compared to those with WHtR <0.50.
      Cardiometabolic risk was increased with WHtR >=0.50 and BMI >26. Means of BMI,
      Wc, BP, and lipid parameters were significantly increased in the fourth quartiles
      compared to the first quartile of UA. Conclusion Urban areas and plains represent
      factors contributing to AO and WHtR >=0.50 may be used as a cut-off point to
      define risks of high BP, lipid abnormalities and UA serum level in Algerian
      adolescents.

PMID- 29168966
TI  - Increased risk of sadness and suicidality among victims of bullying experiencing
      additional threats to physical safety.
AB  - Objective To examine, in a nationally-representative sample of high school
      students, to what extent one or more additional threats to physical safety
      exacerbates the risk of sadness and suicidality among victims of school and/or
      cyber-bullying. Methods National data from the 2015 Youth Risk Behavior Survey
      (YRBS) were analyzed for grades 9-12 (n = 15,624). Victimization groups were
      characterized by school-bullying and cyber-bullying, with and without additional
      threats to physical safety: fighting at school, being threatened/injured at
      school, and skipping school out of fear for one's safety. Outcomes included 2
      week sadness and suicidality. Outcomes for victimization groups were compared to
      non-victims using logistic regression adjusting for sex, grade and
      race/ethnicity. Results Overall, 20.2% of students were school-bullied, and 15.5%
      were cyber-bullied in the past year. Compared to non-victims, victims of school
      bullying and victims of cyber-bullying (VoCBs) who did not experience additional
      threats to physical safety were 2.76 and 3.83 times more likely to report 2-week
      sadness, and 3.39 and 3.27 times more likely to exhibit suicidality,
      respectively. Conversely, victims of bullying who experienced one or more
      additional threats to physical safety were successively more likely to report
      these adverse outcomes. Notably, victims of school-bullying and VoCBs with all
      three additional risk factors were 13.13 and 17.75 times more likely to exhibit
      suicidality, respectively. Conclusion Risk of depression symptoms and suicidality
      among victims of school-bullying and/or cyber-bullying is greatly increased among
      those who have experienced additional threats to physical safety: fighting at
      school, being threatened/injured at school and skipping school out of fear for
      their safety.

PMID- 29168967
TI  - Menstrual irregularity and use of oral contraceptives in female adolescent
      athletes in Swedish National Sports High Schools.
AB  - Objective Female adolescent athletes seem to use oral contraceptives (OCs) in the
      same proportion as the general population. In athletes not using OCs, menstrual
      irregularity (MI) is reported to be common but there are few studies of MI in
      adolescent athletes. The aim of the study was to survey menarche, menstrual
      irregularity and use of OCs in adolescent athletes in the National Sports High
      Schools in Sweden. A further aim was to study the associations between current
      sport injury and menstrual irregularity as well as use of OCs. Subjects Two
      hundred and ninety-eight female adolescent athletes at Swedish National Sports
      High Schools. Methods A web-based questionnaire containing questions related to
      menstrual status, contraception and current injury. Results One third (32.6%) of
      the athletes used OCs and of the remaining athletes 31.8% had MI. The group of
      athletes with MI had a significantly (p = 0.038; Cohen's d, 0.32) lower BMI and
      consisted of a significantly (p = 0.043) higher proportion of endurance athletes.
      OC users were less likely to participate in endurance sports compared to non-OC
      users (p = 0.024). Current injury was equally distributed in the OC and the non
      OC group but athletes with MI had fewer sports injuries compared to eumenorrheic
      women. Conclusion OCs are frequently used among athletes at Swedish National
      Sports High Schools. OC users were less likely to participate in endurance sports
      compared to non-OC users. MI was common and athletes with MI had lower BMI
      compared to eumenorrheic athletes. Sports injuries were not associated with use
      of OC and eumenorrheic athletes had a higher proportion of current injury.

PMID- 29168968
TI  - Cross-sectional comparison of age-related changes in the quadriceps femoris in
      Japanese basketball players.
AB  - Background This study examines age-related changes in the quadriceps femoris
      (QF), subdivided into the vastus medialis oblique (VMO), vastus medialis (VM),
      rectus femoris (RF), vastus intermedius (VI) and vastus lateralis (VL) in
      basketball players. Subjects Seventy male basketball players were divided into
      four groups according to age (12-13, 14-15, 16-17, and 18-20 years). Methods
      Ultrasonography was used to measure muscle architecture of the VMO, VM, RF, VI
      and VL. We created cubic approximate expressions and calculated inflexion points
      to evaluate peak growth age of each muscle head. Results Significant interactions
      were observed for all QF parts (p < 0.01-0.001). Muscle thickness (MT) in all QF
      parts was significantly lower in 12-13-year olds than in 18-20-year olds (p <
      0.01-0.001). Significant differences were recognised between 12-13 and 16-17-year
      olds in VM (p < 0.001), RF (p < 0.001) and VL (p = 0.007). MT was significantly
      lower in 14-15-year olds than in 16-17-year olds in the VM (p = 0.007) and RF (p
      = 0.026) and in 18-20 year olds in the VM (p < 0.001), RF (p = 0.036) and VI (p <
      0.001). Peak growth age was estimated for each QF part (VMO, 155.0 months; VM,
      187.8 months; RF, 212.2 months, VI, 188.9 months; VL, 181.1 months). Conclusion
      QF parts have different growth rates due to differing functions in each muscle
      head.

PMID- 29168969
TI  - Comparing health promotion behaviors of male and female high school students in
      Southeast of Iran.
AB  - Background Adolescence is one of the most challenging periods of human life. Many
      healthy or risky behaviors may be formed during this period and continue to the
      end of life. The aim of this study was to examine and compare the health
      promotion behaviors of male and female students in high schools. Methods In this
      descriptive-comparative study, 609 high school students were selected using multi
      stage random sampling method. Data were collected using demographic and health
      promoting lifestyle profile (HPLPII) questionnaires. Results The mean of health
      promotion behaviors was moderate in female (2.43 +/- 0.46) and male (2.61 +/-
      0.45) students. The highest and lowest means in the male students were
      respectively the dimensions of spiritual growth and health responsibility. Also,
      the highest and lowest means in the female students were dimensions of
      interpersonal relationships as well as physical activity and exercise. The status
      of male health promotion behaviors was significantly more favorable than that of
      the female (p = 0.001, t = -4.71). The male students had a better situation than
      female in terms of all the six dimensions of HPLPII, so there was a significant
      difference between them in the four dimensions of spiritual growth, stress
      management, physical activity and health responsibility. There was also a
      significant relationship between the history of physical and mental illness in
      the past year and the students' health promotion behaviors (p < 0.05). Conclusion
      The results indicated the importance of promoting self-care and educational
      interventions in the aspects such as physical activity and health responsibility
      of young people in order to improve the health of the community.

PMID- 29168970
TI  - Human adenovirus-36 seropositivity and obesity among Midwestern US adolescents.
AB  - Objective Human adenovirus-36 (Ad-36) infection has been implicated as a risk
      factor for obesity. This study aims to measure Ad-36 antibody prevalence among
      obese and healthy-weight Midwestern US adolescents. Methods Obese and healthy
      weight subjects 10-18 years of age attending an adolescent clinic in Missouri,
      USA, were tested for Ad-36 antibodies via ELISA assay. All subjects were measured
      for height and weight to determine body mass index (BMI). chi2 analysis was used
      to compare Ad-36 antibody prevalence between the two groups. Results Ad-36
      antibodies were tested on 41 obese and 37 control subjects. The subjects' mean
      age at the time of sample collection was 15.6 years (SD 2.0). Ad-36 antibody
      prevalence was 43.9% among the obese group and 21.6% among the control group (p =
      0.038). Discussion The findings show that statistically more obese Missouri
      adolescents test positive for Ad-36 antibodies than their healthy-weight peers,
      consistent with previous findings suggesting a correlation between Ad-36
      infection and obesity.

PMID- 29168971
TI  - Self perceived psychosocial impact of dental aesthetics among young adults: a
      cross sectional questionnaire study.
AB  - Background Oral health is not merely the absence of oral disease and dysfunction,
      but also influences the subject's social life and dento-facial self confidence.
      Objective To assess and correlate self perceived psychosocial impact of dental
      aesthetics among young adults based on gender. Subjects A convenience sample of
      Young adults of degree college in the age group of 18-23 years of Hyderabad city,
      India. Method Self perceived psychosocial impact of dental aesthetics was
      assessed using the psychosocial impact of dental aesthetics questionnaire
      (PIDAQ). The dental aesthetic index (DAI) was used to evaluate dental aesthetics
      among participants which includes 10 parameters of dento-facial anomalies related
      to both clinical and aesthetic aspects of the anterior teeth. Results The
      majority of the study population were 18 years of age (96; 31.4%) with a mean age
      of 19.2 +/- 1.1 years. When the mean total score and individual domain scores of
      PIDAQ was compared based on gender, females showed higher statistical mean (p <=
      0.05) for all except the psychology impact domain (p = 0.12). Based on DAI
      grading and gender, among both males [70 (32.9%)] and females [31 (33.3%)] the
      majority of them had a DAI score of <=25 (grade1; normal/minor dental
      malocclusion). A significant negative correlation was observed between DAI, with
      PIDAQ and its domains (p <= 0.05) except for the dental self confidence (p =
      0.72). Conclusion This study had examined the relationship between self-perceived
      psychosocial impact and dental aesthetics. So, early preventive or interceptive
      procedures should be carried out to prevent further psychosocial impacts on human
      life.

PMID- 29168972
TI  - Experience of violence amongst female medical and nursing students and their
      perception regarding violence against women in Delhi, India.
AB  - Background Health care providers are often the first point of contact for the
      victims of violence against women (VAW). Therefore, it is important to understand
      their perception about VAW. Objective To assess the proportion of female medical
      students who experienced violence, and elicit their perception regarding the
      same. Methods It was a cross-sectional study undertaken among 50 medical and 50
      nursing students of a medical college in Central Delhi. A self-administered,
      questionnaire was used for data collection. Results Of the total, 18% had
      experienced molestation while 77% had experienced eve-teasing during their
      lifetime. But, only 2% reported the incident to police. Perception regarding the
      victim's role and self-determination was favorable amongst the female students.
      However, only 39% knew some basic self-defense techniques. Conclusion The
      proportion of students who experienced eve-teasing in their lifetime was high.
      The study highlighted the need to make the female students more pro-active and
      competent in terms of tackling violence.

PMID- 29168973
TI  - Prevalence of obesity among youths in Mississippi: United States, 1999-2015.
AB  - Background The prevalence of obesity among youths has become a public health
      problem. The trend in the prevalence of obesity among high school students in
      Mississippi has not been examined in the last 17 years. Methods The data from the
      Mississippi High School Youth Risk Behavior Survey from 1999 to 2015 were used to
      determine the prevalence of obesity. The definition of obesity was based on age-
      and sex-specific body mass index (BMI) of more than 95th percentile, according to
      2000 Centers for Disease Control and Prevention (CDC) growth charts. The
      differences in the groups were examined using the univariate t-test statistical
      analysis at p < 0.05 and frequency distribution to determine the percentage
      differences. Results There was a decline in the prevalence of obesity from 1999
      to 2015 among Whites but no significant decrease among Blacks. The prevalence
      based on race in 2105 was 18.9%, which is higher than 14.4% in 1999 and remaining
      years. The rate of obesity based on race and sex was 27.7% among Blacks and 15.9%
      among White males in 2015. The Black females had prevalence of 20.6%, which is
      higher than their White counterpart (12.1%) in 2015 and previous years.
      Conclusion The prevalence of obesity among Blacks was higher when compared to
      White students. There was an increased prevalence of obesity in males over
      females. Students in 9th and 10th grade had a higher prevalence of obesity than
      those in 11th and 12th grade.

PMID- 29168974
TI  - HEEADSSS up: pediatric residents' confidence and practice in adolescent health
      care before and after mandatory adolescent medicine rotations in Thailand.
AB  - Background The field of adolescent medicine is an emerging area of specialization
      in Thailand. Adolescent medicine was made a mandatory rotation in general
      pediatric residency training programs for the class of 2013. Objective This study
      aims to explore the difference in pediatric residents' confidence and the
      frequency in providing aspects of care to adolescents. Subjects Participants
      included two groups of pediatric residents; the former curriculum group (FCG) in
      2012 and the mandatory curriculum group (MCG) in 2015. Methods Participants in
      this cross-sectional study answered a 41-item self-administered questionnaire and
      results were analyzed by descriptive statistics. Results There were 91
      participants, 50.05% were in the MCG. The FCG reported a higher percentage of
      feeling "more confident" on physical examination (p = 0.031, V = 0.23) and growth
      assessment (p = 0.040, V = 0.22). The MCG reported a higher percentage of "more
      frequently" carrying out the psychosocial assessment (p = 0.035, V = 0.22).
      Conclusion The FCG reported higher levels of confidence than the MCG in most of
      the items, while the MCG reported higher levels of frequency in providing care.
      The psychosocial (HEEADSSS) assessment, a key aspect of the adolescent clinical
      visit, was the item that the MCG reported doing more frequently than the FCG
      which remained significant when only the postgraduate year of training (PGY) 4s
      were compared.

PMID- 29168975
TI  - Treating malignant melanoma when a rare BRAF V600M mutation is present: case
      report and literature review.
AB  - Recent years have brought major advances in the treatment of malignant melanoma.
      One such an advance is the treatment with BRAF tyrosine-kinase inhibitors in
      metastatic malignant melanomas that harbor mutations in the BRAF gene. The trials
      that have been performed in this setting have demonstrated superior response
      rates and increased overall survival, however, they mostly included patients with
      melanomas carrying the more common V600E and V600K mutations, not being able to
      assess the benefit of these treatments in situations where more rare mutations of
      the BRAF gene are present. We present the evolution of a patient with malignant
      melanoma with a rare V600M mutation in the BRAF gene, that was eventually treated
      with vemurafenib. Also we present a brief review of the major phase III trials
      that showed benefit with tyrosine-kinase inhibitors in BRAF mutated melanoma,
      with respect to the BRAF mutations included.

PMID- 29168977
TI  - NLR and microalbuminuria: Are these markers significantly associated?

PMID- 29168976
TI  - Biological therapies in psoriasis - revisited.
AB  - Psoriasis is a chronic, immune mediated disorder affecting approximately 2% of
      the population. Even in our days, patients with psoriasis are confronted with
      stigmatization and social rejection. As a result, their quality of life is
      significantly impaired. Biological therapies have revolutionized the treatment of
      moderate to severe psoriasis. The aim of this paper is to look over the most
      important biological therapies available for the management of plaque-type
      psoriasis.

PMID- 29168978
TI  - Excitations in the quantum liquid 4He: A review.
AB  - Progress made in measuring and interpreting the elementary excitations of
      superfluid and normal liquid [Formula: see text] in the past 25 years is
      reviewed. The goal is to bring up to date the data, calculations and our
      understanding of the excitations since the books and reviews of the early 1990s.
      Only bulk liquid [Formula: see text] is considered. Reference to liquid [Formula:
      see text], mixtures, reduced dimensions (films and confined helium) is made where
      useful to enhance interpretation. The focus is on the excitations as measured by
      inelastic neutron scattering methods. The review covers the dynamical response of
      liquid [Formula: see text] from the collective excitations at low energy and long
      wavelength (i.e. phonon-roton modes) to the single particle excitations at high
      energy from which the atomic momentum distribution and Bose-Einstein condensate
      fraction are determined. A goal is to show the interplay of these excitations
      with other spectacular properties such as superfluidity and the test of
      fundamental calculations of quantum liquids that is possible. The role of Bose
      Einstein condensation in determining the nature of the [Formula: see text] mode
      and particularly it's temperature dependence is emphasized. The similarity of
      normal liquid [Formula: see text] with other quantum and classical liquids is
      discussed.

PMID- 29168979
TI  - Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in
      Surgically Resectable Pancreatic Neuroendocrine Tumors.
AB  - BACKGROUND The aim of this study was to evaluate the predictive and prognostic
      value of the preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to
      lymphocyte ratio (PLR) in pancreatic neuroendocrine tumor (PNET) patients
      undergoing potentially curative resection. MATERIAL AND METHODS A retrospective
      review of 172 patients with PNETs was conducted. Kaplan-Meier curves and
      multivariate Cox proportional models were used to calculate overall survival (OS)
      and disease-free survival (DFS). The predictive performance of the NLR was
      compared with other inflammation-based scores and conventional stratification
      systems using receiver operating characteristic (ROC) curve analysis. RESULTS
      Elevated NLR and PLR were both associated with advanced AJCC stage and high
      grade. In the univariate analysis, elevated NLR and PLR were both significantly
      associated with decreased OS and DFS. In the multivariate analysis, the
      preoperative NLR, but not the PLR, was an independent risk factor for OS
      (HR=4.471, 95% CI 1.531-13.054, p=0.006) and DFS (HR=2.531, 95% CI 1.202-5.329,
      p=0.015). The discriminatory capability of the NLR was superior to that of other
      inflammation-based scores in OS prediction. Furthermore, the predictive range was
      expanded by incorporating the NLR into the conventional stratification systems,
      including the AJCC stage and WHO classification systems. CONCLUSIONS As an
      independent prognostic factor, an elevated preoperative NLR is superior to the
      PLR with respect to predicting clinical outcomes in PNET patients undergoing
      potentially curative resection. The incorporation of the NLR into the existing
      conventional stratification systems improved the predictive accuracy.

PMID- 29168980
TI  - Inability to reduce morbidity of diarrhea by ORS: can we design a better therapy?
AB  - Diarrheal disease is a worldwide problem that still causes significant morbidity
      and mortality among children. Currently, oral rehydration solution (ORS) is the
      standard of care for acute diarrhea in pediatric patients. Although effective in
      reducing mortality, ORS does not alleviate diarrheal symptoms, thus reducing
      caregiver compliance and therapeutic efficacy. This article will briefly review
      the current problem of pediatric diarrhea and the shortcomings of current
      therapies; however, the focus of this review is to examine the intestinal calcium
      sensing receptor (CaSR). The author summarizes the evidence suggesting that
      targeting the CaSR will enable clinicians to address all four major
      pathophysiological mechanisms of diarrheal disease, and substantiates the need
      for future research regarding this therapy.

PMID- 29168981
TI  - High-resolution rapid neonatal whole-body composition using 3.0 Tesla chemical
      shift magnetic resonance imaging.
AB  - BackgroundTo evaluate a whole-body rapid imaging technique to calculate neonatal
      lean body mass and percentage adiposity using 3.0 Tesla chemical shift magnetic
      resonance imaging (MRI).MethodsA 2-Point Dixon MRI technique was used to
      calculate whole-body fat and water images in term (n=10) and preterm (n=15)
      infants.ResultsChemical shift images were obtained in 42 s. MRI calculated whole
      body mass correlated closely with measured body weight (R2=0.87; P<0.001). Scan
      rescan analysis demonstrated a 95% limit of agreement of 1.3% adiposity. Preterm
      infants were born at a median of 25.7 weeks' gestation with birth weight 840 g.
      At term-corrected age, former preterm infants were lighter than term-born
      controls, 2,519 vs. 3,094 g regressing out age and group as covariates (P=0.005).
      However, this was not because of reduced percentage adiposity 26% vs. 24%
      (P=0.28). At term-corrected age, former preterm infants had significantly reduced
      lean body mass compared with that of term-born controls 1,935 vs. 2,416 g
      (P=0.002).ConclusionRapid whole-body imaging for assessment of lean body mass and
      adiposity in term and preterm infants is feasible, accurate, and repeatable.
      Deficits in whole-body mass in former preterm infants at term-corrected age are
      due to reductions in lean body mass not due to differences in adiposity.

PMID- 29168983
TI  - Reverse cascade screening for familial hypercholesterolemia in high-risk Chinese
      families.
AB  - BACKGROUND: Reverse cascade screening is not commonly employed to detect new
      cases of familial hypercholesterolemia (FH). We aimed to assess the outcome of
      this screening strategy in families in which the probands were children with
      severe FH. HYPOTHESIS: Reverse cascade screening is an effective method to detect
      new patients with FH. METHODS: Reverse cascade screening was undertaken starting
      from 47 index children with severe hypercholesterolemia; 39 were
      homozygous/compound heterozygous FH and 8 were heterozygous FH. Available
      parents, siblings, and second-degree relatives were contacted and screened.
      RESULTS: From the 39 cases of homozygous/compound heterozygous FH, 80 first
      degree family members were available for screening; 70 were parents and 10 were
      siblings. All first-degree relatives screened were genetically diagnosed with FH.
      None of the parents had been treated with statins at the time of diagnosis, and
      10 (12.7%) had premature coronary artery disease. Additionally, 46 second-degree
      relatives were screened, of which 41 (89%) were diagnosed with FH. From the 8
      heterozygous FH children, 17 first- and second-degree relatives were screened and
      12 new cases of FH were also diagnosed. Hence, the overall diagnostic yield of
      screening was 2.8 new cases of FH per index case. CONCLUSIONS: Reverse cascade
      screening is a highly effective method for diagnosing new cases of FH in parents,
      siblings, and second-degree relatives of index children with severe FH.

PMID- 29168984
TI  - Transcatheter vs surgical aortic-valve replacement in low- to intermediate
      surgical-risk candidates: A meta-analysis and systematic review.
AB  - The American and European expert documents recommend transcatheter aortic valve
      replacement (TAVR) for inoperable or high-surgical-risk patients with severe
      aortic stenosis. In comparison, efficacy of TAVR is relatively less studied in
      low- to intermediate-surgical-risk patients. We sought to discover whether TAVR
      can be as effective as surgical aortic valve replacement (SAVR) in low- to
      intermediate-surgical-risk candidates. Four randomized clinical trials (RCTs) and
      8 prospective matched studies were selected using PubMed/MEDLINE, Embase, and
      Cochrane Library (inception: March 2017). Results were reported as random-effects
      odds ratio (OR) with 95% confidence interval (CI). Among 9851 patients, analyses
      of RCTs showed that all-cause mortality was comparable between TAVR and SAVR
      (short term, OR: 1.19, 95% CI: 0.86-1.64, P = 0.30; mid-term, OR: 0.97, 95% CI:
      0.75-1.26, P = 0.84; and long term, OR: 0.97, 95% CI: 0.81-1.16, P = 0.76). The
      analysis restricted to matched studies showed similar outcomes. In the analysis
      stratified by study design, no significant differences were noted in the RCTs for
      stroke, whereas TAVR was better than SAVR in matched studies at short term only
      (OR: 0.46, 95% CI: 0.33-0.65, P < 0.001). TAVR is associated with reduced risk of
      acute kidney injury and new-onset atrial fibrillation (P < 0.05). However,
      increased incidence of permanent pacemaker implantation and paravalvular leaks
      was observed with TAVR. TAVR can provide similar mortality outcome compared with
      SAVR in low- to intermediate-surgical-risk patients with critical aortic
      stenosis. However, both procedures are associated with their own array of adverse
      events.

PMID- 29168985
TI  - Association between diet quality and measures of body adiposity using the Rate
      Your Plate survey in patients presenting for coronary angiography.
AB  - BACKGROUND: Diet is a modifiable risk factor for cardiovascular disease; however,
      dietary patterns are historically difficult to capture in the clinical setting.
      Healthcare providers need assessment tools that can quickly summarize dietary
      patterns. Research should evaluate the effectiveness of these tools, such as Rate
      Your Plate (RYP), in the clinical setting. HYPOTHESIS: RYP diet quality scores
      are associated with measures of body adiposity in patients referred for coronary
      angiography. METHODS: Patients without a history of coronary revascularization (n
      = 400) were prospectively approached at a tertiary medical center in New York
      City prior to coronary angiography. Height, weight, and waist circumference (WC)
      were measured; body mass index (BMI) and waist-to-height ratio (WHtR) were
      calculated. Participants completed a 24-question RYP diet survey. An overall
      score was computed, and participants were divided into high (>=58) and low (<=57)
      diet quality groups. RESULTS: Participants in the high diet quality group (n =
      98) had significantly lower measures of body adiposity than did those in the low
      diet quality group (n = 302): BMI (P < 0.001), WC (P = 0.001), WHtR (P = 0.001).
      There were small but significant inverse correlations between diet score and BMI,
      WC, and WHtR (P < 0.001). These associations remained significant after
      adjustment for demographics, tobacco use, and socioeconomic factors. CONCLUSIONS:
      Higher diet quality scores are associated with lower measures of body adiposity.
      RYP is a potential instrument to capture diet quality in a high-volume clinical
      setting. Further research should evaluate the utility of RYP in cardiovascular
      risk-factor control.

PMID- 29168986
TI  - Skin aging parameters: A window to heart block.
AB  - BACKGROUND: Skin acts as a mirror to the internal state of the body. HYPOTHESIS:
      We tried to find the relation between skin aging parameters and the incidence of
      degenerative AV block. METHODS: This study included 97 patients divided into 2
      groups; group D comprised 49 patients with advanced-degree AV block, and group C
      comprised the 48 matched control group. All were subjected to full history
      taking, thorough clinical examination, calculation of intrinsic skin aging score,
      and resting 12-lead surface electrocardiography (ECG). ECG for all patients
      assessed left ventricular end-systolic diameter, left ventricular end-diastolic
      diameter, ejection fraction, left atrium (LA) diameter, aortic root diameter,
      mitral annular calcification, aortic sclerosis. Coronary angiography was also
      performed when indicated for patients in group D. RESULTS: Patients in group D
      had a higher percentages of uneven pigmentation, fine skin wrinkles, lax
      appearance, seborrheic keratosis, total score > 7 (38 [77.55%] vs 10 [20.83%]),
      mitral annular calcification score of 33 (67.34%) vs 5 (10.41%), aortic sclerosis
      score of 21 (42.85%) vs 4 (8.33%), and mean LA diameter of 39.98 +/- 5.52 vs
      36.21 +/- 3 mm (P < 0.001). Total score > 6 is the best cutoff value to predict
      advanced-degree heart block with 89.79% sensitivity and 64.58% specificity.
      Seborrheic keratosis was the strongest independent predictor. CONCLUSIONS: Any
      population with a total intrinsic skin aging score of >6 is at high risk for
      developing advanced-degree AV block and should undergo periodic ECG follow-up for
      early detection of any conduction disturbance in the early asymptomatic stages to
      minimize sudden cardiac death.

PMID- 29168982
TI  - N-terminomics reveals control of Arabidopsis seed storage proteins and proteases
      by the Arg/N-end rule pathway.
AB  - The N-end rule pathway of targeted protein degradation is an important regulator
      of diverse processes in plants but detailed knowledge regarding its influence on
      the proteome is lacking. To investigate the impact of the Arg/N-end rule pathway
      on the proteome of etiolated seedlings, we used terminal amine isotopic labelling
      of substrates with tandem mass tags (TMT-TAILS) for relative quantification of N
      terminal peptides in prt6, an Arabidopsis thaliana N-end rule mutant lacking the
      E3 ligase PROTEOLYSIS6 (PRT6). TMT-TAILS identified over 4000 unique N-terminal
      peptides representing c. 2000 protein groups. Forty-five protein groups exhibited
      significantly increased N-terminal peptide abundance in prt6 seedlings, including
      cruciferins, major seed storage proteins, which were regulated by Group VII
      Ethylene Response Factor (ERFVII) transcription factors, known substrates of
      PRT6. Mobilisation of endosperm alpha-cruciferin was delayed in prt6 seedlings. N
      termini of several proteases were downregulated in prt6, including RD21A. RD21A
      transcript, protein and activity levels were downregulated in a largely ERFVII
      dependent manner. By contrast, cathepsin B3 protein and activity were upregulated
      by ERFVIIs independent of transcript. We propose that the PRT6 branch of the
      pathway regulates protease activities in a complex manner and optimises storage
      reserve mobilisation in the transition from seed to seedling via control of
      ERFVII action.

PMID- 29168987
TI  - Independent predictors of effective blood pressure control in patients with
      hypertension on drug treatment in Brazil.
AB  - Population assessment of effective blood pressure (BP) control is fundamental for
      reducing the global burden of hypertension, especially in low- and middle-income
      countries. The authors evaluated the effectiveness of BP control and determined
      independent predictors associated with effective control among patients with
      hypertension on drug treatment in a large cross-sectional study performed in two
      metropolitan areas in Brazil's southeast region. A total of 43 647 patients
      taking antihypertensive treatment were identified. Less than half of the patients
      (40.9%) had controlled BP (systolic BP <140 mm Hg and diastolic BP <90 mm Hg).
      Independent predictors of BP control were age, eating fruit daily, physical
      activity, previous cardiovascular disease, male sex, diabetes mellitus,
      ethnicity, and obesity. Simple variables associated with BP control may be
      utilized for knowledge translation strategies aiming to reduce the burden of
      hypertension.

PMID- 29168988
TI  - Characterizing Risk for Cumulative Risk Assessments.
AB  - In assessing environmental health risks, the risk characterization step
      synthesizes information gathered in evaluating exposures to stressors together
      with dose-response relationships, characteristics of the exposed population, and
      external environmental conditions. This article summarizes key steps of a
      cumulative risk assessment (CRA) followed by a discussion of considerations for
      characterizing cumulative risks. Cumulative risk characterizations differ
      considerably from single chemical- or single source-based risk characterization.
      CRAs typically focus on a specific population instead of a pollutant or pollutant
      source and should include an evaluation of all relevant sources contributing to
      the exposures in the population and other factors that influence dose-response
      relationships. Second, CRAs may include influential environmental and population
      specific conditions, involving multiple chemical and nonchemical stressors.
      Third, a CRA could examine multiple health effects, reflecting joint toxicity and
      the potential for toxicological interactions. Fourth, the complexities often
      necessitate simplifying methods, including judgment-based and semi-quantitative
      indices that collapse disparate data into numerical scores. Fifth, because of the
      higher dimensionality and potentially large number of interactions, information
      needed to quantify risk is typically incomplete, necessitating an uncertainty
      analysis. Three approaches that could be used for characterizing risks in a CRA
      are presented: the multiroute hazard index, stressor grouping by exposure and
      toxicity, and indices for screening multiple factors and conditions. Other key
      roles of the risk characterization in CRAs are also described, mainly the
      translational aspect of including a characterization summary for lay readers (in
      addition to the technical analysis), and placing the results in the context of
      the likely risk-based decisions.

PMID- 29168989
TI  - Should I Stay or Should I Go Now? Or Should I Wait and See? Influences on
      Wildfire Evacuation Decisions.
AB  - As climate change has contributed to longer fire seasons and populations living
      in fire-prone ecosystems increase, wildfires have begun to affect a growing
      number of people. As a result, interest in understanding the wildfire evacuation
      decision process has increased. Of particular interest is understanding why some
      people leave early, some choose to stay and defend their homes, and others wait
      to assess conditions before making a final decision. Individuals who tend to wait
      and see are of particular concern given the dangers of late evacuation. To
      understand what factors might influence different decisions, we surveyed
      homeowners in three areas in the United States that recently experienced a
      wildfire. The Protective Action Decision Model was used to identify a suite of
      factors previously identified as potentially relevant to evacuation decisions.
      Our results indicate that different beliefs about the efficacy of a particular
      response or action (evacuating or staying to defend), differences in risk
      attitudes, and emphasis on different cues to act (e.g., official warnings,
      environmental cues) are key factors underlying different responses. Further,
      latent class analysis indicates there are two general classes of individuals:
      those inclined to evacuate and those inclined to stay, and that a substantial
      portion of each class falls into the wait and see category.

PMID- 29168990
TI  - Model-Based Meta-Analysis for Multiple Myeloma: A Quantitative Drug-Independent
      Framework for Efficient Decisions in Oncology Drug Development.
AB  - The failure rate for phase III trials in oncology is high; quantitative
      predictive approaches are needed. We developed a model-based meta-analysis (MBMA)
      framework to predict progression-free survival (PFS) from overall response rates
      (ORR) in relapsed/refractory multiple myeloma (RRMM), using data from seven phase
      III trials. A Bayesian analysis was used to predict the probability of technical
      success (PTS) for achieving desired phase III PFS targets based on phase II ORR
      data. The model demonstrated a strongly correlated (R2 = 0.84) linear
      relationship between ORR and median PFS. As a representative application of the
      framework, MBMA predicted that an ORR of ~66% would be needed in a phase II study
      of 50 patients to achieve a target median PFS of 13.5 months in a phase III
      study. This model can be used to help estimate PTS to achieve gold-standard
      targets in a target product profile, thereby enabling objectively informed
      decision-making.

PMID- 29168991
TI  - An Assessment of the Cox Proportional Hazards Regression Model for Epidemiologic
      Studies.
AB  - The basic assumptions of the Cox proportional hazards regression model are rarely
      questioned. This study addresses whether hazard ratio, i.e., relative risk (RR),
      estimates using the Cox model are biased when these assumptions are violated. We
      investigated also the dependence of RR estimates on temporal exposure
      characteristics, and how inadequate control for a strong, time-dependent
      confounder affects RRs for a modest, correlated risk factor. In a realistic
      cohort of 500,000 adults constructed using the National Cancer Institute Smoking
      History Generator, we used the Cox model with increasing control of smoking to
      examine the impact on RRs for smoking and a correlated covariate X. The smoking
      associated RR was strongly modified by age. Pack-years of smoking did not
      sufficiently control for its effects; simultaneous control for effect
      modification by age and time-dependent cumulative exposure, exposure duration,
      and time since cessation improved model fit. Even then, residual confounding was
      evident in RR estimates for covariate X, for which spurious RRs ranged from 0.980
      to 1.017 per unit increase. Use of the Cox model to control for a time-dependent
      strong risk factor yields unreliable RR estimates unless detailed, time-varying
      information is incorporated in analyses. Notwithstanding, residual confounding
      may bias estimated RRs for a modest risk factor.

PMID- 29168993
TI  - Brain Injury in Term Infants: The 'Each Baby Counts' Programme.

PMID- 29168992
TI  - Why it is nonsensical to use retrospective power analyses to conduct a postmortem
      on your study.

PMID- 29168994
TI  - Adenotonsillectomy for obstructive sleep apnoea in children with Down Syndrome -
      No magic bullet.

PMID- 29168995
TI  - Hospital Resource Utilisation by Patients with Community-Acquired Pneumonia.
AB  - Little data is available on the resource utilisation of patients admitted with
      Community-Acquired Pneumonia (CAP) in Ireland. A retrospective review of 50
      randomly-selected patients admitted to Beaumont Hospital with CAP was undertaken.
      The mean length of stay of patients with CAP was 12 days (+/- 16 days). All
      patients were emergency admissions, all had a chest x-ray, a C-reactive protein
      blood test, and occupied a public bed at some point during admission. Common
      antimicrobial therapies were intravenous (IV) amoxicillin/clavulanic acid and
      oral clarithromycin; 60% received physiotherapy. The estimated mean cost of CAP
      per patient was ?14,802.17. Costs arising from admission to hospital with CAP are
      substantial, but efforts can be undertaken to ensure that resources are used
      efficiently to improve patient care such as discharge planning and fewer in
      hospital ward transfers.

PMID- 29168996
TI  - Cancer Incidence and Mortality due to Excess Body Weight in Ireland: An Analysis
      of 10-year data.
AB  - Excess body weight (EBW) increases the risk of specific cancers. The prevalence
      of EBW has risen significantly in Ireland over recent decades. To highlight the
      impact on cancer, and to inform future policies, we calculated the proportion of
      cancers in Ireland that were attributable to EBW using the Population
      Attributable Fraction (PAF). This fraction was then applied to Irish incidence
      and mortality data for specific cancers from 2003-2012 to estimate the number of
      new cancers and cancer deaths attributable to EBW. We found that each year in
      Ireland, approximately 800 new cancers and 300 cancer deaths are attributable to
      EBW. The greatest attributable risk of cancer was seen for the upper digestive
      tract and endometrium, whilst breast and colorectal have the greatest numbers of
      attributable cancers. EBW is a major cause of cancer, responsible for 4.5% of all
      cancers in Ireland. Public awareness of this significant preventable risk must
      improve.

PMID- 29168997
TI  - A Retrospective Audit of In-Hospital 30-day Mortality from Acute Myocardial
      Infarction in Connolly Hospital Blanchardstown.
AB  - In 2015, The Department of Health published the first annual report of the
      "National Healthcare Quality Reporting System." Connolly Hospital was reported to
      a mortality rate within 30 days post-Acute Myocardial Infarction (AMI) of 9.87
      per 100 cases which was statistically significantly higher than the national
      rate. We carried out a retrospective audit of patients who were HIPE-coded as
      having died within 30 days of AMI from 2011-2013 and identified 42 patients. On
      review, only 23 patients (54.8%) were confirmed as having had an AMI. We
      identified 12 patients who had AMI included on death certificate without any
      evidence for same. If the 22 patients incorrectly coded were excluded, the
      mortality rate within 30 days post-AMI in CHB would fall to 4.14 deaths per 100
      cases, well below the national average. Inaccuracies of data collection can lead
      to erroneous conclusions when examining healthcare data.

PMID- 29168998
TI  - Three year Experience of Non-Melanoma Skin Cancer in a General Practice.
AB  - We report 85 lesions of non-melanoma skin cancer in 58 patients, representing 9%
      of the minor surgical workload of a single general practitioner. Cases were
      studied in order to describe pathology, management and outcomes. Eighteen percent
      of lesions were referred, mainly because of central facial site and larger size.
      Of the lesions treated in the surgery, all but four were treated surgically.
      Quantitative margins of lateral and deep excision were reported for 50% and 30%
      of specimens respectively. Lateral histological margins of clearance were
      narrower for head and neck lesions. Incomplete excision occurred in 4%. There was
      one recurrent lesion after two years of follow-up. A majority of non-melanoma
      skin cancers at this clinic were managed safely without referral to secondary
      care. Quantitative reporting of tumour free margins for skin cancer is lacking.

PMID- 29168999
TI  - Investigating the Perceived Benefits, Barriers and Beliefs towards Physical
      Activity in Pregnancy among Women with Gestational Diabetes Mellitus.
AB  - Gestational Diabetes Mellitus (GDM) is a growing concern and poses serious health
      risks to both mother and child1. The current study explores the psychological
      determinants of exercise behaviour in a sample of pregnant women with GDM. A
      cross-sectional survey design was employed to examine exercise behaviour, illness
      perceptions, perceived barriers and benefits, exercise beliefs, and exercise self
      efficacy using validated questionnaires. A sample of 46 pregnant women was
      recruited from University College Hospital Galway, Letterkenny General Hospital,
      Cork University Hospital and Mayo General Hospital in Castlebar. Participant's
      varied; age (22-44 years), body mass index (19-41). High mean scores for Personal
      Control (24.5) and Treatment Control (30.2) subscales indicated strongly held
      positive beliefs in relation to controllability of the illness. Total MET
      min/week score was not related to any psychological variables. Analysis of the
      IPQ-R data revealed 'diet' (n=37, 80.4%) as the most referred to cause of
      diabetes. Exercise belief data identified "managing weight gain" (n= 21, 45.7%),
      and "losing baby weight" (n= 31, 67.4%) as the most frequent beliefs for engaging
      in physical activity during pregnancy and post pregnancy. Further research on the
      psychological determinants of physical activity behaviour among this population
      group is needed in order to create successful intervention strategies.

PMID- 29169000
TI  - Hidradenitis Suppurativa and Crohn's Disease: A Case Series.
AB  - Hidradenitis Suppurativa (HS) is characterized by chronic recurrent abscesses,
      nodules and draining sinus tracts with scar formation. Cutaneous Crohn's Disease
      (CD) may also present similarly. We wished to identify and describe an Irish
      cohort with combined HS and CD, with a view to a better recognition of clinical
      manifestations and understanding of the pathophysiology underlying these two
      overlapping conditions. Cases were identified using the HIPE Code at Tallaght
      Hospital from 1990-2014 and retrospective review was performed. Seven patients
      with both HS and CD were identified, 5(71%) female. The median age of diagnosis
      with both conditions was 37 years. In all cases, CD had preceded the diagnosis of
      HS. All patients smoked. Six had an increased BMI and 43% had additional
      autoimmune conditions. All patients required treatment with a TNF-alpha inhibitor
      for HS with 5 of 6 subjects having reduced frequency of flare ups and clinically
      less active HS on follow up.

PMID- 29169001
TI  - Ivacaftor for cystic fibrosis: An evaluation of real world utilisation and
      expenditure in the Irish Healthcare Setting.
AB  - In Ireland, Ivacaftor is reimbursed, on the High-Tech Drug Scheme, for the
      treatment of cystic fibrosis in patients age 6 years and older who have the G551D
      mutation. The aim of this study was to analyse the utilisation and expenditure of
      Ivacaftor on this scheme in the 12 month period post-reimbursement. All patients
      who had received Ivacaftor (regardless of General Medical Services Scheme
      eligibility/ineligibility) were included. A total of 140 individuals (male=74;
      53%) received Ivacaftor over the defined 12 month study period (from January 2015
      to December 2015 inclusive). The cohort ranged in age from 6 years to 61 years.
      The mean age was 22 years; a positive skew in age distribution indicated that a
      greater number of the cohort were in the younger age groups. No statistically
      significant difference was detected in the mean ages of the male and female
      subgroups. Drug acquisition expenditure by the Health Services Executive on
      Ivacaftor over the 12 month study period was ?29.81 million.

PMID- 29169002
TI  - Skin Cancer Awareness Amongst Irish Golfers.
AB  - Aim The aim of this study was to assess skin cancer awareness and identify the UV
      protective measures used by golfers within the Munster region of Ireland. Methods
      Subjects were recruited from throughout the Munster region at a regional
      competition, and at three other local golf clubs and "pro" shops. Participants
      filled out a short anonymous validated questionnaire when collecting their score
      cards7. Results One hundred and sixty-three golfers completed the questionnaire
      with a mean age of 65.6 years. 137 (84%) were male and 26 (16%) were female. We
      noted a high incidence of both non-melanoma and melanoma skin cancer in our
      subjects. Sixteen (9.8%) had a previous history of skin cancer, with 8 melanomas
      and 8 non-melanoma skin cancers. A high percentage, 85%, of the golfers surveyed
      were compliant with SPF use. However many were using too low a SPF, 63 (44%) were
      using a SPF less than 30. Knowledge of risk of skin cancer is better amongst the
      golfers surveyed when compared to the general population. Most respondents (N =
      96 (59%)) were aware that melanoma can lead to death if left untreated and 114
      (70%) recognized that melanoma can be cured if treated early. Conclusion Golfers
      may benefit from targeted education emphasizing the importance of higher SPF use.
      Other interventions that may benefit this population would include availability
      of sunscreens and educational literature in 'pro' shops at golf courses.

PMID- 29169003
TI  - Growing Old in the Emergency Department.
AB  - The research team were concerned that older patients requiring emergency
      admission seemed to wait longer for a hospital bed, and as such were
      disproportionately affected by Emergency Department overcrowding. To investigate
      this theory and explore any changes over time, a ten year dataset (2005-2014
      inclusive) was extracted from the information systems at Beaumont Hospital,
      Dublin. This research examines the changing age profile of ED patients,
      identifies the relationship between age and the total time spent in the Emergency
      Department (Patient Experience Time (PET)), and examines the public belief that
      EDs are busiest in winter when reports of overcrowding and elderly patients
      waiting on trolleys get most media attention. The results highlight that the ED
      is busy all year round (but for different seasonal reasons) and point to an
      overdue need to plan for the current and future healthcare of older patients
      within and beyond acute hospitals.

PMID- 29169004
TI  - Idiopathic Atypical Haemolytic Uraemic Syndrome presenting with acute dystonia.
AB  - Hemolytic Uremic Syndrome (HUS), a triad of microangiopathic hemolytic anemia,
      thrombocytopenia and acute kidney injury. The atypical HUS (aHUS) results from
      over activation of complement system with formation of micro thrombi and damage
      to endothelial cells resulting in renal impairment in 50 % and death in 25 %,
      commonly in untreated patients. We report an intriguing case of aHUS presenting
      with acute onset of movement disorder and fluctuating delirium.

PMID- 29169005
TI  - Atresia Hymenalis with Haematometrocolpos: A Benefit of Teaching a Case Series
      and Review of the Literature.
AB  - We present four cases of atresia hymenalis with resultant haematometrocolpos
      diagnosed in quick succession in the emergency department with a literature
      review.

PMID- 29169006
TI  - Antimicrobial-resistant Faecal Organisms in Algae Products Marketed as Health
      Supplements.
AB  - Dietary supplements are increasingly popular in Irish society. One of these is
      blue-green algae which is used with a variety health benefits in mind. A batch of
      Chlorella powder was found to be contaminated with Salmonella species in Ireland
      in 2015. This prompted additional testing of a total of 8 samples of three
      different products (Chlorella, Spirulina and Super Greens), for other faecal
      flora and antimicrobial resistance in any bacteria isolated. All 8 samples
      cultured enteric flora such as Enterococci, Enterobacteriaceae and Clostridium
      species. Antimicrobial susceptibility testing revealed one isolate with extended
      spectrum ?-lactamase (ESBL) activity and one with carbapenemase activity.
      Clinicians caring for vulnerable patients should be aware of the potential risk
      of exposure to antimicrobial resistant bacteria associated with these products.

PMID- 29169007
TI  - Cold Case Files: 15 years on, did patient controlled analgesia mask acute
      compartment syndrome?

PMID- 29169008
TI  - Erratum to: Isolation, Purification, and Characterization of Five Active
      Diketopiperazine Derivatives from Endophytic Streptomyces SUK 25 with
      Antimicrobial and Cytotoxic Activities.
AB  - This erratum is being published to correct the 2nd author's name of above
      manuscript by Alshaibani et al. that was published in Journal of Microbiology and
      Biotechnology (2017, 27: 1249-1256). The 2nd author name(Noraziah MohamadZin)
      should appear as 'Noraziah Mohamad Zin'.

PMID- 29169009
TI  - Serious incidents after death: content analysis of incidents reported to a
      national database.
AB  - Objectives To describe serious incidents occurring in the management of patient
      remains after their death. Design Incidents occurring after patient deaths were
      analysed using content analysis to determine what happened, why it happened and
      the outcome. Setting The Strategic Executive Information System database of
      serious incidents requiring investigation occurring in the National Health
      Service in England. Participants All cases describing an incident that occurred
      following death, regardless of the age of the patient. Main outcome measures The
      nature of the incident, the underlying cause or causes of the incident and the
      outcome of the incident. Results One hundred and thirty-two incidents were
      analysed; these related to the storage, management or disposal of deceased
      patient remains. Fifty-four incidents concerned problems with the storage of
      bodies or body parts. Forty-three incidents concerned problems with the
      management of bodies, including 25 errors in postmortem examination, or
      postmortems on the wrong body. Thirty-one incidents related to the disposal of
      bodies, 25 bodies were released from the mortuary to undertakers in error; of
      these, nine were buried or cremated by the wrong family. The reported underlying
      causes were similar to those known to be associated with safety incidents
      occurring before death and included weaknesses in or failures to follow protocol
      and procedure, poor communication and informal working practices. Conclusions
      Serious incidents in the management of deceased patient remains have significant
      implications for families, hospitals and the health service more broadly. Safe
      mortuary care may be improved by applying lessons learned from existing patient
      safety work.

PMID- 29169010
TI  - Oxidative stress burden inhibits spermatogenesis in adult male rats: testosterone
      protective effect.
AB  - In this study, we aimed to investigate the protective effects of androgens, using
      letrozole (LET; an aromatase inhibitor), grape seed extract (GSE; a naturally
      occurring aromatase inhibitor and antioxidant), and testosterone propionate (Tp),
      against methotrexate (MTX)-induced testicular toxicity in adult male rats. MTX
      has been shown to induce oxidative stress and exhibit antiproliferative effects
      in the testes. Adult male rats received oral saline gavage (control group with no
      treatment), the potential protective agents (LET, GSE, or Tp) alone, MTX alone,
      or a combination of one of the potential protective agents and MTX. The
      testicular levels of oxidative stress markers and cytokines (tumor necrosis
      factor-alpha and interleukin-1beta) were measured. Spermatogenesis and sperm
      viability were microscopically evaluated. Administration of LET and GSE 7 days
      before MTX improved spermatogenesis and sperm viability, as well as reduced the
      levels of oxidative stress markers and cellular cytokines. Exogenous testosterone
      exhibited anti-inflammatory and antioxidant activities, similar to GSE and LET.
      We also showed that enhancing the endogenous androgenic activity by LET and GSE
      protected spermatogenesis against MTX-induced testicular toxicity via reduction
      of inflammation and oxidative stress in the testes. Our data suggest that
      testosterone protected spermatogenesis owing to its antioxidant and anti
      inflammatory properties.

PMID- 29169011
TI  - Objective and subjective measures of exercise intensity during thermo-neutral and
      hot yoga.
AB  - While hot yoga has gained enormous popularity in recent years, owing in part to
      increased environmental challenge associated with exercise in the heat, it is not
      clear whether hot yoga is more vigorous than thermo-neutral yoga. Therefore, the
      aim of this study was to determine objective and subjective measures of exercise
      intensity during constant intensity yoga in a hot and thermo-neutral environment.
      Using a randomized, crossover design, 14 participants completed 2 identical ~20
      min yoga sessions in a hot (35.3 +/- 0.8  degrees C; humidity: 20.5% +/- 1.4%)
      and thermo-neutral (22.1 +/- 0.2  degrees C; humidity: 27.8% +/- 1.6%)
      environment. Oxygen consumption and heart rate (HR) were recorded as objective
      measures (percentage of maximal oxygen consumption and percentage of maximal HR
      (%HRmax)) and rating of perceived exertion (RPE) was recorded as a subjective
      measure of exercise intensity. There was no difference in exercise intensity
      based on percentage of maximal oxygen consumption during hot versus thermo
      neutral yoga (30.9% +/- 2.3% vs. 30.5% +/- 1.8%, p = 0.68). However, exercise
      intensity was significantly higher during hot versus thermo-neutral yoga based on
      %HRmax (67.0% +/- 2.3% vs. 60.8% +/- 1.9%, p = 0.01) and RPE (12 +/- 1 vs. 11 +/-
      1, p = 0.04). According to established exercise intensities, hot yoga was
      classified as light-intensity exercise based on percentage of maximal oxygen
      consumption but moderate-intensity exercise based on %HRmax and RPE while thermo
      neutral yoga was classified as light-intensity exercise based on percentage of
      maximal oxygen uptake, %HRmax, and RPE. Despite the added hemodynamic stress and
      perception that yoga is more strenuous in a hot environment, we observed similar
      oxygen consumption during hot versus thermo-neutral yoga, classifying both
      exercise modalities as light-intensity exercise.

PMID- 29169012
TI  - Methicillin-resistant Staphylococcus aureus isolated from an intensive care unit
      in Minas Gerais, Brazil, over a six-year period.
AB  - To characterize methicillin-resistant Staphylococcus aureus isolates from an
      intensive care unit of a tertiary-care teaching hospital, between 2005 and 2010.
      A total of 45 isolates were recovered from patients admitted to the intensive
      care unit in the study period. Resistance rates higher than 80% were found for
      clindamycin (100%), erythromycin (100%), levofloxacin (100%), azithromycin
      (97.7%), rifampin (88.8%), and gentamycin (86.6%). The SCCmec typing revealed
      that the isolates harbored the types III (66.7%), II (17.8%), IV (4.4%), and I
      (2.2%). Four (8.9%) isolates carried non-typeable cassettes. Most (66.7%) of the
      isolates were related to the Brazilian endemic clone from CC8/SCCmec III, which
      was prevalent (89.3%) between 2005 and 2007, while the USA100/CC5/SCCmec II
      lineage emerged in 2007 and was more frequent in the last few years. The study
      showed high rates of antimicrobial resistance among methicillin-resistant S.
      aureus isolates and the replacement of Brazilian clone, a well-established
      hospital lineage, by the USA100 in the late 2000s, at the intensive care unit
      under study.

PMID- 29169014
TI  - Editorial Comment.

PMID- 29169015
TI  - Reflections on Covers.

PMID- 29169013
TI  - Body mass index and risk of dementia: Analysis of individual-level data from 1.3
      million individuals.
AB  - INTRODUCTION: Higher midlife body mass index (BMI) is suggested to increase the
      risk of dementia, but weight loss during the preclinical dementia phase may mask
      such effects. METHODS: We examined this hypothesis in 1,349,857 dementia-free
      participants from 39 cohort studies. BMI was assessed at baseline. Dementia was
      ascertained at follow-up using linkage to electronic health records (N = 6894).
      We assumed BMI is little affected by preclinical dementia when assessed decades
      before dementia onset and much affected when assessed nearer diagnosis. RESULTS:
      Hazard ratios per 5-kg/m2 increase in BMI for dementia were 0.71 (95% confidence
      interval = 0.66-0.77), 0.94 (0.89-0.99), and 1.16 (1.05-1.27) when BMI was
      assessed 10 years, 10-20 years, and >20 years before dementia diagnosis.
      CONCLUSIONS: The association between BMI and dementia is likely to be
      attributable to two different processes: a harmful effect of higher BMI, which is
      observable in long follow-up, and a reverse-causation effect that makes a higher
      BMI to appear protective when the follow-up is short.

PMID- 29169016
TI  - Principles of Systems Biology, No. 23.
AB  - This month: protein engineering (Mootha, Chica), synthetic biology (Khalil, You,
      Ting Lu, Timothy K. Lu), microbial ecology and evolution (Desai), side-stepping
      antibiotic resistance (Chandrasekaran), and mapping microbiomes (Borisy).

PMID- 29169017
TI  - Looking Beyond the Stop Sign: Cell-Cycle Checkpoints Reconsidered.
AB  - A quantitative approach that tunes DNA damage strength and observes cell-cycle
      kinetics in single, unperturbed cells yields a new framework for thinking about
      cell-cycle checkpoints.

PMID- 29169018
TI  - Tunable NF-kappaB Oscillations in Yeast.
AB  - Studies of genetic networks in situ are confounded by unknown interactions with
      native networks. In Zhang et al. (2017), the authors capitalize on the fact that
      yeast lacks the NF-kappaB pathway to study the human NF-kappaB pathway in
      isolation and develop a predictive model.

PMID- 29169019
TI  - Dissecting the Ecology of Microbes Using a Systems Toolbox.
AB  - Study of simplified microbial consortia shows that nitrogen overflow by yeast is
      a mechanism that supports the stable co-existence of yeasts and lactic acid
      bacteria.

PMID- 29169020
TI  - Biomarkers of antibiotic resistance genes during seasonal changes in wastewater
      treatment systems.
AB  - To evaluate the seasonal distribution of antibiotic resistance genes (ARGs) and
      explore the reason for their patterns in different seasons and different systems,
      two wastewater treatment systems were selected and analyzed using high-throughput
      qPCR. Linear discriminant analysis (LDA) effect size (LEfSe) was used to discover
      the differential ARGs (biomarkers) and estimate the biomarkers' effect size. We
      found that the total absolute abundances of ARGs in inflows and excess sludge
      samples had no obvious seasonal fluctuations, while those in winter outflow
      samples decreased in comparison with the inflow samples. Eleven differentially
      abundant ARGs (biomarker genes, BmGs) (aadA5-02, aac-6-II, cmlA1-01, cmlA1-02,
      blaOXA10-02, aadA-02, tetX, aadA1, ereA, qacEDelta1-01, and blaTEM) in summer
      samples and 10 BmGs (tet-32, tetA-02, aacC2, vanC-03, aac-6-I1, tetE, ermB, mefA,
      tnpA - 07, and sul2) in winter samples were validated. According to 16S rRNA gene
      sequencing, the relative abundance of bacteria at the phylum level exhibited
      significant seasonal changes in outflow water (OW), and biomarker bacteria (BmB)
      were discovered at the family (or genus) level. Synechococcus and vadinCA02 are
      BmB in summer, and Trichococcus, Lactococcus, Pelosinus, Janthinobacterium,
      Nitrosomonadaceae and Sterolibacterium are BmB in winter. In addition, BmB have
      good correlations with BmGs in the same season, which indicates that bacterial
      community changes drive different distributions of ARGs during seasonal changes
      and that LEfSe is an acute and effective method for finding significantly
      different ARGs and bacteria between two or more classes. In conclusion, this
      study demonstrated the seasonal changes of BmGs and BmB at two wastewater
      treatment systems.

PMID- 29169021
TI  - Is interference control in children with specific language impairment similar to
      that of children with autistic spectrum disorder?
AB  - AIMS: The purpose of the study was to examine resistance to proactive
      interference, which is strongly associated with working memory (WM) performance
      and language processing, in children with specific language impairment (SLI),
      with autism spectrum disorder (ASD), and with typical development (TD). METHODS:
      Sixty children (eight to ten years; matched in age and nonverbal IQ) participated
      in the study. Resistance to proactive interference was measured using a verbal
      conflict paradigm. RESULTS: Children with SLI and ASD show a deficit in
      resistance to proactive interference compared to their TD peers, but the source
      of the problem appears to be different for the two clinical groups. The
      interference problem exhibited by the children with SLI is related to a more
      complex deficit involving different cognitive-linguistic functions, whereas the
      children with ASD show a specific problem in cognitive flexibility. IMPLICATIONS:
      The theoretical implications are that poor resistance to interference may be
      caused by weaknesses in different WM functions, such as a deficit in updating or
      responses based on familiarity rather than recollection. The clinical
      implications are that children with SLI and ASD show distinct patterns of
      performance; therefore they need different types of intervention to strengthen
      their resistance to proactive interference.

PMID- 29169022
TI  - Porous microspheres of polyaniline, poly(o-toluidine), and poly(m-toluidine)
      prepared from double emulsions stabilized by toluidine isomers as the single
      surfactant.
AB  - HYPOTHESIS: Porous spheres of the conducting polymer polyaniline (PANI) and its
      derivatives are promising materials for use as functional encapsulants for
      payload delivery and catalyst supports. Stable water-in-oil-in water (W/O/W)
      double emulsions can be used to obtain this morphology, but typically require
      multiple surfactants and stabilizers. A single surfactant system that uses a
      small amphiphilic molecule is desirable, as it can simplify the method, improve
      its efficiency, and reduce its cost. EXPERIMENTS: Granular poly(o-toluidine)
      (POT) was transformed into porous microspheres when ammonium hydroxide was added
      to an aqueous acidic dispersion containing the preformed polymer and amphiphilic
      o-toluidine (OT). The OT, POT, and ammonium hydroxide concentrations were varied
      to understand the formation mechanism. Conditions were optimized to obtain a
      narrowed size distribution. FINDINGS: The rapid change from acidic to alkaline
      surroundings produces a W/O/W double emulsion from POT and OT over a relatively
      narrow concentration range. Spheres form when POT dissolves in immiscible OT
      droplets, and entrapped water droplets form the pores. OT serves as the single
      amphiphilic surfactant and dissolved POT serves as a hydrophobic co-stabilizer. o
      Toluidine, m-toluidine, or p-toluidine could be used as the single surfactant to
      obtain porous spheres from preformed POT, PANI and poly(m-toluidine).

PMID- 29169023
TI  - Wearable high-performance supercapacitors based on Ni-coated cotton textile with
      low-crystalline Ni-Al layered double hydroxide nanoparticles.
AB  - Wearable electronics are developing rapidly in recent years. In this work, we
      develop a cost-effective, facile, and scalable approach to transform insulating
      cotton textile to highly conductive Ni-coated cotton textile (NCT). In order to
      verify the feasibility of NCT as a flexible current collector for wearable
      supercapacitors, we electrodeposit low-crystalline Ni-Al layered double hydroxide
      (LDH) nanoparticles onto the NCT. The obtained NCT@NiAl-LDH shows high specific
      capacitance (935.2 mF cm-2), superior rate capability, and good cyclability.
      Besides, the asymmetric supercapacitor (ASC) assembled from NCT@NiAl-LDH exhibits
      high specific energy of 58.8 Wh kg-1 (134 MUWh cm-2) when the specific power is
      539 W kg-1 (1228 MUW cm-2). The results demonstrate great potential of our
      methodology.

PMID- 29169024
TI  - Self-cleaning superhydrophobic epoxy coating based on fibrous silica-coated iron
      oxide magnetic nanoparticles.
AB  - Inspired by the self-cleaning lotus leaf, a facile method of fabricating
      superhydrophobic silica coated magnetite nanoparticles using a cost-effective
      process is presented in this work. The structural characterizations and magnetic
      properties of the obtained core-shell magnetic nanoparticles were characterized
      by means of X-ray diffraction (XRD), thermal gravimetric analysis (TGA), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating
      sample magnetometer (VSM). TEM analysis revealed that the particles present
      flower-like dendrimeric fibers morphology. The particles were uniformly dispersed
      on the surface of an epoxy resin coating with the purpose to increase the
      roughness and reduce the surface energy of the surface. The resulting
      superhydrophobic surface provides robust water-repellent surface under harsh
      conditions, thanks to its self-cleaning characteristic. The superhydrophobicity
      of this surface was confirmed based on the measurements of a water contact angle
      around 175 degrees , which surpasses the theoretical limit of the
      superhydrophobicity. The simplicity and the cost-effectiveness of the process
      developed in this study appears to be a promising route for the preparation of
      other magnetic superhydrophobic organic-inorganic hybrid materials that would be
      beneficial in a wide variety of applications.

PMID- 29169025
TI  - Foam and thin films of hydrophilic silica particles modified by beta-casein.
AB  - HYPOTHESIS: Foaming properties of particle dispersions can be modified by
      addition of amphiphiles. The molar ratio between particles and amphiphiles will
      influence the wetting properties of the particles as well as the bulk
      concentration of the amphiphiles. This will have an effect on air/water
      interfacial composition as well as on the thin film and foam stability of the
      mixed system. EXPERIMENTS: In this research foams and thin films of hydrophilic
      silica particles in presence of beta-casein (beta-CN) were investigated with
      different particle sizes and varying beta-CN/silica weight ratios (between 1:10
      and 1:100). Samples were characterized for particles size, morphology as well as
      contact angle and related to their foaming, interfacial, and thin film
      properties. FINDINGS: A threshold weight ratio of beta-CN/silica was found to be
      1:50 for foam stabilization with mixtures containing silica particles no larger
      than 1 MUm and 1:30 for film stabilization with mixtures containing larger
      particles. At the interface, the modified silica particles were rather diluted
      without much interaction for surface compressions up to 30%. Large silica
      particles (0.0015% beta-CN, Csilica <= 0.15%) were dragged to the periphery of
      the thin liquid films but no decrease of the inner film draining rate by a
      decrease of capilary pressure gradient across the film was observed. The
      depletion of beta-casein in the bulk by particles played a major role in foam
      destabilization.

PMID- 29169027
TI  - Phase modulated 2D HSQC-TOCSY for unambiguous assignment of overlapping spin
      systems.
AB  - We present a new method that allows one to unambiguously resolve overlapping spin
      systems often encountered in biomolecular systems such as peptides and proteins
      or in samples containing a mixture of different molecules such as in
      metabolomics. We address this problem using the recently proposed phase
      modulation approach. By evolving the 1H chemical shifts in a conventional two
      dimensional (2D) HSQC-TOCSY experiment for a fixed delay period, the
      phase/intensity of set of cross peaks belonging to one spin system are modulated
      differentially relative to those of its overlapping counterpart, resulting in
      their discrimination and recognition. The method thus accelerates the process of
      identification and resonance assignment of individual compounds in complex
      mixtures. This approach facilitated the assignment of molecules in the embryo
      culture medium used in human assisted reproductive technology.

PMID- 29169026
TI  - Structures and mechanisms in clay nanopore trapping of structurally-different
      fluoroquinolone antimicrobials.
AB  - Smectite clay nanoparticles are implicated in the retention of antimicrobials
      within soils and sediments; these clays are also inspected as drug carriers in
      physiological systems. Cation exchange is considered the primary adsorption
      mechanism of antimicrobials within smectite nanopores. However, a dual role of
      acid-base chemistry and adsorptive structures is speculated by recent studies.
      Using the prototypical smectite clay montmorillonite, we employed a combination
      of X-ray diffraction (XRD), nuclear magnetic resonance, attenuated total
      reflectance-Fourier transform infrared spectroscopy, and molecular dynamics
      simulations to investigate the interlayer nanopore trapping of two structurally
      different fluoroquinolone (FQ) antimicrobials with similar acid-base chemistry:
      ciprofloxacin (a first-generation FQ) and moxifloxacin (a third-generation FQ).
      Greater sorption at pH 5.0 than at pH 7.0 for both FQs was consistent with cation
      exchange of positively-charged species. However, the clay exhibited a near
      twofold higher sorption capacity for moxifloxacin than for ciprofloxacin. This
      difference was shown by the XRD data to be accompanied by enhanced trapping of
      moxifloxacin within the clay interlayers. Using the XRD-determined nanopore
      sizes, we performed molecular dynamics simulations of thermodynamically-favorable
      model adsorbates, which revealed that ciprofloxacin was adsorbed parallel to the
      clay surface but moxifloxacin adopted a tilted conformation across the nanopore.
      These conformations resulted in more slowly-exchanged than quickly-exchanged Na
      complexes with ciprofloxacin compared with moxifloxacin. These different Na
      populations were also captured by 23Na nuclear magnetic resonance. Furthermore,
      the simulated adsorbates uncovered different complexation interactions that were
      corroborated by infrared spectroscopy. Therefore, beyond acid-base chemistry, our
      findings imply that distinct adsorbate structures control antimicrobial trapping
      within clay nanopores, which can promote persistence in environmental matrices
      and stable delivery in biological systems.

PMID- 29169028
TI  - Relationships of depression and anxiety symptoms with seizure frequency: Results
      from a multicenter follow-up study.
AB  - PURPOSE: Depressive and anxiety disorders are frequent among people with
      epilepsies. There are, however, only few longitudinal studies, which examine the
      relationship between these comorbid psychiatric disorders and epilepsy-related
      variables. Thus, we investigated the interrelationships of depression and anxiety
      symptoms with seizure frequency across time. METHODS: Before admittance to an
      epilepsy center (T1) and six months after discharge (T2), patients (n=198) with
      mainly difficult-to-treat epilepsies completed the Hospital Anxiety and
      Depression Scale (HADS). Correlation and path analyses were conducted. RESULTS:
      Depression and anxiety symptoms (HADS) as well as seizure frequency significantly
      decreased from baseline to follow-up. Both at T1 and T2, seizure frequency was
      slightly, but significantly correlated with depression and anxiety levels (rs
      CONCLUSION: The present findings emphasize the importance of psychiatric
      comorbidities, especially depression, for seizure frequency and its progress in
      patients with difficult-to-treat epilepsies referred to a specialized epilepsy
      center. Thus, comorbid psychiatric disorders need specific consideration as part
      of a comprehensive diagnostic and therapeutic treatment approach.

PMID- 29169029
TI  - Learning normalized inputs for iterative estimation in medical image
      segmentation.
AB  - In this paper, we introduce a simple, yet powerful pipeline for medical image
      segmentation that combines Fully Convolutional Networks (FCNs) with Fully
      Convolutional Residual Networks (FC-ResNets). We propose and examine a design
      that takes particular advantage of recent advances in the understanding of both
      Convolutional Neural Networks as well as ResNets. Our approach focuses upon the
      importance of a trainable pre-processing when using FC-ResNets and we show that a
      low-capacity FCN model can serve as a pre-processor to normalize medical input
      data. In our image segmentation pipeline, we use FCNs to obtain normalized
      images, which are then iteratively refined by means of a FC-ResNet to generate a
      segmentation prediction. As in other fully convolutional approaches, our pipeline
      can be used off-the-shelf on different image modalities. We show that using this
      pipeline, we exhibit state-of-the-art performance on the challenging Electron
      Microscopy benchmark, when compared to other 2D methods. We improve segmentation
      results on CT images of liver lesions, when contrasting with standard FCN
      methods. Moreover, when applying our 2D pipeline on a challenging 3D MRI prostate
      segmentation challenge we reach results that are competitive even when compared
      to 3D methods. The obtained results illustrate the strong potential and
      versatility of the pipeline by achieving accurate segmentations on a variety of
      image modalities and different anatomical regions.

PMID- 29169030
TI  - Lipoprotein-associated phospholipase A2 and risk of incident peripheral arterial
      disease: Findings from The Atherosclerosis Risk in Communities study (ARIC).
AB  - BACKGROUND AND AIMS: Results from prospective studies evaluating the relationship
      between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and
      incident peripheral arterial disease (PAD) have been mixed. We investigated
      whether higher Lp-PLA2 levels are associated with increased risk of incident PAD
      and whether PLA2G7 gene variants, which result in lower Lp-PLA2 levels, are
      associated with reduced risk of incident PAD. METHODS: Our analysis included 9922
      participants (56% female; 21% African-American; mean age 63 years) without
      baseline PAD at ARIC Visit 4 (1996-1998), who had Lp-PLA2 activity measured and
      were subsequently followed for the development of PAD, defined by occurrence of a
      PAD-related hospitalization, through 2012. Cox proportional hazard models were
      performed to determine the association of Lp-PLA2 levels and PLA2G7 gene variants
      with incident PAD. RESULTS: During a median follow-up of 14.9 years, we
      identified 756 incident cases of PAD. In analyses adjusting for age, race, and
      sex, each standard deviation increment in Lp-PLA2 activity (62 nmol/ml/min) was
      associated with a higher risk of developing PAD (hazard ratio (HR) 1.17; 95%
      confidence interval (CI) 1.09, 1.26). This association remained significant after
      additional adjustment for risk factors, other cardiovascular disease, and
      medication use, but was strongly attenuated (HR: 1.09; 95% CI 1.00, 1.20). PLA2G7
      variants were not associated with a lower risk of PAD in both white carriers (HR:
      1.21; 95% CI: 0.17-8.56) and African-American carriers (HR: 0.83; 95% CI: 0.41
      1.67), although statistical power was quite limited for this analysis,
      particularly in whites. CONCLUSIONS: While higher Lp-PLA2 activity was associated
      with an increased risk for incident PAD, it is likely a risk marker largely
      represented by traditional risk factors.

PMID- 29169031
TI  - Visceral fat index/percentage body fat ratio is independently associated with
      proximal aortic dilatation in a middle-aged and aged Chinese population in
      Liujiang of Guangxi.
AB  - BACKGROUND AND AIMS: Increased volume of visceral adipose tissue is associated
      with worsening of cardiovascular disease risk factors that contribute to aortic
      dilatation. We investigated the effects of visceral fat index (VFI) and
      VFI/percentage body fat (PBF) ratio on proximal aortic size and proximal aortic
      dilatation (PAD), to assess whether excess visceral fat deposition is an
      independent risk factor for PAD. METHODS: 738 participants aged 35 years or more
      were included in this cross-sectional survey. The sizes of aortic valve annulus
      (AVA), sinuses of Valsalva (SV), sinotubular junction (STJ), and ascending aorta
      (AscAo) were measured by transthoracic ultrasound. Multivariate linear
      regression, binary logistic regression, Bayesian linear regression, and receiver
      operating characteristic curves were performed to clarify the effects of VFI and
      VFI/PBF ratio on PAD. RESULTS: There were 78 participants (10.6%) with PAD. VFI
      and VFI/PBF ratio in the population with PAD was significantly increased,
      compared to the population without PAD (p < 0.001). However, PBF was not
      significantly different between the two populations. VFI/PBF ratio was positively
      associated with sizes of AVA, SV, STJ, and AscAo (p < 0.05), and was
      independently related to PAD (p < 0.05). A 1-SD increment in VFI/PBF ratio was
      associated with 13.35-fold increased risk of PAD (odds ratio: 13.35, p < 0.05).
      CONCLUSIONS: VFI/PBF ratio is independently associated with PAD. An increased
      proportion of visceral fat may contribute to PAD. VFI/PBF ratio calculation may
      be used for the preliminary identification of individuals at high risk of PAD in
      the Chinese population.

PMID- 29169032
TI  - Altering movement parameters disrupts metacognitive accuracy.
AB  - Correctly estimating the confidence we should have in our decisions has
      traditionally been viewed as a perceptual judgement based solely on the strength
      or quality of sensory information. However, accumulating evidence has
      demonstrated that the motor system contributes to judgements of perceptual
      confidence. Here, we manipulated the speed at which participants' moved using a
      behavioural priming task and showed that increasing movement speed above
      participants' baseline measures disrupts their ability to form accurate
      confidence judgements about their performance. Specifically, after being primed
      to move faster than they would naturally, participants reported higher confidence
      in their incorrect decisions than when they moved at their natural pace. We refer
      to this finding as the adamantly wrong effect. The results are consistent with
      the hypothesis that veridical feedback from the effector used to indicate a
      decision is employed to form accurate metacognitive judgements of performance.

PMID- 29169033
TI  - Mapping complex mind states: EEG neural substrates of meditative unified
      compassionate awareness.
AB  - Specific mental training cultivates diminished self-reference, encompassing non
      duality, emptiness, awakened-awareness, and compassionate experiences. We aimed
      to elucidate the neural substrates of four distinct, interdependent Essence-of
      Mind states: (1) timelessness, (2) non-preference, non-duality, non
      conceptualization, (3) the view of luminosity and limitlessness, (4) unified
      compassionate experience of oneness (stable awakened-awareness). EEG data were
      collected from 30 advanced meditators concomitant to eyes-open/eyes-closed
      resting baseline, followed by 60-min of instructed practice. Alpha, beta, and
      gamma, frequency-spatial EEG-dimensions were analyzed. The results revealed that
      compared to baseline, current density across frequencies significantly decreased
      upon meditation onset in self-referential, and executive-control regions. During
      meditation, gamma-band current density significantly increased from state-1
      compared to state-4, within the ACC, precuneus, and superior parietal lobule,
      whereas beta-band activity increased within the insula. These findings suggest a
      dissociation between brain regions regulating self-referential vs. executive
      control processing, during non-dual, compassionate states, characterized by
      brilliantly awake awareness, free from conceptual thought and "doing".

PMID- 29169034
TI  - Greater cortical thickness within the limbic visceromotor network predicts higher
      levels of trait emotional awareness.
AB  - Previous studies of trait emotional awareness (EA) have not yet examined whether
      differences in cortical structure might account for differences in EA. Based on
      previous research on the relationship between EA and both emotion
      conceptualization and visceromotor control processes, we tested two hypotheses in
      a sample of 26 healthy participants: that higher EA would be predicted by greater
      cortical thickness within (1) regions of the default mode network (DMN; linked
      with conceptualization processes), and/or (2) regions of the limbic network
      (linked with affect generation and visceromotor control processes). A non
      significant correlation was found between EA and cortical thickness in the DMN.
      In contrast, a significant positive correlation was observed between EA and
      cortical thickness within the limbic network. These findings suggest that the
      structural integrity of cortical regions involved in the generation of affective
      bodily reactions may play a more important role in explaining differences in EA
      than previously thought.

PMID- 29169036
TI  - Frequency of lethal means assessment among emergency department patients with a
      positive suicide risk screen.
AB  - Prior work from surveys and limited populations suggests many emergency
      department (ED) patients with suicide risk do not have documented lethal means
      assessments (e.g., being asked about home firearms). The specific objectives of
      this study were to, in an ED with universal screening for suicide risk: (1)
      estimate how often ED providers documented lethal means assessment for suicidal
      patients, and (2) compare patients with and without documented lethal means
      assessments. We reviewed 800 total charts from a random sample of adults in three
      a priori age groups (18-34 years; 35-59 years; >= 60 years) with a positive
      suicide risk screen from 8/2014 to 12/2015. Only 18% (n = 145) had documentation
      by >= 1 provider of assessment of lethal means access. Among these 145, only 8%
      (n = 11) had documentation that someone discussed an action plan to reduce access
      (most commonly changing home storage or moving objects out of the home). Among
      545 suicidal patients discharged home from the ED, 85% had no documentation that
      any provider assessed access to lethal means. Our findings highlight an important
      area for improving care: routine, documented lethal means assessment and
      counseling for patients with suicide risk. There is an urgent need for further
      exploration of barriers and facilitators.

PMID- 29169035
TI  - Do law enforcement interactions reduce the initiation of injection drug use? An
      investigation in three North American settings.
AB  - BACKGROUND: The prevention of drug injecting is often cited as a justification
      for the deployment of law enforcement and for the continuation of drug
      criminalization policies. We sought to characterize the impact of law enforcement
      interactions on the risk that people who inject drugs (PWID) report assisting
      others with injection initiation in three North American countries. METHODS:
      Cross-sectional data from PWID participating in cohort studies in three cities
      (San Diego, USA; Tijuana, Mexico; Vancouver, Canada) were pooled (August 2014
      December 2016). The dependent variable was defined as recently (i.e., past six
      months) providing injection initiation assistance; the primary independent
      variable was the frequency of recent law enforcement interactions, defined
      categorically (0 vs. 1 vs. 2-5 vs. >=6). We employed multivariable logistic
      regression analyses to assess this relationship while controlling for potential
      confounders. RESULTS: Among 2122 participants, 87 (4.1%) reported recently
      providing injection initiation assistance, and 802 (37.8%) reported recent law
      enforcement interactions. Reporting either one or more than five recent
      interactions with law enforcement was not significantly associated with injection
      initiation assistance. Reporting 2-5 law enforcement interactions was associated
      with initiation assistance (Adjusted Odds Ratio=1.74, 95% Confidence Interval:
      1.01-3.02). CONCLUSIONS: Reporting interactions with law enforcement was not
      associated with a reduced likelihood that PWID reported initiating others into
      injection drug use. Instead, we identified a positive association between
      reporting law enforcement interactions and injection initiation assistance among
      PWID in multiple settings. These findings raise concerns regarding the
      effectiveness of drug law enforcement to deter injection drug use initiation.

PMID- 29169037
TI  - A nephron model for study of drug-induced acute kidney injury and assessment of
      drug-induced nephrotoxicity.
AB  - In this study, we developed a multilayer microfluidic device to simulate nephron,
      which was formed by "glomerulus", "Bowman's capsule", "proximal tubular lumen"
      and "peritubular capillary". In this microdevice, artificial renal blood flow was
      circulating and glomerular filtrate flow was single passing through, mimicking
      the behavior of a nephron. In this dynamic artificial nephron, we observed
      typical renal physiology, including the glomerular size-selective barrier,
      glomerular basement membrane charge-selective barrier, glucose reabsorption and
      para-aminohippuric acid secretion. To demonstrate the capability of our
      microdevice, we used it to investigate the pathophysiology of drug-induced acute
      kidney injury (AKI) and give assessment of drug-induced nephrotoxicity, with
      cisplatin and doxorubicin as model drugs. In the experiment, we loaded the
      doxorubicin or cisplatin in the "renal blood flow", recorded the injury of
      primary glomerular endothelial cells, podocytes, tubular epithelial cells and
      peritubular endothelial cells by fluorescence imaging, and identified the time
      dependence, dose-dependence and the death order of four types of renal cells.
      Then by measuring multiple biomarkers, including E-cadherin, VEGF, VCAM-1,
      Nephrin, and ZO-1, we studied the mechanism of cell injuries caused by
      doxorubicin or cisplatin. Also, we investigated the effect of BSA in the "renal
      blood flow" on doxorubicin-or-cisplatin-induced nephrotoxicity, and found that
      BSA enhanced the tight junctions between cells and eased cisplatin-induced
      nephrotoxicity. In addition, we compared the nephron model and traditional tubule
      models for assessment of drug-induced nephrotoxicity. And it can be inferred that
      our biomimetic microdevice simulated the complex, dynamic microenvironment of
      nephron, yielded abundant information about drug-induced-AKI at the preclinical
      stage, boosted the drug safety evaluation, and provided a reliable reference for
      clinical therapy.

PMID- 29169038
TI  - Theranostic 2D ultrathin MnO2 nanosheets with fast responsibility to endogenous
      tumor microenvironment and exogenous NIR irradiation.
AB  - The fabrication of functional nanoparticles with unique ultra-sensitivity to
      endogenous tumor microenvironment (TME) is of great significance for their
      improved theranostic performance and easy excretion out of the body, which has
      not been realized among diverse nano-sized photothermal agents for photothermal
      therapy (PTT) of tumor. In this work, we report on the synthesis of 2D ultrathin
      MnO2 nanosheets for highly efficient PTT against tumor with ultra-sensitivity to
      endogenous TME. These ultrathin 2D MnO2 nanosheets show the intriguing
      characteristic of disintegration and releasing of Mn2+ in response to the mild
      acidic condition and elevated reducing microenvironment of TME, which has
      successfully realized the pH- and reducing-responsive T1-weighted magnetic
      resonance imaging of tumor. Importantly, the high PTT efficiency of 2D MnO2
      nanosheets responsive to exogenous NIR irradiation has been systematically
      demonstrated both in vitro and in vivo for suppressing the tumor growth. This
      first report on the exploring of TME-sensitive photothermal agents with
      concurrent diagnostic and therapeutic (theranostic) functions significantly
      broadens the biomedical application of 2D functional biomaterials, which also
      promotes the further potential clinical translations of nano-sized photothermal
      agents.

PMID- 29169039
TI  - Heteromultivalent targeting of integrin alphavbeta3 and neuropilin 1 promotes
      cell survival via the activation of the IGF-1/insulin receptors.
AB  - Angiogenesis strongly depends on the activation of integrins, especially integrin
      alphavbeta3, and of neuropilin-1 (NRP-1), a co-receptor of VEGFR2. Dual-targeted
      molecules that simultaneously block both of them are expected have increased anti
      angiogenic and antitumor activity. Toward this goal, we generated bifunctional 40
      nm-sized silica nanoparticles (NPs) coated with controlled amounts of cRGD and
      ATWLPPR peptides and studied their affinity, selectivity and biological activity
      in HUVECs. Sub-nanomolar concentrations of NPs grafted either with ATWLPPR alone
      or in combination with cRGD exhibit potent and specific antagonist activity
      against VEGFR2/AKT signaling. However, a 1 nM concentration of the cRGD/ATWLPPR
      heteromultivalent particles (RGD/ATW-NPs) also blocks the phosphorylation of
      VEGFR2 while co-inducing an unexpected long-lasting activation of AKT via IGF
      1R/IR-AKT/GSK3beta/eNOS signaling that stimulates cell survival and abrogates the
      intrinsic toxicity of silica-NPs to serum-starved HUVECs. We also showed that
      their repeated intravenous administration was associated with the proliferation
      of human U87MG tumor cells engrafted in nude mice and a dilatation of the tumor
      blood vessels. We present biochemical evidence for the complex cross-talk
      generated by the binding of the heteromultivalent NPs with alphavbeta3-integrin
      and with NRP1. In particular, we show for the first time that such
      heteromultivalent NPs can trans-activate IGF-1/insulin receptors and exert dose
      dependent pro-survival activity. This study demonstrates the difficulties in
      designing targeted silica-based NPs for antiangiogenic therapies and the possible
      risks posed by undesirable side effects.

PMID- 29169040
TI  - Tracking and protection of transplanted stem cells using a ferrocenecarboxylic
      acid-conjugated peptide that mimics hTERT.
AB  - In vivo tracking of transplanted stem cells has been a central aim of stem cell
      therapy. Although many tracking systems have been introduced, no method has yet
      been validated for clinical applications. We developed a novel sophisticated
      peptide (GV1001) that mimics hTERT (human telomerase reverse transcriptase) and
      analysed its ability to track and protect stem cells after transplantation.
      Ferrocenecarboxylic acid-conjugated GV1001 (Fe-GV1001) efficiently penetrated
      stem cells with no adverse effects. Moreover, Fe-GV1001 improved the viability,
      proliferation, and migration of stem cells under hypoxia. After Fe-GV1001
      labelled stem cells were transplanted into the brains of rats after stroke, the
      labelled cells were easily tracked by MRI. Our findings indicate that Fe-GV1001
      can be used for the in vivo tracking of stem cells after transplantation into the
      brain and can improve the efficacy of stem cell therapy by sustaining and
      enhancing stem cell characteristics under disease conditions.

PMID- 29169041
TI  - The Shewanella woodyi galactokinase pool phosphorylates glucose at the 6
      position.
AB  - Galactokinases are a class of enzymes which belong to the GHMP (galactokinase,
      homoserine kinase, mevalonate kinase, and phosphomevalonate kinase) superfamily
      and catalyse the phosphorylation of galactose in the first step of the Leloir
      pathway. Here we report the discovery of three enzymes from Shewanella woodyi
      which have been classified as galactokinases based on sequence similarity.
      However, each of these enzymes show little to no significant activity towards
      galactose and instead exhibit a strong preference for glucose. Furthermore, in
      contrast to the usual galactose-1-phosphate product of the galactokinase
      catalysed reaction, these enzymes produce glucose-6-phosphate. This radical
      change in enzyme functionality is postulated to be linked to the mutation of a
      glycine residue which is conserved in all other sequenced galactokinases.

PMID- 29169042
TI  - Synthesis of aromatic and indole alpha-glucosinolates.
AB  - Aromatic and indole glucosinolates are important members of the glucosinolate
      family of compounds du to their potential medicinal properties. They are known to
      exert antioxidant and anti-carcinogenic activity either by the natural products
      themselves, or their metabolic products including indole-3-carbinol and
      isothiocyanates. Natural glucosinolates are all beta-glucosinolates; however,
      alpha-glucosinolates are also promising compounds for medicinal applications and
      hence have to be produced synthetically for any bio-activity studies. Here we
      report on the successful synthesis of a series of alpha-glucosinolates: alpha
      neoglucobrassicin, alpha-4-methoxyglucobrassicin, 2,3-dichlorophenyl-alpha
      glucosinolate for the first time. Testing for anti-inflammatory properties of
      these synthetic GLs, however, did not yield the expected activity.

PMID- 29169043
TI  - Promoting father involvement in early home visiting services for vulnerable
      families: Findings from a pilot study of "Dads matter".
AB  - Despite mounting evidence on the importance of fathers in children's development,
      evidence-based perinatal home visitation programs have largely overlooked fathers
      in the design and delivery of services. This paper describes the design,
      development, and pilot testing of the "Dads Matter" enhancement to standard home
      visiting services. Dads Matter is a manualized intervention package designed to
      fully incorporate fathers into perinatal home visiting services. Twenty-four
      families were enrolled in a pilot study to assess the feasibility, acceptability,
      and preliminary outcomes of the intervention. Using a quasi-experimental time
      lagged design, 12 families received standard home visiting services and completed
      baseline and four-month post-tests. Home visitor staff were then trained and
      supervised to implement the Dads Matter enhancement in addition to standard
      services. Twelve additional families were then enrolled and completed baseline
      and four-month post-tests. Implementation data indicated that Dads Matter was
      implemented as planned. Cohen's d scores on outcome measures indicate positive
      trends associated with Dads Matter in the quality of the mother-father
      relationship, perceived stress reported by both parents, fathers' involvement
      with the child, maltreatment indicators, and fathers' verbalizations toward the
      infant. Effect sizes generally ranged from moderate to large in magnitude and
      were larger than overall effect sizes of home visitation services alone reported
      in prior meta-analyses. Dads Matter appears to be a feasible, acceptable, and
      promising approach to improving fathers' engagement in home visiting services and
      promoting family and child well-being.

PMID- 29169044
TI  - Esculentoside A specifically binds to ribosomal protein S3a and impairs LPS
      induced signaling in macrophages.
AB  - Esculentoside A (EsA), a saponin isolated from Phytolacca esculenta, is reported
      as a potent suppressor of pro-inflammatory functions of macrophages. However,
      little is known about the target proteins of EsA for its anti-inflammatory
      activity. In the present study, to identify the intracellular target for EsA,
      affinity resins bearing immobilized EsA were used to capture binding proteins of
      EsA from RAW264.7 cell lysates. Mass spectrography and Western blot analysis of
      captured proteins indicated that ribosomal protein S3a preferentially bound to
      EsA affinity resin. Competition experiment further demonstrated that free EsA can
      disturb the specific interaction between recombinant RPS3a and affinity resin.
      Surface Plasmon Resonance analysis confirmed that EsA directly bound to RPS3a.
      Lentivirus-mediated RNAi RPS3a resulted in suppression of TNF-alpha and IL-6
      production and impediment of signal transduction in LPS-stimulated RAW264.7
      cells, indicating that RPS3a is required for LPS-triggered signaling during
      induction of pro-inflammatory cytokines. In addition, EsA inhibited the
      expression of inflammatory factors more strongly in the case of RPS3a
      interference. These results suggest that EsA exerts its anti-inflammatory
      activity by targeting RPS3a and impairing its signaling function. These new
      findings not only extended our understanding on the intracellular mechanisms of
      EsA, but also indicated RPS3a as an essential component for LPS-mediated pro
      inflammatory signaling, thus implying RPS3a as a novel therapeutic target for
      anti-inflammatory therapy.

PMID- 29169045
TI  - Optimizing medication use in elderly people in primary care: Impact of STOPP
      criteria on inappropriate prescriptions.
AB  - BACKGROUND: STOPP (Screening Tool of Older Person's Prescriptions) criteria have
      been used in acute care and nursing home settings as a screening tool to assess
      Potentially Inappropriate Medication (PIM) for elderly people. Furthermore, this
      tool could help General Practitioners (GPs) to lower PIM frequency in primary
      care. OBJECTIVE: The aim of the study was to measure the impact of STOPP criteria
      applied by the GP on prescriptions during a primary care consultation. SETTING,
      SUBJECTS AND METHOD: Twenty GPs were involved and trained to use STOPP criteria.
      GPs were asked to use STOPP criteria for elderly patients (>75years old) who were
      taking at least five different drugs, seen over a two-month period. The rate of
      PIM according to STOPP criteria was measured before and after training.
      Prescription quality was compared using the Medication Appropriateness Index
      (MAI) score. RESULTS: Overall, 172 prescriptions were analyzed. A total of 170
      PIM were identified according to STOPP criteria before the intervention. Fifty
      seven percent of the population (n=98 patients) had at least one PIM. GP's
      intervention decreased the number of PIM according to STOPP criteria to 106 and
      was beneficial for 44.9% of the patients (n=44). The mean MAI score of all
      medications and PIM decreased by 14.3% (p<0.001) and 39.1% (p<0.001)
      respectively. DISCUSSION CONCLUSIONS: Application of STOPP criteria by GPs is an
      effective tool to decrease PIM and MAI score in primary care. The generalization
      of the use of STOPP criteria during GP consultation should be fostered.

PMID- 29169046
TI  - A novel CCM1/KRIT1 heterozygous deletion mutation (c.1919delT) in a Chinese
      family with familial cerebral cavernous malformation.
AB  - BACKGROUND: Cerebral cavernous malformation (CCM) is a relatively rare congenital
      vascular anomaly in the central venous system. Its inherited form, familial
      cerebral cavernous malformation (FCCM), is an autosomal-dominant disease with
      incomplete penetrance. The pathogenic genes of FCCM have been mapped into three
      loci: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. Till now, the genetic basis of
      FCCM in the Chinese population has yet to be well understood. Herein, we
      investigated the genetic mutation in a Chinese family with FCCM. CASE REPORT: The
      proband is a 29-year-old female presenting with a 1-month history of headache.
      Brain magnetic resonance imaging (MRI) revealed multiple intracranial lesions,
      the largest one showing a popcorn-like appearance. After a 4-year conservative
      observation, there was no significant clinical or radiological progression.
      Family investigation found five of her relatives had multiple CCM lesions. DNA
      sequencing analysis in the proband disclosed a novel heterozygous deletion
      mutation (c.1919delT; p.Phe640SerfsX21) in exon 17 of the CCM1/KRIT1 gene. This
      mutation leads to a frameshift and is predicted to cause a premature termination
      codon to generate a truncated Krev interaction trapped-1 (Krit1) protein of 659
      amino acids. The mutation segregated with the disease in the family. CONCLUSION:
      The current study identified a novel CCM1/KRIT1 heterozygous deletion mutation
      (c.1919delT) associated with FCCM. Our findings expand the CCM gene mutation
      profiles in the Chinese population, which will be beneficial for genetic
      counseling.

PMID- 29169047
TI  - Spinal muscular atrophy with progressive myoclonic epilepsy linked to mutations
      in ASAH1.
AB  - Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), a rare
      disorder caused by mutation in the ASAH1 gene, is characterized by progressive
      muscle weakness and intractable epilepsy. The literature about SMA-PME is very
      rare and most of the time limited to case reports. Mutation in the ASAH1 gene is
      also found in another rare syndrome which is Farber disease. We report a case of
      a 13.5-year-old girl with SMA-PME associated with ASAH1 gene mutation. She
      presented with progressive muscle weakness, tremor, seizure, and cognitive
      impairment. Clinical features and electrophysiological investigations revealed a
      motor neuron disease and generalized epilepsy. The marked difference in disease
      manifestations may explain why Farber and SMA-PME diseases were not suspected of
      being allelic conditions. SMA-PME cases with ASAH1 mutation could be treated
      using therapeutic studies regarding Farber disease. In patients with undefined
      PME or lower motor neuron disease cases, ASAH1 mutation scans should be studied.

PMID- 29169049
TI  - Stuttering adults' lack of pre-speech auditory modulation normalizes when
      speaking with delayed auditory feedback.
AB  - Auditory modulation during speech movement planning is limited in adults who
      stutter (AWS), but the functional relevance of the phenomenon itself remains
      unknown. We investigated for AWS and adults who do not stutter (AWNS) (a) a
      potential relationship between pre-speech auditory modulation and auditory
      feedback contributions to speech motor learning and (b) the effect on pre-speech
      auditory modulation of real-time versus delayed auditory feedback. Experiment I
      used a sensorimotor adaptation paradigm to estimate auditory-motor speech
      learning. Using acoustic speech recordings, we quantified subjects' formant
      frequency adjustments across trials when continually exposed to formant-shifted
      auditory feedback. In Experiment II, we used electroencephalography to determine
      the same subjects' extent of pre-speech auditory modulation (reductions in
      auditory evoked potential N1 amplitude) when probe tones were delivered prior to
      speaking versus not speaking. To manipulate subjects' ability to monitor real
      time feedback, we included speaking conditions with non-altered auditory feedback
      (NAF) and delayed auditory feedback (DAF). Experiment I showed that auditory
      motor learning was limited for AWS versus AWNS, and the extent of learning was
      negatively correlated with stuttering frequency. Experiment II yielded several
      key findings: (a) our prior finding of limited pre-speech auditory modulation in
      AWS was replicated; (b) DAF caused a decrease in auditory modulation for most
      AWNS but an increase for most AWS; and (c) for AWS, the amount of auditory
      modulation when speaking with DAF was positively correlated with stuttering
      frequency. Lastly, AWNS showed no correlation between pre-speech auditory
      modulation (Experiment II) and extent of auditory-motor learning (Experiment I)
      whereas AWS showed a negative correlation between these measures. Thus, findings
      suggest that AWS show deficits in both pre-speech auditory modulation and
      auditory-motor learning; however, limited pre-speech modulation is not directly
      related to limited auditory-motor adaptation; and in AWS, DAF paradoxically tends
      to normalize their otherwise limited pre-speech auditory modulation.

PMID- 29169048
TI  - Protein lipoylation: an evolutionarily conserved metabolic regulator of health
      and disease.
AB  - Lipoylation is a rare, but highly conserved lysine posttranslational
      modification. To date, it is known to occur on only four multimeric metabolic
      enzymes in mammals, yet these proteins are staples in the core metabolic
      landscape. The dysregulation of these mitochondrial proteins is linked to a range
      of human metabolic disorders. Perhaps most striking is that lipoylation itself,
      the proteins that add or remove the modification, as well as the proteins it
      decorates are all evolutionarily conserved from bacteria to humans, highlighting
      the importance of this essential cofactor. Here, we discuss the biological
      significance of protein lipoylation, the importance of understanding its
      regulation in health and disease states, and the advances in mass spectrometry
      based proteomic technologies that can aid these studies.

PMID- 29169050
TI  - Utility of post mortem computed tomography in clivus fracture diagnosis. Case
      illustration and literature review.
AB  - Clivus fractures are usually associated with head blunt trauma due to traffic
      accident and falls. A 23 - year-old man died immediately after a smash-up while
      he was stopping on his motorcycle. Post-mortem Computed tomography (PMCT),
      performed before autopsy, revealed a complex basilar skull base fractures
      associated with brainstem and cranio-vertebral junction injuries, improving the
      diagnostic performance of conventional autopsy. Imaging data were re-assessable
      and PMCT offers the possibility to perform multiplanar and volume rendered
      reconstructions, increasing forensic medicine knowledge related to traumatic
      injuries.

PMID- 29169051
TI  - Cyanobacteria blooms induce embryonic heart failure in an endangered fish
      species.
AB  - Cyanobacterial blooms drive water-quality and aquatic-ecosystem deterioration in
      eutrophic lakes worldwide, mainly owing to their harmful, secondary metabolites.
      The response of fish exposed to these cyanobacterial chemicals, however, remains
      largely unknown. In this paper, we employed an endangered fish species
      (Sinocyclocheilus grahami) in Dianchi Lake, China to evaluate the risks of cell
      free exudates (MaE) produced by a dominant cyanobacterium (Microcystis
      aeruginosa) on embryo development, as well as the molecular mechanisms
      responsible. MaE (3d cultured) caused a reduction of fertilization (35.4%) and
      hatching (15.5%) rates, and increased mortality rates (<=90.0%) and malformation
      rate (27.6%), typically accompanied by heart failure. Proteomics analysis
      revealed that two greatest changed proteins - protein S100A1 (over-expressed 26
      times compared with control) and myosin light chain (under-expressed 25 fold) -
      are closely associated with heart function. Further study revealed that heart
      failure was due to calcium ion imbalance and malformed cardiac structure. We
      conclude that harmful secondary metabolites from cyanobacteria may adversely
      affect embryo development in this endangered fish, and possibly contribute to its
      disappearance and unsuccessful recovery in Dianchi Lake. Hazardous consequences
      of substances released by cyanobacteria should raise concerns for managers
      addressing recovery of this and other imperiled species in affected lakes.

PMID- 29169053
TI  - Titania/lignin hybrid materials as a novel support for alpha-amylase
      immobilization: A comprehensive study.
AB  - alpha-Amylase from Aspergillus oryzae was immobilized via covalent bonds and by
      physical interactions on a synthesized titania/lignin novel hybrid support. A
      temperature of 5 degrees C, a pH of 7.0, an initial enzyme solution concentration
      of 3.0mg/mL and a 3h process duration were found to be optimal for the highest
      activity of the immobilized enzyme. Moreover, the effect of temperature, pH,
      storage time and repeated catalytic cycles on the activity of free and
      immobilized enzyme was examined. Bound alpha-amylase showed enhanced thermal and
      chemical stability, and its reusability was also improved. Immobilized alpha
      amylase retained over 80% of its initial activity when stored for 30days at 4
      degrees C. Kinetic parameters of the free and immobilized biocatalyst were
      calculated and compared. The maximum reaction rate (Vmax) and turnover number
      (kcat) were slightly lower for the immobilized enzyme than for the free enzyme.
      It should be clearly stated that this work presents a useful protocol to produce
      stable and active immobilized alpha-amylase onto titania/lignin hybrid which may
      also be applied to immobilization of other enzymes.

PMID- 29169052
TI  - Estrogenic and anti-androgenic effects of the herbicide tebuthiuron in male Nile
      tilapia (Oreochromis niloticus).
AB  - Tebuthiuron is a phenylurea herbicide widely used in agriculture that can reach
      the aquatic environments, possibly posing negative effects to the aquatic biota.
      Phenylurea herbicides, such as diuron, are known to cause estrogenic and anti
      androgenic effects in fish, but no such effects were yet reported for tebuthiuron
      exposure. Thus, the aim of this study was to evaluate if tebuthiuron, at
      environmentally relevant concentrations (100 and 200ng/L) and after 25days of
      exposure have estrogenic and/or anti-androgenic effects on male of Nile tilapia
      (Oreochromis niloticus), through the evaluation of plasmatic testosterone (T) and
      estradiol (E2) levels, brain aromatase (CYP19) levels (western-blot), and by
      evaluating the histology of the testicles. When compared to the control group,
      plasmatic T levels decreased about 76% in the animals exposed to 200ng/L of
      tebuthiuron, while E2 levels increased about 94%, which could be related to a
      significant increase (77%) in CYP19A1 levels, an enzyme that catalyzes the
      conversion of androgens into estrogens. Histological analyses of the testicles
      also demonstrated that tebuthiuron at both tested concentrations caused a
      decrease in the diameter of the seminiferous tubules and in the diameter of the
      lumen. Therefore, the gonadosomatic index (GSI) was reduced by 36% % in the
      animals exposed 200ng/L to tebuthiuron. Indeed, the relative frequency of
      spermatocytes and spermatids increased respectively 73% (200ng/L) and 61%
      (100ng/L) in the tebuthiuron exposed animals, possibly due to the impairment of
      sperm release into the lumen, that was decreased 93% (200ng/L) in the treated
      animals compared to the control. These results confirm that tebuthiuron causes
      estrogenic and anti-androgenic effects in Nile tilapias at environmentally
      relevant concentrations.

PMID- 29169054
TI  - Reliability and validity of a Coda Motion 3-D Analysis system for measuring
      cervical range of motion in healthy subjects.
AB  - In the past two decades, many tools have been reported to measure the cervical
      range of motion (CROM), but most of the results are controversial in healthy
      individuals and/or individuals with neck pain. The Coda Motion 3-D Analysis
      system is a new instrument that measures three-dimensional joint movement.
      However, measurements of CROM using this system have yet to be conducted. Here,
      we investigate the reliability and validity of the Coda Motion 3-D Analysis
      System for measuring CROM in healthy adults. Sixty healthy volunteers were
      involved in this reliability study. Two trained investigators (M1 and M2) used
      the Coda Motion 3-D Analysis System to measure CROM. M1 and M2 measured all the
      volunteers once independently; after a short rest, M1 then measured all of them
      again. The intraclass correlation coefficient (ICC), standard error of the
      measurements (SEM), smallest detectable difference (SDD), a scatter diagram, and
      the limits of agreement (LoAs) were applied to evaluate the inter-tester and
      intra-tester reliability. Thirty healthy volunteers were involved in this
      validity study. The cervical flexion and extension ranges of motion were measured
      simultaneously with both the Coda Motion 3-D Analysis System and X-ray. A scatter
      diagram, the Pearson correlation coefficient and LoAs were used to evaluate the
      validity. Excellent intra-tester and inter-tester reliabilities were observed for
      the Coda Motion 3-D Analysis System (intra-tester ICC: 0.84-0.95, inter-tester
      ICC: 0.84-0.90). Good validity was achieved in extension and flexion with Pearson
      correlation coefficients ranging from 0.78 to 0.91. The Coda Motion 3-D Analysis
      System has excellent reliability for the measurement of CROM and good validity
      for measurements of flexion and extension in healthy subjects. This system has
      the potential to be used to measure the normal active CROM in the clinic and is
      accurate, safe, non-invasive, and radiation free.

PMID- 29169055
TI  - Functional electrical stimulation-induced muscular fatigue: Effect of fiber
      composition and stimulation frequency on rate of fatigue development.
AB  - This investigation evaluated the progression towards fatigue in two muscles of
      differing fast- and slow-twitch fiber proportions (abductor pollicis brevis (APB)
      and vastus lateralis (VL)) when activated by functional electrical stimulation
      (FES) at three frequencies (10, 35, and 50 Hz). Fatigue was defined as a 50% drop
      from the initial FES-induced force of 25% maximal voluntary contraction (MVC).
      Ten healthy adults (mean age: 23.2 +/- 3.0 years) were recruited; participants
      signed an IRB approved consent form prior to participation. Protocols were
      developed to evaluate the effects of muscle size, fiber type and FES frequency on
      total time to fatigue. Results indicated that the predominantly fast-twitch VL
      fatigued more quickly than the slow-twitch APB at the higher frequencies (p <
      0.05), but did not significantly differ with stimulation at 10 Hz. Overall,
      muscle size and FES frequencies showed some significant interactions when
      generating a defined force and during fatigue development. Furthermore, it
      appears that to reduce fatigue, FES treatments should not extend past ~14-16 min
      for large and small muscle groups, respectively, when the muscle group's optimal
      stimulation frequency is applied.

PMID- 29169056
TI  - Engineering microorganisms for improving polyhydroxyalkanoate biosynthesis.
AB  - Biosynthesis of polyhydroxyalkanoates (PHA) has been studied since the 1920s. The
      biosynthesis pathways have been well understood and various attempts have been
      made to improve the PHA biosynthesis efficiency. Recent progresses have been
      focused on systematic improvements on PHA biosynthesis including changing growth
      pattern for rapid proliferation, engineering to enlarge cell sizes for more PHA
      accumulation space, reprogramming the PHA synthesis pathways using optimized RBS
      and promoter, redirecting metabolic flux to PHA synthesis using CRISPR/Cas9
      tools, and very importantly, the employment of non-traditional host such as
      halophiles for reduced complexity on PHA production. All of the efforts should
      lead to ultrahigh PHA accumulation, controllable PHA compositions and molecular
      weights, open and continuous PHA production with gravity separation processes,
      resulting in competitive PHA production cost.

PMID- 29169057
TI  - Synthetic social support: Theorizing lay health worker interventions.
AB  - Levels of social support are strongly associated with health outcomes and
      inequalities. The use of lay health workers (LHWs) has been suggested by policy
      makers across the world as an intervention to identify risks to health and to
      promote health, particularly in disadvantaged communities. However, there have
      been few attempts to theorize the work undertaken by LHWs to understand how
      interventions work. In this article, the authors present the concept of
      'synthetic socialsupport' and distinguish it from the work of health
      professionals or the spontaneous social support received from friends and family.
      The authors provide new empirical data to illustrate the concept based on
      qualitative, observational research, using a novel shadowing method involving
      clinical and non-clinical researchers, on the everyday work of 'pregnancy
      outreach workers' (POWs) in Birmingham, UK. The service was being evaluated as
      part of a randomized controlled trial. These LHWs provided instrumental,
      informational, emotional and appraisal support to the women they worked with,
      which are all key components of social support. The social support was
      'synthetic' because it was distinct from the support embedded in spontaneous
      social networks: it was non-reciprocal; it was offered on a strictly time-limited
      basis; the LHWs were accountable for the relationship, and the social networks
      produced were targeted rather than spontaneous. The latter two qualities of this
      synthetic form of social support may have benefits over spontaneous networks by
      improving the opportunities for the cultivation of new relationships (both strong
      and weak ties) outside the women's existing spontaneous networks that can have a
      positive impact on them and by offering a reliable source of health information
      and support in a chaotic environment. The concept of SSS can help inform policy
      makers about how deploying lay workers may enable them to achieve desired
      outcomes, specify their programme theories and evaluate accordingly.

PMID- 29169058
TI  - Cyclic di-AMP in host-pathogen interactions.
AB  - Cyclic di-AMP (c-di-AMP) is a bacterial signaling nucleotide synthesized by
      several human pathogens. This widespread and specific bacterial product is
      recognized by infected host cells to trigger an innate immune response. Detection
      of c-di-AMP in the host cytosol leads primarily to the induction of type I
      interferon via the STING-cGAS signaling axis, while being also entangled in the
      activation of the NF-kappaB pathway. During their long-standing interaction, host
      and pathogens have co-evolved to control c-di-AMP activation of innate immunity.
      On the bacterial side, the quantity of c-di-AMP released inside cells allows to
      manipulate the host response to exacerbate infection by avoiding immune
      recognition or, at the opposite, by overloading the STING-cGAS pathway.

PMID- 29169059
TI  - Adsorption of ammonia molecules and humidity on germanane nanosheet-A density
      functional study.
AB  - The structural stability and electronic properties of pristine and Ga substituted
      germanane nanosheet were investigated using the density functional theory
      technique. The stability of bare and Ga substituted germanane nanosheet is
      substantiated with formation energy. The energy band gap opens upon hydrogenation
      on germanene sheet, which is utilized as a sensor material for the detection of
      NH3 and H2O molecules. The interaction of ammonia and humidity on germanane
      nanosheet is explored using the projected density of states, Bader charge
      transfer, adsorption energy, average energy gap variation, energy gap and
      electron density. The interaction of H2O and NH3 gas molecules on germanane
      material is studied in atomistic level. The interaction of humidity on pristine
      germanane nanosheet and NH3 on Ga substituted germanane nanosheet is found to be
      more favorable. The findings recommend that germanane nanosheet can be utilized
      as a chemi-resistor for the detection of humidity and trace levels of ammonia gas
      in the environment.

PMID- 29169060
TI  - Involuntary autobiographical memories are relatively more often reported during
      high cognitive load tasks.
AB  - Recent studies on involuntary autobiographical memories (IAMs) in daily life have
      shown that they are most frequently reported during daily routines (e.g. while
      ironing). Such studies have suggested that reporting IAMs may be influenced by
      the level of the ongoing task demands and availability of cognitive resources. In
      two studies, we investigated the effects of cognitive load on reporting IAMs. To
      examine the presumed cognitive load dependency of IAMs, we utilised an often
      employed experimental paradigm (Schlagman & Kvavilashvili, 2008) to elicit IAMs
      under conditions that differed in cognitive load. When performing a vigilance
      task, participants had to interrupt the task each time they experienced any
      spontaneous mental contents and write them down. We manipulated the level of
      cognitive load by either instructing (cognitive load group) or not instructing
      (control group) participants to perform an additional demanding task. We compared
      the groups on the number of IAMs and other mental contents (non-IAM contents)
      recorded, as well as on the frequency of IAMs that was calculated as a proportion
      of IAMs in all mental contents reported by the participant. We expected that if
      reporting IAMs depends on the level of cognitive demands, then we should observe
      lower frequency of IAMs in the cognitive load group compared to the control
      group. Consistently across studies, we observed a lower number of IAMs and non
      IAM contents in the cognitive load group. However, IAMs unexpectedly constituted
      a higher percentage of all mental contents when participants were cognitively
      loaded. Further implications of the cognitive load effects for IAMs research and
      experimental methodology are discussed.

PMID- 29169062
TI  - Study on a new design of Tehran Research Reactor for radionuclide production
      based on fast neutrons using MCNPX code.
AB  - The aim of this work is to increase the magnitude of the fast neutron flux inside
      the flux trap where radionuclides are produced. For this purpose, three new
      designs of the flux trap are proposed and the obtained fast and thermal neutron
      fluxes compared with each other. The first and second proposed designs were a
      sealed cube contained air and D2O, respectively. The results of calculated
      production yield all indicated the superiority of the latter by a factor of 55%
      in comparison to the first proposed design. The third proposed design was based
      on changing the surrounding of the sealed cube by locating two fuel plates near
      that. In this case, the production yield increased up to 70%.

PMID- 29169061
TI  - Measurement of cross-sections for 14MeV neutron interaction with 175Lu.
AB  - The cross-sections for 14MeV neutron interaction with 175Lu were precisely
      measured by the neutron activation and off-line gamma ray technique. The neutron
      fluence was monitored by the accompanying alpha-particle of the T(d,n)alpha
      reaction, and the neutron energies were determined by using the cross-section
      ratio method of 90Zr(n,2n)89Zr to 93Nb(n,2n)92mNb reactions. As a result, the
      cross-sections of 175Lu(n,2n)174mLu, 175Lu(n,2n)174gLu, 175Lu(n,p)175m+gYb and
      175Lu(n,alpha)172Tm reactions have been deduced at En = 14.1 +/- 0.3MeV, 14.5 +/-
      0.3MeV and 14.7 +/- 0.3MeV, respectively. Meanwhile, the comparisons between this
      work and the date reported by other groups previously were also given. For the
      comparison, it was found that there were nonnegligible discrepancies among these
      experimental data, as well as for several databases. As a conclusion, present
      data seem to be more consistent with the database of ENDF/B-VII.1, but trend to
      be lower than those of JEFF-3.2 and FENDL-3.1b, except the 175Lu(n,2n)174m+gLu
      reaction which are all in agreement.

PMID- 29169063
TI  - Measurement of absolute gamma-ray emission probabilities in the decay of 235U.
AB  - Accurate measurements were performed of the photon emission probabilities
      following the alpha decay of 235U to 231Th. Sources of highly enriched 235U were
      characterised in terms of isotopic composition by mass spectrometry and their
      activities were standardised by means of alpha-particle counting at a low defined
      solid angle. The standardised sources were subsequently measured by high
      resolution gamma-ray spectrometry with calibrated high-purity germanium detectors
      to determine the photon emission probabilities. Four laboratories participated in
      this work and reported emission probabilities for 33 gamma-ray lines. Most of
      them agree with previously published evaluated data. In addition, new values are
      proposed for gamma-lines which have been measured only once in the past.

PMID- 29169064
TI  - Eukaryotic initiation factor 4F-sidestepping resistance mechanisms arising from
      expression heterogeneity.
AB  - There is enormous diversity in the genetic makeup and gene expression profiles
      between and within tumors. This heterogeneity leads to phenotypic variation and
      is a major mechanism of resistance to molecular targeted therapies. Here we
      describe a conceptual framework for targeting eukaryotic initiation factor (eIF)
      4F in cancer-an essential complex that drives and promotes multiple Cancer
      Hallmarks. The unique nature of eIF4F and its druggability bypasses several of
      the heterogeneity issues that plague molecular targeted drugs developed for
      cancer therapy.

PMID- 29169065
TI  - Can postmortem proteolysis explain tenderness differences in various bovine
      muscles?
AB  - This study investigated the relationship between postmortem proteolysis, muscle
      pH decline, sarcomere length (SL), intramuscular fat (IMF) and Warner-Bratzler
      shear force (WBSF) in four bovine muscles (biceps femoris (BF), infraspinatus
      (IS), longissimus lumborum (LL), psoas major (PM). The WBSF was low in BF, IS and
      PM, while LL had a higher value (P<0.001), but still considered as tender. The PM
      had fastest pH decline (P<0.001), ultimate pH was lowest in LL and PM and highest
      for IS (P<0.001), sarcomeres were longest for PM and shortest for BF and LL
      (P<0.001), while IS and PM had more IMF than BF and LL (P=0.038). Troponin T
      degradation was similar in all muscles after 2d postmortem, however after 13d LL
      had more degradation than IS (P=0.003). The MMP-2 activity increased during
      storage (P=0.001), while IS had less activity than the other muscles (P=0.022).
      Although the variation in proteolytic activity could not explain the variation in
      WBSF, the study provides useful knowledge for the meat industry for optimising
      processing and storage procedures for different beef muscles.

PMID- 29169066
TI  - Shining a light on enzyme promiscuity.
AB  - Most, if not all, enzymes are capable of catalyzing physiologically irrelevant
      secondary reactions-termed 'promiscuous' reactions-in addition to the reactions
      that they have evolved to catalyze. Promiscuous activities can provide the
      starting point for evolution of new enzymes, both in nature and in the hands of
      protein engineers. Recent work suggests that the universe of promiscuous
      activities available in nature is enormous. New high-throughput approaches have
      significantly advanced our ability to identify promiscuous activities, setting
      the stage for synthetic biology efforts to construct novel pathways using
      catalysts derived from promiscuous enzymes via directed evolution.

PMID- 29169067
TI  - The role of personal resilience and personality traits of healthcare students on
      their attitudes towards interprofessional collaboration.
AB  - BACKGROUND: Interprofessional collaboration (IPC) improves communication between
      healthcare workers and healthcare delivery. Interprofessional education (IPE) is
      essential in preparing healthcare students for cooperating with other healthcare
      disciplines in a real work setting. Although higher education settings have a
      responsibility to provide collaborative healthcare practice to students, IPE has
      not yet been prompted worldwide as a formal division in health professional
      education and in Israel IPE among health professions students is scarce.
      OBJECTIVE: To examine the attitudes of health professions students towards IPC in
      correlation with their personal resilience and personality traits. DESIGN: A
      descriptive cross-sectional design was used. SETTING AND PARTICIPANTS:
      Participants were fourth year nursing, occupational therapy (OT), and physical
      therapy students studying in an academic undergraduate program at a School of
      Health Professions in a central university in Israel. METHODS: Attitudes were
      assessed with a questionnaire consisting of the Interdisciplinary Education
      Perception Scale, the Connor-Davidson Resilience Scale, the Big Five Inventory of
      personality dimensions, and a question evaluating students' experience with the
      PBL (Problem-Based Learning) method. RESULTS: Questionnaires were completed by
      184 health professions students. Nursing students' perception of actual
      cooperation with other professions and their perceived competency and autonomy in
      their profession were slightly lower than those of other students. Among nursing
      students, positive correlations were found between competency & autonomy and
      resilience (p<0.01) and between competency & autonomy and agreeableness (p<0.05).
      Positive correlations were also found between their perception of actual
      cooperation with other professions and: resilience (p<0.01), agreeableness
      (p<0.05), conscientiousness (p<0.05), and openness (p<0.05). Only OT students
      were familiar with and experienced in the PBL method. This experience with PBL
      was found correlated with more positive attitudes towards competency and autonomy
      in the profession and higher positive perception of actual cooperation with other
      professions. CONCLUSIONS: IPE, including PBL, should be integrated in health
      professions students' training.

PMID- 29169069
TI  - Anti-inflammatory agents in peripheral arterial disease.
AB  - Inflammation is pivotally involved in coronary and peripheral atherosclerotic
      disease. This established concept is based on both experimental animal models of
      vascular inflammation and Mendelian randomization studies demonstrating a causal
      relationship between pro-inflammatory cytokines (e.g. interleukin-6) and
      cardiovascular disease risk. More recently, the reduction of cardiovascular
      events by use of an interleukin-1beta inhibitor (canakinumab) has revived
      interest in the use of anti-inflammatory agents for the treatment of
      atherosclerotic disease, including peripheral arterial disease. In this mini
      review article we provide an update on the pleiotropic anti-inflammatory
      properties of approved drugs for use in cardiovascular disease (e.g.
      antiplatelets, statins, PCSK9 inhibitors) and discuss the role of targeted or
      untargeted anti-inflammatory atheroprotection in peripheral arterial disease by
      agents such as colchicine, methotrexate, anti-TNF-alpha agents and monoclonal
      antibodies against interleukin-signaling.

PMID- 29169068
TI  - Effects of a service learning experience on confidence and clinical skills in
      baccalaureate nursing students.
AB  - BACKGROUND: Camp programs yield positive and lasting benefits for children.
      Integrating a summer camp into a nurse course with a service learning design
      fosters learning beyond the classroom and enhances community engagement.
      OBJECTIVE: The purpose of this study is to describe the nursing students'
      experience and perceived confidence after completing a service learning nursing
      course. DESIGN: This is a descriptive, qualitative research study that used
      reflection and a perceived confidence questionnaire. SETTING: The study was
      conducted in a school of nursing and surrounding university campus facilities
      during the diabetes camp. PARTICIPANTS: The participants (n=23) were nursing
      students who enrolled in the nursing course. METHODS: As part of the course
      requirements, students completed an eight item question confidence survey before
      and after the diabetes camp related to diabetes and camp management, and
      interpersonal abilities with patients, families, and healthcare professionals.
      Within 48-72h after diabetes camp, the students completed the reflection paper.
      The pre and post Confidence Surveys were analyzed using a t-test and thematic
      analysis was used to analyze the reflection paper. RESULTS: Overall, perceived
      confidence levels increased after completing the service learning course (t=
      9.91, p=0.001). Four themes emerged from the qualitative analysis: pre-camp
      assumptions and fears, growth in confidence, understanding diabetes management in
      the community, and appreciation for learning beyond the classroom and hospital
      setting. CONCLUSIONS: This service learning course provided nursing students the
      ability to not only develop diabetes clinical skills and perceived confidence,
      but also life skills including teamwork, leadership, and conflict resolution.

PMID- 29169070
TI  - Optimal blood pressure level and acute kidney injury after gastrointestinal
      surgery.

PMID- 29169071
TI  - Psychosocial interventions in breast cancer survivorship care.
AB  - Cancer distress screening and subsequent referral for psychosocial intervention
      has been mandated for continued cancer center accreditation. Increasing emphasis
      is being placed on the referral component of this mandate, ensuring that patient
      distress is not only identified but also effectively treated. Many evidence-based
      interventions exist for cancer distress. Specific interventions can effectively
      target biopsychosocial impacts of stress and promote adaptive coping, focusing on
      problem-solving, social support utilization, assertive communication, sexual
      health and intimacy, adherence to medical and supportive care recommendations,
      health behavior change, and emotional processing and expression. In randomized
      clinical trials, specific interventions have also been associated with biological
      improvements, including neuroendocrine and immune functioning, decreased rates of
      breast cancer recurrence, and improved survival rates. As cancer treatments
      advance and patients live longer, it is pertinent to treat the impacts of breast
      cancer with evidence-based interventions.

PMID- 29169072
TI  - Genomics of foodborne pathogens for microbial food safety.
AB  - Whole genome sequencing (WGS) has been broadly used to provide detailed
      characterization of foodborne pathogens. These genomes for diverse species
      including Salmonella, Escherichia coli, Listeria, Campylobacter and Vibrio have
      provided great insight into the genetic make-up of these pathogens. Numerous
      government agencies, industry and academia have developed new applications in
      food safety using WGS approaches such as outbreak detection and characterization,
      source tracking, determining the root cause of a contamination event, profiling
      of virulence and pathogenicity attributes, antimicrobial resistance monitoring,
      quality assurance for microbiology testing, as well as many others. The future
      looks bright for additional applications that come with the new technologies and
      tools in genomics and metagenomics.

PMID- 29169073
TI  - Difficulty of confining recalcitrant tuberculosis patients in isolation wards in
      Japan, 2013-2014.
AB  - OBJECTIVES: In Japan, approximately 7000 smear-positive tuberculosis (TB) cases
      were reported in 2014. According to the law, such patients must be isolated in a
      TB ward until they become at least sputum smear-negative. However, there are some
      recalcitrant patients who are difficult to isolate because of problematic
      behaviors. This study was conducted to characterize recalcitrant TB patients and
      determine why they left the hospitals and how they were followed up after they
      left. STUDY DESIGN: Cross-sectional study. METHODS: We sent a self-administered
      questionnaire to the hospitals in Japan with over 11 TB isolation beds, asking
      about recalcitrant TB inpatients from April 2013 through March 2014, in terms of
      demographic information, the reasons why they left, and how they were followed
      up. RESULTS: A total of 38 recalcitrant patients were reported, of whom 15
      (39.5%) self-discharged, eight (21.0%) were discharged, and 15 (39.5%) were
      transferred. Thirty-three (86.8%) were males. The main reason (52.6%) why the
      patients were considered recalcitrant was related to psychiatric problems.
      However, nine (23.6%) patients physically assaulted or insulted the staff
      members. Thirty-six (94.7%) were able to continue anti-TB treatment after they
      left the original hospital. CONCLUSION: Although the number of recalcitrant TB
      patients who were abusive was small, there should be TB facilities with law
      enforcement officials readily available to enforce isolation.

PMID- 29169074
TI  - Flow stagnation volume and abdominal aortic aneurysm growth: Insights from
      patient-specific computational flow dynamics of Lagrangian-coherent structures.
AB  - Abdominal aortic aneurysms (AAA) are localized, commonly-occurring dilations of
      the aorta. When equilibrium between blood pressure (loading) and wall mechanical
      resistance is lost, rupture ensues, and patient death follows, if not treated
      immediately. Experimental and numerical analyses of flow patterns in arteries
      show direct correlations between wall shear stress and wall mechano-adaptation
      with the development of zones prone to thrombus formation. For further insights
      into AAA flow topology/growth interaction, a workout of patient-specific
      computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov
      exponents and extract Lagrangian-coherent structures (LCS). This computational
      model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI)
      in 5 patients. To better understand the impact of flow topology and transport on
      AAA growth, hyperbolic, repelling LCS were computed in 1 patient during 8-year
      follow-up, including 9 volumetric morphologic AAA measures by computed tomography
      angiography (CTA). LCS defined barriers to Lagrangian jet cores entering AAA.
      Domains enclosed between LCS and the aortic wall were considered to be stagnation
      zones. Their evolution was studied during AAA growth. Good correlation - 2-D
      cross-correlation coefficients of 0.65, 0.86 and 0.082 (min, max, SD) - was
      obtained between numerical simulations and 4-D MRI acquisitions in 6 specific
      cross-sections from 4 patients. In follow-up study, LCS divided AAA lumens into 3
      dynamically-isolated zones: 2 stagnation volumes lying in dilated portions of the
      AAA, and circulating volume connecting the inlet to the outlet. The volume of
      each zone was tracked over time. Although circulating volume remained unchanged
      during 8-year follow-up, the AAA lumen and main stagnation zones grew
      significantly (8 cm3/year and 6 cm3/year, respectively). This study reveals that
      transient transport topology can be quantified in patient-specific AAA during
      disease progression by CTA, in parallel with lumen morphology. It is anticipated
      that analysis of the main AAA stagnation zones by patient-specific CFD on a
      yearly basis could help to predict AAA growth and rupture.

PMID- 29169075
TI  - Maternal intention to exclusively breast feed among mainland Chinese mothers: A
      cross-sectional study.
AB  - OBJECTIVE: to examine postpartum maternal recall of their intentions to
      exclusively breast feed among breastfeeding women and identify its predictors.
      DESIGN AND SETTING: a cross-sectional descriptive study was conducted in a
      regional teaching hospital at Guangzhou, China between April 1 and July 14, 2014.
      PARTICIPANTS: 571 mothers who were within four days after delivery were recruited
      to the study. MEASUREMENTS: data were collected by four research assistants with
      maternal intention to breast feed data sheet, the Network Support for
      Breastfeeding Scale (NSBS), and a socio-demographic data sheet. FINDINGS: greater
      than half of the mothers (69.5%) intended to exclusively breast feed. The
      logistic regression analysis revealed six variables which predicted postpartum
      maternal recall of their intentions to exclusively breast feed. They were support
      from husband, being breast-fed as an infant, previous breast feeding experience,
      attending antenatal breast feeding class, time of decision to breast feed, and
      the rating of the importance of my baby's health. CONCLUSION AND IMPLICATIONS FOR
      PRACTICE: health care professionals could develop strategies to enhance mothers'
      intention to exclusively breast feed, such as providing antenatal breast feeding
      class on internet, a strong focus on the benefits of exclusive breast feeding on
      the baby's health in the education programme, and more efforts directed toward
      educating school-aged children and adolescents to modify societal perceptions of
      what are considered normal infant feeding. Mothers' husband could be encouraged
      in supporting exclusive breast feeding.

PMID- 29169076
TI  - Corrigendum to "Two goitrogenic 1,3-oxazolidine-2-thione derivatives from
      Brassicales taxa: Challenging identification, occurrence and immunomodulatory
      effects" [Food Chem. Toxicol. (2017) 94-108].

PMID- 29169077
TI  - Quantifying the exposure of humans and the environment to oil pollution in the
      Niger Delta using advanced geostatistical techniques.
AB  - The Niger Delta is one of the largest oil producing regions of the world. Large
      numbers and volumes of oil spills have been reported in this region. What has not
      been quantified is the putative exposure of humans and/or the environment to this
      hydrocarbon pollution. In this novel study, advanced geostatistical techniques
      were applied to an extensive database of oil spill incidents from 2007 to 2015.
      The aims were to (i) identify and analyse spill hotspots along the oil pipeline
      network and (ii) estimate the exposure of the hydrocarbon pollution to the human
      population and the environment within the Niger Delta. Over the study period
      almost 90millionlitres of oil were released. Approximately 29% of the human
      population living in proximity to the pipeline network has been potentially
      exposed to oil contamination, of which 565,000 people live within high or very
      high spill intensity sectors. Over 1000km2 of land has been contaminated by oil
      pollution, with broadleaved forest, mangroves and agricultural land the most
      heavily impacted land cover types. Proximity to the coast, roads and cities are
      the strongest spatial factors contributing to spill occurrence, which largely
      determine the accessibility of sites for pipeline sabotage and oil theft.
      Overall, the findings demonstrate the high levels of environmental and human
      exposure to hydrocarbon pollutants in the Niger Delta. These results provide
      evidence with which to spatially target interventions to reduce future spill
      incidents and mitigate the impacts of previous spills on human communities and
      ecosystem health.

PMID- 29169078
TI  - Amino acids/peptides conjugated heterocycles: A tool for the recent development
      of novel therapeutic agents.
AB  - Amino acids/peptide conjugated heterocycles represent an important class of
      therapeutical agents. Biologically active heterocycles are conjugated with amino
      acids or peptides to increase the drug resistance. Furthermore, the amino
      acid/peptide based drugs have low toxicity, ample bioavailability and
      permeability, modest potency and good metabolic and pharmacokinetic properties.
      Synthetic amino acid/peptides based heterocyclic conjugates constitute a
      promising choice for the development of new, less toxic and safer conventional
      pharmaceutical drugs in the near future. In this review, we discuss and highlight
      the recent findings of the structural features that encourage biological
      applications of amino acid/peptides based conjugates.

PMID- 29169079
TI  - Design, synthesis and molecular docking of thiazolidinedione based benzene
      sulphonamide derivatives containing pyrazole core as potential anti-diabetic
      agents.
AB  - We herein report the design, synthesis and molecular docking studies of 2,4
      thiazolidinedione derivatives containing benzene sulphonyl group which are docked
      against the Peroxisome Proliferator Activated Receptor (PPARgamma) target.
      Compound 7p was most effective in lowering the blood glucose level as compared to
      standard drugs pioglitazone and rosiglitazone. Compound 7p exhibited potent PPAR
      gamma transactivation of 61.2% with 1.9 folds increase in gene expression. In
      molecular docking studies 7p showed excellent interactions with amino acids TYR
      473, SER 289, HIE 449, TYR 327, ARG 288, MET 329 and LEU 228. Compound 7p did not
      cause any damage to the liver without any noteworthy weight gain and may be
      considered as promising candidates for the development of new antidiabetic
      agents.

PMID- 29169080
TI  - Novel and rare prenyllipids - Occurrence and biological activity.
AB  - The data presented indicate that there is a variety of unique prenyllipids, often
      of very limited taxonomic distribution, whose origin, biosynthesis, metabolism
      and biological function deserves to be elucidated. These compounds include
      tocoenols, tocochromanol esters, tocochromanol acids, plastoquinones and
      ubiquinones. Additionally, based on the available data, it can be assumed that
      there are still unrecognized prenyllipids, like prenylquinols fatty acid esters
      of the hydroquinone ring, including prenylquinol phosphates, and others, whose
      biological function might be of great importance. Our knowledge of these
      compounds is not only important from the scientific point of view, but may also
      be of practical significance to medicine, pharmacy or cosmetics.

PMID- 29169081
TI  - Transcriptome profiling reveals specific patterns of paclitaxel synthesis in a
      new Taxus yunnanensis cultivar.
AB  - The difference in contents of paclitaxel and 10-deacetylbaccatin III (10-DABIII)
      in needles between wildtype (WT) and a new cultivar (Zhongdayihao, ZD1) of Taxus
      yunnanensis was examined. Transcriptome profiling was conducted for different
      tissues of the ZD1 and WT to illustrate the regulation mechanism of paclitaxel
      biosynthesis. It was observed that average contents of paclitaxel and 10-DABIII
      in ZD1 were 4 folds and 32 folds higher than those in WT, respectively. More
      significant elevations of differential expressed genes (DEGs) from paclitaxel
      biosynthesis pathway were revealed in ZD1 rather than WT, which should be
      responsible for the higher contents of paclitaxel and 10-DABIII in the ZD1.
      Special tissues-dependent expression patterns of paclitaxel biosynthesis DEGs in
      ZD1 compared to WT were unraveled. The relative higher expressions of paclitaxel
      biosynthesis genes in needles than other tissues supported the higher content of
      paclitaxel and 10-DABIII content in needles of ZD1. Attenuation of plant hormone
      signal transduction pathway led to the lower expression of TFs in ZD1 rather than
      WT. Besides, the significant negative correlations between differential expressed
      TFs and DEGs from paclitaxel biosynthesis pathway displayed a possibly negative
      regulation pattern of these TFs on paclitaxel biosynthesis pathway genes. These
      results provided new insights into the molecular process of paclitaxel synthesis
      in Taxus.

PMID- 29169083
TI  - Political aspects of shared reality.
AB  - The political world permeates people's everyday experiences. In this article, we
      review recent research concerning how the pursuit, creation, and maintenance of
      shared reality underlie important political phenomena. We address three general
      points. First, we discuss how the desire to share reality shapes the political
      attitudes that people adopt. Second, we outline how the existence of competing
      representations of reality can lead to prolonged political conflicts that are
      challenging to overcome. Third, we consider how and why shared reality
      contributes to social stasis and change. A scientifically informed understanding
      of how shared reality shapes the political arena will enrich psychological
      research and facilitate addressing social issues.

PMID- 29169082
TI  - The safety and efficacy of propofol as a replacement for amobarbital in
      intracarotid Wada testing of presurgical patients with epilepsy.
AB  - OBJECTIVE: The intracarotid sodium amytal procedure (the "Wada test") has for
      many years been the gold standard for language and memory lateralization and
      remains an important part of presurgical analysis for patients with medically
      intractable seizures. Due to shortages in the key sedative (amobarbital),
      neuropsychologists have turned to alternatives such as propofol. Our aim was to
      investigate the safety and efficacy of propofol relative to amobarbital in the
      Wada test. METHODS: We performed a retrospective review of the 97 Wada procedures
      performed at University of Iowa Hospitals and Clinics from 2007 through mid-2015.
      RESULTS: Propofol produced similar lateralization rates as amobarbital for both
      language and memory. Similar rates of patients in each group went on to have the
      resection surgery. With regard to safety, there were no differences found in
      average rate or severity of adverse effects. None of the demographic
      characteristics reviewed were predictive of increased risk for either drug.
      SIGNIFICANCE: These findings support previous studies indicating that propofol is
      as safe and efficacious as amobarbital, and can continue to be used in Wada
      procedures with confidence.

PMID- 29169084
TI  - Changes in first trimester fetal CYP1A1 and AHRR DNA methylation and mRNA
      expression in response to exposure to maternal cigarette smoking.
AB  - Prenatal exposure to maternal cigarette smoking increases the risk of
      intrauterine growth retardation, adverse pregnancy outcomes, and diseases later
      in life. Exposure can result in postnatal global and gene-specific DNA
      methylation changes, with the latter well documented for the CYP1A1 and AHRR
      genes involved in the detoxification of xenobiotic substances. This study
      assessed the impact of exposure to maternal smoking on first trimester fetal
      CYP1A1 and AHRR mRNA expression and DNA methylation for CpG-sites displaying
      maternal smoking during pregnancy-mediated methylation changes at birth. The
      analyses included first trimester (6-12 weeks) placentas (N=39) and livers
      (N=43). For AHRR, exposure to maternal smoking was associated with increased DNA
      methylation in the placentas of female fetuses; mRNA expression, however, was
      unchanged. While exposure to maternal smoking was not associated with AHRR DNA
      methylation changes in fetal livers; mRNA expression was increased. For CYP1A1,
      exposure to maternal smoking was not associated with fetal DNA methylation
      changes whereas mRNA expression increased in placentas and male fetal livers.
      These results show that first trimester exposure to maternal smoking is
      associated with CYP1A1 and AHRR DNA methylation and mRNA expression changes.
      However, the results also indicate that maternal smoking during pregnancy
      mediated postnatal CYP1A1 and AHRR DNA methylation changes are not imprinted
      during the first trimester.

PMID- 29169085
TI  - Combined toxicity of triclosan, 2,4-dichlorophenol and 2,4,6-trichlorophenol to
      zebrafish (Danio rerio).
AB  - Triclosan (TCS), 2,4,6-trichlorophenol (2,4,6-TCP) and 2,4-dichlorophenol (2,4
      DCP) are the most prevalent chlorinated phenolic pollutants in aquatic
      environments. Our results showed LC50 and EC50 values of 0.51, 1.11, 2.45mg/L,
      and 0.36, 0.74, 1.53mg/L for TCS, 2,4,6-TCP and 2,4-DCP, respectively, to 120hpf
      zebrafish. The highest TCSD (the mixture of TCS, 2,4,6-TCP and 2,4-DCP) toxicity
      was observed at a TCS:2,4,6-TCP:2,4-DCP concentration ratio of 1:2:4. LC50 and
      EC50 values of TCSD mixtures for 120-hpf zebrafish were 2.28 and 1.16mg/L,
      respectively. Two toxicity assessment methods (Toxic Unit and Mixture Toxicity
      Index) indicated that TCSD interactions produced partly additive toxicity. TCSD
      exposure decreased zebrafish hatching rate and led to a series of malformations.
      Following alkaline phosphatase staining, a large area of vascular ablation was
      observed with almost complete disappearance of vascular branches and a smaller
      coverage range. Prominent reddening of the yolk sac and visceral mass after oil
      red O staining implied that TCSD exposure severely affected fat metabolism.
      Following acridine orange staining, cell death occurred in eyes while high TCSD
      concentrations (0.84mg/L) induced cardiovascular circulation dysfunction. Alcian
      blue staining increased the alpha angle between Meckel's cartilages and beta
      angle between two ceratobranchial. Basihyal and palatoquadrate became shorter and
      developmental abnormality or defects occurred in the fifth ceratobranchial.
      Overall, these results provide a theoretical basis for systematically evaluating
      the combined toxicity of the prevalent chlorinated phenolic pollutants in real
      world aquatic environments.

PMID- 29169086
TI  - Linking dynamic patterns of neural activity in orbitofrontal cortex with decision
      making.
AB  - Humans and animals demonstrate extraordinary flexibility in choice behavior,
      particularly when deciding based on subjective preferences. We evaluate options
      on different scales, deliberate, and often change our minds. Little is known
      about the neural mechanisms that underlie these dynamic aspects of decision
      making, although neural activity in orbitofrontal cortex (OFC) likely plays a
      central role. Recent evidence from studies in macaques shows that attention
      modulates value responses in OFC, and that ensembles of OFC neurons dynamically
      signal different options during choices. When contexts change, these ensembles
      flexibly remap to encode the new task. Determining how these dynamic patterns
      emerge and relate to choices will inform models of decision-making and OFC
      function.

PMID- 29169087
TI  - Antimicrobial discovery inspired by ecological interactions.
AB  - Bacteria represent an unparalleled source of antibiotics used to treat infectious
      diseases. Yet, genome analyses have revealed that their full biosynthetic
      potential is much larger than expected. Valuable strategies to unearth hidden
      antibiotics are genome mining, pathway engineering and triggering, as well as co
      cultivation approaches. Nevertheless, there is growing understanding that it is
      often essential to consider the ecological context and that there is a great
      potential for antimicrobial discovery from bacteria engaged in well-defined
      interactions with other organisms. Various ecological scenarios involving
      antimicrobial agents are outlined in this review: predator-prey and pathogenic
      interactions, the protection of insect assets such as offspring and cultivars, as
      well as host protection in symbiotic relationships with plants, invertebrates and
      animals/humans. The illustrative examples given reinforce the idea that
      examination of interactions between organisms can yield new antimicrobial
      compounds, and ultimately further our understanding of the function of these
      molecules in the environment.

PMID- 29169088
TI  - Systematically investigating the impact of medication on the gut microbiome.
AB  - In the recent years, there is accumulating evidence for a strong impact of
      medication on the gut microbiota composition. This evidence comes from
      metagenomics-based associations and extends beyond classical antibacterials to a
      handful of human-targeted drugs. To answer whether such effects are direct and
      explore their consequences in human health, we need to develop experimental
      platforms that will allow for systematic profiling of drug-microbiota
      interactions. Here, we discuss approaches, considerations, experimental setups
      and strategies that can be used to tackle this need, but can be also readily
      transmitted to related questions in the microbiome field. A comprehensive
      understanding of how therapeutics interact with gut microbes will open up the
      path for further mechanistic dissection of such interactions, and ultimately
      improve not only our understanding of the gut microbiome, but also drug safety
      and efficacy.

PMID- 29169089
TI  - Effect of organic loading rate on anaerobic co-digestion of rice straw and pig
      manure with or without biological pretreatment.
AB  - In this study, rice straw (RS) and pig manure (PM) mixtures with or without bio
      pretreatment were used as the substrates and digested in a 9 L of anaerobic
      reactor at Organic loading rates (OLRs) of 0.4-3.1 kg COD/(m3 d). The volumetric
      methane production rate (VMPR), methane yield and anaerobic stability were
      comparatively investigated. The results showed the co-anaerobic digestion
      processes of RS and PM mixture after biological pretreatment were very stable at
      OLRs of 0.4-2.5 kg COD/(m3 d), and its optimal VMPR and methane yield could reach
      0.64 L CH4/(L d) and 0.4557 L CH4/g CODremoved at OLR of 2.5 kg COD/(m3 d), which
      were 62.4% and 37.8% higher than those of the control under the same OLR
      condition. This study indicated the biological pretreatment with a cellulolytic
      microbial consortium own great potential in improving the methane yield and
      productivity of RS and PM wastes.

PMID- 29169090
TI  - Optimization of Fe2+ supplement in anaerobic digestion accounting for the Fe
      bioavailability.
AB  - Fe is widely used as an additive in anaerobic digestion, but its bioavailability
      and the mechanism by which it enhances digestion are unclear. In this study,
      sequential extraction was used to measure Fe bioavailability, while biochemical
      parameters, kinetics model and Q-PCR (fluorescence quantitative PCR) were used to
      explore its mechanism of stimulation. The results showed that sequential
      extraction is a suitable method to assess the anaerobic system bioavailability of
      Fe, which is low and fluctuates to a limited extent (1.7 to -3.1wt%), indicating
      that it would be easy for Fe levels to be insufficient. Methane yield increased
      when the added Fe2+ was 10-500mg/L. Appropriate amounts of Fe2+ accelerated the
      decomposition of rice straw and facilitated methanogen metabolism, thereby
      improving reactor performance. The modified Gompertz model better fitted the
      results than the first-order kinetic model. Feasibility analysis showed that
      addition of Fe2+ at <=50mg/L was suitable.

PMID- 29169091
TI  - Effects of sulphur on the performance of an anaerobic membrane bioreactor:
      Biological stability, trace organic contaminant removal, and membrane fouling.
AB  - This study investigated the impact of sulphur content on the performance of an
      anaerobic membrane bioreactor (AnMBR) with an emphasis on the biological
      stability, contaminant removal, and membrane fouling. Removal of 38 trace organic
      contaminants (TrOCs) that are ubiquitously present in municipal wastewater by
      AnMBR was evaluated. Results show that basic biological performance of AnMBR
      regarding biomass growth and the removal of chemical oxygen demand (COD) was not
      affected by sulphur addition when the influent COD/SO42- ratio was maintained
      higher than 10. Nevertheless, the content of hydrogen sulphate in the produced
      biogas increased significantly and membrane fouling was exacerbated with sulphur
      addition. Moreover, the increase in sulphur content considerably affected the
      removal of some hydrophilic TrOCs and their residuals in the sludge phase during
      AnMBR operation. By contrast, no significant impact on the removal of hydrophobic
      TrOCs was noted with sulphur addition to AnMBR.

PMID- 29169092
TI  - Triterpenoids with antiplatelet aggregation activity from Ilex rotunda.
AB  - Phytochemical studies on the barks of Ilex rotunda Thunb. had resulted in the
      isolation of seven previously undescribed triterpenoids, rotundinosides E-K,
      along with sixteen known ones. The structures of previously undescribed compounds
      were elucidated on the basis of extensive spectroscopic analysis and the sugar
      moieties were further identified by HPLC and GC after acid hydrolysis. Among the
      isolates, rotundinoside F featured a rare triterpene-phenylpropanoid hybrid
      structure and rotundinoside H was an uncommon triterpene saponin with alpha
      linked glucopyranosyl moiety at C-3. The antiplatelet aggregation of all
      compounds were evaluated against ADP induced rat platelet aggregation in vitro,
      and five compounds exhibited moderate inhibitory effects with IC50 values ranging
      from 22.4 to 32.8 MUM.

PMID- 29169093
TI  - The removal of fluoride from aqueous solution by a lateritic soil adsorption:
      Kinetic and equilibrium studies.
AB  - The use of natural sorbents to remove fluoride from drinking water is a promising
      alternative because of its low-cost and easy implementation. In this article,
      fluoride adsorption on a latosol soil from Misiones province (Argentina) was
      studied regarding kinetic and equilibrium aspects. Experiments were conducted in
      batch at room temperature under controlled conditions of pH 4-8) and ionic
      strength (1-10mM KNO3). Experimental data indicated that adsorption processes
      followed a PSO kinetic where initial rates have showed to be influenced by pH
      solution. The necessary time to reach an equilibrium state had resulted
      approximately 30min. Equilibrium adsorption studies were performed at pH 8 which
      is similar to the natural groundwater. For that, fluoride adsorption data were
      successfully adjusted to Dubinin-Ataskhov model determining that the fluoride
      adsorption onto soil particles mainly followed a physical mechanism with a
      removal capacity of 0.48mgg-1. Finally, a natural groundwater was tested with
      laterite obtaining a reduction close to 30% from initial concentration and
      without changing significantly the physicochemical properties of the natural
      water. Therefore, it was concluded that the use of lateritic soils for fluoride
      removal is very promising on a domestic scale.

PMID- 29169094
TI  - Evaluation of full pelvic ring stresses using a bilateral static gait-phase
      finite element modeling method.
AB  - Trauma to the pelvis is debilitating and often needs fixation intervention. In
      58% of patients with this trauma, the injuries can lead to permanent disability,
      preventing the return to jobs. Of all unsuccessful fixation procedures, 42% are
      caused by failures of the method, sometimes due to mobilization during healing.
      Patients would benefit by havibridgetv@comcast.netng fixation hardware in place
      that enabled ambulation. During walking the bilateral hip joint plus leg and
      trunk muscle forces, including those from hip motion, can induce torsion into the
      pelvic ring and across the joint cartilages, and affect the internal stresses of
      the pelvis. For an accurate understanding, fixation that bridges the bilateral
      innominate bones needs to be evaluated considering all of these factors, and the
      affect on the stresses throughout the pelvic ring. Yet there is no bilateral,
      comprehensive method to do so in the literature. In this study a method was
      developed that incorporates all of the necessary factors in four bilateral,
      static, finite element models representing eight gait phases. The resulting
      stress migration through the full pelvic ring and pubic symphysis displacements
      were demonstrated under these conditions. In subsequent work, fixation
      improvements can be applied to these models to evaluate the change in internal
      stresses, joint displacements and deformations of the hardware, leading to a
      better quality of design and permitting ambulation during healing for the
      patient.

PMID- 29169095
TI  - Bioactivity and properties of an adhesive system functionalized with an
      experimental niobium-based glass.
AB  - OBJECTIVE: This study evaluated the incorporation of niobophosphate bioactive
      glass (NbG) fillers into a commercial adhesive resin. MATERIALS AND METHODS: The
      silanized (NbGs) or non-silanized (NbG) NbG was added to the commercial adhesive
      system One Step (OS) at 30% by weight; unfilled adhesive served as control. The
      bioactivity of adhesives was analyzed by SEM and FTIR/ATR after 28 days in PBS.
      The adhesives were evaluated as regards microtensile bond strength immediately
      and after six months (n = 6); degree of conversion (n = 3), microhardness (n =
      5); and radiopacity (n = 3). Data from each test were submitted to ANOVA and
      Tukey tests (P <0.05). RESULTS: FTIR/ATR analysis showed phosphate and carbonate
      precipitates on the NbG adhesive specimen surface. Statistical analysis of
      microtensile bond strength values showed that material x time interaction was not
      significant, but NbG group values were similar to those of unfilled adhesive (p
      <0.05). Addition of NbG did not alter the degree of conversion, but did increase
      microhardness and radiopacity values of the adhesive systems compared with those
      of the control group (OS). Incorporation of NbG into the adhesive system did not
      compromise the properties of the adhesive. CONCLUSION: A smart adhesive system
      with bioactive properties, high radiopacity, microhardness, and similar bond
      strength and degree of conversion was obtained by incorporating 30% by weight of
      NbG.

PMID- 29169096
TI  - Neuromuscular compensatory strategies at the trunk and lower limb are not
      resolved following an ACL reconstruction.
AB  - BACKGROUND: Following anterior cruciate ligament reconstruction (ACLR), patients
      present with greater trunk ipsilateral lean, which may affect knee kinetics and
      increase re-injury risk. However, there has been little research into
      neuromuscular factors controlling the trunk and their relation to the knee
      between healthy and ACLR subjects. This is critical to establish in order to
      develop more directed and effective interventions. HYPOTHESIS: As compared to
      healthy control subjects, ACLR subjects will demonstrate increased erector spinae
      and rectus abdominis co-contraction, greater rectus abdominis force and greater
      hamstring force that is correlated to increased forward trunk lean. STUDY DESIGN:
      Cross-sectional study, Level of Evidence: 3. METHODS: Eleven healthy and eleven
      ACLR subjects were matched for age, mass and height. Subjects were asked to run
      at a self-selected speed while instrumented gait analysis was performed. An
      anthropometrically scaled OpenSim model was created for each subject. Trunk and
      hamstring muscle forces from Static Optimization were analyzed at impact peak.
      Additionally, directed co-contraction ratios were calculated for the erector
      spinae and erector spinae/rectus abdominis combinations. RESULTS: ACLR subjects
      showed more balanced erector spinae co-contraction [p<0.01], and greater
      hamstring force [biceps femoris long head (p=0.02), semimembranosus (0.01),
      semitendinosus (0.01)]. There was no statistical difference for any other muscle
      group. CONCLUSION: Despite release to return to sport, ACLR subjects are
      continuing to increase the stiffness of their trunk as well increase their
      hamstring force to potentially reduce anterior tibial translation. CLINICAL
      RELEVANCE: Clinicians may anticipate ACLR subjects using their erector spinae and
      hamstrings to maintain a sense of stability in their trunk and at their knee.

PMID- 29169097
TI  - Altered postural control variability in older-aged individuals with a history of
      lateral ankle sprain.
AB  - The current study aimed to examine postural control performance during a single
      leg balance task in elderly individuals with and without a previous history of
      lateral ankle sprain (LAS). Eighteen adults with a previous history of LAS (mean
      age = 66 years old) and 12 healthy controls (mean age = 65 years old) were
      included in the study. Participants performed three trials of a single-leg
      balance task during an eyes-opened condition for 20-s. Center of pressure (COP)
      trajectories in the anteroposterior (AP) and mediolateral (ML) directions were
      collected with a force plate. The following postural control measures were
      calculated in the AP and ML directions: 1) Sample Entropy (SampEn); 2)
      Approximate Entropy (ApEn); 3) mean of Time-to-Boundary minima (mean TTB); and 4)
      COP velocity (COPV). Older-age participants with a history LAS exhibited lower
      ApEn-AP, SampEn-AP, and SampEn-ML values compared to healthy controls (p < 0.05).
      The information gained from this investigation indicates more rigid postural
      control patterns, less adaptability, and more difficulty maintaining COP during a
      single-leg balance task in adults with a previous history of LAS. Our data
      suggest that there is a need to consider history of musculoskeletal injury when
      evaluating factors for postural control and fall risk in the elderly. Future
      investigations are needed to assess the effect of LAS on age-related declines in
      postural control and discern associations between potential risk factors of fall
      related injuries and LAS in an elderly population.

PMID- 29169098
TI  - Assessing the effects of seawater temperature and pH on the bioaccumulation of
      emerging chemical contaminants in marine bivalves.
AB  - Emerging chemical contaminants [e.g. toxic metals speciation, flame retardants
      (FRs) and perfluorinated compounds (PFCs), among others], that have not been
      historically recognized as pollutants nor their toxicological hazards, are
      increasingly more present in the marine environment. Furthermore, the effects of
      environmental conditions (e.g. temperature and pH) on bioaccumulation and
      elimination mechanisms of these emerging contaminants in marine biota have been
      poorly studied until now. In this context, the aim of this study was to assess,
      for the first time, the effect of warmer seawater temperatures (Delta = + 4
      degrees C) and lower pH levels (Delta = - 0.4 pH units), acting alone or
      combined, on the bioaccumulation and elimination of emerging FRs (dechloranes
      602, 603 and 604, and TBBPA), inorganic arsenic (iAs), and PFCs (PFOA and PFOS)
      in two estuarine bivalve species (Mytilus galloprovincialis and Ruditapes
      philippinarum). Overall, results showed that warming alone or combined with
      acidification promoted the bioaccumulation of some compounds (i.e. dechloranes
      602, 604, TBBPA), but also facilitated the elimination of others (i.e. iAs,
      TBBPA). Similarly, lower pH also resulted in higher levels of dechloranes, as
      well as enhanced iAs, PFOA and PFOS elimination. Data also suggests that, when
      both abiotic stressors are combined, bivalves' capacity to accumulate
      contaminants may be time-dependent, considering significantly drastic increase
      observed with Dec 602 and TBBPA, during the last 10 days of exposure, when
      compared to reference conditions. Such changes in contaminants'
      bioaccumulation/elimination patterns also suggest a potential increase of human
      health risks of some compounds, if the climate continues changing as forecasted.
      Therefore, this first study pointed out the urgent need for further research on
      the effects of abiotic conditions on emerging contaminants kinetics, to
      adequately estimate the potential toxicological hazards associated to these
      compounds and develop recommendations/regulations for their presence in seafood,
      considering the prevailing environmental conditions expected in tomorrow's ocean.

PMID- 29169099
TI  - Exposure to arsenic in tap water and gestational diabetes: A French semi
      ecological study.
AB  - INTRODUCTION: The increase in the prevalence of gestational diabetes mellitus
      (GDM) and its consequences for mother and children prompts research on their risk
      factors including environmental factors. Studies on exposure to arsenic (As) in
      tap water and the risk of GDM have not provided conclusive evidence, particularly
      when levels of exposure were low (from 10 to 50ug As/L). The main objective of
      this study was to assess the association between exposure to As in tap water and
      the risk of GDM. METHODS: A semi-ecological study was conducted from births
      recorded at the University Hospital of Clermont-Ferrand, France, in 2003, 2006
      and 2010. Individual medical/obstetric data were available. As exposure was
      estimated from the concentrations of As measured during sanitary control of tap
      water supplied in the mothers' commune of residence (aggregate data). French
      guidelines for As in tap water were used to identify groups potentially exposed,
      designated "As +" (>= 10ug As/L) and "As -" (< 10ug As/L). Multivariate logistic
      regression analysis was performed. RESULTS: 5053 women (5.7% with a GDM) were
      included. Overall, women in the As + group had a higher risk of GDM than those in
      the As - group (adjusted OR = 1.62; 95%CI: 1.01-2.53). Stratified analysis of pre
      pregnancy body mass index (BMI) showed a positive association only for obese or
      overweight women (adjusted OR = 2.30; 95%CI: 1.13-4.50). CONCLUSION: This French
      semi-ecological study provides additional arguments for an association between As
      exposure and the risk of GDM in particular in a context of low exposure. Further
      studies are needed to assess a potential interaction between As exposure and body
      mass index.

PMID- 29169100
TI  - The G2 erosion model: An algorithm for month-time step assessments.
AB  - A detailed description of the G2 erosion model is presented, in order to support
      potential users. G2 is a complete, quantitative algorithm for mapping soil loss
      and sediment yield rates on month-time intervals. G2 has been designed to run in
      a GIS environment, taking input from geodatabases available by European or other
      international institutions. G2 adopts fundamental equations from the Revised
      Universal Soil Loss Equation (RUSLE) and the Erosion Potential Method (EPM),
      especially for rainfall erosivity, soil erodibility, and sediment delivery ratio.
      However, it has developed its own equations and matrices for the vegetation cover
      and management factor and the effect of landscape alterations on erosion.
      Provision of month-time step assessments is expected to improve understanding of
      erosion processes, especially in relation to land uses and climate change. In
      parallel, G2 has full potential to decision-making support with standardised maps
      on a regular basis. Geospatial layers of rainfall erosivity, soil erodibility,
      and terrain influence, recently developed by the Joint Research Centre (JRC) on a
      European or global scale, will further facilitate applications of G2.

PMID- 29169101
TI  - Contribution of diet and other factors to the observed levels of selected
      perfluoroalkyl acids in serum among US children aged 3-11 years.
AB  - Data from National Health and Nutrition Examination Survey for 2013-2014 for
      children aged 3-11 years (N = 639) were analyzed to evaluate the contribution of
      diet and other factors in variability associated with the observed levels of
      seven perfluoroalkyl acids in serum, namely, 2(N-methyl-perfluorooctane
      sulfonamide) acetic acid (MPAH), perfluorodecanoic acid (PFDE), perfluorononanoic
      acid (PFNA), perflurorohexane sulfonic acid (PFHxS), linear isomer of PFOA
      (NPFOA), linear isomer of PFOS (NPFOS), and monomethyl isomer of PFOS (MPFOS).
      Diet accounted for a low of 18.6% of the total explained variance in the adjusted
      levels of NPFOA and a high of 72.3% for PFNA. Consumption of meat other than fish
      and poultry was associated with increased levels of NPFOS (beta = 0.00035, p <
      0.01) and MPFOS (beta = 0.00027, p=0.02). However, consumption of fish was
      associated with decreased levels of PFDE (beta = - 0.00058, p=0.01). Consumption
      of eggs was associated with higher levels of PFDE (beta = 0.00105, p=0.04).
      Higher levels of PFHxS were associated with consumption of fruits and juices
      (beta = 0.00019, p = 0.03). Exposure to environmental tobacco smoke in indoor
      environments other than home was associated with 12.6% increase in the levels of
      NPFOA. Boys had higher adjusted geometric mean (AGM) than girls for MPAH (0.88
      vs. 0.70ng/mL, p = 0.04) and NPFOS (2.73 vs. 2.27ng/mL, p = 0.04). Non-Hispanic
      white had higher AGMs than Hispanics for MPAH (0.15 vs. 0.07, p < 0.01), for
      NPFOA (1.98 vs. 1.64ng/mL, p < 0.01), and MPFOS (1.39 vs. 1.18ng/mL, p = 0.03).
      Non-Hispanic white also had higher AGM than non-Hispanic Asians and others for
      PFHxS (0.99 vs. 0.63ng/mL, p < 0.01) and NPFOA (1.98 vs. 1.53ng/mL, p < 0.01).

PMID- 29169102
TI  - A novel framework to evaluate pedestrian safety at non-signalized locations.
AB  - This paper proposes a new framework to evaluate pedestrian safety at non
      signalized crosswalk locations. In the proposed framework, the yielding maneuver
      of a driver in response to a pedestrian is split into the reaction and braking
      time. Hence, the relationship of the distance required for a yielding maneuver
      and the approaching vehicle speed depends on the reaction time of the driver and
      deceleration rate that the vehicle can achieve. The proposed framework is
      represented in the distance-velocity (DV) diagram and referred as the DV model.
      The interactions between approaching vehicles and pedestrians showing the
      intention to cross are divided in three categories: i) situations where the
      vehicle cannot make a complete stop, ii) situations where the vehicle's ability
      to stop depends on the driver reaction time, and iii) situations where the
      vehicle can make a complete stop. Based on these classifications, non-yielding
      maneuvers are classified as "non-infraction non-yielding" maneuvers, "uncertain
      non-yielding" maneuvers and "non-yielding" violations, respectively. From the
      pedestrian perspective, crossing decisions are classified as dangerous crossings,
      risky crossings and safe crossings accordingly. The yielding compliance and
      yielding rate, as measures of the yielding behavior, are redefined based on these
      categories. Time to crossing and deceleration rate required for the vehicle to
      stop are used to measure the probability of collision. Finally, the framework is
      demonstrated through a case study in evaluating pedestrian safety at three
      different types of non-signalized crossings: a painted crosswalk, an unprotected
      crosswalk, and a crosswalk controlled by stop signs. Results from the case study
      suggest that the proposed framework works well in describing pedestrian-vehicle
      interactions which helps in evaluating pedestrian safety at non-signalized
      crosswalk locations.

PMID- 29169103
TI  - Impact of roadway geometric features on crash severity on rural two-lane
      highways.
AB  - This study examines the impact of a wide range of roadway geometric features on
      the severity outcomes of crashes occurred on rural two-lane highways. We argue
      that crash data have a hierarchical structure which needs to be addressed in
      modeling procedure. Moreover, most of previous studies ignored the impact of
      geometric features on crash types when developing crash severity models. We
      hypothesis that geometric features are more likely to determine crash type, and
      crash type together with other occupant, environmental and vehicle
      characteristics determine crash severity outcome. This paper presents an
      application of multilevel models to successfully capture both hierarchical
      structure of crash data and indirect impact of geometric features on crash
      severity. Using data collected in Illinois from 2007 to 2009, multilevel ordered
      logit model is developed to quantify the impact of geometric features and
      environmental conditions on crash severity outcome. Analysis results revealed
      that there is a significant variation in severity outcomes of crashes occurred
      across segments which verifies the presence of hierarchical structure. Lower risk
      of severe crashes is found to be associated with the presence of 10-ft lane
      and/or narrow shoulders, lower roadside hazard rate, higher driveway density,
      longer barrier length, and shorter barrier offset. The developed multilevel model
      offers greater consistency with data generating mechanism and can be utilized to
      evaluate safety effects of geometric design improvement projects.

PMID- 29169104
TI  - Reconciling ethical and economic conceptions of value in health policy using the
      capabilities approach: A qualitative investigation of Non-Invasive Prenatal
      Testing.
AB  - When evaluating new morally complex health technologies, policy decision-makers
      consider a broad range of different evaluations, which may include the
      technology's clinical effectiveness, cost effectiveness, and social or ethical
      implications. This type of holistic assessment is challenging, because each of
      these evaluations may be grounded in different and potentially contradictory
      assumptions about the technology's value. One such technology where evaluations
      conflict is Non-Invasive Prenatal Testing (NIPT). Cost-effectiveness evaluations
      of NIPT often assess NIPT's ability to deliver on goals (i.e preventing the birth
      of children with disabilities) that social and ethical analyses suggest it should
      not have. Thus, cost effectiveness analyses frequently contradict social and
      ethical assessments of NIPT's value. We use the case of NIPT to explore how
      economic evaluations using a capabilities approach may be able to capture a
      broader, more ethical view of the value of NIPT. The capabilities approach is an
      evaluative framework which bases wellbeing assessments on a person's abilities,
      rather than their expressed preferences. It is linked to extra-welfarist
      approaches in health economic assessment. Beginning with Nussbaum's capability
      framework, we conducted a directed qualitative content analysis of interview data
      collected in 2014 from 27 Canadian women with personal experience of NIPT. We
      found that eight of Nussbaum's ten capabilities related to options, states, or
      choices that women valued in the context of NIPT, and identified one new
      capability. Our findings suggest that women value NIPT for its ability to provide
      more and different choices in the prenatal care pathway, and that a capabilities
      approach can indeed capture the value of NIPT in a way that goes beyond measuring
      health outcomes of ambiguous social and ethical value. More broadly, the
      capabilities approach may serve to resolve contradictions between ethical and
      economic evaluations of health technologies, and contribute to extra-welfarist
      approaches in the assessment of morally complex health technologies.

PMID- 29169105
TI  - Constitutive redox and phosphoproteome changes in multiple herbicide resistant
      Avena fatua L. are similar to those of systemic acquired resistance and systemic
      acquired acclimation.
AB  - Plants are routinely confronted with numerous biotic and abiotic stressors, and
      in response have evolved highly effective strategies of systemic acquired
      resistance (SAR) and systemic acquired acclimation (SAA), respectively. A much
      more evolutionarily recent abiotic stress is the application of herbicides to
      control weedy plants, and their intensive use has selected for resistant weed
      populations that cause substantial crop yield losses and increase production
      costs. Non-target site resistance (NTSR) to herbicides is rapidly increasing
      worldwide and is associated with alterations in generalized stress defense
      networks. This work investigated protein post-translational modifications
      associated with NTSR in multiple herbicide resistant (MHR) Avena fatua, and their
      commonalities with those of SAR and SAA. We used proteomic, biochemical, and
      immunological approaches to compare constitutive protein profiles in MHR and
      herbicide susceptible (HS) A. fatua populations. Phosphoproteome and redox
      proteome surveys showed that post-translational modifications of proteins with
      functions in core cellular processes were reduced in MHR plants, while those
      involved in xenobiotic and stress response, reactive oxygen species
      detoxification and redox maintenance, heat shock response, and intracellular
      signaling were elevated in MHR as compared to HS plants. More specifically, MHR
      plants contained constitutively elevated levels of three protein kinases
      including the lectin S-receptor-like serine/threonine-protein kinase LecRK2, a
      well-characterized component of SAR. Analyses of superoxide dismutase enzyme
      activity and protein levels did not reveal constitutive differences between MHR
      and HS plants. The overall results support the idea that herbicide stress is
      perceived similarly to other abiotic stresses, and that A. fatua NTSR shares
      analogous features with SAR and SAA. We speculate that MHR A. fatua's previous
      exposure to sublethal herbicide doses, as well as earlier evolution under a
      diversity of abiotic and biotic stressors, has led to a heightened state of
      stress preparedness that includes NTSR to a number of unrelated herbicides.

PMID- 29169106
TI  - The transcriptomic changes of Huipizhi Heidou (Glycine max), a nematode-resistant
      black soybean during Heterodera glycines race 3 infection.
AB  - Glycine max (soybean) is an extremely important crop, representing a major source
      of oil and protein for human beings. Heterodera glycines (soybean cyst nematode,
      SCN) infection severely reduces soybean production; therefore, protecting soybean
      from SCN has become an issue for breeders. Black soybean has exhibited a
      different grade of resistance to SCN. However, the underlying mechanism of
      Huipizhi Heidou resistance against SCN remains elusive. The Huipizhi Heidou
      (ZDD2315) and race 3 of Heterodera glycines were chosen to study the mechanism of
      resistance via examination of transcriptomic changes. After 5, 10, and 15days of
      SCN infection, whole roots were sampled for RNA extraction, and uninfected
      samples were simultaneously collected as a control. 740, 1413, and 4925 genes
      were isolated by padj (p-value adjusted)<0.05 after 5, 10, and 15days of the
      infection, respectively, and 225 differentially expressed genes were overlapped
      at all the time points. We found that the differentially expressed genes (DEGs)
      at 5, 10, and 15days after infection were involved in various biological function
      categories; in particular, induced genes were enriched in defense response,
      hormone mediated signaling process, and response to stress. To verify the
      pathways observed in the GO and KEGG enrichment results, effects of hormonal
      signaling in cyst-nematode infection were further examined via treatment with IAA
      (indo-3-acetic acid), salicylic acid (SA), gibberellic acid (GA), jasmonic acid
      (JA), and ethephon, a precursor of ethylene. The results indicate that five
      hormones led to a significant reduction of J2 number in the roots of Huipizhi
      Heidou and Liaodou15, representing SCN-resistant and susceptible lines,
      respectively. Taken together, our analyses are aimed at understanding the
      resistance mechanism of Huipizhi Heidou against the SCN race 3 via the dissection
      of transcriptomic changes upon J2 infection. The data presented here will help
      further research on the basis of soybean and cyst-nematode interaction.

PMID- 29169107
TI  - Mechanistic insights into alginate fouling caused by calcium ions based on
      terahertz time-domain spectra analyses and DFT calculations.
AB  - Fouling mechanisms underlying the filtration behaviors of alginate solution
      caused by calcium addition were investigated by Terahertz time-domain
      spectroscopy (THz-TDS) and density functional theory (DFT) techniques. Filtration
      tests showed that specific filtration resistance (SFR) of alginate solution (0.75
      g L-1) monotonously increased with calcium addition at a relatively low range of
      calcium concentration (0-1.0 mM), and SFR (2.61 * 1015 m kg-1) of alginate
      solution with 1.0 mM calcium addition was extremely high as compared with sludge
      suspension. Characterizations by X-ray photoelectric spectroscopy (XPS), Fourier
      transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA)
      showed that the composition of functional groups, elements and thermal stability
      of alginate was not apparently affected by calcium concentration. Howbeit, THz
      TDS spectra showed that calcium addition caused structural variation of alginate
      polymer in solution. DTF calculation results showed that initial binding of
      alginate chains induced by calcium ions preferentially occurred in intermolecular
      other than intramolecular, and moreover, the two alginate chains bridged by a
      calcium atom tend to stretch in a tetrahedron structure (cross to each other)
      other than parallel to each other. According to these results, "chemical
      potential gap" depicted by Flory-Huggins theory was suggested to be responsible
      for the filtration behaviors of alginate solution caused by calcium addition.
      This study provided the mechanistic insights into membrane fouling.

PMID- 29169108
TI  - Identification of mutagenic transformation products generated during oxidation of
      3-methyl-4-nitrophenol solutions by orbitrap tandem mass spectrometry and
      quantitative structure-activity relationship analyses.
AB  - We used Ames assays to investigate the effects of ozonation (designated O3),
      ozonation followed by chlorination (O3/Cl), an advanced oxidation process (AOP,
      UV/H2O2), and AOP followed by chlorination (AOP/Cl) on the mutagenicity of
      solutions of 3-methyl-4-nitrophenol (3M4NP), a major environmental degradation
      product of the organophosphorus insecticide fenitrothion. Whereas O3 did not
      induce mutagenicity, O3/Cl, AOP, and AOP/Cl converted 3M4NP into mutagenic
      transformation products (TPs). Using liquid chromatography-mass spectrometry, we
      detected a total of 138 peaks in the solutions subjected to O3/Cl, AOP, and
      AOP/Cl. To elucidate the TPs responsible for the observed mutagenicity, we
      performed simple regression analyses of the relationship between the area of each
      peak and the observed mutagenicity of samples withdrawn periodically during each
      oxidation process. The area of each of 10 peaks was found to be positively
      correlated (r2 >= 0.8) with the observed mutagenicity, suggesting that the TPs
      corresponding to these peaks contributed to the mutagenicity. After taking into
      account the consistency of mutagenicity induction by the oxidation processes and
      analyzing the peaks by tandem mass spectrometry, we identified 3 TPs,
      corresponding to 6 peaks, as candidate mutagens. These TPs were assessed by means
      of 4 quantitative structure-activity relationship (QSAR) models, and all 3 were
      predicted to be mutagenic by at least one model. This result was consistent with
      our assumption that these TPs were mutagens. Ames assays of an authentic sample
      of one of the 3 TPs revealed that it did not contribute to the mutagenicity. This
      left 3-methoxy-4-nitrophenol and 2-[(E)-[(2,5-dihydroxyphenyl) methylidene]amino]
      5-dihydroxybenzaldehyde on the list of mutagens suspected of contributing to the
      mutagenicity induced by AOP. No TPs were identified as candidate mutagens
      responsible for the mutagenicity induced by O3/Cl and AOP/Cl.

PMID- 29169109
TI  - Mechanism and efficiency of contaminant reduction by hydrated electron in the
      sulfite/iodide/UV process.
AB  - Advanced reduction by the extremely strong reducing species, hydrated electron
      (eaq-), is a promising and viable approach to eliminate a wide variety of
      persistent and toxic contaminants. In this study, we proposed a sulfite/iodide/UV
      process, which offered efficient production of eaq- for contaminant reduction.
      Using monochloroacetic acid (MCAA) as a simple eaq- probe, the availability of
      eaq- was assessed, and the mechanism involving the roles of S(IV) and iodide in
      the process was elucidated. A pronounced synergistic effect of S(IV) and iodide
      was observed in MCAA reductive dechlorination. The efficiency was much more
      dependent on the iodide concentration due to its higher absorptivity and quantum
      yield of eaq-. S(IV) played a dual role by producing eaq- via photoionization of
      SO32- and by reducing the reactive iodine species formed to avoid their
      scavenging of eaq-. When S(IV) was available, cycling of iodide occurred,
      favoring the constant eaq- production. The formation and transformation kinetics
      of sulfite radical were studied to verify the roles of S(IV) and iodide in the
      process. A kinetic model of MCAA dechlorination was also developed to quantify
      the eaq--initiated reduction efficiency, highlighting the effects of S(IV),
      iodide, and pH. High pH favored the reduction, and the process was still
      effective in field surface water. This study underscores the importance of
      producing eaq- efficiently and of minimizing the eaq- scavenging of intermediates
      inherently formed and accumulated, and highlights the potential of the
      sulfite/iodide/UV process to efficiently eliminate recalcitrant contaminants.

PMID- 29169110
TI  - Disorder of gut amino acids metabolism during CKD progression is related with gut
      microbiota dysbiosis and metagenome change.
AB  - Chronic kidney disease (CKD) is a worldwide public health problem. Uremic
      retention solutes such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are
      accumulated in CKD patients and are associated with the incidence of CKD
      progression. Amino acids are the major precursors of uremic retention solutes in
      gut. The dynamic change of amino acid metabolism in the gut during CKD
      progression has not been reported previously. In this paper, we studied the
      dynamic change of gut IS/PCS precursor and amino acid metabolism profile during
      CKD progression in 5/6 nephrectomized (5/6Nx) rats model. The related gut
      microbiota and metagenome profile was also studied. Rat plasma, urine and feces
      were collected at different time points after nephrectomization. Plasma IS and
      PCS, fecal indole (the precursor of IS), p-cresol (the precursor of PCS) and 19
      kinds of amino acids were analyzed by LC-MS. During CKD progression, 5/6 Nx rats
      showed increased plasma IS, PCS concentration and increased fecal indole, p
      cresol concentration. 5/6 Nx rats also showed disordered gut amino acids
      metabolism profile which became more significant along with the progession of
      CKD. The abundance of some specific gut bacteria also changed significantly in
      5/6 Nx rats. The 16S rDNA sequencing data of gut microbiota was further analyzed
      by an online tool PICRUSt, a large-scale computational method for metagenomes
      prediction with 16S rDNA sequencing data. The content of each gene was compared
      between the two groups by Mann-Whitney U test, and then the significantly
      regulated genes in 5/6 Nx group were subjected to KEGG website. The amino acid
      metabolism related genes were picked out. Most of these genes are more abundant
      in 5/6 Nx groups. Our study showed that gut amino acids metabolism profile was
      disordered with CKD progression, which was highly related to the gut microbiota
      dysbiosis and metagenome change. And that regulation of gut amino acids
      metabolism pathway may be a possible way to intervene the progression of CKD.

PMID- 29169112
TI  - Analysis of unbound plasma concentration of oxcarbazepine and the 10
      hydroxycarbazepine enantiomers by liquid chromatography with tandem mass
      spectrometry in healthy volunteers.
AB  - This study describes the development and validation of a method for the analysis
      of unbound plasma concentrations of oxcarbazepine (OXC) and of the enantiomers of
      its active metabolite 10-hydroxycarbazepine (MHD) [S-(+)- and R-(-)-MHD] using
      liquid chromatography with tandem mass spectrometry (LC-MS/MS). Additionally, the
      free fraction of the drug is described in healthy volunteers (n=12) after the
      oral administration of 300mg OXC/12h for 5days. Plasma aliquots of 200MUL were
      submitted to ultrafiltration procedure and 50MUL of the ultrafiltrate were
      extracted with a mixture of tert-butyl methyl ether:dichloromethane (2:1, v/v).
      OXC and the MHD enantiomers were separated on a OD-H chiral phase column. The
      method was linear in the range of 4.0-2.0MUg/mL for OXC and of 20.0-6.0MUg/mL
      plasma for the MHD enantiomers. The limit of quantification was 4ng for OXC and
      20ng for each MHD enantiomer/mL plasma. The intra- and inter-day precision and
      inaccuracy were less than 15%. The free fraction at the time of peak plasma
      concentration of OXC was 0.27 for OXC, 0.37 for S-(+)-MHD and 0.42 for R-(-)-MHD.
      Enantioselectivity in the free fraction of MHD was observed, with a higher
      proportion of R-(-)-MHD compared to S-(+)-MHD.

PMID- 29169111
TI  - Identification of phenolic components via LC-MS analysis and biological
      activities of two Centaurea species: C. drabifolia subsp. drabifolia and C.
      lycopifolia.
AB  - The Centaurea genus has great potential in traditional systems and has attracted
      much interest in the design of novel drug formulations. The present study was
      focused on the chemical fingerprints and biological properties of Centaurea
      drabifolia subsp. drabifolia and Centaurea lycopifolia extracts.
      Spectrophotometric and LC-MS techniques were used to establish the chemical
      profiles of the studied extracts. Enzyme inhibitory potential was assessed
      against key enzymes linked to global health problems, namely neurodegenerative
      diseases (acetylcholinesterase), pigmentation (tyrosinase), and diabetes (alpha
      amylase and alpha-glucosidase). The antimicrobial propensities of the extract
      were evaluated against 16 bacterial and fungal strains using the microdilution
      method. The antioxidant abilities were assessed using DPPH and ABTS radical
      scavenging, ferric, and cupric reducing powers, phosphomolybdenum, and ferrous
      metal chelation. The total phenolic compounds varied from 18.33 to 32.84mgGAE/g
      extract. Total flavonoid content of the extracts were in the range of 2.88
      22.39mgRE/g extract. Methanol and water extracts showed stronger antioxidant
      abilities compared to the ethyl acetate extracts. However, the latter extracts
      were most efficient towards the target enzymes (except for tyrosinase). The water
      extracts also exerted considerable antimicrobial effects. Findings from the
      present work tend to support the idea that C. drabifolia subsp. drabifolia and C.
      lycopifolia may be utilized as effective bio-resources for designing novel health
      promoting products or ingredients. It is anticipated that results amassed from
      this still will open new avenues for research and contribute towards establishing
      primary data on these species for designing novel phytopharmaceuticals.

PMID- 29169113
TI  - A rapid and simple HPLC-MS/MS method for the simultaneous quantification of
      valproic acid and its five metabolites in human plasma and application to study
      pharmacokinetic interaction in Chinese epilepsy patients.
AB  - Valproic acid(VPA) is a classic drug that used to treat epilepsy in monotherapy
      or combination with other anticonvulsant drugs such as lamotrigine (LTG).
      Although it was reported that VPA could increase lamotrigine trough concentration
      in clinical practice, there was no report about the effect of LTG on the trough
      concentration of VPA and its main metabolites, such as 4-ene-VPA, 3-OH-VPA, 4-OH
      VPA, 3-keto-VPA, 2-PGA which are related to the therapeutic and toxic effects of
      VPA. In this study, a simple and rapid method for the simultaneous determination
      of VPA and its five metabolites in human plasma using HPLC-MS/MS was developed
      for the first time. Benzoic acid was used as an internal standard (IS).
      Separation was performed on a Hypersil GOLD C18 column by isocratic elution using
      acetonitrile: 10mM ammonium acetate solution (90:10, v/v) as mobile phase at a
      flow rate of 0.3mL/min. A triple quadrupole mass spectrometer operating in the
      negative ion-switching, electron spray ionization mode with selection reaction
      monitoring (SRM) was employed to determine transitions of m/z 143.183->143.183,
      157.033->113.165, 173.017->129.074, 159.058->101.082, 140.870->140. 870, 159.049
      >123.076, 121.035->77.136 for VPA, 2-PGA, 3-keto-VPA, 3-OH-VPA, 4-ene-VPA, 4-OH
      VPA and IS, respectively. The method also afforded satisfactory results in terms
      of sensitivity, specificity, precision (intra- and inter-batch), accuracy,
      recovery, matrix effect and stability. This method was successfully applied to
      evaluate the effect of LTG on the trough concentration of VPA, 2-PGA, 3-keto-VPA,
      3-OH-VPA, 4-ene-VPA, 4-OH-VPA in Chinese epilepsy patients. The result showed
      that there was no significant difference in the concentration of VPA and its five
      metabolites between patients in VPA monotherapy and patients in therapy combining
      VPA with LTG.

PMID- 29169116
TI  - p-Nitrophenol degradation by Fenton's oxidation in a bubble column reactor.
AB  - This paper reports on a study of the oxidation of p-nitrophenol (PNP) in a bubble
      column reactor (BCR). The use of the air stream aimed to provide perfect mixing
      in the liquid phase, which was successfully achieved and checked experimentally;
      there were no concentration gradients along the column, even at the lowest air
      flow rate used (Q = 1 mL/min at room temperature and atmospheric pressure). The
      effect of the operating variables was assessed, and a total reduction of PNP was
      reached, as well as mineralization of 49.2%, oxidant consumption of 90.3%, and
      with an efficiency of use - etaH2O2 - of 0.09 mg C/mg H2O2, under the best
      operating conditions found - Q = 1 mL/min, [H2O2] = 1.6 g/L, [Fe2+] = 80 mg/L, pH
      = 3.0 and T = 22-24  degrees C - (after 120 min of reaction). Following this,
      various strategies were developed for improving the mineralization rate; it was
      found that the addition of H2O2 every 5 min and readjusting the pH after 30 min
      of reaction allow the attainment of a much higher TOC removal (75.1%) and
      efficiency of oxidant use (etaH2O2 = 0.17 mg C/mg H2O2) with less oxidant. A
      reaction mechanism was proposed, based on intermediates identified that include p
      nitrocatechol - PNC, p-benzoquinone - PB, hydroquinone - HQ - and carboxylic
      acids (oxalic, maleic and fumaric). Since the performance achieved in the BCR was
      good, and very similar to that obtained in a conventional batch reactor, it was
      possible to verify the efficacy of carrying out the Fenton process in this
      reactor configuration, which in our future work will focus on the treatability of
      industrial effluents.

PMID- 29169114
TI  - Evaluation of antiparkinson activity of PTUPB by measuring dopamine and its
      metabolites in Drosophila melanogaster: LC-MS/MS method development.
AB  - Soluble epoxide hydrolase (sEH) inhibition is reported to elevate endogenous
      epoxyeicosatrienoic acids (EET's), which are known to play an important role in
      neuroprotection by inhibiting oxidative stress and neuroinflammation. In the
      present study, PTUPB, a dual inhibitor of sEH and COX-2, has been tested for its
      antiparkinson activity against rotenone (ROT) induced neurodegeneration in
      Drosophila model of Parkinson's disease (PD). To determine the efficacy and brain
      bioavailability of PTUPB a simple, rapid and sensitive LC-MS/MS method was
      developed and validated for the estimation of PTUPB (Method-I), dopamine (DA) and
      its metabolites (Method-II) in fly head. Mass spectrometric acquisitions of
      analytes signals were performed in positive and negative electron spray
      ionization MRM mode by monitoring the daughter ions. The isocratic elution using
      formic acid (0.1% v/v) and acetonitrile (20:80v/v) (for method I), and acetic
      acid (0.1% v/v) and methanol (for method II) on Jones C18 was carried out to
      achieve the separation. The results of brain PTUPB, DA and its metabolites
      estimation shows a dose dependent increase in PTUPB concentration and a dose
      dependent prevention of ROT induced changes in DA and its metabolites levels
      (p<0.05), indicating a significant neuroprotection activity of PTUPB. In the
      present study, we have successfully developed and validated LC-MS/MS methods to
      identify and quantify PTUPB, DA and its metabolites using a UFLC-ESI-QqQ mass
      spectrometer for the screening of neuroprotective agents in Drosophila
      Melanogaster.

PMID- 29169117
TI  - 3D correction over 2years with anterior vertebral body growth modulation: A
      finite element analysis of screw positioning, cable tensioning and postoperative
      functional activities.
AB  - BACKGROUND: Anterior vertebral body growth modulation is a fusionless
      instrumentation to correct scoliosis using growth modulation. The objective was
      to biomechanically assess effects of cable tensioning, screw positioning and post
      operative position on tridimensional correction. METHODS: The design of
      experiments included two variables: cable tensioning (150/200N) and screw
      positioning (lateral/anterior/triangulated), computationally tested on 10
      scoliotic cases using a personalized finite element model to simulate spinal
      instrumentation, and 2years growth modulation with the device. Dependent
      variables were: computed Cobb angles, kyphosis, lordosis, axial rotation and
      stresses exerted on growth plates. Supine functional post-operative position was
      simulated in addition to the reference standing position to evaluate
      corresponding growth plate's stresses. FINDINGS: Simulated cable tensioning and
      screw positioning had a significant impact on immediate and after 2years Cobb
      angle (between 5 degrees -11 degrees , p<0.01). Anterior screw positioning
      significantly increased kyphosis after 2years (6 degrees -8 degrees , p=0.02).
      Triangulated screw positioning did not significantly impact axial rotation but
      significantly reduced kyphosis (8 degrees -10 degrees , p=0.001). Growth plates'
      stresses were increased by 23% on the curve's convex side with cable tensioning,
      while screw positioning rather affected anterior/posterior distributions. Supine
      position significantly affected stress distributions on the apical vertebra
      compared to standing position (respectively 72% of compressive stresses on convex
      side vs 55%). INTERPRETATION: This comparative numerical study showed the
      biomechanical possibility to adjust the fusionless instrumentation parameters to
      improve correction in frontal and sagittal planes, but not in the transverse
      plane. The convex side stresses increase in the supine position may suggest that
      growth modulation could be accentuated during nighttime.

PMID- 29169115
TI  - Prolonged oxidative stress down-regulates Early B cell factor 1 with inhibition
      of its tumor suppressive function against cholangiocarcinoma genesis.
AB  - Early B cell factor 1 (EBF1) is a transcription factor involved in the
      differentiation of several stem cell lineages and it is a negative regulator of
      estrogen receptors. EBF1 is down-regulated in many tumors, and is believed to
      play suppressive roles in cancer promotion and progression. However, the
      functional roles of EBF1 in carcinogenesis are unclear. Liver fluke-infection
      associated cholangiocarcinoma (CCA) is an oxidative stress-driven cancer of bile
      duct epithelium. In this study, we investigated EBF1 expression in tissues from
      CCA patients, CCA cell lines (KKU-213, KKU-214 and KKU-156), cholangiocyte
      (MMNK1) and its oxidative stress-resistant (ox-MMNK1-L) cell lines. The formation
      of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was used as an oxidative stress
      marker. Our results revealed that EBF1 expression was suppressed in cancer cells
      compared with the individual normal bile duct cells at tumor adjacent areas of
      CCA tissues. CCA patients with low EBF1 expression and high formation of 8-oxodG
      were shown to correlate with poor survival. Moreover, EBF1 was suppressed in the
      oxidative stress-resistant cell line and all of CCA cell lines compared to the
      cholangiocyte cell line. This suggests that prolonged oxidative stress suppressed
      EBF1 expression and the reduced EBF1 level may facilitate CCA genesis. To
      elucidate the significance of EBF1 suppression in CCA genesis, EBF1 expression of
      the MMNK1 cell line was down-regulated by siRNA technique, and its effects on
      stem cell properties (CD133 and Oct3/4 expressions), tumorigenic properties (cell
      proliferation, wound healing and cell migration), estrogen responsive gene
      (TFF1), estrogen-stimulated wound healing, and cell migration were examined. The
      results showed that CD133, Oct3/4 and TFF1 expression levels, wound healing, and
      cell migration of EBF1 knockdown-MMNK1 cells were significantly increased. Also,
      cell migration of EBF1-knockdown cells was significantly enhanced after 17beta
      estradiol treatment. Our findings suggest that EBF1 down-regulation via oxidative
      stress induces stem cell properties, tumorigenic properties and estrogen
      responses of cholangiocytes leading to CCA genesis with aggressive clinical
      outcomes.

PMID- 29169118
TI  - Characterization of a microbial polysaccharide-based bioflocculant and its anti
      inflammatory and pro-coagulant activity.
AB  - We describe a novel bioflocculant, MBF-15, which is an exopolysaccharide
      extracted from the alkaliphilic bacterium Paenibacillus jamilae. The biophysical
      characteristics of MBF-15 were determined using Fourier transform infrared
      spectroscopy and X-ray photoelectron spectroscopy. MBF-15 was also evaluated for
      its biocompatibility by examining its inflammatory, coagulant, and hemostatic
      properties in vitro and in vivo. Pretreatment of peripheral blood mononuclear
      cells with MBF-15 inhibited lipopolysaccharide-stimulated expression of inducible
      nitric oxide synthase, production of nitric oxide, and secretion of pro
      inflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6.
      In addition, MBF-15 increased both mRNA and protein levels of the anti
      inflammatory cytokines transforming growth factor-beta and IL-10. The
      hemocompatibility of MBF-15 was investigated by measuring the hemolysis ratio and
      clotting times. MBF-15 had high pro-thrombogenic activity but was not hemolytic.
      In a rat model, MBF-15 showed superior hemostatic properties compared with
      chitosan. Thus, MBF-15 offers a promising combination of anti-inflammatory and
      pro-coagulant properties that may be useful for hemostasis in a variety of
      clinical settings.

PMID- 29169119
TI  - OBP fused with cell-penetrating peptides promotes liposomal transduction.
AB  - Cell-penetrating peptides (CPPs) have been applied as novel transport systems
      with the ability to facilitate the delivery of peptides, proteins, and
      oligonucleotides into cells. Herein, we designed different fusion proteins
      composed by pig odorant binding protein (OBP-I) and three CPPs, namely Tat, pVEC
      and Pep-1. A new methodology using liposomes as reservoirs and OBP:CPPs as
      carriers was developed as an advanced system to capture odorant molecules. 1
      aminoanthracene (1-AMA) was used as a model molecule to evaluate the transduction
      ability of OBP:CPPs into the reservoirs. The transduction efficiency was
      dependent on the initial capacity of OBP:CPPs to bind 1-AMA and on the
      penetration of liposomes promoted by the CPPs. An encapsulation efficiency of 42%
      was obtained with OBP:Tat fusion protein. The presence of Tat peptide increased
      the 1-AMA transduction of 1.3 and 2.5 fold compared with Pep-1 and pVEC,
      respectively. This work expands the application of OBPs and CPPs on the design of
      promising capture and delivery systems for textile and cosmetic applications.

PMID- 29169120
TI  - Soybean peroxidase immobilized onto silica-coated superparamagnetic iron oxide
      nanoparticles: Effect of silica layer on the enzymatic activity.
AB  - Peroxidase immobilization onto magnetic supports is considered an innovative
      strategy for the development of technologies that involves enzymes in wastewater
      treatment. In this work, magnetic biocatalysts were prepared by immobilization of
      soybean peroxidase (SBP) onto different silica-coated superparamagnetic iron
      oxide nanoparticles. The obtained magnetic biocatalysts were tested for the
      degradation of malachite green (MG), a pollutant often found in industrial
      wastewaters and with significant drawbacks for the human and environmental
      health. A deep physicochemical characterization of the materials was performed by
      means of X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR),
      High Resolution-Transmission Electron Microscope (HR-TEM) and magnetization
      measurements among others techniques. Results showed high immobilization yield of
      SBP onto nanomaterials with excellent properties for magnetic recoverability. A
      partial loss of activity with respect to free SBP was observed, compatible with
      the modification of the conformational structure of the enzyme after
      immobilization. The structural modification depended on the amount (and
      thickness) of silica present in the hybrid materials and the activity yield of
      43% was obtained for the best biocatalyst. Thermal stability and reusability
      capacity were also evaluated.

PMID- 29169121
TI  - Perceptions of firearms and suicide: The role of misinformation in storage
      practices and openness to means safety measures.
AB  - BACKGROUND: Firearm ownership and unsafe storage increase risk for suicide.
      Little is known regarding factors that influence storage practices and
      willingness to engage in means safety. METHODS: Utilizing Amazon's Mechanical
      Turk program, we recruited an online sample of 300 adults living in the US who
      own at least one firearm. Firearm storage practices and openness to means safety
      measures were assessed using items designed for this study. Data were collected
      and analyzed in 2017. RESULTS: Firearms stored in non-secure locations and
      without a locking device were associated with lower beliefs in the relationship
      between firearm storage and suicide risk. Fearlessness about death moderated the
      association between current secure versus non-secure storage and beliefs
      regarding firearm storage and suicide risk, in that storage practices and beliefs
      were more strongly related at higher levels of fearlessness about death. For both
      secure and locked storage of a firearm, there was a significant indirect effect
      of current storage practices on willingness to engage in means safety in the
      future through current beliefs regarding the relationship between firearm storage
      and suicide risk. Unsafe storage practices were largely associated with an
      unwillingness to store firearms more safely or to allow a trusted peer to
      temporarily store the firearm outside the home in order to prevent their own or
      someone else's suicide. LIMITATIONS: Self-report and cross-sectional data were
      used. Results may not generalize to non-firearm owners. CONCLUSIONS: Firearm
      owners are prone to inaccurate beliefs about the relationship between firearms
      and suicide. These beliefs may influence both current firearm storage practices
      and the willingness to engage in means safety.

PMID- 29169122
TI  - PTSD with and without dissociation in young children exposed to interpersonal
      trauma.
AB  - BACKGROUND: A Dissociative Subtype of Posttraumatic Stress Disorder (PTSD) was
      added to the DSM-5, but little is known about this symptom pattern in young
      children exposed to trauma. Tailoring treatment to traumatized young children
      requires understanding the different patterns of trauma-related symptomatology
      and important correlates. The current study tested the hypothesis that type and
      number of child traumatic events, caregiver trauma exposure, and caregiver
      symptomatology would predict whether traumatized young children presented with
      PTSD, PTSD with clinical dissociation, or non-clinical trauma symptoms. METHODS:
      A multinomial regression was conducted using data collected from an ethnically
      and economically diverse sample of 297 trauma-exposed children between the ages
      of 3 and 6 and their caregivers. Based on parent-report on a well-validated
      measure of trauma symptoms, children were categorized into three groups: non
      clinical (n = 128), PTSD only (n = 104), or PTSD with dissociation (PTSD-DISS; n
      = 65). Predictors included trauma exposure, parent trauma symptoms, and child
      sex. RESULTS: Girls were twice more likely than boys to be in the PTSD-DISS
      group; sexually abused children were almost three times as likely to be in the
      PTSD-DISS group; and, for every unit increase in parent avoidance symptoms or
      number of traumatic events, the odds of being in the PTSD-DISS group increased
      significantly. LIMITATIONS: Given the cross-sectional study design, conclusions
      cannot be drawn regarding causality. Measures were completed by a single
      reporter. CONCLUSIONS: Findings suggest that subgroups of children may be
      especially vulnerable to comorbid PTSD and dissociation. Implications for
      treatment are discussed.

PMID- 29169123
TI  - The comparative effectiveness of electroencephalographic indices in predicting
      response to escitalopram therapy in depression: A pilot study.
AB  - BACKGROUND: This study aims to compare the effectiveness of EEG frequency band
      activity including interhemispheric asymmetry and prefrontal theta cordance in
      predicting response to escitalopram therapy at 8-weeks post-treatment, in a multi
      site initiative. METHODS: Resting state 64-channel EEG data were recorded from 44
      patients with a diagnosis of major depressive disorder (MDD) as part of a larger,
      multisite discovery study of biomarkers in antidepressant treatment response,
      conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND).
      Clinical response was measured at 8-weeks post-treatment as change from baseline
      Montgomery-Asberg Depression Rating Scale (MADRS) score of 50% or more. EEG
      measures were analyzed at (1) pre-treatment baseline (2) 2 weeks post-treatment
      and (3) as an ''early change" variable defined as change in EEG from baseline to
      2 weeks post-treatment. RESULTS: At baseline, treatment responders showed
      elevated absolute alpha power in the left hemisphere while non-responders showed
      the opposite. Responders further exhibited a cortical asymmetry in the parietal
      region. Groups also differed in pre-treatment relative delta power with
      responders showing greater power in the right hemisphere over the left while non
      responders showed the opposite. At 2 weeks post-treatment, responders exhibited
      greater absolute beta power in the left hemisphere relative to the right and the
      opposite was noted for non-responders. A reverse pattern was noted for absolute
      and relative delta power at 2 weeks post-treatment. Responders exhibited early
      reductions in relative alpha power and early increments in relative theta power.
      Non-responders showed a significant early increase in prefrontal theta cordance.
      CONCLUSIONS: Hemispheric asymmetries in the alpha and delta bands at baseline and
      at 2 weeks post-treatment have moderately strong predictive utility in predicting
      response to antidepressant treatment.

PMID- 29169124
TI  - Dorsomedial frontal cortical metabolic differences of comorbid generalized
      anxiety disorder in refractory major depression: A [18F] FDG PET brain imaging
      study.
AB  - BACKGROUND: Refractory major depressive disorder (MDD) is a severe mental
      disorder, chronic and difficult to treat. Although generalized anxiety disorder
      (GAD) is frequently observed as a comorbid diagnosis, little is known on the
      comorbid neurobiological substrate. Better insights may improve adequate
      treatment algorithms. OBJECTIVE: To examine this poorly understood clinical
      question, we recruited 52 individuals to participate in a [18F] FDG PET brain
      imaging study. METHODS: Twenty-two refractory MDD patients were diagnosed with
      and 15 refractory MDD patients without comorbid GAD. To compare to the none
      depressed state a sample of 15 age and gender matched never-depressed individuals
      were included. RESULTS: Compared to healthy control subjects, all patients showed
      significantly higher metabolic activity in the bilateral parahippocampal areas.
      Compared to MDD patients, healthy subjects displayed significant higher metabolic
      activity in distinct (bi)frontotemporal and parietal cortices. Refractory MDD
      patients without comorbid GAD showed significant higher metabolic activity in the
      dorsomedial parts of the frontal cortex (dmFC). CONCLUSIONS: The impaired dmFC
      metabolic activity observed in comorbid GAD within refractory MDD may be
      indicative of specific emotional dysfunctional top-down processing in this
      subgroup, conform the anxiety state. Additional psychotherapeutic interventions
      may be warranted.

PMID- 29169125
TI  - Functional connectivity between salience, default mode and frontoparietal
      networks in post-stroke depression.
AB  - BACKGROUND: Previous studies have demonstrated altered resting state functional
      connectivity (rsFC) in patients with post-stroke depression (PSD). It remains
      unclear whether rsFC is changed at the network level as was shown for major
      depressive disorder (MDD). To address this question, we investigated rsFC of
      resting sate networks (RSNs) in PSD. METHODS: Eleven subjects with PSD underwent
      fMRI scanning at rest before and after treatment. The severity of depression was
      assessed using the aphasic depression rating scale (ADRS). We performed
      functional network connectivity (FNC) analysis for RSNs, region of interest - FC
      analysis (ROI-FC) and calculation of brain matter volumes in ROIs overlapping
      with RSNs and in other brain regions associated with mood maintenance. RESULTS:
      We found positive correlation of FNC between anterior default mode network (aDMN)
      and salience network (SAL) with depression severity before treatment, the latter
      accompanied by the increase of white matter in the middle frontal and left
      angular gyri. FNC of aDMN and left frontoparietal network (LFP) decreased after
      treatment. ROI-FC and the brain matter volumes of several regions of DMN, LFP and
      SAL also showed a correlation with ADRS or significant change after treatment.
      LIMITATIONS: Limitations include small sample size and methodological issues
      concerning altered hemodynamics in stroke. However, we took complex preprocessing
      steps to overcome these issues. CONCLUSION: Present results of altered rsFC in
      PSD are consistent with previous findings in MDD. The convergence of results
      obtained in PSD and MDD supports the validity of rsFC approach for investigation
      of brain network dysfunctions underling these psychiatric symptoms.

PMID- 29169126
TI  - Effect of copper on the translocation and transformation of polychlorinated
      biphenyls in rice.
AB  - Contamination of organic pollutants in the environment is usually accompanied by
      heavy metals. However, a little information on the influences of heavy metals on
      the uptake, translocation and transformation of organic pollutants in plants is
      available. In this study, ten-day hydroponic exposure was conducted to explore
      the influence of copper (Cu) on the bioaccumulation and biotransformation of
      polychlorinated biphenyls (PCBs) in intact young rice (Oryza sativa L.). Low dose
      of Cu (<=100 MUmol/L) increased the accumulation of CB-61 in rice plants, while
      excess concentrations of Cu (>100 MUmol/L) inhibited uptake and translocation of
      CB-61. Effect of Cu on the uptake of CB-61 was attributed to the Cu-triggered
      damage to the roots of rice plants. The presence of a moderate dose of Cu (50
      MUmol/L) enhanced the formation of hydroxylated polychlorinated biphenyls (OH
      PCBs) and methoxylated polychlorinated biphenyls (MeO-PCBs), whereas excess
      concentrations of Cu (250 MUmol/L) inhibited the metabolism of CB-61. The effect
      of Cu on the interconversion between 4'-OH-CB-61 and 4'-MeO-CB-61 was also
      concentration dependent: the biotransformation was promoted by a moderate
      concentration of Cu but inhibited by excess concentrations of Cu. The activities
      of Cytochrome P450 (CYP450) and S-adenosyl-l-methionine (SAM)-dependent
      methyltransferase in the roots of rice plants exposed to Cu and CB-61 or its
      derivatives were consistent with the pattern and trend of the metabolites
      observed in rice roots. These results could provide valuable insights into the
      interactions and combined effects of PCBs and heavy metals in plants.

PMID- 29169127
TI  - A decision support tool for selecting the optimal sewage sludge treatment.
AB  - Sewage sludge contains significant amounts of resources, such as nutrients and
      organic matter. At the same time, the organic contaminants (OC) found in sewage
      sludge are of growing concern. Consequently, in many European countries
      incineration is currently favored over recycling in agriculture. This study
      presents a Multi-Attribute Value Theory (MAVT)-based decision support tool (DST)
      for facilitating sludge treatment decisions. Essential decision criteria were
      recognized and prioritized, i.e., weighted, by experts from water utilities.
      Since the fate of organic contaminants was in focus, a simple scoring method was
      developed to take into account their environmental risks. The final DST assigns
      each sludge treatment method a preference score expressing its superiority
      compared to alternative methods. The DST was validated by testing it with data
      from two Finnish municipal wastewater treatment plants (WWTP). The validation
      results of the first case study preferred sludge pyrolysis (preference score:
      0.629) to other alternatives: composting and incineration (score 0.580, and 0.484
      respectively). The preference scores were influenced by WWTP dependent factors,
      i.e., the operating environment and the weighting of the criteria. A lack of data
      emerged as the main practical limitation. Therefore, not all of the relevant
      criteria could be included in the value tree. More data are needed on the effects
      of treatment methods on the availability of nutrients, the quality of organic
      matter and sludge-borne OCs. Despite these shortcomings, the DST proved useful
      and adaptable in decision-making. It can also help achieve a more transparent,
      understandable and comprehensive decision-making process.

PMID- 29169128
TI  - Sample handling and data processing for fluorescent excitation-emission matrix
      (EEM) of dissolved organic matter (DOM).
AB  - In environmental engineering and science, fluorescent excitation-emission matrix
      (EEM) has increasingly been utilized to characterize chromophoric dissolved
      organic matter (CDOM). This study aims to delineate EEM data processing,
      including calculation of total fluorescence (TF) which is an emerging water
      quality parameter often used as a surrogate for micropollutant removal by
      advanced water treatment processes. In addition, sample handling procedures such
      as storage, use of preservatives, and oxidant quenching agents were evaluated. In
      this study, three antimicrobial preservatives were tested: sodium azide, sodium
      omadine, and thymol. All the tested preservatives altered optical properties of
      samples, and were therefore not suitable for the preservation of EEM samples.
      Without preservative, storage of samples at 4  degrees C maintained TF within
      7.5% of its original value for 21 days, while TF of samples stored at the room
      temperature more drastically changed (up to 15%). The impacts of three oxidant
      quenching agents including ascorbic acid, sodium bisulfite, and sodium
      thiosulfate on EEM were also tested. Among the quenching agents, sodium bisulfite
      was found to be suitable since it little influenced optical properties of samples
      while the other two were not favorable due to interference. We also scrutinized
      the use of TF as surrogate to monitor micropollutant rejection by nanofiltration
      membrane.

PMID- 29169129
TI  - Saline soil properties, quality and productivity of wheat grown with bagasse ash
      and thiourea in different climatic zones.
AB  - Soil salinity and atmosphere temperature change have negative impacts on crop
      productivity and its quality and can pose a significant risk to soil properties
      in semi-arid regions. We conducted two field experiments in North (first zone)
      and South (second zone) of Egypt to investigate the effects of soil bagasse ash
      (10 ton ha-1), foliar thiourea (240 g ha-1) and their combination in comparison
      to the control treatment on saline soil properties and productivity and quality
      traits of wheat. All studied treatments were received the recommended rate of N,
      P and K fertilizations. Combination of soil bagasse ash and foliar thiourea
      application resulted in a significant improvement of most studied soil properties
      (i.e. EC, compaction, hydraulic conductivity, OM and available P, K, N contents)
      after harvest in comparison to other treatments in both of zones. Also, it
      enhanced growth and grain yield of wheat in terms of photosynthesis related
      attributes and yield components. Moreover, combination of soil bagasse ash and
      foliar thiourea application resulted in superior grain quality traits in terms of
      carbohydrate, fibre, protein and ash contents than separated application of soil
      bagasse ash, foliar thiourea or even control treatment. In conclusion,
      combination of soil bagasse ash and foliar thiourea application can be used as
      suitable option to enhance plant nutrition, wheat productivity and improve wheat
      grain quality and soil traits in saline soil as well as can alleviate heat
      stress.

PMID- 29169131
TI  - Occurrence of benzothiazole, benzotriazole and benzenesulfonamide derivates in
      outdoor air particulate matter samples and human exposure assessment.
AB  - Benzothiazole (BTHs), benzotriazole (BTRs) and benzenesulfonamide (BSAs)
      derivates are high production volume chemicals and they are used in several
      industrial and household applications, therefore it is expected their occurrence
      in various environments, especially water and air. In this study we developed a
      method based on gas chromatography-mass spectrometry (GC-MS) combined with
      pressurised liquid extraction (PLE) to simultaneously determine four BTR, five
      BTH and six BSA derivates in the particulate matter (PM10) of outdoor air samples
      collected in quartz fibre filters (QFFs). To the best of our knowledge, this is
      the first time these compounds have been determined in open ambient environments.
      Under optimised conditions, method recoveries at the lower and upper
      concentration levels (0.8 and 4.2 ng m-3) ranged from 70 to 120%, except for 1-H
      benzothiazole and 2-chlorobenzothiazole, which were about 50%. The repeatability
      of the method was usually below 20% (n = 3, %RSD) for both concentration levels.
      This method enables the contaminants to be detected at pg m-3 concentration
      levels. Several samples from two different sites influenced by local industries
      showed that BTRs, followed by BTHs, were the most detected compounds, whereas
      BSAs were hardly found. The most frequently determined compounds were 1-H
      benzothiazole, 2-chlorobenzothiazole, 1-H-benzotriazole, 2-hydroxibenzothiazole,
      5,6-dimethyl-1-H-benzotriazole and the isomers 4- and 5-methyl-1-H-benzotriazole.
      With the concentrations found, the human exposure assessment and health risk
      characterization via ambient inhalation were also evaluated taking into account
      different subpopulation groups classified by age for the two sampling points.

PMID- 29169130
TI  - Can liming reduce cadmium (Cd) accumulation in rice (Oryza sativa) in slightly
      acidic soils? A contradictory dynamic equilibrium between Cd uptake capacity of
      roots and Cd immobilisation in soils.
AB  - Cadmium (Cd) accumulation in rice is strongly controlled by liming, but
      information on the use of liming to control Cd accumulation in rice grown in
      slightly acidic soils is inconsistent. Here, pot experiments were carried out to
      investigate the mechanisms of liming on Cd accumulation in two rice varieties
      focusing on two aspects: available/exchangeable Cd content in soils that were
      highly responsive to liming, and Cd uptake and transport capacity in the roots of
      rice in terms of Cd accumulation-relative gene expression. The results showed
      that soil availability and exchangeable iron, manganese, zinc and Cd contents
      decreased with increased liming, and that genes related to Cd uptake (OsNramp5
      and OsIRT1) were sharply up-regulated in the roots of the two rice varieties.
      Thus, iron, manganese, zinc and Cd contents in rice plants increased under low
      liming applications but decreased in response to high liming applications.
      However, yield and rice quantities were only slightly affected. These results
      indicated that Cd accumulation in rice grown in slightly acidic soils presents a
      contradictory dynamic equilibrium between Cd uptake capacity by roots and soil Cd
      immobilisation in response to liming. The enhanced Cd uptake capacity under low
      liming dosages increases risks to human health.

PMID- 29169132
TI  - Comparative evaluation of sorption kinetics and isotherms of pyrene onto
      microplastics.
AB  - Concerns regarding microplastics pollution and their potential to concentrate and
      transport organic contaminants in aquatic environments are growing in recent
      years. Sorption of organic chemicals by microplastics may affect the distribution
      and bioavailability of the chemicals. Here sorption process of pyrene (Pyr), a
      frequently encountered polycyclic aromatic hydrocarbon in aquatic environments,
      on three types of mass-produced plastic particles (high-density polyethylene
      (PE), polystyrene (PS) and polyvinylchloride (PVC)), was investigated by
      comparative analysis of different sorption kinetic and isotherm models. Optimum
      kinetic and isotherm models were predicted by the linear least-squares regression
      method. The pseudo-second-order kinetic model was more appropriate in describing
      the entire sorption process (R2 > 0.99). Sorption rates of Pyr onto microplastics
      were mainly controlled by intraparticle diffusion. PE exhibited the highest
      affinity for Pyr, followed by PS and PVC. The sorption equilibrium data were best
      fitted to the Langmuir isotherm (R2 > 0.99), indicating monolayer coverage of Pyr
      onto the microplastics.

PMID- 29169133
TI  - Alterations of mitochondrial antioxidant indexes and apoptosis in duck livers
      caused by Molybdenum or/and cadmium.
AB  - Cadmium (Cd) and high Molybdenum (Mo) can lead to adverse reactions on animals,
      but the co-induced toxicity of Mo and Cd to liver in ducks was not well
      understood. To investigate the co-induced toxic effects of Mo combined with Cd on
      mitochondrial oxidative stress and apoptosis in duck livers. 240 healthy 11-day
      old ducks were randomly divided into 6 groups (control, LMo group, HMo group, Cd
      group, LMoCd group and HMoCd group). After being treated for 30, 60, 90 and 120
      days, liver mitochondrial antioxidant indexes, ceruloplasmin (CP),
      metallothionein (MT), Bak-1 and Caspase-3 genes mRNA expression levels, and
      ultrastructural changes were evaluated. The results showed that total
      antioxidative capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and
      xanthine oxidase (XOD) activities in experimental groups were decreased, whereas
      malondialdehyde (MDA) content and nitric oxide synthase (NOS) activity were
      increased compared with control group, and these changes of co-treated groups
      were more obvious in the later period of the experiment. The mRNA expression
      levels of CP, Bak-1 and Caspase-3 were up-regulated in experimental groups
      compared with control group and showed significant difference between co-treated
      groups and single treated groups. The mRNA expression level of MT in Cd group was
      higher than that in co-treated groups. Additionally, ultrastructural changes
      showed karyopyknosis, mitochondrial swelling, vacuolation and disruption of
      mitochondrial cristae in co-treated groups. Taken together, it was suggested that
      dietary Mo and Cd might lead to mitochondrial oxidative stress and apoptosis in
      duck livers, and it showed a possible synergistic relationship between the two
      elements.

PMID- 29169134
TI  - The comparison of greenhouse gas emissions in sewage treatment plants with
      different treatment processes.
AB  - Greenhouse gas emissions from different sewage treatment plants: oxidation ditch
      process, double-circulated anoxic-oxic process and anoxic-oxic process were
      evaluated based on the survey. The methane and nitrous oxide characteristics were
      discussed based on the gaseous and dissolved gas profiles. As a result, it was
      found that methane was produced in the sewer pipes and the primary sedimentation
      tank. Additionally, a ventilation system would promote the gasification of
      dissolved methane in the first treatment units. Nitrous oxide was produced and
      emitted in oxic tanks with nitrite accumulation inside the sewage treatment
      plant. A certain amount of nitrous oxide was also discharged as dissolved gas
      through the effluent water. If the amount of dissolved nitrous oxide discharge is
      not included, 7-14% of total nitrous oxide emission would be overlooked. Based on
      the greenhouse gas calculation, electrical consumption and the N2O emission from
      incineration process were major sources in all the plants. For greenhouse gas
      reduction, oxidation ditch process has an advantage over the other advanced
      systems due to lower energy consumption, sludge production, and nitrogen removal
      without gas stripping.

PMID- 29169135
TI  - Nitrogen removal capacity and bacterial community dynamics of a Canon biofilter
      system at different organic matter concentrations.
AB  - Three Canon bench-scale bioreactors with a volume of 2 L operating in parallel
      were configured as submerged biofilters. In the present study we investigated the
      effects of a high ammonium concentration (320 mgNH4+. L-1) and different
      concentrations of organic matter (0, 100 and 400 mgCOD.L-1) on the nitrogen
      removal capacity and the bacterial community structure. After 60 days, the Canon
      biofilters operated properly under concentrations of 0 and 100 mgCOD.L-1 of
      organic matter, with nitrogen removal efficiencies up to 85%. However, a higher
      concentration of organic matter (400 mgCOD.L-1) produced a partial inhibition of
      nitrogen removal (68.1% efficiency). The addition of higher concentrations of
      organic matter a modified the bacterial community structure in the Canon
      biofilter, increasing the proliferation of heterotrophic bacteria related to the
      genera of Thauera, Longilinea, Ornatilinea, Thermomarinilinea, unclassified
      Chlorobiales and Denitratisoma. However, heterotrophic bacteria co-exist with
      Nitrosomonas and Candidatus Scalindua. Thus, our study confirms the co-existence
      of different microbial activities (AOB, Anammox and denitrification) and the
      adaptation of a fixed-biofilm system to different concentrations of organic
      matter.

PMID- 29169136
TI  - Degradation of diethyl phthalate (DEP) by UV/persulfate: An experiment and
      simulation study of contributions by hydroxyl and sulfate radicals.
AB  - Degradation of diethyl phthalate (DEP) by ultraviolet/persulfate (UV/PS) process
      at different reaction conditions was evaluated. DEP can be degraded effectively
      via this process. Both tert-butyl (TBA) and methanol (MeOH) inhibited the
      degradation of DEP with MeOH having a stronger impact than TBA, suggesting
      sulfate radical () and hydroxyl radical (HO) both existed in the reaction systems
      studied. The second-order rate constants of DEP reacting with and HO were
      calculated to be (6.4+/-0.3)*107 M-1s-1 and (3.7+/-0.1)*109 M-1s-1, respectively.
      To further access the potential degradation mechanism in this system, the pseudo
      first-order rate constants (ko) and the radical contributions were modeled using
      a simple steady-state kinetic model involving and HO. Generally, HO had a greater
      contribution to DEP degradation than . The ko of DEP increased as PS dosages
      increased when PS dosages were below 1.9 mM. However, it decreased with
      increasing initial DEP concentrations, which might be due to the radical
      scavenging effect of DEP. The ko values in acidic conditions were higher than
      those in alkaline solutions, which was probably caused by the increasing
      concentration of hydrogen phosphate (with higher scavenging effects than
      dihydrogen phosphate) from the phosphate buffer as pH values rose. Natural
      organic matter and bicarbonate dramatically suppressed the degradation of DEP by
      scavenging and HO. Additionally, the presence of chloride ion (Cl-) promoted the
      degradation of DEP at low Cl- concentrations (0.25-1 mM). Finally, the proposed
      degradation pathways were illustrated.

PMID- 29169137
TI  - Characterization and mechanism analysis of lincomycin biodegradation with
      Clostridium sp. strain LCM-B isolated from lincomycin mycelial residue (LMR).
AB  - Lincomycin mycelial residue (LMR) is the restricted resource because it contains
      residual lincomycin, which is producing potential risks to the environment and
      human health. In this study, lincomycin-degrading strain LCM-B was isolated and
      identified as Clostridium sp. in the LMR. Strain LCM-B was able to degrade 62.03%
      of lincomycin at the initial concentration of 100 mg L-1 after incubation for 10
      d, while only 15.61% of lincomycin was removed at the initial concentration of
      500 mg L-1. The removal efficiency of lincomycin by strain LCM-B decreased as the
      initial concentration increased. Gene lnuB (which encodes the nucleotidyl
      transferase) was detected in the isolated strain, and it was proven to
      participate in lincomycin biodegradation based on the analysis of degradation
      products and pathway. The results provide a relatively complete understanding of
      lincomycin biodegradation mechanism. Strain LCM-B is promising to eliminate
      lincomycin from the LMR.

PMID- 29169138
TI  - In situ fabrication of green reduced graphene-based biocompatible anode for
      efficient energy recycle.
AB  - Improving the anode configuration to enhance biocompatibility and accelerate
      electron shuttling is critical for efficient energy recovery in microbial fuel
      cells (MFCs). In this paper, green reduced graphene nanocomposite was
      successfully coated using layer-by-layer assembly technique onto carbon brush
      anode. The modified anode achieved a 3.2-fold higher power density of 33.7 W m-3
      at a current density of 69.4 A m-3 with a 75% shorter start period. As revealed
      in the characterization, the green synthesized nanocomposite film affords larger
      surface roughness for microbial colonization. Besides, gold nanoparticles, which
      anchored on graphene sheets, promise the relatively high electroactive sites and
      facilitate electron transfer from electricigens to the anode. The reduction
      oxidation peaks in cyclic voltammograms indicated the mechanism of surface
      cytochromes facilitated current generation while the electrochemical impedance
      spectroscopy confirmed the enhanced electron transfer from surface cytochrome to
      electrode. The green synthesis process has the potential to generate a high
      performing anode in further applications of MFCs.

PMID- 29169139
TI  - Analysis of extracellular polymeric substances (EPS) and ciprofloxacin-degrading
      microbial community in the combined Fe-C micro-electrolysis-UBAF process for the
      elimination of high-level ciprofloxacin.
AB  - Extracellular polymeric substances (EPS) and ciprofloxacin-degrading microbial
      community in the combined Fe-C micro-electrolysis and up-flow biological aerated
      filter (UBAF) process for the treatment of high-level ciprofloxacin (CIP) were
      analyzed. The research demonstrated a great potential of Fe-C micro-electrolysis
      UBAF for the elimination of high-level CIP. Above 90% of CIP removal was achieved
      through the combined process at 100 mg L-1 of CIP loading. In UBAF, the
      pollutants were mainly removed at 0-70 cm heights. Three-dimensional fluorescence
      spectrum (3D-EEM) was used to characterize the chemical structural of loosely
      bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) extracted from biofilm sample
      in UBAF. The results showed that the protein-like substances in LB-EPS and TB-EPS
      had no clear change in the study. Nevertheless, an obvious release of
      polysaccharides in EPSs was observed during long-term exposure to CIP, which was
      considered as a protective response of microbial to CIP toxic. The high
      throughput sequencing results revealed that the biodiversity of bacteria
      community became increasingly rich with gradual ciprofloxacin biodegradation in
      UBAF. The ciprofloxacin-degrading microbial community was mainly dominated by
      Proteobacteria and Bacteroidetes. Microorganisms from genera Dechloromonas,
      Brevundimonas, Flavobacterium, Sphingopyxis and Bosea might take a major role in
      ciprofloxacin degradation. This study provides deep theoretical guidance for real
      CIP wastewater treatment.

PMID- 29169141
TI  - Complicated grief and caregiving correlates among bereaved adolescent girls in
      South Africa.
AB  - To our knowledge, this is the first study to document correlates of complicated
      grief among bereaved adolescents in sub-Saharan Africa. Participants included 339
      female adolescents in South Africa who experienced the loss of a loved one at
      least six months prior to the survey; their primary caregivers were also
      surveyed. One-fifth of adolescents were classified as having complicated grief
      using the Inventory of Complicated Grief Revised for Children in conjunction with
      grief-induced functional impairment. The loss of a biological parent, the primary
      caregiver's level of grief, and economic stressors since the loss were associated
      with increased odds of complicated grief among adolescents. Adolescents' age,
      residential changes, time since the loss, multiple losses, bereavement due to
      death by illness, and caregiver depression did not affect the odds. Findings
      signal the potential of family-centered interventions and economic support
      services for bereaved adolescents.

PMID- 29169140
TI  - Facile green synthesis of zinc oxide nanoparticles using Ulva lactuca seaweed
      extract and evaluation of their photocatalytic, antibiofilm and insecticidal
      activity.
AB  - The bioactivity of semiconductor nanocomplexes has been poorly studied in the
      field of pesticide science. In this research, the synthesis of zinc nanoparticles
      was accomplished through new effortless green chemistry process, using the Ulva
      lactuca seaweed extract as a reducing and capping agent. The production of U.
      lactuca-fabricated ZnO nanoparticles (Ul-ZnO Nps) was characterized by powder X
      ray diffraction (XRD), UV-visible, Fourier transform infrared (FTIR)
      spectroscopy, selected area electron diffraction (SAED) analysis and transmission
      electron microscopy (TEM). The U. lactuca-fabricated ZnO NPs were tested for
      their photodegradative action against organic dyes, as well as for antibiofilm
      and larvicidal activities. The UV visible absorbance spectrum of Ul-ZnO NPs
      exhibited the absorbance band at 325nm and TEM highlighted average crystallite
      sizes of nanoparticles of 10-50nm. Methylene blue (MB) dye was efficiently
      corrupted under sunlight in presence of Ul-ZnO NPs. Excellent bactericidal
      activity was shown by the Ul-ZnO Nps on Gram positive (Bacillus licheniformis and
      Bacillus pumilis) and Gram negative (Escherichia coliand Proteus vulgaris)
      bacteria. High antibiofilm potential was noted under both dark and sunlight
      conditions. The impact of a single treatment with Ul-ZnO NPs on biofilm
      architecture was also analyzed by confocal laser scanning microscopy (CLSM) on
      both Gram positive and Gram negative bacteria. Moreover, Ul-ZnO NPs led to 100%
      mortality of Aedes aegypti fourth instar larvae at the concentration of 50MUg/ml
      within 24h. The effects of ZnO nanoparticle-based treatment on mosquito larval
      morphology and histology were monitored. Overall, based on our results, we
      believe that the synthesis of multifunctional Ul-ZnO Nps using widely available
      seaweed products can be promoted as a potential eco-friendly option to chemical
      methods currently used for nanosynthesis of antimicrobials and insecticides.

PMID- 29169142
TI  - A matter of fact? Adolescents' assumptions about crime, laws, and authority and
      their domain-specific beliefs about punishment.
AB  - This study examined adolescents' beliefs about the amount of punishment
      individuals should receive for violating different laws and whether these beliefs
      are connected with their informational assumptions (i.e., perceived facts) about
      crime, laws, and authority. American adolescents (N = 340; Mage = 16.64, 58.2%
      female) reported their judgments concerning the appropriate punishment for
      violating laws regulating domain-specific behaviors and their informational
      assumptions regarding the prevalence and causes of crime, beliefs that authority
      is knowledgeable, and the purpose of punishment. Greater internal attributions
      for crime was associated with stronger punishment judgments for violating laws
      that regulate moral and conventional issues. Greater beliefs that punishment
      teaches right from wrong was associated with stronger punishment judgments for
      violating laws that regulate drug-related prudential issues, and lower punishment
      judgments for violating laws that regulate personal issues. Greater beliefs that
      authorities are more knowledgeable than others was associated with stronger
      punishment judgments for violating laws that regulate personal issues.

PMID- 29169143
TI  - Energy dissipation mapping of cancer cells.
AB  - The purpose of this study is to map the energy dissipation of Jurkat cells using
      a single 60 nanosecond pulse electric field (NsPEF), primarily through atomic
      force microscopy (AFM). The phase shift is generated by the sample elements that
      do not have a heterogeneous surface. Monitoring and manipulating the phase shift
      is a powerful way for determining the dissipated energy and plotting the
      topography. The dissipated energy is a relative value, so the silica wafer and
      cover slip are given a set reference while the transmission of energy between the
      tip of the cantilever and cell surfaces is measured. The most important finding
      is that the magnitude and the number of variations in the dissipated energy
      change with the strength of NsPEF applied. Utilizing a single low field strength
      NsPEF (15kV/cm), minor changes in dissipated energy were found. The application
      of a single high field strength NsPEF (60kV/cm) to Jurkat cells resulted in a
      higher dissipated energy change versus that of in the low field strength
      condition. Thus, the dissipated energy from the Jurkat cells changes with the
      strength of NsPEF. By analyzing the forces via investigation in the tapping mode
      of the AFM, the stabilization of the cytoskeleton and membrane of the cell are
      related to the strength of NsPEF applied. Furthermore, the strength of NsPEF
      indicates a meaningful relationship to the survival of the Jurkat cells.

PMID- 29169145
TI  - Early results on canine fetal kidney development: Ultrasonographic evaluation and
      value in prediction of delivery time.
AB  - To date there have been no studies that describe the ultrasonographic evaluation
      of kidney development in canine fetuses. The aim of this prospective and
      longitudinal study was to monitor fetal kidney development with ultrasound and
      use fetal kidney measurements as a complementary biometric index for estimation
      of gestational age. Ultrasonographic examinations were performed on 15 clinically
      healthy pregnant bitches every four days from 30th day of pregnancy, until
      visualization of the fetal renal pelvis was no longer possible. Four distinct
      periods of ultrasonographic canine fetal kidney development were defined. Kidney
      length and renal pelvis distention were measured on longitudinal plane images.
      The fetal kidney ranged from 0.40 cm to 2.30 cm in length, and diameter of the
      pelvis ranged from 0.06 cm to 0.17 cm, however by the end of gestation the renal
      pelvis was no longer dilated and so its diameter could not be measured.
      Statistical analysis confirmed a relationship between gestational age and fetal
      kidney growth. Ultrasonographic evaluation of fetal kidney development is simple
      to perform. There is a strong correlation between gestational age and kidney
      length, which allowed generation of an equation to estimate delivery date with
      high sensitivity between 48 and 52 days of pregnancy. Fetal organ development can
      be considered complete when the renal pelvis is no longer dilated, this finding
      can assist the ultrasonographer in staging the gestation by prompting examination
      for fetal intestinal motility which begins at the same gestational age.
      Measurement of fetal kidney length can be used in conjunction with other methods
      to estimate gestational age and predict delivery time.

PMID- 29169144
TI  - Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and
      inhibitors.
AB  - The Wnt/beta-catenin pathway is a family of proteins that is implicated in many
      vital cellular functions such as stem cell regeneration and organogenesis.
      Several intra-cellular signal transduction pathways are induced by Wnt, notably
      the Wnt/beta-catenin dependent pathway or canonical pathway and the non-canonical
      or beta-catenin-independent pathway; the latter includes the Wnt/Ca2+ and Planar
      Cell Polarity pathway (PCP). Wnt activation occurs at the intestinal crypt floor,
      and is critical to optimal maintenance of stem cells. Colorectal cancers show
      evidence of Wnt signaling pathway activation and this is associated with loss of
      function of the tumor regulator APC. Wnt activation has been observed in breast,
      lung, and hematopoietic malignancies and contributes to tumor recurrence. The Wnt
      pathway cross talks with the Notch and Sonic Hedgehog pathways, which has
      implications for therapeutic interventions in cancers. There are significant
      challenges in targeting the Wnt pathway, including finding agents that are
      efficacious without damaging the system of normal somatic stem cell function in
      cellular repair and tissue homeostasis. Here, we comprehensively review the Wnt
      pathway and its interactions with the Notch and Sonic Hedgehog pathways. We
      present the state of the field in effectors and inhibitors of Wnt signaling,
      including updates on clinical trials in various cancers with inhibitors of Wnt,
      Notch, and Sonic Hedgehog.

PMID- 29169147
TI  - C-type lectin receptors in anti-fungal immunity.
AB  - Host immune systems are constantly engaged with fungal pathogens which are common
      in environments as well as in healthy human skin and mucosa. C-type lectin
      receptors (CLRs) are expressed in myeloid cells and play central roles in host
      defenses against fungal infections by coordinating innate and adaptive immune
      systems. Upon ligand binding, CLRs stimulate cellular responses by inducing the
      production of cytokines and reactive oxygen species via the Syk/CARD9 signaling
      pathway, leading to fungal elimination. Due to identification and
      characterization of the CLRs, the underlying mechanisms of the anti-fungal
      immunity are being unveiled in the present decade. In this review, we focus on
      the anti-fungal activities of CLRs and summarize of current knowledge of the
      related expression profiles, modes of ligand recognition, and signaling cascades.

PMID- 29169146
TI  - How bacteria control the CRISPR-Cas arsenal.
AB  - CRISPR-Cas systems are adaptive immune systems that protect their hosts from
      predation by bacteriophages (phages) and parasitism by other mobile genetic
      elements (MGEs). Given the potent nuclease activity of CRISPR effectors, these
      enzymes must be carefully regulated to minimize toxicity and maximize anti-phage
      immunity. While attention has been given to the transcriptional regulation of
      these systems (reviewed in [1]), less consideration has been given to the crucial
      post-translational processes that govern enzyme activation and inactivation.
      Here, we review recent findings that describe how Cas nucleases are controlled in
      diverse systems to provide a robust anti-viral response while limiting auto
      immunity. We also draw comparisons to a distinct bacterial immune system,
      restriction-modification.

PMID- 29169148
TI  - Selenite-induced nitro-oxidative stress processes in Arabidopsis thaliana and
      Brassica juncea.
AB  - Extremes of selenium (Se) exert toxic effects on plants' physiological processes;
      although plant species tolerate Se differently. This study focuses on the effect
      of Se (0, 20, 50 or 100MUM sodium selenite) on secondary nitro-oxidative stress
      processes mainly using in situ microscopic methods in non-accumulator Arabidopsis
      thaliana and secondary Se accumulator Brassica juncea. Relative Se tolerance or
      sensitivity of the species was evaluated based on growth parameters (fresh and
      dry weight, root growth) and cell viability. Besides, selenite-triggered cell
      wall modifications (pectin, callose) and stomatal regulations were determined for
      the first time. In case of Arabidopsis, relative selenite sensitivity was
      accompanied by decreased stomatal density and induced stomatal opening, callose
      accumulation, pronounced oxidative stress and moderate nitrosative modifications.
      In contrast, the selenite-treated, relatively tolerant Brassica juncea showed
      larger number of more opened stomata, pectin accumulation, moderate oxidative and
      intense nitrosative stress. These suggest that selenite tolerance or sensitivity
      is rather associated with oxidative processes than secondary nitrosative
      modifications in higher plants.

PMID- 29169149
TI  - Prokaryotic Expression and Anti-IBDV Activity of Chicken Interleukin-18 and
      Interferon-gamma.
AB  - Interferon-gamma (IFN-gamma), a cytokine produced by activated natural killer
      cells and T lymphocytes, is an important regulator of innate and adaptive
      immunity. Interleukin (IL)-18, also known as IFN-gamma-inducing factor, is a
      cytokine that induces T and natural killer cells to produce IFN-gamma. In this
      study, the chicken IL-18 (ChIL-18) and chicken IFN-gamma (ChIFN-gamma) genes were
      inserted into the pET28a prokaryotic expression vector, resulting in pET28a-IL-18
      and pET28a-IFN-gamma, respectively. These plasmids were transformed into
      Escherichia coli strain BL21, and the ChIL-18 and ChIFN-gamma proteins were
      expressed and purified. To determine their antiviral activities, 200 ng/mL of
      ChIL-18 and/or ChIFN-gamma were inoculated into chicken embryonic fibroblast
      cells. After 24 h, one 50% tissue culture infective dose (TCID50) of infectious
      bursal disease virus (IBDV) was inoculated into the chicken embryonic fibroblast
      cells. The results showed that the antiviral effect of ChIL-18 and ChIFN-gamma in
      combination was better than that of ChIL-18 or ChIFN-gamma alone. Next, 14-day
      old chicken were injected with 200 ug of ChIL-18 and/or ChIFN-gamma and then were
      challenged with 103 TCID50 of IBDV via intraperitoneal injection. The results
      showed that the proliferation of IBDV was inhibited by the injection of the
      recombinant proteins, especially the combination of ChIL-18 and ChIFN-gamma, as
      evidenced by cytokine detection, quantitative PCR, and pathology analyses. These
      results indicate that ChIL-18 and ChIFN-gamma could inhibit IBDV infection and
      the combination of ChIL-18 and ChIFN-gamma has a better inhibitory effect than
      either cytokine alone.

PMID- 29169150
TI  - Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular
      Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
      death worldwide, and prognosis remains unsatisfactory since the disease is often
      diagnosed at the advanced stages. Currently, the multikinase inhibitor sorafenib
      is the only drug approved for the treatment of advanced HCC. However, primary or
      acquired resistance to sorafenib develops, generating a roadblock in HCC therapy.
      Autophagy is an intracellular lysosomal pathway involved in protein and organelle
      degradation, with an astonishing number of connections to human disease and
      physiology. Current understanding of the role of autophagy in the progression of
      cancer and the response to cancer therapy remains controversial. Sorafenib is
      able to induce autophagy in HCC, but the effect of autophagy is indistinct. Some
      studies established that sorafenib-induced autophagy serves as a pro-survival
      response. However, other studies found that sorafenib-induced autophagy improves
      the lethality of sorafenib against HCC cells. The mechanisms underlying autophagy
      and sorafenib resistance remain elusive. The purpose of this review is to
      summarize the progress of research focused on autophagy and sorafenib resistance
      and to update current knowledge of how cellular autophagy impacts sorafenib
      sensitivity in HCC treatment.

PMID- 29169151
TI  - Cystic Lung Disease in Genetic Syndromes with Deficient Tumor Suppressor Gene
      Function.
AB  - Cystic lung diseases constitute a distinct group of rare lung disorders, among
      which two result from monogenic defects affecting tumor suppressor genes:
      lymphangioleiomyomatosis, either sporadic or associated with tuberous sclerosis
      complex, and Birt-Hogg-Dube syndrome. These disorders have similarities in their
      clinical expression, including occurrence in young adults, multiple pulmonary
      cysts, recurrent pneumothorax, skin hamartomas, and renal tumors. However, they
      markedly differ in their gender distribution, pathogenesis, disease course, and
      prognosis. Our knowledge on these two rare conditions is rapidly expanding.
      Management of lymphangioleiomyomatosis has substantially improved in the past
      decade with the understanding of its pathogenic mechanisms, the discovery of an
      effective therapy, and development of large cohorts and international guidelines.
      Birt-Hogg-Dube syndrome has been described more recently and still awaits deeper
      understanding of its pathophysiology.

PMID- 29169152
TI  - Knockdown of CAVEOLIN-1 Sensitizes Human Basal-Like Triple-Negative Breast Cancer
      Cells to Radiation.
AB  - BACKGROUND/AIMS: Triple-negative breast cancer (TNBC) is a high-risk breast
      cancer phenotype without specific targeted therapy options and is significantly
      associated with increased local recurrence in patients treated with radiotherapy.
      CAVEOLIN-1 (CAV-1)-mediated epidermal growth factor receptor (EGFR) nuclear
      translocation following irradiation promotes DNA repair and thus induces
      radiation resistance. In this study, we aimed to determine whether knockdown of
      CAV-1 enhances the radiosensitivity of basal-like TNBC cell lines and to explore
      the possible mechanisms. METHODS: Western blotting was used to compare protein
      expression in a panel of breast cancer cell lines. Nuclear accumulation of EGFR
      as well as DNA repair and damage at multiple time points following irradiation
      with or without CAV-1 siRNA pretreatment were investigated using western blotting
      and confocal microscopy. The radiosensitizing effect of CAV-1 siRNA was evaluated
      using a clonogenic assay. Flowcytometry was performed to analyse cell apoptosis
      and cell cycle alteration. RESULTS: We found that CAV-1 is over-expressed in
      basal-like TNBC cell lines and barely expressed in HER-2-positive cells;
      additionally, we observed that HER-2-positive cell lines are more sensitive to
      irradiation than basal-like TNBC cells. Our findings revealed that radiation
      induced EGFR nuclear translocation was impaired by knockdown of CAV-1. In
      parallel, radiation-induced elevation of DNA repair proteins was also hampered by
      pretreatment with CAV-1 siRNA before irradiation. Silencing of CAV-1 also
      promoted DNA damage 24 h after irradiation. Colony formation assays verified that
      cells could be radiosensitized after knockdown of CAV-1. Furthermore, G2/M cell
      cycle arrest and apoptosis enhancement may also contribute to the
      radiosensitizing effect of CAV-1 siRNA. CONCLUSION: Our results support the
      hypothesis that CAV-1 knockdown by siRNA causes increased radiosensitivity in
      basal-like TNBC cells. The mechanisms associated with this effect are reduced DNA
      repair through delayed CAV-1-associated EGFR nuclear accumulation and induction
      of G2/M arrest and apoptosis through the combined effects of CAV-1 siRNA and
      radiation.

PMID- 29169153
TI  - Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with
      Hematological Malignancy.
AB  - BACKGROUND: Teicoplanin is a glycopeptide antibiotic currently used for the
      treatment of methicillin-resistant Staphylococcus aureus. The need for
      therapeutic drug monitoring of teicoplanin has been increasingly highlighted as
      important. It is generally accepted that whereas a plasma trough concentration
      (Cmin) of >=10 mg/L is appropriate for the majority of infections, it should
      exceed 20 mg/L for severe infections. The target Cmin of teicoplanin in patients
      with febrile neutropenia (FN) has not been reported. The aim of this study was to
      estimate the target Cmin for the treatment of FN in patients with hematological
      malignancy. METHODS: In this retrospective, single-center, observational cohort
      study, the records of 52 hospitalized patients with hematological malignancy who
      were treated with teicoplanin for FN due to bacteriologically documented or
      presumptive gram-positive infections were analyzed. RESULTS: A significant
      difference in the first Cmin of teicoplanin was observed between the response and
      nonresponse groups in patients with bacteremia. The areas under the receiver
      operating characteristic curves were 0.80 for clinical efficacy. The cut-off
      value of teicoplanin Cmin on days 4-6 was 15.2 mg/L (sensitivity 80.0%,
      specificity 75.0%). CONCLUSIONS: The authors propose a target teicoplanin Cmin of
      >=15.2 mg/L for FN in patients with hematological malignancy.

PMID- 29169154
TI  - Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of
      Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with
      Aflibercept.
AB  - PURPOSE: To evaluate the development of neovascular age-related macular
      degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by
      a treat-and-extend (TAE) regimen with intravitreal aflibercept injections.
      METHODS: We retrospectively studied 104 patients with treatment-naive unilateral
      nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in
      the treated eyes and development of nAMD in the fellow eye for 2 years. RESULTS:
      The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal
      choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation
      (RAP). BCVA was significantly improved after the loading phase in all subtypes.
      Forty-six patients (44.2%) had no recurrence within 2 years after the loading
      phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with
      RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2
      years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p <
      0.001). CONCLUSIONS: Patients with RAP had significantly more frequent
      development of nAMD in the fellow eye compared to other subtypes, while they
      showed significantly less recurrence during the TAE regimen with intravitreal
      aflibercept injections. Development of nAMD in the fellow eye should be monitored
      in RAP when the injection interval is extended.

PMID- 29169156
TI  - Folliculotropism Does Not Affect Overall Survival in Mycosis Fungoides: Results
      from a Single-Center Cohort and Meta-Analysis.
AB  - BACKGROUND: Folliculotropic mycosis fungoides (FMF) is a distinct subtype of
      mycosis fungoides (MF) with unique clinicopathological features. The medical
      literature suggests that FMF has a more aggressive course and worse survival than
      classic MF. Previous studies do not use standardized treatment, and no studies
      have reported an association between treatment response and overall survival
      (OS). OBJECTIVE: To compare OS for MF, FMF, and Sezary syndrome (SS) patients.
      METHODS: Data were collected retrospectively from 218 patients (171 MF, 15 SS, 32
      FMF) treated in a single academic center between 1970 and 2016. RESULTS: Negative
      predictors of OS were age (OR = 1.07), male sex (OR = 1.63), and stage IIB, III,
      and IV (OR = 4.10, 5.42, and 7.54, respectively, vs. stage IA). Lack of initial
      PUVA response was strongly associated with negative OS (OR = 3.08). Kaplan-Meier
      analysis of age-, sex-, and stage-matched MF and FMF patients found similar OS
      between the 2 groups. The 5-year OS was 91% for FMF and 74% for MF. Meta-analysis
      of current data and 2 published studies where survival of FMF patients was
      compared to MF did not reveal statistically significant differences between these
      2 diseases. CONCLUSIONS: When patients were matched for age, sex, and disease
      stage, folliculotropism did not affect OS in MF.

PMID- 29169155
TI  - Rho Kinase Regulates Aortic Vascular Smooth Muscle Cell Stiffness Via
      Actin/SRF/Myocardin in Hypertension.
AB  - BACKGROUND/AIMS: Our previous studies demonstrated that intrinsic aortic smooth
      muscle cell (VSMC) stiffening plays a pivotal role in aortic stiffening in aging
      and hypertension. However, the underlying molecular mechanisms remain largely
      unknown. We here hypothesized that Rho kinase (ROCK) acts as a novel mediator
      that regulates intrinsic VSMC mechanical properties through the serum response
      factor (SRF) /myocardin pathway and consequently regulates aortic stiffness and
      blood pressure in hypertension. METHODS: Four-month old male spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were studied. Aortic
      stiffness was measured by echography. Intrinsic mechanical properties of VSMCs
      were measured by atomic force microscopy (AFM) in vitro. RESULTS: Compared to WKY
      rats, SHR showed a significant increase in aortic stiffness and blood pressure,
      which is accompanied by a remarkable cell stiffening and ROCK activation in
      thoracic aortic (TA) VSMCs. Theses alterations in SHR were abolished by Y-27632,
      a specific inhibitor of ROCK. Additionally, boosted filamentous/globular actin
      ratio was detected in TA VSMCs from SHR versus WKY rats, resulting in an up
      regulation of SRF and myocardin expression and its downstream stiffness
      associated genes including alpha-smooth muscle actin, SM22, smoothelin and myosin
      heavy chain 11. Reciprocally, these alterations in SHR TA VSMCs were also
      suppressed by Y-27632. Furthermore, a specific inhibitor of SRF/myocardin, CCG
      100602, showed a similar effect to Y-27632 in SHR in both TA VSMCs stiffness in
      vitro and aorta wall stiffness in vivo. CONCLUSION: ROCK is a novel mediator
      modulating aortic VSMC stiffness through SRF/myocardin signaling which offers a
      therapeutic target to reduce aortic stiffening in hypertension.

PMID- 29169157
TI  - TNF-alpha Regulates Mast Cell Functions by Inhibiting Cell Degranulation.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the involvement of
      inducible co-stimulatory ligand (ICOSL) expression in stimulation of mast cells
      (MCs) by TNF-alpha and the ability of TNF-alpha stimulation of MCs to influence
      CD4+ T cell differentiation and function. The mechanisms underlying TNF-alpha
      stimulation of MCs were also explored. METHODS: Mast cells and CD4+ T cells were
      prepared from C57BL/6 mice (aged 6-8 weeks). ICOSL expression by MCs was measured
      by real-time PCR and flow cytometry, and levels of IL-4, IL-10 and IFN-gamma were
      measured by ELISA. RESULTS: ICOSL expression by MCs was increased by TNF-alpha
      stimulation, and resulted in interaction with CD4+ T cells. The IL-4 and IL-10
      levels in the co-culture system increased, while IFN-gamma levels decreased.
      Furthermore, CD4+CD25+Foxp3+ T cell proliferation was induced by co-culture with
      TNF-alpha-stimulated MCs. The mechanism by which TNF-alpha stimulated MCs was
      dependent on the activation of the MAPK signaling pathway. CONCLUSION: TNF-alpha
      upregulated the expression of ICOSL on mast cells via a mechanism that is
      dependent on MAPK phosphorylation. TNF-alpha-treated MCs promoted the
      differentiation of regulatory T cells and induced a shift in cytokine expression
      from a Th1 to a Th2 profile by up-regulation ICOSL expression and inhibition of
      MC degranulation. Our study reveals a novel mechanism by which mast cells
      regulate T cell function.

PMID- 29169158
TI  - Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive
      Tract.
AB  - BACKGROUND/AIMS: MicroRNAs participate in various biological processes in
      malignant tumors. However, the mechanisms of miR-224-5p in digestive system
      cancers are not fully understood. A comprehensive investigation of the clinical
      value and potential targets of miR-224-5p in cancers of the digestive tract is
      necessary. METHODS: Expression profiling data and related-prognostic data of miR
      224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas,
      ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p
      were predicted using bioinformatics methods and finally annotated using Gene
      Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathway enrichment analysis. RESULTS: MiR-224-5p is up-regulated in digestive
      system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate
      diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that
      miR-224-5p is statistically significantly correlated with overall survival
      univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate
      analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224
      5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis
      revealed that the top terms of miR-224-5p in biological process, cellular
      component and molecular function were system development, neuron part, and
      transcriptional activator activity, RNA polymerase II core promoter proximal
      region sequence-specific binding, respectively. Moreover, eight pathways were
      identified in KEGG pathway enrichment analysis. CONCLUSIONS: MiR-224-5p is up
      regulated and has the potential to become a diagnostic and prognostic biomarker
      in digestive system cancers. MiR-224-5p might play vital roles in cancers of the
      digestive tract but the exact molecular mechanisms need further study and
      verification.

PMID- 29169159
TI  - An Unexpected Lesson in Global Nephrology.

PMID- 29169160
TI  - The Use of Peritoneal Dialysis in Phenobarbitone Toxicity in a Critically Unwell
      Neonate.
AB  - BACKGROUND: Phenobarbitone (PB) is the first-line anti-convulsant for neonatal
      seizures. The use of peritoneal dialysis (PD) to enhance drug elimination in
      cases of neonatal PB overdose has not been reported. OBJECTIVE: To report a case
      of neonatal severe PB toxicity and review the elimination of PB by PD. METHODS:
      Assessment of PD drug clearance. RESULTS: A neonate with prolonged seizures was
      administered PB. Encephalopathy and myocardial failure developed, which were
      initially suspected to be secondary to hypoxia. At 42 h of age, the serum PB
      concentration was in the toxic range at 131 mg/L. Despite supportive care, the
      infant's condition deteriorated with escalating inotropes and the need for CPR.
      Enhanced PB elimination via multiple-dose activated charcoal and exchange
      transfusion were considered too risky. Hourly PD cycles via Tenckhoff catheter
      were commenced, based on reports suggesting that PD enhances PB clearance. The
      clinical state of the infant then improved. PD administration was continued for
      60 h, recovering 20% of the estimated total PB body load. The infant survived and
      there were no PD complications. CONCLUSIONS: PD increased PB clearance in this
      neonate, correlating with clinical recovery. Where other techniques are not
      possible, PD may have a role to play in enhancing PB elimination.

PMID- 29169161
TI  - Digoxin and Hypermagnesuria.
AB  - In a recent issue of Nephron, Abu-Amer et al.[<xref ref-type="bibr"
      rid="ref1">1</xref>] reported the presence of hypermagnesuria in patients
      following acute intravenous administration of digoxin and suggested that the
      Na+/K+-ATPase gamma-subunit, which is the pharmacological target of digoxin, can
      play a role in this process. Hypermagnesuria induced by digoxin may have
      important clinical consequences, particularly in the presence of inherited and
      acquired conditions associated with hypermagnesuria and hypomagnesemia. Moreover,
      the co-administration of digoxin with other drugs that reduce gastrointestinal
      absorption (i.e., proton pump inhibitors) or increase urinary excretion (i.e.,
      loop diuretics) may increase the likelihood of developing hypomagnesemia. In this
      article, we reviewed the main causes of hypermagnesuria and discussed potential
      drug interactions that can enhance the magnesuric effect of digoxin. We suggest
      that during the administration of digoxin, clinicians should consider the
      presence of other causes of hypomagnesemia and hypermagnesuria that could enhance
      the magnesuric effect of digoxin, monitor the urinary and serum levels of
      magnesium and prescribe an oral supplementation of magnesium.

PMID- 29169162
TI  - Application of Electrocautery Needle Knife Combined with Balloon Dilatation
      versus Balloon Dilatation in the Treatment of Tracheal Fibrotic Scar Stenosis.
AB  - BACKGROUND: Electrocautery needle knives can largely reduce scar and granulation
      tissue hyperplasia and play an important role in treating patients with benign
      stricture. OBJECTIVE: The aim of this retrospective study was to evaluate the
      efficacy and safety of electrocautery needle knife combined with balloon
      dilatation versus balloon dilatation alone in the treatment of tracheal stenosis
      caused by tracheal intubation or tracheotomy. METHODS: We retrospectively
      analysed the clinical data of 43 patients with tracheal stenosis caused by
      tracheotomy or tracheal intubation in our department from January 2013 to January
      2016. Among these 43 patients, 23 had simple web-like stenosis and 20 had complex
      steno sis. All patients were treated under general anaesthesia, and the treatment
      methods were (1) balloon dilatation alone, (2) needle knife excision of fibrotic
      tissue combined with balloon dilatation, and (3) needle knife radial incision of
      fibrotic tissue combined with balloon dilatation. RESULTS: After treatment the
      symptoms, such as shortness of breath, were markedly improved immediately in all
      cases. The stenosis degree of patients who were treated with the elec-trocautery
      needle knife combined with balloon dilatation had better improvement compared
      with that of those treated with balloon dilatation treatment alone after 3 months
      (0.45 +/- 0.04 vs. 0.67 +/- 0.05, p < 0.01), and the proportion of restenosis
      occurrence that required further treatment was decreased at 6 months (46.9 vs.
      81.8%), especially for the web-like stenosis patients, as most of their stenoses
      dilated with no obvious restenosis and achieved clinical cure. CONCLUSION:
      Electrocautery needle knife combined with balloon dilatation is an effective and
      safe treatment for tracheal fibrotic stenosis compared with balloon dilatation
      alone.

PMID- 29169165
TI  - Giant Pseudoaneurysm of the Left Atrium after Pneumonectomy.

PMID- 29169164
TI  - A Novel PCM1-PDGFRB Fusion in a Patient with a Chronic Myeloproliferative
      Neoplasm and an ins(8;5).

PMID- 29169166
TI  - Acupuncture and Methylphenidate Drugs in Adults with Attention Deficit
      Hyperactivity Disorder: A Pilot Study of Self-Reported Symptoms.

PMID- 29169167
TI  - Structural Pulmonary Abnormalities Still Evident in Schoolchildren with New
      Bronchopulmonary Dysplasia.
AB  - BACKGROUND: A new pattern of bronchopulmonary dysplasia (BPD) has emerged with
      the improved survival of preterm children. OBJECTIVES: Our aim was to
      characterize structural abnormalities associated with new BPD and to evaluate
      whether the severity of high-resolution computed tomography (HRCT) changes is
      associated with lung function. METHODS: HRCT scans were performed on 21
      schoolchildren with a history of new BPD (mild, n = 9; moderate, n = 4; and
      severe, n = 8) with a mean age of 12.7 years (range: 8.7-16.7). Scans were
      interpreted by 2 radiologists using a structured scoring system. Spirometry
      (forced expiratory volume in 1 s [FEV1] and maximum mid-expiratory flow [MMEF])
      and the diffusion capacity of the lung for carbon monoxide (DLCO) were measured.
      RESULTS: At least 1 HRCT abnormality was evident in 17 children (81%), including
      linear-to-triangular subpleural opacities (71%), air trapping (29%), mosaic
      perfusion (24%), peribronchial thickening (14%), and emphysema (14%). The HRCT
      score was higher in the severe BPD group (11.50; 95% CI 2.86-20.14) than in the
      mild or moderate BPD group (1.39; 95% CI 0.24-2.54, and 2.75; 95% CI 0.28-5.22,
      respectively). HRCT scores were inversely related to FEV1 (beta -4.23; 95% CI 
      6.97 to -1.49, p = 0.004) and MMEF (beta -3.45; 95% CI -6.10 to -0.80, p = 0.013)
      but not to DLCO. The duration of the initial mechanical ventilation was
      associated with HRCT scores (p = 0.014). CONCLUSIONS: Structural lung
      abnormalities are common among schoolchildren with a history of new BPD,
      resembling abnormalities described in the presurfactant era. HRCT abnormalities
      are associated with the duration of early mechanical ventilation and the severity
      of BPD and they are correlated with spirometry.

PMID- 29169168
TI  - Anterior Borderzone Angle for Hemodynamic Collateral Metric in Patients with
      Symptomatic Middle Cerebral Artery Stenosis.
AB  - BACKGROUND AND AIMS: We aimed to introduce a parameter of anterior borderzone
      angle (ABZA) to quantitatively evaluate the ACA-MCA leptomeningeal collaterals
      for middle cerebral artery stenosis (MCAS). METHODS: Two hundred seventy-five
      patients with 50-100% MCAS and 100 controls were included. The 95% reference
      range of ABZA was obtained from the controls. ABZAtrans was defined as "ABZA/the
      95% upper limit." Relationships between ABZA and MCAS, -ABZAtrans and the TICI
      grade, the American Society of Interventional and Therapeutic
      Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grade
      were analyzed. An ABZA grade model for the ACA leptomeningeal collaterals was
      tentatively developed. RESULTS: The 95% reference range of ABZA was 0.0o-23.0o.
      ABZA was significantly associated with MCAS by a function of the fourth power (R2
      = 0.723, p < 0.001), and could predict hemodynamic MCAS (>=70%) with an AUC of
      0.928 (95% CI 0.903-0.953). ABZAtrans was negatively correlated with the TICI
      grade (rho = -0.752, p < 0.001) and positively with the ASITN/SIR grade (rho =
      0.921, p < 0.001). The ABZA grade was created by rounding -ABZAtrans to a nearest
      integer, and was closely associated with the ASITN/SIR grade (rho = 0.894, p <
      0.001). CONCLUSIONS: ABZA can be used as a hemodynamic parameter to
      quantitatively evaluate ACA leptomeningeal collaterals.

PMID- 29169169
TI  - Effects and Interactions of Prenatal Ethanol Exposure, a Post-Weaning High-Fat
      Diet and Gender on Adult Hypercholesterolemia Occurrence in Offspring Rats.
AB  - BACKGROUND/AIMS: Prenatal ethanol exposure (PEE) could induce intrauterine
      programming of hypothalamic-pituitary-adrenal axis-associated neuroendocrine
      metabolism, resulting in intrauterine growth retardation and susceptibility to
      adult hypercholesterolemia in offspring. This study aimed to analyse the effects
      and interactions of PEE, a post-weaning high-fat diet (HFD) and gender on the
      occurrence of adult hypercholesterolemia in offspring rats. METHODS: Wistar
      female rats were treated with ethanol (4 g/kg.d) at gestational days 11-20. The
      offspring were given a normal diet or HFD after weaning, and the blood
      cholesterol metabolism phenotype and expression of hepatic cholesterol metabolism
      related genes were detected in 24-week-old offspring. Furthermore, the
      interactions among PEE, HFD, and gender on hypercholesterolemia occurrence were
      analysed. RESULTS: PEE increased the serum total cholesterol (TCH) and low
      density lipoprotein-cholesterol (LDL-C) levels and decreased the serum high
      density lipoprotein-cholesterol (HDL-C) level in adult offspring rats; the
      changes in female offspring were greater than those in males. At the same time,
      the mRNA expression levels of hepatic cholesterol metabolic enzymes
      (apolipoprotein B (ApoB) and 7alpha-hydroxylase (CYP7A1))-were increased, while
      the mRNA expression levels of the scavenger receptor B1 (SR-B1) and LDL receptor
      (LDLR) were decreased. Furthermore, a three-way ANOVA showed there were
      interactions among PEE, post-weaning HFD and gender. For PEE offspring, a post
      weaning HFD aggravated the elevated hepatic ApoB and CYP7A1 expression and
      reduced SR-B1 and LDLR expression; the changes in hepatic SR-B1 and CYP7A1
      expression were greater in female HFD rats than in males. CONCLUSION: Our
      findings suggest that a post-weaning HFD could aggravate offspring
      hypercholesterolemia caused by PEE and that this mechanism might be associated
      with hepatic cholesterol metabolic disorders that are aggravated by a post
      weaning HFD; hepatic cholesterol metabolism was more sensitive to neuroendocrine
      metabolic alterations by PEE and a post-weaning HFD in the female offspring than
      in the male offspring.

PMID- 29169170
TI  - Mite-Induced Asthma and IgE Levels to Shrimp, Mite, Tropomyosin, Arginine Kinase,
      and Der p 10 Are the Most Relevant Risk Factors for Challenge-Proven Shrimp
      Allergy.
AB  - BACKGROUND: Shrimp sensitization is common in the general population, but the
      presence of symptoms is only moderately related to sensitization. A point still
      at issue is which in vivo and/or in vitro tests (food challenge, component
      resolved diagnosis, house dust mite [HDM] sensitization) can help in
      distinguishing shrimp-allergic subjects from subjects that are sensitized but
      tolerant. METHODS: The aim of this study was to evaluate the role of IgE to the
      different shrimp and mite allergens in distinguishing shrimp challenge-positive
      from challenge-negative patients. Subjects with suspected hypersensitivity
      reactions to shrimp, positive skin prick tests (SPTs), and/or anti-shrimp IgE
      were submitted to open and double-blind placebo-controlled food challenges
      (DBPCFC). Specific IgE to shrimp, mites, and the recombinants rPen a 1, rDer p 1,
      2, and 10 were tested using ImmunoCAP-FEIA. IgE immunoblotting was performed to
      identify the patients' allergenic profiles. RESULTS: In total, 13 out of 51
      (25.5%) patients with reported reactions to shrimp were truly shrimp allergic (7
      DBPCFC positive and 6 with documented severe reactions). These patients had
      significantly higher skin test wheal diameters than nonallergic patients, as well
      as higher levels of IgE to rPen a 1 and rDer p 10. HDM-induced asthma and the
      simultaneous presence of anti-nDer p 1, 2, and 10 IgE levels increased the risk
      of true shrimp allergy. CONCLUSION: Food challenge tests are mandatory for the
      diagnosis of shrimp allergy. Tropomyosin is associated with clinical reactivity.
      HDM-induced asthma and anti-mite IgE are risk factors for shrimp allergy.

PMID- 29169171
TI  - MiRNAs are Unlikely to be Involved in Retinoid Receptor Gene Regulation in
      Pancreatic Cancer Cells.
AB  - BACKGROUND/AIMS: Retinoid receptors and retinoic acid were reported to be down
      regulated in pancreatic duct adenocarcinoma (PDAC) compared to normal pancreas.
      Yet the mechanism of the down-regulation of retinoid receptors is not well
      defined. The aim of this study was to find out whether selected dysregulated
      miRNAs in PDAC are responsible for the decreased level of retinoid receptors.
      METHODS: Bioinformatics, real-time PCR, western blot analysis as well as
      molecular manipulation with miRNA in cells of PDAC were carried out. RESULTS: We
      first performed bioinformatics research to identify conserved target sequences
      for deregulated miRNAs within the 3'UTR region of retinoid receptor mRNA. This
      research revealed binding sites for miR-138, -27a, -27b, -206, -613, -9-5p, 
      27a/b-3p and -27a. Next, we investigated the expression of selected retinoid
      receptors and miRNAs in PDAC cell lines and in the Human Pancreatic Duct
      Epithelial (HPDE) cell line. Further, we investigated the effects of modifying
      expression levels of selected miRNAs using miRNA inhibitors or mimics. We
      demonstrated that none of these miRNAs can target the selected retinoid receptors
      in vitro. CONCLUSIONS: miR-27a, miR-27b, miR-9, miR10a and miR-10b were up
      regulated in PDAC cells compared to HPDE cells. The up-regulation of these miRNAs
      was not responsible for the down-regulation of RARalpha, RARbeta, RXRalpha and
      RXRbeta in PDAC cells.

PMID- 29169174
TI  - Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis
      Induction in Tumour Cells.
AB  - BACKGROUND/AIMS: Melatonin is a hormone transferring information about duration
      of darkness to the organism and is known to modulate several signaling pathways
      in the cells, e.g. generation of endoplasmic reticulum stress, oxidative status
      of the cells, etc. Melatonin has been shown to exert antiproliferative and
      cytotoxic effects on various human cancers. We proposed that this hormone can
      differently affect tumour cells and healthy cells. METHODS: We compared the
      effect of 24 h melatonin treatment on calcium transport (by fluorescent probes
      FLUO-3AM and Rhod-5N), ER stress (determined as changes in the expression of
      CHOP, XBP1 and fluorescently, using Thioflavin T), ROS formation (by CellROX(r)
      Green/Orange Reagent) and apoptosis induction (by Annexin-V
      FLUOS/propidiumiodide) in two tumour cell lines - ovarian cancer cell line A2780
      and stable cell line DLD1 derived from colorectal carcinoma, with non-tumour
      endothelial cell line EA.hy926. RESULTS: Melatonin increased apoptosis in both
      tumour cell lines more than twice, while in EA.hy926 cells the apoptosis was
      increased only by 30%. As determined by silencing with appropriate siRNAs, both,
      type 1 sodium/calcium exchanger and type 1 IP3 receptor are involved in the
      apoptosis induction. Antioxidant properties of melatonin were significantly
      increased in EA.hy926 cells, while in tumour cell lines this effect was much
      weaker. CONCLUSION: Taken together, melatonin has different antioxidative effects
      on tumour cells compared to non-tumour ones; it also differs in the ability to
      induce apoptosis through the type 1 sodium/calcium exchanger, and type 1 IP3
      receptor. Different targeting of calcium transport systems in tumour and normal,
      non-tumour cells is suggested as a key mechanism how melatonin can exert its
      anticancer effects. Therefore, it might have a potential as a novel therapeutic
      implication in cancer treatment.

PMID- 29169175
TI  - Bufalin Inhibits Cellular Proliferation and Cancer Stem Cell-Like Phenotypes via
      Upregulation of MiR-203 in Glioma.
AB  - BACKGROUND/AIMS: Prior studies have shown that bufalin inhibits cellular
      proliferation and induces apoptosis in various human cancers. MicroRNA-203 (miR
      203) has been shown to function as an important regulator of tumor progression at
      various stages. In this study, we investigated the effect of miR-203 expression
      and bufalin treatment on glioma cell proliferation and stem cell-like phenotypes.
      METHODS: We used cell viability assay, colony formation assay, cell apoptosis
      assay and neurosphere formation assay to dectect the treatment effect of bufalin
      on U251 and U87 cells. Cells were transfected with the miR-203 mimic without
      bufalin treatment or cells were transfected with anti-miR-203 under bufalin
      treatment, the above expreiments were repeated. RT-PCR was employed to quantify
      miR-203 expression. Western blot was performed to detect the stem cell-like (CSC)
      markers, OCT4 and SOX2. Luciferase activity assay was used to determine whether
      the SPARC is the target of miR-203. RESULTS: Bufalin treatment inhibited cell
      proliferation, colony formation, and CSC phenotypes and increased cell apoptosis
      and expression of miR-203. Furthermore, overexpression of miR-203 led to similar
      outcomes as bufalin treatment with respect to the cell viability, colony
      formation, cell apoptosis and the phenotypes of glioma cells. While anti-miR-203
      attenuated the inhibitory effects of bufalin as promoting cell proliferation,
      colony formation and CSC phenotyes and inhibiting cell apoptosis. In addition, we
      identified SPARC as a novel target gene of miR-203. CONCLUSIONS: These findings
      suggest that miR-203 plays an important role in bufalin's ability to inhibit the
      growth of glioma cells and the development of stem cell-like phenotypes.

PMID- 29169176
TI  - Ablation of ATG4B Suppressed Autophagy and Activated AMPK for Cell Cycle Arrest
      in Cancer Cells.
AB  - BACKGROUND/AIMS: ATG4B is a cysteine protease required for autophagy, which is a
      cellular catabolic pathway involved in energy balance. ATG4B expression is
      elevated during tumor growth in certain types of cancer, suggesting that ATG4B is
      an attractive target for cancer therapy. However, little is known about the
      mechanisms through which ATG4B deprivation suppresses the growth of cancer cells.
      METHODS: Cancer cells were transfected with either siRNA against ATG4B or an
      expression vector encoding wild-type ATG4BWT or encoding catalytic mutant
      ATG4BC74A to determine cell cycle progression by propidium iodide staining or by
      BrdU incorporation assay using flow cytometry. The GFP-MAP1LC3-II puncta and
      protein levels in the cells were determined by immunofluorescence and
      immunoblotting, respectively. RESULTS: Knockdown of ATG4B blocked cell
      proliferation, particularly at the G1-S phase transition, in various cancer
      cells. Moreover, knockdown of ATG4B or overexpression of the ATG4BC74A catalytic
      mutant reduced both autophagic flux and ATP levels and increased AMP-activated
      protein kinase (AMPK) phosphorylation in the cancer cells. Nevertheless,
      knockdown of ATG4B had only a minor effect on AMPK activation and G1 phase arrest
      in liver kinase B1 (LKB1)-deficient or AMPK-inhibited cancer cells. CONCLUSION:
      These results imply that targeting ATG4B might inhibit autophagy and trigger the
      LKB1-AMPK energy-sensing pathway, resulting in tumor growth suppression.

PMID- 29169177
TI  - Acute Kidney Injury in Elderly Population: A Prospective Observational Study.
AB  - BACKGROUND/AIMS: Acute kidney injury (AKI) has been reported as a recognized
      condition among the elderly population; however, its clinical epidemiology is
      still poorly evaluated. We propose to evaluate the epidemiological profile of AKI
      in hospitalized elderly patients and the variables associated with renal
      replacement therapy (RRT) dependency at discharge after an episode of AKI.
      METHODS: This prospective observational study enrolled 286 elderly patients (aged
      >=60 years), who had a diagnosis of AKI and were admitted to a tertiary care
      hospital. Clinical data were analyzed, which included RRT indication, referral
      time to nephrologist support, standby period in the emergency care units (ECU)
      before a transfer to an intensive care unit, staff criteria used to indicate
      palliative care, and the incidence of patients who stayed on chronic dialysis for
      at least 6 months after discharge. RESULTS: The overall hospital mortality was
      56.3%. Acute Kidney Injury Network (AKIN) 3 at the time of admission was
      significantly higher in patients who underwent RRT. Intrinsic AKI (p < 0.001),
      AKIN 3 (p < 0.001), RRT (p < 0.001), and increased length of stay in ECUs (p =
      0.01) all had a significantly higher prevalence among non-survivors. On
      multivariate analysis, however, only renal aetiology (intrinsic AKI) was
      independently associated with mortality (OR 2.88; 95% CI [1.29-6.13]).
      Approximately 85% of the discharged patients (n = 125) were dialysis free and
      36.4% of them who had a previous diagnosis of chronic kidney disease (CKD) upon
      admission had a worse renal function. Age, AKIN 3, RRT, prior history of CKD,
      diabetes mellitus, and the number of hemodialysis sessions showed to have an
      impact on dialysis dependence. Furthermore, 24 of 161 patients who had a dialysis
      indication were placed on palliative care. CONCLUSIONS: The severity of AKI and
      the need for RRT were risk factors for mortality and dependence on dialysis.
      Antecedents of CKD seem to be associated with a poor renal outcome following an
      AKI episode. Starting RRT had an impact on the clinical decision to enroll these
      patients into palliative care.

PMID- 29169178
TI  - Subjective Assessment of Sleep in Huntington Disease: Reliability of Sleep
      Questionnaires Compared to Polysomnography.
AB  - INTRODUCTION: The aim of the study was to evaluate the clinical reliability of
      subjective sleep evaluation, based on sleep and psychometric questionnaires, by
      comparing the results with those obtained with laboratory-based video
      polysomnography (V-PSG). PATIENTS AND METHODS: Thirty consecutive Huntington
      disease (HD) patients were enrolled. Subjective evaluation of sleep included the
      Pittsburgh Sleep Quality Index (PSQI), the sleep questionnaire for HD (HDQ), the
      Epworth Sleepiness Scale, the Bologna questionnaire for sleepiness (BQ), the
      Berlin questionnaire, and the RBD questionnaire; the International Restless Legs
      Syndrome Study Group scale was administered to patients with positive screening.
      The psychometric evaluation included the Zung Anxiety Scale, the short form of
      the Beck Depression Inventory, and the Maudsley Obsessive-Compulsive Inventory.
      All patients underwent V-PSG. RESULTS: In sleepiness evaluation, the Epworth
      score was above the cutoff in 6 subjects, and the BQ detected a "high risk" of
      sleepiness in 7 cases. The results were concordant in 24 and discordant in 5
      cases. In the evaluation of sleep quality, the PSQI score was above the cutoff in
      18 subjects. According to the HDQ, 10 subjects were poor sleepers. The results
      were concordant with the PSQI in 20 subjects. DISCUSSION: All comparisons between
      scale scores and PSG results showed poor or totally absent concordance between
      subjective and objective measures. SIGNIFICANCE: The subjective evaluation of
      sleep in HD patients shows a poor correlation with PSG results.

PMID- 29169179
TI  - Apolipoprotein E e4 Allele Is Associated with Subjective Cognitive Decline: A
      Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) is a condition
      associated with increased risk of Alzheimer's disease. This study performs a meta
      analysis to estimate the prevalence of the Apolipoprotein E e4 (APOE e4) allele
      in SCD and the association of APOE e4 with SCD. METHODS: The MEDLINE, EMBASE, and
      Cochrane Library databases were searched. Meta-analyses were conducted using
      STATA 12.0 software. When significant heterogeneity was present (I2 >50% and p <
      0.05), we conducted stratified and meta-regression analyses to explore possible
      reasons for heterogeneity. RESULTS: We selected a total of 28 studies that were
      conducted in Australia, the United States, northern Europe, middle Europe,
      southern Europe, and Asia. The sample size of the SCD group was 6,044. Thirteen
      studies included a healthy control group (total control cohort of 3,822), whereas
      the remaining 15 studies were single-arm studies of SCD groups. The APOE e4
      allele was associated with SCD (OR 1.12 [1.00-1.25]; p = 0.04). The pooled
      estimate for APOE e4 carrier prevalence was 32% (95% CI 28-35). Due to the
      significant heterogeneity in prevalence estimates, we performed stratified and
      meta-regression analyses and found that age and northern European residency were
      significantly associated with heterogeneity. CONCLUSION: The results of this meta
      analysis indicate a weak association between APOE e4 and SCD. Age and northern
      European residency are the critical factors that determine heterogeneity in the
      APOE e4-associated prevalence of SCD.

PMID- 29169180
TI  - Mitochondria-Targeted Antioxidant Mito-Tempo Protects Against Aldosterone-Induced
      Renal Injury In Vivo.
AB  - BACKGROUND/AIMS: Growing evidence suggests mitochondrial dysfunction (MtD) and
      the Nlrp3 inflammasome play critical roles in chronic kidney disease (CKD)
      progression. We previously reported that Aldosterone (Aldo)-induced renal injury
      in vitro is directly caused by mitochondrial reactive oxygen species (mtROS)
      mediated activation of the Nlrp3 inflammasome. Here we aimed to determine whether
      a mitochondria-targeted antioxidant (Mito-Tempo) could prevent Aldo-induced
      kidney damage in vivo. METHODS: C57BL/6J mice were treated with Aldo and/or Mito
      Tempo (or ethanol as a control) for 4 weeks. Renal injury was evaluated by
      Periodic Acid-Schiff reagent or Masson's trichrome staining and electron
      microscopy. ROS were measured by DCFDA fluorescence and ELISA. MtD was determined
      by real-time PCR and electron microscopy. Activation of the Nlrp3 inflammasome
      and endoplasmic reticulum stress (ERS) was detected via western blot. RESULTS:
      Compared with control mice, Aldo-infused mice showed impaired renal function,
      increased mtROS production and MtD, Nlrp3 inflammasome activation, and elevated
      ERS. We showed administration of Mito-Tempo significantly improved renal function
      and MtD, and reduced Nlrp3 inflammasome activation and ERS in vivo. CONCLUSION:
      Mitochondria-targeted antioxidants may attenuate Aldo-infused renal injury by
      inhibiting MtD, the Nlrp3 inflammasome, and ERS in vivo. Therefore, targeting
      mtROS might be an effective strategy for preventing CKD.

PMID- 29169182
TI  - Gemcitabine plus platinum-based chemotherapy for first-line treatment of
      hepatocholangiocarcinoma: an AGEO French multicentre retrospective study.
AB  - BACKGROUND: Hepatocholangiocarcinoma (cHCC-ICC) is a rare liver tumour for which
      no data on chemosensitivity exist. The aims of this multicentre study were to
      evaluate overall survival (OS), progression-free survival (PFS), and prognostic
      factors in cHCC-ICC treated by gemcitabine plus platinum as first-line. METHODS:
      Unresectable cHCC-ICC treated by gemcitabine plus platinum-based chemotherapy
      between 2008 and 2017 were retrospectively analysed. Diagnosis was based on
      histology or, in case of ICC or HCC histology, on discordant computerised
      tomography scan enhancement patterns associated with discordant serum tumour
      marker elevation suggesting the alternative tumour. OS and PFS were evaluated by
      Kaplan-Meier method and prognostic factors by Log-rank test and Cox model.
      RESULTS: Among 30 patients included, cHCC-ICC was histologically proven in 22
      (73.3%). 18 (60%) received gemcitabine plus oxaliplatin (GEMOX), 9 (30%) GEMOX
      plus bevacizumab, and 3 (10%) gemcitabine plus cisplatin. RECIST criteria were
      reported in 28 patients: 8 (28.6%) showed partial response, 14 (50%) stable
      disease, and 6 (21.4%) tumour progression at first evaluation. Median PFS and OS
      were 9.0 and 16.2 months, respectively. Serum bilirubin ?30 MUmol l-1 (P=0.001)
      and positive serology for HBV and/or HCV (P=0.014) were independent poor
      prognostic factors for OS. CONCLUSIONS: Gemcitabine plus platinum-based
      chemotherapy is effective as first-line for advanced cHCC-ICC.

PMID- 29169181
TI  - Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced
      dormancy.
AB  - BACKGROUND: Breast cancers can recur after a long latency period following
      'successful' primary treatments. Chronic inflammation significantly correlates
      with reduced diseased-free survival in breast cancer patients and could be a
      point of intervention to prevent recurrence. Liver is among the main sites of
      breast cancer recurrence. Thus, we hypothesise that inflammatory signals from
      hepatic stellate cells, the major inflammatory regulators in the sinusoid, could
      stimulate dormant cancer cells to emerge. METHODS: We utilise in vitro co-culture
      of breast cancer cells with stellate cells and an ex vivo 3D human liver micro
      physiologic system to identify stellate cells-derived factors that mediate tumour
      emergence. RESULTS: Activated, but not quiescent, hepatic stellate cells secreted
      soluble factors to induce the proliferation of MCF7 and MDA-MB231 cancer cells.
      IL-8 and MCP-1 were highly secreted by the activated stellate cells and primary
      human non-parenchymal cells. IL-8 significantly reduced serum-starvation growth
      arrest on MDA-MB231 cells in vitro and increased cancer proliferation ex vivo.
      Blocking IL-8Rb/CXCR2 reduced IL-8-induced cancer growth and proliferation.
      CONCLUSIONS: Activated stellate cells can induce breast cancer emergence from
      dormancy in the liver by secreting inflammatory cytokines. Preventing liver
      inflammation or disrupting the subsequent key cytokines may prevent metastatic
      outgrowth.

PMID- 29169183
TI  - MYC regulation of glutamine-proline regulatory axis is key in luminal B breast
      cancer.
AB  - BACKGROUND: Altered cellular metabolism is a hallmark of cancer and some are
      reliant on glutamine for sustained proliferation and survival. We hypothesise
      that the glutamine-proline regulatory axis has a key role in breast cancer (BC)
      in the highly proliferative classes. METHODS: Glutaminase (GLS), pyrroline-5
      carboxylate synthetase (ALDH18A1), and pyrroline-5-carboxylate reductase 1
      (PYCR1) were assessed at DNA/mRNA/protein levels in large, well-characterised
      cohorts. RESULTS: Gain of PYCR1 copy number and high PYCR1 mRNA was associated
      with Luminal B tumours. High ALDH18A1 and high GLS protein expression was
      observed in the oestrogen receptor (ER)+/human epidermal growth factor receptor
      (HER2)- high proliferation class (Luminal B) compared with ER+/HER2- low
      proliferation class (Luminal A) (P=0.030 and P=0.022 respectively), however this
      was not observed with mRNA. Cluster analysis of the glutamine-proline regulatory
      axis genes revealed significant associations with molecular subtypes of BC and
      patient outcome independent of standard clinicopathological parameters (P=0.012).
      High protein expression of the glutamine-proline enzymes were all associated with
      high MYC protein in Luminal B tumours only (P<0.001). CONCLUSIONS: We provide
      comprehensive clinical data indicating that the glutamine-proline regulatory axis
      plays an important role in the aggressive subclass of luminal BC and is therefore
      a potential therapeutic target.

PMID- 29169185
TI  - Co-culture of human alveolar epithelial (hAELVi) and macrophage (THP-1) cell
      lines.
AB  - The air-blood barrier is mainly composed of alveolar epithelial cells and
      macrophages. Whereas the epithelium acts as a diffusional barrier, macrophages
      represent an immunological barrier, in particular for larger molecules and
      nanoparticles. This paper describes a new co-culture of human cell lines
      representing both cell types. Acquiring, culturing and maintaining primary
      alveolar epithelial cells presents significant logistical and technical
      difficulties. The recently established human alveolar epithelial lentivirus
      immortalized cell line, hAELVi, when grown on permeable filters, form monolayers
      with high functional and morphological resemblance to alveolar type I cells. To
      model alveolar macrophages, the human cell line THP-1 was seeded on pre-formed
      hAELVi monolayers. The co-culture was characterized regarding cellular
      morphology, viability and barrier function. Macrophages were homogenously
      distributed on the epithelium and could be kept in co-culture for up to 7 days.
      Transmission electron microscopy showed loose contact between THP-1 and hAELVi
      cells. When grown at air liquid interface, both cells were covered with
      extracellular matrix-like structure, which was absent in THP-1 mono culture. In
      co-culture with macrophages, hAELVi cells displayed similar, sometimes even
      higher, trans-epithelial electrical resistance than in mono-cultures. When
      exposed to silver and starch NPs, hAELVi mono-cultures were more tolerant to the
      particles than THP-1 mono-cultures. The viability in the co-culture was similar
      to that of hAELVi monocultures. Transport studies with sodium fluorescein in
      presence/absence of EDTA proved that the co culture acts as functional diffusion
      barrier. These data demonstrate that hAELVi-/THP-1 co-cultures represent a
      promising model for safety and permeability studies of inhaled chemicals, drugs
      and nanoparticles.

PMID- 29169186
TI  - Prenylated Flavonoids and Phenolic Compounds from the Rhizomes of Marine
      Phanerogam Cymodocea nodosa.
AB  - Chemical investigation of the rhizomes of the marine phanerogam Cymodocea nodosa
      resulted in the isolation of two new prenylated flavon-di-O-glycosides,
      cymodioside A (1: ) and B (2: ), along with known phenolic compounds 3: -7: ,
      some of which never reported from seagrasses to date. The structures of compounds
      1: and 2: were established by extensive nuclear magnetic resonance analysis. In
      addition, the absolute configuration of 4-(2,5-dihydroxyhexyl) benzene-1,2-diol
      (7: ), which was not previously reported in the literature, has been now
      determined.

PMID- 29169184
TI  - HER2 expression patterns in paired primary and metastatic endometrial cancer
      lesions.
AB  - BACKGROUND: Despite successful implementation of drugs targeting the human
      epidermal growth factor receptor 2 (HER2) receptor in breast and gastric cancers,
      the potential of HER2 as a therapeutic target in other cancers has been less
      studied, including endometrial cancer. We investigated expression levels of HER2
      (ERBB2) in a large cohort of endometrial cancer lesions, also including complex
      atypical hyperplasia and metastatic lesions. METHODS: 67 precursor lesions, 790
      primary endometrial cancers and 383 metastatic lesions were investigated for HER2
      expression in relation to clinicopathologic features and outcome. Protein levels
      were assessed by immunohistochemistry (using the HercepTest and staining index
      (SI) criteria), mRNA levels by microarrays and amplification status by
      chromogenic in situ hybridisation. RESULTS: High HER2 protein levels were
      significantly associated with features of aggressive disease and increased mRNA
      ERBB2 levels. HER2 expression defined by the SI proved to be a better predictor
      of survival compared with the HercepTest. A discordant HER2 expression pattern
      between paired primary and metastatic lesions was detected, revealing substantial
      reduction in HER2 expression from primary to metastatic disease. CONCLUSIONS:
      Loss of HER2 expression is common in metastatic endometrial cancer lesions and
      assessment of HER2 levels in the metastatic lesions may be important to define
      the potential benefit of anti-HER2 treatments in endometrial cancer patients.

PMID- 29169187
TI  - Biologically Active Orbitides from the Euphorbiaceae Family.
AB  - A comprehensive overview of natural orbitides isolated from Euphorbiaceae species
      and their most relevant biological activities are presented. Euphorbiaceae is a
      large and diverse family, which comprises about 300 genera, and is known as an
      important source of medicines and toxins. Several classes of secondary
      metabolites have been described for this taxon, however, orbitides have been
      broadly reported in Jatropha and Croton genera. Additionally, the latex is
      documented as the main source of orbitides in this family. Based on their
      structural and functional diversity, orbitides present a large variety of
      biological activities described as cytotoxicity, antimalarial, antibacterial,
      antifungal, enzymatic inhibition, and immunosuppressive, although the mechanism
      of action still needs to be further investigated. In recent years, the discovery
      of bioactive cyclic peptides from different sources has grown exponentially,
      making them promising molecules in the search for new drug leads. This review
      also highlights the attempts made by many researchers to organize the orbitides
      nomenclature and amino acid numbering, as well the important progress recently
      achieved in the biosynthetic study area.

PMID- 29169188
TI  - Cardiac Autonomic Function, Cardiovascular Risk and Physical Activity in
      Adolescents.
AB  - The aims of this study were to investigate in adolescents: 1) the relationships
      of physical activity (PA) and cardiorespiratory fitness (CRF) to traditional CVD
      risk factors, rest and recovery autonomic function; and 2) whether autonomic
      function strengthens the associations between PA, CRF and CVD risk. Fifty-four
      (22 girls) adolescents had traditional CVD risk factors, rest and recovery
      autonomic function evaluated. CRF was measured using a steep ramp cycle test and
      PA was assessed with accelerometers. Resting HRV (and RMSSD30) and heart rate
      recovery (T30, HHRtau) were used. Clustered traditional (CVDRtrad) and autonomic
      (CVDRauto) risk scores were created and added to form a composite clustered CVD
      risk score (CVDRcom). PA and CRF were significantly and negatively associated
      with traditional CVD risk factors. Moderate (MPA) and vigorous (VPA) were
      positively related to resting RMSSD, and negatively related to T30 and HHRtau
      (all P<0.05). RMSSD30 recovered faster in the high compared to low median split
      for VPA. Stronger associations for CVDRcom compared to CVDRtrad were observed for
      MPA (CVDRcom: r2=0.32, P=<0.001; CVDRtrad: r2=0.17, P=0.002), and VPA (CVDRcom:
      r2=0.18, P=0.001; CVDRtrad: r2=0.06, P=0.08). These findings strengthen the
      proposed additional beneficial effects of PA on autonomic function above
      traditional CVD risk factors.

PMID- 29169189
TI  - Lifelong Voluntary Exercise Modulates Age-Related Changes in Oxidative Stress.
AB  - The hypothesis that aging and regular physical activity could influence oxidative
      stress has been studied by comparing antioxidant activities (superoxide dismutase
      (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), ascorbic acid
      and alpha-Tocopherol) and malondialdehyde level (MDA) in four groups: young
      sedentary (n=15; age: 20.3+/-2.8 years; YS), young active (n=16; age: 21.4+/-1.9
      years; YA), old sedentary (n=15; age: 65.1+/-3.5 years; OS) and old active (n=17;
      age: 67.2+/-4.8 years; OA). Antioxidant activities and MDA level were assessed at
      rest and after an incremental exercise. There was no difference in resting
      antioxidant activities and lipid peroxidation between YS and OS. However, resting
      SOD and GR activities were higher in YA compared to OA (p<0.01 and p<0.05,
      respectively) and resting MDA level was higher in OA compared to YA (p<0.01).
      After exercise, a significant increase in SOD and GPX activities was observed in
      YS, YA and OA (p<0.01). Likewise, after exercise a significant increase of MDA
      level in YA, OS and OA (p<0.01) was observed. In addition, the comparison of YA
      to OA and YS to OA revealed similar antioxidant activities and lipid peroxidation
      between YS and OA, whereas antioxidant activities were higher in YA compared to
      OA. These data suggest that beneficial effects of regular physical activity in
      antioxidant defense and lipid peroxidation damage could be impaired by the aging
      process and that regular physical activity in older adults could maintain age
      related decreases in antioxidant defense.

PMID- 29169190
TI  - Measurement of Basal Serum Calcitonin for the Diagnosis of Medullary Thyroid
      Cancer.
AB  - Calcitonin (CT), a tumor marker for medullary thyroid cancer (MTC), can be
      stimulated with pentagastrin or calcium. Because of the unavailability of
      pentagastrin, basal CT measurement is frequently used for the preoperative
      diagnosis of MTC. The aim of the study was to define basal serum calcitonin (bCT)
      cut-off thresholds for diagnosing MTC. Within a retrospective analysis, 114
      patients (51 males) were included fulfilling the criteria of an increased
      preoperative bCT level (>10 pg/ml) and the criteria of an available postoperative
      histology analysis. Based on a ROC plot analysis, the cut-off values for the
      diagnosis of MTC vs. non-malignancy (C cell hyperplasia and goiter) were
      identified. The most precise bCT thresholds for the identification of MTC were
      >=46 pg/ml for males (sensitivity: 93.6%, specificity: 95.0%, PPV: 97%, NPV: 90%)
      and >=35 pg/ml for females (sensitivity: 87.3%, specificity: 87.5%, PPV: 98%,
      NPV: 50%). Using these cut-offs, only 6% of male patients were not identified of
      having MTC, whereas 5% were false positive (having instead C cell hyperplasia).
      In females, the discrepancy was higher since 13% of female MTC patients were
      false negative by using the cut-off of >=35 pg/ml, and 13% had false positive
      results (suffering from C cell hyperplasia). Gender-specific bCT cut-offs for the
      identification of MTC vs. C cell hyperplasia and non-malignancy were defined,
      which can be used in clinical routine. In female patients, however, the accuracy
      is much lower compared to males.

PMID- 29169191
TI  - The Latest Developments of Functional Molecular Imaging in the Diagnosis of
      Primary Aldosteronism.
AB  - Differentiation of unilateral from bilateral aldosterone hypersecretion is the
      essential step in the clinical practice of primary aldosteronism (PA). Although
      adrenal venous sampling (AVS) has been established as the most standard test
      recommended by the guideline, its invasive and technically difficult nature has
      facilitated the approach to develop non-invasive functioning imaging as an
      alternative test. Compared to the conventional adrenocortical scintigraphy with
      cholesterol derivatives as tracer, the first-generation imaging, both of 11C
      MTO/PET and 123I-IMTO/SPECT/CT, the second-generation imaging, bind with high
      specificity and affinity to CYP11B enzymes and have advantages in shortening the
      time for obtaining specific images, reducing the radiation exposure to the
      patient, and resolution of the images. Because of very short half-life of 11C
      MTO, 123I-IMTO has a potential for a wider application than 11C-MTO. Sensitivity
      of identifying an adenoma smaller than 1 cm in diameter is still a common
      limitation of these new functional imaging methods. The new functional imaging
      could be supplementary to AVS in lateralization of PA when the results of AVS are
      not conclusive. To be a substitute for AVS, however, it should fulfill various
      conditions including high selectivity and binding affinity to CYP11B2, high
      sensitivity in detecting small adenoma, high resolution image, reduction of
      radiation exposure, and general versatility. Considering the potential number of
      patients, cost-effectiveness of the subtype testing in the clinical practice of
      PA could be one of the issues of the medical expenses. Thus, development of a new
      non-invasive functional imaging will have a significant impact on the clinical
      practice of PA and hypertension.

PMID- 29169192
TI  - A novel triple-anchoring technique for hybrid endoscopic mucosal resection.

PMID- 29169193
TI  - Application of over-the-scope clip for massive duodenal ulcer bleeding in a 4
      year-old boy weighing 7.8 kg.

PMID- 29169194
TI  - Intraductal radiofrequency ablation of an intraductal papillary mucinous
      neoplasia of the main pancreatic duct.

PMID- 29169195
TI  - Wide-field piecemeal cold snare polypectomy of large sessile serrated polyps
      without a submucosal injection is safe.
AB  - : BACKGROUND AND STUDY AIMS : Large series suggest endoscopic mucosal resection
      is safe and effective for the removal of large (>= 10 mm) sessile serrated polyps
      (SSPs), but it exposes the patient to the risks of electrocautery, including
      delayed bleeding. We examined the feasibility and safety of piecemeal cold snare
      polypectomy (pCSP) for the resection of large SSPs. METHODS: Sequential large
      SSPs (10 - 35 mm) without endoscopic evidence of dysplasia referred over 12
      months to a tertiary endoscopy center were considered for pCSP. A thin-wire snare
      was used in all cases. Submucosal injection was not performed. High definition
      imaging of the defect margin was used to ensure the absence of residual serrated
      tissue. Adverse events were assessed at 2 weeks and surveillance was planned for
      between 6 and 12 months. RESULTS: 41 SSPs were completely removed by pCSP in 34
      patients. The median SSP size was 15 mm (interquartile range [IQR] 14.5 - 20 mm;
      range 10 - 35 mm). The median procedure duration was 4.5 minutes (IQR 1.4 - 6.3
      minutes). There was no evidence of perforation or significant intraprocedural
      bleeding. At 2-week follow-up, there were no significant adverse events,
      including delayed bleeding and post polypectomy syndrome. First follow-up has
      been undertaken for 15 /41 lesions at a median of 6 months with no evidence of
      recurrence. CONCLUSIONS: There is potential for pCSP to become the standard of
      care for non-dysplastic large SSPs. This could reduce the burden of removing SSPs
      on patients and healthcare systems, particularly by avoidance of delayed
      bleeding.

PMID- 29169196
TI  - Peroral endoscopic myotomy in treatment-naive achalasia patients versus prior
      treatment failure cases.
AB  - BACKGROUND AND STUDY AIM: Peroral endoscopic myotomy (POEM) has emerged as an
      effective treatment modality for achalasia. Prior treatment may affect the
      outcomes of subsequent management. In this study, we aimed to compare the safety
      and efficacy of POEM in treatment-naive patients vs. those with prior treatment
      failure (PTF). PATIENTS AND METHODS: The data of consecutive patients with
      achalasia who underwent POEM at a single tertiary care center from January 2013
      to November 2016 were analyzed retrospectively. A comparative analysis was
      performed between treatment-naive and PTF cases. Technical and clinical success,
      adverse events, and operative time for POEM were compared between the two groups.
      RESULTS: Overall, 502 patients with achalasia underwent POEM during the study
      period: 260 patients (51.8 %) in the treatment-naive group and 242 patients (48.2
      %) in the PTF group. The mean operative time was significantly longer in the PTF
      group compared with the treatment-naive group (74.9 +/- 30.6 vs. 67.0 +/- 27.1
      minutes; P  = 0.002). On multivariate analysis, type of achalasia, dilated
      esophagus ( > 6 cm), disease duration, prior treatment, occurrence of adverse
      events, and type of knife used were significant predictors of operative time.
      Technical success (98.1 % vs. 97.1 %; P = 0.56) and clinical success (92.4 % vs.
      92.5 %; P  = 0.95) were comparable in the treatment-naive and PTF cases,
      respectively. Occurrence of gas-related events and mucosotomy were similar in
      both groups. Elevated DeMeester score was found in 17 /53 patients (32.1 %) in
      the PTF group and in 11 /44 patients (25.0 %) in the treatment-naive group (P =
      0.50). CONCLUSION: POEM is safe and equally effective for treatment-naive
      patients and for those in whom prior treatment has failed. POEM should be
      considered the treatment of choice in patients in whom prior treatment has
      failed.

PMID- 29169197
TI  - Sex-Dependent Effect of Metformin on Serum Prolactin Levels In Hyperprolactinemic
      Patients With Type 2 Diabetes: A Pilot Study.
AB  - BACKGROUND: Metformin was found to reduce circulating levels of pituitary
      hormones. OBJECTIVE: The purpose of this study was to assess whether sex
      determines the effect of metformin on lactotroph secretory function. METHODS: The
      study population included 25 women and 12 men with mildly elevated serum
      prolactin levels (25-75 ng/mL). Because of concomitant type 2 diabetes, all
      participants were treated with metformin (3 g daily). Plasma levels of glucose
      and lipids, HOMA1-IR, serum levels of prolactin, thyrotropin and free thyroid
      hormones, as well as Jostel's, SPINA-GT and SPINA-GD indices were assessed at
      baseline and at the end of metformin treatment. RESULTS: The study completed 24
      women and 11 men. At baseline, there were no significant differences in
      circulating levels of glucose and lipids, insulin sensitivity, hormones,
      Jostel's, SPINA-GT and SPINA-GD indices between women and men. In both men and
      women, metformin reduced fasting glucose levels and HOMA1-IR. However, only in
      women metformin decreased elevated prolactin levels and this effect correlated
      with an improvement insulin sensitivity, as well as with the impact on SPINA-GT.
      CONCLUSIONS: The results of the study suggest that the effect of metformin on
      serum prolactin levels is sex-dependent.

PMID- 29169198
TI  - [Changes in Sense of Coherence, Mental Distress and Satisfaction with Life and
      Studies in the Course of Psychosocial Counselling].
AB  - "Sense of coherence" (SOC) plays an essential role in the maintenance or recovery
      of health, according to the salutogenetic approach of Aaron Antonovsky. Empirical
      studies provide evidence of significant links between sense of coherence and
      different indicators of mental health. In the present study, the effectivity of
      an integrative counselling concept for the promotion of sense of coherence,
      reduction of mental distress and improvement of satisfaction with life was tested
      in a sample of 153 clients and patients. Correlations of SOC with mental distress
      and satisfaction with life and studies indicate a strong association. After
      psychosocial counselling according to the integrative ABCDE-model, significant
      pre-/post- changes with moderate to high effect sizes could be achieved. These
      findings bring important implications for the modifiability of the sense of
      coherence and provide evidence that the integrative ABCDE-model of psychosocial
      counseling might be effective. Correlations between ratings of the dimensions of
      the model and pre-/post changes are discussed.

PMID- 29169199
TI  - [Internet Addiction, Suicidality and Non-Suicidal Self-Harming Behavior - A
      Systematic Review].
AB  - BACKGROUND: Internet addiction (IA) is associated with a high rate of co-morbid
      mental disorders, especially depression, anxiety disorders, ADHD and personality
      disorders and a considerable level of psychological strain. In terms of risk
      assessment, the present work investigates the current research literature on
      suicidal behavior and non-suicidal self-injurious behavior (NSSI). METHODS: We
      performed a systematic literature search in 14 databases on title and abstract
      level for the most common keywords for IA, NSSI and suicidality. After deduction
      of multiple items, 2334 articles remained. They were filtered per inclusion and
      exclusion criteria. We identified studies that examined the relationship between
      IA, NSSI and suicidality, which were assessed by validated psychometric
      instruments. This allowed a total of 15 studies to be included. RESULTS: The
      relationship between IA and suicidality was examined in 10 studies, four studies
      examined the relationship of IA, suicidality, and NSSI, and one study exclusively
      focused on IA and NSSHB. All studies showed higher prevalence for NSSI and
      respectively suicidality of the subjects with an IA compared to subjects without
      IA, with point prevalence varying considerably between 1.6-18.7%. DISCUSSION: The
      results of the included publications suggest that Internet dependency is
      associated with an increased rate of non-suicidal self-harming behavior and
      increased suicidality, with suicidal ideation being more closely related to IA
      than suicidal actions. In order to develop a better understanding of causal
      relationships between IA, NSSI and suicidality, further longitudinal studies are
      required. CONCLUSION:  Against the background of the presented studies NSSHB and
      suicidality need to be explicitly addressed within the assessment and treatment
      of IA patients.

PMID- 29169200
TI  - [German Language Version and Validation of the Risk-Taking Behaviour Scale (RBS
      K) for High-Risk Sports].
AB  - Background High-risk sports, particularly climbing, kayaking and extreme skiing,
      have become increasingly popular. The most widely used psychological survey
      instrument with regard to risk behaviour in sports is the Sensation Seeking
      Model, mostly assessed by the Sensation Seeking Scale (SSS-V). Until recently,
      the literature discussed risk behaviour solely through this model. However, this
      scale does not measure risk-taking behaviours. In contrast, the Risk-Taking
      Behaviour Scale (RBS-K) is a three-item scale that measures risk behaviour in
      high-risk sports. This study aimed to validate a German language version of the
      RBS-K. Methods The RBS-K was translated and back-translated between English and
      German. High-risk sports participants (n = 2399) completed the German version of
      the RBS-K. Of those participants, 820 completed the RBS-K in person as part of a
      field survey and 1579 participated in an online survey. To validate the
      questionnaire, the SSS-V, accident involvement, age and sex were evaluated. The
      RBS-K divides the sample into deliberate risk takers (mean + standard deviation)
      and risk-averse persons (mean - standard deviation). We tested for internal
      consistency and correlations with SSS-V, age, sex and accident involvement. Group
      differences were calculated between deliberate risk takers and risk-averse
      persons. Results For internal consistency, we obtained a Cronbach's alpha of 0.56
      and a McDonald's omega of 0.63. Significant correlations were shown between RBS-K
      and SSS-V as well as age and sex. Compared to risk-averse persons (n = 643, 26.8
      %), deliberate risk takers (n = 319, 13.3 %) scored significantly higher in
      sensation seeking, were significantly younger and primarily male and had a
      significantly higher accident involvement. Conclusion The RBS-K discriminates
      well for age, sex and accident involvement. Also, correlations between the RBS-K
      and the well-established SSS-V are acceptable. With regard to the results and its
      compact design, the scale seems to be well suited for field surveys. We discuss
      the relatively modest internal consistency in the context of the small number of
      items and the different dimensions of risk-taking.

PMID- 29169201
TI  - Emergency off-pump CABG in a patient with Takotsubo cardiomyopathy and coronary
      artery disease.

PMID- 29169202
TI  - Accessory mitral valve mimicking aortic valve endocarditis as a cause of
      cerebrovascular accident.
AB  - Accessory mitral valve (AMV) is a rare congenital cardiac malformation associated
      with left ventricular outflow tract obstruction and endocarditis. We report a
      patient with an AMV who presented with a cerebellar infarct and discuss the
      management of this anomaly.

PMID- 29169203
TI  - Dissipation, residues and risk assessment of spirotetramat and its four
      metabolites in citrus and soil under field conditions by LC-MS/MS.
AB  - A modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method for
      the simultaneous determination of spirotetramat and its four metabolite residues
      in citrus, peel, pulp and soil was developed and validated by liquid
      chromatography with tandem mass spectrometry (LC-MS/MS). The samples were
      extracted with acetonitrile (1%, glacial acetic acid, v/v) and purified using
      primary secondary amine and octadecylsilane. The limit of detection was 0.01-0.13
      mg/kg, whereas that of quantification was 0.02-0.40 mg/kg for spirotetramat and
      its metabolites. The average recoveries of spirotetramat, spirotetramat-enol,
      spirotetramat-mono-hydroxy, spirotetramat-enol-glucoside and spirotetramat
      ketohydroxy in all matrices were 73.33-107.91%, 75.93-114.85%, 76.44-100.78%,
      71.46-103.19% and 73.08-105.27%, respectively, with relative standard deviations
      < 12.32%. The dissipation dynamics of spirotetramat in citrus and soil followed
      first-order kinetics, with half-lives of 2.3-8.5 days in the three sampling
      locations. The terminal residues of spirotetramat in four matrices at the three
      locations were measured below the 1.0 mg/kg maximum residue limit set by China,
      and residues were found to be concentrated on the peel. The risk assessment of
      citrus was evaluated using risk quotients. The risk quotient values were found to
      be significantly <1, suggesting that the risk to human health was negligible when
      using the recommended doses of spirotetramat in citrus. These results could
      provide guidance for the safe and proper application of spirotetramat in citrus
      in China.

PMID- 29169205
TI  - Mechanical cerebral thrombectomy in a BiVAD patient awaiting cardiac
      transplantation.

PMID- 29169204
TI  - Newborn genetic screening for spinal muscular atrophy in the UK: The views of the
      general population.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder
      and a leading genetic cause of infant death worldwide. However, there is no
      routine screening program for SMA in the UK. Lack of treatments and the inability
      of screening tests to accurately predict disease severity are among the key
      reasons implementation of screening has faltered in the UK. With the recent
      release of the first therapy for SMA (Nusinersen), calls are being made for a
      reconsideration of this stance; however, very little is known about the views of
      the general public. METHODS: An online survey was administered to 232 individuals
      with no prior relationship with SMA to assess their attitudes toward a newborn
      screening program for it. Results are compared with previously gathered data on
      the views of SMA-affected families toward screening. RESULTS: Eighty-four percent
      of participants were in favor of newborn screening. Key reasons for support were
      a belief that it would lead to better healthcare and life expectancy for affected
      infants and facilitate informed decision-making for future pregnancies. Key
      reasons for nonsupport were a belief in the potential for significant negative
      impact on the family unit in terms of bonding and stress. CONCLUSIONS: Public
      acceptability is a key component in the evaluation of any potential screening
      program in the UK. This study demonstrates that newborn screening for SMA is
      viewed largely positively by people unfamiliar with the condition. The importance
      of early identification overrode all other social and ethical concerns about
      screening for the majority of participants.

PMID- 29169206
TI  - Acute type A aortic dissection with occlusion of both carotid arteries: Direct
      carotid perfusion prior to aortic repair.

PMID- 29169207
TI  - Primary cardiac leiomyosarcoma causing severe pulmonary hypertension.

PMID- 29169208
TI  - The use of preoperative aspirin in cardiac surgery: The ruling on the field
      stands.

PMID- 29169209
TI  - Management of coronary artery obstruction following TAVR-The importance of the
      heart team approach.

PMID- 29169210
TI  - Ruptured coronary artery aneurysm with pulmonary artery fistulae.

PMID- 29169211
TI  - Simultaneous determination of kaempferol, quercetin, mangiferin, gallic acid, p
      hydroxybenzoic acid and chlorpheniramine maleate in rat plasma after oral
      administration of Mang-Guo-Zhi-Ke tablets by UHPLC-MS/MS and its application to
      pharmacokinetics.
AB  - Mang-Guo-Zhi-Ke tablets (MGZKTs) is an effective Chinese patent medicine. It
      contains mango leaf extract as the main raw material and the antihistamine drug,
      chlorpheniramine maleate is included in the formulation. However, its
      pharmacokinetic effect is rarely reported. A highly sensitive, reliable and rapid
      high-throughput method using ultra-high-performance liquid chromatography with
      tandem mass spectrometry (UHPLC-MS/MS) was used to simultaneously determine
      kaempferol, quercetin, mangiferin, p-hydroxybenzoic acid, gallic acid and
      chlorpheniramine maleate in rat plasma after oral administration of MGZKTs. The
      method was successfully developed and fully validated to investigate the
      pharmacokinetics of MGZKTs. Chloramphenicol and clarithromycin were used as
      internal standards (IS). A practicable protein precipitation procedure with
      methanol was adopted for sample preparation. The samples were separated on an
      Acquity UHPLC Syncronis C18 column (100 * 2.1 mm, 1.7 MUm) using 0.1% formic acid
      acetonitrile as the mobile phase. The flow rate was set at 0.4 mL/min. The
      obtained calibration curves were linear in the concentration range of ~1-1000
      ng/mL for plasma (r > 0.99). Method validation results met the criteria reported
      in the US Food and Drug Administration guidelines. Quercetin, p-hydroxybenzoic
      acid and kaempferol were absorbed rapidly and reached the peak concentration
      between 0.16 and 0.25 h. This validated that the UHPLC-MS/MS method was
      successfully applied to study the pharmacokinetic parameters of the six compounds
      in rat plasma after oral administration of MGZKTs. This evidence will be useful
      for the clinical rational use of Mang-Guo-Zhi-Ke tablets.

PMID- 29169212
TI  - Complications of CO2 insufflation during endoscopic vein harvesting.
AB  - Over the past few decades, the use of endoscopic harvest of the saphenous vein
      has gained popularity due to a significant reduction in rates of wound infection
      and improved cosmesis. The widespread adoption of this technique has introduced a
      set of complications associated with the use CO2 insufflation which facilitates
      exposure during the vein harvest. We describe a case of pneumoperitoneum with
      systemic acidosis and subcutaneous air following endoscopic vein harvest for
      coronary artery bypass grafting and review the complications that may arise from
      CO2 insufflation during endoscopic vein harvesting.

PMID- 29169213
TI  - The use of extracorporeal membrane oxygenation in type A aortic dissections-Long
      run for a short slide?

PMID- 29169215
TI  - Giant coronary artery aneurysm presenting as a right paracardial mass.

PMID- 29169214
TI  - Left ventricular myxoma associated with mitral regurgitation.

PMID- 29169216
TI  - CO2 insufflation during endoscopic vein harvesting-Surgeon beware!

PMID- 29169217
TI  - Complete Biotransformation of Protopanaxatriol-Type Ginsenosides in Panax ginseng
      Leaf Extract to Aglycon Protopanaxatriol by beta-Glycosidases from Dictyoglomus
      turgidum and Pyrococcus furiosus.
AB  - Aglycon protopanaxatriol (APPT) has valuable pharmacological effects such as
      memory enhancement and tumor inhibition. beta-Glycosidase from the
      hyperthermophilic bacterium Dictyoglomus turgidum (DT-bgl) hydrolyzes the glucose
      residues linked to APPT, but not other glycoside residues. beta-Glycosidase from
      the hyperthermophilic bacterium Pyrococcus furiosus (PF-bgl) hydrolyzes the outer
      sugar at C-6 but not the inner glucose at C-6 or the glucose at C-20. Thus, the
      combined use of DT-bgl and PF-bgl is expected to increase the biotransformation
      of PPT-type ginsenosides to APPT. We optimized the ratio of PF-bgl to DT-bgl, the
      concentrations of substrate and enzyme, and the reaction time to increase the
      biotransformation of ginsenoside Re and PPT-type ginsenosides in Panax ginseng
      leaf extract to APPT. DT-bgl combined with PF-bgl converted 1.0 mg/ml PPT-type
      ginsenosides in ginseng leaf extract to 0.58 mg/ml APPT without other
      ginsenosides, with a molar conversion of 100%. We achieved the complete
      biotransformation of ginsenoside Re and PPT-type ginsenosides in ginseng leaf
      extract to APPT by the combined use of two beta-glycosidases, suggesting that
      discarded ginseng leaves can be used as a source of the valuable ginsenoside
      APPT. To the best of our knowledge, this is the first quantitative production of
      APPT using ginsenoside Re, and we report the highest concentration and
      productivity of APPT from ginseng extract to date.

PMID- 29169219
TI  - Genome Analysis of Naphthalene-Degrading Pseudomonas sp. AS1 Harboring the
      Megaplasmid pAS1.
AB  - Polycyclic aromatic hydrocarbons (PAHs), including naphthalene, are widely
      distributed in nature. Naphthalene has been regarded as a model PAH compound for
      investigating the mechanisms of bacterial PAH biodegradation. Pseudomonas sp. AS1
      isolated from an arsenic-contaminated site is capable of growing on various
      aromatic compounds such as naphthalene, salicylate, and catechol, but not on
      gentisate. The genome of strain AS1 consists of a 6,126,864 bp circular
      chromosome and the 81,841 bp circular plasmid pAS1. Pseudomonas sp. AS1 has
      multiple dioxygenases and related enzymes involved in the degradation of aromatic
      compounds, which might contribute to the metabolic versatility of this isolate.
      The pAS1 plasmid exhibits extremely high similarity in size and sequences to the
      well-known naphthalene-degrading plasmid pDTG1 in Pseudomonas putida strain NCIB
      9816-4. Two gene clusters involved in the naphthalene degradation pathway were
      identified on pAS1. The expression of several nah genes on the plasmid was
      upregulated by more than 2-fold when naphthalene was used as a sole carbon
      source. Strains have been isolated at different times and places with different
      characteristics, but similar genes involved in the degradation of aromatic
      compounds have been identified on their plasmids, which suggests that the
      transmissibility of the plasmids might play an important role in the adaptation
      of the microorganisms to mineralize the compounds.

PMID- 29169218
TI  - Laccase Fermentation of Clove Extract Increases Content of Dehydrodieugenol,
      Which Has Neuroprotective Activity against Glutamate Toxicity in HT22 Cells.
AB  - Enzyme fermentation is a type of food processing technique generally used to
      improve the biological activities of food and herbal medicines. In this study, a
      Syzygii Flos (clove) extract was fermented using laccase derived from Trametes
      versicolor (LTV). The fermented clove extract showed greater neuroprotective
      effects against glutamate toxicity on HT22 than the non-fermented extract did.
      HPLC analysis revealed that the eugenol (1) and dehydrodieugenol (2) contents had
      decreased and increased, respectively, after fermentation. The content of 2
      peaked at 1 h after fermentation to 103.50 +/- 8.20 mg/gex (not detected at zero
      time), while that of 1 decreased to 79.54 +/- 4.77 mg/gex (185.41 +/- 10.16
      mg/gex at zero time). Compound 2 demonstrated promising HT22 neuroprotective
      properties with inhibition of Ca2+ influx, the overproduction of intracellular
      reactive oxygen species, and lipid peroxidation. In addition, LTV showed the best
      fermentation efficacy compared with laccases derived from Pleurotus ostreatus and
      Rhus vernicifera.

PMID- 29169220
TI  - Fermented Soymilk Alleviates Lipid Accumulation by Inhibition of SREBP-1 and
      Activation of NRF-2 in the Hepatocellular Steatosis Model.
AB  - Ingredients of soy and fermented soy products have been widely utilized as food
      supplements for health-enhancing properties. The aim of this study was to
      evaluate the effects of fermented soymilk (FSM) and soymilk (SM) on free fatty
      acid-induced lipogenesis in the hepatocellular steatosis model. HepG2 cells were
      incubated with palmitic acid (PA) for 24 h to induce lipogenesis and accumulation
      of intracellular lipid contents. The PA-treated cells were co-incubated with FSM,
      SM, genistein, and estrogen, respectively. Lipid accumulation in the PA-treated
      HpG2 cells was significantly decreased by co-incubation with FSM. Treatment of
      HepG2 cells with PA combined with genistein or estrogen significantly increased
      the expression of SREBP-1. However, FSM co-incubation significantly attenuated
      SREBP-1 expression in the PA-treated HepG2 cells; in addition, expression of NRF
      2 and phosphorylation of ERK were significantly increased in the PA and FSM co
      incubated cells. PA-induced ROS production was significantly reduced by FSM and
      SM. Our results suggested that the bioactive components of FSM could protect
      hepatocytes against the lipid accumulation and ROS production induced by free
      fatty acids. These effects may be mediated by the inhibition of SREBP-1 and the
      activation of NRF-2 via the ERK pathway in HepG2 cells.

PMID- 29169221
TI  - Biochemical Characterization of a Novel GH86 beta-Agarase Producing
      Neoagarohexaose from Gayadomonas joobiniege G7.
AB  - A novel beta-agarase, AgaJ5, was identified from an agar-degrading marine
      bacterium, Gayadomonas joobiniege G7. It belongs to the glycoside hydrolase
      family 86 and is composed of 805 amino acids with a 30-amino-acid signal peptide.
      Zymogram analysis showed that purified AgaJ5 has agarase activity. The optimum
      temperature and pH for AgaJ5 activity were determined to be 30 degrees C and 4.5,
      respectively. AgaJ5 was an acidic beta-agarase that had strong activity at a
      narrow pH range of 4.5-5.5, and was a cold-adapted enzyme, retaining 40% of
      enzymatic activity at 10 degrees C. AgaJ5 required monovalent ions such as Na+
      and K+ for its maximum activity, but its activity was severely inhibited by
      several metal ions. The Km and Vmax of AgaJ5 for agarose were 8.9 mg/ml and 188.6
      U/mg, respectively. Notably, thin-layer chromatography, mass spectrometry, and
      agarose-liquefication analyses revealed that AgaJ5 was an endo-type beta-agarase
      producing neoagarohexaose as the final main product of agarose hydrolysis.
      Therefore, these results suggest that AgaJ5 from G. joobiniege G7 is a novel endo
      type neoagarohexaose-producing beta-agarase having specific biochemical features
      that may be useful for industrial applications.

PMID- 29169222
TI  - Metagenomic Approach to Identifying Foodborne Pathogens on Chinese Cabbage.
AB  - Foodborne illness represents a major threat to public health and is frequently
      attributed to pathogenic microorganisms on fresh produce. Recurrent outbreaks
      often come from vegetables that are grown close to or within the ground.
      Therefore, the first step to understanding the public health risk of
      microorganisms on fresh vegetables is to identify and describe microbial
      communities. We investigated the phyllospheres on Chinese cabbage (Brassica rapa
      subsp. pekinensis, N = 54). 16S rRNA gene amplicon sequencing targeting the V5-V6
      region of 16S rRNA genes was conducted by employing the Illumina MiSeq system.
      Sequence quality was assessed, and phylogenetic assessments were performed using
      the RDP classifier implemented in QIIME with a bootstrap cutoff of 80%. Principal
      coordinate analysis was performed using a weighted Fast UniFrac matrix. The
      average number of sequence reads generated per sample was 34,584. At the phylum
      level, bacterial communities were composed primarily of Proteobacteria and
      Bacteroidetes. The most abundant genera on Chinese cabbages were
      Chryseobacterium, Aurantimonadaceae_g, Sphingomonas, and Pseudomonas. Diverse
      potential pathogens, such as Pantoea, Erwinia, Klebsiella, Yersinia, Bacillus,
      Staphylococcus, Salmonella, and Clostridium were also detected from the samples.
      Although further epidemiological studies will be required to determine whether
      the detected potential pathogens are associated with foodborne illness, our
      results imply that a metagenomic approach can be used to detect pathogenic
      bacteria on fresh vegetables.

PMID- 29169223
TI  - Comparison of PFGE, IS6110-RFLP, and 24-Locus MIRU-VNTR for Molecular
      Epidemiologic Typing of Mycobacterium tuberculosis Isolates with Known Epidemic
      Connections.
AB  - Two molecular epidemiologic methods, IS6110 restriction fragment length
      polymorphism (IS6110-RFLP) and 24-locus mycobacterial interspersed repetitive
      unit-variable-number tandem repeat (MIRU-VNTR), are used worldwide in studies of
      Mycobacterium tuberculosis (MTB). Conversely, because of its poor resolution,
      pulsed-field gel electrophoresis (PFGE) is not widely used for MTB. In this
      study, we improved the 24-locus MIRU-VNTR and PFGE protocols and compared the
      effectiveness of these approaches for the molecular typing of MTB using 75
      clinical isolates obtained from a cohort investigation of high-risk populations
      infected with MTB. The 24-locus MIRU-VNTR method demonstrated superior
      discriminatory ability, followed by PFGE and IS6110-RFLP. Next, we analyzed six
      isolates with clear epidemiologic connections; that is, isolates from patients
      who attended the same school. IS6110-RFLP and PFGE identified these samples as
      the same type. By contrast, according to MIRU-VNTR, two isolates differed from
      four other isolates at one locus each; one isolate was identified as Mtub29 and
      the other as QUB-26. In summary, the 24-locus MIRU-VNTR assay was the most useful
      molecular typing method among the three methods investigated due to its
      discriminatory power, short time required, and availability as an epidemiologic
      investigation tool. PFGE was the second-best method. Compared with the other loci
      assessed in the 24-locus MIRU-VNTR assay, the Mtub29 and QUB-26 loci appeared to
      exhibit greater variability during transmission.

PMID- 29169224
TI  - Epigenetic Control of Oxidative Stresses by Histone Acetyltransferases in Candida
      albicans.
AB  - Candida albicans is a major pathogenic fungus in humans, and meets at first the
      innate immune cells, such as macrophages, in its host. One important strategy of
      the host cell to kill C. albicans is to produce reactive oxygen species (ROS) by
      the macrophages. In response to ROS produced by the macrophages, C. albicans
      operates its defense mechanisms against them by expressing its oxidative stress
      response genes. Although there have been many research studies explaining the
      specific transcription factors and the expression of the oxidative stress genes
      in C. albicans, the regulation of the oxidative stress genes by chromatin
      structure is little known. Epigenetic regulation by the chromatin structure is
      very important for the regulation of eukaryotic gene expression, including the
      chromatin structure dynamics by histone modifications. Among various histone
      modifications, histone acetylation is reported for its direct relationship to the
      regulation of gene expression. Recent studies reported that histone
      acetyltransferases regulate genes to respond to the oxidative stress in C.
      albicans. In this review, we introduce all histone acetyltransferases that C.
      albicans contains and some papers that explain how histone acetyltransferases
      participate in the oxidative stress response in C. albicans.

PMID- 29169225
TI  - Comparison of the effects of isoflurane versus propofol-remifentanil anesthesia
      on oxygen delivery during thoracoscopic lung lobectomy with one-lung ventilation
      in dogs.
AB  - This study compared effects of isoflurane inhalation (ISO) and propofol
      remifentanil combined total intravenous anesthesia (TIVA) on oxygenation during
      thoracoscopic lung lobectomy with 30-min one-lung ventilation (1LV).
      Thoracoscopic right middle lung lobectomy was performed in ten dogs divided into
      ISO and TIVA groups, and cardiopulmonary parameters were measured with blood gas
      analysis. Throughout the study, isoflurane was inhaled up to 1.5%, and the
      infusion rates of propofol and remifentanil were 0.2 to 0.4 mg/kg/min and 6 to 11
      ug/kg/h, respectively. Cardiac index was not affected in the ISO group, but it
      increased during 1LV in the TIVA group. There were significant alterations in
      arterial oxygen pressure, arterial oxygen saturation, oxygen content, and shunt
      fraction associated with 1LV in each group. However, oxygen delivery did not
      decrease significantly due to open chest condition, 1LV, or surgical maneuver in
      either group, rather it increased during 1LV in the TIVA group. All parameters
      showed no significant difference between groups. Pulmonary vascular resistant
      index was unaffected in both groups, and there was no difference between groups
      except in re-ventilation phase. Accordingly, the effect of both anesthetic
      regimens on oxygenation was not different between groups and can be used with
      short-term 1LV for thoracoscopic lung lobectomy in dogs.

PMID- 29169226
TI  - Cytological endometritis in dairy cows: diagnostic threshold, risk factors, and
      impact on reproductive performance.
AB  - We determined the threshold proportion of polymorphonuclear leukocytes (PMNs) for
      a diagnosis of cytological endometritis (CEM), the risk factors for this
      condition, and its impact on reproductive performance in dairy cows. Uterine
      cytology was performed on 407 Holstein cows 4 weeks postpartum to determine the
      proportions of endometrial cells and PMNs. A receiver operator characteristics
      curve was used to determine the threshold above which the PMN proportion affected
      the likelihood of cows conceiving by 200 days postpartum. The optimal threshold
      was >= 14% PMN (sensitivity, 31.3%; specificity, 81.7%; p < 0.05). The farm
      identity, retained placenta (odds ratio [OR] = 1.87), and septicemic metritis (OR
      = 3.07) were risk factors for CEM (p < 0.05). Cows with CEM were less likely to
      resume cyclicity (OR = 0.58) and to conceive by 200 days postpartum (hazard ratio
      = 0.58). Cows with CEM tended (p < 0.1) to be less likely to become pregnant
      after their first insemination (OR = 0.65) and to require a greater number of
      inseminations per conception (2.3 vs. 2.2). In conclusion, a PMN threshold of 14%
      defined the presence of CEM at 4 weeks postpartum. The farm, retained placenta,
      and septicemic metritis were risk factors for CEM, which reduces subsequent
      reproductive performance.

PMID- 29169227
TI  - Korean red ginseng excitation of paraventricular nucleus neurons via non-N-methyl
      D-aspartate glutamate receptor activation in mice.
AB  - It has been reported that Korean red ginseng (KRG), a valuable and important
      traditional medicine, has varied effects on the central nervous system,
      suggesting its activities are complicated. The paraventricular nucleus (PVN)
      neurons of the hypothalamus has a critical role in stress responses and hormone
      secretions. Although the action mechanisms of KRG on various cells and systems
      have been reported, the direct membrane effects of KRG on PVN neurons have not
      been fully described. In this study, the direct membrane effects of KRG on PVN
      neuronal activity were investigated by using a perforated patch-clamp in ICR
      mice. In gramicidin perforated patch-clamp mode, KRG extract (KRGE) induced
      repeatable depolarization followed by hyperpolarization of PVN neurons. The KRGE
      induced responses were concentration- dependent and persisted in the presence of
      tetrodotoxin, a voltage sensitive Na+ channel blocker. The KRGE-induced responses
      were suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione (10 MUM), a non-N-methyl
      D-aspartate (NMDA) glutamate receptor antagonist, but not by picrotoxin, a type A
      gamma-aminobutyric acid receptor antagonist. The results indicate that KRG
      activates non-NMDA glutamate receptors of PVN neurons in mice, suggesting that
      KRG may be a candidate for use in regulation of stress responses by controlling
      autonomic nervous system and hormone secretion.

PMID- 29169228
TI  - Control of type O foot-and-mouth disease by vaccination in Korea, 2014-2015.
AB  - On December 3, 2014, a type O foot-and-mouth disease (FMD) outbreak began in
      Korea. Although vaccinations were administered, FMD cases increased steadily for
      five months, and reached 185 cases by April 2015. Most of the affected animals
      were pigs, which are vulnerable to vaccination. The FMD virus belonged to the
      South-East Asia (SEA) topotype that had been observed three times in Korea
      between April 2010 and July 2014. However, the FMD virus isolated in December
      2014 had a unique feature; that is, partial deletion of the 5' non-coding region,
      a deletion not seen in previous SEA topotype isolates identified in Korea. We
      conclude that this outbreak included the introduction of a new FMD strain to
      Korea, and that Korea was now affected by genetically similar FMD virus strains
      that are related to those from neighboring countries.

PMID- 29169229
TI  - Novel vertebral computed tomography indices in normal and spinal disorder dogs.
AB  - This study was carried out to derive and evaluate reference computed tomography
      (CT)-based indices for normal canine spine. CT and magnetic resonance images were
      acquired from 12 clinically normal Beagle dogs (normal group) and 50 dogs with 56
      spinal disorders (patient group). Image acquisition regions were cervical spine
      (C2-T1), thoracic spine (T1-T13), and lumbar spine (L1-L7). Measured indices
      were: the ratios of width to height of the spinal cord including the dura matter
      (CR) and of the vertebral foramen (FR), and the ratio of the cross-sectional area
      of the spinal cord to that of the vertebral foramen (CFAR). Reliability analysis
      was performed to evaluate intermodality agreement. Student's t-tests and receiver
      operating characteristic curves were used to discriminate the normal and patient
      groups on CT. Intermodality agreements of the normal and patient groups were
      acceptable to excellent. The highest discriminating levels of CR at the vertebral
      body level and the intervertebral disc space level were 1.25 or more and 1.44 or
      more, respectively. FR and CFAR had the highest discriminating level at the
      cervical region. This report presents quantitative information on canine spinal
      morphometry; the obtained indices may be helpful for CT screening of dogs with
      spinal disorders.

PMID- 29169230
TI  - Ultrasonographic features of pure ductal carcinoma in situ of the breast:
      correlations with pathologic features and biological markers.
AB  - PURPOSE: The purpose of this study was to evaluate the ultrasonographic features
      of pure ductal carcinoma in situ (DCIS) of the breast and to evaluate the
      correlations of ultrasonographic features with pathologic and biological
      features. METHODS: A total of 141 lesions in 138 women with pure DCIS who
      underwent preoperative breast ultrasonography were retrospectively reviewed.
      Ultrasonographic features were analyzed using the American College of Radiology
      Breast Imaging Reporting and Data System (BI-RADS) ultrasonography lexicon and
      the diagnostic criteria of the Japan Society of Ultrasonics in Medicine.
      Pathologic features including the nuclear grade and presence of comedonecrosis
      were evaluated. Biological markers including estrogen receptor, progesterone
      receptor, and human epidermal growth factor receptor 2 (HER2) status, as well as
      the Ki-67 index, were recorded. Ultrasonographic features were compared with
      pathologic findings and biological markers using the chi-square test. P-values of
      <0.05 were considered to indicate statistical significance. RESULTS: Of the 141
      lesions, 75 (53.2%) were mass lesions, 26 (39.7%) were non-mass lesions, and 10
      (7.1%) were not visible. The most common feature of the mass pattern was a mass
      with irregular shape (32.6%), an indistinct margin (27.7%), and hypoechogenicity
      (37.6%). Microcalcifications were observed in 48 cases (36.6%) as an associated
      feature. Calcifications outside of a mass were more common than calcifications
      within a mass. Ultrasonographic microcalcifications and ductal changes were
      frequently observed in non-mass lesions. Ultrasonographic non-mass lesions were
      associated with high-grade DCIS (P=0.004) and the presence of comedonecrosis
      (P=0.006), and microcalcifications were significantly associated with high-grade
      DCIS, the presence of comedonecrosis, an elevated Ki-67 index (P<0.001 for all),
      and HER2 positivity (P=0.003). CONCLUSION: The most common ultrasonographic
      feature of pure DCIS was an irregular, hypoechoic mass with an indistinct margin.
      Ultrasonographic microcalcifications and ductal changes were more frequent in non
      mass lesions, which were correlated with poor prognostic factors, such as a high
      nuclear grade, comedonecrosis, HER2 positivity, and an elevated Ki-67 index.

PMID- 29169231
TI  - Evaluating imaging-pathology concordance and discordance after ultrasound-guided
      breast biopsy.
AB  - Ultrasound (US)-guided breast biopsy has become the main method for diagnosing
      breast pathology, and it has a high diagnostic accuracy, approaching that of open
      surgical biopsy. However, methods for confirming adequate lesion retrieval after
      US-guided biopsy are relatively limited and false-negative results are
      unavoidable. Determining imaging-pathology concordance after US-guided biopsy is
      essential for validating the biopsy result and providing appropriate management.
      In this review article, we briefly present the results of US-guided breast
      biopsy; describe general aspects to consider when establishing imaging-pathology
      concordance; and review the various categories of imaging-pathology correlations
      and corresponding management strategies.

PMID- 29169232
TI  - Microcystic Stromal Tumor of Testicle: First Case Report and Literature Review.
AB  - Microcystic stromal tumor (MCST) is a rare subtype of sex cord-stromal neoplasm.
      Tumors from all 31 previously reported cases were located in the ovary. Herein,
      we present a unique case of a right-side testicular tumor in a 33-year-old
      Chinese male. The tumor is composed of predominantly lobulated cellular nodules
      separated by hyalinized fibrous stroma and they expressed CD10, beta-catenin
      (nuclear), and cyclin D1. Molecular analysis identified a point mutation
      (c.110C>G) in exon 3 of CTNNB1. The histopathological features,
      immunohistochemistry profiles, and molecular analysis of this tumor were
      consistent with MCST of the ovary. Therefore, a diagnosis of MCST of the right
      testicle was determined. To the best of our knowledge, this is the first case of
      MCST occurring in the testicles. The study may provide new insights to the tumor
      biology of MCST and a better understanding of this rare entity.

PMID- 29169234
TI  - Correction of the author name.
AB  - [This corrects the article on p. 178 in vol. 4.].

PMID- 29169233
TI  - Effect of Smoking Cessation and Reduction on the Risk of Cancer in Korean Men: A
      Population Based Study.
AB  - PURPOSE: The purpose of this study was to investigate the effect of smoking habit
      change on the risk of cancer. Materials and Methods: From the Korean National
      Health Insurance Service database, we determined the change in smoking habit
      between the first (2002 and 2003) and second (2004 and 2005) health examination
      periods. A total of 143,071 men were categorized into baseline heavy (>= 20
      cigarettes per day), moderate (10-19 cigarettes per day), light (< 10 cigarettes
      per day) smokers, quitters, and never smokers, after which the change in smoking
      status was determined during the second health examination. The participants were
      then followed up from 2006 to 2013 for all cancer, smoking related cancer, and
      lung cancer. RESULTS: Compared to heavy continual smokers, heavy smokers who quit
      had reduced risk of smoking related cancer (hazard ratio [HR], 0.74; 95%
      confidence interval [CI], 0.56 to 0.97) and tended to have reduced risk of all
      cancer (HR, 0.87; 95% CI, 0.75 to 1.00). Moderate smokers who reduced the amount
      of smoking to light levels had decreased risk of all cancer (HR, 0.82; 95% CI,
      0.72 to 0.94), smoking related cancer (HR, 0.74; 95% CI, 0.59 to 0.93), and lung
      cancer (HR, 0.55; 95% CI, 0.38 to 0.79) compared to heavy continual smokers.
      CONCLUSION: Smoking reduction decreases the risk of all cancer, smoking related
      cancer, and lung cancer. While smoking cessation should be the treatment of
      choice for smokers, smoking reduction may serve as an alternative strategy for
      those who cannot quit.

PMID- 29169235
TI  - Hypermagnesuria in Humans Following Acute Intravenous Administration of Digoxin.
AB  - BACKGROUND: Hypomagnesemia is a known predisposing condition for the appearance
      of digitalis toxicity. The detection of a genetic form of Mg urinary wasting with
      hypomagnesemia being caused by a mutation in the gamma subunit (FXYD2) of the
      Na,K-ATPase, the pharmacological target of Digoxin, prompted us to investigate
      whether Digoxin administration increases urinary Mg excretion. METHODS: Two
      groups of subjects, with rapid atrial fibrillation, received intravenous Digoxin
      (n = 9) or verapamil (n = 8), for heart rate control. During the following 4 h,
      blood and urinary creatinine, sodium, potassium, calcium, and magnesium levels
      were determined, and fractional excretion (Fex) values for Na, K, Ca, and Mg were
      calculated. RESULTS: In the Digoxin group, at 60 min Fex Mg rose from 3.07 +/-
      1.21 to 7.58 +/- 2.51% (an increase of 269 +/- 107% of baseline, p < 0.001), and
      at 240 min to 6.05 +/- 2.30% (204 +/- 56% of baseline, p < 0.01). No significant
      change was observed for Fex Na, Fex K, and Fex Ca. A striking correlation was
      found between individual values of Fex Mg and serum Digoxin concentration (r =
      0.678, p < 0.0001). No significant correlation was found between Fex Na or Fex K
      and serum Digoxin. A correlation of borderline significance was found between Fex
      Ca and serum Digoxin (r = 0.349, p = 0.073). CONCLUSIONS: The hypermagnesuric
      effect of acute Digoxin treatment is reminiscent of the effect of the missense
      mutation in FXYD2, which assumes that FXYD2 is a positive regulator of Na,K
      ATPase in the distal convoluted tubule (DCT). The borderline calciuric effect of
      Digoxin may point to an additional site of action, more proximal to the DCT, that
      is, the thick ascending limb.

PMID- 29169236
TI  - Aerosol Emissions from Great Lakes Harmful Algal Blooms.
AB  - In freshwater lakes, harmful algal blooms (HABs) of Cyanobacteria (blue-green
      algae) produce toxins that impact human health. However, little is known about
      the lake spray aerosol (LSA) produced from wave-breaking in freshwater HABs. In
      this study, LSA were produced in the laboratory from freshwater samples collected
      from Lake Michigan and Lake Erie during HAB and nonbloom conditions. The
      incorporation of biological material within the individual HAB-influenced LSA
      particles was examined by single-particle mass spectrometry, scanning electron
      microscopy with energy-dispersive X-ray spectroscopy, and fluorescence
      microscopy. Freshwater with higher blue-green algae content produced higher
      number fractions of individual LSA particles that contained biological material,
      showing that organic molecules of biological origin are incorporated in LSA from
      HABs. The number fraction of individual LSA particles containing biological
      material also increased with particle diameter (greater than 0.5 MUm), a size
      dependence that is consistent with previous studies of sea spray aerosol impacted
      by phytoplankton blooms. Similar to sea spray aerosol, organic carbon markers
      were most frequently observed in individual LSA particles less than 0.5 MUm in
      diameter. Understanding the transfer of biological material from freshwater to
      the atmosphere via LSA is crucial for determining health and climate effects of
      HABs.

PMID- 29169237
TI  - Janus Colloids toward Interfacial Engineering.
AB  - Janus colloids are functional particles consisting of two surfaces (or internal
      materials) with distinct physical or chemical properties in the same particle.
      Owing to their amphiphilic nature, Janus colloids composed of both hydrophilic
      and hydrophobic faces provide a powerful tool to generate functional surfaces and
      to manipulate the properties of interfaces. Amphiphilic Janus colloids have shown
      promising applications as particulate surfactants in oil/water separation, as
      interfacial compatibilizers in polymer blends, and as assembly blocks in robust
      coatings with unique wettability. In this Feature Article, we summarize recent
      advances in engineering interfaces by using Janus colloids.

PMID- 29169238
TI  - Electronic and Optical Properties of Pristine and Vertical and Lateral
      Heterostructures of Janus MoSSe and WSSe.
AB  - On the basis of electron-electron self-energy corrections, quasiparticle band
      structures of Janus MoSSe and WSSe are identified, and the excitonic effects are
      demonstrated to play a dominate role in the optical response. Combining together
      MoSSe and WSSe monolayers to form vertical heterostructures (VHTs) and lateral
      heterostructures (LHTs) rarely leads to a simple arithmetic sum of their
      properties, giving rise to novel and unexpected behaviors. In particular, Rashba
      polarization can be enhanced in VHTs due to improved out-of-plane electric
      polarity. In the case of LHTs, photoresponse and absorption coefficients show
      optical activity in a wide visible light range. It is of interest that both VHTs
      and LHTs reveal type-II band alignment, enabling the separation of excitons.
      Besides, grain boundaries (GBs) of large angle (60 degrees ) in Janus MoSSe due
      to chalcogen effects behave as one-dimensional (1D) metallic quantum wires,
      suggesting the possible formation of 1D electron or hole gas in such electronic
      heterostructures.

PMID- 29169239
TI  - Modification of Transition-Metal Redox by Interstitial Water in Hexacyanometalate
      Electrodes for Sodium-Ion Batteries.
AB  - A sodium-ion battery (SIB) solution is attractive for grid-scale electrical
      energy storage. Low-cost hexacyanometalate is a promising electrode material for
      SIBs because of its easy synthesis and open framework. Most hexacyanometalate
      based SIBs work with aqueous electrolyte, and interstitial water in the material
      has been found to strongly affect the electrochemical profile, but the mechanism
      remains elusive. Here we provide a comparative study of the transition-metal
      redox in hexacyanometalate electrodes with and without interstitial water based
      on soft X-ray absorption spectroscopy and theoretical calculations. We found
      distinct transition-metal redox sequences in hydrated and anhydrated
      NaxMnFe(CN)6.zH2O. The Fe and Mn redox in hydrated electrodes are separated and
      are at different potentials, leading to two voltage plateaus. On the contrary,
      mixed Fe and Mn redox in the same potential range is found in the anhydrated
      system. This work reveals for the first time how transition-metal redox in
      batteries is strongly affected by interstitial molecules that are seemingly
      spectators. The results suggest a fundamental mechanism based on three competing
      factors that determine the transition-metal redox potentials. Because most
      hexacyanometalate electrodes contain water, this work directly reveals the
      mechanism of how interstitial molecules could define the electrochemical profile,
      especially for electrodes based on transition-metal redox with well-defined spin
      states.

PMID- 29169240
TI  - Differential Reinforcement of Other Behaviors to Treat Challenging Behaviors
      Among Children With Autism: A Systematic and Quality Review.
AB  - This review summarizes the literature regarding differential reinforcement of
      other behaviors (DRO) to treat challenging behavior among children with autism
      spectrum disorder (ASD) and determines the quality of studies among the current
      literature according to the 2014 Council for Exceptional Children (CEC):
      Standards for Evidence-Based Practices in Special Education. Studies that focused
      on the use of DRO in the treatment of challenging behavior for individuals with
      ASD were included for systematic analysis. Forty-five studies were identified for
      inclusion in this review and were evaluated using the eight quality indicators
      described by the CEC. To the authors' knowledge, this is the only systematic
      review of the literature that evaluates DRO as an intervention for individuals
      diagnosed with ASD. Principle findings, practical recommendations, and areas of
      future research are discussed.

PMID- 29169242
TI  - Lag Schedules and Functional Communication Training: Persistence of Mands and
      Relapse of Problem Behavior.
AB  - We evaluated the effects of lag schedules of reinforcement and functional
      communication training (FCT) on mand variability and problem behavior in two
      children with autism spectrum disorder. Specifically, we implemented FCT with
      increasing lag schedules and compared its effects on problem behavior with
      baseline conditions. The results showed that both participants exhibited low
      rates of problem behavior during treatment relative to baseline during and
      following schedule thinning (up to a Lag 5 schedule arrangement). Variable and
      total mands remained high during schedule thinning. With one participant,
      variable manding persisted when the value of the lag schedule was reduced to
      zero. The current results are discussed in terms of implications for training
      multiple mand topographies during FCT for the potential prevention and/or
      mitigation of clinical relapse during challenges to treatment.

PMID- 29169243
TI  - Time Savings Using a Standardized Glucose Reporting System and Ambulatory Glucose
      Profile.
AB  - BACKGROUND: Diabetes care is predominately done at home by the patient. When
      clinics do not have a reliable, easy process for obtaining this patient data,
      clinical decisions must be made with incomplete verbal recall reports. Unused or
      inaccessible glucose data represent a large information gap affecting clinical
      decision making. This study's purpose was to design an optimized glucose device
      download system with a standardized report and to evaluate its efficiency.
      METHODS: Observations and evaluations of glucose data retrieval occurred at two
      clinics; an additional clinic utilized the optimized process doing only post
      process timings. Patients/families and clinicians were surveyed about their
      experiences with the system and the standardized report (AGP). The study was
      approved by all the sites' IRBs. RESULTS: Optimized systems saved staff at least
      3 min per patient. Standardized AGP reports and an optimized data system made the
      work flow of glucose data easier to complete. The AGP report was preferred by
      patients, families, and clinicians. CONCLUSIONS: An optimized system takes
      advantage of patient lobby downtime to download glucose devices and ensures that
      diabetes clinical decisions are made utilizing all available data. Staff and
      patients liked the software lobby system and found it a valuable time-saving
      tool.

PMID- 29169241
TI  - Gut reactions: How the blood-brain barrier connects the microbiome and the brain.
AB  - A growing body of evidence indicates that the microbiome interacts with the
      central nervous system (CNS) and can regulate many of its functions. One
      mechanism for this interaction is at the level of the blood-brain barriers
      (BBBs). In this minireview, we examine the several ways the microbiome is known
      to interact with the CNS barriers. Bacteria can directly release factors into the
      systemic circulation or can translocate into blood. Once in the blood, the
      microbiome and its factors can alter peripheral immune cells to promote
      interactions with the BBB and ultimately with other elements of the neurovascular
      unit. Bacteria and their factors or cytokines and other immune-active substances
      released from peripheral sites under the influence of the microbiome can cross
      the BBB, alter BBB integrity, change BBB transport rates, or induce release of
      neuroimmune substances from the barrier cells. Metabolic products produced by the
      microbiome, such as short-chain fatty acids, can cross the BBB to affect brain
      function. Through these and other mechanisms, microbiome-BBB interactions can
      influence the course of diseases as illustrated by multiple sclerosis. Impact
      statement The connection between the gut microbiome and central nervous system
      (CNS) disease is not fully understood. Host immune systems are influenced by
      changes to the microbiota and offers new treatment strategies for CNS disease.
      Preclinical studies provide evidence of changes to the blood-brain barrier when
      animals are subject to experimental gut infection or when the animals lack a
      normal gut microbiome. The intestine also contains a barrier, and bacterial
      factors can translocate to the blood and interact with host immune cells. These
      metastatic bacterial factors can signal T-cells to become more CNS penetrant,
      thus providing a novel intervention for treating CNS disease. Studies in humans
      show the therapeutic effects of T-cell engineering for the treatment of leukemia,
      so perhaps a similar approach for CNS disease could prove effective. Future
      research should begin to define the bacterial species that can cause immune cells
      to differentiate and how these interactions vary amongst CNS disease models.

PMID- 29169244
TI  - Translation and Validation of the Toronto Pain Management Index, French-Canadian
      Version.
AB  - Background To provide effective pain management, nurses must have sufficient
      knowledge and adequate beliefs about pain management. In Quebec, however, nurses
      seem to be generally uninvolved in pain management, and there is little
      significant evidence shedding light on nurses' pain management knowledge and
      beliefs in postoperative settings. To perform such studies, a valid questionnaire
      in French to assess nurses' knowledge and beliefs is required. Some valid
      questionnaires are available in English, but none are available in French.
      Purpose This article describes the process of translation, adaptation, and
      preliminary validation of the Toronto Pain Management Index into French. Results
      For temporal stability of the Toronto Pain Management Index, French-Canadian
      version, the result of intraclass correlation coefficient for the total score of
      this questionnaire is 0.59 (CI: 0.44-0.72). Conclusion Following this process,
      the French version of this questionnaire has suitable face and content validity
      and can be used to evaluate nurses' knowledge and beliefs about pain management
      in postoperative settings.

PMID- 29169245
TI  - A systematic review of evidence for older adults' sedentary behavior and physical
      activity after hip fracture.
AB  - OBJECTIVE: To synthesize evidence on older adults' sedentary behavior and
      physical activity during rehabilitation and recovery for hip fracture (1) across
      the care continuum and (2) from clinical interventions. DESIGN: We conducted a
      systematic review of peer-reviewed publications using CINAHL, Embase, Ovid
      MEDLINE, PsycINFO, and SportDiscus (last search: 17 October 2017). STUDY
      SELECTION: We included studies that measured sedentary behavior and physical
      activity of older adults with hip fracture using activity monitors (e.g.
      accelerometers). We identified literature at Level 1 (title and abstract) and
      Level 2 (full text), and conducted forward and backward searches. We assessed
      observational studies' adherence to reporting guidelines and intervention
      studies' risk of bias. RESULTS: We included 14 studies (882 participants). Four
      studies reported sedentary behavior data, while all studies reported information
      on physical activity. Settings included hospital, rehabilitation centers, and the
      community. Nine studies were observational; five were experimental design. Older
      adults had excessive sedentary time (>10 hours/day) and low physical activity.
      Participants' average upright time differed across settings. During hospital
      stay, it ranged 16-52 minutes/day, while in the community, it ranged 51-261
      minutes/day. Data from five interventions reported on physical activity change:
      two studies increased between 14 and 27 minutes/day. Another study reported
      participants accumulated 6994 steps/day at the end of the intervention, but for
      two other interventions, activity was below 5000 steps/day. CONCLUSION: Based on
      available evidence, older adults with hip fracture engage in prolonged sedentary
      behavior and have low levels of physical activity during rehabilitation and
      recovery.

PMID- 29169246
TI  - Children With Intellectual Disability and Hospice Utilization: The Moderating
      Effect of Residential Care.
AB  - BACKGROUND: Children with intellectual disability commonly lack access to
      pediatric hospice care services. Residential care may be a critical component in
      providing access to hospice care for children with intellectual disability.
      OBJECTIVE/HYPOTHESIS: This research tested whether residential care intensifies
      the relationship between intellectual disability and hospice utilization (ie,
      hospice enrollment, hospice length of stay), while controlling for demographic
      characteristics. METHODS: Multivariate regression analyses were conducted using
      2008 to 2010 California Medicaid claims data. RESULTS: The odds of children with
      intellectual disability in residential care enrolling in hospice care were 3
      times higher than their counterparts in their last year of life, when controlling
      for demographics. Residential care promoted hospice enrollment among children
      with intellectual disability. The interaction between intellectual disability and
      residential care was not related to hospice length of stay. Residential care did
      not attenuate or intensify the relationship between intellectual disability and
      hospice length of stay. CONCLUSIONS: The findings highlight the important role of
      residential care in facilitating hospice enrollment for children with
      intellectual disability. More research is needed to understand the capability of
      residential care staff to identify children with intellectual disability earlier
      in their end-of-life trajectory and initiate longer hospice length of stays.

PMID- 29169247
TI  - Palliative Care Consultation for Goals of Care and Future Acute Care Costs: A
      Propensity-Matched Study.
AB  - BACKGROUND: Hospitals are under increasing pressure to manage costs across
      multiple episodes of care. Most studies of the financial impact of palliative
      care have focused on costs during a single hospitalization. OBJECTIVE: To compare
      future acute health-care costs and utilization between patients who received
      inpatient palliative care consultation for goals of care (Palliative Care Service
      [PCS]) and a propensity-matched cohort of patients who did not receive palliative
      care consultation (non-PCS) in a single academic medical center. METHODS: Data
      were extracted from the hospital's electronic records for admissions and
      discharges between July 2014 and October 2016. A stratified propensity score
      matching was used to account for nonrandom assignment and potential inherent
      differences between PCS and non-PCS groups using variables of theoretical
      interest: age, gender, race, diagnosis, risk of mortality, and prior acute care
      costs. RESULTS: The analytical sample for this study included 41 363 patients
      (PCS = 1853; non-PCS = 39 510). Future acute care costs were significantly higher
      in the non-PCS group after propensity score matching (highest tier = US$15 654 vs
      US$8831; second highest tier = US$12 200 vs US$5496; P = .0001). The non-PCS
      group also had significantly higher future acute care utilization across all
      propensity tiers and outcomes including 30-day readmission ( P = .0001), number
      of future hospital days ( P = .0001), and number of future intensive care unit
      days ( P = .0001). CONCLUSION: Palliative care consultations for goals of care
      may decrease future health-care utilization with cost savings that persist into
      future hospitalizations.

PMID- 29169248
TI  - Quality of Life and Compassion Satisfaction in Clinicians: A Pilot Intervention
      Study for Reducing Compassion Fatigue.
AB  - BACKGROUND: Compassion fatigue (CF) is prevalent in healthcare professionals,
      particularly in those caring for chronic, acutely ill, and/or those patients who
      might be moving toward comfort care. Over time, CF can lead to burnout (BO) and
      secondary traumatic stress and an overall decrease in professional quality of
      life. In this pilot study, participants completed a resiliency program focused on
      education about CF and self-awareness of its individualized impact and were
      expected to develop ongoing self-care practices to prevent/address the untoward
      effects. METHODS: Healthcare professionals ( N = 15) participated in a formalized
      educational program consisting of three 90-minute educational sessions held 2
      weeks apart. Preassessment and postintervention data were collected
      electronically in survey format. A postprogram evaluation was also offered.
      RESULTS: Upon completion of the program, participants noted an increase in
      compassion satisfaction (CS) and a small reduction in BO. Secondary traumatic
      stress remained unchanged. Feedback about the program was positive, and
      participants reported the impact on their clinical practice and life to be
      moderately high. At 6 months, over half of the participants continued to report
      positive impact on their personal/professional lives. CONCLUSION: While the small
      sample size of this pilot study limits the generalizability of the findings,
      there were positive effects for CS and BO in participants over time, indicating
      possible benefits of providing self-care education to healthcare providers.
      Additional research with a larger sample size is needed to address how healthcare
      providers might further benefit from resiliency education and interventions to
      improve professional quality of life.

PMID- 29169249
TI  - An intelligent detection method for high-field asymmetric waveform ion mobility
      spectrometry.
AB  - In conventional high-field asymmetric waveform ion mobility spectrometry signal
      acquisition, multi-cycle detection is time consuming and limits somewhat the
      technique's scope for rapid field detection. In this study, a novel intelligent
      detection approach has been developed in which a threshold was set on the
      relative error of alpha parameters, which can eliminate unnecessary time spent on
      detection. In this method, two full-spectrum scans were made in advance to obtain
      the estimated compensation voltage at different dispersion voltages, resulting in
      a narrowing down of the whole scan area to just the peak area(s) of interest.
      This intelligent detection method can reduce the detection time to 5-10% of that
      of the original full-spectrum scan in a single cycle.

PMID- 29169250
TI  - Clinical effects of cognitive impairment in patients with chronic obstructive
      pulmonary disease.
AB  - The aim of this study was to evaluate the clinical effects of cognitive
      impairment in patients with chronic obstructive pulmonary disease (COPD). A total
      of 91 patients with stable moderate to very severe COPD were included in this
      study. Cognitive functions of the patients were evaluated using the mini-mental
      state examination (MMSE) tool and clock-drawing test. The Brody's Instrumental
      Activities of Daily Living (IADL) Questionnaire; COPD assessment test (CAT); body
      mass index, airflow obstruction, dyspnea, and exercise capacity (BODE); and
      Charlson comorbidity index were assessed. The patients were divided into two
      groups as those who were diagnosed with cognitive impairment (group 1, n = 16)
      and those with normal cognitive functions (group 2, n = 75). Group 1 had a lower
      arterial partial pressure of oxygen , shorter 6-min walking distance, and higher
      arterial partial pressure of carbon dioxide (PaCO2) than group 2 ( p = 0.01, p =
      0.024, p = 0.018, respectively). In group 1, the IADL score was lower, and CAT
      and BODE scores were higher than group 2 ( p = 0.002, p = 0.037, p = 0.012,
      respectively). When we considered all the patients, there was an independent
      correlation between the IADL score and MMSE score ( p = 0.03). This study
      revealed that COPD patients with cognitive impairment may have more hypoxemia and
      limited activities of daily living.

PMID- 29169252
TI  - Distinguishing Levels of Suicide Risk in Depressed Male Veterans: The Role of
      Internalizing and Externalizing Psychopathology as Measured by the MMPI-2-RF.
AB  - Suicide occurs at high rates among veterans, underscoring a need for improved
      identification of veterans at risk of engaging in suicidal behavior. Considering
      dimensions of psychopathology in the context of an ideation-to-action framework,
      the present study examined the utility of the Minnesota Multiphasic Personality
      Inventory-2-Restructured Form in distinguishing depressed, psychiatrically
      hospitalized male veterans ( N = 430) at varying levels of suicide risk. Analysis
      of variance and hierarchical logistic regression analyses indicated that
      internalizing scales differentiated depressed ideators ( n = 147) and depressed
      controls ( n = 143); and in line with expectations, both broad and narrowly
      focused externalizing scales provided incremental validity in distinguishing
      depressed attempters ( n = 140) from depressed ideators. Interactions between
      Suicidal/Death Ideation and externalizing scale scores were found to
      differentiate only depressed ideators from depressed controls. Clinical
      implications in the areas of suicide risk assessment and therapeutic
      interventions with suicidal veterans are discussed.

PMID- 29169251
TI  - Factors Associated With Meat Safety Knowledge and Practices Among Butchers of
      Ratnanagar Municipality, Chitwan, Nepal: A Cross-sectional Study.
AB  - Butchers have a huge role in prevention of meat-borne diseases and illness.
      Hence, this study was conducted to ascertain factors associated with meat hygiene
      among the butchers. A cross-sectional study was conducted among goat and poultry
      butchers. None of the butchers fall into "adequate" knowledge and "good" practice
      category. Butchers who had no side job other than butchering (adjusted odds ratio
      [aOR] = 3.04, CI = 1.11-8.33), had secondary or higher education (aOR = 3.17, CI
      = 2.60-14.72), greater workload (aOR = 5.45, CI = 1.01-29.57), and whose shop
      were closed shop (aOR = 3.33, CI = 1.10-10.38) were more likely to have fair
      knowledge. Butchers whose shop were temporarily constructed close shop (aOR =
      3.07, CI = 1.04-9.06), permanently constructed close shop (aOR = 23.56, CI = 1.91
      291.11), and whose ethnicity was Brahmin/Chhetri (aOR = 3.39, CI = 1.10-10.46)
      were more likely to have satisfactory practices. Despite regular handling of
      meat, butchers had lack of knowledge and practice on meat hygiene.

PMID- 29169253
TI  - Treatment of Elopement Without Blocking With a Child With Autism.
AB  - Elopement is a dangerous behavior common in children with autism spectrum
      disorder (ASD). Relative to other forms of problematic behavior, elopement has
      received little attention in both assessment and treatment. The current study
      entailed a functional analysis of elopement of one child with ASD, results of
      which suggested a partially automatic function. We then evaluated a differential
      reinforcement procedure, along with a rule, which successfully decreased
      elopement without the use of blocking. A changing-criterion design embedded
      within a withdrawal design was used to gradually increase the criterion for
      maintaining a close proximity to a therapist prior to being allowed to run.

PMID- 29169254
TI  - Risky wandering behaviors of persons with dementia predict family caregivers'
      health outcomes.
AB  - OBJECTIVES: To examine the relationships between dementia persons' risky
      wandering behaviors and family caregivers' physical and mental health. METHODS: A
      secondary analysis was conducted using the original cross-sectional data from180
      dyads. The Risky Wandering and Adverse Outcome model assessed behaviors of
      eloping and getting lost outside the house for dementia persons. Data were
      analyzed using descriptive statistics, Pearson's correlation coefficient and
      hierarchical regressions. RESULTS: The mean age of caregivers was 56.01 years (SD
      = 13.8); 65% were female. Younger caregivers experienced greater physical fatigue
      and sleep disturbance. Presence of foreign helpers predicted a reduction in
      mental and physical fatigue of caregiver (beta = -0.186, p < .05; beta = 0.198, p
      < .05, respectively). Getting lost outside of the house influenced caregivers'
      mental fatigue (beta = 0-0.215, p < .05); eloping behavior influenced caregivers'
      sleep disturbance (beta = 0.231, p < .05). Care-receivers' activities of daily
      living affected caregivers' depressive symptoms (beta = -0.179, p < .05).
      CONCLUSIONS: Dementia family caregiver physical and mental health problems have
      distinct predictors. Employing the Risky Wandering and Adverse Outcome model
      could inform policy makers regarding long-term care resources to improve dementia
      care.

PMID- 29169255
TI  - A Standard-Setting Body for US Health Care Quality Measurement.

PMID- 29169256
TI  - Tolosa-Hunt Syndrome: Appraising the ICHD-3 beta diagnostic criteria.
AB  - Introduction The term Tolosa-Hunt Syndrome was first used more than half a
      century ago to describe painful ophthalmoplegia accompanied by cranial nerve
      palsies. In the decades since, its diagnostic criteria have evolved considerably.
      The beta version of the 3rd Edition of the International Classification of
      Headache Disorders narrows these criteria to require the demonstration of
      granulomatous inflammation on MRI or biopsy. We believe this may introduce
      challenges to accurate diagnosis. Discussion Requiring the demonstration of
      granulomatous inflammation for a diagnosis of Tolosa-Hunt Syndrome may introduce
      the potential for false negative and false positive diagnoses. Although the
      disorder presents secondary to granulomatous inflammation, MRI technology may not
      be able to identify it reliably, and biopsy is not always indicated for its
      symptomatology. Additionally, several cases have been reported of Tolosa-Hunt
      Syndrome diagnosed with MRI-confirmed granulomatous inflammation that later prove
      to be attributable to other pathologies. The emphasis on neuroimaging may
      therefore exclude some true Tolosa-Hunt Syndrome cases and include others
      resulting from other latent pathologies that are not visible on MRI. Conclusion
      We wish to offer several potential modifications to the International
      Classification of Headache Disorders guidelines for Tolosa-Hunt Syndrome,
      including making the demonstration of granulomatous inflammation on MRI or biopsy
      non-mandatory and lengthening patient follow-up to two years for cases in which
      MRI is unrevealing.

PMID- 29169257
TI  - Evaluation of the analytical and clinical performance of the Fujirebio
      Lumipulse(r) G 25-OH vitamin D assay.

PMID- 29169258
TI  - High-sensitivity cardiac troponin concentrations at emergency department
      presentation in females and males with an acute cardiac outcome.
AB  - Background There is interest in utilizing different cut-offs per sex for high
      sensitivity cardiac troponin I (hs-cTnI) but less so for high-sensitivity cardiac
      troponin T (hs-cTnT) for patient management in the acute setting. Our objective
      was to assess if differences in hs-cTn concentrations exist between males and
      females for an acute cardiac outcome following the presentation measurement in
      the emergency department. Methods An observational emergency department
      population with hs-cTn measurements (Roche Diagnostics and Abbott Diagnostics) at
      presentation with seven-day outcomes for a composite acute cardiac outcome (i.e.
      myocardial infarction, unstable angina, ventricular arrhythmia, heart failure or
      cardiovascular death) (ClinicalTrials.gov: NCT01994577). Receiver operating
      characteristic curve analyses were performed for each sex with both hs-cTn
      assays. Results In those patients who had a composite acute cardiac outcome ( n =
      128 females; n = 145 males), there was no difference in hs-cTn concentrations
      between the sexes (median [IQR] female hs-cTnT = 35 ng/L [21-69] vs. male hs-cTnT
      = 38 ng/L [19-77], P = 0.95; and median [IQR] female hs-cTnI = 27 ng/L [12-75]
      vs. male hs-cTnI = 26 ng/L [12-85], P = 0.97]. There was also no difference in
      the area under the curve between the hs-cTn assays and between the sexes ( P >
      0.10). Comparing hs-cTn concentrations in those patients with the composite
      outcome between the sexes <60 years and >=60 years of age also did not yield
      significant differences ( P > 0.70). Conclusions The concentrations and area
      under the curves of hs-cTnT and hs-cTnI at patient presentation in the emergency
      department for an acute composite cardiac outcome were similar between the sexes
      in this exploratory study.

PMID- 29169259
TI  - Assessing biomarker status of vitamin B12 in the laboratory: no simple solution.

PMID- 29169260
TI  - The psychiatry ashes: It's not cricket!

PMID- 29169261
TI  - This month: What is going on?

PMID- 29169262
TI  - Correction to: Amyloid (IAMY), Vol. 24, No. 4, 2017.

PMID- 29169263
TI  - The Development of Conformity Among Chinese Children Aged 9-15 Years in a Public
      Choice Task.
AB  - Both children and adults exhibit moderate conformity behaviors when facing group
      pressure. While some studies purport that children conform more with age, others
      have shown the opposite. The publicity of decision-making might be a major factor
      influencing the development of children's conformity behavior. In this study, we
      recruited 295 Chinese children aged 9-15 years. We observed no significant
      correlation between children's age and conformity behaviors when their answers
      were kept confidential. However, older children showed stronger conformity
      behaviors when their answers were made public. According to cultural evolutionary
      theory, with age, children find group acceptance and social recognition
      increasingly more important, which explains why older children are more likely to
      conform-namely, doing so has adaptive value. Further research should explore the
      cross-cultural coherence of this phenomenon and the genuine motivation behind
      children's conformity behaviors. Meanwhile, designing a more reliable and valid
      experiment would also be a fruitful direction.

PMID- 29169264
TI  - Adaptive Memory: Remembering Potential Mates.
AB  - According to the adaptive memory perspective, memory should function more
      efficiently in fitness-relevant domains. The current work explored whether there
      is a mnemonic tuning in a fundamental domain for human evolution: reproduction.
      In two experiments, female participants assessed how desirable potential male
      candidates (represented by a face and a short descriptor) would be in the context
      of a long-term mating relationship or in the context of a long-term work
      relationship. Then, after a short distractor task, participants performed a
      recognition task for the faces and a source memory task. Finally, they were asked
      to recall the descriptors presented during encoding. Experiment 1 used a between
      subjects design, whereas Experiment 2 employed a within-subject design. In both
      experiments, participants remembered the faces best when they were encoded in the
      mating condition. Also, in Experiment 1, source memory performance was better in
      the mating condition than in the working condition with the reverse being true
      for free recall of the descriptors. The latter difference was not observed in
      Experiment 2. These results suggest a potential mnemonic tuning for the faces of
      potential mate partners.

PMID- 29169265
TI  - A new formylated chalcone from Humulus lupulus with protective effect on HUVECs
      injury by angiotensin II.
AB  - One new formylated chalcone, 3'- formyl xanthohumol (1) was isolated from the
      EtOAc-soluble partition of the cones of Humulus lupulus, along with two other
      known chalcones, namely dehydrocycloxanthohumol (2) and xanthohumol (3). The
      structure of compound 1 was elucidated on the basis of its 1D, 2D NMR and MS
      data. The structures of the known compounds were identified by comparison of
      their spectroscopic data with those reported by the literatures. The isolates
      were tested for their protective effects on human umbilical vein endothelial
      cells (HUVECs) injured by angiotensin II (Ang II), all the three compounds
      protected against the cell injury at the concentration of 20 MUMU, and compound 3
      showed the most potent activity by improving cell viability from 53.9 to 74.9%.

PMID- 29169266
TI  - Microscale's relationship between Young's modulus and tissue density. Prediction
      of displacements.
AB  - The study presents an experimental verification of Wagner et al.'s relationship
      in microscale and proposes a modification of this relationship. For this purpose,
      11 cubic specimens were microcomputed tomography scanned and mechanically tested
      with the displacement full-field measurements using a digital image correlation
      system. Then, numerical simulations of the compression tests were performed using
      a finite elements method. The Young's modulus distributions assigned to the
      finite elements models were calculated using both of Wagner et al.'s
      relationships: original and modified. Comparison of the experimental and
      numerical results indicated the accuracy of numerical solutions for both
      relationships.

PMID- 29169267
TI  - Effect of pear apple and date fibres incorporation on the physico-chemical,
      sensory, nutritional characteristics and the acceptability of cereal bars.
AB  - Cereal bars are nutritious food composed of several ingredients including dry raw
      and agglutinative ingredients. The objective of this study was to evaluate the
      effect of pear apple and date fibres, from cooked fruit co-product, addition on
      the physico-chemical textural and sensory properties of cereal bars. First, five
      formulations containing an amount of 10% of co-products and commercial fibre,
      used as a reference, were elaborated and their physico-chemical composition was
      determined. Second, to determine the acceptability of consumer, apple fibre co
      products were added (6, 10 and 14%). Products were evaluated for their texture
      using a texturometer and sensory characteristics using an acceptance test.
      Results showed that physico-chemical composition of cereal bars elaborated with
      co-products was slightly different compared to those elaborated with commercial
      fibre. All bars have low water activity levels (~0.470) and interesting energy
      (300 kcal/100 g bar). External appearance revealed a darker colour
      (L*:~42/a*:~8/b*:~20). There were no significant differences (P > 0.05) in
      texture values (hardness: 40.8 N; cohesiveness: 0.34; springiness: 0.60;
      chewiness: 8.30 N) between cereal bars prepared with pear co-product and wheat
      bran. Acceptance test confirms the formulation used for cereals bars and showed
      that incorporation of 10% of co-product produced cereal bars with the highest
      acceptability. Sensory characteristics revealed that appearance is the limiting
      factor for consumer acceptability, essentially for cereal bars containing pear co
      product. Apple, pear and date co-products could be used successfully as a food
      ingredient to develop new formulations of cereal bars.

PMID- 29169268
TI  - Contamination sources, biofilm-forming ability and biocide resistance of
      Staphylococcus aureus in tilapia-processing facilities.
AB  - The major contamination sources, biofilm-forming ability and biocide resistance
      of Staphylococcus aureus in tilapia-processing plants were evaluated. Twenty-five
      processing control points were analysed twice in two factories, including whole
      tilapias, frozen fillets, water and food-contact surfaces. No final product was
      contaminated with S. aureus. However, high concentrations of S. aureus carrying
      enterotoxin ( se) genes were found in several processing points of both factories
      due to the application of inadequate hygienic and handling procedures, which
      generate a high risk of cross-contamination of the tilapia fillets with
      staphylococcal enterotoxins. Nine S. aureus strains were characterized by RAPD
      PCR using primers AP-7, ERIC-2 and S. A wide diversity of se gene profiles was
      detected, most strains being multi- se-carriers. All S. aureus strains showed
      high biofilm-forming ability on stainless steel and polystyrene. Biofilm-forming
      ability was correlated with the presence of fliC H7 and the type of origin
      surface (metallic or plastic). A marked resistance of S. aureus to peracetic acid
      and sodium hypochlorite was also observed, required doses being higher than those
      recommended by manufacturers to be eradicated. Case-by-case approaches are thus
      recommended to determine the sources and degree of contamination present in each
      factory, which would allow applying precise responses that avoid, or at least
      reduce, the presence of bacterial pathogens and the emergence of antimicrobial
      resistance.

PMID- 29169269
TI  - YAP regulates liver size and function.

PMID- 29169270
TI  - Nudging Healthier Choices in a Hospital Cafeteria: Results From a Field Study.
AB  - More than two thirds of adults and one third of children are overweight or obese
      in the United States. These trends have led to initiatives to provide information
      that supports informed choices. Traffic light labeling has been shown to increase
      consumer awareness and encourage healthy selections. This article contributes to
      the literature on healthy choices by comparing the additional contribution of a
      number of interventions used in combination with traffic light labeling. We
      conducted a 21-month field study in a workplace cafeteria. We analyzed cash
      register receipts, focusing on sales of beverages and chips. We found that the
      traffic light system was effective. The addition of caloric information to
      traffic light labeling had a positive effect on the purchase of healthy chips.
      However, other interventions appeared to produce more harm than good, essentially
      wiping out the benefits from traffic light labeling. These findings suggest that
      although it is possible to improve on traffic light labeling with selective
      interventions, caution is in order as some interventions may trigger compensatory
      behavior that results in the purchase of unhealthy items.

PMID- 29169271
TI  - Differentiation of mesenchymal stem cells into neuron-like cells using composite
      3D scaffold combined with valproic acid induction.
AB  - The nervous system has little capacity for self-repair after injury because
      neurons cannot proliferate owing to lack of suitable microenvironment. Therefore,
      neural tissue engineering that combines neural stem, scaffolds, and growth
      factors may improve the chance of restoration of damaged neural tissues. A
      favorable niche for neural regeneration would be both fibrous and electrically
      conductive scaffolds. Human Wharton jelly-derived mesenchymal stem cells were
      seeded on wet-electrospun 3D scaffolds composed of poly lactic acid coated with
      natural polymers including alginate and gelatin, followed by a multi-wall carbon
      nanotube coating. The results show that a wet-electrospun poly lactic acid
      scaffold at a concentration of 15% w/v had higher porosity (above 80%) than other
      concentrations. Moreover, the coated scaffold supported the growth of human
      Wharton jelly-derived mesenchymal stem cells in 3D culture, and were incubated
      for 21 days with 1 mM valproic acid as the inducer resulted in improvement in
      human Wharton jelly-derived mesenchymal stem cells differentiation into neuron
      like cells immunoreactivity to nestin, Map2, and neuron specific enolase (NSE),
      which were also consistent with reverse transcription polymerase chain reaction
      (RT-PCR) and quantitive Reverse transcription polymerase chain reaction (qRT-PCR)
      results. The conclusion is that the 3D composite nanofiber poly lactic acid
      scaffold improved the transdifferentiation of human Wharton jelly-derived
      mesenchymal stem cells into neuron-like cells.

PMID- 29169272
TI  - A Case of Benign Phyllodes Tumor in a Transgender Woman Receiving Cross-Sex
      Hormones.
AB  - Phyllodes tumor is a relatively uncommon fibroepithelial neoplasm of the breast
      characterized by proliferation of both stromal and epithelial elements. Benign
      phyllodes tumors are distinguished from fibroadenomas by their prominent leaf
      like architecture and exaggerated intracanalicular stromal growth pattern.
      Typically, these lesions affect older natal females; however, we present what we
      believe is the first reported case of benign phyllodes tumor in a hormonally
      treated transgender woman.

PMID- 29169273
TI  - Evaluating the Implementation of a Farmers' Market Targeting WIC FMNP
      Participants.
AB  - The present study planned and implemented a new farmers' market (FM) at a WIC
      (Special Supplemental Nutrition Program for Women, Infants, and Children) clinic
      in North Carolina, of which WIC FM Nutrition Program (FMNP) participants were the
      main priority population. The purpose of this FM was to provide convenience and
      improve access to locally grown fresh fruits and vegetables in the community and
      to increase the FMNP coupon redemption rate. The main objective of this study was
      to describe the overall process and key strategies involved in implementing a FM
      at a WIC clinic. A community-based participatory research design using different
      formative methods documented the process and key inputs in FM implementation.
      Local farmers, program administrators, and community advocates were involved in
      documenting the implementation process. Multiple formative methods included
      direct observation and semistructured interviews with staff and farmers (n = 13).
      A community partnership was key in implementing the FM. The market operated
      weekly over the course of 24 weeks, involved 12 WIC-approved farmers, and
      featured over 50 types of fresh fruits and vegetables. The FMNP coupon redemption
      rate at the county level increased from 51.3% to 62.9%. The results demonstrate
      that a FM can be successfully located near a WIC clinic with positive effects of
      increasing availability to fresh fruits and vegetables for a low-income
      population and revenue for local farmers.

PMID- 29169274
TI  - Replication checkpoint-mediated symmetric DNA synthesis: beginning to understand
      mechanism.

PMID- 29169275
TI  - Functionalised nanomaterials for eradication of CSCs, a promising approach for
      overcoming tumour heterogeneity.
AB  - Today, intratumoural heterogeneity has been recognised as one of the main causes
      of cancer treatment failure and drug resistance development through which
      multiple mechanisms are simultaneously involved. From the broad diversity of
      cells presented in tumour microenvironment, owing to their proliferative
      potential and longevity, cancer stem cells (CSCs), are the main cell
      subpopulation involved in tumour development, propagation, metastatic
      dissemination and induction of intratumoural heterogeneity. Accordingly,
      selective targeting and eradication of CSCs may represent a promising approach
      for cancer therapy and evading drug resistance development. Nanotechnology is an
      attractive outgrowing field in medicine due to its promising capabilities in
      solving several obstacles associated with conventional chemotherapy agents
      including poor solubility, lack of selectivity and high systemic toxicity.
      Accordingly, multiple types of nanocarriers have been successfully developed for
      improving selective delivery and reducing non-selective toxicities of CSC
      specific chemotherapy agents. In Current review, we mostly focus on examining the
      role of CSCs in development of intratumoral heterogeneity and introducing
      recently developed nano delivery systems for more efficient targeting and
      eradication of them.

PMID- 29169276
TI  - Iatrogenic Kaposi's Sarcoma in an HIV-Negative Young Male With Crohn's Disease
      and IgA Nephropathy: A Case Report and Brief Review of the Literature.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is a vascular tumor arising in association with
      human herpesvirus-8 (HHV-8) infection, and different variants show different
      clinical presentations. Isolated intestinal KS in the background of Crohn's
      disease (CD) is exceedingly rare with only 3 cases reported in the English
      literature (from 1966 to 2016). CASE PRESENTATION: Herein, we report a case of
      intestinal KS in a 21-year-old HIV-negative Ethiopian male with a long-standing
      history of steroid therapy for his underlying IgA nephropathy. Recent
      gastrointestinal biopsies confirmed an additional diagnosis of CD. Despite the
      addition of Infliximab to his therapy, his CD remained refractory, and a
      laparoscopic-assisted ileocolectomy was performed to alleviate a partial small
      bowel obstruction. Examination of his terminal ileum demonstrated a polypoid mass
      with adjacent incidental ileal submucosal nodules. These nodules were composed of
      plump spindle cells with scattered mitoses and vascular channels with
      extravasated red blood cells. Intratumoral hyaline globules were also noted.
      Immunohistochemistry revealed HHV-8 positivity, confirming the histologic
      impression of KS. CONCLUSIONS: Here we report the fourth case of KS in CD in an
      HIV-negative patient and only the third case of isolated intestinal KS in the
      setting of CD. A review of the literature suggests that attenuation of
      immunosuppressive therapy may be adequate management of iatrogenic KS in the
      absence of a systemic HHV-8 infection.

PMID- 29169277
TI  - Reconstructing protein and gene phylogenies using reconciliation and soft
      clustering.
AB  - The architecture of eukaryotic coding genes allows the production of several
      different protein isoforms by genes. Current gene phylogeny reconstruction
      methods make use of a single protein product per gene, ignoring information on
      alternative protein isoforms. These methods often lead to inaccurate gene tree
      reconstructions that require to be corrected before phylogenetic analyses. Here,
      we propose a new approach for the reconstruction of gene trees and protein trees
      accounting for alternative protein isoforms. We extend the concept of
      reconciliation to protein trees, and we define a new reconciliation problem
      called MinDRGT that consists in finding a gene tree that minimizes a double
      reconciliation cost with a given protein tree and a given species tree. We define
      a second problem called MinDRPGT that consists in finding a protein supertree and
      a gene tree minimizing a double reconciliation cost, given a species tree and a
      set of protein subtrees. We propose a shift from the traditional view of protein
      ortholog groups as hard-clusters to soft-clusters and we study the MinDRPGT
      problem under this assumption. We provide algorithmic exact and heuristic
      solutions for versions of the problems, and we present the results of
      applications on protein and gene trees from the Ensembl database. The
      implementations of the methods are available at https://github.com/UdeS
      CoBIUS/Protein2GeneTree and https://github.com/UdeS-CoBIUS/SuperProteinTree .

PMID- 29169278
TI  - Caspase-independent cell death: An anti-cancer double whammy.

PMID- 29169279
TI  - Evaluation of Intravenous Vancomycin Pharmacokinetic Parameters in Patients With
      Acute Brain Injury.
AB  - BACKGROUND: Vancomycin is a glycopeptide antibiotic that is primarily cleared by
      renal elimination. Patients with acute brain injury often exhibit augmented renal
      clearance which has been associated with subtherapeutic vancomycin
      concentrations. OBJECTIVE: To determine whether population pharmacokinetics
      accurately predict vancomycin empiric dose frequency in patients with acute brain
      injury. METHODS: This was a single-center, retrospective cohort study conducted
      following institutional review board approval at Virginia Commonwealth University
      Health System. Data were collected from patients 18 years of age or older
      admitted with acute brain injury. The primary outcome was the difference in the
      elimination rate constant of vancomycin between population predicted
      pharmacokinetics and patient-specific pharmacokinetics. RESULTS: A total of 158
      patients were included in the analysis. A test of the paired differences between
      the mean population predicted and patient-specific elimination rate constants
      showed that the mean population predicted elimination rate constant was larger by
      0.0211 h-1 (95% confidence interval [CI]: -0.028 to -0.015). The difference
      between the mean population predicted and patient-specific half-lives showed that
      the mean population predicted half-life was shorter by 1.01 hours (95% CI: 0.7
      1.3). Vancomycin was administered at a mean initial dose of 15.4 mg/kg (standard
      deviation [SD] = 2.2), with an average frequency of 12 hours (SD = 1.1). The
      average trough concentration at steady state was 9.9 ug/mL (SD = 4.9).
      CONCLUSIONS: The small clinical difference in population and patient-specific
      elimination rate constants demonstrates that population pharmacokinetics may be
      an accurate empiric dosing strategy for determining vancomycin dose frequency in
      patients with acute brain injury.

PMID- 29169280
TI  - Apoptosis signal-regulating kinase 1 in regulated necrosis.

PMID- 29169281
TI  - Pitfalls of Frozen Section Diagnosis for Paraganglioma: A Clinicopathologic
      Analysis and Review of the Literature.
AB  - Few paraganglioma (PG) cases include frozen section diagnoses, and therefore, the
      accuracy of frozen section diagnosis for PG remains unknown. To better understand
      the histologic characteristics and pitfalls of frozen section findings for PG, 15
      PG cases with frozen section diagnoses were selected from 12 articles through
      PubMed (1984-2015). In addition, we included 3 cases of PG for which
      intraoperative consultations were requested during a 5-year period (2012-2016) in
      2 hospitals. Seven PGs were from the thyroid; 2 from the pancreas; 4 from the
      mediastinum, retroperitoneum, or mesentery; 1 from the middle ear; and 4 from the
      urinary bladder (UB). Out of 18 PGs, correct diagnoses were rendered in only 2
      cases, and no thyroid or UB PGs were correctly diagnosed on intraoperative
      consultation. Thyroid PGs were frequently misdiagnosed as medullary thyroid
      carcinomas (4/7, 57%) and UB PGs were frequently misdiagnosed as malignancies.

PMID- 29169282
TI  - Efficacy of buparlisib in treating breast cancer.
AB  - INTRODUCTION: Breast cancer is the most frequent cancer in women. Despite a
      decline in breast cancer mortality, prognosis of advanced breast cancer remains
      poor. In a desperate need to improve breast cancer outcomes, newer agents that
      target molecular pathways are being tested. Deregulation of the phosphoinositide
      3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) is frequently found in
      breast cancer. This can lead to resistance of endocrine therapy and anti-HER2
      therapies. Targeting this pathway may restore sensitivity to these compounds.
      Buparlisib (BKM-120) is an orally active pan-PI3K inhibitor evaluated in
      different tumor types. Areas covered: Buparlisib is one of the most investigated
      PI3K inhibitors. Preclinical and clinical studies of buparlisib in breast cancer
      are analyzed and discussed. This article reviews the status of buparlisib,
      completed and ongoing trials, and its safety. Expert opinion: PI3K inhibitors
      show promising results in breast cancer. However, we raise a number of issues
      including the identification of biomarkers to predict treatment response and
      strategies to counteract resistance. Moreover, its toxicity profile could limit
      its extensive use.

PMID- 29169283
TI  - Time-lapse microscopic observation of non-dividing cells in cultured human
      osteosarcoma MG-63 cell line.
AB  - Cancer stem cells resemble normal tissue-specific stem cells in many aspects,
      such as self-renewal and plasticity. Like their non-malignant counterparts,
      cancer stem cells are suggested to exhibit a relative quiescence. The established
      cancer cell lines reportedly harbor slow-proliferating cells that are positive
      for some cancer stem cells markers. However, the fate of these cells and their
      progeny remains unknown. We used time-lapse microscopy and the contrast-based
      segmentation algorithm to identify and monitor actively dividing and non-dividing
      cells in human osteosarcoma MG-63 cell line. Within the monitored field of view
      the non-dividing cells were represented by three cells that never divided, and
      one cell that attempted to divide, but failed cytokinesis, and later, after
      significantly prolonged division, produced the progeny with enlarged segmented
      nuclei, thus pointing to a possible mitotic catastrophe. Together, these cells
      initially constituted about 6.2% of the total number of seeded cells, yet only
      0.02% of all cells at the end of the observation period when cells became
      confluent. Non-dividing cells were characterized by rounded shape, dark nuclei,
      random cytoplasmic streaming and subtle oscillatory movement, however, they did
      not migrate and rarely formed cell-cell contacts as compared to actively dividing
      cells. Our data indicate that the observed non-dividing MG-63 cells do not have a
      growth advantage over other cells and, therefore, they do not contribute to the
      cancer stem cells pool.

PMID- 29169285
TI  - Relaxant effect of Curcuma longa on rat tracheal smooth muscle and its possible
      mechanisms.
AB  - CONTEXT: Turmeric is a spice obtained from the root of Curcuma longa L.
      (Zingiberaceae) with anti-aging, anticancer, anti-Alzheimer's disease,
      antioxidant and other medicinal properties. OBJECTIVE: The relaxant effect of C.
      longa on rat tracheal smooth muscle and its possible mechanisms were investigated
      in this study. MATERIALS AND METHODS: The relaxant effects of four cumulative
      concentrations of hydro-ethanol extract of C. longa (6.25, 12.5, 25, 50 mg/mL)
      were studied on tracheal smooth muscle precontracted by methacholine or KCl in
      non-incubated or incubated with different substances including propranolol,
      diltiazem, L-NAME, glibenclamide, atropine, chlorpheniramine, indomethacin and
      papaverine. The duration of the study was 84 days. RESULTS: In non-incubated
      tracheal smooth muscle, the extract of C. longa showed significant concentration
      dependent relaxant effects (p < 0.001 for all concentrations on both KCl and
      methacholine-induced contraction). There was no significant difference in the
      relaxant effects between C. longa and theophylline in both methacholine and KCl
      induced contraction conditions. In tissues incubated with propranolol, diltiazem,
      L-NAME and glibenclamide on methacholine-induced contraction and in tissues
      incubated with atropine, chlorpheniramine, indomethacin and papaverine on KCl
      induced contraction, the extract also showed significant concentration-dependent
      relaxant effects (p < 0.001). EC50 values of C. longa between non-incubated
      (16.22 +/- 0.62) and incubated tissues (atropine: 13.03 +/- 0.55,
      chlorpheniramine: 12.94 +/- 0.68, indomethacin: 14.80 +/- 0.57 and papaverine:
      16.16 +/- 1.42) were not significantly different. CONCLUSIONS: Tracheal smooth
      muscle relaxant effects of C. longa, were comparable to those of theophylline,
      which could be due to the presence of methylxanthines or its possible interaction
      with non-adrenergic non-cholinergic nervous system.

PMID- 29169286
TI  - Sclerosing Mucoepidermoid Carcinoma in the Parotid Gland With CRTC1-MAML2 Fusion:
      A Case Report.
AB  - In this article, we report a case of sclerosing mucoepidermoid carcinoma (MEC)
      arising in the parotid gland, with CRTC1-MAML2 gene fusion. A 73-year-old woman
      with a mass in the right parotid region was referred to our hospital.
      Radiological imaging tests revealed a well-defined mass, measuring 25 mm in
      diameter, with foci of calcification in the deep lobe of the parotid gland,
      extending to the parapharyngeal space. Microscopically, the tumor was composed of
      a proliferation of atypical glandular epithelial cells having intracytoplasmic
      mucin, squamoid cells, and intermediate cells arranged in nests embedded in a
      fibrosclerotic stroma, associated with a dense chronic inflammatory infiltrate
      containing immunoglobulin G4-immunoreactive plasma cells. Reverse transcription
      polymerase chain reaction analysis using a formalin-fixed, paraffin-embedded
      tumor tissue specimen revealed the CRTC1-MAML2 fusion gene transcript. This is
      the first report of sclerosing MEC with the detection of the MEC-associated
      fusion gene, reinforcing a common genetic association between MEC and sclerosing
      MEC.

PMID- 29169284
TI  - VEGFC/VEGFR3 Signaling Regulates Mouse Spermatogonial Cell Proliferation via the
      Activation of AKT/MAPK and Cyclin D1 Pathway and Mediates the Apoptosis by
      affecting Caspase 3/9 and Bcl-2.
AB  - We have previously shown that the transcript levels of Vegfc and its receptor
      Vegfr3 were high in spermatogonia and extremely low in spermatocytes and
      spermatids. However, it remains unknown about the functions and the mechanisms of
      VEGFC/VEGFR3 signaling in regulating the fate determinations of spermatogonia. To
      this end, here we explored the role and signaling pathways of VEGFC/VEGFR3 by
      using a cell line derived from immortalized mouse spermatogonia retaining markers
      of mitotic germ cells, namely GC-1 cells. VEGFR3 was expressed in mouse primary
      spermatogonia and GC-1 cells. VEGFC stimulated the proliferation and DNA
      synthesis of GC-1 cells and enhanced the phosphorylation of PI3K-AKT and MAPK,
      whereas LY294002 (an inhibitor for AKT) and CI-1040 (an inhibitor for MAPK)
      blocked the effect of VEGFC on GC-1 cell proliferation. Furthermore, VEGFC
      increased the transcripts of c-fos and Egr1 and protein levels of cyclin D1, PCNA
      and Bcl-2. Conversely, the blocking of VEGFC/VEGFR3 signaling by VEGFR3 knockdown
      reduced the phosphorylation of AKT/MAPK and decreased the levels of cyclin D1 and
      PCNA. Additionally, VEGFR3 knockdown not only resulted in more apoptosis of GC-1
      cells but also led to a decrease of Bcl-2 and promoted the cleavage of Caspase
      3/9 and PARP. Collectively, these data suggested that VEGFC/VEGFR3 signaling
      promotes the proliferation of GC-1 cells via the AKT /MAPK and cyclin D1 pathway
      and it inhibits the cell apoptosis through Caspase-3/9, PARP and Bcl-2. Thus,
      this study sheds a novel insight to the molecular mechanisms underlying the fate
      decisions of mammalian spermatogonia.

PMID- 29169287
TI  - Point-of-care testing (POCT) and evidence-based laboratory medicine (EBLM) - does
      it leverage any advantage in clinical decision making?
AB  - Point-of-care testing (POCT) is the analysis of patient specimens outside the
      clinical laboratory, near or at the site of patient care, usually performed by
      clinical staff without laboratory training, although it also encompasses patient
      self-monitoring. It is able to provide a rapid result near the patient and which
      can be acted upon immediately. The key driver is the concept that clinical
      decision making may be delayed when samples are sent to the clinical laboratory.
      Balanced against this are considerations of increased costs for purchase and
      maintenance of equipment, staff training, connectivity to the laboratory
      information system (LIS), quality control (QC) and external quality assurance
      (EQA) procedures, all required for accreditation under ISO 22870. The
      justification for POCT depends upon being able to demonstrate that a more timely
      result (shorter turnaround times (TATs)) is able to leverage a clinically
      important advantage in decision making compared with the central laboratory (CL).
      In the four decades since POCT was adapted for the self-monitoring of blood
      glucose levels by subjects with diabetes, numerous new POCT methodologies have
      become available, enabling the clinician to receive results and initiate
      treatment more rapidly. However, these instruments are often operated by staff
      not trained in laboratory medicine and hence are prone to errors in the
      analytical phase (as opposed to laboratory testing where the analytical phase has
      the least errors). In some environments, particularly remote rural settings, the
      CL may be at a considerable distance and timely availability of cardiac troponins
      and other analytes can triage referrals to the main centers, thus avoiding
      expensive unnecessary patient transportation costs. However, in the Emergency
      Department, availability of more rapid results with POCT does not always
      translate into shorter stays due to other barriers to implementation of care. In
      this review, we apply the principles of evidence-based laboratory medicine (EBLM)
      looking for high quality systematic reviews and meta-analyses, ideally
      underpinned by randomized controlled trials (RCTs), looking for evidence of
      whether POCT confers any advantage in clinical decision making in different
      scenarios.

PMID- 29169288
TI  - Human studies with microneedles for evaluation of their efficacy and safety.
AB  - INTRODUCTION: During the past two decades, many studies have documented the
      development of microneedles (MNs) as a feasible technique for the effective
      administration of drugs. More and more human studies have been done with MNs to
      bridge the gap between research and market applications that provide efficacious
      techniques for clinical implementation. Areas covered: The aim of this review is
      provide a brief description of the status of human study with MNs and to
      demonstrate progress for the right use of microneedle arrays in clinical
      settings. It also describes the considerations for clinical application with each
      type of MNs. Expert opinion: Microneedle systems were introduced to overcome the
      limitations of conventional methods of drug administration. Lots of microneedle
      systems have undergone clinical evaluation to determine their efficacy and
      safety, and many studies have demonstrated positive results. The successful
      clinical use of the microneedle in vaccine therapy is remarkable and supports the
      importance of conducting further tests in a wide range of medical applications.
      Self-administered MNs appeared to be an attractive alternative method that needs
      further research to become a reality in the near future.

PMID- 29169289
TI  - School Nurses' Experiences Working With Students With Mental Health Problems: A
      Qualitative Study.
AB  - The aim was to describe school nurses' experiences working with students with
      mental health problems. In this inductive qualitative study, interviews were
      conducted with 14 school nurses in Sweden. The content analysis revealed three
      themes: (1) sense of worriedness about working with students with mental health
      problems, (2) taking care of students with mental health issues was an
      opportunity for personal and professional development, and (3) the experience of
      making a difference for young people with mental health problems. The school
      nurses working with students who have mental health problems had to cope with
      their own emotions, worries, and feelings of insufficiency. However, the school
      nurses also found the work to be meaningful and rewarding because they
      appreciated the opportunity for personal and professional development while
      taking care of students with mental health problems. They felt grateful for
      having a profession that had a huge impact on children's/adolescents' lives.

PMID- 29169291
TI  - Understandings of participation in daily activity services among people with
      intellectual disabilities: A pedagogical sociocultural perspective.
AB  - This study sought to explore different understandings of participation in daily
      activity services among people with intellectual disabilities. Using a
      pedagogical sociocultural perspective, the research focused on individuals'
      perspectives and understandings as well as their account of social interaction,
      working and learning. In all, 17 people working in daily activity services were
      interviewed once, and, of these, 14 were interviewed a second time. Using
      qualitative content analysis, two themes and three categories were singled out.
      The results show that participation can be understood in two major ways: social
      interaction and performing work tasks.

PMID- 29169290
TI  - Interpolated mapping and investigation of environmental radioactivity levels in
      soils and mushrooms in the Middle Black Sea Region of Turkey.
AB  - The activity concentration of natural (238U, 232Th, and 40K) and artificial
      (137Cs) radionuclides was determined in 50 samples (obtained from the same
      station) from various species of mushrooms and soil collected from the Middle
      Black Sea Region (Turkey). The activities of 238U, 232Th, 40K, and 137Cs were
      found as 84 +/- 16, 45 +/- 14, 570 +/- 28, and 64 +/- 6 Bq kg-1 (dry weight),
      respectively, in the mushroom samples and as 51 +/- 6, 41 +/- 6, 201 +/- 11, and
      44 +/- 4 Bq kg-1, respectively, in the soil samples for the entire area of study.
      The results of all radionuclide activity measurements, except those of 238U and
      232Th in the mushroom samples, are consistent with previous studies. In the soil
      samples, the mean values of 238U and 232Th are above the world mean, and the
      activity mean of 40K is below the world mean. Finally, the activity estimation
      was made with both the soil and mushroom samples for unmeasured points within the
      study area by using the ordinary kriging method. Radiological distribution maps
      were generated.

PMID- 29169292
TI  - Use of a translucent refuge for Xenopus tropicalis with the aim of improving
      welfare.
AB  - Xenopus tropicalis is an increasingly important animal model in a variety of
      biological research fields. In many countries legislation exists to promote and
      increase welfare wherever possible, including the ability to view animals during
      daily husbandry with minimal stress to the animal. X. tropicalis ( n = 16) refuge
      use was investigated; it was found that the animals significantly preferred black
      opaque overhead cover to open-ended pipes or closed-off ceramic plants pots in
      refuge choice experiments. This experiment was repeated by replacing the opaque
      black overhead cover with red filters. A significant preference for overhead
      cover was seen for the red translucent cover compared with other available
      refuges, suggesting that X. tropicalis may adopt translucent refuges due to their
      visual inabilities. The inability of frogs to see certain wavelengths of light
      may allow staff to view them whilst simultaneously providing the refuge of
      choice.

PMID- 29169293
TI  - Qualitative Analysis of Faith Community Nurse-Led Cognitive-Behavioral and
      Spiritual Counseling for Dementia Caregivers.
AB  - This article presents themes emerging from semistructured interviews with
      dementia family caregivers in rural communities who participated in an
      integrative, cognitive-behavioral and spiritual counseling intervention, and with
      faith community nurses (FCNs) who delivered the intervention. The primary
      objectives of the counseling intervention were to ameliorate dementia caregivers'
      depressive affect and the severity of their self-identified caregiving and self
      care problems. The qualitative portion of the study was intended to elicit
      caregivers' and FCNs' perceptions of the benefits and drawbacks of the
      intervention. We conducted interviews with seven FCN/caregiver pairs 4 times
      during the 6-month counseling process, totaling 56 interviews. Themes emerging
      from the interviews included caregivers' perception of burden and care partners'
      problem behavior; formation of therapeutic alliance between FCNs and caregivers;
      problem-solving skills, tools, and resources; caregivers' use of problem-solving
      strategies; spirituality in caregiving and counseling processes; FCNs' prior
      professional experience; and caregiver and FCN time constraints.

PMID- 29169294
TI  - Susceptibility of functional impairment scales to noncredible responses in the
      clinical evaluation of adult ADHD.
AB  - OBJECTIVE: A growing body of research questions the reliance of symptom self
      reports in the clinical evaluation of attention-deficit/hyperactivity disorder
      (ADHD) in adulthood. A recent study suggested that also impairment reports are
      vulnerable to noncredible responses, as derived from a simulation design using a
      global functional impairment scale. The present study aims to add evidence to
      this issue, by using an ADHD specific impairment scale in a simulation design on
      large samples. METHOD: Impairment ratings on the Weiss Functional Impairment
      Rating Scale (WFIRS) of 62 patients with ADHD were compared to 142 healthy
      individuals who were instructed to show normal behavior. Furthermore, impairment
      ratings of patients with ADHD were compared to ratings of 330 healthy individuals
      who were randomly assigned to one of four simulation conditions that were
      instructed to complete the scale as if they had ADHD. RESULTS: Patients with ADHD
      reported higher levels of impairment than the healthy control group in all
      domains of life. Furthermore, individuals instructed to feign ADHD indicated
      higher levels of impairments in most domains of life compared to control
      participants and genuine patients with ADHD. The group differences between
      individuals feigning ADHD and individuals with genuine ADHD, however, were only
      small to moderate. Further analyses revealed that the WFRIS was not useful to
      successfully differentiate genuine from feigned ADHD. CONCLUSIONS: The present
      study confirms the conclusion that self-reported impairments are susceptible to
      noncredible responses and should be used with caution in the clinical evaluation
      of adult ADHD.

PMID- 29169295
TI  - Observed and expected mortality in the German skin cancer screening pilot project
      SCREEN.
AB  - Objective The main purpose of skin cancer screening is melanoma mortality
      reduction. Before the implementation of nationwide German skin cancer screening,
      the pilot project SCREEN was conducted in Schleswig-Holstein in 2003-2004. We
      aimed to determine whether the pilot project had achieved a mortality reduction.
      Methods Using an incidence-based approach (patients with both melanoma diagnosis
      and death in 2003-2008), we compared the observed melanoma mortality of the
      SCREEN cohort to the melanoma mortality expected without screening in the general
      population of Saarland. Results The age- and sex-standardized melanoma mortality
      ratio (SMR) for 5.5 years of follow-up was 0.59 (95% confidence interval, 0.40
      0.83). Conclusion Our results indicate reduced mortality in the SCREEN cohort.
      Several potential biases cannot be excluded, but most of them tend to inflate the
      SMR.

PMID- 29169296
TI  - Blackfullas in ivory towers: referenced reflections of a Bundjalung graduate
      nurse.
AB  - BACKGROUND: Indigenous representation is essential to ensure the health workforce
      is culturally capable and safe for Indigenous patients. However, Indigenous
      Peoples remain underrepresented in tertiary education and the health workforce.
      AIM: This aim of this paper is to offer an unmediated, Aboriginal nurses'
      perspective, on the experience, barriers and challenges of undertaking a Bachelor
      of Nursing degree. DESIGN: Referenced reflection. RESULTS: Education providers
      must be culturally capable themselves before teaching Indigenous content and
      facilitating sensitive classroom discussions. Financial, social and educational
      support is crucial to equip Indigenous students for tertiary study. CONCLUSION:
      To retain Indigenous students and contribute to a culturally capable workforce,
      it is imperative to listen and respond to Indigenous Peoples voices to shape
      learning experiences and support.

PMID- 29169297
TI  - Massive upper gastrointestinal bleeding after organophosphate poisoning: a case
      report.

PMID- 29169298
TI  - Self-initiated spatial working memory in young and older adults.
AB  - The age-related decline in working memory (WM) has been studied extensively. Yet,
      research has focused mainly on one aspect of memory, in which older adults
      memorised information provided to them, neglecting the frequent everyday
      behaviour in which memory is self-initiated (SI), meaning that individuals
      memorise information they selected themselves. The present study used a modified
      spatial span task in which young and older adults memorised spatial sequences
      they constructed themselves, or random sequences provided to them. The results
      revealed that young and older adults carefully planned and constructed structured
      spatial sequences, by minimising distances between successive locations, and by
      selecting sequences with fewer path crossings and with more linear shapes. Older
      adults constructed sequences that were even more structured in some aspects.
      Young and older adults benefited from self-initiation to the same extent, showing
      similar age-related declines in SI and provided spatial WM. Overall, the study
      shows that older adults have access to metacognitive knowledge on the structure
      of efficient WM representations that benefit accuracy, and shows that older
      adults can use strategic encoding processes efficiently when encoding is SI. More
      generally, SI WM explores an important aspect of behaviour, demonstrating how
      older adults shape their environment to facilitate cognitive functioning.

PMID- 29169299
TI  - The changing case-mix of hip fractures in Scotland - evidence from the Scottish
      Hip Fracture Audit.
AB  - Until discontinued in 2008, the Scottish Hip Fracture Audit collected and
      reported on data relating to the quality of care of hip fracture patients in
      Scotland. In 2013, the audit was recommenced under the umbrella of the MSK Audit
      group, which audits high volume orthopaedic pathways across Scotland. Our aim is
      to report on the changes in the demographics of hip fracture patients in Scotland
      between 2003 and 2013. There was an increase in the proportion of male patients
      from 2003 to 2013 (22.4% to 29.5%; p < 0.0001). An increased percentage of hip
      fracture patients were admitted from their own home (63.9% to 73.1%; p < 0.0001).
      Both these factors have deleterious effects on the outcome, and use of necessary
      resources, following hip fracture. There was also an increase in the percentage
      of patients who were American Society of Anesthesiologists Grade 3 (52.9% to
      56.4%). Over the last decade, there has been a shift in the demographics of
      Scotland's hip fracture patients. If hip fracture incidence increases as
      predicted, this potentially more-challenging case-mix will likely impact on
      multiple health resources.

PMID- 29169300
TI  - Arterio-biliary fistulas: What to choose as endovascular treatment?
AB  - Objectives Endovascular procedures are the treatment of choice in cases of
      intrahepatic fistulas. Arterio-biliary fistulas are the rarest and most difficult
      to treat, due to high risk of infection. Methods Eight cases of persistent
      hemobilia that developed as a result of arterio-biliary fistulas are presented.
      Five cases developed as a result of iatrogenic injury, two cases as a result of
      chronic infection, one case as a consequence of trauma. Results Patients were
      treated using endovascular embolization or combined endovascular and endoscopic
      biliary tract revision. The results were monitored after six to seven days and
      one month after embolization. The embolizations were considered effective in all
      cases. One patient had four asynchronous fistulas requiring separate treatments
      sessions. Four patients required a revision of their biliary ducts after
      embolization and restoration of patency. In one patient, a migration of the coil
      to biliary ducts occurred. Conclusion Endovascular treatment of arterio-biliary
      fistulas is safe and effective. The use of embolization with soft and
      biodegradable materials like histoacrylic glue or thrombin may be the optimal
      method of treatment in comparison with coils which have a risk of migration or
      chronic infection.

PMID- 29169301
TI  - Utilization of stent grafts in the management of arteriovenous access
      pseudoaneurysms.
AB  - Objective Endovascular stent graft repair for exclusion of pseudoaneurysm is
      currently being explored to replace open surgical repair as current management.
      The objective of the study was to evaluate the clinical safety and efficacy of
      endovascular stent graft intervention in pseudoaneurysms complicating
      arteriovenous reconstructions in patients on chronic hemodialysis. Methods A
      retrospective analysis of all pseudoaneurysms treated with stent grafts at our
      institution over a period of five years was performed. The indications for
      endovascular intervention included bleeding from the pseudoaneurysm, infection,
      and significant skin compromise overlying the pseudoaneurysm or combination of
      the above. The rates of technical success, complication, and primary patency were
      measured at one-week, one-month, and six-month follow-up. Results A total of 33
      endovascular stent graft interventions in 29 patients were performed for the
      treatment of pseudoaneurysms. The average age of patients was 68 years (range 31
      90 years), with 13 female. Diabetes and hypertension were present in 15 and 22
      patients, respectively. In eight patients, there was evidence of active infection
      at the fistula site. The choice of stent grafts include Viabahn ( n = 31),
      Wallgraft ( n = 1), and i-Cast ( n = 1). The initial technical success rate was
      94%. The two failed interventions included occlusion of inflow artery with
      immediate conversion to open procedure ( n = 1) and incomplete pseudoaneurysm
      exclusion ( n = 1). Primary patency at one month and six months was 83 and 60%,
      respectively. An additional balloon angioplasty of outflow tract or central
      stenosis was performed in 18 cases (54%). The explanation of stent grafts due to
      persistent or recurrent bacteremia/site infection was required in four out of
      eight patients. The average time to explanation was 93 days (range 6-204 days).
      Conclusion The stent graft implantation is a safe, minimally invasive and
      efficient way to control and manage arteriovenous accesses with pseudoaneurysms.
      In the presence of infection, this approach may be less durable.

PMID- 29169303
TI  - Inclusion and exclusion strategies for conducting meta-analyses.
AB  - Some of the most important decisions that a researcher will make when conducting
      a meta-analysis are decisions about the search strategies and inclusion/exclusion
      criteria. Decisions regarding inclusion/exclusion criteria serve to define the
      scope of a meta-analysis and search strategy decisions can have a large impact on
      how well the results of a meta-analysis actually represent the existing body of
      literature. In this article, we provide descriptions and recommendations for
      performing searches and making inclusion/exclusion decisions. We also provide a
      review of 65 meta-analyses of psychotherapy versus pharmacotherapy in order to
      offer frequency data on the use of various search strategies and
      inclusion/exclusion decisions in the field.

PMID- 29169302
TI  - Laughter therapy as an intervention to promote psychological well-being of
      volunteer community care workers working with HIV-affected families.
AB  - The study explores the experiences of volunteer community care workers working
      with HIV-affected families, participating in laughter therapy. Laughter therapy
      is being used as an intervention to positively influence individuals experiencing
      various forms of emotional distress. Community care workers play a vital role in
      the support of the HIV/AIDS-infected and -affected members in communities. The
      nature of this type of work and their limited training contributes to high levels
      of secondary trauma and emotional exhaustion. The purpose of the study was
      firstly, to explore the effects of working with orphans and vulnerable children
      (OVC) on the community care workers and secondly, to establish the impact that
      laughter therapy has to positively combat stresses of working within the care
      workers' environment. All the community care workers from a community-based
      organisation that provides care for HIV/AIDS-infected and -affected OVC and their
      families in the greater region of Soweto, South Africa, took part in daily
      laughter therapy sessions for one month. To assess the experiences of
      participants of laughter therapy, seven community care workers agreed to
      participate in a mixed method assessment. Interviews were conducted before and
      after the intervention using the Interpretative Phenomenological Analysis as
      framework. As supportive data, a stress and anxiety and depression scale were
      added in the interview. Participants reported more positive emotions, positive
      coping, improved interpersonal relationships and improvement in their care work
      after exposure to laughter therapy. Quantitative results on stress, anxiety and
      depression for each participant confirmed observed changes. Laughter therapy as a
      self-care technique has potential as a low-cost intervention strategy to reduce
      stress and counteract negative emotions among people working in highly emotional
      environments.

PMID- 29169304
TI  - Determination of the predictive clinical parameters to diagnose chronic
      exertional compartment syndrome.
AB  - Chronic exertional compartment syndrome (CECS) is characterized by pain occurring
      during physical activity. As clinical examination is not sufficient to diagnose
      it, intracompartmental pressure (ICP) measure is used for CECS confirmation.
      Numerous clinical signs are reported but their diagnosis predictive ability has
      never been studied. We aimed to determine if the 12 classically reported clinical
      signs are predictive of CECS. We performed a single-centre retrospective cohort
      study on patients referred for CECS suspicion. Patients were asked to run on a
      treadmill. When pain occurred, post-exercise ICP was performed. We diagnosed CECS
      if the ICP was >=30 mmHg and used a logistic regression to calculate the
      predictive value of clinical signs. One hundred twenty-five patients were
      evaluated. Ninety-six had CECS and 29 did not, according to the ICP 30 mmHg cut
      off. Anterior and lateral compartments were the most frequently affected. After
      exercise, mean ICP was 58.6 mmHg +/- 20.5 in the group with CECS versus 20.9 mmHg
      +/- 4 in the group without (p < .001). Muscle hardness, muscle hernia after
      exercise, absence of pain at rest and pain recidivism for the same exercise were
      predictive of CECS. The predictive model associated muscle hardness (Odds Ratio
      (OR) = 2.18; p < .001) and muscle hernia after exercise (OR = 1.44; p < .001).
      This model identified 88.6% of CECS subjects. The ROC curve area was 0.808 [95%
      CI: 0.71-0.90]. This study confirmed the importance of clinical parameters to
      diagnose CECS. A better knowledge of the relevant parameters could help
      physicians to indicate invasive examinations.

PMID- 29169305
TI  - The Vulnerability of Occupational Health and Safety to Deregulation: The
      Weakening of Information Regulations during the Economic Crisis in Korea.
AB  - This study was conducted to investigate the causes and consequences of the
      vulnerability of occupational health and safety (OHS) regulations to deregulation
      during a period of economic crisis in the Republic of Korea. Analysis of Korea's
      national regulation database revealed that the vulnerability of OHS regulations
      to deregulation was related to the fact that OHS policy included many regulations
      without direct deregulatory impacts on workers. The most affected victim of this
      characteristic was information regulation that provided a legal basis for
      government's monitoring and inspection of OHS activities. The massive relaxation
      of information regulation has the potential to weaken government oversight and to
      tempt businesses to hide industrial accidents. Since changes in regulations
      without direct deregulatory impacts are not easily identifiable by workers,
      careful monitoring of deregulation is necessary to prevent policy impacts harmful
      to workers' health and safety.

PMID- 29169306
TI  - Occupational Stress Among Home Healthcare Workers: Integrating Worker and Agency
      Level Factors.
AB  - Home healthcare work is physically and emotionally exhausting. In addition, home
      healthcare workers frequently work under precarious work arrangements for low
      wages and in poor work conditions. Little is known about how sources of job
      strain for home healthcare workers might be reduced. This research examines the
      occupational stressors among paid home care workers by analyzing home healthcare
      agency characteristics and individual home healthcare workers' experiences in
      upstate New York agencies (n = 9). The study augments existing theoretical models
      and describes new sources of stress arising from the nature of agency-based
      caregiving. Results feature the analysis of both agency executives' (n = 20) and
      home healthcare workers' narratives (n = 25) to make the agency's inner workings
      more transparent. Agency structures and culture are implicated in the lack of
      progress to address home care workers' health problems. Policy change should
      focus on compensation, healthier work conditions, and training requirements.

PMID- 29169307
TI  - Adult orthodontics in the Republic of Ireland: specialist orthodontists'
      opinions.
AB  - OBJECTIVES: To report the opinions of specialist orthodontists regarding the
      profile, characteristics and treatment of adults currently undergoing orthodontic
      treatment in the Republic of Ireland (ROI) Design/setting: A national cross
      sectional questionnaire study in the ROI. METHOD: A pilot-tested questionnaire
      was distributed to 122 specialist orthodontists in the ROI. Questions addressed
      general and treatment information for current adult orthodontic patients. Those
      whose treatment involved orthognathic surgery were not excluded. RESULTS: A
      response of 83% was obtained. Ninety-five per cent of specialists reported
      treating adults, most of whom were self-referred and were typically professional,
      female and aged 25-35 years. The overall ratio quoted of professionals to non
      professionals was almost 3:2. For 50% of specialists, males were estimated to
      account for 20-40% of their adult cases and for 23%, this increased to an
      estimated 40-60%. Class II division 1 malocclusion and skeletal II were
      considered the most common dentofacial characteristics. Occlusal features
      encountered in decreasing frequency were generalised crowding, increased overjet,
      deep overbite, late lower incisor crowding, spacing and impacted teeth. Fifteen
      per cent reported that at least 10% of their adult cases required orthodontics
      with maxillofacial surgery but 8% reported that this was at least 50%. Treatment
      challenges commonly acknowledged were overbite reduction, anchorage management,
      'black triangles' and overjet reduction. Tooth whitening was reckoned to be used
      by 19% of specialists. Aesthetic upper and stainless steel lower brackets were
      indicated to be used most often whereas only 19% used clear aligners and 10% used
      lingual appliances often. CONCLUSIONS: The profile and characteristics of adults
      currently undergoing orthodontic treatment in the ROI were diverse. Higher
      estimates were quoted for self- than for general dental practitioner-referral. A
      high percentage of treatment was reported to be undertaken for non-professionals
      and males. A wide range of treatment and varying use of appliance types were
      cited.

PMID- 29169308
TI  - Factors influencing nurse-to-parent communication in culturally sensitive
      pediatric care: a qualitative study.
AB  - BACKGROUND: To deliver quality healthcare to diverse patients, effective
      commmunication is key. Little evidence exists about what factors influence nurse
      to-parent communication in culturally sensitive pediatric care. OBJECTIVE: The
      aim of this study was to explore factors that influence nurse-to-parent
      communication in the provision of culturally sensitive pediatric care. DESIGN:
      This study employed a qualitative content analysis. METHOD: The participants
      included 25 nurses and 9 parents from pediatric wards of hospitals located in
      Northwest and Central Iran. Semi-structured interviews were conducted. Data were
      analyzed using Graneheim and Lundman's method of content analysis. RESULTS:
      Factors that influenced the nurse-to-parent communication in pediatric culturally
      sensitive care were 1-organizational factors (inefficient policies and
      professional factors) and 2-human factors (nurse-related factors and unique
      characteristics of the family). Sub-categories included: lack of definitive
      policies for delivering cultural healthcare, insufficient cultural healthcare
      education, professional status of nursing in society, time, individual
      characteristics, cultural knowledge, cultural differences, and family's health
      literacy. CONCLUSION: The Iranian healthcare system requires a paradigm shift
      regarding the provision of culturally sensitive care.

PMID- 29169309
TI  - Letter Regarding: Weightbearing vs Gravity Stress Radiographs for Stability
      Evaluation of Supination-External Rotation Fractures of the Ankle.

PMID- 29169310
TI  - Response to "Letter Regarding: Weightbearing vs Gravity Stress Radiographs for
      Stability Evaluation of Supination-External Rotation Fractures of the Ankle".

PMID- 29169312
TI  - Molecular Imaging of IGF-1R in Cancer.
AB  - The important role of insulin-like growth factor 1 receptor (IGF-1R) in malignant
      tumors has been well established. Increased IGF-1R activity promotes cancer cell
      proliferation, migration, and invasion and is associated with tumor metastasis,
      treatment resistance, poor prognosis, and shortened survival in patients with
      cancer. However, while IGF-1R has become a promising target for cancer therapy,
      IGF-1R-targeted therapy is ineffective in unselected patients. It is therefore
      essential to evaluate IGF-1R expression before treatment in order to identify
      responsive patients, monitor therapy efficacy, and estimate prognosis. Insulin
      like growth factor 1 receptor molecular imaging is an optimal method for
      assessing the expression of IGF-1R in vivo accurately and noninvasively. In this
      review, we will summarize the current status of IGF-1R molecular imaging in
      cancer, in which 5 major classes of ligands that have been developed for
      noninvasive IGF-1R molecular imaging will be discussed: natural ligands,
      monoclonal antibodies, antibody fragments, affibodies, and small molecules. For
      decades, IGF-1R molecular imaging is studied in full swing and more effort is
      needed in the future.

PMID- 29169313
TI  - Effect of Time-of-Flight and Regularized Reconstructions on Quantitative
      Measurements and Qualitative Assessments in Newly Diagnosed Prostate Cancer With
      18F-Fluorocholine Dual Time Point PET/MRI.
AB  - Recent technical advances in positron emission tomography/magnetic resonance
      imaging (PET/MRI) technology allow much improved time-of-flight (TOF) and
      regularized iterative PET reconstruction regularized iterative reconstruction
      (RIR) algorithms. We evaluated the effect of TOF and RIR on standardized uptake
      values (maximum and peak SUV [SUVmax and SUVpeak]) and their metabolic tumor
      volume dependencies and visual image quality for 18F-fluorocholine PET/MRI in
      patients with newly diagnosed prostate cancer. Fourteen patients were
      administered with 3 MBq/kg of 18F-fluorocholine and scanned dynamically for 30
      minutes. Positron emission tomography images were divided to early and late time
      points (1-6 minutes summed and 7-30 minutes summed). The values of the different
      SUVs were documented for dominant PET-avid lesions, and metabolic tumor volume
      was estimated using a 50% isocontour and SUV threshold of 2.5. Image quality was
      assessed via visual acuity scoring (VAS). We found that incorporation of TOF or
      RIR increased lesion SUVs. The lesion to background ratio was not improved by TOF
      reconstruction, while RIR improved the lesion to background ratio significantly (
      P < .05). The values of the different VAS were all significantly higher ( P <
      .05) for RIR images over TOF, RIR over non-TOF, and TOF over non-TOF. In
      conclusion, our data indicate that TOF or RIR should be incorporated into current
      protocols when available.

PMID- 29169314
TI  - Word Recognition and Learning: Effects of Hearing Loss and Amplification Feature.
AB  - Two amplification features were examined using auditory tasks that varied in
      stimulus familiarity. It was expected that the benefits of certain amplification
      features would increase as the familiarity with the stimuli decreased. A total of
      20 children and 15 adults with normal hearing as well as 21 children and 17
      adults with mild to severe hearing loss participated. Three models of ear-level
      devices were selected based on the quality of the high-frequency amplification or
      the digital noise reduction (DNR) they provided. The devices were fitted to each
      participant and used during testing only. Participants completed three tasks: (a)
      word recognition, (b) repetition and lexical decision of real and nonsense words,
      and (c) novel word learning. Performance improved significantly with
      amplification for both the children and the adults with hearing loss. Performance
      improved further with wideband amplification for the children more than for the
      adults. In steady-state noise and multitalker babble, performance decreased for
      both groups with little to no benefit from amplification or from the use of DNR.
      When compared with the listeners with normal hearing, significantly poorer
      performance was observed for both the children and adults with hearing loss on
      all tasks with few exceptions. Finally, analysis of across-task performance
      confirmed the hypothesis that benefit increased as the familiarity of the stimuli
      decreased for wideband amplification but not for DNR. However, users who prefer
      DNR for listening comfort are not likely to jeopardize their ability to detect
      and learn new information when using this feature.

PMID- 29169315
TI  - Effectiveness of Two-Talker Maskers That Differ in Talker Congruity and
      Perceptual Similarity to the Target Speech.
AB  - Previous work has shown that masked-sentence recognition is particularly poor
      when the masker is composed of two competing talkers, a finding that is
      attributed to informational masking. Informational masking tends to be largest
      when the target and masker talkers are perceptually similar. Reductions in
      masking have been observed for a wide range of target and masker differences,
      including language: Performance is better when the target and masker talkers
      speak in different languages, compared with the same language. The present study
      evaluated normal-hearing adults' sentence recognition in a two-talker masker as a
      function of the perceptual similarity between the target and each of the two
      masker streams. The target was English, and the maskers were composed of English,
      time-reversed English, or Dutch. These three masker types are known to vary in
      the informational masking they exert. The two talkers within the two-talker
      maskers were either congruent (e.g., both English) or incongruent (e.g., one
      English, one Dutch). As predicted, mean performance was worse for the congruent
      English masker than the congruent time-reversed English or congruent Dutch
      maskers. Incongruent two-talker maskers, with just one English masker stream,
      were only modestly less effective than the congruent English masker. This result
      indicates that two-talker masker effectiveness was determined predominantly by
      the one masker stream that was most perceptually similar to the target. Speech
      recognition in a single-talker masker differed only marginally between the
      English, Dutch, and time-reversed English masker types, suggesting that
      perceptual similarity may be more critical in a two-talker than a one-talker
      masker.

PMID- 29169316
TI  - Coevolution of Siglec-11 and Siglec-16 via gene conversion in primates.
AB  - BACKGROUND: Siglecs-11 and -16 are members of the sialic acid recognizing Ig-like
      lectin family, and expressed in same cells. Siglec-11 functions as an inhibitory
      receptor, whereas Siglec-16 exhibits activating properties. In humans, SIGLEC11
      and SIGLEC16 gene sequences are extremely similar in the region encoding the
      extracellular domain due to gene conversions. Human SIGLEC11 was converted by the
      nonfunctional SIGLEC16P allele, and the converted SIGLEC11 allele became fixed in
      humans, possibly because it provides novel neuroprotective functions in brain
      microglia. However, the detailed evolutionary history of SIGLEC11 and SIGLEC16 in
      other primates remains unclear. RESULTS: We analyzed SIGLEC11 and SIGLEC16 gene
      sequences of multiple primate species, and examined glycan binding profiles of
      these Siglecs. The phylogenetic tree demonstrated that gene conversions between
      SIGLEC11 and SIGLEC16 occurred in the region including the exon encoding the
      sialic acid binding domain in every primate examined. Functional assays showed
      that glycan binding preference is similar between Siglec-11 and Siglec-16 in all
      analyzed hominid species. Taken together with the fact that Siglec-11 and Siglec
      16 are expressed in the same cells, Siglec-11 and Siglec-16 are regarded as
      paired receptors that have maintained similar ligand binding preferences via gene
      conversions. Relaxed functional constraints were detected on the SIGLEC11 and
      SIGLEC16 exons that underwent gene conversions, possibly contributing to the
      evolutionary acceptance of repeated gene conversions. The frequency of
      nonfunctional SIGLEC16P alleles is much higher than that of SIGLEC16 alleles in
      every human population. CONCLUSIONS: Our findings indicate that Siglec-11 and
      Siglec-16 have been maintained as paired receptors by repeated gene conversions
      under relaxed functional constraints in the primate lineage. The high prevalence
      of the nonfunctional SIGLEC16P allele and the fixation of the converted SIGLEC11
      imply that the loss of Siglec-16 and the gain of Siglec-11 in microglia might
      have been favored during the evolution of human lineage.

PMID- 29169317
TI  - HashClone: a new tool to quantify the minimal residual disease in B-cell lymphoma
      from deep sequencing data.
AB  - BACKGROUND: Mantle Cell Lymphoma (MCL) is a B cell aggressive neoplasia
      accounting for about the 6% of all lymphomas. The most common molecular marker of
      clonality in MCL, as in other B lymphoproliferative disorders, is the
      ImmunoGlobulin Heavy chain (IGH) rearrangement, occurring in B-lymphocytes. The
      patient-specific IGH rearrangement is extensively used to monitor the Minimal
      Residual Disease (MRD) after treatment through the standardized Allele-Specific
      Oligonucleotides Quantitative Polymerase Chain Reaction based technique.
      Recently, several studies have suggested that the IGH monitoring through deep
      sequencing techniques can produce not only comparable results to Polymerase Chain
      Reaction-based methods, but also might overcome the classical technique in terms
      of feasibility and sensitivity. However, no standard bioinformatics tool is
      available at the moment for data analysis in this context. RESULTS: In this paper
      we present HashClone, an easy-to-use and reliable bioinformatics tool that
      provides B-cells clonality assessment and MRD monitoring over time analyzing data
      from Next-Generation Sequencing (NGS) technique. The HashClone strategy-based is
      composed of three steps: the first and second steps implement an alignment-free
      prediction method that identifies a set of putative clones belonging to the
      repertoire of the patient under study. In the third step the IGH variable region,
      diversity region, and joining region identification is obtained by the alignment
      of rearrangements with respect to the international ImMunoGenetics information
      system database. Moreover, a provided graphical user interface for HashClone
      execution and clonality visualization over time facilitate the tool use and the
      results interpretation. The HashClone performance was tested on the NGS data
      derived from MCL patients to assess the major B-cell clone in the diagnostic
      samples and to monitor the MRD in the real and artificial follow up samples.
      CONCLUSIONS: Our experiments show that in all the experimental settings,
      HashClone was able to correctly detect the major B-cell clones and to precisely
      follow them in several samples showing better accuracy than the state-of-art
      tool.

PMID- 29169318
TI  - Genome-wide DNA methylation profiling reveals novel epigenetic signatures in
      squamous cell lung cancer.
AB  - BACKGROUND: Epigenetic alterations are strongly associated with the development
      of cancer. The aim of this study was to identify epigenetic pattern in squamous
      cell lung cancer (LUSC) on a genome-wide scale. RESULTS: Here we performed DNA
      methylation profiling on 24 LUSC and paired non-tumor lung (NTL) tissues by
      Illumina Human Methylation 450 K BeadArrays, and identified 5214 differentially
      methylated probes. By integrating DNA methylation and mRNA expression data, 449
      aberrantly methylated genes accompanied with altered expression were identified.
      Ingenuity Pathway analysis highlighted these genes which were closely related to
      the carcinogenesis of LUSC, such as ERK family, NFKB signaling pathway, Hedgehog
      signaling pathway, providing new clues for understanding the molecular mechanisms
      of LUSC pathogenesis. To verify the results of high-throughput screening, we used
      56 paired independent tissues for clinical validation by pyrosequencing.
      Subsequently, another 343 tumor tissues from the Cancer Genome Atlas (TCGA)
      database were utilized for further validation. Then, we identified a panel of DNA
      methylation biomarkers (CLDN1, TP63, TBX5, TCF21, ADHFE1 and HNF1B) in LUSC.
      Furthermore, we performed receiver operating characteristics (ROC) analysis to
      assess the performance of biomarkers individually, suggesting that they could be
      suitable as potential diagnostic biomarkers for LUSC. Moreover, hierarchical
      clustering analysis of the DNA methylation data identified two tumor subgroups,
      one of which showed increased DNA methylation. CONCLUSIONS: Collectively, these
      results suggest that DNA methylation plays critical roles in lung tumorigenesis
      and may potentially be proposed as a diagnostic biomarker. TRIAL REGISTRATION:
      ChiCTR-RCC-12002830 Date of registration: 2012-12-17.

PMID- 29169320
TI  - Phylogeography of Nasutitermes corniger (Isoptera: Termitidae) in the Neotropical
      Region.
AB  - BACKGROUND: The Neotropical Region is known for its biodiversity and ranks third
      in number of known termite species. However, biogeographic and phylogeographic
      information of termites of this region is limited compared to other world
      geographic regions. Nasutitermes corniger is widely distributed in the region and
      is of considerable economic importance. The goal of this study was to describe
      the phylogeography of N. corniger in the Neotropical Region, to better understand
      its evolutionary processes. RESULTS: The sampled populations of N. corniger
      showed high genetic variation. Results indicated strong geographic structure
      among N. corniger populations, with most haplotypes not broadly shared among
      separated locations. Phylogeographic analyses showed a dispersal route for N.
      corniger from Central America into South America via the Isthmus of Panama, with
      subsequent dispersal through the highlands east of the Andes and into eastern
      regions of the continent. The majority of haplotypes were limited in distribution
      to proximal regions, corresponding to particular biomes (Atlantic Forest,
      Amazonia, Chaco, Cerrado and Caatinga). CONCLUSIONS: Nasutitermes corniger is
      suggested to be a good model for biogeographic and phylogeographic studies in the
      Neotropical Region. This study clarified the phylogeographic history of N.
      corniger and can contribute to the understanding of biogeographic dispersion
      processes in the Neotropical Region.

PMID- 29169319
TI  - Expression-based clustering of CAZyme-encoding genes of Aspergillus niger.
AB  - BACKGROUND: The Aspergillus niger genome contains a large repertoire of genes
      encoding carbohydrate active enzymes (CAZymes) that are targeted to plant
      polysaccharide degradation enabling A. niger to grow on a wide range of plant
      biomass substrates. Which genes need to be activated in certain environmental
      conditions depends on the composition of the available substrate. Previous
      studies have demonstrated the involvement of a number of transcriptional
      regulators in plant biomass degradation and have identified sets of target genes
      for each regulator. In this study, a broad transcriptional analysis was performed
      of the A. niger genes encoding (putative) plant polysaccharide degrading enzymes.
      Microarray data focusing on the initial response of A. niger to the presence of
      plant biomass related carbon sources were analyzed of a wild-type strain N402
      that was grown on a large range of carbon sources and of the regulatory mutant
      strains DeltaxlnR, DeltaaraR, DeltaamyR, DeltarhaR and DeltagalX that were grown
      on their specific inducing compounds. RESULTS: The cluster analysis of the
      expression data revealed several groups of co-regulated genes, which goes beyond
      the traditionally described co-regulated gene sets. Additional putative target
      genes of the selected regulators were identified, based on their expression
      profile. Notably, in several cases the expression profile puts questions on the
      function assignment of uncharacterized genes that was based on homology searches,
      highlighting the need for more extensive biochemical studies into the substrate
      specificity of enzymes encoded by these non-characterized genes. The data also
      revealed sets of genes that were upregulated in the regulatory mutants,
      suggesting interaction between the regulatory systems and a therefore even more
      complex overall regulatory network than has been reported so far. CONCLUSIONS:
      Expression profiling on a large number of substrates provides better insight in
      the complex regulatory systems that drive the conversion of plant biomass by
      fungi. In addition, the data provides additional evidence in favor of and against
      the similarity-based functions assigned to uncharacterized genes.

PMID- 29169321
TI  - LBJMR medium: a new polyvalent culture medium for isolating and selecting
      vancomycin and colistin-resistant bacteria.
AB  - BACKGROUND: Multi-drug resistant bacteria are a phenomenon which is on the
      increase around the world, particularly with the emergence of colistin-resistant
      Enterobacteriaceae and vancomycin-resistant enterococci strains. The recent
      discovery of a plasmid-mediated colistin resistance with the description of the
      transferable mcr-1 gene raised concerns about the need for an efficient detection
      method for these pathogens, to isolate infected patients as early as possible.
      The LBJMR medium was developed to screen for all polymyxin-resistant Gram
      negative bacteria, including mcr-1 positive isolates, and vancomycin-resistant
      Gram-positive bacteria. RESULTS: The LBJMR medium was developed by adding
      colistin sulfate salt at a low concentration (4 MUg/mL) and vancomycin (50
      MUg/mL), with glucose (7.5 g/L) as a fermentative substrate, to a Purple Agar
      Base (31 g/L). A total of 143 bacterial strains were used to evaluate this
      universal culture medium, and the sensitivity and specificity of detection were
      100% for the growth of resistant strains. 68 stool samples were cultured on
      LBJMR, and both colistin-resistant Gram-negative and vancomycin-resistant Gram
      positive strains were specifically detected. CONCLUSIONS: The LBJMR medium is a
      multipurpose selective medium which makes it possible to identify bacteria of
      interest from clinical samples and to isolate contaminated patients in hospital
      settings. This is a simple medium that could be easily used for screening in
      clinical microbiology laboratories.

PMID- 29169322
TI  - Evidence of high-altitude adaptation in the glyptosternoid fish,
      Creteuchiloglanis macropterus from the Nujiang River obtained through
      transcriptome analysis.
AB  - BACKGROUND: Organisms living at high altitudes face low oxygen and temperature
      conditions; thus, the genetic mechanisms underlying the adaptations in these
      organisms merit investigation. The glyptosternoid fish, Creteuchiloglanis
      macropterus mainly inhabits regions with gradual increases in altitudes along the
      Nujiang River and might serve as an appropriate evolutionary model for detecting
      adaptation processes in environments with altitude changes. RESULTS: We
      constructed eleven RNA-sequencing (RNA-seq) libraries of C. macropterus collected
      from five locations at different altitudes to identify the genetic signatures of
      high-altitude adaptation. The comparative genomic analysis indicated that C.
      macropterus has an accelerated evolutionary rate compared with that of fishes in
      the lowland, and fishes at higher altitudes might evolve faster. Functional
      enrichment analysis of the fast-evolving and positively selected genes,
      differentially expressed genes and highly expressed genes, showed that these
      genes were involved in many functions related to energy metabolism and hypoxia.
      CONCLUSIONS: Our study provides evidence of high-altitude adaptation in C.
      macropterus, and the detected adaptive genes might be a resource for future
      investigations of adaptations to high-altitude environments in other fishes.

PMID- 29169323
TI  - Tol2 transposon-mediated transgenesis in the Midas cichlid (Amphilophus
      citrinellus) - towards understanding gene function and regulatory evolution in an
      ecological model system for rapid phenotypic diversification.
AB  - BACKGROUND: The Midas cichlid species complex (Amphilophus spp.) is widely known
      among evolutionary biologists as a model system for sympatric speciation and
      adaptive phenotypic divergence within extremely short periods of time (a few
      hundred generations). The repeated parallel evolution of adaptive phenotypes in
      this radiation, combined with their near genetic identity, makes them an
      excellent model for studying phenotypic diversification. While many ecological
      and evolutionary studies have been performed on Midas cichlids, the molecular
      basis of specific phenotypes, particularly adaptations, and their underlying
      coding and cis-regulatory changes have not yet been studied thoroughly. RESULTS:
      For the first time in any New World cichlid, we use Tol2 transposon-mediated
      transgenesis in the Midas cichlid (Amphilophus citrinellus). By adapting existing
      microinjection protocols, we established an effective protocol for transgenesis
      in Midas cichlids. Embryos were injected with a Tol2 plasmid construct that
      drives enhanced green fluorescent protein (eGFP) expression under the control of
      the ubiquitin promoter. The transgene was successfully integrated into the
      germline, driving strong ubiquitous expression of eGFP in the first transgenic
      Midas cichlid line. Additionally, we show transient expression of two further
      transgenic constructs, ubiquitin::tdTomato and mitfa::eGFP. Transgenesis in Midas
      cichlids will facilitate further investigation of the genetic basis of species
      specific traits, many of which are adaptations. CONCLUSION: Transgenesis is a
      versatile tool not only for studying regulatory elements such as promoters and
      enhancers, but also for testing gene function through overexpression of allelic
      gene variants. As such, it is an important first step in establishing the Midas
      cichlid as a powerful model for studying adaptive coding and non-coding changes
      in an ecological and evolutionary context.

PMID- 29169324
TI  - A post-gene silencing bioinformatics protocol for plant-defence gene validation
      and underlying process identification: case study of the Arabidopsis thaliana
      NPR1.
AB  - BACKGROUND: Advances in forward and reverse genetic techniques have enabled the
      discovery and identification of several plant defence genes based on quantifiable
      disease phenotypes in mutant populations. Existing models for testing the effect
      of gene inactivation or genes causing these phenotypes do not take into account
      eventual uncertainty of these datasets and potential noise inherent in the
      biological experiment used, which may mask downstream analysis and limit the use
      of these datasets. Moreover, elucidating biological mechanisms driving the
      induced disease resistance and influencing these observable disease phenotypes
      has never been systematically tackled, eliciting the need for an efficient model
      to characterize completely the gene target under consideration. RESULTS: We
      developed a post-gene silencing bioinformatics (post-GSB) protocol which accounts
      for potential biases related to the disease phenotype datasets in assessing the
      contribution of the gene target to the plant defence response. The post-GSB
      protocol uses Gene Ontology semantic similarity and pathway dataset to generate
      enriched process regulatory network based on the functional degeneracy of the
      plant proteome to help understand the induced plant defence response. We applied
      this protocol to investigate the effect of the NPR1 gene silencing to changes in
      Arabidopsis thaliana plants following Pseudomonas syringae pathovar tomato strain
      DC3000 infection. Results indicated that the presence of a functionally active
      NPR1 reduced the plant's susceptibility to the infection, with about 99% of
      variability in Pseudomonas spore growth between npr1 mutant and wild-type
      samples. Moreover, the post-GSB protocol has revealed the coordinate action of
      target-associated genes and pathways through an enriched process regulatory
      network, summarizing the potential target-based induced disease resistance
      mechanism. CONCLUSIONS: This protocol can improve the characterization of the
      gene target and, potentially, elucidate induced defence response by more
      effectively utilizing available phenotype information and plant proteome
      functional knowledge.

PMID- 29169325
TI  - Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild
      type metastatic colorectal cancer.
AB  - BACKGROUND: In metastatic colorectal cancer, the location of the primary tumor
      has been suggested to have biological significance. In this study, we
      investigated whether primary tumor location affects cetuximab efficacy in
      patients with RAS wild-type metastatic colorectal cancer. METHODS: Genotyping by
      the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA,
      and BRAF was performed in tumors from 307 patients who had been given cetuximab
      as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those
      with multiple primary location (n = 10) were excluded. Right colon cancer was
      defined as a tumor located in the proximal part to splenic flexure. RESULTS: A
      total of 170 patients were included in the study (right versus left, 23 and 147,
      respectively). Patients with right colon cancer showed more mutated BRAF (39.1%
      vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs.
      3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and
      rectal cancer. Right colon cancer showed poorer progression-free survival (2.0
      vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P <
      0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF
      mutation, right colon primary, poorly differentiated histology, and peritoneal
      involvement were associated with risk of death. CONCLUSIONS: In RAS wild-type
      colon cancer treated with cetuximab as salvage treatment, right colon primary was
      associated with poorer survival outcomes than left colon and rectal cancer.

PMID- 29169326
TI  - Determinants of depression in primary caregivers of disabled older relatives: a
      path analysis.
AB  - BACKGROUND: Despite the large literature analysing factors related to depression,
      several factors such as caregiving obligation and the interrelationships among
      the different variables relating to depression have been little studied. The
      current study aimed to analyse the effect of caregiving obligation (beliefs
      regarding obligation and social pressure) on depression, and the mediating
      effects of perceived burden on the relationship between stressors and depression,
      in primary caregivers of older relatives. METHODS: Cross-sectional study design.
      A probabilistic sample of caregivers from Spain (N = 200) was used. The data
      collection was conducted in 2013 through structured interviews in the caregivers'
      homes. The measures included sense of obligation for caregiving, perceived
      burden, stressors and depression. RESULTS: Depression had a direct and positive
      association with perceived burden, behavioural problems, and social pressure, and
      it was indirectly related through perceived burden to behavioural problems,
      independence for the activities of daily living and beliefs of obligation.
      CONCLUSIONS: Our results support the multidimensional concept of obligation,
      suggesting the existence of both an external obligation (social pressure) and an
      internal obligation (beliefs of obligation); (b) our findings support the
      hypothesis that external obligation is related to negative caregiving
      consequences, while internal obligation protects from these consequences; and (c)
      our findings support the partial mediation of stressors on depression by
      perceived burden. The relevance of the research to clinical practice includes the
      importance of understanding the perceived obligation of caregiving related to
      both internal and external sources of obligation.

PMID- 29169328
TI  - Validation and inter-rater reliability of a three item falls risk screening tool.
AB  - BACKGROUND: Falls screening tools are routinely used in hospital settings and the
      psychometric properties of tools should be examined in the setting in which they
      are used. The aim of this study was to explore the concurrent and predictive
      validity of the Austin Health Falls Risk Screening Tool (AHFRST), compared with
      The Northern Hospital Modified St Thomas's Risk Assessment Tool (TNH-STRATIFY),
      and the inter-rater reliability of the AHFRST. METHODS: A research
      physiotherapist used the AHFRST and TNH-STRATIFY to classify 130 participants
      admitted to Austin Health (five acute wards, n = 115 two subacute wards n = 15;
      median length of stay 6 days IQR 3-12) as 'High' or 'Low' falls risk. The AHFRST
      was also completed by nursing staff on patient admission. Falls data was
      collected from the hospital incident reporting system. RESULTS: Six falls
      occurred during the study period (fall rate of 4.6 falls per 1000 bed days).
      There was substantial agreement between the AHFRST and the TNH-STRATIFY (Kappa =
      0.68, 95% CI 0.52-0.78). Both tools had poor predictive validity, with low
      specificity (AHFRST 46.0%, 95% CI 37.0-55.1; TNH-STRATIFY 34.7%, 95% CI 26.4
      43.7) and positive predictive values (AHFRST 5.6%, 95% CI 1.6-13.8; TNH-STRATIFY
      6.9%, 95% CI 2.6-14.4). The AHFRST showed moderate inter-rater reliability (Kappa
      = 0.54, 95% CI = 0.36-0.67, p < 0.001) although 18 patients did not have the
      AHFRST completed by nursing staff. CONCLUSIONS: There was an acceptable level of
      agreement between the 3 item AHFRST classification of falls risk and the longer,
      9 item TNH-STRATIFY classification. However, both tools demonstrated limited
      predictive validity in the Austin Health population. The results highlight the
      importance of evaluating the validity of falls screening tools, and the clinical
      utility of these tools should be reconsidered.

PMID- 29169327
TI  - Comparative transcriptome analysis of oil palm flowers reveals an EAR-motif
      containing R2R3-MYB that modulates phenylpropene biosynthesis.
AB  - BACKGROUND: Oil palm is the most productive oil crop and the efficiency of
      pollination has a direct impact on the yield of oil. Pollination by wind can
      occur but maximal pollination is mediated by the weevil E. kamerunicus. These
      weevils complete their life cycle by feeding on male flowers. Attraction of
      weevils to oil palm flowers is due to the emission of methylchavicol by both male
      and female flowers. In search for male flowers, the weevils visit female flowers
      by accident due to methylchavicol fragrance and deposit pollen. Given the
      importance of methylchavicol emission on pollination, we performed comparative
      transcriptome analysis of oil palm flowers and leaves to identify candidate genes
      involved in methylchavicol production in flowers. RESULTS: RNA sequencing (RNA
      Seq) of male open flowers, female open flowers and leaves was performed using
      Illumina HiSeq 2000 platform. Analysis of the transcriptome data revealed that
      the transcripts of methylchavicol biosynthesis genes were strongly up-regulated
      whereas transcripts encoding genes involved in lignin production such as, caffeic
      acid O-methyltransferase (COMT) and Ferulate-5-hydroxylase (F5H) were found to be
      suppressed in oil palm flowers. Among the transcripts encoding transcription
      factors, an EAR-motif-containing R2R3-MYB transcription factor (EgMYB4) was found
      to be enriched in oil palm flowers. We determined that EgMYB4 can suppress the
      expression of a monolignol pathway gene, EgCOMT, in vivo by binding to the AC
      elements present in the promoter region. EgMYB4 was further functionally
      characterized in sweet basil which also produces phenylpropenes like oil palm.
      Transgenic sweet basil plants showed significant reduction in lignin content but
      produced more phenylpropenes. CONCLUSIONS: Our results suggest that EgMYB4
      possibly restrains lignin biosynthesis in oil palm flowers thus allowing enhanced
      carbon flux into the phenylpropene pathway. This study augments our understanding
      of the diverse roles that EAR-motif-containing MYBs play to fine tune the
      metabolic flux along the various branches of core phenylpropanoid pathway. This
      will aid in metabolic engineering of plant aromatic compounds.

PMID- 29169329
TI  - Micro-costing analysis of guideline-based treatment by direct-acting agents: the
      real-life case of hepatitis C management in Brazil.
AB  - BACKGROUND: Eradication of hepatitis C virus (HCV) using direct-acting agents
      (DAA) has been associated with a financial burden to health authorities
      worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from
      the perspective of the Brazilian Ministry of Health (BMoH). METHODS: The activity
      based costing method was used to estimate the cost for monitoring/treatment of
      genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG
      IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or
      telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or
      simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars
      without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs
      were collected at the National Database of Health Prices and an overview of the
      literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens
      in real-world cohorts. RESULTS: Treatment costs of GT1-HCV patients were PPP$
      43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$ 71,196.03 (US$ 39,578.23) for PEG
      IFN/RBV/BOC and PPP$ 86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by
      all-oral interferon-free regimens were the less expensive approach: PPP$
      19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$ 21,590.91 (US$ 12,002.75) for
      SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96%
      for SOF/SIM. CONCLUSION: Strategies with all oral interferon-free might lead to
      lower costs for management of GT1-HCV patients compared to IFN-based regimens in
      Brazil. This occurred mainly because of high discounts over international DAA
      prices due to negotiation between BMoH and pharmaceutical industries.

PMID- 29169330
TI  - Comparing levocardia and dextrocardia in fetuses with heterotaxy syndrome:
      prenatal features, clinical significance and outcomes.
AB  - BACKGROUND: To investigate the differences in cardiovascular disease,
      extracardiac anomalies and outcomes between fetuses with levocardia and
      dextrocardia. METHODS: Clinical demographics, prenatal features, postnatal
      characteristics and the outcomes of fetuses with levocardia or dextrocardia were
      recorded and analyzed. RESULTS: Sixty-five fetuses with dextrocardia and thirty
      eight fetuses with levocardia were enrolled. Right ventricle outlet obstruction,
      atrioventricular septal defect and intestinal malrotation were common in both
      groups. Univentricular physiology, transposition of the great arteries and
      esophageal atresia were more frequent in fetuses with levocardia, whereas
      abnormal pulmonary venous connection, double outlet of right ventricle, left
      ventricle outlet obstruction and brain abnormalities were more frequent in the
      dextrocardia group. The accuracy of evaluating cardiac malformations was high,
      but the sensitivity in assessing extracardiac abnormalities was low. CONCLUSIONS:
      Although the disorders have certain overlapping features, there are several
      differences between fetuses with levocardia and dextrocardia. These findings
      might improve patient counseling and perinatal management.

PMID- 29169331
TI  - Prescription of secondary preventive drugs after ischemic stroke: results from
      the Malaysian National Stroke Registry.
AB  - BACKGROUND: Evaluation of secondary stroke prevention in low and middle-income
      countries remains limited. This study assessed the prescription of secondary
      preventive drugs among ischemic stroke patients upon hospital discharge in
      Malaysia and identified factors related to the prescribing decisions. METHODS:
      From Malaysian National Stroke Registry, we included patients with non-fatal
      ischemic stroke. Prescriptions of antiplatelet, anticoagulants, antihypertensive
      drugs and lipid-lowering drugs were assessed. Multi-level logistic regressions
      were performed to determine the relation between potential factors and drug
      prescriptions. RESULTS: Of 5292 patients, 48% received antihypertensive drugs,
      88.9% antiplatelet and 88.7% lipid-lowering drugs upon discharge. Thirty-three
      percent of patients with an indication for anticoagulants (n = 391) received it.
      Compared to patients <=50 years, patients above 70 years were less likely to
      receive antiplatelet (OR: 0.72, 95% CI: 0.50-1.03), lipid-lowering drugs (OR:
      0.66, 95% CI: 0.45-0.95) and anticoagulants (OR: 0.27, 95% CI: 0.09-0.83).
      Patients with moderate to severe disability upon discharge had less odds of
      receiving secondary preventive drugs; an odds ratio of 0.57 (95% CI: 0.45-0.71)
      for antiplatelet, 0.86 (95% CI: 0.75-0.98) for antihypertensive drugs and 0.78
      (95% CI: 0.63-0.97) for lipid-lowering drugs in comparison to those with minor
      disability. Having prior specific comorbidities and drug prescriptions
      significantly increased the odds of receiving these drugs. No differences were
      found between sexes and ethnicities. CONCLUSIONS: Prescription of
      antihypertensive drugs and anticoagulants among ischemic stroke patients in
      Malaysia were suboptimal. Efforts to initiate regular clinical audits to evaluate
      the uptake and effectiveness of secondary preventive strategies are timely in low
      and middle-income settings.

PMID- 29169332
TI  - How does pre-dialysis education need to change? Findings from a qualitative study
      with staff and patients.
AB  - BACKGROUND: Pre-dialysis education (PDE) is provided to thousands of patients
      every year, helping them decide which renal replacement therapy (RRT) to choose.
      However, its effectiveness is largely unknown, with relatively little previous
      research into patients' views about PDE, and no research into staff views. This
      study reports findings relevant to PDE from a larger mixed methods study,
      providing insights into what staff and patients think needs to improve. METHODS:
      Semi-structured interviews in four hospitals with 96 clinical and managerial
      staff and 93 dialysis patients, exploring experiences of and views about PDE, and
      analysed using thematic framework analysis. RESULTS: Most patients found PDE
      helpful and staff valued its role in supporting patient decision-making. However,
      patients wanted to see teaching methods and materials improve and biases
      eliminated. Staff were less aware than patients of how informal staff-patient
      conversations can influence patients' treatment decision-making. Many staff felt
      ill equipped to talk about all treatment options in a balanced and unbiased way.
      Patient decision-making was found to be complex and patients' abilities to make
      treatment decisions were adversely affected in the pre-dialysis period by
      emotional distress. CONCLUSIONS: Suggested improvements to teaching methods and
      educational materials are in line with previous studies and current clinical
      guidelines. All staff, irrespective of their role, need to be trained about all
      treatment options so that informal conversations with patients are not biased.
      The study argues for a more individualised approach to PDE which is more like
      counselling than education and would demand a higher level of skill and training
      for specialist PDE staff. The study concludes that even if these improvements are
      made to PDE, not all patients will benefit, because some find decision-making in
      the pre-dialysis period too complex or are unable to engage with education due to
      illness or emotional distress. It is therefore recommended that pre-dialysis
      treatment decisions are temporary, and that PDE is replaced with on-going RRT
      education which provides opportunities for personalised education and on-going
      review of patients' treatment choices. Emotional support to help overcome the
      distress of the transition to end-stage renal disease will also be essential to
      ensure all patients can benefit from RRT education.

PMID- 29169333
TI  - Cultural factors associated with the intent to be screened for prostate cancer
      among adult men in a rural Kenyan community.
AB  - BACKGROUND: The aim of this study was to determine cultural factors associated
      with prostate cancer screening intent among adult Kenyan African men. METHODS: A
      cross-sectional quantitative study with an analytic design was carried out in a
      randomly selected sample of 155 adult men aged 25-98 years living in a rural
      community in Kenya. Constructs from the Theory of Planned Behaviour were used to
      guide this study. A 5 -point Likert scale was used to assess fatalistic beliefs,
      fear, perceived benefits, and family influence. A structured questionnaire was
      used to collect quantitative data at the household level. RESULTS: Only 2.4% of
      the study participants had been screened for prostate cancer. About 2/3rd (64%)
      of the participants felt that they were at risk of getting prostate cancer; 44%
      intended to be screened within the following 6 months. Mean scores on a 5-point
      Likert scale indicated: strong beliefs in the benefits of prostate screening (4.2
      (+/-SD .8), men aged over 40 were not perceived to be at risk of getting prostate
      cancer (1.3 +/- .6), relatively high fatalistic beliefs of prostate cancer
      screening (3.6 (+/-SD .8), high degree of fear or apprehension of prostate cancer
      screening (3.2 (+/-SD 1.2), and a high level of influence of family members in
      prostate cancer screening (3.9 (+/-SD 1.0). The Wald criterion demonstrated that
      only family influence made a significant contribution to the intent to screen for
      prostate cancer (p = 0.031). Age, education, marital status, fatalism, fear, and
      benefit of screening were not associated with the intent to screen for prostate
      cancer. CONCLUSIONS: Strong beliefs of the benefits of prostate screening tended
      to be surpassed by relatively high fatalistic beliefs and fear or apprehension in
      prostate cancer screening. The family plays an important role in influencing
      decision making related to prostate cancer screening in Africans.

PMID- 29169334
TI  - Prevalence and treatment of diabetes mellitus and hypertension among older adults
      with intellectual disability in comparison with the general population.
AB  - BACKGROUND: Diabetes mellitus and hypertension are risk factors for
      cardiovascular disease, which is the most common cause of death in the world.
      People with intellectual disability (ID) have been reported to have high rates of
      both these disorders. The aim of this study was to describe and compare
      prevalence ratios of diabetes mellitus and hypertension between older adults with
      ID and their age peers in the general population, and to describe and compare
      treatment patterns in these two groups. METHODS: This is a Swedish register-based
      study, in which we established a cohort of people aged 55+ years and who had
      received support for those with ID in 2012 (n = 7936). We also established a same
      sized referent cohort from the general population matched by sex and year of
      birth. Information on diagnoses of diabetes mellitus and hypertension, and
      prescription of drugs for these disorders, were collected from national registers
      for the period 2006-2012. The two cohorts were compared using generalized linear
      models (GLM). RESULTS: People with ID were 20% more likely than the general
      population to have a diagnosis of diabetes mellitus, and 26% more likely to have
      prescription of drugs for diabetes mellitus. People in the general population
      were 81% more likely to have a diagnosis of hypertension, and 9% more likely to
      have a prescription of drugs for hypertension. Among those with diabetes, ID was
      associated with higher occurrence of prescription of insulin combination drugs
      and sulfonylureas, but lower occurrence of prescription of dipeptidyl peptidase
      (DPP) 4-inhibitors and exenatide/liraglutide. Among those with hypertension, ID
      was associated with higher occurrence of prescription of diuretics, but lower
      occurrence of prescription of calcium channel blockers and angiotensin II
      antagonists. CONCLUSIONS: Treatment regimens among people with ID tended to
      include older types of medication compared with what was prescribed in the
      general population. To ensure that this is medically appropriate and not due to
      failure to update the treatment regimen, it is important to investigate if the
      people with ID and diabetes mellitus or hypertension are subjected to the same
      regular drug reviews that are recommended for older adults in general.

PMID- 29169335
TI  - Patient- and treatment-related risk factors associated with neck muscle spasm in
      nasopharyngeal carcinoma patients after intensity-modulated radiotherapy.
AB  - BACKGROUND: To evaluate the incidence of neck muscle spasm in nasopharyngeal
      carcinoma (NPC) patients that received intensity-modulated radiotherapy (IMRT),
      and to analyse the patient- and treatment-related risk factors associated with
      neck muscle spasm. METHODS: A sample of 152 IMRT-treated, biopsy-proven,
      nondisseminated NPC patients were retrospectively analysed. All had documented
      IMRT treatment plans and had returned for follow-up review at 4 years post
      radiotherapy. Spasm of the sternocleidomastoid (SCM) muscle was graded from 0 to
      3 (absent to severe) and this grade served as the clinical endpoint. Risk factors
      were identified using logistic regression analysis. RESULTS: Within 4 years of
      radiotherapy, neck muscle spasm developed in 23.68% of the patients; Grades 0, 1,
      2 and 3 were respectively assigned to 83.55, 7.57, 6.58 and 2.30% of assessed
      SCMs. Multivariate analysis indicated that gender, N stage, V60 (percentage of
      SCM volume that received >60 Gy) were independent prognostic variables, and that
      the optimal threshold for using V60 to predict neck muscle spasm was 61.92%
      (sensitivity = 0.900, specificity = 0.953). CONCLUSIONS: Gender, N stage and V60
      were independent predictive factors for post-radiotherapy neck muscle spasm, and
      a V60 of <=61.92% in the SCM was relatively safe.

PMID- 29169336
TI  - Multi-region and single-cell sequencing reveal variable genomic heterogeneity in
      rectal cancer.
AB  - BACKGROUND: Colorectal cancer is a heterogeneous group of malignancies with
      complex molecular subtypes. While colon cancer has been widely investigated,
      studies on rectal cancer are very limited. Here, we performed multi-region whole
      exome sequencing and single-cell whole-genome sequencing to examine the genomic
      intratumor heterogeneity (ITH) of rectal tumors. METHODS: We sequenced nine tumor
      regions and 88 single cells from two rectal cancer patients with tumors of the
      same molecular classification and characterized their mutation profiles and
      somatic copy number alterations (SCNAs) at the multi-region and the single-cell
      levels. RESULTS: A variable extent of genomic heterogeneity was observed between
      the two patients, and the degree of ITH increased when analyzed on the single
      cell level. We found that major SCNAs were early events in cancer development and
      inherited steadily. Single-cell sequencing revealed mutations and SCNAs which
      were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer
      at regional and single-cell resolution and demonstrated that variable
      heterogeneity existed in two patients. The mutational scenarios and SCNA profiles
      of two patients with treatment naive from the same molecular subtype are quite
      different. CONCLUSIONS: Our results suggest each tumor possesses its own
      architecture, which may result in different diagnosis, prognosis, and drug
      responses. Remarkable ITH exists in the two patients we have studied, providing a
      preliminary impression of ITH in rectal cancer.

PMID- 29169338
TI  - Anger management in substance abuse based on cognitive behavioral therapy: an
      interventional study.
AB  - BACKGROUND: Anger and aggression have been developing notably in societies,
      especially among patients depending on substance abuse. Therefore, this study
      aimed to investigate the effect of anger management based on group education
      among patients depending on substances according to Patrick Reilly's cognitive
      behavioral approach. METHODS: In a quasi- experimental study, all patients who
      met the inclusion criteria were evaluated regarding their aggression level. The
      participants were assigned to 12 educational sessions based on group therapy and
      Patrick-Reilly's anger management by focusing on using a combination of cognitive
      intervention, relaxation, and communication skills. The data were analyzed using
      the SPSS statistical software, version 16. RESULTS: The findings showed a
      significant difference between the two groups regarding aggression level after
      the intervention (p = 0.001). No significant relationship was observed between
      aggression level and demographic variables (p > 0.05). CONCLUSION: The
      intervention of this study can be used for establishing self-management and
      decreasing anger among patients depending on substances. They can also be used as
      a therapeutic program in addition to pharmacotherapy. TRIAL REGISTRATION:
      IRCT2016102030398N1 .

PMID- 29169337
TI  - Minimally invasive pancreaticoduodenectomy for periampullary disease: a
      comprehensive review of literature and meta-analysis of outcomes compared with
      open surgery.
AB  - BACKGROUND: Minimally invasive pancreatoduodenectomy (MIPD) has been gradually
      attempted. However, whether MIPD is superior, equal or inferior to its
      conventional open pancreatoduodenectomy (OPD) is not clear. METHODS: Studies
      published up to May 2017 were searched in PubMed, Embase, Cochrane Library, and
      Web of Science. Main outcomes were comprehensively reviewed and measured
      including conversion to open approach, operation time (OP), estimated blood loss
      (EBL), transfusion, length of hospital stay (LOS), overall complications,
      postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), post
      pancreatectomy hemorrhage (PPH), readmission, reoperation and reasons of
      preoperative death, number of retrieved lymph nodes (RLN), surgical margins,
      recurrence, and survival. The software of Review Manage version 5.1 was used for
      meta-analysis. RESULTS: One hundred studies were included for systematic review
      and 26 out of them (totally 3402 cases, 1064 for MIPD, 2338 for OPD) were
      included for meta-analysis. In the early years, most articles were case reports
      or non-control case series studies, while in the last 6 years high-volume and
      comparative researches were increasing gradually. Systematic review revealed
      conversion rates of MIPD to OPD ranged from 0% to 40%. The mean or median OP of
      MIPD ranged from 276 to 657 min. The total POPF rates vary between 3.8% and 50%
      observed in all systematic reviewed studies. Meta-analysis demonstrated MIPD had
      longer OP (WMD = 99.4 min; 95%CI: 46.0 ~ 152.8, P < 0.01), lower blood loss (WMD
      = -0.54 ml; 95% CI, -0.88 ~ -0.20 ml; P < 0.01), lower transfusion rate (RR =
      0.73, 95%CI: 0.57 ~ 0.94, P = 0.02), shorter LOS (WMD = -3.49 days; 95%CI: -4.83
      ~ -2.15, P < 0.01). There was no significant difference in time to oral intake,
      postoperative complications, POPF, reoperation, readmission, perioperative
      mortality and number of retrieved lymph nodes. CONCLUSION: Our study demonstrates
      MIPD is technically feasible and safety on the basis of historical studies. MIPD
      is associated with less blood loss, faster postoperative recovery, shorter length
      of hospitalization and longer operation time. These findings are waiting for
      being confirmed with robust prospective comparative studies and randomized
      clinical trials.

PMID- 29169339
TI  - An orthotopic xenograft model for high-risk non-muscle invasive bladder cancer in
      mice: influence of mouse strain, tumor cell count, dwell time and bladder
      pretreatment.
AB  - BACKGROUND: Novel theranostic options for high-risk non-muscle invasive bladder
      cancer are urgently needed. This requires a thorough evaluation of experimental
      approaches in animal models best possibly reflecting human disease before
      entering clinical studies. Although several bladder cancer xenograft models were
      used in the literature, the establishment of an orthotopic bladder cancer model
      in mice remains challenging. METHODS: Luciferase-transduced UM-UC-3LUCK1 bladder
      cancer cells were instilled transurethrally via 24G permanent venous catheters
      into athymic NMRI and BALB/c nude mice as well as into SCID-beige mice. Besides
      the mouse strain, the pretreatment of the bladder wall (trypsin or poly-L
      lysine), tumor cell count (0.5 * 106-5.0 * 106) and tumor cell dwell time in the
      murine bladder (30 min - 2 h) were varied. Tumors were morphologically and
      functionally visualized using bioluminescence imaging (BLI), magnetic resonance
      imaging (MRI), and positron emission tomography (PET). RESULTS: Immunodeficiency
      of the mouse strains was the most important factor influencing cancer cell
      engraftment, whereas modifying cell count and instillation time allowed fine
      tuning of the BLI signal start and duration - both representing the possible
      treatment period for the evaluation of new therapeutics. Best orthotopic tumor
      growth was achieved by transurethral instillation of 1.0 * 106 UM-UC-3LUCK1
      bladder cancer cells into SCID-beige mice for 2 h after bladder pretreatment with
      poly-L-lysine. A pilot PET experiment using 68Ga-cetuximab as transurethrally
      administered radiotracer revealed functional expression of epidermal growth
      factor receptor as representative molecular characteristic of engrafted cancer
      cells in the bladder. CONCLUSIONS: With the optimized protocol in SCID-beige mice
      an applicable and reliable model of high-risk non-muscle invasive bladder cancer
      for the development of novel theranostic approaches was established.

PMID- 29169340
TI  - Situational analysis of antibiotic use and resistance in Ghana: policy and
      regulation.
AB  - BACKGROUND: Antibiotics have played an essential role in decreasing morbidity and
      mortality from infectious diseases. However, indiscriminate use and unrestricted
      access is contributing to the emergence of bacterial resistance. This paper
      reports on a situational analysis of antimicrobial use and resistance in Ghana,
      with focus on policy and regulation. METHODS: Relevant policy documents, reports,
      regulations and enactments were reviewed. PubMed and Google search engines were
      used to extract relevant published papers. Websites of stakeholders such as
      Ministry of Health (MOH) and its agencies were also reviewed. An interview guide
      was used to elicit responses from selected officials from these sectors. RESULTS:
      Laws and guidelines to control the use of antimicrobials in humans were available
      but not for animals. There was no National Antimicrobial Policy (NAP). A health
      practice regulatory law mandates Physicians, Physician Assistants, Midwives and
      trained Nurses to prescribe antimicrobials. However, antibiotics are widely
      prescribed and dispensed by unauthorised persons, suggesting weak enforcement of
      the laws. Antibiotics were also supplied to and from unapproved medicine outlets.
      The Standard Treatment Guidelines (STG), Essential Medicines List (EML) and the
      National Health Insurance Scheme Medicines List (NHISML) provide restrictions
      regarding levels of prescribing of antimicrobials. However, existing guidelines
      on antibiotic use are mostly not adhered to. The use of Automatic Stop Orders to
      avoid wastage in the hospitals is also not practiced. Data on use of antibiotics
      for individuals are not readily available in most facilities. Again, there are no
      standards or guidelines on veterinary use of antibiotics. Surveillance systems
      for consumption of antibiotics and resistance monitoring were not in place in
      most health facilities. However, there is an ongoing national action to create
      awareness on bacteria resistance, strengthening knowledge through research and
      surveillance and development of NAP in line with global action plan on
      antimicrobial resistance. CONCLUSION: Absence of national antimicrobial policy,
      weak regulatory environment and non-adherence to practice standards may have
      contributed to increased and unregulated access to antimicrobials in Ghana, a
      catalyst for development and spread of antimicrobial resistance.

PMID- 29169341
TI  - Prevalence, genetic variants and clinical implications of G-6-PD deficiency in
      Burkina Faso: a systematic review.
AB  - BACKGROUND: It is now well-known that some antimalarials such as primaquine may
      induce severe hemolytic anemia in people with G-6-PD deficiency. Antimalarial
      drug prescriptions must, therefore take into account the patient's G-6-PD status
      in malaria endemic areas such as Burkina Faso, where the prevalence of this
      genetic abnormality is relatively high. Although great clinical heterogeneity is
      observed depending on the molecular nature of the deficiency and the residual
      enzyme activity in the red blood cell, there is very poor data on the prevalence
      of G-6-PD deficiency and the distribution of involved genetic variants in Burkina
      Faso. In this systematic review, we present a synthesis of the various studies
      carried out on the G-6-PD deficiency in Burkina Faso in order to determine its
      prevalence, probable distribution of the genetic variants involved and their
      clinical implications for a national systematic screening policy among the groups
      most vulnerable to malaria. METHODS: A systematic review was carried out to
      analyze available published data on the prevalence, phenotypes and mutations
      responsible for G-6-PD deficiency in Burkina Faso. The key words used were "G-6
      PD deficiency AND Burkina Faso" or "Deficit en G-6-PD AND Burkina Faso" in
      French. To identify the relevant articles, two independent reviewers reviewed the
      titles, abstracts and the full text of the selected papers. RESULTS: An average
      prevalence of 16.6% (183/1100; CI 95%: 0.145-0.190) and 6.5% (69/1066; CI 95%:
      0.051-0.081) of G-6-PD deficiency was found respectively in men and women in this
      systematic review. Although the predominance (99.8% of G-6-PD deficient cases) of
      202A/376G G-6-PD A- variant, the Santamaria and Betica Selma variants were
      identified in Burkina Faso. Independently of the method used, the enzymatic
      deficiency was significantly higher in males (2.5-20.5%) compared to females (3.3
      12.3%). CONCLUSION: This systematic review suggests that despite the ubiquity of
      the 202A/376G G-6-PD A- variant in Burkina Faso, it will be necessary to consider
      the Santamaria and Betica Selma variants although their frequencies remain to be
      specified. A systematic screening of the G-6-PD deficiency is also needed to
      prevent the occurrence of iatrogenic hemolytic accidents.

PMID- 29169342
TI  - MVQTLCIM: composite interval mapping of multivariate traits in a hybrid F1
      population of outbred species.
AB  - BACKGROUND: With the plummeting cost of the next-generation sequencing
      technologies, high-density genetic linkage maps could be constructed in a forest
      hybrid F1 population. However, based on such genetic maps, quantitative trait
      loci (QTL) mapping cannot be directly conducted with traditional statistical
      methods or tools because the linkage phase and segregation pattern of molecular
      markers are not always fixed as in inbred lines. RESULTS: We implemented the
      traditional composite interval mapping (CIM) method to multivariate trait data in
      forest trees and developed the corresponding software, mvqtlcim. Our method not
      only incorporated the various segregations and linkage phases of molecular
      markers, but also applied Takeuchi's information criterion (TIC) to discriminate
      the QTL segregation type among several possible alternatives. QTL mapping was
      performed in a hybrid F1 population of Populus deltoides and P. simonii, and 12
      QTLs were detected for tree height over 6 time points. The software package
      allowed many options for parameters as well as parallel computing for permutation
      tests. The features of the software were demonstrated with the real data analysis
      and a large number of Monte Carlo simulations. CONCLUSIONS: We provided a
      powerful tool for QTL mapping of multiple or longitudinal traits in an outbred F1
      population, in which the traditional software for QTL mapping cannot be used.
      This tool will facilitate studying of QTL mapping and thus will accelerate
      molecular breeding programs especially in forest trees. The tool package is
      freely available from https://github.com/tongchf /mvqtlcim.

PMID- 29169343
TI  - "What do you know?"--knowledge among village doctors of lead poisoning in
      children in rural China.
AB  - BACKGROUND: This study evaluates the extent of village doctors' knowledge of lead
      poisoning in children in rural China and assesses the characteristics associated
      with possessing accurate knowledge. METHODS: A cross-sectional, questionnaire
      based survey of 297 village doctors in Fenghuang County, Hunan Province, China
      was conducted. All village doctors were interviewed face-to-face using a "What do
      you know" test questionnaire focusing on prevention strategies and lead sources
      in rural children. RESULTS: A total of 287 (96.6%) village doctors completed the
      survey in full. Most village doctors had an appropriate degree of general
      knowledge of lead poisoning; however, they had relatively poor knowledge of lead
      sources and prevention measures. Village doctors with an undergraduate level
      education scored an average of 2.7 points higher than those who had a junior
      college level education (p = 0.033). Village doctors with an annual income <=
      10,000 RMB yuan scored 1.03 points lower than those whose income was >10,001 RMB
      yuan. Ethnic Han village doctors scored 1.12 points higher, on average, than
      ethnic Tujia village doctors (p = 0.027). CONCLUSIONS: This study identified
      important gaps in knowledge concerning lead poisoning in children among a rural
      population of village doctors. There is a clear need for multifaceted
      interventions that target village doctors to improve their knowledge regarding
      lead poisoning in children. The "What do you know" questionnaire is a new tool to
      evaluate lead poisoning knowledge and education projects.

PMID- 29169344
TI  - Genome-wide association mapping of black point reaction in common wheat (Triticum
      aestivum L.).
AB  - BACKGROUND: Black point is a serious threat to wheat production and can be
      managed by host resistance. Marker-assisted selection (MAS) has the potential to
      accelerate genetic improvement of black point resistance in wheat breeding. We
      performed a genome-wide association study (GWAS) using the high-density wheat 90
      K and 660 K single nucleotide polymorphism (SNP) assays to better understand the
      genetic basis of black point resistance and identify associated molecular
      markers. RESULTS: Black point reactions were evaluated in 166 elite wheat
      cultivars in five environments. Twenty-five unique loci were identified on
      chromosomes 2A, 2B, 3A, 3B (2), 3D, 4B (2), 5A (3), 5B (3), 6A, 6B, 6D, 7A (5),
      7B and 7D (2), respectively, explaining phenotypic variation ranging from 7.9 to
      18.0%. The highest number of loci was detected in the A genome (11), followed by
      the B (10) and D (4) genomes. Among these, 13 were identified in two or more
      environments. Seven loci coincided with known genes or quantitative trait locus
      (QTL), whereas the other 18 were potentially novel loci. Linear regression showed
      a clear dependence of black point scores on the number of favorable alleles,
      suggesting that QTL pyramiding will be an effective approach to increase
      resistance. In silico analysis of sequences of resistance-associated SNPs
      identified 6 genes possibly involved in oxidase, signal transduction and stress
      resistance as candidate genes involved in black point reaction. CONCLUSION: SNP
      markers significantly associated with black point resistance and accessions with
      a larger number of resistance alleles can be used to further enhance black point
      resistance in breeding. This study provides new insights into the genetic
      architecture of black point reaction.

PMID- 29169345
TI  - The antioxidant effects of riluzole on the APRE-19 celll model injury-induced by
      t-BHP.
AB  - BACKGROUND: Age-related macular degeneration (AMD) causes the dysfunction of the
      retinal pigment epithelial (RPE) cells. In this study, we examined the effects of
      riluzole, a sustained activator of the TRAAK potassium channel, on human RPE
      (ARPE-19) cells in an oxidant-induced cell-injury model and elucidate the
      mechanism of riluzole on RPE cell apoptosis. METHODS: The follow four groups of
      ARPE-19 cells were treated with riluzole and/or tert-butyl hydroperoxide (t-BHP)
      for 24.0 h: control, t-BHP, riluzole, and t-BHP + riluzole. Cell apoptosis was
      measured by flow cytometry, and Western blotting was performed to analyze the
      expression of the weakly inward rectifying potassium (TRAAK) channel. Finally,
      the mitochondrial membrane potential (Deltapsim) was detected by flow cytometry,
      and cytochrome C (Cyt-c) release was assessed by Western blotting. RESULTS: The
      viability of the cells in the cotreated group was significantly higher (85.6 +/-
      3.1%) than that in the t-BHP group (66.2 +/- 2.5%). In addition, the cells in the
      cotreated group had a higher effect on increasing the expression of TRAAK than
      the t-BHP group. The results also showed that Cyt-c translocation significantly
      decreased and Deltapsim increased in the cotreated group. CONCLUSIONS: These
      results demonstrate that riluzole protects RPE cells from apoptosis. The
      protection mechanism of riluzole could be from stabilizing mitochondrial
      Deltapsim and preventing the release of Cyt-c. Changes in TRAAK expression might
      also contribute to the protection of RPE cells.

PMID- 29169347
TI  - Intermediate PSA half-life after neoadjuvant hormone therapy predicts reduced
      risk of castration-resistant prostate cancer development after radical
      prostatectomy.
AB  - BACKGROUND: The magnitude and rapidity of the tumor response to androgen
      deprivation is known to predict the durability of the therapy. We have
      investigated the predictive value of categorizing patients by the half-life of
      PSA under neoadjuvant androgen deprivation therapy in patients with biochemical
      recurrence after radical prostatectomy. METHODS: Medical records of 317 patients
      who received neoadjuvant androgen deprivation therapy before radical
      prostatectomy and developed biochemical recurrence were analyzed. The patients
      were categorized into five groups according to PSA half-life. Risk of developing
      castration resistance was evaluated by Kaplan-Meier analysis and by Cox
      proportional risk regression analysis. RESULTS: The median follow-up duration was
      50.1 months (IQR 31.8-68.7) and median PSA half-life was 22.1 days (IQR 12.7
      38.4). Comparison of survival curves revealed that patients in the intermediate
      response group showed significantly lower 5-year castration-resistant prostate
      cancer rate (37.5%) compared to non-response and ultra-rapid response groups
      (63.6%, p = 0.007; 56.1%, p = 0.031; respectively). In the multivariate
      regression model, intermediate response compared to non-response was associated
      with significantly reduced risk of castration resistance development (hazard
      ratio 0.397, 95% confidence interval 0.191-0.823, p = 0.013) and overall
      mortality (hazard ratio 0.138, 95% confidence interval 0.033-0.584, p = 0.007).
      When subcategorized by Gleason score, Kaplan-Meier curve revealed that, in the
      high Gleason score stratum, 5-year castration-resistant prostate cancer rate for
      intermediate response group (44.0%) was exceptionally lower than that in non
      response group (66.7%, p = 0.047), while castration resistance increased in other
      groups. CONCLUSION: Short PSA half-life as well as no response after androgen
      deprivation is associated with increased risk of treatment failure compared to
      intermediate PSA half-life.

PMID- 29169346
TI  - Social and clinical determinants of preferences and their achievement at the end
      of life: prospective cohort study of older adults receiving palliative care in
      three countries.
AB  - BACKGROUND: Achieving choice is proposed as a quality marker. But little is known
      about what influences preferences especially among older adults. We aimed to
      determine and compare, across three countries, factors associated with
      preferences for place of death and treatment, and actual site of death. METHODS:
      We recruited adults aged >=65-years from hospital-based multiprofessional
      palliative care services in London, Dublin, New York, and followed them for >17
      months. All services offered consultation on hospital wards, support for existing
      clinical teams, outpatient services and received funding from their National
      Health Service and/or relevant Insurance reimbursements. The New York service
      additionally had 10 inpatient beds. All worked with and referred patients to
      local hospices. Face-to-face interviews recorded most and least preferred place
      of death, treatment goal priorities, demographic and clinical information using
      validated questionnaires. Multivariable and multilevel analyses assessed
      associated factors. RESULTS: One hundred and thirty eight older adults (64
      London, 59 Dublin, 15 New York) were recruited, 110 died during follow-up. Home
      was the most preferred place of death (77/138, 56%) followed by inpatient
      palliative care/hospice units (22%). Hospital was least preferred (35/138, 25%),
      followed by nursing home (20%) and home (16%); hospice/palliative care unit was
      rarely least preferred (4%). Most respondents prioritised improving quality of
      life, either alone (54%), or equal with life extension (39%); few (3%) chose only
      life extension. There were no significant differences between countries. Main
      associates with home preference were: cancer diagnosis (OR 3.72, 95% CI 1.40
      9.90) and living with someone (OR 2.19, 1.33-3.62). Adults with non-cancer
      diagnoses were more likely to prefer palliative care units (OR 2.39, 1.14-5.03).
      Conversely, functional independence (OR 1.05, 1.04-1.06) and valuing quality of
      life (OR 3.11, 2.89-3.36) were associated with dying at home. There was a
      mismatch between preferences and achievements - of 85 people who preferred home
      or a palliative care unit, 19 (25%) achieved their first preference. CONCLUSION:
      Although home is the most common first preference, it is polarising and for 16%
      it is the least preferred. Inpatient palliative care unit emerges as the second
      most preferred place, is rarely least preferred, and yet was often not achieved
      for those who wanted to die there. Factors affecting stated preferences and met
      preferences differ. Available services, notably community support and palliative
      care units, require expansion. Contrasting actual place of death with capacity
      for meeting patient and family needs may be a better quality indicator than
      simply 'achieved preferences'.

PMID- 29169348
TI  - Inpatient satisfaction with medical information received from caregivers: an
      observational study on the effect of social deprivation.
AB  - BACKGROUND: The main objective of this study was to explore the relationships
      between inpatients' social differentiation and satisfaction with the medical
      information delivered by caregivers. METHODS: In four departments of a teaching
      hospital, patients were enrolled as well as their attending physician and one of
      the nurses assigned to them. Structured survey questionnaires were administered
      face-to-face to patients and caregivers. Patients were asked to rate their
      satisfaction with the medical information received, the quality and duration of
      the interactions with the caregivers, and their experience regarding their
      involvement in medical decision-making. Caregivers were asked to rate their
      perception of the patients' social position and involvement in medical decision
      making. Social deprivation was assessed using the EPICES score in particular. The
      statistical analysis was mainly descriptive and completed by a structural
      equation model. RESULTS: A sample of 255 patients, 221 pairs of patient-physician
      and 235 pairs of patient-nurse were considered. One third of the patients (32.7%)
      were identified as socially deprived. They were significantly less satisfied with
      the information they received on their health status or their treatment; 56.7% of
      patients thought that they received sufficient explanations without having to
      ask. This proportion was significantly lower in socially deprived patients
      (42.3%) compared to not deprived patients (63.6%, p < 0.01). Patients' reported
      involvement in medical decision-making was significantly lower for socially
      deprived patients (75.0% vs 89.0%, p < 0.001). The structural equation model
      showed that the main determinant of patients' satisfaction regarding medical
      information was their perceived involvement in informed medical decision-making
      (CFI = 0.998, RMSEA = 0.022). CONCLUSIONS: These findings suggest that physicians
      and nurses need training on communication targeted towards vulnerable patients,
      in order to improve the accessibility of medical information, and thus to reduce
      health inequalities.

PMID- 29169349
TI  - Anticholinesterase and antioxidant potentials of Nonea micrantha Bioss. & Reut
      along with GC-MS analysis.
AB  - BACKGROUND: Nonea micrantha Boiss. & Reut . being an unexplored member of
      Boraginaceae was investigated for GC/MS analysis, acetylcholinesterase (AChE),
      butyrylcholinesterase (BChE) inhibitory and antioxidant activities in an attempt
      to find its effectiveness in neurological disorders. METHODS: The AChE and BChE
      inhibitory activities of crude methanolic extract (Nm.Cr), subsequent fractions;
      n-hexane (Nm.Hex), chloroform (Nm.Cf), ethyl acetate (Nm.EtAc), aqueous (Nm.Aq)
      and crude saponins (Nm.Sp) from N. micrantha were conducted using Ellman's assay.
      The antioxidant activity of the plant samples using DPPH and ABTS free radical
      scavenging potential following quantitative spectrophotometric and qualitative
      TLC method were also studied. Moreover the total reducing power (TRP) of all the
      samples was also figured out. RESULTS: The GC/Ms analysis confirmed that the
      plant is rich in bioactive molecules. Among different fractions, Nm.Hex, Nm.EtAc
      and Nm.Cf exhibited highest AChE inhibitory activities causing 75.51 +/- 0.73,
      68.54 +/- 0.59 and 63.48 +/- 0.59% enzyme inhibition respectively and IC50 of 44,
      100 and 144 MUg/mL respectively. In BChE inhibiton assay, Nm.Aq, Nm.Sp and Nm.Cr
      showed highest activity causing 83.49 +/- 0.27, 81.49 +/- 0.89 and 75.31 +/-
      0.56% enzyme inhibition with IC50 of 90, 110 and 44 MUg/mL respectively. In DPPH
      assay, Nm.Aq, Nm.Cf, Nm.Hex and Nm.Cr were most potent exhibiting IC50 values of
      3, 5, 93 and 120 MUg/ml respectively. In ABTS assay Nm.EtAc, Nm.Aq, Nm.Sp and
      Nm.Cr showed IC50 values of 60, 95, 100 and 150 MUg/mL respectively. Likewise
      ABTS inhibition was most prominent for Nm.Sp, Nm.EtAc and Nm.Aq causing 78.26 +/-
      0.49, 67.67 +/- 0.73 and 63.58 +/- 0.45% inhibition respectively at 1 mg/mL.
      These results were further confirmed by qualitative screening using DPPH and ABTS
      staining. CONCLUSIONS: Our anticholinesterase and antioxidant results signify the
      N. micrantha as a potential source of natural bioactive compounds. Moreover
      isolation of natural bioactive compounds from this plant may lead to novel drug
      candidates against neurodegenerative disorders.

PMID- 29169350
TI  - "What say ye gout experts?" a content analysis of questions about gout posted on
      the social news website Reddit.
AB  - BACKGROUND: Social media is increasingly used by patients to source information
      for managing chronic disease. The aim of this study was to understand patient
      information needs about gout by a content analysis of questions posted on the
      social news website Reddit. METHODS: We analysed questions posted onto the 'Gout
      sufferers unite' subreddit site. Two reviewers coded questions into categories
      (inter-reviewer kappa 0.70), with discordant coding resolved by a third reviewer.
      Data were analysed by calculating the frequency of questions within the
      categories. Where relevant, categories were further separated into sub-categories
      to allow organisation and interpretation of the data. RESULTS: We analysed 359
      questions in 287 posts by 213 individuals. A wide range of questions arose. The
      single most common category related to uncertainty of diagnosis (22.3%
      questions), with questions about disease management common. Information-seeking
      about medications was generally cautious, with questions about side-effects, risk
      of flares after starting urate-lowering therapy, and decision to start urate
      lowering therapy. Community users experiencing flares posted questions about
      flare management, including medications, sometimes in real-time. Dietary
      management questions included the effectiveness of dietary changes as a
      management strategy, choice of alcoholic beverage, and weight loss strategies.
      Questions about serum urate levels were rare (2.8% questions). CONCLUSIONS:
      Questions about gout posted on the subreddit site most often related to
      uncertainty about symptoms and disease management strategies, with infrequent
      questions about serum urate testing, results or targets. These findings may
      inform development of strategies to address the information needs of people with
      gout.

PMID- 29169351
TI  - "We have been forced to move away from home": print news coverage of Canadians
      studying abroad at Caribbean offshore medical schools.
AB  - BACKGROUND: Canadian international medical graduates are Canadian-citizens who
      have graduated from a medical school outside of Canada or the United States. A
      growing number of Canadians enroll in medical school abroad, including at
      Caribbean offshore medical schools. Often, Canadians studying medicine abroad
      attempt to return to Canada for postgraduate residency training and ultimately to
      practice. METHODS: The authors conducted a qualitative media analysis to discern
      the dominant themes and ideologies that frame discussion of offshore medical
      schools, and the Canadian medical students they graduate, in the Canadian print
      news. We carried out structured searches on Canadian Newsstand Database for print
      media related to offshore medical schools. RESULTS: Canadian news articles used
      two frames to characterize offshore medical schools and the Canadian
      international medical graduates they train: (1) increased opportunity for medical
      education for Canadians; and (2) frustration returning to Canada to practice
      despite domestic physician shortages. CONCLUSION: Frames deployed by the Canadian
      print media to discuss Caribbean offshore medical schools and Canadians studying
      abroad define two problems: (1) highly qualified Canadians are unable to access
      medical school in Canada; and (2) some Canadian international medical graduates
      are unable to return to Canada to practice medicine. Caribbean offshore medical
      schools are identified as a solution to the first problem while playing a central
      role in creating the second problem. These frames do not acknowledge that medical
      school admissions are a primary means to control the make-up of the Canadian
      physician workforce and they do not address the nature of Canadian physician
      shortages.

PMID- 29169352
TI  - Arthroscopic internal drainage and cystectomy of popliteal cyst in knee
      osteoarthritis.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of
      arthroscopic knee cavity internal drainage and cyst cavity debridement operation
      of popliteal cyst in knee osteoarthritis patients. METHODS: From August 2007 to
      March 2013, 58 knee osteoarthritis patients with popliteal cyst were treated with
      arthroscopic knee cavity internal drainage through posteromedial portal and
      popliteal cyst cavity debridement through superior posteromedial portal. In all
      patients, preoperative magnetic resonance imaging (MRI) was performed to detect
      combined intra-articular pathology and the communication between popliteal cyst
      and knee cavity. Clinical efficacy was evaluated through VAS score and Lysholm
      score. RESULTS: All patients had neither recurrence of popliteal cyst nor
      complaints of pain, swelling, or functional impairment at average 24 months
      follow-up after surgery. Postoperatively, VAS score was decreased significantly
      and Lysholm score was raised significantly comparing preoperatively. CONCLUSION:
      Arthroscopic knee cavity internal drainage operation through posteromedial portal
      and popliteal cyst cavity debridement through superior posteromedial portal is an
      effective minimally invasive surgery method for the treatment of popliteal cyst
      without recurrence in knee osteoarthritis patients.

PMID- 29169353
TI  - Correction to: Long-term patient reported outcomes following radiation therapy
      for oropharyngeal cancer: cross-sectional assessment of a prospective symptom
      survey in patients >=65 years old.
AB  - In the original publication [1] the name of author Jeremy M. Aymard was spelled
      wrong. The original article was updated to rectify this error.

PMID- 29169354
TI  - Development of a novel Newcastle disease virus (NDV) neutralization test based on
      recombinant NDV expressing enhanced green fluorescent protein.
AB  - BACKGROUND: Newcastle disease is one of the most important infectious diseases of
      poultry, caused by Newcastle disease virus (NDV). This virus is distributed
      worldwide and it can cause severe economic losses in the poultry industry due to
      recurring outbreaks in vaccinated and unvaccinated flocks. Protection against NDV
      in chickens has been associated with development of humoral response. Although
      hemagglutination inhibition (HI) assay and ELISA do not corroborate the presence
      of neutralizing antibodies (nAbs); they are used to measure protection and immune
      response against NDV. METHODS: In this study, we established a system to recover
      a recombinant NDV (rLS1) from a cloned cDNA, which is able to accept exogenous
      genes in desired positions. An enhanced green fluorescent protein (eGFP) gene was
      engineered in the first position of the NDV genome and we generated a recombinant
      NDV carrying eGFP. This NDV- eGFP reporter virus was used to develop an eGFP
      based neutralization test (eGFP-NT), in which nAbs titers were expressed as the
      reciprocal of the highest dilution that expressed the eGFP. RESULTS: The eGFP-NT
      gave conclusive results in 24 h without using any additional staining procedure.
      A total of 57 serum samples were assayed by conventional neutralization (NT) and
      eGFP-NT. Additionally, HI and a commercial ELISA kit were evaluated with the same
      set of samples. Although HI (R 2 = 0.816) and ELISA (R 2 = 0.791) showed
      substantial correlation with conventional NT, eGFP-NT showed higher correlation
      (R 2 = 0.994), indicating that eGFP-NT is more accurate method to quantify nAbs.
      CONCLUSIONS: Overall, the neutralization test developed here is a simple, rapid
      and reliable method for quantitation of NDV specific nAbs. It is suitable for
      vaccine studies and diagnostics.

PMID- 29169355
TI  - A comparison of liquid and solid culture for determining relapse and durable cure
      in phase III TB trials for new regimens.
AB  - BACKGROUND: Tuberculosis kills more people than any other infectious disease, and
      new regimens are essential. The primary endpoint for confirmatory phase III
      trials for new regimens is a composite outcome that includes bacteriological
      treatment failure and relapse. Culture methodology is critical to the primary
      trial outcome. Patients in clinical trials can have positive cultures after
      treatment ends that may not necessarily indicate relapse, which was ascribed
      previously to laboratory cross-contamination or breakdown of old lesions.
      Lowenstein-Jensen (LJ) medium was the previous standard in clinical trials, but
      almost all current and future trials will use the Mycobacteria Growth Indicator
      Tube (MGIT) system due to its simplicity and consistency of use, which will
      affect phase III trial results. LJ was used for the definition of the primary
      endpoint in the REMoxTB trial, but every culture was also inoculated in parallel
      into the MGIT system. The data from this trial, therefore, provide a unique
      opportunity to investigate and compare the incidence of false 'isolated
      positives' in liquid and solid media and their potential impact on the primary
      efficacy results. METHODS: All post-treatment positive cultures were reviewed in
      the REMoxTB clinical trial. Logistic regression models were used to model the
      incidence of isolated positive cultures on MGIT and LJ. RESULTS: A total of
      12,209 sputum samples were available from 1652 patients; cultures were more often
      positive on MGIT than LJ. In 1322 patients with a favourable trial outcome, 126
      (9.5%) had cultures that were positive in MGIT compared to 34 (2.6%) patients
      with positive cultures on LJ. Among patients with a favourable outcome, the
      incidence of isolated positives on MGIT differed by study laboratory (p < 0.0001)
      with 21.9% of these coming from one laboratory investigating only 4.9% of
      patients. No other baseline factors predicted isolated positives on MGIT after
      adjusting for laboratory. There was evidence of clustering of isolated positive
      cultures in some patients even after adjusting for laboratory, p < 0.0001. The
      incidence of isolated positives on MGIT did not differ by treatment arm (p =
      0.845, unadjusted). Compared to negative MGIT cultures, positive MGIT cultures
      were more likely to be associated with higher grade TB symptoms reported within 7
      days either side of sputum collection in patients with an unfavourable primary
      outcome (p < 0.0001) but not in patients with a favourable outcome (p = 0.481).
      CONCLUSIONS: Laboratory cross-contamination was a likely cause of isolated
      positive MGIT cultures which were clustered in some laboratories. Certain
      patients had repeated positive MGIT cultures that did not meet the definition of
      a relapse. This pattern was too common to be explained by cross-contamination
      only, suggesting that host factors were also responsible. We conclude that MGIT
      can replace LJ in phase III TB trials, but there are implications for the
      definition of the primary outcome and patient management in trials in such
      settings. Most importantly, the methodologies differ in the incidence of isolated
      positives and in their capacity for capturing non-tuberculosis mycobacteria. It
      emphasises the importance of effective medical monitoring after treatment ends
      and consideration of clinical signs and symptoms for determining treatment
      failure and relapse.

PMID- 29169356
TI  - Aster koraiensis extract prevents diabetes-induced retinal vascular dysfunction
      in spontaneously diabetic Torii rats.
AB  - BACKGROUND: Aster koraiensis extract (AKE) is a standard dietary herbal
      supplement. The aim of this study is to investigate the inhibitory effects of AKE
      on diabetes-induced retinal vascular dysfunction in Spontaneously Diabetic Torii
      (SDT) rats. METHODS: AKE (50 and 100 mg/kg body weight/day) was administered for
      16 weeks. The effects of orally administered AKE on blood glucose levels, retinal
      vascular leakage, apoptosis, and accumulation of advanced glycation end products
      (AGEs) in the retina were evaluated. RESULTS: SDT rats exhibited hyperglycemia
      and retinal vascular leakage, and terminal deoxynucleotidyl transferase dUTP nick
      end labeling (TUNEL) staining was clearly detected apoptosis in the retinal
      microvasculature. Immunofluorescence staining revealed the accumulation of AGEs
      in the retinal vasculature of the SDT rats. However, oral administration of AKE
      for 16 weeks blocked diabetes-induced blood-retinal barrier (BRB) breakdown and
      the loss of occludin, which is an important tight junction protein. Apoptosis of
      retinal vascular cells and AGE accumulation were significantly inhibited after
      AKE treatment. CONCLUSION: These results indicate that, as a dietary herbal
      supplement, AKE may have beneficial effects on patients with diabetic
      retinopathy.

PMID- 29169357
TI  - In silico design of a Zika virus non-structural protein 5 aiming vaccine
      protection against zika and dengue in different human populations.
AB  - BACKGROUND: The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have
      important epidemiological impact in Brazil and other tropical regions of the
      world. Recently, it was shown that previous humoral immunity to DENV enhances
      ZIKV replication in vitro, which may lead to more severe forms of the disease.
      Thus, traditional approaches of vaccine development aiming to control viral
      infection through neutralizing antibodies may induce cross-reactive enhancing
      antibodies. In contrast, cellular immune response was shown to be capable of
      controlling DENV infection independently of antibodies. The aim of the present
      study was to design a flavivirus NS5 protein capable of inducing a cellular
      immune response against DENV and ZIKV. METHODS: A consensus sequence of ZIKV NS5
      protein was designed among isolates from various continents. Epitopes were
      predicted for the most prevalent alleles of class I and II HLA in the Brazilian
      population. Then, this epitopes were analyzed with regard to their conservation,
      population coverage and distribution along the whole antigen. RESULTS: Nineteen
      epitopes predicted to be more reactive (percentile rank <1) and 100% conserved
      among ZIKV and DENV serotypes were selected. The distribution of such epitopes
      along the protein was shown on a three-dimensional model and population coverage
      was calculated for different regions of the world. The designed protein was
      predicted to be stable and the distribution of selected epitopes was shown to be
      homogeneous along domains. The population coverage of selected epitopes was
      higher than 50% for most of tropical areas of the world. CONCLUSION: Such results
      indicate that the proposed antigen has the potential to induce protective
      cellular immune response to ZIKV and DENV in different human populations of the
      world.

PMID- 29169358
TI  - Risk factors for lymph node metastasis in early gastric cancer patients: Report
      from Eastern Europe country- Lithuania.
AB  - BACKGROUND: Current risk factors for lymph node metastasis in early gastric
      cancer have been primarily determined in Asian countries; however their
      applicability to Western nations is under discussion. The aim of our study was to
      identify risk factors associated with lymph node metastasis in Western cohort
      patients from the Eastern European country - Lithuania. METHODS: A total of 218
      patients who underwent open gastrectomy for early gastric cancer were included in
      this retrospective study. After histolopathological examination, risk factors for
      lymph node metastasis were evaluated. Overall survival was evaluated and factors
      associated with long-term outcomes were analyzed. RESULTS: Lymph node metastases
      were present in 19.7% of early gastric cancer cases. The rates were 5/99 (4.95%)
      for pT1a tumors and 38/119 (31.9%) for pT1b tumors. Submucosal tumor invasion,
      lymphovascular invasion, and high grade tumor differentiation were identified as
      independent risk factors for lymph node metastasis. Submucosal tumor invasion and
      lymphovascular invasion were also associated with worse 5-year survival results.
      CONCLUSION: Our study established submucosal tumor invasion, lymphovascular
      invasion, and high grade tumor differentiation as risk factors for lymph node
      metastasis.

PMID- 29169359
TI  - Evaluation of a practical expert defined approach to patient population
      segmentation: a case study in Singapore.
AB  - BACKGROUND: Segmenting the population into groups that are relatively homogeneous
      in healthcare characteristics or needs is crucial to facilitate integrated care
      and resource planning. We aimed to evaluate the feasibility of segmenting the
      population into discrete, non-overlapping groups using a practical expert and
      literature driven approach. We hypothesized that this approach is feasible
      utilizing the electronic health record (EHR) in SingHealth. METHODS: In addition
      to well-defined segments of "Mostly healthy", "Serious acute illness but curable"
      and "End of life" segments that are also present in the Ministry of Health
      Singapore framework, patients with chronic diseases were segmented into "Stable
      chronic disease", "Complex chronic diseases without frequent hospital
      admissions", and "Complex chronic diseases with frequent hospital admissions".
      Using the electronic health record (EHR), we applied this framework to all adult
      patients who had a healthcare encounter in the Singapore Health Services Regional
      Health System in 2012. ICD-9, 10 and polyclinic codes were used to define chronic
      diseases with a comprehensive look-back period of 5 years. Outcomes (hospital
      admissions, emergency attendances, specialist outpatient clinic attendances and
      mortality) were analyzed for years 2012 to 2015. RESULTS: Eight hundred twenty
      five thousand eight hundred seventy four patients were included in this study
      with the majority being healthy without chronic diseases. The most common chronic
      disease was hypertension. Patients with "complex chronic disease" with frequent
      hospital admissions segment represented 0.6% of the eligible population, but
      accounted for the highest hospital admissions (4.33 +/- 2.12 admissions; p <
      0.001) and emergency attendances (ED) (3.21 +/- 3.16 ED visits; p < 0.001) per
      patient, and a high mortality rate (16%). Patients with metastatic disease
      accounted for the highest specialist outpatient clinic attendances (27.48 +/-
      23.68 visits; p < 0.001) per patient despite their relatively shorter course of
      illness and high one-year mortality rate (33%). CONCLUSION: This practical
      segmentation framework can potentially distinguish among groups of patients, and
      highlighted the high disease burden of patients with chronic diseases. Further
      research to validate this approach of population segmentation is needed.

PMID- 29169360
TI  - Positioning pharmacists' roles in primary health care: a discourse analysis of
      the compensation plan in Alberta, Canada.
AB  - BACKGROUND: A comprehensive Compensation Plan for pharmacy services delivered by
      community pharmacists was implemented in Alberta, Canada in July 2012. Services
      covered by the Compensation Plan include care planning services, prescribing
      services such as adapting prescriptions, and administering a drug or publicly
      funded vaccine by injection. Understanding how the Compensation Plan was framed
      and communicated provides insight into the roles of pharmacists and the potential
      influence of language on the implementation of services covered by the
      Compensation Plan by Albertan pharmacists. The objective of this study is to
      examine the positioning of pharmacists' roles in documents used to communicate
      the Compensation Plan to Albertan pharmacists and other audiences. METHODS:
      Publicly available documents related to the Compensation Plan, such as news
      releases or reports, published between January 2012 and December 2015 were
      obtained from websites such as the Government of Alberta, Alberta Blue Cross, the
      Alberta College of Pharmacists, the Alberta Pharmacists' Association, and the
      Blueprint for Pharmacy. Searches of the Canadian Newsstand database and Google
      identified additional documents. Discourse analysis was performed using social
      positioning theory to explore how pharmacists' roles were constructed in
      communications about the Compensation Plan. RESULTS: In total, 65 publicly
      available documents were included in the analysis. The Compensation Plan was put
      forward as a framework for payment for professional services and formal
      legitimization of pharmacists' changing professional roles. The discourse
      associated with the Compensation Plan positioned pharmacists' roles as: (1)
      expanding to include services such as medication management for chronic diseases,
      (2) contributing to primary health care by providing access to services such as
      prescription renewals and immunizations, and (3) collaborating with other health
      care team members. Pharmacists' changing roles were positioned in alignment with
      the aims of primary health care. CONCLUSIONS: Social positioning theory provides
      a useful lens to examine the dynamic and evolving roles of pharmacists. This
      study provides insight into how communications regarding the Compensation Plan in
      Alberta, Canada positioned pharmacists' changing roles in the broader context of
      changes to primary health care delivery. Our findings may be useful for other
      jurisdictions considering implementation of remunerated clinical services
      provided by pharmacists.

PMID- 29169361
TI  - Differentiation of human adipose-derived stem cells into cardiomyocyte-like cells
      in fibrin scaffold by a histone deacetylase inhibitor.
AB  - BACKGROUND: Human adipose-derived stem cells (hADSCs) are capable of
      differentiating into many cells such as cardiac cells. Different types of
      inducers are used for cardiac cell differentiation, but this question still
      remains to be investigated, which one is the best. The aim of this paper was to
      investigate the effect of combination of fibrin scaffold and trichostatin A
      (TSA), for differentiation of hADSCs into cardiomyocyte-like cells. METHODS:
      After approval of characteristics of hADSCs and fibrin scaffold, hADSCs were
      cultured in fibrin scaffold with 10 uM TSA for 72 h and kept in standard
      conditions for 4 weeks. QRT-PCR and immunostaining assay were performed for
      evaluating the expression pattern of special cardiac genes and proteins. RESULTS:
      In particular, our study showed that fibrin scaffold alongside TSA enhanced
      expression of the selected genes and proteins. CONCLUSIONS: We concluded that the
      TSA alone or with fibrin scaffold can lead to the generation of cardiac like
      cells in a short period of time.

PMID- 29169362
TI  - Influence of enhanced recovery after surgery programs on laparoscopy-assisted
      gastrectomy for gastric cancer: a systematic review and meta-analysis of
      randomized control trials.
AB  - BACKGROUND: This meta-analysis is aimed to evaluate the feasibility and safety of
      enhanced recovery after surgery (ERAS) programs in gastric cancer patients
      undergoing laparoscopy-assisted gastrectomy (LAG). METHODS: We performed a meta
      analysis of randomized control trials involving either enhanced recovery after
      surgery (ERAS)/fast track surgery (FTS) for patients underwent LAG. EMBASE,
      Pubmed, Web of science, and Cochrane Library were searched. Primary outcomes
      included the length of postoperative hospital stay, cost of hospitalization,
      postoperative complications, and readmission rate. RESULTS: Five randomized
      control trials were eligible for analysis. There were 159 cases in FTS group and
      156 cases in conventional care group. Compared with conventional care group, FTS
      group relates to shorter postoperative hospital stay (WMD - 2.16; 95% CI - 3.05
      to - 1.26, P < 0.00001), less cost of hospitalization (WMD - 4.72; 95% CI - 6.88
      to - 2.55, P < 0.00001), shorter time to first flatus (WMD - 9.72; 95% CI - 13.75
      to - 5.81, P < 0.00001), lower level of C-reaction protein on postoperative days
      3 or 4 (WMD - 19.66; 95% CI - 28.98 to - 10.34, P < 0.00001), higher level of
      albumin on postoperative day 4 (WMD 3.45; 95% CI 2.01 to 4.89, P < 0.00001), and
      postoperative day 7 (WMD 5.63; 95% CI 1.01 to 10.24, P = 0.02). Regarding
      postoperative complications, no significant differences were observed between FTS
      group and conventional care group (OR 0.63, 95% CI 0.37 to 1.09, P = 0.10). The
      readmission rate of FTS group was comparable to conventional care group (WMD
      3.14; 95% CI 0.12 to 81.35, P = 0.49). CONCLUSIONS: Among patients undergoing
      LAG, FTS is associated with shorter postoperative hospital stay, rapid
      postoperative recovery, and decreased cost without increasing complications or
      readmission rate. The combined effects of the two methods could further
      accelerate clinical recovery of gastric cancer patients.

PMID- 29169363
TI  - Impact of connective tissue disease on the surgical outcomes of aortic dissection
      in patients with cystic medial necrosis.
AB  - BACKGROUND: A retrospective analysis was performed to determine the impact of
      genetically diagnosed connective tissue disease (CTD) on the early and late
      outcomes of surgical treatment for aortic dissection in patients having aortic
      pathology associated with cystic medial necrosis (CMN). METHODS: Between 2003 and
      2013, a total of 43 patients (37 +/- 12.8 years old, 23 men, 20 women) who had
      undergone surgery for aortic dissection associated with CMN in the aortic wall
      underwent genetic examinations. Subsequently, there were 30 patients with CTD
      (CTD group) and 13 without CTD (non-CTD group). RESULTS: There were no early or
      late deaths (the follow-up rate was 100% for 57.1 +/- 43.0 months). The median
      age was significantly lower in the CTD group (p = 0.030). The rate of elastic
      fiber loss was significantly higher in the CTD group (p = 0.014). In the long
      term follow-up, there were no significant differences in the incidences of re
      dissection (p = 0.332). However, re-operations were required more frequently in
      the CTD group (p = 0.037). CONCLUSIONS: In patients with CTD as well as CMN, the
      onset of aortic dissection tends to be earlier, which would result in higher
      rates of re-operation, compared with the non-CTD group. Closer and stricter
      follow-up with medication and adequate surgical treatments with appropriate
      timing are mandatory for such high-risk patients.

PMID- 29169364
TI  - Policymakers' experience of a capacity-building intervention designed to increase
      their use of research: a realist process evaluation.
AB  - BACKGROUND: An intervention's success depends on how participants interact with
      it in local settings. Process evaluation examines these interactions, indicating
      why an intervention was or was not effective, and how it (and similar
      interventions) can be improved for better contextual fit. This is particularly
      important for innovative trials like Supporting Policy In health with Research:
      an Intervention Trial (SPIRIT), where causal mechanisms are poorly understood.
      SPIRIT was testing a multi-component intervention designed to increase the
      capacity of health policymakers to use research. METHODS: Our mixed-methods
      process evaluation sought to explain variation in observed process effects across
      the six agencies that participated in SPIRIT. Data collection included
      observations of intervention workshops (n = 59), purposively sampled interviews
      (n = 76) and participant feedback forms (n = 553). Using a realist approach, data
      was coded for context-mechanism-process effect configurations (retroductive
      analysis) by two authors. RESULTS: Intervention workshops were very well
      received. There was greater variation of views regarding other aspects of SPIRIT
      such as data collection, communication and the intervention's overall value. We
      identified nine inter-related mechanisms that were crucial for engaging
      participants in these policy settings: (1) Accepting the premise (agreeing with
      the study's assumptions); (2) Self-determination (participative choice); (3) The
      Value Proposition (seeing potential gain); (4) 'Getting good stuff' (identifying
      useful ideas, resources or connections); (5) Self-efficacy (believing 'we can do
      this!'); (6) Respect (feeling that SPIRIT understands and values one's work); (7)
      Confidence (believing in the study's integrity and validity); (8) Persuasive
      leadership (authentic and compelling advocacy from leaders); and (9) Strategic
      insider facilitation (local translation and mediation). These findings were used
      to develop tentative explanatory propositions and to revise the programme theory.
      CONCLUSION: This paper describes how SPIRIT functioned in six policy agencies,
      including why strategies that worked well in one site were less effective in
      others. Findings indicate a complex interaction between participants' perception
      of the intervention, shifting contextual factors, and the form that the
      intervention took in each site. Our propositions provide transferable lessons
      about contextualised areas of strength and weakness that may be useful in the
      development and implementation of similar studies.

PMID- 29169365
TI  - Physician perspectives on the burden and management of asthma in six countries:
      The Global Asthma Physician Survey (GAPS).
AB  - BACKGROUND: Despite recognition of asthma as a growing global issue and
      development of global guidelines, asthma treatment practices vary between
      countries. Several studies have reported patients' perspectives on asthma
      control. This study presents physicians' perspectives and strategies for asthma
      management. METHODS: Physicians seeing >=4 adult patients with asthma per month
      in Australia, Canada, China, France, Germany, and Japan were surveyed (N=1809;
      ~300 per country). A standardised questionnaire was developed for this study and
      administered by telephone, online or face-to-face. Statistics were weighted to
      account for the sampling scheme. RESULTS: Physicians estimated that 71% of their
      adult patients received maintenance medication, with adherence monitored by 76
      97% of physicians. Perceived major barriers to patient adherence included:
      patients taking treatment as needed; acceptance of symptoms; and patients not
      perceiving treatment benefits. Written action plans (37%) and technology (15%)
      were seldom employed by physicians to aid patients' asthma management. Physicians
      rarely (10%) used validated patient-reported questionnaires to monitor asthma
      control, instead monitoring selected symptoms, exacerbations, and/or lung
      function measurements. Awareness of single maintenance and reliever therapy
      (SMART/MART) varied among countries (56-100%); although most physicians (72%) had
      prescribed SMART/MART, the majority (91%) co-prescribed a short-acting
      bronchodilator at least some of the time. CONCLUSIONS: These results show that
      physicians generally do not employ standardised tools to monitor asthma control
      or to manage its treatment and that despite high awareness of SMART/MART, the
      strategy appears to be commonly misapplied. Better education for patients and
      physicians is required to improve asthma management and resulting patient
      outcomes.

PMID- 29169366
TI  - A case report of pulmonary tritrichomonosis in a pig.
AB  - BACKGROUND: Tritrichomonads like porcine Tritrichomonas foetus (previously named
      Tritrichomonas suis), can commensally live in nasal cavity of pigs, but it is
      rare to cause pulmonary tritrichomonosis. CASE PRESENTATION: A 40-day-old piglet
      was presented for persistent labor breathing and diagnosed with parasite
      infections in the lung by analysis of bronchoalveolar lavage (BAL) under
      microscope. By taking advantage of next-generation sequencing approach, we found
      9611 homologous tags belonging to 50 annotated genes of tritrichomonads by
      analysis of mRNA of the bronchoalveolar lavage with the parasite infection.
      Furthermore, RT-PCR and DNA sequencing analysis confirmed the presence of the
      tritrichomonad. FINDINGS: Here, we report a case of pulmonary tritrichomonosis in
      a pig. By taking advantage of next-generation sequencing approach, we found 9611
      homologous tags belonging to 50 annotated genes of tritrichomonads by analysis of
      mRNA of the bronchoalveolar lavage with the parasite infections. Furthermore, RT
      PCR and DNA sequencing analysis confirmed the presence of the tritrichomonad.
      CONCLUSION: Our results demonstrate that tritrichomonads like porcine
      Tritrichomonas foetus can cause lung infections of pigs and reveal that next
      generation sequencing is potential to identify rare diseases like pulmonary
      tritrichomonosis in clinical.

PMID- 29169367
TI  - Image-based quantitative analysis of tear film lipid layer thickness for
      meibomian gland evaluation.
AB  - BACKGROUND: Dry eye syndrome is one of the most common ocular diseases, and
      meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye
      syndrome. When the tear film lipid layer becomes thin due to obstructive or
      hyposecretory meibomian gland dysfunction, the excessive evaporation of the
      aqueous layer can occur, and this causes evaporative dry eye syndrome. Thus,
      measuring the lipid layer thickness (LLT) is essential for accurate diagnosis and
      proper treatment of evaporative dry eye syndrome. METHODS: We used a white LED
      panel with a slit lamp microscope to obtain videos of the lipid layer
      interference patterns on the cornea. To quantitatively analyze the LLT from
      interference colors, we developed a novel algorithm that can automatically
      perform the following processes on an image frame: determining the radius of the
      iris, locating the center of the pupil, defining region of interest (ROI),
      tracking the ROI, compensating for the color of iris and illumination, and
      producing comprehensive analysis output. A group of dry eye syndrome patients
      with hyposecretory MGD, dry eye syndrome without MGD, hypersecretory MGD, and
      healthy volunteers were recruited. Their LLTs were analyzed and statistical
      information-mean and standard deviation, the relative frequency of LLT at each
      time point, and graphical LLT visualization-were produced. RESULTS: Using our
      algorithm, we processed the lipid layer interference pattern and automatically
      analyzed the LLT distribution of images from patients. The LLT of hyposecretory
      MGD was thinner (45.2 +/- 11.6 nm) than that of dry eye syndrome without MGD
      (69.0 +/- 9.4 nm) and healthy volunteers (68.3 +/- 13.7 nm) while the LLT of
      hypersecretory MGD was thicker (93.5 +/- 12.6 nm) than that of dry eye syndrome
      without MGD. Patients' LLTs were statistically analyzed over time, visualized
      with 3D surface plots, and displayed using 3D scatter plots of image pixel data
      for comprehensive assessment. CONCLUSIONS: We developed an image-based algorithm
      for quantitative measurement as well as statistical analysis of the LLT despite
      fluctuation and eye movement. This pilot study demonstrates that the quantitative
      LLT analysis of patients is consistent with the functions of meibomian glands
      clinically evaluated by an ophthalmologist. This approach is a significant step
      forward in developing a fully automated instrument for evaluating dry eye
      syndrome and for providing proper guidance of treatment.

PMID- 29169368
TI  - Inactive lifestyles and sedentary behavior in persons with chronic aneurysmal
      subarachnoid hemorrhage: evidence from accelerometer-based activity monitoring.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (a-SAH) is a potential life
      threatening stroke. Because survivors may be at increased risk for inactive and
      sedentary lifestyles, this study evaluates physical activity (PA) and sedentary
      behavior (SB) in the chronic phase after a-SAH. METHODS: PA and SB were
      objectively measured at six months post a-SAH with an accelerometer-based
      activity monitor, with the aim to cover three consecutive weekdays. Total time
      spent in PA (comprising walking, cycling, running and non-cyclic movement) and SB
      (comprising sitting and lying) was determined. Also, in-depth analyses were
      performed to determine the accumulation and distribution of PA and SB throughout
      the day. Binary time series were created to determine the mean bout length and
      the fragmentation index. Measures of PA and SB in persons with a-SAH were
      compared to those in sex- and age-matched healthy controls. RESULTS: The 51
      participants comprised 33 persons with a-SAH and 18 controls. None of the
      participants had signs of paresis or spasticity. Persons with a-SAH spent 105
      min/24 h being physically active, which was 35 min/24 h less than healthy
      controls (p = 0.005). For PA, compared with healthy controls, the mean bout
      length was shorter in those with a-SAH (12.0 vs. 13.5 s, p = 0.006) and the
      fragmentation index was higher (0.053 vs. 0.041, p < 0.001). Total sedentary time
      during waking hours showed no significant difference between groups (514 min vs.
      474 min, p = 0.291). For SB, the mean bout length was longer in persons with a
      SAH (122.3 vs. 80.5 s, p = 0.024), whereas there was no difference in
      fragmentation index between groups (0.0032 vs 0.0036, p = 0.396). CONCLUSIONS:
      Persons with a-SAH are less physically active, they break PA time into shorter
      periods, and SB periods last longer compared to healthy controls. Since inactive
      lifestyles and prolonged uninterrupted periods of SB are independent risk factors
      for poor cardiovascular health, interventions seem necessary and should target
      both PA and SB. STUDY REGISTRATION: Dutch registry number: NTR 2085.

PMID- 29169369
TI  - In vivo screening and evaluation of four herbs against MRSA infections.
AB  - BACKGROUND: Recently, we reported high in vitro antibacterial efficacy of Althaea
      officinalis, Ziziphus jujuba, Cordia latifolia and Thymus vulgaris out of a total
      21 plants against wide range of bacteria including MRSA. This study was
      therefore, designed to confirm efficacy of these four herbs against MRSA in an
      animal model. METHODS: A pilot study was conducted to establish the dose of S.
      aureus (KY698020) required to induce clinical infection. Afterword, in main
      trial, efficacy of aforementioned plant extracts on the course of sore throat was
      checked by evaluating general health, gross lesion score, bacterial load and
      hematology in mice. RESULTS: Pilot study revealed that 40 MUl dose of 107 CFU/ml
      could induce infection which persist upto 08 days post infection. Mice treated
      with T. vulgaris and Z. jujuba showed reduction in gross lesion score of both
      heart and lungs. Treatment with only some plants could significantly decrease
      bacterial load of throat (T. vulgaris) heart, blood and joint (C. latifolia, and
      T. vulagris). Hematological indicators confirmed in vivo control of MRSA
      infection in all treatment groups except A. officinalis. CONCLUSION: This is
      first report confirming in vivo anti-MRSA potential of C. latifolia and T.
      vulgaris and highlight the need to explore bioactive constituents of these
      plants. Moreover, previously reported in vitro antibacterial efficiency of A.
      officinalis could not be validated in current study.

PMID- 29169370
TI  - Cisplatin triggers cancer stem cell enrichment in platinum-resistant cells
      through NF-kappaB-TNFalpha-PIK3CA loop.
AB  - BACKGROUND: Parallel to complex alteration in molecular and cellular events,
      enrichment of cancer stem cells (CSC) contributes significantly in deliberation
      and maintenance of cisplatin resistance. Cisplatin mediated CSC enrichment is
      well established in various cancers, yet the underlying mechanism is largely
      unknown. Cisplatin also promotes transcriptional upregulation of PIK3CA, hence
      activating PI3K/AKT signaling in resistant cells. However, such cisplatin-induced
      transcriptional regulators of PIK3CA and their impact on cancer stem cell
      population in resistant cells are largely unknown. METHODS: DNA-binding protein
      pulldown using PIK3CA promoter as bait followed by nLCMS was used to identify,
      cisplatin-induced potential transcriptional regulators of PIK3CA promoter. PIK3CA
      promoter activity was estimated by luciferase based reporter assay. ChIP was used
      to assess interaction of NF-kappaB with PIK3CA promoter. CSC-enriched side
      population was sorted using DCV-dye exclusion methods. All the gene expression
      levels were assessed using qPCR. RESULTS: Using a transcription factor pull-down
      assay with PIK3CA promoter, we identified NF-kappaB as a prime regulator, which
      escalates both TNFalpha and PIK3CA expression only in CSC enriched side
      population (SP) but not in non side-population (NSP) in platinum resistant
      ovarian cancer cells upon cisplatin treatment. This SP-specific NF-kappaB
      TNFalpha-PIK3CA bi-modal loop, on one hand, maintains persistent activation of NF
      kappaB through TNFalpha- NF-kappaB autocrine loop, while NF-kappaB-PIK3CA loop
      nurture CSC population under cisplatin treatment. Activation of PI3K/AKT
      signalling drives SP's into an undifferentiated, anti-apoptotic stage through
      upregulating P21, P27,cFLIP expression. Contrarily, lack of active NF-kappaB
      TNFalpha-PIK3CA loop makes NSPs vulnerable towards cisplatin and undergoes
      apoptosis. Altogether, cisplatin enriches cancer stem cells properties in SP
      fraction, which is evident from increased levels of pluripotency gene
      OCT4/SOX2/NANOG expression. Disruption of PIK3CA-NF-kappaB loop by Wortamannin
      reduces SP fraction by 1.4-1.6 fold in control and treated cells. CONCLUSION:
      Together, our study signifies an active role of NF-kappaB-TNFalpha-PIK3CA bi
      modal loop in cisplatin-mediated promotion and maintenance of CSC-like population
      in platinum-resistant cells.

PMID- 29169371
TI  - Computational biologists: moving to the driver's seat.
AB  - The recent shift of computational biologists from bioinformatics service
      providers to leaders of cutting-edge programs highlights the accompanying
      cultural and conceptual changes that should be implemented by funding bodies and
      academic institutions.

PMID- 29169372
TI  - Association between diet and gallstones of cholesterol and pigment among patients
      with cholecystectomy: a case-control study in Korea.
AB  - BACKGROUND: The prevalence of cholesterol gallstones is high in Western
      populations, while pigment gallstones are common in Asian populations. Dietary
      factors are suggested to be associated with gallstone risk, but their
      relationship with gallstone type has not been evaluated. This study investigated
      the association between diet and risk of cholesterol gallstone or pigment
      gallstone in a Korean population whose dietary pattern and type of gallstone were
      changed during the last 30 years. METHODS: Patients with cholesterol (n = 40) and
      pigment (n = 59) gallstones were recruited after laparoscopic cholecystectomy and
      were compared with those of age- and sex-matched controls without gallstones (n =
      99). Dietary intakes were assessed by trained dietitians using a semi
      quantitative food frequency questionnaire. Multinomial logistic regression
      analysis was performed to calculate odds ratios and 95% confidence intervals to
      examine the associations between diet and risk for type of gallstones adjusted by
      potential confounders. RESULTS: Patients with cholesterol gallstone consumed more
      lipid, animal lipid, beef, pork, and fried food than those with pigment
      gallstones and control, while patients with pigment gallstone consumed more
      carbohydrate and noodles than patients with cholesterol gallstone and control. In
      multinomial logistic regression analysis using control as reference group,
      dietary pattern with high consumption of beef, pork, and fried food was
      associated with risk of cholesterol gallstones, while there was no association
      between the risk of pigment gallstone and dietary pattern. In addition, control
      consumed more alcohol than patients with cholesterol and pigment gallstones.
      CONCLUSIONS: The present study suggested consumption of fat from meat and fried
      foods increased the risk of cholesterol gallstone, and intake of carbohydrate
      from noodles increased the risk of pigment gallstone.

PMID- 29169373
TI  - The Treatment In Morning versus Evening (TIME) study: analysis of recruitment,
      follow-up and retention rates post-recruitment.
AB  - BACKGROUND: The use of information technology (IT) is now the preferred method of
      capturing and storing clinical research data. The Treatment In Morning versus
      Evening (TIME) study predominantly uses electronic data capture and IT to compare
      morning dosing of hypertensive medication against evening dosing. Registration,
      consent, participant demographics and follow-up data are all captured via the
      study website. The aim of this article is to assess the success of the TIME
      methodology compared with similar studies. METHODS: To assess the TIME study,
      published literature on similar clinical trials was reviewed and compared against
      TIME recruitment, follow-up and email interaction data. RESULTS: The TIME website
      registered 31,695 individuals, 21,116 of whom were randomised. Recruitment cost
      per randomised participant varied by strategy: L17.40 by GP practice, L3.08 by UK
      Biobank and L58.82 for GoShare. Twelve-month follow-up retention rates were 96%.
      A total of 1089 participants have withdrawn from their assigned time of dosing,
      2% of whom have declined follow-up by record linkage or further contact. When the
      TIME data are compared with similar study data, study recruitment is very
      successful. However, TIME suffers difficulties with participant follow-up and
      withdrawal rates similar to those of conventional studies. CONCLUSIONS: The TIME
      study has been successful in recruitment. Follow-up, retention rates and
      withdrawal rates are all acceptable, but ongoing work is required to ensure
      participants remain engaged with the study. Various recruitment strategies are
      necessary, and all viable options should be encouraged to maintain participant
      engagement throughout the life of studies using IT.

PMID- 29169374
TI  - ID1 promotes hepatocellular carcinoma proliferation and confers chemoresistance
      to oxaliplatin by activating pentose phosphate pathway.
AB  - BACKGROUND: Drug resistance is one of the major concerns in the treatment of
      hepatocellular carcinoma (HCC). The aim of the present study was to determine
      whether aberrant high expression of the inhibitor of differentiation 1(ID1)
      confers oxaliplatin-resistance to HCC by activating the pentose phosphate pathway
      (PPP). METHODS: Aberrant high expression of ID1 was detected in two oxaliplatin
      resistant cell lines MHCC97H-OXA(97H-OXA) and Hep3B-OXA(3B-OXA). The lentiviral
      shRNA or control shRNA was introduced into the two oxaliplatin-resistant cell
      lines. The effects of ID1 on cell proliferation, apoptosis and chemoresistance
      were evaluated in vitro and vivo. The molecular signaling mechanism underlying
      the induction of HCC proliferation and oxaliplatin resistance by ID1 was
      explored. The prognostic value of ID1/G6PD signaling in HCC patients was assessed
      using the Cancer Genome Atlas (TCGA) database. RESULTS: ID1 was upregulated in
      oxaliplaitin-resistant HCC cells and promoted HCC cell proliferation and
      oxaliplatin resistance. Silencing ID1 expression in oxaliplaitin-resistant HCC
      cell lines inhibited cell proliferation and sensitized oxaliplaitin-resistant
      cells to death. ID1 knockdown significantly decreased the expression of glucose-6
      phosphate dehydrogenase (G6PD), a key enzyme of the PPP. Silencing ID1 expression
      blocked the activation of G6PD, decreased the production of PPP NADPH, and
      augmented reactive oxygen and species (ROS), thus inducing cell apoptosis. Study
      of the molecular mechanism showed that ID1 induced G6PD promoter transcription
      and activated PPP through Wnt/beta-catenin/c-MYC signaling. In addition, ID1/G6PD
      signaling predicted unfavorable prognosis of HCC patients on the basis of TCGA.
      CONCLUSIONS: Our study provided the first evidence that ID1 conferred oxaliplatin
      resistance in HCC by activating the PPP. This newly defined pathway may have
      important implications in the research and development of new more effective anti
      cancer drugs.

PMID- 29169376
TI  - The mediating factors in the relationship between lower urinary tract symptoms
      and health-related quality of life.
AB  - OBJECTIVES: An earlier study found that mental health partially mediates the
      relationship between lower urinary tract symptoms (LUTS) severity and health
      related quality of life (HRQOL). In other words, LUTS adversely affects mental
      health, which in turn adversely affects HRQOL. A major limitation of the previous
      study was its cross-sectional design. The aim of this study is to evaluate
      whether changes in mental health mediated the association between changes in the
      severity of LUTS and changes in HRQOL over 24 months by using Baron and Kenny's
      regression procedure and Preacher and Hayes's bootstrapping method. RESULTS: We
      found that changes in mental health were a mediator in the relationship between
      the change of LUTS severity and the change of LUTS-specific HRQOL. Changes in
      LUTS severity lead to changes in mental health, which in turn affects the change
      of LUTS-specific HRQOL. It was observed however that changes in mental health did
      not mediate the relationship between the change of LUTS severity and the change
      of the physical aspects of generic HRQOL. These findings suggest that in order to
      optimize LUTS-specific HRQOL, both LUTS severity and mental health may need to be
      addressed concurrently.

PMID- 29169375
TI  - Synaptic configuration of quadrivalents and their association with the XY
      bivalent in spermatocytes of Robertsonian heterozygotes of Mus domesticus.
AB  - BACKGROUND: The nuclear architecture of meiotic prophase spermatocytes is based
      on higher-order patterns of spatial associations among chromosomal domains and
      consequently is prone to modification by chromosomal rearrangements. We have
      shown that nuclear architecture is modified in spermatocytes of Robertsonian (Rb)
      homozygotes of Mus domesticus. In this study we analyse the synaptic
      configuration of the quadrivalents formed in the meiotic prophase of
      spermatocytes of mice double heterozygotes for the dependent Rb chromosomes: Rbs
      11.16 and 16.17. RESULTS: Electron microscope spreads of 60 pachytene
      spermatocytes from four animals of Mus domesticus 2n = 38 were studied and their
      respective quadrivalents analysed in detail. Normal synaptonemal complex was
      found between arms 16 of the Rb metacentric chromosomes, telocentrics 11 and 17
      and homologous arms of the Rb metacentric chromosomes. About 43% of the
      quadrivalents formed a synaptonemal complex between the heterologous short arms
      of chromosomes 11 and 17. This synaptonemal complex is bound to the nuclear
      envelope through a fourth synapsed telomere, thus dragging the entire
      quadrivalent to the nuclear envelope. About 57% of quadrivalents showed
      unsynapsed single axes in the short arms of the telocentric chromosomes. About
      90% of these unsynapsed quadrivalents also showed a telomere-to-telomere
      association between one of the single axes of the telocentric chromosome 11 or 17
      and the X chromosome single axis, which was otherwise normally paired with the Y
      chromosome. Nucleolar material was associated with two bivalents and with the
      quadrivalent. CONCLUSIONS: The spermatocytes of heterozygotes for dependent Rb
      chromosomes formed a quadrivalent where four chromosomes are synapsed together
      and bound to the nuclear envelope through four telomeres. The nuclear
      configuration is determined by the fourth shortest telomere, which drags the
      centromere regions and heterochromatin of all the chromosomes towards the nuclear
      envelope, favouring the reiterated encounter and eventual rearrangement between
      the heterologous chromosomes. The unsynapsed regions of quadrivalents are
      frequently bound to the single axis of the X chromosome, possibly perturbing
      chromatin condensation and gene expression.

PMID- 29169377
TI  - First detection of Wolbachia-infected Culicoides (Diptera: Ceratopogonidae) in
      Europe: Wolbachia and Cardinium infection across Culicoides communities revealed
      in Spain.
AB  - BACKGROUND: Biting midges of the genus Culicoides (Diptera: Ceratopogonidae)
      transmit pathogens that cause important diseases. No effective technique has been
      found to properly control either Culicoides spp. abundance or their likelihood to
      transmit pathogens. Endosymbionts, particularly Wolbachia, represent powerful
      alternatives to control arthropods of health interest. In arthropods, Wolbachia
      can reduce vector fitness and vector's pathogen transmission capacity, thus being
      a potential target for population reduction and replacement strategies. RESULTS:
      The presence of Wolbachia and Cardinium endosymbionts was screened in Spanish
      Culicoides spp. populations at livestock premises and natural habitats. The first
      detection of Wolbachia-infected Culicoides spp. in Europe is reported. The
      putative Palaearctic vectors for bluetongue and Schmallenberg diseases, C.
      imicola, C. obsoletus (s.s.) and C. pulicaris (s.l.), were infected with
      Wolbachia. Four genetic clusters of closely-related Wolbachia strains from A and
      B supergroups were detected infecting Culicoides. Cardinium strain of the C-group
      was detected in C. obsoletus (s.l.). Both endosymbionts, Wolbachia and Cardinium,
      were detected in Culicoides species of minor epidemiological relevance as well.
      Higher prevalence of Wolbachia infection was detected in natural habitats, while
      livestock premises lead to higher prevalence of Cardinium. Significant
      differences in the prevalence of Wolbachia, but not Cardinium, were also detected
      between some Culicoides species and between locations. CONCLUSIONS: The presence
      of Wolbachia and Cardinium endosymbionts in Culicoides is expected to trigger new
      research towards the control of Culicoides-transmitted diseases. The results of
      the present study could have an impact beyond the Culicoides arena because
      successful Wolbachia transfection is possible even across genus and species
      barriers.

PMID- 29169378
TI  - Network methods to support user involvement in qualitative data analyses: an
      introduction to Participatory Theme Elicitation.
AB  - BACKGROUND: While Patient and Public Involvement (PPI) is encouraged throughout
      the research process, engagement is typically limited to intervention design and
      post-analysis stages. There are few approaches to participatory data analyses
      within complex health interventions. METHODS: Using qualitative data from a
      feasibility randomised controlled trial (RCT), this proof-of-concept study tests
      the value of a new approach to participatory data analysis called Participatory
      Theme Elicitation (PTE). Forty excerpts were given to eight members of a youth
      advisory PPI panel to sort into piles based on their perception of related
      thematic content. Using algorithms to detect communities in networks, excerpts
      were then assigned to a thematic cluster that combined the panel members'
      perspectives. Network analysis techniques were also used to identify key excerpts
      in each grouping that were then further explored qualitatively. RESULTS: While
      PTE analysis was, for the most part, consistent with the researcher-led analysis,
      young people also identified new emerging thematic content. CONCLUSIONS: PTE
      appears promising for encouraging user led identification of themes arising from
      qualitative data collected during complex interventions. Further work is required
      to validate and extend this method. TRIAL REGISTRATION: ClinicalTrials.gov, ID:
      NCT02455986 . Retrospectively Registered on 21 May 2015.

PMID- 29169379
TI  - Exponential distribution of total depressive symptom scores in relation to
      exponential latent trait and item threshold distributions: a simulation study.
AB  - OBJECTIVES: Total depressive symptom scores in the general population have been
      reported to follow an exponential distribution except at the lowest end of the
      range of scores. To verify the hypothesis that total depressive symptom scores
      follow the distribution of the latent trait, we performed a simulation study of
      depressive symptom scoring modeled after the Revised Clinical Interview Schedule
      (CIS-R). To simulate the scoring of ordinal scale items in CIS-R, two sets of
      random numbers were generated, one expressing the degree of the latent trait of
      depressive symptoms and another expressing the threshold for each item. Random
      latent trait numbers greater than those of item thresholds indicated the presence
      of specific symptoms. RESULTS: When exponential distribution was set to the
      latent trait's random numbers and each item's threshold had a certain degree of
      standard deviation, simulated total depressive symptom scores showed a linear
      pattern except at the lowest end of scores with a log-normal scale. Our results
      suggest that total depressive symptom scores follow the distribution of the
      latent trait of depressive symptoms due to the property of ordinal scales, which
      is characterized by individual differences in the threshold of each item.

PMID- 29169380
TI  - Correction to: Routinely detected indicators in plasma have a predictive effect
      on the identification of HIV-infected patients with non-tuberculous mycobacterial
      and tuberculous infections.
AB  - CORRECTION: After publication of this article [1] it came to our attention that
      the affiliation of Jun Chen and Hong-zhou Lu were incorrectly shown.Jun Chen's
      affiliation should have been given as Department of Infectious Diseases, Shanghai
      Public Health Clinical Center, Fudan University, Shanghai, China.Hong-zhou Lu
      should have been given as Department of Infectious Diseases, Shanghai Public
      Health Clinical Center, Fudan University, Shanghai, China. Huashan Hospital
      affiliated to Fudan University, Shanghai, China. Medical College of Fudan
      University, Shanghai, China.The original article has been updated to reflect this
      change.

PMID- 29169381
TI  - Surgical resection of advanced non-small cell lung cancer after a response to
      EGFR-TKI: presentation of two cases and a literature review.
AB  - BACKGROUND: The usefulness of residual tumor resection after epidermal growth
      factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment remains unclear.
      We describe two patients who underwent residual tumor resection after responding
      to EGFR-TKIs for advanced non-small cell lung cancer (NSCLC) harboring EGFR gene
      mutations, along with a review of the literature. CASE PRESENTATION: The patient
      in Case 1 was a 72-year-old female non-smoker who was initially diagnosed with
      T2aN2M0, stage IIIA adenocarcinoma harboring an EGFR exon 21 L858R mutation.
      After 8 months of gefitinib therapy, a marked radiologic response was noted, and
      right upper lobectomy with systemic lymph node dissection was performed. The
      patient developed brain metastasis despite continuous gefitinib therapy. The
      patient in Case 2 was a 68-year-old female non-smoker who was initially diagnosed
      with T3N2M0, stage IIIA adenocarcinoma and an extensive pulmonary
      thromboembolism. After 3 months of therapy with afatinib and anticoagulants, a
      marked radiologic response and symptom relief were achieved. We then performed
      right bilobectomy with systemic lymph node dissection. She developed bone
      metastasis despite postoperative afatinib therapy. CONCLUSION: The timing and
      validity of salvage surgery for residual lesions remain unclear when TKIs are
      offered as first-line therapy to patients with advanced NSCLC. In our two cases,
      surgery was performed without any complications. Surgical resection of the
      residual tumor might contribute to good local control. The accumulation of more
      clinical data is needed to further investigate the role of surgery in patients
      with advanced NSCLC harboring EGFR gene mutations.

PMID- 29169382
TI  - Confirmed Ceylon krait (Bungarus ceylonicus) envenoming in Sri Lanka resulting in
      neuromuscular paralysis: a case report.
AB  - BACKGROUND: Ceylon krait (Bungarus ceylonicus) is a venomous elapid snake endemic
      to Sri Lanka. It inhabits shaded home gardens and forests in the wet zone of Sri
      Lanka and might creep into houses in the night. Despite frequent encounters with
      humans, reports of envenoming are very rare. CASE PRESENTATION: We report a case
      of a 26-year-old Sri Lankan Sinhalese man with confirmed Ceylon krait envenoming
      presenting with bilateral partial ptosis, ophthalmoplegia, facial muscle
      weakness, and dysphagia. Single fiber electromyography and repetitive nerve
      stimulation confirmed neuromuscular paralysis. He was administered polyvalent
      anti-venom serum immediately following admission without a prompt clinical
      response. Complete recovery was observed 3 days following the bite. CONCLUSIONS:
      Because of the rarity of envenoming, precise and detailed information on the
      clinical manifestations following envenoming is lacking. However, Ceylon krait
      bite can be potentially fatal; so, treating physicians should be aware of species
      identification, habitat, and biting habits and clinical presentation of
      envenoming of Ceylon krait. This case report adds knowledge to the existing
      limited literature available on Ceylon krait envenoming; a rare but potentially
      fatal clinical entity.

PMID- 29169383
TI  - Predictors of a follicular nodule (Thy3) outcome of thyroid fine needle
      aspiration cytology among Saudi patients.
AB  - OBJECTIVE: A retrospective study was performed to evaluate predictors of thyroid
      fine needle aspiration cytology (FNAC) outcomes among Saudis with a thyroid
      nodule. Socio-demographic data, thyroid function status, thyroid parameters,
      ultrasound and cytology results were collected from 269 files of patients with
      thyroid nodules. RESULT: The patients' age was 40 +/- 1.4 years (mean +/- SD),
      and the mean body mass index (BMI) was 30.3 +/- 1.2 kg/m2. The thyroid statuses
      were euthyroid (85.5%), hypothyroidism (7.4%) and hyperthyroidism (7.1%). Young
      age, an absence of irradiation history, and multinodular goitre were protective
      against Thy3 [(OR = 0.05, CI = 003-0.6, P = 0.024), (OR = 0.4, CI = 0.2-0.8, P =
      0.012) and (OR = 2.5, CI = 1.2-5.3, P = 0.016), respectively]; a lower FT3 was
      protective against Thy4 (OR = 0.4, CI = 0.2-0.99, P = 0.046), the absence of
      cervical lymphadenopathy was associated with Thy2 (OR = 2.7, CI = 1.4-5, P =
      0.001), and a solid nodule was associated with Thy2 and Thy3 [(OR = 1.2, CI = 0.3
      0.97, P = 0.040) and (OR = 2.2, CI = 1-4.8, P = 0.039), respectively]. In a
      multivariate analysis, younger age, multinodular goitre, an absence of
      irradiation history and cervical lymphadenopathy were protective against Thy3
      [(OR = 0.04, 95% CI = 0.002-0.96, P = 0.047), (OR = 2.4, 95% CI = 1.0-5.60, P =
      0.039), (OR = 0.4, 95% CI = 0.16-0.94, P = 0.036) and (O R = 0.39, 95% CI = 1
      5.6, P = 0.039), respectively]. In summary, younger age, multinodular goitre, the
      absence of an irradiation history and cervical lymphadenopathy were protective
      against Thy3 in a thyroid nodule.

PMID- 29169384
TI  - Assessing S. mansoni prevalence in Biomphalaria snails in the Gombe ecosystem of
      western Tanzania: the importance of DNA sequence data for clarifying species
      identification.
AB  - BACKGROUND: Snails are essential for the transmission and maintenance of
      schistosomiasis in endemic areas, as they serve as intermediate hosts for
      schistosome parasites. A clear understanding of the snail species present, their
      local distribution and infection status is therefore a prerequisite for effective
      control of schistosomiasis. The purpose of this study was to establish the
      infection status and distribution of Schistosoma mansoni in snails in the Gombe
      area along the shores of Lake Tanganyika in western Tanzania, using both
      detection of cercarial shedding and molecular approaches. METHODS: Snails were
      collected from streams located close to human settlements in Gombe National Park,
      as well as from nearby villages (Kiziba, Mtanga, Mwamgongo and Bugamba) and the
      largest town in the region (Kigoma). Snails were individually exposed to light to
      induce shedding of schistosome larvae, which were examined using a compound light
      microscope. Additionally, the internal transcribed spacer (ITS) region of the
      ribosomal RNA gene cluster was simultaneously amplified in both snails and their
      trematodes using a single polymerase chain reaction (PCR) and sequenced to
      confirm species identification. RESULTS: Snails morphologically identified as
      Biomphalaria pfeifferi were present in all streams except at Mtanga but their
      distribution was patchy in both time and space. Sequencing of PCR products
      indicated that not all snails were B. pfeifferi. None of the snails from Gombe or
      Bugamba shed schistosome larvae, while larvae were shed at all other sites.
      Overall, an infection prevalence of only 12% was observed in snails based on
      cercarial shedding. While 47% of the snails were PCR-positive for the 500 bp ITS
      fragment, which was predicted to indicate infection with S. mansoni, sequence
      data demonstrated that these bands are not species-specific and can be amplified
      from other trematode infections. In addition, a 1000 bp band was amplified in 14%
      of samples, which was identified as a trematode in the family Derogenidae.
      CONCLUSIONS: The results support the previous assumption that B. pfeifferi snails
      may be involved in transmitting schistosomiasis in the area but suggest that the
      community structure of both snails and trematodes may be more complicated than
      previously thought. This emphasises the importance of confirming species
      identifications using sequencing, rather than relying only on PCR-based
      diagnostics or cercarial shedding.

PMID- 29169385
TI  - Standardised Outcomes in Nephrology-Polycystic Kidney Disease (SONG-PKD): study
      protocol for establishing a core outcome set in polycystic kidney disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
      common potentially life threatening inherited kidney disease and is responsible
      for 5-10% of cases of end-stage kidney disease (ESKD). Cystic kidneys may enlarge
      up to 20 times the weight of a normal kidney due to the growth of renal cysts,
      and patients with ADPKD have an increased risk of morbidity, premature mortality,
      and other life-time complications including renal and hepatic cyst and urinary
      tract infection, intracranial aneurysm, diverticulosis, and kidney pain which
      impair quality of life. Despite some therapeutic advances and the growing number
      of clinical trials in ADPKD, the outcomes that are relevant to patients and
      clinicians, such as symptoms and quality of life, are infrequently and
      inconsistently reported. This potentially limits the contribution of trials to
      inform evidence-based decision-making. The Standardised Outcomes in Nephrology
      Polycystic Kidney Disease (SONG-PKD) project aims to establish a consensus-based
      set of core outcomes for trials in PKD (with an initial focus on ADPKD but
      inclusive of all stages) that patients and health professionals identify as
      critically important. METHODS: The five phases of SONG-PKD are: a systematic
      review to identify outcomes that have been reported in existing PKD trials; focus
      groups with nominal group technique with patients and caregivers to identify,
      rank, and describe reasons for their choices; qualitative stakeholder interviews
      with health professionals to elicit individual values and perspectives on
      outcomes for trials involving patients with PKD; an international three-round
      Delphi survey with all stakeholder groups (including patients, caregivers,
      healthcare providers, policy makers, researchers, and industry) to gain consensus
      on critically important core outcome domains; and a consensus workshop to review
      and establish a set of core outcome domains and measures for trials in PKD.
      DISCUSSION: The SONG-PKD core outcome set is aimed at improving the consistency
      and completeness of outcome reporting across ADPKD trials, leading to
      improvements in the reliability and relevance of trial-based evidence to inform
      decisions about treatment and ultimately improve the care and outcomes for people
      with ADPKD.

PMID- 29169386
TI  - Spatiotemporal distribution and population at risk of soil-transmitted helminth
      infections following an eight-year school-based deworming programme in Burundi,
      2007-2014.
AB  - BACKGROUND: Investigating the effect of successive annual deworming rounds on the
      spatiotemporal distribution of infection prevalence and numbers at risk for soil
      transmitted helminths (STHs) can help identify communities nearing elimination
      and those needing further interventions. In this study, we aim to quantify the
      impact of an 8-year mass drug administration (MDA) programme (from 2007 to 2014)
      on the spatiotemporal distribution of prevalence of STH infections and to
      estimate the number of school-aged children infected with STHs in Burundi.
      METHODS: During annual longitudinal school-based surveys in Burundi between 2007
      and 2011, STH infection and anthropometric data for a total of 40,656 children
      were collected; these data were supplemented with data from a national survey
      conducted in 2014. Bayesian model based geostatistics (MBG) were used to generate
      predictive prevalence maps for each STH species and year. The numbers of children
      at-risk of infection per district between 2008 and 2014 were estimated as the
      product of the predictive prevalence maps and population density maps. RESULTS:
      Overall, the degree of spatial clustering of STH infections decreased between
      2008 and 2011; in 2014 the geographical clusters of all STH infections
      reappeared. The reduction in prevalence was small for Ascaris lumbricoides and
      Trichuris trichiura in the centre and central north of the country. Our
      predictive prevalence maps for hookworm indicate a reduction in prevalence along
      the periphery of the country. The predicted number of children infected with any
      STH species decreased substantially between 2007 and 2011, but in 2014 there was
      an increase in the predicted number of children infected with A. lumbricoides and
      T. trichiura. In 2014, the districts with the highest predicted number of
      children infected with A. lumbricoides, T. trichiura and hookworms were Kibuye
      district (n = 128,903), Mabayi district (n = 35,302) and Kiremba (n = 87,511),
      respectively. CONCLUSIONS: While the MDA programme in Burundi resulted in a
      reduction in STH prevalence, this reduction was spatiotemporally heterogeneous,
      with some pockets of high prevalence remaining, suggesting that treatment
      coverage and complementary interventions should be evaluated to improve impact.

PMID- 29169387
TI  - Flotation techniques (FLOTAC and mini-FLOTAC) for detecting gastrointestinal
      parasites in howler monkeys.
AB  - BACKGROUND: Analyses of environmental correlates of the composition of
      gastrointestinal parasite communities in black howler monkeys (Alouatta pigra)
      have been hindered by inadequate calibration techniques of detection and
      quantification methods of the parasites. Here we calibrate samples and compare
      the likelihood of parasite detection using two flotation techniques, FLOTAC and
      Mini-FLOTAC, and compare flotation solution, preservation method and dilution
      ratio for egg detection and counts of the most common parasites (Controrchis spp.
      and Trypanoxyuris spp.) in howler monkeys. RESULTS: For samples preserved in 5%
      formalin, the Mini-FLOTAC technique was the best option for qualitative and
      quantitative copro-microscopic analysis. This technique displays an 83.3% and
      100% detection of Controrchis spp. and Trypanoxyuris spp. infections,
      respectively. For the trematode Controrchis spp., more eggs per gram of feces
      (EPG) were recorded with the flotation solution (FS) #7 (zinc sulfate; specific
      gravity SG = 1.35) at 1:20 and 1:25 dilution than other methods. By contrast, for
      the nematode Trypanoxyuris spp., the best results were recorded with FS1 (sucrose
      and formaldehyde; SG = 1.20) at 1:10 dilution. CONCLUSIONS: We recommend the Mini
      FLOTAC technique for general use with parasite analysis on frugivore/folivores
      like the howler monkey, especially if many samples are analyzed. The technique
      has a high detection rate and the best EPG counts, allowing the qualitative and
      quantitative analysis of parasite load among the species or populations without
      the need for specialized equipment.

PMID- 29169389
TI  - Residential particulate matter and distance to roadways in relation to
      mammographic density: results from the Nurses' Health Studies.
AB  - BACKGROUND: High mammographic density is a strong, well-established breast cancer
      risk factor. Three studies conducted in various smaller geographic settings
      reported inconsistent findings between air pollution and mammographic density. We
      assessed whether particulate matter (PM) exposures (PM2.5, PM2.5-10, and PM10)
      and distance to roadways were associated with mammographic density among women
      residing across the United States. METHODS: The Nurses' Health Studies are
      prospective cohorts for whom a subset has screening mammograms from the 1990s
      (interquartile range 1990-1999). PM was estimated using spatio-temporal models
      linked to residential addresses. Among 3258 women (average age at mammogram 52.7
      years), we performed multivariable linear regression to assess associations
      between square-root-transformed mammographic density and PM within 1 and 3 years
      before the mammogram. For linear regression estimates of PM in relation to
      untransformed mammographic density outcomes, bootstrapped robust standard errors
      are used to calculate 95% confidence intervals (CIs). Analyses were stratified by
      menopausal status and region of residence. RESULTS: Recent PM and distance to
      roadways were not associated with mammographic density in premenopausal women
      (PM2.5 within 3 years before mammogram beta = 0.05, 95% CI -0.16, 0.27; PM2.5-10
      beta = 0, 95%, CI -0.15, 0.16; PM10 beta = 0.02, 95% CI -0.10, 0.13) and
      postmenopausal women (PM2.5 within 3 years before mammogram beta = -0.05, 95% CI 
      0.27, 0.17; PM2.5-10 beta = -0.01, 95% CI -0.16, 0.14; PM10 beta = -0.02, 95% CI 
      0.13, 0.09). Largely null associations were observed within regions. Suggestive
      associations were observed among postmenopausal women in the Northeast (n = 745),
      where a 10-MUg/m3 increase in PM2.5 within 3 years before the mammogram was
      associated with 3.4 percentage points higher percent mammographic density (95% CI
      -0.5, 7.3). CONCLUSIONS: These findings do not support that recent PM or roadway
      exposures influence mammographic density. Although PM was largely not associated
      with mammographic density, we cannot rule out the role of PM during earlier
      exposure time windows and possible associations among northeastern postmenopausal
      women.

PMID- 29169388
TI  - Vitamin D deficiency in critically ill children: a systematic review and meta
      analysis.
AB  - BACKGROUND: Vitamin D deficiency (VDD) has been hypothesized not only to be
      common but also to represent a potentially modifiable risk factor for greater
      illness severity and clinical outcome during critical illness. The objective of
      this systematic review was to determine the frequency of VDD in pediatric
      critical illness and its association with clinical outcomes. METHODS: MEDLINE,
      Embase, and CENTRAL were searched through December 12, 2016, with no date or
      language restrictions. The primary objective was to estimate the prevalence of
      VDD in the pediatric intensive care unit (PICU) and compare vitamin D status with
      healthy control populations. Secondary objectives were to evaluate whether VDD is
      associated with mortality, increased illness severity, PICU interventions, and
      patient clinical course. Random effects meta-analysis was used to calculate
      pooled VDD event rate, compare levels with those of control subjects, and
      evaluate for associations between VDD and clinical outcome. RESULTS: Among 2700
      citations, 17 studies meeting study eligibility were identified. The studies
      reported a total of 2783 critically ill children and had a median sample size of
      120 (range 12-511). The majority of studies used a 25-hydroxyvitamin D [25(OH)D]
      level less than 50 nmol/L to define VDD, and the pooled VDD prevalence was 54.8
      (95% CI 45.4-63.9). Average 25(OH)D levels were significantly lower in PICU
      patients than in healthy control subjects (pooled difference -17.3 nmol/L, 95% CI
      -14.0 to -20.6). In a meta-analysis calculation, we found that VDD was associated
      with increased mortality (OR 1.62, 95% CI 1.11-2.36), illness severity, and need
      for PICU interventions. CONCLUSIONS: Approximately 50% of critically ill children
      have VDD at the time of PICU admission, defined as a blood total 25(OH)D
      concentration under 50 nmol/L. VDD was further determined to be associated with
      greater illness severity, multiple organ dysfunction, and mortality in the PICU
      setting. Clinical trials are required to determine if optimization of vitamin D
      status improves patient outcome. TRIAL REGISTRATION: PROSPERO, CRD42016026617 .
      Registered on 11 January 2016.

PMID- 29169390
TI  - Genomic analysis of bluetongue virus episystems in Australia and Indonesia.
AB  - The distribution of bluetongue viruses (BTV) in Australia is represented by two
      distinct and interconnected epidemiological systems (episystems)-one distributed
      primarily in the north and one in the east. The northern episystem is
      characterised by substantially greater antigenic diversity than the eastern
      episystem; yet the forces that act to limit the diversity present in the east
      remain unclear. Previous work has indicated that the northern episystem is linked
      to that of island South East Asia and Melanesia, and that BTV present in
      Indonesia, Papua New Guinea and East Timor, may act as source populations for new
      serotypes and genotypes of BTV to enter Australia's north. In this study, the
      genomes of 49 bluetongue viruses from the eastern episystem and 13 from Indonesia
      were sequenced and analysed along with 27 previously published genome sequences
      from the northern Australian episystem. The results of this analysis confirm that
      the Australian BTV population has its origins in the South East Asian/Melanesian
      episystem, and that incursions into northern Australia occur with some
      regularity. In addition, the presence of limited genetic diversity in the eastern
      episystem relative to that found in the north supports the presence of
      substantial, but not complete, barriers to gene flow between the northern and
      eastern Australian episystems. Genetic bottlenecks between each successive
      episystem are evident, and appear to be responsible for the reduction in BTV
      genetic diversity observed in the north to south-east direction.

PMID- 29169391
TI  - Factors associated with deaths in 'Elderly Housing with Care Services' in Japan:
      a cross-sectional study.
AB  - BACKGROUND: Although the Japanese government has expanded its 'Elderly Housing
      with Care Services' (EHCS) to ensure sufficient places of death for the elderly,
      resident deaths have occurred in less than 30% of the facilities. Our purpose was
      to identify the factors associated with residents' deaths in the EHCS, especially
      within the areas that are expected to have a large increase in the number of
      deaths. METHODS: Our cross-sectional study involved all EHCS (N = 412) in Japan's
      Tokyo, Kanagawa prefecture and used self-administered questionnaire data that the
      EHCS directors completed. In addition, we accessed the national statistics
      related to the municipal characteristics of the cities where the EHCS were
      located. These sources provided information about health care provision for the
      residents as well as facility/resident/regional characteristics that could
      potentially be associated with residents' deaths in the EHCS. Based on this
      information, a sequential multiple logistic regression analysis was performed.
      First, we included in-facility health care provision (presence of nursing staff)
      and facility/residents/regional characteristics in Model 1. Next, visiting nurse
      agency's care provision was included in Model 2. Finally, we included community
      hospitals or clinical care provision in Model 3. RESULTS: One hundred and fifty
      four facilities answered the questionnaire (response rate: 37.4%). A total of 114
      facilities were analysed. In-facility residents' deaths occurred in more than
      half (54.4%) of the facilities. After adjusting for all variables (Model 3), end
      of-life (EOL) care provision from community hospitals or clinics, the number of
      years since establishment and the number of residents were significantly
      associated with residents' deaths. In Model 2, visiting nurse's EOL care
      provision was significantly associated with residents' death. CONCLUSION: Our
      results suggest that in order to accommodate residents' deaths, the government or
      the facility's directors should promote the cooperation between EHCS facilities
      and community hospitals or clinics for in-residents' EOL care. Furthermore, as
      the results suggest that community nurses contribute to the occurrences of death
      by collaborating with the physician, promoting cooperation with visiting nurse
      agencies may be also needed.

PMID- 29169392
TI  - Prognostic role of nodal ratio, LODDS, pN in patients with pancreatic cancer with
      venous involvement.
AB  - BACKGROUND: The UICC/AJCC TNM staging system classifies lymph nodes as N0 and N1
      in pancreatic cancer. Aim of the study is to determine whether the number of
      examine nodes, the nodal ratio (NR) and the logarithm odds of positive lymph
      nodes (LODDS) may better stratify the prognosis of patients undergoing
      pancreatectomy combined with venous resection for pancreatic cancer with venous
      involvement. METHODS: A multicenter database of 303 patients undergoing
      pancreatectomy in 9 Italian referral centers was analyzed. The prognostic impact
      of number of retrieved and examined nodes, NR, LODDS was analyzed and compared
      with ROC curves analysis, Pearson test, univariate and multivariate analysis.
      RESULTS: The number of metastatic nodes, pN, the NR and LODDS was significantly
      correlated with survival at multivariate analyses. The corresponding AUC for the
      number of metastatic nodes, pN, the NR and LODDS were 0.66, 0.69, 0.63 and 0.65,
      respectively. The Pearson test showed a significant correlation between the
      number of retrieved lymph nodes and number of metastatic nodes, pN and the NR.
      LODDS had the lower coefficient correlation. Concerning N1 patients, the NR, the
      LODDS and the number of metastatic nodes were able to significantly further
      stratify survival (p = 0.040; p = 0.046; p = 0.038, respectively). CONCLUSIONS:
      The number of examined lymph nodes, the NR and LODDS are useful for further
      prognostic stratification of N1 patients in the setting of pancreatectomy
      combined with PV/SMV resection. No superiority of one over the others methods was
      detected.

PMID- 29169393
TI  - A systematic review and meta-analysis of online versus alternative methods for
      training licensed health care professionals to deliver clinical interventions.
AB  - BACKGROUND: Online training is growing in popularity and yet its effectiveness
      for training licensed health professionals (HCPs) in clinical interventions is
      not clear. We aimed to systematically review the literature on the effectiveness
      of online versus alternative training methods in clinical interventions for
      licensed Health Care Professionals (HCPs) on outcomes of knowledge acquisition,
      practical skills, clinical behaviour, self-efficacy and satisfaction. METHODS:
      Seven databases were searched for randomised controlled trials (RCTs) from
      January 2000 to June 2015. Two independent reviewers rated trial quality and
      extracted trial data. Comparative effects were summarised as standardised mean
      differences (SMD) and 95% confidence intervals. Pooled effect sizes were
      calculated using a random-effects model for three contrasts of online versus (i)
      interactive workshops (ii) taught lectures and (iii) written/electronic manuals.
      RESULTS: We included 14 studies with a total of 1089 participants. Most trials
      studied medical professionals, used a workshop or lecture comparison, were of
      high risk of bias and had small sample sizes (range 21-183). Using the GRADE
      approach, we found low quality evidence that there was no difference between
      online training and an interactive workshop for clinical behaviour SMD 0.12 (95%
      CI -0.13 to 0.37). We found very low quality evidence of no difference between
      online methods and both a workshop and lecture for knowledge (workshop: SMD 0.04
      (95% CI -0.28 to 0.36); lecture: SMD 0.22 (95% CI: -0.08, 0.51)). Lastly,
      compared to a manual (n = 3/14), we found very low quality evidence that online
      methods were superior for knowledge SMD 0.99 (95% CI 0.02 to 1.96). There were
      too few studies to draw any conclusions on the effects of online training for
      practical skills, self-efficacy, and satisfaction across all contrasts.
      CONCLUSIONS: It is likely that online methods may be as effective as alternative
      methods for training HCPs in clinical interventions for the outcomes of knowledge
      and clinical behaviour. However, the low quality of the evidence precludes
      drawing firm conclusions on the relative effectiveness of these training methods.
      Moreover, the confidence intervals around our effect sizes were large and could
      encompass important differences in effectiveness. More robust, adequately powered
      RCTs are needed.

PMID- 29169394
TI  - Physical activity and activity space in patients with pulmonary fibrosis not
      prescribed supplemental oxygen.
AB  - BACKGROUND: Patients with pulmonary fibrosis (PF) have impaired quality of life,
      and research suggests that dyspnea and physical activity are primary drivers. As
      PF progresses, some patients notice the disease "shrinks their worlds". The
      objective of this study is to describe movement (both physical activity and
      activity space) in a cohort of patients with PF of various etiologies who have
      not been prescribed supplemental oxygen (O2). METHODS: Subjects with PF not on
      supplemental O2 during the day were enrolled from across the U.S. from August
      2013 to October 2015. At enrollment, each subject completed questionnaires and,
      for seven consecutive days, wore an accelerometer and GPS tracker. RESULTS: One
      hundred ninety-four subjects had a confirmed diagnosis of PF and complete,
      analyzable GPS data. The cohort was predominantly male (56%), Caucasian (95%) and
      had idiopathic pulmonary fibrosis (30%) or connective tissue disease related-PF
      (31%). Subjects walked a median 7497 (interquartile range [IQR] 5766-9261) steps
      per day. Steps per day were correlated with symptoms and several quality of life
      domains. In a model controlling for age, body mass index, wrist- (vs. waist) worn
      accelerometer and percent predicted diffusing capacity (DLCO%), fatigue (beta
      coefficient = -51.5 +/- 11.7, p < 0.0001) was an independent predictor of steps
      per day (model R2=0.34). CONCLUSIONS: Patients with PF, who have not been
      prescribed O2 for use during the day, have wide variability in their mobility.
      Day-to-day physical activity is related to several domains that impact quality of
      life, but GPS-derived activity space is not. Wearable data collection devices may
      be used to determine whether and how therapeutic interventions impact movement in
      PF patients. TRIAL REGISTRATION: NCT01961362 . Registered 9 October, 2013.

PMID- 29169395
TI  - Genome-wide analysis of E. coli cell-gene interactions.
AB  - BACKGROUND: The pursuit of standardization and reliability in synthetic biology
      has achieved, in recent years, a number of advances in the design of more
      predictable genetic parts for biological circuits. However, even with the
      development of high-throughput screening methods and whole-cell models, it is
      still not possible to predict reliably how a synthetic genetic construct
      interacts with all cellular endogenous systems. This study presents a genome-wide
      analysis of how the expression of synthetic genes is affected by systematic
      perturbations of cellular functions. We found that most perturbations modulate
      expression indirectly through an effect on cell size, putting forward the
      existence of a generic Size-Expression interaction in the model prokaryote
      Escherichia coli. RESULTS: The Size-Expression interaction was quantified by
      inserting a dual fluorescent reporter gene construct into each of the 3822 single
      gene deletion strains comprised in the KEIO collection. Cellular size was
      measured for single cells via flow cytometry. Regression analyses were used to
      discriminate between expression-specific and gene-specific effects. Functions of
      the deleted genes broadly mapped onto three systems with distinct primary
      influence on the Size-Expression map. Perturbations in the Division and
      Biosynthesis (DB) system led to a large-cell and high-expression phenotype. In
      contrast, disruptions of the Membrane and Motility (MM) system caused small-cell
      and low-expression phenotypes. The Energy, Protein synthesis and Ribosome (EPR)
      system was predominantly associated with smaller cells and positive feedback on
      ribosome function. CONCLUSIONS: Feedback between cell growth and gene expression
      is widespread across cell systems. Even though most gene disruptions proximally
      affect one component of the Size-Expression interaction, the effect therefore
      ultimately propagates to both. More specifically, we describe the dual impact of
      growth on cell size and gene expression through cell division and ribosomal
      content. Finally, we elucidate aspects of the tight control between swarming,
      gene expression and cell growth. This work provides foundations for a systematic
      understanding of feedbacks between genetic and physiological systems.

PMID- 29169396
TI  - Apolipoprotein E gene polymorphism modifies fasting total cholesterol
      concentrations in response to replacement of dietary saturated with
      monounsaturated fatty acids in adults at moderate cardiovascular disease risk.
AB  - BACKGROUND: Consumption of <=10% total energy from fat as saturated fatty acids
      (SFA) is recommended for cardiovascular disease risk reduction in the UK; however
      there is no clear guidance on the optimum replacement nutrient. Lipid-associated
      single-nucleotide polymorphisms (SNPs) have been shown to modify the lipid
      responses to dietary fat interventions. Hence, we performed a retrospective
      analysis in 120 participants from the Dietary Intervention and VAScular function
      (DIVAS) study to investigate whether lipoprotein lipase (LPL) and apolipoprotein
      E (APOE) SNPs modify the fasting lipid response to replacement of SFA with
      monounsaturated (MUFA) or n-6 polyunsaturated (PUFA) fatty acids. METHODS: The
      DIVAS study was a randomized, single-blinded, parallel dietary intervention study
      performed in adults with a moderate cardiovascular risk who received one of three
      isoenergetic diets rich in SFA, MUFA or n-6 PUFA for 16 weeks. RESULTS: After the
      16-week intervention, a significant diet-gene interaction was observed for
      changes in fasting total cholesterol (P = 0.001). For the APOE SNP rs1064725,
      only TT homozygotes showed a significant reduction in total cholesterol after the
      MUFA diet (n = 33; -0.71 +/- 1.88 mmol/l) compared to the SFA (n = 38; 0.34 +/-
      0.55 mmol/l) or n-6 PUFA diets (n = 37; -0.08 +/- 0.73 mmol/l) (P = 0.004). None
      of the interactions were statistically significant for the other SNPs.
      CONCLUSIONS: In summary, our findings have demonstrated a greater sensitivity of
      the APOE SNP rs1064725 to dietary fat composition, with a total cholesterol
      lowering effect observed following substitution of SFA with MUFA but not n-6
      PUFA. Further large intervention studies incorporating prospective genotyping are
      required to confirm or refute our findings. TRIAL REGISTRATION: The trial was
      registered at www.clinicaltrials.gov as NCT01478958.

PMID- 29169397
TI  - Application of discrete choice experiments to enhance stakeholder engagement as a
      strategy for advancing implementation: a systematic review.
AB  - BACKGROUND: One of the key strategies to successful implementation of effective
      health-related interventions is targeting improvements in stakeholder engagement.
      The discrete choice experiment (DCE) is a stated preference technique for
      eliciting individual preferences over hypothetical alternative scenarios that is
      increasingly being used in health-related applications. DCEs are a dynamic
      approach to systematically measure health preferences which can be applied in
      enhancing stakeholder engagement. However, a knowledge gap exists in
      characterizing the extent to which DCEs are used in implementation science.
      METHODS: We conducted a systematic literature search (up to December 2016) of the
      English literature to identify and describe the use of DCEs in engaging
      stakeholders as an implementation strategy. We searched the following electronic
      databases: MEDLINE, Econlit, PsychINFO, and the CINAHL using mesh terms. Studies
      were categorized according to application type, stakeholder(s), healthcare
      setting, and implementation outcome. RESULTS: Seventy-five publications were
      selected for analysis in this systematic review. Studies were categorized by
      application type: (1) characterizing demand for therapies and treatment
      technologies (n = 32), (2) comparing implementation strategies (n = 22), (3)
      incentivizing workforce participation (n = 11), and (4) prioritizing
      interventions (n = 10). Stakeholders included providers (n = 27), patients (n =
      25), caregivers (n = 5), and administrators (n = 2). The remaining studies (n =
      16) engaged multiple stakeholders (i.e., combination of patients, caregivers,
      providers, and/or administrators). The following implementation outcomes were
      discussed: acceptability (n = 75), appropriateness (n = 34), adoption (n = 19),
      feasibility (n = 16), and fidelity (n = 3). CONCLUSIONS: The number of DCE
      studies engaging stakeholders as an implementation strategy has been increasing
      over the past decade. As DCEs are more widely used as a healthcare assessment
      tool, there is a wide range of applications for them in stakeholder engagement.
      The DCE approach could serve as a tool for engaging stakeholders in
      implementation science.

PMID- 29169398
TI  - Identifying accessible prognostic factors for breast cancer relapse: a case-study
      on 405 histologically confirmed node-negative patients.
AB  - BACKGROUND: Histologically, node-negative breast cancer generally have a good
      prognosis. However, 10 to 30% of the cases present local relapses or metastasis.
      This group of people has high chances of remission if detected early. The aim of
      this study is to identify financial affordability for developing countries to
      adjust treatment. METHODS: We selected 405 patients with histologically confirmed
      node-negative breast cancer in our institution between January 2001 and December
      2003. Patients with metastasis were excluded. The statistical analysis was
      conducted using SPSS ver. 18 (SPSS, Inc., Chicago, Illinois). RESULTS: The medial
      age was 51 years old. The medial tumor size was 35.4 mm. Clinically, 67.2% of the
      patients were staged cT2 and 63.2%, cN1i. Breast conservation was achieved in 41%
      of cases. In the histologic examination, the medial size was 30 mm. Grade III
      tumors were found in 50.1% of patients and positive hormonal receptors in 53.4%.
      The mean number of lymph nodes was 14. Eight patients had neoadjuvant
      chemotherapy. Adjuvant locoregional radiation and adjuvant chemotherapy were
      prescribed respectively in 70.6 and 64.4% of cases. 59.7% had adjuvant hormonal
      therapy. The follow-up showed 17.7% cases of relapse either locally or in a
      metastatic way in a mean time of 57.4 months. The disease-free survival at 5
      years was 82.1%, and the overall survival for the same period was 91.5%. The
      histologic tumor size and the grade and number of lymph node dissected were shown
      to be influencing the disease-free survival. Radiation therapy and hormone
      therapy showed improved disease-free survival and overall survival. CONCLUSION:
      Our study found interesting results that may help personalize the treatment
      especially for patient living in underdeveloped countries, but further studies
      are needed to evaluate those and more accessible prognostic factors for a more
      accessible healthcare.

PMID- 29169399
TI  - The effects of using the PReDicT Test to guide the antidepressant treatment of
      depressed patients: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Antidepressant medication is commonly used to treat depression.
      However, many patients do not respond to the first medication prescribed and
      improvements in symptoms are generally only detectable by clinicians 4-6 weeks
      after the medication has been initiated. As a result, there is often a long delay
      between the decision to initiate an antidepressant medication and the
      identification of an effective treatment regimen. Previous work has demonstrated
      that antidepressant medications alter subtle measures of affective cognition in
      depressed patients, such as the appraisal of facial expression. Furthermore,
      these cognitive effects of antidepressants are apparent early in the course of
      treatment and can also predict later clinical response. This trial will assess
      whether an electronic test of affective cognition and symptoms (the Predicting
      Response to Depression Treatment Test; PReDicT Test) can be used to guide
      antidepressant treatment in depressed patients and, therefore, hasten treatment
      response compared to a control group of patients treated as usual.
      METHODS/DESIGN: The study is a randomised, two-arm, multi-centre, open-label,
      clinical investigation of a medical device, the PReDicT Test. It will be
      conducted in five European countries (UK, France, Spain, Germany and the
      Netherlands) in depressed patients who are commencing antidepressant medication.
      Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm)
      or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as
      per current standard guidelines in their particular country. Patients in the
      PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of
      treatment. If the test indicates non-response to the treatment, physicians will
      be advised to immediately alter the patient's antidepressant therapy by dose
      escalation or switching to another compound. The primary outcome of the study is
      the proportion of patients showing a clinical response (defined as 50% or greater
      decrease in baseline scores of depression measured using the Quick Inventory of
      Depressive Symptoms - Self-Rated questionnaire) at week 8. Health economic and
      acceptability data will also be collected and analysed. DISCUSSION: This trial
      will test the clinical efficacy, cost-effectiveness and acceptability of using
      the novel PReDicT Test to guide antidepressant treatment selection in depressed
      patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02790970 . Registered on
      30 March 2016.

PMID- 29169400
TI  - Hypermethylation and loss of retinoic acid receptor responder 1 expression in
      human choriocarcinoma.
AB  - BACKGROUND: Human placental development resembles tumorigenesis, due to the
      invasive and fusogenic potential of trophoblasts. However, these features are
      tightly controlled in trophoblasts. Disturbance of this spatial and temporal
      regulation is thought to contribute to the rare formation of choriocarcinomas.
      Promoter hypermethylation and loss of the tumor suppressor Retinoic acid receptor
      responder 1 (RARRES1) were shown to contribute to cancer progression. Our study
      investigated the epigenetic and transcriptional regulation of RARRES1 in healthy
      human placenta in comparison to choriocarcinoma cell lines and cases. METHODS:
      Three choriocarcinoma cell lines (Jeg-3, JAR and BeWo) were treated with three
      different retinoic acid derivates (Am580, Tazarotene and all-trans retinoic acid)
      and 5-aza-2'-deoxycytidine. We analyzed RARRES1 promoter methylation by
      pyrosequencing and performed realtime-PCR quantification to determine RARRES1
      expression in placental tissue and trophoblastic cell lines. Additionally,
      RARRES1 was stained in healthy placentas and in biopsies of choriocarcinoma cases
      (n = 10) as well as the first trimester trophoblast cell line Swan71 by
      immunofluorescence and immunohistochemistry. RESULTS: In the choriocarcinoma cell
      lines, RARRES1 expression could not be induced by sole retinoic acid treatment.
      Stimulation with 5-aza-2'-deoxycytidine significantly induced RARRES1 expression,
      which then could be further increased with Am580, Tazarotene and all-trans
      retinoic acid. In comparison to healthy placenta, choriocarcinoma cell lines
      showed a hypermethylation of the RARRES1 promoter, which correlated with a
      reduced RARRES1 expression. In concordance, RARRES1 protein expression was lost
      in choriocarcinoma tissue. Additionally, in the trophoblastic cell line Swan71,
      we found a significant induction of RARRES1 expression with increased cell
      density, during mitosis and in syncytial knots. CONCLUSIONS: Our findings showed
      that RARRES1 expression is absent in choriocarcinoma due to promoter methylation.
      Based on our analysis, we hypothesize that RARRES1 might exert tumor suppressive
      functions in multiple cellular processes (e.g. cell cycle regulation, adhesion,
      invasion and apoptosis).

PMID- 29169401
TI  - Treatment of splenic trauma in Norway: a retrospective cohort study.
AB  - BACKGROUND: Non-operative management of splenic injuries has become the treatment
      of choice in hemodynamically stable patients over the last decades. The aim of
      the study is to describe the incidence, initial treatment and early outcome of
      patients with splenic injuries on a national level. METHODS: All hospitals in
      Norway admitting trauma patients were invited to participate in the study. The
      study period was January through December 2013. The hospitals delivered anonymous
      data on primarily admitted patients with splenic injury. RESULTS: Three of the
      four regional trauma centers and 26 of the remaining 33 acute care hospitals
      delivered data on a total of 151 patients with splenic injury indicating an
      incidence of 4 splenic injuries per 100,000 inhabitants/year, and a median of 4
      splenic injuries per hospital per year. A total of 128 (85%) patients were
      successfully treated non-operatively including 20 patients who underwent an
      angiographic procedure. The remaining 23 (15%) patients underwent open
      splenectomy or spleen-preserving surgery. CONCLUSION: Most patients with splenic
      injuries are managed non-operatively. Despite the low number of splenic injuries
      per hospital, the results indicate satisfactory outcome on a national level.

PMID- 29169402
TI  - Age, exercise, and the outcome of sepsis.
AB  - We report on the increasingly important need to diagnose and care for the elderly
      with sepsis as a distinct patient population. We share an overview of age-related
      changes in sepsis physiology and the potential role of exercise.See related
      research by Tyml et al.,
      https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1783-1.

PMID- 29169403
TI  - Improving health promotion through central rating of interventions: the need for
      Responsive Guidance.
AB  - BACKGROUND: In several countries, attempts are made to improve health promotion
      by centrally rating the effectiveness of health promotion interventions. The
      Dutch Effectiveness Rating System (ERS) for health promotion interventions is an
      improvement-oriented approach in which multi-disciplinary expert committees rate
      available health promotion interventions as 'theoretically sound', 'probably
      effective' or 'proven effective'. The aim of this study is to explore the
      functioning of the ERS and the perspective of researchers, policy-makers and
      practitioners regarding its contribution to improvement. METHODS: We interviewed
      53 selected key informants from research, policy and practice in the Netherlands
      and observed the assessment of 12 interventions. RESULTS: Between 2008 and 2012,
      a total of 94 interventions were submitted to the ERS, of which 23 were rejected,
      58 were rated as 'theoretically sound', 10 were rated as 'probably effective' and
      3 were rated as 'proven effective'. According to participants, the ERS was
      intended to facilitate both the improvement of available interventions and the
      improvement of health promotion in practice. While participants expected that
      describing and rating interventions promoted learning and enhanced the
      transferability of interventions, they were concerned that the ERS approach was
      not suitable for guiding intervention development and improving health promotion
      in practice. The expert committees that assessed the interventions struggled with
      a lack of norms for the relevance of effects and questions about how effects
      should be studied and rated. Health promotion practitioners were concerned that
      the ERS neglected the local adaptation of interventions and did not encourage the
      improvement of aspects like applicability and costs. Policy-makers and
      practitioners were worried that the lack of proven effectiveness legitimised
      cutbacks rather than learning and advancing health promotion. CONCLUSION: While
      measuring and centrally rating the effectiveness of interventions can be
      beneficial, the evidence based-inspired ERS approach is too limited to guide both
      intervention development and the improvement of health promotion in practice. To
      better contribute to improving health promotion, a more reflexive and responsive
      guidance approach is required, namely one which stimulates the improvement of
      different intervention aspects, provides targeted recommendations to
      practitioners and provides feedback to those who develop and rate interventions.

PMID- 29169404
TI  - A mechanistic study of Toxoplasma gondii ROP18 inhibiting differentiation of
      C17.2 neural stem cells.
AB  - BACKGROUND: Congenital infection of Toxoplasma gondii is an important factor
      causing birth defects. The neural stem cells (NSCs) are found to be one of the
      target cells for the parasite during development of the brain. As a key virulence
      factor of the parasite that hijacks host cellular functions, ROP18 has been
      demonstrated to mediate the inhibition of host innate and adaptive immune
      responses through specific binding different host immunity related molecules.
      However, its pathogenic actions in NSCs remain elusive. RESULTS: In the present
      study, ROP18 recombinant adenovirus (Ad-ROP18) was constructed and used to infect
      C17.2 NSCs. After 3d- or 5d-culture in differentiation medium, the
      differentiation of C17.2 NSCs and the activity of the Wnt/beta-catenin signaling
      pathway were detected. The results showed that the protein level of betaIII
      tubulin, a marker of neurons, in the Ad-ROP18-transfected C17.2 NSCs was
      significantly decreased, indicating that the differentiation of C17.2 NSCs was
      inhibited by the ROP18. The beta-catenin level in the Ad-ROP18-transfected C17.2
      NSCs was found to be lower than that in the Ad group. Also, neurogenin1 (Ngn1)
      and neurogenin2 (Ngn2) were downregulated significantly (P < 0.05) in the Ad
      ROP18-transfected C17.2 NSCs compared to the Ad group. Accordingly, the TOP
      flash/FOP flash dual-luciferase report system showed that the transfection of Ad
      ROP18 decreased the Wnt/beta-catenin pathway activity in the C17.2 NSCs.
      CONCLUSIONS: The inhibition effect of the ROP18 from T. gondii (TgROP18) on the
      neuronal differentiation of C17.2 NSCs was at least partly mediated through
      inhibiting the activity of the Wnt/beta-catenin signaling pathway, eventually
      resulting in the downregulation of Ngn1 and Ngn2. The findings help to better
      understand potential mechanisms of brain pathology induced by TgROP18.

PMID- 29169405
TI  - Atypical Creutzfeldt-Jakob disease with PrP-amyloid plaques in white matter:
      molecular characterization and transmission to bank voles show the M1 strain
      signature.
AB  - Amyloid plaques formed by abnormal prion protein (PrPSc) aggregates occur with
      low frequency in Creutzfeldt-Jakob disease, but represent a pathological hallmark
      of three relatively rare disease histotypes, namely variant CJD, sporadic CJDMV2K
      (methionine/valine at PRNP codon 129, PrPSc type 2 and kuru-type amyloid plaques)
      and iatrogenic CJDMMiK (MM at codon 129, PrPSc of intermediate type and kuru
      plaques). According to recent studies, however, PrP-amyloid plaques involving the
      subcortical and deep nuclei white matter may also rarely occur in CJDMM1 (MM at
      codon 129 and PrPSc type 1), the most common CJD histotype.To further
      characterize the phenotype of atypical CJDMM1 with white matter plaques (p
      CJDMM1) and unravel the basis of amyloid plaque formation in such cases, we
      compared clinical and histopathological features and PrPSc physico-chemical
      properties between 5 p-CJDMM1 and 8 typical CJDMM1 brains lacking plaques.
      Furthermore, transmission properties after bioassay in two genetic lines of bank
      voles were also explored in the two groups.All 5 p-CJDMM1 cases had a disease
      duration longer than one year. Three cases were classified as sporadic CJDMM1,
      one as sporadic CJDMM1 + 2C and one as genetic CJDE200K-MM1. Molecular mass,
      protease sensitivity and thermo-solubilization of PrPSc aggregates did not differ
      between p-CJDMM1 and classical CJDMM1 cases. Likewise, transmission properties
      such as incubation time, lesion profile and PrPSc properties in bank voles also
      matched in the two groups.The present data further define the clinical-pathologic
      phenotype of p-CJDMM1, definitely establish it as a distinctive CJD histotype and
      demonstrate that PrP-plaque formation in this histotype is not a strain-specific
      feature. Since cases lacking amyloid plaques may also manifest a prolonged (i.e.
      > than one year) disease course, unidentified, host-specific factors likely play
      a significant role, in addition to disease duration, in generating white matter
      PrP-amyloid plaques in p-CJDMM1.

PMID- 29169406
TI  - Extracellular cathepsin L stimulates axonal growth in neurons.
AB  - OBJECTIVE: Cathepsin L, a lysosomal endopeptidase expressed in most eukaryotic
      cells, is a member of the papain-like family of cysteine proteases. Although
      commonly recognized as a lysosomal protease, cathepsin L is also secreted and
      involved in the degradation of extracellular matrix proteins. Previous studies
      demonstrated that the secretion of cathepsin L was stimulated by basic fibroblast
      growth factor (bFGF) and bFGF-enhanced axonal terminal sprouting of motor
      neurons. Based on these results, although it has never been directly
      investigated, we hypothesized that extracellular cathepsin L may induce axonal
      growth. RESULTS: To confirm the hypothesis, the axonal growth activity of
      recombinant cathepsin L was evaluated in cultured cortical and spinal cord
      neurons. Treatment with recombinant cathepsin L significantly enhanced axonal
      growth, but not dendritic growth. This result indicated that extracellular
      cathepsin L may act as a new neuronal network modulator.

PMID- 29169409
TI  - Characteristic pro-inflammatory cytokines and host defence cathelicidin peptide
      produced by human monocyte-derived macrophages infected with Neospora caninum.
AB  - Neospora caninum is a coccidian intracellular protozoan capable of infecting a
      wide range of mammals, although severe disease is mostly reported in dogs and
      cattle. Innate defences triggered by monocytes/macrophages are key in the
      pathogenesis of neosporosis, as these cells are first-line defenders against
      intracellular infections. The aim of this study was to characterize infection and
      innate responses in macrophages infected with N. caninum using a well-known cell
      model to study macrophage functions (human monocyte THP-1 cells). Intracellular
      invasion of live tachyzoites occurred as fast as 4 h (confirmed with
      immunofluorescence microscopy using N. caninum-specific antibodies). Macrophages
      infected by N. caninum had increased expression of pro-inflammatory cytokines
      (TNFalpha, IL-1beta, IL-8, IFNgamma). Interestingly, N. caninum induced
      expression of host-defence peptides (cathelicidins), a mechanism of defence never
      reported for N. caninum infection in macrophages. The expression of cytokines and
      cathelicidins in macrophages invaded by N. caninum was mediated by mitogen
      activated protein kinase (MEK 1/2). Secretion of such innate factors from N.
      caninum-infected macrophages reduced parasite internalization and promoted the
      secretion of pro-inflammatory cytokines in naive macrophages. We concluded that
      rapid invasion of macrophages by N. caninum triggered protective innate defence
      mechanisms against intracellular pathogens.

PMID- 29169407
TI  - The clinical significance of plasma clusterin and Abeta in the longitudinal
      follow-up of patients with Alzheimer's disease.
AB  - BACKGROUND: Clusterin and beta-amyloid (Abeta) are involved in the pathogenesis
      of Alzheimer's disease (AD). The clinical significance of plasma clusterin and
      Abeta in AD progression remains controversial. METHODS: We recruited 322 patients
      with AD and 88 controls between August 2012 and June 2013. All participants were
      evaluated at baseline with a clinical assessment, Mini-Mental State Examination
      (MMSE), and Clinical Dementia Rating (CDR) scales. Patients with AD were
      evaluated annually with the MMSE and Neuropsychiatric Inventory (NPI) scale
      during the 2-year follow-up period. The levels of plasma clusterin, Abeta1-40,
      and Abeta1-42 at baseline were analyzed to study the longitudinal changes in the
      patient scores on the MMSE and NPI during the follow-up period. RESULTS: Patients
      in the highest tertile of plasma clusterin levels showed significantly lower MMSE
      scores than those in the lowest tertile (p = 0.04). After adjustment for multiple
      covariates using the generalized estimating equation analysis, there was a
      significant decrease in the MMSE scores over the 2-year follow-up period among AD
      patients in the highest tertile of plasma clusterin levels compared with those in
      the lowest tertile (-2.09, 95% confidence interval (CI) = -3.67 to -0.51, p =
      0.01). In apolipoprotein E (ApoE)4-positive AD patients, baseline measurements of
      the ratio of plasma Abeta1-42/Abeta1-40 in the highest tertile predicted an
      increase in NPI agitation/aggression scores over the 2-year follow-up period
      (6.06, 95% CI = 1.20-10.62, p = 0.02). CONCLUSIONS: Plasma clusterin could serve
      as a biomarker for the severity of cognitive decline. Plasma Abeta in ApoE4
      positive AD could predict long-term agitation/aggression symptoms.

PMID- 29169408
TI  - The bacterial interlocked process ONtology (BiPON): a systemic multi-scale
      unified representation of biological processes in prokaryotes.
AB  - BACKGROUND: High-throughput technologies produce huge amounts of heterogeneous
      biological data at all cellular levels. Structuring these data together with
      biological knowledge is a critical issue in biology and requires integrative
      tools and methods such as bio-ontologies to extract and share valuable
      information. In parallel, the development of recent whole-cell models using a
      systemic cell description opened alternatives for data integration. Integrating a
      systemic cell description within a bio-ontology would help to progress in whole
      cell data integration and modeling synergistically. RESULTS: We present BiPON, an
      ontology integrating a multi-scale systemic representation of bacterial cellular
      processes. BiPON consists in of two sub-ontologies, bioBiPON and modelBiPON.
      bioBiPON organizes the systemic description of biological information while
      modelBiPON describes the mathematical models (including parameters) associated
      with biological processes. bioBiPON and modelBiPON are related using bridge rules
      on classes during automatic reasoning. Biological processes are thus
      automatically related to mathematical models. 37% of BiPON classes stem from
      different well-established bio-ontologies, while the others have been manually
      defined and curated. Currently, BiPON integrates the main processes involved in
      bacterial gene expression processes. CONCLUSIONS: BiPON is a proof of concept of
      the way to combine formally systems biology and bio-ontology. The knowledge
      formalization is highly flexible and generic. Most of the known cellular
      processes, new participants or new mathematical models could be inserted in
      BiPON. Altogether, BiPON opens up promising perspectives for knowledge
      integration and sharing and can be used by biologists, systems and computational
      biologists, and the emerging community of whole-cell modeling.

PMID- 29169410
TI  - miR-767-3p Inhibits Growth and Migration of Lung Adenocarcinoma Cells by
      Regulating CLDN18.
AB  - Claudin18 (CLDN18) is necessary for intercellular junctions and is reported to be
      involved in cell migration and metastasis, making it like an oncogene in various
      cancer types. However, the biological function and regulatory mechanisms of
      CLDN18 in lung adenocarcinoma are not yet clear. In this study, we found
      downregulation of miR-767-3p and upregulation of CLDN18 in lung adenocarcinoma
      tissue and cell lines. In addition, there was a negative correlation between the
      expression of miR-767-3p and CLDN18 in lung adenocarcinoma. Double luciferase
      reporter gene analysis showed that miR-767-3p modulates the expression of CLDN18
      by binding its 3'-untranslated regions (3'-UTR). Knockdown of CLDN18 results in a
      decrease in the growth, migration, and invasion of lung adenocarcinoma cells.
      Although overexpression of miR-767-3p inhibits lung adenocarcinoma cell growth
      and migration, these effects can be rescued by reexpressing CLDN18. In summary,
      the data suggest that miR-767-3p inhibits tumor cell proliferation, migration,
      and invasion by targeting CLDN18, providing a promising therapeutic target for
      lung adenocarcinoma.

PMID- 29169411
TI  - [Lung injury in ovalbumin-challenged asthma mice induced by high-dose PM2.5 and
      its mechanism].
AB  - Objective To investigate the degree of lung injury induced by different doses of
      particulate matter with diameters <=2.5 microm (PM2.5) in asthmatic mice. Methods
      Male BALB/c mice were randomly divided into normal control group, ovalbumin (OVA)
      asthma group, 1, 5, 15 mg/mL PM2.5 treated OVA asthma group. The bronchoalveolar
      lavage fluid (BALF) was collected and the number of white blood cells was
      observed by Gimsa staining. ELISA was used to determine the concentrations of
      serum cytokines interferon gamma (IFN-gamma), interleukin 17 (IL-17) and IL-10 in
      the peripheral blood of mice. Real-time quantitative PCR was performed to detect
      the mRNA expression levels of Toll-like receptor 4 (TLR4), nuclear factor-kappaB
      (NF-kappaB) in peripheral blood mononuclear cells (PBMCs). The levels of T-bet,
      RORgammat and FOXP3 were tested by Western blotting. The lung tissues were
      collected and the pathological changes were observed by HE staining. Results
      Compared with the normal control group, the OVA asthma group showed thickened
      alveolar septum, enlarged alveolar cavity and more obvious inflammatory cell
      infiltration, as well as significantly increased white blood cells associated
      with inflammatory response in the BALF. Whereas, compared with the OVA asthma
      group, the above mentioned changes in 15 mg/mL PM2.5 treated OVA asthma group
      were extremely obvious. ELISA showed that the levels of IFN-gamma and IL-10 in
      the serum of the OVA asthma group were significantly lower than those in the
      control group, while IL-17 significantly increased. Compared with the OVA asthma
      group, the levels of IFN-gamma and IL-10 in 15 mg/mL PM2-treated OVA asthma group
      significantly decreased, while the content of IL-17 significantly increased. Real
      time quantitative PCR showed that the expressions of TLR4 and NF-kappaB in PBMCs
      of the OVA asthma group were significantly higher than those in the control
      group. In 15 mg/mL PM2.5-treated OVA asthma group, the levels of TLR4 and NF
      kappaB increased significantly as compared with the OVA asthma group. Compared
      with the control group, the expressions of T-bet and FOXP3 proteins in the OVA
      asthma group were significantly lower than those in the control group, and the
      expression of RORgammat protein was significantly increased. Compared with the
      OVA asthma group, the levels of T-bet and FOXP3 proteins were reduced a lot in 15
      mg/mL PM2.5-treated OVA asthma group, while RORgammat protein level was
      remarkably elevated. Conclusion The 15 mg/mL PM2.5 can obviously promote OVA
      induced asthma and even lung injury by activating the TLR4/NF-kappaB signaling
      pathway.

PMID- 29169412
TI  - [TNF-alpha regulates the proliferation of human breast cancer cells via
      regulation of ceramide content].
AB  - Objective To determine whether tumor necrosis factor alpha (TNF-alpha) regulates
      the proliferation of MCF-7 and MDA-MB231 cells by modifying ceramide (Cer)
      production. Methods The optimum dosage and time of TNF-alpha treatment was
      determined at first. Immunocytochemistry combined with confocal microcopy was
      adopted to measure Cer content. MCF-7 and MDA-MB231 cells were treated with TNF
      alpha (50 ng/mL) alone or combined with the interference of ASM inhibitor,
      desipramine (Des) or sphingosine kinase 1 (SPHK1) inhibitor, dimethylsphingosine
      (DMS) to investigate the role of Cer in the proliferative regulation of TNF-alpha
      on breast cancer cells. MTT assay was used to determine the proliferation of the
      cancer cells and Western blotting was performed to measure the protein
      expressions of acid sphingomyelinase (ASM), SPHK1 and apoptosis or proliferation
      relevant factors including Bcl2, Bax and proliferating cell nuclear antigen
      (PCNA). Results TNF-alpha reduced the proliferation of MCF-7 cells, but enhanced
      the growth of MDA-MB-231 cells in a time- and dose-dependent manner. After TNF
      alpha treatment, the protein expression of ASM, but not SPHK1 increased in MCF-7
      cells, but both of them were elevated in MDA-MB-231 cells. Accordingly, Cer
      content was increase in MCF-7 cells treated by TNF-alpha, which was blocked by
      the pretreatment of ASM inhibitor Des. Cer content in MDA-MB231 cells was reduced
      by TNF-alpha, which was prevented by the pretreatment of SPHK1 inhibitor DMS. Des
      and DMS could respectively reverse the TNF-alpha-induced decrease and increase of
      proliferation in MCF-7 and MDA-MB-231 cells. Moreover, the protein expression of
      Bcl2 decreased and Bax increased in MCF-7 cells, and the protein expression of
      PCNA increased in MDA-MB231 cells after TNF-alpha treatment. Conclusion TNF-alpha
      can alter Cer production by regulating the expressions of ASM and SPHK1 to
      control the proliferation of MCF-7 and MDA- MB231 cells.

PMID- 29169413
TI  - [Notch1 signaling participates in the release of inflammatory mediators in mouse
      RAW264.7 cells via activating NF-kappaB pathway].
AB  - Objective To study the effect of Notch1 signaling on the release of inflammatory
      mediators in lipopolysaccharide (LPS)-induced macrophages and the related
      mechanism. Methods The expressions of Notch1 and hairy and enhancer of split 1
      (Hes1) mRNAs were investigated by reverse transcription PCR (RT-PCR) in mouse
      RAW264.7 cells after stimulated with 100 ng/mL LPS for 8 hours. Prior to
      stimulation with LPS, mouse RAW264.7 cells were treated with DAPT (10 MUmol/L),
      an inhibitor of Notch1 signaling, for 1 hour. The concentrations of tumor
      necrosis factor (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, nitric oxide
      (NO) and prostaglandin E2 (PGE2) in cell culture media were measured by ELISA.
      The mRNA levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were
      examined by RT-PCR. The protein levels of iNOS, COX-2, nuclear factor kappa Bp65
      (NF-kappaBp65) and phosphorylated nuclear factor kappaB inhibitor alpha (p
      IkappaBalpha) were detected by Western blotting. Results The expressions of
      Notch1 and Hes1 mRNAs significantly increased in mouse RAW264.7 cells after
      stimulated with LPS. The levels of TNF-alpha, IL-1beta, IL-6, NO and PGE2 were
      significantly up-regulated in cell culture media after stimulated with LPS, but
      the levels of those inflammatory mediators were reduced by DAPT. The mRNA and
      protein levels of iNOS and COX-2 were significant raised in mouse RAW264.7 cells
      after stimulated with LPS, while they were inhibited by DAPT. Both IkappaBalpha
      phosphorylation and NF-kappaBp65 translocation into nuclear in LPS-induced
      RAW264.7 cells were also inhibited by DAPT. Conclusion Notch1 signaling activates
      NF-kappaB to participate in LPS-induced inflammatory mediator release in
      macrophages.

PMID- 29169414
TI  - [Over-expressed Bax inhibitor 1 (BI-1) inhibits apoptosis of hippocampal neurons
      via endoplasmic reticulum IRE1-JNK pathway in rats with subarachnoid hemorrhage].
AB  - Objective To investigate the protective effect of lentivirus-mediated BI-1
      overexpression on hippocampal neurons in rats with subarachnoid hemorrhage (SAH)
      and the relationship with endoplasmic reticulum IRE1-JNK signaling pathway.
      Methods The lentivirus solution of BI-1 over-expression was injected into the
      brain of rats 24 hours before SAH rat model was established by intravascular
      puncture method. At 24 hours after modeling, the brain water content and
      neurological score of the rats were measured. The apoptosis of hippocampal
      neurons was detected by TUNEL assay. Western blotting was used to detect the
      expressions of BI-1 protein and endoplasmic reticulum stress (ERS) marker
      proteins GRP78 and IRE1. ERS in hippocampal neurons of the rats with SAH was
      intervened by IRE1alpha-specific inhibitor KIRA6, and then the protein
      expressions of p-IRE1, p-JNK, Bax, Bcl2 and caspase-3 were detected by Western
      blotting. Results BI-1 over-expression improved neurobehavioral score, decreased
      brain water content and hippocampal neuron apoptosis rate, and also down
      regulated GRP78 and IRE1 protein levels in the rats with SAH. Both the
      interference of KIRA6 and the over-expression of BI-1 inhibited the expressions
      of p-IRE1, p-JNK, Bax and caspase-3, and promoted the expression of anti
      apoptotic protein Bcl2. Conclusion Over-expression of BI-1 can inhibit the
      apoptosis of hippocampal neurons in rats with SAH by inhibiting the activation of
      ERS-mediated IRE1-JNK signaling pathway, thus ultimately attenuating the early
      brain injury following SAH.

PMID- 29169415
TI  - [Over-expression of thioredoxin-interacting protein promotes apoptosis of MIN6
      cells via activating p38MAPK pathway].
AB  - Objective To investigate the effect of thioredoxin interacting protein (TXNIP)
      over-expression on the apoptosis of MIN6 beta-cells and the mechanism involved.
      Methods Lentivirus carrying TXNIP gene was used to infect MIN6 beta-cells in
      logarithmic growth phase, and the infection efficiency was evaluated by
      fluorescence microscope and Western blotting. Then MIN6 beta-cells were divided
      into three groups: control group, empty lentivirus vector (LV-GFP) group and
      TXNIP over-expression (LV-GFP-TXNIP) group. CCK-8 assay was used to detect cell
      proliferation. AnnexinV-FITC/PI double staining was utilized to measure the
      apoptosis of MIN6 cells. Western blotting was applied to detect the expressions
      of TXNIP protein, TRX, Bax, Bcl2, cleaved caspase-3 (c-caspase-3), p38 mitogen
      activated protein kinase (p38MAPK), phospho-p38MAPK (p-p38MAPK) proteins in the
      MIN6 beta-cells before and after treated with p38MAPK inhibitor SP169316. Results
      At 72 hours after the infection, the infection rate reached (87.10+/-2.30)% and
      (92.21+/-0.54)% in LV-GFP group and LV-GFP-TXNIP group, respectively, suggesting
      that lentivirus-mediated TXNIP over-expression was desirable. Compared with
      control group and LV-GFP group, the cell viability markedly decreased, and cell
      apoptosis, Bax/Bcl2 ratio, expression of c-caspased-3 and p38MAPK phosphorylation
      significantly increased in LV-GFP-TXNIP group. However, both the Bax/Bcl2 ratio
      and c-caspase-3 protein expression in LV-GFP-TXNIP group were obviously reduced
      after treated with p38MAPK inhibitor. Conclusion TXNIP over-expression might
      promote the apoptosis of MIN6 cells via activating the p38 MAPK pathway.

PMID- 29169416
TI  - [Decursin reduces reactive oxygen species and inhibits cisplatin-induced
      apoptosis in rat renal tubular epithelial cells].
AB  - Objective To study the mechanism underlying the inhibitory effect of decursin on
      the apoptosis of rat renal tubular epithelial cells NRK-52E induced by cisplatin.
      Methods First, CCK-8 assay was used to detect the effects of 0, 10, 20, 40, 80,
      100, 150, 200 MUmol/L decursin and 0, 5, 10, 20, 30, 40, 50 MUg/mL cispatin
      treatment for 24 hours on cell proliferation in NRK-52E cells via determining the
      half inhibitory concentration (IC50). Then, NRK-52E cells were stimulated with 20
      MUg/mL cisplatin combined with 10, 50, 100 MUmol/L decursin, and cell activity
      was detected by CCK-8 assay. The cells were divided into normal control group, 20
      MUg/mL cisplatin stimulation group, and 10, 50, 100 MUmol/L decursin treated
      groups. Cell morphological changes was observed under inverted microscope,
      morphological changes of nucleus was detected by DAPI staining, cell apoptosis
      was detected by flow cytometry, the level of intracellular ROS was detected by
      DCFH-DA staining, and the apoptosis marker proteins cleaved-caspase-3 and cleaved
      PARP were examined by Western blot analysis. Results Compared with the normal
      control group, cisplatin significantly inhibited the activity of the cells, and
      IC50 was about 20 MUg/mL; compared with the model group, in the decursin
      pretreatment groups, the level of intracellular ROS decreased remarkably, the
      expressions of cleaved-casspase-3 and cleaved-PARP proteins were reduced, and
      cell apoptosis was depressed. Conclusion Decursin can decrease the intracellular
      ROS level and inhibit the apoptosis of NRK-52E cells induced by cisplatin.

PMID- 29169417
TI  - [Overexpression of PPENK reduces myocardial ischemia reperfusion injury by
      promoting mitophagy in rats].
AB  - Objective To investigate the effect of preproenkephalin-minimalistic
      immunologically defined gene expression-nuclear localization signal (PPENK-MIDGE
      NLS) vector postconditioning on mitophagy during myocardial ischemia reperfusion
      in rats. Methods Forty male SD rats were randomly divided into 4 groups: sham
      operation group, ischemia reperfusion group, PPENK-MIDGE-NLS group and Control
      MIDGE-NLS group. Myocardial ischemia reperfusion injury model was induced by
      ligating left anterior descending branch of coronary artery (LAD). Sham operation
      group was treated identically with the ischemia reperfusion group except that LAD
      was not tied and occluded. Ischemia reperfusion group, PPENK-MIDGE-NLS group, and
      Control-MIDGE-NLS group were treated with ligation and occlusion of LAD for 30
      minutes followed by 24 hour-reperfusion, with 1.5 mL saline, or 1.5 mL PPENK
      MIDGE-NLS vectors (200 MUg), or 1.5 mL Control-MIDGE-NLS vectors (200 MUg)
      administered respectively right before reperfusion started. Serum cTnI was
      assayed by ELISA and myocardial infarct size was measured by TTC. Ultrastructural
      changes of mitochondria and mitophagy were observed using electron microscope,
      and mitochondrial damage scores were analyzed. Expressions of the mitophagy
      related proteins such as PINK1, parkin, p62, TOM20 and LC3B were measured by
      Western blotting. Results Compared with the ischemia reperfusion group, both
      serum cTnI content and myocardial infarct size in the PPENK group decreased; the
      expression of PINK1, parkin, p62 and LC3B were all up-regulated. Mitophagy was
      enhanced and mitochondrial damages were alleviated, with conspicuous improvement
      in mitochondria ultrastructure. Conclusion PPENK-MIDGE-NLS vector
      postconditioning can mitigate myocardial ischemia reperfusion injury by promoting
      mitophagy in rats.

PMID- 29169418
TI  - [Mechanism underlying inhibition of proliferation and promotion of apoptosis by
      lapatinib in HL60 cells].
AB  - Objective To investigate the effect of lapatinib on cell proliferation and
      apoptosis in acute myeloid leukemia HL60 cells in vitro and the related molecular
      mechanisms. Methods The HL60 cells were treated with 5, 10, 15 MUmol/L lapatinib
      for 24 hours, and then morphological changes of the cells were observed under
      optical microscope. CCK-8 assay was used to assess the cell viability. Colony
      formation assay was performed to detect the cell proliferation ability. Cell
      apoptosis labeled by annexinV-FITC/PI were analyzed by flow cytometry. Wright
      modified LIU's staining and Hoechst33342 fluorescent staining were used to
      observe the morphology of the nucleus. Western blotting was utilized to detect
      the expressions of Bax, Bcl2, caspase-3, caspase-9, cleaved caspase-3, cleaved
      caspase-9, cleaved poly-ADP-ribose polymerase (cleaved PARP), cell proliferation
      regulating inhibitor of protein phosphatase 2A (CIP2A), c-MYC, AKT and p-AKT.
      Results Compared with the control group, lapatinib inhibited cell proliferation
      and promoted apoptosis, induced nuclear fragmentation, chromatin condensation of
      HL60 cells in a dose-dependent manner. Meanwhile, it down-regulated the
      expression of Bcl2, up-regulated the levels of Bax, cleaved caspase-3, cleaved
      caspase-9 and cleaved PARP, and decreased the levels of CIP2A, p-AKT and c-MYC.
      Conclusion Lapatinib could inhibit cell proliferation and promote apoptosis in
      HL60 cells by inhibiting the CIP2A/AKT/c-MYC signal pathway.

PMID- 29169419
TI  - [Aspirin inhibits the proliferation of breast cancer cells via inducing apoptosis
      and autophagy].
AB  - Objective To explore the effect of aspirin on the apoptosis and autophagy of
      human epidermal growth factor receptor 2 (HER2)-positive AU-565 breast cancer
      cells and triple negative MDA-MB-231 breast cancer cells. Methods MTT assay was
      performed to detect the effect of aspirin on cell proliferation of cancer cells;
      flow cytometry was performed to assess the effect of aspirin on cell apoptosis;
      Western blotting was used to determine the protein expressions of apoptosis
      related proteins Bcl2, cleaved caspase-3 (c-caspase-3), cleaved PARP (c-PARP) and
      autophagy-related gene 3 (ATG3), LC3A, LC3B. Results Aspirin inhibited the
      proliferation of AU-565 and MDA-MB-231 cells and increased the cell apoptosis.
      The expressions of c-caspase-3 and c-PARP were up-regulated, the Bcl2 was down
      regulated, and ATG3, LC3A, LC3B were also significantly up-regulated. Conclusion
      Aspirin can inhibit the proliferation of AU-565 and MDA-MB-231 breast cancer
      cells via inducing cell apoptosis and autophagy.

PMID- 29169420
TI  - [Knockdown of AKT1 gene enhances the sensitivity of gastric cancer xenografts of
      nude mice to doxorubicin].
AB  - Objective To investigate the effect of lentivirus-mediated shRNA targeting AKT1
      gene on the sensitivity of gastric cancer xenografts to doxorubicin. Methods To
      establish the lentiviral vector of AKT1 RNA interference (RNAi), the vector of
      pGCSIL-shAKT1-GFP was infected into HEK293T cells, and meanwhile, the empty
      vector pGCSIL-shCON-GFP was assigned as a blank group, and then the viruses were
      harvested. BGC-823 gastric cancer cells were infected with the viruses. The
      protein expression of AKT1 was detected by Western blotting. The gastric cancer
      xenografts in nude mice were constructed using BGC-823 cells infected with the
      viruses, followed by the administration of doxorubicin. The size of tumor was
      evaluated and the growth curve of the tumor was drawn; HE staining was used to
      observe the pathological conditions of the xenografts; and the apoptosis of
      xenografts was examined by TUNEL assay. Results The recombinant plasmid of LV
      shAKT1 was successfully constructed, and then transfected into HEK293T cells to
      produce high-titer lentivirus with a titer of 5*108 TU/mL. The expression of AKT1
      protein in gastric cancer BGC-823 cells was significantly down-regulated after
      successfully infected with the LV-shAKT1. Nude mice xenografts experiment showed
      that AKT1 gene silencing inhibited the growth of tumor xenografts, and also
      enhanced the inhibitory effect of doxorubicin on the growth of tumor xenografts.
      TUNEL staining showed that AKT1 gene silencing promoted the apoptosis of tumor
      xenograft cells, and the effect was more obvious when combined with doxorubicin.
      Conclusion AKT1 gene silencing can enhance the sensitivity of gastric cancer
      xenografts to doxorubicin through promoting cell apoptosis.

PMID- 29169421
TI  - [miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by
      interfering with the Rb/E2F signaling pathway].
AB  - Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of
      T24 and EJ bladder cancer cells, and explore the possible molecular mechanism.
      Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells.
      The target gene of miR-503-5p was predicted by bioinformatics. The expressions of
      E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were
      detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F
      signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by
      Western blotting. The cell cycle of bladder cancer cell lines was determined by
      flow cytometry. MTT assay and plate cloning assay were performed to observe the
      proliferation ability of bladder cancer cells. Results After miR-503-5p mimics
      transfection, the expression of miR-503-5p in bladder cancer cells significantly
      increased. The increased expression of miR-503-5p significantly reduced the
      expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer
      cells. What's more, the expressions of Rb/E2F signal pathway proteins were down
      regulated. The bladder cancer cells were arrested in G0/G1 phase, and their
      growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over
      expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down
      regulating the expression of the Rb/E2F signaling pathway.

PMID- 29169422
TI  - [miR-125b suppresses the aerobic glycolysis of osteosarcoma HOS cells by
      downregulating the expression of hexokinase-2].
AB  - Objective To investigate the effect of miR-125b on the aerobic glycolysis of
      osteosarcoma HOS cells and its underlying mechanism. Methods Real-time
      quantitative PCR was performed to detect the expression of miR-125b in HOSB
      normal human osteoblast cells and HOS osteosarcoma cells. The glucose uptake rate
      was assessed with 3H-2 deoxyglucose (3H-2DG) and lactate production was tested
      with the kits to observe the effect of miR-125b-mimics on the aerobic glycolysis
      of osteosarcoma HOS cells. Hexokinase-2 (HK2) protein was detected by Western
      blot analysis. Dual luciferase reporter gene assay was used to determine whether
      HK2 was the direct target of miR-125b. Results Compared with HOSB normal human
      osteoblast cells, the expression of miR-125b was significantly lower in HOS
      cells. The glucose uptake and lactate production were downregulated in HOS cells
      transfected with miR-125b-mimics. Aerobic glycolysis of HOS cells was markedly
      inhibited. Protein level of HK2 was significantly inhibited in HOS cells
      transfected with miR-125b-mimics. Luciferase assay indicated that HK2 was the
      direct target of miR-125b. Conclusion miR-125b is down-regulated in HOS cells,
      and it inhibits the aerobic glycolysis of HOS cells by directly regulating the
      expression of HK2.

PMID- 29169423
TI  - [Isolation and identification of extracellular vesicles from rat bone marrow
      mesenchymal stem cells].
AB  - Objective To investigate the isolation and identification of extracellular
      vesicles (EVs) from rat bone marrow mesenchymal stem cells (BMSCs) and the effect
      of -80DegreesCelsius cryopreservation on the structural integrity of the EVs'
      membrane. Methods EVs were isolated and purified from the culture supernatant of
      bone marrow mesenchymal stem cells (BMSC-CS) by ultrahigh velocity
      centrifugation. The size and morphology of EVs were observed by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). Western blotting was
      performed to detect the expression of CD63 protein. The integrity of the EVs'
      membrane structure was observed by TEM at different time after storage at 
      80DegreesCelsius. Results SEM showed that a large number of EVs with membrane
      structures, round or oval and ranged in size from 50 to 1000 nm were attached
      onto BMSC surface. Under TEM, BMSC-EVs were similar in morphology and size to
      them under SEM. Western blotting revealed that BMSC-EV expressed the marker
      protein CD63. BMSC-EVs had a complete membrane structure at the first month and
      the third month, whereas BMSC-EV's membrane structure ruptured at the sixth month
      after storage at -80DegreesCelsius. Conclusion BMSC-EVs is successfully
      extracted, and the membrane structure integrity get worse with the prolongation
      of cryopreservation time.

PMID- 29169424
TI  - [Sodium hydrosulfide attenuates myocardial injury through activating thioredoxin
      system in diabetic rats].
AB  - Objective To investigate the effect of exogenous hydrogen sulfide from sodium
      hydrosulfide (NaHS) on cardiac thioredoxin (Trx) system in diabetic rats. Methods
      Male Sprague-Dawley rats were randomly divided into a normal group, a diabetic
      group, and three NaHS (14, 28 and 56 MUmol/kg) treatment groups, with 6 rats in
      each group. Type 1 diabetes was induced in the groups by a single intraperitoneal
      (i.p.) injection of streptozotocin. At the fifth week after modeling, the NaHS
      treatment groups were injected (i.p.) with NaHS at the doses of 14, 28 and 56
      MUmol/kg once a day, respectively. After the treatment for 4 weeks, the fasting
      blood glucose (FBG) level and ventricular hemodynamic parameters were measured.
      The changes of myocardial pathomorphology were observed by HE staining. The
      ultrastructural changes of cardiomyocytes were observed by transmission electron
      microscopy. The levels of serum lactate dehydrogenase (LDH), creatine kinase
      (CK), and creatine kinase MB isozyme (CK-MB) were examined using the kits. Serum
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were
      assayed by ELISA. The levels of total antioxidant capacity (T-AOC), lipid
      peroxide (LPO), and malondialdehyde (MDA) in myocardium were analyzed using the
      kits. The mRNA expression of heme oxygenase 1 (HO-1) was detected using reverse
      transcription PCR (RT-PCR). The expression levels of Trx, Trx-interacting protein
      (TXNIP), and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) in
      myocardium were measured using Western blotting. Results Compared with the normal
      group, the left ventricular systolic and diastolic functions were weakened in the
      diabetic group, and the myocardial morphological structure and ultrastructure
      were damaged obviously. The FBG, LDH, CK, CK-MB, IL-1beta, IL-6, TNF-alpha, LPO
      and MDA levels increased, while the T-AOC level decreased. The myocardial Trx
      protein expression was reduced, while the expressions of HO-1 mRNA, TXNIP and
      NOX2 proteins were elevated in the diabetic group. Compared with the diabetic
      group, the left ventricular systolic and diastolic functions, myocardial
      morphological structure and ultrastructure were improved in the three NaHS
      treatment groups. The LDH, CK, CK-MB, IL-1beta, IL-6, TNF-alpha, LPO and MDA
      levels decreased, while T-AOC increased. The myocardial HO-1 mRNA and Trx protein
      expressions were enhanced, while TXNIP and NOX2 protein expressions were
      suppressed. Conclusion NaHS treatment attenuates diabetic myocardial injury, and
      the mechanisms may be associated with the activation of the Trx system, the
      enhancement of antioxidant capability and the inhibition of inflammatory factor
      release.

PMID- 29169425
TI  - [Establishment of Acinetobacter baumannii-induced pneumonia model in mice].
AB  - Objective To establish Acinetobacter baumannii (A. baumannii)-induced pneumonia
      models in C57BL/6 mice, and study the molecule mechanism of A. baumannii
      infection. Methods Eighty C57BL/6 mice were divided into normal control group,
      cyclophosphamide-treated group, A. baumannii infection group, and
      cyclophosphamide-pretreated A. baumannii infection group. Immunodeficient mice
      were prepared by injecting cyclophosphamide intraperitoneally. A. baumannii was
      isolated from intensive care unit (ICU) and fresh bacteria (1*108 CFU/mL) were
      prepared. Each normal or immunodeficient mouse was inoculated with 50 MUL A.
      baumannii through trachea. The lung, bronchoalveolar lavage fluid (BALF) and
      blood were collected at 6, 24 and 72 hours after inoculation. The numbers of
      white blood cells (WBCs) and neutrophils were detected by cell counting. The
      histopathology of the lung was evaluated by HE staining. Cytokines such as
      granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN
      gamma), interleukin 1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor
      necrosis factor alpha (TNF-alpha) were detected by ELISA. Results A. baumannii
      was eliminated within 72 hours after infection in normal mice, whereas the
      bacteria continued to replicate rapidly in the lungs and blood in the
      immunodeficient mice. The numbers of WBCs and neutrophils were elevated markedly
      6 hours post infection, and return to the normal within 72 hours. However, the
      numbers of WBCs and neutrophils continuously increased in cyclophosphamide
      pretreated A. baumannii infection group, and the pulmonary inflammatory was more
      severe than that in the normal mice. The cytokines of blood increased markedly 6
      hours post infection, and then decreased until 72 hours. However, the cytokines
      continuously increased in cyclophosphamide-pretreated A. baumannii infection
      group. Conclusion A. baumannii-induced pneumonia models in C57BL/6 mice were
      established successfully.

PMID- 29169426
TI  - [Knockdown of Alox5 gene promotes apoptosis of K562/ADM cells].
AB  - Objective To investigate the effect of short hairpin RNA (shRNA) knockdown of
      arachidonate 5-lipoxygenase (Alox5) gene on the apoptosis of resistant chronic
      myeloid leukemia K562/ADM cells. Methods Three pairs of shRNA fragment targeting
      human Alox5 gene were synthesized and inserted into pGenesil-1 interference
      vector. Enzyme digestion and sequencing were performed to identify the
      recombinant plasmid pGenesil-1-shRNA-Alox5. The plasmid was then transfected into
      K562/ADM cells. Real-time quantitative PCR and Western blotting were used to
      detect the Alox5 mRNA and protein levels to get the best interference group. The
      pGenesil-1-shRNA-Alox5 plasmid group with higher interference efficiency was
      selected as the experimental subjects. Real-time quantitative PCR was adopted to
      detect the expression level of bcr/abl mRNA and Western blotting to detect the
      BCR/ABL fusion protein, and the apoptotic rate was assessed by flow cytometry.
      Results The enzyme digestion and sequencing confirmed the successful construction
      of recombinant plasmid. Compared with the negative pGenesil-1-K562/ADM control
      group and blank K562/ADM cell group, the Alox5 mRNA and protein levels of
      K562/ADM cells transfected with pGenesil-1-shRNA-Alox5 recombinant plasmid
      significantly decreased, and after the knockdown of Alox5, the levels of bcr/abl
      mRNA and BCR/ABL fusion protein significantly decreased and the apoptosis rate
      increased obviously. Conclusion The knockdown of Alox5 gene can induce the
      decreased levels of bcl/abl mRNA and BCR/ABL fusion protein in the K562/ADM cells
      and increased apoptosis rate.

PMID- 29169427
TI  - [Single nucleotide polymorphism of IL-23 receptor gene is associated with
      susceptibility to recurrent oral ulceration].
AB  - Objective To explore whether single nucleotide polymorphism (SNP) in interleukin
      23 receptor (IL-23R) gene is associated with the susceptibility to recurrent oral
      ulceration (ROU). Methods The genotype of SNP rs11465817 and rs1343152 was
      determined by MALDI-TOF-MS in 42 ROU patients and 86 age- and sex-matched healthy
      controls. The genotype and allele frequencies were analyzed by Chi-square test in
      both groups. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated
      to analyze the associations between the susceptibility of ROU and the genotypes.
      Results The rs1343152 allele and genotype frequency distribution had no
      significantly difference between the case group and the control group. Compared
      with the control group, rs11465817 allele and genotype frequency distribution in
      the ROU group had significant difference (OR=2.715, 95%CI=1.543-4.777). The AA+AC
      genotype increased the risk of ROU occurrence by 2.44 times. Conclusion IL-23R
      rs11465817 contributes to the risk of ROU in Chinese.

PMID- 29169428
TI  - [Associations of interleukin gene IL1B-511C/T and IL1RN+8006T/C polymorphisms
      with coronary artery disease in Chinese population: meta-analysis].
AB  - Objective To explore the relationships between the IL1B-511C/T and IL1RN+8006T/C
      polymorphisms and coronary heart disease (CHD) in Chinese population. Methods We
      analyzed case-control studies regarding the associations of the IL1B-511C/T and
      IL1RN+8006T/C polymorphisms with CHD in Chinese population by searching PubMed,
      EMBASE, VIP Database, Wanfang and China National Knowledge Infrastructure
      databases. All articles were rigorously evaluated and screened based on the
      inclusion and exclusion criteria. Meta-analysis was performed using Review
      Manager 5.3 software. Results Eight case-control studies with a total of 1460 CHD
      patients and 1547 control subjects met the inclusion criteria. The pooled results
      from IL1B-511C/T polymorphism showed increased risk in allelic model (OR=1.17,
      95%CI=1.04-1.31), recessive model (OR=1.58, 95%CI=1.32-1.90) and homozygote model
      (OR=1.38, 95%CI=1.09-1.74). But for IL1RN+8006T/C polymorphism, decreased risk
      was observed in allelic model (OR=0.55, 95%CI=0.43-0.69), dominant model
      (OR=0.52, 95%CI=0.40-0.66) and heterozygote model (OR=0.51, 95%CI=0.40-0.66).
      Conclusion The IL1RN+8006T/C polymorphism may play a protective role in CHD. The
      IL1B-511C/T polymorphism is found to be associated with a significant increased
      risk for CHD based on our analysis.

PMID- 29169429
TI  - [Preparation and application of polyclonal antibody against non-structural
      protein 1 (NS1) of duck Tembusu virus].
AB  - Objective To express prokaryotically the non-structural protein 1 (NS1) of duck
      Tembusu virus (DTMUV) and prepare NS1-specific polyclonal antibodies. Methods The
      NS1 gene of DTMUV strain AH-F10 was amplified by PCR, followed by subcloning and
      expression in the prokaryotic vector pET-32a. The recombinant NS1 protein was
      successfully expressed in Escherichia coli BL21 (DE3), and purified with
      hydroxymethyl urea and renatured by gradient centrifugation. The BALB/c mice were
      immunized with the purified recombinant NS1 protein to prepare polyclonal
      antibodies against the NS1 protein. Furthermore, the titer of the polyclonal
      antibodies was determined by agar diffusion test (AGP), and the specificity of
      the polyclonal antibodies was verified by Western blotting and indirect
      immunofluorescence assay (IFA). Results Polyclonal antibodies against NS1 protein
      in serum was successfully obtained with an AGP titer of 1:8. Western blotting and
      IFA demonstrated that the serum with polyclonal antibodies had a high-level
      specificity and reactivity to the NS1 protein of DTMUV. Conclusion Polyclonal
      antibodies against DTMUV NS1 protein were successfully prepared and validated in
      this study.

PMID- 29169430
TI  - Spontaneous Pneumothorax.
AB  - BACKGROUND: Few reliable data are available on the epidemiology and treatment of
      spontaneous pneumothorax. We studied the sex and age distribution, frequency of
      hospitalization, mortality, and conservative versus surgical care of this
      condition in Germany in order to draw well-founded conclusions about its in
      hospital diagnosis and treatment. METHODS: Data from all patients aged 10 or
      older who were hospitalized in the period 2011-2015 with a main discharge
      diagnosis of pneumothorax of neither traumatic nor iatrogenic origin were
      retrieved from the German Federal Statistical Office. Because of their source,
      all data were based on case numbers rather than patient numbers. RESULTS: During
      the period of the study, there were 52 738 admissions with the main diagnosis of
      spontaneous pneumothorax, corresponding to an annual frequency of hospitalization
      of 14.3 per 100 000 persons per year (95% confidence interval, 14.0 to 14.5). Men
      were more frequently affected than women. The lethality and in-hospital mortality
      of this condition (<= 0.08% and <= 0.3%, respectively) were low among persons
      aged 15 to 45, but markedly higher in persons over age 90 (9.4% and 15.9%,
      respectively). The frequency of accompanying pulmonary diagnoses also rose with
      age. Computerized tomography (CT) was performed in 38.9-54.6% of
      hospitalizations, depending on age. Monitoring on an intensive care unit was
      carried out in 36% of cases. More than one-quarter of cases involved surgical
      treatment. CONCLUSION: The danger to life and the likelihood of an accompanying
      pulmonary diagnosis are both low up to age 45. Treatment on an intensive care
      unit and computerized tomography of the chest should be performed only for strict
      indications in patients under age 45. The pathophysiological basis of the
      differing patterns of illness depending on age and sex requires further
      investigation.

PMID- 29169432
TI  - Consider the Risk of Goiter.

PMID- 29169431
TI  - Monoclonal IgM Gammopathy and Waldenstrom's Macroglobulinemia.
AB  - BACKGROUND: 3.2-3.5% of persons over age 50 have a monoclonal gammopathy.
      Monoclonal gammopathies have many causes, including cancer. 10-20% of monoclonal
      gammopathies are of isotype IgM. A systematic approach to the differential
      diagnosis of IgM gammopathies is essential because of the different therapeutic
      implications of the various underlying conditions. METHODS: This review is based
      on pertinent publications retrieved by a selective search in PubMed and current
      guidelines from Germany and abroad. RESULTS: The diagnosis of a monoclonal IgM
      gammopathy is established by serum electrophoresis in combination with immune
      fixation. Further evaluation enables the identification of the underlying
      condition: the differential diagnosis includes IgM-MGUS (monoclonal gammopathy of
      unclear significance), Waldenstrom's disease, and IgM myeloma. The therapeutic
      implications of the under - lying condition vary from watchful waiting in IgM
      MGUS to combined rituximab and antineoplastic chemotherapy (off-label first-line
      use of rituximab) in symptomatic Waldenstrom's macroglobulinemia. Ibrutinib has
      been approved for the treatment of patients with recurrences, or of those for
      whom first-line treatment with rituximab and chemotherapy is not suitable. The
      current treatment options do not result in cure. In symptomatic Waldenstrom's
      disease, the goal of treatment is to keep the disease under control for as long
      as possible without impairing the patient's quality of life. CONCLUSION: Evidence
      based treatment decisions in Waldenstrom's macroglobulinemia now rely mainly on
      small-scale, single-armed trials. Patients with this disease should be treated in
      the setting of a clinical trial if possible. Trials aimed at improving the
      quality of treatment for other IgM-associated diseases, such as IgM neuropathies
      and cold agglutinin disease, would also be desirable.

PMID- 29169433
TI  - In Reply.

PMID- 29169434
TI  - Additional Comments.

PMID- 29169435
TI  - Paying Attention to Electrolytes.

PMID- 29169436
TI  - In Reply.

PMID- 29169437
TI  - Oriental Sore (Old-World Cutaneous Leishmaniasis).

PMID- 29169438
TI  - Separate Septic and Aseptic Operating Areas.

PMID- 29169439
TI  - In Reply.

PMID- 29169440
TI  - Multiple Pulmonary Emboli of Bone Cement after Kyphoplasty.

PMID- 29169441
TI  - Patient Selection and Counseling for Urinary Diversion.
AB  - Patient selection and preoperative counseling are critical aspects of determining
      which urinary diversion to perform and should be emphasized at each stage of
      preoperative planning. The surgeon must have a thorough understanding of the
      patient's disease process, functional and psycho-emotional status, and social
      support network so that they can set appropriate expectations. It is also crucial
      to have a multidisciplinary team of individuals who are experienced with all
      aspects of urinary diversion care, including ostomy nurses, nurse navigators, and
      urologic surgeons skilled at teaching and trouble-shooting self-catheterization
      for continent cutaneous diversion and orthotopic diversion in the setting of
      hypercontinence.

PMID- 29169442
TI  - Quality of Life and Urinary Diversion.
AB  - Health-related quality-of-life outcomes after urinary diversion vary
      significantly. Preserving and even improving health-related quality of life are
      highly relevant to urinary diversion. Life after urinary diversion is
      fundamentally different than before.

PMID- 29169443
TI  - Perioperative Preparation and Nutritional Considerations for Patients Undergoing
      Urinary Diversion.
AB  - Patients undergoing urinary diversion are at high risk for complications in the
      perioperative period. The exact cause of these complications remains poorly
      defined but is likely multifactorial. Current efforts to optimize patients in the
      perioperative period, including prehabilitation, smoking cessation, recognition
      and treatment of comorbid conditions and malnutrition, immunonutrition
      supplementation, carbohydrate loading, and prevention of known complications and
      implementation of enhanced recovery after surgery pathways, seem beneficial in
      helping to improve outcomes in this at-risk population. Further studies (some of
      which are ongoing) are necessary to help optimize these strategies and identify
      which modifiable factors have the greatest impact.

PMID- 29169444
TI  - Urinary Diversion in Renal Transplantation.
AB  - Renal transplantation involving anatomically or functionally altered recipient
      urinary reservoirs is a challenging procedure. Initial reports discouraged kidney
      transplantation in patients with urinary diversion due to inferior outcomes.
      However, more recent studies have shown that although there are more infectious
      complications, patients with urinary diversions have comparable long-term graft
      survival with those with native anatomy. Careful preoperative assessment of these
      candidates is mandatory. Unique technical and surgical concepts must be
      considered before embarking on transplanting this specific cohort of kidney
      transplantation candidates.

PMID- 29169445
TI  - Advances in Pediatric Urinary Diversion.
AB  - Pediatric urinary diversion is performed for a unique set of indications with
      many options to consider. Although surgical intervention has decreased in
      necessity overall due to advances in expectant management, it remains an
      important tool. There are many options and various factors to consider in
      choosing the right type of diversion for an individual and these patients require
      lifelong follow-up with a pediatric urologist and eventually an adult urologist.
      This article provides a detailed review of the most relevant techniques used by
      pediatric urologists for urinary diversion.

PMID- 29169446
TI  - Tissue Engineering and Conduit Substitution.
AB  - Radical cystectomy (RC) with urinary diversion is associated with significant
      morbidity, much of which arises from the interposition of bowel segments in the
      urinary system. A tissue-engineered alternative for urinary diversion could
      dramatically reduce the perioperative and long-term morbidity associated with RC.
      Attempts at developing a tissue-engineered incontinent urinary conduit (TEUC)
      have involved mechanical scaffolds and promoting tissue growth within them.
      Despite some preclinical success, significant obstacles remain before a TEUC is
      ready for clinical use. A further understanding of tissue and materials
      engineering may help overcome these obstacles or help to develop a new approach
      to tissue engineering entirely.

PMID- 29169447
TI  - Metabolic and Nutritional Consequences of Urinary Diversion Using Intestinal
      Segments to Reconstruct the Urinary Tract.
AB  - Intestinal segments in various forms have been used to reconstruct the urinary
      tract since the mid-1800s. Currently, many different forms of continent and
      incontinent diversion options exist. Incorporating bowel mucosa within the
      urinary tract leads to predictable metabolic and nutritional consequences. The
      use of ileum or colon can cause a hyperchloremic metabolic acidosis, vitamin B12
      deficiency, osteoporosis, fat malabsorption, urinary calculi, and ammoniagenic
      encephalopathy. Due to metabolic and nutritional consequences associated with the
      use of jejunum and gastric segments, the use of these bowel segments is not
      recommended.

PMID- 29169448
TI  - Conduit Urinary Diversion.
AB  - This review summarizes the salient aspects of the ileal conduit with 3
      pedagogical objectives in mind: (1) to describe the surgical steps emphasizing
      important surgical principles, (2) to provide insight on various preoperative and
      postoperative considerations, and (3) to summarize the risks of the long-term
      complications and quality of life. We aim to inform a broad medical readership.

PMID- 29169449
TI  - Male Neobladder.
AB  - Successful outcome with orthotopic neobladders begins in the preoperative phase
      with appropriate patient selection and extensive patient counseling. Meticulous
      attention to surgical and oncological principles is required to optimize
      neobladder outcomes. Long-term follow-up is needed not only for oncological
      purposes but also to monitor for the late complications, such as
      ureterointestinal strictures, renal deterioration, infections, and voiding
      dysfunction.

PMID- 29169450
TI  - Orthotopic Urinary Diversion for Women.
AB  - Orthotopic neobladder is a viable option for women undergoing cystectomy for
      bladder cancer, with excellent oncologic outcomes and a low incidence of urethral
      recurrence. Careful patient selection is important, as is developing a clear
      understanding by the patient and her family in what to expect with an orthotopic
      diversion. Surgical technique is also important in optimizing functional
      outcomes, such as continence, sexual function, and decreased rate of vaginal
      fistula formation, and urinary retention.

PMID- 29169451
TI  - Continent Cutaneous Diversion.
AB  - Techniques in continent cutaneous urinary diversion (CCUD) have evolved
      significantly over the last 30 years resulting in several well-established
      procedures. CCUD is well suited for patients in whom the urethra cannot be used
      for orthotopic diversion due to preexisting incontinence, radiation damage, or
      malignancy. Reservoirs are constructed with adherence to basic principles of
      continent urinary diversion, including the use of detubularized bowel in a
      spherical conformation for pouch creation with either ileum or the right colon.
      The article reviews the history, patient selection, preoperative evaluation,
      surgical technique, and outcomes of CCUD.

PMID- 29169452
TI  - Robotic Cystectomy with Intracorporeal Urinary Diversion: Review of Current
      Techniques and Outcomes.
AB  - This article reviews the current techniques and outcomes of robot-assisted
      radical cystectomy with totally intracorporeal urinary diversion. Discussion
      includes techniques for port placement and methods for urinary diversion for
      neobladder, ileal conduit, and one case of continent cutaneous diversion. The
      outcomes analyzed include operative time, estimated blood loss, transfusion rate,
      conversion to open surgery, and early or late postoperative complications.

PMID- 29169453
TI  - Surgical Complications of Urinary Diversion.
AB  - Urinary diversion (UD) with an intestinal segment has significant risks of short-
      and long-term complications. With modern reporting criteria, understanding of the
      true prevalence and spectrum of these complications has improved. Methods to
      minimize early postoperative complications include enhanced recovery pathways,
      restricted intraoperative fluid protocols, and referral to high-volume centers.
      With long-term follow-up after UD, the risk of complications steadily rises. Late
      surgical complications include ureterointestinal anastomotic strictures,
      urolithiasis, and stomal issues. Patients with UDs require close surveillance to
      monitor for anatomic, infectious, and metabolic complications and surgeons who
      perform UD should be aware of the risk and timing of postoperative complications.

PMID- 29169454
TI  - Secondary Tumors After Urinary Diversion.
AB  - It has been known that urinary diversions juxtaposing the urinary and intestinal
      tracts lead to increased incidence of secondary malignancies. Although
      tumorigenesis in ureterosigmoidostomies follows the typical course from adenomas
      to adenocarcinomas, secondary malignancies arising from isolated intestinal
      diversions are much more heterogeneous. Research over the last half century has
      unveiled patterns of incidence and progression, while also uncovering possible
      mechanisms driving the neoplastic changes. In this review, we summarize the
      current understanding of these unique tumors, with the hope that the knowledge
      gained may shed light on the etiologies of other cancers arising from the urinary
      and intestinal tracts.

PMID- 29169455
TI  - Re-Creating the Urinary Tract: An Art Derived from Science.

PMID- 29169456
TI  - Urinary Diversion: Nutritional Evolution and Surgical Revolution.

PMID- 29169457
TI  - The Importance of Research Data Sharing: The Meeting Reports Section of the JID.

PMID- 29169458
TI  - Evidence that Human Skin Microbiome Dysbiosis Promotes Atopic Dermatitis.
AB  - Patients with atopic dermatitis are frequently colonized by Staphylococcus
      aureus. If S. aureus is present, then the subject tends to have more severe
      disease. However, it is unclear if S. aureus is a cause of atopic dermatitis or a
      consequence of the abnormal epithelial environment. In this issue of the Journal
      of Investigative Dermatology, Meylan et al. present evidence from a prospective
      clinical trial that shows that S. aureus colonization precedes onset of atopic
      dermatitis in children. These observations suggest that S. aureus may cause
      atopic dermatitis in some individuals.

PMID- 29169459
TI  - Production of Neoepitopes by Dynamic Structural Changes on BP180/Type XVII
      Collagen.
AB  - Linear IgA bullous dermatosis is characterized by IgA autoantibodies reactive
      with LAD-1 and LABD97, truncated forms of BP180 (type XVII collagen), but not
      with full-length BP180. Toyonaga et al. determined that cleavage within both the
      C-terminal region and NC16A domain plays a role in exposure of neoepitopes on the
      15th collagenous domain of BP180.

PMID- 29169460
TI  - Negative Regulation of Skin Pigmentation in Three-Dimensional Reconstructs by
      Adipose-Derived Mesenchymal Cells.
AB  - The regulation of site-specific pigmentation in reconstructs used for skin
      grafting is incompletely understood. Using an engineered skin equivalent model,
      Klar et al. incorporated adipose-derived mesenchymal cells into skin substitutes
      and found that adipose-derived mesenchymal cells secreted high levels of
      transforming growth factor-beta1, which down-regulates melanogenic enzymes such
      as tyrosinase to decrease melanin synthesis and prevent normal pigmentation of
      resulting skin grafts.

PMID- 29169461
TI  - Lymphatic versus Hematogenous Melanoma Metastases: Support for Biological
      Heterogeneity without Clear Clinical Application.
AB  - Melanoma demonstrates considerable biological heterogeneity and is associated
      with several routes of dissemination including lymphatic and hematogenous.
      Locoregional control via surgery may improve outcomes for patients with limited
      lymphatic metastases. Once stage IV disease is diagnosed, clinical outcomes are
      determined by molecular and/or immunologic factors and identification of
      tumor/microenvironmental features correlating with distant metastases is critical
      for future prognostic stratification.

PMID- 29169462
TI  - Skin-Derived Vitamin D3 Protects against Basal Cell Carcinoma.
AB  - UVR in sunlight causes mutations that drive basal cell carcinomas. However, the
      incidence of these tumors plateaus with prolonged exposure, but the incidence of
      other skin cancers increases. Makarova et al. now show that vitamin D3 produced
      in the skin by UVR protects against its oncogenic effects by inhibiting Hedgehog
      signaling, whereas dietary vitamin D3 does not.

PMID- 29169463
TI  - A MUSE for Skin Regeneration.
AB  - With a rise in the prevalence of chronic wounds and other soft tissue defects,
      there is an urgent need to regenerate skin. Multilineage-differentiating stress
      enduring cells were identified as distinct pluripotent stem cells in mesenchymal
      cell populations in humans. New research demonstrates the ability to effectively
      differentiate multilineage-differentiating stress-enduring cells into fibroblasts
      and keratinocytes for skin reconstitution.

PMID- 29169464
TI  - Erratum.

PMID- 29169465
TI  - Research Techniques Made Simple: Emerging Methods to Elucidate Protein
      Interactions through Spatial Proximity.
AB  - Interactions between proteins are essential for fundamental cellular processes,
      and the diversity of such interactions enables the vast variety of functions
      essential for life. A persistent goal in biological research is to develop assays
      that can faithfully capture different types of protein interactions to allow
      their study. A major step forward in this direction came with a family of methods
      that delineates spatial proximity of proteins as an indirect measure of protein
      protein interaction. A variety of enzyme- and DNA ligation-based methods measure
      protein co-localization in space, capturing novel interactions that were
      previously too transient or low affinity to be identified. Here we review some of
      the methods that have been successfully used to measure spatially proximal
      protein-protein interactions.

PMID- 29169466
TI  - SnapshotDx Quiz: December 2017.

PMID- 29169467
TI  - Cells to Surgery Quiz: December 2017.

PMID- 29169468
TI  - Renal Outcomes in Anticoagulated Patients With Atrial Fibrillation.
AB  - BACKGROUND: Lifelong oral anticoagulation, either with warfarin or a non-vitamin
      K antagonist oral anticoagulant (NOAC), is indicated for stroke prevention in
      most patients with atrial fibrillation (AF). Emerging evidence suggests that
      NOACs may be associated with better renal outcomes than warfarin. OBJECTIVES:
      This study aimed to compare 4 oral anticoagulant agents (apixaban, dabigatran,
      rivaroxaban, and warfarin) for their effects on 4 renal outcomes: >=30% decline
      in estimated glomerular filtration rate (eGFR), doubling of the serum creatinine
      level, acute kidney injury (AKI), and kidney failure. METHODS: Using a large U.S.
      administrative database linked to laboratory results, the authors identified
      9,769 patients with nonvalvular AF who started taking an oral anticoagulant agent
      between October 1, 2010 and April 30, 2016. Inverse probability of treatment
      weighting was used to balance more than 60 baseline characteristics among
      patients in the 4 drug cohorts. Cox proportional hazards regression was performed
      in the weighted population to compare oral anticoagulant agents. RESULTS: The
      cumulative risk at the end of 2 years for each outcome was 24.4%, 4.0%, 14.8%,
      and 1.7% for >=30% decline in eGFR, doubling of serum creatinine, AKI, and kidney
      failure, respectively. When the 3 NOACs were pooled, they were associated with
      reduced risks of >=30% decline in eGFR (hazard ratio [HR]: 0.77; 95% confidence
      interval [CI]: 0.66 to 0.89; p < 0.001), doubling of serum creatinine (HR: 0.62;
      95% CI: 0.40 to 0.95; p = 0.03), and AKI (HR: 0.68; 95% CI: 0.58 to 0.81; p <
      0.001) compared with warfarin. When comparing each NOAC with warfarin, dabigatran
      was associated with lower risks of >=30% decline in eGFR and AKI; rivaroxaban was
      associated with lower risks of >=30% decline in eGFR, doubling of serum
      creatinine, and AKI; however, apixaban did not have a statistically significant
      relationship with any of the renal outcomes. CONCLUSIONS: Renal function decline
      is common among patients with AF treated with oral anticoagulant agents. NOACs,
      particularly dabigatran and rivaroxaban, may be associated with lower risks of
      adverse renal outcomes than warfarin.

PMID- 29169469
TI  - Another Dimension of Safety in the Prescription of Anticoagulants for Nonvalvular
      Atrial Fibrillation.

PMID- 29169471
TI  - Fondaparinux for Treatment of Heparin-Induced Thrombocytopenia: Too Good to Be
      True?

PMID- 29169470
TI  - Use of Fondaparinux Off-Label or Approved Anticoagulants for Management of
      Heparin-Induced Thrombocytopenia.
AB  - BACKGROUND: Life-threatening heparin-induced thrombocytopenia (HIT) is treated
      with the alternative nonheparin anticoagulants argatroban, lepirudin, or
      danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label.
      OBJECTIVES: The authors sought to investigate the safety and efficacy of the
      different anticoagulants for treating HIT. METHODS: In a national, multicenter
      registry study, hospitalized patients who were diagnosed with HIT, an at least
      intermediate clinical HIT-risk (4Ts score >=4 points), and received treatment
      with >=1 dose of the aforementioned anticoagulants were included. Main outcome
      measures were the incidences of HIT-specific complications (thromboembolic
      venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin
      lesions) and bleedings. RESULTS: Of 195 patients, 46 (23.6%), 4 (2.1%), 61
      (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin,
      danaparoid, and fondaparinux, respectively. The composite endpoint of HIT
      specific complications (thromboembolic events, amputation, skin necrosis)
      occurred in 11.7% of patients treated with approved alternative anticoagulation
      and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality
      rates were 14.4% during approved alternative anticoagulation and 0.0% during
      fondaparinux treatment. Bleeding complications occurred in alternatively
      anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%,
      respectively. Post hoc analysis of clinical and laboratory features confirmed
      "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated
      with fondaparinux. CONCLUSIONS: Fondaparinux is effective and safe in suspected
      acute HIT; no HIT-specific complications occurred in the fondaparinux-treated
      patients, even among those with a high clinical HIT probability. Further data
      from randomized controlled trials are urgently needed because lepirudin was
      recalled from the market; danaparoid access has been limited and is not approved
      in the United States; and argatroban is contraindicated in patients with impaired
      liver function, and activated partial thromboplastin time confounding may
      interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin
      induced Thrombocytopenia Type II; NCT01304238).

PMID- 29169473
TI  - Xenon: A Noble Member of the Cardioprotection Club.

PMID- 29169472
TI  - Inhaled Xenon Attenuates Myocardial Damage in Comatose Survivors of Out-of
      Hospital Cardiac Arrest: The Xe-Hypotheca Trial.
AB  - BACKGROUND: The authors previously reported that inhaled xenon combined with
      hypothermia attenuates brain white matter injury in comatose survivors of out-of
      hospital cardiac arrest (OHCA). OBJECTIVES: A pre-defined secondary objective was
      to assess the effect of inhaled xenon on myocardial ischemic damage in the same
      study population. METHODS: A total of 110 comatose patients who had experienced
      OHCA from a cardiac cause were randomized to receive either inhaled xenon (40%
      end-tidal concentration) combined with hypothermia (33 degrees C) for 24 h (n =
      55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin
      T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post
      cardiac arrest. All available cases were analyzed for troponin-T release.
      RESULTS: Troponin-T measurements were available from 54 xenon patients and 54
      control patients. The baseline characteristics did not differ significantly
      between the groups. After adjustments for age, sex, study site, primary coronary
      percutaneous intervention (PCI), and norepinephrine dose, the mean +/- SD post
      arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 +/-
      1.54 in the xenon group and 1.56 +/- 1.38 in the control group (adjusted mean
      difference -0.66; 95% confidence interval: -1.16 to -0.16; p = 0.01). The effect
      of xenon on the change in the troponin-T values did not differ in patients with
      or without PCI or in those with a diagnosis of ST-segment elevation myocardial
      infarction (group by PCI or ST-segment elevation myocardial infarction
      interaction effect; p = 0.86 and p = 0.71, respectively). CONCLUSIONS: Among
      comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon
      combined with hypothermia suggested a less severe myocardial injury as
      demonstrated by the significantly reduced release of troponin-T.

PMID- 29169475
TI  - Outcomes in Pediatric Dilated Cardiomyopathy: Quo Vadis?

PMID- 29169474
TI  - Survival Without Cardiac Transplantation Among Children With Dilated
      Cardiomyopathy.
AB  - BACKGROUND: Studies of children with dilated cardiomyopathy (DCM) have suggested
      that improved survival has been primarily due to utilization of heart
      transplantation. OBJECTIVES: This study sought to determine transplant-free
      survival for these children over 20 years and identify the clinical
      characteristics at diagnosis that predicted death. METHODS: Children <18 years of
      age with some type of DCM enrolled in the Pediatric Cardiomyopathy Registry were
      divided by year of diagnosis into an early cohort (1990 to 1999) and a late
      cohort (2000 to 2009). Competing risks and multivariable modeling were used to
      estimate the cumulative incidence of death, transplant, and echocardiographic
      normalization by cohort and to identify the factors associated with death.
      RESULTS: Of 1,953 children, 1,199 were in the early cohort and 754 were in the
      late cohort. Most children in both cohorts had idiopathic DCM (64% vs. 63%,
      respectively). Median age (1.6 vs. 1.7 years), left ventricular end-diastolic z
      scores (+4.2 vs. +4.2), and left ventricular fractional shortening (16% vs. 17%)
      at diagnosis were similar between cohorts. Although the rates of
      echocardiographic normalization (30% and 27%) and heart transplantation (24% and
      24%) were similar, the death rate was higher in the early cohort than in the late
      cohort (18% vs. 9%; p = 0.04). Being in the early cohort (hazard ratio: 1.4; 95%
      confidence interval: 1.04 to 1.9; p = 0.03) independently predicted death.
      CONCLUSIONS: Children with DCM have improved survival in the more recent era.
      This appears to be associated with factors other than heart transplantation,
      which was equally prevalent in both eras. (Pediatric Cardiomyopathy Registry
      [PCMR]; NCT00005391).

PMID- 29169476
TI  - PCSK9 Inhibitors: Economics and Policy.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors substantially
      reduce low-density lipoprotein cholesterol, but it is presently unclear whether
      they also reduce mortality. The list prices of PCSK9 inhibitors in the United
      States (>$14,500 per year) are >100* higher than generic statins, and only a
      small fraction of their higher cost is likely to be recovered by prevention of
      cardiovascular events. The projected cost effectiveness of PCSK9 inhibitors does
      not meet generally accepted benchmarks for good value in the United States, but
      their value would be improved by substantial price reductions. For individual
      patients, the high out-of-pocket costs of PCSK9 inhibitors may impede access and
      reduce long-term adherence. The budgetary impact of PCSK9 inhibitors would be
      very large if all potentially eligible patients were treated, which poses
      dilemmas for policymakers, payers, and society.

PMID- 29169477
TI  - CPR Instruction in U.S. High Schools: What Is the State in the Nation?
AB  - Cardiopulmonary resuscitation (CPR) training in high schools is required by law
      in the majority of U.S. states. However, laws differ from state to state, and it
      is unknown how this legislation is being enacted. The authors sent a cross
      sectional, closed survey to educational superintendents in 32 states with CPR
      laws in June 2016. The authors subsequently performed direct examination and
      categorization of CPR legislation in 39 states (several states passed legislation
      as of September 2017). Survey results indicated differing practices with regard
      to CPR instruction in areas such as course content (63% perform automated
      external defibrillator training), instructor (47% used CPR-certified
      teachers/coaches, 30% used other CPR-certified instructors, 11% used noncertified
      teachers/coaches), and method (7% followed American Red Cross methods, 55%
      followed American Heart Association methods). CPR laws differ, although almost
      all (97%) require hands-on training. Although hands-on practice during CPR
      instruction in high school is required by law in the majority of U.S. states,
      there is currently no standardized method of implementation.

PMID- 29169478
TI  - 2017 Roadmap for Innovation-ACC Health Policy Statement on Healthcare
      Transformation in the Era of Digital Health, Big Data, and Precision Health: A
      Report of the American College of Cardiology Task Force on Health Policy
      Statements and Systems of Care.

PMID- 29169479
TI  - Leading the Digital Transformation of Healthcare: The ACC Innovation Strategy.

PMID- 29169480
TI  - Effect of a Formalized Research Curriculum on Fellows-in-Training and Early
      Career Research Productivity.

PMID- 29169481
TI  - Medicaid Insurance and Psychosocial Status in Patients Evaluated for Heart
      Transplantation.

PMID- 29169482
TI  - Heritable Thoracic Aortic Disease Genes in Sporadic Aortic Dissection.

PMID- 29169483
TI  - Reply: Improved Outcomes With Cardiology Care in Newly Diagnosed Atrial
      Fibrillation: Is Tachycardia-Induced Cardiomyopathy Underestimated?

PMID- 29169484
TI  - Improved Outcomes With Cardiology Care in Newly Diagnosed Atrial Fibrillation: Is
      Tachycardia-Induced Cardiomyopathy Underestimated?

PMID- 29169485
TI  - Authors Have Incorrectly Calculated Need for Renal Dose Adjustments for NOACs.

PMID- 29169486
TI  - Renal Risk Stratification Tool to Guide NOAC Dosing in Patients With Renal
      Dysfunction.

PMID- 29169487
TI  - NOAC Dosing in Atrial Fibrillation and Renal Dysfunction: What Measure Are You
      Using?

PMID- 29169489
TI  - Correction.

PMID- 29169488
TI  - Reply: NOAC Dosing in Patients With Atrial Fibrillation and Renal Dysfunction.

PMID- 29169490
TI  - Correction.

PMID- 29169491
TI  - Correction.

PMID- 29169492
TI  - Correction.

PMID- 29169493
TI  - Contemporary Arterial Access in the Cardiac Catheterization Laboratory.
AB  - Obtaining femoral and radial arterial access in the cardiac catheterization
      laboratory using state-of-the-art techniques is essential to optimize outcomes,
      patient satisfaction, and procedural efficiency. Although transradial access is
      increasingly used for coronary angiography and percutaneous coronary
      intervention, femoral access remains necessary for numerous procedures, many
      requiring large-bore access, including complex high-risk coronary interventions,
      structural procedures, and procedures involving mechanical circulatory support.
      For femoral access, contemporary access techniques should combine the use of
      fluoroscopy, ultrasound, micropuncture needle, femoral angiography, and vascular
      closure devices, when feasible. For radial access, ultrasound may reveal
      important anatomic features and expedite access. Despite randomized controlled
      trials supporting use of routine ultrasound guidance for femoral and/or radial
      arterial access, ultrasound remains underused in cardiac catheterization
      laboratories. This article reviews contemporary techniques to achieve optimal
      arterial access in the cardiac catheterization laboratory.

PMID- 29169495
TI  - 25 Years of Transradial Intervention: Looking Back and Anticipating What Is
      Ahead.

PMID- 29169494
TI  - Impact of Access Site Practice on Clinical Outcomes in Patients Undergoing
      Percutaneous Coronary Intervention Following Thrombolysis for ST-Segment
      Elevation Myocardial Infarction in the United Kingdom: An Insight From the
      British Cardiovascular Intervention Society Dataset.
AB  - OBJECTIVES: This study sought to examine the relationship between access site
      practice and clinical outcomes in patients requiring percutaneous coronary
      intervention (PCI) following thrombolysis for ST-segment elevation myocardial
      infarction (STEMI). BACKGROUND: Transradial access (TRA) is associated with
      better outcomes in patients requiring PCI for STEMI. A significant proportion of
      STEMI patients may receive thrombolysis before undergoing PCI in many countries
      across the world. There are limited data around access site practice and its
      associated outcomes in this cohort of patients. METHODS: The author used the
      British Cardiovascular Intervention Society dataset to investigate the outcomes
      of patients undergoing PCI following thrombolysis between 2007 and 2014. Patients
      were divided into TRA and transfemoral access groups depending on the access site
      used. Multiple logistic regression and propensity score matching were used to
      study the association of access site with in-hospital and long-term mortality,
      major bleeding, and access site-related complications. RESULTS: A total of 10,209
      patients received thrombolysis and PCI during the study time. TRA was used in 48%
      (n = 4,959) of patients; 3.3% (n = 336) patients died in hospital, 1.6% (n = 165)
      of patients experienced major bleeding, 4.2% (n = 437) experienced major adverse
      cardiac events (MACE), and 4.6% (n = 468) experienced 30-day mortality. After
      multivariate adjustment, TRA was associated with significantly reduced odds of in
      hospital mortality (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.42 to
      0.83; p = 0.002), major bleeding (OR: 0.45; 95% CI: 0.31 to 0.66; p < 0.001),
      MACE (OR: 0.72; 95% CI: 0.55 to 0.94; p = 0.01), and 30-day mortality (OR: 0.72;
      95% CI: 0.55 to 0.94; p = 0.01). CONCLUSIONS: TRA is associated with decreased
      odds of bleeding complications, mortality, and MACE in patients undergoing PCI
      following thrombolysis and should be preferred access site choice in this cohort
      of patients.

PMID- 29169497
TI  - Palpate-and-Stick, Still the Femoral Access Technique of Choice: Time for Change.

PMID- 29169496
TI  - Transfemoral Approach for Coronary Angiography and Intervention: A Collaboration
      of International Cardiovascular Societies.
AB  - OBJECTIVES: The aim of this study was to examine the current practice and use of
      transfemoral approach (TFA) for coronary angiography and intervention.
      BACKGROUND: Wide variability exists in TFA techniques for coronary procedures.
      METHODS: The authors developed a survey instrument that was distributed via e
      mail lists from professional societies to interventional cardiologists from 88
      countries between March and December 2016. RESULTS: Of 987 operators, 18% were
      femoralists, 38% radialists, 42% both, and 2% neither. Access using femoral pulse
      palpation alone was preferred by 60% of operators, fluoroscopy guidance by 11%,
      and a combination of palpation, fluoroscopy, or ultrasound by 27%. Only 11% used
      micropuncture in >90% of their cases. Performing femoral angiography immediately
      after access was preferred by 23% and at the end of the procedure by 47%, and not
      done at all by 31% of operators. Hemostasis by manual compression was preferred
      by 50%, collagen plug vascular closure device by 31%, and suture-based vascular
      closure device by 11% of operators. Judkins left and right catheters were
      preferred for diagnostic angiography of the left (99%) and right (94%) coronary
      arteries. Extra backup curves (XB or EBU) were most commonly preferred for
      percutaneous coronary intervention of the left anterior descending (80%) and left
      circumflex (80%), whereas the Judkins right catheter was preferred for
      percutaneous coronary intervention of the right coronary artery (86%).
      CONCLUSIONS: There is significant variability in preferences for femoral access
      technique. Even though recommended best practices advocate for fluoroscopic and
      ultrasound guidance, most operators use palpation alone. Femoral angiography is
      also not consistently used despite guideline recommendations. The lack of
      adoption of imaging guidance for vascular access deserves further investigation.

PMID- 29169499
TI  - Time to Redefine Critical Limb Ischemia.

PMID- 29169498
TI  - Heterogeneity of Ankle-Brachial Indices in Patients Undergoing Revascularization
      for Critical Limb Ischemia.
AB  - OBJECTIVES: This study sought to describe the distribution of pre-intervention
      treated-limb ankle-brachial indices (ABIs) among patients with critical limb
      ischemia (CLI) undergoing percutaneous vascular intervention (PVI) or surgical
      revascularization (SR). BACKGROUND: CLI is diagnosed by the presence of rest
      pain, tissue ulceration, or gangrene due to chronic arterial insufficiency. It is
      unclear what fraction of patients with suspected CLI have severe peripheral
      artery disease (PAD) on noninvasive functional testing. METHODS: The study
      included patients who underwent lower extremity revascularization for CLI in a
      multicenter registry in Michigan from January 2012 through June 2015. ABIs were
      classified as normal (ABI: 0.91 to 1.40), mild-moderate (ABI: 0.41 to 0.90), and
      severe (ABI: <=0.40). Pre- and post-intervention Peripheral Artery Questionnaire
      summary scores were assessed in a subset of patients. RESULTS: Among 10,756
      patients with signs or symptoms of CLI, 9,113 (84.7%) underwent PVI and 1,643
      (15.3%) underwent SR. ABIs were recorded in 4,972 (54.6%) PVI and 1,012 (61.6%)
      SR patients. Patients undergoing PVI had higher ABIs than those undergoing SR,
      with substantial variation in both groups (PVI: 0.72 +/- 0.29 vs. SR: 0.61 +/-
      0.29; p < 0.001). Nearly a quarter of patients with compressible arteries had
      normal ABIs (24.0%), whereas severe PAD was uncommon (16.5%). A significant
      improvement in Peripheral Artery Questionnaire scores was noted after
      intervention across all ABI categories. CONCLUSIONS: Among patients undergoing
      revascularization for CLI in contemporary practice, the authors found substantial
      heterogeneity in pre-intervention ABIs. The disconnect between ABI results and
      clinical diagnosis calls into question the utility of ABIs in this population and
      suggests the need for standardization of functional PAD testing.

PMID- 29169501
TI  - Stent Versus Scalpel in Peripheral Artery Disease: The Battle Continues to Rage
      On.

PMID- 29169500
TI  - 1-Year Results of a Multicenter Randomized Controlled Trial Comparing Heparin
      Bonded Endoluminal to Femoropopliteal Bypass.
AB  - OBJECTIVES: This study sought to compare heparin-bonded endografts with
      femoropopliteal bypass, including quality of life, using general health and
      disease-specific questionnaires as well as patency rates. BACKGROUND:
      Endovascular treatment continues to advance and is gaining acceptance as primary
      treatment for long occlusive or stenotic lesions in the superficial femoral
      artery. Heparin-bonded expanded polytetrafluoroethylene endografts have been
      related to outcomes comparable to bypass surgery, but this has not been tested in
      a randomized fashion. METHODS: A multicenter randomized-controlled trial was
      performed comparing femoropopliteal bypass with heparin-bonded expanded
      polytetrafluoroethylene endografts. Data were analyzed on an intention-to-treat
      and per-protocol manner. RESULTS: A total of 129 patients were randomized and 125
      patients were treated, 63 in the endoluminal and 62 in the surgical group (42
      venous, 20 prosthetic). Enrollment was terminated before reaching the predefined
      target number for patency. Baseline characteristics and anatomical data were
      similar. Patients were treated for critical limb ischemia in 38.1% and 32.2% in
      the endoluminal and surgical arms, respectively. Mean lesion length was 23 cm in
      both groups and lesions were largely TransAtlantic Inter-Society Consensus II D.
      Hospitalization time and 30-day morbidity were significantly lower in the
      endoluminal group, without differences in serious adverse events (n = 5 each;
      surgical: 4 venous and 1 polytetrafluoroethylene bypass). There were no
      significant differences in Rutherford category between groups at any time point.
      At 30 days the endoluminal group showed a greater improvement in quality-of-life
      scores. At 1 year, these differences had largely disappeared and no differences
      in primary (endoluminal: 64.8%; surgical: 63.6%), assisted primary (endoluminal:
      78.1%; surgical: 79.8%), secondary patency (endoluminal: 85.9%; surgical: 83.3%),
      and target vessel revascularization (endoluminal: 72.1%; surgical: 71.0%) were
      observed. Limb salvage rate was 100% in both groups. CONCLUSIONS: Heparin-bonded
      endoluminal bypass for long segment lesions shows promising results (less
      morbidity, faster recovery, and improvement in quality of life with
      indistinguishable patency rates at 1 year) compared with surgical bypass. Long
      term results have to be awaited.

PMID- 29169503
TI  - Reply: Repeated Intracoronary Imaging in Spontaneous Coronary Artery Dissection:
      Weighing Benefits and Risks.

PMID- 29169502
TI  - Re-Evaluating the Safety of Drug-Eluting Stents in Cancer Patients.
AB  - Evidence increasingly shows that cancer and coronary artery disease are
      interlinked through common risk factors, co-occurrence in an aging population,
      and through the deleterious effects of cancer treatment on cardiovascular health.
      Many of the clinical risk factors for cancer, such as diabetes, smoking, and
      chronic inflammatory state, are also risk factors for coronary artery disease and
      for stent restenosis and thrombosis. The current generations of drug-eluting
      stents have been proven to reduce the risk of restenosis and stent thrombosis as
      compared with bare-metal stents. However, because of the perceived need for
      shorter course of dual antiplatelet treatment, operators often prefer bare-metal
      stents in patients with cancer out of concern for increased bleeding risk and
      expectant need for cancer-directed surgery. The current evidence with newer
      generation stent technology demonstrates the feasibility of shorter duration of
      dual antiplatelet treatment, without increasing the risk of stent thrombosis and
      bleeding, while maintaining improved efficacy compared with bare-metal stents.
      Cardiovascular disease in patients with cancer is complex, and treatment needs to
      be individualized. Refraining from the use of drug-eluting stents altogether in
      this rapidly expanding cohort may lead to higher major adverse cardiovascular
      events, which can thwart the effectiveness of advances in both cancer and
      cardiovascular therapeutics. Considering the developing evidence thus far,
      perhaps it is time to rethink the choice of stent in patients with cancer who
      undergo percutaneous coronary intervention.

PMID- 29169504
TI  - Repeated Intracoronary Imaging in Spontaneous Coronary Artery Dissection:
      Weighing Benefits and Risks.

PMID- 29169505
TI  - Research and Therapeutic Nihilisms in Chronic Kidney Disease.

PMID- 29169506
TI  - Reply: Research and Therapeutic Nihilisms in Chronic Kidney Disease.

PMID- 29169507
TI  - Prognostic Implications of Pre-Procedural High-Sensitivity Cardiac Troponin T in
      Patients Undergoing Transcatheter Aortic Valve Replacement.

PMID- 29169508
TI  - Research Correspondence: One Good Point, One Great Figure (or Table).

PMID- 29169509
TI  - T-Time again - The diversity of actions of thyroid hormones (TH), their aminergic
      (TAM) and acetic acid (TAc) metabolites.

PMID- 29169510
TI  - Relationships matter in oral cancer: will single-stain immunohistochemistry
      become irrelevant in the age of multispectral imaging?

PMID- 29169511
TI  - Longitudinal and cross-sectional assessment of quality of life in surgically
      treated advanced (T4) cancer of the buccal mucosa.
AB  - OBJECTIVE: Quality of life (QOL) has become an important aspect of today's health
      care management. This study performed longitudinal assessment of QOL in patients
      with advanced cancers of the buccal mucosa (T4). We compared the QOL between
      patients who received adjuvant chemoradiation therapy (CTRT) and that of patients
      who received radiation therapy alone and assessed whether baseline QOL can
      predict disease recurrence. STUDY DESIGN: This was a prospective study of 225
      patients with T4 buccal mucosal cancer. Health-related QOL was assessed at
      baseline and at 3, 6, 9, and 12 months after completion of treatment by means of
      the European Organization for Research and Treatment of Cancer Core QOL
      Questionnaire and the HN35 questionnaire. RESULTS: There was persistent
      improvement in global QOL and pain. Emotional functioning improved at 12 months.
      Most of the head and neck-specific symptoms deteriorated at 3 months, with
      subsequent improvement at 12 months except in swallowing, senses, speech, social
      eating, social contact, and sexuality. Patients who received adjuvant CTRT had
      poorer QOL. Poorer baseline global QOL (P = .049), dyspnea (P = .04), appetite
      loss (P = .015), and weight loss (P = .08) may predict recurrence. CONCLUSIONS:
      Although there is an improvement in global QOL and pain, most of the head and
      neck-specific symptoms worsened in the immediate postoperative period. Adjuvant
      CTRT has a persistent effect on specific domains compared with adjuvant radiation
      therapy alone. Poor baseline QOL scores are associated with a higher risk of
      recurrence.

PMID- 29169512
TI  - Radiation-related caries assessment through the International Caries Detection
      and Assessment System and the Post-Radiation Dental Index.
AB  - OBJECTIVE: Although radiation-related caries (RRC) are a well-known toxicity of
      head and neck radiotherapy, a clinical classification system for RRC has not yet
      been clinically validated. Therefore, the aim of this study was to assess whether
      the International Caries Detection and Assessment System (ICDAS) and the Post
      Radiation Dental Index (PRDI) were viable methods for the assessment of RRC.
      STUDY DESIGN: Clinicopathologic data and intraoral digital photographs of 60
      patients (833 teeth) affected by RRC were assessed and classified according to
      the ICDAS and PRDI criteria. RESULTS: A total of 814 (97.7%) teeth presented RRC
      lesions ranging from early stage to complete tooth destruction. Mean scores for
      the whole sample were 5 for ICDAS and 3 for PRDI, indicating that RRC were
      diagnosed predominately in late stages. ICDAS and PRDI criteria underestimate the
      clinical expressivity of RRC by not including the whole qualitative clinical
      spectrum of RRC, such as enamel cracks, delamination, dental crown amputation,
      surface color alterations, and atypical lesions topography (incisal/cuspal
      caries). CONCLUSIONS: ICDAS and PRDI may not be considered viable for the
      assessment of RRC. The development of a specific clinical classification system
      is urgently needed to help clinicians recognize the peculiar patterns of RRC,
      particularly in incipient cases.

PMID- 29169514
TI  - Serum Uric Acid Levels and Kidney Transplant Outcomes: Cause, Consequence, or
      Confounded?

PMID- 29169513
TI  - The reliability of different methods of manual volumetric segmentation of
      pharyngeal and sinonasal subregions.
AB  - OBJECTIVES: The purpose of the study was to test the intra and interobserver
      reliability of manual volumetric segmentation of pharyngeal and sinonasal airway
      subregions. STUDY DESIGN: Cone beam computed tomography data of 15 patients were
      collected from an orthodontic clinical database. Two experienced orthodontists
      independently performed manual segmentation of the airway subregions. Four
      performance measures were considered to test intra and interobserver reliability
      of manual segmentation: (1) volume correlation, (2) mean slice correlation, (3)
      percentage of volume difference, and (4) percentage of nonoverlapping voxels.
      RESULTS: Intra and interobserver reliability was observed to be greater than 0.96
      for the entire pharyngeal and sinonasal airway sinus subregions by both observers
      using the volume correlation method. Mean slice correlation was found to be
      greater than 0.84, showing the existence of nonoverlapping voxels. Therefore, the
      percentage of nonoverlapping voxels was used as a reliability measure and was
      found to be less than 20% for both intra and interobserver markings. CONCLUSIONS:
      The mean slice correlation and percentage of nonoverlapping voxels were the most
      reliable performance measures of segmentation correctness. Volume correlation and
      the percentage of volume difference were observed to be the most reliable
      performance measures for volume correctness.

PMID- 29169515
TI  - Kidney Transplantation in Patients With Atypical Hemolytic Uremic Syndrome: A
      Therapeutic Dilemma (or Not)?

PMID- 29169516
TI  - 73 Cents: A Mural.

PMID- 29169517
TI  - A 61-Year-Old Man With Membranoproliferative Glomerulonephritis.

PMID- 29169518
TI  - AJKD Atlas of Renal Pathology: Cystinosis.

PMID- 29169519
TI  - Critical Access to Care: Bringing Contraception to Adolescents in Nontraditional
      Settings.

PMID- 29169520
TI  - Heterosexual Practices Among Young People in Britain: Evidence From Three
      National Surveys of Sexual Attitudes and Lifestyles.
AB  - PURPOSE: To describe time trends and current patterns in sexual practices with
      opposite-sex partners among men and women aged 16-24 years in Britain. METHODS:
      Complex survey analyses of cross-sectional probability survey data from three
      British National Surveys of Sexual Attitudes and Lifestyles (Natsal), conducted
      approximately decennially 1990-2012, involving interviews with 45,199 people in
      total. RESULTS: Birth cohort analysis showed a decline in the median age at first
      sexual experience and first intercourse since the midtwentieth century and a
      narrowing of the interval between these events. Comparison of data from Natsals
      1, 2, and 3 showed increases in the prevalence of ever experience of oral and
      anal sex among 16- to 24-year-olds, which were more marked among older
      respondents in this age group between Natsals 1 and 2, and among younger
      respondents between Natsals 2 and 3. Among the sexually active, vaginal and oral
      sex remained the most common combination of practices reported in the past year.
      The proportion reporting a past-year repertoire of vaginal, oral, and anal sex
      rose from approximately one in 10 in 1990-1991 to approximately one in four men
      and one in five women in 2010-2012. In the latest survey, heterosexual experience
      of practices was positively associated with bisexual attraction among women.
      CONCLUSIONS: Recent decades have seen an earlier age at initiation of partnered
      sexual experiences and increased diversity in heterosexual practices among young
      people. Keeping pace with trends in sexual practices is necessary to safeguard
      young people's health and to support them in increasing their sexual well-being.

PMID- 29169521
TI  - Addressing Underrepresented Populations in Lung Cancer Research: The
      Hispanic/Latino Lung Cancer Registry Identifies Distinct Mutation Profiles for
      NSCLC.

PMID- 29169522
TI  - Erratum to: Pyo KH, Lim SM, Kim HR, Sung YH, Yun MR, Kim S-M, et al.
      Establishment of a Conditional Transgenic Mouse Model Recapitulating EML4-ALK
      Postive Human Non-Small Cell Lung Cancer. J Thorac Oncol. 2017;12(3):491-500.

PMID- 29169524
TI  - A Case of Invasive Mucinous Pulmonary Adenocarcinoma with a CD74-NRG1 Fusion
      Protein Targeted with Afatinib.

PMID- 29169523
TI  - Combination Treatment Using an EGFR Tyrosine Kinase Inhibitor plus Platinum-Based
      Chemotherapy for a Patient with Transformed Small Cell Carcinoma and EGFR-Mutated
      Lung Adenocarcinoma.

PMID- 29169525
TI  - Case Report of Non-Small Cell Lung Cancer with STRN-ALK Translocation: A
      Nonresponder to Alectinib.

PMID- 29169526
TI  - Complete Response Achieved 1 Year after a Single Administration of Nivolumab in a
      Patient with Lung Adenocarcinoma with Negative Expression of PD-L1.

PMID- 29169527
TI  - Comments on Potential Impact of Including Time to First Cigarette in Risk Models
      for Selecting Ever-Smokers For Lung Cancer Screening.

PMID- 29169528
TI  - Response to Safiri et al. "Comments on Potential Impact of Including Time to
      First Cigarette in Risk Models for Selecting Ever-Smokers for Lung Cancer
      Screening".

PMID- 29169529
TI  - Impressive Response to Tyrosine Kinase Inhibitors in a Patient with Respiratory
      Failure for EGFR-Mutated Metastatic Lung Cancer.

PMID- 29169530
TI  - Labour market entries and exits of women from different origin countries in the
      UK.
AB  - Labour force participation rates of women differ strongly by ethnic origin. Even
      though existing research using cross-sectional studies has demonstrated that part
      of these differences can be attributed to compositional differences in human
      capital, household conditions and gender attitudes, residual 'ethnic effects'
      typically remain. To further our understanding of women's labour market behaviour
      across ethnic groups, we use a large-scale longitudinal study and apply a dynamic
      perspective to examine how far relevant life-course events in addition to
      individual characteristics, gender attitudes and religiosity contribute to the
      explanation of ethnic differences in women's labour force entries and exits in
      the UK. Our findings show that, adjusting for all these factors, Indian and
      Caribbean women do not differ from White majority women in their labour force
      entry and exit probabilities but that Pakistani and Bangladeshi women are less
      likely to enter and more likely to exit the labour market, whereas Black African
      women have higher entry rates. We also find that relations between life-course
      events and labour market transitions differ by ethnic group. Most notably,
      Pakistani and Bangladeshi women's labour market transitions are less sensitive to
      child-bearing and Caribbean women's transitions less sensitive to partnership
      changes than other women's.

PMID- 29169531
TI  - For everything a season? A month-by-month analysis of social network resources in
      later life.
AB  - It is widely acknowledged that informal social ties provide older persons with
      many resources that serve to protect and improve their levels of health and well
      being. Most studies on this topic, however, ignore the month or season of the
      year during which data was accumulated. This study proposes two hypotheses to
      explain seniors' social network resources over the calendar year: the
      "fluctuation hypothesis", which proposes that seasonal variation, in the form of
      weather fluctuations, institutional calendars, and holidays, might influence the
      social lives and resources of older persons, and the "network stability"
      perspective, which, informed by tenets of convoy theory and socioemotional
      selectivity theory, emphasizes the increasing importance of close network ties as
      individuals age and the stability of these ties. Using two waves (2005-2006 and
      2010-2011) of the National Social Life, Health, and Aging Project (NSHAP), a
      nationally representative sample of community-dwelling older adults aged 57-85 in
      the United States, we examine a diverse set of nine social connectedness
      outcomes. Results, overall, support the network stability perspective, as the
      only social connectedness outcome found to significantly vary by month of year
      was average closeness with network members. We conclude by suggesting some
      methodological considerations for survey research and by noting how these
      findings complement the growing literature on inter-year fluctuation in social
      networks and social support. Changes in older adults' networks, while frequently
      observable over the course of years, do not seem to be seasonally patterned.

PMID- 29169532
TI  - Barrios, ghettos, and residential racial composition: Examining the racial makeup
      of neighborhood profiles and their relationship to self-rated health.
AB  - Racial/ethnic disparities in self-rated health persist and according to the
      social determinants of health framework, may be partially explained by
      residential context. The relationship between neighborhood factors and self-rated
      health has been examined in isolation but a more holistic approach is needed to
      understand how these factors may cluster together and how these neighborhood
      typologies relate to health. To address this gap, we conducted a latent profile
      analysis using data from the Chicago Community Adult Health Study (CCAHS; N =
      2969 respondents in 342 neighborhood clusters) to identify neighborhood profiles,
      examined differences in neighborhood characteristics among the identified
      typologies and tested their relationship to self-rated health. Results indicated
      four distinct classes of neighborhoods that vary significantly on most
      neighborhood-level social determinants of health and can be defined by
      racial/ethnic composition and class. Residents in Hispanic, majority black
      disadvantaged, and majority black non-poor neighborhoods all had significantly
      poorer self-rated health when compared to majority white neighborhoods. The
      difference between black non-poor and white neighborhoods in self-rated health
      was not significant when controlling for individual race/ethnicity. The results
      indicate that neighborhood factors do cluster by race and class of the
      neighborhood and that this clustering is related to poorer self-rated health.

PMID- 29169533
TI  - Leaving late: Understanding the extent and predictors of college late departure.
AB  - Research on college dropout has largely addressed early exit from school, even
      though a large share of students who do not earn degrees leave after their second
      year. In this paper, we offer new evidence on the scope of college late
      departure. Using administrative data from Florida and Ohio, we conduct an event
      history analysis of the dropout process as a function of credit attainment. Our
      results indicate that late departure is widespread, particularly at two- and open
      admission four-year institutions. We estimate that 14 percent of all entrants to
      college and one-third of all dropouts completed at least three-quarters of the
      credits that are typically required to graduate before leaving without a degree.
      Our results also indicate that the probability of departure spikes as students
      near the finish line. Amidst considerable policy attention towards improving
      student outcomes in college, our findings point to promising new avenues for
      intervention to increase postsecondary attainment.

PMID- 29169534
TI  - Race, ageism and the slide from privileged occupations.
AB  - The sociological literature on workplace inequality has been relatively clear
      regarding racial disparities and ongoing vulnerabilities to contemporary
      structural and employer biases. We still know little, however, about the
      consequences of age and ageism for minority workers and susceptibilities to
      downward mobility. Coupling insights regarding race with recent work on
      employment-based age discrimination, we interrogate in this article African
      Americans and Whites, aged 55 and older, and the extent to which they experience
      job loss across time. Our analyses, beyond controlling for key background
      attributes, distinguish and disaggregate patterns for higher and lower level
      status managers and professionals and for men and women. Results, derived from
      data from the Panel Study of Income Dynamics, reveal unique and significant
      inequalities. Relative to their White and gender specific counterparts, older
      African American men and women experience notably higher rates of downward
      mobility-downward mobility that is not explained by conventional explanations
      (i.e., human capital credentials, job/labor market characteristics, etc.). Such
      inequalities are especially pronounced among men and for those initially
      occupying higher status white-collar managerial and professional jobs compared to
      technical/skilled professional and blue-collar "first line" supervisors. We tie
      our results to contemporary concerns regarding ageism in the workplace as well as
      minority vulnerability. We also suggest an ageism-centered corrective to existing
      race and labor market scholarship.

PMID- 29169535
TI  - One flag, two rallies: Mechanisms of public opinion in Israel during the 2014
      Gaza war.
AB  - In Israel, public reaction to the 2014 Gaza war included massive support for the
      military operation and a sharp increase in the popularity of Prime Minister
      Netanyahu. To understand what caused these "rally-round-the-flag" (RRTF) effects,
      panel data were collected from a representative sample of the Jewish majority in
      Israel during and after the war. The article integrate empirical and theoretical
      arguments from public opinion studies, and from social and political psychology,
      to contextualize and guide the analysis. The results reveal that perceived threat
      to collective security produced two simultaneous rally outcomes through distinct
      processes: First, increased identification with the ethno-national Jewish group
      led to a rally behind Israel's prime minister. Second, anger toward Hamas and
      sentiment of national superiority, which was activated by increased ethno
      national identification, produced a rally behind the military operation. In
      addition to explaining its specific empirical case, this study makes three
      broader contributions. First, it extends the investigation of the RRTF phenomenon
      in wartime beyond the popularity of the head of the state (the focus of most
      previous studies) by also examining levels of support for the use of military
      power. Second, it reveals some of the mechanisms through which distinct elements
      of popular nationalism mediate the relationship between war events and
      heterogeneous rally effects. Third, this study shows that the mechanisms that
      have been detected in studies of individual attitudes and behavior in small
      groups under conditions of perceived threat or competition can help explain the
      behavior of these individuals as members of larger, imagined national communities
      during war.

PMID- 29169538
TI  - Invited commentary.

PMID- 29169536
TI  - Countervailing contact: Community ethnic diversity, anti-immigrant attitudes and
      mediating pathways of positive and negative inter-ethnic contact in European
      societies.
AB  - Inter-ethnic contact has long been held as a key means of ameliorating possible
      inter-group tensions and facilitating the integration of increasing immigrant
      populations into society. However, our understanding of the role of contact in
      this relationship may be limited due to the omission of contact-valence; that is,
      whether contact is experienced positively or negatively. This paper integrates
      the concept of contact-valence into the question of how increasing community
      diversity affects attitudes towards immigrants via inter-group contact, across
      Europe. We posit the existence of dual, mediating pathways of both positive and
      negative inter-group contact. Applying generalized structural equation models to
      data from the 2014 European Social Survey, we find that living in more diverse
      communities increases the frequency of positive inter-group contact but also
      negative inter-group contact. While the former is positively associated with
      inter-group attitudes the latter is negatively associated. Testing demonstrates
      that diversity exerts countervailing positive and negative indirect-effects on
      attitudes towards immigrants via processes of inter-group contact. Furthermore,
      while the net-effect of diversity on attitudes via contact is positive, attitudes
      amongst those experiencing more frequent negative contact become progressively
      worse. Increasing diversity therefore leads to a polarisation in attitudes
      towards immigration as a result of, and not due to a lack of, inter-group
      contact.

PMID- 29169539
TI  - Invited commentary.

PMID- 29169541
TI  - Invited commentary.

PMID- 29169540
TI  - Retroperitoneoscopic lumbar sympathectomy for plantar hyperhidrosis.
AB  - OBJECTIVE: The objective of this study was to assess the reduction in quality of
      life (QoL) caused by the persistence of primary plantar hyperhidrosis (PPH)
      symptoms and the level of satisfaction in PPH patients after retroperitoneoscopic
      lumbar sympathectomy (RLS). The efficacy, safety, and procedure of bilateral RLS
      in both sexes are also described in this study. METHODS: This is a longitudinal
      study of consecutive patients who sought specific treatment from a private
      practitioner for severe PPH as classified on the Hyperhidrosis Disease Severity
      Scale (HDSS) from October 2005 to October 2014. The patients were asked to report
      the symptoms of PPH experienced in the immediate preoperative period and to
      complete a standardized QoL questionnaire developed by de Campos at least 12
      months after RLS. Disease outcomes, recurrence of symptoms, and any adverse
      effects of surgery were evaluated after 30 days and at least 12 months after RLS.
      RESULTS: Lumbar sympathectomy was performed 116 times in 58 patients; 30 days
      after surgery, PPH was resolved in all patients. Three patients (5.2%) reported
      transient thigh neuralgia, and 19 (32.7%) reported transient paresthesia in the
      lower limbs. There were no reports of retrograde ejaculation. At a minimum of 12
      months after RLS, 49 of the 58 patients had fully and correctly answered the
      follow-up questionnaire and noted a mild (HDSS 2) to moderate (HDSS 3) increase
      in pre-existing compensatory sweating. One patient had a PPH relapse within 6
      months. Improvement in QoL due to the resolution of PPH was reported in 98% of
      the 49 patients. None of the operations necessitated a change in the laparotomy
      approach, and none of the patients died. CONCLUSIONS: RLS is safe and effective
      for the treatment of severe PPH in both sexes. There were no reports of
      retrograde ejaculation after resection of L3 and L4 ganglia. There was a mild to
      moderate increase in compensatory sweating in about half of the patients, but
      without any regret or dissatisfaction for having undergone the surgery because of
      a significant improvement in QoL.

PMID- 29169542
TI  - Invited commentary.

PMID- 29169543
TI  - Repeat presentation for middle aortic syndrome 18 years after original repair.

PMID- 29169544
TI  - Systematic review and meta-analysis of duplex ultrasound surveillance for
      infrainguinal vein bypass grafts.
AB  - OBJECTIVE: Duplex ultrasound (DUS) surveillance of infrainguinal vein bypass
      grafts is widely practiced, but the evidence of its effectiveness compared with
      other methods of surveillance remains unclear. METHODS: Following an a priori
      protocol developed by the guidelines committee from the Society for Vascular
      Surgery, this systematic review and meta-analysis included randomized and
      nonrandomized comparative studies that enrolled patients who underwent
      infrainguinal arterial reconstruction and received DUS surveillance for follow-up
      compared with any other method of surveillance. The search included MEDLINE,
      Embase, Cochrane Central Register of Controlled Trials and Cochrane Database of
      Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, and
      Scopus through November 2016. Outcomes of interest included all-cause mortality,
      limb viability, and graft patency reports. Meta-analysis was performed using the
      random-effects model. RESULTS: We included 15 studies. Compared with ankle
      brachial index and clinical examination, DUS surveillance was not associated with
      a significant change in primary, secondary, or assisted primary patency or
      mortality. DUS surveillance was associated with a nonstatistically significant
      reduction in amputation rate (odds ratio, 0.70 [95% confidence interval, 0.23
      2.13]). The quality of evidence was low because of imprecision (small number of
      events and wide confidence intervals) and high risk of bias in the primary
      literature. CONCLUSIONS: A recommendation for routine DUS surveillance of
      infrainguinal vein grafts remains dependent on low-quality evidence. Considering
      that DUS offers the opportunity of early intervention and because of its
      noninvasive nature and low cost, vascular surgeons may incorporate DUS as they
      individualize the follow-up of lower extremity vein grafts.

PMID- 29169545
TI  - An evaluation of the availability, accessibility, and quality of online content
      of vascular surgery training program websites for residency and fellowship
      applicants.
AB  - BACKGROUND: Vascular surgery residency and fellowship applicants commonly seek
      information about programs from the Internet. Lack of an effective web presence
      curtails the ability of programs to attract applicants, and in turn applicants
      may be unable to ascertain which programs are the best fit for their career
      aspirations. This study was designed to evaluate the presence, accessibility,
      comprehensiveness, and quality of vascular surgery training websites (VSTW).
      METHODS: A list of accredited vascular surgery training programs (integrated
      residencies and fellowships) was obtained from four databases for vascular
      surgery education: the Accreditation Council for Graduate Medical Education,
      Electronic Residency Application Service, Fellowship and Residency Electronic
      Interactive Database, and Society for Vascular Surgery. Programs participating in
      the 2016 National Resident Matching Program were eligible for study inclusion.
      Accessibility of VSTW was determined by surveying the Accreditation Council for
      Graduate Medical Education, Electronic Residency Application Service, and
      Fellowship and Residency Electronic Interactive Database for the total number of
      programs listed and for the presence or absence of website links. VSTW were
      analyzed for the availability of recruitment and education content items. The
      quality of VSTW was determined as a composite of four dimensions: content,
      design, organization, and user friendliness. Percent agreements and kappa
      statistics were calculated for inter-rater reliability. RESULTS: Eighty-nine of
      the 94 fellowship (95%) and 45 of the 48 integrated residencies (94%) programs
      participating in the 2016 Match had a VSTW. For program recruitment, evaluators
      found an average of 12 of 32 content items (35.0%) for fellowship programs and an
      average of 12 of 32 (37%) for integrated residencies. Only 47.1% of fellowship
      programs (53% integrated residencies) specified the number of positions available
      for the 2016 Match, 20% (13% integrated residencies) indicated alumni career
      placement, 34% (38% integrated residencies) supplied interview dates, and merely
      17% (18% integrated residencies) detailed the selection process. For program
      education, fellowship websites provided an average of 5.1 of 15 content items
      (34.0%), and integrated residency websites provided 5 of 14 items (34%). Of the
      fellowship programs, 66% (84.4% integrated residencies) provided a rotation
      schedule, 65% (56% integrated residencies) detailed operative experiences, 38%
      (38% integrated residencies) posted conference schedules, and just 16% (28.9%
      integrated residencies) included simulation training. CONCLUSIONS: The web
      presence of vascular surgery training programs lacks sufficient accessibility,
      content, organization, design, and user friendliness to allow applicants to
      access information that informs them sufficiently. There are opportunities to
      more effectively use VSTW for the benefit of training programs and prospective
      applicants.

PMID- 29169546
TI  - Telehealth electronic monitoring to reduce postdischarge complications and
      surgical site infections after arterial revascularization with groin incision.
AB  - It is intuitive that postdischarge surgical complications are associated with
      increased patient dissatisfaction, and are directly associated with an increase
      in medical expenditures. It is also easy to make the connection that many post
      hospital discharge surgical complications, including surgical site infections
      (SSIs), could be influenced or exacerbated by patient comorbidities. The authors
      of a recent study reported that female gender, obesity, diabetes, smoking,
      hypertension, coronary artery disease, critical limb ischemia, chronic
      obstructive pulmonary disease, dyspnea, and neurologic disease were significant
      predictors of SSIs after vascular reconstruction was performed. The main concern
      for optimal patient care, especially in geographically isolated areas of West
      Virginia, is to have early, expeditious, and prompt diagnosis of complications
      and SSI. This adjunct to existing approaches could lead to improved outcomes and
      patient satisfaction, minimizing third-party interventions and decreasing the
      total cost of care. It seems reasonable to believe that monitoring using
      telehealth technology and managing the general health care of patients after a
      hospital vascular intervention will improve overall health and reduce 30-day
      readmissions and SSIs.

PMID- 29169547
TI  - Tips for participating in the Quality Payment Program in 2018 and beyond.

PMID- 29169548
TI  - Reply.

PMID- 29169549
TI  - Regarding "Predictive value of neutrophil-to-lymphocyte ratio in diabetic wound
      healing".

PMID- 29169550
TI  - Regarding "Sex differences in mortality and morbidity following repair of intact
      abdominal aortic aneurysms".

PMID- 29169551
TI  - Reply.

PMID- 29169552
TI  - Regarding "Increased risk of mortality after lower extremity bypass in
      individuals with acute kidney injury in the Vascular Quality Initiative".

PMID- 29169553
TI  - Regarding "Upregulated interleukins (IL-6, IL-10, and IL-13) in immunoglobulin G4
      related aortic aneurysm patients".

PMID- 29169554
TI  - Reply.

PMID- 29169555
TI  - Is Hutchinson's Sign Pathogonomic of Subungual Melanoma?

PMID- 29169556
TI  - Human Papilloma Virus and the Risk of Squamous Cell Carcinoma Arising in
      Hidradenitis Suppurativa.

PMID- 29169557
TI  - Macro lens for mirrorless cameras in digital photography in dermatology.

PMID- 29169558
TI  - After Decades Without any Developments, New Drugs May Revolutionize the Treatment
      of Atopic Dermatitis.

PMID- 29169559
TI  - Fleeting Macules on the Trunk and Limbs.

PMID- 29169560
TI  - Closure of Large Lower Lip Defects: Combining a Karapandzic Flap and a
      Contralateral Sliding Flap.

PMID- 29169561
TI  - Atypical Vesicular-Bullous Hand-Foot-Mouth Disease in 2 Adults.

PMID- 29169562
TI  - Response to Secukinumab after Treatment Failure with Ustekinumab in 6 Patients
      with Plaque Psoriasis.

PMID- 29169563
TI  - Historical reflections on neurosyphilis based on the 1826 treatise on general
      paralysis in demented patients by Louis Florentin Calmeil (1798-1895).
AB  - General paralysis is a neurological symptom of tertiary syphilis that was first
      identified in asylums as paralytic madness. The enlightened discussion of 60
      clinicopathological cases provided by Louis Florentin Calmeil in his 1826
      treatise greatly improved our knowledge of general paralysis. However, Calmeil
      was unable to relate this symptom to syphilis, although the latter was quite
      widespread at that time. Following a detailed reanalysis of Calmeil's
      observations with special attention to his clinical and demographic data, we
      conclude that this eminent clinician was unable to define the cause of general
      paralysis because his early 19th century mind was still under the influence of
      traditional knowledge and moral prejudices. For Calmeil, general paralysis
      belonged entirely to the realm of psychiatry.

PMID- 29169564
TI  - The Ninth 2016 International London Cough Symposium.

PMID- 29169565
TI  - Septic systems contribute to nutrient pollution and harmful algal blooms in the
      St. Lucie Estuary, Southeast Florida, USA.
AB  - Nutrient enrichment is a significant global-scale driver of change in coastal
      waters, contributing to an array of problems in coastal ecosystems. The St. Lucie
      Estuary (SLE) in southeast Florida has received national attention as a result of
      its poor water quality (elevated nutrient concentrations and fecal bacteria
      counts), recurring toxic Microcystis aeruginosa blooms, and its proximity to the
      northern boundary of tropical coral species in the United States. The SLE has an
      artificially large watershed comprised of a network of drainage canals, one of
      which (C-44) is used to lower the water level in Lake Okeechobee. Public
      attention has primarily been directed at nutrient inputs originating from the
      lake, but recent concern over the importance of local watershed impacts prompted
      a one-year watershed study designed to investigate the interactions between on
      site sewage treatment and disposal systems (OSTDS or septic systems),
      groundwaters, and surface waters in the SLE and nearshore reefs. Results provided
      multiple lines of evidence of OSTDS contamination of the SLE and its watershed:
      1) dissolved nutrients in groundwaters and surface waters were most concentrated
      adjacent to two older (pre-1978) residential communities and the primary canals,
      and 2) sucralose was present in groundwater at residential sites (up to
      32.0MUg/L) and adjacent surface waters (up to 5.5MUg/L), and 3) delta15N values
      in surface water (+7.5 o/oo), macroalgae (+4.4 o/oo) and phytoplankton (+5.0
      o/oo) were within the published range (>+3 o/oo) for sewage N and similar to
      values in OSTDS-contaminated groundwaters. Measured delta15N values in M.
      aeruginosa became increasingly enriched during transport from the C-44 canal
      (~5.8 o/oo) into the mid-estuary (~8.0 o/oo), indicating uptake and growth on
      sewage N sources within the urbanized estuary. Consequently, there is a need to
      reduce N and P loading, as well as fecal loading, from the SLE watershed via
      septic-to-sewer conversion projects and to minimize the frequency and intensity
      of the releases from Lake Okeechobee to the SLE via additional water storage
      north of the lake. These enhancements would improve water quality in both the SLE
      and Lake Okeechobee, reduce the occurrence of toxic harmful algal blooms in the
      linked systems, and improve overall ecosystem health in the SLE and downstream
      reefs.

PMID- 29169566
TI  - A multilevel trait-based approach to the ecological performance of Microcystis
      aeruginosa complex from headwaters to the ocean.
AB  - The Microcystis aeruginosa complex (MAC) clusters cosmopolitan and conspicuous
      harmful bloom-forming cyanobacteria able to produce cyanotoxins. It is
      hypothesized that low temperatures and brackish salinities are the main barriers
      to MAC proliferation. Here, patterns at multiple levels of organization
      irrespective of taxonomic identity (i.e. a trait-based approach) were analyzed.
      MAC responses from the intracellular (e.g. respiratory activity) to the ecosystem
      level (e.g. blooms) were evaluated in wide environmental gradients. Experimental
      results on buoyancy and respiratory activity in response to increased salinity (0
      35) and a literature review of maximum growth rates under different temperatures
      and salinities were combined with field sampling from headwaters (800km upstream)
      to the marine end of the Rio de la Plata estuary (Uruguay-South America).
      Salinity and temperature were the major variables affecting MAC responses.
      Experimentally, freshwater MAC cells remained active for 24h in brackish waters
      (salinity=15) while colonies increased their flotation velocity. At the
      population level, maximum growth rate decreased with salinity and presented a
      unimodal exponential response with temperature, showing an optimum at 27.5
      degrees C and a rapid decrease thereafter. At the community and ecosystem levels,
      MAC occurred from fresh to marine waters (salinity 30) with a sustained relative
      increase of large mucilaginous colonies biovolume with respect to individual
      cells. Similarly, total biomass and, specific and morphological richness
      decreased with salinity while blooms were only detected in freshwater both at
      high (33 degrees C) and low (11 degrees C) temperatures. In brackish waters,
      large mucilaginous colonies presented advantages under osmotic restrictive
      conditions. These traits values have also been associated with higher toxicity
      potential. This suggest salinity or low temperatures would not represent
      effective barriers for the survival and transport of potentially toxic MAC under
      likely near future scenarios of increasing human impacts (i.e. eutrophication,
      dam construction and climate change).

PMID- 29169567
TI  - Sandwich hybridization probes for the detection of Pseudo-nitzschia
      (Bacillariophyceae) species: An update to existing probes and a description of
      new probes.
AB  - New sandwich hybridization assay (SHA) probes for detecting Pseudo-nitzschia
      species (P. arenysensis, P. fraudulenta, P. hasleana, P. pungens) are presented,
      along with updated cross-reactivity information on historical probes (SHA and
      FISH; fluorescence in situ hybridization) targeting P. australis and P.
      multiseries. Pseudo-nitzschia species are a cosmopolitan group of diatoms that
      produce varying levels of domoic acid (DA), a neurotoxin that can accumulate in
      finfish and shellfish and transfer throughout the food web. Consumption of
      infected food sources can lead to illness in humans (amnesic shellfish poisoning;
      ASP) and marine wildlife (domoic acid poisoning; DAP). The threat of human
      illness, along with economic loss from fishery closures has resulted in the
      implementation of monitoring protocols and intensive ecological studies. SHA
      probes have been instrumental in some of these efforts, as the technique performs
      well in complex heterogeneous sample matrices and has been adapted to benchtop
      and deployable (Environmental Sample Processor) platforms. The expanded probe set
      will enhance future efforts towards understanding spatial, temporal and
      successional patterns in species during bloom and non-bloom periods.

PMID- 29169568
TI  - Life-history stages of natural bloom populations and the bloom dynamics of a
      tropical Asian ribotype of Alexandrium minutum.
AB  - In 2015, a remarkably high density bloom of Alexandrium minutum occurred in
      Sungai Geting, a semi-enclosed lagoon situated in the northeast of Peninsular
      Malaysia, causing severe discoloration and contaminated the benthic clams
      (Polymesoda). Plankton and water samples were collected to investigate the
      mechanisms of bloom development of this toxic species. Analysis of bloom samples
      using flow cytometry indicated that the bloom was initiated by the process of
      active excystment, as planomycetes (>4C cells) were observed in the early stage
      of the bloom. Increase in planozygotes (2C cells) was evident during the middle
      stage of the bloom, coinciding with an abrupt decrease in salinity and increase
      of temperature. The bloom was sustained through the combination of binary
      division of vegetative cells, division of planozygotes, and cyst germination
      through continuous excystment. Nutrient depletion followed by precipitation
      subsequently caused the bloom to terminate. This study provides the first
      continuous record of in situ life-cycle stages of a natural bloom population of
      A. minutum through a complete bloom cycle. The event has provided a fundamental
      understanding of the pelagic life-cycle stages of this tropical dinoflagellate,
      and demonstrated a unique bloom development characteristic shared among toxic
      Alexandrium species in coastal embayments.

PMID- 29169569
TI  - Effects of modified clay on the physiological and photosynthetic activities of
      Amphidinium carterae Hulburt.
AB  - Among the strategies for treating harmful algal blooms, flocculation using
      modified clay (MC) has been widely applied in the field. This paper studied the
      mitigation of MC on Amphidinium carterae Hulburt, finding that MC could not only
      effectively remove A. carterae, but also affect the physiological activities of
      the residual algae and inhibit their normal growth. The superoxide dismutase
      (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) content of the
      residual algae significantly increased compared with the control, indicating that
      MC stimulated the accumulation of reactive oxygen species (ROS) in algal cells.
      In addition, the cell density was significantly correlated with the SOD activity,
      CAT activity and MDA content in the experiment groups, suggesting that
      intracellular ROS might be the main internal factor inhibiting cell growth. To
      reveal the mechanism of ROS generation, this paper further evaluated the effect
      of MC on photosynthesis in the residual microalgae, and found that compared with
      the control the absorption flux per photosystem II (PSII) reaction center
      (ABS/RC), the trapping flux per RC (TR0/RC) and the electron transport flux per
      RC (ET0/RC) increased, while the TR0/ABS and ET0/ABS decreased after adding
      0.10g/L and 0.25g/L MC. These findings indicate that the MC led to an imbalance
      between photosynthetic light absorption and energy utilization and that the
      partial RCs became non-primary quinone electron acceptor (QA)-RCs, further
      inducing the over-excitation of the active RCs. And MC caused the suppression of
      the electron transport chain (ETC): the ETC from the QA to the secondary quinone
      electron acceptor (QB) was blocked and the size of plastoquinone pool decreased,
      which could induce the over-reduction of PSII. The over-excitation of PSII and
      the damaged ETC likely induce the generation of ROS during photosynthesis. Thus,
      MC likely induced the accumulation of intracellular ROS due to photosynthesis
      inhibition, consequently hindering the growth of the residual algae.

PMID- 29169571
TI  - Differences in the photoacclimation and photoprotection exhibited by two species
      of the ciguatera causing dinoflagellate genus, Gambierdiscus.
AB  - In culture, Gambierdiscus spp. have been shown to prefer irradiances that are
      relatively low (<=250MUmol photonsm-2s-1) versus those to which they are
      frequently exposed to in their natural environment (>500MUmol photonsm-2s-1).
      Although several behavioral strategies for coping with such irradiances have been
      suggested, it is unclear as to how these dinoflagellates do so on a physiological
      level. More specifically, how do long term exposures (30days) affect cell size
      and cellular chlorophyll content, and what is the photosynthetic response to
      short term, high irradiance exposures (up to 1464MUmol photonsm-2s-1)? The
      results of this study reveal that cell size and chlorophyll content exhibited by
      G. carolinianus increased with acclimation to increasing photon flux density.
      Additionally, both G. carolinianus and G. silvae exhibited reduced photosynthetic
      efficiency when acclimated to increased photon flux density. Photosynthetic yield
      exhibited by G. silvae was greater than that for G. carolinianus across all
      acclimation irradiances. Although such differences were evident, both G.
      carolinianus and G. silvae appear to have adequate biochemical mechanisms to
      withstand exposure to irradiances exceeding 250MUmol photonsm-2s-1 for at least
      short periods of time following acclimation to irradiances of up to 150MUmol
      photonsm-2s-1.

PMID- 29169570
TI  - Morphology and phylogeny of Prorocentrum caipirignum sp. nov. (Dinophyceae), a
      new tropical toxic benthic dinoflagellate.
AB  - A new species of toxic benthic dinoflagellate is described based on laboratory
      cultures isolated from two locations from Brazil, Rio de Janeiro and Bahia. The
      morphology was studied with SEM and LM. Cells are elliptical in right thecal view
      and flat. They are 37-44MUm long and 29-36MUm wide. The right thecal plate has a
      V shaped indentation where six platelets can be identified. The thecal surface of
      both thecal plates is smooth and has round or kidney shaped and uniformly
      distributed pores except in the central area of the cell, and a line of marginal
      pores. Some cells present an elongated depression on the central area of the
      apical part of the right thecal plate. Prorocentrum caipirignum is similar to
      Prorocentrum lima in its morphology, but can be differentiated by the general
      cell shape, being elliptical while P. lima is ovoid. In the phylogenetic trees
      based on ITS and LSU rDNA sequences, the P. caipirignum clade appears close to
      the clades of P. lima and Prorocentrum hoffmannianum. The Brazilian strains of P.
      caipirignum formed a clade with strains from Cuba, Hainan Island and Malaysia and
      it is therefore likely that this new species has a broad tropical distribution.
      Prorocentrum caipirignum is a toxic species that produces okadaic acid and the
      fast acting toxin prorocentrolide.

PMID- 29169572
TI  - Opportunistic salpingectomy in women undergoing hysterectomy: Results from the
      HYSTUB randomised controlled trial.
AB  - OBJECTIVE: To evaluate whether opportunistic salpingectomy in premenopausal women
      undergoing hysterectomy for benign indications is both hormonally and surgically
      safe, compared with hysterectomy without salpingectomy. STUDY DESIGN: In this
      multicentre randomised controlled trial, women were randomised to undergo either
      hysterectomy with opportunistic bilateral salpingectomy (intervention group) or
      standard hysterectomy with preservation of the Fallopian tubes (control group).
      MAIN OUTCOME MEASURES: The primary outcome was the difference in serum anti
      Mullerian hormone concentration (DeltaAMH), measured pre-surgery and 6 months
      post-surgery. Secondary outcomes were surgical outcomes and duration of hospital
      stay. The sample size was powered at 50 participants per group (n=100) to compare
      DeltaAMH after hysterectomy with salpingectomy to DeltaAMH after standard
      hysterectomy. RESULTS: Between March 2013 and December 2016, 104 women, aged 30
      55 years, were randomly allocated to hysterectomy with opportunistic bilateral
      salpingectomy (n=52) or standard hysterectomy (n=52). The baseline
      characteristics did not differ between the two groups. The median DeltaAMH was 
      0.14pmol/L (IQR -1.47-0.95) in the intervention group and 0.00pmol/L (IQR -1.05
      0.80) in the control group (p=0.49). The addition of salpingectomy did not impair
      surgical results and it did not affect duration of hospital stay. CONCLUSION:
      Addition of opportunistic bilateral salpingectomy during hysterectomy did not
      result in a larger effect on ovarian reserve when compared with hysterectomy
      alone, neither did it affect surgical outcomes. Therefore, opportunistic
      salpingectomy seems to be a safe procedure in premenopausal women undergoing
      hysterectomy for benign gynaecological conditions.

PMID- 29169573
TI  - Choosing a medication brand: Excipients, food intolerance and prescribing in
      older people.
AB  - Multiple brands of the same active ingredient may be available for the same
      strength, administration route and dose form. Generic brands needs to demonstrate
      bioequivalence to the originator brand, but the appearance of the generic and
      originator brands are not required to match. This variation is possible because
      different brands may vary in the excipients used in the formulation. Excipients
      are inactive ingredients, and typically make up about 90% of the formulation of
      an individual medication. Individual preferences or requirements may affect
      tolerance of particular excipients, such as the use of animal products. The
      different appearance of brands can affect medication management for some people.
      This review discusses the potential for excipients to alter the individual
      response to or tolerance of a medication brand.

PMID- 29169574
TI  - The male-female health-survival paradox in hospitalised older adults.
AB  - OBJECTIVES: To determine whether the 'male-female health-survival paradox' is
      present in older hospitalised adults and to examine whether sex differences in
      the 'lethality' of acute medical conditions influence the relationship between
      sex and mortality. STUDY DESIGN AND OUTCOME MEASURES: This study was a secondary
      analysis of prospective cohort data collected from 1418 Australian inpatients
      aged 70 years and over. Frailty was measured using a 39-variable Frailty Index
      (FI-AC). Analyses examined the relationship between sex, age, FI-AC and 28-day
      mortality. Survival models were adjusted for 'lethality' of acute conditions
      (high versus low mortality risk). RESULTS: The FI-AC had a normal distribution in
      both sexes (female mean=0.34 (+/-0.13); male mean=0.31 (+/-0.15)). When adjusted
      for age, females had similar FI-AC scores to males (beta coefficient=0.014, 95%
      confidence interval (CI)=0.00-0.028, p=0.056). There were 80 deaths in the
      sample, with females facing a significantly lower mortality risk than males of
      the same FI-AC and age (HR=0.39, 95% CI=0.25-0.63, p<0.001). Females were less
      likely than males to be admitted with a high-risk acute condition. Even so, this
      did not significantly reduce their survival advantage (HR=0.46, 95% CI=0.29-0.73,
      p=0.001). CONCLUSION: The male-female health-survival paradox was not
      demonstrated in this study of older inpatients. Whilst females faced a
      significantly lower risk of near-term mortality, the sexes were found to have
      similar levels of frailty on admission to hospital. The sex mortality gap was not
      explained by sex differences in the 'lethality' of acute medical conditions.

PMID- 29169575
TI  - Health determinants and survival in nursing home residents in Europe: Results
      from the SHELTER study.
AB  - OBJECTIVE: The care processes directed towards institutionalized older people
      needs to be tailored on goals and priorities that are relevant for this specific
      population. The aim of the present study was (a) to describe the distribution of
      selected health determinants in a sample of institutionalized older adults, and
      (b) to investigate the impact on survival of such measures. DESIGN: Multicentre
      longitudinal cohort-study. SETTING: 57 nursing homes (NH) in 7EU countries (Czech
      Republic, England, Finland, France, Germany, Italy, The Netherlands) and 1 non-EU
      country (Israel). PARTICIPANTS: 3036 NH residents participating in the Services
      and Health for Elderly in Long TERm care (SHELTER) study. MEASUREMENTS: We
      described the distribution of 8 health determinants (smoking habit, alcohol use,
      body mass index [BMI], physical activity, social participation, family visits,
      vaccination, and preventive visits) and their impact on 1-year mortality.
      RESULTS: During the one-year follow up, 611 (20%) participants died. Overweight
      (HR 0.79; 95% C.I. 0.64-0.97) and obesity (HR 0.64; 95% C.I. 0.48-0.87) resulted
      associated with lower mortality then normal weight. Similarly, physical activity
      (HR 0.67; 95% C.I. 0.54-0.83), social activities (HR 0.63; 95% C.I. 0.51-0.78),
      influenza vaccination (HR 0.66; 95% C.I. 0.55-0.80) and pneumococcal vaccination
      (HR 0.76 95% C.I. 0.63-0.93) were associated with lower mortality. Conversely,
      underweight (HR 1.28; 95% C.I. 1.03-1.60) and frequent family visits (HR 1.75;
      95% C.I. 1.27-2.42) were associated with higher mortality. CONCLUSIONS: Health
      determinants in older NH residents depart from those usually accounted for in
      younger and fitter populations. Ad hoc studies are warranted in order to describe
      other relevant aspects of health in frail older adults, with special attention on
      those institutionalized, with the ultimate goal of improving the quality of care
      and life.

PMID- 29169576
TI  - Sarcopenia and sarcopenic obesity in Spanish community-dwelling middle-aged and
      older women: Association with balance confidence, fear of falling and fall risk.
AB  - OBJECTIVES: To analyze the association of sarcopenia, obesity, and sarcopenic
      obesity (SO) with fear of falling (FoF) and balance confidence in a Spanish
      sample of middle-aged and older community-dwelling women. STUDY DESIGN AND
      OUTCOME MEASURES: A total of 235 women (69.21+/-7.56 years) participated in this
      study. Body composition (bioelectrical impedance analysis), hand-grip strength,
      and physical performance (gait speed) were evaluated for the diagnosis of
      sarcopenia, obesity, and SO. Anxiety and depression were measured using the
      Hospital Anxiety and Depression Scale. The Activities-Specific Balance Confidence
      Scale (ABC) and the Falls Efficacy Scale-International (FES-I) were employed to
      assess FoF and balance confidence, respectively. Scores of >26 on the FES-I and
      <67% on the ABC were used to identify women at risk of falling. The independent
      associations of sarcopenia, obesity and SO with FoF, balance confidence, and fall
      risk were evaluated by multivariate linear and logistic regressions, adjusting
      for potential confounding variables. RESULTS: 27.23% and 18.72% of women
      presented with sarcopenia and SO, respectively. Gait speed, body mass index
      (BMI), and fall history were independently associated with ABC score (adjusted
      R2=0.152) and fall risk (ABC) (adjusted-R2=0.115). FES-I score was independently
      associated (adjusted-R2=0.193) with fall history, gait speed, BMI, and
      depression, which, together with obesity (BMI) and SO, remained independent
      factors for fall risk measured as FES-I score (adjusted-R2=0.243). CONCLUSION: In
      community-dwelling middle-aged and older Spanish women, BMI, gait speed, and fall
      history were independently associated with FoF, balance confidence, and fall
      risk. Depression was related only to FoF, and, together with obesity (BMI) and
      SO, was an independent predictor of fall risk as assessed by the FES-I.

PMID- 29169578
TI  - Post-hysterectomy vaginal vault prolapse.
AB  - Post-hysterectomy vaginal vault prolapse (PHVP) is a recognised although rare
      complication following both abdominal and vaginal hysterectomy and the risk is
      increased in women following vaginal surgery for urogenital prolapse. The
      management of PHVP remains challenging and whilst many women will initially
      benefit from conservative measures, the majority will ultimately require surgery.
      The purpose of this paper is to review the prevalence and risk factors associated
      with PHVP as well to give an overview of the clinical management of this often
      complicated problem. The role of prophylactic primary prevention procedures at
      the time of hysterectomy will be discussed as well as initial conservative
      management. Surgery, however, remains integral in managing these complex patients
      and the vaginal and abdominal approach to managing PHVP will be reviewed in
      detail, in addition to both laparoscopic and robotic approaches.

PMID- 29169577
TI  - Excess fat in the abdomen but not general obesity is associated with poorer
      metabolic and cardiovascular health in premenopausal and postmenopausal Asian
      women.
AB  - OBJECTIVES: To examine the associations of various metabolites and hormones and
      hormone replacement therapy (HRT) with obesity. METHODS: This is a cross
      sectional study of 1326 Singaporean women. A DXA-derived percent body fat (PBF)
      of >=35% and percent abdominal fat (PAbdF) of >21.8% were used, respectively, to
      define women with general (GOb) and abdominal (AbdOb) obesity. RESULTS: Higher
      levels of insulin and glucose, lower levels of HDL, higher levels of TC/HDL and
      HOMA values, and different levels of some hormones were noted only in the women
      with abdominal, and not general obesity. The incidence of general and abdominal
      obesity was higher in postmenopausal women with or without HRT, except that those
      who were on conjugated estradiol-only HRT had no increase in the incidence of
      general obesity compared with premenopausal women. CONCLUSIONS: Abdominal obesity
      is associated with insulin resistance and with higher risks of metabolic syndrome
      and cardiovascular diseases, whereas general obesity is not. Abdominal obesity
      may predispose to a higher risk of diabetes. The onset of the menopause tends to
      increase the incidence of general and abdominal obesity, except that
      postmenopausal women on conjugated estradiol HRT appear to be relatively
      protected from general obesity.

PMID- 29169579
TI  - Data Registry on Experiences of Aging, Menopause, and Sexuality (DREAMS): A
      cohort profile.
AB  - The Women's Health Clinic (WHC) at Mayo Clinic in Rochester, Minnesota, has
      provided consultative care to women with menopausal and sexual health concerns
      since 2005. Clinical information on the 8688 women seen in the WHC through May
      2017 who gave consent for the use of their medical records in research is
      contained in the Data Registry on Experiences of Aging, Menopause, and Sexuality
      (DREAMS). Initially, DREAMS was created to improve the clinical care of women,
      but it has become a valuable research tool. About 25% of the DREAMS women have
      been seen in the WHC 2 or more times, allowing for passive longitudinal follow
      up. Additionally, about 25% of the DREAMS women live in the 27-county region
      included in the expanded Rochester Epidemiology Project medical records linkage
      system, providing additional information on those women. The cohort has been used
      to investigate associations between: caffeine intake and vasomotor symptom
      bother; recent abuse (physical, sexual, verbal, and emotional) and menopausal
      symptoms; specific menopausal symptoms and self-reported view of menopause; and
      obstructive sleep apnea risk and vasomotor symptom severity and the experience of
      vasomotor symptoms in women older than 60 years. A study nearing completion
      describes a clinical series of over 3500 women presenting for sexual health
      consultation by sexual function domain and by decade of life. Other studies under
      way are determining correlates with sexual health and dysfunction. Planned
      studies will investigate associations between the experience with menopause and
      the risk of disease.

PMID- 29169580
TI  - The effects of frailty and cognitive impairment on 3-year mortality in older
      adults.
AB  - OBJECTIVES: Frailty and cognitive impairment in late life increase the risk of
      mortality. Physical frailty is closely associated with cognitive impairment. The
      aim of the study was to examine the independent and interaction effects of
      frailty and cognitive impairment in predicting mortality. STUDY DESIGN: A
      nationally representative sample of community-dwelling Koreans aged 65 years and
      older (n=11,266) was followed for 3 years. MAIN OUTCOME MEASURES: Frailty was
      categorized using Fried's phenotype model. Cognitive impairment was defined as
      more than 1.5 standard deviations below the age-, gender-, and education-specific
      norm of the Mini-Mental State Examination. Cox proportional hazards regression
      was used to analyze the mortality risk by frailty status and the moderating
      effect of cognitive impairment. RESULTS: Frailty was associated with cognitive
      impairment, with 922 (19.1%), 1609 (28.1%), and 392 (42.8%) of the nonfrail,
      prefrail, and frail group, respectively, being cognitively impaired. Compared
      with the nonfrail group, those who were prefrail (hazard ratio [HR]=1.38; 95%
      confidence interval [CI]: 1.10, 1.73) and frail (HR=1.78, 95% CI: 1.29, 2.46) had
      higher mortality rates, after adjusting for sociodemographic variables, health
      behaviors, and chronic conditions. Cognitive impairment was associated with a 30%
      increased mortality rate. A significant interaction between frailty and cognitive
      impairment was observed (p=0.003). Compared with those nonfrail and not
      cognitively impaired, frail persons with cognitive impairment had a lower
      survival rate (HR=1.92, 95% CI: 1.26, 2.93). CONCLUSIONS: Frailty was a
      significant predictor of 3-year mortality in community-dwelling older adults,
      with the association being moderated by baseline cognitive status. Taking
      cognitive function into account may allow better prediction of adverse outcomes
      of frailty in later life.

PMID- 29169581
TI  - Vitamin D status is associated with executive function a decade later: Data from
      the Women's Healthy Ageing Project.
AB  - OBJECTIVES: Vitamin D deficiency has been associated with cognitive decline and
      dementia in older adults. However, there is a paucity of studies assessing
      whether this association manifests from midlife. Given the long prodromal stage
      of dementia, we investigated the association between midlife vitamin D and
      cognition 10 years later. STUDY DESIGN: 252 participants (aged 55-67 years) from
      the Women's Healthy Ageing Project had baseline (2002) vitamin D and
      neuropsychological measures assessed. Of these, 170 (aged 65-77 years) had follow
      up neuropsychological testing (2012). OUTCOME MEASURES: Serum 25-hydroxyvitamin D
      (25[OH]D) was measured using an automated chemiluminescence system. The
      neuropsychological tests used were: Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD), California Verbal Learning Test Second Edition (CVLT
      II), verbal fluency and Trail Making Test-B (TMT-B). Composite scores for verbal
      episodic memory (CERAD and CVLT-II) and executive function (verbal fluency and
      TMT-B) were obtained by summating standardized scores for each test. RESULTS:
      Analyses were adjusted for age, education and body mass index (BMI). Further
      adjustment for physical activity, depression, vascular risk factors,
      supplementation and APOE4-genotype did not materially change the results. At
      baseline, those with vitamin D>25nmol/L performed better on verbal fluency
      (beta=2.46, 95%CI=0.53,4.40) and TMT-B time (beta=-18.23, 95%CI=-32.86,-3.61),
      with higher executive function (beta=1.40, 95%CI=0.44,2.37). These relationships
      persisted 10 years later for TMT-B (beta=-15.38, 95%CI=-30.82,0.07) and executive
      function (beta=1.05, 95%CI=0.14,1.95). There were no associations with tests of
      verbal episodic memory. CONCLUSION: Midlife vitamin D>25nmol/L is associated with
      improved aspects of executive function in ageing. Findings highlight a potential
      therapeutic age window where midlife vitamin D repletion could be neuroprotective
      against cognitive decline.

PMID- 29169582
TI  - History of cervical insufficiency increases the risk of pelvic organ prolapse and
      stress urinary incontinence in parous women.
AB  - OBJECTIVE: A likely contributor to pelvic floor disorders is injury and
      degradation of connective tissue components such as collagen and elastin, leading
      to weakening of the pelvic floor. Prior studies have found similar connective
      tissue component changes in women with cervical insufficiency (CI). However, the
      connection between pelvic floor disorders and cervical insufficiency has not
      previously been evaluated. Our objective was to determine whether a history of
      cervical insufficiency is associated with an increased risk of pelvic organ
      prolapse and stress urinary incontinence after controlling for confounders. STUDY
      DESIGN: The study used de-identified clinical data from a large multi-institution
      electronic health records HIPAA-compliant data web application, Explorys Inc.
      (Cleveland, Ohio, USA). Women with a history of at least one prior delivery after
      at least 20 weeks' gestation between the years 1999 and 2016 were identified.
      Logistic regression models were used to identify risk factors and adjust for
      confounders. MAIN OUTCOME MEASURES: The primary outcome was subsequent
      development of either stress incontinence or pelvic organ prolapse. RESULTS: A
      total of 1,182,650 women were identified, of whom 30,890 (2.6%) had a history of
      cervical cerclage or insufficiency. A history of cervical insufficiency was
      associated with an increased risk of either pelvic organ prolapse or stress
      urinary incontinence (aOR=1.93, 95%CI: 1.84-2.02). A history of cervical
      insufficiency was more strongly associated with an increased risk of pelvic organ
      prolapse (aOR=2.06, 95%CI: 1.91-2.21) than with stress urinary incontinence
      (aOR=1.91, 95%CI: 1.80-2.02). CONCLUSION: A history of cervical insufficiency is
      associated with an increased risk of development of pelvic organ prolapse and
      stress urinary incontinence.

PMID- 29169583
TI  - Gender-specific associations between quality of life and leukocyte telomere
      length.
AB  - We conducted a study on the relationship between leukocyte telomere length (LTL)
      and quality of life (QoL) in 82 couples aged 55 and older. LTL was measured by
      quantitative real-time PCR. QoL was evaluated using the physical component score
      (PCS) and mental component score (MCS) on the Korean version of the Short-Form
      Health Survey (SF-36). LTL was found to be independently associated with the SF
      36 PCS in males (beta=0.014, p=0.03) and the SF-36 MCS in females (beta=1.16,
      p<0.01). Thus LTL is associated with QoL in gender-specific ways.

PMID- 29169584
TI  - Calcium in the prevention of postmenopausal osteoporosis: EMAS clinical guide.
AB  - INTRODUCTION: Postmenopausal osteoporosis is a highly prevalent disease.
      Prevention through lifestyle measures includes an adequate calcium intake.
      Despite the guidance provided by scientific societies and governmental bodies
      worldwide, many issues remain unresolved. AIMS: To provide evidence regarding the
      impact of calcium intake on the prevention of postmenopausal osteoporosis and
      critically appraise current guidelines. MATERIALS AND METHODS: Literature review
      and consensus of expert opinion. RESULTS AND CONCLUSION: The recommended daily
      intake of calcium varies between 700 and 1200mg of elemental calcium, depending
      on the endorsing source. Although calcium can be derived either from the diet or
      supplements, the former source is preferred. Intake below the recommended amount
      may increase fragility fracture risk; however, there is no consistent evidence
      that calcium supplementation at, or above, recommended levels reduces risk. The
      addition of vitamin D may minimally reduce fractures, mainly among
      institutionalised people. Excessive intake of calcium, defined as higher than
      2000mg/day, can be potentially harmful. Some studies demonstrated harm even at
      lower dosages. An increased risk for cardiovascular events, urolithiasis and even
      fractures has been found in association with excessive calcium intake, but this
      issue remains unresolved. In conclusion, an adequate intake of calcium is
      recommended for general bone health. Excessive calcium intake seems of no
      benefit, and could possibly be harmful.

PMID- 29169585
TI  - Socio-economic indicators and diet quality in an older population.
AB  - PURPOSE: To examine the strength and independence of associations between three
      major socio-economic indicators (income, education and occupation) and diet
      quality (DQ) at baseline and after 20-year follow-up. METHODS: Cross-sectional
      and longitudinal analyses using data collected in the Rotterdam Study, a
      prospective population-based cohort. Participants were categorised according to
      socio-economic indicators (education, occupation and household income) measured
      at baseline (1989-1993). Participants aged 55 years or older were included
      (n=5434). DQ was assessed at baseline (1989-1993) and after 20 years (2009-2011)
      and quantified using the Dutch Healthy Diet Index, reflecting adherence to the
      Dutch guidelines for a healthy diet; scores can range from 0 (no adherence) to 80
      (optimal adherence). Linear regression models were adjusted for sex, age, smoking
      status, BMI, physical activity level, total energy intake and mutually adjusted
      for the other socio-economic indicators. RESULTS: At baseline, scores on the
      Dutch Healthy Diet Index were 2.29 points higher for participants with the
      highest level of education than for those with the lowest level (95%CI=1.23
      3.36); in addition, they were more likely to have a higher DQ at follow-up
      (beta=3.10, 95%CI=0.71-5.50), after adjustment for baseline DQ. In contrast,
      higher income was associated with lower DQ at follow-up (beta=-1.92, 95%CI=-3.67,
      -0.17), whereas occupational status was not associated with DQ at baseline or at
      follow-up. CONCLUSION: In our cohort of Dutch participants, a high level of
      education was the most pronounced socio-economic indicator of high DQ at baseline
      and at follow-up. Our results highlight that different socio-economic indicators
      influence DQ in different ways.

PMID- 29169586
TI  - The prevalence of urinary incontinence in nulliparous adolescent and middle-aged
      women and the associated risk factors: A systematic review.
AB  - Urinary incontinence (UI) has been defined as the complaint of involuntary loss
      of urine. There is a general belief that UI is experienced almost exclusively by
      the elderly and women who have given birth. However, epidemiological studies
      report that young women who are nulliparous also experience UI. The aim of this
      study was to systematically review studies investigating the prevalence of UI in
      nulliparous adolescent and middle-aged women and to provide an overview of risk
      factors associated with UI. The electronic databases PubMed, EMBASE, CINAHL, and
      Cochrane Library were systematically searched for eligible studies. Inclusion and
      exclusion criteria were defined a priori. The selected studies were reviewed and
      data extraction was carried out by the reviewers. Two independent researchers
      assessed the quality of the included studies. Eighteen studies were included in
      this systematic review. UI prevalence estimates varied from 1% to 42.2%. Among
      the women with UI of any type, 12.5% to 79% had stress urinary incontinence. BMI,
      childhood enuresis, and high-impact exercising were found to be the main
      associated risk factors. Understanding the effect of the risk factors on the
      pelvic floor will enable us to implement preventive strategies and advise
      appropriately on the prevention of UI.

PMID- 29169587
TI  - Multimorbidity and perceived stress: a population-based cross-sectional study
      among older adults across six low- and middle-income countries.
AB  - BACKGROUND: Stress in chronic conditions or multimorbidity (>=2 chronic
      conditions) has been reported to affect clinical outcomes but there are no
      studies on the association between stress and chronic conditions/multimorbidity
      among older adults in low- and middle-income countries (LMICs). Thus, we
      investigated this association among adults aged >=50 years across six LMICs.
      METHODS: A cross-sectional analysis using data from the World Health
      Organization's Study on Global Ageing and Adult Health (China, Ghana, India,
      Mexico, Russia, South Africa) was conducted. A perceived stress score [range 0
      (lowest stress) -100 (highest stress)] was computed based on two questions from
      the Perceived Stress Scale. Thirteen chronic conditions were assessed.
      Multivariable linear regression analyses were conducted. RESULTS: 34,129 adults
      with a mean age of 62.4 (SD=16.0)years (52.1% females) were included. Overall,
      56.6% (95% CI=55.0%-58.2%) had multimorbidity. In the adjusted model including
      all countries, compared with those with no chronic conditions, higher numbers of
      chronic conditions were significantly associated with higher stress levels, dose
      dependently. In a countrywide meta-analysis, multimorbidity was associated with
      significantly higher stress levels in all countries (especially India and Ghana)
      although characterized by moderate heterogeneity (I2=54.6%). For single chronic
      conditions, notably high stress scores were observed for depression, stroke, and
      hearing problems. CONCLUSION: Chronic conditions and multimorbidity are
      associated with higher levels of stress in older adults in LMICs. Given that
      perceived stress and chronic conditions are collectively associated with worse
      health outcomes, low-cost, population-level integrated interventions to address
      stress among those with chronic conditions are urgently needed.

PMID- 29169588
TI  - Changes in hormonal and metabolic parameters in transgender subjects on cross-sex
      hormone therapy: A cohort study.
AB  - OBJECTIVES: Gender identity disorder is defined as a strong and persistent cross
      gender identification that is associated with a remarkable uneasiness of living
      in an incongruent gender (gender dysphoria). We performed a retrospective study
      on the hormonal and metabolic effects of cross-sex hormone therapy (CSHT) in a
      small cohort of transgender patients. STUDY DESIGN: Retrospective study. MEAN
      OUTCOME MEASURES: Hormonal and biochemical parameters at baseline (i.e. before
      commencement of CSHT) and while on CSHT in 32 patients (21 male to female [MtF],
      11 female to male [FtM]) referred to our Endocrinology Unit for gender dysphoria
      between January 2012 and February 2017. RESULTS: Compared with baseline, in MtF
      patients systolic blood pressure, red cell count, hemoglobin, hematocrit and
      total testosterone decreased significantly, while 17-beta estradiol and SHBG
      increased significantly and trendwise significantly, respectively. In FtM
      patients, total testosterone, red cell count, hemoglobin, hematocrit, creatinine,
      gamma-glutamyl transferase and alkaline phosphatase increased significantly,
      while fasting plasma glucose decreased trendwise significantly. In MtF patients
      17-beta estradiol correlated positively with SHBG and alkaline phosphatase and
      negatively with total cholesterol and HDL-c, whereas total testosterone
      correlated positively with systolic blood pressure, red cell count and
      hematocrit, and negatively with SHBG. In FtM patients total testosterone
      correlated positively with creatinine and alkaline phosphatase, while 17-beta
      estradiol correlated positively with HDL-c. CONCLUSIONS: Our data are partly in
      line with other studies concerning the impact of CSHT on hormonal and metabolic
      parameters in transgender people. Metabolic changes appear, overall, to be
      modest, confirming the safety of CSHT.

PMID- 29169589
TI  - Vitamin D deficiency is associated with metabolic syndrome in postmenopausal
      women.
AB  - OBJECTIVE: To evaluate the association between vitamin D (VD) deficiency and risk
      factors for metabolic syndrome (MetS) in postmenopausal women. STUDY DESIGN:
      Observational, cross-sectional cohort study. MAIN OUTCOME MEASURES: In this
      study, 463 women, aged 45-75 years, with amenorrhea >12months, without VD
      supplementation or established cardiovascular disease were included. Clinical and
      anthropometric data were collected. Biochemical parameters, including total
      cholesterol (TC), HDL, LDL, triglycerides, glucose, insulin and 25-hydroxyvitamin
      D [25(OH)D] were measured. Women meeting three or more of the following criteria
      were diagnosed with MetS: waist circumference >88cm, triglycerides >=150mg/dL,
      HDL <50mg/dL, blood pressure >=130/85mmHg and glucose >=100mg/dL. Serum 25(OH)D
      levels were classified as sufficient (>=30ng/mL), insufficient (20-29ng/mL) or
      deficient (<20ng/mL). ANOVA, chi-square test and logistic regression (odds ratio,
      OR) were used for statistical analysis. RESULTS: Serum 25(OH)D levels were
      sufficient in 148 women (32.0%), insufficient in 151 (32.6%) and deficient in 164
      (35.4%). Women with low 25(OH)D levels had higher TC, triglycerides, insulin and
      HOMA-IR levels (p<0.05). MetS was detected in 57.8% (182/315) of women with
      hypovitaminosis D (insufficient and deficient) and in 39.8% (59/148) of those
      with sufficient VD (p=0.003). In a multivariate logistic regression analysis, a
      low 25(OH)D level (<30ng/mL) was significantly associated with MetS (OR1.90,
      95%CI=1.26-2.85), high triglyceride levels (OR1.55, 95%CI=1.13-2.35), and low HDL
      levels (OR1.60, 95%CI=1.19-2.40) (p<0.05) compared with women with sufficient
      25(OH)D levels, after adjusting for age, time since menopause, body mass index,
      smoking and physical exercise. The mean concentration of 25(OH)D decreased with
      increasing numbers of MetS components (p=0.016). CONCLUSIONS: VD deficiency in
      postmenopausal women was associated with a higher prevalence of MetS. Women with
      VD deficiency had a higher risk of MetS, hypertriglyceridemia and low HDL than
      those with adequate levels.

PMID- 29169590
TI  - Open Fractures of the Hand: Review of Pathogenesis and Introduction of a New
      Classification System.
AB  - Open fractures of the hand are a common and varied group of injuries. Although at
      increased risk for infection, open fractures of the hand are more resistant to
      infection than other open fractures. Numerous unique factors in the hand may play
      a role in the altered risk of postinjury infection. Current systems for the
      classification of open fractures fail to address the unique qualities of the
      hand. This article proposes a novel classification system for open fractures of
      the hand, taking into account the factors unique to the hand that affect its risk
      for developing infection after an open fracture.

PMID- 29169591
TI  - Radial Nerve Palsy After Humeral Shaft Fractures: The Case for Early Exploration
      and a New Classification to Guide Treatment and Prognosis.
AB  - Radial nerve palsies are a common complication associated with humeral shaft
      fractures. The authors propose classifying these injuries into 4 types based on
      intraoperative findings: type 1 stretch/neuropraxia, type 2 incarcerated, type 3
      partial transection, and type 4 complete transection. The initial management of
      radial nerve palsies associated with closed fractures of the humerus remains a
      controversial topic, with early exploration reserved for open fractures,
      fractures that cannot achieve an adequate closed reduction requiring fracture
      repair, fractures with associated vascular injuries, and polytrauma patients.
      Outside of these recommendations, expectant observation for spontaneous recovery
      is recommended.

PMID- 29169592
TI  - Distal Radius Fractures in a Functional Quadruped: Spanning Bridge Plate Fixation
      of the Wrist.
AB  - Patients who require assistive devices with their hands for mobilization are
      called functional quadrupeds. These patients pose a unique challenge after they
      have a distal radius fracture, as their injury not only limits the wrist but also
      compromises ambulation. The authors propose a different treatment strategy for
      functional quadrupeds to improve mobilization and weight-bearing with the injured
      limb after a distal radius fracture. In this article, the authors define the
      functional quadruped and describe their technique of spanning bridge plate
      fixation with a retrospective review of patient outcomes.

PMID- 29169593
TI  - "Damage Control" Hand Surgery: Evaluation and Emergency Management of the Mangled
      Hand.
AB  - Mangled hand injuries are defined as those with significant damage to multiple
      structures, which may be limb threatening. Historically these injuries resulted
      in amputation or death, but modern surgical and perioperative advances allow for
      complex reconstruction and the possibility of a sensate and functional limb.
      Evaluation begins with surveying for life-threatening injuries followed by a
      systematic approach to identify injured structures; management begins with
      preserving all parts, minimizing warm ischemia time, performing debridement, and
      planning an operative approach to optimize the chance of a functional limb. With
      careful surgical planning and a well-executed reconstruction, most limbs can be
      salvaged.

PMID- 29169594
TI  - Carpal Tunnel Syndrome and Distal Radius Fractures.
AB  - Carpal tunnel syndrome (CTS) after distal radius fractures can present in 3
      forms: acute, transient, and delayed. Acute CTS requires an emergent carpal
      tunnel release. Many patients with transient CTS after distal radius fracture do
      not require surgical release of the carpal tunnel once the fracture is repaired.
      Prophylactic carpal tunnel release in the absence of signs and symptoms of CTS
      after a distal radius fracture is not indicated. For patients with delayed CTS
      after a distal radius fracture, all possible causes of nerve compression should
      be considered and addressed in standard fashion.

PMID- 29169595
TI  - Open Distal Radius Fractures: Timing and Strategies for Surgical Management.
AB  - Open distal radius fractures are rare injuries with few studies to guide
      treatment. Degree of soft tissue injury and contamination may be a primary
      consideration to dictate timing and operative intervention. Antibiotics should be
      started as early as possible and include a first-generation cephalosporin.
      Surgical fixation remains a matter of surgeon preference: although studies
      support the use of definitive internal fixation, many surgeons address
      contaminated injuries with external fixation. Although postoperative outcomes are
      similar to closed injuries for low-grade open distal radius fractures, high-grade
      injuries with more complex fracture patterns carry a high risk of complications,
      poor outcomes, and repeat surgical procedures.

PMID- 29169596
TI  - Hand Compartment Syndrome.
AB  - Acute hand compartment syndrome is a potentially devastating condition a hand
      surgeon may be called on to evaluate and treat. This pathophysiologic cascade of
      events that begins with an inciting event progresses to increased
      intracompartmental pressure, tissue necrosis, and resultant morbidity and
      potentially mortality. Many patients present with an altered sensorium, making
      the diagnosis challenging, requiring the clinician to rely on clinical findings
      and intracompartmental pressure measurements. The timing to definitive treatment
      with complete decompressive fasciotomies is critical to optimize patient
      outcomes. The goals of treatment are to prevent contracture, functional
      disability, and the loss of limb or life.

PMID- 29169597
TI  - Forearm Compartment Syndrome: Evaluation and Management.
AB  - Compartment syndrome of the forearm is uncommon but can have devastating
      consequences. Compartment syndrome is a result of osseofascial swelling leading
      to decreased tissue perfusion and tissue necrosis. There are numerous causes of
      forearm compartment syndrome and high clinical suspicion must be maintained to
      avoid permanent disability. The most widely recognized symptoms include pain out
      of proportion and pain with passive stretch of the wrist and digits. Early
      diagnosis and decompressive fasciotomy are essential in the treatment of forearm
      compartment syndrome. Closure of fasciotomy wounds can often be accomplished by
      primary closure but many patients require additional forms of soft tissue
      coverage procedures.

PMID- 29169598
TI  - Traumatic Wounds of the Upper Extremity: Coverage Strategies.
AB  - Soft tissue coverage of traumatic wounds of the upper extremity is often required
      to restore adequate function and form. An optimal coverage should be stable,
      durable, and able to withstand heavy demands of work, should allow free joint
      mobility, and should have an aesthetically acceptable appearance. Reconstructive
      options for coverage include autologous tissue and dermal skin substitutes.
      Multiple factors, including wound characteristics and complexity, general
      condition of the patient, and surgeon comfort and expertise, help in selection of
      the reconstructive technique. This article summarizes commonly used soft tissue
      reconstructive options for traumatic wounds of the upper extremity.

PMID- 29169599
TI  - Elbow Fractures with Instability: Evaluation and Treatment Strategies.
AB  - The treatment goals of elbow fracture dislocations are congruent reduction of the
      ulnohumeral and radiocapitellar joints, stable fixation of the proximal ulna,
      stable fixation or arthroplasty of the radial head, and soft tissue repair.
      Fracture dislocations occur in patterns, and recognition of these patterns help
      guide surgical treatment. In patients with persistently unstable fractures after
      standard fixation, additional temporary joint spanning implants are useful to
      protect repairs.

PMID- 29169600
TI  - Arterial Injury in the Upper Extremity: Evaluation, Strategies, and
      Anticoagulation Management.
AB  - Trauma to the upper extremity can present with an associated arterial injury.
      After patient stabilization, thorough assessment with physical examination and
      various imaging modalities allows accurate diagnosis of the specific arterial
      injury. After diagnosis, efficient treatment is necessary to allow limb salvage.
      Treatment options include ligation, primary repair, graft reconstruction,
      endovascular repair, and amputation. The final treatment rendered is frequently
      dependent on injury location and mechanism. With any of the treatment options,
      complications may occur, including thrombosis. Currently, no validated
      anticoagulation protocol has been established for managing arterial injuries in
      the upper extremity.

PMID- 29169601
TI  - Antibiotic Management and Operative Debridement in Open Fractures of the Hand and
      Upper Extremity: A Systematic Review.
AB  - Open fractures of the hand are thought to be less susceptible to infection than
      other open fractures because of the increased blood supply to the area. Current
      evidence for all open fractures shows that antibiotic use and the extent of
      contamination are predictive of infection risk, but time to debridement is not.
      We reviewed in a systematic review the available literature on open fractures of
      the hand and upper extremity to determine infection rates based on the timing of
      debridement and antibiotic administration. We continue to recommend prompt
      debridement and treatment of most open fractures of the upper extremity.

PMID- 29169602
TI  - Ulnar Nerve Management with Distal Humerus Fracture Fixation: A Meta-Analysis.
AB  - Ulnar nerve dysfunction following distal humerus fractures is a well-recognized
      phenomenon. There is no consensus regarding optimal handling of the ulnar nerve
      during surgical management of these fractures between in situ management and
      transposition. Using an electronic database to identify retrospective studies
      involving surgical fixation of distal humerus fractures yielded 46 studies, 5
      trials meeting the authors' inclusion criteria, totaling 362 patients. An overall
      incidence of 19.3% for ulnar neuropathy was identified. Of those patients
      undergoing in situ release, the incidence was 15.3%. Of those who underwent
      transposition, there was a 23.5% incidence of ulnar neuropathy.

PMID- 29169603
TI  - Complex Trauma Management of the Upper Extremity.

PMID- 29169604
TI  - Validation of Peripherally Inserted Central Catheter-Derived Fick Cardiac Outputs
      in Patients with Heart Failure.
AB  - The pulmonary artery catheter (PAC) remains the gold standard to calculate Fick
      cardiac outputs (FCOs) in patients with heart failure admitted to the intensive
      care unit (ICU). The peripherally inserted central catheter (PICC) provides long
      term intravenous access and is used outside the ICU; however, there is scant
      literature validating venous oxygen saturations (VOSs) from PICC lines. Heart
      failure patients in the ICU with an existing PAC requiring a PICC line to
      transition were enrolled. Three blood samples were taken per person (1 at PICC, 1
      at central venous pressure [CVP], and 1 at distal PAC). We performed repeated
      measures analysis of variance, as well as reliability analysis on 31 subjects
      (77% male, 71% Caucasian, mean +/- standard deviation age 60 +/- 8 years, 80% on
      inotropes). The average VOSs were 62 +/- 11%, 62 +/- 12%, and 61 +/- 9% for the
      PICC line, CVP, and distal port, respectively (p = 0.66); there was excellent
      reliability (0.79). The median FCOs were 5 [4, 6], 5 [4, 6], and 5 [4, 6] L/min
      at the PICC, CVP, and distal port, respectively (p = 0.91); there was fair-to
      good reliability (0.67). In conclusion, VOS and FCO did not differ by location,
      on average. Reliable data may be obtained through the PICC line, after evaluation
      from the PAC. The PICC may provide longer-term hemodynamic assessment while
      improving patient comfort.

PMID- 29169605
TI  - Relation of Stroke and Bleeding Risk Profiles to Efficacy and Safety of Edoxaban
      for Cardioversion of Atrial Fibrillation (from the EdoxabaN versus warfarin in
      subjectS UndeRgoing cardiovErsion of Atrial Fibrillation [ENSURE-AF] Study).
AB  - In the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial
      Fibrillation (ENSURE-AF) study, edoxaban was compared with enoxaparin-warfarin in
      patients who underwent electrical cardioversion of nonvalvular atrial
      fibrillation, showing comparable low rates of bleeding and thromboembolism. The
      present study is an ancillary analysis investigating differences in relation to
      stroke and bleeding risk profiles. It also determined the relation of patients'
      clinical risk profiles to the quality of anticoagulation control in the warfarin
      arm. Primary efficacy (composite of stroke, systemic embolic event, myocardial
      infarction, and cardiovascular death) and safety (composite of major and
      clinically relevant nonmajor bleeding) outcomes and time to therapeutic range
      (TtTR) and time in therapeutic range (TiTR) were analyzed in relation to CHA2DS2
      VASc (congestive heart failure, hypertension, age >=75 years (2 points), diabetes
      mellitus, stroke (2 points), vascular disease, age 65-74 years, sex category) and
      HAS-BLED (hypertension, age, stroke, bleeding tendency/predisposition, labile
      INRs, elderly age/frailty, drugs such as concomitant aspirin/nonsteroidal anti
      inflammatory drugs or alcohol excess) scores. A total of 1,095 patients were
      randomized to edoxaban and 1,104 received enoxaparin-warfarin. Mean age was 64.3
      +/- 10 and 64.2 +/- 11 years, respectively. Mean CHA2DS2-VASc score was 2.6
      (standard deviation [SD] 1.5 and 1.4, respectively) and mean HAS-BLED score was
      0.9 (SD 0.8) in both arms. There were nonsignificant trends toward lower odds
      ratios (ORs) for the efficacy end point in patients with CHA2DS2-VASc scores >2
      and higher ORs with HAS-BLED score >=3. Mean TiTR was >67%, with no differences
      between stroke or bleeding risk strata. The correlation between CHA2DS2-VASc and
      TtTR (p = 0.0286) and HAS-BLED and TiTR (p = 0.0286) were statistically
      significant. In patients who were at high risk of stroke, edoxaban had
      numerically lower primary efficacy end-point events and showed a trend for higher
      ORs, with HAS-BLED scores >=3 compared with enoxaparin-warfarin. TtTR was shorter
      with higher CHA2DS2-VASc scores, whereas bleeding risk was inversely correlated
      with quality of anticoagulation control.

PMID- 29169606
TI  - Presentation of the series "Cirrhosis of the liver and its complications".

PMID- 29169607
TI  - TC Rectal Pathology: Findings at CT-Colonography.
AB  - OBJECTIVE: To review the spectrum of benign and malignant rectal diseases, their
      findings on CT colonography, and their management. CONCLUSION: Although CT
      colonography is not the first choice for the study of rectal disease, it is
      indicated in cases where optical colonoscopy is contraindicated or cannot be
      completed. Rectal lesions can go undetected because this anatomic area is
      difficult to evaluate; for this reason, it is essential to ensure optimal
      preparation and distension, moderate balloon insufflation, and careful 2D and 3D
      navigation with knowledge of the spectrum of rectal disease and its CT
      colonography signs.

PMID- 29169608
TI  - Group 4: Replacement therapy for adrenal insufficiency.

PMID- 29169610
TI  - Out-of-pocket health expenditure differences in Chile: Insurance performance or
      selection?
AB  - Chile has a mixed health system with public and private actors engaged in
      provision and insurance. This dual system generates important differences in
      health expenditure between private and public insurances. Selection is a
      preeminent feature of the Chilean insurance system. In order to explain the role
      of the insurance in out-of-pocket expenditures between households for different
      insurance schemes, decomposition methods are applied to disentangle the effect of
      household 'composition and insurance' degree of financial protection on health
      expenditures. Health expenditure patterns have not changed in the last 10 years
      with drugs, outpatient care, and dental health representing 60% of the health
      expenditure. Health expenditure/income is similar for different income groups in
      the public insurance, but decreases with income in households with private
      coverage, reflecting regressivity in health expenditure. On the other hand,
      health expenditure as share of expenditure increases with income for both groups.
      Per capita health expenditure in households with private coverage is four times
      the expenditure of households with public insurance; this gap is mostly explained
      by differences in households' expenditure and demographics. Roughly 80% of the
      difference in expenditure is explained by the model, showing the role of
      selection in understanding the expenditure gap between insurance schemes.

PMID- 29169611
TI  - The Conduct and Reporting of Child Health Research: An Analysis of Randomized
      Controlled Trials Published in 2012 and Evaluation of Change over 5 Years.
AB  - OBJECTIVES: For child health randomized controlled trials (RCTs) published in
      2012, we aimed to describe design and reporting characteristics and evaluate
      changes since 2007; assess the association between trial design and registration
      and risk of bias (RoB); and assess the association between RoB and effect size.
      STUDY DESIGN: For 300 RCTs, we extracted design and reporting characteristics and
      assessed RoB. We assessed 5-year changes in design and reporting (based on 300
      RCTs we had previously analyzed) using the Fisher exact test. We tested for
      associations between design and reporting characteristics and overall RoB and
      registration using the Fisher exact, Cochran-Armitage, Kruskal-Wallis, and
      Jonckheere-Terpstra tests. We pooled effect sizes and tested for differences by
      RoB using the chi2 test for subgroups in meta-analysis. RESULTS: The 2012 and
      2007 RCTs differed with respect to many design and reporting characteristics.
      From 2007 to 2012, RoB did not change for random sequence generation and improved
      for allocation concealment (P < .001). Fewer 2012 RCTs were rated high overall
      RoB and more were rated unclear (P = .03). Only 7.3% of 2012 RCTs were rated low
      overall RoB. Trial registration doubled from 2007 to 2012 (23% to 46%) (P < .001)
      and was associated with lower RoB (P = .009). Effect size did not differ by RoB
      (P = .43) CONCLUSIONS: Random sequence generation and allocation concealment were
      not often reported, and selective reporting was prevalent. Measures to increase
      trialists' awareness and application of existing reporting guidance, and the
      prospective registration of RCTs is needed to improve the trustworthiness of
      findings from this field.

PMID- 29169609
TI  - Microglia-Mediated Neuroprotection, TREM2, and Alzheimer's Disease: Evidence From
      Optical Imaging.
AB  - Recent genetic studies have provided overwhelming evidence of the involvement of
      microglia-related molecular networks in the pathophysiology of Alzheimer's
      disease (AD). However, the precise mechanisms by which microglia alter the course
      of AD neuropathology remain poorly understood. Here we discuss current evidence
      of the neuroprotective functions of microglia with a focus on optical imaging
      studies that have revealed a role of these cells in the encapsulation of amyloid
      deposits ("microglia barrier"). This barrier modulates the degree of plaque
      compaction, amyloid fibril surface area, and insulation from adjacent axons
      thereby reducing neurotoxicity. We discuss findings implicating genetic variants
      of the microglia receptor, triggering receptor expressed on myeloid cells 2, in
      the increased risk of late onset AD. We provide evidence that increased AD risk
      may be at least partly mediated by deficient microglia polarization toward
      amyloid deposits, resulting in ineffective plaque encapsulation and reduced
      plaque compaction, which is associated with worsened axonal pathology. Finally,
      we propose possible avenues for therapeutic targeting of plaque-associated
      microglia with the goal of enhancing the microglia barrier and potentially
      reducing disease progression.

PMID- 29169612
TI  - Hepatic vein management in a parenchyma-sparing policy for resecting colorectal
      liver metastases at the caval confluence.
AB  - BACKGROUND: Patients with tumors involving hepatic vein at the caval-confluence
      usually receive major hepatectomies or hepatic vein grafting; however,
      nonnegligible postoperative mortality and morbidity are associated. Authors
      introduced the tumor-vessel detachment for colorectal liver metastases. Then we
      reviewed our results applying this approach in patients with colorectal liver
      metastases in contact with hepatic veins at the caval-confluence. METHODS: A
      cohort of consecutive patients with colorectal liver metastases in contact with
      hepatic veins at the caval-confluence undergoing liver surgery was reviewed.
      Relationships were classified as: Type 1: contact/involvement less than a third
      of hepatic vein circumference; Type 2: contact/involvement in a third to two
      thirds; Type 3: contact/involvement in more than two-thirds. Hepatic vein-
      colorectal liver metastases detachment, or in case of hepatic vein-resection, the
      sparing of the drained parenchyma, were attempted systematically. RESULTS:
      Overall 190 colorectal liver metastases-hepatic vein contacts in 135 patients
      were analyzed. Colorectal liver metastases-hepatic vein detachment was performed
      in 95 (50%) contacts, partial resection and direct suture in 61 (32%), partial
      resection and patching in 4 (2%), and hepatic vein complete resection in 30
      (16%). Hepatic vein-sparing resection was possible in 102 patients (76%), and
      major hepatectomy was needed in 1 (0.7%). Operative mortality, overall and major
      morbidity rate were 0.7%, 32%, and 4%, respectively. Local recurrence rate was 6%
      (median follow-up: 27 months). Preoperative and intraoperative imaging predicted
      the need for hepatic vein resection in 99% of patients (kappa = 0.971).
      CONCLUSIONS: Hepatic vein-sparing or a parenchyma-sparing policy is feasible in
      most patients with colorectal liver metastases-hepatic vein contacts at the caval
      confluence. This approach seems safe, predictable, and oncologically adequate,
      and, upon further confirmation, could become an alternative to major
      hepatectomies or hepatic vein replacement.

PMID- 29169613
TI  - Rectal neuroendocrine tumor as an incidental finding in the doughnut of rectal
      adenocarcinoma resection specimen. What would have happened if we had not
      examined the doughnut?

PMID- 29169614
TI  - Human papillomavirus viral load as a useful triage tool for non-16/18 high-risk
      human papillomavirus positive women: A prospective screening cohort study.
AB  - OBJECTIVE: ASCCP cervical cancer screening guidelines recommend triaging high
      risk human papillomavirus (hrHPV) positive women with cytology and genotyping,
      but cytology is often unavailable in resource-limited areas. We compared the long
      term risk of cervical cancer and precancers among type-specific hrHPV-positive
      women triaged by viral load to cytology and visual inspection with acetic acid
      (VIA). METHODS: A cohort of 1742 Chinese women was screened with cytology, VIA,
      and Hybrid Capture 2 (HC2) test and followed for ten years. All HC2-positive
      samples were genotyped. Viral load was measured by HC2 relative light
      units/cutoff (RLU/CO). Ten-year cumulative incidence rate (CIR) of cervical
      intraepithelial neoplasia grade 2 or worse (CIN2+) for type-specific hrHPV viral
      load was estimated using Kaplan-Meier methods. RESULTS: Baseline hrHPV viral load
      stratified by specific genotypes was positively correlated with prevalent
      cytological lesions. Ten-year CIR of CIN2+ was associated with cytological
      lesions and viral load. Among HPV 16/18-positive women, ten-year CIR of CIN2+ was
      high, even with normal cytology (15.3%), normal VIA (32.4%), viral load with
      RLU/CO<10 (23.6%) or RLU/CO<100 (33.8%). Among non-16/18 hrHPV positive women,
      ten-year CIR of CIN2+ was significantly stratified by cytology grade of atypical
      squamous cell of undetermined significance or higher (2.0% VS. 34.6%), viral load
      cutoffs at 10 RLU/CO (5.1% VS. 27.2%), at 100 RLU/CO (11.0% VS. 35.5%), but not
      by VIA (19.1% VS. 19.0%). CONCLUSIONS: Our findings support the guidelines in
      referring all HPV16/18 positive women to colposcopy and suggest triaging non
      16/18 hrHPV positive women using viral loads in resource-limited areas where
      cytology screening was inaccessible.

PMID- 29169615
TI  - Morbidity and reversal rate of ileostomy after bowel resection during Visceral
      Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer.
AB  - OBJECTIVE: To investigate the morbidity of diverting loop ileostomy (DLI)
      performed during Visceral Peritoneal Debulking (VPD) for stage IIIC-IV ovarian
      cancer and to report the rate, timing, and morbidity of DLI reversal. METHODS: We
      retrieved the data of all consecutive patients who underwent sigmoid-rectum
      resection (SRR) followed by DLI. Morbidity was defined as any surgical/medical
      complications clearly correlated to the DLI. The reversal rate of DLI was defined
      as the number of patients who had the continuity of the gastrointestinal tract
      restored in the study period. Finally, we recorded the timing and the morbidity
      of the reversal surgery. Factors associated with non-reversal of DLI were
      reported. RESULTS: In the study period (01/2010-09/2016), complete data were
      available for 47 patients. Stoma-related complications occurred in 22 patients
      (46.8%). Eight patients (17.0%) were readmitted within 30days from surgery.
      Thirty-two patients (68.1%) had their stoma reversed. The primary cause of non
      reversal was tumor recurrence/progression (7/15, 46.7%). Patient's age, length of
      hospitalization, complications after VPD were associated with non-reversal of
      DLI. The mean time from DLI formation to stoma reversal was 6months (+/-1.7).
      Post-reversal related complications occurred in 37.1% of the patients.
      CONCLUSIONS: In our series, 31.9% of the patients with FIGO stage IIIC-IV ovarian
      cancer who underwent SRR and DLI did not have stoma reversal. Overall they had
      approximately 45% risk of stoma-related morbidity and 37% risk of morbidity
      related to the stoma reversal. This information should be part of the consulting
      process when preparing for debulking surgery, particularly in patients who are
      likely to need a bowel resection.

PMID- 29169616
TI  - Characterizing Microscopical Invasion Patterns in Canine Mast Cell Tumours and
      Soft Tissue Sarcomas.
AB  - Stromal invasion is identified commonly in cutaneous malignancies; however,
      invasive patterns are defined inconsistently and their clinical relevance is
      uncertain. This study aimed to define objective, quantifiable histomorphological
      invasive patterns in low-grade canine mast cell tumours (MCTs) and grade I/II
      soft tissue sarcomas (STSs), and correlate invasive patterns with overall
      excisional status. Haematoxylin and eosin-stained glass slides prepared for
      routine histopathology of surgically-excised tumours from client-owned dogs were
      evaluated for invasion beyond their subgross edge, asymmetrical invasion,
      satellite lesions, lymphovascular invasion, perineurovascular growth, growth
      along fascial planes, intramuscular invasion and multicompartmental involvement.
      Digital histological tumour-free margins <1 mm in any direction were considered
      to represent an incomplete excision. Fifty-one dogs with 69 tumours (50 MCTs and
      19 STSs) were included in the study. Invasion in both circumferential and deep
      directions was significantly greater in MCTs compared with STSs (exact 2-tailed P
      <0.0001 circumferential; P = 0.0095 deep). Within the MCT group, circumferential
      invasion was greater than deep invasion (P = 0.0076). Multivariate logistic
      regression analysis found two variables that were significantly associated with
      incomplete MCT excision: intraoperative grossly normal circumferential surgical
      margin size (odds ratio of 0.776, 95% confidence interval: 0.651-0.925) and
      asymmetry invasion index (odds ratio of 1.318, 95% confidence interval: 1.039
      1.671). These data may help create evidence-based strategies for planning
      surgical resections of cutaneous malignancies. Presence of asymmetrical
      microscopical invasion might prompt pathologists to perform more comprehensive
      surgical margin evaluation.

PMID- 29169617
TI  - Primary Histiocytic Sarcoma of the Brain in an African Hedgehog (Atelerix
      albiventris).
AB  - A 2.5-year-old African hedgehog (Atelerix albiventris) with signs of progressive
      paresis/paralysis for approximately 6 months was diagnosed with 'wobbly hedgehog
      syndrome' (WHS). Post-mortem examination revealed a primary central nervous
      system (CNS) histiocytic sarcoma (HS) associated with neurodegenerative changes
      of the CNS and skeletal muscle atrophy. Grossly, a spherical mass infiltrated the
      left forebrain and was located between the frontal lobe and thalamus in coronal
      sections. Microscopically, the neoplastic cells had eccentrically located
      anisokaryotic nuclei and abundant eosinophilic cytoplasm. Immunohistochemically,
      they were positive for calcium-binding adapter molecule 1, lysozyme, CD68 and
      vimentin. Ultrastructurally, the neoplastic cells had varying amounts of bundles
      and whorls of intermediate filaments and scattered lysosomes. This report
      represents the first documentation of primary CNS HS in this species. Primary CNS
      HS should be considered as a differential diagnoses for hedgehogs that present
      with neurological signs of WHS.

PMID- 29169618
TI  - Clinical Pathology of the Vulnerable Gough Moorhen (Gallinula comeri).
AB  - The Gough moorhen (Gallinula comeri) is native to Gough Island, Tristan da Cunha,
      and listed as Vulnerable by the International Union for Conservation of Nature
      due to its restricted range and susceptibility to introduced predators. A planned
      ecosystem restoration by eradication of introduced house mice (Mus musculus) via
      aerially delivered rodenticide requires a reproductively balanced population of
      Gough moorhens to be held in captivity to avoid primary and secondary poisoning.
      To aid disease detection during the period of captivity, Gough moorhens (n = 43;
      25 adult females and 18 adult males) were captured, measured and sampled to
      determine ease of sexing by morphometrics, to establish reference ranges for
      routine haematological and biochemical parameters and to identify any intestinal
      and haemoparasites as well as determine which faecal bacteria were present. Male
      Gough moorhens had significantly greater mean body mass (P = 0.019) and head and
      bill length (P = 0.001) compared with females, but the overlapping ranges showed
      genetic identification of sex was required for accurate determination. Plasma
      globulin and total protein concentrations were significantly greater in female
      compared with male birds (P = 0.032 and P = 0.012, respectively) and probably
      related to egg yolk production. No haemoparasites or gastrointestinal parasites
      were found in any bird and there were no sex-related differences in the
      haematology. Multiple bacterial taxa were isolated from the faeces of all birds
      including Enterococcus spp. (n = 42), Klebsiella spp. (n = 40), Staphylococcus
      aureus (n = 33), Staphylococcus intermedius (n = 16), Escherichia coli (n = 41)
      and Pseudomonas spp. (n = 7). No clinical or subclinical disease was found in any
      of the birds examined, suggesting they are suitable for short-term captivity but
      rapid on-island genetic-based sex determination will be essential to ensure a
      reproductively balanced population.

PMID- 29169619
TI  - Immunohistochemical Validation of Spontaneously Arising Canine Osteosarcoma as a
      Model for Human Osteosarcoma.
AB  - Osteosarcoma (OS) originates from bone-forming mesenchymal cells and represents
      one of the primary bone tumours. It is the most common primary bone tumour in
      dogs and man. The characterization of an appropriate natural disease animal model
      to study human OS is essential to elucidate the pathogenesis of the disease. This
      study aimed to validate canine OS as a model for the human disease by evaluating
      immunohistochemically the expression of markers known to be important in human
      OS. The immunohistochemical panel included vimentin, alkaline phosphatase (ALP),
      desmin, S100, neuron-specific enolase (NSE), runt-related transcription factor 2
      (Runx2) and bone morphogenetic protein 4 (BMP4). Immunohistochemistry was
      conducted on formalin-fixed, paraffin wax-embedded tissue sections from 59 dogs
      with confirmed primary OS. Vimentin, ALP, Runx2 and BMP4 were highly expressed by
      all tumours, while desmin, S100 and NSE were expressed variably. The findings
      were similar to those described previously for human OS and suggest that canine
      OS may represent a useful model for the study of the human disease.

PMID- 29169620
TI  - Pancreatic Colloid Carcinoma in an Elderly Cat.
AB  - A 21-year-old neutered female domestic shorthaired cat was presented with a
      history of inappetence, vomiting and haematuria. The cat was humanely destroyed
      at the owner's request and a necropsy examination was performed. A 0.8 * 0.5 *
      0.5 cm mass was located in the left lobe of the pancreas. The mass was gelatinous
      in nature and the external and cut surfaces were pale yellow in colour.
      Microscopically, the mass was non-capsulated and comprised an accumulation of
      extracellular stromal mucin containing suspended neoplastic columnar epithelial
      cells forming tubular structures. Immunohistochemically, these cells diffusely
      expressed cytokeratin (CK) AE1/AE3, CK7 and carcinoembryonic antigen and were
      partially positive for CK19 and trypsin, but negative for vimentin. The tumour
      was diagnosed as a colloid carcinoma. The clinical presentation in this case was
      caused by chronic renal failure complicated by secondary renal
      hyperparathyroidism and associated metastatic calcinosis. To the best of our
      knowledge, this is the first report of colloid carcinoma arising from the
      pancreas in a cat.

PMID- 29169622
TI  - Cardiac Truncus Arteriosus in an Eastern Black Rhinoceros (Diceros bicornis
      michaeli).
AB  - This case report describes congenital truncus arteriosus in a 1-month-old Eastern
      black rhinoceros (Diceros bicornis michaeli). From the first day of life the
      animal was underweight and from the 22nd day of life displayed respiratory signs
      that exacerbated with time leading eventually to collapse and death. Post-mortem
      examination revealed a single truncus arteriosus originating from the right
      ventricle leading to two separated pulmonary arteries and the aorta, with the
      ventricular septum showing a focal communicating defect. Based on the gross
      examination and current human classifications, the truncus arteriosus was
      classified as type III or A2. This is the first description of persistent truncus
      arteriosus in an Eastern black rhinoceros.

PMID- 29169621
TI  - 120 years of Louping-ill Research: an Historical Perspective from the Archive of
      the Journal of Comparative Pathology.

PMID- 29169623
TI  - Endocardial Peripheral Nerve Sheath Tumour with Features of a Benign Schwannoma
      in a Donkey.
AB  - A peripheral nerve sheath tumour, with features of a benign schwannoma and
      arising from the endocardium of the right ventricle, was found incidentally
      during routine post-mortem examination of a 28-year-old gelding donkey.
      Macroscopically, five round to oval, white to grey and red, firm masses, firmly
      attached to the endocardium were identified. Microscopically, the endocardium and
      adjacent subendocardium were infiltrated by a variably demarcated, non
      encapsulated mesenchymal neoplasm with features of a benign schwannoma, including
      concurrent presence of Antoni A and Antoni B areas, nuclear palisading,
      neoplastic cells with enlarged bizarre nuclei ('ancient change') and the
      formation of Verocay-like bodies. Immunohistochemically, the tumour cells were
      variably strongly positive for expression of S100 and glial fibrillary acidic
      protein. This is the first cardiac tumour reported in a donkey and is
      macroscopically, histologically and immunohistochemically similar to endocardial
      schwannoma occurring in Wistar rats.

PMID- 29169624
TI  - Suspected Hepadnavirus Association with a Hepatocellular Carcinoma in a Black
      Tailed Prairie Dog (Cynomys ludovicianus).
AB  - Hepatocellular carcinomas are the most commonly reported neoplasm of black-tailed
      prairie dogs (Cynomys ludovicianus). In several other closely related Sciuridae
      species, infection with species-specific hepadnaviruses is associated with the
      development of these tumours, but such a hepadnavirus has not yet been identified
      in any prairie dog species, although its presence has been hypothesized
      previously. An adult prairie dog was humanely destroyed due to progressive
      illness and the identification of a cranial abdominal mass that was determined on
      histopathology to be a hepatocellular carcinoma. Deep sequencing of the tumour
      tissue identified the presence of a hepadnavirus, similar in its genetic
      structure to woodchuck hepatitis virus. Electron microscopy showed the presence
      of viral particles similar in structure to other hepadnaviral particles. This
      report suggests that a hepadnavirus may be associated with the development of
      hepatocellular carcinomas in the prairie dog.

PMID- 29169625
TI  - Ovarian Embryonal Carcinoma in a Dog.
AB  - A 17-month-old female doberman pinscher was referred for an abdominal mass and
      ascites. Exploratory laparotomy revealed the presence of a large neoplastic mass
      replacing the right ovary and associated with multiple mesovarian, mesometrial
      and peritoneal nodules. An ovariohysterectomy was performed. Grossly, the tumour
      was soft and multilocular with large areas of haemorrhage and necrosis.
      Microscopically, it was infiltrative and composed of round and polygonal cells
      arranged respectively in solid sheets or forming distorted tubular structures
      separated by thick fibrovascular septae. Tubules contained necrotic debris,
      proteinaceous fluid or small endoluminal papillary structures. Marked cellular
      atypia, multiple neoplastic emboli and high mitotic count were observed.
      Immunohistochemically, the round cells uniformly expressed placental alkaline
      phosphatase, while the polygonal cells arranged in tubules and papillae expressed
      cytokeratin (CK) AE1/AE3 and CK7. A final diagnosis of metastasizing ovarian
      embryonal carcinoma (EC), a primitive germ cell tumour characterized by
      rudimentary epithelial differentiation was made. Canine ovarian EC should be
      considered as a differential diagnosis for undifferentiated aggressive ovarian
      tumours in young dogs.

PMID- 29169626
TI  - Intra-oral Sebaceous Gland Tumours in Two Dogs.
AB  - A 12-year-old female miniature schnauzer and a 12-year-old neutered female cocker
      spaniel each had a grey-yellow nodular lesion arising from the gingiva.
      Microscopical examination showed that both nodules were composed of varied
      proportions of sebocytes and basal-type reserve cells with few ducts lined by
      stratified squamous epithelium. Based on the histopathological findings, the
      cases were diagnosed as sebaceous adenoma and sebaceous epithelioma,
      respectively. In man, the occurrence of sebaceous neoplasms in the oral cavity
      has been reported to some extent, but these lesions are very rare in animals. To
      the best of our knowledge, this is the first report of intra-oral sebaceous
      neoplasms in dogs. Intra-oral sebaceous epithelioma has never been reported in
      animals.

PMID- 29169627
TI  - Cytomegalic Inclusion Disease caused by Cytomegalovirus Infection in the Salivary
      Glands of an African Hedgehog (Atelerix arbiventris).
AB  - Cytomegalic inclusion disease (CID) in the salivary gland of African hedgehogs
      (Atelerix arbiventris) has been reported before, and is suspected to reflect a
      cytomegalovirus infection. However, a recent ultrastructural study reported that
      African hedgehog CID reflected oncocytic metaplasia, mimicking a cytomegalovirus
      infection. We examined the submandibular and sublingual salivary glands of a 1
      year-old male African hedgehog. Histologically, there were multiple foci composed
      of cytomegalic cells with intranuclear inclusion bodies. Ultrastructurally, viral
      particles (109-118 nm in diameter) were observed in the nuclei of the cytomegalic
      cells. There were numerous vesicles containing various numbers of enveloped
      viruses in the cytoplasm. We also attempted to detect viral DNA fragments by
      degenerate polymerase chain reaction and obtained amplicons of a predicted size.
      Phylogenetic analysis indicated that the virus is a betaherpesvirus,
      comparatively related to human and rodent cytomegaloviruses. The present study
      suggested that African hedgehog CIDs also include those caused by the
      cytomegalovirus.

PMID- 29169628
TI  - Spinal Cord Compression in a Horse due to a Granular Cell Variant of
      Neurofibroma.
AB  - A neurofibroma of granular cell subtype is described in a 7-year-old horse. The
      horse had a 3-month history of ataxia affecting the forelimbs and hindlimbs,
      suggesting a C1-C6 neuroanatomical localization. Post-mortem examination revealed
      an intradural mass arising from the right sixth cervical spinal nerve and
      compressing the spinal cord. Histologically, the mass was composed largely of
      wavy spindle cells (a mixture of Schwann cells, perineurial cells and
      fibroblasts) intimately associated with ropy collagen fibres. Approximately 25%
      of the spindle cells were swollen and contained densely-packed, eosinophilic and
      periodic acid-Schiff-positive cytoplasmic granules. Immunohistochemistry for S100
      and glial fibrillary acidic protein antigens labelled a proportion of neoplastic
      cells, while the cytoplasmic granules were positive for S100 and neuron specific
      enolase. This is the first report of a neurofibroma with granular cell
      differentiation in an animal. Granular cell differentiation in other peripheral
      nerve sheath tumours of animals is briefly discussed.

PMID- 29169629
TI  - Suppurative Inflammation and Local Tissue Destruction Reduce the Penetration of
      Cefuroxime to Infected Bone Implant Cavities.
AB  - Treatment of post-traumatic and implant-associated osteomyelitis (IAO) includes
      surgical debridement, removal of implants and long-term antibiotic therapy. The
      success of antibiotic therapy relies not only on activity towards the infecting
      pathogen, but also on sufficient penetration of the target site. The aim of the
      present study was to characterize the local pathological changes associated with
      reduced penetration of cefuroxime to infected bone implant cavities. Previously,
      reduced penetration of systemically administrated cefuroxime was demonstrated in
      the implant cavity of 10 pigs with Staphylococcus aureus IAO present for 5 days.
      In the present study, a comprehensive histopathological characterization of the
      peri-implant bone tissue was performed and correlated with the reduced
      penetration of cefuroxime. In two pigs, the levels of oxygen, pyruvate and
      lactate was estimated in the implant cavity. A peri-implant pathological bone
      area (PIBA) developed with a width of 1.2 up to 3.8 mm. PIBAs included: (1)
      suppuration, resulting in destruction of the implant cavity contour, and (2) a
      non-vascular zone of primarily necrotic bone tissue. A strong negative
      correlation was seen between PIBA width and cefuroxime area under the
      concentration time curves (AUC[0-last]) and peak concentration of cefuroxime
      (Cmax). All metabolic measurements demonstrated hypoxia. In conclusion, subacute
      suppurative bone inflammation with local tissue destruction can result in
      decreased penetration of antibiotics and insufficient oxygen supply.

PMID- 29169630
TI  - Kinetic analysis of canine gait on the effect of failure tendon repair and tendon
      graft.
AB  - Kinetic analysis of canine gait has been extensively studied, including normal
      and abnormal gait. However, no research has looked into how flexor tendon injury
      and further treatment would affect the walking pattern comparing to the uninjured
      state. Therefore, this study was aimed to utilize a portable pressure walkway
      system, which has been commonly used for pedobarographic and kinetic analysis in
      the veterinary field, to examine the effect of a failed tendon repair and tendon
      graft reconstruction on canine digit kinetics during gait. 12 mixed breed
      (mongrel) hound-type female dogs were included in this study and 2nd and 5th
      digits were chosen to undergo flexor tendon repair and graft surgeries. Kinetic
      parameters from the surgery leg in stance phase were calculated. From the
      results, after tendon failure repair, decrease of weight bearing was seen in the
      affected digits and weight bearing was shifted to the metacarpal pad. After
      tendon graft reconstruction, weight bearing returned to the affected digits and
      metacarpal pads. Slight alteration in peak pressure and instant of peak force
      were identified, but it was estimated to have little influence on post
      reconstruction gait. This study could serve as a reference in evaluating canine
      digit function in flexor tendon injury for future studies.

PMID- 29169631
TI  - Functional MRI can detect changes in intratissue strains in a full thickness and
      critical sized ovine cartilage defect model.
AB  - Functional imaging of tissue biomechanics can reveal subtle changes in local
      softening and stiffening associated with disease or repair, but noninvasive and
      nondestructive methods to acquire intratissue measures in well-defined animal
      models are largely lacking. We utilized displacement encoded MRI to measure
      changes in cartilage deformation following creation of a critical-sized defect in
      the medial femoral condyle of ovine (sheep) knees, a common in situ and large
      animal model of tissue damage and repair. We prioritized visualization of local,
      site-specific variation and changes in displacements and strains following defect
      placement by measuring spatial maps of intratissue deformation. Custom data
      smoothing algorithms were developed to minimize propagation of noise in the
      acquired MRI phase data toward calculated displacement or strain, and to improve
      strain measures in high aspect ratio tissue regions. Strain magnitudes in the
      femoral, but not tibial, cartilage dramatically increased in load-bearing and
      contact regions especially near the defect locations, with an average 6.7% +/-
      6.3%, 13.4% +/- 10.0%, and 10.0% +/- 4.9% increase in first and second principal
      strains, and shear strain, respectively. Strain heterogeneity reflected the
      complexity of the in situ mechanical environment within the joint, with multiple
      tissue contacts defining the deformation behavior. This study demonstrates the
      utility of displacement encoded MRI to detect increased deformation patterns and
      strain following disruption to the cartilage structure in a clinically-relevant,
      large animal defect model. It also defines imaging biomarkers based on
      biomechanical measures, in particular shear strain, that are potentially most
      sensitive to evaluate damage and repair, and that may additionally translate to
      humans in future studies.

PMID- 29169632
TI  - Effects of annular contraction on anterior leaflet strain using an in vitro
      simulator with a dynamically contracting mitral annulus.
AB  - Using in vitro models, the mechanics as well as surgical techniques for mitral
      valves (MV) and MV devices can be studied in a more controlled environment with
      minimal monetary investment and risk. However, these current models rely on
      certain simplifications, one being that the MV has a static, rigid annulus. In
      order to study more complex issues of imaging diagnostics and implanted device
      function, it would be more advantageous to verify their use for a dynamic
      environment in a dynamic simulator. This study provides the novel design and
      development of a dynamically contracting annulus (DCA) within an in vitro
      simulator, and its subsequent use to study MV biomechanics. Experiments were
      performed to study the ability of the DCA to reproduce the MV leaflet mechanics
      in vitro, as seen in vivo, as well as investigate how rigid annuloplasties affect
      MV leaflet mechanics. Experiments used healthy, excised MVs and normal
      hemodynamics; contractile waveforms were derived from human in vivo data.
      Stereophotogrammetry and echocardiography were used to measure anterior leaflet
      strain and the change in MV geometry. In pursuit of the first in vitro MV
      simulator that more completely represents the dynamic motion of the full valvular
      apparatus, this study demonstrated the successful operation of a dynamically
      contracting mitral annulus. It was seen that the diseased contractile state
      increased anterior leaflet strain compared to the healthy contractile state. In
      addition, it was also shown in vitro that simulated rigid annuloplasty increased
      mitral anterior leaflet strain compared to a healthy contraction.

PMID- 29169633
TI  - Pathology and genetics of hereditary colorectal cancer.
AB  - Colorectal cancer (CRC) accounts for over 8% of all deaths annually worldwide.
      Between 2 and 5% of all CRCs occur due to inherited syndromes, including Lynch
      syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, Peutz
      Jeghers syndrome, juvenile polyposis and Cowden/PTEN hamartoma syndrome. In
      addition, serrated polyposis is a clinically defined condition characterised by
      multiple colorectal serrated polyps and an increased risk of CRC but the genetics
      are not known. In most hereditary CRC syndromes, polyps undergo carcinogenesis,
      but the exact route to carcinoma seems to differ between the conditions.
      Discovery of the key germline mutations in these syndromes has been instrumental
      to our understanding of the underlying molecular mechanisms of colorectal
      carcinogenesis. This review summarises the genetic and pathological alterations
      in hereditary CRC syndromes.

PMID- 29169635
TI  - Environmental triggers in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect
      almost any organ in the human body. Despite significant advancements in our
      understanding of SLE over the recent years, its exact mode of onset and disease
      progression remains elusive. Low concordance rates among monozygotic twins with
      SLE (as low as 24%), clustering of disease prevalence around polluted regions and
      an urban-rural difference in prevalence all highlight the importance of
      environmental influences in SLE. Experimental data strongly suggests a complex
      interaction between the exposome (or environmental influences) and genome
      (genetic material) to produce epigenetic changes (epigenome) that can alter the
      expression of genetic material and lead to development of disease in the
      susceptible individual. In this review, we focus on the available literature to
      explore the role of environmental factors in SLE disease onset and progression
      and to better understand the role of exposome-epigenome-genome interactions in
      this dreaded disease.

PMID- 29169636
TI  - Sub-retinal lens fragment in optical coherence tomography after complicated
      cataract surgery.

PMID- 29169637
TI  - Engraving of Pulbius Horatius Cocles ("the one-eyed man") by Georg Pencz.

PMID- 29169634
TI  - The Emerging Neurobiology of Bipolar Disorder.
AB  - Bipolar disorder (BD) is a leading cause of global disability. Its biological
      basis is unknown, and its treatment unsatisfactory. Here, we review two recent
      areas of progress. First, the discovery of risk genes and their implications,
      with a focus on voltage-gated calcium channels as part of the disease process and
      as a drug target. Second, facilitated by new technologies, it is increasingly
      apparent that the bipolar phenotype is more complex and nuanced than simply one
      of recurring manic and depressive episodes. One such feature is persistent mood
      instability, and efforts are underway to understand its mechanisms and its
      therapeutic potential. BD illustrates how psychiatry is being transformed by
      contemporary neuroscience, genomics, and digital approaches.

PMID- 29169638
TI  - Epidermoid carcinoma of the conjunctiva associated with human papillomavirus.

PMID- 29169639
TI  - Posterior scleritis follow-up by Swept-Source optical coherence tomography.

PMID- 29169640
TI  - The ocular loss of the radio inventor, Guglielmo Marconi.

PMID- 29169641
TI  - Treatment of pulmonary and extrapulmonary tuberculosis.
AB  - The purpose of tuberculosis treatment is twofold: to provide an individual
      benefit centred on healing the patient with TB, and to provide a collective
      benefit to the community in which the patient resides. The different treatment
      regimens for tuberculosis sensitive to first-line antituberculosis drugs as well
      as resistant tuberculosis are examined and the peculiarities in the management of
      pulmonary and extrapulmonary tuberculosis are discussed.

PMID- 29169642
TI  - [Lens dislocation into the anterior chamber].

PMID- 29169643
TI  - Solvent Front Position Extraction procedure with thin-layer chromatography as a
      mode of multicomponent sample preparation for quantitative analysis by
      instrumental technique.
AB  - A concept of using thin-layer chromatography to multicomponent sample preparation
      for quantitative determination of solutes followed by instrumental technique is
      presented. Thin-layer chromatography (TLC) is used to separate chosen substances
      and their internal standard from other components (matrix) and to form a single
      spot/zone containing them at the solvent front position. The location of the
      analytes and internal standard in the solvent front zone allows their easy
      extraction followed by quantitation by HPLC.

PMID- 29169644
TI  - Liquid chromatography coupled to tandem mass spectrometry for detecting ten
      allergens in complex and incurred foodstuffs.
AB  - Food allergy is a considerable heath problem, as undesirable contaminations by
      allergens during food production are still widespread and may be dangerous for
      human health. To protect the population, laboratories need to develop reliable
      analytical methods in order to detect allergens in various food products.
      Currently, a large majority of allergen-related food recalls concern bakery
      products. It is therefore essential to detect allergens in unprocessed and
      processed foodstuffs. In this study, we developed a method for detecting ten
      allergens in complex (chocolate, ice cream) and processed (cookie, sauce)
      foodstuffs, based on ultra-high performance liquid chromatography coupled to
      tandem mass spectrometry (UHPLC-MS/MS). Using a single protocol and considering a
      signal-to-noise ratio higher than 10 for the most abundant multiple reaction
      monitoring (MRM) transition, we were able to detect target allergens at 0.5mg/kg
      for milk proteins, 2.5mg/kg for peanut, hazelnut, pistachio, and cashew proteins,
      3mg/kg for egg proteins, and 5mg/kg for soy, almond, walnut, and pecan proteins.
      The ability of the method to detect 10 allergens with a single protocol in
      complex and incurred food products makes it an attractive alternative to the
      ELISA method for routine laboratories.

PMID- 29169645
TI  - Application of enzymatic probe sonication for selenium speciation in animal
      feeds.
AB  - Enzymatic probe sonication (EPS) was investigated as a novel and alternative
      technology for the extraction of five Se species SeCys2, MeSeCys, Se (IV), SeMet
      and Se (VI) from animal feeds. The critical parameters of EPS such as enzyme
      types, ultrasonic power, sample/enzyme ratio, extraction time and temperature
      were carefully optimized. Under current conditions, one sample can be extracted
      in 60s, in contrast to several hours required by the conventional enzymatic
      methods Moreover, the extraction is performed in pure water, no further
      temperature control or pH adjustment is needed, and therefore the risk of species
      interconvertion is drastically reduced or inhibited. The Se species were
      separated and quantitatively determined by high-performance liquid chromatography
      hydride generation atomic fluorescence spectrometry (HPLC-HG-AFS), which allows
      the separation of organic and inorganic Se species in a single chromatographic
      run. The newly developed method was successfully applied to the determination of
      Se species in 18 feed samples collected from markets and local farms. Concerning
      the feed samples studied, the results of this work suggest that stricter measures
      should be taken to control the Se-enriched feed supplements in terms of Se
      species.

PMID- 29169646
TI  - Development of an intelligent surgical training system for Thoracentesis.
AB  - Surgical training improves patient care, helps to reduce surgical risks,
      increases surgeon's confidence, and thus enhances overall patient safety. Current
      surgical training systems are more focused on developing technical skills, e.g.
      dexterity, of the surgeons while lacking the aspects of context-awareness and
      intra-operative real-time guidance. Context-aware intelligent training systems
      interpret the current surgical situation and help surgeons to train on surgical
      tasks. As a prototypical scenario, we chose Thoracentesis procedure in this work.
      We designed the context-aware software framework using the surgical process model
      encompassing ontology and production rules, based on the procedure descriptions
      obtained through textbooks and interviews, and ontology-based and marker-based
      object recognition, where the system tracked and recognised surgical instruments
      and materials in surgeon's hands and recognised surgical instruments on the
      surgical stand. The ontology was validated using annotated surgical videos, where
      the system identified "Anaesthesia" and "Aspiration" phase with 100% relative
      frequency and "Penetration" phase with 65% relative frequency. The system tracked
      surgical swab and 50mL syringe with approximately 88.23% and 100% accuracy in
      surgeon's hands and recognised surgical instruments with approximately 90%
      accuracy on the surgical stand. Surgical workflow training with the proposed
      system showed equivalent results as the traditional mentor-based training regime,
      thus this work is a step forward a new tool for context awareness and decision
      making during surgical training.

PMID- 29169647
TI  - An EEG-based functional connectivity measure for automatic detection of alcohol
      use disorder.
AB  - BACKGROUND: The abnormal alcohol consumption could cause toxicity and could alter
      the human brain's structure and function, termed as alcohol used disorder (AUD).
      Unfortunately, the conventional screening methods for AUD patients are subjective
      and manual. Hence, to perform automatic screening of AUD patients, objective
      methods are needed. The electroencephalographic (EEG) data have been utilized to
      study the differences of brain signals between alcoholics and healthy controls
      that could further developed as an automatic screening tool for alcoholics.
      METHOD: In this work, resting-state EEG-derived features were utilized as input
      data to the proposed feature selection and classification method. The aim was to
      perform automatic classification of AUD patients and healthy controls. The
      validation of the proposed method involved real-EEG data acquired from 30 AUD
      patients and 30 age-matched healthy controls. The resting-state EEG-derived
      features such as synchronization likelihood (SL) were computed involving 19 scalp
      locations resulted into 513 features. Furthermore, the features were rank-ordered
      to select the most discriminant features involving a rank-based feature selection
      method according to a criterion, i.e., receiver operating characteristics (ROC).
      Consequently, a reduced set of most discriminant features was identified and
      utilized further during classification of AUD patients and healthy controls. In
      this study, three different classification models such as Support Vector Machine
      (SVM), Naive Bayesian (NB), and Logistic Regression (LR) were used. RESULTS: The
      study resulted into SVM classification accuracy=98%, sensitivity=99.9%,
      specificity=95%, and f-measure=0.97; LR classification accuracy=91.7%,
      sensitivity=86.66%, specificity=96.6%, and f-measure=0.90; NB classification
      accuracy=93.6%, sensitivity=100%, specificity=87.9%, and f-measure=0.95.
      CONCLUSION: The SL features could be utilized as objective markers to screen the
      AUD patients and healthy controls.

PMID- 29169648
TI  - [Cancer stem cells: The true revolution, at last?]

PMID- 29169649
TI  - [Cancer stem cells: Definition and isolation techniques].

PMID- 29169650
TI  - [Use of alternative donors for allogeneic haematopoietic cell transplantation in
      lymphoid neoplasms: Guidelines from the Francophone Society of Bone Marrow
      Transplantation and Cellular Therapy (SFGM-TC)].
AB  - Despite great improvements in the outcome of patients with lymphoma, some may
      still relapse or present with primary refractory disease. In these situations,
      allogeneic haematopoietic cell transplantation (allo-HCT) is a potentially
      curative option, in particular in the case of relapse after autologous stem cell
      transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have
      started to challenge the use of allo-HCT for relapsed or refractory lymphoma.
      During the 2016 annual workshop of the Francophone Society of Bone Marrow
      Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive
      review of the literature published in the last 10 years and established
      guidelines to clarify the indications and transplant modalities in this setting.
      This manuscript reports on general considerations regarding allo-HCT for lymphoma
      and elaborates on the use of alternative donors in this setting.

PMID- 29169651
TI  - [Preservation/congelation of hematopoietic stem cell grafts in a pediatric
      context: Guidelines from the Francophone Society of Bone Marrow Transplantation
      and Cellular Therapy (SFGM-TC)].
AB  - The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM
      TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical
      practices harmonization workshop series in September 2016 in Lille, France. The
      objective of our workshop is to provide a discussion on the conservation and
      congelation of hematopoietic stem cells in a pediatric setting as well as our
      recommendations for this technique.

PMID- 29169652
TI  - [The experience of a biotechnology company for preclinical studies of drugs
      targeting cancer stem cells].

PMID- 29169653
TI  - [How to manage EBV reactivation and EBV-PTLD, CMV and human herpesvirus 6
      reactivation and infection after allogeneic stem cell transplantation: A report
      of the SFGM-TC (update)].
AB  - The French society of bone marrow transplantation and cell therapy (SFGM-TC)
      organizes annually workshops in the attempt to harmonize clinical practices
      between different francophone transplantation center. Here, we report our
      recommendations regarding the management of Epstein Barr virus reactivation and
      lymphoproliferative disorders, cytomegalovirus (CMV) and human herpes virus 6
      (HHV6) after allogeneic stem cell transplantation.

PMID- 29169654
TI  - [The concept of cancer stem cell].

PMID- 29169655
TI  - [Cancer stem cells and precision medicine].

PMID- 29169656
TI  - Cardiovascular responses to intranasal neuropeptide Y in single prolonged stress
      rodent model of post-traumatic stress disorder.
AB  - Delivery of neuropeptide Y (NPY) to the brain by intranasal administration shows
      promise as non-invasive means for preventing or treating PTSD symptoms. Here,
      radiotelemetry and echocardiography were used to determine effects of intranasal
      NPY on cardiovascular functions in absence and presence of stress. Male adult
      Sprague Dawley rats were implanted with radiotelemetric probes, and subjected to
      single prolonged stress (SPS), followed by intranasal vehicle (V) or NPY (150MUg)
      under conditions shown to prevent development of many of the behavioral
      neuroendocrine and biochemical impairments. In both groups, mean arterial
      pressure (MAP) rose rapidly peaking at about 125mmHg, remaining near maximal
      levels for 1h. SPS also elicited robust rise in heart rate (HR) which was
      mitigated by intranasal NPY, and significantly lower than V-treated rats 12-50min
      after exposure to SPS stressors. In the first hr. after SPS, locomotor activity
      was elevated but only in the V-treated group. By 3h, MAP returned to pre-stress
      levels in both groups with no further change when monitored for 6days. HR
      remained elevated during the 6h remaining light phase after SPS. Subsequently HR
      was at pre-SPS levels during the remaining days. However dark phase HR was low
      following SPS, gradually recovered over 6days and was associated with reduced
      activity. When administered in the absence of further stress, intranasal NPY or V
      elicited similar much smaller, short-lived rises in MAP and HR. Echocardiography
      revealed no change in HR, stroke volume (SV) or cardiac output (Q) with
      intranasal NPY in the absence of stress. SPS led to reduced SV and Q but was not
      affected by NPY. Overall the results demonstrate no major cardiovascular effects
      of intranasal NPY and indicate possible benefit from transient amelioration of HR
      response in line with its translational potential to combat PTSD and comorbid
      impairments.

PMID- 29169657
TI  - Short interactive workshops reduce variability in contouring treatment volumes
      for spine stereotactic body radiation therapy: Experience with the ESTRO FALCON
      programme and EduCaseTM training tool.
AB  - We report the results of 4, 2-h contouring workshops on target volume definition
      for spinal stereotactic radiotherapy. They combined traditional teaching methods
      with a web-based contouring/contour-analysis platform and led to a significant
      reduction in delineation variability. Short, interactive workshops can reduce
      interobserver variability in spine SBRT target volume delineation.

PMID- 29169658
TI  - [Symmetrical peripheral gangrene: 4 cases].
AB  - BACKGROUND: Symmetric peripheral gangrene (SPG) is a symmetrical distal ischemic
      lesion on at least 2 or more extremities in the absence of proximal arterial
      obstruction and vasculitis. It is a rare and severe clinical entity. The aim of
      this study was to describe clinical symptoms, etiological agents and the
      management of SPG through a series of 4 cases. PATIENTS AND METHODS: We included
      all cases of SPG hospitalized between 2000 and 2014. The inclusion criterion was
      the presence of distal ischemic damage at two or more sites in the absence of
      large vessel obstruction. RESULTS: Four patients (2 men and 2 women) were
      included. The mean age was 43.2+/-12 years. Two patients had a history of
      splenectomy. All patients had blackening of the tips of the fingers and toes.
      Three patients presented with septic shock. The etiology was bacteremia involving
      Streptococcus pneumoniae in two cases and a malignant form of Mediterranean
      spotted fever (MSF). In addition to specific antibiotics, we used a potent
      vasodilator (iloprost) in two cases and curative heparin therapy in two cases.
      The outcome was favorable in 3 cases, with regression of necrotic lesions. One
      case required the amputation of non-perfused necrotic fingers and toes.
      CONCLUSION: SPG can complicate MSF in some rare cases. Thorough and repeated skin
      examinations are essential to ensure timely diagnosis and treatment of GPS in
      order to improve the prognosis.

PMID- 29169659
TI  - Acquisition of the mcr-1 gene by a high-risk clone of KPC-2-producing Klebsiella
      pneumoniae ST437/CC258, Brazil.
AB  - We identified one clinical isolate of K. pneumoniae harboring the mcr 1 (plasmid
      of IncX4 family) and blaKPC-2 (plasmid of IncFIB family) genes in southern
      Brazil. These findings highlight that K. pneumoniae isolates carrying both mcr-1
      and blaKPC-2 may emergence as a serious threat to antimicrobial therapy.

PMID- 29169660
TI  - Reward and loss anticipation in panic disorder: An fMRI study.
AB  - Anticipatory anxiety and harm avoidance are essential features of panic disorder
      (PD) and may involve deficits in the reward system of the brain, in particular in
      the ventral striatum. While neuroimaging studies on PD have focused on fearful
      and negative affective stimulus processing, no investigations have directly
      addressed deficits in reward and loss anticipation. To determine whether the
      ventral striatum shows abnormal neural activity in PD patients during
      anticipation of loss or gain, an event-related functional magnetic resonance
      imaging experiment using a monetary incentive delay task was employed in 10
      patients with PD and 10 healthy controls. A repeated-measures ANOVA to identify
      effects of group (PD vs. Control) and condition (anticipation of loss vs. gain
      vs. neutral outcome) revealed that patients with PD showed significantly reduced
      bilateral ventral striatal activation during reward anticipation but increased
      activity during loss anticipation. Within the patient group, the degree of
      activation in the ventral striatum during loss-anticipation was positively
      correlated with harm avoidance and negatively correlated with novelty seeking.
      These findings suggest that behavioural impairments in panic disorder may be
      related to abnormal neural processing of motivational cues.

PMID- 29169661
TI  - Light irradiance through novel CAD-CAM block materials and degree of conversion
      of composite cements.
AB  - OBJECTIVE: To assess light irradiance (LI) delivered by two light-curing units
      (LCU's) and to measure the degree of conversion (DC) of three composite cements,
      when cured through different thicknesses of two novel CAD-CAM block materials.
      METHODS: 100-MUm-thick films of a dual-curable composite cement (G-CEM LinkAce,
      GC), a light-curable flowable resin-based composite (RBC) (G-aenial Universal
      Flo, GC) and a micro-hybrid RBC (G-aenial Posterior, GC) were investigated as
      luting agents. Two 'polymer-ceramic' CAD-CAM blocks (Cerasmart, GC; Enamic, Vita
      Zahnfabrik) were sectioned in slabs with different thicknesses (1, 3 and 5mm). LI
      at the bottom of the specimens was measured using a calibrated spectrometer,
      while being light-cured through the CAD-CAM block slabs for 40s with a low- (+/
      500mW/cm2) or high- (+/-1,600mW/cm2) irradiance LCU (n=5). After light-curing,
      micro-Raman spectra of the composite films were acquired to determine DC at 5min,
      10min, 1h and 24h. LI data were statistically analyzed by Kruskal-Wallis followed
      by post-hoc comparisons, while a linear mixed-effect model was applied for the DC
      analysis. In addition, the CAD-CAM blocks ultrastructure was characterized upon
      argon-ion slicing using scanning transmission electron microscopy (STEM).
      Finally, light transmission (LT) through each CAD-CAM block material was assessed
      using a spectrophotometer. RESULTS: Curing-light attenuation and DC were
      significantly influenced by thickness and type of the overlying material. LCU
      only had a significant effect on DC of the micro-hybrid RBC. DC significantly
      increased over time for all composite cements. CAD-CAM block structural analysis
      revealed a relatively small and homogenous filler configuration (mean filler size
      of 0.2-0.5MUm) for Cerasmart, while Enamic contained ceramic grains varying in
      shape and size (1-10MUm), which were interconnected by the polymer-based network.
      LT was much higher at a wavelength range of 300-800nm for Cerasmart than for
      Enamic. SIGNIFICANCE: Light-curable composite cements can be cured through a
      restoration up to 2.7-mm thickness, depending on the kind of CAD-CAM material. A
      high-irradiance LCU only has a limited effect on the maximum thickness of the
      polymer-ceramic CAD-CAM material that can be cured through.

PMID- 29169662
TI  - Effects of Contrast Enhancement on In-Body Calibrated Phantomless Bone Mineral
      Density Measurements in Computed Tomography.
AB  - We aimed to test the potential of phantomless volumetric bone mineral density
      (PLvBMD) measurements for the determination of volumetric bone mineral density
      (vBMD) in routine contrast-enhanced computed tomography (CECT). We evaluated 56
      tri-phasic abdominal computed tomography scans, including an unenhanced scan as
      well as defined CECT scans in the arterial and portalvenous phase. PLvBMD
      analysis was performed by 4 radiologists using an FDA-approved tool for
      phantomless evaluation of bone density (IntelliSpace, Philips, The Netherlands).
      Mean vBMD of the first 3 lumbar vertebrae in each contrast phase was determined
      and interobserver variance of vBMD independent of contrast phase was analyzed
      using intraclass correlation, Bland-Altman plots, and Student's t test. CECT
      scans were associated with a significantly higher PLvBMD compared with unenhanced
      scans (unenhanced computed tomography: 97.8 mg/cc; arterial CECT: 106.3 mg/cc,
      portalvenous CECT: 106.3 mg/cc). Overall, there was no significant difference of
      PLvBMD between data acquisition in arterial and portalvenous phases (increase of
      8.6% each, standard deviation ratio 37.7%-38.3%). In Bland-Altman analysis, there
      was no evidence of a relevant reader-related bias or an increase in standard
      deviation of PLvBMD measurements in contrast-enhanced scans compared with
      unenhanced scans. The following conversion formulas for unenhanced PLvBMD were
      determined: unenhancedPLvBMD=0.89*arterialPLvBMD+3,74mg/cc(r2 = 0.94) and
      unenhancedPLvBMD=0.88*venousPLvBMD+4,56mg/cc(r2 = 0.93). Compared with the
      results of phantom-based quantitative computed tomography measurements reported
      in the literature, the PLvBMD changes associated with contrast enhancement were
      relatively moderate with an increase of 8.6% in average. The time-point of the
      contrast-enhanced PLvBMD measurements after injection of contrast media did not
      appear to affect the results. With the adjustment formulas provided in this
      study, the method can improve osteoporosis screening through detection of reduced
      bone mass of the vertebrae in routinely conducted CECT.

PMID- 29169663
TI  - Polysialylated Neural Cell Adhesion Molecule Supports Regeneration of Neurons in
      the Nucleus Ambiguus After Unilateral Recurrent Laryngeal Nerve Avulsion in Adult
      Rats.
AB  - OBJECTIVES: A correlation appears to exist between the expression of the
      polysialic acid neural cell adhesion molecule (PSA-NCAM) and repair in central
      nervous system (CNS) diseases. However, the expression of PSA-NCAM in the CNS
      after peripheral nerve injury remains unclear. This study aimed to evaluate the
      expression of PSA-NCAM in the ipsilateral nucleus ambiguus (NA) after unilateral
      recurrent laryngeal nerve (RLN) avulsion. MATERIALS AND METHODS: The left RLN of
      adult Sprague Dawley rats were avulsed. The expression of PSA-NCAM, PSA
      NCAM/NeuN, and PSA-NCAM/Tuj1 in the brain stem was investigated using
      immunohistochemistry. The results were subjected to one-way analysis of variance
      followed by the Tukey post hoc test for statistical analyses. RESULTS: PSA-NCAM
      positive and PSA-NCAM/NeuN and PSA-NCAM/Tuj1 double-labeled positive cells were
      observed 7 days post injury in the ipsilateral NA. PSA-NCAM/NeuN and PSA
      NCAM/Tuj1 double-labeled cells were observed at 21 and 7 days post injury,
      respectively. PSA-NCAM/NeuN double-labeled cells were also found in the
      contralateral NA. CONCLUSIONS: After unilateral avulsion of the RLN, the
      expression of PSA-NCAM in the ipsilateral NA was correlated with the
      proliferation and the differentiation of neural cells. PSA-NCAM expression may be
      used as a predictor of the initiation of repair in neural cells.

PMID- 29169665
TI  - Mindfulness and craving: effects and mechanisms.
AB  - Mindfulness meditation has a long tradition of being used to manage cravings.
      This paper reviews 30 experimental studies that have examined the effects of
      different types of mindfulness practice on cravings for food, cigarettes and
      alcohol. The findings are interpreted in light of relevant theories of craving.
      The studies show most support for the elaborated intrusion theory of desire and
      conditioning models. They suggest that whilst mindfulness strategies may bring
      about immediate reductions in craving, such effects are likely to stem from
      working memory load, and will not necessarily be superior to alternative
      strategies that also load working memory. Likewise, reductions in craving over
      the medium term may occur due to extinction processes that result from the
      individual inhibiting craving-related responses. Again, alternative strategies
      that promote response suppression may be equally effective. Nevertheless, a
      smaller number of studies show promising results where mindfulness exercises have
      been repeatedly practiced over a longer period of time. The results of these
      studies provide tentative support for Buddhist models of craving that suggest
      mindfulness practice may confer unique benefits in terms of both craving
      reduction and reducing the extent to which craving leads to consumption. Further
      research would be needed to confirm this.

PMID- 29169664
TI  - Long-term efficacy of psychotherapy for posttraumatic stress disorder: A meta
      analysis of randomized controlled trials.
AB  - Psychotherapies are well established as efficacious acute interventions for
      posttraumatic stress disorder (PTSD). However, the long-term efficacy of such
      interventions and the maintenance of gains following termination is less
      understood. This meta-analysis evaluated enduring effects of psychotherapy for
      PTSD in randomized controlled trials (RCTs) with long-term follow-ups (LTFUs) of
      at least six months duration. Analyses included 32 PTSD trials involving 72
      treatment conditions (N=2935). Effect sizes were significantly larger for active
      psychotherapy conditions relative to control conditions for the period from
      pretreatment to LTFU, but not posttreatment to LTFU. All active interventions
      demonstrated long-term efficacy. Pretreatment to LTFU effect sizes did not
      significantly differ among treatment types. Exposure-based treatments
      demonstrated stronger effects in the posttreatment to LTFU period (d=0.27)
      compared to other interventions (p=0.005). Among active conditions, LTFU effect
      sizes were not significantly linked to trauma type, population type, or intended
      duration of treatment, but were strongly tied to acute dropout as well as whether
      studies included all randomized patients in follow-up analyses. Findings provide
      encouraging implications regarding the long-term efficacy of interventions and
      the durability of symptom reduction, but must be interpreted in parallel with
      methodological considerations and study characteristics of RCTs.

PMID- 29169666
TI  - Erratum to "Postoperative Adjuvant and Salvage Radiotherapy for Prostate Cancer:
      Impact on Freedom From Biochemical Relapse and Survival".

PMID- 29169667
TI  - No benefit of arthroscopy in subacromial shoulder pain.

PMID- 29169669
TI  - Department of Error.

PMID- 29169670
TI  - Are patients satisfied with the head and neck skin cancer service? An evaluation
      of outpatient services with a review of published reports.
AB  - Scientific publications place much emphasis on postoperative outcomes such as
      recurrence, but little attention to patients' satisfaction. The purpose of this
      evaluation was to find out patients' reported outcomes after their initial
      consultation, treatment, and follow-up appointments for non-melanoma skin cancer
      of the head and neck. We used an adapted version of the European Organisation for
      Research and Treatment of Cancer (EORTC) validated questionnaire for patients'
      satisfaction to collect data prospectively from consenting patients between
      September and December 2015. A total of 179 questionnaires were completed
      (initial consultation n=51, treatment n=74, and follow up n=54). Patients were
      most satisfied with the appointments for treatment (Kruskal-Wallis p<0.001, mean
      (SD) score 4.86/5 (0.15)), and 87% regarding the service as excellent. Patients
      were least satisfied with services and organisation of care compared with nurses
      and doctors (Kruskal-Wallis p<0.001). There seemed to be most satisfaction after
      the appointment for treatment. A possible explanation could simply be the relief
      of having finally had their cancer removed. Patients are also likely to show
      greater satisfaction with the clinical team because of the personal nature of the
      interaction that they experience during this aspect of their care.

PMID- 29169668
TI  - Arthroscopic subacromial decompression for subacromial shoulder pain (CSAW): a
      multicentre, pragmatic, parallel group, placebo-controlled, three-group,
      randomised surgical trial.
AB  - BACKGROUND: Arthroscopic sub-acromial decompression (decompressing the sub
      acromial space by removing bone spurs and soft tissue arthroscopically) is a
      common surgery for subacromial shoulder pain, but its effectiveness is uncertain.
      We did a study to assess its effectiveness and to investigate the mechanism for
      surgical decompression. METHODS: We did a multicentre, randomised, pragmatic,
      parallel group, placebo-controlled, three-group trial at 32 hospitals in the UK
      with 51 surgeons. Participants were patients who had subacromial pain for at
      least 3 months with intact rotator cuff tendons, were eligible for arthroscopic
      surgery, and had previously completed a non-operative management programme that
      included exercise therapy and at least one steroid injection. Exclusion criteria
      included a full-thickness torn rotator cuff. We randomly assigned participants
      (1:1:1) to arthroscopic subacromial decompression, investigational arthroscopy
      only, or no treatment (attendance of one reassessment appointment with a
      specialist shoulder clinician 3 months after study entry, but no intervention).
      Arthroscopy only was a placebo as the essential surgical element (bone and soft
      tissue removal) was omitted. We did the randomisation with a computer-generated
      minimisation system. In the surgical intervention groups, patients were not told
      which type of surgery they were receiving (to ensure masking). Patients were
      followed up at 6 months and 1 year after randomisation; surgeons coordinated
      their waiting lists to schedule surgeries as close as possible to randomisation.
      The primary outcome was the Oxford Shoulder Score (0 [worst] to 48 [best]) at 6
      months, analysed by intention to treat. The sample size calculation was based
      upon a target difference of 4.5 points (SD 9.0). This trial has been registered
      at ClinicalTrials.gov, number NCT01623011. FINDINGS: Between Sept 14, 2012, and
      June 16, 2015, we randomly assigned 313 patients to treatment groups (106 to
      decompression surgery, 103 to arthroscopy only, and 104 to no treatment). 24
      [23%], 43 [42%], and 12 [12%] of the decompression, arthroscopy only, and no
      treatment groups, respectively, did not receive their assigned treatment by 6
      months. At 6 months, data for the Oxford Shoulder Score were available for 90
      patients assigned to decompression, 94 to arthroscopy, and 90 to no treatment.
      Mean Oxford Shoulder Score did not differ between the two surgical groups at 6
      months (decompression mean 32.7 points [SD 11.6] vs arthroscopy mean 34.2 points
      [9.2]; mean difference -1.3 points (95% CI -3.9 to 1.3, p=0.3141). Both surgical
      groups showed a small benefit over no treatment (mean 29.4 points [SD 11.9], mean
      difference vs decompression 2.8 points [95% CI 0.5-5.2], p=0.0186; mean
      difference vs arthroscopy 4.2 [1.8-6.6], p=0.0014) but these differences were not
      clinically important. There were six study-related complications that were all
      frozen shoulders (in two patients in each group). INTERPRETATION: Surgical groups
      had better outcomes for shoulder pain and function compared with no treatment but
      this difference was not clinically important. Additionally, surgical
      decompression appeared to offer no extra benefit over arthroscopy only. The
      difference between the surgical groups and no treatment might be the result of,
      for instance, a placebo effect or postoperative physiotherapy. The findings
      question the value of this operation for these indications, and this should be
      communicated to patients during the shared treatment decision-making process.
      FUNDING: Arthritis Research UK, the National Institute for Health Research
      Biomedical Research Centre, and the Royal College of Surgeons (England).

PMID- 29169671
TI  - Enhanced recovery in patients having free tissue transfer for head and neck
      cancer: does it make a difference?
AB  - Programmes for Enhanced Recovery after Surgery (ERAS) accelerate recovery, reduce
      morbidity, and shorten hospital stay in a wide range of surgical specialties. We
      established a standardised multimodal ERAS pathway for patients who were being
      treated by free tissue transfer for head and neck cancer to evaluate its benefit.
      Our primary outcome was duration of hospital stay, and secondary outcomes
      included complications, number of days to first mobilisation, and readmission
      rates. We compared 100 consecutive patients who followed the ERAS programme with
      a control group of 40 consecutive patients who had free tissue transfer before
      the ERAS programme was introduced. There was a significantly reduced median
      duration of stay from 14days in the control group to 10days in the ERAS group.
      Patients in the ERAS group who were aged over 60 years, or had tracheostomies, or
      who required bone resection also had a significantly reduced duration of stay.
      There was no difference between morbidity and readmission rates, although
      patients in the ERAS group were mobilised significantly earlier. The ERAS
      programme is safe and effective for patients who are treated by free tissue
      transfer for head and neck cancer, and potentially reduces their duration of stay
      in hospital.

PMID- 29169672
TI  - Corrigendum to "Novel images and novel locations of familiar images as sensitive
      translational cognitive tests in humans" [Behav. Brain Res. 285 (2015) 53-59].

PMID- 29169675
TI  - Developing a Multidisciplinary Vascular Anomalies Clinic and Reviewing the
      Radiologist's Clinic Role.
AB  - Cutaneous vascular anomalies can be challenging to diagnose and treat given their
      rare presentation and that they do not always fall under the purview of a
      specific medical specialty. Patients with cutaneous vascular anomalies are best
      managed in vascular anomalies clinics, but to our knowledge, no reported
      publications exist on how to develop such a clinic. In this article, we describe
      the specifics steps our institution took to create a vascular anomalies clinic
      and discuss how it benefitted our patients and referring providers. We also
      highlight the roles of the diagnostic and interventional radiologist within a
      vascular anomalies clinic.

PMID- 29169674
TI  - Identification of a 4-fluorobenzyl l-valinate amide benzoxaborole (AN11736) as a
      potential development candidate for the treatment of Animal African
      Trypanosomiasis (AAT).
AB  - Novel l-valinate amide benzoxaboroles and analogues were designed and synthesized
      for a structure-activity-relationship (SAR) investigation to optimize the growth
      inhibitory activity against Trypanosoma congolense (T. congolense) and
      Trypanosoma vivax (T. vivax) parasites. The study identified 4-fluorobenzyl (1
      hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-l-valinate (5,
      AN11736), which showed IC50 values of 0.15 nM against T. congolense and 1.3 nM
      against T. vivax, and demonstrated 100% efficacy with a single dose of 10 mg/kg
      against both T. congolense and T. vivax in mouse models of infection (IP dosing)
      and in the target animal, cattle, dosed intramuscularly. AN11736 has been
      advanced to early development studies.

PMID- 29169673
TI  - Design and synthesis of a biaryl series as inhibitors for the bromodomains of
      CBP/P300.
AB  - A novel, potent, and orally bioavailable inhibitor of the bromodomain of CBP,
      compound 35 (GNE-207), has been identified through SAR investigations focused on
      optimizing al bicyclic heteroarene to replace the aniline present in the
      published GNE-272 series. Compound 35 has excellent CBP potency (CBP IC50 = 1 nM,
      MYC EC50 = 18 nM), a selectively index of >2500-fold against BRD4(1), and
      exhibits a good pharmacokinetic profile.

PMID- 29169676
TI  - Gastrointestinal Stromal Tumor of the Jejunum With Active Bleeding Demonstrated
      on Dual-Energy MDCT Angiography: A Case Report.
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the
      gastrointestinal tract and may occasionally present with acute gastrointestinal
      bleed (GIB). Multidetector computed tomography (MDCT) angiography is extremely
      useful in demonstrating the tumor as well as the presence of active hemorrhage,
      thereby guiding subsequent interventional or surgical management. We report a
      case of a 38-year-old man who presented with acute-onset melena and compensated
      shock, whose source of bleed remained elusive on endoscopy. MDCT angiography
      performed on a dual-energy scanner showed a jejunal tumor with active
      intraluminal contrast extravasation. The tumor was subsequently resected and the
      patient did well on follow-up. This was one of the few instances when MDCT
      angiography demonstrated active bleeding in a GIST and the first such case
      demonstrated on a dual-energy scanner.

PMID- 29169677
TI  - [Unexpected adverse events of immunotherapies in non-small cell lung cancer:
      About 2 cases].
AB  - Programmed death receptor 1 (PD1) checkpoint inhibitors are known for immune
      mediated toxicities such as colitis, endocrinopathies and pneumonitis. However,
      other rare adverse effects are reported in the literature. Nivolumab is an anti
      PD1 immunotherapy used in the second line of non-small cell lung cancer (NSCLC).
      We report two cases of rare toxicities occurring under nivolumab in patients
      without a history of dysimmunity. A 79-year-old patient with a large-cell
      carcinoma showed a muscle weakness after the second course, revealing myositis
      with a CPK grade IV elevation as well as symptoms of myasthenia. The diagnosis of
      myositis was confirmed by a muscle biopsy. An 82-year-old patient followed for
      bronchial adenocarcinoma with EGFR mutation, presented with nivolumab shoulder
      and hip pain with extreme fatigue. After further investigations, the diagnosis of
      systemic erythematosus lupus was retained. Investigations led to the diagnosis of
      systemic lupus erythematosus. For both patients treatment was interrupted and
      systemic corticosteroid therapy was initiated permitting resolution of symptoms.
      The occurrence of symptoms of dysimmunity should attract the attention of the
      clinician, leading to discontinuation of anti-PD1 therapy and corticosteroid
      therapy. Retreatment after symptoms resolution must be collegially discussed if
      no alternative therapeutic is available.

PMID- 29169678
TI  - [Eight-year-old children with numerous food allergy inducer by passive exposition
      to cannabis].
AB  - We present a clinical case of a 8 old children with numerous food allergy inducer
      pas passive exposition to cannabis.

PMID- 29169679
TI  - Assessing the accuracy of body mass estimation equations from pelvic and femoral
      variables among modern British women of known mass.
AB  - Femoral head diameter is commonly used to estimate body mass from the skeleton.
      The three most frequently employed methods, designed by Ruff, Grine, and McHenry,
      were developed using different populations to address different research
      questions. They were not specifically designed for application to female remains,
      and their accuracy for this purpose has rarely been assessed or compared in
      living populations. This study analyzes the accuracy of these methods using a
      sample of modern British women through the use of pelvic CT scans (n = 97) and
      corresponding information about the individuals' known height and weight. Results
      showed that all methods provided reasonably accurate body mass estimates (average
      percent prediction errors under 20%) for the normal weight and overweight
      subsamples, but were inaccurate for the obese and underweight subsamples (average
      percent prediction errors over 20%). When women of all body mass categories were
      combined, the methods provided reasonable estimates (average percent prediction
      errors between 16 and 18%). The results demonstrate that different methods
      provide more accurate results within specific body mass index (BMI) ranges. The
      McHenry Equation provided the most accurate estimation for women of small body
      size, while the original Ruff Equation is most likely to be accurate if the
      individual was obese or severely obese. The refined Ruff Equation was the most
      accurate predictor of body mass on average for the entire sample, indicating that
      it should be utilized when there is no knowledge of the individual's body size or
      if the individual is assumed to be of a normal body size. The study also revealed
      a correlation between pubis length and body mass, and an equation for body mass
      estimation using pubis length was accurate in a dummy sample, suggesting that
      pubis length can also be used to acquire reliable body mass estimates. This has
      implications for how we interpret body mass in fossil hominins and has particular
      relevance to the interpretation of the long pubic ramus that is characteristic of
      Neandertals.

PMID- 29169680
TI  - Pounding tools in HWK EE and EF-HR (Olduvai Gorge, Tanzania): Percussive
      activities in the Oldowan-Acheulean transition.
AB  - In this paper, we present pounded objects from excavations at HWK EE and EF-HR,
      which are studied from macro and microscopic perspectives. Analysis of HWK EE
      revealed one of the largest collections of percussive objects from Olduvai Gorge,
      while excavations at EF-HR have allowed us to recover a much wider collection of
      percussive tools than previously recorded. Differences are observed between the
      two localities. At the Acheulean site of EF-HR, percussive tools were
      predominantly used in the production of flakes and large cutting tools (LCTs). At
      the Oldowan site of HWK EE, the tool repertoire probably related to a wider range
      of activities, including bone breaking and bipolar knapping. Comparison of these
      two assemblages, potentially produced by different hominin species, helps provide
      a wider picture of pounding activities during the Oldowan-Acheulean transition at
      Olduvai Gorge.

PMID- 29169681
TI  - Homo naledi pelvic remains from the Dinaledi Chamber, South Africa.
AB  - In the hominin fossil record, pelvic remains are sparse and are difficult to
      attribute taxonomically when they are not directly associated with craniodental
      material. Here we describe the pelvic remains from the Dinaledi Chamber in the
      Rising Star cave system, Cradle of Humankind, South Africa, which has produced
      hominin fossils of a new species, Homo naledi. Though this species has been
      attributed to Homo based on cranial and lower limb morphology, the morphology of
      some of the fragmentary pelvic remains recovered align more closely with
      specimens attributed to the species Australopithecus afarensis and
      Australopithecus africanus than they do with those of most (but not all) known
      species of the genus Homo. As with A. afarensis and A. africanus, H. naledi
      appears to have had marked lateral iliac flare and either a weakly developed or
      non-existent acetabulocristal buttress or a distinct, albeit weakly developed,
      acetabulospinous buttress. At the same time, H. naledi has robust superior pubic
      and ischiopubic rami and a short ischium with a narrow tuberoacetabular sulcus,
      similar to those found in modern humans. The fragmentary nature of the Dinaledi
      pelvic assemblage makes the attribution of sex and developmental age to
      individual specimens difficult, which in turn diminishes our ability to identify
      the number of individuals represented in the assemblage. At present, we can only
      confidently say that the pelvic fossils from Rising Star represent at least four
      individuals based on the presence of four overlapping right ischial fossils
      (whereas a minimum of 15 individuals can be identified from the Dinaledi dental
      assemblage). A primitive, early Australopithecus-like false pelvis combined with
      a derived Homo-like true pelvis is morphologically consistent with evidence from
      the lower ribcage and proximal femur of H. naledi. The overall similarity of H.
      naledi ilia to those of australopiths supports the inference, drawn from the
      observation of primitive pelvic morphology in the extinct species Homo
      floresiensis, that there is substantial variation in pelvic form within the genus
      Homo. In the light of these findings, we urge caution in making taxonomic
      attributions-even at the genus level-of isolated fossil ossa coxae.

PMID- 29169682
TI  - [Importance of hyponatraemia in older patients with hip fracture].

PMID- 29169683
TI  - Leukapheresis in 15 patients weighing 20kg or less: A single centre experience.
AB  - The application of apheresis equipment to perform leukapheresis (LK) in low
      weight paediatric patients is logistically complex and lacking of largest
      clinical performing experiences, meanwhile, the benefit from LK is controversial.
      In this study, 15 children with acute lymphoblastic leukemia(ALL)and acute
      myeloid leukemia (AML) and hyperleukocytosis were treated with the COBE Spectra
      apheresis system in the general paediatric ward by the staff from the department
      of Blood Transfusion. 26 LK procedures were performed. 12 patients (80%) were
      performed with peripheral veins, others (20%) with femoral veins. Median age,
      body weight of the patients was 4 years (range from1year 10 month to 7 years) and
      15kg (range from10 to 20kg). The median white blood cell (WBC) count of pre-first
      LK was 289*109/L (range from 108*109/L to 579*109/L). The median decrease in WBC
      count after each LK was 34% (range from 14% to 54%), and overall decrease in WBC
      after completion of LK procedures was 45% (range from 15% to 70%). All of the
      patients had no further signs of leukostasis and achieved marked reductions in
      WBC counts. Only minor clinical adverse events were attributable to LK. With
      adequate monitoring and experienced team, LK is a safe and may be a beneficial
      leukoreduction method in small patients weighing 20kg or less with ALL and AML.

PMID- 29169684
TI  - Airway morphology and inspiratory flow features in the early stages of Chronic
      Obstructive Pulmonary Disease.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is among the leading
      causes of death worldwide. Inhaled pollutants are the prime risk factor, but the
      pathogenesis and progression of the diseased is poorly understood. Most studies
      on the disease onset and trajectory have focused on genetic and molecular
      biomarkers. Here we investigate the role of the airway anatomy and the consequent
      respiratory fluid mechanics on the development of COPD. METHODS: We segmented CT
      scans from a five-year longitudinal study in three groups of smokers (18 subjects
      each) having: (i) minimal/mild obstruction at baseline with declining lung
      function at year five; (ii) minimal/mild obstruction at baseline with stable
      function, and (iii) normal and stable lung function over the five year period. We
      reconstructed the bronchial trees up to the 7th generation, and for one subject
      in each group we performed MRI velocimetry in 3D printed models. FINDINGS: The
      subjects with airflow obstruction at baseline have smaller airway diameters,
      smaller child-to-parent diameter ratios, larger length-to-diameter ratios, and
      smaller fractal dimensions. The differences are more significant for subjects
      that develop severe decline in pulmonary function. The secondary flows that
      characterize lateral dispersion along the airways are found to be less intense in
      the subjects with airflow obstruction. INTERPRETATION: These results indicate
      that morphology of the conducting airways and inspiratory flow features are
      correlated with the status and progression of COPD already at an early stage of
      the disease. This suggests that imaging-based biomarkers may allow a pre
      symptomatic diagnosis of disease progression.

PMID- 29169685
TI  - Surveillance of porcine reproductive and respiratory syndrome virus in the United
      States using risk mapping and species distribution modeling.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSv) outbreaks cause
      significant financial losses to the U.S. swine industry, where the pathogen is
      endemic. Seasonal increases in the number of outbreaks are typically observed
      using PRRSv epidemic curves. However, the nature and extent to which demographic
      and environmental factors influence the risk for PRRSv outbreaks in the country
      remains unclear. The objective of this study was to develop risk maps for PRRSv
      outbreaks across the United States (U.S.) and compare ecological dynamics of the
      disease in five of the most important swine production regions of the country.
      This study integrates spatial information regarding PRRSv surveillance with
      relevant demographic and environmental factors collected between 2009 and 2016.
      We used presence-only Maximum Entropy (Maxent), a species distribution modeling
      approach, to model the spatial risk of PRRSv in swine populations. Data fitted
      the selected model relatively well when the modeling approach was conducted by
      region (training and testing AUCs<0.75). All of the Maxent models selected
      identified high-risk areas, with probabilities greater than 0.5. The relative
      contribution of pig density to PRRSv risk was highest in pig-densely populated
      areas (Minnesota, Iowa and North Carolina), whereas climate and land cover were
      important in areas with relatively low pig densities (Illinois, Indiana, South
      Dakota, Nebraska, Kansas, Oklahoma, Colorado, and Texas). Although many previous
      studies associated the risk of PRRSv with high pig density and climatic factors,
      the study here quantifies, for the first time in the peer-reviewed literature,
      the spatial variation and relative contribution of these factors across different
      swine production regions in the U.S. The results will help in the design and
      implement of early detection, prevention, and control strategies for one of the
      most devastating diseases affecting the swine industry in the U.S.

PMID- 29169686
TI  - Diagnosing intramammary infection: Controlling misclassification bias in
      longitudinal udder health studies.
AB  - Using imperfect tests may lead to biased estimates of disease frequency and of
      associations between risk factors and disease. For instance in longitudinal udder
      health studies, both quarters at risk and incident intramammary infections (IMI)
      can be wrongly identified, resulting in selection and misclassification bias,
      respectively. Diagnostic accuracy can possibly be improved by using duplicate or
      triplicate samples for identifying quarters at risk and, subsequently, incident
      IMI. The objectives of this study were to evaluate the relative impact of
      selection and misclassification biases resulting from IMI misclassification on
      measures of disease frequency (incidence) and of association with hypothetical
      exposures. The effect of improving the sampling strategy by collecting duplicate
      or triplicate samples at first or second sampling was also assessed. Data sets
      from a hypothetical cohort study were simulated and analyzed based on a separate
      scenario for two common mastitis pathogens representing two distinct prevailing
      patterns. Staphylococcus aureus, a relatively uncommon pathogen with a low
      incidence, is identified with excellent sensitivity and almost perfect
      specificity. Coagulase negative staphylococci (CNS) are more prevalent, with a
      high incidence, and with milk bacteriological culture having fair Se but
      excellent Sp. The generated data sets for each scenario were emulating a
      longitudinal cohort study with two milk samples collected one month apart from
      each quarter of a random sample of 30 cows/herd, from 100 herds, with a herd
      level exposure having a known strength of association. Incidence of IMI and
      measure of association with exposure (odds ratio; OR) were estimated using Markov
      Chain Monte Carlo (MCMC) for each data set and using different sampling
      strategies (single, duplicate, triplicate samples with series or parallel
      interpretation) for identifying quarters at risk and incident IMI. For S. aureus
      biases were small with an observed incidence of 0.29 versus a true incidence of
      0.25IMI/100 quarter-month. In the CNS scenario, diagnostic errors in the two
      samples led to important selection (40IMI/100 quarter-month) and
      misclassification (23IMI/100 quarter-month) biases for estimation of IMI
      incidence, respectively. These biases were in opposite direction and therefore
      the incidence measure obtained using single sampling on both the first and second
      test (29IMI/100 quarter-month) was exactly the true value. In the S. aureus
      scenario the OR for association with exposure showed little bias (observed OR of
      3.1 versus true OR of 3.2). The CNS scenario revealed the presence of a large
      misclassification bias moving the association towards the null value (OR of 1.7
      versus true OR of 2.6). Little improvement could be brought using different
      sampling strategies aiming at improving Se and/or Sp on first and/or second
      sampling or using a two out of three interpretation for IMI definition.
      Increasing number of samples or tests can prevent bias in some situations but
      efforts can be spared by holding to a single sampling approach in others. When
      designing longitudinal studies, evaluating potential biases and best sampling
      strategy is as critical as the choice of test.

PMID- 29169687
TI  - Understanding the inhibitory mechanism of BIT225 drug against p7 viroporin using
      computational study.
AB  - P7 is the only viral channel encoded by the Hepatitis C Virus (HCV) genome. It is
      a small, highly hydrophobic protein containing 63 amino acids. Structural studies
      have shown that p7 has two transmembrane (TM) alpha helices linked by a short
      dibasic cytoplasmic loop. P7, mostly placed in the endoplasmic reticulum (ER), is
      a membrane-associated protein. The results obtained from different studies
      revealed that p7 is a polytopic membrane protein that could oligomerize in
      membrane bilayer to create ion channels with cation selectivity. In addition, p7
      is highly conserved and plays an important role in the assembly and release of
      mature viral particles. Thus, it can be considered as a potential target for anti
      HCV drugs. It has been found that several compounds (amantadine, rimantadine,
      hexamethylene amiloride (HMA) and long-alkyl-chain iminosugar (IS) derivatives)
      inhibit p7 channel ability. Another new inhibitor identified as BIT225, a
      derivative of amiloride, also inhibits the viroporin function of HIV-1 Vpu and
      HCV p7. In the present study, molecular dynamics simulations were applied to get
      insights into molecular details of a BIT225 binding site. In addition, the
      g_mmpbsa approach was employed to calculate the binding free energy and free
      energy decomposition per residue. MD simulation results in the p7-BIT225 complex
      revealed that drug binding to hydrophobic pocket can allosterically inhibit ion
      conduction via the funnel tip by restricting significant intrinsic channel breath
      at the tip of the funnel. Based on the molecular dynamics simulation (MD)
      analysis and the energy profiles, the hydrophobic interactions were the main
      driving force for BIT225 binding.

PMID- 29169688
TI  - Reply to "The insular cortex and QTc interval in HIV+ and HIV- individuals: Is
      there an effect of sympathetic nervous system activity?"

PMID- 29169689
TI  - Patient-Identified Barriers and Facilitators to Pre-Visit Patient-Reported
      Outcomes Measures Completion in Patients With Hip and Knee Pain.
AB  - BACKGROUND: Although patient-reported outcomes measures (PROMs) provide valuable
      health information and aid medical decision making for patients with hip and knee
      arthritis, survey completion rates remain low. The purpose of this study is to
      elucidate patient preferences regarding location of completion, delivery method,
      and barriers or facilitators to pre-visit completion. METHODS: Patients with hip
      and/or knee pain who were asked to complete pre-visit PROMs at 2 urban
      arthroplasty clinics were recruited. In-person, semi-structured, audio-recorded
      interviews were conducted, transcribed, and coded for thematic analysis. Codes
      were developed using a data-driven approach. RESULTS: We analyzed 51 interviews.
      The mean age was 57 years, 57% were women, and 45% had private or Medicare
      insurance. Prevalent themes regarding location preferences were convenience and
      communication preferences. Thirty-four patients stated a preference for
      completing pre-visit PROMs at home, 19 for in-office completion, and 10 stated no
      preference. Prevalent themes around delivery methods included technology access
      and familiarity. Of the 43 patients asked to select their preferred pre-visit
      PROM delivery method (phone call, email, text message, or postal mail), 31 (72%)
      preferred email or text messaging. Barriers to completing pre-visit PROMs were
      technological issues, recognizing the message was healthcare-related, and being
      too busy or forgetting. Twenty patients identified no barriers. CONCLUSION:
      Electronic PROM collection is favored by many patients, but alternative methods
      for patients without access to or familiarity with technology remain important.
      Clear recognition that the message is from a physician's office and physician
      communication of the utility of PROMs in clinical decision making may increase
      pre-visit completion.

PMID- 29169690
TI  - Evaluation of Surface Finish and Dimensional Control of Tribological Metal-Ultra
      High Molecular Weight Polyethylene Pair of Commercially Available Hip Implants.
AB  - BACKGROUND: Dimensional control and surface finish of the femoral head and
      acetabular liner are critical factors in the manufacturing process due to the
      risk of increased polyethylene wear, which is the primary cause of aseptic
      failure of a metal/polymer hip prosthesis. The aim of this study is to perform a
      dimensional and surface finish analysis to evaluate the reproduction and accuracy
      of the manufacturing processes of metal femoral heads and ultra high molecular
      weight polyethylene acetabular liners. METHODS: Four femoral heads and acetabular
      liners from 5 manufacturers were evaluated. The methods of evaluation followed
      the standards ISO 7206-2:2011 and ISO 21535:2010. RESULTS: The diameter,
      sphericity, and roughness of the femoral heads from all the manufacturers were in
      accordance with the standard requirements. Only the sphericity showed a lack of
      repeatability among the manufacturers. The variability in sphericity was high
      among some manufacturers and low in others. The diameters of the acetabular
      liners of 2 manufacturers were not in accordance with the standard requirements.
      The repeatability of sphericity, thickness, and roughness of the acetabular
      liners were heterogeneous among the manufacturers, which means that some
      manufacturers need to improve quality control. CONCLUSION: Our results showed a
      good dimensional and surface finish control of the manufacturing processes of the
      femoral heads. However, the same control was not shown during the manufacturing
      of the acetabular liners although all samples had a thickness and sphericity in
      accordance with the standard. A better quality control of the manufacturing
      process of ultra high molecular weight polyethylene acetabular liners should be
      made to improve the dimensional parameters of the acetabular liners and the
      tribological pair.

PMID- 29169691
TI  - Kocuria uropygioeca sp. nov. and Kocuria uropygialis sp. nov., isolated from the
      preen glands of Great Spotted Woodpeckers (Dendrocopos major).
AB  - Two new species of Gram-positive cocci were isolated from the uropygial glands of
      wild woodpeckers (Dendrocopos major) originating from different locations in
      Germany. A polyphasic approach confirmed the affiliation of the isolates to the
      genus Kocuria. Phylogenetic analysis based on the 16S rRNA gene showed high
      degree of similarity to Kocuria koreensis DSM 23367T (99.0% for both isolates).
      However, low ANIb values of <80% unequivocally separated the new species from K.
      koreensis. This finding was further corroborated by DNA fingerprinting and
      analysis of polar lipid profiles. Furthermore, growth characteristics,
      biochemical tests, MALDI-TOF MS analysis, and G+C contents clearly differentiated
      the isolates from their known relatives. Besides, the woodpecker isolates
      significantly differed from each other in their whole-cell protein profiles, DNA
      fingerprints, and ANIb values. In conclusion, the isolated microorganisms
      constitute members of two new species, for which the names Kocuria uropygioeca
      sp. nov. and Kocuria uropygialis sp. nov. are proposed. The type strains are 36T
      (DSM 101740T=LMG 29265T) and 257T (=DSM 101741T=LMG 29266T) for K. uropygialis
      sp. nov. and K. uropygioeca sp. nov., respectively.

PMID- 29169692
TI  - Anthropometric growth study of the ear in a Chinese population.
AB  - BACKGROUND: A large number of anthropometric studies of the auricle have been
      reported in different nations, but little data were available in the Chinese
      population. The aim of this study was to analyze growth changes in the ear by
      measuring the width and length of ears in a Chinese population. METHODS: A total
      of 480 participants were enrolled and classified into 1-, 3-, 5-, 7-, 9-, 12-, 14
      , and 18-year groups (half were boys and half were girls in each group). Ear
      length, ear width, body weight, and body length were measured and recorded; ear
      index was calculated according to ear length and ear width. The growth of auricle
      and differences between genders were analyzed. Growth of ear in relation to body
      height and weight and the degree of emphasis on the length and width of the
      auricle were also analyzed. RESULTS: Ear length and width increased with age. Ear
      length achieved its mature size in both 14-year-old males and females. Ear width
      reached its mature size in males at 7 years and in females at 5 years. Different
      trends of ear index were shown between males and females. People in this
      population paid more attention to the length than the width of the auricle.
      CONCLUSIONS: The data indicated that ear development followed increase in age.
      There were gender and ethnic difference in the development of ear. These results
      may have potential implications for the diagnosis of congenital malformations,
      syndromes, and planning of ear reconstruction surgery.

PMID- 29169693
TI  - Specific localization of manserin peptide in the rat carotid body.
AB  - The carotid body, located at the bifurcation of the common carotid artery, is a
      small sensory organ that detects changes in oxygen concentration and plays a
      vital role in controlling respiration. Although several molecules, such as
      neurotransmitters and neuropeptides, are involved in the regulation of the
      respiratory system, their detailed mechanisms have not been established yet. This
      study identifies that the presence of manserin, a neuropeptide, in the carotid
      body may play a crucial role in regulating respiration. The carotid bodies of
      adult Wistar rats were perfused with paraformaldehyde, and the frozen sections
      were subjected to immunohistochemical analyses. The carotid body comprises two
      distinct types of cells, neuron-like glomus cells and glial-like sustentacular
      cells. We used specific antibodies to distinguish the specific location of
      manserin in the carotid body, which included a tyrosine hydroxylase-positive
      antibody for glomus cells and an S100 protein antibody for sustentacular cells.
      Immunofluorescence analysis revealed that while tiny, round signals were
      exclusively observed in the cytoplasm of glomus cells, no signals were observed
      in sustentacular cells. Because manserin is believed to be secreted from
      precursor proteins by the endoproteolytic processing of a large precursor protein
      called secretogranin II, manserin secretion systems may exist in the carotid
      body, and thus, behave as potential regulators of respiration in the carotid
      body.

PMID- 29169694
TI  - Vitamin E can improve behavioral tests impairment, cell loss, and dendrite
      changes in rats' medial prefrontal cortex induced by acceptable daily dose of
      aspartame.
AB  - Aspartame is an artificial sweetener used in about 6000 sugar-free products.
      Aspartame consumption could be associated with various neurological disorders.
      This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex
      (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided
      into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day),
      and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day)
      respectively, with or without vitamin E consumption, for 8 weeks. Behavioral
      tests were recorded and the brain was prepared for stereological assessments.
      Novel objects test and eight-arm radial maze showed impairmentoflong- and short
      termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume,
      neurons number, glial cells number, dendrites length per neuron,and number of
      spines per dendrite length were decreased by 7-61% in the rats treated with
      aspartame. However, neurons' number, glial cells number, and rats' performance in
      eight-arm radial mazes were improved by concomitant consumption of vitamin E and
      aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the
      rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites
      length, spines number,and novel object recognition were not protected by
      treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of
      aspartame could induce memory impairments and cortical cells loss in mPFC.
      However, vitamin E could ameliorate some of these changes.

PMID- 29169695
TI  - Immunohistochemical analysis of the distribution of molecules involved in ionic
      and pH regulation in the lancelet Branchiostoma floridae (Hubbs, 1922).
AB  - The aim of present work is to analyse the distribution of carbonic anhydrase II
      (CAII), cystic fibrosis transmembrane regulator (CFTR), vacuolar-type H+-ATPase
      (V-H+-ATPase), Na+/K+ ATPase, Na+/H+ exchanger (NHE) and SLC26A6 (solute carrier
      family 26, member 6), also known as pendrin protein, in the lancelet
      Branchiostoma floridae in order to go in depth in the evolution of osmoregulation
      and pH regulation in Chordates. In view of their phylogenetic position, lancelets
      may indeed provide a critical point of reference for studies on osmoregulation
      evolution in Chordates. The results of present work demonstrated that, except to
      Na+/K+ ATPase that is strongly expressed in nephridia only, all the other studied
      molecules are abundantly present in skin, coelomic epithelium, renal papillae and
      nephridia and hepatic coecum. Thus, it is possible to hypothesize that also in
      lancelet, as in fish, these organs are involved in pH control and ionic
      regulation. In the digestive tract of B. floridae, the intestine epithelium was
      weakly immune-reactive to all tested antibodies, while the hepatic coecum showed
      an intense immunoreactivity to all molecules. Since in amphioxus the hepatic
      coecum functions simultaneously as stomach, liver and pancreas, these
      immunohistochemical results proved the secretion of H+ and HCO3- ions, typical of
      digestive process. Colocalization studies indicated a co-expression of the
      studied proteins in all considered organs, excluding NHE and pendrin for renal
      papillae, since some renal papillae are NHE immunopositive only.

PMID- 29169696
TI  - Efficacy and feasibility of opioids for burn analgesia: An evidence-based
      qualitative review of randomized controlled trials.
AB  - Opioids are commonly used for burn analgesia, but no comprehensive reviews have
      been published on such use. We aimed to assess the literature regarding the
      effectiveness and side effects of opioids both in adult and pediatric burn
      patients. We conducted a systematic search of the PubMed, Embase, Cochrane, and
      Web of Science databases. Information on study characteristics, results, and
      interventions was extracted. The review identified nine studies that satisfied
      the inclusion criteria. Burn sizes of patients ranged from 1% to 62% of the body.
      The examined studies showed that dressing or cream containing morphine could
      potentially decrease pain, use of analgesics, and side effects associated with
      systemic opioid medications compared with control groups. Oral transmucosal
      fentanyl citrate (OTFC) was equivalent, or even preferable, to oral morphine,
      hydromorphone, and oxycodone in provision of analgesia for burn wound care in
      pediatric patients. Intranasal fentanyl (INF) was equivalent to oral morphine in
      burn wound care both in adult and pediatric patients. OTFC and INF could be
      considered as viable non-invasive analgesic alternatives to oral opioids for
      procedural burn pain. However, the level of evidence still seems quite uncertain
      because of the limited sample size.

PMID- 29169697
TI  - Response to Letter to the Editor: 'Interactive home telemedicine and burns: A new
      method'.

PMID- 29169698
TI  - Avoiding overzealous excision of superficial burn and full excision of deep areas
      are two equally important prerequisites for successful early excision and
      grafting (EE&G).

PMID- 29169700
TI  - Interactive home telemedicine and burns: A new method.

PMID- 29169699
TI  - Burn clinical trials: A systematic review of registration and publications.
AB  - BACKGROUND: Randomized controlled clinical trials (CTs) are gold standard tools
      for assessing interventions. Although burn CTs have improved care, their status,
      publication frequency, and publication quality are not known. OBJECTIVES: (1)
      Characterize burn CTs by analyzing location, completion status, temporal trend,
      and funding sources. (2) Assess quality of trial reporting. DATA SOURCES: CT
      records were obtained from ClinicalTrials.gov and WHO's CT Registry (searched May
      2017). Publications were obtained from PubMed, Google Scholar, OVID MEDLINE, and
      ClinicalTrials.gov (searched June 2017). PUBLICATION APPRAISAL: 23-item rubric
      adapted from CONSORT and ICH E3 guidelines. RESULTS: 738 burn CTs were identified
      globally, of which majority were publically-funded (77%), ongoing (52%), and
      assessed behavioral, pharmacological, device-based, dietary-based, and
      biological/procedural interventions. Amongst the ended trials, 69 (28%) published
      their findings. Significantly fewer industry-funded trials published findings
      (14% vs 33% publically-funded). Quality of reporting was suboptimal, and most
      underreported categories were trial phase, severity, and sample size estimation.
      LIMITATIONS: Incomplete, outdated, and non-registered CTs which are difficult to
      track. CONCLUSIONS: Burn trials are proliferating in number, location, and
      interventions assessed. Only a small proportion are published and quality of
      reporting is suboptimal. IMPLICATIONS OF KEY FINDINGS: Burn researchers should
      aim to register and report on all clinical trials regardless of outcome. Superior
      a priori design can reduce precocious termination and mandatory reporting of data
      fields can improve quality of reporting. Systematic review registration number:
      CRD42017068549.

PMID- 29169701
TI  - Aromatherapy for the relief of symptoms in burn patients: A systematic review of
      randomized controlled trials.
AB  - BACKGROUND: Aromatherapy is often used to manage several conditions, including
      pain, psychological distress, and burn-related symptoms. The objective of this
      review was to assess the current evidence regarding the efficacy of aromatherapy
      as a treatment for burn wounds. METHODS: The following fifteen databases and
      trial registries were searched for studies published between their dates of
      inception and January 2017: AMED, CINAHL, EMBASE, MEDLINE, and the Cochrane
      Central Register of Controlled Trials (CENTRAL), as well as six Korean medical
      databases and four Iranian databases. All the trials included in the review were
      randomized controlled trials (RCTs) assessing the efficacy any type of
      aromatherapy as a treatment for burn-related symptoms. Study selection and data
      extraction were performed by two independent reviewers, and the risk of bias
      (ROB) in the trials included in the review was assessed using the Cochrane ROB
      assessment tool. RESULTS: Four RCTs met our inclusion criteria, including two
      RCTs comparing the efficacy of aroma inhalation as a treatment for pain and
      anxiety with that of placebo controls. Both studies showed that aroma inhalation
      was superior to placebo with respect to relieving pain and anxiety. The third
      study compared the effects of aroma inhalation on sleep quality with those of
      music therapy and showed that two the treatments exert equivalent effects on the
      above parameter, and the fourth trial compared the ability of aroma inhalation to
      reduce pain and anxiety with that of no treatment. The results showed that aroma
      inhalation can reduce pain but not anxiety. CONCLUSIONS: The evidence from the
      above trials is not sufficient to conclude that aromatherapy effectively relieves
      symptoms in patients with burns. However, the findings of the trials do not seem
      very plausible, and the trials themselves were of low quality and included only
      small numbers of patients. Studies that are adequately powered and feature better
      designs are needed to investigate the potential mechanisms underlying the effects
      of aroma therapy on pain and anxiety.

PMID- 29169702
TI  - Relationship between multidisciplinary critical care and burn patients survival:
      A propensity-matched national cohort analysis.
AB  - OBJECTIVE: The aims of this study are: firstly, to investigate if admission to
      specialized burn critical care units leads to better clinical outcomes; secondly,
      to elucidate if the multidisciplinary critical care contributes to this superior
      outcome. METHODS: A multi-centre cohort analysis of a prospectively collected
      national database of 1759 adult burn patients admitted to 13 critical care units
      in England and Wales between 2005 and 2011. Units were contacted via telephone to
      establish frequency and constitution of daily ward rounds. Critical care units
      were categorized into 3 settings: specialized burns critical care units,
      generalized critical care units and 'visiting' critical care units. Multivariate
      logistic regression analysis and propensity dose-response analysis were used to
      calculate risk adjusted mortality. RESULTS: Multivariate logistic regression
      analysis shows that admission to a specialized burn critical care service is
      independently associated with significant survival benefit compared to
      generalized critical care unit (adjusted OR for in-hospital death 1.81, [95% CI,
      1.24, 2.66]) and 'visiting' critical care services (adjusted OR for in-hospital
      death 2.24 [95% CI, 1.49, 3.38]). Further analysis using propensity dose-response
      analysis demonstrates that risk-adjusted in-hospital mortality rate decreased as
      the dose of multidisciplinary care increased, with an adjusted odds ratio of 1
      (specialized burn critical care units), 1.81 (generalized critical care units)
      and 2.24 ('visiting' critical care units). CONCLUSIONS: Admission to a
      specialized burn critical care service is independently associated with
      significant survival benefit. This is, at least in part, due to care being
      provided by a fully integrated multidisciplinary team.

PMID- 29169703
TI  - Laparoscopic partial nephrectomy: Comparative study of the transperitoneal
      pathway and the retroperitoneal pathway.
AB  - INTRODUCTION: Laparoscopic partial nephrectomy is the recommended treatment for
      tumours smaller than 4cm in cases where it is feasible. Depending on the location
      of the tumour, the transabdominal or direct retroperitoneal pathway may be
      considered. OBJECTIVE: To compare the transperitoneal (TPPN) and direct
      retroperitoneal (RPPN) partial nephrectomies performed between 2007 and 2016.
      MATERIAL AND METHODS: A retrospective study was conducted on 71 patients who
      underwent TPPN (42) or direct RPPN (29) partial nephrectomy. We evaluated the
      characteristics of the patients and tumours, including tumour complexity (PADUA,
      RENAL, C-index). We compared perioperational variables, including the
      complications between the 2 pathways. RESULTS: We found no differences in terms
      of age, sex, Charlson's score and BMI. A larger proportion of patients in the
      direct RPPN group had prior major abdominal surgery (7.1 vs. 24.1%; P=.043).
      There were no differences in tumour size, laterality, polarity or complexity in
      any of the assessed scores. There were significant differences in tumour location
      (anterior/middle/posterior) between the TPPN and RPPN groups (54.8/31/14.3 vs.
      3.4/13.8/82.8%; P<.001). There were no differences in the surgical time or length
      of stay. The TPPN group had a smaller urinary tract opening (4.8 vs. 27.6%;
      P=.007) and a higher percentage of haemostatic renorrhaphy (47.6 vs. 17.2%;
      P=.008). There were no differences in the need for warm ischaemia, in the changes
      in haemoglobin levels or in the glomerular filtration rate. The complication
      rates were similar for the two series. CONCLUSION: The two pathways show similar
      results in terms of renal function preservation, complications and oncological
      results. However, we recommend understanding both techniques and adapting the
      access type to the clinical case.

PMID- 29169704
TI  - Cumulative incidence and predictive factors of radiation cystitis in patients
      with localized prostate cancer.
AB  - PURPOSE: To determine the cumulative incidence of overall and severe radiation
      cystitis in a high volume cohort of patients and to investigate its potential
      predictive factors. METHODS: We have performed a retrospective analysis of
      clinical data from patients diagnosed with localized prostate cancer and treated
      with radiotherapy at our institution (June 2005-January 2013), and quantified the
      cumulative incidence of radiation cystitis. Cox regression analysis and Kaplan
      Meier curves were computed to evaluate the determinants of radiation cystitis.
      RESULTS: Data from 783 patients was retrieved (557 treated with primary
      radiotherapy, 188 with adjuvant and 38 with salvage). Median follow-up time was
      49 months (P25-P75: 31.8-69.3). At 5 years of follow-up, cumulative incidence of
      overall and severe radiation cystitis was 9.1 and 1.6%, respectively. No
      association was found between the incidence of radiation cystitis and age, tumor
      T stage, baseline PSA level, Gleason score, D'Amico risk classification,
      radiotherapy setting (primary versus adjuvant versus salvage) or radiation dose
      applied. CONCLUSIONS: Within our cohort, radiation cystitis is an uncommon
      complication of prostatic radiotherapy treatment, and severe cases requiring
      hospitalization are even more infrequent. We found no association between tumor
      characteristics, radiotherapy setting or radiation dose and the cumulative
      incidence of radiation cystitis.

PMID- 29169705
TI  - Clinical usefulness of random biopsies in diagnosis and treatment of non-muscle
      invasive bladder cancer: Systematic review and meta-analysis.
AB  - INTRODUCTION AND OBJECTIVE: This systematic review of the literature has been
      focused on determining the clinical usefulness of random bladder biopsies (RB) in
      the diagnosis of carcinoma in situ. A meta-analysis was performed to establish
      the clinic and pathological factors associated to positive biopsies. EVIDENCE
      ACQUISITION: A systematic review was performed using Pubmed/Medline database
      according to the PRISMA guidelines. Thirty-seven articles were included,
      recruiting a total of 12,657 patients, 10,975 were submitted to RB. EVIDENCE
      SYNTHESIS: The overall incidence of positive RB was 21.91%. Significant
      differences were found in the incidence of positive RB when patients were
      stratified according to urine cytology result, tumor multiplicity, tumor
      appearance, stage and grade. The results of the meta-analysis revealed that the
      presence of positive cytology, tumor multiplicity, non-papillary appearance
      tumors, stage T1 and histological grades G2 and G3 represent the risk factors to
      predict abnormalities in RB. CONCLUSIONS: The incidence of positive RB in
      patients with non-muscle invasive bladder cancer was 21.91%. The maximum
      usefulness of RB was observed when these are performed in a standardized way. The
      results of the meta-analysis showed that besides positive cytology and non
      papillary appearance tumors, tumor multiplicity and histological grades G2 and G3
      represent risk factors associated to positive RB, suggesting that the use of RB
      might be extensive to the intermediate risk group of the European Organization
      for Research and Treatment of Cancer (EORTC).

PMID- 29169706
TI  - Obesity, asthma, and vitamin D deficiency in pregnancy: Cause or consequence?

PMID- 29169707
TI  - Reply.

PMID- 29169708
TI  - Current study design labels are confusing! Call for consensus on better
      terminology that clearly reflects specific features.

PMID- 29169709
TI  - [Creation of expert centers on endometriosis].
AB  - Endometriosis is a frequent pathology with a high incidence of deep infiltrating
      endometriosis and complex forms that can affect 20% of patients with
      endometriosis. The incidence of infertility associated with endometriosis can
      reach 50%. The complexity of care requires the creation of expert centers working
      in networks with general practitioners. Criteria for defining these expert
      centers are being drawn up, based on structural criteria (multidisciplinary
      consultation meeting), links with medical assistance structures for procreation
      and activity criteria for severe and complex forms (number of interventions per
      center and per surgeon).

PMID- 29169710
TI  - Dysmetabolic iron overload syndrome (DIOS).
AB  - Dysmetabolic iron overload syndrome (DIOS) corresponds to mild increase in both
      liver and body iron stores associated with various components of metabolic
      syndrome in the absence of any identifiable cause of iron excess. It is
      characterized by hyperferritinemia with normal or moderately increased
      transferrin saturation, one or several metabolic abnormalities (increased body
      mass index with android distribution of fat, elevated blood pressure,
      dyslipidaemia, abnormal glucose metabolism, steatohepatitis), and mild hepatic
      iron excess at magnetic resonance imaging or liver biopsy. Alteration of iron
      metabolism in DIOS likely results from a multifactorial and dynamic process
      triggered by an excessively rich diet, facilitated by environmental and genetic
      cofactors and implying a cross-talk between the liver and visceral adipose
      tissue. Phlebotomy therapy cannot be currently considered as a valuable option in
      DIOS patients. Sustained modification of diet and life-style habits remains the
      first therapeutic intervention in these patients together with drug control of
      increased blood pressure, abnormal blood glucose and dyslipidaemia when
      necessary.

PMID- 29169711
TI  - The changing landscape of iron overload disorders at the beginning of the 21st
      century.

PMID- 29169712
TI  - [About twins: Epidemiological, genetic, and obstetrical aspects, specific risks,
      and outcome].
AB  - The incidence of twin pregnancies has increased steadily for the last 40 years
      due to assisted reproductive technology and increased maternal childbearing age.
      Multiple pregnancies, especially monochorionic twin pregnancies, carry a high
      risk for the mother and the fetuses and require close follow-up. Twins are
      exposed to a higher risk of perinatal anoxia, in utero fetal demise, preterm
      birth, congenital malformations, fetal growth restriction, and vascular
      complications. Compared to singletons, twins are at higher risk of perinatal
      mortality and impaired neurodevelopmental outcome, justifying a thorough follow
      up by pediatricians, including assessment and management of familial and
      psychosocial impact. This paper discusses the epidemiological, obstetrical, and
      genetic issues raised by twin pregnancies and reviews the data on the perinatal
      and neurological long-term outcomes of twins, as well as the psychosocial impact
      of multiple births on twins and their families.

PMID- 29169713
TI  - [Detection and codification of adverse drug reactions in a mother-child
      university hospital].
AB  - INTRODUCTION: In view of the underdeclaration of adverse drug reactions (ADRs),
      there is a need for optimizing their reporting. To improve our declaration, a
      pharmacovigilance program was started in 2006 at our center and measures were
      progressively started (weekly patient rounds, monthly report, etc.). The
      objectives of the study were to describe and compare the annual average incidence
      of the ADRs coded by the medical archivists from 1 April 1989 to 31 March 2010
      (period 1) and from 1 April 2010 to 31 March 2015 (period 2), to determine the
      therapeutic classes of drugs associated with ADRs according to age and determine
      the percentage of ADRs that are declared to Health Canada. METHODS: This was a
      nonexperimental, descriptive, and retrospective study in a mother-child
      university hospital. All the ADRs that arose with patients less than 18 years old
      during period 2 were included. The results of a previous study, conducted during
      period 1 were used. A Student t-test was used to compare the mean annual
      incidence and the average number of ADRs per year between the two periods.
      RESULTS: The average number of ADRs per year was 225.7+/-65.1 ADRs during period
      1 versus 429.6+/-52.1 ADRs during period 2 (P<0.01). The mean annual incidence of
      the ADRs was 1.64%+/-0.41% during period 1 versus 3.17%+/-0.43% during period 2
      (P<0.01). Throughout the study period, the mean annual gravity and mortality
      index were stable. The ADRs caused by antibiotics/antifungals, anticancer agents,
      opiates, and corticoids accounted for more than 50% of the total ADRs from 1989
      1990 to 2014-2015. Only 37% of the ADRs were declared to Health Canada during
      period 1 versus 41% during period 2. CONCLUSION: This study highlighted a
      progressive increase in the codification of the ADRs in the pediatric population
      from 1989-1990 to 2014-2015. No causal effect could be obtained between the
      measures that we implemented in 2006 and the improvement seen with the ADR
      codification, but we can reasonably suspect a positive impact.

PMID- 29169714
TI  - [Idiopathic nephrotic syndrome].
AB  - Nephrotic syndrome (NS) is defined by massive proteinuria and hypoalbuminemia,
      with resulting hyperlipidemia and edema. The most common cause of NS in children
      is idiopathic nephrotic syndrome (INS), also called nephrosis. Its annual
      incidence has been estimated to 1-4 per 100,000 children and varies with age,
      race, and geography. Many agents or conditions have been reported to be
      associated with INS such as infectious diseases, drugs, allergy, vaccinations,
      and malignancies. The disease may occur during the 1st year of life, but it
      usually starts between the ages of 2 and 7 years. INS is characterized by a
      sudden onset, edema being the major presenting symptom, but may rarely be
      discovered during a routine urine analysis. The disease may also be revealed by a
      complication such as hypovolemia, infection (pneumonia and peritonitis due to
      Streptococcus pneumoniae), deep-vein or arterial thromboses, and pulmonary
      embolism. Renal biopsy is usually not indicated in a child aged 1-10 years with
      typical symptoms and a complete remission with corticosteroids. Conversely, it is
      indicated in children under 1 year in case of macroscopic hematuria,
      hypertension, low C3 levels, persistent renal failure, or steroid resistance.
      Steroid therapy is applied in all children whatever the histopathology. Initial
      prednisone therapy in France consists of 60mg/m2 administered daily for 4 weeks
      (maximum dose, 60mg/day), followed by alternate-day prednisone with tapering
      doses. Eight-five to 90 % patients are steroid-responsive and may relapse, but
      the majority still responds to steroids over the subsequent courses. Only 1-3 %
      of patients who are initially steroid-sensitive subsequently become steroid
      resistant. Children with primary or secondary steroid-resistance are at risk of
      end-stage kidney disease. Symptomatic treatment includes salt restriction, fluid
      restriction when natremia is less than 125 meq/L, reduction of saturated fat and
      carbohydrates, calcium and vitamin D supplements, anticoagulation, and
      vaccination. Albumin infusions are only indicated in case of complications.
      Diuretics should be restricted to cases of severe edema, after hypovolemia has
      been corrected.

PMID- 29169715
TI  - [Perinatal care for extremely preterm infants. Considerations of the "risks in
      pregnancy" department].
AB  - Decisions regarding whether to initiate or forgo intensive care for extremely
      premature infants are often based on gestational age alone. However, other
      factors also affect the prognosis for these patients and must be taken into
      account. After a short review of these factors, we present the thoughts and
      proposals of the Risks and Pregnancy department. The proposals are to limit
      emergency decisions, to better take into account other factors than gestational
      age and prenatal predicted fetal weight in assessing the prognosis, to introduce
      multidisciplinary consultation in the evaluation and proposals that will be
      discussed with the parents, and to separate prenatal steroid therapy from
      decision-making regarding whether or not to administer intensive care.

PMID- 29169717
TI  - [Ten pitfalls to avoid when submitting a clinical research project to the French
      governmental grant program].

PMID- 29169716
TI  - [Body mass index charts of Algerian children and adolescents (6-18 years)].
AB  - The body mass index (BMI) is widely accepted as a measure of overweight and
      obesity in children. There are no BMI reference charts for Algerian children and
      adolescents. The purpose of this study was to construct BMI percentile curves
      appropriate for children aged 6-18 years in Algeria. The weight and height of
      7772 (54.9% girls) healthy schoolchildren from Constantine (eastern Algeria) were
      measured in 2008/2009. Weight and height for age curves based on the same sample
      were published previously. The BMI for age percentile curves were estimated in
      girls and boys separately using the LMS smoothing method. In both sexes, the
      median BMI increased with age. Girls had lower BMI values than boys before the
      age of 10 years but they were higher after this age until 18 years of age. Within
      the study population, the prevalence of overweight (including obesity) and
      obesity in girls and boys together was 13.7% and 3.0%, respectively, according to
      the International Obesity Task Force (IOTF) and 16.9% and 4.9% according to the
      World Health Organization (WHO) (2007). The median BMI curves of Algerian girls
      and boys were generally lower than those observed in other Arab countries.
      Compared with other references, the median BMI values of girls were lower than
      those of a Belgian Flemish population and WHO 2007 until 14 years of age and
      higher than the French reference between 7 and 18 years of age. The BMI values of
      Algerian boys were close to the Belgian (Flemish population), French and WHO 2007
      references between 6 and 9 years of age and generally lower thereafter. These BMI
      curves are complementary to the height and weight charts published previously for
      the assessment of growth in children and adolescents. They were developed
      according to international guidelines and could serve as a national reference.
      They could be used as a complement to the 0- to 5-year-old WHO 2006 standards.

PMID- 29169718
TI  - [Update on dietary management of cow's milk allergy].
AB  - Dietary management of cow's milk allergy is based on the elimination of all cow's
      milk proteins from the diet. For non-breastfed infants, the main dietetic move is
      the replacement of the standard infant formula with a formula for which the
      protein fraction has been modified. This formula can be based on hydrolyzed cow's
      milk proteins, rice proteins or amino acids. Monitoring the growth of these
      children is essential. The reintroduction of cow's milk, raw or heated, should
      always be made carefully and gradually. As the child grows and remains allergic,
      the use of heated (baked) milk substantially eases his/her feeding.

PMID- 29169719
TI  - Fracture Gap Reduction With Variable-Pitch Headless Screws.
AB  - PURPOSE: Fully threaded, variable-pitch, headless screws are used in many
      settings in surgery and have been extensively studied in this context, especially
      in regard to scaphoid fractures. However, it is not well understood how screw
      parameters such as diameter, length, and pitch variation, as well as technique
      parameters such as depth of drilling, affect gap closure. METHODS: Acutrak 2
      fully threaded variable-pitch headless screws of various diameters (Standard,
      Mini, and Micro) and lengths (16-28 mm) were inserted into polyurethane blocks of
      "normal" and "osteoporotic" bone model densities using a custom jig. Three
      drilling techniques (drill only through first block, 4 mm into second block, or
      completely through both blocks) were used. During screw insertion, fluoroscopic
      images were taken and later analyzed to measure gap reduction. The effect of
      backing the screw out after compression was evaluated. RESULTS: Drilling at least
      4 mm past the fracture site reduces distal fragment push-off compared with
      drilling only through the proximal fragment. There were no significant
      differences in gap closure in the normal versus the osteoporotic model. The Micro
      screw had a smaller gap closure than both the Standard and the Mini screws. After
      block contact and compression with 2 subsequent full forward turns, backing the
      screw out by only 1 full turn resulted in gapping between the blocks.
      CONCLUSIONS: Intuitively, fully threaded headless variable-pitch screws can
      obtain compression between bone fragments only if the initial gap is less than
      the gap closed. Gap closure may be affected by drilling technique, screw size,
      and screw length. Fragment compression may be immediately lost if the screw is
      reversed. CLINICAL RELEVANCE: We describe characteristics of variable-pitch
      headless screws that may assist the surgeon in screw choice and method of use.

PMID- 29169720
TI  - Treatment of Radial Head Fractures and Need for Revision Procedures at 1 and 2
      Years.
AB  - PURPOSE: Optimal treatment strategies for radial head fractures remain a subject
      of debate. We examined national practice patterns in the management of radial
      head fractures to determine rates of surgical treatment, type of surgery
      employed, and the incidence of reoperation. METHODS: Between 2007 and 2011, we
      identified patients with radial head fractures along with their associated
      injuries by International Classification of Diseases, Ninth Revision codes in a
      national database of orthopedic insurance records. For those who underwent
      surgery, the type of intervention was identified and each patient was observed to
      determine whether a subsequent procedure was needed by 1 and 2 years. Chi-square
      analysis was performed to make comparisons between groups. RESULTS: A total of
      58,404 radial head fractures were identified between 2007 and 2011; of these,
      2,981 underwent surgical treatment (5.1%). Rates of surgical intervention were
      significantly higher in the context of associated injuries. Among the 2,981
      radial head fractures treated surgically, 57.1% underwent open reduction internal
      fixation (ORIF), 37.9% were treated with radial head arthroplasty, and 4.9%
      underwent radial head excision. When the surgically treated radial head fracture
      was associated with a coronoid fracture, elbow dislocation, or proximal ulna
      fracture, 64.2%, 54.3%, and 47.2% were treated with arthroplasty, respectively,
      compared with 32.6%, 41.9%, and 52.6% treated with ORIF, respectively. After
      initial surgical treatment, 12.7% and 14.4% of radial head fractures that
      underwent ORIF required a secondary surgery at 1 and 2 years, respectively,
      compared with 8.6% and 10.7% of radial head arthroplasties and 8.3% and 8.4% of
      resections. CONCLUSIONS: Rates of arthroplasty were significantly higher in the
      context of associated injury, particularly in the setting of a coronoid fracture
      or elbow dislocation. Fractures initially treated with ORIF had a higher rate of
      revision surgery at both 1 and 2 years after the index procedure compared with
      arthroplasty. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

PMID- 29169721
TI  - Active Range of Motion Over Time in Patients With Obstetrical Brachial Plexus
      Palsy: A 10-Year Analysis.
AB  - PURPOSE: In our experience, and from the personal report of others, children with
      obstetrical brachial plexus palsy appear to lose some of their initially
      recovered active range of motion over the time in both operated and nonsurgical
      patients. This study investigates whether such a diminution of active movement
      occurs over time. METHODS: We performed a retrospective analysis of data from our
      obstetrical brachial plexus clinic. Between 1991 and 2000, 139 patients with a
      minimum follow-up of 10 years were included in the study. Patients were divided
      into a nonsurgical group (n = 42) and a group who underwent either primary or
      secondary brachial plexus reconstruction or both (n = 97). Fifteen joint
      movements were assessed at 2, 4 to 6, and 9 to 11 years of age and at later final
      follow-up using the Active Movement Scale. Repeated measures analysis using age
      at each visit as the repeated measures covariate was undertaken. RESULTS: Active
      movement scores were not diminished when patients were evaluated at the 10-year
      follow-up visit. CONCLUSIONS: The suggested loss of active range of motion over
      time is not demonstrated at 10-year follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Prognostic III.

PMID- 29169722
TI  - Management of Pisotriquetral Instability.
AB  - Pisotriquetral instability is an often-overlooked condition that can lead to
      ulnar-sided wrist pain and dysfunction. Various case series and biomechanical
      studies have been published regarding the diagnosis and treatment of this
      condition. We review current methods for examining, diagnosing, and treating
      pisotriquetral instability.

PMID- 29169723
TI  - Protective effects of allicin on 1,3-DCP-induced lipid metabolism disorder in
      HepG2 cells.
AB  - Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester), with quite a good
      range of hepatoprotective and antineoplastic properties, is a functional
      substance from garlic (Allium sativum L.) The purpose of this study was to
      provide evidence that allicin could protect 1,3-DCP-induced lipid metabolism
      disorder in HepG2 cells. Allicin reduced the accumulation of triglycerides (TG)
      and total cholesterol (TC) in 1,3-DCP-induced HepG2 cells. Allicin significantly
      increased the phosphorylation of AMP-activated protein kinase (AMPK) and down
      regulated the levels of sterol regulatory element binding protein-1 (SREBP-1) and
      sterol regulatory element binding protein-2 (SREBP-2) in 1,3-DCP-induced HepG2
      cells. Additionally, allicin had obvious recovery influence on the
      phosphorylation level of PKA and CREB in 1,3-DCP-induced HepG2 cells. These
      observations indicated that allicin alleviated lipid metabolism disorder induced
      by 1,3-DCP in HepG2 cells by regulating AMPK-SREBPs and PKA-CREB signaling
      pathways.

PMID- 29169724
TI  - BMSCs protect against liver injury via suppressing hepatocyte apoptosis and
      activating TGF-beta1/Bax singling pathway.
AB  - Many factors cause liver injury, including chronic consumption of alcohol,
      irregular use of drugs, excessive levels of arsenic in water. This study aims to
      investigate role of bone marrow-derived mesenchymal stem cells (BMSCs) in liver
      injury recovery and to explore mechanism. BMSCs and primary hepatocytes were
      isolated, cultured and identified. Hepatocyte model and hepatic fibrosis (HF)
      model were established using carbon tetrachloride (CCL-4). The role of BMSCs were
      investigated in both in vitro and in vivo levels. Cell proliferation was examined
      using MTT assay. Transforming growth factor-beta1 (TGF-beta1), Bcl-2 and Bax
      expression were detected using western blot and real-time PCR, respectively.
      Results indicated that BMSCs and primary hepatocytes were successfully isolated
      and identified, and hepatocyte model was successfully established. BMSCs and HGF
      treatment enhance viability of normal hepatocytes and hepatocyte injury model.
      Cell viability in BMSCs treatment and Bax-1 inhibitor treatment group was higher
      significantly compared to normal hepatocyte control and injury hepatocyte model,
      respectively (P<0.05). Bax-1 expression was significantly lower and Bcl-2 was
      significantly higher in Bax-1 inhibitor treatment and BMSCs treatment group
      compared to normal hepatocyte control (normal rats) and injury hepatocyte model
      (HF model), respectively (P<0.05). BMSCs significantly decreased ALT and AST
      levels compared to Saline group (P<0.05). In conclusion, function of BMSCs in
      liver injury was triggered by inhibiting hepatocyte apoptosis and leading cell
      proliferation through TGF-beta1/Bax singling pathway. Our study proved protective
      role of BMSCs against liver injury via TGF-beta1/Bax pathway, which would enrich
      application of BMSC in clinical.

PMID- 29169725
TI  - Ginsenoside Rg3 inhibits colorectal tumor growth via down-regulation of
      C/EBPbeta/NF-kappaB signaling.
AB  - Colorectal cancer (CRC), the third most frequent occurred cancer, is associated
      with high mortality and extremely poor prognosis. Ginsenoside Rg3 (Rg3), one of
      the pharmacologically active components of traditional Chinese herbal medicine
      Panax ginseng, exerts antitumor effects against several types of cancer growth,
      including colorectal cancer. However, the detailed molecular mechanisms and
      particularly the signaling pathways that are decisive in this process are not yet
      fully elucidated. The present study was carried out to determine the antitumor
      effects of Rg3 using human colorectal cells in vitro and Xenograft tumor model of
      human colon cancer in vivo. We found that Rg3 effectively suppressed the
      proliferation of cancer cells in three human colorectal cancer cell lines
      (HCT116, HT29, SW480). In addition, intraperitoneal injection of Rg3 for 3 weeks
      significantly inhibited the growth of xenografts in nude mice. Furthermore, we
      determined the potential underlying mechanisms for these actions. Treatment with
      Rg3 significantly inhibited the transactivation of C/EBPbeta and NF-kappaB, as
      well as the association of C/EBPbeta with p65-NFkappaB in nucleus. However, when
      SW-480 cells were co-transfected with C/EBPbeta, or pretreatment with TNFalpha,
      Rg3 failed to inhibit tumor growth. Taken together, our results revealed a robust
      anti-tumor effect of Rg3, which is mediated by inhibition of C/EBPbeta/NF-kappaB
      signaling.

PMID- 29169726
TI  - Piperine (PP) enhanced mitomycin-C (MMC) therapy of human cervical cancer through
      suppressing Bcl-2 signaling pathway via inactivating STAT3/NF-kappaB.
AB  - Piperine (PP), an alkaloid from black and long peppers (Piper nigrum Linn &Piper
      longum Linn), exhibits antitumor activities in vitro and in vivo. We investigated
      the ability of piperine (PP) to reverse the drug resistance of human cervical
      cancer cells. In our study, the cervica cancer cells resistant to mitomycin-C
      (MMC) treatment were used. We found the growth inhibitory effects of piperine on
      human cervical cancer cell, which were resistant to MMC. Piperine and MMC co
      treatment resulted in a dose-dependent suppression of the cell proliferation.
      Decreasing of phosphorylated-signal transducer and activator of transcription (p
      STAT3) was linked to the suppression of p65 by PP and MMC combinational
      treatment. Additionally, the presence of PP potentiated the effects of MMC on
      apoptosis induction in cervical cancer cells with drug resistance, which was
      dependent on Bcl-2 inhibition. The pro-apoptotic proteins of Bax and Bid were up
      regulated, accompanied with Caspase cleavage. Moreover, in mice xenograft models,
      the combined therapy inhibited tumor growth compared to the PP or MMC mono
      therapy group. Our data indicated a novel therapeutic strategy of PP to
      potentiate MMC-induced anti-tumor effect on cervical cancer cells with drug
      resistance through blocking p-STAT3/p65 and Bcl-2 activation.

PMID- 29169727
TI  - Effects of separate and concurrent supplementation of Nano-sized clinoptilolite
      and Nigella sativa on oxidative stress, anti-oxidative parameters and body weight
      in rats with type 2 diabetes.
AB  - OBJECTIVES: The objective of this study was to investigate the effects of
      separate and concurrent supplementation of natural nano-sized clinoptilolite
      (NCLN) and Nigella sativa (NS) on oxidative stress (OS), anti-oxidative
      parameters and body weight (BW) in high-fat-diet (HFD)/streptozotocin (STZ)
      induced diabetic rats. METHODS: In this experimental study, 42 male Wistar rats
      were divided into diabetic (n=36) and non-diabetic (n=6) groups. The diabetic
      group (DG) was fed with a HFD for one month, then injected with intra-peritoneal
      single dose STZ (35 mg/kg BW). The DG was divided into 4 subgroups: [1] control
      (DC), [2] NS 1%/food, [3] NCLN 2%/food, [4] NS 1%/food + NCLN 2%/food. At the end
      of the 7th week, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione
      peroxidase (GPX) levels and total antioxidant capacity (TAC) were measured.
      RESULTS: The MDA level was decreased in the NCLN (p = 0.011) and NCLN+NS (p =
      0.007) groups compared to the DC group. The GPX level increased in the NS and
      NCLN groups compared to the DC group (p = 0.014 and p = 0.034). In addition, the
      level of TAC demonstrated increase in the untreated DG and NS groups, as compared
      to the normal control (NC) group (pDC = 0.031 and pNS = 0.024). Moreover, in the
      NS+NCLN group, the level of SOD decreased in comparison to the NS and NCLN groups
      (p < 0.01). At the end of the 7th week, BW decreased in the diabetic subgroups in
      comparison to the NC group. Treatment with NS and/or NS+NCLN insignificantly
      prevented severe weight loss in the fifth week of the treatment. CONCLUSIONS:
      According to results, separate supplementation of NS and NCLN was more beneficent
      on anti-oxidative parameters than concurrent supplementation of NS and NCLN.

PMID- 29169728
TI  - Morphological analysis of mitochondria for evaluating the toxicity of alpha
      synuclein in transgenic mice and isolated preparations by atomic force
      microscopy.
AB  - A key molecular event in the pathogenesis of Parkinson's disease is mitochondrial
      damage caused by alpha-synuclein (alpha-syn). Mitochondria mediates both necrosis
      and apoptosis, which are associated with morphological changes. However, the
      mechanism by which alpha-syn alters mitochondrial morphology remains unclear. To
      address this issue, we investigated mitochondrial permeability transition pore
      (mPTP) opening and changes in cardiolipin (CL) levels in mitochondria isolated
      from the brain of Thy1alpha-syn mice. Cytoplasmic cytochrome C and cleaved
      caspase-3 protein levels were upregulated in the brain of transgenic mice.
      Morphological analysis by atomic force microscopy (AFM) suggested a correlation
      between mitochondrial morphology and function in these animals. Incubation of
      isolated mitochondria with recombinant human alpha-synuclein N terminus (alpha
      syn/N) decreased mitochondrial CL content. An AFM analysis showed that alpha
      syn/N induced mitochondrial swelling and the formation of pore-like structures,
      which was associated with decreased mitochondrial transmembrane potential and
      complex I activity. The observed mitochondrial dysfunction was abrogated by
      treatment with the mPTP inhibitor cyclosporin A, although there was no recovery
      of CL content. These results provide insight into the mechanism by which alpha
      syn/N directly undermines mitochondrial structure and function via modulation of
      mPTP opening and CL levels, and suggests that morphological analysis of isolated
      mitochondria by AFM is a useful approach for evaluating mitochondrial injury.

PMID- 29169729
TI  - miR-193b-3p possesses anti-tumor activity in ovarian carcinoma cells by targeting
      p21-activated kinase 3.
AB  - miR-193b-3p was found to be downregulated and contributed to ovarian cancer (OC)
      progression. In the present study, we aimed to study the detailed role of miR
      193b-3p in the development of OC and the underlying molecular mechanism. The
      results showed that miR-193b-3p was downregulated while PAK3 was upregulated in
      OC cells. Ectopic expression of miR-193b-3p and PAK3 knockdown repressed cell
      proliferation, promoted paclitaxel-induced cytotoxicity, and reinforced
      paclitaxel-mediated caspase-3 activity increase in OC cells. Notably, miR-193b-3p
      was identified to directly target PAK3 and suppressed PAK3 expression. Moreover,
      enforced expression of PAK3 partially overturned the effects of miR-193b-3p on OC
      cell proliferation and paclitaxel sensitivity. In conclusion, miR-193b-3p
      possessed anti-tumor activity in OC through inhibiting cell proliferation and
      enhancing paclitaxel sensitivity by targeting PAK3. Therefore, our study
      suggested that the miR-193b-3p/PAK3 axis might be a potential novel therapeutic
      target for OC.

PMID- 29169730
TI  - Acute bilateral common carotid arteries occlusion (2VO) alone could not be a
      proper method for induction of ischemia in rats.

PMID- 29169731
TI  - A composition of medicinal plants with an enhanced ability to suppress microsomal
      lipid peroxidation and a protective activity against carbon tetrachloride-induced
      hepatotoxicity.
AB  - Treatment of liver injury induced by various toxicants represents a serious
      clinical challenge. Here, we utilized the ability of natural agents to inhibit
      microsomal lipid peroxidation (LPO) as the in-vitro screening paradigm for
      selecting efficacious tissue-protective combinations of cooperatively acting
      medicinal plants. Based on screening of 70 water-ethanol extracts obtained from
      different parts of 65 plants we prepared a highly active phytocomposition (PC-1)
      containing oregano (Origanum vulgare), wild thyme (Thymus serpyllum) and
      coltsfoot (Tussilago farfara) aerial parts, valerian (Valeriana officinalis)
      leaves and little-leaf linden (Tilia cordata) flowers. PC-1 extract exhibited the
      strongest anti-PLO and antihemolytic effects in vitro compared to those of the
      individual plants and other compositions tested. Using luciferase reporter assay
      and Western blotting in HepG2 human hepatocellular carcinoma cells, we found that
      PC-1 extract activated the Nrf2/antioxidant response element signaling pathway
      more effectively than the extracts of other phytocompositions. Importantly, oral
      administration of PC-1 extract (100-200 mg/kg) markedly ameliorated liver injury
      in rats acutely or chronically intoxicated by carbon tetrachloride. This was
      evidenced by improved liver histology, blood chemistry parameters, and microsomal
      LPO status and superoxide dismutase activity. In addition, treatment with PC-1
      extract salvaged the osmotic resistance of erythrocytes in carbon tetrachloride
      intoxicated rats. Collectively, these data support the strategy of in-vitro plant
      selection for developing efficacious tissue-protective phytocompositions.

PMID- 29169732
TI  - MicroRNA-4465 suppresses tumor proliferation and metastasis in non-small cell
      lung cancer by directly targeting the oncogene EZH2.
AB  - MicroRNA-26 (miR-26) has been reported to be connected with tumor progression.
      MicroRNA-4465 (miR-4465) was one member of miR-26 family, however, the role of
      miR-4465 in non-small cell lung cancer (NSCLC) was unknown. This study was aimed
      to explore the function of miR-4465 and investigate whether miR-4465 can be a
      potential target for treating human NSCLC. QRT-PCR was applied to evaluate the
      miR-4465 expression levels in NSCLC cells. Then, we demonstrated the role of miR
      4465 in NSCLC cells biological characteristics through detecting proliferation,
      migration and invasion. Luciferase reporter assay and TargetScan were applied to
      explore the potential target gene of miR-4465. In this study, we found that the
      miR-4465 expression levels in NSCLC cell lines were significantly reduced when
      compared to the normal human bronchial epithelial cell lines. And, over
      expression of miR-4465 could restrain the proliferation, migration and invasion
      of NSCLC. Moreover, MiR-4465 reduced EZH2 protein expression through the binding
      sites in 3' -UTR of the EZH2 mRNA, indicating EZH2 may be a direct target gene of
      miR-4465. Conclusively, miR-4465 suppressed cancer cells proliferation and
      metastasis by directly targeting the oncogene EZH2 and it may serve as a new
      potential therapeutic target in NSCLC.

PMID- 29169733
TI  - Use of Copaifera multijuga for acute corneal repair after chemical injury: A
      clinical, histopathological and toxicogenetic study.
AB  - Copaiba oil is widely used in medicine, but there are no reports regarding its
      application in ophthalmology. Therefore, the objective of this study was to
      evaluate the clinical, histopathological and toxicogenetic effects of eye drops
      containing 0.1 and 0.5% of Copaifera multijuga Hayne oil on superficial corneal
      ulcers induced with alkali in the left eye of rats. For histological analysis,
      the percent reduction in ulcers and thickness of the corneal epithelium and
      stroma were evaluated 48 and 72 h after ulcer induction. Additionally,
      neovascularization and polymorphonuclear infiltration were classified in the
      stroma. The bone marrow micronucleus test was used for toxicogenetic assessment.
      None of the animals exhibited clinical signs of immediate ocular discomfort after
      instillation and the eye drops were harmless to the ocular surface. There was a
      significant difference in percent ulcer reduction and corneal stroma thickness
      between animals treated with the C. multijuga eye drops and untreated animals
      with corneal injury and the negative control, respectively, suggesting a healing
      effect of the oleoresin. Analysis of the thickness of the corneal epithelium at
      the two time points showed that the eye drops formulated did not significantly
      reduce the damage caused by alkali. The same was observed for the treatments with
      the reference drugs. No difference in stromal neovascularization or inflammatory
      infiltration was observed between the treated groups. The toxicogenetic results
      revealed the absence of cytotoxicity and genotoxicity of the treatments. In
      conclusion, the C. multijuga eye drops did not cause damage to the ocular surface
      under the present experimental conditions and corneal epithelization was similar
      to the conventional treatments. These results indicate that eye drops containing
      C. multijuga oleoresin are a promising option for the treatment of superficial
      keratitis.

PMID- 29169734
TI  - Vectored gene delivery for lifetime animal contraception: Overview and hurdles to
      implementation.
AB  - There is a need for permanent, non-surgical methods of contraception for many
      animal species. Here we discuss the hypothesis that transgene-mediated expression
      of fertility inhibiting molecules such as monoclonal antibodies, ligands for cell
      surface receptors, receptor decoys, or small RNAs can provide such a method,
      which we term vectored contraception. We outline the technologies involved,
      progress made, and discuss challenges to implementation.

PMID- 29169735
TI  - Associations of Clinically Relevant Levels of Depressive Symptoms and
      Antidepressant Use With Mortality in African American Health.
AB  - BACKGROUND: The Institute of Medicine has highlighted unequal treatment for
      African American individuals in health care. We examined the association of
      underuse of antidepressants in African American individuals with increased
      mortality. METHODS: We conducted a longitudinal cohort study in Metropolitan St
      Louis, Missouri, in a population-based study of community-dwelling African
      American individuals, aged 52 to 68 years. Medication evaluations and clinically
      relevant levels of depressive symptoms (CRLDS) assessments occurred in 2000 and
      2004. The analytic sample included 830 (of 853 total, 97%) participants with
      complete data. CRLDS was defined as >=9 on the 11-item Center for Epidemiologic
      Studies Depression scale. Antidepressant use was determined by in-home medication
      recording and in-center coding. Participants were placed into 4 exposure
      categories: persistent CRLDS-no antidepressant (n = 69); intermittent CRLDS-no
      antidepressant (n = 123); antidepressant treatment (n = 110); and no CRLDS-no
      antidepressant (n = 528). Logistic regression with backwards elimination of the 9
      identified potential confounders was used to examine associations of exposures
      with all-cause mortality over 6 years (2004-2010). Five sensitivity analyses
      investigated robustness of the primary findings. RESULTS: The antidepressant
      group was independently associated with reduced mortality compared with the
      persistent-no antidepressant group (odds ratio [OR] 0.19, 95% confidence interval
      [CI] 0.08-0.44). Sensitivity analyses showed no substantive differences from the
      primary model; one indicated that the persistent CRLDS-no antidepressant group
      experienced significantly increased mortality compared with the no CRLDS-no
      antidepressant group (OR 2.12, 95% CI 1.10-4.09), whereas the intermittent-no
      antidepressant group did not (OR 0.83, 95% CI 0.44-1.58). CONCLUSIONS: These
      results highlight that underuse of antidepressants in African American
      individuals is associated with increased mortality.

PMID- 29169737
TI  - Determining the Physician-to-Patient Ratio in Post-Acute/Long-Term Care Using an
      Economic Model.

PMID- 29169738
TI  - Snoezelen Therapy as an Intervention to Reduce Agitation in Nursing Home Patients
      With Dementia: A Pilot Study.

PMID- 29169736
TI  - Examining the Effects of Age on Health Outcomes of Chronic Obstructive Pulmonary
      Disease: Results From the Genetic Epidemiology of Chronic Obstructive Pulmonary
      Disease Study and Evaluation of Chronic Obstructive Pulmonary Disease
      Longitudinally to Identify Predictive Surrogate Endpoints Cohorts.
AB  - RATIONALE: The prevalence of chronic obstructive pulmonary disease (COPD) and its
      associated comorbidities increase with age. However, little is understood about
      differences in the disease in patients over 65 years of age compared with younger
      patients. OBJECTIVES: To determine disease characteristics of COPD and its impact
      in older patients compared with younger patients. METHODS: We examined baseline
      characteristics of patients with COPD (global obstructive lung disease stage II
      IV) in 2 large cohorts: Genetic Epidemiology of COPD Study (COPDGene) and
      Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints
      (ECLIPSE). We compared demographics, indices of disease severity, prevalence of
      comorbidities, exacerbation frequency, and quality of life scores in patients
      >=65 years of age vs patients <65 years of age. We also tested for associations
      of age with disease characteristics and health outcomes. RESULTS: In the COPDGene
      cohort, older patients (n = 1663) had more severe disease as measured by forced
      expiratory volume in 1 second (1.22 vs 1.52 L, P < .001), use of long-term oxygen
      therapy (35% vs 22%, P < .001), 6-minute walk distance (355 vs 375 m, P < .001),
      and radiographic evidence of emphysema (14% vs 8%, P < .001) and air trapping
      (47% vs 36%, P < .001) and were more likely to have comorbidities compared with
      younger patients (n = 2027). Similarly, in the ECLIPSE cohort, older patients (n
      = 1030) had lower forced expiratory volume in 1 second (1.22 vs 1.34 L, P <
      .001), greater use of long-term oxygen therapy (7% vs 5%, P = .02), shorter 6-
      minute walk distance (360 vs 389 m, P < .001), and more radiographic evidence of
      emphysema (17% vs 14%, P = .009) than younger patients (n = 1131). In adjusted
      analyses of both cohorts, older age was associated with decreased frequency of
      exacerbations [odds ratio = 0.52, 95% confidence interval (CI) = 0.43-0.64 in
      COPDGene, odds ratio = 0.79, 95% CI = 0.64-0.99 in ECLIPSE] and a better quality
      of life (lower St. Georges respiratory questionnaire score) (beta = -8.7, 95% CI
      = -10.0 to -7.4 in COPDGene, beta = -4.4, 95% CI = -6.1 to -3.2 in ECLIPSE).
      CONCLUSIONS: Despite greater severity of illness, older patients with COPD had
      better quality of life and reported fewer exacerbations than younger patients.
      Although this observation needs to be explored further, it may be related to the
      fact that older patients change their expectations and learn to adapt to their
      disease.

PMID- 29169739
TI  - Response to the Letter to the Editor by Simon D. Smith "Recall Tests Can Be
      Effective to Detect Mild Cognitive Impairment: A Response to Tsoi and
      Colleagues".

PMID- 29169742
TI  - A Decade of JAMDA.

PMID- 29169741
TI  - Utilization of Antibiotics in Long-Term Care Facilities in British Columbia,
      Canada.
AB  - BACKGROUND: Antibiotic use is highly prevalent in long-term care facilities
      (LTCFs); a resident's annual exposure to at least 1 course of antibiotic is
      approximately 50% to 80%. The objective of this study was to understand the
      extent of antibiotic use in the population of residents in British Columbia's
      (BC) LTCFs from 2007 to 2014. METHODS: Antibiotic prescription data for LTCF
      residents was extracted from the central prescription database and linked to the
      physician billing plan to obtain antibiotic indication. Total defined daily dose
      (DDD) per 1000 residents per day was calculated. RESULTS: Our database had 381
      LTCFs with an average of nearly 24,694 residents annually and 419,036 antibiotic
      prescriptions. Antibiotic utilization did not change dramatically between 2007
      and 2014, ranging from 39.2 in 2007 to 35.2 DDD per 1000 residents per day in
      2014. Although usage of most antibiotics declined, use of moxifloxacin,
      amoxicillin-clavulanate, doxycycline, and amoxicillin increased significantly.
      The indication most frequently linked to prescription was urinary tract infection
      (6.58 DDD per 1000 residents per day), with nitrofurantoin, ciprofloxacin, and
      trimethoprim/sulfamethoxazole being the most commonly prescribed agents. This was
      followed closely by prescriptions for respiratory infections (5.34 DDD per 1000
      residents per day), with moxifloxacin being the most commonly prescribed
      antibiotic, primarily for upper respiratory tract infection (URTI), whereas
      doxycycline is used commonly for lower respiratory tract infection. Duration of
      antibiotic therapy in LTCF residents has decreased significantly from 9.29 days
      to 7.3 days per prescription in 2014. CONCLUSION: Antibiotic use in LTCFs is high
      relative to the general population. Our study underscores that stewardship in
      LTCFs should continue to focus on length of treatment, appropriate detection of
      urinary tract infections, and avoidance of treating URTIs with antibiotics.

PMID- 29169743
TI  - Overview of Two Different Nursing Home Health Systems: Examples From France and
      the United States.

PMID- 29169740
TI  - Redefining Cut-Points for High Symptom Burden of the Global Initiative for
      Chronic Obstructive Lung Disease Classification in 18,577 Patients With Chronic
      Obstructive Pulmonary Disease.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be
      classified into groups A/C or B/D based on symptom intensity. Different threshold
      values for symptom questionnaires can result in misclassification and, in turn,
      different treatment recommendations. The primary aim was to find the best fitting
      cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD)
      symptom measures, with an modified Medical Research Council dyspnea grade of 2 or
      higher as point of reference. METHODS: After a computerized search, data from 41
      cohorts and whose authors agreed to provide data were pooled. COPD studies were
      eligible for analyses if they included, at least age, sex, postbronchodilator
      spirometry, modified Medical Research Council, and COPD Assessment Test (CAT)
      total scores. MAIN OUTCOMES: Receiver operating characteristic curves and the
      Youden index were used to determine the best calibration threshold for CAT, COPD
      Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores.
      Following, GOLD A/B/C/D frequencies were calculated based on current cut-points
      and the newly derived cut-points. FINDINGS: A total of 18,577 patients with COPD
      [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most
      patients had a moderate or severe degree of airflow limitation (GOLD spirometric
      grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best
      calibration threshold for CAT total score was 18 points, for COPD Clinical
      Questionnaire total score 1.9 points, and for St. Georges Respiratory
      Questionnaire total score 46.0 points. CONCLUSIONS: The application of these new
      cut-points would reclassify about one-third of the patients with COPD and, thus,
      would impact on individual disease management. Further validation in prospective
      studies of these new values are needed.

PMID- 29169745
TI  - Corrigendum to "Effects of coffee processing residues on anaerobic microorganisms
      and corresponding digestion performance" [Bioresour. Technol. 245 (2017) 714
      723].

PMID- 29169744
TI  - The neuropathology of multiple system atrophy and its therapeutic implications.
AB  - Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized
      by the abnormal accumulation of toxic forms of the synaptic protein alpha
      synuclein (alpha-syn) within oligodendrocytes and neurons. The presence of alpha
      syn within oligodendrocytes in the form of glial cytoplasmic inclusions is the
      diagnostic hallmark of MSA. However, it has been postulated that alpha-syn is
      produced in neurons and propagates to oligodendrocytes, where unknown mechanisms
      lead to its accumulation. The presence of alpha-syn within neurons in MSA has not
      been so extensively studied, but it may shed light into neuropathological
      mechanisms leading to oligodendroglial accumulation. Here we summarize the
      principal neuropathological events of MSA, and discuss how a deeper knowledge of
      these mechanisms may help develop effective therapies targeting alpha-syn
      accumulation and spreading.

PMID- 29169746
TI  - Simulations of simple Bovine and Homo sapiens outer cortex ocular lens membrane
      models with a majority concentration of cholesterol.
AB  - The lipid composition of bovine and human ocular lens membranes has been probed,
      and a variety of lipids have been found including phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), sphingomyelin (SM), and cholesterol (CHOL) with
      cholesterol being present in particularly high concentrations. In this study, we
      use the all-atom CHARMM36 force field to simulate binary, ternary, and quaternary
      mixtures as models of the ocular lens. High concentration of cholesterol, in
      combination with different and varying diversity of phospholipids (PL) and
      sphingolipids (SL), affect the structure of the ocular lens lipid bilayer. The
      following analyses were done for each simulation: surface area per lipid,
      component surface area per lipid, deuterium order parameters (SCD), electron
      density profiles (EDP), membrane thickness, hydrogen bonding, radial distribution
      functions, clustering, and sterol tilt angle distribution. The SCD show
      significant bilayer alignment and packing in cholesterol-rich bilayers. The EDP
      show the transition from liquid crystalline to liquid ordered with the addition
      of cholesterol. Hydrogen bonds in our systems show the tendency for
      intramolecular interactions between cholesterol and fully saturated lipid tails
      for less complex bilayers. But with an increased number of components in the
      bilayer, the acyl chain of the lipids becomes a less important characteristic,
      and the headgroup of the lipid becomes more significant. Overall, cholesterol is
      the driving force of membrane structure of the ocular lens membrane where
      interactions between cholesterol, PL, and SL determine structure and function of
      the biomembrane. The goal of this work is to develop a baseline for further study
      of more physiologically realistic ocular lens lipid membranes. This article is
      part of a Special Issue entitled: Emergence of Complex Behavior in Biomembranes
      edited by Marjorie Longo.

PMID- 29169747
TI  - The perks of being a female in the TAVI era.

PMID- 29169748
TI  - Ascending aortic size in aortic coarctation depends on aortic valve morphology:
      Understanding the bicuspid valve phenotype.
AB  - BACKGROUND: In roughly half of patients with coarctation of the aorta (CoA), the
      aorta may be enlarged. It is uncertain whether enlargement is independent of
      aortic valve morphology. We sought to compare aortic size in CoA with a tricuspid
      valve (TAV) to those with bicuspid aortic valve (BAV). METHODS: Sixty-eight CoA
      patients and 20 healthy controls with prior cardiac magnetic resonance (CMR)
      imaging were included. CMR was retrospectively reanalyzed to measure aortic root
      and mid-ascending aorta. The maximum aortic diameter was compared between CoA
      with TAV, CoA with BAV, and control groups. RESULTS: CoA with TAV patients (n=27)
      had smaller aortic root diameters than CoA with BAV (n=41) (32+/-4.9 vs. 37+/
      5.8mm, p=0.001), despite being older (40 vs. 32years, p=0.01). Similarly, TAV CoA
      patients had a smaller mid-ascending aortic diameter (28+/-4.5 vs. 33+/-6.9mm,
      p=0.019) than BAV patients. TAV CoA was similar to controls in all metrics.
      Twenty-four patients (35%) with CoA had dilated aortas (>37mm), of which 79% had
      BAV. A history of hypertension did not predict larger aortic root or mid
      ascending aortic dimensions. CONCLUSIONS: In patients with CoA, TAV is associated
      with smaller aortic size compared to those with BAV, and similar to healthy
      controls. Aortic size in CoA is independent of hypertension. Therefore,
      aortopathy associated with BAV is likely a reflection of the BAV phenotype rather
      than CoA or its physiologic effects. This distinction may have implications for
      the frequency and types of monitoring and treatment of CoA patients.

PMID- 29169749
TI  - Comprehensive assessment of sex hormones in Takotsubo syndrome.
AB  - BACKGROUND: The detailed pathomechanism of Takotsubo syndrome (TS) is still
      elusive. Due to the predominance of postmenopausal females, a potential role of
      sex hormones has been suggested. However, the limited available data are
      contradictory. The aim of this study was to comprehensively assess the role of
      sex hormone levels in a large cohort of TS patients. METHODS: Serum samples of 57
      female TS patients and 57 female patients with myocardial infarction (MI),
      matched for age (+/-2years) and repolarization disturbances were analyzed for
      estradiol (E2), estrone (E1), testosterone and androstenedione using liquid
      chromatography-tandem mass spectrometry. RESULTS: There was no difference
      concerning the concentrations of E1 [pmol/l (IQR): 89.1 (62.5, 132.0) vs. 98.8
      (63.3, 156.0), p=0,441], testosterone [nmol/l (IQR): 0.67 (0.46, 1.00) vs. 0.80
      (0.49, 1.08), p=0.382] and androstenedione [nmol/l (IQR): 2.03 (1.57, 3.11) vs.
      2.98 (1.48, 5.27), p=0.244] between female TS and MI patients. Regarding E2, the
      majority of patients demonstrated concentrations below the detection limit of
      30pmol/l (TS: n=41/54, 75.9%; MI: n=32/53, 60.4%; p=0.078). The remaining
      individuals with detectable E2 concentrations did not show a significant
      difference between TS and MI patients [pmol/l (IQR): 40.5 (33.0, 53.3) vs. 54.1
      (37.9, 60.9); p=0.20]. CONCLUSIONS: Altered sex hormone levels, especially an
      estradiol deficiency, could not be identified as a risk factor for TS.

PMID- 29169750
TI  - Bicuspid aortic valve: A complex aortopathy rather than a simple valvulopathy.

PMID- 29169751
TI  - Selecting the right defibrillator in the younger patient: Transvenous, epicardial
      or subcutaneous?
AB  - The advent of the subcutaneous implantable cardioverter-defibrillator (SQ-ICD)
      provides an alternative to transvenous and epicardial ICD therapy. Particularly
      germane to the young patient with congenital heart disease or inheritable
      arrhythmia syndromes, the SQ-ICD may be ideal for those who do not require
      permanent cardiac pacing. The serious complications associated with transvenous
      ICD systems are largely driven by the intravascular components of these devices
      and are avoided by this extravascular technique. Multiple clinical trials have
      shown that SQ-ICDs are effective in detecting and terminating ventricular
      arrhythmias, yet nuanced issues must be considered, especially in the context of
      congenital cardiovascular anomalies. This review aims to contextualize the role
      of this technology in contrast with traditional ICDs, and provide a logical
      approach to appropriate device selection.

PMID- 29169752
TI  - Vigorous exercise in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: We aimed to investigate if history of vigorous exercise was
      associated with changes in left ventricular morphology, left ventricular function
      and ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy genotype
      positive, phenotype negative (Genotype+ LVH-) and in phenotype positive (HCM
      LVH+). METHODS: In this cross sectional study we included 187 subjects (age 49+/
      16years, 89(48%) female, 121(65%) HCM LVH+ and 66 (35%) Genotype+ LVH-) who
      answered a questionnaire on physical activity history. Exercise >=6 metabolic
      equivalents was defined as vigorous. Subjects with a history of vigorous exercise
      >=4h/week during >=6years were defined as athletes. All underwent
      echocardiography and Holter monitoring. VAs were defined as aborted cardiac
      arrest, sustained or non-sustained ventricular tachycardia. RESULTS: In both
      Genotype+ LVH- and HCM LVH+, lifetime vigorous exercise correlated with larger
      left ventricular end-diastolic volume (rho 0.44 and 0.38 respectively, both
      p<0.001). Lifetime vigorous exercise correlated with increased left ventricular
      mass in Genotype+ LVH- (rho 0.28, p=0.03), but not in HCM LVH+ (p=0.53). Left
      ventricular systolic function was similar between athletes and non-athletes in
      Genotype+ LVH- and HCM LVH+. HCM LVH+ athletes had lower E/e' (p=0.03) and higher
      e' (p=0.02) compared to non-athletes, while this difference was not observed in
      Genotype+ LVH-. Lifetime vigorous exercise was similar among HCM LVH+ with and
      without VAs (p=0.89). CONCLUSIONS: Increased lifetime vigorous exercise was
      associated with larger left ventricular volumes in hypertrophic cardiomyopathy,
      but correlated to left ventricular mass only in Genotype+ LVH-. Vigorous exercise
      was associated with favorable diastolic function in HCM LVH+, and was not
      associated with VAs.

PMID- 29169753
TI  - Trends and predictors of non-cardiovascular death in patients hospitalized for
      acute heart failure.
AB  - BACKGROUND: Little information is available on non-cardiovascular (CV) death in
      acute heart failure (AHF) patients. The present study determined the incidence,
      time course, and factors associated with long-term non-CV death in AHF patients
      in a real-world setting. METHODS: The ATTEND registry, a nationwide, prospective
      observational multicenter cohort study, included 4842 consecutive patients
      hospitalized for AHF. The primary endpoint of the present study was non-CV death.
      RESULTS: Median follow-up duration from admission was 513 (range, 385-778) days.
      Over the study period, 1183 patients died; 356 deaths (30.1%) were non-CV
      related. The proportion of non-CV deaths increased in the later follow-up phase
      (0-180days, 26.7%; 181-360days, 38.4%; >360days, 36.6%, p<0.001). After
      adjustment for all variables at baseline, age (hazard ratio [HR] 1.6 per decade,
      p<0.001) and non-cardiac comorbidities including chronic obstructive pulmonary
      disease (HR 1.58, p=0.003), history of stroke (HR 1.44, p=0.011), renal
      insufficiency (HR 1.07, per 10ml/min/1.73m2 decrease in estimated glomerular
      filtration, p=0.015), and hemoglobin (HR 1.15 per 1.0g/dl decrease, p<0.001) were
      strongly associated with non-CV death. Other predictors included ischemic
      etiology (HR 1.33, p=0.023), prior hospitalization for heart failure (HR 1.34,
      p=0.017), C-reactive protein (HR 1.04, p<0.001), and statin use (HR 0.70,
      p=0.016). CONCLUSIONS: The incidence of non-CV death was high in patients with
      AHF, accounting for 30% of long-term mortality. Furthermore, the proportion of
      non-CV death increased in the later follow-up phase. Better understanding of non
      CV death and more comprehensive treatment of non-CV comorbidities are vital to
      further improving prognosis in AHF patients.

PMID- 29169754
TI  - Chronic lower-dose relaxin administration protects from arrhythmia in
      experimental myocardial infarction due to anti-inflammatory and anti-fibrotic
      properties.
AB  - BACKGROUND: The peptide hormone relaxin-2 (RLX) exerts beneficial effects during
      myocardial ischemia, but functional data on lower-dose RLX in myocardial
      infarction (MI) is lacking. Therefore, we investigated the impact of 75MUg/kg/d
      RLX treatment on electrical vulnerability and left ventricular function in a
      mouse model of MI. METHODS AND RESULTS: Standardized cryoinfarction of the left
      anterior ventricular wall was performed in mice. A two week treatment period with
      vehicle or RLX via subcutaneously implanted osmotic minipumps was started
      immediately after MI. The relaxin receptor RXFP1 was expressed on
      ventricular/atrial cardiomyocytes, myofibroblasts, macrophages and endothelial
      but not vascular smooth muscle cells of small coronary vessels. RLX treatment
      resulted in a significant reduction of ventricular tachycardia inducibility
      (vehicle: 91%, RLX: 18%, p<0.0001) and increased epicardial conduction velocity
      in the left ventricle and borderzone. Furthermore, left ventricular function
      following MI was improved in RLX treated mice (left ventricular ejection
      fraction; vehicle: 41.1+/-1.9%, RLX: 50.5+/-3.5%, p=0.04). Interestingly, scar
      formation was attenuated by RLX with decreased transcript expression of
      connective tissue growth factor. Transcript levels of the pro-inflammatory
      cytokines interleukin-6 and interleukin-1beta were upregulated in hearts of
      vehicle treated animals compared to mice without MI. Application of RLX
      attenuated this inflammatory response. In addition, macrophage infiltration was
      reduced in the borderzone of RLX treated mice. CONCLUSION: Treatment with lower
      dose RLX in mice prevents post-infarction ventricular tachycardia due to
      attenuation of scar formation and cardiac inflammation. Therefore, RLX could be
      evaluated as new therapeutic option in the treatment of MI.

PMID- 29169755
TI  - Vigorous exercise in hypertrophic cardiomyopathy: Benefits may outweigh the
      risks.

PMID- 29169756
TI  - Noncardiovascular death after acute heart failure. Do not lose the war while
      fighting for the failing heart.

PMID- 29169757
TI  - Hs-cTroponins for the prediction of recurrent cardiovascular events in patients
      with established CHD - A comparative analysis from the KAROLA study.
AB  - BACKGROUND: High-sensitivity Troponins (hs-cTnT and hs-cTnI) are established
      biomarkers to identify patients with an acute myocardial infarction. However,
      data comparing the capacity of these two subtypes in predicting recurrent
      cardiovascular disease (CVD) events in a population with stable coronary heart
      disease (CHD) after adjustment for several other modern biomarkers are lacking.
      METHODS: We measured both troponins at baseline in 1068 CHD patients, followed
      them for 13years, assessed a combined CVD endpoint, and adjusted for multiple
      traditional and novel risk factors. RESULTS: Both troponins correlated
      significantly with age, low and high BMI, male gender, statin therapy, and
      emerging biomarkers (e.g. cystatin C, NT-proBNP, GDF-15, hsCRP or galectin 3).
      During follow-up of 13years, 267 fatal and non-fatal CVD events occurred. Top
      quartiles of both troponin concentrations were significantly associated with CVD
      events compared to the bottom quartile after adjustment for age, gender and
      established CVD risk factors (hs-cTnT: hazard ratio (HR) 2.54 (95% CI, 1.60
      4.03), p for trend: <0.0001; hs-cTnI: HR 2.20 (95% CI, 1.44-3.36), p for trend:
      <0.0002 and 0.0003). However, after adjustment for other emerging biomarkers, the
      associations were no longer statistically significant (hs-cTnT: HR 1.63 (95% CI,
      0.97-2.73), p for trend: 0.17; hs-cTnI: HR 1.61 (95% CI, 1.00-2.60), p for trend:
      0.067). CONCLUSION: Both troponins are reliable biomarkers of recurrent
      cardiovascular events, especially if other novel, important markers such as NT
      proBNP, GDF-15 and galectin 3 are not available. Nevertheless, a further workup
      is still needed to explain the complex interaction of biomarkers indicating
      vascular and myocardial function.

PMID- 29169758
TI  - High sensitivity cardiac troponin T and I and risk stratification of patients
      with stable CHD: Is it time to incorporate this in routine clinical practice?

PMID- 29169759
TI  - Abnormal coronary vasoreactivity in transient left ventricular apical ballooning
      (tako-tsubo) syndrome.
AB  - BACKGROUND: The exact etiology and pathophysiologic mechanisms of tako-tsubo
      syndrome (TTS) remain controversial. OBJECTIVE: To further evaluate the abnormal
      coronary vasoreactivity and its possible anatomical substrate in TTS. METHODS: We
      studied 47 patients (46 women; age 67+/-12years) who underwent diagnostic cardiac
      catheterization and evaluation of coronary vasoreactivity by sequential
      acetylcholine (Ach), nitroglycerine and adenosine testing with angiographic and
      intracoronary pressure-Doppler flow monitoring. Coronary artery wall morphology
      was also evaluated by intravascular ultrasound (IVUS) imaging in 45 vessels of 43
      patients. RESULTS: Abnormal coronary vasoconstriction to Ach stimulation was
      elicited in 40 patients (85%) involving the LAD artery and its branches in 39
      (83%). Abnormal microvascular function was seen in 39 (83%) patients. Overall,
      hyperemic microvascular resistance index (HMR) was higher and Doppler coronary
      flow velocity reserve (CFVR) was lower in the LAD artery territory as compared to
      the reference territories (2.64+/-1.23 vs 2.05+/-0.56; p=0.008 and 1.95+/-0.7 vs
      2.3+/-0.6; p=0.018, respectively). IVUS revealed no plaque rupture, dissection or
      thrombosis but occult plaque formation and myocardial bridging were found as a
      possible anatomical substrate of endothelial dysfunction in 67% and 48.8%
      patients respectively. CONCLUSIONS: A global failure of coronary vasomotor
      function was demonstrated in most TTS patients. These findings implicate abnormal
      vasoconstrictive response to the activation of the sympathetic system as a
      potential mechanism involved in the pathogenesis of myocardial stunning in TTS.
      PERSPECTIVES: Competency in medical knowledge: Abnormal coronary vasoconstriction
      secondary to endothelial dysfunction may actively contribute to the clinical
      manifestation of acute coronary syndromes in patients with non-obstructive
      coronary disease. Translational outlook 1: TTS patients reveal a global failure
      of vasomotor function with both vasoconstrictive response to acetylcholine and
      increased hyperemic microvascular resistances in the territory of myocardial
      stunning. They may also show occult coronary atherosclerosis and myocardial
      bridging as the anatomic substrates of endothelial dysfunction. Translational
      outlook 2: The cardiac phenotype of TTS includes a high prevalence of coronary
      vasomotor disturbances. These findings implicate abnormal vasoconstrictive
      response to the activation of the sympathetic system as a potential mechanism
      involved in the pathogenesis of TTS in post-menopausal women. Thus, a systematic
      evaluation of coronary vasoreactivity could better characterize the syndrome.

PMID- 29169760
TI  - Coronary vasomotor dysfunction in apical ballooning (Takotsubo) syndrome: An
      innocent bystander or a prime suspect?

PMID- 29169761
TI  - The elusive link between sex hormone levels and Takotsubo syndrome.

PMID- 29169762
TI  - Low-dose of relaxin protects against arrhythmias and adverse left ventricle
      remodeling.

PMID- 29169763
TI  - Serum uric acid and acute coronary syndrome: Is there a role for functional
      markers of residual cardiovascular risk?

PMID- 29169766
TI  - Sweat mechanisms and dysfunctions in atopic dermatitis.
AB  - Skin barrier dysfunction is inherent to atopic dermatitis (AD), causing dryness,
      irritation, and increased permeability to irritants, allergens and pathogens.
      Eccrine sweat functions as part of the skin's protective barrier. Variations in
      sweat responses have been observed in patients with AD, and altered sweat
      composition and dynamics are under-recognized as important factors in the disease
      cycle. This review discusses the role that sweat plays in the pathogenesis of AD,
      examines evidence on abnormal sweat composition, secretion, and neuro-immune
      responses to sweat in atopic skin, and highlights the value of sweat management.

PMID- 29169765
TI  - Whole Exome Sequencing allows the identification of two novel groups of Xeroderma
      pigmentosum in Tunisia, XP-D and XP-E: Impact on molecular diagnosis.
AB  - BACKGROUND: Skin cancers (SC) are complex diseases that develop from complex
      combinations of genetic and environmental risk factors. One of the most severe
      and rare genetic diseases predisposing to SC is the Xeroderma pigmentosum (XP)
      syndrome. OBJECTIVES: First, to identify the genetic etiology of XP and to better
      classify affected patients. Second, to provide early molecular diagnosis for pre
      symptomatic patient and finally to offer genetic counseling for related
      individuals. METHODS: Whole Exome Sequencing (WES) and Run Of Homozygosity (ROH)
      were performed for two patients belonging to two different multiplex
      consanguineous families. The identified mutations were confirmed by Sanger
      sequencing and researched in ten Tunisian families including a total of 25
      affected individuals previously suspected as having XP group V (XP-V) form. All
      patients had mild dermatological manifestations, absence of neurological
      abnormalities and late onset of skin tumors. RESULTS: Screening for functional
      variations showed the presence of the ERCC2 p.Arg683Gln in XP14KA-2 patient and a
      novel mutation, DDB2 p. (Lys381Argfs*2), in XP51-MAH-1 patient. Sanger sequencing
      and familial segregation showed that the ERCC2 mutation is present at a
      homozygous state in 10 affected patients belonging to 3 families. The second
      mutation in DDB2, is present at a homozygous state in 5 affected cases belonging
      to the same family. These two mutations are absent in the remaining 10 affected
      patients. The ERCC2 c.2048G > A mutation is present in a medium ROH region (class
      B) suggesting that it mostly arises from ancient relatedness within individuals.
      However, the c.1138delG DDB2 mutation is present in a large ROH region (class C)
      suggesting that it arises from recent relatedness. CONCLUSION: To our knowledge,
      this is the first study that identifies XP-D and XP-E complementation groups in
      Tunisia. These two groups are very rare and under-diagnosed in the world and were
      not reported in North Africa.

PMID- 29169767
TI  - School Environment Is Related to Lower Health and Safety Risks Among Sexual
      Minority Middle and High School Students.
AB  - PURPOSE: The objective of this study was to examine the relationship between
      school involvement and connectedness with measures of sexual risk, substance use,
      and experience of violence among students who had sexual contact with the same
      sex or with both sexes. METHODS: A sample of middle school and high school
      students who participated in a study conducted in a large urban school district
      were selected based on their reported experience of having initiated sexual
      activity with same-sex partners. In classroom-based surveys, we assessed self
      reported involvement in school-based activities and feelings of school
      connectedness, as well as self-reported sexual risk, substance use, and
      experience of violence. RESULTS: Significant protective associations were found
      between school involvement and lifetime alcohol and marijuana use, and between
      school connectedness and ever having been in a fight, feeling safe at school, and
      drug use other than marijuana (all p < .05). CONCLUSIONS: Findings suggest that
      efforts to increase school involvement and connectedness provide a starting point
      for addressing significant health and safety concerns among students with same
      sex sexual activity.

PMID- 29169764
TI  - Female-specific survival advantage from transcatheter aortic valve implantation
      over surgical aortic valve replacement: Meta-analysis of the gender subgroups of
      randomised controlled trials including 3758 patients.
AB  - Transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) is
      the first area of interventional cardiology where women are treated as often as
      men. In this analysis of the gender specific results of randomised controlled
      trials (RCTs) comparing TAVI with surgical aortic valve replacement (SAVR) we
      aimed to determine whether gender affects the survival comparison between TAVI
      and SAVR. We identified all RCTs comparing TAVI versus SAVR for severe AS and
      reporting 1 and/or 2year survival. Summary odds ratios (ORs) were obtained using
      a random-effects model. Heterogeneity was assessed using the Q statistic and I2.
      Four RCTs met the criteria, totalling 3758 patients, 1706 women and 2052 men.
      Amongst females, TAVI recipients had a significantly lower mortality than SAVR
      recipients, at 1year (OR 0.68; 95%CI 0.50 to 0.94) and at 2years (OR 0.74; 95%CI
      0.58 to 0.95). Amongst males there was no difference in mortality between TAVI
      and SAVR, at 1year (OR 1.09; 95%CI 0.86 to 1.39) or 2years (OR 1.05; 95%CI 0.85
      to 1.3). The difference in treatment effect between genders was significant at
      both 1year (pinteraction=0.02) and 2years (pinteraction=0.04). In women TAVI has
      a 26 to 31% lower mortality odds than SAVR. In men, there is no difference in
      mortality between TAVI and SAVR.

PMID- 29169768
TI  - Increasing Patient Portal Usage: Preliminary Outcomes From the MyChart Genius
      Project.
AB  - PURPOSE: To determine the feasibility, acceptability, and preliminary
      effectiveness of dedicating staff ("MyChart Geniuses") to assist adolescents with
      patient portal sign-up; to examine patient satisfaction with MyChart Genius
      services; and to determine patient preferences for future communications related
      to health issues. METHODS: Adolescent patients (13-25 years old) in an urban,
      academic, primary care clinic were approached by MyChart Genius staff to assist
      with enrolling in MyChart and downloading the MyChart mobile App. Patients were
      also invited to partake in a brief, online survey assessing their technology use
      and access, as well as their preferences surrounding communication with their
      health-care providers. Survey responses were analyzed using SPSS Statistics (SPSS
      Inc., Chicago, IL). RESULTS: Ninety-six patients were approached, 84 (87.5%) of
      whom enrolled in MyChart. Sixty-four adolescents agreed to answer survey
      questions. Respondents were primarily African-American patients (87%), with a
      mean age of 18.7 years. The majority (79%) of participants were either satisfied
      or very satisfied with the Genius program. The respondents reported high access
      to and use of basic technology, and a high perceived need for an electronic
      health record App. Preferences for future communications with health-care
      providers revealed population subsets, indicating an area to further
      individualize interventions. CONCLUSIONS: This is one of the first studies to
      examine a strategy to increase patient portal uptake and usage among minority,
      urban adolescents (a group with demonstrated preferences on communications with
      health-care providers). The presence of specially trained MyChart Genius staff is
      a feasible, effective, and patient-satisfactory method of engaging with this
      group of adolescents.

PMID- 29169769
TI  - Online denoising of eye-blinks in electroencephalography.
AB  - OBJECTIVE: Due to its high temporal resolution, electroencephalography (EEG) has
      become a broadly-used technology for real-time brain monitoring applications such
      as neurofeedback (NFB) and brain-computer interfaces (BCI). However, since EEG
      signals are prone to artifacts, denoising is a crucial step that enables adequate
      subsequent data processing and interpretation. The aim of this study is to
      compare manual denoising to unsupervised online denoising, which is essential to
      real-time applications. METHODS: Denoising EEG for real-time applications
      requires the implementation of unsupervised and online methods. In order to
      permit genericity, these methods should not rely on electrooculography (EOG)
      traces nor on temporal/spatial templates of the artifacts. Two blind source
      separation (BSS) methods are analyzed in this paper with the aim of automatically
      correcting online eye-blink artifacts: the algorithm for multiple unknown signals
      extraction (AMUSE) and the approximate joint diagonalization of Fourier cospectra
      (AJDC). The chosen gold standard is a manual review of the EEG database carried
      out retrospectively by a human operator. Comparison is carried out using the
      spectral properties of the continuous EEG and event-related potentials (ERP).
      RESULTS AND CONCLUSION: The AJDC algorithm addresses limitations observed in
      AMUSE and outperforms it. No statistical difference is found between the manual
      and automatic approaches on a database composed of 15 healthy individuals, paving
      the way for an automated, operator-independent, and real-time eye-blink
      correction technique.

PMID- 29169770
TI  - Fatal serotonin syndrome in a patient with Marchiafava-Bignami disease: Combined
      neurological and psychiatric emergency.
AB  - Marchiafava-Bignami disease (MBD) is a rare fatal neurological disorder
      characterized by demyelination, primary degeneration, and necrosis of the corpus
      callosum. Although MBD is mostly associated with chronic alcohol consumption and
      malnutrition, it has been reported in non-alcoholic patients. Serotonin syndrome
      is a rare but potentially fatal side effect of antidepressants that results from
      overstimulation of both central and peripheral serotonergic receptors. In this
      report, we present a case with fatal serotonin syndrome happening in a non
      alcoholic patient with the chronic form of MBD. To our knowledge, this case is
      the first report of fatal serotonin syndrome due to citalopram in an MBD patient.
      The present report may indicate that citalopram and other SSRIs should not be
      used in patients with MBD. Our case is also among few reported cases in the
      literature where no cause was identified in a patient with no previous history of
      alcohol intake.

PMID- 29169771
TI  - Antiurolithiatic activity of natural constituents isolated from Aerva lanata.
AB  - BACKGROUND: Pashanabheda is used as antiurolithiatic in Ayurveda. In the present
      study, Aerva lanata (L) Juss. ex. Schult (Amaranthaceae) from Western Ghats of
      India was selected for isolation of active constituents and screening for
      antiurolithiatic potentials. OBJECTIVE: Screening of compounds isolated from A.
      lanata for antiurolithiatic potentials. MATERIALS AND METHODS: Ethylene glycol
      (0.75% v/v) induced urolithiasis model was used to study the antiurolithiatic
      activity in male Wistar albino rats. The animals were divided into five groups
      containing six each. Based on the LD50 of the plant extract (2000 mg/kg b.w)
      equivalent dose was calculated from their yield. Two isolated compounds
      (quercetin and betulin) of A. lanata were screened for antiurolithiatic
      potentials in calculi induced (ethylene glycol 0.75% v/v) male Wistar albino rats
      by administering 2 mg/kg b.w/day orally as test dose for 28 days. RESULTS: The
      urine volume was found to be significantly increased from 12.76 +/- 0.10 ml to
      21.35 +/- 0.20 ml in the rats treated by quercetin and 21.50 +/- 0.21 ml in rats
      treated by betulin. Urine microscopy revealed significant reduction (p < 0.001)
      in the size of calculi and significantly enhanced (p < 0.001) excretion of
      calcium, oxalate, phosphate, whereas the level of magnesium was increased. SEM of
      kidney sections has revealed reduction in the calculi in treated animals. Serum
      analysis has revealed significant reduction in the level of BUN and creatinine in
      treated rats. CONCLUSION: The isolated quercetin and betulin from A. lanata have
      shown mild diuretic effect as well as antiurolithiatic effect by significantly
      reducing the size of calculi in the kidneys and enhancing the excretion of
      calcium, phosphate, oxalate while maintaining the level of magnesium, which is
      reported to be one of the calculi inhibiting factors.

PMID- 29169772
TI  - Seasonal and pandemic influenza: global fatigue versus global preparedness.

PMID- 29169773
TI  - Reply to letter to the editor.

PMID- 29169774
TI  - Sir Denis Browne, the father of modern pediatric surgery.
AB  - Sir Denis John Wolko Browne (1892-1967), while not the first in the British Isles
      to devote his entire surgical practice to pediatric surgery, is accepted as "the
      father of pediatric surgery in the United Kingdom." He made contributions to
      operations as varied as tonsillectomy, pyloromyotomy, and hypospadias repair, and
      provided fundamental insights into the proper treatment of club foot, congenital
      dislocation of the hip, and cryptorchidism. He introduced the transverse
      laparotomy incision, primary repair of congenital intestinal obstruction, and the
      end-to-back anastomosis for intestinal atresia, techniques so commonly used that
      it is difficult to think of pediatric surgical operations done any differently.
      In addition, he invented the elegant Denis Browne retractor that remains in use
      today, one of the few eponymic instruments known by its originator's first and
      last name. He was among the founders of the British Association of Pediatric
      Surgeons, one of the first professional organizations in the field, and served as
      its first president. His legendary status was enhanced by an acerbic temperament
      that often surfaced in an outspoken and uncompromising advocacy on the behalf of
      the proper care of children. A larger-than-life figure in pediatric surgery,
      Browne's legacy is so wide-ranging and enduring that his unofficial title has
      been broadened to "the father of modern pediatric surgery."

PMID- 29169775
TI  - In and out of schizophrenia: Activation and deactivation of the negative and
      positive schemas.
AB  - Theorists, clinicians, and investigators have attempted to find a common source
      for the negative and positive symptoms of schizophrenia. We propose that a
      unified theory, based on a common cognitive structure not only has explanatory
      value, but can serve as a framework for a psychotherapeutic intervention.
      Specifically, we propose that the cognitive triad - the negative view of the
      self, others, and the future - is the source of the content for the negative and
      positive symptoms. We report literature supporting the relationship between each
      facet of the negative triad and each of the key symptoms: expressive negative
      symptoms, delusions, and verbal hallucinations. We conclude that the literature
      supports the validity of the cognitive model of negative and positive symptoms.
      The cognitive model furthers the understanding of the positive and negative
      symptoms of schizophrenia, and we describe how this provides a framework for a
      psychotherapeutic intervention.

PMID- 29169776
TI  - One-stage dynamic graciloplasty for anal incontinence.

PMID- 29169777
TI  - One-step FPLC-size-exclusion chromatography procedure for purification of rDMBT1
      6 kb with increased biological activity.
AB  - Deleted in Malignant Brain Tumor 1 (DMBT1, alias SAG or gp340) is a pattern
      recognition receptor involved in immune defense, cell polarization,
      differentiation and regeneration. To investigate the role of the protein in
      physiological and pathological processes, the protein has often been isolated
      from saliva or produced in vitro and purified by a multistep affinity
      purification procedure using bacteria, followed by FPLC. Here, we compared a
      simple, one-step FPLC-SEC protocol for purification of recombinant DMBT1 6 kb,
      with that of the standard bacteria affinity purification-based protocol. Our data
      suggest that our FPLC-SEC protocol yields DMBT1 in a more native conformation.

PMID- 29169778
TI  - 15N CEST data and traditional model-free analysis capture fast internal dynamics
      of DJ-1.
AB  - Previous studies have shown that relaxation parameters and fast protein dynamics
      can be quickly elucidated from 15N-CEST experiments [1]. Longitudinal R1 and
      transverse R2 values were reliably derived from fitting of CEST profiles. Herein
      we show that 15N-CEST experiments and traditional modelfree analysis provide the
      internal dynamics of three states of human protein DJ-1 at physiological
      temperature. The chemical exchange profiles show the absence of a minor state
      conformation and, in conjunction with 1H-15N NOEs, show increased mobility. R1
      and R2 values remained relatively unchanged at the three naturally occurring
      oxidation states of DJ-1, but exhibit striking NOE differences. The NOE data was,
      therefore, essential in determining the internal motions of the DJ-1 proteins. To
      the authors' knowledge, we present the first study that combines 15N CEST data
      with traditional model-free analyses in the study of a biological system and
      affirm that more 'lean' model-free approaches should be used cautiously.

PMID- 29169780
TI  - [Massive jejunal diverticulosis: Rare cause of intestinal malabsorption].

PMID- 29169779
TI  - Mind-Matter Interactions and the Frontal Lobes of the Brain: A Novel
      Neurobiological Model of Psi Inhibition.
AB  - CONTEXT: Despite a large literature on psi, which encompasses a range of
      experiences including putative telepathy (mind-mind connections), clairvoyance
      (perceiving distant objects or events), precognition (perceiving future events),
      and mind-matter interactions, there has been insufficient focus on the brain in
      relation to this controversial phenomenon. In contrast, our research is based on
      a novel neurobiological model suggesting that frontal brain systems act as a
      filter to inhibit psi and that the inhibitory mechanisms may relate to self
      awareness. OBJECTIVE: To identify frontal brain regions that may inhibit psi.
      DESIGN: We used mind-matter interactions to study psi in two participants with
      frontal lobe damage. The experimental task was to influence numerical output of a
      Random Event Generator translated into movement of an arrow on a computer screen
      to the right or left. Brain MRI was analyzed to determine frontal volume loss.
      RESULTS: The primary area of lesion overlap between the participants was in the
      left medial middle frontal region, an area related to self-awareness, and
      involved Brodmann areas 9, 10, and 32. Both participants showed a significant
      effect in moving the arrow to the right, i.e., contralateral to the side of
      primary lesion overlap. Effect sizes were much larger compared to normal
      participants. CONCLUSIONS: The medial frontal lobes may act as a biological
      filter to inhibit psi through mechanisms related to self-awareness.
      Neurobiological studies with a focus on the brain may open new avenues of
      research on psi and may significantly advance the state of this poorly understood
      field.

PMID- 29169781
TI  - Development of National Research and Clinical Agendas for Patient-Reported
      Outcomes in IR: Proceedings from a Multidisciplinary Consensus Panel.

PMID- 29169782
TI  - Radiation Segmentectomy versus Selective Chemoembolization in the Treatment of
      Early-Stage Hepatocellular Carcinoma.
AB  - PURPOSE: To compare outcomes of radiation segmentectomy (RS) and segmental
      transarterial chemoembolization in treatment of unresectable, solitary
      hepatocellular carcinoma (HCC) <= 3 cm. MATERIALS AND METHODS: From January 2012
      to January 2016, 534 and 877 patients were treated with radioembolization and
      transarterial chemoembolization, respectively. A cohort of 112 (radiation
      segmentectomy [RS], 55; chemoembolization, 57) locoregional therapy-naive
      patients with solitary HCC <= 3 cm without vascular invasion or metastasis was
      retrospectively identified and stratified according to baseline patient
      demographics, tumor characteristics, and laboratory values. Propensity score
      matching (PSM) was conducted using a nearest neighbor algorithm (1:1). Outcomes
      analyzed included laboratory toxicities, imaging response, time to secondary
      therapy (TTST), and overall survival. RESULTS: Before PSM, complete response (CR)
      rate was 81.2% for RS and 49.1% for chemoembolization (odds ratio 2.2; 95%
      confidence interval [CI], 1.4-3.3; P < .001). Median (95% CI) TTST after initial
      therapy was 246 days (135-250 d) in chemoembolization group and 700 days (308-812
      d) in RS group (hazard ratio 0.71; 95% CI, 0.55-0.92; P = .009). Overall survival
      before PSM was not significantly different between the 2 groups (P = .29).
      Overall CR rate after PSM was 92.1% in RS group and 52.6% in chemoembolization
      group (P = .005). Median (95% CI) TTST after matching was 161 days (76-350 d) in
      chemoembolization group and 812 days (363-812 d) in RS group (P = .001). Overall
      survival after matching was not significantly different between the 2 groups (P =
      .71). CONCLUSIONS: RS results in improved imaging response and longer TTST
      compared with transarterial chemoembolization in treatment of early-stage HCC.

PMID- 29169783
TI  - The 2017 Integrated IR Residency Match: Results of a National Survey of
      Applicants and Program Directors.
AB  - PURPOSE: To characterize and compare the experiences of matched applicants and
      program directors (PDs) participating in the first large-scale integrated
      interventional radiology (IR) residency match. MATERIALS AND METHODS: Survey
      questionnaires were distributed nationally to integrated IR applicants who
      matched in the 2017 Match cycle and PDs. Both groups were questioned regarding
      their experiences with the application, interview, rank, and match processes as
      well as applicant-specific and PD-specific information. Summary and descriptive
      statistics were applied to responses, and comparison of Likert scale responses
      was performed by two-sample t test. RESULTS: Sixty-one matched applicants (51.3%)
      and 34 PDs (55.7%) responded to the survey. Regarding the match process,
      applicants believed United States Medical Licensing Examination (USMLE) Step 1
      score (P = .002) and connection to a program's geographic location (P = .006)
      were significantly more important than PDs did, whereas PDs ranked grades (P =
      .049), class rank (P = .011), academic awards (P = .003), additional degrees (P <
      .001), and USMLE Step 2 Clinical Skills score (P < .001) as significantly more
      important factors than applicants did. Additional information regarding
      demographic data, medical school experiences in IR, application strategies,
      interview experiences, rank lists, the intern year, and match results are
      reported. CONCLUSIONS: The completion of the first large-scale integrated IR
      match represents a paradigm shift in the way in which IR practitioners are
      recruited and trained. This study provides valuable benchmark data and analysis
      that can be used to improve efforts to match the best-fitting applicants into the
      integrated IR residency and improve future match cycles for applicants and PDs
      alike.

PMID- 29169784
TI  - Fast-Track Registration: A Way to Increase Efficiency in the IR Division.
AB  - PURPOSE: To evaluate changes in patient registration process at an academic 2
      suite IR Division to determine if moving registration from the waiting room to
      the vascular holding area decreased amount of time patients spent in the
      Radiology Department and improved start times. MATERIALS AND METHODS: A data
      collection sheet was created by evaluating patient-related processes; event
      timestamps were recorded on the sheet. The control group consisted of 33 patients
      who registered using the traditional process. The fast-track group consisted of
      29 patients who bypassed the traditional registration procedure and were
      registered by nurses in the vascular holding area. RESULTS: Total time between
      control and fast-track groups significantly decreased from an average time of 215
      minutes to 178 minutes (P = .020). The average start time improved significantly
      from an average of 63 minutes after scheduled procedure start time for the
      control group to 33 minutes after the scheduled procedure start time for the fast
      track group (P = .009). Start time (P = .022), time spent in recovery area (P =
      .006), and total time, after correcting for differences in laboratory test
      turnaround time, (P = .010) decreased in variability after implementation of fast
      track registration. CONCLUSIONS: Implementing fast-track registration for
      outpatient subcutaneous port placement in the IR Division improved start times
      and decreased total time patients spent in the hospital, while also reducing
      variability in the process.

PMID- 29169785
TI  - [Parental alienation, child psychological abuse and DSM-5].
AB  - Psychiatric experts find it is easier to deal with more horrible crimes than
      highly conflictual divorces. In the former, projections are impossible and
      "files" raise very interesting issues with regard to criminology; in contrast, in
      the latter the expert is confronted not just with a family but also and lest one
      forget, a couple that at one point in time had loved each other. However, the
      separation resembles a bloodbath. We will not detail the various psychiatric
      pathologies, which may further complicate a separation: they are well-known and,
      on a procedural level, do not raise any specific concerns. We will however
      address "pathological divorces" where although individuals, assessed on a case-by
      case basis, are exempt from ascertainable or developing psychiatric pathologies,
      pathology permeates systemic relations, inextricably linked to hatred or disgust.
      In this light, fault-based divorces still remain rare: it is in this context,
      marked by defiance and doubt as to the parental competence of each member of the
      couple that the psychiatric expert intervenes, with a similar acknowledged
      mission to that of the court: recommendations to be offered regarding visitation
      and custody rights. Amongst the conflictual and inextricable situations the most
      often encountered in expert practice, the parental alienation syndrome (PAS) now
      known as parental alienation (PA) refers to all psychopathological manifestations
      observed in children subject to highly conflictual parental separations, and
      above all, the unjustified or inexplicable rejection of a parent by a child (or
      even by siblings). This recent entity has raised controversy: some even go so far
      as to deny the existence itself of this phenomenon claiming that it does not
      appear in the international classifications of psychiatric disorders.
      Consequently, it was not included in the last edition of the DSM and does not
      appear in the ICD classification of the OMS whose 11th edition is currently being
      prepared. The weaknesses in the scientific concept and its purely passionate
      dimension, including sexist controversies, must be carefully elucidated in the
      dismissal or denial of this pathology. The author raises various definitions of
      parental alienation of which the most recent is undoubtedly the least
      controversial. He discusses the reasons for the dismissal of the concept by the
      Scientific Committee of the DSM-5. This dismissal is however quite apparent as
      although the term "parental alienation" is not contained therein, we will show
      that the notion is clearly referred to in at least two chapters of the new
      American classification of mental disorders.

PMID- 29169786
TI  - Characterization of cellulolytic microbial consortium enriched on Napier grass
      using metagenomic approaches.
AB  - Energy grass is a promising substrate for production of biogas by anaerobic
      digestion. However, the conversion efficiency is limited by the enzymatically
      recalcitrant nature of cellulosic wastes. In this study, an active, structurally
      stable mesophilic lignocellulolytic degrading microbial consortium (Np-LMC) was
      constructed from forest compost soil microbiota by successive subcultivation on
      Napier grass under facultative anoxic conditions. According to tagged 16S rRNA
      gene amplicon sequencing, increasing abundance of facultative Proteobacteria was
      found in the middle of batch cycle which was then subsequently replaced by the
      cellulose degraders Firmicutes and Bacteroidetes along with decreasing CMCase,
      xylanase, and beta-glucanase activity profiles in the supernatant after 5 days of
      incubation. Anaerobic/facultative bacteria Dysgonomonas and Sedimentibacter and
      aerobic bacteria Comamonas were the major genera found in Np-LMC. The consortium
      was active on degradation of the native and delignified grass. Direct shotgun
      sequencing of the consortium metagenome revealed relatively high abundance of
      genes encoding for various lignocellulose degrading enzymes in 23 glycosyl
      hydrolase (GH) families compared to previously reported cellulolytic microbial
      communities in mammalian digestive tracts. Enzymes attacking cellulose and
      hemicellulose were dominated by GH2, 3, 5, 9, 10, 26, 28 and 43 in addition to a
      variety of carbohydrate esterases (CE) and auxiliary activities (AA), reflecting
      adaptation of the enzyme systems to the native herbaceous substrate. The
      consortium identified here represents the microcosm specifically bred on energy
      grass, with potential for enhancing degradation of fibrous substrates in
      bioenergy industry.

PMID- 29169787
TI  - Comprehensive, blinded assessment of balance in orthostatic tremor.
AB  - INTRODUCTION: Orthostatic Tremor (OT) is a movement disorder characterized by a
      sensation of unsteadiness and tremors in the 13-18 Hz range present upon
      standing. The pathophysiology of OT is not well understood but there is a
      relationship between the sensation of instability and leg tremors. Despite the
      sensation of unsteadiness, OT patients do not fall often and balance in OT has
      not been formally assessed. We present a prospective blinded study comparing
      balance assessment in patients with OT versus healthy controls. METHODS: We
      prospectively enrolled 34 surface Electromyography (EMG)-confirmed primary OT
      subjects and 21 healthy controls. Participants underwent evaluations of balance
      by blinded physical therapists (PT) with standardized, validated, commonly used
      balance scales and tasks. RESULTS: OT subjects were mostly female (30/34, 88%)
      and controls were majority males (13/20, 65%). The average age of OT subjects was
      68.5 years (range 54-87) and for controls was 69.4 (range 32-86). The average
      duration of OT symptoms was 18 years. OT subjects did significantly worse on all
      the balance scales and on most balance tasks including Berg Balance Scale,
      Functional Gait Assessment, Dynamic Gait Index, Unipedal Stance Test, Functional
      Reach Test and pull test. Gait speed and five times sit to stand were normal in
      OT. CONCLUSIONS: Common validated balance scales are significantly abnormal in
      primary OT. Despite the objective finding of impaired balance, OT patients do not
      commonly have falls. The reported sensation of unsteadiness in this patient
      population seems to be out of proportion to the number of actual falls. Further
      studies are needed to determine which components of commonly used balance scales
      are affected by a sensation of unsteadiness and fear of falling.

PMID- 29169788
TI  - Stellate ganglion block as rescue therapy in refractory vasospasm after
      subarachnoid hemorrhage.

PMID- 29169789
TI  - Assessment of right atrial pressure with two-dimensional, Doppler and speckle
      tracking echocardiography in patients with acute right ventricular myocardial
      infarction.

PMID- 29169790
TI  - ?

PMID- 29169791
TI  - In reply to "FastrachTM intubating laryngeal mask for traumatic cervical spinal
      cord injury".

PMID- 29169792
TI  - Systematic review and meta-analysis.
AB  - In this review the usual methods applied in systematic reviews and meta-analyses
      are outlined. The ideal hypothesis for a systematic review should be generated by
      information not used later in meta-analyses. The selection of studies involves
      searching in web repertories, and more than one should be consulted. A manual
      search in the references of articles, editorials, reviews, etc. is mandatory. The
      selection of studies should be made by two investigators on an independent basis.
      Data collection on quality of the selected reports is needed, applying validated
      scales and including specific questions on the main biases which could have a
      negative impact upon the research question. Such collection also should be
      carried out by two researchers on an independent basis. The most common
      procedures for combining studies with binary outcomes are described (inverse of
      variance, Mantel-Haenszel, and Peto), illustrating how they can be done using
      Stata commands. Assessment of heterogeneity and publication bias is also
      illustrated with the same program.

PMID- 29169793
TI  - Proteomic evaluation of human umbilical cord tissue exposed to polybrominated
      diphenyl ethers in an e-waste recycling area.
AB  - Parental exposure to polybrominated diphenyl ethers (PBDEs) is associated with
      adverse birth outcomes. This study aims to examine differentially-expressed
      protein profiles in umbilical cord tissue, derived from mothers exposed to PBDEs,
      and investigate candidate biomarkers to reveal the underlying molecular
      mechanisms. Umbilical cord samples were obtained from women residing in an
      electronic waste (e-waste) recycling area (Guiyu) and reference area (Haojiang)
      in China. The concentration of PBDEs in umbilical cord tissue was determined by
      gas chromatography and mass spectrometry (GC/MS). Isobaric tagging for relative
      and absolute quantification (iTRAQ)-based proteomic technology was conducted to
      analyze differentially-expressed protein profiles. The total PBDE concentration
      was approximately five-fold higher in umbilical cords from Guiyu than from
      Haojiang (median 71.92ng/g vs. 15.52ng/g lipid, P<0.01). Neonatal head
      circumference, body-mass index (BMI) and Apgar1 score were lower in Guiyu and
      negatively correlated with PBDE concentration (P<0.01). Proteomic analysis showed
      697 proteins were differentially expressed in the e-waste-exposed group compared
      with the reference group. The differentially-expressed proteins were principally
      involved in antioxidant defense, apoptosis, cell structure and metabolism. Among
      them, catalase and glutathione S-transferase omega-1, were down-regulated, and
      cytochrome c was found to be up-regulated, changes which were further verified by
      enzyme-linked immunosorbent assays. These results suggest that an antioxidant
      imbalance and cell apoptosis in the umbilical cord following PBDE exposure is
      associated with neonatal birth outcomes.

PMID- 29169794
TI  - FOCUS in Thoracic Surgery: Does Feasibility Mean Functionality?

PMID- 29169795
TI  - Paravertebral Block for Thoracic Surgery.
AB  - : Local anesthetic injected into a wedge-shaped space lateral to the spinal
      nerves as they emerge from the intervertebral foramina produces somatosensory and
      sympathetic nerve blockade effective for anesthesia and for managing pain of
      unilateral origin from the chest and abdomen. Paravertebral blockade (PVB) is
      versatile and may be applied unilaterally or bilaterally. Unlike thoracic
      epidural, the PVB technique may be used to avoid contralateral sympathectomy,
      thereby minimizing hypotension and leading to better preservation of blood
      pressure. There are no reports on systemic toxicity associated with bilateral PVB
      despite the need for relatively large doses of local anesthetics. This review
      includes an important historic background and captures the resurgence of PVB-an
      almost lost technique. Thoracic PVB provides post-thoracotomy pain relief
      comparable with thoracic epidural analgesia (TEA) with lower side effects
      supported by moderate-quality evidence. The feasibility and potential of
      bilateral thoracic PVB for bilateral thoracic surgery appear practical. However,
      there is existing controversy in the assumption that thoracic PVB is a
      satisfactory, safer alternative when anticoagulation status is a contraindication
      to thoracic epidural placement. During the last 2 decades of systematic reviews
      and meta-analyses, both TEA and PVB have been deemed appropriate in the
      management of thoracic surgery. A multimodal approach to analgesia includes
      regional techniques for thoracic surgery that may reduce the likelihood of the
      development of postoperative complications and chronic pain. PURPOSE OF THIS
      REVIEW: The authors evaluated current opinion, clinical practice, new multimodal
      adjuvants, regional anesthesia, and innovation and technology related PVB in the
      thoracic surgery patient population. The review focuses on history, techniques,
      application, ease of placement, and relative safety of this regional technique.
      For this review, studies and reference lists were retrieved from the Cochrane
      library, Embase, and Medline from January 1995 through January 2017. SUMMARY:
      Existing evidence demonstrates noninferiority of thoracic PVB compared with TEA
      for postoperative analgesia, with fewer side effects for unilateral and bilateral
      thoracic surgery, including video-assisted thoracoscopy. The determining factors
      in selecting the regional technique of choice include the following: (1)
      tolerance of side effects associated with TEA, (2) consensus on best practice or
      technique, and (3) operator experience. There is no consensus on the optimal
      approach for thoracic PVB technique or any standardization when comparing the
      landmark, ultrasound-guided, or stimulation-based PVB approaches. Moreover, the
      efficacy of TEA compared with PVB in preventing post-thoracotomy chronic pain
      syndrome has not been investigated thoroughly and requires future clinical
      trials.

PMID- 29169796
TI  - Physiological and Operative Severity Score for the enumeration of Mortality and
      Morbidity (POSSUM) System for Outcome Prediction in Elderly Patients Undergoing
      Major Vascular Surgery.
AB  - OBJECTIVE: POSSUM system is widely used and validated for 30-day mortality and
      morbidity prediction. The aim of this study was to evaluate the performance of
      five POSSUM's equations (POSSUM, P-POSSUM, V-POSSUM, V-POSSUM physiology and V
      POSSUM Cambridge) on predicting 30-day mortality and morbidity in elderly
      patients undergoing major elective vascular surgery. DESIGN: A retrospective
      longitudinal cohort study. SETTING: A study conducted at an University Hospital.
      PARTICIPANTS: 208 elderly patients (>= 60 years) undergoing major elective
      vascular surgery. MEASUREMENTS: Data collected from the clinical files included
      patient's characteristics, diagnosis, surgery, comorbidities, parameters from
      POSSUM score, 30, 60 and 90-day mortality and 30-day morbidity. POSSUM system's
      goodness-of-fit for predicting mortality and morbidity was assessed by Hosmer
      Lemeshow test (H-L T) and Standardized Mortality/Morbidity Ratio (SMR) and
      discriminative ability by the area under the ROC curves (ROC-AUC). Patients'
      average age was 70.8 years, 81% males. INTERVENTIONS: None. MAIN RESULTS: The
      overall 30-day mortality rate was 2.97% (n=6) and 30-day morbidity was 29.2%
      (n=59). POSSUM, P-POSSUM, V-POSSUM, V-POSSUM physiology and V-POSSUM Cambridge
      equation predicted an overall of 29.1, 4.43, 15.3, 21.9 and 13.5 deaths,
      respectively. POSSUM morbidity equation predicted 105.0 complications. H-LT p
      values were 0.001, 0.164, 0.208, 0.011, 0.331 and <0.001, respectively. SMRs and
      95% confidence interval (CI) were 0.21[0.04-0.37], 1.35[0.27-2.44], 0.39[0.08
      0.71], 0.27[0.06-0.49], 0.44[0.09-0.80] and 0.56[0.42-0.71], respectively. ROC
      AUC and 95% CI were 0.72[0.49-0.95], 0.72[0.49-0.95], 0.73[0.51-0.94], 0.69[0.50
      0.89], 0.72[0.52-0.92] and 0.71[0.63-0.79], respectively. CONCLUSIONS: P-POSSUM
      had the best performance predicting 30-day mortality. All the other overestimated
      30-day mortality. Prediction of morbidity was inadequate. POSSUM scoring models
      may not be robust tools for risk prediction in elderly patients undergoing major
      elective vascular surgery and need further calibration and discrimination.

PMID- 29169797
TI  - Carotid Artery Disease as a Predictor of In-Hospital Postoperative Stroke After
      Coronary Artery Bypass Grafting From 1999 to 2011.
AB  - BACKGROUND: In this study, the risk factors for stroke after coronary artery
      bypass grafting (CABG) were examined. In particular, the role of asymptomatic
      carotid artery stenosis (both unilateral and bilateral) as a predictor of in
      hospital postoperative stroke was investigated. Finally, the trends surrounding
      in-hospital postoperative stroke from 1999 to 2011 also were examined. The
      purpose of the study was to appropriately identify patients at high risk for
      stroke after CABG and spark discussion about the perioperative management of such
      patients. MATERIALS AND METHODS: Data from the Nationwide Inpatient Sample from
      1999 to 2011 were analyzed retrospectively. The study cohort was identified using
      the International Classification of Diseases, Ninth Revision, Clinical
      Modification and Projection Clinical Classification Software codes. Exploratory
      statistics, univariate analyses, and multivariable regression were used for this
      study. RESULTS: The analysis demonstrated that both asymptomatic unilateral and
      bilateral carotid stenoses were independent risk factors for in-hospital
      postoperative stroke. In addition, increasing age, female sex, increasing van
      Walraven score, paralysis, neurologic disorders, history of infective
      endocarditis, asymptomatic basilar stenosis, and cerebral occlusion all were
      demonstrated to be statistically significant predictors of stroke. Patients with
      carotid stenosis and a van Walraven score >14 were found to be particularly
      vulnerable to in-hospital postoperative stroke. Lastly, predictors of carotid
      stenosis were examined, and increasing age, female sex, and increasing van
      Walraven score all were found to be significant predictors of asymptomatic
      carotid stenosis. CONCLUSIONS: This study examined risk factors for stroke after
      CABG in a large, longitudinal, and population-based database. The study found
      that both unilateral and bilateral asymptomatic carotid stenoses are indeed risk
      factors for in-hospital postoperative stroke. In addition, a number of other
      predictors were identified. These results can be used to identify patients at
      high risk for perioperative stroke and hopefully decrease the rate of a
      devastating complication of CABG.

PMID- 29169798
TI  - Cardioplegia During Minimally Invasive Mitral Valve Surgery, a Team Approach.

PMID- 29169799
TI  - Pharmacokinetics of Magnesium Bolus Therapy in Cardiothoracic Surgery.
AB  - OBJECTIVE: To investigate the pharmacokinetics of a 20 mmol magnesium bolus in
      regards to serum and urinary magnesium concentration, volume of distribution, and
      half-life. DESIGN: Prospective, experimental study. SETTING: A university
      affiliated teaching hospital. PARTICIPANTS: Twenty consecutive cardiac surgery
      patients treated with magnesium bolus therapy for prevention of arrhythmia.
      INTERVENTIONS: A 20-mmol bolus of magnesium sulfate was administered
      intravenously. MEASUREMENTS AND MAIN RESULTS: Median magnesium levels increased
      from 1.04 (interquartile range 0.94-1.23) mmol/L to 1.72 (1.57-2.14) mmol/L after
      60 minutes of magnesium infusion (p < 0.001) but decreased to 1.27 (1.21-1.36)
      and 1.16 (1.11-1.21) mmol/L after 6 and 12 hours, respectively. Urinary magnesium
      concentration increased from 6.3 (4.2-14.5) mmol/L to 19.1 (7.4-34.5) mmol/L
      after 60 minutes (p < 0.001), followed by 22.7 (18.4-36.7) and 15 (8.4-19.7)
      mmol/L after 6 and 12 hours, respectively. Over the 12-hour observation period,
      the cumulative urinary magnesium excretion was 19.1 mmol (95.5% of the dose
      given). The median magnesium clearance was 10 (4.7-15.8) mL/min and increased to
      14.9 (3.8-20.7; p = 0.934) mL/min at 60 minutes. The estimated volume of
      distribution was 0.31 (0.28-0.34) L/kg. CONCLUSION: Magnesium bolus therapy after
      cardiac surgery leads to a significant but short-lived increase of magnesium
      serum concentration due to renal excretion and distribution, and the magnesium
      balance is neutral after 12 hours.

PMID- 29169800
TI  - TGF-beta1/Smad2/3/Foxp3 signaling is required for chronic stress-induced immune
      suppression.
AB  - Depending on the duration and severity, psychological tension and physical stress
      can enhance or suppress the immune system in both humans and animals. Although it
      has been established that chronic stress exerts a significant suppressive effect
      on immune function, the mechanisms by which affects immune responses remain
      elusive. By employing an in vivo murine system, we revealed that TGF
      beta1/Smad2/3/Foxp3 axis was remarkably activated following chronic stress.
      Furthermore, TLR9 and p38 MAPK played a critical role in the activation of TGF
      beta1/Smad2/3/Foxp3 signaling cascade. Moreover, inhibition of TGF
      beta1/Smad2/3/Foxp3 or p38 significantly attenuated chronic stress-induced
      lymphocyte apoptosis and apoptosis-related proteins, as well as the
      differentiation of T regulatory cells in spleen. Interestingly, disequilibrium of
      pro-inflammatory and anti-inflammatory cytokines balance caused by chronic stress
      was also rescued by blocking TGF-beta1/Smad2/3/Foxp3 axis. These findings yield
      insight into a novel mechanism by which chronic stress modulates immune functions
      and identifies new targets for the development of novel anti-immune suppressant
      medications.

PMID- 29169801
TI  - Evaluating melanocytic lesions with single nucleotide polymorphism (SNP)
      chromosomal microarray.
AB  - Histopathology is the gold standard for diagnosing melanocytic lesions; however,
      distinguishing benign versus malignant is not always clear histologically. Single
      nucleotide polymorphism (SNP) microarray analysis may help in making a definitive
      diagnosis. Here, we share our experience with the Oncoscan FFPE Assay and
      demonstrate its diagnostic utility in the context of ambiguous melanocytic
      lesions. Eleven archival melanocytic lesions, including three benign nevi, four
      melanomas, three BAP1-deficient Spitzoid nevi and one nevoid melanoma were
      selected for validation. SNP-array was performed according to the manufacturer's
      protocol, using the recommended 80ng of DNA; however, as little as 15ng was used
      if the extraction yield was lower. Concordance was assessed with H&E and various
      combinations of BAP1 and p16 immunohistochemical stains (IHC) and external
      reference laboratory chromosomal microarray results. After validation, the SNP
      array was utilized to make definitive diagnoses in four challenging cases.
      Oncoscan SNP array findings were in concordance with H&E, IHC, and reference
      laboratory chromosomal microarray testing. The SNP-based microarray can
      accurately detect copy number changes and aid in making a more definitive
      diagnosis of challenging melanocytic lesions. This can be accomplished using
      significantly less DNA than is required by other microarray technologies.

PMID- 29169802
TI  - AKT activity is elevated in aggressive thyroid neoplasms where it promotes
      proliferation and invasion.
AB  - The PI3K/AKT/mTOR signaling pathway controls major cellular processes such as
      cell growth, proliferation and survival. Stimulation of this pathway leads to AKT
      phosphorylation and activation, resulting in phosphorylation of mTOR and myriad
      other targets. AKT upregulation has been implicated in thyroid cancer
      pathogenesis and is a candidate treatment target for patients with advanced
      disease that has not responded to traditional therapies. Here we evaluate a large
      series of benign and malignant thyroid tumors for AKT activity and intracellular
      distribution. We also deplete AKT from multiple thyroid cancer cell lines,
      including putative cancer stem cell lines, and measure the effect on
      proliferation and invasion in vitro. We show that active AKT has a predominantly
      nuclear distribution and its expression is highest in anaplastic thyroid
      carcinomas and papillary thyroid carcinomas, including encapsulated and invasive
      follicular variants. Depletion of AKT in thyroid carcinoma cell lines led to
      greatly reduced proliferative capacity and resulted in a reduction of invasive
      potential. A reduction in invasion was also observed in the cancer stem cell
      compartment. Targeting AKT activity in the clinical setting may slow the growth
      and spread of aggressive thyroid neoplasms, and target the tumor stem cell
      compartment.

PMID- 29169803
TI  - Expression, purification and characterization of two leucine aminopeptidases of
      the blood fluke, Schistosoma mansoni.
AB  - Schistosomiasis is a major neglected tropical disease (NTD) and considered the
      most important of the human helminthiases in terms of morbidity and mortality.
      Whereas treatment with praziquantel has been effective since the 1980s, the
      potential for the emergence of drug resistance has propelled the search for new
      interventions. Studies have revealed key roles of proteases in parasitic
      helminths during establishment of infection, tissue invasion, immune evasion,
      parasite feeding and development throughout the different developmental stages,
      pinpointing them as possible candidates. The leucine aminopeptidases (LAPs),
      members of the M17 family of Zn-metalloproteases, preferentially cleave leucine
      (Leu) residues at the N-terminal end of proteins and short peptides. These
      enzymes display broad proteolytic activities beyond Leu hydrolysis and are
      involved in processing, maturation, activation and/or degradation of substrates.
      As a vaccine immunogen, LAP induces protection against infection with the liver
      fluke Fasciola hepatica. Herein, two LAPs, SmLAP1 (Smp_030000) and SmLAP2
      (Smp_083870) of the human blood fluke Schistosoma mansoni were cloned, expressed,
      purified and biochemically characterized. The enzymes differed in activity
      against diagnostic substrates, including leucine, methionine and arginine, with
      an optimal pH of 8.0. The activity increased in the presence of Mg+2 and Mn+2,
      and was inhibited by bestatin, a specific inhibitor of aminopeptidase. In
      addition, 1,10-phenanthroline and EDTA inhibited the enzymatic activity of
      SmLAP2. Finally, immunolocalization using antibodies specific for SmLAP1 and
      SmLAP2 identified the expression of these proteases in the egg and adult
      developmental stages of S. mansoni, and in intestinal epithelia, vitelline cells
      and sub-tegumental regions of the parasite. Characterization of schistosome
      proteases not only enhances understanding of the biology of schistosomes and
      schistosomiasis, but may also provide novel intervention approaches.

PMID- 29169804
TI  - Agraphia manifesting during a WhatsApp conversation.

PMID- 29169805
TI  - Evaluation of the duration of the effect of botulinum toxin in clinical practice.

PMID- 29169806
TI  - Expanding FOXG1 syndrome phenotype.

PMID- 29169807
TI  - Subacute central pontine myelinolysis secondary to hyperglycaemia.

PMID- 29169808
TI  - Anti-Hu associated paraneoplastic neuropathy simulating an axonal variant of
      Guillain-Barre syndrome.

PMID- 29169809
TI  - Carotid pseudo-occlusion: A concept to consider in acute stroke.

PMID- 29169810
TI  - Evidence and experience with onabotulinumtoxinA in chronic migraine:
      Recommendations for daily clinical practice.
AB  - OnabotulinumtoxinA has been demonstrated to be effective as a preventive
      treatment in patients with chronic migraine (CM). Five years after the approval
      of onabotulinumtoxinA in Spain, the Headache Study Group of the Spanish Society
      of Neurology considered it worthwhile to gather a group of experts in treating
      patients with CM in order to draw up, based on current evidence and our own
      experience, a series of guidelines aimed at facilitating the use of the drug in
      daily clinical practice. For this purpose, we posed 12 questions that we ask
      ourselves as doctors, and which we are also asked by our patients. Each author
      responded to one question, and the document was then reviewed by everyone. We
      hope that this review will constitute a practical tool to help neurologists
      treating patients with CM.

PMID- 29169811
TI  - Evidence of and experience with the use of onabotulinumtoxinA in trigeminal
      neuralgia and primary headaches other than chronic migraine.
AB  - INTRODUCTION: In the field of headaches, onabotulinumtoxinA (onabotA) is well
      established as a treatment for chronic migraine (CM). In recent years, it has
      been used increasingly to treat other primary headaches (high-frequency episodic
      migraine, trigeminal-autonomic cephalalgias, nummular headache) and trigeminal
      neuralgia. As this treatment will progressively be incorporated in the management
      of these patients, we consider it necessary to reflect, with a fundamentally
      practical approach, on the possible indications of onabotA, beyond CM, as well as
      its administration protocol, which will differ according to the type of headache
      and/or neuralgia. DEVELOPMENT: This consensus document was drafted based on a
      thorough review and analysis of the existing literature and our own clinical
      experience. The aim of the document is to serve as guidelines for professionals
      administering onabotA treatment. The first part will address onabotA's mechanism
      of action, and reasons for its use in other types of headache, from a
      physiopathological and clinical perspective. In the second part, we will review
      the available evidence and studies published in recent years. We will add an
      "expert recommendation" based on our own clinical experience, showing the best
      patient profile for this treatment and the most adequate dose and administration
      protocol. CONCLUSION: Treatment with onabotA should always be individualised and
      considered in selected patients who have not responded to conventional therapy.

PMID- 29169812
TI  - Epilepsy in Africa: Past, present, and future.

PMID- 29169814
TI  - Safety of repeated sessions of transcranial direct current stimulation: A
      systematic review.
AB  - BACKGROUND: Repeated sessions of transcranial direct current stimulation (tDCS)
      are increasingly used for therapeutic applications. However, adverse events (AEs)
      associated with repeated sessions have not been comprehensively evaluated.
      OBJECTIVE: The aim of this study was therefore to evaluate the safety of repeated
      sessions of tDCS, examining AE risk relative to tDCS exposure. Further, to
      identify whether certain participant populations are particularly at risk from
      tDCS. METHODS: A systematic review and meta-analysis included sham-controlled
      studies (up to June 2017) involving two or more tDCS sessions, spaced not more
      than a day apart. Data was extracted on AEs reported, total tDCS exposure
      (cumulative charge), and diagnostic groups (Healthy, Pain Disorder, Stroke,
      Neurocognitive Disorder, Neuropsychiatric Disorder, and Other). Univariate simple
      linear meta-regression analyses examined AE likelihood, comparing active and sham
      tDCS, with increasing exposure. Rates of AEs were compared for diagnostic groups.
      RESULTS: 158 studies (total 4130 participants) met inclusion criteria and were
      included for quantitative analyses. The incidence of AEs (examined per session,
      by proportion of participants, and by the number of studies reporting AEs) did
      not increase with higher levels of tDCS exposure. Furthermore, AE rates were not
      found to be greater for any diagnostic group. CONCLUSIONS: Little evidence was
      found to suggest that repeated sessions of active tDCS pose increased risk to
      participants compared to sham tDCS within the limits of parameters used to date.
      Increased risks associated with greater levels of exposure to tDCS, or rare and
      under-reported AEs, however, cannot be ruled out.

PMID- 29169813
TI  - [Clinical problems in medical mycology: Problem number 51].
AB  - A 48 year-old immunocompetent woman, who had a nodular lesion in the neck and a
      dense infiltrate at the lower lobe of the left lung, presented at the Mycology
      Unit of Muniz Hospital of Buenos Aires City. The pulmonary infiltrate disappeared
      spontaneously 3 months later. The histopathological study of the nodular lesion
      showed capsulated yeasts (mucicarmin and alcian blue positive stains) compatible
      with Cryptococcus. The mycological study of a new sample, obtained by a nodular
      puncture, allowed the isolation of yeasts, identified as Cryptococcus gattii
      (VGII). Latex test for Cryptococcus capsular antigen in serum was positive
      (1/100). CSF cultures rendered negative results. Fluconazole at a daily dose of
      800mg was given during 45 days with partial improvement; as cultures from a new
      clinical sample were positive for Cryptococcus, the antimycotic was changed to
      itraconazole 400mg/day for 5 months, with an excellent clinical response.

PMID- 29169817
TI  - The French Infectious Diseases Society's readiness and response to epidemic or
      biological risk-the current situation following the Middle East respiratory
      syndrome coronavirus and Ebola virus disease alerts.
AB  - CONTEXT: In 2012, the French Infectious Diseases Society (French acronym SPILF)
      initiated the "Coordination of epidemic and biological risk" (SPILF-COREB -
      Emergences [SCE]) group to support the readiness and response of healthcare
      workers (HCWs) to new alerts. OBJECTIVE: To present the SCE group, its
      functioning, and the main support it provided for frontline HCWs. METHODS: A
      multidisciplinary group of heads of infectious disease departments from reference
      hospitals was created to build a network of clinical expertise for care,
      training, and research in the field of epidemic and biological risk (EBR). The
      network developed a set of standardized operational procedures (SOPs) to guide
      interventions to manage EBR-suspect patients. RESULTS: A working group created
      the SOP aimed at frontline HCWs taking care of patients. Priority was given to
      the development of a generic procedure, which was then adapted according to the
      current alert. Five key steps were identified and hierarchized: detecting,
      protecting, caring for, alerting, and referring the EBR patient. The interaction
      between clinicians and those responsible for the protection of the community was
      crucial. The SOPs validated by the SPILF and its affiliates were disseminated to
      a wide range of key stakeholders through various media including workshops and
      the SPILF's website. CONCLUSION: SPILF can easily adapt and timely mobilize the
      EBR expertise in case of an alert. The present work suggests that sharing and
      discussing this experience, initiated at the European level, can generate a new
      collective expertise and needs to be further developed and strengthened.

PMID- 29169816
TI  - Existing and investigational therapies for the treatment of Clostridium difficile
      infection: A focus on narrow spectrum, microbiota-sparing agents.
AB  - Despite intense international attention and efforts to reduce its incidence,
      Clostridium difficile infection (CDI) remains a significant concern for patients,
      clinicians, and healthcare organizations. It is costly for payers and disabling
      for patients. Furthermore, recurrent CDI is particularly difficult to manage,
      resulting in excess mortality, hospital length of stay, and other healthcare
      resource use. A greater understanding of the role of the gut microbiome has
      emphasized the importance of this diverse community in providing colonization
      resistance against CDI. The introduction of fidaxomicin, which has limited effect
      on the microflora has improved clinical outcomes in relation to disease
      recurrence. There are a number of other new agents in development, which appear
      to have a narrow spectrum of activity whilst exerting minimal effect on the
      microflora. Whilst the role of these emerging agents in the treatment of CDI is
      presently unclear, they appear to be promising candidates.

PMID- 29169815
TI  - Orchestration of epithelial-derived cytokines and innate immune cells in allergic
      airway inflammation.
AB  - Allergic asthma, a chronic respiratory disease, is a leading worldwide health
      problem, which inflames and constricts the airways, leading to breathing
      difficulty. Many studies have focused on the pathogenesis contributed by the
      adaptive immune system, including CD4+ T lymphocytes in delayed type
      hypersensitivity and B cell-produced IgE in anaphylaxis. More recently, a focus
      on the airway mucosal barrier and the innate immune system has highlighted, in
      coordination with T and B cells, to initiate and establish disease. This review
      highlights the impacts of epithelial-derived cytokines and innate immune cells on
      allergic airway reactions.

PMID- 29169818
TI  - Introduction of a Horizontal and Vertical Split Flow Model of Emergency
      Department Patients as a Response to Overcrowding.
AB  - INTRODUCTION: ED overcrowding is an issue that is affecting every emergency
      department and every hospital. The inability to maintain patient flow into and
      out of the emergency department paralyzes the ability to provide effective and
      timely patient care. Many solutions have been proposed on how to mitigate the
      effects of ED overcrowding. Solutions involve either hospital-wide initiatives or
      ED-based solutions. In this article, the authors seek to describe and provide
      metrics for a patient flow methodology that targets ESI 3 patients in a vertical
      flow model. METHODS: In the Stanford Emergency Department, a vertical flow model
      was created from existing ED space by removing fold-down horizontal stretchers
      and replacing them with multiple chairs that allowed for assessment and medical
      management in an upright sitting position. The model was launched and sustained
      through frequent interdisciplinary huddles, detailed inclusion and exclusion
      criteria, scripted text on how to promote the flow model to patients, and close
      analytics of metrics. Metrics for success included patient length of stay (LOS)
      for those triaged to the vertical flow area compared with ESI 3 patients triaged
      to the traditional emergency department as a comparison group. The secondary
      outcome is the total number of patients seen in the vertical flow area. This was
      a 6-month-September 2014, to February 2015-retrospective pre- and
      postintervention study that examined LOS as a marker for effective launch and
      implementation of a vertical patient workflow model. RESULTS: The patients
      triaged to the vertical flow area in the study period tended to be younger than
      in the control period (43 years versus 52 years, P = 0.00). There was a
      significant decrease in our primary end point: the total LOS for ESI 3 patients
      triaged to the vertical flow area (270 minutes versus 384 minutes, P = 0.00).
      CONCLUSION: Implementation of a vertical patient flow strategy can decrease LOS
      for the vertical ESI 3 patients based upon the inclusion and exclusion criteria.
      Furthermore, this is accomplished with minimal financial investment within the
      physical constraints of an existing emergency department.

PMID- 29169819
TI  - Use of Capnography to Optimize Procedural Sedation in the Emergency Department
      Pediatric Population.

PMID- 29169820
TI  - Robotic and hybrid robotic transversus abdominis release may be performed with
      low length of stay and wound morbidity.
AB  - The objective of our study was to compare length of stay and wound complications
      after hybrid robotic transversus abdominis release (hrTAR) vs. robotic
      transversus abdominis release (rTAR) Two cohorts of patients undergoing robotic
      (rTAR) and hybrid robotic (hrTAR) performed by two surgeons at a single
      institution were analyzed. Mean length of stay (LOS) and incidence of surgical
      site occurrences (SSO) were compared. 57 patients undergoing rTAR and 25 patients
      undergoing hrTAR were analyzed. The hrTAR group had larger mean hernia dimensions
      and a larger proportion of men but otherwise the patient cohorts were similar.
      LOS was not statistically different between rTAR and hrTAR (2.8 vs 3.7 days p =
      0.06). We found no difference in incidence of surgical site occurrences between
      the two groups (7.0% vs 4.0% p = 0.52). Hybrid robotic assisted TAR allows for
      repair of complex ventral hernias with similar lengths of stay and wound
      morbidity to pure robotic repairs.

PMID- 29169821
TI  - Faculty perceptions of resident skills decay during dedicated research
      fellowships.
AB  - BACKGROUND: Residents engaging in dedicated research experiences may return to
      clinical training with less surgical skill. The study aims were 1) to evaluate
      faculty perceptions of residents skills decay during dedicated research
      fellowships, and 2) to compare faculty and resident perceptions of residents
      skills decay. METHODS: Faculty and residents were surveyed on resident research
      practices and perceptions of resident skills decay. RESULTS: Faculty thought
      residents returning from research demonstrate less technical skill (Median = 4; 5
      point Likert scale, 1 = Strongly disagree, 5 = Strongly agree), demonstrate less
      confidence (Median = 4), and require more instruction (Median = 4). Both faculty
      and residents perceived the largest skill reduction in complex procedures,
      technical surgical skills, and knowledge of procedure steps (p < 0.05).
      CONCLUSION: While dedicated research experiences provide valuable academic
      experience, there is a cost to clinical skills retention and confidence
      specifically in the areas of complex operative procedures and technical surgical
      skills.

PMID- 29169822
TI  - Faculty feedback versus residents' self-assessment of operative performance:
      Different but complementary.
AB  - BACKGROUND: Surgical training requires development of both technical and
      cognitive skills. The study analyzed feedback by faculty and residents' self
      assessments during a laparoscopic training course to identify structure of
      feedback in this context and compared the focus of trainees to faculty. METHODS:
      This study collected assessments by surgical residents and faculty during an
      intensive laparoscopic training course at a single institution. The residents'
      operative performance was assessed using validated assessment tools including
      free text feedback. Assessments were completed immediately following procedures.
      Feedback was analyzed using qualitative method. RESULTS: Eighty (80) residents
      participated. Three themes were identified: Assessment, instruction and occasion.
      Faculty provided significantly more feedback than trainees. Moreover, the content
      of feedback was different. Residents focused on technical performance, while
      faculty commented on technical and cognitive skills, efficiency and level of
      independence. Errors were mainly addressed by faculty. CONCLUSION: This study
      demonstrated differences in cognitive focus of trainees and faculty. Text
      feedback is informative in understanding perceived challenges. Faculty provided
      explicit assessment and instruction for improvement. The effectiveness of self
      assessment and feedback should be further studied.

PMID- 29169823
TI  - Effect of intra-operative single dose of dexamethasone for control of post
      operative nausea and vomiting on the control of glucose levels in diabetic
      patients.
AB  - BACKGROUND: Dexamethasone adds a unique challenge to glycemic control, and it may
      complicate patient care if there is an association between intra-operative
      dexamethasone and blood glucose levels. METHODS: We analyzed 396 diabetic
      patients who underwent general anesthesia for various surgical procedures and
      were hospitalized post-operatively for at least 24 h between January 2015 and
      June 2016. Patients were classified into two groups-those who received
      dexamethasone intra-operatively and those who did not. The groups were analyzed
      for blood glucose changes during and following their procedure. RESULTS: A total
      of 396 diabetic patients (152 (38.8%) dexamethasone group; 244 (62.2%) control)
      were included. The dexamethasone group had significantly lower preoperative blood
      glucose (135.5 mmol/L) compared to the control group (144.4 mmol/L) (p = 0.04)
      and significantly lower proportion of patients who had received insulin during
      surgery (14.9%) compared to the control group (23.4%) (p = 0.04). Overall,
      glucose levels declined from pre-op to post-op day 1 by 9.6 (62.9) (p = 0.007).
      CONCLUSION: Diabetic patients receiving dexamethasone for control of post
      operative nausea during surgery are at greater risk for increasing blood glucose
      levels and difficult glycemic control during and after surgery compared to
      patients receiving other medications to control post-operative nausea.

PMID- 29169824
TI  - Implementation of a flipped classroom approach to promote active learning in the
      third-year surgery clerkship.
AB  - BACKGROUND: Constructivist student-centered instructional models such as the
      flipped classroom (FC) have been shown to improve learning. METHODS: A FC
      approach was implemented for the surgery clerkship. Data was collected in phase 1
      to evaluate student learning and attitudes. Based on these results, questions for
      the phase 2 open-ended survey were developed to improve understanding of learner
      attitudes, and ascertain how well the FC aligns with constructivist principles.
      RESULTS: There was no significant difference in shelf exam performance between
      the control and intervention groups. A majority of students agreed that they
      preferred the FC over lectures, and that their learning improved. Open-ended
      survey analysis demonstrated that the FC fostered self-directed, active learning,
      and that the in-class sessions facilitated application of concepts and deeper
      learning. Areas identified for improvement included better alignment with
      learning preferences through greater variety of pre-class learning options,
      improvement of podcast technical quality, and utilization of smaller in-class
      discussion groups. CONCLUSIONS: Students had a positive perception of the FC. The
      FC supports self-directed and more active and deeper in-class learning.

PMID- 29169825
TI  - Nitric oxide-cGMP-PKG signaling in the bed nucleus of the stria terminalis
      modulates the cardiovascular responses to stress in male rats.
AB  - The bed nucleus of the stria terminalis (BNST) constitutes an important component
      of neural substrates of physiological and behavioral responses to aversive
      stimuli, and it has been implicated on cardiovascular responses evoked by stress.
      Nevertheless, the local neurochemical mechanisms involved in BNST control of
      cardiovascular responses during aversive threats are still poorly understood.
      Thus, the aim of the present study was to assess the involvement of activation in
      the BNST of the neuronal isoform of the enzyme nitric oxide synthase (nNOS), as
      well as of signaling mechanisms related to nitric oxide effects such as soluble
      guanylate cyclase (sGC) and protein kinase G (PKG) on cardiovascular responses
      induced by an acute session of restraint stress in male rats. We observed that
      bilateral microinjection of either the nonselective NOS inhibitor Nomega-Nitro-L
      arginine methyl ester (L-NAME), the selective nNOS inhibitor Nomega-Propyl-L
      arginine (NPLA) or the sGC inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one
      (ODQ) into the BNST enhanced the tachycardic response and decreased the drop in
      tail cutaneous temperature evoked by acute restraint stress, but without
      affecting the increase on blood pressure. Bilateral BNST treatment with the
      selective PKG inhibitor KT5823 also facilitated the heart rate increase and
      decreased the drop in cutaneous temperature, in addition to enhancing the blood
      pressure increase. Taken together, these results provide evidence that NO
      released from nNOS and activation of sGC and PKG within the BNST play an
      inhibitory influence on tachycardia to stress, whereas this signaling mechanism
      mediates the sympathetic-mediated cutaneous vasoconstriction.

PMID- 29169827
TI  - In response to: Re-evaluating the effect of age on physical activity over the
      lifespan.

PMID- 29169826
TI  - Striatal structure and its association with N-Acetylaspartate and glutamate in
      autism spectrum disorder and obsessive compulsive disorder.
AB  - Autism spectrum disorders (ASD) and obsessive compulsive disorder (OCD) are often
      comorbid and are associated with changes in striatal volumes and N
      Acetylaspartate (NAA) and glutamate levels. Here, we investigated the relation
      between dorsal striatal volume and NAA and glutamate levels. We additionally
      compared striatal volume and shape between ASD, OCD and controls. T1-weighted
      magnetic resonance (MR) images, proton spectra (1H-MRS) in the left striatum, and
      phenotypic information were collected from 54 children with ASD, 32 with OCD, and
      56 controls (aged 8-13 years) in a four-site study. Dorsal striatal volume and
      shape were determined using the FMRIB integrated registration and segmentation
      tool (FIRST). Spectra were processed with Linear Combination Model. The
      relationship of left striatal volume with NAA and glutamate was investigated, and
      group comparisons were performed for NAA levels and for bilateral striatal volume
      and shape. NAA levels were lower in subjects with ASD compared with controls
      (t=2.86, p=0.005) and were associated with striatal volume (beta=0.37, t=2.78,
      p=0.008). Glutamate levels were also associated with volume in the ASD group
      (beta=0.38, t=2.46, p=0.018). No group differences were found for striatal volume
      or shape, but a post-hoc diagnosis-by-hemisphere interaction (F(2,129)=3.86,
      p=0.024) revealed greater asymmetry (right>left) in striatal volume for the
      disorder-groups compared with controls. Our findings show involvement of NAA and
      glutamate in striatal volume in ASD and suggest greater asymmetry in paediatric
      ASD and OCD compared with controls, pointing to overlapping subcortical
      abnormalities. The lower NAA in ASD reflects reduced neuronal integrity or
      impaired neuronal functioning.

PMID- 29169828
TI  - Comment on: concurrent bariatric surgery and paraesophageal hernia repair:
      comparison of sleeve gastrectomy and Roux-en-Y gastric bypass.

PMID- 29169829
TI  - Paired editorial: bariatric patients' reported motivations for surgery and their
      relationship to weight status and health.

PMID- 29169830
TI  - Rapamycin enhances lytic replication of Epstein-Barr virus in gastric carcinoma
      cells by increasing the transcriptional activities of immediate-early lytic
      promoters.
AB  - Epstein-Barr virus (EBV), a human herpesvirus, is linked to both epithelial and
      lymphoid malignancies. Induction of EBV reactivation is a potential therapeutic
      strategy for EBV-associated tumors. In this study, we assessed the effects of
      rapamycin on EBV reactivation in gastric carcinoma cells. We found that rapamycin
      upregulated expression of EBV lytic proteins and increased the viral
      proliferation triggered by the EBV lytic inducer sodium butyrate. Reverse
      transcription-qPCR, luciferase activity assays, chromatin immunoprecipitation and
      western blotting were employed to explore the mechanism by which rapamycin
      promotes EBV reactivation. Our results showed that rapamycin treatment resulted
      in increased mRNA levels of EBV immediate-early genes. Rapamycin also enhanced
      the transcriptional activities of the EBV immediate-early lytic promoters Zp and
      Rp by strengthening Sp1 binding. Repression of the cellular ataxia telangiectasia
      mutated/p53 pathway by siRNA-mediated knockdown of the ataxia telangiectasia
      mutated gene significantly abrogated virus reactivation by rapamycin/sodium
      butyrate treatment, indicating that the ataxia telangiectasia-mutated/p53 pathway
      is involved in rapamycin-promoted EBV reactivation. Taken together, these
      findings demonstrate that rapamycin might have the potential to enhance the
      effectiveness of oncolytic viral therapies developed for EBV-associated
      malignancies.

PMID- 29169832
TI  - A novel insect-infecting virga/nege-like virus group and its pervasive
      endogenization into insect genomes.
AB  - Insects are the host and vector of diverse viruses including those that infect
      vertebrates, plants, and fungi. Recent wide-scale transcriptomic analyses have
      uncovered the existence of a number of novel insect viruses belonging to an
      alphavirus-like superfamily (virgavirus/negevirus-related lineage). In this
      study, through an in silico search using publicly available insect transcriptomic
      data, we found numerous virus-like sequences related to insect virga/nege-like
      viruses. Phylogenetic analysis showed that these novel viruses and related virus
      like sequences fill the major phylogenetic gaps between insect and plant
      virga/negevirus lineages. Interestingly, one of the phylogenetic clades
      represents a unique insect-infecting virus group. Its members encode putative
      coat proteins which contained a conserved domain similar to that usually found in
      the coat protein of plant viruses in the family Virgaviridae. Furthermore, we
      discovered endogenous viral elements (EVEs) related to virga/nege-like viruses in
      the insect genomes, which enhances our understanding on their evolution. Database
      searches using the sequence of one member from this group revealed the presence
      of EVEs in a wide range of insect species, suggesting that there has been
      prevalent infection by this virus group since ancient times. Besides, we present
      detailed EVE integration profiles of this virus group in some species of the
      Bombus genus of bee families. A large variation in EVE patterns among Bombus
      species suggested that while some integration events occurred after the species
      divergence, others occurred before it. Our analyses support the view that insect
      and plant virga/nege-related viruses might share common virus origin(s).

PMID- 29169831
TI  - Next generation sequencing elucidates cacao badnavirus diversity and reveals the
      existence of more than ten viral species.
AB  - Cacao swollen shoot virus is a member of the family Caulimoviridae, genus
      Badnavirus and is naturally transmitted to Theobroma cacao (L.) by several
      mealybug species. CSSV populations in West African countries are highly variable
      and genetically structured into several different groups based on the diversity
      in the first part of ORF3 which encodes the movement protein. To unravel the
      extent of isolate diversity and address the problems of low titer and mixed viral
      sequences in samples, we used Illumina MiSeq and HiSeq technology. We were able
      to reconstruct de novo 20 new complete genomes from cacao samples collected in
      the Cocoa Research Institute of Ghana (CRIG) Museum and from the field samples
      collected in Cote d'Ivoire or Ghana. Based on the 20% threshold of nucleotide
      divergence in the reverse transcriptase/ribonuclease H (RT/RNase H) region which
      denotes species demarcation, we conclude there exist seven new species associated
      with the cacao swollen shoot disease. These new species along with the three
      already described leads to ten, the total number of the complex of viral species
      associated with the disease. A sample from Sri Lanka exhibiting similar leaf
      symptomology to West African CSSD-affected plants was also included in the study
      and the corresponding sequence represents the genome of a new virus named cacao
      bacilliform SriLanka virus (CBSLV).

PMID- 29169833
TI  - Molecular characterization of variants of a new 'rule-breaking' tobacco rattle
      virus RNA2 in potatoes.
AB  - In potato tubers showing pronounced corky ringspot symptoms, two related 'rule
      breaking" tobacco rattle virus (TRV) RNA2s, named Da-2 and Db-2, were identified.
      Their coat protein (cp) genes are preceded on the 5' side by an additional gene
      for a 35 kDa protein for which no relationships with previously described TRV
      genes or their expression products were found. With estimated 4296 and 4247
      nucleotides (nts) the two RNAs are the longest TRV RNA2s described so far. The
      difference in size between Da-2 and Db-2 is due to a duplication of a stretch of
      49 nts in the 5' untranslated region of Da-2. An alignment of TRV coat proteins
      (cp) revealed that up to about amino acid (aa) 176 they form two rather uniform
      groups. The much shorter C-terminal parts of the cps, however, differ
      considerably in size and composition. With 56 aa this C-terminal part is much
      longer in the Da and Db sequences than in all other TRV cps. It differs in 18
      positions in the two strains whereas their N-terminal 184 aa differ only in two
      positions. - In young potato plants developing from bud-cuttings of TRV Db
      infected potato tubers which had been planted in soil free of virus and nematodes
      a gradual degradation of Db-2 was observed. In the newly formed rootlets already
      five days after planting a deletion of 80 nts was observed in the putative 2b
      gene which in other TRV strains encodes a protein necessary for nematode
      transmission. Thirty three days after planting the entire 2b gene, 119 nts at the
      3'end of the cp gene and a portion of the original 3'untranslated region of Db-2
      had been lost in the newly formed roots, leaves and stolons. The gene for the
      35kDa protein was the only one which was not affected by deletions which seems to
      emphasize its importance for the virus. Fifty days after planting only TRV RNA1,
      but no TRV RNA2 were detectable.

PMID- 29169834
TI  - [An ovarian tumor can hide another one].
AB  - We report the case of a 33-year-old woman who went under surgery for a cystic
      mature teratoma. The histological exam found two cysts, one was a mature teratoma
      and the other was a struma ovarii with a papillary carcinomatous element. Struma
      ovarii cancerization is seen in 5 to 10% of the cases usually under a papillary
      carcinoma type. Diagnosis is rarely made before surgery, the patients
      exceptionally show thyroid symptoms. Histologically, the tumour presents the same
      way as the one seen in the thyroid gland and BRAF mutations have been reported.
      The problem concerns ovarian metastases of a thyroid cancer. A normal thyroid
      check up and normal thyroid tissue close to the tumor in the ovary are in favor
      for a cancerize struma ovarii. The therapeutic care is not consensual, going from
      an annexectomy to hysterectomy and bilateral annexectomy. The patients must be
      followed on long-term with thyroglobulin quantitative analysis for at least 10
      years and whole body scintigraphy with iodine 123 to detect relapse or
      metastases. The prognosis is usually good but precise criteria are still to
      define.

PMID- 29169835
TI  - [All large necrotic and hemorrhagic kidney tumors in children are not necessarily
      malignant: A case of a 7-month-old child].
AB  - We report the case of a large tumor in the left kidney with necrotic and
      hemorrhagic features in a 7-month-old child, which was clinically and
      radiologically suggestive of a nephroblastoma. The tumor was a nodular mass
      measuring 8cm in diameter occupying two thirds of the kidney and presenting areas
      of necrosis and hemorrhage. No capsular rupture or renal sinus infiltration were
      found. Adjacent renal parenchyma appeared mascroscopically normal.
      Histologically, the tumor showed a strictly tubulopapillary architectural pattern
      with numerous psammomas. The initial hypothesis was a purely epithelial
      nephroblastoma. However, this hypothesis was rejected due to some
      immunohistochemical and histological characteristics and the final diagnosis was
      a metanephric adenoma. Metanephric adenoma is an exceptionally rare benign renal
      tumor in children. However, pathologists need to keep it in mind because simple
      surgical excision is curative.

PMID- 29169836
TI  - [Classification of pancreatic neuroendocrine tumours: Changes made in the 2017
      WHO classification of tumours of endocrine organs and perspectives for the
      future].
AB  - The WHO classification of the tumors of endocrine organs, published in July 2017,
      has introduced significant changes in the classification of pancreatic
      neuroendocrine tumors, the previous version of which has appeared in 2010, within
      the WHO classification of the tumors of the digestive system. The main change is
      the introduction of a new category of well-differentiated neoplasms,
      neuroendocrine tumors G3, in addition to the previous categories of
      neuroendocrine tumors G1 and G2. The differential diagnosis between
      neuroendocrine tumors G3 (well-differentiated) and neuroendocrine carcinomas
      (poorly-differentiated) might be difficult; the authors of the WHO classification
      therefore suggest the use of a number of immunohistochemical markers to
      facilitate the distinction between the two entities. The other changes are: (a)
      the modification of the threshold between neuroendocrine tumors G1 and G2, now
      set at 3%; (b) the terminology used for mixed tumors: the previous term mixed
      adeno-neuroendocrine carcinoma (MANEC) is substituted by the term mixed
      neuroendocrine-non neuroendocrine neoplasm (MiNEN). Finally, the recommendations
      for Ki-67 index evaluation are actualized. Even if these changes only concern,
      stricto sensu, the neuroendocrine tumors of pancreatic location, they will
      probably be applied, de facto, for all digestive neuroendocrine tumors. The
      revision of the histological classification of pancreatic neuroendocrine tumors
      coincides with the revision of their UICC TNM staging; significant changes have
      been made in the criteria for T3 and T4 stages. Our professional practices have
      to take into account all these modifications.

PMID- 29169837
TI  - [Pseudo-cutaneous tumor in a renal transplant patient].

PMID- 29169838
TI  - Mitigation of electroencephalographic and cardiovascular responses to castration
      in Bos indicus bulls following the administration of either lidocaine or
      meloxicam.
AB  - OBJECTIVE: To investigate the mitigating effects of administration of local
      anaesthetic or systemic meloxicam on the electroencephalographic (EEG) and
      cardiovascular responses during surgical castration of Bos indicus bull calves.
      STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: Thirty-six 6
      8 month-old Bos indicus bull calves, with a mean +/- standard deviation weight of
      237 +/- 19 kg. METHODS: Animals were allocated randomly to three groups of 12
      (group L, 260 mg of 2% lidocaine subcutaneously and intratesticularly 5 minutes
      prior to castration; group M, 0.5 mg kg-1 of meloxicam subcutaneously 30 minutes
      prior to castration; group C, no preoperative analgesia administered).
      Anaesthesia was induced and maintained with halothane (0.9-1.1%) in oxygen.
      Electroencephalogram, heart rate (HR) and mean blood pressure (MAP) were recorded
      for 300 seconds prior to (baseline, B) and from the start of surgery (first
      testicle removal, T1). HR and MAP were compared at 10 second intervals for 90
      seconds from the start of T1. Median frequency (F50), spectral edge frequency
      (F95) and total power of the EEG (Ptot) were analysed using area under the curve
      comparing T1 to B. RESULTS: All EEG variables were significantly different
      between B and T1 (p <= 0.0001). No differences in F50 were found between groups
      during T1 (p = 0.6491). F95 and Ptot were significantly different between group L
      and groups C and M during T1 (p = 0.0005 and 0.0163, respectively). There were
      transient significant changes in HR and MAP in groups L and M compared to group C
      during the 20-50 second periods. CONCLUSIONS: The EEG changes indicate
      nociceptive responses in all three groups during surgical castration, greater in
      group L compared to groups C and M. Both analgesics attenuated the peracute
      cardiovascular response. Lidocaine and meloxicam administered prior to castration
      attenuated these responses in Bos indicus bull calves. CLINICAL RELEVANCE: These
      findings provide support for the preoperative administration of lidocaine and
      potentially meloxicam for castration in Bos indicus bull calves.

PMID- 29169839
TI  - Cardiopulmonary effects of anaesthesia maintained by propofol infusion versus
      isoflurane inhalation in cheetahs (Acinonyx jubatus).
AB  - OBJECTIVE: To compare the cardiopulmonary effects of propofol total intravenous
      anaesthesia (TIVA) with isoflurane in cheetahs (Acinonyx jubatus) to evaluate
      feasibility for field use. STUDY DESIGN: Prospective clinical study. ANIMALS: A
      group of 24 adult cheetahs, 12 per group. METHODS: Cheetahs were immobilized with
      zolazepam/tiletamine (1.2 mg kg-1) and medetomidine [40 MUg kg-1, both
      intramuscular (IM)] by darting. A maintenance protocol of propofol TIVA (group P)
      or isoflurane inhalation (group I) was assigned randomly to each cheetah.
      Anaesthesia was maintained for at least 60 minutes. Cheetahs breathed
      spontaneously throughout; oxygen was supplemented at 3 L minute-1.
      Cardiopulmonary parameters were recorded at 5 minute intervals and three arterial
      blood gas samples were analysed. Following maintenance, atipamezole was
      administered IM (200 MUg kg-1) and recovery was observed. Data are reported as
      mean+/-standard deviation; variables over time were compared using a linear mixed
      model (fixed: time, treatment; random: cheetah). RESULTS: Lack of response to
      manipulations was maintained in all cases (end-tidal isoflurane percentage 1.1+/
      0.1%, propofol rate maintained at 0.1 mg kg-1 minute-1). The heart and
      respiratory rates were acceptable throughout maintenance. The end-tidal carbon
      dioxide tension increased slowly [44.0+/-5.0 mmHg (5.87+/-0.67 kPa)] with no
      differences between groups. All cheetahs were initially markedly hypertensive
      [mean arterial blood pressure (MAP): (163+/-17 mmHg)]. The MAP normalized for
      group I (125+/-30 mmHg) but remained high for group P (161+/-17 mmHg) (p <
      0.001). Arterial carbon dioxide tension [48.9+/-14.6 mmHg (6.52+/-1.95 kPa)]
      never differed between groups. Initial arterial oxygen tension indicated
      borderline hypoxaemia, but improved with oxygen supplementation. Recovery time
      was 10.8+/-5.0 and 51.9+/-23.5 minutes for group I and group P, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: Both protocols provided acceptable
      cardiopulmonary values. Propofol may be an alternative to isoflurane for field
      use, but the prolonged recovery may make it less suitable for long-term
      anaesthesia.

PMID- 29169840
TI  - Cardiovascular effects, induction and recovery characteristics and alfaxalone
      dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous
      anaesthesia in dogs.
AB  - OBJECTIVE: To compare cardiovascular effects and anaesthetic quality of
      alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI)
      when used for total intravenous anaesthesia (TIVA) in dogs. STUDY DESIGN:
      Prospective, blinded, randomized, experimental study. ANIMALS: A group of 12
      intact female dogs. METHODS: Following intramuscular dexmedetomidine (10 MUg kg
      1) and methadone (0.1 mg kg-1) administration, anaesthesia was induced
      intravenously with alfaxalone (2 mg kg-1) (group AP) or alfaxalone (2 mg kg-1)
      preceded by fentanyl (2 MUg kg-1) (group AF). Anaesthetic maintenance was
      obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg-1
      minute-1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI
      of fentanyl (10 MUg kg-1 hour-1) (group AF). The alfaxalone VRI was adjusted
      every 5 minutes, based on clinical assessment. Cardiovascular parameters
      (recorded every 5 minutes) and recovery characteristics (using a numerical rating
      scale) were compared between groups. A mixed model statistical approach was used
      to compare the mean VRI alfaxalone dose and cardiovascular parameters between
      groups; recovery scores were analysed using the Wilcoxon rank-sum test (alpha =
      0.05). RESULTS: The mean CRI alfaxalone dose for anaesthetic maintenance differed
      significantly between treatments [0.16 +/- 0.01 mg kg-1 minute-1 (group AP)
      versus 0.13 +/- 0.01 mg kg-1 minute-1 (group AF)]. Overall heart rate, systolic,
      mean and diastolic arterial pressures were lower in group AF than in group AP (p
      < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality
      scores did not differ significantly and were poor in both groups. CONCLUSIONS AND
      CLINICAL RELEVANCE: In combination with a fentanyl CRI, an alfaxalone TIVA
      provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl
      results in a significant dose reduction. The quality of anaesthetic recovery
      remains poor.

PMID- 29169841
TI  - Distribution and neurochemistry of porcine urinary bladder-projecting sensory
      neurons in subdomains of the dorsal root ganglia: A quantitative analysis.
AB  - The aim of the present study has been to verify the inter- and intraganglionic
      distribution pattern of porcine urinary bladder-projecting (UBP) neurons
      localized in the sacral dorsal root ganglia (DRGs). The morphology and chemical
      phenotype of these cells have also been investigated. These neurons were
      visualized using the fluorescent tracer Fast Blue (FB) which was injected
      bilaterally into the urinary bladder wall of five juvenile female pigs. The
      intraganglionic distribution showed that small- and medium-sized FB+ perikarya
      were mainly located in the central (S3-S4) and periphero-central (S2) region of
      the ganglia, while large cells were heterogeneously distributed.
      Immunohistochemistry revealed that the most frequently observed markers in small
      and medium-sized UBP perikarya were: neurofilament 200, lectin from Bandeiraea
      simplicifolia (Griffonia simplicifolia) isolectin B4, substance P, calcitonin
      gene-related peptide, pituitary adenylate cyclase-activating polypeptide and
      transient receptor potential vanilloid 1. Moreover, UBP neurons containing these
      substances were also mainly observed in the central and periphero-central region
      of the ganglion. Differences in the percentage of traced cells and their
      neuropeptide content were observed between the S2, S3 and S4 DRGs. In conclusion,
      the present study, for the first time, describes the arrangement of UBP DRGs
      neurons within particular subdomains of sacral ganglia, taking into account their
      size and chemical phenotype.

PMID- 29169842
TI  - Anatomic characterization of the radial and ulnar nutrient arteries in humans.
AB  - BACKGROUND: The localization of nutrient foramens has been extensively studied in
      humans and other vertebrate animals. However, accurate information on the origin
      and extraosseous course of the nutrient arteries in some types of long tubular
      bones is lacking. Terminologia Anatomica, the international standard on human
      anatomic terminology, lists the radial nutrient artery (RNA) and the ulnar
      nutrient artery (UNA) as branches of the radial and ulnar arteries, respectively.
      Anatomy textbooks published in both German- and English-speaking countries regard
      both the RNA and UNA as branches of the anterior interosseous artery. METHODS: To
      clarify the anatomic characteristics of the RNA and UNA in humans, we reexamined
      the origin and course of these arteries by cadaveric dissection. RESULTS: Almost
      all RNAs and UNAs branched from the ulnar artery or its tributaries. In typical
      cases, the RNA branched from the anterior interosseous artery and the UNA
      branched from the proximal part of the ulnar artery or the anterior interosseous
      artery. These findings are reasonable from the perspective of regional anatomy,
      since the ulnar artery passes more deeply than the radial artery in the proximal
      forearm and thus the proximal part of the ulnar artery and its major branches are
      situated more closely to the radial and ulnar nutrient foramens. CONCLUSIONS:
      Based on our findings, it is necessary to correct the position of the RNA and UNA
      in the arterial hierarchy of T. Anatomica for accurate morphological description.

PMID- 29169843
TI  - Diagnostic evaluation of patients presenting with hematuria: An electronic health
      record-based study.
AB  - BACKGROUND: To gain new insights into the origin and prevention of diagnostic
      delays in the evaluation of hematuria in an electronic health record (EHR)-based
      integrated care setting. METHODS: We performed a retrospective review of 298
      consecutive patients with new-onset hematuria at a Veterans Affairs facility from
      January 1, 2011 to December 31, 2013 excluding those where diagnostic evaluation
      was unnecessary (i.e., cystoscopy within 3 years prior). We collected data on
      presentation, such as red flags of painless gross hematuria (PGH) or asymptomatic
      microhematuria (AMH) and subsequent evaluation (imaging, urologic referral, and
      cystoscopy). Delay was defined when evaluation was not completed within 60 days.
      Logistic regression was performed to identify predictors of delay. RESULTS: Of
      201 patients, 149 had delays. PGH was present in 99 patients. These patients had
      a higher rate of urology referral within 1 year than patients with AMH (86.7% vs.
      64.7%; P<0.01) and were more likely to undergo cystoscopy (75.8% vs. 52%;
      P<0.01). Delays occurred in 67% of PGH patients vs. 81% of AMH patients (OR 0.46;
      P = 0.02), and roughly a third were related to scheduling/coordination, patient
      related issues, or delay in primary care referral. Bladder neoplasms were
      detected in 18% of patients with PGH and 2% of those with AMH. CONCLUSION: Delays
      in evaluation for hematuria occur commonly, regardless of strength of the red
      flag. Many delays were preventable and could be targeted with interventions
      including EHR-based tracking systems or reformed scheduling practices.

PMID- 29169844
TI  - Fertility preservation for men with testicular cancer: Is sperm cryopreservation
      cost effective in the era of assisted reproductive technology?
AB  - INTRODUCTION: Many patients do not cryopreserve sperm before undergoing cancer
      treatment because of high perceived costs of cryopreservation. We sought to
      investigate the cost-effectiveness of fertility preservation compared to
      posttherapeutic fertility treatment in testicular cancer patients. MATERIALS AND
      METHODS: We performed a systematic search of the PubMed database for the
      following: risk of azoospermia 12 months after surveillance, chemotherapy,
      retroperitoneal lymph node dissection, and radiation therapy (RT); rates of
      natural conception, and rates of conception with the use of intrauterine
      insemination or assisted reproductive technology, with or without microsurgical
      testicular sperm extraction (microTESE). A decision tree was constructed using
      the TreePlan add-in for Microsoft Excel (TreePlan Software, San Francisco,
      California). Cost-effectiveness was calculated as the overall cost of a given
      management branch, divided by likelihood of pregnancy. Calculations accounted for
      variable number of years of cryopreservation, and variable costs of microTESE.
      RESULTS: 1,113 articles were identified; 44 were included in the final analysis.
      Overall probability of pregnancy was higher among couples who cryopreserved
      sperm, versus those who did not. In patients undergoing active surveillance or
      retroperitoneal lymph node dissection, cryopreservation was more cost-effective
      if storage time was short (<6 years) or microTESE cost was high (>7,000).
      Cryopreservation prior to chemotherapy was more cost-effective unless microTESE
      cost was low (<7,000). Cryopreservation prior to RT was more cost-effective in
      almost all scenarios. CONCLUSIONS: Sperm cryopreservation prior to undergoing
      chemotherapy or RT remains the most cost-effective strategy for fertility
      preservation, across a range of possible costs associated with surgical sperm
      retrieval and in vitro fertilization/intracytoplasmic sperm injection.

PMID- 29169845
TI  - Impact of adequate pelvic lymph node dissection on overall survival after radical
      cystectomy: A stratified analysis by clinical stage and receipt of neoadjuvant
      chemotherapy.
AB  - PURPOSE: An adequate pelvic lymph node dissection (LND) during radical cystectomy
      (RC) for muscle-invasive bladder cancer (BCa) has been shown to provide a
      survival benefit. We designed a study to assess the effect of adequate LND on
      overall survival (OS) according to cT stage and receipt of neoadjuvant
      chemotherapy (NAC). MATERIAL AND METHODS: We identified 16,505 patients with
      localized BCa who received RC in the National Cancer Database (2004-2012).
      Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox
      regression analyses were used to compare OS between patients who received
      adequate LND (defined as >=10 nodes removed) and those who did not, stratified by
      cT stage and receipt of NAC. RESULTS: Overall 8,673 (52.55%) patients underwent
      adequate LND at RC for localized BCa. Median time to last follow-up was 55.49
      months (IQR, 34.73-75.96 months). IPTW-adjusted Kaplan-Meier curves showed that
      median OS was improved in patients who received adequate LND (60.06 vs. 46.88
      months). In patients who did not receive NAC, adequate LND was associated with an
      OS benefit for cT1/a/cis, cT2, and cT3/4 disease (P <= 0.008). Among patients who
      received NAC, adequate LND was not associated with any OS difference regardless
      of cT stage. CONCLUSION: Our data suggest that patients who did not receive NAC
      benefit from an adequate LND. However, the receipt of an adequate LND was not
      associated with an OS benefit in patients pretreated with NAC. Our study
      indicates that the receipt of NAC may eradicate micrometastatic disease, and thus
      limit the benefit of an adequate LND.

PMID- 29169847
TI  - Estimating the healthcare costs of treating prostate cancer in Australia: A
      Markov modelling analysis.
AB  - PURPOSE: To estimate the health system costs of prostate cancer by disease risk
      category and treatment type over 2016 to 2025 and to identify potential
      strategies to contain the cost increase. METHODS: A Markov cohort model was
      developed using clinical pathways from US prostate cancer guidelines and clinical
      expertise. Estimates of the probabilities of various treatments and outcomes and
      their unit costs were sourced from systematic reviews, meta-analyses,
      epidemiological publications and national cost reports. Estimated costs by stage
      of disease, by major treatments and by age at diagnosis were reported in 2016 US
      dollars. One-way and probabilistic sensitivity analyses assessed potential
      variation in the modeled costs. RESULTS: Australia-wide costs of prostate cancer
      were estimated at US$270.9 million in 2016 rising to US$384.3 million in 2025, an
      expected increase of 42%. Of this total increase, newly diagnosed low risk cases
      will contribute US$32.9 million, intermediate-risk US$56.8 million, high-risk
      US$53.3 million and advanced US$12.6 million. For men diagnosed at age 65 with
      low-risk disease, lifetime costs per patient were US$14,497 for surgery,
      US$19,665 for radiation therapies to the primary lesion, and US$9,234 for active
      surveillance. For intermediate- or high-risk disease, mean costs per patient were
      US$34,941 for surgery plus radiation and US$31,790 for androgen deprivation
      therapy plus radiation while advanced cancer therapies were at US$31,574 per
      patient. Additional costs for managing iatrogenic disease secondary to these
      treatments were excluded. CONCLUSION: Strategies for identifying patients early
      before cancers have spread are critical to contain the estimated 42% increase in
      costs over the next decade. Increased uptake of active surveillance would also
      lead to substantial cost-savings in the management of low-risk prostate cancer.

PMID- 29169846
TI  - PBRM1 and VHL expression correlate in human clear cell renal cell carcinoma with
      differential association with patient's overall survival.
AB  - OBJECTIVE: To identify the clinicopathological association of PBRM1 (Polybromo-1
      gene) and VHL (von Hippel-Lindau gene) expression at mRNA and protein levels in
      clear cell renal cell carcinoma (ccRCC) and its role in tumor progression.
      PATIENTS AND METHODS: Immunohistochemical analysis, Western blotting and qPCR
      analysis of PBRM1 and VHL were performed on fresh-frozen ccRCC and adjacent
      normal tissue obtained from 70 patients who underwent radical nephrectomy. In
      addition, a tissue microarray (TMA) from specimens of 326 ccRCC patients was used
      to evaluate the effect of loss of PBRM1 and VHL immunohistological expression on
      clinicopathological features as well as patient survival. RESULTS: In frozen
      tissue, PBRM1 and VHL mRNA were significantly down-regulated in most ccRCC tumors
      (77.6%/80.6%). Simultaneous weak PBRM1 and VHL protein expression was observed in
      21.4% of frozen tumors. In the TMA samples, weak PBRM1 and VHL
      immunohistochemical staining was observed in 60.4% of the cases and was
      correlated (P<0.001). The association of PBRM1 and VHL immunohistochemical
      expression with clinicopathological parameters depicts a variable picture:
      predominantly weak PBRM1 and VHL expression were significantly associated with
      higher Fuhrman grade (P = 0.012 and 0.024, respectively) but only weak VHL
      expression was associated with a higher pT stage (P = 0.023). PBRM1 expression
      did not affect the overall survival, whereas weak VHL expression was associated
      with decreased patient overall survival (P = 0.013). CONCLUSIONS: Our data
      suggest that reduced expression of PBRM1 and VHL is correlated with an increased
      tumor aggressiveness. Low VHL expression was identified as a risk factor for
      worse patient overall survival, independently from PBRM1 expression pattern.

PMID- 29169848
TI  - LC3-associated phagocytosis in microbial pathogenesis.
AB  - Phagocytosis is essential for uptake and elimination of pathogenic
      microorganisms. Autophagy is a highly conserved mechanism for incorporation of
      cellular constituents to replenish nutrients by degradation. Recently, parts of
      the autophagy machinery - above all microtubule-associated protein 1 light chain
      3 (LC3) - were found to be specifically recruited to phagosomal membranes
      resulting in phagosome-lysosome fusion and efficient degradation of internalized
      cargo in a process termed LC3-associated phagocytosis (LAP). Many pathogenic
      bacterial, fungal and parasitic microorganisms reside within LAP-targeted single
      membrane phagosomes or vacuoles after infection of host cells. In this minireview
      we describe the state of knowledge on the interaction of pathogens with LAP or
      LAP-like pathways and report on various pathogens that have evolved strategies to
      circumvent degradation in LAP compartments.

PMID- 29169850
TI  - Family-based analysis of GGT1 and HNF1A gene polymorphisms in patients with
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disease.
      Previous studies indicate that genes GGT1 and HNF1A may contribute to the
      abnormal glucose metabolism and altered lipid profile that are important clinical
      features of PCOS. In the current study, the correlation between polymorphisms in
      the GGT1 and HNF1A genes and PCOS was explored. A total of 310 family trios were
      studied and the transmission disequilibrium test (TDT) was used to assess the
      linkage between PCOS and three single-nucleotide polymorphisms (SNP) (rs4820599
      of GGT1, rs7305618 and rs2393791 of HNF1A). No deviations from HWE were detected.
      None of the three SNP markers showed significant transmission disequilibrium in
      PCOS family trios (rs4820599: GGT1 gene, chi2 = 1.067; rs7305618: HNF1A gene,
      chi2 = 0.013; rs2393791: HNF1A gene, chi2 = 0.031). In conclusion, no significant
      evidence supported a relationship between genes GGT1 and HNF1A and PCOS in the
      current family trios.

PMID- 29169849
TI  - Disconnection of basolateral amygdala and insular cortex disrupts conditioned
      approach in Pavlovian lever autoshaping.
AB  - Previously established individual differences in appetitive approach and
      devaluation sensitivity observed in goal- and sign-trackers may be attributed to
      differences in the acquisition, modification, or use of associative information
      in basolateral amygdala (BLA) pathways. Here, we sought to determine the extent
      to which communication of associative information between BLA and anterior
      portions of insular cortex (IC) supports ongoing Pavlovian conditioned approach
      behaviors in sign- and goal-tracking rats, in the absence of manipulations to
      outcome value. We hypothesized that the BLA mediates goal-, but not sign-
      tracking approach through interactions with the IC, a brain region involved in
      supporting flexible behavior. We first trained rats in Pavlovian lever
      autoshaping to determine their sign- or goal-tracking tendency. During
      alternating test sessions, we gave unilateral intracranial injections of vehicle
      or a cocktail of gamma-aminobutyric acid (GABA) receptor agonists, baclofen and
      muscimol, unilaterally into the BLA and contralaterally or ipsilaterally into the
      IC prior to reinforced lever autoshaping sessions. Consistent with our hypothesis
      we found that contralateral inactivation of BLA and IC increased the latency to
      approach the food cup and decreased the number of food cup contacts in goal
      trackers. While contralateral inactivation of BLA and IC did not affect the total
      number of lever contacts in sign-trackers, this manipulation increased the
      latency to approach the lever. Ipsilateral inactivation of BLA and IC did not
      impact approach behaviors in Pavlovian lever autoshaping. These findings,
      contrary to our hypothesis, suggest that communication between BLA and IC
      maintains a representation of initially learned appetitive associations that
      commonly support the initiation of Pavlovian conditioned approach behavior
      regardless of whether it is directed at the cue or the location of reward
      delivery.

PMID- 29169851
TI  - A novel homozygous mutation of bone morphogenetic protein 15 identified in a
      consanguineous marriage family with primary ovarian insufficiency.
AB  - The aim of this study was to explore the pathogenic gene in a primary ovarian
      insufficiency (POI) patient from a consanguineous marriage family. The proband
      and her healthy mother were selected for whole-exome sequencing. By applying a
      strict filtering strategy, we found a novel homozygous missense mutation,
      c.G1070A (p.C357Y), of BMP15 in the proband, whereas her mother was heterozygous
      for this mutation. The mutation was highly conserved among species and predicted
      to be disorder causing. This study has revealed a novel homozygous mutation of
      the BMP15 gene that may be associated with POI.

PMID- 29169852
TI  - Atovaquone/proguanil (Maloff Protect) is now available without prescription in UK
      pharmacies.

PMID- 29169854
TI  - Correction to Lancet Glob Health 2017; 5: e1186-87.

PMID- 29169853
TI  - Colony formation in solid medium by the relapsing fever spirochetes Borrelia
      hermsii and Borrelia turicatae.
AB  - Relapsing fever (RF) in North America is caused primarily by the spirochete
      Borrelia hermsii and is associated with the bite of its tick vector Ornithodoros
      hermsi. Although this spirochete was known long before the discovery of the Lyme
      disease (LD) spirochete, Borrelia burgdorferi, basic methods to facilitate the
      study of B. hermsii have lagged behind. One important technique to expedite the
      study of the molecular biology and pathogenesis of B. hermsii would be a reliable
      method to grow and clone these bacteria in solid medium, which we now describe.
      We have defined the solidifying agent, plating temperature, oxygen concentration,
      and pH for the efficient plating of two species of RF spirochetes, B. hermsii and
      Borrelia turicatae. Importantly, this technique allowed us to successfully
      isolate virulent, clonal cell lines of spirochetes, and to enumerate and isolate
      viable B. hermsii from infected mouse blood and tick tissues. Our results also
      demonstrate the value of testing a range of several environmental variables to
      increase the efficiency of bacterial isolation, which may be helpful for
      researchers working on other prokaryotes that are intractable for in vitro
      growth.

PMID- 29169855
TI  - Hypertensive complications of pregnancy: A clinical overview.
AB  - Hypertensive disorders in pregnancy are a worldwide health problem for women and
      their infants complicating up to 10% of pregnancies and associated with increased
      maternal and neonatal morbidity and mortality. In Europe, 2.3-3% of pregnancies
      are complicated by preeclampsia. Gestational diabetes, obesity, no previous or
      multiple births, maternal age less than 20 or greater than 35years old and
      thrombophilia can be some of the possible factors related to increased risk for
      hypertension in pregnancy. Complications of hypertension during pregnancy affect
      both mothers and their infants. Ambulatory blood pressure monitoring helps to
      distinguish true hypertension from the white coat as pregnant women with office
      abnormal values may have normal out of office blood pressure. Imbalance between
      proangiogenic and antiangiogenic factors in placenta may lead to endothelial
      dysfunction, vasoconstriction, activation of the coagulation system, and
      hemolysis. Carotid intima-media thickness, pulse wave velocity, augmentation
      index, and arterial wall tension were found to be significantly increased in
      women with preeclampsia compared to normotensive pregnant women. Uterine artery
      Doppler and serum biomarkers can be used to evaluate the probability of
      hypertension and complications during pregnancy, but further research in the
      field is needed. Lately, micro ribonucleic acids have also been the focus of
      research as potential biomarkers.

PMID- 29169856
TI  - Comparing the accuracy of medication order verification between pharmacists and a
      tech check tech model: A prospective randomised observational study.
AB  - BACKGROUND: Medication errors have the potential to cause significant harm and
      the final verification of dispensed medications is essential to patient safety.
      There is international evidence to demonstrate that trained pharmacy technicians
      can safely and accurately undertake the verification of medication orders in ward
      based unit dose containers. There is a need for evaluation of pharmacy technician
      verification of medication orders in broader contexts including the hospital
      inpatient dispensary. AIM: To compare the accuracy of Accuracy Checking Pharmacy
      Assistants (ACPTs) to pharmacists when verifying inpatient medication orders
      within the hospital pharmacy setting. METHOD: This 'real world' single-blinded
      study was conducted in the inpatient dispensary of a major tertiary hospital in
      Melbourne, Australia. Inpatient medication orders were randomly allocated to an
      ACPT or pharmacist for final verification, before being reviewed for accuracy by
      an independent research pharmacist blinded to study allocation. Errors identified
      by the reviewing pharmacist were documented and severity was assessed by an
      independent Medication Safety pharmacist. RESULTS: Between February and August
      2014, three ACPTs verified 4718 items with 75 errors missed (1.59%), and twelve
      pharmacists verified 4194 items with 158 errors missed (3.77%). There was a
      statistically significant difference between both total and minor error rates,
      with pharmacists missing significantly more errors (total errors: p < 0.0001;
      minor errors: 1.42 vs 3.53%; p < 0.0001). There was no statistically significant
      difference in the rate of major errors missed by the two groups (0.17 vs 0.24%; p
      = 0.48). CONCLUSION: This study is the first of its kind in the hospital
      dispensary setting, demonstrating that the overall accuracy of ACPTs was greater
      than pharmacists for verifying dispensed medication orders. ACPTs missed fewer
      minor and overall errors than pharmacists, indicating that trained pharmacy
      technicians can verify medication orders safely and accurately. This study
      provides support for the tech-check-tech model in the hospital setting.

PMID- 29169857
TI  - Development and validation of new predictive equation for resting energy
      expenditure in adults with overweight and obesity.
AB  - BACKGROUND & AIMS: Accurate predictive equations of resting energy expenditure
      (REE) are crucial in devising nutritional strategies to manage
      overweight/obesity, especially in countries where these are highly prevalent. REE
      is the most common measurement used to estimate energy requirements in the
      nutritional context; the most accurate method of measuring REE is indirect
      calorimetry (IC). However, this method is costly and often rarely feasible in
      many clinical settings. The objective of the present study was to develop and
      validate a new equation for predicting REE in adults with overweight and obesity.
      METHODS: This was a cross-sectional study including 410 men and women with
      overweight and obesity (20-60 y). Participants were randomly assigned; the
      development group included 200 subjects and the validation group 210 subjects.
      The new predictive equation was derived using stepwise multiple linear regression
      analysis. The accuracy of the new equation was compared to several existing
      predictive equations (PEs). The accuracy rate was calculated as the percentage of
      subjects whose REE-PE was within +/-10% of the REE-IC. REE was measured by IC and
      anthropometric measurements. RESULTS: One predictive equation was developed (NEQ)
      in which weight was the strongest predictor of REE. Compared with others
      predicted equations already using, the new designed equation showed the less mean
      bias (Kj/day): NEQ: 25.7, Valencia:129, WHO/FAO/United Nations University: 270,
      Mifflin-St Jeor: 308, Owen: -808, Carrasco: -1097, Korth: -36.4, Johnstone: -375,
      Livingstone: -315, De Lorenzo: -28.3, Lazzer: -123, Muller: -145, Huang: -399 and
      Bernstein: -1335. CONCLUSIONS: The present equation had the highest predictive
      accuracy in subjects with overweight or obesity compared with the previous
      equations derived from different populations. Thus, these new equation can be
      used to assist the nutritional management of these subjects.

PMID- 29169858
TI  - Epicardial adipose tissue, alcohol consumption, and coronary artery disease
      severity.

PMID- 29169859
TI  - A model based on feature objects aided strategy to evaluate the methane
      generation from food waste by anaerobic digestion.
AB  - A model based on feature objects (FOs) aided strategy was used to evaluate the
      methane generation from food waste by anaerobic digestion. The kinetics of
      feature objects was tested by the modified Gompertz model and the first-order
      kinetic model, and the first-order kinetic hydrolysis constants were used to
      estimate the reaction rate of homemade and actual food waste. The results showed
      that the methane yields of four feature objects were significantly different. The
      anaerobic digestion of homemade food waste and actual food waste had various
      methane yields and kinetic constants due to the different contents of FOs in food
      waste. Combining the kinetic equations with the multiple linear regression
      equation could well express the methane yield of food waste, as the R2 of food
      waste was more than 0.9. The predictive methane yields of the two actual food
      waste were 528.22 mL g-1 TS and 545.29 mL g-1 TS with the model, while the
      experimental values were 527.47 mL g-1 TS and 522.1 mL g-1 TS, respectively. The
      relative error between the experimental cumulative methane yields and the
      predicted cumulative methane yields were both less than 5%.

PMID- 29169860
TI  - Maize cob waste pre-treatments to enhance biogas production through co-anaerobic
      digestion with OFMSW.
AB  - In the present work, the enhancement of biogas and methane yields through
      anaerobic co-digestion of the pre-hydrolised Organic Fraction of Municipal Solid
      Wastes (hOFMSW) and Maize Cob Wastes (MCW) in a lab-scale thermophilic anaerobic
      reactor was tested. In order to increase its biodegradability, MCW were submitted
      to an initial pre-treatment screening phase as follows: (i) microwave (MW)
      irradiation catalysed by NaOH, (ii) MW catalysed by glycerol in water and
      alkaline water solutions, (iii) MW catalysed by H2O2 with pH of 9.8 and (iv)
      chemical pre-treatment at room temperature catalysed by H2O2 with 4 h reaction
      time. The pre-treatments cataysed by H2O2 were performed with 2% MCW (wMCW/v
      alkaline water) at ratios of 0.125, 0.25, 0.5 and 1.0 (wH2O2/wMCW). The pre
      treatment that presented the most favourable balance between sugars, lignin,
      cellulose and hemicellulose solubilisations, as well as low production of
      phenolic compound and furfural (inhibitors), was the chemical pre-treatment
      catalysed by H2O2, at room temperature, with a ratio of 0.5 wH2O2/wMCW (Pre1).
      This Pre1 was then optimised testing reaction times of 1, 2 and 3 days at a
      different pH (11.5) and MCW percentage (10% w/v). The optimised pre-treatment
      that presented the best results, considering the same criteria defined above, was
      the one carried out during 3 days, at pH 9.8 and 10% MCW w/v (Pre2). The
      anaerobic reactor was initially fed with the hOFMSW obtained from the hydrolysis
      tank of an industrial AD plant. The hOFMSW was than co-digested with MCW
      submitted to the pre-treatment Pre1. In another assay, hOFMSW was co-digested
      with MCW submitted pre-treatment Pre 2. The co-digestion of hOFMSW + Pre1
      increased the biogas yield by 38.9% and methane yield by 29.7%, when compared to
      the results obtained with hOFMSW alone. The co-digestion of hOFMSW + Pre2
      increased biogas yield by 46.0% and CH4 yield by 36.3%. In both cases, the
      methane content obtained in the biogas streams was above 66% v/v. These results
      show that pre-treatment with H2O2, at room temperature, is a promising low cost
      way to valorize MCW through co-digestion with hOFMSW.

PMID- 29169861
TI  - Prevalence of restless legs syndrome during pregnancy: A systematic review and
      meta-analysis.
AB  - Pregnant women are more likely to be affected by restless legs syndrome (RLS)
      than the general population. Restless legs syndrome during pregnancy is
      associated with adverse maternal and fetal outcomes. Currently unknown is the
      worldwide and regional prevalence of RLS in pregnant women. We performed a meta
      analysis to provide a full profile of the prevalence of RLS during pregnancy. A
      systematic search of the PubMed, Medline, EMBASE, and Web of Science databases
      was performed to identify studies that were published up to April 2017, followed
      by random-effects meta-analyses. A total of 196 articles were identified, among
      which 27 longitudinal and cross-sectional observational studies with 51,717
      pregnant subjects were included in the analysis. The pooled overall prevalence of
      RLS across all three trimesters was 21%. According to the regional classification
      of the World health organization, the prevalence of RLS during pregnancy in the
      European Region, Western Pacific Region, Eastern Mediterranean Region, and Region
      of the Americas was 22%, 14%, 30%, and 20%, respectively. The regional prevalence
      in the African Region and South-East Asia Region was not assessed because of
      insufficient data. We also analyzed the prevalence of RLS in the first, second,
      and third trimesters of pregnancy, and the rates of RLS were 8%, 16%, and 22%,
      respectively. We also found that the high prevalence of RLS decreased to 4% after
      delivery. No publication bias was found in these analyses. The findings emphasize
      the high occurrence of RLS during pregnancy. Future studies should examine the
      effects of RLS during pregnancy on maternal and fetal outcomes.

PMID- 29169862
TI  - Letter to the editor concerning the adverse health effects in children exposed in
      utero to diethylstilbestrol.

PMID- 29169863
TI  - Smartphone apps and the nutrition care process: Current perspectives and future
      considerations.
AB  - OBJECTIVE: To provide dietitians with practical guidance on incorporating
      smartphone applications (apps) in the nutrition care process (NCP) to optimize
      patient education and counseling. METHODS: The current evidence-base for mobile
      health (mHealth) apps was searched using PubMed and Google Scholar. Where and how
      apps could be implemented by dietitians across the four steps of the NCP is
      discussed. RESULTS: With functionality to automatically convert patient dietary
      records into nutrient components, nutrition assessment can be streamlined using
      nutrition apps, allowing more time for dietitians to deliver education and
      nutrition counseling. Dietitians could prescribe apps to provide patients with
      education on nutrition skills and in counseling for better adherence to behavior
      change. Improved patient-provider communication is also made possible through the
      opportunity for real-time monitoring and evaluation of patient progress via apps.
      A practical framework termed the 'Mobile Nutrition Care Process Grid' provides
      dietitians with best-practice guidance on how to use apps. CONCLUSIONS: Including
      apps into dietetic practice could enhance the efficiency and quality of nutrition
      care and counseling delivered by dietitians. PRACTICE IMPLICATIONS: Apps should
      be considered an adjunct to enable dietetic counseling and care, rather than to
      replace the expertise, social support and accountability provided by dietitians.

PMID- 29169864
TI  - Protecting my patients' story: Beneficent or paternalistic?

PMID- 29169865
TI  - Corrigendum to "Dexamethasone, Intravenous Immunoglobulin, and Rituximab
      Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome" [Pediatric
      Neurology 73 (2017) 48-56].

PMID- 29169866
TI  - In Regard to Byrne et al.

PMID- 29169867
TI  - Clinical Considerations Derived From the Administration of Melatonin to Children
      With Sleep Disorders.
AB  - BACKGROUND AND OBJECTIVES: Despite the numerous investigations carried out in
      relation to melatonin, there is a lack of knowledge about the specific melatonin
      secretion patterns in the diverse primary sleep disturbances. The objective of
      this study was to analyze the plasma melatonin concentrations in children with
      primary sleep disorders and the effects of melatonin therapy on their serum
      levels and their actigraphic sleep parameters. METHODS: Fourteen participants
      (nine girls; seven to 14 years old) diagnosed with diverse primary sleep
      disorders were recruited. Four different melatonin secretion patterns were
      identified: low plasma melatonin levels, absence of a circadian rhythm, advanced
      acrophase, and delayed acrophase. A placebo (one week) was administered followed
      by three months of melatonin therapy (3 mg/night). Urinary 6-sulfatoxymelatonin
      levels, 24-hour plasma melatonin concentrations, and a seven-day actigraphic
      record were collected after both treatments. RESULTS: After melatonin therapy, a
      significant increase (P < 0.001) of urinary 6-sulfatoxymelatonin excretion with a
      clear circadian variation was observed. Plasma melatonin concentrations were also
      significantly higher with a recovery in the circadian rhythm. Actual sleep time
      was significantly longer, with a substantial reduction in the sleep onset latency
      and night awakenings. No severe side effects were reported. CONCLUSIONS: The main
      clinical implication of this study is to demonstrate the efficacy of melatonin in
      three main circumstances: an insufficient hormone production, a disturbed
      circadian rhythm, and an advanced or delayed acrophase. As ongoing work, we are
      exploring the effect of different doses of melatonin on the regulation of its
      concentrations and of its secretion rhythm.

PMID- 29169868
TI  - Response to Sharawat and Suther.

PMID- 29169869
TI  - Reply to the Letter to the Editor by Josef Finsterer and Sinda Zarrouk-Mahjoub.

PMID- 29169870
TI  - Dexamethasone-Based Multimodal Therapy for Pediatric Opsoclonus-Myoclonus-Ataxia
      Syndrome: Is It Really Superior?

PMID- 29169871
TI  - Linear atrophy and hypopigmentation after intralesional corticosteroid injection.

PMID- 29169872
TI  - Quercetin improves endothelial function in diabetic rats through inhibition of
      endoplasmic reticulum stress-mediated oxidative stress.
AB  - Endoplasmic reticulum (ER) stress attributes a crucial role in diabetes-induced
      endothelial dysfunction. The present study investigated the effects of quercetin,
      a potent antioxidant on the attenuation of ER stress-modulated endothelial
      dysfunction in streptozotocin (STZ)-induced diabetic rats. Oral administration of
      quercetin for six weeks to diabetic rats dose-dependently reduced the blood
      glucose levels and improved insulin secretion. Histopathological examination of
      pancreatic tissues in diabetic rats showed pathological changes such as shrunken
      islets, reduction in islet area and distorted beta-cells, which were found to be
      restored by quercetin treatment. In addition, quercetin reduced the pancreatic ER
      stress-induced endothelial dysfunction as assessed by immunohistochemical
      analysis of C/ERB homologous protein (CHOP) and endothelin-1 (ET-1). Moreover,
      quercetin administration progressively increased the expression of vascular
      endothelial growth factor (VEGF) and its receptor, VEGFR2 in diabetes rats.
      Quercetin-mediated decrease in the nitric oxide (NO?) and cyclic 3',5'- guanosine
      monophosphate (cGMP) levels were also observed in the diabetic rats. Quercetin
      treatment reduced the lipid peroxidation in the diabetic rats, meanwhile
      increased the total antioxidant capacity in the pancreas from diabetic rats.
      Altogether, these results demonstrated the vasoprotective effect of quercetin
      against STZ-induced ER stress in the pancreas of diabetic rats.

PMID- 29169873
TI  - Modified HyperCVAD Versus Bortezomib-HyperCAD in Patients With
      Relapsed/Refractory Multiple Myeloma.
AB  - INTRODUCTION: Multiple myeloma (MM) is an incurable plasma cell malignancy, in
      which aggressive relapses might require salvage cytotoxic infusional
      chemotherapy. Several clinical trials that reported the efficacy of bortezomib
      led to institutional practice changes in which vincristine was replaced with
      bortezomib in the modified hyperCVAD regimen, creating a new treatment regimen,
      named "bortezomib-hyperCAD." PATIENTS AND METHODS: We retrospectively describe
      the effectiveness and tolerability of 2 chemotherapy regimens among 33 patients
      with relapsed and/or refractory MM. Patients who received >= 1 cycle of modified
      hyperCVAD or bortezomib-hyperCAD between 2011 and 2015 were assessed. RESULTS:
      The median number of cycles administered in each arm was 2. The overall response
      rate was 40% (6 partial responses) in the modified hyperCVAD group and 44.4% (1
      complete response, 1 very good partial response, and 6 partial responses) in the
      bortezomib-hyperCAD group (Fisher exact P = .80). Median progression-free
      survival (PFS) and median overall survival (OS) for patients in the modified
      hyperCVAD group was 6.3 months and 11.1 months, respectively. This was comparable
      with patients in the bortezomib-hyperCAD group, who had a median PFS of 6.6
      months and a median OS of 13.8 months (log rank P = .54 and .66, respectively).
      There was no statistically significant association between treatment arm and
      febrile neutropenia, emergency department visits, hospitalizations, or peripheral
      neuropathy (all Fisher exact P values > .05). CONCLUSION: Overall effectiveness
      and tolerability outcomes were similar between modified hyperCVAD and bortezomib
      hyperCAD, with both regimens showing an impressive response rate among refractory
      and heavily pretreated patients with relapsed MM.

PMID- 29169874
TI  - Intellectual disability in children and teenagers: Influence on family and family
      health. Systematic review.
AB  - OBJECTIVE: To examine the influence of a child or adolescent with intellectual
      disabilities on the family unit. METHOD: A systematic review of the literature,
      following the recommendations of the PRISMA statement, was carried out on the
      PubMed, Scopus, CINAHL, PsycINFO and Psicodoc databases. Original articles were
      found, published in the last 5 years, in Spanish, English, Portuguese, Italian or
      French, with summary and full text and satisfactory or good methodological
      quality. Two independent researchers agreed on their decisions. RESULTS: In
      general, care is provided in the family, mothers assume the greater
      responsibility, and their wellbeing is lower than that of fathers. Having the
      support of the husband improves their quality of life. The fraternal subsystem
      can be affected, with regard to the warmth and the status/power of the
      relationship, and behavioural problems. Family health may be affected in all its
      dimensions: family functioning and atmosphere due to increased demands and
      changes in the organisation and distribution of roles; family resilience and
      family coping, due to rising costs and dwindling resources; family integrity
      could be strengthened by strengthened family ties. Quality of family life is
      enhanced by emotional support. CONCLUSIONS: These families may need
      individualised attention due to the increased demand for care, diminishing
      resources or other family health problems. Nurses using a family-centred care
      approach can identify these families and help them to normalise their situation
      by promoting their family health and the well-being of its members.

PMID- 29169875
TI  - Current and future antenatal management of isolated congenital diaphragmatic
      hernia.
AB  - Congenital diaphragmatic hernia is surgically correctable, yet the poor lung
      development determines mortality and morbidity. In isolated cases the outcome may
      be predicted prenatally by medical imaging. Cases with a poor prognosis could be
      treated before birth. However, prenatal modulation of lung development remains
      experimental. Fetoscopic endoluminal tracheal occlusion triggers lung growth and
      is currently being evaluated in a global clinical trial. Prenatal transplacental
      sildenafil administration may in due course be a therapeutic approach, reducing
      the occurrence of persistent pulmonary hypertension, either alone or in
      combination with fetal surgery.

PMID- 29169876
TI  - EGFR monoclonal antibody biomarkers in advanced NSCLC: from translational
      research to clinical implementation.

PMID- 29169878
TI  - Three-year outcome of the covered endovascular reconstruction of the aortic
      bifurcation technique for aortoiliac occlusive disease.
AB  - OBJECTIVE: The objective of this study was to demonstrate the 3-year outcome of
      the covered endovascular reconstruction of the aortic bifurcation (CERAB)
      technique for the treatment of extensive aortoiliac occlusive disease (AIOD).
      METHODS: Between February 2009 and July 2016, all patients treated with the CERAB
      technique for AIOD were identified in the local databases of two centers and
      analyzed. Demographics and lesion characteristics were scored. Follow-up
      consisted of clinical assessment, duplex ultrasound, and ankle-brachial indices.
      Patency rates and clinically driven target lesion revascularization were
      calculated by Kaplan-Meier analysis. RESULTS: Of 130 patients (69 male and 61
      female) treated, 68% were diagnosed with intermittent claudication and 32%
      suffered from critical limb ischemia. The majority (89%) were TransAtlantic Inter
      Society Consensus II D lesions, and the remaining were B and C lesions (both 5%).
      Median follow-up was 24 months (range, 0-67 months). The technical success rate
      was 97%, and 67% of cases were performed completely percutaneously. The ankle
      brachial index improved significantly from 0.65 +/- 0.22 preoperatively to 0.88
      +/- 0.15 after the procedure. The 30-day minor and major complication rate was
      33% and 7%. The median hospital stay was 2 days (range, 1-76 days). At 1 year and
      3 years of follow-up, 94% and 96% of the patients clinically improved at least
      one Rutherford category (2% and 0% unchanged, 4% and 4% worsened). Limb salvage
      rate was 98% at 1 year and 97% at 3 years of follow-up. Primary, primary
      assisted, and secondary patency was 86%, 91%, and 97% at 1 year; 84%, 89%, and
      97% at 2 years; and 82%, 87%, and 97% at 3 years. Freedom from clinically driven
      target lesion revascularization was 87% at 1-year follow-up and 86% at both 2
      year and 3-year follow-up. CONCLUSIONS: The CERAB technique is a safe and
      feasible technique for the treatment of extensive AIOD with good 3-year results
      regarding patency and clinical improvement.

PMID- 29169877
TI  - Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus
      carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG
      S0819): a randomised, phase 3 study.
AB  - BACKGROUND: EGFR antibodies have shown promise in patients with advanced non
      small-cell lung cancer (NSCLC), particularly with squamous cell histology. We
      hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH)
      can identify patients most likely to benefit from these drugs combined with
      chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy
      in patients with advanced NSCLC who are EGFR FISH-positive. METHODS: We did this
      open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We
      randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to
      receive paclitaxel (200 mg/m2; every 21 days) plus carboplatin (area under the
      curve of 6 by modified Calvert formula; every 21 days) or carboplatin plus
      paclitaxel and bevacizumab (15 mg/kg; every 21 days), either with cetuximab (250
      mg/m2 weekly after loading dose; cetuximab group) or without (control group),
      stratified by bevacizumab treatment, smoking status, and M-substage using a
      dynamic-balancing algorithm. Co-primary endpoints were progression-free survival
      in patients with EGFR FISH-positive cancer and overall survival in the entire
      study population. We analysed clinical outcomes with the intention-to-treat
      principle and analysis of safety outcomes included patients who received at least
      one dose of study drug. This study is registered with ClinicalTrials.gov (number
      NCT00946712). FINDINGS: Between Aug 13, 2009, and May 30, 2014, we randomly
      assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380
      without bevacizumab in the intention-to-treat population) or the cetuximab group
      (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to
      treat population). EGFR FISH was assessable in 976 patients and 400 patients
      (41%) were EGFR FISH-positive. The median follow-up for patients last known to be
      alive was 35.2 months (IQR 22.9-39.9). After 194 progression-free survival events
      in the cetuximab group and 198 in the control group in the EGFR FISH-positive
      subpopulation, progression-free survival did not differ between treatment groups
      (hazard ratio [HR] 0.92, 95% CI 0.75-1.12; p=0.40; median 5.4 months [95% CI 4.5
      5.7] vs 4.8 months [3.9-5.5]). After 570 deaths in the cetuximab group and 593 in
      the control group, overall survival did not differ between the treatment groups
      in the entire study population (HR 0.93, 95% CI 0.83-1.04; p=0.22; median 10.9
      months [95% CI 9.5-12.0] vs 9.2 months [8.7-10.3]). In the prespecified analysis
      of EGFR FISH-positive subpopulation with squamous cell histology, overall
      survival was significantly longer in the cetuximab group than in the control
      group (HR 0.58, 95% CI 0.36-0.86; p=0.0071), although progression-free survival
      did not differ between treatment groups in this subgroup (0.68, 0.46-1.01;
      p=0.055). Overall survival and progression-free survival did not differ among
      patients who were EGFR FISH non-positive with squamous cell histology (HR 1.04,
      95% CI 0.78-1.40; p=0.77; and 1.02, 0.77-1.36; p=0.88 respectively) or patients
      with non-squamous histology regardless of EGFR FISH status (for EGFR FISH
      positive 0.88, 0.68-1.14; p=0.34; and 0.99, 0.78-1.27; p=0.96; respectively; and
      for EGFR FISH non-positive 1.00, 0.85-1.17; p=0.97; and 1.03, 0.88-1.20; p=0.69;
      respectively). The most common grade 3-4 adverse events were decreased neutrophil
      count (210 [37%] in the cetuximab group vs 158 [25%] in the control group),
      decreased leucocyte count (103 [16%] vs 74 [20%]), fatigue (81 [13%] vs 74
      [20%]), and acne or rash (52 [8%] vs one [<1%]). 59 (9%) patients in the
      cetuximab group and 31 (5%) patients in the control group had severe adverse
      events. Deaths related to treatment occurred in 32 (6%) patients in the cetuximab
      group and 13 (2%) patients in the control group. INTERPRETATION: Although this
      study did not meet its primary endpoints, prespecified subgroup analyses of
      patients with EGFR FISH-positive squamous-cell carcinoma cancers are encouraging
      and support continued evaluation of anti-EGFR antibodies in this subpopulation.
      FUNDING: National Cancer Institute and Eli Lilly and Company.

PMID- 29169881
TI  - Why evaluate traditional biomarkers based on archaic sepsis definition?

PMID- 29169880
TI  - Evaluating the Benefit of Elevated Acoustic Output in Harmonic Motion Estimation
      in Ultrasonic Shear Wave Elasticity Imaging.
AB  - Harmonic imaging techniques have been applied in ultrasonic elasticity imaging to
      obtain higher-quality tissue motion tracking data. However, harmonic tracking can
      be signal-to-noise ratio and penetration depth limited during clinical imaging,
      resulting in decreased yield of successful shear wave speed measurements. A
      logical approach is to increase the source pressure, but the in situ pressures
      used in diagnostic ultrasound have been subject to a de facto upper limit based
      on the Food and Drug Administration guideline for the mechanical index (MI <1.9).
      A recent American Institute of Ultrasound in Medicine report concluded that an in
      situ MI up to 4.0 could be warranted without concern for increased risk of
      cavitation in non-fetal tissues without gas bodies if there were a concurrent
      clinical benefit. This work evaluates the impact of using an elevated MI in
      harmonic motion tracking for hepatic shear wave elasticity imaging. The studies
      indicate that high-MI harmonic tracking increased shear wave speed estimation
      yield by 27% at a focal depth of 5 cm, with larger yield increase in more
      difficult-to-image patients. High-MI tracking improved harmonic tracking data
      quality by increasing the signal-to-noise ratio and decreasing jitter in the
      tissue motion data. We conclude that there is clinical benefit to use of elevated
      acoustic output in shear wave tracking, particularly in difficult-to-image
      patients.

PMID- 29169879
TI  - A qualitative study of factors that influence active family involvement with
      patient care in the ICU: Survey of critical care nurses.
AB  - OBJECTIVE: Family caregiver involvement may improve patient and family outcomes
      in the intensive care unit. This study describes critical care nurses' approaches
      to involving family caregivers in direct patient care. RESEARCH METHODOLOGY &
      DESIGN: This is a qualitative content analysis of text captured through an
      electronic survey. SETTING: A convenience sample of 374 critical care nurses in
      the United States who were subscribers to one of the American Association of
      Critical Care Nurses social media sites or electronic newsletters. MAIN OUTCOME
      MEASURE: Critical care nurses' responses to five open-ended questions about their
      approaches to family involvement in direct patient care. FINDINGS: Nurse, patient
      and family caregiver factors intersected in the context of the professional
      practice environment and the available resources for family care. Two main themes
      were identified: "Involving family caregivers in patient care in the intensive
      care unit requires careful ssessment" and "There are barriers and facilitators to
      caregiver involvement in patient care in the intensive care unit." CONCLUSION:
      Patient care demands, the professional practice environment and a lack of
      resources for families hindered nursing family caregiver involvement. Greater
      attention to these barriers as they relate to family caregiver involvement and
      clinical outcomes should be a priority in future research.

PMID- 29169882
TI  - Reproducibility of Vessel Density, Fractal Dimension, and Foveal Avascular Zone
      Using 7 Different Optical Coherence Tomography Angiography Devices.
AB  - PURPOSE: To evaluate the reproducibility of parafoveal microvascular anatomy of 7
      different optical coherence tomography angiography (OCT-A) devices by comparing
      vessel density (VD), fractal dimension (FD), and foveal avascular zone (FAZ) of
      superficial and deep capillary plexus in healthy volunteers. DESIGN: Reliability
      analysis. METHODS: Consecutive healthy volunteers presenting at the Eye Clinic,
      Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University
      of Milan in the same clinic visit were imaged by 7 different OCT-A devices:
      Optovue RTVue XR Avanti (Optovue, Inc, Fremont, California, USA), prototype
      Spectralis OCT-A (Spectralis; Heidelberg Engineering, Heidelberg, Germany),
      AngioPlex (Cirrus 5000 HD-OCT; Carl Zeiss Meditec, Inc, Dublin, California, USA),
      prototype PlexElite (Carl Zeiss Meditec), RS-3000 Advance (Nidek, Gamagori,
      Japan), OCT-HS100 (Canon, Tokyo, Japan), and Revo NX (Optopol Technology SA,
      Zawiercie, Poland). OCT-A examinations were performed using a 3 * 3 mm volume
      scan pattern centered on the fovea. Mean VD, FD, and FAZ values between the
      instruments were compared. RESULTS: The 7 different devices presented
      measurements with different mean values, with only a limited number of
      comparisons not significantly different between the instruments. Moreover, Bland
      Altman analysis revealed that the limits of agreement for all the comparisons
      were not acceptable. Regression analysis was used in the development of tables to
      compare various devices, despite which large standard errors were found for both
      intercepts and slope conversion values. CONCLUSIONS: Our results suggest that the
      comparison between instruments is nearly impossible and the set of measurements
      from the various instruments are not interchangeable regarding VD, FD, and FAZ
      for both the superficial and deep capillary plexus.

PMID- 29169883
TI  - Pediatric mechanical circulatory support comes of age.

PMID- 29169884
TI  - The "Spiked Helmet" sign - A potential relationship to Takotsubo cardiomyopathy.
AB  - The "Spiked Helmet" sign (SHs), is a recently described electrocardiographic sign
      which is associated with critical illness and with very high risk of impending
      death. Here, we report the SHs in patient with sepsis and a possible diagnosis of
      Takotsubo cardiomyopathy (TC).

PMID- 29169885
TI  - Model performance and variable selection method - A reply to the reader.

PMID- 29169886
TI  - A potential diagnostic pitfall in acute chest pain: Massive pulmonary embolism
      mimicking acute STEMI.
AB  - BACKGROUND: Pulmonary embolism (PE) represents a clinical challenge for
      clinicians because of nonspecific presentations, including dyspnea, chest pain,
      and tachycardia. The immediate 12-lead electrocardiogram (ECG) is commonly used
      to facilitate differential diagnosis of acute chest pain. Although relative rare,
      massive pulmonary embolism could induce ST segment elevation and mimic acute
      myocardial infarction. CASE PRESENTATION: We present a challenging scenario that
      ECG showed ST segment elevation, nevertheless, urgent coronary angiogram revealed
      non-obstructive coronary artery disease. Unfortunately, the patient suffered from
      cardiac arrest and required extracorporeal membrane oxygenation devices. Finally,
      massive pulmonary embolism was diagnosed. CONCLUSION: This case illustrates acute
      PE could mimic ST segment elevation myocardial infarction. ST elevations on ECG
      should be interpreted after considering clinical presentations before making a
      decision.

PMID- 29169887
TI  - Potential pros and cons of the kinect-based real-time audiovisual feedback device
      during in-hospital cardiopulmonary resuscitation.

PMID- 29169888
TI  - Prevalence and treatment of anxiety among emergency department patients with
      pain.

PMID- 29169889
TI  - Transitory effusive-constrictive pericarditis.
AB  - Pericardial effusion of various sizes is a quite common clinical finding, while
      its progression to effusive-constrictive pericarditis occurs in about 1.4-14% of
      cases. Although available evidence on prevalence and prognosis of this rare
      pericardial syndrome is poor, apparently a considerable proportion of patients
      conservatively managed has a spontaneous resolution after several weeks. A 61
      year-old female presented to our emergency department reporting fatigue, effort
      dyspnea and abdominal swelling. The echocardiography showed large pericardial
      effusion with initial hemodynamic impact, so she underwent a pericardiocentesis
      with drainage of 800-850cm3 of exudative fluid, on which diagnostic
      investigations were undertaken: possible viral and bacterial infections, medical
      conditions, iatrogenic causes, neoplastic and connective tissue diseases were all
      excluded. Despite empirical therapy with NSAIDs and colchicine, after about one
      week she had a recurrence of pericardial effusion and progressive development of
      constriction. Echocardiography performed after a few weeks of anti-inflammatory
      therapy showed resolution of constriction and PE, with clinical improvement. If
      progression of pericardial syndromes to a constrictive form is rarely described
      in literature, cases of transitory effusive-constrictive phase are even more
      uncommon, mainly reported during the evolution of pericardial effusion. According
      to the available data, risk of progression to a constrictive form is very low in
      case of idiopathic pericardial effusion. We report a case of large idiopathic
      subacute pericardial effusion, treated with pericardiocentesis and then evolved
      into an effusive-constrictive pericarditis. A prolonged anti-inflammatory
      treatment leads to complete resolution of pericardial syndrome without necessity
      of pericardiectomy.

PMID- 29169891
TI  - Construction of a novel vaccine by conjugating a B-cell epitope of DPP4 to
      peptide IA2(5)-P2-1 to significantly control type 1 diabetes in NOD mice.
AB  - Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective
      destruction of insulin-producing beta cells leads to impaired glucose metabolism
      and its attendant complications. IA2(5)P2-1, a potent immunogenic carrier which
      designed by our laboratory, can induce high titer specific antibodies when carry
      a B cell epitope, such as B cell epitopes of DPP4, xanthine oxidase, and Urate
      transporter protein. In this report, we describe a novel multi-epitope vaccine
      composing a peptide of DPP4, an anti-diabetic B epitope of Insulinoma antigen
      2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock
      protein 60 (HSP60). Immunization with the multi-epitope vaccine in non-obese
      diabetic (NOD) mice successfully induced specific anti-DPP4 antibody, inhibited
      plasma DPP4 activity, and increased serum GLP-1 level. Moreover, this antibody
      titer was correlated with the dose of immunization (20MUg, 100MUg). Inoculation
      of this vaccine in NOD mice significantly control blood glucose level, improved
      glucose excursion and increased insulin level in vivo. Consistent with a lower
      diabetic and insulitis incidence, a induced splenic T cells proliferation and
      tolerance were observed. IFN-gamma secretion reduced and IL-10 increased
      significantly in the D41-IA2(5)-P2-1 treated mice compared to P277 and control
      group due to the potential immunomodulatory effect of the epitope in the vaccine.
      Immunohistochemical analysis and cytometry showed a rebalance of Th1/Th2 in NOD
      mice. Our results demonstrate that this multi-epitope vaccine may serve as a
      promising therapeutic approach for type 1 diabetes.

PMID- 29169890
TI  - Differences between vaccinated and unvaccinated women explain increase in non
      vaccine-type human papillomavirus in unvaccinated women after vaccine
      introduction.
AB  - The aim of this study was to determine whether an observed increase in non
      vaccine-type human papillomavirus (HPV) in unvaccinated women during the first
      eight years after vaccine introduction may be explained by differences in
      demographics or sexual behaviors, instead of type replacement. We analyzed data
      from three cross-sectional surveillance studies of 13-26 year-old women (total N
      = 1180). For women recruited from a health department clinic, older age (OR =
      1.4, 95% CI: 1.2-1.6) and consistent condom use with main partner in the past 3
      months (OR = 11.6, 95% CI: 3.4-40) were associated with being unvaccinated. For
      women recruited from a teen health center African American race (OR = 0.2, 95%
      CI: 0.07-0.7) and having Medicaid health insurance (OR = 0.3, 95% CI: 0.1-0.7)
      were inversely associated with being unvaccinated. The observed increase in non
      vaccine-type HPV prevalence in unvaccinated women may be explained by differences
      between unvaccinated and vaccinated women.

PMID- 29169892
TI  - Immunization effects of a communication intervention to promote preteen HPV
      vaccination in primary care practices.
AB  - OBJECTIVES: HPV vaccination at the recommended ages of 11-12 is highly effective
      yet has stalled well below the goal of 80% of the population. We evaluated a
      statewide practice-based communication intervention (tools: brochures, posters,
      online training for providers and resources for parents, video game for preteens)
      to persuade parents, preteens and providers to vaccinate against HPV. The 9-month
      intervention started May 1, 2015. METHODS: We compared vaccine initiation and
      completion rates over three 9-month periods (baseline, intervention, post
      intervention) between practices enrolled in the intervention and a comparable
      comparison group. All practices reported to the North Carolina Immunization
      Registry (NCIR) and had at least 100 11- and 12-year-olds who had not completed
      the HPV vaccine series. Of 175 eligible practices, the 14 intervention practices
      included 19,398 individuals and the 161 comparison practices included 127,896
      individuals. An extended Cox model was used to test the intervention effect.
      RESULTS: The intervention had a significant effect on both initiation and
      completion during the intervention and post-intervention periods; the estimated
      hazard ratio (HR) for initiation was 1.17 (p = .004) during the intervention and
      1.11 (p = .005) post-intervention. Likewise, completion during the intervention
      period was 17% higher in intervention practices, after controlling for baseline
      differences. This effect increased in the post-intervention period to 30% higher
      (p = .03). CONCLUSIONS: Individuals in the intervention practices were 17% more
      likely to initiate and complete HPV vaccination than in the comparison practices
      during the intervention period and the effect was sustained post-intervention.
      This intervention is promising for increasing rates of HPV vaccination at ages 11
      12.

PMID- 29169894
TI  - Preparing for rotavirus vaccine introduction - A retrospective assessment of the
      epidemiology of intussusception in children below 2 years of age in Nepal.
AB  - BACKGROUND: Rotavirus is the most common cause of severe diarrhea in Nepali
      children, accounting for 25-33% of childhood diarrhea hospitalizations. Two
      rotavirus vaccines recommended for inclusion in national immunization programs
      have been associated with a low risk of intussusception in post-marketing studies
      conducted in several countries. Data on the epidemiology of intussusception
      hospitalizations are lacking in Nepal. Thus, we aimed to describe the
      epidemiology of intussusception-associated hospitalizations among Nepali children
      in preparation for rotavirus vaccine introduction. METHODS: A retrospective
      review of intussusception hospitalizations for a three year period was conducted
      at two major pediatric hospitals in Kathmandu, Nepal. Possible intussusception
      cases were identified through admission, discharge, and operation theater logs
      and ultrasound registers. Cases with a diagnosis of possible intussusception were
      selected for medical record review and classified as confirmed if they met the
      Brighton Collaboration level 1 criteria of diagnostic certainty and the child was
      aged < 24 months. Data on demographics, clinical course, and outcome were
      abstracted and analyzed. RESULTS: Eight-five confirmed intussusception cases were
      identified; most (96%) were confirmed at surgery. The number of intussusception
      cases peaked between ages 4-7 months; no cases occurred in children 0-2 months.
      Fifty-nine (64%) case-patients were male. The median duration of symptoms before
      admission was 2 days (range: 0-14). Abdominal pain, bloody stool, and vomiting
      were the most common clinical features. All cases underwent surgical treatment;
      there was only one death. CONCLUSIONS: This is the first study to evaluate the
      epidemiology of intussusception hospitalizations among children aged < 24 months
      in Nepal. Because the public health impact of rotavirus vaccination could be
      substantial in Nepal, where childhood diarrhea-related morbidity and mortality
      are high, this baseline knowledge of intussusception prior to introduction of
      rotavirus vaccine in the national immunization schedule will provide useful
      information for post-vaccine introduction safety monitoring.

PMID- 29169893
TI  - Potential for a booster dose of rotavirus vaccine to further reduce diarrhea
      mortality.
AB  - Concern has grown that children vaccinated against rotavirus in developing
      countries may be vulnerable to rotavirus diarrhea in the second year of life due
      to waning immunity. Adding a booster dose of rotavirus vaccine at 9 or 12 months
      of age with measles vaccine has been suggested as a strategy to address this. We
      evaluated the hypothetical potential benefits of a booster dose on reduction of
      rotavirus mortality. The projected number of deaths averted were calculated using
      national level full series vaccination coverage, estimated national rotavirus
      deaths by week of age, and VE at <12 months of age and >=12 months of age derived
      from the published literature. We assumed three functional forms of waning based
      on the VE estimates: stepwise, linear, and logarithmic. We modeled three
      potential boosting scenarios: (a) reduced VE waning in the second year of life by
      50%, (b) reestablished second year of life VE to the levels in the first year of
      life, and (c) boosted first year VE by 50% of the difference between VE in the
      first and second years. To express uncertainty resulting from the parameters,
      each of the nine models were run 1000 times using a random sample of input
      values. Across all WHO regions, with the stepwise models we estimated a median of
      9800 (95%CI: 9400, 10,200), 19,600 (95%CI: 18,800, 20,400), and 29,400 (95%CI:
      28,200, 30,700) additional rotavirus deaths averted in the reduced VE waning,
      reestablished VE, and boosted VE scenarios. These estimates were highly sensitive
      to the assumed functional form of waning with approximately 65-80% fewer deaths
      averted if immunity waned in a linear or logarithmic fashion compared to the
      stepwise model. While these projections will benefit from improved input data
      points, our resultsinform consideration of booster doses of rotavirus vaccine.

PMID- 29169895
TI  - Additional features of Gillespie syndrome in two Brazilian siblings with a novel
      ITPR1 homozygous pathogenic variant.
AB  - Gillespie syndrome (GS) [MIM: 206700] is a very rare condition characterized by
      bilateral iris defect, congenital hypotonia, cerebellar ataxia and intellectual
      disability. The typical iris anomaly is considered necessary to the diagnosis of
      GS. Recently, variants in ITPR1 were described causing GS. Non-neurological
      features were reported in few patients. Here we describe two consanguineous
      siblings with GS and a novel homozygous ITPR1 pathogenic variant (p.N984fs). They
      also present a cardiac defect (pulmonary valve stenosis) and one sib had a
      genitourinary malformation (ureteropelvic junction obstruction). Our report
      reinforces ITPR1 as the cause of GS and suggests a possible role of ITPR1 in the
      development of other organs.

PMID- 29169896
TI  - The current place of medical therapy in uterine fibroid management.
AB  - Uterine fibroids (also known as leiomyomas or myomas) are the most common form of
      benign uterine tumors. Current management strategies mainly involve surgical
      interventions, but the choice of treatment is guided by patient's age and desire
      to preserve fertility or avoid "radical" surgery. Surgical and non-surgical
      approaches include hysterectomy myomectomy by hysteroscopy, myomectomy by
      laparotomy or laparoscopy, uterine artery embolization, and magnetic resonance
      guided focused ultrasound surgery. The need for alternatives to surgical
      intervention is very real, especially for women seeking to preserve their
      fertility. There is growing evidence of the crucial role of progesterone pathways
      in the pathophysiology of uterine fibroids, and the efficacy of long-term
      intermittent use of selective progesterone receptor modulators such as ulipristal
      acetate was recently demonstrated by randomized controlled studies.

PMID- 29169897
TI  - Wound healing.
AB  - Wound healing is an important physiological process to maintain the integrity of
      skin after trauma, either by accident or by intent procedure. The normal wound
      healing involves three successive but overlapping phases, including
      hemostasis/inflammatory phase, proliferative phase, and remodeling phase.
      Aberration of wound healing, such as excessive wound healing (hypertrophic scar
      and keloid) or chronic wound (ulcer) impairs the normal physical function. A
      large number of sophisticated experimental studies have provided insights into
      wound healing. This article highlights the information after 2010, and the main
      text includes (i) wound healing; (ii) wound healing in fetus and adult; (iii)
      prostaglandins and wound healing; (iv) the pathogenesis of excessive wound
      healing; (v) the epidemiology of excessive wound healing; (vi) in vitro and in
      vivo studies for excessive wound healing; (vii) stem cell therapy for excessive
      wound healing; and (viii) the prevention strategy for excessive wound healing.

PMID- 29169898
TI  - Hyperemesis gravidarum, pregnancy and bone loss.

PMID- 29169899
TI  - Comparison of optical coherence tomography findings and visual field changes in
      patients with primary open-angle glaucoma and amyotrophic lateral sclerosis.
AB  - Recent studies revealing genetic connection of primary open angle glaucoma (POAG)
      and amyotrophic lateral sclerosis (ALS) have received particular attention.
      Exploring the evidence for common pathogenesis of these two progressive
      neurological disorders may assist in understanding the mechanism and searching
      for new treatment. Retinal nerve fiber layer (RNFL) defect and corresponding
      visual field (VF) impairment are well known neuropathy signs in glaucoma. In our
      study, thickness of certain retinal layer in ALS patients was analyzed to detect
      ganglion cell's soma and axon, and for first time visual field was examined for
      ALS. The correlation of retinal involvement and ALS progression were also
      investigated. The results were compared with those of POAG. The study may provide
      new knowledge for these two neurodegenerative diseases.

PMID- 29169900
TI  - Cardiotonic actions of quercetin and its metabolite tamarixetin through a
      digitalis-like enhancement of Ca2+ transients.
AB  - The plant-derived flavonoid, quercetin (QCT), has many biological actions,
      including cardioprotective actions, resulting from its antioxidant and anti
      inflammatory effects. In this study, effects of QCT and its metabolites on the
      contraction and Ca2+ transients (CaT) of mouse single cardiomyocytes were
      simultaneously measured and compared with those of isoproterenol and digoxin.
      Furthermore, cardiac function and plasma concentrations were analyzed after bolus
      intravenous administration of QCT in mice. QCT and its metabolite, tamarixetin,
      as well as isoproterenol and digoxin, enhanced the contraction and CaT of
      cardiomyocytes. The inotropic action of isoproterenol was accompanied by an
      increase in the velocities of sarcomere shortening and relengthening and CaT
      decay through activation of cAMP-dependent protein kinase; however, no such
      lusitropic effects accompanied the inotropic action of QCT, tamarixetin or
      digoxin. Intravenous administration of QCT to mice resulted in a sustained
      increase in cardiac systolic function; QCT was rapidly metabolized to tamarixetin
      and its plasma concentration was maintained at high levels over a similar time
      frame as the enhancement of cardiac systolic function. These results suggest that
      QCT exerts a cardiotonic action in vivo at least, in part, through digitalis-like
      enhancement of CaT by itself and its metabolite tamarixetin.

PMID- 29169901
TI  - [Transfusion practices in elderly patients: A descriptive study about 241
      patients at the university hospital of Brest].
AB  - : Red blood cell transfusion is commonly required for elderly patients with
      little specific guidelines for this population. We wished to study the
      transfusion practices for patients aged>=75 years transfused with red blood cells
      in all units of our institution. The aim of this work is to describe this
      population of patients and to compare the transfusion practices to the HAS and
      ANSM guidelines published in 2014. METHODS: An observational study was performed
      including patients>=75 years, transfused with red blood cells between 27th
      January to 27th March 2014. Analysis of data included the patients' typology, the
      characteristics of anemia, the indications and transfusion practices, and the
      adequation with the guidelines. RESULTS: Two hundred and forty-one patients were
      transfused during the period with 422 transfusion episodes (mean age 83+/-5.2
      years, sex-ratio women/men 1.4 with 4.4+/-2 pathologies and 6.7+/-3.2
      treatments). Only 4.5% of the patients were transfused in geriatric wards. In 61%
      of the cases, the anemia is acute and chronic in 39%. Fatigue was reported in
      50.6% of the cases and dyspnee in 31.7%. A percentage of 31.1 of the patients
      were prescribed furosemide for transfusion. The mean transfusion recovery was
      1.2+/-0.5g/dL. Two adverse events were reported. Overall, only 10.4% of the
      prescriptions were not compliant with the guidelines of 2014. CONCLUSION: In this
      study, we describe transfusion practices for patients aged>=75 years. Although
      the non-compliance with the guidelines is weak, it is possible to improve the
      transfusion practices taking care of the geriatric characteristics. Prospective
      studies on a larger scale have to be done to converge on a more consensual
      management.

PMID- 29169902
TI  - [Reversion of overweight and obesity in Vilafranca del Penedes child population:
      ACTIVA'T Program (2012)].
AB  - OBJECTIVE: To assess a 6-month nutritional and physical activity intervention
      program on the nutritional status of overweight or obese and not very active 8-14
      years old children by means of a controlled pre-post design (ACTIVA'T program).
      METHOD: Pre-post study in 8-14 years old overweight or obese and low active
      children from Vilafranca del Penedes (Barcelona, Spain) randomized in control
      group (n = 51, 47.1% girls, nutritional intervention and <=3h/wk physical
      activity) and ACTIVA'T group (n = 45, 37.8% girls, nutritional and physical
      activity >=5h/wk intervention). Body mass index, waist/height index, and diet
      quality by means of KIDMED test at the beginning and at the end of the program
      were assessed. During the intervention, each participant was accompanied by a
      relative (father or mother) who performed the same activities as the children.
      RESULTS: Dietary recommendations have positively changed the habits of both
      ACTIVA'T and control group. The reversion in the prevalence of overweight and
      obesity was 93.8% and 58.6%, respectively, in the ACTIVA'T group, compared to
      25.0% and 35.8% in the control group. Abdominal obesity was decreased from 42.2%
      to 17.8% in the ACTIVA'T group and from 47.1% to 27.5% in the control group.
      CONCLUSIONS: The program ACTIVA'T (nutritional education and physical activity
      promotion) improves the quality of diet and reverses the prevalence of overweight
      and obesity in the underactive child population.

PMID- 29169903
TI  - [New public health challenges in vector management: black flies in Murcia
      (Spain)].
AB  - Historically, no black fly (Diptera: Simuliidae) nuisance has been reported in
      the Murcia Region. Back in September 2016 the Ojos City Council has contacted the
      Regional Public Health General Directorate for help regarding a local insect
      nuisance, most probably based on mosquitoes. After sampling with a BG-sentinel 2
      trap, collecting adult specimens with an entomological aspirator, and collect
      larvae and pupae on submerged giant cane stalks at the river, it turned out that
      Simulium sergenti was the insect species causing the nuisance. This species is
      not considered particularly anthropophilic; therefore, a low vector risk for
      human health was considered. However, the high fly density impaired the life
      quality of the people at the village. A management plan was recommended, treating
      the river with Bacillus thuringiensis var israelensis.

PMID- 29169905
TI  - Fully laparoscopic left hepatectomy - a technical reference proposed for standard
      practice compared to the open approach: a retrospective propensity score model.
AB  - BACKGROUND: Laparoscopic left hemihepatectomy (LLH) may be an alternative to open
      (OLH). There are several original variations in the technical aspects of LLH, and
      no accepted standard. The aim of this study is to assess the safety and
      effectiveness of the technique developed at Henri Mondor Hospital since 1996.
      METHODS: The technique of LLH was conceived for safety and training of two mature
      generations of lead surgeons. The technique includes full laparoscopy, ventral
      approach to the common trunk, extrahepatic pedicle dissection, CUSA(r)
      parenchymal transection, division of the left hilar plate laterally to the
      Arantius ligament, and ventral transection of the left hepatic vein. The outcomes
      of LLH and OLH were compared. Perioperative analysis included intra- and
      postoperative, and histology variables. Propensity Score Matching was undertaken
      of background covariates including age, ASA, BMI, fibrosis, steatosis, tumour
      size, and specimen weight. RESULTS: 17 LLH and 51 OLH were performed from 1996 to
      2014 with perioperative mortality rates of 0% and 6%, respectively. In the LLH
      group, two patients underwent conversion to open surgery. Propensity matching
      selected 10 LLH/OLH pairs. The LLH group had a higher proportion of procedures
      for benign disease. LLH was associated with longer operating time and less blood
      loss. Perioperative complications occurred in 30% (LLH) and 10% (OLH) (p = 1).
      Mortality and ITU stay were similar. CONCLUSION: This technique is recommended as
      a possible technical reference for standard LLH.

PMID- 29169904
TI  - Outcomes after vascular resection during curative-intent resection for hilar
      cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary
      malignancy consortium.
AB  - BACKGROUND: Surgical resection is the cornerstone of curative-intent therapy for
      patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR)
      in the treatment of HC in western centres is not well defined. METHODS: Utilizing
      data from the U.S. Extrahepatic Biliary Malignancy Consortium, patients were
      grouped into those who underwent resection for HC based on VR status: no VR,
      portal vein resection (PVR), or hepatic artery resection (HAR). Perioperative and
      long-term survival outcomes were analyzed. RESULTS: Between 1998 and 2015, 201
      patients underwent resection for HC, of which 31 (15%) underwent VR: 19 patients
      (9%) underwent PVR alone and 12 patients (6%) underwent HAR either with (n = 2)
      or without PVR (n = 10). Patients selected for VR tended to be younger with
      higher stage disease. Rates of postoperative complications and 30-day mortality
      were similar when stratified by vascular resection status. On multivariate
      analysis, receipt of PVR or HAR did not significantly affect OS or RFS.
      CONCLUSION: In a modern, multi-institutional cohort of patients undergoing
      curative-intent resection for HC, VR appears to be a safe procedure in a highly
      selected subset, although long-term survival outcomes appear equivalent. VR
      should be considered only in select patients based on tumor and patient
      characteristics.

PMID- 29169906
TI  - Limits on normal cochlear 'third' windows provided by previous investigations of
      additional sound paths into and out of the cat inner ear.
AB  - While most models of cochlear function assume the presence of only two windows
      into the mammalian cochlea (the oval and round windows), a position that is
      generally supported by several lines of data, there is evidence for additional
      sound paths into and out of the inner ear in normal mammals. In this report we
      review the existing evidence for and against the 'two-window' hypothesis. We then
      determine how existing data and inner-ear anatomy restrict transmission of sound
      through these additional sound pathways in cat by utilizing a well-tested model
      of the cat inner ear, together with anatomical descriptions of the cat cochlear
      and vestibular aqueducts (potential additional windows to the cochlea). We
      conclude: (1) The existing data place limits on the size of the cochlear and
      vestibular aqueducts in cat and are consistent with small volume-velocities
      through these ducts during ossicular stimulation of the cochlea, (2) the
      predicted volume velocities produced by aqueducts with diameters half the size of
      the bony diameters match the functional data within +/-10 dB, and (3) these
      additional volume velocity paths contribute to the inner ear's response to non
      acoustic stimulation and conductive pathology.

PMID- 29169907
TI  - Upside-down position for the out of hospital management of children with
      supraventricular tachycardia.
AB  - BACKGROUND: The upside-down position is a little known modified Valsalva
      manoeuvre (VM). The aim of this study was to investigate the safety and the
      efficacy of the upside-down position for the treatment of paroxysmal SVT in
      children. METHODS: Twenty-four paediatric patients followed for SVT were
      enrolled. The patients were assigned (1:1) to a standard VM or to an upside-down
      position at the first episode of SVT at home. If no cardioversion occurred, a
      second attempt was undertaken with the other VM. At the patient's first relapse,
      the intervention protocol was applied in the opposite order at home. RESULTS: The
      upside-down position compared to standard VM reached 67% vs 33% rate of
      cardioversion at a first attempt, followed by 50% vs 0% rate of cardioversion in
      patients who had failed the first attempt. After having reversed the order of
      intervention in case of SVT recurrence, we recorded 67% vs 25% and 71% vs 42%
      success rates in favour of the upside-down position. There were no adverse
      events. CONCLUSION: The upside-down position was safe and tended to be more
      effective than standard VM for out of hospital SVT treatment. Doctors and parents
      should be more aware of this effective but overlooked manoeuvre.

PMID- 29169908
TI  - Increased risk and severity of unprovoked venous thromboembolism with clustering
      cardiovascular risk factors for atherosclerosis: Results of the REMOTEV registry.
AB  - BACKGROUND: The role of cardiovascular risk factors (CVRF) for atherosclerosis in
      venous thromboembolic disease (VTE) is controversial. The aim of this study was
      to evaluate the impact of CVRF and their cumulative effects on the occurrence of
      unprovoked VTE, severity, recurrence and survival. METHODS AND RESULTS: This is a
      prospective cohort from the REMOTEV registry including all consecutively
      hospitalized patients for acute symptomatic VTE. From November 2013 to December
      2016, 515 patients with 6months follow-up (FU) were selected for the analysis.
      Events were classified as unprovoked or provoked VTE. In univariate analysis,
      hypertension (OR 1.44, [95% CI 1.01-2.06]), diabetes (OR 2.07, [95% CI: 1.25
      3.55]) and age (OR 1.94, [95% CI: 1.31-2.88]) were significantly associated with
      the risk of unprovoked VTE. After adjustment, diabetes (OR 1.82, [95% CI: 1.07
      3.18]) and age (OR 1.79, [95% CI: 1.15-2.8]) remained associated with the risk of
      unprovoked VTE. The proportion of unprovoked VTE increased significantly with the
      number of CVRF adjusted for thrombophilia (1 CVRF: OR 3 [95% CI: 1.44-6.52]) 2
      CVRF: OR 4.33 [95% CI: 2.07-9.49] and >=3 CVRF: OR 4.58 [95% CI: 2.27-9.7]). The
      severity of pulmonary embolism was significantly associated with CVRF clustering.
      There were more VTE recurrences and deaths during the 6months of FU with
      cumulative CVRF. CONCLUSION: The risks of unprovoked VTE and PE severity are
      associated with clustering CVRF. The role of cumulative CVRF predominates rather
      than the specific burden of each of the CVRF in the risk of VTE occurrence.

PMID- 29169909
TI  - Ethyl pyruvate attenuates myocardial ischemia-reperfusion injury exacerbated by
      hyperglycemia via retained inhibitory effect on HMGB1.
AB  - BACKGROUND: Hyperglycemia (HG) exacerbates myocardial ischemia/reperfusion (I/R)
      injury and renders protective strategies ineffective by amplified inflammatory
      response via enhanced high-mobility group box-1 (HMGB1) release. This study
      investigated the role of ethyl pyruvate (EP) against myocardial I/R injury under
      a clinically relevant HG condition. METHODS: Sprague-Dawley rats (n=76) were
      randomly assigned to 6 groups: normoglycemia (NG)-Sham, NG-I/R-control (C,
      saline), NG-I/R-EP treatment (50mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and
      HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2g/kg dextrose. I/R was
      induced by ligation of the left anterior descending artery for 30min followed by
      4h of reperfusion. RESULTS: HG resulted in exacerbation of myocardial infarct
      size by 19% with amplified activation of HMGB1-receptors of advanced glycation
      end products/toll like receptors-NF-kappaB pathway compared to NG following I/R,
      which all could be attenuated by EP. EP treatment was associated with diminished
      tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 expressions. It
      also served to normalize the increase in pro-apoptotic Bax and the decrease in
      anti-apoptotic Bcl-2 protein levels. These effects were associated with decreased
      myocardial apoptosis and infarct size (by 30% and 36% in the NG and HG groups,
      respectively) regardless of the glycemic condition. CONCLUSION: HG exacerbated
      myocardial I/R injury through amplified inflammatory response via increased HMGB1
      level. EP treatment upon reperfusion conveyed significant myocardial protection
      against the I/R injury under both NG and HG conditions. Common to both glycemic
      conditions, associated mechanisms involved attenuated increase in HMGB1 level and
      suppression of its down-stream pathways.

PMID- 29169910
TI  - The effect of the number and level of emergency medical technicians on patient
      outcomes following out of hospital cardiac arrest in Taipei.
AB  - AIM: The effect of the number and level of on-scene emergency medical technicians
      (EMTs) on the outcomes of patients with out-of-hospital cardiac arrest (OHCA)
      remains unclear. We aimed to test the association between the number and level of
      EMTs and the outcomes of patients with OHCA. METHODS: We analysed Utstein-based
      registry data on OHCA in Taipei from 2011 to 2015. The eligible patients were
      adults, aged >=20 years, with non-traumatic OHCA who underwent resuscitation
      attempts. The exposures were the total number of EMTs or the EMT-Paramedic (EMT
      P) ratio >50%. The outcome of interest was survival to discharge. RESULTS: During
      study period, total 8262 OHCA cases were included, of which 1085 (13.1%) were
      approached by crews with an EMT-P ratio >50%. While an increase in the number of
      EMTs on-scene was not associated with better chances of survival (adjusted odds
      ratio [aOR] 0.98, 95% confidence interval [CI] 0.89-1.08), an EMT-P ratio >50%
      was significantly associated with improved outcome (aOR 1.36, 95% CI 1.06-1.76).
      Subgroup analyses showed that EMT-P >50% significantly benefited survival in
      witnessed OHCA cases with non-shockable rhythm (aOR 1.69, 95% CI 1.01-2.58).
      Survival was the highest among cases seen by four EMTs with an EMT-P ratio >50%
      (aOR 2.54, 95% CI 1.43-4.50). CONCLUSION: An on-scene EMT-P ratio >50% was
      associated with improved survival to discharge of OHCA cases, especially in those
      with witnessed, non-shockable rhythm. The presence of four EMTs with an EMT-P
      ratio >50% at the scene of OHCA was associated with the best outcome.

PMID- 29169911
TI  - Optimizing chest x-rays in patients treated with the LUCAS chest compression
      system.

PMID- 29169912
TI  - Comparison of the Between the Flags calling criteria to the MEWS, NEWS and the
      electronic Cardiac Arrest Risk Triage (eCART) score for the identification of
      deteriorating ward patients.
AB  - INTRODUCTION: Traditionally, paper based observation charts have been used to
      identify deteriorating patients, with emerging recent electronic medical records
      allowing electronic algorithms to risk stratify and help direct the response to
      deterioration. OBJECTIVE(S): We sought to compare the Between the Flags (BTF)
      calling criteria to the Modified Early Warning Score (MEWS), National Early
      Warning Score (NEWS) and electronic Cardiac Arrest Risk Triage (eCART) score.
      DESIGN AND PARTICIPANTS: Multicenter retrospective analysis of electronic health
      record data from all patients admitted to five US hospitals from November 2008
      August 2013. MAIN OUTCOME MEASURES: Cardiac arrest, ICU transfer or death within
      24h of a score RESULTS: Overall accuracy was highest for eCART, with an AUC of
      0.801 (95% CI 0.799-0.802), followed by NEWS, MEWS and BTF respectively (0.718
      [0.716-0.720]; 0.698 [0.696-0.700]; 0.663 [0.661-0.664]). BTF criteria had a high
      risk (Red Zone) specificity of 95.0% and a moderate risk (Yellow Zone)
      specificity of 27.5%, which corresponded to MEWS thresholds of >=4 and >=2, NEWS
      thresholds of >=5 and >=2, and eCART thresholds of >=12 and >=4, respectively. At
      those thresholds, eCART caught 22 more adverse events per 10,000 patients than
      BTF using the moderate risk criteria and 13 more using high risk criteria, while
      MEWS and NEWS identified the same or fewer. CONCLUSION(S): An electronically
      generated eCART score was more accurate than commonly used paper based
      observation tools for predicting the composite outcome of in-hospital cardiac
      arrest, ICU transfer and death within 24h of observation. The outcomes of this
      analysis lend weight for a move towards an algorithm based electronic risk
      identification tool for deteriorating patients to ensure earlier detection and
      prevent adverse events in the hospital.

PMID- 29169913
TI  - The strategic function of the P5-ATPase ATP13A2 in toxic waste disposal.
AB  - The P-type ATPase ATP13A2 protein was originally associated with a form of
      Parkinson's Disease (PD) known as Kufor Rakeb Syndrome (KRS). However, in the
      last years it has been found to underlay variants of neuronal ceroid
      lipofuscinoses and hereditary spastic paraplegia. These findings expand the
      clinical and genetic spectrum of ATP13A2-associated disorders, which are commonly
      characterized by lysosomal dysfunction. Nowadays it is well known that lysosomes
      are not merely related to the degradation and recycling of cellular waste, but
      are also involved in fundamental processes such as secretion, plasma membrane
      repair, signaling, energy metabolism and autophagy. The essential role of
      lysosomes in these cellular processes has significant implications for health and
      disease. ATP13A2 is localized in lysosomes and late endosomes and its mutation
      leads to lysosome dysfunction, diminishes the exosome secretion and impairs
      autophagic flux. In this review, we first describe ATP13A2-associated disorders
      and their relation with the endolysosomal pathway. We then describe the ATP13A2
      involvement in iron homeostasis and its potential linkage with new pathologies
      like cancer, and finally, we consider the putative role of ATP13A2 in lipid
      processing and degradation, opening the interesting possibility of a broader role
      of this protein providing protection against a variety of disease-associated
      changes affecting cellular homeostasis.

PMID- 29169914
TI  - Low incidence of precore W28* mutant variants in treated hepatitis B virus and
      human immunodeficiency virus co-infected patients.
AB  - The precore (pc) W28* mutation arises from immune-selective pressures during the
      hepatitis B "e" antigen (HBeAg)-positive phase of chronic hepatitis B virus (HBV)
      infection and has been linked to severe liver-related morbidity. Here, we
      examined the determinants of harboring this mutation and its rate of emergence in
      treated patients co-infected with human immunodeficiency virus (HIV) and HBV. In
      a three-year prospective cohort of 165 HIV-HBV co-infected patients, pcW28*
      mutation was determined via DNA-chip during yearly sampling. In a subgroup with
      liver biopsies, HBV covalently-closed circular (ccc)-DNA and total intrahepatic
      (IH)-DNA were quantified by real-time PCR. From respective inclusion to year-3
      visits, median HBV-DNA levels decreased (5.88 log10 IU/mL to <1.78 log10 IU/mL, p
      < 0.001) and tenofovir-use increased (15.8%-71.4%, p < 0.001). At baseline, 47 of
      162 (29.0%) patients had the pcW28* mutation and were more frequently HBeAg
      negative (adjusted-OR = 4.37, 95%CI = 1.76-10.86) and had non-A HBV genotypes
      (adjusted-OR = 9.14, 95%CI = 4.05-20.66). No association with HIV-related factors
      was observed. In 114 patients without baseline mutation and available data, four
      developed incident pcW28* mutation by the end of follow-up (cumulative 3.5%,
      95%CI = 1.3-9.1%). In the 32 patients with liver biopsies, 10 (31.3%) patients
      harboring the pcW28* mutation had significantly lower adjusted mean cccDNA (0.05
      versus without = 0.43 copies/cell, p < 0.001) and total IH-DNA levels (2.31
      versus without = 18.59 copies/cell, p = 0.006). In conclusion, the pcW28*
      mutation infrequently appeared in this co-infected study population with
      increased use of potent antivirals and suppressed levels of circulating virus.

PMID- 29169915
TI  - The influence of ketogenic diets on mood stability in bipolar disorder.

PMID- 29169916
TI  - Comparative performance of lissamine green stains.
AB  - PURPOSE: To investigate the performance of lissamine green strips from different
      manufacturers. Additionally, the repeatability, need for sequential dye
      instillation and impact of repeated lid evertion on lid wiper staining were
      assessed. METHODS: Study 1 was a prospective, randomised cross-over study where
      controlled volumes of lissamine green solution prepared from strips (Biotech,
      Lissaver, GreenGlo, OPGreen) were instilled (right eye: single; left eye: double
      instillation) on five different days, with OPGreen being tested twice. Lids were
      everted and digital photographs taken, which were later assessed by a masked
      observer. Study 2 was an investigator-masked, randomised, controlled study
      testing the impact of single versus repeated lid evertion. Lid wiper staining was
      graded (0 to 3 in 0.5 steps). RESULTS: Lid wiper staining differed significantly
      between lissamine green solutions, with GreenGlo showing the highest amount of
      staining, and Lissaver the least (all p>0.009). There were no differences in lid
      wiper staining over two days, using the OPGreen solution (all p>0.05). The number
      of drops instilled (single versus double) did not significantly affect lid wiper
      staining (all p>0.05). Repeated lid evertion increased lid wiper staining
      (p=0.007 when combined with double drop instillation). Light absorbance patterns
      and measured concentrations aligned with clinical findings. CONCLUSION: There
      were significant differences in performance between lissamine green solutions.
      Lid wiper staining was impacted by repeated lid evertion but sequential
      instillation and use of the Korb grading scale provided little advantage over
      simpler methods Clinicians must consider this when investigating lid wipers,
      especially when interpreting a negative finding.

PMID- 29169917
TI  - Primary Cutaneous Blastomycosis After Inoculation From A Woodworking Blade.

PMID- 29169918
TI  - The Use of Body Habitus Reference Images Improves the Ability of Novices to
      Accurately Estimate Children's Weight Using the PAWPER XL Tape System.
AB  - BACKGROUND: The original methodology of the PAWPER (Pediatric Advanced Weight
      Prediction in the Emergency Room) tape relies on a gestalt visual assessment of a
      child's body habitus to adjust a length-based weight estimation. This assessment
      is dependent on the user's subjective opinion, which may result in aberrations in
      accuracy between users and populations. With the development of the second
      generation PAWPER XL tape, a more objective method of habitus evaluation was
      desired. OBJECTIVE: The aim of this study was to evaluate a new, more objective
      figural reference image system and a new checklist system for quantifying body
      habitus. METHODS: Volunteers were asked to assess the body habitus score of 90
      children from a sequence of photographic images using the standard gestalt visual
      assessment system, a new checklist system, and a system using figural reference
      images. PAWPER XL tape weight estimations were generated from these scores, which
      were compared between the three test groups. Participants were also surveyed on
      their preferences for the different methodologies. RESULTS: There were 11,505
      habitus score assessments from 138 doctor, nurse, and paramedic participants. The
      figural reference image system significantly outperformed the checklist system
      and the gestalt visual assessment system in terms of weight estimation accuracy,
      achieving 70.9%, 61.1%, and 60.9% of estimations within 10% of measured weight,
      respectively. The participants expressed a strong subjective preference for the
      image system because of speed of use, ease of use, perceived accuracy,
      objectivity, and low cognitive load. CONCLUSIONS: The figural reference image
      system was objectively much more accurate than, and subjectively preferable to,
      the original gestalt visual estimation methodology.

PMID- 29169919
TI  - Harnessing the native type I-B CRISPR-Cas for genome editing in a polyploid
      archaeon.
AB  - Research on CRISPR-Cas (clustered regularly interspaced short palindromic repeats
      CRISPR associated protein) systems has led to the revolutionary CRISPR/Cas9
      genome editing technique. However, for most archaea and half of bacteria,
      exploitation of their native CRISPR-Cas machineries may be more straightforward
      and convenient. In this study, we harnessed the native type I-B CRISPR-Cas system
      for precise genome editing in the polyploid haloarchaeon Haloarcula hispanica.
      After testing different designs, the editing tool was optimized to be a single
      plasmid that carries both the self-targeting mini-CRISPR and a 600-800 bp donor.
      Significantly, chromosomal modifications, such as gene deletion, gene tagging or
      single nucleotide substitution, were precisely introduced into the vast majority
      of the transformants. Moreover, we showed that simultaneous editing of two
      genomic loci could also be readily achieved by one step. In summary, our data
      demonstrate that the haloarchaeal CRISPR-Cas system can be harnessed for genome
      editing in this polyploid archaeon, and highlight the convenience and efficiency
      of the native CRISPR-based genome editing strategy.

PMID- 29169920
TI  - A glycolysis-based ten-gene signature correlates with the clinical outcome,
      molecular subtype and IDH1 mutation in glioblastoma.
AB  - Reprogrammed metabolism is a hallmark of cancer. Glioblastoma (GBM) tumor cells
      predominantly utilize aerobic glycolysis for the biogenesis of energy and
      intermediate nutrients. However, in GBM, the clinical significance of glycolysis
      and its underlying relations with the molecular features such as IDH1 mutation
      and subtype have not been elucidated yet. Herein, based on glioma datasets
      including TCGA (The Cancer Genome Atlas), REMBRANDT (Repository for Molecular
      Brain Neoplasia Data) and GSE16011, we established a glycolytic gene expression
      signature score (GGESS) by incorporating ten glycolytic genes. Then we performed
      survival analyses and investigated the correlations between GGESS and IDH1
      mutation as well as the molecular subtypes in GBMs. The results showed that GGESS
      independently predicted unfavorable prognosis and poor response to chemotherapy
      of GBM patients. Notably, GGESS was high in GBMs of mesenchymal subtype but low
      in IDH1-mutant GBMs. Furthermore, we found that the promoter regions of tumor
      promoting glycolytic genes were hypermethylated in IDH1-mutant GBMs. Finally, we
      found that high GGESS also predicted poor prognosis and poor response to
      chemotherapy when investigating IDH1-wildtype GBM patients only. Collectively,
      glycolysis represented by GGESS predicts unfavorable clinical outcome of GBM
      patients and is closely associated with mesenchymal subtype and IDH1 mutation in
      GBMs.

PMID- 29169921
TI  - Cotton functional genomics reveals global insight into genome evolution and fiber
      development.
AB  - Due to the economic value of natural textile fiber, cotton has attracted much
      research attention, which has led to the publication of two diploid genomes and
      two tetraploid genomes. These big data facilitate functional genomic study in
      cotton, and allow researchers to investigate cotton genome structure, gene
      expression, and protein function on the global scale using high-throughput
      methods. In this review, we summarized recent studies of cotton genomes.
      Population genomic analyses revealed the domestication history of cultivated
      upland cotton and the roles of transposable elements in cotton genome evolution.
      Alternative splicing of cotton transcriptomes was evaluated genome-widely.
      Several important gene families like MYC, NAC, Sus and GhPLDalpha1 were
      systematically identified and classified based on genetic structure and
      biological function. High-throughput proteomics also unraveled the key functional
      proteins correlated with fiber development. Functional genomic studies have
      provided unprecedented insights into global-scale methods for cotton research.

PMID- 29169922
TI  - Site-specific transfer of chromosomal segments and genes in wheat engineered
      chromosomes.
AB  - Recently, engineered minichromosomes have been produced using a telomere-mediated
      truncation technique in some plants. However, the study on transferring genes to
      minichromosomes is very limited. Here, telomere-mediated truncation was
      successfully performed in common wheat (Triticum aestivum) to generate stable
      truncated chromosomes accompanied by a relatively high frequency of chromosomal
      rearrangements. After the cross between transgenic parents, a promoter-less DsRed
      gene in a chromosome from one parent was transferred to another chromosome from
      the other parent at the site behind a maize ubiquitin promoter via the Cre/lox
      system. DsRed transcripts and red fluorescent proteins were detected in the
      recombinant plants. In one such seedling, transgenic signals were detected at the
      centric terminus of chromosome 4D and the distal terminus of chromosome 3A. Clear
      translocations could be detected at the transgenic loci of these two chromosomes.
      Intriguingly, signals of centric-specific sequences were co-localized with the
      translocated D-group chromosomal segment in the terminal region of chromosome 3A.
      Our results indicate that the Cre/lox system induces the gene swapping to the
      target chromosome and non-homologous chromosomal recombination simultaneously.
      These approaches could offer a platform to transfer large DNA fragments or even
      terminal chromosomal segments to other chromosomes of the natural genome.

PMID- 29169923
TI  - Ataxin-10 is involved in Golgi membrane dynamics.

PMID- 29169924
TI  - Short body length phenotype is compensated by the upregulation of nidogen family
      members in a deleterious nid1a mutation of zebrafish.

PMID- 29169925
TI  - Heat stress incidence and matchplay characteristics in Women's Grand Slam Tennis.
AB  - OBJECTIVES: To explore the relationship of wet bulb globe temperature (WBGT) on
      heat-related incidents and alterations in matchplay and behavioural
      characteristics in women's tennis at the Australian Open. DESIGN: From 360 main
      draw Australian Open women's matches (2014-2016), data describing on-court calls
      for trainers, doctors, cooling devices and water, post match medical consults and
      matchplay characteristics were collated. METHODS: Data were referenced against
      estimated WBGT and categorised into standard zones (zone 5: >32.3 degrees C, zone
      4: 30.1-32.2 degrees C, zone 3: 27.9-30 degrees C, zone 2: 22.3-27.9 degrees C,
      zone 1: <22.2 degrees C). Generalized linear models assessed the association of
      WBGT zone on heat-related medical incidences, court call-outs and match
      characteristics. RESULTS: With an increased estimated WBGT zone, there was an
      increase in total trainer calls (+19.5%/zone; p=0.019), total doctor calls
      (+54.1%; p<0.001), total calls for heat related incidents (+55.9%; p<0.001), and
      cooling devices (+31.4%; p<0.001) calculated from the regression slope. When
      match characteristics were adjusted for match quality, significant decreases
      (p<0.001) in the number of winners and net approaches and increase in double
      faults were associated with increased estimated WBGT zone. CONCLUSIONS: An
      association between higher estimated WBGT and medical callouts (heat and non-heat
      related) was evident, with an increased call rate >32 degrees C WBGT, despite no
      heat-related retirements. As estimated WBGT increased, the number of winners and
      net approaches were reduced, while double faults increased, particularly >30
      degrees C WBGT. Accordingly, the manner in which female players manage and play
      in the heat during women's Grand Slam tennis appears to change at ~30 degrees C
      WBGT.

PMID- 29169926
TI  - Association of sleep apnoea syndrome and autonomic neuropathy in type 1 diabetes.

PMID- 29169927
TI  - Metabolic syndrome and impaired glucose metabolism during early postpartum after
      twin pregnancies complicated by gestational diabetes mellitus: Is the risk
      comparable to singleton pregnancies?

PMID- 29169928
TI  - Early involvement of the supinator muscle in Duchenne muscular dystrophy.

PMID- 29169929
TI  - Compound heterozygous RYR1 mutations in a preterm with arthrogryposis multiplex
      congenita and prenatal CNS bleeding.
AB  - RYR1 mutations, the most common cause of non-dystrophic neuromuscular disorders,
      are associated with the malignant hyperthermia susceptibility (MHS) trait as well
      as congenital myopathies with widely variable clinical and histopathological
      manifestations. Recently, bleeding anomalies have been reported in association
      with certain RYR1 mutations. Here we report a preterm infant born at 32 weeks
      gestation with arthrogryposis multiplex congenita due to compound heterozygous,
      previously MHS-associated RYR1 mutations, with additional signs of prenatal
      hemorrhage. The patient presented at birth with multiple joint contractures,
      scoliosis, severe thoracic rigidity and respiratory failure. He continued to
      depend on mechanical ventilation and tube feeding. Muscle histopathology showed a
      marked myopathic pattern with eccentric cores. Interestingly, the patient had
      additional unusual prenatal intraventricular hemorrhage, resulting in post
      hemorrhagic hydrocephalus as well as epidural hemorrhage affecting the spinal
      cord. This report adds to the phenotypic variability associated with RYR1
      mutations, and highlights possible bleeding complications in affected
      individuals.

PMID- 29169930
TI  - Breast Lesion Excision System in the diagnosis and treatment of intraductal
      papillomas - A feasibility study.
AB  - OBJECTIVES: This study aims to evaluate the feasibility of Breast Lesion Excision
      System (BLES) in the treatment of intraductal papillomas. MATERIAL AND METHODS:
      All patients with a needle biopsy -based suspicion of an intraductal papilloma
      who consequently underwent a BLES procedure at Helsinki University Hospital
      between 2011 and 2016 were included in this retrospective study. The purpose of
      the BLES procedure was either to excise the entire lesion or in few cases to
      achieve better sampling. RESULTS: In total, 74 patients underwent 80 BLES
      procedures. Pathological diagnosis after the BLES biopsy confirmed an intraductal
      papilloma without atypia in 43 lesions, whereas 10 lesions were upgraded to high
      risk lesions (HRL) with either atypical ductal hyperplasia or lobular carcinoma
      in situ. Five cases were upgraded to malignancy, two were invasive ductal
      carcinomas and three were ductal carcinoma in situ. Additionally, 18 lesions were
      diagnosed as other benign lesions. Four procedures failed. Complete excision with
      BLES was achieved in 19 out of 43 intraductal papillomas, 6 out of 10 HRL and two
      out of five malignant lesions. No major complications occurred. The BLES
      procedure was adequate in the management of the 71 breast lesions. CONCLUSION:
      The BLES procedure is an acceptable method for the management of small benign and
      high-risk breast lesions such as intraductal papillomas in selected patients.
      Thus, a great amount of diagnostic surgical biopsies can be avoided.

PMID- 29169931
TI  - Aggressive differentiated thyroid cancer.
AB  - Differentiated thyroid cancer is characteristically associated with an innocuous
      clinical course, but a minority of cases may manifest surprisingly aggressive
      behaviour. Such aggressive DTC are directly responsible for the majority of
      thyroid cancer related deaths. Moreover, they contribute indirectly to increased
      DTC-related morbidity, because our inability to differentiate these tumours from
      innocuous DTC at an early stage fuels a significant degree of DTC overtreatment
      around the globe. In the present paper we describe how improved understanding of
      the clinicopathological thyroid tumour progression model and optimization of
      clinical staging systems continues to improve our ability to diagnose and treat
      aggressive DTC. Early recognition of aggressive DTC allows instillation of an
      aggressive management strategy which is based upon surgical-oncologic
      completeness, and minimization of treatment-related sequelae through continued
      development of reconstructive options and focussed delivery of adjuvant
      treatments.

PMID- 29169932
TI  - Active Surveillance Offers Functional Advantages Without Impacting Survival for
      Low-risk Prostate Cancer.

PMID- 29169933
TI  - Cleaning and disinfection in home care: A comparison of 2 commercial products
      with potentially different consequences for respiratory health.
AB  - BACKGROUND: Home care aides perform personal care and homemaking services in
      client homes, including cleaning and disinfection (C&D). Although C&D are
      performed to remove soil and dust, they are increasingly performed for infection
      prevention. Many C&D products contain respiratory irritants. The objective of
      this study was to evaluate 2 commercial products for C&D effectiveness on common
      household surfaces in seniors' homes. METHODS: Two C&D visits were conducted in
      46 seniors' homes. One visit applied a bleach-containing cleaning product and the
      other applied an environmentally preferable product. Before and after C&D, the
      study team performed organic soil bioluminometer measurements on surfaces and
      collected cotton swab and wipe samples for total bacteria count, Staphylococcus
      aureus, and Clostridium difficile identification. RESULTS: Both products removed
      microorganisms from tested surfaces. S aureus was found in 7 households, 1 strain
      of which was methicillin-resistant. Both products removed S aureus from all
      surfaces. Bleach-containing products removed somewhat more soil than
      environmentally preferable products, although results were statistically
      significant for only 1 surface. CONCLUSIONS: The study showed similar, not
      identical, C&D performance for 2 cleaning products with potentially different
      consequences for respiratory health. Additional research is needed to develop
      robust recommendations for safe, effective C&D in home care.

PMID- 29169934
TI  - Sustained reduction in rates of hospital-onset Clostridium difficile infection
      using an automated electronic health record protocol.
AB  - BACKGROUND: An automated protocol was designed within our electronic medical
      record (EMR) to help curb the Clostridium difficile problem at our institution.
      The protocol will identify patients at high risk for C difficile, improve the
      timing of testing of patients infected on admission, and enhance the
      appropriateness of C difficile testing throughout the patient's hospitalization.
      METHODS: Admitted patients with 2 of the following 3 criteria were labeled as
      high risk for C difficile: admission to a medical institution in the preceding 90
      days, administration of antibiotics in the preceding 90 days, or a history of C
      difficile. High-risk patients with diarrhea in the first 3 days of admission are
      identified in the EMR, and prompt testing for C difficile is done. After day 3,
      if diarrhea develops, a series of questions is presented to help test the
      appropriate patients for C difficile. RESULTS: A statistically significant
      reduction in rates of hospital-onset C difficile was achieved after
      implementation of the protocol. CONCLUSIONS: Implementation of an automated
      protocol for targeted testing of high-risk patients for C difficile was
      successful at reducing rates of hospital-onset C difficile by improving timing
      and appropriateness of testing.

PMID- 29169935
TI  - Survey to explore understanding of the principles of aseptic technique:
      Qualitative content analysis with descriptive analysis of confidence and
      training.
AB  - BACKGROUND: In many countries, aseptic procedures are undertaken by nurses in the
      general ward setting, but variation in practice has been reported, and evidence
      indicates that the principles underpinning aseptic technique are not well
      understood. METHODS: A survey was conducted, employing a brief, purpose-designed,
      self-reported questionnaire. RESULTS: The response rate was 72%. Of those
      responding, 65% of nurses described aseptic technique in terms of the procedure
      used to undertake it, and 46% understood the principles of asepsis. The related
      concepts of cleanliness and sterilization were frequently confused with one
      another. Additionally, 72% reported that they not had received training for at
      least 5 years; 92% were confident of their ability to apply aseptic technique;
      and 90% reported that they had not been reassessed since their initial training.
      Qualitative analysis confirmed a lack of clarity about the meaning of aseptic
      technique. CONCLUSION: Nurses' understanding of aseptic technique and the
      concepts of sterility and cleanliness is inadequate, a finding in line with
      results of previous studies. This knowledge gap potentially places patients at
      risk. Nurses' understanding of the principles of asepsis could be improved.
      Further studies should establish the generalizability of the study findings.
      Possible improvements include renewed emphasis during initial nurse education,
      greater opportunity for updating knowledge and skills post-qualification, and
      audit of practice.

PMID- 29169937
TI  - Positive deviance and hand hygiene of nurses in a Quebec hospital: What can we
      learn from the best?
AB  - BACKGROUND: Although it is well known that hand hygiene is the most effective
      measure to prevent health care-associated infections, hand hygiene adherence is
      low in Quebec, as it is elsewhere. For this study, an innovative framework was
      used to explore the clinical practice of nurses regarding hand hygiene and the
      factors that influence it: positive deviance, or the idea that there are people
      who find better solutions to problems than their peers. This study investigated
      positive deviance at the level of the care team to shed light on group dynamics.
      METHODS: We conducted focused ethnographies on 2 care units-a medical-surgery
      unit and a palliative care unit-at a Montreal university hospital. Data
      collection consisted mainly of systematic observations and individual interviews
      with nurses. RESULTS: The results show that positive deviance related to hand
      hygiene is instigated by social cohesion within a care team, created, in this
      study, by the mobilizing leadership of the head nurse in the medical-surgery unit
      and the prevailing humanist philosophy in the palliative care unit. CONCLUSIONS:
      In health care, it can be useful to apply the positive deviance approach to care
      teams instead of individuals to better understand the ideologic and structural
      differences linked to better hand hygiene performance by the nurses.

PMID- 29169936
TI  - Screening for Clostridium difficile colonization on admission to a hematopoietic
      stem cell transplant unit may reduce hospital-acquired C difficile infection.
AB  - Clostridium difficile infection rates are higher in patients undergoing
      hematopoietic stem cell transplants. In our study, patients undergoing
      hematopoietic stem cell transplants or chemotherapy were screened for C difficile
      colonization at admission and placed on contact precautions if they were
      positive. Patient's colonized with C difficile contribute to the overall burden
      of C difficile infection in hospitals.

PMID- 29169938
TI  - Correlation between hospital-level antibiotic consumption and incident health
      care facility-onset Clostridium difficile infection.
AB  - BACKGROUND: The purpose of this single-center, ecologic study is to characterize
      the relationship between facility-wide (FacWide) antibiotic consumption and
      incident health care facility-onset Clostridium difficile infection (HO-CDI).
      METHODS: FacWide antibiotic consumption and incident HO-CDI were tallied on a
      monthly basis and standardized, from January 2013 through April 2015. Spearman
      rank-order correlation coefficients were calculated using matched-months analysis
      and a 1-month delay. Regression analyses were performed, with P < .05 considered
      statistically significant. RESULTS: FacWide analysis identified a matched-months
      correlation between ceftriaxone and HO-CDI (rho = 0.44, P = .018). A unit of stem
      cell transplant recipients did not have significant correlation between
      carbapenems and HO-CDI in matched months (rho = 0.37, P = .098), but a
      significant correlation was observed when a 1-month lag was applied (rho = 0.54,
      P = .014). DISCUSSION: Three statistically significant lag associations were
      observed between FacWide/unit-level antibiotic consumption and HO-CDI, and 1
      statistically significant nonlagged association was observed FacWide. Antibiotic
      consumption may convey extended ward-level risk for incident CDI. CONCLUSIONS:
      Consumption of antibiotic agents may have immediate and prolonged influence on
      incident CDI. Additional studies are needed to investigate the immediate and
      delayed associations between antibiotic consumption and C difficile colonization,
      infection, and transmission at the hospital level.

PMID- 29169939
TI  - The association between hypercholesterolemia and sitosterolemia, and report of a
      sitosterolemia kindred.
AB  - BACKGROUND: Sitosterolemia is associated with increases in intestinal sterol
      absorption, low-density lipoprotein cholesterol (LDL-C), and cardiovascular
      disease risk. OBJECTIVE: We examined the relationship between
      hypercholesterolemia and sitosterolemia in a large population and report a new
      sitosterolemia case. METHODS: Plasma sterol concentrations were measured by gas
      chromatography/mass spectrometry, and LDL-C by direct assay. RESULTS: Of 207,926
      subjects tested, 4.3% had LDL-C >=190 mg/dL. Plasma beta-sitosterol
      concentrations >=8.0 mg/L (99th percentile) were found in 4.3% of these subjects
      vs 0.72% with LDL-C <130 mg/dL. Among all subjects, 0.050% had beta-sitosterol
      levels >=15.0 mg/L, consistent with sitosterolemia, while among those with LDL-C
      >=190 mg/dL, 0.334% had this rare disorder. A 13-year-old boy with the highest
      LDL-C (679 mg/dL) of all subjects had planar xanthomas and a beta-sitosterol
      level of 53.5 mg/L (normal <3.3 mg/L). He was a compound heterozygote for 2 ABCG8
      mutations (p.N409D and an intron 11+2T>A splice site mutation). On a low
      cholesterol and plant-sterol diet, his LDL-C decreased to 485 mg/dL (-29%) and
      beta-sitosterol to 44.6 mg/L (-27%). On atorvastatin 20 mg/d, his LDL-C decreased
      to 299 mg/dL (-38%). With added ezetimibe 10 mg/d, his LDL-C normalized to 60
      mg/dL (-80% further decrease); and his beta-sitosterol decreased to 14.1 mg/L (
      68% further decrease). CONCLUSIONS: Our data indicate that about 4% of subjects
      with LDL-C concentrations >=190 mg/dL have plasma beta-sitosterol concentrations
      above the 99th percentile and about 0.3% have concentrations consistent with
      sitosterolemia. Therefore, this diagnosis should be considered in such patients.

PMID- 29169940
TI  - Enrichment of cellulose acetate nanofibre assemblies for therapeutic delivery of
      l-tryptophan.
AB  - The essential amino acid l-tryptophan is naturally present in the body, and is
      also available as a water soluble dietary supplement. The feasibility of
      preparing enriched cellulose acetate (CA)-based fibres as a vehicle for
      therapeutic delivery of such biomolecules was investigated. A new ternary solvent
      system consisting of acetone: N,N-dimethylacetamide: methanol (2:1:2) has been
      demonstrated to permit the solution blending of CA with the water soluble l
      tryptophan. Nanofibrous webs substantially free of structural defects were
      continuously produced with mean fibre diameters in the range of 520-1010nm,
      dependent on process parameters. Morphology and diameter of fibres were
      influenced by concentration of CA spinning solution, applied voltage and flow
      rates. The kinetic release profile of l-tryptophan from electrospun CA nanofibres
      was described by the pseudo-second order kinetic model. Fibres with mean diameter
      of 720nm provide both the highest initial desorption rate and rate constant,
      which was partially attributed to the low fibre diameter and high relative
      surface area, but also the fact that the 720nm fibres produced were the most bead
      free, providing diffusion advantages over the fibres with lowest mean diameter
      (520nm). The feasibility of combining l-tryptophan within fibres provides a
      promising route for manufacture of transdermal delivery devices.

PMID- 29169941
TI  - Synthesis, characterization and antimicrobial activity of Schiff bases modified
      chitosan-graft-poly(acrylonitrile).
AB  - Graft copolymerization of chitosan (Ch) with acrylonitrile (AN) prepared by free
      radical polymerization using potassium persulfate (PPS) as initiator.
      Optimization of Graft copolymerization of acrylonitrile on to chitosan was
      performed by studying the main parameters that affecting the grafting process
      such as initiator and monomer concentrations, reaction time and temperature of
      the polymerization process to study their influence on percent grafting (G%),
      grafting efficiency (GE%) and percent homopolymer (H%). Modification of grafted
      chitosan was done by Schiff's base derivatives using different aldehydes. They
      are characterized by FT-IR, X-ray diffraction, thermal analysis and scanning
      electron microscope. Their antibacterial activities against Streptococcus
      pneumonia (RCMB 010010), Staphylococcus aureus (RCMB 010028), as Gram-positive
      bacteria and Escherichia coli (RCMB 010052) as Gram-negative bacteria and the
      antifungal activity against Aspergillus fumigatus (RCMB 02568), Candida albicans
      (RCMB 05036) and Geotricum candidum (RCMB 05097) were examined using the
      diffusion agar technique. The obtained data proved that modified chitosan by
      grafting show better antimicrobial activities than Chitosan. Also Schiff base
      derivatives showed better antimicrobial activities than grafted chitosan.

PMID- 29169942
TI  - Injectable hydrogels for delivering biotherapeutic molecules.
AB  - To date, numerous delivery systems based on either organic or inorganic material
      have been developed to achieve efficient and sustained delivery of therapeutics.
      Hydrogels, which are three dimensional networks of crosslinked hydrophilic
      polymers, have a significant role in solving the clinical and pharmacological
      limitations of present systems because of their biocompatibility, ease of
      preparation and unique physical properties such as a tunable porous nature and
      affinity for biological fluids. Development of an in situ forming injectable
      hydrogel system has allowed excellent spatial and temporal control, unlike
      systemically administered therapeutics. Injectable hydrogel systems can offset
      difficulties with conventional hydrogel-based drug delivery systems in the clinic
      by forming a drug/gene delivery or cell-growing depot in the body with a single
      injection, thereby enabling patient compliance and comfort. Carbohydrate polymers
      are widely used for the synthesis of injectable in situ-forming hydrogels because
      of ready availability, presence of modifiable functional groups, biocompatibility
      and other physiochemical properties. In this review, we discuss different aspects
      of injectable hydrogels, such as bulk hydrogels/macrogels, microgels, and
      nanogels derived from natural polymers, and their importance in the delivery of
      therapeutics such as genes, drugs, cells or other biomolecules and how these
      revolutionary systems can complement existing therapeutic delivery systems.

PMID- 29169943
TI  - Carboxymethylated iota-carrageenan conjugated amphotericin B loaded gelatin
      nanoparticles for treating intracellular Candida glabrata infections.
AB  - Intercellular Candida glabrata infections are difficult to treat due to poor
      penetration of drugs into the fungal niche. Delivering amphotericin B (Amp B)
      into the macrophages where the pathogen inhabits is an effective solution. We are
      studying the macrophage targeting proficiency of iota-carrageenan for the
      delivery of Amp B using gelatin A nanoparticles (GNPs). The choice of gelatin A
      was the outcome of in silico inspections where the amino functionalized polymer
      having the best docking score with Amp B was selected. We prepared a sustained
      release formulation of amp B loaded carboxymethyl iota-carrageenan conjugated
      gelatin nanoparticles (CMC-Amp B-GNPs) with size 343+/-12nm and -25+/-5.3mV zeta
      potential. The formulations were found to be stable, biocompatible and non
      haemolytic. Flow cytometry analysis showed 3 fold higher uptake of CMC-GNPs
      compared to the GNPs by RAW 264.7 cells. CMC-Amp B-GNPs showed enhanced
      antifungal activity than bare Amp B and Amp B-GNPs.

PMID- 29169944
TI  - A facile comparative approach towards utilization of waste cotton lint for the
      synthesis of nano-crystalline cellulose crystals along with acid recovery.
AB  - There is a need for reuse of waste cotton lint (WCL) from the blow room of yarn
      spinning mills. The drive to use this material for the synthesis of nanocellulose
      is difficult because of the several purification/pretreatment processes. Here, we
      developed a combined single bath purification process of WCL and utilized it for
      the synthesis of nano-crystalline cellulose crystals (NCs) which are valuable
      nanomaterials with novel properties along with acid recovery for reuse. The
      micrograph of the synthesized NCs confirmed a network of nano-sized crystalline
      cellulose crystals having nano ranged diameter of NCs isolated by two processes.
      The FTIR result established the removal of impurities and hemicelluloses from
      WCL. The crystallinity index of WCL (~89.97%) is improved to ~96% and ~94% for
      sulphuric acid and nitric acid synthesized NCs (NC1 and NC2). The crystallite
      size of WCL, CTWCL, NC1, and NC2 was calculated using XRD and found to be 101.56,
      103.54, 98.81, and 95.6nm respectively. The hydrodynamic size (Z-average) (dnm),
      polydispersity index and zeta potential of NCs was also studied using dynamic
      light scattering (DLS). The thermal stability of the NC1 is better than that of
      NC2. These NCs can be used as reinforcing filler/barrier material.

PMID- 29169945
TI  - Enhanced Antibacterial effect of chitosan film using Montmorillonite/CuO
      nanocomposite.
AB  - Montmorillonite -copper oxide (MMT-CuO) nanocomposites were prepared by a facile
      and eco-friendly method and introduced into chitosan (Cs) matrix to enhance its
      optical, mechanical and antibacterial properties. The synthesized composites were
      characterized using diffuse reflectance spectroscopy (DRS), X-ray diffraction
      (XRD), field emission scanning electron microscopy (FESEM) and energy dispersive
      X-ray (EDX) spectroscopy. The antimicrobial activity of MMT-CuO nanocomposites
      showed more than 99% mortality against two Gram-negative bacterium (E.coli (PTCC
      1270), P.aeruginosa (PTCC 1430)) and two Gram-positive bacterium (S.aureus
      (PTCC1112) B.cereus (PTCC- 1015)). The effect of weight fraction of MMT-CuO
      nanocomposites (1, 3 and 5% w/w) as antibacterial nanofiller on physical,
      optical, mechanical, microstructural, and antibacterial properties of chitosan
      films were evaluated. The obtained data showed that introducing small amount MMT
      CuO to chitosan films could enhance the mechanical, antibacterial properties, and
      decreased both water solubility and UV transition with the lowest effect on the
      transparency of the films. The incorporation of 3% w/w MMT-CuO-90 nanocomposite
      into the films increased the tensile strong (TS), and elongation at break (E%)
      values 58.5% and 52.4%, respectively while reduced the water vapor permeability
      and oxygen permeability about 55% and 32%, respectively. CSG3MMT-CuO-90 films
      showed intense antibacterial activity against food borne pathogenic and more
      effective against S. aureus and B.cereus. than E.coli and P.aeruginosa.

PMID- 29169946
TI  - Preparation and characterization of chitosan - collagen peptide / oxidized konjac
      glucomannan hydrogel.
AB  - In this paper, the microbial transglutaminase (MTGase) was used as a catalyst to
      graft the collagen peptide (COP) molecules on the amino group of chitosan to
      obtain water-soluble chitosan-collagen peptide (CS-COP) derivatives. The
      preparation of composite hydrogel was via the Schiff-base reaction between the
      amino of CS-COP and the aldehyde of oxidized konjac glucomannan (OKGM). The
      hydrogels were characterized by various techniques including Fourier transform
      infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The results
      of SEM showed that the hydrogel sample had a clear and stable three-dimensional
      network structure. Meanwhile, these effects of the addition of OKGM on gelation
      time, swelling behaviors, water evaporation rate and blood coagulation capacity
      were investigated. The shortest gelation time for hydrogels was 99.3s. The
      hydrogels showed a good swelling ability and appropriate water retention
      capacity. The maximum swelling ratio of the hydrogel was 265%. Dynamic blood
      clotting test showed that the hydrogels materials had good blood coagulation
      capacity. Moreover, The biocompatibility of hydrogels was evaluated with NIH-3T3
      cells by MTT method. The results indicated that the hydrogels exhibited better
      biocompatibility. Therefore, this hydrogel has a promising potential to be
      applied as wound dressing.

PMID- 29169947
TI  - Cu(II)-carboxymethyl chitosan-silane schiff base complex grafted on nano silica:
      Structural evolution, antibacterial performance and dye degradation ability.
AB  - O-Carboxymethyl chitosan (OCMC) Schiff's base was utilized for a new class of
      organic-inorganic hybrid material by grafting it on nano-silica-silane and
      further metallated with Cu (II). Here (3-Aminopropyl) triethoxysilane (APTES) was
      used as a linker and 2-hydroxy-1-naphthaldehyde (HN) for Schiff's base formation.
      The hybrid was characterized by FTIR, TGA, powder XRD, SEM, CHN, DLS, ICP-AES,
      diffuse reflectance UV-vis and EDX spectroscopic techniques. Magnetization
      measurements were carried out by VSM at room temperature. This study explored the
      possible synergic effect of unique properties of carboxymethyl chitosan, Schiff's
      base Cu (II) complex and nano-silica towards antibacterial activity and in dye
      degradation studies. The antibacterial performance of nano-hybrid material was
      examined against both Gram-positive (Escherichia coli) and Gram-negative
      (Bacillus subtilis) bacteria. The catalytic activity of the hybrid was tested for
      degradation of reactive black 5 (RB5) through advanced oxidation processes using
      H2O2 as oxidant. The results show a high dye degradation efficiency of 93% in
      130min by the hybrid catalyst with reusability. As per published reports,
      Chitosan-Schiff's bases show strong antimicrobial activity and their Cu complexes
      exhibit good catalytic and anticancer activities. Therefore, it is expected that
      the new organic-inorganic hybrid would be highly applicable in environmental as
      well as biomedical fields.

PMID- 29169948
TI  - Biosynthesis of inulin from sucrose using inulosucrase from Lactobacillus gasseri
      DSM 20604.
AB  - Inulin is composed of fructose residues connected by beta-(2, 1) glycosidic
      linkages with many promising physiochemical and physiological properties. In this
      study, an inulin-producing inulosucrase gene from Lactobacillus gasseri DSM 20604
      was cloned, expressed and purified. SDS-PAGE and gel filtration found that the
      recombinant inulosucrase is a monomeric protein with a molecular weight of 63KDa.
      The optimal pH for its sucrose hydrolysis and transfructosylation activities was
      pH 5.5. The optimal temperatures were measured to be 45, 25, and 35 degrees C for
      sucrose hydrolysis, transfructosylation, and total activity, respectively.
      Biosynthesis studies showed that the optimal enzyme dosage was 4.5U/g sucrose.
      Higher sucrose concentrations immensely contributed to inulin biosynthesis; the
      inulin yield reached its maximum after 1.5h of reaction. Structural analyses of
      the polysaccharide produced by the recombinant enzyme from sucrose revealed that
      it is an inulin-type fructan with a molecular weight of 5.858*106Da.

PMID- 29169949
TI  - High-value utilization of eucalyptus kraft lignin: Preparation and
      characterization as efficient dye dispersant.
AB  - The dark color of industrial lignin is the main obstacle for their high value
      added use in areas such as dyestuff dispersants. A kind of light-colored
      lignosulfonate with favorable dispersibility and remarkable stain resistance is
      prepared using fractionated eucalyptus kraft lignin. The fractionated lignins
      named as D (insoluble part) and X (soluble part) and sulfonated lignin fractions
      named as SD and SX are characterized by FTIR spectroscopy, 1H NMR spectroscopy,
      GPC and brightness test. The results reveal that fraction X presents a lower
      molecular weight but a higher hydroxyl content than that of fraction D, which
      lead to the differences on the SO3H content, dispersibility and color performance
      of SD and SX. The sulfonated fractions perform a similar molecular weight to that
      of unsulfonated lignins and show light color due to the phenolic hydroxyl
      blocking of 1,4-BS (1,4-butane sultone) and the postprocessing of sodium
      borohydride. The SX that performs the best of all exhibits obvious decrease on
      phenolic hydroxyl groups and increase on brightness value which is improved by
      85.8% compared with control sample. The SX reaches the highest level (grade 5) in
      the dispersibility test and presents remarkable stain resistance on different
      textiles, especially on the dacron and cotton.

PMID- 29169950
TI  - Lactadherin: An unappreciated haemostasis regulator and potential therapeutic
      agent.
AB  - Lactadherin is a small (53-66kDa) multifunctional glycoprotein belonging to the
      secreted extracellular matrix protein family. It has a multi-domain structure and
      is involved in many biological and physiological processes, including
      phagocytosis, angiogenesis, atherosclerosis, tissue remodeling, and haemostasis
      regulation. Lactadherin binds phosphatidylserine (PS)-enriched cell surfaces in a
      receptor-independent manner. Interaction between lactadherin and PS is crucial
      for regulation of blood coagulation processes. This review summarizes recent
      knowledge on the possible role of lactadherin in haemostasis control, emphasizing
      the great significance of the interaction between lactadherin and PS expressed on
      activated platelets and extracellular vesicles. The possible role of lactadherin
      as a therapeutic target and biomarker is also discussed.

PMID- 29169951
TI  - Regulation of noradrenergic and serotonergic systems by cannabinoids: relevance
      to cannabinoid-induced effects.
AB  - The cannabinoid system is composed of Gi/o protein-coupled cannabinoid type 1
      receptor (CB1) and cannabinoid type 2 (CB2) receptor and endogenous compounds.
      The CB1 receptor is widely distributed in the central nervous system (CNS) and it
      is involved in the regulation of common physiological functions. At the neuronal
      level, the CB1 receptor is mainly placed at GABAergic and glutamatergic axon
      terminals, where it modulates excitatory and inhibitory synapses. To date, the
      involvement of CB2 receptor in the regulation of neurotransmission in the CNS has
      not been clearly shown. The majority of noradrenergic (NA) cells in mammalian
      tissues are located in the locus coeruleus (LC) while serotonergic (5-HT) cells
      are mainly distributed in the raphe nuclei including the dorsal raphe nucleus
      (DRN). In the CNS, NA and 5-HT systems play a crucial role in the control of
      pain, mood, arousal, sleep-wake cycle, learning/memory, anxiety, and rewarding
      behaviour. This review summarizes the electrophysiological, neurochemical and
      behavioural evidences for modulation of the NA/5-HT systems by cannabinoids and
      the CB1 receptor. Cannabinoids regulate the neuronal activity of NA and 5-HT
      cells and the release of NA and 5-HT by direct and indirect mechanisms. The
      interaction between cannabinoid and NA/5-HT systems may underlie several
      behavioural changes induced by cannabis such as anxiolytic and antidepressant
      effects or side effects (e.g. disruption of attention). Further research is
      needed to better understand different aspects of NA and 5-HT systems regulation
      by cannabinoids, which would be relevant for their use in therapeutics.

PMID- 29169952
TI  - Development and face validation of a Virtual Reality Epley Maneuver System
      (VREMS) for home Epley treatment of benign paroxysmal positional vertigo: A
      randomized, controlled trial.
AB  - PURPOSE: To develop and validate a smartphone based Virtual Reality Epley
      Maneuver System (VREMS) for home use. METHODS: A smartphone application was
      designed to produce stereoscopic views of a Virtual Reality (VR) environment,
      which when viewed after placing a smartphone in a virtual reality headset,
      allowed the user to be guided step-by-step through the Epley maneuver in a VR
      environment. Twenty healthy participants were recruited and randomized to undergo
      either assisted Epleys or self-administered Epleys following reading instructions
      from an Instructional Handout (IH). All participants were filmed and two expert
      Otologists reviewed the videos, assigning each participant a score (out of 10)
      for performance on each step. Participants rated their perceived workload by
      completing a validated task-load questionnaire (NASA Task Load Index) and
      averages for both groups were calculated. RESULTS: Twenty participants were
      evaluated with average age 26.4+/-7.12years old in the VREMS group and 26.1+/
      7.72 in the IH group. The VR assisted group achieved an average score of 7.78+/
      0.99 compared to 6.65+/-1.72 in the IH group. This result was statistically
      significant with p=0.0001 and side dominance did not appear to play a factor.
      Analyzing each step of the Epley maneuver demonstrated that assisted Epleys were
      done more accurately with statically significant results in steps 2-4. Results of
      the NASA-TLX scores were variable with no significant findings. CONCLUSION: We
      have developed and demonstrated face validity for VREMS through our randomized
      controlled trial. The VREMS platform is promising technology, which may improve
      the accuracy and effectiveness of home Epley treatments. LEVEL OF EVIDENCE: N/A.

PMID- 29169953
TI  - Total caloric eye speed in patients with vestibular migraine.
AB  - PURPOSE: Vestibular migraine is a common cause of dizziness that lacks a known
      objective test. This study examined total eye speed on caloric testing as a
      diagnostic marker for vestibular migraine. MATERIALS AND METHODS: Retrospective
      chart review of patients seen in a tertiary otologic practice between 2004 and
      2016 who had undergone caloric testing with water irrigation and had a diagnosis
      of vestibular migraine (n=34). A group of patients with benign paroxysmal
      positional vertigo (n=10) were used as a control group. Patients were grouped
      into quartiles based on total eye speed. RESULTS: Only patients in the lowest
      quartile (total eye speed<79) had a diagnosis of vestibular migraine. All other
      quartiles included a mix of control and vestibular migraine patients. CONCLUSION:
      Low total eye speed may be suggestive of a diagnosis of vestibular migraine, but
      most patients with vestibular migraine do not have low total eye speed.

PMID- 29169954
TI  - Application of endoscopy in otology: Changes over the last 8years in Korean
      Otological Society.
AB  - OBJECTIVES: Despite the worldwide availability of endoscope in otology, it still
      has not replaced the microscopic surgery as it has for nose surgery. In 2008, we
      administered a questionnaire on the preference of using otoscopes in Korea. In
      light of the worldwide availability of endoscopic ear surgery, we have now
      conducted a more detailed survey to determine if this preference has changed over
      8years. SUBJECTS AND METHODS: A questionnaire consisting of 10 questions was used
      to survey members of the Korean Otological Society who were actively performing
      middle ear surgery. The responses to this questionnaire were compared to those
      from 2008. The study also determined the preference for endoscope use based on
      the surgeon's experience. RESULTS: The mean surgical experience of the otologists
      was 12.7years. Endoscopy for tympanoplasty and tympanomastoidectomy increased
      over a period of 8years. In the outpatient clinic, the use of endoscopy also
      increased; over 8-year period, it surpassed the microscope as the most preferred
      diagnostic tool in the outpatient clinic. Greater than half of the operating
      rooms were equipped with endoscopic sets; however, only 4.5% of otologists
      acknowledged having endoscopic instruments. CONCLUSION: Endoscopy for surgery and
      in outpatient clinic assessment increased in otology in Korea; however,
      endoscopes have consistently been used as an adjuvant to the microscope to
      improve visualization of the tympanic cavity rather than as a tool for totally
      endoscopic ear surgery.

PMID- 29169955
TI  - A century and a half of research on the evolution of insect flight.
AB  - The gill and paranotal lobe theories of insect wing evolution were both proposed
      in the 1870s. For most of the 20th century, the paranotal lobe theory was more
      widely accepted, probably due to the fundamentally terrestrial tracheal
      respiratory system; in the 1970s, some researchers advocated for an elaborated
      gill ("pleural appendage") theory. Lacking transition fossils, neither theory
      could be definitively rejected. Winged insects are abundant in the fossil record
      from the mid-Carboniferous, but insect fossils are vanishingly rare earlier, and
      all earlier fossils are from primitively wingless insects. The enigmatic,
      isolated mandibles of Rhyniognatha (early Devonian) hint that pterygotes may have
      been present much earlier, but the question remains open. In the late 20th
      century, researchers used models to study the interaction of body and protowing
      size on solar warming and gliding abilities, and stability and glide
      effectiveness of many tiny adjustable winglets versus a single, large pair of
      immobile winglets. Living stoneflies inspired the surface-skimming theory, which
      provides a mechanism to bridge between aquatic gills and flapping wings. The
      serendipitously discovered phenomenon of directed aerial descent suggests a
      likely route to the early origin of insect flight. It provides a biomechanically
      feasible sequence from guided falls to fully-powered flight.

PMID- 29169956
TI  - Synovial fluid biomarkers: association with chronic rotator cuff tear severity
      and pain.
AB  - BACKGROUND: We tested the hypothesis that biomarkers in the synovial fluid of the
      glenohumeral (shoulder) joint are correlated with visual analog scale (VAS)
      scores, functional scores, and ultrasound findings of chronic rotator cuff tear
      (RCT) severity. METHODS: We measured biomarkers in shoulder joint synovial fluid
      of 42 patients with partial-thickness (21), nonmassive full-thickness (10), and
      massive full-thickness (11) RCTs. Pain duration, tear severity, and VAS and
      functional scores were compared with interleukin (IL) 1beta, IL-6, matrix
      metalloproteinase (MMP) 1, and MMP-13 levels. RESULTS: Both MMP-1 and MMP-13
      levels were significantly highest in the massive full-thickness group. MMP-13
      levels were significantly different between groups, but proinflammatory cytokine
      IL-1beta and IL-6 levels were not. However, IL-1beta levels were significantly
      positively correlated with VAS (r = 0.66; P <.01) and functional scores (r =
      0.61; P <.01), but IL-6, MMP-1, and MMP-13 levels were not. CONCLUSIONS: IL-1beta
      levels in shoulder synovial fluid correlated positively with shoulder pain and
      functional scores in patients with chronic RCTs. Both MMP-1 and MMP-13 levels
      were altered and increased with cuff tear severity.

PMID- 29169957
TI  - Operative versus nonoperative treatment for the management of full-thickness
      rotator cuff tears: a systematic review and meta-analysis.
AB  - BACKGROUND: Rotator cuff disease is the most common pathology of the shoulder,
      responsible for approximately 70% of clinic visits for shoulder pain. However, no
      consensus exists on the optimal treatment. The aim of this study was to analyze
      level I and II research comparing operative versus nonoperative management of
      full-thickness rotator cuff tears. METHODS: A literature search was performed, in
      accordance with the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) statement, to identify level I and II studies comparing
      operative versus nonoperative treatment of rotator cuff tears. Two independent
      researchers reviewed a total of 1013 articles. Three studies qualified for
      inclusion. These included 269 patients with 1-year follow-up. The mean age ranged
      from 59 to 65 years. Clinical outcome measures included the Constant score and
      visual analog scale (VAS) score for pain. Meta-analysis, using both fixed- and
      random-effects models, was performed on pooled results to determine overall
      significance. RESULTS: Statistically significant differences favoring surgery
      were found in both Constant and VAS scores after 1 year, with mean differences of
      5.64 (95% confidence interval, 2.06 to 9.21; P = .002) and -1.08 (95% confidence
      interval, -1.56 to -0.59; P < .0001), respectively. CONCLUSION: There was a
      statistically significant improvement in outcomes for patients managed
      operatively compared with those managed nonoperatively. The differences in both
      Constant and VAS scores were small and did not meet the minimal difference
      considered clinically significant. Larger studies with longer follow-up are
      required to determine whether clinical differences between these treatments
      become evident over time.

PMID- 29169958
TI  - Cancer evaluation in the assessment of solid organ transplant candidates: A
      systematic review of clinical practice guidelines.
AB  - BACKGROUND: Active malignancies are a contraindication to transplantation, as
      immunosuppression can lead to worse cancer outcomes; therefore, ensuring
      transplant candidates are free of malignancy before transplantation is essential.
      This systematic review assesses the availability, quality, and consistency of
      recommended cancer evaluation prior to transplantation in Clinical Practice
      Guidelines (CPGs) for the selection of solid organ transplant candidates.
      METHODS: We systematically searched for CPGs for the assessment of transplant
      candidates. The characteristics of included CPGs, strength of recommendations and
      supporting evidence were extracted. A quality assessment of the CPGs was
      conducted using the AGREE II tool. RESULTS: We identified 52 CPG for the
      selection of solid organ transplant candidates. Only 13 (25%) included
      recommendations for cancer evaluation as part of the assessment of transplant
      candidates. Most recommended age and sex appropriate cancer screening as per the
      general population guidelines. Recommendations to evaluate for other malignancies
      and for high-risk candidates were variable. Most recommendations were based on
      expert opinion and only two CPGs provided an explicit link between the
      recommendations and supporting evidence. CONCLUSION: There is a lack of clear and
      consistent recommendations for pretransplant cancer evaluation in existing CPGs.
      Although there is some consensus regarding the indication to screen for cancer as
      per the recommendations for the general population, these recommendations are not
      an appropriate risk reduction strategy for transplant candidates. Standardized
      protocols to ensure transplant candidates are cancer free prior to
      transplantation are needed.

PMID- 29169959
TI  - Chondrogenic potential of IL-10 in mechanically injured cartilage and
      cellularized collagen ACI grafts.
AB  - OBJECTIVE: The application of adjunctive mediators in Autologous chondrocyte
      implantation (ACI) techniques might be useful for improving the dedifferentiated
      chondrocyte phenotype, to support neocartilage formation and inhibit post
      traumatic cartilage destruction. In this study we examined if (a) interleukin 10
      treatment can cause chondrogenic phenotype stabilization and matrix preservation
      in mechanically injured cartilage and if (b) IL-10 can promote chondrogenesis in
      a clinically applied collagen scaffold for ACI treatment. MATERIALS AND METHODS:
      For (a) bovine articular cartilage was harvested, subjected to an axial
      unconfined injury and treated with bovine IL-10 (1-10,000 pg/ng/ml). For (b) a
      post-operatively remaining ACI graft was treated with human IL-10. Expression
      levels of type I/II/X collagen, SOX9 and aggrecan were measured by qPCR (a,b).
      After 3 weeks cell death was analyzed (nuclear blebbing and TUNEL assay) and
      matrix composition was determined by GAG measurements and immunohistochemistry
      (aggrecan, type I/II collagen, hyaluronic acid). STATISTICS: One way ANOVA
      analysis with Bonferroni's correction. RESULTS: (a) IL-10 stabilized the
      chondrogenic phenotype after injurious compression and preserved matrix
      integrity. This was indicated by elevated expression of chondrogenic markers
      COL2A1, ACAN, SOX9, while COL1A1 and COL10A1 were reduced. An increased GAG
      content paralleled this and histological staining of type 2 collagen, aggrecan
      and toluidine blue were enhanced after 3 weeks. (b) IL-10 [100 pg/ml] improved
      the chondrogenic differentiation of human chondrocytes, which was accompanied by
      cartilaginous matrix formation after 3 weeks of incubation. CONCLUSION:
      Interleukin-10 is a versatile adjuvant candidate to control the post-injurious
      environment in cartilage defects and promote chondrogenesis in ACI grafts.

PMID- 29169961
TI  - The cannabinoid transporter inhibitor OMDM-2 reduces social interaction: Further
      evidence for transporter-mediated endocannabinoid release.
AB  - Experimental evidence suggests that the transport of endocannabinoids might work
      bi-directionally. Accordingly, it is possible that pharmacological blockade of
      the latter affects not only the re-uptake, but also the release of
      endocannabinoids, thus preventing them from stimulating CB1 receptors. We used
      biochemical, pharmacological, and behavioral approaches to investigate the
      effects of the transporter inhibitor OMDM-2 on social interaction, a behavioral
      assay that requires activation of CB1 receptors. The underlying mechanisms of
      OMDM-2 were compared with those of the Fatty Acid Amide Hydrolase (FAAH)
      inhibitor URB597. Systemic administration of OMDM-2 reduced social interaction,
      but in contrast to URB597-induced social deficit, this effect was not reversed by
      the TRPV1 antagonist capsazepine. The CB1 antagonist AM251, which did not affect
      URB597-induced social withdrawal, exacerbated OMDM-2 effect. In addition, the
      potent CB1 agonist CP55,940 reversed OMDM-2-, but not URB597-, induced social
      withdrawal. Blockade of CB1 receptor by AM251 reduced social interaction and the
      cholecystokinin CCK2 antagonist LY225910 reversed this effect. Similarly, OMDM-2
      induced social withdrawal was reversed by LY225910, whereas URB597 effect was
      not. Elevation of endocannabinoid levels by URB597 or JZL184, an inhibitor of 2
      AG degradation, failed to reverse OMDM-2-induced social withdrawal, and did not
      show additive effects on cannabinoid measurements when co-administered with OMDM
      2. Taken together, these findings indicate that OMDM-2 impaired social
      interaction in a manner that is consistent with reduced activation of presynaptic
      CB1 receptors. As cannabinoid reuptake inhibitors may impair endocannabinoid
      release, caution should be taken when using these drugs to enhance
      endocannabinoid tone in vivo.

PMID- 29169960
TI  - Oxytocin inhibits the rat medullary dorsal horn Sp5c/C1 nociceptive transmission
      through OT but not V1A receptors.
AB  - The medullary dorsal horn (MDH or Sp5c/C1 region) plays a key role modulating the
      nociceptive input arriving from craniofacial structures. Some reports suggest
      that oxytocin could play a role modulating the nociceptive input at the MDH
      level, but no study has properly tested this hypothesis. Using an
      electrophysiological and pharmacological approach, the present study aimed to
      determine the effect of oxytocin on the nociceptive signaling in the MDH and the
      receptor involved. In sevoflurane, anesthetized rats, we performed
      electrophysiological unitary recordings of second order neurons at the MDH region
      responding to peripheral nociceptive-evoked responses of the first branch (V1;
      ophthalmic) of the trigeminal nerve. Under this condition, we constructed dose
      response curves analyzing the effect of local spinal oxytocin (0.2-20 nmol) on
      MDH nociceptive neuronal firing. Furthermore, we tested the role of oxytocin
      receptors (OTR) or vasopressin V1A receptors (V1AR) involved in the oxytocin
      effects. Oxytocin dose-dependently inhibits the peripheral-evoked activity in
      nociceptive MDH neurotransmission. This inhibition is associated with a blockade
      of neuronal activity of Adelta- and C-fibers. Since this antinociception was
      abolished by pretreatment (in the MDH) with the potent and selective OTR
      antagonist (L-368,899; 20 nmol) and remained unaffected after the V1AR antagonist
      (SR49059; 20 nmol or 200 nmol), the role of OTR is implied. This
      electrophysiological study demonstrates that oxytocin inhibits the peripheral
      evoked neuronal activity at MDH, through OTR activation. Thus, OTR may represent
      a new potential drug target to treat craniofacial nociceptive dysfunction in the
      MDH.

PMID- 29169962
TI  - Impaired peripheral glucose homeostasis and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common type of dementia. Recent studies
      suggest that metabolic disturbances, particularly type 2 diabetes (T2D) increase
      the risk of cognitive decline and AD. AD is also a risk factor for T2D, and a
      growing body of evidence indicates that these diseases are connected both at
      clinical and molecular levels. In T2D, peripheral insulin resistance,
      hyperglycemia and eventually insulin deficiency develops, leading to an overall
      decline in tissue health. More recently, brain insulin resistance has been shown
      to be a key feature of AD that is linked to neuronal dysfunction and cognitive
      impairment. Furthermore, both AD and T2D are amyloidogenic diseases, with
      abnormal aggregation of amyloid-beta peptide (Abeta) and islet amyloid
      polypeptide (IAPP) respectively contributing to cellular death and disease
      pathogenesis. Emerging data suggests that Abeta may have peripheral effects
      including its co-deposition in the pancreas. In this review, we discuss how
      peripheral effects of Abeta and metabolic disturbances may impact AD
      pathogenesis. This article is part of the Special Issue entitled 'Metabolic
      Impairment as Risk Factors for Neurodegenerative Disorders.'

PMID- 29169963
TI  - [Effectiveness of an assessment of computerised medical records in a university
      hospital].
AB  - OBJECTIVE: The objective of this study was to evaluate a sample of electronic
      medical records (EMR) that was sufficiently representative of the different areas
      of care in a university hospital, as well as to verify the effectiveness of an
      initial intervention through a second evaluation. METHODS: Medical records audits
      were performed in 2012 and 2013 by a blind peer review of random samples of care
      episodes, proportional to the activity of each clinical department, and with the
      same evaluation method being applied to all of them. RESULTS: More than 1,000
      episodes of care were reviewed in the 2audits. A significant improvement was
      found in hospital admissions (P=.000) in all the sections of the EMR analysed
      (P=.002), and was especially significant for the reason for consultation, for
      which its completion increased by 8.5% (p<.05), and also in the sections of the
      current process record (7.1%), physical examination (4.7%), allergies (3.9%), and
      clinical course (3.6%). The assessment of the discharge report, as a whole,
      showed an improvement (P=.001). In outpatient follow-up visits, a significant
      positive improvement was observed in the 4sections evaluated (P<.05), and also
      overall (P=.000). CONCLUSIONS: According to study conditions, the dissemination
      of the results was effective in improving the quality of the EMR. The results
      have made it possible to implement actions to review the work processes in
      certain departments, and also the partial redesign of the interface on being a
      reproducible methodology accepted by the organisation.

PMID- 29169964
TI  - [Integral incident management system in primary care: Beyond patient safety].
AB  - OBJECTIVE: To describe an integral system of notification and management of
      incidents, created by the Primary Care Team of Guineueta, as well as the main
      results after 18 months of implementation. MATERIAL AND METHOD: Using a simple
      online form, health professionals notified any type of, already categorised,
      incident. Each of them were distributed to an improvement team that assessed and
      performed the necessary actions. In addition, the Quality Committee immediately
      assessed the ones that affected patient safety, as well as the most relevant or
      repetitive ones every 6 months. RESULTS: During the first 18 months of operation
      of the system, the health professionals reported 1,267 incidents, most notably
      informatics, maintenance/technical assistance, and errors in scheduling, in
      internal circuits and protocols. Eight of them were considered to significantly
      affect patient safety. CONCLUSIONS: The implementation of the described system
      has been consolidated into our team, facilitating the detection of problems, the
      accomplishment of improvement actions and involving the professionals in the
      improvement of the quality.

PMID- 29169965
TI  - [Social capital as a determinant of public health].
AB  - BACKGROUND: The concept of Social Capital (SC), originally described by Durkheim
      (1893), is composed of dimensions related to cohesion and trust between members
      of a social group, and considered by the Word Health Organization (WHO) as part
      of the social determinants of public health for the decrease of inequities and
      inequalities in health provision. OBJECTIVE: To contribute to the dissemination
      of the concept of SC related to the social determinants of Public Health, in
      order to offer the reader in-depth content to observe the potential applications
      and practices in this field. METHODOLOGY: Literature search (Google AcademicsTM,
      PubMed, Science directTM, Ebsco HostTM). RESULTS: A total of 294 full-text
      publications were obtained, and those selected were the most influential sources
      on the evolution and application of the concept of Social Capital, socioeconomic
      development and health in the last decade. CONCLUSION: Although the current
      evidence shows that Social Capital is a determinant related to health, standards
      are still needed for its measurement. This could allow the concept to be
      measured, and facilitate its integration into the form of actions that exert
      positive influence and contribute to the implementation of institutional
      interventions planned for development and public health.

PMID- 29169966
TI  - The Finnish Prehospital Stroke Scale Detects Thrombectomy and Thrombolysis
      Candidates-A Propensity Score-Matched Study.
AB  - BACKGROUND: Prehospital stroke triage is challenged by endovascular treatment for
      large vessel occlusion (LVO) being available only in major stroke centers.
      Conjugate eye deviation (CED) is closely related to LVO, whereas common stroke
      signs (face-arm-leg-speech-visual) screen stroke. We hypothesized that combining
      CED with common stroke signs would yield a prehospital stroke scale for
      identifying both LVO and stroke in general. METHODS AND RESULTS: We
      retrospectively analyzed consecutive patients (n = 856) with prehospital Code
      Stroke (recanalization candidate). The National Institutes of Health Stroke Scale
      (NIHSS) and computed tomography were administered to patients on arrival.
      Computed tomography angiography was performed on patients with NIHSS score of 8
      or greater and considered to benefit from endovascular treatment. With random
      forest analysis and deviance analysis of the general linear model we confirmed
      the superiority of the NIHSS "Best Gaze" over other NIHSS items in detecting LVO.
      Based on this and commonly used stroke signs we presented the Finnish Prehospital
      Stroke Scale (FPSS) including dichotomized face drooping, extremity weakness,
      speech difficulty, visual disturbance, and CED. FPSS detected LVO with a
      sensitivity of 54%, specificity of 91%, positive predictive value of 48%,
      negative predictive value of 93%, and likelihood ratio of 6.2. CONCLUSIONS: Based
      on CED and universally used stroke signs, FPSS recognizes stroke in general and
      additionally, LVO as a stroke subtype comparably to other scales intended to
      detect LVO only. As the FPSS items are dichotomized, it is likely to be easy for
      emergency medical services to implement.

PMID- 29169967
TI  - Relationship between Risk Factor Control and Compliance with a Lifestyle
      Modification Program in the Stenting Aggressive Medical Management for Prevention
      of Recurrent Stroke in Intracranial Stenosis Trial.
AB  - BACKGROUND: Lifestyle modification programs have improved the achievement of risk
      factor targets in a variety of clinical settings, including patients who have
      previously suffered a stroke or transient ischemic attack and those with multiple
      risk factors. Stenting Aggressive Medical Management for Prevention of Recurrent
      Stroke in Intracranial Stenosis (SAMMPRIS) was the first vascular disease
      prevention trial to provide a commercially available lifestyle modification
      program to enhance risk factor control. We sought to determine the relationship
      between compliance with this program and risk factor control in SAMMPRIS.
      METHODS: SAMMPRIS aggressive medical management included a telephonic lifestyle
      modification program provided free of charge to all subjects (n = 451) during
      their participation in the study. Subjects with fewer than 3 expected lifestyle
      coaching calls were excluded from these analyses. Compliant subjects (n = 201)
      had  greater than or equal to 78.5% of calls (median % of completed/expected
      calls). Noncompliant subjects (n = 200) had less than 78.5% of calls or refused
      to participate. Mean risk factor values or % in-target for each risk factor was
      compared between compliant versus noncompliant subjects, using t tests and chi
      square tests. Risk factor changes from baseline to follow-up were compared
      between the groups to account for baseline differences. RESULTS: Compliant
      subjects had better risk factor control throughout follow-up for low-density
      lipoprotein, systolic blood pressure (SBP), hemoglobin A1c (HgA1c), non-high
      density lipoprotein, nonsmoking, and exercise than noncompliant subjects, but
      there was no difference for body mass index. After adjusting for baseline
      differences between the groups, compliant subjects had a greater change from
      baseline than noncompliant subjects for SBP did at 24 months and HgA1c at 6
      months. CONCLUSION: SAMMPRIS subjects who were compliant with the lifestyle
      modification program had better risk factor control during the study for almost
      all risk factors.

PMID- 29169968
TI  - Evaluation of several clinical parameters after bleaching with hydrogen peroxide
      at different concentrations: A randomized clinical trial.
AB  - OBJECTIVE: This randomized double-blind clinical trial compared tooth sensitivity
      (TS), bleaching efficacy, and cytokine levels after applying in-office bleaching
      treatments containing 15% and 35% hydrogen peroxide (HP15% and HP35%,
      respectively). METHODS: Twenty-five volunteers were randomly assigned to receive
      HP15% or HP35% treatment. The bleaching agent was applied in three 15-min
      applications per session. Two bleaching sessions were separated by a 1-week
      interval. The participants scored TS using a visual analog scale and numerical
      rating scale. Bleaching efficacy was determined by subjective and objective
      methods. Gingival crevicular fluid was collected from three jaws sites per
      patient for the analysis of fluid volume. Flow cytometry was used to analyze
      gingival crevicular fluid levels of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL
      10, tumor necrosis factor, and interferon-gamma. All measurements were obtained
      before and after bleaching. All data were statistically analyzed (alpha=0.05).
      RESULTS: The absolute risk and intensity of TS was higher for HP35% than for
      HP15% (p>0.002). One month post-bleaching, HP35% produced more bleaching than
      HP15% (p=0.02). However patient perception (p=0.06) and patient satisfaction
      (p=0.53) with regard to bleaching were not significantly different. No
      significant differences existed in the gingival fluid volume (p>0.38) or in any
      cytokine level (p>0.05) for either HP concentration. CONCLUSION: Treatment: with
      HP35% is more effective than HP15%, but generates a greater risk and intensity of
      TS. No inflammatory changes occurred despite the difference in the HP
      concentrations. CLINICAL SIGNIFICANCE: Hydrogen peroxide at a lower concentration
      (e.g., 15%) should be considered a good treatment alternative for in-office
      bleaching because the higher concentration for in-office bleaching generates a
      greater risk and intensity of TS for patients.

PMID- 29169970
TI  - Bark cells and xylem cells in Japanese white birch twigs initiate deacclimation
      at different temperatures.
AB  - Appropriate timing of cold deacclimation is an important component of winter
      survival of perennial plants, such as trees, in temperate and boreal zones.
      Recently, concerns about predicted global climate change disturbing deacclimation
      timing have been increasing. The relationship between ambient temperatures and
      the manner by which cells' freezing resistance changes is essential for
      forecasting the timing of deacclimation. In this study, Japanese white birch
      twigs that underwent deacclimation treatment at a constant temperature of -2, 0,
      4, 10, or 20  degrees C were separated into bark in which cells adapted to
      subfreezing temperatures by extracellular freezing and xylem in which cells
      adapted to subfreezing temperatures by deep supercooling, and the freezing
      resistance of cells in each tissue type was investigated by measuring percentage
      electrolyte leakage. Birch cells deacclimated in a different manner according to
      tissue type. Within 7 days under deacclimation treatment, xylem cells decreased
      their freezing resistance significantly at a high subfreezing temperature (-2 
      degrees C). In contrast, bark cells required a temperature of 10 or 20  degrees C
      for a detectable decrease in freezing resistance to occur within the same period.
      At a temperature lower than 0  degrees C, bark cells did not decrease their
      freezing resistance, even after 28 days of treatment. The difference in freezing
      behavior of cells might involve the difference in how deacclimation occurred in
      bark and xylem cells.

PMID- 29169969
TI  - Higher experience of caries and lower income trajectory influence the quality of
      restorations: A multilevel analysis in a birth cohort.
AB  - OBJECTIVES: This study aimed to evaluate the quality of posterior restorations
      (amalgam or composite) placed in adults from a birth cohort and its association
      with clinical and socioeconomic determinants experienced during their life
      course. METHODS: A representative sample (n=539) of all 5914 births occurring in
      Pelotas (Brazil) in 1982 was prospectively investigated. Quality of posterior
      restorations (satisfactory or unsatisfactory) was assessed at 31 yrs-old, using
      modified USPHS criteria. Trained and calibrated dentists performed clinical
      examination. Explanatory variables included demographic and socioeconomic, oral
      health and dental service utilization patterns during the life course. Tooth
      related variables (type of tooth, material, size of cavity) were also analyzed.
      Untreated caries and socioeconomic status were assessed by group-based
      trajectories analyses. Multilevel Regression models were used to determine
      factors associated with restoration outcomes. RESULTS: In total 2123 restorations
      (53% composite) were evaluated of which 107 (5%) were assessed as failed. The
      main reasons for failure were tooth/restoration fracture (50.5%) and secondary
      caries (30.7%). Failures in posterior restorations showed a significant
      association with socioeconomic aspects (lower tertile of income at age 30 -
      prevalence ratio (PR) 2.21 [95% CI 1.19-4.09]), clinical variables (trajectory of
      higher untreated caries - PR 2.11 [95% CI 1.23-3.61]) and also with tooth-related
      factors (Restorations involving three or more surfaces - PR 5.51 [95% CI 3.30
      9.19]) after adjustment for each other. CONCLUSIONS: These findings suggest that,
      although tooth-related variables have an important role in restoration longevity,
      patient-related factors, such as socioeconomic variables and untreated caries are
      also associated with failure and should be taken into account when evaluating
      longevity of posterior restorations. CLINICAL SIGNIFICANCE: This was the first
      study assessing long-term trajectory of untreated caries, showing an association
      between higher experience of caries during the life-course and unsatisfactory
      restorations. The findings suggest that individual related factors should be
      considered when planning treatment and in future research evaluating the
      longevity of dental restorations.

PMID- 29169971
TI  - Comparison of prostate distortion by inflatable and rigid endorectal MRI coils in
      permanent prostate brachytherapy imaging.
AB  - PURPOSE: To study the deformation of the prostate by a rigid reusable endorectal
      coil and a balloon-type endorectal coil (BTC) during MRI of the prostate in
      brachytherapy imaging. METHODS AND MATERIALS: The prostate gland was contoured on
      157 MRI scans from 52 prostate cancer patients undergoing brachytherapy. The
      curvature of the posterior prostate surface deformation was computed as a measure
      of prostate distortion and compared between scans with a BTC, rigid endorectal
      coil (REC), or no endorectal coil. For the nine patients who had MRIs with all
      three endorectal scenarios, a mean prostate deformation vector was also
      calculated between scenarios using deformable image registration. These measures
      of prostate distortion were compared with the prostate anterior-to-posterior to
      left-to-right ratio (AP/LR) on the largest prostate axial slice. RESULTS:
      Significant differences in prostate curvature were found between scans without an
      endorectal coil versus a REC versus a BTC (p < 0.001). The mean prostate
      deformation was 3.9 mm due to the BTC and 2.0 mm for the REC (p = 0.012). The
      mean AP/LR ratio was 0.62 with a BTC versus 0.76 without a coil or 0.73 with a
      REC (p < 0.001), but no difference existed between scans with a REC versus no
      coil (p = 0.7). The AP/LR ratio showed moderate correlation with prostate
      curvature (r = 0.48), and with mean prostate deformation (r = -0.64 to 0.68).
      CONCLUSIONS: The REC caused minimal deformation of the prostate compared with a
      BTC with adequate MR image quality, and calculation of the cross-sectional AP/LR
      ratio on the largest axial prostate slice can serve as a simple measure of
      prostate distortion.

PMID- 29169972
TI  - Detection of circulating IgG autoantibody to FcepsilonRIalpha in sera from
      chronic spontaneous urticaria patients.
AB  - BACKGROUNDS: Chronic spontaneous urticaria (CSU) is a common skin disorder
      characterized by itchy wheals of at least 6 weeks in duration, wherein the
      autoimmune mechanism is involved to activate IgE receptors (FcepsilonRIalpha) on
      mast cells. We aimed to assess levels of IgG autoantibody against
      FcepsilonRIalpha in sera from CSU patients using dot-blot immunoassay. METHODS:
      We performed a hospital-based cross-sectional study of 125 CSU patients (64 ASST
      positive, 61 ASST-negative) and 64 age-and sex-matched healthy controls. The cut
      off value of IgG FcepsilonRIalpha autoantibody was determined as the mean
      intensity plus two standard deviations of values in controls. Positivity for IgG
      autoantibody to FcepsilonRIalpha was analyzed according to clinical parameters of
      disease duration, urticaria activity score (UAS), ASST, response to antihistamine
      treatment, complement levels, and the presence of other autoantibodies.
      Nonparametric tests were applied for statistical analyses. RESULTS: IgG
      positivity to FcepsilonRIalpha was noted in 24.8% of CSU patients and was
      significantly more frequent in ASST-positive patients than in ASST-negative
      patients (32.8% vs 16.4%, P = 0.040). Only 3.1% of healthy controls had this
      autoantibody. Complement 3 levels were significantly lower in anti
      FcepsilonRIalpha antibody-positive patients than antibody-negative patients
      (109.8 +/- 19.9 vs 123.1 +/- 30.9, P = 0.035). No significant associations were
      found between IgG positivity to FcepsilonRIalpha and UAS, serum total IgE levels,
      atopic status, clinical responses to antihistamines, or the presence of anti
      thyroid and anti-nuclear antibodies. CONCLUSION: These findings suggest that
      circulating IgG autoantibody to FcepsilonRIalpha in a subset of patients may be
      involved in the autoimmune mechanism of CSU. Further studies are needed to
      clarify its clinical significance.

PMID- 29169973
TI  - [Maternal death by venous thromboembolic disease].
AB  - Pregnancy and postpartum are very high-risk periods for venous thromboembolism
      events (TEE), which seems to extend far beyond the classical 6-8 weeks after
      childbirth. Pulmonary embolism (PE) is one of the 3 main causes of direct
      maternal death in western countries. Between 2010 an 2012 in France, 24 deaths
      were related to PE giving a maternal mortality ratio of 1/100,000, which is not
      different from the former report (2007-2009). PE is responsible of 9% of maternal
      deaths, in equal position with postpartum hemorrhage and amniotic fluid embolism.
      Four deaths (16%) occurred after pregnancy interruption (1 abortion, 3 medical
      interruptions), 7 (30%) during ongoing pregnancy (before 22 weeks of pregnancy)
      and 13 (54%) in the postpartum period (9 to 60 days after childbirth). Among
      these deaths, 9 occurred in extra hospital setting (at home or in the street).
      Fifty percent of these deaths seem to be avoidable, as it was in the former
      report. Main avoidability criteria were: diagnostic delay; mobilization before
      effective anticoagulation of proximal deep venous thrombosis; insufficient
      preventive treatment with low molecular weight heparin [duration and/or dose
      (obesity)]; unjustified induction of labor. Analyzing those deaths allow to
      remind that in case of high suspicion of TEE, effective anticoagulation should be
      started without delay, and that angio-TDM is not contraindicated in pregnant
      women. Low molecular weight heparin regiment should be adapted to real weight.
      Monitoring of anti-Xa activity, if not routinely recommended, is probably useful
      in case of obesity or renal insufficiency. Anticipating birth by induction of
      labor, in the absence of abnormal fetal heart rhythm, should not delay effective
      anticoagulation of near-term TEE.

PMID- 29169974
TI  - A Prospective, Multicenter Phase II Study of the Efficacy and Feasibility of 15
      minute Panitumumab Infusion Plus Irinotecan for Oxaliplatin- and Irinotecan
      refractory, KRAS Wild-type Metastatic Colorectal Cancer (Short Infusion of
      Panitumumab Trial).
AB  - BACKGROUND: In some recently updated clinical guidelines, the fully humanized
      monoclonal antibody panitumumab, combined with irinotecan, has been recommended
      as an optional third-line chemotherapy for KRAS wild-type metastatic colorectal
      cancer (mCRC). The present prospective, multicenter phase II study evaluated the
      effectiveness and safety of short 15-minute panitumumab infusions. PATIENTS AND
      METHODS: From January 2011 to December 2011, patients with KRAS wild-type mCRC
      were enrolled at 8 centers. The key eligibility criteria were age >= 20 years and
      resistance or intolerance to irinotecan, fluoropyrimidine, and oxaliplatin. All
      patients received 6 mg/kg of panitumumab and 150 mg/m2 or the previous tolerated
      dose of irinotecan, biweekly, until disease progression or unacceptable toxicity.
      The initial panitumumab infusion was 60 minutes, followed by a 30-minute infusion
      and then 15-minute infusions. The primary endpoint was the confirmed response
      rate using Response Evaluation Criteria In Solid Tumors, version 1.0. The
      secondary endpoints were progression-free survival, overall survival, and
      toxicity. The trial is registered in the University Hospital Medical Information
      Network Clinical Trials Registry (UMIN no. 000004647). RESULTS: Of the 43
      patients, the median age was 62 years (range, 32-75 years), 58% were male, and
      the Eastern Cooperative Oncology Group performance status was 0 to 1. The total
      response rate was 37.2% (95% confidence interval [CI], 23.0-53.3), and the
      confirmed response rate was 18.6% (95% CI, 8.4-33.4). The median progression-free
      and overall survival were 5.8 months (95% CI, 3.3-8.4 months) and 13.6 months
      (95% CI, 10.8-16.5 months), respectively. The most frequent grade 3/4 toxicities
      were anorexia (12%), leukopenia (9%), and neutropenia (9%). Nine patients did not
      reach the 15-minute infusion, primarily because of disease progression. No
      infusion-related reactions were observed. CONCLUSION: The short 15-minute
      panitumumab infusion regimen was well tolerated, without compromising safety or
      efficacy in patients with KRAS wild-type, oxaliplatin- and irinotecan-refractory
      mCRC.

PMID- 29169975
TI  - An Unusual Case of Colorectal Adenocarcinoma Presenting as an Anterior
      Mediastinal Mass.

PMID- 29169976
TI  - [Giant coronary aneurysms in infants with Kawasaki disease].

PMID- 29169977
TI  - [Use of eponyms in Spanish in paediatric journals over the last ten years. Is it
      changing?]

PMID- 29169978
TI  - [Prevalence of neurodevelopmental, behavioural and learning disorders in
      Pediatric Primary Care].
AB  - OBJECTIVES: To determine the prevalence of psychiatric disorders in primary care
      pediatrics in Atlantic Galicia. METHODS: An observational, descriptive, cross
      sectional prevalence study was carried out in 9 outpatient clinics in A Coruna
      and Pontevedra with a population of 8293 children between September and November
      2015. A total of 1286 randomly selected patients from 0 to 14 years of age were
      included. From the medical history was registered: age, sex, psychiatric
      diagnosis established by DSM-IV-TR criteria in its five axes, professionals who
      participated in the diagnosis and treatment of the process and what type of
      treatment was received. Authorization was obtained from the Research Ethics
      Committee of Galicia number 2015/427. RESULTS: 148 of 1286 patients presented
      psychiatric pathology (11,5% IC 95% 9.73-13,29), 68% male. Between 0 and 5years,
      the prevalence was 4.5%; between 6y and 10y, 18.5% and between 11y and 14y 22%.
      Symptoms lasted a median of 25 months. The most frequent pathologies in 1286
      patients were ADHD (5.36%), language disorders (3.42%), learning disorders
      (3.26%), anxiety-depressive disorders (2.4%) and behavior disorders (1.87%). Of
      the 148 cases, 47% had comorbidity with another mental disorder. Most of them
      required attention by multiple social, health and educational professionals; 33%
      received psychopharmacological treatment. CONCLUSIONS: The prevalence of
      psychiatric disorders in pediatric primary care is frequent, chronic and complex,
      increases with age and requires many health, educational and social resources.

PMID- 29169979
TI  - [Diagnostic imaging approach of sulfite oxidase deficiency].

PMID- 29169980
TI  - Hyponatremia as a surrogate marker for optimal diuretic selection in acute heart
      failure.

PMID- 29169981
TI  - Effects of different levels of feed intake during four short periods of gestation
      and housing systems on sows and litter performance.
AB  - The current study investigated the effects of different levels of feed intake
      during 4 short periods of gestation and of housing systems on sow and litter
      performance. A total of 255 multiparous sows were allotted to 1-4 dietary
      treatments using a randomized complete block design blocking by initial body
      weight (BW), backfat (BF) and parity. Sows were housed either in individual
      stalls (n=129) or group pens (n=126) with 55 sows in each pen with electronic sow
      feeder during gestation. All sows were fed one common corn-soybean meal-based
      diet with the amount of 1.0*maintenance energy level of feed intake (106*BW0.75)
      throughout gestation except 4 periods of 7 d when dietary treatments were imposed
      on day 27, 55, 83 and 97 of gestation. During the 4 periods, sows were fed 1 of 4
      different levels of feed intake: 0.5, 1.0, 1.5 and 2.0*maintenance energy level
      (0.5M, 1.0M, 1.5M and 2.0M, respectively). Results showed that both BW gain and
      BF change during gestation for sows on 1.5M (49.7kg and 3.1mm, respectively) and
      2.0M (52.5kg and 3.7mm, respectively) levels of feed intake were significantly
      (P<0.01) greater than sows on 0.5M (26.1kg and -0.1mm, respectively) and 1.0M
      (35.6kg and 0.1, respectively) levels of feed intake. In contrast, lactation
      weight gain for sows on 1.5M (3.3kg) and 2.0M (3.4kg) levels of feed intake
      during 4 short periods of gestation were significantly (P<0.01) less than sows on
      0.5M (18.4kg) and 1.0M (11.4kg) levels of feed intake during 4 short periods of
      gestation, whereas BF loss during lactation for sows on 1.5M (-3.6mm) level of
      feed intake during 4 short periods of gestation were significantly (P=0.03)
      higher than sows on 1.0M (-2.1mm) level of feed intake during 4 short periods of
      gestation. Additionally, average daily feed intake during lactation for sows on
      0.5M (6.6kg/d) level of feed intake during gestation tended (P=0.06) to be
      greater than sows on 2.0M (5.9kg/d) level of feed intake. There were no
      differences (P>0.1) among 4 levels of feed intake in terms of numbers of total
      born and weaning piglets. However, both piglet weight at birth (1.46, 1.52, 1.53
      and 1.51kg for piglets from sows on 0.5M, 1.0M, 1.5M and 2.0M levels of feed
      intake during gestation, respectively) and at weaning (6.37, 6.55, 6.64 and
      6.38kg for piglets from sows on 0.5M, 1.0M, 1.5M and 2.0M levels of feed intake
      during gestation, respectively) were maximized at 1.5M level of feed intake. Sows
      housed in group pens had greater (P<0.01) net BW gain (24.7 vs. 19.2kg) from day
      27 of gestation to weaning compared with sows housed in individual stalls.
      However, there were no differences (P>0.1) between the 2 housing systems in terms
      of litter size and piglet weight at birth and at weaning. In conclusion,
      increasing levels of feed intake during 4 short periods of gestation increased BW
      and BF gain during gestation and led to less BW gain and more BF loss during
      lactation. Piglet weight at birth and at weaning was maximized at 1.5M level of
      feed intake. However, housing systems did not affect reproductive performance.
      Group pen housing system may be beneficial in terms of increased overall BW gain
      during gestation and lactation.

PMID- 29169982
TI  - Systematic isolated post-dilatation of the side branch as part of the provisional
      stent technique in the percutaneous treatment of coronary bifurcations. CR12
      Registry.
AB  - AIMS: To analyse systematic isolated post-dilatation of the side branch as a part
      of provisional stent technique. METHODS: 1960 angioplasties performed in two
      centres were prospectively registered, of which 382 were coronary bifurcations
      with a side branch>2mm. In centre A, isolated post-dilatation of the side branch
      was performed regardless its impairment after main vessel stenting. In centre B,
      side branch post-dilatation was performed only if it was severely affected after
      stent implantation. RESULTS: There was no difference between the two centres in
      the rate of side branch affection after stent implantation (A: 44.6 vs B: 49.3%,
      p=0.48) nor in the procedural success rate (A: 98.6% vs B: 96.7%, p=0.45). After
      one-year follow-up, a reduction of cardiovascular events was observed in centre A
      (A: 4.4% vs B: 10.4%, p=0.043) with a trend towards lower cardiac mortality (A:
      2.2% vs B: 6.5%, p=0.093) and stent thrombosis (A: 0% vs B: 2.6%, p=0.077). There
      were no differences in the rate of myocardial infarction related to the treated
      artery (A: 1.4% vs B: 3.9%, p=0.29), or target lesion revascularization (A: 1.4%
      vs. B: 3.2%, p=0.45). CONCLUSIONS: Systematic isolated post-dilatation of the
      side branch in the provisional stent technique was associated with a high
      angiographic success rate, and a low rate of cardiovascular events during follow
      up. Although the study design does not allow definitive conclusions, this
      strategy could be considered a valid option in some cases or even as part of the
      provisional stent technique.

PMID- 29169983
TI  - Novel proctorship effectively teaches interventionists coronary artery chronic
      total occlusion lesions.
AB  - BACKGROUND: Interventionists' experience and skills are essential factors for
      successful chronic total occlusion-percutaneous coronary intervention (CTO-PCI).
      However, the construction of theoretical strategy independent from
      interventionists' procedure may also improve it. We sought to assess the
      feasibility of CTO-PCI using an educational system supported by a single expert
      proctor. METHODS: A total of 160 patients underwent CTO-PCI between 2009 and 2016
      at 92 Japanese centers in the Hands-on proctorship project. The CTO-PCI strategy
      was discussed with all participants and their specialists, before and during the
      procedure. We divided patients into 2 groups based on the CTO-PCI experience of
      their interventionist: (1) the less experienced group (CTO-PCI <=50 cases, n=65)
      and (2) the more experienced group (CTO-PCI >50 cases, n=95). Baseline
      characteristics, procedural complications, and clinical outcomes were compared
      between groups. RESULTS: No significant differences in patient age, sex,
      prevalence for coronary risk factors, and lesion complexity was observed between
      groups. The retrograde approach was used equivalently between groups (55.4% vs.
      60.0%, p=0.56), and procedural success rates were similar (96.9% vs. 90.5%,
      p=0.12). The rate of proctor's bailout for recanalization were not frequent
      between groups (4.6% vs. 5.3%, p=0.85). No procedure-related mortality was noted
      in either group. In addition, no significant differences in procedural cardiac
      complications, including coronary dissection, perforation, or tamponade, were
      observed between groups (10.8% vs. 14.7%, p=0.47). CONCLUSIONS: The expert
      supported CTO-PCI maintained high success rates regardless of interventionists'
      experience. This highlights the importance of theoretical strategy for the
      management patients undergoing CTO-PCI.

PMID- 29169984
TI  - Left Main restenosis in the DES era - a call for action.
AB  - Percutaneous treatment of the unprotected left main trunk (ULM), defined as a
      vessel without patent bypass graft either to the left circumflex (LCX) or left
      anterior descending (LAD) artery, has gained a precise role thanks to recent
      scientific evidence. Although new generation drug-eluting stents have already
      proven to be safer, there is still a consistent risk of restenosis and late
      adverse events. The optimal management of a ULM restenosis is still debated. Here
      we aim at presenting a review of the available data in literature and show our
      choice for treating it.

PMID- 29169985
TI  - Ulnar pseudoaneurysm complicating infective endocarditis. The role of
      endovascular stenting.

PMID- 29169986
TI  - Thrombolysis through a Swan-Ganz catheter in two patients with high-risk
      pulmonary embolism and absolute contraindication for systemic thrombolysis.

PMID- 29169988
TI  - The Versican G1 Fragment and Serum-Derived Hyaluronan-Associated Proteins
      Interact and Form a Complex in Granulation Tissue of Pressure Ulcers.
AB  - The hyaluronan (HA)-rich extracellular matrix plays dynamic roles during tissue
      remodeling. Versican and serum-derived HA-associated protein (SHAP),
      corresponding to the heavy chains of inter-alpha-trypsin inhibitor, are major HA
      binding molecules in remodeling processes, such as wound healing. Versican G1
      domain fragment (VG1F) is generated by proteolysis and is present in either
      remodeling tissues or the mature dermis. However, the macrocomplex formation of
      VG1F has not been clarified. Therefore, we examined the VG1F-containing
      macrocomplex in pressure ulcers characterized by chronic refractory wounds. VG1F
      colocalized with SHAP-HA in specific regions of the granulation tissue but not
      with fibrillin-1. A unique VG1F-SHAP-HA complex was isolated from granulation
      tissues using gel filtration chromatography and subsequent cesium chloride
      gradient ultracentrifugation under dissociating conditions. Consistent with this
      molecular composition, recombinant versican G1, but not versican G3, interacted
      with the two heavy chains of inter-alpha-trypsin inhibitor. The addition of
      recombinant VG1 in fibroblast cultures enhanced VG1F-SHAP-HA complex deposition
      in the pericellular extracellular matrix. Comparison with other VG1F-containing
      macrocomplexes, including dermal VG1F aggregates, versican-bound microfibrils,
      and intact versican, highlighted the tissue-specific organization of HA-rich
      extracellular matrix formation containing versican and SHAP. The VG1F-SHAP-HA
      complex was specifically detected in the edematous granulation tissues of human
      pressure ulcers and in inflamed stages in a mouse model of moist would healing,
      suggesting that the complex provides an HA-rich matrix suitable for inflammatory
      reactions.

PMID- 29169989
TI  - A Disintegrin and Metalloproteinase with Thrombospondin Motifs 18 Deficiency
      Leads to Visceral Adiposity and Associated Metabolic Syndrome in Mice.
AB  - Visceral adiposity is of greater risk than obesity in s.c. adipose tissue for
      diabetes and cardiovascular disease. Its pathogenesis remains unclear, but it is
      associated with extracellular matrix (ECM) remodeling. A disintegrin and
      metalloproteinase with thrombospondin motifs (ADAMTSs) are a family of secreted
      zinc-dependent metalloproteinases that play crucial roles in development and
      various diseases because of their ECM remodeling activity. ADAMTS18 is an orphan
      ADAMTS whose function and substrate remain unclear. Herein, we showed that
      Adamts18 mRNA was abundantly expressed in visceral (gonadal) white adipose tissue
      (vWAT) during the early stage of development after birth. Adamts18 knockout (KO)
      mice showed increased body fat percentage and larger adipocyte size in vWAT
      relative to wild-type littermates. These findings may be partly attributed to ECM
      remodeling, especially increased expression of laminin 1 and adipokine
      thrombospondin 1 in vWAT. Attenuated extracellular signal-regulated kinase 1 and
      2 activity, along with increased expression of adipocyte-specific transcription
      factors peroxisome proliferator-activated receptor-gamma, CCAAT/enhancer binding
      protein beta, and marker gene Fabp4, was detected in vWAT of Adamts18 KO mice.
      Furthermore, Adamts18 KO mice showed early metabolic syndrome, including
      hyperlipidemia, blood glucose metabolic disorder, and hypertension. ADAMTS18
      deficiency promotes atherosclerosis in apolipoprotein E-deficient mice. These
      results indicate a novel function of ADAMTS18 in vWAT development and associated
      metabolic disorders.

PMID- 29169987
TI  - The R-Enantiomer of Ketorolac Delays Mammary Tumor Development in Mouse Mammary
      Tumor Virus-Polyoma Middle T Antigen (MMTV-PyMT) Mice.
AB  - Epidemiologic studies report improved breast cancer survival in women who receive
      ketorolac (Toradol) for postoperative pain relief compared with other analgesic
      agents. Ketorolac is a racemic drug. The S-enantiomer inhibits cyclooxygenases; R
      ketorolac is a selective inhibitor of the small GTPases Ras-related C3 botulinum
      toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42), which are
      signaling molecules up-regulated during breast cancer progression and metastasis.
      The goal of this study was to determine whether R-ketorolac altered breast cancer
      development in the mouse mammary tumor virus-polyoma middle T-antigen model. Mice
      were administered ketorolac orally at 1 mg/kg twice daily to approximate the
      typical human dose. Mammary glands were analyzed for tumor number and
      immunohistochemical markers of proliferation and differentiation. R-ketorolac
      treatment significantly reduced mammary epithelial proliferation, based on Ki67
      staining, and suppressed tumor development. Proliferative mammary epithelium from
      R-ketorolac-treated mice displayed greater differentiation, based on
      significantly higher total E-cadherin and decreased keratin 5 staining than
      epithelium of placebo-treated mice. No differences were detected in estrogen
      receptor, progesterone receptor, beta-catenin, or vimentin expression between
      placebo and R-ketorolac treatment groups. These findings indicate that R
      ketorolac treatment slows tumor progression in an aggressive model of breast
      cancer. R-ketorolac may thus represent a novel therapeutic approach for breast
      cancer prevention or treatment based on its pharmacologic activity as a Rac1 and
      Cdc42 inhibitor.

PMID- 29169990
TI  - Lack of Heme Oxygenase-1 Induces Inflammatory Reaction and Proliferation of
      Muscle Satellite Cells after Cardiotoxin-Induced Skeletal Muscle Injury.
AB  - Heme oxygenase-1 (HO-1, Hmox1) regulates viability, proliferation, and
      differentiation of many cell types; hence, it may affect regeneration of injured
      skeletal muscle. Here, we injected cardiotoxin into gastrocnemius muscle of
      Hmox1+/+ and Hmox1-/- animals and analyzed cellular response after muscle injury,
      focusing on muscle satellite cells (SCs), inflammatory reaction, fibrosis, and
      formation of new blood vessels. HO-1 is strongly induced after muscle injury,
      being expressed mostly in the infiltrating leukocytes (CD45+ cells), including
      macrophages (F4/80+ cells). Lack of HO-1 augments skeletal muscle injury,
      evidenced by increased creatinine kinase and lactate dehydrogenase, as well as
      expression of monocyte chemoattractant protein-1, IL-6, IL-1beta, and insulin
      like growth factor-1. This, together with disturbed proportion of M1/M2
      macrophages, accompanied by enhanced formation of arterioles, may be responsible
      for shift of Hmox1-/- myofiber size distribution toward larger one. Importantly,
      HO-1-deficient SCs are prone to activation and have higher proliferation on
      injury. This effect can be partially mimicked by stimulation of Hmox1+/+ SCs with
      monocyte chemoattractant protein-1, IL-6, IL-1beta, and is associated with
      increased MyoD expression, suggesting that Hmox1-/- SCs are shifted toward more
      differentiated myogenic population. However, multiple rounds of
      degeneration/regeneration in conditions of HO-1 deficiency may lead to exhaustion
      of SC pool, and the number of SCs is decreased in old Hmox1-/- mice. In summary,
      HO-1 modulates muscle repair mechanisms preventing its uncontrolled acceleration.

PMID- 29169991
TI  - Progression of Type 2 Helper T Cell-Type Inflammation and Airway Remodeling in a
      Rodent Model of Naturally Acquired Subclinical Primary Pneumocystis Infection.
AB  - Subclinical primary Pneumocystis infection is the most common pulmonary infection
      in early infancy, making it important to determine whether it damages the lung.
      Pneumocystis peaks at 2 to 5 months of age, when respiratory morbidity
      coincidently increases. We have documented that Pneumocystis increases mucus
      production in infant lungs, and animal models reveal lung lesions that warrant
      characterization. Herein, immunocompetent rats infected at birth with
      Pneumocystis by cohabitation, to resemble community-acquired infection, underwent
      lung assessments at 45, 60, and 75 days of age. Lungs fixed by vascular perfusion
      to prevent collapse during necropsy were used for morphometry evaluations of
      mucus production, airway epithelial thickening, perivascular and peribronchiolar
      inflammation, and structural airway remodeling. Changes in these histologic
      features indicate lung disease. Selected immune markers were assessed in parallel
      using fresh-frozen lung tissue from sibling rats of the same cages. Sequential
      activation of NF-kappaB and an increased Gata3/T-bet mRNA level ratio, consistent
      with a type 2 helper T-cell-type inflammatory response, and subacute fibrosis
      were recognized. Therefore, documenting subclinical Pneumocystis infection
      induces lung disease in the immunocompetent host. Taken together with the peak
      age of primary Pneumocystis infection, results warrant investigating the clinical
      impact of this often subclinical infection on the severity of respiratory
      diseases in early infancy. This model can also be used to assess the effects of
      airway insults, including coinfections by recognized respiratory pathogens.

PMID- 29169994
TI  - The Limitations of "How Are You Feeling?"

PMID- 29169993
TI  - Impact of vitamin D on pregnancy-related disorders and on offspring outcome.
AB  - Observational studies from all over the world continue to find high prevalence
      rates of vitamin D insufficiency and deficiency in many populations, including
      pregnant women. Beyond its classical function as a regulator of calcium and
      phosphate metabolism, vitamin D elicits numerous effects in the human body.
      Current evidence highlights a vital role of vitamin D in mammalian gestation.
      During pregnancy, adaptations in maternal vitamin D metabolism lead to a
      physiologic increase of vitamin D levels, mainly because of an increased renal
      production, although other potential sources like the placenta are being
      discussed. A sufficient supply of mother and child with calcium and vitamin D
      during pregnancy ensures a healthy bone development of the fetus, whereas lack of
      either of these nutrients can lead to the development of rickets in the child.
      Moreover, vitamin D insufficiency during pregnancy has consistently been
      associated with adverse maternal and neonatal pregnancy outcomes. In
      multitudinous studies, low maternal vitamin D status was associated with a higher
      risk for preeclampsia, gestational diabetes mellitus and other gestational
      diseases. Likewise, several negative consequences for the fetus have been
      reported, including fetal growth restriction, increased risk of preterm birth and
      a changed susceptibility for later-life diseases. However, study results are
      diverging and causality has not been proven so far. Meta-analyses on the
      relationship between maternal vitamin D status and pregnancy outcomes revealed a
      wide heterogeneity of studied populations and the applied methodology in vitamin
      D assessment. Until today, clinical guidelines for supplementation cannot be
      based on high-quality evidence and it is not clear if the required intake for
      pregnant women differs from non-pregnant women. Long-term safety data of vitamin
      D supplementation in pregnant women has not been established and overdosing of
      vitamin D might have unfavorable effects, especially in mothers and newborns with
      mutations of genes involved in vitamin D metabolism. Reliable data from large
      observational and interventional randomized control trials are urgently needed as
      a basis for any detailed and safe recommendations for supplementation in the
      general population and, most importantly, in pregnant women. This is of utmost
      importance, as ensuring a sufficient vitamin D-supply of mother and child implies
      a great potential for the prevention of birth complications and development of
      diseases.

PMID- 29169992
TI  - HAX-1 regulates SERCA2a oxidation and degradation.
AB  - Ischemia/reperfusion injury is associated with contractile dysfunction and
      increased cardiomyocyte death. Overexpression of the hematopoietic lineage
      substrate-1-associated protein X-1 (HAX-1) has been shown to protect from
      cellular injury but the function of endogenous HAX-1 remains obscure due to early
      lethality of the knockout mouse. Herein we generated a cardiac-specific and
      inducible HAX-1 deficient model, which uncovered an unexpected role of HAX-1 in
      regulation of sarco/endoplasmic reticulum Ca-ATPase (SERCA2a) in
      ischemia/reperfusion injury. Although ablation of HAX-1 in the adult heart
      elicited no morphological alterations under non-stress conditions, it diminished
      contractile recovery and increased infarct size upon ischemia/reperfusion injury.
      These detrimental effects were associated with increased loss of SERCA2a.
      Enhanced SERCA2a degradation was not due to alterations in calpain and
      calpastatin levels or calpain activity. Conversely, HAX-1 overexpression improved
      contractile recovery and maintained SERCA2a levels. The regulatory effects of HAX
      1 on SERCA2a degradation were observed at multiple levels, including intact
      hearts, isolated cardiomyocytes and sarcoplasmic reticulum microsomes.
      Mechanistically, HAX-1 ablation elicited increased production of reactive oxygen
      species at the sarco/endoplasic reticulum compartment, resulting in SERCA2a
      oxidation and a predisposition to its proteolysis. This effect may be mediated by
      NAPDH oxidase 4 (NOX4), a novel binding partner of HAX-1. Accordingly, NOX
      inhibition with apocynin abrogated the effects of HAX-1 ablation in hearts
      subjected to ischemia/reperfusion injury. Taken together, our findings reveal a
      role of HAX-1 in the regulation of oxidative stress and SERCA2a degradation,
      implicating its importance in calcium homeostasis and cell survival pathways.

PMID- 29169995
TI  - Toward a Fully Fledged Integration of Spiritual Care and Medical Care.
AB  - In this article, we aimed to set out current problems that hinder a fully fledged
      integration of spiritual and medical care, which address these obstacles. We
      discuss the following five statements: 1) spiritual care requires a clear and
      inclusive definition of spirituality; 2) empirical evidence for spiritual care
      interventions should be improved; 3) understanding patients' experiences of
      contingency is paramount to deliver effective spiritual care; 4) attention to
      spiritual needs of patients is a task for every health care practitioner; 5)
      courses on spirituality and spiritual care should be mandatory in the medical
      curriculum. Current problems might be overcome by speaking each other's language,
      which is crucial in interdisciplinary research and in good interdisciplinary
      collaboration. Using a clear and inclusive definition of spirituality and
      substantiating spiritual care using medical standards of evidence-based practice
      is a way to speak each other's language and to increase mutual understanding.
      Furthermore, including spirituality in the medical curriculum would raise
      awareness of medical practitioners for their task of attending to patients'
      spiritual needs and, subsequently, to better and more appropriate referral for
      spiritual care.

PMID- 29169996
TI  - Analysis of different anthropometric indicators in the detection of high blood
      pressure in school adolescents: a cross-sectional study with 8295 adolescents.
AB  - BACKGROUND: High blood pressure is strongly associated with obesity in different
      populations. However, it is unclear whether different anthropometric indicators
      of obesity can satisfactorily predict high blood pressure in the school setting.
      OBJECTIVES: This study evaluated the sensitivity and specificity of body mass
      index, waist circumference, and waist to height ratio in the detection of high
      blood pressure in adolescents. METHODS: The sample consisted of 8295 adolescents
      aged 10-17 years. Weight was measured using a digital scale, height with a
      stadiometer, and waist circumference using a tape measure. Blood pressure was
      measured by an automatic blood pressure measuring device. ROC curves were used
      for the analysis of sensitivity and specificity of the three anthropometric
      indices in identifying high blood pressure. Binary Logistic Regression was used
      to assess the association of body mass index, waist circumference, and waist to
      height ratio with high blood pressure. RESULTS: Low values of sensitivity were
      observed for body mass index (0.35), waist circumference (0.37), and waist to
      height ratio (0.31) and high values of specificity for body mass index (0.86),
      waist circumference (0.82), and waist to height ratio (0.83) in the detection of
      high blood pressure. An association was observed between adolescents classified
      with high body mass index (OR=3.57 [95% CI=3.10-4.10]), waist cirumference
      (OR=3.24 [95% CI=2.83-3.72]), and waist to height ratio (OR=2.94 [95% CI=2.54
      3.40]) with high blood pressure. CONCLUSIONS: Body mass index, waist
      circumference, and waist to height ratio presented low sensitivity to identify
      adolescents with high blood pressure. However, adolescents classified with high
      body mass index, waist circumference, and waist to height ratio demonstrated a
      high association of presenting high blood pressure.

PMID- 29169998
TI  - Interaction between DRD2 and lead exposure on the cortical thickness of the
      frontal lobe in youth with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: The dopamine receptor D2 receptor (DRD2) gene and lead exposure are
      both thought to contribute to the pathophysiology of attention
      deficit/hyperactivity disorder (ADHD). ADHD is characterized by delay in brain
      maturation, most prominent in the prefrontal cortex (PFC). The D2 receptor is
      also mainly located in the PFC, and animal studies show that lead exposure
      affects the dopaminergic system of the frontal lobe, indicating an overlap in
      neural correlates of ADHD, DRD2, and lead exposure. We examined the interaction
      effects of DRD2 rs1800497 and lead exposure on the cortical thickness of the
      frontal lobe in patients with ADHD. METHODS: A 1:1 age- and gender-matched sample
      of 75 participants with ADHD and 75 healthy participants was included in the
      analysis. The interaction effects of DRD2 and lead exposure on the cortical
      thickness of 12 regions of interest in the frontal lobe were examined by
      multivariable linear regression analyses. RESULTS: When we investigated the
      DRD2*lead effects in the ADHD and HC groups separately, significant DRD2*lead
      effects were found in the ADHD group, but not in the healthy control group in
      multiple ROIs of the frontal lobe. There was a significant negative correlation
      between the cortical thickness of the right superior frontal gyrus and
      inattention scores. CONCLUSIONS: The present findings demonstrated significant
      interaction effects of DRD2 and lead exposure on the cortical thickness of the
      frontal lobe in ADHD. Replication studies with larger sample sizes, using a
      prospective design, are warranted to confirm these findings.

PMID- 29169999
TI  - Current challenges in research in suicide.

PMID- 29169997
TI  - PSD95: A synaptic protein implicated in schizophrenia or autism?
AB  - The molecular components of the postsynaptic density (PSD) in excitatory synapses
      of the brain are currently being investigated as one of the major etiologies of
      neurodevelopmental disorders such as schizophrenia (SCZ) and autism. Postsynaptic
      density protein-95 (PSD-95) is a major regulator of synaptic maturation by
      interacting, stabilizing and trafficking N-methyl-d-aspartic acid receptors
      (NMDARs) and alpha-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors
      (AMPARs) to the postsynaptic membrane. Recently, there has been overwhelming
      evidence that associates PSD-95 disruption with cognitive and learning deficits
      observed in SCZ and autism. For instance, recent genomic and sequencing studies
      of psychiatric patients highlight the aberrations at the PSD of glutamatergic
      synapses that include PSD-95 dysfunction. In animal studies, PSD-95 deficiency
      shows alterations in NMDA and AMPA-receptor composition and function in specific
      brain regions that may contribute to phenotypes observed in neuropsychiatric
      pathologies. In this review, we describe the role of PSD-95 as an essential
      scaffolding protein during synaptogenesis and neurodevelopment. More
      specifically, we discuss its interactions with NMDA receptor subunits that
      potentially affect glutamate transmission, and the formation of silent synapses
      during critical time points of neurodevelopment. Furthermore, we describe how PSD
      95 may alter dendritic spine morphologies, thus regulating synaptic function that
      influences behavioral phenotypes in SCZ versus autism. Understanding the role of
      PSD-95 in the neuropathologies of SCZ and autism will give an insight of the
      cellular and molecular attributes in the disorders, thus providing treatment
      options in patients affected.

PMID- 29170000
TI  - Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's
      disease cholinopathy in rat.
AB  - In order to find out the possible earliest biomarkers of Parkinson's disease (PD)
      cholinopathy, we followed the impact of bilateral pedunculopontine tegmental
      nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states
      architectures, all sleep states related EEG microstructures, sleep spindles, the
      basal and stimulated locomotor activity. Sleep and basal locomotor activity in
      adult Wistar rats were followed during their inactive circadian phase, and
      throughout the same aging period. The bilateral PPT lesions were done by 0.1M
      ibotenic acid (IBO) during the surgical procedure for implantation of the
      electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic
      sleep recording. The cholinergic neuronal loss was identified by NADPH -
      diaphorase histochemistry. After all sleep and behavioral recording sessions, the
      locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal
      activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic
      innervation from the PPT was expressed earlier as sleep disorder then as movement
      disorder, and it was the earliest and long-lasting at hippocampal and thalamo
      cortical level, and followed by a delayed "hypokinesia". This severe impact of a
      tonically impaired PPT cholinergic innervation was evidenced as the cholinergic
      interneuronal loss of the caudate putamen and as a suppressed c-Fos expression
      after stimulation by d-AMPH. In order how they occurred, the hippocampal non
      rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle
      (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor
      cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset
      and progression.

PMID- 29170001
TI  - Heightened cortisol response to exercise challenge in women with functional
      hypothalamic amenorrhea.
AB  - BACKGROUND: Functional hypothalamic amenorrhea is characterized by anovulation
      caused by reduced gonadotropin-releasing hormone drive and is associated with
      hypercortisolemia that has been linked to heightened hypothalamic-pituitary
      adrenal reactivity to common psychological and metabolic challenges. OBJECTIVE:
      We hypothesized that women with functional hypothalamic amenorrhea would display
      greater cortisol responses to exercise challenge than ovulatory women with
      eumenorrhea. STUDY DESIGN: We completed a cross-sectional comparison of 9 women
      with functional hypothalamic amenorrhea and 11 women with eumenorrhea who were of
      reproductive age, who weighed 90-110% ideal body weight, who did not exercise
      excessively, and who had no formal psychiatric diagnosis. Subjects completed a 20
      minute submaximal exercise challenge using a cycle ergometer in a research
      exercise laboratory. Heart rate and circulatory cortisol, glucose, and lactate
      were measured at 10-minute intervals before, during, and after the exercise
      challenge. RESULTS: Baseline (t= -10 minutes) cortisol, glucose, lactate, and
      heart rate were comparable between groups. Glucose levels rose modestly during
      exercise by 2.9% in women with eumenorrhea (P=.4) but declined by 10.6% in
      functional hypothalamic amenorrhea (P<.03). The nadir in glucose levels in
      functional hypothalamic amenorrhea occurred at the end of the 20-minute exercise
      challenge (t= +20 min). Lactate levels rose comparably in both groups (P<.01).
      Heart rate increased significantly with exercise in both groups (P<.01), but the
      increase was smaller in subjects with functional hypothalamic amenorrhea (P<.01).
      Cortisol levels increased during the exercise challenge in both groups (P<.01)
      and peaked 10 minutes after the exercise ended (t= +30 min). At peak, subjects
      with functional hypothalamic amenorrhea displayed higher cortisol levels (147+/
      22 [standard error of the mean] ng/mL) than women with eumenorrhea (96+/-12
      ng/mL; P=.05). The mean percent increase over baseline was 62% in women with
      eumenorrhea and 92% in functional hypothalamic amenorrhea. CONCLUSION: The
      heightened cortisol response to exercise in women with functional hypothalamic
      amenorrhea was associated with a decline in blood glucose level that was not
      observed in women with eumenorrhea. Women with functional hypothalamic amenorrhea
      appear to be more reactive at the endocrine level to the metabolic demand of
      exercise. Submaximal challenge unmasks underlying stress sensitivity in women
      with functional hypothalamic amenorrhea and highlights the importance of the use
      of psychological interventions for stress reduction in this population.

PMID- 29170002
TI  - VegPlate: A Mediterranean-Based Food Guide for Italian Adult, Pregnant, and
      Lactating Vegetarians.

PMID- 29170003
TI  - Exploring the functional significance of sterol glycosyltransferase enzymes.
AB  - Steroidal alkaloids (SAs) are widely synthesized and distributed in plants
      manifesting as natural produce endowed with potential for medicinal, pesticidal
      and other high-value usages. Glycosylation of these SAs raises complex and
      diverse glycosides in plant cells that indeed govern numerous functional aspects.
      During the glycosylation process of these valuable metabolites, the addition of
      carbohydrate molecule(s) is catalyzed by enzymes known as sterol
      glycosyltransferases (SGTs), commonly referred to as UGTs, leading to the
      production of steryl glycosides (SGs). The ratio of SGs and nonglyco-conjugated
      SAs are different in different plant species, however, their biosynthesis in the
      cell is controlled by different environmental factors. The aim of this review is
      to evaluate the current SGT enzyme research and the functional consequences of
      glycomodification of SAs on the physiology and plant development, which together
      are associated with the plant's primary processes. Pharmaceutical, industrial,
      and other potential uses of saponins have also been discussed and their use in
      therapeutics has been unveiled by in silico analysis. The field of
      biotransformation or conversion of nonglycosylated to glycosylated phytosterols
      by the activity of SGTs, making them soluble, available and more useful for
      humankind is the new field of interest towards drug therapy.

PMID- 29170004
TI  - Identifying Patient Attitudinal Clusters Associated with Asthma Control: The
      European REALISE Survey.
AB  - BACKGROUND: Asthma is a highly heterogeneous disease that can be classified into
      different clinical phenotypes, and treatment may be tailored accordingly.
      However, factors beyond purely clinical traits, such as patient attitudes and
      behaviors, can also have a marked impact on treatment outcomes. OBJECTIVE: The
      objective of this study was to further analyze data from the REcognise Asthma and
      LInk to Symptoms and Experience (REALISE) Europe survey, to identify distinct
      patient groups sharing common attitudes toward asthma and its management.
      METHODS: Factor analysis of respondent data (N = 7,930) from the REALISE Europe
      survey consolidated the 34 attitudinal variables provided by the study population
      into a set of 8 summary factors. Cluster analyses were used to identify patient
      clusters that showed similar attitudes and behaviors toward each of the 8 summary
      factors. RESULTS: Five distinct patient clusters were identified and named
      according to the key characteristics comprising that cluster: "Confident and self
      managing," "Confident and accepting of their asthma," "Confident but dependent on
      others," "Concerned but confident in their health care professional (HCP)," and
      "Not confident in themselves or their HCP." Clusters showed clear variability in
      attributes such as degree of confidence in managing their asthma, use of reliever
      and preventer medication, and level of asthma control. CONCLUSIONS: The 5 patient
      clusters identified in this analysis displayed distinctly different personal
      attitudes that would require different approaches in the consultation room
      certainly for asthma but probably also for other chronic diseases.

PMID- 29170005
TI  - High heterogeneity, mixed infections and new genotypes in human congenital
      toxoplasmosis cases in the mega-metropolis of Central Mexico.
AB  - Mexico presents high prevalence of Toxoplasma gondii infection, including the
      congenital form, but there are few data about the genetic diversity of the
      parasite, so we attempted parasite isolation and genotyping in nine
      mother/children pairs with congenital toxoplasmosis (CT), living in the Valley of
      Mexico, who were part of a 30 cases cohort that started 12 years ago. They were
      recruited through research projects which included pre- and postnatal screening
      of congenital infections or directly CT, and cases referred to INP for management
      because they had clinical abnormalities. Genotyping was performed by PCR-RFLP of
      SAG1, SAG2, SAG3, BTUB GRA6, c22-8, c29-2, L358, PK1 and Apico markers, followed
      by sequencing. Sixty seven percent of samples were typed for the SAG3 locus, 39%
      for Apico and 33% for BTUB, while Alt. SAG2, GRA6 and c29-2 types could be
      labelled in less cases. Type I alleles predominated, followed by II and III. We
      isolated the first strain obtained from humans in Mexico and found three
      genotypes not previously found in the world. The presence of ToxoDB#10 clonal
      type was documented in one pair, as well as mixed infections in five mothers. No
      relation of genotype or parasite load with clinical signs was found. In
      conclusion, we encountered great genetic diversity and mixed T. gondii infections
      among mother/children pairs with congenital toxoplasmosis in the mega-metropolis
      of the Valley of Mexico.

PMID- 29170006
TI  - Intraneural cyst of the supraescapular nerve: Atypical cause of peripheral nerve
      entrapment syndrome. Case report and literature review.
AB  - OBJECTIVE: Intraneural cysts are benign lesions located within the epineurium of
      some peripheral nerves and their aetiopathogenesis is controversial. Most are
      located at the level of the lower limbs. In the upper limbs, the most frequently
      affected nerve is the ulnar nerve. Suprascapular nerve entrapment syndrome due to
      the formation of an intraneural cyst is rare. In this article, we show a new case
      and perform a literature review of intraneural cysts located in the suprascapular
      nerve. METHODS: We present a 49-year-old woman with pain in the lateral shoulder
      region of several months' evolution. A brachial plexus MR showed a tumour of
      approximately 2*1.5cm, with a cystic appearance, in relation to the upper trunk
      of the right brachial plexus. RESULTS: We used a supra-infraclavicular approach.
      The cystic tumour affected the suprascapular nerve. After locating a zone on the
      surface without nervous fascicles, we performed a partial resection of the
      capsule and emptying of the cyst, with a xanthochromic gelatinous content. The
      anatomopathological examination confirmed the diagnosis of intraneural cyst.
      CONCLUSION: The suprascapular nerve is a mixed nerve, coming from the upper
      trunk. It provides the motor branches to the supraspinatus and infraspinatus
      muscle. Compression of the suprascapular nerve leads to atrophy of these muscles.
      This entity is one of the differential diagnoses in a patient with pain
      irradiating to the shoulder, and its correct treatment often results in complete
      remission of symptoms.

PMID- 29170007
TI  - Capacitation in Plant and Animal Fertilization.
AB  - Sexual reproduction relies on the successful fusion of the sperm and egg cell.
      Despite the vast differences between plants and animals, there are similarities
      at a molecular level between plant and animal reproduction. While the molecular
      basis of fertilization has been extensively studied in plants, the process of
      capacitation has received little attention until recently. Recent research has
      started to uncover the molecular basis of plant capacitation. Furthermore, recent
      studies suggest that the key molecules in plants and animal fertilization are
      functionally conserved. Here, we review new insights for our understanding of
      capacitation of pollen tube and fertilization in plants and also propose that
      there are commonalities in the process of sexual reproduction between plants and
      animals.

PMID- 29170008
TI  - Genetic Control of Root System Development in Maize.
AB  - The maize root system comprises structurally and functionally different root
      types. Mutant analyses have revealed that root-type-specific genetic regulators
      intrinsically determine the maize root system architecture. Molecular cloning of
      these genes has demonstrated that key elements of auxin signal transduction, such
      as LOB domain (LBD) and Aux/IAA proteins, are instrumental for seminal, shoot
      borne, and lateral root initiation. Moreover, genetic analyses have demonstrated
      that genes related to exocytotic vesicle docking, cell wall loosening, and
      cellulose synthesis and organization control root hair elongation. The
      identification of upstream regulators, protein interaction partners, and
      downstream targets of these genes together with cell-type-specific transcriptome
      analyses have provided novel insights into the regulatory networks controlling
      root development and architecture in maize.

PMID- 29170009
TI  - Factors Associated with Inadequate Pain Control among Postoperative Patients with
      Cancer.
AB  - Postoperative pain is considered a major, complex and multidimensional problem
      that affects the clinical and functional outcomes of patients and may contribute
      to increased postoperative complications. The goal of this study was to determine
      the prevalence of inadequate pain control and to investigate the factors
      associated with inadequate pain control among postoperative cancer patients. A
      descriptive correlational, cross-sectional design was used. The study was
      conducted at four adult inpatient oncology departments at King Hussein Cancer
      Center, a nongovernmental, nonprofit, comprehensive hospital for treating cancer
      patients in Amman, Jordan. The convenience sample of 800 cancer patients selected
      comprised postoperative patients diagnosed with cancer and aged >=18 years who
      were willing to participate and able to use the numeric rating scale. About 32.9%
      of patients had pain scores higher than 4/10 at rest, and 56.4% of patients had
      pain scores higher than 4/10 on movement. Data revealed that patients aged
      between 18 and 63 years (odds ratio [OR] = 0.196, p < .0005, and OR = 0.245, p <
      .0005) and chronic user patients (OR = 28.029, p < .0005, and OR = 10.332, p <
      .0005) had increased odds of poor pain control at rest and on movement,
      respectively. Administration of preemptive medications and of fentanyl and
      bupivacaine during the postoperative period was significantly associated with
      decreased odds of poor pain control. The intravenous route was associated with
      increased odds of poor pain control at rest and on movement (OR = 2.279, p =
      .016, and OR = 5.393, p = .012) compared with other routes, including
      combinations of the intravenous and oral or epidural route. Chronic use of pain
      medications and older age were predictors of inadequate pain control
      postoperatively. Administration of preemptive medications and of combinations of
      fentanyl and bupivacaine via the epidural route was associated with better pain
      control.

PMID- 29170010
TI  - Elongator-a tRNA modifying complex that promotes efficient translational
      decoding.
AB  - Naturally occurring modifications of the nucleosides in the anticodon region of
      tRNAs influence their translational decoding properties. Uridines present at the
      wobble position in eukaryotic cytoplasmic tRNAs often contain a 5-carbamoylmethyl
      (ncm(5)) or 5-methoxycarbonylmethyl (mcm(5)) side-chain and sometimes also a 2
      thio or 2'-O-methyl group. The first step in the formation of the ncm(5) and
      mcm(5) side-chains requires the conserved six-subunit Elongator complex. Although
      Elongator has been implicated in several different cellular processes,
      accumulating evidence suggests that its primary, and possibly only, cellular
      function is to promote modification of tRNAs. In this review, we discuss the
      biosynthesis and function of modified wobble uridines in eukaryotic cytoplasmic
      tRNAs, focusing on the in vivo role of Elongator-dependent modifications in
      Saccharomyces cerevisiae. This article is part of a Special Issue entitled: SI:
      Regulation of tRNA synthesis and modification in physiological conditions and
      disease edited by Dr. Boguta Magdalena.

PMID- 29170011
TI  - DNA melting and energetics of the double helix.
AB  - Studying melting and energetics of the DNA double helix has been one of the major
      topics of molecular biophysics over the past six decades. The main objective of
      this article is to overview the current state of the field and to emphasize that
      there are still serious gaps in our understanding of the issue. We start with a
      concise description of the commonly accepted theoretical model of the DNA
      melting. We then concentrate on studies devoted to the comparison with experiment
      of theoretically predicted melting profiles of DNAs with known sequences. For
      long DNA molecules, such comparison is significant from the basic-science
      viewpoint while an accurate theoretical description of melting of short duplexes
      is necessary for various very important applications in biotechnology. Several
      sets of DNA melting parameters, proposed within the framework of the nearest
      neighbor model, are compared and analyzed. The analysis leads to a conclusion
      that in case of long DNA molecules the consensus set of nearest neighbor
      parameters describes well the experimental melting profiles. Unexpectedly, for
      short DNA duplexes the same set of parameters hardly yields any improvement as
      compared to the simplest model, which completely ignores the effect of
      heterogeneous stacking. Possible causes of this striking observation are
      discussed. We then overview the issue of separation of base-pairing and base
      stacking contributions into the double helix stability. The recent experimental
      attempts to solve the problem are extensively analyzed. It is concluded that the
      double helix is essentially stabilized by stacking interaction between adjacent
      base pairs. Base pairing between complementary pairs does not appreciably
      contribute into the duplex stability. In the final section of the article,
      kinetic aspects of the DNA melting phenomenon are discussed. The main emphasis is
      made on the hysteresis effects often observed in melting of long DNA molecules.
      It is argued that the phenomenon can be well described via an accurate
      theoretical treatment of the random-walk model of melting kinetics of an isolated
      helical segment in DNA.

PMID- 29170012
TI  - Looking ahead to research perspectives: Comment on the paper "Modeling human
      behavior in economics and social science" by Marina Dolfin, Leone Leonida,
      Nisrine Outada.

PMID- 29170013
TI  - Evaluation of photosensitizer penetration into sound and decayed dentin: A
      photoacoustic spectroscopy study.
AB  - BACKGROUND: Photodynamic therapy (PDT) may have topical indications. In those
      cases it is important for a topical photosensitizer to penetrate into the tissue
      to which it has been applied. This study aimed to compare the penetration of two
      different concentrations of erythrosine into intact and in vitro decayed dentin
      samples. METHODS: This in vitro study evaluated erythrosine (0.3 and 5%)
      penetration into sound (intact) and decayed dentin. A total of 11 dentin discs
      were prepared and divided into two equal halves, in order to keep one half sound
      while the other half was submitted to sterilization and an in vitro
      demineralization model for 5 days. Before erythrosine application, the organic
      and inorganic composition of all samples was evaluated by Fourier Transform Raman
      spectroscopy, and after erythrosine application for 30 min, the penetration depth
      was determined by Photoacoustic spectroscopy technique. RESULTS: The results
      indicated that 0.3% erythrosine showed a higher penetration depth into sound
      dentin (p = 0.002); and 5% erythrosine higher penetration into decayed dentin (p
      < 0.001). However considering clinical parameters, no statistically significant
      difference was found between any of the conditions tested. CONCLUSIONS:
      Erythrosine demonstrated ability to penetrate into dentin, irrespective of sound
      or decayed condition. Photoacoustic spectroscopy can be considered a method for
      estimating the penetration into hard tissues, and in conjunction with Raman
      spectroscopy, these are effective methods for evaluating the spectral response of
      dentin. Considering that erythrosine is capable of penetrating into decayed
      dentin, clinical trials are needed to test the effectiveness of this
      photosensitizer in Photodynamic therapy and Antimicrobial Photodynamic therapy.

PMID- 29170014
TI  - [Treatment by stem cell therapy of erectile dysfunction of diabetic origin: State
      of the art].
AB  - PURPOSE: Review of various publications on stem cell therapy to treat erectile
      dysfunction of diabetic origin. MATERIAL AND METHODS: Bibliographic search in
      PUBMED performed using the keywords cell therapy strain/erectile dysfunction
      associated with diabetes. Among the 51 articles obtained from the PUBMED
      research, we selected 16 articles for their specificity of studying erectile
      dysfunction (DE) related to diabetes. RESULTS: Different types of stem cells have
      been studied: adipose derived mesenchymal stem cells/bone marrow derived
      mesenchymal stem cells as well as progenitor endothelial cells. The experimental
      protocols are quite similar from one study to the next with nevertheless some
      specifications concerning the studied cells and the monitoring of the latter.
      Intracavernous pressure (ICP) measured after the injection of stem cells into the
      corpus cavernosum was always significantly higher than the control populations.
      The addition of certain growth factors to stem cells by gene transfection improve
      the efficacy of the cells. No ideal tracking markers of the cells have been
      identified. CONCLUSION: The positive effect of the injection of stem cells on the
      ICP belongs to the cellular trans-differentiation effect but especially to the
      paracrine effects which have not yet been completely elucidated.

PMID- 29170015
TI  - [Detrusor sphincter disorders associated with deep endometriosis: Systematic
      review of the literature].
AB  - CONTEXT: Detrusor sphincter disorders impact quality of life in case of deep
      endometriosis. Surgery, which is one of the main treatments, is responsible of
      detrusor sphincter disorders. Since then, it is essential to look for those
      disorders and find the right medical care. OBJECTIVE: To specify the detrusor
      sphincter disorders, its links with anatomical localisation of deep endometriosis
      and its prognosis after surgery. METHODS: A literature review was carried out via
      PubMed(r) with the followings keywords: "deep endometriosis", "urinary
      disorders", "voiding dysfunction" and "urinary dysfunction". Prospective and
      retrospective studies as well as previous reviews were analyzed. RESULTS:
      Concerning bladder deep endometriosis, detrusor sphincter disorders are observed
      in more than 50%. Resection of the lesions allows a clear improvement or even a
      disappearance of the disorders. Concerning the deep endometriosis of the
      posterior part of the pelvis, disorders are highlighted even if women do not
      complain of urinary trouble. Detrusor sphincter disorders are observed in 2 to
      50% and women with colorectal localisation have the highest rate. Resection of
      the lesions improves the symptoms described preoperatively but also provides de
      novo disorders of up to 47.5%. In terms of prevention, the nerve sparing surgery
      respects the pelvic nerve plexus, and reduces post-operative morbidity to less
      than 1%. CONCLUSIONS: Detrusor sphincter disorders associated with deep
      endometriosis have a prognosis if their management is adapted. Well-conducted
      interviews and standardized questionnaires is necessary to diagnosis them.
      Urodynamic test may be discussed in case of bladder endometriosis, including for
      urinary asymptomatic patients. The management of the detrusor sphincter disorders
      requires a complete resection of the nodules of deep endometriosis. In the case
      of posterior endometriosis, a dissection must be performed respecting the
      retroperitoneal vegetative nerves.

PMID- 29170016
TI  - [Sporadic kidney cancer of young subjects: Study of the clinical and pathological
      features of a bicentric cohort].
AB  - INTRODUCTION: The epidemiology of kidney cancer is evolving with a net increase
      in the incidence of renal tumors, globally, and in young people in particular.
      OBJECTIVE: To evaluate the incidence and clinical and pathological
      characteristics of sporadic renal tumors in young subjects and their risk
      factors. MATERIAL AND METHODS: A retrospective study aimed at collecting
      clinical, epidemiological and anatomopathological information from the 118
      patients aged 18 to 40 treated for a sporadic kidney tumor in two Parisian
      university hospital centers between 2003 and 2013. RESULTS: Our study showed a
      very significant increase in the incidence of renal tumors in our 11 years of
      decline (P=6.10-15). The mode of discovery also seems to have evolved with a
      majority of tumors (67 %), due to the considerable growth of imaging in recent
      decades. We also showed a different pathological distribution compared to the
      literature with a significant increase in the number of papillary tumors (16.9 %)
      and chromophobes (15.2 %), in addition to a decrease in the number of carcinomas
      (43.2 %) as well as the appearance of a new pathological entity of particular
      clinical severity: renal carcinoma related to translocation Xp11.2 (15.3 %) (P<10
      5). Among the risk factors, hypertension seems to be a definite risk factor while
      tobacco and obesity do not have a significant influence. CONCLUSION: Our study
      showed a marked increase in the incidence of renal tumors with specific clinical
      and epidemiological features in a population of young subjects. The role and
      importance of oncogenetic management as well as the study of environmental
      factors could lead to the identification of new risk factors and corollary to
      their prevention. LEVEL OF EVIDENCE: 4.

PMID- 29170017
TI  - Follicular large cleaved cell (centrocytic) lymphoma: an unrecognized variant of
      follicular lymphoma.
AB  - The World Health Organization classification of lymphoma recommends the
      subdivision of follicular lymphoma (FL) into 3 grades (FL1-3) based on the
      average number of centroblasts per high-power field in the neoplastic follicles,
      but does not recognize a form of FL characterized by a predominance of large
      cleaved cells (centrocytes) without enough centroblasts to meet the World Health
      Organization criteria for FL3. We have classified such cases as follicular large
      cleaved cell lymphoma (FLC) and, herein, describe the pathologic and clinical
      features of 72 cases of this entity. The features of FLC include a follicular
      growth pattern with pale follicles at low magnification and frequent follicular
      and/or interfollicular fibrosis. Cytologically, the cells are predominantly large
      cleaved cells with moderately coarse to fine chromatin, absent or inconspicuous
      nucleoli, and small to moderate amounts of pale cytoplasm. The mean nuclear
      diameter of the large cleaved cells was 10.1MU, approximately twice that of small
      lymphocytes and similar to centroblasts. The t(14;18) was present in 83% of the
      cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%)
      and had high Ki67 proliferation (81%). The clinical features of patients with FLC
      were similar to those with other types of FL, and survival was excellent with
      anthracycline-based chemotherapy plus rituximab. FLC is a variant of follicular
      lymphoma which should be recognized in future lymphoma classifications because
      the diagnosis of FLC may be important for the selection of therapy.

PMID- 29170018
TI  - Ocular torsion responses to sinusoidal electrical vestibular stimulation.
AB  - BACKGROUND: Eye movements evoked by electrical vestibular stimulation (EVS) offer
      potential for diagnosing vestibular dysfunction. However, ocular recording
      techniques are often too invasive or impractical for routine clinical use.
      Furthermore, the kinematic nature of the EVS signal is not fully understood in
      terms of movement sensations. NEW METHOD: We apply sinusoidal EVS stimuli varying
      from 0.05 to 20Hz, and record the eye in darkness using an infrared camera. Eye
      movement was measured offline using commercially available software to track iris
      striations. Response gain and phase were calculated separately for eye position,
      velocity and acceleration across all frequencies, to determine how the brain
      interprets the EVS signal. RESULTS: Ocular torsion responses were observed at the
      same frequency as the stimulus, for all frequencies, while lateral/vertical
      responses were minimal or absent. Response gain and phase resembled previously
      reported responses to natural rotation, but only when analysing eye velocity, not
      position or acceleration. COMPARISON WITH EXISTING METHOD(S): Our method offers a
      simple, affordable, reliable and non-invasive method for tracking the ocular
      response to EVS. It is more convenient than scleral coil recordings, or marking
      the sclera to aid video tracking. It also allows us to assess the torsional VOR
      at frequencies not possible with natural stimuli. CONCLUSIONS: Ocular torsion
      responses to EVS can be readily assessed using sinusoidal stimuli combined with
      an infrared camera. Gain and phase analysis suggests that the central nervous
      system interprets the stimulus as head roll velocity. Future work will assess the
      diagnostic potential for patients with vestibular disorders.

PMID- 29170019
TI  - Evaluation of a rapid and sensitive RT-qPCR assay for the detection of Ebola
      Virus.
AB  - BACKGROUND: The 2013-2016 Ebola virus disease (EVD) outbreak showed a lack of
      diagnostic point-of-care methods. Currently, EBOV diagnosis relies on
      quantitative reverse-transcription-PCR (RT- qPCR), highly specific and sensitive,
      but requiring skilled personnel and well-equipped laboratories. In field
      settings, these factors and others, such as samples' time of collection and
      transportation, determine a prolonged turnaround-time to final results. In
      outbreak scenarios, a rapid and transportable method could eliminate issues of
      cohorting suspected and actual EVD patients for lack of diagnostic certainty. The
      aim of this study was the field evaluation of the new fast, easy-to-use and
      reliable RT-qPCR assay and platform for EBOV detection, developed in the
      framework of the EbolaMoDRAD project by CLONIT S.r.l. and STMicroelectronics
      S.r.l. STUDY DESIGN: We evaluated its performance during the outbreak and in
      further studies in the EVD laboratory at the Princess Christian Maternity
      Hospital (PCMH) in Freetown (Sierra Leone) run by Emergency NGO and the Italian
      National Institute for Infectious Diseases (INMI). The assay was tested on
      residual aliquots of clinical specimens from EBOV-positive or -negative patients
      (n=116, EVD prevalence 37%). RESULTS AND CONCLUSION: Overall, the test was very
      easy-to-use and the instrument was robust and reliable in field-settings. The
      sensitivity of the assay was 100% and the specificity was 98.63% (95%CI: 96.34
      100.92%). The positive and negative predictive values were 97.73 (95%CI:94.77
      100.68%) and 100%, respectively. The high sensitivity and specificity of this new
      assay indicate that it is promising for laboratory diagnosis, especially in
      resource-limited settings.

PMID- 29170020
TI  - Impact of Race on the Surgical Management of Adhesive Small Bowel Obstruction.
AB  - BACKGROUND: Small bowel obstruction (SBO) represents roughly 15% of admissions by
      general surgeons. Management of SBO relies heavily on provider judgment,
      including decisions on how long to try nonsurgical management and whether to use
      a laparoscopic or open approach when surgery is needed. Given the subjective
      nature of these decisions, it is unknown if patient race influences management of
      SBO. STUDY DESIGN: The National Surgical Quality Improvement Program was used to
      identify patients who underwent adhesiolysis or small bowel resection for
      adhesive SBO between 2010 and 2015 (n = 13,896). Adjusted logistic regression
      models incorporating patient comorbidity, American Society of Anesthesiologists
      (ASA) class, and emergency status were used to analyze odds of receiving surgery
      after 5 days from hospital admission (Eastern Association for the Surgery of
      Trauma guidelines) and of undergoing an open operation. RESULTS: Patients who
      waited more than 5 days for a procedure had greater adjusted odds of
      postoperative complication (odds ratio [OR] 1.56 95% CI 1.37 to 1.79) compared
      with those waiting 5 days or less. Similarly, open procedures had higher odds of
      complication compared with laparoscopic (OR 2.31 95% CI 2.00 to 2.68). Regression
      analysis demonstrated that black patients were significantly more likely than
      white patients to wait more than 5 days for surgery (OR 1.31 95% CI [1.13-1.53])
      and undergo open surgery (OR 1.56, 95% CI 1.36 to 1.79). There was no statistical
      difference for Hispanics patients waiting more than 5 days (OR 0.98, 95% CI 0.73
      to 1.31) or receiving open surgery (OR 0.84, 95% CI 0.70 to 1.01) compared with
      white patients. CONCLUSIONS: Clinical decisions regarding SBO management differ
      based on patient race. Future studies focusing on the surgical decision-making
      process and the influence of bias are needed.

PMID- 29170021
TI  - Chronic stress and the introduction to captivity: How wild house sparrows (Passer
      domesticus) adjust to laboratory conditions.
AB  - The conditions of captivity can cause chronic stress in wild animals. Newly
      captured animals may experience weight loss, elevated glucocorticoid hormones,
      increased heart rate, increased resting adrenomedullary activation, and an
      altered heart rate response to acute stressors. As captivity conditions persist,
      chronic stress may decrease as animals adjust to the stressors of captivity. In
      this study, house sparrows (Passer domesticus) were captured from the wild,
      fitted with heart rate transmitters in a minor surgical process, and individually
      housed in an indoor bird facility. Mass, baseline corticosterone, resting heart
      rate, resting adrenomedullary activation, and the acute heart rate response to a
      sudden noise were measured over the course of the first 6 weeks of captivity.
      Birds lost weight during the first weeks of captivity, which was regained by week
      5. Baseline corticosterone peaked at day 7, decreased sharply by day 11, and
      continued to decrease throughout the 6 weeks. Although heart rate in the first 24
      h could not be collected, daytime heart rate decreased from day 1 through day 20,
      where it reached a stable plateau. Daytime heart rate variability decreased
      through the entire 6 weeks, which may indicate a gradual shift from sympathetic
      to parasympathetic nervous system regulation of heart rate. The acute heart rate
      response to a sudden noise lasted longer at day 6 than earlier or later in
      captivity. In conclusion, the data indicate that the different physiological
      systems associated with chronic stress adjust to captivity over different
      timelines.

PMID- 29170022
TI  - Functional analysis of the promoter of the molt-inhibiting hormone (mih) gene in
      mud crab Scylla paramamosain.
AB  - In this study, the 5'-flanking region of molt-inhibiting hormone (MIH) gene was
      cloned by Tail-PCR. It is 2024 bp starting from the translation initiation site,
      and 1818 bp starting from the predicted transcription start site. Forecast
      analysis results by the bioinformatics software showed that the transcription
      start site is located at 207 bp upstream of the start codon ATG, and TATA box is
      located at 240 bp upstream of the start codon ATG. Potential transcription factor
      binding sites include Sp1, NF-1, Oct-1, Sox-2, RAP1, and so on. There are two CpG
      islands, located at -25- +183 bp and -1451- -1316 bp respectively. The
      transfection results of luciferase reporter constructs showed that the core
      promoter region was located in the fragment -308 bp to -26 bp. NF-kappaB and RAP1
      were essential for mih basal transcriptional activity. There are three kinds of
      polymorphism CA in the 5'-flanking sequence, and they can influence mih promoter
      activity. These findings provide a genetic foundation of the further research of
      mih transcription regulation.

PMID- 29170023
TI  - Novel biallelic TRNT1 mutations resulting in sideroblastic anemia, combined B and
      T cell defects, hypogammaglobulinemia, recurrent infections, hypertrophic
      cardiomyopathy and developmental delay.

PMID- 29170024
TI  - Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET
      inhibitors.
AB  - Within the last decade, the Bromodomain and Extra-Terminal domain family (BET) of
      proteins have emerged as promising drug targets in diverse clinical indications
      including oncology, auto-immune disease, heart failure, and male contraception.
      The BET family consists of four isoforms (BRD2, BRD3, BRD4, and BRDT/BRDT6) which
      are distinguished by the presence of two tandem bromodomains (BD1 and BD2) that
      independently recognize acetylated-lysine (KAc) residues and appear to have
      distinct biological roles. BET BD1 and BD2 bromodomains differ at five positions
      near the substrate binding pocket: the variation in the ZA channel induces
      different water networks nearby. We designed a set of congeneric 2- and 3
      heteroaryl substituted tetrahydroquinolines (THQ) to differentially engage bound
      waters in the ZA channel with the goal of achieving bromodomain selectivity.
      SJ830599 (9) showed modest, but consistent, selectivity for BRD2-BD2. Using
      isothermal titration calorimetry, we showed that the binding of all THQ analogs
      in our study to either of the two bromodomains was enthalpy driven. Remarkably,
      the binding of 9 to BRD2-BD2 was marked by negative entropy and was entirely
      driven by enthalpy, consistent with significant restriction of conformational
      flexibility and/or engagement with bound waters. Co-crystallography studies
      confirmed that 9 did indeed stabilize a water-mediated hydrogen bond network.
      Finally, we report that 9 retained cytotoxicity against several pediatric cancer
      cell lines with EC50 values comparable to BET inhibitor (BETi) clinical
      candidates.

PMID- 29170026
TI  - Nose-to-brain peptide delivery - The potential of nanotechnology.
AB  - Nose-to-brain (N-to-B) delivery offers to protein and peptide drugs the
      possibility to reach the brain in a non-invasive way. This article is a
      comprehensive review of the state-of-the-art of this emerging peptide delivery
      route, as well as of the challenges associated to it. Emphasis is given on the
      potential of nanosized drug delivery carriers to enhance the direct N-to-B
      transport of protein or peptide drugs. In particular, polymer- and lipid- based
      nanocarriers are comparatively analyzed in terms of the influence of their
      physicochemical characteristics and composition on their in vivo fate and
      efficacy. The use of biorecognitive ligands and permeation enhancers in order to
      enhance their brain targeting efficiency is also discussed. The article concludes
      highlighting the early stage of this research field and its still unveiled
      potential. The final message is that more explicatory PK/PD studies are required
      in order to achieve the translation from preclinical to the clinical development
      phase.

PMID- 29170025
TI  - Design and synthesis of highly selective pyruvate dehydrogenase complex E1
      inhibitors as bactericides.
AB  - In order to obtain PDHc-E1 inhibitors with high selectivity and efficacy, four
      series (7, 12, 15, and 19) of 35 novel 4-aminopyrimidine derivatives were
      rationally designed and synthesized based on the binding site of ThDP in E. coli
      PDHc-E1. 12, 15, and 19 were confirmed to be potent inhibitors against E. coli
      PDHc-E1. Selected compounds 12g, 12i, 15f, and 19a showed negligible inhibition
      against porcine PDHc-E1. To understand their selectivity, the interaction of
      inhibitor and E. coli PDHc-E1 or porcine PDHc-E1 was studied by molecular
      docking. The newly introduced acylhydrazone and N-phenylbenzamide moieties could
      form stronger interaction by hydrogen bond at the active site of E. coli PDHc-E1
      compared with that of porcine PDHc-E1. A part of title compounds as potent PDHc
      E1 inhibitors also exhibited notable antibacterial activity. In particular, 12e,
      12f, 12g, 12o, and 19a exhibited 72-92% inhibition against Xanthomonas oryzae pv.
      Oryzae and Ralstonia solanacearum at 100 MUg/mL, which was better than
      thiodiazole-copper (34 and 29%, respectively) and bismerthiazol (56 and 55%,
      respectively). The results proved that we could obtain effective bactericidal
      compounds as highly selective PDHc inhibitors by rational molecular design
      utilizing the binding model of active site of E. coli PDHc-E1.

PMID- 29170027
TI  - UVA irradiation of BrU-substituted DNA in the presence of Hoechst 33258.
AB  - Given that our knowledge of DNA repair is limited because of the complexity of
      the DNA system, a technique called UVA micro-irradiation has been developed that
      can be used to visualize the recruitment of DNA repair proteins at double-strand
      break (DSB) sites. Interestingly, Hoechst 33258 was used under micro-irradiation
      to sensitize 5-bromouracil (BrU)-labelled DNA, causing efficient DSBs. However,
      the molecular basis of DSB formation under UVA micro-irradiation remains unknown.
      Herein, we investigated the mechanism of DSB formation under UVA micro
      irradiation conditions. Our results suggest that the generation of a uracil-5-yl
      radical through electron transfer from Hoechst 33258 to BrU caused DNA cleavage
      preferentially at self-complementary 5'-AABrUBrU-3' sequences to induce DSB. We
      also investigated the DNA cleavage in the context of the nucleosome to gain a
      better understanding of UVA micro-irradiation in a cell-like model. We found that
      DNA cleavage occurred in both core and linker DNA regions although its efficiency
      reduced in core DNA.

PMID- 29170028
TI  - Identification of cytotoxic, glutathione-reactive moieties inducing accumulation
      of reactive oxygen species via glutathione depletion.
AB  - Reactive oxygen species (ROS) play an essential role in the survival and
      progression of cancer. Moderate oxidative stress drives proliferation, whereas
      high levels of ROS induce cytotoxicity. Compared to cancer cells, healthy cells
      often exhibit lower levels of oxidative stress. Elevation of cellular ROS levels
      by small molecules could therefore induce cancer-specific cytotoxicity. We have
      employed high-throughput phenotypic screening to identify inducers of ROS
      accumulation. We found 4,5-dihalo-2-methylpyridazin-3-one (DHMP) and 2,3,4,5(6)
      tetrachloro-6(5)-methylpyridine (TCMP) moieties to strongly deplete GSH, to cause
      ROS accumulation and to induce cell death. Small molecules containing these
      fragments will most likely share the same properties and should therefore be
      carefully considered in the development of bioactive molecules.

PMID- 29170029
TI  - Crucial but understudied: incentives in HIV research.

PMID- 29170032
TI  - Negative Valence Life Events Promote Breast Cancer Development.
AB  - BACKGROUND: The influence of stress on breast cancer risk remains unknown. The
      goal of the present study was to determine the effect of stress in the form of
      salient positive and negative valence life events (LEs) on primary invasive
      breast cancer risk. We hypothesized that salient negative LEs would increase
      breast cancer risk and salient positive LEs would attenuate this increased risk.
      PATIENTS AND METHODS: We used a case-control design with 664 cases identified
      through the Cancer Surveillance Program of Orange County and 203 population-based
      controls. Participants completed a risk factor questionnaire, which included a LE
      section. Fourteen salient LEs of positive or negative valence were used to
      quantify stress exposure. A baseline model was constructed, and odds ratios (ORs)
      were calculated using multivariate unconditional logistic regression. RESULTS:
      Negative LEs were associated with increased breast cancer risk. The OR for >= 4
      negative LEs showed a 2.81-fold increase in breast cancer risk (OR, 2.81; 95%
      confidence interval [CI], 1.47-5.36). A significant dose-response relationship
      between lifetime negative valence LEs and breast cancer risk was found. Previous
      personal illness increased breast cancer risk by 3.6-fold (OR, 3.60; 95% CI, 2.50
      5.20). In contrast, abortion was associated with a 45% decrease in breast cancer
      risk (OR, 0.55; 95% CI, 0.34-0.89). Salient positive LEs did not have a
      significant effect on breast cancer risk. However, they seemed to buffer the
      adverse effect of salient negative LEs on breast cancer risk. CONCLUSION: The
      findings from the present study support the role of salient negative LEs in
      promoting breast cancer development, with a possible buffering effect of salient
      positive LEs.

PMID- 29170031
TI  - Development of a new protein labeling system to map subunits and domains of
      macromolecular complexes for electron microscopy.
AB  - Several gene fusion technologies have been successfully applied to label
      particular subunits or domains within macromolecular complexes to enable
      positional mapping of electron microscopy (EM) density maps, but exogenous fusion
      of a protein domain into the target polypeptide can cause unwanted structural and
      functional outcomes. Fab fragments from antibodies can be used as labeling
      reagents during EM visualization without gene manipulation of the target protein,
      but this method requires a panel of high-affinity antibodies that recognize a
      wide variety of epitopes. Linear peptide tags and their anti-tag antibodies can
      be used but they have a limited mapping ability as their placement is usually
      limited to the terminal regions of a protein. The PA dodecapeptide epitope tag
      (GVAMPGAEDDVV), forms a tight beta-turn in the antigen binding pocket of its
      antibody (NZ-1). This capability allows for insertion of the PA tag into various
      surface-exposed loops within a multi-domain cell adhesion receptor, alphaIIbbeta3
      integrin. We confirmed that the purified PA-tagged integrin ectodomain fragments
      can form a stable complex with NZ-1 Fab. Negative stain EM of the various
      integrin-NZ-1 complexes revealed that a majority of the particles exhibited a
      clear density corresponding to the NZ-1 Fab; and the positions of the bound Fab
      were in good agreement with the predicted location of the inserted PA tag. The
      high-affinity and insertion-compatibility of the PA tag system allowed us to
      develop a new EM labeling methodology applicable to proteins for which good
      antibodies are not available.

PMID- 29170030
TI  - Economic incentives for HIV testing by adolescents in Zimbabwe: a randomised
      controlled trial.
AB  - BACKGROUND: HIV testing is the important entry point for HIV care and prevention
      service, but uptake of HIV testing and thus coverage of antiretroviral therapy
      are much lower in older children and adolescents than in adults. We investigated
      the effect of economic incentives provided to caregivers of children aged 8-17
      years on uptake of HIV testing and counselling in Harare, Zimbabwe. METHODS: This
      randomised controlled trial was nested within a household HIV prevalence survey
      of children aged 8-17 years in Harare. Households with one or more survey
      participants whose HIV status was unknown were eligible to participate in the
      trial. Eligible households were randomly assigned (1:1:1) to either receive no
      incentive, receive a fixed US$2 incentive, or participate in a lottery for $5 or
      $10 if the participant presented for HIV testing and counselling at a local
      primary health-care centre. The survey fieldworkers who enrolled participants
      were not blinded to trial arm allocation, but the statistician was blinded for
      analysis of outcome. The primary outcome was the proportion of households in
      which at least one child had an HIV test within 4 weeks of enrolment. HIV test
      uptake in the incentivised groups was compared with uptake in the non
      incentivised group using logistic regression, adjusting for community and number
      of children as fixed effects and research assistant as a random effect. All
      analyses were by intention to treat. The trial is registered with the Pan African
      Clinical Trials Registry, number PACTR201605001615280. FINDINGS: Between Aug 4,
      and Dec 18, 2015, 2050 eligible households were enrolled in the prevalence
      survey. 649 (32%) households were assigned no incentive, 740 (34%) households
      were assigned a $2 incentive, and 661 (32%) households were assigned to lottery
      participation. Children were unavailable in 148 households in the no-incentive
      group, 63 households in the $2 incentive group, and 81 households in the lottery
      group. 1688 households had at least one child with unknown HIV status and were
      enrolled into the trial. 22 households had no undiagnosed child, and one
      household refused consent. The primary outcome of HIV testing was assessed in 472
      (28%) households in the no-incentive group, 654 (39%) households in the $2
      incentive group, and 562 (33%) households in the lottery group. At least one
      child was HIV tested in 93 (20%) households in the no-incentive group, in 316
      (48%) households in the $2 incentive group (adjusted odds ratio 3.67, 95% CI 2.77
      4.85; p<0.0001), and in 223 (40%) of 562 households in the lottery group (2.66,
      2.00-3.55; p<0.0001). No adverse events were reported. INTERPRETATION: Fixed
      incentives and lottery-based incentives increased the uptake of HIV testing by
      older children and adolescents, a key hard-to-reach population. This strategy
      would be sustainable in the context of vertical HIV infection as repeated testing
      would not be necessary until sexual debut. FUNDING: Wellcome Trust.

PMID- 29170033
TI  - 6-Hydroxydopamine induces autophagic flux dysfunction by impairing transcription
      factor EB activation and lysosomal function in dopaminergic neurons and SH-SY5Y
      cells.
AB  - Autophagy deregulation has been implicated in Parkinson's disease (PD), yet the
      role of autophagy in neuronal survival remains controversial. In this study, we
      comprehensively investigated the time-course of autophagy-related markers in 6
      OHDA-induced Parkinsonian rat models and assessed its effect on the state of
      autophagic flux both in vivo and in vitro. We observed an early activation of
      autophagy followed by autophagic flux impairment, which was confirmed with
      autophagy inhibitor chloroquine in vivo and Ad-GFP-mCherry-LC3-infected SH-SY5Y
      cells in vitro. In addition, 6-OHDA not only remarkably reduced the expression
      level of lysosome-associated membrane protein 1 (Lamp1), but also impaired the
      hydrolase activities of lysosomal proteases. Transcription factor EB (TFEB), a
      key transcription factor controlling lysosome biogenesis, was also significantly
      downregulated by 6-OHDA and its nuclear translocation was inhibited as well,
      which could account for the impaired lysosomal function. Promoting lysosome
      biogenesis through TFEB overexpression could protect SH-SY5Y cells against 6-OHDA
      induced neurotoxicity. The above findings demonstrated that autophagic flux
      dysfunction was closely associated with 6-OHDA-induced neurotoxicity and
      highlighted the importance of functional lysosomes and homeostatic autophagic
      flux in developing therapeutic agents for PD.

PMID- 29170034
TI  - Bioequivalence of locally acting lozenges: Evaluation of critical in vivo
      parameters and first steps towards a bio-predictive in vitro test method.
AB  - Locally-acting lozenges are among the most common types of solid dosage forms
      applied in the oral cavity. Since no guidance on the in vitro demonstration of
      local bioequivalence is available, we wanted to develop a new bio-predictive test
      method for dissolution of lozenges based on a set of physiological parameters
      relevant to lozenge dissolution in the oral cavity. An in vivo sucking study
      determining the impact of different lozenge (candy) bases and flavours on sucking
      times, saliva osmolality and salivary flow rates was performed in 6 volunteers.
      In vivo sucking times were compared with in vitro dissolution times observed in
      experiments with official dissolution methods. In vitro dissolution times of all
      formulations were significantly longer than average in vivo sucking times (20-30
      vs. <5 min) indicating that official test methods are not applicable for
      predicting in vivo dissolution of lozenges. Therefore, we developed and evaluated
      a novel test apparatus enabling the simulation of forces applied by tongue and
      hard palate during sucking. Results obtained in a first set of in vitro
      experiments came very close to those obtained in vivo. This novel in vitro
      approach is thus very promising in terms of predicting the bioequivalence of
      locally-acting lozenges.

PMID- 29170035
TI  - Titrating Oxygen Requirements During Exercise: Evaluation of a Standardized
      Single Walk Test Protocol.
AB  - BACKGROUND: Oxygen supplementation for exercise-induced hypoxemia is a common
      clinical practice that improves exercise tolerance. However, we know of no
      standardized exercise oxygen titration protocol using a single walk test. We
      report our experience with a protocol developed in our laboratory. METHODS: Our
      protocol is based on the 6-min walk test (6MWT). Pulse oximetry readings (oxygen
      saturation [Spo2]) are monitored, and supplemental oxygen is added in 2 L/min
      increments to keep Spo2 > 88%. This continues for at least 6 min of walking with
      the Spo2 remaining > 88% for at least 3 min. The records of consecutive patients
      over 4 months undergoing this procedure were reviewed for test performance,
      oxygen titration results, and adverse events. RESULTS: Two hundred twenty-two
      patients were tested; only two prematurely terminated the protocol because of
      intractable dyspnea. One hundred fifty-six patients (38%) required oxygen
      supplementation, with the first titration most commonly occurring between 1 and 2
      min of walking. Nine of the patients had the first titration after 5 min of
      walking. The average test duration was 7 min (maximum, 15 min). The average
      number of titrations was 2.2 (maximum six). Sixteen patients could not maintain
      Spo2 > 88% for 3 min despite administration of 15 L/min of supplemental oxygen
      (maximal dose). CONCLUSIONS: Our protocol was easily performed as a modification
      of a standard 6MWT with no serious adverse events. Because it is based on a
      widely accepted measurement of functional capabilities, and because it determined
      a stable final oxygen dose for >= 3 min of walking in most patients, we believe
      this protocol can be easily adapted for clinical use.

PMID- 29170036
TI  - Mucins, Mucus, and Goblet Cells.
AB  - The respiratory epithelium is lined by mucus, a gel consisting of water, ions,
      proteins, and macromolecules. The major macromolecular components of mucus are
      the mucin glycoproteins, which are critical for local defense of the airway.
      There are three classes of mucins in the airways: those that are secreted but do
      not polymerize (MUC7), those that are secreted and polymerize to form gels
      (MUC5AC, MUC5B), and those that have transmembrane domains and are cell surface
      associated (MUC1, MUC4, MUC16, MUC20). The mucins are regulated at the
      transcriptional, posttranscriptional, and epigenetic levels, and
      posttranslational modifications play an important role in mucin binding and
      clearance of microbes and pollutants. The development of mice deficient in
      specific mucins, and the cystic fibrosis pig, has greatly advanced our
      understanding of the role of mucins as innate immune mediators and how mucins and
      mucus contribute to lung disease. These observations suggest new strategies to
      ameliorate mucus obstruction by targeting mucociliary clearance and mucin
      hyperconcentration. Furthermore, a polymorphism in the promoter of MUC5B is
      strongly associated with risk of developing pulmonary fibrosis, supporting a
      novel function for MUC5B to influence interstitial lung disease. Exciting new
      data support the concept not only that mucins and mucus are important for lung
      homeostasis and protection from environmental threats but also that goblet cells
      play an important role as regulators of innate immune function. These insights
      into the innate immune properties of mucins and goblet cells support a shift from
      the current paradigm of repressing increased mucin expression to targeting
      regulation of specific mucins and the abnormal airway milieu.

PMID- 29170037
TI  - Stiff and tough: a comparative study on the tensile properties of shark skin.
AB  - In sharks, the skin is a biological composite with mineralized denticles embedded
      within a collagenous matrix. Swimming performance is enhanced by the dermal
      denticles on the skin, which have drag reducing properties produced by regional
      morphological variations and changes in density along the body. We used
      mechanical testing to quantify the effect of embedded mineralized denticles on
      the quasi-static tensile properties of shark skin to failure in four coastal
      species. We investigated regional differences in denticle density and skin
      properties by dissecting skin from the underlying fascia and muscle at 10
      anatomical landmarks. Hourglass-shaped skin samples were extracted in the cranial
      to caudal orientation. Denticle density was quantified and varied significantly
      among both regions and species. We observed the greatest denticle densities in
      the cranial region of the body for the bonnethead, scalloped hammerhead, and bull
      sharks. Skin samples were then tested in tension until failure, stress strain
      curves were generated, and mechanical properties calculated. We found significant
      species and region effects for all three tensile mechanical properties. We report
      the greatest ultimate tensile strength, stiffness, and toughness near the cranial
      and lateral regions of the body for all 4 of the coastal species. We also report
      that denticle density increases with skin stiffness but decreases with toughness.

PMID- 29170038
TI  - Micromorphology of ovaries and oogenesis in Grania postclitellochaeta
      (Clitellata: Enchytraeidae).
AB  - The genus Grania comprises over 70 species of exclusively marine clitellate
      annelids belonging to the family Enchytraeidae. Morphologically, this genus is
      well separated from other enchytraeids, with thick cuticles, anterior segments I
      IV fused into a "head", chaetal bundles consisting only of one stout chaeta, and
      reduction of circular musculature. The aim of the present study is to describe
      the ovary organization and the course of oogenesis in Grania postclitellochaeta,
      and to compare it with other known systems of ovary organization and oogenesis in
      clitellate annelids, especially in enchytraeids. Generally, oogenesis in G.
      postclitellochaeta can be divided into two phases: (i) early stages of oogenesis,
      occurring within the paired ovaries - each ovary is similar to a bunch of grapes,
      where each 'lobe' is a germ-line cyst enveloped by flat somatic cells, and (ii)
      oogenesis proper, which takes place within the body lumen where each growing
      oocyte is accompanied by its own group of nurse cells. Germ cells are
      interconnected by cytoplasmic channels (intercellular bridges, ring canals) and
      form syncytial cysts. As in other clitellate annelids, the cyst center contains a
      common cytoplasm (cytophore) to which each cell is connected by one ring canal
      only. Initially, within the ovary, all interconnected cells develop synchronously
      and are morphologically similar. At the time when the cysts detach from the
      ovary, one of the interconnected cells begins to gather nutrients, grows and
      becomes an oocyte, whereas the rest of the cells (nurse cells) do not continue
      meiosis and instead seem to provide the oocyte with macromolecules and cell
      organelles. Analysis of serial sections reveals that cysts are always composed of
      16 cells - one oocyte and fifteen nurse cells. A comparative analysis showed that
      almost all features of oogenesis in G. postclitellochaeta are similar to that in
      other representatives of Enchytraeidae (mainly Enchytraeus albidus), suggesting
      evolutionary conservation of the process across this family.

PMID- 29170039
TI  - [Delineation of the surgical bed of operated brain metastases treated with
      adjuvant stereotactic irradiation: A review].
AB  - Stereotactic radiotherapy of the surgical bed of brain metastases is a technique
      that comes supplant indications of adjuvant whole brain radiotherapy after
      surgery. After a growing number of retrospective studies, a phase III trial has
      been presented and validated this indication. However, several criteria such as
      the dose, the fractionation, the use of a margin and definition of volumes remain
      to be defined. Our study consisted in making a literature review in order to
      provide a guideline of delineation of surgical beds of brain metastases, as well
      as the different modalities of their implementation process.

PMID- 29170040
TI  - Elevated production of IL-36alpha in chronic hepatitis B virus-infected patients
      correlates with viral load.
AB  - Chronic hepatitis B (CHB) infection is a typical inflammatory disease
      characterized by a dysregulated expression of cytokines, which contributes to the
      pathogenesis of chronic Hepatitis B virus (HBV) infection. IL-36 cytokines (IL
      36alpha, IL-36beta, IL-36gamma and IL-36Ra) are important players in infection
      and immunity. However, their roles in the pathogenesis of chronic HBV infection
      remain unknown. Here the circulating concentrations of IL-36 cytokines from 50
      CHB patients and 30 healthy controls were determined by enzyme-linked
      immunosorbent assay (ELISA). Sera concentrations of IL-36alpha were found to be
      significantly elevated in CHB patients, while the concentrations of IL-36beta, IL
      36gamma and IL-36Ra were not significantly different in comparison to healthy
      donors. Furthermore, increased IL-36alpha concentrations correlated positively
      with HBV-DNA levels in CHB patients. Our study suggests that IL-36alpha
      production was up-regulated during CHB infection, which could be directly related
      to HBV-DNA loads in CHB patients. The immunoregulatory role of IL-36alpha in the
      pathogenesis of chronic HBV infection should be further studied.

PMID- 29170041
TI  - NFkappaB transcription factor (p65) immunohistochemistry in leprosy dermal
      microvasculature.
AB  - Leprosy caused by Mycobacterium leprae is characterized by a spectrum of clinical
      manifestations that are determined by the predominant immunological profile of
      the host. The recruitment of leukocytes to the sites of injury can influence the
      development of these profiles. Cell adhesion molecules such as ICAM-1, VCAM-1 and
      CD62E participate in this process and their expression is regulated by
      transcriptions factors such as NFkappaB. To correlate the expression of cell
      adhesion molecules and NFkappaB (p65) in leprosy lesions, 30 skin biopsies of
      patients with leprosy [16 with the tuberculoid (TT) or borderline tuberculoid
      (BT) forms and 14 with the lepromatous (LL) or borderline lepromatous (BL) forms]
      were analyzed by immunohistochemistry. A larger mean number of cells expressing
      VCAM-1 (BT/TT: 18.28 +/- 1.4; BL/LL: 10.67 +/- 1.2; p = 0.0002), ICAM-1 (BT/TT:
      9.92 +/- 1.1; BL/LL: 5.87 +/- 1.0; p = 0.0084) and CD62E (BT/TT: 13.0 +/- 1.5;
      BL/LL: 2.58 +/- 0.3; p = 0.0001) were observed in BT and TT lesions. The mean
      number of cells expressing NFkappaB was similar in the two clinical forms (BT/TT:
      2.21 +/- 2.7; BL/LL: 2.35 +/- 3.1;p = 0.9285). No significant correlation was
      observed between expression of the transcription factor and adhesion molecules
      analyzed. The synthesis of ICAM-1, VCAM-1 and CD62E depends on the activation of
      NFkappaB, which acts synergistically with other transcription factors. Adequate
      activation of intracellular signaling pathways results in the production of
      endothelial adhesion molecules, contributing to the recruitment of cells to the
      site of injury and thus eliciting an effective inflammatory response in the
      elimination of the bacillus.

PMID- 29170042
TI  - Anti-cancer effects of Staphylococcal Enterotoxin type B on U266 cells co
      cultured with Mesenchymal Stem Cells.
AB  - BACKGROUND: Malignant plasma cells are responsible for Multiple Myeloma (MM).
      Myeloma Cells (MCs) are located in Bone Marrow (BM) and are in contact with
      stromal cells. The BM-derived Mesenchymal Stem Cells (BM-MSCs) affect MCs biology
      through different mechanisms. Currently, Staphylococcal Enterotoxin B (SEB) has
      been introduced as an anti-tumor agent that is able to kill cancer cells. The
      present study examined the effects of SEB on MCs and MSCs as an anti-tumor
      substance. METHODS: U266 cells co-cultured on BM-MSCs and treated with SEB and
      cell viability was analyzed by MTT assay and flow cytometry. The expression
      levels of IKKb, IL-6, IL-10, and TGF-beta genes were evaluated by Real Time-PCR
      technique in U266 cells and BM-MSCs. RESULTS: Data showed that in the presence of
      SEB, BM-MSCs support U266 cells proliferation and survival. Moreover, SEB, BM
      MSCs and BM-MSCs Conditioned Medium (CM) up-regulated IL-6 and IL-10 expression
      in U266 cells. Additionally, U266 cells showed increased levels in IKKb
      expression in presence of SEB or BM-MSCs, while expression of IKKb in U266 cells
      was down-regulated in coexistence of SEB with BM-MSCs or SEB with CM. Also, TGF
      beta remained without any changes. DISCUSSION: All in all, SEB can be an
      appropriate candidate to decrease proliferation and survival rate of cancer cells
      and it can make noticeable alteration in expression of some genes in U266 cells
      and BM-MSCs. Further molecular studies are needed to identify the mechanism of
      action of SEB on U266 cells and BM-MSCs.

PMID- 29170043
TI  - Green synthesis of silver nano particles from Atalantia monophylla (L) Correa
      leaf extract, their antimicrobial activity and sensing capability of H2O2.
AB  - In the present study deals with the green synthesis of silver nano particles from
      methanolic leaf extracts of Atalantia monophylla. The synthesized nano-particles
      are characterized by UV-vis spectroscopy, PL, FTIR, XRD, SEM with EDAX and TEM.
      The nano-particles are indicated in absorption peak at 404 nm in the absorption
      spectrum. Further micro graphical analysis confirmed the average size was
      estimated about 35 nm and SEAD pattern authorized well crystalline materials. The
      FTIR studies help to confirm the functional group of synthesized silver nano
      particles. The XRD data shown the crystalline nature of nano particles and EDAX
      measurement indicates the purity of silver metal. The antimicrobial effect of
      silver nanoparticles was tested on pathogenic organisms using agar well diffusion
      method. Minimum inhibitory concentration (MIC) and Minimum
      bactericidal/fungicidal concentration (MBC/MFC) were also investigated in
      different concentrations of leaf extract. The results indicated that synthesized
      silver nano particle of A. monophylla leaf extract has the potential of
      antimicrobial activity against pathogenic microorganism. In addition, this is the
      first report on leaf synthesized silver nano particles of A. monophylla. The
      antimicrobial activity against pathogenic microorganisms and the ability to
      detect hydrogen peroxide using the silver nanoparticles were confirmed which
      would find applications in the development of new antimicrobial drugs and new
      biosensors to detect the presence of hydrogen peroxide in various samples
      respectively.

PMID- 29170044
TI  - Differential gene expression in Mycobacterium bovis challenged monocyte-derived
      macrophages of cattle.
AB  - A functional genomics approach was used to examine the immune response for
      transcriptional profiling of PBMC M. bovis infected cattle and healthy control
      cattle to stimulation with bovine tuberculin (purified protein derivative PPD-b).
      Total cellular RNA was extracted from non-challenged control and M. bovis
      challenged MDM for all animals at intervals of 6 h post-challenge, in response to
      in-vitro challenge with M. bovis (multiplicity of infection 2:1) and prepared for
      global gene expression analysis using the Agilent Bovine (V2) Gene Expression
      Microarray, 8 * 60 K. The pattern of expression of these genes in PPD bovine
      stimulated PBMC provides the first description of an M. bovis specific signature
      of infection that may provide insights into the molecular basis of the host
      response to infection. Analysis of these mapped reads showed 2450 genes (1291 up
      regulated and 1158 down regulated) 462 putative natural antisense transcripts
      (354 up-regulated and 108 down regulated) that were differentially expressed
      based on sense and antisense strand data, respectively (adjusted P-value <=
      0.05). The results provided enrichment for genes involved top ten up regulated
      and down regulated panel of genes, including transcription factors proliferation
      of T and B lymphocytes. The highest differentially-expressed genes were
      associated to immune and inflammatory responses, immunity, differentiation, cell
      growth, apoptosis, cellular trafficking and regulation of lipolysis and
      thermogenesis. Microarray results were confirmed in infected cattle by RT qPCR to
      identify potential biomarkers TLR2, CD80, NFKB1, IL8, CXCL6 and ADORA3 of bovine
      tuberculosis.

PMID- 29170045
TI  - Astragalus polysaccharides inhibit avian infectious bronchitis virus infection by
      regulating viral replication.
AB  - The avian coronavirus causes infectious bronchitis (IB), which is one of the most
      serious diseases affecting the avian industry worldwide. However, there are no
      effective strategies for controlling the IB virus (IBV) at present. Therefore,
      development of novel antiviral treatment strategies is urgently required. As
      reported, astragalus polysaccharides (APS) have potential antiviral effects
      against several viruses; however, the antiviral effect of APS against IBV remains
      unclear. In this study, we explored whether APS had the potential to inhibit IBV
      infectionby utilizing several in vitro experimental approaches. To this end, the
      effect of APS on the replication of IBV was examined in chicken embryo kidney
      (CEK) cells. Viral titers were calculated by using the plaque formation assay,
      and the cytotoxicity of APS was tested by utilizing a Cell Counting Kit-8 assay.
      The expression of viral mRNA and cytokine (IL-1beta, IL-6, IL-8 and TNF-alpha)
      mRNA transcripts was determined by real-time quantitative RT-PCR(qRT-PCR). IBV
      titers in infected CEK cells treated with APS were significantly reduced in a
      dose-dependent manner, indicating that APS inhibited IBV replication in vitro. We
      also found that the decreased viral replication after APS treatment was
      associated with reduced mRNA levels of the cytokines IL-1B, IL-6, IL-8 and TNF
      alpha. In conclusion, these results suggest that APS exhibit antiviral activities
      against IBV and it may represent a potential therapeutic agent for inhibiting the
      replication of IBV.

PMID- 29170046
TI  - The Single von Willebrand factor C-domain protein (SVC) coding gene is not
      involved in the hymenoptaecin upregulation after Israeli acute paralysis virus
      (IAPV) injection in the bumblebee Bombus terrestris.
AB  - Within insects, inductions of antimicrobial peptides (AMPs) have been reported
      after different virus challenges. It is believed that this link is not directly
      induced by the virus itself, but rather indirectly induced by secondary effects
      of virus infection. Here we explored if direct sensing of the virus could trigger
      AMP expression. Recently, a cytokine-like molecule vago, a member of the Single
      von Willebrand factor C-domain (SVC) protein family, has been shown to be induced
      by virus infection in a Dicer-2 dependent manner. SVCs are also reported to be
      responsive in relation to multiple environmental challenges including bacterial
      infections and the nutritional status in the model species Drosophila
      melanogaster. Within the bumblebee Bombus terrestris only one SVC member has been
      identified and is proven to be involved in both the host antiviral defense and
      the basal expression of AMP genes, thereby it is a possible candidate linking
      virus infection and AMPs induction. Here we showed that the injection of Israeli
      acute paralysis virus (IAPV) resulted in a higher hymenoptaecin expression at
      1dpi. This expression is IAPV specific as neither injection of slow bee paralysis
      virus (SBPV) nor random dsRNA results in a similar induction at 1dpi. We could
      not prove that hymenoptaecin expression after IAPV treatment was related to
      BtSVC, as a silencing experiment did not lower hymenoptaecin induction. This
      leaves indirect activation by secondary effects of IAPV infection as a mechanism
      of AMP genes induction, or that IAPV infection influences the AMP expression
      dynamics which is initially induced by non-virus related triggers.

PMID- 29170047
TI  - Caffeic acid-assisted cross-linking catalyzed by polyphenol oxidase decreases the
      allergenicity of ovalbumin in a Balb/c mouse model.
AB  - Ovalbumin (OVA) is the most abundant egg white protein, but is also a major egg
      allergen. Desensitization of OVA may be a good way to control an egg allergy. In
      this study, caffeic acid-assisted cross-linked OVA catalyzed by polyphenol
      oxidase (PPO) was prepared, the effect of cross-linking on the allergenicity of
      OVA was tested in a Balb/c mouse model. Mice were orally sensitized with OVA or
      cross-linked OVA using cholera toxin as adjuvant. Clinical signs of allergy,
      specific antibody levels, serum histamine levels, mast cell protease-1 (mMCP-1)
      concentrations, morphological structure of duodenum, and cytokines were
      determined after mice were challenged with OVA or cross-linked OVA. Both OVA and
      cross-linked OVA induced allergic diarrhea in Balb/c mice, however, histological
      symptoms of small intestine were much milder in mice fed with cross-linked OVA
      than in those fed with OVA. A tendency toward decreased allergen-specific IgE,
      IgG, IgG1 and IgG2a levels, as well as serum histamine and mMCP-1 concentration
      were observed in cross-linked OVA group, accompanied by an inhibition of IL-4, IL
      5, IL-13 and IFN-gamma production in the stimulated spleen cell. It could be
      concluded that caffeic acid-assisted PPO-catalyzed cross-linking significantly
      reduced the potential allergenicity of OVA, but may not completely eliminate it.

PMID- 29170048
TI  - Neuroprotective effect of berberine against environmental heavy metals-induced
      neurotoxicity and Alzheimer's-like disease in rats.
AB  - Heavy metals are reported as neurodegenerative disorders progenitor. They play a
      role in the precipitation of abnormal beta-amyloid protein and hyper
      phosphorylated tau, the main hallmarks of Alzheimer's disease (AD). The present
      study aimed to validate the heavy metals-induced Alzheimer's-like disease in rats
      as an experimental model of AD and explore the therapeutic effect of berberine
      via tracking its effect on the oxidative stress-inflammatory pathway. Alzheimer's
      like disease was induced in rats orally by a mixture of aluminium, cadmium and
      fluoride for three months, followed by berberine treatment for another one month.
      Berberine significantly improved the cognitive behaviors in Morris water maze
      test and offered a protective effect against heavy metals-induced memory
      impairment. Docking results showed that berberine inhibited AChE, COX-2 and TACE.
      Matching with in silico study, berberine downregulated the AChE expression and
      inhibited its activity in the brain tissues. Also, it normalized the production
      of TNF- alpha, IL-12, IL-6 and IL-1beta. Moreover, it evoked the production of
      antioxidant Abeta40 and inhibited the formation of Abeta42, responsible for the
      aggregations of amyloid-beta plaques. Histopathological examination confirmed the
      neuroprotective effect of berberine. The present data advocate the possible
      beneficial effect of berberine as therapeutic modality for Alzheimer's disease
      via its antiinflammatory/antioxidant mechanism.

PMID- 29170049
TI  - Brachytherapy for conservative treatment of invasive penile carcinoma in older
      patients: Single institution experience.
AB  - BACKGROUND: No study has examined the possibility to perform an organ sparing
      strategy in older patients with penile carcinoma, and amputation is frequently
      proposed. We report our experience of interstitial brachytherapy for the
      conservative treatment of penile carcinoma confined to the glans in patients aged
      of 70years and more. METHODS: A total of 55 patients candidates to conservative
      brachytherapy were identified. Median age was 73.8years (range: 70-95years).
      Patients underwent a circumcision then 3-4weeks later, an interstitial
      brachytherapy was delivered, median dose of 65Gy (range 55-74Gy). Salvage surgery
      was discussed in patients with histological confirmation of residual/relapsed
      tumor. RESULTS: With median follow-up of 9.0years, eight patients (14.5%)
      experienced a relapse, including five patients with local relapse. Three patients
      with local relapse only underwent salvage penile surgery, including two partial
      glansectomies and one total penectomy, and were in second complete remission at
      last follow-up. Among 55 patients analyzed for late side effects, seven patients
      (13.0%) presented pain or ulceration, 12 (22.2%) experienced urethral or meatal
      stenosis requiring at least one dilatation, two patients (3.7%) experienced both
      ulcerations and urethral complication. Three patients (5.5%) needed partial
      glansectomy for focal necrosis. At five years, estimated overall survival rate
      was 74.5% (95%CI: 62.0-87.0%) and local relapse free rate was 91.0% (95%CI: 82.6
      99.4%). CONCLUSION: Brachytherapy is feasible in selected older patients with
      penile carcinoma, with efficacy and toxicity rates comparable to that of other
      series in younger patients.

PMID- 29170050
TI  - Identification of a pyruvate-to-lactate signature in pancreatic intraductal
      papillary mucinous neoplasms.
AB  - OBJECTIVE: We used transcriptomic profiling and immunohistochemistry (IHC) to
      search for a functional imaging strategy to resolve common problems with
      morphological imaging of cystic neoplasms and benign cystic lesions of the
      pancreas. METHODS: Resected pancreatic cancer (n = 21) and normal pancreas were
      laser-capture micro-dissected, and transcripts were quantified by RNAseq.
      Functional imaging targets were validated at the protein level by IHC on a
      pancreatic adenocarcinoma tissue microarray and a newly created tissue microarray
      of resected intraductal papillary mucinous neoplasms (IPMNs) and IPMN-associated
      adenocarcinomas. RESULTS: Genes encoding proteins responsible for cellular import
      of pyruvate, export of lactate, and conversion of pyruvate to lactate were highly
      upregulated in pancreatic adenocarcinoma compared to normal pancreas. Strong
      expression of MCT4 and LDHA was observed by IHC in >90% of adenocarcinoma
      specimens. In IPMNs, the pyruvate-to-lactate signature was significantly elevated
      in high grade dysplasia (HGD) and IPMN-associated adenocarcinoma. Additionally,
      cores containing HGD and/or adenocarcinoma exhibited a higher number of peri
      lesional stromal cells and a significant increase in peri-lesional stromal cell
      staining of LDHA and MCT4. Interestingly, the pyruvate-to-lactate signature was
      significantly upregulated in cores containing only low grade dysplasia (LGD) from
      patients with histologically confirmed IPMN-associated adenocarcinoma versus LGD
      cores from patients with non-invasive IPMNs. CONCLUSION: Our results suggest
      prospective studies with hyperpolarized [1-13C]-pyruvate magnetic resonance
      spectroscopic imaging are warranted. If these IHC results translate to functional
      imaging findings, a positive pyruvate-to-lactate imaging signature might be a
      risk factor for invasion that would warrant resection of IPMNs in the absence of
      other worrisome features.

PMID- 29170051
TI  - Multicenter study of early pancreatic cancer in Japan.
AB  - BACKGROUND/OBJECTIVES: The diagnosis of early-stage pancreatic ductal
      adenocarcinoma (PDAC) is still challenging. We conducted a multicenter study to
      clarify the clinical features of early-stage PDAC in Japan. METHODS: We collected
      patients with stage 0 and stage I PDAC according to the sixth edition of the
      Japanese Classification of Pancreatic Carcinoma. We retrospectively analyzed the
      clinical profiles including opportunities for medical examination, imaging
      modalities and findings, methods of cytological diagnosis, and prognosis
      according to the stages at diagnosis. RESULTS: Two hundred cases with Stage 0 and
      stage I PDAC were reported from 14 institutions, which accounted for
      approximately 0.7% and 3% of all PDAC cases, respectively. Overall, 20% of the
      early-stage PDAC cases were symptomatic. Indirect imaging findings such as
      dilatation of the main pancreatic duct were useful to detect early-stage PDAC. In
      particular, local fatty changes may be specific to early-stage PDAC. For
      preoperative pathologic diagnosis, cytology during endoscopic retrograde
      cholangiopancreatography was more commonly applied than endoscopic ultrasound
      fine-needle aspiration. Although the overall prognosis was favorable, new PDAC
      lesions developed in the remnant pancreas in 11.5% cases. CONCLUSIONS: This
      multicenter study revealed several key points concerning the diagnosis and
      management of early-stage PDAC, including screening of asymptomatic cases,
      importance of indirect imaging findings, application of cytology during
      endoscopic retrograde cholangiopancreatography, and the risk of carcinogenesis in
      the remnant pancreas.

PMID- 29170052
TI  - Impact of age on survival of patients with pancreatic cancer after surgery:
      Analysis of SEER data.
AB  - BACKGROUND: To explore the impact of age on all-cause death and cancer-specific
      death in patients with pancreatic duct adenocarcinoma (PDAC) undergoing surgery.
      MATERIALS AND METHODS: Individuals with PDAC undergoing surgery between 2004 and
      2013 (N = 11,138) were retrospectively studied from the Surveillance,
      Epidemiology, and End Results (SEER) cancer registry database. The impact of age
      on all-cause death and cancer-specific death was assessed using Cox regression
      model and competing risk model respectively. RESULTS: Multivariate Cox regression
      analysis indicated that the risks of all-cause death increased with age: hazard
      ratios (95% confidence interval, 95%CI) were 1.10 (1.04-1.17), 1.31 (1.23-1.38),
      1.47 (1.35-1.61) for groups 61-70 years, 71-80 years, and >80 years,
      respectively, compared with <=60 years. Multivariate competing risk analysis
      indicated that the risk of cancer-specific death was similar between patients
      <=60 years and 61-70 years (subhazard ratio 0.93; 95% confidence interval 0.87
      1.00), but decreased in patients 71-80 years (subhazard ratio 0.84; 95%CI 0.79
      0.90) and >80 years (subhazard ratio 0.76; 95%CI 0.68-0.85). CONCLUSION: Age at
      diagnosis appeared to be an independent predictor of prognosis, with reverse
      impacts on all-cause death and cancer-specific death.

PMID- 29170053
TI  - A comparative study of pathophysiological alterations in scorpionism induced by
      Tityus serrulatus and Tityus bahiensis venoms.
AB  - Scorpionism is a relevant public health problem in several countries in tropical
      and subtropical regions. In Brazil, Tityus serrulatus sting can induce acute lung
      injury in part as a consequence of inflammation. Despite the occurrence of other
      scorpions of Tityus genus in Brazilian scorpiofauna, the knowledge regarding
      pulmonary alterations is related to T. serrulatus venom (Tsv). Here we studied,
      comparatively, the pathophysiological changes in the rat airways envenomed by Tsv
      or T. bahiensis venom (Tbv), since both scorpions are involved in human accidents
      but with severe envenomations occurring when victims are stung by T. serrulatus.
      After intravenous injection of the venoms (200 MUg/kg), both were able to induce
      Evans blue extravasation (in 30 min) into airways and increased protein
      extravasation into lungs at 4 and 24 h, but the magnitude of such events was
      higher in Tsv group. Hemorrhage (in 60 min) in the lungs was higher in Tbv group,
      while IL-1beta (at 1 h) and IL-6 (at 1 and 4 h) in lung homogenates were detected
      only in Tsv group. Four and 24 h after envenomation, myeloperoxidase activity in
      lung was equally augmented in the envenomed groups, as well as an increased in
      polymorphonuclear cell numbers in bronchoalveolar lavage fluid. At 4 h blood
      leukogram showed increased leukocyte values with the highest neutrophilia in Tsv
      group. The numbers of leukocytes and neutrophils remained higher than control at
      24 h in Tsv and Tbv groups, and it was accompanied by lympho (envenomed groups)
      and monocytosis (Tsv group). In conclusion, although Tbv was capable of inducing
      acute lung injury and blood leukocyte mobilization, most of the evaluated
      parameters were more affected by the Tsv. These results could help to explain the
      pathophysiology of the scorpionism and the clinical data arguing toward the
      greatest severity associated with T. serrulatus stings.

PMID- 29170054
TI  - Local and systemic effects of BdipTX-I, a Lys-49 phospholipase A2 isolated from
      Bothrops diporus snake venom.
AB  - The present work aimed to isolate a basic phospholipase A2 (PLA2) from Bothrops
      diporus snake venom (BdV), evaluate and compare the myotoxic and oedema-inducing
      activities, as well as the systemic effects caused by both the isolated PLA2 and
      BdV on Swiss mice. A Lys-49 PLA2 (BdipTX-I) was obtained through two
      chromatographic steps: an ion-exchange and a reverse phase. The local (oedema and
      myotoxicity) and systemic (hepatic and renal functions) effects were then
      assessed for BdipTX-I and BdV. Results showed that the oedema-inducing activity
      was significant in all tested doses (5 and 20 MUg/paw) for both BdipTX-I and BdV.
      Myotoxicity was evaluated by the increase of serum CK, CK-MB and LDH, and results
      showed that BdV effect is more prominent than BdipTX-I effect. The systemic
      effects were evaluated by determining specific laboratory markers: AST, ALT, GGT,
      ALP, urea, creatinine, protein and calcium. BdipTX-I and BdV were able to induce
      renal changes in the experimental model, leading to proteinuria (induced both by
      BdipTX-I and by BdV) and uremia (induced only by BdV). Thus, it is concluded that
      the systemic effects of BdV and BdipTX-I occur differently.

PMID- 29170055
TI  - Immune drug discovery from venoms.
AB  - This review catalogues recent advances in knowledge on venoms as standalone
      therapeutic agents or as blueprints for drug design, with an emphasis on venom
      derived compounds that affects the immune system. We discuss venoms and venom
      derived compounds that affect total immune cell numbers, immune cell
      proliferation, immune cell migration, immune cell phenotype and cytokine
      secretion. Identifying novel compounds that 'tune' the system, up-regulating the
      immune response during infectious disease and cancer and down-regulating the
      immune response during autoimmunity, will greatly expand the tool kit of human
      immunotherapeutics. Targeting these pathways may also open therapeutic options
      that alleviate symptoms of envenomation. Finally, combining recent advances in
      venomics with progress in low cost, high-throughput screening platforms will no
      doubt yield hundreds of prototype immune modulating compounds in the coming
      years.

PMID- 29170056
TI  - Choose Health: Food, Fun, and Fitness Youth Curriculum Promotes Positive
      Behaviors.
AB  - OBJECTIVE: Evaluate whether participation in Choose Health: Food, Fun, and
      Fitness (CHFFF), a hands-on, experiential curriculum aimed at third- to sixth
      graders, resulted in improvements in the targeted obesity and chronic disease
      prevention behaviors. METHODS: The researchers evaluated CHFFF in low-income
      youth participating in 2 federal programs in New York State during 2013-2015.
      Food and activity behaviors were assessed using the Expanded Food and Nutrition
      Education Program third- through fifth- and sixth- through eighth-grade pre-post
      surveys, along with 2 sets of added CHFFF-specific items completed by subsamples.
      Educators trained in CHFFF had youth complete the surveys as they delivered the
      curriculum, primarily in schools and after-school programs. RESULTS: Paired t
      tests showed significant (P < .01) positive changes before to after CHFFF
      education for consumption of vegetables, fruits, sweetened drinks, nutrition
      label reading, and other food and activity behaviors. CONCLUSIONS AND
      IMPLICATIONS: Results provide practice-based evidence that CHFFF promotes
      positive behavior change in participating youth.

PMID- 29170057
TI  - Barriers and Enablers to Implementation of Dietary Guidelines in Early Childhood
      Education Centers in Australia: Application of the Theoretical Domains Framework.
AB  - OBJECTIVE: To identify perceived barriers and enablers to implementation of
      dietary guidelines reported by early childhood education center cooks, and
      barriers and enablers associated with greater implementation based on assessment
      of center menu compliance. DESIGN: Cross-sectional telephone interview. SETTING:
      Early childhood education centers, New South Wales, Australia. PARTICIPANTS: A
      total of 202 cooks responsible for menu planning; 70 centers provided a menu for
      review of compliance with dietary guidelines. MAIN OUTCOME MEASURE: Barriers and
      enablers to dietary guideline implementation were determined using a tool
      assessing constructs of the Theoretical Domains Framework (TDF). Higher scores
      (>=6) for each construct indicated enablers to guideline implementation; lower
      scores (<6) suggested barriers. ANALYSIS: Multivariable linear regression
      identified TDF constructs associated with greater guideline implementation.
      RESULTS: Scores were lowest for reinforcement (mean, 5.85) and goals (mean, 5.89)
      domains, and highest for beliefs about consequences (mean, 6.51) and
      social/professional role and identity (mean, 6.50). The skills domain was
      positively associated with greater implementation of guidelines based on menu
      review (P = .01). CONCLUSIONS AND IMPLICATIONS: Cooks perceived
      social/professional role and identity, and beliefs about consequences to be
      enablers to dietary guideline implementation; however, only the skills domain was
      associated with greater implementation. There are opportunities to target the
      incongruence in perceptions vs reality of the barriers and enablers to
      implementation. Future research could examine the utility of the TDF to identify
      barriers and enablers to implementation to inform intervention development and
      for evaluating interventions to examine intervention mechanisms.

PMID- 29170058
TI  - Ability to Categorize Food Predicts Hypothetical Food Choices in Head Start
      Preschoolers.
AB  - OBJECTIVE: To investigate whether preschoolers are able to identify and
      categorize foods, and whether their ability to classify food as healthy predicts
      their hypothetical food choice. DESIGN: Structured interviews and body
      measurements with preschoolers, and teacher reports of classroom performance.
      SETTING: Six Head Start centers in a large southeastern region. PARTICIPANTS: A
      total of 235 preschoolers (mean age [SD], 4.73 [0.63] years; 45.4% girls).
      INTERVENTION(S): Teachers implemented a nutrition education intervention across
      the 2014-2015 school year in which children were taught to identify and
      categorize food as sometimes (ie, unhealthy) and anytime (ie, healthy). MAIN
      OUTCOME MEASURES: Preschooler responses to a hypothetical snack naming,
      classifying, and selection scenario. ANALYSIS: Hierarchical regression analyses
      to examine predictors of child hypothetical food selection. RESULTS: While
      controlling for child characteristics and cognitive functioning, preschoolers who
      were better at categorizing food as healthy or unhealthy were more likely to say
      they would choose the healthy food. Low-contrast food pairs in which food had to
      be classified based on multiple dimensions were outside the cognitive abilities
      of the preschoolers. CONCLUSIONS AND IMPLICATIONS: Nutrition interventions may be
      more effective in helping children make healthy food choices if developmental
      limitations in preschoolers' abilities to categorize food is addressed in their
      curriculum. Classification of food into evaluative categories is challenging for
      this age group. Categorizing on multiple dimensions is difficult, and dichotomous
      labeling of food as good or bad is not always accurate in directing children
      toward making food choices. Future research could evaluate further preschoolers'
      developmental potential for food categorization and nutrition decision making and
      consider factors that influence healthy food choices at both snack and mealtime.

PMID- 29170059
TI  - The clinical potential of adipogenesis and obesity-related microRNAs.
AB  - Obesity is a growing health problem commonly associated with numerous metabolic
      disorders including type 2 diabetes, hypertension, cardiovascular disease, and
      some forms of cancer. The burden of obesity and associated cardiometabolic
      diseases are believed to arise through complex interplay between genetics and
      epigenetics predisposition, nutrition, environment, and lifestyle. However, the
      molecular basis and the repertoire of obesity-affecting factors are still
      unknown. Emerging evidence is connecting microRNAs (miRNAs) dysregulation with
      adipogenesis and obesity. Alteration in miRNAs expression could result in changes
      in the pattern of genes controlling a range of biological processes including
      inflammation, lipid metabolism, insulin resistance and adipogenesis. Hence,
      understanding exact roles of miRNAs as well as the degree of their contribution
      to the regulation of adipogenesis and fat cell development in obesity would
      provide new therapeutic targets for the development of novel and effective anti
      obesity drugs. The objective of the current review is to: (i) discuss some of the
      latest development on relevant miRNAs dysregulation mainly in human adipogenesis
      and obesity, (ii) emphasize the role of circulating miRNAs as new promising
      therapeutics and attractive potential biomarkers for treating obesity and
      associated risk factor diseases, (iii) describe how dietary factors may influence
      obesity through modulation of miRNAs expression, (iv) highlight some of the
      actual limitations to the promise of miRNAs as novel therapeutics as well as to
      their translation for the benefit of patients, and finally (v) provide
      recommendations for future research on miRNA-based therapeutics that could lead
      to a breakthrough in the treatment of obesity and its associated pathologies.

PMID- 29170060
TI  - Low vitamin D status in relation to cardiovascular disease and mortality in
      Swedish women - Effect of extended follow-up.
AB  - BACKGROUND AND AIMS: The impact of vitamin D concentrations on subsequent
      cardiovascular disease (CVD) and overall mortality has been generally examined
      for periods under two decades. The magnitude of the association may depend on
      follow-up length. We aimed to investigate the relationship between baseline
      vitamin D and risk of total CVD, stroke and all-cause mortality over three
      decades of follow-up. Secondly, we aimed to assess how follow-up affects the
      associations. METHODS AND RESULTS: Concentrations of 25-hydroxyvitamin D (25D)
      were measured in a population-based sample of 1227 middle-aged women using serum
      collected at baseline and categorized into low (lowest 25D quartile) vs high 25D
      status (upper three 25D quartiles). Hazard ratio (HR) of the endpoints was
      estimated for low 25D. The impact of follow-up was examined in intermediary
      analyses where follow-up was interrupted up to four times, each time decreasing
      it by five years. There were 596 cardiovascular events and 635 participants died.
      During the first 17 years, the low 25D group experienced a 29% higher CVD risk
      and 3.3-fold higher stroke risk after accounting for confounders. Longer follow
      up diminished significantly these risks and 25D status had no contribution at 32
      years. For mortality, the decline over time was less dramatic, with HR = 1.96
      (1.25; 3.08) at 17 years and HR = 1.42 (1.17; 1.72) at 37 years. CONCLUSION: Low
      25D status increased the risk for all endpoints, but a lengthy follow-up
      diminished these risks towards the null. The impact of follow-up depends on the
      outcome. Future studies of 25D and disease should use repeated 25D assessments.

PMID- 29170061
TI  - The association between muscle mass deficits and arterial stiffness in middle
      aged men.
AB  - BACKGROUND AND AIMS: Early diagnosis of arteriosclerosis is fundamental for the
      prevention of cardiovascular morbidity and mortality. The current study was
      performed to identify major predictors of arteriosclerosis and to assess the
      association between arterial stiffness as measured by cardio-ankle vascular index
      (CAVI) and muscle mass deficit (MMD) estimated by bioelectrical impedance
      analysis (BIA) in middle-aged men. METHODS AND RESULTS: Data were gathered from
      3356 middle-aged men who visited a health promotion center. CAVI was measured as
      an index of arterial stiffness. Body composition analysis was performed using
      BIA. MMD was positively associated with CAVI in the regression model. The odds
      ratios for high-CAVI (>=9.0) rose with MMD grade in a dose-dependent manner after
      adjusting for age, lifestyle factors and current medication use. The estimated
      mean CAVI rose as MMD grade increased (P for trend >0.001). CONCLUSIONS: MMD
      estimated from BIA was positively associated with arterial stiffness in middle
      aged men. These findings show a close interaction between low muscle mass and
      cardiovascular risk.

PMID- 29170062
TI  - The relationship between high-density lipoprotein cholesterol levels and arterial
      stiffness in a Taiwanese population.
AB  - BACKGROUND AND AIMS: There are few studies on the association between HDL-C
      levels and arterial stiffness (AS). HDL-C levels vary in males and females, and
      it is not clear whether the relationship between HDL-C levels and AS is
      influenced by gender. The purpose of this study was to investigate gender
      differences in the association between HDL-C levels and AS in adults. METHODS AND
      RESULTS: After excluding subjects using lipid-lowering agent, 7254 subjects were
      enrolled. The AS was assessed by measuring the brachial-ankle pulse wave velocity
      (baPWV) value. The quartiles of HDL-C were <38, 38-45, 45-53 and >53 mg/dL in men
      and <48, 48-57, 57-69 and >68 mg/dL in women, respectively. In subjects aged <50
      years, none of the HDL-C quartiles were associated with baPWV values. In subjects
      aged >=50 years, the highest quartile of HDL-C (beta: -37.57, 95% CI: -61.61 to 
      13.54) was negatively related to baPWV values. When considering gender difference
      in subjects aged >=50 years, the highest quartile of HDL-C (Q4 beta: -57.22, 95%
      CI: -95.63 to -18.81) was inversely associated with baPWV values in women, but
      none of the HDL-C quartiles were related to baPWV values in men. CONCLUSIONS: A
      high HDL-C level was associated with a lower risk of AS in subjects aged >=50
      years in women but not in men, although this relationship was not apparent in
      subjects aged <50 years. The association between HDL-C level and AS is thus
      influenced by gender in people aged >=50 years.

PMID- 29170064
TI  - The role of paraoxonase in cancer.
AB  - The paraoxonase (PON) gene family includes three proteins, PON1, PON2 and PON3.
      PON1 and PON3 are both associated with high-density lipoprotein (HDL) particles
      and exert anti-oxidant and anti-inflammatory properties. PON2 and PON3 are
      intracellular enzymes which modulate mitochondrial superoxide anion production
      and endoplasmic reticulum (ER) stress-induced apoptosis. The pleiotropic roles
      exerted by PONs have been mainly investigated in cardiovascular and
      neurodegenerative diseases. In recent years, overexpression of PON2 and PON3 has
      been observed in cancer cells and it has been proposed that both enzymes could be
      involved in tumor survival and stress resistance. Moreover, a lower activity of
      serum PON1 has been reported in cancer patients. This review summarizes
      literature data on the role of PONs in human cancers and their potential role as
      a target for antitumor drugs.

PMID- 29170063
TI  - Incidence and progression of Parvovirus B19 infection and molecular changes in
      circulating B19V strains in children with haematological malignancy: A follow up
      study.
AB  - The present study was planned to estimate the incidence of human Parvovirus B19
      infection and understand its progression in children suffering with hematological
      malignancy. The circulating B19V genotypes and viral mutations occurring in
      strains of B19V over one-year period were also studied. Children with
      malignancies were enrolled consecutively and were followed up for one-year
      period. Serum sample was collected at the time of enrolment and each follow up
      visit and was tested for anti B19V IgG and IgM as well as for B19V DNA. At least
      one B19V DNA positive sample from each patient was processed for sequencing. For
      patients positive for B19V DNA >1 time and at least 6 months apart, last positive
      sample from the same patient was also sequenced to study the nucleotide change
      over time. We have found very high incidence of B19V infection (100%) in the
      study population. All the patients tested positive for at least one B19V
      infection parameter (either antibodies or DNA) at least once, over one year of
      follow up. Cumulative percent positivity of anti B19V IgG, anti B19V IgM and B19V
      DNA was 85.3%, 45.2% and 72.1% respectively. Genotype 3b was reported, with
      occasional nucleotide change over one year period. DNA clearance was delayed in
      spite of appearance of IgG antibodies. Appearance of IgM class of antibodies was
      either delayed or absent. To conclude, children with haematological malignancies
      have high incidence of B19V infection with late and short lived serological
      response and persistence of DNA for long duration.

PMID- 29170065
TI  - Challenges in Ras therapeutics in pancreatic cancer.
AB  - Pancreatic cancer is considered among the most aggressive and the least curable
      of all human malignancies. It is usually characterized by multiple aberrations in
      tumor suppressor genes and oncogenes, most notably activating mutations in KRAS.
      This review examines the various attempts that have been made to inhibit Kras and
      its downstream signaling pathways in pancreatic cancer with an emphasis on
      challenges related to clinical trials. Attempts include preventing the
      localization of Ras protein to the plasma membrane, inhibiting downstream
      oncogenic signaling by targeting Kras effectors such as MEK1/2, Erk1/2 or Akt
      singly or in combination, and directly inhibiting Kras protein. Most clinical
      trials have focused on inhibiting downstream effector pathways and clinical
      benefit has been limited due to compensatory mechanisms and toxicity associated
      with small therapeutic windows. Additionally, genetic screens have been conducted
      to identify gene or genes that could provide therapeutic vulnerabilities in
      mutant KRAS cells and provide a way to target mutant Kras protein only. We also
      discuss how potentially transforming clinical trials have failed in the past and
      what new strategies are on-going in clinical trials for pancreas cancer. For long
      term success in targeting Kras, future efforts should focus on combinatorial
      strategies to more effectively block Kras pathways at multiple points, and
      improve translational application of pre-clinical data to the clinic.

PMID- 29170066
TI  - Glioma epigenetics: From subclassification to novel treatment options.
AB  - Gliomas are the most common malignant primary brain tumors, of which glioblastoma
      is the most malignant form (WHO grade IV), and notorious for treatment
      resistance. Over the last decade mutations in epigenetic regulator genes have
      been identified as key drivers of subtypes of gliomas with distinct clinical
      features. Most characteristic are mutations in IDH1 or IDH2 in lower grade
      gliomas, and histone 3 mutations in pediatric high grade gliomas that are also
      associated with characteristic DNA methylation patterns. Furthermore, in adult
      glioblastoma patients epigenetic silencing of the DNA repair gene MGMT by
      promoter methylation is predictive for benefit from alkylating agent therapy.
      These epigenetic alterations are used as biomarkers and play a central role for
      classification of gliomas (WHO 2016) and treatment decisions. Here we review the
      pivotal role of epigenetic alterations in the etiology and biology of gliomas. We
      summarize the complex interactions between "driver" mutations, DNA methylation,
      histone post-translational modifications, and overall chromatin organization, and
      how they inform current efforts of testing epigenetic compounds and combinations
      in preclinical and clinical studies.

PMID- 29170067
TI  - Perspectives on the integration of Immuno-Oncology Biomarkers and drugs in a
      Health Care setting.
AB  - Immunotherapies, specifically checkpoint inhibitors, are becoming an important
      component in cancer care with the most application now in melanoma and lung
      cancer patients. Some drawbacks that converge with this new evolution are the
      rather low response rates to these drugs and their high cost with a significant
      economic impact on the health care system. These major challenges can likely be
      circumvented by implementing a "personalized immuno-oncology" approach to
      accomplish a selection of optimal responders based on biomarkers. In this paper
      we first discuss the legal framework for the development of valuable in vitro
      diagnostics. Based on a case study in lung cancer, the clinical validity and
      utility requirements of predictive immuno-oncology biomarkers is highlighted and
      an overview is given on the evolution towards multiplex or omics-based assays
      together with its challenges and pitfalls. Finally, some initiatives between the
      public and private sector are pinpointed to sustain the future access to
      innovative medicines in cancer therapy at a reasonable cost.

PMID- 29170068
TI  - Enhanced heat tolerance in transgenic silkworm via overexpression of Pyrococcus
      furiosus superoxide reductase.
AB  - Heat shock causes a serious harm to organisms by accelerating the production of
      reactive oxygen species (ROS). Pyrococcus furiosus superoxide reductase (PfSOR)
      is an enzyme that efficiently detoxifies ROS. In order to generate a silkworm
      strain with high heat tolerance for sericulture, we synthesized an artificial DNA
      sequence encoding PfSOR based on the codon bias of Bombyx mori. PfSOR was
      successfully overexpressed in transgenic silkworm (named A4SOR) and BmE cells, as
      determined by RT-PCR and western blot analyses. An SOR activity assay confirmed
      that the expressed enzyme was functional in A4SOR. After exposure to a
      temperature of 35  degrees C for 44 h, the mortality rate was about 30% lower in
      transgenic A4SOR than in non-transgenic silkworms. Moreover, transgene expression
      had no apparent effect on economic characteristics of silkworms. The heat
      tolerance of silkworm was thus enhanced by expressing an archaeal SOR; this can
      be useful for sericulture in regions where the average temperature exceeds the
      optimal environmental temperature for B. mori of 25  degrees C.

PMID- 29170070
TI  - Dynamic phase alignment of ongoing auditory cortex oscillations.
AB  - Neural oscillations can synchronize to external rhythmic stimuli, as for example
      in speech and music. While previous studies have mainly focused on elucidating
      the fundamental concept of neural entrainment, less is known about the time
      course of entrainment. In this human electroencephalography (EEG) study, we
      unravel the temporal evolution of neural entrainment by contrasting short and
      long periods of rhythmic stimulation. Listeners had to detect short silent gaps
      that were systematically distributed with respect to the phase of a 3 Hz
      frequency-modulated tone. We found that gap detection performance was modulated
      by the stimulus stream with a consistent stimulus phase across participants for
      short and long stimulation. Electrophysiological analysis confirmed neural
      entrainment effects at 3 Hz and the 6 Hz harmonic for both short and long
      stimulation lengths. 3 Hz source level analysis revealed that longer stimulation
      resulted in a phase shift of a participant's neural phase relative to the
      stimulus phase. Phase coupling increased over the first second of stimulation,
      but no effects for phase coupling strength were observed over time. The dynamic
      evolution of phase alignment suggests that the brain attunes to external rhythmic
      stimulation by adapting the brain's internal representation of incoming
      environmental stimuli.

PMID- 29170069
TI  - A common neural network differentially mediates direct and social fear learning.
AB  - Across species, fears often spread between individuals through social learning.
      Yet, little is known about the neural and computational mechanisms underlying
      social learning. Addressing this question, we compared social and direct
      (Pavlovian) fear learning showing that they showed indistinguishable behavioral
      effects, and involved the same cross-modal (self/other) aversive learning
      network, centered on the amygdala, the anterior insula (AI), and the anterior
      cingulate cortex (ACC). Crucially, the information flow within this network
      differed between social and direct fear learning. Dynamic causal modeling
      combined with reinforcement learning modeling revealed that the amygdala and AI
      provided input to this network during direct and social learning, respectively.
      Furthermore, the AI gated learning signals based on surprise (associability),
      which were conveyed to the ACC, in both learning modalities. Our findings provide
      insights into the mechanisms underlying social fear learning, with implications
      for understanding common psychological dysfunctions, such as phobias and other
      anxiety disorders.

PMID- 29170071
TI  - Cortical networks for auditory detection with and without informational masking:
      Task effects and implications for conscious perception.
AB  - Ambiguous and masked stimuli have been used to study conscious perception by
      comparing neural activity during different percepts of identical physical
      stimuli. One limitation of this approach is that it typically requires a
      reporting task that may engage neural processes beyond those required for
      conscious perception. Here, we explored potential fMRI correlates of auditory
      conscious perception with and without overt report. In experiment 1, regular tone
      patterns were presented as targets under informational masking, and participants
      reported their percepts on each trial. In experiment 2, regular tone patterns
      were presented without masking, while the uninformed participants (i) passively
      fixated, (ii) performed an orthogonal visual task, and (iii) reported trial-wise
      the presence of the auditory pattern as in experiment 1 (in fixed order). Under
      informational masking, target-pattern detection was associated with activity in
      auditory cortex, superior temporal sulcus, and a distributed fronto-parieto
      insular network. Unmasked and task-irrelevant tone patterns elicited activity
      that overlapped with the network observed under informational masking in auditory
      cortex, the right superior temporal sulcus, and the ventral precentral sulcus in
      an ROI analysis. We therefore consider these structures candidate regions for a
      neural substrate of auditory conscious perception. In contrast, activity in the
      intraparietal sulcus, insula, and dorsal precentral sulcus were only observed for
      unmasked tone patterns when they were task relevant. These areas therefore appear
      more closely related to task performance or top-down attention rather than
      auditory conscious perception, per se.

PMID- 29170072
TI  - Pancreatic enzyme replacement therapy after gastric resection: An update.
AB  - Exocrine pancreatic insufficiency (EPI) is one of the possible mechanisms of fat
      maldigestion following gastric surgery, together with reduced food intake, loss
      of gastric reservoir, small bowel bacterial overgrowth and rapid small bowel
      transit. Oral pancreatic enzyme replacement therapy (PERT) is the mainstay of
      treatment for EPI. The efficacy and safety of pancreatic enzyme substitution in
      patients following gastric resection remains unclear. This review article
      summarizes relevant studies addressing PERT after gastric resection.

PMID- 29170073
TI  - Effect of intravenous fentanyl on ticagrelor absorption and platelet inhibition
      among patients undergoing percutaneous coronary intervention: Design, rationale,
      and sample characteristics of the PACIFY randomized trial.
AB  - INTRODUCTION: Morphine reduces and delays the absorption of oral P2Y12 platelet
      inhibitors. Fentanyl is another opiate often administered during percutaneous
      coronary interventions (PCI). The PACIFY study will test whether intravenous
      fentanyl also impairs the absorption and action of oral P2Y12 inhibitors.
      METHODS: PACIFY is a single-center trial randomizing adults undergoing clinically
      indicated coronary angiography to have the procedure with or without fentanyl.
      All patients will receive local anesthetic and intravenous midazolam. Doses of
      all drugs are at the discretion of treating providers. Patients that require PCI
      receive 180mg of oral ticagrelor during the angiography procedure. The primary
      outcome is area under the ticagrelor plasma concentration-time curve. Secondary
      outcomes include platelet inhibition 2-h after loading, measured both by
      VerifyNow(r) (Accriva Diagnostics, San Diego, California) and by light
      transmission platelet aggregometry. We will also survey patient comfort and
      measure high-sensitivity troponin levels. Patients and outcomes assessors are
      blinded, treating providers are not. RESULTS: A total of 212 patients are
      participating, 70 of whom required PCI. Baseline characteristics are numerically
      well balanced in both study arms. Mean age is 63years and 27% are female. There
      were no differences in total midazolam dose during the index PCI procedure,
      whereas mean total fentanyl dose was 9 mcg in the no-fentanyl arm (2 participants
      in this arm required fentanyl for bailout treatment of pain) versus 96 mcg in the
      fentanyl arm. CONCLUSIONS: This study will provide important information on the
      impact of fentanyl administered during PCI on the absorption of ticagrelor and
      its antiplatelet activity. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT02683707.

PMID- 29170074
TI  - Study design considerations for the Standardized Treatment of Pulmonary
      Exacerbations 2 (STOP2): A trial to compare intravenous antibiotic treatment
      durations in CF.
AB  - BACKGROUND: Pulmonary exacerbations (PEx) in cystic fibrosis (CF) are common and
      contribute to morbidity and mortality. Duration of IV antibiotic therapy to treat
      PEx varies widely in the US, and there are few data to guide treatment decisions.
      METHODS: We combined a survey of CF stakeholders with retrospective analyses of a
      recent observational study of CF PEx to design a multicenter, randomized,
      prospective study comparing the efficacy and safety of different durations of IV
      antibiotics for PEx to meet the needs of people with CF and their caregivers.
      RESULTS: IV antibiotic duration was cited as the most important PEx research
      question by responding CF physicians and top concern among surveyed CF
      patients/caregivers. During PEx, forced expiratory volume in 1s (FEV1% predicted)
      and symptom responses at 7-10days of IV antibiotics identified two distinct
      groups: early robust responders (ERR) who subsequently experienced greater FEV1
      improvements compared to non-ERR (NERR). In addition to greater FEV1 and symptom
      responses, only 14% of ERR patients were treated with IV antibiotics for >15days,
      compared with 45% of NERR patients. CONCLUSIONS: A divergent trial design that
      evaluates subjects' interim improvement in FEV1 and symptoms to tailor
      randomization to IV treatment duration (10 vs. 14days for ERR, 14 vs. 21days for
      NERR) may alleviate physician and patient concerns about excess or inadequate
      treatment. Such a study has the potential to provide evidence necessary to
      standardize IV antibiotic duration in CF PEx care -a first step to conducting PEx
      research of other treatment features.

PMID- 29170075
TI  - Reducing depressive symptoms through behavioral activation in churches: A Hybrid
      2 randomized effectiveness-implementation design.
AB  - : Rural African Americans are disproportionately exposed to numerous stressors
      such as poverty that place them at risk for experiencing elevated levels of
      depressive symptoms. Effective treatments for decreasing depressive symptoms
      exist, but rural African Americans often fail to receive adequate and timely
      care. Churches have been used to address physical health outcomes in rural
      African American communities, but few have focused primarily on addressing mental
      health outcomes. Our partnership, consisting of faith community leaders and
      academic researchers, adapted an evidence-based behavioral activation
      intervention for use with rural African American churches. This 8-session
      intervention was adapted to include faith-based themes, Scripture, and other
      aspects of the rural African American faith culture (e.g. bible studies) This
      manuscript describes a Hybrid-II implementation trial that seeks to test the
      effectiveness of the culturally adapted evidence-based intervention (Renewed and
      Empowered for the Journey to Overcome in Christ: REJOICE) and gather preliminary
      data on the strategies necessary to support the successful implementation of this
      intervention in 24 rural African American churches. This study employs a
      randomized one-way crossover cluster design to assess effectiveness in reducing
      depressive symptoms and gather preliminary data regarding implementation
      outcomes, specifically fidelity, associated with 2 implementation strategies:
      training only and training+coaching calls. This project has the potential to
      generate knowledge that will lead to improvements in the provision of mental
      health interventions within the rural African American community. Further, the
      use of the Hybrid-II design has the potential to advance our understanding of
      strategies that will support the implementation of and sustainability of mental
      health interventions within rural African American faith communities. TRIAL
      REGISTRATION: NCT02860741. Registered August 5, 2016.

PMID- 29170076
TI  - Association of interleukin-6 with aortic stiffness in end-stage renal disease.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality in patients with
      chronic kidney disease (CKD). Aortic stiffness, a nontraditional risk factor, is
      associated with high rate of mortality in CKD. Using a CKD animal model with
      medial vascular calcification, we previously reported increased mRNA expression
      of interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-1beta (IL
      1beta) in calcified aorta. The aim of the study was to investigate the
      association between IL-6, TNF, IL-1beta, and aortic stiffness in end-stage renal
      disease patients. In a cross-sectional study, we enrolled 351 patients on
      dialysis. Aortic stiffness was assessed by carotid-femoral pulse wave velocity
      (cf-PWV), while central pulse pressure and augmentation index were assessed using
      generalized transfer function applied to the radial artery pressure wave form.
      Plasma IL-6, TNF, and IL-1beta were measured by enzyme-linked immunosorbent
      assay. IL-6 was associated with cf-PWV adjusted for mean blood pressure (MBP)
      (standardized beta = 0.270; P < .001). In a multivariate adjusted model for age,
      diabetes, hypertension, CVD, and MBP, IL-6 was still associated with cf-PWV
      (standardized beta = 0.096; P = .026). The impact of age, diabetes, and CVD on cf
      PWV was partially mediated by IL-6 in a mediation analysis. However, there were
      no associations between TNF, IL-1beta, and aortic stiffness. While IL-6 was
      associated with augmentation index (standardized beta = 0.224; P < .001) and
      central pulse pressure (standardized beta = 0.162; P = .001) when adjusted for
      MBP and heart rate, this relationship was not significant after adjusting for
      potential confounders.This study suggests a potential role of IL-6 for CKD
      related aortic stiffness.

PMID- 29170077
TI  - 5 years after introduction of a transition protocol: An evaluation of transition
      care for patients with chronic bladder conditions.
AB  - INTRODUCTION: In recent years, more attention has been given to the transition of
      adolescents in urological care. In 2010, the current team investigated the needs
      of children with chronic bladder conditions, in preparation for transfer to adult
      care. A transition protocol was developed and implemented. The current study
      evaluated current transition care, in order to further improve the transition
      process. OBJECTIVE: To give insight into the current transition care of
      adolescents with chronic bladder conditions since the introduction of a
      transition protocol in 2011. STUDY DESIGN: A total of 124 patients with chronic
      bladder conditions, born 1980-2003, received a questionnaire. The study
      population was divided in a pre-transfer (n = 97) and post-transfer group (n =
      27). The questionnaire was based on that used for a national study and was
      supplemented with specific urological questions. The questions for the pre
      transfer patients investigated their level of independence, what subjects were
      discussed with the healthcare professionals, and their expectations and wishes
      regarding transfer to adult urology care. The post-transfer group was asked for
      their opinions about their transfer process. RESULTS: A total of 61% (n = 76/124)
      responded (pre-transfer 61/97 patients and post-transfer 1527 patients). Their
      knowledge about their condition and related issues was generally good. The
      subjects 'future', 'relationships', 'sexuality' and 'fertility' were discussed
      more with the nurse practitioner than with the pediatric urologist in comparison
      with 2010. The last three subjects were only discussed with one third of the
      adolescents (Summary table). The bond with the pediatric urologist was the most
      common reason to continue care at the Pediatric Urology department. Adolescents
      aged >18 years were better prepared for transfer to adult urology than in 2010.
      The majority of the post-transfer patients were transferred because of being aged
      >17 years. Most patients in the post-transfer group were pleased with the current
      transition process. DISCUSSION: The results showed that changes occurred after
      implementation of the personal patient transition protocol. The mean age of the
      pre-transfer group was younger compared to 2010; this influenced some of the
      results. Therefore, they were divided into two age groups, for more reliable
      outcomes. More attention to subjects like relationships and sexuality could
      further improve the satisfaction of adolescents in transition. CONCLUSION: The
      older adolescents seemed better prepared for their transfer from pediatric to
      adult urology than in 2010. The majority was satisfied with the current
      transition protocol. Tailor-made transition care seemed to be the best option.

PMID- 29170078
TI  - How common is substantial weight gain after pregnancy?
AB  - BACKGROUND: Although population-based studies indicate that on average, women
      gain 1-2kg between pregnancies, women with obesity often attribute its
      development to childbearing. There is little contemporary data available
      regarding how commonly this occurs, particularly in women of different body mass
      index (BMI) categories. The aim of this study was to examine inter-pregnancy
      weight changes among women at a tertiary obstetric hospital in Melbourne,
      Australia. METHODS: This was a retrospective review of data from the Birthing
      Outcomes System electronic record of 19,617 women aged 20 years or older, who
      delivered at least two consecutive singleton infants at >=37 weeks' gestation at
      Mercy Hospital for Women between December 1994 and December 2015. A logistic
      regression model was used to assess the relationship between gain of >=4kg/m2
      between pregnancies and maternal BMI category in the first pregnancy, adjusting
      for covariates of maternal age, inter-pregnancy interval, and socioeconomic
      status. RESULTS: Gain of >=4kg/m2 between the first two pregnancies occurred in
      7.5% of normal weight women, 10.5% of overweight women, and 13.4% of women with
      obesity. One in five women who were normal weight in their first pregnancy
      increased to overweight or obese BMI categories in their second pregnancy.
      CONCLUSIONS: Substantial weight gain in relation to pregnancy affects a
      considerable proportion of women. Since inter-pregnancy weight gain is associated
      with several complications in the next pregnancy and longer term, avoiding
      excessive weight gain during and between pregnancies may prevent adverse health
      consequences in mothers and offspring.

PMID- 29170079
TI  - Practical management of behavioral problems in mucopolysaccharidoses disorders.
AB  - The mucopolysaccharidosis (MPS) disorders are caused by deficiencies of specific
      lysosomal enzymes, resulting in progressive glycosaminoglycan (GAG) accumulation
      in cells and tissues throughout the body. Excessive GAG storage can lead to a
      variety of somatic manifestations as well as primary and secondary neurological
      symptoms. Behavioral problems (like hyperactivity, attention difficulties, and
      severe frustration) and sleeping problems are typical primary neurological
      symptoms of MPS caused by GAG accumulation in neurons, and are frequently
      observed in patients with MPS I, II, III, and VII. As these problems often place
      a significant burden on the family, proper management is important. This review
      summarizes current insights into behavioral and sleeping problems in MPS
      disorders and the most optimal management approaches, as presented and discussed
      during a meeting of an international group of experts with extensive experience
      in managing and treating MPS.

PMID- 29170080
TI  - Epilepsy in mucopolysaccharidosis disorders.
AB  - The mucopolysaccharidosis (MPS) disorders are caused by deficiencies of specific
      lysosomal enzymes involved in the catabolism of glycosaminoglycans (GAGs). The
      resulting GAG accumulation in cells and tissues throughout the body leads to
      progressive multi-organ dysfunction. MPS patients present with several somatic
      manifestations, including short stature, musculoskeletal abnormalities, and
      cardiorespiratory dysfunction, and several primary and secondary neurological
      signs and symptoms. Epileptic seizures are neurological signs of MPS thought to
      develop due to accumulation of GAGs in the brain, triggering alterations in
      neuronal connectivity and signaling, and release of inflammatory mediators. The
      amount of literature on the prevalence, pathophysiology, clinical features, and
      management of epileptic seizures in patients with MPS is limited. This review
      discusses current knowledge on this topic, as well as two case examples,
      presented and discussed during a closed meeting on MPS and the brain among an
      international group of experts with extensive experience in managing and treating
      MPS.

PMID- 29170081
TI  - Symptomatic benign distal biliary stricture in the setting of anomalous
      pancreaticobiliary junction treated with metal biliary and temporary plastic
      pancreatic stents.

PMID- 29170082
TI  - Spiral valves of Heister as visualized by direct cystic ductoscopy.

PMID- 29170083
TI  - Successful repair of duodenal perforation with endoscopic vacuum therapy.

PMID- 29170084
TI  - Serum anti-TOPO48 autoantibody as a biomarker for early diagnosis and prognosis
      in patients with esophageal squamous cell carcinoma.
AB  - BACKGROUND AND AIM: We previously reported a novel tumor associated antigen (TTA)
      with molecular weight around 48kDa that is a fragment derived from human DNA
      topoiomerase I (TOP1). We termed the novel TAA as TOPO48 and termed autoantibody
      against the TAA as anti-TOPO48 autoantibody. The aim of this study is to further
      investigate the clinical applications of the autoantibody in patients with
      esophageal squamous cell carcinomas (ESCC). METHODS: Serum levels of the anti
      TOPO48 autoantibody in 112 ESCC patients, 112 age- and gender-matched healthy
      controls and 75 patients with esophageal benign tumors were determined by using a
      specific anti-TOPO48 autoantibody ELISA. Then, we statistically evaluated its
      clinical significance. RESULTS: We found that serum anti-TOPO48 autoantibody
      levels in ESCC patients were significantly higher than that in healthy controls
      and benign tumor patients (P=0.001). The percentage of sera with a positive level
      of anti-TOPO48 autoantibody in early stages was significantly higher than that in
      advanced stages of the cancer patients when the maximum level of healthy control
      sera was taken as a cut-off value (P=0.001). The area under ROC curve was 0.863
      (95% CI=0.797-0.928) for healthy controls vs. early stage ESCC. In addition,
      patients with positive anti-TOPO48 autoantibody had significantly higher survival
      rate and longer survival time than that with negative anti-TOPO48 autoantibody in
      cancer patients (P=0.038, 0.025 and 0.047 for all stages, early stage and
      advanced stage, respectively). CONCLUSIONS: Our results suggest that anti-TOPO48
      autoantibody may be a potentially useful biomarker for early diagnosis and
      prognosis of ESCC.

PMID- 29170085
TI  - Modelling studies determing the mode of action of anthelmintics inhibiting in
      vitro trehalose-6-phosphate phosphatase (TPP) of Anisakis simplex s.l.
AB  - The trehalose-6-phosphate phosphatase (TPP) enzyme is involved in the synthesis
      of trehalose, the main sugar in the energy metabolism of nematodes. TPP is a
      member of the HAD-like hydrolase superfamily and shows a robust and specific
      phosphatase activity for the substrate trehalose-6-phosphate. The presence of
      conserved active sites of TPP in closely related nematodes and its absence in
      humans makes it a promising target for antiparasitic drugs. In the present study,
      homology modeling, molecular docking and MD simulation techniques were used to
      explore the structure and dynamics of TPP. In the active site, a magnesium ion is
      stabilized by 3 coordinate bonds formed by D189, D191 and D400. The key amino
      acids involved in ligand binding by the enzyme are C198, Y201,T357, D191 and
      Y197. This study relied on docking to select potential inhibitors of TPP which
      were tested in vitro for sensitivity to anthelmintic drugs such as levamisole and
      ivermectin targeting Anisakis simplex. The higher toxicity of LEV than IVM was
      demonstrated after 96 h, 30% of larvae were motile in cultures with 100 MUg/ml of
      LEV and 1000 MUg/ml of IVM. We identified drug combination of LEV-IVM against in
      vitro A. simplex as agonistic effect (CI = 1.1). Levamisole appeared to be a more
      effective drug which inhibited enzyme activity after 48 h and expression of mRNA
      after 96 h at a concentration of 10 MUg/ml. This preliminary study predicted the
      structure of TPP, and the results of an in vitro experiment involving A. simplex
      will contribute to the development of effective inhibitors with potential
      antiparasitic activity in the future.

PMID- 29170086
TI  - Toxoplasma gondii-positive human sera recognise intracellular tachyzoites and
      bradyzoites with diverse patterns of immunoreactivity.
AB  - Antibody detection assays have long been the first line test to confirm infection
      with the zoonotic parasite Toxoplasma gondii. However, challenges exist with
      serological diagnosis, especially distinguishing between acute, latent and
      reactivation disease states. The sensitivity and specificity of serological tests
      might be improved by testing for antibodies against parasite antigens other than
      those typically found on the parasite surface during the acute stage. To this
      end, we analysed the reactivity profile of human sera, identified as positive for
      anti-Toxoplasma gondii IgG in traditional assays, by indirect immunofluorescence
      reactivity to acute stage intracellular tachyzoites and in vitro-induced latent
      stage bradyzoites. The majority of anti-Toxoplasma gondii IgG positive sera
      recognised both intracellularly replicating tachyzoites and in vitro-induced
      bradyzoites with varying patterns of immune-reactivity. Furthermore, anti
      bradyzoite antibodies were not detected in sera that were IgM-positive/IgG
      negative. These results demonstrate that anti-Toxoplasma gondii-positive sera may
      contain antibodies to a variety of antigens in addition to those traditionally
      used in serological tests, and suggest the need for further investigations into
      the utility of anti-bradyzoite-specific antibodies to aid in diagnosis of
      Toxoplasma gondii infection.

PMID- 29170087
TI  - Avian malaria infection intensity influences mosquito feeding patterns.
AB  - Pathogen-induced host phenotypic changes are widespread phenomena that can
      dramatically influence host-vector interactions. Enhanced vector attraction to
      infected hosts has been reported in a variety of host-pathogen systems, and has
      given rise to the parasite manipulation hypothesis whereby pathogens may
      adaptively modify host phenotypes to increase transmission from host to host.
      However, host phenotypic changes do not always favour the transmission of
      pathogens, as random host choice, reduced host attractiveness and even host
      avoidance after infection have also been reported. Thus, the effects of hosts'
      parasitic infections on vector feeding behaviour and on the likelihood of
      parasite transmission remain unclear. Here, we experimentally tested how host
      infection status and infection intensity with avian Plasmodium affect mosquito
      feeding patterns in house sparrows (Passer domesticus). In separate experiments,
      mosquitoes were allowed to bite pairs containing (i) one infected and one
      uninfected bird and (ii) two infected birds, one of which treated with the
      antimalarial drug, primaquine. We found that mosquitoes fed randomly when exposed
      to both infected and uninfected birds. However, when mosquitoes were exposed only
      to infected individuals, they preferred to bite the non-treated birds. These
      results suggest that the malarial parasite load rather than the infection itself
      plays a key role in mosquito attraction. Our findings partially support the
      parasite manipulation hypothesis, which probably operates via a reduction in
      defensive behaviour, and highlights the importance of considering parasite load
      in studies on host-vector-pathogen interactions.

PMID- 29170088
TI  - Simplified medical abortion screening: a demonstration project.
AB  - OBJECTIVES: The objectives were to evaluate the safety and acceptability of
      outpatient medical abortion in selected women without a pretreatment ultrasound
      or pelvic examination. STUDY DESIGN: We conducted a prospective case-series study
      to estimate the incidence of serious adverse events (death, life-threatening
      event, hospitalization, transfusion or any other medical problem that we judged
      to be significant), surgical completion of the abortion and satisfaction in women
      provided with medical abortion without a pretreatment ultrasound or pelvic
      examination. We enrolled 406 women requesting medical abortion in Moldova, Mexico
      and the United States. To be eligible, a woman must have been certain that her
      last menstrual period started within the prior 56days, have had regular menses
      before the pregnancy, not have used hormonal contraceptives in the prior 2months
      (in the United States and Mexico) or 3months (in Moldova), have no risk factors
      for or symptoms of ectopic pregnancy, and not have had an ultrasound or pelvic
      exam in this pregnancy. One site also excluded women with uterine enlargement on
      abdominal palpation. Each participant received mifepristone (200mg orally) and
      misoprostol (400 mcg sublingually in Moldova; 800 mcg buccally at all other
      sites) and was followed until complete abortion, defined as requiring no further
      treatment. RESULTS: Of the 365 (90%) participants who provided sufficient follow
      up information for analysis, 347 (95%) had complete abortion without additional
      treatment, 5 (1%) had surgical aspiration, and 10 (3%) had extra misoprostol.
      Three participants (1%) had serious adverse events; these included two hospital
      admissions for heavy bleeding managed with aspiration and one diagnosis of
      persistent gestational sac 19days after enrollment. Most (317, 90%) participants
      were pleased with omitting the pretreatment ultrasound and pelvic exam.
      CONCLUSIONS: In this study, medical abortion without screening ultrasound or
      pelvic exam resulted in no serious adverse events that were likely to have been
      prevented by those tests and was highly acceptable. IMPLICATIONS: Screening for
      medical abortion without exam or ultrasound shows promise as a means for
      increasing access to this service. More research is needed to develop screening
      criteria that are more inclusive and simpler for clinical use.

PMID- 29170089
TI  - Schistosomiasis in the first 1000 days.
AB  - Infections during the first 1000 days-the period from conception to a child's
      second birthday-can have lifelong effects on health, because this is a crucial
      phase of growth and development. There is increasing recognition of the burden
      and potential effects of schistosomiasis in women of reproductive age and young
      children. Exposure to schistosomes during pregnancy can modulate infant immune
      development and schistosomiasis can occur from early infancy, such that the high
      disease burden found in adolescents is often due to accumulation of infections
      with long-lived schistosomes from early life. Women of reproductive age and young
      children are largely neglected in mass drug administration programmes, but early
      treatment could avert subsequent disease. We evaluate the evidence that early
      schistosomiasis has adverse effects on birth, growth, and development. We also
      discuss the case for expanding public health interventions for schistosomiasis in
      women of reproductive age and preschool-age children, and the need for further
      research to evaluate the potential of treating women pre-conception to maximise
      health across the life course.

PMID- 29170090
TI  - Mucolipidosis type III gamma: Three novel mutation and genotype-phenotype study
      in eleven patients.
AB  - Mucolipidosis type III gamma (MLIII gamma) is a lysosomal storage disease
      characterized by joint stiffness, mild coarse face and corneal clouding, which
      becomes recognizable usually in childhood. Biallelic mutations in the GNPTG gene,
      which encode the gamma subunit of the N-acetylglucosamine-1-phosphotransferase
      enzyme, are the underlying cause of MLIII gamma. The aim of this study is to
      evaluate the longitudinal findings and genotype of eleven patients from eight
      families with MLIII gamma and to establish a genotype-phenotype correlation. The
      most frequently observed initial finding was stiffness of finger joints, which
      detected in patients between 18month-olds and five year-olds. However, in four
      patients presented here, initial finding was knee pain or waddling gait, which
      started between six-16years of age. All patients also had variable degrees of
      stiffness on large joints. The longest follow up period was 16years while the
      shortest was three years and six months. We observed that the patients who had an
      early onset disease and severe joint stiffness had also rapidly progressive joint
      involvement mostly localized in hands, shoulders, and hip. However; the patients
      with late onset and/or mild joint stiffness experienced slowly progressive
      symptoms. Most patients dropped in their growth curve in time and the ones who
      were severely affected reached the final height below the third centile. Seven
      disease-causing mutations, three of them novel, were detected in GNPTG gene.
      According to our clinical observations c.493_494insC and c.283_284insC mutations
      lead to a severe phenotype and c.196C>T, c.347_349del, c.652_655delTACT and
      c.445delG/c.367A>G mutations seemed to generate a milder phenotype.

PMID- 29170091
TI  - Potentiation of glutathione loss and nerve cell death by the transition metals
      iron and copper: Implications for age-related neurodegenerative diseases.
AB  - There is growing evidence for alterations in iron and copper homeostasis during
      aging that are exacerbated in neurodegenerative diseases such as Alzheimer's
      disease (AD). However, how iron and copper accumulation leads to nerve cell
      damage in AD is not clear. In order to better understand how iron and copper can
      contribute to nerve cell death, a simple, well-defined in vitro model of cell
      death, the oyxtosis assay, was used. This assay uses glutamate to induce
      glutathione (GSH) depletion which initiates a form of oxidative stress-induced
      programmed cell death. A reduction in GSH is seen in the aging brain, is
      associated with cognitive dysfunction and is accelerated in many CNS diseases
      including AD. It is shown that both iron and copper potentiate both GSH loss and
      cell death in this model. Iron and copper also potentiate cell death induced by
      other GSH depleters but not by compounds that induce oxidative stress via other
      pathways. At least part of the effects of copper on GSH are related to its
      ability to reduce the activity of glutamate cysteine ligase, the rate limiting
      enzyme in GSH synthesis. Both metals also alter several signaling pathways
      involved in modulating nerve cell death. Together, these results suggest that in
      vivo iron and copper may specifically enhance nerve cell death under conditions
      where GSH levels are reduced.

PMID- 29170093
TI  - A synthetic construct for genetic engineering of the emerging pathogenic yeast
      Candida auris.
AB  - Candida auris has recently emerged as a global cause of severe hospital-acquired
      fungal infections. To enable functional genomic approaches for this prominent
      pathogen, we designed a synthetic construct that can be used to genetically
      transform the genome-sequenced strain VPCI 479/P/13 of C. auris following an
      efficient electroporation procedure.

PMID- 29170094
TI  - The Choline Acetyltransferase (CHAT) Gene is Associated with Parahippocampal and
      Hippocampal Structure and Short-term Memory Span.
AB  - The CHAT gene encodes choline acetyltransferase, which is an enzyme responsible
      for the biosynthesis of the neurotransmitter acetylcholine in the brain. This
      study collected structural MRI, genetic, and behavioral data from 324 healthy
      Chinese adults, and examined the associations between CHAT genetic variants,
      parahippocampal and hippocampal structure, and short-term memory span. After
      controlling for intracranial volume, sex, and age, CHAT SNP rs12246528 had the
      strongest association with parahippocampal structure, with the A allele being
      linked to smaller volume, surface area, and thickness. SNP rs1917814 had the
      strongest association with hippocampal volume, with the T allele being linked to
      larger hippocampal volume. After controlling for sex and age, CHAT rs3729496 had
      the strongest association with memory span, with the T allele being associated
      with a greater memory span. Finally, the left parahippocampal gyrus surface area
      was positively associated with memory span. This study provides the first
      evidence for the involvement of the CHAT gene in parahippocampal and hippocampal
      structures and memory span in healthy Chinese adults.

PMID- 29170092
TI  - KRIT1 loss-of-function induces a chronic Nrf2-mediated adaptive homeostasis that
      sensitizes cells to oxidative stress: Implication for Cerebral Cavernous
      Malformation disease.
AB  - KRIT1 (CCM1) is a disease gene responsible for Cerebral Cavernous Malformations
      (CCM), a major cerebrovascular disease of proven genetic origin affecting 0.3
      0.5% of the population. Previously, we demonstrated that KRIT1 loss-of-function
      is associated with altered redox homeostasis and abnormal activation of the redox
      sensitive transcription factor c-Jun, which collectively result in pro-oxidative,
      pro-inflammatory and pro-angiogenic effects, suggesting a novel pathogenic
      mechanism for CCM disease and raising the possibility that KRIT1 loss-of-function
      exerts pleiotropic effects on multiple redox-sensitive mechanisms. To address
      this possibility, we investigated major redox-sensitive pathways and enzymatic
      systems that play critical roles in fundamental cytoprotective mechanisms of
      adaptive responses to oxidative stress, including the master Nrf2 antioxidant
      defense pathway and its downstream target Glyoxalase 1 (Glo1), a pivotal stress
      responsive defense enzyme involved in cellular protection against glycative and
      oxidative stress through the metabolism of methylglyoxal (MG). This is a potent
      post-translational protein modifier that may either contribute to increased
      oxidative molecular damage and cellular susceptibility to apoptosis, or enhance
      the activity of major apoptosis-protective proteins, including heat shock
      proteins (Hsps), promoting cell survival. Experimental outcomes showed that KRIT1
      loss-of-function induces a redox-sensitive sustained upregulation of Nrf2 and
      Glo1, and a drop in intracellular levels of MG-modified Hsp70 and Hsp27 proteins,
      leading to a chronic adaptive redox homeostasis that counteracts intrinsic
      oxidative stress but increases susceptibility to oxidative DNA damage and
      apoptosis, sensitizing cells to further oxidative challenges. While supporting
      and extending the pleiotropic functions of KRIT1, these findings shed new light
      on the mechanistic relationship between KRIT1 loss-of-function and enhanced cell
      predisposition to oxidative damage, thus providing valuable new insights into CCM
      pathogenesis and novel options for the development of preventive and therapeutic
      strategies.

PMID- 29170095
TI  - Assessing prevalence of and barriers to medication adherence in patients with
      uncontrolled diabetes attending primary healthcare clinics in Qatar.
AB  - BACKGROUND: Studies conducted in Qatar have reported a high prevalence of
      diabetic nephropathy, retinopathy, and neuropathy. These complications are often
      associated with poor medication adherence and uncontrolled diabetes. The
      objectives of this study were to determine the rate of medication adherence among
      patients with uncontrolled diabetes, and to compare the characteristics and
      identified barriers between patients with good and those with poor medication
      adherence. METHOD: A cross-sectional quantitative study was conducted among
      patients living in Qatar with uncontrolled diabetes attending primary healthcare
      clinics from October 2016 to January 2017. An interviewer-administered
      questionnaire comprising three sections was utilized in the study: patients'
      characteristics, Adherence to Refill and Medications Scale in Diabetes (ARMS-D),
      and barriers to medication adherence. ARMS-D is a validated tool that is used to
      identify adherence level among patients with diabetes. Descriptive and
      inferential statistics including regression analysis were used for data analysis.
      RESULTS: A total of 260 patients were included in the analysis. Overall, 73%
      (n=191) were nonadherent to their diabetes medications (ARMS-D score above 11).
      Nonadherent patients reported the majority of the pre-determined barriers to
      medication adherence with forgetfulness being the most commonly reported barrier.
      Multivariate linear regression analysis found age, ethnicity, education level,
      income level and HbA1c to be independent predictors of adherence. CONCLUSION: The
      findings of this study reaffirm the notion that non-adherence to medications
      among patients with uncontrolled diabetes within primary care setting is higher
      than the general diabetes population. This high prevalence is concerning and
      necessitates urgent interventions. Nonetheless, an in-depth understanding of
      barriers to medication adherence often requires qualitative research approach as
      these barriers are very complex and multifactorial in nature.

PMID- 29170096
TI  - Pb2+ modulates ryanodine receptors from the endoplasmic reticulum in rat brain.
AB  - Although the neurotoxic mechanism of lead (Pb2+) has been extensively studied, it
      is not well understood. The effects of Pb2+ on free cytosolic calcium (Ca2+)
      concentration and calcium-regulated events have been suggested to be major
      mechanisms in Pb2+ toxicity. Based on our previous findings that Pb2+ changes
      calcium release through ryanodine receptors (RyRs), the modulation of endoplasmic
      reticulum (ER) vesicular RyRs by Pb2+ was investigated further in the present
      study. The results of [3H]ryanodine binding assays showed that in the presence of
      a free Ca2+ concentration ([Ca2+]f) of 100MUM, Pb2+ modulated the equilibrium of
      [3H]ryanodine binding to brain RyRs, with a U-type dose-response curve, where
      minimal binding was observed at a free Pb2+ concentration ([Pb2+]f) of 0.39MUM.
      This modulation was also observed over a time course. Scatchard analysis
      indicated that both an increase in Kd and a possible decrease in Bmax were
      responsible for the decrease in binding induced by low [Pb2+]f. Moreover, the
      effects of Pb2+ on the function of ER RyRs in neurons might also be controlled by
      other RyR modulators. Whole-cell patch-clamp experiments revealed that dynamic
      calcium oscillations evoked by specific RyR agonists were depressed rapidly and
      reversibly by exposure to 10MUM Pb2+. Our study indicates that RyRs are molecular
      targets of Pb2+, and this interaction disturbs Ca2+ signals and leads to
      neurotoxicity.

PMID- 29170097
TI  - Mild cognitive impairment due to Alzheimer disease: Contemporary approaches to
      diagnostics and pharmacological intervention.
AB  - Alzheimer disease (AD) and related forms of dementia are among the main medical
      and social problems in the economically developed countries. It is connected with
      significant increase in human life span in these regions and with the absence of
      efficient medicines for treatment and prevention of such diseases. Lack of
      positive results in the developing of novel drugs for AD treatment stimulates
      special attention on problem of early diagnosis and drug discovery for
      pharmacotherapy on the very early stages of dementia, in particular, on mild
      cognitive impairments (MCI) due to AD. Here we review the state of art in the
      field of MCI diagnostics and analyze the data on the pharmacological agents
      developed for MCI treatment, which currently are in preclinical and clinical
      trials. The conclusion was made that only the agents that act on the very early
      pathogenetic stages of the disease, when the damage of cholinergic neurons is not
      observed, can be efficient for pharmacotherapeutic intervention of MCI.
      Therefore, the focused search and design of "disease-modifying" medicines should
      be accepted as the most (and may be the only) efficient strategy for treatment
      and prevention of MCI.

PMID- 29170099
TI  - Arrivals and "gifts" for Christmas Island.

PMID- 29170098
TI  - Serum Activity of Macrophage-Derived Adenosine Deaminase 2 Is Associated With
      Liver Fibrosis in Nonalcoholic Fatty Liver Disease.

PMID- 29170100
TI  - Genetic differentiation and phylogeny of 27 sheep populations based on structural
      gene loci.
AB  - To explore the genetic divergence and phylogeny of Chinese indigenous sheep
      breeds, in the current study, we analyzed the polymorphisms of 5 structural loci
      in ten sheep populations, including Sishui Fur, Sunite, Wurank, Bayinbuluke,
      Altay, Small-Tailed Han, Wadi, Tan, Tong and Hu sheep. The data were then
      compared with those from an additional 13 Asian and 4 European sheep populations
      acquired by the same experimental method. Based on the genetic distance and the
      results of a cluster analysis, we constructed the phylogenetic relationship of 27
      populations. The results showed that the sheep populations in this study could be
      classified into four genetic groups: "Mongolian", "Tibetan", "South-Southeast
      Asian" and "European" sheep groups. All 10 Chinese sheep breeds belonged to the
      "Mongolian sheep" lineage; however, Finnish Landrace sheep and Yunnan sheep could
      not be classified into any of the four groups. These results could provide a good
      reference for the protection and utilization of primary breed resources in China
      and phylogenic research on Asian sheep populations.

PMID- 29170101
TI  - A new approach of digital PCR system for non-invasive prenatal screening of
      trisomy 21.
AB  - BACKGROUND: Non-invasive prenatal screening (NIPS) of trisomy 21 (T21) using
      digital PCR (dPCR) with several advantages will be very effective. Here, we
      developed a dPCR system for T21 screening which allows high sensitivity and real
      time diagnosis and thus overcome sequence based analysis. METHODS: Cut-off value
      was established using DNA extracted from all 157 T21 negative samples including
      47 pregnant woman samples and 3 T21 positive pregnant woman samples extracted
      from 4 different sample types. To increase the portion of the cell-free fetal DNA
      (cffDNA) in maternal cell-free DNA (cfDNA), a size selection method was devised.
      We evaluated the clinical reliability of NIPS using dPCR through analysis of 877
      pregnant woman samples. RESULTS: We could demonstrate the possibility of NIPS
      using dPCR performed by applying cut-off value and size selection method. The
      overall accuracy was derived at 99.66% using 877 pregnant woman plasma samples.
      CONCLUSION: Our results showed that dPCR can meet the requirements for NIPS for
      T21. It is relatively inexpensive, easy to use in a screening method and
      compatible with ethical concerns regarding access to nucleotide sequence
      information. This study may be a basic data for the development of population
      wide screening for T21 in pregnant women.

PMID- 29170102
TI  - Pretreatment albumin to globulin ratio can serve as a prognostic marker in human
      cancers: a meta-analysis.
AB  - PURPOSE: Our meta-analysis aims to investigate the prognostic role of
      pretreatment albumin to globulin ratio (AGR) in human cancers. METHODS: Available
      databases were searched up to Sept 25th, 2017. Pooled hazard ratios (HRs) and
      risk ratio (RRs) with their corresponding 95% confidence intervals (CIs) were
      used to assess the prognostic impact of AGR on overall survival (OS)/disease-free
      survival (DFS)/progression-free survival (PFS) and 5-year mortality respectively.
      RESULTS: Totally, 28 studies with 15 356 cancer patients were included. Our
      results demonstrated that low pretreatment AGR is associated with poor OS
      (HR=2.08, 95%CI:1.78-2.44, univariate results; HR=1.75, 95%CI:1.56-1.97,
      multivariate results), poor DFS (HR=1.96, 95%CI:1.48-2.59, univariate results;
      HR=1.64, 95%CI:1.26-2.14, multivariate results) and poor PFS (HR=1.89, 95%CI:1.61
      2.22, univariate results; HR=1.66, 95%CI:1.32-2.0, multivariate results).
      Meanwhile, low pretreatment AGR is also associated with increased 5-year
      mortality (RR=2.12, 95%CI:1.48-3.03). Moreover, this significant correlation was
      not altered by stratified analysis according to publication times, sample sizes,
      patient origins, AGR cutoff values, cancer systems, treatment methods or HR
      sources. CONCLUSION: Low pretreatment AGR is associated with poor prognosis in
      human cancers, and AGR should be used as a prognostic marker during cancer
      therapy.

PMID- 29170103
TI  - Gamma-glutamyl transpeptidase-to-platelet ratio predicts the prognosis in HBV
      associated acute-on-chronic liver failure.
AB  - BACKGROUND: The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a new
      noninvasive marker for assessing liver fibrosis. We aimed to evaluate the
      performance of GPR for prediction of 90-day mortality in patients with acute-on
      chronic liver failure (ACLF). METHODS: A total of 355 patients with HBV
      associated ACLF were enrolled from two clinical centers and divided into training
      group (n=210) and validation group (n=145). Potential risk factors for 90-day
      mortality were analyzed. RESULTS: Age, MELD score and GPR were independent risk
      factors associated with ACLF prognosis. A new scoring system (MELD-GPR) was
      developed. MELD-GPR=9.211-0.029*age-0.290*MELD-0.460*GPR. For ACLF patients with
      liver cirrhosis, the area under the receiver operating characteristic curve
      (AUROC) of MELD-GPR was 0.788, which was significantly higher than that of MELD
      and MELD-Na (0.706 and 0.666, respectively). Patients were stratified into three
      groups according to MELD-GPR scores (high risk: <-0.19, intermediate risk: -0.19
      0.95, and low risk: >0.95), and the high-risk group (MELD-GPR<-0.19) had a poor
      prognosis (P<0.01). For ACLF patients without liver cirrhosis, MELD-GPR<0.95
      predicted a poor prognosis. CONCLUSIONS: Incorporating GPR into MELD may provide
      more accurate survival prediction in patients with HBV-ACLF.

PMID- 29170104
TI  - Unraveling unusual X-chromosome patterns during fragile-X syndrome genetic
      testing.
AB  - BACKGROUND: Fragile X syndrome (FXS) is the most common form of inherited
      intellectual disability (ID). Together with fragile X-associated tremor and
      ataxia (FXTAS) and fragile X-associated premature ovarian failure (POF)/primary
      ovarian insufficiency (POI), FXS depends on dysfunctional expression of the FMR1
      gene on Xq27.3. In most cases, FXS is caused by a >200 CGG repeats in FMR1 5'
      untranslated region (UTR) and by promoter hypermethylation that results in gene
      silencing. Males and females with unmethylated premutated alleles (repeats
      between 55 and 200) are at risk for FXTAS and POF/POI. METHODS: FXS molecular
      testing relied on PCR and methylation-specific Southern blot analysis of the FMR1
      5'UTR. Atypical Southern blot patterns were studied by X-chromosome
      microsatellite analysis, copy number dosage at DMD locus, amelogenin gender
      marker analysis and array-comparative genomic hybridization (array-CGH). RESULTS:
      Six men affected by ID and three women affected by ID and POF/POI underwent FXS
      molecular testing. They had normal FMR1 CGG repeats, but atypical X chromosome
      patterns. Further investigations revealed that the six males had Klinefelter
      syndrome (XXY), one female was a Turner mosaic (X0/XX) and two women had novel
      rearrangements involving X chromosome. CONCLUSIONS: Diagnostic investigation of
      atypical patterns at FMR1 locus can address patients and/or their relatives to
      further verify the condition by performing karyotyping and/or array-CGH.

PMID- 29170105
TI  - Heat shock protein 27 acts as a predictor of prognosis in chronic heart failure
      patients: Methodological issues.

PMID- 29170106
TI  - One-year in vitro stability of cardiac troponins and galectin-3 in different
      sample types.
AB  - BACKGROUND: We assessed the long-term in vitro stability of cardiac troponins and
      galectin-3 under different storage conditions. METHODS: We used high-sensitivity
      cardiac troponin I (hs-cTnI) and galectin-3 assays from Abbott and a high
      sensitivity cardiac troponin T (hs-cTnT) assay from Roche. The analyte
      concentrations of 30 patients were measured in heparin-treated plasma, EDTA
      treated plasma and serum samples after the following storage conditions: 1)
      samples used immediately after blood collection for baseline measurements; 2)
      samples stored for 0.5year at -80 degrees C after one freeze-thaw cycle; 3)
      samples stored for 1.0year at -80 degrees C after two freeze-thaw cycles; and 4)
      samples stored for 1.0year at -80 degrees C after one freeze-thaw cycle.
      According to the concept of acceptable change limits (ACL) the analytes were
      considered stable as long as the median concentration at a particular time point
      was >80%. RESULTS: Baseline hs-cTnI, hs-cTnT and galectin-3 concentrations ranged
      from 2.3 to 5436ng/L, from 5.3 to 850ng/L, and from 8.3 to 79.3ng/mL,
      respectively. After applying the default criterion for analyte stability, the
      three analytes were stable for at least 1.0year even after two freeze-thaw cycles
      for each sample type. We observed the following variation in analyte
      concentrations after storage relative to the baseline values: the interquartile
      range (IQR) of cardiac troponin results extended from approx. 80 to 115%, and the
      IQR of galectin-3 results extended from approx. 90 to 110%. CONCLUSION: hs-cTnI,
      hs-cTnT and galectin-3 were stable under the reported storage conditions
      irrespective of the sample type used. However, we observed a considerable
      variation in analyte concentrations after sample storage, which might affect the
      diagnostic/prognostic value of these analytes in individual patients using frozen
      blood samples.

PMID- 29170107
TI  - Analytical and clinical comparison of two fully automated immunoassay systems for
      the detection of autoantibodies to extractable nuclear antigens.
AB  - BACKGROUND: Detection of antinuclear antibodies (ANA) by indirect
      immunofluorescence assay (IIFA) is increasingly substituted by fully automated
      solid phase immunoassays. This study evaluated the performance of an automated
      chemiluminescence immunoassay (CIA) and fluorescence enzyme immunoassay (FEIA)
      and compared their performance to that of IIFA. METHODS: The study included an
      unselected prospective study population suspected of systemic autoimmune
      rheumatic disease. ANA were measured by IIFA, while in parallel sera were tested
      by CIA QUANTA Flash CTD Screen Plus on the BIO-FLASH(r) and FEIA EliA CTD Screen
      on the Phadia(r) 250 system. As validation, retrospective cohorts of patients
      with ANA-associated rheumatic disease (AARD) and healthy controls were tested.
      RESULTS: Prospectively, sensitivity of IIFA, CIA and FEIA was 90%, 99% and 92%,
      respectively. Specificity was 76%, 76% and 84%, respectively. Total percent
      agreements between the three methods were 75.2% (IIFA vs. CIA), 79.2% (IIFA vs.
      FEIA) and 85.4% (FEIA vs. CIA). The AUC values were 0.95 for CIA and 0.93 for
      FEIA and did not significantly differ. Retrospectively in individual AARD
      cohorts, similar results were obtained comparing both CTD screens. CONCLUSIONS:
      Both FEIA and CIA CTD screen significantly outperformed IIFA, with a higher
      specificity for FEIA and higher sensitivity for CIA. Based on ROC analysis, major
      contributor to the difference between the two solid phase immunoassays was the
      cut-off.

PMID- 29170108
TI  - A mathematical multiscale model of bone remodeling, accounting for pore space
      specific mechanosensation.
AB  - While bone tissue is a hierarchically organized material, mathematical
      formulations of bone remodeling are often defined on the level of a millimeter
      sized representative volume element (RVE), "smeared" over all types of bone
      microstructures seen at lower observation scales. Thus, there is no explicit
      consideration of the fact that the biological cells and biochemical factors
      driving bone remodeling are actually located in differently sized pore spaces:
      active osteoblasts and osteoclasts can be found in the vascular pores, whereas
      the lacunar pores host osteocytes - bone cells originating from former
      osteoblasts which were then "buried" in newly deposited extracellular bone
      matrix. We here propose a mathematical description which considers size and shape
      of the pore spaces where the biological and biochemical events take place. In
      particular, a previously published systems biology formulation, accounting for
      biochemical regulatory mechanisms such as the rank-rankl-opg pathway, is cast
      into a multiscale framework coupled to a poromicromechanical model. The latter
      gives access to the vascular and lacunar pore pressures arising from macroscopic
      loading. Extensive experimental data on the biological consequences of this
      loading strongly suggest that the aforementioned pore pressures, together with
      the loading frequency, are essential drivers of bone remodeling. The novel
      approach presented here allows for satisfactory simulation of the evolution of
      bone tissue under various loading conditions, and for different species;
      including scenarios such as mechanical dis- and overuse of murine and human bone,
      or in osteocyte-free bone.

PMID- 29170109
TI  - Activin A amplifies dysregulated BMP signaling and induces chondro-osseous
      differentiation of primary connective tissue progenitor cells in patients with
      fibrodysplasia ossificans progressiva (FOP).
AB  - BACKGROUND: Fibrodysplasia ossificans progressiva (FOP), is caused by mutations
      in the type I BMP receptor ACVR1 that lead to increased activation of the BMP
      pSmad1/5/8 signaling pathway. Recent findings suggest that Activin A (Act A)
      promiscuously stimulates the bone morphogenetic protein (BMP) signaling pathway
      in vitro and mediates heterotopic ossification (HO) in mouse models of FOP, but
      primary data from FOP patient cells are lacking. OBJECTIVE: To examine BMP
      pSmad1/5/8 pathway signaling and chondro-osseous differentiation in response to
      endogenous and exogenous Act A in primary connective tissue progenitor cells
      [CTPCs; also known as stem cells from human exfoliated deciduous teeth (SHED)
      cells] from patients with FOP. These cells express the common FOP mutation, ACVR1
      (R206H). RESULTS: We found that Act A amplifies dysregulated BMP pathway
      signaling in human FOP primary CTPCs cells through the Smad1/5/8 pathway and
      induces chondro-osseous differentiation. Amplification of BMP-pSmad1/5/8
      signaling was inhibited by Follistatin and by a neutralizing antibody to Activin
      A. The increased basal pSmad1/5/8 activity, as well as the hypoxia-induced
      stimulation of FOP CTPCs cells, were BMP4 and Act A independent. Importantly,
      either BMP4 or Act A stimulated pSmad1/5/8 pathway signaling but BMP4 signaling
      was not dependent on Activin A and vice versa. Circulating plasma levels of Act A
      or BMP4 are similar in controls compared to FOP patients, and suggest the
      potential for an autocrine or paracrine route for pathological signaling.
      CONCLUSIONS: The mutated FOP receptor [ACVR1 (R206H)] is hypersensitive to BMP4
      and uniquely sensitive (compared to the wild type receptor) to Act A. Both
      canonical and non-canonical ligands have a synergistic effect on BMP-pSmad1/5/8
      signaling in FOP CTPCs and may cooperate to alter the threshold for HO in FOP.
      Our findings in primary human FOP CTPCs have important implications for the
      design of clinical trials to inhibit dysregulated BMP pathway signaling in humans
      who have FOP.

PMID- 29170110
TI  - Association of anti-HER2 antibody with graphene oxide for curative treatment of
      osteosarcoma.
AB  - The finding of HER2 overexpression in osteosarcoma (OS) makes HER2 a potential
      therapeutic target. However, studies indicate OS cells are nonresponsive to anti
      HER2 antibody trastuzumab (TRA) therapy. We established stable, non-covalent
      association of TRA with nanomaterial graphene oxide (GO) to generated multivalent
      TRA/GO complexes that demonstrated markedly enhanced HER2-binding activity and
      capacity to rapidly kill OS cells. TRA/GO simultaneously induced oxidative stress
      and HER2 signaling in the target cells, leading to rapid depletion of the
      cellular inhibitors of apoptosis protein (cIAP) and caspase-8, formation of
      RIP1/RIPK3/MLKL necroptosome and necroptosis of the OS cells. Intravenous
      administration of TRA/GO eradicated established xenograft the OS in
      immunodeficient mice, resulting in indefinite survival of the animals, whereas
      TRA in its original form failed to do so. No appreciable side effects were
      observed with TRA/GO therapy. The results demonstrate a novel, nontoxic, curative
      therapy for a HER2pos cancer in a preclinical animal model.

PMID- 29170111
TI  - TAT-modified self-assembled cationic peptide nanoparticles as an efficient
      antibacterial agent.
AB  - The increasing emergence of drug resistant pathogenic bacteria poses a great
      challenge to clinical therapy and a threat to public health. Cationic peptides
      have received great attention for their unique antibacterial mechanism and
      ability to combat drug-resistant bacteria. In this study, we designed a TAT
      modified cationic peptide PA-28 which self-assembled into nanoparticles of about
      150 nm. These nanoparticles showed strong antimicrobial activities against both
      gram-positive and gram-negative bacteria, including drug-resistant bacteria. They
      were more potent than the unassembled counterpart peptide nonalysine (K9). Their
      antibacterial mechanism of directly destructing bacterial wall/membrane reduces
      the possibility of developing bacterial resistance. In vivo anti-infective
      experiments showed that these nanoparticles were able to penetrate the blood
      brain barrier to inhibit bacterial growth in infected brains of rats. In
      addition, these nanoparticles induced low hemolysis below the minimum inhibitory
      concentration. Therefore, the peptide designed in this study is a promising and
      efficient antibacterial agent against bacterial infections.

PMID- 29170112
TI  - Nanocellulose reinforced gellan-gum hydrogels as potential biological substitutes
      for annulus fibrosus tissue regeneration.
AB  - Intervertebral disc (IVD) degeneration is associated with both structural damage
      and aging related degeneration. Annulus fibrosus (AF) defects such as annular
      tears, herniation and discectomy require novel tissue engineering strategies to
      functionally repair AF tissue. An ideal construct will repair the AF by providing
      physical and biological support, facilitating regeneration. The presented
      strategy herein proposes a gellan gum-based construct reinforced with cellulose
      nanocrystals (nCell) as a biological self-gelling AF substitute. Nanocomposite
      hydrogels were fabricated and characterized with respect to hydrogel swelling
      capacity, degradation rate in vitro and mechanical properties. Rheological
      evaluation on the nanocomposites demonstrated the GGMA reinforcement with nCell
      promoted matrix entanglement with higher scaffold stiffness observed upon ionic
      crosslinking. Compressive mechanical tests demonstrated compressive modulus
      values close to those of the human AF tissue. Furthermore, cell culture studies
      with encapsulated bovine AF cells indicated that nanocomposite constructs
      promoted cell viability and a physiologically relevant cell morphology for up to
      fourteen days in vitro.

PMID- 29170113
TI  - Anti-Adherent Biomaterials for Prevention of Catheter Biofouling.
AB  - Medical device-associated infections present a leading global healthcare
      challenge, and effective strategies to prevent infections are urgently required.
      Herein, we present an innovative anti-adherent hydrogel copolymer as a candidate
      catheter coating with complementary hydrophobic drug-carrying and eluting
      capacities. The amphiphilic block copolymer, Poloxamer 188, was chemically
      derivatized with methacryloyl moieties and copolymerized with the hydrogel
      monomer, 2-hydroxyethyl methacrylate. Performance of the synthesized copolymers
      was evaluated in terms of equilibrium swelling, surface water wettability,
      mechanical integrity, resistance to encrustation and bacterial adherence, and
      ability to control release of the loaded fluoroquinolone antibiotic, ofloxacin.
      The developed matrices were able to provide significant protection from fouling,
      with observed reductions of over 90% in both adherence of the common urinary
      pathogen Escherichia coli and encrusting crystalline deposits of calcium and
      magnesium salts relative to the commonly employed hydrogel, poly (hydroxyethyl
      methacrylate). Additionally, the release kinetics of a loaded hydrophobic drug
      could be readily tuned through facile manipulation of polymer composition. This
      combinatorial approach shows significant promise in the development of suitable
      systems for prevention of catheter-associated infections.

PMID- 29170114
TI  - Protein-alginate complexes as pH-/ion-sensitive carriers of proteins.
AB  - Protein-alginate complexes were prepared with the objective of quantifying the
      influence of the parameters such as protein characteristics on the final complex
      properties and their dissociation rates. Cytochrome C, lysozyme, myoglobin,
      chymotrypsin, and bovine serum albumin were used as model proteins for preparing
      the complexes and physical properties such as composition, average diameter, and
      zeta potential of the complexes formed were measured. In addition, protein
      release kinetics from the complexes in response to changes in pH and ionic
      strength were investigated. The results clearly demonstrated that, even in the
      absence of a cation, proteins could be complexed with alginate and showed a
      decreased release rate under the appropriate conditions. Projection to Latent
      Structures was applied as a multivariate statistical analysis method to
      mathematically describe the final properties and the protein release kinetics as
      a function of the influencing variables. It was found that the physical
      characteristics of the complexes could be accurately modelled with low error
      thresholds indicative of good fit and prediction capabilities of the model. The
      statistical model indicated that the release kinetics parameters were highly
      dependent on the ionic strength and the protein net charge as a function of pH,
      demonstrating the potential use of these complexes in ion-/pH-sensitive delivery
      systems.

PMID- 29170115
TI  - Incorporation of surface-modified dry micronized poorly water-soluble drug
      powders into polymer strip films.
AB  - Recent work has established polymer strip films as a robust platform for delivery
      of poorly water-soluble drugs via slurry casting, in particular using stable drug
      nanosuspensions. Here, a simpler, robust method to directly incorporate dry
      micronized poorly water-soluble drug, fenofibrate (FNB), is introduced. As a
      major novelty, simultaneous surface modification using hydrophilic silica along
      with micronization was done using fluid energy mill (FEM) in order to reduce FNB
      hydrophobicity and powder agglomeration. It is hypothesized that silica coating
      promotes easy, uniform dispersion of micronized and coated FNB (MC-FNB) during
      direct mixing with aqueous hydroxypropyl methylcellulose (HPMC-E15LV) and
      glycerin solutions. Uniform dispersion leads to improved film critical quality
      attributes (CQAs) such as appearance, drug content uniformity and drug
      dissolution. The impact of polymer solution viscosity (low and high), mixer type
      (low versus high shear), and FNB surface modification on film CQAs were also
      assessed. Films with as-received FNB (AR-FNB) and micronized uncoated FNB (MU
      FNB) were prepared as control. When MC-FNB powders were used, films exhibited
      improved appearance (thickness uniformity, visible lumps/agglomerates), better
      drug content uniformity (expressed as relative standard deviation), fast and
      immediate drug release, and enhanced mechanical properties (tensile strength,
      elongation percentage), regardless of the polymer solution viscosity or mixer
      type. These results compare favorably with those reported using nanosuspensions
      of FNB, establishing the feasibility of directly incorporating surface modified
      micronized poorly water-soluble drug powders in film manufacturing.

PMID- 29170116
TI  - In vivo controlled release of fenretinide from long-acting release depots for
      chemoprevention of oral squamous cell carcinoma recurrence.
AB  - Local, long-acting release fenretinide (4HPR) millicylindrical implants were
      prepared and evaluated for their release kinetics in vivo and their ability to
      suppress oral cancer tumor explant growth. Poly(lactic-co-glycolic acid)(PLGA)
      implants were prepared as a function of drug loading and the presence of various
      excipients (pore-formers, solubilizers, crystallization inhibitors) to enhance
      release of the insoluble 4HPR. Release kinetics and bioerosion of PLGA were
      monitored both in vitro in a PBS/Tween 80 buffer and in vivo by recovery of the
      drug remaining at the injection site. 4HPR was released from PLGA implants much
      slower in vivo than in the drug solubilizing media in vitro, with a 3-week lag
      phase and continuous release of >2 months, but showed some release enhancement by
      addition of solubilizers. Water-soluble PVA/sucrose implants for release of 4HPR
      served to determine if drug dissolution provided suitable controlled release
      without the PLGA, and this formulation showed continuous drug release over 6
      weeks in vivo. Placement of PLGA-4HPR implants adjacent to oral cancer tumor
      murine xenografts showed inhibition of tumor growth relative to sham implants,
      indicating the potential for the local 4HPR delivery approach to be useful for
      oral cancer chemoprevention.

PMID- 29170117
TI  - Investigation of microemulsion and microemulsion gel formulations for dermal
      delivery of clotrimazole.
AB  - Dermal delivery of hydrophobic drugs by microemulsion (ME) formulations and
      effect from ME microstructures were studied. Anti-fungal drug, clotrimazole
      (CLOT), was used as the model compound. ME formulations possessing different
      microstructures were prepared using a ME system that contains isopropyl myristate
      as oil, Labrasol and Cremophor EL as surfactant and co-surfactant, and water.
      Permeation experiments on human cadaver skin were conducted for ME and the
      control formulations of different CLOT concentrations. Dermal delivery of CLOT
      assessed by the dermal tissue drug concentration was found to be significantly
      higher for MEs when compared with the control formulation, evidenced by dermal
      retention Enhancement Ratio (ERD) of 5.1, 2.8, and 3.0 for tested O/W, bi
      continuous, and W/O MEs, respectively. The highest concentration was observed
      with O/W ME, suggesting the ME microstructure is an important formulation
      variable for enhancing dermal delivery efficiency. ME gel formulations prepared
      by incorporating 1.0%(w/w) of Carbopol980 showed comparable dermal CLOT
      concentration to MEs, but up to 2.4 fold higher than the commercial CLOT cream
      product, Lotrimin(r). Furthermore, Fluorescein Isothiocynate (FITC), used as a
      model compound for highly hydrophobic drugs, was also studied for dermal delivery
      by MEs, and results show consistent ME microstructure effect, suggested by
      significantly higher FITC concentrations in all skin layers, SC, viable
      epidermis, and dermis, from O/W ME over bi-continuous and W/O MEs.

PMID- 29170118
TI  - Generic drug device combination products: Regulatory and scientific
      considerations.
AB  - Complex regulatory and scientific considerations exist for drug-device
      combination products submitted under an Abbreviated New Drug Application. The
      Agency has published several guidances to aid industry in the development of a
      generic drug-device combination product: providing recommendations on the types
      of studies necessary to establish bioequivalence, providing considerations on
      product quality and performance for certain types of device constituents, and
      most recently, providing tools to assess the proposed user interface when
      compared to the user interface of the Reference Listed Drug. In addition, the
      Office of Generic Drugs1 has established a regulatory science research program
      intended to support projects that examine scientific questions relating to the
      development of generic combination products and their associated regulatory
      review. Several research examples are described within this article, which
      demonstrate how equivalence can be evaluated when the function of the device
      could potentially impact drug delivery. Moreover, this article provides an
      overview of regulatory recommendations and ongoing scientific research efforts to
      further develop guidances and ultimately improve public access to generic
      combination products.

PMID- 29170119
TI  - Adult Patients with Pneumococcal Meningitis at a Neurosurgical Neurologic Center:
      Different Predisposing Conditions?
AB  - BACKGROUND: In previous studies of pneumococcal meningitis in adults within
      general hospitals or national cohorts, the most common predisposing conditions
      were otitis media, sinusitis, pneumonia, immunosuppression, alcoholism, and
      diabetes. The epidemiology of pneumococcal meningitis is changing because of the
      use of vaccines in childhood, and antibiotic resistance has increased. METHODS:
      We retrospectively reviewed the cases of patients with diagnoses of pneumococcal
      meningitis proved by an inflammatory cerebrospinal fluid (CSF) with a positive
      culture, treated during a period of 14 years at an adult neurosurgical neurologic
      referral center. Our aim was to define their clinical course, predisposing
      conditions, antimicrobial susceptibilities, and outcome. RESULTS: We reviewed the
      cases of 30 patients, 17 men and 13 women, with a mean age of 36.7 years.
      Fourteen patients (46.6%) had previous neurosurgery, 12 patients (40%) had CSF
      fistula, 8 had remote head trauma, and 8 also presented recurrent meningitis.
      Resistance to ceftriaxone or vancomycin was less than 5%, and penicillin
      resistance was 53%. Eight patients (26.7%) had died. An increased risk of death
      was associated with coma at admission, septic shock, upper gastrointestinal
      bleeding, mechanical ventilation, thrombocytopenia, and a low CSF opening
      pressure. CONCLUSIONS: We conclude that patients with pneumococcal meningitis
      treated at neurosurgical neurologic centers have different predisposing
      conditions with severe disease and high mortality, thus prompting us to recommend
      aggressive pneumococcal vaccination in patients with CSF leaks and severe head
      trauma. Prospective studies to identify which neurosurgical patients may benefit
      in the long term from a pneumococcal vaccine are urgently needed.

PMID- 29170120
TI  - Peripheral Blood Biomarkers Associated with Clinical Outcome in Non-Small Cell
      Lung Cancer Patients Treated with Nivolumab.
AB  - OBJECTIVE: The aim of this study was to identify baseline peripheral blood
      biomarkers associated with clinical outcome in patients with NSCLC treated with
      nivolumab. METHODS: Univariable and multivariable analyses were performed
      retrospectively for 134 patients with advanced or recurrent NSCLC treated with
      nivolumab to evaluate the relationship between survival and peripheral blood
      parameters measured before treatment initiation, including absolute neutrophil
      count (ANC), absolute lymphocyte count (ALC), absolute monocyte count, and
      absolute eosinophil count (AEC), as well as serum C-reactive protein and lactate
      dehydrogenase levels. Progression-free survival, overall survival, and response
      rate were determined. RESULTS: Among the variables selected by univariable
      analysis, a low ANC, high ALC, and high AEC were significantly and independently
      associated with both better progression-free survival (p = 0.001, p = 0.04, and p
      = 0.02, respectively) and better overall survival (p = 0.03, p = 0.03, and p =
      0.003, respectively) in multivariable analysis. Categorization of patients
      according to the number of favorable factors revealed that those with only one
      factor had a significantly worse outcome than those with two or three factors. A
      similar trend was apparent for patients with a programmed death 1 ligand tumor
      proportion score less than 50%, whereas all patients with a score of 50% or
      higher had at least two favorable factors. CONCLUSIONS: A baseline signature of a
      low ANC, high ALC, and high AEC was associated with a better outcome of nivolumab
      treatment, with the number of favorable factors identifying subgroups of patients
      differing in survival and response rate.

PMID- 29170121
TI  - Personal relative deprivation increases self-selected portion sizes and food
      intake.
AB  - Cues and experiences of the deprivation of financial/material resources have been
      associated with increased caloric intake and risk for overweight/obesity. Given
      that social comparisons may serve as a powerful reference for the adequacy of
      one's standing and resources, the present research tested whether subjective
      feelings of personal relative deprivation (PRD) or "losing out" to others
      stimulates calorie selection and intake. Study 1 demonstrated that self-reported
      chronic experiences of PRD positively predicted calories selected for a portion
      and consumed during an ad-libitum meal. Study 2 revealed that experimentally
      induced PRD resulted in an increase in the amount of calories selected on a
      portion selection task and a stronger desire to consume the foods. Consequently,
      these findings demonstrate that chronic and acute subjective deprivation of non
      food resources may contribute to socioeconomic gradients in obesity, and that
      perceived social inequality may have inherently obesogenic properties that
      promote excess calorie intake.

PMID- 29170122
TI  - Kudinoside-D, a triterpenoid saponin derived from Ilex kudingcha suppresses
      adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes.
AB  - The leaves of Ilex Kudingcha, locally named "Kudingcha" in China, has been
      traditionally applied for treating obesity. Studies have demonstrated that the
      ethanol extract of Ilex kudingcha have anti-adipogenic effects. However, the
      constituent which was responsible for its anti-obesity and its underlying
      molecular mechanism has not yet been elucidated. This research explored the anti
      obesity effect of kudinoside-D which was a main natural component of triterpenoid
      saponin from the ethanol extract of Ilex kudingcha, on lipid accumulation and the
      potential mechanism of action of adipogenesis in 3T3-L1 adipocytes. The
      adipocytes were treated with various concentrations of kudinoside D (0 to 40MUM)
      during differentiation. The image-based Oil Red O staining analyses revealed that
      KD-D, dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes
      with the IC50 is 59.49MUM. Meanwhile, major adipogenic transcription factor
      peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer
      binding protein-alpha (C/EBPalpha) and sterol regulatory element-binding protein
      1c (SREBP-1c) were significantly repressed as well as their target genes. The
      phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target
      phosphorylated-acetyl CoA carboxylase (ACC) expression were also increased. In
      addition, the inhibitory effects of KD-D on the expressions of PPARgamma and
      C/EBPalpha were weakened when cells were cotreated with AMPK inhibitor Compound
      C. These results indicated KD-D exerts anti-adipogenic effects through modulation
      of adipogenic transcription factors via AMPK signaling pathway. And the current
      findings demonstrated that KD-D was a potential therapeutic candidate for
      alleviating obesity and hyperlipidemia.

PMID- 29170123
TI  - Arundinosides A-G, new glucosyloxybenzyl 2R-benzylmalate derivatives from the
      aerial parts of Arundina graminifolia.
AB  - Seven new glucosyloxybenzyl 2R-benzylmalate derivatives, arundinosides A-G (1-7)
      were isolated from the aerial parts of the bamboo orchid Arundina graminifolia.
      This is the first occurrence of this class of compounds in the genus Arundina.
      Their planar structures and absolute configuration were determined by extensive
      NMR spectroscopic data as well as chemical conversion. Their neuroprotective
      properties were also evaluated on their potential ability to reduce the beta
      amyloid damage on PC12 cell model.

PMID- 29170124
TI  - Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via
      miR-200c/ABCB1 axis.
AB  - Long non-coding RNAs (lncRNAs) have been verified to participate in the
      tumorigenesis of multiple cancers. Nevertheless, the deepgoing role molecular
      mechanisms of lncRNAs on osteosarcoma chemoresistance remain unclear. In present
      study, we investigate the function of lncRNA LUCAT1 on osteosarcoma methotrexate
      (MTX) resistant phenotype and discover the potential regulatory mechanism.
      Results showed that LUCAT1 was up-regulated in MTX-resistant cells (MG63/MTX,
      HOS/MTX) compared to that in parental cells. LncRNA LUCAT1 and ABCB1 protein
      expression levels were both up-regulated when induced by different concentration
      of methotrexate. In vitro and vivo, LUCAT1 knockdown decreased the expression
      levels drug resistance related genes (MDR1, MRP5, LRP1), proliferation, invasion
      and tumor growth of osteosarcoma cells. Bioinformatics tools and luciferase assay
      reveled that miR-200c both targeted the 3'-UTR of LUCAT1 and ABCB1 mRNA,
      suggesting the modulation of LUCAT1 on ABCB1 through sponging miR-200c. Rescue
      experiments confirmed the combined role of LUCAT1, miR-200c and ABCB1 on
      osteosarcoma proliferation, invasion and methotrexate resistance. Overall,
      results indicate the vital role of LUCAT1 in the methotrexate resistance
      regulation through miR-200c/ABCB1 pathway, providing a novel insight and
      treatment strategy for osteosarcoma drug resistance.

PMID- 29170125
TI  - S-layer glycoprotein from Lactobacillus kefiri CIDCA 8348 enhances macrophages
      response to LPS in a Ca+2-dependent manner.
AB  - The S-layer is a (glyco)-proteinaceous envelope constituted by self-assembled
      subunits that form a two-dimensional lattice covering the surface of different
      species of Bacteria and Archaea. It could be considered as one of the most
      abundant biopolymers in our planet. Because of their unique self-assembly
      features, exhibiting repetitive identical physicochemical properties down to the
      subnanometer scale, as well as their involvement in specific interactions with
      host cells, the S-layer proteins (SLPs) show a high potential application in
      different areas of biotechnology, including the development of antigen carriers
      or new adjuvants. The presence of a glycosylated SLP on potentially probiotic
      Lactobacillus kefiri strains was previously described by our research group. In
      this study, we aim to investigate the role of carbohydrates present in the SLP
      from L. kefiri CIDCA 8348 (SLP-8348) in their internalization by murine
      macrophages, as well as to analyze their immunomodulatory capacity and their
      effect on LPS-stimulated macrophages. RAW 264.7 cells internalized the SLP-8348
      in a process that was mediated by carbohydrate-receptor interactions since it was
      inhibited by glucose, mannose or EGTA, a Ca+2 chelating agent. These results
      correlated with the recognition of SLP-8348 by ConA lectin. We further show that
      while SLP-8348 was not able to induce the activation of macrophages by itself, it
      favored the LPS-induced response, since there was a significant increase in the
      expression of surface cell markers MHC-II, CD86 and CD40, as well as in IL-6 and
      IL-10 expression at both transcript and protein levels, in comparison with LPS
      stimulated cells. The presence of EGTA completely abrogated this synergistic
      effect. Taken together, these results strongly suggest the involvement of both
      glycosidic residues and Ca+2 ions in the recognition of SLP-8348 by cellular
      receptors on murine macrophages. Moreover, these results suggest the potentiality
      of the SLP-8348 for the development of new adjuvants capable of stimulating
      antigen presenting cells by interaction with glycan receptors.

PMID- 29170126
TI  - Role of cAMP in phenotypic changes of osteoblasts.
AB  - Bone remodeling is precisely controlled by bone formation and bone resorption,
      and osteoblasts are responsible for both processes. Osteoblasts exhibit an
      osteoclastogenic phenotype in response to elevated intracellular cyclic AMP
      [cAMP]i levels. However, the role of cAMP in osteoblasts acquiring an osteogenic
      phenotype is controversial. To elucidate the effect of cAMP on both phenotypes,
      an osteoblast-like cell line, TMS-12, was established in our laboratory and used
      in this study. Dibutyryl-cAMP (dBcAMP), a cAMP analogue, inhibited mineralization
      in TMS-12 cells and MC3T3E1 cells (an osteoblast-like cell line) but promoted
      osteoclast-supporting activity in TMS-12 cells. Moreover, mineralization was
      inhibited in glucagon receptor-transduced TMS-12 cells (TMS-12GCGR) after
      glucagon treatment to increase endogenous [cAMP]i levels. However, the osteoclast
      supporting activity of TMS-12GCGR cells was stimulated by glucagon treatment.
      These cAMP-induced phenotypic changes of osteoblasts were also supported by their
      gene expression profile. These results suggest that [cAMP]i is an important
      factor mediating phenotypic changes of osteoblasts. Our findings may provide
      valuable insights into the mechanisms that underlie bone remodeling in both,
      healthy and diseased states.

PMID- 29170127
TI  - miR-455-3p serves as prognostic factor and regulates the proliferation and
      migration of non-small cell lung cancer through targeting HOXB5.
AB  - MicroRNAs (miRs) have been reported to play significantly roles in the initiation
      and progression of human cancers. miR-455-3p has been recently found could
      function as tumor suppressor in various human cancers. However, its expression
      and biological role in non-small cell lung cancer (NSCLC) remains elusive. In
      this study, we found miR-455-3p was markedly downregulated in NSCLC tissues and
      cell lines. Chi-square test to analyze the correlations between miR-455-3p
      expression and clinicopathological features revealed that miR-455-3p expression
      was correlated with poorly differentiated cancer and advanced tumor stage (P <
      0.05). Kaplan-Meier curve revealed that low expression of miR-455-3p was
      correlated with shorter 5-year survival time (P = 0.029). Univariate and
      multivariate analyses identified low miR-455-3p expression was an unfavorable
      prognostic factor for overall survival. Gain-of-function and loss-of-function
      studies revealed that miR-455-3p inhibits cell proliferation and migration in
      vitro. Computer algorithm and dual-luciferase reporter assay revealed that miR
      455-3p directly targets and suppresses HOXB5 in NSCLC. Further studies
      demonstrated that knockdown of HOXB5 attenuated the effect of miR-455-3p
      downregulation on cell proliferation and migration. Taken together, our results
      for the first time suggested that miR-455-3p was downregulated in NSCLC and was
      correlated with the poor prognosis of NSCLC patients. Also, miR-455-3p functions
      as tumor suppressor by directly targeting HOXB5 in NSCLC progression and may be
      used as a potential target for NSCLC treatment.

PMID- 29170128
TI  - Cerebrospinal fluid CD4+ T lymphocyte-derived miRNA-let-7b can enhances the
      diagnostic performance of Alzheimer's disease biomarkers.
AB  - Alzheimer's disease is very difficult to clinically diagnose. miRNAs constitute
      the promising next generation of Alzheimer's disease (AD) biomarkers and have the
      potential to diagnose neurodegenerative diseases. In this study, 94 subjects
      underwent extensive dementia screening. Let-7b miRNA was found to increase in
      association with the progression of AD, and the increase in let-7b miRNA was
      mainly due to CD4+ T cells in the cerebrospinal fluid (CSF). Additionally, let-7b
      was positively correlated with the expression of t-Tau and p-Tau. The inclusion
      of let-7b in Abeta40-Abeta42 or t-tau-p-tau logistic regression and receiver
      operating characteristic predictive models can significantly improve the
      diagnostic performance. Overall, let-7b has an important association with the
      pathology of AD and can be used as an adjunct to improve the diagnostic
      performance of traditional AD biomarkers.

PMID- 29170129
TI  - Rbfox family proteins make the homo- and hetero-oligomeric complexes.
AB  - Rbfox family of proteins that consists of Rbfox1, Rbfox2, and Rbfox3 in mammals
      regulates alternative pre-mRNA splicing in various tissues via direct binding to
      their RNA binding element. Although many studies have indicated the splicing
      activity of each member of the Rbfox family, the interactions of Rbfox family
      proteins are largely unknown. Here, we have investigated interactions among Rbfox
      family proteins. Co-immunoprecipitation (Co-IP) and GST-pull down assays
      confirmed that Rbfox proteins form homo and hetero complexes. Moreover, in vivo
      crosslinking using disuccinimidyl suberate treatment indicated that the Rbfox
      proteins form a dimer which then assembles with other proteins to form a large
      multiprotein complex. Duolink in situ proximity ligation (PLA) assay revealed
      that neuron specific Rbfox3 protein interacts with other Rbfox family proteins.
      This study is the first to provide an evidence that Rbfox family proteins form
      homo- and hetero-oligomeric complexes in vivo.

PMID- 29170130
TI  - MicroRNA-140 suppresses osteosarcoma tumor growth by enhancing anti-tumor immune
      response and blocking mTOR signaling.
AB  - Immune checkpoint blockade is proved to be a promising therapeutic strategy
      against several human malignancies. MicroRNAs (miRNAs) are ~22 nucleotide RNAs
      that play important roles in regulating gene expression, either suppressing its
      translation or speeding up its degradation. In this study, we demonstrated that
      miR-140 acts as a critical modulator of PD-L1 and is significantly reduced in
      osteosarcoma (OS). MiR-140 was inversely correlated with PD-L1 and luciferase
      reporter assay confirmed that miR-140 can direct regulate PD-L1 expression by
      binding to its 3'UTR. MiR-140 failed to influence tumor growth in nude mice,
      whereas markedly inhibited tumor growth in the immune-competent C57BL/6J mice.
      Mechanistically, the tumor-suppressive role of miR-140 was associated with the
      increased infiltrates of cytotoxic CD8+ T cells and the decreased infiltrates of
      myeloid-derived suppressive cells and regulatory T cells. Moreover, miR-140
      significantly inhibited mTOR signaling and combined miR-140 overexpression with
      pharmacological inhibition of mTOR signaling showed remarkable synergistic anti
      tumor effect. Collectively, our findings indicate that miR-140 exerts anti-OS
      efficacy by targeting immune checkpoint molecule PD-L1 and can be developed as a
      novel immunotherapeutic agent for the treatment of OS.

PMID- 29170132
TI  - High ALDH activity defines ovarian cancer stem-like cells with enhanced
      invasiveness and EMT progress which are responsible for tumor invasion.
AB  - Epithelial ovarian cancer (EOC) is highly metastatic and current therapeutics are
      unsatisfactory. Cancer stem/stem-like cells (CSCs/CSCLs) represent a rare
      population of undifferentiated oncogenic cells responsible for tumor initiation
      and maintenance. We identified ovarian cancer ALDHhigh (aldehyde dehydrogenase)
      population could perform not only strengthened CSCLs properties embodied in
      colony-formation, CSCs-markers expression, and tumorigenesis in vivo, but also a
      greater invasive capacity with advanced EMT progress and anti-apoptosis compared
      with ALDHlow cells. Furthermore, both the stemness and aggressive features, along
      with ALDHhigh percentages were in positive association with the invasiveness of
      cell lines for sorting, indicating the promotive role of ALDHhigh CSCLs in EOC
      neoplasia and metastasis, since the whole tumor was derived from the CSCLs with
      hyperactive self-renewal and aggression. Collectively, this study illustrates the
      interplay between ALDHhigh CSCLs and EOC invasion, and offers a novel application
      target for the EOC oncotherapy.

PMID- 29170131
TI  - Negative regulation of lncRNA GAS5 by miR-196a inhibits esophageal squamous cell
      carcinoma growth.
AB  - MiR-196a could play important roles in carcinogenesis by targeting many protein
      coding genes. However, little is known about whether miR-196a can target any long
      non-coding RNAs (lncRNAs). In the present study, we screen lncRNAs which are
      regulated by miRNA-196a in human esophageal squamous cell carcinoma (ESCC). We
      found that miR-196a could suppress the expression of lncRNA growth arrest
      specific 5(GAS5). GAS5 is frequently down-regulated in 86 paired human ESCC
      tissues. Importantly, there was lower GAS5 expression in the late stage of ESCC
      patients. The reduced expression of GAS5 in ESCC may not be related to DNA
      methylation but related to the high expression of miR-196a. In vitro and in vivo
      studies indicated that GAS5 could inhibit the growth of ESCC cells. Using
      Chromatin Isolation by RNA Purification-qPCR, we found that miR-196a could bind
      to GAS5. The Luciferase Reporter Assay indicated that miR-196a could bind to the
      seventh exon of GAS5. Additionally, both GAS5 and miR-196a could bind to Ago2
      which is a key component of the RNA-induced silencing complex (RISC). Together,
      these results suggest that GAS5 functions as a tumor suppressor gene in ESCC and
      is regulated by miR-196a involved in RISC.

PMID- 29170133
TI  - Downregulation of Bit1 expression promotes growth, anoikis resistance, and
      transformation of immortalized human bronchial epithelial cells via Erk
      activation-dependent suppression of E-cadherin.
AB  - The mitochondrial Bit1 protein exerts tumor-suppressive function in NSCLC through
      induction of anoikis and inhibition of EMT. Having this dual tumor suppressive
      effect, its downregulation in the established human lung adenocarcinoma A549 cell
      line resulted in potentiation of tumorigenicity and metastasis in vivo. However,
      the exact role of Bit1 in regulating malignant growth and transformation of human
      lung epithelial cells, which are origin of most forms of human lung cancers, has
      not been examined. To this end, we have downregulated the endogenous Bit1
      expression in the immortalized non-tumorigenic human bronchial epithelial BEAS-2B
      cells. Knockdown of Bit1 enhanced the growth and anoikis insensitivity of BEAS-2B
      cells. In line with their acquired anoikis resistance, the Bit1 knockdown BEAS-2B
      cells exhibited enhanced anchorage-independent growth in vitro but failed to form
      tumors in vivo. The loss of Bit1-induced transformed phenotypes was in part
      attributable to the repression of E-cadherin expression since forced exogenous E
      cadherin expression attenuated the malignant phenotypes of the Bit1 knockdown
      cells. Importantly, we show that the loss of Bit1 expression in BEAS-2B cells
      resulted in increased Erk activation, which functions upstream to promote TLE1
      mediated transcriptional repression of E-cadherin. These collective findings
      indicate that loss of Bit1 expression contributes to the acquisition of malignant
      phenotype of human lung epithelial cells via Erk activation-induced suppression
      of E-cadherin expression.

PMID- 29170135
TI  - Temporally coordinated spiking activity of human induced pluripotent stem cell
      derived neurons co-cultured with astrocytes.
AB  - In culture conditions, human induced-pluripotent stem cells (hiPSC)-derived
      neurons form synaptic connections with other cells and establish neuronal
      networks, which are expected to be an in vitro model system for drug discovery
      screening and toxicity testing. While early studies demonstrated effects of co
      culture of hiPSC-derived neurons with astroglial cells on survival and maturation
      of hiPSC-derived neurons, the population spiking patterns of such hiPSC-derived
      neurons have not been fully characterized. In this study, we analyzed temporal
      spiking patterns of hiPSC-derived neurons recorded by a multi-electrode array
      system. We discovered that specific sets of hiPSC-derived neurons co-cultured
      with astrocytes showed more frequent and highly coherent non-random synchronized
      spike trains and more dynamic changes in overall spike patterns over time. These
      temporally coordinated spiking patterns are physiological signs of organized
      circuits of hiPSC-derived neurons and suggest benefits of co-culture of hiPSC
      derived neurons with astrocytes.

PMID- 29170134
TI  - Synergistic chemo-photothermal therapy of tumor by hollow carbon nanospheres.
AB  - Combined use of different therapies is conducive to improve the effectiveness of
      cancer therapy. The chemo-photothermal therapy is commonly used in one
      nanocarrier to provide an excellent synergistic effect for cancer therapy over
      photothermal therapy (PTT) or chemotherapy alone. In this study, biocompatible
      and monodisperse hollow carbon nanospheres (HCNs) were developed as a
      multifunctional platform for the delivery of paclitaxel (PTX) and PTT of cancer
      simultaneously. The mesoporous HCNs have large pore volume and proper channels
      for loading and release of PTX. Upon near-infrared (NIR) laser illumination, the
      photothermal mediator of HCNs could effectively convert absorbed light into heat,
      which triggered rapid release of chemotherapeutic drug from HCNs through
      dissociating the interactions between PTX and HCNs by heat energy. A large number
      of tumor cells were significantly destroyed when hct116 cells treated with
      PTX@HCNs were irradiated, which was mainly attribute to the synergistic result of
      HCNs-mediated photothermal damage and cytotoxicity of light-triggered PTX
      release.

PMID- 29170136
TI  - Cereblon deficiency confers resistance against polymicrobial sepsis by the
      activation of AMP activated protein kinase and heme-oxygenase-1.
AB  - Cereblon (CRBN) has a pleiotropic role in important cellular processes and is a
      potential therapeutic target in several diseases, including mental retardation,
      cancer, and metabolic disorders. The role of CRBN in polymicrobial sepsis induced
      by cecal ligation and puncture (CLP) was investigated using CRBN-deficient (KO)
      mice. Survival following CLP was significantly higher in KO mice compared to wild
      type (WT) controls (50% vs 0% at day 6 after CLP). The improved survival of KO
      mice was accompanied by reduced peripheral blood bacterial load and lung injury.
      Serum tumor necrosis factor (TNF)-alpha and high mobility group box 1 (HMGB1)
      concentrations were significantly lower in KO mice than in WT mice. Peritoneal
      macrophages from KO mice with CLP-induced septic mouse had higher levels of
      activation of AMPK and heme oxygenase-1 (HO-1). Forced expression of CRBN in
      macrophage of KO mice suppressed activation of 5' adenosine monophosphate
      activated protein kinase (AMPK) and HO-1 and augmented expression of TNF-alpha
      and HMGB1 as inhibition of AMPK by compound C. These studies demonstrate the
      contribution of CRBN expression to the pathogenesis of CLP-induced sepsis and
      peritoneal macrophage responses and suggest a novel therapeutic modality for
      polymicrobial sepsis.

PMID- 29170137
TI  - One-size-fits-all dosing in oncology wastes money, innovation and lives.

PMID- 29170138
TI  - Pharmacokinetics of a sustained release formulation of PDGFbeta-receptor directed
      carrier proteins to target the fibrotic liver.

PMID- 29170139
TI  - Artful and multifaceted applications of carbon dot in biomedicine.
AB  - Carbon dots (C-dots) are luminescent carbon nanomaterial having good
      biocompatibility and low toxicity. The characteristic fluorescence emission
      property of C-dots establishes their role in optical imaging. C-dots which are
      superior to fluorescent dyes and semiconductor quantum dots act as a safer in
      vivo imaging probe. Apart from their bioimaging application, other applications
      in biomedicine such as drug delivery, cancer therapy, and gene delivery were
      studied. In this review, we present multifaceted applications of C-dots along
      with their synthesis, surface passivation, doping, and toxicity profile.

PMID- 29170140
TI  - A novel controlled release formulation of the Pin1 inhibitor ATRA to improve
      liver cancer therapy by simultaneously blocking multiple cancer pathways.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths
      worldwide largely due to lack of effective targeted drugs to simultaneously block
      multiple cancer-driving pathways. The identification of all-trans retinoic acid
      (ATRA) as a potent Pin1 inhibitor provides a promising candidate for HCC targeted
      therapy because Pin1 is overexpressed in most HCC and activates numerous cancer
      driving pathways. However, the efficacy of ATRA against solid tumors is limited
      due to its short half-life of 45min in humans. A slow-releasing ATRA formulation
      inhibits solid tumors such as HCC, but can be used only in animals. Here, we
      developed a one-step, cost-effective route to produce a novel biocompatible,
      biodegradable, and non-toxic controlled release formulation of ATRA for effective
      HCC therapy. We used supercritical carbon dioxide process to encapsulate ATRA in
      largely uniform poly L-lactic acid (PLLA) microparticles, with the efficiency of
      91.4% and yield of 68.3%, and ~4-fold higher Cmax and AUC over the slow-releasing
      ATRA formulation. ATRA-PLLA microparticles had good biocompatibility, and
      significantly enhanced the inhibitory potency of ATRA on HCC cell growth,
      improving IC50 by over 3-fold. ATRA-PLLA microparticles exerted its efficacy
      likely through degrading Pin1 and inhibiting multiple Pin1-regulated cancer
      pathways and cell cycle progression. Indeed, Pin1 knock-down abolished ATRA
      inhibitory effects on HCC cells and ATRA-PLLA did not inhibit normal liver cells,
      as expected because ATRA selectively inhibits active Pin1 in cancer cells.
      Moreover ATRA-PLLA microparticles significantly enhanced the efficacy of ATRA
      against HCC tumor growth in mice through reducing Pin1, with a better potency
      than the slow-releasing ATRA formulation, consistent with its improved
      pharmacokinetic profiles. This study illustrates an effective platform to produce
      controlled release formulation of anti-cancer drugs, and ATRA-PLLA microparticles
      might be a promising targeted drug for HCC therapy as PLLA is biocompatible,
      biodegradable and nontoxic to humans.

PMID- 29170141
TI  - RNA nanoparticle distribution and clearance in the eye after subconjunctival
      injection with and without thermosensitive hydrogels.
AB  - Thermodynamically and chemically stable RNA nanoparticles derived from the three
      way junction (3WJ) of the pRNA from bacteriophage phi29 DNA packaging motor were
      examined previously for ocular delivery. It was reported that, after
      subconjunctival injection, RNA nanoparticles with tri-way shape entered the
      corneal cells but not the retinal cells, whereas particle with four-way shape
      entered both corneal and retinal cells. The present study evaluated ocular
      delivery of RNA nanoparticles with various shapes and sizes, and assessed the
      effect of thermosensitive hydrogels (poly(lactic-co-glycolic acid)-b
      poly(ethylene glycol)-b-poly(lactic-co-glycolic acid); PLGA-PEG-PLGA) for
      increasing the retention of RNA nanoparticles in the eye. Fluorescence imaging of
      mouse eyes and fluorescence microscopy of dissected eye tissues from the
      conjunctiva, cornea, retina, and sclera were performed to determine the
      distribution and clearance of the nanoparticles in the eyes after subconjunctival
      injection in vivo. RNA nanoparticles entered the cells of the conjunctiva,
      cornea, retina, and sclera after subconjunctival delivery. The clearance of RNA
      pentagon was slower than both RNA square and triangle of the same designed edge
      length (10nm) in the eye, and the clearance of RNA squares of the longer edge
      lengths (10 and 20nm) was slower than RNA square of the shorter edge length
      (5nm), thus indicating that the size could affect ocular pharmacokinetics of the
      nanoparticles. At 24h after the injection, approximately 6-10% of the
      fluorescence signal from the larger nanoparticles in the study (RNA square of
      20nm edge length and RNA pentagon of 10nm edge length) remained in the eye, and
      up to 70% of the retinal cells contained the nanoparticles. The results suggest
      that the larger nanoparticles were "gulped" in conjunctival, corneal, retinal,
      and scleral cells, similar to the behavior observed in macrophages. Additionally,
      the combination of RNA nanoparticles with the thermosensitive polymers increased
      the retention of the nanoparticles in the eye.

PMID- 29170143
TI  - Cardiac magnetic resonance imaging in patients with a nonconditional cardiac
      implantable device: Good-quality images besides safety are essential.

PMID- 29170142
TI  - A robust microparticle platform for a STING-targeted adjuvant that enhances both
      humoral and cellular immunity during vaccination.
AB  - Most FDA-approved adjuvants for infectious agents boost humoral but not cellular
      immunity, and have poorly-understood mechanisms. Stimulator of interferon genes
      (STING, also known as MITA, MPYS, or ERIS) is an exciting adjuvant target due to
      its role in cyclic dinucleotide (CDN)-driven anti-viral immunity; however, a
      major hindrance is STING's cytosolic localization which requires intracellular
      delivery of its agonists. As a result, STING agonists administered in a soluble
      form have elicited suboptimal immune responses. Delivery of STING agonists via
      particle platforms has proven a more successful strategy, but the opportunity for
      improved formulations and bioactivity remains. In this study we evaluated the
      adjuvant activity of the potent STING agonist, CDN 3'3'-cGAMP (cGAMP),
      encapsulated in acid-sensitive acetalated dextran (Ace-DEX) polymeric
      microparticles (MPs) which passively target antigen-presenting cells for
      intracellular release. This formulation was superior to all particle delivery
      systems evaluated and maintained its bioactivity following a sterilizing dose of
      gamma irradiation. Compared to soluble cGAMP, the Ace-DEX cGAMP MPs enhanced type
      I interferon responses nearly 1000-fold in vitro and 50-fold in vivo, caused up
      to a 104-fold boost in antibody titers, increased Th1-associated responses, and
      expanded germinal center B cells and memory T cells. Furthermore, the
      encapsulated cGAMP elicited no observable toxicity in animals and achieved
      protective immunity against a lethal influenza challenge seven months post
      immunization when using CDN adjuvant doses up to 100-fold lower than previous
      reports. For these reasons, Ace-DEX MP-encapsulated cGAMP represents a potent
      vaccine adjuvant of humoral and cellular immunity.

PMID- 29170144
TI  - Coexistence of tachyarrhythmias in patients with tetralogy of Fallot.
AB  - BACKGROUND: The expanding population of adult patients with tetralogy of Fallot
      (ToF) requires knowledge of its long-term sequelae. OBJECTIVE: The purpose of
      this study was to examine the coexistence and order of appearance of atrial
      fibrillation (AF), other supraventricular tachycardias (SVTs), ventricular
      tachycardia (VT), and ventricular fibrillation (VF), and their impact on survival
      during long-term follow-up. METHODS: Adult, corrected ToF patients [N = 225; 128
      male; mean +/- SD (minimum-maximum) age 41 +/- 12 (19-79) years] were included in
      the study. Medical correspondence, ECGs, and Holter recordings were reviewed for
      documented AF, other SVTs, VT, and VF. RESULTS: During follow-up of 35 +/- 9 (16
      64) years, sustained tachyarrhythmias, including SVT (n=50, 22%), AF (n=29, 13%),
      VT (n=20, 9%), and VF (n=9, 4%), were observed in 71 patients (32%), of whom 27
      (38%) had coexistence of different tachyarrhythmias. In 18 patients with
      coexisting SVT and AF, SVT most often preceded AF in 13 (72%). Age at SVT onset
      was similar between those with and those without subsequent AF development (40 +/
      17 years vs 35 +/- 16 years; P = .283). However, age at SVT and AF onset were
      positively correlated (rho 0.585; P = .011). Prevalence of SVT/AF was associated
      with VT/VF prevalence (odds ratio [OR] 4.59; P < .001). Although 11% of patients
      with SVT/AF subsequently develop VT/VF, onset of SVT/AF could not predict future
      VT/VF development (OR 1.81; P = .233). Adult ToF patients are initially at risk
      for SVT development, followed by AF, VT, and VF at 46 (43-50), 56 (53-59), 57 (54
      61), and 62 (61-63) years after ToF correction (P < .001), respectively. Survival
      time decreased when sustained tachyarrhythmias developed (P = .024). Age at onset
      of SVT, AF, and VT was positively correlated with age at death (SVT: rho 0.734; P
      = .004; AF: rho 0.783; P = .007, VT: rho 0.755; P = .050). CONCLUSION:
      Coexistence of different (supra)ventricular tachyarrhythmias is frequently
      observed in adult ToF patients. In these patients, a specific order of these
      tachyarrhythmias was observed. Tachyarrhythmias are associated with decreased
      survival time, and, more importantly, age at tachyarrhythmia development
      positively correlates with age at death.

PMID- 29170145
TI  - Sharing Family Life Information Through Video Calls and Other Information and
      Communication Technologies and the Association With Family Well-Being: Population
      Based Survey.
AB  - BACKGROUND: The use of information and communication technologies (ICTs) for
      information sharing among family members is increasing dramatically. However,
      little is known about the associated factors and the influence on family well
      being. OBJECTIVE: The authors investigated the pattern and social determinants of
      family life information sharing with family and the associations of different
      methods of sharing with perceived family health, happiness, and harmony (3Hs) in
      Hong Kong, where mobile phone ownership and Internet access are among the most
      prevalent, easiest, and fastest in the world. METHODS: A territory-wide
      population-based telephone survey was conducted from January to August 2016 on
      different methods of family life information (ie, information related to family
      communication, relationships with family members, emotion and stress management)
      sharing with family members, including face-to-face, phone, instant messaging
      (IM), social media sites, video calls, and email. Family well-being was assessed
      by three single items on perceived family health, happiness, and harmony, with
      higher scores indicating better family well-being. Adjusted prevalence ratios
      were used to assess the associations of sociodemographic factors with family life
      information sharing, and adjusted beta coefficients for family well-being.
      RESULTS: Of 2017 respondents, face-to-face was the most common method to share
      family life information (74.45%, 1502/2017), followed by IM (40.86%, 824/2017),
      phone (28.10%, 567/2017), social media sites (11.91%, 240/2017), video calls
      (5.89%, 119/2017), and email (5.48%, 111/2017). Younger age and higher education
      were associated with the use of any (at least one) method, face-to-face, IM, and
      social media sites for sharing family life information (all P for trend <.01).
      Higher education was most strongly associated with the use of video calls
      (adjusted prevalence ratio=5.61, 95% CI 2.29-13.74). Higher household income was
      significantly associated with the use of any method, face-to-face, and IM (all P
      for trend <.05). Sharing family life information was associated with a higher
      level of perceived family well-being (beta=0.56, 95% CI 0.37-0.75), especially by
      face-to-face (beta=0.62, 95% CI 0.45-0.80) and video calls (beta=0.34, 95% CI
      0.04-0.65). The combination of face-to-face and video calls was most strongly
      associated with a higher level of perceived family well-being (beta=0.81, 95% CI
      0.45-1.16). CONCLUSIONS: The differential use of ICTs to share family life
      information was observed. The prevalence of video calls was low, but associated
      with much better family well-being. The results need to be confirmed by
      prospective and intervention studies to promote the use of video calls to
      communicate and share information with family, particularly in disadvantaged
      groups.

PMID- 29170146
TI  - An eHealth Intervention to Promote Physical Activity and Social Network of
      Single, Chronically Impaired Older Adults: Adaptation of an Existing Intervention
      Using Intervention Mapping.
AB  - BACKGROUND: Especially for single older adults with chronic diseases, physical
      inactivity and a poor social network are regarded as serious threats to their
      health and independence. The Active Plus intervention is an automated computer
      tailored eHealth intervention that has been proven effective to promote physical
      activity (PA) in the general population of adults older than 50 years. OBJECTIVE:
      The aim of this study was to report on the methods and results of the systematic
      adaptation of Active Plus to the wishes and needs of the subgroup of single
      people older than 65 years who have one or more chronic diseases, as this
      specific target population may encounter specific challenges regarding PA and
      social network. METHODS: The Intervention Mapping (IM) protocol was used to
      systematically adapt the existing intervention to optimally suit this specific
      target population. A literature study was performed, and quantitative as well as
      qualitative data were derived from health care professionals (by questionnaires,
      n=10) and the target population (by focus group interviews, n=14), which were
      then systematically integrated into the adapted intervention. RESULTS: As the
      health problems and the targeted behavior are largely the same in the original
      and adapted intervention, the outcome of the needs assessment was that the
      performance objectives remained the same. As found in the literature study and in
      data derived from health professionals and focus groups, the relative importance
      and operationalization of the relevant psychosocial determinants related to these
      objectives are different from the original intervention, resulting in a
      refinement of the change objectives to optimally fit the specific target
      population. This refinement also resulted in changes in the practical
      applications, program components, intervention materials, and the evaluation and
      implementation strategy for the subgroup of single, chronically impaired older
      adults. CONCLUSIONS: This study demonstrates that the adaptation of an existing
      intervention is an intensive process in which adopting the IM protocol is an
      invaluable tool. The study provides a broad insight in adapting interventions
      aimed at single older adults with a chronic disease. It is concluded that even
      when the new target population is a sizable segment of the original target
      population, the adapted intervention still needs considerable changes to
      optimally fit the needs and situational differences of the narrower target
      population.

PMID- 29170147
TI  - Bioimpedance Alerts from Cardiovascular Implantable Electronic Devices:
      Observational Study of Diagnostic Relevance and Clinical Outcomes.
AB  - BACKGROUND: The use of implantable cardioverter-defibrillators (ICDs) and cardiac
      resynchronization therapy (CRT) devices is expanding in the treatment of heart
      failure. Most of the current devices are equipped with remote monitoring
      functions, including bioimpedance for fluid status monitoring. The question
      remains whether bioimpedance measurements positively impact clinical outcome.
      OBJECTIVE: The aim of this study was to provide a comprehensive overview of the
      clinical interventions taken based on remote bioimpedance monitoring alerts and
      their impact on clinical outcome. METHODS: This is a single-center observational
      study of consecutive ICD and CRT patients (n=282) participating in protocol
      driven remote follow-up. Bioimpedance alerts were analyzed with subsequently
      triggered interventions. RESULTS: A total of 55.0% (155/282) of patients had an
      ICD or CRT device equipped with a remote bioimpedance algorithm. During 34 (SD
      12) months of follow-up, 1751 remote monitoring alarm notifications were received
      (2.2 per patient-year of follow-up), comprising 2096 unique alerts (2.6 per
      patient-year of follow-up). Since 591 (28.2%) of all incoming alerts were
      bioimpedance-related, patients with an ICD or CRT including a bioimpedance
      algorithm had significantly more alerts (3.4 versus 1.8 alerts per patient-year
      of follow-up, P<.001). Bioimpedance-only alerts resulted in a phone contact in
      91.0% (498/547) of cases, which triggered an actual intervention in 15.9%
      (87/547) of cases, since in 75.1% (411/547) of cases reenforcing heart failure
      education sufficed. Overall survival was lower in patients with a cardiovascular
      implantable electronic device with a bioimpedance algorithm; however, this
      difference was driven by differences in baseline characteristics (adjusted hazard
      ratio of 2.118, 95% CI 0.845-5.791). No significant differences between both
      groups were observed in terms of the number of follow-up visits in the outpatient
      heart failure clinic, the number of hospital admissions with a primary diagnosis
      of heart failure, or mean length of hospital stay. CONCLUSIONS: Bioimpedance-only
      alerts constituted a substantial amount of incoming alerts when turned on during
      remote follow-up and triggered an additional intervention in only 16% of cases
      since in 75% of cases, providing general heart failure education sufficed. The
      high frequency of heart failure education that was provided could have
      contributed to fewer heart failure-related hospitalizations despite significant
      differences in baseline characteristics.

PMID- 29170149
TI  - GP returners: then and now.

PMID- 29170148
TI  - A Group of 500 Women Whose Health May Depart Notably From the Norm: Protocol for
      a Cross-Sectional Survey.
AB  - BACKGROUND: Longitudinal studies of women's health often seek to identify
      predictors of good health. Research has shown that following simple guidelines
      can halve women's mortality. The ongoing Australian Longitudinal Study of Women's
      Health (ALSWH) shows that Australian women are getting better at reducing their
      smoking and alcohol use, and are generally diligent about attending recommended
      health screenings, but are becoming less successful at dealing with obesity.
      There are communities of women who live unusually healthy lives (Rosetans,
      Seventh-Day Adventists, traditional Japanese women), but their lifestyles are
      unlikely to be adopted widely. Universal Medicine (UM) is a complementary-to
      medicine approach that emphasizes personal empowerment and the importance of
      menstrual health symptoms. OBJECTIVE: This survey investigates whether the
      approximately 500 women associated with UM exhibit health status significantly
      above the norm. As part of this investigation, questions for a newly developed
      menstrual attitudes questionnaire will also be evaluated. METHODS: A quantitative
      cross-sectional survey of women in a UM cohort was designed with the help of
      three focus groups of women at three life stages: in menses, peri-menopausal, and
      menopausal. The menstrual attitudes portion of the survey incorporates the
      insights of these women regarding female health issues. The survey also includes
      41 questions taken from the ALSWH. Focus groups generated additional questions
      about symptoms experienced and attitudes toward female health issues. ALSWH
      questions, including a range of health scales like the Short Form 36 (SF-36),
      Center for Epidemiologic Studies Depression Scale, Perceived Control Scale,
      Kessler Psychological Distress Scale, and the Multi-Item Summed Score for
      Perceived Stress, along with questions about experienced major health events,
      were investigated and incorporated if considered suitable. RESULTS: The validity
      of the menstrual attitudes questionnaire will be evaluated with Cohen's kappa.
      ALSWH respondents and UM participants will be compared, using unweighted
      regression or regression weighted or normalized by age, education, and interest
      in alternative treatments (to increase comparability), as appropriate. Analyses
      will determine whether UM-related variables (being a UM participant, length of UM
      participation, number of UM events attended) are associated with: differences in
      the number of major health events and health symptoms experienced; SF-36 physical
      and mental health scores; body mass index; and consumption of alcohol, tobacco,
      sugar, salt, caffeine, and dairy. CONCLUSIONS: If women in the UM cohort are
      truly in substantially better health than the norm, further investigations may be
      worthwhile to see whether UM plays a causal role, and whether the women's
      practices are generalizable.

PMID- 29170150
TI  - Junior doctor who supplied benzodiazepines is suspended for 12 months.

PMID- 29170151
TI  - Social media and the intrauterine device: a YouTube content analysis.
AB  - BACKGROUND: YouTube's online archive of video testimonials related to health
      information are more commonly viewed than those developed by clinicians and
      professional groups, suggesting the importance of the patient experience to
      viewers. We specifically sought to examine the accuracy of information on, and
      projected acceptability of, the intrauterine device (IUD) from these YouTube
      testimonials. METHODS: We searched YouTube for videos about individual uploaders'
      IUD experiences, using the search terms 'intrauterine device', 'IUD', 'Mirena'
      and 'Paragard'. Given interest in user testimonials, we excluded professional and
      instructional videos belonging to commercial or non-profit entities. Two
      reviewers independently analysed the videos using a structured guide, with
      attention to inaccurate information. RESULTS: Of 86 identified videos, four
      videos featured clinicians and were excluded; 62 met inclusion criteria.
      Interrater agreement on IUD portrayal was good (K=0.73). Young (mean age 25,
      range 19-38, years), white (75%), nulliparous (61%) women primarily uploaded
      content. Most described placement of the LNG-IUS (65%), were posted within 1
      month of insertion (45%), and mentioned side effects (66%) - bleeding, pain, and
      partner sensation of the strings. About one-third of videos contained inaccurate
      information (34%) and were thought to project an overall negative experience
      (30%). Videos portraying IUDs negatively were associated with inaccurate
      information and/or mention of side effects. CONCLUSION: While one-third of IUD
      user testimonials on YouTube contained inaccurate information, the majority of
      IUD experiences were perceived by our study viewers to be positive.

PMID- 29170153
TI  - Doctor who grabbed nurse's breast is suspended for 12 months.

PMID- 29170152
TI  - Impact of Lipid Measurements in Youth in Addition to Conventional Clinic-Based
      Risk Factors on Predicting Preclinical Atherosclerosis in Adulthood:
      International Childhood Cardiovascular Cohort Consortium.
AB  - BACKGROUND: Data suggest that the prediction of adult cardiovascular disease
      using a model comprised entirely of adult nonlaboratory-based risk factors is
      equivalent to an approach that additionally incorporates adult lipid measures. We
      assessed and compared the utility of a risk model based solely on nonlaboratory
      risk factors in adolescence versus a lipid model based on nonlaboratory risk
      factors plus lipids for predicting high-risk carotid intima-media thickness
      (cIMT) in adulthood. METHODS: The study comprised 2893 participants 12 to 18
      years of age from 4 longitudinal cohort studies from the United States (Bogalusa
      Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult
      Health Study), and Finland (The Cardiovascular Risk in Young Finns Study) and
      followed into adulthood when cIMT was measured (mean follow-up, 23.4 years).
      Overweight status was defined according to the Cole classification. Hypertension
      was defined according to the Fourth Report on High Blood Pressure in Children and
      Adolescents from the National High Blood Pressure Education Program. High-risk
      plasma lipid levels were defined according to the National Cholesterol Education
      Program Expert Panel on Cholesterol Levels in Children. High cIMT was defined as
      a study-specific value >=90th percentile. Age and sex were included in each
      model. RESULTS: In univariate models, all risk factors except for borderline high
      and high triglycerides in adolescence were associated with high cIMT in
      adulthood. In multivariable models (relative risk [95% confidence interval]),
      male sex (2.7 [2.0-2.6]), prehypertension (1.4 [1.0-1.9]), hypertension (1.9 [1.3
      2.9]), overweight (2.0 [1.4-2.9]), obesity (3.7 [2.0-7.0]), borderline high low
      density lipoprotein cholesterol (1.6 [1.2-2.2]), high low-density lipoprotein
      cholesterol (1.6 [1.1-2.1]), and borderline low high-density lipoprotein
      cholesterol (1.4 [1.0-1.8]) remained significant predictors of high cIMT
      (P<0.05). The addition of lipids into the nonlaboratory risk model slightly but
      significantly improved discrimination in predicting high cIMT compared with
      nonlaboratory-based risk factors only (C statistics for laboratory-based model
      0.717 [95% confidence interval, 0.685-0.748] and for nonlaboratory 0.698 [95%
      confidence interval, 0.667-0.731]; P=0.02). CONCLUSIONS: Nonlaboratory-based risk
      factors and lipids measured in adolescence independently predicted preclinical
      atherosclerosis in young adulthood. The addition of lipid measurements to
      traditional clinic-based risk factor assessment provided a statistically
      significant but clinically modest improvement on adolescent prediction of high
      cIMT in adulthood.

PMID- 29170154
TI  - Are the risks of treatment to cure a child with severe sickle cell disease too
      high?

PMID- 29170155
TI  - Role created to bridge gap between trainees and senior managers is hailed a
      success.

PMID- 29170156
TI  - Mobile lung cancer testing in supermarket car parks is to be expanded.

PMID- 29170157
TI  - Ten essential papers for the practice of evidence-based medicine.
AB  - In this article we signpost readers to 10 papers we consider essential reading
      for anyone starting out on an evidence-based medicine journey. We have considered
      papers consisting a mix of old and new, seminal and cutting-edge that offer
      insight into what evidence-based medicine is, where it came from, why it matters
      and what it has achieved. This is balanced against some of the common criticisms
      of evidence-based medicine and efforts to tackle them. We have also highlighted
      papers acknowledging the importance of teaching and learning of the principles of
      evidence-based medicine and how health professionals can better use evidence in
      clinical decisions with patients.

PMID- 29170158
TI  - Early invasive strategy should be performed within 72 hours in high-risk patients
      with non-ST-elevation myocardial infarction.

PMID- 29170159
TI  - Reduced expression of cardiac ryanodine receptor protects against stress-induced
      ventricular tachyarrhythmia, but increases the susceptibility to cardiac
      alternans.
AB  - Reduced protein expression of the cardiac ryanodine receptor type 2 (RyR2) is
      thought to affect the susceptibility to stress-induced ventricular
      tachyarrhythmia (VT) and cardiac alternans, but direct evidence for the role of
      RyR2 protein expression in VT and cardiac alternans is lacking. Here, we used a
      mouse model (crrm1) that expresses a reduced level of the RyR2 protein to
      determine the impact of reduced RyR2 protein expression on the susceptibility to
      VT, cardiac alternans, cardiac hypertrophy, and sudden death.
      Electrocardiographic analysis revealed that after the injection of relatively
      high doses of caffeine and epinephrine (agents commonly used for stress test),
      wild-type (WT) mice displayed long-lasting VTs, whereas the crrm1 mutant mice
      exhibited no VTs at all, indicating that the crrm1 mutant mice are resistant to
      stress-induced VTs. Intact heart Ca2+ imaging and action potential (AP)
      recordings showed that the crrm1 mutant mice are more susceptible to fast-pacing
      induced Ca2+ alternans and AP duration alternans compared with WT mice. The crrm1
      mutant mice also showed an increased heart-to-body-weight ratio and incidence of
      sudden death at young ages. Furthermore, the crrm1 mutant hearts displayed
      altered Ca2+ transients with increased time-to-peak and decay time (T50),
      increased ventricular wall thickness and ventricular cell area compared with WT
      hearts. These results indicate that reduced RyR2 protein expression suppresses
      stress-induced VTs, but enhances the susceptibility to cardiac alternans,
      hypertrophy, and sudden death.

PMID- 29170160
TI  - Insulin selectively reduces mitochondrial uncoupling in brown adipose tissue in
      mice.
AB  - The purpose of the present study was to determine the effects of prolonged
      hyperinsulinemia on mitochondrial respiration and uncoupling in distinct adipose
      tissue depots. Sixteen-week-old male mice were injected daily with placebo or
      insulin to induce an artificial hyperinsulinemia for 28 days. Following the
      treatment period, mitochondrial respiration and degree of uncoupling were
      determined in permeabilized perirenal, inguinal, and interscapular adipose
      tissue. White adipose tissue (WAT) mitochondria (inguinal and perirenal) respire
      at substantially lower rates compared with brown adipose tissue (BAT). Insulin
      treatment resulted in a significant reduction in mitochondrial respiration in
      inguinal WAT (iWAT) and interscapular BAT (iBAT), but not in perirenal WAT
      (pWAT). Furthermore, these changes were accompanied by an insulin-induced
      reduction in UCP-1 (uncoupling protein 1) and PGC-1alpha in iWAT and iBAT only,
      but not in pWAT or skeletal muscle. Compared with adipose tissue mitochondria in
      placebo conditions, adipose tissue from hyperinsulinemic mice manifested a site
      specific reduction in mitochondrial respiration probably as a result of reduced
      uncoupling. These results may help explain weight gain so commonly seen with
      insulin treatment in type 2 diabetes mellitus.

PMID- 29170162
TI  - Classification of gastrointestinal stromal tumor syndromes.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract, thought to derive from neoplastic outgrowth of the
      interstitial cells of Cajal. Building on recent advances in recognition,
      classification and diagnosis, the past two decades have seen a changing paradigm
      with molecular diagnostics and targeted therapies. KIT and PDGFRA mutations
      account for 85-90% of GIST carcinogenesis. However, the remaining 10-15% of
      GISTs, which until recently were called KIT/PDGFRA wild-type GISTs, have been
      found to have one of the several mutations, including in the SDHA, B, C, D, BRAF
      and NF1 genes. Though most of such GISTs are sporadic, a number of families with
      high incidence rates of GISTs and other associated clinical manifestations have
      been reported and found to harbor germline mutations in KIT, PDGFRA, SDH subunits
      and NF1 The goal of this review is to describe the mutations, clinical
      manifestations and therapeutic implications of syndromic and inherited GISTs in
      light of recent studies of their clinicopathologic range and pathogenesis.

PMID- 29170161
TI  - CONSORT-Equity 2017 extension and elaboration for better reporting of health
      equity in randomised trials.

PMID- 29170163
TI  - MicroRNAs: tiny molecules with a significant role in mammalian follicular and
      oocyte development.
AB  - The genetic regulation of female fertility (follicular development, oocyte
      maturation and early preimplantation embryo development) involves the spatio
      temporal regulation of those genes that play key roles in various stages of the
      female reproductive axis. MicroRNAs (miRNAs), a class of small non-coding RNAs,
      are known to regulate the expression of a large proportion of such genes. In
      recent decades, multiple studies have aimed to determine the roles of these non
      coding RNAs in mammalian follicular development, oocyte growth and embryo
      development. These studies have applied a variety of approaches, including
      conditional knockout of miRNA biogenesis genes, high-throughput sequencing
      technologies for pattern recognition in miRNA expression and loss- and gain-of
      function of miRNAs in various animal models. In addition to the cellular miRNAs,
      a large variety of RNAs are found in circulation, being coupled with
      extracellular vesicles, proteins and lipids. Because of their potential as
      diagnostic markers for abnormal physiologies, there is increasing interest in the
      identification of extracellular miRNAs in various biological fluids and spent in
      vitro culture media. This review focuses on studies addressing the expression and
      potential role of cellular and extracellular miRNAs in mammalian follicular cell
      physiology and subsequent ovarian functionality and oocyte maturation.

PMID- 29170165
TI  - Philip Morris International introduces new heat-not-burn product, IQOS, in South
      Korea.

PMID- 29170166
TI  - E-cigarette brand mocks tobacco control warning labels.

PMID- 29170164
TI  - KIRREL is differentially expressed in adipose tissue from 'fertil+' and 'fertil-'
      cows: in vitro role in ovary?
AB  - We have previously shown that dairy cows carrying the 'fertil-' haplotype for one
      quantitative trait locus affecting female fertility located on the bovine
      chromosome three (QTL-F-Fert-BTA3) have a significantly lower conception rate and
      body weight after calving than cows carrying the 'fertil+' haplotype. Here, we
      compared by Tiling Array the expression of genes included in the QTL-F-Fert-BTA3
      in 'fertil+' and 'fertil-' adipose tissue one week after calving when plasma non
      esterified fatty acid concentrations were greater in 'fertil-' animals. We
      observed that thirty-one genes were overexpressed whereas twelve were under
      expressed in 'fertil+' as compared to 'fertil-' cows (P < 0.05). By quantitative
      PCR and immunoblot we confirmed that adipose tissue KIRREL mRNA and protein were
      significantly greater expressed in 'fertil+' than in 'fertil-'. KIRREL mRNA is
      abundant in bovine kidney, adipose tissue, pituitary, and ovary and detectable in
      hypothalamus and mammary gland. Its expression (mRNA and protein) is greater in
      kidney of 'fertil+' than 'fertil-' cows (P < 0.05). KIRREL (mRNA and protein) is
      also present in the different ovarian cells with a greater expression in
      granulosa cells of 'fertil+' than 'fertil-' cows. In cultured granulosa cells,
      recombinant KIRREL halved steroid secretion in basal state (P < 0.05). It also
      decreased cell proliferation (P < 0.05) and in vitro oocyte maturation (P <
      0.05). These results were associated to a rapid increase in MAPK1/3 and MAPK14
      phosphorylation in granulosa cells and to a decrease in MAPK1/3 phosphorylation
      in oocyte. Thus, KIRREL could be a potential metabolic messenger linking body
      composition and fertility.

PMID- 29170168
TI  - Revealing the complexity of quitting smoking: a qualitative grounded theory study
      of the natural history of quitting in Australian ex-smokers.
AB  - OBJECTIVE: To explore the quitting histories of Australian ex-smokers in order to
      develop an understanding of the varied contribution of smoking cessation
      assistance (either pharmacotherapy or professionally mediated behavioural
      support) to the process of quitting. DESIGN: Qualitative grounded theory study;
      in-depth interviews. PARTICIPANTS: 37 Australian adult ex-smokers (24-68 years;
      15 men, 22 women) who quit in the past 6-24 months. RESULTS: Although
      participants' individual quitting histories and their overall experiences of
      quitting were unique, when the 37 quitting histories were compared it was clear
      two experiences were common to almost all participants: almost no one quit at
      their first quit attempt and almost everyone started out quitting unassisted.
      Furthermore, distinct patterns existed in the timing and use of assistance, in
      particular the age at which assistance was first used, how some participants were
      resolutely uninterested in assistance, and how assistance might have contributed
      to the process of successful quitting even if not used on the final quit attempt.
      Importantly, three patterns in use of assistance were identified: (1) only ever
      tried to quit unassisted (n=13); (2) started unassisted, tried assistance but
      reverted back to unassisted (n=13); (3) started unassisted, tried assistance and
      quit with assistance (n=11). For most participants, insight into what quitting
      would require was only gained through prior quitting experiences with and without
      assistance. For a number of participants, interest in assistance was at its
      lowest when the participant was most ready to quit. CONCLUSION: Quitting should
      be viewed as a process drawing on elements of assisted and unassisted quitting
      rather than a stand-alone event that can be labelled as strictly assisted or
      unassisted.

PMID- 29170167
TI  - Neighbourhood characteristics and health outcomes: evaluating the association
      between socioeconomic status, tobacco store density and health outcomes in
      Baltimore City.
AB  - INTRODUCTION: Several studies suggest that the health of an individual is
      influenced by the socioeconomic status (SES) of the community in which he or she
      lives. This analysis seeks to understand the relationship between SES, tobacco
      store density and health outcomes at the neighbourhood level in a large urban
      community. METHODS: Data from the 55 neighbourhoods of Baltimore City were
      reviewed and parametric tests compared demographics and health outcomes for low
      income and high-income neighbourhoods, defined by the 50th percentile in median
      household income. Summary statistics are expressed as median. Tobacco store
      density was evaluated as both an outcome and a predictor. Association between
      tobacco store densities and health outcomes was determined using Moran's I and
      spatial regression analyses to account for autocorrelation. RESULTS: Compared
      with higher-income neighbourhoods, lower-income neighbourhoods had higher tobacco
      store densities (30.5 vs 16.5 stores per 10 000 persons, P=0.01), lower life
      expectancy (68.5 vs 74.9 years, P<0.001) and higher age-adjusted mortality (130.8
      vs 102.1 deaths per 10 000 persons, P<0.001), even when controlling for other
      store densities, median household income, race, education status and age of
      residents. CONCLUSION: In Baltimore City, median household income is inversely
      associated with tobacco store density, indicating poorer neighbourhoods in
      Baltimore City have greater accessibility to tobacco. Additionally, tobacco store
      density was linked to lower life expectancy, which underscores the necessity for
      interventions to reduce tobacco store densities.

PMID- 29170169
TI  - Thoracic aortic transection resulting in a type B dissection following blunt
      trauma.
AB  - A 39-year-old man sustained an acute grade III aortic injury resulting in a type
      B aortic dissection in the setting of severe traumatic brain injury, cervical
      spine injury and multiple orthopaedic injuries following a motorcycle crash. The
      patient underwent an emergent thoracic endovascular aortic repair, complicated by
      a thoracic pseudoaneurysm rupture and ongoing exsanguination from a persistent
      type 1 endoleak. Additional stent grafts were required to gain control of the
      endoleak. The patient ultimately progressed to brain death post procedure in the
      intensive care unit. This case reviews treatment considerations in the context of
      a blunt thoracic aortic transection and distal dissection with concomitant
      polytrauma.

PMID- 29170170
TI  - Twist on a classic: vitamin D and hypercalcaemia of malignancy.
AB  - Malignancy is the most common cause of hypercalcaemia in the inpatient setting.
      Most cases are caused by tumour production of parathyroid hormone-related protein
      and osseous metastases. In less than 1% of cases, hypercalcaemia is driven by
      increased production of 1,25-dihydroxyvitamin D (1,25(OH)2D), a mechanism most
      commonly seen in haematological malignancies. Here, we describe a woman with
      metastatic small cell cervical carcinoma who developed hypercalcaemia secondary
      to paraneoplastic overproduction of 1,25(OH)2D, a finding that, to our knowledge,
      has not been previously associated with this cancer. We also review the current
      cases of solid tumours reported to have this mechanism of hypercalcaemia and the
      evidence behind multiple therapeutic approaches.

PMID- 29170171
TI  - Dental implants in a patient with suspected leucocyte adhesion deficiency.
AB  - Aggressive periodontitis and premature tooth loss in leucocyte adhesion
      deficiency (LAD) have adverse functional and psychological consequences on
      affected individuals. Dental implant rehabilitation might become necessary to
      overcome the functional and psychological adverse effects of LAD periodontitis,
      especially in patients with milder forms who are expected to have a relatively
      normal life expectancy. Outcome of dental implants in patients with LAD has not
      been previously reported; we describe the dental rehabilitation of a 24-year-old
      man with clinical features of LAD using endosseous dental implants.

PMID- 29170172
TI  - Eosinophilic myocarditis as a first presentation of eosinophilic granulomatosis
      with polyangiitis (Churg-Strauss syndrome).
AB  - We present the case of a 28-year-old man who presented with chest pain and
      elevated cardiac biomarkers, with no evidence of acute ischaemia. He had a
      pronounced eosinophilia, abnormal echocardiographic, cardiac MRI and CT findings.
      He underwent transbronchial biopsy of carinal lymph nodes and of lung parenchyma.
      Endomyocardial biopsy yielded an eosinophilic infiltrate. He was treated with
      high dose glucocorticoids and made a rapid recovery. Testing for FIP1L1-PDGFRA
      and other BCR-ABL1 mutations was negative. Ultimately, he was diagnosed with
      eosinophilic granulomatosis with polyangiitis, also known as Churg-Strauss
      syndrome.

PMID- 29170173
TI  - Kikuchi-Fujimoto disease: an unusual presentation of meningitis in a returning
      traveller.
AB  - A 19-year-old, previously healthy woman developed a pruritic erythematous
      maculopapular rash on her bilateral palms and wrists, right-sided tender cervical
      lymphadenopathy and nightly fevers and headaches 5 days after returning from a 1
      month trip to Cambodia. She presented 2 weeks after her trip due to ongoing
      nightly fevers to a maximum of 38.8 degrees C. She was given empiric doxycycline
      for possible rickettsial disease, though an extensive infectious workup returned
      without positive findings. Lumbar puncture was performed on hospital day 4, and
      spinal fluid analysis was consistent with aseptic meningitis. On hospital day 5,
      core biopsy and fine-needle aspiration were performed on the largest anterior
      cervical lymph node. Her fever curve gradually improved, and she was discharged
      on hospital day 6. Results of the lymph node biopsy were finalized 5 days after
      discharge and were compatible with Kikuchi's lymphadenitis. Symptoms had
      completely resolved on follow-up with infectious disease and rheumatology.

PMID- 29170174
TI  - Wernicke's encephalopathy secondary to gestational hyperthyroidism.

PMID- 29170175
TI  - Schizophrenia and anaesthesia.
AB  - Administering anaesthesia for elderly patients with chronic schizophrenia has
      always been a great challenge to anaesthetists. These patients will usually be on
      multiple antipsychotic drugs for many years and may lead to delayed awakening,
      cardiovascular instability, arrhythmias and sudden cardiac death during general
      anaesthesia. This case report is about the perioperative anaesthetic management
      of an elderly schizophrenic patient undergoing removal of femur implant. This
      article will explore important drug interactions and available options for a
      successful anaesthesia.

PMID- 29170176
TI  - Rare presentation of cementoblastoma associated with the deciduous maxillary
      second molar.
AB  - Cementoblastoma is a benign odontogenic neoplasm accounting for less than 0.69%
      8% of all odontogenic tumours and is characterised by the presence of sheets of
      cementum-like tissue demonstrating large number of reversal lines. It shows an
      unlimited growth potential and a recurrence rate as high as 37.1%. It most
      commonly affects the permanent mandibular molars. This paper presents the third
      reported case of cementoblastoma affecting the deciduous maxillary posterior
      dentition. A 12-year-old male patient reported to the Department of Oral and
      Maxillofacial Pathology with a chief complaint of pain and swelling in relation
      to the deciduous maxillary left second molar.

PMID- 29170177
TI  - A regressing spindle cell tumour of Reed.

PMID- 29170178
TI  - False-positive phencyclidine (PCP) on urine drug screen attributed to
      desvenlafaxine (Pristiq) use.
AB  - We report a likely false-positive phencyclidine (PCP) result detected with a
      urine drug screen (UDS) (Medtox, St Paul, Minnesota, USA) in the setting of
      therapeutic desvenlafaxine (Pristiq) use. Desvenlafaxine (O-desmethylvenlafaxine)
      is the active metabolite of venlafaxine (Effexor). Prior reports have confirmed
      venlafaxine use resulting in a false-positive for PCP on a UDS. However, there
      has been a paucity of reporting of commercially available desvenlafaxine
      formulations (Pristiq, Khedezla) resulting in false-positives for PCP on a UDS.

PMID- 29170179
TI  - ANCA-positive IgA nephropathy without necrotising or crescentic
      glomerulonephritis: a clinical conundrum.
AB  - IgA nephropathy, the most prevalent form of primary glomerular disease, usually
      portends a favourable outcome. Antineutrophil cytoplasmic autoantibodies (ANCAs)
      have been reported in association with IgA nephropathy in a small subset of
      patients, mostly presenting with rapidly progressive glomerulonephritis and
      necrotising crescentic lesions. Herein, we describe a case of IgA nephropathy,
      positive serum cytoplasmic and perinuclear ANCAs with anti-myeloperoxidase
      antibody, and preserved renal function without any histological evidence of
      necrotising or crescentic glomerulonephritis. Based on available mechanistic and
      clinical data, we opine that such patients could benefit from close monitoring of
      renal function.

PMID- 29170180
TI  - Muscle fasciculation detected by ECG.
AB  - A 79-year-old man presented to hospital with scald burns to the perineum after a
      syncopal episode while in a hot bathtub. Admission ECG was misdiagnosed as
      possible ventricular fibrillation with high-frequency irregular waveforms in lead
      V2 at a rate exceeding 1000 cycles per minute, corresponding to intervening
      skeletal muscle contractions unrelated to the heart. Follow-up ECG showed full
      resolution of the irregular waveforms. Muscle fasciculations are a benign cause
      of ECG artefact and can easily be mistaken for serious cardiac arrhythmias. While
      most muscle fasciculations detected on ECG are benign, in the correct clinical
      circumstance these waveforms indicate an underlying neuromuscular disorder. The
      patient underwent surgical skin grafting with no perioperative cardiac
      complications and no further syncope in hospital.

PMID- 29170181
TI  - Multiple hybrid sutures of bucket handle injury on the lateral and medial
      meniscus of the knee.
AB  - The objective of the study is to show possibilities of several combinations of
      suture techniques in a rare bicompartmental bucket handle injury. According to
      specific injury characteristics, combined suturing techniques were used. The
      option for different meniscal suture techniques in the two knee compartments
      allowed the patient, after completing the treatment, to return to his activities
      with a preserved meniscus. Although meniscectomy continues to be a chosen
      technique in bucket handle injury, we attempted to show a case of bicompartmental
      meniscal suture with different techniques. In this, which could be a case of
      rapid resolution and quick return to activities with bicompartmental
      meniscectomy, we chose to preserve the menisci with more complex techniques and
      longer rehabilitation, believing that the preservation of this structure could be
      extremely valuable in the long term.

PMID- 29170182
TI  - Panuveitis simulating ocular Behcet's in cases of chronic myelogenous leukaemia
      in remission.
AB  - We report two patients with chronic myelogenous leukaemia (CML) in remission
      phase who developed panuveitis simulating Behcet's disease. A 26-year-old man
      presented with bilateral panuveitis (hypopyon in the right eye, bilateral
      anterior segment inflammation, vitritis and retinitis). He was on imatinib for
      CML which was in remission. He gave a history of recurrent oral ulcers. The
      panuveitis responded to oral and topical steroids but recurred after the steroids
      were stopped. His ocular condition again stabilised on restarting oral steroids
      and azathioprine. The second patient, a 28-year-old man, presented with bilateral
      anterior segment inflammation, vitritis, exudative retinal detachment and
      hypopyon in the right eye. He was also on imatinib with the CML being in
      remission. The uveitis and exudative retinal detachment improved on systemic and
      topical steroids. The vision of this patient did not improve as optic atrophy
      ensued. The panuveitis seen in our patients with CML responded favourably to oral
      steroids/immunosuppressant therapy.

PMID- 29170183
TI  - Unilateral erythaema nodosum: atypical presentation in paediatrics.

PMID- 29170184
TI  - Large, extra-abdominal leiomyoma of the round ligament with carneous
      degeneration.
AB  - Round ligament tumours represent a rare entity that can present similarly to an
      incarcerated hernia. Basic understanding and appropriate preoperative management
      is imperative in order to differentiate between the two diagnoses. Leiomyoma is
      the most common type of round ligament tumour. It is associated with oestrogen
      exposure and is more common in the presence of uterine leiomyomas. Here we
      discuss a 68-year-old woman who presented with a palpable left inguinal mass that
      progressively grew in size, associated with pelvic pressure and discomfort. On
      surgical resection, the mass was found to be derived from the round ligament at
      the entrance of the external inguinal ring. Pathology confirmed a round ligament
      leiomyoma, measuring 25*9*8.5 cm. This case is the largest round ligament
      leiomyoma recorded to date and the first to exhibit carneous degeneration. A
      review of the current literature is also provided.

PMID- 29170185
TI  - Dysosmia and dysgeusia associated with duloxetine.
AB  - Common adverse effects of serotonin-norepinephrine reuptake inhibitors are
      nausea, dry mouth, dizziness and headache. We describe the case of a patient with
      dysosmia and subsequent dysgeusia associated with duloxetine. A 68-year-old
      Japanese woman with a history of type 1 diabetes mellitus, hypertension, insomnia
      and reflux esophagitis presented to a local hospital with bilateral leg pain; she
      was treated with duloxetine. However, after 4 weeks, she sensed rotten egg smell,
      experienced nausea and vomiting and was admitted to our hospital. We diagnosed
      dysosmia using the T&T olfactometer threshold test and dysgeusia using filter
      paper disk method. Taste was assessed using electrogustometry. We suspected that
      dysosmia and dysgeusia were adverse effects of duloxetine. After stopping
      duloxetine, her symptoms gradually subsided and the above test results improved,
      despite continuing the other ongoing medication. To the best of our knowledge,
      this is the first case report of dysosmia and dysgeusia associated with
      duloxetine.

PMID- 29170186
TI  - A case of large right MCA stroke with hyperdense MCA sign in CT imaging.

PMID- 29170187
TI  - The rare occurrence of cutaneous and mucosal lichen planus in HIV infection.

PMID- 29170188
TI  - Tenon patch graft for corneal fistula: a rare entity treated by a simple
      technique.
AB  - A 50-year-old patient presented with dull aching pain with some discomfort in his
      right eye for the past 2 weeks. History revealed the patient had a past episode
      of infective keratitis managed medically in a local hospital. The last follow-up
      record suggested a diagnosis of healed keratitis with corneoiridic scar. On
      examination, the patient had visual acuity of hand movement and a corneoiridic
      scar of 7*7 mm with an inferotemporal translucent cystic area measuring 3*4 mm in
      size with underlying uveal tissue visible. Seidel test was found to be positive
      confirming leakage. For this, a tenon patch over the area of defect along with
      anterior chamber formation was done. On postoperative day 1, the graft was well
      attached and anterior chamber was formed with no leak on Seidel test. Intraocular
      pressure was 16 mm Hg.

PMID- 29170189
TI  - Characteristic imaging findings in pulmonary fat embolism syndrome (FES).

PMID- 29170190
TI  - Myoclonus as a late manifestation of West Nile disease.

PMID- 29170191
TI  - Chronic GVHD: progress in salvage treatment?

PMID- 29170192
TI  - CAR emissions: cytokines tell the story.

PMID- 29170193
TI  - Road trip to remission with CARs.

PMID- 29170194
TI  - Low VWF: an established mild bleeding disorder?

PMID- 29170195
TI  - Carcinocythemia (carcinoma cell leukemia).

PMID- 29170196
TI  - "Soccer ball" cells to "donut" cells: an unusual case of Richter syndrome.

PMID- 29170197
TI  - 'The more we change, the more we remain the same': female feticide continues
      unabated in India.
AB  - In North India, preference for sons has been blamed for repeated incidents of
      female feticide, despite the legislation in the form of the Pre-Conception and
      Pre-Natal Diagnostic Techniques Act, 2002. We describe how a team of local
      private doctors offer package deals to pregnant women and their families in rural
      areas. The fetal sex is determined at night using a portable ultrasonography
      machine.If the fetus is a girl, an immediate induced abortion is offered in the
      clients' home. If complications arise, women are advised to attend hospital. Such
      a patient visited us with a history of bleeding per vagina following incomplete
      induced abortion. This case study highlights the fact that female feticide
      continues to occur in India.

PMID- 29170198
TI  - Going above and beneath the call of duty: the luck egalitarian claims of
      healthcare heroes, and the accomodation of professionally-motivated treatment
      refusal.

PMID- 29170199
TI  - Ethics briefing.

PMID- 29170200
TI  - Response to: 'Acquiring new N-glycosylation sites in variable regions of
      immunoglobulin genes by somatic hypermutation is a common feature of autoimmune
      diseases' by Visser et al.

PMID- 29170201
TI  - 2017 EULAR/ACR classification criteria for adult and juvenile idiopathic
      inflammatory myopathies and their major subgroups: little emphasis on
      autoantibodies, why?

PMID- 29170202
TI  - Work disability in gout: a population-based case-control study.
AB  - OBJECTIVES: To examine the extent and cost of work disability among patients with
      gout compared with matched population controls and to analyse predictors of work
      disability. METHODS: A regional cohort study using data from Swedish national and
      regional registries from January 2000 through December 2012, including 4571
      patients with gout of working age, with a first recorded diagnosis of gout in the
      years 2003-2009 and 22 482 population controls, matched by age, sex and place of
      residence. Differences in baseline characteristics (educational level, income,
      previous employment and comorbidities) and the number of work-loss days
      (absenteeism) due to sick leave and disability pension for 3 years after
      identification were calculated. Predictors for new-onset work absenteeism (>90
      days/year) in a subset were determined by conditional logistic regression.
      RESULTS: Patients with gout (median age 53 years) had significantly more
      comorbidities, lower income and lower level of education than matched controls.
      The average work absentee rate during the 3-year follow-up period was higher
      among patients with gout than controls, 22% and 14%, respectively (P<0.0001). New
      onset absenteeism was in multivariate analyses significantly predicted by gout
      (OR 1.47; 95% CI 1.23 to 1.75). Other variables independently related to new
      onset absenteeism were education <=12 years, previous unemployment and history of
      sick leave, in addition to several comorbidities (renal disease, cardiovascular
      disease, alcohol abuse and obesity). CONCLUSIONS: Gout is associated with
      substantially higher work absenteeism and costs for society due to productivity
      loss, after adjusting for associated comorbidities and socioeconomic differences.
      Whether more intensive treatment of gout is cost-effective needs to be addressed
      in future studies.

PMID- 29170204
TI  - Comment on "Water harvesting from air with metal-organic frameworks powered by
      natural sunlight".
AB  - Kim et al (Reports, 28 April 2017, p. 430) describe a method for harvesting water
      from air, using a metal-organic framework (MOF) as the adsorbent. The process as
      described in the paper is, however, inadequate, and the system cannot deliver the
      claimed amount of liquid water in an arid climate. A modification of the process
      design and the use of more suitable MOFs may be more likely to achieve the goals
      targeted by Kim et al.

PMID- 29170205
TI  - Response to Comment on "Water harvesting from air with metal-organic frameworks
      powered by natural sunlight".
AB  - The Comment by Meunier states that the process we described in our report cannot
      deliver the claimed amount of liquid water in an arid climate. This statement is
      not valid because the parameters presented in our study were inappropriately
      combined to draw misguided conclusions.

PMID- 29170207
TI  - Blurring disciplinary boundaries.

PMID- 29170203
TI  - Identification of a novel locus on chromosome 2q13, which predisposes to clinical
      vertebral fractures independently of bone density.
AB  - OBJECTIVES: To identify genetic determinants of susceptibility to clinical
      vertebral fractures, which is an important complication of osteoporosis. METHODS:
      Here we conduct a genome-wide association study in 1553 postmenopausal women with
      clinical vertebral fractures and 4340 controls, with a two-stage replication
      involving 1028 cases and 3762 controls. Potentially causal variants were
      identified using expression quantitative trait loci (eQTL) data from transiliac
      bone biopsies and bioinformatic studies. RESULTS: A locus tagged by rs10190845
      was identified on chromosome 2q13, which was significantly associated with
      clinical vertebral fracture (P=1.04*10-9) with a large effect size (OR 1.74, 95%
      CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several
      potentially functional SNPs that are associated with expression of the positional
      candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family
      20 member 1). Three other suggestive loci were identified on chromosomes 1p31,
      11q12 and 15q11. All these loci were novel and had not previously been associated
      with bone mineral density or clinical fractures. CONCLUSION: We have identified a
      novel genetic variant that is associated with clinical vertebral fractures by
      mechanisms that are independent of BMD. Further studies are now in progress to
      validate this association and evaluate the underlying mechanism.

PMID- 29170206
TI  - Structural insights into ion conduction by channelrhodopsin 2.
AB  - The light-gated ion channel channelrhodopsin 2 (ChR2) from Chlamydomonas
      reinhardtii is a major optogenetic tool. Photon absorption starts a well
      characterized photocycle, but the structural basis for the regulation of channel
      opening remains unclear. We present high-resolution structures of ChR2 and the
      C128T mutant, which has a markedly increased open-state lifetime. The structure
      reveals two cavities on the intracellular side and two cavities on the
      extracellular side. They are connected by extended hydrogen-bonding networks
      involving water molecules and side-chain residues. Central is the retinal Schiff
      base that controls and synchronizes three gates that separate the cavities.
      Separate from this network is the DC gate that comprises a water-mediated bond
      between C128 and D156 and interacts directly with the retinal Schiff base.
      Comparison with the C128T structure reveals a direct connection of the DC gate to
      the central gate and suggests how the gating mechanism is affected by subtle
      tuning of the Schiff base's interactions.

PMID- 29170209
TI  - Battle over drilling in Arctic refuge reignites.

PMID- 29170210
TI  - GM banana shows promise against deadly fungus strain.

PMID- 29170211
TI  - Congress offers defense scientists a bigger payday.

PMID- 29170212
TI  - An earthly search for gold's cosmic origins.

PMID- 29170213
TI  - Do bacteriophage guests protect human health?

PMID- 29170214
TI  - Survey of archaea in the body reveals other microbial guests.

PMID- 29170215
TI  - Tougher than hell.

PMID- 29170216
TI  - Into the hot zone.

PMID- 29170217
TI  - Why do Earth's equatorial waves head east?

PMID- 29170218
TI  - Editing peptide presentation to T cells.

PMID- 29170219
TI  - Viruses hijack a host lncRNA to replicate.

PMID- 29170220
TI  - As the extension, so the twist.

PMID- 29170221
TI  - Enhancing the RNA engineering toolkit.

PMID- 29170222
TI  - The way forward for vector control.

PMID- 29170224
TI  - Quantum interference beyond the fringe.

PMID- 29170223
TI  - Channelrhodopsin reveals its dark secrets.

PMID- 29170225
TI  - Valuing water for sustainable development.

PMID- 29170226
TI  - Mexico's logging threatens butterflies.

PMID- 29170227
TI  - China's new era of ecological civilization.

PMID- 29170229
TI  - Ecuador's sharks face threats from within.

PMID- 29170232
TI  - Ten-month-old infants infer the value of goals from the costs of actions.
AB  - Infants understand that people pursue goals, but how do they learn which goals
      people prefer? We tested whether infants solve this problem by inverting a mental
      model of action planning, trading off the costs of acting against the rewards
      actions bring. After seeing an agent attain two goals equally often at varying
      costs, infants expected the agent to prefer the goal it attained through costlier
      actions. These expectations held across three experiments that conveyed cost
      through different physical path features (height, width, and incline angle),
      suggesting that an abstract variable-such as "force," "work," or "effort"
      supported infants' inferences. We modeled infants' expectations as Bayesian
      inferences over utility-theoretic calculations, providing a bridge to recent
      quantitative accounts of action understanding in older children and adults.

PMID- 29170231
TI  - Structure-property relationships from universal signatures of plasticity in
      disordered solids.
AB  - When deformed beyond their elastic limits, crystalline solids flow plastically
      via particle rearrangements localized around structural defects. Disordered
      solids also flow, but without obvious structural defects. We link structure to
      plasticity in disordered solids via a microscopic structural quantity,
      "softness," designed by machine learning to be maximally predictive of
      rearrangements. Experimental results and computations enabled us to measure the
      spatial correlations and strain response of softness, as well as two measures of
      plasticity: the size of rearrangements and the yield strain. All four quantities
      maintained remarkable commonality in their values for disordered packings of
      objects ranging from atoms to grains, spanning seven orders of magnitude in
      diameter and 13 orders of magnitude in elastic modulus. These commonalities link
      the spatial correlations and strain response of softness to rearrangement size
      and yield strain, respectively.

PMID- 29170233
TI  - The fundamental advantages of temporal networks.
AB  - Most networked systems of scientific interest are characterized by temporal
      links, meaning the network's structure changes over time. Link temporality has
      been shown to hinder many dynamical processes, from information spreading to
      accessibility, by disrupting network paths. Considering the ubiquity of temporal
      networks in nature, we ask: Are there any advantages of the networks'
      temporality? We use an analytical framework to show that temporal networks can,
      compared to their static counterparts, reach controllability faster, demand
      orders of magnitude less control energy, and have control trajectories, that are
      considerably more compact than those characterizing static networks. Thus,
      temporality ensures a degree of flexibility that would be unattainable in static
      networks, enhancing our ability to control them.

PMID- 29170230
TI  - Molecular and cellular reorganization of neural circuits in the human lineage.
AB  - To better understand the molecular and cellular differences in brain organization
      between human and nonhuman primates, we performed transcriptome sequencing of 16
      regions of adult human, chimpanzee, and macaque brains. Integration with human
      single-cell transcriptomic data revealed global, regional, and cell-type-specific
      species expression differences in genes representing distinct functional
      categories. We validated and further characterized the human specificity of genes
      enriched in distinct cell types through histological and functional analyses,
      including rare subpallial-derived interneurons expressing dopamine biosynthesis
      genes enriched in the human striatum and absent in the nonhuman African ape
      neocortex. Our integrated analysis of the generated data revealed diverse
      molecular and cellular features of the phylogenetic reorganization of the human
      brain across multiple levels, with relevance for brain function and disease.

PMID- 29170234
TI  - Major role of nitrite-oxidizing bacteria in dark ocean carbon fixation.
AB  - Carbon fixation by chemoautotrophic microorganisms in the dark ocean has a major
      impact on global carbon cycling and ecological relationships in the ocean's
      interior, but the relevant taxa and energy sources remain enigmatic. We show
      evidence that nitrite-oxidizing bacteria affiliated with the Nitrospinae phylum
      are important in dark ocean chemoautotrophy. Single-cell genomics and community
      metagenomics revealed that Nitrospinae are the most abundant and globally
      distributed nitrite-oxidizing bacteria in the ocean. Metaproteomics and
      metatranscriptomics analyses suggest that nitrite oxidation is the main pathway
      of energy production in Nitrospinae. Microautoradiography, linked with catalyzed
      reporter deposition fluorescence in situ hybridization, indicated that
      Nitrospinae fix 15 to 45% of inorganic carbon in the mesopelagic western North
      Atlantic. Nitrite oxidation may have a greater impact on the carbon cycle than
      previously assumed.

PMID- 29170236
TI  - Three-dimensional mechanical metamaterials with a twist.
AB  - Rationally designed artificial materials enable mechanical properties that are
      inaccessible with ordinary materials. Pushing on an ordinary linearly elastic bar
      can cause it to be deformed in many ways. However, a twist, the counterpart of
      optical activity in the static case, is strictly zero. The unavailability of this
      degree of freedom hinders applications in terms of mode conversion and the
      realization of advanced mechanical designs using coordinate transformations.
      Here, we aim at realizing microstructured three-dimensional elastic chiral
      mechanical metamaterials that overcome this limitation. On overall millimeter
      sized samples, we measure twists per axial strain exceeding 2 degrees /%. Scaling
      up the number of unit cells for fixed sample dimensions, the twist is robust due
      to metamaterial stiffening, indicating a characteristic length scale and bringing
      the aforementioned applications into reach.

PMID- 29170235
TI  - Control of zeolite framework flexibility and pore topology for separation of
      ethane and ethylene.
AB  - The discovery of new materials for separating ethylene from ethane by adsorption,
      instead of using cryogenic distillation, is a key milestone for molecular
      separations because of the multiple and widely extended uses of these molecules
      in industry. This technique has the potential to provide tremendous energy
      savings when compared with the currently used cryogenic distillation process for
      ethylene produced through steam cracking. Here we describe the synthesis and
      structural determination of a flexible pure silica zeolite (ITQ-55). This
      material can kinetically separate ethylene from ethane with an unprecedented
      selectivity of ~100, owing to its distinctive pore topology with large heart
      shaped cages and framework flexibility. Control of such properties extends the
      boundaries for applicability of zeolites to challenging separations.

PMID- 29170237
TI  - Creation of a Bose-condensed gas of 87Rb by laser cooling.
AB  - Protocols for attaining quantum degeneracy in atomic gases almost exclusively
      rely on evaporative cooling, a time-consuming final step associated with
      substantial atom loss. We demonstrate direct laser cooling of a gas of rubidium
      87 (87Rb) atoms to quantum degeneracy. The method is fast and induces little atom
      loss. The atoms are trapped in a two-dimensional optical lattice that enables
      cycles of compression to increase the density, followed by Raman sideband cooling
      to decrease the temperature. From a starting number of 2000 atoms, 1400 atoms
      reach quantum degeneracy in 300 milliseconds, as confirmed by a bimodal velocity
      distribution. The method should be broadly applicable to many bosonic and
      fermionic species and to systems where evaporative cooling is not possible.

PMID- 29170238
TI  - Double-trap measurement of the proton magnetic moment at 0.3 parts per billion
      precision.
AB  - Precise knowledge of the fundamental properties of the proton is essential for
      our understanding of atomic structure as well as for precise tests of fundamental
      symmetries. We report on a direct high-precision measurement of the magnetic
      moment MUp of the proton in units of the nuclear magneton MUN The result, MUp =
      2.79284734462 (+/-0.00000000082) MUN, has a fractional precision of 0.3 parts per
      billion, improves the previous best measurement by a factor of 11, and is
      consistent with the currently accepted value. This was achieved with the use of
      an optimized double-Penning trap technique. Provided a similar measurement of the
      antiproton magnetic moment can be performed, this result will enable a test of
      the fundamental symmetry between matter and antimatter in the baryonic sector at
      the 10-10 level.

PMID- 29170239
TI  - Current-induced strong diamagnetism in the Mott insulator Ca2RuO4.
AB  - Mott insulators can host a surprisingly diverse set of quantum phenomena when
      their frozen electrons are perturbed by various stimuli. Superconductivity, metal
      insulator transition, and colossal magnetoresistance induced by element
      substitution, pressure, and magnetic field are prominent examples. Here we report
      strong diamagnetism in the Mott insulator calcium ruthenate (Ca2RuO4) induced by
      dc electric current. The application of a current density of merely 1 ampere per
      centimeter squared induces diamagnetism stronger than that in other
      nonsuperconducting materials. This change is coincident with changes in the
      transport properties as the system becomes semimetallic. These findings suggest
      that dc current may be a means to control the properties of materials in the
      vicinity of a Mott insulating transition.

PMID- 29170240
TI  - Learning to be a mentor.

PMID- 29170241
TI  - How does the canine paw pad attenuate ground impacts? A multi-layer cushion
      system.
AB  - Macroscopic mechanical properties of digitigrade paw pads, such as non-linear
      elastic and variable stiffness, have been investigated in previous studies;
      however, little is known about the micro-scale structural characteristics of
      digitigrade paw pads, or the relationship between these characteristics and the
      exceptional cushioning of the pads. The digitigrade paw pad consists of a multi
      layered structure, which is mainly comprised of a stratified epithelium layer, a
      dermis layer and a subcutaneous layer. The stratified epithelium layer and dermal
      papillae constitute the epidermis layer. Finite element analyses were carried out
      and showed that the epidermis layer effectively attenuated the ground impact
      across impact velocities of 0.05-0.4 m/s, and that the von Mises stresses were
      uniformly distributed in this layer. The dermis layer encompassing the
      subcutaneous layer can be viewed as a hydrostatic system, which can store,
      release and dissipate impact energy. All three layers in the paw pad work as a
      whole to meet the biomechanical requirements of animal locomotion. These findings
      provide insights into the biomechanical functioning of digitigrade paw pads and
      could be used to facilitate bio-inspired, ground-contacting component development
      for robots and machines, as well as contribute to footwear design.

PMID- 29170242
TI  - After 50 years of legal abortion in Great Britain, calls grow for further
      liberalisation.

PMID- 29170243
TI  - Trajectories of prostate-specific antigen after treatment for prostate cancer.
AB  - Prostate-specific antigen (PSA) measurements after primary treatment reflect
      residual tumor burden among men with prostate cancer. Using a mixture model
      analysis, we identified distinct trajectories of post-treatment PSA measurements
      and evaluated their associations with prostate cancer mortality. The study sample
      included 623 US Veterans treated for prostate cancer with curative intent during
      1991-1995; 225 men received surgery and 398 men received radiation therapy. Post
      treatment PSA measurements over a 2-year period for each patient were evaluated
      in latent class mixture models using the SAS TRAJ procedure, and groups of men
      with distinct trajectories of PSA were identified. These groups were then
      assessed for associations with 10-year prostate cancer mortality using
      proportional hazards analysis. Analyses identified three distinct groups
      representing patterns of both initial values and changes in PSA over time-after
      surgery (n=172/31/14) and radiation therapy (n=253/103/22). Men in groups with
      patterns of higher (compared with the group with lowest) PSA values tended to
      have worse survival experience: HRs for prostate cancer mortality were 3.45
      (P=0.18) and 22.7 (P<0.001) for surgery, and 2.70 (P=0.005) and 18.1 (P<0.001)
      for radiation therapy. The results indicate that PSA measurements after surgery
      or radiation therapy with curative intent include groups of men with a diverse
      spectrum of prognosis for prostate cancer mortality. Although contemporary PSA
      levels are lower than those observed in the study sample, the corresponding
      trajectory patterns may become evident shortly after the time of diagnosis and
      treatment.

PMID- 29170244
TI  - Diabetes and pre-eclampsia affecting pregnancy: a retrospective cross-sectional
      study.
AB  - The interaction between pre-eclampsia and diabetes mellitus (DM) is far from
      being completely understood. In this study, we compared normal pregnancies with
      those complicated with pre-eclampsia, gestational DM, and/or pre-existing
      diabetes to assess the effects of hyperglycemia on placental development.
      AnInstitutional Review Board (IRB) approved retrospective cross-sectional study
      with 621 subjects was performed. Statistical analysis was performed using
      Duncan's post hoc test and analysis of variance. Regardless of diabetes status,
      patients with pre-eclampsia delivered prematurely. Patients in the group with pre
      eclampsia and pregestational diabetes delivered much earlier, at 35.0+/-0.4
      weeks, when compared with the patients that had pre-eclampsia with gestational
      diabetes and pre-eclampsia with no diabetes (*P<0.05 for each). Additionally,
      patients with pre-existing diabetes who developed pre-eclampsia delivered smaller
      babies than those with pre-existing diabetes without pre-eclampsia (1.00+/-0.03,
      P<0.05 for each). Pre-existing diabetes with added insult of pre-eclampsia led to
      fetal growth restriction. This outcome validates the understanding that elevated
      glucose earlier in pregnancy alters placentogenesis and leads to fetal growth
      restriction.

PMID- 29170246
TI  - Parallel Pleistocene amphitropical disjunctions of a parasitic plant and its
      host.
AB  - PREMISE OF THE STUDY: Aphyllon is a clade of holoparasites that includes closely
      related North American and South American species parasitic on Grindelia. Both
      Aphyllon (Orobanchaceae) and Grindelia (Asteraceae) have amphitropical
      disjunctions between North America and South America; however, the timing of
      these patterns and the processes to explain them are unknown. METHODS:
      Chronograms for the Orobanchaceae and Grindelia and their relatives were
      constructed using fossil and secondary calibration points, one of which was based
      on the inferred timing of horizontal gene transfer from a papilionoid legume into
      the common ancestor of Orobanche and Phelipanche. Elevated rates of molecular
      evolution in the Orobanchaceae have hindered efforts to determine reliable
      divergence time estimates in the absence of a fossil record. However, using a
      horizontal gene transfer event as a secondary calibration overcomes this
      limitation. These chronograms were used to reconstruct the biogeography of
      Aphyllon, Grindelia, and relatives using a DEC+J model implemented in RevBayes.
      KEY RESULTS: Aphyllon had two amphitropical dispersals from North America to
      South America, while Grindelia had a single dispersal. The dispersal of the
      Aphyllon lineage that is parasitic on Grindelia (0.40 Ma) took place somewhat
      after Grindelia began to diversify in South America (0.93 Ma). Using a secondary
      calibration based on horizontal gene transfer, we infer more recent divergence
      dates of holoparasitic Orobancheae than previous studies. CONCLUSIONS: Parallel
      host-parasite amphitropical disjunctions in Grindelia and Aphyllon illustrate one
      means by which ecological specialization may result in nonindependent patterns of
      diversity in distantly related lineages. Although Grindelia and Aphyllon both
      dispersed to South America recently, Grindelia appears to have diversified more
      extensively following colonization. More broadly, recent Pleistocene glaciations
      probably have also contributed to patterns of diversity and biogeography of
      temperate northern hemisphere Orobancheae. We also demonstrate the utility of
      using horizontal gene transfer events from well-dated clades to calibrate
      parasite phylogenies in the absence of a fossil record.

PMID- 29170247
TI  - Origins of North American arid-land Verbenaceae: More than one way to skin a cat.
AB  - PREMISE OF THE STUDY: Verbenaceae originated and initially diversified in South
      America in wet forest habitats. They have diversified extensively in arid
      habitats in both South and North America. This study aims to understand the
      origin of the North American arid-land members of Verbenaceae. METHODS: A
      phylogenetic approach is used to examine four genera (Aloysia, Citharexylum,
      Glandularia, Verbena) in three distinct clades with representatives in North
      American deserts and disjunct South and North American distributions.
      Phylogenetic analyses were conducted using maximum likelihood and Bayesian
      approaches. Analyses included both plastid and nuclear DNA regions and include
      the first study of Citharexylum and an expanded sampling of tribe Verbeneae
      (Glandularia and Verbena). Ancestral areas were reconstructed for each group. KEY
      RESULTS: North American desert species of Aloysia and Glandularia were likely
      derived from ancestors in arid temperate South America, perhaps by long-distance
      dispersal. The pattern for Verbena was less clear, with evidence from plastid DNA
      implicating an Andean dispersal route to the North American clade, whereas
      nuclear data suggest that the Andean and North American species resulted from
      independent dispersals from southern South America. A previously unrecognized
      clade of Andean Verbeneae was discovered, raising the possibility of an Andean
      origin of Verbena or Verbena and Glandularia. North American desert species of
      Citharexylum represent multiple, independent origins from mesic habitat ancestors
      in Mesoamerica. CONCLUSIONS: North American arid-zone Verbenaceae are derived
      from South and Central American ancestors via multiple avenues, including long
      distance, amphitropical dispersal, Andean migration corridors, and in situ
      evolution of desert-adapted species.

PMID- 29170248
TI  - Memoirs of a frequent flier: Phylogenomics reveals 18 long-distance dispersals
      between North America and South America in the popcorn flowers (Amsinckiinae).
AB  - PREMISE OF THE STUDY: American amphitropical disjunction (AAD) is an important
      but understudied New World biogeographic pattern in which related plants occur in
      extratropical North America and South America, but are absent in the intervening
      tropics. Subtribe Amsinckiinae (Boraginaceae) is one of the richest groups of
      plants displaying the AAD pattern. Here, we infer a time-calibrated molecular
      phylogeny of the group to evaluate the number, timing, and directionality of AAD
      events, which yields generalizable insights into the mechanism of AAD. METHODS:
      We perform a phylogenomic analysis of 139 samples of subtribe Amsinckiinae and
      infer divergence times using two calibration schemes: with only fossil
      calibrations and with fossils plus a secondary calibration from a recent family
      level analysis. Biogeographic analysis was performed in the R package
      BioGeoBEARS. KEY RESULTS: We document 18 examples of AAD in the Amsinckiinae.
      Inferred divergence times of these AAD examples were strongly asynchronous,
      ranging from Miocene (17.1 million years ago [Ma]) to Pleistocene (0.33 Ma), with
      most (12) occurring <5 Ma. Four events occurred 10-5 Ma, during the second rise
      of the Andes. All AAD examples had a North America to South America
      directionality. CONCLUSIONS: Second only to the hyperdiverse Poaceae in number of
      documented AAD examples, the Amsinckiinae is an ideal system for the study of
      AAD. Asynchronous divergence times support the hypothesis of long-distance
      dispersal by birds as the mechanism of AAD in the subtribe and more generally.
      Further comparative phylogenomic studies may permit biogeographic hypothesis
      testing and examination of the relationship between AAD and fruit morphology,
      reproductive biology, and ploidy.

PMID- 29170249
TI  - Lower respiratory infections in early life are linked to later asthma.

PMID- 29170250
TI  - High PDGFRA expression does not serve as an effective therapeutic target in ERG
      deleted B-cell precursor acute lymphoblastic leukemia.

PMID- 29170251
TI  - Clustered F8 missense mutations cause hemophilia A by combined alteration of
      splicing and protein biosynthesis and activity.
AB  - Dissection of pleiotropic effects of missense mutations, rarely investigated in
      inherited diseases, is fundamental to understanding genotype-phenotype
      relationships. Missense mutations might impair mRNA processing in addition to
      protein properties. As a model for hemophilia A, we investigated the highly
      prevalent F8 c.6046c>t/p.R2016W (exon 19) mutation. In expression studies
      exploiting lentiviral vectors, we demonstrated that the amino acid change impairs
      both Factor VIII (FVIII) secretion (antigen 11.0+/-0.4% of wild-type) and
      activity (6.0+/-2.9%). Investigations in patients' ectopic F8 mRNA and with
      minigenes showed that the corresponding nucleotide change also decreases correct
      splicing to 70+/-5%, which is predicted to lower further FVIII activity (4.2+/
      2%), consistently with patients' levels (<1-5%). Masking the mutated exon 19
      region by antisense U7snRNA supported the presence of a splicing regulatory
      element, potentially affected by several missense mutations causing hemophilia A.
      Among these, the c.6037g>a (p.G2013R) reduced exon inclusion to 41+/-3% and the
      c.6053a>g (p.E2018G) to 28+/-2%, similarly to a variant affecting the 5' splice
      site (c.6113a>g, p.N2038S, 26+/-2%), which displayed normal protein features upon
      recombinant expression. The p.G2013R reduced both antigen (7.0+/-0.9%) and
      activity (8.4+/-0.8%), while the p.E2018G produced a dysfunctional molecule
      (antigen: 69.0+/-18.1%; activity: 19.4+/-2.3%). In conclusion, differentially
      altered mRNA and protein patterns produce a gradient of residual activity, and
      clarify genotype-phenotype relationships. Data detail pathogenic mechanisms that,
      only in combination, account for moderate/severe disease forms, which in turn
      determine the mutation profile. Taken together we provide a clear example of
      interplay between mRNA and protein mechanisms of disease that operate in shaping
      many other inherited disorders.

PMID- 29170252
TI  - Nationwide survey on the use of eltrombopag in patients with severe aplastic
      anemia: a report on behalf of the French Reference Center for Aplastic Anemia.
AB  - Few therapeutic options are available for patients with aplastic anemia who are
      ineligible for transplantation or refractory to immunosuppressive therapy.
      Eltrombopag was recently shown to produce trilineage responses in refractory
      patients. However, the effects of real-life use of this drug remain unknown. This
      retrospective study (2012-2016) was conducted by the French Reference Center for
      Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and
      patients ineligible for antithymocyte globulin or transplantation, who received
      eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were
      given eltrombopag without prior antithymocyte globulin treatment (n=11) or after
      antithymocyte globulin administration (n=35) in a relapsed/refractory setting.
      Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50)
      after the diagnosis of aplastic anemia. At last followup, 49% were still
      receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity
      and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients
      received regular transfusions. The overall rates of red blood cell and platelet
      transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last
      follow-up. Responses were slower to develop in antithymocyte treatment-naive
      patients. In patients achieving transfusion independence, hemoglobin
      concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4
      4.5) and 42*109/L (interquartile range, 11-100), respectively. Response in at
      least one lineage (according to National Institutes of Health criteria) was
      observed in 64% of antithymocyte treatment-naive and 74% of relapsed/refractory
      patients, while trilineage improvement was observed in 27% and 34%, respectively.
      We found high rates of hematologic improvement and transfusion independence in
      refractory aplastic anemia patients but also in patients ineligible for
      antithymocyte globulin receiving first-line treatment. In conclusion, elderly
      patients unfit for antithymocyte globulin therapy may benefit from eltrombopag.

PMID- 29170253
TI  - Survival adjusting for crossover: phase 3 study of ibrutinib vs. chlorambucil in
      older patients with untreated chronic lymphocytic leukemia/small lymphocytic
      lymphoma.

PMID- 29170254
TI  - WT1 loss attenuates the TP53-induced DNA damage response in T-cell acute
      lymphoblastic leukemia.
AB  - Loss-of-function mutations and deletions in Wilms tumor 1 (WT1) gene are present
      in approximately 10% of T-cell acute lymphoblastic leukemia. Clinically, WT1
      mutations are enriched in relapsed series and are associated to inferior relapse
      free survival in thymic T-cell acute lymphoblastic leukemia cases. Here we
      demonstrate that WT1 plays a critical role in the response to DNA damage in T
      cell leukemia. WT1 loss conferred resistance to DNA damaging agents and
      attenuated the transcriptional activation of important apoptotic regulators
      downstream of TP53 in TP53-competent MOLT4 T-leukemia cells but not in TP53
      mutant T-cell acute lymphoblastic leukemia cell lines. Notably, WT1 loss
      positively affected the expression of the X-linked inhibitor of apoptosis
      protein, XIAP, and genetic or chemical inhibition with embelin (a XIAP inhibitor)
      significantly restored sensitivity to gamma-radiation in both T-cell acute
      lymphoblastic leukemia cell lines and patient-derived xenografts. These results
      reveal an important role for the WT1 tumor suppressor gene in the response to DNA
      damage, and support the view that anti-XIAP targeted therapies could have a role
      in the treatment of WT1-mutant T-cell leukemia.

PMID- 29170255
TI  - Outcomes among North American patients with diffuse large B-cell lymphoma are
      independent of tumor Epstein-Barr virus positivity or immunosuppression.
AB  - The prevalence, presenting clinical and pathological characteristics, and
      outcomes for patients with diffuse large B-cell lymphoma that is Epstein-Barr
      virus positive remain uncertain as does the impact of congenital or iatrogenic
      immunosuppression. Patients with newly diagnosed diffuse large B-cell lymphoma
      with available tissue arrays were identified from the University of Iowa/Mayo
      Clinic Molecular Epidemiology Resource. Patients infected with human
      immunodeficiency virus or who had undergone a prior organ transplant were
      excluded. Epstein-Barr virus-associated ribonucleic acid testing was performed on
      all tissue arrays. A history of significant congenital or iatrogenic
      immunosuppression was determined for all patients. At enrollment, 16 of the 362
      (4.4%) biopsies were positive for Epstein-Barr virus. Thirty-nine (10.8%)
      patients had a significant history of immunosuppression. Patients with Epstein
      Barr-positive diffuse large B-cell lymphoma had no unique clinical
      characteristics but on pathology exhibited a higher frequency of CD30 positivity
      (25.0% versus 8.1%, respectively; P<0.01), and non-germinal-center subtype (62.5%
      versus 34.1%, respectively; P<0.01). No baseline clinical characteristics were
      associated with a history of immunosuppression. With a median follow up of 59
      months, and after adjustment for International Prognostic Index, there was no
      association of Epstein-Barr virus positivity or immunosuppression with event-free
      survival at 24 months (odds ratio=0.49; 95% confidence interval: 0.13-1.84 and
      odds ratio=0.81; 95% confidence interval: 0.37-1.77) or overall survival (hazard
      ratio=0.86; 95% confidence interval: 0.38-1.97 and hazard ratio=1.00; 95%
      confidence interval: 0.57-1.74). In contrast to non-Western populations, our
      North American population had a low prevalence of Epstein-Barr virus-positive
      diffuse large B-cell lymphoma that did not convey an adverse prognosis. A history
      of immunosuppression, while known to be a risk factor for the development of
      diffuse large B-cell lymphoma, did not affect subsequent prognosis.

PMID- 29170257
TI  - Cognitive skills of common shrews (Sorex araneus) vary with seasonal changes in
      skull size and brain mass.
AB  - In a rare phenomenon, shrews and a few other species cope with seasonal
      environments by reducing and regrowing brain size, potentially at the cost of
      changes in cognitive abilities. Here, we confirm an extensive seasonal shrinkage
      (21.4%) and regrowth (17.0%) of brain mass in winter and spring, respectively, in
      the common shrew (Sorex araneus L.) in Southern Germany. In a spatial learning
      task experiment, individuals with reduced winter brain size covered larger
      distances to find food, compared with the relatively large-brained summer
      juveniles and regrown spring adults. By reducing their brain mass, these shrews
      may reduce their energetic demands, but at the cost of cognitive performance,
      implying a complex trade-off for coping with seasonally fluctuating resources.
      These results are relevant for our understanding of evolution and the dynamics of
      mammalian nervous systems in response to environmental changes.

PMID- 29170256
TI  - Effects of a physical and energetic challenge on male California mice (Peromyscus
      californicus): modulation by reproductive condition.
AB  - Reproduction strongly influences metabolism, morphology and behavior in female
      mammals. In species in which males provide parental care, reproduction might have
      similar effects on fathers. We examined effects of an environmental challenge on
      metabolically important physiological, morphological and behavioral measures, and
      determined whether these effects differed between reproductive and non
      reproductive males in the biparental California mouse (Peromyscus californicus).
      Males were paired with an ovary-intact female, an ovariectomized female treated
      with estrogen and progesterone to induce estrus, or an untreated ovariectomized
      female. Within each group, half of the animals were housed under standard
      laboratory conditions and half in cages requiring them to climb wire towers to
      obtain food and water; these latter animals were also fasted for 24 h every third
      day. We predicted that few differences would be observed between fathers and non
      reproductive males under standard conditions, but that fathers would be in poorer
      condition than non-reproductive males under challenging conditions. Body and fat
      mass showed a housing condition*reproductive group interaction: the challenge
      condition increased body and fat mass in both groups of non-reproductive males,
      but breeding males were unaffected. Males housed under the physical and energetic
      challenge had higher blood lipid content, lower maximal aerobic capacity and
      related traits (hematocrit and relative triceps surae mass), increased pain
      sensitivity and increased number of fecal boli excreted during tail-suspension
      tests (a measure of anxiety), compared with controls. Thus, our physical and
      energetic challenge paradigm altered metabolism, morphology and behavior, but
      these effects were largely unaffected by reproductive condition.

PMID- 29170258
TI  - Mechanisms for the functional differentiation of the propulsive and braking roles
      of the forelimbs and hindlimbs during quadrupedal walking in primates and
      felines.
AB  - During quadrupedal walking in most animals, the forelimbs play a net braking
      role, whereas the hindlimbs are net propulsive. However, the mechanism by which
      this differentiation occurs remains unclear. Here, we test two models to explain
      this pattern using primates and felines: (1) the horizontal strut effect (in
      which limbs are modeled as independent struts), and (2) the linked strut model
      (in which limbs are modeled as linked struts with a center of mass in between).
      Video recordings were used to determine point of contact, timing of mid-stance,
      and limb protraction/retraction duration. Single-limb forces were used to
      calculate contact time, impulses and the proportion of the stride at which the
      braking-to-propulsive transition (BP) occurred for each limb. We found no
      association between the occurrence of the BP and mid-stance, little influence of
      protraction and retraction duration on the braking-propulsive function of a limb,
      and a causative relationship between vertical force distribution between limbs
      and the patterns of horizontal forces. These findings reject the horizontal strut
      effect, and provide some support for the linked strut model, although predictions
      were not perfectly matched. We suggest that the position of the center of mass
      relative to limb contact points is a very important, but not the only, factor
      driving functional differentiation of the braking and propulsive roles of the
      limbs in quadrupeds. It was also found that primates have greater differences in
      horizontal impulse between their limbs compared with felines, a pattern that may
      reflect a fundamental arboreal adaptation in primates.

PMID- 29170259
TI  - Sound production mechanism in triggerfish (Balistidae): a synapomorphy.
AB  - The ability to produce sounds for acoustic communication is known in different
      Balistidae species but the eventual synapomorphic aspect of the mechanism remains
      to be shown. In Rhinecanthus aculeatus, sounds result from alternate sweeping
      movements of the right and left pectoral fins, which push a system of three
      scutes against the swim bladder wall. In this study, we made a comparison between
      the sounds produced by this species and two additional ones (Balistapus undulatus
      and Rhinecanthus rectangulus) using hand-held specimens to provide a description
      of the sound mechanism. The results highlighted that the sound production
      mechanism is similar in the three species. According to recent phylogenetic data
      and shared morphological features, this mechanism could be common to the majority
      of Balistidae family members and all species could be capable of sound production
      using pectoral fins.

PMID- 29170260
TI  - Multimodal sensorimotor system in unicellular zoospores of a fungus.
AB  - Complex sensory systems often underlie critical behaviors, including avoiding
      predators and locating prey, mates and shelter. Multisensory systems that control
      motor behavior even appear in unicellular eukaryotes, such as Chlamydomonas,
      which are important laboratory models for sensory biology. However, we know of no
      unicellular opisthokonts that control motor behavior using a multimodal sensory
      system. Therefore, existing single-celled models for multimodal sensorimotor
      integration are very distantly related to animals. Here, we describe a
      multisensory system that controls the motor function of unicellular fungal
      zoospores. We found that zoospores of Allomyces arbusculus exhibit both
      phototaxis and chemotaxis. Furthermore, we report that closely related Allomyces
      species respond to either the chemical or the light stimuli presented in this
      study, not both, and likely do not share this multisensory system. This diversity
      of sensory systems within Allomyces provides a rare example of a comparative
      framework that can be used to examine the evolution of sensory systems following
      the gain/loss of available sensory modalities. The tractability of Allomyces and
      related fungi as laboratory organisms will facilitate detailed mechanistic
      investigations into the genetic underpinnings of novel photosensory systems, and
      how multisensory systems may have functioned in early opisthokonts before
      multicellularity allowed for the evolution of specialized cell types.

PMID- 29170261
TI  - Transitions and prospects.

PMID- 29170262
TI  - Subsequent Injury Study (SInS): Improving outcomes for injured New Zealanders.
AB  - BACKGROUND: Subsequent injury (SI) is a major contributor to disability and costs
      for individuals and society. AIM: To identify modifiable risk factors predictive
      of SI and SI health and disability outcomes and costs. OBJECTIVES: To (1)
      describe the nature of SIs reported to New Zealand's no-fault injury insurer (the
      Accident Compensation Corporation (ACC)); (2) identify characteristics of people
      underaccessing ACC for SI; (3) determine factors predicting or protecting against
      SI; and (4) investigate outcomes for individuals, and costs to society, in
      relation to SI. DESIGN: Prospective cohort study. METHODS: Previously collected
      data will be linked including data from interviews undertaken as part of the
      earlier Prospective Outcomes of Injury Study (POIS), ACC electronic data and
      national hospitalisation data about SI. POIS participants (N=2856, including 566
      Maori) were recruited via ACC's injury register following an injury serious
      enough to warrant compensation entitlements. We will examine SI over the
      following 24 months for these participants using descriptive and inferential
      statistics including multivariable generalised linear models and Cox's
      proportional hazards regression. DISCUSSION: Subsequent Injury Study (SInS) will
      deliver information about the risks, protective factors and outcomes related to
      SI for New Zealanders. As a result of sourcing injury data from New Zealand's
      'all injury' insurer ACC, SInS includes people who have been hospitalised and not
      hospitalised for injury. Consequently, SInS will provide insights that are novel
      internationally as other studies are usually confined to examining trauma
      registries, specific injuries or injured workers who are covered by a workplace
      insurer rather than a 'real-world' injury population.

PMID- 29170263
TI  - A man with paraesthesia, headache, and vertigo.

PMID- 29170264
TI  - Non-hormonal treatments for menopausal symptoms.

PMID- 29170265
TI  - New test in tribunal cases could find more doctors acted dishonestly.

PMID- 29170266
TI  - Posttreatment Infarct Volumes when Compared with 24-Hour and 90-Day Clinical
      Outcomes: Insights from the REVASCAT Randomized Controlled Trial.
AB  - BACKGROUND AND PURPOSE: Endovascular therapy has become the standard of care for
      patients with disabling anterior circulation ischemic stroke due to proximal
      intracranial thrombi. Our aim was to determine whether the beneficial effect of
      endovascular treatment on functional outcome could be explained by a reduction in
      posttreatment infarct volume in the Endovascular Revascularization With Solitaire
      Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours
      (REVASCAT) trial. MATERIALS AND METHODS: The REVASCAT trial was a multicenter
      randomized open-label trial with blinded outcome evaluation. Among 206 enrolled
      subjects (endovascular treatment, n = 103; control, n = 103), posttreatment
      infarct volume was measured in 204 subjects. Posttreatment infarct volumes were
      compared with treatment assignment and recanalization status. Appropriate
      statistical models were used to assess the relationship among baseline clinical
      and imaging variables, posttreatment infarct volume, the 24-hour NIHSS score, and
      functional status with the 90-day modified Rankin Scale score. RESULTS: The
      median posttreatment infarct volume in all subjects was 23.7 mL (interquartile
      range = 68.9 mL) and 16.3 mL (interquartile range = 50.2 mL) in the endovascular
      treatment arm and 38.6 mL (interquartile range = 74.9 mL) in the control arm (P =
      .02 for endovascular treatment versus control subjects). Baseline NIHSS (P <
      .01), site of occlusion (P < .03), baseline NCCT ASPECTS (P < .01), and
      recanalization status (P = .02) were independently associated with posttreatment
      infarct volume. Baseline NIHSS (P < .01), time from symptom onset to
      randomization (P = .02), treatment type (P = .04), and recanalization status (P <
      .01) were independently associated with the 24-hour NIHSS scores. The 24-hour
      NIHSS score strongly mediated the relationship between treatment type and 90-day
      mRS (P < .01 for indirect effect when adjusted for age), while posttreatment
      infarct volume did not (P = .26). CONCLUSIONS: Endovascular treatment saves brain
      and improves 90-day clinical outcomes primarily through a beneficial effect on
      the 24-hour stroke severity.

PMID- 29170267
TI  - Perivascular Spaces in Old Age: Assessment, Distribution, and Correlation with
      White Matter Hyperintensities.
AB  - BACKGROUND AND PURPOSE: The visual rating scales for perivascular spaces vary
      considerably. We sought to develop a new scale for visual assessment of
      perivascular spaces and to further describe their distribution and association
      with white matter hyperintensities in old age. MATERIALS AND METHODS: This
      population-based study included 530 individuals who did not have dementia and
      were not institutionalized (age, >=60 years or older; mean age, 70.7 years; 58.9%
      women) who were living in central Stockholm, Sweden. A semiquantitative visual
      rating scale was developed to score the number and size of visible perivascular
      spaces in 7 brain regions in each hemisphere. A modified Scheltens visual rating
      scale was used to assess white matter hyperintensities. RESULTS: The global
      scores for perivascular spaces ranged from 4-32 for number, 3-22 for size, and 7
      54 for the combination of number and size. The weighted kappa statistics for the
      intra- and interrater reliability both were 0.77. The global score for the number
      of perivascular spaces increased with advancing age (P < .001). The scores for
      the number of perivascular spaces in the basal ganglia and subinsular regions
      were significantly correlated with the load of white matter hyperintensities,
      especially in lobar and deep white matter regions (partial correlation
      coefficients, >0.223; P < .01). CONCLUSIONS: The new visual rating scale for
      perivascular spaces shows excellent intra- and interrater reliability. The number
      of perivascular spaces globally and, especially, in the basal ganglia, is
      correlated with the load of lobar and deep white matter hyperintensities,
      supporting the view that perivascular spaces are a marker for cerebral small
      vessel disease.

PMID- 29170268
TI  - Leukoaraiosis Attenuates Diagnostic Accuracy of Large-Vessel Occlusion Scales.
AB  - BACKGROUND AND PURPOSE: Prehospital stroke scales may help identify patients
      likely to have large-vessel occlusion to facilitate rapid triage to thrombectomy
      capable stroke centers. Scale misclassification may result in inaccurate
      decisions and possible harm. Pre-existing leukoaraiosis has been shown to
      attenuate the association between deficit type and stroke severity. We sought to
      determine whether leukoaraiosis affects the predictive ability of 5 commonly used
      large-vessel occlusion scales. MATERIALS AND METHODS: We retrospectively analyzed
      274 consecutive patients with stroke with available brain MR imaging and vessel
      imaging. We used the following large-vessel occlusion scales: the 3-Item Stroke
      Scale; Field Assessment Stroke Triage for Emergency Destination; Rapid Arterial
      Occlusion Evaluation; Vision, Aphasia, Neglect score; and Cincinnati Prehospital
      Stroke Severity Scale. For diagnostic scale accuracy, we assessed sensitivity,
      specificity, positive predictive value, negative predictive value, and kappa.
      Multivariable logistic regression was used to determine the predictive ability of
      the scales after adjustment for leukoaraiosis and potential confounders. RESULTS:
      In unadjusted analyses, all scales predicted the presence of large-vessel
      occlusion (n = 46, P < .01 each), though diagnostic accuracy was attenuated among
      patients with moderate-to-severe leukoaraiosis. After adjustment, the Field
      Assessment Stroke Triage for Emergency Destination (OR = 3.2; 95% CI, 1.1-9.5; P
      = .033) and Rapid Arterial Occlusion Evaluation (OR = 3.7; 95% CI, 1.3-10.8; P =
      .015), but not the 3-Item Stroke Scale (OR = 5.4; 95% CI, 0.86-33.9; P = .073),
      Vision, Aphasia, Neglect score (OR = 2.5; 95% CI, 0.8-7.2), and Cincinnati
      Prehospital Stroke Severity Scale (OR = 2.8; 95% CI, 1.0-8.0), predicted large
      vessel occlusion. CONCLUSIONS: The diagnostic accuracy of the tested large-vessel
      occlusion scales was attenuated in the presence of moderate-to-severe
      leukoaraiosis. This information that may aid the design of future studies that
      require large-vessel occlusion scale screening of patients who are likely to have
      concomitant leukoaraiosis.

PMID- 29170269
TI  - Feasibility of Brain Atrophy Measurement in Clinical Routine without Prior
      Standardization of the MRI Protocol: Results from MS-MRIUS, a Longitudinal
      Observational, Multicenter Real-World Outcome Study in Patients with Relapsing
      Remitting MS.
AB  - BACKGROUND AND PURPOSE: Feasibility of brain atrophy measurement in patients with
      MS in clinical routine, without prior standardization of the MRI protocol, is
      unknown. Our aim was to investigate the feasibility of brain atrophy measurement
      in patients with MS in clinical routine. MATERIALS AND METHODS: Multiple
      Sclerosis and Clinical Outcome and MR Imaging in the United States (MS-MRIUS) is
      a multicenter (33 sites), retrospective study that included patients with
      relapsing-remitting MS who began treatment with fingolimod. Brain MR imaging
      examinations previously acquired at the baseline and follow-up periods on 1.5T or
      3T scanners with no prior standardization were used, to resemble a real-world
      situation. Brain atrophy outcomes included the percentage brain volume change
      measured by structural image evaluation with normalization of atrophy on 2D-T1
      weighted imaging and 3D-T1WI and the percentage lateral ventricle volume change,
      measured by VIENA on 2D-T1WI and 3D-T1WI and NeuroSTREAM on T2-fluid-attenuated
      inversion recovery examinations. RESULTS: A total of 590 patients, followed for
      16 months, were included. There were 585 (99.2%) T2-FLAIR, 425 (72%) 2D-T1WI, and
      166 (28.2%) 3D-T1WI longitudinal pairs of examinations available. Excluding MR
      imaging examinations with scanner changes, the analyses were available on 388
      (65.8%) patients on T2-FLAIR for the percentage lateral ventricle volume change,
      259 and 257 (43.9% and 43.6%, respectively) on 2D-T1WI for the percentage brain
      volume change and the percentage lateral ventricle volume change, and 110 (18.6%)
      on 3D-T1WI for the percentage brain volume change and percentage lateral
      ventricle volume change. The median annualized percentage brain volume change was
      -0.31% on 2D-T1WI and -0.38% on 3D-T1WI. The median annualized percentage lateral
      ventricle volume change was 0.95% on 2D-T1WI, 1.47% on 3D-T1WI, and 0.90% on T2
      FLAIR. CONCLUSIONS: Brain atrophy was more readily assessed by estimating the
      percentage lateral ventricle volume change on T2-FLAIR compared with the
      percentage brain volume change or percentage lateral ventricle volume change
      using 2D- or 3D-T1WI in this observational retrospective study. Although
      measurement of the percentage brain volume change on 3D-T1WI remains the
      criterion standard and should be encouraged in future prospective studies, T2
      FLAIR-derived percentage lateral ventricle volume change may be a more feasible
      surrogate when historical or other practical constraints limit the availability
      of percentage brain volume change on 3D-T1WI.

PMID- 29170270
TI  - The Role of Hemodynamics in Intracranial Bifurcation Arteries after Aneurysm
      Treatment with Flow-Diverter Stents.
AB  - BACKGROUND AND PURPOSE: Treatment of intracranial bifurcation aneurysms with flow
      diverter stents can lead to caliber changes of the distal vessels in a subacute
      phase. This study aims to evaluate whether local anatomy and flow disruption
      induced by flow-diverter stents are associated with vessel caliber changes in
      intracranial bifurcations. MATERIALS AND METHODS: Radiologic images and
      demographic data were acquired for 25 patients with bifurcation aneurysms treated
      with flow-diverter stents. Whisker plots and Mann-Whitney rank sum tests were
      used to evaluate if anatomic data and caliber changes could be linked.
      Symmetry/asymmetry were defined as diameter ratio 1 = symmetric and diameter
      ratio <1 = asymmetric. Computational fluid dynamics was performed on idealized
      and patient-specific anatomies to evaluate flow changes induced by flow-diverter
      stents in the jailed vessel. RESULTS: Statistical analysis identified a marked
      correspondence between asymmetric bifurcation and caliber change. Symmetry ratios
      were lower for cases showing narrowing or subacute occlusion (medium daughter
      vessel diameter ratio = 0.59) compared with cases with posttreatment caliber
      conservation (medium daughter vessel diameter ratio = 0.95). Computational fluid
      dynamics analysis in idealized and patient-specific anatomies showed that wall
      shear stress in the jailed vessel was more affected when flow-diverter stents
      were deployed in asymmetric bifurcations (diameter ratio <0.65) and less affected
      when deployed in symmetric anatomies (diameter ratio ~1.00). CONCLUSIONS:
      Anatomic data analysis showed statistically significant correspondence between
      caliber changes and bifurcation asymmetry characterized by diameter ratio <0.7 (P
      < .001). Similarly, computational fluid dynamics results showed the highest
      impact on hemodynamics when flow-diverter stents are deployed in asymmetric
      bifurcations (diameter ratio <0.65) with noticeable changes on wall sheer stress
      fields. Further research and clinical validation are necessary to identify all
      elements involved in vessel caliber changes after flow-diverter stent procedures.

PMID- 29170271
TI  - Temporal Lobe Malformations in Achondroplasia: Expanding the Brain Imaging
      Phenotype Associated with FGFR3-Related Skeletal Dysplasias.
AB  - Thanatophoric dysplasia, achondroplasia, and hypochondroplasia belong to the
      fibroblast growth factor receptor 3 (FGFR3) group of genetic skeletal disorders.
      Temporal lobe abnormalities have been documented in thanatophoric dysplasia and
      hypochondroplasia, and in 1 case of achondroplasia. We retrospectively identified
      13 children with achondroplasia who underwent MR imaging of the brain between
      2002 and 2015. All children demonstrated a deep transverse temporal sulcus on MR
      imaging. Further common neuroimaging findings were incomplete hippocampal
      rotation (12 children), oversulcation of the mesial temporal lobe (11 children),
      loss of gray-white matter differentiation of the mesial temporal lobe (5
      children), and a triangular shape of the temporal horn (6 children). These
      appearances are very similar to those described in hypochondroplasia,
      strengthening the association of temporal lobe malformations in FGFR3-associated
      skeletal dysplasias.

PMID- 29170272
TI  - Vertebroplasty and Kyphoplasty for Osteoporotic Vertebral Fractures: What Are the
      Latest Data?
AB  - Osteoporotic vertebral compression fractures frequently result in significant
      morbidity and health care resource use. For patients with severe and disabling
      pain, vertebral augmentation (vertebroplasty and kyphoplasty) is often
      considered. Although vertebroplasty was introduced >30 years ago, there are
      conflicting opinions regarding the role of these procedures in the treatment of
      osteoporotic vertebral compression fractures. This review article updates
      clinicians on the published prospective randomized controlled data, including the
      most recent positive trials that followed initial negative trials in 2009.
      Analysis of multiple national claim datasets has also provided further insight
      into the utility of these procedures. Finally, we considered the recent
      recommendations of national organizations and medical societies that advise on
      the use of vertebral augmentation procedures for osteoporotic vertebral
      compression fractures.

PMID- 29170274
TI  - Reply.

PMID- 29170273
TI  - Optimization of Quantitative Dynamic Postgadolinium MRI Technique Using
      Normalized Ratios for the Evaluation of Temporomandibular Joint Synovitis in
      Patients with Juvenile Idiopathic Arthritis.
AB  - BACKGROUND AND PURPOSE: MR imaging has been shown to be useful in the diagnosis
      of juvenile idiopathic arthritis of the temporomandibular joint. Prior MR imaging
      approaches have relied mainly on the subjective interpretation of synovial
      enhancement as a marker for synovial inflammation. Although, more recently,
      several attempts have been made to quantify synovial enhancement, these methods
      have not taken into account the dynamic enhancement characteristics of the
      temporomandibular joint and the effect of sampling time. Our aim was to develop a
      clinically feasible, reproducible, dynamic, contrast-enhanced MR imaging
      technique for the quantitative assessment of temporomandibular joint synovitis in
      patients with juvenile idiopathic arthritis and to study the effect of sampling
      time on the evaluation of synovitis. MATERIALS AND METHODS: This was a
      retrospective study of all patients who had dynamic, contrast-enhanced coronal T1
      3T MR imaging through the temporomandibular joint at our institution between
      January 1, 2015, and July 8, 2016. Patients in this cohort included those with a
      history of juvenile idiopathic arthritis and control patients who underwent MR
      imaging for other routine, clinical purposes. Synovial enhancement was calculated
      for each temporomandibular joint using 3 different types of equations termed
      normalization ratios. The enhancement profiles generated by each equation were
      studied to determine which provided the best discrimination between affected and
      unaffected joints, was the least susceptible to sampling errors, and was the most
      clinically feasible. RESULTS: A ratio of synovial enhancement (defined as the
      difference between the postgadolinium and the pregadolinium T1 signal of the
      synovium) to the postgadolinium signal of the longus capitis provided the best
      discrimination between affected and unaffected joints, the least susceptibility
      to sampling error, and was thought to be the most clinically feasible method of
      quantification of synovial inflammation. Additional synovial enhancement ratios
      studied did not provide the same level rates of discrimination between the
      affected and unaffected joints and were thought to be too temporally variable to
      provide reliable clinical use. CONCLUSIONS: We provide a robust, reproducible,
      dynamic gadolinium-enhanced MR imaging technique for the quantitative assessment
      of temporomandibular joint synovitis in patients with juvenile idiopathic
      arthritis.

PMID- 29170275
TI  - Concerns about a New Preterm MR Imaging Scoring System.

PMID- 29170276
TI  - Seven days in medicine: 15-21 November 2017.

PMID- 29170277
TI  - Rapid hybrid speciation in Darwin's finches.
AB  - Homoploid hybrid speciation in animals has been inferred frequently from patterns
      of variation, but few examples have withstood critical scrutiny. Here we report a
      directly documented example, from its origin to reproductive isolation. An
      immigrant Darwin's finch to Daphne Major in the Galapagos archipelago initiated a
      new genetic lineage by breeding with a resident finch (Geospiza fortis). Genome
      sequencing of the immigrant identified it as a G. conirostris male that
      originated on Espanola >100 kilometers from Daphne Major. From the second
      generation onward, the lineage bred endogamously and, despite intense inbreeding,
      was ecologically successful and showed transgressive segregation of bill
      morphology. This example shows that reproductive isolation, which typically
      develops over hundreds of generations, can be established in only three.

PMID- 29170278
TI  - A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome
      segregation.
AB  - The ataxia telangiectasia mutated and Rad3-related (ATR) kinase is crucial for
      DNA damage and replication stress responses. Here, we describe an unexpected role
      of ATR in mitosis. Acute inhibition or degradation of ATR in mitosis induces
      whole-chromosome missegregation. The effect of ATR ablation is not due to altered
      cyclin-dependent kinase 1 (CDK1) activity, DNA damage responses, or unscheduled
      DNA synthesis but to loss of an ATR function at centromeres. In mitosis, ATR
      localizes to centromeres through Aurora A-regulated association with centromere
      protein F (CENP-F), allowing ATR to engage replication protein A (RPA)-coated
      centromeric R loops. As ATR is activated at centromeres, it stimulates Aurora B
      through Chk1, preventing formation of lagging chromosomes. Thus, a mitosis
      specific and R loop-driven ATR pathway acts at centromeres to promote faithful
      chromosome segregation, revealing functions of R loops and ATR in suppressing
      chromosome instability.

PMID- 29170279
TI  - Multiplex recording of cellular events over time on CRISPR biological tape.
AB  - Although dynamics underlie many biological processes, our ability to robustly and
      accurately profile time-varying biological signals and regulatory programs
      remains limited. Here we describe a framework for storing temporal biological
      information directly in the genomes of a cell population. We developed a
      "biological tape recorder" in which biological signals trigger intracellular DNA
      production that is then recorded by the CRISPR-Cas adaptation system. This
      approach enables stable recording over multiple days and accurate reconstruction
      of temporal and lineage information by sequencing CRISPR arrays. We further
      demonstrate a multiplexing strategy to simultaneously record the temporal
      availability of three metabolites (copper, trehalose, and fucose) in the
      environment of a cell population over time. This work enables the temporal
      measurement of dynamic cellular states and environmental changes and suggests new
      applications for chronicling biological events on a large scale.

PMID- 29170281
TI  - Synthesis of ultrasmall, homogeneously alloyed, bimetallic nanoparticles on
      silica supports.
AB  - Supported nanoparticles containing more than one metal have a variety of
      applications in sensing, catalysis, and biomedicine. Common synthesis techniques
      for this type of material often result in large, unalloyed nanoparticles that
      lack the interactions between the two metals that give the particles their
      desired characteristics. We demonstrate a relatively simple, effective,
      generalizable method to produce highly dispersed, well-alloyed bimetallic
      nanoparticles. Ten permutations of noble and base metals (platinum, palladium,
      copper, nickel, and cobalt) were synthesized with average particle sizes from 0.9
      to 1.4 nanometers, with tight size distributions. High-resolution imaging and x
      ray analysis confirmed the homogeneity of alloying in these ultrasmall
      nanoparticles.

PMID- 29170280
TI  - Analysis of Fusobacterium persistence and antibiotic response in colorectal
      cancer.
AB  - Colorectal cancers comprise a complex mixture of malignant cells, nontransformed
      cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent
      bacterial species in colorectal cancer tissues. Here we show that colonization of
      human colorectal cancers with Fusobacterium and its associated microbiome
      including Bacteroides, Selenomonas, and Prevotella species-is maintained in
      distal metastases, demonstrating microbiome stability between paired primary and
      metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is
      predominantly associated with cancer cells in the metastatic lesions. Mouse
      xenografts of human primary colorectal adenocarcinomas were found to retain
      viable Fusobacterium and its associated microbiome through successive passages.
      Treatment of mice bearing a colon cancer xenograft with the antibiotic
      metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall
      tumor growth. These observations argue for further investigation of antimicrobial
      interventions as a potential treatment for patients with Fusobacterium-associated
      colorectal cancer.

PMID- 29170282
TI  - Histone methyltransferase SUV39H1 participates in host defense by methylating
      mycobacterial histone-like protein HupB.
AB  - Host cell defense against an invading pathogen depends upon various
      multifactorial mechanisms, several of which remain undiscovered. Here, we report
      a novel defense mechanism against mycobacterial infection that utilizes the
      histone methyltransferase, SUV39H1. Normally, a part of the host chromatin,
      SUV39H1, was also found to be associated with the mycobacterial bacilli during
      infection. Its binding to bacilli was accompanied by trimethylation of the
      mycobacterial histone-like protein, HupB, which in turn reduced the cell adhesion
      capability of the bacilli. Importantly, SUV39H1-mediated methylation of HupB
      reduced the mycobacterial survival inside the host cell. This was also true in
      mice infection experiments. In addition, the ability of mycobacteria to form
      biofilms, a survival strategy of the bacteria dependent upon cell-cell adhesion,
      was dramatically reduced in the presence of SUV39H1. Thus, this novel defense
      mechanism against mycobacteria represents a surrogate function of the epigenetic
      modulator, SUV39H1, and operates by interfering with their cell-cell adhesion
      ability.

PMID- 29170283
TI  - Local anaesthetics combined with vasoconstrictors in patients with cardiovascular
      disease undergoing dental procedures: systematic review and meta-analysis
      protocol.
AB  - INTRODUCTION: The use of vasoconstrictors combined with local anaesthetics (LAs)
      in dentistry for patients with cardiovascular disease (CVD) is still
      controversial in the scientific literature. It raises concerns regarding the
      possibility of transient episodes, triggering negative cardiovascular outcomes.
      METHOD/DESIGN: Trials eligible for our systematic review will enrol patients with
      CVD who have undergone dental treatments carried out with the use of LAs by
      comparing two arms: LAs with vasoconstrictors and LAs without vasoconstrictors.
      The research will be conducted in the electronic databases, namely Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Healthstar (via
      Ovid), Cumulative Index to Nursing and Allied Health Literature and Web of
      Science, from their inception to December 2017, without any restrictions in terms
      of language and status of publication. A team of reviewers will independently
      assess titles, abstracts and complete text to determine eligibility. For eligible
      studies, the same reviewers will perform data extraction and evaluate the risk of
      bias in the selected articles. The selected outcomes comprise death, mortality by
      a specific cause, stroke, acute myocardial infarction, hospitalisation, pain,
      bleeding, arrhythmias, ischaemic episodes, anxiety, adverse effects, changes in
      blood pressure, changes in heart rate, anxiety and results obtained via oximetry.
      Whenever possible, we will conduct a meta-analysis to establish the effects of
      LAs with and without vasoconstrictors in the patients with CVD, and the overall
      quality of evidence for each outcome will be determined using the Grading of
      Recommendations Assessment, Development and Evaluation classification system.
      ETHICS AND DISSEMINATION: Ethics committee approval was not necessary because
      this is a protocol of systematic review. This systematic review will be submitted
      for presentation at conferences and for publication in a peer-reviewed journal.
      Our review will assess the risks of cardiovascular events when using LAs with and
      without vasoconstrictors in patients with CVD, focusing on important clinical
      outcomes. PROSPERO REGISTRATION NUMBER: CRD42016045421.

PMID- 29170284
TI  - Impact of multimorbidity on healthcare professional task shifting potential in
      patients with type 2 diabetes in primary care: a French cross-sectional study.
AB  - OBJECTIVES: To estimate the transferability of processes of care from general
      practitioners (GPs) to allied healthcare professionals and the determinants of
      such transferability. DESIGN: French national cross-sectional multicentre study
      SETTING: 128 family practices providing supervised training for residents in
      general practice. PARTICIPANTS: All patients consulting with their GP over a
      total number of 20 days (ie, 1 day a week from December 2011 to April 2012).
      Encounters where type 2 diabetes was one of the managed health problems were
      selected for analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Processes that
      were associated with specific health problems were collected by 54 residents.
      Potential process transferability was the main outcome assessed, as well as the
      professionals involved in the collaboration and the eventual conditions
      associated with transfer. RESULTS: From 8572 processes of care that concerned
      1088 encounters of patients with diabetes, 21.9% (95% CI 21.1% to 22.8%) were
      considered eligible for transfer from GPs to allied healthcare professionals
      (78.1% to nurses, 36.7% to pharmacists). Processes were transferable with
      condition(s) for 70.6% (ie, a protocol, shared record or supervision). The most
      transferable processes concerned health maintenance (32.1%) and cardiovascular
      risk factors (hypertension (28.7%), dyslipidaemia (25.3%) and diabetes (24.3%)).
      Multivariate analysis showed that educational processes or a long-term condition
      status were associated with increased transferability (OR 3.26 and 1.47,
      respectively), whereas patients with higher intellectual occupations or those
      with two or more associated health problems were associated with lower
      transferability (OR 0.33 and 0.81, respectively). CONCLUSIONS: A significant part
      of GP activity relating to patients with multimorbidity including type 2 diabetes
      could be transferred to allied healthcare professionals, mainly on prevention and
      global education to cardiovascular risk factors. The organisational and finance
      conditions of team work as views of patients and healthcare professionals must be
      explored before implementation in primary care.

PMID- 29170285
TI  - Categorising cancers to enable tailored care planning through a secondary
      analysis of cancer registration data in the UK.
AB  - OBJECTIVES: The aim of this study is to categorise cancers into broad groups
      based on clusters of common treatment aims, experiences and outcomes to provide a
      numerical framework for understanding the services required to meet the needs of
      people with different cancers. This framework will enable a high-level overview
      of care and support requirements for the whole cancer population. SETTING AND
      PARTICIPANTS: People in the UK with 1 of 20 common cancers; an estimated 309 000
      diagnoses in 2014, 1 679 000 people diagnosed in a 20-year period and still
      living in 2010 and 135 000 cancer deaths in 2014. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Survival and stage at diagnosis data were reviewed alongside clinically
      led assumptions to identify commonalities and cluster cancer types into three
      groups. The three cancer groups were then described using incidence, prevalence
      and mortality data collected and reported by UK cancer registries. This was then
      reviewed, validated and refined following consultation. RESULTS: Group 1 includes
      cancers with the highest survival; 5-year survival is over 80%. Group 3 cancers
      have shorter term survival. Five-year survival is not >20% for any cancer in this
      group and many do not survive over a year. Group 2 includes cancers where people
      typically live more than a year but are less likely to live >5 years. We estimate
      that the majority (64%) of people living with cancer (20 year prevalence) have a
      cancer type in group 1 'longer term survival', but significant minorities of
      people have cancers in group 2 'intermediate survival' (19%) and group 3 'shorter
      term survival' (10%). CONCLUSIONS: Every person with cancer has unique needs
      shaped by a multitude of factors including comorbidities, treatment regimens,
      patient preferences, needs, attitudes and behaviours. However, to deliver
      personalised care, there needs to be a high-level view of potential care
      requirements to support service planning.

PMID- 29170286
TI  - The effect of nut consumption on markers of inflammation and endothelial
      function: a systematic review and meta-analysis of randomised controlled trials.
AB  - OBJECTIVES: To examine the effect of nut consumption on inflammatory biomarkers
      and endothelial function. DESIGN: A systematic review and meta-analysis. DATA
      SOURCES: MEDLINE, PubMed, Cumulative Index to Nursing and Allied Health
      Literature and Cochrane Central Register of Controlled Trials (all years to 13
      January 2017). ELIGIBILITY CRITERIA: Randomised controlled trials (with a
      duration of 3 weeks or more) or prospective cohort designs conducted in adults;
      studies assessing the effect of consumption of tree nuts or peanuts on C-reactive
      protein (CRP), adiponectin, tumour necrosis factor alpha, interleukin-6,
      intercellular adhesion molecule 1, vascular cell adhesion protein 1 and flow
      mediated dilation (FMD). DATA EXTRACTION AND ANALYSIS: Relevant data were
      extracted for summary tables and analyses by two independent researchers. Random
      effects meta-analyses were conducted to explore weighted mean differences (WMD)
      in change or final mean values for each outcome. RESULTS: A total of 32 studies
      (all randomised controlled trials) were included in the review. The effect of nut
      consumption on FMD was explored in nine strata from eight studies (involving 652
      participants), with consumption of nuts resulting in significant improvements in
      FMD (WMD: 0.79%(95% CI 0.35 to 1.23)). Nut consumption resulted in small, non
      significant differences in CRP (WMD: -0.01 mg/L (95% CI -0.06 to 0.03)) (26
      strata from 25 studies), although sensitivity analyses suggest results for CRP
      may have been influenced by two individual studies. Small, non-significant
      differences were also found for other biomarkers of inflammation. CONCLUSIONS:
      This systematic review and meta-analysis of the effects of nut consumption on
      inflammation and endothelial function found evidence for favourable effects on
      FMD, a measure of endothelial function. Non-significant changes in other
      biomarkers indicate a lack of consistent evidence for effects of nut consumption
      on inflammation. The findings of this analysis suggest a need for more research
      in this area, with a particular focus on randomised controlled trials. PROSPERO
      REGISTRATION NUMBER: CRD42016045424.

PMID- 29170287
TI  - Maternal and neonatal outcomes of vaginal breech delivery for singleton term
      pregnancies in a carefully selected Cameroonian population: a cohort study.
AB  - BACKGROUND AND OBJECTIVES: Vaginal breech delivery (VBD) is known to be
      associated with more perinatal and maternal complications. Very few studies on
      the subject have been carried out in poor-resource settings. The aim of this
      study was to determine maternal and neonatal outcomes in carefully selected cases
      of VBD for singleton term pregnancies in a tertiary centre in Cameroon. DESIGN: A
      retrospective cohort study. SETTING: A tertiary hospital in Yaounde, Cameroon.
      PARTICIPANTS: Cases of VBD of newborns weighing 2500-3500 g were matched in a
      ratio of 1:4 to consecutive vaginal cephalic deliveries (VCDs) of newborns
      weighing 2500-3500 g over a 5-year period. Both groups were matched for maternal
      age and parity. We excluded cases of multiple gestations, footling breech,
      clinically inadequate maternal pelvis, preterm delivery, post-term pregnancies,
      fetal demise prior to the onset of labour, placenta praevia and fetal anomaly
      incompatible with vaginal delivery. OUTCOME MEASURES: Neonatal and maternal
      adverse outcomes of VBD observed till 6 weeks after delivery analysed using
      Bonferroni correction. RESULTS: Fifty-three (53) VBDs were matched against 212
      VCD. Unlike women who had VCD, those who underwent VBD were more likely to have
      prolonged labour (OR 8.05; 95% CI 3.00 to 11.47; P<0.001), and their newborns
      were more likely to suffer from birth asphyxia (OR 10.24; 95% CI 4.92 to 21.31;
      P<0.001). CONCLUSION: The study infers a strong association between VBD of
      singleton term pregnancies and maternofetal morbidity when specific protocols are
      applied. This, however, failed to translate into higher differences in perinatal
      mortality. This finding does not discount the role of VBD in low-income
      countries, but we emphasise the need for specific precautions like close
      monitoring of labour and adequate anticipation for neonatal resuscitation in
      order to reduce these complications.

PMID- 29170288
TI  - Midwife or doctor local opinion leader to implement a national guideline in
      babies on postnatal wards (DesIGN): protocol of a cluster-randomised, blinded,
      controlled trial.
AB  - INTRODUCTION: Neonatal hypoglycaemia is a common condition that can cause
      developmental delay. Treatment of neonatal hypoglycaemia with oral dextrose gel
      has been shown to reverse hypoglycaemia and reduce admissions to neonatal
      intensive care for hypoglycaemia. An evidence-based clinical practice guideline
      was written to guide the use of dextrose gel to treat neonatal hypoglycaemia in
      New Zealand. However, it is unclear what clinical discipline might most
      effectively lead the implementation of the guideline recommendations. OBJECTIVE:
      To determine if midwife or doctor local opinion leaders are more effective in
      implementing a clinical practice guideline for use of oral dextrose gel to treat
      hypoglycaemia in babies on postnatal wards. METHODS AND ANALYSIS: A cluster
      randomised, blinded, controlled trial. New Zealand maternity hospitals that care
      for babies born at risk of neonatal hypoglycaemia will be randomised to having
      either a local midwife or doctor lead the guideline implementation at that
      hospital. The primary outcome will be the change in the proportion of
      hypoglycaemic babies treated with dextrose gel from before implementation of the
      guideline to 3 months after implementation. ETHICS AND DISSEMINATION: Approved by
      Health and Disability Ethics Committee: 15/NTA/31. Findings will be disseminated
      to peer-reviewed journals, guideline developers and the public. TRIAL
      REGISTRATION NUMBER: ISRCTN61154098.

PMID- 29170289
TI  - Use of driving-impairing medicines by a Spanish population: a population-based
      registry study.
AB  - OBJECTIVE: To assess the use of driving-impairing medicines (DIM) in the general
      population with special reference to length of use and concomitant use. DESIGN:
      Population-based registry study. SETTING: The year 2015 granted medicines
      consumption data recorded in the Castile and Leon (Spain) medicine dispensation
      registry was consulted. PARTICIPANTS: Medicines and DIM consumers from a Spanish
      population (Castile and Leon: 2.4 million inhabitants). EXPOSURE: Medicines and
      DIM consumption. Patterns of use by age and gender based on the length of use
      (acute: 1-7 days, subacute: 8-29 days and chronic use: >=30 days) were of
      interest. Estimations regarding the distribution of licensed drivers by age and
      gender were employed to determine the patterns of use of DIM. RESULTS: DIM were
      consumed by 34.4% (95% CI 34.3% to 34.5%) of the general population in 2015, more
      commonly with regularity (chronic use: 22.5% vs acute use: 5.3%) and more
      frequently by the elderly. On average, 2.3 DIM per person were dispensed,
      particularly to chronic users (2.8 DIM per person). Age and gender distribution
      differences were observed between the Castile and Leon medicine dispensation
      registry data and the drivers' license census data. Of all DIM dispensed, 83.8%
      were in the Anatomical Therapeutic Chemical code group nervous system medicines
      (N), which were prescribed to 29.2% of the population. CONCLUSIONS: The use of
      DIM was frequent in the general population. Chronic use was common, but acute and
      subacute use should also be considered. This finding highlights the need to make
      patients, health professionals, health providers, medicine regulatory agencies
      and policy-makers at large aware of the role DIM play in traffic safety.

PMID- 29170290
TI  - Cerebrospinal fluid biomarkers for the diagnosis and prognosis of Parkinson's
      disease: protocol for a systematic review and individual participant data meta
      analysis.
AB  - INTRODUCTION: Idiopathic Parkinson's disease (PD) is a progressive
      neurodegenerative disorder related to alpha-synuclein misfolding and aggregation.
      For this reason, it belongs to the family of 'synucleinopathies', which also
      includes some other neurological diseases. Although imaging and ancillary
      investigations may be helpful in the diagnostic workup, the diagnosis of PD
      mostly relies on the clinician's expertise. Furthermore, there is a need today
      for markers that can track the disease progression in PD that might improve the
      evaluation of novel disease-modifying therapies. The cerebrospinal fluid (CSF)
      has been widely investigated with the purpose of finding useful diagnostic and
      prognostic biomarkers for PD. METHODS AND ANALYSIS: This systematic review
      protocol has been developed according to the Preferred Reporting Items for
      Systematic reviews and Meta-Analyses Protocol 2015 statement and was registered
      on the PROSPERO international prospective register of systematic reviews. An
      international collaboration will be established. We will search the Cochrane
      Library, Web of Science, Medline and Embase from inception, using appropriate
      search strategies. Individual participant data from all included studies will be
      merged into a single database. We will include any study assessing the diagnostic
      and prognostic role of CSF biomarkers in PD. To evaluate the risk of bias and
      applicability of primary diagnostic accuracy studies, we will use Quality
      Assessment of Diagnostic Accuracy Studies-2 and Quality in Prognostic Studies. We
      will use standard meta-analytic procedures. We will first explore the utility of
      each CSF biomarker in turn. For each biomarker, we will assess its diagnostic and
      prognostic utility by means of receiver operating characteristic analysis and
      regression models. We will then move towards a multivariate approach considering
      different panels of biomarkers. ETHICS AND DISSEMINATION: Our study will not
      include confidential data, and no intervention will be involved, so ethical
      approval is not required. The results of the study will be reported in
      international peer-reviewed journals.

PMID- 29170291
TI  - Authorship, plagiarism and conflict of interest: views and practices from
      low/middle-income country health researchers.
AB  - OBJECTIVES: To document low/middle-income country (LMIC) health researchers'
      views about authorship, redundant publication, plagiarism and conflicts of
      interest and how common poor practice was in their institutions. DESIGN: We
      developed a questionnaire based on scenarios about authorship, redundant
      publication, plagiarism and conflicts of interest. We asked participants whether
      the described practices were acceptable and whether these behaviours were common
      at their institutions. We conducted in-depth interviews with respondents who
      agreed to be interviewed. PARTICIPANTS: We invited 607 corresponding authors of
      Cochrane reviews working in LMICs. From the 583 emails delivered, we obtained 199
      responses (34%). We carried out in-depth interviews with 15 respondents. RESULTS:
      Seventy-seven per cent reported that guest authorship occurred at their
      institution, 60% reported text recycling. For plagiarism, 12% of respondents
      reported that this occurred 'occasionally', and 24% 'rarely'. Forty per cent
      indicated that their colleagues had not declared conflicts of interest in the
      past. Respondents generally recognised poor practice in scenarios but reported
      that they occurred at their institutions. Themes identified from in-depth
      interviews were (1) authorship rules are simple in theory, but not consistently
      applied; (2) academic status and power underpin behaviours; (3) institutions and
      culture fuel bad practices and (4) researchers are uncertain about what conflict
      of interests means and how this may influence research. CONCLUSIONS: LMIC
      researchers report that guest authorship is widely accepted and common. While
      respondents report that plagiarism and undeclared conflicts of interest are
      unacceptable in practice, they appear common. Determinants of poor practice
      relate to academic status and power, fuelled by institutional norms and culture.

PMID- 29170292
TI  - Core outcome research measures in anal cancer (CORMAC): protocol for systematic
      review, qualitative interviews and Delphi survey to develop a core outcome set in
      anal cancer.
AB  - INTRODUCTION: The incidence of anal squamous cell carcinoma (ASCC) has increased
      threefold in the last 30 years. Initial treatment is chemoradiotherapy,
      associated with short-term and long-term side effects. Future therapy innovations
      aim to reduce morbidity in treatment of early tumours while maintaining treatment
      efficacy, and to escalate treatment intensity in locally advanced tumours with
      acceptable quality of life (QoL). However, all phase III randomised controlled
      trials to-date have utilised different primary outcomes, which hinders evidence
      synthesis and presents challenges to the selection of optimal outcomes in future
      trials. No trial comprehensively assessed long-term side effects and QoL,
      suggesting outcomes reflecting issues important to patients are under
      represented. This project aims to determine the priority outcomes for all
      stakeholders and reach agreement on a standardised core set of outcomes to be
      measured and reported on in all future ASCC trials. METHODS AND ANALYSIS: A
      systematic review will identify all outcomes reported in trials and observational
      studies of chemoradiotherapy as primary treatment for ASCC. Outcomes of
      importance to patients will be identified through patient interviews. The long
      list of outcomes generated from the systematic review and interviews will be used
      to create a two-round Delphi process, including key stakeholders (patients and
      healthcare professionals). The results of the Delphi will be discussed at a face
      to-face consensus meeting. Discussion will focus on outcomes that did not achieve
      consensus through the Delphi process and conclude with anonymous voting to ratify
      the final core outcome set (COS). ETHICS AND DISSEMINATION: The final COS will
      feed directly into the PersonaLising Anal cancer radioTherapy dOse (PLATO)
      national anal cancer trials and the Association of coloproctologists of Great
      Britain and Ireland (ACPGBI) supported national anal cancer database. Utilisation
      of the COS will increase the relevance of research output to all stakeholders and
      increase the capacity for data synthesis between trials. This study has ethical
      approval and is registered with the Core Outcome Measures in Effectiveness Trials
      (COMET) initiative. TRIAL REGISTRATION NUMBER: PROSPERO registration ID:
      CRD42016036540.

PMID- 29170293
TI  - Identifying clinical features in primary care electronic health record studies:
      methods for codelist development.
AB  - OBJECTIVE: Analysis of routinely collected electronic health record (EHR) data
      from primary care is reliant on the creation of codelists to define clinical
      features of interest. To improve scientific rigour, transparency and
      replicability, we describe and demonstrate a standardised reproducible
      methodology for clinical codelist development. DESIGN: We describe a three-stage
      process for developing clinical codelists. First, the clear definition a priori
      of the clinical feature of interest using reliable clinical resources. Second,
      development of a list of potential codes using statistical software to
      comprehensively search all available codes. Third, a modified Delphi process to
      reach consensus between primary care practitioners on the most relevant codes,
      including the generation of an 'uncertainty' variable to allow sensitivity
      analysis. SETTING: These methods are illustrated by developing a codelist for
      shortness of breath in a primary care EHR sample, including modifiable syntax for
      commonly used statistical software. PARTICIPANTS: The codelist was used to
      estimate the frequency of shortness of breath in a cohort of 28 216 patients aged
      over 18 years who received an incident diagnosis of lung cancer between 1 January
      2000 and 30 November 2016 in the Clinical Practice Research Datalink (CPRD).
      RESULTS: Of 78 candidate codes, 29 were excluded as inappropriate. Complete
      agreement was reached for 44 (90%) of the remaining codes, with partial
      disagreement over 5 (10%). 13 091 episodes of shortness of breath were identified
      in the cohort of 28 216 patients. Sensitivity analysis demonstrates that codes
      with the greatest uncertainty tend to be rarely used in clinical practice.
      CONCLUSIONS: Although initially time consuming, using a rigorous and reproducible
      method for codelist generation 'future-proofs' findings and an auditable,
      modifiable syntax for codelist generation enables sharing and replication of EHR
      studies. Published codelists should be badged by quality and report the methods
      of codelist generation including: definitions and justifications associated with
      each codelist; the syntax or search method; the number of candidate codes
      identified; and the categorisation of codes after Delphi review.

PMID- 29170294
TI  - De Winter's wave.

PMID- 29170295
TI  - BET 1: Can the Manchester Acute Coronary Syndromes and Troponin-only Manchester
      Acute Coronary Syndromes decision aids rule out acute coronary syndromes in the
      emergency department?
AB  - A short-cut review was carried out to establish whether the Manchester Acute
      Coronary Syndromes (MACS) and Troponin-only MACS (T-MACS) decision aids can
      safely rule out acute coronary syndromes in patients presenting to the ED with
      suspected cardiac chest pain. Six studies were directly relevant to the question.
      The author, date and country of publication, patient group studied, study type,
      relevant outcomes, results and study weaknesses of these papers are tabulated.
      The clinical bottom line is that both rules have high sensitivity for acute
      coronary syndromes, including the detection of major adverse cardiac events at 30
      days. The original MACS algorithm may have marginally greater sensitivity than T
      MACS but has inferior specificity and requires the use of a biomarker assay (for
      heart-type fatty acid binding protein) that is not currently widely used in
      practice.

PMID- 29170297
TI  - BET 2: Sharing decisions for patients with suspected cardiac chest pain in the
      emergency department.
AB  - A short-cut review was carried out to establish whether shared decision making
      used alongside a decision aid can lead to greater patient satisfaction, lower
      healthcare resource use and non-inferior clinical outcomes in patients with
      suspected acute coronary syndromes. Four studies were directly relevant to the
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these papers are
      tabulated. The clinical bottom line is that the use of shared decision-making
      tools in the ED for management of patients with low-risk chest pain appears to be
      beneficial to the patient and the physician. Use of these shared decision-making
      tools appears to increase patient knowledge and satisfaction, while decreasing
      decision conflict and resource use, without causing additional negative outcomes
      for the patient.

PMID- 29170318
TI  - 21 Daily dynamic discharge - a whole system solution to ED crowding.
AB  - INTRODUCTION: ED crowding is associated with increased mortality, poor staff and
      patient experience, an increased inpatient length of stay and poor compliance
      with the four-hour emergency access standard.1 Where crowding is caused by exit
      block, the focus needs to be on whole system patient management, reducing the
      temporal mismatch between admissions and discharges since at times of peak demand
      hospitals may become gridlocked until patients are discharged.In an attempt to
      tackle exit block, the Scottish Government Unscheduled Care Team have implemented
      the Daily Dynamic Discharge (DDD) approach, which aims to increase the number of
      inpatient discharges by 12 pm, thus enabling more timeous flow through the ED.
      METHODS: A series of meetings were held between the Unscheduled Care Team and the
      clinical and managerial staff of Dumfries and Galloway Royal Infirmary over a two
      week period to train staff on implementing the elements of the Daily Dynamic
      Discharge approach. These included holding a daily whiteboard meeting with input
      from the multidisciplinary team, early determination of an Estimated Date of
      Discharge (EDD) for each patient, and conducting 'golden hour' ward rounds
      whereby the highest acuity patients were seen first followed by those who were
      expected to be discharged that day, thus increasing the number of discharges by
      12 pm. RESULTS: Over a twelve-week period the average number of weekly discharges
      increased from 26.5 to 30.2, i.e., an average increase of 3.7 discharges per
      week. Average length of stay dropped from 6.8 days to 6.2 days, a saving of 0.6
      days.The median discharge time was 32 min earlier once DDD had been implemented.
      Previously, a third (33%) of patients were discharged before 4 pm; after
      implementation, this rose to 44%. DISCUSSION: Emergency Department activity, and
      particularly crowding, is the barometer for the rest of the hospital, and the
      only way to guarantee that patients who require admission, get into the right
      bed, and in a timely way, is to ensure that the downstream wards discharge
      sufficient numbers early in the day to accommodate admissions from the ED.The DDD
      approach has been shown to be effective in increasing the number of discharges by
      12 pm, smoothing the admission/discharge profile, and is now being adopted in
      other hospitals throughout Scotland. REFERENCE: Richardson DB. Increase in
      patient mortality at 10 days associated with emergency department overcrowding.
      Med J Aust2006;184(5):213-216.

PMID- 29170355
TI  - A teenage girl with lower abdominal pain.

PMID- 29170356
TI  - Multidisciplinary team approach to heart failure management.

PMID- 29170357
TI  - Role of cardiovascular magnetic resonance in the management of patients with
      stable coronary artery disease.
AB  - Cardiovascular magnetic resonance (CMR) assesses cardiac function, ischaemia,
      viability and tissue characterisation, all within a single scan. Many studies
      regarding the role of CMR in stable coronary artery disease (CAD) have been
      published over the last decade providing important technical advances, large
      scale clinical validation and prognostic data. As a result, CMR has emerged as a
      highly accurate technique for diagnosis and risk stratification in stable CAD and
      has been incorporated into national and international guidelines. Furthermore,
      clinical pathways utilising CMR have been shown to be the most cost-effective in
      several healthcare systems. In this review, we summarise the key roles and
      guideline recommendations for CMR in stable CAD supported by contemporary
      clinical evidence.

PMID- 29170358
TI  - Cardiopulmonary fitness in children with congenital heart diseases versus healthy
      children.
AB  - OBJECTIVE: We aimed to compare the cardiopulmonary fitness of children with
      congenital heart diseases (CHD) with that of age-adjusted and gender-adjusted
      controls. We also intended to identify clinical characteristics associated with
      maximum oxygen uptake (VO2max) in this population. METHODS AND RESULTS: We
      included in a cross-sectional multicentre study a total of 798 children (496 CHD
      and 302 controls) who underwent a complete cardiopulmonary exercise test (CPET).
      The association of clinical characteristics with VO2max was studied using a
      multivariate analysis. Mean VO2max in the CHD group and control represented 93%+/
      20% and 107%+/-17% of predicted values, respectively. VO2max was significantly
      lower in the CHD group, overall (37.8+/-0.3vs 42.6+/-0.4 mL/kg/min, P<0.0001) and
      for each group (P<0.05). The mean VO2max decline per year was significantly
      higher in CHD than in the controls overall (-0.84+/-0.10 vs -0.19+/-0.14
      mL/kg/min/year, P<0.01), for boys (-0.72+/-0.14vs 0.11+/-0.19 mL/kg/min/year,
      P<0.01) and for girls (-1.00+/-0.13 vs -0.55+/-0.21 mL/kg/min/year, P=0.05).
      VO2max was associated with body mass index, ventilatory anaerobic threshold,
      female gender, restrictive ventilatory disorder, right ventricle systolic
      hypertension, tricuspid regurgitation, the number of cardiac catheter or surgery
      procedures, and the presence of a genetic anomaly. CONCLUSIONS: Although the
      magnitude of the difference was not large, VO2max among children with CHD was
      significantly lower than in normal children. We suggest performing CPET in
      routine follow-up of these patients. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov NCT01202916;Post-results.

PMID- 29170359
TI  - Non-antibiotic options for recurrent urinary tract infections in women.

PMID- 29170360
TI  - Sex-specific cardiovascular susceptibility to ischaemic myocardial injury
      following exposure to prenatal hypoxia.
AB  - Cardiovascular diseases (CVDs) are the leading cause of mortality and
      hypertension contributes substantially to the incidence of stroke, coronary
      artery disease, heart failure, atrial fibrillation and peripheral vascular
      disease. The origin of hypertension is clearly multifactorial, and a complex and
      multifaceted approach is necessary to decrease its incidence. The most
      recognizable factors involved in reducing the incidence of hypertension are
      prevention, early diagnosis and treatment; however, the importance of the foetal
      environment and early postnatal development has recently been considered. In
      clinical practice, these factors are still frequently overlooked, probably
      because of a lack of knowledge about the underlying mechanisms and effective
      treatment or prevention. Pathophysiological mechanisms underlying the prenatal
      programming of CVDs were investigated in the study by Shah et al. published
      recently in Clinical Science (2017) 131(17), 2303-2317. The study explored
      cardiac susceptibility of adult male and female rat offspring to ischaemic
      myocardial injury due to prenatal exposure to hypoxia. The results demonstrated
      significant changes in global cardiac function and left ventricular dilatation
      following myocardial infarction in rat offspring prenatally exposed to hypoxia.
      The effects were gender specific and occurred only in males, whereas females were
      protected. These findings are important from several perspectives. First, they
      point to the fact that an inadequate foetal environment can increase
      susceptibility to death from myocardial infarction. Second, during their
      reproductive life, females are better protected from cardiovascular insult than
      males, but it is not known if they lose this advantage after menopause, and can
      be equally at risk as males.

PMID- 29170361
TI  - Polycystic ovary syndrome: a common reproductive syndrome with long-term
      metabolic consequences.
AB  - Polycystic ovary syndrome is the most common endocrine disorder among women of
      reproductive age. Although traditionally viewed as a reproductive disorder, there
      is increasing appreciation that it is associated with significantly increased
      risk of cardiometabolic disorders. Women with polycystic ovary syndrome may
      present to clinicians via a variety of different routes and symptoms. Although
      the impact on reproduction predominates during the reproductive years, the
      increased cardiometabolic problems are likely to become more important at later
      stages of the life course. Women with polycystic ovary syndrome have an
      approximately 2- to 5-fold increased risk of dysglycaemia or type 2 diabetes, and
      hence regular screening with oral glucose tolerance test is warranted. Although
      the diagnostic criteria for polycystic ovary syndrome are still evolving and are
      undergoing revision, the diagnosis is increasingly focused on the presence of
      hyperandrogenism, with the significance of polycystic ovarian morphology in the
      absence of associated hyperandrogenism or anovulation remaining uncertain. The
      management of women with polycystic ovary syndrome should focus on the specific
      needs of the individual, and may change according to different stages of the life
      course. In view of the clinical manifestations of the condition, there is recent
      debate about whether the current name is misleading, and whether the condition
      should be renamed as metabolic reproductive syndrome.

PMID- 29170362
TI  - The effect of body mass index on chest trauma severity and prognosis.
AB  - AIM: Patients with thoracic trauma constitute one third of all the trauma cases,
      in west Sicily were recorded 941 thoracic trauma during the period between 2006
      and 2009. Sicily is one of the Italian regions with the highest rate of obesity:
      some studies have demonstrated that obesity is an independent risk factor for
      mortality in high energy blunt traumas. MATERIAL OF STUDY: This study was
      conducted with trauma patients older than 20 years old who presented to our
      Department during the last five years. We only included thoracic injuries and
      politrauma with a thoracic involvement and a BMI >25. Patients were divided into
      two groups: HET and LET patients. RESULTS: Thoracic trauma was more common in
      patients with a BMI >25 than in normo-weight and clinic admission rate, length of
      hospital stay and ISS score increased in proportion with the increase of BMI.
      Both HET (high energy trauma) and LET (low energy trauma) revealed that
      overweight, obese and morbidly obese patients had greater admissions and length
      of hospital stay. DISCUSSION: The overweight and obese population has increased
      substantially over the last two decades and 61,5% of the Sicilian population is
      above normal weight. A large body mass with excess adiposity may contribute to
      HET injuries in several ways. Obesity has a number of comorbidities that reduce
      chances of recovery in overweight and obese patients experienced thoracic trauma
      both HET and LET. CONCLUSION: Obesity increases morbidity independently of injury
      severity in thoracic trauma patients. As BMI increased, length of hospital stay
      increased and prognosis deteriorates. KEY WORDS: BMI, Obesity, Thoracic trauma.

PMID- 29170363
TI  - The Influence of Class II Division 2 Malocclusions on the Harmony of the Human
      Face Profile.
AB  - BACKGROUND Persons with class II division 2 malocclusion are characterized by a
      very specific dento-skeletal and soft-tissue profile (a profile in which a
      protruding nose and chin, retruding lips, concave and shortened lower third of
      the face, and gummy smile are dominant), which is the opposite of the currently
      modern profiles (convex profile of protruding lips and small chin). The aim of
      this research was to determine the differences in parameters of harmonies of
      facial profiles between persons with class II division 2 malocclusions and class
      I, and to establish the significance of those differences. MATERIAL AND METHODS
      For this study, 50 patients with class II division 2 malocclusions and 50
      patients with class I were selected; profile photos were recorded and a
      photometric analysis was done: a type of profile according to Schwarz, the shape
      of a nose, the prominence of chin, biometrical field, the position of lips in
      relation to the tangent Sn-Pg, S-line (Steiner), E-line (Riketts) and a facial
      angle according to Arnett. RESULTS The significant differences in profiles of
      persons with class II division 2 compared to class I were: position and
      prominence of the chin, the position of the lower and upper lip in relation to
      the S-line, and smaller value of a facial angle in relation to persons with class
      I. CONCLUSIONS The differences seen in skeletal profiles were not associated with
      significant differences in the profiled facial contours of the examined groups.
      The compensatory role of the fullness of soft tissues of the lips is probably the
      reason why there were not significant deviations in all the examined parameters.

PMID- 29170364
TI  - Acute Fibrinous and Organizing Pneumonia: A Case Report and Review of the
      Literature.
AB  - BACKGROUND Acute fibrinous organizing pneumonia (AFOP) is a rare condition of the
      lung that is associated with acute lung injury, and has a poor prognosis. AFOP is
      characterized histologically by intra-alveolar fibrin. AFOP has been described to
      be associated with lung infections, connective tissue disorders, drugs, toxic
      environmental exposure, and in lung transplantation. However, most cases of AFOP
      remain idiopathic, and because the condition can present with a wide variety of
      clinical manifestations, open lung biopsy or video-assisted thoracoscopic (VAT)
      lung biopsy is necessary for the diagnosis. Currently, treatments for AFOP remain
      under investigation. CASE REPORT A 35-year-old woman presented with a cough and
      dyspnea, and was initially diagnosed to have pneumonia.  Due to the progression
      of her symptoms and increasing respiratory failure she underwent video-assisted
      thoracoscopic (VAT) biopsy and was diagnosed with AFOP, 19 days following
      hospital admission. She was treated with mechanical ventilation, intravenous
      steroids, and cyclophosphamide. She required tracheostomy after 14 days of
      mechanical ventilation and died two weeks later. CONCLUSIONS AFOP is an uncommon
      clinical condition, with a poor prognosis, which often has a delay in diagnosis.
      Some patients benefit from steroids and immunosuppressive therapy. Currently, new
      treatments for AFOP are under investigation.

PMID- 29170365
TI  - Intrahepatic MicroRNA Profile of Liver Transplant Recipients with Hepatitis C
      Virus Co-Infected with Human Immunodeficiency Virus.
AB  - BACKGROUND In patients with human immunodeficiency virus (HIV) and hepatitis C
      virus (HCV) co-infection, HIV can modulate HCV replication and immune response as
      well as accelerate liver fibrosis. The role of miRNA in HIV/HCV co-infection is
      not fully elucidated. The aim of this study was to examine the differential
      expression of miRNAs in the liver. MATERIAL AND METHODS Thirteen patients who had
      undergone a liver transplant (7 HCV-infected and 6 HIV/HCV-co-infected patients)
      were examined using a miRNA array containing 1347 human miRNAs. To confirm the
      microarray results, data for 20 patients (10 HCV-infected and 10 HIV/HCV-co
      infected) were validated using real-time polymerase chain reaction probing for
      miR101b, miR149, and miR200c. This miRNA was selected based on microarray results
      and its biological significance in liver fibrosis. RESULTS Microarray analysis
      revealed 22 miRNAs that were differentially expressed in the HIV/HCV-co-infected
      group compared to the HCV-infected group (p<0.05). The expression of miR-101b and
      miR149 was significantly decreased in the HIV/HCV-co-infected group compared to
      that in the HCV-infected group (miR101b, 0.103+/-0.09 vs. 0.0157+/-0.0093,
      p=0.007; miR149, 0.152+/-0.159 vs. 0.0192+/-0.015, p=0.025). CONCLUSIONS HIV/HCV
      co-infection may promote liver fibrosis by modulating miRNA expression.

PMID- 29170367
TI  - Simulating quantum light propagation through atomic ensembles using matrix
      product states.
AB  - A powerful method to interface quantum light with matter is to propagate the
      light through an ensemble of atoms. Recently, a number of such interfaces have
      emerged, most prominently Rydberg ensembles, that enable strong nonlinear
      interactions between propagating photons. A largely open problem is whether these
      systems produce exotic many-body states of light and developing new tools to
      study propagation in the large photon number limit is highly desirable. Here we
      provide a method based on a "spin model" that maps quasi one-dimensional (1D)
      light propagation to the dynamics of an open 1D interacting spin system, where
      all photon correlations are obtained from those of the spins. The spin dynamics
      in turn are numerically solved using the toolbox of matrix product states. We
      apply this formalism to investigate vacuum induced transparency, wherein the
      different photon number components of a pulse propagate with number-dependent
      group velocity and separate at output.

PMID- 29170368
TI  - Author Correction: Demonstration of sub-luminal propagation of single-cycle
      terahertz pulses for particle acceleration.
AB  - The original version of this Article contained an error in the abstract,
      referring to "multi-megawatt-per-metre" instead of "multi-megavolt-per-metre".
      This has now been corrected in both the PDF and HTML versions of the Article.

PMID- 29170366
TI  - Initiation of HIV neutralizing B cell lineages with sequential envelope
      immunizations.
AB  - A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of
      broadly neutralizing antibodies (bnAbs) in infection and to recreate those events
      by vaccination. Here, we report host tolerance mechanisms that limit the
      development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1
      Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1
      strains, recognize open Env trimers, and accumulate relatively modest somatic
      mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env+B cell
      clones develop anergy and partial deletion at the transitional to mature B cell
      stage, but become Env- upon receptor editing. In comparison with repetitive Env
      immunizations, sequential Env administration rescue anergic Env+ (non-edited)
      precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses,
      but immune tolerance mechanisms restrict their development, suggesting that
      sequential immunogen-based vaccine regimens will likely need to incorporate
      strategies to expand bnAb precursor pools.

PMID- 29170371
TI  - Multicomponent mapping of boron chemotypes furnishes selective enzyme inhibitors.
AB  - Heteroatom-rich organoboron compounds have attracted attention as modulators of
      enzyme function. Driven by the unmet need to develop chemoselective access to
      boron chemotypes, we report herein the synthesis of alpha- and beta
      aminocyano(MIDA)boronates from borylated carbonyl compounds. Activity-based
      protein profiling of the resulting beta-aminoboronic acids furnishes selective
      and cell-active inhibitors of the (ox)lipid-metabolizing enzyme alpha/beta
      hydrolase domain 3 (ABHD3). The most potent compound displays nanomolar in vitro
      and in situ IC50 values and fully inhibits ABHD3 activity in human cells with no
      detectable cross-reactivity against other serine hydrolases. These findings
      demonstrate that synthetic methods that enhance the heteroatom diversity of boron
      containing molecules within a limited set of scaffolds accelerate the discovery
      of chemical probes of human enzymes.

PMID- 29170369
TI  - Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function.
AB  - The co-chaperone FKBP5 is a stress-responsive protein-regulating stress
      reactivity, and its genetic variants are associated with T2D related traits and
      other stress-related disorders. Here we show that FKBP51 plays a role in energy
      and glucose homeostasis. Fkbp5 knockout (51KO) mice are protected from high-fat
      diet-induced weight gain, show improved glucose tolerance and increased insulin
      signaling in skeletal muscle. Chronic treatment with a novel FKBP51 antagonist,
      SAFit2, recapitulates the effects of FKBP51 deletion on both body weight
      regulation and glucose tolerance. Using shorter SAFit2 treatment, we show that
      glucose tolerance improvement precedes the reduction in body weight.
      Mechanistically, we identify a novel association between FKBP51 and AS160, a
      substrate of AKT2 that is involved in glucose uptake. FKBP51 antagonism increases
      the phosphorylation of AS160, increases glucose transporter 4 expression at the
      plasma membrane, and ultimately enhances glucose uptake in skeletal myotubes. We
      propose FKBP51 as a mediator between stress and T2D development, and potential
      target for therapeutic approaches.

PMID- 29170370
TI  - Receptor-binding loops in alphacoronavirus adaptation and evolution.
AB  - RNA viruses are characterized by a high mutation rate, a buffer against
      environmental change. Nevertheless, the means by which random mutation improves
      viral fitness is not well characterized. Here we report the X-ray crystal
      structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV
      229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN).
      Three extended loops are solely responsible for receptor binding and the
      evolution of HCoV-229E and its close relatives is accompanied by changing loop
      receptor interactions. Phylogenetic analysis shows that the natural HCoV-229E
      receptor-binding loop variation observed defines six RBD classes whose viruses
      have successively replaced each other in the human population over the past 50
      years. These RBD classes differ in their affinity for APN and their ability to
      bind an HCoV-229E neutralizing antibody. Together, our results provide a model
      for alphacoronavirus adaptation and evolution based on the use of extended loops
      for receptor binding.

PMID- 29170372
TI  - High magnesium mobility in ternary spinel chalcogenides.
AB  - Magnesium batteries appear a viable alternative to overcome the safety and energy
      density limitations faced by current lithium-ion technology. The development of a
      competitive magnesium battery is plagued by the existing notion of poor magnesium
      mobility in solids. Here we demonstrate by using ab initio calculations, nuclear
      magnetic resonance, and impedance spectroscopy measurements that substantial
      magnesium ion mobility can indeed be achieved in close-packed frameworks (~ 0.01
      0.1 mS cm-1 at 298 K), specifically in the magnesium scandium selenide spinel.
      Our theoretical predictions also indicate that high magnesium ion mobility is
      possible in other chalcogenide spinels, opening the door for the realization of
      other magnesium solid ionic conductors and the eventual development of an all
      solid-state magnesium battery.

PMID- 29170373
TI  - Caldera resurgence driven by magma viscosity contrasts.
AB  - Calderas are impressive volcanic depressions commonly produced by major
      eruptions. Equally impressive is the uplift of the caldera floor that may follow,
      dubbed caldera resurgence, resulting from magma accumulation and accompanied by
      minor eruptions. Why magma accumulates, driving resurgence instead of feeding
      large eruptions, is one of the least understood processes in volcanology. Here we
      use thermal and experimental models to define the conditions promoting
      resurgence. Thermal modelling suggests that a magma reservoir develops a growing
      transition zone with relatively low viscosity contrast with respect to any newly
      injected magma. Experiments show that this viscosity contrast provides a
      rheological barrier, impeding the propagation through dikes of the new injected
      magma, which stagnates and promotes resurgence. In explaining resurgence and its
      related features, we provide the theoretical background to account for the
      transition from magma eruption to accumulation, which is essential not only to
      develop resurgence, but also large magma reservoirs.

PMID- 29170375
TI  - Reconciling grain growth and shear-coupled grain boundary migration.
AB  - Conventional models for grain growth are based on the assumption that grain
      boundary (GB) velocity is proportional to GB mean curvature. We demonstrate via a
      series of molecular dynamics (MD) simulations that such a model is inadequate and
      that many physical phenomena occur during grain boundary migration for which this
      simple model is silent. We present a series of MD simulations designed to unravel
      GB migration phenomena and set it in a GB migration context that accounts for
      competing migration mechanisms, elasticity, temperature, and grain boundary
      crystallography. The resultant formulation is quantitative and validated through
      a series of atomistic simulations. The implications of this model for
      microstructural evolution is described. We show that consideration of GB
      migration mechanisms invites considerable complexity even under ideal conditions.
      However, that complexity also grants these systems enormous flexibility, and that
      flexibility is key to the decades-long success of conventional grain growth
      theories.

PMID- 29170374
TI  - R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of
      regenerating vasculature.
AB  - The formation of endothelial lumen is fundamental to angiogenesis and essential
      to the oxygenation of hypoxic tissues. The molecular mechanism underlying this
      important process remains obscure. Here, we show that Akt activation by a Ras
      homolog, R-Ras, stabilizes the microtubule cytoskeleton in endothelial cells
      leading to endothelial lumenogenesis. The activation of Akt by the potent
      angiogenic factor VEGF-A does not strongly stabilize microtubules or sufficiently
      promote lumen formation, hence demonstrating a distinct role for the R-Ras-Akt
      axis. We show in mice that this pathway is important for the lumenization of new
      capillaries and microvessels developing in ischemic muscles to allow sufficient
      tissue reperfusion after ischemic injury. Our work identifies a role for Akt in
      lumenogenesis and the significance of the R-Ras-Akt signaling for the patency of
      regenerating blood vessels.

PMID- 29170376
TI  - Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2.
AB  - The target of rapamycin (TOR) kinase assembles into two distinct multiprotein
      complexes, conserved across eukaryote evolution. In contrast to TOR complex 1
      (TORC1), TORC2 kinase activity is not inhibited by the macrolide rapamycin. Here,
      we present the structure of Saccharomyces cerevisiae TORC2 determined by electron
      cryo-microscopy. TORC2 contains six subunits assembling into a 1.4 MDa
      rhombohedron. Tor2 and Lst8 form the common core of both TOR complexes.
      Avo3/Rictor is unique to TORC2, but interacts with the same HEAT repeats of Tor2
      that are engaged by Kog1/Raptor in mammalian TORC1, explaining the mutual
      exclusivity of these two proteins. Density, which we conclude is Avo3, occludes
      the FKBP12-rapamycin-binding site of Tor2's FRB domain rendering TORC2 rapamycin
      insensitive and recessing the kinase active site. Although mobile, Avo1/hSin1
      further restricts access to the active site as its conserved-region-in-the-middle
      (CRIM) domain is positioned along an edge of the TORC2 active-site-cleft,
      consistent with a role for CRIM in substrate recruitment.

PMID- 29170378
TI  - Publisher Correction: Cortical dendritic activity correlates with spindle-rich
      oscillations during sleep in rodents.
AB  - In the originally published version of this Article, incorrect references were
      cited on two occasions in the Results section. Under the subheading 'Ca2+
      activity in single dendrites and somata of L5 neurons', the final sentence of the
      second paragraph incorrectly cited reference 29 instead of reference 31. Under
      the subheading 'Spiking of L5 cell bodies is not influenced by spindles', the
      first sentence cited reference 30 instead of reference 29. These errors have now
      been corrected in both the PDF and HTML versions of the Article.

PMID- 29170377
TI  - Transformation of the head-direction signal into a spatial code.
AB  - Animals integrate multiple sensory inputs to successfully navigate in their
      environments. Head direction (HD), boundary vector, grid and place cells in the
      entorhinal-hippocampal network form the brain's navigational system that allows
      to identify the animal's current location, but how the functions of these
      specialized neuron types are acquired remain to be understood. Here we report
      that activity of HD neurons is influenced by the ambulatory constraints imposed
      upon the animal by the boundaries of the explored environment, leading to
      spurious spatial information. However, in the post-subiculum, the main cortical
      stage of HD signal processing, HD neurons convey true spatial information in the
      form of border modulated activity through the integration of additional sensory
      modalities relative to egocentric position, unlike their driving thalamic inputs.
      These findings demonstrate how the combination of HD and egocentric information
      can be transduced into a spatial code.

PMID- 29170379
TI  - The influence of the solid to plasma phase transition on the generation of plasma
      instabilities.
AB  - The study of plasma instabilities is a research topic with fundamental importance
      since for the majority of plasma applications they are unwanted and there is
      always the need for their suppression. The initiating physical processes that
      seed the generation of plasma instabilities are not well understood in all plasma
      geometries and initial states of matter. For most plasma instability studies,
      using linear or even nonlinear magnetohydrodynamics (MHD) theory, the most
      crucial step is to correctly choose the initial perturbations imposed either by a
      predefined perturbation, usually sinusoidal, or by randomly seed perturbations as
      initial conditions. Here, we demonstrate that the efficient study of the seeding
      mechanisms of plasma instabilities requires the incorporation of the intrinsic
      real physical characteristics of the solid target in an electro-thermo-mechanical
      multiphysics study. The present proof-of-principle study offers a perspective to
      the understanding of the seeding physical mechanisms in the generation of plasma
      instabilities.

PMID- 29170380
TI  - Josephson emission with frequency span 1-11 THz from small Bi2Sr2CaCu2O8+delta
      mesa structures.
AB  - Mesa structures made of Bi2Sr2CaCu2O8+delta high-temperature superconductor
      represent stacks of atomic scale intrinsic Josephson junctions. They can be used
      for generation of high-frequency electromagnetic waves. Here we analyze Josephson
      emission from small-but-high mesas (with a small area, but containing many
      stacked junctions). We have found strong evidence for tunable terahertz emission
      with a good efficacy in a record high-frequency span 1-11 THz, approaching the
      theoretical upper limit for this superconductor. Emission maxima correspond to in
      phase cavity modes in the mesas, indicating coherent superradiant nature of the
      emission. We conclude that terahertz emission requires a threshold number of
      junctions N ~ 100. The threshold behavior is not present in the classical
      description of stacked Josephson junctions and suggests importance of laser-like
      cascade amplification of the photon number in the cavity.

PMID- 29170381
TI  - Feature-based learning improves adaptability without compromising precision.
AB  - Learning from reward feedback is essential for survival but can become extremely
      challenging with myriad choice options. Here, we propose that learning reward
      values of individual features can provide a heuristic for estimating reward
      values of choice options in dynamic, multi-dimensional environments. We
      hypothesize that this feature-based learning occurs not just because it can
      reduce dimensionality, but more importantly because it can increase adaptability
      without compromising precision of learning. We experimentally test this
      hypothesis and find that in dynamic environments, human subjects adopt feature
      based learning even when this approach does not reduce dimensionality. Even in
      static, low-dimensional environments, subjects initially adopt feature-based
      learning and gradually switch to learning reward values of individual options,
      depending on how accurately objects' values can be predicted by combining feature
      values. Our computational models reproduce these results and highlight the
      importance of neurons coding feature values for parallel learning of values for
      features and objects.

PMID- 29170382
TI  - Publisher Correction: Selective enhancement of optical nonlinearity in two
      dimensional organic-inorganic lead iodide perovskites.
AB  - In the PDF version of this article, Eq. 5 is missing all elements after the
      equals sign. The correct version of Eq. 5 is given below. The HTML version of the
      paper was correct from the time of publication.[Formula: see text].

PMID- 29170383
TI  - Neural bases of ingroup altruistic motivation in soccer fans.
AB  - Humans have a strong need to belong to social groups and a natural inclination to
      benefit ingroup members. Although the psychological mechanisms behind human
      prosociality have extensively been studied, the specific neural systems bridging
      group belongingness and altruistic motivation remain to be identified. Here, we
      used soccer fandom as an ecological framing of group membership to investigate
      the neural mechanisms underlying ingroup altruistic behaviour in male fans using
      event-related functional magnetic resonance. We designed an effort measure based
      on handgrip strength to assess the motivation to earn money (i) for oneself, (ii)
      for anonymous ingroup fans, or (iii) for a neutral group of anonymous non-fans.
      While overlapping valuation signals in the medial orbitofrontal cortex (mOFC)
      were observed for the three conditions, the subgenual cingulate cortex (SCC)
      exhibited increased functional connectivity with the mOFC as well as stronger
      hemodynamic responses for ingroup versus outgroup decisions. These findings
      indicate a key role for the SCC, a region previously implicated in altruistic
      decisions and group affiliation, in dovetailing altruistic motivations with
      neural valuation systems in real-life ingroup behaviour.

PMID- 29170384
TI  - The origin of motif families in food webs.
AB  - Food webs have been found to exhibit remarkable "motif profiles", patterns in the
      relative prevalences of all possible three-species subgraphs, and this has been
      related to ecosystem properties such as stability and robustness. Analysing 46
      food webs of various kinds, we find that most food webs fall into one of two
      distinct motif families. The separation between the families is well predicted by
      a global measure of hierarchical order in directed networks-trophic coherence. We
      find that trophic coherence is also a good predictor for the extent of omnivory,
      defined as the tendency of species to feed on multiple trophic levels. We compare
      our results to a network assembly model that admits tunable trophic coherence via
      a single free parameter. The model is able to generate food webs in either of the
      two families by varying this parameter, and correctly classifies almost all the
      food webs in our database. This is in contrast with the two most popular food web
      models, the generalized cascade and niche models, which can only generate food
      webs within a single motif family. Our findings suggest the importance of trophic
      coherence in modelling local preying patterns in food webs.

PMID- 29170385
TI  - Temperature dependence of the single photon emission from interface-fluctuation
      GaN quantum dots.
AB  - The temperature dependent single photon emission statistics of interface
      fluctuation GaN quantum dots are reported. Quantum light emission is confirmed at
      temperatures up to ~77 K, by which point the background emission degrades the
      emission purity and results in a measured g(2) (0) in excess of 0.5. A discussion
      on the extent of the background contamination is also given through comparison to
      extensive data taken under various ambient and experimental conditions, revealing
      that the quantum dots themselves are emitting single photons with high purity.

PMID- 29170387
TI  - Microstructural Development in a Laser-Remelted Al-Zn-Si-Mg Coating.
AB  - In the last five decades, there has been intense development in the field of Zn
      Al galvanic coating modification. Recently, Mg was added to improve corrosion
      properties. Further improvements to the coating are possible with additional
      laser surface treatment. In this article, we focus on remelting the Al-Zn-Mg-Si
      layer, using a diode laser with a wide-beam format, concentrating on the
      microstructure development during extreme cooling rates. Laser remelting of the
      Al-Zn-Mg-Si coating and rapid self-quenching produces a finer grain size, and a
      microstructure that is substantially refined and homogenized with respect to the
      phase distribution. Using EBSD results, we are able to understand microstructure
      modification. The laser modified coating has some porosity and intergranular
      cracking which are difficult to avoid, however this does not seem to be
      detrimental to mechanical properties, such as ductility on bending. The newly
      developed technology has a high potential for improved corrosion performance due
      to highly refined microstructure.

PMID- 29170388
TI  - Influence of Stage Cooling Method on Pore Architecture of Biomimetic Alginate
      Scaffolds.
AB  - Porous scaffold is widely used in the field of tissue engineering. However, the
      anisotropic structure of actual extracellular matrix (ECM) of human tissue pose a
      challenge to the scaffold structure that pore size should be changed in gradient.
      Here we report a stage cooling method to fabricate alginate scaffold with
      gradient pores. Eight cooling models were set according to different temperature
      steps, different initial temperature, and different time duration. The thermal
      characterization of solution during cooling process were recorded and scaffold
      morphology were observed. The results revealed that the temperature steps mainly
      affected pore shape, while the initial temperature and time duration mainly
      affected pore size. By altering the initial temperature and time duration,
      scaffold exhibited cellular and gradually enlarged pores on the vertical axial
      direction (10-65 MUm at base, 50-141 MUm at top). With this stage cooling method,
      pore shape and pore size could be easily tailored and scaffold with gradient
      structure could be fabricated.

PMID- 29170386
TI  - Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator
      functions of transcriptional cofactor GRIP1 in macrophages.
AB  - The glucocorticoid (GC) receptor (GR) suppresses inflammation by activating anti
      inflammatory and repressing pro-inflammatory genes. GR-interacting protein-1
      (GRIP1) is a GR corepressor in macrophages, however, whether GRIP1 mediates GR
      activated transcription, and what dictates its coactivator versus corepressor
      properties is unknown. Here we report that GRIP1 loss in macrophages attenuates
      glucocorticoid induction of several anti-inflammatory targets, and that GC
      treatment of quiescent macrophages globally directs GRIP1 toward GR binding sites
      dominated by palindromic GC response elements (GRE), suggesting a non-redundant
      GRIP1 function as a GR coactivator. Interestingly, GRIP1 is phosphorylated at an
      N-terminal serine cluster by cyclin-dependent kinase-9 (CDK9), which is recruited
      into GC-induced GR:GRIP1:CDK9 hetero-complexes, producing distinct GRE-specific
      GRIP1 phospho-isoforms. Phosphorylation potentiates GRIP1 coactivator but,
      remarkably, not its corepressor properties. Consistently, phospho-GRIP1 and CDK9
      are not detected at GR transrepression sites near pro-inflammatory genes. Thus,
      GR restricts actions of its own coregulator via CDK9-mediated phosphorylation to
      a subset of anti-inflammatory genes.

PMID- 29170389
TI  - Ultra-wideband polarization conversion metasurface and its application cases for
      antenna radiation enhancement and scattering suppression.
AB  - A double-layer complementary metasurface (MS) with ultra-wideband polarization
      conversion is presented. Then, we propose two application cases by applying the
      polarization conversion structures to aperture coupling patch antenna (ACPA). Due
      to the existence of air-filled gap of ACPA, air substrate and dielectric
      substrate are used to construct the double-layer MS. The polarization conversion
      bandwidth is broadened toward low-frequency range. Subsequently, two application
      cases of antenna are proposed and investigated. The simultaneous improvement of
      radiation and scattering performance of antenna is normally considered as a
      contradiction. Gratifyingly, the contradiction is addressed in these two
      application cases. According to different mechanism of scattering suppression
      (i.e., polarization conversion and phase cancellation), the polarization
      conversion structures are utilized to construct uniform and orthogonal
      arrangement configurations. And then, the configurations are integrated into ACPA
      and two different kinds of metasurface-based (MS-based) ACPA are formed.
      Radiation properties of the two MS-based ACPAs are improved by optimizing the
      uniform and orthogonal arrangement configurations. The measured results suggest
      that ultra-wideband polarization conversion properties of the MS are achieved and
      radiation enhancement and scattering suppression of the two MS-based ACPAs are
      obtained. These results demonstrate that we provide novel approach to design high
      performance polarization conversion MS and MS-based devices.

PMID- 29170390
TI  - Systems analysis of latent HIV reversal reveals altered stress kinase signaling
      and increased cell death in infected T cells.
AB  - Viral latency remains the most significant obstacle to HIV eradication. Clinical
      strategies aim to purge the latent CD4+ T cell reservoir by activating viral
      expression to induce death, but are undercut by the inability to target latently
      infected cells. Here we explored the acute signaling response of latent HIV
      infected CD4+ T cells to identify dynamic phosphorylation signatures that could
      be targeted for therapy. Stimulation with CD3/CD28, PMA/ionomycin, or latency
      reversing agents prostratin and SAHA, yielded increased phosphorylation of
      IkappaBalpha, ERK, p38, and JNK in HIV-infected cells across two in vitro latency
      models. Both latent infection and viral protein expression contributed to changes
      in perturbation-induced signaling. Data-driven statistical models calculated from
      the phosphorylation signatures successfully classified infected and uninfected
      cells and further identified signals that were functionally important for
      regulating cell death. Specifically, the stress kinase pathways p38 and JNK were
      modified in latently infected cells, and activation of p38 and JNK signaling by
      anisomycin resulted in increased cell death independent of HIV reactivation. Our
      findings suggest that altered phosphorylation signatures in infected T cells
      provide a novel strategy to more selectively target the latent reservoir to
      enhance eradication efforts.

PMID- 29170391
TI  - Preventive effect of Agnucastoside C against Isoproterenol-induced myocardial
      injury.
AB  - An iridoid glycoside, agnucastoside C (ACC) was isolated from the leaves of
      Moringa oliefera and its cardio protective potential was investigated in adult
      rats by examining the effects of this test compound, ACC at 30 mg/kg for 14 days
      in isoproterenol (100 mg/kg)-induced myocardial injury. Isoproterenol (ISO)
      administration induced the myocardial injury as evidenced by the altered ECG
      pattern with ST-segment elevation and an increase in the levels of cardiac injury
      markers including troponin-I, creatine kinase-MB, alanine transaminase, aspartate
      transaminase, lactate dehydrogenase; inflammatory markers, interleukine-6 and
      tumor necrosis factor. In this group, there was also an increase in cardiac lipid
      peroxidation and a decrease in cellular antioxidants. However, pretreatment with
      ACC maintained the normal ECG pattern and nearly normal levels of all the cardiac
      markers in ISO-induced animals. Electron microscopic and histological studies
      also showed marked reduction in ISO-induced cardiac damages including infarct
      size by ACC. Analysis by 2-DE revealed the involvement of 19 different cardiac
      proteins, associated with energy metabolism, oxidative stress and maintenance of
      cytoskeleton. The expression of those proteins were altered by ISO, but
      maintained in ACC pretreated rats. Our findings reveal the potential of isolated
      ACC in the prevention of myocardial damage.

PMID- 29170392
TI  - Larval Dispersal of Spodoptera frugiperda Strains on Bt Cotton: A Model for
      Understanding Resistance Evolution and Consequences for its Management.
AB  - High dispersal of Lepidoptera larvae between non-Bt and Bt cotton plants can
      favour the evolution of insect resistance; however, information on host
      acceptance of neonates in tropical transgenic crops is scarce. Therefore, the
      purposes of this study were as follows: (i) to investigate the feeding behaviour
      of susceptible and Cry1F-resistant strains of Spodoptera frugiperda (J.E. Smith)
      on Bt and non-Bt cotton (Gossypium hirsutum L.) varieties and (ii) to understand
      the possible effects of cotton field contamination on the dispersal and
      infestation capacity of S. frugiperda larvae by using an individual-based model.
      The main results of this paper are as follows: (1) the highest post-feeding
      larval dispersal of the Cry1F-resistant strain occurred at an exposure time of 18
      24 h; (2) via video tracking assays, we found that the least distance moved was
      by larvae resistant to Cry1F on non-Bt cotton; and (3) the model indicated
      differences in mobility capacity between Bt and non-Bt cotton. We conclude that
      resistant neonates exhibit sedentary behaviour. Our report represents the first
      findings concerning the fitness cost of larval behaviour traits of S. frugiperda
      associated with Cry1F resistance in Brazilian populations.

PMID- 29170393
TI  - An in vivo biosensing, biomimetic electrochemical transistor with applications in
      plant science and precision farming.
AB  - The in vivo monitoring of key plant physiology parameters will be a key enabler
      of precision farming. Here, a biomimetic textile-based biosensor, which can be
      inserted directly into plant tissue is presented: the device is able to monitor,
      in vivo and in real time, variations in the solute content of the plant sap. The
      biosensor has no detectable effect on the plant's morphology even after six weeks
      of continuous operation. The continuous monitoring of the sap electrolyte
      concentration in a growing tomato plant revealed a circadian pattern of
      variation. The biosensor has the potential to detect the signs of abiotic stress,
      and therefore might be exploited as a powerful tool to study plant physiology and
      to increase tomato growth sustainability. Also, it can continuously communicate
      the plant health status, thus potentially driving the whole farm management in
      the frame of smart agriculture.

PMID- 29170394
TI  - Quantifying protein densities on cell membranes using super-resolution optical
      fluctuation imaging.
AB  - Quantitative approaches for characterizing molecular organization of cell
      membrane molecules under physiological and pathological conditions profit from
      recently developed super-resolution imaging techniques. Current tools employ
      statistical algorithms to determine clusters of molecules based on single
      molecule localization microscopy (SMLM) data. These approaches are limited by the
      ability of SMLM techniques to identify and localize molecules in densely
      populated areas and experimental conditions of sample preparation and image
      acquisition. We have developed a robust, model-free, quantitative clustering
      analysis to determine the distribution of membrane molecules that excels in
      densely labeled areas and is tolerant to various experimental conditions, i.e.
      multiple-blinking or high blinking rates. The method is based on a TIRF
      microscope followed by a super-resolution optical fluctuation imaging (SOFI)
      analysis. The effectiveness and robustness of the method is validated using
      simulated and experimental data investigating nanoscale distribution of CD4
      glycoprotein mutants in the plasma membrane of T cells.

PMID- 29170396
TI  - An estimate of diapycnal nutrient fluxes to the euphotic zone in the Florida
      Straits.
AB  - A recent hydrographic survey of the Florida Current at 27 degrees N revealed an
      enhanced upward flux of nutrients along the Florida coast. Geostrophic flow of
      the Gulf Stream through the narrow Florida Straits causes an uplift of the
      nutricline toward its western edge, shoaling the mixed layers into the base of
      the euphotic zone. At a nearshore station, nitrate, phosphate, and silicate
      concentrations reached 19, 1.4, and 10 uM, respectively, at a water depth of 27
      m. Furthermore, nutrient vertical gradients below the mixed layer increased with
      decreasing seafloor depth toward the Florida coast. The estimated vertical eddy
      diffusive nutrient fluxes across diapycnal surfaces reached 0.40-83.7, 0.03-6.24,
      and 0.24-45.5 mmol m-2 d-1 for nitrate, phosphate, and silicate, respectively,
      along the shore. Estimated fluxes span a wide range due to the range of
      diffusivity measured. The lower end of estimated fluxes are comparable to open
      ocean values, but higher end of estimates are two orders of magnitude greater
      than those observed in open ocean. The diapycnal nutrient fluxes declined rapidly
      offshore as a result of decreasing vertical gradients of nutrient concentration.

PMID- 29170395
TI  - Oncogenic PIK3CA induces centrosome amplification and tolerance to genome
      doubling.
AB  - Mutations in PIK3CA are very frequent in cancer and lead to sustained PI3K
      pathway activation. The impact of acute expression of mutant PIK3CA during early
      stages of malignancy is unknown. Using a mouse model to activate the Pik3ca
      H1047R hotspot mutation in the heterozygous state from its endogenous locus, we
      here report that mutant Pik3ca induces centrosome amplification in cultured cells
      (through a pathway involving AKT, ROCK and CDK2/Cyclin E-nucleophosmin) and in
      mouse tissues, and increased in vitro cellular tolerance to spontaneous genome
      doubling. We also present evidence that the majority of PIK3CA H1047R mutations
      in the TCGA breast cancer cohort precede genome doubling. These previously
      unappreciated roles of PIK3CA mutation show that PI3K signalling can contribute
      to the generation of irreversible genomic changes in cancer. While this can limit
      the impact of PI3K-targeted therapies, these findings also open the opportunity
      for therapeutic approaches aimed at limiting tumour heterogeneity and evolution.

PMID- 29170397
TI  - Methylomic and phenotypic analysis of the ModH5 phasevarion of Helicobacter
      pylori.
AB  - The Helicobacter pylori phase variable gene modH, typified by gene HP1522 in
      strain 26695, encodes a N6-adenosine type III DNA methyltransferase. Our previous
      studies identified multiple strain-specific modH variants (modH1 - modH19) and
      showed that phase variation of modH5 in H. pylori P12 influenced expression of
      motility-associated genes and outer membrane protein gene hopG. However, the
      ModH5 DNA recognition motif and the mechanism by which ModH5 controls gene
      expression were unknown. Here, using comparative single molecule real-time
      sequencing, we identify the DNA site methylated by ModH5 as 5'-Gm6ACC-3'. This
      motif is vastly underrepresented in H. pylori genomes, but overrepresented in a
      number of virulence genes, including motility-associated genes, and outer
      membrane protein genes. Motility and the number of flagella of H. pylori P12 wild
      type were significantly higher than that of isogenic modH5 OFF or DeltamodH5
      mutants, indicating that phase variable switching of modH5 expression plays a
      role in regulating H. pylori motility phenotypes. Using the flagellin A (flaA)
      gene as a model, we show that ModH5 modulates flaA promoter activity in a GACC
      methylation-dependent manner. These findings provide novel insights into the role
      of ModH5 in gene regulation and how it mediates epigenetic regulation of H.
      pylori motility.

PMID- 29170399
TI  - Polarization of the Majorana quasiparticles in the Rashba chain.
AB  - We demonstrate that the selective equal-spin Andreev reflection (SESAR)
      spectroscopy can be used in STM experiments to distinguish the zero-energy
      Majorana quasiparticles from the ordinary fermionic states of the Rashba chain.
      Such technique, designed for probing the p-wave superconductivity, could be
      applied to the intersite pairing of equal-spin electrons in the chain of magnetic
      Fe atoms deposited on the superconducting Pb substrate. Our calculations of the
      effective pairing amplitude for individual spin components imply the magnetically
      polarized Andreev conductance, which can be used to 'filter' the Majorana
      quasiparticles from the ordinary in-gap states, although the pure spin current
      (i.e., perfect polarization) is impossible.

PMID- 29170398
TI  - Arabidopsis RSS1 Mediates Cross-Talk Between Glucose and Light Signaling During
      Hypocotyl Elongation Growth.
AB  - Plants possess exuberant plasticity that facilitates its ability to adapt and
      survive under challenging environmental conditions. The developmental plasticity
      largely depends upon cellular elongation which is governed by a complex network
      of environmental and phytohormonal signals. Here, we report role of glucose (Glc)
      and Glc-regulated factors in controlling elongation growth and shade response in
      Arabidopsis. Glc controls shade induced hypocotyl elongation in a dose dependent
      manner. We have identified a Glc repressed factor REGULATED BY SUGAR AND SHADE1
      (RSS1) encoding for an atypical basic helix-loop-helix (bHLH) protein of unknown
      biological function that is required for normal Glc actions. Phenotype analysis
      of mutant and overexpression lines suggested RSS1 to be a negative regulator of
      elongation growth. RSS1 affects overall auxin homeostasis. RSS1 interacts with
      the elongation growth-promoting proteins HOMOLOG OF BEE2 INTERACTING WITH IBH 1
      (HBI1) and BR ENHANCED EXPRESSION2 (BEE2) and negatively affects the
      transcription of their downstream targets such as YUCs, INDOLE-3-ACETIC ACID
      INDUCIBLE (IAAs), LONG HYPOCOTYL IN FAR-RED1 (HFR1), HOMEOBOX PROTEIN 2 (ATHB2),
      XYLOGLUCAN ENDOTRANSGLUCOSYLASE/HYDROLASES (XTHs) and EXPANSINS. We propose, Glc
      signals might maintain optimal hypocotyl elongation under multiple signals such
      as light, shade and phytohormones through the central growth regulatory bHLH/HLH
      module.

PMID- 29170400
TI  - Host STING-dependent MDSC mobilization drives extrinsic radiation resistance.
AB  - Radiotherapy induces and promotes innate and adaptive immunity in which host
      STING plays an important role. However, radioresistance in irradiated tumors can
      also develop, resulting in relapse. Here we report a mechanism by which extrinsic
      resistance develops after local ablative radiation that relies on the
      immunosuppressive action of STING. The STING/type I interferon pathway enhances
      suppressive inflammation in tumors by recruiting myeloid cells in part via the
      CCR2 pathway. Germ-line knockouts of CCR2 or treatment with an anti-CCR2 antibody
      results in blockade of radiation-induced MDSC infiltration. Treatment with anti
      CCR2 antibody alleviates immunosuppression following activation of the STING
      pathway, enhancing the anti-tumor effects of STING agonists and radiotherapy. We
      propose that radiation-induced STING activation is immunosuppressive due to
      (monocytic) M-MDSC infiltration, which results in tumor radioresistance.
      Furthermore, the immunosuppressive effects of radiotherapy and STING agonists can
      be abrogated in humans by a translational strategy involving anti-CCR2 antibody
      treatment to improve radiotherapy.

PMID- 29170401
TI  - Functional diversity of topological modules in human protein-protein interaction
      networks.
AB  - A large-scale molecular interaction network of protein-protein interactions
      (PPIs) enables the automatic detection of molecular functional modules through a
      computational approach. However, the functional modules that are typically
      detected by topological community detection algorithms may be diverse in
      functional homogeneity and are empirically considered to be default functional
      modules. Thus, a significant challenge that has been described but not elucidated
      is investigating the relationship between topological modules and functional
      modules. We systematically investigated this issue by initially using seven
      widely used community detection algorithms to partition the PPI network into
      communities. Four homogeneity measures were subsequently implemented to evaluate
      the functional homogeneity of protein community. We determined that a significant
      portion of topological modules with heterogeneous functionality exists and should
      be further investigated; moreover, these findings indicated that topologically
      based functional module detection approaches must be reconsidered. Furthermore,
      we found that the functional homogeneity of topological modules is positively
      correlated with their edge densities, degree of association with diseases and
      general Gene Ontology (GO) terms. Thus, topologically based module detection
      approaches should be used with caution in the identification of functional
      modules with high homogeneity.

PMID- 29170402
TI  - Publisher Correction: Small molecule inhibition of cGAS reduces interferon
      expression in primary macrophages from autoimmune mice.
AB  - The previously published version of this Article contained errors in Fig. 6. In
      panel h the units of the x axis were incorrectly given as mM and should have been
      given as uM. Also, the IC50s for RU.365, RU.332 and RU.521 within panel h were
      incorrectly given as mM and should have been given as uM. These errors have been
      corrected in both the PDF and HTML versions of the Article.

PMID- 29170403
TI  - Coalescent-based delimitation outperforms distance-based methods for delineating
      less divergent species: the case of Kurixalus odontotarsus species group.
AB  - Few empirical studies have compared coalescent-based methods to distance-based
      methods for delimitation of less divergent species. In this study, we used two
      coalescent-based (BFD and BPP) and two distance-based barcoding (ABGD and jMOTU)
      methods to delimit closely related species in the Kurixalus odontotarsus species
      group. Phylogenetic analyses revealed that the K. odontotarsus species group
      comprises 11 distinct maternal clades with strong support values. Based on the
      genetic and morphological evidences, we consider that species diversity in the K.
      odontotarsus species group was underestimated and the 11 clades represent 11
      species, of which six are unnamed. The coalescent-based delimitations decisively
      supported the scenario of 11-species corresponding to the 11 clades. However, the
      distance-based ABGD only obtained 3-6 candidate species, which is not consistent
      with morphological evidence. These results indicate that BFD and BPP are more
      conservative than ABGD to false negatives (lumping). Method of fixed threshold
      (jMOTU) may obtain a resolution similar to that inferred by BFD and BPP, but it
      severely relies on subjective choice of the threshold and lacks statistical
      support. We consider that coalescent-based BFD and BPP approaches outperform
      distance-based methods for delineation of less divergent species.

PMID- 29170404
TI  - A galactic microquasar mimicking winged radio galaxies.
AB  - A subclass of extragalactic radio sources known as winged radio galaxies has
      puzzled astronomers for many years. The wing features are detected at radio
      wavelengths as low-surface-brightness radio lobes that are clearly misaligned
      with respect to the main lobe axis. Different models compete to account for these
      peculiar structures. Here, we report observational evidence that the parsec-scale
      radio jets in the Galactic microquasar GRS 1758-258 give rise to a Z-shaped radio
      emission strongly reminiscent of the X and Z-shaped morphologies found in winged
      radio galaxies. This is the first time that such extended emission features are
      observed in a microquasar, providing a new analogy for its extragalactic
      relatives. From our observations, we can clearly favour the hydrodynamic backflow
      interpretation against other possible wing formation scenarios. Assuming that
      physical processes are similar, we can extrapolate this conclusion and suggest
      that this mechanism could also be at work in many extragalactic cases.

PMID- 29170405
TI  - The Robustness and the Doubly-Preferential Attachment Simulation of the Consensus
      Connectome Dynamics of the Human Brain.
AB  - Consensus Connectome Dynamics (CCD) is a remarkable phenomenon of the human
      connectomes (braingraphs) that was discovered by continuously decreasing the
      minimum confidence-parameter at the graphical interface of the Budapest Reference
      Connectome Server, which depicts the cerebral connections of n = 418 subjects
      with a frequency-parameter k: For any k = 1, 2, ..., n one can view the graph of
      the edges that are present in at least k connectomes. If parameter k is decreased
      one-by-one from k = n through k = 1 then more and more edges appear in the graph,
      since the inclusion condition is relaxed. The surprising observation is that the
      appearance of the edges is far from random: it resembles a growing, complex
      structure. We hypothesize that this growing structure copies the axonal
      development of the human brain. Here we show the robustness of the CCD
      phenomenon: it is almost independent of the particular choice of the set of
      underlying connectomes. This result shows that the CCD phenomenon is most likely
      a biological property of the human brain and not just a property of the data sets
      examined. We also present a simulation that well-describes the growth of the CCD
      structure: in our random graph model a doubly-preferential attachment
      distribution is found to mimic the CCD.

PMID- 29170406
TI  - An extracellular matrix-related prognostic and predictive indicator for early
      stage non-small cell lung cancer.
AB  - The prognosis and prediction of adjuvant chemotherapy (ACT) response in early
      stage non-small cell lung cancer (NSCLC) patients remain poor in this era of
      personalized medicine. We hypothesize that extracellular matrix (ECM)-associated
      components could be potential markers for better diagnosis and prognosis due to
      their differential expression in 1,943 primary NSCLC tumors as compared to 303
      normal lung tissues. Here we develop a 29-gene ECM-related prognostic and
      predictive indicator (EPPI). We validate a robust performance of the EPPI risk
      scoring system in multiple independent data sets, comprising a total of 2,071
      early-stage NSCLC tumors. Patients are stratified according to the universal
      cutoff score based on the EPPI when applied in the clinical setting; the low-risk
      group has significantly better survival outcome. The functional EPPI gene set
      represents a potential genomic tool to improve patient selection in early-stage
      NSCLC to further derive the best benefits of ACT and prevent unnecessary
      treatment or ACT-associated morbidity.

PMID- 29170407
TI  - Higher risk sexual behaviour is associated with unawareness of HIV-positivity and
      lack of viral suppression - implications for Treatment as Prevention.
AB  - Efficacy of Treatment as Prevention Strategy depends on a variety of factors
      including individuals' likelihood to test and initiate treatment, viral load and
      sexual behaviour. We tested the hypothesis that people with higher risk sexual
      behaviour are less likely to know their HIV-positive status and be virologically
      suppressed. A cross-sectional population-based survey of individuals aged 15-59
      years old was conducted in 2013 in KwaZulu-Natal, South Africa. A two-stage
      cluster probability sampling was used. After adjustment for age and sex, lack of
      awareness of HIV-positivity was strongly associated with having more than one
      sexual partner in the preceding year (aOR: 2.1, 95%CI: 1.5-3.1). Inconsistent
      condom use was more common in individuals with more than one sexual partner (aOR:
      16.6, 95%CI: 7.6-36.7) and those unaware (aOR: 3.7, 95%CI: 2.6-5.4). Among people
      aware of their HIV-positivity, higher risk sexual behaviour was associated with
      lack of viral suppression (aOR: 2.2, 95%CI: 1.1-4.5). Risky sexual behaviour
      seems associated with factors linked to poor health-seeking behaviour which may
      have negative implications for HIV testing and Treatment as Prevention.
      Innovative strategies, driven by improved epidemiological and anthropological
      understanding, are needed to enable comprehensive approaches to HIV prevention.

PMID- 29170408
TI  - Identification of the Binding Sites on Rab5 and p110beta Phosphatidylinositol 3
      kinase.
AB  - Rab5 is a small monomeric GTPase that mediates protein trafficking during
      endocytosis. Inactivation of Rab5 by GTP hydrolysis causes a conformational
      change that masks binding sites on its "switch regions" from downstream
      effectors. The p85 subunit of phosphatidylinositol 3-kinase (PI3K) is a GTPase
      activating protein (GAP) towards Rab5. Whereas p85 can bind with both Rab5-GTP
      and Rab5-GDP, the PI3K catalytic subunit p110beta binds only Rab5-GTP, suggesting
      it interacts with the switch regions. Thus, the GAP functions of the catalytic
      arginine finger (from p85) and switch region stabilization (from p110beta) may be
      provided by both proteins, acting together. To identify the Rab5 residues
      involved in binding p110beta, residues in the Rab5 switch regions were mutated. A
      stabilized recombinant p110 protein, where the p85-iSH2 domain was fused to p110
      (alpha or beta) was used in binding experiments. Eleven Rab5 mutants, including
      E80R and H83E, showed reduced p110beta binding. The Rab5 binding site on p110beta
      was also resolved through mutation of p110beta in its Ras binding domain, and
      includes residues I234, E238 and Y244. This is a second region within p110beta
      important for Rab5 binding. The Rab5-GTP:p110beta interaction may be further
      elucidated through the characterization of these non-binding mutants in cells.

PMID- 29170409
TI  - Topology-commanded optical properties of bistable electric-field-induced torons
      in cholesteric bubble domains.
AB  - Nowadays, complicated topological defects enable many experimental manipulations
      and configurational simulations of active soft matter for optical and photonic
      applications. Investigation of topological defects in soft anisotropic materials
      enables one to better understand three-dimensional orientation fields in
      cholesteric liquid crystals. Here, we describe optical properties of bistable
      bubble domain (BD) texture torons in a thin layer of cholesteric liquid crystal
      (CLC), frustrated by homeotropic anchoring conditions, and reliably switchable by
      a random process. The control of macroscopic optical density and diffraction
      efficiency of the BD texture is demonstrated by a selection of a confinement
      ratio of the CLC. Experimentally reconstructed CLC director profile reveals the
      topology of BD torons allowing consideration of naturally occurring BD texture
      for applications in optical and photonic devices, which are bistably switchable
      between active and transparent optical states.

PMID- 29170410
TI  - Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by
      binding and releasing nitric oxide.
AB  - Nitric oxide (NO) produced by endothelial cells in response to cytokines displays
      anti-inflammatory activity by preventing the adherence, migration and activation
      of neutrophils. The molecular mechanism by which NO operates at the blood
      endothelium interface to exert anti-inflammatory properties is largely unknown.
      Here we show that on endothelial surfaces, NO is associated with the sulfhydryl
      rich protein tissue transglutaminase (TG2), thereby endowing the membrane
      surfaces with anti-inflammatory properties. We find that tumor necrosis factor
      alpha-stimulated neutrophil adherence is opposed by TG2 molecules that are bound
      to the endothelial surface. Alkylation of cysteine residues in TG2 or inhibition
      of endothelial NO synthesis renders the surface-bound TG2 inactive, whereas
      specific, high affinity binding of S-nitrosylated TG2 (SNO-TG2) to endothelial
      surfaces restores the anti-inflammatory properties of the endothelium, and
      reconstitutes the activity of endothelial-derived NO. We also show that SNO-TG2
      is present in healthy tissues and that it forms on the membranes of shear
      activated endothelial cells. Thus, the anti-inflammatory mechanism that prevents
      neutrophils from adhering to endothelial cells is identified with TG2 S
      nitrosylation at the endothelial cell-blood interface.

PMID- 29170411
TI  - Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry.
AB  - Hepatitis C virus (HCV) is one of the leading causes of liver diseases and
      transplantation worldwide. The current available therapy for HCV infection is
      based on interferon-alpha, ribavirin and the new direct-acting antivirals (DAAs),
      such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of
      drug design, severe side effects and HCV resistance presented by the existing
      treatments demonstrate the need for developing more efficient anti-HCV agents.
      This study aimed to evaluate the antiviral effects of sorbifolin (1) and
      pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle.
      These compounds were investigated for their anti-HCV activities using genotype 2a
      JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2
      inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic
      concentrations. The mechanism of the flavonoid 2 block to virus entry was
      demonstrated to be by both the direct action on virus particles and the
      interference on the host cells. Alternatively, the flavonoid 1 activity was
      restricted to its virucidal effect. Additionally, no inhibitory effects on HCV
      replication and release were observed by treating cells with these flavonoids.
      These data are the first description of 1 and 2 possessing in vitro anti-HCV
      activity.

PMID- 29170412
TI  - Ischemic Postconditioning Protects Against Intestinal Ischemia/Reperfusion Injury
      via the HIF-1alpha/miR-21 Axis.
AB  - Intestinal ischemia/reperfusion (I/R) can lead to tissue damage associated with
      inflammation and mucosal apoptosis. Ischemic postconditioning (IPostC), a series
      of repeated, brief, intermittent periods of ischemia and reperfusion, has
      beneficial effects against I/R-induced injury in the heart and intestine,
      although the underlying mechanisms for these effects remain unclear. We evaluated
      the involvement of microRNA-21 (miR-21) in the protective effects of IPostC in a
      rat model of I/R induced by superior mesenteric artery occlusion and reopening.
      IPostC decreased I/R injury and suppressed apoptosis in the intestinal tissues
      concomitant with the induction of hypoxia inducible factor 1 alpha (HIF-1alpha)
      and the upregulation of miR-21. In vitro experiments in the intestinal epithelial
      cell line IEC-6 showed that hypoxia induced miR-21 and this effect was abolished
      by silencing HIF1-alpha, confirming the induction of miR-21 by HIF1-alpha, HIF1
      alpha or miR-21 inhibition exacerbated I/R induced apoptosis, and programmed cell
      death 4 (PDCD4) and Fas-L was involved in miR-21 mediated anti-apoptotic effects
      on intestinal epithelial cells. Knockdown of miR-21 or inhibition of HIF1-alpha
      abolished the IPostC-mediated attenuation of intestinal injury and apoptosis and
      the downregulation of PDCD4 and Fas-L. A potential mechanism underlying the
      protective effect of IPostC may therefore involve the induction of miR-21 by HIF1
      alpha and the attenuation of apoptosis via the downregulation of PDCD4 and Fas-L.

PMID- 29170414
TI  - Tailoring the structural, morphological, optical and dielectric properties of
      lead iodide through Nd3+ doping.
AB  - Hexagonal single crystal nanosheets of Nd3+ doped PbI2 were effortlessly
      synthesized via microwave-assisted technique under a power of 700 W and in a
      duration of 15 minutes with a homogeneous morphology. X-ray diffraction, energy
      dispersive X-ray spectroscope, scanning electron microscope, FT-Raman, UV
      Visible, photoluminescence and dielectric measurement were employed to study the
      product. High purity, single phase and presence of Nd3+ doping was confirmed. SEM
      study confirm the formation of nanorods and single crystal nanosheets of very few
      nanometers in size. Robust vibrational analysis has been carried out and the
      observed bands are assigned to the vibration modes of E21, A11, A12, 2E21 and
      2E11, respectively. These bands are red-shifted when compare to the corresponding
      bulk values which indicate relaxed nanostructure formation and occurrence of
      confinement effect. The thickness of the synthesized single crystal nanosheets
      are found to be in the range of ~20 to 30 nm. The energy band gap was calculated
      and found to be 3.35, 3.34, 3.42 and 3.39 eV for pure, 1, 3 and 5% Nd3+ doped
      lead iodide, respectively. The clear blue luminescence has been observed at 440
      nm and 466 nm when excited at 250 nm and 280 nm respectively. Dielectric and ac
      electrical conductivity was also measured and discussed.

PMID- 29170413
TI  - MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal
      adenocarcinoma associated with poor outcome and chemoresistance.
AB  - Intratumoral phenotypic heterogeneity has been described in many tumor types,
      where it can contribute to drug resistance and disease recurrence. We analyzed
      ductal and neuroendocrine markers in pancreatic ductal adenocarcinoma, revealing
      heterogeneous expression of the neuroendocrine marker Synaptophysin within ductal
      lesions. Higher percentages of Cytokeratin-Synaptophysin dual positive tumor
      cells correlate with shortened disease-free survival. We observe similar lineage
      marker heterogeneity in mouse models of pancreatic ductal adenocarcinoma, where
      lineage tracing indicates that Cytokeratin-Synaptophysin dual positive cells
      arise from the exocrine compartment. Mechanistically, MYC binding is enriched at
      neuroendocrine genes in mouse tumor cells and loss of MYC reduces ductal
      neuroendocrine lineage heterogeneity, while deregulated MYC expression in KRAS
      mutant mice increases this phenotype. Neuroendocrine marker expression is
      associated with chemoresistance and reducing MYC levels decreases gemcitabine
      induced neuroendocrine marker expression and increases chemosensitivity.
      Altogether, we demonstrate that MYC facilitates ductal-neuroendocrine lineage
      plasticity in pancreatic ductal adenocarcinoma, contributing to poor survival and
      chemoresistance.

PMID- 29170415
TI  - Antagonistic bacteria disrupt calcium homeostasis and immobilize algal cells.
AB  - Photosynthetic unicellular organisms, known as microalgae, are key contributors
      to carbon fixation on Earth. Their biotic interactions with other microbes shape
      aquatic microbial communities and influence the global photosynthetic capacity.
      So far, limited information is available on molecular factors that govern these
      interactions. We show that the bacterium Pseudomonas protegens strongly inhibits
      the growth and alters the morphology of the biflagellated green alga
      Chlamydomonas reinhardtii. This antagonistic effect is decreased in a bacterial
      mutant lacking orfamides, demonstrating that these secreted cyclic lipopeptides
      play an important role in the algal-bacterial interaction. Using an aequorin Ca2+
      reporter assay, we show that orfamide A triggers an increase in cytosolic Ca2+ in
      C. reinhardtii and causes deflagellation of algal cells. These effects of
      orfamide A, which are specific to the algal class of Chlorophyceae and appear to
      target a Ca2+ channel in the plasma membrane, represent a novel biological
      activity for cyclic lipopeptides.

PMID- 29170417
TI  - Remotely Triggered Locomotion of Hydrogel Mag-bots in Confined Spaces.
AB  - In this study, soft hydrogel crawlers with remote magnetic-responsive motility in
      confined spaces have been developed. Inspired by the motion of maggots, the
      hydrogel crawlers can reversibly contract and elongate their body controlled by
      repeatedly switching on/off an alternating magnetic field. Based on the cyclic
      deformation, the hydrogel crawlers can move peristaltically in a confined space
      that is coated with asymmetric micro-patterns. The dependence of the hydrogel
      motility on the pattern structures and lubrication is characterized using
      experimental measurements. Such a hydrogel system pioneers the study of active
      motile systems in porous media and has the potential to impact the fields of
      targeted drug delivery and active actuators.

PMID- 29170416
TI  - Ultrafast non-radiative dynamics of atomically thin MoSe2.
AB  - Photo-induced non-radiative energy dissipation is a potential pathway to induce
      structural-phase transitions in two-dimensional materials. For advancing this
      field, a quantitative understanding of real-time atomic motion and lattice
      temperature is required. However, this understanding has been incomplete due to a
      lack of suitable experimental techniques. Here, we use ultrafast electron
      diffraction to directly probe the subpicosecond conversion of photoenergy to
      lattice vibrations in a model bilayered semiconductor, molybdenum diselenide. We
      find that when creating a high charge carrier density, the energy is efficiently
      transferred to the lattice within one picosecond. First-principles nonadiabatic
      quantum molecular dynamics simulations reproduce the observed ultrafast increase
      in lattice temperature and the corresponding conversion of photoenergy to lattice
      vibrations. Nonadiabatic quantum simulations further suggest that a softening of
      vibrational modes in the excited state is involved in efficient and rapid energy
      transfer between the electronic system and the lattice.

PMID- 29170418
TI  - Gene Therapy Restores Mfrp and Corrects Axial Eye Length.
AB  - Hyperopia (farsightedness) is a common and significant cause of visual
      impairment, and extreme hyperopia (nanophthalmos) is a consequence of loss-of
      function MFRP mutations. MFRP deficiency causes abnormal eye growth along the
      visual axis and significant visual comorbidities, such as angle closure glaucoma,
      cystic macular edema, and exudative retinal detachment. The Mfrp rd6 /Mfrp rd6
      mouse is used as a pre-clinical animal model of retinal degeneration, and we
      found it was also hyperopic. To test the effect of restoring Mfrp expression, we
      delivered a wild-type Mfrp to the retinal pigmented epithelium (RPE) of Mfrp rd6
      /Mfrp rd6 mice via adeno-associated viral (AAV) gene therapy. Phenotypic rescue
      was evaluated using non-invasive, human clinical testing, including fundus auto
      fluorescence, optical coherence tomography, electroretinography, and ultrasound.
      These analyses showed gene therapy restored retinal function and normalized axial
      length. Proteomic analysis of RPE tissue revealed rescue of specific proteins
      associated with eye growth and normal retinal and RPE function. The favorable
      response to gene therapy in Mfrp rd6 /Mfrp rd6 mice suggests hyperopia and
      associated refractive errors may be amenable to AAV gene therapy.

PMID- 29170420
TI  - Publisher Correction: Orbital bistatic radar observations of asteroid Vesta by
      the Dawn mission.
AB  - An incorrect version of the Supplementary Information was inadvertently published
      with this Article. The HTML has now been updated to include the correct version
      of the Supplementary Information.

PMID- 29170419
TI  - PDGFR Signaling Mediates Hyperproliferation and Fibrotic Responses of Subsynovial
      Connective Tissue Cells in Idiopathic Carpal Tunnel Syndrome.
AB  - Fibrosis of the subsynovial connective tissue (SSCT) is a pathognomonic change in
      carpal tunnel syndrome (CTS). Identification of molecular targets and anti
      fibrotic therapies could provide new treatment strategies for CTS. The
      contribution of SSCT cells to fibrosis and the signaling pathways that initiate
      and aggravate fibrosis in CTS remain unknown. Here we report that platelet
      derived growth factor receptor alpha (PDGFRalpha) positive ( + ) cells accumulate
      in CTS SSCT and that the presence of fibrotic growth factor, PDGF-AA, results in
      increased proliferation of PDGFRalpha+ cells via PI3K/Akt signaling pathway.
      Although PI3K inhibition decreased proliferation, there was no change in fibrosis
      related gene expression. Indeed, protein levels of fibrosis signaling mediator
      TGF-beta remained the same and the second messenger, Smad2/3, accumulated in the
      nucleus. In contrast AMP-activated protein kinase (AMPK) activation, which can be
      induced with metformin and AICAR inhibited proliferation, TGF-beta expression,
      and altered cell morphology in SSCT cells. Further we show that AMPK activation
      by metformin reduced collagen III levels and the ratio of Collagen I to Collagen
      III. Both AICAR and metformin reduced F-actin and significantly reduced the fiber
      cross alignment. Our results suggest that PDGFRa signaling may be an important
      fibrosis target and that activators of AMPK, may be an important therapeutic
      approach for treating CTS.

PMID- 29170421
TI  - Resident Microbiome Disruption with Antibiotics Enhances Virulence of a
      Colonizing Pathogen.
AB  - There is growing evidence that symbiotic microbes play key roles in host defense,
      but less is known about how symbiotic microbes mediate pathogen-induced damage to
      hosts. Here, we use a natural wildlife disease system, house finches and the
      conjunctival bacterial pathogen Mycoplasma gallisepticum (MG), to experimentally
      examine the impact of the ocular microbiome on host damage and pathogen virulence
      factors during infection. We disrupted the ocular bacterial community of healthy
      finches using an antibiotic that MG is intrinsically resistant to, then
      inoculated antibiotic- and sham-treated birds with MG. House finches with
      antibiotic-disrupted ocular microbiomes had more severe MG-induced conjunctival
      inflammation than birds with unaltered microbiomes, even after accounting for
      differences in conjunctival MG load. Furthermore, MG cultures from finches with
      disrupted microbiomes had increased sialidase enzyme and cytadherence activity,
      traits associated with enhanced virulence in Mycoplasmas, relative to isolates
      from sham-treated birds. Variation in sialidase activity and cytadherence among
      isolates was tightly linked with degree of tissue inflammation in hosts,
      supporting the consideration of these traits as virulence factors in this system.
      Overall, our results suggest that microbial dysbiosis can result in enhanced
      virulence of colonizing pathogens, with critical implications for the health of
      wildlife, domestic animals, and humans.

PMID- 29170423
TI  - Bamboo sheath-A modified branch based on the anatomical observations.
AB  - Culm sheath has always been considered a modified leaf. In this study, the
      anatomical structure of the culm sheath from Fargesia yunnanensis was analyzed to
      determine whether it originated from the foliage leaf blade or from the branch.
      The vascular bundles of the culm sheath showed greater similarity to the branches
      in shape and anatomical structure. In contrast to foliage blades, there are no
      midribs in culm sheaths. Stomatal density in the culm sheath is greater in the
      adaxial than it is in the abaxial epidermis, which is the opposite of that found
      in foliage leaf blades, and that density shows greater similarity to branches
      than it does to foliage blades. Fusoid cells are distributed on both sites of the
      vascular bundles in foliage blades, whereas culm sheaths have, instead, a few
      parenchyma cells that disintegrate and form air cavities when the sheath matures.
      Additionally, the culm sheath has no bulliform cells or trichome in its
      epidermis, and the shape of its long cells shows greater similarity to those of
      branches. Therefore, culm sheath is a modified branch, rather than a modified
      leaf.

PMID- 29170422
TI  - Species composition and environmental adaptation of indigenous Chinese cattle.
AB  - Indigenous Chinese cattle combine taurine and indicine origins and occupy a broad
      range of different environments. By 50 K SNP genotyping we found a discontinuous
      distribution of taurine and indicine cattle ancestries with extremes of less than
      10% indicine cattle in the north and more than 90% in the far south and southwest
      China. Model-based clustering and f4-statistics indicate introgression of both
      banteng and gayal into southern Chinese cattle while the sporadic yak influence
      in cattle in or near Tibetan area validate earlier findings of mitochondrial DNA
      analysis. Geographic patterns of taurine and indicine mitochondrial and Y
      chromosomal DNA diversity largely agree with the autosomal cline. The geographic
      distribution of the genomic admixture of different bovine species is proposed to
      be the combined effect of prehistoric immigrations, gene flow, major rivers
      acting as genetic barriers, local breeding objectives and environmental
      adaptation. Whole-genome scan for genetic differentiation and association
      analyses with both environmental and morphological covariables are remarkably
      consistent with previous studies and identify a number of genes implicated in
      adaptation, which include TNFRSF19, RFX4, SP4 and several coat color genes. We
      propose indigenous Chinese cattle as a unique and informative resource for gene
      level studies of climate adaptation in mammals.

PMID- 29170424
TI  - p300-mediated acetylation increased the protein stability of HIPK2 and enhanced
      its tumor suppressor function.
AB  - Homeodomain-interacting protein kinase 2 (HIPK2) is a nuclear serine/threonine
      kinase that functions in development and tumor suppression. One of the prominent
      features of this kinase is that it is tightly regulated by proteasomal
      degradation. In the present study, we present evidence suggesting that the
      protein stability of HIPK2 can be regulated by p300-mediated acetylation. p300
      increased the protein level of HIPK2 via its acetyltransferase activity. p300
      increased the acetylation of HIPK2 while decreased polyubiquitination and its
      proteasomal degradation. We also observed that DNA damage induced acetylation of
      HIPK2 along with an increase in the protein amount, which was inhibited by p300
      RNAi. Importantly, p300 promoted p53 activation and the HIPK2-mediated
      suppression of cell proliferation, suggesting acetylation-induced HIPK2
      stabilization contributed to the enhanced activation of HIPK2. Overexpression of
      p300 promoted the HIPK2-mediated suppression of tumor growth in mouse xenograft
      model as well. Taken together, our data suggest that p300-mediated acetylation of
      HIPK2 increases the protein stability of HIPK2 and enhances its tumor suppressor
      function.

PMID- 29170425
TI  - TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the
      absence of RIP3.
AB  - Receptor-interacting protein kinase 3 (RIP3) is a critical initiator in mediating
      necroptosis induced by tumor necrosis factor alpha (TNFalpha) in L929 cells, so
      knockdown of RIP3 inhibits TNFalpha-induced L929 cell necroptosis. However, RIP3
      knockdown was shown to switch TNFalpha-induced necroptosis to apoptosis in L929
      cells in other studies. Therefore, whether RIP3 knockdown blocks the TNFalpha
      induced death of L929 cells is controversial. In this study, TNFalpha activated
      caspase pathway and induced cell death in RIP3 knockdown L929 cells, and the RIP3
      independent cell death had been blocked by Z-VAD-FMK (pan-caspase inhibitor) or
      caspase 8 knockdown, demonstrating that RIP3 knockdown switched TNFalpha-induced
      necroptosis to caspase-dependent apoptosis. Although both TNF receptor type 1
      associated death domain protein (TRADD) and RIP1 have been reported to mediate
      TNFalpha-induced apoptosis, the knockdown of TRADD, but not RIP1, suppressed
      TNFalpha-induced activation of the caspase pathway and subsequent apoptosis in
      RIP3 knockdown L929 cells. In addition, TRADD bound and activated caspase 8
      during the RIP3-independent apoptosis process, indicating that TRADD initiates
      RIP3-independent apoptosis by activating the caspase pathway. Collectively, we
      identified the target and mechanism underlying RIP3-independent apoptosis and
      elucidated the coordinated roles of RIP3 and TRADD in mediating the programmed
      cell death of L929 cells following TNFalpha stimulation.

PMID- 29170426
TI  - Non-Invasive whole-body detection of complement activation using radionuclide
      imaging in a mouse model of myocardial ischaemia-reperfusion injury.
AB  - Complement activation is a recognised mediator of myocardial ischaemia
      reperfusion-injury (IRI) and cardiomyocytes are a known source of complement
      proteins including the central component C3, whose activation products can
      mediate tissue inflammation, cell death and profibrotic signalling. We
      investigated the potential to detect and quantify the stable covalently bound
      product C3d by external body imaging, as a marker of complement activation in
      heart muscle in a murine model of myocardial IRI. We used single-photon-emission
      computed-tomography (SPECT) in conjunction with 99mTechnecium-labelled
      recombinant complement receptor 2 (99mTc-rCR2), which specifically detects C3d at
      the site of complement activation. Compared to control imaging with an inactive
      CR2 mutant (99mTc-K41E CR2) or an irrelevant protein (99mTc-PSMA) or using 99mTc
      rCR2 in C3-deficient mice, the use of 99mTc-rCR2 in complement-intact mice gave
      specific uptake in the reperfused myocardium. The heart to skeletal muscle ratio
      of 99mTc-rCR2 was significantly higher than in the three control groups.
      Histological analysis confirmed specific uptake of 99mTc-rCR2. Following
      therapeutic inhibition of complement C3 activation, we found reduced myocardial
      uptake of 99mTc-rCR2. We conclude, therefore that 99mTc-rCR2 imaging can be used
      for non-invasive detection of activated complement and in future could be
      exploited to quantify the severity of myocardial damage due to complement
      activation.

PMID- 29170427
TI  - Genome-wide proteomic profiling reveals the role of dominance protein expression
      in heterosis in immature maize ears.
AB  - Heterosis refers to the phenomenon in which hybrid progeny show superior
      performance relative to their parents. Early maize ear development shows strong
      heterosis in ear architecture traits and greatly affects grain yield. To explore
      the underlying molecular mechanisms, genome-wide proteomics of immature ears of
      maize hybrid ZD909 and its parents were analyzed using tandem mass tag (TMT)
      technology. A total of 9,713 proteins were identified in all three genotypes.
      Among them, 3,752 (38.6%) proteins were differentially expressed between ZD909
      and its parents. Multiple modes of protein action were discovered in the hybrid,
      while dominance expression patterns accounted for 63.6% of the total
      differentially expressed proteins (DEPs). Protein pathway enrichment analysis
      revealed that high parent dominance proteins mainly participated in carbon
      metabolism and nitrogen assimilation processes. Our results suggested that the
      dominant expression of favorable alleles related to C/N metabolism in the hybrid
      may be essential for ZD909 ear growth and heterosis formation. Integrated
      analysis of proteomic and quantitative trait locus (QTL) data further support our
      DEP identification and provide useful information for the discovery of genes
      associated with ear development. Our study provides comprehensive insight into
      the molecular mechanisms underlying heterosis in immature maize ears from a
      proteomic perspective.

PMID- 29170428
TI  - Complex three-dimensional self-assembly in proxies for atmospheric aerosols.
AB  - Aerosols are significant to the Earth's climate, with nearly all atmospheric
      aerosols containing organic compounds that often contain both hydrophilic and
      hydrophobic parts. However, the nature of how these compounds are arranged within
      an aerosol droplet remains unknown. Here we demonstrate that fatty acids in
      proxies for atmospheric aerosols self-assemble into highly ordered three
      dimensional nanostructures that may have implications for environmentally
      important processes. Acoustically trapped droplets of oleic acid/sodium oleate
      mixtures in sodium chloride solution are analysed by simultaneous synchrotron
      small-angle X-ray scattering and Raman spectroscopy in a controlled gas-phase
      environment. We demonstrate that the droplets contained crystal-like lyotropic
      phases including hexagonal and cubic close-packed arrangements of spherical and
      cylindrical micelles, and stacks of bilayers, whose structures responded to
      atmospherically relevant humidity changes and chemical reactions. Further
      experiments show that self-assembly reduces the rate of the reaction of the fatty
      acid with ozone, and that lyotropic-phase formation also occurs in more complex
      mixtures more closely resembling compositions of atmospheric aerosols. We suggest
      that lyotropic-phase formation likely occurs in the atmosphere, with potential
      implications for radiative forcing, residence times and other aerosol
      characteristics.

PMID- 29170430
TI  - Publisher Correction: Multiobjective differential evolution-based multifactor
      dimensionality reduction for detecting gene-gene interactions.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29170429
TI  - Genome-wide meta-analysis in Japanese populations identifies novel variants at
      the TMC6-TMC8 and SIX3-SIX2 loci associated with HbA1c.
AB  - Glycated haemoglobin (HbA1c) is widely used as a biomarker for the diagnosis of
      diabetes, for population-level screening, and for monitoring the glycaemic status
      during medical treatment. Although the heritability of HbA1c has been estimated
      at ~55-75%, a much smaller proportion of phenotypic variance is explained by the
      HbA1c-associated variants identified so far. To search for novel loci influencing
      the HbA1c levels, we conducted a genome-wide meta-analysis of 2 non-diabetic
      Japanese populations (n = 7,704 subjects in total). We identified 2 novel loci
      that achieved genome-wide significance: TMC6-TMC8 (P = 5.3 * 10-20) and SIX3-SIX2
      (P = 8.6 * 10-9). Data from the largest-scale European GWAS conducted for HbA1c
      supported an association between the novel TMC6-TMC8 locus and HbA1c (P = 2.7 *
      10-3). The association analysis with glycated albumin and glycation gap conducted
      using our Japanese population indicated that the TMC6-TMC8 and SIX3-SIX2 loci may
      influence the HbA1c level through non-glycaemic and glycaemic pathways,
      respectively. In addition, the pathway-based analysis suggested that the linoleic
      acid metabolic and 14-3-3-mediated signalling pathways were associated with
      HbA1c. These findings provide novel insights into the molecular mechanisms that
      modulate the HbA1c level in non-diabetic subjects.

PMID- 29170431
TI  - Relative importance of dietary uptake and waterborne exposure for a leaf
      shredding amphipod exposed to thiacloprid-contaminated leaves.
AB  - Systemic neonicotinoids are commonly used in forest pest management programs.
      Senescent leaves containing neonicotinoids may, however, fall from treated trees
      into nearby streams. There, leaf-shredding invertebrates are particularly exposed
      due to their diet (feeding on neonicotinoid-contaminated leaves) or collaterally
      via the water phase (leaching of a neonicotinoid from leaves) - a fact not
      considered during aquatic environmental risk assessment. To unravel the relevance
      of these pathways we used leaves from trees treated with the neonicotinoid
      thiacloprid to subject the amphipod shredder Gammarus fossarum for 21 days (n =
      40) either to dietary, waterborne or a combined (dietary + waterborne) exposure.
      Dietary exposure caused - relative to the control - similar reductions in
      gammarids' leaf consumption (~35%) and lipid content (~20%) as observed for the
      waterborne exposure pathway (30 and 22%). The effect sizes observed under
      combined exposure suggested additivity of effects being largely predictable using
      the reference model "independent action". Since gammarids accumulated -
      independent of the exposure pathway - up to 280 ng thiacloprid/g, dietary
      exposure may also be relevant for predators which prey on Gammarus. Consequently,
      neglecting dietary exposure might underestimate the environmental risk systemic
      insecticides pose for ecosystem integrity calling for its consideration during
      the evaluation and registration of chemical stressors.

PMID- 29170432
TI  - Ocular effects of virtual reality headset wear in young adults.
AB  - Virtual Reality (VR) headsets create immersion by displaying images on screens
      placed very close to the eyes, which are viewed through high powered lenses. Here
      we investigate whether this viewing arrangement alters the binocular status of
      the eyes, and whether it is likely to provide a stimulus for myopia development.
      We compared binocular status after 40-minute trials in indoor and outdoor
      environments, in both real and virtual worlds. We also measured the change in
      thickness of the ocular choroid, to assess the likely presence of signals for
      ocular growth and myopia development. We found that changes in binocular posture
      at distance and near, gaze stability, amplitude of accommodation and stereopsis
      were not different after exposure to each of the 4 environments. Thus, we found
      no evidence that the VR optical arrangement had an adverse effect on the
      binocular status of the eyes in the short term. Choroidal thickness did not
      change after either real world trial, but there was a significant thickening (~10
      microns) after each VR trial (p < 0.001). The choroidal thickening which we
      observed suggest that a VR headset may not be a myopiagenic stimulus, despite the
      very close viewing distances involved.

PMID- 29170433
TI  - Lipoprotein-associated phospholipase A2 and oxidized low-density lipoprotein in
      young patients with acute coronary syndrome in China.
AB  - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered to be a risk
      factor for acute coronary syndrome (ACS), but this remains controversial. This
      study investigated the role of Lp-PLA2 in young Chinese patients with ACS. 228
      young patients (aged <=55 years) with ACS and 237 age-matched controls were
      included. Lp-PLA2 and oxidized low-density lipoprotein (ox-LDL) levels were
      measured by sandwich enzyme-linked immunosorbent assay. Lp-PLA2 levels were
      significantly correlated with smoking, total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C) and ox-LDL levels (all P < 0.05). Multivariate
      logistic regression analysis showed that male sex (OR = 3.25, 95%CI = 1.26-8.38),
      smoking (OR = 3.50, 95%CI = 1.75-7.0), triglyceride (OR = 1.76, 95%CI = 1.08
      2.87), high sensitivity C-reactive protein (hs-CRP) (OR = 2.11, 95%CI = 1.14
      3.90) and ox-LDL (OR = 2.98, 95%CI = 1.72-5.1) were independently associated with
      ACS risk in young patients. Lp-PLA2 was associated with risk of ACS in young
      patients when adjusted for traditional risk factors, including age, sex,
      diabetes, hypertension, smoking, TC, LDL-C, triglyceride and hs-CRP (OR = 1.98,
      95%CI = 1.10-3.56). When further adjusted for ox-LDL levels, the association
      between Lp-PLA2 and ACS became insignificant (OR = 1.69, 95%CI = 0.90-3.17). Lp
      PLA2 was a marker of oxidative stress and inflammation, rather than an
      independent risk factor for ACS in young Chinese patients.

PMID- 29170435
TI  - Biofunctional analysis of Vitellogenin and Vitellogenin receptor in citrus red
      mites, Panonychus citri by RNA interference.
AB  - Panonychus citri is one of the most damaging pests of horticultural crops.
      Conventional control of this pest population through pesticides has led to the
      enhanced pest resistance. Management of P. citri population through RNAi, is
      still largely unknown. In oviparous organisms, fabrication and development of
      yolk protein play a vital role in the reproduction. Vitellin (Vn) is the source
      of eggs storage that helps in proper functioning of Vitellogenin (Vg) and
      Vitellogenin receptor (VgR). VgR is very compulsory protein for the development
      of Vg into oocytes. In the current study, Vg (PcVg) and VgR (PcVgR) genes were
      studied and their expressions at different developmental stages were quantified
      by RT-qPCR. Females treated with dsRNA of PcVg and PcVgR genes exhibited
      reduction in gene expression. Down regulation of target genes significantly
      effected oviposition and reduced the egg laying capacity up to 48% as compared to
      control (ds-egfp). Synergistic effect of target gene's dsRNA was also accessed
      that reduced the egg laying up to 60.42%. Furthermore, combination of target
      dsRNA on deutonymph and protonymph also resulted in 67% and 70% reduction in
      eggs, respectively. Synergistic effect of dsRNA at 1000 ng/ul resulted in longer
      life span as compared to control treatments. This study suggests to develop a new
      strategy of P. citri population control by reducing its reproduction.

PMID- 29170436
TI  - Fate tracing of hepatocytes in mouse liver.
AB  - Hepatocytes perform most of the functions of the liver and are considered
      terminally differentiated cells. Recently, it has been suggested that hepatocytes
      might have the potential to transdifferentiate or dedifferentiate under
      physiological or pathological conditions in vivo. Epithelial-mesenchymal
      transition of hepatocytes in liver fibrosis has also been proposed. However,
      these findings have not been fully confirmed. In this study, hepatocytes were
      genetically labelled for cell fate tracing using lacZ via the tamoxifen-induced
      CreERT/loxP system. After induction with tamoxifen, alb + cells were permanently
      marked by lacZ expression, and all progeny lacZ + cells were derived from a
      single source with no interference. We did not observe transdifferentiation or
      dedifferentiation of hepatocytes into cholangiocytes or hepatic progenitor cells
      under conditions of liver homeostasis or following a 2/3 partial hepatectomy.
      Meanwhile, lacZ/OPN-positive cells were observed in livers of 3,5
      diethoxycarbonyl-1,4-dihydrocollidine-fed mice, and lacZ/alpha-smooth muscle
      actin-positive cells were detected in carbon tetrachloride-induced chronic liver
      injury models. These results suggested that some existing differentiated alb +
      cells might have the potential of transdifferentiation/dedifferentiation or
      epithelial-to-mesenchymal transition in vivo in some liver injury models, but the
      proportion of these alb + cells in liver was very low, and their significance and
      actual function during the pathological process remains to be elucidated.

PMID- 29170434
TI  - Single-cell absolute contact probability detection reveals chromosomes are
      organized by multiple low-frequency yet specific interactions.
AB  - At the kilo- to megabase pair scales, eukaryotic genomes are partitioned into
      self-interacting modules or topologically associated domains (TADs) that
      associate to form nuclear compartments. Here, we combine high-content super
      resolution microscopies with state-of-the-art DNA-labeling methods to reveal the
      variability in the multiscale organization of the Drosophila genome. We find that
      association frequencies within TADs and between TAD borders are below ~10%,
      independently of TAD size, epigenetic state, or cell type. Critically, despite
      this large heterogeneity, we are able to visualize nanometer-sized epigenetic
      domains at the single-cell level. In addition, absolute contact frequencies
      within and between TADs are to a large extent defined by genomic distance, higher
      order chromosome architecture, and epigenetic identity. We propose that TADs and
      compartments are organized by multiple, small-frequency, yet specific
      interactions that are regulated by epigenetics and transcriptional state.

PMID- 29170437
TI  - The responses of cancer cells to PLK1 inhibitors reveal a novel protective role
      for p53 in maintaining centrosome separation.
AB  - Polo-like kinase-1 (PLK1) plays a major role in driving mitotic events, including
      centrosome disjunction and separation, and is frequently over-expressed in human
      cancers. PLK1 inhibition is a promising therapeutic strategy and works by
      arresting cells in mitosis due to monopolar spindles. The p53 tumour suppressor
      protein is a short-lived transcription factor that can inhibit the growth, or
      stimulate the death, of developing cancer cells. Curiously, although p53 normally
      acts in an anti-cancer capacity, it can offer significant protection against
      inhibitors of PLK1, but the events underpinning this effect are not known. Here,
      we show that functional p53 reduces the sensitivity to PLK1 inhibitors by
      permitting centrosome separation to occur, allowing cells to traverse mitosis and
      re-enter cycle with a normal complement of 2N chromosomes. Protection entails the
      activation of p53 through the DNA damage-response enzymes, ATM and ATR, and
      requires the phosphorylation of p53 at the key regulatory site, Ser15. These data
      highlight a previously unrecognised link between p53, PLK1 and centrosome
      separation that has therapeutic implications for the use of PLK1 inhibitors in
      the clinic.

PMID- 29170438
TI  - Solar energy converters based on multi-junction photoemission solar cells.
AB  - Multi-junction solar cells with multiple p-n junctions made of different
      semiconductor materials have multiple bandgaps that allow reducing the relaxation
      energy loss and substantially increase the power-conversion efficiency. The
      choice of materials for each sub-cell is very limited due to the difficulties in
      extracting the current between the layers caused by the requirements for lattice-
      and current-matching. We propose a new vacuum multi-junction solar cell with
      multiple p-n junctions separated by vacuum gaps that allow using different
      semiconductor materials as cathode and anode, both activated to the state of
      effective negative electron affinity (NEA). In this work, the compact proximity
      focused vacuum tube with the GaAs(Cs,O) photocathode and AlGaAs/GaAs-(Cs,O) anode
      with GaAs quantum wells (QWs) is used as a prototype of a vacuum single-junction
      solar cell. The photodiode with the p-AlGaAs/GaAs anode showed the spectral power
      conversion efficiency of about 1% at V bias  = 0 in transmission and reflection
      modes, while, at V bias  = 0.5 V, the efficiency increased up to 10%. In terms of
      energy conservation, we found the condition at which the energy cathode-to-anode
      transition was close to 1. Considering only the energy conservation part, the NEA
      cell power-conversion efficiency can rich a quantum yield value which is measured
      up to more than 50%.

PMID- 29170439
TI  - Body representation disturbances in visual perception and affordance perception
      persist in eating disorder patients after completing treatment.
AB  - Body image disturbances (BID) are a key feature of eating disorders (ED).
      Clinical experience shows that BID exists in patients who Completed their Eating
      Disorder Treatment (CEDT), however studies concerning BID in CEDT patients are
      often limited to cognition and affect, measured by interviews and questionnaires.
      The current study is the first systematic study investigating the full scope of
      the mental body representation, including bodily attitudes, visual perception of
      body size, tactile perception, and affordance perception in CEDT patients. ED
      patients (N = 22), CEDT patients (N = 39) and healthy controls (HC; N = 30) were
      compared on BID tasks including the Body Attitude Test (BAT), Visual Size
      Estimation (VSE), Tactile Estimation Task (TET), and Hoop Task (HT). Results on
      the BAT show higher scores for ED patients compared to CEDT patients and HC but
      no difference between CEDT patients and HC. Both ED and CEDT patients show larger
      overestimations on the VSE and HT compared to HC, where ED patients show the
      largest overestimations. No group differences were found on the TET. The results
      indicate the existence of disturbances in visual perception and affordance
      perception in CEDT patients. Research focussing on more effective treatments for
      ED addressing multiple (sensory) modalities is advised.

PMID- 29170440
TI  - Evidence for unconscious regulation of performance in fatigue.
AB  - Since fatigue is prevalent in modern societies, it is necessary to clarify the
      neural mechanisms of fatigue. The regulation of performance through fatigue
      sensation is one of the mechanisms that decreases performance in fatigue.
      However, it is unknown whether subjective feeling of fatigue is necessary for the
      regulation of performance. Here, we examined whether decreased performance occurs
      without increased fatigue sensation through the experiment which was designed to
      test if fatigue can be learned unconsciously. Healthy male volunteers performed a
      fatigue-inducing hand-grip task for 10 min while viewing a target image presented
      without awareness. On the next day, they viewed a control and the target images
      presented with awareness and the neural activity caused by viewing the images was
      measured using magnetoencephalography. Results showed the level of fatigue
      sensation was not altered but grip-strength was decreased by viewing the target
      image on the second day. The level of beta band power in Brodmann's area 31 was
      increased by viewing the target image and this increase was negatively associated
      with the decrease of grip-strength caused in the hand-grip task. These findings
      demonstrated that fatigue can be learned unconsciously and that there is a
      mechanism to decrease performance without fatigue sensation.

PMID- 29170441
TI  - Genome-wide identification and differential analysis of translational initiation.
AB  - Translation is principally regulated at the initiation stage. The development of
      the translation initiation (TI) sequencing (TI-seq) technique has enabled the
      global mapping of TIs and revealed unanticipated complex translational landscapes
      in metazoans. Despite the wide adoption of TI-seq, there is no computational tool
      currently available for analyzing TI-seq data. To fill this gap, we develop a
      comprehensive toolkit named Ribo-TISH, which allows for detecting and
      quantitatively comparing TIs across conditions from TI-seq data. Ribo-TISH can
      also predict novel open reading frames (ORFs) from regular ribosome profiling
      (rRibo-seq) data and outperform several established methods in both computational
      efficiency and prediction accuracy. Applied to published TI-seq/rRibo-seq data
      sets, Ribo-TISH uncovers a novel signature of elevated mitochondrial translation
      during amino-acid deprivation and predicts novel ORFs in 5'UTRs, long noncoding
      RNAs, and introns. These successful applications demonstrate the power of Ribo
      TISH in extracting biological insights from TI-seq/rRibo-seq data.

PMID- 29170442
TI  - Inhibition of the inflammatory response to stress by targeting interaction
      between PKR and its cellular activator PACT.
AB  - PKR is a cellular kinase involved in the regulation of the integrative stress
      response (ISR) and pro-inflammatory pathways. Two N-terminal dsRNA Binding
      Domains (DRBD) are required for activation of PKR, by interaction with either
      dsRNA or PACT, another cellular DRBD-containing protein. A role for PKR and PACT
      in inflammatory processes linked to neurodegenerative diseases has been proposed
      and raised interest for pharmacological PKR inhibitors. However, the role of PKR
      in inflammation is subject to controversy. We identified the flavonoid luteolin
      as an inhibitor of the PKR/PACT interaction at the level of their DRBDs using
      high-throughput screening of chemical libraries by homogeneous time-resolved
      fluorescence. This was further validated using NanoLuc-Based Protein
      Complementation Assay. Luteolin inhibits PKR phosphorylation, the ISR and the
      induction of pro-inflammatory cytokines in human THP1 macrophages submitted to
      oxidative stress and toll-like receptor (TLR) agonist. Similarly, luteolin
      inhibits induction of pro-inflammatory cytokines in murine microglial
      macrophages. In contrast, luteolin increased activation of the inflammasome, in a
      PKR-independent manner. Collectively, these data delineate the importance of PKR
      in the inflammation process to the ISR and induction of pro-inflammatory
      cytokines. Pharmacological inhibitors of PKR should be used in combination with
      drugs targeting directly the inflammasome.

PMID- 29170444
TI  - Enhanced strength and ductility in a friction stir processing engineered dual
      phase high entropy alloy.
AB  - The potential of high-entropy alloys (HEAs) to exhibit an extraordinary
      combination of properties by shifting the compositional regime from the corners
      towards the centers of phase diagrams has led to worldwide attention by material
      scientists. Here we present a strong and ductile non-equiatomic HEA obtained
      after friction stir processing (FSP). A transformation-induced plasticity (TRIP)
      assisted HEA with composition Fe50Mn30Co10Cr10 (at.%) was severely deformed by
      FSP and evaluated for its microstructure-mechanical property relationship. The
      FSP-engineered microstructure of the TRIP HEA exhibited a substantially smaller
      grain size, and optimized fractions of face-centered cubic (f.c.c., gamma) and
      hexagonal close-packed (h.c.p., epsilon) phases, as compared to the as
      homogenized reference material. This results in synergistic strengthening via
      TRIP, grain boundary strengthening, and effective strain partitioning between the
      gamma and epsilon phases during deformation, thus leading to enhanced strength
      and ductility of the TRIP-assisted dual-phase HEA engineered via FSP.

PMID- 29170443
TI  - Should we screen for the sexually-transmitted infection Mycoplasma genitalium?
      Evidence synthesis using a transmission-dynamic model.
AB  - There is increasing concern about Mycoplasma genitalium as a cause of urethritis,
      cervicitis, pelvic inflammatory disease (PID), infertility and ectopic pregnancy.
      Commercial nucleic acid amplification tests (NAATs) are becoming available, and
      their use in screening for M. genitalium has been advocated, but M. genitalium's
      natural history is poorly-understood, making screening's effectiveness unclear.
      We used a transmission-dynamic compartmental model to synthesise evidence from
      surveillance data and epidemiological and behavioural studies to better
      understand M. genitalium's natural history, and then examined the effects of
      implementing NAAT testing. Introducing NAAT testing initially increases
      diagnoses, by finding a larger proportion of infections; subsequently the
      diagnosis rate falls, due to reduced incidence. Testing only symptomatic patients
      finds relatively little infection in women, as a large proportion is
      asymptomatic. Testing both symptomatic and asymptomatic patients has a much
      larger impact and reduces cumulative PID incidence in women due to M. genitalium
      by 31.1% (95% range:13.0%-52.0%) over 20 years. However, there is important
      uncertainty in M. genitalium's natural history parameters, leading to uncertainty
      in the absolute reduction in PID and sequelae. Empirical work is required to
      improve understanding of key aspects of M. genitalium's natural history before it
      will be possible to determine the effectiveness of screening.

PMID- 29170445
TI  - A novel bi-domain plant defensin MtDef5 with potent broad-spectrum antifungal
      activity binds to multiple phospholipids and forms oligomers.
AB  - Defensins are cysteine-rich cationic antimicrobial peptides contributing to the
      innate immunity in plants. A unique gene encoding a highly cationic bi-domain
      defensin MtDef5 has been identified in a model legume Medicago truncatula. MtDef5
      consists of two defensin domains of 50 amino acids each linked by a 7-amino acid
      peptide. It exhibits broad-spectrum antifungal activity against filamentous fungi
      at submicromolar concentrations. It rapidly permeabilizes the plasma membrane of
      the ascomycete fungi Fusarium graminearum and Neurospora crassa and induces
      accumulation of reactive oxygen species. It is internalized by these fungi, but
      uses spatially distinct modes of entry into these fungi. It co-localizes with
      cellular membranes, travels to nucleus and becomes dispersed in other subcellular
      locations. It binds to several membrane-resident phospholipids with preference
      for phosphatidylinositol monophosphates and forms oligomers. Mutations of the
      cationic amino acids present in the two gamma-core motifs of this defensin that
      eliminate oligomerization also knockout its ability to induce membrane
      permeabilization and fungal growth arrest. MtDef5 is the first bi-domain plant
      defensin that exhibits potent broad-spectrum antifungal activity, recruits
      multiple membrane phospholipids and forms oligomers in their presence. These
      findings raise the possibility that MtDef5 might be useful as a novel antifungal
      agent in transgenic crops.

PMID- 29170446
TI  - Radiographic assessment of the skeletons of Dolly and other clones finds no
      abnormal osteoarthritis.
AB  - Our recent report detailing the health status of cloned sheep concluded that the
      animals had aged normally. This is in stark contrast to reports on Dolly (first
      animal cloned from adult cells) whose diagnoses of osteoarthritis (OA) at 51/2
      years of age led to considerable scientific concern and media debate over the
      possibility of early-onset age-related diseases in cloned animals. Our study
      included four 8-year old ewes derived from the cell line that gave rise to Dolly,
      yet none of our aged sheep showed clinical signs of OA, and they had radiographic
      evidence of only mild or, in one case, moderate OA. Given that the only formal
      record of OA in Dolly is a brief mention of a single joint in a conference
      abstract, this led us to question whether the original concerns about Dolly's OA
      were justified. As none of the original clinical or radiographic records were
      preserved, we undertook radiographic examination of the skeletons of Dolly and
      her contemporary clones. We report a prevalence and distribution of radiographic
      OA similar to that observed in naturally conceived sheep, and our healthy aged
      cloned sheep. We conclude that the original concerns that cloning had caused
      early-onset OA in Dolly were unfounded.

PMID- 29170447
TI  - Monocyte-derived exosomes upon exposure to cigarette smoke condensate alter their
      characteristics and show protective effect against cytotoxicity and HIV-1
      replication.
AB  - Smoking is known to exacerbate HIV-1 pathogenesis, especially in monocytes,
      through the oxidative stress pathway. Exosomes are known to alter HIV-1
      pathogenesis through inter-cellular communication. However, the role of exosomes
      in smoking-mediated HIV-1 pathogenesis is unknown. In this study, we investigated
      the effect of cigarette smoke condensate (CSC) on the characteristics of monocyte
      derived exosomes and their influence on HIV-1 replication. Initially, we
      demonstrated that CSC reduced total protein and antioxidant capacity in exosomes
      derived from HIV-1-infected and uninfected macrophages. The exosomes from CSC
      treated uninfected cells showed a protective effect against cytotoxicity and
      viral replication in HIV-1-infected macrophages. However, exosomes derived from
      HIV-1-infected cells lost their protective capacity. The results suggest that the
      exosomal defense is likely to be more effective during the early phase of HIV-1
      infection and diminishes at the latter phase. Furthermore, we showed CSC-mediated
      upregulation of catalase in exosomes from uninfected cells, with a decrease in
      the levels of catalase and PRDX6 in exosomes derived from HIV-1-infected cells.
      These results suggest a potential role of antioxidant enzymes, which are
      differentially packaged into CSC-exposed HIV-1-infected and uninfected cell
      derived exosomes, on HIV-1 replication of recipient cells. Overall, our study
      suggests a novel role of exosomes in tobacco-mediated HIV-1 pathogenesis.

PMID- 29170448
TI  - Colorectal cancer screening in patients with spinal cord injury yields similar
      results to the general population with an effective bowel preparation: a
      retrospective chart audit.
AB  - STUDY DESIGN: Retrospective chart audit. OBJECTIVES: To compare adequacy of
      colonoscopy bowel preparation and diagnostic findings between persons with SCI
      receiving an extended inpatient bowel preparation and the general population.
      SETTING: Veterans Affairs Puget Sound Healthcare System, Seattle, WA, USA.
      METHODS: We reviewed an electronic database of all colonoscopies performed at a
      tertiary Veterans Affairs medical center between 7/12/13 and 15/10/15. Patients
      with SCI received a multi-day bowel preparation with magnesium citrate, and 8-10
      liters of polyethylene glycol-3350 and electrolyte colonic lavage solution (PEG
      ELS) over two and one half days. The control population received a standard bowel
      preparation consisting of magnesium citrate and 4 liters of PEG-ELS over 1 day.
      RESULTS: Two hundred and fifty-five patients were included in the study,
      including 85 patients with SCI. Average risk screening was a more common
      colonoscopy indication in patients with SCI vs. the control population (24 vs.
      13% p = 0.03). There was no difference in adequacy of bowel preparation (87 vs.
      85%, p = 0.73) or adenoma detection rate (55 vs. 51%, p = 0.59) when comparing
      patients with SCI with the control population. No difference in polyp
      histopathology was detected (p = 0.748). CONCLUSIONS: Our study demonstrated that
      an extended bowel preparation for patients with SCI produces similar bowel
      preparation results and diagnostic yield when compared to patients without SCI
      undergoing colonoscopy.

PMID- 29170449
TI  - Quantitative analysis of biofluid spots by coated blade spray mass spectrometry,
      a new approach to rapid screening.
AB  - This study demonstrates the quantitative capabilities of coated blade spray (CBS)
      mass spectrometry (MS) for the concomitant analysis of multiple target substances
      in biofluid spots. In CBS-MS the analytes present in a given sample are first
      isolated and enriched in the thin coating of the CBS device. After a quick
      rinsing of the blade surface, as to remove remaining matrix, the analytes are
      quickly desorbed with the help of a solvent and then directly electrosprayed into
      the MS analyzer. Diverse pain management drugs, controlled substances, and
      therapeutic medications were successfully determined using only 10 uL of
      biofluid, with limits of quantitation in the low/sub ng.mL-1 level attained
      within 7 minutes.

PMID- 29170451
TI  - Chemokines protect vascular smooth muscle cells from cell death induced by cyclic
      mechanical stretch.
AB  - The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs)
      in the vessel wall to cyclic mechanical stretch (CMS), which evokes VSMC
      proliferation, cell death, phenotypic switching, and migration, leading to
      vascular remodeling. These responses have been observed in many cardiovascular
      diseases; however, the underlying mechanisms remain unclear. We have revealed
      that CMS of rat aortic smooth muscle cells (RASMCs) causes JNK- and p38-dependent
      cell death and that a calcium channel blocker and angiotensin II receptor
      antagonist decreased the phosphorylation of JNK and p38 and subsequently
      decreased cell death by CMS. In the present study, we showed that the expression
      of Cxcl1 and Cx3cl1 was induced by CMS in a JNK-dependent manner. The expression
      of Cxcl1 was also induced in VSMCs by hypertension produced by abdominal aortic
      constriction (AAC). In addition, antagonists against the receptors for CXCL1 and
      CX3CL1 increased cell death, indicating that CXCL1 and CX3CL1 protect RASMCs from
      CMS-induced cell death. We also revealed that STAT1 is activated in RASMCs
      subjected to CMS. Taken together, these results indicate that CMS of VSMCs
      induces inflammation-related gene expression, including that of CXCL1 and CX3CL1,
      which may play important roles in the stress response against CMS caused by
      hypertension.

PMID- 29170450
TI  - Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous
      cell carcinoma.
AB  - Notch1 transactivates Notch3 to drive terminal differentiation in stratified
      squamous epithelia. Notch1 and other Notch receptor paralogs cooperate to act as
      a tumor suppressor in squamous cell carcinomas (SCCs). However, Notch1 can be
      stochastically activated to promote carcinogenesis in murine models of SCC.
      Activated form of Notch1 promotes xenograft tumor growth when expressed
      ectopically. Here, we demonstrate that Notch1 activation and epithelial
      mesenchymal transition (EMT) are coupled to promote SCC tumor initiation in
      concert with transforming growth factor (TGF)-beta present in the tumor
      microenvironment. We find that TGFbeta activates the transcription factor ZEB1 to
      repress Notch3, thereby limiting terminal differentiation. Concurrently, TGFbeta
      drives Notch1-mediated EMT to generate tumor initiating cells characterized by
      high CD44 expression. Moreover, Notch1 is activated in a small subset of SCC
      cells at the invasive tumor front and predicts for poor prognosis of esophageal
      SCC, shedding light upon the tumor promoting oncogenic aspect of Notch1 in SCC.

PMID- 29170453
TI  - Association of protein kinase CK2 inhibition with cellular radiosensitivity of
      non-small cell lung cancer.
AB  - Protein kinase CK2 is a highly conserved protein Ser/Thr protein kinase and plays
      important roles in cell proliferation, protein translation and cell survival.
      This study investigated the possibility of using CK2 inhibition as a new approach
      for increasing the efficacy of radiotherapy in non-small cell lung cancer (NSCLC)
      and its underlying mechanisms. Kinase inhibition of CK2 was attempted either by
      using the specific CK2 inhibitor, Quinalizarin or by applying siRNA interference
      technology to silence the expression of the catalytic subunit of CK2 in A549 and
      H460 cells. The results showed that CK2alpha knockdown or Quinalizarin
      significantly enhanced the radiosensitivity of various NSCLC cells. The notable
      findings we observed after exposure to both CK2 inhibition and ionizing radiation
      (IR) were a prolonged delay in radiation-induced DNA double-strand breaks (DSB)
      repair, robust G2/M checkpoint arrest and increased apoptosis. In vivo studies
      further demonstrated that compared with each treatment alone, CK2 inhibition
      combined with IR reduced tumor growth in the H460 cell xenograft model. In
      conclusion, CK2 is a promising target for the enhancement of radiosensitivity in
      NSCLC.

PMID- 29170452
TI  - Liraglutide restores chronic ER stress, autophagy impairments and apoptotic
      signalling in SH-SY5Y cells.
AB  - Growing evidence suggests that agonists of glucagon-like peptide (GLP-1) receptor
      exert neuroprotective and neurorestorative effects across a range of experimental
      models of neuronal degeneration, and, recently, a pilot clinical trial of
      Liraglutide in Alzheimer's disease patients showed improvements in cerebral
      glucose consumption that signifies disease progression. However, the exact
      underlying mechanism of action remains unclear. Chronic endoplasmic reticulum
      (ER) stress has recently emerged as a mechanism for neuronal injury, rendering it
      a potent therapeutic target for acute and chronic neurodegenerative disorders.
      Here, we investigate the neuroprotective effects of Liraglutide along with the
      signalling network against prolong ER stress and autophagy impairments induced by
      the non-competitive inhibitor of sarco/ER Ca2+-ATPase, thapsigargin. We show that
      Liraglutide modulates the ER stress response and elicits ER proteostasis and
      autophagy machinery homeostasis in human SH-SY5Y neuroblastoma cell line. These
      effects correlate with resolution of hyper-activity of the antioxidant Nrf2
      factor and restoration of the impaired cell viability and proliferation.
      Mechanistically, Liraglutide engages Akt and signal transducer and activator of
      transcription 3 (STAT3) signalling to favour adaptive responses and shift cell
      fate from apoptosis to survival under chronic stress conditions in SH-SY5Y cells.

PMID- 29170454
TI  - CB2 receptor activation causes an ERK1/2-dependent inflammatory response in human
      RPE cells.
AB  - A chronic low-level inflammation contributes to the pathogenesis of age-related
      macular degeneration (AMD), the most common cause of blindness in the elderly in
      Western countries. The loss of central vision results from attenuated maintenance
      of photoreceptors due to the degeneration of retinal pigment epithelium (RPE)
      cells beneath the photoreceptor layer. It has been proposed that pathologic
      inflammation initiated in RPE cells could be regulated by the activation of type
      2 cannabinoid receptors (CB2). Here, we have analysed the effect of CB2
      activation on cellular survival and inflammation in human RPE cells. RPE cells
      were treated with the selective CB2 agonist JWH-133 in the presence or absence of
      the oxidative stressor 4-hydroxynonenal. Thereafter, cellular viability as well
      as the release of pro-inflammatory cytokines and potential underlying signalling
      pathways were analysed. Our results show that JWH-133 led to increased
      intracellular Ca2+ levels, suggesting that RPE cells are capable of responding to
      a CB2 agonist. JWH-133 could not prevent oxidative stress-induced cell death.
      Instead, 10 uM JWH-133 increased cell death and the release of proinflammatory
      cytokines in an ERK1/2-dependent manner. In contrast to previous findings, CB2
      activation increased, rather than reduced inflammation in RPE cells.

PMID- 29170455
TI  - Ultrafast bridge planarization in donor-pi-acceptor copolymers drives
      intramolecular charge transfer.
AB  - Donor-pi-acceptor conjugated polymers form the material basis for high power
      conversion efficiencies in organic solar cells. Large dipole moment change upon
      photoexcitation via intramolecular charge transfer in donor-pi-acceptor backbone
      is conjectured to facilitate efficient charge-carrier generation. However, the
      primary structural changes that drive ultrafast charge transfer step have
      remained elusive thereby limiting a rational structure-function correlation for
      such copolymers. Here we use structure-sensitive femtosecond stimulated Raman
      spectroscopy to demonstrate that pi-bridge torsion forms the primary reaction
      coordinate for intramolecular charge transfer in donor-pi-acceptor copolymers.
      Resonance-selective Raman snapshots of exciton relaxation reveal rich vibrational
      dynamics of the bridge modes associated with backbone planarization within 400
      fs, leading to hot intramolecular charge transfer state formation while
      subsequent cooling dynamics of backbone-centric modes probe the charge transfer
      relaxation. Our work establishes a phenomenological gating role of bridge
      torsions in determining the fundamental timescale and energy of photogenerated
      carriers, and therefore opens up dynamics-based guidelines for fabricating energy
      efficient organic photovoltaics.

PMID- 29170456
TI  - Determination of Asphaltene Critical Nanoaggregate Concentration Region Using
      Ultrasound Velocity Measurements.
AB  - Asphaltenes constitute the heaviest, most polar and aromatic fraction of
      petroleum crucial to the formation of highly-stable water-in-crude oil emulsions.
      The latter occur during crude oil production as well as spills and cause
      difficulties to efficient remediation practice. It is thought that in
      nanoaggregate form, asphaltenes create elastic layers around water droplets
      enhancing stability of the emulsion matrix. Ultrasonic characterisation is a high
      resolution non-invasive tool in colloidal analysis shown to successfully identify
      asphaltene nanoaggregation in toluene. The high sensitivity of acoustic velocity
      to molecular rearrangements and ease in implementation renders it an attractive
      method to study asphaltene phase properties. Currently, aggregation is thought to
      correspond to an intersection of two concentration-ultrasonic velocity
      regressions. Our measurements indicate a variation in the proximity of
      nanoaggregation which is not accounted for by present models. We attribute this
      uncertainty to physico-chemical heterogeneity of the asphaltene fraction driven
      by variation in molecular size and propose a critical nanoaggregation region. We
      treated asphaltenes from North and South American crude oils with ruthenium ion
      catalysed oxidation to characterize their n-alkyl appendages attached to aromatic
      cores. Principal component analysis was performed to investigate the coupling
      between asphaltene structures and velocity measurements and their impact on
      aggregation.

PMID- 29170457
TI  - Pulsed Corona Discharge Induced Hydroxyl Radical Transfer Through the Gas-Liquid
      Interface.
AB  - The highly energetic electrons in non-thermal plasma generated by gas phase
      pulsed corona discharge (PCD) produce hydroxyl (OH) radicals via collision
      reactions with water molecules. Previous work has established that OH radicals
      are formed at the plasma-liquid interface, making it an important location for
      the oxidation of aqueous pollutants. Here, by contacting water as aerosol with
      PCD plasma, it is shown that OH radicals are produced on the gas side of the
      interface, and not in the liquid phase. It is also demonstrated that the gas
      liquid interfacial boundary poses a barrier for the OH radicals, one they need to
      cross for reactive affinity with dissolved components, and that this process
      requires a gaseous atomic H scavenger. For gaseous oxidation, a scavenger, oxygen
      in common cases, is an advantage but not a requirement. OH radical efficiency in
      liquid phase reactions is strongly temperature dependent as radical termination
      reaction rates increase with temperature.

PMID- 29170458
TI  - Towards personalised allele-specific CRISPR gene editing to treat autosomal
      dominant disorders.
AB  - CRISPR/Cas9 holds immense potential to treat a range of genetic disorders. Allele
      specific gene disruption induced by non-homologous end-joining (NHEJ) DNA repair
      offers a potential treatment option for autosomal dominant disease. Here, we
      successfully delivered a plasmid encoding S. pyogenes Cas9 and sgRNA to the
      corneal epithelium by intrastromal injection and acheived long-term knockdown of
      a corneal epithelial reporter gene, demonstrating gene disruption via NHEJ in
      vivo. In addition, we used TGFBI corneal dystrophies as a model of autosomal
      dominant disease to assess the use of CRISPR/Cas9 in two allele-specific systems,
      comparing cleavage using a SNP-derived PAM to a guide specific approach. In
      vitro, cleavage via a SNP-derived PAM was found to confer stringent allele
      specific cleavage, while a guide-specific approach lacked the ability to
      distinguish between the wild-type and mutant alleles. The failings of the guide
      specific approach highlights the necessity for meticulous guide design and
      assessment, as various degrees of allele-specificity are achieved depending on
      the guide sequence employed. A major concern for the use of CRISPR/Cas9 is its
      tendency to cleave DNA non-specifically at "off-target" sites. Confirmation that
      S. pyogenes Cas9 lacks the specificity to discriminate between alleles differing
      by a single base-pair regardless of the position in the guide is demonstrated.

PMID- 29170459
TI  - Randomness-induced quantum spin liquid on honeycomb lattice.
AB  - Quantum entanglement in magnetic materials is expected to yield a quantum spin
      liquid (QSL), in which strong quantum fluctuations prevent magnetic ordering even
      at zero temperature. This topic has been one of the primary focuses of condensed
      matter science since Anderson first proposed the resonating valence bond state in
      a certain spin-1/2 frustrated magnet in 1973. Since then, several candidate
      materials featuring frustration, such as triangular and kagome lattices, have
      been reported to exhibit liquid-like behavior. However, the mechanisms that
      stabilize the liquid-like states have remained elusive. Here, we present a QSL
      state in a spin-1/2 honeycomb lattice with randomness in the exchange
      interaction. That is, we successfully introduce randomness into the organic
      radial-based complex and realize a random-singlet (RS) state (or valence bond
      glass). All magnetic and thermodynamic experimental results indicate the liquid
      like behaviors, which are consistent with those expected in the RS state. Our
      results suggest that the randomness or inhomogeneity in the actual systems
      stabilize the RS state and yield liquid-like behavior.

PMID- 29170460
TI  - Different diversity-dependent declines in speciation rate unbalances species
      richness in terrestrial slugs.
AB  - Two genera of terrestrial slugs (Arion and Geomalacus) display a striking
      disproportion in species richness in the Iberian Peninsula. While there are 17
      Iberian endemic species in Arion, morphological criteria only recognize four
      species within Geomalacus. Sequence data were used to test whether these
      differences could result from: (1) cryptic diversity within Geomalacus; (2) an
      earlier origin for Arion (older clades are expected to accumulate more species);
      (3) distinct patterns of diversification rates (higher initial speciation rates
      in Arion), and (4) some combination of the above factors (e.g., an older clade
      with higher speciation rates). Species delimitation tests based on mitochondrial
      and nuclear data revealed eight cryptic lineages within Geomalacus that lessened
      the asymmetry; nevertheless, the disparity required further investigation. No
      meaningful differences in crown group ages of each recovered clade were found.
      Regardless the different premises of the two equally plausible diversification
      models (similar initial speciation rates vs. higher initial speciation rates in
      Geomalacus), both coincide on diversity-dependent diversification for the two
      groups but weaker rate declines in Arion best explains the observed asymmetry in
      species richness. Also, the broader environmental tolerance combined with a
      faster dispersal and wider distribution may have represented an evolutionary
      advantage for Arion.

PMID- 29170461
TI  - Beliefs about Others' Abilities Alter Learning from Observation.
AB  - Learning what is dangerous by observing others can be safer and more efficient
      than individual learning. The efficiency of observational learning depends on how
      observational information is used, something we propose depends on our beliefs'
      about others. Here, we investigated how described and actual abilities of another
      individual (a demonstrator) influenced performance and psychophysiology during
      learning of an observational avoidance task. Participants were divided into two
      groups. In each group there were two demonstrators who were described as either
      high (Described-High group) or low (Described-Low group) in their ability to
      learn the task. In both groups, one demonstrator had a high ability (Actual-High)
      and the other had a low ability (Actual-Low) to learn. Participants performed
      worse in the Described-Low compared to the Described-High group. Pupil dilation,
      and behavioral data in combination with reinforcement learning modeling,
      suggested that the described ability influenced performance by affecting the
      level of attention towards the observational information. Skin conductance
      responses and pupil dilation provided us with a separate measure of learning in
      addition to choice behavior.

PMID- 29170463
TI  - Associating a product with a luxury brand label modulates neural reward
      processing and favors choices in materialistic individuals.
AB  - The present study investigated the extent to which luxury vs. non-luxury brand
      labels (i.e., extrinsic cues) randomly assigned to items and preferences for
      these items impact choice, and how this impact may be moderated by materialistic
      tendencies (i.e., individual characteristics). The main objective was to
      investigate the neural correlates of abovementioned effects using functional
      magnetic resonance imaging. Behavioural results showed that the more
      materialistic people are, the more they choose and like items labelled with
      luxury brands. Neuroimaging results revealed the implication of a neural network
      including the dorsolateral and ventromedial prefrontal cortex and the
      orbitofrontal cortex that was modulated by the brand label and also by the
      participants' preference. Most importantly, items with randomly assigned
      luxurious brand labels were preferentially chosen by participants and triggered
      enhanced signal in the caudate nucleus. This effect increased linearly with
      materialistic tendencies. Our results highlight the impact of brand-item
      association, although random in our study, and materialism on preference, relying
      on subparts of the brain valuation system for the integration of extrinsic cues,
      preferences and individual characteristics.

PMID- 29170464
TI  - Giant Anisotropic Magnetocaloric Effect in Double-perovskite Gd2CoMnO6 Single
      Crystals.
AB  - The magnetocaloric effect (MCE) is described by the change in temperature of a
      material by magnetic field variation and is a crucial subject in magnetism; it is
      motivated by the desire to enhance energy-efficient magnetic refrigeration for
      clean technology. Despite the recent discovery of the giant cryogenic MCE in
      double perovskites, the role of magnetic anisotropy has not yet been clearly
      discussed, because of the averaging effect of polycrystalline samples. Here, we
      investigated the anisotropic MCE in the single-crystal double perovskite
      Gd2CoMnO6. In addition to the ferromagnetic order of the Co2+ and Mn4+ moments,
      the large Gd3+ moments align below T Gd = 21 K, exhibiting an isotropic nature.
      Because of the intricate temperature development of magnetically hysteretic
      behaviour and metamagnetism, the change in magnetic entropy along the c-axis
      appears to be relatively small. On the contrary, the smaller but almost
      reversible magnetization perpendicular to the c-axis leads to a large MCE with a
      maximum entropy change of 25.4 J/kg.K. The anisotropic MCE generates a giant
      rotational MCE, estimated as 16.6 J/kg.K. Our results demonstrate the importance
      of magnetic anisotropy for understanding the MCE and reveal essential clues for
      exploring suitable magnetic refrigerant compounds aiming at magnetic functional
      applications.

PMID- 29170462
TI  - Structure of Rap1b bound to talin reveals a pathway for triggering integrin
      activation.
AB  - Activation of transmembrane receptor integrin by talin is essential for inducing
      cell adhesion. However, the pathway that recruits talin to the membrane, which
      critically controls talin's action, remains elusive. Membrane-anchored mammalian
      small GTPase Rap1 is known to bind talin-F0 domain but the binding was shown to
      be weak and thus hardly studied. Here we show structurally that talin-F0 binds to
      human Rap1b like canonical Rap1 effectors despite little sequence homology, and
      disruption of the binding strongly impairs integrin activation, cell adhesion,
      and cell spreading. Furthermore, while being weak in conventional binary binding
      conditions, the Rap1b/talin interaction becomes strong upon attachment of
      activated Rap1b to vesicular membranes that mimic the agonist-induced
      microenvironment. These data identify a crucial Rap1-mediated membrane-targeting
      mechanism for talin to activate integrin. They further broadly caution the
      analyses of weak protein-protein interactions that may be pivotal for function
      but neglected in the absence of specific cellular microenvironments.

PMID- 29170465
TI  - Egr1 deficiency induces browning of inguinal subcutaneous white adipose tissue in
      mice.
AB  - Beige adipocyte differentiation within white adipose tissue, referred to as
      browning, is seen as a possible mechanism for increasing energy expenditure. The
      molecular regulation underlying the thermogenic browning process has not been
      entirely elucidated. Here, we identify the zinc finger transcription factor EGR1
      as a negative regulator of the beige fat program. Loss of Egr1 in mice promotes
      browning in the absence of external stimulation and leads to an increase of Ucp1
      expression, which encodes the key thermogenic mitochondrial uncoupling protein-1.
      Moreover, EGR1 is recruited to the proximal region of the Ucp1 promoter in
      subcutaneous inguinal white adipose tissue. Transcriptomic analysis of
      subcutaneous inguinal white adipose tissue in the absence of Egr1 identifies the
      molecular signature of white adipocyte browning downstream of Egr1 deletion and
      highlights a concomitant increase of beige differentiation marker and a decrease
      in extracellular matrix gene expression. Conversely, Egr1 overexpression in
      mesenchymal stem cells decreases beige adipocyte differentiation, while
      increasing extracellular matrix production. These results reveal a role for Egr1
      in blocking energy expenditure via direct Ucp1 transcription repression and
      highlight Egr1 as a therapeutic target for counteracting obesity.

PMID- 29170466
TI  - Statistics and simulation of growth of single bacterial cells: illustrations with
      B. subtilis and E. coli.
AB  - The inherent stochasticity of molecular reactions prevents us from predicting the
      exact state of single-cells in a population. However, when a population grows at
      steady-state, the probability to observe a cell with particular combinations of
      properties is fixed. Here we validate and exploit existing theory on the
      statistics of single-cell growth in order to predict the probability of
      phenotypic characteristics such as cell-cycle times, volumes, accuracy of
      division and cell-age distributions, using real-time imaging data for Bacillus
      subtilis and Escherichia coli. Our results show that single-cell growth
      statistics can accurately be predicted from a few basic measurements. These
      equations relate different phenotypic characteristics, and can therefore be used
      in consistency tests of experimental single-cell growth data and prediction of
      single-cell statistics. We also exploit these statistical relations in the
      development of a fast stochastic-simulation algorithm of single-cell growth and
      protein expression. This algorithm greatly reduces computational burden, by
      recovering the statistics of growing cell-populations from the simulation of only
      one of its lineages. Our approach is validated by comparison of simulations and
      experimental data. This work illustrates a methodology for the prediction,
      analysis and tests of consistency of single-cell growth and protein expression
      data from a few basic statistical principles.

PMID- 29170467
TI  - mTORC1 suppresses PIM3 expression via miR-33 encoded by the SREBP loci.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of
      cell growth that is often aberrantly activated in cancer. However, mTORC1
      inhibitors, such as rapamycin, have limited effectiveness as single agent cancer
      therapies, with feedback mechanisms inherent to the signaling network thought to
      diminish the anti-tumor effects of mTORC1 inhibition. Here, we identify the
      protein kinase and proto-oncogene PIM3 as being repressed downstream of mTORC1
      signaling. PIM3 expression is suppressed in cells with loss of the tuberous
      sclerosis complex (TSC) tumor suppressors, which exhibit growth factor
      independent activation of mTORC1, and in the mouse liver upon feeding-induced
      activation of mTORC1. Inhibition of mTORC1 with rapamycin induces PIM3 transcript
      and protein levels in a variety of settings. Suppression of PIM3 involves the
      sterol regulatory element-binding (SREBP) transcription factors SREBP1 and 2,
      whose activation and mRNA expression are stimulated by mTORC1 signaling. We find
      that PIM3 repression is mediated by miR-33, an intronic microRNA encoded within
      the SREBP loci, the expression of which is decreased with rapamycin. These
      results demonstrate that PIM3 is induced upon mTORC1 inhibition, with potential
      implications for the effects of mTORC1 inhibitors in TSC, cancers, and the many
      other disease settings influenced by aberrant mTORC1 signaling.

PMID- 29170468
TI  - Non-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal
      Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI.
AB  - The placenta is a vital organ for fetal growth and development during pregnancy.
      Congenital heart disease (CHD) is a leading cause of morbidity and mortality in
      newborns. Despite the parallel development of the placenta and fetal heart early
      in pregnancy, very few studies suggested an association between placental
      dysfunction and fetal CHD. In this study, we report placental perfusion of
      healthy pregnancies and pregnancies complicated by fetal CHD measured using
      advanced fetal MRI techniques. We studied forty-eight pregnant women (31 healthy
      volunteers and 17 with fetal CHD) that underwent fetal MRI during their second or
      third trimester of pregnancy. Placental perfusion imaging was performed using
      velocity-selective arterial spin labeling (VSASL) and 3D image acquisition with
      whole-placenta coverage. In pregnancies with fetal CHD, global placental
      perfusion significantly decreased and regional variation of placental perfusion
      significantly increased with advancing gestational age; however, no such
      correlation was found in healthy pregnancies. Also, global placental perfusion
      was significantly higher in fetal CHD versus controls, in the lateral side-lying
      patient position versus supine, and in the posterior placental position versus
      anterior placental position. This study reports for the first time non-invasive
      whole-placenta perfusion imaging in utero. These data suggest that placental
      VSASL may serve as a potential biomarker of placental dysfunction in fetuses
      diagnosed with CHD.

PMID- 29170470
TI  - Switchable photovoltaic windows enabled by reversible photothermal complex
      dissociation from methylammonium lead iodide.
AB  - Materials with switchable absorption properties have been widely used for smart
      window applications to reduce energy consumption and enhance occupant comfort in
      buildings. In this work, we combine the benefits of smart windows with energy
      conversion by producing a photovoltaic device with a switchable absorber layer
      that dynamically responds to sunlight. Upon illumination, photothermal heating
      switches the absorber layer-composed of a metal halide perovskite-methylamine
      complex-from a transparent state (68% visible transmittance) to an absorbing,
      photovoltaic colored state (less than 3% visible transmittance) due to
      dissociation of methylamine. After cooling, the methylamine complex is re-formed,
      returning the absorber layer to the transparent state in which the device acts as
      a window to visible light. The thermodynamics of switching and performance of the
      device are described. This work validates a photovoltaic window technology that
      circumvents the fundamental tradeoff between efficient solar conversion and high
      visible light transmittance that limits conventional semitransparent PV window
      designs.

PMID- 29170469
TI  - Rapid changes in Atlantic grey seal milk from birth to weaning - immune factors
      and indicators of metabolic strain.
AB  - True seals have the shortest lactation periods of any group of placental mammal.
      Most are capital breeders that undergo short, intense lactations, during which
      they fast while transferring substantial proportions of their body reserves to
      their pups, which they then abruptly wean. Milk was collected from Atlantic grey
      seals (Halichoerus grypus) periodically from birth until near weaning. Milk
      protein profiles matured within 24 hours or less, indicating the most rapid
      transition from colostrum to mature phase lactation yet observed. There was an
      unexpected persistence of immunoglobulin G almost until weaning, potentially
      indicating prolonged trans-intestinal transfer of IgG. Among components of innate
      immune protection were found fucosyllactose and siallylactose that are thought to
      impede colonisation by pathogens and encourage an appropriate milk-digestive and
      protective gut microbiome. These oligosaccharides decreased from early lactation
      to almost undetectable levels by weaning. Taurine levels were initially high,
      then fell, possibly indicative of taurine dependency in seals, and progressive
      depletion of maternal reserves. Metabolites that signal changes in the mother's
      metabolism of fats, such as nicotinamide and derivatives, rose from virtual
      absence, and acetylcarnitines fell. It is therefore possible that indicators of
      maternal metabolic strain exist that signal the imminence of weaning.

PMID- 29170471
TI  - Steps forward for cancer precision medicine.
AB  - The availability of targeted anticancer drugs and the relative affordability of
      genomic analyses has led to a growing expectation among patients with cancer that
      they can receive personalized treatment based on the genomic signature of their
      tumour. Here, we discuss some of the challenges and steps needed to bring such
      approaches into routine practice.

PMID- 29170472
TI  - Interaction Effects of AFB1 and MC-LR Co-exposure with Polymorphism of Metabolic
      Genes on Liver Damage: focusing on SLCO1B1 and GSTP1.
AB  - AFB1 and MC-LR are two major environmental risk factors for liver damage
      worldwide, especially in warm and humid areas, but there are individual
      differences in health response of the toxin-exposed populations. Therefore, we
      intended to identify the susceptible genes in transport and metabolic process of
      AFB1 and MC-LR and find their effects on liver damage. We selected eight related
      SNPs that may affect liver damage outcomes in AFB1 and MC-LR exposed persons, and
      enrolled 475 cases with liver damage and 475 controls of healthy people in rural
      areas of China. The eight SNPs were genotyped by PCR and restriction fragment
      length polymorphism. We found that SLCO1B1 (T521C) is a risk factor for liver
      damage among people exposed to high AFB1 levels alone or combined with MC-LR, and
      that GSTP1 (A1578G) could indicate the risk of liver damage among those exposed
      to high MC-LR levels alone or combined with high AFB1 levels. However, GSTP1
      (A1578G) could reduce the risk of liver damage in populations exposed to low MC
      LR levels alone or combined with high AFB1 levels. In conclusion, SLCO1B1 (T521C)
      and GSTP1 (A1578G) are susceptible genes for liver damage in humans exposed to
      AFB1 and/or MC-LR in rural areas of China.

PMID- 29170473
TI  - Generation of an osteoblast-based artificial niche that supports in vitro B
      lymphopoiesis.
AB  - B lymphocytes are produced from hematopoietic stem cells (HSCs) through the
      highly ordered process of B lymphopoiesis, which is regulated by a complex
      network of cytokines, chemokines and cell adhesion molecules derived from the
      hematopoietic niche. Primary osteoblasts function as an osteoblastic niche (OBN)
      that supports in vitro B lymphopoiesis. However, there are significant
      limitations to the use of primary osteoblasts, including their relative scarcity
      and the consistency and efficiency of the limited purification and proliferation
      of these cells. Thus, development of a stable osteoblast cell line that can
      function as a biomimetic or artificial OBN is necessary. In this study, we
      developed a stable osteoblastic cell line, designated OBN4, which functions as an
      osteoblast-based artificial niche that supports in vitro B lymphopoiesis. We
      demonstrated that the production of a B220+ cell population from Lineage- (Lin-)
      Sca-1+ c-Kit+ hematopoietic stem and progenitor cells (HSPCs) was increased ~1.7
      fold by OBN4 cells relative to production by primary osteoblasts and OP9 cells in
      coculture experiments. Consistently, OBN4 cells exhibited the highest production
      of B220+ IgM+ cell populations (6.7+/-0.6-13.6+/-0.6%) in an IL-7- and stromal
      cell-derived factor 1-dependent manner, with higher production than primary
      osteoblasts (3.7+/-0.5-6.4+/-0.6%) and OP9 cells (1.8+/-0.6-3.9+/-0.5%). In
      addition, the production of B220+ IgM+ IgD+ cell populations was significantly
      enhanced by OBN4 cells (15.4+/-1.1-18.9+/-3.2%) relative to production by primary
      osteoblasts (9.5+/-0.6-14.6+/-1.6%) and OP9 cells (9.1+/-0.5-10.3+/-1.8%). We
      conclude that OBN4 cells support in vitro B lymphopoiesis of Lin- Sca-1+ c-Kit+
      HSPCs more efficiently than primary osteoblasts or OP9 stromal cells.

PMID- 29170475
TI  - Leukotriene B4 receptor 2 gene polymorphism (rs1950504, Asp196Gly) leads to
      enhanced cell motility under low-dose ligand stimulation.
AB  - Recently, single-nucleotide polymorphisms (SNPs) in G-protein-coupled receptors
      (GPCRs) have been suggested to contribute to physiopathology and therapeutic
      effects. Leukotriene B4 receptor 2 (BLT2), a member of the GPCR family, plays a
      critical role in the pathogenesis of several inflammatory diseases, including
      cancer and asthma. However, no studies on BLT2 SNP effects have been reported to
      date. In this study, we demonstrate that the BLT2 SNP (rs1950504, Asp196Gly), a
      Gly-196 variant of BLT2 (BLT2 D196G), causes enhanced cell motility under low
      dose stimulation of its ligands. In addition, we demonstrated that Akt activation
      and subsequent production of reactive oxygen species (ROS), both of which act
      downstream of BLT2, are also increased by BLT2 D196G in response to low-dose
      ligand stimulation. Furthermore, we observed that the ligand binding affinity of
      BLT2 D196G was enhanced compared with that of BLT2. Through homology modeling
      analysis, it was predicted that BLT2 D196G loses ionic interaction with R197,
      potentially resulting in increased agonist-receptor interaction. To the best of
      our knowledge, this report is the first to describe a SNP study on BLT2 and shows
      that BLT2 D196G enhances ligand sensitivity, thereby increasing cell motility in
      response to low-dose ligand stimulation.

PMID- 29170474
TI  - Are the view of Helicobacter pylori colonized in the oral cavity an illusion?
AB  - Urea breath test (UBT), as a leading preferred non-invasive diagnostic
      technology, but may not be able to detect oral H. pylori. With negative results
      of UBT, the patient may have an oral infection. On the basis of the fact of
      success, eradication rate may increase by 21% in the 95% Cl range after the
      elimination of oral H. pylori, the author believes oral H. pylori does exist and
      the oral cavity is the second colonized site aside its primary site of the
      stomach. H. pylori migrated out of Africa along with its human host circa 60 000
      years ago; they are not lives in stomach only. In this review article, evidence
      established in recent years studies with use more appropriate technology had been
      listed and discussed. The author considers the oral cavity is a black hole for H.
      pylori infection that significant effective on gastroenterology and another
      medical field. The role of the oral cavity as the source of H. pylori infection
      is so controvert in past years. It seems like a human being having a second-time
      face to discover H. pylori in the history.

PMID- 29170476
TI  - Trib2 regulates the pluripotency of embryonic stem cells and enhances
      reprogramming efficiency.
AB  - Embryonic stem (ES) cells are pluripotent cells characterized by self
      renewability and differentiation potential. Induced pluripotent stem (iPS) cells
      are ES cell-equivalent cells derived from somatic cells by the introduction of
      core reprogramming factors. ES and iPS cells are important sources for
      understanding basic biology and for generating therapeutic cells for clinical
      applications. Tribbles homolog 2 (Trib2) functions as a scaffold in signaling
      pathways. However, the relevance of Trib2 to the pluripotency of ES and iPS cells
      is unknown. In the present study, we elucidated the importance of Trib2 in
      maintaining pluripotency in mouse ES cells and in generating iPS cells from
      somatic cells through the reprogramming process. Trib2 expression decreased as ES
      cells differentiated, and Trib2 knockdown in ES cells changed their colony
      morphology while reducing the activity of alkaline phosphatase and the expression
      of the pluripotency marker genes Oct4, Sox2, Nanog and Klf4. Trib2 directly
      interacted with Oct4 and elevated Oct4 promoter activity. During the generation
      of iPS cells, Trib2 knockdown decreased the reprogramming efficiency of mouse
      embryonic fibroblasts, whereas Trib2 overexpression significantly increased their
      reprogramming efficiency. In summary, our results suggest that Trib2 is important
      for maintaining self-renewal in ES cells and for pluripotency induction during
      the reprogramming process.

PMID- 29170477
TI  - Participation of GATA-3 in regulation of bone healing through transcriptional
      upregulation of bcl-xL expression.
AB  - We have previously demonstrated the expression of GATA-DNA-binding protein (GATA)
      3, a transcription factor, in osteoblasts and have verified its function in
      transducing cell survival signaling. This translational study was further
      designed to evaluate the roles of GATA-3 in regulating bone healing and to
      explore its possible mechanisms. A metaphyseal bone defect was created in the
      left femurs of male ICR mice. Analysis by micro-computed topography showed that
      the bone volume, trabecular bone number and trabecular thickness were augmented
      and that the trabecular pattern factor decreased. Interestingly,
      immunohistological analyses showed specific expression of GATA-3 in the defect
      area. In addition, colocalized expression of GATA-3 and alkaline phosphatase was
      observed at the wound site. As the fracture healed, the amounts of phosphorylated
      and non-phosphorylated GATA-3 concurrently increased. Separately, GATA-3 mRNA was
      induced during bone healing, and, levels of Runx2 mRNA and protein were also
      increased. The results of confocal microscopy and co-immunoprecipitation showed
      an association between nuclear GATA-3 and Runx2 in the area of insult. In
      parallel with fracture healing, Bcl-XL mRNA was significantly triggered. A
      bioinformatic search revealed the existence of a GATA-3-specific DNA-binding
      element in the promoter region of the bcl-xL gene. Analysis by chromatin
      immunoprecipitation assays further demonstrated transactivation activity by which
      GATA-3 regulated bcl-xL gene expression. Therefore, this study shows that GATA-3
      participates in the healing of bone fractures via regulating bcl-xL gene
      expression, owing to its association with Runx2. In the clinic, GATA-3 may be
      used as a biomarker for diagnoses/prognoses or as a therapeutic target for bone
      diseases, such as bone fractures.

PMID- 29170478
TI  - Therapeutic inhibition of SGK1 suppresses colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus,
      the development of new therapeutic targets for CRC treatment is urgently needed.
      SGK1 is involved in various cellular activities, and its dysregulation can result
      in multiple cancers. However, little is known about its roles and associated
      molecular mechanisms in CRC. In present study, we found that SGK1 was highly
      expressed in tumor tissues compared with peri-tumor samples from CRC patients. In
      vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell
      proliferation and migration and inhibited cell apoptosis induced by 5
      fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects.
      Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic
      inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover,
      SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in
      colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC
      cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes
      colorectal cancer development via regulation of CRC cell proliferation, migration
      and survival. Inhibition of SGK1 represents a novel strategy for the treatment of
      CRC.

PMID- 29170480
TI  - Cytokines: The inflamed heart.

PMID- 29170479
TI  - Carbon monoxide prevents TNF-alpha-induced eNOS downregulation by inhibiting NF
      kappaB-responsive miR-155-5p biogenesis.
AB  - Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular
      disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial
      dysfunction associated with the downregulation of endothelial NO synthesis in
      human endothelial cells stimulated with TNF-alpha. Here, we found that the CO
      releasing compound CORM-2 prevented TNF-alpha-mediated decreases in eNOS
      expression and NO/cGMP production, without affecting eNOS promoter activity, by
      maintaining the functional activity of the eNOS mRNA 3'-untranslated region. By
      contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF
      alpha-stimulated endothelial cells, resulting in recovery of the 3'-UTR activity
      of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked
      by an NF-kappaB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against
      HO-1, indicating that CO rescues TNF-alpha-induced eNOS downregulation through NF
      kappaB-responsive miR-155-5p expression via HO-1 induction; similar protective
      effects of ectopic HO-1 expression and bilirubin were observed in endothelial
      cells treated with TNF-alpha. Moreover, heme degradation products, except iron
      and N-acetylcysteine prevented H2O2-mediated miR-155-5p biogenesis and eNOS
      downregulation. These data demonstrate that CO prevents TNF-alpha-mediated eNOS
      downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a
      positive forward circuit between CO and HO-1 induction. This circuit may play an
      important preventive role in inflammatory endothelial dysfunction associated with
      human vascular diseases.

PMID- 29170481
TI  - Globular Shaped Polypyrrole Doped Well-Dispersed Functionalized Multiwall Carbon
      Nanotubes/Nafion Composite for Enzymatic Glucose Biosensor Application.
AB  - Herein, we report preparation of a bio-nanohybrid material of homogenously
      dispersed functionalized multiwall carbon nanotubes (fMWCNTs) in Nafion (Nf)
      doped with polypyrrole (PPy) and followed by one-step in situ electrochemical
      polymerization along with glucose oxidase (GOx) on a platinum (Pt) electrode. The
      bioengineered Nf-GOx-fMWCNTs-PPy/Pt electrode showed excellent electrocatalytic
      performance to detect glucose with a high sensitivity (54.2 MUAmM-1 cm-2) in
      linear range of up to 4.1 mM as well as a low detection limit of 5 MUM (S/N = 3),
      response time within 4 s, good selectivity, stability, and practical
      applicability. It is our hope that the comprehensive results will contribute to
      design an efficient glucose biosensor with practical prospects for biomedical
      applications.

PMID- 29170482
TI  - A New Approach to Deliver Anti-cancer Nanodrugs with Reduced Off-target
      Toxicities and Improved Efficiency by Temporarily Blunting the
      Reticuloendothelial System with Intralipid.
AB  - We have developed a new strategy to temporarily blunt the reticuloendothelial
      system uptake of nanodrugs, a major challenge for nanodrug delivery and causing
      off-target toxicities, using an FDA approved nutrition supplement, Intralipid. We
      have tested our methodology in rats using an experimental platinum-containing
      anti-cancer nanodrug and three FDA approved nanodrugs, Abraxane, Marqibo, and
      Onivyde, to determine their toxicities in liver, spleen, and kidney, with and
      without the addition of Intralipid. Our method illustrates its potentials to
      deliver nanodrugs with an increase in the bioavailability and a decrease in
      toxicities. Our study shows that Intralipid treatment exhibits no harmful effect
      on tumor growing and no negative effect on the anti-tumor efficacy of the
      platinum-containing nanodrug, as well as animal survival rate in a HT-29
      xenograft mouse model. Our methodology could also be a valuable
      complement/supplement to the "stealth" strategies. Our approach is a general one
      applicable to any approved and in-development nanodrugs without additional
      modification of the nanodrugs, thus facilitating its translation to clinical
      settings.

PMID- 29170483
TI  - Free-running Sn precipitates: an efficient phase separation mechanism for
      metastable Ge1-xSnx epilayers.
AB  - The revival of interest in Ge1-xSnx alloys with x >= 10% is mainly owed to the
      recent demonstration of optical gain in this group-IV heterosystem. Yet, Ge and
      Sn are immiscible over about 98% of the composition range, which renders
      epilayers based on this material system inherently metastable. Here, we address
      the temperature stability of pseudomorphic Ge1-xSnx films grown by molecular beam
      epitaxy. Both the growth temperature dependence and the influence of post-growth
      annealing steps were investigated. In either case we observe that the
      decomposition of epilayers with Sn concentrations of around 10% sets in above
      ~230  degrees C, the eutectic temperature of the Ge/Sn system. Time-resolved in
      situ annealing experiments in a scanning electron microscope reveal the crucial
      role of liquid Sn precipitates in this phase separation process. Driven by a
      gradient of the chemical potential, the Sn droplets move on the surface along
      preferential crystallographic directions, thereby taking up Sn and Ge from the
      strained Ge1-xSnx layer. While Sn-uptake increases the volume of the melt, single
      crystalline Ge becomes re-deposited by a liquid-phase epitaxial process at the
      trailing edge of the droplet. This process makes phase separation of metastable
      GeSn layers particularly efficient at rather low temperatures.

PMID- 29170484
TI  - The evaluation of contralateral foot circulation after unilateral
      revascularization procedures using indocyanine green angiography.
AB  - The aim of the present study is to assess the effects of unilateral
      revascularization on the contralateral foot circulation using indocyanine green
      (ICG). From January 2016 to April 2016, a total of twenty-one patients were
      included in this study. The patients underwent elective unilateral
      revascularization at our institution and we evaluated the feet circulation by
      indocyanine green angiography (ICGA) tests preoperatively and postoperatively.
      The ICGA parameters included the magnitude of intensity from the onset of ICG to
      the maximum intensity (Imax), the time from the onset of ICG to the maximum
      intensity (Tmax), and the time required to reach the half maximum intensity from
      the onset of ICG (T1/2). There were significant differences in the treated limb
      Tmax (P = 0.016) and T1/2 (P = 0.013) values and in the contralateral limb Tmax
      (P = 0.013), and T1/2 (P < 0.001) values on the perioperative ICGA tests. These
      results reflect the increase in skin perfusion in the treated limb and the
      decrease in skin perfusion in the contralateral limb. Unilateral
      revascularization decreases contralateral foot circulation. The preoperative
      contralateral lesion should be evaluated when revascularization is performed.

PMID- 29170486
TI  - Effects of lipid emulsion particle size on satiety and energy intake: a
      randomised cross-over trial.
AB  - BACKGROUND/OBJECTIVES: Emulsified lipids, with central lipid core surrounded by
      polar lipid 'protective coat', have been proposed to stimulate the ileal brake,
      alter appetite, food intake and aid weight control. In addition to lipid
      composition, emulsion particle size may contribute to efficacy with small
      droplets providing a larger surface area for gastrointestinal (GI) lipase action
      and larger droplets prolonging and delaying digestion in the GI tract. Tube
      feeding studies delivering emulsions directly into the small intestine show clear
      effects of smaller particle size on appetite and food intake, but evidence from
      oral feeding studies is sparse. The objective of this study was to determine the
      effects of lipid emulsion particle size on appetite response and food intake.
      SUBJECTS/METHODS: In a three-arm randomised cross-over, high-phospholipid (PL)
      dairy lipid emulsions or matched control were consumed at breakfast within a
      yoghurt smoothie: (i) large-particle size emulsion, LPE (diameter 0.759 um, 10 g
      lipid emulsion, 190 g yoghurt), (ii) small-particle size emulsion, SPE (diameter
      0.290 um, 10 g lipid emulsion, 190 g yoghurt), (iii) control non-emulsion, NE (10
      g non-emulsion lipid, 190 g yoghurt). Twenty male participants completed the
      study, where postprandial appetite response was rated using visual analogue
      scales (VAS) and ad libitum energy intake at a lunch meal measured 3 h later.
      RESULTS: There was a trend for LPE to suppress hunger (P = 0.08) and enhance
      fullness (P = 0.24) relative to both SPE and NE but not statistically
      significant, and no significant effect of either emulsion on food intake at the
      lunch meal (P > 0.05). CONCLUSIONS: Altering particle size of a high-PL emulsion
      did not enhance satiety or alter eating behaviour in a group of lean men.

PMID- 29170485
TI  - Aberrant perfusion and its connectivity within default mode network of first
      episode drug-naive schizophrenia patients and their unaffected first-degree
      relatives.
AB  - Neural substrates behind schizophrenia (SZ) and its heritability mediated by
      brain function are largely unknown. Cerebral blood flow (CBF), as a biomarker of
      activation in the brain, reflects the neuronal metabolism, and is promisingly
      used to detect cerebral alteration thereby shedding light on the features of
      individuals at high genetic risk. We performed a cross-sectional functional
      magnetic resonance imaging (MRI) study enrolling 45 first-episode drug-naive
      patients with SZ, 32 unaffected first-degree relatives of these patients, and 51
      healthy controls (HCs). We examined CBF, CBF connectivity, and CBF topological
      properties. SZ patients showed increased CBF in the left medial superior frontal
      gyrus and right precuneus compared with HCs, and decreased CBF in the left middle
      temporal gyrus compared with their relatives. Furthermore, unaffected relatives
      revealed higher level of CBF pronounced in regions within default mode network
      (DMN). Both SZ patients and their relatives exhibited dysconnectivity patterns.
      Notably, as for the network properties, unaffected relatives were with an
      intermediate level between SZ patients and HCs in the local efficiency and global
      efficiency. Our findings demonstrate the aberrant CBF of areas within DMN and the
      CBF connectivity pattern might be a familial feature in the brain of first
      episode SZ patients and their relatives.

PMID- 29170487
TI  - Lysine Possesses the Optimal Chain Length for Histone Lysine Methyltransferase
      Catalysis.
AB  - Histone lysine methyltransferases (KMTs) represent an important class of
      epigenetic enzymes that play essential roles in regulation of gene expression in
      humans. Members of the KMT family catalyze the transfer of the methyl group from
      S-adenosylmethionine (SAM) to lysine residues in histone tails and core histones.
      Here we report combined MALDI-TOF MS experiments, NMR analyses and quantum
      mechanical/molecular dynamics studies on human KMT-catalyzed methylation of the
      most related shorter and longer lysine analogues, namely ornithine and
      homolysine, in model histone peptides. Our experimental work demonstrates that
      while lysine is an excellent natural substrate for KMTs, ornithine and homolysine
      are not. This study reveals that ornithine does not undergo KMT-catalyzed
      methylation reactions, whereas homolysine can be methylated by representative
      examples of human KMTs. The results demonstrate that the specificity of KMTs is
      highly sensitive to the side chain length of the residue to be methylated. The
      origin for the degree of the observed activities of KMTs on ornithine and
      homolysine is discussed.

PMID- 29170488
TI  - Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs.
AB  - MicroRNAs regulate the expression of many proteins and require specific
      maturation steps. Primary microRNA transcripts (pri-miRs) are cleaved by
      Microprocessor, a complex containing the RNase Drosha and its partner protein,
      DGCR8. Although DGCR8 is known to bind heme, the molecular role of heme in pri
      miR processing is unknown. Here we show that heme is critical for Microprocessor
      to process pri-miRs with high fidelity. Furthermore, the degree of inherent heme
      dependence varies for different pri-miRs. Heme-dependent pri-miRs fail to
      properly recruit Drosha, but heme-bound DGCR8 can correct erroneous binding
      events. Rather than changing the oligomerization state, heme induces a
      conformational change in DGCR8. Finally, we demonstrate that heme activates DGCR8
      to recognize pri-miRs by specifically binding the terminal loop near the 3'
      single-stranded segment.

PMID- 29170490
TI  - The steady enhancement of the Australian Summer Monsoon in the last 200 years.
AB  - A new bicentennial series of the Australian monsoon strength based on historical
      wind observations has allowed for the assessment of the variability of this
      system since the early 19th century. Our series covers a period in which the
      scarcity of meteorological observations in the area had precluded the evaluation
      of long-term climatic trends. Results indicate that the increase in precipitation
      over Northern Australia reported for the last 60 years is just a manifestation of
      a much longer lasting trend related to the strengthening of the Australian
      monsoon that has been occurring since at least 1816.

PMID- 29170489
TI  - Prokaryotic soluble expression and purification of bioactive human fibroblast
      growth factor 21 using maltose-binding protein.
AB  - Human fibroblast growth factor 21 (hFGF21) has been characterized as an important
      regulator of glucose and lipid metabolism homeostasis. Here, to produce hFGF21
      efficiently in Escherichia coli, the expression and solubility of hFGF21 were
      tested and optimised by fusing the protein with one of eight tags: hexahistidine
      (His6), thioredoxin (Trx), small ubiquitin-related modifier (Sumo), glutathione S
      transferase (GST), maltose-binding protein (MBP), N-utilisation substance protein
      A (NusA), human protein disulphide isomerase (PDI), and the b'a' domain of PDI
      (PDIb'a'). Each tag increased solubility of the protein when the expression
      temperature was 18 degrees C. Unlike many other tags that were tested, MBP
      significantly enhanced the solubility of the protein also in the culture
      condition at 37 degrees C. Thus, the MBP-hFGF21 construct was further pursued for
      optimisation of affinity chromatography purification. After tag removal, 8.1 mg
      of pure hFGF21 was obtained as a final product from 500 mL of starting culture.
      The protein was then characterised by mass spectroscopy and an in vitro
      functional assay using NIH-3T3 cells transfected with a beta-klotho reporter
      gene. These characteristics are similar to those of commercial hFGF21. Thus, the
      MBP tag is useful for efficient prokaryotic production and purification of
      bioactive hFGF21.

PMID- 29170491
TI  - Crystallite size-dependent metastable phase formation of TiAlN coatings.
AB  - It is well known that surface energy differences thermodynamically stabilize
      nanocrystalline gamma-Al2O3 over alpha-Al2O3. Here, through correlative ab initio
      calculations and advanced material characterization at the nanometer scale, we
      demonstrate that the metastable phase formation of nanocrystalline TiAlN, an
      industrial benchmark coating material, is crystallite size-dependent. By relating
      calculated surface and volume energy contributions to the total energy, we
      predict the chemical composition-dependent phase boundary between the two
      metastable solid solution phases of cubic and wurzite Ti1-xAlxN. This phase
      boundary is characterized by the critical crystallite size d critical .
      Crystallite size-dependent phase stability predictions are in very good agreement
      with experimental phase formation data where x was varied by utilizing
      combinatorial vapor phase condensation. The wide range of critical Al
      solubilities for metastable cubic Ti1-xAlxN from x max = 0.4 to 0.9 reported in
      literature and the sobering disagreement thereof with DFT predictions can at
      least in part be rationalized based on the here identified crystallite size
      dependent metastable phase formation. Furthermore, it is evident that predictions
      of critical Al solubilities in metastable cubic TiAlN are flawed, if the
      previously overlooked surface energy contribution to the total energy is not
      considered.

PMID- 29170492
TI  - Prediction of plasma efavirenz concentrations among HIV-positive patients taking
      efavirenz-containing combination antiretroviral therapy.
AB  - We investigated the predictors of plasma mid-dose concentrations (C12) of
      efavirenz by enrolling 456 HIV-positive patients who had received 2 nucleos(t)ide
      reverse-transcriptase inhibitors plus efavirenz (600 mg daily) for 2 weeks or
      longer and had their CYP2B6 516G>T polymorphism and efavirenz C12 determined. The
      median efavirenz C12 was 2.41 mg/L (IQR, 1.93-3.14). In analysis of covariance
      models, patients with CYP2B6 516GT and TT genotypes compared to those with GG
      genotype had higher efavirenz C12 (for GT genotype, an increase by 0.976 mg/L
      [95%CI, 0.765-1.188], and TT genotype, 4.871 mg/L [95%CI, 4.126-5.616]), while
      per 10-kg increment in weight decreased C12 by 0.199 mg/L (95%CI, 0.111-0.287).
      Models incorporating CYP2B6 516G>T polymorphism and weight had moderate
      predictive values in predicting efavirenz C12 >= 2 mg/L (ROC area under curve =
      0.706 [95%CI, 0.656-0.756]). In the absence of CYP2B6 516G>T polymorphism, weight
      <=58 kg provided better predictabilities for efavirenz C12 >= 2 mg/L
      (probability, 77.1% [95%CI, 69.0-83.5%] for weight = 50 kg and 70.6% [95%CI, 64.1
      76.4%] for weight = 58 kg).

PMID- 29170493
TI  - The molecular basis of phosphite and hypophosphite recognition by ABC
      transporters.
AB  - Inorganic phosphate is the major bioavailable form of the essential nutrient
      phosphorus. However, the concentration of phosphate in most natural habitats is
      low enough to limit microbial growth. Under phosphate-depleted conditions some
      bacteria utilise phosphite and hypophosphite as alternative sources of
      phosphorus, but the molecular basis of reduced phosphorus acquisition from the
      environment is not fully understood. Here, we present crystal structures and
      ligand binding affinities of periplasmic binding proteins from bacterial
      phosphite and hypophosphite ATP-binding cassette transporters. We reveal that
      phosphite and hypophosphite specificity results from a combination of steric
      selection and the presence of a P-H...pi interaction between the ligand and a
      conserved aromatic residue in the ligand-binding pocket. The characterisation of
      high affinity and specific transporters has implications for the marine
      phosphorus redox cycle, and might aid the use of phosphite as an alternative
      phosphorus source in biotechnological, industrial and agricultural applications.

PMID- 29170494
TI  - Phosphate-Solubilizing Bacteria Nullify the Antagonistic Effect of Soil
      Calcification on Bioavailability of Phosphorus in Alkaline Soils.
AB  - Phosphate-solubilizing bacteria (PSB) reduce the negative effects of soil
      calcification on soil phosphorus (P) nutrition. In this incubation study, we
      explored the ability of PSB (control and inoculated) to release P from different
      P sources [single super phosphate (SSP), rock phosphate (RP), poultry manure (PM)
      and farm yard manure (FYM)] with various soil lime contents (4.78, 10, 15 and
      20%) in alkaline soil. PSB inoculation progressively enriched Olsen extractable P
      from all sources compared to the control over the course of 56 days; however,
      this increase was greater from organic sources (PM and FYM) than from mineral P
      sources (SSP and RP). Lime addition to the soil decreased bioavailable P, but
      this effect was largely neutralized by PSB inoculation. PSB were the most viable
      in soil inoculated with PSB and amended with organic sources, while lime addition
      decreased PSB survival. Our findings imply that PSB inoculation can counteract
      the antagonistic effect of soil calcification on bioavailable P when it is
      applied using both mineral and organic sources, although organic sources support
      this process more efficiently than do mineral P sources. Therefore, PSB
      inoculation combined with organic manure application is one of the best options
      for improving soil P nutrition.

PMID- 29170495
TI  - First-trimester vaginal microbiome diversity: A potential indicator of preterm
      delivery risk.
AB  - Preterm birth is a leading cause of global neonate mortality. Hospitalization
      costs associated with preterm deliveries present a huge economic burden. Existing
      physical/biochemical markers for predicting preterm birth risk are mostly suited
      for application at mid/late pregnancy stages, thereby leaving very short time
      (between diagnosis and delivery) for adopting appropriate intervention
      strategies. Recent studies indicating correlations between pre/full-term delivery
      and the composition of vaginal microbiota in pregnant women have opened new
      diagnostic possibilities. In this study, we performed a thorough meta-analysis of
      vaginal microbiome datasets to evaluate the utility of popular diversity and
      inequality measures for predicting, at an early stage, the risk of preterm
      delivery. Results indicate significant differences (in diversity measures)
      between 'first-trimester' vaginal microbiomes obtained from women with term and
      preterm outcomes, indicating the potential diagnostic utility of these measures.
      In this context, we introduce a novel diversity metric that has significantly
      better diagnostic ability as compared to established diversity measures. The
      metric enables 'early' and highly accurate prediction of preterm delivery
      outcomes, and can potentially be deployed in clinical settings for preterm birth
      risk-assessment. Our findings have potentially far reaching implications in the
      fight against neonatal deaths due to preterm birth.

PMID- 29170496
TI  - Genome-wide analysis of circular RNAs in prenatal and postnatal pituitary glands
      of sheep.
AB  - Circular RNAs (circRNAs) are a class of animal non-coding RNAs and play an impor
      tant role in animal growth and development. However, the expression and function
      of circRNAs in the pituitary gland of sheep are unclear. Transcriptome profiling
      of circRNAs in the pituitary gland of sheep may enable us to understand their
      biological functions. In the present study, we identified 10,226 circRNAs from
      RNA-seq data in the pituitary gland of prenatal and postnatal sheep. Reverse
      transcription PCR and DNA sequencing analysis confirmed the presence of several
      circRNAs. Real-time RT-PCR analysis showed that sheep circRNAs are resistant to
      RNase R digestion and are expressed in prenatal and postnatal pituitary glands.
      GO and KEGG enrichment analysis showed that host genes of differentially
      expressed circRNAs are involved in the regulation of hormone secretion as well as
      in several pathways related to these processes. We determined that numerous
      circRNAs interact with pituitary-specific miRNAs that are involved in the
      biologic functions of the pituitary gland. Moreover, several circRNAs contain at
      least one IRES element and open reading frame, indicating their potential to
      encode proteins. Our study provides comprehensive expression profiles of circRNAs
      in the pituitary gland, thereby offering a valuable resource for circRNA biology
      in sheep.

PMID- 29170497
TI  - Divergent synthesis of N-heterocycles via controllable cyclization of azido
      diynes catalyzed by copper and gold.
AB  - Gold-catalyzed intermolecular alkyne oxidation by an N-O bond oxidant has proven
      to be a powerful method in organic synthesis during the past decade, because this
      approach would enable readily available alkynes as precursors in generating alpha
      oxo gold carbenes. Among those, gold-catalyzed oxidative cyclization of dialkynes
      has received particular attention as this chemistry offers great potential to
      build structurally complex cyclic molecules. However, these alkyne oxidations
      have been mostly limited to noble metal catalysts, and, to our knowledge, non
      noble metal-catalyzed reactions such as diyne oxidations have not been reported.
      Herein, we disclose a copper-catalyzed oxidative diyne cyclization, allowing the
      facile synthesis of a wide range of valuable pyrrolo[3,4-c]quinolin-1-ones.
      Interestingly, by employing the same starting materials, the gold-catalyzed
      cascade cyclization leads to the divergent formation of synthetically useful
      pyrrolo[2,3-b]indoles. Furthermore, the proposed mechanistic rationale for these
      cascade reactions is strongly supported by both control experiments and
      theoretical calculations.

PMID- 29170498
TI  - A structurally distinct TGF-beta mimic from an intestinal helminth parasite
      potently induces regulatory T cells.
AB  - Helminth parasites defy immune exclusion through sophisticated evasion
      mechanisms, including activation of host immunosuppressive regulatory T (Treg)
      cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg
      population by secreting products that activate TGF-beta signalling, but the
      identity of the active molecule is unknown. Here we identify an H. polygyrus TGF
      beta mimic (Hp-TGM) that replicates the biological and functional properties of
      TGF-beta, including binding to mammalian TGF-beta receptors and inducing mouse
      and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-beta or
      other members of the TGF-beta family, but is a member of the complement control
      protein superfamily. Thus, our data indicate that through convergent evolution,
      the parasite has acquired a protein with cytokine-like function that is able to
      exploit an endogenous pathway of immunoregulation in the host.

PMID- 29170500
TI  - White matter disease: Targeted aspartoacylase gene therapy reverts Canavan
      disease.

PMID- 29170499
TI  - DNA double-strand break repair pathway regulates PD-L1 expression in cancer
      cells.
AB  - Accumulating evidence suggests that exogenous cellular stress induces PD-L1
      upregulation in cancer. A DNA double-strand break (DSB) is the most critical type
      of genotoxic stress, but the involvement of DSB repair in PD-L1 expression has
      not been investigated. Here we show that PD-L1 expression in cancer cells is
      upregulated in response to DSBs. This upregulation requires ATM/ATR/Chk1 kinases.
      Using an siRNA library targeting DSB repair genes, we discover that BRCA2
      depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or PARP
      inhibition. In addition, we show that Ku70/80 depletion substantially enhances PD
      L1 upregulation after X-rays. The upregulation by Ku80 depletion requires Chk1
      activation following DNA end-resection by Exonuclease 1. DSBs activate STAT1 and
      STAT3 signalling, and IRF1 is required for DSB-dependent PD-L1 upregulation.
      Thus, our findings reveal the involvement of DSB repair in PD-L1 expression and
      provide mechanistic insight into how PD-L1 expression is regulated after DSBs.

PMID- 29170502
TI  - Multiple sclerosis: 10-year study shines a light on grey matter atrophy in MS.

PMID- 29170503
TI  - Mutational and putative neoantigen load predict clinical benefit of adoptive T
      cell therapy in melanoma.
AB  - Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has
      yielded remarkable response rates and many durable responses in clinical trials
      in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we
      searched for predictive biomarkers to ACT in melanoma. Whole exome- and
      transcriptome sequencing and neoantigen prediction were applied to pre-treatment
      samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage
      IV melanoma. All patients had previously progressed on other immunotherapies. We
      report that clinical benefit is associated with significantly higher predicted
      neoantigen load. High mutation and predicted neoantigen load are significantly
      associated with improved progression-free and overall survival. Further, clinical
      benefit is associated with the expression of immune activation signatures
      including a high MHC-I antigen processing and presentation score. These results
      improve our understanding of mechanisms behind clinical benefit of ACT in
      melanoma.

PMID- 29170504
TI  - Characterization of large and small-plaque variants in the Zika virus clinical
      isolate ZIKV/Hu/S36/Chiba/2016.
AB  - An Asian/American lineage Zika virus (ZIKV) strain ZIKV/Hu/S36/Chiba/2016 formed
      2 types in plaque size, large and small. Genomic analysis of the plaque-forming
      clones obtained from the isolate indicated that the clones forming small plaques
      commonly had an adenine nucleotide at position 796 (230Gln in the amino acid
      sequence), while clones forming large plaques had a guanine nucleotide (230Arg)
      at the same position, suggesting that this position was associated with the
      difference in plaque size. Growth kinetics of a large-plaque clone was faster
      than that of a small-plaque clone in Vero cells. Recombinant ZIKV G796A/rZIKV
      MR766, which carries a missense G796A mutation, was produced using an infectious
      molecular clone of the ZIKV MR766 strain rZIKV-MR766/pMW119-CMVP. The plaque size
      of the G796A mutant was significantly smaller than that of the parental strain.
      The G796A mutation clearly reduced the growth rate of the parental virus in Vero
      cells. Furthermore, the G796A mutation also decreased the virulence of the MR766
      strain in IFNAR1 knockout mice. These results indicate that the amino acid
      variation at position 230 in the viral polyprotein, which is located in the M
      protein sequence, is a molecular determinant for plaque morphology, growth
      property, and virulence in mice of ZIKV.

PMID- 29170505
TI  - Ilizarov external fixation versus plate internal fixation in the treatment of end
      stage ankle arthritis: decision analysis of clinical parameters.
AB  - The purpose of this study was to evaluate the effect of Ilizarov external
      fixation (IEF) and plate internal fixation (PIF) in the treatment of end-stage
      ankle arthritis on pain relieving and function improvement. The study cohort
      consisted of 59 patients with end-stage ankle arthritis underwent ankle
      arthrodesis with IEF or PIF between June 2011 and June 2015. Standard radiographs
      and computed tomography (CT) scans were obtained before surgery and during the
      follow-up. Functional assessments were performed using Foot and Ankle pain score
      of American Orthopedics Foot and Ankle Society (AOFAS) and Visual Analogue Scale
      (VAS). The average AOFAS scores in both IEF group and PIF groups increased
      significantly after operation, from 45.5 +/- 6.3 to 84.8 +/- 4.9 and from 45.9 +/
      6.6 to 86.6 +/- 5.4, respectively. The average VAS scores in both groups
      decreased significantly after operation, from 8.4 +/- 1.9 to 2.5 +/- 0.6 and from
      8.2 +/- 1.5 to 2.3 +/- 0.7, respectively. Nevertheless, there was no significant
      difference for preoperative or postoperative AOFAS and VAS scores between the two
      groups. The IEF would result in comparable postoperative functional recovery and
      pain relieving to PIF and may be an effective substitute to PIF in the treatment
      of end-stage ankle arthritis.

PMID- 29170501
TI  - Idiopathic REM sleep behaviour disorder and neurodegeneration - an update.
AB  - So-called idiopathic rapid eye movement (REM) sleep behaviour disorder (RBD),
      formerly seen as a rare parasomnia, is now recognized as the prodromal stage of
      an alpha-synucleinopathy. Given the very high risk that patients with idiopathic
      RBD have of developing alpha-synucleinopathies, such as Parkinson disease (PD),
      PD dementia, dementia with Lewy bodies or multiple system atrophy, and the
      outstandingly high specificity and very long interval between the onset of
      idiopathic RBD and the clinical manifestations of alpha-synucleinopathies, the
      prodromal phase of this disorder represents a unique opportunity for potentially
      disease-modifying intervention. This Review provides an update on classic and
      novel biomarkers of alpha-synuclein-related neurodegeneration in patients with
      idiopathic RBD, focusing on advances in imaging and neurophysiological,
      cognitive, autonomic, tissue-specific and other biomarkers. We discuss the
      strengths, potential weaknesses and suitability of these biomarkers for
      identifying RBD and neurodegeneration, with an emphasis on predicting progression
      to overt alpha-synucleinopathy. The role of video polysomnography in providing
      quantifiable and potentially treatment-responsive biomarkers of neurodegeneration
      is highlighted. In light of all these advances, and the now understood role of
      idiopathic RBD as an early manifestation of alpha-synuclein disease, we call for
      idiopathic RBD to be reconceptualized as isolated RBD.

PMID- 29170506
TI  - Daily Time-Use Patterns and Obesity and Mental Health among Primary School
      Students in Shanghai: A Population-Based Cross-Sectional Study.
AB  - Physical activity, screen viewing, sleep, and homework among children have been
      independently linked to health outcomes. However, few studies have assessed the
      independent associations between time spent in daily activities and children's
      physical and mental health. This study describes time spent in four activities
      among primary school students in Shanghai, and examines the relationship between
      daily time-use patterns and obesity and mental health. The representative sample
      consists of 17,318 children aged 6-11 years in Shanghai. Time spent in moderate
      to vigorous physical activities (MVPA), screen viewing, sleep, and homework was
      measured by validated questionnaires. Logistic regressions were performed. We
      also fitted generalized additive models (GAM) and performed two-objective
      optimization to minimize the probability of poor mental health and obesity. In
      2014, 33.7% of children spent ?1 hour/day on MVPA, 15.6% spent >= 2 hours/day on
      screen viewing, 12.4% spent ? 9 hours/day on sleep, and 27.2% spent >= 2
      hours/day on homework. The optimization results suggest that considering the 24
      hour time limit, children face trade-offs when allocating time. A priority should
      be given to the duration of sleep and MVPA. Screen exposure should be minimized
      to save more time for sleep and other beneficial activities.

PMID- 29170507
TI  - Increased core body temperature in astronauts during long-duration space
      missions.
AB  - Humans' core body temperature (CBT) is strictly controlled within a narrow range.
      Various studies dealt with the impact of physical activity, clothing, and
      environmental factors on CBT regulation under terrestrial conditions. However,
      the effects of weightlessness on human thermoregulation are not well understood.
      Specifically, studies, investigating the effects of long-duration spaceflight on
      CBT at rest and during exercise are clearly lacking. We here show that during
      exercise CBT rises higher and faster in space than on Earth. Moreover, we
      observed for the first time a sustained increased astronauts' CBT also under
      resting conditions. This increase of about 1  degrees C developed gradually over
      2.5 months and was associated with augmented concentrations of interleukin-1
      receptor antagonist, a key anti-inflammatory protein. Since even minor increases
      in CBT can impair physical and cognitive performance, both findings have a
      considerable impact on astronauts' health and well-being during future long-term
      spaceflights. Moreover, our findings also pinpoint crucial physiological
      challenges for spacefaring civilizations, and raise questions about the
      assumption of a thermoregulatory set point in humans, and our evolutionary
      ability to adapt to climate changes on Earth.

PMID- 29170508
TI  - Differential distribution of Y-chromosome haplotypes in Swiss and Southern
      European goat breeds.
AB  - The analysis of Y-chromosome variation has provided valuable clues about the
      paternal history of domestic animal populations. The main goal of the current
      work was to characterize Y-chromosome diversity in 31 goat populations from
      Central Eastern (Switzerland and Romania) and Southern Europe (Spain and Italy)
      as well as in reference populations from Africa and the Near East. Towards this
      end, we have genotyped seven single nucleotide polymorphisms (SNPs), mapping to
      the SRY, ZFY, AMELY and DDX3Y Y-linked loci, in 275 bucks from 31 populations. We
      have observed a low level of variability in the goat Y-chromosome, with just five
      haplotypes segregating in the whole set of populations. We have also found that
      Swiss bucks carry exclusively Y1 haplotypes (Y1A: 24%, Y1B1: 15%, Y1B2: 43% and
      Y1C: 18%), while in Italian and Spanish bucks Y2A is the most abundant haplotype
      (77%). Interestingly, in Carpathian goats from Romania the Y2A haplotype is also
      frequent (42%). The high Y-chromosome differentiation between Swiss and
      Italian/Spanish breeds might be due to the post-domestication spread of two
      different Near Eastern genetic stocks through the Danubian and Mediterranean
      corridors. Historical gene flow between Southern European and Northern African
      goats might have also contributed to generate such pattern of genetic
      differentiation.

PMID- 29170509
TI  - Measuring tissue displacement of the anterior vaginal wall using the novel
      aspiration technique in vivo.
AB  - Little is known about the mechanical properties of pelvic floor structures and
      their role in the course and treatment of pelvic organ prolapse (POP). We
      hypothesize that in vivo mechanical properties of the vaginal wall are related to
      the appearance of POP and pre-and post-operative states. We used a suction device
      for intravaginal application, the aspiration device, to evaluate two in vivo
      mechanical parameters of the anterior vaginal wall, the load dependent tissue
      displacement and the initial displacement, by image analysis in pre- and post
      menopausal women with (POP) and without (control) cystocele (POP: pre-menopausal:
      N = 6, post-menopausal: N = 19, control: pre-menopausal: N = 17, post-menopausal:
      N = 6). Mechanical parameters in women with and without cystocele and pre- and
      post-operative parameters were compared. Statistically significant differences
      were observed between the two mechanical parameters in pre- and post-operative
      states (P = 0.04, P = 0.03), but not between the parameters for women with and
      without cystocele (P = 0.92, P = 0.75). The mechanical behavior of pelvic floor
      structures is influenced by factors such as POP, age or estrogenization that are
      apparent at different length scales, which cannot be separated by the aspiration
      based biomechanical measurements. When comparing pre- and post-operative states
      of the same patient, a firmer tissue response was observed after intervention.

PMID- 29170510
TI  - Whole blood stabilization for the microfluidic isolation and molecular
      characterization of circulating tumor cells.
AB  - Precise rare-cell technologies require the blood to be processed immediately or
      be stabilized with fixatives. Such restrictions limit the translation of
      circulating tumor cell (CTC)-based liquid biopsy assays that provide accurate
      molecular data in guiding clinical decisions. Here we describe a method to
      preserve whole blood in its minimally altered state by combining hypothermic
      preservation with targeted strategies that counter cooling-induced platelet
      activation. Using this method, whole blood preserved for up to 72 h can be
      readily processed for microfluidic sorting without compromising CTC yield and
      viability. The tumor cells retain high-quality intact RNA suitable for single
      cell RT-qPCR as well as RNA-Seq, enabling the reliable detection of cancer
      specific transcripts including the androgen-receptor splice variant 7 in a cohort
      of prostate cancer patients with an overall concordance of 92% between fresh and
      preserved blood. This work will serve as a springboard for the dissemination of
      diverse blood-based diagnostics.

PMID- 29170511
TI  - T cell-targeting nanoparticles focus delivery of immunotherapy to improve
      antitumor immunity.
AB  - Targeted delivery of compounds to particular cell subsets can enhance therapeutic
      index by concentrating their action on the cells of interest. Because attempts to
      target tumors directly have yielded limited benefit, we instead target endogenous
      immune cell subsets in the circulation that can migrate actively into tumors. We
      describe antibody-targeted nanoparticles that bind to CD8+ T cells in the blood,
      lymphoid tissues, and tumors of mice. PD-1+ T cells are successfully targeted in
      the circulation and tumor. The delivery of an inhibitor of TGFbeta signaling to
      PD-1-expressing cells extends the survival of tumor-bearing mice, whereas free
      drugs have no effect at such doses. This modular platform also enables PD-1
      targeted delivery of a TLR7/8 agonist to the tumor microenvironment, increasing
      the proportion of tumor-infiltrating CD8+ T cells and sensitizing tumors to
      subsequent anti-PD-1. Targeted delivery of immunotherapy to defined subsets of
      endogenous leukocytes may be superior to administration of free drugs.

PMID- 29170513
TI  - Publisher Correction: Greenhouse and field evaluation of isoxaflutole for weed
      control in maize in China.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29170512
TI  - Generation of interspecies limited chimeric nephrons using a conditional nephron
      progenitor cell replacement system.
AB  - Animal fetuses and embryos may have applications in the generation of human
      organs. Progenitor cells may be an appropriate cell source for regenerative
      organs because of their safety and availability. However, regenerative organs
      derived from exogenous lineage progenitors in developing animal fetuses have not
      yet been obtained. Here, we established a combination system through which donor
      cells could be precisely injected into the nephrogenic zone and native nephron
      progenitor cells (NPCs) could be eliminated in a time- and tissue-specific
      manner. We successfully achieved removal of Six2+ NPCs within the nephrogenic
      niche and complete replacement of transplanted NPCs with donor cells. These NPCs
      developed into mature glomeruli and renal tubules, and blood flow was observed
      following transplantation in vivo. Furthermore, this artificial nephron could be
      obtained using NPCs from different species. Thus, this technique enables in vivo
      differentiation from progenitor cells into nephrons, providing insights into
      nephrogenesis and organ regeneration.

PMID- 29170514
TI  - Synthesis of uniform single layer WS2 for tunable photoluminescence.
AB  - Two-dimensional transition metal dichalcogenides (2D TMDs) have gained great
      interest due to their unique tunable bandgap as a function of the number of
      layers. Especially, single-layer tungsten disulfides (WS2) is a direct band gap
      semiconductor with a gap of 2.1 eV featuring strong photoluminescence and large
      exciton binding energy. Although synthesis of MoS2 and their layer dependent
      properties have been studied rigorously, little attention has been paid to the
      formation of single-layer WS2 and its layer dependent properties. Here we report
      the scalable synthesis of uniform single-layer WS2 film by a two-step chemical
      vapor deposition (CVD) method followed by a laser thinning process. The PL
      intensity increases six-fold, while the PL peak shifts from 1.92 eV to 1.97 eV
      during the laser thinning from few-layers to single-layer. We find from the
      analysis of exciton complexes that both a neutral exciton and a trion increases
      with decreasing WS2 film thickness; however, the neutral exciton is predominant
      in single-layer WS2. The binding energies of trion and biexciton for single-layer
      WS2 are experimentally characterized at 35 meV and 60 meV, respectively. The
      tunable optical properties by precise control of WS2 layers could empower a great
      deal of flexibility in designing atomically thin optoelectronic devices.

PMID- 29170515
TI  - Prognostic Value of Long Non-Coding RNA HULC and MALAT1 Following the Curative
      Resection of Hepatocellular Carcinoma.
AB  - Long non-coding RNAs (lncRNAs) were shown to be the crucial regulators of the
      many diseases. In this study, the expressions of lncRNAs were investigated in
      resected 158 hepatocellular carcinomas (HCCs) to evaluate the effects of their
      expression levels on prognosis. The expression levels of HULC and MALAT1 were
      shown to be significantly higher in the normal background tissue of HCC than
      those in the normal liver tissue of metastatic liver tumor without hepatitis
      (HULC: fold change 14.9, P = 1.7e-06; MALAT1: fold change 17.5, P = 1.2e-06. The
      formation of capsule was shown to be correlated with the increased expression of
      HULC (P = 0.041), while the size of HCC under 2 cm was correlated with a decrease
      in MALAT1 expression (P = 0.019). The levels of serum alpha-fetoprotein above 20
      ng/mL indicated a decreased expression of both HULC and MALAT1 (HULC: P = 0.017;
      MALAT1: P = 0.0036). The increase in the expression levels of MALAT1 in HCC
      tissues was significantly correlated with better overall survival (HULC: P =
      0.099, MALAT1: P = 0.028). Thus, the expression of these lncRNAs in HCC
      potentially correlates with the HCC malignancy and they represent potential
      prognostic biomarkers of the resected HCC.

PMID- 29170516
TI  - Metabolic Differences in Glutamine Utilization Lead to Metabolic Vulnerabilities
      in Prostate Cancer.
AB  - The new oncologic paradigm of precision medicine is focused on identifying
      metabolic, proteomic, transcriptomic and genomic variabilities in tumors that can
      be exploited to tailor treatments and improve patient outcomes. Metabolic changes
      are a hallmark of cancer, and inhibition of metabolic pathways is now a major
      strategy in medicinal chemistry for targeting cancers. However, non-invasive
      biomarkers to categorize metabolic subtypes are in short supply. The purpose of
      this study was to characterize the intracellular and extracellular metabolic
      profiles of four prostate cancer cell lines with varying degrees of
      aggressiveness. We observed metabolic differences between the aggressive prostate
      cancer cell line PC3 and the even more aggressive, metastatic subline PC3M
      assessed by hyperpolarized in vivo pyruvate studies, nuclear magnetic resonance
      spectroscopy, and carbon-13 feeding studies. On further examination of the
      differences between these two cell lines, we found increased glutamine
      utilization in the metastatic PC3M subline that led directly to sensitivity to
      glutaminase inhibitor CB-839. Our study supports the theory that metastatic
      progression increases glutamine utilization and the inhibition of glutaminolysis
      could have clinical implications.

PMID- 29170517
TI  - Direct evidence of multichannel-improved charge-carrier mechanism for enhanced
      photocatalytic H2 evolution.
AB  - In the field of photocatalysis, the high-charge recombination rate has been the
      big challenge to photocatalytic conversion efficiency. Here we demonstrate the
      direct evidence of multichannel-improved charge-carrier mechanism to facilitate
      electron-hole transfer for raising photocatalytic H2 evolution activity. Scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and UV-Vis diffuse
      reflectance spectroscopy (DRS), were used to characterize the as-fabricated
      samples. The result shows that the present design of Au/Pt nanoparticles (NPs)
      decorated one-dimensional Z-scheme TiO2/WO3 heterostructure composite nanofibers
      have been fabricated, which even exhibited excellent light absorption in the
      visible region and greatly enhanced photocatalytic activities on H2 generation
      comparing with pure TiO2, TiO2/WO3 and Pt/WO3/TiO2 nanofibers. This
      greatpromotion is mainly on account of the photosynthetic heterojunction system,
      which include the surface plasmon resonance (SPR) of Au nanoparticles, low
      overpotential of Pt nanoparticles, and more importantly, the one-dimensional
      multichannel-improved charge-carrier photosynthetic heterojunction system with Pt
      as an electron collector and WO3 as a hole collector. Transferring photoinduced
      electrons and holes at the same time, leading to effective charge separation was
      directly proved by ultraviolet photoelectron spectroscopy, electrochemical
      impedance spectroscopy, photocurrent analysis and incident photon-to-electron
      conversion spectrum.

PMID- 29170518
TI  - Second messenger analogues highlight unexpected substrate sensitivity of CD38:
      total synthesis of the hybrid "L-cyclic inosine 5'-diphosphate ribose".
AB  - The multifunctional, transmembrane glycoprotein human CD38 catalyses the
      synthesis of three key Ca2+-mobilising messengers, including cyclic adenosine 5'
      diphosphate ribose (cADPR), and CD38 knockout studies have revealed the relevance
      of the related signalling pathways to disease. To generate inhibitors of CD38 by
      total synthesis, analogues based on the cyclic inosine 5'-diphosphate ribose
      (cIDPR) template were synthesised. In the first example of a sugar hybrid cIDPR
      analogue, "L-cIDPR", the natural "northern" N1-linked D-ribose of cADPR was
      replaced by L-ribose. L-cIDPR is surprisingly still hydrolysed by CD38, whereas 8
      Br-L-cIDPR is not cleaved, even at high enzyme concentrations. Thus, the
      inhibitory activity of L-cIDPR analogues appears to depend upon substitution of
      the base at C-8; 8-Br-L-cIDPR and 8-NH2-L-cIDPR inhibit CD38-mediated cADPR
      hydrolysis (IC50 7 MUM and 21 uM respectively) with 8-Br-L-cIDPR over 20-fold
      more potent than 8-Br-cIDPR. In contrast, L-cIDPR displays a comparative 75-fold
      reduction in activity, but is only ca 2-fold less potent than cIDPR itself.
      Molecular modelling was used to explore the interaction of the CD38 catalytic
      residue Glu-226 with the "northern" ribose. We propose that Glu226 still acts as
      the catalytic residue even for an L-sugar substrate. 8-Br-L-cIDPR potentially
      binds non-productively in an upside-down fashion. Results highlight the key role
      of the "northern" ribose in the interaction of cADPR with CD38.

PMID- 29170519
TI  - Plasmonic enhanced low-threshold random lasing from dye-doped nematic liquid
      crystals with TiN nanoparticles in capillary tubes.
AB  - We report a plasmonic enhanced low-threshold random lasing from dye-doped nematic
      liquid crystals with titanium nitride (TiN) nanoparticles (NPDDNLC) in capillary
      tubes. The NPDDNLC sample yields a coherent random laser with about 0.3 nm in the
      full width at half maximum (FWHM). We find the laser threshold is decreased by
      introducing the TiN NPs into the dye-doped nematic liquid crystal sample. The
      laser threshold decreases with increasing the number density of TiN nanoparticles
      from 5.613 * 1010/ml to 5.314 * 1011/ml. We suggest that the low-threshold random
      laser is caused by the cooperative effect of the recurrent multiple scattering
      and field enhancement in the vicinity of TiN nanoparticles. The localized
      electric field near the TiN nanoparticles enhances the energy absorption of the
      dye and strengthens the fluorescence amplification. Moreover, we provide a new
      parameter (the relative efficiency of the stimulated radiation photons) to
      quantify the quality of the random laser, and we give expressions for the
      wavelength, mode, and whole emission spectrum. Finally, we find the emission
      spectrum depends strongly on the emission angle and we discuss the reasons. These
      findings provide a simple and efficient way for the realization of low-threshold
      random lasers with low cost.

PMID- 29170520
TI  - Integrated Proteomic and Metabolomic prediction of Term Preeclampsia.
AB  - Term preeclampsia (tPE), >=37 weeks, is the most common form of PE and the most
      difficult to predict. Little is known about its pathogenesis. This study aims to
      elucidate the pathogenesis and assess early prediction of tPE using serial
      integrated metabolomic and proteomic systems biology approaches. Serial first-
      (11-14 weeks) and third-trimester (30-34 weeks) serum samples were analyzed using
      targeted metabolomic (1H NMR and DI-LC-MS/MS) and proteomic (MALDI-TOF/TOF-MS)
      platforms. We analyzed 35 tPE cases and 63 controls. Serial first- (sphingomyelin
      C18:1 and urea) and third-trimester (hexose and citrate) metabolite screening
      predicted tPE with an area under the receiver operating characteristic curve
      (AUC) (95% CI) = 0.817 (0.732-0.902) and a sensitivity of 81.6% and specificity
      of 71.0%. Serial first [TATA box binding protein-associated factor (TBP)] and
      third-trimester [Testis-expressed sequence 15 protein (TEX15)] protein biomarkers
      highly accurately predicted tPE with an AUC (95% CI) of 0.987 (0.961-1.000),
      sensitivity 100% and specificity 98.4%. Integrated pathway over-representation
      analysis combining metabolomic and proteomic data revealed significant
      alterations in signal transduction, G protein coupled receptors, serotonin and
      glycosaminoglycan metabolisms among others. This is the first report of serial
      integrated and combined metabolomic and proteomic analysis of tPE. High
      predictive accuracy and potentially important pathogenic information were
      achieved.

PMID- 29170521
TI  - Age-dependent and regional heterogeneity in the long-chain base of A-series
      gangliosides observed in the rat brain using MALDI Imaging.
AB  - Alterations in the long chain base of the sphingosine moiety of gangliosides have
      been shown to play a role in neurodevelopment and neurodegeneration. Indeed, the
      accumulation of d20:1 sphingosine has been referred to as a metabolic marker of
      aging in the brain, however, this remains to be shown in simple gangliosides GM2
      and GM3. In this study, Matrix-assisted laser desorption/ionization Imaging Mass
      Spectrometry (MALDI IMS) was used to examine the neuroanatomical distribution of
      A-series gangliosides with either 18 or 20 carbon sphingosine chains (d18:1 or
      d20:1) in Fisher 344 rats across the lifespan. The ratio of d20:1/d18:1 species
      was determined across 11 regions of interest in the brain. Interestingly, a
      decrease in the d20:1/d18:1 ratio for GM2 and GM3 was observed during early
      development with the exception of the peri-ventricular corpus callosum, where an
      age-dependent increase was observed for ganglioside GM3. An age-dependent
      increase in d20:1 species was confirmed for complex gangliosides GM1 and GD1 with
      the most significant increase during early development and a high degree of
      anatomical heterogeneity during aging. The unique neuroanatomically-specific
      responses of d20:1 ganglioside abundance may lead to a better understanding of
      regional vulnerability to damage in the aging brain.

PMID- 29170522
TI  - Elevation in tropical sky islands as the common driver in structuring genes and
      communities of freshwater organisms.
AB  - Tropical mountains are usually characterized by a vertically-arranged sequence of
      ecological belts, which, in contrast to temperate habitats, have remained
      relatively stable in space across the Quaternary. Such long-lasting patterning of
      habitats makes them ideal to test the role of environmental pressure in driving
      ecological and evolutionary processes. Using Sumatran freshwater mayfly
      communities, we test whether elevation, rather than other spatial factors (i.e.
      volcanoes, watersheds) structures both species within communities and genes
      within species. Based on the analysis of 31 mayfly (Ephemeroptera) communities
      and restriction-site-associated-DNA sequencing in the four most ubiquitous
      species, we found elevation as the major spatial component structuring both
      species and genes in the landscape. In other words, similar elevations across
      different mountains or watersheds harbor more similar species and genes than
      different elevations within the same mountain or watershed. Tropical elevation
      gradients characterized by environmental conditions that are both steep and
      relatively stable seasonally and over geological time scales, are thus
      responsible for both ecological and genetic differentiation. Our results
      demonstrate how in situ ecological diversification at the micro-evolutionary
      level might fuel alpha- and beta- components of diversity in tropical sky
      islands.

PMID- 29170523
TI  - Stochastic evolutionary voluntary public goods game with punishment in a Quasi
      birth-and-death process.
AB  - Traditional replication dynamic model and the corresponding concept of
      evolutionary stable strategy (ESS) only takes into account whether the system can
      return to the equilibrium after being subjected to a small disturbance. In the
      real world, due to continuous noise, the ESS of the system may not be
      stochastically stable. In this paper, a model of voluntary public goods game with
      punishment is studied in a stochastic situation. Unlike the existing model, we
      describe the evolutionary process of strategies in the population as a
      generalized quasi-birth-and-death process. And we investigate the stochastic
      stable equilibrium (SSE) instead. By numerical experiments, we get all possible
      SSEs of the system for any combination of parameters, and investigate the
      influence of parameters on the probabilities of the system to select different
      equilibriums. It is found that in the stochastic situation, the introduction of
      the punishment and non-participation strategies can change the evolutionary
      dynamics of the system and equilibrium of the game. There is a large range of
      parameters that the system selects the cooperative states as its SSE with a high
      probability. This result provides us an insight and control method for the
      evolution of cooperation in the public goods game in stochastic situations.

PMID- 29170524
TI  - Quantitative analysis of motor evoked potentials in the neonatal lamb.
AB  - Evoking motor potentials are an objective assessment method for neuromotor
      function, yet this was to our knowledge never done in neonatal lambs. There is
      neither a method for standardized quantification of motor evoked potentials
      (MEPs). We first aimed to evaluate the feasibility of MEP recording in neonatal
      lambs and test its validity. Second we aimed to develop an algorithm for its
      quantification and test its reliability since manual input is required. We
      recorded myogenic MEPs after transcranial motor cortex stimulation in 6 lambs
      aged 1-2 days. MEPs were also measured in one lamb undergoing Neuro-Muscular
      Blockade (NMB) and another undergoing lumbar spinal cord (SC) transection, both
      serving as controls. We computed 5 parameters using a custom-made algorithm:
      motor threshold, latency, area-under-the-curve, peak-to-peak amplitude and
      duration. Intra- and inter-observer reliability was analyzed. MEPs could be
      easily recorded, disappearing after NMB and SC transection. The algorithm allowed
      for analysis, hence physiologic readings of the parameters in all 4 limbs of all
      lambs were obtained. Our method was shown to have high intra- and inter-observer
      ( >=70%) reliability for latency, area-under-the-curve and peak-to-peak
      amplitude. These results suggest that standardized MEP recording and analysis in
      neonatal lambs is feasible, and can reliably assess neuromotor function.

PMID- 29170525
TI  - Advanced glycation endproducts link inflammatory cues to upregulation of galectin
      1 in diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is an inflammatory and progressive vaso-occlusive
      disease resulting in angiogenesis. Galectin-1 is a hypoxia-induced angiogenic
      factor associated with cancer and proliferative DR. Here we reveal a significant
      upregulation of galectin-1 in eyes of DR patients along with progression of
      clinical stages beginning from the pre-ischemic, inflammatory stage with diabetic
      macular edema, but not in eyes with non-diabetic retinal vascular occlusions. As
      for its regulatory mechanism unrelated to hypoxia but selective to DR, in vitro
      galectin-1/LGALS1 expression was shown to increase after application to Muller
      glial cells with interleukin (IL)-1beta, which was induced in monocyte-derived
      macrophages and microglial cells via toll-like receptor (TLR) 4 signaling
      stimulated by advanced glycation endproducts (AGE). In vivo inhibition of AGE
      generation with aminoguanidine, macrophage depletion with clodronate liposomes,
      and antibody-based blockade of Il-1beta and Tlr4 attenuated diabetes-induced
      retinal Lgals1 expression in mice. Fibrovascular tissues from proliferative DR
      eyes were immunoreactive for AGE, TRL4 and IL-1beta in macrophages, and IL-1beta
      receptor-positive glial cells expressed galectin-1. Therefore, diabetes-induced
      retinal AGE accumulation was suggested to activate IL-1beta-related inflammatory
      cues in macrophages followed by Muller cells, linking to galectin-1 upregulation
      in human DR with time. Our data highlight AGE-triggered inflammation as the DR
      selective inducer of galectin-1.

PMID- 29170526
TI  - Driver pattern identification over the gene co-expression of drug response in
      ovarian cancer by integrating high throughput genomics data.
AB  - Multiple types of high throughput genomics data create a potential opportunity to
      identify driver patterns in ovarian cancer, which will acquire some novel and
      clinical biomarkers for appropriate diagnosis and treatment to cancer patients.
      To identify candidate driver genes and the corresponding driving patterns for
      resistant and sensitive tumors from the heterogeneous data, we combined gene co
      expression modules with mutation modulators and proposed the method to identify
      driver patterns. Firstly, co-expression network analysis is applied to explore
      gene modules for gene expression profiles through weighted correlation network
      analysis (WGCNA). Secondly, mutation matrix is generated by integrating the CNV
      data and somatic mutation data, and a mutation network is constructed from the
      mutation matrix. Thirdly, candidate modulators are selected from significant
      genes by clustering vertexs of the mutation network. Finally, a regression tree
      model is utilized for module network learning, in which the obtained gene modules
      and candidate modulators are trained for the driving pattern identification and
      modulators regulatory exploration. Many identified candidate modulators are known
      to be involved in biological meaningful processes associated with ovarian cancer,
      such as CCL11, CCL16, CCL18, CCL23, CCL8, CCL5, APOB, BRCA1, SLC18A1, FGF22,
      GADD45B, GNA15, GNA11, and so on.

PMID- 29170527
TI  - Theoretical investigations on microwave Fano resonances in 3D-printable hollow
      dielectric resonators.
AB  - High-index dielectric structures have recently been studied intensively for Mie
      resonances at optical frequencies. These dielectric structures can enable extreme
      light manipulation, similar to that which has been achieved with plasmonic
      nanostructures. In the microwave region, dielectric resonators and metamaterials
      can be fabricated directly using 3D printing, which is advantageous for
      fabricating structurally complicated 3D geometries. It is therefore especially
      suitable for the fabrication of subwavelength structures. Here we report
      theoretical investigations on microwave Fano resonances in 3D-printable
      dielectric materials and structures. In particular, we propose and analyse 3D
      printable, hollow, dielectric resonators with relatively low refractive indices,
      which exhibit sharp Fano resonances. We can control the interaction between
      bright and dark modes in a coupled dielectric particle pair by adjusting the
      inner-hole size, and thus we can increase the radiative Q factors further. We
      also find that Fano resonances in these hollow dielectric resonators are very
      sensitive to an index change in the surrounding medium, which could be useful for
      long-distance environmental sensing. New possibilities and opportunities are
      opening up with the rapid development of 3D-printing technologies. Our findings
      and the detailed investigations reported here can provide useful guidelines for
      future photonic devices based on 3D-printable materials and structures.

PMID- 29170528
TI  - Kidney Androgen-Regulated Protein (KAP) Transgenic Mice Are Protected Against
      High-Fat Diet Induced Metabolic Syndrome.
AB  - Metabolic Syndrome (MS) is reaching epidemic proportions with significant social
      and economical burden worldwide. Since the molecular basis of MS remains poorly
      defined, we investigated the impact of KAP, a kidney specific androgen-regulated
      gene, in the development of high fat-diet (hfd)-induced MS. Tg mice
      overexpressing KAP specifically in proximal tubule cells of the kidney exhibited
      reduced body weight and lower liver and adipose tissue weight compared to control
      littermates when fed a hfd. KAP Tg mice showed diminished adipocyte hypertrophy
      and reduced hepatic steatosis, significantly correlating with expression of
      relevant molecular markers and lower lipid content in liver. KAP transgenic were
      protected from hfd-induced insulin resistance, increased blood pressure and
      exhibited lower IL-6 serum levels and diminished expression of inflammatory
      markers in the adipose. Moreover, KAP was localized in the secretory pathway of
      proximal tubule cells and it is released to the extracellular media, preventing
      IL-6 induction and STAT-3 activation upon TNFalpha stimulation. We conclude that
      KAP, which might act as a hormone-like product in extra-renal tissues, protects
      Tg mice against hfd-induced MS by preventing inflammatory related events that are
      mediated, in part, through the IL-6 pathway.

PMID- 29170529
TI  - Visual analysis of mass cytometry data by hierarchical stochastic neighbour
      embedding reveals rare cell types.
AB  - Mass cytometry allows high-resolution dissection of the cellular composition of
      the immune system. However, the high-dimensionality, large size, and non-linear
      structure of the data poses considerable challenges for the data analysis. In
      particular, dimensionality reduction-based techniques like t-SNE offer single
      cell resolution but are limited in the number of cells that can be analyzed. Here
      we introduce Hierarchical Stochastic Neighbor Embedding (HSNE) for the analysis
      of mass cytometry data sets. HSNE constructs a hierarchy of non-linear
      similarities that can be interactively explored with a stepwise increase in
      detail up to the single-cell level. We apply HSNE to a study on gastrointestinal
      disorders and three other available mass cytometry data sets. We find that HSNE
      efficiently replicates previous observations and identifies rare cell populations
      that were previously missed due to downsampling. Thus, HSNE removes the
      scalability limit of conventional t-SNE analysis, a feature that makes it highly
      suitable for the analysis of massive high-dimensional data sets.

PMID- 29170530
TI  - Identification and analysis of seven effector protein families with different
      adaptive and evolutionary histories in plant-associated members of the
      Xanthomonadaceae.
AB  - The Xanthomonadaceae family consists of species of non-pathogenic and pathogenic
      gamma-proteobacteria that infect different hosts, including humans and plants. In
      this study, we performed a comparative analysis using 69 fully sequenced genomes
      belonging to this family, with a focus on identifying proteins enriched in
      phytopathogens that could explain the lifestyle and the ability to infect plants.
      Using a computational approach, we identified seven phytopathogen-enriched
      protein families putatively secreted by type II secretory system: PheA (CM-sec),
      LipA/LesA, VirK, and four families involved in N-glycan degradation, NixE, NixF,
      NixL, and FucA1. In silico and phylogenetic analyses of these protein families
      revealed they all have orthologs in other phytopathogenic or symbiotic bacteria,
      and are involved in the modulation and evasion of the immune system. As a proof
      of concept, we performed a biochemical characterization of LipA from Xac306 and
      verified that the mutant strain lost most of its lipase and esterase activities
      and displayed reduced virulence in citrus. Since this study includes closely
      related organisms with distinct lifestyles and highlights proteins directly
      related to adaptation inside plant tissues, novel approaches might use these
      proteins as biotechnological targets for disease control, and contribute to our
      understanding of the coevolution of plant-associated bacteria.

PMID- 29170532
TI  - Active Sites of M(IV)-incorporated Zeolites (M = Sn, Ti, Ge, Zr).
AB  - M(IV)-incorporated zeolites have recently aroused wide interest due to
      outstanding catalytic effects while their active sites remain largely elusive.
      Here periodic density functional theory calculations are conducted finding that
      active sites are determined jointly by identity of M(IV) ions, topology of
      zeolites, type of framework species and choice of T sites. All M2(IV) active
      sites in BEA zeolites are penta-coordinated with chemisorption of one water while
      subsequent water molecules that form only H-bonds promote chemisorption of the
      first water, especially the second water possessing comparable or even higher
      adsorption strengths as the first water; Ti(IV) and Ge(IV) active sites at the
      intersection remain penta-coordinated and Sn(IV) and Zr(IV) active sites prefer
      to hexa-coordination although potentially expanded to hepta-coordination.
      Different from other zeolites, Ti(IV) active sites in FER zeolites are hexa
      coordinated as Sn(IV) active sites, due to the promoting effect of the first
      water. Lewis acidic defects expand Ti(IV) active sites to hexa-coordination while
      inhibit the formation of hepta-coordinated Sn(IV) species. Two forms of
      Brphinsted acidic defects exist for Sn(IV) sites instead of only one for Ti(IV)
      sites, and all M(IV) Brphinsted acidic defects, regardless of different acidic
      forms and M(IV) ions, can chemisorb only one water.

PMID- 29170531
TI  - Analysis of the respiratory component of heart rate variability in the Cururu
      toad Rhinella schneideri.
AB  - Beat-to-beat variation in heart rate (f H ) has been used as a tool for
      elucidating the balance between sympathetic and parasympathetic modulation of the
      heart. A portion of the temporal changes in f H is evidenced by a respiratory
      influence (cardiorespiratory interaction) on heart rate variability (HRV) with
      heartbeats increasing and decreasing within a respiratory cycle. Nevertheless,
      little is known about respiratory effects on HRV in lower vertebrates. By using
      frequency domain analysis, we provide the first evidence of a ventilatory
      component in HRV similar to mammalian respiratory sinus arrhythmia in an
      amphibian, the toad Rhinella schneideri. Increases in the heartbeats arose
      synchronously with each lung inflation cycle, an intermittent breathing pattern
      comprised of a series of successive lung inflations. A well-marked peak in the
      HRV signal matching lung inflation cycle was verified in toads whenever lung
      inflation cycles exhibit a regular rhythm. The cardiac beat-to-beat variation
      evoked at the moment of lung inflation accounts for both vagal and sympathetic
      influences. This cardiorespiratory interaction may arise from interactions
      between central and peripheral feedback mechanisms governing cardiorespiratory
      control and may underlie important cardiorespiratory adjustments for gas exchange
      improvement especially under extreme conditions like low oxygen availability.

PMID- 29170533
TI  - Equilibrium folding dynamics of meACP in water, heavy water, and low
      concentration of urea.
AB  - Many proteins fold in apparent two-state behavior, as partially folded
      intermediates only transiently accumulate and easily escape detection. Besides a
      native form and a mainly unfolded form, we captured a partially unfolded form of
      an acyl carrier protein from Micromonospora echinospora (meACP) in the
      folding/unfolding equilibrium using chemical exchange saturation transfer NMR
      experiments. The C-terminal region of the partially unfolded form is mainly
      folded and the N-terminal is unfolded. Furthermore, to understand how the folding
      process of meACP is influenced by solvent environments, we compared the folding
      dynamics of meACP in D2O, H2O and low concentration of urea. As the environment
      becomes more denaturing from D2O to H2O and then to urea, the unfolded state
      becomes increasingly populated, and the folding rate decreases. Adding a small
      amount of urea, which does not change solvent viscosity, has little effects on
      the unfolding rates, while changing H2O to D2O reduces the unfolding rates
      possibly due to the increase of solvent viscosity. The quantified solvent effects
      on the protein folding Gibbs energy and activation energy suggest that the
      transition state of folding may have a similar structure to the native state of
      the protein.

PMID- 29170534
TI  - Increased serum vascular endothelial growth factor is associated with acute viral
      encephalitis in Bangladeshi children.
AB  - Encephalitis causes significant global morbidity and mortality. A large number of
      viruses cause encephalitis, and their geographic and temporal distributions vary.
      In many encephalitis cases, the virus cannot be detected, even after extensive
      testing. This is one challenge in management of the encephalitis patient. Since
      cytokines are pivotal in any form of inflammation and vary according to the
      nature of the inflammation, we hypothesized cytokine levels would allow us to
      discriminate between encephalitis caused by viruses and other aetiologies. This
      pilot study was conducted in a tertiary care hospital in Dhaka, Bangladesh. Viral
      detection was performed by polymerase chain reaction using patient cerebrospinal
      fluid. Acute phase reactants and cytokines were detected in patient serum. Of the
      29 biomarkers assessed using the Wilcoxon rank-sum test, only vascular
      endothelial growth factor (VEGF) was significantly higher (P = 0.0015) in viral
      positive compared with virus-negative encephalitis patients. The area under the
      curve (AUC) for VEGF was 0.82 (95% confidence interval: 0.66-0.98). Serum VEGF
      may discriminate between virus-positive and virus-negative encephalitis. Further
      study will be needed to confirm these findings.

PMID- 29170535
TI  - Rapid Detection of Prunus Necrotic Ringspot Virus by Reverse Transcription-cross
      priming Amplification Coupled with Nucleic Acid Test Strip Cassette.
AB  - Prunus necrotic ringspot virus (PNRSV) is one of the most devastating viruses to
      Prunus spp. In this study, we developed a diagnostic system RT-CPA-NATSC, wherein
      reverse transcription-cross-priming amplification (RT-CPA) is coupled with
      nucleic acid test strip cassette (NATSC), a vertical flow (VF) visualization, for
      PNRSV detection. The RT-CPA-NATSC assay targets the encoding gene of the PNRSV
      coat protein with a limit of detection of 72 copies per reaction and no cross
      reaction with the known Prunus pathogenic viruses and viroids, demonstrating high
      sensitivity and specificity. The reaction is performed on 60  degrees C and can
      be completed less than 90 min with the prepared template RNA. Field sample test
      confirmed the reliability of RT-CPA-NATSC, indicating the potential application
      of this simple and rapid detection method in routine test of PNRSV.

PMID- 29170538
TI  - Diabetes: Very-low-calorie diet reverses T2DM in rats.

PMID- 29170539
TI  - Adipose tissue: Noncanonical beige fat thermogenesis.

PMID- 29170536
TI  - Non-coding RNA networks in cancer.
AB  - Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work
      from the past decade has altered our perception of ncRNAs from 'junk'
      transcriptional products to functional regulatory molecules that mediate cellular
      processes including chromatin remodelling, transcription, post-transcriptional
      modifications and signal transduction. The networks in which ncRNAs engage can
      influence numerous molecular targets to drive specific cell biological responses
      and fates. Consequently, ncRNAs act as key regulators of physiological programmes
      in developmental and disease contexts. Particularly relevant in cancer, ncRNAs
      have been identified as oncogenic drivers and tumour suppressors in every major
      cancer type. Thus, a deeper understanding of the complex networks of interactions
      that ncRNAs coordinate would provide a unique opportunity to design better
      therapeutic interventions.

PMID- 29170537
TI  - Hippocampal MRS and subfield volumetry at 7T detects dysfunction not specific to
      seizure focus.
AB  - Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in
      temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with
      normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal
      subfield atrophy and deviations in brain metabolites characterize epileptic
      hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched
      healthy volunteers were scanned at 7T. Hippocampal subfields were manually
      segmented from 600MUm isotropic resolution susceptibility-weighted images.
      Hippocampal metabolite spectra were acquired to determine absolute concentrations
      of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed
      case-controls analyses, using permutation testing, to identify abnormalities in
      hippocampal imaging measures in individual patients, for evaluation against
      clinical evidence of seizure lateralisation and neuropsychological memory test
      scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients
      (75%), commonly affecting CA3. 7/8 patients had altered metabolite
      concentrations, most showing reduced glutamine levels (62.5%). However, neither
      volume nor metabolite deviations consistently lateralized the epileptogenic
      hippocampus. Rather, lower subiculum volumes and glutamine concentrations
      correlated with impaired verbal memory performance. Hippocampal subfield and
      metabolic abnormalities detected at 7T appear to reflect pathophysiological
      processes beyond epileptogenesis. Despite limited diagnostic contributions, these
      markers show promise to help elucidate mnemonic processing in TLE.

PMID- 29170541
TI  - Thyroid cancer: CAR T cell therapy - potential in advanced thyroid cancer?

PMID- 29170540
TI  - Obesity: Trends in underweight and obesity - scale of the problem.

PMID- 29170542
TI  - Diabetes: Metformin - a cardiovascular moderator of DPP4 inhibitors?

PMID- 29170544
TI  - Structural, electronic, magnetic, half-metallic, mechanical, and thermodynamic
      properties of the quaternary Heusler compound FeCrRuSi: A first-principles study.
AB  - In this paper, we have investigated the structural, electronic, magnetic, half
      metallic, mechanical, and thermodynamic properties of the equiatomic quaternary
      Heusler (EQH) compound FeCrRuSi using the density functional theory (DFT) and the
      quasi-harmonic Debye model. Our results reveal that FeCrRuSi is a half-metallic
      material (HMM) with a total magnetic moment of 2.0 MUB in agreement with the well
      known Slater-Pauling rule Mt = Zt - 24. Furthermore, the origin of the half
      metallic band gap in FeCrRuSi is well studied through a schematic diagram of the
      possible d-d hybridization between Fe, Cr and Ru elements. The half-metallic
      behavior of FeCrRuSi can be maintained in a relatively wide range of variations
      of the lattice constant (5.5-5.8 A) under uniform strain and the c/a ratio (0.96
      1.05) under tetragonal distortion. The calculated phonon dispersion, cohesive and
      formation energies, and mechanical properties reveal that FeCrRuSi is stable with
      an EQH structure. Importantly, the compound of interest has been prepared and is
      found to exist in an EQH type structure with the presence of some B2 disorder.
      Moreover, the thermodynamic properties, such as the thermal expansion coefficient
      alpha, the heat capacity CV, the Gruneisen constant gamma, and the Debye
      temperature ThetaD are calculated.

PMID- 29170543
TI  - Long-term effects of adolescent obesity: time to act.
AB  - Obesity in adolescence will probably have major implications not only for the
      affected adolescents but also for society. Those who have obesity during
      adolescence usually have obesity into adulthood, which causes many medical and
      psychological issues that can result in premature death. Furthermore, obesity in
      adolescents is associated with a range of social problems, including difficulties
      securing an apprenticeship or a job or finding a partner. Adolescents with
      obesity are also at increased risk of having children with obesity later in life.
      All these consequences lead to high costs for the health-care system. Although
      efficient treatment options are available that have been proven in randomized
      controlled trials, such as lifestyle interventions for adolescents with obesity
      and bariatric surgery for adolescents with severe obesity, these interventions
      frequently fail in clinical practice as treatment adherence is low in adolescents
      and most adolescents with obesity do not seek medical care. Therefore, improving
      treatment adherence and identifying treatment barriers are necessary.

PMID- 29170545
TI  - Increased light penetration due to ultrasound-induced air bubbles in optical
      scattering media.
AB  - Light is an attractive tool for high spatial- and contrast-resolution imaging,
      highly sensitive molecular imaging, and target-selective therapy, and it does not
      exhibit the risks associated with ionizing radiation. The main limitation of
      using light in clinical applications is its superficial imaging and therapeutic
      depth caused by high optical scattering in biological media. Here, we demonstrate
      that the scattering and thus defocusing of the incident light can be alleviated
      when simultaneously delivered ultrasound generates air bubbles in the pathway of
      the incident light, thus increasing the light penetration. The bubbles are
      temporally induced by ultrasound with an intensity that is sufficiently low to
      avoid tissue damage and act as a Mie scattering medium in which light is
      scattered predominantly in the forward direction. The change in the optical
      scattering property caused by the ultrasound is undone after cessation of the
      insonification. From the results, it is expected that this proposed method will
      open a new route for overcoming the limitations of current optical imaging and
      therapeutic techniques.

PMID- 29170546
TI  - Disease models: Method in the madness of fibrosis.

PMID- 29170547
TI  - 2D materials: Curved paths of electron-hole pairs.

PMID- 29170548
TI  - Beating the thermodynamic limit with photo-activation of n-doping in organic
      semiconductors.
AB  - Chemical doping of organic semiconductors using molecular dopants plays a key
      role in the fabrication of efficient organic electronic devices. Although a
      variety of stable molecular p-dopants have been developed and successfully
      deployed in devices in the past decade, air-stable molecular n-dopants suitable
      for materials with low electron affinity are still elusive. Here we demonstrate
      that photo-activation of a cleavable air-stable dimeric dopant can result in
      kinetically stable and efficient n-doping of host semiconductors, whose reduction
      potentials are beyond the thermodynamic reach of the dimer's effective reducing
      strength. Electron-transport layers doped in this manner are used to fabricate
      high-efficiency organic light-emitting diodes. Our strategy thus enables a new
      paradigm for using air-stable molecular dopants to improve conductivity in, and
      provide ohmic contacts to, organic semiconductors with very low electron
      affinity.

PMID- 29170549
TI  - Designer biomaterials for mechanobiology.

PMID- 29170550
TI  - Corrigendum: Strong, tough and stiff bioinspired ceramics from brittle
      constituents.
AB  - This corrects the article DOI: 10.1038/nmat3915.

PMID- 29170551
TI  - Material witness: Who made the first glass?

PMID- 29170552
TI  - Cellular adhesion: Instant integrin mechanosensing.

PMID- 29170553
TI  - Matrix degradation: Making way for neural stemness.

PMID- 29170555
TI  - Regeneration gets physical.

PMID- 29170554
TI  - Mechanotransduction-modulated fibrotic microniches reveal the contribution of
      angiogenesis in liver fibrosis.
AB  - The role of pathological angiogenesis on liver fibrogenesis is still unknown.
      Here, we developed fibrotic microniches (FMUNs) that recapitulate the interaction
      of liver sinusoid endothelial cells (LSECs) and hepatic stellate cells (HSCs). We
      investigated how the mechanical properties of their substrates affect the
      formation of capillary-like structures and how they relate to the progression of
      angiogenesis during liver fibrosis. Differences in cell response in the FMUNs
      were synonymous of the early and late stages of liver fibrosis. The stiffness of
      the early-stage FMUNs was significantly elevated due to condensation of collagen
      fibrils induced by angiogenesis, and led to activation of HSCs by LSECs. We
      utilized these FMUNs to understand the response to anti-angiogenic drugs, and it
      was evident that these drugs were effective only for early-stage liver fibrosis
      in vitro and in an in vivo mouse model of liver fibrosis. Late-stage liver
      fibrosis was not reversed following treatment with anti-angiogenic drugs but
      rather with inhibitors of collagen condensation. Our work reveals stage-specific
      angiogenesis-induced liver fibrogenesis via a previously unrevealed
      mechanotransduction mechanism which may offer precise intervention strategies
      targeting stage-specific disease progression.

PMID- 29170556
TI  - Ultrathin graphene-based membrane with precise molecular sieving and ultrafast
      solvent permeation.
AB  - Graphene oxide (GO) membranes continue to attract intense interest due to their
      unique molecular sieving properties combined with fast permeation. However, their
      use is limited to aqueous solutions because GO membranes appear impermeable to
      organic solvents, a phenomenon not yet fully understood. Here, we report
      efficient and fast filtration of organic solutions through GO laminates
      containing smooth two-dimensional (2D) capillaries made from large (10-20 MUm)
      flakes. Without modification of sieving characteristics, these membranes can be
      made exceptionally thin, down to ~10 nm, which translates into fast water and
      organic solvent permeation. We attribute organic solvent permeation and sieving
      properties to randomly distributed pinholes interconnected by short graphene
      channels with a width of 1 nm. With increasing membrane thickness, organic
      solvent permeation rates decay exponentially but water continues to permeate
      quickly, in agreement with previous reports. The potential of ultrathin GO
      laminates for organic solvent nanofiltration is demonstrated by showing >99.9%
      rejection of small molecular weight organic dyes dissolved in methanol. Our work
      significantly expands possibilities for the use of GO membranes in purification
      and filtration technologies.

PMID- 29170557
TI  - Corrigendum: Generation of subnanometric platinum with high stability during
      transformation of a 2D zeolite into 3D.
AB  - This corrects the article DOI: 10.1038/nmat4757.

PMID- 29170559
TI  - Addendum: Magnetically assisted slip casting of bioinspired heterogeneous
      composites.
AB  - This corrects the article DOI: 10.1038/nmat4419.

PMID- 29170558
TI  - Leveraging advances in biology to design biomaterials.
AB  - Biomaterials have dramatically increased in functionality and complexity,
      allowing unprecedented control over the cells that interact with them. From these
      engineering advances arises the prospect of improved biomaterial-based therapies,
      yet practical constraints favour simplicity. Tools from the biology community are
      enabling high-resolution and high-throughput bioassays that, if incorporated into
      a biomaterial design framework, could help achieve unprecedented functionality
      while minimizing the complexity of designs by identifying the most important
      material parameters and biological outputs. However, to avoid data explosions and
      to effectively match the information content of an assay with the goal of the
      experiment, material screens and bioassays must be arranged in specific ways. By
      borrowing methods to design experiments and workflows from the bioprocess
      engineering community, we outline a framework for the incorporation of next
      generation bioassays into biomaterials design to effectively optimize function
      while minimizing complexity. This framework can inspire biomaterials designs that
      maximize functionality and translatability.

PMID- 29170560
TI  - Clinicopathological correlation of tumor-associated macrophages in Ewing sarcoma.
AB  - AIMS: Tumor-associated macrophages (TAMs) are known markers playing complex roles
      in tumorigenesis. However, the function of TAMs in a variety of malignancies is
      not yet fully understood. The aim of this pilot study was to quantify the density
      of TAMs in Ewing sarcoma and to determine the correlation between TAMs and
      clinicopathological parameters. METHODS: Using immunohistochemistry, the
      expressions of CD68 and CD163 were examined in 24 tissue samples of Ewing sarcoma
      of bone. The density of CD68 and CD163-positive TAMs was analyzed quantitatively
      and semi-quantitatively and statistically correlated with clinical parameters.
      RESULTS: CD163-positive TAMs outnumbered CD68-positive cells (median of 130 vs
      96, respectively). No statistically significant relatio nship was found between
      density of CD68-positive cells, clinical parameters or prognosis. However, high
      levels of CD163-positive TAMs were associated with localized disease (P=0.008).
      In cases with a higher density of CD163-positive cells, a trend toward longer
      survival was revealed (P=0.063). CONCLUSION: This is the first study that has
      quantified CD163 expression in TAMs in Ewing sarcoma and showed its possible
      prognostic value. CD163 was confirmed to be a more specific marker of macrophages
      than CD68. CD163 is not an exclusive hallmark of M2 macrophages.

PMID- 29170561
TI  - Choice Inconsistencies among the Elderly: Evidence from Plan Choice in the
      Medicare Part D Program: Reply.
AB  - We explore the in- and out- of sample robustness of tests for choice
      inconsistencies based on parameter restrictions in parametric models, focusing on
      tests proposed by Ketcham, Kuminoff and Powers (KKP). We argue that their non
      parametric alternatives are inherently conservative with respect to detecting
      mistakes. We then show that our parametric model is robust to KKP's suggested
      specification checks, and that comprehensive goodness of fit measures perform
      better with our model than the expected utility model. Finally, we explore the
      robustness of our 2011 results to alternative normative assumptions highlighting
      the role of brand fixed effects and unobservable characteristics.

PMID- 29170562
TI  - Enhanced durability of carbon nanotube grafted hierarchical ceramic microfiber
      reinforced epoxy composites.
AB  - As carbon nanotube (CNT) infused hybrid composites are increasingly identified as
      next-generation aerospace materials, it is vital to evaluate their long-term
      structural performance under aging environments. In this work, the durability of
      hierarchical, aligned CNT grafted aluminoborosilicate microfiber-epoxy composites
      (CNT composites) are compared against baseline aluminoborosilicate composites
      (baseline composites), before and after immersion in water at 25  degrees C
      (hydro) and 60  degrees C (hydrothermal), for extended durations (90 d and 180
      d). The addition of CNTs is found to reduce water diffusivities by approximately
      1.5 times. The mechanical properties (bending strength and modulus) and the
      damage sensing capabilities (DC conductivity) of CNT composites remain intact
      regardless of exposure conditions. The baseline composites show significant loss
      of strength (44 %) after only 15 d of hydrothermal aging. This loss of mechanical
      strength is attributed to fiber-polymer interfacial debonding caused by
      accumulation of water at high temperatures. In situ acoustic and DC electrical
      measurements of hydrothermally aged CNT composites identify extensive stress
      relieving micro-cracking and crack deflections that are absent in the aged
      baseline composites. These observations are supported by SEM images of the failed
      composite cross-sections that highlight secondary matrix toughening mechanisms in
      the form of CNT pullouts and fractures which enhance the service life of
      composites and maintain their properties under accelerated aging environments.

PMID- 29170563
TI  - CE Separation and ICP-MS Detection of Gold Nanoparticles and Their Protein
      Conjugates.
AB  - A full understanding and mediation of nanoparticle-serum protein interactions is
      key to design nanoparticles with vivid functions within the body, and to solve
      this problem one needs to differentiate and characterize individual nano-protein
      conjugates. In this paper, the authors applied capillary electrophoresis combined
      with inductively coupled plasma mass spectrometry detection to study the behavior
      of gold nanoparticles of different geometry, size and surface functionalization
      upon interacting with serum proteins and their mixtures. Due to high-resolution
      and -sensitivity benefits of this combined technique baseline separations were
      attained for free nanoparticles (at real-life doses) and different protein
      conjugates, and the conversion into the protein-bound form was scrutinized in
      terms of reaction time.

PMID- 29170564
TI  - INTEGRATED MICROFLUIDIC SELEX USING FREE SOLUTION ELECTROKINETICS.
AB  - Systematic evolution of ligands by exponential enrichment (SELEX) offers a
      powerful method to isolate affinity oligonucleotides known as aptamers, which can
      then be used in a wide range of applications from drug delivery to biosensing.
      However, conventional SELEX methods rely on labor intensive and time consuming
      benchtop operations. A simplified microfluidic approach is presented which allows
      integration of the affinity selection and amplification stages of SELEX for the
      isolation of target-binding oligonucleotides by combining bead-based biochemical
      reactions with free solution electrokinetic oligonucleotide transfer. Free
      solution electrokinetics allows coupling of affinity selection and amplification
      for closed loop oligonucleotide enrichment without the need for offline
      processes, flow handling components or gel components, while bead based selection
      and amplification allow efficient manipulation of reagents and reaction products
      thereby realizing on-chip loop closure and integration of the entire SELEX
      process. Thus the approach is capable of multi-round enrichment of
      oligonucleotides using simple transfer processes while maintaining a high level
      of device integration, as demonstrated by the isolation of an aptamer pool
      against a protein target (IgA) with significantly higher binding affinity than
      the starting library in approximately 4 hours of processing time.

PMID- 29170565
TI  - Behavior Problems in Elementary School among Low-Income Males: The Role of
      Teacher-Child Relationships.
AB  - The present study identified trajectories of teacher-child relationship conflict
      and closeness from first through sixth grades, and associations between these
      trajectories and externalizing and internalizing behaviors at age 11 among low
      income, urban males (N = 262). There were three main findings. Nagin cluster
      analyses indicated five trajectories for conflict with all children evidencing
      increases in conflict, and four trajectories for closeness with all children
      demonstrating decreases in closeness. Trajectories with higher levels of conflict
      and lower levels of closeness were associated with higher levels of externalizing
      and internalizing behavior problems at age 11. Moreover, conflictual teacher
      child relationships exacerbated the effects of externalizing and internalizing
      behavior problems in early childhood; children with conflictual teacher-child
      relationships had higher levels of behavior problems in middle childhood relative
      to children with low conflictual teacher-child relationships. Implications of
      targeting teacher-child relationships as interventions to help prevent behavior
      problems are discussed.

PMID- 29170566
TI  - What reduces sexual minority stress? A review of the intervention "toolkit".
AB  - Sexual orientation health disparities are rooted in sexual minorities' exposure
      to stress and challenges to effective coping. This paper reviews the "toolkit" of
      psychosocial interventions available to reduce sexual minority stress effects. A
      systematic search uncovered 44 interventions that both seek to reduce sexual
      minority stress at its source in unjust and discriminatory social structures as
      well as bolster sexual minorities' stigma-coping abilities. These interventions
      were implemented in a variety of contexts (e.g., education, health care delivery)
      and utilized heterogeneous modalities to create change (e.g., policy
      implementation, role-playing activities). They were designed to affect change
      across structural, interpersonal, and individual levels. The interventions
      reviewed here, while in early stages of efficacy testing, possess potential for
      meeting the needs and resources of mental and medical health care providers,
      policy makers, and other stakeholders who aim to lessen the burden of sexual
      minority stress and the health disparities it generates.

PMID- 29170567
TI  - Predicting ecological responses in a changing ocean: the effects of future
      climate uncertainty.
AB  - Predicting how species will respond to climate change is a growing field in
      marine ecology, yet knowledge of how to incorporate the uncertainty from future
      climate data into these predictions remains a significant challenge. To help
      overcome it, this review separates climate uncertainty into its three components
      (scenario uncertainty, model uncertainty, and internal model variability) and
      identifies four criteria that constitute a thorough interpretation of an
      ecological response to climate change in relation to these parts (awareness,
      access, incorporation, communication). Through a literature review, the extent to
      which the marine ecology community has addressed these criteria in their
      predictions was assessed. Despite a high awareness of climate uncertainty,
      articles favoured the most severe emission scenario, and only a subset of climate
      models were used as input into ecological analyses. In the case of sea surface
      temperature, these models can have projections unrepresentative against a larger
      ensemble mean. Moreover, 91% of studies failed to incorporate the internal
      variability of a climate model into results. We explored the influence that the
      choice of emission scenario, climate model, and model realisation can have when
      predicting the future distribution of the pelagic fish, Electrona antarctica.
      Future distributions were highly influenced by the choice of climate model, and
      in some cases, internal variability was important in determining the direction
      and severity of the distribution change. Increased clarity and availability of
      processed climate data would facilitate more comprehensive explorations of
      climate uncertainty, and increase in the quality and standard of marine
      prediction studies.

PMID- 29170568
TI  - Southern Ocean pteropods at risk from ocean warming and acidification.
AB  - Early life stages of marine calcifiers are particularly vulnerable to climate
      change. In the Southern Ocean aragonite undersaturation events and areas of rapid
      warming already occur and are predicted to increase in extent. Here, we present
      the first study to successfully hatch the polar pteropod Limacina helicina
      antarctica and observe the potential impact of exposure to increased temperature
      and aragonite undersaturation resulting from ocean acidification (OA) on the
      early life stage survival and shell morphology. High larval mortality (up to 39%)
      was observed in individuals exposed to perturbed conditions. Warming and OA
      induced extensive shell malformation and dissolution, respectively, increasing
      shell fragility. Furthermore, shell growth decreased, with variation between
      treatments and exposure time. Our results demonstrate that short-term exposure
      through passing through hotspots of OA and warming poses a serious threat to
      pteropod recruitment and long-term population viability.

PMID- 29170569
TI  - Fine-scale population genetic structure of sugar kelp, Saccharina latissima
      (Laminariales, Phaeophyceae), in eastern Maine, USA.
AB  - There is an interest to develop sugar kelp (Saccharina latissima) cultivation in
      the rural, eastern Maine region of the USA. Future farming efforts would benefit
      from an understanding of the genetic diversity and population structure of kelp,
      to inform management and conservation, and to identify genetic resources. The
      purpose of the present study was to characterize the fine-scale population
      genetic structure of kelp in eastern Maine, using twelve microsatellite loci. A
      total of 188 samples were genotyped from five sampling locations. Overall, kelp
      exhibited relatively low genetic diversity and small but significant
      differentiation among populations (FST = 0.0157). The greatest genetic difference
      was detected between two geographically close populations in Penobscot and
      Frenchman Bays, which is likely due to patterns in the Eastern Maine Coastal
      Current that may limit meiospore recruitment. The population structure could not
      be fully explained by an isolation-by-distance model. Fine-scale structuring was
      also detected among populations along the more continuous, eastern Maine
      coastline. These differences highlight that sugar kelp populations are finely
      structured across small spatial scales, and that future management and farming
      efforts should aim to maintain genetic diversity and assess the culture potential
      of local populations.

PMID- 29170570
TI  - Substance Use among Youth with Currently and Formerly Incarcerated Parents.
AB  - Parental incarceration impacts millions of children in the U.S. and has important
      consequences for youths' adjustment. Children of incarcerated parents are at risk
      for a host of negative psychosocial outcomes, including substance abuse problems.
      Using data from a statewide survey of youth behavior, the effect of both present
      and past parental incarceration on youths' report of their substance use
      behaviors was examined. Both present and past parental incarceration was
      significantly associated with use of alcohol, tobacco, marijuana, and
      prescription drugs, as well as substance abuse and dependence. Implications for
      practice and research are discussed.

PMID- 29170571
TI  - Reliability between online raters with varying familiarities of a region:
      Microscale Audit of Pedestrian Streetscapes (MAPS).
AB  - Background: To test inter-rater reliability of the online Microscale Audit of
      Pedestrian Streetscapes (MAPS) tool between raters with varying familiarities of
      Phoenix, Arizona. Methods: The online MAPS tool, based on the MAPS in-field audit
      tool and scoring system, was used for audits. Sixty route pairs, 141 segment
      pairs, and 92 crossing pairs in Phoenix were included. Each route, segment or
      crossing was audited by two independent raters: one rater in Phoenix and the
      other in San Diego, California, respectively. Item, subscale scores, and total
      scores reliability analyses were computed using Kappa or intra-class correlation
      coefficient (ICC). Results: The route overall score had substantial reliability
      (ICC: 0.832). Of the route subscale and overall scores, sixteen out of twenty had
      moderate to substantial reliability (ICC: 0.616-0.906), and the four subscales
      had fair reliability (ICC: 0.409-0.563). Sixteen out of twenty scores in segment
      and crossing sections demonstrated fair to substantial reliability (ICC: 0.448
      0.897), and the remaining four had slight reliability (ICC: 0.348-0.364).
      Conclusions: Most of the online MAPS items, subscales, and overall scores
      demonstrated fair to substantial reliability between raters with varied
      familiarities of the Phoenix area. Results support use of online MAPS to measure
      microscale elements of the built environment by raters unfamiliar with a region.

PMID- 29170573
TI  - Novel Pretreatments of Whole Blood Using Fenton-like Processes for Trace Metal
      Analysis.
AB  - Whole blood is a complex mixture of biological and chemical species. Its
      pretreatment, which is often conducted by dry ashing, is needed before the
      analyses of trace metals in whole blood. Recently photo-Fenton Advanced Oxidation
      Process (AOP) process has been used in the pretreatment of whole blood. Two new
      AOP processes using simple heating and microwave irradiation have been developed
      in the current work to pretreat blood samples. The treatments are based on a
      Fenton-like AOP with acid deactivation of the enzyme catalase. The first
      treatment is performed with a lab oven over 5 h, while the second uses microwave
      irradiation for 6 min. These methods allow for either cost-effective pretreatment
      through the use of the lab oven, or time savings through the use of the microwave
      oven. The degradations of blood and pure hemoglobin samples are compared through
      UV/visible spectroscopy, and the copper concentration in the treated samples were
      analyzed via anodic stripping voltammetry as a demonstration of analyzing trace
      metals in the pretreated whole blood.

PMID- 29170572
TI  - Use of Research Evidence and Implementation of Evidence-Based Practices in Youth
      Serving Systems.
AB  - Although the effectiveness of interventions for prevention and treatment of
      mental health and behavioral problems in abused and neglected youth is
      demonstrated through the accumulation of evidence through rigorous and systematic
      research, it is uncertain whether use of research evidence (URE) by child-serving
      systems leaders increases the likelihood of evidence- based practice (EBP)
      implementation and sustainment. Information on URE was collected from 151
      directors and senior administrators of child welfare, mental health and juvenile
      justice systems in 40 California and 11 Ohio counties participating in an RCT of
      the use of community development teams (CDTs) to scale up implementation of
      Treatment Foster Care Oregon over a 3 year period (2010-12). Separate
      multivariate models were used to assess independent effects of evidence
      acquisition (input), evaluation (process), application (output), and URE in
      general (SIEU Total) on two measures of EBP implementation, highest stage reached
      and proportion of activities completed at pre-implementation, implementation and
      sustainment phases. Stage of implementation and proportion of activities
      completed in the implementation and sustainment phases were independently
      associated with acquisition of evidence and URE in general. Participation in CDTs
      was significantly associated with URE in general and acquisition of research
      evidence in particular. Implementation of EBPs for treatment of abused and
      neglected youth does appear to be associated with use of research evidence,
      especially during the later phases.

PMID- 29170574
TI  - The checkpoint ordering problem.
AB  - We suggest a new variant of a row layout problem: Find an ordering of n
      departments with given lengths such that the total weighted sum of their
      distances to a given checkpoint is minimized. The Checkpoint Ordering Problem
      (COP) is both of theoretical and practical interest. It has several applications
      and is conceptually related to some well-studied combinatorial optimization
      problems, namely the Single-Row Facility Layout Problem, the Linear Ordering
      Problem and a variant of parallel machine scheduling. In this paper we study the
      complexity of the (COP) and its special cases. The general version of the (COP)
      with an arbitrary but fixed number of checkpoints is NP-hard in the weak sense.
      We propose both a dynamic programming algorithm and an integer linear programming
      approach for the (COP) . Our computational experiments indicate that the (COP) is
      hard to solve in practice. While the run time of the dynamic programming
      algorithm strongly depends on the length of the departments, the integer linear
      programming approach is able to solve instances with up to 25 departments to
      optimality.

PMID- 29170575
TI  - Tower-Based Greenhouse Gas Measurement Network Design---The National Institute of
      Standards and Technology North East Corridor Testbed.
AB  - The North-East Corridor (NEC) Testbed project is the 3rd of three NIST (National
      Institute of Standards and Technology) greenhouse gas emissions testbeds designed
      to advance greenhouse gas measurements capabilities. A design approach for a
      dense observing network combined with atmospheric inversion methodologies is
      described. The Advanced Research Weather Research and Forecasting Model with the
      Stochastic Time-Inverted Lagrangian Transport model were used to derive the
      sensitivity of hypothetical observations to surface greenhouse gas emissions
      (footprints). Unlike other network design algorithms, an iterative selection
      algorithm, based on a k-means clustering method, was applied to minimize the
      similarities between the temporal response of each site and maximize sensitivity
      to the urban emissions contribution. Once a network was selected, a synthetic
      inversion Bayesian Kalman filter was used to evaluate observing system
      performance. We present the performances of various measurement network
      configurations consisting of differing numbers of towers and tower locations.
      Results show that an overly spatially compact network has decreased spatial
      coverage, as the spatial information added per site is then suboptimal as to
      cover the largest possible area, whilst networks dispersed too broadly lose
      capabilities of constraining flux uncertainties. In addition, we explore the
      possibility of using a very high density network of lower cost and performance
      sensors characterized by larger uncertainties and temporal drift. Analysis
      convergence is faster with a large number of observing locations, reducing the
      response time of the filter. Larger uncertainties in the observations implies
      lower values of uncertainty reduction. On the other hand, the drift is a bias in
      nature, which is added to the observations and, therefore, biasing the retrieved
      fluxes.

PMID- 29170576
TI  - Early Jurassic diversification of pycnodontiform fishes (Actinopterygii,
      Neopterygii) after the end-Triassic extinction event: evidence from a new genus
      and species, Grimmenodon aureum.
AB  - A new genus and species of pycnodontiform fishes, Grimmenodon aureum, from
      marginal marine, marine-brackish lower Toarcian (Harpoceras exaratum ammonite
      subzone) clay deposits of Grimmen in northeastern Germany is described. The
      single specimen represents a diagnostic left prearticular dentition characterized
      by unique tooth arrangement and ornamentation patterns. Grimmenodon aureum, gen.
      et sp. nov., is the second unambiguously identified pycnodontiform species from
      the Early Jurassic, in addition to Eomesodon liassicus from the early Lower
      Jurassic of western Europe. We also report an indeterminate pycnodontiform tooth
      crown from the upper Pliensbachian (Pleuroceras apyrenum ammonite subzone) of the
      same site. The material expands the Early Jurassic range of pycnodontiforms
      significantly northwards and confirms their presence before and immediately
      following the onset of the Toarcian Oceanic Anoxic Event (T-OAE) in the marginal
      marine ecosystems south of the Fennoscandian Shield. Moreover, the new records
      indicate that the Early Jurassic diversity of pycnodontiform fishes was greater
      than previously assumed and probably equaled that of the Late Triassic.
      Therefore, it is hypothesized that the Triassic-Jurassic mass extinction event
      did not affect pycnodontiform fishes significantly. Micro-computed tomography was
      used to study the internal anatomy of the prearticular of Grimmenodon aureum,
      gen. et sp. nov. Our results show that no replacement teeth were formed within
      the tooth-bearing bone but rather were added posteriorly to functional teeth.
      http://zoobank.org/urn:lsid:zoobank.org:pub:A56BDE9C-40C4-4CFA-9C2E-F5FA35A66F2
      Citation for this article: Stumpf, S., J. Ansorge, C. Pfaff, and J. Kriwet. 2017.
      Early Jurassic diversification of pycnodontiform fishes (Actinopterygii,
      Neopterygii) after the end-Triassic extinction event: Evidence from a new genus
      and species, Grimmenodon aureum. Journal of Vertebrate Paleontology. DOI:
      10.1080/02724634.2017.1344679.

PMID- 29170577
TI  - Terminal NiII-OH/-OH2 complexes in trigonal bipyramidal geometries derived from
      H2O.
AB  - The preparation and characterization of two NiII complexes are described, a
      terminal NiII-OH complex with the tripodal ligand tris[(N)-tertbutylureaylato)-N
      ethyl)]aminato ([H3buea]3-) and a terminal Ni II-OH2 complex with the tripodal
      ligand N,N',N"-[2,2',2"-nitrilotris(ethane-2,1-diyl)]tris(2,4,6
      trimethylbenzenesulfonamido) ([MST]3-). For both complexes, the source of the -OH
      and -OH2 ligand is water. The salts K2[NiIIH3buea(OH)] and NMe4[NiIIMST(OH2)]
      were characterized using perpendicular-mode X-band electronic paramagnetic
      resonance, Fourier transform infrared, UV-visible spectroscopies, and its
      electrochemical properties were evaluated using cyclic voltammetry. The solid
      state structures of these complexes determined by X-ray diffraction methods
      reveal that they adopt a distorted trigonal bipyramidal geometry, an unusual
      structure for 5-coordinate NiII complexes. Moreover, the NiII-OH and NiII-OH2
      units form intramolecular hydrogen bonding networks with the [H3buea]3- and
      [MST]3- ligands. The oxidation chemistry of these complexes was explored by
      treating the high-spin NiII compounds with one-electron oxidants. Species were
      formed with S = 1/2 spin ground states that are consistent with formation of
      monomeric NiIII species. While the formation of NiIII-OH complexes cannot be
      ruled out, the lack of observable O-H vibrations from the putative Ni-OH units
      suggest the possibility that other high valent Ni species are formed.

PMID- 29170578
TI  - Investigating Changes in Resting-State Connectivity from Functional MRI Data in
      Patients with HIV Associated Neurocognitive Disorder Using MCA and Machine
      Learning.
AB  - Infection of the brain by the Human Immunodeficiency Virus (HIV) causes
      irreversible damage to the synaptic connections resulting in cognitive
      impairment. Patients with HIV infection, showing signs of impairment in multiple
      cognitive domains, as assessed by neuropsychological testing, are said to exhibit
      symptoms of HIV Associated Neurocognitive Disorder (HAND). In this study, we use
      resting-state functional MRI (fMRI) data to distinguish between healthy subjects
      and subjects with symptoms of HAND. To this end, we first establish a measure of
      interaction between pairs of regional time-series by quantifying their non-linear
      functional connectivity using Mutual Connectivity Analysis (MCA). Subsequently,
      we use a classifier to distinguish patterns of interaction between healthy and
      diseased individuals. Our results, quantified as the mean Area under the ROC
      curve (AUC) over 75 iterations, indicate that, using fMRI data, we can
      discriminate between the two cohorts well (AUC > 0.8). Specifically, we find that
      MCA (mean AUC = 0.89) based connectivity features perform significantly better (p
      < 0.05) when compared to cross-correlation (mean AUC = 0.82) at the
      classification task. A higher AUC using our approach suggests that such a
      nonlinear approach is better able to capture connectivity changes between brain
      regions and has potential for the development of novel neuro-imaging biomarkers.

PMID- 29170579
TI  - Predicting the Biomechanical Strength of Proximal Femur Specimens through High
      Dimensional Geometric Features and Support Vector Regression.
AB  - Estimating local trabecular bone quality for purposes of femoral bone strength
      prediction is important for improving the clinical assessment of osteoporotic hip
      fracture risk. In this study, we explore the ability of geometric features
      derived from the Scaling Index Method (SIM) in predicting the biomechanical
      strength of proximal femur specimens as visualized on multi-detector computed
      tomography (MDCT) images. MDCT scans were acquired for 50 proximal femur
      specimens harvested from human cadavers. An automated volume of interest (VOI)
      fitting algorithm was used to define a consistent volume in the femoral head of
      each specimen. In these VOIs, the non-linear micro-structure of the trabecular
      bone was characterized by statistical moments of its BMD distribution and by
      local scaling properties derived from SIM. Linear multi-regression analysis and
      support vector regression with a linear kernel (SVRlin) were used to predict the
      failure load (FL) from the feature sets; the predicted FL was compared to the FL
      values determined through biomechanical testing. The prediction performance was
      measured by the root mean square error (RMSE) for each image feature on
      independent test set. The best prediction result was obtained from the SIM
      feature set with SVRlin, which had the lowest prediction error (RMSE = 0.842 +/-
      0.209) and which was significantly lower than the conventionally used mean BMD
      (RMSE = 1.103 +/- 0.262,, p<0.005). Our results indicate that the biomechanical
      strength prediction can be significantly improved in proximal femur specimens on
      MDCT images by using high-dimensional geometric features derived from SIM with
      support vector regression.

PMID- 29170580
TI  - Introducing Anisotropic Minkowski Functionals and Quantitative Anisotropy
      Measures for Local Structure Analysis in Biomedical Imaging.
AB  - The ability of Minkowski Functionals to characterize local structure in different
      biological tissue types has been demonstrated in a variety of medical image
      processing tasks. We introduce anisotropic Minkowski Functionals (AMFs) as a
      novel variant that captures the inherent anisotropy of the underlying gray-level
      structures. To quantify the anisotropy characterized by our approach, we further
      introduce a method to compute a quantitative measure motivated by a technique
      utilized in MR diffusion tensor imaging, namely fractional anisotropy. We
      showcase the applicability of our method in the research context of
      characterizing the local structure properties of trabecular bone micro
      architecture in the proximal femur as visualized on multi-detector CT. To this
      end, AMFs were computed locally for each pixel of ROIs extracted from the head,
      neck and trochanter regions. Fractional anisotropy was then used to quantify the
      local anisotropy of the trabecular structures found in these ROIs and to compare
      its distribution in different anatomical regions. Our results suggest a
      significantly greater concentration of anisotropic trabecular structures in the
      head and neck regions when compared to the trochanter region (p < 10-4 ). We also
      evaluated the ability of such AMFs to predict bone strength in the femoral head
      of proximal femur specimens obtained from 50 donors. Our results suggest that
      such AMFs, when used in conjunction with multi-regression models, can outperform
      more conventional features such as BMD in predicting failure load. We conclude
      that such anisotropic Minkowski Functionals can capture valuable information
      regarding directional attributes of local structure, which may be useful in a
      wide scope of biomedical imaging applications.

PMID- 29170581
TI  - Using Anisotropic 3D Minkowski Functionals for Trabecular Bone Characterization
      and Biomechanical Strength Prediction in Proximal Femur Specimens.
AB  - The ability of Anisotropic Minkowski Functionals (AMFs) to capture local
      anisotropy while evaluating topological properties of the underlying gray-level
      structures has been previously demonstrated. We evaluate the ability of this
      approach to characterize local structure properties of trabecular bone micro
      architecture in ex vivo proximal femur specimens, as visualized on multi-detector
      CT, for purposes of biomechanical bone strength prediction. To this end,
      volumetric AMFs were computed locally for each voxel of volumes of interest (VOI)
      extracted from the femoral head of 146 specimens. The local anisotropy captured
      by such AMFs was quantified using a fractional anisotropy measure; the magnitude
      and direction of anisotropy at every pixel was stored in histograms that served
      as a feature vectors that characterized the VOIs. A linear multi-regression
      analysis algorithm was used to predict the failure load (FL) from the feature
      sets; the predicted FL was compared to the true FL determined through
      biomechanical testing. The prediction performance was measured by the root mean
      square error (RMSE) for each feature set. The best prediction performance was
      obtained from the fractional anisotropy histogram of AMF Euler Characteristic
      (RMSE = 1.01 +/- 0.13), which was significantly better than MDCT-derived mean BMD
      (RMSE = 1.12 +/- 0.16, p<0.05). We conclude that such anisotropic Minkowski
      Functionals can capture valuable information regarding regional trabecular bone
      quality and contribute to improved bone strength prediction, which is important
      for improving the clinical assessment of osteoporotic fracture risk.

PMID- 29170582
TI  - Predicting the Biomechanical Strength of Proximal Femur Specimens with Minkowski
      Functionals and Support Vector Regression.
AB  - Regional trabecular bone quality estimation for purposes of femoral bone strength
      prediction is important for improving the clinical assessment of osteoporotic
      fracture risk. In this study, we explore the ability of 3D Minkowski Functionals
      derived from multi-detector computed tomography (MDCT) images of proximal femur
      specimens in predicting their corresponding biomechanical strength. MDCT scans
      were acquired for 50 proximal femur specimens harvested from human cadavers. An
      automated volume of interest (VOI)-fitting algorithm was used to define a
      consistent volume in the femoral head of each specimen. In these VOIs, the
      trabecular bone micro-architecture was characterized by statistical moments of
      its BMD distribution and by topological features derived from Minkowski
      Functionals. A linear multi-regression analysis and a support vector regression
      (SVR) algorithm with a linear kernel were used to predict the failure load (FL)
      from the feature sets; the predicted FL was compared to the true FL determined
      through biomechanical testing. The prediction performance was measured by the
      root mean square error (RMSE) for each feature set. The best prediction result
      was obtained from the Minkowski Functional surface used in combination with SVR,
      which had the lowest prediction error (RMSE = 0.939 +/- 0.345) and which was
      significantly lower than mean BMD (RMSE = 1.075 +/- 0.279, p<0.005). Our results
      indicate that the biomechanical strength prediction can be significantly improved
      in proximal femur specimens with Minkowski Functionals extracted from on MDCT
      images used in conjunction with support vector regression.

PMID- 29170583
TI  - Investigating the use of texture features for analysis of breast lesions on
      contrast-enhanced cone beam CT.
AB  - Cone beam computed tomography (CBCT) has found use in mammography for imaging the
      entire breast with sufficient spatial resolution at a radiation dose within the
      range of that of conventional mammography. Recently, enhancement of lesion tissue
      through the use of contrast agents has been proposed for cone beam CT. This study
      investigates whether the use of such contrast agents improves the ability of
      texture features to differentiate lesion texture from healthy tissue on CBCT in
      an automated manner. For this purpose, 9 lesions were annotated by an experienced
      radiologist on both regular and contrast-enhanced CBCT images using two
      dimensional (2D) square ROIs. These lesions were then segmented, and each pixel
      within the lesion ROI was assigned a label - lesion or non-lesion, based on the
      segmentation mask. On both sets of CBCT images, four three-dimensional (3D)
      Minkowski Functionals were used to characterize the local topology at each pixel.
      The resulting feature vectors were then used in a machine learning task involving
      support vector regression with a linear kernel (SVRlin) to classify each pixel as
      belonging to the lesion or non-lesion region of the ROI. Classification
      performance was assessed using the area under the receiver-operating
      characteristic (ROC) curve (AUC). Minkowski Functionals derived from contrast
      enhanced CBCT images were found to exhibit significantly better performance at
      distinguishing between lesion and non-lesion areas within the ROI when compared
      to those extracted from CBCT images without contrast enhancement (p < 0.05).
      Thus, contrast enhancement in CBCT can improve the ability of texture features to
      distinguish lesions from surrounding healthy tissue.

PMID- 29170584
TI  - Pair-wise Clustering of Large Scale Granger Causality Index Matrices for
      Revealing Communities.
AB  - The analysis of large ensembles of time series is a fundamental challenge in
      different domains of biomedical image processing applications, specifically in
      the area of functional MRI data processing. An important aspect of such analysis
      is the ability to reconstruct community network structures based on interactive
      behavior between different nodes of the network which are captured in such time
      series. In this study, we start with a previously proposed novel approach that
      applies the linear Granger Causality concept to very high-dimensional time
      series. This approach is based on integrating dimensionality reduction into a
      multivariate time series model. If residuals of dimensionality reduced models can
      be transformed back into the original space, prediction errors in the high
      dimensional space may be computed, and a large scale Granger Causality Index
      (lsGCI) is properly defined. The primary goal of this study was then to present
      an approach for recovering network structure from such lsGCI interactions through
      the application of pair-wise clustering. We specifically focus on a clustering
      approach based on topographic mapping of proximity data (TMP) for this purpose.
      We demonstrate our approach with a simulated network composed of five pair-wise
      different internal networks with varying strengths of community structure (based
      on the number of inter-network vertices). Our results suggest that such pair-wise
      clustering with TMP is capable of reconstructing the structure of the original
      network from lsGCI matrices that record the interactions between different nodes
      of the network when there is sufficient disparity between the intra- and inter
      network vertices.

PMID- 29170585
TI  - Large-Scale Granger Causality Analysis on Resting-State Functional MRI.
AB  - We demonstrate an approach to measure the information flow between each pair of
      time series in resting-state functional MRI (fMRI) data of the human brain and
      subsequently recover its underlying network structure. By integrating
      dimensionality reduction into predictive time series modeling, large-scale
      Granger Causality (lsGC) analysis method can reveal directed information flow
      suggestive of causal influence at an individual voxel level, unlike other
      multivariate approaches. This method quantifies the influence each voxel time
      series has on every other voxel time series in a multivariate sense and hence
      contains information about the underlying dynamics of the whole system, which can
      be used to reveal functionally connected networks within the brain. To identify
      such networks, we perform non-metric network clustering, such as accomplished by
      the Louvain method. We demonstrate the effectiveness of our approach to recover
      the motor and visual cortex from resting state human brain fMRI data and compare
      it with the network recovered from a visuomotor stimulation experiment, where the
      similarity is measured by the Dice Coefficient (DC). The best DC obtained was
      0.59 implying a strong agreement between the two networks. In addition, we
      thoroughly study the effect of dimensionality reduction in lsGC analysis on
      network recovery. We conclude that our approach is capable of detecting causal
      influence between time series in a multivariate sense, which can be used to
      segment functionally connected networks in the resting-state fMRI.

PMID- 29170586
TI  - Investigating Changes in Brain Network Properties in HIV-Associated
      Neurocognitive Disease (HAND) using Mutual Connectivity Analysis (MCA).
AB  - About 50% of subjects infected with HIV present deficits in cognitive domains,
      which are known collectively as HIV associated neurocognitive disorder (HAND).
      The underlying synaptodendritic damage can be captured using resting state
      functional MRI, as has been demonstrated by a few earlier studies. Such damage
      may induce topological changes of brain connectivity networks. We test this
      hypothesis by capturing the functional interdependence of 90 brain network nodes
      using a Mutual Connectivity Analysis (MCA) framework with non-linear time series
      modeling based on Generalized Radial Basis function (GRBF) neural networks. The
      network nodes are selected based on the regions defined in the Automated Anatomic
      Labeling (AAL) atlas. Each node is represented by the average time series of the
      voxels of that region. The resulting networks are then characterized using graph
      theoretic measures that quantify various network topology properties at a global
      as well as at a local level. We tested for differences in these properties in
      network graphs obtained for 10 subjects (6 male and 4 female, 5 HIV+ and 5 HIV-).
      Global network properties captured some differences between these subject
      cohorts, though significant differences were seen only with the clustering
      coefficient measure. Local network properties, such as local efficiency and the
      degree of connections, captured significant differences in regions of the frontal
      lobe, precentral and cingulate cortex amongst a few others. These results suggest
      that our method can be used to effectively capture differences occurring in brain
      network connectivity properties revealed by resting-state functional MRI in
      neurological disease states, such as HAND.

PMID- 29170587
TI  - Mutual Connectivity Analysis (MCA) Using Generalized Radial Basis Function Neural
      Networks for Nonlinear Functional Connectivity Network Recovery in Resting-State
      Functional MRI.
AB  - We investigate the applicability of a computational framework, called mutual
      connectivity analysis (MCA), for directed functional connectivity analysis in
      both synthetic and resting-state functional MRI data. This framework comprises of
      first evaluating non-linear cross-predictability between every pair of time
      series prior to recovering the underlying network structure using community
      detection algorithms. We obtain the non-linear cross-prediction score between
      time series using Generalized Radial Basis Functions (GRBF) neural networks.
      These cross-prediction scores characterize the underlying functionally connected
      networks within the resting brain, which can be extracted using non-metric
      clustering approaches, such as the Louvain method. We first test our approach on
      synthetic models with known directional influence and network structure. Our
      method is able to capture the directional relationships between time series (with
      an area under the ROC curve = 0.92 +/- 0.037) as well as the underlying network
      structure (Rand index = 0.87 +/- 0.063) with high accuracy. Furthermore, we test
      this method for network recovery on resting-state fMRI data, where results are
      compared to the motor cortex network recovered from a motor stimulation sequence,
      resulting in a strong agreement between the two (Dice coefficient = 0.45). We
      conclude that our MCA approach is effective in analyzing non-linear directed
      functional connectivity and in revealing underlying functional network structure
      in complex systems.

PMID- 29170588
TI  - The Biophysical Effects of Neolithic Island Colonization: General Dynamics and
      Sociocultural Implications.
AB  - Does anthropogenic environmental change constrain long-term sociopolitical
      outcomes? It is clear that human colonization of islands radically alters their
      biological and physical systems. Despite considerable contextual variability in
      local specificities of this alteration, I argue that these processes are to some
      extent regular, predictable, and have socio-political implications. Reviewing the
      data for post-colonization ecodynamics, I show that Neolithic colonization of
      previously insulated habitats drives biotic homogenization. I argue that we
      should expect such homogenization to promote regular types of change in
      biophysical systems, types of change that can be described in sum as
      environmentally convergent. Such convergence should have significant implications
      for human social organization over the long term, and general dynamics of this
      sort are relevant in the context of understanding remarkably similar social
      evolutionary trajectories towards wealth-inequality not only islands, but also
      more generally.

PMID- 29170589
TI  - The Past Ubiquity and Environment of the Lost Earth Buildings of Scotland.
AB  - This paper investigates the once ubiquitous vernacular earth-built structures of
      Scotland and how perceptions of such buildings were shaped and developed through
      periods of intense cultural and environmental change. We focus upon the past
      exploitation of traditional resources to construct vernacular architectures and
      on changes in the perception of the resultant buildings. Historic earth-built
      structures are today deeply hidden within the landscapes of Scotland, although
      they were once a common feature of both urban and rural settlements. Whilst the
      eighteenth and nineteenth century period of Improvement - during which many of
      these structures were destroyed, repurposed, or left to decay - has received
      extensive attention by historians, there exists no previous serious study of the
      human and environmental dimensions. Through analysis of the material aspects of
      landscape resource use and analysis of the historical perceptions of such use, we
      emphasize the national significance of this undervalued aspect of Scotland's
      built and cultural heritage, increasingly at risk of being lost completely,
      highlighting the prior ubiquity of mudwall structures.

PMID- 29170590
TI  - People, Patches, and Parasites: The Case of Trypanosomiasis in Zimbabwe.
AB  - Understanding the socio-ecology of disease requires careful attention to the role
      of patches within disease landscapes. Such patches, and the interfaces between
      different socio-epidemiological systems, we argue, have important implications
      for disease control. We conducted an interdisciplinary study over three years to
      investigate the spatial dynamics of human and animal trypanosomiasis in the
      Zambezi valley, Zimbabwe. We used a habitat niche model to identify changes in
      suitable habitat for tsetse fly vectors over time, and this is related to local
      villagers' understandings of where flies are found. Fly trapping and blood DNA
      analysis of livestock highlighted the patchy distribution of both flies and
      trypanosome parasites. Through livelihoods analysis we explored who makes use of
      what areas of the landscape and when, identifying the social groups most at risk.
      We conclude with a discussion of the practical implications, including the need
      for an integrated 'One Health' approach involving targeted approaches to both
      vector control and surveillance.

PMID- 29170591
TI  - New Technological Interventions in Conservation Conflicts: Countering Emotions
      and Contested Knowledge.
AB  - New technologies have increasingly featured in environmental conservation
      conflicts. We examined the deployment of imaging devices such as sonar equipment
      and cameras to survey the Fal estuary in Cornwall, UK. Due to heavy use of these
      waters, there have been several disputes coalescing around protected marine
      features, including the estuary's rare maerl beds. A comparison of two cases,
      scallop dredging and docks development, showed technical instruments being
      deployed to produce information about the marine environment as evidence to
      inform decision-making. The use of imaging devices stimulated political action
      and was regarded as a move away from emotion-based decision-making towards
      desired objectivity. Simultaneously, however, the process of deploying these
      devices was challenged and there was recognition that the resultant information
      could be used to construct the estuary as a politically charged space. Thus,
      rather than clarifying and resolving contentious issues, technological
      interventions generated new baselines for knowledge contestation and amplified
      ongoing battles for credibility and authority.

PMID- 29170592
TI  - Enablers and challenges to occupational therapists' research engagement: A
      qualitative study.
AB  - Introduction: To develop occupational therapy's evidence base and improve its
      clinical outcomes, occupational therapists must increase their research
      involvement. Barriers to research consumption and leadership are well documented,
      but those relating to delivering research interventions, less so. Yet,
      interventions need to be researched within practice to demonstrate their clinical
      effectiveness. This study aims to improve understanding of challenges and
      enablers experienced by occupational therapists who deliver interventions within
      research programmes. Method: Twenty-eight occupational therapists who
      participated in the Valuing Active Life in Dementia (VALID) research programme
      reported their experiences in five focus groups. Data were analysed thematically
      to identify key and subthemes. Results: Occupational therapists reported that
      overwhelming paperwork, use of videos, recruitment and introducing a new
      intervention challenged their research involvement, whereas support, protected
      time and a positive attitude enabled it. The impact of these challenges and
      enablers varied between therapists and organisations. Conclusion: Challenges and
      enablers to research involvement can be identified but must be addressed within
      individual and organisational contexts. Multifaceted collective action to
      minimise challenges and maximise enablers can facilitate clinicians' involvement
      in research. Using this approach should enable occupational therapists to
      increase their research involvement, thus demonstrating the clinical
      effectiveness of their interventions.

PMID- 29170593
TI  - The use of the nest for parental roosting and thermal consequences of the nest
      for nestlings and parents.
AB  - Abstract: At temperate latitudes, altricial birds and their nestlings need to
      handle night temperatures well below thermoneutrality during the breeding season.
      Thus, energy costs of thermoregulation might constrain nestling growth, and low
      nocturnal temperatures might require resources that parents could otherwise have
      invested into nestlings during the day. To manipulate parental work rate, we
      performed brood size manipulations in breeding marsh tits (Poecile palustris).
      Nest box temperatures were always well above ambient temperature and increased
      with increasing brood size. In line with predictions, a large majority of females
      (but no males) made use of this benign environment for roosting. Furthermore,
      females tending enlarged broods, thereby having to work harder during the day,
      reduced their body temperature at night. This might have reduced nocturnal energy
      expenditure. Our finding that a higher proportion of enlarged, as compared to
      control, females continued to use the nest box as roosting sites even after a
      simulated predation event despite increased vulnerability to predation, further
      highlighting the need for energy conservation in this group. High nest box
      attendance and reduced body temperature in brood-reduced females may indicate
      that these females prioritised self-maintenance by initiating other costly
      physiological adjustments, e.g. moult, when relieved from parental work. We
      suggest that the energy demand for defending homeothermy is an element of the
      general trade-off between current and future reproduction, i.e. between daytime
      investment in food provisioning and the potential short- and long-term costs of a
      reduction in body temperature and increased predation risk. Significance
      statement: Even during summer at temperate latitudes, breeding birds need to use
      energy to maintain stable body temperature. Parents, thus, need to enter the
      night with sufficient body reserves to cover energy requirements for
      thermoregulation. As these resources could be used for feeding nestling during
      the day, adaptations to reduce the cost of thermoregulation would be selected
      for. We performed brood size manipulations, thereby increasing the need for
      nestling provisioning in marsh tits (Parus palustris). We found that females
      typically spent the night in the thermally benign environment of the nest box
      together with their brood. Females working hard during the day continued to roost
      in the nest box during the night despite an increase in the perceived risk of
      nest predation. Furthermore, these females reduced their body temperature at
      night, thereby reducing the gradient between ambient and body temperature,
      further reducing the cost of thermoregulation.

PMID- 29170594
TI  - Laughter and the Management of Divergent Positions in Peer Review Interactions.
AB  - In this paper we focus on how participants in peer review interactions use
      laughter as a resource as they publicly report divergence of evaluative
      positions, divergence that is typical in the give and take of joint grant
      evaluation. Using the framework of conversation analysis, we examine the infusion
      of laughter and multimodal laugh-relevant practices into sequences of talk in
      meetings of grant reviewers deliberating on the evaluation and scoring of high
      level scientific grant applications. We focus on a recurrent sequence in these
      meetings, what we call the score-reporting sequence, in which the assigned
      reviewers first announce the preliminary scores they have assigned to the grant.
      We demonstrate that such sequences are routine sites for the use of laugh
      practices to navigate the initial moments in which divergence of opinion is made
      explicit. In the context of meetings convened for the purposes of peer review,
      laughter thus serves as a valuable resource for managing the socially delicate
      but institutionally required reporting of divergence and disagreement that is
      endemic to meetings where these types of evaluative tasks are a focal activity.

PMID- 29170595
TI  - Exploring Intergenerational Continuity in Gang Membership.
AB  - Little is known regarding intergenerational continuity in gang membership.
      Qualitative literature is suggestive of intergenerational parallelism yet no
      known research examines the causal mechanisms associated with this cycle, if it
      even exists. Prospective, longitudinal data from the Rochester Youth Development
      Study (RYDS) and the Rochester Intergenerational Study (RIGS) assess
      intergenerational continuity in gang membership among 371 parent-child dyads in a
      series of logistic regressions accounting for moderating influences of parent
      sex, child sex, parent-child sex combinations, and level of contact. Path
      analyses reported herein explore whether parenting behaviors mediate the
      relationship between parent and child gang membership among fathers and mothers,
      respectively. Three key findings emerge. First, intergenerational continuity in
      gang membership exists between mothers and daughters and, conditional on contact,
      between fathers and sons. Second, maltreatment mediates some of this relationship
      among father-son dyads. Third, no pathways to daughter gang membership were
      identified among mothers. In sum, this study provides evidence of
      intergenerational continuity in gang membership and further highlights the
      importance of parent sex, child sex, and level of contact in intergenerational
      research. Future research should further explore the causal pathways between
      parent and child gang membership.

PMID- 29170596
TI  - Early-onset Conduct Problems: Predictions from daring temperament and risk taking
      behavior.
AB  - Objective: Given its considerable public health significance, identifying
      predictors of early expressions of conduct problems is a priority. We examined
      the predictive validity of daring, a key dimension of temperament, and the
      Balloon Analog Risk Task (BART), a laboratory-based measure of risk taking
      behavior, with respect to two-year change in parent, teacher-, and youth self
      reported oppositional defiant disorder (ODD), conduct disorder (CD), and
      antisocial behavior. Method: At baseline, 150 ethnically diverse 6- to 10-year
      old (M=7.8, SD=1.1; 69.3% male) youth with (n=82) and without (n=68) DSM-IV ADHD
      completed the BART whereas parents rated youth temperament (i.e., daring);
      parents and teachers also independently rated youth ODD and CD symptoms.
      Approximately 2 years later, multi-informant ratings of youth ODD, CD, and
      antisocial behavior were gathered from rating scales and interviews. Results:
      Whereas risk taking on the BART was unrelated to conduct problems, individual
      differences in daring prospectively predicted multi-informant rated conduct
      problems, independent of baseline risk taking, conduct problems, and ADHD
      diagnostic status. Conclusion: Early differences in the propensity to show
      positive socio-emotional responses to risky or novel experiences uniquely
      predicted escalating conduct problems in childhood, even with control of other
      potent clinical correlates. We consider the role of temperament in the origins
      and development of significant conduct problems from childhood to adolescence,
      including possible explanatory mechanisms underlying these predictions.

PMID- 29170597
TI  - The Psychometric Properties of English and Spanish Versions of the Life
      Orientation Test-Revised in Hispanic Americans.
AB  - The Life Orientation Test-Revised (LOT-R) is a widely used measure of optimism
      and pessimism, with three positively worded and three negatively worded content
      items. This study examined the structural validity and invariance, internal
      consistency reliability, and convergent and divergent validity of the English and
      Spanish versions of the LOT-R among Hispanic Americans. A community sample of
      Hispanic Americans (N = 422) completed self-report measures, including the LOT-R,
      Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, in their
      preferred language of English or Spanish. Based on the literature, four
      structural models were tested: one-factor, oblique two-factor, orthogonal two
      factor method effects with positive specific factor, and orthogonal two-factor
      method effects with negative specific factor. Baseline support for both of the
      English and Spanish versions was not achieved for any model; in all models, the
      negatively worded items in Spanish had non-significant factor loadings.
      Therefore, the positively worded three-item optimism subscale of the LOT-R was
      examined separately and fit the data, with factor loadings equivalent across
      language-preference groups. Coefficient alphas for the optimism subscale were
      consistent across both language-preference groups (alphas = .61 [English] and .66
      [Spanish]). In contrast, the six-item total score and three-item pessimism
      subscale demonstrated extremely low or inconsistent alphas. Convergent and
      divergent validity were established for the optimism subscale in both languages.
      In sum, the optimism subscale of the LOT-R demonstrated minimally acceptable to
      good psychometric properties across English and Spanish language-preference
      groups. However, neither the total score nor the pessimism subscale showed
      adequate psychometric properties for Spanish-speaking Hispanic Americans, likely
      due to translation and cultural adaptation issues, and thus are not supported for
      use with this population.

PMID- 29170598
TI  - Experimental and Kinetic Modeling Studies on the Conversion of Sucrose to
      Levulinic Acid and 5-Hydroxymethylfurfural Using Sulfuric Acid in Water.
AB  - We here report experimental and kinetic modeling studies on the conversion of
      sucrose to levulinic acid (LA) and 5-hydroxymethylfurfural (HMF) in water using
      sulfuric acid as the catalyst. Both compounds are versatile building blocks for
      the synthesis of various biobased (bulk) chemicals. A total of 24 experiments
      were performed in a temperature window of 80-180  degrees C, a sulfuric acid
      concentration between 0.005 and 0.5 M, and an initial sucrose concentration
      between 0.05 and 0.5 M. Glucose, fructose, and HMF were detected as the
      intermediate products. The maximum LA yield was 61 mol %, obtained at 160 
      degrees C, an initial sucrose concentration of 0.05 M, and an acid concentration
      of 0.2 M. The maximum HMF yield (22 mol %) was found for an acid concentration of
      0.05 M, an initial sucrose concentration of 0.05 M, and a temperature of 140 
      degrees C. The experimental data were modeled using a number of possible reaction
      networks. The best model was obtained when using a first order approach in
      substrates (except for the reversion of glucose) and agreement between experiment
      and model was satisfactorily. The implication of the model regarding batch
      optimization is also discussed.

PMID- 29170599
TI  - Complexity and Challenges in Noncontact High Temperature Measurements in
      Microwave-Assisted Catalytic Reactors.
AB  - The complexity and challenges in noncontact temperature measurements inside
      microwave-heated catalytic reactors are presented in this paper. A custom
      designed microwave cavity has been used to focus the microwave field on the
      catalyst and enable monitoring of the temperature field in 2D. A methodology to
      study the temperature distribution in the catalytic bed by using a thermal camera
      in combination with a thermocouple for a heterogeneous catalytic reaction
      (methane dry reforming) under microwave heating has been demonstrated. The
      effects of various variables that affect the accuracy of temperature recordings
      are discussed in detail. The necessity of having at least one contact sensor,
      such as a thermocouple, or some other microwave transparent sensor, is
      recommended to keep track of the temperature changes occurring in the catalytic
      bed during the reaction under microwave heating.

PMID- 29170600
TI  - Production of Monosugars from Lignocellulosic Biomass in Molten Salt Hydrates:
      Process Design and Techno-Economic Analysis.
AB  - ZnCl2 hydrate, the main molten salt used in biomass conversion, combined with low
      concentration HCl is an excellent solvent for the dissolution and hydrolysis of
      the carbohydrates present in lignocellulosic biomass. The most recalcitrant
      carbohydrate, cellulose, is dissolved in a residence time less than 1 h under
      mild conditions without significant degradation. This technology is referred to
      as BIOeCON-solvent technology. Separation of the sugars from the solution is the
      main challenge. The earlier conclusion regarding the potential of zeolite beta
      for selective adsorption has been used as the basis of a scale-up study. The
      technology of choice is continuous chromatographic separation (e.g., simulated
      moving bed, SMB). The sugar monomers are separated from the sugar oligomers,
      allowing the production of monosugars at high yield, using water as an eluent.
      Results of a pilot plant study are presented showing a stable operation at high
      selectivity. Several process designs are discussed, and the techno-economic
      performance of the BIOeCON-solvent technology is demonstrated by comparison with
      the state-of-the-art technology of NREL (National Renewable Energy Laboratory),
      which is based on enzymatic conversion of cellulose. It is concluded that the
      BIOeCON-solvent technology is technically and economically viable and is
      competitive to the NREL process. Because the BIOeCON-solvent process is in an
      early stage of development and far from fully optimized, it has the potential to
      outperform the existing processes.

PMID- 29170601
TI  - Micromixing in a Rotor-Stator Spinning Disc Reactor.
AB  - This paper presents the micromixing times in a rotor-stator spinning disc
      reactor. Segregation indices are obtained at different rotational speeds
      performing the Villermaux-Dushman parallel-competitive reaction scheme.
      Consequently, the corresponding micromixing times are calculated using the
      engulfment model, while considering the self-engulfment effect. It was found that
      the segregation index decreases with an increasing disc speed. Furthermore, for
      the investigated operational conditions, the estimated micromixing times are in
      the range of 1.13 * 10-4 to 8.76 * 10-3 seconds, in agreement with the
      theoretical dependency on the energy dissipation rate of epsilon-0.5. In a rotor
      stator spinning disc reactor it is thus possible to further continue the
      theoretical trend of decreasing micromixing times with very high levels of energy
      dissipation rates that are unattainable in traditional types of process
      equipment.

PMID- 29170602
TI  - Theoretical Study of Ripening Mechanisms of Pd Clusters on Ceria.
AB  - We carried out density functional theory calculations to investigate the ripening
      of Pd clusters on CeO2(111). Starting from stable Pd n clusters (n = 1-21), we
      compared how these clusters can grow through Ostwald ripening and coalescence. As
      Pd atoms have mobility higher than that of Pd n clusters on the CeO2(111)
      surface, Ostwald ripening is predicted to be the dominant sintering mechanism.
      Particle coalescence is possible only for clusters with less than 5 Pd atoms.
      These ripening mechanisms are facilitated by adsorbed CO through lowering
      barriers for the cluster diffusion, detachment of a Pd atom from clusters, and
      transformation of initial planar clusters.

PMID- 29170603
TI  - Migration, Knowledge Transfer, and the Emergence of Australian Post-War Skiing:
      The Story of Charles William Anton.
AB  - Skiing underwent substantial changes during the post-war years when the sport
      turned into a multi-billion dollar industry and a leisure activity for the
      masses. Despite its global nature and popularity, skiing in academic writing has
      not gained much recognition. This paper explores the role of knowledge transfer
      during the pioneering phase of post-war skiing in Australia. It describes the
      life of Charles William Anton, an Austrian refugee from the Anschluss who
      migrated to Sydney and subsequently became one of the founding fathers of
      Australian post-war skiing. The following pages show the multi-layered nature of
      skiing as a global sport by exemplifying how ideas spread from pre-war Europe to
      post-war Australia. The paper will also provide a case study about refugee
      knowledge transfer and the 'productive process of absorption, adoption or
      rejection of knowledge' that takes place once an idea has been introduced into a
      new environment.

PMID- 29170604
TI  - Conceptual designs of conduction cooled MgB2 magnets for 1.5 and 3.0T full body
      MRI systems.
AB  - Conceptual designs of 1.5 and 3.0 T full-body magnetic resonance imaging (MRI)
      magnets using conduction cooled MgB2 superconductor are presented. The sizes,
      locations, and number of turns in the eight coil bundles are determined using
      optimization methods that minimize the amount of superconducting wire and produce
      magnetic fields with an inhomogeneity of less than 10 ppm over a 45 cm diameter
      spherical volume. MgB2 superconducting wire is assessed in terms of the
      transport, thermal, and mechanical properties for these magnet designs. Careful
      calculations of the normal zone propagation velocity and minimum quench energies
      provide support for the necessity of active quench protection instead of passive
      protection for medium temperature superconductors such as MgB2. A new 'active'
      protection scheme for medium Tc based MRI magnets is presented and simulations
      demonstrate that the magnet can be protected. Recent progress on persistent
      joints for multifilamentary MgB2 wire is presented. Finite difference
      calculations of the quench propagation and temperature rise during a quench
      conclude that active intervention is needed to reduce the temperature rise in the
      coil bundles and prevent damage to the superconductor. Comprehensive multiphysics
      and multiscale analytical and finite element analysis of the mechanical stress
      and strain in the MgB2 wire and epoxy for these designs are presented for the
      first time. From mechanical and thermal analysis of our designs we conclude there
      would be no damage to such a magnet during the manufacturing or operating stages,
      and that the magnet would survive various quench scenarios. This comprehensive
      set of magnet design considerations and analyses demonstrate the overall
      viability of 1.5 and 3.0 T MgB2 magnet designs.

PMID- 29170606
TI  - Religious Communities and Human Flourishing.
AB  - Participation in religious services is associated with numerous aspects of human
      flourishing, including happiness and life satisfaction, mental and physical
      health, meaning and purpose, character and virtue, and close social
      relationships. Evidence for the effects of religious communities on these
      flourishing outcomes now comes from rigorous longitudinal study designs with
      extensive confounding control. The associations with flourishing are much
      stronger for communal religious participation than for spiritual-religious
      identity or for private practices. While the social support is an important
      mechanism relating religion to health, this only explains a small portion of the
      associations. Numerous other mechanisms appear to be operative as well. It may be
      the confluence of the religious values and practices, reinforced by social ties
      and norms, that give religious communities their powerful effects on so many
      aspects of human flourishing.

PMID- 29170608
TI  - Sharp maximal and weighted estimates for multilinear iterated commutators of
      multilinear integrals with generalized kernels.
AB  - In this paper, the authors establish the sharp maximal estimates for the
      multilinear iterated commutators generated by [Formula: see text] functions and
      multilinear singular integral operators with generalized kernels. As
      applications, the boundedness of this kind of multilinear iterated commutators on
      the product of weighted Lebesgue spaces and the product of variable exponent
      Lebesgue spaces can be obtained, respectively.

PMID- 29170607
TI  - How outpatient substance abuse treatment unit director activities may affect
      provision of community outreach services.
AB  - Aims: Community outreach services play an important role in infectious disease
      prevention and engaging drug users not currently in treatment. However, fewer
      than half of US substance abuse treatment units provide these services and many
      have little financial incentive to do so. Unit directors generally have latitude
      about scope of services, including the level of outreach provided to the
      community. The current study examines how directors' interactions with external
      stakeholders affect substance abuse treatment units' provision of community
      outreach services. Methods: Cross-sectional logistic and Poisson regression
      analyses were conducted on a national sample of US outpatient substance abuse
      treatment units (N = 547). Results: Findings suggest that the amount of time
      directors spent with licensing and monitoring associations was associated with
      provision of a greater number of community outreach services, while time spent
      with professional and occupational associations was associated with provision of
      off-site human immunodeficiency virus and hepatitis C testing. Several other
      director attributes and organizational characteristics also emerged as
      significant. Conclusions: External stakeholders with whom substance abuse
      treatment directors interact may influence community outreach through their
      effects on treatment directors' strategic priorities. Implications for policy and
      prevention efforts are discussed.

PMID- 29170605
TI  - Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis,
      and Haemostasis.
AB  - Platelets are anucleated blood cells that participate in a wide range of
      physiological and pathological functions. Their major role is mediating
      haemostasis and thrombosis. In addition to these classic functions, platelets
      have emerged as important players in the innate immune system. In particular,
      they interact with leukocytes, secrete pro- and anti-inflammatory factors, and
      express a wide range of inflammatory receptors including Toll-like receptors
      (TLRs), for example, Toll-like receptor 4 (TLR4). TLR4, which is the most
      extensively studied TLR in nucleated cells, recognises lipopolysaccharides (LPS)
      that are compounds of the outer surface of Gram-negative bacteria. Unlike other
      TLRs, TLR4 is able to signal through both the MyD88-dependent and MyD88
      independent signalling pathways. Notably, despite both pathways culminating in
      the activation of transcription factors, TLR4 has a prominent functional impact
      on platelet activity, haemostasis, and thrombosis. In this review, we summarise
      the current knowledge on TLR4 signalling in platelets, critically discuss its
      impact on platelet function, and highlight the open questions in this area.

PMID- 29170609
TI  - New results on reachable set bounding for linear time delay systems with
      polytopic uncertainties via novel inequalities.
AB  - This work is further focused on analyzing a bound for a reachable set of linear
      uncertain systems with polytopic parameters. By means of L-K functional theory
      and novel inequalities, some new conditions which are expressed in the form of
      LMIs are derived. It should be noted that novel inequalities can improve upper
      bounds of Jensen inequalities, which yields less conservatism of systems.
      Consequently, some numerical examples demonstrate that the authors' results are
      somewhat more effective and advantageous compared with the previous results.

PMID- 29170610
TI  - Monotonicity, convexity, and inequalities for the generalized elliptic integrals.
AB  - We provide the monotonicity and convexity properties and sharp bounds for the
      generalized elliptic integrals [Formula: see text] and [Formula: see text]
      depending on a parameter [Formula: see text], which contains an earlier result in
      the particular case [Formula: see text].

PMID- 29170611
TI  - Factors Affecting Member Perceptions of Coalition Impact.
AB  - The purpose of this study was to identify attributes of community-based
      coalitions associated with member perceptions of greater impact. Based on
      Hackman's model of work group effectiveness, we hypothesized that member effort,
      knowledge and skill, and performance strategies would affect their perceptions of
      coalition impact. Findings from a lagged regression on a sample of forty-five
      youth-oriented coalitions indicated that two aspects of member effort were
      associated with subsequent perceived impact, as were performance strategies for
      both coalition governance and community interventions. There were no
      associations, however, between member knowledge and skill and perceived impact.
      These results suggest that leaders may improve perceived coalition impact by
      encouraging member participation in discussions and interventions and by
      developing effective strategies for both governance and implementation.

PMID- 29170612
TI  - Visual Analytics Tools for Sustainable Lifecycle Design: Current Status,
      Challenges, and Future Opportunities.
AB  - The rapid rise in technologies for data collection has created an unmatched
      opportunity to advance the use of data-rich tools for lifecycle decision-making.
      However, the usefulness of these technologies is limited by the ability to
      translate lifecycle data into actionable insights for human decision-makers. This
      is especially true in the case of sustainable lifecycle design (SLD), as the
      assessment of environmental impacts, and the feasibility of making corresponding
      design changes, often relies on human expertise and intuition. Supporting human
      sense-making in SLD requires the use of both data-driven and user-driven methods
      while exploring lifecycle data. A promising approach for combining the two is
      through the use of visual analytics (VA) tools. Such tools can leverage the
      ability of computer-based tools to gather, process, and summarize data along with
      the ability of human-experts to guide analyses through domain knowledge or data
      driven insight. In this paper, we review previous research that has created VA
      tools in SLD. We also highlight existing challenges and future opportunities for
      such tools in different lifecycle stages-design, manufacturing, distribution &
      supply chain, use-phase, end-of-life, as well as life cycle assessment. Our
      review shows that while the number of VA tools in SLD is relatively small,
      researchers are increasingly focusing on the subject matter. Our review also
      suggests that VA tools can address existing challenges in SLD and that
      significant future opportunities exist.

PMID- 29170613
TI  - An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their
      in vitro and in vivo study.
AB  - An optimization of the guanidylation process by verifying the efficacy of common
      guanylation reagents in order to obtain the guanidine derivatives of indolo[2,3
      b]quinoline has been performed. As a result, a high-yield procedure using N,N'-di
      Boc-N''-triflylguanidine was applied to synthesize the guanidine derivative of
      indolo[2,3-b]quinoline 1 in a gram scale for specific in vitro and in vivo
      biological research. Extensive studies on the antiproliferative activity against
      eight human tumor cell lines were completed. Compound 1 revealed the highest
      activity against A549 lung adenocarcinoma and MCF7 breast cancer cell lines.
      Thus, 1 was evaluated for the in vivo anticancer activity against 4T1 mammary
      gland carcinoma and KLN205 murine lung carcinoma in mouse models. The anticancer
      effect was observed in the KLN205 model with a 37% tumor growth inhibition at the
      20 mg/kg dose. This anticancer activity of 1 was comparable to that of
      cyclophosphamide which inhibited murine lung tumor growth in the range of 27-43%
      at the dose of 100 mg/kg. The biochemistry research after 1 admission, including
      measurements of blood parameters like alanine aminotransferase, aspartate
      aminotransferase, lactate dehydrogenase, and urea and creatinine, were also
      performed.

PMID- 29170614
TI  - Partisan Bias in Message Selection: Media Gatekeeping of Party Press Releases.
AB  - Parties try to shape media coverage in ways that are favorable to them, but what
      determines whether media outlets pick up and report on party messages? Based on
      content analyses of 1,496 party press releases and 6,512 media reports from the
      2013 Austrian parliamentary election campaign, we show that media coverage of
      individual party messages is influenced not just by news factors, but also by
      partisan bias. The media are therefore more likely to report on messages from
      parties their readers favor. Importantly, this effect is greater rather than
      weaker when these messages have high news value. These findings have important
      implications for understanding the media's role in elections and representative
      democracies in general.

PMID- 29170615
TI  - Caregivers' positive emotional expression and children's psychological
      functioning after parental loss.
AB  - The death of a loved one, particularly a parent, has been identified as not only
      the most common, but also the most distressing form of adversity youth may
      experience in their lifetime. Surviving caregivers' communication with their
      children may play a critical role in shaping bereaved children's psychological
      functioning. However, few studies have examined the specific content (e.g., word
      usage) of caregivers' verbal communication as a predictor of psychological
      functioning in bereaved youth. In a sample of 39 parentally-bereaved children and
      their surviving caregivers, we investigated whether the frequency of caregivers'
      use of positive emotion words (e.g., "love", "happy", "hope") during a
      reminiscing task about the deceased was associated with children's psychological
      functioning and coping. In a cross-sectional analysis, we specifically examined
      whether these associations were moderated by the amount of time passed since
      children lost their parents. The Linguistic Inquiry and Word Count Program (LIWC)
      was used to code and evaluate the percentage of positive emotion words caregivers
      used during the discussion. When caregivers used more positive emotion words,
      children were less likely to experience depression, anxiety, and avoidant coping.
      Those associations were present for children who had experienced parental loss at
      least 105 days prior to the study. Our findings have implications for how
      caregivers can support their children and help to alleviate psychological
      distress in the aftermath of parental loss.

PMID- 29170617
TI  - Optimal Computing Budget Allocation for Particle Swarm Optimization in Stochastic
      Optimization.
AB  - Particle Swarm Optimization (PSO) is a popular metaheuristic for deterministic
      optimization. Originated in the interpretations of the movement of individuals in
      a bird flock or fish school, PSO introduces the concept of personal best and
      global best to simulate the pattern of searching for food by flocking and
      successfully translate the natural phenomena to the optimization of complex
      functions. Many real-life applications of PSO cope with stochastic problems. To
      solve a stochastic problem using PSO, a straightforward approach is to equally
      allocate computational effort among all particles and obtain the same number of
      samples of fitness values. This is not an efficient use of computational budget
      and leaves considerable room for improvement. This paper proposes a seamless
      integration of the concept of optimal computing budget allocation (OCBA) into PSO
      to improve the computational efficiency of PSO for stochastic optimization
      problems. We derive an asymptotically optimal allocation rule to intelligently
      determine the number of samples for all particles such that the PSO algorithm can
      efficiently select the personal best and global best when there is stochastic
      estimation noise in fitness values. We also propose an easy-to-implement
      sequential procedure. Numerical tests show that our new approach can obtain much
      better results using the same amount of computational effort.

PMID- 29170618
TI  - Bi2Se3 van der Waals Virtual Substrates for II-VI Heterostructures.
AB  - We report on the growth and characterization of optical quality multiple quantum
      well structures of Zn x Cd1-x Se/Zn x Cd y Mg1-x-y Se on an ultra-thin
      Bi2Se3/CdTe virtual substrate on c-plane Al2O3 (sapphire). Excellent quality
      highly oriented films grown along the (111) direction were achieved as evidenced
      by reflection high energy electron diffraction and X-ray diffraction studies. We
      also observed room temperature and 77 K photoluminescence emission with peak
      energies at 77 K of 2.407 eV and linewidths of 56 meV comparable to those
      achieved on structures grown on InP. Exfoliation of the structures is also
      possible due to the van der Waals bonding of Bi2Se3. Exfoliated (substrate free)
      films exhibit photoluminescence emission nearly identical to that of the
      supported film. Additionally, contactless electroreflectance measurements show
      good agreement with simulations of the multiple quantum well structure as well as
      evidence of excited state levels. These results open new avenues of research for
      substrate independent epitaxy and the possibility of ultra-thin electronics.

PMID- 29170616
TI  - Considering passive mechanical properties and patient user motor performance in
      lower limb prosthesis design optimization to enhance rehabilitation outcomes.
AB  - Background: Selection of prosthesis mechanical characteristics to restore
      function of persons with lower-limb loss can be framed as an optimization problem
      to satisfy a given performance objective. However, the choice of a particular
      objective is critical, and considering only device and generalizable outcomes
      across users without accounting for inherent motor performance likely restricts a
      given patient from fully realizing the benefits of a prosthetic intervention.
      Objectives: This review presents methods for optimizing passive below-knee
      prosthesis designs to maximize rehabilitation outcomes and how considerations on
      patient motor performance may enhance these outcomes. Major Findings: Available
      literature supports that considering patient-specific variables pertaining to
      motor performance permits a multidimensional landscape relating device
      characteristics and user function, which may yield more accurate predictions of
      rehabilitation outcomes for individual patients. Moreover, the addition of
      targeted physical therapeutic interventions that encourage user self-organization
      may further improve these outcomes. We note the potential of existing paradigms
      to address these additional dimensions, and we encourage investigators to
      consider the many different performance objectives available for prosthesis
      optimization. Conclusions: By considering user motor performance in combination
      with prosthesis mechanical characteristics, a staged optimization approach can be
      formulated which acknowledges that device modifications may only improve outcomes
      to a certain extent and user self-organization is a critical component to
      complete rehabilitation. An iterative process that can be integrated within
      existing rehabilitative practices accounts for changes in patient status through
      combined targeted prosthetic solutions and physical therapeutic techniques, and
      embodies the concept of personalized intervention for patients with lower limb
      loss.

PMID- 29170619
TI  - Internal and International Mobility as Adaptation to Climatic Variability in
      Contemporary Mexico: Evidence from the Integration of Census and Satellite Data.
AB  - Migration provides a strategy for rural Mexican households to cope with, or adapt
      to, weather events and climatic variability. Yet prior studies on "environmental
      migration" in this context have not examined the differences between choices of
      internal (domestic) or international movement. In addition, much of the prior
      work relied on very coarse spatial scales to operationalize the environmental
      variables such as rainfall patterns. To overcome these limitations, we use fine
      grain rainfall estimates derived from NASA's Tropical Rainfall Measuring Mission
      (TRMM) satellite. The rainfall estimates are combined with Population and
      Agricultural Census information to examine associations between environmental
      changes and municipal rates of internal and international migration 2005-2010.
      Our findings suggest that municipal-level rainfall deficits relative to
      historical levels are an important predictor of both international and internal
      migration, especially in areas dependent on seasonal rainfall for crop
      productivity. Although our findings do not contradict results of prior studies
      using coarse spatial resolution, they offer clearer results and a more spatially
      nuanced examination of migration as related to social and environmental
      vulnerability and thus higher degrees of confidence.

PMID- 29170620
TI  - The Coordination Abilities of Three Novel Analogues of Saliva Peptides: The
      Influence of Structural Modification on the Copper Binding.
AB  - Three novel analogues of salivary peptides as sialorphin (QHNPR) and opiorphin
      (QRFSR) were synthesized by the solid-phase method. The sequences of these
      ligands were following: AHNPR, QANPR and QRFPR. The aim of our work was
      investigation in what way some structural modifications may impact on
      coordination abilities of studied peptides. In this work we presented the
      interaction of pentapeptides with copper(II) ions in wide range of pH. To
      determine the coordination model of ligands there were carried out several
      studies by spectroscopy (UV-Vis, CD) methods and potentiometric measurements.

PMID- 29170621
TI  - The Analysis of Cu(II)/Zn(II) Cyclopeptide System as Potential Cu,ZnSOD Mimic
      Center.
AB  - In this paper are presented the features of copper (II) and zinc (II)
      heteronuclear complexes of the cyclic peptide-c(HKHGPG)2. The coordination
      properties of ligand were studied by potentiometric, UV-Vis and CD spectroscopic
      methods. These experiments were carried out in aqueous solutions at 298 K
      depending on pH. It turned out that in a physiological pH dominates Cu(II)/Zn(II)
      complex ([CuZnL]4+) which could mimic the active center of superoxide dismutase
      (Cu,ZnSOD). In next step we performed in vitro research on Cu,ZnSOD activity for
      [CuZnL]4+ complex existing in 7.4 pH by the method of reduction of nitroblue
      tetrazolium (NBT). Also mono- and di-nuclear copper (II) complexes of this ligand
      were examined. The ability of inhibition free radical reaction were compared for
      all complexes. The results of these studies show that Cu(II) mono-, di-nuclear
      and Cu(II)/Zn(II) complexes becoming to new promising synthetic superoxide
      dismutase mimetics, and should be considered for further biological assays.

PMID- 29170622
TI  - Comparisons of Alcohol Consumption by Time-Line Follow Back vs. Smartphone-Based
      Daily Interviews.
AB  - This study compared alcohol consumption data collected through daily interviews
      on a smartphone with data collected via the Timeline Follow-Back (TLFB) during a
      6-week pilot study of a smartphone-based alcohol intervention system. The focus
      of the study was to assess for discrepancies between the two measurement
      methodologies on commonly utilized alcohol outcome variables. Twenty-five
      participants between 22 and 45 years of age and were drinking heavily at study
      incipience completed a 6-week alcohol intervention delivered by a smartphone
      application that monitored drinking through a daily interview. Participants also
      completed a TLFB of their alcohol consumption during the intervention period.
      Difference scores were calculated by subtracting the average weekly outcome
      variables derived from the smartphone daily interview from the average weekly
      outcome variables derived from the TLFB which yielded six discrepancy scores for
      each of the 25 participants and resulted in 150 observations. Heirarchical linear
      modeling indicated that the TLFB and smartphone daily interview methods did not
      produce significant discrepancies over the 6-week interval when examining percent
      of heavy drinking days and percent of days abstinent. However, discrepancies on
      drinks per drinking day increased substantially over time, suggesting that it is
      susceptible to recall bias when assessed by the TLFB. Results also indicated that
      participants under-reported their drinking on the TLFB compared to the daily
      smartphone-based assessment. Results indicate that outside of assessing for
      extreme drinking (binge or no drinking), the TLFB should be used cautiously and
      that smartphone apps represent a promising method for accurately assessing
      alcohol consumption over time.

PMID- 29170623
TI  - N2O strongly prevents adhesion formation and postoperative pain in open surgery
      through a drug-like effect.
AB  - Background: Microsurgical tenets and peritoneal conditioning during laparoscopic
      surgery (LS) decrease postoperative adhesions and pain. For a trial in human, the
      strong beneficial effects of N2O needed to be confirmed in open surgery (OS).
      Results: In a mouse model for OS, the effect of the gas environment upon
      adhesions was evaluated. Experiment I evaluated desiccation and the duration of
      exposure to CO2, N2O or CO2 + 4%O2. Experiment II evaluated the dose-response
      curve of adding N2O to CO2. Experiment III compared humidified CO2 + 10% N2O
      during LS and OS.In OS, 30- and 60-min exposure to non-humidified CO2 caused
      mortality of 33 and 100%, respectively. Mortality was prevented by
      humidification, by dry N2O or dry CO2 + 4%O2. Adhesions increased with the
      duration of exposure to CO2 (p < 0.0001) and decreased slightly by humidification
      or by the addition of 4% O2. N2O strongly decreased adhesions at concentrations
      of 5% or greater. With humidified CO2 + 10% N2O, adhesion formation was similar
      in OS and LS. Conclusions: The drug-like and strong beneficial effect of low
      concentrations of N2O is confirmed in OS.

PMID- 29170624
TI  - Estimating Memory Deterioration Rates Following Neurodegeneration and Traumatic
      Brain Injuries in a Hopfield Network Model.
AB  - Neurodegenerative diseases and traumatic brain injuries (TBI) are among the main
      causes of cognitive dysfunction in humans. At a neuronal network level, they both
      extensively exhibit focal axonal swellings (FAS), which in turn, compromise the
      information encoded in spike trains and lead to potentially severe functional
      deficits. There are currently no satisfactory quantitative predictors of decline
      in memory-encoding neuronal networks based on the impact and statistics of FAS.
      Some of the challenges of this translational approach include our inability to
      access small scale injuries with non-invasive methods, the overall complexity of
      neuronal pathologies, and our limited knowledge of how networks process
      biological signals. The purpose of this computational study is three-fold: (i) to
      extend Hopfield's model for associative memory to account for the effects of FAS,
      (ii) to calibrate FAS parameters from biophysical observations of their
      statistical distribution and size, and (iii) to systematically evaluate
      deterioration rates for different memory-recall tasks as a function of FAS
      injury. We calculate deterioration rates for a face-recognition task to account
      for highly correlated memories and also for a discrimination task of random,
      uncorrelated memories with a size at the capacity limit of the Hopfield network.
      While it is expected that the performance of any injured network should decrease
      with injury, our results link, for the first time, the memory recall ability to
      observed FAS statistics. This allows for plausible estimates of cognitive decline
      for different stages of brain disorders within neuronal networks, bridging
      experimental observations following neurodegeneration and TBI with compromised
      memory recall. The work lends new insights to help close the gap between theory
      and experiment on how biological signals are processed in damaged, high
      dimensional functional networks, and towards positing new diagnostic tools to
      measure cognitive deficits.

PMID- 29170625
TI  - Connectopathy in Autism Spectrum Disorders: A Review of Evidence from Visual
      Evoked Potentials and Diffusion Magnetic Resonance Imaging.
AB  - Individuals with autism spectrum disorder (ASD) show superior performance in
      processing fine details; however, they often exhibit impairments of gestalt face,
      global motion perception, and visual attention as well as core social deficits.
      Increasing evidence has suggested that social deficits in ASD arise from abnormal
      functional and structural connectivities between and within distributed cortical
      networks that are recruited during social information processing. Because the
      human visual system is characterized by a set of parallel, hierarchical,
      multistage network systems, we hypothesized that the altered connectivity of
      visual networks contributes to social cognition impairment in ASD. In the present
      review, we focused on studies of altered connectivity of visual and attention
      networks in ASD using visual evoked potentials (VEPs), event-related potentials
      (ERPs), and diffusion tensor imaging (DTI). A series of VEP, ERP, and DTI studies
      conducted in our laboratory have demonstrated complex alterations (impairment and
      enhancement) of visual and attention networks in ASD. Recent data have suggested
      that the atypical visual perception observed in ASD is caused by altered
      connectivity within parallel visual pathways and attention networks, thereby
      contributing to the impaired social communication observed in ASD. Therefore, we
      conclude that the underlying pathophysiological mechanism of ASD constitutes a
      "connectopathy."

PMID- 29170626
TI  - Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in
      Primary Sensory Neurons.
AB  - Peripheral nerve injury increased the expression of the DNA methyltransferase 3A
      (Dnmt3a) mRNA and its encoding Dnmt3a protein in injured dorsal root ganglia
      (DRG). This increase is considered as an endogenous instigator in neuropathic
      pain genesis through epigenetic silencing of pain-associated genes (such as
      Oprm1) in injured DRG. However, how DRG DNMT3a is increased following peripheral
      nerve injury is still elusive. We reported here that peripheral nerve injury
      caused by the fifth spinal nerve ligation (SNL) downregulated microRNA (miR)-143
      expression in injured DRG. This downregulation was required for SNL-induced DRG
      Dnmt3a increase as rescuing miR-143 downregulation through microinjection of miR
      143 mimics into injured DRG blocked the SNL-induced increase in Dnmt3a and
      restored the SNL-induced decreases in Oprm1 mRNA and its encoding mu opioid
      receptor (MOR) in injured DRG, impaired spinal cord central sensitization and
      neuropathic pain, and improved morphine analgesic effects following SNL.
      Mimicking SNL-induced DRG miR-143 downregulation through DRG microinjection of
      miR143 inhibitors in naive rats increased the expression of Dnmt3a and reduced
      the expression of Oprm1 mRNA and MOR in injected DRG and produced neuropathic
      pain-like symptoms. These findings suggest that miR-143 is a negative regulator
      in Dnmt3a expression in the DRG under neuropathic pain conditions and may be a
      potential target for therapeutic management of neuropathic pain.

PMID- 29170627
TI  - Combinatorial In Silico Strategy towards Identifying Potential Hotspots during
      Inhibition of Structurally Identical HDAC1 and HDAC2 Enzymes for Effective
      Chemotherapy against Neurological Disorders.
AB  - Histone deacetylases (HDACs) regulate epigenetic gene expression programs by
      modulating chromatin architecture and are required for neuronal development.
      Dysregulation of HDACs and aberrant chromatin acetylation homeostasis have been
      implicated in various diseases ranging from cancer to neurodegenerative
      disorders. Histone deacetylase inhibitors (HDACi), the small molecules
      interfering HDACs have shown enhanced acetylation of the genome and are gaining
      great attention as potent drugs for treating cancer and neurodegeneration. HDAC2
      overexpression has implications in decreasing dendrite spine density, synaptic
      plasticity and in triggering neurodegenerative signaling. Pharmacological
      intervention against HDAC2 though promising also targets neuroprotective HDAC1
      due to high sequence identity (94%) with former in catalytic domain, culminating
      in debilitating off-target effects and creating hindrance in the defined
      intervention. This emphasizes the need of designing HDAC2-selective inhibitors to
      overcome these vicious effects and for escalating the therapeutic efficacy. Here
      we report a top-down combinatorial in silico approach for identifying the
      structural variants that are substantial for interactions against HDAC1 and HDAC2
      enzymes. We used extra-precision (XP)-molecular docking, Molecular Mechanics
      Generalized Born Surface Area (MMGBSA) for predicting affinity of inhibitors
      against the HDAC1 and HDAC2 enzymes. Importantly, we employed a novel in silico
      strategy of coupling the state-of-the-art molecular dynamics simulation (MDS) to
      energetically-optimized structure based pharmacophores (e-Pharmacophores) method
      via MDS trajectory clustering for hypothesizing the e-Pharmacophore models.
      Further, we performed e-Pharmacophores based virtual screening against phase
      database containing millions of compounds. We validated the data by performing
      the molecular docking and MM-GBSA studies for the selected hits among the
      retrieved ones. Our studies attributed inhibitor potency to the ability of
      forming multiple interactions and infirm potency to least interactions. Moreover,
      our studies delineated that a single HDAC inhibitor portrays differential
      features against HDAC1 and HDAC2 enzymes. The high affinity and selective HDAC2
      inhibitors retrieved through e-Pharmacophores based virtual screening will play a
      critical role in ameliorating neurodegenerative signaling without hampering the
      neuroprotective isoform (HDAC1).

PMID- 29170628
TI  - Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic
      Variants with Synergistic Effect on Clinical Phenotype.
AB  - Amyotrophic lateral sclerosis (ALS) is underpinned by an oligogenic rare variant
      architecture. Identified genetic variants of ALS include RNA-binding proteins
      containing prion-like domains (PrLDs). We hypothesized that screening genes
      encoding additional similar proteins will yield novel genetic causes of ALS. The
      most common genetic variant of ALS patients is a G4C2-repeat expansion within
      C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A
      logical consequence of this is that loss-of-function mutations in G4C2-binding
      partners might contribute to ALS pathogenesis independently of and/or
      synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA
      encoding either RNA-binding proteins or known ALS genes (n = 274 genes) was
      performed in ALS patients to identify rare deleterious genetic variants and
      explore genotype-phenotype relationships. Genomic DNA was extracted from 103 ALS
      patients including 42 familial ALS patients and 61 young-onset (average age of
      onset 41 years) sporadic ALS patients; patients were chosen to maximize the
      probability of identifying genetic causes of ALS. Thirteen patients carried a
      G4C2-repeat expansion of C9ORF72. We identified 42 patients with rare deleterious
      variants; 6 patients carried more than one variant. Twelve mutations were
      discovered in known ALS genes which served as a validation of our strategy. Rare
      deleterious variants in RNA-binding proteins were significantly enriched in ALS
      patients compared to control frequencies (p = 5.31E-18). Nineteen patients
      featured at least one variant in a RNA-binding protein containing a PrLD. The
      number of variants per patient correlated with rate of disease progression (t
      test, p = 0.033). We identified eighteen patients with a single variant in a G4C2
      repeat binding protein. Patients with a G4C2-binding protein variant in
      combination with a C9ORF72 expansion had a significantly faster disease course (t
      test, p = 0.025). Our data are consistent with an oligogenic model of ALS. We
      provide evidence for a number of entirely novel genetic variants of ALS caused by
      mutations in RNA-binding proteins. Moreover we show that these mutations act
      synergistically with each other and with C9ORF72 expansions to modify the
      clinical phenotype of ALS. A key finding is that this synergy is present only
      between functionally interacting variants. This work has significant implications
      for ALS therapy development.

PMID- 29170629
TI  - Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain
      Overgrowth by Expansion of the Neural Progenitor Pool.
AB  - Hydrocephalus can occur in children alone or in combination with other
      neurodevelopmental disorders that are often associated with brain overgrowth.
      Despite the severity of these disorders, the molecular and cellular mechanisms
      underlying these pathologies and their comorbidity are poorly understood. Here,
      we studied the consequences of genetically inactivating in mice dual-specificity
      phosphatase 16 (Dusp16), which is known to negatively regulate mitogen-activated
      protein kinases (MAPKs) and which has never previously been implicated in brain
      development and disorders. Mouse mutants lacking a functional Dusp16 gene (Dusp16
      /-) developed fully-penetrant congenital obstructive hydrocephalus together with
      brain overgrowth. The midbrain aqueduct in Dusp16-/- mutants was obstructed
      during mid-gestation by an expansion of neural progenitors, and during later
      gestational stages by neurons resulting in a blockage of cerebrospinal fluid
      (CSF) outflow. In contrast, the roof plate and ependymal cells developed
      normally. We identified a delayed cell cycle exit of neural progenitors in Dusp16
      /- mutants as a cause of progenitor overproliferation during mid-gestation. At
      later gestational stages, this expanded neural progenitor pool generated an
      increased number of neurons associated with enlarged brain volume. Taken
      together, we found that Dusp16 plays a critical role in neurogenesis by balancing
      neural progenitor cell proliferation and neural differentiation. Moreover our
      results suggest that a lack of functional Dusp16 could play a central role in the
      molecular mechanisms linking brain overgrowth and hydrocephalus.

PMID- 29170630
TI  - Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of
      Rodent Visual Cortex.
AB  - The microdomain that orchestrates action potential initiation in neurons is the
      axon initial segment (AIS). It has long been considered to be a rather
      homogeneous domain at the very proximal axon hillock with relatively stable
      length, particularly in cortical pyramidal cells. However, studies in other brain
      regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge
      from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal
      neurons in rat somatosensory cortex, axons have a dendritic origin. Consequently,
      the AIS is separated from the soma. Recent in vitro and in vivo studies have
      shown that cellular excitability is a function of AIS length/position and
      somatodendritic morphology, undermining a potentially significant impact of AIS
      heterogeneity for neuronal function. We therefore investigated neocortical axon
      morphology and AIS composition, hypothesizing that the initial observation of
      seemingly homogeneous AIS is inadequate and needs to take into account neuronal
      cell types. Here, we biolistically transfected cortical neurons in organotypic
      cultures to visualize the entire neuron and classify cell types in combination
      with immunolabeling against AIS markers. Using confocal microscopy and
      morphometric analysis, we investigated axon origin, AIS position, length,
      diameter as well as distance to the soma. We find a substantial AIS heterogeneity
      in visual cortical neurons, classified into three groups: (I) axons with somatic
      origin with proximal AIS at the axon hillock; (II) axons with somatic origin with
      distal AIS, with a discernible gap between the AIS and the soma; and (III) axons
      with dendritic origin (axon-carrying dendrite cell, AcD cell) and an AIS either
      starting directly at the axon origin or more distal to that point. Pyramidal
      cells have significantly longer AIS than interneurons. Interneurons with vertical
      columnar axonal projections have significantly more distal AIS locations than all
      other cells with their prevailing phenotype as an AcD cell. In contrast, neurons
      with perisomatic terminations display most often an axon originating from the
      soma. Our data contribute to the emerging understanding that AIS morphology is
      highly variable, and potentially a function of the cell type.

PMID- 29170631
TI  - Histamine H3 Heteroreceptors Suppress Glutamatergic and GABAergic Synaptic
      Transmission in the Rat Insular Cortex.
AB  - Histamine H3 receptors are autoreceptors that regulate histamine release from
      histaminergic neuronal terminals. The cerebral cortex, including the insular
      cortex (IC), expresses abundant H3 receptors; however, the functions and
      mechanisms of H3 receptors remain unknown. The aim of this study was to elucidate
      the functional roles of H3 in synaptic transmission in layer V of the rat IC.
      Unitary excitatory and inhibitory postsynaptic currents (uEPSCs and uIPSCs) were
      obtained through paired whole-cell patch-clamp recording in cerebrocortical slice
      preparations. The H3 receptor agonist, R-alpha-methylhistamine (RAMH), reduced
      the uEPSC amplitude obtained from pyramidal cell to pyramidal cell or GABAergic
      interneuron connections. Similarly, RAMH reduced the uIPSC amplitude in GABAergic
      interneuron to pyramidal cell connections. RAMH-induced decreases in both the
      uEPSC and uIPSC amplitudes were accompanied by increases in the failure rate and
      paired-pulse ratio. JNJ 5207852 dihydrochloride or thioperamide, H3 receptor
      antagonists, inhibited RAMH-induced suppression of uEPSCs and uIPSCs.
      Unexpectedly, thioperamide alone increased the uIPSC amplitude, suggesting that
      thioperamide was likely to act as an inverse agonist. Miniature EPSC or IPSC
      recordings support the hypothesis that the activation of H3 receptors suppresses
      the release of glutamate and GABA from presynaptic terminals. The colocalization
      of H3 receptors and glutamate decarboxylase or vesicular glutamate transport
      protein 1 in presynaptic axon terminals was confirmed through double pre
      embedding microscopy, using a combination of pre-embedding immunogold and
      immunoperoxidase techniques. The suppressive regulation of H3 heteroreceptors on
      synaptic transmission might mediate the regulation of sensory information
      processes, such as gustation and visceral sensation, in the IC.

PMID- 29170633
TI  - Editorial: The Clinical and Ethical Practice of Neuromodulation - Deep Brain
      Stimulation and Beyond.

PMID- 29170632
TI  - Transcriptional and Post-Transcriptional Mechanisms of the Development of
      Neocortical Lamination.
AB  - The neocortex is a laminated brain structure that is the seat of higher cognitive
      capacity and responses, long-term memory, sensory and emotional functions, and
      voluntary motor behavior. Proper lamination requires that progenitor cells give
      rise to a neuron, that the immature neuron can migrate away from its mother cell
      and past other cells, and finally that the immature neuron can take its place and
      adopt a mature identity characterized by connectivity and gene expression; thus
      lamination proceeds through three steps: genesis, migration, and maturation. Each
      neocortical layer contains pyramidal neurons that share specific morphological
      and molecular characteristics that stem from their prenatal birth date.
      Transcription factors are dynamic proteins because of the cohort of downstream
      factors that they regulate. RNA-binding proteins are no less dynamic, and play
      important roles in every step of mRNA processing. Indeed, recent screens have
      uncovered post-transcriptional mechanisms as being integral regulatory mechanisms
      to neocortical development. Here, we summarize major aspects of neocortical
      laminar development, emphasizing transcriptional and post-transcriptional
      mechanisms, with the aim of spurring increased understanding and study of its
      intricacies.

PMID- 29170634
TI  - Lost in Time and Space: States of High Arousal Disrupt Implicit Acquisition of
      Spatial and Sequential Context Information.
AB  - Biased cognition during high arousal states is a relevant phenomenon in a variety
      of topics: from the development of post-traumatic stress disorders or stress
      triggered addictive behaviors to forensic considerations regarding crimes of
      passion. Recent evidence indicates that arousal modulates the engagement of a
      hippocampus-based "cognitive" system in favor of a striatum-based "habit" system
      in learning and memory, promoting a switch from flexible, contextualized to more
      rigid, reflexive responses. Existing findings appear inconsistent, therefore it
      is unclear whether and which type of context processing is disrupted by enhanced
      arousal. In this behavioral study, we investigated such arousal-triggered
      cognitive-state shifts in human subjects. We validated an arousal induction
      procedure (three experimental conditions: violent scene, erotic scene, neutral
      control scene) using pupillometry (Preliminary Experiment, n = 13) and randomly
      administered this method to healthy young adults to examine whether high arousal
      states affect performance in two core domains of contextual processing, the
      acquisition of spatial (spatial discrimination paradigm; Experiment 1, n = 66)
      and sequence information (learned irrelevance paradigm; Experiment 2, n = 84). In
      both paradigms, spatial location and sequences were encoded incidentally and both
      displacements when retrieving spatial position as well as the predictability of
      the target by a cue in sequence learning changed stepwise. Results showed that
      both implicit spatial and sequence learning were disrupted during high arousal
      states, regardless of valence. Compared to the control group, participants in the
      arousal conditions showed impaired discrimination of spatial positions and
      abolished learning of associative sequences. Furthermore, Bayesian analyses
      revealed evidence against the null models. In line with recent models of stress
      effects on cognition, both experiments provide evidence for decreased engagement
      of flexible, cognitive systems supporting encoding of context information in
      active cognition during acute arousal, promoting reduced sensitivity for
      contextual details. We argue that arousal fosters cognitive adaptation towards
      less demanding, more present-oriented information processing, which prioritizes a
      current behavioral response set at the cost of contextual cues. This transient
      state of behavioral perseverance might reduce reliance on context information in
      unpredictable environments and thus represent an adaptive response in certain
      situations.

PMID- 29170635
TI  - Interactions of Insula Subdivisions-Based Networks with Default-Mode and Central
      Executive Networks in Mild Cognitive Impairment.
AB  - Interactions between the brain networks and subnetworks are crucial for active
      and resting cognitive states. Whether a subnetwork can restore the adequate
      function of the parent network whenever a disease state affects the parent
      network is unclear. Investigations suggest that the control of the anterior
      insula-based network (AIN) over the default-mode network (DMN) and central
      executive network (CEN) is decreased in individuals with mild cognitive
      impairment (MCI). Here, we hypothesized that the posterior insula-based network
      (PIN) attempts to compensate for this decrease. To test this, we compared a group
      of MCI and normal cognitive individuals. A dynamical causal modeling method has
      been employed to investigate the dynamic network controls/modulations. We used
      the resting state functional MRI data, and assessed the interactions of the AIN
      and of the PIN, respectively, over the DMN and CEN. We found that the greater
      control of AIN than that of DMN (Wilcoxon rank sum: Z = 1.987; p = 0.047) and CEN
      (Z = 3.076; p = 0.002) in normal group and the lower (impaired) control of AIN
      than that of CEN (Z = 8.602; p = 7.816 * 10-18). We further revealed that the PIN
      control was significantly higher than that of DMN (Z = 6.608; p = 3.888 * 10-11)
      and CEN (Z = 6.429; p = 1.278 * 10-10) in MCI group where the AIN was impaired,
      but that control was significantly lower than of DMN (Z = 5.285; p = 1.254 * 10
      7) and CEN (Z = 5.404; p = 6.513 * 10-8) in normal group. Finally, the global
      cognitive test score assessed using Montreal cognitive assessment and the network
      modulations were correlated (Spearman's correlation: r = 0.47; p = 3.76 * 10-5
      and r = -0.43; p = 1.97 * 10-4). These findings might suggest the flexible
      functional profiles of AIN and PIN in normal aging and MCI.

PMID- 29170637
TI  - Effect of Standardized Warfarin Treatment Protocol on Anticoagulant Effect:
      Comparison of a Warfarin Medication Therapy Adherence Clinic with Usual Medical
      Care.
AB  - : Objective: To evaluate the impact of pharmacist-led warfarin management and
      standardized treatment protocol. Methods: A retrospective cohort study was
      carried out in a cardiology referral hospital located in central Kuala Lumpur,
      Malaysia, from 2009 to 2014. The inclusion criteria were: adult patients who were
      diagnosed and treated for atrial fibrillation (AF) with warfarin, attended the
      warfarin medication therapy adherence clinic (WMTAC) for at least 12 weeks, and
      with at least four international normalized ratio (INR) readings. The electronic
      medical records were reviewed for demographics, type of AF, warfarin dose, INRs,
      adverse events, co-morbidities, and drug-drug interactions. The outcome measures
      included the mean time to therapeutic INR, the mean percentage of time in
      therapeutic range (TTR), bleeding events, and common drug interactions. Results:
      Out of 473 patients, 151 patients fulfilled the inclusion criteria. The findings
      revealed that there were significant associations between the usual medical care
      (UMC) group and pharmacist-led WMTAC in terms of TTR (p = 0.01) and INR (p =
      0.02) levels. A positive impact of pharmacists' involvement in the WMTAC clinic
      was where the "pharmacist's recommendation accepted" (p = 0.01) and "expanded
      therapeutic INR range" (p = 0.04) were statistically significantly higher in the
      WMTAC group. Conclusion: There was a significant positive association between the
      pharmacist-led WMTAC and anticoagulation effect (therapeutic TTR, INR). The
      identified findings revealed that expanded role of pharmacist in pharmacist
      managed warfarin therapy is beneficial to optimize the warfarin therapy. This
      study also highlighted the critical roles that pharmacists can actively play to
      ensure optimal anticoagulation pharmaceutical care. Key messages: What is already
      known on this subject?* Pharmacist-managed warfarin therapy is beneficial for
      optimizing warfarin therapy. In such therapy, recommendations such as dose
      adjustment and safer alternative drugs (given drug-drug interactions and/or food
      drug interactions) are made.* The active involvement of pharmacists in warfarin
      adherence clinics could significantly improve adherence.* However, the warfarin
      treatment outcomes from UMC, pharmacist-and-physician-led care and pharmacist-led
      care have not been studied.* The impact of the implementation of the standardized
      protocol for the warfarin adherence clinic has not been assessed.What this study
      adds?* INR levels among UMC group and WMTAC group were significantly different.*
      Though the TTR level for the WMTAC group was not significantly different than the
      UMC group, it was higher and close to the targeted 60% level.* The identified
      findings show that pharmacists' focus on intervention for missed doses, adherence
      and dose adjustment provide positive impact on patients' warfarin therapy.

PMID- 29170636
TI  - Assessing Executive Dysfunction in Neurodegenerative Disorders: A Critical Review
      of Brief Neuropsychological Tools.
AB  - Executive function (EF) has been defined as a multifaceted construct that
      involves a variety of high-level cognitive abilities such as planning, working
      memory, mental flexibility, and inhibition. Being able to identify deficits in EF
      is important for the diagnosis and monitoring of several neurodegenerative
      disorders, and thus their assessment is a topic of much debate. In particular,
      there has been a growing interest in the development of neuropsychological
      screening tools that can potentially provide a reliable quick measure of EF. In
      this review, we critically discuss the four screening tools of EF currently
      available in the literature: Executive Interview-25 (EXIT 25), Frontal Assessment
      Battery (FAB), INECO Frontal Screening (IFS), and FRONTIER Executive Screen
      (FES). We first describe their features, and then evaluate their psychometric
      properties, the existing evidence on their neural correlates, and the empirical
      work that has been conducted in clinical populations. We conclude that the four
      screening tools generally present appropriate psychometric properties, and are
      sensitive to impairments in EF in several neurodegenerative conditions. However,
      more research will be needed mostly with respect to normative data and neural
      correlates, and to determine the extent to which these tools add specific
      information to the one provided by global cognition screening tests. More
      research directly comparing the available tools with each other will also be
      important to establish in which conditions each of them can be most useful.

PMID- 29170638
TI  - Volatile Oil from Amomi Fructus Attenuates 5-Fluorouracil-Induced Intestinal
      Mucositis.
AB  - Amomi Fructus has been used to treat digestive diseases in the context of
      traditional Chinese medicine, so we evaluated the effects of a volatile oil from
      Amomum villosum (VOA) on intestinal mucositis induced by 5-fluorouracil (5-FU).
      We measured the effect of VOA and its main active constituent, bornyl acetate
      (BA), on body weight, food intake, diarrhea, inflammatory cytokines, the mucosal
      barrier, and gut microbiota. VOA and BA significantly increased the rats' body
      weight, relieved diarrhea, and reversed histopathological changes in the gut and
      inflammation. VOA significantly inhibited apoptosis and alleviated the
      endoenteritis by downregulating p38 MAPK and caspase-3 expression. VOA and BA
      strengthened the intestinal mucosal barrier by increasing zonula occludin-1 and
      occludin expression. VOA and BA reduced the amount of pathogenic bacteria and
      increased the abundance of probiotics. Thus, VOA prevented the development and
      progression of intestinal mucositis after chemotherapy.

PMID- 29170639
TI  - A Cell Line for Detection of Botulinum Neurotoxin Type B.
AB  - Botulinum neurotoxins (BoNTs) type A and type B are commonly used as
      biopharmaceutics for neurological diseases, uniquely allowing months-long
      paralysis of target muscles. Their exquisite neuronal specificity is conferred by
      a multistep process of binding, internalization, cytosolic escape and cleavage of
      the neuron-specific proteins, SNAP-25 and vesicle-associated membrane proteins
      (VAMPs), ultimately to inhibit secretion of neurotransmitters. Currently the
      mouse lethality bioassay is the only available method for quality control testing
      of VAMP-cleaving botulinum products. Refined assays for botulinum product testing
      are urgently needed. Specifically, in vitro replacement assays which can account
      for all steps of BoNT intoxication are in high demand. Here, we describe a novel
      SiMa cell-based approach where re-engineering of the VAMP molecule allows
      detection of all BoNT/B intoxication steps using a luminescent enzymatic reaction
      with sensitivity comparable to mouse LD50 bioassay. The presented one-step enzyme
      linked immunosorbent assay meets 3Rs (replacement, reduction, and refinement of
      the use of animals) objectives, is user-friendly and will accelerate development
      of new botulinum drugs. The sensitive enzymatic reporter cell line could also be
      adapted for the detection of toxin activity during the manufacture of botulinum
      and tetanus vaccines.

PMID- 29170640
TI  - Shedding of Microvesicles from Microglia Contributes to the Effects Induced by
      Metabotropic Glutamate Receptor 5 Activation on Neuronal Death.
AB  - Metabotropic glutamate (mGlu) receptor 5 is involved in neuroinflammation and has
      been shown to mediate reduced inflammation and neurotoxicity and to modify
      microglia polarization. On the other hand, blockade of mGlu5 receptor results in
      inhibition of microglia activation. To dissect this controversy, we investigated
      whether microvesicles (MVs) released from microglia BV2 cells could contribute to
      the communication between microglia and neurons and whether this interaction was
      modulated by mGlu5 receptor. Activation of purinergic ionotropic P2X7 receptor
      with the stable ATP analog benzoyl-ATP (100 MUM) caused rapid MVs shedding from
      BV2 cells. Ionic currents through P2X7 receptor increased in BV2 cells pretreated
      for 24 h with the mGlu5 receptor agonist CHPG (200 MUM) as by patch-clamp
      recording. This increase was blunted when microglia cells were activated by
      exposure to lipopolysaccharide (LPS; 0.1 MUg/ml for 6 h). Accordingly, a greater
      amount of MVs formed after CHPG treatment, an effect prevented by the mGlu5
      receptor antagonist MTEP (100 MUM), as measured by expression of flotillin, a
      membrane protein enriched in MVs. Transferred MVs were internalized by SH-SY5Y
      neurons where they did not modify neuronal death induced by a low concentration
      of rotenone (0.1 MUM for 24 h), but significantly increased rotenone
      neurotoxicity when shed from CHPG-treated BV2 cells. miR146a was increased in
      CHPG-treated MVs, an effect concealed in MVs from LPS-activated BV2 cells that
      showed per se an increase in miRNA146a levels. The present data support a role
      for microglia-shed MVs in mGlu5-mediated modulation of neuronal death and
      identify miRNAs as potential critical mediators of this interaction.

PMID- 29170641
TI  - Endothelial Function in Healthy Young Individuals Is Associated with Dietary
      Consumption of Saturated Fat.
AB  - Background: A diet rich in fat, in particular saturated fat (SF), may be linked
      to cardiovascular disease development, possibly due to a detrimental effect of
      fat on endothelial function (EF). Objective: We aimed to determine whether the
      habitual SF intake [as a ratio to total fat (the sum of saturated,
      polyunsaturated, and monounsaturated fat)] might influence endothelial function
      in young, overweight but otherwise healthy adults. Design: Sixty-nine young
      adults (49 males, mean age: 23 +/- 1 years, mean BMI: 29.1 +/- 0.8 kg/m2) were
      classified into three tertiles according to their habitual SF intake consumption
      (low SF: <39%, medium SF 39.1-43.7%, and high SF: >43.7% of total fat).
      Endothelial function was assessed using digital amplitude tonometry. Results: The
      three groups of individuals were comparable for total energy intake and calories
      from: fat, protein, and carbohydrates. There was no difference in anthropometric
      and hemodynamic variables among the groups. Those in the high SF group presented
      with impaired endothelial function [reactive hyperemia index (RHI): high SF: 1.60
      +/- 0.08 compared to 2.23 +/- 0.16 in the medium SF and 2.12 +/- 0.14 in the low
      SF group, P < 0.01]. Regression analysis, including gender, age, ethnicity, body
      mass index indicated that the ratio of SF to total fat was an independent
      predictor of the RHI (P < 0.05). Conclusion: The habitual consumption of a diet
      high in SF in relation to polyunsaturated and monounsaturated fat was strongly
      associated with impaired endothelial function in young overweight adults,
      potentially contributing to increased risk of developing cardiovascular disease.

PMID- 29170643
TI  - Combining Mass Spectrometry and X-Ray Crystallography for Analyzing Native-Like
      Membrane Protein Lipid Complexes.
AB  - Membrane proteins represent a challenging family of macromolecules, particularly
      related to the methodology aimed at characterizing their three-dimensional
      structure. This is mostly due to their amphipathic nature as well as requirements
      of ligand bindings to stabilize or control their function. Recently, Mass
      Spectrometry (MS) has become an important tool to identify the overall
      stoichiometry of native-like membrane proteins complexed to ligand bindings as
      well as to provide insights into the transport mechanism across the membrane,
      with complementary information coming from X-ray crystallography. This
      perspective article emphasizes MS findings coupled with X-ray crystallography in
      several membrane protein lipid complexes, in particular transporters, ion
      channels and molecular machines, with an overview of techniques that allows a
      more thorough structural interpretation of the results, which can help us to
      unravel hidden mysteries on the membrane protein function.

PMID- 29170642
TI  - Muscle Non-shivering Thermogenesis and Its Role in the Evolution of Endothermy.
AB  - The development of sustained, long-term endothermy was one of the major
      transitions in the evolution of vertebrates. Thermogenesis in endotherms does not
      only occur via shivering or activity, but also via non-shivering thermogenesis
      (NST). Mammalian NST is mediated by the uncoupling protein 1 in the brown adipose
      tissue (BAT) and possibly involves an additional mechanism of NST in skeletal
      muscle. This alternative mechanism is based on Ca2+-slippage by a sarcoplasmatic
      reticulum Ca2+-ATPase (SERCA) and is controlled by the protein sarcolipin. The
      existence of muscle based NST has been discussed for a long time and is likely
      present in all mammals. However, its importance for thermoregulation was
      demonstrated only recently in mice. Interestingly, birds, which have evolved from
      a different reptilian lineage than mammals and lack UCP1-mediated NST, also
      exhibit muscle based NST under the involvement of SERCA, though likely without
      the participation of sarcolipin. In this review we summarize the current
      knowledge on muscle NST and discuss the efficiency of muscle NST and BAT in the
      context of the hypothesis that muscle NST could have been the earliest mechanism
      of heat generation during cold exposure in vertebrates that ultimately enabled
      the evolution of endothermy. We suggest that the evolution of BAT in addition to
      muscle NST was related to heterothermy being predominant among early endothermic
      mammals. Furthermore, we argue that, in contrast to small mammals, muscle NST is
      sufficient to maintain high body temperature in birds, which have enhanced
      capacities to fuel muscle NST by high rates of fatty acid import.

PMID- 29170644
TI  - An Overt Chemical Protective Garment Reduces Thermal Strain Compared with a
      Covert Garment in Warm-Wet but Not Hot-Dry Environments.
AB  - Objectives: A commercial chemical, biological, radiological and nuclear (CBRN)
      protective covert garment has recently been developed with the aim of reducing
      thermal strain. A covert CBRN protective layer can be worn under other clothing,
      with equipment added for full chemical protection when needed. However, it is
      unknown whether the covert garment offers any alleviation to thermal strain
      during work compared with a traditional overt ensemble. Therefore, the aim of
      this study was to compare thermal strain and work tolerance times during work in
      an overt and covert ensemble offering the same level of CBRN protection. Methods:
      Eleven male participants wore an overt (OVERT) or covert (COVERT) CBRN ensemble
      and walked (4 km.h-1, 1% grade) for a maximum of 120 min in either a wet bulb
      globe temperature [WBGT] of 21, 30, or 37 degrees C (Neutral, WarmWet and HotDry,
      respectively). The trials were ceased if the participants' gastrointestinal
      temperature reached 39 degrees C, heart rate reached 90% of maximum, walking time
      reached 120 min or due to self-termination. Results: All participants completed
      120 min of walking in Neutral. Work tolerance time was greater in OVERT compared
      with COVERT in WarmWet (P < 0.001, 116.5[9.9] vs. 88.9[12.2] min, respectively),
      though this order was reversed in HotDry (P = 0.003, 37.3[5.3] vs. 48.4[4.6] min,
      respectively). The rate of change in mean body temperature and mean skin
      temperature was greater in COVERT (0.025[0.004] and 0.045[0.010] degrees C.min-1,
      respectively) compared with OVERT (0.014[0.004] and 0.027[0.007] degrees C.min-1,
      respectively) in WarmWet (P < 0.001 and P = 0.028, respectively). However, the
      rate of change in mean body temperature and mean skin temperature was greater in
      OVERT (0.068[0.010] and 0.170[0.026] degrees C.min-1, respectively) compared with
      COVERT (0.059[0.004] and 0.120[0.017] degrees C.min-1, respectively) in HotDry (P
      = 0.002 and P < 0.001, respectively). Thermal sensation, thermal comfort, and
      ratings of perceived exertion did not differ between garments at trial cessation
      (P > 0.05). Conclusion: Those dressed in OVERT experienced lower thermal strain
      and longer work tolerance times compared with COVERT in a warm-wet environment.
      However, COVERT may be an optimal choice in a hot-dry environment. These findings
      have practical implications for those making decisions on the choice of CBRN
      ensemble to be used during work.

PMID- 29170646
TI  - Attention-Deficit/Hyperactivity Disorder And Inflammation: What Does Current
      Knowledge Tell Us? A Systematic Review.
AB  - Background: Attention-deficit/hyperactivity disorder (ADHD) is a complex
      condition that interferes with development and/or functioning. Our objective is
      to investigate the potential association between ADHD and inflammation. Methods:
      We conducted a systematic review of human studies measuring inflammatory markers
      in ADHD. The studies were identified by searching PUBMED, MEDLINE, EMBASE,
      PSYCHINFO, COCHRANE, and SCOPUS databases for peer-reviewed journals published
      until September 2016. We included cytokine gene expression and protein measured.
      Fourteen papers met the inclusion criteria. Results: Seven studies evaluated the
      association of cytokine gene polymorphisms in ADHD, and six studies measured
      cytokines levels in blood. One study analyzed the presence of cytokines in
      cerebrospinal fluid in patients with ADHD. Altogether, these studies indicate a
      possible role of inflammation in ADHD pathogenesis, despite the significant
      heterogeneity and contradictory results. Conclusion: Evidence points to the
      association of ADHD with inflammatory processes, but more studies are warranted.

PMID- 29170645
TI  - Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on
      Place Navigation.
AB  - Muscarinic acetylcholine receptors (mAChRs) have been found to regulate many
      diverse functions, ranging from motivation and feeding to spatial navigation, an
      important and widely studied type of cognitive behavior. Systemic administration
      of non-selective antagonists of mAChRs, such as scopolamine or atropine, have
      been found to have adverse effects on a vast majority of place navigation tasks.
      However, many of these results may be potentially confounded by disruptions of
      functions other than spatial learning and memory. Although studies with selective
      antimuscarinics point to mutually opposite effects of M1 and M2 receptors, their
      particular contribution to spatial cognition is still poorly understood, partly
      due to a lack of truly selective agents. Furthermore, constitutive knock-outs do
      not always support results from selective antagonists. For modeling impaired
      spatial cognition, the scopolamine-induced amnesia model still maintains some
      limited validity, but there is an apparent need for more targeted approaches such
      as local intracerebral administration of antagonists, as well as novel techniques
      such as optogenetics focused on cholinergic neurons and chemogenetics aimed at
      cells expressing metabotropic mAChRs.

PMID- 29170647
TI  - Writing System Modulates the Association between Sensitivity to Acoustic Cues in
      Music and Reading Ability: Evidence from Chinese-English Bilingual Children.
AB  - Music and language share many attributes and a large body of evidence shows that
      sensitivity to acoustic cues in music is positively related to language
      development and even subsequent reading acquisition. However, such association
      was mainly found in alphabetic languages. What remains unclear is whether
      sensitivity to acoustic cues in music is associated with reading in Chinese, a
      morphosyllabic language. The present study aimed to answer this question by
      measuring music (i.e., musical metric perception and pitch discrimination),
      language (i.e., phonological awareness, lexical tone sensitivity), and reading
      abilities (i.e., word recognition) among 54 third-grade Chinese-English bilingual
      children. After controlling for age and non-verbal intelligence, we found that
      both musical metric perception and pitch discrimination accounted for unique
      variance of Chinese phonological awareness while pitch discrimination rather than
      musical metric perception predicted Chinese lexical tone sensitivity. More
      importantly, neither musical metric perception nor pitch discrimination was
      associated with Chinese reading. As for English, musical metric perception and
      pitch discrimination were correlated with both English phonological awareness and
      English reading. Furthermore, sensitivity to acoustic cues in music was
      associated with English reading through the mediation of English phonological
      awareness. The current findings indicate that the association between sensitivity
      to acoustic cues in music and reading may be modulated by writing systems. In
      Chinese, the mapping between orthography and phonology is not as transparent as
      in alphabetic languages such as English. Thus, this opaque mapping may alter the
      auditory perceptual sensitivity in music to Chinese reading.

PMID- 29170648
TI  - One Big Happy Family? Unraveling the Relationship between Shared Perceptions of
      Team Psychological Contracts, Person-Team Fit and Team Performance.
AB  - With the knowledge that team work is not always associated with high(er)
      performance, we draw from the Multi-Level Theory of Psychological Contracts,
      Person-Environment Fit Theory, and Optimal Distinctiveness Theory to study shared
      perceptions of psychological contract (PC) breach in relation to shared
      perceptions of complementary and supplementary fit to explain why some teams
      perform better than other teams. We collected three repeated survey measures in a
      sample of 128 respondents across 46 teams. After having made sure that we met all
      statistical criteria, we aggregated our focal variables to the team-level and
      analyzed our data by means of a longitudinal three-wave autoregressive moderated
      mediation model in which each relationship was one-time lag apart. We found that
      shared perceptions of PC breach were directly negatively related to team output
      and negatively related to perceived team member effectiveness through a decrease
      in shared perceptions of supplementary fit. However, we also demonstrated a
      beneficial process in that shared perceptions of PC breach were positively
      related to shared perceptions of complementary fit, which in turn were positively
      related to team output. Moreover, best team output appeared in teams that could
      combine high shared perceptions of complementary fit with modest to high shared
      perceptions of supplementary fit. Overall, our findings seem to indicate that in
      terms of team output there may be a bright side to perceptions of PC breach and
      that perceived person-team fit may play an important role in this process.

PMID- 29170649
TI  - Does the Effort of Processing Potential Incentives Influence the Adaption of
      Context Updating in Older Adults?
AB  - A number of aging studies suggest that older adults process positive and negative
      information differently. For instance, the socioemotional selectivity theory
      postulates that older adults preferably process positive information in service
      of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research
      has started to investigate whether incentives like gains or losses can influence
      cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015),
      we examined whether incentive cues, indicating potential monetary gains, losses,
      or neutral outcomes for good performance in the following trial, would influence
      older adults' ability to exert cognitive control. Cognitive control was measured
      in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select
      their responses to probe stimuli depending on a preceding context cue. In this
      study, we did not find support for a positivity effect in older adults, but both
      gains and losses led to enhanced context processing. As the trial-wise
      presentation mode may be too demanding on cognitive resources for such a bias to
      occur, the main goal of the present study was to examine whether motivational
      mindsets, induced by block-wise presentation of incentives, would result in a
      positivity effect. For this reason, we examined 17 older participants (65-76
      years) in the AX-CPT using a block-wise presentation of incentive cues and
      compared them to 18 older adults (69-78 years) with the trial-wise presentation
      mode from our earlier study (Schmitt et al., 2015). Event-related potentials were
      recorded to the onset of the motivational cue and during the AX-CPT. Our results
      show that (a) older adults initially process cues signaling potential losses more
      strongly, but later during the AX-CPT invest more cognitive resources in
      preparatory processes like context updating in conditions with potential gains,
      and (b) block-wise and trial-wise presentation of incentive cues differentially
      influenced cognitive control. When incentives were presented block-wise, the
      above described valence effects were consistently found. In contrast, when
      incentives were presented trial-wise, the effects were mixed and salience as well
      as valence effects can be obtained. Hence, how positive and negative incentive
      cues influence cognitive control in older adults is dependent on demands of cue
      processing.

PMID- 29170650
TI  - Eye Movements in Parkinson's Disease and Inherited Parkinsonian Syndromes.
AB  - Despite extensive research, the functions of the basal ganglia (BG) in movement
      control have not been fully understood. Eye movements, particularly saccades, are
      convenient indicators of BG function. Here, we review the main oculomotor
      findings reported in Parkinson's disease (PD) and genetic parkinsonian syndromes.
      PD is a progressive, neurodegenerative disorder caused by dopaminergic cell loss
      within the substantia nigra pars compacta, resulting in depletion of striatal
      dopamine and subsequent increased inhibitory BG output from the internal globus
      pallidus and the substantia nigra pars reticulata. Eye movement abnormalities are
      common in PD: anomalies are more evident in voluntary than reflexive saccades in
      the initial stages, but visually guided saccades may also be involved at later
      stages. Saccadic hypometria (including abnormally fragmented saccades), reduced
      accuracy, and increased latency are among the most prominent deficits. PD
      patients show also unusually frequent and large square wave jerks and impaired
      inhibition of reflexive saccades when voluntary mirror saccades are required.
      Poor convergence ability and altered pursuit are common. Inherited parkinsonisms
      are a heterogeneous group of rare syndromes due to gene mutations causing
      symptoms resembling those of PD. Eye movement characteristics of some
      parkinsonisms have been studied. While sharing some PD features, each syndrome
      has a distinctive profile that could contribute to better define the clinical
      phenotype of parkinsonian disorders. Moreover, because the pathogenesis and the
      underlying neural circuit failure of inherited parkinsonisms are often well
      defined, they might offer a better prospect than idiopathic PD to understand the
      BG function.

PMID- 29170651
TI  - The Spatial Associations of Cerebral Blood Flow and Spontaneous Brain Activities
      with White Matter Hyperintensities-An Exploratory Study Using Multimodal Magnetic
      Resonance Imaging.
AB  - White matter hyperintensities (WMHs) have been reported to be correlated with
      functional brain changes, but the association of the specific WMHs distribution
      pattern with regional functional changes remains uncertain. The aim of this study
      is to explore the possible spatial correlation of WMH with changes in cerebral
      blood flow (CBF) and spontaneous brain activities in elderly using a novel
      approach. The WMHs, CBF, and spontaneous brain activities measured by intrinsic
      connectivity contrast (ICC), were quantified using multimodal magnetic resonance
      imaging for 69 elderly subjects. Such approach enables us to expand our search
      for newly identified correlated areas by drawing strengths of different modes and
      provides a means for triangulation as well as complementary insights. The results
      showed significant positive correlations between WMH volumes in the right
      superior corona radiata and CBF in the left supplementary motor area, as well as
      between WMH volumes in left anterior limb internal capsule and CBF in the right
      putamen. Significant correlations of regional WMH volumes and ICC were also
      detected between the right anterior corona radiata and the left cuneus, and the
      right superior occipital cortex, as well as between the right superior corona
      radiata and the left superior occipital cortex. These findings may suggest a
      regional compensatory functional enhancement accounting for the maintenance of
      cognitively normal status, which can be supported by the widely observed
      phenomenon that mild to moderate WMH load could have little effect on global
      cognitive performance.

PMID- 29170652
TI  - Characteristic Eye Movements in Ataxia-Telangiectasia-Like Disorder: An
      Explanatory Hypothesis.
AB  - Objective: To investigate cerebellar dysfunctions and quantitatively characterize
      specific oculomotor changes in ataxia-telangiectasia-like disorder (ATLD), a rare
      autosomal recessive disease caused by mutations in the MRE11 gene. Additionally,
      to further elucidate the pathophysiology of cerebellar damage in the ataxia
      telangiectasia (AT) spectrum disorders. Methods: Saccade dynamics, metrics, and
      visual fixation deficits were investigated in two Italian adult siblings with
      genetically confirmed ATLD. Visually guided saccades were compared with those of
      40 healthy subjects. Steady fixation was tested in primary and eccentric
      positions. Quantitative characterization of saccade parameters, saccadic
      intrusions (SI), and nystagmus was performed. Results: Patients showed abnormally
      hypermetric and fast horizontal saccades to the left and greater inaccuracy than
      healthy subjects in all saccadic eye movements. Eye movement abnormalities
      included slow eye movements that preceded the initial saccade. Horizontal and
      vertical spontaneous jerk nystagmus, gaze-evoked, and rebound nystagmus were
      evident. Fixation was interrupted by large square-wave jerk SI and macrosaccadic
      oscillations. Conclusion: Slow eye movements accompanying saccades, SI, and
      cerebellar nystagmus are frequently seen in AT patients, additionally our ATLD
      patients showed the presence of fast and hypermetric saccades suggesting damage
      of granule cell-parallel fiber-Purkinje cell synapses of the cerebellar vermis. A
      dual pathogenetic mechanism involving neurodevelopmental and neurodegenerative
      changes is hypothesized to explain the peculiar phenotype of this disease.

PMID- 29170653
TI  - The Association of Thyroid Disease and Oral Lichen Planus: A Literature Review
      and Meta-analysis.
AB  - Background: The objective of this study was to systemically evaluate the
      association between oral lichen planus (OLP) and thyroid disease. Method: Eleven
      electronic databases were searched for any clinical study published up until
      August 2016 that explored an association between OLP and thyroid disease,
      complemented with manual searching. The titles and abstracts of all studies
      identified from the electronic searches were then assessed independently to
      determine inclusion of the study. The population of interest was patients with
      OLP, and the exposure was the presence of thyroid disease in OLP patients.
      Statistical analyses were conducted using Review Manager 5.2. The odds ratios
      (OR) and 95% confidence intervals (CIs) were calculated to evaluate the
      association between OLP and thyroid disease. Results: Eight studies were included
      for review, and of these, four case-control studies were included in the final
      meta-analysis. The mean Newcastle-Ottawa Scale score evaluating the
      methodological quality of the four studies was 6.5. The OR was 2.10 (95% CI: 1.47
      3.01), indicating a statistically significant difference in the prevalence of
      thyroid disease between the OLP and control groups. Heterogeneity was
      satisfactory (I2 = 0%, <25%). An approximately symmetrical funnel plot suggested
      no obvious publication bias. Two articles showed a higher correlation between OLP
      and hypothyroidism (OR 1.83, 95% CI: 1.16-2.89), with satisfactory heterogeneity
      (I2 = 0%, <25%). Conclusion: This meta-analysis indicated a significantly high
      prevalence of thyroid disease among OLP patients compared with controls,
      suggesting that routine screening for thyroid disease could be beneficial to OLP
      patients. However, due to the small number of studies included, further studies
      are needed to confirm the results.

PMID- 29170654
TI  - Preparation and Characterization of Enzyme Compartments in UV-Cured Polyurethane
      Based Materials and Their Application in Enzymatic Reactions.
AB  - The preparation and characterization of UV-cured polyurethane-based materials for
      the mild inclusion immobilization of enzymes was investigated. Full curing of the
      polymer precursor/enzyme solution mixture was realized by a short irradiation
      with UV-light at ambient temperatures. The included aqueous enzyme solution
      remains highly dispersed in the polymer material with an even size distribution
      throughout the polymer material. The presented concept provides stable enzyme
      compartments which were applied for an alcohol dehydrogenase-catalyzed reduction
      reaction in organic solvents. Cofactor regeneration was achieved by a substrate
      coupled approach via 2-propanol or an enzyme-coupled approach by a glucose
      dehydrogenase. This reaction concept can also be used for a simultaneous
      application of contrary biocatalytic reaction conditions within an enzymatic
      cascade reaction. Independent polymer-based reaction compartments were provided
      for two incompatible enzymatic reaction systems (alcohol dehydrogenase and
      hydroxynitrile lyase), while the relevant reactants diffuse between the applied
      compartments.

PMID- 29170655
TI  - The TAL Effector AvrBs3 from Xanthomonas campestris pv. vesicatoria Contains
      Multiple Export Signals and Can Enter Plant Cells in the Absence of the Type III
      Secretion Translocon.
AB  - Pathogenicity of the Gram-negative plant-pathogenic bacterium Xanthomonas
      campestris pv. vesicatoria depends on a type III secretion (T3S) system which
      translocates effector proteins into plant cells. Effector protein delivery is
      controlled by the T3S chaperone HpaB, which presumably escorts effector proteins
      to the secretion apparatus. One intensively studied effector is the transcription
      activator-like (TAL) effector AvrBs3, which binds to promoter sequences of plant
      target genes and activates plant gene expression. It was previously reported that
      type III-dependent delivery of AvrBs3 depends on the N-terminal protein region.
      The signals that control T3S and translocation of AvrBs3, however, have not yet
      been characterized. In the present study, we show that T3S and translocation of
      AvrBs3 depend on the N-terminal 10 and 50 amino acids, respectively. Furthermore,
      we provide experimental evidence that additional signals in the N-terminal 30
      amino acids and the region between amino acids 64 and 152 promote translocation
      of AvrBs3 in the absence of HpaB. Unexpectedly, in vivo translocation assays
      revealed that AvrBs3 is delivered into plant cells even in the absence of HrpF,
      which is the predicted channel-forming component of the T3S translocon in the
      plant plasma membrane. The presence of HpaB- and HrpF-independent transport
      routes suggests that the delivery of AvrBs3 is initiated during early stages of
      the infection process, presumably before the activation of HpaB or the insertion
      of the translocon into the plant plasma membrane.

PMID- 29170656
TI  - Double-Face Meets the Bacterial World: The Opportunistic Pathogen
      Stenotrophomonas maltophilia.
AB  - Most studies on bacterial virulence focus on the pathogen itself. However, it is
      important to recall that the in-host behavior and the virulence of bacterial
      pathogens constitute a complex situation that depends on both the microorganisms
      and the infected host. While healthy people (the community) is infected by
      classical pathogenic microorganisms, able to cope with the anti-infection
      defenses of the host, in the case of people with basal diseases, debilitated or
      immunodepressed, the range of pathogens able to cause infection is wider and
      includes the so-named opportunistic pathogens, which lack the inherent ability to
      cause disease in healthy hosts and rarely produce infections in the community.
      Some of the most relevant opportunistic pathogens, as Stenotrophomonas
      maltophilia, have an environmental origin and, in occasions, present interesting
      biotechnological properties. Consequently, it is important knowing whether S.
      maltophilia isolates recovered from infections constitute a specific phylogenetic
      branch that has evolved toward acquiring a virulent phenotype as it happens in
      the case of classical pathogens or rather, any member of this bacterial species
      is capable of producing infection and its pathogenic behavior is mainly a
      consequence of the host situation. To address this question, we analyzed a set of
      environmental and clinical S. maltophilia strains. Our results indicate that this
      opportunistic pathogen presents a large core genome and that the distribution of
      genes in general, and of known virulence determinants in particular, is similar
      among environmental and clinical isolates. The majority of genes not belonging to
      the S. maltophilia core genome are present in just one or two of the analyzed
      strains. This indicates that, more than speciation into different lineages
      (virulent and environmental), the evolution of S. maltophilia is based in the
      strain-specific acquisition of genes, likely involved in the adaptation of this
      bacterial species to different microniches. In addition, both environmental and
      clinical isolates present low susceptibility to several antimicrobials.
      Altogether our results support that S. maltophilia does not present a specific
      evolutionary branch toward virulence and most likely infection is mainly the
      consequence of the impaired anti-infective response of the infected patients.

PMID- 29170657
TI  - Fitness Cost of Daptomycin-Resistant Staphylococcus aureus Obtained from in Vitro
      Daptomycin Selection Pressure.
AB  - Daptomycin-resistant (DAP-R) Staphylococcus aureus strains are well documented,
      but have not been reported in China. To elucidate the evolution adaptability and
      fitness cost of DAP-R S. aureus, three DAP susceptible strains, Pre3 (MRSA, ST239
      t037), Pre5 (MRSA, ST239-t037), and Pre14b (MSSA, ST188-t189), were isolated from
      patients with bloodstream infections, and serially passaged in Mueller-Hinton
      broth with a gradient of DAP concentration to select for resistance. Highly DAP-R
      mutants were obtained after screening for 34 passages. The DAP minimum inhibitory
      concentrations increased from 0.5 MUg/ml in the parent strains to 16 MUg/ml in
      the mutants, which remained tolerant to 4 MUg/ml of DAP for more than 160
      generations. The growth of the three mutant strains was slower than that of the
      parent strains, with relative fitness cost of 34.8%, 19.2%, and 15.0%,
      respectively. The in vitro serum tolerance of the mutants was decreased, and the
      lethality and pathogenicity in mice were weakened (P < 0.01). Transmission
      electron microscopy found that the cell walls of the mutants were significantly
      thicker (from 38.6% to 75.4%) than those of the parent cells. Mutation L826F of
      mprF was found in Post14b, G299V, and L473I of mprF and Y225N of walK were found
      in Post3, while T345A of mprF, S52N of graS, and F473I of walK were found in
      Post5. Thus, stable DAP-R mutants could be obtained from a middle-short term of
      in vitro DAP selection, and according to their fitness cost, some prevention and
      control work may be done to cope with DAP-R S. aureus that may appear in China in
      the future.

PMID- 29170658
TI  - Fungal Community Structure and As-Resistant Fungi in a Decommissioned Gold Mine
      Site.
AB  - Although large quantities of heavy metal laden wastes are released in an
      uncontrolled manner by gold mining activities with ensuing contamination of the
      surrounding areas, there is scant information on the mycobiota of gold-mine
      sites. Thus, the present study was aimed to describe the fungal community
      structure in three differently As- and Hg-polluted soils collected from the
      Pestarena decommissioned site by using Illumina(r) metabarcoding. Fungal richness
      was found to increase as the contamination level increased while biodiversity was
      not related to the concentrations of inorganic toxicants. Within the phylum
      Zygomigota which, irrespective of the contamination level, was predominant in all
      the soils under study, the most abundant genera were Mucor and Mortierella. The
      relative abundances of Basidiomycota, instead, tended to raise as the
      contamination increased; within this phylum the most abundant genera were
      Cryptococcus and Pseudotomentella. The abundance of Ascomycota, ranging from
      about 8 to 21%, was not related to the contamination level. The relative
      abundances of those genera (i.e., Penicillium, Trichoderma, and Chaetomium), the
      cultivable isolates of which exhibited significant As-resistance, were lower than
      the set threshold (0.5%). Mass balances obtained from As-exposure experiments
      with these isolates showed that the main mechanisms involved in counteracting the
      toxicant were accumulation and, above all, volatilization, the respective extents
      of which ranged from 0.6 to 5.9% and from 6.4 to 31.2% in dependence of the
      isolate.

PMID- 29170659
TI  - Geochemical Influence on Microbial Communities at CO2-Leakage Analog Sites.
AB  - Microorganisms influence the chemical and physical properties of subsurface
      environments and thus represent an important control on the fate and
      environmental impact of CO2 that leaks into aquifers from deep storage
      reservoirs. How leakage will influence microbial populations over long time
      scales is largely unknown. This study uses natural analog sites to investigate
      the long-term impact of CO2 leakage from underground storage sites on subsurface
      biogeochemistry. We considered two sites with elevated CO2 levels (sample groups
      I and II) and one control site with low CO2 content (group III). Samples from
      sites with elevated CO2 had pH ranging from 6.2 to 4.5 and samples from the low
      CO2 control group had pH ranging from 7.3 to 6.2. Solute concentrations were
      relatively low for samples from the control group and group I but high for
      samples from group II, reflecting varying degrees of water-rock interaction.
      Microbial communities were analyzed through clone library and MiSeq sequencing.
      Each 16S rRNA analysis identified various bacteria, methane-producing archaea,
      and ammonia-oxidizing archaea. Both bacterial and archaeal diversities were low
      in groundwater with high CO2 content and community compositions between the
      groups were also clearly different. In group II samples, sequences classified in
      groups capable of methanogenesis, metal reduction, and nitrate reduction had
      higher relative abundance in samples with relative high methane, iron, and
      manganese concentrations and low nitrate levels. Sequences close to
      Comamonadaceae were abundant in group I, while the taxa related to methanogens,
      Nitrospirae, and Anaerolineaceae were predominant in group II. Our findings
      provide insight into subsurface biogeochemical reactions that influence the
      carbon budget of the system including carbon fixation, carbon trapping, and CO2
      conversion to methane. The results also suggest that monitoring groundwater
      microbial community can be a potential tool for tracking CO2 leakage from
      geologic storage sites.

PMID- 29170660
TI  - Effect of Dietary Forage to Concentrate Ratios on Dynamic Profile Changes and
      Interactions of Ruminal Microbiota and Metabolites in Holstein Heifers.
AB  - A better understanding of global ruminal microbiota and metabolites under
      extensive feeding conditions is a prerequisite for optimizing rumen function and
      improving ruminant feed efficiency. Furthermore, the gap between the information
      on the ruminal microbiota and metabolites needs to be bridged. The aim of this
      study was to investigate the effects of a wide range of forage to concentrate
      ratios (F:C) on changes and interactions of ruminal microbiota and metabolites.
      Four diets with different F:C (80:20, 60:40, 40:60, and 20:80) were limit-fed to
      24 Holstein heifers, and Illumina MiSeq sequencing and gas chromatography time-of
      flight/mass spectrometry were used to investigate the profile changes of the
      ruminal microbes and metabolites, and the interaction between them. The
      predominant bacterial phyla in the rumen were Bacteroidetes (57.2 +/- 2.6%) and
      Firmicutes (26.8 +/- 1.6%), and the predominant anaerobic fungi were
      Neocallimastigomycota (64.3 +/- 3.8%) and Ascomycota (22.6 +/- 2.4%). In total,
      44, 9, 25, and 2 genera, respectively, were identified as the core rumen
      bacteria, ciliate protozoa, anaerobic fungi, and archaea communities across all
      samples. An increased concentrate level linearly decreased the relative abundance
      of cellulolytic bacteria and ciliates, namely Fibrobacter, Succinimonas,
      Polyplastron, and Ostracodinium (q < 0.05), and linearly increased the relative
      abundance of Entodinium (q = 0.04), which is a non-fibrous carbohydrate degrader.
      Dietary F:C had no effect on the communities of anaerobic fungi and archaea.
      Rumen metabolomics analysis revealed that ruminal amino acids, lipids, organic
      acids, and carbohydrates were altered significantly by altering the dietary F:C.
      With increasing dietary concentrate levels, the proportions of propionate and
      butyrate linearly increased in the rumen (P <= 0.01). Correlation analysis
      revealed that there was some utilization relationship or productive association
      between candidate metabolites and affected microbe groups. This study provides a
      better understanding of ruminal microbiota and metabolites under a wide range of
      dietary F:C, which could further reveal integrative information of rumen function
      and lead to an improvement in ruminant production.

PMID- 29170661
TI  - Trade, Diplomacy, and Warfare: The Quest for Elite Rhizobia Inoculant Strains.
AB  - Rhizobia form symbiotic nitrogen-fixing nodules on leguminous plants, which
      provides an important source of fixed nitrogen input into the soil ecosystem. The
      improvement of symbiotic nitrogen fixation is one of the main challenges facing
      agriculture research. Doing so will reduce the usage of chemical nitrogen
      fertilizer, contributing to the development of sustainable agriculture practices
      to deal with the increasing global human population. Sociomicrobiological studies
      of rhizobia have become a model for the study of the evolution of mutualistic
      interactions. The exploitation of the wide range of social interactions rhizobia
      establish among themselves, with the soil and root microbiota, and with the host
      plant, could constitute a great advantage in the development of a new generation
      of highly effective rhizobia inoculants. Here, we provide a brief overview of the
      current knowledge on three main aspects of rhizobia interaction: trade of fixed
      nitrogen with the plant; diplomacy in terms of communication and possible
      synergistic effects; and warfare, as antagonism and plant control over symbiosis.
      Then, we propose new areas of investigation and the selection of strains based on
      the combination of the genetic determinants for the relevant rhizobia symbiotic
      behavioral phenotypes.

PMID- 29170662
TI  - Salmonella in Peripheral Lymph Nodes of Healthy Cattle at Slaughter.
AB  - To more fully characterize the burden of Salmonella enterica in bovine peripheral
      lymph nodes (PLN), PLN (n = 5,450) were collected from healthy cattle at
      slaughter in 12 commercial abattoirs that slaughtered feedlot-fattened (FF)
      cattle exclusively (n = 7), cattle removed (or culled) from breeding herds (n =
      3), or both FF and cull cattle (n = 2). Qualitative and quantitative methods were
      used to estimate prevalence and concentration of Salmonella in PLN. Isolates were
      subjected to a variety of phenotypic, serological, and molecular assays. Overall,
      Salmonella prevalence in PLN from FF and cull cattle was 7.1 and 1.8%. However,
      burden varied by season in that observed prevalence in PLN collected in cooler or
      warmer seasons was 2.4 and 8.2%, respectively. Prevalence in PLN from cull cattle
      in the southwest region of the US was 2.1 and 1.1% for cool and warm seasons,
      respectively; however, prevalence in FF PLN was far greater in that it was 6.5
      and 31.1%, respectively. Salmonella was recovered from 289 (5.6%) PLN and 2.9% (n
      = 160) of all PLN tested had quantifiable concentrations that varied from 1.6 to
      4.9 log10 colony forming units/PLN. The most common serotypes isolated from PLN
      were Montevideo (26.9%), Lille (14.9%), Cerro (13.0%), Anatum (12.8%), and Dublin
      (6.9%). In all, 376 unique isolates were collected from the 289 Salmonella
      positive PLN. Antimicrobial susceptibility testing revealed the majority (80.6%)
      of these isolates were pansusceptible; however, 10.7% of isolates were found to
      be resistant to two or more antimicrobial classes. We were able to document an
      observed increased in prevalence of Salmonella in PLN during the warmer season,
      particularly in FF cattle from the southwest region of the US. The mechanisms
      underlying the observed association between season, region, and production source
      have yet to be elucidated. Nevertheless, these findings increase our
      understanding of the sources of contamination of beef products and shed light on
      transmission dynamics that may be useful in targeting these sources.

PMID- 29170663
TI  - Neutrophil Functional Heterogeneity: Identification of Competitive Phagocytosis.
AB  - Introduction: Phagocytosis by neutrophils is a key process in the innate immune
      response against invading microorganisms. Despite reported heterogeneity in other
      neutrophils functions, little is known regarding differences in phagocytosis by
      individual cells. Therefore, we tested the hypothesis that heterogeneity is
      present in the neutrophil compartment in its potency to phagocytize bacteria.
      Methods: Phagocytosis assays were performed in suspension with isolated
      neutrophils and Staphylococcus aureus expressing different fluorescent proteins
      at MOIs between 1 and 10. Repetitive addition of bacteria with different
      fluorescent proteins and MOIs was used to compare the phagocytic capacity of S.
      aureus-green fluorescent protein (GFP)-positive and negative neutrophils and
      exclude randomness. Results: The percentage and mean fluorescence intensity (MFI)
      of S. aureus-GFP-positive neutrophils increased with higher MOIs. The increase in
      MFI was due to phagocytosis of multiple bacteria per neutrophil as was confirmed
      by confocal imaging. Sequential phagocytosis of GFP- and mCherry-expressing S.
      aureus showed a non-random process, as S. aureus-GFP-positive neutrophils
      preferentially phagocytized S. aureus-mCherry. Conclusion: All neutrophils were
      able to phagocytize S. aureus, but some were much more potent than others.
      Therefore, at physiologically relevant MOIs these potent phagocytizing
      neutrophils will outcompete the uptake of bacteria by less competent cells in a
      process we propose to name "competitive phagocytosis."

PMID- 29170664
TI  - The Intra-Dependence of Viruses and the Holobiont.
AB  - Animals live in symbiosis with the microorganisms surrounding them. This
      symbiosis is necessary for animal health, as a symbiotic breakdown can lead to a
      disease state. The functional symbiosis between the host, and associated
      prokaryotes, eukaryotes, and viruses in the context of an environment is the
      holobiont. Deciphering these holobiont associations has proven to be both
      difficult and controversial. In particular, holobiont association with viruses
      has been of debate even though these interactions have been occurring since
      cellular life began. The controversy stems from the idea that all viruses are
      parasitic, yet their associations can also be beneficial. To determine viral
      involvement within the holobiont, it is necessary to identify and elucidate the
      function of viral populations in symbiosis with the host. Viral metagenome
      analyses identify the communities of eukaryotic and prokaryotic viruses that
      functionally associate within a holobiont. Similarly, analyses of the host in
      response to viral presence determine how these interactions are maintained.
      Combined analyses reveal how viruses interact within the holobiont and how viral
      symbiotic cooperation occurs. To understand how the holobiont serves as a
      functional unit, one must consider viruses as an integral part of disease,
      development, and evolution.

PMID- 29170665
TI  - Canonical Stimulation of the NLRP3 Inflammasome by Fungal Antigens Links Innate
      and Adaptive B-Lymphocyte Responses by Modulating IL-1beta and IgM Production.
AB  - The NLRP3 inflammasome is activated in response to different bacterial, viral,
      and fungal pathogens and serves as modulator of different pattern recognition
      receptors signaling pathways. One of the main functions of NLRP3 is to
      participate in IL-1beta maturation which is important in the host defense against
      Pneumocystis and other fungal infections. However, dysregulation of NLRP3 and IL
      1beta secretion are also implicated in the pathophysiology of many auto
      inflammatory disorders. Often time's inflammatory flares are preceded by
      infectious illnesses questioning the role of infection in autoimmune
      exacerbations. However, we still do not fully understand the exact role that
      infection or even colonization plays as a trigger of inflammation. Herein, we
      investigated the role of NLRP3 in circulating B-lymphocytes following activation
      with two major microbial antigens (beta-glucan and CpG). NLRP3 was determined
      essential in two independent B-lymphocytes processes: pro-inflammatory cytokine
      secretion and antibody regulation. Our results show that the beta-glucan fungal
      cell wall carbohydrate stimulated B-lymphocytes to secrete IL-1beta in a process
      partially mediated by Dectin-1 activation via SYK and the transcription factors
      NF-kappaB and AP-1. This IL-1beta secretion was regulated by the NLRP3
      inflammasome and was dependent on potassium efflux and Caspase-1. Interestingly,
      B-lymphocytes activated by unmethylated CpG motifs, found in bacterial and fungal
      DNA, failed to induce IL-1beta. However, B-lymphocyte stimulation by CpG resulted
      in NLRP3 and Caspase-1 activation and the production and secretion of IgM
      antibodies. Furthermore, CpG-stimulated IgM secretion, unlike beta-glucan
      mediated IL-1beta production, was mediated by the mammalian target of rapamycin
      (mTOR). Inhibition of NLRP3 and the mTOR pathway in CpG activated B-lymphocytes
      resulted in impaired IgM secretion suggesting their participation in antibody
      regulation. In conclusion, this study describes a differential response of NLRP3
      to beta-glucan and CpG antigens and identifies the NLRP3 inflammasome of human
      circulating B-lymphocytes as a modulator of the innate and adaptive immune
      systems.

PMID- 29170666
TI  - Low T-Cell Responses to Mitogen Stimulation Predicts Poor Survival in Recipients
      of Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - Background: Successful engraftment and reconstitution of the innate and adaptive
      immune system are associated with improved outcomes in recipients of allogeneic
      hematopoietic stem cell transplantation (HSCT). A clinically meaningful and
      simple biomarker of immunosuppression could potentially assist clinicians in
      their decision-making. We aimed to determine the relationship between T-cell
      production of interferon gamma (IFN-gamma) in response to phytohemagglutinin
      (PHA) to clinical outcomes in HSCT recipients. Methods: A prospective
      observational multicenter study of 73 adult allogeneic HSCT recipients was
      conducted in Melbourne, Australia. Eligible participants were >18 years and at
      risk of cytomegalovirus disease. T-cell responses to PHA were assessed at 3, 6,
      9, and 12 months post-HSCT using the commercial quantiferon-cytomegalovirus
      assay, which quantifies IFN-gamma production by ELISA following stimulation with
      PHA. A low response was defined as IFN-gamma <0.5 IU/ml following stimulation
      with PHA. Results: At 3 months post-HSCT, high responses to PHA (median IFN-gamma
      7.68 IU/ml) were seen in 63% of participants and low responses to PHA (median IFN
      gamma 0.06 IU/ml) in 37%. IFN-gamma responses to PHA were significantly
      associated with the severity of acute graft versus host disease (AGVHD) (spearman
      r = -0.53, p < 0.001) and correlated with blood lymphocyte count (spearman r =
      0.52, p < 0.001). Twelve month overall survival was greater in individuals with
      high compared to low IFN-gamma response to PHA at 3 months [92 vs. 62%,
      respectively, Cox proportional hazard ratio (HR): 4.12 95% CI: 1.2-13.7, p =
      0.02]. Non-relapse mortality (NRM) was higher in individuals with low IFN-gamma
      response to PHA (competing risk regression HR 11.6 p = 0.02). In individuals with
      no AGVHD compared to AGVHD and high IFN-gamma response to PHA compared to AGVHD
      and low IFN-gamma response to PHA, 12-month survival was 100 vs. 80 vs. 52%,
      respectively (log rank test p < 0.0001). Conclusion: Low IFN-gamma response to
      PHA at the 3-month time-point following allogeneic HSCT was predictive of reduced
      12-month overall survival, increased NRM, and reduced survival in recipients with
      AGVHD. Assessing IFN-gamma response to PHA post-HSCT may be a clinically useful
      immune biomarker.

PMID- 29170667
TI  - Will a mAb-Based Immunotherapy Directed against Cancer Stem Cells Be Feasible?
AB  - The cancer stem cell (CSC) hypothesis suggests that within a tumor, there is a
      small subpopulation of cells with stem cell properties responsible for tumor
      maintenance and metastasis generation. This hypothesis also implies that new
      antitumor drugs, rather than targeting the bulk of the tumor mass, would be more
      effective if they directly targeted the CSC subpopulation. The CSCs from several
      types of tumors have been identified with mAbs recognizing surface antigens in
      these cells; however, antigens specifically or exclusively expressed in the CSC
      population have not yet been identified. Thus, questioning the possibility of
      using therapeutic antibodies directed against the CSCs. Here, we review the
      possibilities of using antibodies directly targeting the CSCs as therapeutic
      agents in the form of naked antibodies, antibodies conjugated to nanoparticles,
      or antibody cocktails.

PMID- 29170668
TI  - Epitope-Specific Tolerance Modes Differentially Specify Susceptibility to
      Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis.
AB  - Immunization with myelin components can elicit experimental autoimmune
      encephalomyelitis (EAE). EAE susceptibility varies between mouse strains,
      depending on the antigen employed. BL/6 mice are largely resistant to EAE
      induction with proteolipid protein (PLP), probably a reflection of antigen
      specific tolerance. However, the extent and mechanism(s) of tolerance to PLP
      remain unclear. Here, we identified three PLP epitopes in PLP-deficient BL/6
      mice. PLP-sufficient mice did not respond against two of these, whereas tolerance
      was "leaky" for an epitope with weak predicted MHCII binding, and only this
      epitope was encephalitogenic. In TCR transgenic mice, the "EAE-susceptibility
      associated" epitope was "ignored" by specific CD4 T cells, whereas the
      "resistance-associated" epitope induced clonal deletion and Treg induction in the
      thymus. Central tolerance was autoimmune regulator dependent and required
      expression and presentation of PLP by thymic epithelial cells (TECs). TEC
      specific ablation of PLP revealed that peripheral tolerance, mediated by
      dendritic cells through recessive tolerance mechanisms (deletion and anergy),
      could largely compensate for a lack of central tolerance. However, adoptive EAE
      was exacerbated in mice lacking PLP in TECs, pointing toward a non-redundant role
      of the thymus in dominant tolerance to PLP. Our findings reveal multiple layers
      of tolerance to a central nervous system autoantigen that vary among epitopes and
      thereby specify disease susceptibility. Understanding how different modalities of
      tolerance apply to distinct T cell epitopes of a target in autoimmunity has
      implications for antigen-specific strategies to therapeutically interfere with
      unwanted immune reactions against self.

PMID- 29170669
TI  - Introducing Membrane Charge and Membrane Potential to T Cell Signaling.
AB  - While membrane models now include the heterogeneous distribution of lipids, the
      impact of membrane charges on regulating the association of proteins with the
      plasma membrane is often overlooked. Charged lipids are asymmetrically
      distributed between the two leaflets of the plasma membrane, resulting in the
      inner leaflet being negatively charged and a surface potential that attracts and
      binds positively charged ions, proteins, and peptide motifs. These interactions
      not only create a transmembrane potential but they can also facilitate the
      formation of charged membrane domains. Here, we reference fields outside of
      immunology in which consequences of membrane charge are better characterized to
      highlight important mechanisms. We then focus on T cell receptor (TCR) signaling,
      reviewing the evidence that membrane charges and membrane-associated calcium
      regulate phosphorylation of the TCR-CD3 complex and discuss how the immunological
      synapse exhibits distinct patterns of membrane charge distribution. We propose
      that charged lipids, ions in solution, and transient protein interactions form a
      dynamic equilibrium during T cell activation.

PMID- 29170670
TI  - Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated
      Stimulation.
AB  - Linking immunometabolic adaptation to T-cell function provides insight for the
      development of new therapeutic approaches in multiple disease settings. T-cell
      activation and downstream effector functions of CD4+ and CD8+ T-cells are
      controlled by the strength of interaction between the T-cell receptor (TCR) and
      peptides presented by human leukocyte antigens (pHLA). The role of TCR-pHLA
      interactions in modulating T-cell metabolism is unknown. Here, for the first
      time, we explore the relative contributions of the main metabolic pathways to
      functional responses in human CD4+ and CD8+ T-cells. Increased expression of
      hexokinase II accompanied by higher basal glycolysis is demonstrated in CD4+ T
      cells; cytokine production in CD8+ T-cells is more reliant on oxidative
      phosphorylation. Using antigen-specific CD4+ and CD8+ T-cell clones and altered
      peptide ligands, we demonstrate that binding affinity tunes the underlying
      metabolic shift. Overall, this study provides important new insight into how
      metabolic pathways are controlled during antigen-specific activation of human T
      cells.

PMID- 29170671
TI  - B7-H1 Influences the Accumulation of Virus-Specific Tissue Resident Memory T
      Cells in the Central Nervous System.
AB  - Therapies that target the PD-1/B7-H1 axis have revolutionized cancer treatment,
      yet precise knowledge of how this pathway provides benefit continues to evolve.
      Here, we report a novel role for the immune checkpoint ligand B7-H1 in the
      accumulation of tissue-resident memory CD8+ T-cells (TRM). After intracranial
      infection, Theiler's murine encephalomyelitis virus (TMEV) generates TRM that are
      maintained in the central nervous system (CNS) tissues of B7-H1WT animals.
      Although no differences in acute T-cell responses between B7-H1WT and B7-H1KO are
      observed, at long-term periods post-infection the maintenance of CD8+ TRM is
      diminished in B7-H1KO animals. This is accompanied by redistribution of the
      resident CD8+ population from primarily CD103+ TRM to a diminished population of
      TRM and a preponderance of non-specified PD-1+ CD103- CD8+ T-cells. T-cell
      transfer studies demonstrate that host B7-H1 is necessary for maintaining TRM and
      limiting accumulation of PD-1+ CD103- CD8+ T-cells. The lack of host B7-H1
      results in compromised control of a heterologous virus re-challenge demonstrating
      a functional defect in TRM mediated virus control. This study reveals a new role
      for B7-H1 in TRM and pro-inflammatory PD-1+ CD103- CD8+ T-cell accumulation in
      the CNS and gives insight for using B7-H1/PD-1 blockade in modulating long-term T
      cell protection.

PMID- 29170672
TI  - Triterpene Structural Diversification by Plant Cytochrome P450 Enzymes.
AB  - Cytochrome P450 monooxygenases (P450s) represent the largest enzyme family of the
      plant metabolism. Plants typically devote about 1% of the protein-coding genes
      for the P450s to execute primary metabolism and also to perform species-specific
      specialized functions including metabolism of the triterpenes, isoprene-derived
      30-carbon compounds. Triterpenes constitute a large and structurally diverse
      class of natural products with various industrial and pharmaceutical
      applications. P450-catalyzed structural modification is crucial for the
      diversification and functionalization of the triterpene scaffolds. In recent
      times, a remarkable progress has been made in understanding the function of the
      P450s in plant triterpene metabolism. So far, ~80 P450s are assigned biochemical
      functions related to the plant triterpene metabolism. The members of the
      subfamilies CYP51G, CYP85A, CYP90B-D, CYP710A, CYP724B, and CYP734A are generally
      conserved across the plant kingdom to take part in plant primary metabolism
      related to the biosynthesis of essential sterols and steroid hormones. However,
      the members of the subfamilies CYP51H, CYP71A,D, CYP72A, CYP81Q, CYP87D,
      CYP88D,L, CYP93E, CYP705A, CYP708A, and CYP716A,C,E,S,U,Y are required for the
      metabolism of the specialized triterpenes that might perform species-specific
      functions including chemical defense toward specialized pathogens. Moreover, a
      recent advancement in high-throughput sequencing of the transcriptomes and
      genomes has resulted in identification of a large number of candidate P450s from
      diverse plant species. Assigning biochemical functions to these P450s will be of
      interest to extend our knowledge on triterpene metabolism in diverse plant
      species and also for the sustainable production of valuable phytochemicals.

PMID- 29170674
TI  - A Pectin Methylesterase ZmPme3 Is Expressed in Gametophyte factor1-s (Ga1-s)
      Silks and Maps to that Locus in Maize (Zea mays L.).
AB  - The ga1 locus of maize confers unilateral cross incompatibility, preventing cross
      pollination between females carrying the incompatible Ga1-s allele and males not
      carrying a corresponding compatible allele. To characterize this system at the
      molecular level, we carried out a transcript profiling experiment in which silks
      from near isogenic lines carrying the Ga1-s and ga1 alleles were compared. While
      several differentially expressed genes were identified, only one mapped to the
      known location of ga1. This gene is a pectin methylesterase (PME), which we
      designated as ZmPme3, and is present and expressed only in Ga1-s genotypes. While
      a functional ZmPME3 is not present in the ga1 genotypes examined, a pectin
      methylesterase gene cluster is found in ga1 genotypes. The gene cluster in W22
      contains 58 tandem full-length or partial PME pseudo genes. These data combined
      with a wealth of previously published data on the involvement of PMEs in pollen
      tube growth suggest a role for cell wall modification enzymes in the pollen
      exclusion component of Ga1-s gametophytic incompatibility. Consistent with this
      role, a third allele which lacks the female function of Ga1-s, Ga1-m, has a
      mutationally inactivated version of ZmPme3.

PMID- 29170673
TI  - Mutant Transcriptome Sequencing Provides Insights into Pod Development in Peanut
      (Arachis hypogaea L.).
AB  - Pod size is the major yield component and a key target trait that is selected for
      in peanut breeding. However, although numerous quantitative trait loci (QTLs) for
      peanut pod size have been described, the molecular mechanisms underlying the
      development of this characteristic remain elusive. A peanut mutant with a
      narrower pod was developed in this study using ethyl methanesulfonate (EMS)
      mutagenesis and designated as the "pod width" mutant line (pw). The fresh pod
      weight of pw was only about 40% of that seen in the wild-type (WT) Zhonghua16,
      while the hull and seed filling of the mutant both also developed at earlier
      stages. Pods from both pw and WT lines were sampled 20, 40, and 60 days after
      flowering (DAF) and used for RNA-Seq analysis; the results revealed highly
      differentially expressed lignin metabolic pathway genes at all three stages, but
      especially at DAF 20 and DAF 40. At the same time, expression of genes related to
      auxin signal transduction was found to be significantly repressed during the pw
      early pod developmental stage. A genome-wide comparative analysis of expression
      profiles revealed 260 differentially expressed genes (DEGs) across all three
      stages, and two candidate genes, c26901_g1 (CAD) and c37339_g1 (ACS), responsible
      for pod width were identified by integrating expression patterns and function
      annotation of the common DEGs within the three stages. Taken together, the
      information provided in this study illuminates the processes underlying peanut
      pod development, and will facilitate further identification of causal genes and
      the development of improved peanut varieties with higher yields.

PMID- 29170676
TI  - Plasticity in Meristem Allocation as an Adaptive Strategy of a Desert Shrub under
      Contrasting Environments.
AB  - The pattern of resource allocation to reproduction vs. vegetative growth is a
      core component of a plant's life-history strategy. Plants can modify their
      biomass allocation patterns to adapt to contrasting environments. Meristems can
      have alternative fates to commit to vegetative growth, reproduction, or remaining
      inactive (dormant or senescent/dead). However, knowledge about whether meristem
      fates can interpret adaptive changes in biomass allocation remains largely
      unknown. We measured aboveground plant biomass (a proxy of plant size) and
      meristem number of a dominant shrub Artemisia ordosica in three populations
      occupying different habitats in the Mu Us Desert of northern China. Size
      dependent biomass allocation and meristem allocation among habitats were
      compared. The size-dependent biomass allocation and meristem allocation of A.
      ordosica strongly varied across habitats. There were significant positive linear
      relationships between meristem allocation and biomass allocation in all habitats,
      indicating that meristem allocation is an indicator of the estimated resource
      allocation to reproductive and vegetative organs in this species. Plasticity in
      meristem allocation was more likely caused by larger individuals having less
      active meristems due to environmental stress. Vegetative meristems (VM) were
      likely more vulnerable to environmental limitation than reproductive ones,
      resulting in the ratio of resource investment between vegetative and reproductive
      functions exhibiting plasticity in different habitats. A. ordosica invested a
      higher fraction of its resource to reproduction in the adverse habitat, while
      more resource to vegetative growth in the favorable habitat. A. ordosica adopts
      different resource allocation patterns to adapt to contrasting habitat conditions
      through altering its meristem fates. Our results suggest that the arid-adapted
      shrub A. ordosica deactivates more VM than reproductive ones to hedge against
      environmental stress, representing an important adaptive strategy. This
      information contributes to understand the life-history strategies of long-lived
      plants under stressful environments.

PMID- 29170675
TI  - The Terpene Synthase Gene Family of Carrot (Daucus carota L.): Identification of
      QTLs and Candidate Genes Associated with Terpenoid Volatile Compounds.
AB  - Terpenes are an important group of secondary metabolites in carrots influencing
      taste and flavor, and some of them might also play a role as bioactive substances
      with an impact on human physiology and health. Understanding the genetic and
      molecular basis of terpene synthases (TPS) involved in the biosynthesis of
      volatile terpenoids will provide insights for improving breeding strategies aimed
      at quality traits and for developing specific carrot chemotypes possibly useful
      for pharmaceutical applications. Hence, a combination of terpene metabolite
      profiling, genotyping-by-sequencing (GBS), and genome-wide association study
      (GWAS) was used in this work to get insights into the genetic control of terpene
      biosynthesis in carrots and to identify several TPS candidate genes that might be
      involved in the production of specific monoterpenes. In a panel of 85 carrot
      cultivars and accessions, metabolite profiling was used to identify 31 terpenoid
      volatile organic compounds (VOCs) in carrot leaves and roots, and a GBS approach
      was used to provide dense genome-wide marker coverage (>168,000 SNPs). Based on
      this data, a total of 30 quantitative trait loci (QTLs) was identified for 15
      terpenoid volatiles. Most QTLs were detected for the monoterpene compounds
      ocimene, sabinene, beta-pinene, borneol and bornyl acetate. We identified four
      genomic regions on three different carrot chromosomes by GWAS which are both
      associated with high significance (LOD >= 5.91) to distinct monoterpenes and to
      TPS candidate genes, which have been identified by homology-based gene prediction
      utilizing RNA-seq data. In total, 65 TPS candidate gene models in carrot were
      identified and assigned to known plant TPS subfamilies with the exception of TPS
      d and TPS-h. TPS-b was identified as largest subfamily with 32 TPS candidate
      genes.

PMID- 29170678
TI  - High-Resolution and Non-destructive Evaluation of the Spatial Distribution of
      Nitrate and Its Dynamics in Spinach (Spinacia oleracea L.) Leaves by Near
      Infrared Hyperspectral Imaging.
AB  - Nitrate is an important component of the nitrogen cycle and is therefore present
      in all plants. However, excessive nitrogen fertilization results in a high
      nitrate content in vegetables, which is unhealthy for humans. Understanding the
      spatial distribution of nitrate in leaves is beneficial for improving nitrogen
      assimilation efficiency and reducing its content in vegetables. In this study,
      near-infrared (NIR) hyperspectral imaging was used for the non-destructive and
      effective evaluation of nitrate content in spinach (Spinacia oleracea L.) leaves.
      Leaf samples with different nitrate contents were collected under various
      fertilization conditions, and reference data were obtained using reflectometer
      apparatus RQflex 10. Partial least squares regression analysis revealed that
      there was a high correlation between the reference data and NIR spectra (r2 =
      0.74, root mean squared error of cross-validation = 710.16 mg/kg). Furthermore,
      the nitrate content in spinach leaves was successfully mapped at a high spatial
      resolution, clearly displaying its distribution in the petiole, vein, and blade.
      Finally, the mapping results demonstrated dynamic changes in the nitrate content
      in intact leaf samples under different storage conditions, showing the value of
      this non-destructive tool for future analyses of the nitrate content in
      vegetables.

PMID- 29170677
TI  - DWARF14, A Receptor Covalently Linked with the Active Form of Strigolactones,
      Undergoes Strigolactone-Dependent Degradation in Rice.
AB  - Strigolactones (SLs) are the latest confirmed phytohormones that regulate shoot
      branching by inhibiting bud outgrowth in higher plants. Perception of SLs depends
      on a novel mechanism employing an enzyme-receptor DWARF14 (D14) that hydrolyzes
      SLs and becomes covalently modified. This stimulates the interaction between D14
      and D3, leading to the ubiquitination and degradation of the transcriptional
      repressor protein D53. However, the regulation of SL perception in rice remains
      elusive. In this study, we provide evidences that D14 is ubiquitinated after SL
      treatment and degraded through the 26S proteasome system. The Lys280 site of the
      D14 amino acid sequence was important for SL-induced D14 degradation, but did not
      change the subcellular localization of D14 nor disturbed the interaction between
      D14 and D3, nor D53 degradation. Biochemical and genetic analysis indicated that
      the key amino acids in the catalytic center of D14 were essential for D14
      degradation. We further showed that D14 degradation is dependent on D3 and is
      tightly correlated with protein levels of D53. These findings revealed that D14
      degradation takes place following D53 degradation and functions as an important
      feedback regulation mechanism of SL perception in rice.

PMID- 29170679
TI  - Frontiers in Toxicogenomics in the Twenty-First Century-the Grand Challenge: To
      Understand How the Genome and Epigenome Interact with the Toxic Environment at
      the Single-Cell, Whole-Organism, and Multi-Generational Level.

PMID- 29170680
TI  - Family structure, maternal employment, and change in children's externalizing
      problem behaviour: Differences by age and self-regulation.
AB  - This study used a latent difference score growth model to investigate how changes
      in family structure (biological father and stepfather residence) and maternal
      employment are associated with American children's externalizing problem
      behaviors (EPB) from ages 4 to 10 and whether these associations vary by
      children's level of self-regulation. For all 4 year old children, living with a
      biological father at age 4 was associated with reductions in EPB at ages 4-6 and
      later years, with no variation by child self-regulation. Living with a stepfather
      at age 4 was associated with higher levels of EPB at age 4; however, for less
      regulated children, stepfather residence at ages 4 and 8 was associated with
      reductions in EPB between ages 4-6 and from 8-10, respectively. Greater
      employment hours were associated with increased EPB in the next two years for
      less-regulated children of all ages; however, except for the age 4-6 transition,
      there was a lagged association that reduced behavior problems after two years and
      outweighed short-term increases.

PMID- 29170681
TI  - Education, substance use, and HIV risk among orphaned adolescents in Eastern
      Zimbabwe.
AB  - There is a growing interest in education as a means to reduce HIV infection in
      vulnerable children in sub-Saharan Africa; however, the mechanisms by which
      education reduces HIV infection remain uncertain. Substance use has been
      associated with high-risk sexual behaviour and could lie on the causal pathway
      between education and HIV risk. Therefore, we used multivariable regression to
      measure associations between: (i) orphanhood and substance use (alcohol,
      recreational drugs, and smoking), (ii) substance use and sexual risk behaviours,
      and (iii) school enrolment and substance use, in adolescents aged 15-19 years, in
      Eastern Zimbabwe. We found substance use to be low overall (6.4%, 3.2%, and 0.9%
      of males reported alcohol, drug, and cigarette use; <1% of females reported any
      substance use), but was more common in male maternal and double orphans than non
      orphans. Substance use was positively associated with early sexual debut, number
      of sexual partners, and engaging in transactional sex, while school enrolment was
      associated with lower substance use in males. We conclude that education may
      reduce sexual risk behaviours and HIV infection rates among male adolescents in
      sub-Saharan Africa, in part, by reducing substance abuse.

PMID- 29170682
TI  - Adaptive Skill Trajectories in Infants with Fragile X Syndrome Contrasted to
      Typical Controls and Infants at High Risk for Autism.
AB  - Background: Adaptive behaviors are essential for optimal outcomes and
      independence in individuals with developmental disabilities. This study examined
      longitudinal trajectories of adaptive behavior in infants with fragile X syndrome
      (FXS), compared to typical development (TD) and infant siblings of children
      diagnosed with autism (ASIBs). Method: Participants included 76 male infants (FXS
      =25, ASIBs=27, TD = 24) assessed up to 4 times between 6 and 24 months of age for
      a total of 215 assessments of adaptive behavior. A sample of 12 females with FXS
      was included for a comparative sex analysis. Results: Results indicate that
      infant males with FXS displayed lower initial adaptive behavior across all
      domains that emerged by 9 months-of-age with slower growth rates than both
      comparison groups. A flat profile across the domains at 24 months was evident.
      Increased severity of autism symptoms was related to reduced adaptive skills at
      24 months-of-age. Females with FXS displayed higher scores than males on the
      Socialization and Motor domains and equivalent scores on the Communication and
      Daily Living domains at 9 months-of-age with different rates of growth across
      domains. Conclusions: This is the first study to provide evidence of etiological
      specificity in adaptive behavior profiles during infancy across two populations
      at high risk for ASD. These findings support targeted adaptive behavior
      interventions in young children with FXS beginning as early at 9 months of age to
      reduce identified deficits and the cascading impacts of these early impairments.

PMID- 29170683
TI  - A Systematic Review of Research into the Impact of Loose Parts Play on Children's
      Cognitive, Social and Emotional Development.
AB  - Loose parts play (LPP) interventions introduce moveable materials and equipment
      to children's play spaces to facilitate unstructured, child-led play. Meta
      analysis of previous school-based research has shown significant benefits of LPP
      for physical activity. In the current paper, we review the scope and quality of
      the quantitative evidence relating to cognitive, social and emotional outcomes.
      We conducted a systematic search of the literature on LPP interventions for
      primary school-aged children which used quantitative outcome indicators for
      cognitive, social and/or emotional development. Studies were screened for
      inclusion by two independent researchers and reviewed for content, relevant
      outcomes and quality indicators. Five studies met the review inclusion criteria.
      Two studies used a randomised controlled trial design, two studies used quasi
      experimental design, and one used an observational design. Outcomes measured
      focused mainly on social development. With the exception of enjoyment, school
      satisfaction and self-esteem, emotional outcomes were almost entirely absent. No
      measures of cognitive or academic outcomes were found. For the studies using
      control groups, few differences between groups were reported, although one study
      found increased happiness at school and increased odds of reporting being
      pushed/shoved at playtime associated with intervention. Null results were found
      for peer acceptance, relational bullying, social competence, social skills, peer
      group size and psychosocial quality of life. In the non-controlled study, there
      were observed increases in co-operative play. There is insufficient high-quality,
      quantitative, empirical evidence available to determine whether or not LPP
      interventions have an impact on children's cognitive, social and emotional
      development. We conclude our review with some recommendations which we hope will
      assist future research in this promising field.

PMID- 29170684
TI  - From basics to clinic: Cancer Nanotechnology.

PMID- 29170685
TI  - Connection Between Thermodynamics and Dynamics of Simple Fluids in Pores: Impact
      of Fluid-Fluid Interaction Range and Fluid-Solid Interaction Strength.
AB  - Using molecular simulations, we investigate how the range of fluid-fluid
      (adsorbate-adsorbate) interactions and the strength of fluid-solid (adsorbate
      adsorbent) interactions impact the strong connection between distinct adsorptive
      regimes and distinct self-diffusivity regimes reported in [Krekelberg, W. P.;
      Siderius, D. W.; Shen, V. K.; Truskett, T. M.; Errington, J. R. Langmuir2013, 29,
      14527-14535]. Although increasing the fluid-fluid interaction range changes both
      the thermodynamics and the dynamic properties of adsorbed fluids, the previously
      reported connection between adsorptive filling regimes and self-diffusivity
      regimes remains. Increasing the fluid-fluid interaction range leads to enhanced
      layering and decreased self-diffusivity in the multilayer-formation regime but
      has little effect on the properties within film-formation and pore-filling
      regimes. We also find that weakly attractive adsorbents, which do not display
      distinct multilayer formation, are hard-sphere-like at super- and subcritical
      temperatures. In this case, the self-diffusivity of the confined and bulk fluid
      has a nearly identical scaling-relationship with effective density.

PMID- 29170686
TI  - Charge-Transfer Analysis of 2p3d Resonant Inelastic X-ray Scattering of Cobalt
      Sulfide and Halides.
AB  - We show that with 2p3d resonant inelastic X-ray scattering (RIXS) we can
      accurately determine the charge-transfer parameters of CoF2, CoCl2, CoBr2, and
      CoS. The 160 meV resolution RIXS results are compared with charge-transfer
      multiplet calculations. The improved resolution and the direct observation of the
      crystal field and charge-transfer excitations allow the determination of more
      accurate parameters than could be derived from X-ray absorption and X-ray
      photoemission, both limited in resolution by their lifetime broadening. We derive
      the crystal field and charge-transfer parameters of the Co2+ ions, which provides
      the nature of the ground state of the Co2+ ions with respect to symmetry and
      hybridization. In addition, the increased spectral resolution allows the more
      accurate determination of the atomic Slater integrals. The results show that the
      crystal field energy decreases with increasing ligand covalency. The L2 edge RIXS
      spectra show that the intensity of the (Coster-Kronig induced) nonresonant X-ray
      emission is a measure of ligand covalency.

PMID- 29170687
TI  - Methane Adsorption in Zr-Based MOFs: Comparison and Critical Evaluation of Force
      Fields.
AB  - The search for nanoporous materials that are highly performing for gas storage
      and separation is one of the contemporary challenges in material design. The
      computational tools to aid these experimental efforts are widely available, and
      adsorption isotherms are routinely computed for huge sets of (hypothetical)
      frameworks. Clearly the computational results depend on the interactions between
      the adsorbed species and the adsorbent, which are commonly described using force
      fields. In this paper, an extensive comparison and in-depth investigation of
      several force fields from literature is reported for the case of methane
      adsorption in the Zr-based Metal-Organic Frameworks UiO-66, UiO-67, DUT-52, NU
      1000, and MOF-808. Significant quantitative differences in the computed uptake
      are observed when comparing different force fields, but most qualitative features
      are common which suggests some predictive power of the simulations when it comes
      to these properties. More insight into the host-guest interactions is obtained by
      benchmarking the force fields with an extensive number of ab initio computed
      single molecule interaction energies. This analysis at the molecular level
      reveals that especially ab initio derived force fields perform well in
      reproducing the ab initio interaction energies. Finally, the high sensitivity of
      uptake predictions on the underlying potential energy surface is explored.

PMID- 29170688
TI  - Emergence of Nonlinear Optical Activity by Incorporation of a Linker Carrying the
      p-Nitroaniline Motif in MIL-53 Frameworks.
AB  - p-Nitroaniline presents the typical motif of a second-order nonlinear optically
      (NLO) active molecule. However, because of its crystallization in an antiparallel
      and hence centrosymmetric structure, the NLO activity is lost. In this
      contribution, the p-nitroaniline motif was built successfully into the MIL-53
      metal-organic framework. More precisely, MIL-53 was synthesized with 2-amino-5
      nitroterephthalate as organic linker, with Al3+, Ga3+, or In3+ as inorganic
      cation. The Al and Ga structures are polar, as confirmed by second-harmonic
      generation microscopy, yielding stable NLO materials. Indeed, they contain a 22
      36% surplus of the dipolar 2-amino-5-nitro-terephthalate oriented in a parallel
      fashion. The indium compound was shown to be less crystalline and
      centrosymmetric. Ab initio modeling of the second-order NLO response shows that
      the Al and Ga materials show a response comparable to typical inorganic
      commercial NLO materials such as KDP. As a hybrid material, capable of low
      temperature synthesis and processing and the ultrafast NLO responses associated
      with organic materials, this material can potentially provide an interesting
      venue for applications with respect to traditional inorganic NLO materials.

PMID- 29170689
TI  - Perception of Community Tolerance and Prevalence of Depression among Transgender
      Persons.
AB  - Purpose: The goal of the study was to examine the association between depression
      and perceived community tolerance after controlling for various demographic and
      personal characteristics, treatment receipt, and past experiences with abuse or
      discrimination. Methods: An on-line survey assessed depressive symptoms among
      transgender and gender non-conforming individuals. Depression was assessed using
      the 7-item Beck Depression Inventory for Primary Care (BDI-PC) and the 10-item
      Center for Epidemiologic Studies Depression (CESD-10) scale. Results: The
      prevalence ratios (95% confidence intervals) comparing depression in persons who
      did and did not perceive their area as tolerant were 0.33 (0.20-0.54) for BD-PC
      and 0.66 (0.49-0.89) for CESD-10. Other factors associated with depression were
      experience with abuse or discrimination, lower education, and unfulfilled desire
      to receive hormonal therapy. Conclusion: Depression was common in this sample of
      transgender and gender non-conforming individuals and was strongly and
      consistently associated with participants' perceptions of community tolerance,
      even after adjusting for possible confounding. The association between desire to
      receive hormonal therapy and depression is a finding that warrants further
      exploration. Future research should also assess depression and changes in
      perception of community tolerance in transgender individuals before and after
      initiation of gender confirmation treatment.

PMID- 29170690
TI  - Correlation between the Functional Movement Screen and Hip Mobility in NCAA
      Division II Athletes.
AB  - The Functional Movement Screen (FMS) is a series of seven exercises designed to
      assess athletes prior to competitive training to determine dysfunctional movement
      patterns. The exercises include the deep squat (DS), hurdle step (HS), inline
      lunge (IL), shoulder mobility (SM), active straight leg raise (ASL), pushup (PU),
      and rotary stability (RS), all of which comprise the composite score (FMS CS).
      The purpose of this study was to determine correlations between the FMS screens
      and hip mobility. The specific hip range-of-motion exercises used were bilateral
      internal/external rotation (IRR, IRL ERL, ERR), and flexion/extension (FL, FR,
      ER, EL). Participants of both genders (32 males, 13 females) were solicited from
      four sports (baseball, softball, and men's and women's cross-country). The most
      significant/intriguing correlations were between FMS HS/FL, FMS ILL/R, FMS PU/FL,
      FMS ALL and IRR/L and ERR/L and FMS SM/ER. All correlations produced were weak to
      moderate at the .05 level of significance. These results demonstrate that hip
      range-of-motion plays a minor role in FMS score. Future studies should utilize a
      larger sample size, including more females, as well as analyze range-of-motion
      across multiple joints.

PMID- 29170691
TI  - Does Time Heal all Wounds? A Case Study on Rival Perceptions Before and After
      Conference Realignment.
AB  - The current longitudinal case study investigated how conference realignment and
      beginning new annual competitions impacted fan rival perceptions for fans of the
      Texas A&M Aggies, Missouri Tigers, and Texas Christian University Horned Frogs.
      In particular, fan rival perceptions before and after conference realignment were
      compared to determine if significant differences were present. Findings indicate
      that history plays an important role in rivalry as fans of teams sharing
      longstanding rivalries with schools in their previous conference (i.e., Texas
      A&M/Texas and Missouri/Kansas) did not differ in their rival perceptions before
      or after conference realignment. On the other hand, rival perceptions of TCU fans
      significantly differed in their perceptions of Boise State (previous rival) and
      Baylor (current rival) before and after conference realignment. Implications for
      sport managers are discussed.

PMID- 29170692
TI  - "I will change the world": The Intersection of Social Change and Male College
      Athletes' Leadership Perspectives.
AB  - Historically, men have been characterized as task-oriented leaders who are
      motivated by desires for autonomy, wealth, and power (17, 33). However, these
      "masculine" views of leadership might not accurately capture the leadership
      motivations of Millennial males as the views were developed in previous
      generations (4). Given the commitment of many Millennials towards socially
      responsible attitudes and behaviors (18, 25), we utilized a qualitative research
      design to examine the influence of social change on the leadership motivations of
      Millennial male intercollegiate athletes. In doing so, we found participants were
      motivated to lead in order to affect social change within their communities and
      within society. Our findings indicate a new perspective, one which includes a
      commitment to social change, is potentially needed when discussing "masculine"
      views of leadership.

PMID- 29170693
TI  - From Crisis to De-escalation: An Examination of Politics in a U.S. High School
      Steroid Testing Program.
AB  - Preventing the use of performance enhancing drugs in sport has long been a
      concern for policymakers. In the United States, amidst national attention the
      state of Texas constructed the country's largest steroid testing program for high
      school athletes. However, resource allocation steadily declined until the program
      was defunded in 2015. Using escalation of commitment theory as a framework, this
      conceptual paper examines the critical, but less studied, role of politics and de
      escalation behavior that directed this distinct sport situation. By combining
      policy and media documents with the academic literature, this paper allows for a
      greater understanding of how the steroid testing program was formulated and
      implemented, which may influence how policymakers address steroids among amateur
      athletes in the future. This paper also offers new opportunities for future
      research by highlighting a new sport context in which escalation of commitment
      theory applies and specifically noting the significant role politics can play in
      escalation or de-escalation decision making.

PMID- 29170694
TI  - The Relationship Between Athletic Identity and Academic Major Chosen by Student
      Athletes.
AB  - This study examines the correlation between athletic identity and academic major
      selection among intercollegiate student-athletes. A thorough review of literature
      focusing on academic clustering, athletic identity, and academic development
      leads to the development of two hypotheses - 1) student-athletes with stronger
      athletic identity will have a declared major of decreased academic rigor; and 2)
      student-athletes with stronger athletic identity will be more likely to be
      undecided on their major. Data were collected through a survey administered to
      Division I, II, and III student-athletes recording academic major and their
      Athletic Identity Measurement Scale (AIMS). After analyzing the student
      responses, Hypothesis I is supported, while Hypothesis II is met with some
      limitation that leads to a lack of statistical significance. Overall, this study
      sheds light on a connection between academic choice and athletic identity.

PMID- 29170695
TI  - Students' Perceptions of an Applied Research Experience in an Undergraduate
      Exercise Science Course.
AB  - Applied research experiences can provide numerous benefits to undergraduate
      students, however few studies have assessed the perceptions of Exercise Science
      (EXS) students to an applied research experience. The purpose of this study was
      two-fold: 1) to describe the rationale and implementation of an applied research
      experience into an EXS curriculum and 2) to evaluate EXS undergraduate students'
      perceptions of an applied research experience. An EXS measurement course was
      chosen for implementation of an applied research experience. The applied research
      experience required groups of students to design, implement, and evaluate a
      student-led research project. Fourteen questions were constructed, tailored to
      EXS undergraduate students, to assess students' perceptions of the experience.
      Qualitative analysis was used for all applicable data, with repeated trends
      noted; quantitative data were collapsed to determine frequencies. There was an
      overall positive student perception of the experience and 85.7% of students
      agreed an applied research experience should be continued. 84.7% of students
      perceived the experience as educationally enriching, while 92.8% reported the
      experience was academically challenging. This experience allowed students to
      develop comprehensive solutions to problems that arose throughout the semester;
      while facilitating communication, collaboration, and problem solving. Students
      believed research experiences were beneficial, but could be time consuming when
      paired with other responsibilities. Results suggest an applied research
      experience has the potential to help further the development of EXS undergraduate
      students. Understanding student perceptions of an applied research experience may
      prove useful to faculty interested in engaging students in the research process.

PMID- 29170696
TI  - Speed- and Circuit-Based High-Intensity Interval Training on Recovery Oxygen
      Consumption.
AB  - Due to the current obesity epidemic in the United States, there is growing
      interest in efficient, effective ways to increase energy expenditure and weight
      loss. Research has shown that high-intensity exercise elicits a higher Excess
      Post-Exercise Oxygen Consumption (EPOC) throughout the day compared to steady
      state exercise. Currently, there is no single research study that examines the
      differences in Recovery Oxygen Consumption (ROC) resulting from high-intensity
      interval training (HIIT) modalities. The purpose of this study is to review the
      impact of circuit training (CT) and speed interval training (SIT), on ROC in both
      regular exercising and sedentary populations. A total of 26 participants were
      recruited from the UW-Eau Claire campus and divided into regularly exercising and
      sedentary groups, according to self-reported exercise participation status.
      Oxygen consumption was measured during and after two HIIT sessions and was used
      to estimate caloric expenditure. There was no significant difference in caloric
      expenditure during and after exercise among individuals who regularly exercise
      and individuals who are sedentary. There was also no significant difference in
      ROC between regular exercisers and sedentary or between SIT and CT. However,
      there was a significantly higher caloric expenditure in SIT vs. CT regardless of
      exercise status. It is recommended that individuals engage in SIT vs. CT when the
      goal is to maximize overall caloric expenditure. With respect to ROC, individuals
      can choose either modalities of HIIT to achieve similar effects on increased
      oxygen consumption post-exercise.

PMID- 29170697
TI  - Effects of Flexibility and Balance on Driving Distance and Club Head Speed in
      Collegiate Golfers.
AB  - Good balance, flexibility, and strength are all required to maintain a steady
      stance during the kinematic chain to produce successful golf shots. When the body
      can produce more power, more club head speed is generated. This formation of
      power translates into greater distance and accuracy. Athletes today are seeking
      exercise programs to enhance these qualities of their golf swing. The purpose of
      this study is to investigate the correlations between flexibility and balance
      with club head speed and driving distance in the golf swing of male and female
      collegiate golfers. Five male and five female collegiate golfers participated in
      the study. They completed multiple range of motion tests, the Balance Error
      System Test, and multiple flexibility tests. Subjects then participated in a
      short hitting session. Ten shots were hit with the subject's own driver. The
      Optishot simulator measured distance and club head speed generated. There was a
      significant negative correlation between the BESS test score and average distance
      for male subjects (r=-0.850, p=0.034). There were also a few trends between the
      balance, flexibility, and club head speed findings of both male and female
      subjects. This data shows there is a significant relationship between better
      balance and driving the ball farther. Other trends show better balance and
      flexibility will result in greater driving distance and club head speed. Balance
      and flexibility exercises should be incorporated into a golfer's practice or
      workout regiment.

PMID- 29170698
TI  - Effects of the Boy Scouts of America Personal Fitness Merit Badge on Cardio
      Metabolic Risk, Health Related Fitness and Physical Activity in Adolescent Boys.
AB  - A growing number of adolescents are more sedentary and have fewer formal
      opportunities to participate in physical activity. With the mounting evidence
      that sedentary time has a negative impact on cardiometabolic profiles, health
      related fitness and physical activity, there is a pressing need to find an
      affordable adolescent physical activity intervention. One possible intervention
      that has been overlooked in the past is Boy Scouts of America. There are nearly
      900,000 adolescent boys who participate in Boy Scouts in the United States. The
      purpose of this research study was to evaluate the effect of the Personal Fitness
      merit badge system on physical activity, health-related fitness, and cardio
      metabolic blood profiles in Boy Scouts 11-17 years of age. Participants were
      fourteen (N = 14) Boy Scouts from the Great Salt Lake Council of the Boy Scouts
      of America who earned their Personal Fitness merit badge. Classes were held in
      the Spring of 2016 where boys received the information needed to obtain the merit
      badge and data were collected. Results from the related-samples Wilcoxon signed
      rank test showed that the median of differences between VO2 peak pre-test and
      post-test scores were statistically significant (p = 0.004). However, it also
      showed that the differences between the Pre-MetS (metabolic syndrome) and Post
      MetS scores (p = 0.917), average steps taken per day (p = 0.317), and BMI (p =
      0.419) were not statistically significant. In conclusion, the merit badge program
      had a positive impact on cardiovascular endurance, suggesting this program has
      potential to improve cardiovascular fitness and should be considered for boys
      participating in Boy Scouts.

PMID- 29170700
TI  - The Effect of a Single Bout of Surfing on Exercise-Induced Affect.
AB  - Exercise-induced affect (EIA) has been well documented and is often composed of
      positive affect, negative affect, tranquility, and fatigue. Research on EIA has
      focused on mainstream sports such as running, walking, or cycling; however, no
      research has evaluated the influence of action sports participation in activities
      such surfing on EIA. The current study examined the effect of a single 30-min
      surfing bout on EIA in 107 adult volunteers. An additional purpose was if change
      in affect was similar based on surfing history, surfing frequency, and surfing
      skill level. To assess EIA, each participant completed the Physical Activity
      Affect Scale (PAAS) prior to and immediately following the 30-min surf session.
      Dependent t-tests were used to examine differences between pre- and post-test
      EIA. For the secondary purpose, a change score (PAAS posttest-PAAS pretest) was
      computed for each subscale. One-way ANOVAs were performed to determine
      differences among comparisons of surfing history, surfing frequency, and surfing
      skill level, and the change score for each of the 4 subscales. EIA was
      significantly altered by surfing, with significant improvements in positive
      affect and tranquility, and significant reductions in negative affect and
      fatigue. There were no significant differences among surfing history, surfing
      frequency, and surfing skill level, and positive affect, negative affect or
      tranquility. However, there were significant differences between fatigue and
      surfing history, surfing frequency, and surfing skill level. The results indicate
      that a single 30-min surfing bout may provide positive benefits for the
      participant. Implications for future surfing research and EIA are discussed.

PMID- 29170699
TI  - Validity of Arm-to-Arm BIA Devices Compared to DXA for Estimating % Fat in
      College Men and Women.
AB  - Bioelectric impedance analysis (BIA) devices are commonly used to estimate
      percent body fat (%fat), although validation of their accuracy varies widely. The
      purpose of this study was to assess the validity of four commonly used BIA
      devices compared to dual-energy X-ray absorptiometry (DXA). College-aged men (n =
      29, age = 19.7 +/- 1.2 y, weight = 76.9 +/- 12.5 kg) and women (n = 31, age =
      20.5 +/- 0.8 y, weight = 61.5 +/- 9.2 kg) were evaluated for %fat using four
      single-frequency (50 mHz) BIA devices and DXA. A gender * device repeated
      measures ANOVA indicated some less expensive BIA devices produced %fat values
      that were not significantly different from DXA. A thumb-to-thumb BIA device
      produced the closest values in men (21.9 +/- 6.6%) and women (32.1 +/- 5.3%)
      compared to DXA (20.6 +/- 6.1% and 30.3 +/- 5.4%, respectively). The two more
      expensive BIA devices significantly underestimated in men (14.7 +/- 5.8% and 17.0
      +/- 5.6%) and women (23.3 +/- 4.2% and 23.3 +/- 4.2%) compared to DXA. Interclass
      correlation coefficients with DXA were higher for the more expensive devices in
      men (ICC = 0.899 and 0.958) than the less expensive devices (ICC = 0.681 and
      0.730). In women, all BIA devices showed moderate correlations with DXA (ICC =
      0.537 to 0.658). Despite the convenience of simple BIA devices, their use in
      estimating body composition in young men and women might be questionable due to
      large variations in the differences between DXA and each device in this study.

PMID- 29170701
TI  - A Pre-Exercise Dose of Muscle Sentry(r) has no Effect on Performing Repeated Leg
      Press Sets to Failure.
AB  - This study compared the number of bilateral leg presses done at 150% of body mass
      while on either Muscle Sentry(r) (MS) or placebo (PL). Participants (16 women, 14
      men, college students 19-26 years) performed 2 sets of leg press to failure using
      150% of their body mass with 5 min rest separating the 2 sets. Each exercise was
      performed twice (1* MS, 1* PL) at the same time of day with 48 h separating each
      exercise. Both MS and PL were ingested 30 min prior to performing the exercise.
      Just prior to starting the exercise and at the end of each set, heart rate, and
      blood pressure were obtained and the rate pressure product was calculated to
      determine myocardial workload. Two-way repeated measures ANOVA for lift number
      showed no significant main effects for either MS vs. PL, or for Set1 vs. Set2 (p
      > 0.05). The interaction was also not statistically different (mean repetitions
      +/- std. dev.: MS1= 28+/-20, MS2= 26+/-18, PL1 = 30+/-24, PL2 = 29+/-20). Two-way
      repeated measures ANOVA for rate pressure product showed no significance for
      either the main effect for MS vs. PL, or supplement * pre-post interaction (p >
      0.05). The main effect for pre-lift vs. post lift was significant (p<0.001) with
      post being higher than pre. Ingestion of Muscle Sentry(r) 30 min prior to leg
      pressing 150% of body mass to failure had no effect upon either total work
      performance or myocardial workload.

PMID- 29170702
TI  - College Student Work Habits are Related to Physical Activity and Fitness.
AB  - Despite the known benefits of regular physical activity, research shows a
      significant decline in physical activity participation and an increase in
      sedentary behavior during young adulthood during the college years. Studies
      examining the relationship between academic outcomes and fitness/physical
      activity have not extensively examined this among college students. Therefore,
      the purpose of this study was to examine the relationship between fitness
      measures (cardiovascular endurance, muscular endurance, flexibility and body
      composition), physical activity, and academic outcomes in college students. This
      cross-sectional study had college students complete a one-time fitness assessment
      and survey examining their physical activity and academic factors (GPA, study
      habits, course load). Correlations examined relationships between fitness,
      physical activity and academic outcomes, t-tests compared differences for fitness
      and behavioral outcomes between groups by academic factors. The final sample
      (n=512) was 50.4% male, 78% Non-Hispanic White, and 67% upperclassmen. The
      majority (76%) of participants reported meeting current PA guidelines. Hours of
      studying and social media use were both positively associated with body fat.
      Course load was negatively associated with vigorous activity. Study time was
      negatively associated with cardiovascular endurance, positively associated with
      hip flexibility and sedentary behavior. Higher GPA was associated with a higher
      BMI and a higher credit load was associated with less vigorous physical activity.
      These findings indicated that academic outcomes and physical activity may have a
      different relationship among college students compared with younger age groups.
      This study provides insight for the development of future campus-based health
      initiatives to have a shared focus of academic outcomes and physical activity.

PMID- 29170703
TI  - Nutrient Intake of Elite Canadian and American Athletes with Spinal Cord Injury.
AB  - The nutrient needs of athletes with Spinal Cord Injury (SCI) are dependent on
      their physiological alterations and training status. Limited research is
      available regarding dietary intake of elite athletes with SCI and possible
      nutrient deficiencies. Therefore, the purpose of this study was to examine
      dietary intake of elite athletes with SCI, and determine dietary intake
      inadequacies based on the Estimated Average Requirement (EAR) comparisons.
      Additionally, the average energy and macronutrient (carbohydrate, protein, and
      fat) intake was compared based on level of injury (C level, T1-T6, T7-T12,
      Lumbar). A total of 39 athletes with a SCI completed a self-reported 24 hour diet
      recall in autumn and 27 athletes returned to complete a second data collection
      period (winter). Nutrient inadequacy was estimated by the proportion of athletes
      with mean intakes below the EAR through the Research Solutions Food Processor
      Diet Analysis Software (ESHA). Although Macronutrients for both men and women
      were within acceptable macronutrient distribution range (AMDR) recommendations,
      low EAR's for various nutrients were consistently found for both men and women.
      No significant differences were found for energy or macronutrient intake between
      groups based on level of lesion. Further research is needed to examine nutrient
      intake using other methods of dietary assessment and to determine the factors
      that may lead to nutrient insufficiency among elite athletes with SCI.

PMID- 29170704
TI  - A Pre-Exercise Dose of Melatonin Can Alter Substrate Use During Exercise.
AB  - Notwithstanding the lack of exercise research, several reviews have championed
      the use of melatonin to combat metabolic syndrome. Therefore, this study compared
      substrate utilization during a 30-minute (min) graded exercise protocol following
      the ingestion of either 6 mg melatonin (M) or a placebo (P). Participants (12
      women, 12 men) performed stages 1-5 of the Naughton graded exercise protocol (6
      min per stage). The protocol was repeated 4 times (2x M, 2x P) at the same time
      of day with one week separating each session. Expired gases were monitored, VO2
      and respiratory exchange ratio (RER) output was provided every 30s. Total,
      carbohydrate (CHO), and fat energy expenditures were obtained from the RER values
      using the formulae of Lusk. The VO2 at which CHO accounted for 50% of the total
      caloric expenditure was calculated by a VO2: RER regression line. Additionally,
      the energy derived was calculated by multiplying VO2 and the respective energy
      expenditures. Then, the total, CHO, and fat energies consumed during the 30 min
      of exercise were determined by calculating the area under the kJ/min: time curve
      using the trapezoid rule. The final data for the two similar trials were averaged
      and a paired-T test was used for statistical comparison. The average VO2 for 50%
      CHO usage was significantly lower following M (0.84 +/- 0.54 l.min-1) than after
      P (1.21 +/- 0.52 l.min-1). Also, average CHO kJ for M (627 +/- 284) was
      significantly (p < 0.004) greater than P (504 +/- 228), and accounted for a
      significantly greater contribution of total kJ consumed (M = 68% +/-15 vs. P =
      61% +/- 18). Ingestion of melatonin 30 min prior to an aerobic exercise bout
      elevates CHO use during exercise.

PMID- 29170705
TI  - Energy Cost of Active and Sedentary Music Video Games: Drum and Handheld Gaming
      vs. Walking and Sitting.
AB  - To compare energy expenditure during and after active and handheld video game
      drumming compared to walking and sitting. Ten experienced, college-aged men
      performed four protocols (one per week): no-exercise seated control (CTRL),
      virtual drumming on a handheld gaming device (HANDHELD), active drumming on drum
      pads (DRUM), and walking on a treadmill at ~30% of VO2max (WALK). Protocols were
      performed after an overnight fast, and expired air was collected continuously
      during (30min) and after (30min) exercise. DRUM and HANDHELD song lists, day of
      the week, and time of day were identical for each participant. Significant
      differences (p < 0.05) among the average rates of energy expenditure (kcal.min-1)
      during activity included WALK > DRUM > HANDHELD. No significant differences in
      the rates of energy expenditure among groups during recovery were observed. Total
      energy expenditure was significantly greater (p < 0.05) during WALK (149.5 +/-
      30.6 kcal) compared to DRUM (118.7 +/- 18.8 kcal) and HANDHELD (44.9+/-11.6
      kcal), and greater during DRUM compared to HANDHELD. Total energy expenditure was
      not significantly different between HANDHELD (44.9 +/- 11.6 kcal) and CTRL (38.2
      +/- 6.0 kcal). Active video game drumming at expert-level significantly increased
      energy expenditure compared to handheld, but it hardly met moderate-intensity
      activity standards, and energy expenditure was greatest during walking. Energy
      expenditure with handheld video game drumming was not different from no-exercise
      control. Thus, traditional aerobic exercise remains at the forefront for
      achieving the minimum amount and intensity of physical activity for health,
      individuals desiring to use video games for achieving weekly physical activity
      recommendations should choose games that require significant involvement of lower
      body musculature, and time spent playing sedentary games should be a limited part
      of an active lifestyle.

PMID- 29170706
TI  - The Effects of Resistance Training Volume on Skeletal Muscle Proteome.
AB  - Studies are conflicting to whether low volume resistance training (RT) is as
      effective as high-volume RT protocols with respect to promoting morphological and
      molecular adaptations. Thus, the aim of the present study was to compare, using a
      climbing a vertical ladder, the effects of 8 weeks, 3 times per week, resistance
      training with 4 sets (RT4), resistance training with 8 sets (RT8) and without
      resistance training control (CON) on gastrocnemius muscle proteome using liquid
      chromatography mass spectrometry (LC-MS/MS) and cross sectional area (CSA) of
      rats. Fifty-two proteins were identified by LC-MS/MS, with 39 in common between
      the three groups, two in common between RT8 and CON, one in common between RT8
      and RT4, four exclusive in the CON, one in the RT8, and four in the RT4. The RT8
      group had a reduced abundance of 12 proteins, mostly involved in muscle protein
      synthesis, carbohydrate metabolism, tricarboxylic acid cycle, anti-oxidant
      defense, and oxygen transport. Otherwise one protein involved with energy
      transduction as compared with CON group showed high abundance. There was no
      qualitative protein abundance difference between RT4 and CON groups. These
      results revealed that high volume RT induced undesirable disturbances on skeletal
      muscle proteins, while lower volume RT resulted in similar gains in skeletal
      muscle hypertrophy without impairment of proteome. The CSA was significantly
      higher in RT8 group when compared to RT4 group, which was significantly higher
      than CON group. However, no differences were found between trained groups when
      the gastrocnemius CSA were normalized by the total body weight.

PMID- 29170707
TI  - Is the Relationship Between Stride Length, Frequency, and Velocity Influenced by
      Running on a Treadmill or Overground?
AB  - The purpose of the study was to compare the relationship between stride length
      (SL), stride frequency (SF), and velocity while running on a treadmill and
      overground. Participants (n=10; 22.3+/-2.6 yrs; 1.71+/-.08 m; 71.4+/-15.5 kg)
      completed a total of 14 runs (7 treadmill, 7 overground) with each run at a
      different velocity. SL, SF, and velocity data were recorded using wearable
      technology (Garmin, Fenix2). The outdoor trials occurred first. The treadmill
      velocities were selected to match the range of velocities used overgroud. SL vs.
      velocity plots were generated for treadmill and overground data for each
      participant and fit with a 2nd order polynomial in the form of SL=Av2+Bv+C. Each
      equation coefficient (i.e., A, B, C) was averaged across participants and
      compared between treadmill and overground using paired t-tests. The A coefficient
      (v2 term) was different treadmill vs. overground (p=0.031). Neither B (p=0.136)
      nor C (p=0.260) coefficients were different treadmill vs. overground. It was
      concluded that the A coefficient (v2 term) for SL vs. velocity was larger during
      overground vs. treadmill running. This is an indication that the strategy of
      changing SL across velocities was different when on the treadmill vs. overground.
      Specifically, while running on a treadmill, SL continued to increase in a more
      linear manner than when running overground.

PMID- 29170709
TI  - Effects of Heat Exposure on Body Water Assessed using Single-Frequency
      Bioelectrical Impedance Analysis and Bioimpedance Spectroscopy.
AB  - The purpose of this study was to determine if heat exposure alters the measures
      of total body water (TBW), extracellular water (ECW), and intracellular water
      (ICW) in both single-frequency bioelectrical impedance analysis (BIA) and
      bioimpedance spectroscopy (BIS). Additionally, we sought to determine if any
      differences exist between the BIA and BIS techniques before and after brief
      exposure to heat. Body water was evaluated for twenty men (age=24+/-4 years) in a
      thermoneutral environment (22 degrees C) before (PRE) and immediately after
      (POST) 15 min of passive heating (35 degrees C) in an environmental chamber. The
      mean difference and 95% limits of agreement at PRE demonstrated that BIS yielded
      significantly higher body water values than BIA (all p<0.05; TBW=1.8kg; ECW=0.6+/
      1.3kg; ICW=1.2+/-3.7kg). However, the effect size (ES) of the mean differences at
      PRE were small and the r-values were high (r>=0.97). TBW and ICW remained
      significantly higher at POST for BIS (both p<0.05; 1.4+/-3.2kg and 1.1+/-3.7kg,
      respectively) whereas ECW was not different (p>0.05; 0.2+/-1.5kg). Additionally,
      the ES of the mean differences at POST were trivial to small and the r-values
      were high (r>=0.96). When analyzing the changes in body water before and after
      heat exposure, POST values for BIS were significantly higher than PRE (all
      p<0.001; TBW=0.6+/-0.8kg; ECW=0.4+/-0.3kg; ICW=0.3+/-0.6kg). Similarly, POST
      values for BIA were significantly higher than PRE (all p<0.001; TBW=1.0+/-0.6kg;
      ECW=0.7+/-0.4kg; ICW=0.4+/-0.4kg). BIA and BIS provide similar body water
      estimates. However, the increase in POST body water values indicate more research
      is needed before either method can be used for estimating body water after heat
      exposure.

PMID- 29170708
TI  - Repeated Plyometric Exercise Attenuates Blood Glucose in Healthy Adults.
AB  - Plyometric exercise is popular in commercial exercise programs aiming to maximize
      energy expenditure for weight loss. However, the effect of plyometric exercise on
      blood glucose is unknown. The purpose of this study was to investigate the effect
      of relatively high intensity plyometric exercise on blood glucose. Thirteen
      subjects (6 females age= 21.8 +/- 1.0 yrs.; height= 163.7 +/- 7.8 cm; mass= 60.8
      +/- 6.7 kg and 7 males age= 22.0 +/- 2.6 yrs.; height= 182.3 +/- 3.6 cm; mass=
      87.4 +/- 12.5 kg) volunteered to participate. Subjects completed two random
      conditions on two separate days, consisting of either five sets of 10 maximal
      effort countermovement squat jumps (SJ) with 50 seconds' rest between sets or
      quiet sitting (SIT) for the time equated to the SJ duration (~4min). Immediately
      after each condition, subjects drank 75g of anhydrous glucose (CHO) in 100ml of
      water. Blood glucose measurements were taken via finger prick pre and immediately
      post SJ or SIT, and 5, 15, 30, and 60 min post. A 2*6 (condition * time) ANOVA
      revealed a significant interaction where SJ blood glucose was lower at 15 (114.0
      +/- 14.6 mg/dl) and 30 (142.1 +/- 22.5 mg/dl) min compared to SIT (15min 130.8 +/
      14.0 mg/dl and 30min 159.3 +/- 21.0 mg/dl). The current plyometric protocol
      attenuated CHO-induced blood glucose at 15 and 30 min. This may be due to
      increased physiological stress applied to the muscles, thus increasing muscular
      glucose uptake.

PMID- 29170710
TI  - Validation of the Functional Assessment of Chronic Illness Therapy-Spiritual Well
      Being-Expanded (FACIT-Sp-Ex) Across English and Spanish-Speaking
      Hispanics/Latinos: Results From the Hispanic Community Health Study/Study of
      Latinos Sociocultural Ancillary Study.
AB  - The validity of the Functional Assessment of Chronic Illness Therapy-Spiritual
      Well-Being (FACIT-Sp) has been examined in primarily non-Hispanics/Latinos with
      chronic illness. This study assessed the psychometric properties of the non
      illness, expanded FACIT-Sp (FACIT-Sp-Ex) in 5,163 U.S. Hispanic/Latino adults.
      Measures were interviewer-administered in English or Spanish. Confirmatory factor
      analyses indicated four factors: Meaning, Peace, Faith, and Relational. The scale
      demonstrated measurement invariance across English and Spanish. Subscales
      displayed adequate internal and test-retest reliability. Scores were positively
      associated with Duke Religion Index (DUREL) subscales. When all subscales were
      entered in a single model, Meaning and Peace were inversely associated with
      depressive symptoms and positively associated with HRQOL. Faith was positively
      associated with depressive symptoms and inversely associated with HRQOL.
      Relational was not associated with any outcome. FACIT-Sp-Ex subscales were
      generally more strongly associated than DUREL subscales with well-being. The
      FACIT-Sp-Ex appears to be a valid measure of spiritual well-being in U.S.
      Hispanics/Latinos.

PMID- 29170711
TI  - Correlation of Planned Dose to Area Postrema and Dorsal Vagal Complex with
      Clinical Symptoms of Nausea and Vomiting in Oropharyngeal Cancer (OPC) patients
      treated with radiation alone using IMRT.
AB  - Objective: To correlate the planned dose to the nausea center (NC) - area
      postrema (AP) and dorsal vagal complex (DVC) - with nausea and vomiting symptoms
      in OPC patients treated with IMRT without chemotherapy. We also investigated
      whether it was possible to reduce doses to the NC without significant degradation
      of the clinically accepted treatment plan. Methods: From 11/04 to 4/09, 37 OPC
      patients were treated with definitive or adjuvant IMRT without chemotherapy. Of
      these, only 23 patients had restorable plans and were included in this analysis.
      We contoured the NC with the assistance of an expert board-certified
      neuroradiologist. We searched for correlation between the delivered dose to the
      NC and patient-reported nausea and vomiting during IMRT. We used one-paired t
      test: two-sample assuming equal variances to compare differences in dose to NC
      between symptomatic and asymptomatic patients. We then replanned each case to
      determine if reduced dose to the NC could be achieved without compromising
      coverage to target volumes, increasing unwarranted hotspots or increasing dose to
      surrounding critical normal tissues. Results: Acute symptoms of nausea were as
      follows: Grade 0 (n=6), Grade 1 (n=13), Grade 2 (n=3), and Grade 3 (n=1).
      Patients with no complaints of nausea had a median dose to the DVC of 34.2 Gy
      (range 4.6-46.6 Gy) and AP of 32.6 Gy (range 7.0-41.4Gy); whereas those with any
      complaints of nausea had a median DVC dose of 40.4 Gy (range 19.3-49.4 Gy) and AP
      dose of 38.7 Gy (range 16.7-46.8 Gy) (p=0.04). Acute vomiting was as follows:
      Grade 0 (n=17), Grade 1 (n=4), Grade 2 (n=1), and Grade 3 (n=1). There was no
      significant difference in DVC or AP dose among those with and without vomiting
      symptoms (p=0.28).Upon replanning of each case to minimize dose to the NC, we
      were, on average, able to reduce the radiation dose to AP by 18% and DVC by 17%;
      while the average dose variations to the PTV coverage, brainstem, cord, temporal
      lobes, and cochlea were never greater than 3%. Hotspots increased by 2% for 3
      patients while hotspots for remaining patients were less than 2% variation.
      Conclusion: For OPC cancer patients treated with IMRT without chemotherapy, dose
      to AP and DVC may be associated with development of nausea. We were able to show
      that reducing doses substantially to the NC is achievable without significant
      alteration of the clinically accepted plan and may reduce the incidence and grade
      of nausea. As symptoms of nausea can be devastating to patients, one can consider
      routine contouring and constraining of the NC to minimize chances of having this
      complication.

PMID- 29170713
TI  - Modular synthesis of thiazoline and thiazole derivatives by using a cascade
      protocol.
AB  - Thiazolines and thiazoles are an integral part of numerous natural products, a
      number of drugs, and many useful molecules such as ligands for metal catalysis.
      We report the first common synthetic protocol for the synthesis of thiazoles and
      thiazolines. Novel molecules are efficiently synthesized by using readily
      available and inexpensive substrates. The reaction conditions are mild and pure
      products are obtained without work-up and column purification.

PMID- 29170714
TI  - Reduced Bimolecular Recombination in Blade-Coated, High-Efficiency, Small
      Molecule Solar Cells.
AB  - To realize the full promise of solution deposited photovoltaic devices requires
      processes compatible with high-speed manufacturing. We report the performance and
      morphology of blade-coated bulk heterojunction devices based on the small
      molecule donor p-DTS(FBTTh2)2 when treated with a post-deposition solvent vapor
      annealing (SVA) process. SVA with tetrahydrofuran improves the device performance
      of blade-coated films more than solvent additive processing (SA) with 1,8
      diiodooctane. In spin-coating, SA and SVA achieve similar device performance. Our
      optimized, blade coated, SVA devices achieve power conversion efficiencies over 8
      % and maintain high efficiencies in films up to ~ 250 nm thickness, providing
      valuable resilience to small process variations in high-speed manufacturing.
      Using impedance spectroscopy, we show that this advantageous behavior originates
      from highly suppressed bimolecular recombination in the SVA-treated films.
      Electron microscopy and grazing-incidence X-ray scattering experiments show that
      SA and SVA both produce highly crystalline donor domains, but SVA films have a
      radically smaller domain size compared to SA films. We attribute the different
      behavior to variations in initial nucleation density and relative ability of SVA
      and SA to control subsequent crystal growth.

PMID- 29170712
TI  - Chemical probes and inhibitors of bromodomains outside the BET family.
AB  - In the last five years, the development of inhibitors of bromodomains has emerged
      as an area of intensive worldwide research. Emerging evidence has implicated a
      number of non-BET bromodomains in the onset and progression of diseases such as
      cancer, HIV infection and inflammation. The development and use of small molecule
      chemical probes has been fundamental to pre-clinical evaluation of bromodomains
      as targets. Recent efforts are described highlighting the development of potent,
      selective and cell active non-BET bromodomain inhibitors and their therapeutic
      potential. Over half of typical bromodomains now have reported ligands, but those
      with atypical binding site residues remain resistant to chemical probe discovery
      efforts.

PMID- 29170715
TI  - Biocompatible, degradable thermoplastic polyurethane based on polycaprolactone
      block-polytetrahydrofuran-block-polycaprolactone copolymers for soft tissue
      engineering.
AB  - Biodegradable synthetic polymers have been widely used as tissue engineering
      scaffold materials. Even though they have shown excellent biocompatibility, they
      have failed to resemble the low stiffness and high elasticity of soft tissues
      because of the presence of massive rigid ester bonds. Herein, we synthesized a
      new thermoplastic polyurethane elastomer (CTC-PU(BET)) using poly ester ether
      triblock copolymer (polycaprolactone-block-polytetrahydrofuran-block
      polycaprolactone triblock copolymer, PCTC) as the soft segment, aliphatic
      diisocyanate (hexamethylene diisocyanate, HDI) as the hard segment, and
      degradable diol (bis(2-hydroxyethyl) terephthalate, BET) as the chain extender.
      PCTC inhibited crystallization and reduced the melting temperature of CTC
      PU(BET), and BET dramatically enhanced the thermal decomposition and hydrolytic
      degradation rate when compared with conventional polyester-based biodegradable
      TPUs. The CTC-PU(BET) synthesized in this study possessed a low tensile modulus
      and tensile strength of 2.2 MPa and 1.3 MPa, respectively, and an elongation-at
      break over 700%. Meanwhile, it maintained a 95.3% recovery rate and 90%
      resilience over ten cycles of loading and unloading. In addition, the TPU could
      be electrospun into both random and aligned fibrous scaffolds consisting of major
      microfibers and nanobranches. 3T3 fibroblast cell culture confirmed that these
      scaffolds outperformed the conventional biodegradable TPU scaffolds in terms of
      substrate-cellular interactions and cell proliferation. Considering the
      advantages of this TPU, such as ease of synthesis, low cost, low stiffness, high
      elasticity, controllable degradation rate, ease of processability, and excellent
      biocompatibility, it has great prospects to be used as a tissue engineering
      scaffold material for soft tissue regeneration.

PMID- 29170716
TI  - POSS-ProDOT Crosslinking of PEDOT.
AB  - Alkoxy-functionalized polythiophenes such as poly(3,4-ethylenedioxythiophene)
      (PEDOT) and poly(3,4-propylenedioxythiophene) (PProDOT) have become promising
      materials for a variety of applications including bioelectronic devices due to
      their high conductivity, relatively soft mechanical response, good chemical
      stability and excellent biocompatibility. However the long-term applications of
      PEDOT and PProDOT coatings are still limited by their relatively poor
      electrochemical stability on various inorganic substrates. Here, we report the
      synthesis of an octa-ProDOT-functionalized polyhedral oligomeric silsesquioxane
      (POSS) derivative (POSS-ProDOT) and its copolymerization with EDOT to improve the
      stability of PEDOT coatings. The POSS-ProDOT crosslinker was synthesized via
      thiol-ene "click" chemistry, and its structure was confirmed by both Nuclear
      Magnetic Resonance and Fourier Transform Infrared spectroscopies. PEDOT copolymer
      films were then electrochemically deposited with various concentrations of the
      crosslinker. The resulting PEDOT-co-POSS-ProDOT copolymer films were
      characterized by Cyclic Voltammetry, Electrochemical Impedance Spectroscopy,
      Ultraviolet-Visible spectroscopy and Scanning Electron Microscopy. The optical,
      morphological and electrochemical properties of the copolymer films could be
      systematically tuned with the incorporation of POSS-ProDOT. Significantly
      enhanced electrochemical stability of the copolymers was observed at intermediate
      levels of POSS-ProDOT content (3.1 wt%). It is expected that these highly stable
      PEDOT-co-POSS-ProDOT materials will be excellent candidates for use in
      bioelectronics devices such as neural electrodes.

PMID- 29170717
TI  - Stochasticity and determinism in cancer creation and progression.

PMID- 29170718
TI  - Resting state fMRI connectivity analysis as a tool for detection of abnormalities
      in five different cognitive networks of the brain in Multiple Sclerosis patients.
AB  - Objectives: Cognitive dysfunction is present in at least half of patients with
      Multiple Sclerosis. The purpose of this study was to examine functional
      connectivity abnormalities in patients with multiple sclerosis (MS) using resting
      state fMRI (rsfMRI). Methods: Conventional MRI, rsfMRI and diffusion tensor
      imaging (DTI) data was acquired from 10 patients with relapsing-remitting
      multiple sclerosis (RRMS) and 20 healthy controls. Cross-correlation of the
      resting state average signal among the voxels in each brain region of the five
      cognitive networks: default mode network (DMN), attention, verbal memory, memory,
      and visuospatial working memory network, was calculated. Voxelwise analyses were
      used to investigate fractional anisotropy (FA) of white matter tracts. The
      normalized gray matter (GM), white matter and thalamus volumes were calculated.
      Results: Compared to controls, significant deficit in MS patients at each of five
      networks, attention (p=0.026), DMN (p=0.004), verbal memory (p<0.001), memory
      (p=0.001), visuospatial working memory (p=0.003) was found. Significant reduction
      (p=0.034) in the normalized GM volume and asymmetry in thalamus volume (p=0.041)
      was detected in MS patients compared to controls. Conclusion: Wide spread of
      functional abnormalities are present within different cognitive networks in
      patients with RRMS, suggesting that DMN may not be sufficient for measurement of
      MS cognitive impairment. Larger and longitudinal studies should ascertain whether
      rsfMRI of cognitive networks and changes in GM and thalamus volume can be used as
      tools for assessment of cognition in clinical trials in MS.

PMID- 29170719
TI  - Subclinical Hypothyroidism and Its Association with Increased Cardiovascular
      Mortality.
AB  - Thyroid hormones play an important role in regulating different metabolism
      functions and multiple organs' performance. Changes in the thyroid hormone axis
      can lead to profound effects on the stability of vital organs and systems,
      especially the cardiovascular system. Hypothyroidism is classified according to
      the clinical presentation as overt and subclinical. There is some evidence
      supporting the benefits of thyroxine hormone replacement for subclinical
      hypothyroidism on cardiovascular mortality outcomes. However, the clinical
      relevance of measuring and treating high thyroid-stimulating hormone (TSH) levels
      in newly diagnosed heart failure patients with preserved ejection fraction
      requires further study. In this report, we review the current evidence regarding
      the prognostic significance of subclinical hypothyroidism in heart failure
      patients with preserved ejection fraction.

PMID- 29170721
TI  - A GENERAL FRAMEWORK FOR MINIMIZING ENERGY CONSUMPTION OF SERIES ELASTIC ACTUATORS
      WITH REGENERATION.
AB  - The use of actuators with inherent compliance, such as series elastic actuators
      (SEAs), has become traditional for robotic systems working in close contact with
      humans. SEAs can reduce the energy consumption for a given task compared to rigid
      actuators, but this reduction is highly dependent on the design of the SEA's
      elastic element. This design is often based on natural dynamics or a
      parameterized optimization, but both approaches have limitations. The natural
      dynamics approach cannot consider actuator constraints or arbitrary reference
      trajectories, and a parameterized elastic element can only be optimized within
      the given parameter space. In this work, we propose a solution to these
      limitations by formulating the design of the SEA's elastic element as a non
      parametric convex optimization problem, which yields a globally optimal
      conservative elastic element while respecting actuator constraints. Convexity is
      proven for the case of an arbitrary periodic reference trajectory with a SEA
      capable of energy regeneration. We discuss the optimization results for the tasks
      defined by the human ankle motion during level-ground walking and the natural
      motion of a single mass-spring system with a nonlinear spring. For all these
      tasks, the designed SEA reduces energy consumption and satisfies the actuator's
      constraints.

PMID- 29170720
TI  - Methionine adenosyltransferases in liver health and diseases.
AB  - Methionine adenosyltransferases (MATs) are essential for cell survival because
      they catalyze the biosynthesis of the biological methyl donor S
      adenosylmethionine (SAMe) from methionine and adenosine triphosphate (ATP).
      Mammalian cells express two genes, MAT1A and MAT2A, which encode two MAT
      catalytic subunits, alpha1 and alpha2, respectively. The alpha1 subunit organizes
      into dimers (MATIII) or tetramers (MATI). The alpha2 subunit is found in the
      MATII isoform. A third gene MAT2B, encodes a regulatory subunit beta, that
      regulates the activity of MATII by lowering the inhibition constant (Ki) for SAMe
      and the Michaelis constant (Km) for methionine. MAT1A expressed mainly in
      hepatocytes maintains the differentiated state of these cells whereas MAT2A and
      MAT2B are expressed in non-parenchymal cells of the liver (hepatic stellate cells
      [HSCs] and Kupffer cells) and extrahepatic tissues. A switch from the liver
      specific MAT1A to MAT2A has been observed during conditions of active liver
      growth and de-differentiation. Liver injury, fibrosis, and cancer are associated
      with MAT1A silencing and MAT2A/MAT2B induction. Even though both MAT1A and MAT2A
      are involved in SAMe biosynthesis, they exhibit distinct molecular interactions
      in liver cells. This review provides an update on MAT genes and their roles in
      liver pathologies.

PMID- 29170723
TI  - Homologue distribution patterns of 2,3,7,8-chloro-substituted PCDD/F in Bavarian
      soils.
AB  - Background: Soil-background values of PCDD/F concentrations are usually
      conveniently displayed as toxic equivalent (TEq), being a bulk parameter of all
      relevant 7 PCDD- and 10 PCDF-congeneres, chloro-subsidized at the 2nd, 3rd, 7th
      and 8th carbon atom. Data here are ample, not so survey on congenere/homologue
      patterns occurring in soils. The sufficient number of samples taken within this
      analysis allowed first a well-grounded evaluation. Results: OCDD proved to be the
      dominant congenere in all samples (forest and agriculture), however, in
      considerably different concentrations. As expected, highest level was detected in
      forest organic layers, followed by forest top soils, cropland- and grassland top
      soils. Although highest in concentration, OCDD only contributes to 0.17% (both
      forest organic- and top soil layer), respectively, 0.4% (cropland) and 0.3%
      (grassland) to TEq. The influence of lower chlorinated homologues on TEq is
      strongest in forest top soils (72%) followed by 67% (forest organic layers),
      cropland top soil (63%) and grassland (61%). Although all homologue patterns
      (forest and agriculture) give a fairly similar picture, a test of significance
      (chi2) proved a different population of forest samples. Conclusions: The
      resemblance of the homologue patterns throughout all utilization suggests that
      agent levels are explained mainly by diffuse atmospheric depositions rather than
      by specific land use input.

PMID- 29170722
TI  - What Drives False Memories in Psychopathology? A Case for Associative Activation.
AB  - In clinical and court settings, it is imperative to know whether posttraumatic
      stress disorder (PTSD) and depression may make people susceptible to false
      memories. We conducted a review of the literature on false memory effects in
      participants with PTSD, a history of trauma, or depression. When emotional
      associative material was presented to these groups, their levels of false memory
      were raised relative to those in relevant comparison groups. This difference did
      not consistently emerge when neutral or nonassociative material was presented.
      Our conclusion is supported by a quantitative comparison of effect sizes between
      studies using emotional associative or neutral, nonassociative material. Our
      review suggests that individuals with PTSD, a history of trauma, or depression
      are at risk for producing false memories when they are exposed to information
      that is related to their knowledge base.

PMID- 29170724
TI  - Deep tissue penetration of nanoparticles using pulsed-high intensity focused
      ultrasound.
AB  - Recently, ultrasound (US)-based drug delivery strategies have received attention
      to improve enhanced permeation and retention (EPR) effect-based passive targeting
      efficiency of nanoparticles in vitro and in vivo conditions. Among the US
      treatment techniques, pulsed-high intensity focused ultrasound (pHIFU) have
      specialized for improving tissue penetration of various macromolecules and
      nanoparticles without irreversible tissue damages. In this study, we have
      demonstrated that pHIFU could be utilized to improve tissue penetration of
      fluorescent dye-labeled glycol chitosan nanoparticles (FCNPs) in femoral tissue
      of mice. pHIFU could improve blood flow of the targeted-blood vessel in femoral
      tissue. In addition, tissue penetration of FCNPs was specifically increased 5.7-,
      8- and 9.3-folds than that of non-treated (0 W pHIFU) femoral tissue, when the
      femoral tissue was treated with 10, 20 and 50 W of pHIFU, respectively. However,
      tissue penetration of FCNPs was significantly reduced after 3 h post-pHIFU
      treatment (50 W). Because overdose (50 W) of pHIFU led to irreversible tissue
      damages, including the edema and chapped red blood cells. These overall results
      support that pHIFU treatment can enhance the extravasation and tissue penetration
      of FCNPs as well as induce irreversible tissue damages. We expect that our
      results can provide advantages to optimize pHIFU-mediated delivery strategy of
      nanoparticles for further clinical applications.

PMID- 29170726
TI  - Accuracy to detection timing for assisting repetitive facilitation exercise
      system using MRCP and SVM.
AB  - This paper presents a feasibility study of a brain-machine interface system to
      assist repetitive facilitation exercise. Repetitive facilitation exercise is an
      effective rehabilitation method for patients with hemiplegia. In repetitive
      facilitation exercise, a therapist stimulates the paralyzed part of the patient
      while motor commands run along the nerve pathway. However, successful repetitive
      facilitation exercise is difficult to achieve and even a skilled practitioner
      cannot detect when a motor command occurs in patient's brain. We proposed a brain
      machine interface system for automatically detecting motor commands and
      stimulating the paralyzed part of a patient. To determine motor commands from
      patient electroencephalogram (EEG) data, we measured the movement-related
      cortical potential (MRCP) and constructed a support vector machine system. In
      this paper, we validated the prediction timing of the system at the highest
      accuracy by the system using EEG and MRCP. In the experiments, we measured the
      EEG when the participant bent their elbow when prompted to do so. We analyzed the
      EEG data using a cross-validation method. We found that the average accuracy was
      72.9% and the highest at the prediction timing 280 ms. We conclude that 280 ms is
      the most suitable to predict the judgment that a patient intends to exercise or
      not.

PMID- 29170725
TI  - Reduction of Cognitive Decline in Patients with or at High Risk for Diabetes.
AB  - Purpose of review: The incidence of Alzheimer's disease and related disorders is
      expected to triple by 2050. People with type 2 diabetes and prediabetes have a
      higher risk of cognitive dysfunction, including Alzheimer's disease and vascular
      dementia. Controversy remains about when and how to prevent and treat cognitive
      dysfunction in people with or at high risk of diabetes. Recent findings: In our
      review of ongoing clinical trials, we have found that there has been an increase
      in the number of studies assessing the efficacy of pharmacological and non
      pharmacological approaches to prevent or slow down cognitive impairment among
      people with or at high risk of diabetes. Summary: Despite the considerable risk
      of cognitive impairment in people with diabetes and prediabetes, there is not
      enough evidence to support a specific treatment to prevent or slow mild cognitive
      impairment, or progression to Alzheimer's disease or related disorders. Several
      ongoing trials are attempting to identify the usefulness of several compounds, as
      well as lifestyle changes including exercise and diet. Direct mechanisms linking
      diabetes to cognitive decline have not been elucidated.

PMID- 29170727
TI  - Grasping state estimation of printable soft gripper using electro-conductive
      yarn.
AB  - Automatic handling of many types of food materials are required to realize the
      automation of production of commercially prepared box lunches. A printable soft
      gripper was developed for food handling which is simple to produce with a 3D
      printer. However, the sensing ability of the printable soft gripper was not
      discussed in previous research. In this paper, a novel method for estimating the
      grasping state of a printable soft gripper using electro-conductive yarn is
      presented. Electro-conductive yarn is a conductive material, and the resistance
      of strings is changed by stretching. It is less expensive than other sensors that
      can be used for measurement of grasping state. Additionally, it is easy to
      assemble and disassemble by hand. Electro-conductive yarn is applied to a
      prototype printable soft gripper, and the proposed estimation method is verified
      experimentally. From the experimental results, the estimated grasping state from
      the resistance of the electro-conductive yarn coincides with the actual grasping
      state of the gripper. Our proposed method of using electro-conductive yarn was
      successful for estimating the grasping state of a printable soft gripper.

PMID- 29170729
TI  - Aerial pruning mechanism, initial real environment test.
AB  - In this research, a pruning mechanism for aerial pruning tasks is tested in a
      real environment. Since the final goal of the aerial pruning robot will be to
      prune tree branches close to power lines, some experiments related to wireless
      communication and pruning performance were conducted. The experiments consisted
      of testing the communication between two XBee RF modules for monitoring purposes
      as well as testing the speed control of the circular saw used for pruning tree
      branches. Results show that both the monitoring and the pruning tasks were
      successfully done in a real environment.

PMID- 29170728
TI  - Dynamics and control of separable coupled rigid body systems.
AB  - This paper explores the dynamics of separable coupled rigid body systems, a
      special class of constrained rigid body systems. These are defined as two systems
      that interact with each other by forces of contact, resulting in a reduction in
      dimensionality and complexity. The mechanics and consequences of this reduction
      are investigated here. The basic hypothesis and an example of the reduction in
      two successive steps are formulated. A simple mechanical biped model is developed
      and analyzed in some details by both system theoretical concepts and simulations.
      The main contribution of this work is the novel extension to the known dynamics
      of constrained rigid bodies. The modular, versatile and systematic formulation
      presented here is computationally efficient and has many applications in the
      studies of the human neuro-musculoskeletal system, robotic systems and humanoids,
      as well as clinical and sports biomechanics applications. Computer simulations
      are provided to demonstrate the feasibility and effectiveness of the methodology.

PMID- 29170730
TI  - Improving low-cost inertial-measurement-unit (IMU)-based motion tracking accuracy
      for a biomorphic hyper-redundant snake robot.
AB  - This paper develops and experimentally validates a 3D-printed snake robot
      prototype. Its structure is designed to allocate limited room for each functional
      module (including an external power module, battery power module, the wireless
      control and transmission module and some detective sensors), so as to ensure the
      snake robot works in different environments. In order to control and track the
      snake robot, a low-cost MEMS-IMU (micro-electro-mechanical systems inertial
      measurement unit)-based snake robot motion tracking system is developed. Three
      algorithms (low-pass filter, baseline calibration, and Kalman filter) are used to
      eliminate noise from IMU's acceleration data, thus minimizing the noise influence
      to tracking accuracy. Through signal processing, the IMU acceleration data can be
      effectively used for motion tracking. The result from the video tracking software
      is employed as a reference for comparison, so as to evaluate the motion tracking
      algorithm efficiency. The comparison results demonstrate high efficiency of the
      proposed IMU-based motion tracking algorithm.

PMID- 29170731
TI  - Robot-aided electrospinning toward intelligent biomedical engineering.
AB  - The rapid development of robotics offers new opportunities for the traditional
      biofabrication in higher accuracy and controllability, which provides great
      potentials for the intelligent biomedical engineering. This paper reviews the
      state of the art of robotics in a widely used biomaterial fabrication process,
      i.e., electrospinning, including its working principle, main applications,
      challenges, and prospects. First, the principle and technique of electrospinning
      are introduced by categorizing it to melt electrospinning, solution
      electrospinning, and near-field electrospinning. Then, the applications of
      electrospinning in biomedical engineering are introduced briefly from the aspects
      of drug delivery, tissue engineering, and wound dressing. After that, we conclude
      the existing problems in traditional electrospinning such as low production,
      rough nanofibers, and uncontrolled morphology, and then discuss how those
      problems are addressed by robotics via four case studies. Lastly, the challenges
      and outlooks of robotics in electrospinning are discussed and prospected.

PMID- 29170732
TI  - Changes in Saving Cognitions Mediate Hoarding Symptom Change in Cognitive
      Behavioral Therapy for Hoarding Disorder.
AB  - Cognitive-behavioral therapy (CBT) is an empirically-supported treatment for
      hoarding disorder (HD). However, meta-analytic studies suggest that CBT is only
      modestly effective, and a significant number of individuals with HD remain
      symptomatic following treatment. To inform the development of more effective and
      targeted treatments, it will be important to clarify the mechanisms of treatment
      response in CBT for HD. To this end, the current study examined whether change in
      maladaptive saving beliefs mediated symptom change in CBT for HD. Sixty-two
      patients with primary HD completed measures of maladaptive saving cognitions and
      hoarding severity at pre-, mid-, and post-CBT. Results showed that change in
      saving cognitions mediated change in all three domains of HD symptoms (i.e.,
      acquiring, difficulty discarding, and excessive clutter), suggesting that
      cognitive change may be a mechanism of treatment response in CBT. The findings
      indicate that cognitive change may have an impact on treatment outcomes, and are
      discussed in terms of cognitive-behavioral theory of HD and potential ways in
      which to enhance belief change in treatment.

PMID- 29170733
TI  - Editorial: Metabolism As a Therapeutic Target.

PMID- 29170734
TI  - The Prevalence and Distribution of Spina Bifida in a Single Major Referral Center
      in Malaysia.
AB  - Background: The aim of this study is to review the medical history of patients
      with spina bifida, encompassing both aperta and occulta types born between the
      years 2003 until 2016, spanning a 13-year time period. We assessed each patient
      and maternal parent information, details of the defects, and conditions
      associated with the primary defect. We also include information on patients'
      ambulation and education level (where available). Methods: Data from the
      Department of Patient Information University of Malaya Medical Centre (UMMC),
      Malaysia was captured from spina bifida patients (ICD10: Q05 spina bifida). Data
      involved patients referred to UMMC between 2003 and 2016 and/or born in UMMC
      within that particular time frame. We filtered and extracted the information
      according to the data of clinical examination, medical review, and social history
      provided in the medical records. Results: A total of 86 patient records with
      spina bifida were analyzed. Spina bifida prevalence rate in this study ranged
      from 1.87 to 8.9 per 1,000 live births depending on weightage. We note that
      ethnicity was a factor whereby the highest numbers of spina bifida were from
      Malays (n = 36, 41.86%), followed by equal numbers of Chinese and Indians (n =
      24, 27.91%). The highest number of diagnoses reported was myelomeningocele type
      spina bifida (n = 39, 45.35%). The most common site of the spina bifida lesion
      was located at the lumbar region irrespective of aperta or occulta types (n = 23,
      26.74%). Data on other associated phenotypes of spina bifida such as
      hydrocephalus and encephalocele was also captured at 37.21% (n = 32) and 1.16% (n
      = 1), respectively. In terms of mobility, 32.84% (n = 22/67) of patients between
      the ages 4 and 16 years old were found to be mobile. As many as 36.07% of
      patients ranging from 5 to 16 years of age (n = 22/61) received formal education
      ranging from preschool to secondary school. Conclusion: The prevalence of spina
      bifida in UMMC is as according to international statistics which is in the range
      of 0.5-10 per 1,000 live births. Majority of the reported cases were males,
      Malays, full term babies, and of the myelomeningocele phenotype located at the
      lumbar region.

PMID- 29170736
TI  - Transcriptome Landscape at Different Developmental Stages of a Drought Tolerant
      Cultivar of Flax (Linum usitatissimum).

PMID- 29170738
TI  - BIM-Sim: Interactive Simulation of Broadband Imaging Using Mie Theory.
AB  - Understanding the structure of a scattered electromagnetic (EM) field is critical
      to improving the imaging process. Mechanisms such as diffraction, scattering, and
      interference affect an image, limiting the resolution, and potentially
      introducing artifacts. Simulation and visualization of scattered fields thus
      plays an important role in imaging science. However, EM fields are high
      dimensional, making them time-consuming to simulate, and difficult to visualize.
      In this paper, we present a framework for interactively computing and visualizing
      EM fields scattered by micro and nano-particles. Our software uses graphics
      hardware for evaluating the field both inside and outside of these particles. We
      then use Monte-Carlo sampling to reconstruct and visualize the three-dimensional
      structure of the field, spectral profiles at individual points, the structure of
      the field at the surface of the particle, and the resulting image produced by an
      optical system.

PMID- 29170737
TI  - How Are Substrate Binding and Catalysis Affected by Mutating Glu127 and Arg161 in
      Prolyl-4-hydroxylase? A QM/MM and MD Study.
AB  - Prolyl-4-hydroxylase is a vital enzyme for human physiology involved in the
      biosynthesis of 4-hydroxyproline, an essential component for collagen formation.
      The enzyme performs a unique stereo- and regioselective hydroxylation at the C4
      position of proline despite the fact that the C5 hydrogen atoms should be
      thermodynamically easier to abstract. To gain insight into the mechanism and find
      the origin of this regioselectivity, we have done a quantum mechanics/molecular
      mechanics (QM/MM) study on wildtype and mutant structures. In a previous study
      (Timmins et al., 2017) we identified several active site residues critical for
      substrate binding and positioning. In particular, the Glu127 and Arg161 were
      shown to form multiple hydrogen bonding and ion-dipole interactions with
      substrate and could thereby affect the regio- and stereoselectivity of the
      reaction. In this work, we decided to test that hypothesis and report a QM/MM and
      molecular dynamics (MD) study on prolyl-4-hydroxylase and several active site
      mutants where Glu127 or Arg161 are mutated for Asp, Gln, or Lys. Thus, the R161D
      and R161Q mutants give very high barriers for hydrogen atom abstraction from any
      proline C-H bond and therefore will be inactive. The R161K mutant, by contrast,
      sees the regio- and stereoselectivity of the reaction change but still is
      expected to hydroxylate proline at room temperature. By contrast, the Glu127
      mutants E127D and E127Q show possible changes in regioselectivity with the former
      being more probable to react compared to the latter.

PMID- 29170735
TI  - A Novel Strategy to Predict Carcinogenicity of Antiparasitics Based on a
      Combination of DNA Lesions and Bacterial Mutagenicity Tests.
AB  - Genotoxicity and carcinogenicity testing of pharmaceuticals prior to
      commercialization is requested by regulatory agencies. The bacterial mutagenicity
      test was considered having the highest accuracy of carcinogenic prediction.
      However, some evidences suggest that it always results in false-positive
      responses when the bacterial mutagenicity test is used to predict
      carcinogenicity. Along with major changes made to the International Committee on
      Harmonization guidance on genotoxicity testing [S2 (R1)], the old data
      (especially the cytotgenetic data) may not meet current guidelines. This review
      provides a compendium of retrievable results of genotoxicity and animal
      carcinogenicity of 136 antiparasitics. Neither genotoxicity nor carcinogenicity
      data is available for 84 (61.8%), while 52 (38.2%) have been evaluated in at
      least one genotoxicity or carcinogenicity study, and only 20 (14.7%) in both
      genotoxicity and carcinogenicity studies. Among 33 antiparasitics with at least
      one old result in in vitro genotoxicity, 15 (45.5%) are in agreement with the
      current ICH S2 (R1) guidance for data acceptance. Compared with other
      genotoxicity assays, the DNA lesions can significantly increase the accuracy of
      prediction of carcinogenicity. Together, a combination of DNA lesion and
      bacterial tests is a more accurate way to predict carcinogenicity.

PMID- 29170739
TI  - Market Impacts of Reducing the Prevalence of Bovine Respiratory Disease in United
      States Beef Cattle Feedlots.
AB  - Bovine respiratory disease (BRD) is a common endemic disease among North American
      feedlot cattle. BRD can lead to significant economic losses for individual beef
      cattle feedlot producers through mortality and morbidity. With promising new
      management and technology research that could reduce BRD prevalence, this study
      evaluates the potential impacts of a reduction of BRD in the US beef cattle
      feedlot sector. Using a multi-market, multi-commodity partial equilibrium
      economic model of the US agricultural industry, we evaluate the market impacts of
      reduced BRD to producers from various livestock, meat, and feedstuffs industries.
      We find that as morbidity and mortality is reduced, beef cattle producers
      experience losses due to increased supplies (lower beef cattle prices) and
      increased demand for feedstuff (higher feedstuff prices). Beef cattle processors
      see gains as the price of beef cattle is lower, whereas feedstuff producers gain
      from higher feedstuff prices. Producers in the allied industries (pork, lamb,
      poultry, and eggs) see a small reduction in returns as consumers substitute with
      less expensive beef products. Consumers see gains in welfare as the increase in
      beef cattle supply results in lower beef prices. These lower beef prices more
      than offset the small increases in pork, lamb, poultry, and egg prices. Overall,
      the potential economic welfare change due to management and technologies that
      reduce BRD is a net gain for the US society as a whole.

PMID- 29170740
TI  - Tip Design for Safety of Steerable Needles for Robot-Controlled Brain Insertion.
AB  - Background: Current practice in neurosurgical needle insertion is limited by the
      straight trajectories inherent with rigid probes. One technique allowing
      curvilinear trajectories involves flexible bevel-tipped needles, which bend
      during insertion due to their asymmetry. In the brain, safety will require
      avoidance of the sharp tips often used in laboratory studies, in favor of a more
      rounded profile. Steering performance, on the other hand, requires maximal
      asymmetry. Design of safe bevel-tipped brain needles thus involves management of
      this tradeoff by adjusting needle gauge, bevel angle, and fillet (or tip) radius
      to arrive at a design that is suitably asymmetrical while producing strain,
      strain rate, and stress below the levels that would damage brain tissue. Methods:
      Designs with a variety of values of needle radius, bevel angle, and fillet radius
      were evaluated in finite-element simulations of simultaneous insertion and
      rotation. Brain tissue was modeled as a hyperelastic, linear viscoelastic
      material. Based on the literature available, safety thresholds of 0.19 strain, 10
      s-1 strain rate, and 120 kPa stress were used. Safe values of needle radius,
      bevel angle, and fillet radius were selected, along with an appropriate velocity
      envelope for safe operation. The resulting needle was fabricated and compared
      with a Sedan side-cutting brain biopsy needle in a study in the porcine model in
      vivo (N=3). Results: The prototype needle selected was 1.66 mm in diameter, with
      bevel angle of 10 degrees  and fillet radius of 0.25 mm. Upon examination of
      postoperative CT and histological images, no differences in tissue trauma or
      hemorrhage were noted between the prototype needle and the Sedan needle.
      Conclusions: The study indicates a general design technique for safe bevel-tipped
      brain needles based on comparison with relevant damage thresholds for strain,
      strain rate, and stress. The full potential of the technique awaits the
      determination of more exact safety thresholds.

PMID- 29170741
TI  - Small-scale Triton X-114 Extraction of Hydrophobic Proteins.
AB  - Here we introduce a protocol for Triton X-114 extraction which we used in our
      recently-published paper (Taguchi et al., 2013). It is a versatile method to
      concentrate or partially purify hydrophobic proteins. The presented protocol is
      based on the protocol published by Bordier (Bordier, 1981) but more simplified
      and down-scaled for more small-scale and simpler use (Taguchi et al., 2013).
      Triton X-114 (TX114) is a non-ionic detergent which has a relatively low clouding
      point at 22  degrees C and separates into detergent (Det) and aqueous (Aq) phase
      at temperatures above the clouding point. During phase separation, hydrophobic
      solutes in the TX114 solution are sequestered to the Det phase, while hydrophilic
      solutes are sequestered to the Aq phase. Utilizing this phenomenon, TX114
      extraction is a very versatile technique to efficiently concentrate hydrophobic
      proteins, especially glycosylphosphatidylinositol (GPI)-anchored proteins like
      the prion protein (PrP), because they have substantial amounts of highly
      hydrophobic moieties. Besides, phase separation using TX114 tolerates a variety
      of conditions, e.g. different pH or relatively low concentrations of guanidine
      hydrochloride. Since the hydrophobic proteins are sequestered to the Det phase as
      long as the phase separation occurs, and if the hydrophobicity of the protein of
      interest is not affected by pH or denaturant, this technique can be also utilized
      to change buffers or to remove denaturants. When using enzymes or proteases which
      maintain activities in detergent solutions, TX114 can also be used to separate
      hydrophobic from the water-soluble hydrophilic moieties upon enzymatic digestion
      of proteins, as done by us using in vitro digestion of PrP with
      phosphatidylinositol-specific phospholipase C (Taguchi et al., 2013).

PMID- 29170742
TI  - Small-scale Subcellular Fractionation with Sucrose Step Gradient.
AB  - Here, we introduce the protocol for small-scale and simple subcellular
      fractionation used in our recent publication (Taguchi et al., 2013), which uses
      homogenization by passing through needles and sucrose step-gradient. Subcellular
      fractionation is a very useful technique but usually a large number of cells are
      required. Because we needed subcellular fractionation of transiently-transfected
      cells, we developed a protocol for smaller numbers of cells. Our protocol for the
      subcellular fractionation is based on the protocol published by de Araujo and
      Huber (de Araujo et al., 2007), although substantial modifications have been made
      according to our experiences and information from personal communications. As
      optimal conditions seem to vary between cell lines, we advise to further modify
      the protocol to optimize for individual experiments. Our method is simple but
      sufficient for analysis of integral membrane proteins or proteins anchored to
      organelles by glycosylphosphatidylinositol or other lipid anchors, e.g. prion
      protein. However, proteins non-covalently attached to membranes or membrane
      proteins of organelles seem to be more prone to dissociation from the organelles
      during preparation and, if these proteins are the object of study, further
      modifications might be necessary. Unlike in a continuous gradient, where a
      protein of interest is scattered over a wide range, step-gradient fractionation
      is advantageous in detection of relatively small amounts of proteins from small
      scale experiments, because it concentrates the protein of interest in one
      fraction, if an appropriate combination of sucrose concentrations is used.

PMID- 29170743
TI  - Infant Rabbit Colonization Competition Assays.
AB  - Enteric pathogenic bacteria such as Vibrio cholerae and enteropathogenic
      Escherichia coli (E. coli) cause life-threatening diarrheal diseases that have
      afflicted humans for centuries. Understanding the effectors required for
      intestinal colonization is very important to research on bacteria pathogenesis,
      and is also important to testing new therapeutics and development of the novel
      vaccines. Here, we describe the Infant Rabbit Colonization Competition Assay, a
      variant method of the powerful, nonsurgical animal model reported by Ritchie et
      al. (2010). In our modified assay, wild type and mutant strains are mixed
      together and inoculated into 2-day-old New Zealand white rabbits. The competitive
      index for each mutant measures the colonization capacity of the mutant relative
      to its wild type parental strain in the gastrointestinal tract. Compared to the
      traditional Sucking Mice model, the clinical and histologic signs of Vibrio
      cholerae (V. cholera)-induced disease of infant rabbits more closely resemble
      human cholera. The larger input bacteria amount of this model also facilitates
      high-throughput screens, such as Tn-Seq technology (Fu et al., 2013).

PMID- 29170744
TI  - Murine in vivo CD8+ T Cell Killing Assay.
AB  - Antigen-specific killing ability of effector CD8+ T cells is critical for
      protective immunity against infection. Here, we describe in vivo cytotoxic T cell
      assay to examine effector function of antigen-specific CD8+ T cells. Mice
      infected with Listeria monocytogenes (L. monocytogenes) expressing chicken
      ovalbumin as a model antigen mount ovalbumin-specific CD8+ T cell responses.
      Effector CD8+ T cell function in vivo is determined by mixed transfer of OVA
      peptide-pulsed target cells with control target cells into the previously
      immunized mice. Difference in CFSE expression levels clearly marks two distinct
      populations: Antigen-pulsed target cells-CFSElow vs. unpulsed target cells
      CFSEhi. The frequencies between antigen-pulsed target cells and control target
      cells are used as readouts of antigen-specific killing.

PMID- 29170745
TI  - RNA Chromatin Immunoprecipitation (RNA-ChIP) in Caenorhabditis elegans.
AB  - The RNA chromatin immunoprecipitation assay (RNA-ChIP) allows detection and
      quantification of RNA-protein interactions using in vivo cross-linking with
      formaldehyde followed by immunoprecipitation of the RNA-protein complexes. Here
      we describe the RNA-ChIP protocol that we have adapted for Caenorhabditis elegans
      (C. elegans) to detect interaction between the nuclear Argonaute CSR-1
      (chromosome segregation and RNAi deficient) protein and its target nascent RNAs.
      We have used a transgenic strain expressing a recombinant long isoform of CSR-1
      protein fused with N-terminal 3x FLAG epitope.

PMID- 29170746
TI  - Artificial Optogenetic TRN Stimulation of C. elegans.
AB  - Optogenetics is a powerful tool for manipulating neuronal activity with high
      temporal and spatial precision. In the nematode C. elegans optogentics is
      especially useful and easy to apply. This is because C. elegans is translucent,
      so its neurons are highly accessible to optic stimulation. In addition, many of
      its neurons can be exclusively targeted using cell-specific promoters. We have
      recently taken advantage of optogentics to deliver artificial patterns of
      prolonged activation to a class of mechanosensory neurons, called touch receptor
      neurons (TRNs) in worms that lack touch sensation due to a genetic mutation. Our
      aim was to examine whether we can counteract the effects of sensory loss by
      artificially activating the sensory neurons. Here we describe in detail the
      various components of the protocol that we used. This consists of exposing worms
      expressing the light-sensitive ion channel Channelrohdopsin 2 (ChR2) in TRNs to
      long-term random flashes of light.

PMID- 29170747
TI  - Lung Section Staining and Microscopy.
AB  - Our protocol describes immunofluorescent staining, hematoxylin and eosin staining
      and Masson's trichrome staining on lung sections.

PMID- 29170748
TI  - Fluorophore Labeling, Nanodisc Reconstitution and Single-molecule Observation of
      a G Protein-coupled Receptor.
AB  - Activation of G protein-coupled receptors (GPCRs) by agonist ligands is mediated
      by a transition from an inactive to active receptor conformation. We describe a
      novel single-molecule assay that monitors activation-linked conformational
      transitions in individual GPCR molecules in real-time. The receptor is site
      specifically labeled with a Cy3 fluorescence probe at the end of trans-membrane
      helix 6 and reconstituted in phospholipid nanodiscs tethered to a microscope
      slide. Individual receptor molecules are then monitored over time by single
      molecule total internal reflection fluorescence microscopy, revealing spontaneous
      transitions between inactive and active-like conformations. The assay provides
      information on the equilibrium distribution of inactive and active receptor
      conformations and the rate constants for conformational exchange. The experiments
      can be performed in the absence of ligands, revealing the spontaneous
      conformational transitions responsible for basal signaling activity, or in the
      presence of agonist or inverse agonist ligands, revealing how the ligands alter
      the dynamics of the receptor to either stimulate or repress signaling activity.
      The resulting mechanistic information is useful for the design of improved GPCR
      targeting drugs. The single-molecule assay is described in the context of the
      beta2 adrenergic receptor, but can be extended to a variety of GPCRs.

PMID- 29170749
TI  - In vitro AMPylation Assays Using Purified, Recombinant Proteins.
AB  - Post-translational protein modifications (PTMs) orchestrate the activity of
      individual proteins and ensure their proper function. While modifications such as
      phosphorylation or glycosylation are well understood, more unusual modifications,
      including nitrosylation or AMPylation remain comparatively poorly characterized.
      Research on protein AMPylation-which refers to the covalent addition of an AMP
      moiety to the side chains of serine, threonine or tyrosine-has undergone a
      renaissance (Yarbrough et al., 2009; Engel et al., 2012; Ham et al., 2014;
      Woolery et al., 2014; Preissler et al., 2015; Sanyal et al., 2015; Truttmann et
      al., 2016; Truttmann et al., 2017). The identification and characterization of
      filamentation (fic) domain-containing AMPylases sparked new interest in this PTM
      (Kinch et al., 2009; Yarbrough et al., 2009). Based on recent in vivo and in
      vitro studies, we now know that secreted bacterial AMPylases covalently attach
      AMP to members of the Rho family of GTPases, while metazoan AMPylases modify
      HSP70 family proteins in the cytoplasm and the endoplasmic reticulum (ER) (Itzen
      et al., 2011; Hedberg and Itzen, 2015; Truttmann and Ploegh, 2017). AMPylation is
      thought to trap HSP70 in a primed yet transiently disabled state that cannot
      participate in protein refolding reactions (Preissler et al., 2015). In vitro
      AMPylation experiments are key to assess the activity, kinetics and specificity
      of protein AMPylation catalyzed by pro- and eukaryotic enzymes. These simple
      assays require recombinant AMPylases, target proteins (Rho GTPases, HSP70s), as
      well as ATP as a nucleotide source. Here, we describe strategies to qualitatively
      and quantitatively study protein AMPylation in vitro.

PMID- 29170750
TI  - Gene Dosage Experiments in Enterobacteriaceae Using Arabinose-regulated
      Promoters.
AB  - This protocol is used to assay the effect of protein over-expression on fitness
      of E. coli. It is based on a plasmid expression of a protein of interest from an
      arabinose-regulated pBAD promoter followed by the measurement of the
      intracellular protein abundance by Western blot along with the measurement of
      growth parameters of E. coli cell expressing this protein.

PMID- 29170751
TI  - Accurate, Streamlined Analysis of mRNA Translation by Sucrose Gradient
      Fractionation.
AB  - The efficiency with which proteins are produced from mRNA molecules can vary
      widely across transcripts, cell types, and cellular states. Methods that
      accurately assay the translational efficiency of mRNAs are critical to gaining a
      mechanistic understanding of post-transcriptional gene regulation. One way to
      measure translational efficiency is to determine the number of ribosomes
      associated with an mRNA molecule, normalized to the length of the coding
      sequence. The primary method for this analysis of individual mRNAs is sucrose
      gradient fractionation, which physically separates mRNAs based on the number of
      bound ribosomes. Here, we describe a streamlined protocol for accurate analysis
      of mRNA association with ribosomes. Compared to previous protocols, our method
      incorporates internal controls and improved buffer conditions that together
      reduce artifacts caused by non-specific mRNA-ribosome interactions. Moreover, our
      direct-from-fraction qRT-PCR protocol eliminates the need for RNA purification
      from gradient fractions, which greatly reduces the amount of hands-on time
      required and facilitates parallel analysis of multiple conditions or gene
      targets. Additionally, no phenol waste is generated during the procedure. We
      initially developed the protocol to investigate the translationally repressed
      state of the HAC1 mRNA in S. cerevisiae, but we also detail adapted procedures
      for mammalian cell lines and tissues.

PMID- 29170752
TI  - Proximal Ligation Assay (PLA) on Lung Tissue and Cultured Macrophages to
      Demonstrate Protein-protein Interaction.
AB  - In this protocol, we describe proximal ligation assay (PLA), an antibody-based
      detection method for protein-protein interaction. This method relies on specific
      binding of individual primary antibodies to the two putative interacting
      proteins. The primary antibodies need to have different hosts. The secondary
      antibodies against the two hosts have complementary oligonucleotide moieties
      attached to them. If the two antigens are in close proximity (presumably
      interacting with each other), the complementary oligonucleotides can anneal and
      fluorescent nucleotides can be incorporated in a single DNA polymerization step.
      Under a microscope, these reactions appear as punctate fluorescent spots,
      indicating successful PLA reaction and suggesting protein-protein interaction
      between the two antigens.

PMID- 29170753
TI  - The Object Context-place-location Paradigm for Testing Spatial Memory in Mice.
AB  - This protocol was originally designed to examine long-term spatial memory in
      PKMzeta knockout (i.e., PKMzeta-null) mice (Tsokas et al., 2016). Our main goal
      was to test whether the ability of these animals to maintain previously acquired
      spatial information was sensitive to the type and complexity of the spatial
      information that needs to be remembered. Accordingly, we modified and combined
      into a single protocol, three novelty-preference tests, specifically the object
      in-context, object-in-place and object-in-location tests, adapted from previous
      studies in rodents (Mumby et al., 2002; Langston and Wood, 2010; Barker and
      Warburton, 2011). During the training (learning) phase of the procedure, mice are
      repeatedly exposed to three different environments in which they learn the
      spatial arrangement of an environment-specific set of non-identical objects.
      After this learning phase is completed, each mouse receives three different
      memory tests configured as environment mismatches, in which the previously
      learned objects-in-space configurations have been modified from the original
      training situation. The mismatch tests differ in their cognitive demands due to
      the type of spatial association that is manipulated, specifically evaluating
      memory for object-context and object-place associations. During each memory test,
      the time differential spent exploring the novel (misplaced) and familiar objects
      is computed as an index of novelty discrimination. This index is the behavioral
      measure of memory recall of the previously acquired spatial associations.

PMID- 29170754
TI  - Quadrature Demodulation of a Quantum Dot Optical Response to Faint Light Fields.
AB  - The amplitude and phase of a material's nonlinear optical response provide
      insight into the underlying electronic dynamics that determine its optical
      properties. Phase-sensitive nonlinear spectroscopy techniques are widely
      implemented to explore these dynamics through demodulation of the complex optical
      signal field into its quadrature components; however, complete reconstruction of
      the optical response requires measuring both the amplitude and phase of each
      quadrature, which is often lost in standard detection methods. Here, we implement
      a heterodyne-detection scheme to fully reconstruct the amplitude and phase
      response of spectral hole-burning from InAs/GaAs charged quantum dots. We observe
      an ultra-narrow absorption profile and a corresponding dispersive lineshape of
      the phase, which reflect the nanosecond optical coherence time of the charged
      exciton transition. Simultaneously, the measurements are sensitive to electron
      spin relaxation dynamics on a millisecond timescale, as this manifests as a
      magnetic-field dependent delay of the amplitude and phase modulation. Appreciable
      amplitude modulation depth and nonlinear phase shift up to ~0.09*pi radians (16
      degrees ) are demonstrated, providing new possibilities for quadrature modulation
      at faint photon levels with several independent control parameters, including
      photon number, modulation frequency, detuning, and externally applied fields.

PMID- 29170755
TI  - Accountable care organizations and prostate cancer care.
AB  - Purpose: Accountable care organizations have the potential to increase the value
      of healthcare by improving population health and enhanced financial stewardship.
      How practice context modifies effects on a specialty-focused disease, such as
      prostate cancer care, has implications for their success. Methods: We performed a
      retrospective cohort study of newly diagnosed men with prostate cancer between
      2012 and 2013 using national Medicare data. Practice affiliation (small single
      specialty, large single-specialty, multispecialty groups) and accountable care
      organization alignment were measured at the patient level. Generalized linear
      multivariable models were fitted to derive adjusted rates of treatment and
      spending for the 12-month period after diagnosis according to accountable care
      organization alignment and practice affiliation. Results: Of 15,640 patients with
      newly diagnosed prostate cancer, 1,100 (7.0%) were aligned with accountable care
      organizations. Patients in these organizations had similar use of curative
      treatment to those not in accountable care organizations (71.4% vs. 70.0%,
      respectively; p=0.33), which did not vary with practice affiliation (p=0.39).
      Adjusted spending was higher among patients in accountable care organizations
      ($20,916 vs. $19,773, p=0.03); however, this relationship was independent of the
      practice affiliation (p=0.90). Higher accountable care organization penetration
      within a practice was associated with increased spending (p<0.05) but not with
      treatment (p=0.87). Conclusions: Prostate cancer patients aligned with
      accountable care organizations had similar rates of treatment, but increased
      spending, in the year following diagnosis. These findings were similar across
      practice affiliations. Better specialist engagement by accountable care
      organizations may be necessary for them to alter practice patterns for specialty
      care.

PMID- 29170756
TI  - Healthy Hunger-Free Kids Act Increases Phytochemicals in Menus and Curriculum
      Furthers Identification of Phytochemical-Rich Foods.
AB  - Objective: This study evaluated whether providing the Fruits and Vegetables (F/V)
      required by the Healthy Hunger-Free Kids Act (HHFKA) increased
      phytochemical/antioxidant content of school lunches. Additionally, the ability of
      adolescents to apply their nutritional knowledge following participation in a
      nutrition-focused science-based curriculum was assessed. Methods: Changes in
      antioxidant/phytochemical content from F/V offered in school lunch menus were
      analyzed Pre-and Post-HHFKA. Food logs completed by 717 youth aged 10-18 were
      analyzed for correctly identifying "fighting foods". Results: Significant
      increases in antioxidant/phytochemical content resulted following implementation
      of HHFKA (P<0.05). Seventy-five percent [0, 100] of the time students accurately
      identified "fighting foods" in their one-day in-school food log (n=468).
      Conclusions and Implications: Creatively incorporating nutrition education into
      core curriculum, when paired with a supportive built environment that increases
      F/V access (HHFKA), generates a multilevel intervention promoting F/V consumption
      among school-aged youth.

PMID- 29170757
TI  - Human pluripotent stem cell-derived epicardial progenitors can differentiate to
      endocardial-like endothelial cells.
AB  - During heart development, epicardial progenitors contribute various cardiac
      lineages including smooth muscle cells, cardiac fibroblasts, and endothelial
      cells. However, their specific contribution to the human endothelium has not yet
      been resolved, at least in part due to the inability to expand and maintain human
      primary or pluripotent stem cell (hPSC)-derived epicardial cells. Here we first
      generated CDH5-2A-eGFP knock-in hPSC lines and differentiated them into self
      renewing WT1+ epicardial cells, which gave rise to endothelial cells upon VEGF
      treatment in vitro. In addition, we found that the percentage of endothelial
      cells correlated with WT1 expression in a WT1-2A-eGFP reporter line. The
      resulting endothelial cells displayed many endocardium-like endothelial cell
      properties, including high expression levels of endocardial-specific markers,
      nutrient transporters and well-organized tight junctions. These findings suggest
      that human epicardial progenitors may have the capacity to form endocardial
      endothelium during development and have implications for heart regeneration and
      cardiac tissue engineering.

PMID- 29170758
TI  - Design and Rationale for a Technology-based Healthy Lifestyle Intervention in
      Older Adults Grieving the Loss of a Spouse.
AB  - Introduction: Experiencing the death of a spouse during late life is associated
      with an increased risk of developing debilitating mental health problems. Healthy
      lifestyle practices, such as regular exercise, healthy eating, and good sleep
      hygiene are promising strategies to influence the mental health and associated
      physical symptoms of late-life spousal bereavement. Objective: This paper
      describes the design and rationale of an intervention development study
      addressing selective and indicated prevention of depression, anxiety, and/or
      complicated grief disorder(s) among adults 60 years and older who are grieving
      the recent loss (within 8 months) of a spouse or partner. Methods: In Phase I,
      now complete, we developed and standardized behavioral self-monitoring of daily
      lifestyle choices via an electronic diary (BSM) and the combined BSM +
      motivational interviewing-based lifestyle coaching (BSM+MI) to be administered to
      participants grieving the loss of loved one. In Phase II, we have been
      implementing the interventions in a randomized controlled trial and addressing
      challenges related to recruitment. Randomization is to one of three cells: BSM,
      BSM+MI, or an enhanced usual care condition. Discussion: Several challenges in
      implementing our lifestyle interventions to older widow(er)s who are at risk for
      common mental disorders have been identified. Direct outreach to hospice
      organizations is an effective way to identify older adults in the early months
      following spousal death. Results from study may advance the field of grief
      support and promote a healthy adaptation to widowhood.

PMID- 29170759
TI  - Autism, Attention, and Alpha Oscillations: An Electrophysiological Study of
      Attentional Capture.
AB  - Background: Autism spectrum disorder (ASD) is associated with deficits in
      adaptively orienting attention to behaviorally-relevant information. Neural
      oscillatory activity plays a key role in brain function and provides a high
      resolution temporal marker of attention dynamics. Alpha band (8-12 Hz) activity
      is associated with both selecting task-relevant stimuli and filtering task
      irrelevant information. Methods: The present study used electroencephalography
      (EEG) to examine alpha-band oscillatory activity associated with attentional
      capture in nineteen children with ASD and twenty-one age- and IQ-matched
      typically developing (TD) children. Participants completed a rapid serial visual
      presentation paradigm designed to investigate responses to behaviorally-relevant
      targets and contingent attention capture by task-irrelevant distractors, which
      either did or did not share a behaviorally-relevant feature. Participants also
      completed six minutes of eyes-open resting EEG. Results: In contrast to their TD
      peers, children with ASD did not evidence posterior alpha desynchronization to
      behaviorally-relevant targets. Additionally, reduced target-related
      desynchronization and poorer target detection were associated with increased ASD
      symptomatology. TD children also showed behavioral and electrophysiological
      evidence of contingent attention capture, whereas children with ASD showed no
      behavioral facilitation or alpha desynchronization to distractors that shared a
      task-relevant feature. Lastly, children with ASD had significantly decreased
      resting alpha power, and for all participants increased resting alpha levels were
      associated with greater task-related alpha desynchronization. Conclusions: These
      results suggest that in ASD under-responsivity and impairments in orienting to
      salient events within their environment are reflected by atypical EEG oscillatory
      neurodynamics, which may signify atypical arousal levels and/or an
      excitatory/inhibitory imbalance.

PMID- 29170760
TI  - The long reach of early adversity: Parenting, stress, and neural pathways to
      antisocial behavior in adulthood.
AB  - Background: Early life adversities including harsh parenting, maternal
      depression, neighborhood deprivation, and low family economic resources are more
      prevalent in low-income urban environments and are potent predictors of
      psychopathology, including, for boys, antisocial behavior (AB). However, little
      research has examined how these stressful experiences alter later neural
      function. Moreover, identifying genetic markers of greater susceptibility to
      adversity is critical to understanding biopsychosocial pathways from early
      adversity to later psychopathology. Methods: Within a sample of 310 low-income
      boys followed from age 1.5 to 20, multimethod assessments of adversities were
      examined at age 2 and age 12. At age 20, amygdala reactivity to emotional facial
      expressions was assessed using fMRI, and symptoms of Antisocial Personality
      Disorder were assessed via structured clinical interview. Genetic variability in
      cortisol signaling (CRHR1) was examined as a moderator of pathways to amygdala
      reactivity. Results: Observed parenting and neighborhood deprivation at age 2
      each uniquely predicted amygdala reactivity to emotional faces at age 20 over and
      above other adversities measured at multiple developmental periods. Harsher
      parenting and greater neighborhood deprivation in toddlerhood predicted
      clinically-significant symptoms of AB via less amygdala reactivity to fearful
      facial expressions and this pathway was moderated by genetic variation in CRHR1.
      Conclusions: These results elucidate a pathway linking early adversity to less
      amygdala reactivity to social signals of interpersonal distress 18 years later,
      which in turn increased risk for serious AB. Moreover, these findings suggest a
      genetic marker of youth more susceptible to adversity.

PMID- 29170761
TI  - IV Infiltration and Latex Allergy in an Infant: Early Recognition is Key to
      Prevent Lasting Disability.
AB  - Latex allergy confounded by IV infiltration presents a serious problem for
      pediatric patients. If unrecognized, it can lead to serious neurologic deficits,
      loss of limb mobility, compartment syndrome, and ultimately lasting disability.
      Appropriate early recognition can prevent progression to these devastating
      outcomes. In this case report, we present an infant with IV infiltration and
      latex allergy. The case is used to highlight important clinical diagnostic
      criteria, treatment approaches, and how to prevent detrimental outcomes. We
      provide a detailed review of the literature and highlight the key teaching points
      in a reader-friendly reference table.

PMID- 29170762
TI  - Clinical Utility of CLIA-Grade AR-V7 Testing in Patients With Metastatic
      Castration-Resistant Prostate Cancer.
AB  - Purpose: A splice variant of the androgen receptor, AR-V7, confers resistance to
      AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with
      metastatic castration-resistant prostate cancer. Since August 2015, a clinical
      grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells
      (CTCs) has been available to providers through a Clinical Laboratory Improvement
      Amendments-certified laboratory at Johns Hopkins University. Methods: We
      contacted ordering providers of the first 150 consecutive tests by using a
      questionnaire-based survey to determine how the results of AR-V7 testing were
      used to influence clinical practice. Results: In all, 142 (95%) of 150
      questionnaires were completed by 38 providers from 29 sites across the United
      States and Canada. AR-V7 test results were reported either as CTC- (28%), CTC+/AR
      V7- (30%), or CTC+/AR-V7+ (42%). Prevalence of AR-V7 detection increased with
      prior exposure to ATTs (abiraterone and enzalutamide naive, 22%; after
      abiraterone or enzalutamide, 35%; after abiraterone and enzalutamide, 43%).
      Overall, management was affected by AR-V7 testing in 53% of the patients and even
      more often with CTC+/AR-V7+ results. AR-V7+ patients were commonly switched from
      ATT to taxane chemotherapy (43%) or were offered a clinical trial (43%);
      management remained unchanged in only 14% of these patients. Overall, patients
      who had a change in management on the basis of AR-V7 testing were significantly
      more likely to achieve a physician-reported 50% decline in prostate-specific
      antigen response on next-line therapy than those who did not change treatment
      (54% v 31%; P = .015). Conclusion: Providers used AR-V7 testing to influence
      clinical decision making more often than not. Physicians reported thatmenwithAR
      V7+results had the most treatment changes, and such men were preferentially
      managed with taxane therapy or offered a clinical trial, which may have improved
      outcomes.

PMID- 29170763
TI  - GPU Acceleration of DSP for Communication Receivers.
AB  - Graphics processing unit (GPU) implementations of signal processing algorithms
      can outperform CPU-based implementations. This paper describes the GPU
      implementation of several algorithms encountered in a wide range of high-data
      rate communication receivers including filters, multirate filters, numerically
      controlled oscillators, and multi-stage digital down converters. These structures
      are tested by processing the 20 MHz wide FM radio band (88-108 MHz). Two receiver
      structures are explored: a single channel receiver and a filter bank channelizer.
      Both run in real time on NVIDIA GeForce GTX 1080 graphics card.

PMID- 29170764
TI  - Mortality Trajectories at Exceptionally High Ages: A Study of Supercentenarians.
AB  - The growing number of persons surviving to age 100 years and beyond raises
      questions about the shape of mortality trajectories at exceptionally high ages,
      and this problem may become significant for actuaries in the near future.
      However, such studies are scarce because of the difficulties in obtaining
      reliable age estimates at exceptionally high ages. The current view about
      mortality beyond age 110 years suggests that death rates do not grow with age and
      are virtually flat. The same assumption is made in the new actuarial VBT tables.
      In this paper, we test the hypothesis that the mortality of supercentenarians
      (persons living 110+ years) is constant and does not grow with age, and we
      analyze mortality trajectories at these exceptionally high ages. Death records of
      supercentenarians were taken from the International Database on Longevity (IDL).
      All ages of supercentenarians in the database were subjected to careful
      validation. We used IDL records for persons belonging to extinct birth cohorts
      (born before 1895) since the last deaths in IDL were observed in 2007. We also
      compared our results based on IDL data with a more contemporary database
      maintained by the Gerontology Research Group (GRG). First we attempted to
      replicate findings by Gampe (2010), who analyzed IDL data and came to the
      conclusion that "human mortality after age 110 is flat." We split IDL data into
      two groups: cohorts born before 1885 and cohorts born in 1885 and later. Hazard
      rate estimates were conducted using the standard procedure available in Stata
      software. We found that mortality in both groups grows with age, although in
      older cohorts, growth was slower compared with more recent cohorts and not
      statistically significant. Mortality analysis of more numerous 1884-1894 birth
      cohort with the Akaike goodness-of-fit criterion showed better fit for the
      Gompertz model than for the exponential model (flat mortality). Mortality
      analyses with GRG data produced similar results. The remaining life expectancy
      for the 1884-1894 birth cohort demonstrates rapid decline with age. This decline
      is similar to the computer-simulated trajectory expected for the Gompertz model,
      rather than the extremely slow decline in the case of the exponential model.
      These results demonstrate that hazard rates after age 110 years do not stay
      constant and suggest that mortality deceleration at older ages is not a universal
      phenomenon. These findings may represent a challenge to the existing theories of
      aging and longevity, which predict constant mortality in the late stages of life.
      One possibility for reconciliation of the observed phenomenon and the existing
      theoretical consideration is a possibility of mortality deceleration and
      mortality plateau at very high yet unobservable ages.

PMID- 29170765
TI  - Historical Evolution of Old-Age Mortality and New Approaches to Mortality
      Forecasting.
AB  - Knowledge of future mortality levels and trends is important for actuarial
      practice but poses a challenge to actuaries and demographers. The Lee-Carter
      method, currently used for mortality forecasting, is based on the assumption that
      the historical evolution of mortality at all age groups is driven by one factor
      only. This approach cannot capture an additive manner of mortality decline
      observed before the 1960s. To overcome the limitation of the one-factor model of
      mortality and to determine the true number of factors underlying mortality
      changes over time, we suggest a new approach to mortality analysis and
      forecasting based on the method of latent variable analysis. The basic assumption
      of this approach is that most variation in mortality rates over time is a
      manifestation of a small number of latent variables, variation in which gives
      rise to the observed mortality patterns. To extract major components of mortality
      variation, we apply factor analysis to mortality changes in developed countries
      over the period of 1900-2014. Factor analysis of time series of age-specific
      death rates in 12 developed countries (data taken from the Human Mortality
      Database) identified two factors capable of explaining almost 94 to 99 percent of
      the variance in the temporal changes of adult death rates at ages 25 to 85 years.
      Analysis of these two factors reveals that the first factor is a "young-age" or
      background factor with high factor loadings at ages 30 to 45 years. The second
      factor can be called an "oldage" or senescent factor because of high factor
      loadings at ages 65 to 85 years. It was found that the senescent factor was
      relatively stable in the past but now is rapidly declining for both men and
      women. The decline of the senescent factor is faster for men, although in most
      countries, it started almost 30 years later. Factor analysis of time series of
      age-specific death rates conducted for the oldest-old ages (65 to 100 years)
      found two factors explaining variation of mortality at extremely old ages in the
      United States. The first factor is comparable to the senescent factor found for
      adult mortality. The second factor, however, is specific to extreme old ages (96
      to 100 years) and shows peaks in 1960 and 2000. Although mortality below 90 to 95
      years shows a steady decline with time driven by the senescent factor, mortality
      of centenarians does not decline and remains relatively stable. The approach
      suggested in this paper has several advantages. First, it is able to determine
      the total number of independent factors affecting mortality changes over time.
      Second, this approach allows researchers to determine the time interval in which
      underlying factors remain stable or undergo rapid changes. Most methods of
      mortality projections are not able to identify the best base period for mortality
      projections, attempting to use the longest-possible time period instead. We
      observe that the senescent factor of mortality continues to decline, and this
      decline does not demonstrate any indications of slowing down. At the same time,
      mortality of centenarians does not decline and remains stable. The lack of
      mortality decline at extremely old ages may diminish anticipated longevity gains
      in the future.

PMID- 29170766
TI  - Process Monitoring in the Intensive Care Unit: Assessing Patient Mobility Through
      Activity Analysis with a Non-Invasive Mobility Sensor.
AB  - Throughout a patient's stay in the Intensive Care Unit (ICU), accurate
      measurement of patient mobility, as part of routine care, is helpful in
      understanding the harmful effects of bedrest [1]. However, mobility is typically
      measured through observation by a trained and dedicated observer, which is
      extremely limiting. In this work, we present a video-based automated mobility
      measurement system called NIMS: Non-Invasive Mobility Sensor . Our main
      contributions are: (1) a novel multi-person tracking methodology designed for
      complex environments with occlusion and pose variations, and (2) an application
      of human-activity attributes in a clinical setting. We demonstrate NIMS on data
      collected from an active patient room in an adult ICU and show a high inter-rater
      reliability using a weighted Kappa statistic of 0.86 for automatic prediction of
      the highest level of patient mobility as compared to clinical experts.

PMID- 29170767
TI  - Robust indirect band gap and anisotropy of optical absorption in B-doped
      phosphorene.
AB  - A traditional doping technique plays an important role in the band structure
      engineering of two-dimensional nanostructures. Since electron interaction is
      changed by doping, the optical and electrochemical properties could also be
      significantly tuned. In this study, density functional theory calculations have
      been employed to explore the structural stability, and electronic and optical
      properties of B-doped phosphorene. The results show that all B-doped phosphorenes
      are stable with a relatively low binding energy. Of particular interest is that
      these B-doped systems exhibit an indirect band gap, which is distinct from the
      direct one of pure phosphorene. Despite the different concentrations and
      configurations of B dopants, such indirect band gaps are robust. The screened
      hybrid density functional HSE06 predicts that the band gap of B-doped phosphorene
      is slightly smaller than that of pure phosphorene. Spatial charge distributions
      at the valence band maximum (VBM) and the conduction band minimum (CBM) are
      analyzed to understand the features of an indirect band gap. By comparison with
      pure phosphorene, B-doped phosphorenes exhibit strong anisotropy and intensity of
      optical absorption. Moreover, B dopants could enhance the stability of Li
      adsorption on phosphorene with less sacrifice of the Li diffusion rate. Our
      results suggest that B-doping is an effective way of tuning the band gap,
      enhancing the intensity of optical absorption and improving the performances of
      Li adsorption, which could promote potential applications in novel optical
      devices and lithium-ion batteries.

PMID- 29170768
TI  - Counterion effects on the ultrafast dynamics of charge-transfer-to-solvent
      electrons.
AB  - We performed femtosecond transient absorption (TA) experiments to monitor the
      solvation dynamics of charge-transfer-to-solvent (CTTS) electrons originating
      from UV photoexcitation of ammoniated iodide in close proximity to the
      counterions. Solutions of KI were prepared in liquid ammonia and TA experiments
      were carried out at different temperatures and densities, along the liquid-gas
      coexistence curve of the fluid. The results complement previous femtosecond TA
      work by P. Vohringer's group in neat ammonia via multiphoton ionization. The
      dynamics of CTTS-detached electrons in ammonia was found to be strongly affected
      by ion pairing. Geminate recombination time constants as well as escape
      probabilities were determined from the measured temporal profiles and analysed as
      a function of the medium density. A fast unresolved (tau < 250 fs) increase of
      absorption related to the creation/thermalization of solvated electron species
      was followed by two decay components: one with a characteristic time around 10
      ps, and a slower one that remains active for hundreds of picoseconds. While the
      first process is attributed to an early recombination of (I, e-) pairs, the
      second decay and its asymptote reflects the effect of the K+ counterion on the
      geminate recombination dynamics, rate and yield. The cation basically acts as an
      electron anchor that restricts the ejection distance, leading to solvent
      separated counterion-electron species. The formation of (K+, NH3, e-) pairs close
      to the parent iodine atom brings the electron escape probability to very low
      values. Transient spectra of the electron species have also been estimated as a
      function of time by probing the temporal profiles at different wavelengths.

PMID- 29170769
TI  - Design and self-assembly of PBLG-b-ELP hybrid diblock copolymers based on
      synthetic and elastin-like polypeptides.
AB  - The precision synthesis and self-assembly of amphiphilic copolypeptides
      containing a recombinant elastin-like polypeptide (ELP) block used as a
      macroinitiator for the ring opening polymerization (ROP) of gamma-benzyl-l
      glutamate (gamma-BLG NCA) are herein presented. The molecular weight of the
      resulting PBLG-b-ELP block copolypeptides was precisely controlled without the
      use of complex initiator or demanding experimental setup. Diblock copolypeptides
      were obtained with an excellent control of the polymerization highlighted by the
      dispersity below 1.04. These amphiphilic hybrid synthetic/recombinant
      copolypeptides were self-assembled in water and the nanoparticles obtained were
      characterized by a combination of dynamic light scattering and electron
      microscopy. A variety of morphologies, namely polymersomes, inter-connected worm
      like micelles and spherical micelles, were evidenced depending on the hydrophilic
      ratio of the diblocks as well as the self-assembly procedure.

PMID- 29170770
TI  - Azobenzene photoisomerization quantum yields in methanol redetermined.
AB  - The quantum yields of azobenzene photoisomerization in methanol solution were
      redetermined using newly obtained molar absorption coefficients of its cis- and
      trans-isomers. The results differ substantially from those published previously,
      especially in the range of the npi* absorption band. Besides actinometry, these
      findings are relevant for applications of azobenzene derivatives in optical
      switching.

PMID- 29170772
TI  - A kinetic study of the gas-phase reactions of 1-methylsilacyclobutane in hot wire
      chemical vapor deposition.
AB  - The reaction kinetics of the decomposition of 1-methylsilacyclobutane (MSCB) in a
      hot wire chemical vapor deposition (HWCVD) reactor was investigated. The stable
      reaction products were monitored using vacuum ultraviolet laser single photon
      ionization in tandem with time-of-flight mass spectrometry. Steady-state
      approximation was used to determine the rate constants of three individual
      decomposition pathways of MSCB, i.e., cycloreversion to form ethene and
      methylsilene (R1), ring opening to form propene and methylsilylene (R2), and
      exocyclic Si-CH3 bond cleavage to form CH3 radicals (R3). The activation energies
      (Ea) for R2 and R3 in a HWCVD reactor were determined to be 86.6 kJ mol-1 and 106
      kJ mol-1, respectively. The fact that these Ea values are close to those obtained
      for the MSCB decomposition on metal surfaces under collision-free conditions
      indicates that the heterogeneous reactions on the hot wire surface govern the gas
      phase reaction kinetics in the HWCVD reactor. In addition, the Ea values obtained
      from a theoretical study of the decomposition kinetics using ab initio
      calculations at the CCSD(T)/6-311++G(3d,2p)//MP2/6-311++G(d,p) level were 62.9
      kcal mol-1 (i.e., 263 kJ mol-1), 62.0 kcal mol-1 (i.e., 259 kJ mol-1), and 86.2
      kcal mol-1 (i.e., 361 kJ mol-1) for R1, R2, and R3, respectively. The much lower
      experimental Ea values compared with those from the theoretical calculations
      clearly suggest that the tungsten filament in the HWCVD reactor catalyzed the
      decomposition.

PMID- 29170771
TI  - A fluorescent combinatorial logic gate with Na+, H+-enabled OR and H+-driven low
      medium-high ternary logic functions.
AB  - A novel fluorescent molecular logic gate with a 'fluorophore-spacer1-receptor1
      spacer2-receptor2' format is demonstrated in 1 : 1 (v/v) methanol/water. The
      molecule consists of an anthracene fluorophore, and tertiary alkyl amine and N-(2
      methoxyphenyl)aza-15-crown-5 ether receptors. In the presence of threshold
      concentrations of H+ and Na+, the molecule switches 'on' as an AND logic gate
      with a fluorescence quantum yield of 0.21 with proton and sodium binding
      constants of log betaH+ = 9.0 and log betaNa+ = 3.2, respectively. At higher
      proton levels, protonation also occurs at the anilinic nitrogen atom ether with a
      log betaH+ = 4.2, which allows for Na+, H+-enabled OR (OR + AND circuit) and H+
      driven ternary logic functions. The reported molecule is compared and contrasted
      to classic anthracene-based Na+ and H+ logic gates. We propose that such logic
      based molecules could be useful tools for probing the vicinity of Na+, H+
      antiporters in biological systems.

PMID- 29170773
TI  - Solvatochromism in perylene diimides; experiment and theory.
AB  - We report an experimental and computational investigation into the
      solvatochromism of a perylene diimide derivative. The alkyl swallowtail
      substituents allowed solubility in many solvents of widely differing polarity,
      with a complicated resultant behaviour, illustrating both negative and positive
      solvatochromism as a function of dielectric constant. Luminescence quantum yield
      and optical absorption linewidth displayed an inverse correlation, indicating
      varying degrees of intermolecular aggregation, and a remarkably similar trend was
      found between the peak absorption wavelength and the solvent boiling point,
      illustrating the dependency of aggregation on the solvent interactions. These
      outline trends may be parameterised by an empirically derived dimensionless
      quantity, as a tool to be used in more sophisticated future models of
      solvatochromism in small molecule chromophores.

PMID- 29170774
TI  - A modular approach towards functionalized highly stable self-complementary
      quadruple hydrogen bonded systems.
AB  - Self-complementary quadruple hydrogen bonded systems have shown potential as key
      building blocks for developing various supramolecular polymers. Opportunities for
      the introduction of multiple functionalities would further augment, in principle,
      their application potential. Herein, we report a novel modular approach to
      simultaneously introduce two closely aligned side chains into AADD-type self
      complementary quadruple hydrogen-bonding systems. Dithiane-tethered
      ureidopyrimidinone has been used as a reactive intermediate to efficiently attach
      closely aligned side chains by simply reacting with amines to form highly stable
      molecular duplexes. These duplexes featuring AADD-type arrays of hydrogen bonding
      codes are highly stable in non-polar solvents (Kdim > 1.9 * 107 M-1 in CDCl3) as
      well as in polar solvents (Kdim > 105 in 10% DMSO-d6/CDCl3). Another notable
      feature of these self-assembling systems is their insensitivity to prototropy
      related issues owing to their prototropic degeneracy, which will enhance their
      application potential in supramolecular chemistry.

PMID- 29170775
TI  - Rhodium-catalyzed benzoisothiazole synthesis by tandem annulation reactions of
      sulfoximines and activated olefins.
AB  - Rhodium(iii)-catalyzed N-directed ortho C-H activation reactions have been
      developed for the synthesis of unique heterocyclic benzoisothiazoles. Herein,
      this novel tandem annulation approach can efficiently construct benzoisothiazole
      compounds from free NH-sulfoximines and alkenes via C-H activation, olefination
      and subsequent intramolecular aza-Michael cyclization.

PMID- 29170776
TI  - Fe-Catalyzed radical-type difunctionalization of styrenes with aliphatic
      aldehydes and trimethylsilyl azide via a decarbonylative alkylation-azidation
      cascade.
AB  - A convenient Fe-catalyzed decarbonylative alkylation-azidation cascade reaction
      of styrene derivatives with aliphatic aldehydes and TMSN3 to provide aliphatic
      azides is developed. With DTBP as an oxidant and radical initiator, this reaction
      smoothly converts aliphatic aldehydes into 1 degrees , 2 degrees  and 3 degrees 
      alkyl radicals and subsequently allows for the cascade construction of C(sp3)
      C(sp3) and C(sp3)-N bonds via radical insertion and nucleophilic azidation.

PMID- 29170777
TI  - Radical fluorination reactions by thermal and photoinduced methods.
AB  - The radical or radical ion-based fluorination reactions of organic compounds will
      be presented. These methodologies include fluorination processes accomplished
      through thermal or photoinduced radical/electron transfer methods. In doing so,
      the fluorination reactions of diverse families of organic compounds such as
      aliphatic and aromatic substrates will be presented. Recently summarized or
      reviewed articles will be mentioned but not discussed.

PMID- 29170778
TI  - [18F]ODIBO: a prosthetic group for bioorthogonal radiolabeling of macromolecules
      via strain-promoted alkyne-azide cycloaddition.
AB  - A novel prosthetic group for the efficient radiolabeling of macromolecules has
      been developed. [18F]oxadibenzocyclooctyne ([18F]ODIBO) is synthesized in high
      radiochemical yield and applied for nearly quantitative conjugation to azide
      tagged peptides and proteins at room temperature and low substrate
      concentrations. The resulting bioconjugates are chemically and radiochemically
      pure and free of toxic solvents and catalysts.

PMID- 29170779
TI  - Deliberate modification of the solid electrolyte interphase (SEI) during
      lithiation of magnetite, Fe3O4: impact on electrochemistry.
AB  - Magnetite is a conversion anode material displaying multi-electron transfer
      during lithiation and delithiation. The solid electrolyte interphase (SEI) on
      magnetite, Fe3O4, electrodes for lithium ion batteries was deliberately modified
      through the use of fluoroethylene carbonate (FEC) electrolyte additive, improving
      both capacity retention and rate capability. Analysis showed reduction of FEC at
      higher voltage compared to non-fluorinated solvents with formation of a modified
      lithium flouride containing electrode surface.

PMID- 29170780
TI  - The absorption spectrum of cis-azobenzene.
AB  - Azobenzene is a prototypical photochromic molecule existing in two isomeric
      forms, which has numerous photochemical applications that rely on a precise
      knowledge of the molar absorption coefficients (epsilon). Careful analysis
      revealed that the previously reported absorption spectra of the "pure" isomers
      were in fact mutually contaminated by small amounts of the other isomer.
      Therefore, the absorption spectra of both trans- and cis-azobenzene in methanol
      were re-determined at temperatures of 5-45  degrees C. The thermodynamically more
      stable trans-azobenzene was prepared by warming the solution in the dark. To
      obtain the spectrum of cis-azobenzene three methods were used, which gave
      consistent results within the limits of error. The method based on the
      subtraction of derivative spectra coupled with a global analysis of the spectra
      recorded during thermal cis-trans isomerization is shown to give slightly more
      reliable results than the method using isomeric ratios determined by 1H-NMR. The
      described methods are readily generalizable to other azobenzene derivatives and
      to other photochromic systems. The practical implication of the re-determined
      epsilon values is demonstrated by a very high precision of spectrophotometric
      species analysis in azobenzene isomeric mixtures. The new epsilon values imply
      that the previously reported quantum yields must be revised.

PMID- 29170781
TI  - Structure-reactivity correlations of the abnormal Beckmann reaction of
      dihydrolevoglucosenone oxime.
AB  - A structural, spectroscopic and computational study of a series of oximes was
      undertaken to investigate how geometric and structural changes relevant to the
      reaction coordinate for the Beckmann reaction (normal Beckmann) and Beckmann
      fragmentation (abnormal Beckmann) manifest in the ground state. X-ray structures
      of a range of oximes derived from dihydrolevoglucosan (CyreneTM; which undergoes
      the abnormal Beckmann reaction), in which the oxygen substituent was
      systematically varied were determined. As the electron demand of the OR group
      increased, the major structural changes included lengthening of the N-OR bond
      distance, and a decrease in the magnitude of the C2[double bond, length as m
      dash]N-O bond angle, consistent with the changes seen for cyclohexanone oximes,
      which undergo the normal Beckmann reaction. However, unique to the Cyrene oximes,
      an increase in the length of the fissile C1-C2 bond was observed, which
      correlated with a decrease in the 13C-13C 1-bond coupling constants as the
      electron demand of the OR substituent increased. Computational studies of Cyrene
      and cyclohexanone oximes using Natural Bond Orbital analysis support an
      electronic structure involving n(O) -> sigma*C1-C2 and sigmaC1-C2 -> sigma*N-O
      localized orbital interactions.

PMID- 29170782
TI  - Coordination-driven assembly of catechol-modified chitosan for the kidney
      specific delivery of salvianolic acid B to treat renal fibrosis.
AB  - Kidney-specific delivery is critically important for the treatment of renal
      fibrosis with drugs such as salvianolic acid B (Sal B). Here we report a kidney
      specific nanocomplex formed by the coordination-driven assembly of catechol
      modified low molecular weight chitosan (HCA-Chi), calcium ions and Sal B. The
      prepared HCA-Chi-Ca-Sal B (HChi-Ca-Sal B) nanocomplex reversed the TGF-beta1
      induced epithelial-mesenchymal transition (EMT) in HK-2 cells. In vivo imaging
      demonstrated a kidney-specific biodistribution of the nanocomplex. The anti
      fibrosis effect of HChi-Ca-Sal B was tested in a mouse model of unilateral
      ureteral obstruction (UUO). Significant attenuation of the morphological lesions
      and the levels of extracellular matrix (ECM) proteins in the tubulointerstitium
      was observed in mice treated with HChi-Ca-Sal B, suggesting that the nanocomplex
      was able to prevent fibrosis better than the treatment with free Sal B. It was
      concluded that the HChi-Ca-Sal B nanocomplex showed a specific renal targeting
      capacity and could be utilized to enhance Sal B delivery for treating renal
      fibrosis.

PMID- 29170783
TI  - Structure-activity relationships for ruthenium and osmium anticancer agents -
      towards clinical development.
AB  - Anticancer metallodrugs based on ruthenium and osmium are among the most
      investigated and advanced non-platinum metallodrugs. Inorganic drug discovery
      with these agents has undergone considerable advances over the past two decades
      and has currently two representatives in active clinical trials. As many
      ruthenium and osmium metallodrugs are prodrugs, a key question to be addressed is
      how the molecular reactivity of such metal-based therapeutics dictates the
      selectivity and the type of interaction with molecular targets. Within this
      frame, this review introduces the field by the examples of the most advanced
      ruthenium lead structures. Then, global structure-activity relationships are
      discussed for ruthenium and osmium metallodrugs with respect to in vitro
      antiproliferative/cytotoxic activity and in vivo tumor-inhibiting properties, as
      well as pharmacokinetics. Determining and validating global mechanisms of action
      and molecular targets are still major current challenges. Moreover, significant
      efforts must be invested in screening in vivo tumor models that mimic human
      pathophysiology to increase the predictability for successful preclinical and
      clinical development of ruthenium and osmium metallodrugs.

PMID- 29170784
TI  - A wheel-shaped Dy(iii) single-molecule magnet supported by polyoxotungstates.
AB  - A wheel-shaped Dy(iii) single-molecule magnet (SMM), supported by
      polyoxotungstates, Cs15K8Na12[K?{(AsW9O33)Dy(H2O)2}6].71H2O (1), is described
      here. The polyanion of 1 possesses an idealized S6 symmetry. The effective energy
      barrier (68 K) obtained from magnetic studies is consistent with the
      deconvolution of the luminescence spectra of 1.

PMID- 29170785
TI  - Amplification or cancellation of Fano resonance and quantum confinement induced
      asymmetries in Raman line-shapes.
AB  - Fano resonance is reported here to be playing a dual role by amplifying or
      compensating for the quantum confinement effect induced asymmetry in Raman line
      shape in silicon (Si) nanowires (NWs) obtained from heavily doped n- and p-type
      Si wafers respectively. The compensatory nature results in a near symmetric Raman
      line-shape from heavily doped p-type Si nanowires (NWs) as both the components
      almost cancel each other. On the other hand, the expected asymmetry, rather with
      enhancement, has been observed from heavily doped n-type SiNWs. Such a system (p-
      & n-) dependent Raman line-shape study has been carried out by theoretical line
      shape analysis followed by experimental validation through suitably designed
      experiments. A dual role of Fano resonance in n- and p-type nano systems has been
      observed to modulate Raman spectra differently and reconcile accordingly to
      enhance and cease the Raman spectral asymmetry respectively. The present analysis
      will enable one to be more careful while analyzing a symmetric Raman line-shape
      from semiconductor nanostructures.

PMID- 29170787
TI  - Synthesis, computational, and spectroscopic analysis of tunable highly
      fluorescent BN-1,2-azaborine derivatives containing the N-BOH moiety.
AB  - Nine new polycyclic aromatic BN-1,2-azaborine analogues containing the N-BOH
      moiety were synthesized using a convenient two-step, one-pot procedure.
      Characterization of the prepared compounds show the luminescence wavelength and
      the quantum yields of the azaborines were tunable by controlling the power and
      location of the donor and acceptor substituents on the chromophore. UV-visible
      spectroscopy and density functional theory (DFT) computations revealed that the
      addition of electron-donating moieties to the isoindolinone hemisphere raised the
      energy of the HOMO, resulting in the reduction of the HOMO-LUMO gap. The addition
      of an electron-accepting moiety to the isoindolinone hemisphere and an electron
      donating group to the boronic acid hemisphere decreased the HOMO-LUMO gap
      considerably, leading to emission properties from partial intramolecular charge
      transfer (ICT) states. The combined effect of an acceptor on the isoindolinone
      side and a donor on the boronic acid side (strong acceptor-pi-donor) gave the
      most red-shifted absorption. The polycyclic aromatic BN-1,2-azaborines emitted
      strong fluorescence in solution and in the solid-state with the largest red
      shifted emission at 640 nm and a Stokes shift of Deltalambda = 218 nm, or Deltanu
      = 8070 cm-1.

PMID- 29170788
TI  - [Incontinence after radical prostatectomy : Male Sling or "best option" first?]
AB  - Postprostatectomy incontinence (PPI) is a rare complication of radical
      prostatectomy, and it may lead to severe limitations for the patient and loss of
      quality of life. Several different surgical options for the therapy of PPI are
      available and may be chosen depending on severity of incontinence, residual
      urethral sphincter function, and previous history of radiotherapy. Alternatives
      to artificial urinary sphincters which over the last few decades have represented
      the gold standard for treatment of PPI are fixed slings and adjustable devices.
      In cases of mild or moderate incontinence, male slings can be used. Adjustable
      devices can also be adopted in irradiated patient with good results. Artificial
      urinary sphincters represent the ideal option in case of severe incontinence.
      Absolute contraindications for the implant of this device are impaired dexterity
      and cognitive capacity of the patients that may make use of the pump difficult.
      One type of therapy for all patients does not exist and must be individually
      determined. It is influenced by the grade of incontinence, the anatomical
      conditions, and the patient's expectations. Thus, appropriate counselling is
      mandatory. A common opinion is that these devices are direct competitors in the
      treatment of PPI. In reality, these devices are completely different surgical
      methods that rely on different principles and therefore have different
      indications.

PMID- 29170786
TI  - Recent advances in the use of microfluidic technologies for single cell analysis.
AB  - The inherent heterogeneity in cell populations has become of great interest and
      importance as analytical techniques have improved over the past decades. With the
      advent of personalized medicine, understanding the impact of this heterogeneity
      has become an important challenge for the research community. Many different
      microfluidic approaches with varying levels of throughput and resolution exist to
      study single cell activity. In this review, we take a broad view of the recent
      microfluidic developments in single cell analysis based on microwell,
      microchamber, and droplet platforms. We cover physical, chemical, and molecular
      biology approaches for cellular and molecular analysis including newly emerging
      genome-wide analysis.

PMID- 29170791
TI  - Trauma-induced coagulopathy upon emergency room arrival: still a significant
      problem despite increased awareness and management?
AB  - PURPOSE: Over the last decade, the pivotal role of trauma-induced coagulopathy
      has been described and principal drivers have been identified. We hypothesized
      that the increased knowledge on coagulopathy of trauma would translate into a
      more cautious treatment, and therefore, into a reduced overall incidence rate of
      coagulopathy upon ER admission. PATIENTS AND METHODS: Between 2002 and 2013,
      61,212 trauma patients derived from the TraumaRegister DGU(r) had a full record
      of coagulation parameters and were assessed for the presence of coagulopathy.
      Coagulopathy was defined by a Quick's value < 70% and/or platelet counts <
      100,000/ul upon ER admission. For each year, the incidence of coagulopathy, the
      amount of pre-hospital administered i.v.-fluids and transfusion requirements were
      assessed. RESULTS: Coagulopathy upon ER admission was present in 24.5% of all
      trauma patients. Within the years 2002-2013, the annual incidence of coagulopathy
      decreased from 35 to 20%. Even in most severely injured patients (ISS > 50), the
      incidence of coagulopathy was reduced by 7%. Regardless of the injury severity,
      the amount of pre-hospital i.v.-fluids declined during the observed period by
      51%. Simultaneously, morbidity and mortality of severely injured patients were on
      the decrease. CONCLUSION: During the 12 years observed, a substantial decline of
      coagulopathy has been observed. This was paralleled by a significant decrease of
      i.v.-fluids administered in the pre-hospital treatment. The reduced presence of
      coagulopathy translated into decreased transfusion requirements and mortality.
      Nevertheless, especially in the most severely injured patients, posttraumatic
      coagulopathy remains a frequent and life-threatening syndrome.

PMID- 29170790
TI  - A multiple near isogenic line (multi-NIL) RNA-seq approach to identify candidate
      genes underpinning QTL.
AB  - KEY MESSAGE: This study demonstrates how identification of genes underpinning
      disease-resistance QTL based on differential expression and SNPs can be improved
      by performing transcriptomic analysis on multiple near isogenic lines.
      Transcriptomic analysis has been widely used to understand the genetic basis of a
      trait of interest by comparing genotypes with contrasting phenotypes. However,
      these approaches identify such large sets of differentially expressed genes that
      it proves difficult to isolate which genes underpin the phenotype of interest.
      This study tests whether using multiple near isogenic lines (NILs) can improve
      the resolution of RNA-seq-based approaches to identify genes underpinning disease
      resistance QTL. A set of NILs for a major effect Fusarium crown rot-resistance
      QTL in barley on the 4HL chromosome arm were analysed under Fusarium crown rot
      using RNA-seq. Differential gene expression and single nucleotide polymorphism
      detection analyses reduced the number of putative candidates from thousands
      within individual NIL pairs to only one hundred and two genes, which were
      differentially expressed or contained SNPs in common across NIL pairs and
      occurred on 4HL. Our findings support the value of performing RNA-seq analysis
      using multiple NILs to remove genetic background effects. The enrichment analyses
      indicated conserved differences in the response to infection between resistant
      and sensitive isolines suggesting that sensitive isolines are impaired in
      systemic defence response to Fusarium pseudograminearum.

PMID- 29170789
TI  - CREBBP and p300 lysine acetyl transferases in the DNA damage response.
AB  - The CREB-binding protein (CREBBP, or in short CBP) and p300 are lysine (K) acetyl
      transferases (KAT) belonging to the KAT3 family of proteins known to modify
      histones, as well as non-histone proteins, thereby regulating chromatin
      accessibility and transcription. Previous studies have indicated a tumor
      suppressor function for these enzymes. Recently, they have been found to
      acetylate key factors involved in DNA replication, and in different DNA repair
      processes, such as base excision repair, nucleotide excision repair, and non
      homologous end joining. The growing list of CBP/p300 substrates now includes
      factors involved in DNA damage signaling, and in other pathways of the DNA damage
      response (DDR). This review will focus on the role of CBP and p300 in the
      acetylation of DDR proteins, and will discuss how this post-translational
      modification influences their functions at different levels, including catalytic
      activity, DNA binding, nuclear localization, and protein turnover. In addition,
      we will exemplify how these functions may be necessary to efficiently coordinate
      the spatio-temporal response to DNA damage. CBP and p300 may contribute to genome
      stability by fine-tuning the functions of DNA damage signaling and DNA repair
      factors, thereby expanding their role as tumor suppressors.

PMID- 29170792
TI  - Prospective comparison among three intrarectal anesthetic treatments combined
      with periprostatic nerve block during transrectal ultrasonography-guided prostate
      biopsy.
AB  - BACKGROUND: Recent trends in prostate biopsy analgesia suggest a combination
      anesthetic to provide better pain relief than periprostatic nerve block (PPNB)
      alone. This study aimed to demonstrate the efficacy and safety of three
      intrarectal local anesthesia (IRLA) combined with PPNB in patients undergoing
      transrectal ultrasonography (TRUS)-guided prostate biopsy. METHODS: In this
      prospective, randomized study, 120 prostate biopsy patients were equally divided
      into four IRLA groups: group 1 (placebo) received simple lubrication; group 2
      received 2% lidocaine gel; group 3 received 100 mg indomethacin suppository and
      group 4 received 5% prilocaine/lidocaine (EMLA) cream. PPNB with 2% lidocaine was
      applied in all groups. A ten-point visual analog scale evaluated both pain
      associated with the probe insertion and pain associated with prostate sampling.
      Adverse effects or complications due to anesthesia during and after the procedure
      were documented. RESULTS: Compared with group 1, groups 3 and 4 had significantly
      lower pain scores at both probe insertion and prostate sampling while group 2
      showed no significant differences at both pain scores. Moreover, group 4 showed
      significantly lower pain scores at probe insertion compared to group 3, while no
      significant difference was observed at prostate sampling. Mild complications were
      observed in all groups with no significant difference in the incidence of
      complications between groups. CONCLUSION: Intrarectal application of EMLA cream
      is a more efficient pain reduction than either 2% lidocaine gel or 100 mg
      indomethacin suppository when applied combined with PPNB. This combination
      represents an effective option of pain relief for patients undergoing TRUS-guided
      prostate biopsy.

PMID- 29170793
TI  - Clinical predictors and risk factors for vaginal mesh extrusion.
AB  - PURPOSES: Our study aims to enhance the accuracy of the clinical diagnosis in
      patients with vaginal mesh extrusion following transvaginal mesh placement for
      pelvic organ prolapse using significant clinical parameters and risk factors.
      METHODS: All patients who underwent vaginal mesh removal were retrospectively
      reviewed from January 2000 to May 2014. Eligible patients were divided into two
      groups according to the presence of vaginal mesh extrusion. RESULTS: A total of
      862 patients, 798 were included. 357 (44.7%) had evidence of vaginal mesh
      extrusion, and 441 (55.3%) had no evidence of vaginal mesh extrusion. The mean
      age of the vaginal mesh extrusion group was slightly higher than in the group
      without vaginal mesh extrusion (58.7 +/- 11.2 vs. 56.4 +/- 11.5, respectively; p
      = 0.002). From multivariate analysis, the significant clinical correlations for
      vaginal mesh extrusion were vaginal bleeding [60 (16.9) vs. 14 (3.2%), p <
      0.001], hispareunia [48 (13.5) vs. 15 (3.4%), OR = 4.163, p < 0.001], and vaginal
      discharge [45 (12.6) vs. 18 (4.1%), p = 0.001]. The risk factors were multiple
      mesh implantations [218 (67.06) vs. 175 (39.68%), p < 0.001] and menopause [314
      (88) vs. 364 (82.7%), p = 0.145]. Demographic data, including BMI, sexual
      activity, vaginal atrophy, both local and systemic hormonal use, smoking status,
      and hysterectomy status, were not significantly different, as well as the
      clinical symptoms including dyspareunia, vaginal infection, and symptomatic
      vaginal bulge. CONCLUSIONS: Vaginal bleeding, hispareunia, and vaginal discharge
      were the most significant clinical predictors for raising suspicion of vaginal
      mesh extrusion. Multiple mesh implantations were a significant risk factor for
      extrusion.

PMID- 29170794
TI  - Three-dimensional microCT imaging of murine embryonic development from immediate
      post-implantation to organogenesis: application for phenotyping analysis of early
      embryonic lethality in mutant animals.
AB  - In this work, we applied three-dimensional microCT imaging to study murine
      embryogenesis in the range from immediate post-implantation period (embryonic day
      5.5) to mid-gestation (embryonic day 12.5) with the resolution up to 1.4
      um/voxel. Also, we introduce an imaging procedure for non-invasive volumetric
      estimation of an entire litter of embryos within the maternal uterine structures.
      This method allows for an accurate, detailed and systematic morphometric analysis
      of both embryonic and extra-embryonic components during embryogenesis. Three
      dimensional imaging of unperturbed embryos was performed to visualize the egg
      cylinder, primitive streak, gastrulation and early organogenesis stages of murine
      development in the C57Bl6/N mouse reference strain. Further, we applied our
      microCT imaging protocol to determine the earliest point when embryonic
      development is arrested in a mouse line with knockout for tRNA splicing
      endonuclease subunit Tsen54 gene. Our analysis determined that the embryonic
      development in Tsen54 null embryos does not proceed beyond implantation. We
      demonstrated that application of microCT imaging to entire litter of non
      perturbed embryos greatly facilitate studies to unravel gene function during
      early embryogenesis and to determine the precise point at which embryonic
      development is arrested in mutant animals. The described method is inexpensive,
      does not require lengthy embryos dissection and can be applicable for detailed
      analysis of mutant mice at laboratory scale as well as for high-throughput
      projects.

PMID- 29170795
TI  - Warfarin resistance from primidone in patient with essential tremor.

PMID- 29170796
TI  - Factors Affecting Element Concentrations in Eggshells of Three Sympatrically
      Nesting Waterbirds in Northern Poland.
AB  - Avian eggshells are convenient samples in biomonitoring studies, because they are
      easily accessible, especially from colonially or semicolonially breeding birds.
      In the present study, concentrations of 17 elements, including heavy metals and
      essential elements in post-hatch eggshells, were compared among three species of
      waterbirds of differing strategies for gaining reserves for egg production and
      diet: mallard, Anas platyrhynchos (ML, a capital breeder, mainly herbivorous),
      common tern, Sterna hirundo (CT, an income breeder, piscivorous) and black-headed
      gull, Chroicocephalus ridibundus (BHG, mixed strategy, omnivorous) and breeding
      sympatrically in three sites in North Poland. Analyses revealed that Fe, Zn, and
      Cu levels differed the most in the studied species, which may be explained by
      various contributions of fish, aquatic plants, and soil invertebrates in their
      diets. Generally, the studied species' eggshells accumulated amounts of elements
      comparable to those reported for other waterbirds without putting the growth and
      development of the embryo at risk. The only exception was very high levels of Cr
      in ML and CT, which may be explained by their foraging on aquatic organisms in
      waterbodies polluted by this element. Intersite differences in eggshell
      concentrations of Ni, Sr, Hg and Cr in CT (an income breeder) may be explained by
      the influence of local pollution sources (small factories, polluted river).

PMID- 29170797
TI  - Hydrophilic magnetic ionic liquid for magnetic headspace single-drop
      microextraction of chlorobenzenes prior to thermal desorption-gas chromatography
      mass spectrometry.
AB  - A new, fast, easy to handle, and environmentally friendly magnetic headspace
      single-drop microextraction (Mag-HS-SDME) based on a magnetic ionic liquid (MIL)
      as an extractant solvent is presented. A small drop of the MIL 1-ethyl-3
      methylimidazolium tetraisothiocyanatocobaltate(II) ([Emim]2[Co(NCS)4]) is located
      on one end of a small neodymium magnet to extract nine chlorobenzenes (1,2
      dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene, 1,2,3
      trichlorobenzene, 1,2,4-trichlorobenzene, 1,3,5-trichlorobenzene, 1,2,3,4
      tetrachlorobenzene, 1,2,4,5-tetrachlorobenzene, and pentachlorobenzene) as model
      analytes from water samples prior to thermal desorption-gas chromatography-mass
      spectrometry determination. A multivariate optimization strategy was employed to
      optimize experimental parameters affecting Mag-HS-SDME. The method was evaluated
      under optimized extraction conditions (i.e., sample volume, 20 mL; MIL volume, 1
      MUL; extraction time, 10 min; stirring speed, 1500 rpm; and ionic strength, 15%
      NaCl (w/v)), obtaining a linear response from 0.05 to 5 MUg L-1 for all analytes.
      The repeatability of the proposed method was evaluated at 0.7 and 3 MUg L-1
      spiking levels and coefficients of variation ranged between 3 and 18% (n = 3).
      Limits of detection were in the order of nanograms per liter ranging from 4 ng L
      1 for 1,4-dichlorobenzene and 1,2,3,4-tetrachlorobenzene to 8 ng L-1 for 1,2,4,5
      tetrachlorobenzene. Finally, tap water, pond water, and wastewater were selected
      as real water samples to assess the applicability of the method. Relative
      recoveries varied between 82 and 114% showing negligible matrix effects.
      Graphical abstract Magnetic headspace single-drop microextraction followed by
      thermal desorption-gas chromatography-mass spectrometry.

PMID- 29170798
TI  - Anatomical Road Mapping Using CT and MR Enterography for Ultrasound Molecular
      Imaging of Small Bowel Inflammation in Swine.
AB  - OBJECTIVES: To evaluate the feasibility and time saving of fusing CT and MR
      enterography with ultrasound for ultrasound molecular imaging (USMI) of
      inflammation in an acute small bowel inflammation of swine. METHODS: Nine swine
      with ileitis were scanned with either CT (n = 3) or MR (n = 6) enterography.
      Imaging times to load CT/MR images onto a clinical ultrasound machine, fuse them
      to ultrasound with an anatomical landmark-based approach, and identify ileitis
      were compared to the imaging times without anatomical road mapping. Inflammation
      was then assessed by USMI using dual selectin-targeted (MBSelectin) and control
      (MBControl) contrast agents in diseased and healthy control bowel segments,
      followed by ex vivo histology. RESULTS: Cross-sectional image fusion with
      ultrasound was feasible with an alignment error of 13.9 +/- 9.7 mm. Anatomical
      road mapping significantly reduced (P < 0.001) scanning times by 40%. Localising
      ileitis was achieved within 1.0 min. Subsequently performed USMI demonstrated
      significantly (P < 0.001) higher imaging signal using MBSelectin compared to
      MBControl and histology confirmed a significantly higher inflammation score (P =
      0.006) and P- and E-selectin expression (P <= 0.02) in inflamed vs. healthy
      bowel. CONCLUSIONS: Fusion of CT and MR enterography data sets with ultrasound in
      real time is feasible and allows rapid anatomical localisation of ileitis for
      subsequent quantification of inflammation using USMI. KEY POINTS: * Real-time
      fusion of CT/MRI with ultrasound to localise ileitis is feasible. * Anatomical
      road mapping using CT/MRI significantly decreases the scanning time for USMI. *
      USMI allows quantification of inflammation in swine, verified with ex vivo
      histology.

PMID- 29170799
TI  - MHC haplotype diversity in Persian Arabian horses determined using polymorphic
      microsatellites.
AB  - Previous research on the equine major histocompatibility complex (MHC)
      demonstrated strong correlations between haplotypes defined by polymorphic intra
      MHC microsatellites and haplotypes defined using classical serology. Here, we
      estimated MHC diversity in a sample of 124 Arabian horses from an endangered
      strain native to Iran (Persian Asil Arabians), using a validated 10-marker
      microsatellite panel. In a group of 66 horses related as parent-offspring pairs
      or half-sibling groups, we defined 51 MHC haplotypes, 49 of which were new. In 47
      of the remaining 58 unrelated horses, we could assign one previously identified
      MHC haplotype, and by default, we gave provisional haplotype status to the
      remaining constellation of microsatellite alleles. In these horses, we found 21
      haplotypes that we had previously defined and 31 provisional haplotypes, two of
      which had been identified in an earlier study. This gave a total of 78 new MHC
      haplotypes. The final 11 horses were MHC heterozygotes that we could not phase
      using information from any of the previously validated or provisional haplotypes.
      However, we could determine that these horses carried a total of 22 different
      undefined haplotypes. In the overall population sample, we detected three
      homozygous horses and one maternally inherited recombinant from 21 informative
      segregations. Virtually all of the horses tested were MHC heterozygotes, and most
      unrelated horses (98%) were heterozygous for rare microsatellite-defined
      haplotypes found less than three times in the sampled horses. This is evidence
      for a very high level of MHC haplotype variation in the Persian Asil Arabian
      horse.

PMID- 29170801
TI  - Immunity and immunopathology in early human life.

PMID- 29170802
TI  - Pharmacokinetics and safety of panitumumab in a patient with chronic kidney
      disease.
AB  - PURPOSE: Data on panitumumab dosing in cancer patients with renal insufficiency
      are lacking. Here, we report a 63-year-old metastatic colorectal cancer patient
      with chronic kidney injury with a glomerular filtration rate of approximately 11
      mL/min. METHODS: Pharmacokinetic parameters, including dose-normalized area under
      the curve, clearance and elimination half-life (T 1/2) after the 11th and 12th
      infusions were estimated using trapezoidal non-compartmental methods. Data were
      compared to previous reported pharmacokinetic data from studies in patients with
      normal renal function. RESULTS: The results show that the pharmacokinetic data in
      this patient with kidney failure are comparable to those in patients with
      adequate renal function. Moreover the treatment was well tolerated in this
      patient. CONCLUSION: This study suggests that panitumumab can be safely used in
      cancer patients with renal impairment without dose adjustment.

PMID- 29170803
TI  - Caenispirillum humi sp. nov., a bacterium isolated from the soil of Korean pine
      garden.
AB  - A novel bacterial strain MAH-8T was isolated from a soil sample of a Korean pine
      garden and was characterized using a polyphasic approach. Cells were Gram
      staining negative, pinkish yellow colored, motile and vibrio-shaped. The strain
      was aerobic and catalase, oxidase positive, optimum growth temperature and pH
      were 28-30  degrees C and 7.0, respectively. On the basis of 16S rRNA gene
      sequence analysis, strain MAH-8T belongs to the genus Caenispirillum and is most
      closely related to Caenispirillum bisanense KCTC 12839T (98.14%), Caenispirillum
      deserti KCTC 42064T (96.35%), and Caenispirillum salinarum JCM 17360T (95.76%).
      In DNA-DNA hybridization tests, the DNA relatedness between strain MAH-8T and its
      closest phylogenetic neighbor was below 45.0%. The DNA G + C content was 70.5
      mol% and the predominant respiratory quinone was ubiquinone-10. Flexirubin-type
      pigments were present and the major cellular fatty acids were C18:1 omega7c/C18:1
      omega6c, C16:1 omega7c/C16:1 omega6c and C16:0. The results of DNA-DNA
      hybridization and genotypic analysis in combination with chemotaxonomic and
      physiological data demonstrated that strain MAH-8T represented a novel species
      within the genus Caenispirillum, for which the name Caenispirillum humi, is
      proposed. The type strain is MAH-8T (= KACC 19294T = CGMCC 1.16224T). The NCBI
      GenBank Accession Number for the 16S rRNA gene sequence of strain MAH-8T is
      KY964275.

PMID- 29170804
TI  - First report of a symbiotic relationship between Xenorhabdus griffiniae and an
      unknown Steinernema from South Africa.
AB  - Strain WS9, a mutualistic-associated bacterium, was isolated from an unknown
      entomopathogenic Steinernema nematode, collected from a litchi orchard in
      Friedenheim, Mpumalanga, South Africa. Based on phenotypic and phylogenetic data
      of the 16S rRNA, gltX, recA, dnaN, gyrB and infB gene sequences, strain WS9 is
      identified as X. griffiniae. Strain WS9 has antibacterial activity against Gram
      positive and Gram-negative bacteria. This is the first report of an association
      between X. griffiniae and an unknown Steinernema species from South Africa.

PMID- 29170800
TI  - Early life origin of type 1 diabetes.
AB  - Type 1 diabetes (T1D) is perceived as a chronic immune-mediated disease with a
      subclinical prodromal period characterized by selective loss of insulin-producing
      beta cells in the pancreatic islets in genetically susceptible subjects. The
      incidence of T1D has increased manifold in most developed countries after World
      War II in parallel with a series of other immune-mediated diseases. T1D results
      from gene-environmental interactions. The appearance of disease-associated
      autoantibodies into the peripheral circulation is the first detectable sign of
      the initiation of the disease process leading to clinical T1D. The first
      autoantibodies may appear already before the age of 6 months and the
      seroconversion rate peaks during the second year of life. This implies that
      exogenous factors involved in the pathogenesis of T1D must be operative in early
      life, some of them most likely already during pregnancy. Here, we discuss
      putative endogenous factors that may contribute to the development of T1D during
      fetal and early postnatal life. Many environmental factors operative in early
      life have been implicated in the pathogenesis of T1D, but relatively few have
      been firmly confirmed.

PMID- 29170807
TI  - Intracellular lysophosphatidic acid influences cell migration.

PMID- 29170805
TI  - Role of actin depolymerizing factor cofilin in Aspergillus fumigatus oxidative
      stress response and pathogenesis.
AB  - Aspergillus fumigatus is a major fungal pathogen that is responsible for
      approximately 90% of human aspergillosis. Cofilin is an actin depolymerizing
      factor that plays crucial roles in multiple cellular functions in many organisms.
      However, the functions of cofilin in A. fumigatus are still unknown. In this
      study, we constructed an A. fumigatus strain overexpressing cofilin (cofilin OE).
      The cofilin OE strain displayed a slightly different growth phenotype,
      significantly increased resistance against H2O2 and diamide, and increased
      activation of the high osmolarity glycerol pathway compared to the wild-type
      strain (WT). The cofilin OE strain internalized more efficiently into lung
      epithelial A549 cells, and induced increased transcription of inflammatory
      factors (MCP-1, TNF-alpha and IL-8) compared to WT. Cofilin overexpression also
      resulted in increased polysaccharides including beta-1, 3-glucan and chitin, and
      increased transcription of genes related to oxidative stress responses and
      polysaccharide synthesis in A. fumigatus. However, the cofilin OE strain
      exhibited similar virulence to the wild-type strain in murine and Galleria
      mellonella infection models. These results demonstrated for the first time that
      cofilin, a regulator of actin cytoskeleton dynamics, might play a critical role
      in the regulation of oxidative stress responses and cell wall polysaccharide
      synthesis in A. fumigatus.

PMID- 29170806
TI  - Environmentally prevalent polycyclic aromatic hydrocarbons can elicit co
      carcinogenic properties in an in vitro murine lung epithelial cell model.
AB  - Low molecular weight (LMW) polycyclic aromatic hydrocarbons (PAH) are the most
      abundant PAHs environmentally, occupationally, and are in cigarette smoke;
      however, little is known about their carcinogenic potential. We hypothesized that
      LMW PAHs act as co-carcinogens in the presence of a known carcinogen
      (benzo[a]pyrene (B[a]P)) in a mouse non-tumorigenic type II cell line (C10
      cells). Gap junctions are commonly suppressed and inflammation induced during
      tumor promotion, while DNA-adduct formation is observed during the initiation
      stage of cancer. We used these endpoints together as markers of carcinogenicity
      in these lung adenocarcinoma progenitor cells. LMW PAHs (1-methylanthracene and
      fluoranthene, 1-10 uM total in a 1:1 ratio) were used based on previous studies
      as well as B[a]P (0-3 uM) as the classic carcinogen; non-cytotoxic doses were
      used. B[a]P-induced inhibition of gap junctional intercellular communication
      (GJIC) was observed at low doses and further reduced in the presence of the LMW
      PAH mixture (P < 0.05), supporting a role for GJIC suppression in cancer
      development. Benzo[a]pyrene diol-epoxide (BPDE)-DNA adduct levels were
      significantly induced in B[a]P-treated C10 cells and additionally increased with
      the LMW PAH mixture (P < 0.05). Significant increases in cyclooxygenase (Cox-2)
      were observed in response to the B[a]P/LMW PAH mixture combinations. DNA adduct
      formation coincided with the inhibition of GJIC and increase in Cox-2 mRNA
      expression. Significant cytochrome p4501b1 increases and connexin 43 decreases in
      gene expression were also observed. These studies suggest that LMW PAHs in
      combination with B[a]P can elicit increased carcinogenic potential. Future
      studies will further address the mechanisms of co-carcinogenesis driving these
      responses.

PMID- 29170808
TI  - Encapsulation of E. coli in biomimetic and Fe3O4-doped hydrogel: structural and
      viability analyses.
AB  - The current study reports the modification of prokaryotic microorganism through a
      single-layer technique by using different polyanions/cations and doping with
      magnetic (Fe3O4) nanoparticles. Briefly, individual Escherichia coli cells were
      encapsulated through deposition of 1% sodium alginate as first layer followed by
      depositing precipitate layers of calcium chloride, disodium hydrogen phosphate,
      and Fe3O4 nanoparticles. Surface and cross sectional analysis of modified E. coli
      cells by field emission scanning electron microscope (FE-SEM) confirmed the
      synthesis of varying sizes of artificial shells around the microbial cells while
      the deposition of Fe3O4 nanoparticles was confirmed by transmission electron
      microscope (TEM). Thermogravimetric analysis (TGA) showed the deposition of 58
      wt% of Fe3O4 nanoparticles on E. coli cell surface. Chemical structure analysis
      by Fourier transform infrared (FTIR) spectroscopy confirmed the presence of
      characteristic functional groups of deposited reagents in the hydrogel capsule.
      Zeta potential analysis of hydrogel capsule showed moderate stability with a
      surface charge of - 21 mV. Growth and viability analysis by Alamar Blue assay
      indicated marked increase in the reduction of resazurin blue (> 100%) by the
      modified E. coli indicating their viability. The movement and control of
      magnetized E. coli cells were manipulated using external permanent magnetic field
      as observed with optical microscope images. The surface-modified cells can find
      potential applications in bioremediation, biodegradation, and catalysis and can
      be used as biosorbents.

PMID- 29170809
TI  - Favorable evolution of lung interstitial disease in a patient with chronic
      myelomonocytic leukemia treated with azacitidine.

PMID- 29170811
TI  - Triple elastofibromas located in the supra- and infrascapular regions-a case
      report.
AB  - We report a case of triple elastofibromas located in the supra- and infrascapular
      regions. A 61-year-old female with a history of bilateral elastofibroma in the
      typical subscapular region (6 years before) was admitted for the evaluation of a
      left-sided suprascapular mass that she had first noted 3 months before. On
      physical examination, a firm, painless, mobile mass was palpated in the
      subcutaneous tissue. The patient had not observed any changes of the two known
      lesions over the past 6 years. The patient denied a family history of
      elastofibroma. The signal characteristic on T1- and T2-weighted images as well as
      contrast enhancement curves on dynamic study was identical in all three masses.
      Ultrasound-guided biopsy performed before surgical intervention confirmed the
      diagnosis of elastofibroma. This case report has a teaching value as, to our
      knowledge, it is the only one in the literature with images of synchronous
      elastofibromas documented by dynamic contrast-enhanced MRI. In cases of
      elastofibroma with diagnostic difficulties, particularly in uncommon sites, a
      dynamic contrast-enhanced MRI may help to establish the proper diagnosis. This
      case report gives an example of rare multiple elastofibromas, presents current
      diagnostic imaging methods, and reminds us that elastofibroma is not exclusive to
      the posterior thoracic region.

PMID- 29170810
TI  - Correlation study between osteoporosis and hematopoiesis in the context of
      adjuvant chemotherapy for breast cancer.
AB  - This retrospective study attempts to establish if a correlation exists between
      osteoporosis and hematopoiesis before and after adjuvant chemotherapy in the
      context of non-metastatic breast cancer. Osteoporosis is interpreted both as a
      direct marker of osteoblastic decline and as an indirect marker of increased bone
      marrow adiposity within the hematopoietic microenvironment. Patients from the
      "Centre du Sein" at CHUV (Centre Hospitalier Universitaire Vaudois) undergoing
      adjuvant chemotherapy were included in this study. Evolution of blood counts was
      studied in correlation with the osteoporosis status. Toxicity of chemotherapy was
      coded according to published probability of febrile neutropenia. One hundred
      forty-three women were included: mean age 52.1 +/- 12.5 years, mean BMI (body
      mass index) 24.4 +/- 4.1. BMD (bone mineral density) scored osteoporotic in 32%
      and osteopenic in 45%. Prior to chemotherapy, BMD was positively correlated with
      neutrophil (p < 0.001) and thrombocyte (p = 0.01) count; TBS (trabecular bone
      score) was not correlated with blood count. After the first cycle of
      chemotherapy, an increase of one point in TBS correlated with a decrease of 57%
      on the time to reach leucocyte nadir (p = 0.004). There was a positive
      correlation between BMD and risk of infection (p < 0.001). Our data demonstrates
      an association between osteoporosis and lower blood counts in a younger cohort
      than previously published, extending it for the first time to neutrophil counts
      in females. Our results suggest that the healthier the bone, the earlier the
      lowest leucocyte count value, prompting further research on this area.

PMID- 29170812
TI  - Avulsion fracture of an ossified pes anserinus tendon post-lateral patellar
      dislocation.
AB  - The pes anserinus is a common tendon comprising the tendinous insertions of the
      sartorius, gracilis, and semitendinosus muscles. It inserts at the anteromedial
      aspect of the tibia and plays a significant role in stabilization of the medial
      side of the knee joint. The current article presents a case with recurrent
      lateral patellar dislocations causing chronic stress along the medial knee
      stabilizers and consecutive enthesophyte formation at the insertion of the pes
      anserinus tendon that showed a transverse fracture upon a subsequent incident of
      traumatic lateral patellar dislocation. Avulsion injuries of the pes anserinus
      tendon are rarely encountered, and to our knowledge, association with recurrent
      lateral patellar dislocations has not been described before.

PMID- 29170813
TI  - MRI in chronic groin pain: sequence diagnostic reliability compared to systematic
      surgical assessment.
AB  - OBJECTIVE: To determine the diagnostic reliability of magnetic resonance imaging
      (MRI) sequences in chronic groin pain (CGP) compared to surgery and try to
      propose a suitable MRI protocol. MATERIALS AND METHODS: Forty-three consecutive
      patients with resistant clinical CGP underwent a pre-surgical pelvis MRI. Eight
      MRI sequences were acquired: axial fast spin-echo T1-weighted (FSE T1), coronal
      FSE T1, axial-oblique (in symphysis plane) proton density weighted with fat
      saturation (PDFS), coronal PDFS, sagittal PDFS, axial FSE T1 with fat saturation
      and gadolinium enhancement (FSGE), coronal FSE T1 FSGE and axial FSE T1 with
      Valsalva maneuver (VM). These sequences were reviewed for pubic symphysis
      assessment, adductor longus (AL) tendon and abdominal wall (AW) injuries. The
      same surgeon operated on all of these patients (26 AL and 49 AW). Sensitivity
      (Se), specificity (Sp), positive predictive value (PPV), negative prospective
      value (NPV) and accuracy of each sequence and combinations for AL or AW injuries
      were calculated in comparison to surgical findings. RESULTS: One hundred ninety
      two sequences were obtained. Coronal T1 FSGE and axial T1 VM proved to be the
      most reliable sequences (accuracy: 91.67% in AL and 83.33% in AW). The best
      sequence combination was coronal T1, axial PDFS, sagittal PDFS and axial T1 VM
      (accuracy: 77.78%; Se: 100.00%, Sp: 69.23%, PPV: 55.56%, NPV: 100.00%).
      CONCLUSION: MRI has 77.78% accuracy, 100.00% sensitivity, 69.23% specificity,
      55.56% PPV and 100.00% NPV in evaluating CGP, with coronal T1-axial PDFS-sagittal
      PDFS-axial T1 VM as the optimal protocol in terms of diagnostic performance
      within a reasonable scan time. Diagnostic performance of MRI was examined in the
      evaluation of CGP using surgery as reference standard.

PMID- 29170815
TI  - Management of post-midurethral sling voiding dysfunction. International
      Urogynecological Association research and development committee opinion.
AB  - Voiding dysfunction following midurethral sling procedures is not a rare event.
      There is no current consensus regarding management of this complication. Although
      it is often transient and self-limiting, chronic post-midurethral sling voiding
      dysfunction may lead to irreversible changes affecting detrusor function. Initial
      management includes intermittent catheterization, and addressing circumstantial
      factors interfering with normal voiding, such as pain. Early sling mobilization
      often resolves the dysfunction, and is associated with minimal morbidity. Sling
      incision or excision at a later stage, although fairly effective, could be
      associated with recurrence of stress urinary incontinence. There is insufficient
      evidence to justify urethral dilatation in this context.

PMID- 29170816
TI  - Umbilical cord entanglement's frequency and its impact on the newborn.
AB  - Neonaticide is a serious allegation that needs a complete chain of criminal
      investigations. In this context, a nuchal cord is considered to be responsible
      for an infant's death, but there is a clear lack of evidence. The purpose of our
      study is to reveal if a nuchal cord can be responsible for stillbirth, poor
      perinatal outcome, or neonatal death in the forensic aspect. We conducted a
      prospective study in collaboration with the Augustinian Sisters' Hospital in
      Cologne, Germany in the period from February 2014 to May 2016. Four-hundred
      eighty-six children were enrolled. All births were assessed regarding the
      occurrence of an umbilical cord entanglement, and perinatal outcome was measured
      by arterial blood gas analysis, Apgar after 1, 5, and 10 min after birth as well
      as the general vitality. The prevalence of a nuchal cord was 16.87%. Apgar
      decrease and acidosis were significantly associated with a nuchal cord. No
      adverse perinatal outcome was recorded in this constellation. There was no child
      death regarding the first 24 h, and no mother experienced a syncope while giving
      birth. We can conclude that a nuchal cord is not associated with adverse
      perinatal outcome.

PMID- 29170818
TI  - Reviewer's comment concerning "Lumbar total disc replacement: predictors for 8
      year outcome" (by H. Furunes et al. [2017] Eur Spine J).

PMID- 29170817
TI  - Postmortem 1H-MRS-Detection of Ketone Bodies and Glucose in Diabetic
      Ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is a metabolic complication of diabetes mellitus that
      takes a lethal course if untreated. In this way relevant to forensic medicine,
      secure diagnosis of DKA usually involves the evidence of elevated levels of
      glucose and the ketone bodies acetone, acetoacetate, and beta-hydroxybutyrate in
      corpse fluids. We conducted a postmortem hydrogen proton magnetic resonance
      spectroscopy (1H-MRS) in a case of lethal DKA. Distinctive resonances of all
      three ketone bodies as well as glucose were visible in spectra of cerebrospinal
      fluid, vitreous humor, and white matter. Estimated concentrations of ketone
      bodies and glucose supported the findings both of autopsy and biochemical
      analysis. Advantages of human postmortem 1H-MRS are the lack of movement and flow
      artifacts as well as lesser limitations of scan duration. Postmortem 1H-MRS is
      able to non-invasively measure concentrations of glucose and ketone bodies in
      small volumes of various regions of the brain. It may thus become a diagnostic
      tool for forensic investigations by quick determination of pathological
      metabolite concentrations in addition to conventional autopsy.

PMID- 29170819
TI  - Tongue Pressure Production and Submental Surface Electromyogram Activities During
      Tongue-Hold Swallow with Different Holding Positions and Tongue Length.
AB  - Our previous study regarding the tongue-hold swallow (THS) demonstrated that the
      tongue-to-palate contact during THS could be influenced by the maximum tongue
      protrusion length (MTPL) of individual subjects, resulting in two different
      patterns of pressure generation. The present study further analyzed the influence
      of MTPL on the tongue pressure production along with submental surface
      electromyography (sEMG) during THS, in order to establish an index to better
      control THS effects. Tongue pressure using a sensor sheet system and concurrent
      submental sEMG activities were measured during swallowing tasks in 18 healthy
      young adults. Task conditions comprised THS at two different degrees of tongue
      protrusion and dry swallow. Tongue pressures and sEMG activities were compared
      among three task conditions, and correlations of MTPL with tongue pressure were
      also investigated. Additionally, a ROC curve was used to find a cut-off value for
      MTPL to predict changes (increases and decreases) in tongue pressure during THS.
      The duration and the amount of submental muscle activity increased concurrently
      during THS. Two trends were shown on the change in tongue pressure at the
      posterior-circumferential part of the hard palate during THS compared to dry
      swallow; the maximal magnitude and the integrated value of tongue pressure
      increased in some subjects, while these values decreased in others. Thirty-two
      millimeters was found to be the cut-off value of MTPL, which distinguishes
      increase/decrease pattern of tongue pressure with sensitivities of 60.0-85.7%.
      The present finding suggests that more reliable THS effects should be attainable
      using MTPL to set the tongue-hold position.

PMID- 29170820
TI  - Decoupling habitat fragmentation from habitat loss: butterfly species mobility
      obscures fragmentation effects in a naturally fragmented landscape of lake
      islands.
AB  - Since the publication of the theory of island biogeography, ecologists have
      postulated that fragmentation of continuous habitat presents a prominent threat
      to species diversity. However, negative fragmentation effects may be artifacts;
      the result of species diversity declining with habitat loss, and habitat loss
      correlating positively with degree of fragmentation. In this study, we used
      butterfly assemblages on islands of Lake of the Woods, Ontario, Canada to
      decouple habitat fragmentation from habitat loss and test two competing
      hypotheses: (1) the island effect hypothesis, which predicts that decreasing
      fragment size and increasing fragment isolation reduces species diversity beyond
      the effects of habitat loss, and (2) the habitat amount hypothesis, which negates
      fragmentation effects and predicts that only total habitat area determines the
      diversity of species persisting on fragmented landscapes. Using eight independent
      size classes of islands (ranging from 0.1 to 8.0 ha) that varied in number of
      islands while holding total area constant, species diversity comparisons, species
      accumulation curves, and species-area relationship extrapolations demonstrated
      that smaller insular habitats contained at least as many butterfly species as
      continuous habitat. However, when highly mobile species occurring on islands
      without their larval food plants were excluded from analyses, island effects on
      potentially reproducing species became apparent. Similarily, generalized linear
      models suggested that effects of island isolation and vascular plant richness on
      insular butterfly richness were confounded by species of high mobility. We
      conclude that inter-fragment movements of highly mobile species may obscure
      important fragmentation effects on potentially reproducing populations,
      questioning support for the habitat amount hypothesis.

PMID- 29170821
TI  - Weather-driven change in primary productivity explains variation in the amplitude
      of two herbivore population cycles in a boreal system.
AB  - Vertebrate populations throughout the circumpolar north often exhibit cyclic
      dynamics, and predation is generally considered to be a primary driver of these
      cycles in a variety of herbivore species. However, weather and climate play a
      role in entraining cycles over broad landscapes and may alter cyclic dynamics,
      although the mechanism by which these processes operate is uncertain.
      Experimental and observational work has suggested that weather influences primary
      productivity over multi-year time periods, suggesting a pathway through which
      weather and climate may influence cyclic herbivore dynamics. Using long-term
      monitoring data, we investigated the relationships among multi-year weather
      conditions, measures of primary productivity, and the abundance of two cyclic
      herbivore species: snowshoe hare and northern red-backed vole. We found that
      precipitation (rain and snow) and growing season temperatures were strongly
      associated with variation in primary productivity over multi-year time horizons.
      In turn, fourfold variation in the amplitude of both the hare and vole cycles
      observed in our study area corresponded to long-term changes in primary
      productivity. The congruence of our results for these two species suggests a
      general mechanism by which weather and climate might influence cyclic herbivore
      population dynamics. Our findings also suggested that the association between
      climate warming and the disappearance of cycles might be initiated by changes in
      primary productivity. This work provides an explanation for observed influences
      of weather and climate on primary productivity and population cycles and will
      help our collective understanding of how future climate warming may influence
      these ecological phenomena in the future.

PMID- 29170822
TI  - Correction to: The antidepressant effect of musk in an animal model of
      depression: a histopathological study.
AB  - The original publication of this paper contains mistake. Below you will find the
      needed corrections.

PMID- 29170824
TI  - An analysis of the risk factors of anastomotic stricture after esophagectomy.
AB  - PURPOSE: Anastomotic stricture after esophagectomy is a major cause of long-term
      morbidity and a poor quality of life. The aim of this study was to identify the
      risk factors for the development of anastomotic stricture after esophagectomy.
      METHODS: The study subjects were 213 patients who underwent esophagectomy for
      squamous cell carcinoma of the esophagus between 2012 and 2014. Anastomotic
      stricture was defined as stenosis at the site of anastomosis that required
      endoscopic dilation. Refractory stricture was defined as that requiring more than
      four sessions of dilations. Univariate and multivariate logistic regression
      analyses were used to identify the potential risk factors for the development of
      anastomotic stricture. RESULTS: In this retrospective study, 29 patients (13.6%)
      developed anastomotic stricture within a median period of 108 postoperative days
      and required a median of 2 dilations. Tumors located in the upper part of the
      esophagus (p = 0.004), the presence of cardiovascular disease (p = 0.024) and
      anastomotic leakage (p = 0.002) were identified as independent risk factors for
      the development of anastomotic stricture. The time to the diagnosis of refractory
      stricture (85 +/- 33 days) was significantly shorter than that of non-refractory
      stricture (171 +/- 22 days, p = 0.038). CONCLUSIONS: Patients with squamous cell
      carcinoma in the upper esophagus with cardiovascular disease who develop
      postoperative anastomotic leakage should be carefully monitored to prevent the
      development of benign anastomotic stricture.

PMID- 29170825
TI  - [Psychosomatic medicine in old age].
AB  - Approximately 25% of people over 65 years old suffer from psychiatric disorders
      but in cases of simultaneously occurring somatic diseases the prevalence is
      increased. Sickness, loss of important reference persons and life crises in older
      age often reactivate traumatic experiences from earlier life stages. It can be
      difficult to differentiate between psychological disorders and the psychological
      symptoms accompanying somatic illness. The biographic medical history and
      estimation of cognitive skills within a geriatric basis assessment should be
      standard in geriatric diagnostics. Psychological disorders are often overlooked
      or inadequately treated in older people. In the case of psychopharmacological
      treatment, effects on somatic sickness as well as drug-drug interactions have to
      be kept in mind. Psychotherapeutic approaches focusing on resources and social
      support particularly in group therapy seem to be very helpful.

PMID- 29170823
TI  - Engineering new neurons: in vivo reprogramming in mammalian brain and spinal
      cord.
AB  - Neurons are postmitotic. Once lost because of injury or degeneration, they do not
      regenerate in most regions of the mammalian central nervous system. Recent
      advancements nevertheless clearly reveal that new neurons can be reprogrammed
      from non-neuronal cells, especially glial cells, in the adult mammalian brain and
      spinal cord. Here, we give a brief overview concerning cell fate reprogramming in
      vivo and then focus on the underlying molecular and cellular mechanisms.
      Specifically, we critically review the cellular sources and the reprogramming
      factors for in vivo neuronal conversion. Influences of environmental cues and the
      challenges ahead are also discussed. The ability of inducing new neurons from an
      abundant and broadly distributed non-neuronal cell source brings new perspectives
      regarding regeneration-based therapies for traumatic brain and spinal cord
      injuries and degenerative diseases.

PMID- 29170826
TI  - Increased pericardial adipose tissue and cardiometabolic risk in patients with
      schizophrenia versus healthy controls.
AB  - Patients with schizophrenia are at increased risk of diabetes, cardiovascular
      disease (CVD) and associated mortality versus the general population. Increased
      intra-abdominal and pericardial adipose tissue are associated with elevated CVD
      and mortality in the general population, but little is known about these in
      patients with schizophrenia. This study examined pericardial and intra-abdominal
      adipose tissue in schizophrenia and compared this to healthy controls. Thirty-one
      patients with schizophrenia (mean age 41.2 years, 76% males) and 30 healthy
      volunteers (CTRL) were examined in this study. The primary outcomes were the
      volumes of pericardial adipose tissue and intra-abdominal adipose tissue,
      measured using magnetic resonance imaging. Secondary outcomes included diabetes
      and cardiac event risk assessed by established instruments. Volumes of
      pericardial adipose tissue were increased in male and female patients with
      schizophrenia compared to healthy controls after the adjustment of age, sex and
      body mass index (P < 0.005). The 10-year risk of a cardiac event was
      significantly higher in patients with schizophrenia. Furthermore, the risk for
      developing type-2 diabetes mellitus was slightly increased in schizophrenia.
      Volumes of intra-abdominal adipose tissue were slightly increased in male and
      female patients with schizophrenia, albeit not statistically significant. This
      study demonstrates that patients with schizophrenia have increased pericardial
      adipose tissue versus controls. This increased fat deposit around the heart is
      highly relevant for understanding the comorbidity between heart disease and
      schizophrenia. Interventions aiming to reduce pericardial and intra-abdominal
      adipose tissue, such as exercise, may be essential to reduce the burden of heart
      disease in schizophrenia.

PMID- 29170828
TI  - A novel trifunctional, family GH10 enzyme from Acidothermus cellulolyticus 11B,
      exhibiting endo-xylanase, arabinofuranosidase and acetyl xylan esterase
      activities.
AB  - A novel, family GH10 enzyme, Xyn10B from Acidothermus cellulolyticus 11B was
      cloned and expressed in Escherichia coli. This enzyme was purified to homogeneity
      by binding to regenerated amorphous cellulose. It had higher binding on Avicel as
      compared to insoluble xylan due to the presence of cellulose-binding domains,
      CBM3 and CBM2. This enzyme was optimally active at 70  degrees C and pH 6.0. It
      was stable up to 70  degrees C while the CD spectroscopy analysis showed thermal
      unfolding at 80  degrees C. Xyn10B was found to be a trifunctional enzyme having
      endo-xylanase, arabinofuranosidase and acetyl xylan esterase activities. Its
      activities against beechwood xylan, p-Nitrophenyl arabinofuranoside and p
      Nitrophenyl acetate were found to be 126,480, 10,350 and 17,250 U MUmol-1,
      respectively. Xyn10B was highly active producing xylobiose and xylose as the
      major end products, as well as debranching the substrates by removing arabinose
      and acetyl side chains. Due to its specific characteristics, this enzyme seems to
      be of importance for industrial applications such as pretreatment of poultry
      cereals, bio-bleaching of wood pulp and degradation of plant biomass.

PMID- 29170827
TI  - The role of nanomaterials in cell delivery systems.
AB  - In more than one decade, cell transplantation has created an important strategy
      to treat a wide variety of diseases characterized by tissue and cell
      dysfunctions. In this course of action, cell delivery to target site has been
      always one of the most important constraints and complications, as only a small
      proportion of the cells are housed in the target sites. Nanotechnology and
      nanoscale biomaterials have been helpful for cell transplantation in various
      fields of regenerative medicine including diagnosis, delivery systems for the
      cell, drug or gene, and cells protection system. In this study, the basic
      concepts and recently studied aspects of cell delivery systems based on nanoscale
      biomaterials for transplantation and clinical applications are highlighted.
      Nanomaterials may be used in combination with cell therapy to control the release
      of drugs or special factors of engineered cells after transplantation.

PMID- 29170829
TI  - Correction to: Molecular characterization of a genetically divergent equine
      pegivirus strain identified in China.
AB  - Unfortunately, the corresponding author name was incorrectly published in the
      original article and the same is corrected here. The original article was
      corrected.

PMID- 29170830
TI  - Genetic analysis of three porcine bocaparvoviruses and identification of a
      natural recombinant breakpoint in NS1.
AB  - In this study, we obtained the whole genomes of three porcine bocaparvovirus
      (PBoV) strains (GD6, GD10, and GD23) by polymerase chain reaction. Sequence
      analysis showed that all three field strains belonged to PBoV group 3 (G3). The
      phylogenetic trees based on NS1, NP1, and VP1 differed to the extent that these
      PBoVs were potentially more closely related to bocaparvoviruses known to infect
      other animals than to other PBoVs. GD6, GD10, and GD23 all included the conserved
      sequences YLGPF and HDXXY, with known phospholipase A2 activity. Using
      recombination-detection software we identified a natural recombinant breakpoint
      in the NS1 region of PBoV G3. The results of this study will further the
      epidemiological characterization of PBoVs.

PMID- 29170831
TI  - Mutation independently affects reproductive traits and dauer larvae development
      in mutation accumulation lines of Caenorhabditis elegans.
AB  - Developmental decisions are important in organismal fitness. For the nematode
      Caenorhabditis elegans, which is naturally found in the ephemeral food patches
      formed by rotting plant material, correctly committing to dauer or non-dauer
      larval development is key to genotype survival. To investigate the link between
      reproductive traits, which will determine how populations grow, and dauer larvae
      formation, we have analysed these traits in mutation accumulation lines of C.
      elegans. We find that reproductive traits of individual worms-the total number of
      progeny and the timing of progeny production-are highly correlated with the
      population size observed in growing populations. In contrast, we find no
      relationship between reproduction traits and the number of dauer larvae observed
      in growing populations. We also do not observe a mutational bias in dauer larvae
      formation. These results indicate that the control of dauer larvae formation is
      distinct from the control of reproduction and that differences in dauer larvae
      formation can evolve rapidly.

PMID- 29170832
TI  - Spectrophotometric determination of anionic surfactants: optimization by response
      surface methodology and application to Algiers bay wastewater.
AB  - A simple analytical method for quantitative determination of an anionic
      surfactant in aqueous solutions without liquid-liquid extraction is described.
      The method is based on the formation of a green-colored ion associate between
      sodium dodecylbenzenesulfonate (SDBS) and cationic dye, Brilliant Green (BG) in
      acidic medium. Spectral changes of the dye by addition of SDBS are studied by
      visible spectrophotometry at maximum wave length of 627 nm. The interactions and
      micellar properties of SDBS and cationic dye are also investigated using surface
      tension method. The pH, the molar ratio ([BG]/[SDBS]), and the shaking time of
      the solutions are considered as the main parameters which affect the formation of
      the ion pair. Determination of AS in distilled water gives a significant
      detection limit up to 3 * 10-6 M. The response surface methodology (RSM) is
      applied to study the absorbance. A Box-Behnken is a model designed to the
      establishment of responses given by parameters with great probability. This model
      is set up by using the three main parameters at three levels. Analysis of
      variance shows that only two parameters affect the absorbance of the ion pair.
      The statistical results obtained are interesting and give us real possibility to
      reach optimum conditions for the formation of the ion pair. As the proposed
      method is free from interferences from major constituents of water, it has been
      successfully applied to the determination of anionic surfactant contents in
      wastewaters samples collected from Algiers bay.

PMID- 29170833
TI  - Inclusion of Assistive Technologies in a Basic Package of Essential Healthcare
      Service.
AB  - This paper outlines the potential and necessity of the development of assistive
      technologies (AT) for people with intellectual disabilities (IDs). We analyse a
      policy recommendation designed to determine the contents of a basic health
      package supplied by the state, known as the Dunning Funnel. We contend that the
      Dunning Funnel is a useful methodology, but is weakened by a potentially
      relativistic understanding of "necessity" in relation to the requirements of
      people with IDs (i.e., community standards will determine whether AT are
      necessary). We remedy this defect by using the capabilities approach as outlined
      by Martha Nussbaum. We argue that this approach provides a strong normative case
      for ensuring that communities provide help to people with IDs, if those
      communities are to achieve a minimal standard of justice. However, the
      capabilities approach does not offer much specific guidance on how AT ought to be
      distributed, nor does it offer guidance on risks, like the bottomless pit
      problem. We propose that the Dunning Funnel used in combination with the
      capabilities approach will provide a suitable heuristic for determining the
      distribution of AT in a basic health package.

PMID- 29170835
TI  - Entomopathogen ID: a curated sequence resource for entomopathogenic fungi.
AB  - We report the development of a publicly accessible, curated nucleotide sequence
      database of hypocrealean entomopathogenic fungi. The goal is to provide a
      platform for users to easily access sequence data from taxonomic reference
      strains. The database can be used to accurately identify unknown entomopathogenic
      fungi based on sequence data for a variety of phylogenetically informative loci.
      The database provides full multi-locus sequence alignment capabilities. The
      initial release contains data compiled for 525 strains covering the phylogenetic
      diversity of three important entomopathogenic families: Clavicipitaceae,
      Cordycipitaceae, and Ophiocordycipitaceae. Furthermore, Entomopathogen ID can be
      expanded to other fungal clades of insect pathogens, as sequence data becomes
      available. The database will allow isolate characterisation and evolutionary
      analyses. We contend that this freely available, web-accessible database will
      facilitate the broader community to accurately identify fungal entomopathogens,
      which will allow users to communicate research results more effectively.

PMID- 29170834
TI  - Emerging roles of cortical microtubule-membrane interactions.
AB  - Plant cortical microtubules have crucial roles in cell wall development. Cortical
      microtubules are tightly anchored to the plasma membrane in a highly ordered
      array, which directs the deposition of cellulose microfibrils by guiding the
      movement of the cellulose synthase complex. Cortical microtubules also interact
      with several endomembrane systems to regulate cell wall development and other
      cellular events. Recent studies have identified new factors that mediate
      interactions between cortical microtubules and endomembrane systems including the
      plasma membrane, endosome, exocytic vesicles, and endoplasmic reticulum. These
      studies revealed that cortical microtubule-membrane interactions are highly
      dynamic, with specialized roles in developmental and environmental signaling
      pathways. A recent reconstructive study identified a novel function of the
      cortical microtubule-plasma membrane interaction, which acts as a lateral fence
      that defines plasma membrane domains. This review summarizes recent advances in
      our understanding of the mechanisms and functions of cortical microtubule
      membrane interactions.

PMID- 29170836
TI  - Phase-contrast cerebrospinal fluid flow magnetic resonance imaging in qualitative
      evaluation of patency of CSF flow pathways prior to infusion of chemotherapeutic
      and other agents into the fourth ventricle.
AB  - PURPOSE: Nuclear medicine studies have previously been utilized to assess for
      blockage of cerebrospinal fluid (CSF) flow prior to intraventricular chemotherapy
      infusions. To assess CSF flow without nuclear medicine studies, we obtained cine
      phase-contrast MRI sequences that assess CSF flow from the fourth ventricle down
      to the sacrum. METHODS: In three clinical trials, 18 patients with recurrent
      malignant posterior fossa tumors underwent implantation of a ventricular access
      device (VAD) into the fourth ventricle, either with or without simultaneous tumor
      resection. Prior to infusing therapeutic agents into the VAD, cine MRI phase
      contrast CSF flow sequences of the brain and total spine were performed. Velocity
      encoding (VENC) of 5 and 10 cm/s was used to confirm CSF flow from the fourth
      ventricular outlets to the cervical, thoracic, and lumbar spine. Qualitative CSF
      flow was characterized by neuroradiologists as present or absent. RESULTS: All 18
      patients demonstrated CSF flow from the outlets of the fourth ventricle down to
      the sacrum with no evidence of obstruction. One of these patients, after disease
      progression, subsequently showed obstruction of CSF flow. No patient required a
      nuclear medicine study to assess CSF flow prior to initiation of infusions.
      Fourteen patients have received infusions to date, and none has had neurological
      toxicity. CONCLUSIONS: CSF flow including the fourth ventricle and the total
      spine can be assessed noninvasively with phase-contrast MRI sequences. Advantages
      over nuclear medicine studies include avoiding both an invasive procedure and
      radiation exposure.

PMID- 29170837
TI  - Post-traumatic carotid-cavernous fistula in a pediatric patient: a case-based
      literature review.
AB  - BACKGROUND: Carotid-cavernous fistula (CCF) is a shunt between the carotid artery
      and the cavernous sinus. Traumatic CCFs are diagnosed in 0.2% of head traumas
      being only 4.6% of the pediatric population. Classified by Barrow in 1985, type A
      CCF is the most frequent, occurring in 75% of cases. Type A is characterized by
      direct and high-flow CCF that generally can occur as a result of traumatic injury
      or rupture of an intracavernous aneurysm. CASE PRESENTATION: The subject was an 8
      year-old boy with penetrating trauma to his left eye. During the initial
      evaluation, a computed tomography (CT) scan was unremarkable, and after relief of
      symptoms, the patient was discharged. Seven days later, he developed grade I
      proptosis, conjunctival chemosis, ophthalmoplegia (III, IV, and VI cranial nerve
      palsies), and left-sided ptosis and mydriasis. Arteriography confirmed a post
      traumatic CCF, and the patient was treated with an endovascular detachable
      balloon. CONCLUSION: CCF should be suspected in craniofacial traumas with ocular
      symptoms. The presence of a skull base fracture on CT is a poor predictor of CCF
      associated with head trauma. Early diagnosis and treatment can prevent permanent
      neurological deficits and unfavorable outcomes.

PMID- 29170838
TI  - Embolization of a traumatic arteriovenous fistula between the middle meningeal
      artery and middle meningeal vein in a child with pulsatile tinnitus.
AB  - Traumatic arteriovenous fistulas (AVFs) involving the middle meningeal artery
      (MMA) are uncommon lesions and rare in the pediatric population. An adolescent
      with headaches developed a bruit and a rhythmic "swooshing" noise in the left ear
      9 weeks after a traumatic brain injury involving a left temporal bone fracture.
      An MRA of the brain demonstrated an enlarged left MMA and arterialized flow in
      the left middle meningeal vein (MMV), suggestive of an AVF. Cerebral angiography
      confirmed and characterized the left MMA-MMV fistula, which drained into the
      pterygoid plexus. The patient underwent transarterial coil embolization, with
      successful obliteration of the fistulous connection, and her tinnitus resolved.
      This case illustrates the importance of recognizing a post-traumatic AVF in a
      pediatric patient with pulsatile tinnitus, and that endovascular treatment by
      coil embolization is a safe and effective treatment option.

PMID- 29170839
TI  - Transanal hemorrhoidal dearterialization (THD) for hemorrhoidal disease: a single
      center study on 1000 consecutive cases and a review of the literature.
AB  - BACKGROUND: The transanal hemorrhoidal dearterialization (THD) Doppler procedure
      is a minimally invasive technique to treat symptomatic hemorrhoids. The aim of
      the study was to assess the clinical efficacy and the satisfaction of patients in
      a large series treated with THD and to review the relevant literature. METHODS:
      In this retrospective, single-institution, study consecutive patients with grade
      2, 3, or 4 hemorrhoidal disease were treated with the THD Doppler procedure.
      Dearterialization was performed in all cases and mucopexy in case of prolapse.
      The dearterialization procedure evolved from "proximal artery ligation" to
      "distal Doppler-guided dearterialization." Follow-up was scheduled at 15 days, 1,
      3, 12 months, and once a year thereafter. Complications were recorded. Clinical
      efficacy was assessed comparing both frequency of symptoms and disease grading
      (Goligher's classification) at baseline versus last follow-up. Uni-/multivariate
      analysis evaluated factors affecting the outcome. RESULTS: There were 1000
      patients (619 men; mean age: 48.6 years, range 19-88 years). Acute postoperative
      bleeding was observed in 14 patients (1.4%), pain/tenesmus in 31 patients (3.1%),
      and urinary retention in 23 patients (2.3%). At mean follow-up duration of 44 +/-
      29 months, the symptomatic recurrence rate was 9.5% (95 patients; bleeding in 12
      (1.2%), prolapse in 46 (4.6%), and bleeding and prolapse in 37 (3.7%) patients).
      The recurrence rate was 8.5, 8.7, and 18.1% in patients with grade 2, 3, and 4
      hemorrhoids, respectively. Seventy out of 95 patients with recurrence needed
      surgery (reoperation rate: 7.0%). At final follow-up and taking into account the
      reoperations, 95.7% of patients had no hemorrhoidal disease on examination.
      Younger age, grade 4 disease, and high artery ligation affected the outcome
      negatively. CONCLUSIONS: Our results show that the THD Doppler procedure is safe
      and effective in patients with hemorrhoidal disease and associated with low
      morbidity and recurrence rates and a high rate percentage of treatment success.

PMID- 29170840
TI  - Early detection of cardiac alterations by left atrial strain in patients with
      risk for cardiac abnormalities with preserved left ventricular systolic and
      diastolic function.
AB  - This study sought to examine whether early cardiac alterations could be detected
      by left atrial (LA) strain in patients with risk for cardiac abnormalities. In
      this cross-sectional and retrospective study, we included patients with (n = 234)
      and without (n = 48) risk for cardiac abnormalities (i.e. those with arterial
      hypertension, diabetes mellitus and/or a history of coronary artery disease) of
      similar age and with preserved left ventricular (LV) systolic and diastolic
      function according to standard criteria. LA strain was significantly altered in
      patients with risk for cardiac abnormalities in comparison to those without risk
      (29.2 +/- 8.6 vs. 38.5 +/- 12.6%; rate of impaired LA strain: 18.8% vs. 0%; all p
      < 0.01) and was the most sensitive parameter to detect early LA alterations in
      comparison with other LA functional parameters (rate of impaired LA strain rate,
      LA total emptying fraction, and LA expansion index 3.8%, 7.3%, and 3.8%,
      respectively). Moreover, in patients with risk for cardiac abnormalities LA
      strain was altered even in the absence of subtle LV systolic and diastolic
      alterations (rates 13.9% and 6.8%), albeit to a lesser extent than in patients
      with an abnormal LV longitudinal systolic strain or abnormal mitral annular e'
      velocities (rates 48.5% and 24.4%). Regarding the clinical relevance of these
      findings, an impaired LA strain (i.e. < 23%) was significantly linked to
      exertional dyspnea (OR 3.5 [1.7-7.0]) even adjusting the analyses by age, gender
      and subtle LV abnormalities. In conclusion, the findings from this study suggest
      that LA strain measurements could be useful to detect early cardiac alterations
      in patients with risk for cardiac abnormalities with preserved LV systolic and
      diastolic function and that these early LA strain alterations could be linked to
      exertional dyspnea.

PMID- 29170841
TI  - Oxymatrine induces apoptosis and inhibits invasion in Gallbladder carcinoma via
      PTEN/PI3K/AKT pathway.
AB  - Oxymatrine extracted from Sophora flavescens Ait as a natural polyphenolic
      phytochemical has been demonstrated to exhibit anti-tumor effects on various
      cancers, including Gallbladder carcinoma (GBC). However, its underlying
      mechanisms of function are largely unknown in GBC cells. The present study is
      conducted to investigate the anti-tumor effects and the underlying mechanisms of
      oxymatrine on GBC cells in vitro and in vivo. The results showed that oxymatrine
      inhibited cell viability, metastatic ability and induced cell apoptosis in dose
      dependent manners. Furthermore, we found that the expression of p-AKT, MMP-2, MMP
      9 and the ratio of Bcl-2/Bax were significantly down-regulated, while the
      expression of PTEN was up-regulated in GBC cells. In addition, pretreatment with
      a specific PI3K/AKT activator (IGF-1) significantly antagonized the oxymatrine
      mediated inhibition of GBC-SD cells. Subsequently, our in vivo studies showed
      that administration of oxymatrine induced a significant dose-dependent decrease
      in tumor growth. In conclusion, these findings indicated that the inhibition of
      cells proliferation, migration, invasion and the induction of apoptosis in
      response to oxymatrine in GBC cells, may function through the suppression of
      PTEN/PI3K/AKT pathway, which was considered as the vital signaling pathway in
      regulating tumorigenesis. These results suggested that oxymatrine might be a
      novel effective candidate as chemotherapeutic agent against GBC.

PMID- 29170842
TI  - Electropore Formation in Mechanically Constrained Phospholipid Bilayers.
AB  - Molecular dynamics simulations of lipid bilayers in aqueous systems reveal how an
      applied electric field stabilizes the reorganization of the water-membrane
      interface into water-filled, membrane-spanning, conductive pores with a
      symmetric, toroidal geometry. The pore formation process and the resulting
      symmetric structures are consistent with other mathematical approaches such as
      continuum models formulated to describe the electroporation process. Some
      experimental data suggest, however, that the shape of lipid electropores in
      living cell membranes may be asymmetric. We describe here the axially asymmetric
      pores that form when mechanical constraints are applied to selected phospholipid
      atoms. Electropore formation proceeds even with severe constraints in place, but
      pore shape and pore formation time are affected. Since lateral and transverse
      movement of phospholipids may be restricted in cell membranes by covalent
      attachments to or non-covalent associations with other components of the membrane
      or to membrane-proximate intracellular or extracellular biomolecular assemblies,
      these lipid-constrained molecular models point the way to more realistic
      representations of cell membranes in electric fields.

PMID- 29170843
TI  - The impact of waiting for intervention on costs and effectiveness: the case of
      transcatheter aortic valve replacement.
AB  - OBJECTIVES: The economic crisis in Europe might have limited access to some
      innovative technologies implying an increase of waiting time. The purpose of the
      study is to evaluate the impact of waiting time on the costs and benefits of
      transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic
      stenosis. METHODS: This is a cost-utility analysis from the perspective of the
      Spanish National Health Service. Results of two prospective hospital registries
      (158 and 273 consecutive patients) were incorporated into a probabilistic Markov
      model to compare quality adjusted life years (QALYs) and costs for TAVR after
      waiting for 3-12 months, relative to immediate TAVR. We simulated a cohort of
      1000 patients, male, and 80 years old; other patient profiles were assessed in
      sensitivity analyses. RESULTS: As waiting time increased, costs decreased at the
      expense of lower survival and loss of QALYs, leading to incremental cost
      effectiveness ratios for eliminating waiting lists of about 12,500 ? per QALY. In
      subgroup analyses prioritization of patients for whom higher benefit was expected
      led to a smaller loss of QALYs. Concerning budget impact, long waiting lists
      reduced spending considerably and permanently. CONCLUSIONS: A shorter waiting
      time is likely to be cost-effective (considering commonly accepted willingness-to
      pay thresholds in Europe) relative to 3 months or longer waiting periods. If
      waiting lists are nevertheless seen as unavoidable due to severe but temporary
      budgetary restrictions, prioritizing patients for whom higher benefit is expected
      appears to be a way of postponing spending without utterly sacrificing patients'
      survival and quality of life.

PMID- 29170845
TI  - Trapping and resection of cortical MCA mycotic aneurysm in eloquent area.
AB  - BACKGROUND: Mycotic aneurysms, although well recognized, are relatively rare
      intracranial vascular pathology. These aneurysms are typically located in distal
      cortical vessels. When these aneurysms are located in eloquent cerebral
      territories, they may become challenging to treat. Eloquent location may
      necessitate intraoperative angiographic evaluation to verify complete aneurysmal
      occlusion/obliteration and preservation of normal adjacent vasculture. Recently,
      ICG videoangiography has become a widely used intra-operative adjunct and is an
      important tool used to assess complete occlusion and vessel patency at the
      conclusion of clip reconstruction. In this report, we outline the comprehensive
      and concurrent utilization of both vascular imaging modalities to ensure safe and
      complete occlusion of a mycotic aneurysm. METHODS: We describe our experience
      with a patient with left M4, Rolandic, enlarging mycotic aneurysm that was
      treated in a comprehensive fashion with microsurgery and intra-operative
      angiography (IA). CONCLUSIONS: ICG videoangiography, in combination with
      concurrent intraoperative angiography in the setting of complex vascular lesions,
      may support intraoperative decision-making and provide demonstration of complete
      occlusion in an immediate fashion. A hybrid operative suite allows for high
      quality imaging confirming complete resection.

PMID- 29170844
TI  - Early recognition of aggressive pituitary adenomas: a single-centre experience.
AB  - BACKGROUND: Pituitary adenomas are usually considered benign tumours, although
      some of them can exhibit an aggressive behaviour. Patients with clinically
      aggressive pituitary adenomas are frequently diagnosed with larger masses, and
      may present an earlier recurrence (or persistence) after surgery. Our aim was to
      characterise the clinical, histopathological and radiological features of
      patients with aggressive pituitary adenoma, in order to correlate their clinical
      behaviour with the response to treatment plan. METHOD: We considered an
      aggressive pituitary adenoma on the basis of radiological features (size, local
      invasion), pathological reports (atypical adenoma: MIB-1 >3%, p53
      immunoreactivity, increased mitotic activity) and clinical aspects (response to
      surgery, radiotherapy and medical treatment). RESULTS: Among our cohort of 582
      patients, we considered 102 subjects with aggressive pituitary adenomas (18%, 56
      male and 46 female): 14 adrenocorticotrophic hormone (ACTH)-secreting, 18 growth
      hormone (GH)-secreting, 23 prolactin (PRL)-secreting and 47 non-secreting, with a
      median follow-up of 5 years. In the whole cohort, 75% of patients with aggressive
      pituitary adenomas presented invasion of surrounding structure, especially GH
      secreting, PRL-secreting and non-secreting. Besides invasion, their remission
      rate after surgery, radiotherapy or medical treatment was similar, irrespective
      of hormonal secretion. Surgery was the most performed treatment (overall
      remission rate of 24%), especially in those patients with ACTH- or GH-secreting
      adenoma, and 22% of patients were submitted to radiotherapy, with a remission
      rate of 45% after a median of 3 years. Two consecutive years of medical
      treatment, in patients with secreting pituitary adenoma, achieved disease control
      in 41% of them. Considering pathological reports, 24% of cases were defined as
      atypical adenomas; radiological characteristics, responses to medical treatment
      and remission rates were similar among patients with typical and atypical
      adenoma. CONCLUSIONS: We proposed a new and comprehensive definition of
      aggressive pituitary adenoma, based upon radiological, clinical and pathological
      features. In a selected cohort of patients, radiological invasion resulted in the
      most common marker to describe the aggressive behaviour of pituitary adenoma.
      Surgery, radiotherapy and medical treatment (the latter only in secreting
      adenoma) achieved disease control in half of the patients with aggressive
      adenoma, especially surgery in those with ACTH-oma and medical treatment in those
      with GH- and PRL-secreting adenoma. Nevertheless, radiological, clinical or
      atypical features did not affect the outcome.

PMID- 29170846
TI  - Letter to the editor of Acta Neurochirurgica: simultaneous pericranial and
      nasoseptal "double-flap" reconstruction after combined transcranial and
      endoscopic endonasal resection of anterior skull base tumors.

PMID- 29170848
TI  - Isolated bilateral internuclear ophthalmoplegia due to lacunar infarction.

PMID- 29170849
TI  - MYH7 mutation associated with two phenotypes of myopathy.
AB  - The mutations of MYH7 (slow skeletal/beta-cardiac myosin heavy chain) are
      commonly found in familial hypertrophic/dilated cardiomyopathy, and also can
      cause Laing early-onset distal myopathy (LDM), myosin storage myopathy (MSM), and
      congenital myopathy with fiber-type disproportion (CFTD). Here we report two
      cases whose diagnosis was hereditary myopathy according to clinical feature and
      muscle pathology analysis. High-throughput genomic sequencing (next generation
      sequencing) was performed to validate the diagnosis. Two MYH7 mutations, p.R1845W
      and p.E1687del, were identified. p.R1845W was found in a male patient showing
      weakness of both terminal lower legs without foot drop. Muscle pathology
      stainings characteristically showed the hyaline body in the intracytoplasmic
      location. The novel mutation p.E1687del was found in a family with seven
      patients. The proband showed foot drop, scoliosis, and winged scapula, while his
      mother only showed mild foot drop and winged scapula. Muscle pathology analysis
      showed congenital centronucleus myopathy. Both cases only showed muscular
      disorder and had no cardiomyopathy. This study, for the first time, reports the
      MYH7 mutations associated with centronucleus myopathy.

PMID- 29170850
TI  - Carbon monoxide inhibits hemotoxic activity of Elapidae venoms: potential role of
      heme.
AB  - Envenomation by hemotoxic enzymes continues to be a major cause of morbidity and
      mortality throughout the world. With regard to treatment, the gold standard to
      abrogate coagulopathy caused by these venoms is still the administration of
      antivenom; however, despite antivenom therapy, coagulopathy still occurs and
      recurs. Of interest, this laboratory has demonstrated in vitro and in vivo that
      coagulopathy inducing venom derived from snakes of the family Viperidae exposed
      to carbon monoxide (CO) is inhibited, potentially by an attached heme. The
      present investigation sought to determine if venoms derived from snakes of the
      Elapidae family (taipans and cobras) could also be inhibited with CO or with the
      metheme inducing agent, O-phenylhydroxylamine (PHA). Assessing changes in
      coagulation kinetics of human plasma with thrombelastography, venoms from
      Elapidae snakes were exposed in isolation to CO (five species) or PHA (one
      specie) and placed in human plasma to assess changes in procoagulant or
      anticoagulant activity. The procoagulant activity of two taipan venoms and
      anticoagulant activity of three cobra venoms were significantly inhibited by CO.
      The venom of the inland taipan was also inhibited by PHA. In sum, these data
      demonstrate indirectly that the biometal heme is likely bound to these disparate
      venoms as an intermediary modulatory molecule. In conclusion, CO may not just be
      a potential therapeutic agent to treat envenomation but also may be a potential
      modulator of heme as a protective mechanism for venomous snakes against injury
      from their own proteolytic venoms.

PMID- 29170851
TI  - The complete chloroplast genome sequence of Dodonaea viscosa: comparative and
      phylogenetic analyses.
AB  - The plant chloroplast (cp) genome is a highly conserved structure which is
      beneficial for evolution and systematic research. Currently, numerous complete cp
      genome sequences have been reported due to high throughput sequencing technology.
      However, there is no complete chloroplast genome of genus Dodonaea that has been
      reported before. To better understand the molecular basis of Dodonaea viscosa
      chloroplast, we used Illumina sequencing technology to sequence its complete
      genome. The whole length of the cp genome is 159,375 base pairs (bp), with a pair
      of inverted repeats (IRs) of 27,099 bp separated by a large single copy (LSC)
      87,204 bp, and small single copy (SSC) 17,972 bp. The annotation analysis
      revealed a total of 115 unique genes of which 81 were protein coding, 30 tRNA,
      and four ribosomal RNA genes. Comparative genome analysis with other closely
      related Sapindaceae members showed conserved gene order in the inverted and
      single copy regions. Phylogenetic analysis clustered D. viscosa with other
      species of Sapindaceae with strong bootstrap support. Finally, a total of 249
      SSRs were detected. Moreover, a comparison of the synonymous (Ks) and
      nonsynonymous (Ka) substitution rates in D. viscosa showed very low values. The
      availability of cp genome reported here provides a valuable genetic resource for
      comprehensive further studies in genetic variation, taxonomy and phylogenetic
      evolution of Sapindaceae family. In addition, SSR markers detected will be used
      in further phylogeographic and population structure studies of the species in
      this genus.

PMID- 29170853
TI  - Brain Networks are Independently Modulated by Donepezil, Sleep, and Sleep
      Deprivation.
AB  - Resting-state connectivity has been widely studied in the healthy and
      pathological brain. Less well-characterized are the brain networks altered during
      pharmacological interventions and their possible interaction with vigilance. In
      the hopes of finding new biomarkers which can be used to identify cortical
      activity and cognitive processes linked to the effects of drugs to treat
      neurodegenerative diseases such as Alzheimer's disease, the analysis of networks
      altered by medication would be particularly interesting. Eleven healthy subjects
      were recruited in the context of the European Innovative Medicines Initiative
      'PharmaCog'. Each underwent five sessions of simultaneous EEG-fMRI in order to
      investigate the effects of donepezil and memantine before and after sleep
      deprivation (SD). The SD approach has been previously proposed as a model for
      cognitive impairment in healthy subjects. By applying network based statistics
      (NBS), we observed altered brain networks significantly linked to donepezil
      intake and sleep deprivation. Taking into account the sleep stages extracted from
      the EEG data we revealed that a network linked to sleep is interacting with sleep
      deprivation but not with medication intake. We successfully extracted the
      functional resting-state networks modified by donepezil intake, sleep and SD. We
      observed donepezil induced whole brain connectivity alterations forming a network
      separated from the changes induced by sleep and SD, a result which shows the
      utility of this approach to check for the validity of pharmacological resting
      state analysis of the tested medications without the need of taking into account
      the subject specific vigilance.

PMID- 29170854
TI  - Why childhood-onset type 1 diabetes impacts labour market outcomes: a mediation
      analysis.
AB  - AIMS/HYPOTHESIS: Previous studies show a negative effect of type 1 diabetes on
      labour market outcomes such as employment and earnings later in life. However,
      little is known about the mechanisms underlying these effects. This study aims to
      analyse the mediating role of adult health, education, occupation and family
      formation. METHODS: A total of 4179 individuals from the Swedish Childhood
      Diabetes Register and 16,983 individuals forming a population control group born
      between 1962 and 1979 were followed between 30 and 50 years of age. The total
      effect of having type 1 diabetes was broken down into a direct effect and an
      indirect (mediating) effect using statistical mediation analysis. We also
      analysed whether type 1 diabetes has different effects on labour market outcome
      between the sexes and across socioeconomic status. RESULTS: Childhood-onset type
      1 diabetes had a negative impact on employment (OR 0.68 [95% CI 0.62, 0.76] and
      OR 0.76 [95% CI 0.67, 0.86]) and earnings (-6%, p < 0.001 and -8%, p < 0.001) for
      women and men, respectively. Each of the mediators studied contributed to the
      total effect with adult health and occupational field accounting for the largest
      part. However, some of the effect could not be attributed to any of the mediators
      studied and was therefore likely related to other characteristics of the disease
      that hamper career opportunities. The effect of type 1 diabetes on employment and
      earnings did not vary significantly according to socioeconomic status of the
      family (parental education and earnings). CONCLUSIONS/INTERPRETATION: A large
      part of the effect of type 1 diabetes on the labour market is attributed to adult
      health but there are other important mediating factors that need to be considered
      to reduce this negative effect.

PMID- 29170855
TI  - Laparoscopic and robotic surgery for stone disease.
AB  - Treatment for stone disease has evolved drastically during the past 3-4 decades.
      Ureteroscopy, percutaneous nephrolithotomy along with SWL, provides the means to
      treat practically all urinary tract stones with minimal invasion to the patients.
      However, for complex stone case scenarios where open surgery is being considered,
      a less invasive and better tolerated option such as laparoscopy (robot assisted
      or not) can be performed. The present manuscript reviews role of laparoscopic and
      robotic surgery in treating urinary tract stones.

PMID- 29170852
TI  - T cell subsets: an integral component in pathogenesis of rheumatic heart disease.
AB  - Acute rheumatic fever (ARF) is a consequence of pharyngeal infection of group A
      streptococcal (GAS) infection. Carditis is the most common manifestation of ARF
      which occurs in 30-45% of the susceptible individuals. Overlooked ARF cases might
      further progress towards rheumatic heart disease (RHD) in susceptible
      individuals, which ultimately leads to permanent heart valve damage. Molecular
      mimicry between streptococcal antigens and human proteins is the most widely
      accepted theory to describe the pathogenesis of RHD. In the recent past, various
      subsets of T cells have been reported to play an imperative role in the
      pathogenesis of RHD. Alterations in various T cell subsets, viz. Th1, Th2, Th17,
      and Treg cells, and their signature cytokines influence the immune responses and
      are associated with pathogenesis of RHD. Association of other T cell subsets
      (Th3, Th9, Th22, and TFH) is not defined in context of RHD. Several
      investigations have confirmed the up-regulation of adhesion molecules and thus
      infiltration of T cells into the heart tissues. T cells secrete both Th type 1
      and type 2 cytokines and these auto-reactive T cells play a key role in
      progression of heart valve damage. In this review, we are going to discuss about
      the role of T cell subsets and their corresponding cytokines in the pathogenesis
      of RHD.

PMID- 29170856
TI  - Robot-assisted flexible ureteroscopy: an update.
AB  - The role of flexible ureteroscopy (FURS) in the management of nephrolithiasis has
      increased due to the improved armamentarium. However, FURS still represents a
      challenging technique limiting its diffusion. Similar to previous experiences in
      laparoscopy, recently developed robotic devices may significantly compensate for
      the ergonomic deficiencies of FURS. Based on a short description of the history
      of robotic devices for laparoscopy, this article summarizes all current
      developments of robotic FURS. In 2008, robotic FURS was first reported using the
      Sensei-Magellan system designed for interventional cardiology. However, with this
      device the ureteroscope was only passively manipulated, which represented the
      main reason why this project has been discontinued after 18 clinical cases.
      Avicenna RoboflexTM was especially developed for FURS. It consists of a surgeon's
      console and manipulator of a flexible ureterorenoscope. The console provides an
      adjustable seat with armrests and two manipulators of the endoscope: the right
      wheel enables deflection and the left horizontal joystick allows rotation as well
      as advancing and retracting the instrument. The speed of rotation and advancement
      can be regulated at the screen of the console. Using the IDEAL system for
      evaluation of new robotic devices, safety and efficacy of the system could be
      demonstrated in two multi-centric studies providing significant improved
      ergonomics for the surgeon (IDEAL stage 1 and 2). Future studies are necessary to
      determine the final role of robotic FURS.

PMID- 29170857
TI  - Comorbidities and medication use in patients with a recent clinical fracture at
      the Fracture Liaison Service.
AB  - : In this cross-sectional study, two-thirds of Fracture Liaison Service (FLS)
      patients had comorbidities and medications associated with increased bone- or
      fall-related fracture risk. Bone-related and fall-related fracture risk (BRR and
      FRR) were associated with age and fracture type, but not with gender or BMD.
      Systematic evaluation of these factors leads to a more profound assessment in FLS
      care. INTRODUCTION: This study is a systematic evaluation of comorbidities and
      medications associated with increased fracture risk in patients aged 50-90 years
      with a recent fracture visiting the FLS. METHODS: In this cross-sectional cohort
      study, comorbidities were classified according to ICD-10 and medications
      according to the Anatomic Therapeutic Chemical (ATC) classification and further
      categorized into those associated BRR and FRR. RESULTS: Of 1282 patients (72%
      women; 65 +/- 9 years), 53% had at least one BRR, 46% had at least one FRR, and
      66% at least one BRR and/or FRR. At least one BRR, as well as at least one FRR
      were associated with age, BMI, and fracture type, but not with gender or BMD. The
      proportion of patients with only BRR (+/- 20%) or only FRR (+/- 10%) was similar
      among ages, gender, BMI, fracture type, and BMD. The combination of at least one
      BRR and at least one FRR was significantly associated with age, BMI, and major
      fractures, but not with gender or BMD. CONCLUSION: Comorbidities and medications
      associated with increased fracture risk are present in two-thirds of patients
      visiting the FLS. In addition, the proportion of patients having a combination of
      BRR and FRR increased significantly with age, BMI, and fracture severity. This
      indicates that systematic evaluation of these factors is important for a more
      profound assessment of subsequent fracture risk in FLS care.

PMID- 29170858
TI  - Impact of choice of future climate change projection on growth chamber
      experimental outcomes: a preliminary study in potato.
AB  - Understanding the impacts of climate change on agriculture is essential to ensure
      adequate future food production. Controlled growth experiments provide an
      effective tool for assessing the complex effects of climate change. However, a
      review of the use of climate projections in 57 previously published controlled
      growth studies found that none considered within-season variations in projected
      future temperature change, and few considered regional differences in future
      warming. A fixed, often arbitrary, temperature perturbation typically was applied
      for the entire growing season. This study investigates the utility of employing
      more complex climate change scenarios in growth chamber experiments. A case study
      in potato was performed using three dynamically downscaled climate change
      projections for the mid-twenty-first century that differ in terms of the timing
      during the growing season of the largest projected temperature changes. The
      climate projections were used in growth chamber experiments for four elite potato
      cultivars commonly planted in Michigan's major potato growing region. The choice
      of climate projection had a significant influence on the sign and magnitude of
      the projected changes in aboveground biomass and total tuber count, whereas all
      projections suggested an increase in total tuber weight and a decrease in
      specific gravity, a key market quality trait for potato, by mid-century. These
      results demonstrate that the use of more complex climate projections that extend
      beyond a simple incremental change can provide additional insights into the
      future impacts of climate change on crop production and the accompanying
      uncertainty.

PMID- 29170859
TI  - Patients' Reported Usage of Weight Management Skills Following Bariatric Surgery.
AB  - Little is known about which specific weight management skills bariatric patients
      find most and least valuable. Participants completed a measure assessing their
      usage of weight management skills at a follow-up appointment one or more years
      after undergoing bariatric surgery. Decreased usage of skills was associated with
      unsuccessful weight outcome, defined as losing less than 50% of excess weight, as
      well as weight regain. Weighing regularly was the skill selected most often by
      successful participants as helpful, and was chosen by a significantly smaller
      percentage of unsuccessful participants and those who regained a clinically
      significant amount of weight. A majority of both successful and unsuccessful
      participants indicated that they had discontinued food journaling. Weighing
      regularly may be perceived as a more useful method of self-monitoring.

PMID- 29170860
TI  - gamma-Glutamyltransferase Fractions in Obese Subjects with Type 2 Diabetes:
      Relation to Insulin Sensitivity and Effects of Bariatric Surgery.
AB  - BACKGROUND/OBJECTIVES: Gamma-glutamyltranspeptidase (GGT) levels are an
      independent risk marker for the development of type 2 diabetes (T2DM). We
      investigated the relationship between the newly identified serum GGT fractions
      and glucose metabolism in obese subjects before and after bariatric surgery.
      SUBJECTS/METHODS: Twenty-nine T2DM subjects, wait-listed for Roux-en-Y gastric
      bypass (RYGB; n = 21) or laparoscopic sleeve gastrectomy (LSG; n = 8), received a
      5-h mixed meal test before (T0), 15 days (T15), and 1 year after surgery (T365).
      Insulin sensitivity was assessed by the OGIS index and beta-cell function by C
      peptide analysis; fractional GGT (b-, s-, m-, and f-GGT) analysis was performed
      by gel-filtration chromatography. RESULTS: At T15, total GGT activity decreased
      by 40% after LSG (p = 0.007) but remained unchanged after RYGB. At T365, all
      patients showed a reduction in total GGT, in particular b-GGT (>= 60%) and m-GGT
      (>= 50%). In patients with biopsy-proven steatohepatitis (n = 10), total, b-, s-,
      and m-GGT fractions at T0 were significantly higher than in patients with low
      grade steatosis (p = 0.016, 0.0003, and 0.005, respectively); at T365, there was
      a significant fall in total GGT as well as in each fraction in both groups. In a
      multiple regression model, b-GGT was the only fraction related to insulin
      sensitivity (p = 0.016; beta coeff. = - 14.0) independently of BMI, fasting
      glucose, and triglycerides. CONCLUSIONS: While GGT activity is generally
      associated with impaired glucose metabolism, fractional GGT analysis showed that
      the b-GGT fraction specifically and independently tracks with insulin resistance.

PMID- 29170861
TI  - Incidence of peripheral nerve injury during shoulder arthroplasty when motor
      evoked potentials are monitored.
AB  - To report the incidence of clinically detectable nerve injuries when utilizing
      transcranial electrical motor evoked potentials (MEPs) during shoulder
      arthroplasty. A retrospective review of patients undergoing shoulder arthroplasty
      with continuous IONM was performed. The criteria for nerve alerts was an 80%
      amplitude reduction in MEPs. The primary outcome measure was post-operative
      clinically detectable nerve deficit. An additional retrospective analysis on a
      subset of cases using an all-or-none (100% amplitude reduction) criterion applied
      to the deltoid was performed. Two hundred eighty four arthroplasty cases were
      included. There were no permanent post-operative nerve injuries and two transient
      nerve injuries (0.7%). MEP alerts occurred in 102 cases (36.2%). Nineteen (6.7%)
      cases did not have signals return above alert threshold at closure. These cases
      were significantly associated with post-operative nerve injury (p = 0.03). There
      were no false negatives, making sensitivity 100% and specificity was 93.9%. In
      the subset of cases in which an all-or-none criterion was retrospectively applied
      to just the deltoid, MEP alerts occurred in just 17.9% of cases; specificity
      improved to 98.0%. We conclude that utilization of the real-time diagnostic MEP
      data during shoulder arthroplasty aids surgeons in decision making regarding
      impending peripheral nerve injuries.

PMID- 29170862
TI  - Editorial on EMC 2017 special issue.

PMID- 29170863
TI  - Strontium Promotes Transforming Growth Factors beta1 and beta2 Expression in Rat
      Chondrocytes Cultured In Vitro.
AB  - The transforming growth factors beta1 (TGF-beta1) and TGF-beta2, as two distinct
      homodimers of TGF-beta superfamily, involve in chondrocyte growth and
      differentiation. Emerging evidence has implied that strontium (Sr) plays an
      important role in the bone formation and resorption, and has strong effects on
      stimulating human cartilage matrix formation in vitro. However, the direct
      effects of Sr on TGF-beta1 and TGF-beta2 expressions in chondrocytes are not
      entirely clear. The purpose of this study was to evaluate the influence of
      different Sr concentrations on the expression of TGF-beta1 and TGF-beta2 in rat
      chondrocytes in vitro. Chondrocytes were isolated from Wistar rat articular by
      enzymatic digestion. Strontium chloride hexahydrate (SrCl2.6H2O) was used as a Sr
      source in this study. Sr was added to the culture solution at final
      concentrations of 0, 0.5, 1.0, 2.0, 5.0, 20.0, and 100 MUg/mL. After 72 h of
      continuous culture, TGF-beta1 and TGF-beta2 mRNA abundance and protein expression
      levels in the chondrocytes were determined by real-time polymerase chain reaction
      (real-time PCR) and Western blot, respectively. The results showed that TGF-beta1
      and TGF-beta2 expressions in chondrocytes increased dose-dependently with Sr
      concentration. The mRNA abundance of TGF-beta1 and TGF-beta2 were markedly higher
      than those observed for control (P < 0.01) when the Sr-treated concentration
      exceeded 1.0 and 5.0 MUg/mL, respectively. The TGF-beta1 and TGF-beta2 protein
      expression levels were extremely significantly higher than those in the control
      group (P < 0.01) at above 5.0 MUg/mL Sr-treatment. These results indicated that
      Sr could involve in the chondrocytes metabolism via regulating TGF-beta1 and TGF
      beta2 signalling.

PMID- 29170864
TI  - Risk of Malignancy in a Nationwide Cohort of Elderly Inflammatory Bowel Disease
      Patients.
AB  - BACKGROUND: Management of elderly inflammatory bowel disease (IBD) patients (>=
      65 years of age) is complicated due to many factors, including a higher risk of
      cancer, which may impact therapeutic decisions. OBJECTIVE: The aim of this study
      was to determine the risk of cancer among elderly IBD patients compared with
      younger IBD patients. Additionally, the absolute risk of malignancy and factors
      contributing to it were evaluated, and therapeutic patterns among the elderly
      were assessed. METHODS: This retrospective cohort study extracted data from the
      Truven Health Analytics MarketScan(r) database. Among adult IBD patients who were
      free of cancer before starting on corticosteroids, immunomodulators, or
      biologics, a Cox model for time to cancer was fitted that adjusted for several
      covariates, including time-dependent treatment. Baseline results were evaluated
      by age group, as were the incidence of cancer and the distribution of cancer
      subtypes. RESULTS: The elderly IBD cohort (n = 8788) had a higher prevalence of
      cancer and several other ailments before starting treatment, relative to the
      younger IBD cohort aged 18-64 years (n = 54,971). During follow-up, the elderly
      IBD cohort experienced a higher incidence of malignancy, confirmed by a hazard
      ratio (HR) of 3.04 (95% confidence interval [CI] 2.71-3.41) from the Cox model
      fit. The risk of cancer was also significantly associated with male sex (HR 0.82
      female), duration of disease (HR 1.08), several comorbidities and corticosteroid
      use (HR 1.35), but not with the use of immunomodulators or biologics. Non
      Hodgkin's lymphoma, urinary tract malignancy, and prostate, lung, and female
      breast cancers were observed more commonly in this elderly IBD cohort when
      compared with the same age group in the Surveillance, Epidemiology, and End
      Results (SEER) database. CONCLUSIONS: The elderly with IBD have a higher risk of
      malignancy when compared with younger IBD patients and the general age-matched
      population, with certain cancers being more common among these patients.

PMID- 29170865
TI  - Deciding upon Transition to Residential Care for Persons Living with Dementia:
      why Do Iranian Family Caregivers Living in Sweden Cease Caregiving at Home?
AB  - Previous research has shown how filial piety is strong among people of Iranian
      background and that traditional Iranian culture result in most families'
      preferring to care for their elderly (and sick) family members at home. While
      acknowledging this, this article highlights what living in diaspora could mean in
      terms of cultural adaption and changing family values. By interviewing people
      with Iranian background living in Sweden (n = 20), whom all have been former
      primary caregivers to a relative living with dementia, we are able to show how
      the decision to cease caregiving at home is taken, and what underlying factors
      form the basis for such decision. Results indicate that although the existence of
      a Persian profiled dementia care facility is crucial in the making of the
      decision, it is the feeling of 'sheer exhaustion' that is the main factor for
      ceasing care at home. And, we argue, the ability to make such a decision based
      upon 'being too tired' must be understood in relation to transition processes and
      changes in lifestyle having an affect upon cultural values in relation to filial
      piety. Because, at the same time the changes on cultural values might not change
      accordingly among the elderly who are the ones moving into residential care,
      resulting in them quite often being left out of the actual decision.

PMID- 29170866
TI  - Registration of angiographic image on real-time fluoroscopic image for image
      guided percutaneous coronary intervention.
AB  - PURPOSE: In percutaneous coronary intervention (PCI), cardiologists must study
      two different X-ray image sources: a fluoroscopic image and an angiogram.
      Manipulating a guidewire while alternately monitoring the two separate images on
      separate screens requires a deep understanding of the anatomy of coronary vessels
      and substantial training. We propose 2D/2D spatiotemporal image registration of
      the two images in a single image in order to provide cardiologists with enhanced
      visual guidance in PCI. METHODS: The proposed 2D/2D spatiotemporal registration
      method uses a cross-correlation of two ECG series in each image to temporally
      synchronize two separate images and register an angiographic image onto the
      fluoroscopic image. A guidewire centerline is then extracted from the
      fluoroscopic image in real time, and the alignment of the centerline with vessel
      outlines of the chosen angiographic image is optimized using the iterative
      closest point algorithm for spatial registration. RESULTS: A proof-of-concept
      evaluation with a phantom coronary vessel model with engineering students showed
      an error reduction rate greater than 74% on wrong insertion to nontarget branches
      compared to the non-registration method and more than 47% reduction in the task
      completion time in performing guidewire manipulation for very difficult tasks.
      Evaluation with a small number of experienced doctors shows a potentially
      significant reduction in both task completion time and error rate for difficult
      tasks. The total registration time with real procedure X-ray (angiographic and
      fluoroscopic) images takes [Formula: see text] 60 ms, which is within the
      fluoroscopic image acquisition rate of 15 Hz. CONCLUSIONS: By providing
      cardiologists with better visual guidance in PCI, the proposed spatiotemporal
      image registration method is shown to be useful in advancing the guidewire to the
      coronary vessel branches, especially those difficult to insert into.

PMID- 29170867
TI  - A novel fabrication method of carbon electrodes using 3D printing and chemical
      modification process.
AB  - Three-dimensional (3D) printing is an emerging technique in the field of
      biomedical engineering and electronics. This paper presents a novel
      biofabrication method of implantable carbon electrodes with several advantages
      including fast prototyping, patient-specific and miniaturization without
      expensive cleanroom. The method combines stereolithography in additive
      manufacturing and chemical modification processes to fabricate electrically
      conductive carbon electrodes. The stereolithography allows the structures to be
      3D printed with very fine resolution and desired shapes. The resin is then
      chemically modified to carbon using pyrolysis to enhance electrochemical
      performance. The electrochemical characteristics of 3D printing carbon electrodes
      are assessed by cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS). The specific capacitance of 3D printing carbon electrodes is
      much higher than the same sized platinum (Pt) electrode. In-vivo electromyography
      (EMG) recording, 3D printing carbon electrodes exhibit much higher signal-to
      noise ratio (40.63 +/- 7.73) than Pt electrodes (14.26 +/- 6.83). The proposed
      biofabrication method is envisioned to enable 3D printing in many emerging
      applications in biomedical engineering and electronics.

PMID- 29170868
TI  - Levofloxacin for febrile neutropenia prophylaxis in acute myeloid leukemia
      patients associated with reduction in hospital admissions.
AB  - PURPOSE: The purpose of this study is to evaluate the efficacy and safety of
      prophylactic oral levofloxacin in acute myeloid leukemia (AML) patients after
      receiving consolidation chemotherapy to prevent febrile neutropenia. METHODS: We
      conducted a retrospective chart review of 50 AML patients who were prescribed
      levofloxacin and 50 AML patients who were not prescribed levofloxacin post
      consolidation chemotherapy between June 2006 and August 2013 at a tertiary
      academic medical center. The primary outcome of this study was to evaluate the
      effectiveness of levofloxacin in preventing hospital readmission due to febrile
      neutropenia. Secondary outcomes evaluated the safety of this therapy, including
      the rate of Clostridium difficile-associated diarrhea (CDAD) within 30 days from
      discharge of receiving consolidation chemotherapy and rate of fluoroquinolone
      resistance in positive bacterial cultures. RESULTS: Hospital readmission due to
      febrile neutropenia after the first consolidation cycle occurred in 42% of
      patients prescribed levofloxacin, as compared to 72% that were not prescribed
      levofloxacin (p = 0.002). This was also significantly reduced when levofloxacin
      was prescribed after all consolidation cycles (51.4 vs. 67%, p = 0.023). CDAD did
      not occur in any patient prescribed levofloxacin after the first cycle, compared
      to one case in those not prescribed levofloxacin. Evaluation of the impact on
      fluoroquinolone resistance was limited due to a paucity of fluoroquinolone
      susceptibilities reported. CONCLUSIONS: Prescribing oral levofloxacin post
      consolidation chemotherapy in AML patients is associated with a reduction in
      febrile neutropenia. Further research is required to identify the impact on
      fluoroquinolone resistance and risk of CDAD.

PMID- 29170869
TI  - Bilateral basal ganglia abscesses in infectious endocarditis: an uncommon
      complication.

PMID- 29170870
TI  - Physical restraint: time to let go.

PMID- 29170871
TI  - The diagnostic role of PTEN and ARID1A in serous effusions.
AB  - The aim of this study was to analyze the diagnostic role of PTEN and ARID1A in
      effusion cytology. Effusions (n = 279), consisting of 226 carcinomas (70 ovarian,
      64 breast, 36 lung, and 15 uterine corpus carcinomas; 41 carcinomas of other
      origin) and 53 malignant mesotheliomas, were analyzed for PTEN and ARID1A
      expression using immunohistochemistry. PTEN was preserved in 166 (59%) tumors,
      partially lost in 38 (14%), and absent in 75 (27%), with lower expression in
      malignant mesotheliomas compared to carcinomas, though not significantly (p =
      0.084). ARID1A was preserved in 243 (88%) tumors, partially lost in 18 (6%), and
      absent in 18 (6%). The majority of tumors with absent ARID1A were ovarian
      carcinomas, predominantly of clear cell or low-grade serous type. Reactive
      mesothelial cells in carcinoma specimens were uniformly positive for both
      proteins. ARID1A mutation analysis showed no mutations in eight analyzed
      specimens negative by immunohistochemistry. Loss of PTEN and ARID1A expression is
      highly specific for malignancy in effusion pathology. Loss of PTEN is not
      informative of organ of origin, whereas absence of ARID1A should raise suspicion
      of an ovarian primary.

PMID- 29170872
TI  - New insights from molecular phylogenetics of amoebophagous fungi (Zoopagomycota,
      Zoopagales).
AB  - Amoebophagous fungi are represented in all fungal groups: Basidiomycota,
      Ascomycota, Zygomycota, and Chytridiomycota. The amoebophagous fungi, within the
      zygomycota (Zoopagales, Zoopagomycota), mainly affect naked amoebae as
      ectoparasites or endoparasites. It is rather difficult to isolate members of the
      Zoopagales, because of their parasitic lifestyle, and to bring them into culture.
      Consequently, gene sequences of this group are undersampled, and its species
      composition and phylogeny are relatively unknown. In the present study, we were
      able to isolate amoebophagous fungi together with their amoeba hosts from various
      habitats (moss, pond, bark, and soil). Altogether, four fungal strains belonging
      to the genera Acaulopage and Stylopage plus one unidentified isolate were
      detected. Sequences of the 18S rDNA and the complete ITS region and partial 28S
      (LSU) rDNA were generated. Subsequent phylogenetic analyses showed that all new
      isolates diverge at one branch together with two environmental clonal sequences
      within the Zoopagomycota. Here, we provide the first molecular characterization
      of the genus Stylopage. Stylopage is closely related to the genus Acaulopage. In
      addition, taxonomy and phylogeny of amoebophagous fungi and their ecological
      importance are reviewed based on new sequence data, which includes environmental
      clonal sequences.

PMID- 29170873
TI  - Multispecies blow fly myiasis combined with hypothermia in a man assumed to be
      dead.
AB  - We describe the case of a man who was found with severe hypothermia and advanced
      myiasis involving five species of blow flies, which eventually led to a
      transtibial amputation of the man's right leg. A case of such a heavy and species
      rich infestation with fly larvae in an urban environment is extraordinary and
      has, to our knowledge, never been described so far. Best practice in cases such
      as this one demands accurate species identification not only to ensure
      appropriate treatment and pest management but also, from a forensic point of
      view, to explore the possibility of third-party responsibility. The cooperation
      between physicians and forensic entomologists is highlighted.

PMID- 29170874
TI  - Daily variation of NTBC and its relation to succinylacetone in tyrosinemia type 1
      patients comparing a single dose to two doses a day.
AB  - INTRODUCTION: In hereditary tyrosinemia type 1 (HT1) patients, the dose of NTBC
      that leads to the absence of toxic metabolites such as succinylacetone (SA) is
      still unknown. Therefore, the aims of this study were to investigate the
      variation and concentrations of 2-(2-nitro-4-trifluormethyl-benzyl)-1,3
      cyclohexanedione (NTBC) during the day in relation to the detection of SA, while
      comparing different dosing regimens. METHODS: All patients were treated with NTBC
      (mean 1.08 +/- 0.34 mg/kg/day) and a low phenylalanine-tyrosine diet. Thirteen
      patients received a single dose of NTBC and five patients twice daily. Home
      bloodspots were collected four times daily for three consecutive days measuring
      NTBC and SA concentrations. Statistical analyses were performed by using mixed
      model analyses and generalized linear mixed model analyses to study variation and
      differences in NTBC concentrations and the correlation with SA, respectively.
      RESULTS: NTBC concentrations varied significantly during the day especially if
      NTBC was taken at breakfast only (p = 0.026), although no significant difference
      in NTBC concentrations between different dosing regimens could be found (p =
      0.289). Momentary NTBC concentrations were negatively correlated with SA (p <
      0.001). Quantitatively detectable SA was only found in subjects with once daily
      administration of NTBC and associated with momentary NTBC concentrations <44.3
      MUmol/l. DISCUSSION: NTBC could be less stable than previously considered, thus
      dosing NTBC once daily and lower concentrations may be less adequate. Further
      research including more data is necessary to establish the optimal dosing of
      NTBC.

PMID- 29170875
TI  - Long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in
      fibrinolytic-treated STEMI patients undergoing early PCI.
AB  - The long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in
      patients undergoing early percutaneous coronary intervention (PCI) after
      fibrinolytic therapy is unknown. From May 2014 to August 2016, 212 patients
      undergoing PCI within 24 h of Tenecteplase (TNK), Aspirin, and Clopidogrel for ST
      elevated myocardial infarction (STEMI) were randomized at four Canadian sites to
      receive additional Clopidogrel or Ticagrelor initiated prior to PCI. The platelet
      reactivity units (PRU) were measured with the VerifyNow Assay before study drug
      administration (baseline), at 4 and 24 h post PCI, and follow-up appointment. A
      mixed-model analysis with time as the repeated measure and drug as the between
      subjects factor was calculated using 2 separate 1 * 4 ANOVAs, with students t
      tests used to compare drugs within each time point. Complete clinical follow-up
      data (median 115.0 days; IQR 80.3-168.8) was available in 50 patients (23.6%)
      randomized to either Clopidogrel (n = 23) or Ticagrelor (n = 27). Analyses
      revealed significant decreases in PRU from baseline to 4 h (261.4 vs. 71.7; Mdiff
      = - 189.7; p < 0.001) to 24 h (71.7 vs. 27.7; Mdiff = - 44.0; p < 0.001) to end
      of follow-up (27.7 vs.17.9; Mdiff = - 9.9. p = 0.016) for those randomized to
      Ticagrelor and significant decreases in PRU only from baseline to 4 h (271.3 vs.
      200.8; Mdiff = - 70.5, p = < 0.001) in patients receiving Clopidogrel, and a
      significantly greater proportion of patients with adequate platelet inhibition
      (PRU < 208) on long-term follow-up (Clopidogrel, 82.6% vs. Ticagrelor, 100.0%; p
      = 0.038). Our results demonstrate that in patients undergoing PCI within 24 h of
      fibrinolysis for STEMI, Ticagrelor provides prolonged platelet inhibition
      compared with Clopidogrel.

PMID- 29170876
TI  - Venous thromboembolism in assisted reproductive technologies: comparison between
      unsuccessful versus successful cycles in an Italian cohort.
AB  - Pregnancies after assisted reproductive technologies (ART) have been associated
      with an increased risk of venous thromboembolism (VTE). On the contrary, the
      magnitude of this risk in unsuccessful ART cycles (not resulting in a clinical
      pregnancy) has not yet been clearly defined. In this study, we evaluated the
      incidence of VTE in unsuccessful cycles and compared it with that recorded in
      successful cycles in the same study population. From a cohort of 998 women
      consecutively referred by local Fertility Clinics to our Atherosclerosis and
      Thrombosis Unit (April 2002-July 2011), we identified and included women with at
      least one cycle of ovarian stimulation and a negative history for VTE. Overall,
      661 women undergone 1518 unsuccessful and 318 successful cycles of ovarian
      stimulation, respectively, were analysed. VTE events occurred in 2/1518 (1.30/00)
      unsuccessful cycles compared with 3/318 (9.40/00) successful cycles, (Two-tailed
      Fisher exact test, p = 0.04, OR 0.14, 95% CI 0.02-1.02). Both cases observed in
      unsuccessful cycles were isolated pulmonary embolism occurred after OHSS; no
      antithrombotic prophylaxis had been prescribed. At logistic regression analysis,
      the occurrence of successful cycle and BMI were significantly and independently
      associated with the occurrence of VTE with an OR of 13.94 (95% CI 1.41-137.45)
      and 1.23 (95% CI 1.01-1.49), respectively. VTE incidence is significantly lower
      in unsuccessful cycles as compared to that of successful ones. However, although
      rare, thrombotic risk during ovarian stimulation cannot be excluded and, when it
      occurs, can be life-threatening. Therefore, particular attention should be paid
      to these women, independently of ART outcome.

PMID- 29170877
TI  - Oral anticoagulant dosing, administration, and storage: a cross-sectional survey
      of Canadian health care providers.
AB  - Direct oral anticoagulant (DOAC) use is increasing worldwide. However, if not
      taken or prescribed correctly, DOACs have serious side effects. It is crucial
      that healthcare providers (HCPs) offer patients accurate information and
      counselling around DOACs, to optimize safe and effective use. To assess knowledge
      around oral anticoagulant indication, dosing, storage, and administration, an
      electronic survey was distributed to HCPs across Canada from June to August 2017,
      with 18 questions on the practical use of oral anticoagulants. A total of 191
      responses were received: 100 from nurse practitioners, 42 from pharmacists, 27
      from Hematologists, 5 from Thrombosis specialists, 4 from internists, 9 from
      residents and fellows, and 2 each from family physicians and registered nurses.
      Only 51 (26.7%) of the respondents correctly identified all the approved
      indications for warfarin and 4 DOACs. Only 101 (52.9%) correctly identified that
      DOACs are not approved for treatment of heparin-induced thrombocytopenia,
      cerebral sinus venous thrombosis, or mechanical prosthetic valves. 112 (58.6%)
      felt comfortable or very comfortable prescribing oral anticoagulants. Half of the
      respondents knew that dabigatran should not be crushed, however only 85 (44.5%)
      knew that it should not be exposed to moisture. 94 (49%) knew that higher dose
      rivaroxaban should be taken with food. The results of our study demonstrate that
      there are important knowledge gaps around HCPs' practical understanding of oral
      anticoagulants. Future research should focus on educational interventions to
      improve HCPs' knowledge around indications, dosing, storage, and administration,
      with the goal of enhancing patient safety.

PMID- 29170878
TI  - Addressing Relationship Health Needs in Primary Care: Adapting the Marriage
      Checkup for Use in Medical Settings with Military Couples.
AB  - The overall objective of this study was to pilot the Marriage Checkup (MC), a
      brief intervention for enhancing marital resiliency tailored to a military
      population, for use by internal behavioral health consultants (IBHCs) working in
      an integrated primary care clinic. The MC was revised to fit into the fast-paced
      environment of primary care (e.g., streamlined to fit within three 30-min
      appointments), and military-relevant material was added to the content. IBHCs
      working in primary care were then trained to offer the intervention. Thirty
      participants were enrolled in the study and completed a relationship checkup and
      one-month follow-up questionnaires. Analysis of post-test and one-month follow-up
      data showed statistically significant improvements in participants' marital
      health compared to pre-treatment. The MC intervention appeared to be well
      received by both couples and IBHCs.

PMID- 29170879
TI  - Factors influencing recurrence and progression of Dupuytren's disease treated by
      Collagenase Clostridium histolitycum.
AB  - AIM OF THE STUDY: The purpose of this study was to determine the recurrence rate,
      possible adverse reactions and factors influencing recurrence and progression of
      Dupuytren's disease (DD) treated with Collagenase from Clostridium histolyticum
      (CCH). METHOD: This was a prospective study of 71 patients with DD treated with
      CCH from 2011 to February 2013, with a minimum follow-up period of four years.
      Clinical, functional, patient satisfaction, drug safety and factors influencing
      recurrence and disease progression were evaluated. RESULTS: In all patients, the
      rupture of the cord was achieved after the injection, reducing joint contracture.
      In five patients (7%) we verified the existence of disease recurrence during the
      follow-up. In 11 patients (15.5%) there was a disease progression. Three patients
      have been surgically operated on, without added surgery difficulty; the rate of
      recurrence and progression was higher in grades III and IV of Tubiana, in
      proximal interphalangeal (PIP) punctures, and was earlier in patients younger
      than 60 years. DISCUSSION: No serious local complications or general
      complications were observed with this method. The recurrence of DD, following
      criteria of Felici, is mainly observed in young patients with greater severity of
      the disease and at the PIP level. Progression is influenced by the same factors.
      Patients operated on after recurrence have no added difficulty in the surgical
      technique, as it has also been published in other studies. CONCLUSIONS: Patients
      with the lowest rates of recurrence and progression were those with a single cord
      in the metacarpophalangeal (MCP), a grade II of Tubiana, and were older than 60
      years.

PMID- 29170880
TI  - Fingernail and toenail clippings as a non-invasive measure of chronic cortisol
      levels in adult cancer survivors.
AB  - PURPOSE: Cancer survivors are at greater risk of comorbidities and functional
      decline due to physiological and psychological stress which can be measured by
      salivary cortisol. If saliva is used, multiple samples must be collected to
      accurately quantify long-term stress; however, fingernail (FN) and toenail (TN)
      clippings offer an opportunity to measure retrospective cortisol levels in a non
      invasive manner. METHODS: Three sets of FN and TN clippings were collected at 12
      month intervals in conjunction with saliva samples from cancer survivors (n =
      109) participating in two clinical trials. FN and TN samples were stored at room
      temperature (RT); a subset underwent additional processing and freezing before
      analysis. Cortisol levels were determined via enzyme immunoassay, and correlation
      coefficients were generated to determine overall correspondence of the individual
      measures. RESULTS: Matched RT and frozen samples were highly correlated for TN (r
      = 0.950, p = 5.44 * 10-37) and FN (r = 0.784, p = 1.05 * 10-10). Correlations
      between RT FN and TN were statistically significant (r = 0.621, p = 3.61 * 10-
      17), as were frozen FN and TN (r = 0.310, p = 0.0283). RT, but not frozen TN and
      FN correlated with salivary cortisol (r = 0.580, p = 1.65 * 10- 16 and r = 0.287,
      p = 0.00042 for TN and FN, respectively). CONCLUSIONS: FN and TN cortisol levels
      correlate with salivary cortisol in adult cancer survivors and may offer a less
      invasive and convenient means for measuring chronic cortisol levels.

PMID- 29170881
TI  - Factors related to longitudinal adherence in colorectal cancer screening:
      qualitative research findings.
AB  - BACKGROUND: The effectiveness of screening in colorectal cancer prevention
      depends on sustained participation rates. The objective of this study was to
      explore factors related to the longitudinal adherence of screening behavior in
      the context of a biennial population-based cancer screening program. METHODS:
      Eight focus groups were conducted with individuals who were invited two or three
      consecutive times to a population-based colorectal cancer screening program using
      a fecal occult blood test and who agreed to participate in the program at least
      once (n = 45). The criteria used to select the study members included adherence
      to fecal occult blood test maintenance, factors regarding their initial
      participation in the colorectal cancer screening, sex, and contextual educational
      level. RESULTS: The participants expressed a high level of satisfaction with the
      program; however, they showed a low level of understanding with respect to cancer
      screening. Consulting a general practitioner was cited by all participants as an
      important factor that mediated their final decision or influenced their behavior
      as a whole with regard to the program. Fear played a different role in the
      screening behavior for regular and irregular adherent participants. In the
      adherent participants, fear facilitated their continued participation in the
      screening program, whereas for the irregular participants, fear led them to avoid
      or refuse further screening. Having a close person diagnosed with colorectal
      cancer was a facilitator for the regular adherent participants. The irregular
      adherent participants showed some relaxation with respect to screening after a
      negative result and considered that further screening was no longer necessary.
      CONCLUSION: Considering the importance of primary healthcare professionals in the
      decision regarding sustained participation, it is important to better engage them
      with cancer screening programs, as well as improve the communication channels to
      provide accurate and balanced information for both health professionals and
      individuals.

PMID- 29170882
TI  - The association of unemployment with glucose metabolism: a systematic review and
      meta-analysis.
AB  - OBJECTIVES: Unemployment has been linked with poor health. We hypothesized that
      being unemployed is associated with disorders of glucose metabolism and performed
      a systematic review and meta-analysis of the literature to ascertain the
      relationship. METHODS: We searched the databases of Scopus, Medline Ovid and Web
      of Science for population-based original studies for past 20 years. Random
      effects meta-analyses were used to estimate odds ratios (OR) with 95% confidence
      intervals (CI) for prediabetes and type 2 diabetes among the unemployed as
      compared to those employed, separately for men and women when possible. RESULTS:
      Out of 981 articles found, 12 articles were included in the systematic review and
      eight articles in the meta-analyses. Unemployment was associated with 1.6-fold
      odds for prediabetes (OR 1.58; 95% CI 1.07-2.35), and 1.7-fold odds for type 2
      diabetes (OR 1.72; 95% CI 1.14-2.58) in the total sample. The corresponding
      associations for type 2 diabetes were also found stratified for men (OR 1.53; 95%
      CI 1.47-1.60) and women (OR 1.60; 95% CI 1.33-1.92). CONCLUSIONS: Unemployment is
      associated with prediabetes and type 2 diabetes, global concerns of public health
      with potential for prevention.

PMID- 29170883
TI  - Identification of key gene modules and pathways of human breast cancer by co
      expression analysis.
AB  - BACKGROUND: Breast cancer is the most common and aggressive tumor causing injury
      to women world wide. Although gene expression analysis had been performed
      previously, systemic co-expression analysis for this cancer is still lacking to
      date. We attempted to identify the critical modules of breast cancer. METHODS: Co
      expression modules were established with the help of WGCNA and the interactions
      among them were performed by R language. Biological process and pathways analysis
      of co-expression genes were figured out by GO and KEGG functional enrichment
      analysis using DAVID dataset. RESULTS: In this study, expression data of 4,000
      genes from 136 samples with breast cancer was used for the establishment of co
      expression modules. And nine modules were identified. There was much higher scale
      independence among different modules by interactions analysis. Moreover, there
      was an obvious difference in adjacency degree among different modules. The most
      enriched pathways as immune response and ubiquitin-mediated proteolysis were
      identified as the most critical modules of breast cancer by GO and KEGG
      enrichment analysis. CONCLUSION: Our result demonstrated that immune response and
      ubiquitin-mediated proteolysis could serve as prognostic and predictive markers
      for the occurrence of breast cancer, providing evidence for further analysis in
      the prognosis and treatment of breast cancer.

PMID- 29170884
TI  - Is retrograde blood flow of aortic isthmus useful for the prenatal screening of
      coarctation of the aorta by fetal color Doppler echocardiography? A preliminary
      study.
AB  - PURPOSE: To validate the relationship between retrograde blood flow in the aortic
      isthmus (AoI-R) by color Doppler in fetal echocardiography and postnatal
      coarctation of the aorta (CoA) diagnosed as isthmus narrowing. METHODS: This was
      a retrospective study of 22 cases of prenatally suspected simple CoA or CoA with
      small ventricular septum defect based on fetal echocardiography performed by
      pediatric cardiologists in our hospital. Gestational age at the first detection
      of AoI-R and the optimal cut-off value for the prediction of postnatal CoA were
      mainly evaluated according to the postnatal diagnosis of CoA. RESULTS: All 22
      cases had AoI-R prenatally, and nine of them (40.9%) had isthmus narrowing and
      were diagnosed as having CoA immediately after birth. The gestational age at the
      first detection of AoI-R was significantly lower in cases with postnatal CoA than
      in those without (average 34.4 weeks; P = 0.034). The cut-off value for the
      prediction of postnatal CoA was 35.5 weeks of gestation, with a sensitivity and
      specificity of 77.8 and 69.2%, respectively. CONCLUSION: AoI-R determined by
      color Doppler echocardiography can become a useful tool in the screening of fetal
      CoA, especially at < 35 weeks of gestation.

PMID- 29170886
TI  - Phase II study of doxorubicin and thalidomide in patients with refractory
      aggressive fibromatosis.
AB  - Background To evaluate the efficacy and safety of doxorubicin (ADM) combined with
      thalidomide (THA) as a first-line treatment for patients with refractory
      aggressive fibromatosis (AF). Patients and Methods Eligible patients were treated
      with ADM 30 mg/m2 on days 1-2 and THA 200 mg nightly on days 1-21 every 3 weeks
      for a maximum of six cycles. THA was then continued for a total of 1 year. The
      primary end point was response rate (RR). Results Fifteen patients were enrolled
      in the study. No patient had a complete response, but five patients had partial
      responses, resulting in a RR of 33%. Eight patients (53%) had stable disease and
      two patients (13%) had progressive disease, and the disease control rate was 87%.
      The median progression free survival (mPFS) was 20.6 months (95% confidence
      interval, 14.5-26.7 months). Patients with below normal baseline serum albumin
      levels had significantly inferior mPFS compared with those with normal baseline
      serum albumin (1.4 months versus 23.7 months, P = 0.045). Grade 3/4 toxicities
      included leukopenia (33%), neutropenia (60%), febrile neutropenia (7%), nausea
      (7%), and vomiting (6.6%). Conclusions ADM plus THA was well-tolerated and
      effective as a first-line treatment for patients with refractory AF. However,
      patients with hypoalbuminemia at baseline had inferior clinical outcomes, and
      further studies are needed to investigate this issue.

PMID- 29170885
TI  - The structure of the S-layer of Clostridium difficile.
AB  - The nosocomially acquired pathogen Clostridium difficile is the primary causative
      agent of antibiotic associated diarrhoea and causes tens of thousands of deaths
      globally each year. C. difficile presents a paracrystalline protein array on the
      surface of the cell known as an S-layer. S-layers have been demonstrated to
      possess a wide range of important functions, which, combined with their inherent
      accessibility, makes them a promising drug target. The unusually complex S-layer
      of C. difficile is primarily comprised of the high- and low- molecular weight S
      layer proteins, HMW SLP and LMW SLP, formed from the cleavage of the S-layer
      precursor protein, SlpA, but may also contain up to 28 SlpA paralogues. A model
      of how the S-layer functions as a whole is required if it is to be exploited in
      fighting the bacterium. Here, we provide a summary of what is known about the S
      layer of C. difficile and each of the paralogues and, considering some of the
      domains present, suggest potential roles for them.

PMID- 29170888
TI  - Booming cancer immunotherapy fighting tumors.

PMID- 29170887
TI  - Early and late outcomes after open ascending aortic surgery: 47-year experience
      in a single centre.
AB  - The aims of the study are to describe the long-term survival of patients
      undergoing primary open ascending aortic surgery and to portray the evolution of
      aortic surgery during six decades in a single centre. Included were all 614
      patients who underwent primary ascending aortic surgery in 1968-2014 at one
      Nordic university hospital. Patients were identified and data were collected from
      patient records and surgical logs. Mortality data were acquired from the national
      registry. Median follow-up was 11.2 years using reverse Kaplan-Meier method.
      Overall 30-day survival was 91.2% and for 30-day survivor rates were 86.9, 77.6,
      52.1, 38.3 and 26.7% at 5, 10, 20, 30 and 40 years. There was no significant
      difference in long-term survival for 30-day survivors (p = 0.105) between
      patients treated emergently for dissection/rupture and electively (mainly
      ascending aortic aneurysms). On Cox regression era of surgery (p = 0.006),
      increasing age (p < 0.001) and indication (p < 0.001) were predictors of 30-day
      mortality. Arch involvement indicated twofold risk (HR 2.09, p = 0.05) compared
      to non-arch involved. Only increasing age (p < 0.001) predicted long-term
      mortality. There was a sixfold risk of 30-day mortality in the earliest era
      compared to the latest (p = 0.03). After the early postoperative phase following
      ascending aortic surgery, the surgical indication and urgency of the index
      operation have no significant impact on long-term survival. The very long term
      survival after ascending aortic surgery is excellent for 30-day survivors and
      improved through the era. Surgical treatment has improved and perioperative
      mortality has decreased significantly in 47 years.

PMID- 29170889
TI  - Transfer RNA-derived small RNAs in plants.
AB  - Rather than random degradation products, the 18 to 40 nucleotides (nt) transfer
      RNA-derived small RNAs (tsRNAs) are RNA species generated specifically from pre
      RNAs or mature tRNAs in archaea, bacteria and eukaryotes. Recent studies from
      animal systems have shown that tsRNAs are important non-coding RNAs that regulate
      gene expression at the transcriptional and/or post-transcriptional levels. They
      are involved in various biological processes, such as cell proliferation, tumor
      genesis, stress response and intergenerational epigenetic inheritance. In this
      review, we will summarize the discovery, biogenesis, and function of tsRNAs in
      higher plants. In addition, analysis on tsRNAs from lower plants is shown.

PMID- 29170890
TI  - CART trials are going ahead.

PMID- 29170891
TI  - AMPK and cardiac remodelling.
AB  - Cardiac remodelling is generally accepted as a critical process in the
      progression of heart failure. Myocyte hypertrophy, inflammatory responses and
      cardiac fibrosis are the main pathological changes associated with cardiac
      remodelling. AMP-activated protein kinase (AMPK) is known as an energy sensor and
      a regulator of cardiac metabolism under normal and ischaemic conditions.
      Additionally, AMPK has been shown to play roles in cardiac remodelling extending
      well beyond metabolic regulation. In this review, we discuss the currently
      defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on
      cardiac hypertrophy, inflammatory responses and fibrosis and the molecular
      mechanisms underlying these effects. In addition, we discuss some pharmacological
      activators of AMPK that are promising treatments for cardiac remodelling.

PMID- 29170892
TI  - Advancement in regional immunity and its clinical implication.
AB  - Organs in our body have formed their own unique immune surveillance system that
      is finely tuned by in situ milieu. Sequestrated tissue-resident immune cells
      differ from their counterparts in circulation and participate in tissue
      physiological activities and the maintenance of local homeostasis. Dysregulation
      of regional immunity leads to organ-specific inflammatory injuries. Here we
      review the recent developments in the field of tissue-resident immune cells and
      organ-specific regional immunity, and discuss their clinical implication.

PMID- 29170893
TI  - Comparison of the gut microbiota composition between wild and captive sika deer
      (Cervus nippon hortulorum) from feces by high-throughput sequencing.
AB  - The gut microbiota is characterized as a complex ecosystem that has effects on
      health and diseases of host with the interactions of many other factors together.
      Sika deer is the national level for the protection of wild animals in China. The
      available sequencing data of gut microbiota from feces of wild sika deer,
      especially for Cervus nippon hortulorum in Northeast China, are limited. Here, we
      characterized the gastrointestinal bacterial communities of wild (7 samples) and
      captive (12 samples) sika deer from feces, and compared their gut microbiota by
      analyzing the V3-V4 region of 16S rRNA gene using high-throughput sequencing
      technology on the Illumina Hiseq platform. Firmicutes (77.624%), Bacteroidetes
      (18.288%) and Tenericutes (1.342%) were the most predominant phyla in wild sika
      deer. While in captive sika deer, Firmicutes (50.710%) was the dominant phylum,
      followed by Bacteroidetes (31.996%) and Proteobacteria (4.806%). A total of 9
      major phyla, 22 families and 30 genera among gastrointestinal bacterial
      communities showed significant differences between wild and captive sika deer.
      The specific function and mechanism of Tenericutes in wild sika deer need further
      study. Our results indicated that captive sika deer in farm had higher fecal
      bacterial diversity than the wild. Abundance and quantity of diet source for sika
      deer played crucial role in shaping the composition and structure of gut
      microbiota.

PMID- 29170894
TI  - A novel dissociation between representational momentum and representational
      gravity through response modality.
AB  - When people are required to indicate the vanishing location of a moving object,
      systematic biases forward, in the direction of motion, and downward, in the
      direction of gravity, are usually found. Both these displacements, called
      representational momentum and representational gravity, respectively, are thought
      to reflect anticipatory internal mechanisms aiming to overcome neural delays in
      the perception of motion. We challenge this view. There may not be such a single
      mechanism. Although both representational momentum and representational gravity
      follow a specific time-course, compatible with an anticipation of the object's
      dynamics, they do not seem to be commensurable with each other, as they are
      differentially modulated by relevant variables, such as eye movements and
      strength of motion signals. We found separate response components, one related to
      overt motor localization behaviour and one limited to purely perceptual
      judgement. Representational momentum emerged only for the motor localization
      task, revealing a motor overshoot. In contrast, representational gravity was
      mostly evident for spatial perceptual judgements. We interpret the results in
      support of a partial dissociation in the mechanisms that give rise to
      representational momentum and representational gravity, with the former but not
      the latter strongly modulated by the enrolment of the motor system.

PMID- 29170895
TI  - Toward a Psychology of Resistance.
AB  - Resistance is all around us in contemporary life. It is an everyday phenomenon of
      personal and cultural life, as the Chaudhary et al. (2017) volume establishes
      with theoretical analyses and empirical examples from diverse cultural contexts.
      Resistance functions in the dynamics of person-by-culture encounters when one
      party takes an opposing position. With the purpose of working towards a unified
      approach to resistance, the authors in this volume lay down the foundations for a
      psychology of resistance as an everyday phenomenon. As a basis for analyzing the
      role of resistance in the dialectical processes of change, the volume presents
      resistance as: personal and social, oppositional, intentional and future
      oriented, transformational and developmental. We see different positions opening
      up a debate about whether resistance is a particular, intentional and
      oppositional phenomenon, or is the basic process of all dialectical
      transformational change. Further resistance to either position is consistent with
      moving forward in the development of a psychology of resistance.

PMID- 29170896
TI  - Modern Treatments of Haemophilia: Review of Cost-Effectiveness Analyses and
      Future Directions.
AB  - BACKGROUND: Cost is currently one of the most important aspects in haemophilia
      care. Factor concentrates absorb more than 90% of healthcare direct costs of
      haemophilia care, and the debate regarding the high cost of haemophilia
      treatments and their different use across different countries is increasing.
      OBJECTIVE: The objective of this study was to review cost-effectiveness analyses
      conducted on treatment options in haemophilia, focusing on their results and
      their strengths and limitations; to highlight the possible issues associated with
      economic evaluations of new treatment options. METHODS: Electronic searches in
      PubMed and EMBASE were performed to retrieve papers published between November
      2015 and September 2017 to update the previous review of economic evaluations of
      haemophilia treatments by Drummond et al. Reference lists of included articles
      and reviews were examined for relevant studies, which were assessed for their
      quality and their empirical results. RESULTS: Twenty-six relevant economic
      analyses were identified; 15 (57.7%) were conducted in patients with haemophilia
      with inhibitors while 11 (42.3%) involved patients without inhibitors. There were
      methodological variations among the included studies, and differences in the
      treatment schemes make a comparative assessment of interventions for patients
      with haemophilia difficult. Only immune tolerance induction showed consistent
      results in its cost-saving profile compared with the treatment with bypassing
      agents. CONCLUSIONS: Economic evaluations of haemophilia treatments are
      increasing, but the identification of general cost-effectiveness trends is still
      difficult in these studies. We are now facing a new era in haemophilia management
      with a soaring need for high-quality economic evaluations, performed through
      proactive collaboration between clinical experts, budget holders and health
      economists.

PMID- 29170897
TI  - Selective tuning of activity in a multifunctional enzyme as revealed in the F21W
      mutant of dehaloperoxidase B from Amphitrite ornata.
AB  - Possessing both peroxidase and peroxygenase activities with a broad substrate
      profile that includes phenols, indoles, and pyrroles, the enzyme dehaloperoxidase
      (DHP) from Amphitrite ornata is a multifunctional catalytic hemoglobin that
      challenges many of the assumptions behind the well-established structure-function
      paradigm in hemoproteins. While previous studies have demonstrated that the F21W
      variant leads to attenuated peroxidase activity in DHP, here we have studied the
      impact of this mutation on peroxygenase activity to determine if it is possible
      to selectively tune DHP to favor one function over another. Biochemical assays
      with DHP B (F21W) revealed minimal decreases in peroxygenase activity of 1.2-2.1
      fold as measured by 4-nitrophenol or 5-Br-indole substrate conversion, whereas
      the peroxidase activity catalytic efficiency for 2,4,6-trichlorophenol (TCP) was
      more than sevenfold decreased. Binding studies showed a 20-fold weaker affinity
      for 5-bromoindole (K d = 2960 +/- 940 MUM) in DHP B (F21W) compared to WT DHP B.
      Stopped-flow UV/visible studies and isotope labeling experiments together suggest
      that the F21W mutation neither significantly changes the nature of the catalytic
      intermediates, nor alters the mechanisms that have been established for
      peroxidase and peroxygenase activities in DHP. The X-ray crystal structure (1.96
      A; PDB 5VLX) of DHP B (F21W) revealed that the tryptophan blocks one of the two
      identified TCP binding sites, specifically TCPinterior, suggesting that the other
      site, TCPexterior, remains viable for binding peroxygenase substrates. Taken
      together, these studies demonstrate that blocking the TCPinterior binding site in
      DHP selectively favors peroxygenase activity at the expense of its peroxidase
      activity.

PMID- 29170899
TI  - Preoperative urine culture is unnecessary in asymptomatic men prior to prostate
      needle biopsy.
AB  - PURPOSE: To determine the clinical utility of preoperative urine cultures in
      asymptomatic men undergoing prostate needle biopsy (PNB). METHODS: One hundred
      fifty asymptomatic men had urine cultures obtained 14-days prior to PNB. As per
      study protocol, positive cultures were not treated. Antibiotic prophylaxis prior
      to PNB included ciprofloxacin 500 mg the night before and morning of the biopsy.
      Repeat urine cultures were obtained immediately prior to PNB with colony-forming
      units (CFUs) annotated. Infectious complications post-biopsy were recorded.
      RESULTS: Of the 150 men, six patients (4%) had evidence of asymptomatic
      bacteriuria with > 10,000 CFU/mL on office urine culture. Repeat urine cultures
      on morning of biopsy in all 150 patients noted a mean bacterial count of 55
      CFU/mL (range 0-1000). All six patients with positive office urine cultures had <
      100 CFU/mL at time of PNB. Following biopsy, four patients (2.7%) developed an
      infectious complication including two with sepsis and two with culture-positive
      UTIs. The causative organism in all cases was quinolone-resistant E. coli. None
      of the six patients with preoperative positive urine cultures developed an
      infectious complication following PNB. CONCLUSIONS: In this prospective
      observational study, under 5% of asymptomatic men had positive office cultures
      prior to PNB. Furthermore, repeat urine culture on the morning of biopsy showed
      resolution in these patients, and none developed post-biopsy infectious
      complications. Routine office urine culture in the asymptomatic male prior to PNB
      was unnecessary.

PMID- 29170898
TI  - Reconsideration of frailty in relation to surgical indication.
AB  - Given that an increasing number of elderly patients are undergoing surgical
      procedures for a diversity of indications, the concept of frailty is currently
      being examined in more depth in clinical medicine. Established surgical risk
      scores designed to predict mortality are mainly focused on general demographic
      information and clinical factors; however, these do not account for the frailty
      condition. With vulnerability and low resiliency in the frail elderly, these
      conventional scores are unable to accurately predict postoperative outcomes
      including adverse complications, disability, the need for additional
      rehabilitation, and prolonged length of hospitalization. Over the last decade, it
      has been demonstrated that frailty is an independent risk factor of surgery and
      strongly associated with adverse postoperative outcomes and mortality. It is
      essential today that surgeons assimilate the concept of frailty and the
      relationship between frailty and surgical outcomes. A preoperative frailty
      assessment can assist in determining surgical indication and optimal
      perioperative management, ultimately impacting the postoperative functional state
      and quality of life. Here we review the validity of preoperative frailty
      assessments for surgical intervention, possible treatments for frailty, and
      indicate future directions in this field.

PMID- 29170900
TI  - The challenges of closing an ileostomy in patients with total intestinal
      aganglionosis after small bowel transplant.
AB  - We present the case of a 14-year-old male with a history of small bowel
      transplantation for long segment Hirschsprung's disease who underwent Duhamel
      ileorectal pull-through procedure. In post-transplant, the patient had no
      restrictions and was not TPN-dependent. To improve his quality of life, he and
      his family were interested in closing the ileostomy and undergoing pull-through
      surgery. The complexity of the case includes the presence of an aganglionic
      rectal segment-a short root of the mesentery due to the small bowel transplant
      and significant immunosuppression. At the moment, he is continent, doing well,
      and has not had any remarkable complications.

PMID- 29170901
TI  - Randomized, blinded, controlled trial on effectiveness of photobiomodulation
      therapy and exercise training in the fibromyalgia treatment.
AB  - This study evaluated the role of the phototherapy and exercise training (EXT) as
      well as the combined treatment in general symptoms, pain, and quality of life in
      women suffering from fibromyalgia (FM). A total of 160 women were enrolled and
      measures were carried out in two sets: it was sought to identify the acute effect
      for a single phototherapy and EXT session (Set 1); long-term effect (10 weeks) of
      the interventions (Set 2). Phototherapy irradiation was performed at 11 locations
      in their bodies, employing a cluster with nine diodes (one super-pulsed infrared
      905 nm, four light-emitting diodes [LEDs] of 640 nm, and four LEDs of 875 nm,
      39.3 J per location). Algometry and VAS instrument were applied to evaluate pain.
      The FM symptoms were evaluated with Fibromyalgia Impact Questionnaire (FIQ) and
      Research Diagnostic Criteria (RDC) instruments. Quality of life was assessed
      through SF-36 survey. Set 1: pain threshold was improved with the phototherapy,
      and EXT improved the pain threshold for temporomandibular joint (right and left
      body side) and occipital site (right body side). Set 2: there was improved pain
      threshold in several tender points with the phototherapy and EXT. There was an
      overlap of therapies to reduce the tender point numbers, anxiety, depression,
      fatigue, sleep, and difficulty sleeping on FIQ/RDC scores. Moreover, quality of
      life was improved with both therapies. The phototherapy and EXT improved the pain
      threshold in FM women. A more substantial effect was noticed for the combined
      therapy, in which pain relief was accomplished by improving VAS and FIQ scores as
      well as quality of life.

PMID- 29170902
TI  - Carbapenem-heteroresistance among isolates of the Enterobacter cloacae complex:
      is it a real concern?

PMID- 29170903
TI  - "Where Does it Come from?" Experiences Among Survivors and Parents of Children
      with Retinoblastoma in Kenya.
AB  - Genetic testing and counseling have become integral to the timely control of
      heritable cancers, like the childhood eye cancer retinoblastoma. This study aimed
      to determine attitudes, knowledge and experiences related to retinoblastoma
      genetics, among survivors and parents of children with retinoblastoma in Kenya.
      This qualitative study used focus groups as the primary data collection method,
      coupled with a brief demographic questionnaire. Study settings were Kenyatta
      National Hospital and Presbyterian Church of East Africa Kikuyu Hospital.
      Thematic analysis was used to identify key themes. Thirty-one individuals
      participated in five focus groups. Two main concepts emerged: (1) the origins of
      retinoblastoma are unclear, and (2) retinoblastoma is associated with significant
      challenges. The lack of clarity surrounding the origins of retinoblastoma was
      linked to limited knowledge of retinoblastoma genetics, and limited genetic
      counseling delivery and uptake. The challenges associated with retinoblastoma
      were discussed in terms of the impact of the diagnosis on individuals and
      families, and unmet healthcare needs related to the diagnosis. Next steps will
      incorporate these findings to develop evidence-informed and accessible cancer
      genetic services in Kenya.

PMID- 29170904
TI  - Effects of chronic endurance exercise training on serum 25(OH)D concentrations in
      elderly Japanese men.
AB  - BACKGROUND: Higher levels of physical activity and cardiorespiratory fitness are
      positively related to serum 25-hydroxyvitamin D [25(OH)D] concentrations;
      however, the response of 25(OH)D concentrations to chronic endurance exercise
      training is unclear. Therefore, the purpose of this study was to elucidate
      whether serum 25(OH)D concentrations were directly increased by 5 weeks of
      endurance exercise training and influenced by changes in body fat in elderly men.
      METHODS: Twenty elderly Japanese men were randomized to either the 5-week
      endurance exercise training group (ET group; N = 10) or the sedentary control
      group (SC group; N = 10). Fasting blood samples were collected to determine serum
      25(OH)D and other blood parameters. The visceral fat area and hepatic fat content
      were assessed by magnetic resonance imaging and proton magnetic resonance
      spectroscopy, respectively. RESULTS: After 5 weeks of endurance exercise
      training, the levels of maximal oxygen uptake (VO2 max) were significantly
      increased from 23.3 at baseline to 28.1 mL/kg/min at the endpoint for the ET
      group; levels were unchanged for the SC group. A significant seasonal reduction
      in serum 25(OH)D concentrations was observed in the SC group (P < 0.05), while no
      change was found in the ET group. The results may be partly attributed to the
      slight decrease in intrahepatic fat in the ET group. No changes were observed in
      percent body fat or visceral fat area. CONCLUSIONS: The results of our study
      suggest that 5 weeks of endurance training could inhibit the seasonal reduction
      in serum 25(OH)D concentrations without changes in body fat.

PMID- 29170906
TI  - Bevacizumab and risk of intracranial hemorrhage in patients with brain
      metastases: a meta-analysis.
AB  - Administration of bevacizumab to patients with brain metastases (BM) is
      controversial due to concerns about the increased risk of intracranial hemorrhage
      (ICH). This meta-analysis assessed whether the risk of ICH increases in BM
      patients receiving treatments that contain bevacizumab versus without. PubMed,
      Embase, Cochrane Library and annual meeting abstracts of the American Society of
      Clinical Oncology up to 13 November 2016 were searched for studies that referred
      to ICH complications due to bevacizumab in patients with BM. Eight studies
      involving 8713 patients were included in this analysis. Compared with the control
      arm without bevacizumab, the bevacizumab treatment arm did not exhibit a
      significant increase in ICH [odds ratio (OR) 1.20; 95% confidence intervals (CI)
      0.69-2.09; P = 0.53]. Subgroup analyses with retrospective studies showed a
      similar result, although subgroup analyses with prospective studies failed. This
      meta-analysis revealed that bevacizumab does not significantly increase the risk
      of ICH in solid tumor patients with BM.

PMID- 29170905
TI  - Irisin in metabolic diseases.
AB  - INTRODUCTION: Irisin is a myokine/adipokine induced by the exercise in mice and
      humans, which is proposed to induce "browning" of white adipose tissue, its
      primary target, thus increasing thermogenesis and energy expenditure. Since its
      identification, irisin has been linked to favorable effects on metabolic
      diseases, including obesity, type 2 diabetes mellitus (T2DM), lipid metabolism
      and cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD),
      polycystic ovary syndrome (PCOS), and metabolic bone diseases. Generally, despite
      the promising profile of irisin in rodents, its effects on human are less
      recognized. REVIEW: Most, but not all studies show a positive association between
      irisin and indices of adiposity. In T2DM, NAFLD, and CVD, most observational
      studies reported lower irisin levels in patients than controls. Regarding
      metabolic bone diseases, irisin is positively associated with bone mineral
      density and strength in athletes, and inversely associated with osteoporotic
      fractures in postmenopausal osteoporosis. In PCOS, data remain largely
      conflicting. Irisin does not seem to be further reduced when two metabolic
      diseases, e.g., T2DM and NAFLD, or obesity and NAFLD exist though more data are
      needed. Furthermore, it seems that diverse confounders may have affected the
      results of different clinical studies. CONCLUSION: Irisin remains an appealing
      molecule from a pathophysiological point of view and an appealing therapeutic
      target for metabolic diseases, albeit much research is still needed.

PMID- 29170907
TI  - An immune-related lncRNA signature for patients with anaplastic gliomas.
AB  - We investigated immune-related long non-coding RNAs (lncRNAs) that may be
      exploited as potential therapeutic targets in anaplastic gliomas. We obtained 572
      lncRNAs and 317 immune genes from the Chinese Glioma Genome Atlas microarray and
      constructed immune-related lncRNAs co-expression networks to identify immune
      related lncRNAs. Two additional datasets (GSE16011, REMBRANDT) were used for
      validation. Gene set enrichment analysis and principal component analysis were
      used for functional annotation. Immune-lncRNAs co-expression networks were
      constructed. Nine immune-related lncRNAs (SNHG8, PGM5-AS1, ST20-AS1, LINC00937,
      AGAP2-AS1, MIR155HG, TUG1, MAPKAPK5-AS1, and HCG18) signature was identified in
      patients with anaplastic gliomas. Patients in the low-risk group showed longer
      overall survival (OS) and progression-free survival than those in the high-risk
      group (P < 0.0001; P < 0.0001). Additionally, patients in the high-risk group
      displayed no-deletion of chromosomal arms 1p and/or 19q, isocitrate dehydrogenase
      wild-type, classical and mesenchymal TCGA subtype, G3 CGGA subtype, and lower
      Karnofsky performance score (KPS). Moreover, the signature was an independent
      factor and was significantly associated with the OS (P = 0.000, hazard ratio (HR)
      = 1.434). These findings were further validated in two additional datasets
      (GSE16011, REMBRANDT). Low-risk and high-risk groups displayed different immune
      status based on principal components analysis. Our results showed that the nine
      immune-related lncRNAs signature has prognostic value for anaplastic gliomas.

PMID- 29170908
TI  - Local control and overall survival for adjuvant stereotactic radiosurgery in
      patients with residual or recurrent disease.
AB  - Prior studies of post-operative stereotactic radiosurgery (SRS) have not
      distinguished between Adjuvant SRS (ARS) versus Adjuvant SRS to
      residual/recurrent disease (ARD). In this study, we defined ARS and ARD and
      investigated local control (LC), overall survival (OS), distant development of
      brain metastases (DBF), and leptomeningeal disease (LMD). We retrospectively
      identified BM patients who received surgical resection and SRS for BM from an IRB
      approved database between Jan 2009-Aug 2015. Patients were stratified into two
      groups: ARS and ARD. LC was determined by follow-up MRI studies and OS was
      measured from the date of surgery. LC and OS were assessed using the Kaplan-Meier
      method. 70 cavities underwent surgical resection of BM and received SRS to the
      post-operative bed. 41 cavities were classified as ARS and 29 as ARD. There was
      no significant difference in 12-month LC between the ARS and ARD group (71.4 vs.
      80.8%, respectively; p = 0.135) from the time point of SRS. The overall 1-year
      survival for ARS and ARD was 79.9 and 86.1%, respectively (p = 0.339). Mean time
      to progression was 6.45 and 8.0 months and median follow-up was 10 and 15 months
      for ARS and ARD, respectively. 11.8% of ARS patients and 15.4% of ARD patients
      developed LMD, p = 0.72. 29.4% of ARS and 48.0% of ARD patients developed DBF, p
      = 0.145. Our findings suggest that observation after surgical resection, with
      subsequent treatment with SRS after the development of local failure, may not
      compromise treatment efficacy. If validated, this would spare patients who do not
      recur post-surgically from additional treatment.

PMID- 29170909
TI  - New therapeutic approaches for brainstem tumors: a comparison of delivery routes
      using nanoliposomal irinotecan in an animal model.
AB  - Despite the advances in imaging, surgery and radiotherapy, the majority of
      patients with brainstem gliomas die within 2 years after initial diagnosis.
      Factors that contribute to the dismal prognosis of these patients include the
      infiltrative nature and anatomic location in an eloquent area of the brain, which
      prevents total surgical resection and the presence of the blood-brain barrier
      (BBB), which reduces the distribution of systemically administered agents. The
      development of new therapeutic approaches which can circumvent the BBB is a
      potential path to improve outcomes for these children. Convection-enhanced
      delivery (CED) and intranasal delivery (IND) are strategies that permit direct
      drug delivery into the central nervous system and are an alternative to
      intravenous injection (IV). We treated rats bearing human brainstem tumor
      xenografts with nanoliposomal irinotecan (CPT-11) using CED, IND, and IV. A
      single treatment of CED irinotecan had a similar effect on overall survival as
      multiple treatments by IV route. IND CPT-11 showed significantly increased
      survival of animals with brainstem tumors, and demonstrated the promise of this
      non-invasive approach of drug delivery bypassing the BBB when combined with
      nanoliposomal chemotherapy. Our results indicated that using CED and IND of
      nanoliposomal therapy increase likelihood of practical therapeutic approach for
      the treatment of brainstem gliomas.

PMID- 29170910
TI  - Bioenergetic reprogramming plasticity under nitrogen depletion by the unicellular
      green alga Scenedesmus obliquus.
AB  - MAIN CONCLUSION: Simultaneous nitrogen depletion and 3,4-dichlorophenol addition
      induce a bioenergetic microalgal reprogramming, through strong Cyt b 6 f
      synthesis, that quench excess electrons from dichlorophenol's biodegradation to
      an overactivated photosynthetic electron flow and H 2 -productivity. Cellular
      energy management includes "rational" planning and operation of energy production
      and energy consumption units. Microalgae seem to have the ability to calculate
      their energy reserves and select the most profitable bioenergetic pathways. Under
      oxygenic mixotrophic conditions, microalgae invest the exogenously supplied
      carbon source (glucose) to biomass increase. If 3,4-dichlorophenol is added in
      the culture medium, then glucose is invested more to biodegradation rather than
      to growth. The biodegradation yield is enhanced in nitrogen-depleted conditions,
      because of an increase in the starch accumulation and a delay in the
      establishment of oxygen-depleted conditions in a closed system. In nitrogen
      depleted conditions, starch cannot be invested in PSII-dependent and PSII
      independent pathways for H2-production, mainly because of a strong decrease of
      the cytochrome b 6 f complex of the photosynthetic electron flow. For this
      reason, it seems more profitable for the microalga under these conditions to
      direct the metabolism to the synthesis of lipids as cellular energy reserves.
      Nitrogen-depleted conditions with exogenously supplied 3,4-dichlorophenol induce
      reprogramming of the microalgal bioenergetic strategy. Cytochrome b 6 f is
      strongly synthesized (mainly through catabolism of polyamines) to manage the
      electron bypass from the dichlorophenol biodegradation procedure to the
      photosynthetic electron flow (at the level of PQ pool) and consequently through
      cytochrome b 6 f and PSI to hydrogenase and H2-production. All the above showed
      that the selection of the appropriate cultivation conditions is the key for the
      manipulation of microalgal bioenergetic strategy that leads to different
      metabolic products and paves the way for a future microalgal "smart"
      biotechnology.

PMID- 29170911
TI  - Characterization of an acetohydroxy acid synthase mutant conferring tolerance to
      imidazolinone herbicides in rice (Oryza sativa).
AB  - MAIN CONCLUSION: The acetohydroxy acid synthase S627N mutation confers herbicide
      tolerance in rice, and the rice variety containing this mutation produces good
      yields. This variety is commercially viable at Shanghai and Jiangsu regions in
      China. Weedy rice is a type of rice that produces lower yields and poorer quality
      grains than cultivated rice. It plagues commercial rice fields in many countries.
      One strategy to control its proliferation is to develop rice varieties that are
      tolerant to specific herbicides. Acetohydroxy acid synthase (AHAS) mutations have
      been found to confer herbicide tolerance to rice. Here, we identified a single
      mutation (S627N) in AHAS from an indica rice variety that conferred tolerance
      against imidazolinone herbicides, including imazethapyr and imazamox. A japonica
      rice variety (JD164) was developed to obtain herbicide tolerance by introducing
      the mutated indica ahas gene. Imidazolinone application was sufficient to
      efficiently control weedy rice in the JD164 field. Although the imazethapyr
      treatment caused dwarfing in the JD164 plants, it did not significantly reduce
      yields. To determine whether the decrease of the ahas mRNA expression caused the
      dwarfism of JD164 after imazethapyr application, we detected the ahas mRNA level
      in plants. The abundance of the ahas mRNA in JD164 increased after imidazolinone
      application, thus excluding the mRNA expression level as a possible cause of
      dwarfism. Activity assays showed that the mutated AHAS was tolerant to
      imidazolinone but the catalytic efficiency of the mutated AHAS decreased in its
      presence. Moreover, the activity of the mutated AHAS decreased more in the
      presence of imazethapyr than in the presence of imazamox. We observed no
      difference in the AHAS secondary structures, but homology modeling suggested that
      the S627N mutation enabled the substrate to access the active site channel in
      AHAS, resulting in imidazolinone tolerance. Our work combined herbicides with a
      rice variety to control weedy rice and showed the mechanism of herbicide
      tolerance in this rice variety.

PMID- 29170912
TI  - Relationships between water status and photosystem functionality in a
      chlorolichen and its isolated photobiont.
AB  - MAIN CONCLUSION: Drought tolerance was greater in the whole lichen than in its
      isolated photobiont. Cell turgor state has an influence on the functionality of
      photosynthetic process in lichens. Irreversible thermodynamics is widely used to
      describe the water relations of vascular plants. However, poikilohydrous
      organisms like lichens and aeroterrestrial microalgae have seldom been studied
      using this approach. Water relations of lichens are generally addressed without
      separate analysis of the mycobiont and photobiont, and only few studies have
      correlated changes in photosynthetic efficiency of dehydrating lichens to
      accurate measurements of their water potential components. We measured water
      potential isotherms and chlorophyll a fluorescence in the lichen Flavoparmelia
      caperata harvested in different seasons, as well as in its isolated photobiont,
      the green alga Trebouxia gelatinosa, either exposed to water stress cycles or
      fully hydrated. No significant seasonal trends were observed in lichen water
      relations parameters. Turgor loss point and osmotic potential of the whole
      thallus were significantly lower than those measured in the photobiont, while
      differences between the water stressed photobiont and controls were not
      significant. Dehydration-induced drop of F v/F m was correlated with turgor loss,
      revealing that the photosynthetic activity of lichens partly depends on their
      turgor level. We provided one of the first quantitative evidences of the
      influence that turgor status could exert on the functionality of photosynthetic
      processes in lichens.

PMID- 29170913
TI  - Impact of HBV replication in peripheral blood mononuclear cell on HBV
      intrauterine transmission.
AB  - This study determined the effect of hepatitis B virus (HBV) replication in
      peripheral blood mononuclear cell (PBMC) from HBsAg-positive mothers on HBV
      intrauterine transmission. A total of 150 HBsAg-positive mothers and their
      neonates were recruited in this study. Within 24 h after birth, HBV serological
      markers, serum HBV DNA, PBMC HBV relaxed circular DNA (rcDNA), and covalently
      closed circular DNA (cccDNA) were measured in the HBsAg-positive mothers and
      their neonates before passive-active immune prophylaxis. The relationship between
      HBV replication in PBMC and HBV intrauterine transmission was examined through
      Chisquare test and logistic regression. The rate of HBV intrauterine transmission
      was 8.00% (12/150) in the 150 neonates born to HBsAg-positive mothers. The
      positivities of PBMC HBV rcDNA and cccDNA in the HBsAg-positive mothers were
      36.67% (55/150) and 10% (15/150), respectively. Maternal PBMC HBV cccDNA was a
      risk factor of HBV intrauterine transmission (OR = 6.003, 95% CI: 1.249-28.855).
      Maternal serum HBeAg was a risk factor of PBMC HBV rcDNA (OR = 3.896, 95% CI:
      1.929-7.876) and PBMC HBV cccDNA (OR = 3.74, 95% CI: 1.186-11.793) in the HBsAg
      positive mothers. Administration of hepatitis B immune globulin was a protective
      factor of PBMC HBV cccDNA (OR = 0.312, 95%CI: 0.102-0.954) during pregnancy. The
      positivity of PBMC HBV rcDNA was related to that of cccDNA in the HBsAg-positive
      mothers (chi 2= 5.087, P = 0.024). This study suggests that PBMC is a reservoir
      of HBV and an extrahepatic site for virus replication and plays a critical role
      in HBV intrauterine transmission.

PMID- 29170914
TI  - Immunological and virological characteristics of human immunodeficiency virus
      type 1 superinfection: implications in vaccine design.
AB  - Superinfection is frequently detected among individuals infected by human
      immunodeficiency virus type I (HIV-1). Superinfection occurs at similar
      frequencies at acute and chronic infection stages but less frequently than
      primary infection. This observation indicates that the immune responses elicited
      by natural HIV-1 infection may play a role in curb of superinfection; however,
      these responses are not sufficiently strong to completely prevent superinfection.
      Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader
      immune responses than those elicited by primary infection. On the other hand,
      potent and broad neutralization responses are more often detected after
      superinfection than during monoinfection. This suggests that broadly neutralizing
      antibodies are more likely induced by sequential immunization of multiple
      different immunogens than with only one form of envelope glycoprotein immunogens.
      Understanding why the protection from superinfection by immunity induced by
      primary infection is insufficient and if superinfection can lead to cross
      reactive immune responses will be highly informative for HIV-1 vaccine design.

PMID- 29170915
TI  - Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in
      the era of nucleos(t)ide analogs.
AB  - Although the efficacy of nucleos(t)ide analogue (NA) has been confirmed for
      treatment of chronic hepatitis B, long-term therapy has been recommended due to
      the high frequency of off-therapy viral DNA rebound and disease relapse. In this
      review, the RNA virion-like particles of hepatitis B virus (HBV) are integrated
      into the life cycle of HBV replication, and the potential significance of serum
      HBV RNA is systematically described. The production of HBV RNA virion-like
      particles should not be blocked by NA; in this regard, serum HBV RNA is found to
      be a suitable surrogate marker for the activity of intrahepatic covalently closed
      circular DNA (cccDNA), particularly among patients receiving NA therapy.
      Therefore, the concept of virological response is redefined as persistent loss of
      serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen (HBsAg)
      that can originate from either the cccDNA or the integrated HBV DNA fragment,
      serum HBV RNA, with pregenomic RNA origination, can only be transcribed from
      cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising
      predicator for safe drug discontinuation. The clinical status of consistent loss
      of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a
      "para-functional cure," a status nearly close to the functional cure of chronic
      hepatitis B, to distinguish the "functional cure" characterized as serum HBsAg
      loss with or without anti-HBs seroconversion.

PMID- 29170916
TI  - Development of small-molecule viral inhibitors targeting various stages of the
      life cycle of emerging and re-emerging viruses.
AB  - In recent years, unexpected outbreaks of infectious diseases caused by emerging
      and re-emerging viruses have become more frequent, which is possibly due to
      environmental changes. These outbreaks result in the loss of life and economic
      hardship. Vaccines and therapeutics should be developed for the prevention and
      treatment of infectious diseases. In this review, we summarize and discuss the
      latest progress in the development of small-molecule viral inhibitors against
      highly pathogenic coronaviruses, including severe acute respiratory syndrome
      coronavirus and Middle East respiratory syndrome coronavirus, Ebola virus, and
      Zika virus. These viruses can interfere with the specific steps of viral life
      cycle by blocking the binding between virus and host cells, disrupting viral
      endocytosis, disturbing membrane fusion, and interrupting viral RNA replication
      and translation, thereby demonstrating potent therapeutic effect against various
      emerging and re-emerging viruses. We also discuss some general strategies for
      developing small-molecule viral inhibitors.

PMID- 29170917
TI  - Radical versus conservative surgical treatment of liver hydatid cysts: a meta
      analysis.
AB  - To date, the efficacy of radical surgery (RS) versus conservative surgery (CS)
      for liver hydatid cysts (LHC) remains controversial. This meta-analysis was
      conducted to compare the two interventions. PubMed, Embase, and Web of Science
      were searched from their inceptions until June 2016. Meta-analysis was performed
      using STATA 12.0 software. We identified 19 eligible studies from 10 countries by
      retrieval. In total, 1853 LHC patients who received RS were compared with 2274
      patients treated by CS. The risk of postoperative overall complication, biliary
      fistula, and recurrence was significantly lower, and operation time was
      significantly longer in the RS group. However, no statistically significant
      differences were found in terms of mortality risk and the duration of hospital
      stay between RS and CS. No significant publication biases were observed in all
      the above analyses. In conclusion, RS reduces the rates of postoperative
      complications and recurrence, whereas no trend toward such a reduction in
      mortality was observed in LHC patients.

PMID- 29170918
TI  - Determining "abnormal" levator hiatus distensibility using three-dimensional
      transperineal ultrasound in Chinese women.
AB  - The dimension of the levator hiatus is a possible predictor of pelvic organ
      prolapse (POP). This retrospective study investigated 360 women who went to
      urogynecological clinic for pelvic floor discomfort. Levator hiatus dimensions
      were obtained by three-dimensional transperineal ultrasound and results were
      compared between women with and without significantly objective prolapse
      (International Continence Society POP quantification, grade 2 or higher).
      Receiver operating characteristic (ROC) curve analyses were performed to
      determine valid screening index for detecting abnormal levator hiatus
      distensibility. Women with significantly objective prolapse had significantly
      higher levator hiatus dimensions than those without (all P < 0.001). ROC curve
      analyses confirmed that hiatal area (HA) of 19.5 cm2 during Valsalva maneuver can
      be used as single-screening index for abnormal levator hiatus distensibility with
      sensitivity of 0.80 and specificity of 0.70. In this study, we used a two-step
      method and achieved higher sensibility (0.80 vs. 0.87) without reducing
      specificity (0.70 vs. 0.71) compared with a single-screening index method. As a
      result, we suggest that HA ? 19.5 cm2 during Valsalva maneuver is an indicator of
      abnormal levator hiatus distensibility in Chinese women and that the two-step
      method has higher sensitivity in detecting abnormal distensibility.

PMID- 29170920
TI  - Dacrystic Epilepsy.

PMID- 29170921
TI  - Unexplained Transaminitis and Hyperactivity: Do Not Forget the Musculoskeletal
      Examination.

PMID- 29170919
TI  - Current advances in the elimination of hepatitis B in China by 2030.
AB  - With its 78 million chronic carriers, hepatitis B virus (HBV) infection is still
      one of the leading public health challenges in China. Over the last two decades,
      China has made great progress on the prevention of HBV transmission through
      national vaccination programs. Zero transmission from mother to infant has been
      proposed as the current goal. Available anti-HBV therapy is efficacious in
      suppressing HBV replication; however, it fails to completely cure patients with
      chronic hepatitis B and even requires lifelong treatment. To reduce the costs and
      improve the efficacy, several trials have been recently conducted in China to
      optimize the current anti-HBV managements. Novel biomarkers were identified to
      predict treatment outcomes, and new promising treatment strategies were
      developed. Reports also indicate that coinfections of HBV with other hepatotropic
      viruses and human immunodeficiency virus are common in China and cause severe
      liver diseases, which should be recognized early and treated properly. Work is
      still needed to eliminate hepatitis B in China by 2030.

PMID- 29170922
TI  - Vaccine Safety and Surveillance for Adverse Events Following Immunization (AEFI)
      in India.
AB  - RATIONALE: Assured quality vaccines and safe immunization practices are pre
      requisite to successful immunization programs. All vaccines go through stringent
      safety checks during pre-licensure stage. Adverse Events Following Immunization
      (AEFI) Surveillance program is an integral part of routine immunization program
      in India to monitor the vaccine safety in the post licensure phase. Indian AEFI
      Program: National AEFI surveillance relies on passive surveillance and reporting
      by the health functionaries and practitioners. Vigorous strengthening of AEFI
      surveillance has resulted in manifold rise in absolute number of AEFI reports
      across several reporting units in the country in the last decade. Establishment
      of National AEFI Secretariat, National Technical Collaborating Centre, and
      development of risk communication strategy as well as quality management
      certification are some of the unique aspects of this public health program. All
      serious AEFI reports undergo a systematic causality assessment as per WHO
      algorithm by trained committees. National AEFI surveillance system has forged
      formal linkages with national pharmacovigilance program, the regulators, and
      professional bodies. Challenges: The number of the reported serious AEFIs are
      still far less than the expected numbers. Although the AEFI committees at the
      district and state levels have been established, a large proportion are far from
      functional. Way forward: As the national immunization program introduces newer
      vaccines for different age groups and coverage improves, the issues of vaccine
      hesitancy and confidence are likely to be raised more often and the AEFI
      surveillance program will have to assume greater responsibility to
      comprehensively respond to the community concerns and sustain public confidence
      in vaccines.

PMID- 29170924
TI  - Frontotemporal Atrophy: Presenting Sign in Infantile Cobalamin Deficiency.

PMID- 29170923
TI  - Urinary Screening for Early Detection of Kidney Diseases.
AB  - OBJECTIVE: Urinary screening is a simple inexpensive tool to evaluate kidney
      functions. The authors carried out urinary screening of school children for early
      detection of kidney diseases. METHODS: Children in the age group 5-15 y were
      screened for urinalysis. They were divided in 2 groups; group-1 included 5-10 y
      and group-2 included >10-15 y old children. RESULTS: Urine samples of 3340(78%)
      out of 4283 enrolled children were tested. Abnormal samples were found in 5.75%;
      with proteinuria in 4.59%, pyuria in 3.29% and hematuria in 4.31%. Males
      constituted 47.71% in group-1 and 54.64% in group-2. Low body mass index was
      found in 94.1% group-1 and 78.99% group-2 children. Mild proteinuria was found in
      1.2% group-1 and 2.56% group-2 children. Severe proteinuria was more in group-2
      (0.77% vs. 0.06%) with female preponderance. Glucosuria was found in 1 boy of
      group-2. Urobilinogen was more in group-2 (0.65% vs. 0.24%) with male
      preponderance. Nitrituria was found in 9 girls. Pyuria (2.02% vs. 1.27%) and
      hematuria were more in group-2 (3.04% vs. 1.87%) with female preponderance.
      Combined proteinuria and hematuria (0.42% vs. 0.24%) as well bacteruria and
      fungaluria were more in group-2 (4.11% vs. 1.39%). Six of 192 children with
      abnormal urinary findings were treated; 1 for urinary calculus and 5 for urinary
      tract infection. CONCLUSIONS: Abnormal urinary findings were more common in
      children >10 y of age. Thus urinary screening program of children can become
      useful for early detection of kidney diseases and contribute towards building up
      of a healthy nation.

PMID- 29170925
TI  - Recycling of wastes from fish beneficiation by composting: chemical
      characteristics of the compost and efficiency of their humic acids in stimulating
      the growth of lettuce.
AB  - Waste from the beneficiation of fish was composted with crushed grass aiming to
      characterize their chemical composition and investigate the possibility of the
      use of the final compost as source of humic acids (HA) able to stimulate the
      growth of lettuce. Compost presented pH value, C/N ratio, and electrical
      conductivity that allow its use as an organic fertilizer. The element content was
      present in the following order of abundance in the compost: P > Ca > N > Mg > K >
      Fe > Zn > Mn > Mo > Cu, and the humus composition was similar to that observed in
      others kind of organic residues composted. The high content of oxygen pointed out
      a high level of oxidation of HA, in line with the predominance of phenolic
      acidity in the functional groups. The 13C-NMR spectra showed marked resonances
      due to the presence of lipids and other materials resistant to degradation as
      methoxy substituent and N-alkyl groups. A concentration of 20 mg L-1 HA increased
      significantly both dry and wet root matter in lettuce but the CO2 assimilation,
      stomatal conductance, and number of lateral roots of the plants were not
      affected. However, increases of 64% in the water-use efficiency was observed due
      to the HA addition, probably related to the root morphology alteration which
      resulted in 1.6-fold increase of lateral root average length and due to the
      higher H+ extrusion activity. Reuse of residues from the fish beneficiation
      activity by composting may represent a safe tool to increase the value of
      recycled organic residues and generate HA with potential use as plant growth
      stimulants.

PMID- 29170927
TI  - Climate mitigation, low-carbon society, and dynamism of educational institutes in
      a low-income country.
AB  - This paper aims to investigate carbon footprints of faculty members of University
      of Agriculture Faisalabad (UAF) associated with income and education in pursuance
      of a low-carbon society. For the study, 140 UAF faculty members (professors,
      associate professors, assistant professors, and lecturers) were selected using
      stratified random sampling technique, and a representative questionnaire was used
      to record primary data. Moreover, the ordinary least square (OLS) method was used
      to explain the statistical relationship between income, education, and carbon
      footprints. It was found that carbon footprints of UAF faculty members were 10.06
      metric tons (mt) per year per person on an average. Our results further indicated
      that carbon footprints of assistant professors, associate professors, and
      professors were 10.83, 11.95, and 10.96 mt per person per annum, respectively.
      OLS estimates showed that an increase in one Doctor of Philosophy (Ph.D.) faculty
      member increases the carbon footprint by 1.15 mt per annum. Male faculty members
      emit more carbon footprints than females. Faculty members of Tenure Track System
      (TTS) had a higher income than those of Basic Pay Scale (BPS). Therefore,
      emissions of TTS faculty members were higher. Hence, in order to reduce carbon
      footprints and corroborate UAF campus environment-friendly, the attitude towards
      this aspect should be changed and awareness should be created. Furthermore,
      reduced car usage can be another bottom-up policy suggestion. As witnessed in
      green campuses of international universities, UAF should also be a motor-free
      campus (cycling and pedestrian only).

PMID- 29170926
TI  - Chemometric and high-resolution mass spectrometry tools for the characterization
      and comparison of raw and treated wastewater samples of a pilot plant on the
      SIPIBEL site.
AB  - Due to its key role in the contamination of natural resources, the assessment of
      raw and treated wastewater effluents is a current major concern and urges
      comprehensive analytical methods capable of selectively capturing the
      chemodiversity of these samples. In this context, the overall objective of this
      work can be summarized as (i) the assessment of the performance of secondary and
      tertiary (advanced oxidation) wastewater treatments through multivariate analysis
      followed by (ii) the comprehensive characterization of wastewater samples based
      on their spectral fingerprints and a combination of suspect and non-target
      screening approaches. Several compounds, belonging to different sources of
      contamination were annotated and/or partially identified: pharmaceuticals,
      metabolites and transformation compounds, human activity markers, surfactants,
      and polyethoxy compounds. These results highlight the contribution of filtering
      and screening tools such as monoisotopic exact mass, mass defect, MS/MS data
      dependent acquisitions, isotopic pattern and retention time to the selection, and
      the identification of environmental contaminants and their
      metabolites/degradation products. This paper completes the target study conducted
      in the SIPIBEL site and offers an alternative for the assessment of treatment
      processes by broadening the spectrum to a larger number of compounds and the
      correlations between them.

PMID- 29170929
TI  - The Validity of Bioelectrical Impedance Analysis to Measure Body Composition in
      Phenylketonuria.
AB  - AIM: To compare the measurement of total body water (TBW) and fat-free mass (FFM)
      using the criterion method of deuterium dilution space (2H2O) with bioelectrical
      impedance analysis (BIA) using a portable QuadScan 4000, Bodystat(r) in children
      and adolescents with phenylketonuria (PKU). METHODS: Sixteen patients with PKU,
      median age is 12.5 (range 5-20.6) years, were recruited into this cross-sectional
      study. TBW was measured by both deuterium dilution and BIA on the same occasion
      as per a standard protocol. FFM was estimated from predictive equations. RESULTS:
      There was no significant difference between TBWDeut and TBWBIA (p = 0.344) or
      FFMDeut and FFMBIA (p = 0.111). TBWDeut and TBWBIA were highly correlated (r =
      0.990, p < 0.0001), as were FFMDeut and FFMBIA (r = 0.984, p < 0.0001). Bland
      Altman plots demonstrated that there was no proportional bias between the
      criterion method, TBWDeut, and the test method TBWBIA, in estimating TBW (beta = 
      0.056, adjusted r 2 = 0.069, p = 0.169) or FFM (beta = -0.089, adjusted r 2 =
      0.142, p = 0.083). CONCLUSION: Our results suggest that when compared with the
      criterion method, the QuadScan 4000, Bodystat(r) can reliably be used to predict
      TBW and FFM in patients with PKU. We suggest that due to the portability and non
      invasive approach, this method can reliably be used to monitor body composition
      in the outpatient clinic setting, to further improve the monitoring and
      assessment of nutritional status in PKU.

PMID- 29170928
TI  - Leishmania mexicana differentiation involves a selective plasma membrane
      autophagic-like process.
AB  - Parasites of the Leishmania genus, which are the causative agents of
      leishmaniasis, display a complex life cycle, from a flagellated form
      (promastigotes) residing in the midgut of the phlebotomine vector to a non
      flagellated form (amastigote) invading the mammalian host. The cellular process
      for the conversion between these forms is an interesting biological phenomenon
      involving modulation of the plasma membrane. In this study, we describe a
      selective autophagic-like process during the in vitro differentiation of
      Leishmania mexicana promastigote to amastigote-like cells. This process is
      responsible for size reduction and shape change of the promastigote (15-20 MUm
      long) to the rounded amastigote-like form (4-5 MUm long), identical to the one
      that infects host macrophages. This autophagic-like process is characterized by a
      profound folding of the plasma membrane and the presence of abundant cytoplasmic
      lipid droplets that may be the product of changes in the lipid metabolism. The
      key feature for the differentiation process at either pH 7.0 or pH 5.5 is the
      shift in temperature from 25 to 35  degrees C. Flagella shortening during the
      differentiation process appears as the product of continuous flagellar
      microtubular disassembly that is also accompanied by changes in mitochondrion
      localization. Drugs directed at blocking the parasite autophagic-like process
      could be important as new strategies to fight the disease.

PMID- 29170930
TI  - Age-Specific Patient Navigation Preferences Among Adolescents and Young Adults
      with Cancer.
AB  - BACKGROUND: Patient navigation is increasingly being directed at adolescent and
      young adult (AYA) patients. This study provides a novel description of
      differences in AYA cancer patients' preferences for navigation services by
      developmental age at diagnosis. METHODS: Eligible patients were diagnosed with
      cancer between ages 15 and 39 and had completed at least 1 month of treatment.
      Between October 2015 and January 2016, patients completed semi-structured
      interviews about navigation preferences. Summary statistics of demographic and
      cancer characteristics were generated. Differences in patient navigation
      preferences were examined through qualitative analyses by developmental age at
      diagnosis. RESULTS: AYAs were interviewed (adolescents 15-18 years N = 8;
      emerging adults 19-25 years N = 8; young adults 26-39 years N = 23). On average,
      participants were 4.5 years from diagnosis. All age groups were interested in
      face-to-face connection with a navigator and using multiple communication
      platforms (phone, text, email) to follow-up. Three of the most frequently cited
      needs were insurance, finances, and information. AYAs differed in support,
      healthcare, and resource preferences by developmental age; only adolescents
      preferred educational support. While all groups preferred financial and family
      support, the specific type of assistance (medical versus living expenses,
      partner/spouse, child, or parental assistance) varied by age group. CONCLUSIONS:
      AYAs with cancer have different preferences for patient navigation by
      developmental age at diagnosis. AYAs are not a one-size-fits-all population, and
      navigation programs can better assist AYAs when services are targeted to
      appropriate developmental ages. Future research should examine fertility and
      navigation preferences by time since diagnosis. While some navigation needs to
      span the AYA age range, other needs are specific to developmental age.

PMID- 29170931
TI  - Fate, toxicity and bioconcentration of cadmium on Pseudokirchneriella subcapitata
      and Lemna minor in mid-term single tests.
AB  - In the frame of a project which consists in modeling a laboratory microcosm under
      cadmium pressure, we initiated this study on the fate and effects of cadmium in
      the presence of either the microalga Pseudokirchneriella subcapitata or the
      duckweed Lemna minor, two organisms of the microcosm. For each organism, growth
      inhibition tests on a duration of 2-3 weeks were carried out with the objective
      of linking effects with total dissolved, ionic and internalized forms of cadmium.
      Numbers of organisms (algal cells or duckweed fronds) in 2-L beakers filled with
      synthetic nutritive medium containing EDTA were counted during the course of
      assays, while cadmium concentrations in the water and in the organisms were
      measured. Free cadmium fraction was calculated using PHREEQC, a computer program
      for chemical speciation. Results showed that cadmium toxicity to microalgae could
      be correlated to the free divalent fraction of this metal, limited by the
      presence of EDTA, and to its concentration in the organisms. Bioconcentration
      factors for our medium were suggested for P. subcapitata (111,000 on the basis of
      free cadmium concentration) and L. minor (17,812 on the basis of total dissolved
      concentration). No effect concentrations were roughly estimated around 400 ug/g
      for Pseudokirchneriella subcapitata and 200-300 ug/g for Lemna minor. This study
      is a first step towards a fate model based on chemical speciation for a better
      understanding of microcosm results.

PMID- 29170932
TI  - Estimating cross quantile residual ratio with left-truncated semi-competing risks
      data.
AB  - A semi-competing risks setting often arises in biomedical studies, involving both
      a nonterminal event and a terminal event. Cross quantile residual ratio (Yang and
      Peng in Biometrics 72:770-779, 2016) offers a flexible and robust perspective to
      study the dependency between the nonterminal and the terminal events which can
      shed useful scientific insight. In this paper, we propose a new nonparametric
      estimator of this dependence measure with left truncated semi-competing risks
      data. The new estimator overcomes the limitation of the existing estimator that
      is resulted from demanding a strong assumption on the truncation mechanism. We
      establish the asymptotic properties of the proposed estimator and develop
      inference procedures accordingly. Simulation studies suggest good finite-sample
      performance of the proposed method. Our proposal is illustrated via an
      application to Denmark diabetes registry data.

PMID- 29170933
TI  - Impact of previous episodes of hepatic encephalopathy on short-term brain
      function recovery after liver transplantation: a functional connectivity strength
      study.
AB  - Neuropsychological studies have documented an incomplete reversal of pre-existing
      cognitive dysfunction in cirrhotic patients after liver transplantation (LT) and
      have found this is more severe in patients with hepatic encephalopathy (HE). In
      this study, we aimed to investigate the impact of prior HE episodes on post
      transplantation brain function recovery. Resting-state functional magnetic
      resonance imaging data was collected from 30 healthy controls and 33 cirrhotic
      patients (HE, n = 15 and noHE, n = 18) before and one month after LT. Long- and
      short-range functional connectivity strength (FCS) analysis indicated that before
      transplantation both noHE and HE groups showed diffuse FCS abnormalities relative
      to healthy controls. For the noHE group, the abnormal FCS found before LT largely
      returned to normal levels after LT, except for in the cerebellum, precuneus, and
      orbital middle frontal gyrus. However, the abnormal FCS prior to LT was largely
      preserved in the HE group, including high-level cognition-related (frontal and
      parietal lobes) and vision-related areas (occipital lobe, cuneus, and precuneus).
      In addition, comparisons between HE and noHE groups revealed that weaker FCS in
      default mode network (DMN) in HE group persisted from pre- to post- LT.
      Correlation analysis showed that changes in FCS in the left postcentral and right
      middle frontal gyrus correlated with alterations in neuropsychological
      performance and ammonia levels. In conclusion, the findings in this study
      demonstrate potential adverse effects of pre-LT episode of HE on post-LT brain
      function recovery, and reveal that DMN may be the most affected brain region by
      HE episodes, which can't be reversed by LT.

PMID- 29170934
TI  - Pros and Cons of Character Portrayals of Autism on TV and Film.
AB  - Portrayals of characters with autism spectrum disorder (ASD) and/or with autistic
      traits on film and in TV-series are increasing. Such portrayals may contribute in
      increasing awareness of the condition but can also increase stereotypes. Thus,
      these character portrayals are subject to heated debate within the ASD-community,
      but also in the general public at large. Following our recent published study on
      character portrayals of ASD on film and TV we here address some central issues
      related advantages and disadvantage of such portrayals.

PMID- 29170935
TI  - Predicting Internalizing and Externalizing Symptoms in Children with ASD:
      Evaluation of a Contextual Model of Parental Factors.
AB  - Parental adjustment, parenting behaviors, and child routines have been linked to
      internalizing and externalizing child behavior. The purpose of the present study
      was to evaluate a comprehensive model examining relations among these variables
      in children with ASD and their parents. Based on Sameroff's Transactional Model
      of Development (Sameroff in: The transactional model of development: How children
      and contexts shape each other, American Psychological Association, Washington,
      DC, 2009), researchers hypothesized that these factors would collectively predict
      child behavior. Parents (n = 67) completed measures of parental adjustment,
      parenting behaviors, child routines, and child behavior using the Hopkins Symptom
      Checklist, Alabama Parenting Questionnaire, Child Routines Inventory, and Child
      Behavior Checklist, respectively. Results indicated that parental adjustment
      predicted harsh/disengaged parenting (B = 0.17, p < .01) and internalizing
      behavior (B = 0.32, p < .01). Harsh/disengaged parenting and warm/supportive
      parenting predicted externalizing behavior (B = 0.59, p < .01) and internalizing
      behavior (B = - 0.49 p < .01), respectively.

PMID- 29170936
TI  - Symbolic Play in School-Aged Minimally Verbal Children with Autism Spectrum
      Disorder.
AB  - Few interventions exist for school-aged minimally verbal children with autism
      spectrum disorder (ASD). Even though play skills are associated with children's
      production of language, few studies have focused on play for minimally verbal
      children. Fifty-eight minimally verbal children with ASD received a naturalistic
      developmental behavioral intervention. Children were randomized to receive a
      speech generating device in the context of the intervention or not. Children in
      both conditions improved in play skills at exit. Children demonstrated an
      increase in play skills in proximal (sessions) and distal (during blind
      assessment) contexts. Minimally verbal children with ASD can improve their play
      skills within a targeted intervention. Increases in symbolic play were associated
      with increases in expressive language skills.

PMID- 29170937
TI  - Commentary on Social Skills Training Curricula for Individuals with ASD: Social
      Interaction, Authenticity, and Stigma.
AB  - By teaching social rules thought to be necessary for social competence, social
      skills training (SST) curricula aim to improve indicators of well-being for
      individuals with autism spectrum disorder (ASD), such as the attainment of
      meaningful friendships. However, several recent meta-analyses indicate that SST
      curricula may fall short of these goals. We offer an explanation for these
      potentially null effects by illustrating how the content of these curricula
      diverge from empirical evidence derived from disciplines that take social
      interaction as their object of study. Next, we argue that employing the social
      rules advocated for by SST curricula may work counterproductively by inhibiting
      authenticity, while at the same time increasing stigma associated with ASD. We
      close with suggestions for future intervention research.

PMID- 29170938
TI  - Feasibility of Parent Training via Telehealth for Children with Autism Spectrum
      Disorder and Disruptive Behavior: A Demonstration Pilot.
AB  - Telehealth is a potential solution to limited access to specialized services for
      children with autism spectrum disorder (ASD) in rural areas. We conducted a
      feasibility trial of parent training with children ages 3-8 with ASD and
      disruptive behavior from rural communities. Fourteen children (mean age 5.8 +/-
      1.7) from four telehealth sites enrolled. Thirteen families (92.9%) completed
      treatment, with 91.6% of core sessions attended. Therapists attained 98% fidelity
      to the manual and 93% of expected outcome measures were collected at week 24.
      Eleven of 14 (78.6%) participants were rated as much/very much improved. Parent
      training via telehealth was acceptable to parents and treatment could be
      delivered reliably by therapists. Preliminary efficacy findings suggests further
      study is justified.

PMID- 29170939
TI  - Behavioral Outcomes of Specialized Psychiatric Hospitalization in the Autism
      Inpatient Collection (AIC): A Multisite Comparison.
AB  - Psychiatric hospitalization of children with autism spectrum disorder (ASD) is
      relatively common and occurs at a higher rate than in non-ASD youth. This study
      compared changes in the severity of serious problem behaviors in 350 youth with
      ASD enrolled in the autism inpatient collection during and after hospitalization
      in six specialized child psychiatry units. There was a significant reduction in
      serious problem behaviors from admission (aberrant behavior checklist
      irritability subscale M = 29.7, SD 9.6) to discharge (M = 15.0, SD 10.3) and 2
      month follow-up (M = 19.3, SD 10.3). Between discharge and 2-month follow-up,
      tantrum-like behaviors but not self-injurious behaviors increased slightly.
      Improvement in the severity of problem behaviors was not uniform across sites,
      even after controlling for measured site differences.

PMID- 29170940
TI  - Association of Autism Spectrum Disorders and Inflammatory Bowel Disease.
AB  - Autism spectrum disorders (ASD) and inflammatory bowel disease (IBD) both have
      multifactorial pathogenesis with an increasing number of studies demonstrating
      gut-brain associations. We aim to examine the association between ASD and IBD
      using strict classification criteria for IBD. We conducted a retrospective case
      cohort study using records from the Military Health System database with IBD
      defined as having one encounter with an ICD-9-CM diagnostic code for IBD and at
      least one outpatient prescription dispensed for a medication to treat IBD.
      Children with ASD were more likely to meet criteria for Crohn's disease (CD) and
      Ulcerative colitis (UC) compared to controls. This higher prevalence of CD and UC
      in children with ASD compared to controls confirms the association of ASD with
      IBD.

PMID- 29170941
TI  - A Sibling-Mediated Intervention for Children with Autism Spectrum Disorder: Using
      the Natural Language Paradigm (NLP).
AB  - We taught three typically developing siblings to occasion speech by implementing
      the Natural Language Paradigm (NLP) with their brothers with autism spectrum
      disorder (ASD). A non-concurrent multiple baseline design across children with
      ASD and sibling dyads was used. Ancillary behaviors of happiness, play, and joint
      attention for the children with ASD were recorded. Generalization of speech for
      the children with ASD across setting and peers was also measured. During
      baseline, the children with ASD displayed few target speech behaviors and the
      siblings inconsistently occasioned speech from their brothers. After sibling
      training, however, they successfully delivered NLP, and in turn, for two of the
      brothers with ASD, speech reached criterion. Implications of this research
      suggest the inclusion of siblings in interventions.

PMID- 29170942
TI  - Refractive Status and Amblyopia Risk Factors in Chinese Children with Autism
      Spectrum Disorder.
AB  - Amblyopia risk factors in children with autism spectrum disorders (ASD) are
      usually hard to detect in early childhood due to poor cooperation and has not
      been reported in the Chinese population. We screened 168 Chinese children with
      ASD, aged between 3 and 8 years, and 264 age-matched neurotypical children with
      Spot photoscreener and basic ophthalmologic examinations. Children with ASD were
      found to have normal refractive status but significantly higher incidence of
      strabismus (16.1%), compared with control children (1.5%) (p < 0.01). Most of the
      cases of strabismus found in children with ASD were classified as esodeviation.
      Strabismus in children with ASD should be considered more seriously as an
      amblyopia risk factor by ophthalmologists and other healthcare professionals.

PMID- 29170943
TI  - Asenapine Treatment in Pediatric Patients with Bipolar I Disorder or
      Schizophrenia: A Review.
AB  - Asenapine, administered as a twice-daily (BID) sublingual tablet, is approved in
      the US as monotherapy for the acute treatment of manic and mixed episodes of
      bipolar I disorder in children and adolescents aged 10-17 years based on the
      positive results of one 3-week, double-blind, placebo-controlled study; the
      recommended dose is 2.5-10 mg BID. Although asenapine has been studied in
      pediatric patients with schizophrenia, it is not approved for this indication.
      Asenapine is not approved for pediatric use in bipolar I disorder or
      schizophrenia in other major markets. To inform clinicians treating psychiatric
      disorders in pediatric patients, we have summarized the neuropharmacology,
      pharmacokinetics, clinical trial experience, and clinical use of asenapine in
      pediatric patients. After rapid absorption through the oral mucosa, the
      pharmacokinetic profile of asenapine in pediatric patients is similar to that
      which is observed in adult patients, indicating that the recommended adult dosage
      does not need to be adjusted for pediatric use. Intake of food and water should
      be avoided for 10 min after administration. In clinical trials, asenapine was
      generally safe and well tolerated in pediatric patients with bipolar I disorder
      and schizophrenia. Serious adverse effects were generally related to worsening of
      the underlying psychiatric disorder. The most common treatment-emergent adverse
      events (TEAEs) in both indications were sedation and somnolence. Like some other
      second-generation antipsychotic agents, weight gain and changes in some metabolic
      parameters were noted; oral effects (e.g., oral hypoesthesia, dysgeusia,
      paresthesia) related to sublingual administration did not typically result in
      treatment discontinuation and were generally transient. Extrapyramidal symptom
      TEAEs occurred in >=5% of asenapine-treated patients in the acute and long-term
      studies in bipolar I disorder and schizophrenia.

PMID- 29170944
TI  - Deep TMS of the insula using the H-coil modulates dopamine release: a crossover
      [11C] PHNO-PET pilot trial in healthy humans.
AB  - : Modulating the function of the insular cortex could be a novel therapeutic
      strategy to treat addiction to a variety of drugs of abuse as this region has
      been implicated in mediating drug reward and addictive processes. The recent
      advent of the H-coil has permitted the targeting of deeper brain structures which
      was not previously feasible. The goal of this study was to bilaterally target the
      insular region using the H-coil with repetitive Transcranial Magnetic Stimulation
      (rTMS) and subsequently measure changes in dopamine levels using Positron
      Emission Tomography (PET) with [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO).
      This was a within-subject, crossover, blinded and sham-controlled pilot study.
      Eight healthy, right-handed subjects, aged 19-45, participated in the
      investigation. All subjects underwent 3 PHNO-PET scans preceded by rTMS (sham, 1
      Hz or 10 Hz), on 3 separate days. Low frequency rTMS (1 Hz), targeting the
      insular cortex, significantly decreased dopamine levels in the substantia nigra,
      sensorimotor striatum and associative striatum. Replicating this study in tobacco
      smokers or alcoholics would be a logical follow-up to assess whether H-coil
      stimulation of the bilateral insula can be employed as a treatment option for
      addiction. TRIAL REGISTRATION: NCT02212405.

PMID- 29170947
TI  - Disclosure and Stigma of a Positive HIV-Serostatus: A Two-Step Cluster Analysis
      of the HIV Disclosure Scale.
AB  - Despite national efforts to improve the public's education about an HIV
      diagnosis, stigma still plays a significant role in how persons living with HIV
      (PLH) decide to disclose their serostatus to friends, family, or healthcare
      workers. Disclosure can be related to both positive and negative psychological
      health outcomes, including rates of depression and perceived social support.
      Researchers often assess disclosure patterns in PLH due to its association with
      important health implications; however, to date, there are no empirically
      validated measures of HIV-serostatus disclosure. The HIV Disclosure Scale (HDS)
      was created to assess various aspects of the disclosure process and has been
      utilized in several studies as an adequate measurement of HIV-serostatus
      disclosure despite no available psychometric data. This study aims to uncover
      constructs measured by the HDS using exploratory two-step cluster analysis to
      provide an initial analysis of the psychometric properties of this scale.

PMID- 29170946
TI  - Contraceptive Use Among HIV-Infected Females with History of Injection Drug Use
      in St. Petersburg, Russia.
AB  - Limited research examines family planning for HIV-infected women with a history
      of injection drug use. We describe modern contraceptive use and its association
      with heavy drinking and recent injection for HIV-infected females in St.
      Petersburg, Russia (N = 49): 22.4% (n = 11) used traditional methods and 30.6% (n
      = 15) reported modern contraceptive use, which consisted primarily of condoms
      (26.5%, n = 13). Over 63% (n = 31) had an abortion. Observed associations for
      heavy alcohol use (AOR = 2.36, CI = 0.53, 12.41) and recent injection drug use
      (AOR = 2.88, CI = 0.60, 16.92) were clinically notable, but not statistically
      significant. Prioritizing family planning for HIV-infected women with a history
      of substance use is urgently needed.

PMID- 29170945
TI  - Sex Practices by HIV Awareness and Engagement in the Continuum of Care Among MSM:
      A National HIV Behavioral Surveillance Analysis in 21 U.S. Cities.
AB  - Using National HIV Behavioral Surveillance (NHBS) cross-sectional survey and HIV
      testing data in 21 U.S. metropolitan areas, we identify sex practices among
      sexually active men who have sex with men (MSM) associated with: (1) awareness of
      HIV status, and (2) engagement in the HIV care continuum. Data from 2008, 2011,
      and 2014 were aggregated, yielding a sample of 5079 sexually active MSM living
      with HIV (MLWH). Participants were classified into HIV status categories: (1)
      unaware; (2) aware and out of care; (3) aware and in care without antiretroviral
      therapy (ART); and (4) aware and on ART. Analyses were conducted examining sex
      practices (e.g. condomless sex, discordant condomless sex, and number of sex
      partners) by HIV status. Approximately 30, 5, 10 and 55% of the sample was
      classified as unaware, aware and out of care, aware and in care without ART, and
      aware and on ART, respectively. Unaware MLWH were more likely to report
      condomless anal sex with a last male partner of discordant or unknown HIV status
      (25.9%) than aware MLWH (18.0%, p value < 0.0001). Unaware MLWH were 3 times as
      likely to report a female sex partner in the prior 12 months as aware MLWH (17.3
      and 5.6%, p-value < 0.0001). When examining trends across the continuum of care,
      reports of any condomless anal sex with a male partner in the past year (ranging
      from 65.0 to 70.0%), condomless anal sex with a male partner of discordant or
      unknown HIV status (ranging from 17.7 to 21.3%), and median number of both male
      and female sex partners were similar. In conclusion, awareness of HIV and
      engagement in care was not consistently associated with protective sex practices,
      highlighting the need for continued prevention efforts.

PMID- 29170948
TI  - Probabilistic assessment of phenophase-wise agricultural drought risk under
      different sowing windows: a case study with rainfed soybean.
AB  - A new methodology for crop-growth stage-specific assessment of agricultural
      drought risk under a variable sowing window is proposed for the soybean crop. It
      encompasses three drought indices, which include Crop-Specific Drought Index
      (CSDI), Vegetation Condition Index (VCI), and Standardized Precipitation
      Evapotranspiration Index (SPEI). The unique features of crop-growth stage
      specific nature and spatial and multi-scalar coverage provide a comprehensive
      assessment of agricultural drought risk. This study was conducted in 10 major
      soybean-growing districts of Madhya Pradesh state of India. These areas
      contribute about 60% of the total soybean production for the country. The
      phenophase most vulnerable to agricultural drought was identified (germination
      and flowering in our case) for each district across four sowing windows. The
      agricultural drought risk was quantified at various severity levels (moderate,
      severe, and very severe) for each growth stage and sowing window. Validation of
      the proposed new methodology also yielded results with a high correlation
      coefficient between percent probability of agricultural drought risk and yield
      risk (r = 0.92). Assessment by proximity matrix yielded a similar statistic.
      Expectations for the proposed methodology are better mitigation-oriented
      management and improved crop contingency plans for planners and decision makers.

PMID- 29170949
TI  - Parts Characterization for Tunable Protein Expression.
AB  - Flow-seq combines flexible genome engineering methods with flow cytometry-based
      cell sorting and deep DNA sequencing to enable comprehensive interrogation of
      genotype to phenotype relationships. One application is to study the effect of
      specific regulatory elements on protein expression. Constructing targeted genomic
      variation around genomically integrated fluorescent marker genes enables rapid
      elucidation of the contribution of specific sequence variants to protein
      expression. Such an approach can be used to characterize the impact of
      modifications to the Shine-Dalgarno sequence in Escherichia coli.

PMID- 29170950
TI  - Enzyme Nicotinamide Cofactor Specificity Reversal Guided by Automated Structural
      Analysis and Library Design.
AB  - The specificity of enzymes for nicotinamide adenine dinucleotide (NAD) or
      nicotinamide adenine dinucleotide phosphate (NADP) as redox carriers can pose a
      significant hurdle for metabolic engineering and synthetic biology applications,
      where switching the specificity might be beneficial. We have developed an easy-to
      use computational tool (CSR-SALAD) for the design of mutant libraries to simplify
      the process of reversing the cofactor specificity of an enzyme. Here, we describe
      the optimal use of this tool and present methods for its application in a
      laboratory setting.

PMID- 29170951
TI  - Bacterial Genome Editing Strategy for Control of Transcription and Protein
      Stability.
AB  - In molecular biology and cell factory engineering, tools that enable control of
      protein production and stability are highly important. Here, we describe
      protocols for tagging genes in Escherichia coli allowing for inducible
      degradation and transcriptional control of any soluble protein of interest. The
      underlying molecular biology is based on the two cross-kingdom tools CRISPRi and
      the N-end rule for protein degradation. Genome editing is performed with the
      CRMAGE technology and randomization of the translational initiation region
      minimizes the polar effects of tag insertion. The approach has previously been
      applied for targeting proteins originating from essential operon-located genes
      and has potential to serve as a universal synthetic biology tool.

PMID- 29170952
TI  - An Automated Pipeline for Engineering Many-Enzyme Pathways: Computational
      Sequence Design, Pathway Expression-Flux Mapping, and Scalable Pathway
      Optimization.
AB  - Engineering many-enzyme metabolic pathways suffers from the design curse of
      dimensionality. There are an astronomical number of synonymous DNA sequence
      choices, though relatively few will express an evolutionary robust, maximally
      productive pathway without metabolic bottlenecks. To solve this challenge, we
      have developed an integrated, automated computational-experimental pipeline that
      identifies a pathway's optimal DNA sequence without high-throughput screening or
      many cycles of design-build-test. The first step applies our Operon Calculator
      algorithm to design a host-specific evolutionary robust bacterial operon sequence
      with maximally tunable enzyme expression levels. The second step applies our RBS
      Library Calculator algorithm to systematically vary enzyme expression levels with
      the smallest-sized library. After characterizing a small number of constructed
      pathway variants, measurements are supplied to our Pathway Map Calculator
      algorithm, which then parameterizes a kinetic metabolic model that ultimately
      predicts the pathway's optimal enzyme expression levels and DNA sequences.
      Altogether, our algorithms provide the ability to efficiently map the pathway's
      sequence-expression-activity space and predict DNA sequences with desired
      metabolic fluxes. Here, we provide a step-by-step guide to applying the Pathway
      Optimization Pipeline on a desired multi-enzyme pathway in a bacterial host.

PMID- 29170953
TI  - Computational Approaches on Stoichiometric and Kinetic Modeling for Efficient
      Strain Design.
AB  - Engineering biological systems that are capable of overproducing products of
      interest is the ultimate goal of any biotechnology application. To this end,
      stoichiometric (or steady state) and kinetic models are increasingly becoming
      available for a variety of organisms including prokaryotes, eukaryotes, and
      microbial communities. This ever-accelerating pace of such model reconstructions
      has also spurred the development of optimization-based strain design techniques.
      This chapter highlights a number of such frameworks developed in recent years in
      order to generate testable hypotheses (in terms of genetic interventions), thus
      addressing the challenges in metabolic engineering. In particular, three major
      methods are covered in detail including two methods for designing strains (i.e.,
      one stoichiometric model-based and the other by integrating kinetic information
      into a stoichiometric model) and one method for analyzing microbial communities.

PMID- 29170954
TI  - Extended Metabolic Space Modeling.
AB  - Determining the fraction of the chemical space that can be processed in vivo by
      using natural and synthetic biology devices is crucial for the development of
      advanced synthetic biology applications. The extended metabolic space is a coding
      system based on molecular signatures that enables the derivation of reaction
      rules for metabolic reactions and the enumeration of all possible substrates and
      products corresponding to the rules. The extended metabolic space expands
      capabilities for controlling the production, processing, sensing, and the release
      of specific molecules in chassis organisms.

PMID- 29170955
TI  - Computational Methods to Assess the Production Potential of Bio-Based Chemicals.
AB  - Elevated costs and long implementation times of bio-based processes for producing
      chemicals represent a bottleneck for moving to a bio-based economy. A prospective
      analysis able to elucidate economically and technically feasible product targets
      at early research phases is mandatory. Computational tools can be implemented to
      explore the biological and technical spectrum of feasibility, while constraining
      the operational space for desired chemicals. In this chapter, two different
      computational tools for assessing potential for bio-based production of chemicals
      from different perspectives are described in detail. The first tool is GEM-Path:
      an algorithm to compute all structurally possible pathways from one target
      molecule to the host metabolome. The second tool is a framework for Modeling
      Sustainable Industrial Chemicals production (MuSIC), which integrates modeling
      approaches for cellular metabolism, bioreactor design, upstream/downstream
      processes, and economic impact assessment. Integrating GEM-Path and MuSIC will
      play a vital role in supporting early phases of research efforts and guide the
      policy makers with decisions, as we progress toward planning a sustainable
      chemical industry.

PMID- 29170956
TI  - Multiplex Genome Editing in Escherichia coli.
AB  - Lambda Red recombineering is an easy and efficient method for generating genetic
      modifications in Escherichia coli. For gene deletions, lambda Red recombineering
      is combined with the use of selectable markers, which are removed through the
      action of, e.g., flippase (Flp) recombinase. This PCR-based engineering method
      has also been applied to a number of other bacteria. In this chapter, we describe
      a recently developed one plasmid-based method as well as the use of a strain with
      genomically integrated recombineering genes, which significantly speeds up the
      engineering of strains with multiple genomic alterations.

PMID- 29170957
TI  - Designing and Implementing Algorithmic DNA Assembly Pipelines for Multi-Gene
      Systems.
AB  - Advances in DNA synthesis and assembly technology allow for the high-throughput
      fabrication of hundreds to thousands of multi-part genetic constructs in a short
      time. This allows for rapid hypothesis-testing and genetic optimization in multi
      gene biological systems. Here, we discuss key considerations to design and
      implement an algorithmic DNA assembly pipeline that provides the freedom to
      change nearly any design variable in a multi-gene system. In addition to
      considerations for pipeline design, we describe protocols for three useful
      molecular biology techniques in plasmid construction.

PMID- 29170958
TI  - An Adaptive Laboratory Evolution Method to Accelerate Autotrophic Metabolism.
AB  - Adaptive laboratory evolution (ALE) is an approach enabling the development of
      novel characteristics in microbial strains via the application of a constant
      selection pressure. This method is also an efficient tool to acquire insights on
      molecular mechanisms responsible for specific phenotypes. ALE experiments have
      mainly been conducted with heterotrophic microbes to study, for instance, cell
      metabolism with different multicarbon substrates, tolerance to solvents, pH
      variation, and high temperature. Here, we describe employing an ALE method to
      generate Sporomusa ovata strains growing faster autotrophically and reducing CO2
      into acetate more efficiently. Strains developed via this ALE method were also
      used to gain knowledge on the autotrophic metabolism of S. ovata as well as other
      acetogenic bacteria.

PMID- 29170959
TI  - CRISPR-Cas9 Toolkit for Actinomycete Genome Editing.
AB  - Bacteria of the order Actinomycetales are one of the most important sources of
      bioactive natural products, which are the source of many drugs. However, many of
      them still lack efficient genome editing methods, some strains even cannot be
      manipulated at all. This restricts systematic metabolic engineering approaches
      for boosting known and discovering novel natural products. In order to facilitate
      the genome editing for actinomycetes, we developed a CRISPR-Cas9 toolkit with
      high efficiency for actinomyces genome editing. This basic toolkit includes a
      software for spacer (sgRNA) identification, a system for in-frame gene/gene
      cluster knockout, a system for gene loss-of-function study, a system for
      generating a random size deletion library, and a system for gene knockdown. For
      the latter, a uracil-specific excision reagent (USER) cloning technology was
      adapted to simplify the CRISPR vector construction process. The application of
      this toolkit was successfully demonstrated by perturbation of genomes of
      Streptomyces coelicolor A3(2) and Streptomyces collinus Tu 365. The CRISPR-Cas9
      toolkit and related protocol described here can be widely used for metabolic
      engineering of actinomycetes.

PMID- 29170960
TI  - Assembly and Multiplex Genome Integration of Metabolic Pathways in Yeast Using
      CasEMBLR.
AB  - Genome integration is a vital step for implementing large biochemical pathways to
      build a stable microbial cell factory. Although traditional strain construction
      strategies are well established for the model organism Saccharomyces cerevisiae,
      recent advances in CRISPR/Cas9-mediated genome engineering allow much higher
      throughput and robustness in terms of strain construction. In this chapter, we
      describe CasEMBLR, a highly efficient and marker-free genome engineering method
      for one-step integration of in vivo assembled expression cassettes in multiple
      genomic sites simultaneously. CasEMBLR capitalizes on the CRISPR/Cas9 technology
      to generate double-strand breaks in genomic loci, thus prompting native
      homologous recombination (HR) machinery to integrate exogenously derived homology
      templates. As proof-of-principle for microbial cell factory development, CasEMBLR
      was used for one-step assembly and marker-free integration of the carotenoid
      pathway from 15 exogenously supplied DNA parts into three targeted genomic loci.
      As a second proof-of-principle, a total of ten DNA parts were assembled and
      integrated in two genomic loci to construct a tyrosine production strain, and at
      the same time knocking out two genes. This new method complements and improves
      the field of genome engineering in S. cerevisiae by providing a more flexible
      platform for rapid and precise strain building.

PMID- 29170961
TI  - A Modified Gibson Assembly Method for Cloning Large DNA Fragments with High GC
      Contents.
AB  - Gibson one-step, isothermal assembly method (Gibson assembly) can be used to
      efficiently assemble large DNA molecules by in vitro recombination involving a 5'
      exonuclease, a DNA polymerase and a DNA ligase. In the past few years, this
      robust DNA assembly method has been widely applied to seamlessly construct genes,
      genetic pathways and even entire genomes. Here, we expand this method to clone
      large DNA fragments with high GC contents, such as antibiotic biosynthetic gene
      clusters from Streptomyces . Due to the low isothermal condition (50  degrees C)
      in the Gibson reaction system, the complementary overlaps with high GC contents
      are proposed to easily form mismatched linker pairings, which leads to low
      assembly efficiencies mainly due to vector self-ligation. So, we modified this
      classic method by the following two steps. First, a pair of universal terminal
      single-stranded DNA overhangs with high AT contents are added to the ends of the
      BAC vector. Second, two restriction enzyme sites are introduced into the
      respective sides of the designed overlaps to achieve the hierarchical assembly of
      large DNA molecules. The optimized Gibson assembly method facilitates fast
      acquisition of large DNA fragments with high GC contents from Streptomyces.

PMID- 29170962
TI  - Coupling Yeast Golden Gate and VEGAS for Efficient Assembly of the Violacein
      Pathway in Saccharomyces cerevisiae.
AB  - The ability to express non-native pathways in genetically tractable model systems
      is important for fields such as synthetic biology, genetics, and metabolic
      engineering. Here we describe a modular and hierarchical strategy to assemble
      multigene pathways for expression in S. cerevisiae. First, discrete promoter,
      coding sequence, and terminator parts are assembled in vitro into Transcription
      Units (TUs) flanked by adapter sequences using "yeast Golden Gate" (yGG), a type
      IIS restriction enzyme-dependent cloning strategy. Next, harnessing the natural
      capacity of S. cerevisiae for homologous recombination, TUs are assembled into
      pathways and expressed using the "Versatile Genetic Assembly System" (VEGAS) in
      yeast. Coupling transcription units constructed by yGG with VEGAS assembly is a
      generic and flexible workflow to achieve pathway expression in S. cerevisiae.
      This protocol describes assembly of a five TU pathway for yeast production of
      violacein, a pigment derived from Chromobacterium violaceum.

PMID- 29170963
TI  - Multi-capillary Column Ion Mobility Spectrometry of Volatile Metabolites for
      Phenotyping of Microorganisms.
AB  - Rational strain engineering requires solid testing of phenotypes including
      productivity and ideally contributes thereby directly to our understanding of the
      genotype-phenotype relationship. Actually, the test step of the strain
      engineering cycle becomes the limiting step, as ever advancing tools for
      generating genetic diversity exist. Here, we briefly define the challenge one
      faces in quantifying phenotypes and summarize existing analytical techniques that
      partially overcome this challenge. We argue that the evolution of volatile
      metabolites can be used as proxy for cellular metabolism. In the simplest case,
      the product of interest is a volatile (e.g., from bulk alcohols to special
      fragrances) that is directly quantified over time. But also nonvolatile products
      (e.g., from bulk long-chain fatty acids to natural products) require major flux
      rerouting that result potentially in altered volatile production. While
      alternative techniques for volatile determination exist, rather few can be
      envisaged for medium to high-throughput analysis required for phenotype testing.
      Here, we contribute a detailed protocol for an ion mobility spectrometry (IMS)
      analysis that allows volatile metabolite quantification down to the ppb range.
      The sensitivity can be exploited for small-scale fermentation monitoring. The
      insights shared might contribute to a more frequent use of IMS in biotechnology,
      while the experimental aspects are of general use for researchers interested in
      volatile monitoring.

PMID- 29170964
TI  - Selection of Highly Expressed Gene Variants in Escherichia coli Using
      Translationally Coupled Antibiotic Selection Markers.
AB  - Strategies to select highly expressed variants of a protein coding sequence are
      usually based on trial-and-error approaches, which are time-consuming and
      expensive. We address this problem using translationally coupled antibiotic
      resistance markers. The system requires that the target gene can be fused at the
      3'-end with a translational coupling element and an antibiotic resistance gene.
      Highly expressed target genes can then be selected using a fast and simple whole
      cell survival assay in the presence of high antibiotic concentrations. Herein we
      show that the system can be used to select highly expressing clones from
      libraries sampling translation initiation sites.

PMID- 29170965
TI  - Design, Engineering, and Characterization of Prokaryotic Ligand-Binding
      Transcriptional Activators as Biosensors in Yeast.
AB  - In cell factory development, screening procedures, often relying on low
      throughput analytical methods, are lagging far behind diversity generation
      methods. This renders the identification and selection of the best cell factory
      designs tiresome and costly, conclusively hindering the manufacturing process. In
      the yeast Saccharomyces cerevisiae, implementation of allosterically regulated
      transcription factors from prokaryotes as metabolite biosensors has proven a
      valuable strategy to alleviate this screening bottleneck. Here, we present a
      protocol to select and incorporate prokaryotic transcriptional activators as
      metabolite biosensors in S. cerevisiae. As an example, we outline the engineering
      and characterization of the LysR-type transcriptional regulator (LTTR) family
      member BenM from Acetinobacter sp. ADP1 for monitoring accumulation of cis,cis
      muconic acid, a bioplast precursor, in yeast by means of flow cytometry.

PMID- 29170966
TI  - A Capture-SELEX Strategy for Multiplexed Selection of RNA Aptamers Against Small
      Molecules.
AB  - In vitro selection of aptamers that recognize small organic molecules has proven
      difficult, in part due to the challenge of immobilizing small molecules on solid
      supports for SELEX (Systematic Evolution of Ligands by Exponential Enrichment).
      This study describes the implementation of RNA Capture-SELEX, a selection
      strategy that uses an RNA library to yield ligand-responsive RNA aptamers
      targeting small organic molecules in solution. To demonstrate the power of this
      method we selected several aptamers with specificity towards either the natural
      sweetener rebaudioside A or the food-coloring agent carminic acid. In addition,
      Bio-layer interferometry is used to screen clonal libraries of aptamer candidates
      and is used to interrogate aptamer affinity. The RNA-based Capture-SELEX strategy
      described here simplifies selection of RNA aptamers against small molecules by
      avoiding ligand immobilization, while also allowing selection against multiple
      candidate targets in a single experiment. This makes RNA Capture-SELEX
      particularly attractive for accelerated development of RNA aptamers targeting
      small metabolites for incorporation into synthetic riboswitches and for
      analytical biosensors.

PMID- 29170967
TI  - High-Throughput Microfluidics for the Screening of Yeast Libraries.
AB  - Cell factory development is critically important for efficient biological
      production of chemicals, biofuels, and pharmaceuticals. Many rounds of the Design
      Build-Test-Learn cycles may be required before an engineered strain meeting
      specific metrics required for industrial application. The bioindustry prefer
      products in secreted form (secreted products or extracellular metabolites) as it
      can lower the cost of downstream processing, reduce metabolic burden to cell
      hosts, and allow necessary modification on the final products , such as
      biopharmaceuticals. Yet, products in secreted form result in the disconnection of
      phenotype from genotype, which may have limited throughput in the Test step for
      identification of desired variants from large libraries of mutant strains. In
      droplet microfluidic screening, single cells are encapsulated in individual
      droplet and enable high-throughput processing and sorting of single cells or
      clones. Encapsulation in droplets allows this technology to overcome the
      throughput limitations present in traditional methods for screening by
      extracellular phenotypes. In this chapter, we describe a protocol/guideline for
      high-throughput droplet microfluidics screening of yeast libraries for higher
      protein secretion . This protocol can be adapted to screening by a range of other
      extracellular products from yeast or other hosts.

PMID- 29170968
TI  - Growth-Coupled Carotenoids Production Using Adaptive Laboratory Evolution.
AB  - Adaptive laboratory evolution is a powerful technique for strain development.
      However, the target phenotypes using this strategy have been limited by the
      required coupling of the phenotype-of-interest with fitness or survival, and thus
      adaptive evolution is generally not used to improve product formation. If the
      desired product confers a benefit to the host, then adaptive evolution can be an
      effective approach to improve host productivity. In this book chapter, we
      describe an effective adaptive laboratory evolution strategy for improving
      product formation of carotenoids, a class of compounds with antioxidant
      potential, in the yeast Saccharomyces cerevisiae.

PMID- 29170969
TI  - Two-Scale 13C Metabolic Flux Analysis for Metabolic Engineering.
AB  - Accelerating the Design-Build-Test-Learn (DBTL) cycle in synthetic biology is
      critical to achieving rapid and facile bioengineering of organisms for the
      production of, e.g., biofuels and other chemicals. The Learn phase involves using
      data obtained from the Test phase to inform the next Design phase. As part of the
      Learn phase, mathematical models of metabolic fluxes give a mechanistic level of
      comprehension to cellular metabolism, isolating the principle drivers of
      metabolic behavior from the peripheral ones, and directing future experimental
      designs and engineering methodologies. Furthermore, the measurement of
      intracellular metabolic fluxes is specifically noteworthy as providing a rapid
      and easy-to-understand picture of how carbon and energy flow throughout the cell.
      Here, we present a detailed guide to performing metabolic flux analysis in the
      Learn phase of the DBTL cycle, where we show how one can take the isotope
      labeling data from a 13C labeling experiment and immediately turn it into a
      determination of cellular fluxes that points in the direction of genetic
      engineering strategies that will advance the metabolic engineering process.For
      our modeling purposes we use the Joint BioEnergy Institute (JBEI) Quantitative
      Metabolic Modeling (jQMM) library, which provides an open-source, python-based
      framework for modeling internal metabolic fluxes and making actionable
      predictions on how to modify cellular metabolism for specific bioengineering
      goals. It presents a complete toolbox for performing different types of flux
      analysis such as Flux Balance Analysis, 13C Metabolic Flux Analysis, and it
      introduces the capability to use 13C labeling experimental data to constrain
      comprehensive genome-scale models through a technique called two-scale 13C
      Metabolic Flux Analysis (2S-13C MFA) [1]. In addition to several other
      capabilities, the jQMM is also able to predict the effects of knockouts using the
      MoMA and ROOM methodologies. The use of the jQMM library is illustrated through a
      step-by-step demonstration, which is also contained in a digital Jupyter Notebook
      format that enhances reproducibility and provides the capability to be adopted to
      the user's specific needs. As an open-source software project, users can modify
      and extend the code base and make improvements at will, providing a base for
      future modeling efforts.

PMID- 29170970
TI  - Smartphones in clinical practice: doctors' experience at two Dublin paediatric
      teaching hospitals.
AB  - INTRODUCTION: We conducted a study at two main centres for paediatric surgery in
      the Republic of Ireland, Temple Street Children's University Hospital (TSCUH) and
      Our Lady's Children's Hospital Crumlin (OLCHC). AIM: The aim of the study was to
      assess doctors' opinions, frequency and methods of smartphone use in clinical
      practice. METHODS: Doctors (n = 265) at the two hospitals were invited to
      complete a 12-item survey. Descriptive statistics were calculated accordingly.
      RESULTS: Almost 50% (132/256) responded; 98.4% owned a smartphone and 76% owned
      an iPhone. Seventy-nine percent used medical apps and 59% used the OLCHC
      formulary. Ninety-seven percent used smartphones for inter-team communication
      with 73.5% (n = 97) using WhatsApp. Smartphone camera was used by 57% for
      clinical photos and 41% for photos of radiological imaging. Only 42% reported
      obtaining consent for smartphone camera use from patients or guardians. Ninety
      two percent either 'strongly agreed' or 'agreed' that smartphones positively
      impact their practice. CONCLUSION: Smartphone usage is universal among healthcare
      professionals and their influence is growing in patient care.

PMID- 29170972
TI  - The accessibility and utilization of genetic testing for inherited heart rhythm
      disorders: a Canadian cross-sectional survey study.
AB  - The genetic basis of many sudden death-related conditions has been elucidated.
      These include inherited arrhythmias and arrhythmogenic cardiomyopathies, termed
      inherited heart rhythm disorders (IHRD). Advising on and interpreting genetic
      testing is challenging for the general cardiologist. This has led to the
      development of interdisciplinary clinics for IHRD in varying stages of
      establishment in Canada. We sought the viewpoints and patterns of practice of
      Canadian IHRD experts, and assessed their ability to access genetic testing for
      IHRD using a national cross-sectional survey. Of 56 participants, most were
      physicians (68%) or genetic counselors (19%). Despite working collaboratively,
      most genetic counselors (59%) were either not satisfied or only somewhat
      satisfied with their relationships with physicians. Ninety percent of
      participants were involved in offering genetic evaluation, including 80% who felt
      that testing was usually/always accessible. Most offered genetic testing to
      confirm clinical diagnosis and/or direct family screening. Post-mortem genetic
      analysis was sought by 69% of respondents; however, a lack of retained tissue
      and/or poor tissue preparation hindered this process. Family screening was
      usually recommended in the setting of a pathogenic/likely pathogenic variant. The
      most commonly perceived barrier to genetic testing was cost to the healthcare
      system. More than a quarter of patients waited >= 6 months for funding. An
      ability to engage at-risk relatives was rated as limited/poor by 34% of
      participants. Despite the establishment of several interdisciplinary clinics,
      timely access to affordable testing, supported by strong team communication,
      continues to be a barrier to genetic testing in Canada.

PMID- 29170971
TI  - Assembly and remodeling of viral DNA and RNA replicons regulated by cellular
      molecular chaperones.
AB  - A variety of cellular reactions mediated by interactions among proteins and
      nucleic acids requires a series of proteins called molecular chaperones. The
      viral genome encodes relatively few kinds of viral proteins and, therefore, host
      derived cellular factors are required for virus proliferation. Here we discuss
      those cellular proteins known as molecular chaperones, which are essential for
      the assembly of functional viral DNA/RNA replicons. The function of these
      molecular chaperones in the cellular context is also discussed.

PMID- 29170973
TI  - Primary acute angle-closure glaucoma complicating ciliochoroidal detachment:
      report of four cases and review of the literature.
AB  - PURPOSE: To describe the ultrasound biomicroscopy (UBM) and B-scan
      ultrasonography findings and therapeutic approach for ciliochoroidal detachment
      secondary to acute primary angle-closure glaucoma (APACG) in four patients. We
      also reviewed the literature. METHODS: Case report and systematic literature
      review. RESULTS: The four patients were referred to our department for further
      management of APACG. The UBM and B-scan ultrasonography examinations were
      conducted 2 days after the beginning of medical treatment and demonstrated
      ciliochoroidal detachment in four eyes of the four patients. The patients all
      received intravenous infusion of corticosteroid therapy (10 mg dexamethasone once
      daily for 5-7 days). We reviewed the UBM findings, which confirmed that the
      ciliochoroidal detachment disappeared. The patients then underwent trabeculectomy
      combined with peripheral iridotomy surgery. The patients all ultimately recovered
      very well. CONCLUSION: APACG with ciliochoroidal detachment is rare and has
      hidden clinical manifestations, and the pathophysiological mechanism is not yet
      fully understood. Anti-glaucoma surgery may increase the detachment. UBM and B
      scan ultrasounds are useful tools for ciliochoroidal detachment diagnosis in
      APACG patients before operative treatment.

PMID- 29170974
TI  - Comparative proteomic analysis of amnion membrane transplantation and cross
      linking treatments in an experimental alkali injury model.
AB  - PURPOSE: In this study, by using a two-dimensional (2D) electrophoresis-based
      experimental approach, we aimed at understanding the nature of alkali injuries
      and the underlying mechanisms. A secondary aim was to compare the effects of
      cross-linking (CXL) and amnion membrane transplantation (AMT) on corneal protein
      compositions at the end of the early repair phase after injured with alkali.
      METHOD: The right corneas of 24 rabbits were injured with a 1 N solution of NaOH.
      Groups were formed based on the adjuvant therapies as (1) healthy group, (2)
      control group, (3) CXL group, (4) AMT group. In addition to the therapies, a
      conventional medical treatment was applied to all groups. Left eyes were used as
      within-subject healthy corneas (1). The corneas were excised at day 21, and a
      comparative proteomic analysis was performed using 2D gel electrophoresis coupled
      with MALDI-TOF/TOF. RESULT: 2D gel electrophoresis revealed the presence seven
      protein spots whose abundance changed among the groups. Those proteins were SH3
      domain-binding protein, plant homeodomain finger protein 23, S100 calcium binding
      protein A-11(S100 A11), keratin type 2 cytoskeletal 1 and 2, transketolase and
      glyceraldehyde 3-phosphate dehydrogenase. Ingenuity pathway analysis predicted
      that the observed changes may be linked to a central metabolic pathway,
      transforming growth factor beta 1. Canonical pathway analysis focused our
      attention to two different pathways, namely nicotinamide adenine dinucleotide
      repair pathway and non-oxidative branch of pentose phosphate pathway. CONCLUSION:
      Our results shed some light onto the molecular mechanisms affected by alkali
      injury and adjuvant treatments. Further research is needed to propose medically
      significant target molecules that may be used for novel drug developments for
      alkali injury.

PMID- 29170975
TI  - Utility of superiorly based platysma myocutaneous flap for reconstruction of
      intraoral surgical defects: our experience.
AB  - PURPOSE: Various surgical modalities have been advocated for the soft tissue
      reconstruction of oral cavity with variable results. This prospective study
      evaluates the utility of platysma myocutaneous flap (PMF) in the reconstruction
      of surgical defects followed by treatment of oral submucous fibrosis (OSMF) and
      oral squamous cell carcinoma (OSCC) in terms of healing and functional outcomes.
      METHODS: In this prospective study, 47 patients with OSMF and 15 of OSCC were
      evaluated and selected for PMF reconstruction. OSCC was selected under T1N0M0
      category only. Patients were operated under general anaesthesia followed by PMF
      grafting. In OSCC, ipsilateral and for OSMF, bilateral PMF was used. RESULTS: In
      47 patients treated for OSMF, 46 were male and 1 female while 15 cases of OSCC,
      10 were male and 5 females aged between 18 and 44 years. Intraoperative mouth
      opening was achieved up to 48 mm in OSMF followed by 42.5 mm postoperatively
      after 2 years. However, uneventful healing and acceptable scar on cervical region
      was noted in all the cases including OSCC. In OSMF, three cases of dehiscence,
      four partial necrosis at end of flap and in OSCC one case shows skin loss at flap
      and two partial necrosis at tip of flap and extraoral localised abscess at
      ipsilateral donor site in one case was noted. An uneventful healing, anatomical
      form and functional results were restored with acceptable scarring at donor site
      without any evidence of difficulty in neck movements were observed. CONCLUSION:
      The PMF is simple, versatile and could be valued as a reconstructive alternative,
      with interesting visual qualities. It is a good therapeutic alternative tool for
      reconstruction of the buccal mucosa, especially for small- and medium-sized
      defects between 2 and 4 cm2 of the oral cavity.

PMID- 29170976
TI  - Real-world treatment in patients with HER2+ metastatic breast cancer : Treatment
      decisions in HER2+ mBC.
AB  - PURPOSE: The landscape of HER2+ metastatic breast cancer (mBC) treatment is
      changing due to the availability of new anti-HER2 drugs. The purpose of this
      study was to assess the current treatment patterns and sequences used in HER2+
      mBC in the real-world setting. Secondary objectives were to describe the factors
      that influence the decision to prescribe a first and second-line antitumour
      treatment. METHODS: Retrospective chart review of 3068 cases in Spain, Italy, the
      Netherlands and the UK. RESULTS: First and second-line treatments and regimens
      are consistent with the clinical guidelines, especially for recently initiated
      treatments. Age and performance status (PS) of patients impact treatment
      patterns: younger patients received more innovative treatments than elderly
      patients. In addition, while most patients received a first antitumor treatment,
      the rate of patients who continue to subsequent lines of therapy is low (55%
      transitioning from 1st to 2nd line; 58% from 2nd to 3rd line). Age and PS are key
      factors in the decision to prescribe further antitumor treatment. CONCLUSION:
      Fewer HER2+ mBC patients than expected receive a second and third line therapy.
      Guidelines should make specific recommendations for older patients or those with
      a poor PS.

PMID- 29170977
TI  - Species differences and mechanism of action of A3 adenosine receptor allosteric
      modulators.
AB  - Activity of the A3 adenosine receptor (AR) allosteric modulators LUF6000 (2
      cyclohexyl-N-(3,4-dichlorophenyl)-1H-imidazo [4,5-c]quinolin-4-amine) and LUF6096
      (N-{2-[(3,4-dichlorophenyl)amino]quinolin-4-yl}cyclohexanecarbox-amide) was
      compared at four A3AR species homologs used in preclinical drug development. In
      guanosine 5'-[gamma-[35S]thio]triphosphate ([35S]GTPgammaS) binding assays with
      cell membranes isolated from human embryonic kidney cells stably expressing
      recombinant A3ARs, both modulators substantially enhanced agonist efficacy at
      human, dog, and rabbit A3ARs but provided only weak activity at mouse A3ARs. For
      human, dog, and rabbit, both modulators increased the maximal efficacy of the
      A3AR agonist 2-chloro-N 6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide as well
      as adenosine > 2-fold, while slightly reducing potency in human and dog. Based on
      results from N 6-(4-amino-3-[125I]iodobenzyl)adenosine-5'-N-methylcarboxamide
      ([125I]I-AB-MECA) binding assays, we hypothesize that potency reduction is
      explained by an allosterically induced slowing in orthosteric ligand binding
      kinetics that reduces the rate of formation of ligand-receptor complexes.
      Mutation of four amino acid residues of the human A3AR to the murine sequence
      identified the extracellular loop 1 (EL1) region as being important in
      selectively controlling the allosteric actions of LUF6096 on [125I]I-AB-MECA
      binding kinetics. Homology modeling suggested interaction between species
      variable EL1 and agonist-contacting EL2. These results indicate that A3AR
      allostery is species-dependent and provide mechanistic insights into this
      therapeutically promising class of agents.

PMID- 29170978
TI  - Implementing a screening tool to improve prescribing in hospitalized older
      patients: a pilot study.
AB  - Background The use of STOPP-START criteria during hospitalization reduced
      inappropriate medications in randomized controlled trials. Objective To evaluate
      whether the implementation of a screening tool (short version of STOPP-START
      criteria) in routine geriatric practice reduces potentially inappropriate
      medications (PIM) and potential prescribing omissions (PPO) at discharge. Methods
      We conducted a retrospective interrupted time series analysis. Four periods were
      selected between February and September 2013: (1) baseline situation; (2)
      screening tool made available to physicians; (3) 3 months later; (4) weekly
      meetings with junior doctors and a clinical pharmacist to review treatments
      according to the tool. The primary outcome was the proportion of patients with
      prescribing improvement from admission to discharge. Results We included 120
      patients (median age 85 years). The prevalence of PIMs and PPOs on admission was
      56% (67/120) and 51% (61/120) respectively. Hospitalization improved prescribing
      appropriateness in 49% of patients with PIMs (33/67) and 39% of patients with
      PPOs (24/61). The use of the screening tool by way of multidisciplinary meetings
      was a predictor of PIMs reduction at discharge. Conclusions The sole distribution
      of a screening tool in a geriatric unit did not reduce PIMs and PPOs.
      Multidisciplinary meetings to review treatments should be encouraged.

PMID- 29170979
TI  - Predictors of changes in disease activity among children with juvenile
      dermatomyositis enrolled in the Childhood Arthritis and Rheumatology Research
      Alliance (CARRA) Legacy Registry.
AB  - Determinants of changes in disease activity among patients with juvenile
      dermatomyositis (JDM) are unknown. Our objective was to develop predictive models
      to predict changes in disease activity using the CARRA Legacy Registry. The CARRA
      Legacy Registry included 658 subjects with definite or probably JDM with 297
      subjects with a one follow-up visit after baseline, and we studied the 65
      subjects with active disease at baseline. Linear regression models were used to
      build risk scores for changes in disease activity adjusted for baseline disease
      activity, age, sex, and disease duration. Disease activity improved from baseline
      to 6-month follow-up as measured by patient/parent global health score (median 4;
      p = 0.008), patient pain score (median 2; p = 0.014), physician global (median 4;
      p < 0.001), and Childhood Myositis Assessment Scale (CMAS) (median 41, p <
      0.001). Anti-nuclear antibodies (p = 0.013) and hydroxychloroquine use (p =
      0.045) were significant predictors of less improvement in patient/parent global
      and baseline patient/parent global. Anti-nuclear antibodies (p = 0.001) and
      V/shawl sign (p = 0.005) were significant predictors of less improvement in
      patient pain (R-square improved from 0.29 for adjustors alone to 0.46 for the
      full model). Small joint arthritis (p < 0.01) predicted less improvement and
      dysphagia/dysphonia (p = 0.033) predicted greater improvement in CMAS and
      baseline CMAS (R-square improved from 0.73 for adjustors alone to 0.86 for the
      full model). Disease characteristics can help identify patients who are less
      likely to improve over time. Risk scores to predict future changes in disease
      activity could be used to trigger more aggressive treatment earlier in the
      disease course.

PMID- 29170980
TI  - From electromyographic activity to frequency modulation in zebra finch song.
AB  - Behavior emerges from the interaction between the nervous system and peripheral
      devices. In the case of birdsong production, a delicate and fast control of
      several muscles is required to control the configuration of the syrinx (the avian
      vocal organ) and the respiratory system. In particular, the syringealis ventralis
      muscle is involved in the control of the tension of the vibrating labia and thus
      affects the frequency modulation of the sound. Nevertheless, the translation of
      the instructions (which are electrical in nature) into acoustical features is
      complex and involves nonlinear, dynamical processes. In this work, we present a
      model of the dynamics of the syringealis ventralis muscle and the labia, which
      allows calculating the frequency of the generated sound, using as input the
      electrical activity recorded in the muscle. In addition, the model provides a
      framework to interpret inter-syllabic activity and hints at the importance of the
      biomechanical dynamics in determining behavior.

PMID- 29170982
TI  - Subcallosal and Heubner artery infarcts following surgical repair of an anterior
      communicating artery aneurysm: a causal relationship with postoperative amnesia
      and long-term outcome.
AB  - Since the 1950s, amnesia or memory impairment has been repeatedly reported in
      patients following surgical repair of anterior communicating artery (ACoA)
      aneurysms. Postoperative infarctions following surgical repair of ACoA aneurysms
      are classified as involvement of the subcallosal artery (the largest unpaired
      perforator of the ACoA), the recurrent artery of Heubner (RAH), or a combination
      of both. Postoperative amnesia can seriously affect the patient's quality of
      life, thus prompting physicians to discuss the symptomatology of the three
      infarction patterns. We made the following speculations regarding the causal
      relationship between the infarction pattern and postoperative amnesia. First,
      postoperative amnesia is most likely caused by an infarction in the territory of
      the subcallosal artery, particularly in the column of the fornix, a constituent
      of the Papez neuronal circuit. Second, infarction in the RAH territory alone is
      unlikely to cause significant amnesia. Third, infarcted foci in the RAH
      territory, when associated with a subcallosal artery infarction, can cause
      considerable frontal dysfunction due to impaired frontostriatal circuits in
      patients with postoperative amnesia, with resultant worsening of the long-term
      outcome or quality of life.

PMID- 29170983
TI  - Correlation of Age and Metabolic Adverse Effects of Antipsychotics.

PMID- 29170981
TI  - Natural Dietary Supplementation of Anthocyanins via PI3K/Akt/Nrf2/HO-1 Pathways
      Mitigate Oxidative Stress, Neurodegeneration, and Memory Impairment in a Mouse
      Model of Alzheimer's Disease.
AB  - Well-established studies have shown an elevated level of reactive oxygen species
      (ROS) that induces oxidative stress in the Alzheimer's disease (AD) patient's
      brain and an animal model of AD. Herein, we investigated the underlying anti
      oxidant neuroprotective mechanism of natural dietary supplementation of
      anthocyanins extracted from Korean black beans in the amyloid precursor
      protein/presenilin-1 (APP/PS1) mouse model of AD. Both in vivo (APP/PS1 mice) and
      in vitro (mouse hippocampal HT22 cells) results demonstrated that anthocyanins
      regulate the phosphorylated-phosphatidylinositol 3-kinase-Akt-glycogen synthase
      kinase 3 beta (p-PI3K/Akt/GSK3beta) pathways and consequently attenuate amyloid
      beta oligomer (AbetaO)-induced elevations in ROS level and oxidative stress via
      stimulating the master endogenous anti-oxidant system of nuclear factor erythroid
      2-related factor 2 (Nrf2) and heme oxygenase-1 (Nrf2/HO-1) pathways and prevent
      apoptosis and neurodegeneration by suppressing the apoptotic and
      neurodegenerative markers such as activation of caspase-3 and PARP-1 expression
      as well as the TUNEL and Fluoro-Jade B-positive neuronal cells in the APP/PS1
      mice. In vitro ApoTox-GloTM Triplex assay results also showed that anthocyanins
      act as a potent anti-oxidant neuroprotective agent and reduce AbetaO-induced
      neurotoxicity in the HT22 cells via PI3K/Akt/Nrf2 signaling. Importantly,
      anthocyanins improve memory-related pre- and postsynaptic protein markers and
      memory functions in the APP/PS1 mice. In conclusion, our data suggested that
      consumption and supplementation of natural-derived anti-oxidant neuroprotective
      agent such as anthocyanins may be beneficial and suggest new dietary-supplement
      strategies for intervention in and prevention of progressive neurodegenerative
      diseases, such as AD.

PMID- 29170984
TI  - Clinical nutrition and physical rehabilitation in a long-term care setting:
      preliminary observations in sarcopenic older patients.
AB  - BACKGROUND: Sarcopenia could have a negative prognostic impact in long-term care
      residents, which are characterized by multiple comorbidities and a high level of
      dependence. However, there is limited evidence on its prevalence and management
      in this healthcare setting. METHODS: All residents living in a long-term care
      institution were screened for the presence of sarcopenia. Sarcopenic patients in
      whom functional status could be assessed were included, based on the Tinetti
      scale (TS) score, in two parallel single-arm trials and received a specific
      nutritional supplement for muscle mass recovery in combination (TS >= 10) or not
      (TS < 10) with a supervised physical exercise rehabilitation program for 12
      months. The nutritional supplement was administered twice daily for the first 6
      months; none for 3 months and again twice daily for the last 3 months. RESULTS:
      We screened 95 residents and 81 had low skeletal muscle mass (SMM) according to
      bioimpedance. Thirty-nine residents were included in the intervention phase due
      to sarcopenia. At 6 months, patients receiving nutritional support alone (n = 17)
      showed a significant improvement in body weight (P = 0.009) and composition with
      an increase in SMM (from 15.3 +/- 4.1 to 17.0 +/- 5.1 kg, P = 0.013) and SMM
      index (SMI; from 6.24 +/- 1.07 to 6.91 +/- 1.54 kg/m2, P = 0.013), but not in
      handgrip strength (HS). Patients assigned to the multidisciplinary program (n =
      22) showed an improvement in both muscle mass [SMM (from 16.6 +/- 6.0 to 17.3 +/-
      5.7 Kg, P = 0.050) and SMI (from 6.63 +/- 1.65 to 6.91 +/- 1.52 kg/m2, P =
      0.038)] and functional status [HS (from 13.5 +/- 5.0 to 15.6 +/- 6.7; P = 0.028),
      gait speed (from 0.44 +/- 0.18 to 0.51 +/- 0.20, P = 0.047) and Short Physical
      Performance Battery (from 4.6 +/- 3.1 to 5.5 +/- 3.2, P = 0.047)] at 6 months.
      The effect was no longer present after discontinuation of the intervention and
      was restored after its re-introduction at 12 months. CONCLUSIONS: Nutritional and
      multidisciplinary interventions tailored on patient's functional status could be
      considered as strategies for the management of sarcopenia, a high prevalent
      condition in old adults living in long-term care institutions.

PMID- 29170985
TI  - Perceptions of busyness in the emergency department: an opportunity to address a
      training gap through competency based education.

PMID- 29170986
TI  - Medical students' intrinsic versus extrinsic motivation to engage in research as
      preparation for residency.

PMID- 29170987
TI  - From Girlhood to Motherhood: Rituals of Childbirth and Obstetrical Medicine Re
      Examined through John Milton.
AB  - This article considers how seventeenth-century writer John Milton engages in
      modes of thinking that register the obstetric revolution occurring during the
      period. During a time when physicians were gaining entry to the birthing room, a
      medical rhetoric of childbirth was developing that cast childbirth in new
      pathological terms. Milton's A Masque Presented at Ludlow Castle demonstrates how
      childbirth was influenced by emerging obstetrical language and practice, as well
      as the ways in which a writer might question such influence. Finally, this
      article also draws links between disrupted historical rituals of childbirth and
      modern anxieties about medically-centred birthing practices.

PMID- 29170988
TI  - Renaissance, reinvention, or rhetoric: mitochondria in reproductive medicine
      2017.

PMID- 29170989
TI  - Modeling energy intake and body weight effects of a long-acting amylin analogue.
AB  - The inhibitory effect of anti-obesity drugs on energy intake (EI) is counter
      acted by feedback regulation of the appetite control circuit leading to drug
      tolerance. This complicates the design and interpretation of EI studies in
      rodents that are used for anti-obesity drug development. Here, we investigated a
      synthetic long-acting analogue of the appetite-suppressing peptide hormone amylin
      (LAMY) in lean and diet-induced obese (DIO) rats. EI and body weight (BW) were
      measured daily and LAMY concentrations in plasma were assessed using defined time
      points following subcutaneous administration of the LAMY at different dosing
      regimens. Overall, 6 pharmacodynamic (PD) studies including a total of 173 rats
      were considered in this evaluation. Treatment caused a dose-dependent reduction
      in EI and BW, although multiple dosing indicated the development of tolerance
      over time. This behavior could be adequately described by a population model
      including homeostatic feedback of EI and a turnover model describing the
      relationship between EI and BW. The model was evaluated by testing its ability to
      predict BW loss in a toxicology study and was utilized to improve the
      understanding of dosing regimens for obesity therapy. As such, the model proved
      to be a valuable tool for the design and interpretation of rodent studies used in
      anti-obesity drug development.

PMID- 29170990
TI  - Lack of ethnic differences of moxifloxacin and metabolite pharmacokinetics in
      East Asian men.
AB  - This study was designed to investigate ethnic differences in the pharmacokinetics
      (PKs) of moxifloxacin and its metabolites, M1 (sulfo conjugate) and M2 (acyl
      glucuronate), among Japanese, Chinese, and Korean populations, following oral
      administration. We used a population PK modeling approach using data from a
      clinical study involving 79 healthy male volunteers. A comprehensive population
      PK model considering the PK mechanism of moxifloxacin and its metabolites was
      newly built. The structures of the final model were two-compartment for
      moxifloxacin and one-compartment for M1 and M2, with first-order absorption with
      lag time for all three compounds. The formation of M1 and M2 from moxifloxacin
      via a first-pass effect and subsequent metabolic clearance in the system were
      also modeled. Lean body mass on the central volume of distribution (V c ) and
      estimated glomerular filtration rate on renal clearance (CL r ) were identified
      as covariates of PKs of moxifloxacin. Additionally, bioavailability was slightly
      higher in Koreans, whereas CL r , non-renal clearance (CL nr ), and V c were
      slightly lower. Regarding M1 and M2, body surface area on CL r of M2 and UGT1A1*6
      on F of M2 were modeled. Korean ethnicity was observed to influence CL nr of M2,
      F of M2, and the metabolic clearance of moxifloxacin to M2. However, the exposure
      levels of moxifloxacin, M1, and M2 in Koreans were comparable to those in
      Japanese and Chinese because the effects of Korean ethnicity on some PK
      parameters were counterbalanced. These results suggest that PKs for moxifloxacin
      and its metabolites among East Asian populations are essentially similar.

PMID- 29170991
TI  - Facilitated enumeration of the silicate bacterium Paenibacillus mucilaginosus
      comb. nov. (formerly Bacillus mucilaginosus) via tetrazolium chloride
      incorporation into a double agar-based solid growth medium.
AB  - Accurate enumeration of Paenibacillus mucilaginosus (formerly Bacillus
      mucilaginosus) bacterium from environmental samples on solid medium is
      challenging owing to its extensive extracellular polysaccharides (EPS) excretion.
      In the present study, P. mucilaginosus enumeration has been facilitated by a
      simple modification: addition of triphenyl tetrazolium chloride (TTC) to growth
      medium and application of a second soft agar layer. Results show distinctively
      better and accurate colonies' count. This method can be applied to all bacterial
      species that produce excessive EPS that may interfere with direct count.

PMID- 29170992
TI  - Clinical strains of Lactobacillus reduce the filamentation of Candida albicans
      and protect Galleria mellonella against experimental candidiasis.
AB  - Candida albicans is the most common human fungal pathogen and can grow as yeast
      or filaments, depending on the environmental conditions. The filamentous form is
      of particular interest because it can play a direct role in adherence and
      pathogenicity. Therefore, the purpose of this study was to evaluate the effects
      of three clinical strains of Lactobacillus on C. albicans filamentation as well
      as their probiotic potential in pathogen-host interactions via an experimental
      candidiasis model study in Galleria mellonella. We used the reference strain
      Candida albicans ATCC 18804 and three clinical strains of Lactobacillus: L.
      rhamnosus strain 5.2, L. paracasei strain 20.3, and L. fermentum strain 20.4.
      First, the capacity of C. albicans to form hyphae was tested in vitro through
      association with the Lactobacillus strains. After that, we verified the ability
      of these strains to attenuate experimental candidiasis in a Galleria mellonella
      model through a survival curve assay. Regarding the filamentation assay, a
      significant reduction in hyphae formation of up to 57% was observed when C.
      albicans was incubated in the presence of the Lactobacillus strains, compared to
      a control group composed of only C. albicans. In addition, when the larvae were
      pretreated with Lactobacillus spp. prior to C. albicans infection, the survival
      rate of G. mellonela increased in all experimental groups. We concluded that
      Lactobacillus influences the growth and expression C. albicans virulence factors,
      which may interfere with the pathogenicity of these microorganisms.

PMID- 29170993
TI  - Limonoids from the roots of Trichilia sinensis and their cytotoxicities.
AB  - Six new compounds (1-4, 8, 10), along with six known limonoids (5-7, 9, 11, 12),
      were isolated from the roots of Trichilia sinensis. Their structures were
      elucidated on the basis of extensive spectroscopic methods including 1H NMR, 13C
      NMR, DEPT, HSQC, HMBC, 1H-1H COSY and ROESY experiments, as well as by comparison
      with the literature. All the compounds were evaluated for cytotoxicities against
      K562, SGC-7901 and BEL-7402 cell lines. Compounds 2, 7, 10, 11, and 12 showed
      weak inhibitory activity to the selected cell lines.

PMID- 29170994
TI  - "No go" donor hepatectomy in living-donor liver transplantation.
AB  - BACKGROUND: Selection of appropriate donors after rigorous evaluation is of
      paramount importance in living-donor liver transplantation. Despite this, donor
      surgery may not proceed due to unforeseen reasons. The aim of this paper is to
      study reasons for "no go" donor hepatectomy in living liver donors. PATIENTS AND
      METHODS: Donor operations stopped after surgical start, directly due to donor
      safety-related reasons, qualified for inclusion as "no go" donor hepatectomy.
      Living-donor evaluation was performed as per standard protocol. Data for
      consecutive living liver donors operated between April 2012 and November 2016
      were analyzed to evaluate reasons for "no go" donor hepatectomy in a liver
      transplantation unit at a tertiary care teaching hospital. RESULTS: In 307
      donors, the operation was aborted in 7 (2.3 %). One patient had unexpected
      biliary pathology with fibrosis found intraoperatively. Operations in five donors
      were abandoned in view of liver parenchymal abnormalities
      (fibrosis/steatohepatitis). One donor had hemodynamically significant bradycardia
      after handling the round ligament. All these donors recovered uneventfully and
      remained well on follow-up. CONCLUSIONS: "No go" donor hepatectomy remains a real
      possibility despite rigorous assessment. Although thresholds for on-table
      rejection of the donor after complete evaluation vary, "no go" hepatectomy is a
      calculated risk-avoidance approach.

PMID- 29170995
TI  - Correction to: Stepwise strategy for monitoring toxic cyanobacterial blooms in
      lentic water bodies.
AB  - Unfortunately, the name of the third author was incorrectly captured in the
      published online paper.

PMID- 29170996
TI  - Medicare hospital payment adjustments and nursing wages.
AB  - Despite the importance of the nursing profession for healthcare delivery, costs,
      and quality, there is relatively little research on how provider payments to
      hospitals affect the labor market for nurses. This study deals with the hospital
      wage index (HWI) adjustment to Medicare hospital payments, an area-level
      adjustment intended to compensate hospitals in high-cost labor markets. Since the
      HWI adjustment is based on hospital-reported labor costs, some argue that it
      incentivizes hospitals in concentrated markets to pay higher wages to nurses and
      other workers (the "circularity" critique). We investigate this critique using
      market-level data on the relative wages reported by nurses and hospital-level
      data on the average hourly wage for healthcare workers. For identification, we
      exploit a 2005 change in the geographic area used to define labor markets, which
      resulted in exogenous changes in the ability of some hospitals to influence their
      area's wage index. We find that worker-reported relative nurse wages and hospital
      reported healthcare worker wages are higher in some locations where hospitals
      experienced increased opportunities to game the circularity of the wage index,
      but these effects appear to be driven by pre-existing wage growth. Medicare's HWI
      adjustment method does not appear to suffer from inefficiency due to circularity.

PMID- 29170997
TI  - Differential Expression of Ion Channels in Adult and Neonatal Rat Ventral
      Respiratory Column.
AB  - In mammals, the neural control of breathing is attributed to circuits distributed
      along the ventral respiratory column (VRC) in the ventrolateral medulla. The VRC
      contains the kernel for generation of the inspiratory phase of respiratory rhythm
      and nuclei involved in central chemoreception. During development, the
      respiratory rhythm, as well as central chemosensitivity, adjusts to meet the
      changing physiological requirements associated with increased body weight and
      size. Gene expression in VRC ontogeny is well characterized. However, little is
      known about gene expression in the VRC during postnatal development. Here, we
      sought to characterize the changes in gene expression that occur in the VRC of
      the adult rat (5-6 months of age) in comparison with the VRC of neonate rat (1-4
      days old). We isolated total RNA from VRC tissue punches collected from thick
      transversal slices. We hybridized cDNA to a 5000-oligonucleotide rat microarray.
      We found that 218 genes (4.4%) of the 5000 genes in the microarray changed their
      expression in adult VRC with respect to that from neonate. To further analyze the
      modified expression of specific genes, we quantified the differential expression
      of 84 genes of neuronal ion channels using a quantitative RT-PCR array. This
      analysis confirmed the overexpression of 68 genes and the underexpression of 14
      genes in the VRC from adult compared with that from neonate. Our findings may
      help to explain the functional changes in respiratory rhythm and chemosensitivity
      occurring throughout life.

PMID- 29170999
TI  - The Baby Boom and later life: is critical care fit for the future?
AB  - Populations around the world are ageing while in many developed countries the
      proportion of elderly patients admitted to critical care is rising. It is clear
      that age alone should not be used as a reason for refusing intensive care
      admission. Critical care in this patient group is challenging in many ways: with
      advancing age, several physiological changes occur which all lead to a subsequent
      reduction of physical performance and compensatory capacity, in many cases
      additionally aggravated by chronic illness. Subsequently, these age-dependent
      changes (with or without chronic illness) increase the risk for death, treatment
      costs and a prolonged length of intensive care and hospital stay. This review
      explores the potential of using co-morbidity and frailty to predict outcome and
      to help to make better decisions about critical care admission in the elderly.
      The authors explore the challenges of using different frailty assessment tools
      and offer a model for holistic approach to answer these questions.

PMID- 29170998
TI  - Introducing TOPMAST, the first double-blind randomized clinical trial
      specifically dedicated to perioperative maintenance fluid therapy in adults.
AB  - BACKGROUND: Although prescribed to every patient undergoing surgery, maintenance
      fluid therapy is a poorly researched part of perioperative fluid therapy. The
      tonicity of the chosen solutions, could be an important cause of morbidity, with
      hyponatremia being a potential side effect of hypotonic solutions, where isotonic
      solution could lead to fluid overload. METHODS: The TOPMAST-trial is an ongoing
      prospective single-center double-blind randomized trial comparing an isotonic and
      a hypotonic maintenance fluid strategy during and after surgery in patients
      undergoing different types of major thoracic surgery. Patients receive NaCl 0.9%
      in glucose 5% with an added 40 mmol L-1 of potassium chloride or a premixed
      solution containing 54 mmol L-1 sodium, 55 mmol L-1 chloride and 26 mmol of
      potassium at a rate of 27 mL per kg of body weight per day. The primary
      hypothesis is that isotonic maintenance solutions cause a more positive
      perioperative fluid balance than hypotonic fluids. Different secondary safety
      endpoints will be explored, especially the effect of the study treatments on the
      occurrence electrolyte disturbances (e.g. hyponatremia, hyperchloremia) and a set
      of clinical endpoints. Efficacy endpoints include the need for resuscitation
      fluids and assessment of renal and hormonal adaptive mechanisms. An anticipated
      68 patients will be included between March 2017 and January 2018. DISCUSSION: The
      study will provide the most comprehensive evaluation of clinically important
      outcomes associated with the choice of perioperative maintenance fluid therapy.

PMID- 29171000
TI  - Applying pharmacokinetic/pharmacodynamic principles for optimizing antimicrobial
      therapy during continuous renal replacement therapy
AB  - Continuous renal replacement therapy (CRRT) is progressively supplanting
      intermittent haemodialysis (IHD) in critically ill patients. Although CRRT indeed
      offers more appropriate haemodynamic, fluid, and metabolic stability, concern is
      rising about its impact on concomitant drugs and, in particular, antimicrobial
      treatment. Antimicrobial dose recommendations have been elaborated to avoid drug
      accumulation and toxicity in patients undergoing IHD. However, these dosing
      regimens have resulted in significant underdosing in patients undergoing CRRT,
      thereby increasing the risk of treatment failure and development of resistance.
      Applying pharmacokinetic/pharmacodynamic (PK/PD) principles may aid one to obtain
      more adequate antimicrobial therapy during CRRT. Much progress has been made in
      recent years resulting in relevant changes in particular antimicrobial therapies.
      In this review, we discuss antimicrobials that are frequently used in an
      intensive care setting. Drugs are divided according to their PK/PD
      characteristics and, wherever possible, dose recommendations during CRRT are
      provided. Of course, while therapeutic drug monitoring remains the best way to
      cope with PK/PD variability within a critically ill CRRT population, its bedside
      use is actually limited to some specific antibiotics.

PMID- 29171001
TI  - Modern imaging techniques in intra-abdominal hypertension and abdominal
      compartment syndrome: a bench to bedside overview.
AB  - Intra-abdominal hypertension (IAH) is common in critically ill patients.
      Diagnosis is based on measurement of intraabdominal pressure, most commonly via
      the bladder. Modern imaging techniques with plain radiographs, computed
      tomography and magnetic resonance can help establish the diagnosis and also guide
      treatment. In 2013 the Abdominal Compartment Society (WSACS) published updated
      consensus definitions and recommendations for management of IAH and abdominal
      compartment syndrome (ACS). This review will give a concise overview of the
      important role radiographic imaging plays within these management guidelines.

PMID- 29171002
TI  - Pharmacokinetic/pharmacodynamic analysis of adjunctive perampanel in subjects
      with partial-onset seizures.
AB  - OBJECTIVES: Explore perampanel pharmacokinetics (PK) in all subjects (aged >=12
      years) vs adolescents (aged >=12 to <=17 years) with partial-onset seizures (POS)
      and identify factors explaining between-subject variability in efficacy using a
      population PK/pharmacodynamic (PD) analysis. MATERIALS & METHODS: Population PK
      analysis was performed using nonlinear mixed-effect modeling with data from phase
      II/III randomized, double-blind, placebo-controlled studies of adjunctive
      perampanel in POS. Perampanel exposure was predicted for all subjects and
      adolescents. Population PK/PD analyses were performed using data from phase III
      studies to explore the relationship between perampanel exposure and 28-day
      average seizure frequency and responder probability. RESULTS: Pooled perampanel
      PK data from 1318 subjects were described by a one-compartment disposition model.
      In the absence of antiepileptic drugs (AEDs) affecting perampanel PK, estimated
      perampanel apparent clearance (CL/F) was 0.668 L/h (all subjects) and 0.682 L/h
      (adolescent subjects). Co-administration of carbamazepine and
      oxcarbazepine/phenytoin reduced perampanel exposure. Gender, Asian race
      (excluding Japanese or Chinese), and increasing alanine aminotransferase lowered
      perampanel CL/F, but differences were small and not considered clinically
      relevant. Adolescent outcomes were similar to the total population. Based on
      PK/PD data from 1748 subjects, percent reduction in 28-day average seizure
      frequency from baseline and responder probability increased with increasing
      perampanel exposure; concomitant CYP3A-inducing AEDs lowered perampanel exposure
      but did not impact the slope for responder probability. CONCLUSIONS: These
      results are consistent with previous analyses but expand on these through
      inclusion of a larger number of patients from different ethnic groups, and
      demonstrate that outcomes were similar between adults and adolescents.

PMID- 29171004
TI  - The Evolution and Future of CAR T Cells for B-Cell Acute Lymphoblastic Leukemia.
AB  - Several CAR T designs with CD19 specificity have been associated with consistent
      responses in clinical trials with complete remission (CR) rates ranging from 70
      90%. Relevant challenges remain to be addressed, such as production time, early
      loss of CAR T cells, relapse due to loss of the target antigen, and prevention of
      severe cytokine release syndrome and neurotoxicity. This review describes
      constructs, clinical trial results, side effects, and future direction of CAR T
      cell therapy in B-ALL.

PMID- 29171003
TI  - Inhibition of monoacylglycerol lipase terminates diazepam-resistant status
      epilepticus in mice and its effects are potentiated by a ketogenic diet.
AB  - OBJECTIVE: Status epilepticus (SE) is a life-threatening and commonly drug
      refractory condition. Novel therapies are needed to rapidly terminate seizures to
      prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme
      responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2
      AG) and a major contributor to the brain pool of arachidonic acid (AA).
      Inhibiting of monoacylglycerol lipase modulates synaptic activity and
      neuroinflammation, 2 mediators of excessive neuronal activation underlying
      seizures. We studied the effect of a potent and selective irreversible MAGL
      inhibitor, CPD-4645, on SE that was refractory to diazepam, its neuropathologic
      sequelae, and the mechanism underlying the drug's effects. METHODS: Diazepam
      resistant SE was induced in adult mice fed with standard or ketogenic diet or in
      cannabinoid receptor type 1 (CB1) receptor knock-out mice. CPD-4645 (10 mg/kg,
      subcutaneously) or vehicle was dosed 1 and 7 h after status epilepticus onset in
      video-electroencephalography (EEG) recorded mice. At the end of SE, mice were
      examined in the novel object recognition test followed by neuronal cellloss
      analysis. RESULTS: CPD-4645 maximal plasma and brain concentrations were attained
      0.5 h postinjection (half-life = 3.7 h) and elevated brain 2-AG levels by
      approximately 4-fold. CPD-4645 administered to standard diet-fed mice
      progressively reduced spike frequency during 3 h postinjection, thereby
      shortening SE duration by 47%. The drug immediately abrogated SE in ketogenic
      diet-fed mice. CPD-4645 rescued neuronal cell loss and cognitive deficit and
      reduced interleukin (IL)-1beta and cyclooxygenase 2 (COX-2) brain expression
      resulting from SE. The CPD-4645 effect on SE was similar in mice lacking CB1
      receptors. SIGNIFICANCE: MAGL represents a novel therapeutic target for treating
      status epilepticus and improving its sequelae. CPD-4645 therapeutic effects
      appear to be predominantly mediated by modulation of neuroinflammation.

PMID- 29171005
TI  - Is There a Downside to Anticipating the Upside? Children's and Adults' Reasoning
      About How Prior Expectations Shape Future Emotions.
AB  - Four- to 10-year-olds and adults (N = 205) responded to vignettes involving three
      individuals with different expectations (high, low, and no) for a future event.
      Participants judged characters' pre-outcome emotions, as well as predicted and
      explained their feelings following three events (positive, attenuated, and
      negative). Although adults rated high-expectation characters more negatively than
      low-expectation characters after all outcomes, children shared this intuition
      starting at 6-7 years for negative outcomes, 8-10 years for attenuated, and never
      for positive. Comparison to baseline (no expectation) indicated that
      understanding the costs of high expectations emerges first and remains more
      robust across age than recognition that low expectations carry benefits.
      Explanation analyses further clarified this developing awareness about the
      relation between thoughts and emotions over time.

PMID- 29171007
TI  - High-Ability Grouping: Benefits for Gifted Students' Achievement Development
      Without Costs in Academic Self-Concept.
AB  - Effects of full-time ability grouping on students' academic self-concept (ASC)
      and mathematics achievement were investigated in the first 3 years of secondary
      school (four waves of measurement; students' average age at first wave: 10.5
      years). Students were primarily from middle and upper class families living in
      southern Germany. The study sample comprised 148 (60% male) students from 14
      gifted classes and 148 (57% male) students from 25 regular classes (matched by
      propensity score matching). Data analyses involved multilevel and latent growth
      curve analyses. Findings revealed no evidence for contrast effects of class
      average achievement or assimilation effects of class type on students' ASC. ASC
      remained stable over time. Students in gifted classes showed higher achievement
      gains than students in regular classes.

PMID- 29171006
TI  - BAD knockout provides metabolic seizure resistance in a genetic model of epilepsy
      with sudden unexplained death in epilepsy.
AB  - Metabolic alteration, either through the ketogenic diet (KD) or by genetic
      alteration of the BAD protein, can produce seizure protection in acute
      chemoconvulsant models of epilepsy. To assess the seizure-protective role of
      knocking out (KO) the Bad gene in a chronic epilepsy model, we used the Kcna1-/-
      model of epilepsy, which displays progressively increased seizure severity and
      recapitulates the early death seen in sudden unexplained death in epilepsy
      (SUDEP). Beginning on postnatal day 24 (P24), we continuously video monitored
      Kcna1-/- and Kcna1-/- Bad-/- double knockout mice to assess survival and seizure
      severity. We found that Kcna1-/- Bad-/- mice outlived Kcna1-/- mice by
      approximately 2 weeks. Kcna1-/- Bad-/- mice also spent significantly less time in
      seizure than Kcna1-/- mice on P24 and the day of death, showing that BadKO
      provides seizure resistance in a genetic model of chronic epilepsy.

PMID- 29171008
TI  - Patient-reported outcome measures for young people with developmental
      disabilities: incorporation of design features to reduce cognitive demands.
AB  - : Use of patient-reported outcome measures (PROMs) may increase the involvement
      of young people with developmental disabilities in their healthcare decisions and
      healthcare-related research. Young people with developmental disabilities may
      have difficulty completing PROMs because of extraneous assessment demands that
      require additional cognitive processes. However, PROM design features may
      mitigate the impact of these demands. We identified and evaluated six pediatric
      PROMs of self-care and domestic life tasks for the incorporation of suggested
      design features that can reduce cognitive demands. PROMs incorporated an average
      of 6 out of 11 content, 7 out of 14 layout, and 2 out of 9 administration
      features. This critical review identified two primary gaps in PROM design: (1)
      examples and visuals were not optimized to reduce cognitive demands; and (2)
      administration features that support young people's motivation and self-efficacy
      and reduce frustration were underutilized. Because assessment demands impact the
      validity of PROMs, clinicians should prospectively consider the impact of these
      demands when selecting PROMs and interpreting scores. WHAT THIS PAPER ADDS:
      Patient-reported outcome measure (PROM) design features can reduce assessment
      demands related to cognitive processes. Pediatric PROMs underutilize design
      features that decrease cognitive demands of self-reporting.

PMID- 29171009
TI  - Bevacizumab in combination with different platinum-based doublets in the first
      line treatment for advanced nonsquamous non-small-cell lung cancer: A network
      meta-analysis.
AB  - Platinum-based doublet chemotherapy with or without bevacizumab is the standard
      treatment for untreated advanced nonsquamous non-small-cell lung cancer (NS
      NSCLC). However, adding bevacizumab to chemotherapies other than paclitaxel
      carboplatin is, though widely applied clinically, largely unjustified due to the
      lack of head-to-head data. We performed a Bayesian network meta-analysis (NMA) to
      address this important issue. Data of 8,548 patients from 18 randomized
      controlled trials (RCTs) receiving six treatments, including taxane-platinum
      (Taxane-Pt), gemcitabine-platinum (Gem-Pt), pemetrexed-platinum (Pem-Pt), taxane
      platinum + bevacizumab (Taxane-Pt + B), gemcitabine-platinum + bevacizumab (Gem
      Pt + B) and pemetrexed-platinum + bevacizumab (Pem-Pt + B), were incorporated
      into the analyses. Direct and indirect evidence of overall survival (OS) and
      progression-free survival (PFS) were synthesized at the hazard ratio (HR) scale
      and evidence of objective response rate (ORR) and serious adverse events (SAE)
      were synthesized at the odds ratio (OR) scale. Taxane-Pt + B showed significant
      advantages in OS (HR = 0.79, p < 0.001), PFS (HR = 0.54, p < 0.001) and ORR (OR =
      2.7, p < 0.001) over Taxane-Pt with comparable tolerability (OR = 3.1, p = 0.08).
      Gem-Pt + B showed no OS benefit compared to any other treatment. No significant
      differences were detected between Pem-Pt + B and Pem-Pt in four outcomes. In
      terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt + B were ranked the first
      and second, respectively. In conclusion, in the first-line treatment for advanced
      NS-NSCLC, Taxane-Pt and Gem-Pt are the most and least preferable regimens to be
      used with bevacizumab, respectively. Adding bevacizumab to Pem-Pt remains
      unjustified because it fails to improve efficacy or tolerability. In terms of the
      benefit-risk ratio, Pem-Pt and Taxane-Pt + B are the best and second-best
      treatment for this population.

PMID- 29171010
TI  - Prenatal exposure to ketamine in rats: Implications on animal models of
      schizophrenia.
AB  - Schizophrenia is a complex neuropsychiatric disorder characterized by
      hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The
      aim of this study was to propose a prenatal treatment with ketamine, a
      psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA
      receptors, as a neurodevelopmental animal model of schizophrenia. The drug was
      applied (i.m. 60 mg.kg-1  h-1 ) in pregnant Sprague-Dawley rats on gestational
      Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10
      weeks old) stages. Also, hippocampal CA1-CA3 morphology was assessed in adult
      animals through a Nissl stain. Results showed a disinhibition and hyperactive
      behavior in pubertal animals exposed to ketamine, followed in adulthood with
      cognitive impairments, social withdrawal, anxiety, depression, and aggressive
      like behaviors. In the hippocampus, a reduction of the CA3 layer thickness was
      observed, without changes in cell density. These results strongly suggest a
      robust link between prenatal pharmacologic manipulation of NMDA receptors and
      schizophrenia.

PMID- 29171011
TI  - Stroke-like migraine attacks after radiation therapy: A misnomer?
AB  - OBJECTIVE: To understand the frequency of electrographic and clinical seizures in
      patients with stroke-like migraine attacks after radiation therapy (SMART), and
      determine whether SMART warrants comprehensive electroencephalographic (EEG)
      monitoring and aggressive seizure management. METHODS: We searched our magnetic
      resonance brain imaging report database for all patients between January 2013 and
      December 2015 for suspected SMART syndrome. Clinical inclusion criteria were
      further applied as follows: inpatient adults (>18 years of age) with history of
      cranial radiation presenting with acute neurologic deficits as primary admission
      reason who lacked evidence of recurrent or new brain malignancy, stroke, or
      infectious agents in cerebrospinal fluid. Six patients were identified. All 6
      patients underwent prolonged video EEG monitoring as part of our standard
      protocol. RESULTS: All patients but 1 were found to have multiple or prolonged
      electrographic seizures consistent with status epilepticus during video EEG
      monitoring. Their neurological deficit and/or mental status change improved in
      parallel with resolution of the seizure activity. SIGNIFICANCE: SMART is likely a
      misnomer that underestimates the significance of seizures and status epilepticus
      in the pathophysiology and clinical presentation of the syndrome. Systematic
      continuous EEG monitoring and appropriate seizure management is warranted to
      reduce symptom duration and optimize clinical outcome.

PMID- 29171012
TI  - Children's anxiety symptoms and salivary immunoglobulin A: A mutual regulatory
      system?
AB  - Anxiety can impact the immune system resulting in negative health outcomes.
      Salivary immunoglobulin A (sIgA) is a first line of defense against foreign
      antigens, with lowered levels indicative of weakened mucosal immunity. Little is
      known about how anxiety symptoms affect the diurnal rhythm of sIgA secretion, or
      the longitudinal transactional sequence between the two in children and
      adolescents. The goals of the two studies were to: (i) explore the concurrent
      associations between self-reported anxiety symptoms and diurnal variations of
      sIgA across the day using repeated daily samples of sIgA; and (ii) examine
      transactional relations between children's anxiety and aggregated total amount of
      sIgA levels across successive periods from middle childhood (Wave 1; ages 9-12)
      to early adolescence (Wave 2; ages 12-15), and from early to mid- adolescence
      (Wave 3; ages 15-18). Concurrent results showed a steeper (positive) rise in
      diurnal slope of sIgA from awakening to 5 hr post-awakening in children with
      higher anxiety. Longitudinally, higher levels of total anxiety, and specifically,
      worries at Wave 1 significantly predicted lower cumulative daily levels of sIgA 3
      years later at Wave 2. Lowered sIgA levels at Wave 2 in turn predicted higher
      anxiety at Wave 3, illustrating a "vicious cycle" feedback loop. These findings
      broaden our understanding of the developmental links between anxiety symptoms,
      the immune system, and health.

PMID- 29171013
TI  - Severe infantile onset developmental and epileptic encephalopathy caused by
      mutations in autophagy gene WDR45.
AB  - Heterozygous de novo variants in the autophagy gene, WDR45, are found in beta
      propeller protein-associated neurodegeneration (BPAN). BPAN is characterized by
      adolescent onset dementia and dystonia; 66% patients have seizures. We asked
      whether WDR45 was associated with developmental and epileptic encephalopathy
      (DEE). We performed next generation sequencing of WDR45 in 655 patients with
      developmental and epileptic encephalopathies. We identified 3/655 patients with
      DEE plus 4 additional patients with de novo WDR45 pathogenic variants (6
      truncations, 1 missense); all were female. Six presented with DEE and 1 with
      early onset focal seizures and profound regression. Median seizure onset was 12
      months, 6 had multiple seizure types, and 5/7 had focal seizures. Three patients
      had magnetic resonance susceptibility-weighted imaging; blooming was noted in the
      globus pallidi and substantia nigra in the 2 older children aged 4 and 9 years,
      consistent with iron accumulation. We show that de novo pathogenic variants are
      associated with a range of developmental and epileptic encephalopathies with
      profound developmental consequences.

PMID- 29171015
TI  - Dental health-care service utilisation and its determinants in West Iran: a cross
      sectional study.
AB  - BACKGROUND: Dental health care is not only an effective strategy for the
      prevention, early diagnosis and treatment of oral diseases but also contributes
      to the general health of communities. This study aimed to investigate the
      situation of dental health-care service utilisation and its determinants in
      Kermanshah city, western Iran, in 2015. METHODS AND MATERIALS: A cross-sectional
      study on a total of 894 household heads was conducted. The participants were
      selected using a multistage sampling technique. A self-administered questionnaire
      was used to collect the data. Multiple logistic regression was performed to
      assess factors associated with utilisation of dental-care services and a negative
      binomial regression was carried out to identify the main factor associated with
      the frequency of visiting a dentist for dental health care. A statistically
      significant association was considered at a value of P < 0.05. All the analyses
      were performed using STATA version 12. FINDING: Of the total household heads who
      participated in the study, 60.3% and 9.9% reported visiting a dentist for dental
      treatment in the past year and for 6-monthly dental check-ups, respectively. The
      average +/- standard deviation number of visits by a respondent was 2.08 +/-
      2.97. Of the total number of respondents, 281 (31.4%) reported visiting a dentist
      once or twice in the last 12 months for dental health-care services, while 28.9%
      reported visiting a dentist more than twice in the same time period. Ageing,
      having dental insurance, higher income, being a university graduate, self-rated
      poor oral health and not regularly brushing own teeth were the main factors
      associated with utilisation of dental health-care services. CONCLUSION: Our study
      indicates that dental health-care utilisation among households in the study area
      was influenced by a number of factors, including being socio-economically
      disadvantaged, self-rated poor oral health and not regularly brushing own teeth.
      Therefore, in this setting, dental-intervention programmes, including dental
      health insurance, should focus on mechanisms that can strengthen utilisation of
      preventive dental health-care services among disadvantaged households.

PMID- 29171014
TI  - The Influence of Big (Clinical) Data and Genomics on Precision Medicine and Drug
      Development.
AB  - Drug development continues to be costly and slow, with medications failing due to
      lack of efficacy or presence of toxicity. The promise of pharmacogenomic
      discovery includes tailoring therapeutics based on an individual's genetic
      makeup, rational drug development, and repurposing medications. Rapid growth of
      large research cohorts, linked to electronic health record (EHR) data, fuels
      discovery of new genetic variants predicting drug action, supports Mendelian
      randomization experiments to show drug efficacy, and suggests new indications for
      existing medications. New biomedical informatics and machine-learning approaches
      advance the ability to interpret clinical information, enabling identification of
      complex phenotypes and subpopulations of patients. We review the recent history
      of use of "big data" from EHR-based cohorts and biobanks supporting these
      activities. Future studies using EHR data, other information sources, and new
      methods will promote a foundation for discovery to more rapidly advance precision
      medicine.

PMID- 29171016
TI  - Long-term development of gait after multilevel surgery in children with cerebral
      palsy: a multicentre cohort study.
AB  - AIM: We investigated the long-term efficacy and safety of multilevel surgery
      (MLS) in ambulatory children with bilateral spastic cerebral palsy (CP). METHOD:
      Two hundred and thirty-one children were evaluated at short term (1.1y, SD 0.4)
      and long term (9.1y, SD 3.0) follow-up using clinical examination and gait
      analysis. MLS was investigated by studying changes in the Gait Profile Score
      (GPS) referenced to the minimally important clinical difference. RESULTS:
      Ambulatory children aged 10 years and 7 months (SD 2y 11mo) at MLS in Gross Motor
      Function Classification System levels I (19), II (144), and III (68) showed a
      decrease (improvement) in preoperative GPS from 16.3 degrees  (SD 4.8) to 11.3
      degrees  (SD 3.2) at short-term follow-up, an improvement of 5 degrees . At long
      term follow-up, GPS was maintained at 11.4 degrees  (SD 3.1). Overall, 177
      (76.6%) children maintained their improvement in GPS after 9 years.
      INTERPRETATION: Multilevel surgery is a safe and effective surgical intervention,
      which leads to a significant improvement in gait kinematics in children with
      bilateral spastic CP. This study improves our understanding of MLS in the long
      term and will help to inform families and children when planning for MLS. WHAT
      THIS PAPER ADDS: Largest study of multilevel surgery (MLS) for children with
      bilateral spastic cerebral palsy, with longest follow-up. MLS resulted in
      significant long-term improvements in gait function. Minor adverse events were
      common, while events requiring intervention were uncommon (4% of children).
      Thirty-nine per cent of children required additional surgery during follow-up.
      'Single-event multilevel surgery' was changed to the more realistic term
      'multilevel surgery'.

PMID- 29171017
TI  - Pathogenesis and therapeutic targeting of aberrant MYC expression in
      haematological cancers.
AB  - Identifying and therapeutically targeting cancer cell liabilities is of utmost
      importance in order to improve the treatment of patients with malignancies of
      poor prognosis. The MYC family genes (MYC, MYCN and MYCL) are among the most
      deregulated proto-oncogenes in human cancer. Aberrant MYC expression is
      frequently associated with poor prognosis. Although many aspects of MYC-mediated
      tumour biology are well characterized, there are currently no effective means for
      targeting MYC in a specific manner that have been established for clinical use.
      This review first discusses the role of MYC in the pathogenesis of haematopoietic
      malignancies, and secondly summarizes how insight into MYC functions could be
      translated into therapeutic approaches. In particular, we will address the
      possibilities of taking advantage of MYC-induced cancer cell vulnerabilities that
      could be exploited in terms of synthetic lethal interactions.

PMID- 29171018
TI  - Personal history of non-melanoma skin cancer diagnosis and death from melanoma in
      women.
AB  - Melanoma incidence is increasing. We evaluated risk of melanoma death after
      diagnosis of non-melanoma skin cancer (NMSC). We followed 77,288 female American
      nurses from the Nurses' Health Study from 1986 to 2012. We used Cox proportional
      hazards models to determine the hazard ratio (HR) of lethal and non-lethal
      melanoma diagnosis and melanoma death, according to personal NMSC history. Among
      melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of
      melanoma with a Breslow thickness >=0.8 mm or Clark's levels of IV and V
      according to history of NMSC. We documented 930 melanoma cases without NMSC
      history and 615 melanoma cases with NMSC history over 1.8 million person-years.
      The multivariate-adjusted HR (95% confidence interval) of melanoma death
      associated with personal history of NMSC was 2.89 (1.85-4.50). Women with history
      of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR
      (95% CI): 2.31 (2.05-2.60) vs. 1.74 (1.05-2.87)). Among melanoma cases, women
      with history of NMSC had a non-significant decreased risk of melanoma deaths
      (0.87 (0.55-1.37)), Breslow thickness >=0.8 mm (0.85 (0.59-1.21)) and Clark's
      levels IV and V (0.81(0.52-1.24)). Women with NMSC history were less likely to be
      diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of
      melanoma diagnosis was increased in both subtypes, leading to the increased risk
      of melanoma death. Our findings suggest the continued need for dermatologic
      screening for patients after NMSC diagnosis, given increased melanoma risk. Early
      detection among NMSC patients may decrease deaths from melanoma.

PMID- 29171019
TI  - Cortisol profiles differentiated in adolescents and young adult males with
      fragile X syndrome versus autism spectrum disorder.
AB  - BACKGROUND: Fragile X syndrome (FXS) and non-syndromic autism spectrum disorder
      (ASD) are distinct disorders with overlapping behavioral features. Both disorders
      are also highly associated with anxiety with abnormal physiological regulation
      implied mechanistically. Some reports suggest atypical hypothalamus-pituitary
      adrenal (HPA) axis function, indexed via aberrant cortisol reactivity, in both
      FXS and non-syndromic ASD. However, no study has compared cortisol reactivity
      across these two disorders, or its relationship to ASD symptom severity. METHODS:
      Cortisol reactivity (prior to and following a day of assessments) was measured in
      54 adolescent/young adult males with FXS contrasted to 15 males with non
      syndromic ASD who had low cognitive abilities. RESULTS: Greater ASD symptom
      severity was related to increased cortisol reactivity and higher levels at the
      end of the day, but only in the non-syndromic ASD group. Elevated anxiety was
      associated with increased HPA activation in the group with FXS alone.
      CONCLUSIONS: Taken together, findings suggest a unique neuroendocrine profile
      that distinguishes adolescent/young adult males with FXS from those with non
      syndromic ASD. Severity of ASD symptoms appears to be related to cortisol
      reactivity in the non-syndromic ASD sample, but not in FXS; while anxiety
      symptoms are associated with HPA activation in the FXS sample, but not in ASD
      despite a high prevalence of ASD, anxiety and physiological dysregulation
      characteristic in both populations.

PMID- 29171022
TI  - Screening for ASXL1 and SRSF2 mutations is imperative for treatment decision
      making in otherwise low or intermediate-1 risk patients with myelofibrosis.

PMID- 29171020
TI  - Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated
      Metabolism of Montelukast in Humans.
AB  - The oxidation of montelukast is mainly mediated by cytochrome P450 (CYP) 2C8, but
      other mechanisms may contribute to its disposition. In healthy volunteers, we
      investigated the effects of two widely used P2Y12 inhibitors on montelukast
      pharmacokinetics. Clopidogrel (300 mg on day 1 and 75 mg on day 2) increased the
      area under the plasma concentration-time curve (AUC) of montelukast 2.0-fold (90%
      confidence interval (CI) 1.72-2.28, P < 0.001) and decreased the M6:montelukast
      AUC0-7h ratio to 45% of control (90% CI 40-50%, P < 0.001). Prasugrel (60 mg on
      day 1 and 10 mg on day 2) had no clinically meaningful effect on montelukast
      pharmacokinetics. Our results imply that clopidogrel is at least a moderate
      inhibitor of CYP2C8, but prasugrel is not a clinically relevant CYP2C8 inhibitor.
      The different interaction potentials of clopidogrel and prasugrel are important
      to consider when antiplatelet therapy is planned for patients at risk for
      polypharmacy with CYP2C8 substrates.

PMID- 29171023
TI  - Thinking fast and slow - in clinical psychiatry.

PMID- 29171021
TI  - Xenopus-derived glucagon-like peptide-1 and polyethylene-glycosylated glucagon
      like peptide-1 receptor agonists: long-acting hypoglycaemic and insulinotropic
      activities with potential therapeutic utilities.
AB  - BACKGROUND AND PURPOSE: Incretin-based therapies based on glucagon-like peptide-1
      (GLP-1) receptor agonists are effective treatments of type 2 diabetes. Abundant
      research has focused on the development of long-acting GLP-1 receptor agonists.
      However, all GLP-1 receptor agonists in clinical use or development are based on
      human or Gila GLP-1. We have identified a potent GLP-1 receptor agonist, xGLP-1B,
      based on Xenopus GLP-1. EXPERIMENTAL APPROACH: To further modify the structure of
      xGLP-1B, alanine scanning was performed to study the structure -activity
      relationship of xGLP-1B. Two strategies were then employed to improve
      bioactivity. First, the C-terminal tail of lixisenatide was appended to cysteine
      altered xGLP-1B analogues. Second, polyethylene glycol (PEG) chains with
      different molecular weights were conjugated with the peptides, giving a series of
      PEGylated conjugates. Comprehensive bioactivity studies of these conjugates were
      performed in vitro and in vivo. RESULTS: From the in vitro receptor activation
      potency and in vivo acute hypoglycaemic activities of conjugates 25 -36, 33 was
      identified as the best candidate for further biological assessments. Conjugate 33
      exhibited prominent hypoglycaemic and insulinotropic activities, as well as
      improved pharmacokinetic profiles in vivo. The prolonged antidiabetic duration of
      33 was further confirmed by pre-oral glucose tolerance tests (OGTT) and multiple
      OGTT. Furthermore, chronic treatment of db/db mice with 33 ameliorated non
      fasting blood glucose and insulin levels, reduced HbA1c values and normalized
      their impaired glucose tolerance. Importantly, no in vivo toxicity was observed
      in mice treated with 33. CONCLUSIONS AND IMPLICATIONS: Peptide 33 is a promising
      long-acting type 2 diabetes therapeutic deserving further investigation.

PMID- 29171024
TI  - miR-19b-3p induces cell proliferation and reduces heterochromatin-mediated
      senescence through PLZF in goat male germline stem cells.
AB  - Promyelocytic leukemia zinc finger PLZF, known as ZBTB16 or ZFP145 is a critical
      zinc finger protein of male germline stem cells (mGSCs), it's an essential
      transcriptional factor for goat testis development and spermatogenesis. Loss of
      PLZF results in progressive depletion of SSCs after the first wave of
      spermatogenesis leading to eventual spermatogenic arrest, apparently the result
      of a shift in the balance in SSC fate away from self-renewal and toward
      differentiation. Cumulating evidences have demonstrated that microRNAs are
      expressed in a cell-specific or stage-specific manner during spermatogenesis and
      acts as regulators on specific makers such as Stra8, ETV5, and PLZF. However, the
      post transcriptional function of PLZF still poorly elucidate in mGSCs.
      Bioinformatic analysis and dual luciferase reporter assay showed that miR-19b-3p
      binds the 3'UTR of PLZF, suggesting that PLZF is a direct target of miR-19b-3p.
      The profile of miR-19b-3p and PLZF analyzed in dairy goat testis at different age
      showed that miR-19b-3p was significantly up-regulated in goat testis at 1, 3, 6
      months and downregulated at 12, 18, and 24 months which was inversely correlated
      with PLZF in the same testis. Focusing on the role of miR-19b-3p, we found that
      miR-19b-3p changes c-KIT and mTOR signaling through PLZF to promote proliferation
      in goat nGSCs and infertile mice testes. Over-expression of PLZF significantly
      reversed miR-19b-3p-mediated proliferation in mice testes. We found also that miR
      19b-3p reduced heterochromatin-mediated senescence through PLZF localized on
      HP1alpha. Taken together, our findings indicate that miR-19b-3p promotes
      proliferation and reduces heterochromatin-mediated senescence through PLZF in
      mGSCs.

PMID- 29171025
TI  - 25-Hydroxy vitamin D3 serum concentration in dogs with acute polyradiculoneuritis
      compared to matched controls.
AB  - OBJECTIVES: To determine if dogs with acute polyradiculoneuritis have lower serum
      25-hydroxy vitamin D3 concentration compared to a control group of dogs with
      idiopathic epilepsy. MATERIALS AND METHODS: Retrospective case-control study of
      21 dogs with acute canine polyradiculoneuritis and 21 control dogs with
      idiopathic epilepsy matched for year and season of presentation from a referral
      hospital population in the UK. Serum concentration of 25-hydroxy vitamin D3 was
      compared between groups using Student's t-test. RESULTS: Dogs with acute canine
      polyradiculoneuritis had significantly lower (P=0.033) serum 25-hydroxy vitamin
      D3 concentration (87.1 nmol/L +/-55.4 nmol/L) compared to a control group with
      idiopathic epilepsy (113 nmol/L +/-66.3 nmol/L). CLINICAL SIGNIFICANCE: The cause
      and clinical significance of the altered vitamin D status in dogs with acute
      polyradiculoneuritis are not clear and require further investigation. Our
      findings pave the way for improved understanding of acute canine
      polyradiculoneuritis and, potentially, improved clinical management, if a causal
      role for 25-hydroxy vitamin D3 is defined.

PMID- 29171026
TI  - Hepatocellular carcinoma in two captive golden-headed lion tamarins
      (Leontopithecus chrysomelas).
AB  - Two cases of hepatocellular carcinoma (HCC) in 2 female captive golden-headed
      lion tamarins (Leontopithecus chrysomelas) are described. HCC was diagnosed in
      both, with pulmonary metastasis in one of them. Neoplastic cells were positive
      for hepatocyte-specific antigen (HSA) by immunohistochemistry, confirming the
      diagnosis.

PMID- 29171027
TI  - On the Validity of Beer-Lambert Law and its Significance for Sunscreens.
AB  - The sun protection factor (SPF) is the most important quantity to characterize
      the performance of sunscreens. As the standard method for its determination is
      based on clinical trials involving irradiation of human volunteers, calculations
      of sunscreen performance have become quite popular to reduce the number of in
      vivo studies. Such simulations imply the calculation of UV transmittance of the
      sunscreen film using the amounts and spectroscopic properties of the UV absorbers
      employed, and presuppose the validity of the Beer-Lambert law. As sunscreen films
      on human skin can contain considerable concentrations of UV absorbers, it is
      questioned whether the Beer-Lambert law is still valid for these systems. The
      results of this work show that the validity of the Beer-Lambert law is still
      given at the high concentrations at which UV absorbers occur in sunscreen films
      on human skin.

PMID- 29171028
TI  - The mechanosensitive Piezo1 channel: structural features and molecular bases
      underlying its ion permeation and mechanotransduction.
AB  - The evolutionarily conserved Piezo family of proteins, including Piezo1 and
      Piezo2, encodes the long-sought-after mammalian mechanosensitive cation channels
      that play critical roles in various mechanotransduction processes such as touch,
      pain, proprioception, vascular development and blood pressure regulation.
      Mammalian Piezo proteins contain over 2500 amino acids with numerous predicted
      transmembrane segments, and do not bear sequence homology with any known class of
      ion channels. Thus, it is imperative, but challenging, to understand how they
      serve as effective mechanotransducers for converting mechanical force into
      electrochemical signals. Here, we review the recent major breakthroughs in
      determining the three-bladed, propeller-shaped structure of mouse Piezo1 using
      the state-of-the-art cryo-electron microscopy (cryo-EM) and functionally
      dissecting out the molecular bases that define its ion permeation and
      mechanotransduction properties, which provide key insights into clarifying its
      oligomeric status and pore-forming region. We also discuss the hypothesis that
      the complex Piezo proteins can be deduced into discrete mechanotransduction and
      ion-conducting pore modules, which coordinate to fulfil their specialized
      function in mechanical sensing and transduction, ion permeation and selection.

PMID- 29171029
TI  - Stress degradation of edaravone: Separation, isolation and characterization of
      major degradation products.
AB  - In the present study the International Conference on Harmonization-prescribed
      stress degradation was carried out to study the degradation profile of edaravone.
      To establish a Quality by Design (QbD)-assisted stability-indicating assay, the
      reaction solutions in which different degradation products were formed were
      mixed. Plackett Burman and central composite design were used to screen and
      optimize experimental variables to resolve edaravone and its impurities with good
      peak symmetry using an RP C18 column. The method was validated according to
      International Conference on Harmonization guidelines. Seven unknown and two known
      degradation products were identified and characterized by LC-MS/MS. Two major
      degradation products formed under thermal degradation were isolated and
      characterized as 4-(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl-4-(4,5
      dihydro-5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-methyl-1-phenyl-1H-pyrazol
      5(4H)-one and 3-hydroxy-dihydro-thiazolo[1-(2-methyl-buta-1,3dienyl)-1
      phenylhydrazine]5-one. The degradation pathways of degradants were proposed based
      on m/z values.

PMID- 29171030
TI  - A separable quadratic surrogate total variation minimization algorithm for
      accelerating accurate CT reconstruction from few-views and limited-angle data.
AB  - PURPOSE: Total variation minimization (TVM) is a popular and useful method for
      accurate CT reconstruction from few-views and limited-angle data. However, the
      optimization procedure of previous TVM-based algorithms is very time-consuming.
      The purpose of this paper was to accelerate the high image quality CT
      reconstruction from few-views and limited-angle data. METHOD: A new optimization
      algorithm based on the optimization transfer principle is proposed. The proposed
      algorithm uses TVM as the regularization term of the cost function that ensures
      the quality of the CT image reconstructed from few-views and limited-angle data.
      Additionally, half of the square of the difference between the original
      projection and the forward projection is used as the fidelity term. We then
      proved that the regularization term, i.e., 2-norm TV, is a convex function. Based
      on the convexity of the regularization and fidelity terms, a separable quadratic
      surrogate (SQS) function was proposed to substitute the regularization and
      fidelity terms. The solution of the cost function can be obtained by minimizing
      the SQS function and building the next SQS function at the minimum point.
      RESULTS: Both numerical simulations and simulations using real experimental data
      showed that the proposed algorithm reconstruct high-quality CT image from few
      views and limited-angle data. The differences between the image reconstructed by
      the proposed algorithm and the images reconstructed by the previous algorithms
      are very small. However, the proposed algorithm required less than 1/10 time of
      the computational time of the previous algorithms. The image quality is not
      assessed in a rigorous way. CONCLUSION: The proposed algorithm can greatly
      accelerate the accurate CT reconstruction from few-views and limited-angle data
      relative to previous algorithms.

PMID- 29171031
TI  - Comparison of hybrid and cross fragmentation patterns in terms of phaco time and
      corneal effects.
AB  - PURPOSE: To compare two different fragmentation patterns in femtosecond laser
      assisted cataract surgery (FLACS) in terms of phaco values, postoperative
      endothelial cell count (ECC) and corneal thickness (CT). METHODS: This non
      randomized, retrospective cross-sectional study included patients with senile
      cataract of grade 3 who underwent FLACS using the LenSx laser system. In Group 1
      (32 eyes), lens fragmentation was created as a cross pattern. In Group 2 (35
      eyes), lens fragmentation was created as a hybrid pattern. Intraoperative
      measurements were of the femtosecond procedure time, the ultrasound (US) total
      time, effective phacoemulsification time (EPT) and mean phacoemulsification power
      (MPP). Postoperative measurements were of CT and ECC at day 1, day 7 and 4 weeks
      after surgery. RESULTS: MPP and the US total time were significantly less with
      the hybrid pattern (P < 0.001, and P = 0.003). The EPT did not differ between the
      two groups (P = 0.266). The CT increased significantly in Group 1 from pre
      operative to first day after surgery (28.1 +/- 14.9 in Group 1, and 9.8 +/- 15.3
      in Group 2) (P < 0.001). The loss in ECC as a percentage was significantly
      greater in Group 1, 1 day, 1 week and 1 month after surgery (P = 0.18, 0.49 and
      0.07, respectively). CONCLUSION: The hybrid fragmentation method resulted in less
      time spent with the phaco being on and with less phaco power. It also caused less
      loss in ECC and milder changes in CT during the early post-operative time. 50:319
      323, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29171032
TI  - Immunological differences between insect venom-allergic patients with and without
      immunotherapy and asymptomatically sensitized subjects.
AB  - BACKGROUND: Currently available tests are unable to distinguish between
      asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A
      reliable serological marker to monitor venom immunotherapy (VIT) does also not
      exist. Our aim was to find reliable serological markers to predict tolerance to
      bee and vespid stings. METHODS: We included 77 asymptomatically sensitized
      subjects, 85 allergic patients with acute systemic sting reactions, and 61
      allergic patients currently treated with VIT. Levels of sIgE and sIgG4 to bee and
      vespid venom, rApi m 1, and rVes v 5 were measured immediately after allergic
      sting reactions or before sting challenges and 4 weeks later. All sting
      challenges were tolerated. The inhibitory activity was determined using BAT
      inhibition and ELIFAB assay. RESULTS: Median sIgG4 levels were 96-fold higher in
      VIT patients (P < .001) while sIgE/sIgG4 ratios were consistently lower (P <
      .001). The ELIFAB assay was paralleled by low sIgE/sIgG4 ratios in VIT patients,
      showing markedly higher allergen-blocking capacity (P < .001). An almost complete
      inhibition of the basophil response was seen in all patients treated with vespid
      venom, but not in those treated with bee venom. Four weeks after the sting, sIgE
      and sIgG4 levels were increased in allergic and asymptomatically sensitized
      patients, but not in VIT patients. CONCLUSION: Immunological responses after
      stings varied in bee and vespid venom-allergic patients. In patients under VIT,
      sIgE and sIgG4 remained completely stable after sting challenges. Monitoring VIT
      efficacy was only possible in vespid venom allergy, and the sIgG4 threshold for
      rVes v 5 had the highest sensitivity to confirm tolerance. The BAT inhibition
      test was the most reliable tool to confirm tolerance on an individual basis.

PMID- 29171033
TI  - Actin cytoskeleton remodeling drives epithelial-mesenchymal transition for
      hepatoma invasion and metastasis in mice.
AB  - : High invasiveness is a hallmark of human hepatocellular carcinoma (HCC). Large
      tumors predict invasion and metastasis. Epithelial-mesenchymal transition (EMT)
      is crucial for cancer invasion and metastasis. However, the mechanisms whereby
      large tumors tend to undergo EMT remain unclear. We conducted a subgenome-wide
      screen and identified KLHL23 as an HCC invasion suppressor by inhibiting EMT.
      KLHL23 binds to actin and suppresses actin polymerization. KLHL23 silencing
      induced filopodium and lamellipodium formation. Moreover, EMT was suppressed by
      KLHL23 through its action on actin dynamics. Traditionally, actin cytoskeleton
      remodeling is downstream of EMT reprogramming. It is therefore intriguing to ask
      why and how KLHL23 inversely regulates EMT. Activation of actin cytoskeleton
      remodeling by either KLHL23 silencing or treatment with actin cytoskeleton
      modulators augmented cellular hypoxic responses in a cell-density-dependent
      manner, resulting in hypoxia-inducible factor (HIF) and Notch signals and
      subsequent EMT. Environmental hypoxia did not induce EMT unless actin
      cytoskeleton remodeling was simultaneously activated and only when cells were at
      high density. The resulting EMT was reversed by either adenosine 5'-triphosphate
      supplementation or actin polymerization inhibitors. Down-regulation of KLHL23 was
      associated with invasion, metastasis, and poor prognosis of HCC and pancreatic
      cancer. Correlations of tumor size with EMT and inverse association of expression
      of KLHL23 with HIF/Notch signals were further validated in patient-derived
      xenograft HCCs in mice. CONCLUSION: Simultaneously activation of actin
      cytoskeleton remodeling by intrinsic (such as KLHL23 down-regulation) or
      microenvironment cues is crucial for cell-density-dependent and hypoxia-mediated
      EMT, providing a mechanistic link between large tumor size and
      invasion/metastasis. Our findings provide a means of developing the prevention
      and treatment strategies for tumor invasion and metastasis. (Hepatology
      2018;67:2226-2243).

PMID- 29171034
TI  - Retrospective estimation of the electric and magnetic field exposure conditions
      in in vitro experimental reports reveal considerable potential for uncertainty.
AB  - Experiments on cell cultures exposed to extremely low frequency (ELF, 3-300 Hz)
      magnetic fields are often subject to multiple sources of uncertainty associated
      with specific electric and magnetic field exposure conditions. Here we
      systemically quantify these uncertainties based on exposure conditions described
      in a group of bioelectromagnetic experimental reports for a representative
      sampling of the existing literature. The resulting uncertainties, stemming from
      insufficient, ambiguous, or erroneous description, design, implementation, or
      validation of the experimental methods and systems, were often substantial enough
      to potentially make any successful reproduction of the original experimental
      conditions difficult or impossible. Without making any assumption about the true
      biological relevance of ELF electric and magnetic fields, these findings suggest
      another contributing factor which may add to the overall variability and
      irreproducibility traditionally associated with experimental results of in vitro
      exposures to low-level ELF magnetic fields. Bioelectromagnetics. 39:231-243,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29171035
TI  - Semiparametric regression analysis for alternating recurrent event data.
AB  - Alternating recurrent event data arise frequently in clinical and epidemiologic
      studies, where 2 types of events such as hospital admission and discharge occur
      alternately over time. The 2 alternating states defined by these recurrent events
      could each carry important and distinct information about a patient's underlying
      health condition and/or the quality of care. In this paper, we propose a
      semiparametric method for evaluating covariate effects on the 2 alternating
      states jointly. The proposed methodology accounts for the dependence among the
      alternating states as well as the heterogeneity across patients via a frailty
      with unspecified distribution. Moreover, the estimation procedure, which is based
      on smooth estimating equations, not only properly addresses challenges such as
      induced dependent censoring and intercept sampling bias commonly confronted in
      serial event gap time data but also is more computationally tractable than the
      existing rank-based methods. The proposed methods are evaluated by simulation
      studies and illustrated by analyzing psychiatric contacts from the South Verona
      Psychiatric Case Register.

PMID- 29171036
TI  - Prenatal diagnosis of posterior fossa anomalies: Additional value of chromosomal
      microarray analysis in fetuses with cerebellar hypoplasia.
AB  - OBJECTIVE: To elucidate the relationship between copy number variations (CNVs)
      detected by high-resolution chromosomal microarray analysis (CMA) and the type of
      prenatal posterior fossa anomalies (PFAs), especially cerebellar hypoplasia (CH).
      METHODS: This study involved 77 pregnancies with PFAs who underwent CMA. RESULTS:
      Chromosomal aberrations including pathogenic CNVs and variants of unknown
      significance were detected in 31.2% (24/77) of all cases by CMA and in 18.5%
      (12/65) in fetuses with normal karyotypes. The high detection rate of clinically
      significant CNVs was evident in fetuses with cerebellar hypoplasia (54.6%, 6/11),
      vermis hypoplasia (33.3%, 1/3), and Dandy-Walker malformation (25.0%, 3/12).
      Compare with fetuses without other anomalies, cases with CH and additional
      malformations had the higher CMA detection rate (33.3% vs 88.9%). Three cases of
      isolated unilateral CH with intact vermis and normal CMA result had normal
      outcomes. The deletion of 5p15, 6q terminal deletion, and X chromosome
      aberrations were the most frequent genetic defects associated with cerebellar
      hypoplasia. CONCLUSION: Among fetuses with PFA, those with cerebellar hypoplasia,
      vermis hypoplasia, or Dandy-Walker malformation are at the highest risk of
      clinically significant CNVs. Chromosomal microarray analysis revealed the most
      frequent chromosomal aberrations associated with CH.

PMID- 29171037
TI  - Stochastic phenotype switching leads to intratumor heterogeneity in human liver
      cancer.
AB  - : Intratumor heterogeneity is increasingly recognized as a major factor impacting
      diagnosis and personalized treatment of cancer. We characterized stochastic
      phenotype switching as a mechanism contributing to intratumor heterogeneity and
      malignant potential of liver cancer. Clonal analysis of primary tumor cell
      cultures of a human sarcomatoid cholangiocarcinoma identified different types of
      self-propagating subclones characterized by stable (keratin-7-positive or keratin
      7-negative) phenotypes and an unstable phenotype consisting of mixtures of
      keratin-7-positive and keratin-7-negative cells, which lack stem cell features
      but may reversibly switch their phenotypes. Transcriptome sequencing and
      immunohistochemical studies with the markers Zeb1 and CD146/MCAM demonstrated
      that switching between phenotypes is linked to changes in gene expression related
      but not identical to epithelial-mesenchymal transition. Stochastic phenotype
      switching occurred during mitosis and did not correlate with changes in DNA
      methylation. Xenotransplantation assays with different cellular subclones
      demonstrated increased tumorigenicity of cells showing phenotype switching,
      resulting in tumors morphologically resembling the invasive component of primary
      tumor and metastasis. CONCLUSION: Our data demonstrate that stochastic phenotype
      switching contributes to intratumor heterogeneity and that cells with a switching
      phenotype have increased malignant potential. (Hepatology 2017).

PMID- 29171038
TI  - Effects of exposure to electromagnetic field from 915 MHz radiofrequency
      identification system on circulating blood cells in the healthy adult rat.
AB  - We investigated whether exposure to the 915 MHz radiofrequency identification
      (RFID) signal affected circulating blood cells in rats. Sprague-Dawley rats were
      exposed to RFID at a whole-body specific absorption rate of 2 W/kg for 8 h per
      day, 5 days per week, for 2 weeks. Complete blood counts were performed after
      RFID exposure, and the CD4+ /CD8+ ratio was determined by flow cytometry. The
      number of red blood cells (RBCs) and the values of hemoglobin, hematocrit, and
      RBC indices were increased in the RFID-exposed group compared with those in the
      cage-control and sham-exposed groups (P < 0.05). However, the RBCs and platelet
      numbers were within normal physiologic response ranges. The number of white blood
      cells, including lymphocytes, was decreased in RFID-exposed rats. However, there
      was no statistically significant difference between the sham-exposed and RFID
      exposed groups in terms of T-cell counts or CD4+ /CD8+ ratio (P > 0.05). Although
      the number of circulating blood cells was significantly altered by RFID exposure
      at a whole-body specific absorption rate of 2 W/kg for 2 weeks, these changes do
      not necessarily indicate that RFID exposure is harmful, as they were within the
      normal physiological response range. Bioelectromagnetics. 39:68-76, 2018. (c)
      2017 Wiley Periodicals, Inc.

PMID- 29171039
TI  - One-year follow-up of a TRASER clinical trial for the treatment of nasal
      telangiectasias.
AB  - OBJECTIVES: To evaluate the long-term efficacy of treating nasal telangiectasias
      with the TRASER device. METHODS: Subjects from the TRASER efficacy analysis
      clinical trial were invited for a 1-year follow-up. Standardized photographs were
      taken to compare to baseline. The same clinical trial evaluator graded the
      subjects' current vessel clearance using the 5-point telangiectasia scale. The
      data was compiled and analyzed. RESULTS: Of the subjects with available follow-up
      data, 44% maintained "complete vessel clearance," 44% dropped down one grade to
      "almost complete vessel clearance," and 11% dropped down to "moderately clear
      vessel clearance." All showed clinically significant improvement in nasal
      telangiectasias from baseline. CONCLUSIONS: The TRASER effectively treats nasal
      telangiectasias with minimal to mild recurrence at 1-year follow-up. Lasers Surg.
      Med. 50:61-63, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29171040
TI  - Hypoxia-inducible factor-1alpha/interleukin-1beta signaling enhances hepatoma
      epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory
      microenvironment.
AB  - : The development and progression of hepatocellular carcinoma (HCC) are dependent
      on its local microenvironment. Hypoxia and inflammation are two critical factors
      that shape the HCC microenvironment; however, the interplay between the two
      factors and the involvement of cancer cells under such conditions remain poorly
      understood. We found that tumor-associated macrophages, the primary
      proinflammatory cells within tumors, secreted more interleukin 1beta (IL-1beta)
      under moderate hypoxic conditions due to increased stability of hypoxia inducible
      factor 1alpha (HIF-1alpha). Under persistent and severe hypoxia, we found that
      the necrotic debris of HCC cells induced potent IL-1beta release by tumor
      associated macrophages with an M2 phenotype. We further confirmed that the
      necrotic debris-induced IL-1beta secretion was mediated through Toll-like
      receptor 4/TIR domain-containing adapter-inducing interferon-beta/nuclear factor
      kappa-light-chain-enhancer of activated B cells signaling in a similar, but not
      identical, fashion to lipopolysaccharide-induced inflammation. Using mass
      spectrometry, we identified a group of proteins with O-linked glycosylation to be
      responsible for the necrotic debris-induced IL-1beta secretion. Following the
      increase of IL-1beta in the local microenvironment, the synthesis of HIF-1alpha
      was up-regulated by IL-1beta in HCC cells through cyclooxygenase-2. The
      epithelial-mesenchymal transition of HCC cells was enhanced by overexpression of
      HIF-1alpha. We further showed that IL-1beta promoted HCC metastasis in mouse
      models and was predictive of poor prognosis in HCC patients. CONCLUSION: Our
      findings revealed an HIF-1alpha/IL-1beta signaling loop between cancer cells and
      tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer
      cell epithelial-mesenchymal transition and metastasis; more importantly, our
      results suggest a potential role of an anti-inflammatory strategy in HCC
      treatment. (Hepatology 2018;67:1872-1889).

PMID- 29171041
TI  - TRAF6 regulates proliferation of stromal cells in the transition and peripheral
      zones of benign prostatic hyperplasia via Akt/mTOR signaling.
AB  - BACKGROUND: Increased prostatic smooth muscle tone and hyperplastic growth
      contribute to urethral obstruction and voiding symptoms in benign prostatic
      hyperplasia (BPH). It has been suggested that different proliferative potential
      of stromal cells between transition zone (TZ) and adjoining regions of the
      prostate plays a significant role in the development of BPH. However, the
      molecular mechanisms of this hyperplastic process remain unclear. We found tumor
      necrosis factor receptor-associated factor 6 (TRAF6) highly expressed in TZ
      stromal cells compared to peripheral zone (PZ) stromal cells by gene array
      analyzes. Therefore, we aim to study the potential mechanisms of stromal TRAF6 in
      promoting BPH progression. METHODS: Stromal cells obtained from BPH-derived
      primary cultures. The TRAF6-siRNA vector were constructed and transfected into
      cultured human BPH primary TZ stromal cells, and TRAF6-overexpressing vector were
      constructed and transfected into cultured human BPH primary PZ stromal cells.
      Stromal cells were recombined with BPH-1 cells then subcutaneously inoculated
      into the kidney capsule of male nude mice. Cell proliferation was evaluated by
      CCK-8 assay. Multiple proteins in the Akt/mTOR pathway were assessed using
      western blot. RESULTS: TRAF6 levels were increased in TZ stroma compared with PZ
      stroma of BPH. The in vitro cell culture and in vivo cell recombination revealed
      that selective downregulation of TRAF6 in TZ stromal cells led to suppression of
      the proliferation, while upregulation of TRAF6 in PZ stromal cells enhanced the
      proliferation. We found that the Phosphorylation and Ubiquitination of Akt as
      well as the Phosphorylation of mTOR, P70S6K were decreased when TRAF6 was
      downregulated in primary cultured TZ stromal cells of BPH. CONCLUSIONS: TRAF6 can
      promote the proliferation of stromal cells of BPH via Akt/mTOR signaling. Our
      results may make stromal TRAF6 responsible for zonal characteristic of BPH and as
      a promising therapeutic strategy for BPH treatment.

PMID- 29171042
TI  - The 2D axial transverse views of the fetal face: A new technique to visualize the
      fetal hard palate; methodology description and feasibility.
AB  - OBJECTIVES: The objectives of this study were to describe the methodology and to
      assess the feasibility of a simple 2D ultrasound technique to visualize the fetal
      hard palate (FHP) using a strict axial transverse view (ATV). METHODS:
      Prospective cohort of 100 singleton pregnancies, screened routinely during second
      trimester scans. Three operators imaged the FHP through a strict 2D ATV according
      to a simple methodology. An expert sonographer reviewed all images, and palate
      normality was confirmed at birth. Univariate and multivariate analysis of factors
      modifying the ability to assess the palate were performed. RESULTS: Feasibility
      of imaging the FHP was obtained in 95% of cases with no difference between the
      operators (P = .7). The palate was visualized directly without fetal mobilization
      in 46%. An earlier gestational age at scanning, a prolonged duration of the scan,
      fetal back positioned anteriorly, fetal head flexed, a smaller amniotic pocket,
      and an unmoving fetal limb significantly reduced the feasibility. All failed
      attempts were in fetuses with their back located in anterior and in those with a
      deflexed head. Multivariate analysis did not converge because of the collinearity
      of most parameters. CONCLUSIONS: The ATV is an easy, simple, and accessible 2D
      method to visualize the FHP with no additional time.

PMID- 29171043
TI  - Graphene oxide induces cytotoxicity and oxidative stress in bluegill sunfish
      cells.
AB  - Graphene oxide (GO) is considered a promising material for biological application
      due to its unique properties. However, the potential toxicity of GO to aquatic
      organism particularly bluegill sun fish cells (BF-2) is unexplored or remains
      poorly understood. GO-induced cytotoxicity and oxidative stress in BF-2 cells
      were assessed using a battery of biomarkers. Two different biological assays (3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and neutral red
      uptake were used to evaluate the cytotoxicity of GO on BF-2 cells. It was found
      that GO induced dose- and time-dependent cytotoxicity on BF-2 cells. BF-2 cells
      exposed to lower concentration of GO (40 MUg ml-1 ) for 24 induced morphological
      changes when compared to their respective controls. As evidence for oxidative
      stress lipid peroxidation, superoxide dismutase, catalase, reactive oxygen
      species and 8-hydroxy-2'-deoxyguanosine levels were increased and glutathione
      levels were found to decline in BF-2 cells after treatment with GO. Our findings
      demonstrate that GO when exposed to BF-2 fish cells cause oxidative stress.

PMID- 29171044
TI  - Stemming the Standard-of-Care SPRAWL: Clinician Self-Interest and the Case of
      Electronic Fetal Monitoring.
AB  - The "best interests of the patient" standard-a complex balance between the
      principles of beneficence and autonomy-is the driving force of ethical clinical
      care. Clinicians' fear of litigation is a challenge to that ethical paradigm. But
      is it ever ethically appropriate for clinicians to undertake a procedure with the
      primary goal of protecting themselves from potential legal action? Complicating
      that question is the fact that tort liability is adjudicated based on what most
      clinicians are doing, not the scientific basis of whether they should be doing it
      in the first place. In a court of law, clinicians are generally judged based on
      the "reasonably prudent" standard: what a reasonably prudent practitioner in a
      similar situation would do. But this legal standard can have the effect of
      shifting the medical standard of care-enabling a standard-of-care sprawl where
      actions undertaken for the primary purpose of avoiding liability reset the
      standard of care against which clinicians will be adjudicated. While this problem
      has been recognized in the legal literature, neither current ethical models of
      care nor legal theory offer workable solutions. One of the best examples of the
      conflict between evidence-based medicine and common clinical practice is the use
      of electronic fetal monitoring. Despite strong evidence and professional
      guidelines that argue against the use of EFM for healthy pregnancies, the
      practice persists. One of the main reasons for this is often assumed to be
      physicians' concerns about liability.

PMID- 29171045
TI  - Being Better Bodies.
AB  - Bioethics has an uneasy relationship with embodiment. Only with vigilance does
      knowledge of the body as it is lived counterbalance the momentous inertia of
      knowledge of the body as an object brought about by modern medical sciences. As a
      field tethered to detached, technical ways of knowing the world, bioethics must
      toil to treat the body as more than mere material and machine. To be more is,
      among other things, to be social-to live in the thickets of interdependence and
      the institutions and practices we build, hone, and defend to facilitate it. I
      take this tension to define the ultimate stakes of Melinda Hall's The Bioethics
      of Enhancement: Transhumanism, Disability, and Biopolitics. Hall homes in on
      transhumanism, the idea that we should embrace technology to vault beyond current
      human limitations. Yet the work serves as a reminder for all bioethicists and
      philosophers of how easily one can be led astray by otherwise irreproachable
      values when they are disconnected from the conditions and realities of human
      life, including being irremediably interdependent embodied beings. Put more
      acerbically, the book is a reminder of how thinking goes wrong when divorced from
      the principal sources out of which human appraisals emerge: our fleshy, messy,
      social bodies.

PMID- 29171046
TI  - Delegating Informed Consent.
AB  - Ten years ago, Megan Shinal sought the care of neurosurgeon Steven Toms for the
      surgical treatment of a recurrent nonmalignant tumor in the pituitary region of
      her brain. In their twenty-minute meeting, Shinal did not make a final decision
      about which surgical approach she wished to pursue. Subsequently, she spoke with
      Tom's physician assistant once by phone and once in person, when she signed the
      consent form, which did not appear to designate which surgical approach she had
      chosen. During the operation-a total resection-Toms perforated Shinal's carotid
      artery, resulting in hemorrhage, stroke, brain injury, and partial blindness. The
      jury found that Toms had fulfilled his informed-consent obligations prior to
      performing the resection; however, in June 2017, the Supreme Court of
      Pennsylvania overturned the decision, relying on the Pennsylvania Medical Care
      Availability and Reduction of Error Act. The court found that the language of the
      act is unambiguous in its requirement that "a physician's duty to provide
      information to a patient sufficient to obtain her informed consent is non
      delegable." Presumably, this rule of nondelegation applies beyond the surgical
      theater to other major treatment decisions. And it is unclear whether it applies
      to other professionals in a subordinate position to the treating physician, such
      as residents and fellows.

PMID- 29171048
TI  - Erratum.

PMID- 29171047
TI  - Ending DACA Has Pragmatic and Ethical Implications for U.S. Health Care.
AB  - In 2012, Loyola University Chicago's Stritch School of Medicine became the first
      medical school in the United States to actively recruit and accept undocumented
      immigrants who received protections granted under the Deferred Action for
      Childhood Arrivals program that was established by presidential memorandum. By
      2016, sixty-one medical schools were considering applications from DACA
      recipients for admission, and more than 110 students applied. According to the
      American Association of Medical Colleges, sixty-five DACA recipients matriculated
      in U.S. medical schools in the 2016-2017 school year. These students contribute
      both diversity and talent to our medical community; they could also have a
      significant impact on the care of underserved and immigrant populations. The
      recent decision by the Trump administration to rescind DACA therefore comes with
      serious pragmatic and ethical ramifications, impeding our medical community's
      efforts to develop a diverse and representative workforce committed to improving
      access to quality care for all patients.

PMID- 29171049
TI  - Public Health Autonomy: A Critical Reappraisal.
AB  - The ethical principle of autonomy is among the most fundamental in ethics, and it
      is particularly salient for those in public health, who must constantly balance
      the desire to improve health outcomes by changing behavior with respect for
      individual freedom. Although there are some areas in which there is a genuine
      tension between public health and autonomy-childhood vaccine mandates, for
      example-there are many more areas where not only is there no tension, but public
      health and autonomy come down to the same thing. These areas of overlap are often
      rendered invisible by a thin understanding of autonomy. Better integrating newer
      theoretical insights about autonomy into applied ethics can make discussions of
      public health ethics more rigorous, incisive, and effective. Even more
      importantly, bringing modern concepts of autonomy into public health ethics can
      showcase the many areas in which public health and autonomy have the same goals,
      face the same threats, and can be mutually advanced by the same kinds of
      solutions. This article provides a schema for relational autonomy in a public
      health context and gives concrete examples of how autonomy can be served through
      public-health interventions. It marshals insights from sociology, psychology, and
      philosophy to advance a theory of autonomy and coercion that recognizes three
      potential threats to autonomy: threats to choice sets, threats to knowledge, and
      threats to preferences.

PMID- 29171050
TI  - Contemplating Resectability.
AB  - Suzie loves to talk. A successful mid-thirties businesswoman, she is a self
      described social butterfly-which made her diagnosis of tongue cancer even more
      devastating. She came to the clinic complaining of a lump in her throat, which in
      most young healthy people turns out to be benign and easily treated. But not for
      Suzie, who had a very rare salivary tumor arising in the back of her tongue. Its
      slow growth was both a blessing and a curse; such tumors do not kill people
      quickly, but they typically require surgery. It would slowly and relentlessly
      grow until and unless we removed most of her tongue. In head and neck surgery,
      issues of appearance, identity, function, and communication are the foremost
      considerations when we decide when, and whether, to operate. As the adage goes,
      knowing when not to operate is the sine qua non of the wise surgeon. But the
      inverse is also true.

PMID- 29171051
TI  - The Real-World Ethics of Adaptive-Design Clinical Trials.
AB  - From the earliest application of modern randomized controlled trials in medical
      research, scientists and observers have deliberated the ethics of randomly
      allocating study participants to trial control arms. Adaptive RCT designs have
      been promoted as ethically advantageous over conventional RCTs because they
      reduce the allocation of subjects to what appear to be inferior treatments.
      Critical assessment of this claim is important, as adaptive designs are changing
      medical research, with the potential to significantly shift how clinical trials
      are conducted. Policy-makers are swiftly moving to encourage greater use of
      adaptive designs. In 2016, the newly enacted 21st Century Cures Act instructed
      the Food and Drug Administration to help product sponsors incorporate adaptive
      methods into proposed clinical trial protocols and applications for
      investigational drugs and also biological products. In this article, we review
      the ethical justifications commonly offered for adaptive designs, explore these
      arguments in the context of actual trials, and contend that clinical equipoise is
      a useful standard for adaptive-trial ethics. We distinguish between theoretical
      and clinical equipoise and explain why ethical arguments related to adaptive
      trials tend to focus on the former. Yet we contend that theoretical equipoise can
      be an unreliable standard for adaptive ethics. While we contend that clinical
      equipoise is the most critical principle for the primary ethical concerns posed
      by adaptive trials, we suggest ethical approaches to deal with some additional
      concerns unique to adaptive designs.

PMID- 29171052
TI  - Social Practices.
AB  - In one way or another, several pieces in the November-December 2017 of the
      Hastings Center Report reflect an insistence on turning away from abstractions to
      learn how a whole community understands a problem at issue-how a community
      understands what's at stake in individuals' autonomous choices, how a community
      understands the results of a clinical trial, how a community understands, and
      generates and adjusts, medical standards. In the lead article, Kayte Spector
      Bagdady and colleagues argue that, given extensive research showing that
      electronic fetal monitoring during childbirth offers very little benefit to the
      mother and child, a mechanism is needed to ensure that the medical standard of
      care is based on the right kinds of considerations. The core claim of the second
      article, by Laura Bothwell and Aaron Kesselheim, is that adaptive-trial designs
      are premised on the idea that trial designs should be maximally persuasive to the
      medical community. In the third article, Frederick Zimmerman argues that a richer
      understanding of autonomy makes it possible to see that public health is more
      frequently compatible with autonomy than is commonly recognized. A supplement to
      the issue contains a special report that explores what "just reproduction" means
      "in the face of multifarious understandings of both justice and autonomy and in
      light of increasingly complex and costly reproductive technologies."

PMID- 29171054
TI  - The Sticky Standard of Care.
AB  - The problem at the heart of "Stemming the Standard-of-Care Sprawl: Clinician Self
      Interest and the Case of Electronic Fetal Monitoring," an article by Kayte
      Spector-Bagdady and colleagues in the November-December 2017 issue of the
      Hastings Center Report, is the persistence of a suboptimal standard of care long
      after evidence-driven approaches would dictate a change. That problem is not
      simply defensive medicine, or what the authors call "standard-of-care sprawl."
      Instead, it is that, in some cases, the standard of care lags behind best
      practices. It gets stuck. The authors point to the genesis of the stickiness
      problem in their passing reference to a core truth: "The problem is that standard
      of care is not synonymous with best or evidence-based medicine." In my view, we
      might best understand the persistence of ineffective and even harmful medical
      interventions by acknowledging the regulatory vacuum in which such practices
      thrive. It is by default, not by design, that the profession relies on medical
      malpractice law to set the boundaries on acceptable practice.

PMID- 29171055
TI  - Global bioethics.
AB  - This August, I participated in the conference "Genome Editing: Biomedical and
      Ethical Perspectives," hosted by the Center for the Study of Bioethics at the
      University of Belgrade and cosponsored by the Division of Medical Ethics of NYU
      Langone Health and The Hastings Center. The prime minister of Serbia, Ana
      Brnabic, spoke of the significance of bringing together an international
      community of bioethicists, acknowledging that ethical, social, and legal issues
      surrounding gene editing technologies transcend national boundaries. Europe's
      Oviedo Convention prohibits human germline gene editing, and UNESCO's Universal
      Declaration on the Human Genome and Human Rights says that germline editing
      "could be contrary to human dignity," an assault on humanity itself. Whether one
      agrees or not, engaging with the idea forces us to think about what it means to
      be part of the global human community and about the moral significance of the
      human genome to creating that community. The conference highlighted for me how
      challenging having international, much less global, conversations about bioethics
      can be.

PMID- 29171056
TI  - "What's in a name?" CAR-T Gene Therapy.

PMID- 29171057
TI  - Real-World Evidence, Public Participation, and the FDA.
AB  - For observers of pharmaceutical regulation and the Food and Drug Administration,
      these are uncertain times. Events in late 2016 raised concerns that the FDA's
      evidentiary standards were being weakened, compromising the agency's ability to
      adequately perform its regulatory and public health responsibilities. Two
      developments most directly contributed to these fears-the approval of eteplirsen,
      a treatment for Duchenne muscular dystrophy, against the recommendations of both
      FDA staff and an advisory committee and the December 2016 signing of the 21st
      Century Cures Act, which encouraged greater use by the FDA of "real-world"
      evidence not obtained through randomized controlled trials. The arrival of the
      Trump administration-with its deregulatory, industry-friendly approach-has only
      amplified concerns over the future of the FDA. It is too early to know whether
      the recent developments are truly harbingers of an FDA less likely to prevent
      unsafe or ineffective products from reaching the market. But elements in the two
      events-the role of patient narratives in deliberations regarding eteplirsen and
      the enthusiasm for real-world evidence in the 21st Century Cures Act-raise
      critical issues for the future of evidence in the FDA's work. The rigorous,
      inclusive approach under way to consider issues related to real-world evidence
      provides a model for a similarly needed inquiry regarding public participation in
      FDA decision-making.

PMID- 29171058
TI  - Ultrasound in Total Hip Replacement: Value of Anterior Acetabular Cup Visibility
      and Contact With the Iliopsoas Tendon.
AB  - OBJECTIVES: To assess visibility of the acetabular cup in total hip replacement
      and to determine the value of direct and indirect signs of iliopsoas impingement
      syndrome with ultrasound. METHODS: Ultrasound examinations were performed by a
      single operator in 17 patients with iliopsoas impingement syndrome and 48 control
      patients. Cup visibility, contact between the cup and psoas tendon, and the
      presence of indirect signs of iliopsoas impingement syndrome were investigated in
      all patients. When the acetabular cup was visible, its size and position in
      relation to the psoas tendon were recorded. RESULTS: Anterior cup visibility (P =
      .03), contact with the psoas tendon (P < .001), psoas tendinopathy (P = .02), and
      iliopsoas bursitis (P < .001) were significantly associated with iliopsoas
      impingement syndrome, the latter reported with specificity of 100%. In the
      sagittal plane at the level of the psoas tendon, a maximum sagittal length of
      greater than 5 mm and a posteroanterior cup shift of 3 mm or greater yielded
      respective sensitivities of 82% and 59% and specificities of 81% and 100%.
      CONCLUSIONS: When iliopsoas impingement syndrome is clinically suspected, the
      presence of iliopsoas bursitis or a posteroanterior cup shift of greater than 3
      mm under the psoas tendon serve to confirm the diagnosis. In the absence of these
      conditions, a therapeutic test may be necessary because of the incomplete, albeit
      high, specificity of other signs.

PMID- 29171059
TI  - Family and individual variables associated with young Filipino children's
      numeracy interest and competence.
AB  - Children's early numeracy outcomes set the foundation for mathematics learning in
      their future school years. This study examined how different family and
      individual variables were associated with the numeracy interest and competence of
      disadvantaged young children in the Philippines. The numeracy and literacy skills
      of 673 children living in low-middle income communities were tested. Their
      parents were also asked to complete a questionnaire on demographics, their home
      numeracy practices, attitudes about numeracy learning, and children's numeracy
      interest. Structural equation modelling analyses showed that children's numeracy
      interest was linked with their parents' practices and attitudes. Children's
      numeracy competence, on the other hand, was related to their gender, age,
      socioeconomic status, and literacy abilities. These findings suggest that family
      and individual variables might play different roles in disadvantaged children's
      early numeracy development. Moreover, parents can be encouraged to make effective
      use of home numeracy experiences to promote their children's numeracy competence.
      Statement of contribution What is already known on this subject? In developed
      countries, home environment is occasionally found to link with early numeracy
      development. Some individual variables are also found to play significant roles
      in early numeracy development. What does this study add? Among young Filipino
      children from disadvantaged backgrounds, home environment is related to numeracy
      interest. Family socioeconomic status plays a significant role in early numeracy
      competence. Early literacy and numeracy skills are interrelated with each other.

PMID- 29171060
TI  - Suitability of microDiamond detectors for the determination of absorbed dose to
      water around high-dose-rate 192 Ir brachytherapy sources.
AB  - PURPOSE: Experimental dosimetry of high-dose-rate (HDR) 192 Ir brachytherapy (BT)
      sources is complicated due to high dose and dose-rate gradients, and softening of
      photon energy spectrum with depth. A single crystal synthetic diamond detector
      microDiamond (PTW 60019, Freiburg, Germany) has a small active volume, high
      sensitivity, direct readout, and nearly water-equivalent active volume. The
      purpose of this study was to evaluate the suitability of microDiamond detectors
      for the determination of absorbed dose to water around HDR 192 Ir BT sources.
      Three microDiamond detectors were used, allowing for the comparison of their
      properties. METHODS: In-phantom measurements were performed using microSelectron
      and VariSource iX HDR 192 Ir BT treatment units. Their treatment planning systems
      (TPSs), Oncentra (v. 4.3) and BrachyVision (v. 13.6), respectively, were used to
      create irradiation plans for a cubic PMMA phantom with the microDiamond
      positioned at one of three source-to-detector distances (SDDs) (1.5, 2.5, and 5.5
      cm) at a time. The source was stepped in increments of 0.5 cm over a total length
      of 6 cm to yield absorbed dose of 2 Gy at the nominal reference-point of the
      detector. Detectors were calibrated in 60 Co beam in terms of absorbed dose to
      water, and Monte Carlo (MC) calculated beam quality correction factors were
      applied to account for absorbed-dose energy dependence. Phantom correction
      factors were applied to account for differences in dimensions between the
      measurement phantom and a water phantom used for absorbed dose calculations made
      with a TPS. The same measurements were made with all three of the detectors.
      Additionally, dose-rate dependence and stability of the detectors were evaluated
      in 60 Co beam. RESULTS: The percentage differences between experimentally
      determined and TPS-calculated absorbed doses to water were from -1.3% to +2.9%.
      The values agreed to within experimental uncertainties, which were from 1.9% to
      4.3% (k = 2) depending on the detector, SDD and treatment delivery unit. No dose
      rate or intrinsic energy dependence corrections were applied. All microDiamonds
      were comparable in terms of preirradiation dose, stability of the readings and
      energy response, and showed a good agreement. CONCLUSIONS: The results indicate
      that the microDiamond is potentially suitable for the determination of absorbed
      dose to water around HDR 192 Ir BT sources and may be used for independent
      verification of TPS's calculations, as well as for QA measurements of HDR 192 Ir
      BT treatment delivery units at clinical sites.

PMID- 29171061
TI  - "Hosting" an implantable cardioverter defibrillator: A phenomenological inquiry.
AB  - Implantable cardioverter defibrillators (ICDs) can reduce unexpected cardiac
      mortality, but they also have a dramatic impact on a patient's quality of life.
      We aimed to explore ICD recipients' experiences in order to foster improvements
      in the quality of care. Analyses were done using a descriptive phenomenological
      method, based on qualitative interview data from a purposive sample of 20 ICD
      recipients. Four main themes emerged: living with fear; relying on technology;
      knowing about the ICD and how to live with it; and coping with the effects of the
      ICD on daily life. ICD recipients lived in a constant state of fear due to the
      presence of the device and the uncertainty related to the potential electrical
      shocks it could deliver. This fear was compounded by changes that severely
      affected the quality of their daily life. ICD recipients felt they were always on
      the brink of death, and that although they received sufficient technical
      information they did not feel they received meaningful information to help them
      accept, live with, and cope with the device. Emotional information and support,
      rather than technical information, must be provided to ICD recipients to give
      them the ability to cope with the everyday threats they perceive because of the
      device. Qualitative evidence may help professionals tackle known threats to
      patients' quality of life and increase the quality of care.

PMID- 29171062
TI  - Mixture drug-count response model for the high-dimensional drug combinatory
      effect on myopathy.
AB  - Drug-drug interactions (DDIs) are a common cause of adverse drug events (ADEs).
      The electronic medical record (EMR) database and the FDA's adverse event
      reporting system (FAERS) database are the major data sources for mining and
      testing the ADE associated DDI signals. Most DDI data mining methods focus on
      pair-wise drug interactions, and methods to detect high-dimensional DDIs in
      medical databases are lacking. In this paper, we propose 2 novel mixture drug
      count response models for detecting high-dimensional drug combinations that
      induce myopathy. The "count" indicates the number of drugs in a combination. One
      model is called fixed probability mixture drug-count response model with a
      maximum risk threshold (FMDRM-MRT). The other model is called count-dependent
      probability mixture drug-count response model with a maximum risk threshold
      (CMDRM-MRT), in which the mixture probability is count dependent. Compared with
      the previous mixture drug-count response model (MDRM) developed by our group,
      these 2 new models show a better likelihood in detecting high-dimensional drug
      combinatory effects on myopathy. CMDRM-MRT identified and validated (54; 374;
      637; 442; 131) 2-way to 6-way drug interactions, respectively, which induce
      myopathy in both EMR and FAERS databases. We further demonstrate FAERS data
      capture much higher maximum myopathy risk than EMR data do. The consistency of 2
      mixture models' parameters and local false discovery rate estimates are evaluated
      through statistical simulation studies.

PMID- 29171063
TI  - Enzyme-linked immunosorbent assays (ELISA) based on thread, paper, and fabric.
AB  - This paper describes enzyme-linked immunosorbent assays (ELISAs) utilizing
      microfluidic thread/paper-based analytical devices (MUTPAD), microfluidic fabric
      based analytical devices (MUFAD), and microfluidic thread-based analytical
      devices (MUTAD). Here, the quantitative detection of biotinylated goat anti-mouse
      IgG (system one) and rabbit IgG (system two) antibodies via colorimetric analysis
      is detailed. In both systems, antibody is spotted on the detection site and
      subjected to a series of washes, addition of streptavidin-alkaline phosphatase
      (Strep-ALP) (system 1) or alkaline phosphatase (ALP)-conjugated secondary
      antibody (system 2), and colorimetric substrate. The devices are scanned and
      analyzed yielding a correlation between inverse yellow (or purple) intensity. For
      system one, a linear range of detection at low concentrations of streptavidin
      alkaline phosphatase (Strep-ALP) was observed befire the enzyme reached a Vmax .
      At higher concentrations of Strep-ALP, saturation is achieved for both the MUTPAD
      and MUFAD devices. For system two, the IC50 values obtained for the non
      trifurcated and trifurcated MUTADs were determined to be 180.2 fmol/zone and
      133.8 fmol/zone, respectively. The IC50 value was demonstrated to be 1034
      fmol/zone and 208.6 fmol/zone for the MUTPADs and MUFADs, respectively. For all
      devices the lowest concentration of Strep-ALP or rabbit IgG used in the assay was
      3.75 * 10-4  mg/mL and 0.7 fmol/zone, respectively. The development of this
      technology should further facilitate the use of these platforms for ELISA to
      detect and quantitate antibodies.

PMID- 29171064
TI  - Analysis of ear side of mobile phone use in the general population of Japan.
AB  - This study aimed to clarify the distribution of the ear side of mobile phone use
      in the general population of Japan and clarify what factors are associated with
      the ear side of mobile phone use. Children at elementary and junior high schools
      (n = 2,518) and adults aged >=20 years (n = 1,529) completed an Internet-based
      survey. Data were subjected to a logistic regression analysis. In children, due
      to the tendency to use the dominant hand, we analyzed the factors associated with
      the use of right ear in right-handed people. Statistically significant
      differences were observed only in talk time per call (odds ratio (OR) = 2.17; 95%
      confidence interval (CI): 1.22-3.99). In adults, due to the tendency to use the
      left ear, we analyzed factors associated with the use of left ear in right-handed
      people. Significant differences were observed in those aged 30-39 years (OR =
      2.55; 95% CI: 1.79-3.68), those aged 40-49 years (OR = 3.08; 95% CI: 2.15-4.43),
      those aged >50 years (OR = 1.85; 95% CI: 1.20-2.85), and in those with a
      percentage of total talk time when using mobile phones at work of 51-100% (OR =
      1.75; 95% CI: 1.21-2.55). We believe that future epidemiological studies on
      mobile phone use can be improved by considering the trends in mobile phone use
      identified in this study. Bioelectromagnetics. 39:53-59, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29171065
TI  - Peptic ulcer bleeding in patients with cirrhosis: Is it as bad as variceal
      bleeding?

PMID- 29171066
TI  - Association of Serum Vitamin D Level and Carotid Atherosclerosis: A Systematic
      Review and Meta-analysis.
AB  - Vitamin D deficiency is associated with an increased risk of subclinical
      atherosclerosis. To explore the potential link of the serum vitamin D level with
      carotid atherosclerosis, this meta-analysis assessed the correlation between
      vitamin D and carotid intima-media thickness as well as carotid atherosclerotic
      plaque. PubMed, Embase, Web of Science, and Cochrane Library databases were
      searched until the end of March 2017. Clinical studies investigating the
      relationship between vitamin D and carotid atherosclerosis were included. The
      outcome data were extracted according to the inclusion criteria and pooled for an
      effect estimate by a random-effects model. Of the 506 initially retrieved
      studies, 11 studies involving a total of 16,434 participants were included in the
      meta-analysis. Newcastle-Ottawa Quality Assessment Scale scores suggested that
      the included studies were of high quality. The pooled effects estimate showed
      that the serum vitamin D level was negatively associated with carotid
      atherosclerosis (odds ratio, 0.95; 95% confidence interval [CI], 0.93-0.96), with
      substantial heterogeneity among the individual studies (I2  = 54%). Furthermore,
      a subgroup analysis suggested that hypovitaminosis D was associated with an 0.85
      fold decrease in the odds of having a higher carotid intima-media thickness (95%
      CI, 0.76-0.96; P < .05; I2  = 69%). Additionally, the pooled analysis also
      indicated that the serum vitamin D level was a protective factor against
      increased carotid plaque (odds ratio, 0.95; 95% CI, 0.93-0.97; P < .05; I2  =
      29%). Funnel plots and the Egger regression test showed the absence of a
      publication bias. In this meta-analysis, we comprehensively revealed a close link
      between vitamin D deficiency and carotid atherosclerosis. Patients with
      hypovitaminosis D might have extra requirements for preventive and therapeutic
      measures against early atherosclerosis, thus reducing the cardiovascular disease
      risk in the long term.

PMID- 29171067
TI  - Toward Scintillator High-Gain Avalanche Rushing Photoconductor Active Matrix Flat
      Panel Imager (SHARP-AMFPI): Initial fabrication and characterization.
AB  - PURPOSE: We present the first prototype Scintillator High-Gain Avalanche Rushing
      Photoconductor Active Matrix Flat Panel Imager (SHARP-AMFPI). This detector
      includes a layer of avalanche amorphous Selenium (a-Se) (HARP) as the
      photoconductor in an indirect detector to amplify the signal and reduce the
      effects of electronic noise to obtain quantum noise-limited images for low-dose
      applications. It is the first time avalanche a-Se has been used in a solid-state
      imaging device and poses as a possible solution to eliminate the effects of
      electronic noise, which is crucial for low-dose imaging performance of AMFPI.
      METHODS: We successfully deposited a solid-state HARP structure onto a 24 * 30
      cm2 array of thin-film transistors (TFT array) with a pixel pitch of 85 MUm. The
      HARP layer consists of 16 MUm of a-Se with a hole-blocking and electron-blocking
      layer to prevent charge injection from the high-voltage bias and pixel
      electrodes, respectively. An electric field (ESe ) up to 105 V MUm-1 was applied
      across the a-Se layer without breakdown. A 150 MUm thick-structured CsI:Tl
      scintillator was used to form SHARP-AMFPI. The x-ray imaging performance is
      characterized using a 30 kVp Mo/Mo beam. We evaluate the spatial resolution,
      noise power, and detective quantum efficiency at zero frequency of the system
      with and without avalanche gain. The results are analyzed using cascaded linear
      system model (CLSM). RESULTS: An avalanche gain of 76 +/- 5 was measured at ESe =
      105 V MUm-1 . We demonstrate that avalanche gain can amplify the signal to
      overcome electronic noise. As avalanche gain is increased, image quality improves
      for a constant (0.76 mR) exposure until electronic noise is overcome. Our system
      is currently limited by poor optical transparency of our high-voltage electrode
      and long integrating time which results in dark current noise. These two effects
      cause high-spatial frequency noise to dominate imaging performance. CONCLUSIONS:
      We demonstrate the feasibility of a solid-state HARP x-ray imager and have
      fabricated the largest active area HARP sensor to date. Procedures to reduce
      secondary quantum and dark noise are outlined. Future work will improve optical
      coupling and charge transport which will allow for frequency DQE and temporal
      metrics to be obtained.

PMID- 29171069
TI  - List of Referees.

PMID- 29171068
TI  - A T-cell diagnostic test for cystic echinococcosis based on Antigen B peptides.
AB  - Cystic echinococcosis (CE) immunodiagnosis is still imperfect. We recently set-up
      a whole-blood test based on the interleukin (IL)-4 response to the native Antigen
      B (AgB) of Echinococcus granulosus. However, AgB is encoded by a multigene family
      coding for five putative subunits. Therefore, the aims of this study were to
      analyse the IL-4 response to peptides spanning the immunodominant regions of the
      five AgB subunits and to evaluate the accuracy of this assay for CE diagnosis.
      Peptides corresponding to each subunit were combined into five pools. A pool
      containing all peptides was also used (total pool). IL-4 evaluated by enzyme
      linked immunosorbent assay was significantly higher in patients with CE compared
      to those without (NO-CE subjects) when whole-blood was stimulated with AgB1 and
      with the total pool. Moreover, IL-4 levels in response to the total pool were
      significantly increased in patients with active cysts. Receiver Operator Curve
      analysis identified a cut-off point of 0.59 pg/mL predicting active cysts
      diagnosis with 71% sensitivity and 82% specificity in serology-positive CE
      patients. These data, if confirmed in a larger cohort, offer the opportunity to
      develop new diagnostic tools for CE based on a standardized source of AgB as the
      peptides.

PMID- 29171070
TI  - Music for reducing the anxiety and pain of patients undergoing a biopsy: A meta
      analysis.
AB  - AIM: This study aimed to evaluate the efficacy of music therapy for reducing the
      anxiety and pain of patients who underwent a biopsy. BACKGROUND: Music can affect
      human anxiety and pain by triggering a neuroendocrine effect. Clinical study
      results indicated that music can influence the anxiety and pain caused by
      invasive procedures. There is no effective solution for anxiety and pain arising
      from a biopsy. Although researchers in this field have different views, music
      still holds promise in reducing the anxiety and pain in patients undergoing the
      biopsy. DESIGN: Systematic review and meta-analysis of randomized controlled
      trials. DATA SOURCES: Systematic searches were conducted in PubMed, Embase,
      Medline and Cochrane databases for studies reported in the English language. The
      review period covered 2000 - December 2016. The outcome measure of interest was
      anxiety and pain. METHODS: This review followed Cochrane methods. Studies were
      selected according to the PICOS framework. The methodological quality of studies
      was assessed with the Cochrane risk of bias tool. A systematic review of
      effectiveness was conducted by using GRADE approach. RESULTS: Nine randomized
      controlled trials with a total of 326 participants in the music intervention
      group and 323 controls met the inclusion criteria. Music had a tendency towards
      decreasing systolic blood pressure before the biopsy, State-Trait Anxiety
      Inventory scores after the biopsy, diastolic blood pressure after the biopsy and
      heart rate after the biopsy. Similarly, music also tended to be more effective
      for controlling pain after the biopsy. There was moderate quality evidence for
      the outcome: State-Trait Anxiety Inventory scores after the biopsy; and low- or
      very low-quality evidence for other outcomes. CONCLUSION: Music can be used for
      patients before and during the biopsy procedure. This approach may be performed
      by nurses to promote the recovery of patients after the biopsy.

PMID- 29171071
TI  - Person-centred, web-based support in pregnancy and early motherhood for women
      with Type 1 diabetes mellitus: a randomized controlled trial.
AB  - AIMS: To report results from and explore use of a multicentre, parallel-group,
      unblinded, randomized controlled trial testing the effectiveness in terms of well
      being and diabetes management of a person-centred, web-based support programme
      for women with Type 1 diabetes, in pregnancy and postpartum. METHODS: Between
      2011 and 2014, 174 pregnant women with Type 1 diabetes were randomly allocated
      (1:1) to web-based support and standard care (intervention group, n=83), or
      standard care (control group, n=91). The web-based support consisted of evidence
      based information; a self-care diary for monitoring of daily activities; and peer
      support in a discussion forum. The primary outcomes (mean difference, measured at
      6 months after childbirth) were well-being and diabetes management. RESULTS: No
      differences were found with regard to the primary outcome measure scores for
      general well-being [1.04 (95% CI -1.28 to 3.37); P=0.68] and self-efficacy of
      diabetes management [0.08 (95% CI -0.12 to 0.28); P= 0.75], after adjustment for
      baseline differences in the insulin administration method, nor with regard to the
      secondary outcome measures. CONCLUSIONS: At 6 months after childbirth, the web
      based support plus standard care was not superior to standard care in terms of
      general well-being or self-efficacy of diabetes management. This might be
      explained by the low number of participants who had a high activity level. Few
      simultaneously active participants in the web-based programme and stressors in
      motherhood and diabetes postpartum were the main barriers to its use. Further
      intervention studies that offer web-based support are needed, with lessons
      learned from the present study. (Clinicaltrials.gov identification number:
      NCT015665824).

PMID- 29171072
TI  - Proteomic profiling of integral membrane proteins associated to pathogenicity in
      Vibrio parahaemolyticus strains.
AB  - Vibrio parahaemolyticus has been recognized as the causal agent of early
      mortality syndrome and is currently considered an emerging shrimp disease causing
      losses of millions in the aquaculture industry. Integral membrane proteins are
      widely recognized as pathogenicity factors involved in essential mechanisms for
      V. parahaemolyticus infection, which makes them attractive as therapeutic
      targets. However, their physico-chemical properties and weak expression has
      resulted in under-representation of these proteins in conventional bottom-up
      proteomics, making integral membrane proteomics a challenging task. Integral
      membrane proteins from a bacterial strain isolated from the hepatopancreases of
      white shrimp with early mortality syndrome and identified by 16S rRNA sequencing
      as V. parahaemolyticus and an ATCC strain that is pathogenic for humans were
      obtained by a sequential extraction method and subjected to relative
      quantification and identification by isobaric Tags for Relative and Absolute
      Quantitation. A homology database search resulted in identification of more than
      two hundred proteins, 35 of which are recognized as pathogenic factors showed
      statistically significant differential accumulation between the strains. These
      proteins are mainly associated with adherence, secretion systems, cell division,
      transport, lysogenization, movement and virulence. Identification of
      pathogenicity-related proteins in V. parahaemolyticus provides valuable
      information for developing strategies based on molecular mechanisms that inhibit
      these proteins, which may be useful therapeutic targets for assisting the shrimp
      and aquaculture industry.

PMID- 29171074
TI  - Invited commentary: The ageing of populations across the globe and implications
      for the future of the dental profession.

PMID- 29171073
TI  - Evaluation of Francisella tularensis DeltapdpC as a candidate live attenuated
      vaccine against respiratory challenge by a virulent SCHU P9 strain of Francisella
      tularensis in a C57BL/6J mouse model.
AB  - Francisella tularensis, which causes tularemia, is an intracellular gram-negative
      bacterium. F. tularensis has received significant attention in recent decades
      because of its history as a biological weapon. Thus, development of novel
      vaccines against tularemia has been an important goal. The attenuated F.
      tularensis strain DeltapdpC, in which the pathogenicity determinant protein C
      gene (pdpC) has been disrupted by TargeTron mutagenesis, was investigated as a
      potential vaccine candidate for tularemia in the present study. C57BL/6J mice
      immunized s.c. with 1 * 106 CFUs of DeltapdpC were challenged intranasally with
      100* the median lethal dose (LD50 ) of a virulent SCHU P9 strain 21 days post
      immunization. Protection against this challenge was achieved in 38% of immunized
      C57BL/6J mice administered 100 LD50 of this strain. Conversely, all unimmunized
      mice succumbed to death 6 days post challenge. Survival rates were significantly
      higher in vaccinated than in unimmunized mice. In addition, DeltapdpC was
      passaged serially in mice to confirm its stable attenuation. Low bacterial loads
      persisted in mouse spleens during the first to tenth passages. No statistically
      significant changes in the number of CFUs were observed during in vivo passage of
      DeltapdpC. The inserted intron sequences for disrupting pdpC were completely
      maintained even after the tenth passage in mice. Considering the stable
      attenuation and intron sequences, it is suggested that DeltapdpC is a promising
      tularemia vaccine candidate.

PMID- 29171075
TI  - Geriatrics, disabilities, dentistry, ethics and economics.

PMID- 29171076
TI  - Impact of weight stigma on physiological and psychological health outcomes for
      overweight and obese adults: A systematic review.
AB  - AIM: To summarize the associations between weight stigma and physiological and
      psychological health for individuals who are overweight or obese. BACKGROUND:
      Weight stigma can be defined as individuals experiencing verbal or physical abuse
      secondary to being overweight or obese. Weight stigma has negative consequences
      for both physiological and psychological health. DESIGN: A quantitative
      systematic review. DATA SOURCES: PubMed, PsycINFO, CINAHL and MEDLINE from 1
      January 2008 - 30 July 2016. REVIEW METHODS: A systematic review was conducted
      using the Cochrane Collaboration guidelines, the PRISMA statement guidelines and
      the quality assessment from the National Heart, Lung and Blood Institute.
      Inclusion criteria consisted of quantitative studies that examined the
      associations between weight stigma and physiological and psychological health
      outcomes in adults who were overweight or obese. Exclusion criteria consisted of
      qualitative studies, literature reviews, expert opinions, editorials and reports
      on weight stigma without health outcomes or with behavioural outcomes and
      intervention studies that reduced weight stigma. A quality appraisal of the
      selected studies was conducted. RESULTS: A total of 33 studies met the
      eligibility criteria. Weight stigma was positively associated with obesity,
      diabetes risk, cortisol level, oxidative stress level, C-reactive protein level,
      eating disturbances, depression, anxiety, body image dissatisfaction and
      negatively associated with self-esteem among overweight and obese adults.
      CONCLUSION: Weight stigma is associated with adverse physiological and
      psychological outcomes. This conclusion highlights the need to increase public
      and professional awareness about the issue of weight stigma and the importance of
      the further development of assessment and prevention strategies of weight stigma.

PMID- 29171077
TI  - Louisa May Alcott and Hospital Sketches: An innovative approach to gender and
      nursing professionalization.
AB  - AIM: To show the development of an emerging nursing profession through the eyes
      of Louisa May Alcott and Hospital Sketches. BACKGROUND: In Hospital Sketches,
      Louisa May Alcott recounts her experiences when she worked as a nurse of injured
      soldiers during the American Civil War, in an autobiographically and masked
      referential way, which allows her to negotiate between transgression and
      convention. Unlike other reviews, in this paper the relevance of nursing remains
      highlighted. DESIGN: Discussion paper. DATA SOURCES: Existing literature in
      databases, history books and our own reading of facts. IMPLICATIONS FOR NURSING:
      Illuminating overlooked meanings hidden in nurses' personal sources enables to
      approach their contribution to history, improve their visibility and project the
      future of nursing. Nursing care, whether domestic or professional, was and
      remains a catalyst for change. CONCLUSION: Through Alcott's words, we understand
      the transition of nursing care as a gradual extension of the middle-class woman's
      domestic role and a progressive definition of nurses' identity. In particular, we
      highlight how certain professional nursing nuances which appear in the text are
      compatible with the gradual extension of the boundaries of women's domesticity.
      Furthermore, Alcott's use of literary devices reveals the delicate balance
      between women's domestic role and some new nursing professional features, which
      anticipates nursing professionalization.

PMID- 29171078
TI  - Men across a range of ethnicities have a higher prevalence of diabetes: findings
      from a cross-sectional study of 500 000 UK Biobank participants.
AB  - AIMS: Studies show that white men have a higher prevalence of Type 2 diabetes
      mellitus than women at a given age and BMI, but equivalent standardized data for
      other ethnic groups in the UK are sparse. METHODS: This cross-sectional study
      analysed UK Biobank data from 489 079 participants to compare the prevalence of
      diabetes mellitus across four major ethnic groups including: 471 700 (96.4%)
      white, 7871 (1.6%) South Asian, 7974 (1.6%) black and 1534 (0.3%) Chinese
      participants, before and after standardizing for age, socio-economic status
      (SES), BMI and lifestyle factors including physical activity, TV viewing, fruit
      and vegetable intake, processed meat, red meat, oily fish, alcohol intake and
      smoking. A subgroup analysis of South Asians was also undertaken. RESULTS: Crude
      diabetes prevalence was higher in men across all four ethnicities. After
      standardizing for age, SES, BMI and lifestyle factors, a significant sex
      difference in diabetes prevalence persisted in white (men 6.0% vs. women 3.6%),
      South Asian (21.0% vs. 13.8%) and black individuals (13.3% vs. 9.7%) (P <
      0.0001); there was a non-significant difference between Chinese men and women
      (7.1% vs. 5.5%) (P = 0.211). Sex differences persisted across South Asian
      subgroups. CONCLUSIONS: Men across a range of major ethnic groups including
      white, South Asian and black, have a higher prevalence of diabetes compared with
      women of similar age, BMI, SES and lifestyle in the UK.

PMID- 29171079
TI  - A survey of staffing levels in paediatric diabetes services throughout the UK.
AB  - AIMS: To assess staffing levels of healthcare professionals involved in the care
      of children and young people with diabetes in the UK. METHODS: A web-based
      questionnaire was distributed to lead consultant paediatricians from all
      paediatric diabetes services in the UK between October and December 2014. Data on
      staffing levels and other aspects of diabetes services were collected and
      differences between the four nations of the UK and across the 10 English diabetes
      networks were explored. RESULTS: Some 175 services (93%) caring for 29 711
      children and young people aged <= 24 years with diabetes participated in the
      survey. Northern Ireland and Wales had the lowest ratio of total staff to patient
      population. Nursing caseloads per one whole-time equivalent (WTE) nurse ranged
      from 71 patients in England to 110 patients in Northern Ireland with only 52% of
      the UK services meeting the Royal College of Nursing recommended nurse-to-patient
      ratio of > 1 : 70. Scotland and Northern Ireland had the highest ratio of
      consultants and fully trained doctors per 1000 patients (3.5 WTE). Overall, 17%
      of consultants had a Certificate of Completion of Training in Endocrinology and
      Diabetes. Some 44% of dietitians were able to adjust insulin dose. Only 43% of
      services provided 24-h access to advice from the diabetes team and 82% of
      services had access to a psychologist. Staffing levels adjusted for volume were
      not directly related to glycaemic performance of services in England and Wales.
      CONCLUSIONS: Wide variations in staffing levels existed across the four nations
      of the UK and important gaps were present in key areas.

PMID- 29171080
TI  - Testosterone therapy for sexual dysfunction in men with Type 2 diabetes: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - AIM: To evaluate the effectiveness of testosterone therapy on a range of sexual
      function domains in men with Type 2 diabetes. METHOD: Electronic databases were
      searched for studies investigating the effect of testosterone therapy on sexual
      function in men with Type 2 diabetes. All randomized controlled trials were
      considered for inclusion if they compared the efficacy of testosterone therapy
      with that of placebo and reported sexual function outcomes. Statistical analysis
      was performed using a random-effects model, and heterogeneity was expressed using
      the I2 statistic. RESULTS: A total of 611 articles were screened. Six randomized
      control trials, in a total of 587 men with Type 2 diabetes, were eligible for
      inclusion. The pooled data suggested that testosterone therapy improves sexual
      desire (random-effects pooled effect size 0.314; 95% CI 0.082-0.546) and erectile
      function (random-effects pooled effect size 0.203; 95% CI 0.007-0.399) when
      compared with control groups. Testosterone therapy had no significant effect on
      constitutional symptoms or other sexual domains compared with control groups. No
      studies have investigated the incidence of prostate cancer, fertility and
      cardiovascular disease after testosterone therapy in men with Type 2 diabetes.
      CONCLUSION: Testosterone therapy may moderately improve sexual desire and
      erectile function in men with Type 2 diabetes; however, available data are
      limited, and the long-term risks of testosterone therapy are not known in this
      specific patient group. We conclude that testosterone therapy is a potential
      treatment for men with Type 2 diabetes non-responsive to phosphodiesterase-5
      inhibitors. Testosterone therapy could be considered for men with Type 2 diabetes
      when potential risks and benefits of therapy are carefully considered and other
      therapeutic options are unsuitable.

PMID- 29171081
TI  - In vitro determination of Mexican Mestizo hair shaft diameter using optical
      coherence tomography.
AB  - BACKGROUND: Mexican mestizo population has a pluriethnic mixture of Amerindian,
      European and African ancestry, predominant in most Latin American countries.
      Until now, there are no reports about hair characteristics in this population,
      necessary to define normal values, for hair diseases evaluation and comparison
      among other ethnic groups. METHODS: The VivoSight(r) swept-source multibeam
      optical coherence tomography system was used to evaluate hair diameter and shape
      in 30 females. Three hair samples from each volunteer were measured transversely
      along three distances, generating nine cross-sectional images, two measurements
      per image and 18 measurements per patient for a total of 540 diameter
      measurements. RESULTS: Minimum hair diameter (n = 540) was 0.06 mm while maximum
      was 0.14 mm. Mean diameter was 0.10 +/- 0.01 mm as compared with Asian hair,
      which ranges from 0.08 mm to 0.12 mm. On morphological analysis, Mexican Mestizo
      hair tends to have a round shape with homogenous diameters, resembling Caucasian
      and Asian hair. CONCLUSION: Mexican hair is similar to Asian hair in diameter and
      shape and can be classified as 'thick' hair, which make it more resistant and
      with more volume. Cosmetic products intended to improve hair care in this
      population must to consider this characteristic.

PMID- 29171082
TI  - Mentor judgements and decision-making in the assessment of student nurse
      competence in practice: A mixed-methods study.
AB  - AIM: To investigate how mentors form judgements and reach summative assessment
      decisions regarding student competence in practice. BACKGROUND: Competence
      assessment is a significant component of pre-registration nursing programmes in
      the United Kingdom. Concerns exist that assessments are subjective, lack
      consistency and that mentors fail to judge student performance as unsatisfactory.
      DESIGN: A two-stage sequential embedded mixed-methods design. Data collected 2012
      2013. METHODS: This study involved a whole student cohort completing a UK
      undergraduate adult nursing programme (N = 41). Stage 1: quantitative data on
      mentor conduct of assessment interviews and the final decision recorded (N = 330
      from 270 mentors) were extracted from student Practice Assessment Documents
      (PADs). Stage 2: mentor feedback in student PADs was used in Stimulated Recall
      interviews with a purposive sample of final placement mentors (N = 17). These
      were thematically analysed. Findings were integrated to develop a theoretically
      driven model of mentor decision-making. RESULTS: Course assessment strategies and
      documentation had limited effect in framing mentor judgements and decisions.
      Rather, mentors amassed impressions, moderated by expectations of an "idealized
      student" by practice area and programme stage that influenced their management
      and outcome of the assessment process. These impressions were accumulated and
      combined into judgements that informed the final decision. This process can best
      be understood and conceptualized through the Brunswik's lens model of social
      judgement. CONCLUSION: Mentor decisions were reasoned and there was a shared
      understanding of judgement criteria and their importance. This impression-based
      nature of mentor decision-making questions the reliability and validity of
      competency-based assessments used in nursing pre-registration programmes.

PMID- 29171083
TI  - Blood Flow Changes in Subsynovial Connective Tissue on Contrast-Enhanced
      Ultrasonography in Patients With Carpal Tunnel Syndrome Before and After Surgical
      Decompression.
AB  - OBJECTIVES: Although qualitative alteration of the subsynovial connective tissue
      in the carpal tunnel is considered to be one of the most important factors in the
      pathophysiologic mechanisms of carpal tunnel syndrome (CTS), little information
      is available about the microcirculation in the subsynovial connective tissue in
      patients with CTS. The aims of this study were to use contrast-enhanced
      ultrasonography (US) to evaluate blood flow in the subsynovial connective tissue
      proximal to the carpal tunnel in patients with CTS before and after carpal tunnel
      release. METHODS: The study included 15 volunteers and 12 patients with CTS. The
      blood flow in the subsynovial connective tissue and the median nerve was
      evaluated preoperatively and at 1, 2, and 3 months postoperatively using contrast
      enhanced US. RESULTS: The blood flow in the subsynovial connective tissue was
      higher in the patients with CTS than in the volunteers. In the patients with CTS,
      there was a significant correlation between the blood flow in the subsynovial
      connective tissue and the median nerve (P = .01). The blood flow in both the
      subsynovial connective tissue and the median nerve increased markedly after
      carpal tunnel release. CONCLUSIONS: Our results suggest that increased blood flow
      in the subsynovial connective tissue may play a role in the alteration of the
      microcirculation within the median nerve related to the pathophysiologic
      mechanisms of CTS. The increase in the blood flow in the subsynovial connective
      tissue during the early postoperative period may contribute to the changes in
      intraneural circulation, and these changes may lead to neural recovery.

PMID- 29171084
TI  - Emerging adulthood and Type 1 diabetes: insights from the DAWN2 Study.
AB  - AIMS: To compare clinical, psychological, education and social variables in
      emerging adults (aged 18-30 years) with Type 1 diabetes with their adult
      counterparts aged >30 years. METHODS: A single assessment multinational sample
      was surveyed as part of the larger second Diabetes Attitudes, Wishes and Needs
      (DAWN2) study. Participants completed a series of surveys incorporating
      demographic as well as clinical questions (comorbidities, hypoglycaemia) and
      validated self-report scales concerning psychosocial (health impact, quality of
      life, beliefs and attitudes, self-management behaviours, healthcare experience
      and family support) and diabetes education factors. RESULTS: Emerging adults
      differed from adults aged >30 years with regard to a number of psychosocial
      variables. Emerging adults reported better overall quality of life, social
      support and support from their healthcare team compared with adults aged >30
      years of age; however, emerging adults experienced greater diabetes-specific
      distress and were less engaged in self-management. Diabetes education was related
      to a number of indicators, while experience of discrimination was harmful, but
      these impacts did not differ between emerging adults and adults aged >30 years.
      An analysis of geographical regions suggested that emerging adults in North
      America and Europe had better well-being than older adults, while the opposite
      was observed in Asia. CONCLUSIONS: Emerging adults, particularly those in the
      later phase (ages 25-30 years) are especially at risk in terms of diabetes
      specific distress. There is a need for novel interventions to meet the needs of
      these vulnerable emerging adults more effectively.

PMID- 29171087
TI  - Editorial Comment from Dr Yoshimura to Demographics, management and treatment
      outcomes of benign and malignant retroperitoneal tumors in Japan.

PMID- 29171085
TI  - Contrast-Enhanced Ultrasound Examination for the Assessment of Renal Perfusion in
      Cats with Chronic Kidney Disease.
AB  - BACKGROUND: Contrast-enhanced ultrasound examination (CEUS) is a functional
      imaging technique allowing noninvasive assessment of tissue perfusion. Studies in
      humans show that the technique holds great potential to be used in the diagnosis
      of chronic kidney disease (CKD). However, data in veterinary medicine are
      currently lacking. OBJECTIVES: To evaluate renal perfusion using CEUS in cats
      with CKD. ANIMALS: Fourteen client-owned cats with CKD and 43 healthy control
      cats. METHODS: Prospective case-controlled clinical trial using CEUS to evaluate
      renal perfusion in cats with CKD compared to healthy control cats. Time-intensity
      curves were created, and perfusion parameters were calculated using off-line
      software. A linear mixed model was used to examine differences between perfusion
      parameters of cats with CKD and healthy cats. RESULTS: In cats with CKD, longer
      time to peak and shorter mean transit times were observed for the renal cortex.
      In contrast, a shorter time to peak and rise time were seen for the renal
      medulla. The findings for the renal cortex indicate decreased blood velocity and
      shorter total duration of enhancement, likely caused by increased vascular
      resistance in CKD. Increased blood velocity in the renal medulla has not been
      described before and may be because of a different response to regulatory factors
      in cortex and medulla. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrast-enhanced
      ultrasound examination was capable of detecting perfusion changes in cats with
      CKD. Further research is warranted to assess the diagnostic capabilities of CEUS
      in early stage of the disease process.

PMID- 29171086
TI  - A randomized study of prourokinase during primary percutaneous coronary
      intervention in acute ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: To evaluate the efficacy and safety of intracoronary administration
      of prourokinase via balloon catheter during primary percutaneous coronary
      interventions (PCI) in patients with acute ST-segment elevation myocardial
      infarction (STEMI). METHODS: Acute STEMI patients underwent primary PCI were
      randomly divided into two groups: intracoronary prourokinase (IP) group (n = 118)
      and control group (n = 112). During primary PCI, prourokinase or saline were
      injected to the distal end of the culprit lesion via balloon catheter after
      balloon catheter dilatation. Demographic and clinical characteristics, infarct
      size, myocardial reperfusion, and cardiac functions were evaluated and compared
      between two groups. Hemorrhagic complications and MACE occurred in the 6-months
      follow up were recorded. RESULTS: No significant differences were observed
      between two groups with respect to baseline demographic, clinical, and
      angiographic characteristics (P > 0.05). In IP group, more patients had complete
      ST segment resolution (>70%) compared with control group (P < 0.05). Patients in
      IP group showed lower levels of serum CK, CK-MB and TnI, and a much higher
      myocardial blood flow (MBF) than those in control group (P < 0.05). No
      significant differences of TIMI major or minor bleeding complications were
      observed between the two groups (P > 0.05). At 6-months follow-up, there was a
      trend that patients in the IP group had a less chance to have MACE, though it was
      not statistically different (8.5% vs 12.5%, P > 0.05). CONCLUSIONS: Intracoronary
      administration of prourokinase via balloon catheter during primary PCI
      effectively improved myocardial perfusion in STEMI patients.

PMID- 29171088
TI  - Comparison of Single, Averaged, and Pooled Urine Protein:Creatinine Ratios in
      Proteinuric Dogs Undergoing Medical Treatment.
AB  - BACKGROUND: Monitoring urine protein:creatinine ratios (UPC) in dogs with protein
      losing nephropathy (PLN) is challenging because of day-to-day variation in UPC
      results. HYPOTHESIS/OBJECTIVES: Determine whether single, averaged, or pooled
      samples from PLN dogs receiving medical treatment yield comparable UPCs,
      regardless of degree of proteinuria. ANIMALS: Twenty-five client-owned PLN dogs
      receiving medical treatment. METHODS: UPC ratios were prospectively measured in
      each dog utilizing 3 methods: single in-hospital sample (day 3), average sample
      (days 1-3), and pooled sample (equal pooling of urine from days 1-3). Bland
      Altman analysis was performed to evaluate agreement between methods for all dogs,
      as well as in subgroups of dogs (UPC <=4 or UPC >4). RESULTS: For all dogs, Bland
      Altman log-transformed 95% limits of agreement were -0.07-0.18 (single versus
      pooled UPC), -0.06-0.16 (single versus average UPC), and -0.06-0.04 (pooled
      versus average UPC). For dogs with UPC <=4, Bland-Altman 95% limits of agreement
      were -0.42-0.82 (single versus pooled UPC), -0.38-0.76 (single versus average
      UPC), and -0.27-0.25 (pooled versus average UPC). For dogs with UPC >4, Bland
      Altman 95% limits of agreement were -0.17-2.4 (single versus pooled UPC), -0.40
      2.2 (single versus average UPC), and -0.85-0.43 (pooled versus average UPC).
      CONCLUSIONS AND CLINICAL IMPORTANCE: UPC ratios from all methods were comparable
      in PLN dogs receiving medical treatment. In PLN dogs with UPC >4, more
      variability between methods exists likely because of higher in-hospital results,
      but whether this finding is clinically relevant is unknown.

PMID- 29171089
TI  - Significance of total colonoscopy screening before definitive radiotherapy for
      prostate cancer on the detection of anorectocolonic disease requiring
      intervention in advance.

PMID- 29171091
TI  - Internal fit of three-unit fixed dental prostheses produced by computer-aided
      design/computer-aided manufacturing and the lost-wax metal casting technique
      assessed using the triple-scan protocol.
AB  - Suboptimal adaptation of fixed dental prostheses (FDPs) can lead to technical and
      biological complications. It is unclear if the computer-aided design/computer
      aided manufacturing (CAD/CAM) technique improves adaptation of FDPs compared with
      FDPs made using the lost-wax and metal casting technique. Three-unit FDPs were
      manufactured by CAD/CAM based on digital impression of a typodont model. The FDPs
      were made from one of five materials: pre-sintered zirconium dioxide; hot
      isostatic pressed zirconium dioxide; lithium disilicate glass-ceramic; milled
      cobalt-chromium; and laser-sintered cobalt-chromium. The FDPs made using the lost
      wax and metal casting technique were used as reference. The fit of the FDPs was
      analysed using the triple-scan method. The fit was evaluated for both single
      abutments and three-unit FDPs. The average cement space varied between 50 MUm and
      300 MUm. Insignificant differences in internal fit were observed between the
      CAD/CAM-manufactured FDPs, and none of the FPDs had cement spaces that were
      statistically significantly different from those of the reference FDP. For all
      FDPs, the cement space at a marginal band 0.5-1.0 mm from the preparation margin
      was less than 100 MUm. The milled cobalt-chromium FDP had the closest fit. The
      cement space of FDPs produced using the CAD/CAM technique was similar to that of
      FDPs produced using the conventional lost-wax and metal casting technique.

PMID- 29171090
TI  - 24-Hour Kinetics of Cardiac Troponin-T Using a "High-Sensitivity" Assay in
      Thoroughbred Chuckwagon Racing Geldings after Race and Associated Clinical
      Sampling Guidelines.
AB  - BACKGROUND: A "high-sensitivity" cardiac troponin-T (hscTnT) assay recently has
      been validated for use in horses and is a specific biomarker of myocardial
      damage. Postexercise release kinetics of cTnT utilizing the hscTnT assay have yet
      to be established in horses. OBJECTIVES: To determine: (1) cTnT release kinetics
      in racing Thoroughbreds after a high-intensity 5/8th mile Chuckwagon race; (2)
      the effects of age on pre- and postrace cTnT concentrations; and (3) sampling
      guidelines for clinicians evaluating horses presenting after exercise. ANIMALS:
      Samples were obtained from 38 Thoroughbred geldings aged 5-16 years before racing
      and immediately, 2, 3, 4, 6, 12, and 24 hour postrace. METHODS: Prospective,
      observational study with convenience sampling. A fifth-generation hscTnT assay
      was used for plasma sample analysis, and concentrations were compared at all time
      points. Correlations were determined between cTnT concentrations and age.
      Biochemistry analysis was performed to assess rhabdomyolysis, renal failure, and
      exercise-induced dehydration. RESULTS: All horses with measureable cTnT
      concentrations had significant postexercise increases in cTnT with a median peak
      (8.0 ng/L) at 3-hour postrace. All horses had peak postexercise cTnT
      concentrations 2- to 6-hour postrace <= the 99th percentile upper reference limit
      of 23.2 ng/L, after which all cTnT concentrations decreased until returning to
      baseline by 12-24 hours. There was no correlation over time between cTnT
      concentrations and age. CONCLUSIONS AND CLINICAL IMPORTANCE: In racing
      Thoroughbreds completing short-duration, high-intensity Chuckwagon races, cTnT
      concentrations are expected to be increased 2- to 6-hour postrace and to decrease
      by 12-24 hours while remaining <=23.2 ng/L throughout. This study contributes to
      establishing guidelines for clinical use of the hscTnT assay in exercising
      horses.

PMID- 29171092
TI  - Oral keratinocytes synthesize CTACK: A new insight into the pathophysiology of
      the oral mucosa.
AB  - The skin-associated chemokine CTACK plays a key role in many inflammatory
      conditions and could be instrumental in the pathophysiology of tissue-specific
      immunological diseases such as oral lichen planus (OLP). In this study, we
      investigated, by RT-PCR, ELISA, chemotaxis assays, and fluorescence-activated
      cell sorting (FACS), the production of CTACK in oral keratinocytes, its
      expression in tissues from normal and OLP patients, and its role in T-cell
      recruitment.CTACK was produced by the oral epithelium, and it affects chemotaxis
      of memory CLA+ cells to the oral epithelium. CTACK mRNA was expressed
      constitutively in primary oral epithelium and was increased during pro
      inflammatory IFN-gamma treatment. We found a constitutive production of CTACK at
      a protein level in oral primary cells that increased after IFN-gamma treatment.
      Moreover, we confirmed that CTACK attracts memory T cells and those T cells that
      express CLA above the level of basal migration.

PMID- 29171093
TI  - Government helper and citizen advocate? A case study of the multiple roles and
      pressures facing a nongovernmental organization contracted by government to
      strengthen community health in northern India.
AB  - While nongovernmental organizations (NGOs) can potentially strengthen valuable
      citizen political engagement, NGOs that are increasingly oriented towards donor
      and government contracts may instead contribute to depoliticizing development.
      Amidst competing pressures, NGO experiences and agency in managing multiple roles
      require examination. We present a qualitative case study of an NGO implementing a
      government-designed intervention to strengthen Village Health, Sanitation, and
      Nutrition Committees (VHSNCs) in rural north India. Despite a challenging context
      of community scepticism and poor government services, the NGO did successfully
      form VHSNCs by harnessing its respected interlocutor status, preexisting
      relationships, and ability to "sell" the VHSNC as a mechanism for improving local
      well-being. While the VHSNC enabled community members to voice concerns to
      government officials, improvements often failed to meet community expectations.
      NGO staff endured community frustration on one hand and rebuffs from lower-level
      officials on the other, while feeling undersupported by the government contract.
      Consequently, although contracted to strengthen a community institution, the NGO
      increasingly worked alongside VHSNC members to try to strengthen the public
      sector. Contrary to assumptions that NGOs become "tamed" through taking
      government contracts, being contracted to deliver inputs for community
      participation was intertwined with microlevel political action, though this came
      at a cost to the NGO.

PMID- 29171094
TI  - PERV inactivation is necessary to guarantee absence of pig-to-patient PERVs
      transmission in xenotransplantation.

PMID- 29171096
TI  - Risk of acute myocardial infarction with real-world NSAIDs depends on dose and
      timing of exposure.
AB  - PURPOSE: Real-life use of nonsteroidal anti-inflammatory drugs (NSAIDs) is
      dynamic. This study aimed to characterize the temporal association between time
      varying NSAID exposure and acute myocardial infarction (MI). METHODS: Nested case
      control analyses were conducted on a Quebec administrative health cohort. NSAID
      dose, confounders, and outcome status were determined for each day of follow-up.
      To better account for dose and timing of past exposures, flexible weighted
      cumulative exposure models were also fitted. RESULTS: The cohort consisted of 233
      816 older adults including 21 256 acute MI cases. Dose-related increased risks of
      MI were found with current use of all NSAIDs. In models not accounting for
      duration of use, ORs (95%CI) for the most common current daily dose vs. no
      current exposure were: celecoxib 200 mg: 1.16 (1.10, 1.22), diclofenac 150 mg:
      1.59 (1.38, 1.84), ibuprofen 1200 mg: 1.42 (1.17, 1.74), naproxen 750 mg: 1.38
      (1.21, 1.58), and rofecoxib 25 mg: 1.54 (1.43, 1.66). Weighted cumulative
      exposure models confirmed that all NSAIDs-including naproxen-are associated with
      an increased risk of MI and suggested that doses taken up to 3 weeks ago for
      rofecoxib, ibuprofen, and naproxen and up to 75 days ago for diclofenac and
      celecoxib may contribute to the current MI risk. However, the celecoxib risk
      seems to require continuous use for more than 30 days, whereas for other NSAIDs,
      a heightened MI risk occurs within 7 days. CONCLUSIONS: Weighted cumulative
      exposure analysis uncovered NSAID-specific differences in the immediate MI risk
      and how this risk seems to accumulate. KEY POINTS Accurate assessment of drug
      safety requires an etiologically correct model encompassing all relevant aspects
      of exposure. Weighted cumulative exposure models suggest that the relative
      importance of past doses on the risk of MI differs among NSAIDs. All common
      NSAIDs are associated with an increased MI risk. Celecoxib MI risk seems to
      depend on continuously using the drug for more than 30 days, whereas for
      ibuprofen, rofecoxib, diclofenac, and naproxen, a heightened MI risk occurs
      within 7 days of use.

PMID- 29171097
TI  - Usefulness of left ventricular strain analysis in patients with takotsubo
      syndrome during acute phase.
AB  - BACKGROUND: Takotsubo syndrome (TTS) is peculiar clinical condition often
      resembling an acute coronary syndrome and mostly affecting postmenopausal women
      after a stressful trigger. TTS was initially thought to be a relatively benign
      condition. However, current data have shown it may be associated with
      considerable inpatient morbidity and carry a small, but important, mortality
      risk. METHODS: We hypothesized that left ventricular (LV) regional and global
      longitudinal strain (GLS) assessed with 2D speckle tracking echocardiography
      could identify early systolic functional impairment and predict in-hospital
      cardiovascular events. We conducted a retrospective descriptive study reviewing
      patients with the discharge diagnosis of TCM between 2003 and 2016 at our
      institution. RESULTS: One hundred patients with TSS met the Modified Mayo Clinic
      criteria. Using 2D speckle tracking echocardiography, two independent
      cardiologists assessed the LV GLS as well as the longitudinal strain (LS) of 7
      individual segments [basal-septal (BS); mid-septal (MS), apical-septal (AS),
      apex, basal-lateral (BL), mid-lateral (ML), and apical-lateral (AL)]. The inter
      observer variability was <5%. Mean age was 69.1 years, 87% were females, and 53%
      were African Americans. Mean initial LV EF was 32% +/- 9.8%. In univariate
      analysis, patients with worse BL, ML, and GLS profiles (means: -5.7; -3.3, and 
      4, respectively) had higher in-hospital mortality (P < .05). Worse BL and ML
      profiles (means: -8.6 and -7.3, respectively) were associated with higher
      prevalence of MACE (major adverse cardiovascular outcomes) (P < .05). In a
      multivariate analysis, mid-lateral strain >= -7 and basolateral strain >= -10
      were independent predictors of in-hospital mortality and MACE + in-hospital heart
      failure, respectively. CONCLUSIONS: Assessment of LV global and segmental
      longitudinal strain by speckle tracking has important prognostic value in the
      acute phase of TTS. Additional large-scale studies will be needed to confirm our
      findings.

PMID- 29171098
TI  - Can bladder preservation therapy come to the center stage?
AB  - Decision-making in urological cancer care requires a multidisciplinary approach
      for refinement, but its impact on urothelial carcinoma of the bladder has not
      been fully addressed for the past three decades, except for the latest
      immunological checkpoint inhibitor approved by the U.S. Food and Drug
      Administration for metastatic muscle-invasive bladder cancer that is resistant to
      platinum-based chemotherapy. For the time being, radical cystectomy is the gold
      standard of curative therapy for muscle-invasive bladder cancer. Trimodal therapy
      that combines chemotherapy for the purpose of radiation sensitization, external
      beam radiotherapy and transurethral resection of bladder tumor has emerged as a
      potential alternative treatment option that preserves the bladder. In lack of
      randomized studies for bladder preservation therapy compared with surgery, the
      principles of management of urothelial carcinoma of the bladder have evolved in
      recent times, with an emphasis on bladder preservation. A number of bladder
      preservation techniques are available to the surgeon; however, appropriately
      selected patients with muscle-invasive bladder cancer should be offered the
      opportunity to discuss various treatment options, including organ-sparing
      trimodal therapy. The aim of the present study was to compare the primary
      outcomes of the available treatment methods and identify the sources of variance
      among studies. A review of various bladder preservation techniques in vogue for
      the management of urothelial carcinoma of the bladder is discussed.

PMID- 29171095
TI  - The Gastrointestinal Microbiome: A Review.
AB  - The gastrointestinal microbiome is a diverse consortium of bacteria, archaea,
      fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in
      humans and other mammals have implicated the microbiome in a range of physiologic
      processes that are vital to host health including energy homeostasis, metabolism,
      gut epithelial health, immunologic activity, and neurobehavioral development. The
      microbial genome confers metabolic capabilities exceeding those of the host
      organism alone, making the gut microbiome an active participant in host
      physiology. Recent advances in DNA sequencing technology and computational
      biology have revolutionized the field of microbiomics, permitting mechanistic
      evaluation of the relationships between an animal and its microbial symbionts.
      Changes in the gastrointestinal microbiome are associated with diseases in humans
      and animals including inflammatory bowel disease, asthma, obesity, metabolic
      syndrome, cardiovascular disease, immune-mediated conditions, and
      neurodevelopmental conditions such as autism spectrum disorder. While there
      remains a paucity of data regarding the intestinal microbiome in small animals,
      recent studies have helped to characterize its role in host animal health and
      associated disease states. This review is intended to familiarize small animal
      veterinarians with recent advances in the field of microbiomics and to prime them
      for a future in which diagnostic tests and therapies will incorporate these
      developments into clinical practice.

PMID- 29171099
TI  - Regional Citrate Anticoagulation for Intermittent Hemodialysis in Dogs.
AB  - BACKGROUND: The traditional systemic heparinization used for anticoagulation in
      extracorporeal therapies may cause fatal complications in animals at risk of
      bleeding. HYPOTHESIS/OBJECTIVES: To develop and validate a protocol of regional
      citrate anticoagulation (RCA) for intermittent hemodialysis in dogs. ANIMALS: A
      total of 172 dogs treated with hemodialysis for acute kidney injury. METHODS: In
      vitro titration was performed, adding trisodium citrate and calcium chloride to
      heparinized canine blood. A tentative protocol was used first in 66 treatments
      with additional heparinization and subsequently in 518 heparin-free treatments.
      Safety and adequacy of RCA were assessed based on clinical and laboratory
      monitoring, dialyzer pressure gradient, treatment completion, and visual scoring
      of the extracorporeal circuit. RESULTS: Addition of 1 mmol/L citrate to
      heparinized blood decreased the ionized calcium concentration by 0.23 mmol/L (95%
      confidence interval [CI], 0.16-0.30) and 1 mmol/L calcium increased it by 0.62
      mmol/L (95% CI, 0.45-0.79). Heparin-free treatments were initiated with infusion
      of trisodium citrate (102 mmol/L) at 2.55 mmol/L blood and calcium chloride (340
      mmol/L) at 0.85 mmol/L. Citrate and calcium administrations were adjusted in 27
      and 34% of the treatments, respectively. Overall, anticoagulation was
      satisfactory in 92% of the treatments, with expected azotemia reduction in 95%
      (urea) and 86% (creatinine), stable dialyzer pressure gradient in 82%, and clean
      extracorporeal circuits in 92% of the treatments. Eighteen treatments (3.5%) were
      discontinued prematurely, 9 because of clotting and 9 for reasons unrelated to
      the RCA procedure. CONCLUSIONS AND CLINICAL IMPORTANCE: Regional citrate
      anticoagulation allows safe and efficient heparin-free hemodialysis in dogs at
      risk of bleeding.

PMID- 29171100
TI  - Impact of age-related macular degeneration on object searches in realistic
      panoramic scenes.
AB  - BACKGROUND: This study investigated whether realistic immersive conditions with
      dynamic indoor scenes presented on a large, hemispheric panoramic screen covering
      180 degrees  of the visual field improved the visual search abilities of
      participants with age-related macular degeneration (AMD). METHOD: Twenty-one
      participants with AMD, 16 age-matched controls and 16 young observers were
      included. Realistic indoor scenes were presented on a panoramic five metre
      diameter screen. Twelve different objects were used as targets. The participants
      were asked to search for a target object, shown on paper before each trial,
      within a room composed of various objects. A joystick was used for navigation
      within the scene views. A target object was present in 24 trials and absent in 24
      trials. The percentage of correct detection of the target, the percentage of
      false alarms (that is, the detection of the target when it was absent), the
      number of scene views explored and the search time were measured. RESULTS: The
      search time was slower for participants with AMD than for the age-matched
      controls, who in turn were slower than the young participants. The participants
      with AMD were able to accomplish the task with a performance of 75 per cent
      correct detections. This was slightly lower than older controls (79.2 per cent)
      while young controls were at ceiling (91.7 per cent). Errors were mainly due to
      false alarms resulting from confusion between the target object and another
      object present in the scene in the target-absent trials. CONCLUSION: The outcomes
      of the present study indicate that, under realistic conditions, although slower
      than age-matched, normally sighted controls, participants with AMD were able to
      accomplish visual searches of objects with high accuracy.

PMID- 29171101
TI  - In vitro Inhibition of Canine Complement-Mediated Hemolysis.
AB  - BACKGROUND: Immune-mediated hemolytic anemia (IMHA) is the most common
      hematologic immune-mediated disease in dogs. Complement fixation on erythrocytes
      causes hemolysis. Complement inhibition decreases hemolysis in people with the
      hemolytic disease and also may prove effective in treating IMHA in dogs.
      HYPOTHESIS/OBJECTIVES: Evaluate the in vitro efficacy of 2 complement inhibitors
      used in humans against canine complement. METHODS: The inhibitory activity of the
      C3-inhibitor compstatin and recombinant human C1-esterase inhibitor (C1-INH) was
      evaluated using an in vitro hemolytic assay and spectrophotometric measurement of
      released hemoglobin. Dose-response curves for each inhibitor were generated.
      RESULTS: Compstatin decreased approximately 50% of canine complement-mediated
      hemolysis in initial experiments. This inhibition largely was lost when a new lot
      of drug was purchased. C1-INH showed a dose-dependent inhibition. The highest
      concentration of C1-INH tested (500 MUg/mL) decreased >80% of canine complement
      mediated hemolysis, and the lowest concentration tested (31.25 MUg/mL) decreased
      hemolysis >60%. CONCLUSIONS AND CLINICAL IMPORTANCE: Human C1-INH is a robust
      inhibitor of canine complement-mediated hemolysis, whereas compstatin was
      minimally and variably effective. Human C1-INH may substantially decrease
      complement-mediated hemolysis in dogs with IMHA and warrants further
      investigation.

PMID- 29171102
TI  - Comments on manuscript: Lidocaine for pain control during intrauterine device
      insertion.

PMID- 29171104
TI  - Elevated perseveration errors on a verbal fluency task in frequent nightmare
      recallers: a replication.
AB  - A recent study reported that individuals recalling frequent idiopathic nightmares
      (NM) produced more perseveration errors on a verbal fluency task than did control
      participants (CTL), while not differing in overall verbal fluency. Elevated
      scores on perseveration errors, an index of executive dysfunction, suggest a
      cognitive inhibitory control deficit in NM participants. The present study sought
      to replicate these results using a French-speaking cohort and French language
      verbal fluency tasks. A phonetic verbal fluency task using three stimulus letters
      (P, R, V) and a semantic verbal fluency task using two stimulus categories
      (female and male French first names) were administered to 23 participants with
      frequent recall of NM (>=2 NM per week, mean age = 24.4 +/- 4.0 years), and to 16
      CTL participants with few recalled NM (<= 1 NM per month, mean age = 24.5 +/- 3.8
      years). All participants were French-speaking since birth and self-declared to be
      in good mental and physical health apart from their NM. As expected, groups did
      not differ in overall verbal fluency, i.e. total number of correct words produced
      in response to stimulus letters or categories (P = 0.97). Furthermore, groups
      exhibited a difference in fluency perseveration errors, with the NM group having
      higher perseveration than the CTL group (P = 0.03, Cohen's d = 0.745). This
      replication suggests that frequent NM recallers have executive inhibitory
      dysfunction during a cognitive association task and supports a neurocognitive
      model which posits fronto-limbic impairment as a neural correlate of disturbed
      dreaming.

PMID- 29171103
TI  - Adult functions for the Drosophila DHR78 nuclear receptor.
AB  - BACKGROUND: The Testicular Receptors 2 and 4 (TR2, TR4) comprise a small
      subfamily of orphan nuclear receptors. Genetic studies in mouse models have
      identified roles for TR4 in developmental progression, fertility, brain
      development, and metabolism, as well as genetic redundancy with TR2. Here we
      study the adult functions of the single Drosophila member of this subfamily,
      DHR78, with the goal of defining its ancestral functions in the absence of
      genetic redundancy. RESULTS: We show that DHR78 mutants have a shortened
      lifespan, reduced motility, and mated DHR78 mutant females display a reduced
      feeding rate. Transcriptional profiling reveals a major role for DHR78 in
      promoting the expression of genes that are expressed in the midgut, suggesting
      that it contributes to nutrient uptake. We also identify roles for DHR78 in
      maintaining the expression of genes in the ecdysone and Notch signaling pathways.
      CONCLUSIONS: This study provides a new context for linking the molecular activity
      of the TR orphan nuclear receptors with their complex roles in adult physiology
      and lifespan. Developmental Dynamics 247:315-322, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29171105
TI  - Effects of a family-support programme for pregnant women with foetal
      abnormalities requiring pregnancy termination: A randomized controlled trial in
      China.
AB  - AIM: We examined the effects of a family-support programme for pregnant women
      with foetal abnormalities in terms of family support, depression, and post
      traumatic stress symptoms. METHOD: A randomized controlled trial was conducted
      from November 2016 to June 2017. A total of 124 pregnant women with foetal
      abnormalities were recruited and randomly assigned to the intervention group that
      received a family-support programme or control group that received only routine
      care. Self-reported questionnaires including the Family Adaptation Partnership
      Growth Affection and Resolve Index, the Edinburgh Postnatal Depression Scale, and
      the Impact of Event Scale-Revised were administered before and after
      intervention. RESULTS: Relative to the control group, posttest Family Adaptation
      Partnership Growth Affection and Resolve Index scores and scores on the intimacy
      domain were significantly higher in the intervention group, the Edinburgh
      Postnatal Depression Scale and Impact of Event Scale-Revised scores and the
      scores on all subscales except the intrusion subscale were significantly lower in
      the intervention group. CONCLUSION: The findings of this study suggest that
      family-support programme represents an effective and feasible support approach of
      improving family support and reducing depression and post-traumatic stress
      symptoms for pregnant women with foetal abnormalities requiring pregnancy
      termination.

PMID- 29171106
TI  - Autophagy regulates cisplatin-induced stemness and chemoresistance via the
      upregulation of CD44, ABCB1 and ADAM17 in oral squamous cell carcinoma.
AB  - OBJECTIVE: We inspected the relevance of CD44, ABCB1 and ADAM17 in OSCC stemness
      and deciphered the role of autophagy/mitophagy in regulating stemness and
      chemoresistance. MATERIAL AND METHODS: A retrospective analysis of CD44, ABCB1
      and ADAM17 with respect to the various clinico-pathological factors and their
      correlation was analysed in sixty OSCC samples. Furthermore, the stemness and
      chemoresistance were studied in resistant oral cancer cells using sphere
      formation assay, flow cytometry and florescence microscopy. The role of
      autophagy/mitophagy was investigated by transient transfection of siATG14, GFP
      LC3, tF-LC3, mKeima-Red-Mito7 and Western blot analysis of autophagic and
      mitochondrial proteins. RESULTS: In OSCC, high CD44, ABCB1 and ADAM17 expressions
      were correlated with higher tumour grades and poor differentiation and show
      significant correlation in their co-expression. In vitro and OSCC tissue double
      labelling confirmed that CD44+ cells co-expresses ABCB1 and ADAM17. Further,
      cisplatin (CDDP)-resistant FaDu cells displayed stem-like features and higher
      CD44, ABCB1 and ADAM17 expression. Higher autophagic flux and mitophagy were
      observed in resistant FaDu cells as compared to parental cells, and inhibition of
      autophagy led to the decrease in stemness, restoration of mitochondrial proteins
      and reduced expression of CD44, ABCB1 and ADAM17. CONCLUSION: The CD44+ /ABCB1+
      /ADAM17+ expression in OSCC is associated with stemness and chemoresistance.
      Further, this study highlights the involvement of mitophagy in chemoresistance
      and autophagic regulation of stemness in OSCC.

PMID- 29171107
TI  - Assessing sleep quality using self-report and actigraphy in PTSD.
AB  - Sleep disturbance is commonly reported by participants with post-traumatic stress
      disorder, but objective evidence of poor sleep is often absent. Here we compared
      self-report and actigraphic evaluations of sleep between veterans with post
      traumatic stress disorder and controls. Participants reported their sleep
      retrospectively for the month before the recording night and on the recording
      night. On the recording night, they wore an Actiwatch-64 and were instructed to
      press the marker button upon getting into bed, each time they awoke, and at their
      final awakening. The post-traumatic stress disorder group reported much worse
      sleep than controls on the Pittsburgh Sleep Quality Index for the previous month
      and somewhat poorer sleep on the recording night. However, on the recording
      night, neither diary nor actigraphic measures of number of awakenings, total time
      in bed, nor time lying awake after sleep onset differed between participants with
      and without post-traumatic stress disorder. Diary-reported number of awakenings
      was fewer than actigraphically captured awakenings. These results suggest a
      memory bias towards remembering worse sleep on the nights before the recording
      night.

PMID- 29171108
TI  - Optimization and validation of automated hippocampal subfield segmentation across
      the lifespan.
AB  - Automated segmentation of hippocampal (HC) subfields from magnetic resonance
      imaging (MRI) is gaining popularity, but automated procedures that afford high
      speed and reproducibility have yet to be extensively validated against the
      standard, manual morphometry. We evaluated the concurrent validity of an
      automated method for hippocampal subfields segmentation (automated segmentation
      of hippocampal subfields, ASHS; Yushkevich et al., ) using a customized atlas of
      the HC body, with manual morphometry as a standard. We built a series of
      customized atlases comprising the entorhinal cortex (ERC) and subfields of the HC
      body from manually segmented images, and evaluated the correspondence of
      automated segmentations with manual morphometry. In samples with age ranges of 6
      24 and 62-79 years, 20 participants each, we obtained validity coefficients
      (intraclass correlations, ICC) and spatial overlap measures (dice similarity
      coefficient) that varied substantially across subfields. Anterior and posterior
      HC body evidenced the greatest discrepancies between automated and manual
      segmentations. Adding anterior and posterior slices for atlas creation and
      truncating automated output to the ranges manually defined by multiple
      neuroanatomical landmarks substantially improved the validity of automated
      segmentation, yielding ICC above 0.90 for all subfields and alleviating
      systematic bias. We cross-validated the developed atlas on an independent sample
      of 30 healthy adults (age 31-84) and obtained good to excellent agreement: ICC
      (2) = 0.70-0.92. Thus, with described customization steps implemented by experts
      trained in MRI neuroanatomy, ASHS shows excellent concurrent validity, and can
      become a promising method for studying age-related changes in HC subfield
      volumes.

PMID- 29171109
TI  - A systematic review of quantitative observational studies investigating
      psychological distress in testicular cancer survivors.
AB  - OBJECTIVE: Testicular cancer (TC) affects young men and may cause psychological
      distress despite a good prognosis. This systematic review evaluated the
      prevalence, severity, and correlates of anxiety, depression, fear of cancer
      recurrence (FCR), and distress in TC survivors. METHODS: A systematic search of
      literature published 1977 to 2017 was conducted to find quantitative studies
      including TC survivor-reported outcomes relevant to review objectives. The
      quality of included articles was assessed, and a narrative synthesis conducted.
      RESULTS: Of 6717 articles identified, 66 (39 good, 20 fair, and 7 poor quality)
      reporting results from 36 studies were included. Testicular cancer survivors'
      mean anxiety levels were higher than in the general population, while mean
      depression and distress were no different. Clinically significant anxiety (~1 in
      5) and to a lesser extent distress (~1 in 7), but not depression, were more
      prevalent in TC survivors than the general population. Approximately 1 in 3 TC
      survivors experienced elevated FCR. Poorer psychological outcomes were more
      common among TC survivors who were single, unemployed/low socio-economic status,
      suffering from co-morbidities, experiencing worse symptoms/side effects, and
      using passive coping strategies. CONCLUSIONS: Many TC survivors do not experience
      significant psychological morbidity, but anxiety and FCR are prevalent.
      Inadequate coping resources (eg, low socio-economic status and social support)
      and strategies (eg, avoidance) and greater symptoms/side effects were associated
      with poorer outcomes. Theoretically driven prospective studies would aid
      understanding of how outcomes change over time and how to screen for risk. Age
      and gender appropriate interventions that prevent and manage issues specific to
      TC survivors are also needed.

PMID- 29171110
TI  - The prevalence of narcolepsy in Catalunya (Spain).
AB  - Previous studies have estimated an overall prevalence for narcolepsy between 15
      and 70 cases per 100 000 inhabitants. We aimed to estimate the prevalence of
      narcolepsy in Catalunya (Catalonia), a north-east region of Spain (7 424 754
      inhabitants), on 31 December 2014 by identifying all living subjects diagnosed
      with narcolepsy. First, we identified patients diagnosed by one of the 13 sleep,
      paediatric or neurological departments that perform tests regularly to diagnose
      narcolepsy. In a second phase, we searched for additional patients with
      narcolepsy in a clinical database of the primary health-care system. Clinical
      files were reviewed and narcolepsy diagnosis validated according to the Brighton
      Collaboration case definitions. Three hundred and twenty-five patients had a
      validated diagnosis of narcolepsy in the specialized centres (mean age: 44.6
      years, range: 6-89; male: 60.3%; 85% with narcolepsy type 1), including 17.8%
      cases in Brighton, definition level 1, 62.5% in level 2, 15.4% in level 3 and
      4.3% in level 4a. The overall prevalence for narcolepsy was 4.4; 3.7 for
      narcolepsy type 1 and 0.7 cases per 100 000 inhabitants for narcolepsy type 2.
      Fifty-six additional narcoleptic patients were identified in the primary health
      care system, increasing the overall prevalence to 5.2 cases per 100 000
      inhabitants. Prevalence rates for narcolepsy type 1 increased from childhood to
      adulthood, but in subjects aged more than 50 years there was a substantial drop
      in prevalence rates, suggesting the presence of a significant pool of undiagnosed
      cases in this population. Narcolepsy can be considered a rare neurological
      disorder in Catalunya.

PMID- 29171111
TI  - Knockdown of ubiquitin D inhibits adipogenesis during the differentiation of
      porcine intramuscular and subcutaneous preadipocytes.
AB  - OBJECTIVES: Intramuscular fat (IMF) has a significant influence on porcine meat
      quality. Ubiquitin D (UBD) is involved in the management of diverse intracellular
      processes. However, its physiological functions in adipose cell differentiation
      and proliferation are still poorly defined. MATERIALS AND METHODS: Intramuscular
      and subcutaneous preadipocytes were isolated from the longissimus dorsi and neck
      subcutaneous deposits of Chinese native Guanzhong Black piglets (3-5 days old),
      respectively. Lentivirus with short hairpin RNA (shRNA) for UBD was applied to
      knockdown UBD expression. We used real-time PCR and Western blot analysis to
      detect gene expression. Lipid droplets were dyed with Oil Red O, and cell
      proliferation was assessed using flow cytometry, 5-ethynyl-2'-deoxyuridine
      incorporation and cell counting assays. RESULTS: Lipogenesis through the Akt/mTOR
      pathway was inhibited when preadipocytes were transfected with UBD shRNA. The
      expression of adipogenic genes and the number of lipid droplets were obviously
      diminished. Moreover, repression of UBD attenuated cell proliferation. UBD
      downregulation resulted in cell cycle arrest because of a decreased proportion of
      S-phase cells, and the expression of positive cell proliferation markers was
      significantly decreased. CONCLUSION: These observations illustrated that
      knockdown of UBD partially suppressed porcine intramuscular and subcutaneous
      preadipocyte adipogenesis through the Akt/mTOR signalling and inhibited cell
      proliferation, suggesting the essential role of UBD in the differentiation of
      preadipocytes.

PMID- 29171113
TI  - Excessive contact force can overcome irrigated tip catheter benefits during
      atrial fibrillation ablation.

PMID- 29171112
TI  - The impact of social deprivation on the response to a randomised controlled trial
      of a weight management intervention (BeWEL) for people at increased risk of
      colorectal cancer.
AB  - BACKGROUND: Although 45% of colorectal cancer (CRC) cases may be avoidable
      through appropriate lifestyle and weight management, health promotion
      interventions run the risk of widening health inequalities. The BeWEL randomised
      controlled trial assessed the impact of a diet and activity programme in
      overweight adults who were diagnosed with a colorectal adenoma, demonstrating a
      significantly greater weight loss at 12 months in intervention participants than
      in controls. The present study aimed to compare BeWEL intervention outcomes by
      participant deprivation status. METHODS: The intervention group of the BeWEL
      trial (n = 163) was classified by the Scottish Index of Multiple Deprivation
      (SIMD) quintiles into 'more deprived' (SIMD 1-2, n = 58) and 'less deprived'
      (SIMD 3-5, n = 105). Socio-economic and lifestyle variables were compared at
      baseline to identify potential challenges to intervention adherence in the more
      deprived. Between group differences at 12 months in primary outcome (change in
      body weight) and secondary outcomes (cardiovascular risk factors, diet, physical
      activity, knowledge of CRC risk and psychosocial variables) were assessed by
      deprivation status. RESULTS: At baseline, education (P = 0.001), income (P <
      0.001), spending on physical activity (P = 0.003) and success at previous weight
      loss attempts (P = 0.007) were significantly lower in the most deprived. At 12
      months, no between group differences by deprivation status were detected for
      changes in primary and main secondary outcomes. CONCLUSIONS: Despite potential
      barriers faced by the more deprived participants, primary and most secondary
      outcomes were comparable between groups, indicating that this intervention is
      unlikely to worsen health inequalities and is equally effective across socio
      economic groups.

PMID- 29171114
TI  - Prescription drug use in pregnancy and variations according to prior psychiatric
      history.
AB  - PURPOSE: Prescription drug use during pregnancy has increased during the past
      decades. However, little is known about prescription drug use for high-risk
      pregnancies. We aimed to estimate the prevalence of redeemed prescriptions in
      Danish pregnant women with and without previous psychiatric history. METHODS: A
      Danish population-based descriptive study of 981 392 pregnancies ending in live
      born singletons by 586 988 women aged 15 to 55 years between 1997 and 2012, of
      which 113 449 (11.6%) pregnancies were by women with a psychiatric history prior
      to the index pregnancy. All prescription drugs redeemed during pregnancy were
      identified, and dispensing patterns among the women were reported by therapeutic
      classes of drugs, calendar year of childbirth, and trimester. RESULTS: Overall,
      women with psychiatric history prior to pregnancy were more likely to fill a
      prescription (75.8%; 95% confidence interval [CI], 75.5-76.0%), compared with
      women with no psychiatric history (64.5%; 95% CI, 64.4-64.6%). The difference was
      observed even when psychotropic drug use was excluded and in all therapeutic
      classes except for antineoplastic and immunomodulating drugs. The most commonly
      prescribed drugs were anti-infectives. Approximately 44.7% (95% CI, 44.5-45.0%)
      of women with psychiatric history and 31.3% (95% CI, 31.2-31.4%) of women with no
      psychiatric history redeemed more than one therapeutic class of drugs.
      CONCLUSIONS: Women with a psychiatric history were more likely to redeem
      prescriptions during pregnancy across almost all drug classes, especially anti
      infectives. Two thirds of all women redeemed at least one prescription drug
      during pregnancy and one third more than one drug class. KEY POINTS We mapped
      prescription drug use of almost 600 000 women during almost one million
      pregnancies with focus on women with a history of psychiatric disorder before
      conception compared with women with no such history. Pregnant women with a
      previous psychiatric disorder were more likely to redeem prescription drugs
      compared with pregnant women without a previous psychiatric disorder. The
      observed overall difference was not due to obvious differences in psychotropic
      drug use. The difference was evident across calendar years, all trimesters, and
      almost all drug classes, but to a large extent in anti-infectives, among those
      mainly antibiotics. Two thirds of pregnant women redeemed prescription drugs
      during pregnancy, and one third redeemed more than one drug class. Health
      professionals should be aware of comorbid conditions requiring multiple drug use
      during pregnancy with the risk of unknown fetal effects.

PMID- 29171115
TI  - Carboplatin and programmed death-ligand 1 blockade synergistically produce a
      similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model.
AB  - AIM: In advanced, platinum resistant or refractory ovarian cancer (OC), the
      therapeutic efficacy of carboplatin is controversial. Although anti-programmed
      death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway blockages show great
      potential in cancer treatment, the antitumor effect of single anti-PD-L1 pathway
      monoclonal antibody (mAb) is not obvious in advanced or some poorly immunogenic
      tumors, including OC. We compared the effects of single or combined carboplatin
      and anti-PD-L1 mAb treatments and explored the possible antitumor mechanisms in a
      murine ID8 OC model. METHODS: C57BL/6 mice with established peritoneal ID8 OC
      were intraperitoneally injected with single or combined carboplatin and anti-PD
      L1 mAb. The formation time of ascites and their overall survival were recorded.
      The compositions of tumor-associated immune cells were analyzed by flow
      cytometry. RESULTS: A single treatment of carboplatin and combined carboplatin/PD
      L1 mAb induced a strong anti-ascites response. Mice treated with carboplatin
      presented the longest overall survival, followed by the combined remedy.
      Mechanistic investigation of the tumor microenvironment revealed that carboplatin
      and carboplatin/PD-L1 mAb increased antitumor effector CD4+ , CD8+ T cells and
      decreased immunosuppressive regulatory T and myeloid suppressor cells, giving
      rise to remarkably higher ratios of effector CD4+ , CD8+ T cells to regulatory T
      cells and myeloid suppressor cells in the peritoneal cavity. CONCLUSIONS: To our
      knowledge, this is the first report to compare the antitumor effect and potential
      mechanisms between carboplatin, PD-L1 mAb and their combination strategies in a
      murine ID8 OC model. The results of this study may deepen our understanding of OC
      and aid future preclinical experiments or clinical trials.

PMID- 29171116
TI  - Impact of weight loss on ablation outcome in obese patients with longstanding
      persistent atrial fibrillation.
AB  - AIMS: This study investigated the impact of weight loss in longstanding
      persistent (LSPAF) patients undergoing catheter ablation (CA). METHODS: Ninety
      consecutive obese LSPAF patients were approached; 58 volunteered to try weight
      loss interventions for up to 1 year (group 1), while 32 patients declined weight
      loss interventions and were included as a control (group 2). Both groups remained
      on antiarrhythmic drugs. If they continued to experience AF, CA was performed.
      Body weight was measured at 6-month intervals and arrhythmia status was assessed
      by event recorder, electrocardiogram (ECG), and Holter monitoring. Symptom
      severity and quality of life (QoL) were evaluated by AFSS and SF-36 survey,
      respectively. A scoring algorithm with two summary measures, physical component
      score (PCS) and mental component score (MCS), was prepared for QoL analysis.
      RESULTS: Significant reduction in body weight (median -24.9 (IQR -19.1 to -56.7)
      kg, P < 0.001) was observed in the group 1 patients, while no such change was
      seen in group 2. The PCS and MCS scores improved significantly in group 1 only,
      with a change from baseline of 8.4 +/- 3 (P = 0.013) and 12.8 +/- 8.2 (P < 0.02).
      However, AF symptom severity remained unchanged from baseline in both groups (P =
      0.84). All 90 patients eventually underwent CA and received PVAI+ posterior wall+
      non-PV triggers ablation. At 1-year follow-up after single procedure, 37 (63.8%)
      in group 1 and 19 (59.3%) patients in group 2 remained arrhythmia-free off AAD (P
      = 0.68). CONCLUSION: In this prospective analysis, in LSPAF patients weight loss
      improved QoL but had no impact on symptom severity and long-term ablation
      outcome.

PMID- 29171117
TI  - Predictive factors for emergent surgical intervention in patients with ovarian
      endometrioma hospitalized for pelvic inflammatory disease: A retrospective
      observational study.
AB  - AIM: The aim of this study was to identify predictive factors for emergent
      surgical interventions in patients with ovarian endometriomas hospitalized for
      pelvic inflammatory disease (PID). METHODS: We retrospectively identified 22
      patients with ovarian endometriomas who were hospitalized to manage PID. Patients
      were divided into two groups: those who required emergent surgery after failed
      antibiotic therapy (emergent surgery group, n = 6) and those who were discharged
      with successful antibiotic therapy (conservative group, n = 16). Logistic
      regression analysis was performed to analyze the factors associated with emergent
      surgery. RESULTS: Patients in the emergent surgery group were significantly more
      likely to have intrauterine or intrapelvic procedures before the onset of PID
      compared to those in the conservative group (83% vs 38%, odds ratio 8.33, 95%
      confidence interval 1.02-181.3; P = 0.048). The mean interval between the onset
      of PID symptoms and the commencement of parenteral antibiotic therapy was
      significantly longer in the emergent surgery compared to the conservative group
      (6.5 vs 1 day, odds ratio 1.28, 95% confidence interval 1.01-1.75; P = 0.041).
      CONCLUSION: A history of an intrauterine or intrapelvic procedure before the
      onset of PID was more likely to result in emergent surgery. A longer interval
      between the onset of PID symptoms and the commencement of parenteral antibiotics
      was also associated with emergent surgery. These findings could help to identify
      patients with ovarian endometriomas hospitalized with PID at higher risk of
      emergent surgical intervention.

PMID- 29171118
TI  - Translesional pressure gradient and leptomeningeal collateral status in
      symptomatic middle cerebral artery stenosis.
AB  - BACKGROUND AND PURPOSE: Leptomeningeal collateral (LMC) status governs the
      prognosis of large artery occlusive stroke, although factors determining LMC
      status are not fully elucidated. The aim was to investigate metrics affecting LMC
      status in such patients by using computational fluid dynamics (CFD) models based
      on computed tomography angiography (CTA). METHODS: In this cross-sectional study,
      patients with recent ischaemic stroke or transient ischaemic attack attributed to
      atherosclerotic M1 middle cerebral artery (MCA) stenosis (50%-99%) were
      recruited. Demographic, clinical and imaging data of these patients were
      collected. Ipsilesional LMC status was graded as good or poor by assessing the
      laterality of anterior and posterior cerebral arteries in CTA. A CFD model based
      on CTA was constructed to reflect focal hemodynamics in the distal internal
      carotid artery, M1 MCA and A1 anterior cerebral artery. Pressure gradients were
      calculated across culprit MCA stenotic lesions in CFD models. Predictors for good
      LMC status were sought in univariate and multivariate analyses. RESULTS: Amongst
      the 85 patients enrolled (mean age 61.5 +/- 10.9 years), 38 (44.7%) had good
      ipsilesional LMC status. The mean pressure gradient across MCA lesions was 14.8
      +/- 18.1 mmHg. Advanced age (P = 0.030) and a larger translesional pressure
      gradient (P = 0.029) independently predicted good LMCs. A lower fasting blood
      glucose level also showed a trend for good LMCs (P = 0.058). CONCLUSIONS: Our
      study suggested a correlation between translesional pressure gradient and
      maturation of LMCs in intracranial atherosclerotic disease. Further studies with
      more exquisite and dynamic monitoring of cerebral hemodynamics and LMC evolution
      are needed to verify the current findings.

PMID- 29171119
TI  - Abundant recent activity of retrovirus-like retrotransposons within and among
      flycatcher species implies a rich source of structural variation in songbird
      genomes.
AB  - Transposable elements (TEs) are genomic parasites capable of inserting virtually
      anywhere in the host genome, with manifold consequences for gene expression, DNA
      methylation and genomic stability. Notably, they can contribute to phenotypic
      variation and hence be associated with, for example, local adaptation and
      speciation. However, some organisms such as birds have been widely noted for the
      low densities of TEs in their genomes and this has been attributed to a potential
      dearth in transposition during their evolution. Here, we show that avian
      evolution witnessed diverse and abundant transposition on very recent timescales.
      First, we made an in-depth repeat annotation of the collared flycatcher genome,
      including identification of 23 new, retrovirus-like LTR retrotransposon families.
      Then, using whole-genome resequencing data from 200 Ficedula flycatchers, we
      detected 11,888 polymorphic TE insertions (TE presence/absence variations, TEVs)
      that segregated within and among species. The density of TEVs was one every 1.5
      2.5 Mb per individual, with heterozygosities of 0.12-0.16. The majority of TEVs
      belonged to some 10 different LTR families, most of which are specific to the
      flycatcher lineage. TEVs were validated by tracing the segregation of hundreds of
      TEVs across a three-generation pedigree of collared flycatchers and also by their
      utility as markers recapitulating the phylogenetic relationships among flycatcher
      species. Our results suggest frequent germline invasions of songbird genomes by
      novel retroviruses as a rich source of structural variation, which may have had
      underappreciated phenotypic consequences for the diversification of this species
      rich group of birds.

PMID- 29171120
TI  - Quality of development and reporting of dietetic intervention studies in primary
      care: a systematic review of randomised controlled trials.
AB  - BACKGROUND: High-quality research methodologies and clear reporting of studies
      are essential to facilitate confidence in research findings. The aim of the
      present study was to conduct an in-depth examination of the methodological
      quality and reporting of studies included in a recent systematic review of
      dietitians' effectiveness at providing individualised nutrition care to adult
      patients. METHODS: The methodological quality and reporting of 27 Randomised
      Controlled Trials (RCTs) were appraised using the UK Medical Research Council
      (MRC) Guidelines for complex interventions and the CONSORT checklist for
      reporting RCTs. A quality appraisal checklist was developed for each
      guideline/assessment tool aiming to evaluate the extent to which each study met
      the designated criteria. Excerpts from studies that best addressed criteria were
      collated to provide exemplary accounts of how criteria may be achieved in future
      studies. RESULTS: None of the reviewed studies met more than half of the MRC
      Guidance criteria, indicating that there is clear room for improvement in
      reporting the methodological underpinnings of these studies. Similarly, no
      studies met all criteria of the CONSORT checklist, suggesting that there is also
      room for improvement in the design and reporting of studies in this field.
      CONCLUSIONS: Dietitians, researchers and journal editors are encouraged to use
      the results and exemplary accounts from this review to identify key aspects of
      studies that could be improved in future research. Improving future research will
      enhance the quality of the evidence-base that investigates the outcomes of
      dietary interventions involving dietitians.

PMID- 29171121
TI  - Insular damage, new-onset atrial fibrillation and outcome after acute
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Cortical insular damage is associated with cardiac
      arrhythmias and an increased risk of death. We investigated the influence of
      insular damage on the outcome of patients with acute intracerebral hemorrhage as
      well as the frequency and predictors of new-onset atrial fibrillation (nAF).
      METHODS: We studied consecutive patients with intracerebral hemorrhage from 2013
      to 2016. We identified those patients who underwent continuous
      electrocardiographic monitoring (>=24 h), known atrial fibrillation and recent
      ischemic stroke. We prospectively collected demographic data, vascular risk
      factors, neurological severity, vital signs, radiological data, nAF and mortality
      at 3 months. Bivariate and multivariate regression analyses were performed.
      RESULTS: We evaluated 347 patients whose mean age was 73.5 +/- 14.0 years (50.7%
      of them were men). We selected 183 patients to study the frequency and risk
      factors of nAF (mean age, 69.1 +/- 14.7 years; 52.5% of them were men). We
      observed that 11/183 (6.0%) had nAF. Insular damage [odds ratio (OR), 7.6; 95%
      confidence interval (CI), 2.1-27.7] was associated with nAF. A total of 138/347
      patients died within the first 3 months and insular damage was detected in 99/347
      of them. Predictors of death were age (OR, 1.07; 95% CI, 1.04-1.10), blood
      glucose (OR, 1.00 per mg/dL;, 95% CI, 1.00-1.01), Glasgow Coma Scale score (OR,
      0.85; 95% CI, 0.77-0.92), hematoma volume (OR, 1.02 per mL; 95% CI, 1.01-1.04),
      intraventricular hemorrhage (OR, 1.93; 95% CI, 1.03-3.64) and insular damage (OR,
      3.98; 95% CI, 2.00-7.90). CONCLUSIONS: The frequency of nAF in our patients was
      6.0%. Insular damage was a risk factor for nAF and an independent predictor of
      death at 3 months.

PMID- 29171122
TI  - The Mutation in the Single-Crystal Structural Transformation Process, Induced by
      the Combined Stimuli of Temperature and Solvent.
AB  - A 2D coordination polymer containing a free ligand (Lf ), fixed by hydrogen
      bonds, transformed into a 3D metal-organic framework (MOF) in a single-crystal to
      single-crystal fashion. This transformation occurs through the combined stimuli
      of temperature and solvent. From 50 to 90  degrees C, a series of changes take
      place in a gradual form: the Lf is slowly moved to the cobalt center, which is
      accompanied by a contraction of unit cell and hydrogen bond. When the temperature
      rises to 95  degrees C, the hydrogen bond is destroyed, and Lf is suddenly
      combined with the cobalt ion to form an intricate 3D structure. This mutation
      process is irreversible and cannot occur just with the stimulus of either
      temperature or solvent. Notably, even under the combined stimuli, this mutation
      phenomena is difficult to reproduce when the solvent species and proportions
      change. DFT calculations were used to try to explain the nature of the
      phenomenon.

PMID- 29171123
TI  - Investigation of Known Genetic Mutations of Arabian Horses in Egyptian Arabian
      Foals with Juvenile Idiopathic Epilepsy.
AB  - BACKGROUND: The carrier status of lavender foal syndrome (LFS), cerebellar
      abiotrophy (CA), severe combined immunodeficiency (SCID), and
      occipitoatlantoaxial malformation (OAAM1) in foals with juvenile idiopathic
      epilepsy (JIE) is unknown. HYPOTHESIS/OBJECTIVES: To determine the carrier status
      of LFS, CA, SCID, and OAAM1 in foals with JIE. ANIMALS: Ten foals with JIE.
      MATERIALS AND METHODS: Archived DNA samples were tested for known genetic
      mutations causing LFS, CA, SCID, and OAAM1. The inclusion criteria consisted of
      having been diagnosed with JIE by ruling out other causes of seizures in foals
      and supported by electroencephalographic examination. RESULTS: Ten Egyptian
      Arabian horses (5 females and 5 males) were phenotyped as foals with JIE by
      electroencephalography (EEG). All foals were negative for the genetic mutations
      that cause LFS, CA, SCID, and OAAM1 except for 1 foal that was a carrier of CA.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Juvenile idiopathic epilepsy of Egyptian
      Arabian foals and LFS appear to be phenotypically and genetically distinct
      disorders. There was no apparent association between JIE and LFS, CA, SCID, and
      OAAM1.

PMID- 29171124
TI  - KDM6A promotes chondrogenic differentiation of periodontal ligament stem cells by
      demethylation of SOX9.
AB  - OBJECTIVES: KDM6A has been demonstrated critical in the regulation of cell fates.
      However, whether KDM6A is involved in cartilage formation remains unclear. In
      this study, we investigated the role of KDM6A in chondrogenic differentiation of
      PDLSCs, as well as the underlying epigenetic mechanisms. METHODS: KDM6A shRNA was
      transfected into PDLSCs by lentivirus. The chondrogenic differentiation potential
      of PDLSCs was assessed by Alcian blue staining. Immunofluorescence was performed
      to demonstrate H3K27me3 and H3K4me3 levels during chondrogenesis. SOX9, Col2a1,
      ACAN and miRNAs (miR-29a, miR-204, miR-211) were detected by real-time RT-PCR.
      Western blot was performed to evaluate SOX9, H3K27me3 and H3K4me3. RESULTS: The
      production of proteoglycans in PDLSCs was decreased after knockdown of KDM6A.
      Depletion of KDM6A inhibited the expression of SOX9, Col2a1, ACAN and resulted in
      increased H3K27me3 and decreased H3K4me3 levels. EZH2 inhibitor rescued the
      chondrogenic potential of PDLSCs after knockdown of KDM6A by regulating H3K27me3.
      Additionally, miR-29a, miR-204 and miR-211 were also involved in the process of
      PDLSCs chondrogenesis. CONCLUSIONS: KDM6A is required in chondrogenic
      differentiation of PDLSCs by demethylation of H3K27me3, and EZH2 inhibitor could
      rescue chondrogenesis of PDLSCs after knockdown of KDM6A. It could be inferred
      that upregulation of KDM6A or application of EZH2 inhibitor might improve
      mesenchymal stem cell mediated cartilage regeneration in inflammatory tissue
      destruction such as osteoarthritis.

PMID- 29171125
TI  - A Microsporidian Infection in Phoronids (Phylum Phoronida): Microsporidium
      phoronidi n. sp. from a Phoronis embryolabi.
AB  - Microsporidia-like spores (2.0-3.0 * 1.3-1.5 MUm) were discovered upon
      examination of histological sections taken from Phoronis embryolabi Temereva,
      Chichvarkhin 2017 found inhabiting burrows of shrimps Nihonotrypeae japonica
      (Decapoda, Callianassidae) from the Sea of Japan, Russia. Ultrastructural
      examination of spores revealed one nucleus and a uniform polar filament of 7-11
      coils. Representatives of the phylum Phoronida have never been recorded as hosts
      of microsporidia. Parasites developed in vasoperitoneal tissue and caused
      formation of multinucleate syncytia. Basing on unique host and fine morphology,
      we assign the novel finding to Microsporidium phoronidi n. sp. and place
      provisionally in the collective genus Microsporidium.

PMID- 29171126
TI  - Coincidence of pollen season with the first fetal trimester together with early
      pet exposure is associated with sensitization to cat and dog allergens in early
      childhood: A Finnish population-based study.
AB  - BACKGROUND: Children whose 11th fetal week falls in pollen season (spring)
      reportedly have an increased risk of sensitization to food allergens. No such
      finding has been reported for pet allergens. OBJECTIVE: The aim of the study was
      to (i) evaluate the incidence of pet (dog and cat) sensitization according to the
      season of the 11th fetal week and (ii) whether the association between pet
      exposure and respective sensitization is modified by the coincidence of the 11th
      fetal week with pollen season. METHODS: The study population comprised all
      children (born between 2001 and 2006) in the province of South Karelia, Finland
      (N = 5920). Their data of immunoglobulin E antibodies and skin prick tests to pet
      allergens (N = 538) were collected from patient records and linked with
      questionnaire data on pet exposure. RESULTS: The seasonal incidence peak of cat
      sensitization was observed in children whose 11th fetal week occurred in June
      (7.4%) and that of dog sensitization in April (3.8%) and June (4.7%). The
      relative rate (RR) for cat sensitization was 2.92 (95% CI 1.40-6.08) in children
      with cat exposure alone, 8.53 (4.07-17.86) in children with cat and fetal pollen
      exposures and 0.61 (0.20-1.83) in children exposed to pollen alone, compared with
      children without these exposures. The respective RRs for dog sensitization were
      2.17 (1.13-4.19), 4.40 (2.19-8.83) and 1.65 (0.77-3.53). CONCLUSIONS AND CLINICAL
      RELEVANCE: Coincidence of the first fetal trimester with pollen season
      strengthens the association between pet exposure and respective sensitization.
      Pollen exposure at early pregnancy may deviate immune system towards Th2-type
      reactivity promoting development of specific allergy in case allergen exposure
      occurred. Therefore, primary prevention of allergic diseases may need to begin
      during early pregnancy.

PMID- 29171127
TI  - How many geriatricians should, at minimum, be staffing health regions in
      Australia?
AB  - In any particular region, determining an adequate, quantifiable geriatrician full
      time equivalent required to run geriatric medicine services comprehensively -
      that is spanning both inpatient and outpatient settings - remains an imperfect
      science. Whilst workforce planning may be addressed through 'demand versus
      supply' simulations, 'specialist-to-patient ratios' (SPRs) may be a useful
      additional workforce metric. There has never been a yardstick SPR, which
      'defines' a satisfactory level of geriatrician manpower in any particular
      Australian hospital catchment. Here, a new methodology is proposed (tailored
      specifically to Australian geriatrics), illustrating how we may begin to
      transparently deduce such a national benchmark SPR. Allowing for some empiricism,
      the method presently favours an SPR approximating '0.4 full-time equivalent of
      geriatrician time per 10 000 head of population' in regions with 'average'
      population age distribution; this level of manpower may afford specialist
      assessment of targeted patients (widely capturing geriatric cases from acute to
      community settings). Further discussion on workforce planning methodologies is
      warranted.

PMID- 29171128
TI  - Soil pH as the chief modifier for regional nitrous oxide emissions: New evidence
      and implications for global estimates and mitigation.
AB  - Nitrous oxide (N2 O) is a greenhouse gas that also plays the primary role in
      stratospheric ozone depletion. The use of nitrogen fertilizers is known as the
      major reason for atmospheric N2 O increase. Empirical bottom-up models therefore
      estimate agricultural N2 O inventories using N loading as the sole predictor,
      disregarding the regional heterogeneities in soil inherent response to external N
      loading. Several environmental factors have been found to influence the response
      in soil N2 O emission to N fertilization, but their interdependence and relative
      importance have not been addressed properly. Here, we show that soil pH is the
      chief factor explaining regional disparities in N2 O emission, using a global
      meta-analysis of 1,104 field measurements. The emission factor (EF) of N2 O
      increases significantly (p < .001) with soil pH decrease. The default EF value of
      1.0%, according to IPCC (Intergovernmental Panel on Climate Change) for
      agricultural soils, occurs at soil pH 6.76. Moreover, changes in EF with N
      fertilization (i.e. DeltaEF) is also negatively correlated (p < .001) with soil
      pH. This indicates that N2 O emission in acidic soils is more sensitive to
      changing N fertilization than that in alkaline soils. Incorporating our findings
      into bottom-up models has significant consequences for regional and global N2 O
      emission inventories and reconciling them with those from top-down models.
      Moreover, our results allow region-specific development of tailor-made N2 O
      mitigation measures in agriculture.

PMID- 29171130
TI  - First experience in the UK of treating women with recurrent urinary tract
      infections with the bacterial vaccine Uromune(r).
AB  - OBJECTIVES: To determine the effectiveness of Uromune(r) in preventing recurrent
      urinary tract infections (UTIs) in women. PATIENTS AND METHODS: A total of 77
      women with microbiology-proven recurrent UTIs were given Uromune sublingual
      vaccine for a period of 3 months. Time to first UTI recurrence since treatment
      and adverse events were prospectively recorded in a follow-up period of up to 12
      months. RESULTS: Of the 77 women, 75 completed the treatment. Of the 75 women who
      completed treatment, 59 (78%) had no subsequent UTIs in the follow-up period.
      Prior to treatment, all women had experienced a minimum of three or more episodes
      of UTI during the preceding 12 months. Proportionally, the majority of
      recurrences occurred in postmenopausal women. One patient had to stop treatment
      because of an adverse event (rash over face and neck). CONCLUSION: This
      prospective study suggests that Uromune is safe and effective at preventing UTIs
      in women. Further research is required in larger groups of patients for longer
      treatment times. An international double-blind randomized control trial comparing
      Uromune with placebo is currently underway.

PMID- 29171129
TI  - The influence of body mass index and age on C-peptide at the diagnosis of type 1
      diabetes in children who participated in the diabetes prevention trial-type 1.
AB  - BACKGROUND/OBJECTIVE: The extent of influence of BMI and age on C-peptide at the
      diagnosis of type 1 diabetes (T1D) is unknown. We thus studied the impact of body
      mass index Z-scores (BMIZ) and age on C-peptide measures at and soon after the
      diagnosis of T1D. METHODS: Data from Diabetes Prevention Trial-Type 1 (DPT-1)
      participants <18.0 years at diagnosis was analyzed. Analyses examined
      associations of C-peptide measures with BMIZ and age in 2 cohorts: oral glucose
      tolerance tests (OGTTs) at diagnosis (n = 99) and mixed meal tolerance tests
      (MMTTs) <6 months after diagnosis (n = 80). Multivariable linear regression was
      utilized. RESULTS: Fasting and area under the curve (AUC) C-peptide from OGTTs (n
      = 99) at diagnosis and MMTTs (n = 80) after diagnosis were positively associated
      with BMIZ and age (P < .001 for all). Associations persisted when BMIZ and age
      were included as independent variables in regression models (P < .001 for all).
      BMIZ and age explained 31%-47% of the variance of C-peptide measures. In an
      example, 2 individuals with identical AUC C-peptide values had an approximate 5
      fold difference in values after adjustments for BMIZ and age. The association
      between fasting glucose and C-peptide decreased markedly when fasting C-peptide
      values were adjusted (r = 0.30, P < .01 to r = 0.07, n.s.). CONCLUSIONS: C
      peptide measures are strongly and independently related to BMIZ and age at and
      soon after the diagnosis of T1D. Adjustments for BMIZ and age cause substantial
      changes in C-peptide values, and impact the association between glycemia and C
      peptide. Such adjustments can improve assessments of beta-cell impairment at
      diagnosis.

PMID- 29171131
TI  - CPAP by helmet for treatment of acute respiratory failure after pediatric liver
      transplantation.
AB  - ARF after pediatric liver transplantation accounts for high rate of morbidity and
      mortality associated with this procedure. The role of CPAP in postoperative
      period is still unknown. The aim of the study was to describe current practice
      and risk factors associated with the application of helmet CPAP. In this
      retrospective observational cohort study, 119 recipients were divided into two
      groups based on indication to CPAP after extubation. Perioperative variables were
      studied, and determinants of CPAP application were analyzed in a multivariate
      logistic model. Sixty patients (60/114) developed ARF and were included in the
      CPAP group. No differences were found between the two groups for primary disease,
      graft type, and blood product transfused. At multivariate analysis, weight <11 kg
      (OR = 2.9; 95% CI = 1.1-7.3; P = .026), PaO2 /FiO2 <380 before extubation (OR =
      5.4; 95% CI = 2.1-13.6; P < .001), need of vasopressors (OR = 2.6; 95% CI = 1.1
      6.4; P = .038), and positive fluid balance >148 mL/kg (OR = 4.0; 95% CI = 1.6
      10.1; P = .004) were the main determinants of CPAP application. In the CPAP
      group, five patients (8.4%) needed reintubation. Pediatric liver recipients with
      lower weight, higher need of inotropes/vasopressors, higher positive fluid
      balance after surgery, and lower PaO2 /FiO2 before extubation were at higher odds
      of developing ARF needing CPAP application.

PMID- 29171132
TI  - Structured education to improve primary-care management of headache: how long do
      the benefits last? A follow-up observational study.
AB  - BACKGROUND AND PURPOSE: Our earlier study showed that structured education of
      general practitioners (GPs) improved their practice in headache management. Here
      the duration of this effect was assessed. METHODS: In a follow-up observational
      study in southern Estonia, subjects were the same six GPs as previously, managing
      patients presenting with headache as the main complaint. Data reflecting their
      practice were collected prospectively during a 1-year period commencing 2 years
      after the educational intervention. The primary outcome measure was referral rate
      (RR) to neurological services. Comparisons were made with baseline and post
      intervention data from the earlier study. RESULTS: In 366 patients consulting
      during the follow-up period, the RR was 19.9%, lower than at baseline (39.5%; P <
      0.0001) or post-intervention (34.7%; P < 0.0001). The RR was diagnosis-dependent:
      the biggest decline was for migraine. Use of headache diagnostic terms showed
      changes generally favouring specific terminology. In particular, the proportion
      of patients given migraine diagnoses greatly increased whilst use of the
      inappropriate M79.1 (Pericranial) myalgia almost disappeared. Requests for
      investigations, which had fallen from 26% (of patients seen) at baseline to 4%
      post-intervention, resurged to 23% (mostly laboratory investigations; requests
      for X-rays continued to dwindle). Initiation of treatment by the GPs remained at
      the post-intervention level of just over 80% (up from baseline 58%). CONCLUSIONS:
      Improvements in GPs' practice after a structured educational programme mostly
      last for >=3 years, some showing further betterment. A few measures suggest the
      beginnings of a decline towards baseline levels. This policy-informing evidence
      for continuing medical education indicates that the educational programme needs
      repeating every 2-3 years.

PMID- 29171133
TI  - Nurses' perceptions of preventing falls for patients with dementia in the acute
      hospital setting.
AB  - OBJECTIVES: Safe and high-quality care for patients with dementia is a key
      priority area of the Australian Commission on Safety and Quality in Health Care;
      however, caring for patients with dementia in the acute hospital setting is
      perceived as challenging. The aim of this analysis was to explore nurses'
      perspectives regarding fall prevention for patients with dementia in an acute
      care setting. METHODS: Secondary analysis of focus group data. Focus groups were
      conducted with nurses (n = 96) across six hospitals in New South Wales and
      Victoria. RESULTS: Nurses frequently reported issues relating to the physical
      environment of the acute care setting, competing priorities in a complex care
      setting and the need for one-on-one supervision for patients with dementia.
      CONCLUSION: Nurses report that one-on-one supervision is required to keep
      patients safe. Future research examining the acceptability and cost-effectiveness
      of volunteers providing this supervision is warranted in Australian hospitals.

PMID- 29171134
TI  - Cardiovascular autonomic dysfunction predicts increasing albumin excretion in
      type 1 diabetes.
AB  - OBJECTIVE: To determine the potential role of cardiovascular autonomic
      dysfunction in the development of renal complications in young people with type 1
      diabetes (T1D). METHODS: In this prospective study, 199 children and adolescents
      recruited to the Oxford Regional Prospective Study underwent assessment of
      autonomic function ~5 years after diagnosis, and were subsequently followed with
      longitudinal assessments of HbA1c and urine albumin-creatinine ratio (ACR) over
      8.6 +/- 3.4 years. Autonomic function was assessed with 4 standardized tests of
      cardiovascular reflexes: heart rate (HR) response to (1) Valsalva Maneuver, (2)
      deep breathing, (3) standing, and (4) blood pressure (BP) response to standing.
      Linear mixed models were used to assess the association between autonomic
      parameters and future changes in ACR. RESULTS: Independent of HbA1c , each SD
      increase in HR response to Valsalva Maneuver predicted an ACR increase of 2.16%
      [95% CI: 0.08; 4.28] per year (P = .04), while each SD increase in diastolic BP
      response to standing predicted an ACR increase of 2.55% [95% CI: 0.37; 4.77] per
      year (P = .02). The effect of HR response to standing on ACR reached borderline
      significance (-2.07% [95% CI: -4.11; 0.01] per year per SD increase, P = .051).
      CONCLUSIONS: In this cohort of young people with T1D, enhanced cardiovascular
      reflexes at baseline predicted future increases in ACR. These results support a
      potential role for autonomic dysfunction in the pathogenesis of diabetic
      nephropathy.

PMID- 29171135
TI  - Feasibility and pilot study of an intervention to support active lifestyles in
      youth with type 1 diabetes: The ActivPals study.
AB  - BACKGROUND: Evidence suggests youth with type 1 diabetes (T1D) have lower levels
      of physical activity (PA) than the general population. The ActivPals intervention
      aimed to support youth with T1D to lead an active lifestyle. METHODS: Twenty
      youth aged 7 to 16 years with T1D were recruited to a pilot randomized controlled
      trial. PA and quality of life (QoL) were measured using Actigraph GT3X+ monitor
      and Pediatric QoL scales at baseline and 1-month follow-up. A two-way, mixed
      ANOVA showed indicative effects of the intervention. Qualitative interviews were
      carried out with 16 participants to explore perceptions of the intervention.
      RESULTS: An increase in moderate to vigorous PA was reported in intervention and
      control groups from baseline to follow-up (F(1, 14) = 5.83; P = .03), with no
      significance between group differences. Participants in both groups reported
      significantly less overall diabetes "problems" (F(1, 16) = 7.93; P = .012) and
      significantly less lifestyle "problems" (F(1, 16) = 7.39; P = .015) at follow-up.
      However, both groups also reported significant increases in "problems" with the
      day-to-day diabetes routine (F(1,16) = 6.48; P = .022) at follow-up. Parents
      reported significant increased worry about their child's diabetes at follow-up,
      in both groups (F(1, 14) = 5.83; P = .046). There was no significant increase in
      reported hypoglycemic occurrences despite increased PA. The qualitative data
      highlight that goal setting, self-monitoring, and social support were effective
      motivators for increasing PA. CONCLUSIONS: A larger trial with longer follow-up
      should be conducted to explore the effect of the intervention on PA in youth with
      T1D.

PMID- 29171136
TI  - Prevalence and prognostic impact of electrocardiographic abnormalities in
      outpatients with extracardiac artery disease.
AB  - Identifying cardiac disease in patients with extracardiac artery disease (ECAD)
      is essential for clinical decision-making. Electrocardiography (ECG) is an easily
      accessible tool to unmask subclinical cardiac disease and to risk stratify
      patient with or without manifest cardiovascular disease (CV). We aimed to examine
      the prevalence and prognostic impact of ECG changes in outpatients with ECAD.
      Outpatients with carotid or lower extremity artery disease (n = 435) and
      community-based controls (n = 397) underwent resting ECG. The patients were
      followed during a median of 4.8 years for CV events (hospitalization or death
      caused by ischaemic heart disease, cardiac arrest, heart failure, or stroke). ECG
      abnormalities were classified according to the Minnesota Code. Major (33% versus
      15%, P<0.001) but not minor ECG abnormalities (23% versus 26%, P = 0.42) were
      significantly more common in patients versus controls. During the follow-up, 141
      patients experienced CV events. Both major ECG abnormalities [hazard ratio (HR)
      1.58, 95% confidence interval (CI) 1.11-2.25, P = 0.012] and any ECG
      abnormalities (HR 1.57, 95% CI 1.06-2.33, P = 0.024) were significantly
      associated with CV events after adjustment for potential risk factors. In
      conclusion, ECG abnormalities were common in these outpatients with ECAD. Major
      and any ECG abnormalities were independent predictors of CV events. Addition of
      easily accessible ECG information might be useful in risk stratification for such
      patients.

PMID- 29171137
TI  - Renewable Methane Generation from Carbon Dioxide and Sunlight.
AB  - The direct approach: Methane is a potential key player in the world's transition
      to a more sustainable energy future. The direct conversion of carbon dioxide into
      methane is highly desirable to lower the concentration of CO2 in the atmosphere
      and also to store renewable energy. This Highlight describes the first
      homogeneous system for the light-driven conversion of CO2 into CH4 .

PMID- 29171138
TI  - Enantioselective Synthesis of N,S-Acetals by an Oxidative Pummerer-Type
      Transformation using Phase-Transfer Catalysis.
AB  - Reported is the first enantioselective oxidative Pummerer-type transformation
      using phase-transfer catalysis to deliver enantioenriched sulfur-bearing
      heterocycles. This reaction includes the direct oxidation of sulfides to a
      thionium intermediate, followed by an asymmetric intramolecular nucleophilic
      addition to form chiral cyclic N,S-acetals with moderate to high
      enantioselectivites. Deuterium-labelling experiments were performed to identify
      the stereodiscrimination step of this process. Further analysis of the reaction
      transition states, by means of multidimensional correlations and DFT
      calculations, highlight the existence of a set of weak noncovalent interactions
      between the catalyst and substrate that govern the enantioselectivity of the
      reaction.

PMID- 29171139
TI  - Randomized, double-blind, placebo-controlled dose-finding study of the dipeptidyl
      peptidase-4 inhibitor linagliptin in pediatric patients with type 2 diabetes.
AB  - OBJECTIVE: To identify the dose of the dipeptidyl peptidase-4 (DPP-4) inhibitor
      linagliptin in pediatric patients with type 2 diabetes (T2D). METHODS: Double
      blind, randomized, controlled parallel group study comparing linagliptin 1 and 5
      mg once daily, with placebo in 39 patients with T2D aged 10 to below 18 years.
      The primary efficacy endpoint was the change from baseline in glycated hemoglobin
      (HbA1c) after 12 weeks of treatment. The key pharmacodynamic endpoint was DPP-4
      inhibition during steady-state. RESULTS: Compared to placebo, there was a dose
      dependent reduction in mean HbA1c of 0.48% and 0.63% with linagliptin 1 and 5 mg,
      respectively, associated with corresponding declines in mean fasting plasma
      glucose (FPG) of 5.6 and 34.2 mg/dL. Median DPP-4 inhibition was 38% with
      linagliptin 1 mg and 79% with linagliptin 5 mg. Geometric mean trough levels of
      linagliptin were 3.80 and 7.42 nmol/L in the 1 and 5 mg groups, respectively;
      levels that were slightly higher than in adult patients with T2D that were most
      likely caused by higher plasma DPP-4 concentrations in the study population.
      There were no drug-related adverse events during treatment with either dose of
      linagliptin. CONCLUSIONS: Linagliptin was well tolerated and induced dose
      dependent DPP-4 inhibition that was accompanied by corresponding reductions in
      HbA1c and FPG levels in young people with T2D. The results are consistent with
      the clinical efficacy and safety profile that have been reported for linagliptin
      in adult patients with T2D, favoring linagliptin 5 mg over 1 mg.

PMID- 29171140
TI  - Safety and efficacy of autoantigen-specific therapy with 2 doses of alum
      formulated glutamate decarboxylase in children with multiple islet autoantibodies
      and risk for type 1 diabetes: A randomized clinical trial.
AB  - OBJECTIVE: Treatments have failed to delay or stop the autoimmune process,
      preceding onset of type 1 diabetes. We investigated if autoantigen-specific
      treatment with alum-formulated glutamate decarboxylase (GAD-Alum) was safe and
      affected progression to type 1 diabetes in children with islet autoimmunity.
      METHODS: In an investigator-initiated, double-blind, placebo-controlled clinical
      trial, non-diabetic children aged 4 to 17.9 years with autoantibodies to
      glutamate decarboxylase (GADA) and at least one of insulinoma-associated protein
      2, insulin or zinc-transporter 8, were randomized, stratified by 2 or >=3 islet
      autoantibodies, to 2 injections of 20 MUg GAD-Alum or placebo, 30 days apart.
      Main outcome was safety, investigated by adverse events, hematology, chemistry,
      thyroid and celiac autoimmunity and titers of islet autoantibodies, and efficacy,
      investigated by cumulative incidence of diabetes onset over 5-year follow-up.
      Secondary variables: change in first-phase insulin release (FPIR) after
      intravenous glucose tolerance tests, fasting, 120 minutes and Area under the
      curve (AUC) C-peptide and p-glucose after oral glucose tolerance tests and HbA1c.
      RESULTS: Fifty children (median age: 5.2) were assigned 1:1 to GAD-Alum or
      placebo, all receiving full treatment and included in the analyses. GAD-Alum did
      not affect any safety parameter, while GADA titers increased (P = .001). Time to
      clinical diagnosis was not affected by treatment (hazard ratio, HR = 0.77, P =
      .574) in the full population or in the separate stratum groups. Treatment did not
      affect any of the secondary variables. CONCLUSIONS: GAD-Alum as a subcutaneous
      prime and boost injection was safe in prediabetic young children but did not
      affect progression to type 1 diabetes. The safety of GAD-Alum should prove useful
      in future prevention studies.

PMID- 29171141
TI  - The mental health of adolescents with and without mild/moderate intellectual
      disabilities in England: Secondary analysis of a longitudinal cohort study.
AB  - BACKGROUND: Children with mild/moderate intellectual disabilities are at greater
      risk for mental health problems, with socio-economic factors and adversity partly
      accounting for this. Fewer data are available for adolescents. METHODS: Secondary
      analysis was undertaken of the Next Steps annual panel study following a cohort
      through adolescence into adulthood containing self-report mental health data up
      to age 16/17. Participants with mild/moderate intellectual disabilities were
      identified through data linkage with educational records. RESULTS: Adolescents
      with mild/moderate intellectual disabilities were more likely than non-disabled
      peers to experience socio-economic disadvantage and bullying. Incidence rates of
      mental health problems were generally not significantly different between
      adolescents with and without intellectual disabilities. CONCLUSIONS: These
      findings are consistent with higher rates of persistent mental health problems
      beginning earlier among children with intellectual disabilities. Greater
      attention needs to be paid to the timecourse of mental health problems, and the
      impact of socio-economic factors, family and peers on mental health.

PMID- 29171143
TI  - Mechanical effects of negative pressure wound therapy on abdominal wounds -
      effects of different pressures and wound fillers.
AB  - The mechanical deformation of the wound edge resulting from negative pressure
      wound therapy (NPWT) at the standard setting of around -120 mmHg has positive
      effects in promoting wound healing. However, it may cause pain to the patient
      during treatment. It is therefore important to study the mechanical effects of
      the wound edges using lower pressure and different wound fillers. Abdominal
      wounds were created on eight pigs. The wounds were sealed for NPWT using foam or
      gauze. Negative pressures between -20 and -160 mmHg were applied, and the
      decrease in wound diameter and the force with which the edges of the wound were
      drawn together (wound edge force) were measured. Increasing levels of negative
      pressure resulted in a gradual decrease in wound diameter and increase in wound
      edge force and reached a maximum at -120 mmHg, which is the pressure commonly
      used in clinical practice. Both the decrease in wound diameter and the increase
      in wound edge force was greater with foam than with gauze. A pressure of -80 mmHg
      has only 15% less effect than -120 mmHg, while a lower pressure (-40 mmHg)
      diminished the effects on diameter and force markedly. The NPWT-induced decrease
      in wound diameter and increase in wound edge force are greater at higher levels
      of negative pressure and when using foam than when using gauze as a wound filler.
      It may be possible to tailor the type of wound filler and level of negative
      pressure to obtain the best balance between wound healing and patient comfort.

PMID- 29171142
TI  - Interleukin-6 regulates expression of Fos and Jun genes to affect the development
      of mouse preimplantation embryos.
AB  - AIM: We investigated whether recombinant mouse interleukin-6 (IL-6) affects the
      development of preimplantation embryos and induces the -signal transducers and
      activators of transcription (JAK-STAT) signaling pathway by binding IL-6 signal
      transducer (IL-6st) and regulating Fos and Jun gene expression, thereby
      accounting for the negative effect of superovulation on embryo development.
      METHODS: We compared rates of blastocyst formation from embryos cultured with
      different concentrations of IL-6 or/and anti-interleukin 6 receptor antibody
      (anti-IL-6RAb) in superovulated experimental and normal control groups. IL-6
      expression in preimplantation embryos was determined by immunofluorescence
      identification. Fos, Jun and IL-6st messenger RNA expression was detected by PCR
      and microarray experiments. RESULTS: Rates of blastocyst formation significantly
      decreased in superovulated embryos, whether or not they were incubated in 0.1, 1,
      25 or 50 pg/mL IL-6, (P < 0.01) compared to embryos from naturally ovulated
      controls, whereas incubation in 5 and 10 pg/mL IL-6 reversed the negative effects
      of superovulation. The addition of anti-IL-6RAb to naturally ovulated embryos
      reduced blastocyst rates to those of superovulated embryos. Gene chip analysis
      indicated that the JAK-STAT signaling pathway contained differentially expressed
      IL-6, IL-6st, Jun and Fos genes. Both anti-IL-6RAb or ovarian stimulation
      downregulated IL-6st, Jun, and Fos messenger RNA expression, but expression of
      the same three genes increased in 5 pg/mL IL-6. CONCLUSION: Ovarian stimulation
      negatively impacts the development of preimplantation embryos by reducing IL-6
      release. IL-6 affects the rate of development of zygotes to blastocyst by
      regulating IL-6st, Fos and Jun expression in the JAK-STAT signaling pathway.

PMID- 29171144
TI  - Altered fatty acid-binding protein 4 (FABP4) expression and function in human and
      animal models of hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the third leading cause of
      cancer-related mortality. Risk factors for developing HCC include viral
      hepatitis, alcohol and obesity. Fatty acid-binding proteins (FABPs) bind long
      chain free fatty acids (FFAs) and are expressed in a tissue-specific pattern;
      FABP1 being the predominant hepatic form, and FABP4 the predominant adipocyte
      form. The aims of this study were to investigate the expression and function of
      FABPs1-9 in human and animal models of obesity-related HCC. METHODS: FABP1-9
      expression was determined in a mouse model of obesity-promoted HCC. Based on
      these data, expression and function of FABP4 was determined in human HCC cells
      (HepG2 and HuH7) in vitro. Serum from patients with different underlying hepatic
      pathologies was analysed for circulating FABP4 levels. RESULTS: Livers from obese
      mice, independent of tumour status, exhibited increased FABP4 mRNA and protein
      expression concomitant with elevated serum FABP4. In vitro, FABP4 expression was
      induced in human HCC cells by FFA treatment, and led to FABP4 release into
      culture medium. Treatment of HCC cells with exogenous FABP4 significantly
      increased proliferation and migration of human HCC cells. Patient serum analysis
      demonstrated significantly increased FABP4 in those with underlying liver
      disease, particularly non-alcoholic fatty liver disease (NAFLD) and HCC.
      CONCLUSIONS: These data suggest FABP4, an FABP not normally expressed in the
      liver, can be synthesized and secreted by hepatocytes and HCC cells, and that
      FABP4 may play a role in regulating tumour progression in the underlying setting
      of obesity.

PMID- 29171145
TI  - Acute care nurses' views on family participation and collaboration in fundamental
      care.
AB  - AIMS AND OBJECTIVES: To understand the beliefs, attitudes and perceptions of
      nurses regarding family participation and collaboration in the care of their
      hospitalized adult relative. BACKGROUND: Family participation in care is known to
      enhance the quality of patient care. Nurses are uniquely placed to support such
      participation, including the delivery of fundamental care. However, nurses'
      attitudes and beliefs may help or hinder participation. DESIGN: A mixed methods
      approach with an exploratory sequential design was used. SETTING: A regional
      referral hospital in Australia. PARTICIPANTS: Nurses were eligible to participate
      in the study if they were permanent staff of the hospital, and who in their day
      to-day work had direct contact with adult patients and their families on acute
      care wards. METHODS: Observer-as-participant observation data and semi-structured
      interviews were undertaken. 30 hr of observational data were gathered, and 14
      nurses were interviewed. Data collection occurred between September and December
      2016. Following separate analysis, data were triangulated. RESULTS: Analysis
      uncovered two contrasting categories: (i) enacting family participation (four
      themes); and (ii) hindering family participation (five themes). CONCLUSION: The
      findings of our study demonstrated that the practices of nurses do not always
      align with healthcare policies, and strategies to support nurses to enact patient
      and family-centred practices are needed. RELEVANCE TO CLINICAL PRACTICE: Nurses
      can use these findings to make informed evidence-based changes to the way they
      practice and communicate with families to ensure fundamental care is delivered.

PMID- 29171146
TI  - OnabotulinumtoxinA in chronic migraine: predictors of response. A prospective
      multicentre descriptive study.
AB  - BACKGROUND AND PURPOSE: OnabotulinumtoxinA is a treatment specifically approved
      for the prophylaxis of chronic migraine in adults. The aim of this study was to
      assess the effectiveness of OnabotulinumtoxinA in chronic migraine after 1 year
      of treatment in a real-life setting and to identify clinical predictors of
      outcome. METHODS: We designed a prospective multicentre study performed in 13
      hospitals in Spain. Patients underwent a complete medical history and
      examination. They were treated with OnabotulinumtoxinA every 12 weeks for 1 year.
      Data about outcome, adverse events, abortive medication use, emergency room use
      and disability were collected at 3 and 12 months. RESULTS: A total of 725
      subjects completed the study. At 12 months, 79.3% showed >50% reduction in number
      of headaches per month and 94.9% reported no adverse events. Unilaterality of
      pain, fewer days of disability per month and milder headache at baseline were
      correlated with good outcome. Duration of disease <12 months increased the
      chances of response to treatment with OnabotulinumtoxinA (odds ratio, 1.470; 95%
      confidence interval, 1.123-2.174; P = 0.045). CONCLUSIONS: This study confirmed
      the effectiveness of treatment with OnabotulinumtoxinA after 1 year of treatment.
      The chances of a good outcome may be increased by starting treatment in the first
      12 months after chronic migraine diagnosis.

PMID- 29171147
TI  - Physical activity perceptions and behaviors among young adults with congenital
      heart disease: A mixed-methods study.
AB  - OBJECTIVE: A physically active lifestyle can help maintain positive physical and
      psychosocial health outcomes among adults with congenital heart disease (CHD).
      This study explored the physical activity perceptions and behaviors among young
      adults with CHD. DESIGN: This was a cross-sectional, mixed-methods study that
      included objectively measured physical activity assessment (accelerometer),
      individual semistructured interviews, and psychosocial questionnaires. RESULTS:
      Fifteen participants (67% male; 21 +/- 3 years old) with moderate (n = 10) or
      complex (n = 5) CHD were recruited from an outpatient adult CHD clinic.
      Participants accumulated 26 +/- 16 minutes of moderate-to-vigorous physical
      activity per day, and reported a high quality of life, moderate self-efficacy for
      exercise, and low cardiac-focused anxiety. Qualitative data indicated that
      participants reported more positive perceptions toward activity if their family
      members encouraged physical activity participation, including siblings that
      engaged in physical activity alongside participants. Participants described
      parents as supportive rather than overprotective. Activity precautions were
      perceived by participants as being instructions from cardiologists rather than
      restrictions by parents. Participants described some physical limitations
      compared to peers, but managed challenges by either working within their
      limitations or choosing activities that met their expectations and/or in which
      they could fully participate. Participants often described childhood physical
      activity in the context of school, physical education, and organized sports.
      Whereas physical activity in childhood was viewed as recreational, the cardiac
      health-promoting aspects became more prominent in adulthood. Activities performed
      during one's employment were considered sufficient to meet physical activity
      recommendation levels, and participants reported limited time and/or energy to
      participate in activity outside of work. CONCLUSIONS: The influence of family
      appeared to help participants adopt a positive perception toward activity
      participation in childhood that was carried forward to young adulthood. Future
      clinical work should target adolescents with CHD with less social supports and/or
      negative perceptions toward physical activity.

PMID- 29171148
TI  - Comorbidity and the increased mortality after hospitalization for stroke: a
      population-based cohort study.
AB  - : Essentials Comorbidity is prevalent in the stroke population and affects post
      stroke survival. A stroke patient cohort (n = 201 691) and a general population
      cohort were followed for survival. Cancer and advanced renal/liver disease
      substantially increased one-year stroke mortality. Tailoring stroke interventions
      according to comorbidity may reduce excess mortality. SUMMARY: Background
      Comorbidity is prevalent among stroke patients, affecting post-stroke survival.
      It remains unknown whether comorbidity impacts post-stroke mortality beyond the
      combined individual effects of stroke and comorbidity. Methods Using nationwide
      Danish databases, we performed a cohort study of 201 691 patients >= 18 years old
      with incident ischemic stroke, intracerebral or subarachnoid hemorrhage, or
      unspecified stroke during 1995-2012, and 992 942 adults from the general
      population, matched to stroke patients by birth year, sex and individual
      comorbidities in the Charlson Comorbidity Index. During up to 5 years of follow
      up, we computed standardized mortality rates (SMRs) to assess interaction
      contrasts as a measure of excess mortality not explained by the additive effects
      of stroke and comorbidity acting alone. Results Five-year post-stroke mortality
      was 48%, corresponding to an SMR of 187 deaths per 1000 person-years. During the
      30-day peak post-stroke mortality (SMR, 180 per 1000 person-months), interaction
      with comorbidity represented 23%, 34% and 51% of post-stroke mortality rates
      among patients with low (score = 1), moderate (score = 2-3) and high (score = 4+)
      comorbidity based on Charlson Comorbidity Index scores. The interaction accounted
      for 5% to 32% of subsequent 31-365-day post-stroke mortality rates, depending on
      comorbidity level. The interaction contrasts were most notable among comorbid
      patients with cancer, particularly with hematological or metastatic disease,
      followed by patients with moderate-to-severe liver or renal disease. Conclusion
      Comorbidity, notably cancer and advanced renal or liver disease, increased 1-year
      mortality after stroke beyond the combined effects expected from either disease
      acting alone.

PMID- 29171150
TI  - Maternal prepregnancy BMI or weight and offspring's blood pressure: Systematic
      review.
AB  - Emerging evidence suggests that maternal prepregnancy body mass index or weight
      (MPBW) may be associated with offspring's blood pressure (BP). Therefore, we
      conducted a systematic review-following the Preferred Reporting Items for
      Systematic Reviews and Meta-analyses statement-to assess and judge the evidence
      for an association between MPBW with offspring's later BP. Five data bases were
      searched without limits. Risk of bias was assessed using the "Tool to Assess Risk
      of Bias in Cohort Studies," and an evidence grade was allocated following the
      World Cancer Research Fund criteria. Of 2,011 publications retrieved, 16 studies
      (all cohort studies) were included in the systematic review; thereof, 5 studies
      (31%) were rated as good-quality studies. Overall, data from 63,959 participants
      were enclosed. Systolic BP was analysed in 15 (5 good quality), diastolic BP in
      12 (3 good quality), and mean arterial pressure in 3 (no good quality) studies.
      Five good-quality studies of MPBW with offspring's systolic BP as the outcome and
      1 good-quality study with offspring's diastolic BP as the outcome observed a
      significant association. However, after adding offspring's anthropometry
      variables to the statistical model, the effect attenuated in 4 studies with
      systolic BP to nonsignificance, the study with diastolic BP remained significant.
      No good-quality studies were found with respect to offspring's later mean
      arterial pressure. In conclusion, this systematic review found suggestive, but
      still limited, evidence for an association between MPBW with offspring's later
      BP. The available data suggest that the effect might be mainly mediated via
      offspring's anthropometry.

PMID- 29171151
TI  - Live-Cell MicroRNA Imaging through MnO2 Nanosheet-Mediated DD-A Hybridization
      Chain Reaction.
AB  - Innovative techniques to visualize native microRNAs (miRNAs) in live cells can
      dramatically impact current research on the roles of miRNA in biology and
      medicine. Here, we report a novel approach for live-cell miRNA imaging using a
      biodegradable MnO2 nanosheet-mediated DD-A FRET hybridization chain reaction
      (HCR). The MnO2 nanosheets can adsorb DNA hairpin probes and deliver them into
      live cells. After entering cells, the MnO2 nanosheets are degraded by cellular
      GSH. Then, the target miR-21 triggers cascaded assembly of the liberated hairpin
      probes into long dsDNA polymers, which brings each two FAMs (donor) and one TAMRA
      (acceptor) into close proximity to generate significantly enhanced DD-A FRET
      signals, which was discovered and proven by our previous report. We think the
      developed approach can serve as an excellent intracellular miRNAs detection tool,
      which promises the potential for biological and disease studies.

PMID- 29171153
TI  - Gene expression and delayed nephrogenesis in the growth-restricted rat foetus and
      neonate.

PMID- 29171152
TI  - Evaluation of three experimental in vitro models for the assessment of the
      mechanical cleansing efficacy of wound irrigation solutions.
AB  - The aim of this study was to compare different wound-rinsing solutions to
      determine differences in the efficiency and to evaluate three different in vitro
      models for wound cleansing. Different wound-rinsing solutions (physiological
      saline solution, ringer lactate solution for wound irrigation, water and a
      solution containing polihexanide and the surfactant undecylenamidopropyl-betain)
      were applied on standardised test models (one- and three-chamber model, flow-cell
      method and a biofilm model), each challenged with three different standardised
      wound test soils. In the one-chamber model saline showed a better effect on
      decontaminating proteins than the ringer lactate solution. In the flow-cell
      method, water performed better than physiological saline solution, whereas ringer
      lactate solution demonstrated the lowest cleansing effect. No obvious superiority
      between the two electrolyte-containing solutions was detectable in the biofilm
      model. Unfortunately, it was not possible to assess the protein decontamination
      qualities of the surfactant-containing solution because of the interference with
      the protein measurement. The flow-cell method was able to detect differences
      between different rinse solutions because it works at constant flow mechanics,
      imitating a wound-rinsing procedure. The three-chamber and the less-pronounced
      modified one-chamber method as well as the biofilm model had generated
      inhomogeneous results.

PMID- 29171154
TI  - Layperson's perception of axial midline angulation in asymmetric faces.
AB  - OBJECTIVE: Asymmetric facial features such as a deviated nose and chin are common
      and known to affect smile esthetics. When presented with these asymmetries, the
      clinician must consider the impact they will have on the smile design parameters
      especially the placement and angulation of the dental midline, which is a common
      starting point for a case involving smile design. The purpose of this article is
      to determine if the nose and chin deviations affect the perception of dental
      midline angulation. MATERIALS AND METHODS: An asymmetric facial model (AFM) was
      created from a digital symmetric facial model, used in a previous study by
      digitally deviating the nose and chin to the same side. Eight different pictures
      of this AFM were created, each with different degrees of maxillary midline
      angulation (both in and against the direction of the deviated nose and chin).
      Using a visual Likert scaled delivered via Websurvey in the private practice
      setting, one hundred and ninety-six randomly selected laypersons were asked to
      evaluate each image according to their own notions of beauty. RESULTS: A minor
      axial dental midline angulation of 3.5 degrees  can be perceived independently of
      the direction of the cant. All pictures where the midline was canted pointing in
      the opposite direction of nose and chin deviations presented lower rating mean
      values. CONCLUSIONS: Off-center noses and chins can influence the perceived
      attractiveness of a smile with a canted dental midline. The degree and direction
      of a canted midline can influence the harmony between the smile and overall face,
      with canting in the same direction of the asymmetric features being rated as more
      attractive. CLINICAL SIGNIFICANCE: The dental midline should be as vertically
      straight as possible. If a midline cant is present, however, it is more favorable
      to have a dental midline angulation which points in the same direction as nose
      and chin deviations, rather than in the opposite direction.

PMID- 29171155
TI  - Interactions of (2S,6S;2R,6R)-Hydroxynorketamine, a Secondary Metabolite of (R,S)
      Ketamine, with Morphine.
AB  - Ketamine and its primary metabolite norketamine attenuate morphine tolerance by
      antagonising N-methyl-d-aspartate (NMDA) receptors. Ketamine is extensively
      metabolized to several other metabolites. The major secondary metabolite
      (2S,6S;2R,6R)-hydroxynorketamine (6-hydroxynorketamine) is not an NMDA
      antagonist. However, it may modulate nociception through negative allosteric
      modulation of alpha7 nicotinic acetylcholine receptors. We studied whether 6
      hydroxynorketamine could affect nociception or the effects of morphine in acute
      or chronic administration settings. Male Sprague Dawley rats received
      subcutaneous 6-hydroxynorketamine or ketamine alone or in combination with
      morphine, as a cotreatment during induction of morphine tolerance, and after the
      development of tolerance induced by subcutaneous minipumps administering 9.6 mg
      morphine daily. Tail flick, hot plate, paw pressure and rotarod tests were used.
      Brain and serum drug concentrations were quantified with high-performance liquid
      chromatography-tandem mass spectrometry. Ketamine (10 mg/kg), but not 6
      hydroxynorketamine (10 and 30 mg/kg), enhanced antinociception and decreased
      rotarod performance following acute administration either alone or combined with
      morphine. Ketamine efficiently attenuated morphine tolerance. Acutely
      administered 6-hydroxynorketamine increased the brain concentration of morphine
      (by 60%), and brain and serum concentrations of 6-hydroxynorketamine were doubled
      by morphine pre-treatment. This pharmacokinetic interaction did not, however,
      lead to altered morphine tolerance. Co-administration of 6-hydroxynorketamine 20
      mg/kg twice daily did not influence development of morphine tolerance. Even
      though morphine and 6-hydroxynorketamine brain concentrations were increased
      after co-administration, the pharmacokinetic interaction had no effect on acute
      morphine nociception or tolerance. These results indicate that 6
      hydroxynorketamine does not have antinociceptive properties or attenuate opioid
      tolerance in a similar way as ketamine.

PMID- 29171156
TI  - The roles of CSFs on the functional polarization of tumor-associated macrophages.
AB  - Macrophages have a central role in numerous physiological processes, such as
      immune defense, maintenance of tissue homeostasis, wound healing, and
      inflammation. Moreover, in numerous severe disorders, such as cancer or chronic
      inflammation, their functions can be profoundly affected. Macrophages
      continuously sense their environment and adapt their phenotypes and functions to
      the local requirements; this process is called plasticity. In addition to stress
      signals, metabolites, and direct cell-contact interactions with surrounding
      cells, numerous cytokines play a central role in controlling macrophage
      polarization. In this review, we will focus on three human macrophage
      differentiation factors: macrophage colony-stimulating factor (M-CSF), IL-34, and
      granulocyte M-CSF. These CSFs allow human monocyte survival, promote their
      differentiation into macrophages, and control macrophage polarization as they
      give rise to cells with different phenotype and functions. Based on recent
      observations, the role of granulocyte CSF on macrophage polarization is also
      addressed. Finally, our current knowledge on the expression of these growth
      factors in tumor microenvironment and their impact on the generation and
      polarization of tumor-associated macrophages are summarized.

PMID- 29171157
TI  - Bioavailability of Terpenes and Postprandial Effect on Human Antioxidant
      Potential. An Open-Label Study in Healthy Subjects.
AB  - SCOPE: To assess bioavailability of terpenes in human plasma and their effect on
      oxidative stress biomarkers. METHODS AND RESULTS: In this open-label and single
      arm postprandial trial, seventeen healthy male volunteers (20-40 years old)
      follow a low-phytochemical diet for 5 days. Next, after overnight fasting,
      volunteers consume Mastiha powder (a natural resin rich in terpenes) dispersed in
      water. Blood samples are collected on time points 0 h (before ingestion) and 0.5,
      1, 2, 4, 6, and 24 h (post-ingestion). Ultra-high-pressure liquid chromatography
      high-resolution MS (UHPLC-HRMS/MS) is applied for high throughput analysis of
      plasma. Serum resistance to oxidation and oxidized LDL (oxLDL) levels are
      measured. UHPLC-HRMS/MS analysis shows that major terpenes are bioavailable since
      0.5 h after administration, reaching a peak between 2 h and 4 h. Serum resistance
      to oxidation, expressed as difference of tLAG (time point-0 h), starts to
      increase from 0.5 h. This increase reaches statistical significance at 4 h (402.3
      +/- 65.0 s), peaks at 6 h (524.6 +/- 62.9 s), and remains statistically
      significant until 24 h (424.2 +/- 48.0 s). oxLDL levels, expressed as %change
      from 0 h, are reduced significantly from time point-1 h until time point-6 h.
      CONCLUSION: Results demonstrate the terpene bioavailability pattern after oral
      administration of Mastiha. Terpenes are potential mediators of antioxidant
      defense in vivo.

PMID- 29171158
TI  - Genetic monitoring of open ocean biodiversity: An evaluation of DNA metabarcoding
      for processing continuous plankton recorder samples.
AB  - DNA metabarcoding is an efficient method for measuring biodiversity, but the
      process of initiating long-term DNA-based monitoring programmes, or integrating
      with conventional programs, is only starting. In marine ecosystems, plankton
      surveys using the continuous plankton recorder (CPR) have characterized
      biodiversity along transects covering millions of kilometres with time-series
      spanning decades. We investigated the potential for use of metabarcoding in CPR
      surveys. Samples (n = 53) were collected in two Southern Ocean transects and
      metazoans identified using standard microscopic methods and by high-throughput
      sequencing of a cytochrome c oxidase subunit I marker. DNA increased the number
      of metazoan species identified and provided high-resolution taxonomy of groups
      problematic in conventional surveys (e.g., larval echinoderms and hydrozoans).
      Metabarcoding also generally produced more detections than microscopy, but this
      sensitivity may make cross-contamination during sampling a problem. In some
      samples, the prevalence of DNA from large plankton such as krill masked the
      presence of smaller species. We investigated adding a fixed amount of exogenous
      DNA to samples as an internal control to allow determination of relative plankton
      biomass. Overall, the metabarcoding data represent a substantial shift in
      perspective, making direct integration into current long-term time-series
      challenging. We discuss a number of hurdles that exist for progressing DNA
      metabarcoding from the current snapshot studies to the requirements of a long
      term monitoring programme. Given the power and continually increasing efficiency
      of metabarcoding, it is almost certain this approach will play an important role
      in future plankton monitoring.

PMID- 29171159
TI  - Unilateral pectoralis major muscle flap for the treatment of sternal wounds due
      to Ludwig's angina.
AB  - Necrotising descending mediastinitis may rarely originate from Ludwig's angina,
      which is an infection of the submandibular space. The use of the bilateral
      pectoralis major muscle flap for the treatment of sternal wound dehiscence is
      common, but reports of the unilateral application of this flap are scarce. This
      study aims to report the use of the unilateral pectoralis major muscle flap for
      the treatment of sternotomy dehiscence in a patient with mediastinitis due to
      Ludwig's angina. A 21-year-old male patient underwent an exploratory cervicotomy
      and median sternotomy for drainage of a submandibular infection that extended to
      the anterior, retropharyngeal and mediastinal cervical spaces. The patient had
      dehiscence of the sternal wound, and the unilateral pectoralis major muscle flap
      was used for reconstruction of the defect. This flap was able to completely cover
      the area of dehiscence of the sternotomy, and the patient presented a good
      postoperative evolution, without complications. The reconstruction technique
      using the unilateral pectoralis major muscle flap was considered a good option
      for the treatment of sternotomy dehiscence. It is an adjuvant method in the
      treatment of infections such as mediastinitis and osteomyelitis of the sternum
      secondary to Ludwig's angina, allowing a stable coverage of the sternum.

PMID- 29171160
TI  - Joining the dots between omics and environmental management.
AB  - With the rapid advancement of DNA sequencing technologies and the substantial
      reduction of their running costs, environmental genomics and transcriptomics
      become more affordable and popular in environmental toxicology. In parallel,
      there are also speedy improvements of mass spectrometry and nuclear magnetic
      resonance spectrometry, enabling high-throughput analyses of proteins and
      metabolites in biological samples and promoting research studies in proteomics
      and metabolomics. By applying these high-throughput omics technologies,
      researchers can quickly generate an unprecedentedly vast amount of biological
      data that may be useful to environmental management. However, the current pace of
      applying omics information in environmental management is still very slow, and
      lags well behind the rapid development of omics-based research. This timely
      commentary, therefore, calls for joint efforts to increase this pace and join the
      dots between omics and environmental management, turning omics into practical
      tools. Herein, I explore how omics can contribute to risk assessment and
      management of chemicals, and recommend what we can do to facilitate and promote
      the use of omics information in environmental management. This article is
      especially dedicated to my role model, mentor, and friend, Peter M Chapman (1951
      2017), who sadly passed away on 26 September 2017. Integr Environ Assess Manag
      2018;14:169-173. (c) 2017 SETAC.

PMID- 29171161
TI  - Negative pressure wound therapy in complex cranio-maxillofacial and cervical
      wounds.
AB  - The care and the management of the healing of difficult wounds at the level of
      the skull-facial face many problems related to patient compliance and the need to
      perform multiple dressings, with long periods of healing and, occasionally, a
      very long hospitalisation period. The introduction and evolution of negative
      pressure wound therapy (NPWT) in the treatment of difficult wounds has resulted
      in better healing, with a drastic reduction in terms of time and biological costs
      to the patient and cost to the health care system. The main aim of this study is
      to describe and discuss, using out our experience, the usefulness of NPWT in the
      cranial-facial-cervical region. We studied 16 patients with complex wounds of the
      cranial-facial-cervical region treated with NPWT. We divided clinical cases in
      four groups: cervicofacial infectious disease, healing complications in
      oncological-reconstructive surgery, healing complications of injury with exposure
      of bone and/or internal fixations and healing complications in traumatic injury
      with loss of substance. We evaluated complete or incomplete wound healing;
      application time, related also to hospitalisation time; days of intensive care
      unit (ICU) stay; management of the upper airways; timing of medication renewal;
      and patient comfort and compliance (on a scale of 1-5). Depression values were
      always between -75 and -125 mmHg in a continuous aspiration pattern. For every
      patient, we used the ActiVAC Therapy Unit, derived from the vacuum-assisted
      closure system (Kinetic Concepts Inc., San Antonio, TX). Medication renewals were
      performed every 48-72 hours. The NPWT application time ranged from 4 to 22 days
      (mean of 11.57 day). Therapy was effective to gain a complete restitutio ad
      integrum in every patient included in the group of cervicofacial infectious
      disease. Therapy has, however, been well tolerated in our series; this is
      probably due to the decreased number of applications, the ease of use and the
      comfort of the system relative to traditional dressing. Results were satisfactory
      for most of cases treated; faster and more effective wound healing was achieved.
      The lower number of NPWT applications, relating to standard dressings, led to an
      increase in patient comfort and compliance and a decrease in the use of medical,
      and in some cases economic, resources according to international literature.

PMID- 29171162
TI  - New insights and advances in CHARGE syndrome: Diagnosis, etiologies, treatments,
      and research discoveries.
AB  - CHARGE syndrome is a multiple congenital anomaly condition caused, in a majority
      of individuals, by loss of function pathogenic variants in the gene CHD7. In this
      special issue of the American Journal of Medical Genetics part C, authors of
      eleven manuscripts describe specific organ system features of CHARGE syndrome,
      with a focus on recent developments in diagnosis, etiologies, and treatments.
      Since 2004, when CHD7 was identified as the major causative gene in CHARGE,
      several animal models (mice, zebrafish, flies, and frog) and cell-based systems
      have been developed to explore the underlying pathophysiology of this condition.
      In this article, we summarize those advances, highlight opportunities for new
      discoveries, and encourage readers to explore specific organ systems in more
      detail in each individual article. We hope the excitement around innovative
      research and development in CHARGE syndrome will encourage others to join this
      effort, and will stimulate other investigators and professionals to engage with
      individuals diagnosed as having CHARGE syndrome, their families, and their care
      providers.

PMID- 29171163
TI  - Surface changes of various bulk-fill resin-based composites after exposure to
      different food-simulating liquid and beverages.
AB  - OBJECTIVE: To evaluate surface roughness, hardness, and morphology changes of
      various bulk-fill resin composites eroded by different food-simulating liquids
      and beverages. MATERIALS AND METHODS: One hundred and thirteen specimens were
      fabricated in polytetrafluoroethylene cylindrical mold (10 mm in diameter and 4
      mm in thickness). Before immersion, baseline data of roughness, Vicker's
      microhardness were recorded and surface characteristics were examined using
      scanning electron microscopy (SEM). Each product of specimens (SDR, Dentsply;
      SonicFill, Kerr; Tetric N-Ceram Bulk Fill, Ivoclar Vivadent AG; and Filtek Bulk
      Fill, 3M ESPE) were divided into 5 groups for spicy and sour soup, spicy soup
      (Tom Yum), pineapple juice, passionfruit juice, and deionized water (served as a
      control). Specimens were then alternately immersed in storage agents for 5
      seconds and artificial saliva for 5 seconds over 10 cycles. Specimens were stored
      in artificial saliva for 22 hours. This process was repeated for 28 days. After
      immersion, surface hardness and roughness of specimens were evaluated at 7, 14,
      21, and 28 days and data were analyzed by two-way repeated ANOVA and Tukey's HSD
      (alpha = 0.05). Surface morphology of specimens was also examined on day 28.
      RESULTS: The SDR group had the most statistically significant decrement in
      hardness (25.65 +/- 1.74 kg/mm2 in mean difference) and increment in roughness
      (0.26 +/- 0.10 MUm in mean difference; P < .05). Passionfruit juice caused the
      most surface changes in bulk-fill resin composites. SEM photomicrographs showed
      surface changes of all resin composites in varying degrees. CONCLUSION: Acidic
      food-simulating liquids and beverages significantly increased the surface
      roughness and decreased surface microhardness of bulk-fill resin composites after
      evaluation at the end of the 28-day immersion period. CLINICAL SIGNIFICANCE: For
      restoration of the affected teeth in patients who consume acidic food and
      beverages, roughness and erosion of resin composites should be considered. All of
      bulk-fill resin-based composites except SDR may be suitable for restorations in
      these patients.

PMID- 29171165
TI  - ReadTools: A universal toolkit for handling sequence data from different
      sequencing platforms.
AB  - Sequencing whole genomes has become a standard research tool in many disciplines
      including Molecular Ecology, but the rapid technological advances in combination
      with several competing platforms have resulted in a confusing diversity of
      formats. This lack of standard formats causes several problems, such as
      undocumented preprocessing steps or the loss of information in downstream
      software tools, which do not account for the specifics of the different available
      formats. ReadTools is an open-source Java toolkit designed to standardize and
      preprocess read data from different platforms. It manages FASTQ- and SAM
      formatted inputs while dealing with platform-specific peculiarities and provides
      a standard SAM compliant output. The code and executable are available at
      https://github.com/magicDGS/ReadTools.

PMID- 29171164
TI  - Exercise performance, haemodynamics, and respiratory pattern do not identify
      heart failure patients who end exercise with dyspnoea from those with fatigue.
AB  - AIMS: The two main symptoms referred by chronic heart failure (HF) patients as
      the causes of exercise termination during maximal cardiopulmonary exercise
      testing (CPET) are muscular fatigue and dyspnoea. So far, a physiological
      explanation why some HF patients end exercise because of dyspnoea and others
      because of fatigue is not available. We assessed whether patients referring
      dyspnoea or muscular fatigue may be distinguished by different ventilator or
      haemodynamic behaviours during exercise. METHODS AND RESULTS: We analysed
      exercise data of 170 consecutive HF patients with reduced left ventricular
      ejection fraction in stable clinical condition. All patients underwent maximal
      CPET and a second maximal CPET with measurement of cardiac output by inert gas
      rebreathing at peak exercise. Thirty-eight (age 65.0 +/- 11.1 years) and 132
      (65.1 +/- 11.4 years) patients terminated CPET because of dyspnoea and fatigue,
      respectively. Haemodynamic and cardiorespiratory parameters were the same in
      fatigue and dyspnoea patients. VO2 was 10.4 +/- 3.2 and 10.5 +/- 3.3 mL/min/kg at
      the anaerobic threshold and 15.5 +/- 4.8 and 15.4 +/- 4.3 at peak, in fatigue and
      dyspnoea patients, respectively. In fatigue and dyspnoea patients, peak heart
      rate was 110 +/- 22 and 114 +/- 22 beats/min, and VE/VCO2 and VO2 /work
      relationship slopes were 31.2 +/- 6.8 and 30.6 +/- 8.2 and 10.6 +/- 4.2 and 11.4
      +/- 5.5 L/min/W, respectively. Peak cardiac output was 6.68 +/- 2.51 and 6.21 +/-
      2.55 L/min (P = NS for all). CONCLUSIONS: In chronic HF patients in stable
      clinical condition, fatigue and dyspnoea as reasons of exercise termination do
      not highlight different ventilatory or haemodynamic patterns during effort.

PMID- 29171166
TI  - Outcomes of Asian patients with localized prostate cancer treated with combined
      intensity modulated radiation therapy (IMRT) and high dose rate (HDR)
      brachytherapy: A single institution experience.
AB  - AIM: External beam radiotherapy (EBRT) followed by high dose rate (HDR)
      brachytherapy boost has demonstrated minimal toxicities and improved disease
      control rate compared with EBRT alone in observational and randomized studies
      with predominantly Caucasian patients. This study aims to report the outcomes of
      patients treated with this approach in our predominantly Asian population.
      METHODS: Medical records for patients with localized prostate cancer who received
      combined EBRT delivered via intensity modulated radiotherapy (IMRT) technique
      followed by HDR brachytherapy boost were retrospectively reviewed. Outcomes
      evaluated included 5-year biochemical recurrence-free survival (per Phoenix
      definition), overall survival and treatment toxicities. RESULTS: From June 2009
      to March 2015, 75 patients were treated with IMRT followed by HDR brachytherapy
      boost. Twenty patients (27%) had intermediate risk, 55 (74%) had high-risk
      disease. Median follow up was 64 months. All patients received IMRT to a median
      dose of 45 Gy to the pelvis followed by HDR brachytherapy boost. Sixty, 10 and 5
      patients received boost of 21 Gy in two fractions, 19 Gy in two fractions and 15
      Gy in a single fraction, respectively. All patients met the planning criteria
      adapted from RTOG 0815. The 5-year prostate-specific antigen (PSA) control was
      85.2% (80.3% and 100% for high-risk and intermediate-risk group, respectively).
      Cancer-specific survival and overall survival are 97.3% and 92.0%, respectively.
      Eleven (15%) patients developed biochemical failure, six of which had distant
      metastasis. Three (4%) developed grade 3 genitourinary toxicity (urethral
      stricture and/or cystitis) and none developed grade 3 radiation proctitis.
      CONCLUSION: Our outcomes are comparable to internationally published data and
      demonstrate reproducibility of this approach in our population.

PMID- 29171167
TI  - A clinical study comparing digital radiography and near-infrared
      transillumination in caries detection.
AB  - OBJECTIVE: The purpose of this study was to compare the effectiveness of
      detecting proximal carious lesions utilizing a new near-infrared
      transillumination (NIRTI) system (CariVu, Dexis) to traditional digital bitewing
      radiography (BWXR). MATERIALS AND METHODS: Thirty patients received four
      posterior BWXRs and all premolars and molars were individually imaged with the
      NIRTI device. Sixty-seven proximal carious lesions were classified based on their
      depth into enamel or dentin for both BWXR and NIRTI images. RESULTS: The caries
      depth classification between the two systems were strongly correlated (rs  =
      0.66; Spearman range: 0.60-0.79 = strong) and significant (P < .001) with a
      median score of 3 for NIRTI and 2 for BWXR. CONCLUSIONS: The new NIRTI system
      (CariVu) may serve as an adjunct to BWXR in the diagnosis of proximal caries.
      CLINICAL SIGNIFICANCE: The NIRTI system could serve as an adjunct diagnostic
      system that could be used in high-caries risk programs where patients are closely
      monitored with regimented follow-up appointments. NIRTI could also be beneficial
      with pregnant or pediatric patients, and in situations where radiography may not
      be available such as remote humanitarian missions.

PMID- 29171168
TI  - Pilocytic astrocytoma with leptomeningeal spread in a patient with incontinentia
      pigmenti presenting with unilateral nystagmus.
AB  - Incontinentia pigmenti (IP) is a genetic disorder caused by mutations in IKBKG,
      leading to functional loss of nuclear factor kappa B (NF-KB). We report the case
      of a 6-month-old female child with IP who presented with unilateral nystagmus and
      was found to have a pilocytic astrocytoma with leptomeningeal spread. Enhanced
      understanding of the relationship between NF-KB, along with its upstream
      regulators, and tumorigenesis may shed light on whether a subset of patients with
      IP may be at increased risk for neoplasia.

PMID- 29171169
TI  - No effect of transcranial direct current stimulation of the dorsolateral
      prefrontal cortex on short-term memory.
AB  - INTRODUCTION: Short-term memory refers to the capacity for holding information in
      mind for a short period of time with conscious memorization. It is an important
      ability for daily life and is impaired in several neurological and psychiatric
      disorders. Anodal transcranial direct current stimulation (tDCS) applied to the
      dorsolateral prefrontal cortex (DLPFC) was reported to enhance the capability of
      short-term memory in healthy subjects. However, results were not consistent and
      what is the possible impact factor is not known. One important factor that may
      significantly influence the effect of tDCS is the timing of tDCS administration.
      AIMS: In order to explore whether tDCS impact short-term memory and the optimal
      timing of tDCS administration, we applied anodal tDCS to the left DLPFC to
      explore the modulatory effect of online and off-line tDCS on digit span as well
      as visual short-term memory performance in healthy subjects. RESULTS: Results
      showed tDCS of the left DLPFC did not influence intentional digit span memory
      performance, whether before the task or during the task. In addition, tDCS of the
      DLPFC administered before the task showed no effect on visual short-term memory,
      while there was a trend of increase in false alarm when tDCS of the DLPFC
      administered during the task. CONCLUSIONS: These results did not provide evidence
      for the enhancement of short-term memory by tDCS of the left DLPFC in healthy
      subjects, but it suggested an importance of administration time for visual short
      term memory. Further studies are required to taking into account the baseline
      performance of subjects and time-dependence feature of tDCS.

PMID- 29171170
TI  - Reestablishment of individual sleep structure during a single 14-h recovery sleep
      episode after 58 h of wakefulness.
AB  - Sleep structure is highly stable within individuals but different between
      individuals. The present study investigated robustness of the individual sleep
      structure to extended total sleep deprivation. Seventeen healthy men spent a
      baseline night (23:00-07:00 hours), 58 h of sleep deprivation and a 14-h recovery
      night (17:00-07:00 hours) in the laboratory. Intraclass correlation coefficients
      showed that the agreement between baseline and recovery with respect to the
      proportion of the different sleep stages increased as a function of recovery
      sleep duration. High values were reached for most of the sleep stages at the end
      of 14 h of recovery sleep (intraclass correlation coefficients between 0.38 and
      0.76). If sleep duration of the recovery night is extended to 14 h, sleep stage
      distribution resembles that of a baseline night underlining the robustness of the
      individual sleep structure.

PMID- 29171171
TI  - Sleep restriction and cognitive load affect performance on a simulated
      marksmanship task.
AB  - Sleep restriction degrades cognitive and motor performance, which can adversely
      impact job performance and increase the risk of accidents. Military personnel are
      prone to operating under sleep restriction, and previous work suggests that
      military marksmanship may be negatively affected under such conditions. Results
      of these studies, however, are mixed and have often incorporated additional
      stressors (e.g. energy restriction) beyond sleep restriction. Moreover, few
      studies have investigated how the degree of difficulty of a marksmanship task
      impacts performance following sleep restriction. The purpose of the current
      experiment was to study the effects of sleep restriction on marksmanship while
      minimizing the potential influence of other forms of stress. A friend-foe
      discrimination challenge with greater or lesser degrees of complexity (high
      versus low load) was used as the primary marksmanship task. Active duty Soldiers
      were recruited, and allowed 2 h of sleep every 24 h over a 72-h testing period.
      Marksmanship tasks, cognitive assessment metrics and the NASA-Task Load Index
      were administered daily. Results indicated that reaction times to shoot foe
      targets and signal friendly targets slowed over time. In addition, the ability to
      correctly discriminate between friend and foe targets significantly decreased in
      the high-cognitive-load condition over time despite shot accuracy remaining
      stable. The NASA-Task Load Index revealed that, although marksmanship performance
      degraded, participants believed their performance did not change over time. These
      results further characterize the consequences of sleep restriction on
      marksmanship performance and the perception of performance, and reinforce the
      importance of adequate sleep among service members when feasible.

PMID- 29171172
TI  - Cost-effectiveness of routine viral load monitoring in low- and middle-income
      countries: a systematic review.
AB  - INTRODUCTION: Routine viral load monitoring for HIV-1 management of persons on
      antiretroviral therapy (ART) has been recommended by the World Health
      Organization (WHO) to identify treatment failure. However, viral load testing
      represents a substantial cost in resource constrained health care systems. The
      central challenge is whether and how viral load monitoring may be delivered such
      that it maximizes health gains across the population for the costs incurred. We
      hypothesized that key features of program design and delivery costs drive the
      cost-effectiveness of viral load monitoring within programs. METHODS: We
      conducted a systematic review of studies on the cost-effectiveness of viral load
      monitoring in low- and middle-income countries (LMICs). We followed the Cochrane
      Collaboration guidelines and the PRISMA reporting guidelines. RESULTS AND
      DISCUSSION: We identified 18 studies that evaluated the cost-effectiveness of
      viral load monitoring in HIV treatment programs. Overall, we identified three key
      factors that make it more likely for viral load monitoring to be cost-effective:
      1) Use of effective, lower cost approaches to viral load monitoring (e.g. use of
      dried blood spots); 2) Ensuring the pathway to health improvement is established
      and that viral load results are acted upon; and 3) Viral load results are used to
      simplify HIV care in patients with viral suppression (i.e. differentiated care,
      with fewer clinic visits and longer prescriptions). Within the context of
      differentiated care, viral load monitoring has the potential to double the health
      gains and be cost saving compared to the current standard (CD4 monitoring).
      CONCLUSIONS: The cost-effectiveness of viral load monitoring critically depends
      on how it is delivered and the program context. Viral load monitoring as part of
      differentiated HIV care is likely to be cost-effective. Viral load monitoring in
      differentiated care programs provides evidence that reduced clinical engagement,
      where appropriate, is not impacting health outcomes. Introducing viral load
      monitoring without differentiated care is unlikely to be cost-effective in most
      settings and results in lost opportunity for health gains through alternative
      uses of limited resources. As countries scale up differentiated care programs,
      data on viral suppression outcomes and costs should be collected to evaluate the
      on-going cost-effectiveness of viral load monitoring as utilized in practice.

PMID- 29171173
TI  - Recent progress on fabrication and drug delivery applications of nanostructured
      hydroxyapatite.
AB  - Through this brief review, we provide a comprehensive historical background of
      the development of nanostructured hydroxyapatite (nHAp), and its application
      potentials for controlled drug delivery, drug conjugation, and other biomedical
      treatments. Aspects associated with efficient utilization of hydroxyapatite (HAp)
      nanostructures such as their synthesis, interaction with drug molecules, and
      other concerns, which need to be resolved before they could be used as a
      potential drug carrier in body system, are discussed. This review focuses on the
      evolution of perceptions, practices, and accomplishments in providing improved
      delivery systems for drugs until date. The pioneering developments that have
      presaged today's fascinating state of the art drug delivery systems based on HAp
      and HAp-based composite nanostructures are also discussed. Special emphasis has
      been given to describe the application and effectiveness of modified HAp as drug
      carrier agent for different diseases such as bone-related disorders, carriers for
      antibiotics, anti-inflammatory, carcinogenic drugs, medical imaging, and protein
      delivery agents. As only a very few published works made comprehensive evaluation
      of HAp nanostructures for drug delivery applications, we try to cover the three
      major areas: concepts, practices and achievements, and applications, which have
      been consolidated and patented for their practical usage. The review covers a
      broad spectrum of nHAp and HAp modified inorganic drug carriers, emphasizing some
      of their specific aspects those needed to be considered for future drug delivery
      applications. This article is categorized under: Implantable Materials and
      Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and
      Drug Discovery > Nanomedicine for Respiratory Disease Nanotechnology Approaches
      to Biology > Cells at the Nanoscale.

PMID- 29171174
TI  - The Influence of Self-Efficacy, Fear-Avoidance Belief, and Coping Styles on
      Quality of Life for Chinese Patients with Chronic Nonspecific Low Back Pain: A
      Multisite Cross-Sectional Study.
AB  - BACKGROUND: As a bio-psycho-social issue, chronic low back pain (CLBP) has been a
      significant topic in health management, and patients' quality of life (QOL) is
      gaining extensive attention. Self-efficacy, pain fear-avoidance belief (FAB), and
      coping styles play important roles in the QOL of CLBP patients. However, it
      remains unclear how self-efficacy and FAB influence QOL through specific coping
      styles. This study aimed to explore the influencing paths of self-efficacy, FAB,
      and coping styles on the QOL of patients with CLBP. METHODS: This study relies on
      a multisite, cross-sectional design involving 221 CLBP patients. Stepwise
      multiple regression and structural equation modeling were employed. RESULTS: CLBP
      patients lived with a poor global QOL. Self-efficacy played a direct, positive
      role in predicting QOL for patients with CLBP (beta = 0.35), and it also played
      an indirect, positive role in predicting QOL (beta = 0.19) through active coping
      styles (beta = 0.31). FAB played a direct, negative role in predicting QOL (beta
      = -0.33), and it also played an indirect, negative role in predicting QOL (beta =
      -0.32) through passive coping styles (beta = 0.32). CONCLUSIONS: Self-efficacy
      and FAB are both directly and indirectly related to global QOL, and coping styles
      are important mediating variables. Self-efficacy and active coping are protective
      factors for the QOL of CLBP patients, while FAB and passive coping are risk
      factors. Health education strategies are recommended by medical personnel to
      enhance CLBP patients' pain self-efficacy, decrease pain FAB, and modify pain
      coping styles, so that their global QOL can be improved.

PMID- 29171175
TI  - Computational predictions of damage propagation preceding dissection of ascending
      thoracic aortic aneurysms.
AB  - Dissections of ascending thoracic aortic aneurysms (ATAAs) cause significant
      morbidity and mortality worldwide. They occur when a tear in the intima-media of
      the aorta permits the penetration of the blood and the subsequent delamination
      and separation of the wall in 2 layers, forming a false channel. To predict
      computationally the risk of tear formation, stress analyses should be performed
      layer-specifically and they should consider internal or residual stresses that
      exist in the tissue. In the present paper, we propose a novel layer-specific
      damage model based on the constrained mixture theory, which intrinsically takes
      into account these internal stresses and can predict appropriately the tear
      formation. The model is implemented in finite-element commercial software Abaqus
      coupled with user material subroutine. Its capability is tested by applying it to
      the simulation of different exemplary situations, going from in vitro bulge
      inflation experiments on aortic samples to in vivo overpressurizing of patient
      specific ATAAs. The simulations reveal that damage correctly starts from the
      intimal layer (luminal side) and propagates across the media as a tear but never
      hits the adventitia. This scenario is typically the first stage of development of
      an acute dissection, which is predicted for pressures of about 2.5 times the
      diastolic pressure by the model after calibrating the parameters against
      experimental data performed on collected ATAA samples. Further validations on a
      larger cohort of patients should hopefully confirm the potential of the model in
      predicting patient-specific damage evolution and possible risk of dissection
      during aneurysm growth for clinical applications.

PMID- 29171176
TI  - Metastasis-specific patterns of response and progression with anti-PD-1 treatment
      in metastatic melanoma.
AB  - This study evaluated patterns of response as discerned by comprehensive
      metastasis-specific analysis in metastatic melanoma patients receiving anti-PD-1
      antibodies. Bi-dimensional measurements of every metastasis in patients enrolled
      in the KEYNOTE-001 trial at a single institution were obtained at baseline and
      throughout treatment. Twenty-seven evaluable patients had 399 baseline metastases
      measurable on CT imaging. Complete response (CR) which occurred in 52.6% of
      metastases was smaller (mean 223 mm2 versus 760 mm2 , p < .01) and occurred more
      frequently in the lungs (65% versus 39.4%, p < .01). Response was heterogenous
      (new/progressing metastases alongside CR metastases) at first assessment in 4/14
      patients with objective response (OR) as opposed to 7/13 patients with non-OR. CR
      of individual metastases is common and influenced by site and size. Most patients
      with OR demonstrate homogenous regression in all metastases at the first
      assessment. In contrast, patients with early heterogeneity had a poor outcome.

PMID- 29171177
TI  - Extracellular matrix remodeling in 3D: implications in tissue homeostasis and
      disease progression.
AB  - The extracellular matrix (ECM) plays a critical role in regulating cell behavior
      during tissue homeostasis and in disease progression. Through a combination of
      adhesion, contraction, alignment of ECM proteins and subsequent degradation,
      cells change the chemical, mechanical, and physical properties of their
      surrounding matrix. Other contributing factors to matrix remodeling are the de
      novo synthesis of ECM proteins, post-translational modifications and receptor
      mediated internalization. In this review, we highlight how each of these
      processes contributes to the maintenance of homeostasis and in disease conditions
      such as cancer and liver fibrosis. This article is categorized under: Implantable
      Materials and Surgical Technologies > Nanotechnology in Tissue Repair and
      Replacement.

PMID- 29171178
TI  - HIV viral load monitoring among key populations in low- and middle-income
      countries: challenges and opportunities.
AB  - INTRODUCTION: Key populations bear a disproportionate HIV burden and have
      substantial unmet treatment needs. Routine viral load monitoring represents the
      gold standard for assessing treatment response at the individual and programme
      levels; at the population-level, community viral load is a metric of HIV
      programme effectiveness and can identify "hotspots" of HIV transmission.
      Nevertheless, there are specific implementation and ethical challenges to
      effectively operationalize and meaningfully interpret viral load data at the
      community level among these often marginalized populations. DISCUSSION: Viral
      load monitoring enhances HIV treatment, and programme evaluation, and offers a
      better understanding of HIV surveillance and epidemic trends. Programmatically,
      viral load monitoring can provide data related to HIV service delivery coverage
      and quality, as well as inequities in treatment access and uptake. From a
      population perspective, community viral load data provides information on HIV
      transmission risk. Furthermore, viral load data can be used as an advocacy tool
      to demonstrate differences in service delivery and to promote allocation of
      resources to disproportionately affected key populations and communities with
      suboptimal health outcomes. However, in order to perform viral load monitoring
      for individual and programme benefit, health surveillance and advocacy purposes,
      careful consideration must be given to how such key population programmes are
      designed and implemented. For example, HIV risk factors, such as particular sex
      practices, sex work and drug use, are stigmatized or even criminalized in many
      contexts. Consequently, efforts must be taken so that routine viral load
      monitoring among marginalized populations does not cause inadvertent harm.
      Furthermore, given the challenges of reaching representative samples of key
      populations, significant attention to meaningful recruitment, decentralization of
      care and interpretation of results is needed. Finally, improving the
      interoperability of health systems through judicious use of biometrics or
      identifiers when confidentiality can be maintained is important to generate more
      valuable data to inform monitoring programmes. CONCLUSIONS: Opportunities for
      expanded viral load monitoring could and should benefit all those affected by
      HIV, including key populations. The promise of the increasing routinization of
      viral load monitoring as a tool to advance HIV treatment equity is great and
      should be prioritized and appropriately implemented within key population
      programmatic and research agendas.

PMID- 29171179
TI  - Optimal timing of viral load monitoring during pregnancy to predict viraemia at
      delivery in HIV-infected women initiating ART in South Africa: a simulation
      study.
AB  - INTRODUCTION: HIV viral load (VL) monitoring is a central tool to evaluate ART
      effectiveness and transmission risk. There is a global movement to expand VL
      monitoring following recent recommendations from the World Health Organization
      (WHO), but there has been little research into VL monitoring in pregnant women.
      We investigated one important question in this area: when and how frequently VL
      should be monitored in women initiating ART during pregnancy to predict VL at the
      time of delivery in a simulated South African population. METHODS: We developed a
      mathematical model simulating VL from conception through delivery using VL data
      from the Maternal and Child Health - Antiretroviral Therapy (MCH-ART) cohort. VL
      was modelled based on three major compartments: pre-ART VL, viral decay
      immediately after ART initiation and viral maintenance (including viral
      suppression and viraemic episodes). Using this simulation, we examined the
      performance of various VL monitoring schema in predicting elevated VL at
      delivery. RESULTS AND DISCUSSION: If WHO guidelines for non-pregnant adults were
      used, the majority of HIV-infected pregnant women (69%) would not receive a VL
      test during pregnancy. Most models that based VL monitoring in pregnancy on the
      time elapsed since ART initiation (regardless of gestation) performed poorly
      (sensitivity <50%); models that based VL measures in pregnancy on the woman's
      gestation (regardless of time on ART) appeared to perform better overall
      (sensitivity >60%). Across all permutations, inclusion of pre-ART VL values had a
      negligible impact on predictive performance (improving test sensitivity and
      specificity <6%). Performance of VL monitoring in predicting VL at delivery
      generally improved at later gestations, with the best performing option a single
      VL measure at 36 weeks' gestation. CONCLUSIONS: Development and evaluation of a
      novel simulation model suggests that strategies to measure VL relative to
      gestational age may be more useful than strategies relative to duration on ART,
      in women initiating ART during pregnancy, supporting better integration of
      maternal and HIV health services. Testing turnaround times require careful
      consideration, and point-of-care VL testing may be the best approach for
      measuring VL at delivery. Broadening the scope of this simulation model in the
      light of current scale up of VL monitoring in high burden countries is important.

PMID- 29171181
TI  - Regulation of cell proliferation in the retinal pigment epithelium: Differential
      regulation of the death-associated protein like-1 DAPL1 by alternative MITF
      splice forms.
AB  - Vertebrate eye development and homoeostasis critically depend on the regulation
      of proliferation of cells forming the retinal pigment epithelium (RPE). Previous
      results indicated that the death-associated protein like-1 DAPL1 cell
      autonomously suppresses RPE proliferation in vivo and in vitro. Here, we show in
      human RPE cell lines that the pigment cell transcription factor MITF regulates
      RPE cell proliferation by upregulating DAPL1 expression. DAPL1 regulation by MITF
      is, however, mediated predominantly by (-) MITF, one of two alternative splice
      isoforms of MITF that lacks six residues located upstream of the DNA-binding
      basic domain. Furthermore, we find that the regulation of DAPL1 by MITF is
      indirect in that (-) MITF stimulates the transcription of Musashi homolog-2
      (MSI2), which negatively regulates the processing of the anti-DAPL1 microRNA miR
      7. Our results provide molecular insights into the regulation of RPE cell
      proliferation and quiescence and may help us understand the mechanisms of normal
      RPE maintenance and of eye diseases associated with either RPE hyperproliferation
      or the lack of regenerative proliferation.

PMID- 29171180
TI  - The case for viral load testing in adolescents in resource-limited settings.
AB  - INTRODUCTION: The success of HIV treatment programmes globally has resulted in
      children with perinatally acquired HIV reaching adolescence in large numbers. The
      number of adolescents living with HIV is growing further due to persisting high
      HIV incidence rates among adolescents in low- and middle-income settings,
      particularly in sub-Saharan Africa. Although expanding access to HIV viral load
      monitoring is necessary to achieve the 90-90-90 targets across the HIV care
      continuum, implementation is incomplete. We discuss the rationale for
      prioritizing viral load monitoring among adolescents and the associated
      challenges. DISCUSSION: Adolescents with HIV are a complex group to treat
      successfully due to extensive exposure to antiretroviral therapy for those with
      perinatally acquired HIV and the challenges in sustained medication adherence in
      this age group. Given the high risk of treatment failure among adolescents and
      the limited drug regimens available in limited resource settings, HIV viral load
      monitoring in adolescents could prevent unnecessary and costly switches to second
      line therapy in virologically suppressed adolescents. Because adolescents living
      with HIV may be heavily treatment experienced, have suboptimal treatment
      adherence, or may be on second or even third-line therapy, viral load testing
      would allow clinicians to make informed decisions about increased counselling and
      support for adolescents together with the need to maintain or switch therapeutic
      regimens. CONCLUSIONS: Given scarce resources, prioritization of viral load
      testing among groups with a high risk of virological failure may be required.
      Adolescents have disproportionately high rates of virological failure, and
      targeting this age group for viral load monitoring may provide valuable lessons
      to inform broader scale-up.

PMID- 29171182
TI  - Acid hydrolysis reveals a low but constant level of pheomelanin in human black to
      brown hair.
AB  - We previously reported a constant ratio of the benzothiazole pheomelanin marker
      thiazole-2,4,5-tricarboxylic acid (TTCA) to the eumelanin marker pyrrole-2,3,5
      tricarboxylic acid (PTCA) in eumelanic, black human hair. A constant level (20%
      25%) of benzothiazole-type pheomelanin was recently demonstrated in human skin
      with varying concentrations of melanin. Therefore, in this study, we aimed to
      investigate the origin of pheomelanin markers in black to brown human hair by
      developing a method to remove protein components from hair by heating with 6 M
      HCl at 110 degrees C for 16 hr. For comparison, synthetic melanins were prepared
      by oxidizing mixtures of varying ratios of dopa and cysteine with tyrosinase.
      Hair melanins and synthetic melanins were subjected to acid hydrolysis followed
      by alkaline H2 O2 oxidation. The results show that the hydrolysis leads to
      decarboxylation of the 5,6-di-hydroxyindole-2-carboxylic acid moiety in eumelanin
      and the benzothiazole moiety in pheomelanin and that eumelanic human hair
      contains 11%-17% benzothiazole-type pheomelanin.

PMID- 29171183
TI  - Cause-specific mortality in HPV+ and HPV- oropharyngeal cancer patients: insights
      from a population-based cohort.
AB  - Identifying the causes of death in head and neck cancer patients can optimize
      follow-up and therapeutic strategies, but studies in oropharyngeal squamous cell
      carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause
      specific mortality in a population-based cohort of patients with OPSCC. Patients
      who had been diagnosed with OPSCC (n = 1541) between 2000 and 2014 in eastern
      Denmark were included in the study. Causes of death were collected through
      medical files and the Danish National Cause of Death registry. Deaths were
      grouped as (1) primary oropharyngeal cancer, (2) secondary malignancies, (3)
      cardiovascular and pulmonary disease, or (4) other/unspecified. The cumulative
      incidence of death and specific causes of death were determined using risk
      analysis. At follow-up, 723 (47.5%) patients had died. The median time to and
      cause of death were determined: oropharyngeal cancer (n = 432; 1.00 year),
      secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes
      (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16
      status was the strongest predictor of improved survival across all causes of
      death. The only cause of death to decrease in incidence over the 2 years after
      treatment was death from OPSCC. HPV/p16 positivity was an independent factor for
      improved survival across all causes of death in patients with OPSCC. In addition,
      both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year
      mortality rates. Implementing secondary screening and prevention strategies for
      late toxicity and mortality are major goals in managing the treatment of these
      patients.

PMID- 29171184
TI  - Structural malformations of the brain, eye, and pituitary gland in PHACE
      syndrome.
AB  - PHACE syndrome is the association of segmental facial hemangiomas with congenital
      arterial, brain, cardiac, and ocular anomalies. Structural brain malformations
      affect 41-52% of PHACE patients and can be associated with focal neurologic
      deficits, developmental delays, and/or intellectual disability. To better
      characterize the spectrum of structural brain and other intracranial anomalies in
      PHACE syndrome, MRI scans of the head/neck were retrospectively reviewed in 55
      patients from the PHACE Syndrome International Clinical Registry and Genetic
      Repository. All registry patients with a diagnosis of definite PHACE syndrome who
      had MRI scans of satisfactory quality were included. Of 55 patients, 34 (62%)
      demonstrated >=1 non-vascular intracranial anomaly; structural brain
      malformations were present in 19 (35%). There was no difference in the prevalence
      of brain anomalies between genders. Brain anomalies were more likely in patients
      with S1 and/or S2 distribution of facial hemangioma. The most common structural
      brain defects were cerebellar hypoplasia (25%) and fourth ventricle abnormalities
      (13%). Dandy-Walker complex and malformations of cortical development were
      present in 9% and 7%, respectively. Extra-axial findings such as pituitary
      anomalies (18%) and intracranial hemangiomas (18%) were also observed. Six
      patients (11%) had anomalies of the globes or optic nerve/chiasm detectable on
      MRI. Brain malformations comprise a diverse group of structural developmental
      anomalies that are common in patients with PHACE syndrome. Along with brain
      malformations, numerous abnormalities of the pituitary, meninges, and globes were
      observed, highlighting the need for careful radiologic assessment of these
      structures in the neuroimaging workup for PHACE syndrome.

PMID- 29171185
TI  - Low-grade inflammation and muscular fitness on insulin resistance in adolescents:
      Results from LabMed Physical Activity Study.
AB  - BACKGROUND: Low muscular fitness (MF) and low-grade inflammation has been linked
      to insulin resistance (IR). OBJECTIVE: To evaluate the associations between MF
      and a clustered score of inflammatory biomarkers on IR and to investigate the
      combined impact of MF and inflammation on IR in adolescents. METHODS: This is a
      cross-sectional analysis with 529 adolescents (267 girls) aged 12 to 18 years.
      Pubertal stage, socioeconomic status, adherence to the Mediterranean diet,
      cardiorespiratory fitness, and waist circumference were assessed. Standing long
      jump and isometric handgrip dynamometry were used as indicators of MF. Continuous
      score of clustered inflammatory biomarkers (InflaScore) (sum of Z-scores of C
      reactive protein, C3, C4, fibrinogen, and leptin) and IR (homeostasis model
      assessment of insulin resistance [HOMA-IR] estimated from fasting serum insulin
      and glucose) were assessed. RESULTS: HOMA-IR and fasting insulin were positively
      associated with InflaScore and negatively associated with MF, independently of
      age, sex, pubertal stage, socioeconomic status, adherence to the Mediterranean
      diet, cardiorespiratory fitness, and waist circumference. Adolescents classified
      as High InflaScore/Unfit showed significantly higher HOMA-IR when compared than
      those with High InflaScore/Fit and those with Low InflaScore/Fit (F(3,519)  =
      4.761, P < .003), after adjustments for potential confounders. Unfit adolescents
      with high InflaScore had the highest odds of expressing high HOMA-IR (odds ratio,
      OR = 2.40, 95% confidence interval [CI]: 1.2-5.6) and insulin risk (2.53 95% CI,
      1.5-5.9) when compared to those of the Low InflaScore/Fit group, after
      adjustments for potential confounders. CONCLUSION: Higher levels of MF seem to
      minimize the deleterious effect of inflammation on IR.

PMID- 29171186
TI  - The mechanism of action of sodium-glucose co-transporter 2 inhibitors is similar
      to carbonic anhydrase inhibitors.

PMID- 29171187
TI  - The effect of allogeneic cardiac stem cells in left ventricular geometry and
      function in a rat model of myocardial infarction.
AB  - BACKGROUND: The development of heart failure after acute myocardial infarction
      (MI) was related to left ventricular (LV) pathological remodeling and
      dysfunction. Cardiac stem cells (CSCs) provided a new option to treat acute MI.
      This study was to investigate the effects of CSCs on structural and functional
      alteration in acute MI. METHODS: Acute MI was induced in 20 Sprague-Dawley rats
      by ligation of the left anterior descending coronary artery. Two weeks after MI,
      animals were randomized into CSCs or control group. LV geometry and function were
      echocardiographically measured at baseline, 2, 4, and 6 weeks after MI. After
      measuring hemodynamics at 6 weeks after MI, hearts were harvested for tracing
      CSCs stained by PKH26 and testing expression of VEGF-alpha/TGF-beta1 by RT-PCR
      and ELISA. RESULTS: Two weeks after MI, there were significant decreases in
      interventricular septal systolic and diastolic thickness (IVSTs/d), while
      increases in LV systolic and diastolic dimension (LVDs/d). Consequently, this
      contributed to decreases in ejection fraction (EF) and fractional shorting (FS).
      With the treatment of CSCs for 4 weeks, significant better ejection fraction (EF)
      and fractional shorting (FS) were achieved in CSCs group accompanied by the
      reduction in LV systole and diastole dimension (LVDs/d). Besides, a significant
      improvement in the maximal rate of LV pressure development and decline (peak
      +dP/dt and -dP/dt, respectively) was observed. Moreover, significantly higher
      VEGF-alpha was expressed in CSCs group rather than TGF-beta1. CONCLUSION: CSCs
      significantly prevented structural and functional deterioration after MI with
      increasing expression of VEGF-alpha.

PMID- 29171189
TI  - Synthetic lethality in DNA repair network: A novel avenue in targeted cancer
      therapy and combination therapeutics.
AB  - Synthetic lethality refers to a lethal phenotype that results from the
      simultaneous disruptions of two genes, while the disruption of either gene alone
      is viable. Many DNA double strand break repair (DSBR) genes have synthetic lethal
      relationships with oncogenes and tumor suppressor genes, which can be exploited
      for targeted cancer therapy, an approach referred to as combination therapy. DNA
      double-strand breaks (DSBs) are one of the most toxic lesions to a cell and can
      be repaired by non-homologous end joining (NHEJ) or homologous recombination
      (HR). HR and NHEJ genes are particularly attractive targets for cancer therapy
      because these genes have altered expression patterns in cancer cells when
      compared with normal cells and these genetic abnormalities can be targeted for
      selectively killing cancer cells. Here, we review recent advances in the
      development of small molecule inhibitors against HR and NHEJ genes to induce
      synthetic lethality and address the future directions and clinical relevance of
      this approach. (c) 2017 IUBMB Life, 69(12):929-937, 2017.

PMID- 29171190
TI  - Routine viral load monitoring in HIV-infected infants and children in low- and
      middle-income countries: challenges and opportunities.
AB  - INTRODUCTION: The objective of this commentary is to review considerations for
      implementing routine viral load (VL) monitoring programmes for HIV-infected
      infants and children living in low- and middle-income countries (LMIC). Since
      2013, the World Health Organization (WHO) guidelines recommend VL testing as the
      preferred monitoring approach for all individuals treated with ART in order to
      assess treatment response, detect treatment failure and determine the need to
      switch to a second-line regimen in a timely manner. More recently, WHO guidelines
      from 2016 identify HIV-infected infants and children as a priority group for
      routine VL monitoring. DISCUSSION: There are a number of reasons why HIV-infected
      infants and children should be prioritized for routine VL monitoring. Data from
      national VL monitoring programmes as well as systematic reviews and meta-analyses
      from LMIC indicate rates of viral suppression are lower for infants and children
      compared to adults. The number of antiretroviral drugs and palatable formulations
      suitable for young children are limited. In addition, emotional and developmental
      issues particular to children can make daily medication administration difficult
      and pose a challenge to adherence and achievement of sustained viral suppression.
      VL monitoring can be instrumental for identifying those in need of additional
      adherence support, reducing regimen switches and preserving treatment options.
      The needs of infants and children warrant consideration in all aspects of VL
      monitoring services. If capacity for paediatric venipuncture is not assured,
      platforms that accept dried blood spot specimens are necessary in order for
      infants and children to have equitable access. Healthcare systems also need to
      prepare to manage the substantial number of infants and children identified with
      elevated VL, including adherence interventions that are appropriate for children.
      Establishing robust systems to evaluate processes and outcomes of routine VL
      monitoring services and to support drug forecasting and supply management is
      essential to determine best practices for infants and children in LMIC.
      CONCLUSIONS: The particular concerns of HIV-infected infants and children warrant
      attention during all phases of planning and implementation of VL monitoring
      services. There are a number of key areas, including frequency of monitoring,
      blood specimen type and adherence challenges, where specific approaches tailored
      for infants and children may be required.

PMID- 29171191
TI  - Pre-Zika descriptive epidemiology of microcephaly in Texas, 2008-2012.
AB  - BACKGROUND: There are limited population-based studies on microcephaly. We
      characterized the epidemiology of microcephaly in Texas during a 5-year period
      (2008-2012), prior to the Zika epidemic in the Western hemisphere (2015). The
      associations of suspected risk factors were compared across four clearly defined
      case groups. METHODS: Data from the Texas Birth Defects Registry were used to
      calculate the prevalence of congenital microcephaly and crude and adjusted
      prevalence ratios using Poisson regression. Twelve maternal and infant factors
      were assessed across case groups, which included total (explained + unexplained),
      explained (e.g., syndromic), unexplained, and severe unexplained microcephaly
      (head circumference <3rd percentile). RESULTS: The birth prevalence for total and
      total severe microcephaly were 14.7 and 4.8 per 10,000 livebirths, respectively.
      For explained and unexplained cases, significantly elevated risks were noted for
      mothers who were older (35+), less educated (<=12 years), diabetic (pre-pregnancy
      or gestational), or had a preterm delivery. Unlike explained cases, however,
      mothers who were non-White or smoked had an increased risk for unexplained
      microcephaly. Furthermore, young maternal age (<20), multiparity, and higher BMI
      reduced the risk for unexplained microcephaly. For severe unexplained cases, the
      risk profile was similar to that for all unexplained cases-with the exception of
      null associations noted for diabetes and birth year. CONCLUSIONS: We found that
      risk patterns for microcephaly varied across case groupings. Risk factors
      included maternal race/ethnicity, age, and smoking during pregnancy. Among severe
      unexplained cases, notable positive associations were seen among mothers who were
      non-Hispanic Black or less educated, while inverse associations were noted for
      obesity.

PMID- 29171192
TI  - Selecting a viral load threshold for routine monitoring in resource-limited
      settings: optimizing individual health and population impact.

PMID- 29171194
TI  - Third-Person Self-Talk Reduces Ebola Worry and Risk Perception by Enhancing
      Rational Thinking.
AB  - BACKGROUND: During the fall of 2014, the threat of an Ebola outbreak gripped the
      United States (Poll, 8-12 October 2014; see Harvard School of Public Health &
      SSRS, 2014), creating a unique opportunity to advance basic knowledge concerning
      how emotion regulation works in consequential contexts and translate existing
      research in this area to inform public health and policy. METHOD: We addressed
      these issues by examining whether third-person self-talk, a simple technique that
      promotes emotion regulation, could nudge people into reasoning about Ebola more
      rationally. In all, 1,257 people from across the United States were asked to
      write about their feelings about Ebola using their name or I (i.e. third-person
      self-talk vs. first-person self-talk) as concerns about Ebola swelled (24 October
      2014-26 October 2014). RESULTS: Third-person self-talk led participants who
      scored high on Ebola worry at baseline to generate more fact-based reasons not to
      worry about Ebola, which predicted reductions in their Ebola worry and risk
      perception. These findings held when controlling for several theoretically
      relevant covariates, highlighting their robustness. CONCLUSION: These results
      demonstrate how a simple linguistic technique can enhance rational thinking and
      quell worry about a pressing public health threat.

PMID- 29171193
TI  - Returning HIV-1 viral load results to participant-selected health facilities in
      national Population-based HIV Impact Assessment (PHIA) household surveys in three
      sub-Saharan African Countries, 2015 to 2016.
AB  - INTRODUCTION: Logistical complexities of returning laboratory test results to
      participants have precluded most population-based HIV surveys conducted in sub
      Saharan Africa from doing so. For HIV positive participants, this presents a
      missed opportunity for engagement into clinical care and improvement in health
      outcomes. The Population-based HIV Impact Assessment (PHIA) surveys, which
      measure HIV incidence and the prevalence of viral load (VL) suppression in
      selected African countries, are returning VL results to health facilities
      specified by each HIV positive participant within eight weeks of collection. We
      describe the performance of the specimen and data management systems used to
      return VL results to PHIA participants in Zimbabwe, Malawi and Zambia. METHODS:
      Consenting participants underwent home-based counseling and HIV rapid testing as
      per national testing guidelines; all confirmed HIV positive participants had VL
      measured at a central laboratory on either the Roche CAP/CTM or Abbott m2000
      platform. On a bi-weekly basis, a dedicated data management team produced logs
      linking the VL test result with the participants' contact information and
      preferred health facility; project staff sent test results confidentially via
      project drivers, national courier systems, or electronically through an adapted
      short message service (SMS). Participants who provided cell phone numbers
      received SMS or phone call alerts regarding availability of VL results. RESULTS
      AND DISCUSSION: From 29,634 households across the three countries, 78,090 total
      participants 0 to 64 years in Zimbabwe and Malawi and 0 to 59 years in Zambia
      underwent blood draw and HIV testing. Of the 8391 total HIV positive participants
      identified, 8313 (99%) had VL tests performed and 8245 (99%) of these were
      returned to the selected health facilities. Of the 5979 VL results returned in
      Zimbabwe and Zambia, 85% were returned within the eight-week goal with a median
      turnaround time of 48 days (IQR: 33 to 61). In Malawi, where exact return dates
      were unavailable all 2266 returnable results reached the health facilities by 11
      weeks. CONCLUSIONS: The first three PHIA surveys returned the vast majority of VL
      results to each HIV positive participant's preferred health facility within the
      eight-week target. Even in the absence of national VL monitoring systems, a
      system to return VL results from a population-based survey is feasible, but it
      requires developing laboratory and data management systems and dedicated staff.
      These are likely important requirements to strengthen return of results systems
      in routine clinical care.

PMID- 29171195
TI  - The Dynamic Nature of Self-Assessed Health (SAH) as a Function of Negative and
      Positive Affects among Cardiac Patients.
AB  - BACKGROUND: Self-assessed health (SAH) predicts health outcomes above and beyond
      medical variables. One of the explanations for this robust finding is the
      sensitivity of SAH to changes in multiple aspects of health, including emotional
      factors. We assessed the dynamic nature of SAH by longitudinally examining the
      associations between initial and change levels of SAH and positive affect (PA)
      and negative affect (NA). METHODS: Participants were 138 cardiac patients
      undergoing coronary angioplasty. Self-report questionnaires measured SAH, PA, and
      NA, one day and one month after catheterisation. RESULTS: Means of SAH and NA did
      not change between measurement points, but PA decreased. Cross-lagged analysis
      indicated that the best model for representing the data included a path from
      affect at hospitalisation to SAH one month later; that is, lower NA (but not PA)
      at hospitalisation predicted higher SAH a month later. A latent change model
      analysis also revealed that NA (but not PA) at hospitalisation predicted changes
      in SAH (but SAH did not predict changes in negative or positive affect); and that
      increases in positive affect and decreases in negative affect were linked to
      increases in SAH. CONCLUSIONS: These findings highlight the importance of NA as
      an indicator of SAH and SAH change, and provide further insights into the
      dynamics of SAH in cardiac patients.

PMID- 29171196
TI  - Clinical and Subclinical Distress, Quality of Life, and Psychological Well-Being
      after Cardiac Rehabilitation.
AB  - BACKGROUND: The literature has outlined positive effects of cardiac
      rehabilitation (CR) on clinical psychological distress (DSM depression and
      anxiety) and quality of life (QoL). In cardiac settings, subclinical distress
      (subthreshold depressive and anxious symptomatology) and psychological well-being
      also showed relevant clinical implications. This research explored these
      psychological variables, their changes over time and cardiac course of CR
      patients. METHODS: Clinical and subclinical distress, QoL, and psychological well
      being were assessed in 108 consecutive patients undergoing CR, at baseline and up
      to 12 months after the program's completion. RESULTS: Of all patients, 25.9 per
      cent showed high distress with a DSM diagnosis, 31.5 per cent high distress
      without a DSM diagnosis, and 42.6 per cent low distress. Comparing these
      subgroups, worse QoL and psychological well-being were significantly linked not
      only to clinical but also to subclinical distress. After CR completion, a
      significant reduction in DSM diagnoses was observed, whereas there were no
      positive effects on subclinical distress, QoL, and well-being, or when they
      initially occurred, they were not long lasting. Moreover, only the subgroup with
      high distress without a DSM diagnosis was at greater risk for adverse cardiac
      outcomes, showing worse scores on items of contentment. CONCLUSIONS: These
      findings confirm data on clinical distress reduction after CR completion.
      However, a large amount of relevant subclinical distress remains and predicts
      adverse cardiac events.

PMID- 29171197
TI  - Socioeconomic Context as a Moderator in the Relationship between Body Mass Index
      and Depression in Europe.
AB  - BACKGROUND: Obesity and depression are two major health issues in contemporary
      societies. This study aims to address two fundamental questions: (1) what is the
      impact of macro-level adverse socioeconomic circumstances on depression? and (2)
      how do macro-level variations in the socioeconomic context affect the
      relationship between body mass index (BMI) and depression? METHODS: Data from the
      7th round of the European Social Survey were used, collected from a sample size
      of 37,623 participants and aggregated around a total of 20 countries. A random
      intercept multilevel model was constructed to study the variations in the
      relationship between depression and BMI. The contextual effect of risk of
      poverty, unemployment rate, and gross domestic product per capita were studied at
      the country level. RESULTS: First, both unemployment and poverty risk were found
      to be positively associated with depressive disorders. Second, the results show
      that a higher risk of poverty at the macro level may increase the effect of BMI
      on depression in European countries. CONCLUSION: The present study provides new
      evidence suggesting that the obesity-depression relationship will be, on average,
      stronger in countries with poor socioeconomic conditions. Therefore, adverse
      socioeconomic contextual conditions may increase depression associated with
      obesity.

PMID- 29171198
TI  - Ischemia-based Coronary Revascularization: Beyond Anatomy and Fractional Flow
      Reserve.
AB  - Treatment strategies for patients with coronary artery disease (CAD) should be
      based on objective evidence of inducible ischemia in the subtended myocardium to
      improve clinical outcomes, symptoms, and cost-effectiveness. Fractional flow
      reserve (FFR) is the most verified index to-date for invasively evaluating lesion
      specific myocardial ischemia. Favorable results from large clinical trials that
      applied FFR-guided percutaneous coronary intervention (PCI) prompted changes in
      coronary revascularization guidelines to emphasize the importance of this
      ischemia-based strategy using invasive coronary physiology. However, the
      frequency of functional evaluations is lacking in daily practice, and visual
      assessment still dominates treatment decisions in CAD patients. Despite recent
      efforts to integrate functional and anatomical assessments for coronary stenosis,
      there is considerable discordance between the 2 modalities, and the diagnostic
      accuracy of simple parameters obtained from current imaging tools is not
      satisfactory to determine functional significance. Although evidence that
      supports or justifies anatomy-guided PCI is more limited, and FFR-guided PCI is
      currently recommended, it is important to be aware of conditions and factors that
      influence FFR for accurate interpretation and application. In this article, we
      review the limitations of the current anatomy-derived evaluation of the
      functional significance of coronary stenosis, detail considerations for the
      clinical utility of FFR, and discuss the importance of an integrated physiologic
      approach to determine treatment strategies for CAD patients.

PMID- 29171199
TI  - Unroofed Coronary Sinus Atrial Septal Defect Misdiagnosed as Ostium Primum
      Defect.

PMID- 29171200
TI  - Clinical Characteristics of Korean Patients with Bicuspid Aortic Valve Who
      Underwent Aortic Valve Surgery.
AB  - BACKGROUND AND OBJECTIVES: Clinical data for Korean patients with bicuspid aortic
      valve (BAV) that underwent aortic valve (AV) surgery are currently limited.
      METHODS: Data for 1,160 consecutive adult BAV patients who underwent AV surgery
      from 2000 to 2014 in 4 tertiary referral centers were retrospectively analyzed. A
      standard case report form was used for clinical and echocardiographic parameters.
      RESULTS: Mean age at the time of AV surgery was 59+/-13 years. The most common
      cause of AV surgery was aortic stenosis (AS, 892 [77%]), followed by aortic
      regurgitation (AR, 199 [17%]), and infective endocarditis (69 [6%]). AS showed a
      skewed peak in the aged population and was the predominant cause of AV surgery
      (87%) in patients >=50 years of age, whereas AR (46%) and active infective
      endocarditis (19%) were more common in younger patients (p<0.001).
      Echocardiographic determination of the BAV phenotype revealed that fusion of the
      right coronary cusp (RCC) and left coronary cusp (LCC) was most common (622
      [53%]), followed by fusion of RCC and non-coronary cusp (NCC) (313 [27%]), and
      fusion of LCC and NCC (42 [4%]); the BAV phenotype could not be determined in the
      remaining 183 patients (16%). Fusion of RCC and LCC was more commonly observed in
      patients with AR than in those with AS (74% vs. 49%; p<0.001). CONCLUSION: BAV
      patients were characterized by distinct surgical indications according to their
      age. Possible associations between BAV phenotypes and surgical indications with
      potential impacts of ethnicity need to be tested in further studies.

PMID- 29171201
TI  - Carotid Artery Stenting.
AB  - Carotid artery stenosis is relatively common and is a significant cause of
      ischemic stroke, but carotid revascularization can reduce the risk of ischemic
      stroke in patients with significant symptomatic stenosis. Carotid endarterectomy
      has been and remains the gold standard treatment to reduce the risk of carotid
      artery stenosis. Carotid artery stenting (CAS) (or carotid artery stent
      implantation) is another method of carotid revascularization, which has developed
      rapidly over the last 30 years. To date, the frequency of use of CAS is
      increasing, and clinical outcomes are improving with technical advancements.
      However, the value of CAS remains unclear in patients with significant carotid
      artery stenosis. This review article discusses the basic concepts and procedural
      techniques involved in CAS.

PMID- 29171202
TI  - Advances in Intravascular Imaging: New Insights into the Vulnerable Plaque from
      Imaging Studies.
AB  - The term "vulnerable plaque" denotes the plaque characteristics that are
      susceptible to coronary thrombosis. Previous post-mortem studies proposed 3 major
      mechanisms of coronary thrombosis: plaque rupture, plaque erosion, and calcified
      nodules. Of those, characteristics of rupture-prone plaque have been extensively
      studied. Pathology studies have identified the features of rupture-prone plaque
      including thin fibrous cap, large necrotic core, expansive vessel remodeling,
      inflammation, and neovascularization. Intravascular imaging modalities have
      emerged as adjunctive tools of angiography to identify vulnerable plaques.
      Multiple devices have been introduced to catheterization laboratories to date,
      including intravascular ultrasound (IVUS), virtual-histology IVUS, optical
      coherence tomography (OCT), coronary angioscopy, and near-infrared spectroscopy.
      With the use of these modalities, our understanding of vulnerable plaque has
      rapidly grown over the past several decades. One of the goals of intravascular
      imaging is to better predict and prevent future coronary events, for which
      prospective observational data is still lacking. OCT delineates microstructures
      of plaques, whereas IVUS visualizes macroscopic vascular structures.
      Specifically, plaque erosion, which has been underestimated in clinical practice,
      is gaining an interest due to the potential of OCT to make an in vivo diagnosis.
      Another potential future avenue for intravascular imaging is its use to guide
      treatment. Feasibility of tailored therapy for acute coronary syndromes (ACS)
      guided by OCT is under investigation. If it is proven to be effective, it may
      potentially lead to major shift in the management of millions of patients with
      ACS every year.

PMID- 29171204
TI  - Longitudinal Stent-Strut Injury at the Distal End of a Newer-generation Drug
      eluting Stent.

PMID- 29171203
TI  - Association of Syntax Score II with Contrast-induced Nephropathy and Hemodialysis
      Requirement in Patients with ST Segment Elevation Myocardial Infarction
      Undergoing Primary Percutaneous Coronary Intervention.
AB  - BACKGROUND AND OBJECTIVES: Contrast-induced nephropathy (CIN) is a common
      complication of primary percutaneous coronary intervention (pPCI) and is
      associated with high mortality and morbidity and long hospital stay in patients
      with ST elevation myocardial infarction (STEMI). The Syntax Score (SS) has
      previously been studied in STEMI patients, and it was associated with increased
      CIN development and long-term mortality. This study investigates a possible
      relationship between CIN development and Syntax Score II (SSII) and compares SS
      and SSII by assessing CIN risk in STEMI patients treated with pPCI. METHODS: A
      total of 1,234 patients who underwent pPCI were divided into 2 groups according
      to CIN development. Patients with CIN were further divided into 2 groups
      according to whether or not they required hemodialysis. Reclassification tables,
      net reclassification improvement, and integrated discriminative improvement
      methods were used to assess the additive predictive value of SSII for predicting
      CIN. RESULTS: In the present study, 166 patients (13.5%) had CIN. Although both
      SS and SSII were significantly higher in CIN patients, only SSII was an
      independent predictor of CIN (odds ratio [OR], 1.031; 95% confidence interval
      [CI], 1.012-1.051; p<0.001) and hemodialysis requirement (OR, 1.078; 95% CI,
      1.046-1.078; p<0.001). When comparing SSII and SS in their ability to determine
      CIN risk, we found SSII to have a reclassification improvement of 27.59%
      (p<0.001) and an integrated discrimination improvement of 9.1% (p<0.001).
      CONCLUSIONS: The combination of clinical and anatomic variables can more
      accurately identify patients who are at high risk for CIN after pPCI. While SSII
      is harder to calculate than SS, it provides better prediction for CIN and
      hemodialysis requirement than SS.

PMID- 29171205
TI  - Factors Predicting Resistance to Intravenous Immunoglobulin Treatment and
      Coronary Artery Lesion in Patients with Kawasaki Disease: Analysis of the Korean
      Nationwide Multicenter Survey from 2012 to 2014.
AB  - BACKGROUND AND OBJECTIVES: Approximately 10-15% of children with Kawasaki disease
      (KD) do not respond to initial intravenous immunoglobulin (IVIG) and have higher
      risk for coronary artery lesion (CAL). The aim of this study was to identify
      predictive factors from laboratory findings in patients who do not respond to
      IVIG treatment and develop CAL from KD. METHODS: We retrospectively collected
      nationwide multicenter data from the Korean Society of Kawasaki Disease and
      included 5,151 patients with KD between 2012 and 2014 from 38 hospitals. RESULTS:
      Among 5,151 patients with KD, 524 patients belonged to the IVIG-resistant group.
      The patients in the IVIG-resistant group had a significantly higher serum N
      terminal pro-brain natriuretic peptide (NT-proBNP) level (1,573.91+/-3,166.46 vs.
      940.62+/-2,326.10 pg/mL; p<0.001) and a higher percentage of polymorphonuclear
      neutrophils (PMNs) (70.89+/-15.75% vs. 62.38+/-32.94%; p<0.001). Multivariate
      logistic regression analyses revealed that significantly increased PMN, NT
      proBNP, C-reactive protein (CRP), aspartate aminotransferase (AST), and alanine
      aminotransferase (ALT) were the predictors of IVIG resistance (p<0.05).
      Multivariate logistic regression analyses also showed that only CRP was
      associated with the risk of CAL (p<0.01), while PMN, NT-proBNP, AST, and ALT were
      not. CONCLUSIONS: Elevated PMN, serum NT-proBNP, CRP, AST, and ALT levels are
      significantly associated with IVIG resistance in patients with KD. Moreover,
      serum CRP is significantly increased in patients with KD with CAL.

PMID- 29171206
TI  - Extrinsic Compression of the Left Main Coronary Artery by a Huge Aortic Arch
      Aneurysm Mimicking Acute Coronary Syndrome.

PMID- 29171207
TI  - Formation and Transformation of Neointima after Drug-eluting Stent Implantation:
      Insights from Optical Coherence Tomographic Studies.
AB  - After coronary stent implantation, neointima formation resembles the wound
      healing process as it involves the sequential processes of inflammation,
      granulation, and remodeling. Because antiproliferative drugs and polymers of drug
      eluting stents (DESs) delay vascular healing compared with bare metal stents,
      fibrin deposition can remain long after stent implantation, or inflammation can
      be excessive. Delayed vascular healing can be associated with adverse clinical
      outcomes including DES thrombosis or restenosis, and poor endothelization of DES
      neointima can accelerate neoatherosclerotic change inside the neointima, further
      contributing to luminal restenosis or neointimal instability. Despite the lack of
      correlation between pathologic and optical coherence tomography (OCT) findings,
      OCT assessments of neointima under various circumstances can reveal vascular
      responses to stent therapy. Homogeneous, heterogeneous, and layered neointima
      patterns can be recognized by OCT and can change with time. Homogeneous neointima
      might be associated with better clinical outcomes after DES implantation, whereas
      non-homogeneous neointima or neoatherosclerotic change can be associated with
      poorer clinical outcomes. However, limited data are currently available, and
      further studies are required to comprehensively address these questions.

PMID- 29171208
TI  - Real-world Data and Recommended Dosage of Non-vitamin K Oral Anticoagulants for
      Korean Patients.
AB  - Regulatory approvals of non-vitamin K antagonist oral anticoagulants (NOACs) have
      been based on large randomized phase III trials evaluating dabigatran,
      rivaroxaban, apixaban, or edoxaban relative to warfarin for atrial fibrillation
      (AF). The results of the trials showed that all NOACs were at least non-inferior
      to warfarin in the prevention of stroke/thromboembolism and showed lower rates of
      intracranial bleeding than those associated with warfarin. However, the trials
      were designed differently, varied in the inclusion/exclusion criteria, and used
      either one dose or a low/high dose of the NOAC drug. Some of these differences
      have challenged the ability to directly compare various NOACs, and comparative
      data on effectiveness and intracranial bleeding are sparse in "real-world"
      patients. Real-world data complement data from large randomized phase III trials
      by providing new aspects of the "real-world" absolute risks of ischemic and
      hemorrhagic stroke associated with NOACs vs. warfarin. Moreover, "real-world"
      fragile patients might have been included (e.g., patients with increased risk of
      bleeding, liver disease, and chronic kidney disease), although these patients
      would be less represented in trials. This paper introduces recently published
      real-world data of NOACs and further suggests the recommended dosage of NOACs for
      Korean patients.

PMID- 29171209
TI  - Relationship between Pulmonary Artery Stiffness and Functional Capacity in
      Patients with Heart Failure with Reduced Ejection Fraction.
AB  - BACKGROUND AND OBJECTIVES: Functional capacity varies significantly among
      patients with heart failure with reduced ejection fraction (HFrEF), and it
      remains unclear why functional capacity is severely compromised in some patients
      with HFrEF while it is preserved in others. In this study, we aimed to evaluate
      the role of pulmonary artery stiffness (PAS) in the functional status of patients
      with HFrEF. METHODS: A total of 46 heart failure (HF) patients without overt
      pulmonary hypertension or right HF and 52 controls were enrolled in the study.
      PAS was assessed on parasternal short-axis view using pulsed-wave Doppler
      recording of pulmonary flow one centimeter distal to the pulmonic valve annulus
      at a speed of 100 mm/sec. PAS was calculated according to the following formula:
      the ratio of maximum flow velocity shift of pulmonary flow to pulmonary
      acceleration time. RESULTS: PAS was significantly increased in the HFrEF group
      compared to the control group (10.53+/-2.40 vs. 7.41+/-1.32, p<0.001). In sub
      group analysis of patients with HFrEF, PAS was significantly associated with the
      functional class of the patients. HFrEF patients with poor New York Heart
      Association (NYHA) functional capacity had higher PAS compared those with good
      functional capacity. In multivariate regression analysis, NYHA class was
      independently correlated with PAS. CONCLUSION: PAS is associated with functional
      status and should be taken into consideration as an underlying pathophysiological
      mechanism of dyspnea in patients with HFrEF.

PMID- 29171210
TI  - Pericardial-esophageal Fistula Complicating Atrial Fibrillation Ablation
      Successfully Resolved after Pericardial Drainage with Conservative Management.
AB  - A 40-year-old male patient underwent radiofrequency catheter ablation for
      symptomatic paroxysmal atrial fibrillation (AF). Although pulmonary vein (PV)
      isolation was successfully completed without acute complications, the patient
      began complaining of sustained retrosternal pain. Seventeen days after ablation,
      the patient visited the emergency room with fever and severe chest pain with
      pericarditis-like features. Chest computed tomography (CT) revealed clustered air
      bubbles in the pericardial space. Esophagography confirmed leakage of contrast
      agent into the pericardial space but not into the left atrium. While performing
      pericardiostomy, the operator confirmed the absence of active bleeding from the
      left atrium. Because there were no signs of left atrial-esophageal fistula, such
      as systemic embolization, conservative management based on strict fasting with
      fluids and antibiotic therapy was undertaken. Follow-up esophagography performed
      2 weeks later showed no more contrast agent leakage, and the patient was
      discharged without further incident.

PMID- 29171211
TI  - A Prospective Survey of Atrial Fibrillation Management for Real-world Guideline
      Adherence: COmparison study of Drugs for symptom control and complication
      prEvention of Atrial Fibrillation (CODE-AF) Registry.
AB  - BACKGROUND AND OBJECTIVES: The aging population is rapidly increasing, and atrial
      fibrillation (AF) is becoming a significant public health burden in Asia,
      including Korea. This study evaluated current treatment patterns and guideline
      adherence of AF treatment. METHODS: In a prospective observational registry
      (COmparison study of Drugs for symptom control and complication prEvention of
      Atrial Fibrillation [CODE-AF] registry), 6,275 patients with nonvalvular AF were
      consecutively enrolled between June 2016 and April 2017 from 10 tertiary
      hospitals in Korea. RESULTS: The AF type was paroxysmal, persistent, and
      permanent in 65.3%, 30.0%, and 2.9% of patients, respectively. Underlying
      structural heart disease was present in 11.9%. Mean CHA2DS2-VASc was 2.7+/-1.7.
      Oral anticoagulation (OAC), rate control, and rhythm control were used in 70.1%,
      53.9%, and 54.4% of patients, respectively. OAC was performed in 82.7% of
      patients with a high stroke risk. However, antithrombotic therapy was
      inadequately used in 53.4% of patients with a low stroke risk. For rate control
      in 192 patients with low ejection fraction (<40%), beta-blocker (65.6%), digoxin
      (5.2%), or both (19.3%) were adequately used in 90.1% of patients; however, a
      calcium channel blocker was inadequately used in 9.9%. A rhythm control strategy
      was chosen in 54.4% of patients. The prescribing rate of class Ic antiarrythmics,
      dronedarone, and sotalol was 16.9% of patients with low ejection fraction.
      CONCLUSION: This study shows how successfully guidelines can be applied in the
      real world. The nonadherence rate was 17.2%, 9.9%, and 22.4% for stroke
      prevention, rate control, and rhythm control, respectively.

PMID- 29171212
TI  - Plaque Characteristics and Ruptured Plaque Location according to Lesion Geometry
      in Culprit Lesions of ST-Segment Elevation Myocardial Infarction.
AB  - BACKGROUND AND OBJECTIVES: The correlations between plaque characteristics and
      plaque rupture location according to segmental lesion analysis have not been well
      defined. The aim of this study was to assess those characteristics of ST-segment
      elevation myocardial infarction (STEMI) culprit lesions according to segmental
      lesion geometry using virtual histology intravascular ultrasound (VH-IVUS).
      METHODS: Sixty single discrete lesions found in the left anterior descending
      (LAD) coronary arteries of 60 patients with STEMI were included. Each lesion was
      divided into 3 segments based on lumen area (LA) index, calculated by dividing
      the lesion LA by the reference LA. RESULTS: Among the 3 segments, the mid-segment
      showed the highest proportion of necrotic core (NC; proximal, mid-, and distal
      segments: 20.9+/-11.8%, 22.7+/-11.3%, and 17.5+/-11.2%, respectively, p=0.044).
      VH-IVUS-derived thin-cap fibroatheroma (VH-TCFA) was also more frequently found
      in the mid-segment than in proximal and distal segments (36.7%, 58.3%, and 16.7%,
      p<0.001). The mid-segment also showed the highest prevalence of plaque rupture
      (45.0%, 78.3% and 11.7%, p<0.001) and thrombus (61.7%, 95.0%, and 41.7%, p<0.001)
      compared to proximal or distal segments. When the lesions were divided into 2
      groups according to the median value (4.0 mm2) of minimum lumen area (MLA),
      plaque rupture at the distal segment was observed only in high MLA lesions (23.3%
      vs. 0.0%, p=0.011). CONCLUSION: Analysis of longitudinal lesion geometry using
      the LA index can be useful in evaluating plaque vulnerability and the incidence
      of plaque rupture and thrombus in STEMI patients.

PMID- 29171213
TI  - Extracorporeal Cardiopulmonary Resuscitation with Therapeutic Hypothermia for
      Prolonged Refractory In-hospital Cardiac Arrest.
AB  - BACKGROUND AND OBJECTIVES: We identified the impact of extracorporeal
      cardiopulmonary resuscitation (ECPR) followed by therapeutic hypothermia on
      survival and neurologic outcome in patients with prolonged refractory in-hospital
      cardiac arrest (IHCA). METHODS: We enrolled 16 adult patients who underwent ECPR
      followed by therapeutic hypothermia between July 2011 and December 2015, for
      IHCA. Survival at discharge and cerebral performance category (CPC) scale were
      evaluated. RESULTS: All patients received bystander cardiopulmonary resuscitation
      (CPR); the mean CPR time was 66.5+/-29.9 minutes, and the minimum value was 39
      minutes. Eight patients (50%) were discharged alive with favorable neurologic
      outcomes (CPC 1-2). The mean follow-up duration was 20.1+/-24.3 months, and most
      deaths occurred within 21 days after ECPR; thereafter, no deaths occurred within
      one year after the procedure. CONCLUSION: ECPR followed by therapeutic
      hypothermia could be considered in prolonged refractory IHCA if bystander
      initiated conventional CPR is performed.

PMID- 29171215
TI  - Gaps between Real-world Practice and Guidelines in Managing Patients with Atrial
      Fibrillation in Korea.

PMID- 29171216
TI  - Nd:YAG laser combined with gold nanorods for potential application in port-wine
      stains: an in vivo study.
AB  - Neodymium:yttrium aluminum garnet (Nd:YAG) lasers exhibit considerable potential
      for treating deeply buried port-wine stains. However, the application of Nd:YAG
      laser is limited by its weak absorption to blood. This in vivo study tested the
      efficacy and safety of utilizing thiol-terminated methoxypolyethylene glycol
      modified gold nanorods (PEG-GNRs) to enhance the absorption of Nd:YAG laser to
      blood. Mouse mesentery and dorsal skinfold chamber (DSC) model were prepared to
      analyze the thermal responses of a single venule without anatomic structures, as
      well as blood vessels in the complex structure of the skin, to laser light. After
      the injection of 0.44 mg of PEG-GNRs, the required threshold density of laser
      energy for blood coagulation and complete vasoconstriction decreased from 24 to
      18  J/cm2 in the mesentery model and from 36 to 31  J/cm2 in the DSC model. The
      laser pulse required for blood coagulation and complete vasoconstriction
      decreased by 67.75% and 62.25% on average in the mesentery model and by 67.55%
      and 54.45% on average in the DSC model. Histological and histochemical results
      confirmed that PEG-GNRs are nontoxic in the entire mouse life span. Therefore,
      combining PEG-GNRs with Nd:YAG laser may be effective and safe for inducing an
      obvious thermal response of blood vessels under low energy density and minimal
      pulse conditions.

PMID- 29171214
TI  - Bioresorbable Vascular Scaffold Korean Expert Panel Report.
AB  - Bioresorbable vascular scaffold (BRS) is an innovative device that provides
      structural support and drug release to prevent early recoil or restenosis, and
      then degrades into nontoxic compounds to avoid late complications related with
      metallic drug-eluting stents (DESs). BRS has several putative advantages.
      However, recent randomized trials and registry studies raised clinical concerns
      about the safety and efficacy of first generation BRS. In addition, the general
      guidance for the optimal practice with BRS has not been suggested due to limited
      long-term clinical data in Korea. To address the safety and efficacy of BRS, we
      reviewed the clinical evidence of BRS implantation, and suggested the appropriate
      criteria for patient and lesion selection, scaffold implantation technique, and
      management.

PMID- 29171217
TI  - [Influence factors of hepatotoxicity of traditional Chinese medicine preparation
      products based on multidimensional structure dynamic process].
AB  - Traditional Chinese medicine (TCM) products are the finished products by adopting
      certain preparation processes according to the profile of the herbs, with Chinese
      herbs or decoction pieces as the raw materials.Among their adverse reactions to
      the organs, hepatotoxicity can not be ignored. As a new stage of quality control
      in TCM, dynamic quality control system of the multidemensional structure process
      emphasized on the research of the effectiveness and safety, focused on the
      pretreatment, preparation process,dosage forms and drug delivery methods to
      control the quality of TCM preparation products and reduce the generation of
      hepatotoxicity.In this paper, we will start from these factors to discuss the
      causes of hepatotoxicity underlying drug products and hope to provide the
      reference for developing low toxicity and high quality modern Chinese medicine
      products.

PMID- 29171218
TI  - [Discussion on influence factors, mechanism and traditional Chinese medicine
      pathogenesis of idiosyncratic drug-induced liver injury].
AB  - Idiosyncratic drug-induced liver injury (IDILI) is a kind of unique adverse drug
      reaction with relative high morbidity compared with other idiosyncratic diseases.
      Its occurrence, however, has nothing to do with pharmacological effects and
      clinical dosage of drugs administered, and only a small number of susceptible
      individuals will suffer from it. Especially to deserve to be mentioned, the
      proportion of TCM-induced IDILI showed an ascending trend year by year. So in
      this article, the author has reviewed some facts related with TCM-induced IDILI,
      including the predisposing causes and occurrence mechanism, and tries to provide
      reference for the prevention, diagnosis and treatment of TCM-induced IDILI
      through the analysis of characteristics and research status of TCM-induced IDILI
      and exploration of the internal relationship between Chinese medicine
      constitution type and IDILI.

PMID- 29171219
TI  - [Study on attenuating hepatotoxicity of Tripterygium wilfordii through
      compatibility of traditional Chinese medicine compound].
AB  - With the deepening of the study of toxicology of traditional Chinese medicine,
      the mechanism of hepatotoxicity caused by Tripterygium wilfordii has been
      gradually revealed. As one of the characteristics of traditional Chinese
      medicine, Chinese medicine compatibility show its more reasonable and scientific
      effect in terms of reducing toxicity. In this paper, the author summarizes the
      research on the basis and mechanism of toxic substances in T. wilfordii, and sum
      up the compatibility of traditional Chinese medicine (preparation) to reduce its
      role of hepatotoxicity, so as to provide reference for the rationality and safety
      in clinical application of T. wilfordii, thereby reducing liver adverse
      reactions.

PMID- 29171220
TI  - [Influence factors for hepatotoxicity of traditional Chinese medicine
      preparations].
AB  - Traditional Chinese medicine(TCM) preparation is one of the most important
      aspects in the development and quality control of traditional Chinese medicine,
      and its security problem becomes more and more serious. It is worthy to note that
      the liver, as the main drug metabolic organ, bears the brunt of the damage caused
      by TCM preparations. In this paper, the author attempts to explore the
      relationship between TCM preparations and hepatotoxicity based on the processing
      chains from crude drugs to the end product. Besides, the author hopes to clarify
      the underlying mechanism of hepatotoxicity of TCM preparations and provide basis
      and guidance for the quality control and rational clinical use of the
      preparations as well as the development of modern TCM preparations with high
      quality and low toxicity.

PMID- 29171221
TI  - [Advances on nanoparticles-tagged visual test strips for the rapid detection of
      pesticides].
AB  - The residue of the pesticides affects seriously the quality and safety of
      traditional Chinese medicine. Pesticide residue has caused ever-growing attention
      of people at home and abroad. Rapid detection techniques used for rapid screening
      of pesticide residues have expanded in a fast progress. As one of the fast
      development methods of rapid detection, visualization test strip based on
      nanoparticle has received much concern in recent years. This article focused on
      the classification of detection test strips and key factors on the fabrication of
      nanoparticle-based visualization test strips used in small molecule pesticides.
      Moreover, a wide application of nanoparticles-tagged test strips on pesticide
      residue was reviewed including single residue detection, multi residue detection,
      as well as quantitative analysis. Finally, the future application of visual test
      strip for detecting of pesticide residues in traditional Chinese medicine was
      forecasted, intending to provide the reference for rapid detection techniques on
      pesticide residues screening in herbal medicine industry.

PMID- 29171222
TI  - [Molecular regulative mechanisms of aging and interventional effects of Chinese
      herbal medicine].
AB  - Aging is a gradual process during the loss of functions in cells,organs and
      tissues by time. The molecular mechanisms of aging-related theories include the
      classical ones such as telomere,oxygen radical and nonenzymatic glycosylation,as
      well as the newly proposed ones such as DNA methylation,mitochondrial DNA
      (mtDNA)and autophagy. The latest study showed the anti-aging effect of autophagy
      in hematopoietic stem cells. In recent years,based on the molecular regulative
      mechanisms of aging,a number of the promising anti-aging drugs have been
      found,including nicotinamide mononucleotide(NMN)and FOXO4-DRI,a peptide of anti
      aging. In addition,there are many new discoveries in the field of plant
      extracts,in which,the extracts from Chinese herbal medicine(CHM),some single CHMs
      and the classical prescriptions of CHM,represented by curcumin and
      resveratrol,have the partial anti-aging effects by regulating the molecular
      mechanisms of aging both in vivo and in vitro. In brief,developing or exploring
      anti-aging drugs,especially the natural drugs,is one of the main development
      directions in the field of anti-aging research in the basis of the molecular
      regulative mechanisms of aging.

PMID- 29171223
TI  - [Recent advances on pericytes in microvascular dysfunction and traditional
      Chinese medicine prevention].
AB  - Pericytesis a kind of widespread vascular mural cells embedded within the
      vascular basement membrane of blood microvessels, constituting the barrier of
      capillaries and tissue spaces together with endothelial cells. Pericytes
      communicate with microvascular endothelial cells through cell connections or
      paracrine signals, playing an important role in important physiological processes
      such as blood flow, vascular permeability and vascular formation. Pericytes
      dysfunction may participate in some microvascular dysfunction, and also mediate
      pathological repair process, therefore pericytes attracted more and more
      attention. Traditional Chinese medicine suggests that microvascular dysfunction
      belongs to the collaterals disease; Qi stagnation and blood stasis in collaterals
      result in function imbalance of internal organs. Traditional Chinese medicine
      (TCM) has shown effects on pericytes in microvascular dysfunction, for example qi
      reinforcing blood-circulation activating medicines can reduce the damage of
      retinal pericytes in diabetic retinopathy. However, there are some limitations of
      research fields, inaccuracy of research techniques and methods, and lack of
      mechanism elaboration depth in the study of microvascular lesion pericytes. This
      paper reviewed the biological characteristics of pericytes and pericytes in
      microvascular dysfunction, as well as the intervention study of TCM on pericytes.
      The article aims to provide reference for the research of pericytes in
      microvascular dysfunction and the TCM study on pericytes.

PMID- 29171224
TI  - [Study on ecological suitability regionalization of Corni Fructus based on Maxent
      and ArcGIS model].
AB  - Through planting regionalization the scientific basis for planting area of high
      quality medicinal materials was predicted. Through interview investigation and
      field survey, the distribution information of Corni Fructus in China was
      collected,and 89 sampling point from 14 producing areas were collected. Climate
      and topography of Corni Fructus were analyzed, the ecological adaptability of
      study was conducted based on ArcGIS and Maxent. Different suitability grade at
      potential areas and regionalization map were formulated. There are nine
      ecological factors affecting the growth of Corni Fructus, for example
      precipitation in November and March and vegetation type. The results showed that
      the most suitable habitats are Henan, Shaanxi, Zhejiang, Chongqing, Hubei,
      Sichuan, Anhui, Hunan and Shandong province. Using the spatial analysis
      method,the study not only illustrates the most suitable for the surroundings of
      Corni Fructus,but also provides a scientific reference for wild resource tending,
      introduction and cultivation, and artificial planting base and directing
      production layout.

PMID- 29171225
TI  - [Effects of cultivation environments on Dendrobium catenatum].
AB  - The study was aimed to clarify the effect of three cultivation environments on
      the growth and metabolism of Dendrobium catenatum C13 group. There were three
      different cultivation conditions including rock epiphytic cultivation, pear
      epiphytic cultivation and pot cultivation. Morphological characteristics and
      agronomic characters of D. catenatum were observed and measured. Microstructure,
      contents of polysaccharide and alcohol-soluble extracts were measured by paraffin
      section method, phenol-sulfuric acid method and hot-dip method, respectively. The
      result showed that the cultivation environment significantly affected the growth
      of D. catenatum, the leaves of D. catenatum that cultivated on the rock and pear
      were sparse and small, the stems were short and purple and the root system was
      developed. Compare with potted cultivation, D. catenatum from rock epiphytic
      cultivation and pear epiphytic cultivation showed the following characteristics
      in the microstructure: the upper epidermis became thicker, the epidermal hair in
      the epidermis became denser, stomatal showed smaller and denser, the cell wall of
      exodermis, endoderm and medulla became thicker, the cell of velamen, exodermis,
      endoderm and medulla were smaller and arranged more closely, but the cultivation
      environment did not produce specific tissue structure, mainly changed in the
      structural parameters of size and quantity. The growth environments also
      influenced contents of polysaccharides and alcohol-soluble extracts. The dontents
      of polysaccharides and alcohol-soluble extracts in D. catenatum from rock
      epiphytic were the highest, reached 37.34% and 11.66%, the second was pear
      epiphytic, both higher than pot cultivation, alcohol-soluble extracts contents in
      D. catenatum from rock epiphytic are more complex, which shows that rock
      epiphytic is conducive to the accumulation of secondary metabolites in D.
      catenatum.

PMID- 29171226
TI  - [Genetic relationship and population genetic diversity of Epimedium pubescens and
      its related species based on ISSR and non-glandular hair characteristic].
AB  - In this study, 128 individuals form 14 Epimedium pubescens populations and 1 E.
      stellulatum population were analyzed by ISSR marker. The data were calculated by
      POPGENE software and clustered by UPGMA method. Optical microscope was used to
      observe the main types of the non-glandular hairs and their characteristics in
      each population. It is found that the following conclusions: Non-glandular hairs
      can be divided into five morphological categories, long straight pubescent, curly
      pubescent, appressed curly pubescent, pseudo short appressed hairs and long
      appressed. Eight primers were screening and a total of 94 bands were detected in
      ISSR, among which 90 were polymorphic bands. Based on the results of ISSR cluster
      analysis, 15 populations were divided into 3 clades. E. stellulatum populations
      should be incorporated into the E. pubescens or as avariety under E. pubescens
      not be independent and as it has no separate phylogenetic branch for a cluster.
      The genetic relationship among the populations of E. pubescens was closely
      related with its geographical distribution and non-glandular hair features. But
      there were also some inconsistency, which provided a good hint for the further
      study on the interspecific relationship and natural speciation manner of
      Epimedium species. Population diversity analysis showed Nm=0.354 4, Nei's=0.585
      2. It was showed that E. pubescens has high genetic diversity among populations,
      for which the main reason was probably the high inbreeding rate and the small
      range of seed dispersal.

PMID- 29171227
TI  - [Silkworm excrement bacterial communities diversity in different instars based on
      16S rDNA sequence analysis].
AB  - This paper investigated the diversity of the silkworm excrement bacterial
      communities in different ages before and after drying, aiming to clarify the
      differences of bacterial communities in composition and bacterial abundance and
      the influences of drying treatment, and provide scientific basis for the efficacy
      of scientific connotation and utilization of silkworm excrement. High-throughput
      sequencing technique was used to measure the sequence of 16S rDNA-V4 variable
      region of bacteria in silkworm excrement. QIIME, Mothur and PICRUSt software
      programs were employed to sort and calculate the number of sequences and
      operational taxonomic units (OTUs) for each sample. Thereafter, the abundance,
      distribution, alpha diversity index of species, beta diversity and bacterial
      communities diversity among different sample groups and predicted the bacterial
      gene functions were analyzed. In this study, the numbers of effective sequences
      for six samples were 259 250; the rarefaction curves showed a sufficient
      sequencing depth, and the number of OTUs was close to saturation. The bacteria in
      silkworm excrement belonged to the following five phylums: Proteobacteria
      (89.3%), Actinobacteria (5.0%), Firmicutes (4.4%), Bacteroidetes (1.1%) and
      Cyanobacteria (0.2%). The dominant specie was Cyanobacteria of the total bacteria
      identified, respectively. The abundances and diversities of the silkworm
      excrement bacterial communities have been reduced after drying treatment,
      especially the silkworm excrement of the fifth instar. PICRUSt analysis was
      performed to show that abundance of the functional genes such as membrane
      transport, carbohydrate metabolism, amino acid metabolism, lipid metabolism,
      nucleotide metabolism, cellular processes and signaling were relatively high. The
      result showed that the drying treatment could decreased the species and numbers
      of pathogenic bacteria in silkworm excrement obviously and improve the quality of
      medicinal materials. Compared with the lower ages, silkworm excrement of fifth
      instar seems like to be more suitable for use in medicine. Illumina MiSeq high
      throughput sequencing system provides a more accurate and scientific data
      resource for the study of bacteria in silkworm excrement.

PMID- 29171228
TI  - [Molecular cloning, bacterial expression analysis and functional characterization
      of pathogenesis-related PR10-2 gene in Panax notoginseng].
AB  - Base on the transcriptome analysis and RT-PCR techniques,a pathogenesis-related
      protein 10 gene was isolated from Panax notoginseng root and named as PnPR10-2.
      Bioinformatics and phylogenetic trees analysis revealed that open reading frame
      (ORF) of PnPR10-2 was 465 bp in length,encoding 154 amino acids,containing one
      typical conserved domain of pathogenesis related protein Bet v I family, and
      showed high similarity with that from P. ginseng. The recombinant expressed
      plasmid pET32a(+)-PnPR10-2 was expressed in Escherichia coli BL21. The expression
      conditions were optimized and it could be expressed well in soluble and inclusion
      body protein. Purified PnPR10-2 recombinant protein from the supernatant of cells
      was used to analysis the pathogen resistance activity by paper method. The
      purified recombinant protein could inhibit typical root rot disease pathogen
      (Fusarium solani and Cylindrocarpon destructans)growth evidently, we conjecture
      that PnPR10-2 may participated in defense response of P. notoginseng resistance
      to root rot disease pathogen.

PMID- 29171229
TI  - [Dynamic variation of components in exocarp of Juglans mandshurica with browning
      based on UPLC-Q-TOF/MS].
AB  - To analyze the dynamic changes in components in exocarp of Juglans mandshurica at
      different browning periods. Twenty-six batches of exocarp of J. mandshurica
      samples from thirteen browning periods were assessed by UPLC-Q-TOF-MS/MS. The
      formula of different compounds were determined by accurate mass and isotopic
      abundance ratio from target screening function of Peakview 2.0/masterview1.0
      software. Then their structures were determined by analysis of MS/MS fragment or
      comparison with standard substances and references. The contents of chemical
      components were changed significantly in different browning periods and twenty
      five compounds were identified or inferred. Of the 13 naphthoquinone compounds,
      the contents of 6 compounds with similar parent nucleus as juglone and 3
      naphthoquinone glycosides compounds were decreased significantly, and 4
      naphthoquinone derivatives such as regiolone were produced; the contents of four
      flavones and two phenolic acids compounds were decreased significantly; and the
      contents of 6 diarylheptanoids compounds were increased significantly. UPLC-Q
      TOF/MS method can be used to identify and analyze the chemical constituents from
      exocarp of J. mandshurica rapidly and accurately, and analyze the rules of
      dynamic changes, to reveal the browning of Chinese medicinal materials and its
      effects on compositions of fruits and vegetables.

PMID- 29171230
TI  - [Preparation and in vitro evaluation of rhein-loaded PEG-PCL-PEI nanoparticles].
AB  - This study was aimed to synthesize the polyethyleneglycol-polycaprolactone
      polyethyleneimine (PEG-PCL-PEI) three block polymer material, prepareRhein (RH)
      loaded PEG-PCL-PEI nanoparticles(PPP-RH-NPS), and then evaluate their physical
      and chemical properties and biological characteristics in vitro. PEG-PCL-PEI
      polymer was obtained by adopting thering-opening polymerization and Michael
      addition reaction, and their physical and chemical properties were analyzed by
      using NMR and gel permeation chromatography. PEG-PCL-PEI was then used as the
      carriers to prepare PPP-RH-NPS by applying spontaneous emulsification solvent
      diffusion method. The results showed that molecular weight of PEG-PCL-PEI polymer
      was 9.5*103, and critical micelle concentration was 0.723 mmol*L-1. PPP-RH-NPS
      had pale yellow, opalescence faade, round and smooth without aggregation, formed
      of (118.3+/-3.6) nm in particle size with PDI of (0.19+/-0.08), Zeta potential of
      (6.3+/-1.5) mV, entrapment efficiency of (93.64+/-5.28)%, and drug loading of
      (8.57+/-0.53)%. The accumulative release percentage of PPP-RH-NPS was 75.92% in
      48h, and the release profiles in PBS conformed to the Higuchi equation: Q=0.121
      6t1/2+0.069 5 (R2=0.887 4), presenting slow release characteristics. Within the
      scope of the 0-0.05 mmol*L-1, the nanoparticles had no obvious hemolysis on
      rabbit red blood cells and toxicity on HK-2 cells. In the investigation of uptake
      efficiency by flow cytometry, nanoparticles can be absorbed into cells quickly
      and internalized within 30 minutes fully, with a high uptake efficiency. In
      confocal laser scanning microscope observation, the nanoparticles can escape from
      lysosome into cytoplasm. Herein, this study synthesized the PEG-PCL-PEI polymer
      and prepared PPP-RH-NPS successfully; the nanoparticles showed uniform particle
      size, higher encapsulation efficiency and drug-loading rate, slow release
      characteristics, quick uptake and internalization, lysosome escape property and
      good biocompatibility. PPP-RH-NPS will be a promising pharmaceutical formulation
      for further development.

PMID- 29171231
TI  - [Bioactivity-guided isolation of anti-angiotensin converting enzyme constituents
      from Trichosanthis Pericarpium].
AB  - To isolate the anti-angiotensin converting enzyme (ACE) constituents from
      Trichosanthis Pericarpium based on bioactivity-guided separation. Trichosanthis
      Pericarpium was extracted with boiling water and precipitated by ethanol, then
      its supernatant was collected and dialyzed. The retentate of the fractions above
      1 000 was lyophilized to obtain GLP, which was then successively separated by
      DEAE Sepharose fast flow anion-exchange and Superdex-75 gel permeation
      chromatographic steps to achieve GLP-1-1. A combination of HPGPC, monosaccharide
      compositions determination and ACE inhibitory activity studies was performed to
      investigate the structure and bioactivity. The results showed that an anti
      angiotensin converting enzyme oligosaccharide, GLP-1-1, was obtained from
      Trichosanthis Pericarpium based on activity tracking, whose average molecular
      weight was estimated to 1 367; mainly composed of arabinose, mannose, and glucose
      at a ratio of 0.2?4.3?10.0. GLP-1-1 showed potent anti-angiotensin converting
      enzyme effect with the IC50of (113.4+/-8.6) mg*L-1. In this study, an
      oligosaccharide with anti-angiotensin converting enzyme effect was isolated from
      Trichosanthis Pericarpium, which could lay the foundation for the substance basis
      study of Trichosanthis Pericarpium.

PMID- 29171232
TI  - [Process of gallnut suppository preparation].
AB  - The main objective was to research the process of gallnut suppository preparation
      with its water extract as the main drug, and evaluate its irritation to rectal
      mucosa. gallnut extract was obtained by decocting method, and its suppository
      preparation was obtained by fusion method with semi-synthetic aliphatic esters
      and rose flower oil as the matrix. Weight difference and in vitro melting time
      limit of the suppository were assayed and UV-Vis was used to determine the
      contents of polyphenols, tannin and saccharide. The irritation to colon mucosa
      was evaluated after successive administration of 14 days to New Zealand white
      rabbits. Finally, the prescription compositions were determined: semi-synthetic
      aliphatic esters and rose flower oil with the ratio of 2:1 as the proper matrix,
      with the drug loading of 54%. The prepared suppository was brown, conical and
      smooth. The weight difference was (1.43+/-0.03) g, with an average melting time
      limit of (17+/-2) min. The Contents of Polyphenols, tannic and polysaccharide
      were 332.4, 245.0, 3.3 mg*g-1 respectively in each suppository. The results also
      showed that the continuous administration had no irritation to rectal mucosa. It
      can be concluded that the suppository was an acceptable administrate form, whose
      preparation process was easily controlled, and with no irritation to rectum
      mucosa.

PMID- 29171233
TI  - [A new napthalenone from roots of Rumex nepalensis].
AB  - A new napthalenone, rumexone A (1), was isolated from the roots of Rumex
      nepalensis. The structure of 1 was elucidated by extensive spectroscopic
      analyses, including 1D and 2D NMR spectra and MS data. Its cytotoxic effect was
      evaluated using four clinically relevant human cancer cell lines, gastric
      carcinoma SGC7901, breast carcinoma MDA-MB-231, lung carcinoma A549, and
      hepatocellular carcinoma HepG2.

PMID- 29171234
TI  - [Sesquiterpenes from Artabotrys hongkongensis].
AB  - The chemical consituents from Artabotrys hongkongensis were separated and
      purified by column chromatographies with silica gel, Sephadex LH-20, ODS and RP
      HPLC. The structures of the isolated compounds were identified on the basis of
      physicochemical properties and spectroscopic analysis, as well as comparisons
      with the data reported in the literature. As a result, 16 sesquiterpenes were
      isolated and elucidated as blumenol A (1), 4, 5-dihydroblumenol A (2), (6R, 9S)-3
      oxo-a-ionol (3), 3-hydroxy-beta-ionone (4), dehydrovomifoliol (5), (3R, 6R, 7E) 
      3-hydroxy-4, 7-megastigmadien-9-one (6), sarmentol F (7), 10-oxo-isodauc-3-en-15
      oic acid (8), fukinone (9), petasitolone (10), beta-eudesmol (11), trans-3beta-(1
      hydroxy-1-methylethyl)- 8abeta-methyl-5-methylenedecalin-2-one (12), 10
      hydroxyaristolan-9-one (13), aristol-8-en-1-one (14), aristolan-9-en-1-one (15),
      and aristolan-1, 9-diene (16). This is the first study on the chemical
      consituents of A. hongkongensis, and all compounds were isolated from the genus
      Artabotrys for the first time.

PMID- 29171235
TI  - [Research on anticancer activity of isocorydine and its derivatives].
AB  - Isocorydine and its analogs were extracted from Dicranostigma leptopodum and
      Stephania yunnanensis through the method of natural products chemistry. Its
      derivatives were prepared by chemical structure modifications from isocorydine.
      MTT method was used to study the inhibitory effect of those compounds on the
      growth of HepG2, HeLa and MGC-803 cancer cell lines in vitro. The results showed
      that isocorydine and its analogs all have the growth inhibition for those cancer
      cell lines. This paper investigated the structure-activity relationship of
      isocorydine and its derivatives with anticancer activity in the aspect of
      stereochemical structure, functional groups positions of the compounds and the
      electron density of aromatic rings based on the single crystal diffraction
      structure and the molecular docking of EGFR and isocorydine.

PMID- 29171236
TI  - [Analysis and evaluation of chemically induced artificial agarwood].
AB  - In this study,the content of ethanol extraction of agarwood were performed
      following the method of Chinese Pharmacopoeia(ChP 2015 edition). The
      chromatographic fingerprints were established by GC-MS. Similarity Evaluation
      System for Chromatographic Fingerprint of traditional Chinese
      medicine(TCM)(version 2012) was employed to calculate the similarity of each
      chromatogram of agarwood. The ratios of sum peak area in the range of 170-270 min
      and 0-100 min of individual chromatogram were calculated using square peaks to
      normalization. AMDIS and RI were employed to identify the common and different
      peaks. Correlation coefficient P(corr) combined with Variable important in
      projection(VIP) value was employed to screen the different representative
      components based on OPLS-DA analysis. Grey related degree and TOPSIS were used to
      evaluate the quality of artificial agarwoods. The results showed that more than
      10.0% of the ethanol extract content was found in 15 batches of artificial
      agarwoods among the total 18. The similarity of 18 batches artificial agarwoods
      was 0.439-0.779. The peak area ratios of two intervals were in the range of 0.307
      13.254. The 9 common components and 8 different components were identified.
      Meanwhile, 2% salicylic acid is the best inducer based on grey related degree and
      TOPSIS. Grey related degree and TOPSIS can be used to evaluate the quality of
      artificial agarwoods rapidly. These results provide a reference data to evaluate
      the qualityof artificial agarwood.

PMID- 29171237
TI  - [Analysis of influencing factors of secondary metabolites contents in cultivated
      Polygala tenuifolia].
AB  - This work was launched to explore the effect of habitat and growth year on the
      secondary metabolites contents of cultivated Polygala tenuifolia. The samples of
      cultivated P. tenuifolia were analyzed by ultra-high performance liquid
      chromatography(UPLC)-quadrupole time-of-flight mass spectrometry(Q-TOF MS), and
      the obtained data were analyzed using multiple statistical analysis and cluster
      analysis. The results showed that compared with growth year, habitat is a main
      influencing factor which affected the secondary metabolites contents of P.
      tenuifolia. The contents of sucrose esters and oligosacchride multi-esters are
      greatly dependent on the habitat (the sample-AG with high levels of components of
      tenuifoliside B and tenuifoliside C, and the sample-FY with high levels of 3,6'
      disinapoyl sucrose, tenuifoliose S, tenuifoliose L, and tenuifoliose V). There is
      no obvious effect of habitat and growth year on xanthone. The contents of
      triterpene saponins are greatly dependent on the growth year, and the content of
      parts of triterpene saponins increased as time goes on.The result indicated that
      the effect of habitat and growth year on different types of secondary metabolites
      is not completely equivalent. This study will contribute to the breeding of P.
      tenuifolia and amendment of current commodity criteria.

PMID- 29171238
TI  - [Investigation on stability and degradation kinetics of febrifugine].
AB  - To investigate the stability and degradation kinetics of febrifugine. The results
      showed that within 24 hours, febrifugine content was decreased by only 1% in
      mobile phase solvent, but its content was decreased to be 90% of the initial
      content in the water, methanol, 50% methanol and 10% acetonitrile solution. When
      the pH value of the solution was between 3 and 7, the retention rate of
      febrifugine in 24 hours was over 98%, but its content was decreased by about 12%
      in alkaline solution (pH 9.0). The higher the temperature, the worse the
      stability of febrifugine. At 40-80 C, the content of febrifugine was decreased to
      be 60% of its initial content in 10 hours, but the content was decreased by only
      5% in 10 h at 20 C.However, no matter 40 Cor 60 C, febrifugine was mainly
      transformed into isofebrifugine, and the total content of febrifugine and
      isofebrifugine was equal to their initial total content in 10 hours, while incase
      of 80 C, the total content was decreased to be 83.33% in 10 h, which suggested
      that the structure of febrifugine was absolutely changed, not just isomerized to
      be isofebrigugine at high temperature. Light had a significant impact on the
      stability of febrifugine. Under bright light, the content of febrifugine was
      reduced by about 23% in 108 h, but it only decreased by about 10% in the natural
      light or darkness. In artificial gastric fluid (pH 1.4) and artificial intestinal
      fluid (pH 6.8), the content of febrifugine was decreased by less than 5% in 10 h.
      After storage at high temperature(60 C), high humidity [(75+/-1)%] and strong
      light (3 000 lx) conditions for 10 d, the content of solid febrifugine was
      decreased by 0.27%, 7.6% and 5.39%, respectively. The degradation of febrifugine
      basically complied with the first-order reaction kinetic process in the following
      conditions: in water, methanol, 50%methanol and 10% acetonitrile solvents,
      alkaline solution (pH>7), different light intensity and different temperatures
      (20,40 C). Therefore, no matter the isolation and purification of febrifugine or
      the production of the related preparations, it should be done fast in the acidic
      solution, low temperature and dark conditions, while the febrifugine solid should
      be kept in dry and dark conditions.

PMID- 29171239
TI  - [Butyl alcohol extract of Baitouweng decoction inhibits Candida albicans cell
      membrane].
AB  - To study the inhibitory effect of butyl alcohol extract of Baitouweng
      decoction(BAEB) on Candida albicans cell membrane. The effects of BAEB on the
      activity of C. albicans were observed by Spot assay. The changes of intracellular
      osmotic pressure of C. albicans after BAEB intervention were detected by
      microtiter plate reader. The effect of BAEB on cell membrane permeability of C.
      albicans were observed by fluorescence microscopy. The content of ergosterol in
      C. albicans cell membrane was detected by high performance liquid chromatography,
      and the expression of ergosterol biosynthesis related genes in cell membrane was
      detected by qRT-PCR. The results showed that the activity of C. albicans was
      significantly decreased in 256, 512 and 1 024 mg*L-1 BAEB group. The
      intracellular glycerol content of C. albicans was significantly increased in 512
      and 1 024 mg*L-1 BAEB group(P<0.05). The gene HOG1 associated with intracellular
      osmotic pressure of C. albicans was down-regulated by 9.1, 9.3 and 5.5 times,
      respectively. C. albicans with red fluorescent were increased significantly in
      512 and 1 024 mg*L-1 BAEB group. The peak area of ergosterol in the 1 024 mg*L-1
      BAEB group was 35.884 95, with a significant difference(P<0.05); ERG1, ERG2,
      ERG3, ERG4, ERG5, ERG6, ERG10, ERG11, ERG13, ERG24, ERG25, ERG251, ERG26 and UPC2
      were down-regulated by 6.58, 4.89, 4.15, 9.24,3.41, 9.84, 3.08, 7.50, 5.53, 5.90,
      2.45, 3.25,1.98 and 10.07 times respectively in 1 024 mg*L-1 BAEB group. The
      study indicated that BAEB could inhibit ergosterol and its biosynthesis related
      genes expression in the cell membrane and inhibit the activity of C. albicans.

PMID- 29171240
TI  - [Effect of leech on VSMCs in early atherosclerosis rats via p38MAPK signaling
      pathway].
AB  - To explore the effect of leech on proliferation and apoptosis of vascular smooth
      muscle cells(VSMCs) in early atherosclerosis rats via p38MAPK signaling pathway
      and investigate its possible mechanism. Biochemical analyzer was used to examine
      the regulation of leech on levels of triglycerides(TG), total cholesterol(TC),
      low-density lipoprotein(LDL-C), and high-density lipoprotein(HDL-C) in blood
      lipid of rats. The expression of transforming growth factor-beta 1(TGF-beta1) in
      serum was detected by ELISA. Immunological histological chemistry (IHC) was taken
      to measure the expression levels of proliferating cell nucleus antigen(PCNA) and
      cell apoptosis proteinase-3(Caspase-3), while the protein expression levels of
      MKK3, p38 and C-myc were detected by Western blot. In addition, hematoxylin and
      eosin(HE) staining was used to observe the morphological change of thoracic
      aortas. The results showed that leech decreased the levels of TC, LDL-C obviously
      and increased HDL-C, suppressed the expression levels of TGF-beta1 and PCNA, up
      regulated Caspase-3, down-regulated the expression levels of MKK3, p38, and C-myc
      protein. HE staining indicated that it could inhibit intimal thickening and
      reduce plaque formation. The above results indicated that leech may affect the
      protein expression of the p38MAPK signaling pathway to inhibit proliferation and
      promote the apoptosis of VSMCs via reducing blood lipid levels and suppressing
      TGF-beta1, aiming at inhibiting intimal thickening and reducing plaque formation,
      tand then slowing down the process of early atherosclerosis.

PMID- 29171241
TI  - [Adverse reaction and screening of sensitizing substance of Shuxuening
      injection].
AB  - In this study, by the means of the active systemic allergy test in guinea pigs,
      passive skin allergy test in rats and pseudoallergic test in mice, it was
      determined that the "allergic reaction" of Shuxuening injection(SXNI) may not be
      a true IgE-mediated allergic reactions, but mainly of pseudoallergic reaction.
      Further pseudoallergic test proved that the pseudoallergic reactions of SXNI had
      difference between batches and showed dose dependence, so it was recommended to
      establish SXNI pseudoallergic reaction detection method for timely detecting and
      controlling the product risk of each batch products. In addition, as the
      pseudoallergic reactions of SXNI were dose-dependent, the dose and concentration
      of SXNI should be strictly controlled in clinical use. Then the main
      pseudoallergenic reaction test was conducted for the main monomer components in
      SXNI and the different fractions of Ginkgo biloba extract in mice, and the
      results showed that the sensitizing substances may mainly exist in YXY-3
      fractions containing flavonol glycosides. By further chemically separating YXY-3,
      we got four chemical components. Among these four components, YXY-3-1 and YXY-3-2
      were testified as the main allergenic components in SXNI through pseudoallergic
      test in mice. To make sure the specific chemical constituent that is responsible
      for the pseudoallergic reaction, in-depth study in follow-up experiments should
      be needed.

PMID- 29171242
TI  - [Absorption and transport of isoflavonoid compounds from Tongmai formula across
      human intestinal epithelial (Caco-2) cells in vitro].
AB  - Tongmai formula (TMF) is a drug combination of three components including
      Puerariae Lobatae Radix [roots of Pueraria lobata], Salviae Miltiorrhizae Radix
      (roots of Salvia miltiorrhiza) and Chuanxiong Rhizoma (rhizomes of Ligusticum
      chuanxiong) in a weight ratio of 1?1?1. The absorption and transport of
      isoflavonoid compounds from Tongmai formula across human intestinal epithelial
      (Caco-2) cells in vitro were studied in this paper. The assay isoflavonoid
      compounds include daidzein, formononetin, 5-hydroxylononin, ononin, daidzin, 3'
      methoxypuerarin, genistin, puerarin, formononetin-8-C-beta-D-apiofuranosyl-(1->6)
      O-beta-D-glucopyranoside, formononetin-7-O-beta-D-apiofuranosyl-(1->6)-O-beta-D
      glucopyranoside, lanceolarin, kakkanin, daidzein-7,4'-di-O-beta-D
      glucopyranoside, mirificin, 3'-hydroxypuerarin, 3'-methoxydaidzin, formononetin-8
      C-beta-D-xylopyranosyl-(1->6)-O-beta-D-glucopyranoside, genistein-8-C-beta-D
      apiofuranosyl-(1->6)-O-beta-D-glucopyranoside, genistein-7-O-beta-D-apiofuranosyl
      (1->6)-O-beta-D-glucopyranoside (ambocin), 3'-hydroxymirificin, 6"-O-beta-D
      xylosylpuerarin, biochanin A-8-C-beta-D-apiofuranosyl-(1->6)-O-beta-D
      glucopyranoside, 3'-methoxydaidzein-7,4'-di-O-beta-D-glucopyranoside, daidzein-7
      O-beta-D-glucopyranosyl-(1->4)-O-beta-D-glucopyranoside, and daidzein-7-O-alpha-D
      glucopyranosyl-(1->4)-O-beta-D-glucopyranoside. By using human Caco-2 monolayer
      as an intestinal epithelial cell model in vitro, the permeability of above
      mentioned 25 isoflavonoids in TMF were studied from the apical (AP) side to
      basolateral (BL) side or from the BL side to AP side. The assay compounds were
      determined by reversed phased high-performance liquid chromatography (HPLC)
      coupled with UV detector. Transport parameters and apparent permeability
      coefficients (Papp) were then calculated and and compared with those of
      propranolol and atenolol, which are the transcellular transport marker and as a
      control substance for high and poor permeability, respectively. The Papp values
      of daidzein and formononetin were (2.55+/-0.03) *10-5,(3.06+/-0.01) *10-5 cm*s-1
      from AP side to BL side, respectively, and (2.62+/-0.00) *10-5, (2.65+/-0.11) *10
      5 cm*s-1 from BL side to AP side, respectively. Under the condition of this
      experiment, the Papp value was (2.66+/-0.32) *10-5 cm*s-1 for propranolol and
      (2.34+/-0.10) *10-7 cm*s-1 for atenolol. The Papp values of daidzein and
      formononetin were at a same magnitude with those of propranolol. And the Papp
      values of other 23 isoflavonoid compounds were at a same magnitude with those of
      atenolol. On the other hand, the rats of Papp AP->BL/Papp BL->AP of daidzein and
      formononetin on the influx transport were 0.97 and 1.15, respectively. It can be
      predicted that daidzein and formononetin can be absorbed across intestinal
      epithelial cells to go to the body circulation by the passive diffusion mechanism
      and they were assigned to the well-absorbed compounds. Other 23 isoflavonoid
      compounds were assigned to the poorly absorbed compounds. Because of the rats of
      Papp AP->BL/Papp BL->AP of 5-hydroxylononin, genistin, lanceolarin, kakkanin, and
      genistein-7-O-beta-D-apiofuranosyl-(1->6)-O-beta-D-glucopyranoside were 0.18,
      0.28, 0.45, 0.38, 0.49, they may have been involved in the efflux mechanism in
      Caco-2 cells monolayer model from the BL side to AP side direction.

PMID- 29171243
TI  - [Medication rules for prescriptions containing Pterocephali Herba based on data
      mining].
AB  - This study was aimed to discuss and analyze the medication rules for
      prescriptions containing Pterocephali Herba in Chinese Medical Encyclopedia -
      Tibetan Medicine, Tibetan Medicine Prescription Modern Research and Clinical
      Application, and Interpretation of Common Tibetan Medicines based on the
      collection of Pterocephali Herba and by using the "Traditional Chinese Medicine
      Inheritance Support system(V2.0.1)",with the use of association rules, apriori
      algorithm and other data mining methods. The frequency of single drug, the
      frequency of drug combination, the association rule and the combination of core
      drugs were analyzed. Through collection of the prescriptions, a total of 215
      prescriptions were included, involving a total of 376 herbs. Through the
      "frequency statistics", the prescriptions containing Pterocephali Herba were
      commonly used to treat cold fever, distemper virus and arthritis. The highest
      frequently (frequency>=15) used drugs were Corydalis Herba, Lagotidis Herba, and
      Gentianae Macrophyllae Radix, et al. The most frequently used drug combinations
      were "Pterocephali Herba, Corydalis Herba","Pterocephali Herba, Lagotidis Herba",
      and "Pterocephali Herba, Gentianae Macrophyllae Radix" et al. The prescriptions
      containing Pterocephali Herba were used to primarily treat disease for Tourette
      syndrome caused by the dampness heat toxin, fever, arthritis etc, such as
      pestilent toxicity, pneumonia and influenza, rheumatoid arthritis etc. The drugs
      in the prescriptions mostly had the effects of heat-clearing and detoxifying,
      anti-inflammatory, dispelling wind and dampness, often in compatible use with
      heat-clearing drugs. The drug use was concentrated and reflected the clear
      thought of prescription statutes.

PMID- 29171244
TI  - [Identification of origin plant of Uygur medicine mulberry based on DNA barcode].
AB  - To provide molecular evidence for medical material identification, we analyzed
      the nucleotide sequence of ITS2, psbA-trnH gene in Morus genus plants and
      commercial products which were obtained from different places in Xinjiang. The
      sequence of ITS2 and psbA-trnH in fifty-one samples were amplified and sequenced,
      MEGA 6.0 was used to analyze the intra- and interspecific K-2P distances,
      neighbor-joining (NJ) tree was used to constructing clustering tree. ITS2
      sequence analyzed results showed that there is no intra-specific variation among
      Morus alba, M. alba var. tatarica and M. nigra, but 13 variations sites were
      exist between M. alba and M. nigra and their inter-specific K-2P distances was
      0.04, which indicated that there had significant variation in them. We didn't
      find informative variation sites between Morus genus plants and commercial
      products, and we also found that M. nigra can be distinguished from other two
      species by NJ Tree. PsbA-trnH analysis results showed there was only one
      variation site between M. alba and M. nigra, but insertion or deletion variation
      were remarkable evidence among M. alba, M. alba var. tatarica and M. Nigra. Inter
      specific variation was accordance with intra-specific variation of commercial
      products. So ITS2 and psbA-trnH gene were important marker for M. alba, M. alba
      var. tatarica and M. nigra identification. This study provided important evidence
      for Uygur medicine identification and market supervision.

PMID- 29171245
TI  - [Origin of lifting and lowering theory and its herb pair study].
AB  - Lifting and lowering theory is one of the important basis for guiding clinical
      medication. Through the study of ancient books and literature, we learned that
      lifting and lowering theory was originated in Huangdi Neijing, practiced more in
      the Shanghan Zabing Lun, established in Yixue Qiyuan, and developed in Compendium
      of Materia Medica and now. However, lifting and lowering theory is now mostly
      stagnated in the theoretical stage, with few experimental research. In the
      clinical study, the guiding role of lifting and lowering theory to
      prescriptions?mainly includes opposite?role?of lift and lower medicine property,
      mutual promotion of lift and lower medicine property, main role of lift medicine
      property and main role of lower medicine property. Under the guidance of lifting
      and lowering theory, the herb pair compatibility include herb combination of lift
      medicine property, herb combination of lift and lower medicine property and herb
      combination of lower medicine property. Modern biological technology was used in
      this study to carry out experimental research on the lifting and lowering theory,
      revealing the scientific connotation of it, which will help to promote clinical
      rational drug use.

PMID- 29171246
TI  - [Strategy of constructing post-market integral evaluation system of traditional
      Chinese medicine injection].
AB  - As an important representative of modern Chinese medicine, traditional Chinese
      medicine (TCM) injzection has become an indispensable part of the Chinese
      medicine industry. However, its development is now restricted by the bottleneck
      of insufficient core competitiveness, low-level research and production, even
      injection quality and the safe use are not guaranteed. Thus, it is urgent to
      reevaluate post-marketing TCM injection generally and to make secondary
      development. Under current circumstances, taking major brands which have good
      clinical and market foundation, as well as research value, as the main subject of
      cultivation and evaluation is an important approach to innovative development of
      TCM injection industry. Unlike oral proprietary Chinese medicine, the
      cultivatation of major brands of TCM injection needs higher technical support,
      quality standards and more timely feedback. Therefore, a post-market integral
      evaluation system adaptive to TCM injection is required. This article discussed
      some key points on the construction of a post-market integral evaluation system
      of TCM injection in three levels: optimizing evaluation methods, building
      synergistic innovation platforms which combine the medical research institutions
      and pharmaceutical enterprises, and finally constructing the integral evaluation
      system. A "five to one" structure has been proposed to enhance TCM injection
      effectiveness, safety and adaptability on the whole, which are from the following
      aspects: mechanism research, clinical evidence validation, literature information
      mining, sustainable development of resources and industrialization operation.

PMID- 29171247
TI  - Care of patients undergoing weaning from mechanical ventilation in critical care.
AB  - There are several reasons why mechanical ventilation - the use of an artificial
      device to assist a patient to breathe - may be initiated, for example to enable
      general anaesthesia for patients undergoing surgery, and for those with a
      compromised airway or respiratory failure. It is important that critical care
      nurses have the skills and knowledge to care for patients who are undergoing
      weaning from mechanical ventilation. This is to ensure that patients are weaned
      safely and as soon as possible, to improve their outcomes and avoid an increase
      in patient mortality and morbidity through complications that can arise such as
      airway trauma and ventilator-associated pneumonia. Furthermore, there are
      resource and cost implications of patients not being weaned as soon as possible.

PMID- 29171248
TI  - Methods of contraception: the nurse's role in providing care and advice.
AB  - Most women require contraception during their reproductive years, and many
      methods are available. Women should have access to all of these methods and be
      encouraged to take an active role in decision-making about their choice of
      contraceptive, within medical eligibility constraints. Long-acting reversible
      contraceptives are more effective than user-dependent methods, such as condoms,
      and should be offered to all women during contraceptive consultations. In primary
      care settings, nurses often provide much basic contraception care and advice.
      Nurses should ensure that they work within the limits of their competence and are
      aware of how and where to refer women for specialist support, if required.

PMID- 29171249
TI  - Chronic venous disease treated with sulodexide: a survey among primary care
      physicians in Mexico.
AB  - BACKGROUND: Sulodexide is a glycosaminoglycan approved for the treatment of
      chronic venous disease (CVD). It has been available in Mexico since 2012. The aim
      of the study was to understand the clinical experience of primary care physicians
      in the treatment of CVD with sulodexide. METHODS: Clinical data collection forms
      were distributed among general practitioners. Data was collected for up to four
      follow-up consultations. All signs and symptoms were rated with the Likert Scale
      at each examination: 0 to 5 (where 0 means none, and 5 very severe). Both the
      patient's and the physician's opinions of the effects of the treatment were
      recorded. RESULTS: Data were collected from 1599 patients at different clinical
      stages of CVD, 52% of which were at advanced stages (C4-C6). A total of 434 cases
      were followed up with four examinations (median of thirty days between each
      examination). In these cases, the overall sign and symptom score decreased
      significantly at each examination (P<0.01). At the fourth examination, 98.9% of
      the patients felt better or much better than at the first examination, and 99.7%
      were better or much better in the physician's opinion (P<0.01). The only adverse
      effect was nausea, reported in two cases. CONCLUSIONS: Sulodexide was effective
      and well tolerated in the treatment of CVD.

PMID- 29171250
TI  - Progress towards poliomyelitis eradication: Pakistan, January 2016-September
      2017.

PMID- 29171251
TI  - Monolithically Integrated Si-on-AlN Mid-Infrared Photonic Chips for Real-Time and
      Label-Free Chemical Sensing.
AB  - Chip-scale chemical sensors were demonstrated using optical waveguides consisting
      of amorphous silicon (a-Si) and aluminum nitride (AlN). A mid-infrared (mid-IR)
      transparent AlN thin film was prepared by room-temperature sputtering, which
      exhibited high Al/N elemental homogeneity. The Si-on-AlN waveguides were
      fabricated by a complementary metal-oxide-semiconductor process. A sharp
      fundamental mode and low optical loss of 2.21 dB/cm were obtained. Label-free
      chemical identification and real-time monitoring were performed by scanning the
      mode spectrum while the waveguide was exposed to various chemicals. Continuous
      tracing of heptane and methanol was accomplished by measuring the waveguide
      intensity attenuation at lambda = 2.5-3.0 MUm, which included the characteristic 
      CH and -OH absorptions. The monolithically integrated Si-on-AlN waveguides
      established a new sensor platform that can operate over a broad mid-IR regime,
      thus enabling photonic chips for label-free chemical detection.

PMID- 29171252
TI  - Multichannel Dynamic Interfacial Printing: An Alternative Multicomponent Droplet
      Generation Technique for Lab in a Drop.
AB  - Generation of uniform emulsion droplets mixed with multiple components is one of
      the key issues in the field of lab in a drop. Traditionally, droplet microfluidic
      chips are often served as the prime choice while designing and fabricating
      microfluidic chips always rely on skilled technician and specialized equipment,
      severely restricting its wide accessibility. In this work, an alternative
      technique, called multichannel dynamic interfacial printing (MC-DIP), was
      proposed for multicomponent droplet generation. The MC-DIP device was designed
      modularly and could be set up manually without any microfabrication process,
      exhibiting full accessibility for freshmen after a brief training. This new
      technique owns advantages in the generation of droplets with predictable sizes
      and composites. Quantitative experiments of measuring minimum inhibitory
      concentration (MIC) value via mixing microbes and antibiotics into droplet were
      conducted to proving its application potential for lab in a drop. Further
      research on a clinical pathogenic strain revealed that this technique could be
      potentially applied in the clinical laboratory for antibiotic susceptibility
      testing.

PMID- 29171253
TI  - Can Carbamates Undergo Radical Oxidation in the Soil Environment? A Case Study on
      Carbaryl and Carbofuran.
AB  - Radical oxidation of carbamate insecticides, namely carbaryl and carbofuran, was
      investigated with spectroscopic (electron paramagnetic resonance [EPR] and UV
      vis) and theoretical (density functional theory [DFT] and ab initio orbital
      optimized spin-component scaled MP2 [OO-SCS-MP2]) methods. The two carbamates
      were subjected to reaction with *OH, persistent DPPH* and galvinoxyl radical, as
      well as indigenous radicals of humic acids. The influence of fulvic acids on
      carbamate oxidation was also tested. The results obtained with EPR and UV-vis
      spectroscopy indicate that carbamates can undergo direct reactions with various
      radical species, oxidizing themselves into radicals in the process. Hence, they
      are prone to participate in the prolongation step of the radical chain reactions
      occurring in the soil environment. Theoretical calculations revealed that from
      the thermodynamic point of view hydrogen atom transfer is the preferred mechanism
      in the reactions of the two carbamates with the radicals. The activity of
      carbofuran was determined experimentally (using pseudo-first-order kinetics) and
      theoretically to be noticeably higher in comparison with carbaryl and comparable
      with gallic acid. The findings of this study suggest that the radicals present in
      soil can play an important role in natural remediation mechanisms of carbamates.

PMID- 29171254
TI  - Near-Infrared-to-Ultraviolet Light-Mediated Photoelectrochemical Aptasensing
      Platform for Cancer Biomarker Based on Core-Shell NaYF4:Yb,Tm@TiO2 Upconversion
      Microrods.
AB  - Titanium dioxide (TiO2; as a potential photosensitizer) has good photocurrent
      performance and chemical stability but often exhibits low utilization efficiency
      under ultraviolet (UV) region excitation. Herein, we devised a near-infrared
      light-to-UV light-mediated photoelectrochemical (PEC) aptasensing platform for
      the sensitive detection of carcinoembryonic antigen (CEA) based on core-shell
      NaYF4:Yb,Tm@TiO2 upconversion microrods by coupling with target-triggered rolling
      circle amplification (RCA). The upconversion microrods synthesized through the
      hydrothermal reaction could act as a photosensing platform to convert the near
      infrared (near-IR) excitation into UV emission for generation of photoinduced
      electrons. The target analyte was determined on a functional magnetic bead by
      using the corresponding aptamers with a sandwich-type assay format. Upon target
      CEA introduction, a complex was first formed between capture aptamer-1-conjugated
      magnetic bead (Apt1-MB) and aptamer-2-primer DNA (Apt2-pDNA). Thereafter, the
      carried primer DNA by the aptamer-2 paired with linear padlock DNA to trigger the
      RCA reaction. The guanine (G)-rich product by RCA reaction was cleaved by
      exonuclease I and exonuclease III (Exos I/III), thereby resulting in the
      formation of numerous individual guanine bases to enhance the photocurrent of
      core-shell NaYF4:Yb,Tm@TiO2 upconversion microrods under near-IR illumination
      (980 nm). Under optimal conditions, the near-IR light-mediated PEC aptasensing
      system could exhibit good photoelectrochemical response toward target CEA and
      allowed for the detection of target CEA as low as 3.6 pg mL-1. High
      reproducibility and good accuracy were achieved for analysis of human serum
      specimens. Importantly, the near-IR-activated PEC aptasensing scheme provides a
      promising platform for ultrasensitive detection of other biomolecules.

PMID- 29171255
TI  - Voltage Control of Two-Magnon Scattering and Induced Anomalous Magnetoelectric
      Coupling in Ni-Zn Ferrite.
AB  - Controlling spin dynamics through modulation of spin interactions in a fast,
      compact, and energy-efficient way is compelling for its abundant physical
      phenomena and great application potential in next-generation voltage controllable
      spintronic devices. In this work, we report electric field manipulation of spin
      dynamics-the two-magnon scattering (TMS) effect in Ni0.5Zn0.5Fe2O4
      (NZFO)/Pb(Mg2/3Nb1/3)-PbTiO3 (PMN-PT) multiferroic heterostructures, which breaks
      the bottleneck of magnetostatic interaction-based magnetoelectric (ME) coupling
      in multiferroics. An alternative approach allowing spin-wave damping to be
      controlled by external electric field accompanied by a significant enhancement of
      the ME effect has been demonstrated. A two-way modulation of the TMS effect with
      a large magnetic anisotropy change up to 688 Oe has been obtained, referring to a
      24 times ME effect enhancement at the TMS critical angle at room temperature.
      Furthermore, the anisotropic spin-freezing behaviors of NZFO were first
      determined via identifying the spatial magnetic anisotropy fluctuations. A large
      spin-freezing temperature change of 160 K induced by the external electric field
      was precisely determined by electron spin resonance.

PMID- 29171256
TI  - Combination of Redox Assembly and Biomimetic Mineralization To Prepare Graphene
      Based Composite Cellular Foams for Versatile Catalysis.
AB  - Graphene-based materials with hierarchical structures and multifunctionality have
      gained much interest in a variety of applications. Herein, we report a facile,
      yet universal approach to prepare graphene-based composite cellular foams (GCCFs)
      through combination of redox assembly and biomimetic mineralization enabled by
      cationic polymers. Specifically, cationic polymers (e.g., polyethyleneimine,
      lysozyme, etc.) could not only reduce and simultaneously assemble graphene oxide
      (GO) into cellular foams but also confer the cellular foams with mineralization
      inducing capability, enabling the formation of inorganic nanoparticles (e.g.,
      silica, titania, silver, etc.). The GCCFs show highly porous structure and
      appropriate structural stability, where nanoparticles are well distributed on the
      surface of the reduced GO. Through altering polymer/inorganic pairs, a series of
      GCCFs are synthesized, which exhibit much enhanced catalytic performance in
      enzyme catalysis, heterogeneous chemical catalysis, and photocatalysis compared
      to nanoparticulate catalysts.

PMID- 29171257
TI  - Stereoselective Synthesis of Bicyclo[6.1.0]nonene Precursors of the Bioorthogonal
      Reagents s-TCO and BCN.
AB  - The cyclooctyne BCN and the trans-cyclooctene s-TCO are widely used in
      bioorthogonal chemistry. A bottleneck for their synthesis had been a poorly
      selective cyclopropanation with ethyl diazoacetate. Here, we describe that low
      catalyst loadings (0.27 mol %) of Rh2( S-BHTL)4 provide the BCN precursor with
      79:21 syn/ anti selectivity. The synthesis of the s-TCO precursor was best
      achieved through a sequence of Rh2(OAc)4 (0.33 mol %)-catalyzed cyclopropanation,
      followed by ester hydrolysis under epimerizing conditions. Both sequences could
      be carried out on multigram scale.

PMID- 29171258
TI  - Construction of Plasmonic Ag and Nitrogen-Doped Graphene Quantum Dots Codecorated
      Ultrathin Graphitic Carbon Nitride Nanosheet Composites with Enhanced
      Photocatalytic Activity: Full-Spectrum Response Ability and Mechanism Insight.
AB  - The full utilization of solar energy has attracted great attention in the
      photocatalysis and environmental pollutant control. In this study, the local
      surface plasmon resonance effect of Ag nanoparticles (Ag NPs) with the
      upconversion property of nitrogen-doped graphene quantum dots (N-GQDs) was first
      combined for the formation of ternary Ag/N-GQDs/g-C3N4 nanocomposites. The
      prepared material presents enhanced full-spectrum light response ability, even in
      near-infrared (NIR) light. The experiment results disclosed that the 0.5% N-GQDs
      and 2.0% Ag NPs co-doped g-C3N4 show the highest photocatalytic activity,
      achieving 92.8 and 31.3% removal efficiency under full-spectrum light and NIR
      light irradiation, respectively, which was three-fold than that of pristine g
      C3N4. The boosted photocatalytic activity can be attributed to the synergistic
      effect among the g-C3N4, N-GQDs, and Ag NPs. The g-C3N4 nanosheets can serve as
      the reaction matrix and support for the dispersion of N-GQDs and Ag NPs,
      inhibiting their agglomeration. The existence of Ag NPs and N-GQDs can promote
      the light absorption and transfer ability, leading to the generation of more
      photoinduced charges. Simultaneously, N-GQDs and Ag NPs can efficiently transfer
      and reserve electrons, which can accelerate the photoinduced electrons'
      migration, inhibiting the recombination. The comprehensive effect of the reasons
      mentioned above resulted in the unique photocatalytic activity of the prepared
      Ag/N-GQDs/g-C3N4 nanocomposites. This study provides a new strategy for the
      formation of highly efficient photocatalysts with broad-spectrum light response
      ability and the potential for realistic wastewater pollution control.

PMID- 29171259
TI  - Label-Free and Recalibrated Multilayer MoS2 Biosensor for Point-of-Care
      Diagnostics.
AB  - Molybdenum disulfide (MoS2) field-effect transistor (FET)-based biosensors have
      attracted significant attention as promising candidates for highly sensitive,
      label-free biomolecule detection devices. In this paper, toward practical
      applications of biosensors, we demonstrate reliable and quantitative detection of
      a prostate cancer biomarker using the MoS2 FET biosensor in a nonaqueous
      environment by reducing nonspecific molecular binding events and realizing
      uniform chemisorption of anti-PSA onto the MoS2 surface. A systematic and
      statistical study on the capability of the proposed device is presented, and the
      biological binding events are directly confirmed and characterized through
      intensive structural and electrical analysis. Our proposed biosensor can reliably
      detect various PSA concentrations with a limit of 100 fg/mL. Moreover, rigorous
      theoretical simulations provide a comprehensive understanding of the operating
      mechanism of the MoS2 FET biosensors, and further suggests the enhancement of the
      sensitivity through engineering device design parameters.

PMID- 29171260
TI  - Engineering the Photoresponse of InAs Nanowires.
AB  - We report on individual-InAs nanowire optoelectronic devices which can be
      tailored to exhibit either negative or positive photoconductivity (NPC or PPC).
      The NPC photoresponse time and magnitude is found to be highly tunable by varying
      the nanowire diameter under controlled growth conditions. Using hysteresis
      characterization, we decouple the observed photoexcitation-induced hot electron
      trapping from conventional electric field-induced trapping to gain a fundamental
      insight into the interface trap states responsible for NPC. Furthermore, we
      demonstrate surface passivation without chemical etching which both enhances the
      field-effect mobility of the nanowires by approximately an order of magnitude and
      effectively eliminates the hot carrier trapping found to be responsible for NPC,
      thus restoring an "intrinsic" positive photoresponse. This opens pathways toward
      engineering semiconductor nanowires for novel optical-memory and photodetector
      applications.

PMID- 29171261
TI  - Aggregation-Induced Enhanced Electrochemiluminescence from Organic Nanoparticles
      of Donor-Acceptor Based Coumarin Derivatives.
AB  - Organic nanoparticles (NPs) from donor-acceptor based coumarin derivatives, 6-[4
      (N,N-diphenylamino)phenyl]-3-ethoxycarbonyl coumarin (DPA-CM), with an average
      size of 5.82 nm, were synthesized by a facile reprecipitation method using water
      as a poor solvent and tetrahydrofuran as a good solvent. Red-shifted absorption,
      blue-shifted photoluminescence emission, and aggregation-induced enhanced
      electrochemiluminescence (ECL) emission were observed for the DPA-CM NPs in
      aqueous solution compared with the original DPA-CM in organic solution. The
      aggregation-induced enhanced ECL emission is ascribed to the combined effects of
      the small size of the DPA-CM NPs, the restricted conformational relaxation in the
      NPs, and the good stability of the cationic radical of DPA-CM. A strong and
      stable ECL emission is obtained at the DPA-CM NPs modified glassy carbon
      electrode in the presence of tri-n-propylamine, and the ECL intensity of the DPA
      CM NPs modified electrode is quenched linearly in the range of 0.05-50 MUM with
      detection limit of 0.04, 0.2, and 0.4 MUM for ascorbic acid, uric acid, and
      dopamine, respectively. This work shows an example of donor-acceptor based
      organic NPs as ECL emitters and their analytical applications to monitor
      biomolecules.

PMID- 29171262
TI  - High-Yield and Sustainable Production of Phosphatidylserine in Purely Aqueous
      Solutions via Adsorption of Phosphatidylcholine on Triton-X-100-Modified Silica.
AB  - Triton X-100 was covalently bound to a surface of silica and acted as an anchor
      molecule to facilitate the adsorption of phosphatidylcholine (PC) in a purely
      aqueous solution. The silica-adsorbed PC obtained was successfully used for
      phospholipase D (PLD)-mediated transphosphatidylation in the production of
      phosphatidylserine (PS). Organic solvents were completely avoided in the whole
      production process. The PC loading and PS yield reached 98.9 and 99.0%,
      respectively. Two adsorption models were studied, and the relevant parameters
      were calculated to help us understand the adsorption and reaction processes
      deeply. In addition, the silica-adsorbed PC provides a promising way to
      continuously biosynthesize PS. A packed-bed reactor was employed to demonstrate
      the process flow of the continuous production of PS. The recyclability and
      stability of the Triton-X-100-modified silica were excellent, as demonstrated by
      its use 30 times during continuous operation without any loss of the
      productivity.

PMID- 29171263
TI  - A Small Molecule Nanodrug by Self-Assembly of Dual Anticancer Drugs and
      Photosensitizer for Synergistic near-Infrared Cancer Theranostics.
AB  - Phototherapy including photodynamic therapy (PDT) and photothermal therapy (PTT)
      has attracted great attention. However, applications of some photosensitizers
      remain an obstacle by their poor photostability. To enhance the treatment
      efficiency of photosensitizers and tumor theranostic effect, herein, we reported
      a novel carrier-free, theranostic nanodrug by self-assembly of small molecule
      dual anticancer drugs and photosensitizer for tumor targeting. The developed
      carrier-free small molecule nanodrug delivery system was formed by hydrophobic
      ursolic acid, paclitaxel, and amphipathic indocyanine green (ICG) associated with
      electrostatic, pi-pi stacking, and hydrophobic interactions exhibiting water
      stability. The self-assembling of ICG on the dual anticancer nanodrug
      significantly enhanced water solubility of hydrophobic anticancer drugs and ICG
      photostability contributing to long-term near-infrared (NIR) fluorescence imaging
      and effective chemophototherapy of tumor. The in vivo NIR fluorescence imaging
      showed that the theranostic nanodrug could be targeted to the tumor site via a
      potential enhanced permeability and retention effect proving the efficient
      accumulation of nanoparticles in the tumor site. Dramatically, chemophototherapy
      of tumor-bearing mice in vivo almost completely suppressed tumor growth and no
      tumor recurrence was observed. Encouraged by its carrier-free, prominent imaging
      and effective therapy, the small molecule nanodrug via self-assembly will provide
      a promising strategy for synergistic cancer theranostics.

PMID- 29171264
TI  - Radiopaque Resists for Two-Photon Lithography To Enable Submicron 3D Imaging of
      Polymer Parts via X-ray Computed Tomography.
AB  - Two-photon lithography (TPL) is a high-resolution additive manufacturing (AM)
      technique capable of producing arbitrarily complex three-dimensional (3D)
      microstructures with features 2-3 orders of magnitude finer than human hair. This
      process finds numerous applications as a direct route toward the fabrication of
      novel optical and mechanical metamaterials, miniaturized optics, microfluidics,
      biological scaffolds, and various other intricate 3D parts. As TPL matures,
      metrology and inspection become a crucial step in the manufacturing process to
      ensure that the geometric form of the end product meets design specifications. X
      ray-based computed tomography (CT) is a nondestructive technique that can provide
      this inspection capability for the evaluation of complex internal 3D structure.
      However, polymeric photoresists commonly used for TPL, as well as other forms of
      stereolithography, poorly attenuate X-rays due to the low atomic number (Z) of
      their constituent elements and therefore appear relatively transparent during
      imaging. Here, we present the development of optically clear yet radiopaque
      photoresists for enhanced contrast under X-ray CT. We have synthesized iodinated
      acrylate monomers to formulate high-Z photoresist materials that are capable of
      forming 3D microstructures with sub-150 nm features. In addition, we have
      developed a formulation protocol to match the refractive index of the
      photoresists to the immersion medium of the objective lens so as to enable dip-in
      laser lithography, a direct laser writing technique for producing millimeter-tall
      structures. Our radiopaque photopolymer resists increase X-ray attenuation by a
      factor of more than 10 times without sacrificing the sub-150 nm feature
      resolution or the millimeter-scale part height. Thus, our resists can
      successfully replace existing photopolymers to generate AM parts that are
      suitable for inspection via X-ray CT. By providing the "feedstock" for radiopaque
      AM parts, our resist formulation is expected to play a critical role in enabling
      fabrication of functional polymer parts to tight design tolerances.

PMID- 29171265
TI  - Surface-Mediated Energy Transfer and Subsequent Photocatalytic Behavior in
      Silicon Carbide Colloid Solutions.
AB  - We demonstrate that particle-particle interaction affects the photocatalytic
      efficiency of colloids. Colloid silicon carbide nanoparticles were examined by
      varying their size, size distribution, and surface chemistry, and we found that
      surface moieties show no effect on the individual particles but dramatically
      affect the collective photocatalytic efficiency of the system.

PMID- 29171266
TI  - Toward a Unified Total Synthesis of the Xiamycin and Oridamycin Families of
      Indolosesquiterpenes.
AB  - A unified synthetic strategy toward the oridamycin and xiamycin families of
      natural products was designed, aiming to access several natural products from a
      common synthetic intermediate readily prepared from geranyl acetate. Part of this
      strategy was successfully realized, culminating in the synthesis of oridamycin A
      and oridamycin B. Key steps include a Mn(III)-mediated oxidative radical
      cyclization to construct the trans-decalin ring, and a 6pi
      electrocyclization/aromatization sequence to produce the 2,3-fused carbazole.
      Oridamycin B was accessed through a late-stage, C-H oxidation that converted the
      C16 methyl to a hydroxymethyl. A variety of strategies were explored to form a
      chelated radical intermediate en route to xiamycin A, including enolate SET
      oxidation, oxo-vanadium oxidation, and atom-transfer cyclization. Unfortunately,
      none of these strategies provided the desired C16-epimeric trans-decalin.
      Exploratory studies on photoredox-catalyzed radical cyclizations yielded
      interesting results, including the formation of a bicyclic lactone arising from
      oxidative termination of the photoredox-catalyzed radical cyclization, and a
      double 6-endo cyclization with catalyst loadings as low as 0.01 mol%.

PMID- 29171267
TI  - UHPLC-Q-TOF-MS/MS Method Based on Four-Step Strategy for Metabolism Study of
      Fisetin in Vitro and in Vivo.
AB  - Fisetin has been identified as an anticancer agent with antiangiogenic properties
      in mice. However, its metabolism in vitro (rat liver microsomes) and in vivo
      (rats) is presently not characterized. In this study, ultra-high-performance
      liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass
      spectrometry (UHPLC-Q-TOF-MS) was employed for data acquiring, and a four-step
      analytical strategy was developed to screen and identify metabolites. First, full
      scan was applied, which was dependent on a multiple mass defect filter (MMDF)
      combined with dynamic background subtraction (DBS). Then PeakView 1.2 and
      Metabolitepilot 1.5 software were used to load data to seek possible metabolites.
      Finally, metabolites were identified according to mass measurement and retention
      time. Moreover, isomers were distinguished based on Clog P parameter. Based on
      the proposed method, 53 metabolites in vivo and 14 metabolites in vitro were
      characterized. Moreover, metabolic pathways mainly included oxidation, reduction,
      hydrogenation, methylation, sulfation, and glucuronidation.

PMID- 29171268
TI  - Quantification of Gold Nanoparticle Ultraviolet-Visible Extinction, Absorption,
      and Scattering Cross-Section Spectra and Scattering Depolarization Spectra: The
      Effects of Nanoparticle Geometry, Solvent Composition, Ligand Functionalization,
      and Nanoparticle Aggregation.
AB  - Using the recent polarized resonance synchronous spectroscopic (PRS2) technique,
      we reported the quantification of photon extinction, absorption, scattering cross
      section spectra, and scattering depolarization spectra for AuNPs of different
      sizes and shapes. The effects of the solvent composition, ligand
      functionalization, and nanoparticle aggregation on the AuNP photon absorption and
      scattering have also been experimentally quantified. The light scattering
      depolarization is close to 0 for gold nanospheres (AuNSs) crossing the entire UV
      vis region but is strongly wavelength-dependent for gold nanorods (AuNRs).
      Increasing the dielectric constant of the medium surrounding AuNPs either by
      solvents or ligand adsorption increases photon absorption and scattering but has
      no significant impact on the AuNP scattering depolarization. Nanoparticle
      aggregation increases AuNP photon scattering. However, even the extensively
      aggregated AuNPs remain predominantly photon absorbers with photon scattering-to
      extinction ratios all less than 0.03 for the investigated AuNP aggregates at the
      AuNP peak extinction wavelength. The AuNP scattering depolarization initially
      increases with the AuNP aggregation but decreases when aggregation further
      progresses. The insights from this study are important for a wide range of AuNP
      applications that involve photon/matter interactions, while the provided
      methodology is directly applicable for experimental quantification of optical
      properties for nanomaterials that are commonly simultaneously photon absorbers
      and scatterers.

PMID- 29171269
TI  - Synthesis of Dicyanovinyl-Substituted 1-(2-Pyridyl)pyrazoles: Design of a
      Fluorescent Chemosensor for Selective Recognition of Cyanide.
AB  - A fluorescence "turn-off" probe has been designed and successfully applied to
      detect cyanide (CN-) based on a Michael-type nucleophilic addition reaction and
      intramolecular charge transfer (ICT) mechanism. For this research, a family of 3
      aryl-4-(2,2-dicyanovinyl)-1-(2-pyridinyl)pyrazoles as donor-pi-acceptor (D-pi-A)
      systems have been synthesized in 58-66% overall yield, by a three-step synthesis
      sequence starting from p-substituted acetophenones. The substituted p
      methoxyphenyl showed good fluorescence emission and large Stokes shifts in
      different solvents due to its greater ICT. Likewise, this probe evidenced high
      selectivity and sensitivity and fast recognition for CN- with a detection limit
      of 6.8 MUM. HRMS analysis, 1H NMR titration experiments, and TD-DFT calculations
      were performed to confirm the mechanism of detection and fluorescence properties
      of the chemodosimeter of CN-. Additionally, fluorescent test paper was
      conveniently used to detect cyanide in aqueous solution.

PMID- 29171270
TI  - Genetically Encoded Chemical Decaging in Living Bacteria.
AB  - We report the genetically encoded chemical decaging strategy for protein
      activation in living bacterial cells. In contrast to the metabolically labile
      photocaging groups inside Escherichia coli, our chemical decaging strategy that
      relies on the inverse electron-demand Diels-Alder (iDA) reaction is compatible
      with the intracellular environment of bacteria, which can be a general tool for
      gain-of-function study of a given protein in prokaryotic systems. By applying
      this strategy for in situ activation of the indole-producing enzyme TnaA, we
      built an orthogonal and chemically inducible indole production pathway inside E.
      coli cells, which revealed the role of indole in bacterial antibiotic tolerance.

PMID- 29171271
TI  - Biosynthetic Pathway and Metabolic Engineering of Plant Dihydrochalcones.
AB  - Dihydrochalcones are plant natural products containing the phenylpropanoid
      backbone and derived from the plant-specific phenylpropanoid pathway.
      Dihydrochalcone compounds are important in plant growth and response to stresses
      and, thus, can have large impacts on agricultural activity. In recent years,
      these compounds have also received increased attention from the biomedical
      community for their potential as anticancer treatments and other benefits for
      human health. However, they are typically produced at relatively low levels in
      plants. Therefore, an attractive alternative is to express the plant biosynthetic
      pathway genes in microbial hosts and to engineer the metabolic pathway/host to
      improve the production of these metabolites. In the present review, we discuss in
      detail the functions of genes and enzymes involved in the biosynthetic pathway of
      the dihydrochalcones and the recent strategies and achievements used in the
      reconstruction of multi-enzyme pathways in microorganisms in efforts to be able
      to attain higher amounts of desired dihydrochalcones.

PMID- 29171272
TI  - A C-H Oxidation/Two-Fold Cyclization Approach to Imidazopyridoindole Scaffold
      under Mild Oxidizing Conditions.
AB  - An expeditious one-step synthesis of the imidazopyridoindole scaffold was
      achieved through the C-H oxidation/two-fold cyclization reaction of methyl ketone
      and tryptamine derivatives. Mild oxidizing conditions were employed to realize
      the efficient oxidation of C(sp3)-H bonds, while suppressing overoxidation of the
      intermediate and ensuring the cross-trapping of two in situ generated acylimine
      intermediates.

PMID- 29171273
TI  - Surface Mechanoengineering of a Zr-Based Bulk Metallic Glass via Ar-Nanobubble
      Doping To Probe Cell Sensitivity to Rigid Materials.
AB  - In this study, a new materials platform, utilizing the amorphous microstructure
      of bulk metallic glasses (BMGs) and the versatility of ion implantation, was
      developed for the fundamental investigation of cell responses to substrate
      rigidity variations in the gigapascal modulus range, which was previously
      unattainable with polymeric materials. The surface rigidity of a Zr-Al-Ni-Cu-Y
      BMG was modulated with low-energy Ar-ion implantation because of the impartment
      of Ar nanobubbles into the amorphous matrix. Surface softening was achieved due
      to the formation of nanobubble-doped transitional zones in the Zr-based BMG
      substrate. Bone-forming cell studies on this newly designed platform demonstrated
      that mechanical cues, accompanied by the potential effects of other surface
      properties (i.e., roughness, morphology, and chemistry), contributed to
      modulating cell behaviors. Cell adhesion and actin filaments were found to be
      less established on less stiff surfaces, especially on the surface with an
      elastic modulus of 51 GPa. Cell growth appeared to be affected by surface
      mechanical properties. A lower stiffness was generally related to a higher growth
      rate. Findings in this study broadened our fundamental understanding concerning
      the mechanosensing of bone cells on stiff substrates. It also suggests that
      surface mechanoengineering of metallic materials could be a potential strategy to
      promote osseointegration of such materials for bone-implant applications. Further
      investigations are proposed to fine-tune the ion implantation variables in order
      to further distinguish the surface-mechanical effect on bone-forming cell
      activities from the contributions of other surface properties.

PMID- 29171275
TI  - Single-Use Poly(etheretherketone) Solid-Phase Microextraction-Transmission Mode
      Devices for Rapid Screening and Quantitation of Drugs of Abuse in Oral Fluid and
      Urine via Direct Analysis in Real-Time Tandem Mass Spectrometry.
AB  - The analysis of oral fluid (OF) and urine samples to detect drug consumption has
      garnered considerable attention as alternative biomatrices. Efficient
      implementation of microextraction and ambient ionization technologies for rapid
      detection of target compounds in such biomatrices creates a need for
      biocompatible devices which can be implemented for in vivo sampling and easily
      interfaced with mass spectrometry (MS) analyzers. This study introduces a novel
      solid-phase microextraction-transmission mode (SPME-TM) device made of
      poly(etheretherketone) (PEEK) mesh that can rapidly detect prohibited substances
      in biofluids via direct analysis in real-time tandem MS (DART-MS/MS). PEEK mesh
      was selected due to its biocompatibility, excellent resistance to various organic
      solvents, and its ability to withstand relatively high temperatures (<=350 
      degrees C). The meshes were coated with hydrophilic-lipophilic-balance particle
      poly(acrylonitrile) (HLB-PAN) slurry. The robustness of the coated meshes was
      tested by performing rapid vortex agitation (>=3200 rpm) in LC/MS-grade solvents
      and by exposing them to the DART source jet stream at typical operational
      temperatures (~250-350  degrees C). PEEK SPME-TM devices proved to be robust and
      were therefore used to perform ex vivo analysis of drugs of abuse spiked in urine
      and OF samples. Excellent results were obtained for all analytes under study;
      furthermore, the tests yielded satisfactory limits of quantitation (median, ~0.5
      ng mL-1), linearity (>=0.99), and accuracy (80-120%) over the evaluated range
      (0.5-200 ng mL-1). This research highlights plastic SPME-TM's potential
      usefulness as a method for rapidly screening for prohibited substances in on
      site/in vivo scenarios, such as roadside or workplace drug testing, antidoping
      controls, and pain management programs.

PMID- 29171274
TI  - Spontaneous Lipid Nanodisc Fomation by Amphiphilic Polymethacrylate Copolymers.
AB  - There is a growing interest in the use of lipid bilayer nanodiscs for various
      biochemical and biomedical applications. Among the different types of nanodiscs,
      the unique features of synthetic polymer-based nanodiscs have attracted
      additional interest. A styrene-maleic acid (SMA) copolymer demonstrated to form
      lipid nanodiscs has been used for structural biology related studies on membrane
      proteins. However, the application of SMA polymer based lipid nanodiscs is
      limited because of the strong absorption of the aromatic group interfering with
      various experimental measurements. Thus, there is considerable interest in the
      development of other molecular frameworks for the formation of polymer-based
      lipid nanodiscs. In this study, we report the first synthesis and
      characterization of a library of polymethacrylate random copolymers as
      alternatives to SMA polymer. In addition, we experimentally demonstrate the
      ability of these polymers to form lipid bilayer nanodiscs through the
      fragmentation of lipid vesicles by means of light scattering, electron
      microscopy, differential scanning calorimetry, and solution and solid-state NMR
      experiments. We further demonstrate a unique application of the newly developed
      polymer for kinetics and structural characterization of the aggregation of human
      islet amyloid polypeptide (also known as amylin) within the lipid bilayer of the
      polymer nanodiscs using thioflavin-T-based fluorescence and circular dichroism
      experiments. Our results demonstrate that the reported new styrene-free polymers
      can be used in high-throughput biophysical experiments. Therefore, we expect that
      the new polymer nanodiscs will be valuable in the structural studies of amyloid
      proteins and membrane proteins by various biophysical techniques.

PMID- 29171276
TI  - Pericardial effusion following cardiac surgery. A single-center experience.
AB  - Background Pericardial effusion is still a common postoperative complication
      after open heart surgery with cardiopulmonary bypass. Pericardial effusion
      significantly prolongs the hospital stay and associated costs as well as
      affecting overall outcomes after open heart surgery in Hanoi Heart Hospital, a
      tertiary hospital in Vietnam with an annual volume of 1000 patients. This study
      aimed to investigate the clinical presentation, incidence, and risk factors of
      postoperative pericardial effusion, which may ensure better prevention of
      pericardial effusion and improvement in surgical outcomes after open heart
      surgery. Methods A cross-sectional study was performed on 1127 patients
      undergoing open heart surgery from January 2015 to December 2015. Results Thirty
      six (3.19%) patients developed pericardial effusion. Of these, 16 (44.4%) had
      cardiac tamponade. Pericardial effusion occurred after valve procedures in 77.8%
      of cases. Pericardial effusion was detected after discharge in 47.2% of cases at
      a mean time of 18.1 +/- 13.7 days. Univariate logistic regression analysis showed
      that age > 25 years, body surface area >= 1.28 m2, preoperative liver
      dysfunction, New York Heart Association class III/IV, left ventricular end
      diastolic diameter z score >= 0.55, and postoperative anticoagulant use were
      associated with postoperative pericardial effusion. Multivariate logistic
      regression analysis showed that left ventricular end-diastolic diameter z score
      >= 0.55 was an independent risk factor for postoperative pericardial effusion.
      Conclusions Routine postoperative echocardiography is necessary to detect
      postoperative pericardial effusion. Increased left ventricular end-diastolic
      dimension is an independent predictor of postoperative pericardial effusion.

PMID- 29171277
TI  - Corrigendum.
AB  - Corrigendum to: Carter G, Page A, Large M, et al. (2016) Royal Australian and New
      Zealand College of Psychiatrists clinical practice guideline for the management
      of deliberate self-harm. Australian and New Zealand Journal of Psychiatry 50: 939
      1000. Readers should note an error in the published version of this article: The
      previous list of authors and affiliations inadvertently omitted the details of Dr
      Michael Dudley. The correct author list and affiliation details appear below:
      Gregory Carter1,2,3, Andrew Page1,4, Matthew Large1,5, Sarah Hetrick1,6, Allison
      Joy Milner1,7,8, Nick Bendit1,9,10, Carla Walton1,11, Brian Draper1,12,13, Philip
      Hazell1,14, Sarah Fortune1,15,16,17, Jane Burns1,18,19,20, George
      Patton1,21,22,23,24, Mark Lawrence1,25, Lawrence Dadd1,26,27,28,29, Michael
      Dudley1, 12, Jo Robinson1,6, and Helen Christensen1,30 1 Clinical Practice
      Guideline for Deliberate Self-harm Working Group, RANZCP, Melbourne, Victoria,
      Australia 2 Centre for Translational Neuroscience and Mental Health, Faculty of
      Health and Medicine, The University of Newcastle, Callaghan, NSW, Australia 3
      Department of Consultation Liaison Psychiatry, Calvary Mater Newcastle Hospital,
      Waratah, NSW, Australia 4 Centre for Health Research, Western Sydney University,
      Richmond, NSW, Australia 5 School of Psychiatry, The University of New South
      Wales, Sydney, NSW, Australia 6 Orygen, The National Centre of Excellence in
      Youth Mental Health, Melbourne, VIC, Australia 7 Centre for Population Health
      Research, School of Health and Social Development, Deakin University, Burwood
      VIC, Australia 8 Melbourne School of Population and Global Health, The University
      of Melbourne, Melbourne, VIC, Australia 9 School of Medicine and Public Health,
      Faculty of Health and Medicine, The University of Newcastle, Callaghan, NSW,
      Australia 10 School of Psychology, Faculty of Science and Information Technology,
      The University of Newcastle, Callaghan, NSW, Australia 11 Centre for
      Psychotherapy, Hunter New England Mental Health Service and Centre for
      Translational Neuroscience and Mental Health, The University of Newcastle,
      Callaghan, NSW, Australia 12 School of Psychiatry, The University of New South
      Wales, Sydney, NSW, Australia 13 Academic Department for Old Age Psychiatry,
      Prince of Wales Hospital, Sydney, NSW, Australia 14 Discipline of Psychiatry,
      Sydney Medical School, The University of Sydney, Sydney, NSW, Australia 15 The
      University of Auckland, Auckland, New Zealand 16 University of Leeds, Leeds, UK
      17 Kidz First, Middlemore Hospital, Auckland, New Zealand 18 Young and Well
      Cooperative Research Centre, The University of Melbourne, Melbourne, VIC,
      Australia 19 Brain & Mind Research Institute, The University of Sydney, Sydney,
      NSW, Australia 20 Orygen Youth Health Research Centre, Melbourne, VIC, Australia
      21 Department of Paediatrics, The University of Melbourne, Melbourne, VIC,
      Australia 22 National Health and Medical Research Council, Canberra, ACT,
      Australia 23 Centre for Adolescent Health, The Royal Children's Hospital,
      Melbourne, VIC, Australia 24 Murdoch Children's Research Institute, Melbourne,
      VIC, Australia 25 Tauranga Hospital, Bay of Plenty, New Zealand 26 Mental Health
      & Substance Use Service, Hunter New England, NSW Health, Waratah, NSW, Australia
      27 Awabakal Aboriginal Medical Service, Hamilton, NSW, Australia 28 Pital Tarkin,
      Aboriginal Medical Student Mentoring Program, The Wollotuka Institute, The
      University of Newcastle, Callaghan, NSW, Australia 29 Specialist Outreach NT,
      Darwin, Northern Territory, Australia 30 Black Dog Institute, The University of
      New South Wales, Sydney, NSW, Australia The authors apologise for this oversight.

PMID- 29171278
TI  - Effects of Sociodemographic Characteristics and Personality Traits on Career
      Development.
AB  - The aim of this study was to identify which employees' sociodemographic
      characteristics and personality traits affected their career development. The
      research was conducted on a sample of 462 employees, aged between 30 and 55. The
      final analysis of covariance model included only characteristics which had
      previously been identified as having significant effect and relations with career
      development: gender, age, education level, years of work experience with the
      current employer, total years of work experience, financial status, and all Big
      Five traits. It was determined that the following characteristics had a
      significant effect on career development: gender, years of work experience with
      the current employer, and financial status, from the set of sociodemographic
      characteristics, as well as Conscientiousness, from the personality traits.
      Sociodemographic characteristics and personality traits, especially
      Conscientiousness, represent significant determinants in career development.

PMID- 29171279
TI  - Dietary Supplement Adverse Event Report Data From the FDA Center for Food Safety
      and Applied Nutrition Adverse Event Reporting System (CAERS), 2004-2013.
AB  - BACKGROUND: The Food and Drug Administration (FDA)'s Center for Food Safety and
      Applied Nutrition (CFSAN) oversees the safety of the nation's foods, dietary
      supplements, and cosmetic products. OBJECTIVE: To present a descriptive analysis
      of the 2004-2013 dietary supplement adverse event report (AER) data from CAERS
      and evaluate the 2006 Dietary Supplements and Nonprescription Drug Consumer
      Protection Act as pertaining to dietary supplements adverse events reporting.
      METHODS: We queried CAERS for data from the 2004-2013 AERs specifying at least 1
      suspected dietary supplement product. We extracted the product name(s), the
      symptom(s) reported, age, sex, and serious adverse event outcomes. We examined
      time trends for mandatory and voluntary reporting and performed analysis using
      SAS v9.4 and R v3.3.0 software. RESULTS: Of the total AERs (n = 15 430) received
      from January 1, 2004, through December 31, 2013, indicating at least 1 suspected
      dietary supplement product, 66.9% were mandatory, 32.2% were voluntary, and 0.9%
      were both mandatory and voluntary. Reported serious outcomes included death, life
      threatening conditions, hospitalizations, congenital anomalies/birth defects and
      events requiring interventions to prevent permanent impairments (5.1%). The
      dietary supplement adverse event reporting rate in the United States was
      estimated at ~2% based on CAERS data. CONCLUSIONS: This study characterizes CAERS
      dietary supplement adverse event data for the 2004-2013 period and estimates a
      reporting rate of 2% for dietary supplement adverse events based on CAERS data.
      The findings show that the 2006 Dietary Supplements and Nonprescription Drug
      Consumer Protection Act had a substantial impact on the reporting of adverse
      events.

PMID- 29171280
TI  - An analysis of integrated health care for Internet Use Disorders in adolescents
      and adults.
AB  - Background and aims Although first treatment approaches for Internet Use
      Disorders (IUDs) have proven to be effective, health care utilization remained
      low. New service models focus on integrated health care systems, which facilitate
      access and reduce burdens of health care utilization, and stepped-care
      interventions, which efficiently provide individualized therapy. Methods An
      integrated health care approach for IUD intended to (a) be easily accessible and
      comprehensive, (b) cover a variety of comorbid syndromes, and (c) take
      heterogeneous levels of impairment into account was investigated in a one-armed
      prospective intervention study on n = 81 patients, who were treated from 2012 to
      2016. Results First, patients showed significant improvement in Compulsive
      Internet Use over time, as measured by hierarchical linear modeling. Effect sizes
      of outcome change from baseline to 6-month follow-up ranged from d = 0.48 to d =
      1.46. Second, differential effects were found depending on patients' compliance,
      demonstrating that high compliance resulted in significantly higher rates of
      change. Third, patients referred to minimal interventions did not differ
      significantly in amount of change from patients referred to intensive
      psychotherapy. Discussion Tailored interventions result in higher efficiency
      through optimized resource allocation and equal amounts of symptom change in all
      treatment conditions. Moreover, comprehensive, low-threshold interventions seem
      to increase health service utilization.

PMID- 29171281
TI  - Complete Malleus Removal for Cholesteatoma: A Multivariate Analysis of
      Ossiculoplasty Success and Residual Disease.
AB  - OBJECTIVE: Determine the effect of complete malleus removal during canal wall up
      tympanomastoidectomy for cholesteatoma on ossiculoplasty success and rate of
      residual cholesteatoma. METHODS: We reviewed the operative, audiogram, and
      clinical reports of patients who underwent canal wall up tympanomastoidectomy for
      cholesteatoma between 2009 and 2016 at a tertiary academic medical center with at
      least 8 months of follow-up after surgery. To control for extent of disease, we
      independently catalogued the subsites of the middle ear and mastoid that
      cholesteatoma involved from each operation. We performed multivariate logistic
      regression to determine the independent effect of complete removal of the malleus
      on the rate of residual disease and success of ossiculoplasty. RESULTS: One
      hundred eighty surgeries were included in the analysis. For ossiculoplasty
      success, the adjusted odds ratio of complete malleus removal was 1.7 (95% CI,
      0.43-7.0, P = .43), which was not statistically significant. For residual
      disease, the adjusted odds ratio of complete malleus removal versus not was 0.29
      (95% CI, 0.074-1.1, P = .076), which approached but did not meet statistical
      significance. CONCLUSION: Though complete malleus removal does not independently
      decrease the rate of residual cholesteatoma, it may be a safe technique as it did
      not compromise ossiculoplasty success.

PMID- 29171282
TI  - (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one alleviates
      lipoteichoic acid-induced photoreceptor cell damage.
AB  - OBJECTIVE: Exposure to oxidative stress will lead to the progression of retinal
      degenerative diseases, and unfortunately the exact mechanisms have not been fully
      understood. In this study, the protective effects of (3R)-5,6,7-trihydroxy-3
      isopropyl-3-methylisochroman-1-one (TIM) against the lipoteichoic acid (LTA)
      induced cell damage in mouse photoreceptor-derived 661W cells were investigated.
      METHODS: 661W cells were pre-treated with TIM at different concentrations (0.1
      2.5 MUM) before exposure to LTA. The oxidative stress and inflammatory response
      were detected in 661W cells. RESULTS: Pre-treatment of 661W cells with TIM (0.1
      2.5 MUM) for 4 h significantly decreased the LTA-induced toxicity. Meanwhile, pre
      treatment with TIM could attenuate the imbalance state of redox in 661W cells by
      decreasing the levels of intracellular ROS and MDA, as well as enhancing the SOD
      activity and the level of GSH, through increasing the protein expression of Nrf2.
      Moreover, TIM pre-treatment decreased pro-inflammatory factors IL-1beta, IL-12
      and TNFalpha, through inhibiting the nuclear factor kappa B. Pre-treatment with
      TIM also suppressed Egr1, Fosl1, and Lox12 gene expression. CONCLUSION: These
      results suggested that TIM may exert its protective effects against LTA-induced
      toxicity in 661W cells, through counteracting the oxidative stress and inhibiting
      inflammatory response. Our findings provided the scientific rational to develop
      TIM in the treatment of oxidative stress-induced photoreceptor cell damage.

PMID- 29171283
TI  - Weightbearing Computed Tomography of the Foot and Ankle: Emerging Technology
      Topical Review.
AB  - : In the last decade, cone-beam computed tomography technology with improved
      designs allowing flexible gantry movements has allowed both supine and standing
      weight-bearing imaging of the lower extremity. There is an increasing amount of
      literature describing the use of weightbearing computed tomography in patients
      with foot and ankle disorders. To date, there is no review article summarizing
      this imaging modality in the foot and ankle. Therefore, we performed a systematic
      literature review of relevant clinical studies targeting the use of weightbearing
      computed tomography in diagnosis of patients with foot and ankle disorders.
      Furthermore, this review aims to offer insight to those with interest in
      considering possible future research opportunities with use of this technology.
      LEVEL OF EVIDENCE: Level V, expert opinion.

PMID- 29171284
TI  - Hamstring Autograft for Foot and Ankle Applications.
AB  - BACKGROUND: Hamstring tendon autografts may be used for foot and ankle surgeries,
      although reports on their effectiveness and morbidity in the foot and ankle
      literature are limited. We studied a cohort of patients who underwent hamstring
      harvest for foot and ankle applications, hypothesizing that morbidity to the knee
      would be limited. METHODS: We studied a cohort of patients who underwent
      hamstring autograft for foot or ankle applications by a fellowship-trained sports
      and foot and ankle surgeon since 2011. Thirty-seven patients underwent isokinetic
      strength testing using a dynamometer an average of 38 months postoperatively. The
      average patient age was 45 +/- 16 (range, 18-78) years, and 54% were women. Peak
      flexion and extension torque as well as flexion and extension torque at 30, 70,
      and 90 degrees of flexion were collected at 2 different testing speeds, 180 and
      300 degrees/s. t tests were used for all comparisons. RESULTS: At follow-up, 32
      patients (86%) reported no pain at the harvest site; the remaining 5 patients
      reported mild to moderate symptoms. No patients were dissatisfied, and all would
      recommend the surgery to someone else. Flexion strength at higher degrees of
      flexion was significantly lower compared with extension strength as well as
      compared with flexion strength at lower degrees of flexion, when testing was
      performed at lower speed ( P < 0.05). CONCLUSIONS: When used for foot and ankle
      surgery, hamstring autografts resulted in high patient satisfaction with minimal
      donor site morbidity. While knee flexion strength was decreased at higher degrees
      of flexion, this finding did not appear to be clinically significant. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 29171285
TI  - A human right to literacy education: Implications for serving Syrian refugee
      children.
AB  - Forty percent of Syrian refugees are younger than 12, and many have not attended
      school for up to five years, disadvantaging them academically, emotionally, and
      psychosocially. Article 19 of the Universal Declaration of Human Rights dictates
      "the right to freedom of opinion and expression...and to seek, receive and impart
      information and ideas...)". Resettled refugee children face the challenge of
      integration into majority-English school systems with limited ability to express
      themselves or linguistic means to access education. However, Syrian adults
      possess high rates of literacy and funds of knowledge that can promote an
      environment of learning in the home language. With incomplete language and
      literacy skills in their native Arabic, learning English for academics proves
      challenging. Without language and literacy instruction, refugee children
      experience a lower likelihood of class participation and a greater likelihood of
      social isolation or drop out. To inform speech-language pathologists and other
      educators, this literature review aims: (1) to apply second language learning
      concepts relevant to refugees, (2) to inform pedagogy specific to reading by
      highlighting cross-linguistic differences between Arabic and English, and (3) to
      illuminate strategies that families and educators of Arabic-speaking refugee
      students may employ to resume and promote language and literacy development.

PMID- 29171286
TI  - The first use of dementia care mapping in the care for older people with
      intellectual disability: a process analysis according to the RE-AIM framework.
AB  - INTRODUCTION: The aging of the population with intellectual disability (ID), with
      associated conseqences as dementia, creates a need for evidence-based methods to
      support staff. Dementia Care Mapping (DCM) is perceived to be valuable in
      dementia care and promising in ID-care. The aim of this study was to evaluate the
      process of the first use of DCM in ID-care. METHODS: DCM was used among older
      people with ID and care-staff in 12 group homes of six organisations. We obtained
      data on the first use of DCM in ID-care via focus-group discussions and face-to
      face interviews with: care-staff (N = 24), managers (N = 10), behavioural
      specialists (N = 7), DCM-ID mappers (N = 12), and DCM-trainers (N = 2). We used
      the RE-AIM framework for a thematic process-analysis. RESULTS: All available
      staff (94%) participated in DCM (reach). Regarding its efficacy, staff considered
      DCM valuable; it provided them new knowledge and skills. Participants intended to
      adopt DCM, by continuing and expanding its use in their organisations. DCM was
      implemented as intended, and strictly monitored and supported by DCM-trainers. As
      for maintenance, DCM was further tailored to ID-care and a version for individual
      ID-care settings was developed, both as standards for international use. To
      sustain the use of DCM in ID-care, a multidisciplinary, interorganisational
      learning network was established. CONCLUSION: DCM tailored to ID-care proved to
      be an appropriate and valuable method to support staff in their work with aging
      clients, and it allows for further implementation. This is a first step to obtain
      an evidence-based method in ID-care for older clients.

PMID- 29171287
TI  - When one childhood meets another - maternal childhood trauma and offspring child
      psychopathology: A systematic review.
AB  - BACKGROUND: Child maltreatment can have a long-term impact on mental health. Less
      is known about the consequences of child maltreatment on the next generation's
      psychological wellbeing. AIM: This systematic review aimed to synthesise the
      existing empirical literature on the association between a mother's history of
      maltreatment in her own childhood and her children's experiences of
      psychopathology, and to characterise potential mediating pathways. METHOD:
      Electronic database and hand searches yielded 12 studies, with a combined sample
      size of 45,723 mother-child dyads, which met criteria for inclusion in the
      review. RESULTS: There was evidence of an overall positive association between a
      mother's history of child maltreatment and her child's experience of emotional
      and behavioural difficulties across childhood and adolescence. Maternal
      psychological distress and poorer parenting practices were found to be key
      mediating pathways of this association. CONCLUSION: Children of mothers who were
      exposed to maltreatment in childhood appear to be at an increased risk for
      psychopathology. Mothers with traumatic childhood experiences should be offered
      improved access to psychological therapies and parenting programmes to help
      mitigate the potential impact of child maltreatment on future generations.

PMID- 29171289
TI  - Preclinical biomarker qualification.
AB  - Biomarkers are ubiquitously used within drug development programs in both
      nonclinical species and in humans to assess safety and efficacy of novel
      compounds. To routinely apply such novel biomarkers with certainty, a well
      defined data package is necessary for review and endorsement by regulatory
      agencies including the US Food and Drug Administration, European Medicines
      Agency, and Japanese Pharmaceuticals and Medical Devices Agency. This type of
      endorsement is known as regulatory qualification. Novel approaches are being
      applied to speed the process, lower the resource intensity, and increase the
      accessibility of biomarker qualification data and it is likely that consortia
      will continue to play a fundamental role in the qualification process by bringing
      together like-minded stakeholders focused on specific tools to accelerate drug
      development. This article will focus on learnings from the previous three
      nonclinical biomarker qualification projects, as well as discuss the progression
      of preclinical biomarker projects into the clinical qualification space and the
      current strategy for the use of nonclinical biomarker data in the translational
      qualification of clinical biomarkers; much like nonclinical information is used
      in the approval of drug development candidates. Impact statement This minireview
      provides an overview of the history of preclinical biomarker qualification by
      summarizing the three examples of this type of qualification with US Food and
      Drug Administration, European Medicines Agency, and Japanese Pharmaceuticals and
      Medical Devices Agency. In addition, an overview of the biomarker qualification
      process is included to educate key stakeholders with links to relevant white
      papers that provide information on current evidentiary considerations. The
      manuscript also provides new information on the evolution of the role that
      preclinical qualification plays in clinical qualification of biomarkers and the
      novel approaches that are being utilized to improve the process.

PMID- 29171290
TI  - The Flint water contamination crisis: the corrosion of positive peace and human
      decency.

PMID- 29171288
TI  - Featured article: Structure moderation of gut microbiota in liraglutide-treated
      diabetic male rats.
AB  - The change of gut microbiome is associated with a serious of metabolic disorders,
      such as diabetes. As a glucagon-like peptide 1 analogue, liraglutide is a potent
      antidiabetic drug in clinical practice. However, the effect of liraglutide on the
      community of gut microbiota is still unknown. We aimed to determine the influence
      of liraglutide on fecal microbiota in diabetic male rats. Five-week-old male
      Sprague-Dawley rats were fed with a control diet or a high-fat diet for four
      weeks. By injecting streptozotocin, the diabetic rat model was performed.
      Diabetic male rats were injected subcutaneously with a low dose of liraglutide
      (liraglutide 0.2 mg/kg/day), a high dose of liraglutide (liraglutide 0.4
      mg/kg/day), or normal saline for 12 weeks. Our data showed that liraglutide
      effectively prevented the development of diabetes in male rats. Pyrosequencing of
      the V3-V4 region of 16S rRNA genes manifested a remarkable transfer of gut
      microbiota construction in liraglutide-treated male rats compared with that of
      the diabetic male rats. Further analysis identified 879 liraglutide-treated
      specific operational taxonomic units. Some short-chain fatty acid (SCFA)
      producing bacteria, including Bacteroides, Lachnospiraceae, and probiotic
      bacteria, Bifidobacterium, were selectively enhanced in liraglutide-treated
      diabetic male rats. Lactobacillus was negatively correlated with fasting blood
      glucose. To sum up, our findings propose that the prevention of diabetes by
      liraglutide in the diabetic male rats may be associated with the structural
      change of the gut microbiota, inflammation alleviation, and abundantly elevated
      SCFA-producing bacteria in the intestine. Impact statement Our findings suggest
      that significant changes in gut microbiota are associated with liraglutide
      treatment on the diabetic male rats, including enrichment of short-chain fatty
      acid producers and probiotic bacteria. This may help alleviate systemic
      inflammation and contribute to the beneficial effects of liraglutide against
      diabetes.

PMID- 29171291
TI  - Concurrent validity of the Partners in Health scale against general self-rated
      health in chronic conditions: A short report.
AB  - The Partners in Health scale is a structurally valid measure of chronic condition
      self-management behaviours. This report describes a study that further evaluated
      construct validity of Partners in Health scale by assessing its relationship with
      a single-item measure of general self-rated health. The concurrent validity of
      the scale was demonstrated by a statistically significant association with
      general self-rated health in a population representative sample of people with
      chronic conditions.

PMID- 29171292
TI  - Two new steroidal saponins from the roots of Cynanchum limprichtii.
AB  - As a part of our continuing research for bioactive constituents from Cynanchum
      limprichtii Schltr., two new C21 steroidal glycosides limproside A (1) and
      limproside B (2) were isolated from the roots of Cynanchum limprichtii. Their
      structures were elucidated on the basis of 1D- and 2D-NMR spectroscopic data as
      well as HR-ESI-MS analysis. The cytotoxicity of two compounds against two
      selected human cancer cell lines was assayed.

PMID- 29171293
TI  - A new amino amidine derivative from the wood-decaying fungus Xylaria cf. cubensis
      SWUF08-86.
AB  - The secondary metabolites of Xylaria cf. cubensis SWUF08-86 fungus were
      investigated, and the chromatographic separation of the crude extracts yielded
      seventeen compounds. The structure elucidation by spectroscopic analysis
      including 1D and 2D NMR and the comparison of these data with literature, along
      with HREIMS spectrometry, revealed one new amino amidine derivative (1), together
      with five known simple cyclic dipeptide analogs, diketopiperazines (2-6) and
      eleven other known compounds, including one hemi-cycline (10), three aromatic
      derivatives (11-13), one sesquiterpene (14) and three sterols (15-17). The
      isolated compounds were screened for anticancer and anti-pathogenic bacterial and
      fungal activities. Based on this work, Xylaria cf. cubensis SWUF08-86 has proven
      to be a diverse secondary metabolites producer.

PMID- 29171294
TI  - Communication Capacity Research in the Majority World: Supporting the human right
      to communication specialist services.
AB  - Receipt of accessible and appropriate specialist services and resources by all
      people with communication and/or swallowing disability is a human right; however,
      it is a right rarely achieved in either Minority or Majority World contexts. This
      paper considers communication specialists' efforts to provide sustainable
      services for people with communication difficulties living in Majority World
      countries. The commentary draws on human rights literature, particularly Article
      19 of the Universal Declaration of Human Rights and the Communication Capacity
      Research program that includes: (1) gathering knowledge from policy and
      literature; (2) gathering knowledge from the community; (3) understanding speech,
      language and literacy use and proficiency; and (4) developing culturally and
      linguistically appropriate resources and assessments. To inform the development
      of resources and assessments that could be used by speech-language pathologists
      as well as other communication specialists in Fiji, the Communication Capacity
      Research program involved collection and analysis of data from multiple sources
      including 144 community members, 75 school students and their families, and 25
      teachers. The Communication Capacity Research program may be applicable for
      achieving the development of evidence-based, culturally and linguistically
      sustainable SLP services in similar contexts.

PMID- 29171295
TI  - Rural and remote speech-language pathology service inequities: An Australian
      human rights dilemma.
AB  - Access to healthcare is a fundamental human right for all Australians. Article 19
      of the Universal Declaration of Human Rights acknowledges the right to freedom of
      opinion and to seek, receive and impart information and ideas. Capacities for
      self-expression and effective communication underpin the realisation of these
      fundamental human rights. For rural and remote Australian children this
      realisation is compromised by complex disadvantages and inequities that
      contribute to communication delays, inequity of access to essential speech
      language pathology services and poorer later life outcomes. Localised solutions
      to the provision of civically engaged, accessible, acceptable and sustainable
      speech-language pathology services within rural and remote Australian contexts
      are required if we are to make substantive human rights gains. However, civically
      engaged and sustained healthcare can significantly challenge traditional
      professionalised perspectives on how best to design and implement speech-language
      pathology services that seek to address rural and remote communication needs and
      access inequities. A failure to engage these communities in the identification of
      childhood communication delays and solutions to address these delays, ultimately
      denies children, families and communities of their human rights for healthcare
      access, self-expression, self-dignity and meaningful inclusion within Australian
      society.

PMID- 29171296
TI  - The Support, Health, Activities, Resources, and Education program for early stage
      dementia: Results from a randomized controlled trial.
AB  - : Purpose A randomized controlled trial was conducted to test the effectiveness
      of the Support, Health, Activities, Resources, and Education Program. This six
      session psycho-educational program provides dyadic counseling for individuals in
      the early stages of dementia and their family caregivers. The goal is to prevent
      common problems in care that emerge during the course of dementia by (1) actively
      engaging the person with dementia in developing a balanced plan of future care
      with his/her caregiver, (2) increasing use of available services, (3) enhancing
      dyadic relationship functioning, (4) improving well-being, and (5) evoking
      satisfaction with components of the intervention. Design and methods Persons with
      early stage dementia ( n = 128) and their caregivers ( n = 128) were randomly
      assigned either to Support, Health, Activities, Resources, and Education Program
      or a control condition. Intervention efficacy was evaluated for completion of a
      care plan, use of services, dyadic relationship functioning, participant well
      being, and program satisfaction. Results Dyads in the treatment condition were
      able to construct a balanced care plan and increased their use of services.
      Dyadic functioning improved for one dimension (decreased emotional disruptions).
      Compared to the control condition, satisfaction with the intervention was higher
      for caregivers enrolled in Support, Health, Activities, Resources, and Education
      Program on four of five dimensions and one dimension for persons with dementia.
      IMPLICATIONS: Support, Health, Activities, Resources, and Education Program is a
      promising prevention approach that takes advantage of the early stage of dementia
      when both members of the dyad can participate fully in making decisions about
      later care.

PMID- 29171297
TI  - Perceptions of reciprocity in friendship by community dwelling people with mild
      to moderate dementia.
AB  - Positive social interaction is important for people with dementia, providing
      emotional and psychological benefits. Friendships may retain more reciprocal
      balance than caregiver relationships, which often become one-sided. This
      qualitative study investigates the meaning that friendship has for people with
      dementia, and how reciprocity relates to positive social identity. Individuals
      experiencing dementia were recruited from programs sponsored by a Midwest chapter
      of The Alzheimer's Association. In a face-to-face, one-time interview,
      participants were asked to share their perceptions about reciprocal friendship.
      Participants included 10 individuals who were primarily White, averaged 76 years
      old, with at least some college education. The data were analyzed using a
      phenomenological approach that revealed five themes of reciprocal friendship:
      recognizing the importance of longevity in friendship, helping one another is a
      normal part of friendship, feeling "alive" through the give and take in
      friendship, knowing somebody is there for them, and seeking security through
      friendship.

PMID- 29171298
TI  - Anti-platelet effects of vitamin supplements in age-related macular degeneration:
      an in vitro study.
AB  - OBJECTIVE: The purpose of this experimental study was to investigate the role of
      vitamin supplements (Ocuvite, Vitalux Omega, and Nutrof Total) as possible
      inhibitors of the onset of age-related macular degeneration (AMD). MATERIALS AND
      METHODS: The anti-aggregating effect of each vitamin was determined against four
      accumulative factors namely, platelet activating factor (PAF), adenosine
      diphosphate (ADP), thrombin receptor-activating peptide (TRAP), and arachidonic
      acid (AA) in the platelet rich plasma (PRP) of healthy volunteers. RESULTS:
      Ocuvite, Vitalux Omega, and Nutrof Total were more potent inhibitors against PAF
      and ADP compared to TRAP and AA. Among the three vitamins, Nutrof Total displayed
      more potent inhibitions against TRAP and AA, while against PAF and ADP all the
      three vitamins revealed similar IC50 values. CONCLUSIONS: The vitamins Ocuvite,
      Vitalux Omega, and Nutrof Total have anti-aggregating effects and therefore can
      be used against AMD in healthy volunteers.

PMID- 29171299
TI  - Whole body exposure of rats to sulfur mustard vapor.
AB  - Sulfur mustard (SM) is an incapacitating chemical warfare agent used in numerous
      conflicts around the world and it is still a major threat for both, army troops
      and civilians. To evaluate its multiple targets effects in experimental setup, a
      model of whole body exposure (WBE) to SM vapor was established in rats and its
      simultaneous effects on lungs and eyes as well as on general wellbeing were
      examined. Rats were exposed to SM vapor. Evaluation (up to 10 weeks post
      exposure) included body weight, general observation, blood counts and
      histological analysis. Results showed that following a latency-period of several
      hours, rats typical symptoms developed over a period of more than one week. The
      initial symptoms, characterized by swollen and erythematic nose, deteriorated
      into extensive rhinorrhea, eye closure, excessive lacrimation as well as rhonchi,
      wheezing and breathing difficulties. Alopecia and behavioral abnormality were
      also recorded. A weight loss of up to 40% was measured within one week with
      spontaneous recovery to baseline level within three weeks after exposure. Blood
      counts revealed leukopenia during the first three days post-exposure.
      Histological evaluation revealed a long lasting damage to the trachea, lungs and
      eyes. Thus, WBE to SM, was found to closely mimic the deleterious effects of SM
      on the sensitive tissues previously described in human victims during WWI and the
      Iran-Iraq war. The use of this animal model will enable comprehensive
      characterization of changes in biological processes that may lead to the
      development of therapeutic measures to ameliorate SM induced multi-system
      injuries.

PMID- 29171300
TI  - Tubeless Total Intravenous Anesthesia Spontaneous Ventilation for Adult
      Suspension Microlaryngoscopy.
AB  - INTRODUCTION: Maintaining spontaneous ventilation (SV) under total intravenous
      anesthesia (TIVA) without an endotracheal tube provides uninterrupted and
      unobstructed surgical access for suspension microlaryngoscopy (SML). This study
      describes the method and outcome of adults who underwent SML under tubeless TIVA
      SV. METHODS: Retrospective review of adults who underwent SML between June 2014
      and September 2016 using TIVA-SV without an endotracheal tube. RESULTS: Sixty-six
      cases in 36 patients were included with mean age of 50.6 years and 52.7% were
      female. Airway pathology included 41.6% subglottic or tracheal stenosis, 19.4%
      laryngeal lesion or mass, 16.7% glottic stenosis, 13.9% recurrent respiratory
      papilloma, and 8.3% supraglottic stenosis. Anesthesia was most commonly provided
      by continuous infusion of propofol and remifentanil (57.6%). Approximately half
      (53%) of cases received superior laryngeal nerve block. Average operative time
      was 72.9 minutes (range, 27-166 minutes). Eight cases required supplemental
      ventilation: 6 cases required transient endotracheal ventilation or mask
      ventilation, and 2 cases were converted to alternative ventilation. CONCLUSIONS:
      Total intravenous anesthesia is an attractive alternative to traditional
      endotracheal tube intubation, jet ventilation, or intermittent apneic ventilation
      for adult SML. During episodes of hypoventilation or desaturation, endotracheal
      ventilation, mask ventilation, or jet ventilation can effectively recover
      oxygenation.

PMID- 29171301
TI  - Hypolipidemic and cardioprotective effects of Ulva lactuca ethanolic extract in
      hypercholesterolemic mice.
AB  - CONTEXT: Hypercholesterolemia has significant cardiac consequences, since it is
      among the major risk factors of ischemic heart diseases. OBJECTIVE: The aim was
      searching the cardioprotective effect of chemical constituents from the sea
      lettuce Ulva lactuca upon hypercholesterolemic regime in mice. MATERIAL AND
      METHODS: Mice were randomly divided into three groups: untreated group,
      hypercholesterolemic group, and mice receiving 1% cholesterol associated with U.
      lactuca ethanolic extract. RESULTS: In vitro study demonstrated that algal
      extract has antioxidant efficacy attributable to the presence of phenolic
      compounds. Additionally, the alga alleviated cardiotoxicity, as shown by the
      improvement of haematological parameters, white cell viability, heart oxidative
      stress, plasma biochemical parameters and index of atherogenesis. Gene expression
      of the proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 significantly
      decreased in the heart of U. lactuca supplemented hypercholesterolemic animals.
      CONCLUSION: It was established that the green alga, thanks to its bioactive
      compounds, effectively counteracts cardiotoxic effects of hypercholesterolemic
      regime.

PMID- 29171302
TI  - Oxidatively rearranged cycloartane triterpenoids from the seeds of Pseudolarix
      amabilis.
AB  - One novel and eight known oxidatively rearranged cycloartane triterpenoids were
      isolated from the seeds of Pseudolarix amabilis. The structure of the new isolate
      was elucidated on extensive spectroscopic analyses. Results indicated that
      pseudolarolide Q (4) exhibited strong antimicrobial activity against Gram
      positive Staphylococcus aureus and Candida albicans at the MICs of 6.08 and 24.32
      MUM, respectively. Pseudolarolide I (2) showed the 11beta-HSD1 inhibitory
      property at the IC50 value of 34.5 nM.

PMID- 29171303
TI  - Flexor Hallucis Longus Muscle and Tendon Transfer for the Treatment of Achilles
      Tendon Wounds.

PMID- 29171304
TI  - An antifouling model from the sea: a review of 25 years of zosteric acid studies.
AB  - Many studies have shown that natural marine compounds can prevent biofouling by a
      broad spectrum of organisms without toxic effects, encouraging their use in
      antifouling (AF) coatings. Studies over the past 25 years of the natural product
      zosteric acid (ZA) are systematically organized in this review. ZA is a sulfated
      phenolic acid produced by the seagrass Zostera marina that has very promising AF
      potential against several micro- and macrofouling organisms. ZA was shown to have
      appropriate environmental fate parameters such as high water solubility, a low
      log P, low bioaccumulation, and no ecotoxicity, which demonstrated the potential
      of ZA as a safe AF agent. This review also highlights that ZA has been
      successfully incorporated into several types of coatings. The synthesis of
      analogs is also considered in this review, and it has allowed a better
      understanding of ZA structure-AF activity relationships and clarified the
      mechanism of action of ZA.

PMID- 29171306
TI  - Corrigendum.

PMID- 29171305
TI  - Serum interleukin-6 level is associated with response to infliximab in ulcerative
      colitis.
AB  - OBJECTIVES: Infliximab is effective in patients with ulcerative colitis (UC);
      however, one-third of patients do not respond and require additional therapies
      such as other biologic agents. Therefore, the aim of this study was to analyze
      the association between pro-inflammatory molecules and clinical efficacy to
      elucidate possible mechanisms for the non-response to infliximab to aid in
      treatment selection. MATERIALS AND METHOD: Patients with moderate-to-severe
      active UC receiving infliximab in our hospital between 2010 and 2016 for whom pre
      treatment serum samples were available were retrospectively evaluated. We
      analyzed the association between serum interleukin (IL)-6, tumor necrosis factor
      alpha (TNF-alpha) and soluble mucosal vascular addressin cell adhesion molecule-1
      (sMAdCAM-1) and the clinical efficacy of infliximab. The primary endpoint was
      clinical response at the end of the induction period. RESULTS: Forty-one patients
      were included in this study. After induction therapy, 27 patients (65.9%) showed
      a clinical response. Serum IL-6 levels were significantly lower in responders
      than in non-responders (p = .012), whereas no significant differences were noted
      in other factors including sMAdCAM-1 and TNF-alpha. Multivariate analysis
      identified that serum IL-6 level (odds ratio = 0.72; 95% confidence interval,
      0.54-0.96; p = .027) was independently associated with response to infliximab.
      CONCLUSIONS: Serum IL-6 level is associated with response to infliximab in UC.
      Elevated concentrations of IL-6 may provide insight to the mechanism of non
      response to infliximab.

PMID- 29171307
TI  - Pre-injury job characteristics and return to work among injured workers in South
      Korea: differences by socio-demographic and injury-related characteristics.
AB  - PURPOSE: This study examined the effect of pre-injury job characteristics on the
      odds of RTW outcomes for specific socio-demographic and injury-related
      characteristics among injured workers in South Korea. METHODS: This study
      employed first-wave data for 1993 participants from the Panel Study of Workers'
      Compensation Insurance. A two-step cluster analysis was conducted to profile pre
      injury job characteristics, including monthly wages, length of service, company
      size, contract type, and working hours. For each subsample selected by the
      characteristics of the independent variables, multinomial logistic regression
      analyses were performed to predict the odds ratio for being unemployed or working
      in a new firm versus returning to the pre-injury job, depending on cluster
      membership. RESULTS: Two clusters were identified with pre-injury job
      characteristics. Workers in the unstable employment cluster were more likely than
      were workers in the stable employment cluster to be unemployed or work in a new
      firm rather than return to the pre-injury job; this held for all socio
      demographic and injury-related characteristics. CONCLUSIONS: Our results showed a
      need to develop differential RTW strategies for injured workers in insecure jobs
      at the time of injury. Implications for rehabilitation Policymakers and
      rehabilitation practitioners need to take into account not only socio-demographic
      or injury-related characteristics but also working conditions at the time of
      injury when designing return-to-work programs for injured workers in South Korea.
      Injured employees in poor working conditions are relatively more vulnerable in
      the return-to-work process and deserve special attention and supports from the
      Korean government. The Korean government needs to review return-to-work policies
      for injured workers in unstable employment environment in the context of
      employment relationships rather than individual characteristics.

PMID- 29171308
TI  - Family-directed approach to brain injury (FAB) model: a preliminary framework to
      guide family-directed intervention for individuals with brain injury.
AB  - PURPOSE: This article proposes a theoretical framework to help professionals
      include family as active members in brain injury rehabilitation. A trend towards
      greater family involvement has lead to the development of family-collaboration
      models. However, current models appear to focus on information sharing rather
      than increasing the capability of family members. This article introduces a
      family-directed approach to brain injury model, which provides a theoretical
      framework for supporting family as facilitators of change. METHODS: Family
      collaboration models and literature regarding family experiences following brain
      injury and support needs are reviewed to identify the driving forces behind
      family engagement in rehabilitation, including effective professional-family
      relationships, and important factors in the delivery of education underpinned by
      evidence-based practices. RESULTS: The family-directed approach to brain injury
      model is based on principles of hope, family expertise, education/skill building,
      and family-directed intervention. CONCLUSIONS: The family-directed approach to
      brain injury model provides a theoretical framework for educating and training
      family members as facilitators in the management process: promoting competence
      rather than dependency on service systems. Guiding recommendations encourage
      professionals to reflect on the importance of their therapeutic relationships and
      their capacity to positively impact rehabilitation outcomes beyond the technical
      aspects of health care and treatment. Implications for Rehabilitation Training
      family members as facilitators in the rehabilitation process is suggested to
      reduce dependency on the service system, address families' unmet support needs,
      and to optimize rehabilitation outcomes for individuals with brain injury. The
      family-directed approach to brain injury model is proposed to guide the increased
      involvement of family as active members in the rehabilitation team and to define
      potential active ingredients in this process.

PMID- 29171310
TI  - The impact of speech and language problems in kindergarten on academic learning
      and special education status in grade three.
AB  - PURPOSE: This study addressed the implications of experiencing early speech
      language pathologies (SLPs) in kindergarten on special education needs (SEN) and
      academic outcomes in grade three. METHOD: Early Development Instrument (EDI)
      kindergarten data on development and the presence or absence of SLPs were matched
      with grade three school-system standardised tests of reading, writing and maths,
      and SEN classification in Ontario, Canada for 59 015 students. Children were
      classified as having a Persistent speech language pathology (SLP), Remittent SLP,
      Latent SEN or as a typically developing Control. RESULT: Even though 72.3% of
      children's SLPs remitted by grade three, kindergarten SLPs conveyed higher
      likelihood of having an SEN, and of lower achievement levels in grade three. The
      degree of impact varied between Persistent and Remittent groups. Children in the
      Latent group had lower scores in kindergarten on all five EDI domains than
      Control children. CONCLUSION: These population level results provide strong
      evidence to indicate that all children who present with an SLP in kindergarten
      face further academic challenges, even if their SLP resolves over time. Findings
      have implications for early intervention and treatment for children with early
      SLPs.

PMID- 29171309
TI  - What is the potential of nanolock- and nanocross-nanopore technology in cancer
      diagnosis?

PMID- 29171311
TI  - Lichen striatus successfully treated with oral cyclosporine.
AB  - Lichen striatus is an acquired, benign, linear inflammatory dermatosis
      characterized by a sudden skin eruption along Blaschko's lines that usually is
      not associated with specific etiologic agents. In most cases, it is a self
      limited dermatosis, but may relapse. Topical steroids are its first-line therapy,
      but this treatment is not always effective. We describe the case of a 45-year-old
      woman affected by a lichen striatus on her right limb resistant to topical
      corticosteroid therapy. The patient was successfully treated with cyclosporine (4
      mg/kg/die) for 4 weeks with no recurrence of the dermatitis during the subsequent
      1-year follow-up period.

PMID- 29171312
TI  - Acute lateral ankle sprain to chronic ankle instability: a pathway of
      dysfunction.
AB  - Lateral ankle sprains (LAS) have been reported as one of the most common
      musculoskeletal injuries observed in sports and in individuals who are
      recreationally active. Approximately 40% of individuals who sustain a LAS develop
      a condition known as chronic ankle instability (CAI). Years of research has
      identified numerous impairments associated with CAI such as decreases in range of
      motion (ROM), strength, postural control, and altered movement patterns during
      functional activities when compared to individuals with no LAS history. As a
      result, an impairment-based rehabilitation model was developed to treat the
      common impairments associated with CAI. The impairment-based rehabilitation model
      has been shown to be an effective rehabilitation strategy at improving both
      clinical and patient-oriented outcomes in patients with CAI. To date, the
      efficacy of an impairment-based rehabilitation model has not been evaluated in
      patients with an acute LAS. Prior to implementing an impairment-based model for
      the treatment of an acute LAS, similarities between impairments associated with
      acute LAS and CAI across the spectrum of the healing process is warranted.
      Therefore, the purpose of this review paper is to compare and contrast
      impairments and treatment techniques in individuals with an acute LAS, sub-acute
      LAS, and CAI. A secondary purpose of this review is to provide clinical
      commentary on the management of acute LAS and speculate how the implementation of
      an impairment-based rehabilitation strategy for the treatment of acute LAS could
      minimize the development of CAI. The main findings of this review were that
      similar impairments (decreased ROM, strength, postural control, and functional
      activities) are observed in patients with acute LAS, sub-acute LAS, and CAI,
      suggesting that the impairments associated with CAI are a continuation from the
      original impairments developed during the initial LAS. Therefore, the use of an
      impairment-based model may be advantageous when treating patients with an acute
      LAS.

PMID- 29171313
TI  - Correction to: Fulghesu et al., Very low dose of flutamide in the treatment of
      hyperandrogenism.

PMID- 29171314
TI  - Quality of life in Indian women with fertility problems as assessed by the
      FertiQoL questionnaire: a single center cross sectional study.
AB  - PURPOSE: Infertility and its treatment can significantly impact an individual's
      physical and psychological health; however, this has not been well-studied in the
      Indian population. This study aimed to assess the quality of life in women with
      infertility at a teaching hospital in Hyderabad, India. METHODS: In this cross
      sectional study of women with infertility, the quality of life was measured using
      the 'FertiQoL International' questionnaire (English/Hindi). RESULTS: The age
      ranged from 20 to 38 years and polycystic ovary syndrome was the most common
      cause of infertility. Core FertiQoL scores were analyzed in 215 women and
      Treatment FertiQoL in 156. The mean Total FertiQoL score in the study population
      was 66.1 (SD 13.0) and this overall score was not influenced by socio-demographic
      or infertility-specific factors. However, on subscale analysis, women who had
      living children and were university-educated had significantly better emotional
      scores while obese (>=35 kg/m2) women and those on ovulation induction treatment
      had poorer mind body and relational scores, respectively. Women with associated
      co-morbidities had worse quality of life on the Treatment Environment scale than
      those without. CONCLUSIONS: The results provide a baseline quality of life score
      in these women. Infertility had the greatest impact on the emotional domain.

PMID- 29171315
TI  - Suppressive effect of Okara on intestinal lipid digestion and absorption in mice
      ingesting high-fat diet.
AB  - Soymilk residue Okara is paid attention as a low-calorie foodstuff effective for
      the amelioration of obesity, and expected to have the potential ability to reduce
      calorie intake by suppressing the digestion and absorption of high-calorie
      nutrients in the intestinal tract. Then, the direct effect of Okara extract on
      lipase activity was examined, and this extract was shown to inhibit the enzyme
      activity. On the other hand, the spray-dried powder of Okara extract was
      suspended in a drinking water and given to mice fed with a high-fat diet.
      Consequently, Okara suspension was shown to reduce triglyceride (TG) levels in
      the blood, thus suggesting that Okara ingestion could suppress the digestion and
      absorption of lipids through the inhibition of lipase activity in the intestinal
      tract. Therefore, Okara is speculated to have the potential ability to prevent
      the excess intake of calories, thereby being effective and useful for the
      amelioration of metabolic syndrome.

PMID- 29171316
TI  - HBB: c.316-125A>G and HBB: c.316-42delC: Phenotypic Evaluations of Two Rare
      Changes in the Second Intron of the HBB Gene.
AB  - We report two very rare changes in the second intron of the HBB gene, a
      substitution at nucleotide (nt) 726 [IVS-II-726 (A>G) (beta+), NM_000518, HBB:
      c.316-125A>G] and a deletion of a cytosine at nt 809 [IVS-II-809 (-C) (beta),
      NM_000518, HBB: c.316-42delC] identified during the screening program for
      hemoglobinopathies in the resident Sicilian population. The purpose of this study
      was to evaluate the clinical implication of these rare changes, particularly in
      coinheritance with known mutations in the globin clusters, in order to conduct an
      appropriate genetic counseling for at-risk couples. Molecular analysis detected
      the first rare nt substitution in two cases in simple heterozygosity and in two
      cases in association with other known mutations on globin genes, while the
      deletion was identified in a pregnant woman, carrier of beta-thal, and in her
      fetus at prenatal diagnosis (PND) for hemoglobinopathies. The present study
      emphasizes the importance of sharing the observed changes in the globin gene
      cluster, especially in the case of new or rare undefined mutations, in order to
      facilitate the determination of their phenotypic expression and possible
      interactions with known molecular defects.

PMID- 29171318
TI  - Corrigendum.

PMID- 29171317
TI  - Basal blood DHEA-S/cortisol levels predicts EMDR treatment response in
      adolescents with PTSD.
AB  - OBJECTIVE: In literature, recent evidence has shown that the hypothalamic
      pituitary-adrenal (HPA) axis can be dysregulated in patients with post-traumatic
      stress disorder (PTSD) and HPA axis hormones may predict the psychotherapy
      treatment response in patients with PTSD. In this study, it was aimed to
      investigate changing cortisol and DHEA-S levels post-eye movement desensitization
      and reprocessing (EMDR) therapy and the relationship between treatment response
      and basal cortisol, and DHEA-S levels before treatment. METHOD: The study group
      comprised 40 adolescents (age, 12-18 years) with PTSD. The PTSD symptoms were
      assessed using the Child Depression Inventory (CDI) and Child Post-traumatic
      Stress Reaction Index (CPSRI) and the blood cortisol and DHEA-S were measured
      with the chemiluminescence method before and after treatment. A maximum of six
      sessions of EMDR therapy were conducted by an EMDR level-1 trained child
      psychiatry resident. Treatment response was measured by the pre- to post
      treatment decrease in self-reported and clinical PTSD severity. RESULTS: Pre- and
      post-treatment DHEA-S and cortisol levels did not show any statistically
      significant difference. Pre-treatment CDI scores were negatively correlated with
      pre-treatment DHEA-S levels (r: -0.39). ROC analysis demonstrated that the DHEA
      S/cortisol ratio predicts treatment response at a medium level (AUC: 0.703, p:
      .030, sensitivity: 0.65, specificity: 0.86). CONCLUSION: The results of this
      study suggested that the DHEA-S/cortisol ratio may predict treatment response in
      adolescents with PTSD receiving EMDR therapy. The biochemical parameter of HPA
      axis activity appears to be an important predictor of positive clinical response
      in adolescent PTSD patients, and could be used in clinical practice to predict
      PTSD treatment in the future.

PMID- 29171319
TI  - Cost-effectiveness of TYRX absorbable antibacterial envelope for prevention of
      cardiovascular implantable electronic device infection.
AB  - AIMS: Infection is a major complication of cardiovascular implantable electronic
      device (CIED) therapy that usually requires device extraction and is associated
      with increased morbidity and mortality. The TYRX Antibacterial Envelope is a
      polypropylene mesh that stabilizes the CIED and elutes minocycline and rifampin
      to reduce the risk of post-operative infection. METHODS: A decision tree was
      developed to assess the cost-effectiveness of TYRX vs standard of care (SOC)
      following implantation of four CIED device types. The model was parameterized for
      a UK National Health Service perspective. Probabilities were derived from the
      literature. Resource use included drug acquisition and administration,
      hospitalization, adverse events, device extraction, and replacement. Incremental
      cost-effectiveness ratios (ICERs) were calculated from costs and quality-adjusted
      life-years (QALYs). RESULTS: Over a 12-month time horizon, TYRX was less costly
      and more effective than SOC when utilized in patients with an ICD or CRT-D. TYRX
      was associated with ICERs of L46,548 and L21,768 per QALY gained in patients with
      an IPG or CRT-P, respectively. TYRX was cost-effective at a L30,000 threshold at
      baseline probabilities of infection exceeding 1.65% (CRT-D), 1.95% (CRT-P), 1.87%
      (IPG), and 1.38% (ICD). LIMITATIONS AND CONCLUSIONS: Device-specific infection
      rates for high-risk patients were not available in the literature and not used in
      this analysis, potentially under-estimating the impact of TYRX in certain
      devices. Nevertheless, TYRX is associated with a reduction in post-operative
      infection risk relative to SOC, resulting in reduced healthcare resource
      utilization at an initial cost. The ICERs are below the accepted willingness-to
      pay thresholds used by UK decision-makers. TYRX, therefore, represents a cost
      effective prevention option for CIED patients at high-risk of post-operative
      infection.

PMID- 29171320
TI  - The role of mitochondrial folate enzyme MTHFD1L in esophageal squamous cell
      carcinoma.
AB  - OBJECTIVE: The lack of novel therapeutic targets poses the major challenge to
      prolong survival and improve the quality of life for esophageal squamous cell
      carcinoma (ESCC). Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) plays
      critical roles in folate cycle maintenance. However, little information is
      available concerning the role of MTHFD1L in cancer cells, and no studies have
      addressed such issues in esophageal cancer. MATERIALS AND METHOD: Surgical cancer
      and adjacent normal esophageal tissues were obtained from patients with
      esophagectomy and esophagogastrostomy for ESCC. Western blot,
      immunohistochemistry and Quantitative RT-PCR were performed to evaluate protein
      and RNA expression levels of MTHFD1L. Knockdown of MTHFD1L expression was
      achieved by using short hairpin RNA. The effects of MTHFD1L silencing on ESCC
      cell proliferation and apoptosis were assessed by the MTT assay, Celigo assays,
      Annexin V FACS assay and Caspase-3/7 array in vitro. RESULTS: Twenty-three paired
      cancer and adjacent normal esophageal tissues from patients with ESCC were
      included in this study. MTHFD1L protein and RNA expression levels were
      significantly upregulated in ESCC tissue as compared with normal tissue. High
      expression of MTHFD1 was also detected in two esophageal cancer cell lines (TE-1
      and EC109). Knockdown of MTHFD1L expression inhibited the proliferation of TE-1
      cells, and the apoptosis was distinctly increased following shMTHFD1L infection.
      CONCLUSIONS: Our preliminary study highlighted for the first time that MTHFD1L
      might be involved in the development of ESCC, which may provide a new potential
      tumor-specific therapeutic targeting for anti-folate agents.

PMID- 29171321
TI  - Changes in medical student implicit attitudes following a health equity
      curricular intervention.
AB  - PURPOSE: This study assessed the: (1) effect of an LGBTQI + health equity
      curriculum (eQuality) on implicit attitudes among first (M1) and second year (M2)
      medical students and (2) utility of dedicated time to explore implicit bias.
      METHOD: Implicit biases were assessed at baseline using implicit association
      tests (IAT) for all M2s and a random sample of first years (M1A). These students
      were then debriefed on strategies to mitigate bias. Following eQuality, all M1
      and M2s completed post-intervention IATs. The remaining first years (M1B) were
      then debriefed. Paired sample t-tests assessed differences between pre/post.
      Independent sample t-tests assessed differences in post-IATs between M1 groups.
      RESULTS: IATs indicated preferences for "Straight," "White," and "Thin" at both
      pre and post. M2s demonstrated statistically significant improvements pre to post
      for sexuality (p = 0.01) and race (p = 0.03). There were significant differences
      in post-intervention IAT scores between M1As who received the IAT and debriefing
      prior to eQuality and M1Bs for sexuality (p = 0.002) and race (p = 0.046). There
      were no significant changes for weight. CONCLUSION: eQuality reduced implicit
      preference for "Straight" and "White." Differences in M1 post-intervention IAT
      scores between groups suggest dedicating time to debrief implicit attitudes
      enhances bias mitigation.

PMID- 29171322
TI  - Graft fixation influences revision risk after ACL reconstruction with hamstring
      tendon autografts.
AB  - Background and purpose - A large number of fixation methods of hamstring tendon
      autograft (HT) are available for anterior cruciate ligament reconstruction
      (ACLR). Some studies report an association between fixation method and the risk
      of revision ACLR. We compared the risk of revision of various femoral and tibial
      fixation methods used for HT in Scandinavia 2004-2011. Materials and methods - A
      register-based study of 38,666 patients undergoing primary ACLRs with HT, with
      1,042 revision ACLRs. The overall median follow-up time was 2.8 (0-8) years.
      Fixation devices used in a small number of patients were grouped according to
      design and the point of fixation. Results - The most common fixation methods were
      Endobutton (36%) and Rigidfix (31%) in the femur; and interference screw (48%)
      and Intrafix (34%) in the tibia. In a multivariable Cox regression model, the
      transfemoral fixations Rigidfix and Transfix had a lower risk of revision (HR 0.7
      [95% CI 0.6-0.8] and 0.7 [CI 0.6-0.9] respectively) compared with Endobutton. In
      the tibia the retro interference screw had a higher risk of revision (HR 1.9 [CI
      1.3-2.9]) compared with an interference screw. Interpretation - The choice of
      graft fixation influences the risk of revision after primary ACLR with hamstring
      tendon autograft.

PMID- 29171324
TI  - Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors
      after high-dose therapy with autologous stem cell transplantation.
AB  - BACKGROUND: Obstructive and restrictive dysfunction in long-term lymphoma
      survivors (LSs) after high-dose therapy with autologous stem-cell transplantation
      (HDT-ASCT) has not been addressed systematically previously. MATERIAL AND
      METHODS: LSs treated in Norway 1987-2008 with HDT-ASCT who performed spirometry,
      measurement of static lung volumes and echocardiography 2012-2014 at either Oslo
      or St. Olavs University Hospitals was eligible. Smoking data were recorded by
      questionnaire. Treatment data were collected from medical records or hospital
      databases. Factors associated with obstructive and restrictive impairments
      (dichotomous outcomes) were examined by Poisson regression. Linear regression
      with the margins post-estimation command was used to derive adjusted mean values
      of forced expiratory volume in 1 s (FEV1). We used the normative reference data
      recommended by the European Respiratory Society for calculating percent predicted
      values. RESULTS: A total of 226 LSs were studied, of whom 11.5 and 5.8% had
      obstructive and restrictive impairment, respectively. For women and men, mean
      FEV1 was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that
      predicted from norms, respectively. In multivariable regression analyses,
      cumulative doxorubicin dose (400-775 mg/m2) and current smoking were associated
      with increased risk of obstructive impairment, and chest RT (>13-66 Gy) was
      associated with increased risk of restrictive impairment. Currently smoking LSs
      within the highest doxorubicin category (400-775 mg/m2), had the lowest adjusted
      mean FEV1. CONCLUSIONS: Despite intensive cancer treatment, our analysis showed
      modest reductions in obstructive parameters among long-term LSs after HDT-ASCT
      compared to normative reference data. To limit obstructive impairments in LSs
      after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed
      towards patients who have received high cumulative doses of doxorubicin.

PMID- 29171325
TI  - New perspectives in stress research: 2016 neurobiology of stress workshop.

PMID- 29171326
TI  - The antitumour effects of eudesmin on lung cancer by inducing apoptosis via
      mitochondria-mediated pathway in the tumour cells.
AB  - CONTEXT: Limonoids possess broad range of biological activities, including
      antitumour, antimicrobial and antioxidant activities, etc. Eudesmin (EDN) is a
      type of limonoid which also possesses various activities. However, there is no
      report on the antitumour lung cancer (LC) activities of this compound. OBJECTIVE:
      The present study investigates the antitumour effects of EDN and its potential
      molecular mechanisms. MATERIALS AND METHODS: The in vitro antitumour effects of
      EDN on LC A549 cells were evaluated by using MTT assay. The in vivo antitumour
      effects were investigated on a xenograft athymic nude mouse model. The mice were
      administered orally with EDN (10, 20 and 40 mg/kg) once daily for 28 days.
      Effects of EDN on apoptosis-related or signalling proteins (Bcl-2, Bax, caspase
      3, caspase-9, P53, Akt and JNK) were assayed by western blot analysis. RESULTS:
      EDN showed significant inhibitory effects on the growth of LC A549 cells in vitro
      with the half maximal inhibitory concentration (IC50) of 18.3 MUM. By treating
      with EDN (10, 20 and 40 MUM), expression of caspase-3, caspase-9, Bax, P53 and
      phosphorylated JNK in A549 cells were significantly upregulated, whereas
      expression of Bcl-2 and Akt phosphorylation were significantly down-regulated.
      Interestingly, EDN-induced apoptosis could be attenuated by JNK inhibitor. In
      addition, in vivo experiments also indicated EDN (10, 20 and 40 mg/kg) had
      significant antitumour effects (p < 0.01) on nude mice. CONCLUSIONS: Overall, the
      results indicated that EDN possesses significant antitumour effects on LC and the
      possible mechanism might be related to induction of mitochondria-mediated
      apoptosis.

PMID- 29171327
TI  - A review of the evidence for endocrine disrupting effects of current-use
      chemicals on wildlife populations.
AB  - This review critically examines the data on claimed endocrine-mediated adverse
      effects of chemicals on wildlife populations. It focuses on the effects of
      current-use chemicals, and compares their apparent scale and severity with those
      of legacy chemicals which have been withdrawn from sale or use, although they may
      still be present in the environment. The review concludes that the effects on
      wildlife of many legacy chemicals with endocrine activity are generally greater
      than those caused by current-use chemicals, with the exception of
      ethinylestradiol and other estrogens found in sewage effluents, which are causing
      widespread effects on fish populations. It is considered that current chemical
      testing regimes and risk assessment procedures, at least those to which
      pesticides and biocides are subjected, are in part responsible for this
      improvement. This is noteworthy as most ecotoxicological testing for regulatory
      purposes is currently focused on characterizing apical adverse effect endpoints
      rather than identifying the mechanism(s) responsible for any observed effects.
      Furthermore, a suite of internationally standardized ecotoxicity tests sensitive
      for potential endocrine-mediated effects is now in place, or under development,
      which should ensure further characterization of substances with these properties
      so that they can be adequately regulated.

PMID- 29171329
TI  - Defining curricular priorities for student-as-teacher programs: A National Delphi
      Study.
AB  - BACKGROUND: "Student-as-Teacher" (SaT) programs have been growing in number to
      prepare medical students for their teaching roles in residency and beyond, but it
      remains unknown what content areas should be covered in SaT curricula. AIM: To
      determine five to ten "essential" content areas for inclusion in SaT curricula
      using expert opinion. METHODS: Using a three-round Delphi process, moderators
      iteratively surveyed a panel of 28 medical educators (25 academy directors and
      three individuals identified as having expertise in undergraduate medical
      education) representing 25 medical schools in the United States. This "SaT Delphi
      Working Group" was tasked with rating topics for inclusion in SaT curricula on a
      3-point scale (i.e. 1. "essential," 2. "important, but not essential" 3. "not
      important"). Topics achieving >=70% consensus as "essential," "important" or "not
      important" were accepted by the moderators and removed from subsequent rounds.
      RESULTS: Hundred per cent response rate (n = 28) was achieved for all survey
      rounds. Five content areas reached consensus as "essential" for inclusion in a
      SaT curriculum: feedback, bedside teaching and clinical precepting, small-group
      teaching, case-based teaching and professionalism as a medical educator.
      CONCLUSION: This consensus from a group of leaders in medical education is a
      first step toward the implementation of more developmentally-appropriate SaT
      competencies.

PMID- 29171330
TI  - Corrigendum to: Godwin Y, Wheble GAC and Feig C. Assessment of the presence of
      independent flexor digitorum superficialis function in the small fingers of
      professional string players: Is this an example of natural selection? J Hand Surg
      Eur. 2013, 39: 93-100.
AB  - The corresponding author details for the above article have been modified. The
      online version of the article has been updated.

PMID- 29171328
TI  - Emerging roles of DROSHA beyond primary microRNA processing.
AB  - DROSHA is the catalytic subunit of the Microprocessor complex, which initiates
      microRNA (miRNA) maturation in the nucleus by recognizing and cleaving hairpin
      precursors embedded in primary transcripts. However, accumulating evidence
      suggests that not all hairpin substrates of DROSHA are associated with the
      generation of functional small RNAs. By targeting those hairpins, DROSHA
      regulates diverse aspects of RNA metabolism across the transcriptome, serves as a
      line of defense against the expression of potentially deleterious elements, and
      permits cell fate determination and differentiation. DROSHA is also versatile in
      the way that it executes these noncanonical functions, occasionally depending on
      its RNA-binding activity rather than its catalytic activity. Herein, we discuss
      the functional and mechanistic diversity of DROSHA beyond the miRNA biogenesis
      pathway in light of recent findings.

PMID- 29171331
TI  - The Y-V plasty for first web space release.

PMID- 29171332
TI  - Interleukin-6 as one of the potential mediators of immune-related adverse events
      in non-small cell lung cancer patients treated with immune checkpoint blockade:
      evidence from a case report.

PMID- 29171333
TI  - Twelve tips for implementing effective service learning.
AB  - Service learning is an educational methodology that facilitates transformation of
      students' knowledge, attitudes and attitudes around holistic care through work
      with community organizations. To implement academically, defensible service
      learning requires faculty endorsement, consideration of course credit, an
      enthusiastic champion able to negotiate agreements with organizations,
      organizations' identification of their own projects so they are willing to both
      fund and supervise them, curricular underpinning that imparts the project skills
      necessary for success, embedding at a time when students' clinical identity is
      being formed, small packets of curriculum elements delivered "just in time" as
      students engage with their project, flexible online platform/s, assessment that
      is organically related to the project, providing cross cultural up-skilling, and
      focused on the students' responsibility for their own product. The result is a
      learning experience that is engaging for medical students, links the university
      to the community, and encourages altruism which is otherwise reported to decline
      through medical school.

PMID- 29171335
TI  - The cardiovascular benefits of indiscriminate supplementation of omega-3 fatty
      acids; meta-analysis and decision-making approach.
AB  - AIM: The meta-analysis was conducted to estimate of the cardiovascular benefits
      of indiscriminate supplementation of omega-3 capsules. The results, expressed in
      terms of quality adjusted life years (QALY) intuitively understood by the general
      public, can be the basis for the (personal) decision on whether to take omega-3
      supplements. METHODS: The results of meta-analysis of eight double-blind, placebo
      controlled clinical trials are expressed in terms of QALY, using the Markov model
      and Monte Carlo simulations. RESULTS: Omega-3 supplementation results in a 8%
      decrease of the risk of cardiac death, unless the patients are treated by
      statins. Results indicate that omega-3 supplementation may prolong QALY by about
      a month. Old people gain less, whereas DM-2 patients and people with history of
      CV events gain more. DISCUSSION: Our analysis yielded an algorithm for estimating
      benefit from omega-3 supplementation, based on the age and the individual risk of
      CV events of the patient.

PMID- 29171334
TI  - G-Quadruplexes influence pri-microRNA processing.
AB  - RNA G-Quadruplexes (G4) have been shown to possess many biological functions,
      including the regulation of microRNA (miRNA) biogenesis and function. However,
      their impact on pri-miRNA processing remains unknown. We identified G4 located
      near the Drosha cleavage site in three distinct pri-miRNAs: pri-mir200c, pri
      mir451a, and pri-mir497. The folding of the potential G4 motifs was determined in
      solution. Subsequently, mutations disrupting G4 folding led to important changes
      in the mature miRNAs levels in cells. Moreover, using small antisense
      oligonucleotides binding to the pri-miRNA, it was possible to modulate, either
      positively or negatively, the mature miRNA levels. Together, these data
      demonstrate that G4 motifs could contribute to the regulation of pri-mRNA
      processing, a novel role for G4. Considering that bio-informatics screening
      indicates that between 9% and 50% of all pri-miRNAs contain a putative G4, these
      structures possess interesting potential as future therapeutic targets.

PMID- 29171336
TI  - Promoting health and well-being in the context of the United Nations Sustainable
      Development Agenda.

PMID- 29171337
TI  - Boys With Duchenne Muscular Dystrophy: 1-Year Locomotor Changes in Relation to a
      Control Group.
AB  - We compared the timed performance and compensatory movements of 32 boys (mean age
      = 10.0 years) with Duchenne muscular dystrophy (DMD) and 38 healthy boys (mean
      age = 9.2 years) on 10 -meter walking and four-step stair work (climbing and
      descending). Dependent measures were digital scores on the Functional Evaluation
      Scale for DMD obtained by watching the boys on film. Groups were compared
      initially and after 6 and 12 months, using General Linear Models analysis (for
      two groups and three assessments). Results showed no significant timed
      performance differences between groups on 10 -m walking at the initial
      assessment; but boys with DMD showed longer times after 6 and 12 months, and boys
      with DMD engaged in more compensatory movements while walking. For stair
      climbing, boys with DMD were significantly slower than healthy controls when both
      climbing and descending steps in all assessments.

PMID- 29171338
TI  - Effects of a Dual Swallow-Attention Task on Swallow and Cognitive Performance
      Measures.
AB  - Research evidence has mounted that cognitive distracters can be detrimental to
      concurrent motor performance. Yet, few investigations have probed how cognitive
      distracters might impact dysphagia (swallowing impairment) though secondary
      tasks, like watching television, now compete with swallowing in a 21st-century
      lifestyle. Accordingly, we sought to determine whether cognitive distracters
      while swallowing alter swallowing or cognitive performance among healthy young
      adults. Participants were 30 healthy volunteers 18-24 years of age who underwent
      a baseline swallow task (BST), a baseline cognitive task (BCT), and a dual task
      (DT) in randomized order. The BST consisted of consuming 100 mL of (a) luke warm
      water (LWW) and (b) carbonated sweet water (CSW). The BCT involved pressing a key
      to indicate speed or reaction time for completing a number recognition task. In
      the DT condition, swallow and cognitive tasks were performed concurrently.
      Volume/swallow (V/S), time/swallow (T/S), and swallow capacity (SC) indices were
      derived for the swallow task and reaction time in milliseconds reflected
      cognitive task performance. On comparison between baseline and the DT condition,
      there was a decrease in V/S, increase in T/S, and an overall reduction in SC
      across LWW and CSW. Moreover, there was a slower cognitive reaction time in the
      DT condition. A significant repeated measures of ANOVA difference was noted
      between baseline and DT conditions ( p < .001). We conclude that swallowing
      should not be done in the presence of cognitively distracters.

PMID- 29171339
TI  - Fidelity of Occupational Performance Coaching: Importance of Accuracy in
      Intervention Identification.
AB  - Establishing fidelity processes and measures is an important step in the
      development of interventions. Accurate referencing, naming of interventions and
      robust discussion of deviations from the theories, methods or terminology
      underpinning interventions support the fidelity of future applications of
      interventions in research and clinical settings. This commentary clarifies the
      establishment of fidelity for Occupational Performance Coaching (OPC) in relation
      to a recent article on this topic by Dunn and colleagues. Fundamental flaws in
      the referencing, labelling, theoretical underpinnings and methods inaccurately
      described as OPC are outlined. Guidance in establishing fidelity for future
      applications of OPC is provided.

PMID- 29171340
TI  - Measurement properties and feasibility of the Loughborough soccer passing test: A
      systematic review.
AB  - The purpose of this paper was to systematically review the literature and examine
      the research methodological quality, measurement properties and feasibility of
      the Loughborough Soccer Passing Test (LSPT). Databases were searched up to June
      2017. Twenty five studies fulfilled the eligibility criteria. The main
      methodological limitations of the studies were the small sample size and the lack
      of information on participants and eligibility criteria. Results showed that test
      retest reliability of the LSPT was moderate to excellent. Good discriminative
      validity was found between playing levels and ages. The LSPT was positively
      correlated with sprint, dribbling, and agility test; however, a weak correlation
      was established with in-game performance. Test responsiveness (an ability to
      detect change over time) to some external interventions was observed in studies.
      Adjusted Cronbach's alpha (alpha = 0.67), smallest worthwhile change (SWC = 0.8
      3.8) and minimal detectable change (MDC50 = 1.9-11.3) were calculated based on
      available data. The findings indicate that the LSPT has acceptable test-retest
      reliability and discriminative validity. However, it may not be a feasible and
      effective way to interpret the intra-individual change of skill performance in
      practice. Future work should be undertaken to establish additional measurement
      properties of the LSPT, and to improve its practical feasibility.

PMID- 29171341
TI  - Diagnosis of a tympanic paraganglioma with CT perfusion imaging: a technical note
      and case description.
AB  - Paragangliomas can be diagnosed accurately using magnetic resonance imaging and
      dynamic four-dimensional magnetic resonance angiography. Four-dimensional imaging
      uses the highly vascularised structure of these tumours, which results in a
      homogenous capillary blush and usually, due to the arteriovenous shunting, in an
      early draining vein. By these features the tumour can be differentiated from
      other neoplasms. The authors describe a case of a paraganglioma localised in the
      middle ear of an elderly patient. Magnetic resonance contraindications led to
      preoperative diagnostics with high resolution computed tomography of the temporal
      bone and additionally computed tomography perfusion imaging instead of magnetic
      resonance imaging with four-dimensional magnetic resonance angiography. Using the
      computed tomography perfusion dataset, regions of interest were placed in the
      carotid artery, the sigmoid sinus and the tympanic mass. In the computer-assisted
      analysis the tumour showed late arterial enhancement and delayed wash-out
      compared to the enhancement curves of the carotid artery and the sigmoid sinus.
      This corresponded to the highly vascularised nature of a paraganglioma. On
      postoperative follow-up imaging computed tomography perfusion showed almost no
      enhancement of a small residual tympanic mass, which was then considered to be
      granulation tissue. In conclusion, in the case of magnetic resonance
      contraindications the preoperative diagnosis of tympanic paraganglioma can be
      made using computed tomography imaging criteria alone. Computed tomography
      perfusion imaging may be helpful in these cases to detect residual or recurrent
      tumour.

PMID- 29171343
TI  - Structure-activity relationship on DNA binding and anticancer activities of a
      family of mixed-ligand oxidovanadium(V) hydrazone complexes.
AB  - The title family of mixed-ligand oxidovanadium(V) hydrazone complexes are
      [VVO(HL1)(hq)] (1) and [VVO(HL2)(hq)] (2), where (HL1)2- and (HL2)2- are the
      dinegative form of 2-hydroxybenzoylhydrazone of acetylacetone (H3L1) and
      benzoylacetone (H3L2), respectively, and hq- is the mononegative form of 8
      hydroxyquinoline (Hhq). Complexes were used to determine their binding constant
      with CT DNA using various spectroscopic techniques namely, electronic absorption,
      fluorescence and circular dichroism spectroscopy. The binding constant values
      suggest the intercalative mode of binding with the CT DNA and follow the order: 2
      > 1. The bulky size as well as electron withdrawing property of the phenyl group
      (which is present in the beta-diketone part of the hydrazone moiety in complex 2
      in place of a CH3 group in complex 1) is responsible for the higher activity of 2
      than 1. Complexes were screened for cytotoxic activity on cervical cancer cells
      and were found to be potentially active (IC50 value for 1 and 2 is 33 and 29 MUM,
      respectively), even better than the widely used cis-platin (IC50 = 63.5 MUM) and
      carboplatin (IC50 =  > 200 MUM) which is evident from the respective IC50 value.
      Nuclear staining experiment suggests that these complexes kill the SiHa cancer
      cells through apoptotic mode. The molecular docking study also suggested the
      intercalative mode of binding of these complexes with CT DNA and HPV 18 DNA.

PMID- 29171344
TI  - Sex differences in postprandial lipaemia after acute high-intensity interval
      running in young people.
AB  - Acute exercise reduces postprandial triacylglycerol concentrations ([TAG]) in
      boys and girls; however, it is not known whether between-sex differences exist in
      response to exercise. Fifteen boys (mean(SD): 11.8(0.4) years) and sixteen girls
      (12.1(0.7) years) completed two, 2-day conditions. On day 1, participants rested
      (CON) or completed 10 * 1 min high-intensity interval runs at 100% maximal
      aerobic speed with 1 min recovery (HIIR). On day 2, participants consumed a
      standardised breakfast and lunch over a 6.5-h period during which seven capillary
      blood samples were collected. Based on ratios of the geometric means (95% CI for
      ratios), fasting [TAG] was 32% lower in boys than girls (-44 to -18%, ES = 1.31,
      P < 0.001), and 12% lower after HIIR than CON (-18 to -5%, ES = 0.42, P = 0.003);
      the magnitude of reduction was not significantly different between the sexes (8%
      (ES = 0.36) vs. 15% (ES = 0.47), respectively; P = 0.29). The total area under
      the [TAG] versus time curve was 27% lower in boys than girls (-40 to -10%, ES =
      1.02, P = 0.005), and 10% lower after HIIR than CON (-16 to -5%, ES = 0.36, P =
      0.001); the magnitude of reduction was similar between the sexes (11% (ES = 0.43)
      vs. 10% (ES = 0.31), respectively; P = 0.87). The small-moderate reduction in
      postprandial [TAG] after HIIR was similar between the sexes.

PMID- 29171346
TI  - Computational and in vitro insights on snake venom phospholipase A2 inhibitor of
      phytocompound ikshusterol3-O-glucoside of Clematis gouriana Roxb. ex DC.
AB  - Ikshusterol3-O-glucoside was isolated from Clematis gouriana Roxb. ex DC. root. A
      structure of the isolated compound was determined on the basis of various
      spectroscopic interpretations (UV, NMR, FTIR, and GC-MS-EI). This structure was
      submitted in the PubChem compound database (SID 249494133). SID 249494133 was
      carried out by density functional theory calculation to observe the chemical
      stability and electrostatic potential of this compound. The absorption,
      distribution, metabolism, and excretion property of this compound was predicted
      to evaluate the drug likeness and toxicity. In addition, molecular docking,
      quantum polarized ligand docking, prime MMGBSA calculation, and induced fit
      docking were performed to predict the binding status of SID 249494133 with the
      active site of phospholipase A2 (PLA2) (PDB ID: 1A3D). The stability of the
      compound in the active site of PLA2 was carried out using molecular dynamics
      simulation. Further, the anti-venom activity of the compound was assessed using
      the PLA2 assay against Naja naja (Indian cobra) crude venom. The results strongly
      show that Ikshusterol3-O-glucoside has a potent snake-venom neutralizing capacity
      and it might be a potential molecule for the therapeutic treatment for
      snakebites.

PMID- 29171347
TI  - "Watchful? For sure!" - Health professionals as family carers and their roles in
      patient safety
AB  - Background: Little is known about family caregivers in the context of adverse
      events that occur during the care of their significant others. Nurses as family
      caregivers can draw on expert specific knowledge and nursing skills. Aim: To
      explore how family carers who are also trained nurses experience and deal with
      adverse events that occur during the care of their significant others. Method: As
      part of a larger research project using a sequential mixed methods design, 30
      semi-structured interviews were conducted with health professionals, who were
      also family caregivers, of whom 20 were qualified nurses. All interviews were
      theoretically coded, dimensionalized and contextualized. Based on the nurses'
      data a model was developed. Results: The model illustrates the dilemma the
      interviewed nurses experienced when they need to deal with safety-relevant
      problems. As family caregivers with expert knowledge and skills, they were
      vigilant in surveilling the care provided. They were quick to identify risks and
      vulnerable points in the system of care being delivered. However, before taking
      action, they carefully considered the advantages and disadvantages of
      intervening, and also whether or not to admit that they were health care
      professionals. Conclusions: In the case of events relevant to the health and
      safety of their significant others, family carers who are trained nurses are most
      likely to use their expert knowledge, in situations with a perceived high risk to
      health, to minimise the potential harm.

PMID- 29171349
TI  - ?

PMID- 29171348
TI  - Safe swallowing and communicating for ventilated intensive care patients with
      tracheostoma: implementation of the Passy Muir speaking valve
AB  - Background: Between 4 to 45 % of intensive care patients suffer from prolonged
      ventilator dependence. Due to impeded weaning, verbal communication is
      impossible. The tracheal cannula affects breathing and swallowing. The Passy Muir
      speaking valve (PMV) allows patients on ventilators to speak. It counteracts
      pharyngeal as well as laryngeal desensitization and prevents an insufficient
      swallowing reflex. Aim and methods: To implement the PMV, we conducted a
      multiprofessional practice- and quality development project. The objective was to
      ensure safe swallowing and communicating for ventilated patients with
      tracheostoma. Results: Intensive care nurses, doctors and physiotherapists
      assessed patient safety as being high. In nine patients with 51 PMV applications,
      we observed three undesirable events in terms of dyspnea and oxygen desaturation.
      On one occasion, it was necessary to remove the PMV. Conclusion: A combination of
      mandatory training for the entire treatment team, presence of two professionals
      during PMV application, and a newly developed guiding document resulted in a high
      level of patient safety. By means of PMV, ventilated intensive care patients are
      able to communicate verbally and to swallow better. Complications can be
      identified early and solved effectively.

PMID- 29171350
TI  - ?

PMID- 29171351
TI  - ?

PMID- 29171352
TI  - The one-week and six-month reliability and variability of three-dimensional
      tibial acceleration in runners.
AB  - Tibial acceleration is a surrogate measure for impact loading and lower limb
      fatigue injury in runners. Triaxial accelerometers may offer reliable and
      practical measurement of resultant peak tibial acceleration (PTA). With such
      potential in mind, this study examined variability and measurement reliability of
      tibial acceleration in 14 runners at baseline at one week, and eight of the
      runners again at six months. Triaxial accelerometers were attached to the distal
      tibiae of runners before they ran on a treadmill for two minutes each, at speeds
      of 2.7, 3.0, 3.3 and 3.7 m/s in standardised shoes. Resultant PTAs were
      calculated for each speed and session. Reliability outcomes were presented as
      percentage change and effect sizes. Variability outcomes included intraclass
      correlation coefficients and the typical error of the measurement. Smallest
      worthwhile change and performance/noise ratio were also calculated. While runners
      demonstrated marginally lower reliability and higher variability over six months,
      compared to one week, in all cases the measures of reliability and variability
      were of 'good' to 'moderate' reliability, and 'small' to 'moderate' variability
      using magnitude-based inferences. We can be confident that resultant PTA can be
      used with runners to assess and monitor their impacts throughout a six-month
      intervention.

PMID- 29171353
TI  - The neuro control of the ovarain cycle - a hypothesis.
AB  - Since more than 100 years, it is known that pituitary function depends upon the
      function of higher centers in the brain. It was already assumed at this time that
      pituitary extracts could influence the gonads and postulated that their use could
      have practical applications. In 1926, the 'gonadal principle' was discovered
      revealing the regulation of ovarian function by the pituitary. The two pituitary
      hormones were called 'Prolan A' and 'Prolan B' which are responsible for ovarian
      function especially secretion of the hormones: 'lutein' and 'foliculin'. If the
      names of Prolan A and B are changed to follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH), and the names of foliculin and lutein to estrogen and
      progesterone, it becomes obvious that the pituitary-gonadal relationship, as we
      know it today, was first described in 1930. Then, the next step was the
      isolation, sequence and synthesis of gonadotropin releasing hormone (GnRH)
      responsible for the secretion of gonadotropins (Gn). It could be shown that GnRH
      pulse frequency has differential effects on Gn secretion: low-frequency pulses of
      GnRH stimulate preferentially FSH and high frequency LH secretion. The pulse
      frequency control depends from a subpopulation of kisspeptin neurons within the
      infundibular region of the hypothalamus with coexpression of neurokinin B and
      dynorphin A - KNDy neurons showing a negative feedback to estrogen. A second
      group of kisspeptide neurons in the rostral periventricular area of the third
      ventricle is devoid of neurokinin-B and dynorphin, mediates positive feedback
      from estrogen and so induces the midcycle LH-surge. Therefore, the variability in
      the frequency and amplitude of GnRH pulsatility is central to the differential
      regulation of LH and FSH and thus ovarian follicle development, the correct
      selection of a single dominant follicle for ovulation, the LH surge and the
      luteal phase.

PMID- 29171354
TI  - Haematology and coagulation profiles in cats with congenital portosystemic
      shunts.
AB  - Objectives The objectives of this study were, first, to report the haematological
      parameters and coagulation times for cats with a congenital portosystemic shunt
      (CPSS) and the influence of surgical shunt attenuation on these parameters; and,
      second, to identify any association between prolongation in coagulation profiles
      and incidence of perioperative haemorrhage. Methods This was a retrospective
      clinical study using client-owned cats with a CPSS. Signalment, shunt type (extra
      or intrahepatic), degree of shunt attenuation (complete or partial),
      haematological parameters, prothrombin time (PT) and activated partial
      thromboplastin time (aPTT) test results, and occurrence of any perioperative
      clinical bleeding complications were recorded for cats undergoing surgical
      treatment of a CPSS at the Royal Veterinary College, UK, between 1994 and 2011.
      Results Forty-two cats were included. Thirty-six (85.7%) had an extrahepatic CPSS
      and six (14.3%) had an intrahepatic CPSS. Preoperatively, mean cell volume (MCV)
      and mean cell haemoglobin (MCH) were below the reference interval (RI) in 32
      (76.2%) and 31 (73.8%) cats, respectively. Red blood cell count and mean cell
      haemoglobin concentration (MCHC) were above the RI in 10 (23.8%) and eight
      (19.1%) cats, respectively. Postoperatively, there were significant increases in
      haematocrit ( P = 0.044), MCV ( P = 0.008) and MCH ( P = 0.002). Despite the
      significant increase in MCV postoperatively, the median MCV postoperatively was
      below the RI, indicating persistence of microcytosis. Preoperatively, PT was
      above the upper RI in 14 cats (87.5%), and aPTT was above the upper RI in 11 cats
      (68.8%). No cat demonstrated a perioperative clinical bleeding complication.
      Conclusions and relevance Cats with a CPSS are likely to present with a
      microcytosis, but rarely present with anaemia, leukocytosis or thrombocytopenia.
      Surgical attenuation of the CPSS results in a significant increase in the HCT and
      MCV. Coagulation profiles in cats with a CPSS are likely to be prolonged,
      irrespective of shunt type, but do not appear to be associated with an increased
      risk of clinical bleeding.

PMID- 29171355
TI  - Overweight adult cats have significantly lower voluntary physical activity than
      adult lean cats.
AB  - Objectives The objectives of the current pilot study were to evaluate whether
      body condition score (BCS) and body weight are significantly related to physical
      activity counts, and to evaluate potential interaction between BCS and voluntary
      physical activity measured over a 14 day period. Methods Ten (five lean, five
      overweight), neutered, adult American Shorthair cats were selected for this study
      (median age 4 +/- 0.5 years). Cats with a BCS of ?3.0 were considered lean,
      whereas cats with a BCS >3.0 were considered overweight, using a 5-point scale.
      Cats were housed in a free-living environment with indoor/outdoor access and were
      individually fed once daily a commercially available dry extruded diet and
      allowed 1 h to eat. Voluntary physical activity was measured consecutively for 14
      days using the Actical Activity Monitors that were worn parallel to the ribs and
      attached via a harness. Results Lean cats had a greater mean total daily
      voluntary physical activity ( P = 0.0059), and a greater voluntary physical
      activity during light ( P = 0.0023) and dark ( P = 0.0446) periods, with
      overweight cats having 60% of the physical activity of lean cats. Lean cats were
      more active before feeding and during animal care procedures. These data suggest
      that lean cats have a greater anticipatory physical activity prior to feeding and
      are more eager to have social interaction with humans than overweight cats. A
      significant interaction was observed between day of physical activity measurement
      and BCS for total daily voluntary physical activity ( P = 0.0133) and activity
      during the light period ( P = 0.0016) where lean cats were consistently more
      active than overweight cats. In general, cats were more active during weekdays vs
      weekends. Conclusions and relevance The results of this study suggest that
      overweight cats are less active than lean cats and that voluntary physical
      activity level appears to be influenced by social interaction with humans.

PMID- 29171357
TI  - Parents' perceptions of children's executive functions across different cities.
AB  - Culture is thought to strongly influence the development of executive functions
      (EF), such that ethnic groups with similar cultural origins are generally assumed
      to exhibit comparable levels of EF performance. However, other characteristics,
      such as urbanization and Westernization, may also affect EF performance in
      societies comprising different ethnic groups, even if the ethnic groups share a
      similar cultural origin. The present study aimed to compare the perceptions of
      parents in three cities [China-Shenzhen (ZH group), China-Hong Kong (HK group),
      and Singapore (SG group)] regarding the EF performances of their children, all of
      whom share the same genetic and cultural (i.e., Chinese) origin. The study
      recruited 95 children aged 5-6 years (ZH group = 32; HK group = 32; SG group =
      31). Their parents were invited to complete the Behavior Rating Inventory of
      Executive Function (BRIEF). The ZH group had significantly lower BRIEF scores
      compared to both the HK and SG groups. However, the BRIEF scores of the HK and SG
      groups only differed significantly in terms of the Organization of Materials
      domain. The results suggest city-related differences in parents' perceptions of
      their children's EF performances, despite their similar genetic and cultural
      backgrounds. We additionally discuss further interpretations of our results and
      the limitations of this study.

PMID- 29171356
TI  - Antifatigue properties of tanshinone IIA in mice subjected to the forced swimming
      test.
AB  - CONTEXT: Tanshinone IIA (Tan IIA) is a constituent of Danshen Salvia miltiorrhiza
      Bunge (Lamiaceae); however, its antifatigue activity remains unclear. OBJECTIVE:
      To study the antifatigue properties of Tan IIA and its underlying mechanisms.
      MATERIALS AND METHODS: In program I, three mouse groups were separately subjected
      to three gavages with 0, 1 and 6 mg/kg Tan IIA and forced swimming test (FST)
      weekly for 8 weeks; in program II, one gavage with 0, 2 and 10 mg/kg Tan IIA was
      administered plus FST weekly for 4 weeks. Serum glucose, lactate, superoxide
      dismutase (SOD), malondialdehyde (MDA) and blood urea nitrogen (BUN) were
      determined after final FST. RESULTS: Tan IIA significantly prolonged swimming
      durations in program I but not in program II. Swimming times were 3208 +/- 1054
      and 2443 +/- 1054 s for the 1 and 6 mg/kg treatments and 856 +/- 292 s for the
      vehicle control. The two doses significantly reduced serum glucose levels (40.3
      +/- 8.5 and 60.0 1 +/- 11.8 mg/kg) and lactate levels (61.3 +/- 27.5 and 68.8 +/-
      8.5 mg/kg) in treated mice compared with those in control mice (137.5 +/- 38.6
      mg/kg and 122.7 +/- 18.2 mg/kg, respectively). However, no significant
      differences were observed regarding SOD, MDA or BUN levels. DISCUSSION AND
      CONCLUSIONS: Tan IIA has antifatigue activity and is associated with reductions
      in serum glucose and lactate levels. Further studies should assess muscle
      hypertrophy and efficient aerobic glycolysis caused by Tan IIA. Tan IIA has
      potential as a pharmacological agent for fatigue resistance.

PMID- 29171358
TI  - The comparative pharmacokinetics of physical manipulation by crushing of
      Xtampza(r) ER compared with OxyContin(r).
AB  - AIM: To further characterize the pharmacokinetics of Xtampza(r) ER. SUBJECTS &
      METHODS: This was an open-label, randomized, active-controlled, five-treatment,
      five-period, naltrexone-blocked, cross-over study. Healthy subjects received five
      equivalent oxycodone doses: Xtampza ER (intact or crushed), OxyContin(r) (intact
      or crushed) or immediate-release (IR) oxycodone (crushed). Blood samples were
      collected to assess oxycodone concentrations. RESULTS: Crushed and intact Xtampza
      ER resulted in lower peak plasma concentrations compared with crushed oxycodone
      IR; crushed and intact Xtampza ER were bioequivalent. Crushed OxyContin exhibited
      a rapid increase in plasma oxycodone and was bioequivalent to crushed oxycodone
      IR. CONCLUSION: This second pharmacokinetic study demonstrated that Xtampza ER
      maintains its ER properties after crushing, unlike OxyContin, which failed to
      retain its ER properties after crushing. ANZCTR registration number:
      ACTRN12614000613606.

PMID- 29171359
TI  - Effects of alteplase for acute stroke according to criteria defining the European
      Union and United States marketing authorizations: Individual-patient-data meta
      analysis of randomized trials.
AB  - Background The recommended maximum age and time window for intravenous alteplase
      treatment of acute ischemic stroke differs between the Europe Union and United
      States. Aims We compared the effects of alteplase in cohorts defined by the
      current Europe Union or United States marketing approval labels, and by
      hypothetical revisions of the labels that would remove the Europe Union upper age
      limit or extend the United States treatment time window to 4.5 h. Methods We
      assessed outcomes in an individual-patient-data meta-analysis of eight randomized
      trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic
      stroke. Outcomes included: excellent outcome (modified Rankin score 0-1) at 3-6
      months, the distribution of modified Rankin score, symptomatic intracerebral
      hemorrhage, and 90-day mortality. Results Alteplase increased the odds of
      modified Rankin score 0-1 among 2449/6136 (40%) patients who met the current
      European Union label and 3491 (57%) patients who met the age-revised label (odds
      ratio 1.42, 95% CI 1.21-1.68 and 1.43, 1.23-1.65, respectively), but not in those
      outside the age-revised label (1.06, 0.90-1.26). By 90 days, there was no
      increased mortality in the current and age-revised cohorts (hazard ratios 0.98,
      95% CI 0.76-1.25 and 1.01, 0.86-1.19, respectively) but mortality remained higher
      outside the age-revised label (1.19, 0.99-1.42). Similarly, alteplase increased
      the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the
      current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio
      1.55, 1.19-2.01 and 1.37, 1.17-1.59, respectively), but not for those outside the
      4.5-h revised approval (1.14, 0.97-1.34). By 90 days, no increased mortality
      remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99,
      0.77-1.26 and 1.02, 0.87-1.20, respectively) but mortality remained higher
      outside the 4.5-h revised approval (1.17, 0.98-1.41). Conclusions An age-revised
      European Union label or 4.5-h-revised United States label would each increase the
      number of patients deriving net benefit from alteplase by 90 days after acute
      ischemic stroke, without excess mortality.

PMID- 29171360
TI  - Canadian stroke best practice consensus statement: Secondary stroke prevention
      during pregnancy.
AB  - The Canadian Stroke Best Practice Consensus Statement: Secondary Stroke
      Prevention during Pregnancy, is the first of a two-part series devoted to stroke
      in pregnancy. This document focuses on unique aspects of secondary stroke
      prevention in a woman with a prior history of stroke or transient ischemic attack
      who is, or is planning to become, pregnant. Although stroke is relatively rare in
      this cohort, several aspects of pregnancy can increase stroke risk during or
      immediately after pregnancy. The rationale for the development of this consensus
      statement is based on the premise that stroke in this group requires a
      specifically-tailored management approach. No other broad-based, stroke-specific
      guidelines or consensus statements exist currently. Underpinning the development
      of this document was the concept that maternal health is vital for fetal
      wellbeing; therefore, management decisions should be based on the confluence of
      two clinical considerations: (a) decisions that would be made if the patient was
      not pregnant and (b) decisions that would be made if the patient had not had a
      stroke. While empirical research in this area is limited, this consensus document
      is based on the best available literature and guided by expert consensus. Issues
      addressed in this document include general management considerations for
      secondary stroke prevention, the use of antithrombotics, blood pressure
      management, lipid management, diabetes care, and management for specific ischemic
      stroke etiologies in pregnancy. The focus is on maternal and fetal health while
      minimizing risks of a recurrent stroke, through counseling, monitoring, and the
      safety of select pharmacotherapy. These statements are appropriate for health
      care professionals across all disciplines.

PMID- 29171361
TI  - Canadian stroke best practice recommendations: Secondary prevention of stroke,
      sixth edition practice guidelines, update 2017.
AB  - The 2017 update of The Canadian Stroke Best Practice Recommendations for the
      Secondary Prevention of Stroke is a collection of current evidence-based
      recommendations intended for use by clinicians across a wide range of settings.
      The goal is to provide guidance for the prevention of ischemic stroke recurrence
      through the identification and management of modifiable vascular risk factors.
      Recommendations include those related to diagnostic testing, diet and lifestyle,
      smoking, hypertension, hyperlipidemia, diabetes, antiplatelet and anticoagulant
      therapies, carotid artery disease, atrial fibrillation, and other cardiac
      conditions. Notable changes in this sixth edition include the development of core
      elements for delivering secondary stroke prevention services, the addition of a
      section on cervical artery dissection, new recommendations regarding the
      management of patent foramen ovale, and the removal of the recommendations on
      management of sleep apnea. The Canadian Stroke Best Practice Recommendations
      include a range of supporting materials such as implementation resources to
      facilitate the adoption of evidence to practice, and related performance measures
      to enable monitoring of uptake and effectiveness of the recommendations. The
      guidelines further emphasize the need for a systems approach to stroke care,
      involving an interprofessional team, with access to specialists regardless of
      patient location, and the need to overcome geographic barriers to ensure equity
      in access within a universal health care system.

PMID- 29171362
TI  - Complications of endovascular treatment for acute ischemic stroke: Prevention and
      management.
AB  - Endovascular mechanical thrombectomy (MT) for the treatment of acute stroke due
      to large vessel occlusion has evolved significantly with the publication of
      multiple positive thrombectomy trials. MT is now a recommended treatment for
      acute ischemic stroke. Mechanical thrombectomy is associated with a number of
      intra-procedural or post-operative complications, which need to be minimized and
      effectively managed to maximize the benefits of thrombectomy. Procedural
      complications include: access-site problems (vessel/nerve injury, access-site
      hematoma and groin infection); device-related complications (vasospasm, arterial
      perforation and dissection, device detachment/misplacement); symptomatic
      intracerebral hemorrhage; subarachnoid hemorrhage; embolization to new or target
      vessel territory. Other complications include: anesthetic/contrast-related, post
      operative hemorrhage, extra-cranial hemorrhage and pseudoaneurysm. Some
      complications are life-threatening and many lead to increased length of stay in
      intensive care and stroke units. Complications increase costs and delay the
      commencement of rehabilitation. Some may be preventable; the impact of others can
      be minimized with early detection and appropriate management. Both
      neurointerventionists and stroke specialists need to be aware of the risk
      factors, strategies for prevention, and management of these complications. With
      the increasing use of mechanical thrombectomy for the treatment of acute ischemic
      stroke, incidence and outcome of complications will need to be carefully
      monitored by stroke teams. In this narrative review, we examine the frequency of
      complications of MT in the treatment of acute ischemic stroke with an emphasis on
      periprocedural complications. Overall, from recent randomized controlled trials,
      the risk of complications with sequelae for patient from mechanical thrombectomy
      is ~15%. We discuss the management of complications and identify areas with
      limited evidence, which need further research. Search strategy and selection
      criteria Relevant evidence was found by searches of Medline and Cochrane Library,
      reference list, cross-referencing and main journal content pages. Search terms
      included "brain ischemia", "acute ischemic stroke", "cerebral infarction" AND
      "mechanical thrombectomy", "endovascular therapy", "endovascular treatment",
      "endovascular embolectomy", "intra-arterial" AND "randomized controlled trial",
      "non-randomised trials", "observational studies" AND "complications", "procedural
      complications", "peri-procedural complications", "device-related complications",
      "management", "treatment", "outcome". The search included only human studies, and
      was limited to studies published in English between January 2014 and November
      2016. The final reference list was selected on the basis of relevance to the
      topics covered in the Review. Guidelines for management of acute ischaemic stroke
      by the American Heart Association, the European Stroke Organisation, multi
      disciplinary guidelines and the National Institute for Health and Care Excellence
      (NICE) were also reviewed.

PMID- 29171363
TI  - Professor Wieslaw Nowinski: 25 years of contribution to the development of
      digital brain atlases.

PMID- 29171364
TI  - Endovascular embolization of branch-incorporated cerebral aneurysms.
AB  - Objectives The aim of this study was to examine the feasibility, technique, and
      clinical and angiographic outcomes of endovascular coiling to treat a cerebral
      aneurysm with a branch incorporated into the aneurysmal wall. Methods From 2012
      to 2016, 25 patients with 26 cerebral aneurysms having a branch incorporated into
      the aneurysm (9 unruptured, 17 ruptured) were treated to prevent rupture or re
      bleeding from the sac while preserving the incorporated branch by using single
      catheter ( n = 18), balloon-remodeling ( n = 4), stent-assisted coiling ( n = 3),
      or double-catheter ( n = 1) techniques. Results Endovascular coiling was
      conducted in 26 procedures without angiographic occlusion of the incorporated
      branch. Post-embolization angiography revealed near-complete occlusion ( n = 8;
      30.7%), neck remnant ( n = 13; 50%), and incomplete occlusion ( n = 5; 19.3%)
      aneurysms. Thromboembolisms were observed in four (15.4%) patients during or
      after the procedure. A procedure-related neurological deficit was observed in one
      (3.8%) patient. When patients with a preictal modified Rankin Scale (mRS) score
      of 3 presenting with grade 5 subarachnoid hemorrhage were excluded, all patients
      had favorable outcomes (mRS 0-2). Six (23.1%) recurrent aneurysms were observed
      during follow-up, five of which were treated endovascularly at 5-22 months
      without complication. The location of an aneurysm at the ICA-posterior
      communicating artery associated with the dominant-type posterior communicating
      artery was significantly associated with recurrence ( p = 0.041). Conclusions
      Cerebral aneurysms with an incorporated branch were safely treated using
      conventional endovascular coiling. However, treatment durability was
      unsatisfactory, especially for dominant-type ICA-posterior communicating artery
      aneurysms.

PMID- 29171365
TI  - [Distal femur fracture in a woman with a lower limb prosthesis.]
AB  - BACKGROUND: People who use a lower limb prosthesis can fracture their distal
      femur after a trivial fall; however, this kind of fracture is uncommon. CASE
      DESCRIPTION: A 53-year-old woman with a trans-tibial prosthesis fell in her
      kitchen. She felt pain just above the socket of the prosthesis, was unable to get
      up and her knee and leg were swollen. Radiographic imaging showed a distal femur
      fracture, for which she received a non-operative treatment with a stump cast. In
      consultation with the rehabilitation physician she received a conventional lower
      limb prosthesis after consolidation of the fracture. She mobilised adequately and
      was able to resume her activities at home and at work. CONCLUSION: Distal femur
      fractures in patients with a lower limb prosthesis can be recognised through pain
      just above the socket of the prosthesis. Conservative treatment, including the
      use of a stump cast, followed by mobilisation with an adapted prosthesis under
      supervision of a rehabilitation physician often results in a good outcome in
      terms of functionality.

PMID- 29171366
TI  - [Palmar and axillary hyperhidrosis in children: endoscopic thoracic sympathectomy
      using clips for an underestimated problem].
AB  - BACKGROUND: Palmar and axillary hyperhidrosis are defined as perspiration
      exceeding the body's 'normal' physiological need for thermal regulation. This
      condition affects about 1% of adolescents and children and may lead to
      psychosocial problems and poor school performance. CASE DESCRIPTION: We carried
      out an endoscopic thoracic sympathectomy (ETS) with clips in a 14-year-old girl
      and a 16-year-old girl who suffered from debilitating palmar and axillary
      hyperhidrosis. They were able to quickly resume their general daily activities
      and both were free of symptoms during an outpatient visit after 6 weeks.
      CONCLUSION: ETS using clips is a safe, relatively simple and effective technique,
      which may provide a permanent solution. ETS can be an option in case of therapy
      resistant debilitating hyperhidrosis. This surgical procedure should be carefully
      considered, possible causes should be excluded and ETS should not be offered as
      the first treatment option for children.

PMID- 29171367
TI  - [Unexpected metal in the pelvis].
AB  - A 69-year-old woman with right-sided flank pain, probably based on a
      ureteropelvic junction obstruction, underwent JJ-catheter placement under
      fluoroscopic guidance. X-ray showed an appendix filled with shot pellets. This
      phenomenon has been described earlier in Eskimo hunters, who were known to
      accidently swallow shot pellets lodged in hunted animals. Shot pellet
      accumulation can result in appendicitis perforata or lead poisoning.

PMID- 29171368
TI  - [Trisomy 18: how lethal is 'lethal'?]
AB  - Should active treatment be available for children with trisomy 18? In the
      Netherlands, trisomy 18 is described as a lethal condition leading to death
      during or immediately after birth. The Dutch course of action for trisomy 18 is
      termination of pregnancy, almost without exception, or passive treatment without
      medical interventions. But that approach might be outdated. We present a case
      that inspired physicians and parents to rethink the perception of trisomy 18.

PMID- 29171369
TI  - [Can sick leave be predicted in patients with non-traumatic arm, neck and/or
      shoulder complaints?]
AB  - OBJECTIVES: Impediments due to complaints of non-traumatic arm, neck and/or
      shoulder (CANS) during work often leads to consultation in primary care. This
      study examines the occurrence of sick leave among workers with new CANS, and
      evaluates sick leave trajectories and their characteristics. METHODS: This
      prospective 2-year cohort study included workers with a new CANS presenting in
      general practice. Participants filled out postal questionnaires on sick leave at
      6-monthly intervals. Latent class growth mixture modelling was used to identify
      distinct trajectories of sick leave. Multinomial regression analyses identified
      characteristics of the subgroups. RESULTS: During follow-up, of the 533
      participants 190 reported at least one episode of sick leave due to CANS. Three
      sick leave trajectories were distinguished: (a) 'low risk' trajectory (n = 366),
      with a constant low probability over time; (b) 'intermediate risk' trajectory,
      with a high probability at first consultation followed by a steep decrease in
      probability of sick leave (n = 122); (c) 'high risk' trajectory (n = 45), with a
      constant high probability of sick leave. Compared to the 'low-risk' trajectory,
      the other trajectories were characterised by more functional limitations, less
      specific diagnoses, more work-related symptoms and low coworker support. Specific
      for the 'high-risk' subgroup were more recurrent symptoms, more musculoskeletal
      comorbidity, high score on somatisation and low score on job demands.
      CONCLUSIONS: Three trajectories of sick leave were distinguished, graded from
      favourable to unfavourable. Several complaint-related and work-related factors
      and somatisation contributed modestly to identify an unfavourable trajectory of
      sick leave when presenting in primary care with CANS.

PMID- 29171370
TI  - [Ocular involvement in Stevens-Johnson syndrome: treatment with amniotic membrane
      transplantation in the acute phase].
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are both part
      of a spectrum of serious mucocutaneous disorders, most often caused by drugs,
      with a high morbidity and mortality. In the acute stage, serious skin and
      mucocutaneous lesions with painful blistering, erosions and systemic involvement
      present the main focus of attention. The severity of skin manifestations in the
      acute stage, however, does not necessarily correlate with that of the mucosal
      lesions. Most feared are long-term sequelae, especially chronic eye involvement,
      which can be highly disabling. Here, we illustrate the importance of daily
      evaluation, early recognition and treatment of eye involvement in the acute stage
      of SJS/TEN, even when skin manifestations and/or initial eye involvement are
      relatively mild. Timely performed amniotic membrane transplantation in the acute
      stage can limit irreversible damage, caused by chronic inflammation, and
      therefore prevent cicatrisation at a later stage.

PMID- 29171371
TI  - [Safe medication administration in hospitals].
AB  - - Every day medication is administered to thousands of hospital inpatients, and
      medication administration errors can occur.- Interventions to reduce medication
      administration errors have been developed and tested; these include training,
      double-checking procedures, and technological solutions (such as smart infusion
      pumps and barcode-controlled drug administration).- Most of the studies that
      investigated these interventions were small, meaning it is unclear which
      intervention is the most effective. More research is needed to identify the best
      solutions.

PMID- 29171372
TI  - [Two pulmonary lesions on an X-ray of the chest].
AB  - We present an X-ray of a 89-year-old man, showing two solitary pulmonary lesions.
      Although malignancy was suspected, these lesions appeared to be intrafissural
      pleural effusions, caused by congestive heart failure. One week after treatment
      with furosemide, the pulmonary lesions had disappeared completely.

PMID- 29171373
TI  - [Is our treatment of well-differentiated thyroid cancer too aggressive?
      Hemithyroidectomy versus total thyroidectomy].
AB  - Recent literature shows that hemithyroidectomy is a safe alternative for total
      thyroidectomy in the treatment of patients with well-differentiated thyroid
      cancer up to 4 cm in diameter and a low risk of recurrence. According to criteria
      of the 2015 American Thyroid Association guidelines, more than 28% of patients
      with well-differentiated thyroid cancer of a Dutch cohort would be eligible for
      hemithyroidectomy instead of the total thyroidectomy they actually underwent.
      However, standardisation and high quality pre- and postoperative diagnostics are
      required for responsible implementation of this new guideline in Dutch
      healthcare.

PMID- 29171374
TI  - [From facial pain to toxic epidermal necrolysis: a rare complication of
      carbamazepine usage].
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare disease that is
      characterised by epidermal loss, often as a result of medication use -
      particularly sulfonamides and anti-epileptics. People of South-East Asian descent
      are at increased risk of developing TEN since they may carry the HLA-B*1502
      allele. CASE DESCRIPTION: A 61-year-old female of Indonesian descent developed
      TEN due to carbamazepine use, resulting in admission to the intensive care
      department of a specialised burn centre in the Netherlands. She was successfully
      treated with high-dose prednisone and local therapy for the skin disorder.
      CONCLUSION: The US Food and Drug Administration advises screening of patients of
      South-East Asian descent for HLA-B*1502 prior to initiation of treatment with TEN
      related medication. In the Netherlands, screening for this allele is currently
      not mandatory.

PMID- 29171375
TI  - [Spondylodiscitis as a rare manifestation of gout].
AB  - BACKGROUND: Spondylodiscitis is usually caused by microorganisms, but there are
      also non-infectious causes. CASE DESCRIPTION: We are describing an 84-year-old
      man with severe pain in the side and elevated inflammation parameters. MRI of the
      spinal column yielded a picture suggesting spondylodiscitis. Repeated peripheral
      cultures and culture of a vertebral biopsy did not yield a pathogen. Intravenous
      antibiotics had no effect on symptoms or inflammation parameters. When the
      physical examination was repeated, we found arthritis in the feet and tophi.
      Microscopic examination of a new vertebral biopsy found urate crystals. This
      meant we were dealing with spondylodiscitis as manifestation of gout. Treatment
      with colchicine was highly successful. CONCLUSION: Spinal column gout is unknown,
      but seems to occur with some regularity. This disease can be symptom-free but may
      also lead to myelopathy or spondylodiscitis. In case of spondylodiscitis without
      demonstrated pathogen in patients with gout or risk factors for this, the
      vertebral biopsy should be evaluated for urate crystals or a dual-energy CT
      should be considered.

PMID- 29171376
TI  - [Awareness during focal epileptic seizures].
AB  - Not all epileptic seizures are accompanied by loss of awareness. Focal aware
      seizures provide an opportunity to predict the location of the epileptic source
      in the brain. The impact of these seizures is often underestimated, especially if
      someone has previously had seizures with loss of awareness.

PMID- 29171377
TI  - [Off-label prescription of antipsychotics].
AB  - Antipsychotic medication is frequently prescribed for off-label use in
      individuals with intellectual disability and elderly persons, in particular to
      reduce challenging behaviour. However, clear evidence for effectiveness is scarce
      and long-term use of antipsychotics is associated with a wide range of serious
      side-effects, including movement disorders and metabolic syndrome. Therefore, off
      label use of antipsychotics in these populations has been widely debated.
      Nevertheless, non-pharmacological interventions alone are not always effective
      and a treatment attempt with an antipsychotic is sometimes inevitable. In this
      commentary, it is argued that clinicians should focus on the decision-making
      process in prescribing antipsychotics, rather than focus on discontinuation of
      these medications.

PMID- 29171378
TI  - [Safe administration of medicines: learning from our mistakes].
AB  - This issue of the Dutch Journal of Medicine (NTvG) features a review article by
      Van der Veen et al. on safe administration of medicines in hospitals. This topic
      is part of an increased focus on patient safety that started at the beginning of
      the 21st century, following publication of the renowned report 'To err is human'.
      Now, almost 20 years later, we are a little disappointed that there is still no
      set of interventions that can be implemented to guarantee safe administration of
      medicines in hospitals. Why ever not? In this commentary we discuss the main
      limitations of the interventions that have been studied, but also describe what
      we think can already be implemented without further research.

PMID- 29171388
TI  - Pyoderma gangrenosum developing over a skin ulcer due to arteriovenous
      malformation.

PMID- 29171379
TI  - CollAborative care for Screen-Positive EldeRs with major depression (CASPER
      plus): a multicentred randomised controlled trial of clinical effectiveness and
      cost-effectiveness.
AB  - BACKGROUND: Depression in older adults is common and is associated with poor
      quality of life, increased morbidity and early mortality, and increased health
      and social care use. Collaborative care, a low-intensity intervention for
      depression that is shown to be effective in working-age adults, has not yet been
      evaluated in older people with depression who are managed in UK primary care. The
      CollAborative care for Screen-Positive EldeRs (CASPER) plus trial fills the
      evidence gap identified by the most recent guidelines on depression management.
      OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of
      collaborative care for older adults with major depressive disorder in primary
      care. DESIGN: A pragmatic, multicentred, two-arm, parallel, individually
      randomised controlled trial with embedded qualitative study. Participants were
      automatically randomised by computer, by the York Trials Unit Randomisation
      Service, on a 1 : 1 basis using simple unstratified randomisation after informed
      consent and baseline measures were collected. Blinding was not possible. SETTING:
      Sixty-nine general practices in the north of England. PARTICIPANTS: A total of
      485 participants aged >= 65 years with major depressive disorder. INTERVENTIONS:
      A low-intensity intervention of collaborative care, including behavioural
      activation, delivered by a case manager for an average of six sessions over 7-8
      weeks, alongside usual general practitioner (GP) care. The control arm received
      only usual GP care. MAIN OUTCOME MEASURES: The primary outcome measure was
      Patient Health Questionnaire-9 items score at 4 months post randomisation.
      Secondary outcome measures included depression severity and caseness at 12 and 18
      months, the EuroQol-5 Dimensions, Short Form questionnaire-12 items, Patient
      Health Questionnaire-15 items, Generalised Anxiety Disorder-7 items, Connor
      Davidson Resilience Scale-2 items, a medication questionnaire, objective data and
      adverse events. Participants were followed up at 12 and 18 months. RESULTS: In
      total, 485 participants were randomised (collaborative care, n = 249; usual care,
      n = 236), with 390 participants (80%: collaborative care, 75%; usual care, 86%)
      followed up at 4 months, 358 participants (74%: collaborative care, 70%; usual
      care, 78%) followed up at 12 months and 344 participants (71%: collaborative
      care, 67%; usual care, 75%) followed up at 18 months. A total of 415 participants
      were included in primary analysis (collaborative care, n = 198; usual care, n =
      217), which revealed a statistically significant effect in favour of
      collaborative care at the primary end point at 4 months [8.98 vs. 10.90 score
      points, mean difference 1.92 score points, 95% confidence interval (CI) 0.85 to
      2.99 score points; p  < 0.001], equivalent to a standard effect size of 0.34.
      However, treatment differences were not maintained in the longer term (at 12
      months: 0.19 score points, 95% CI -0.92 to 1.29 score points; p = 0.741; at 18
      months: < 0.01 score points, 95% CI -1.12 to 1.12 score points; p = 0.997). The
      study recorded details of all serious adverse events (SAEs), which consisted of
      'unscheduled hospitalisation', 'other medically important condition' and 'death'.
      No SAEs were related to the intervention. Collaborative care showed a small but
      non-significant increase in quality-adjusted life-years (QALYs) over the 18-month
      period, with a higher cost. Overall, the mean cost per incremental QALY for
      collaborative care compared with usual care was L26,016; however, for
      participants attending six or more sessions, collaborative care appears to
      represent better value for money (L9876/QALY). LIMITATIONS: Study limitations are
      identified at different stages: design (blinding unfeasible, potential
      contamination), process (relatively low overall consent rate, differential
      attrition/retention rates) and analysis (no baseline health-care resource cost or
      secondary/social care data). CONCLUSION: Collaborative care was effective for
      older people with case-level depression across a range of outcomes in the short
      term though the reduction in depression severity was not maintained over the
      longer term of 12 or 18 months. Participants who received six or more sessions of
      collaborative care did benefit substantially more than those who received fewer
      treatment sessions but this difference was not statistically significant. FUTURE
      WORK RECOMMENDATIONS: Recommendations for future research include investigating
      the longer-term effect of the intervention. Depression is a recurrent disorder
      and it would be useful to assess its impact on relapse and the prevention of
      future case-level depression. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN45842879. 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. 67. See the NIHR
      Journals Library website for further project information.

PMID- 29171389
TI  - Dermoscopic characteristics of transient acantholytic dermatosis (Grover's
      disease).

PMID- 29171390
TI  - Trichophyton verrucosum: an atypical infection on the pubis.

PMID- 29171391
TI  - Clinical outcomes of primary cutaneous anaplastic large cell lymphoma: data from
      a single Japanese centre.

PMID- 29171392
TI  - Clinical assessment of skin phototypes: watch your words!
AB  - Fitzpatrick skin phototype classification is widely used to assess risk factors
      for skin cancers. This skin type evaluation is easy to use in clinical practice
      but is not always applied as initially described, nor practiced in a standardised
      way. This can have implications on the results of relevant dermato
      epidemiological studies. To demonstrate, in a large multinational setting, that
      the phrasing of questions on sun sensitivity can have a strong impact on the
      perception and reporting of skin phototype, as well as the importance of a
      standardised procedure for phototype assessment. Using data collected from 48,258
      screenees of the Euromelanoma campaign in six European countries from 2009 to
      2011, we analysed the impact of change in the question phrasing on phototype
      classification in each country. Changing the wording of a question to assess the
      phototype of a person also significantly influenced the classification of
      phototypes in different countries (p<0.001 for each country). The difference
      essentially corresponded to a shift towards a less sun-sensitive skin type when a
      shorter question that did not include skin colour description was used. The only
      exception was Portugal where phototype was not patient-assessed and
      classification shifted towards a more sun-sensitive phototype. Results were
      statistically significant and highly consistent, irrespective of gender. The
      phrasing of questions on skin type is important and substantially influences
      reporting. A standardized procedure to classify phototypes should be used in
      order to obtain comparable data between studies.

PMID- 29171393
TI  - Characterization of skin Th17 transcriptional profiles in psoriatic patients
      under adalimumab biotherapy.
AB  - In psoriasis, a specific cytokine network has been described to play a central
      role in the pathophysiology of the disease. Anti-cytokine therapeutic approaches
      have been largely developed and TNFalpha constitutes the main target. Adalimumab
      is a human anti-TNFalpha monoclonal antibody that has been reported to
      demonstrate clinical efficacy and safety, resulting in reversal of epidermal
      hyperplasia and cutaneous inflammation. We aimed to analyse changes in the skin
      inflammatory transcriptomic profile in psoriatic patients during adalimumab
      therapy. In addition, the circulating cytokine profile was analysed to define
      systemic inflammation. Eighteen patients with chronic plaque psoriasis were
      treated with adalimumab. After four and 16 weeks, clinical efficacy was assessed
      using PASI and DLQI, and skin mRNA profiles were determined and circulating
      cytokines quantified. We identified a rapid effect of adalimumab therapy on a
      large array of Th17 cytokines of the skin, which may account for the modification
      of keratinocyte expression profile and clinical response. In contrast, analysis
      of serum cytokine concentrations was uninformative, confirming the need for
      characterization of local cytokines in skin lesions. Finally, in non-responders,
      local cytokine expression was shown to be unchanged. We show that TNFalpha
      inhibition in psoriasis patients treated with adalimumab has a broad effect on
      the expression profile of cytokines and keratinocyte markers of skin
      inflammation, which may account for its clinical efficacy.

PMID- 29171394
TI  - Superficial epidermolytic ichthyosis concomitant with atopic dermatitis.

PMID- 29171395
TI  - Incidence and ten-year follow-up of primary cutaneous lymphomas: a single-centre
      cohort study.
AB  - BACKGROUND: Primary cutaneous lymphomas (PCLs) are a rare group of extranodal non
      Hodgkin lymphomas, and epidemiological data in Mediterranean countries are
      scarce. OBJECTIVE: To investigate the incidence and characteristics of PCL in a
      single tertiary referral centre in Italy. MATERIALS & METHODS: A total of 141 PCL
      patients, seen over a 10-year follow-up period, were investigated. RESULTS:
      Incidence rate of PCL was 0.8 cases/100,000 person years. T-cell lymphoma
      represented 78.7% of all cases, the majority being early mycosis fungoides (MF)
      (64%; median age: 66 years), followed by lymphomatoid papulosis (LyP) (19%;
      median: age 48 years), and others (median age: 72 years), including eight cases
      of anaplastic large CD30+ T-cell lymphoma, four CD4+ small-medium pleomorphic T
      cell lymphoproliferative disorder, four Sezary syndrome, one subcutaneous
      panniculitis-like T-cell lymphoma, one extranodal NK/T-cell lymphoma nasal-type,
      and one angioimmunoblastic T-cell lymphoma. B-cell lymphoma accounted for 21.3%
      of PCL, with 20 cases of cutaneous follicular centre B-cell (median age: 63
      years), four primary cutaneous marginal zone, three primary cutaneous diffuse
      large B-cell, and three leg-type lymphoma. Complete remission within the first
      year after diagnosis occurred in 70.4% of MF, 61.9% of LyP, 78.9% of other T-cell
      lymphoma, and 93.1% of B-cell lymphoma cases. Based on a Cox proportional hazard
      regression model, age, gender, stage, and lactate dehydrogenase and beta2
      microglobulin blood levels did not predict clinical remission of MF or LyP.
      CONCLUSIONS: The incidence and characteristics of PCL in Italy are similar to
      those in other European countries. PCLs may be diagnosed at very early stages
      with good prognosis.

PMID- 29171396
TI  - Sleep-related hypermotor epilepsy activated by rapid eye movement sleep.
AB  - Most sleep-related seizures occur during non-rapid eye movement (NREM) sleep,
      particularly during stage changes. Sleep-related hypermotor epilepsy (SHE) is a
      rare epileptic syndrome characterized by paroxysmal motor seizures, mainly
      arising from NREM sleep. Here, we report a patient with SHE who had seven
      seizures captured on video-EEG-polysomnography during REM sleep. Ictal semiology
      of this patient ranged from brief paroxysmal arousals to hypermotor seizures. On
      EEG-polysomnography, the spontaneous arousals were more frequent during REM than
      NREM sleep, with a considerably higher arousal index in REM sleep (20/hour).
      While the reason for seizures during REM sleep in this patient is unclear, we
      speculate that the threshold and mechanisms of arousal during different sleep
      stages may be related to the occurrence of seizures. [Published with video
      sequences on www.epilepticdisorders.com].

PMID- 29171397
TI  - Crossing the lines between epilepsy syndromes: a myoclonic epilepsy variant with
      prominent eyelid myoclonia and atonic components.
AB  - Accurate diagnosis of a distinct epilepsy syndrome is based on well-defined
      electroclinical features that differentiate separate nosological entities. In
      clinical practice, however, syndromes may overlap and cases may present with
      unusual manifestations posing a diagnostic challenge. This heterogeneity has been
      documented in several cases presenting with eyelid myoclonia with or without
      absences (EMA) diagnosed either as Jeavons syndrome (JS) variants or as genetic
      generalised epilepsies defined by the presence of this unique clinical entity.
      The hallmark of JS is the triad: (1) eyelid myoclonia with or without absences,
      (2) eye closure-induced paroxysms, and (3) photosensitivity. The presence of
      massive myoclonus, intellectual disability, or slowing of the EEG background are
      not typical features of the syndrome and may cause delay in making the correct
      diagnosis. Adding to the variability of clinical features, we describe two female
      paediatric patients with probable genetic epilepsy who presented with EMA but
      demonstrated clear atypical features, such as prominent myoclonic seizures,
      atonic components on video-EEG, and cognitive impairment. We also note the
      presence of interictal and ictal posterior discharges during eyelid myoclonia in
      one, supporting similar previous observations leading to consideration of EMA as
      an occipital cortex-initiated seizure activity. [Published with video sequences
      on www.epilepticdisorders.com].

PMID- 29171398
TI  - Primary cutaneous mucormycosis as a complication of erosive dermatitis: two
      cases.

PMID- 29171399
TI  - AFAST: an adult female acne treatment algorithm for daily clinical practice.

PMID- 29171400
TI  - Reactivity to anti-RNA polymerase III antibody and nailfold capillary changes in
      patient with generalized morphea combined with multiple autoimmune disorders.

PMID- 29171401
TI  - A case of peripheral T-cell lymphoma, not otherwise specified, with rapid
      progression to erythroderma.

PMID- 29171402
TI  - A short period of breastfeeding in infancy, excessive house cleaning, absence of
      older sibling, and passive smoking are related to more severe atopic dermatitis
      in children.
AB  - BACKGROUND: Atopic dermatitis (AD) is one of the most common, chronic or
      chronically relapsing inflammatory skin diseases that affect children. Multiple
      genetic and environmental factors appear to regulate the pathogenesis of AD.
      OBJECTIVES: Our aim was to investigate the possible association between family,
      social, dieting, atopic and environmental factors and the severity of AD
      evaluated by SCORAD scores in children. MATERIALS & METHODS: The study group
      included 100 children with AD who attended a paediatric dermatology outpatient
      clinic with a median age of 18.5 months. The diagnosis of AD was established on
      the basis of the clinical criteria according to the American Dermatology Society,
      while the SCORAD score was used to evaluate disease severity. RESULTS:
      Multivariate linear regression analysis disclosed that excessive cleanliness
      (p<0.001), RAST level greater than 0.7 KU/l (p<0.001), breastfeeding for less
      than two months (p = 0.001), and the absence of an older sibling (p = 0.049) were
      statistically significant independent determinants for high SCORAD scores.
      Multivariate logistic regression analysis showed that excessive cleanliness
      (p<0.001) was the strongest independent risk factor for severe AD (SCORAD>36)
      (aOR: 59.4; 95% CI: 10.9-322.6). RAST level greater than 0.7 KU/l (aOR: 7.9; 95%
      CI: 1.5-41.0; p = 0.014) and severe passive smoking (aOR: 4.6; 95% CI: 1.0-22.1;
      p = 0.050) also showed a significant independent, but clearly weaker, association
      with severe AD. CONCLUSIONS: A short duration of breastfeeding, absence of older
      siblings, parental passive smoking, food allergens along with aeroallergens, and
      excessive cleanliness should be considered as negative prognostic factors,
      leading to a higher SCORAD score in children with AD.

PMID- 29171403
TI  - Age-specific prevalence of psoriasis in an unselected sample of 25,956 Italian
      hospital inpatients: evidence for selective excess mortality after 70 years of
      age.

PMID- 29171404
TI  - Successful treatment of isoniazid-induced lichenoid drug eruption with acitretin.

PMID- 29171405
TI  - Seizure semiology of anti-LGI1 antibody encephalitis.
AB  - Limbic encephalitis associated with anti-LGI1 antibody (LGI1 encephalitis)
      presents with a variety of features, the most prominent of which include seizures
      and progressive disturbance of memory and behaviour. Although varied in
      semiology, recognition of the pattern of seizures in LGI1 encephalitis is
      important, as early diagnosis and definitive treatment may prevent subsequent
      development of cognitive impairment. We present a patient with LGI1 encephalitis
      and "faciobrachial dystonic seizures-plus", which began as classic faciobrachial
      dystonic seizures and progressed to focal seizures with impaired awareness,
      dacrystic/gelastic-like outbursts, ictal speech, manual automatisms, and
      autonomic signs (tachycardia). Recognition of the broad range of seizure types
      associated with LGI1 encephalitis is crucial for early diagnosis and definitive
      treatment. [Published with video sequence on www.epilepticdisorders.com].

PMID- 29171406
TI  - Dermoscopic features of cutaneous Langerhans cell histiocytosis.

PMID- 29171407
TI  - Vitamin D levels in a cohort of Portuguese melanoma patients relate to time of
      follow-up from diagnosis, sun-exposure behaviour, and use of photoprotection.

PMID- 29171408
TI  - Melanoma and tattoos: a case report and review of the literature.
AB  - BACKGROUND: Malignant melanoma cases arising in tattoos have been increasingly
      described, however, there is no clear relationship between this practice and the
      development of cutaneous malignancies. OBJECTIVES: We report a new case of
      melanoma in a dark-blue tattoo and we review all cases of melanoma reported in
      the medical literature from 1938 to date. MATERIALS & METHODS: Pubmed and Google
      Scholar were searched using the terms "melanoma tattoo", "tattoo skin tumour" and
      "ink melanoma". RESULTS: In most cases, the melanoma occurred on dark blue
      (10/30), black (8/30), or blue ink (3/30). The Breslow thickness at diagnosis was
      <=1 mm in 13/30, 1-2 mm in 3/30, 2-4 mm in 2/30, >4 mm in 5/30, and Clark II in
      2/30 (not available in 5/30). CONCLUSIONS: Both the incidence of melanoma and the
      number of tattoos have been increasing in recent years, but a possible
      carcinogenic effect of tattoos remains unproven. The spread of this decorative
      custom will make observation of melanoma in tattoos more frequent in
      dermatological practice, therefore these cases should be reported in national
      skin cancer registries.

PMID- 29171409
TI  - A case of malignant melanoma that developed multiple metastases after switching
      from interferon-beta to pegylated interferon-alpha-2b as adjuvant therapy.

PMID- 29171410
TI  - Correction: Structural and functional connectivity in traumatic brain injury.

PMID- 29171411
TI  - Beta secretase activity in peripheral nerve regeneration.
AB  - While the peripheral nervous system has the capacity to regenerate following a
      nerve injury, it is often at a slow rate and results in unsatisfactory recovery,
      leaving patients with reduced function. Many regeneration associated genes have
      been identified over the years, which may shed some insight into how we can
      manipulate this intrinsic regenerative ability to enhance repair following
      peripheral nerve injuries. Our lab has identified the membrane bound protease
      beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), or beta secretase,
      as a potential negative regulator of peripheral nerve regeneration. When beta
      secretase activity levels are abolished via a null mutation in mice, peripheral
      regeneration is enhanced following a sciatic nerve crush injury. Conversely, when
      activity levels are greatly increased by overexpressing beta secretase in mice,
      nerve regeneration and functional recovery are impaired after a sciatic nerve
      crush injury. In addition to our work, many substrates of beta secretase have
      been found to be involved in regulating neurite outgrowth and some have even been
      identified as regeneration associated genes. In this review, we set out to
      discuss BACE1 and its substrates with respect to axonal regeneration and
      speculate on the possibility of utilizing BACE1 inhibitors to enhance
      regeneration following acute nerve injury and potential uses in peripheral
      neuropathies.

PMID- 29171413
TI  - On the road towards the global analysis of human synapses.
AB  - Synapses are essential units for the flow of information in the brain. Over the
      last 70 years, synapses have been widely studied in multiple animal models
      including worms, fruit flies, and rodents. In comparison, the study of human
      synapses has evolved significantly slower, mainly because of technical
      limitations. However, three novel methods allowing the analysis of molecular,
      morphological, and functional properties of human synapses may expand our
      knowledge of the human brain. Here, we briefly describe these methods, and
      evaluate how the information provided by each unique approach may contribute to
      the functional and anatomical analysis of the synaptic component of human brain
      circuitries. In particular, using tissue from cryopreserved human brains,
      synaptic plasticity can be studied in isolated synaptosomes by fluorescence
      analysis of single-synapse long-term potentiation (FASS-LTP), and subpopulations
      of synapses can be thoroughly assessed in the ribbons of brain tissue by array
      tomography (AT). Currently, it is also possible to quantify synaptic density in
      the living human brain by positron emission tomography (PET), using a novel
      synaptic radio-ligand. Overall, data provided by FASS-LTP, AT, and PET may
      significantly contribute to the global understanding of synaptic structure and
      function in both healthy and diseased human brains, thus directly impacting
      translational research.

PMID- 29171414
TI  - Non-invasive electrical brain stimulation: from acute to late-stage treatment of
      central nervous system damage.
AB  - Non-invasive brain current stimulation (NIBS) is a promising and versatile tool
      for inducing neuroplasticity, protection and functional rehabilitation of damaged
      neuronal systems. It is technically simple, requires no surgery, and has
      significant beneficial effects. However, there are various technical approaches
      for NIBS which influence neuronal networks in significantly different ways.
      Transcranial direct current stimulation (tDCS), alternating current stimulation
      (ACS) and repetitive transcranial magnetic stimulation (rTMS) all have been
      applied to modulate brain activity in animal experiments under normal and
      pathological conditions. Also clinical trials have shown that tDCS, rTMS and ACS
      induce significant behavioural effects and can - depending on the parameters
      chosen - enhance or decrease brain excitability and influence performance and
      learning as well as rehabilitation and protective mechanisms. The diverse
      phaenomena and partially opposing effects of NIBS are not yet fully understood
      and mechanisms of action need to be explored further in order to select
      appropriate parameters for a given task, such as current type and strength,
      timing, distribution of current densities and electrode position. In this review,
      we will discuss the various parameters which need to be considered when designing
      a NIBS protocol and will put them into context with the envisaged applications in
      experimental neurobiology and medicine such as vision restoration, motor
      rehabilitation and cognitive enhancement.

PMID- 29171415
TI  - Using 3D bioprinting to produce mini-brain.

PMID- 29171416
TI  - Matrix bound vesicles and miRNA cargoes are bioactive factors within
      extracellular matrix bioscaffolds.

PMID- 29171417
TI  - Collagen 1 signaling at the central nervous system injury site and astrogliosis.

PMID- 29171412
TI  - Embracing oligodendrocyte diversity in the context of perinatal injury.
AB  - Emerging evidence is fueling a new appreciation of oligodendrocyte diversity that
      is overturning the traditional view that oligodendrocytes are a homogenous cell
      population. Oligodendrocytes of distinct origins, maturational stages, and
      regional locations may differ in their functional capacity or susceptibility to
      injury. One of the most unique qualities of the oligodendrocyte is its ability to
      produce myelin. Myelin abnormalities have been ascribed to a remarkable array of
      perinatal brain injuries, with concomitant oligodendrocyte dysregulation. Within
      this review, we discuss new insights into the diversity of the oligodendrocyte
      lineage and highlight their relevance in paradigms of perinatal brain injury.
      Future therapeutic development will be informed by comprehensive knowledge of
      oligodendrocyte pathophysiology that considers the particular facets of
      heterogeneity that this lineage exhibits.

PMID- 29171418
TI  - Can we treat neurodegenerative diseases by preventing an age-related decline in
      microRNA expression?

PMID- 29171419
TI  - Soluble interleukin 23 receptor gene therapy with adeno-associated vectors for
      the treatment of multiple sclerosis.

PMID- 29171420
TI  - Human induced pluripotent stem cell based in vitro models of the blood-brain
      barrier: the future standard?

PMID- 29171421
TI  - Mitochondrial malfunction in vanishing white matter disease: a disease of the
      cytosolic translation machinery.

PMID- 29171422
TI  - Electrical stimulation of cortical neurons promotes oligodendrocyte development
      and remyelination in the injured spinal cord.

PMID- 29171423
TI  - Neuregulin-1: a novel regulator of glial response in spinal cord injury.

PMID- 29171424
TI  - Interactions of primary insult biomechanics and secondary cascades in spinal cord
      injury: implications for therapy.

PMID- 29171425
TI  - Mechanisms of retinal neuroprotection of calcium dobesilate: therapeutic
      implications.

PMID- 29171426
TI  - Pharmacological induced target temperature management after cardiac arrest: the
      capsaicinoids.

PMID- 29171427
TI  - Baicalin protects neonatal rat brains against hypoxic-ischemic injury by
      upregulating glutamate transporter 1 via the phosphoinositide 3-kinase/protein
      kinase B signaling pathway.
AB  - Baicalin is a flavonoid compound extracted from Scutellaria baicalensis root.
      Recent evidence indicates that baicalin is neuroprotective in models of ischemic
      stroke. Here, we investigate the neuroprotective effect of baicalin in a neonatal
      rat model of hypoxic-ischemic encephalopathy. Seven-day-old pups underwent left
      common carotid artery ligation followed by hypoxia (8% oxygen at 37 degrees C)
      for 2 hours, before being injected with baicalin (120 mg/kg intraperitoneally)
      and examined 24 hours later. Baicalin effectively reduced cerebral infarct volume
      and neuronal loss, inhibited apoptosis, and upregulated the expression of p-Akt
      and glutamate transporter 1. Intracerebroventricular injection of the
      phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) inhibitor LY294002 30
      minutes before injury blocked the effect of baicalin on p-Akt and glutamate
      transporter 1, and weakened the associated neuroprotective effect. Our findings
      provide the first evidence, to our knowledge that baicalin can protect neonatal
      rat brains against hypoxic-ischemic injury by upregulating glutamate transporter
      1 via the PI3K/Akt signaling pathway.

PMID- 29171428
TI  - The role of glycogen synthase kinase 3 beta in brain injury induced by myocardial
      ischemia/reperfusion injury in a rat model of diabetes mellitus.
AB  - Myocardial ischemia/reperfusion injury can lead to severe brain injury. Glycogen
      synthase kinase 3 beta is known to be involved in myo-cardial
      ischemia/reperfusion injury and diabetes mellitus. However, the precise role of
      glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced
      brain injury is unclear. In this study, we observed the effects of glycogen
      synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion
      injury in diabetic rats. Rat models of diabetes mellitus were generated via
      intraperitoneal injection of streptozotocin. Models of myocardial
      ischemia/reperfusion injury were generated by occluding the anterior descending
      branch of the left coronary artery. Post-conditioning comprised three cycles of
      ischemia/reperfusion. Immunohistochemical staining and western blot assays
      demonstrated that after 48 hours of reperfusion, the structure of the brain was
      seriously damaged in the experimental rats compared with normal controls.
      Expression of Bax, interleukin-6, interleukin-8, terminal deoxynucleotidyl
      transferase dUTP nick end labeling, and cleaved caspase-3 in the brain was
      significantly increased, while expression of Bcl-2, interleukin-10, and phospho
      glycogen synthase kinase 3 beta was decreased. Diabetes mellitus can aggravate
      inflammatory reactions and apoptosis. Ischemic post-conditioning with glycogen
      synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these
      changes. Our results showed that myocardial ischemic post-conditioning attenuated
      myocardial ischemia/reperfusion injury-induced brain injury by activating glyco
      gen synthase kinase 3 beta. According to these results, glycogen synthase kinase
      3 beta appears to be an important factor in brain injury induced by myocardial
      ischemia/reperfusion injury.

PMID- 29171429
TI  - Age-related connectivity differences between attention deficit and hyperactivity
      disorder patients and typically developing subjects: a resting-state functional
      MRI study.
AB  - Attention deficit and hyperactivity disorder (ADHD) is a disorder characterized
      by behavioral symptoms including hyperactivity/impulsivity among children,
      adolescents, and adults. These ADHD related symptoms are influenced by the
      complex interaction of brain networks which were under explored. We explored age
      related brain network differences between ADHD patients and typically developing
      (TD) subjects using resting state fMRI (rs-fMRI) for three age groups of
      children, adolescents, and adults. We collected rs-fMRI data from 184 individuals
      (27 ADHD children and 31 TD children; 32 ADHD adolescents and 32 TD adolescents;
      and 31 ADHD adults and 31 TD adults). The Brainnetome Atlas was used to define
      nodes in the network analysis. We compared three age groups of ADHD and TD
      subjects to identify the distinct regions that could explain age-related brain
      network differences based on degree centrality, a well-known measure of nodal
      centrality. The left middle temporal gyrus showed significant interaction effects
      between disease status (i.e., ADHD or TD) and age (i.e., child, adolescent, or
      adult) (P < 0.001). Additional regions were identified at a relaxed threshold (P
      < 0.05). Many of the identified regions (the left inferior frontal gyrus, the
      left middle temporal gyrus, and the left insular gyrus) were related to cognitive
      function. The results of our study suggest that aberrant development in cognitive
      brain regions might be associated with age-related brain network changes in ADHD
      patients. These findings contribute to better understand how brain function
      influences the symptoms of ADHD.

PMID- 29171430
TI  - Toxic effect of acrylamide on the development of hippocampal neurons of weaning
      rats.
AB  - Although numerous studies have examined the neurotoxicity of acrylamide in adult
      animals, the effects on neuronal development in the embryonic and lactational
      periods are largely unknown. Thus, we examined the toxicity of acrylamide on
      neuronal development in the hippocampus of fetal rats during pregnancy. Sprague
      Dawley rats were mated with male rats at a 1:1 ratio. Rats were administered 0,
      5, 10 or 20 mg/kg acrylamide intragastrically from embryonic days 6-21. The gait
      scores were examined in pregnant rats in each group to analyze maternal toxicity.
      Eight weaning rats from each group were also euthanized on postnatal day 21 for
      follow-up studies. Nissl staining was used to observe histological change in the
      hippocampus. Immunohistochemistry was conducted to observe the condition of
      neurites, including dendrites and axons. Western blot assay was used to measure
      the expression levels of the specific nerve axon membrane protein, growth
      associated protein 43, and the presynaptic vesicle membrane specific protein,
      synaptophysin. The gait scores of gravid rats significantly increased, suggesting
      that acrylamide induced maternal motor dysfunction. The number of neurons, as
      well as expression of growth associated protein 43 and synaptophysin, was reduced
      with increasing acrylamide dose in postnatal day 21 weaning rats. These data
      suggest that acrylamide exerts dose-dependent toxic effects on the growth and
      development of hippocampal neurons of weaning rats.

PMID- 29171431
TI  - Effect of erythropoietin combined with hypothermia on serum tau protein levels
      and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.
AB  - Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic
      encephalopathy, many neonatal patients die or suffer from severe neurological
      dysfunction. Erythropoietin is considered one of the most promising
      neuroprotective agents. We hypothesized that erythropoietin combined with
      hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy
      treatment. In this study, 41 neonates with moderate/severe hypoxic-ischemic
      encephalopathy were randomly divided into a control group (hypothermia alone for
      72 hours, n = 20) and erythropoietin group (hypothermia + erythropoietin 200
      IU/kg for 10 days, n = 21). Our results show that compared with the control
      group, serum tau protein levels were lower and neonatal behavioral neurological
      assessment scores higher in the erythropoietin group at 8 and 12 days. However,
      neurodevelopmental outcome was similar between the two groups at 9 months of age.
      These findings suggest that erythropoietin combined with hypothermia reduces
      serum tau protein levels and improves neonatal behavioral neurology outcome but
      does not affect long-term neurodevelopmental outcome.

PMID- 29171432
TI  - Locomotor analysis identifies early compensatory changes during disease
      progression and subgroup classification in a mouse model of amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is
      challenging to diagnose and presents with considerable variability in survival.
      Early identification and enhanced understanding of symptomatic patterns could aid
      in diagnosis and provide an avenue for monitoring disease progression. Use of the
      mSOD1G93A mouse model provides control of the confounding environmental factors
      and genetic heterogeneity seen in amyotrophic lateral sclerosis patients, while
      investigating underlying disease-induced changes. In the present study, we
      performed a longitudinal behavioral assessment paradigm and identified an early
      hindlimb symptom, resembling the common gait abnormality foot drop, along with an
      accompanying forelimb compensatory mechanism in the mSOD1G93A mouse. Following
      these initial changes, mSOD1 mice displayed a temporary hindlimb compensatory
      mechanism resembling an exaggerated steppage gait. As the disease progressed,
      these compensatory mechanisms were not sufficient to sustain fundamental
      locomotor parameters and more severe deficits appeared. We next applied these
      initial findings to investigate the inherent variability in B6SJL mSOD1G93A
      survival. We identified four behavioral variables that, when combined in a
      cluster analysis, identified two subpopulations with different disease
      progression rates: a fast progression group and a slow progression group. This
      behavioral assessment paradigm, with its analytical approaches, provides a method
      for monitoring disease progression and detecting mSOD1 subgroups with different
      disease severities. This affords researchers an opportunity to search for genetic
      modifiers or other factors that likely enhance or slow disease progression. Such
      factors are possible therapeutic targets with the potential to slow disease
      progression and provide insight into the underlying pathology and disease
      mechanisms.

PMID- 29171433
TI  - Protective effects of Bushen Tiansui decoction on hippocampal synapses in a rat
      model of Alzheimer's disease.
AB  - Bushen Tiansui decoction is composed of six traditional Chinese medicines: Herba
      Epimedii, Radix Polygoni multiflori, Plastrum testudinis, Fossilia Ossis Mastodi,
      Radix Polygalae, and Rhizoma Acorus tatarinowii. Because Bushen Tiansui decoction
      is effective against amyloid beta (Abeta) toxicity, we hypothesized that it would
      reduce hippocampal synaptic damage and improve cognitive function in Alzheimer's
      disease. To test this hypothesis, we used a previously established animal model
      of Alzheimer's disease, that is, microinjection of aggregated Abeta25-35 into the
      bilateral brain ventricles of Sprague-Dawley rats. We found that long-term (28
      days) oral administration of Bushen Tiansui decoction (0.563, 1.688, and 3.375
      g/mL; 4 mL/day) prevented synaptic loss in the hippocampus and increased the
      expression levels of synaptic proteins, including postsynaptic density protein
      95, the N-methyl-D-aspartate receptor 2B subunit, and Shank1. These results
      suggested that Bushen Tiansui decoction can protect synapses by maintaining the
      expression of these synaptic proteins. Bushen Tiansui decoction also ameliorated
      measures reflecting spatial learning and memory deficits that were observed in
      the Morris water maze (i.e., increased the number of platform crossings and the
      amount of time spent in the target quadrant and decreased escape latency)
      following intraventricular injections of aggregated Abeta25-35 compared with
      those measures in untreated Abeta25-35-injected rats. Overall, these results
      provided evidence that further studies on the prevention and treatment of
      dementia with this traditional Chinese medicine are warranted.

PMID- 29171434
TI  - Nischarin-siRNA delivered by polyethylenimine-alginate nanoparticles accelerates
      motor function recovery after spinal cord injury.
AB  - A previous study by our group found that inhibition of nischarin promotes neurite
      outgrowth and neuronal regeneration in Neuro-2a cells and primary cortical
      neurons. In recent years, more and more studies have shown that nanomaterials
      have good prospects in treatment of spinal cord injury. We proposed that small
      interfering RNA targeting nischarin (Nis-siRNA) delivered by polyethyleneimine
      alginate (PEI-ALG) nanoparticles promoted motor function recovery in rats with
      spinal cord injury. Direct microinjection of 5 MUL PEI-ALG/Nis-siRNA into the
      spinal cord lesion area of spinal cord injury rats was performed. From day 7
      after surgery, Basso, Beattie and Bresnahan score was significantly higher in
      rats from the PEI-ALG/Nis-siRNA group compared with the spinal cord injury group
      and PEI-ALG/Control-siRNA group. On day 21 after injection, hematoxylin-eosin
      staining showed that the necrotic area was reduced in the PEI-ALG/Nis-siRNA
      group. Immunohistochemistry and western blot assay results confirmed successful
      inhibition of nischarin expression and increased protein expression of growth
      associated protein-43 in the PEI-ALG/Nis-siRNA group. These findings suggest that
      a complex of PEI-ALG nanoparticles and Nis-siRNA effectively suppresses nischarin
      expression, induces expression of growth-associated protein-43, and accelerates
      motor function recovery after spinal cord injury.

PMID- 29171435
TI  - Central projections and connections of lumbar primary afferent fibers in adult
      rats: effectively revealed using Texas red-dextran amine tracing.
AB  - Signals from lumbar primary afferent fibers are important for modulating
      locomotion of the hind-limbs. However, silver impregnation techniques,
      autoradiography, wheat germ agglutinin-horseradish peroxidase and cholera toxin B
      subunit-horseradish peroxidase cannot image the central projections and
      connections of the dorsal root in detail. Thus, we injected 3-kDa Texas red
      dextran amine into the proximal trunks of L4 dorsal roots in adult rats. Confocal
      microscopy results revealed that numerous labeled arborizations and varicosities
      extended to the dorsal horn from T12-S4, to Clarke's column from T10-L2, and to
      the ventral horn from L1-5. The labeled varicosities at the L4 cord level were
      very dense, particularly in laminae I-III, and the density decreased gradually in
      more rostral and caudal segments. In addition, they were predominately
      distributed in laminae I-IV, moderately in laminae V-VII and sparsely in laminae
      VIII-X. Furthermore, direct contacts of lumbar afferent fibers with propriospinal
      neurons were widespread in gray matter. In conclusion, the projection and
      connection patterns of L4 afferents were illustrated in detail by Texas red
      dextran amine-dorsal root tracing.

PMID- 29171436
TI  - End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces
      motor nerve regeneration.
AB  - End-to-side neurorrhaphy is an option in the treatment of the long segment
      defects of a nerve. It involves suturing the distal stump of the disconnected
      nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve).
      However, the motor-sensory specificity after end-to-side neurorrhaphy remains
      unclear. This study sought to evaluate whether cutaneous sensory nerve
      regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats
      were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar
      nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii
      medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and
      cutaneous antebrachii medialis nerve were just exposed; and (3) the transected
      nerve group: cutaneous antebrachii medialis nerve was transected and the stumps
      were turned over and tied. At 5 months, acetylcholinesterase staining results
      showed that 34% +/- 16% of the myelinated axons were stained in the end-to-side
      group, and none of the myelinated axons were stained in either the sham or
      transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons
      and dorsal root ganglion showed the proportion of motor neurons from the
      cutaneous antebrachii medialis nerve of the end-to-side group was 21% +/- 5%. In
      contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the
      sham group and transected nerve group were found in the spinal cord segment.
      These results confirmed that motor neuron regeneration occurred after cutaneous
      nerve end-to-side neurorrhaphy.

PMID- 29171437
TI  - miR-30c promotes Schwann cell remyelination following peripheral nerve injury.
AB  - Differential expression of miRNAs occurs in injured proximal nerve stumps and
      includes miRNAs that are firstly down-regulated and then gradually up-regulated
      following nerve injury. These miRNAs might be related to a Schwann cell
      phenotypic switch. miR-30c, as a member of this group, was further investigated
      in the current study. Sprague-Dawley rats underwent sciatic nerve transection and
      proximal nerve stumps were collected at 1, 4, 7, 14, 21, and 28 days post injury
      for analysis. Following sciatic nerve injury, miR-30c was down-regulated,
      reaching a minimum on day 4, and was then upregulated to normal levels. Schwann
      cells were isolated from neonatal rat sciatic nerve stumps, then transfected with
      miR-30c agomir and co-cultured in vitro with dorsal root ganglia. The enhanced
      expression of miR-30c robustly increased the amount of myelin-associated protein
      in the co-cultured dorsal root ganglia and Schwann cells. We then modeled sciatic
      nerve crush injury in vivo in Sprague-Dawley rats and tested the effect of
      perineural injection of miR-30c agomir on myelin sheath regeneration. Fourteen
      days after surgery, sciatic nerve stumps were harvested and subjected to
      immunohistochemistry, western blot analysis, and transmission electron
      microscopy. The direct injection of miR-30c stimulated the formation of myelin
      sheath, thus contributing to peripheral nerve regeneration. Overall, our findings
      indicate that miR-30c can promote Schwann cell myelination following peripheral
      nerve injury. The functional study of miR-30c will benefit the discovery of new
      therapeutic targets and the development of new treatment strategies for
      peripheral nerve regeneration.

PMID- 29171438
TI  - In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root
      ganglion neurons with glutamate-induced neurotoxicity.
AB  - Ciliary neurotrophic factor has neuroprotective effects mediated through signal
      transducer and Janus kinase (JAK) 2/activator of transcription 3 (STAT3) and
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Whether ciliary
      neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of
      dorsal root ganglion neurons is poorly understood. In the present study, the in
      vitro neuroprotective effects of ciliary neurotrophic factor against glutamate
      induced excitotoxicity were determined in a primary culture of dorsal root
      ganglion neurons from Wistar rat embryos at embryonic day 15. Whether the
      JAK2/STAT3 and PI3K/Akt signaling pathways were related to the protective effects
      of ciliary neurotrophic factor was also determined. Glutamate exposure inhibited
      neurite outgrowth, cell viability, and growth-associated protein 43 expression
      and promoted apoptotic neuronal cell death, all of which were reversed by the
      administration of exogenous ciliary neurotrophic factor. Additionally,
      preincubation with either JAK2 inhibitor AG490 or PI3K inhibitor LY294002 blocked
      the neuroprotective effect of ciliary neurotrophic factor. These data indicate
      that the two pathways JAK2/STAT3 and PI3K/Akt play major roles in mediating the
      in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root
      ganglion neurons with glutamate-induced neurotoxicity.

PMID- 29171439
TI  - Effect of glial cells on remyelination after spinal cord injury.
AB  - Remyelination plays a key role in functional recovery of axons after spinal cord
      injury. Glial cells are the most abundant cells in the central nervous system.
      When spinal cord injury occurs, many glial cells at the lesion site are
      immediately activated, and different cells differentially affect inflammatory
      reactions after injury. In this review, we aim to discuss the core role of
      oligodendrocyte precursor cells and crosstalk with the rest of glia and their
      subcategories in the remyelination process. Activated astrocytes influence
      proliferation, differentiation, and maturation of oligodendrocyte precursor
      cells, while activated microglia alter remyelination by regulating the
      inflammatory reaction after spinal cord injury. Understanding the interaction
      between oligodendrocyte precursor cells and the rest of glia is necessary when
      designing a therapeutic plan of remyelination after spinal cord injury.

PMID- 29171442
TI  - Tuberculosis serodiagnostics: Ban and after.

PMID- 29171441
TI  - Diffusion tensor tractography studies on mechanisms of recovery of injured
      fornix.
AB  - The fornix, which connects the medial temporal lobe and the medial diencephalon,
      is involved in episodic memory as an important part of the Papez circuit. The
      mechanisms of recovery of an injured fornix revealed by diffusion tensor
      tractography in the five studies are summarized as follows: 1) recovery through
      the nerve tract from an injured fornical crus to the medial temporal lobe via the
      normal pathway of the fornical crus; 2) recovery through the nerve tract
      originating from an ipsi-lesional fornical body connected to the ipsi-lesional
      medial temporal lobe via the splenium of the corpus callosum; 3) recovery through
      the nerve tract from the ipsi-lesional fornical body extending to the contra
      lesional medial temporal lobe via the splenium of the corpus callosum; 4)
      recovery through the nerve tract originating from the ipsi-lesional fornical
      column connected to the ipsi-lesional medial temporal lobe; and 5) recovery
      through the nerve tract originating from the contra-lesional fornical column
      connected to the ipsi-lesional medial temporal lobe via the contra-lesional
      medial temporal lobe and the splenium of the corpus callosum. These diffusion
      tensor tractography studies on mechanisms of recovery of injured fornical crus
      appeared to provide useful information for clinicians caring for patients with
      brain injury, however, studies on this topic are still in the beginning stages.

PMID- 29171440
TI  - Brain-derived neurotropic factor and GABAergic transmission in neurodegeneration
      and neuroregeneration.
AB  - Neurotoxicity induced by stress, radiation, chemicals, or metabolic diseases, is
      commonly associated with excitotoxicity, oxidative stress, and neuroinflammation.
      The pathological process of neurotoxicity induces neuronal death, interrupts
      synaptic plasticity in the brain, and is similar to that of diverse
      neurodegenerative diseases. Animal models of neurotoxicity have revealed that
      clinical symptoms and brain lesions can recover over time via neuroregenerative
      processes. Specifically, brain-derived neurotropic factor (BDNF) and gamma
      aminobutyric acid (GABA)-ergic transmission are related to both neurodegeneration
      and neuroregeneration. This review summarizes the accumulating evidences that
      suggest a pathogenic role of BDNF and GABAergic transmission, their underlying
      mechanisms, and the relationship between BDNF and GABA in neurodegeneration and
      neuroregeneration. This review will provide a comprehensive overview of the
      underlying mechanisms of neuroregeneration that may help in developing potential
      strategies for pharmacotherapeutic approaches to treat neurotoxicity and
      neurodegenerative disease.

PMID- 29171443
TI  - Risk factors for tuberculosis and beyond.

PMID- 29171444
TI  - Role of Vitamins B, C, and D in the fight against tuberculosis.
AB  - Worldwide, tuberculosis (TB) is still a serious and significant health concern,
      more so with the emergence of multidrug-resistant-TB. The inability of mankind to
      control this infection stems from the fact that the vaccines and drugs that were
      once effective against TB are no longer efficacious. This has led to a search for
      new antituberculous agents and adjuvant therapy. Vitamins are being revisited for
      their role in pathogenicity as well as for their antimycobacterial properties.
      Vitamins such as biotin and thiamin are essential for Mycobacterium tuberculosis
      and are required for establishment of infection. On the other hand, vitamins such
      as Vitamin C and Vitamin D have been shown to possess antimycobacterial
      properties. To combat M. tuberculosis, innovative strategies need to be devised,
      keeping in mind the efficacy of the agent to be used. Vitamins can prove to be
      useful agents capable of modifying the life cycle and biology of M. tuberculosis.
      We present here a brief overview of the available knowledge on thiamin, biotin,
      Vitamin C, and Vitamin D, keeping TB treatment and control in perspective.

PMID- 29171445
TI  - The epidemiology of tuberculous dactylitis: A case report and review of
      literature.
AB  - The literature on tuberculous dactylitis is poor, and most literature consists of
      isolated case reports. The aim of this case series is to study the
      particularities and the epidemiological aspects of tuberculous dactylitis in
      Tunisian patients. Google and Medline search was done using key words
      "tuberculous dactylitis" and "spina ventosa." Only Tunisian reports in adult
      patients were included. Eleven cases including this mentioned case were included
      in this review. There was a female predominance, high frequency of trauma before
      disease installation, rarity of predisposing factors, and less inflammation in
      blood tests when comparing with other cases in literature.

PMID- 29171446
TI  - Do infections with disseminated Mycobacterium avium complex precede sweet's
      syndrome? A case report and literature review.
AB  - Sweet's syndrome is reportedly associated with preceding nontuberculous
      mycobacterial infections (NTMIs). Here, we report on a systemic Mycobacterium
      intracellulare infection in a patient on corticoid therapy for Sweet's syndrome.
      Literature searches show that 69.1% of patients with Sweet's syndrome and NTMIs
      developed this syndrome later than NTMIs and 89.3% of them developed during the
      clinical course of a rapidly growing mycobacterial infection. The residual cases
      were associated with slow-growing mycobacteria (14.3%), but only three cases of
      Mycobacterium avium complex (MAC) infections before the onset of Sweet's syndrome
      have been reported, and all of them were caused by disseminated MAC disease. One
      of these cases developed during corticoid therapy for Sweet's syndrome, while
      another case had underlying diabetes mellitus. Hence, the occurrence of systemic
      MAC disease may be an inevitable consequence of long-term steroid use and
      underlying diseases. Literature searches also show that cervical lymphadenitis
      was a predominant symptom in NTMIs (90.5%). The present case did not have
      cervical lymphadenitis although the previously reported MAC cases did experience
      it. Therefore, lymphadenitis from NTMIs may be related to the pathogenesis of
      Sweet's syndrome. Hence, should a patient have systemic infection without
      lymphadenitis, it will be more difficult to clinically confirm that MAC disease
      is a predisposing factor for Sweet's syndrome.

PMID- 29171447
TI  - Nontuberculous mycobacteria in a tertiary Hospital in Portugal: A clinical
      review.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) form a heterogeneous group
      regarding their ability to cause disease. To further understand their clinical
      relevance, the characteristics of patients who had positive cultures for NTM at a
      tertiary hospital in Portugal were reviewed. METHODS: Retrospective analysis of
      patients assessed at the Infectious Diseases (ID) Department of the Sao Joao
      Hospital Center, from January 2007 to December 2014, from whom at least one
      biological sample was tested culture positive for NTM. RESULTS: A total of 74
      patients with at least one positive culture for NTM were identified. Forty-nine
      (66.2%) were infected by the human immunodeficiency virus, 4 (5.4%) had cancer,
      and 7 (9.5%) were under immunosuppressive medication. A total of 13 patients
      (17.6%) fulfilled the American Thoracic Society/ID Society of America criteria
      for pulmonary NTM disease and treatment was initiated in 12 other patients
      (16.2%), all of which were immunocompromised. Mycobacterium avium complex was
      more frequently associated with disease, responsible for 56% of the patients
      treated. Patients were treated with antituberculosis drugs adjusted for the
      species isolated, and cure was achieved in 13 patients (52%). CONCLUSION: The
      present study highlights the importance of understanding the epidemiology of NTM
      to better comprehend their clinical impact.

PMID- 29171448
TI  - Vitamin D, cell death pathways, and tuberculosis.
AB  - BACKGROUND: Mycobacterium tuberculosis induces cellular necrosis that could
      promote spread of infection. The aim of this study is to analyze the effects of
      Vitamin D3 supplementation to improve the effectiveness of 2nd-line anti
      tuberculosis (TB) drug therapy, especially in relation with cell death pathways.
      METHODS: Mus musculus C3HeB/FeJ was randomly divided into four groups containing
      eight animals each. The 1st group (G1), consisting of mice that were
      intratracheally infected with multidrug-resistant strain of M. tuberculosis and
      sacrificed on 2-week postinfection to confirm successful infection. (G2) was a
      group of TB mice without therapy. Then, (G3) was a group of mice with the 2nd
      line anti-TB therapy. The last group (G4) was a group of mice receiving not only
      the 2nd-line anti-TB therapy but also daily oral Vitamin D3 supplementation.
      Immunohistochemistry was used to measure expression of nuclear Vitamin D
      receptor, apoptosis marker cleaved caspase-3, cathelin-related antimicrobial
      peptide (CRAMP) and LC3B autophagy markers, necrosis marker RIPK3, and
      collagenase matrix metalloproteinase-1 (MMP1). The number of bacteria in the lung
      was calculated by colony forming units. The partial least square structural
      equation modeling with SmartPLS 3.2.6 software was used to analyze structural
      models among the variables. RESULTS: Supplementation of Vitamin D3 on the 2nd
      line anti-TB therapy increases Vitamin D3 receptor, CRAMP, LC3B, caspase-3 (P =
      0.026, P = 0.000, P= 0.001), presses MMP1, and the number of bacteria (P = 0.010
      and P= 0.000, respectively). The structural equation modeling analysis shows that
      increasing autophagy pathways reduces necrosis by lowering MMP1, whereas
      apoptosis reduces necrosis by decreasing the number of bacteria (each with
      indirect effects - 0.543 and - 0.544). CONCLUSION: A comprehensive analysis with
      the partial least square structural equation modeling shows decreasing necrosis
      requires increasing autophagy and apoptosis.

PMID- 29171449
TI  - Risk factors for tuberculosis mortality in a tertiary care center in Oman, 2006
      2016.
AB  - BACKGROUND: Mortality from tuberculosis (TB) remains high despite its declining
      global incidence. Host risk factors of TB death have not been fully identified.
      The aim of this study is to explore some of the host risk factors associated with
      TB mortality. METHODS: We conducted a retrospective cross-sectional review of
      patients with TB admitted to Sultan Qaboos University Hospital in Oman from July
      2006 to February 2016. Multivariate logistic regression analyses were used to
      evaluate the risk factors for TB mortality. RESULTS: Of the 205 TB cases
      reviewed, we identified 31 (15%) TB deaths during TB treatment. The median time
      of death from starting TB drugs was 30 days. Fifty-one percent of the TB deaths
      occurred in the 1st month of TB diagnosis. The main risk factors for TB mortality
      were advanced age, low body weight, negative sputum TB smear, pulmonary
      involvement, human immunodeficiency virus infection, and noncitizen status.
      CONCLUSION: To improve TB outcome in this high-risk group, abrupt clinical
      management approaches should be applied when TB is suspected. Public health
      measures that increase community awareness of TB mortality and reduce barriers to
      TB care are crucial to reducing TB mortality.

PMID- 29171450
TI  - Treatment outcome of tuberculosis patients under directly observed treatment
      short course and its determinants in Shangla, Khyber-Pakhtunkhwa, Pakistan: A
      retrospective study.
AB  - BACKGROUND: Tuberculosis (TB) is one of the leading causes of morbidity and
      mortality in Pakistan. Assessment of TB treatment outcomes, monitoring and
      evaluation of its risk factors in Directly Observed Treatment Short Course (DOTS)
      are among the major indicators of the performance of a national TB control
      program. Even though Pakistan ranks 5th among the 22 high-TB burden countries,
      there are no available data in this regard. METHODS: Institution-based
      retrospective study was conducted to determine the treatment outcome of TB
      patients and investigate associated risk factors at District Head Quarter
      Hospital Shangla, Khyber-Pakhtunkhwa, Pakistan. Two-year record (January 2011 to
      December 2012) of TB clinic of the hospital was reviewed. A total of 493
      patients' complete information was reviewed in the study period. RESULTS: Of
      these, 42.19% were smear-positive pulmonary TB (PTB), 35.09% were smear-negative
      PTB, and 22.72% were extra-PTB (EPTB). The overall prevalence of smear-positive
      PTB was 42.19% (95% confidence interval [CI]: 37.9-46.2). Records of the
      treatment outcome showed that 192 (38.94%) were cured, 276 (55.98%) completed
      treatment, 13 (2.6%) defaulted, 9 (1.8%) died, 1 (0.2%) treatment failure, and 1
      (0.2%) had transferred to other facilities. The overall mean treatment success
      rate of the TB patients was 94.93%. TB age and TB form or baseline smear were
      significantly associated with unsuccessful treatment outcome. The risk of
      unsuccessful outcome was significantly lower among TB patients age Conclusion:
      The treatment success rate was high and match the World Health Organization
      criteria. To sustain the effective implementation of DOTS in the area, effective
      management, and diagnosis should be given for EPTB.

PMID- 29171451
TI  - Sequence homology and expression profile of genes associated with DNA repair
      pathways in Mycobacterium leprae.
AB  - BACKGROUND: Survival of Mycobacterium leprae, the causative bacteria for leprosy,
      in the human host is dependent to an extent on the ways in which its genome
      integrity is retained. DNA repair mechanisms protect bacterial DNA from damage
      induced by various stress factors. The current study is aimed at understanding
      the sequence and functional annotation of DNA repair genes in M. leprae. METHODS:
      T he genome of M. leprae was annotated using sequence alignment tools to identify
      DNA repair genes that have homologs in Mycobacterium tuberculosis and Escherichia
      coli. A set of 96 genes known to be involved in DNA repair mechanisms in E. coli
      and Mycobacteriaceae were chosen as a reference. Among these, 61 were identified
      in M. leprae based on sequence similarity and domain architecture. The 61 were
      classified into 36 characterized gene products (59%), 11 hypothetical proteins
      (18%), and 14 pseudogenes (23%). All these genes have homologs in M. tuberculosis
      and 49 (80.32%) in E. coli. A set of 12 genes which are absent in E. coli were
      present in M. leprae and in Mycobacteriaceae. These 61 genes were further
      investigated for their expression profiles in the whole transcriptome microarray
      data of M. leprae which was obtained from the signal intensities of 60bp probes,
      tiling the entire genome with 10bp overlaps. RESULTS: It was noted that
      transcripts corresponding to all the 61 genes were identified in the
      transcriptome data with varying expression levels ranging from 0.18 to 2.47 fold
      (normalized with 16SrRNA). The mRNA expression levels of a representative set of
      seven genes ( four annotated and three hypothetical protein coding genes) were
      analyzed using quantitative Polymerase Chain Reaction (qPCR) assays with RNA
      extracted from skin biopsies of 10 newly diagnosed, untreated leprosy cases. It
      was noted that RNA expression levels were higher for genes involved in homologous
      recombination whereas the genes with a low level of expression are involved in
      the direct repair pathway. CONCLUSION: This study provided preliminary
      information on the potential DNA repair pathways that are extant in M. leprae and
      the associated genes.

PMID- 29171453
TI  - Antibiotic resistance in Mycobacterium Abscessus and Mycobacterium Fortuitum
      isolates from Malaysian patients.
AB  - BACKGROUND: Rapidly growing mycobacterial species (RGM) are increasingly being
      recognized as the cause of various superficial and deep infections in humans. Two
      of the species most frequently isolated from clinical specimens are Mycobacterium
      abscessus and Mycobacterium fortuitum. Both species are associated with
      antibiotic resistances that may complicate therapy. This paper describes the
      pattern of resistance to five antibiotics commonly prescribed for RGM infections,
      in M. abscessus and M. fortuitum isolated from Malaysian patients. METHODS: The
      bacterial strains studied were examined with Etest strips to determine their
      minimum inhibitory concentrations (MICs) toward amikacin, ciprofloxacin,
      clarithromycin, imipenem, and linezolid. RESULTS: Among 51 M. abscessus isolates
      examined by the Etest, the overall MICs of ciprofloxacin, imipenem, amikacin,
      clarithromycin, and linezolid showed resistance rates of 33.3%, 31.4%, 2.0%,
      5.9%, and 21.6%, to the five antibiotics, respectively. M. abscessus subspecies
      abscessus was more resistant than M. abscessus subsp. massilience to
      ciprofloxacin, imipenem, and linezolid but was more susceptible to clarithromycin
      and amikacin. M. fortuitum isolates were significantly less resistant than M.
      abscessus to ciprofloxacin (3.6%) and imipenem (7.1%) but more resistant to
      clarithromycin (42.9%) and linezolid (39.3%). CONCLUSION: A suitable combination
      therapy for Malaysian patients would be amikacin plus clarithromycin and
      ciprofloxacin, to cover infections by all three M. abscessus subspecies and M.
      fortuitum.

PMID- 29171452
TI  - The most frequent Mycobacterium tuberculosis complex families in mali (2006-2016)
      based on spoligotyping.
AB  - BACKGROUND: To identify strains of Mycobacterium tuberculosis complex (MTBc)
      circulating in Bamako region during the past 10 years. METHODS: From 2006 to
      2016, we conducted a cross-sectional study to identify with spoligotyping,
      clinical isolates from tuberculosis (TB)-infected patients at different stages of
      their treatments in Bamako, Mali. RESULTS: Among the 904 suspected TB patients
      included in the study and thereafter tested in our BSL-3 laboratory, 492 (54.4%)
      had MTBc and therefore underwent spoligotyping. Overall, three subspecies, i.e.,
      MTB T1 (31.9%) and MTB LAM10 (15.3%) from lineage 4 and M. africanum 2 (16.8%)
      from lineage 6 were the leading causes of TB in Bamako region during the past 10
      years. Other spoligotypes such as MTB T3, MTB Haarlem 2, MTB EAI3, and MTB family
      33 were also commonly seen from 2010 to 2016. CONCLUSION: This study showed a
      high genetic diversity of strains isolated in Bamako region and highlights that
      M. tuberculosis T1 strain was the most prevalent. Furthermore, the data indicate
      an increasing proportion of primary drug resistance overtime in Bamako.

PMID- 29171454
TI  - Nontuberculous mycobacteria in clinical samples with negative acid-fast bacilli.
AB  - BACKGROUND: There is a progressive increase in nontuberculous mycobacteria (NTM)
      in pulmonary and extrapulmonary infections that might cause confusion with the
      Mycobacterium tuberculosis complex. To determine the frequency of finding NTM in
      clinical samples from patients diagnosed with active tuberculosis, with negative
      acid-alcohol-resistant bacilli (acid-fast bacillus [AFB]) in a third-level
      specialty hospital's mycobacterial laboratory between January 2013 and December
      2014. METHODS: This is a prospective, descriptive study where isolated strains of
      biological material were studied in Lowenstein-Jensen and BACTEC MGIT 960
      cultures. RESULTS: Clinical samples of 120 patients were studied, with pulmonary
      samples of 99/120 (82%) and extrapulmonary samples of 21/120 (18%). We identified
      NTM in 37/120 samples (30.8%), of which 16 in pulmonary, 13 in genitourinary, 3
      in bone marrow, and 5 in various specimens. Mycobacterium avium was isolated in
      20 samples, Mycobacterium intracellulare in seven samples, and various other
      species of NTM in the other 10 samples. CONCLUSION: To establish adequate
      treatment, we point out the importance of identifying the presence of NTM in the
      clinical samples of active tuberculosis patients with negative AFB, as possibly
      becoming confused with M. tuberculosis and which is essential in deciding which
      treatment is the most adequate.

PMID- 29171455
TI  - Association between effectiveness of tuberculosis treatment and cytochrome P
      4502E1 polymorphism of the patients.
AB  - CONTEXT: The risk of antituberculosis (TB) drug-induced liver injury could be
      determined by patients' genotype polymorphism of the xenobiotic-metabolizing
      enzymes. To find the meaning of cytochrome P-4502E1 (CYP2E1) polymorphism in TB
      patients. Corresponding of CYP2E1 polymorphism in TB patients with the level of
      isoniazid and rifampicin as well as for the outcome and toxicity development
      during inpatient TB treatment. METHODS: CYP2E1 genotype was detected with the
      help of polymerase chain reaction and endonuclease analysis. The level of
      rifampicin, isoniazid, diene conjugates (DC), and catalase activity in the blood
      was determined spectrophotometrically. We have considered medical records at the
      beginning and at the end of inpatient treatment. STATISTICAL ANALYSIS USED:
      Kruskal-Wallis, ANOVA, and Chi-square tests were used in this study. RESULTS: The
      concentration of rifampicin 6 h after its intake was 17.6% higher in carriers of
      slow metabolizer (SM) CYP2E1 genotype than in patients with rapid metabolizer
      (RM) genotype that proved a participation of hepatic enzyme CYP2E1 in metabolism
      of rifampicin. According to obtained results in TB patients with RM genotype, the
      indexes of cytolysis (alanine aminotransferase, aspartate aminotransferase) and
      bile stasis (gamma-glutathione transferase) were higher comparatively to SM
      genotype both before and after inpatient treatment. This correlated with a higher
      concentration of DC in the blood (+8.6%) and lower plasma catalase activity (
      50.0%) in the patients with RM genotype comparatively with the patients with SM
      genotypes. CONCLUSION: Polymorphism of CYP2E1 genotype is an important criterion
      for the development of hepatotoxicity before and during TB treatment while
      increased rifampicin level has no influence on it.

PMID- 29171456
TI  - Mycobacterium Interjectum isolated from an immunocompetent host with lung
      infection.
AB  - Improved molecular diagnostic techniques have resulted in increased reporting of
      nontuberculous mycobacterial infections. A 40-year-old male immunocompetent
      individual presented with cough and fever of 2-week duration. His chest X-ray
      showed cavities in the left upper zone and fibrosis in the right upper zone. His
      sputum was positive for AFB on Ziehl-Neelsen staining and showed slow-growing
      mycobacteria in mycobacteria growth indicator tube. The isolate was identified as
      Mycobacterium interjectum using GenoType(r) Mycobacterium CM assay (Hain
      Lifescience, GmBH, Nehren, Germany). At the end of a year's treatment, this first
      case from India has shown good progress.

PMID- 29171457
TI  - Tubercular colitis masquerading as ischemic colitis: An unusual presentation.
AB  - Tuberculosis is a common clinical problem which can involve virtually any organ
      and mimic a multitude of clinical conditions. Colonic tuberculosis is a type of
      intestinal tuberculosis which involves the colon and mimics inflammatory bowel
      disease. Occasionally, it is also confused with colonic malignancy. We report the
      case of a young female who presented with abdominal pain, bleeding per rectum.
      Abdominal X-ray showed evidence of thumb-printing. A possibility of ischemic
      colitis was entertained. However, further investigation unraveled the presence of
      tubercular colitis. The patient improved with anti-tubercular therapy. Colonic
      tuberculosis can mimic a number of clinical entities and should be considered in
      differential diagnosis of colonic lesions in endemic areas.

PMID- 29171458
TI  - Symmetrical peripheral gangrene and tuberculosis: A rare kinship.
AB  - Symmetrical peripheral gangrene (SPG) is a rare clinical syndrome characterized
      by ischemic necrosis of 2 or more limbs, without involvement of large vessels. It
      is often associated with disseminated intravascular coagulation and septic shock.
      Usually caused by Gram-positive and Gram-negative organisms, tuberculosis as a
      cause is extremely rare. We present the case of a 46-year-old man, who initially
      presented with signs and symptoms suggestive of tuberculosis but later developed
      SPG along with septic shock after his initial visit. The case highlights the
      progression of this dreaded complication and touches upon recent developments in
      its etiology as well as pathogenesis.

PMID- 29171459
TI  - Bilateral inguinal lymphadenopathy presenting as tuberculosis in a case of
      carcinoma rectum.
AB  - Isolated bilateral inguinal tubercular lymphadenitis is a very rare presentation.
      A 59-year-old male, on treatment for Carcinoma rectum (T3 N1 M0) presented with
      bilateral inguinal lymphadenopathy. Metastasis and tuberculosis were considered
      for differentials. FNAC of the lesion showed Necrotizing granulomatous
      lymphadenitis. There was regression of the lesion on both sides after two months
      of Anti-tubercular Therapy. Even though Metastasis is the commonest cause of
      inguinal lymphadenopathy in a case of carcinoma rectum, Tuberculosis needs to be
      considered in the differential diagnosis in our country. FNAC/Biopsy can be
      considered in those patients to confirm the diagnosis.

PMID- 29171460
TI  - Knowledge on tuberculosis in rural Myanmar.

PMID- 29171461
TI  - Quality assurance training course on chest radiography in Laos.

PMID- 29171462
TI  - [Description of postauthorisation observational prospective studies with drugs in
      the valencian region between 2010 and 2015. Factors associated with their
      authorisation.]
AB  - OBJECTIVE: Postauthorisation observational studies are crucial source of
      information on drug effectiveness and safety. The objectives of this work were to
      describe the characteristics of the postauthorisation observational prospective
      studies (EPA-SP) for which authorisation was requested in the Valencian region,
      as well as to explore which factors influenced the aforementioned authorisation.
      METHODS: We performed a retrospective analytical study comprising all the EPA-SP
      for which authorisation was requested in the Valencian region between 2010 and
      2015.The variables associated to the studies (e.g., objectives, studied drug,
      target disease) as well as those concerning the authorisation process itself
      (e.g., authorisation status, reason for authorisation refusal, current status of
      the study) were obtained from relevant databases. The analysis was divided into
      descriptive and analytical stages. RESULTS: We included a total of 249 studies,
      out of which 192 (77, 1%) aimed at estimating effectiveness or quality of life.
      The most frequent types of drugs involved in the studies were the antineoplastic
      and immunomodulating agents (42%). Only 57% of the studies were granted
      authorisation, with prescription induction and unusual practice being the most
      common causes for refusal (40.1% and 39.3%, respectively). The authorisation was
      linked to the diagnosis (circulatory system OR 10,7, IC95% 2,3 to 49,1), ATC L
      group (OR 4,2, IC95% 1,9 to 49,1) as well as to whether it had been advocated by
      the industry (OR 0,5, IC95% 0,3 to 0,9). CONCLUSIONS: Given the importance of
      having information on effectiveness and safety in usual practice, it is a
      priority for EPA-SP to be directed towards these aims and to promote independent
      research.

PMID- 29171463
TI  - [Is it possible to achieve sustained remission or cure of type 2 diabetes
      mellitus in the 21st century?]
AB  - A practitioner has a wide range of the hypoglycemic drugs for type 2 diabetes
      mellitus (T2DM) treatment, which can be used within a normal or near-normal range
      for long-term glycemic control. However, the question remains whether there are
      ways to achieve not only satisfactory glycemic control, but also T2DM remission
      (or even complete cure). The review presents an update on the concept of T2DM
      remission and describes the ways of its possible achievement with non-drug and
      drug treatments and surgery. The mechanisms of T2DM remission are given.

PMID- 29171464
TI  - [Impact of various wound dressings on wound bed neoangiogenesis in patients with
      different forms of diabetic foot syndrome].
AB  - AIM: To investigate the impact of various wound dressings on wound bed
      neoangiogenesis in patients with different forms of diabetic foot syndrome (DFS).
      SUBJECTS AND METHODS: The clinical (local tissue oxygenation) and
      immunohistochemical (CD31) markers of foot soft tissue neoangiogenesis were
      evaluated in patients with DFS receiving negative pressure (NP) therapy and
      collagen-containing dressings (CCDs) versus standard treatment. 63 patients with
      neuropathic and neuroischemic (without critical ischemia) forms of DFS were
      examined after wound debridement. In the postoperative period, 21 patients
      received NP treatment, CCDs were applied to 21 patients, and 21 patients had
      standard treatment. RESULTS: During NP therapy, there was statistically
      significantly intensified local microhemodynamics, as evidenced by transcutaneous
      oximetry (p < 0.05); the remaining two groups showed no statistically significant
      differences in transcutaneous oxygen tension during the treatment.
      Immunohistochemical examination revealed a significant increase in the number of
      newly formed vessels, as shown by anti-CD31 antibody staining (p < 0.05), in
      patients who had NP therapy and CCDs (p < 0.05). CONCLUSION: Vacuum (NP) therapy
      versus standard therapy most effectively affects wound bed neoangiogenesis. This
      is reflected in the increased local tissue microhemodynamics, as confirmed by
      immunohistochemical examination.

PMID- 29171465
TI  - [A 20-year prospective follow-up study to evaluate the development of retinopathy
      and nephropathy after the onset of type 1 diabetes mellitus: Contribution of
      glycemic control and metabolic memory].
AB  - AIM: To assess the time course of changes in the level of glycated hemoglobin
      (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to
      compare its correlation with the development of microvascular complications, such
      as diabetic retinopathy (DR) and diabetic nephropathy (DN). SUBJECTS AND METHODS:
      A total of 187 children with new-onset T1DM were registered in Moscow in 1994.
      During the 20-year follow-up study, these patients underwent regular check-ups at
      the Endocrinology Research Center, Ministry of Health of the Russian Federation,
      which included assessment of physical data, HbA1c 2-4 times a year, biochemical
      blood and albuminuria tests (once per year), and ophthalmologic examination
      (twice a year). A total of 155 people fully completed the 20-years follow-up
      study. RESULTS: During the 20-year follow-up period after the onset of T1DM, 86
      of the 155 patients developed microvascular complications: DR and DN in 86
      (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were
      noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no
      evidence suggesting the presence of microvascular complications. The level of
      HbA1c at the onset of the disease in patients who later developed the
      complications was higher than in those without complications (10.2+/-0.6 and
      8.5+/-0.2%, respectively (p = 0.003). The statistically significant differences
      in HbA1c levels between the groups persisted during subsequent 15 years of follow
      up, averaging 9.2+/-1.5, 9.7+/-0.9, and 8.1+/-0.7% after 5, 10, and 15 years,
      respectively, in the complication group and 7.1+/-0.3, 8.1+/-0.4, and 7.2+/-0.2%
      in the non-complication group (p < 0.01). Over the last 5 years of the follow-up,
      the mean HbA1c level between the groups was not significantly different, which at
      the end of the 20-year follow-up period was 7.8+/-0.3 and 7.4+/-0.6%,
      respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was
      9.6+/-6.2, 11.0+/-2.0, and 13.6+/-4.6 years for the non-proliferative, pre
      proliferative, and proliferative stages, respectively. That of T1DM, in which DN
      developed, was 11.8+/-0.6 years for microalbuminuria and 16.1+/-1.3 years for
      macroalbuminuria. CONCLUSION: The 20-year clinical follow-up of patients who had
      fallen ill with T1DM in childhood showed that diabetic microangiopathies
      developed with the long-term preservation of poor blood glucose control (BGC)
      starting at the onset of the disease. At the same time, the complications
      progressed to more severe stages, despite a clear trend toward better BGC. This
      may be suggestive of the negative metabolic memory phenomenon, which necessitates
      stable BGC, starting at the onset of the disease, for the prevention of
      microvascular complications.

PMID- 29171466
TI  - [The attitude of patients with types 1 and 2 diabetes mellitus towards having the
      disease].
AB  - AIM: To analyze the types of attitude towards disease, their relationships to its
      course in patients with diabetes mellitus (DM). SUBJECTS AND METHODS: 418
      patients with DM, including 318 with type 2 DM (T2DM) and 100 with Type 1 (T1DM),
      were examined. Clinical and laboratory examinations were performed; the types of
      attitude towards the disease were studied. RESULTS: The patients with T2DM were
      more frequently found to have anxious (12.9%) and hypochondriacal (10.7%) types
      of attitude towards the disease; those with T1DM had euphoric types. The
      paranoiac type of disease attitude, which was characterized by the presence of
      peculiar notions about the disease, was detected in 15.1% of the patients with
      T2DM and in 13% of those with T1DM. Hypernosognosia (overreaction to disease) was
      more often identified in T2DM (62.3% versus 39% in T1DM (chi2; p < 0.001). In the
      T2DM group, hypernosognosia was more frequently seen in women, unemployed
      persons, and obese patients. With the comparable awareness about the disease and
      degree of self-control, the patients with T2DM with no signs of hypernosognosia
      had a lower glycated hemoglobin level [7.35 (6.6; 8.6)%] than those with
      hypernosognosia [7.9 (7; 9.4)%] (p = 0.024). CONCLUSION: The revealed
      peculiarities of attitude towards the disease in patients with DM justify the
      need for increased attention to their psychological characteristics. The
      situation could be improved if the physicians are be informed, the time of
      outpatient care is prolonged, and psychotherapists and/or clinical psychologists
      are widely involved in the management of diabetic patients.

PMID- 29171467
TI  - [Microcirculatory parameters in compensated and decompensated type 2 diabetes
      mellitus].
AB  - AIM: To reveal the features of microcirculatory parameters in compensated and
      decompensated type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: A total of
      196 patients with T2DM were examined and divided into 2 groups: 1) 52 patients
      (40.4% of men) aged 52.8+/-8.7 years with compensated T2DM (glycated hemoglobin
      (HbA1s), 6.3+/-0.5%); 2) 68 patients (38.2% of men) aged 52.8+/-8.1 years with
      decompensated T2DM (HbA1s, 9.4+/-1.7%). Both patient groups had concomitant
      hypertension (its prevalence, degree, stage of hypertension were comparable). A
      control group consisted of 76 volunteers (40.8% of men) aged 52.2+/-8.7 years
      with normal carbohydrate metabolism and without signs of cardiovascular disease
      (HbA1s, 5.3+/-0.49%). Capillary blood flow in the finger nail-fold area was
      investigated in all the participants. A digital optical capillaroscope with image
      processing software was used to obtain quantitative blood microcirculatory
      parameters. The diameters of arterial and venous capillary segments were
      measured, by calculating the remodeling rate. The degree of capillary tortuosity,
      network density, and polymorphism and the size of the perivascular zone (PZ) were
      estimated. Blood rheological properties and capillary blood flow velocity were
      also investigated. RESULTS: The decompensated T2DM group compared to the
      compensated T2DM group was found to have a narrowing of the arterial capillary
      segment diameter (8.4+/-2.0 um; p=0.009) and an increase in remodeling rates
      (1.47+/-0.22; p=0.000). The tendency of the PZ size to be larger in patients with
      decompensated T2DM compared to those with compensated T2DM (p=0.080) and the
      increase in this indicator compared to the control group (p=0.001) reflect the
      presence of edema syndrome in Group 2, as laboratory confirmed by a statistically
      significantly elevated sodium level (p=0.000; p=0.006). The enlarged venous
      capillary segment demonstrates involvement of the venous component in
      microcirculatory disorders in T2DM. The reduction in the density of the capillary
      network and the increase in capillary tortuosity and polymorphism, which were
      also observed in the patients of both groups versus the control group, are
      referred to as disorders that are characteristic of T2DM. CONCLUSION: In
      decompensated T2DM, capillary bed structural and functional changes are found as
      a narrowing of the arterial capillary segment, an increase in the rate of
      remodeling, and enlargement of the PZ. Digital capillaroscopy opens up new
      possibilities for assessing the magnitude of changes in the microcirculatory
      system in DM and can simultaneously evaluate the efficiency of treatment, by
      monitoring the status of the microvasculature.

PMID- 29171468
TI  - [Glycemic variability and oxidative stress in patients with type 2 diabetes
      mellitus during combined glucose-lowering therapy].
AB  - AIM: To evaluate the impact of intensified glucose-lowering therapy on
      carbohydrate metabolic indicator, such as glycated hemoglobin, fasting blood
      glucose level (BGL) (FBGL), postprandial BGL (PBGL), and glycemic variability
      (GV) in patients with type 2 diabetes mellitus (T2DM) during metformin
      monotherapy before and 3 months after therapy intensification. SUBJECTS AND
      METHODS: The investigation enrolled 51 patients with T2DM treated with metformin
      1000 mg twice daily, who failed to achieve satisfactory glycemic control. During
      randomization, the treatment was intensified by addition of sitagliptin 100
      mg/day in Group 1 (n=25) or gliclazide MB 60 mg/day in Group 2 (n=26). Before and
      3 months after the treatment, carbohydrate metabolic indicators were
      investigated, 24-hour BGL monitoring (continuous glucose monitoring system (GMS))
      was performed, and the body's antioxidant status was examined by determining the
      total antioxidant capacity of blood plasma (overall sound pressure levels
      (OASPL)). RESULTS: During 3-month treatment, Group 1 had a significantly reduced
      FBGL compared to that before the therapy; in Group 2 this index did not change
      significantly. Both study groups showed a significant decrease in PBGL and
      glycated hemoglobin (HbA1c). The mean amplitude of glycemic excursion (MAGE) was
      significantly decreased in the sitagliptin intensification group. In both groups,
      the standard deviation (SD) reduced significantly by 26% in Group 1 and by 38% in
      Group 2. Both groups also displayed a significant increase in blood OASPL
      (p<0.05). CONCLUSION: The addition of sitagliptin significantly affected the
      change in the indicators of both the standard carbohydrate metabolism (FBGL,
      PBGL, and HbA1c) and GV (MAGE, SD), whereas that of gliclazide MV altered some
      studied parameters. OASPL significantly increased in both groups.

PMID- 29171469
TI  - [Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of
      ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms].
AB  - AIM: To analyze the association of genotype combinations of the polymorphic
      markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the
      TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz
      population. SUBJECTS AND METHODS: The investigation enrolled 23 Kyrgyz people, of
      whom there were 114 patients with T2DM and 109 without T2DM (a control group).
      T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of
      ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were
      identified using the restriction fragment length polymorphism analysis. RESULTS:
      When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the
      KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the
      Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68;
      p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene;
      the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype
      combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013),
      G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two
      locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/SS (OR, 1.97;
      p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC
      (OR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype
      combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48;
      p=0.02). CONCLUSION: The development of T2DM in the Kyrgyz population is
      genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L
      (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the
      heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1
      gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11
      (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS);
      KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys
      /CT). The IVS3C>T locus in the TCF7L2 gene is not independently statistically
      significantly associated with the development of T2DM; however, its predisposing
      effect has been identified in its combination with the variant genotypes of the
      polymorphic loci G276T in the ADIPOQ gene and Glu23Lys in the KCNJ11 gene.

PMID- 29171470
TI  - [Shereshevsky-Turner syndrome: Estrogen replacement therapy and cardiovascular
      risk factors].
AB  - AIM: To investigate the impact of menopausal hormone therapy (MHT) on the
      expression of risk factors for cardiovascular events (CVEs) in patients with
      Shereshevsky-Turner syndrome (STS); to elaborate an algorithm for patient
      management using MHT. SUBJECTS AND METHODS: From 2010 to 2012, a total of 41
      patients aged 14 to 35 years with STS were examined in the framework of a
      prospective observational study. 100 STS case histories in 2000 to 2009 were
      retrospectively analyzed. The indicators of the so-called cardiometabolic risk,
      such as body mass index (BMI), lipidogram readings, venous plasma glucose levels,
      and blood pressure, were estimated in relation to the type of MHT. In the
      prospective part of the investigation, an angioscan was used to estimate vessel
      characteristics (stiffness, wall tone, endothelial function (EF)), by using the
      examination data. RESULTS: 90% of the patients with STS were found to have risk
      factors for CVEs: atherogenic dyslipidemia (85%; 51% in the general female
      population of the same age), diastolic hypertension (36%; no more than 5% that is
      not typical for age-matched healthy general female population). In addition to
      increased arterial wall stiffness (AWS), obvious EF disorder is typical for STS
      patients. MHT was accompanied by a dose-dependent (estradiol, at least 2 mg)
      reduction in diastolic blood pressure by an average of 13% over 24 months, an
      increase in high density lipoprotein levels by more than 10% over 24 months and
      also contributedto a decrease in AWS and an improvement in EF. CONCLUSION: By
      favorably affecting the EF of vessels and reducing the severity of atherogenic
      dyslipidemia, MHT potentially enables a reduction in CV risk in patients with
      STS.

PMID- 29171471
TI  - [Associations between metabolic syndrome and reduced lung function in young
      people].
AB  - AIM: To reveal possible associations between metabolic syndrome (MS) and reduced
      lung function. SUBJECTS AND METHODS: In 2013-016, a cross-sectional survey was
      conducted in 908 Novosibirsk dwellers, which included spirometry to evaluate
      external respiratory function (ERF). For the detection of MS, the investigators
      used the 2009 All-Russian Research Society of Cardiologists criteria: waist
      circumference (WC) > 80 cm for women and >94 cm for men in combination with two
      of the following criteria: blood pressure (BP) >=130/85 mm Hg, triglycerides (TG)
      >=1.7 mmol/l, high-density lipoproteins (HDL) cholesterol <1.0 mmol/l for men and
      <1.2 mmol/l for women, low-density lipoprotein (LDL) cholesterol >3.0 mmol/l, and
      glucose >=6.1 mmol/l. RESULTS: The mean values of WC were significantly greater
      with a forced expiratory volume in one second (FEV1) <80% than those with a FEV1
      of >=80% in both men (p=0.002) and women (p=0.050); in women, the mean values of
      WS were higher than those with a FEV1/forced vital capacity (FVC) <70% than those
      with a FEV1/FVC of >=70% (p=0.047); the mean systolic and diastolic BP levels
      were significantly more with reductions in FEV1 and FVC, and the level of HDL
      cholesterol was significantly lower than that with a FEV1 of < 80% in men only.
      Significant correlations were found between FEV1 and all components of MS in men,
      between the majority of components of MS and FVC in men, between WC, BP, and
      FEV1/FVC in men and women, between plasma glucose levels and FEV1/FVC in women.
      Linear regression analysis revealed significant inverse correlations of FEV1 with
      TG, glucose, BP; those of FVC with TG, glucose; at the same time a positive
      association with HDL cholesterol in men, and only a negative correlation of
      FEV1/FVC with WC. CONCLUSION: The revealed associations between MS and reduced
      lung function can most likely be explained by the greater prevalence of both MS
      and its components (hypertension, hypertriglyceridemia, hyperglycemia, LDL
      hypercholesterolemia) among Novosibirsk men. This is consistent with the
      assertion that the decline in ERF, particularly FEV1, may be a marker of future
      cardiovascular disease morbidity and mortality.

PMID- 29171472
TI  - [CYP7A1 gene polymorphism and the characteristics of dyslipidemias in patients
      with nonalcoholic fatty liver disease concurrent with hypothyroidism].
AB  - AIM: To investigate the association of the polymorphic variants -204A > C (rs
      3808607) in the CYP7A1 gene with the development of dyslipidemias in healthy
      individuals, in patients with non-alcoholic fatty liver disease (NAFLD) and in
      those with NAFLD concurrent with hypothyroidism. SUBJECTS AND METHODS: DNA
      samples and lipidograms were examined in 180 patients, including 60 healthy
      individuals (Group 1), 60 patients with hypothyroidism concurrent with NAFLD
      (Group 2), and 60 patients with NAFLD (Group 3). All the patients underwent
      ultrasound examination of the thyroid gland and abdominal cavity organs; FibroMax
      scores were calculated. RESULTS: All the study groups most frequently showed a
      homozygous AA genotype (86.6% of cases in Group 1, 80% in Group 2, and 83.3% in
      Group 3). The development of NAFLD in CC genotype carriers is characterized by
      the most pronounced changes in lipid metabolism (atherogenic index (AI), 7.32 in
      Group 3) compared to the genotypes AA (AI, 4.56 in Group 2 and 1.73 in Group 1)
      and CC (AI, 6.43 in Group 2 and 2.52 in Group 1) in functional insufficiency of
      thyroid hormones and relative normal conditions. CONCLUSION: The analysis of the
      relationship of polymorphic variants CYP7A1 rs 38088607 to lipid metabolic
      disturbances in the study groups showed that the significantly higher levels of
      atherogenic cholesterol fractions were determined in the CC genotype compared to
      AA genotype carriers and they did not depend on the presence of NAFLD and
      hypothyroidism. The findings make it possible to consider the AA homozygous
      genotype of variant mutation CYP7A1 rs 38088607 as protective against
      dyslipidemia. However, in functional insufficiency of thyroid hormones, the level
      of triglycerides is significantly higher in both genotypes, which suggests that
      hypothyroidism plays an essential role in the development of dyslipidemia and
      NAFLD.

PMID- 29171473
TI  - [Time course of changes in cytokines (IFN-gamma, IFN-alpha, IL-18, TNF-alpha) in
      the treatment of moderate influenza A (H1N1) pdm09 (2013-2016) with oseltamivir
      (Tamiflu) and umifenovir (Arbidol) alone and in combination with Kagocel].
AB  - AIM: To assess correlation of cytokines levels and therapy regimes a relationship
      of the time course of changes in the cytokines IFN-gamma, IFN-alpha, IL-18, and
      TNF-alpha to the treatment option for influenza A (H1N1) pdm09 with umifenovir
      (Arbidol) 800 mg/day for 5 days (n=50); oseltamivir (Tamiflu) 150 mg/day for 5
      days (n=50); umifenovir (Arbidol) 800 mg/day for 5 days in combination with
      Kagocel 72 mg/day for 2 days.; 36 mg/day for 2 days (n=50); oseltamivir (Tamiflu)
      (150 mg/day for 5 days) in combination with Kagocel 72 mg/day for 2 days; 36
      mg/day for 2 days (n=50). A comparison group consisted of 30 healthy volunteers.
      MATERIAL AND METHODS: The state of immunologic reactivity was assessed twice: at
      admission of the patients to an infectious disease clinic (at 1-3 disease days)
      and in the early convalescent period (at 7-8 disease days): venous blood samples
      were collected to determine the concentrations of IFN-gamma, IFN-alpha, IL-18,
      and TNF-alpha by a solid-phase enzyme immunoassay. RESULTS: All the patients in
      the acute phase of influenza A showed a statistically significant increase in the
      levels of IFN-gamma, IFN-alpha, and IL-18 as compared with the control group. The
      groups receiving monotherapy in the early convalescent period had a decrease in
      the IFN-gamma, IFN-alpha, and IL-18 concentrations that could be compensated by
      the combined use of the immunomodulator Kagocel. No statistically significant
      changes in the levels of TNF-alpha were found in the patients of all the groups,
      but the groups receiving monotherapy exhibited its lower concentrations in the
      convalescence period. CONCLUSION: The combination of etiotropic antiviral drugs
      with Kagocel enhances the efficiency of antiviral therapy. Monitoring of
      antiviral cytokines during the treatment of influenza A is a convenient tool to
      verify the efficiency of antiviral therapy and needs to be more widely introduced
      into medical practice.

PMID- 29171474
TI  - [Progressive pulmonary hypertension in a patient with type 1 Gaucher disease].
AB  - Gaucher disease is the most common form of hereditary enzymopathies combined into
      a group of lysosomal storage diseases. The basis for the disease is a hereditary
      deficiency of the activity of acid beta-glucosidase, a lysosomal enzyme involved
      in the catabolism of lipids, which results in the accumulation of nonutilized
      cellular metabolism products in the macrophage lysosomes. The main clinical
      manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and
      splenomegaly, and bone lesion. One of the atypical clinical manifestations of
      Gaucher disease is damage to the lungs with the development of pulmonary
      hypertension, which is usually considered within the underlying disease - the
      development of pneumosclerosis due to macrophage dysfunction. The paper describes
      a case of progressive pulmonary hypertension in a patient with type 1 Gaucher
      disease.

PMID- 29171475
TI  - [Long-term consequences of polycystic ovary syndrome].
AB  - Polycystic ovary syndrome (PCOS) is the most common chronic endocrine disease in
      women. The prevailing complaints at a young age are menstrual irregularities,
      infertility, and hyperandrogenism-related problems. However, metabolic disorder
      induced complications have been in the foreground over years. The review gives
      the current ideas on a change of clinical manifestations in the natural course of
      PCOS, as well as the pathogenetically grounded prevention of complications in
      patients.

PMID- 29171476
TI  - [Recombinant human parathyroid hormone in the therapy of hypoparathyroidism].
AB  - Hypoparathyroidism is an endocrine disease that results from deficiency or
      complete absence of parathyroid hormone (PTH), a biologically active 84-amino
      acid polypeptide. Standard therapy for chronic hypoparathyroidism includes oral
      calcium salts and active vitamin D metabolites and is aimed at maintaining a
      balance between optimal near-normal serum calcium concentration and
      normocalcuria. Traditional treatment regimens not always lead to the compensation
      for calcium and phosphorus metabolism. Until recently, hypoparathyroidism is the
      only endocrine disorder that has not been treated with the recombinant hormone.
      To date, two recombinant PTH forms have been synthesized, which can be used as
      pathogenetic therapy for hypoparathyroidism. This review is dedicated to
      replacement therapy for hypoparathyroidism, by using both the full-length PTH
      molecule (1-84) and its shorter, but fully active, PTH form (1-34). This review
      considers stages in the developmental of hormone replacement therapy for
      hypoparathyroidism, discusses the most rational dosing regimens, and compares
      their efficacy and safety, as well as prospects for the development of this area.

PMID- 29171477
TI  - [Endothelial dysfunction and arterial wall stiffness: New targets in diabetic
      nephropathy].
AB  - In recent years, one of the promising areas in clinical medicine is the study of
      impaired ments in endothelial function and arterial wall stiffness, which can be
      referred to as one of the important predictors of cardiovascular events in
      patients with chronic kidney disease, including that of diabetic etiology. There
      is strong evidence that endothelial function and great artery stiffness may be
      used as reliable clinical and instrumental indicators to evaluate the efficiency
      of therapeutic measures and the rate of progression of cardiovascular disorders
      in type 2 diabetes mellitus. The article presents data on the role of endothelial
      dysfunction and arterial wall stiffness in the progression of chronic kidney
      disease in type 2 diabetes mellitus and discusses the possibility of their
      correction with pharmacological agents.

PMID- 29171478
TI  - [Enteral failure and metabolic syndrome: Common neurohormonal mechanisms of
      development, possibilities of their rational therapy].
AB  - The paper deals with small bowel (SB) functional disorders in metabolic syndrome
      (MS). The main components of a cascade of metabolic abnormalities in MS are
      closely due to SB functional changes. This is associated to some extent with the
      presence of common neurohormonal mechanisms in the development of enteropathy and
      MS. The paper gives the physical, laboratory and instrumental methods for
      identifying SB dysfunctions in patients with MS. Therapy for the latter is of
      particular interest in the context of SB functional recovery. The authors discuss
      the possibilities of enteropathy therapy in patients with MS; thus there is not
      only SB functional recovery, but also improved overall metabolic processes.

PMID- 29171479
TI  - [New aspects of Helicobacter pylori infection: Association with metabolic
      disturbances].
AB  - The review is devoted to the analysis of the literature on the possible
      association of Helicobacter pylori infection with type 2 diabetes mellitus,
      metabolic syndrome and its supposed mechanisms.

PMID- 29171480
TI  - [Ferrous sulfate in the treatment of iron deficiency anemia: The positions
      continue].
AB  - The paper discusses treatment strategy and tactics for iron deficiency anemia. It
      gives data on the comparative efficacy of different iron sulfate drugs, their
      bioavailability, effects on peroxidation processes, and side effects. The paper
      also considers the clinical significance of a dosage form of iron-containing
      drugs with a sustained iron release, as well as ways to reduce the frequency and
      magnitude of side effects when ferrous sulfate is used.

PMID- 29171481
TI  - [Current trends in the development of psychiatric care system].
AB  - In this article, the authors summarize current trends in the development of
      domestic and foreign mental health services, results of the reforms of national
      psychiatric services, and the state of inpatient and community-based psychiatric
      care systems. Actual problems and prospects of development of system of
      psychiatric help are discussed.

PMID- 29171482
TI  - [Sleep quality and hormone levels in the morning and evening hours under chemical
      pollution].
AB  - AIM: To evaluate self-assessment of sleep and the level of hormones in the
      morning and evening in chemical pollution conditions. MATERIAL AND METHODS: Three
      hundred adolescent and adult men living in the regions with low and high levels
      of chemical pollution were examined using questionnaires for self-assessment of
      quality of sleep, sleep hygiene, daytime sleepiness. Levels of cortisol and
      testosterone in the saliva were determined in the morning and evening hours by
      ELISA. RESULTS AND CONCLUSION: In areas with low pollution level, there were
      normal changes in hormone levels with an increase in the morning and decrease in
      the evening. In high pollution conditions, the average levels of hormones
      increased, the morning-evening gradient disappeared. These conditions were also
      associated with an increase in daytime sleepiness and disturbances in the sleep
      wake cycle and the endocrine regulation system that indicate the possibility of
      the development of internal desynchronosis.

PMID- 29171483
TI  - [Intermittent hypoxia due to sleep apnea syndrome in patients with type 2
      diabetes mellitus].
AB  - OBJECTIVES: To evaluate the possible association between intermittent hypoxia
      (IH) and HbA1c in patients with insufficient control type of 2 diabetes mellitus
      (T2DM). MATERIAL AND METHODS: In this cross-sectional study 183 patients with
      HbAc1>=7% underwent three-channel overnight monitoring (ApneaLink) and completed
      Berlin Questionnaire, Epworth Sleepiness Scale and Pittsburgh Sleep Quality
      Index. Patients were divided in two groups, based on the cut-off value of oxygen
      desaturation index>=15. RESULTS AND CONCLUSION: There were 79 (43%) patients with
      intermittent hypoxia, which was associated with poorer glycaemic control, defined
      as HbA1c>8.7% (sample median) in the univariate analysis and after adjustment for
      body mass index OR 2,40 (CI 1.21-4.95, p=0.021). Neither of three questionnaires
      yielded satisfactory results as a screening method in patients with T2DM. There
      is a need to implement instrumental screening of sleep-disordered breathing in
      this population and to study the effects of CPAP-therapy on glycaemic control and
      carbohydrate metabolism.

PMID- 29171484
TI  - [Sexual functioning and sexual dysfunction in women with infertility].
AB  - AIM: To study sexual dysfunction and assess the need in sexological care to
      improve quality of life of women with infertility. MATERIAL AND METHODS: Sexual
      functioning was studied in 329 women with infertility and 722 women who underwent
      an outpatient gynecological examination using a clinical interview and the Female
      Sexual Function Index (FSFI). RESULTS: In 24.01% of women with infertility, the
      total FSFI score was correlated with the presence of clinically relevant
      disorders. Sexual dysfunction was identified in 16.1% of women with infertility
      including libido disorder (84.9%), dyspareunia (30.2%) and orgasmic dysfunction
      (13.2%). The latent forms of sexual dysfunction were identified as well.
      CONCLUSION: The study showed a high need for curative and preventive sexological
      care to improve quality of life of women with infertility.

PMID- 29171485
TI  - [Intraoperative cerebroprotection in total intravenous anesthesia in children of
      school age].
AB  - AIM: To improve the quality of anesthesia in school-age children by using
      intraoperative metabolic-mediated cerebroprotection to reduce the incidence of
      cognitive impairment after total intravenous anesthesia based on propofol.
      MATERIAL AND METHODS: A randomized, prospective, longitudinal clinical study was
      conducted, involving 60 school-age children operated under total intravenous
      anesthesia on the basis of propofol. Children were randomized into two equal
      groups. Patients of the 1st group did not receive intraoperative metabolic
      mediated cerebroprotection, patients of the 2nd group were treated with
      cytoflavin. For Z-assessment of changes in cognitive potential,
      neuropsychological testing of 30 children of the same age who were not subjected
      to surgical intervention was performed. RESULTS AND CONCLUSION: On the 1st day of
      the postoperative period, 13.79% of patients of the 1st group had postoperative
      cognitive dysfunction (POCD), on the 7th day, POCD was observed in 26.67% of
      children. In the 2nd group, POCD was detected in 6.67% and 3.33% of patients on
      the 1st and 7th day, respectively (p=0,009). The results confirm the efficacy of
      cytoflavin in intraoperative prevention of POCD in school-age children.

PMID- 29171486
TI  - [Monitoring of neurotrophic factors and cognitive function in patients with
      traumatic brain injury].
AB  - AIM: To study the neurological and cognitive status in comparison to the
      quantitative content of blood serum neurotrophic factors of patients with acute
      and long-term brain injury during treatment with cerebrolysin. MATERIAL AND
      METHODS: Eighty patients, 56 men and 24 women, aged from 18 to 64 years, were
      examined in acute and long-term periods of the brain injury of moderate severity.
      An open, comparative, randomized study was performed before and after treatment
      with cerebrolysin. RESULTS AND CONCLUSION: Cognitive impairment, dysregulation
      type in the acute and long-term brain injury of mild to moderate severity was
      associated with the low content of brain-derived neurotrophic factor. These
      disorders were clinically more pronounced in patients with the damage of the
      frontal and temporal lobes. After treatment with cerebrolysin, a significant
      positive dynamics on the scale of frontal dysfunction and increased levels of
      serum brain-derived neurotrophic factor were identified.

PMID- 29171487
TI  - [Evaluation of efficiency and safety of adding neuromultivit to basic therapy of
      vertebrogenic radiculopathy].
AB  - AIM: To evaluate the efficacy and safety of neuromultivit (valiant, Russia) as
      add-on to the basic therapy of vertebrogenic radiculopathy (VR) L5-S1. MATERIAL
      AND METHODS: The open clinical trial included 100 patients with VR L5-S1
      randomized into 2 groups. In group 1, patients received neuromultivit and basic
      therapy; in group 2 only basic therapy. Treatment efficacy was assessed by the
      dynamics of regression of pain intensity on the visual analogue scale (VAS),
      McGill pain questionnaire (MGPQ), Aberdeen back pain scale (ABPS), the Quebec
      Back Pain Disability Scale (QBPDS), the dynamics of neurologic symptoms, the need
      for additional treatment with NSAID. Safety was assessed by evaluation of vital
      functions, laboratory tests, ECG, registration of adverse events (AE). RESULTS:
      In both groups, a significant positive changes on VAS, MGPQ, ABPS, QBPDS were
      observed. Nevertheless, the positive effect of therapy was more pronounced in
      group 1 p<0.05). The AE spectrum between two groups did not differ significantly
      (p<0.05). CONCLUSION: Addition of neuromultivit to basic therapy increased the
      efficacy of treatment of VR L5-S1.

PMID- 29171488
TI  - [The efficacy of recognan in the early stage of ischemic stroke].
AB  - AIM: To assess the efficacy and safety of recognan in patients with acute
      ischemic stroke (IS). MATERIAL AND METHODS: Seventy-nine patients, aged from 30
      to 80 years, were examined in the early stage of IS. All patients received
      recognan (citicoline) in dose of 1000 mg/daily during 15 days. The recovery of
      cognitive functions (MMSE), level of consciousness (Glasgow Coma Scale), severity
      of focal neurological deficit (NIHSS) and functional recovery (Rankin scale,
      Barthel index, Rivermead Mobility Index) were assessed. RESULTS AND CONCLUSION: A
      decrease of cognitive impairment, improvement of memory, regression of
      neurological symptoms and increase in the motor activity were observed. Recognan
      used in dose of 1000 mg/daily during 15 days in the complex treatment of patients
      with IS promotes the recovery of cognitive function, reduces neurological
      symptoms and improves the recovery of motor activity.

PMID- 29171489
TI  - [Melatonin in the treatment of low back pain and predictors of its efficacy].
AB  - AIM: To assess analgesic properties of melatonin in the treatment of chronic non
      specific low back pain and to study predictors of its efficacy. MATERIAL AND
      METHODS: A study included 178 patients, aged from 40 to 65 years, with chronic
      non-specific low back pain during >3 month and the VAS score >3. Patients were
      stratified into 6 groups (3 pairs of comparison). In the first pair, patients of
      both groups received a combination of 500 mg of glucosamine hydrochloride and 500
      mg of chondroitin sulfate; in the second pair - a combination of 500 mg of
      glucosamine hydrochloride and 500 mg of chondroitin sulfate and diclofenac, in
      the third pair - diclofenac. All patients received additionally melaxen. The
      duration of the study was 3 month in the first pair and one month in the second
      and third pairs. With regard to response to melatonin, patients of the main
      groups were divided into responders and non-responders. Baseline factors
      determining the efficacy of treatment with melatonin were studied. RESULTS AND
      CONCLUSION: A significant reduction in pain intensity at movement and resting
      state was noted in all main groups compared to comparison groups. This result
      indicates possible analgesic properties of melatonin. Moreover, factors
      predicting the efficacy of such therapy were determined. Addition of melatonin to
      the standard scheme of low back pain treatment increases its efficacy, in
      particular in case of comorbidity of pain and sleep disorders and depressive
      symptoms.

PMID- 29171490
TI  - [Genetic and clinical predictors of treatment efficacy in depressive disorders].
AB  - AIM: To study clinical and genetic characteristics that impact on the efficacy of
      pharmacotherapy of depressive disorders. MATERIAL AND METHODS: The study included
      188 patients with unipolar depressive disorders of different genesis
      (psychogenic, endogenous and organic). A clinical-psychopathological method and
      depression psychometric scales were used. Serotonin transporter 5-HTTLPR and
      STin2 and dopamine transporter 3',-VNTR polymorphisms were determined. RESULTS
      AND CONCLUSION: The S-allele of the 5-HTTLPR polymorphism is associated with the
      low efficacy of treatment with selective serotonin reuptake inhibitors. Tricyclic
      antidepressants are more effective in treatment of psychogenic depression. The
      authors determined clinical factors that can predict response to treatment of
      psychogenic and endogenous depression. No predictors were found for organic
      depression.

PMID- 29171491
TI  - [The efficacy and tolerability of pericyazine in the treatment of patients with
      schizotypal disorder, organic personality disorders and pathocharacterological
      changes within personality disorders].
AB  - AIM: To assess the efficacy and tolerability of pericyazine in the treatment of
      patients with mental disorders manifesting with psychopathic-like symptoms and
      correction of pathocharacterological disorders in patients with personality
      disorders during the short-term admission to the hospital or the long-term
      outpatient treatment. MATERIAL AND METHODS: Sixty-three patients with schizotypal
      personality disorder and organic personality disorder with psychopathic-like
      symptoms and pathocharacterological changes within the diagnosis of dissocial
      personality disorder and borderline personality disorder were examined. Patients
      received pericyazine during the short-term admission to the hospital (6 weeks) or
      the long-term outpatient treatment (6 month). Efficacy, tolerability and
      compliance were assessed in the study. RESULTS AND CONCLUSION: Treatment with
      pricyazine was effective in all patients. The improvement was seen in patients
      with organic personality disorders and patients with personality disorders
      (psychopathy). The maximal effect was observed in inpatients and this effect
      remained during outpatient treatment. The improvement of mental state of patients
      with schizotypal personality disorder achieved during inpatient treatment with
      pericyazine continued during the long-term outpatient treatment. Side-effects
      were restricted to extrapyramidal symptoms, the frequency of metabolic syndrome
      was low. During outpatient treatment, the compliance was higher if the patient
      was managed by the same psychiatrist during inpatient- and outpatient treatment.

PMID- 29171492
TI  - [Brainstem auditory evoked potentials in neurophysiological assessment of brain
      stem dysfunction in patients with atherostenosis of vertebral arteries].
AB  - AIM: To assess brain stem dysfunction in patients with hemodynamically
      significant stenosis of vertebral arteries (VA) using short latency brainstem
      auditory evoked potentials (BAEP). MATERIAL AND METHODS: The study group included
      50 patients (mean age 64+/-6 years) with hemodynamically significant extracranial
      VA stenosis. RESULTS: Patients with hemodynamically significant extracranial VA
      stenosis had BAEP abnormalities including the elongation of interpeak intervals I
      V and peak V latency as well as the reduction of peak I amplitude. After
      transluminal balloon angioplasty with stenting of VA stenoses, there was a
      shortening of peak V latency compared to the preoperative period that reflected
      the improvement of brain stem conductive functions. CONCLUSION: Atherostenosis of
      vertebral arteries is characterized by the signs of brain stem dysfunction,
      predominantly in the pontomesencephal brain stem. After transluminal balloon
      angioplasty with stenting of VA, the improvement of brain stem conductive
      functions was observed.

PMID- 29171493
TI  - [Epigenetic research of cognitive deficit in schizophrenia: some methodological
      considerations].
AB  - AIM: To highlights the problems of assessing cognitive deficits in schizophrenia,
      relevant to the epigenetic, as well as a wide range of other approaches to the
      search for biological bases of cognition. MATERIAL AND METHODS: The literature on
      the weaknesses in the evaluation of cognitive functions in patients with
      schizophrenia are summarized and discussed. The analysis is illustrated by our
      experience in developing a cognitive battery and a sample to examine
      relationships between DNA methylation in blood cells and cognitive deficits in
      schizophrenia. RESULTS AND CONCLUSION: It has been shown that to assess cognitive
      deficits in patients and to reduce the influence of confounders in epigenetic
      analysis it is necessary (1) to use a battery with the existing co-normative data
      in the target population, which allows to evaluate representativeness of control
      and patients included in the study sample, (2) to verify the theoretically driven
      battery structure using normative population and a cohort of patients, (3) to
      balance groups of cases and controls on the number, age and sex, for which an
      individual matching of cases and controls is best suited, (4) to conduct an
      additional statistical analysis controlling for education and smoking.

PMID- 29171494
TI  - [The clinical features of Parkinson's disease in patients with mutations and
      polymorphic variants of GBA gene].
AB  - BACKGROUND: Mutations in the glucocerebrosidase gene (GBA) increase the risk of
      Parkinson's disease (PD) by 6-10 times in all populations and are associated with
      the early-onset of PD, development of cognitive impairment and presence of
      psychotic disorders. At the same time, polymorphic variants associated with the
      twofold increase in the risk of PD were also described in the GBA gene. AIM: To
      estimate the clinical features of PD in patients with mutations and polymorphic
      variants of the GBA gene. MATERIAL AND METHODS: Evaluation of motor, cognitive,
      emotional, psychotic and autonomic dysfunctions in patients with mutations
      (N370S, L444P) and polymorphic variants (E326K, T369M) in the GBA gene was
      performed using clinical scales. RESULTS: Patients with mutations (mGBA-PD), and
      with polymorphic variants (pGBA-PD) in the GBA gene were compared with the group
      of patients with sporadic PD (sPD). Compared to sPD, affective disorders
      (depression and anxiety) were more expressed in the mGBA-PD group (p=0.001) and
      the general GBA-PD group (p=0.001) assessed with Sheehan anxiety rating scale, in
      the pGBA-PD group (p=0.012) and the general GBA-PD group (p=0.05) assessed with
      the NPI, in the mGBA-PD (p=0.003), pGBA-PD (p=0.022), and general GBA-PD groups
      (p=0.001) assessed with the Hospital Anxiety and Depression scale (HADS 'A'), and
      in the pGBA-PD group (p=0.005) assessed with the HADS 'D'. Non-motor symptoms
      assessed with the PD-NMS were more expressed in the pGBA-PD patients (p=0.007)
      and in the total group with GBA-PD (p=0,014) compared to sPD. Cognitive
      impairment measured with MMSE was more marked in mGBA-PD patients (p=0.022).
      Differences in motor and non-motor clinical symptoms between pGBA-PD and mGBA-PD
      groups were not found. CONCLUSION: Thus, clinical features of non-motor symptoms
      were described both in carriers of GBA mutations and polymorphisms.
      Identification of the specific clinical phenotype of PD in carriers of GBA
      polymorphic variants is important due to their relatively high prevalence in PD
      patients.

PMID- 29171495
TI  - [Mexidol effect on the factor induced by hypoxia HIF-1alpha expression in the rat
      cerebral cortex in ischemia].
AB  - : The aim of the research - to study the Mexidol (ethylmethylhydroxypyridine
      succinate) effect on the factor induced by hypoxia (HIF-1alpha) expression in the
      frontal cortex of the brain in its ischemia. MATERIAL AND METHODS: The work was
      performed on the 64 male Wistar rats. The expression of HIF-1alpha was determined
      immunohistochemically. RESULTS AND DISCUSSION: It is determined that single
      intraperitoneal administration of Mexidol at a dose 120 mg/kg and oral
      administration at a dose 100 mg/kg three times a day for 14 days is not affected
      the expression of HIF-1alpha. Unilateral occlusion of the common carotid artery
      increases the expression of HIF-1alpha at 4 hours after the occlusion. Oral
      administration of Mexidol at a dose 100 mg/kg three times a day for 14 days
      before and after ischemia increases the expression of HIF-1alpha after 4 and 12
      hours in comparison with the norm, on the 5th day in comparison with occlusion
      control. Thus, it has been established that Mexidol increases the expression of
      HIF-1alpha in the frontal cortex of rat brain not under normal conditions, but in
      unilateral occlusion of the common carotid artery.

PMID- 29171496
TI  - [Zero citation of Russian institute publications on the psychiatry and
      addiction].
AB  - AIM: To evaluate the zero-citation sizes. MATERIAL AND METHODS: Based on the data
      of the Russian Science Citation Index the publication activity of four leading
      institutes in the field of Psychiatry and Addiction is analyzed. The same indices
      in the field of Neurology were used as a control. Number and percentage of
      publications with >=1 citations and zero-citation were analyzed. RESULTS: It has
      been shown that in psychiatric science zero citation rate is quite high (from
      32.8% to 47.2%, an average of 42.9%). It is higher compared to the control.
      CONCLUSION: Zero-citation indicator is essential to evaluate the effectiveness of
      scientific institutions.

PMID- 29171497
TI  - [The optimization of restoration approaches of advanced hand activity using the
      sensorial glove and the mCIMT method].
AB  - AIM: To reason the choice of methods of restoration of advanced hand activity
      depending on severity of motor disturbance in the top extremity. MATERIAL AND
      METHODS: Eighty-eight patients were randomized into 3 groups: 1) the mCIMT group,
      2) the 'touch glove' group, 3) the control group. For assessment of physical
      activity of the top extremity Fugl-Meyer Assessment Upper Extremity, Nine-Hole
      Peg Test, Motor Assessment Scale were used. Assessment of non-use phenomenon was
      carried out with the Motor Activity Log scale. RESULTS AND CONCLUSION: At a stage
      of severe motor dysfunction, there was a restoration of proximal departments of a
      hand in all groups, neither method was superior to the other. In case of moderate
      severity of motor deficiency of the upper extremity the most effective was the
      method based on the principle of biological feedback - 'a touch glove'. In the
      group with mild severity of motor dysfunction, the best recovery was achieved in
      the mCIMT group.

PMID- 29171498
TI  - [Temporomandibular disorder as the most prevalent cause of facial pain: current
      evidence].
AB  - Orofacial pain is a comprehensive and multi-faceted syndrome. After dental causes
      have been excluded, neurologists are challenged to diagnose the cause of pain.
      The paper gives a detailed review of one of the most common causes of facial pain
      - temporomandibular disorder (TMD). Current DC/TMD diagnostic criteria, patient
      examination protocols and a new perspective on TMD pathophysiology based on the
      recent neurological studies are presented. The article also discusses modern
      approaches to TMD management.

PMID- 29171499
TI  - [Treatment of spasticity after traumatic brain injury in children: the role of
      botulinum toxin therapy].
AB  - Traumatic brain injury (TBI) is one of the main reasons of death and disability
      in children and adolescents in Russia and abroad. Spasticity is a frequent
      outcome of the TBI that influences on the rehabilitation prognosis, degree of
      movement disorders and quality of life after trauma. Early spasticity correction
      and complex rehabilitation lead to the optimal recovery and prevent secondary
      complications. This review presents the current data about the prognostic role of
      the spasticity in children after TBI, methods of its correction and their
      scientific evidence. Limitations and challenges of per-oral antispastic agents
      are described especially for the patients with local spasticity. Attention is
      focused on the methods of treatment of local hypertonus, in particular botulinum
      toxin A (BTA) injections proved to be effective in adults with acquired brain
      injury. The article summarizes the results of international investigations,
      systematic reviews and consensus statements about the efficacy and safety of
      botulinum toxin treatment in children after the TBI. The authors describe an
      algorithm of the optimal patient selection and goal setting for BTA injections in
      children with acquired brain injury.

PMID- 29171500
TI  - [Endothelium as a target for new therapeutic strategies in cerebral vascular
      diseases].
AB  - The author evaluates a role of endothelium in the pathogenesis of cerebral
      vascular diseases (CVD) and considers the concept about endothelium as prevention
      and treatment of pathological processes leading to or triggering CVD. There are
      two medical strategies for correction of endothelium dysfunction in CVD: tactic
      (using of antioxidants) and strategic (statins, hypotensive drugs,
      antiaggregants).

PMID- 29171501
TI  - [Nitric oxide: from the mechanism of action to pharmacological effects in
      cerebrovascular diseases].
AB  - The article presents the data of studies of nitric oxide (NO) in the pathogenesis
      of cerebrovascular diseases. It is emphasized that endothelial dysfunction
      contributes to the formation of cerebrovascular diseases. Generalized data on
      preparations with endothelioprotective effect, as well as own data on the use of
      the preparation 'Divaza' in patients of middle and advanced age with chronic
      cerebrovascular disease are given.

PMID- 29171502
TI  - [Memantine: from the original brand to generics].
AB  - Memantine is the first clinically available glutamate antagonist, with an
      antagonist action at the N-methyl-D-aspartate receptors in the brain, for
      correction of cognitive and behavioral functions in neurodegenerative disorders.
      Glutamate mediated excitotoxic neuronal damage has been implicated in Alzheimer's
      disease (AD) and other parkinsonism-related dementias and, therefore, memantine
      represents a novel mode of action to counteract the glutamate-mediated
      excitotoxicity. In moderate to severe AD, 20 mg of memantine shows a positive
      effect on cognition, mood, behavior and the ability to perform activities of
      daily living. Long-term studies show good tolerability of memantine with an
      acceptable side-effect profile. In recent years, there have been a proliferation
      of a number of companies producing generic memantine with different trade names.
      In Russia, the first memantine generic drug noojerone was approved in 2010 and
      its use has since been supported by a growing evidence base of efficacy in real
      life clinical practice. Postmarketing studies show that noojerone provides long
      term and effective therapy in patients with moderate and severe Alzheimer's
      dementia. This observation is supported by the clinically significant therapeutic
      effect of noojerone on cognitive and daily functioning, behavioral and psychotic
      symptoms of dementia and a reduction of the burden on caregivers. This generic
      version of memantine is affordable and, therefore, reduces financial burden on
      patients and improves compliance with treatment.

PMID- 29171503
TI  - [Prevention and treatment of hepatic encephalopathy].
AB  - Hepatic encephalopathy is a common neuropsychiatric complication of serious liver
      diseases and serves as a marker for worsening of their course and increasing the
      risk of death. The principal pathogenesis factors of hepatic encephalopathy is
      the excessive formation of ammonia and its accumulation by astrocytes. A key role
      in the prevention and treatment of hepatic encephalopathy is played by drugs that
      prevent hyperammonemia and promote the removal of ammonia from the body, namely
      lactulose, rifaximin and L-ornithine-L-aspartate. L-ornithine-L-aspartate has
      proven clinical effectiveness in the treatment of hepatic encephalopathy,
      prevents the transformation of minimal hepatic encephalopathy into overt forms,
      increases the tolerability of psychotropic drugs used in the treatment of alcohol
      dependence, and improves cognitive functions.

PMID- 29171504
TI  - Intraoperative optical coherence tomography to evaluate the effect of the eyelid
      speculum on corneal pachymetry during accelerated corneal cross-linking (9
      mW/cm2).
AB  - PurposeTo investigate intraoperative anterior segment optical coherence
      tomography (AS-OCT) to compare pachymetry changes between two methods (group 1:
      speculum-on, group 2: speculum-off during riboflavin instillation stage) during
      corneal cross-linking /CXL) (9 mW/cm2 for 10 min) in keratoconic
      patients.MethodsIn this interventional case series, 11 eyes (11 patients) in
      group 1 and 14 eyes (14 patients) in group 2 were enrolled. Pachymetry
      measurements by spectral domain OCT was performed at baseline, after epithelial
      removal, after 30 min of imbibition with riboflavin, and after UV irradiation.
      Repeated measures analysis of variance was used to compare the trend of changes
      in different stages of the procedure within and between two groups.ResultsThe
      corneal thinnest pachymerty (CTP) at baseline, after epithelial removal, 30 min
      of riboflavin instillation, and irradiation was 469.8+/-26.5, 438.0+/-27.1,
      354.3+/-28.4, 367.1+/-31.8 microns in group 1 and 463.2+/-25.1, 438.0+/-27.1,
      421.6+/-54.0, 386.9+/-34.0 microns in group 2, respectively. Group 1 showed a
      significantly greater decrease in the corneal pachymetry (P<0.001) during
      riboflavin instillation, while in group 2 a greater decrease in CTP was observed
      during the UV irradiation phase (P=0.002).ConclusionsUsing the intraoperative
      OCT, the speculum-off group had a more stable corneal pachymetry during
      riboflavin instillation time. Despite this, the effect was not lasting throughout
      the procedure; significant changes were noted in the corneal pachymetry at the
      end of operation in both groups; further highlighting the limitations imposed by
      corneal stromal shrinkage using isotonic dextran containing riboflavin solution
      for CXL.

PMID- 29171505
TI  - Comment on: 'Corneal confocal scanning laser microscopy in patients with dry eye
      disease treated with topical cyclosporine'.

PMID- 29171507
TI  - Reply to Comment on: 'Corneal confocal scanning laser microscopy in patients with
      dry eye disease treated with topical cyclosporine'.

PMID- 29171509
TI  - Restorative dentistry: An innovative handling approach.

PMID- 29171506
TI  - Inflammasomes, the eye and anti-inflammasome therapy.
AB  - Inflammasomes, key molecular regulators that play an important role in
      inflammation, consist of a central protein, an adaptor protein ASC (apoptosis
      speck-like protein) and a caspase-1 protein. Upon activation, caspase-1 induces
      maturation of cytokines such as interleukin-1beta (IL-1beta) and interleukin-18
      (IL-18). The release of these cytokines can result in inflammation. Inflammasomes
      are activated by a variety of factors and their activation involves complex
      signalling leading to resolution of infection, but can also contribute to the
      pathology of inflammatory, autoimmune, and infectious diseases. The role of
      NLRP1, NLRP3, NLRC4 and AIM2 inflammasomes in the pathogenesis of ocular diseases
      such as glaucoma, age related macular degeneration (AMD), diabetic retinopathy,
      dry eye and infections of the eye has been established over the past decade. In
      experimental studies and models, inhibition of inflammasomes generally helps to
      reduce the inflammation associated with these eye diseases, but as yet the role
      of these inflammasomes in many human eye diseases is unknown. Therefore, a need
      exists to study and understand various aspects of inflammasomes and their
      contribution to the pathology of human eye diseases. The goal of this review is
      to discuss the role of inflammasomes in the pathology of eye diseases, scope for
      anti-inflammasome therapy, and current research gaps in inflammasome-related eye
      disease.

PMID- 29171510
TI  - Clinical examination & record-keeping: Part 1: Dental records.
AB  - This article forms part of a BDJ series of Practice papers on the subject of
      clinical examination and related record keeping. The series is taken from the
      Faculty of General Dental Practice UK (FGDP[UK]) 2016 Good Practice Guidelines
      book on this topic, edited by A. M. Hadden. This particular article, the first in
      the series, describes what constitutes dental records. The principles are
      applicable to electronic and handwritten records. Records will fall below
      acceptable standards when it is not clear to another clinician what was found,
      planned, discussed, and what treatment carried out.

PMID- 29171511
TI  - Defensive dentistry and the young dentist - this isn't what we signed up for.
AB  - Why did I want to become a dentist? I wanted a job where I would be respected as
      a professional and could change the lives of others, using my hands. This, I
      thought, would be my ideal profession; one where I could walk into work with a
      smile on my face every day. Cue dental school a place where one is trained to
      become competent in all areas of general dentistry. As readers will appreciate,
      dentistry is a vast field and the question that comes to mind is how so many
      diverse and varied topics can be jam packed into a five-year course. There has
      always been a debate about what to put in, and therefore leave out. At my
      particular dental school, the first two years covered basic scientific theory,
      leaving three years to get into clinical dentistry with some 'other' aspects
      sprinkled in. Some of these aspects included general communication skills, record
      keeping and one or two practice visits at fancy dental practices to see how good
      life was as a general dental practitioner. In light of the profession's current
      climate and the rise of defensive dentistry, I aim to reflect on why many young
      graduates from all over the country feel out of touch with the profession so
      early on in their careers, and why some of these 'other' aspects of dentistry
      should have been covered much more comprehensively to prepare us for the big wide
      world.

PMID- 29171512
TI  - Personal account: The dentist on a warship.

PMID- 29171513
TI  - Anaesthesia: A sense of balance.

PMID- 29171514
TI  - Oral surgery II: Part 4. Common oral lesions.
AB  - Lesions of the mouth are surprisingly common and vary from the totally innocuous
      to highly malignant neoplasms. As required for the management of all patients, a
      clear and concise history and a thorough clinical examination are essential. In
      addition, radiographs and other laboratory investigations may be required to
      formulate a differential diagnosis. A definitive diagnosis, on which treatment
      planning should always be based, can usually only be confirmed following a
      histological examination. This may be obtained through a biopsy or following
      total excision of a lesion.

PMID- 29171518
TI  - Help ease festive hardship among dentists and their families.

PMID- 29171515
TI  - Dental education: Microteaching.

PMID- 29171516
TI  - Upper anterior tooth dimensions in a young-adult Indian population in the UK:
      implications for aesthetic dentistry.
AB  - Introduction Knowledge of tooth dimensions and relationships and ethnic
      variations in these parameters are important in the planning and provision of
      aesthetic dentistry.Aim The aim of the present study was to investigate the
      dimensions and relationships of the upper anterior teeth in young adults of
      Indian origin, living in an urban location in the UK, and to compare the data
      obtained with data pertaining to other ethnic groups.Materials and methods This
      was a qualitative, non-experimental, cross sectional descriptive study with
      ethical approval. The dependent variables were tooth dimensions and
      relationships. The independent variable was gender. Fifty male and 50 female
      young adult Indians were recruited to the study, according to predetermined
      criteria. Upper and lower, full arch impressions were obtained for each of the
      100 participants. Stone cast were obtained from these impressions. The width and
      length of each upper anterior tooth included in the casts were measured using
      precision callipers. Anterior arch length was determined using a flexible
      measuring tape. All measurements were repeated at least three times to obtain
      consistent values. The error of the method was investigated by means of repeat
      measurements. The data obtained was analysed, and compared with existing data on
      tooth dimensions and used to investigate the presence of Golden Proportion
      relationships.Results The measurements obtained had a normal distribution.
      Statistical analysis revealed significant differences in the overall data for
      left and right canine width and length (P <0.05). No such differences were noted
      in respect of the upper central and lateral incisors. Also, significant
      differences (P <0.05) were found to exist between male and female subjects in
      respect of the width of all anterior tooth types, except for the upper right
      lateral incisor. There were significant differences in the length of the upper
      left central incisor and upper right and left canines between male and female
      subjects (P <0.05). Significant differences (<0.05) were found in the width to
      length ratios between right and left canines. No such differences were observed
      for incisors. There was an absence of Golden Proportion relationships.Conclusion
      Within the limitations of the present study, it is concluded that it is
      inappropriate to adopt a formulaic, left/right symmetrical approach to smile
      design in the provision of aesthetic dentistry for young adults of Indian origin.

PMID- 29171519
TI  - Startling lack of awareness of HPV-mouth cancer link.

PMID- 29171520
TI  - Let them drink water.

PMID- 29171522
TI  - Oral health: Ever increasing pressures.

PMID- 29171526
TI  - Starting Well Programme launched in Middlesbrough.

PMID- 29171527
TI  - Peri-implantitis - the patient perspective: Patient-centred perspectives and
      understanding of peri-implantitis.
AB  - Patients have a poor understanding of peri-implantitis so it is important to
      educate them to help prevent this condition, which negatively impacts on quality
      of life.

PMID- 29171529
TI  - Long-term follow up of implant therapy: Occurrence of cases with peri-implant
      mucositis or peri-implantitis in a 21-26-year follow-up study.
AB  - Regular supportive care should be emphasised for all patients but individuals who
      present with multiple implants and/or peri-implant mucositis should receive
      special clinical attention.

PMID- 29171530
TI  - Listening and shouting.

PMID- 29171531
TI  - Teeth as pearls of wisdom.
AB  - The role of teeth as lifestyle indicators of the past and present, and as key
      elements of evolutionary and forensic studies is explored. The wisdom of
      entrenched information in the structure of enamel, dentine and the DNA of dental
      pulp cells is being extracted by new technologies.

PMID- 29171533
TI  - Foundation training alternative.

PMID- 29171534
TI  - Greater Manchester schools and nurseries set to improve dental care.

PMID- 29171538
TI  - Jennifer Mary Nawarska (nee O'Brien) and Stanislaw Robert Wlosok Nawarski.

PMID- 29171537
TI  - Peri-implant maintenance therapy: Association of preventive maintenance therapy
      compliance and peri-implant disease: A cross-sectional study.
AB  - Peri-implant maintenance compliance at least twice a year appears to be crucial
      in preventing peri-implantitis.

PMID- 29171539
TI  - BRIGHT brushing initiative receives L1.9 million.

PMID- 29171541
TI  - Patient safety: Swallowed objects.

PMID- 29171543
TI  - State-sponsored dental terrorism?
AB  - Has the state's manipulation of the NHS dental contract systems deliberately, or
      accidentally, had corrupting effects on the behaviours of some members of the
      dental profession? If the answer is 'possibly' or 'probably', then obvious
      questions that follow include, 'was this done deliberately' and if so, 'why'?
      Could this have been done for largely altruistic reasons, or was it done to
      achieve government control for minimum cost? Might this have been undertaken for
      political, financial or ideological reasons - regardless of any adverse longer
      term consequences for some patients or for some dental professionals? Might it
      have been done to take greater control of the dental profession on the grounds
      that all professions are a conspiracy against the laity, as the mildly paranoid
      George Bernard Shaw once alleged? Is it possible that some of this manipulation
      might have been done to help to disempower yet another profession, allegedly to
      'modernise it', but perhaps to enslave it for its own reasons? Was this just
      another example of some statist politicians wanting to interfere in all aspects
      of UK society, regardless of their lack of specific understanding, or any proven
      expertise, in many areas? Could the state's manipulation of contracts and
      processes be regarded as an abuse of power by a virtual monopoly, which has been
      used to control a largely altruistic profession by imposing corrupting NHS dental
      contract systems with the most recent one involving 'units of dental activity'
      (UDAs)? Perhaps it was really about some politicians wanting ever more power,
      control or money - their usual drivers - with the dental and medical professions
      accidentally becoming casualties?

PMID- 29171545
TI  - Alternative sugars: Coconut sugar.

PMID- 29171547
TI  - A dentist's life: Practising in the Peak District.

PMID- 29171551
TI  - Women and Diabetes: They have a right to a healthy future!

PMID- 29171550
TI  - Health effect of chronic exposure to carbon disulfide (C2) on women employed in
      viscose industry.
AB  - Many women are exposed to carbon disulfide (C2) hazards at work every day.
      Working with C2 may cause some women to experience abnormalities in their
      reproductive health. Until now obtained data is generally concentrated on the
      health effects of C2 observed in the viscose industry. To date, C2 has not been
      studied precisely for its potential to have damaging effects on female
      reproductive system, especially the frequency of menstrual disturbances and the
      course of menopause. The aim of the study was to sum up female reproductive
      health hazards amongst women chronically exposed to C2 in their workplace in the
      viscose industry. In order to study the effect of C2 in the contemporary viscose
      industry, exposure measurements should be collected in prospective or cross
      sectional studies. In conclusion, reproductive health hazards for women
      chronically exposed to C2 in the workplace in the viscose industry are the
      following: 1) menstrual disorders essentially are more frequent than in the case
      of the healthy women, 2) for women chronically exposed to C2 the average
      menopausal age is statistically earlier, as compared to healthy women, 3) complex
      disturbances in neurohormonal system for women exposed to C2, resulting from
      toxic influences of C2, which cause the secretion of estrogens and progesterone
      in ovaries and dehydroepiandrosterone sulfate in the adrenal gland to diminish.
      Med Pr 2018;69(3):329-335.

PMID- 29171552
TI  - The challenge of dealing with animal derived ingredients in medical/surgical
      products.

PMID- 29171553
TI  - Negative correlation among vitamin B12 levels, obesity severity and metabolic
      syndrome in obese children: A case control study.
AB  - OBJECTIVE: To determine the relationship among vitamin B12 status, obesity
      severity, and metabolic syndrome and its components in obese children.. METHODS:
      This case-control study was conducted at the School of Medicine, Gaziosmanpasa
      University, Tokat, Turkey, from January 2012 and October 2014, and comprised
      cases of obese and healthy children. The obese children were divided into three
      groups according to body mass index-standard deviation score quartiles. Group 1
      included the first quartile, group 2 included the second and third quartiles, and
      group 3 included the fourth quartile. Patients with a body mass index of >95th
      percentile, according to reference curves for Turkish children and adolescents,
      were considered obese.Patients with a body mass index between15th and 85th
      percentile were considered to have normal weight. The World Health Organisation's
      modified metabolic syndrome criteria for children were used to diagnose metabolic
      syndrome.SPSS 19 was used for data analysis. RESULTS: Of the 256 participants,
      153(59.8%) were obese and 103(40.2%) were healthy controls. The mean age of the
      obese children was 12.69+/-2.29 years and that of healthy controls was 13.05+/
      2.48 years. Mean vitamin B12 levels were significantly lower among obese children
      than healthy volunteers (p<0.001). Age and body mass index-standard deviation
      score were significantly associated with vitamin B12 status (r= -0.175, p=0.030;
      r= -0.210, p=0.09, respectively). CONCLUSIONS: Increase in body mass index
      standard deviation score was associated with a decrease in vitamin B12 levels.

PMID- 29171554
TI  - Evaluation of several classification methods in carpal tunnel syndrome.
AB  - OBJECTIVE: To investigate the performance and effectiveness of 4 classification
      methods including support vector machine, naive Bayes, classification tree, and
      artificial neural network in the detection of carpal tunnel syndrome. METHODS:
      This retrospective study was conducted at Yuzuncu Yil University, Van, Turkey,
      and comprised record of patients suspected of having carpal tunnel syndrome
      between January and December 2013. The evaluations included age, gender, and 6
      electromyography variables, including right/left median nerve sensory velocity,
      right/left fourth finger peak latency difference, and right/left median nerve
      motor distal latency. We investigated the performance of classification methods
      such as support vector machine, naive Bayes, classification tree and artificial
      neural network in the patients using data obtained from electromyography scan. A
      total of 6 criteria were used for the assessment of performance, including: true
      positive rate, false positive rate, true negative rate, false negative rate,
      accuracy, and preciseness. RESULTS: Of the 109 patients, 88(80.7%) were women and
      21(19.3%) men. Besides, 67(61.5%) participants had carpal tunnel syndrome and
      42(38.5%) did not have it. On classification tree, only 2 variables, i.e. left
      fourth finger peak latency difference and right/left median nerve sensory
      velocity, were found to be statistically significant (p<0.001). Naive Bayes had
      the highest detection score (91.04%), followed by support vector machine
      (89.55%). CONCLUSIONS: Naive Bayes yielded better performance than all the other
      methods in the diagnosis of carpal tunnel syndrome, followed by support vector
      machine.

PMID- 29171555
TI  - Association of Vitamin D binding protein polymorphism with risk of type 2
      diabetes mellitus in a Pakistani urban population: A case control study.
AB  - OBJECTIVE: To assess if genotypes/diplotypes of vitamin D binding protein have
      any association with type 2 diabetes mellitus. METHODS: This case-control study
      was conducted from January 2013 to July 2015 at the endocrinology clinics of the
      Aga Khan University Hospital, Karachi, and comprised adult patients with type 2
      diabetes and their age- and gender-matched healthy controls. Venous blood was
      obtained and assessed for serum/plasma 25 hydroxyvitamin D, parathyroid hormone,
      calcium, alkaline phosphatase and creatinine. Deoxyribonucleic acid was isolated
      and genotyping was done by polymerase chain reaction-restriction fragment length
      polymorphism procedures. RESULTS: Of the 330 participants, there were 165(50%)
      cases and as many controls. There were 116(70.3%) males and 49(29.7%) females in
      each group. The mean age of the patients was 48.82+/-9.23 years and that of the
      controls was 46.27+/-8.77 years (range: 22-70 years) (p=0.010) Mean serum
      concentration of 25 hydroxy vitamin D was significantly higher among the patients
      compared to the controls (p<0.001), but not significantly different by genotypes
      or diplotypes (p>0.05). Multiple conditional logistic regression revealed an
      association of group-specific 1-2 genotype with patients when adjusted for age,
      body mass index, and serum levels of 25 hydroxy vitamin D with matched adjusted
      odds ratio (95% confidence interval) being 3.1(1.22-7.88). CONCLUSIONS: Group
      specific 1-2 genotype of vitamin D binding protein gene was associated with the
      risk of type 2 diabetes.

PMID- 29171556
TI  - Assessment of the risk factors of hypertension among adult & elderly group in
      twin cities of Pakistan.
AB  - OBJECTIVE: To estimate the prevalence of hypertension and to explore the risk
      factors associated with it. METHODS: In a cross-sectional study, a population
      based survey was conducted on inhabitants of Rawalpindi-Islamabad region, 219
      individuals; aged 18 years or above were included in the study. Blood pressure
      was measured along with information about individual's demographic and socio
      economic characteristics were obtained using a standard questionnaire.. RESULTS:
      Overall prevalence of hypertension was 29.22% (males: 21.9% and females: 78.1%)
      in individuals residing in Rawalpindi-Islamabad. High blood pressure is more
      associated with obesity (59.4%) and a progressive increase in hypertension was
      observed with increasing age. Bivariate analysis revealed that hypertension has a
      significant correlation (p-value<0.05) with age, gender, family status, weight
      and physical health. CONCLUSIONS: The study concludes that our generation is well
      aware about the risks and consequences of hypertension, but they still continue
      to make no or little effort in managing or preventing it. The factors
      contributing to hypertension are low physical activity, diet and lack of interest
      to maintain their health.

PMID- 29171557
TI  - Effects of supervised structured aerobic exercise training programme on level of
      Exertion, dyspnoea, VO2 max and Body Mass Index in patients with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To determine the effects of supervised structured aerobic exercise
      training programme on level of exertion, dyspnoea, maximum oxygen consumption,
      and body mass index in type 2 diabetics. METHODS: The randomised, controlled
      trial was carried out at Riphah Rehabilitation and Research Centre, Islamic
      International medical College Trust, Pakistan Railways General Hospital,
      Rawalpindi, Pakistan, from January 2015 to June 2016, and comprised type 2
      diabetics. Sedentary individuals of both genders, aged40-70 years, diagnosed on
      World Health Organisation's criteria were included. Participants were randomly
      divided into two groups, i.e. A (experimental) and B (control), by toss and trial
      method. Intervention in the experimental group were supervised structured aerobic
      exercise training programme, routine medication and dietary, while the control
      group was treated by routine medication and dietary plan for 25 weeks at 3 days
      per week for both groups. Level of exertion, dyspnoea, maximum oxygen consumption
      and body mass index were assessed and documented at baseline (0 week) and at the
      completion of intervention (after 25 weeks). SPSS20 was used for data analysis.
      RESULTS: Of the 102 participants, there were 51(50%) in each group. Pre- and post
      intervention analysis showed that a 25-week training programme, routine
      medication, and dietary plan significantly improved level of exertion, dyspnoea,
      maximum oxygen consumption and body mass index (p<0.05)) in the experimental
      group compared to the control group treated with routine medication, and dietary
      plan. CONCLUSIONS: The supervised structured aerobic exercise training programme
      along with routine medication and dietary plan positively influenced level of
      exertion, dyspnoea, maximum oxygen consumption and body mass index than routine
      medication and dietary plan in patients with type 2 diabetes.

PMID- 29171558
TI  - Enhanced recovery after surgery (ERAS) protocol in stoma reversals.
AB  - OBJECTIVE: To compare the length of hospital stay and return of bowel movement
      using the conventional management versus 'enhanced recovery after surgery'
      protocol. METHODS: This study was conducted at the Civil Hospital, Karachi, from
      June 2014 to May 2015, and comprised patients undergoing stoma reversal. Patients
      were randomly allocated in two equal groups, i.e. A (treated with conventional
      peri-operative management) and B (with 'enhanced recovery after surgery'
      protocol). Prolonged ileus, wound infection and length of hospital stay between
      the two groups were compared. SPSS 20 was used for statistical analysis. RESULTS:
      There were 60 participants who were divided into two groups of 30(50%) each.
      Overall, 39(65%) patients were males and 21(35%) were females. The mean age was
      27.80+/-9.99 years in group A and 23.87+/-4.56 years in group B. Besides, 25(83%)
      patients in group A had prolonged ileus compared to 3(10.7%) in group B (p=0.00).
      Moreover, 14(46.7%) patients in group A and 8(26.7%) patients in group B had
      wound infection (p=0.10). The mean duration of hospital stay was also less in
      group B compared to group A (p<0.05). CONCLUSIONS: The application of 'enhanced
      recovery after surgery' protocol was found to be safe.

PMID- 29171559
TI  - Prognostic importance of paraoxonase, arylesterase and mean platelet volume
      efficiency in acute ischaemic stroke.
AB  - OBJECTIVE: To study the prognostic importance activity of paraoxonase and
      arylesterase, and the value of mean platelet volume in patients with acute
      ischaemic stroke. METHODS: This case-control study was conducted at Harran
      University Hospital, Sanliurfa, Turkey, from January to June 2014, and comprised
      patients with symptoms of acute ischaemic stroke who presented to the emergency
      department. Paraoxonase activity, expressed in units per litre, or U/L, of serum,
      was evaluated in the absence of basal activity, and arylesterase activity was
      defined as micromoles, of phenol generated/min, and was expressed as U/L of
      serum. Mean platelet volume was measured as a routine parameter. SPSS 20 was used
      for data analysis. RESULTS: Of the 94 participants, 48(51%) were patients with
      acute ischaemic stroke and 46(49%) were control subjects. Moreover, 27(56.3%)
      patients were females and 21(43.7%) were males. In the control group, 26(56.5%)
      were females and 20(43.5%) were males. The mean age of patients was 68.39+/-11.83
      years compared to controls' 65+/-9.95 years. Decreased activity of prognostic
      importance and arylesterase were significant in patients than in the controls (p=
      0.016 and p= 0.001, respectively). The median platelets of patients was
      significantly lower than that of the controls (p=0.004). However, the median mean
      platelet volume values were similar in the both groups (p=0.568). Binary logistic
      regression analyses showed that the paraoxonase and arylesterase were risk
      markers for the patients. CONCLUSIONS: Decreased paraoxonase and arylesterase
      activity and decreased platelet counts were observed probably due to increased
      oxidative stress in acute ischaemic stroke patients.

PMID- 29171560
TI  - Mutation analysis for detection of drug resistance in mycobacterium tuberculosis
      isolates from Khyber Pakhtunkhwa, Pakistan.
AB  - OBJECTIVE: To examine the frequency and distribution of mutations in the 'hot
      spot regions' of drug-resistant genes. METHODS: The study was conducted at
      Provincial Tuberculosis Reference Laboratory, Peshawar, Pakistan, from April 2015
      to March 2016, and comprised sputum samples. Isolates were tested for drug
      susceptibility and resistant isolates were investigated for mutations analysis in
      the 'hot spot regions' of rpoB, rpsL, embB, pncA, gyrA and gyrB genes. RESULTS:
      Of the 163 isolates, 47(28.8%) isolates were resistant to streptomycin,
      56(34.36%) to rifampicin, 31(19%) to ethambutol, 16(9.82%) to pyrazinamide and
      59(36.2%) isolates were resistant to ofloxacin. Resistant isolates were randomly
      selected for mutation analysis. Moreover, 14(25%) rifampicin-resistant isolates
      were analyed for mutation in rpoB gene. Ser450Leu, Asp435Gly, Ser450Gln,
      Gly455Asp and Pro454His mutations were detected in the selected isolates.
      Furthermore, 16(34%) streptomycin-resistant isolates were analysed for mutation
      in rpsL gene. Lys43Arg, Lys88Arg and Lys111Ile mutations were detected in rpsL
      gene of 6(37.5%) isolates. Besides, 16(51.6%) ethambutol-resistant isolates were
      analysed for mutations in embB mutation; Ala281val, Met306Leu and Met306Val
      mutations were detected in 10(10(62.5%) isolates. Also, 8(50%) pyrazinamide
      resistant isolates were analysed for mutation in pncA gene. CONCLUSIONS: Some
      novel mutations were found in rpoB, rpsL and pncA genes.

PMID- 29171561
TI  - Frequency and pattern of common primary headache among depressed patients at
      tertiary care centre, Karachi.
AB  - OBJECTIVE: To determine the frequency of co-morbid common primary headaches among
      depressed patients. METHODS: This study was conducted at the Jinnah Postgraduate
      Medical Centre, Karachi, from July to December 2014, and comprised depressed
      patients. Diagnosis of depressive disorder was based on diagnostic criteria of
      International Classification of Diseases (10th version). For the diagnosis of
      common primary headaches, International Classification of Headache Disorders (2nd
      edition) criteria were applied. SPSS 17 was used for data analysis. RESULTS: Of
      the 331 participants, 129(39%) were males and 202(61%) were females. The overall
      mean age was 31.40+/-8.6 years (range: 18-50 years). Besides, 208(62.83%)
      participants had no headache and 123(37.16%) had common primary headaches. Of the
      latter, 18(5.4%) had migraine with aura, 49(14.8%) had migraine without aura and
      56(16.9%) had tension-type headache. Common primary headaches were more common in
      females and among those having severe depressive disorder. CONCLUSIONS: The
      primary headache was common among outpatients with depressive disorder,
      predominantly tension-type headache and migraine without aura.

PMID- 29171562
TI  - Frequency of acute kidney injury and its short-term effects after acute
      myocardial infarction.
AB  - OBJECTIVE: To find out the frequency of acute kidney injury and its short-term
      effects after acute myocardial infarction. METHODS: This descriptive, cross
      sectional study was conducted at the cardiology department of Lady Reading
      Hospital's Postgraduate Medical Institute, Peshawar, Pakistan, from January to
      June 2016, and comprised acute myocardial infarction patients. Non-probability
      consecutive sampling technique was used. SPSS 20 was used for data analysis.
      RESULTS: Of the 207 patients, 154(74.7%) were male and 53(25.6%) were female. The
      overall mean age was 59.09+/-8.6 years. At admission, the mean baseline
      creatinine was 0.97+/-0.23, the mean glomerular filtration rate was 83.30+/-25.4
      mL/min, and 30(14.4%) patients had an estimated glomerular filtration rate<60
      mL/min. Moreover, 43(20.7%) patients developed acute kidney injury. Post
      myocardial infarction in-hospital complications were higher in patients with
      acute kidney injury (p<0.05). CONCLUSIONS: In-hospital, short-term effects
      including acute heart failure, cardiogenic shock and arrhythmias were higher in
      acute kidney injury patients after acute myocardial infarction.

PMID- 29171563
TI  - The impact of health behaviours development training on healthy lifestyle
      behaviours amongst adolescents with obesity risk: A school example in a city in
      western Turkey.
AB  - OBJECTIVE: To determine the impact of health behaviours development training on
      healthy lifestyle. METHODS: This pre-experiment research was conducted at a
      junior high school governed by Aydin Provincial Directorate of National Education
      in Aydin, Turkey, from November 2014 to December 2015, and comprised students.
      All the students with obesity risk were included. Participants were asked to
      complete the questionnaire, and Healthy Lifestyle Behaviours Scale II.SPSS 18 was
      used for data analysis. RESULTS: Of the 1,042 students, 78(7.48%) were included
      in the study. Of them, 38(48.7%) were girls and 40(51.3%) were boys. The overall
      mean age was 11.77+/-0.92 years. It was found that healthy lifestyle behaviour
      improved after the training (p<0.05). CONCLUSIONS: Adolescents assessed with the
      Healthy Lifestyle Behaviour Scale II had higher post-training scores.

PMID- 29171564
TI  - Mental health of cardiac patients in Gilgit, Pakistan: A cross-sectional study.
AB  - OBJECTIVE: To assess and compare mental health of cardiac patients with disease
      free individuals. METHODS: This cross-sectional study was carried out at the
      Combined Military Hospital, Gilgit-Baltistan, Pakistan, from August to December
      2016, and comprised cardiac patients in group A and healthy controls in group B.
      Data was collected using mental health inventory, a 38-item tool to measure
      general psychological distress and well-being. Cardiac patients' mental health
      was compared with illness-free individuals by applying descriptive and
      inferential statistical techniques. SPSS 21 was used for data analysis. RESULTS:
      Of the 80 participants, 40(50%) were patients and the rest were controls. The
      mean mental health inventory score in group B was 150.72+/-19.94 compared to
      140.35+/-22.83in group A (p<0.05). Cardiac patients' mean score on psychological
      distress was 82.4+/-14.85 compared to 75.87+/-15.34in controls (p<0.05). The mean
      level of anxiety was 31.75+/-8.01 and that of depression was 14.58+/-3.58 in
      patients compared to 26.70+/-6.74 (p<0.01) and 12.65+/-4.34 (p<0.05) in the
      controls. CONCLUSIONS: Cardiac patients experienced higher level of depression
      and anxiety.

PMID- 29171565
TI  - Effectiveness of autism training programme: An example from Van, Turkey.
AB  - OBJECTIVE: To determine the knowledge and attitudes of family practitioners
      before and after their participation in a training programme. METHODS: The study
      was conducted at Van Training and Research Hospital, Van, Turkey, from December
      1to 15, 2016, and comprised family practitioners. Before the training, the
      practitioners were asked to fill out a questionnaire that was prepared by the
      researchers. Subsequently, the training course was presented by the child and
      adolescent psychiatrists. After the training, participants were asked to fill out
      the same questionnaire again. The results of survey were compared before and
      after training. Data was evaluated using SPSS 22.Descriptive analyses were used
      and baseline characteristics were compared between groups using McNemar's test
      and paired t-test. RESULTS: Of the 79 family practitioners who filled out the
      questionnaire,75(94.9%) were included. The mean age of the practitioners was
      28.2+/-11.63, with 40(53%) being females. Moreover,26(34.7%) participants thought
      that they had sufficient information regarding autism spectrum disorder before
      training, and this number increased to 66(88%) after training. There was a
      significant difference between pre-training and post-training scores of the
      questionnaire (p<0.001). CONCLUSIONS: There was a deficiency in knowledge about
      autism symptoms, aetiology, prevalence and treatment among family practitioners.
      .

PMID- 29171566
TI  - Knowledge and practices of critical care health professionals related to
      ventilator associated pneumonia in tertiary care hospitals of Islamabad and
      Rawalpindi.
AB  - OBJECTIVE: To assess knowledge and practices of critical care health
      professionals related to ventilator associated pneumonia. METHODS: This cross
      sectional survey was conducted at eight tertiary care public and private
      hospitals of Islamabad/Rawalpindi, Pakistan, from September 2015 to March 2016,
      and comprised healthcare professionals. Stratified random sampling was used. Data
      was collected using close-ended validated questionnaire. SPSS 22 was used for
      data analysis. RESULTS: Of the 153 participants, 45(29.4%) were doctors,
      91(59.4%) were nurses and 17(11.1%) were respiratory therapists. The overall mean
      age was 31+/-8.14 years. The overall mean knowledge and practice scores regarding
      prevention of ventilator-associated pneumonia were 11.14+/-3.12 and 8.83+/-1.53,
      respectively. The mean knowledge score was 11.77+/-3.84 for physicians, 10.84+/-
      2.91 for nurses and 10.82+/-1.94 for respiratory therapists. However, the best
      practice scores were seen in the respiratory therapists 9.64+/-0.78 (p=0.008).
      CONCLUSIONS: The majority of the participants had adequate knowledge and even
      better practices, particularly respiratory therapists.

PMID- 29171567
TI  - An effective and doable interventional strategy to enhance vaccination coverage -
      are we ready to change?
AB  - OBJECTIVE: To evaluate the effect of patient reminder calls on improvement of
      routine vaccination coverage. METHODS: This prospective, interventional study was
      conducted at Rawal Institute of Health Sciences, Islamabad, Pakistan, from
      December 2014 to August 2016, and comprised babies enrolled at the time of 1st
      vaccination. Babies who were given bacillus Calmette-Guerin, oral polio vaccine
      were included. Mobile phone numbers of parents were noted. The 1st reminder call
      was given after 7 days if a baby did not report on the scheduled date. Similarly,
      2nd and 3rd reminder calls were made after waiting for 7 days each time in case
      of non-reporting. Record of reporting and reminder calls was reviewed daily till
      all the enrolled babies crossed 15 months of age (scheduled time for 2nd dose of
      measles) plus 4 weeks. RESULTS: A total of 150 babies were enrolled at the time
      of 1st vaccination. Reporting without call within 01 week of scheduled date
      ranged from 52(34.66%) to 99(66%) for different vaccines. The 1st reminder call
      showed maximum improvement in reporting rate. The range of vaccination rate
      reached from 91(60.66%) to 132(88%). The 2nd call improved coverage rate range
      from 108(71.99%) to 140(93.33%). The 3rd call improved coverage rate from
      113(75.32%) to 144(96%). Overall coverage rate achieved ranged from 112.5(75%) to
      144(96%). CONCLUSIONS: Patient reminder calls showed significant effect in
      improvement of vaccination coverage rate of all antigens.

PMID- 29171568
TI  - Risk factors of cardiovascular disease and its recommendations in Pakistani
      context.
AB  - Cardiovascular diseases possess a major cause for fatality and disability the
      world over. Since last several decades, the rates of cardiovascular diseases
      related deaths have decreased in a number of high-income countries but increased
      in low- and middle-income countries with around 80% of the burden. Despite the
      seriousness of cardiovascular diseases in low- and middle-income countries,
      minimal attention is given to the prevention of cardiovascular diseases risk
      factors in South Asia, particularly in Pakistan. In addition, economic and
      political instability is accelerating the rates of cardiovascular diseases in the
      country. Practical efforts are required to enhance the understanding of
      cardiovascular diseases risk factors such as diet, physical activity, and tobacco
      control policies to support prevention and control at the population level. This
      paper reviews the major modifiable risk factors in Pakistan, highlights available
      preventive services, and presents the most likely ways to promote risk-factor
      reduction.

PMID- 29171569
TI  - HIV-1 in Pakistan: Where we stand? Where we will go?
AB  - Adherence to Islamic beliefs and being home to more than 190 million Muslims made
      many to believe that Pakistan was protected from human immunodeficiency virus or
      acquired immunodeficiency syndrome (HIV/AIDS). More than 30 years of HIV-1
      epidemic, the reality is totally different now. HIV/AIDS is not only becoming a
      major health concern of Pakistan, but also in several other Muslim-majority
      countries like Malaysia, Iran and Indonesia having prevalence rates of 0.4%, 0.2%
      and 0.3%, respectively. While in most parts of the world, HIV-1 infections have
      decreased or stabilised. However, the countries where HIV-1 prevalence is
      increased by 25-35% has Muslim majority. The high-risk populations in these
      countries are drug users and immoral sexual behaviours that include practices
      forbidden in Islam.

PMID- 29171570
TI  - Retinitis pigmentosa genes implicated in South Asian populations: a systematic
      review.
AB  - Retinitis pigmentosais one of the most prevalent causes of inherited retinal
      dystrophies worldwide. The widespread custom of consanguineous marriages in South
      Asian countries puts the population at risk for autosomal recessive disorders
      including retinitis pigmentosa. This systematic review was done between May and
      December 2015.A comprehensive literature search was carried out using MEDLINE and
      CINAHL databases and all relevant articles on causative mutations for non
      syndromic Retinitis pigmentosa from 1999 till 2015 were included. Overall, 41
      articles were identified involving 66 families; 28(68%)from Pakistan, 12(29%)
      from India and 1(2.4%) from Bangladesh. No data was available from the rest of
      countries in the region. Autosomal recessive was the most common pattern of
      inheritance and out of the known 60 genes thought to be involved in the
      pathogenesis of non-syndromic Retinitis pigmentosa, 32(53%) were identified in
      South Asia. Although significant progress has been made in this regard, there are
      many more loci that are yet to be identified. Our study found that significant
      gaps in knowledge exist due to lack of reported literature from countries other
      than Pakistan and India and the absence of cost-effective screening programmes in
      place.

PMID- 29171571
TI  - Bacterial contamination of medical uniforms: a cross-sectional study from Suzhou
      city, China.
AB  - Few studies have been conducted which evaluate the prevalence of contamination of
      medical uniforms in China. The present study was designed to explore the
      characteristics of uniform contamination and associated factors. A total of 120
      participants were enrolled in the study and 122 uniforms were sampled. Each
      uniform was sampled at three different sites to determine the colonisation of
      microorganisms. A total of 366 swab samples were cultured; 294 (80.3%) samples
      yielded various microorganisms and 75(61.5%) uniforms were contaminated with
      bacteria. The uniforms of medical students had the highest prevalence of
      contamination. The cuffs of uniforms were the most easily infected with bacteria.
      Participants who wiped their hands at the back of uniforms had higher
      contamination rate in the hanging part of uniforms. Our study demonstrated that
      medical uniforms can harbour microorganisms. Proper handling of medical uniforms
      and adequate education to medical staffs are required to decrease healthcare
      associated infections.

PMID- 29171572
TI  - Susceptibility pattern of methicillin resistant Staphylococcus aureus to
      vancomycin and other alternate agents: report from a private sector hospital
      laboratory.
AB  - With increasing prevalence of methicillin resistant Staphylococcus aureus in
      clinical settings and injudicious use of antibiotics, resistance among MRSA
      against commonly used antibiotics is increasing. To assess the susceptibility
      pattern of MRSA against vancomycin, linezolid, tigecycline, rifampicin,
      fosfomycin fusidic acid, clindamycin, trimethoprim-sulfamethoxazole and
      teicoplanin, minimum inhibitory concentrations (MICs) for given antimicrobials
      were performed on 234 MRSA clinical isolates using automated VITEK 2 system.
      Vancomycin, linezolid, rifampicin, clindamycin, co-trimoxazole and teicoplanin
      susceptibilities were interpreted according to CLSI breakpoints, while
      tigecycline, fosfomycin and fusidic acid were interpreted according to BSAC
      breakpoints. All isolates were found susceptible to vancomycin, tigecycline,
      teicoplanin and linezolid. Non-susceptibility of the isolates for rifampicin,
      fusidic acid and fosfomycin was noted for 58(25%). Co-trimoxazole and clindamycin
      were found less susceptible showing high resistance rates of 61.5% and 42.3%,
      respectively. Vancomycin resistance was not found, however an increased MIC of 1
      mg/ml was observed in about 25% of clinical strains. Increase in vancomycin MICs
      in MRSA is of concern and alternative antimicrobial options must be evaluated and
      considered for treatment of MRSA infections. Continuous antimicrobial
      surveillance is needed to monitor resistance patterns and detect possible
      emergence of vancomycin non-susceptible isolates.

PMID- 29171573
TI  - Learning about facts of life: perspective from medical students on sources and
      preferences about puberty and sex education in Karachi.
AB  - Puberty heralds the onset of adulthood, and is fraught with complex physiological
      and psychological changes and emotions. In this study, we looked at the sources
      of information about puberty and sex education among males and females, age at
      which they learned about them, and the opinions on the role of schools and
      parents in imparting this education among medical students.A cross-sectional
      pilot study, using convenience sampling was conducted among 153 medical students
      of the Hamdard College of Medicine and Dentistry (HCM&D) in Karachi. Regarding
      most common source of information about puberty; 23 (25.3%) males identified
      friends as the most important source of information. While 31 (50.0%) women
      identified their mothers as the most important source.Regarding most common
      source of information about reproductive systems and sex; 17 (27.4%) women
      identified school teachers as the most common source of information, while 26
      (28.6%) men identified books and magazines.

PMID- 29171574
TI  - Methanol poisoning: 27 years experience at a tertiary care hospital.
AB  - Methanol toxicity can result in serious morbidity and mortality without timely
      diagnosis and treatment. Many cases of methanol poisoning outbreaks have been
      noted in our population but no study has been performed to estimate methanol
      exposure and its outcomes and complications. A retrospective study was conducted
      to review all the cases of methanol poisoning admitted from January 1988 to
      December 2015 at the Aga Khan University Hospital. A total of 35 methanol
      poisoning cases were reported. All the patients were male, and the mean age was
      36.2+/-8.6 years. The mean Glasgow Coma Scale score on presentation in the
      emergency was 10.4 +/- 4.4. Blurring of vision was present in 17 (48%) patients
      while 10 (28%) had complete blindness. Mean arterial pH was 6.8+/-0.5 on arrival.
      Ethanol was given to 30(88%) patients and 12(32%) patients received bicarbonate
      for immediate treatment. A total of 15 (42.8%) patients underwent dialysis, out
      of which only 5 (33.3%) patients survived. Overall, 19 (54.3%) patients expired
      secondary to methanol ingestion.

PMID- 29171575
TI  - A case of hypotriploid chromosome in a patient with acute lymphoblastic
      leukaemia.
AB  - TA 58-61, XXXX, hypotriploid chromosome was detected in the cytogenetics report
      of a 28 years old female patient, known case of B-cell Acute Lymphoblastic
      Leukaemia. On admission, the patient had normal physical examination findings and
      mental status, except history of fever spikes and generalized bone pains. The
      patient was admitted for induction of chemotherapy. Bone Marrow/Trephine biopsy
      report showed diffuse infiltration with blast cells with overall cellularity
      around 80-85% and suppressed normal haematopoiesis. Hypotriploid chromosome
      number in patients with B-cell Acute Lymphoblastic Leukaemia is a unique finding
      which, according to WHO classification of ALL, is an important prognostic factor
      itself and these cases have a favourable prognosis. There are only a few medical
      reports published about cases with similar presentations in Pakistan. Therefore,
      this case is very unique and further work should be done for better understanding
      of similar presentations and to find out more about its epidemiology.

PMID- 29171576
TI  - An elusive case of dermatomyositis.
AB  - Dermatomyositis is an inflammatory myopathy of unknown aetiology. Muscle
      involvement may eventuate later in the disease course in some patients, who may
      present with typical skin disease without clinical signs of myopathy and are
      referred to as dermatomyositis sine myositis. A 48 year old female presented with
      intermittent urticaria like rashes, diffuse asymmetrical swelling of proximal
      limbs, pain in small joints of hands and fatiguability. Initial laboratory work
      up for immune markers was negative. Three years later, she developed heliotrope
      rash and periorbital oedema with no evidence of muscle weakness and was labeled
      as amyopathic dermatomyositis. After an interval of one year, she developed
      profound weakness and significantly raised CPK. Patient responded well to
      steroids and Azathioprine and improved both clinically and biochemically.

PMID- 29171577
TI  - A case of Vogt Koyanagi Harada disease in a 16 year old girl.
AB  - Vogt Koyanagi Harada (VKH) is an autoimmune disease with widespread systemic
      manifestations. It typically presents with bilateral sudden painless loss of
      vision. It is mainly characterized by serous retinal detachment, iridocyclitis
      and choroidal swelling. The disease is more common in females and maximus
      incidence occurs in the age group of 30 to 40 years. We present a case of a 16
      year-old girl who presented with sudden bilateral painless loss of vision. Fundus
      examination and OCT scanning confirmed bilateral serous retinal detachment.
      Patient was started on IV methylprednisolone and the patient showed excellent
      response with marked improvement in visual acuity. VKH is very uncommon in
      children and is usually missed. It is important for general practitioners and
      ophthalmologists to know about this rare cause of painless loss of vision so that
      it could be managed adequately.

PMID- 29171578
TI  - Neurobrucellosis: A report of two cases.
AB  - Neurobrucellosis is a rare complication of brucellosis, a common zoonosis with
      multisystem involvement. Its clinical presentation is quite heterogeneous and
      diagnosis requires a high index of suspicion in patients from endemic areas. We
      present two cases of neurobrucellosis with widely varying clinical involvement
      from a tertiary center in Pakistan. Our case report emphasizes that
      neurobrucellosis should be considered in evaluation of patients with unexplained
      neurological symptoms..

PMID- 29171579
TI  - Common clinical features of pediatric multiple sclerosis in Pakistan - A report
      of 15 cases.
AB  - The aim of this note is to assess the common clinical features of paediatric
      multiple sclerosis (PMS) in Pakistan. For this purpose, 150 MS patients with the
      age range of (1-72) years and mean age (34.2+/-11.09) years were studied during
      the period 2010 to 2015 from MRI centers of Pakistan. We found 15 paediatric MS
      cases which had clinical course relapsing-remitting MS (11), secondary
      progressive MS (3) and primary-progressive MS (1). Revised McDonald criteria 2010
      of MRI was used to disseminate lesions in space and time. Sensory symptoms were
      found 27% in PMS patients and contributed brain area of corpus callosum, brain
      stem, periventricle, basal ganglia, white matter and cerebellum. Optic neuritis
      was the second clinical feature and its prevalence was reported 20% in paediatric
      patients. In conclusion, Paediatric multiple sclerosis is predicted 10 % with
      mean age 11.2 years in Pakistan. Sensory and optic neuritis are suggested the
      common clinical features of paediatric multiple sclerosis in Pakistan.

PMID- 29171580
TI  - Effectiveness of locking compression plate in wedge fracture of diaphysis of
      radius and ulna in adults: A descriptive case series.
AB  - The aim of the study was to see the effectiveness of locking compression plate
      (LCP) in wedge fracture of diaphysis of radius and ulna in adults. This
      prospective descriptive case series study inducted total 45 patients presenting
      with wedge fracture (AO Type, 22-B) of radius and/or ulna. The treatment outcome
      of these patients were monitored for 24 weeks in 8 visits. Presence or absence of
      radiological union was noted. The functional outcome was evaluated in terms of
      Disability of Arm, Shoulder and hand (DASH) score and Grace and Eversmann
      criteria. Mean age of the patients included in this study was 28.76+/-6.16 years
      (range 18-47 years). Among them 28 (62.2%) were male while 17 (37.8%) were
      females. Union was achieved in all the patients at mean time of 12.62+/-2.24
      weeks (range 8-16 weeks). Mean DASH score was 12.20+/-4.3 (range 5-19).According
      to Grace and Eversmann criteria, 41 (91.1%) had excellent result, 3 (6.7%) had
      good result, 1 (2.2%) had satisfactory results while there was no patient with
      unsatisfactory result. High rate of union along with good functional outcome and
      minimal complication can be achieved in patients with diaphyseal wedge fracture
      of radius and/ or ulna when managed with locking compression plate.

PMID- 29171581
TI  - Risk stratification of persons on premixed insulin in Ramadan.
AB  - The International Diabetes Federation (IDF), in collaboration with the Diabetes
      and Ramadan (DAR) International Alliance, has recently published practical
      guidelines on the management of diabetes and Ramadan .The risk stratification
      categorizes all persons wishing to fast into three groups, based upon potential
      risk. In spite of evidence to the contrary, all persons using premixed insulin
      are categorized as having high risk. In this article, we present data from
      randomized controlled trials, and discuss the placement of premixed insulin in
      the risk stratification framework.

PMID- 29171582
TI  - The sixth vital sign in diabetes.
AB  - The vital signs are an integral part of clinical methods. In diabetes,
      determination of plasma glucose can be taken as the fifth vital sign. The sixth
      vital sign is well being, which can easily be measured by two item questionnaires
      designed to assess distress, depression and coping skills. This sign is essential
      for the screening and follow up of persons living with diabetes, as it provides
      an idea of quality of care, helps plan therapeutic interventions, and serves as a
      surrogate for prognosis or outcome. Inclusion of the sixth vital sign reflects
      the relevance of the bio-psychosocial model of health to diabetes care.

PMID- 29171583
TI  - Comparison between endoscopic and microscopic approaches for surgery of pituitary
      tumours.
AB  - Surgical techniques for resection of pituitary tumours have come a long way since
      it was first introduced in late 18th century. Nowadays, most pituitary surgeries
      are performed through trans-nasal trans-sphenoidal approach either using a
      microscope, or an endoscope. Herein the authors review the literature and compare
      these two instruments with regards to their outcomes when used for resection of
      pituitary tumours. .

PMID- 29171584
TI  - A case for setting-up dedicated peritoneal surface malignancy centers in
      Pakistan.

PMID- 29171585
TI  - Content validation of the Urdu version of international prostate symptom score.

PMID- 29171586
TI  - Concordance of cerebrospinal fluid latex particle agglutination test with CSF and
      blood culture among children with acute bacterial meningitis.

PMID- 29171587
TI  - Comment on Mohammad Hamid et al (J Pak Med Assoc. 67: 1019; 2017).

PMID- 29171588
TI  - Response to comment on Mohammad Hamid et al (J Pak Med Assoc. 67: 1019; 2017) -
      Incidence and pattern of Thrombocytopenia in cardiac surgery patients.

PMID- 29171589
TI  - Comment on Sanjay Kalra et al (J Pak Med Assoc. 2017; 5: 810-813) - Diabetes
      mellitus, malaria and HbA1c levels.

PMID- 29171590
TI  - Response to comment on Sanjay Kalra et al (J Pak Med Assoc. 2017; 5: 810-813) -
      Malaria, red blood cells turnover and glycated hemoglobin: Pitfalls and
      challenges.

PMID- 29171591
TI  - Knowledge about asthma: A cross-sectional survey in 4 major hospitals of Karachi,
      Pakistan.
AB  - OBJECTIVE: To determine knowledge and misconceptions about asthma among the local
      population.. METHODS: This cross-sectional study was conducted at four tertiary
      care hospitals; Aga Khan University Hospital, Civil Hospital Karachi, Jinnah
      Postgraduate Medical Centre and Ojha Institute of Chest Diseases, Karachi, from
      October to November 2016, and comprised hospital attendants. The questionnaire
      used in the study comprised 26 questions answered with a true, false or not sure
      answer.SPSS 20 was used for data analysis. RESULTS: There were 400 participants.
      The overall mean age was 41.2+/-14.2 years, and 214(53.5%) of the participants
      were males. Moreover, 75(19%) participants thought that asthma was a
      psychological disorder while 181(45%) considered it an infectious disease. Nearly
      174(43.5%) believed that inhaled medications had significant side effects.
      Besides, 264(66%) participants considered steam inhalation to be an effective
      treatment for asthma, 269(67%) thought that patients with asthma should avoid
      rice in their diet and 167(42%) considered milk as a common trigger. CONCLUSIONS:
      Participants' knowledge about asthma was poor and misconceptions were common
      about the condition.

PMID- 29171592
TI  - Frequency of different lifestyle modification measures among patients with GERD
      based on monthly income.
AB  - A cross-sectional study was carried out at Shifa International Hospital Islamabad
      over a period of 6 months, to determine the frequency and compare the different
      lifestyle modifications among patients with Gastroesophageal Reflux Disease
      (GERD) of different monthly income groups. Two hundred patients of GERD were
      enrolled in the study and divided into two groups based on monthly income less
      than and more than Rs. 30,000 respectively. Data was analyzed using SPSS 21.
      Descriptive statistics were calculated. Chi-square test was applied keeping p
      value <0.05. Mean age was 40+/-13 years, 82 (41%) males and 118 (59%) females.
      Walking was undertaken by 32% after meals and 87.5% consumed tea. Significant
      difference was seen between income groups and higher intake of fried and spicy
      foods respectively. Thus, effort needs to be made in creating awareness and
      counseling patients to practice lifestyle modifications to reduce GERD symptoms
      and stop sole reliance on medications.

PMID- 29171593
TI  - Corrigendum: Synchronicity and Rhythmicity of Purkinje Cell Firing during
      Generalized Spike-and-Wave Discharges in a Natural Mouse Model of Absence
      Epilepsy.
AB  - [This corrects the article DOI: 10.3389/fncel.2017.00346.].

PMID- 29171594
TI  - On-chip conductometric detection of short DNA sequences via electro-hydrodynamic
      aggregation.
AB  - Fluorescence measurement is the main technology for post-amplification DNA
      detection in automated systems. Direct electrical reading of DNA concentration in
      solution could be an interesting alternative to go toward more miniaturized or
      less expensive devices, in particular in the pathogen detection field. Here we
      present the detection of short bacterial biomarkers with a direct impedancemetric
      measurement, within solutions of amplified and elongated DNA sequences in a
      microchannel. This technology relies on the electrohydrodynamic instability
      occurring in solutions of long charged macromolecules in a strong electric field.
      This instability specifically induces the aggregation of long DNAs and triggers
      conductivity variations that can be monitored by on-contact conductometry. An
      innovative isothermal amplification and elongation strategy was developed,
      combining SDA and HRCA reactions, in order to yield long DNAs suitable to be
      detected by the above principle, from a dilute initial DNA target. In contrast
      with previous label-free detection methods, this new strategy is very robust to
      matrix effects, thanks to the unique molecular weight dependence of the
      instability, coupled with this specific DNA amplification strategy. We
      demonstrate the detection of a 1 pM gene sequence specific to Staphylococcus
      aureus, in a portable system.

PMID- 29171595
TI  - An "on-off" switchable cubic phase with exceptional thermal stability and water
      sorption capacity.
AB  - We report on the phase behaviour of a wedge-shaped mesogen, which can exist in
      two different states at room temperature, a stable columnar and a metastable
      cubic gyroid phase. The latter reveals exceptional stability and remarkable water
      sorption capacity accounted for by the locally-ordered peripheral alkyl chains.

PMID- 29171596
TI  - A ratiometric fluorogenic probe for the real-time detection of SO32- in aqueous
      medium: application in a cellulose paper based device and potential to sense SO32
      in mitochondria.
AB  - A new water soluble and fluorogenic probe (L) that can demonstrate a specific
      ratiometric detection of a SO2 derivative (SO32-) in 100% aqueous medium and live
      cells has been designed and synthesized. The detection process can be visualized
      by the naked eye, as the orange-red fluorescence of L turns into a strong blue
      fluorescence upon interaction with SO32-. L displayed several beneficial
      attributes such as detection in complete aqueous medium, extremely fast response
      time along with high selectivity and sensitivity. The ratiometric sensing was
      attributed to the selective nucleophilic addition reaction of SO32- with L. The
      probe was further used to develop a low cost microfluidic sensor device (MUPAD).
      The probe was biocompatible and its potential to sense SO32- in mitochondria was
      captured in live HeLa cells.

PMID- 29171597
TI  - Self-sorted pore-formation in the construction of heteropore covalent organic
      frameworks based on orthogonal reactions.
AB  - Two heteropore COFs have been constructed by taking advantage of orthogonal
      dynamic covalent bonds. And an unprecedented self-sorted pore-formation in the
      polymerization process was observed, from which micropores with distinctive
      bonding manners were produced.

PMID- 29171598
TI  - Continuous wave random lasing in naturally occurring biocompatible pigments and
      reduction of lasing threshold using triangular silver nanostructures as
      scattering media.
AB  - Random lasers have enormous applications in several fields including speckle-free
      imaging and bio-imaging. Thus, recently, random laser (RL) generation (mostly
      under pulsed operation) has been demonstrated in several commercial organic dyes
      with high photoluminescence quantum yields (PLQY). Although some commercial
      organic dyes have high PLQYs, these have several limitations; particularly, these
      dyes are not bio-compatible and thus cannot be used in in vivo bio-imaging. In
      this study, rarely reported bio-inspired continuous-wave (CW) RL generation has
      been demonstrated at ca. 674 nm, pumped by a low power He-Ne laser, in naturally
      occurring pigments of Hibiscus rosa-sinensis leaves extract (HRLe). The lasing
      threshold was reduced by ~2.4 times from 40.7 W cm-2 (without scatterer) to 16.8
      W cm-2 using anisotropic triangular nanostructures of silver (TNS) as a scatterer
      with a typical number density of 8 * 1015 nos. per ml. Unprecedentedly, further
      RL generation at ca. 691.7 nm with spectrally narrowed emission modes with a line
      width of ca. 1 nm along with a very low lasing threshold of 15 W cm-2 has been
      demonstrated in a thin film of polyvinyl alcohol doped with methylene blue dye
      and TNS. This study will initiate a new era of development of bio-inspired RL for
      bio-photonics applications.

PMID- 29171599
TI  - Ginger fermented with Schizosaccharomyces pombe alleviates memory impairment via
      protecting hippocampal neuronal cells in amyloid beta1-42 plaque injected mice.
AB  - Ginger, which has been widely used for dietary condiment, has been reported to
      improve memory dysfunction in an animal model of Alzheimer's disease (AD).
      Recently, a few trials have been carried out to enhance the effects of ginger by
      improving the bioavailability of its relevant components via fermentation. Some
      reports have suggested that the fermented ginger has the ability to affect the AD
      in vitro systems; however, its anti-amnesic effects on an in vivo model still
      remain to be investigated. In the present study, we aimed to investigate the
      neuroprotective effects of ginger fermented with Schizosaccharomyces pombe (FG)
      in the in vivo models of AD. The neuroprotective effects were investigated by
      employing behavioral, western blotting, and immunohistochemical assays. The
      administration of FG improved recognition memory, impaired by scopolamine
      injection, than that of non-fermented ginger. In addition, FG ameliorated memory
      impairment in amyloid beta1-42 (Abeta1-42) plaque-injected mice via protecting
      neuronal cells in the CA3 area of the mouse hippocampus. Moreover, FG reinstated
      the pre- and postsynaptic protein levels decreased by Abeta1-42 plaque-toxicity.
      Overall, these data suggest that FG attenuates memory impairment in Abeta1-42
      plaque-induced AD mice through inhibition of neuronal cell loss and synaptic
      disruption.

PMID- 29171600
TI  - Photo-degradation of high efficiency fullerene-free polymer solar cells.
AB  - Polymer solar cells are a promising technology for the commercialization of low
      cost, large scale organic solar cells. With the evolution of high efficiency
      (>13%) non-fullerene polymer solar cells, the stability of the cells has become a
      crucial parameter to be considered. Among the several degradation mechanisms of
      polymer solar cells, burn-in photo-degradation is relatively less studied.
      Herein, we present the first systematic study of photo-degradation of novel PBDB
      T:ITIC fullerene-free polymer solar cells. The thermally treated and as-prepared
      PBDB-T:ITIC solar cells were exposed to continuous 1 sun illumination for 5
      hours. The aged devices exhibited rapid losses in the short-circuit current
      density and fill factor. The severe short-circuit current and fill factor burn in
      losses were attributed to trap mediated charge recombination, as evidenced by an
      increase in Urbach energy for aged devices.

PMID- 29171601
TI  - Debye ring diffraction elucidation of 2D photonic crystal self-assembly and
      ordering at the air-water interface.
AB  - We fabricate 2D photonic crystals (2DPC) by spreading a dispersion of charged
      colloidal particles (diameters = 409, 570, and 915 nm) onto the surface of
      electrolyte solutions using a needle tip flow method. When the interparticle
      electrostatic interaction potential is large, particles self-assemble into highly
      ordered hexagonal close packed (hcp) monolayers. Ordered 2DPC efficiently forward
      diffract monochromatic light to produce a Debye ring on a screen parallel to the
      2DPC. The diameter of the Debye ring is inversely proportional to the 2DPC
      particle spacing, while the Debye ring brightness and thickness depends on the
      2DPC ordering. The Debye ring thickness increases as the 2DPC order decreases.
      The Debye ring ordering measurements of 2DPC attached to glass slides track
      measurements of the 2D pair correlation function order parameter calculated from
      SEM micrographs. The Debye ring method was used to investigate the 2DPC particle
      spacing, and ordering at the air-solution interface of NaCl solutions, and for
      2DPC arrays attached to glass slides. Surprisingly, the 2DPC ordering does not
      monotonically decrease as the salt concentration increases. This is because of
      chloride ion adsorption onto the anionic particle surfaces. This adsorption
      increases the particle surface charge and compensates for the decreased Debye
      length of the electric double layer when the NaCl concentration is below a
      critical value.

PMID- 29171602
TI  - The benchmark of 31P NMR parameters in phosphate: a case study on structurally
      constrained and flexible phosphate.
AB  - A benchmark for structural interpretation of the 31P NMR shift and the 2JP,C NMR
      spin-spin coupling in the phosphate group was obtained by means of theoretical
      calculations and NMR measurements in diethylphosphate (DEP) and 5,5-dimethyl-2
      hydroxy-1,3,2-dioxaphosphinane 2-oxide (cDEP). The NMR parameters were calculated
      employing the B3LYP, BP86, BPW91, M06-2X, PBE0, KT2, KT3, MP2, and HF methods,
      and the 6-31+G(d), Iglo-n (n = II, III), cc-pVnZ (n = D, T, Q, 5), aug-cc-pVnZ (n
      = D, T and Q), and pcS-n and pcJ-n (n = 1, 2, 3, 4) bases, including the solvent
      effects described with explicit water molecules and/or the implicit Polarizable
      Continuum Model (PCM). The effect of molecular dynamics (MD) on NMR parameters
      was MD-calculated using the GAFF force field inclusive of explicit hydration with
      TIP3P water molecules. Both the optimal geometries and the dynamic behaviors of
      the DEP and cDEP phosphates differed notably, which allowed a reliable
      theoretical benchmark of the 31P NMR parameters for highly flexible and
      structurally constrained phosphate in a one-to-one relationship with the
      corresponding experiment. The calculated 31P NMR shifts were referenced employing
      three different NMR reference schemes to highlight the effect of the 31P NMR
      reference on the accuracy of the calculated 31P NMR shift. The relative
      Deltadelta(31P) NMR shift calculated employing the MD/B3LYP/Iglo-III/PCM method
      differed from the experiment by 0.16 ppm while the NMR shifts referenced to H3PO4
      and/or PH3 deviated from the experiment notably more, which illustrated the
      superior applicability of the relative NMR reference scheme. The 2JP,C coupling
      in DEP and cDEP calculated employing the MD/B3LYP/Iglo-III(DSO,PSO,SD)/cc
      PV5Z(FC)/PCM method inclusive of correction due to explicit hydration differed
      from the experiment by 0.32 Hz and 0.15 Hz, respectively. The NMR calculations
      demonstrated that reliable structural interpretation of the 31P NMR parameters in
      phosphate must involve both the structural and the dynamical components.

PMID- 29171603
TI  - The remarkable influence of N,O-ligands in the assembly of a bis-calix[4]arene
      supported [MnMnMn] cluster.
AB  - Calix[4]arenes are versatile ligands, capable of supporting the formation of a
      wide variety of polymetallic clusters comprising 3d, 4f or 3d-4f metal ions.
      Calixarene-based metal ion fragments act as both bridging and structure capping
      moieties in these systems, and this behaviour is systematically extended upon
      moving to bis-calix[4]arene, a relatively new ligand in which two calix[4]arenes
      are tethered at the methylene bridge position. N,O-Ligands greatly influence
      cluster formation with bis-calix[4]arene, affording a remarkable mixed-valence
      [MnMnMn] cluster that displays coordination chemistry typical of each ligand
      type, but also new structure capping behaviour for the latter.

PMID- 29171604
TI  - Sensitivity-enhanced detection of non-labile proton and carbon NMR spectra on
      water resonances.
AB  - Chemical exchange saturation transfer (CEST) experiments enhance the NMR signals
      of labile protons by continuously transferring these protons' saturation to an
      abundant solvent pool like water. The present study expands these principles by
      fusing into these experiments homonuclear isotropic mixing sequences, enabling
      the water-enhanced detection of non-exchangeable species. Further opportunities
      are opened by the addition of coupling-mediated heteronuclear polarization
      transfers, which then impose on the water resonance a saturation stemming from
      non-labile heteronuclear species like 13C. To multiplex the ensuing experiments,
      these relayed approaches are combined with time-domain schemes involving multiple
      Ramsey-labeling experiments imparting the frequencies of the non-labile sites on
      the water resonance, via chemical exchange. 13C and 1H NMR spectra were detected
      in this fashion with about two-fold SNR amplification vis-a-vis conventionally
      detected spectroscopies. When combined with non-uniform sampling principles, this
      methodology thus becomes a sensitive alternative to detect non-exchangeable
      species in biomolecules. Still, multiple parameters including the scalar
      couplings and solvent exchange rates, will affect the efficiency and consequently
      the practicality of the overall experiment.

PMID- 29171605
TI  - A Europium ion post-functionalized indium metal-organic framework hybrid system
      for fluorescence detection of aromatics.
AB  - A Eu3+-functionalized In-MOF (In(OH)bpydc, bpydc = 2,2'-bipyridine-5,5'
      dicarboxylate) hybrid system (In-MOF-Eu) with dual-emission is investigated for
      fluorescence sensing of benzene homologues (BTEX) in both vapor and liquid
      phases. A fluorescence test paper and a 2D-decoded map were designed to provide
      the potential for the convenient distinction of BTEX.

PMID- 29171606
TI  - Dynamics of poly(vinyl butyral) studied using dielectric spectroscopy and 1H NMR
      relaxometry.
AB  - Dielectric Spectroscopy (DS) and 1H Fast Field-Cycling (FFC) NMR relaxometry were
      applied for understanding the dynamic behavior of the amorphous ter-polymer
      poly(vinyl butyral) (PVB) across the glass transition temperature (Tg = 70 
      degrees C by Differential Scanning Calorimetry). Above Tg, main chain segmental
      motions (alpha relaxation) were detected and characterized using both DS and FFC
      NMR relaxometry. The correlation times extracted by the analysis of DS and FFC
      NMR relaxometry data agreed within a factor of three and showed a Vogel-Fulcher
      Tammann temperature dependence, with an associated Tg of 69  degrees C and a
      fragility of 155 for PVB glass. Below Tg, a secondary process (beta relaxation)
      was revealed by DS, and was ascribed to reorientations of the vinyl alcohol
      dipoles due to local twisting motions with an associated activation barrier of 11
      kcal mol-1. The beta process was also found to contribute to 1H NMR relaxation
      above Tg.

PMID- 29171607
TI  - Towards single egg toxicity screening using microcoil NMR.
AB  - Planar microcoils with diameter ranging from 20 to 1000 MUm I.D. (130-1130 MUm
      O.D.) are evaluated for their applications in NMR spectroscopy. The coils are
      first overfilled with a standard sucrose solution and compared against each
      other. Coils with smaller I.D. (<=100 MUm) perform extremely well. One hypothesis
      is that as the coils get smaller the volume occupied by the copper turns
      increases relative to the open I.D.; as such a large proportion of the sample is
      brought in close proximity to the coil turns and likely gives rise to strong
      sample-coil magnetic coupling, which increases the signal. The applications of
      the planar microcoils are demonstrated on Cypselurus poecilopterus (fish) and
      Daphnia magna (water flea) eggs. A single D. magna egg on a 50 MUm coil yielded
      at least 3000 times the mass sensitivity (~9,000,000 time saving) when compared
      to a 5 mm probe. This value could be at least 4 times higher if the B1
      homogeneity of the coils could be improved. With the current design, 80% of the
      signal is lost in multiple pulse experiments that rely on phase inversion and
      signal cancellation between scans. The data were extrapolated to predict that
      biological samples as small as ~4 MUm may become accessible via planar microcoil
      designs. To fulfill their potential for in situ metabolic screening, specialized
      magnetic susceptibility matched sample holders that restrict the sample to the
      homogeneous B1 field region (i.e. within the 90% RF field) of the coil and
      advanced experiments that narrow spectral lines, suppress lipids and disperse
      signals into multiple dimensions will be required.

PMID- 29171608
TI  - Template-free synthesis and structural evolution of discrete hydroxycancrinite
      zeolite nanorods from high-concentration hydrogels.
AB  - We report the synthesis and characterization of hydroxycancrinite zeolite
      nanorods by a simple hydrothermal treatment of aluminosilicate hydrogels at high
      concentrations of precursors without the use of structure-directing agents.
      Transmission electron microscopy (TEM) analysis reveals that cancrinite nanorods,
      with lengths of 200-800 nm and diameters of 30-50 nm, exhibit a hexagonal
      morphology and are elongated along the crystallographic c direction. The powder X
      ray diffraction (PXRD), Fourier transform infrared (FT-IR) and TEM studies
      revealed sequential events of hydrogel formation, the formation of aggregated
      sodalite nuclei, the conversion of sodalite to cancrinite and finally the growth
      of cancrinite nanorods into discrete particles. The aqueous dispersion of the
      discrete nanorods displays a good stability between pH 6-12 with the zeta
      potential no greater than -30 mV. The synthesis is unique in that the initial
      aggregated nanocrystals do not grow into microsized particles (aggregative
      growth) but into discrete nanorods. Our findings demonstrate an unconventional
      possibility that discrete zeolite nanocrystals could be produced from a
      concentrated hydrogel.

PMID- 29171609
TI  - A pillar[5]arene based gel from a low-molecular-weight gelator for sustained dye
      release in water.
AB  - A soft gel based on pillar[5]arene was successfully prepared using a carbazone
      reaction. Furthermore, dyes such as TPP or TPPE can be incorporated into this gel
      and were observed to be released in a sustained way in water due to solvent
      exchange.

PMID- 29171610
TI  - Biological application of water-based electrochemically synthesized CuO leaf-like
      arrays: SERS response modulated by the positional isomerism and interface type.
AB  - Cupric oxide leaf-like nanostructures (CuONSs) (average dimensions: 80-180 nm in
      width and 400-750 nm in length) were synthesized via anodic electrochemical
      dissolution of copper in an ethanol solution containing LiCl electrolyte and
      water. Ultraviolet-visible (UV-Vis), Fourier-transform infrared (FT-IR), and
      Raman spectroscopies as well as scanning electron microscope (SEM), high
      resolution transmission electron microscopy with energy dispersive X-ray (HD-TEM
      EDS), X-ray photoelectron spectroscopy (XPS), and X-ray powder diffraction (XRD)
      were used to explore the metal surface plasmon, size, rheology, and structure of
      CuONSs. Then, pyridine alpha-aminophosphinic acid isomers (alpha-, beta-, and
      gamma-NHPy) were synthesized and assembled on the CuONS/air and CuONS/aqueous
      solution interfaces at the pH level of solution = 7. Differences in adsorption
      and thus in the spectral response resulting from positional isomerism were
      examined by surface-enhanced Raman scattering (SERS) with an excitation
      wavelength of 785 nm. The manner of interaction of the investigated isomers with
      CuONSs in an aqueous solution was discussed in detail and compared with that at
      the CuONS/air interface. For gamma-NHPy, at the CuONS/water interface, the time
      dependent changes in the spectral profile were observed and analyzed. For beta
      NHPy at the CuONS/air interface, tip-enhanced Raman scattering (TERS)
      measurements were performed. These measurements allowed observing single molecule
      behavior and avoiding interference from the molecule's surrounding environment.

PMID- 29171611
TI  - Loosely packed monolayer coffee stains in dried drops of soft colloids.
AB  - We report a complete suppression of the coffee-ring effect resulting in the
      formation of loosely packed two-dimensional particle monolayers by controlled
      evaporation of sessile drops containing soft microgel particles. These
      particulate deposits show gradual order-to-disorder transitions that are not
      abrupt like deposits of hard colloids. The areal coverage of the monolayer
      deposits can also be precisely controlled by tuning the particle concentration.
      The preferential adsorption of soft-microgel particles to the water-vapor
      interface, and their radial flow along the interface towards the drop edge
      facilitates the creation of the novel monolayer deposits.

PMID- 29171612
TI  - Design of superhalogens using a core-shell structure model.
AB  - Superhalogens, which have larger electron affinity than any halogen, play an
      important role in physical chemistry and materials design because of their
      applications in hydrogen storage and lithium-ion batteries. Inspired by the
      unique geometries and electronic properties of II-VI/III-V cage clusters,
      particularly the experimentally synthesized B12N12, we propose a core-shell
      structure model to design new superhalogens. The idea is assessed by conducting
      ab initio calculations on endohedral cage clusters X@B12N12 (X = F, Cl, Br) and
      other similar systems. With an exceptionally large electron affinity of 5.36 eV,
      the stable F@B12N12 cluster behaves as a novel superhalogen that can serve as a
      building block for Li salts and hyperhalogens. The findings highlight a new route
      for the discovery of superhalogens and provide useful building blocks for the
      bottom-up design of materials.

PMID- 29171613
TI  - Photo-induced radical polarization and liquid-state dynamic nuclear polarization
      using fullerene nitroxide derivatives.
AB  - We report on radical polarization and optically-driven liquid DNP using nitroxide
      radicals functionalized by photoexcitable fullerene derivatives. Pulse laser
      excitation of the fullerene moiety leads to transient nitroxide radical
      polarization that is one order of magnitude larger than that at the Boltzmann
      equilibrium. The life time of the radical polarization increases with the size of
      the fullerene derivative and is correlated with the electronic spin-lattice
      relaxation time T1e. Overhauser NMR signal enhancements of toluene solvent
      protons were observed under steady-state illumination, which replaced microwave
      irradiation.

PMID- 29171614
TI  - The Yin and Yang of coordinating co-solvents in the size-tuning of Fe3O4
      nanocrystals through flow synthesis.
AB  - The present study reports a continuous flow synthesis of differently sized Fe3O4
      nanocrystals stabilized by oleylamine and oleic acid. Oleylamine and oleic acid
      are particularly investigated to elucidate their roles in tailoring the size and
      magnetic properties of the resulting particles potentially useful for magnetic
      resonance imaging.

PMID- 29171615
TI  - Data Sharing Statements for Clinical Trials: A Requirement of the International
      Committee of Medical Journal Editors.
AB  - El Comite Internacional de Editores de Revista Medicas (ICMJE) ha tomado la
      posicion que el compartir los datos generados por los ensayos clinicos es una
      obligacion etica, por cuanto los participantes en esos estudios se colocaron en
      riesgo al aceptar su inclusion. En esta editorial el ICMJE expresa que requerira
      desde Julio 2018 que los manuscritos enviados a sus revistas deben incluir una
      declaracion sobre compartir datos. A su vez, los ensayos clinicos que comiencen a
      enrolar pacientes a partir de Enero 2019, deben incluir un plan sobre compartir
      datos en el registro de tales ensayos. Se dan en esta declaracion cuatro ejemplos
      de declaraciones sobre compartir datos, referidos a que datos se compartiran,
      cuando estaran disponibles y que criterios de acceso se estableceran. El ICMJE
      visualiza un futuro cercano en el cual el compartir los datos sera la norma, con
      el fin de maximizar el conocimiento ganado por los esfuerzos y sacrificios de los
      participantes.

PMID- 29171616
TI  - [Adverse event prediction in immunocompetent adult patients hospitalized with
      community-acquired pneumonia].

PMID- 29171617
TI  - [Incidence and hospital mortality due to heart failure. Are there any differences
      by sex?]

PMID- 29171618
TI  - [Experience with anticoagulation with bivalirudin during extracorporeal membrane
      oxygenation].

PMID- 29171619
TI  - [Risk factors for obesity: analysis of the 2009-2010 Chilean health survey].

PMID- 29171620
TI  - [Inequality of financial resources for primary health care].

PMID- 29171621
TI  - [Galectin-3 levels in patients hospitalized for decompensated heart failure].

PMID- 29171622
TI  - [Association between antral follicle count and age in fertile women].

PMID- 29171623
TI  - [A scale to assess spiritual symptoms in palliative care].

PMID- 29171624
TI  - [Antimicrobial susceptibility of bacteria causing urosepsis].

PMID- 29171625
TI  - [The risks of avoiding hormone replacement therapy during menopause].

PMID- 29171626
TI  - [Exercise as a tool to reduce body weight].

PMID- 29171627
TI  - [Biological and genetic mechanisms underlying the placebo effect].

PMID- 29171628
TI  - [International cooperation. Where are we, and where are we heading to?]

PMID- 29171629
TI  - [The ethical challenge of "healthy patients"].

PMID- 29171630
TI  - [Elbow monoarthritis and bone infarction as a form of presentation of B cell
      lymphoma. Case report].

PMID- 29171631
TI  - [Liver transplant as treatment for cardiac failure secondary to hereditary
      hemorrhagic telangiectasia. Report of one case].

PMID- 29171632
TI  - [Acute lymphoblastic leukemia causing hepatic failure. Report of two cases].

PMID- 29171633
TI  - [Stridor and dyspnea caused by a conversion disorder. A case report].

PMID- 29171634
TI  - [Extramedullary mediastinal plasmacytoma. Report of one case].

PMID- 29171635
TI  - [Epydemiologic role of Olygoryzomys longicaudatus (long tail rodent) in three
      zoonotics diseases in Chile].

PMID- 29171636
TI  - [Expanding opportunities to promote functionality and prevent dependency in older
      adults].

PMID- 29171637
TI  - [Publication in students' scientific journals. Is it the answer to undergaduates
      on where to publish their work?]

PMID- 29171638
TI  - Can beliefs about musculoskeletal pain and work be changed at the national level?
      Prospective evaluation of the Danish national Job & Body campaign.
AB  - Objectives This study evaluates the Danish national Job & Body campaign on
      beliefs about musculoskeletal pain and work. Methods Initiated in 2011, a
      national campaign in Denmark targeted public sector employees with a mixture of
      networking activities, workplace visits, and a mass media outreach with topics
      related to job and body (eg, musculoskeletal pain, movement and work) and
      creating balance between demands at work and physical capacity. At baseline
      (2011) and at four time points until the end of 2014, random cross-sectional
      samples of >=>=1000 representative public sector employees (total N=5012) replied
      to eight questions concerning beliefs about musculoskeletal pain and work.
      Changes over time were modelled using general linear models (averaged for all
      questions, 0-100 points, where 0 is completely negative and 100 completely
      positive) and logistic regression analyses (for the single questions) controlling
      for age, gender and a number of work-related factors. Results At the last follow
      up in 2014, 17.3% of public sector employees were familiar with the campaign.
      Beliefs about musculoskeletal pain and work were 3.4 points (95% CI 2.4-4.3)
      higher than at baseline. For the single questions, 4 out of 8 showed improved
      odds for more positive beliefs [odds ratios (OR) of 1.28-1.89]. Conclusion During
      follow-up of the national campaign, beliefs about musculoskeletal pain and work
      were more positive among public sector employees in Denmark. Due to the time-wise
      mixture of several campaign activities, the isolated effect of each component
      could not be disentangled. Whether changes in health occurred remain unknown.

PMID- 29171639
TI  - Nutritional supplements in depressive disorders.
AB  - There is increasing evidence about the role of nutrients in mental health. An
      adequate intake of nutrients contributes to better overall health and mental
      health in particular. Major depression is a severe mental illness with a high
      prevalence for which effective treatments exist but not in all cases the
      patient&#8217;s remission is achieved. Therefore, it is increasingly aimed at
      optimizing the supply of nutrients necessary for adequate brain functioning as
      adjunctive therapy to antidepressant treatment in depressive disorders. In this
      article we review those nutrients that have been related to depression: Omega-3
      fatty acids, B vitamins, s-adenosylmethionine, tryptophan, magnesium, zinc and
      probiotics.

PMID- 29171640
TI  - Nutritional supplements in Anxiety Disorder.
AB  - In recent years, a direct relation between the occurrence of anxiety disorders,
      sleep disturbances, and mood disorders has been observed as a consequence of poor
      or inadequate diet. Eating habits in Western societies have greatly changed in
      recent decades, with an increase in the consumption of foods low in vitamin and
      mineral content, high in caloric value, and rapidly prepared and easily consumed.
      It may be that the new lifestyles that directly affect family organization and
      planning interfere with following a proper diet. However, with increasing
      frequency, especially among young adults, there is interest in healthy and
      balanced nutrition, as well as learning culinary techniques. We reviewed the
      literature for this study, and describe the concept of anxiety and its existence
      in relation to dietary disorders, as well as alternatives for the treatment of
      these symptoms. The characteristics of these disorders and their impact on
      patients are analyzed. The information used in this work was obtained mainly from
      PubMed, PsycARTICLES, PsycCRITIQUES, and PsycINFO. It was retrieved using the
      keywords &#8220;mental health&#8221;, &#8220;nutrition&#8221;,
      &#8220;diet&#8221;, &#8220;phytotherapy&#8221;, &#8220;natural
      alternatives&#8221;, &#8220;anxiety&#8221;, &#8220;mood&#8221;, and &#8220;sleep
      disturbance&#8221;.

PMID- 29171641
TI  - Dietary supplements in child and adolescent psychiatry.
AB  - Complementary and alternative treatments, including dietary supplements, are very
      popular and increasingly used in developed countries. Some features such as
      accessibility, ease of use, the possibility of self-administration and the belief
      they are safe without side effects, have led to an increase in their consumption.
      However, there is limited evidence of the effectiveness and safety of these
      treatments because of methodological issues. The level of scientific evidence is
      particularly low and weak in the field of child and adolescent Psychiatry. The
      purpose of this article is to give an updated overview of dietary treatments in
      this area. We make a brief introduction about general questions, including legal
      aspects, and propose general practical recommendations for a proper management by
      the families that choose these treatments. We focus on reviewing the current
      state of research into dietary treatments in some childhood and juvenile
      psychiatric disorders, highlighting current evidence of specific treatments. The
      final purpose of this article is to describe the level of current evidence on
      dietary treatments and to provide professionals involved in the care of children
      and adolescents with a useful tool to help, guide and educate families about
      their use in order to achieve the greatest benefit to patients.

PMID- 29171642
TI  - Dietary supplements for cognitive impairment.
AB  - Alzheimer disease and the other neurodegenerative dementias as yet have no
      curative treatment. For this reason, the prevention of these conditions and non
      pharmacological treatments are important fields of research at present. The
      Mediterranean diet (rich in fruits, vegetables, legumes, and olive oil, with
      regular fish consumption and low consumption of dairy products and meats) has
      been shown to reduce the incidence of mild cognitive impairment (MCI) and,
      probably, the conversion of MCI to dementia. Vitamins, especially vitamin E and
      the vitamins of the B group, have also been associated with the prevention of
      cognitive impairment due to their antioxidant effects. Ginkgo biloba is one of
      the most widely used supplements in the world for cognitive improvement because
      of its possible effects as a vasodilator and facilitator of cerebral
      vascularization. Green tea polyphenols have shown beneficial effects in different
      diseases, including cognitive impairment. Cerebral aging is associated with
      changes in the lipid composition of neuronal membranes, so it has been suggested
      that treatment with phospholipids like phosphatidylcholine and phosphatidylserine
      could favor cognitive improvement. Similarly, polyunsaturated and omega-3 fatty
      acids, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) supplements
      are associated with a beneficial effect on cognitive function due to the
      cumulative summation of factors that ultimately favor membrane permeability and
      neuronal functioning.

PMID- 29171643
TI  - Nutritional supplements in psychotic disorders.
AB  - There is growing interest about the potential of diet and nutrients to improve
      the mental health of the population and for the treatment of psychiatric
      disorders. In the case of schizophrenia, the limitations of antipsychotic drugs
      to achieve adequate rates of clinical remission and functional recovery have
      promoted the search for complementary approaches. This narrative review
      approaches the dietary patterns and interventions in schizophrenia, efficacy of
      specific nutrients and therapeutic modulation of the gut microflora by
      probiotics. As a whole, schizophrenia patients follow a low-quality diet and are
      exposed to deficiencies in various nutrients that are essential for brain
      functioning. Although clinical trials with nutritional supplements are still
      limited and have inconsistent results, specific nutrients, as Omega-3, vitamin D
      and Group B vitamins can be useful as complementary strategies in the treatment
      of schizophrenia. It is hoped that the initiation of personalized medicine
      strategies, such as stratification and using a clinical staging approach, will
      make it possible to identify the subgroups of patients who can obtain maximum
      benefit from dietary and nutritional interventions.

PMID- 29171644
TI  - Nutritional supplements in eating disorders.
AB  - Eating disorders (EDs) are a series of differentiated nosological entities
      sharing the common link of a continuous alteration in food intake or in food
      intake-related behavior. Within this classification, the following disorders are
      noteworthy: anorexia nerviosa (AN) and bulimia nerviosa (BN). Anorexia nervosa is
      a chronic disorder characterized mainly by negative or decreased food intake
      accompanied by a distortion of body image and intense accompanying fear of weight
      gain. The estimated vital prevalence of this disorder in adolescence is
      approximately 0.5%-1%.1 The primary feature of BN is the presence of binge eating
      accompanied by compensatory behavior (in the form of intense exercise and the use
      of laxatives and diuretics, etc.). The prevalence of BN is estimated to be
      between 2% and 4% in young women, and it generally starts at somewhat later
      stages than AN. It is believed that biological, psychological, and environmental
      factors, as well as genetic vulnerability, influence the pathogenesis of EDs. A
      variety of therapies exist, both biological and psychological, whose
      effectiveness is supported by the scientific literature. Nonetheless, we find
      these therapies only partially effective and new targets as well as new
      treatments should be sought. Although the etiopathogenesis of EDs is unclear,
      some of the neurobiological dysfunction found suggests that diet and nutrient
      supplementation could be relevant in their treatment. We review in this article
      new treatments focusing on nutritional deficits.

PMID- 29171645
TI  - Cardiovascular risk factors and white matter hyperintensities in patients with
      migraine without aura.
AB  - OBJECTIVES: White matter hyperintensities (WMHs) are observed in patients with
      migraine with aura (MWA) and without aura (MWO), but there are a limited number
      of studies regarding patients with MWA. In this study, we aimed to investigate
      the cardiovascular risk factors which may play a role in the development of WMHs
      in patients with MWO. METHODS: This observational, analytical, case-control study
      was conducted between June 2016 and January 2017. It included 21 patients with
      MWO who had WMHs on brain MRI and 19 patients with MWO who tested normal on MRI
      (control group) at the Neurology Department Outpatient Polyclinic, Ankara
      Training and Research Hospital. The patients' data (history, family history,
      neurological examination findings, echocardiography findings, and cerebral MRI
      findings) were retrospectively reviewed. RESULTS: Age, gender, body mass index,
      blood lipid level, migraine duration, localization of headache, average number of
      headache per month, medication for headache attack, and echocardiography findings
      were similar between the two groups. (p>0.05). CONCLUSION: In this study, we did
      not find any association between cardiovascular risk factors and WMHs development
      in patients with MWO. The association of risk factors other than cardiovascular
      risk factors (genetic factors and oxidative stress) with the development of WMHs
      in patients with MWO should also be studied in future.

PMID- 29171646
TI  - [Effect of rocuronium administration rate and remifentanil on prevention of
      rocuronium injection pain in pediatric cases].
AB  - OBJECTIVES: In this study, we aimed to determine the effect of remifentanil
      administration prior to slow and fast rocuronium infusion on hemodynamic changes
      and rocuronium injection pain in pediatric patients. METHODS: In total, 120 5-15
      year-old ASA score I/II pediatric patients were included in the study. Group A:
      slow rocuronium injection-saline; group B: slow rocuronium injection (0.6 mg/kg
      IV)-remifentanyl; group C: fast rocuronium injection-saline; and group D: fast
      rocuronium injection-remifentanyl. Withdrawal movement after rocuronium injection
      was recorded based on a 3-point response to withdrawal score. Hemodynamic
      parameters were recorded. RESULTS: One minute after rocuronium injection, HR
      values were found to be lower in remifentanil groups (p: 0.0001; 101.4+/-22.1, p:
      0.003; 99.8+/-18.3 in group B and D, respectively) compared with those in placebo
      groups (p: 0.025; 107.4+/-21.7, p: 0.012; 114.0+/-16.4 in group A and C,
      respectively). With respect to the response to withdrawal scores,
      unresponsiveness rates were the highest in group B (66.7%) and group D (70%). The
      number of non-responder patients was 9 in saline-administered groups (group A and
      C), whereas it was 20 and 21 in remifentanil-administered groups (group B and D,
      respectively). Generalized responses were observed predominantly in groups A
      (20%) and C (20%). Generalized responses were highest in groups A (20%, n=6) and
      C (20%, n=6). CONCLUSION: There was no impact of infusion speed on rocuronium
      injection pain in pediatric cases, whereas it is concluded that remifentanil
      administration prior to rocuronium injection considerably reduced rocuronium
      injection pain regardless of injection speed and without serious hemodynamic
      changes.

PMID- 29171647
TI  - Pain, anxiety, and depression during bone marrow aspiration and biopsy.
AB  - OBJECTIVES: This study is performed with the aim of prospectively analyzing the
      factors that affect pain, anxiety, and depression in cases for whom bone marrow
      aspiration and biopsy are performed and the relationships among them. METHODS:
      This study consisted of 90 patients who consulted to Department of Hematology,
      Faculty of Medicine, Uludag University, and followed-up for bone marrow
      aspiration and biopsy indication. The data was gathered using a personal
      information form, Hospital Anxiety Depression scale, and Wong-Baker face pain
      scale where generally face expressions exist. RESULTS: The average age of the
      patients who participated in the study was 50.90 years (16.59), and the pain
      level after the application was 1.98 (1.33). After the application, a positive
      relationship is determined between the pain level and anxiety (r=-0.79; p=0.02),
      whereas this has a negative relationship with age (r=0.78; p=0.03). CONCLUSION:
      As a result, pain develops depending on bone marrow aspiration and biopsy;
      therefore, taking precautions aimed at alleviating pain and evaluation of pain
      before and after the application within the scope of total maintenance have been
      suggested.

PMID- 29171648
TI  - Methemoglobinemia incidence after the application of lidocaine for small surgical
      procedures.
AB  - OBJECTIVES: Methemoglobinemia (MetHb) is a rare condition that may have mortal
      consequences. Literature shows cases of methemoglobinemia due to the use of
      lidocaine and other local anesthetics. This is a cross-sectional study to
      determine the incidence of methemoglobinemia after the application of lidocaine.
      METHODS: In this study, 88 patients admitted to the emergency department of a
      university hospital between May 2014 and May 2015 and needed lidocaine
      application for small surgical procedures were included. When compared before and
      after the administration of lidocaine <2 mg/kg and >2 mg/kg, there was not a
      significant difference in the level of methemoglobin, hemoglobin, or in the
      hematocrit (p=0.604, p=0.502, and p=0.367, respectively). RESULTS: Mean age of
      the patients was 33.85 (+/-17.58) years, and 83% of the patients were male.
      Methemoglobin levels were not significantly different before and after the
      procedures (p>0.05). CONCLUSION: The results of our study were consistent with
      the literature; lidocaine associated methemoglobinemia is a rare complication.

PMID- 29171649
TI  - [Cognitive behavioral therapy for tension-type headache: a case report].
AB  - Tension-type headache has a very high socioeconomic impact, and its lifetime
      prevalence is reported to be between 30% and 78% in different studies. It is
      widely acknowledged that noninvasive management with a multidisciplinary approach
      should be considered for the treatment of tension-type headache. Cognitive
      behavioral therapy and relaxation exercises are efficient techniques. This
      article illustrates the application of a cognitive behavioral therapy protocol
      enhanced with progressive muscle stretching and relaxation exercises in the
      treatment of chronic tension-type headache via a case report. Our patient had an
      ongoing headache for 6 years when he was referred to us by the department of
      psychiatry. After 10 cognitive behavioral therapy sessions, the patient had
      learned to notice muscle tension and relax the muscles as well as to recognize
      and express his emotions in a better way. He became aware of automatic thoughts
      and learned to find alternative thoughts. Headache severity decreased, and he was
      able to increase participation in daily life activities.

PMID- 29171650
TI  - [Contact lenses as a migraine trigger].
AB  - We aimed to investigate the relationship between contact lens (CL) usage and
      migraine attacks. Our patient who began using CL with different base curves
      experienced discomfort and burning of the eyes. The ocular complaints were
      followed by migraine attacks. The frequency of migraine attacks decreased
      significantly when the flatter base curve was selected. We assessed the potential
      causal relationship between CL and migraine.

PMID- 29171651
TI  - Pulmonary embolism occurring in a patient treated with spinal cord stimulation.
AB  - Spinal cord stimulation (SCS) has been shown to be an effective method for
      treating many chronic pain syndromes. In addition, providing pain relief with SCS
      can reduce immobilization and complications related to immobilization. The
      present case describes pulmonary embolism (PE) that occurred in patient being
      treated with SCS for post-laminectomy syndrome. The possibility of PE must be
      kept in mind while treating patients with SCS.

PMID- 29171652
TI  - Accidental intrathecal catheterization in two patients having undergone lumbar
      radiotherapy.

PMID- 29171653
TI  - Retrospective evaluation of the effects of periprostatic local anesthesia on
      recurrent prostate biopsy.
AB  - OBJECTIVES: The aim of the study was investigate the pain palliation effect of 2%
      dose of lidocaine on the periprostatic nerve block in prostate biopsy patients.
      METHODS: Extended (12 cores) and saturation (22 cores) biopsy patients were
      included. The patients were separated into three groups: extended biopsy patients
      (Group I), saturation biopsy patients (Group II), and control group patients
      undergoing a biopsy procedure for the first time (Group III). All patients
      received 2% lidocaine (10 mL) on both the seminal vesicular junction and apex of
      the prostate with transrectal ultrasonography guidance. Following the procedure,
      the pain levels of patients were assessed using a 10-cm linear Visual Analog
      Scale (VAS). RESULTS: Following the procedure, the VAS values of each group were
      2.96+/-1.06, 3.2+/-1.47, and 2.93+/-0.94, respectively (p>0.05). While the
      highest pain score was seen in the saturation group patients (II), the lowest
      pain level was seen in the control biopsy group (III). However, no statistical di
      erence was observed among the groups. CONCLUSION: Herein, we observed that a
      local injection using 2% lidocaine was effective as local anesthetic in recurrent
      prostate biopsies. In addition, it was found that the pain level increases as the
      number of cores taken in recurrent prostate biopsies increases; however, this has
      not been established statistically.

PMID- 29171654
TI  - Remodelling of collagen fibres in the placentas of women with venous
      insufficiency during pregnancy.
AB  - Haemodynamic changes produced during pregnancy lead to elevated venous pressure
      in the legs and an increased resting consumption of oxygen. These events can
      cause varicose veins, or venous insufficiency (VI), which by creating an
      environment of hypoxia could affect the structure and function of the placental
      barrier. This study assesses the remodelling state of the placental villi by
      examining differences in collagens with a known role in villus structure and in
      placental barrier permeability between patients with and without VI. Samples of
      67 placentas from women with VI (n=24) and without VI (n=43) during their
      pregnancy were processed for gene and protein expression analysis of COL-I, COL
      III, MMP-2 and MMP-9 by RT-qPCR and immunohistochemistry. While no differences in
      COL-I expression levels were detected in the samples from women with and without
      VI, significant differences did emerge in both gene and protein expression levels
      of COL-III. Importantly, COL-I/III ratios were reduced in the VI group compared
      to controls. MMP-2 activity was similar in the two groups while MMP-9 levels were
      significantly elevated in VI with greatest expression differences observed at the
      level of the decidual cells. Mothers who developed VI during pregnancy showed
      significantly higher COL-III and MMP-9 levels consistent with a state of
      remodelling of the placental villi.

PMID- 29171656
TI  - Investigation of the presence of HPV on KTP laser fibers following KTP laser
      treatment of papilloma.
AB  - OBJECTIVES: Recurrent respiratory papillomatosis is often treated with in-office
      laser procedures using a potassium titanyl phosphate (KTP) laser transmitted
      through a laser fiber. Although effective, this procedure has notable downsides,
      including the possibility of transmitting human papillomavirus (HPV) in the smoke
      plume and the high cost of these single-use fibers. The objective of this study
      is to determine if HPV can be detected on a laser fiber after use, with or
      without sterilization. METHODS: Twelve patients with laryngeal papillomas were
      treated with KTP laser energy transmitted via a KTP fiber. Ten fibers were
      sterilized in CIDEX (ASP, Irvine, California), a glutaraldehyde disinfectant, for
      12 minutes, whereas two fibers were left unsterilized. Human papillomavirus DNA
      amplification was done on all 12 fiber samples with real-time polymerase chain
      reaction (PCR) using general primer mediated 5+ and 6+. Human papillomavirus
      genotyping detection was done using type specific probes and/or Sanger
      sequencing. RESULTS: Over 27 strains of HPV were not detected on KTP fibers after
      use, with or without sterilization. CONCLUSION: Human papillomavirus was
      undetectable by PCR on KTP laser fibers that were sterilized or unsterilized
      after use. Further studies are needed utilizing a transmission model to determine
      if HPV can be incubated from this fiber after sterilization. LEVEL OF EVIDENCE:
      NA. Laryngoscope, 128:926-928, 2018.

PMID- 29171655
TI  - Oral sampling methods are associated with differences in immune marker
      concentrations.
AB  - OBJECTIVE: To determine whether the concentration and distribution of immune
      markers in paired oral samples were similar. STUDY TYPE: Clinical research. STUDY
      DESIGN: Cross-sectional study. METHODS: Paired saliva and oral secretions (OS)
      samples were collected. The concentration of immune markers was estimated using
      Luminex multiplex assay (Thermo Fisher Scientific, Waltham, MA). For each sample,
      the concentration of respective immune markers was normalized to total protein
      present and log-transformed. Median concentrations of immune markers were
      compared between both types of samples. Intermarker correlation in each sampling
      method and across sampling methods was evaluated. RESULTS: There were 90 study
      participants. Concentrations of immune markers in saliva samples were
      significantly different from concentrations in OS samples. Oral secretions
      samples showed higher concentrations of immunoregulatory markers, whereas the
      saliva samples contained proinflammatory markers in higher concentration.
      CONCLUSION: The immune marker profile in saliva samples is distinct from the
      immune marker profile in paired OS samples. LEVEL OF EVIDENCE: 2b. Laryngoscope,
      128:E214-E221, 2018.

PMID- 29171657
TI  - The parenthood argument.
AB  - Don Marquis is well known for his future like ours theory (FLO), according to
      which the killing beings like us is seriously morally wrong because it deprives
      us of a future we can value. According to Marquis, human fetuses possess a future
      they can come to value, and thus according to FLO have a right to life. Recently
      Mark Brown has argued that even if FLO shows fetuses have a right to life, it
      fails to show that fetuses have a right to use their mother's body, evoking
      Judith Jarvis Thomson's famous violinist case. In the wake of Brown's conclusion,
      Marquis presents a new argument-the parenthood argument (PA)-which he believes
      shows that abortion is seriously morally wrong. Here I argue that the PA fails to
      show abortion is seriously morally wrong for the same reasons FLO fails to show
      abortion is seriously morally wrong.

PMID- 29171658
TI  - Epistaxis in children and adolescents with hereditary hemorrhagic telangiectasia.
AB  - OBJECTIVES/HYPOTHESIS: Our objective was to describe epistaxis onset and severity
      in pediatric hereditary hemorrhagic telangiectasia (HHT) patients and study the
      cumulative incidence of epistaxis by age of onset within each genetic subtype.
      STUDY DESIGN: Retrospective cohort chart review. METHODS: Charts were reviewed of
      patients age 0 to 18 years with a clinical or genetic diagnosis of HHT who were
      evaluated at a tertiary multidisciplinary HHT clinic from January 2010 to June
      2016. The epistaxis severity score (ESS), a validated tool for assessing
      epistaxis severity, was used to assess epistaxis. Statistical analyses were
      conducted on the full HHT cohort as well as subgroups stratified by the HHT
      causative gene (HHT1 = ENG and HHT2 = ACVRL1). RESULTS: Sixty-nine pediatric
      subjects were identified; 60 had HHT confirmed by genetic testing, and nine (from
      families with known mutations) met published clinical diagnostic criteria alone.
      Fifty-nine (85%) had onset of epistaxis. The median age of onset of epistaxis was
      5 years (interquartile range [IQR]: 2-9 years). The median ESS for the entire
      cohort was 1.6 (IQR: 0-2.6). The median ESS was higher in HHT1 versus HHT2 (2.3
      vs. 1.1, P = .002), and age of epistaxis onset was earlier in HHT1 (3 vs. 5
      years, P = .03). Sex and age were not associated with ESS. CONCLUSIONS: Epistaxis
      may present early in HHT, but is typically mild in the pediatric period. Severity
      in the pediatric population is worse in patients with HHT1. By recognizing the
      significance of even mild, infrequent epistaxis in a child with a family history
      of HHT, and understanding that not all HHT patients have epistaxis during
      childhood, community providers and otolaryngologist can assist in the early
      detection of HHT. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:1714-1719, 2018.

PMID- 29171659
TI  - Conscientious objection, professional duty and compromise: A response to
      Savulescu and Schuklenk.
AB  - In a recent article in this journal, Savulescu and Schuklenk defend and extend
      their earlier arguments against a right to medical conscientious objection in
      response to criticisms raised by Cowley. I argue that while it would be
      preferable to be less accommodating of medical conscientious than many countries
      currently are, Savulescu and Schuklenk's argument that conscientious objection is
      'simply unprofessional' is mistaken. The professional duties of doctors should be
      defined in relation to the interests of patients and society, and for reasons set
      out in this article, these may support limited accommodation of conscientious
      objection on condition that it does not impede access to services. Moreover, the
      fact that conscientious objection appears to involve unjustifiable compromise
      from the objector's point of view is not a reason for society not to offer that
      compromise. Arguing for robust enforcement of the no-impediment condition, rather
      than opposing conscientious objection in principle, may be a more effective way
      of addressing the harms resulting from an over-permissive conscientious objection
      policy.

PMID- 29171661
TI  - A randomised controlled trial comparing high-flow nasal oxygen with standard
      management for conscious sedation during bronchoscopy.
AB  - Traditional conscious sedation for endobronchial ultrasound procedures places
      patients at risk of desaturation, and high-flow nasal oxygen may reduce the risk.
      We designed a parallel-group randomised controlled trial of high-flow nasal
      oxygen at a flow rate of 30-70 l.min-1 via nasal cannulae, compared with standard
      oxygen therapy at 10 l.min-1 via a bite block in adults planned for conscious
      sedation for endobronchial ultrasound. The primary outcome was the proportion of
      patients experiencing desaturation (defined as SpO2 < 90%). Secondary outcomes
      included oxygen saturation after pre-oxygenation, lowest oxygen saturation during
      procedure, number of hypoxic episodes, duration of hypoxia, end-procedure end
      tidal CO2 , satisfaction scores and complications. Thirty participants were
      allocated to each group. Baseline patient characteristics, procedure time and
      anaesthetic agents used were similar between the groups. Desaturation occurred in
      4 out of 30 patients allocated to the high-flow nasal oxygen group, compared with
      10 out of 30 allocated to the standard oxygenation group, a non-significant
      difference (p = 0.07) with intention to treat analysis. The difference was
      significant (p = 0.047) when using a per-protocol analysis. Oxygen saturation
      after pre-oxygenation and the lowest oxygen saturation during procedure were
      significantly higher in the high-flow nasal oxygen group compared with the
      standard oxygenation group; median (IQR [range] 100 (99-100 [93-100]) vs. 98 (97
      99 [94-100]), p = 0.0001 and 97.5 (94-99 [77-100]) vs. 92 (88-95 [79-98]), p <
      0.001, respectively. There were no differences in other secondary outcomes.
      Although high-flow nasal oxygen may prevent desaturation due to some causes, it
      does not protect against hypoxaemia in all circumstances.

PMID- 29171660
TI  - Relationship between degree of obstruction and airflow limitation in subglottic
      stenosis.
AB  - OBJECTIVES: Subglottic stenosis (SGS) is one of the most common airway disorders
      in pediatric patients. Currently, treatment decisions rely primarily on the
      Cotton-Myer scale, which classifies SGS severity based on percentage reduction in
      airspace cross-sectional area (CSA). However, the precise relationship between
      upper airway resistance and subglottic CSA is unknown. We hypothesize that airway
      resistance can be described by the Bernoulli Obstruction Theory, which predicts
      that airway resistance is inversely proportional to airspace CSA ( R?A-1) in
      cases of severe constriction. METHODS: Computed tomography (CT) scans of six
      healthy subjects and five SGS patients were used to create three-dimensional
      models of the respiratory tract from nostrils to carina. Cylindrical segments of
      varying lengths and varying diameters were digitally inserted in the subglottis
      of the healthy subjects to create simulated SGS models. Computational fluid
      dynamics simulations were run, and airway resistance was computed in the
      simulated SGS models and actual SGS models. RESULTS: Constriction diameter had a
      greater impact in airway resistance than constriction length. In agreement with
      the Bernoulli Obstruction Theory, airway resistance in the simulated SGS models
      was well represented by the power law R=aAb, where a is a constant and the
      exponent b ranged from -0.85 to -1.07. The percentage reduction in airflow
      (QOBSTRUCTIONQHEALTHY) at a constant pressure drop was found to be directly
      proportional to the percentage reduction in CSA (AOBSTRUCTIONAHEALTHY) in the
      limit of severe constrictions, namely QOBSTRUCTIONQHEALTHY=kAOBSTRUCTIONAHEALTHY,
      where k=2.25 +/- 0.15. Airway resistances in the simulated SGS models were
      similar to resistances in models based on CT scans of actual SGS patients,
      suggesting that our simulated SGS models were representative of airway resistance
      in actual SGS patients. CONCLUSION: Our computer simulations suggest that the
      degree of airflow limitation in SGS patients may be estimated based on anatomic
      measurements alone. Future studies are recommended to test these predictions in
      larger cohorts. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1551-1557, 2018.

PMID- 29171662
TI  - A Within-Family Examination of Interparental Conflict, Cognitive Appraisals, and
      Adolescent Mood and Well-Being.
AB  - Interparental conflict (IPC) is a well-established risk factor across child and
      adolescent development. This study disentangled situational (within-family) and
      global (between-family) appraisal processes to better map hypothesized processes
      to adolescents' experiences in the family. This 21-day daily dairy study sampled
      151 caregivers and their adolescents (61.5% female). Using multilevel mediation
      analyses indicated that, on days when IPC was elevated, adolescents experienced
      more threat and self-blame. In turn, when adolescents experienced more threat
      appraisals, they experienced diminished positive well-being; whereas days when
      adolescents felt more self-blame, they experienced increased negative mood and
      diminished positive well-being. Statistically significant indirect effects were
      found for threat as a mediator of IPC and positive outcomes. Daily blame
      appraisals mediated IPC and adolescent angry mood.

PMID- 29171663
TI  - Granulocytic anaplasmosis in 63 dogs: clinical signs, laboratory results, therapy
      and course of disease.
AB  - OBJECTIVES: To describe the clinical signs, laboratory results, therapy and
      course of disease in dogs with canine granulocytic anaplasmosis in which co
      infections had been excluded. METHODS: Medical records of dogs naturally infected
      with Anaplasma phagocytophilum were retrospectively evaluated with regard to
      clinical signs and laboratory abnormalities at the time of presentation, therapy
      and course of disease. RESULTS: Nine hundred and seventy-four dogs with clinical
      signs suspicious for canine granulocytic anaplasmosis were tested for A.
      phagocytophilum DNA by modified real-time PCR; 72 dogs had a positive result.
      Nine of the positive dogs were excluded from further evaluation due to other
      diseases or lack of data. The most common clinical signs in the 63 A.
      phagocytophilum-positive dogs included in the study were lethargy and reduced
      activity (83%), fever (67%) and inappetence (63%). Thrombocytopenia was the most
      common laboratory abnormality (86%), followed by increased liver enzyme
      activities and hyperbilirubinaemia (77%), anaemia (70%), hypoalbuminaemia (62%)
      and leucocytosis (27%). Of 36 thrombocytopenic dogs tested for platelet-bound
      antibodies, 44% were positive. Of the 63 infected dogs, 59 (97%) recovered, two
      dogs died (epileptic seizures and immune-mediated haemolytic anaemia) and two
      were lost to follow-up. CLINICAL SIGNIFICANCE: In areas where it is endemic,
      canine granulocytic anaplasmosis should be considered as a potential cause of
      acute nonspecific clinical signs or immune-mediated disease if tick exposure
      cannot be excluded.

PMID- 29171664
TI  - Does water fluoridation affect the prevalence of enamel fluorosis differently
      among racial and ethnic groups?
AB  - OBJECTIVES: There are reports showing higher prevalence of enamel fluorosis among
      African-American children. This study was conducted to assess whether the effect
      of water fluoride level on enamel fluorosis is different among different
      race/ethnicity groups among US school children. METHODS: Data from the National
      Survey of Oral Health of US School Children 1986-1987 were analyzed to determine
      the prevalence of enamel fluorosis among 7-17 year-old children. The association
      between race/ethnicity and enamel fluorosis was examined using logistic
      regression modeling after controlling for potential confounders age, gender,
      water fluoridation, other sources of fluoride, and region of residence. RESULTS:
      The prevalence of very mild to severe enamel fluorosis was 20.8 (95% CI, 15.4,
      26.3) and 25.7 (95% CI, 15.0, 36.5) percent among non-Hispanic White and non
      Hispanic Black children, respectively. Neither the adjusted odds ratio of 1.3
      (0.8, 2.0) for the non-Hispanic Black group nor the interaction effect between
      non-Hispanic Black and water fluoridation were statistically significant.
      CONCLUSIONS: Enamel fluorosis was not associated with race/ethnicity. Our
      analysis suggests that exposure to similar levels of fluoride in the water does
      not appear to place certain race/ethnic groups at a higher risk for developing
      enamel fluorosis, and lowering the optimal range of drinking water fluoride to a
      single value of 0.7 ppm will provide a level of protection against enamel
      fluorosis that will benefit all race/ethnicity groups.

PMID- 29171665
TI  - Bypassing the barrier: new routes for delivery of macromolecules to the central
      nervous system.

PMID- 29171666
TI  - The association between paternal depressogenic cognitive styles during pregnancy
      and offspring depressogenic cognitive styles: an 18-year prospective cohort
      study.
AB  - BACKGROUND: Preventing the development of depressogenic or negative cognitive
      styles could also prevent the development of depression, a leading public health
      problem worldwide. Maternal negative cognitive styles are a modifiable risk
      factor for the development of negative cognitive styles in offspring. However,
      evidence on the role of paternal negative cognitive styles is inconclusive and
      there have only been a few small studies, which may also have lacked statistical
      power. METHODS: We used data from the Avon Longitudinal Study of Parents and
      Children (ALSPAC) to investigate the association between paternal negative
      cognitive styles, measured when mothers were 18 weeks pregnant, and offspring
      negative cognitive styles 18 years later (N = 6,123). Associations were
      calculated using linear regression models, before and after adjustment for
      confounders including maternal negative cognitive styles. We compared
      associations before and after controlling for depression in parents and
      offspring, and used multiple imputation to reduce biases that may have arisen due
      to missing data. RESULTS: A two-standard deviation increase in paternal negative
      cognitive style was associated with a 3-point increase in offspring negative
      cognitive style (95% CI 1.36-4.37). This association remained after adjustment
      for confounders and was independent of depression in both parents and offspring.
      The effect size was equivalent to that of maternal negative cognitive style, and
      was also independent of maternal negative cognitive style. CONCLUSIONS: Our
      results suggest that fathers should be included in individual- and family-based
      interventions designed to prevent the development of depressogenic cognitive
      styles in adolescent offspring. This could possibly also prevent the development
      of depression.

PMID- 29171667
TI  - Exposure to Parental Depression in Adolescence and Risk for Metabolic Syndrome in
      Adulthood.
AB  - The psychosocial consequences of living with a depressed parent have been well
      characterized. Less well known, however, is how this exposure is predictive of
      later physical health problems. The present study evaluated how parental
      depression across youths' adolescence (ages 11-18) was associated with youth
      metabolic syndrome at age 25 (n = 391). Youth self-regulation and health
      behaviors were considered as possible moderators of the link between parental
      depression and youth metabolic syndrome. Analyses revealed that parental
      depression in adolescence was associated with a composite score reflecting
      metabolic syndrome components in early adulthood. Furthermore, self-regulation
      and health behaviors moderated this link, such that links between parental
      depression and the metabolic syndrome existed only for youth with low self
      regulation or unhealthy behaviors.

PMID- 29171668
TI  - Post-temporary ligation intraoperative mesenteric portovenography: comparison
      with CT angiography for investigation of portosystemic shunts.
AB  - OBJECTIVES: Comparison of pre-operative CT angiography and post-temporary, full
      ligation, intraoperative, mesenteric portovenography for the characterisation of
      intrahepatic portal vasculature in patients with single extrahepatic
      portosystemic shunts. METHODS: Descriptive analysis of previously collected
      images from 14 dogs and five cats. RESULTS: With the exception of shunts
      involving the right gastric vein, intrahepatic arborisation appeared similar on
      both modalities. Portovenography improved contrast enhancement and slightly
      enlarged the intrahepatic portal vasculature. CLINICAL SIGNIFICANCE: CT
      angiography cannot replace intraoperative mesenteric portovenography after
      temporary full ligation, which provides information on intrahepatic portal
      vascularity. It is a practical and dynamic procedure, providing results that are
      instantaneously available at the time of surgery. In addition, intraoperative
      post-temporary, full-ligation, mesenteric portography confirmed that the single
      shunting vessel had both been recognised and ligated.

PMID- 29171669
TI  - Volume responsiveness assessed by passive leg raising and a fluid challenge: a
      critical review focused on mean systemic filling pressure.
AB  - This review applied cardiovascular principles relevant to the physiology of
      venous return in interpreting studies on the utility of a passive leg-raising
      manoeuvre to identify patients who do (responders) or do not respond to a
      subsequent intravenous volume challenge with an increase in cardiac output.
      Values for cardiac output, mean arterial and central venous pressure, and the
      calculated cardiovascular variables mean systemic filling pressure analogue,
      heart efficiency, cardiac power indexed by volume state and volume efficiency,
      before and after passive leg raising as well as before and after fluid volume
      challenge, were extracted from published studies. Eleven studies including 572
      patients and 52% responders were analysed. Cardiac output increased by 12% in
      responders during passive leg raising and by 22% following a volume challenge. No
      statistically significant differences were found between responders and non
      responders in cardiac output, mean arterial or central venous pressure before the
      passive leg-raising manoeuvre or the volume challenge. In contrast, the
      calculated mean (SD) systemic filling pressure analogue, reflecting the
      intravascular volume, was significantly lower in responders (14.2 (1.8) mmHg)
      than non-responders (17.5 (3.4) mmHg; p = 0.007) before the passive leg-raising
      manoeuvre, as well as before fluid volume challenge (14.6 (2.2) mmHg vs. 17.6
      (3.5) mmHg, respectively; p = 0.02). The scalar measure volume efficiency was
      higher in responders at 0.35 compared with non-responders at 0.10. Non-responders
      also demonstrated deteriorating heart efficiency of -15% and cardiac power of -7%
      when given an intravenous fluid volume challenge. The results demonstrate that
      the calculation of mean systemic filling pressure analogue and derived variables
      can identify patients likely to respond to a fluid volume challenge and provides
      scalar results rather than merely a dichotomous outcome of responder or non
      responder.

PMID- 29171670
TI  - Potential treatment for vocal fold scar with pirfenidone.
AB  - OBJECTIVES/HYPOTHESIS: Pirfenidone (PFD) is a strong antifibrotic agent that has
      been clinically approved in Japan for idiopathic pulmonary fibrosis. We examined
      the antifibrotic effects of PFD on fibroblasts isolated from scarred vocal folds
      (VFs) of ferrets in vitro. STUDY DESIGN: Prospective animal experiments with
      controls. METHODS: Scar fibroblasts (SFs) were isolated from scarred VFs that had
      been electrocauterized 2 weeks before harvesting (N = 4). Normal fibroblasts
      (NFs) were isolated from intact VFs (N = 4). SFs and NFs were incubated in the
      presence of 10 ng/mL transforming growth factor beta1 (TGF-beta1), with or
      without PFD. After the 48-hour incubation, mRNA expression levels of alpha smooth
      muscle actin (alphaSMA), TGF-beta1, collagen type I, and hyaluronan synthase 2
      (HAS2) were examined by real-time polymerase chain reaction. Immunohistochemistry
      with anti-alphaSMA anti-collagen type I and phosphorylated Smad (p-Smad)2/3
      antibodies in SFs with or without PFD was performed. SFs and NFs were cultured in
      collagen gel with or without PFD for 48 hours, and the extent of gel contraction
      was examined quantitatively. RESULTS: PFD treatment significantly (P < .05)
      decreased mRNA expression of collagen type I, significantly increased mRNA
      expression of TGF-beta1 and HAS2, and significantly suppressed collagen gel
      contraction. However, it did not have a significant effect on the expression of
      alphaSMA. The expression of p-Smad2/3 in the nucleus was faded with PFD, possibly
      demonstrating the suppression of translocation of p-Smad2/3 from cytoplasm to
      nucleus with PFD. CONCLUSIONS: This is the first report to demonstrate the in
      vitro antifibrotic effects of PFD on fibroblasts isolated from scarred VFs of
      ferrets. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E171-E177, 2018.

PMID- 29171671
TI  - Meta-analysis of induction chemotherapy as a selection marker for chemoradiation
      in the head and neck.
AB  - OBJECTIVE: Many trials incorporate induction chemotherapy (IC) in selecting for
      organ preservation in head and neck squamous cell carcinomas (HNSCC). However,
      few studies examine IC response in predicting for chemoradiation therapy (CRT)
      response. This meta-analysis aims to determine the predictive accuracy of IC for
      subsequent response to CRT and overall survival (OS). DATA SOURCES: Medline,
      EMBASE, Cochrane register. METHODS: A systematic search identified studies from
      database inception to October 2016 that used IC prior to CRT as definitive
      treatment for advanced HNSCC. The sensitivities and specificities of IC response
      predicting for complete CRT response were calculated, and the results were pooled
      in a summary receiver operating curve. One-, 2- and 5-year OS data were
      extracted. RESULTS: Seven studies (n = 423 patients) were analyzed for response
      and six (n = 439) for OS. Pooled median sensitivity and specificity of IC
      response predicting CRT response were 0.95 (95% confidence interval [CI]: 0.72
      0.98) and 0.43 (95% CI: 0.00-0.61), respectively. Patients were more likely to
      respond to CRT given previous response to IC (positive likelihood ratio = 1.6;
      95% CI: 1.21-2.11) and less likely to respond to CRT if they failed to respond to
      IC (negative likelihood ratio = 0.16; 95% CI: 0.07-0.38). At 2 years, good
      response to IC was a statistically significant prognostic marker with a risk
      ratio of 1.35 (95% CI: 1.12-1.64). CONCLUSION: Our data suggests that patients
      with poor IC response will have poorer response to CRT and should be directed to
      other modalities. In contrast, good IC response does not guarantee a favorable
      outcome to CRT; however, because these patients are likely to have better
      prognoses, they should be offered salvage therapies of curative intent despite
      treatment failure. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1594-1601, 2018.

PMID- 29171672
TI  - Teaching frontal sinus anatomy using the frontal sinus masterclass 3- D
      conceptualization model.
AB  - OBJECTIVE: Frontal sinus anatomy is complex and often is a difficult subject to
      both teach and learn. The traditional surgical dogma of "see one, do one, teach
      one" is impractical and dangerous in the frontal sinus. Based on the building
      block three-dimensional conceptualization module, the Frontal Sinus Masterclass
      (FSMC) was created to teach this anatomy. METHODS: Study was performed at two
      academic centers among second- to fifth-year otolaryngology residents. A pretest
      assessed knowledge prior to the course. Computed tomography scans of the sinuses
      were evaluated in triplanar view, and participants attempted to reconstruct the
      anatomy. Subsequently, the course instructor explained the anatomy using the
      building block method and showed a short video of the surgical dissection,
      pointing out relevant anatomy. Cases progressed in anatomical difficulty and
      inflammatory load. A posttest determined knowledge after the course. RESULTS:
      Thirty of 50 participating residents completed the pre- and posttests (14 junior,
      16 senior residents). Correct identification of the frontal sinus drainage
      pathway increased from 42% to 63% correct (P = 0.054). Anatomical assessment
      increased from 61% to 68% correct (P = 0.047), and overall assessment increased
      from 52% to 66% correct (P = 0.016). CONCLUSION: Objectively, participants of the
      FSMC expanded on their ability to recognize cells of the frontal recess on CT
      scans. Before the class, residents could answer less than half of the answers
      correctly, and by the end of the class they were answering over two-thirds of
      these complex questions correctly. Subjectively, participants reported benefit
      from the course and felt they would be better surgeons. LEVEL OF EVIDENCE: NA.
      Laryngoscope, 128:1294-1298, 2018.

PMID- 29171673
TI  - Does the diameter of the stapes prosthesis really matter? A prospective clinical
      study.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the influence of the diameter of stapes
      prosthesis on functional outcomes in stapes surgery. STUDY DESIGN: Prospective
      cohort study. METHODS: Fifty consecutive small fenestra stapedotomies performed
      using a 0.4-mm-diameter prosthesis were compared with 50 consecutive small
      fenestra stapedotomies carried out using a 0.6-mm-diameter piston. Audiological
      assessment following the recommendations of the Committee on Hearing and
      Equilibrium was performed 1 month after surgery. Postoperative complications
      between the two groups were noted. RESULTS: There were no statistically
      significant differences in demographic data between the two groups, and no
      differences in preoperative bone-conduction (BC) or air-conduction (AC) hearing
      thresholds for all frequencies (analysis of variance [ANOVA] and chi2 tests). No
      differences were found in the mean preoperative BC and AC pure-tone average and
      air-bone gap (ABG). In the postoperative evaluation, a statistically significant
      difference was found for the mean AC gain (20 +/- 8.7 vs. 24 +/- 11.5, P = .042,
      ANOVA) as well as for the postoperative AC threshold at 0.125 and 0.25 kHz and
      the postoperative BC threshold at 0.25 kHz (P < .01, ANOVA). A postoperative ABG
      <=10 dB was obtained in 90% and 94% of patients in the 0.4-mm- and 0.6-mm
      diameter piston groups, respectively (difference not significant, chi2 test). No
      postoperative dead ear and/or sensorineural hearing loss was noted in either
      group. CONCLUSIONS: The 0.6-mm piston allowed a statistically significant higher
      AC gain compared with the 0.4-mm diameter piston. A larger diameter piston may be
      preferable if there are no anatomical or technical reasons that would favor a
      smaller prosthesis. LEVEL OF EVIDENCE: 2b Laryngoscope, 1922-1926, 2018.

PMID- 29171674
TI  - A dubious defense of 'after-birth abortion': A reply to Rasanen.
AB  - Scholars have offered various critiques of Alberto Giubilini and Francesca
      Minerva's controversial article, 'After-birth abortion: Why should the baby
      live?' My book The Ethics of Abortion: Women's Rights, Human Life, and the
      Question of Justice presents four such critiques. First, Giubilini and Minerva
      argue from the deeply controversial to the even more controversial. Second, they
      presuppose a false view of personal identity called body-self dualism. Third,
      their view cannot secure human equality. And fourth, their account of harm cannot
      account for harm found in some cases of murder. In the article, 'Pro-life
      arguments against infanticide and why they are not convincing', J. Rasanen
      examines and finds wanting these four critiques. This essay responds to Rasanen's
      defense of infanticide and argues that his responses to the four objections fail.

PMID- 29171675
TI  - Judgments of moral responsibility in tissue donation cases.
AB  - If a person requires an organ or tissue donation to survive, many philosophers
      argue that whatever moral responsibility a biological relative may have to donate
      to the person in need will be grounded at least partially, if not entirely, in
      biological relations the potential donor bears to the recipient. We contend that
      such views ignore the role that a potential donor's unique ability to help the
      person in need plays in underwriting such judgments. If, for example, a sperm
      donor is judged to have a significant moral responsibility to donate tissue to a
      child conceived with his sperm, we think this will not be due to the fact that
      the donor stands in a close biological relationship to the recipient. Rather, we
      think such judgments will largely be grounded in the presumed unique ability of
      the sperm donor to help the child due to the compatibility of his tissues and
      organs with those of the recipient. In this paper, we report the results of two
      studies designed to investigate the comparative roles that biological relatedness
      and unique ability play in generating judgments of moral responsibility in tissue
      donation cases. We found that biologically related individuals are deemed to have
      a significant moral responsibility to donate tissue only when they are one of a
      small number of people who have the capacity to help.

PMID- 29171676
TI  - Tween Television and Peers: Reinforcing Social Agents in Early Adolescents' Body
      Surveillance and Self-Objectification.
AB  - Sociocultural models of body image posit that the media and peers play a role in
      early adolescents' body dissatisfaction. Introducing a sociocultural perspective
      on youth sexualization, the present three-wave panel study (N = 968, Mage  =
      11.30) sought to examine the role of tween television and peer appearance
      conversations in early adolescents' body surveillance and self-objectification
      over time. Special attention was given to the mediating role of media
      internalization in these relationships. The results showed evidence for a
      reciprocal interaction between media internalization and peer appearance
      conversations and identified this reciprocal interaction as the underlying
      mechanism linking tween television exposure to higher levels of body surveillance
      and self-objectification 1 year later. Implications for body image and media
      literacy programs are discussed.

PMID- 29171677
TI  - Acute Kidney Injury with consumption of raw gall bladder of Indian carp fish
      (Labeo rohita): A single center study from India.
AB  - AIM: This retrospective study examined the clinical presentation and outcome of
      all patients who presented with acute kidney injury (AKI) following consumption
      of uncooked fish gallbladder as folk medicine. METHODS: We reviewed all cases
      admitted at our institute between 1st January 1997 and 31st December 2016
      following ingestion of fish gallbladder (Indian carp/Labeo rohita). RESULTS: A
      total 32 of patients were included, with a male: female ratio of 3:1 and mean age
      44.34 +/- 13.33 years. The mean number of gall bladder consumed was 4.59+/-4.75.
      All 32 patients presented with hepatic and renal failure. The mean duration of
      onset of symptoms following ingestion was 6.47+/-2.84 hours. At the time of
      admission, urine output was 187.9+/-141 ml/24 hours, serum creatinine 11.66+/
      2.50 mg/dl, serum bilirubin 6.14+/-3.91 mg/dl, SGPT 687+/-458 IU/L and SGOT 188+/
      181 IU/L. All but one patient required hemodialysis. Twenty-seven patients were
      discharged with recovering acute kidney injury while 5 patients died. Mean
      duration of hospital stay was 12.94+/-8.31 days. Mean number of hemodialysis
      received by patients was 4.59+/-3.12. Interval between consumption and onset of
      symptoms, serum bilirubin and SGPT were found to be significantly different
      between those who survived and died. CONCLUSION: AKI associated with ingestion of
      raw fish gallbladder is associated with significant morbidity and mortality.

PMID- 29171678
TI  - Visibility and meanings of partnership in health care for older people who need
      support to live at home.
AB  - INTRODUCTION: Problems experienced by older people with complex needs to live at
      home have been reported in the literature. This qualitative study builds on
      previous research and investigates enduring issues older people face when
      interacting with healthcare services. AIM: To gain an in-depth understanding of
      what is involved in providing good quality health care for older people who need
      support to live at home. METHODOLOGICAL DESIGN: We adopted an interpretive
      descriptive approach and conducted semi-structured interviews with older people
      (n = 7), carers (n = 8) and key informants (n = 11). Initial and secondary
      analysis of qualitative data was completed. FINDINGS: Major themes emerged about
      meanings of partnership in health care, and invisibility of the older person as a
      partner in health care. Partnership in health care was understood to mean being
      treated as an equal, being involved in decision-making, and making contributions
      which impact on health care and health systems. The metaphorical concept of
      'invisibility' related to the older person not being seen and heard as a partner
      in health care, as well as being a recipient of care. CONCLUSIONS: We concluded
      that older people who need support to live at home are not highly visible to
      health providers, policymakers and researchers as a central partner and consumer
      to be meaningfully engaged in shaping their health care. Opportunities to address
      persistent issues with quality of health care may in future be achieved through
      stronger partnerships between older people and health providers, to find new ways
      to improve the quality of care for older people.

PMID- 29171679
TI  - Self-Assembled Hybrid Materials Based on Organic Nanocrystals and Carbon
      Nanotubes.
AB  - Organic crystalline materials are used as dyes/pigments, pharmaceuticals, and
      active components of photonic and electronic devices. There is great interest in
      integrating organic crystals with inorganic and carbon nanomaterials to create
      nanocomposites with enhanced properties. Such efforts are hampered by the
      difficulties in interfacing organic crystals with dissimilar materials. Here, an
      approach that employs organic nanocrystallization is presented to fabricate
      solution-processed organic nanocrystal/carbon nanotube (ONC/CNT) hybrid materials
      based on readily available organic dyes (perylene diimides (PDIs)) and carbon
      nanotubes. The hybrids are prepared by self-assembly in aqueous media to afford
      free-standing films with tunable CNT content. These exhibit excellent
      conductivities (as high as 5.78 +/- 0.56 S m-1 ), and high thermal stability that
      are superior to common polymer/CNT hybrids. The color of the hybrids can be tuned
      by adding various PDI derivatives. ONC/CNT hybrids represent a novel class of
      nanocomposites, applicable as optoelectronic and conductive colorant materials.

PMID- 29171680
TI  - An Efficient Protocol to Synthesize N-Acyl-enamides and -Imines by Pd-Catalyzed
      Carbonylations.
AB  - For the first time, the bidentate phosphinite ligand 1,2-bis(di-tert
      butylphosphinoxy)ethane (tBu2 POCH2 CH2 OPtBu2 ) was synthesized. In the presence
      of this ligand, various N-acyl enamides were obtained in good yields and
      chemoselectivity by Pd-catalyzed carbonylation reaction of imines containing
      alpha-H. Meanwhile, imines without alpha-H could be transformed to N-acyl imines,
      which form highly hindered amides by straightforward addition of Grignard
      reagents.

PMID- 29171681
TI  - Spatial Patterning of Hydrogels via 3D Covalent Transfer Stamping from a Fugitive
      Ink.
AB  - In this study, a novel hydrogel patterning approach using 3D covalent transfer
      stamping from a fugitive ink is introduced. A model transfer molecule (7
      diethylamino-3-(4'maleimidylphenyl)-4-methylcoumarin (CPM)) is absorbed into a 3D
      fugitive ink stamp made from poly(caprolactone), and then encapsulated in a
      poly(ethylene glycol) hydrogel. As the CPM diffuses from the fugitive ink to the
      curing hydrogel it is selectively covalently bound at the boundary of the ink and
      the hydrogel. Removal of the fugitive ink by solvent exchange leads to a negative
      copy of interconnected channels patterned with the localized transfer of the
      molecules at the hydrogel interface. The results suggest that small molecules can
      be patterned in porous hydrogels in a spatially controllable manner and that the
      transferred amount can be tuned.

PMID- 29171682
TI  - In-hospital outcomes of transcatheter versus surgical aortic valve replacement in
      end stage renal disease.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative to
      surgical aortic valve replacement (SAVR) for patients with severe symptomatic
      aortic stenosis (AS) who are at intermediate and high risk for surgery.
      Commercial use of TAVR has expanded to patients with end stage renal disease
      (ESRD). OBJECTIVES: Compare in-hospital outcomes of TAVR versus SAVR in ESRD
      patients requiring hemodialysis (HD). METHODS: ESRD patients on HD undergoing
      TAVR (n = 328) or SAVR (n = 697) between 2012 and 2014 were identified in the
      National Inpatient Sample (NIS). Propensity-score matching method was used to
      minimize selection bias. Baseline characteristics and in-hospital outcomes were
      compared. RESULTS: TAVR patients were older (75.3 vs. 61.6 years, P < 0.001) and
      had more comorbidities, including congestive heart failure (16.2% vs. 7.5%),
      diabetes mellitus (28.4% vs. 22.5%), chronic lung disease (27.7% vs. 20.4%), and
      peripheral vascular disease (35.1% vs. 21.2%). Propensity-score matching yielded
      175 pairs of patients matched on 30 baseline covariates. Overall in-hospital
      mortality was high (9.9%) and similar between TAVR and SAVR (8% vs. 10.3%, P =
      0.58). TAVR was associated with shorter length of stay (LOS) (8 vs. 14 days, P <
      0.001), lower hospitalization cost ($276,448 vs. $364,280, P = 0.01), lower in
      hospital complications (60.6% vs. 76%, P = 0.003), and higher rate of home
      discharge (31.4% vs. 17.7%, P = 0.004) compared with SAVR. CONCLUSIONS:
      Regardless of treatment modality, patients with AS on HD have high in-hospital
      mortality. TAVR and SAVR have comparable in-hospital mortality in this
      population. However, TAVR is associated with shorter LOS, lower hospitalization
      costs, lower in-hospital complications, and higher rates of home discharge.

PMID- 29171683
TI  - Ptychographic X-Ray Imaging of Colloidal Crystals.
AB  - Ptychographic coherent X-ray imaging is applied to obtain a projection of the
      electron density of colloidal crystals, which are promising nanoscale materials
      for optoelectronic applications and important model systems. Using the incident X
      ray wavefield reconstructed by mixed states approach, a high resolution and high
      contrast image of the colloidal crystal structure is obtained by ptychography.
      The reconstructed colloidal crystal reveals domain structure with an average
      domain size of about 2 um. Comparison of the domains formed by the basic close
      packed structures, allows us to conclude on the absence of pure hexagonal close
      packed domains and confirms the presence of random hexagonal close-packed layers
      with predominantly face-centered cubic structure within the analyzed part of the
      colloidal crystal film. The ptychography reconstruction shows that the final
      structure is complicated and may contain partial dislocations leading to a
      variation of the stacking sequence in the lateral direction. As such in this
      work, X-ray ptychography is extended to high resolution imaging of crystalline
      samples.

PMID- 29171684
TI  - Comparison of left atrial pressure monitoring with dedicated catheter versus
      steerable guiding catheter during transcatheter mitral valve repair.
AB  - OBJECTIVE: The objective of this study was to determine the accuracy of left
      atrial pressure (LAP) measurement through the manufacturer provided steerable
      guiding catheter (SGC) during transcatheter mitral valve repair (TMVR).
      BACKGROUND: LAP measurement during TMVR has been shown to be associated with
      clinical improvement when measured through a dedicated catheter. METHODS:
      Simultaneous LAP was performed in consecutive patients using an independent fluid
      filled 4F multipurpose catheter and compared to LAP waveforms measured through
      the manufacturer-provided MitraClip SGC during TMVR (Abbott, Santa Clara, CA).
      RESULTS: Mean age of 10 consecutive subjects with primary mitral regurgitation
      undergoing TMVR was 83 +/- 3 years (60% female). Left atrial v wave and mean
      pressures through the dedicated catheter were 42 +/- 7 and 24 +/- 3 mmHg vs. 35
      +/- 7 and 23 +/- 3 mmHg through the SGC (P < 0.001 and P = 0.23, respectively).
      Mean differences in v wave and mean LAP were 8 +/- 4 and 1.0 +/- 2.4 mmHg
      (percent difference 19 and 3%), respectively. SGC waveform overdamping was
      observed in all cases. CONCLUSIONS: Left atrial v wave pressure measurement
      through a dedicated catheter with sideholes during TMVR has superior accuracy
      compared to the manufacturer provided SGC, which results in waveform overdamping
      and a significant underestimation of v wave pressure. These data have important
      implications for clinical practice.

PMID- 29171685
TI  - SLC6A3 polymorphism and response to methylphenidate in children with ADHD: A
      systematic review and meta-analysis.
AB  - Methylphenidate (MPH) is the most commonly used treatment for attention-deficit
      hyperactivity disorder (ADHD) in children. However, the response to MPH is not
      similar in all patients. This meta-analysis investigated the potential role of
      SLC6A3 polymorphisms in response to MPH in children with ADHD. Clinical trials or
      naturalistic studies were selected from electronic databases. A meta-analysis was
      conducted using a random-effects model. Cohen's d effect size and 95% confidence
      intervals (CIs) were determined. Sensitivity analysis and meta-regression were
      performed. Q-statistic and Egger's tests were conducted to evaluate heterogeneity
      and publication bias, respectively. The Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) system was used to assess the quality of
      evidence. Sixteen studies with follow-up periods of 1-28 weeks were eligible. The
      mean treatment acceptability of MPH was 97.2%. In contrast to clinical trials,
      the meta-analysis of naturalistic studies indicated that children without 10/10
      repeat carriers had better response to MPH (Cohen's d: -0.09 and 0.44,
      respectively). The 9/9 repeat polymorphism had no effect on the response rate
      (Cohen's d: -0.43). In the meta-regression, a significant association was
      observed between baseline severity of ADHD, MPH dosage, and combined type of ADHD
      in some genetic models. Sensitivity analysis indicated the robustness of our
      findings. No publication bias was observed in our meta-analysis. The GRADE
      evaluations revealed very low levels of confidence for each outcome of response
      to MPH. The results of clinical trials and naturalistic studies regarding the
      effect size between different polymorphisms of SLC6A3 were contradictory.
      Therefore, further research is recommended.

PMID- 29171686
TI  - Ni@Ru and NiCo@Ru Core-Shell Hexagonal Nanosandwiches with a Compositionally
      Tunable Core and a Regioselectively Grown Shell.
AB  - The development of highly active electrocatalysts is crucial for the advancement
      of renewable energy conversion devices. The design of core-shell nanoparticle
      catalysts represents a promising approach to boost catalytic activity as well as
      save the use of expensive precious metals. Here, a simple, one-step synthetic
      route is reported to prepare hexagonal nanosandwich-shaped Ni@Ru core-shell
      nanoparticles (Ni@Ru HNS), in which Ru shell layers are overgrown in a
      regioselective manner on the top and bottom, and around the center section of a
      hexagonal Ni nanoplate core. Notably, the synthesis can be extended to NiCo@Ru
      core-shell nanoparticles with tunable core compositions (Ni3 Cox @Ru HNS). Core
      shell HNS structures show superior electrocatalytic activity for the oxygen
      evolution reaction (OER) to a commercial RuO2 black catalyst, with their OER
      activity being dependent on their core compositions. The observed trend in OER
      activity is correlated to the population of Ru oxide (Ru4+ ) species, which can
      be modulated by the core compositions.

PMID- 29171687
TI  - Enhancing the Sequential Conversion-Alloying Reaction of Mixed Sn-S Hybrid Anode
      for Efficient Sodium Storage by a Carbon Healed Graphene Oxide.
AB  - To date, the possible depletion of lithium resources has become relevant, giving
      rise to the interest in Na-ion batteries (NIBs) as promising alternatives to Li
      ion batteries. While extensive investigations have examined various transition
      metal oxides and chalcogenides as anode materials for NIBs, few of these have
      been able to utilize their high specific capacity in sodium-based systems because
      of their irreversibility in a charge/discharge process. Here, the mixed Sn-S
      nanocomposites uniformly distributed on reduced graphene oxide are prepared via a
      facile hydrothermal synthesis and a unique carbothermal reduction process,
      producing ultrafine nanoparticle with the size of 2 nm. These nanocomposites are
      experimentally confirmed to overcome the intrinsic drawbacks of tin sulfides such
      as large volume change and sluggish diffusion kinetics, demonstrating an
      outstanding electrochemical performance: an excellent specific capacity of 1230
      mAh g-1 , and an impressive rate capability (445 mAh g-1 at 5000 mA g-1 ). The
      electrochemical behavior of a sequential conversion-alloying reaction for the
      anode materials is investigated, revealing both the structural transition and the
      chemical state in the discharge/charge process. Comprehension of the reaction
      mechanism for the mixed Sn-S/rGO hybrid nanocomposites makes it a promising
      electrode material and provides a new approach for the Na-ion battery anodes.

PMID- 29171688
TI  - Chemistry in Confinement: Copper and Palladium Catalyzed Ecofriendly Organic
      Transformations within Porous Frameworks.
AB  - A concise account on the use of transition metals copper (Cu) and palladium (Pd),
      as their cations as well as nanoparticles exchanged/immobilized onto porous
      frameworks such as zeolites, metal organic frameworks (MOFs), covalent organic
      polymers (COPs) and hollow nanostructures, functioning as catalysts in organic
      synthesis is presented. This biomimetic account, "focusing on catalytic systems
      in confinement" within zero-dimensional microenvironments and second sphere
      coordination covers primarily results from our group on N-sulfonylketenimine
      mediated cycloaddition, hydrogenation and C-C bond forming reactions, thus
      providing an interesting insight into the versatility and utility of these Cu and
      Pd catalysts. Other significant advantages and green credentials of confinement
      such as stability, selectivity, reusability, promotion of multicomponent
      reactions, use of green solvents, atom economy, and use of ambient conditions are
      highlighted at appropriate places. In the final section, our views on the current
      achievements and the future prospects in this area are summarized.

PMID- 29171689
TI  - The moderating role of regulatory emotional self-efficacy on smoking craving: An
      ecological momentary assessment study.
AB  - Emotion is presumed as a major reason for smoking, but this hypothesis needs
      support from data with high ecological validity. Regulatory emotional self
      efficacy (RESE) is key for emotion regulation, therefore RESE is likely to
      moderate the relationship between emotional states and smoking. The present study
      used the ecological momentary assessment (EMA) to record the levels of pleasure,
      arousal, and smoking craving in 33 male current smokers' daily lives, and
      examined the moderating effect of RESE in the prediction relationship between
      emotion and craving. The results showed that either end of the pleasure
      dimension, namely the high positive or high negative affect, predicted higher
      smoking craving. A similar pattern was also discovered in the arousal dimension,
      in which either of the activation and deactivation ends predicted higher smoking
      craving. Moreover, the prediction of negative affect on smoking craving was
      weakened by higher RESE, especially by the higher self-efficacy in managing
      negative emotions. In conclusion, smoking craving is closely related with
      immediate emotional states, and RESE reveals promising value in the reduction of
      smoking behavior. We discuss the possibility of expanding the RESE frame.

PMID- 29171690
TI  - Discovery of 2D Anisotropic Dirac Cones.
AB  - 2D anisotropic Dirac cones are observed in chi3 borophene, a monolayer boron
      sheet, using high-resolution angle-resolved photoemission spectroscopy. The Dirac
      cones are centered at the X and X' points. The data also reveal that the
      hybridization between borophene and Ag(111) is very weak, which explains the
      preservation of the Dirac cones. As chi3 borophene has been predicated to be a
      superconductor, the results may stimulate further research interest in the novel
      physics of borophene, such as the interplay between Cooper pairs and the massless
      Dirac fermions.

PMID- 29171691
TI  - Na-Cation-Assisted Exfoliation of MX2 (M = Mo, W; X = S, Se) Nanosheets in an
      Aqueous Medium with the Aid of a Polymeric Surfactant for Flexible Polymer
      Nanocomposite Memory Applications.
AB  - 2D nanosheets of transition metal dichalcogenides (TMDCs) have been attracting
      attention due to their sizable band gap. Facile and effective Na-cation-assisted
      exfoliation of TMDC (MX2 , M = Mo, W; X = S, Se) nanosheets in an aqueous medium
      and their application as a composite filler in a polyvinyl alcohol (PVA) matrix
      are explored in this work. The presence of Na cations is highly beneficial for
      exfoliating defect-free and few-layer MX2 nanosheets in water in the presence of
      small-sized micelles of polymeric surfactant, and significantly elevates the
      exfoliation yield by more than one order of magnitude compared to a conventional
      surfactant-assisted exfoliation. The strategy suggested in this work is very
      advantageous compared to both Li cation intercalation in organic solvents and
      conventional low-yield surfactant-assisted exfoliations. As an application of the
      exfoliated nanosheets, the fabrication of memory devices with the configuration
      of Ga-doped ZnO/MX2 -PVA/Ag is demonstrated, and they exhibit bistable and write
      once-read-many-times resistive switching behavior with a high ON/OFF current
      ratio of 3 * 103 at -1.0 V (for WS2 ) and 2.0 V (for MoS2 ). Furthermore, MX2 
      PVA nanocomposite fibrous films and mats are successfully fabricated using an
      electrospinning technique, which can expand the use of TMDC nanofillers in
      applications involving highly flexible polymer-based MX2 composites.

PMID- 29171693
TI  - Questions, challenges and perspectives relating to Internet gaming disorder.

PMID- 29171692
TI  - 8-Mercaptoguanine Derivatives as Inhibitors of Dihydropteroate Synthase.
AB  - Dihydropteroate synthase (DHPS) is an enzyme of the folate biosynthesis pathway,
      which catalyzes the formation of 7,8-dihydropteroate (DHPt) from 6-hydroxymethyl
      7,8-dihydropterin pyrophosphate (DHPPP) and para-aminobenzoic acid (pABA). DHPS
      is the long-standing target of the sulfonamide class of antibiotics that compete
      with pABA. In the wake of sulfa drug resistance, targeting the structurally rigid
      (and more conserved) pterin site has been proposed as an alternate strategy to
      inhibit DHPS in wild-type and sulfa drug resistant strains. Following the work on
      developing pterin-site inhibitors of the adjacent enzyme 6-hydroxymethyl-7,8
      dihydropterin pyrophosphokinase (HPPK), we now present derivatives of 8
      mercaptoguanine, a fragment that binds weakly within both enzymes, and quantify
      sub-MUm binding using surface plasmon resonance (SPR) to Escherichia coli DHPS
      (EcDHPS). Eleven ligand-bound EcDHPS crystal structures delineate the structure
      activity relationship observed providing a structural framework for the rational
      development of novel, substrate-envelope-compliant DHPS inhibitors.

PMID- 29171694
TI  - Multifunctional Diketopyrrolopyrrole-Based Conjugated Polymers with Perylene
      Bisimide Side Chains.
AB  - Two conjugated polymers based on diketopyrrolopyrrole (DPP) in the main chain
      with different content of perylene bisimide (PBI) side chains are developed. The
      influence of PBI side chain on the photovoltaic performance of these DPP-based
      conjugated polymers is systematically investigated. This study suggests that the
      PBI side chains can not only alter the absorption spectrum and energy level but
      also enhance the crystallinity of conjugated polymers. As a result, such polymers
      can act as electron donor, electron acceptor, and single-component active layer
      in organic solar cells. These findings provide a new guideline for the future
      molecular design of multifunctional conjugated polymers.

PMID- 29171695
TI  - Meeting report: The first international conference on xenotransplantation in
      Chengdu, China.

PMID- 29171696
TI  - Synthesis of Two Well-Defined Quadruple-Stranded Copolymers having Two Kinds of
      Backbones by Postpolymerization of a Helical Template Polymer.
AB  - A brand new, soluble quadruple-stranded copolymer is synthesized by using a self
      template polymer from a new monomer. In addition, another very unique quadruple
      stranded copolymer having a pi-pi stacking supramolecular polymer main chain is
      synthesized by selective photocyclic aromatization of the quadruple-stranded
      copolymer. The two quadruple-stranded copolymers gave self-standing membranes.

PMID- 29171697
TI  - RuII Photosensitizer-Functionalized Two-Dimensional MoS2 for Light-Driven
      Hydrogen Evolution.
AB  - Metallic-phase molybdenum disulfide (1T-MoS2 ) nanosheets have proven to be
      highly active in the hydrogen evolution reaction (HER). We describe construction
      of photosensitizer functionalized 1T-MoS2 by covalently tethering the molecular
      photosensitizer [RuII (bpy)3 ]2+ (bpy=2,2'-bipyridine) on 1T-MoS2 nanosheets.
      This was achieved by covalently tethering the bpy ligand to 1T-MoS2 nanosheets,
      and subsequent complexation with [RuII (bpy)2 Cl2 ] to yield [RuII (bpy)3 ]-MoS2
      . The obtained [RuII (bpy)3 ]-MoS2 nanosheets were characterized using infra-red,
      electronic absorption, X-ray photoelectron, and Raman spectroscopies, X-ray
      powder diffraction and electron microscopy. The fabricated material exhibited a
      significant improvement of photocurrent and HER performance, demonstrating the
      potential of such two-dimensional [RuII (bpy)3 ]-MoS2 constructs in
      photosensitized HER.

PMID- 29171698
TI  - Construction of Complex Co3 O4 @Co3 V2 O8 Hollow Structures from Metal-Organic
      Frameworks with Enhanced Lithium Storage Properties.
AB  - A novel metal-organic-framework-engaged strategy is demonstrated for the
      preparation of multishelled Co3 O4 @Co3 V2 O8 hybrid nanoboxes. This strategy
      relies on the unique reaction of zeolitic imidazolate framework-67 with the
      vanadium source of vanadium oxytriisopropoxide. Benefitting from the synthetic
      versatility, a series of nanostructures can be realized including triple-shelled
      and double-shelled Co3 O4 @Co3 V2 O8 nanoboxes and single-shelled Co3 V2 O8
      nanoboxes. When evaluated as electrode materials for lithium-ion batteries, these
      unique hollow structures demonstrate remarkable lithium storage properties. For
      example, the triple-shelled Co3 O4 @Co3 V2 O8 nanoboxes retain a high capacity of
      948 mAh g-1 after 100 cycles at 100 mA g-1 .

PMID- 29171699
TI  - Higher adaptive functioning and lower rate of psychotic comorbidity in married
      versus unmarried individuals with 22q11.2 deletion syndrome.
AB  - 22q11.2 deletion syndrome (22q11.2DS) is a relatively common genetic disorder.
      Due to improvement in pediatric care, affected individuals live into adulthood,
      some of whom marry or have committed relationships, and reproduce. The current
      study aimed to identify the factors that discriminate between married and
      unmarried adults with 22q11.2DS. In the presents study, 90 adults with 22q11.2DS
      (48 men/42 women), aged 29.8 +/- 10.3 years, were included in the analysis.
      Psychiatric comorbidities, IQ score, and adaptive functioning were assessed using
      gold-standard diagnostic tools. Demographic factors, marital status, and
      reproductive status were evaluated by self-reports. Of the sample 25 adults
      (27.7%) were married and 14 (56%) of those had children. Married, as compared to
      unmarried individuals, were older, had less psychotic comorbidities, showed
      higher adaptive functioning in all domains of the Vineland Adaptive Behavior
      Scale, and had higher rates of independent living and sustained employment.
      Unexpectedly, married individuals showed higher rates of mood disorders and full
      scale IQ scores did not discriminate between the groups. We propose that multiple
      factors are associated with marital status among individuals with 22q11.2DS.
      Identification of key personal, functional, and social characteristics of those
      who married and reproduced may help counseling health professionals and
      clinicians in advising affected individuals and their families.

PMID- 29171701
TI  - Electrochemical Conversion of Phthaldianilides to Phthalazin-1,4-diones by
      Dehydrogenative N-N Bond Formation.
AB  - The electrochemical synthesis of 6-membered rings via anodic dianilide N-N
      coupling is challenging due to concurring benzoxazole co-formation. The rigidity
      of the a phthalic acid backbone allows a novel access to phthalazin-1,4-diones by
      N-N bond formation using anodically generated amidyl radicals. Since conventional
      synthetic routes to phthalazin-1,4-diones require the use of toxic N,N'
      diarylhydrazines and generate reagent waste, a safer and more sustainable
      approach is required. Easy accessible starting materials, a broad scope of
      applicable functional groups, promising yields, and a very simple set-up elevate
      this sustainable method.

PMID- 29171700
TI  - Practical strategies for improving outcomes in T2DM: The potential role of
      pioglitazone and DPP4 inhibitors.
AB  - T2DM is a complex disease underlined by multiple pathogenic defects responsible
      for the development and progression of hyperglycaemia. Each of these factors can
      now be tackled in a more targeted manner thanks to glucose-lowering drugs that
      have been made available in the past 2 to 3 decades. Recognition of the
      multiplicity of the mechanisms underlying hyperglycaemia calls for treatments
      that address more than 1 of these mechanisms, with more emphasis placed on the
      earlier use of combination therapies. Although chronic hyperglycaemia contributes
      to and amplifies cardiovascular risk, several trials have failed to show a marked
      effect from intensive glycaemic control. During the past 10 years, the effect of
      specific glucose-lowering agents on cardiovascular risk has been explored with
      dedicated trials. Overall, the cardiovascular safety of the new glucose-lowering
      agents has been proven with some of the trials summarized in this review, showing
      significant reduction of cardiovascular risk. Against this background,
      pioglitazone, in addition to exerting a sustained glucose-lowering effect, also
      has ancillary metabolic actions of potential interest in addressing the
      cardiovascular risk of T2DM, such as preservation of beta-cell mass and function.
      As such, it seems a logical agent to combine with other oral anti-hyperglycaemic
      agents, including dipeptidyl peptidase-4 inhibitors (DPP4i). DPP4i, which may
      also have a potential to preserve beta-cell function, is available as a fixed
      dose combination with pioglitazone, and could, potentially, attenuate some of the
      side effects of pioglitazone, particularly if a lower dose of the
      thiazolidinedione is used. This review critically discusses the potential for
      early combination of pioglitazone and DPP4i.

PMID- 29171702
TI  - Screening for risk of violence using service users' self-perceptions: A
      prospective study from an acute mental health unit.
AB  - Service users' self-perception of risk has rarely been emphasized in violence
      risk assessments. A recent review pointed to the importance of a
      multidisciplinary approach, because different perspectives may provide a deeper
      and improved understanding of risk assessment. The aim of this study was to
      investigate service users' perceptions of their own risk of committing violence,
      using a self-report risk scale, to determine the feasibility and efficacy of this
      potential violence risk marker during acute mental health hospitalization. All
      service users admitted to a psychiatric emergency hospital in Norway during one
      calendar year were included (N = 512). Nearly 80% self-reported no risk or low
      risk; only seven (1.4%) reported moderate risk or high risk. Service users who
      reported moderate risk, high risk, don't know, or won't answer were more likely
      to be violent (OR = 4.65, 95% CI = 2.79-7.74) compared with those who reported no
      risk or low risk. There was a significant gender interaction with higher OR for
      women on both univariate and multivariate analyses. Although the OR was higher
      for women, women's violence rate (11.0%) was almost half that of men (21.8%). For
      women, sensitivity and specificity were 0.55 and 0.88, respectively;
      corresponding values for men were 0.40 and 0.80. Inclusion of self-perception of
      violence risk is the first step towards service users' collaborative involvement
      in violence prediction; these results indicate that self-perception can
      contribute to violence risk assessments in acute mental health settings. Findings
      also indicate that there are gender differences in these assessments.

PMID- 29171703
TI  - Homo- and Copolycyclotrimerization of Aromatic Internal Diynes Catalyzed with Co2
      (CO)8 : A Facile Route to Microporous Photoluminescent Polyphenylenes with
      Hyperbranched or Crosslinked Architecture.
AB  - This study reports the first Co2 (CO)8 -catalyzed [2+2+2] polycyclotrimerization
      by the transformation of internal ethynyl groups of aromatic diyne monomers. The
      reaction yields polycyclotrimers of polyphenylene-type with either hyperbranched
      or partly crosslinked architecture. The homopolycyclotrimerization of the
      monomers with two ethynyl groups per one molecule, namely 1,4
      bis(phenylethynyl)benzene, 4,4'-bis(phenylethynyl)biphenyl, and 4
      (phenylethynyl)phenylacetylene, gives partly crosslinked, insoluble
      polyphenylenes. The soluble, hyperbranched polyphenylenes are generated via
      copolycyclotrimerization of 1,4-bis(phenylethynyl)benzene with 1,2
      diphenylacetylene (average number of ethynyl groups per monomer molecule < 2).
      This one-step polycyclotrimerization path to hyperbranched or partly crosslinked
      polyphenylenes is an alternative to the synthesis of these polymers by Diels
      Alder transformation of substituted cyclopentadienones. All polyphenylenes
      prepared exhibit photoluminescence with emission maxima ranging from 381 to 495
      nm. Polyphenylenes with a less compact packing of segments are microporous
      (specific surface area up to 159 m2 g-1 ), which is particularly important in the
      case of soluble polyphenylenes because they can be potentially used to prepare
      microporous layers.

PMID- 29171704
TI  - A qualitative investigation of physical activity compensation among older adults.
AB  - OBJECTIVES: This study explored the mechanisms of physical activity (PA)
      compensation among older adults who recently reduced their non-exercise physical
      activity (NEPA) in response to a structured PA intervention. DESIGN: A post
      trial, retrospective qualitative process evaluation using interviews was
      employed. METHODS: Levels of PA compensation were determined by comparing NEPA
      prior to and during the final week of a 4-week structured PA intervention. Those
      who reduced their NEPA by 10% or greater were considered as compensators.
      Interviews were conducted with older adult compensators (mean age = 58.56 +/-
      3.88 years; n = 9), employing thematic analysis to identify potential mechanisms
      of PA compensation. RESULTS: The findings suggest that the majority of
      participants were unaware that they had compensated in their PA, suggesting that
      this may be a non-volitional process. Most participants perceived PA compensation
      to hold negative implications for health and well-being. Physiological processes
      of fatigue and delayed onset of muscle soreness were cited as the principal cause
      of PA compensation, whereas psychological processes including a drive to be
      inactive, fear of overexertion, deficient motivation, and perceived time
      constraints were cited to a lesser extent. CONCLUSION: A range of physiological
      and psychological compensatory barriers were identified. Implications of and
      methods to overcome these compensatory barriers are discussed. Statement of
      contribution What is already known on this subject? Physical activity
      compensation holds negative implications for physical activity promotion and
      health. Older adults are an age group more likely to compensate in their physical
      activity levels. What does this study add? Physical activity compensation may be
      a result of a range of physiological and psychological processes including
      fatigue and delayed onset of muscle soreness, compensatory health beliefs, fear
      of overexertion, deficient motivation, and perceived time constraints. Most older
      adult compensators may be unaware they are compensating and, however, agree that
      physical activity compensation has negative implications for health and well
      being.

PMID- 29171705
TI  - Broadening the Photoresponse to Near-Infrared Region by Cooperating Fullerene and
      Nonfullerene Acceptors for High Performance Ternary Polymer Solar Cells.
AB  - Ternary polymer solar cells (PSCs) based on multiple materials with level
      matching and complementary absorptions are regarded as an efficient way to
      overcome the light-harvesting restriction to surpass high-performance binary
      PSCs. This study introduces the third component, nonfullerene acceptor IEICO,
      into binary PSC-based PBDTBDD:PC71 BM to fabricate ternary PSC with one donor and
      two acceptors. By carefully tuning the third component ratio and cathode
      engineering, the resulting ternary PSC shows a power conversion efficiency of
      10.51%, greatly improved in comparison with binary PSCs-based PBDTBDD:PC71 BM
      (7.86%) and PBDTBDD:IEICO (5.19%). In addition to extended light absorption, the
      third component IEICO could accelerate charge-carrier transfer, decrease charge
      recombination, and increase electron collection, resulting from cascade energy
      levels, and ameliorate the device morphology to increase the contact area of the
      active layer and cathode buffer layer. This work demonstrates that ternary PSC
      incorporated with IEICO is a promising structure for producing high performance
      PSCs.

PMID- 29171706
TI  - Controllable Surface Reorganization Engineering on Cobalt Phosphide Nanowire
      Arrays for Efficient Alkaline Hydrogen Evolution Reaction.
AB  - Developing highly efficient hydrogen evolution reaction (HER) catalysts in
      alkaline media is considered significant and valuable for water splitting.
      Herein, it is demonstrated that surface reorganization engineering by oxygen
      plasma engraving on electocatalysts successfully realizes a dramatically enhanced
      alkaline HER activity. Taking CoP nanowire arrays grown on carbon cloth (denoted
      as CoP NWs/CC) as an example, the oxygen plasma engraving can trigger moderate
      CoOx species formation on the surface of the CoP NWs/CC, which is visually
      verified by the X-ray absorption fine structure, high-resolution transmission
      electron microscopy, and energy-dispersive spectrometer (EDS) mapping. Benefiting
      from the moderate CoOx species formed on the surface, which can promote the water
      dissociation in alkaline HER, the surface reorganization of the CoP NWs/CC
      realizes almost fourfold enhanced alkaline HER activity and a 180 mV decreased
      overpotential at 100 mA cm-2 , compared with the pristine ones. More
      interestingly, this surface reorganization strategy by oxygen plasma engraving
      can also be effective to other electrocatalysts such as free-standing CoP, Co4 N,
      O-CoSe2 , and C-CoSe2 nanowires, which verifies the universality of the strategy.
      This work thus opens up new avenues for designing alkaline HER electrocatalysts
      based on oxygen plasma engraving.

PMID- 29171707
TI  - Basic Remarks on Acidity.
AB  - This Review provides a unified view on Bronsted acidity. For this purpose, a
      brief overview of the concepts acidity, acid strengths, and pH value is given,
      including problems, proposed solutions, and the use of the pHabs /pHabsH2O scale
      as a unifying concept. Thereafter, some examples of the accessibility and
      application of unified pHabs values are given. The Review is rounded off with the
      analogy of acid-base chemistry to redox chemistry with the introduction of the
      unified redox scale peabs . The combination of pHabs and peabs values in the
      protoelectric potential map (PPM), as elaborated in ongoing studies on the
      thermochemistry of single ions, provides a means to classify and to compare all
      possible acid-base/redox reactions in a medium-independent and, thus, unified
      fashion.

PMID- 29171708
TI  - Functional Carbon Quantum Dots: A Versatile Platform for Chemosensing and
      Biosensing.
AB  - Carbon quantum dot has emerged as a new promising fluorescent nanomaterial due to
      its excellent optical properties, outstanding biocompatibility and accessible
      fabrication methods, and has shown huge application perspective in a variety of
      areas, especially in chemosensing and biosensing applications. In this personal
      account, we give a brief overview of carbon quantum dots from its origin and
      preparation methods, present some advance on fluorescence origin of carbon
      quantum dots, and focus on development of chemosensors and biosensors based on
      functional carbon quantum dots. Comprehensive advances on functional carbon
      quantum dots as a versatile platform for sensing from our group are included and
      summarized as well as some typical examples from the other groups. The biosensing
      applications of functional carbon quantum dots are highlighted from selective
      assays of enzyme activity to fluorescent identification of cancer cells and
      bacteria.

PMID- 29171709
TI  - The influence of inflammation and hematocrit on clot strength in canine
      thromboelastographic hypercoagulability.
AB  - OBJECTIVE: To investigate parameters causing canine thromboelastographic
      hypercoagulability and to investigate whether thromboelastography (TEG) with
      Cytochalasin D (Cyt D) added is related to parameters of platelet activity.
      DESIGN: Prospective observational study on hemostatic and inflammatory
      parameters. Data were collected between November 2012 and July 2013. SETTING:
      University teaching hospital. ANIMALS: Twenty-eight dogs suffering from diseases
      predisposing to thrombosis and 19 clinically healthy dogs. Diseased dogs were
      enrolled if they fulfilled inclusion criteria regarding age, size, informed
      client consent, and obtained a diagnosis of a disease that has been associated
      with thrombosis or hypercoagulability. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Parameters of coagulation and anticoagulation, fibrinolysis, and
      antifibrinolysis, platelet activity, inflammation, platelet count, and hematocrit
      were measured using CBC, TEG, platelet aggregation on multiplate, platelet
      activity on flow cytometry, and hemostatic and inflammatory markers on plasma and
      serum analyses. ANOVA and multilinear regression analyses indicated that
      especially hematocrit and the inflammatory parameters C-reactive protein and
      interleukin-8 showed best association with overall clot strength in diseased dogs
      with hypercoagulable TEG tracings. Ratios presumed to reflect platelet
      contribution to the TEG tracing obtained in TEG analyses with Cyt D were related
      especially with hematocrit and P-selectin expression of platelets measured after
      gamma-Thrombin activation on flow cytometry. CONCLUSION: Overall clot strength in
      TEG analyses of the hypercoagulable dogs included in the present study appears to
      be primarily associated with inflammation as well as hematocrit. Furthermore, the
      ratio between standard TEG analyses and TEG analyses with Cyt D may reflect some
      degree of platelet activity.

PMID- 29171710
TI  - Asymmetrically Encapsulated Vertical ITO/MoS2 /Cu2 O Photodetector with Ultrahigh
      Sensitivity.
AB  - Strong light absorption, coupled with moderate carrier transport properties,
      makes 2D layered transition metal dichalcogenide semiconductors promising
      candidates for low intensity photodetection applications. However, the
      performance of these devices is severely bottlenecked by slow response with
      persistent photocurrent due to long lived charge trapping, and nonreliable
      characteristics due to undesirable ambience and substrate effects. Here ultrahigh
      specific detectivity (D*) of 3.2 * 1014 Jones and responsivity (R) of 5.77 * 104
      A W-1 are demonstrated at an optical power density (Pop ) of 0.26 W m-2 and
      external bias (Vext ) of -0.5 V in an indium tin oxide/MoS2 /copper oxide/Au
      vertical multi-heterojunction photodetector exhibiting small carrier transit
      time. The active MoS2 layer being encapsulated by carrier collection layers
      allows us to achieve repeatable characteristics over large number of cycles with
      negligible trap assisted persistent photocurrent. A large D* > 1014 Jones at zero
      external bias is also achieved due to the built-in field of the asymmetric
      photodetector. Benchmarking the performance against existing reports in
      literature shows a viable pathway for achieving reliable and highly sensitive
      photodetectors for ultralow intensity photodetection applications.

PMID- 29171713
TI  - Black Phosphorus Quantum Dots with Renal Clearance Property for Efficient
      Photodynamic Therapy.
AB  - Black phosphorus (BP) nanomaterials have emerged as rapidly rising stars in the
      field of nanomedicine. In this work, BP quantum dots (BPQDs) are synthesized and
      their potential as photosensitizers is investigated for the first time. The BPQDs
      present good stability in physiological medium and no appreciable cytotoxicity.
      More importantly, the BPQDs can be rapidly eliminated from the body in their
      intact form via renal clearance due to their ultrasmall hydrodynamic diameter
      (5.4 nm). Both in vitro and in vivo studies indicate that the BPQDs have
      excellent photodynamic effect under light irradiation that can effectively
      generate reactive oxygen species to kill cancer cells. The BPQDs thus can serve
      as biocompatible and powerful photosensitizers for efficient photodynamic
      therapy.

PMID- 29171712
TI  - Perspectives in allergen immunotherapy: 2017 and beyond.
AB  - The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides
      a regular platform for global experts from academia, allergy clinics, regulatory
      authorities and industry to review developments in the field of allergen
      immunotherapy (AIT). The most recent meeting, held in February 2017, had two main
      themes: advances in AIT and hot topics in AIT from the regulatory point of view.
      The first theme covered opportunities for personalized AIT, advances in adjuvants
      and delivery systems, and the development of new molecules and future vaccines
      for AIT. Key topics in the second part of the meeting were the effects of the
      enactment of European Directive 2001/83 on the availability of allergens for
      therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies
      in the field, the future role of allergen exposure chambers in AIT studies and
      specific considerations in performing AIT studies in the paediatric population.
      Finally, the group highlighted the forthcoming EAACI guidelines and their
      particular importance for the standardization of practice in the treatment of
      allergies. This review presents a comprehensive insight into those panel
      discussions and highlights unmet needs and also possible solutions to them for
      the future.

PMID- 29171714
TI  - Biomimetic Materials and Fabrication Approaches for Bone Tissue Engineering.
AB  - Various strategies have been explored to overcome critically sized bone defects
      via bone tissue engineering approaches that incorporate biomimetic scaffolds.
      Biomimetic scaffolds may provide a novel platform for phenotypically stable
      tissue formation and stem cell differentiation. In recent years, osteoinductive
      and inorganic biomimetic scaffold materials have been optimized to offer an osteo
      friendly microenvironment for the osteogenic commitment of stem cells.
      Furthermore, scaffold structures with a microarchitecture design similar to
      native bone tissue are necessary for successful bone tissue regeneration. For
      this reason, various methods for fabricating 3D porous structures have been
      developed. Innovative techniques, such as 3D printing methods, are currently
      being utilized for optimal host stem cell infiltration, vascularization, nutrient
      transfer, and stem cell differentiation. In this progress report, biomimetic
      materials and fabrication approaches that are currently being utilized for
      biomimetic scaffold design are reviewed.

PMID- 29171715
TI  - Restenosis patterns after bioresorbable vascular scaffold implantation:
      Angiographic substudy of the GHOST-EU registry.
AB  - OBJECTIVES: To evaluate pattern of in-BVS-restenosis after bioresorbable vascular
      scaffold (BVS) implantation. BACKGROUND: In-stent restenosis morphology impacts
      target lesion revascularization (TLR) rates and clinical outcomes. Although
      several trials report on outcomes after BVS implantation, information about in
      BVS restenosis pattern is still lacking. METHODS: Between November 2011 and
      January 2014, in 7 of 10 European centers participating in the GHOST-EU registry,
      668 patients underwent BVS implantation. Of them 164 patients (200 lesions)
      underwent an additional angiogram 3 to 12 months after index PCI. RESULTS: Binary
      in-BVS restenosis (IBR) (in-segment diameter stenosis >=50%) was observed in
      12.7% (21 of 164) of patients (30 lesions), with a TLR rate of 16.5%. The IBR
      morphology was classified as focal margin in 50.0%, focal body in 26.7%,
      multifocal in 10.0%, and diffuse in 13.3% of these cases. Treatment of small
      vessels (OR 5.49, 95% CI 1.6-18.8, P < 0.01) was identified as independent
      predictor of IBR. Performing predilatation (OR 0.13, 95% CI 0.02-1.04, P = 0.06),
      high-pressure postdilatation (OR 3.16, 95% CI 0.90-11.18, P = 0.07) as well as
      treatment of acute coronary syndrome (OR 0.18, 95% CI 0.03-1.12, P = 0.07) seem
      to strongly influence this risk. CONCLUSIONS: The IBR morphology is mostly focal
      involving particularly the BVS margins suggesting association with procedural
      aspects in this early experience with BVS. Treatment of small vessels is the
      strongest predictor of higher IBR risk.

PMID- 29171716
TI  - Architecting Graphene Oxide Rolled-Up Micromotors: A Simple Paper-Based
      Manufacturing Technology.
AB  - A graphene oxide rolled-up tube production process is reported using wax-printed
      membranes for the fabrication of on-demand engineered micromotors at different
      levels of oxidation, thickness, and lateral dimensions. The resultant graphene
      oxide rolled-up tubes can show magnetic and catalytic movement within the
      addition of magnetic nanoparticles or sputtered platinum in the surface of
      graphene-oxide-modified wax-printed membranes prior to the scrolling process. As
      a proof of concept, the as-prepared catalytic graphene oxide rolled-up
      micromotors are successfully exploited for oil removal from water. This
      micromotor production technology relies on an easy, operator-friendly, fast, and
      cost-efficient wax-printed paper-based method and may offer a myriad of hybrid
      devices and applications.

PMID- 29171717
TI  - Sex-related relationships between uric acid and target organ damage in
      hypertension.
AB  - Heterogeneous results have been obtained in the relationship between serum uric
      acid (SUA) and target organ damage (TOD) in patients with hypertension. Clinic
      blood pressure, SUA, and cardiac, arterial (carotid and aortic), and renal TOD
      were assessed in 762 consecutive patients with hypertension. Hyperuricemia was
      defined as an SUA >7.0 in men and >6.0 mg/dL in women. Men with hyperuricemia
      compared with those with normal SUA showed lower estimated glomerular filtration
      rates and E/A ratios and a higher prevalence of carotid plaques. Women with
      hyperuricemia showed lower estimated glomerular filtration rates and E/A ratios
      and a higher intima-media thickness. Except for pulse wave velocity, all TODs
      significantly correlated with SUA. However, at multivariate analysis, only
      estimated glomerular filtration rate was significantly determined by SUA. Our
      data provide evidence on the role of SUA in the development of TOD only in the
      case of renal alteration. It is likely that SUA may indirectly act on the other
      TODs through the increase in blood pressure and the decrease in glomerular
      filtration rate.

PMID- 29171718
TI  - Revealing the Fate of Transplanted Stem Cells In Vivo with a Novel Optical
      Imaging Strategy.
AB  - Stem-cell-based regenerative medicine holds great promise in clinical practices.
      However, the fate of stem cells after transplantation, including the
      distribution, viability, and the cell clearance, is not fully understood, which
      is critical to understand the process and the underlying mechanism of
      regeneration for better therapeutic effects. Herein, we develop a dual-labeling
      strategy to in situ visualize the fate of transplanted stem cells in vivo by
      combining the exogenous near-infrared fluorescence imaging in the second window
      (NIR-II) and endogenous red bioluminescence imaging (BLI). The NIR-II
      fluorescence of Ag2 S quantum dots is employed to dynamically monitor the
      trafficking and distribution of all transplanted stem cells in vivo due to its
      deep tissue penetration and high spatiotemporal resolution, while BLI of red
      emitting firefly luciferase (RfLuc) identifies the living stem cells after
      transplantation in vivo because only the living stem cells express RfLuc. This
      facile strategy allows for in situ visualization of the dynamic trafficking of
      stem cells in vivo and the quantitative evaluation of cell translocation and
      viability with high temporal and spatial resolution, and thus reports the fate of
      transplanted stem cells and how the living stem cells help, regeneration, for an
      instance, of a mouse with acute liver failure.

PMID- 29171719
TI  - Developing an adherence in hypertension questionnaire short version: MUAH-16.
AB  - The Maastricht Utrecht Adherence in Hypertension (MUAH) questionnaire provides
      clinicians with information about the causes of a patient's poor adherence to
      antihypertensive drugs. In this study, the authors aimed to develop and validate
      a short version of the MUAH questionnaire. After an exploratory factor analysis,
      the number of MUAH items was reduced. The original MUAH questionnaire (model 1)
      was compared with the 16-item MUAH short version (model 2). Next, this short
      version of MUAH (MUAH-16) with all factors correlated (model 2a) was compared
      with the short version of MUAH with four subscales that contribute to a global
      factor of adherence (model 2b). Model 1 had a poor fit to the data (chi2 269 =
      663.41, P < .001, comparative fit index = 0.695, root mean square error of
      approximation = 0.06), and model 2 had a very good fit to the data (chi2 100 =
      171.07, P < .001, comparative fit index = 0.92, root mean square error of
      approximation = 0.04). When comparing model 2a with model 2b, the chi-square
      difference of the model (Deltachi2 2 = 4.06; P = .067) revealed that the fits of
      both models were not significantly different. These findings suggest that MUAH-16
      better represents a patient's adherence to antihypertensive medication than the
      original MUAH questionnaire.

PMID- 29171720
TI  - Building resilience in regional youth: Impacts of a universal mental health
      promotion programme.
AB  - Mental health is a leading health issue facing young people today, particularly
      those living in rural and regional areas. Although public policy supports schools
      based health promotion, there is limited evidence of the efficacy of such
      programmes and the elements that enhance successful implementation in rural and
      regional areas. A study was designed to evaluate a mental health promotion
      programme, delivered collaboratively by nurses, guidance officers, and teachers,
      to 850 young people from 23 rural and regional high schools in Queensland,
      Australia. The study aims were to determine what effect the intervention had on
      young peoples' resilience, coping, and self-efficacy, and to understand the
      implications of delivering the programme in the regional Queensland school
      setting. Students completed self-report measures of self-efficacy, resilience,
      and coping strategies pre- and postprogramme, as well as at 8-week follow-up. We
      found that after programme completion there was a significant increase in self
      efficacy and in the number of positive coping strategies used by the
      participating young people. Qualitative data indicated that participants
      benefited from the collaboration between health and education sectors; that is,
      nurses, guidance officers, and teachers delivered the programme together in ways
      that were perceived to be respectful of young people and effectively discussion
      based, and engaging.

PMID- 29171721
TI  - Heparan sulfate inhibits inflammation and improves wound healing by
      downregulating the NLR family pyrin domain containing 3 (NLRP3) inflammasome in
      diabetic rats.
AB  - BACKGROUND: Heparan sulfate (HS) attenuates the inflammatory response and
      improves diabetic wound healing in rats. However, the specific mechanisms by
      which HS suppresses inflammation are not clear. Given that NLR family pyrin
      domain containing 3 (NLRP3) is a major receptor involved in innate immune
      regulation, the aim of the present study was to elucidate the effects of HS on
      NLRP3 and proinflammatory cytokines in diabetic wounds. METHODS: Full-thickness
      wounds were created on the back of diabetic rats. The experimental group received
      HS treatment (1 mg/kg, i.m., on Days 0 and 7), whereas the control group received
      vehicle (0.1% dimethylsulfoxide in 0.9% NaCl). Expression of NLRP3 and its
      downstream effector molecules, namely cleaved interleukin (IL)-1beta, IL-18,
      tumor necrosis factor (TNF)-alpha, apoptosis-associated speck-like protein
      containing a caspase recruitment domain (ASC), proteinase inhibitor 9, and
      caspase-12, in the wound tissues was examined. RESULTS: Treatment with HS
      accelerated wound healing in diabetic rats. Rats treated with HS exhibited
      decreased activation of cleaved IL-1beta, IL-18, and TNF-alpha, as well as
      decreased expression of NLRP3 and ASC. In addition, HS increased levels of
      proteinase inhibitor 9 and caspase-12. CONCLUSIONS: Heparan sulfate inhibits
      inflammation and improves wound healing by downregulating the NLRP3 inflammasome
      and cleaved IL-1beta during the wound healing process in diabetic rats.

PMID- 29171722
TI  - Magnetically Responsive Elastomer-Silicon Hybrid Surfaces for Fluid and Light
      Manipulation.
AB  - Stimuli-responsive surfaces with tunable fluidic and optical properties utilizing
      switchable surface topography are of significant interest for both scientific and
      engineering research. This work presents a surface involving silicon scales on a
      magnetically responsive elastomer micropillar array, which enables fluid and
      light manipulation. To integrate microfabricated silicon scales with
      ferromagnetic elastomer micropillars, transfer printing-based deterministic
      assembly is adopted. The functional properties of the surface are completely
      dictated by the scales with optimized lithographic patterns while the micropillar
      array is magnetically actuated with large-range, instantaneous, and reversible
      deformation. Multiple functions, such as tunable wetting, droplet manipulation,
      tunable optical transmission, and structural coloration, are designed,
      characterized, and analyzed by incorporating a wide range of scales (e.g., bare
      silicon, black silicon, photonic crystal scales) in both in-plane and out-of
      plane configurations.

PMID- 29171723
TI  - A Sterically Constrained Tricyclic PC3 Phosphine: Coordination Behavior and
      Insertion of Chalcogen Atoms into P-C Bonds.
AB  - A tricyclic phosphine has been generated that has a rigid molecular backbone with
      the P atoms exclusively bound to C(sp2 ) atoms as well as a very large Tolman
      angle and buried volume. It is an interesting new ligand in coordination
      chemistry (Au, Pd complexes) and shows unusual insertion reactions into its
      endocyclic P-C bonds facilitated by its inherent molecular strain.

PMID- 29171724
TI  - Capacitance-Assisted Sustainable Electrochemical Carbon Dioxide Mineralisation.
AB  - An electrochemical cell comprising a novel dual-component graphite and Earth
      crust abundant metal anode, a hydrogen producing cathode and an aqueous sodium
      chloride electrolyte was constructed and used for carbon dioxide mineralisation.
      Under an atmosphere of 5 % carbon dioxide in nitrogen, the cell exhibited both
      capacitive and oxidative electrochemistry at the anode. The graphite acted as a
      supercapacitive reagent concentrator, pumping carbon dioxide into aqueous
      solution as hydrogen carbonate. Simultaneous oxidation of the anodic metal
      generated cations, which reacted with the hydrogen carbonate to give mineralised
      carbon dioxide. Whilst conventional electrochemical carbon dioxide reduction
      requires hydrogen, this cell generates hydrogen at the cathode. Carbon capture
      can be achieved in a highly sustainable manner using scrap metal within the
      anode, seawater as the electrolyte, an industrially relevant gas stream and a
      solar panel as an effective zero-carbon energy source.

PMID- 29171725
TI  - Paravascular abnormalities observed by spectral domain optical coherence
      tomography are risk factors for retinoschisis in eyes with high myopia.
AB  - PURPOSE: To investigate the retinal features and distribution of paravascular
      abnormalities (PVAs) and their relationship with retinoschisis in eyes with high
      myopia. METHODS: One hundred and fifty-two eyes of 88 patients with high myopia
      [refractive error greater than -6 dioptres (D) or axial length (AL) >=26.5 mm]
      who had undergone comprehensive ophthalmic examinations were evaluated in this
      cross-sectional study. Multiple optical coherence tomography (OCT) scans were
      performed to study the microstructural alterations adjacent to the retinal
      vascular arcades and the entire macular area. The presence and distribution
      patterns of various PVAs, retinoschisis and the association between these
      parameters were analysed. RESULTS: Of the 152 highly myopic eyes, PVAs were
      detected by OCT in 126 eyes (82.9%), including paravascular microfolds in all 126
      eyes, paravascular cysts in 109 eyes (71.7%) and paravascular lamellar holes in
      44 eyes (28.9%). All three types of PVAs were observed more frequently along the
      temporal vascular arcades than along the nasal vascular arcades (p < 0.005).
      Seventy-eight eyes (51.3%) were identified with retinoschisis at retinal vascular
      arcades, most frequently in the inner plexiform layer (IPL) and along temporal
      arcades. Eyes with all three types of PVAs (microfolds, cysts and lamellar holes)
      had the highest incidence of retinoschisis at vascular arcades (p < 0.001).
      Multivariate analysis indicated that age, the AL, presence of paravascular
      microfolds and cysts, and simultaneously existence of all three types of PVAs
      were associated with an increased risk for retinoschisis at vascular arcades.
      Macular retinoschisis was detected in 25 eyes (19.8%) and presented with
      splitting of the outer retina in all cases. All seven eyes with entire macular
      area retinoschisis (S4 grade) were accompanied by retinoschisis at vascular
      arcades within multiple layers, including outer retinoschisis, IPL schisis and
      inner limiting membrane (ILM) detachment. CONCLUSION: Our findings indicated that
      all three types of PVAs and different types of retinoschisis were most frequently
      observed along the temporal vascular arcades. Eyes with paravascular microfolds
      and cysts, and those with all three paravascular lesions may in risk of
      developing retinoschisis at vascular arcades.

PMID- 29171726
TI  - Factors associated with deep circulation in the peripapillary chorioretinal
      atrophy zone in normal-tension glaucoma with myopic disc.
AB  - PURPOSE: To investigate factors associated with choroidal microcirculation in the
      peripapillary chorioretinal atrophy (PPA) zone in eyes with normal-tension
      glaucoma (NTG) and myopic disc. METHODS: In 100 eyes of 100 NTG patients with
      myopic disc and 20 eyes of 20 age-matched myopic controls, 4.5 * 4.5 mm scans
      were made of the optic nerve head with optical coherence tomography angiography
      (OCTA). Peripapillary chorioretinal atrophy (PPA) area and PPA superficial
      choroidal image intensity (PPA-CI) were calculated with image j software.
      Clinical characteristics, laser speckle flowgraphy-measured mean blur rate in the
      temporal tissue area (temporal MT), the central thresholds (the averaged standard
      automated perimetry-measured visual field thresholds in the four paracentral
      points) and 3D-OCT-measured ganglion cell complex thickness in the papillomacular
      bundle (PMB-GCCT) were recorded. RESULTS: The NTG patients had significantly
      lower intraocular pressure, PMB-GCCT and central threshold values, and a larger
      PPA area, than the controls. The area under the receiver operating
      characteristics curve to differentiate NTG with parafoveal scotoma (PFS) from
      controls was 0.76 for temporal MT, 0.85 for PPA-CI and 0.87 for PMB-GCCT.
      Univariate and multivariate analyses revealed that PPA-CI was negatively
      correlated with age, pulse rate, best-corrected visual acuity, axial length and
      PPA area, and positively correlated with temporal MT, PMB-GCCT and the central
      thresholds. CONCLUSION: Peripapillary chorioretinal atrophy (PPA)-CI was
      associated with temporal MT, ageing, bradycardia, axial length elongation and
      changes in central retinal structure and visual function in patients with NTG and
      myopic disc. Thus, microcirculation deep within the PPA zone might be a
      clinically useful biomarker of PFS in NTG.

PMID- 29171727
TI  - Wavelength Division Multiplexer Based on Semiconductor Heterostructures
      Constructed via Nanoarchitectonics.
AB  - Obtaining a wavelength division multiplexer (WDM) at the micro/nanometer level is
      a considerable challenge that holds great potential in optical communication
      technology owing to the enlarged data-carrying capacity without laying more
      fibers. Of the progress that has been made in recent years, one of the most
      promising methods is to fabricate nanoscale pattern on silicon substrate, forcing
      signals of different wavelength to enter predesigned channels due to the
      alternant changes in refractive index. However, it is not an easy task to
      incorporate light sources into these WDM systems, because of the nonradiative
      characteristics of silicon itself. This study demonstrates a successful
      integration of laser signal sources and WDM fully with 1D semiconductor
      structures. Nanowires from II-VI semiconductor serve as both lasing media and low
      loss waveguides for signal loading and delivering, respectively. On the basis of
      the distinct size-dependent cut-off effect, finely tuning the diameters of
      homojunctions would result in a controllable filtering of confined signal that
      light, beyond cut-off wavelength, cannot transfer within the narrowed segments
      any longer. These results pave the way for semiconductor photonic components
      toward integration.

PMID- 29171728
TI  - Sanger sequencing.
AB  - This poster beautifully illustrates the process and importance of Sanger
      sequencing. Developed by Diego Estrada-Rivadeneyra, it won one of the three 50th
      anniversary science communication competition prizes.

PMID- 29171729
TI  - Long-term outcomes in unilateral vocal fold paralysis patients.
AB  - OBJECTIVES/HYPOTHESIS: At presentation, unilateral vocal fold paralysis (UVFP)
      patients have different treatment options, including conservative management
      (CM), injection laryngoplasty (IL) with a temporary agent, or permanent
      medialization (PM). This study evaluates long-term outcomes for UVFP patients
      relative to intervention. STUDY DESIGN: Retrospective chart review. METHODS: A
      retrospective chart review was performed of UVFP patients who presented to the
      University of California San Francisco Voice and Swallowing Center.
      Videolaryngostroboscopy examinations were reviewed. Maximum glottic closure was
      quantified with the normalized glottic gap area (NGGA). Perceptual voice analysis
      was performed using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE
      V) at corresponding time points. RESULTS: Fifty-three patients met inclusion
      criteria. Six underwent CM only, 20 went on to require PM, 19 underwent IL only,
      and eight underwent IL and subsequent PM. NGGA at presentation was similar among
      groups; however, the CM group was noted to have more favorable CAPE-V scores for
      Breathiness (P = .007) and Loudness (P = .018). All groups had similar NGGA and
      CAPE-V scores at last follow-up. When compared to pooled data for patients who
      underwent PM, the IL group was noted to have similar NGGA and CAPE-V scores at
      presentation. Although improvements in both groups were noted following
      intervention, both groups appeared similar at last follow-up with the exception
      of Roughness, for which the IL group retained a slightly improved outcome (13.3
      vs. 18.3, P = .03). CONCLUSIONS: At presentation, UVFP patients have similar
      NGGA. This finding suggests that treatment recommendations cannot be made on the
      size of the glottic gap alone. Furthermore, in many patients, IL results in long
      term benefit with glottic closure and CAPE-V scores equivalent to that obtained
      with PM. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:430-436, 2018.

PMID- 29171730
TI  - The JUPITER registry: One-year outcomes of transapical aortic valve implantation
      using a second generation transcatheter heart valve for aortic regurgitation.
AB  - OBJECTIVES: We present 1-year outcomes of the post-market registry of a next
      generation transcatheter heart valve used for aortic regurgitation (AR).
      BACKGROUND: Transcatheter aortic valve replacement (TAVR) is routine in high-risk
      patients with aortic stenosis but is not recommended for AR. The JenaValveTM
      (JenaValve Technology GmbH, Munich, Germany) overcomes technical challenges in AR
      patients through a leaflet clipping mechanism. METHODS: The JenaValve EvalUation
      of Long Term Performance and Safety In PaTients with SEvere Aortic Stenosis oR
      Aortic Insufficiency (JUPITER) Registry is a European study to evaluate safety
      and effectiveness of this THV. From 2012-2015, 30 patients with AR were enrolled.
      RESULTS: Mean age was 74.4 +/- 9.3 years. Procedural success was 96.7% (29/30).
      One patient was converted to open surgery. No annular rupture or coronary ostia
      obstruction occurred. Mortality at 30 days was 10.0% (3/30). Combined safety
      endpoint was met in 13.3% (4/30). Paravalvular regurgitation was not
      present/trivial in 84.6% (22/26) and mild in 15.4% (4/26). Rate of permanent
      pacemaker implantation was 3.8% (1/26). One-year Kaplan-Meier survival was 79.9%,
      one-year combined efficacy was 73.1% (19/30). No further strokes were observed
      during 1 year of follow-up. CONCLUSIONS: The JenaValve overcomes technical
      challenges of TAVR in AR through a clipping mechanism. We report satisfactory
      outcomes of a multicenter registry using the JenaValve for predominant AR, as
      rate of THV embolization, residual AR and permanent pacemaker implantation was
      low. One-year results using the JenaValve for AR encourage its use for this
      indication.

PMID- 29171731
TI  - Expressions of Mast Cell Tryptase and Brain Natriuretic Peptide in Myocardium of
      Sudden Death due to Hypersensitivity and Coronary Atherosclerotic Heart Disease.
AB  - OBJECTIVES: To explore the value of mast cell tryptase and brain natriuretic
      peptide(BNP) in the differential diagnostic of sudden death due to
      hypersensitivity and coronary atherosclerotic heart disease. METHODS: Totally 30
      myocardial samples were collected from the autopsy cases in the Department of
      Forensic Pathology, Shanxi Medical University during 2010-2015. All samples were
      divided into three groups: death of craniocerebral injury group, sudden death of
      hypersensitivity group and sudden death of coronary atherosclerotic heart disease
      group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were
      detected by immunofluorescence staining and Western Blotting. RESULTS:
      Immunofluorescence staining showed that the positive staining mast cell tryptase
      appeared in myocardium of sudden death of hypersensitivity group and coronary
      atherosclerotic heart disease group. Among the three groups, the expression of
      mast cell tryptase showed significantly differences through pairwise comparison
      (P<0.05); The expression level of BNP in sudden death of coronary atherosclerotic
      heart disease group were significantly higher than the sudden death of
      hypersensitivity group and death of craniocerebral injury group (P<0.05). The
      difference of the expression level of BNP between the sudden death of
      hypersensitivity group and the death of craniocerebral injury group had no
      statistical significance (P>0.05). CONCLUSIONS: The combined detection of the
      mast cell tryptase and BNP in myocardium is expected to provide help for the
      forensic differential diagnosis of sudden death due to hypersensitivity and
      coronary atherosclerotic heart disease.

PMID- 29171732
TI  - Correlation between RNA Degradation Patterns of Rat's Brain and Early PMI at
      Different Temperatures.
AB  - OBJECTIVES: To explore the correlation between early postmortem interval (PMI)
      and eight RNA markers of rat's brain at different temperatures. METHODS: Total
      222 SD rats were randomly divided into control group (PMI=0 h) and four
      experimental groups. And the rats in the experimental groups were sacrificed by
      cervical dislocation and respectively kept at 5 C, 15 C, 25 C and 35 C in a
      controlled environment chamber. The RNA was extracted from brain tissues, which
      was taken at 9 time points from 1 h to 24 h postmortem. The expression levels of
      eight markers, beta-actin, GAPDH, RPS29, 18S rRNA, 5S rRNA, U6 snRNA, miRNA-9 and
      miRNA-125b, were detected using real-time fluorescent quantitative PCR,
      respectively. Proper internal reference was selected by geNorm software.
      Regression analysis of normalized RNA markers was performed by SPSS software.
      Mathematical model for PMI estimation was established using R software. Another 6
      SD rats with known PMI were used to verify the mathematical model. RESULTS: 5S
      rRNA, miR-9 and miR-125b were suitable as internal reference markers for their
      stable expression. Both beta-actin and GAPDH had well time-dependent degradation
      patterns and degraded continually with prolongation of PMI in 24 h postmortem.
      The mathematical model of the variation of DeltaCt values with PMI and
      temperature was set up by R software and the model could be used for PMI
      estimation. The average error rates of model validation using beta-actin and
      GAPDH were 14.1% and 22.2%, respectively. CONCLUSIONS: The expression levels of
      beta-actin and GAPDH are well correlated with PMI and environmental temperature.
      The mathematical model established in present study can provide references for
      estimating early PMI under various temperature conditions.

PMID- 29171733
TI  - Detection of Metabolism Function of Microbial Community of Corpses by Biolog-Eco
      Method.
AB  - OBJECTIVES: To detect the changes of microbial community functional diversity of
      corpses with different postmortem interval (PMI) and to evaluate forensic
      application value for estimating PMI. METHODS: The cultivation of microbial
      community from the anal swabs of a Sus scrofa and a human corpse placed in field
      environment from 0 to 240 h after death was performed using the Biolog-Eco
      Microplate and the variations of the absorbance values were also monitored.
      Combined with the technology of forensic pathology and flies succession, the
      metabolic characteristics and changes of microbial community on the decomposed
      corpse under natural environment were also observed. RESULTS: The diversity of
      microbial metabolism function was found to be negatively correlated with the
      number of maggots in the corpses. The freezing processing had the greatest impact
      on average well color development value at 0 h and the impact almost disappeared
      after 48 h. The diversity of microbial metabolism of the samples became
      relatively unstable after 192 h. The principal component analysis showed that 31
      carbon sources could be consolidated for 5 principal components (accumulative
      contribution ratio >90%).The carbon source tsquare-analysis showed that N-acetyl
      D-glucosamine and L-serine were the dominant carbon sources for estimating the
      PMI (0=240 h) of the Sus scrofa and human corpse. CONCLUSIONS: The Biolog-Eco
      method can be used to reveal the metabolic differences of the carbon resources
      utilization of the microbial community on the corpses during 0-240 h after death,
      which could provide a new basis for estimating the PMI.

PMID- 29171734
TI  - Research on Auditory Long Latency Response in Normal Hearing Subjects.
AB  - OBJECTIVES: To explore the characters and the relationship among latency
      response, amplitude and sound stimulus intensity of auditory long latency
      response(ALR), and to investigate the significance of ALR applied in auditory
      threshold prediction. METHODS: Total 46 subjects (92 ears) with normal hearing
      were tested by ALR. The ALR waves of the subjects were elicited by 5 sound
      stimulus intensity according to the order of 70, 50, 30, 20 and 10 dB nHL. By
      making N1 wave and P2 wave, the values of 3 observed indexes (the latencies of N1
      wave and P2 wave and N1-P2 amplitude) were obtained, and the variation trend of
      the observed indexes were statistically analyzed. The differences in the
      frequency of the indexes were observed. RESULTS: The rate of ALR waves from 46
      subjects (92 ears) with normal hearing was 100%. The latencies of N1 wave and P2
      wave delayed gradually and N1-P2 amplitude declined with sound stimulus intensity
      descending. CONCLUSIONS: In suitable conditions, ALR is a stable technology for
      hearing thresholds prediction. The relation between sound stimulus intensity and
      latency of N1 wave, latency of P2 wave and N1-P2 amplitude of ALR plays an
      important part in auditory thresholds assessment.

PMID- 29171735
TI  - Development of a Fluorescence Multiplex Amplification System with 24 Y-STR Loci.
AB  - OBJECTIVES: To establish a novel multiplex amplification system which comprises
      24 Y-STR loci. METHODS: otal 24 Y-STR gene loci, concluding DYS531, DYS630,
      DYS622, DYS552, DYS510, DYS449, DYS459a/b, DYS446, DYS443, DYS635, DYS587,
      DYS527a/b, DYS460, Y-GATA-A10, DYS520, DYS557, DYS522, DYS481, DYS570, DYS385a/b,
      DYS444, were chosen for establishing the fluorescence multiplex amplification
      system. The specificity, identity, sensitivity, balance of the amplification,
      anti-interference and accuracy of the system were detected and the gene diversity
      was investigated in the population of Guangdong. RESULTS: No band was found in
      nonhuman and female samples that were tested by the established multiplex
      amplification system. The same genotyping results were obtained from different
      tissues of the same person. Complete profiles could be obtained from more than
      0.1 ng of the standard sample 9948. The loss of alleles was found when the common
      inhibitors such as hemoglobin and calcium ion were added 120-200 MUmol/L and 1.5
      2.0 mmol/L respectively to the system which with a strong anti-interference to
      the indigo, humic acid and EDTA. The typing of 24 Y-STR system could give the
      reliable results when 146 unrelated male individuals were detected and compared
      with the Yfiler system parallelly. The haplotype diversity (HD) of the population
      in Guangdong reached 0.999 72 that was better than the result retained from
      Yfiler system, which the HD was 0.998 58. CONCLUSIONS: The fluorescence
      amplification system with 24 Y-STR loci established in present study has a wildly
      application prospect and can be used for cases inspection, paternity tests and Y
      STR database construction.

PMID- 29171736
TI  - SNP in Differentially Methylated Region Upstream of H19 Gene in Guangdong Han
      Population.
AB  - OBJECTIVES: To investigate the single nucleotide polymorphism (SNP) and
      haplotypes in differentially methylated region (DMR) upstream of H19 gene in
      Guangdong Han population. METHODS: The PIA typing and restriction enzyme McrBC
      and HpaII were used to digest the genomic DNA and obtain the individual
      uniparental DNA template strand. The data of uniparental SNP alleles, genotypes
      and haplotypes in DMR upstream of H19 gene were obtained by sequencing. RESULTS:
      A total of 13 SNPs (rs10840167, rs2525883, rs12417375, rs4930101, rs2525882,
      rs2735970, rs2735971, rs11042170, rs2735972, rs10732516, rs2071094, rs2107425,
      and rs4930098) and one mutation locus (g7351c) were found. All loci followed the
      Hardy-Weinberg equilibrium (P>0.05) by statistical analysis. Except for
      rs12417375 (DP=0.279) locus, the DP of remaining 12 SNPs were 0.446-0.614, and
      the g7351c mutation locus (DP=0.013) was the particular loci of the Southern
      Chinese Han population. Eight haplotypes (designated as haplotype 1-8) were
      detected, in which 3 haplotypes had not yet been reported and the DP, PIC, PE and
      H were 0.891, 0.714, 0.524 and 0.758, respectively. CONCLUSIONS: Obtained by PIA
      typing, the SNP in DMR upstream of H19 gene and its haplotypes genetic marker
      system have a high determination power and show a good practical value in
      forensic identification.

PMID- 29171737
TI  - Population Difference Analysis of Allele Frequencies of 24 Y-STR Loci.
AB  - OBJECTIVES: To investigate the population genetic polymorphisms of 24 Y-STR loci
      in unrelated individuals in Eastern Chinese Han population, and to compare the
      difference of Han group between Eastern China and Guangdong. METHODS: The
      population genetics of 24 Y-STR loci in 268 unrelated Han individuals from
      Eastern China were analyzed by GFS 24 Y-STR amplification kit. The allele
      frequencies in Eastern Chinese Han population were compared with the data in
      Guangdong Han population, and the difference analysis between two groups was
      performed. RESULTS: Among the 24 Y-STR loci of 268 unrelated Han individuals from
      Eastern China, 235 alleles and 267 haplotypes were observed. GD value ranged from
      0.564 9 to 0.966 8. The difference between 12 loci (DYS622, DYS552, DYS443, et
      al.) of Han population in Eastern China and in Guangdong was statistically
      significance. CONCLUSIONS: GFS 24Y STR amplification system shows favorable
      polymorphisms, which can be used in patrilineal genetic relationship
      identification.

PMID- 29171738
TI  - Recognition of Y Fragment Deletion by Genotyping Graphs after Amplified by
      PowerPlex(r) 21 Detection Kit.
AB  - OBJECTIVES: To recognize the possibility of Y fragment deletion of Amelogenin
      gene intuitively and simply according to the genotyping graphs. METHODS: By
      calculating the ratio of total peak height of genotyping graphs, the statistics
      of equilibrium distribution between Amelogenin and D3S1358 loci, Amelogenin X
      gene and Amelogenin Y-gene, and different alleles of D3S1358 loci from 1 968
      individuals was analyzed after amplified by PowerPlex(r) 21 detection kit.
      RESULTS: Sum of peak height of Amelogenin X allele was not less than 60% that of
      D3S1358 loci alleles in 90.8% female samples, and sum of peak height of
      Amelogenin X allele was not higher than 70% that of D3S1358 loci alleles in 94.9%
      male samples. CONCLUSIONS: The result of genotyping after amplified by
      PowerPlex(r) 21 detection kit shows that the possibility of Y fragment deletion
      should be considered when only Amelogenin X-gene of Amelogenin is detected and
      the peak height of Amelogenin X-gene is not higher than 70% of the total peak
      height of D3S1358 loci.

PMID- 29171739
TI  - Application of Finite Element Method in Traffic Injury and Its Prospect in
      Forensic Science.
AB  - The finite element method (FEM) is a numerical computation method based on
      computer technology, and has been gradually applied in the fields of medicine and
      biomechanics. The finite element analysis can be used to explore the loading
      process and injury mechanism of human body in traffic injury. FEM is also helpful
      for the forensic investigation in traffic injury. This paper reviews the
      development of the finite element models and analysis of brain, cervical spine,
      chest and abdomen, pelvis, limbs at home and aboard in traffic injury in recent
      years.

PMID- 29171740
TI  - Progress on Post Traumatic Epilepsy and Its Forensic Evaluation.
AB  - Post traumatic epilepsy (PTE) refers to the epileptic seizures after traumatic
      brain injury. Organic damage can be found by imaging examination, and abnormal
      electroencephalogram can be detected via electroencephalogram examination which
      has the similar location of the brain injury. PTE has the characteristics of low
      incidence, absence of case reports, and easy to exaggerate the state of illness,
      which add difficulties to the forensic identification. This paper reviews the
      status of epidemiology, pathogenesis, clinical treatment and forensic
      identification for PTE.

PMID- 29171741
TI  - Source Identification of Human Biological Materials and Its Prospect in Forensic
      Science.
AB  - Source identification of human biological materials in crime scene plays an
      important role in reconstructing the crime process. Searching specific genetic
      markers to identify the source of different human biological materials is the
      emphasis and difficulty of the research work of legal medical experts in recent
      years. This paper reviews the genetic markers which are used for identifying the
      source of human biological materials and studied widely, such as DNA methylation,
      mRNA, microRNA, microflora and protein, etc. By comparing the principles and
      methods of source identification of human biological materials using different
      kinds of genetic markers, different source of human biological material owns
      suitable marker types and can be identified by detecting single genetic marker or
      combined multiple genetic markers. Though there is no uniform standard and method
      for identifying the source of human biological materials in forensic laboratories
      at present, the research and development of a series of mature and reliable
      methods for distinguishing different human biological materials play the role as
      forensic evidence which will be the future development direction.

PMID- 29171742
TI  - [Microsoft(r) Power BI tool for presentation of antimicrobial consumption data].

PMID- 29171743
TI  - [Bartholinitis due to Streptococcus pneumoniae].

PMID- 29171744
TI  - [External otitis due Turicella otitidis: two case reports].

PMID- 29171745
TI  - Retracted: Resveratrol inhibits oesophageal adenocarcinoma cell proliferation via
      AMP-activated protein kinase signaling
AB  - Retraction: Retracted:Resveratrol inhibits oesophageal adenocarcinoma cell
      proliferation via AMP-activated protein kinase signaling Asian Pacific Journal of
      Cancer Prevention (APJCP) has retracted the article titled "Resveratrol Inhibits
      Oesophageal Adenocarcinoma Cell Proliferation via AMP-activated Protein Kinase
      Signaling"(1) for reason of having duplicated contents brought to the attention
      of APJCP's editorial office by the following email content:"Dear Editors of
      Gastroenterology and Hepatology, Acta Pharmacologica Sinica, Asian Pac J Cancer
      Prev, Clinical and Experimental Hypertension, I write to you from the editorial
      office of PLOS ONE to inform you of concerns related to duplicated content in
      articles published by your journals. We have been following up on concerns of
      overlapping text and duplicate Western blots within the following PLOS ONE
      article: [1] Berberine Improves Kidney Function in Diabetic Mice via AMPK
      Activation    https://doi.org/10.1371/journal.pone.0113398Received: June 9, 2014;
      Accepted: October 23, 2014; Published: November 19, 2014 It was initially brought
      to our attention that there is duplication of Western blot images between the
      PLOS ONE article and the following published papers: [2] Brain Injury (Received
      28 Oct 2013, Accepted 4 Jan 2015, Published online 20 Mar 2015) doi:
      10.3109/02699052.2015.1004746: Figure 6b GAPDH is similar to Figure 2A AMPK in
      [1]  [3] Exp Mol Pathol (Received 24 Feb 2014, Accepted 10 Sep 2014, Available
      online 16 Sep 2014) doi:10.1016/j.yexmp.2014.09.006: Figure 5B GAPDH is similar
      to Figure 2A AMPK in [1]; Figure 5C Occludin is similar to Figure 2A LKB1 in [1] 
      [4] Korean J Physiol Pharmacol, (Received 7 Nov 2013, Accepted 3 Jan 2016) doi:
      10.4196/kjpp.2016.20.4.325 RETRACTED: Figure 6B GAPDH is similar to Figure 2A
      AMPK [1]  Please note that the KJPP paper has been retracted as a result of the
      content duplication issues. During the course of our follow up, we have
      discovered additional instances of possible duplication as follows:  [5]
      Gastroenterology and Hepatology (Accepted 6 Aug 2014, Accepted ms online 28 Aug
      2014, Published 23 Feb 2015) doi:10.1111/jgh.12723: Figure 1d AMPK is similar to
      Figure 2A AMPK in [1], Figure 3a iNOS is similar to Figure 2A LKB1 in [1]  [6]
      Acta Pharmacologica Sinica (Received 4 Mar 2014, Accepted 28 July 2014, Published
      17 Nov 2014) doi: 10.1038/aps.2014.88: Figure 1 A and B bar charts are similar to
      Figure 1 A and B bar charts in [1], Figure 1E AMPK is similar to Figure 2A AMPK
      in [1], Figure 1E p-AMPK is similar to Figure 2A P-AMPK in [1], Figure 1E bar
      chart is similar to the Figure 2A bar chart in [1]  [7] Asian Pac J Cancer Prev
      (Published Jan 2014) doi: 10.7314/APJCP.2014.15.2.677: Figure 3A GAPDH is similar
      to Figure 2A AMPK in [1] and p27 kip1 is similar to Figure 2A P-AMPK in [1] [8]
      Clinical and Experimental Hypertension (Received 15 Sep 2015, Accepted 24 Nov
      2015, Published 5 May 2016) doi: 10.3109/10641963.2015.1131288: Figure 2A LKB1
      and P-AMPK are similar to Figure 2A LKB1 and P-AMPK in [1], Figure 2B P-AMPK and
      AMPK are similar to Figure 2B P-AMPK and AMPK in [1], Figure 2A and B bar charts
      appear similar in both articles. Figures 1A, B and C including Western blots and
      charts appear similar in both articles. Figure 6C AMPK is similar to Figure 2A
      AMPK in [1] (note that authors Min Hu and Bo Liu may be the same as authors on
      the retracted KJPP paper above) Articles [5], [6], [7], and [8] contain various
      amounts of duplicated text in the Results sections when compared to the PLOS ONE
      article. Note that there may be other instances of duplicated data and/or text
      between the above articles aside from those affecting the PLOS ONE article. For
      at least some of the duplicated text, it appears that some of the manuscripts
      were under consideration at overlapping times. We have been informed that an
      external biotechnology company conducted the Western blot experiments and
      provided the raw blots to the authors for the PLOS ONE paper. How the
      duplications in text and figures arose remains unresolved. Although our
      correspondence with the authors about this matter is ongoing, we have determined
      that it is appropriate to issue a retraction of the PLOS ONE article, and the
      retraction notice will provide details of the similarities in content with the
      above-listed articles. We will also report this matter to the PLOS ONE authors'
      institution. I hope that the information provided above is helpful. If you have
      any questions in the course of any follow up on this matter, please do not
      hesitate to get in touch. Best wishes,  References:   Guang-Hua Fan, Zhong-Ming
      Wang, Xi Yang, Li-Ping Xu, Qin Qin, Chi Zhang, Jian-Xin Ma, Hong-Yan Cheng, Xin
      Chen Sun.  Resveratrol Inhibits Oesophageal Adenocarcinoma Cell Proliferation via
      AMP-activated Protein Kinase Signaling.  Asian Pac J Cancer Prev, 15 (2), 677-682

PMID- 29171746
TI  - Enantioselective Synthesis of beta-Allenoates via Phosphine-Catalyzed and ZnI2
      Promoted Preparation of Oxazolidines and Propargylamines Using Chiral Amines, 1
      Alkynes, and Propiolates.
AB  - Diphenylphosphinoethane (DPPE)-catalyzed and ZnI2-promoted in situ formation of
      oxazolidine, alkynyl zinc, and propargylamine intermediates from 1-alkynes,
      chiral (S)-diphenyl(pyrrolidin-2-yl)methanol, and propiolates gave the
      corresponding chiral (R)-beta-allenoates in 40-72% yield with up to >99% ee. The
      intermediate propargylamine was isolated in 50% yield and converted to give the
      beta-allenoate 10aa in 68% yield and 96% ee upon reaction with ZnI2. The results
      are discussed considering a mechanism involving oxazolidine and iminium ions
      formed in situ followed by addition of alkynyl zinc complex to produce the
      propargylamine that gives the corresponding allenoate via a 1,5-hydrogen shift in
      the presence of ZnI2.

PMID- 29171747
TI  - Functional 1,8-Naphthalimide AIE/AIEEgens: Recent Advances and Prospects.
AB  - This comprehensive review surveys the up-to-date development of aggregation
      induced emission/aggregation-induced emission enhancement (AIE/AIEE) active
      naphthalimide (NI)-based smart materials with potential for wide and real-world
      applications and that serves as a highly versatile building block with tunable
      absorption and emission in the complete visible region. The review article
      commences with a precise description of the importance of NI moiety and its
      several restricted area of applications owing to its aggregation caused quenching
      (ACQ) properties, followed by the discovery and importance of AIE/AIEE-active
      NIs. The introduction section tracked an overview of the state of the art in NI
      luminogens in multiple applications. It also includes a few mechanistic studies
      on the structure-property correlation of NIs and provides more insights into the
      condensed-state photophysical properties of small aggregation-prone systems. The
      review aims to ultimately accomplish current and forthcoming views comprising the
      use of the NIs for the detection of biologically active molecules, such as amino
      acids and proteins, recognition of toxic analytes, fabrication of light emitting
      diodes, and their potential in therapeutics and diagnostics.

PMID- 29171748
TI  - Sensitivities of Simulated Source Contributions and Health Impacts of PM2.5 to
      Aerosol Models.
AB  - Chemical transport models are useful tools for evaluating source contributions
      and health impacts of PM2.5 in the atmosphere. We recently found that
      concentrations of PM2.5 compounds over Japan were much better reproduced by a
      volatility basis set model with an enhanced dry deposition velocity of HNO3 and
      NH3 compared with a two-product yield model. In this study, we evaluated the
      sensitivities to organic aerosol models of the simulated source contributions to
      PM2.5 concentrations and of PM2.5-related mortality. Overall, the simulated
      source contributions to PM2.5 were similar between the two models. However,
      because of the improvements associated with the volatility basis set model, the
      contributions of ammonia sources decreased, particularly in winter and spring,
      and contributions of biogenic and stationary evaporative sources increased in
      spring and summer. The improved model estimated that emission sources in Japan
      contributed 35%-48% of the PM2.5-related mortality in Japan. These values were
      higher than the domestic contributions to average PM2.5 concentrations in Japan
      (26%-33%) because the domestic contributions were higher in higher population
      areas. These results indicate that control of both domestic and foreign emissions
      is necessary to reduce health impacts due to PM2.5 in Japan.

PMID- 29171749
TI  - Au-Protected Ag Core/Satellite Nanoassemblies for Excellent Extra-/Intracellular
      Surface-Enhanced Raman Scattering Activity.
AB  - Silver nanoparticles (AgNPs) and their assembled nanostructures such as
      core/satellite nanoassemblies are quite attractive in plasmonic-based
      applications. However, one biggest drawback of the AgNPs is the poor chemical
      stability which also greatly limits their applications. We report fine Au coating
      on synthesized quasi-spherical silver nanoparticles (AgNSs) with few atomic
      layers to several nanometers by stoichiometric method. The fine Au coating layer
      was confirmed by energy-dispersive X-ray spectroscopy elemental mapping and
      aberration-corrected high-angle annular dark-field scanning transmission electron
      microscopy. The optimized minimal thickness of Au coating layer on different
      sized AgNSs (22 nm Ag@0.9 nm Au, 44 nm Ag@1.8 nm Au, 75 nm Ag@2.9 nm Au, and 103
      nm Ag@0.9 nm Au) was determined by extreme chemical stability tests using H2O2,
      NaSH, and H2S gas. The thin Au coating layer on AgNSs did not affect their
      plasmonic-based applications. The core/satellite assemblies based on Ag@Au NPs
      showed the comparable SERS intensity and uniformity three times higher than that
      of noncoated Ag core/satellites. The Ag@Au core/satellites also showed high
      stability in intracellular SERS imaging for at least two days, while the SERS of
      the noncoated Ag core/satellites decayed significantly. These spherical Ag@Au NPs
      can be widely used and have great advantages in plasmon-based applications,
      intracellular SERS probes, and other biological and analytical studies.

PMID- 29171750
TI  - An All-Phosphate and Zero-Strain Sodium-Ion Battery Based on Na3V2(PO4)3 Cathode,
      NaTi2(PO4)3 Anode, and Trimethyl Phosphate Electrolyte with Intrinsic Safety and
      Long Lifespan.
AB  - Development of intrinsically safe and long lifespan sodium-ion batteries (SIBs)
      is urgently needed for large-scale energy storage applications. However, most of
      the currently developed SIBs suffer from insufficient cycle life and potential
      unsafety. Herein, we construct an all-phosphate sodium-ion battery (AP-SIB) using
      a Na3V2(PO4)3 cathode, NaTi2(PO4)3 anode, and nonflammable trimethyl phosphate
      (TMP) electrolyte. The AP-SIB exhibits not only high safety, high rate
      performance, and ultralong cycle life but also zero-strain characteristics due to
      the inverse volume change of the phosphate cathode and anode during charge and
      discharge cycles, offering a safer and cycle-stable Na-ion technology for
      electric storage applications.

PMID- 29171751
TI  - From Cellulose Nanospheres, Nanorods to Nanofibers: Various Aspect Ratio Induced
      Nucleation/Reinforcing Effects on Polylactic Acid for Robust-Barrier Food
      Packaging.
AB  - The traditional approach toward improving the crystallization rate as well as the
      mechanical and barrier properties of poly(lactic acid) (PLA) is the incorporation
      of nanocelluloses (NCs). Unfortunately, little study has been focused on the
      influence of the differences in NC morphology and dimensions on the PLA property
      enhancement. Here, by HCOOH/HCl hydrolysis of lyocell fibers, microcrystalline
      cellulose (MCC), and ginger fibers, we unveil the preparation of cellulose
      nanospheres (CNS), rod-like cellulose nanocrystals (CNC), and cellulose
      nanofibers (CNF) with different aspect ratios, respectively. All the NC surfaces
      were chemically modified by Fischer esterification with hydrophobic formate
      groups to improve the NC dispersion in the PLA matrix. This study systematically
      compared CNS, CNC, and CNF as reinforcing agents to induce different kinds of
      heterogeneous nucleation and reinforce the effects on the properties of PLA. The
      incorporation of three NCs can greatly improve the PLA crystallization ability,
      thermal stability, and mechanical strength of nanocomposites. At the same NC
      loading level, the PLA/CNS showed the highest crystallinity (19.8 +/- 0.4%) with
      a smaller spherulite size (33 +/- 1.5 MUm), indicating that CNS, with its high
      specific surface area, can induce a stronger heterogeneous nucleation effect on
      the PLA crystallization than CNC or CNF. Instead, compared to PLA, the PLA/CNF
      nanocomposites gave the largest Young's modulus increase of 350 %, due to the
      larger aspect ratio/rigidity of CNF and their interlocking or percolation network
      caused by filler-matrix interfacial bonds. Furthermore, taking these factors of
      hydrogen bonding interaction, increased crystallinity, and interfacial tortuosity
      into account, the PLA/CNC nanocomposite films showed the best barrier property
      against water vapor and lowest migration levels in two liquid food simulates
      (well below 60 mg kg-1 for required overall migration in packaging) than CNS- and
      CNF-based films. This comparative study was very beneficial for selecting
      reasonable nanocelluloses as nucleation/reinforcing agents in robust-barrier
      packaging biomaterials with outstanding mechanical and thermal performance.

PMID- 29171752
TI  - Solution-Processed Flexible Organic Ferroelectric Phototransistor.
AB  - In this article, we demonstrate ferroelectric insulator, P(VDF-TrFE), can be
      integrated with red light sensitive polymeric semiconductor, P(DPP-TzBT), toward
      ferroelectric organic phototransistors (OPTs). This ferroelectricity-modulated
      phototransistor possesses different nonvolatile and tunable dark current states
      due to P(VDF-TrFE)'s remnant polarization. As a result, the OPT is endowed with a
      tunable dark current level ranging from 1 nA to 100 nA. Once the OPT is
      programmed or electrically polarized, its photo-to-dark (signal-to-noise) ratio
      can be "flexible" during photodetection process, without gate bias application.
      This kind of organic ferroelectric phototransistor has great potential in
      detecting wide ranges of light signals with good linearity. Moreover, its tuning
      mechanism discussed in this work can be helpful to understand the operation
      mechanism of organic phototransistor (OPT). It can be promising for novel
      photodetection application in plastic electronic devices.

PMID- 29171753
TI  - A Stepwise Approach for the Synthesis of Folic Acid Conjugates with Protein
      Kinase Inhibitors.
AB  - Herein, we report an alternative synthetic approach for selected 2,6,9
      trisubstituted purine CDK inhibitor conjugates with folic acid as a drug-delivery
      system targeting folate receptors. In contrast to the previously reported
      approaches, the desired conjugates were constructed stepwise using solid-phase
      synthesis starting from immobilized primary amines. The ability of the prepared
      conjugates to release the free drug was verified using dithiothreitol (DTT) and
      glutathione (GSH) as liberating agents. Finally, binding to the folate receptor
      (FOLR1) overexpressed in a cancer cell line was measured by flow cytometry using
      a fluorescent imaging probe.

PMID- 29171754
TI  - Palladium Catalyzed C-I and Vicinal C-H Dual Activation of Diaryliodonium Salts
      for Diarylations: Synthesis of Triphenylenes.
AB  - Using the synthetic strategy of palladium-catalyzed dual activation of both C-I
      and vicinal C-H bonds of diaryliodonium salts, we report an approach for direct
      diarylations of 2-bromobiphenyls or bromobenzenes. As a result, a wide range of
      triphenylenes with various substituents have been synthesized in good yields.
      These triphenylenes are expected to be employed in the "bottom-up" synthesis of
      functional aromatic molecules in material science.

PMID- 29171755
TI  - Conformational Preferences of the Phenyl Group in 1-Phenyl-1-X-1-silacyclo
      hexanes (X = MeO, HO) and 3-Phenyl-3-X-3-silatetrahydropyrans (X = HO, H) by Low
      Temperature 13C NMR Spectroscopy and Theoretical Calculations.
AB  - New Si-phenyl-substituted silacyclohexanes and 3-silatetrahydropyrans have been
      synthesized and studied with respect to the conformational equilibria of the
      heterosix-membered ring by low temperature 13C NMR spectroscopy and quantum
      chemical calculations. For 1-methoxy-1-phenylsilacyclohexane 1 and 3-phenyl-3
      silatetrahydropyran 4 the conformational equilibria could be frozen and assigned.
      The Phax ? Pheq equilibrium constants at 103 K are 2.21 for 1 and 4.59 for 4. In
      complete agreement with former studies of similar silicon compounds, molecules 1
      and 4 prefer to adopt the Pheq conformation. The conformational equilibria of 1
      hydroxy-1-phenylsilacyclohexane 2 and 3-hydroxy-3-phenyl-3-silatetrahydropyran 3
      could not be frozen at 100 K and proved to be heavily one-sided (if not
      anancomeric). Obviously, there is a general trend of predominance of Phax
      conformer in the gas phase and of Pheq in solution. For the isolated molecules of
      silanols 2 and 3, calculations allowed to explain the axial predominance of the
      phenyl group by a larger polarization of the Si-Ph than of the Si-O bond in the
      Phax conformer and additional destabilization of 3-Pheq conformer by repulsion of
      unidirectional dipoles of the endocyclic oxygen lone pair and of the highly polar
      axial Si-O bond.

PMID- 29171756
TI  - Nitrogen Oxides and Nitric Acid Enable the Sustainable Hydroxylation and
      Nitrohydroxylation of Benzenes under Visible Light Irradiation.
AB  - A new type of waste recycling strategy is described in which nitrogen oxides or
      nitric acid are directly employed in photocatalyzed hydroxylations and
      nitrohydroxylations of benzenes. Through these transformations, otherwise costly
      denitrification can be combined with the synthesis of valuable compounds for
      various applications.

PMID- 29171757
TI  - Impedimetric Sensor of ss-HSDNA/Reduced Graphene Oxide Aerogel Electrode toward
      Aflatoxin B1 Detection: Effects of Redox Mediator Charges and Hydrodynamic
      Diffusion.
AB  - Here, an impedimetric biosensor for determination and quantification of an
      aflatoxin B1 (AFB1) level using a reduced graphene oxide aerogel labeled with a
      single strand DNA (ss-HSDNA/rGOae) modified on a rotating disk electrode (RDE) is
      presented. Owing to the large biomolecule biding on the electrode, an electron
      transfer is interrupted and not easily accessible to a target molecule. To
      address this issue, we aim to study two effects; one considers electro-redox
      mediators and the other considers the hydrodynamic effect. By observing a cyclic
      voltammetric response from the ss-HSDNA/rGOae electrode in three different
      charges of the redox mediators (i.e., neutral FcCH2OH, cationic Ru(NH3)63+, and
      anionic Fe(CN)64-) in a phosphate buffer solution (PBS) containing AFB1, the
      magnitude of anodic current at 50 mV s-1 is 825, 615, and 550 mA cm-1,
      respectively, which is significant dominated by the charge of the redox probe.
      The effect of hydrodynamic diffusion of the ss-HSDNA/rGOae rotating disk
      electrode (RDE) toward AFB1 detection using FcCH2OH as the redox mediator was
      recorded by applying a range of rotating speed from 500 to 4000 rpm. Increasing
      rotating speed reduces the charge transfer resistance resulting in the lower
      detectable level for AFB1 quantification. In the case of 4000 rpm, the AFB1 can
      be detected with a limit of detection of 0.04 ng/mL and a linear range of 1 * 10
      10 to 7 * 10-8g/mL.

PMID- 29171758
TI  - Toward best practices in data processing and analysis for intact biotherapeutics
      by MS in quantitative bioanalysis.
AB  - AIM: Typically, quantitation of biotherapeutics from biological matrices by LC-MS
      is based on a surrogate peptide approach to determine molecule concentration.
      Recent efforts have focused on quantitation of the intact protein molecules or
      larger mass subunits of monoclonal antibodies. To date, there has been limited
      guidance for large or intact protein mass quantitation for quantitative
      bioanalysis. METHODOLOGY: Intact- and subunit-level analyses of biotherapeutics
      from biological matrices are performed at 12-25 kDa mass range with quantitation
      data presented. RESULTS: Linearity, bias and other metrics are presented along
      with recommendations made on the viability of existing quantitation approaches.
      CONCLUSION: This communication is intended to start a discussion around intact
      protein data analysis and processing, recognizing that other published
      contributions will be required.

PMID- 29171759
TI  - Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug
      discovery, development and safety.
AB  - This review discusses the use of stable (13C, 2D) or radioactive isotopes (14C,
      11C, 18F, 131I, 64Cu, 68Ga) incorporated into the molecular structure of new drug
      entities for the purpose of pharmacokinetic or -dynamic studies. Metabolite in
      safety testing requires the administration of pharmacologically active doses. In
      such studies, radiotracers find application mainly in preclinical animal
      investigations, whereby LC-MS/MS is used to identify metabolite structure and
      drug-related effects. In contrast, first-in-human metabolite studies have to be
      carried out at nonpharmacological doses not exceeding 100 MUg (microdose), which
      is generally too low for metabolite detection by LC-MS/MS. This short-coming can
      be overcome by specific radio- or isotopic labeling of the drug of interest and
      measurements using accelerator mass spectroscopy, single-photon emission computed
      tomography and positron emission tomography. Such combined radioisotope-based
      approaches permit Phase 0, first-in-human metabolite study.

PMID- 29171760
TI  - Analytical considerations for quantitative LC-MS strategies for measuring
      antibody drug-target engagement in tissues.

PMID- 29171761
TI  - New agents for the management of resistant metastatic breast cancer.
AB  - INTRODUCTION: Metastatic breast cancer (MBC) is an incurable disease and
      treatment is directed towards symptom palliation and survival prolongation.
      Treatment selection in patients is based on tumor biology, age, comorbidities,
      performance status, tumor burden, and prior treatment history. Areas covered:
      This present review summarizes the recent treatment strategies in the management
      of MBC, highlighting regimens after first-line therapy. Topics discussed include
      new strategies for endocrine therapy, anti-HER2 therapy, and promising strategies
      for the management of triple negative breast cancer. Expert opinion: MBC is a
      heterogeneous entity and despite recent advances, there is significant room for
      improvement of treatment beyond first-line therapies. Combination regimens that
      can maximize clinical efficacy while minimizing toxicities are required. Current
      investigation approaches in advanced stages of clinical development include
      immunoconjugates, immune checkpoint blockade, novel cyclin-dependent-kinase
      inhibitors, and PARP inhibitors for MBC associated with germline BRCA mutations.
      We recommend that every patient with MBC should be evaluated for clinical trial
      options.

PMID- 29171763
TI  - Correction to: Pascoe et al., Beyond lip service: Towards human rights-driven
      guidelines for South African speech-language pathologists.

PMID- 29171762
TI  - PLK4: a link between centriole biogenesis and cancer.
AB  - INTRODUCTION: Polo like kinase (PLK) is known to play a pivotal role in various
      cell cycle processes to perpetuate proper division and growth of the cells. Polo
      like kinase-4 (PLK4) is one such kinase that appears in low abundance and plays a
      well-characterized role in centriole duplication. PLK4 deregulation (i.e. both
      overexpression and depletion of PLK4), leads to altered mitotic fidelity and
      thereby triggers tumorigenesis. Hence, over the last few years PLK4 has emerged
      as a potential therapeutic target for the treatment of various advanced cancers.
      Areas covered: In this review, we discuss the basic structure, expression,
      localization and functions of PLK4 along with its regulation by various proteins.
      We also discuss the role of altered PLK4 activity in the onset of cancer and the
      current pre-clinical and clinical inhibitors to regulate PLK4. Expert opinion:
      PLK4 mediated centriole duplication has a crucial role in maintaining mitotic
      correctness in normal cells, while its deregulation has a greater impact on
      genesis of cancer. Henceforth, a deep knowledge of the PLK4 levels, its role and
      interactions with various proteins in cancer is required to design effective
      inhibitors for clinical use.

PMID- 29171764
TI  - Loneliness and social isolation among young and late middle-age adults:
      Associations with personal networks and social participation.
AB  - OBJECTIVE: Associations between social networks and loneliness or social
      isolation are well established among older adults. Yet, limited research examines
      personal networks and participation on perceived loneliness and social isolation
      as distinct experiences among younger adults. Accordingly, we explore
      relationships among objective and subjective measures of personal networks with
      loneliness and isolation, comparing a younger and older cohort. METHODS: The UC
      Berkeley Social Networks Study offers unique cohort data on young (21-30 years
      old, n = 472) and late middle-age adults' (50-70 years old, n = 637) personal
      network characteristics, social participation, network satisfaction, relationship
      status, and days lonely and isolated via online survey or in-person interview.
      Negative binomial regression models were used to examine associations between
      social network characteristics, loneliness, and isolation by age group. RESULTS:
      Young adults reported twice as many days lonely and isolated than late middle-age
      adults, despite, paradoxically, having larger networks. For young adults,
      informal social participation and weekly religious attendance were associated
      with fewer days isolated. Among late middle-age adults, number of close kin and
      relationship status were associated with loneliness. Network satisfaction was
      associated with fewer days lonely or isolated among both age groups. CONCLUSION:
      Distinct network characteristics were associated with either loneliness or
      isolation for each cohort, suggesting network factors are independently
      associated with each outcome, and may fluctuate over time. Network satisfaction
      was associated with either loneliness or isolation among both cohorts, suggesting
      perceptions of social networks may be equally important as objective measures,
      and remain salient for loneliness and isolation throughout the life course.

PMID- 29171765
TI  - Serine protease inhibitors to treat inflammation: a patent review (2011-2016).
AB  - INTRODUCTION: Inflammation is a physiological part of the complex biological
      response of tissues to counteract various harmful signals. This process involves
      diverse actors such as immune cells, blood vessels, and nerves as sources of
      mediators for inflammation control. Among them serine proteases are key elements
      in both physiological and pathological inflammation. Areas covered: Serine
      protease inhibitors to treat inflammatory diseases are being actively
      investigated by various industrial and academic institutions. The present review
      covers patent literature on serine protease inhibitors for the therapy of
      inflammatory diseases patented between 2011 and 2016. Expert opinion: Serine
      proteases regulating inflammation are versatile enzymes, usually involved in
      proinflammatory cytokine production and activation of immune cells. Their
      dysregulation during inflammation can have devastating consequences, promoting
      various diseases including skin and lung inflammation, neuroinflammation, and
      inflammatory arthritis. Several serine proteases were selected for their
      contribution to inflammatory diseases and significant efforts that are spread to
      develop inhibitors. Strategies developed for inhibitor identification consist on
      either peptide-based inhibitor derived from endogenous protein inhibitors or
      small-organic molecules. It is also worth noting that among the recent patents on
      serine protease inhibitors related to inflammation a significant number are
      related to retinal vascular dysfunction and skin diseases.

PMID- 29171766
TI  - Bioanalytical methods for the detection of antidiabetic drugs: a review.
AB  - Type 2 diabetes mellitus, a disease which prevalence has been progressively
      increasing worldwide, is characterized by chronic hyperglycemia resulting from
      the combination of inappropriate insulin secretion and/or resistance to insulin
      action. If left uncontrolled, diabetes is associated with complications such as
      dysfunction and failure of various organs, and even premature death. Along with
      lifestyle-modification strategies, several classes of oral antidiabetic agents
      can be employed for glycemic control. Thus, therapeutic drug monitoring of these
      drugs is essential to maintain appropriate treatment. This review discusses the
      most frequently employed analytical techniques and sample preparation systems to
      obtain a reliable and trustworthy method to quantify antidiabetic drugs in
      biological matrices. An adequate choice of internal standard, ideal
      chromatography conditions and most suitable analytical detector are reported.

PMID- 29171767
TI  - Can intercalating chemotherapy with epidermal growth factor receptor inhibitors
      delay development of treatment resistance in advanced non-small cell lung cancer?

PMID- 29171768
TI  - Matrix effects and application of matrix effect factor.

PMID- 29171769
TI  - Alirocumab for the treatment of hyperlipidemia in high-risk patients: an updated
      review.
AB  - INTRODUCTION: Alirocumab is a fully human immunoglobulin G1 monoclonal antibody
      directed against proprotein convertase subtilisin/kexin type 9 (PCSK9) approved
      for the treatment of hypercholesterolemia in high-risk patients. The objective is
      to provide an updated review of the recent data published for alirocumab. Areas
      covered: The efficacy and safety of alirocumab has been initially evaluated in a
      comprehensive phase 3 program conducted in more than 6 000 patients with primary
      non-familial and heterozygous familial hypercholesterolemia: alirocumab reduced
      LDL-cholesterol up to 62% in phase 3 with every 2-week dosing compared with
      placebo, and up to 36% compared with ezetimibe, with an excellent safety and
      tolerability profile. Herein, the author describes new efficacy and safety data
      obtained from complementary analyses of the phase 3 program submitted for
      approval and reports data from new specific trials. Expert commentary: Based on
      current high pricing, the patient groups prioritized for alirocumab treatment are
      patients with heterozygous familial hypercholesterolemia and patients with
      atherosclerotic cardiovascular disease who have substantially elevated LDL
      cholesterol on maximally tolerated statin plus ezetimibe therapy. The ongoing
      ODYSSEY OUTCOMES trial will provide important information on the cost
      effectiveness of alirocumab treatment.

PMID- 29171770
TI  - Emerging biomarkers of lymphangioleiomyomatosis.
AB  - INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a destructive lung disease
      affecting primarily women. LAM is caused by inactivating mutations in the
      tuberous sclerosis complex (TSC) genes, resulting in hyperactivation of
      mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Over the past five
      years, there have been remarkable advances in the diagnosis and therapy of LAM,
      including the identification of vascular endothelial growth factor D (VEGF-D) as
      a diagnostic biomarker and the US Food and Drug Administration approval of
      sirolimus as therapy for LAM. In appropriate clinical situations VEGF-D testing
      can make lung biopsy unnecessary to diagnose LAM. However, there remains an
      urgent unmet need for additional biomarkers of disease activity and/or response
      to therapy. Areas covered: This work reviews VEGF-D, an established LAM
      biomarker, and discusses emerging biomarkers, including circulating LAM cells,
      imaging, lipid, and metabolite biomarkers, focusing on those with the highest
      potential impact for LAM patients. Expert commentary: Ongoing research priorities
      include the development of validated biomarkers to 1) noninvasively diagnose LAM
      in women whose VEGF-D levels are not diagnostic, 2) accurately predict the
      likelihood of disease progression and 3) quantitatively measure disease activity
      and LAM cell burden. These biomarkers would enable personalized, precision
      clinical care and fast-track clinical trial implementation, with high clinical
      impact.

PMID- 29171771
TI  - ICP-MS determination of serum aluminum in monkeys subcutaneously administered an
      alhydrogel-formulated drug candidate.
AB  - AIM: To develop and validate an inductively coupled plasma-mass spectrometry
      method for quantitative bioanalysis of aluminum (Al) in monkey serum in support
      of a GLP TOX study with alhydrogel-formulated drug candidate. METHODS & RESULTS:
      The method was linear over a dynamic range of 10-1000 ng/ml using a 50-MUl sample
      volume. The intra-/inter-run precision (%CV) of the quality control sample
      results were <=7.9% (CV) and the accuracy (%bias) within +/-11.0% across all
      quality control concentrations evaluated. Other validation parameters, including
      stability under various conditions, extraction recovery and matrix effect, all
      met the acceptance criteria. CONCLUSION: The validated method was successfully
      implemented for the quantitative analysis of Al in monkey serum to assess the
      systemic exposure to Al.

PMID- 29171772
TI  - Assessing gaps in cholesterol treatment guidelines for primary prevention of
      cardiovascular disease based on available randomised clinical trial evidence: The
      Rotterdam Study.
AB  - Background The purpose of this study was to determine how American College of
      Cardiology/American Heart Association (ACC/AHA) 2013 and European Society of
      Cardiology 2016 guidelines for the primary prevention of atherosclerotic
      cardiovascular disease (CVD) compare in reflecting the totality of accrued
      randomised clinical trial evidence for statin treatment at population level.
      Methods From 1997-2008, 7279 participants aged 45-75 years, free of
      atherosclerotic cardiovascular disease, from the population-based Rotterdam Study
      were included. For each participant, we compared eligibility for each one of 11
      randomised clinical trials on statin use in primary prevention of CVD, with
      recommendations on lipid-lowering therapy from the ACC/AHA and European Society
      of Cardiology (ESC) guidelines. Atherosclerotic cardiovascular disease incidence
      and cardiovascular disease mortality rates were calculated. Results The
      proportion of participants eligible for each trial ranged from 0.4% for ALLHAT
      LLT to 30.8% for MEGA. The likelihood of being recommended for lipid-lowering
      treatment was lowest for those eligible for low-to-intermediate risk RCTs (HOPE
      3, MEGA, and JUPITER), and highest for high-risk individuals with diabetes
      (MRC/BHF HPS, CARDS, and ASPEN) or elderly PROSPER. Eligibility for an increasing
      number of randomised clinical trials correlated with a greater likelihood of
      being recommended lipid-lowering treatment by either guideline ( p < 0.001 for
      both guidelines). Conclusion Compared to RCTs done in high risk populations,
      randomised clinical trials targeting low-to-intermediate risk populations are
      less well-reflected in the ACC/AHA, and even less so in the ESC guideline
      recommendations. Importantly, the low-to-intermediate risk population targeted by
      HOPE-3, the most recent randomised clinical trial in this field, is not well
      captured by the current European prevention guidelines and should be specifically
      considered in future iterations of the guidelines.

PMID- 29171773
TI  - Fitness attenuates the prevalence of increased coronary artery calcium in
      individuals with metabolic syndrome.
AB  - Background The association between cardiorespiratory fitness, physical activity
      and coronary artery calcium (CAC) is unclear, and whether higher levels of
      fitness attenuate CAC prevalence in subjects with metabolic syndrome is not fully
      elucidated. The present study aims to: a) investigate the independent association
      of fitness on the prevalence of CAC, after adjustment for moderate-to-vigorous
      physical activity and sedentary time, and b) study the possible attenuation of
      increased CAC by higher fitness, in participants with metabolic syndrome. Design
      Cross-sectional. Methods In total 678 participants (52% women), 50-65 years old,
      from the SCAPIS pilot study were included. Fitness (VO2max) was estimated by
      submaximal cycle ergometer test and moderate-to-vigorous physical activity and
      sedentary time were assessed using hip-worn accelerometers. CAC score (CACS) was
      quantified using the Agatston score. Results The odds of having a significant
      CACS (>=100) was half in participants with moderate/high fitness compared with
      their low fitness counterparts. Further consideration of moderate-to-vigorous
      physical activity, sedentary time and number of components of the metabolic
      syndrome did only slightly alter the effect size. Those with metabolic syndrome
      had 47% higher odds for significant CAC compared with those without metabolic
      syndrome. However, moderate/high fitness seems to partially attenuate this risk,
      as further joint analysis indicated an increased odds for having significant CAC
      only in the unfit metabolic syndrome participants. Conclusions Being fit is
      associated with a reduced risk of having significant CAC in individuals with
      metabolic syndrome. While still very much underutilized, fitness should be taken
      into consideration in everyday clinical risk prediction in addition to the
      traditional risk factors of the metabolic syndrome.

PMID- 29171774
TI  - Advances in treating psoriasis in the elderly with small molecule inhibitors.
AB  - INTRODUCTION: Due to the chronic nature of psoriasis, the population of elderly
      psoriasis patients is increasing. However, many elderly psoriatic patients are
      not adequately treated because management is challenging as a result of
      comorbidities, polypharmacy, and progressive impairment of organ systems.
      Physicians may hesitate to use systemic or biologic agents in elderly psoriasis
      patients because of an increased risk of adverse events in this patient
      population. Small molecule medications are emerging as promising options for
      elderly patients with psoriasis and other inflammatory conditions. Areas covered:
      Here we review the efficacy, safety and tolerability of small molecule inhibitors
      apremilast, tofacitinib, ruxolitinib, baricitinib, and peficitinib in the
      treatment of psoriasis, with focus on their use in the elderly population. Expert
      opinion: Although small molecule inhibitors demonstrate efficacy in elderly
      patients with psoriasis, they will require larger head-to-head studies and post
      marketing registries to evaluate their effectiveness and safety in specific
      patient populations. Apremilast, ruxolitinib, and peficitinib are effective
      agents with favorable side effect profiles; however, physicians should exercise
      caution when prescribing tofacitinib or baricitinib in elderly populations due to
      adverse events. The high cost of these drugs in the U.S. is likely to limit their
      use.

PMID- 29171775
TI  - Acute high-fat feeding leads to disruptions in glucose homeostasis and worsens
      stroke outcome.
AB  - Chronic consumption of diets high in fat leads to obesity and can negatively
      affect brain function. Rodents made obese by long-term maintenance on a high-fat
      diet have worse outcome after experimental stroke. High-fat consumption for only
      three days does not induce obesity but has rapid effects on the brain including
      memory impairment. However, the effect of brief periods of high-fat feeding or
      high-fat consumption in the absence of obesity on stroke is unknown. We therefore
      tested the effect of an acute period of high-fat feeding (three days) in C57B/6
      mice on outcome after middle cerebral artery occlusion (MCAo). In contrast to a
      chronic high-fat diet (7.5 months), an acute high-fat diet had no effect on body
      weight, adipose tissue, lipid profile or inflammatory markers (in periphery and
      the brain). Three days of high-fat feeding impaired glucose tolerance, increased
      plasma glucose and insulin and brain expression of the glucose transporter GLUT
      1. Ischaemic damage was increased (48%) in mice fed an acute high-fat diet, and
      was associated with a further reduction in GLUT-1 in the ischaemic hemisphere.
      These data demonstrate that only a brief period of high-fat consumption has a
      negative effect on glucose homeostasis and worsens outcome after ischaemic
      stroke.

PMID- 29171777
TI  - The Annual IMI Awards 2017.

PMID- 29171776
TI  - Extended thromboprophylaxis in the acutely ill medical patient after
      hospitalization - a paradigm shift in post-discharge thromboprophylaxis.
AB  - Venous thromboembolism (VTE) is a significant healthcare burden with
      approximately 900,000 events annually in the United States, over half of which
      are healthcare-associated. This number is anticipated to double by 2050. Group
      prophylaxis strategies confined to the inpatient setting appear to have minimal
      impact on the reduction of post-discharge VTE in medically ill patients due to
      shortened lengths of stay and a heterogenous population that includes patients at
      low risk for VTE. In accordance with current guideline recommendations, very few
      (<5%) medically ill patients are discharged with extended prophylaxis, which
      potentially creates a clinical gap for at-risk patients as VTE risk has been
      shown to persist for up to 90 days. Initial studies of extended
      thromboprophylaxis in acutely ill medical patients with enoxaparin, rivaroxaban
      and apixaban showed little to no benefit towards VTE reduction that was
      consistently outweighed by increased bleeding. The more recent APEX study that
      compared betrixaban to enoxaparin in an enriched patient population at high-risk
      for VTE was the first study of extended thromboprophylaxis that showed similar
      efficacy in VTE prevention without an increase in major bleeding. Based on the
      APEX results, betrixaban recently gained FDA approval for extended
      thromboprophylaxis in acutely ill medical patients. Recognition that up to half
      of medically ill patients are not at sufficient risk to warrant
      thromboprophylaxis has driven extensive research towards development of
      scientifically derived and validated VTE risk assessment models intended to
      identify patients who do not warrant prophylaxis, as well as those at high risk
      who may derive benefit from extended thromboprophylaxis. This article will review
      prior and ongoing extended thromboprophylaxis studies, VTE and bleed risk
      assessment models, incorporation of biomarkers in VTE risk assessment and key
      issues in the paradigm shift towards individualized VTE prophylaxis in acutely
      ill medical patients.

PMID- 29171778
TI  - Effect of matrix composition, sphere size and hormone concentration on diffusion
      coefficient of insulin for controlled gastrointestinal delivery for diabetes
      treatment.
AB  - Oral insulin administration is limited due to its degradation by proteases. The
      hormone was encapsulated in spheres made of either pure calcium alginate (ALG) or
      its association with whey protein isolate (WPI-ALG) in order to minimise loss in
      the stomach region while allowing liberation in the maximum absorption area,
      located in the intestine. Diffusion coefficients for both matrix compositions
      were determined in vitro for gastric pH (5.88 and 10.26 * 10-12 m2 s-1) and
      intestinal pH (21.11 and 79.29 * 10-12 m2 s-1). Higher initial insulin
      concentrations and lower diameters accelerated its release, confirming Fickian
      behaviour. The analytic model exhibited a good fit in most cases. Computer
      simulations revealed that ALG spheres are more convenient for oral administration
      because they release more insulin in the intestine than the WPI-ALG ones, thus
      supporting its therapeutic viability for the purpose of reducing stress in those
      who depend on insulin.

PMID- 29171779
TI  - Five-year forward view: lessons from emergency care at the extremes of age.
AB  - Objective The progressive rise in demand on NHS emergency care resources is
      partly attributable to increases in attendances of children and older people. A
      quality gap exists in the care provision for the old and the young. The Five Year
      Forward View suggested new models of care but that the "answer is not one-size
      fits-all". This article discusses the urgent need for person-centred outcome
      measures to bridge the gap that exists between demand and provision. Design This
      review is based on evidence gathered from literature searching across several
      platforms using a variety of search terms to account for the obvious
      heterogeneity, drawing on key 'think-tank' evidence. Settings Qualitative and
      quantitative studies examining approaches to caring for individuals at the
      extremes of age. Participants Individuals at the extremes of age (infants and
      older people). Main Outcome Measures Understanding similarities and disparities
      in the care of individuals at the extremes of age in an emergency and non
      emergency context. Results There exists several similarities and disparities in
      the care of individuals at the extremes of age. The increasing burden of health
      disease on the economy must acknowledge the challenges that exist in managing
      patients in emergency settings at the extremes of age and build systems to
      acknowledge the traits these individuals exhibit. Conclusion Commissioners of
      services must optimise the models of care delivery by appreciating the
      similarities and differences between care requirements in these two large groups
      seeking emergency care.

PMID- 29171780
TI  - Did Winston Churchill suffer a myocardial infarction in the White House at
      Christmas 1941?
AB  - While staying in the White House over Christmas 1941, Churchill developed chest
      pain on trying to open a window in his bedroom. Sir Charles Wilson, his personal
      physician, diagnosed a 'heart attack' (myocardial infarction). Wilson, for
      political and personal reasons, decided not to inform his patient of the
      diagnosis or obtain assistance from US medical colleagues. On Churchill's return
      to London, Wilson sought a second opinion from Dr John Parkinson who did not
      support the diagnosis of coronary thrombosis (myocardial infarction) and
      reassured Churchill accordingly.

PMID- 29171781
TI  - Training for population and personalised healthcare.

PMID- 29171782
TI  - Politics, scapegoating and mass psychogenic illness: claims of an 'acoustical
      attack' in Cuba are unsound.

PMID- 29171783
TI  - Hyperhomocysteinemia-induced autophagy and apoptosis with downregulation of hairy
      enhancer of split 1/5 in cortical neurons in mice.
AB  - It has been reported that hyperhomocysteinemia (HHcy) is associated with
      neurodegenerative and cardiovascular diseases. However, little is known about
      brain histomorphology, neuronal organelles, and hairy enhancer of split ( hes)
      expression under HHcy. In this study, non-HHcy and HHcy induced by high
      methionine diet in apolipoprotein E-deficient (Apo E-/-) mice were comparatively
      investigated. The histomorphology, ultrastructure, autophagosomes, apoptosis, and
      expression of proteins, HES1, HES5 and P62, were designed to assess the effects
      of HHcy on brain. The results showed that compared to the non-HHcy mice, the HHcy
      group had an increase in autophagosomes, vacuolization in mitochondria, and
      neuron apoptosis; treatment with folate and vitamin B12 reduced the extent of
      these lesions. However, the elementary histomorphology, the numbers of cortical
      neurons, and Nissl bodies had no significant difference between the HHcy and the
      non-HHcy groups or the group treated with folate and vitamin B12.
      Immunohistochemistry and immunofluorescence demonstrated a decrease in HES1- or
      HES5-positive neurons in the HHcy group when compared to the non-HHcy groups,
      wild-type, and Apo E-/- controls, or the HHcy mice with folate and vitamin B12
      supplement. Western blots showed that HHcy induced a decreased expression of HES1
      and HES5, or P62, in which the expression of HES1 and P62 was elevated by
      treating with folate and vitamin B12 supplement. These results suggest that HHcy
      enhanced brain damage is associated with increased autophagy and neuronal
      apoptosis in Apo E-/- mice, in which downregulation of hes1 and hes5 is involved.

PMID- 29171784
TI  - Necroptosis promotes autophagy-dependent upregulation of DAMP and results in
      immunosurveillance.
AB  - Programmed necrosis, necroptosis, is considered to be a highly immunogenic
      activity, often mediated via the release of damage-associated molecular patterns
      (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often
      found to be accompanied by necroptosis. However, the possible role of autophagy
      in the immunogenicity of necroptotic death remains largely obscure. In this
      study, we investigated the possible mechanistic correlation between phytochemical
      shikonin-induced autophagy and the shikonin-induced necroptosis for tumor
      immunogenicity. We show that shikonin can instigate RIPK1 (receptor [TNFRSF]
      interacting serine-threonine kinase 1)- and RIPK3 (receptor-interacting serine
      threonine kinase 3)-dependent necroptosis that is accompanied by enhanced
      autophagy. Shikonin-induced autophagy can directly contribute to DAMP
      upregulation. Counterintuitively, among the released and ectoDAMPs, only the
      latter were shown to be able to activate the cocultured dendritic cells (DCs).
      Interruption of autophagic flux via chloroquine further upregulated ectoDAMP
      activity and resultant DC activation. For potential clinical application, DC
      vaccine preparations treated with tumor cells that were already pretreated with
      chloroquine and shikonin further enhanced the antimetastatic activity of 4T1
      tumors and reduced the effective dosage of doxorubicin. The enhanced
      immunogenicity and vaccine efficacy obtained via shikonin and chloroquine
      cotreatment of tumor cells may thus constitute a compelling strategy for
      developing cancer vaccines via the use of a combinational drug treatment.

PMID- 29171786
TI  - Bidirectional Regulation of Genistein on the Proliferation and Differentiation of
      C2C12 Myoblasts.
AB  - 1. Genistein is a widely studied phytoestrogen. The effects of genistein on
      myoblasts were reported long ago, but the conclusions are controversial. In the
      current study, we evaluated the effects of different concentrations of genistein
      on C2C12 myoblasts. 2. Genistein treatment promoted myoblast proliferation in a
      dose-development manner in the 0-2 uM/L range, reaching its maximum effect at 2
      uM/L. Proliferation then declined, and a concentration higher than 20 uM/L showed
      significant inhibition. Additionally, genistein treatment promoted myoblast
      differentiation at a dose of 10 uM/L. However, at treatment concentrations higher
      than 10 uM/L, the effect on myoblast differentiation was rapidly inhibited as the
      concentration increased. 3. Genistein treatment also downregulated miR-222,
      resulting in increased expression of its target genes, MyoG, MyoD and ERalpha and
      thereby promoting myoblast differentiation. 4. Our results suggest that genistein
      has a dose-dependent and bidirectional regulation effect on myoblast
      proliferation and differentiation. We also found that genistein is a miRNA
      inducer, and it specifically affects the expression of miR-222 to regulate
      myoblast differentiation.

PMID- 29171787
TI  - Effectiveness and usability of Scanning Wizard software: a tool for enhancing
      switch scanning.
AB  - Scanning Wizard software helps scanning users improve the setup of their switch
      and scanning system. This study evaluated Scanning Wizard's effectiveness and
      usability. Ten people who use switch scanning and ten practitioners used Scanning
      Wizard in the initial session. Usability was high, based on survey responses
      averaging over 4.5 out of 5, and qualitative feedback was very positive. Five
      switch users were able to complete the multi-week protocol, using settings on
      their own scanning system that were recommended from the Scanning Wizard session.
      Using these revised settings, text entry rates improved by an average of 71%,
      ranging from 29% to 172% improvement. Results suggest that Scanning Wizard is a
      useful tool for improving the configuration of scanning systems for people who
      use switch scanning to communicate. Implications for Rehabilitation Some
      individuals with severe physical impairments use switch scanning for spoken and
      written communication. Scanning Wizard software helps scanning users improve the
      setup of their switch and scanning system. This study demonstrated high usability
      of Scanning Wizard (with 10 switch userpractitioner teams) and increased text
      entry rate by an average of 71% (for five switch users). Results suggest that
      Scanning Wizard is a useful tool for improving the configuration of scanning
      systems for people who use switch scanning to communicate.

PMID- 29171785
TI  - Regulation of RNA polymerase III transcription during transformation of human
      IMR90 fibroblasts with defined genetic elements.
AB  - RNA polymerase (Pol) III transcribes small untranslated RNAs that are essential
      for cellular homeostasis and growth. Its activity is regulated by inactivation of
      tumor suppressor proteins and overexpression of the oncogene c-MYC, but the
      concerted action of these tumor-promoting factors on Pol III transcription has
      not yet been assessed. In order to comprehensively analyse the regulation of Pol
      III transcription during tumorigenesis we employ a model system that relies on
      the expression of five genetic elements to achieve cellular transformation.
      Expression of these elements in six distinct transformation intermediate cell
      lines leads to the inactivation of TP53, RB1, and protein phosphatase 2A, as well
      as the activation of RAS and the protection of telomeres by TERT, thereby
      conducting to full tumoral transformation of IMR90 fibroblasts. Transformation is
      accompanied by moderately enhanced levels of a subset of Pol III-transcribed RNAs
      (7SK; MRP; H1). In addition, mRNA and/or protein levels of several Pol III
      subunits and transcription factors are upregulated, including increased protein
      levels of TFIIIB and TFIIIC subunits, of SNAPC1 and of Pol III subunits.
      Strikingly, the expression of POLR3G and of SNAPC1 is strongly enhanced during
      transformation in this cellular transformation model. Collectively, our data
      indicate that increased expression of several components of the Pol III
      transcription system accompanied by a 2-fold increase in steady state levels of a
      subset of Pol III RNAs is sufficient for sustaining tumor formation.

PMID- 29171788
TI  - Endovascular retrieval of a migrating pedicle screw within the inferior vena cava
      after instrumented spinal surgery: case report.
AB  - During L3-5 instrumented spinal surgery for degenerative spondylolisthesis in a
      75-year-old woman, the right L-3 pedicle screw was accidentally pushed into the
      retroperitoneum and then migrated to the inferior vena cava (IVC). The patient
      was transferred to the surgical intensive care unit, and after careful discussion
      with cardiology specialists, a minimally invasive endovascular technique was used
      to remove the migrating pedicle screw within the IVC and thus salvage this
      critical case. Pedicle screw instrumentation is an effective procedure, but not
      risk free. Every detail should be scrutinized during surgery, even instrument
      construction. A minimally invasive endovascular technique should be considered in
      this patient population.

PMID- 29171789
TI  - Accuracy of identification of low or high risk lifting during standardised
      lifting situations.
AB  - The aim was to classify lifting activities into low and high risk categories
      (according to The Danish Working Environment Authority guidelines) based on
      surface electromyography (sEMG) and trunk inclination (tri-axial accelerometer)
      measurements. Lifting tasks with different weights, horizontal distance and
      technique were performed. The lifting tasks were characterised by a feature
      vector composed of either the 90th, 95th or 99th percentile of sEMG activity
      level and trunk inclinations during the task. Linear Discriminant Analysis and a
      subject-specific threshold scheme were applied and lifting tasks were classified
      with an accuracy of 65.1-65.5%. When lifts were classified based on the subject
      specific threshold scheme from low and upper back accelerometers, the accuracy
      reached 52.1-58.1% and 72.7-78.1%, respectively. In conclusion, the use of
      subject-specific thresholds from sEMG from upper trapezius and erector spinae as
      well as inclination of the upper trunk enabled us to identify low and high risk
      lifts with an acceptable accuracy. Practitioner Summary: This study contributes
      to the development of a method enabling the automatic detection of high risk
      lifting tasks, i.e. exposure to high biomechanical loads, based on individual
      sEMG and kinematics from an entire working day. These methods may be more cost
      effective and may complement observations commonly used by practitioners.

PMID- 29171790
TI  - Transcriptomic Analysis of Arabidopsis Seedlings in Response to an Agrobacterium
      Mediated Transformation Process.
AB  - Agrobacterium tumefaciens is a plant pathogen that causes crown gall disease.
      This pathogen is capable of transferring the T-DNA from its Ti plasmid to the
      host cell and, then, integrating it into the host genome. To date, this genetic
      transformation ability has been harnessed as the dominant technology to produce
      genetically modified plants for both basic research and crop biotechnological
      applications. However, little is known about the interaction between
      Agrobacterium tumefaciens and host plants, especially the host responses to
      Agrobacterium infection and its associated factors. We employed RNA-seq to follow
      the time course of gene expression in Arabidopsis seedlings infected with either
      an avirulent or a virulent Agrobacterium strain. Gene Ontology analysis indicated
      many biological processes were involved in the Agrobacterium-mediated
      transformation process, including hormone signaling, defense response, cellular
      biosynthesis, and nucleic acid metabolism. RNAseq and quantitative reverse
      transcription-polymerase chain reaction results indicated that expression of
      genes involved in host plant growth and development were repressed but those
      involved in defense response were induced by Agrobacterium tumefaciens. Further
      analysis of the responses of transgenic Arabidopsis lines constitutively
      expressing either the VirE2 or VirE3 protein suggested Vir proteins act to
      enhance plant defense responses in addition to their known roles facilitating T
      DNA transformation.

PMID- 29171791
TI  - Voice and swallowing outcomes following reoperative anterior cervical discectomy
      and fusion with a 2-team surgical approach.
AB  - OBJECTIVE Dysphagia and vocal cord palsy (VCP) are common complications after
      anterior cervical discectomy and fusion (ACDF). The reported incidence rates for
      dysphagia and VCP are variable. When videolaryngostroboscopy (VLS) is performed
      to assess vocal cord function after ACDF procedures, the incidence of VCP is
      reported to be as high as 22%. The incidence of dysphagia ranges widely, with
      estimates up to 71%. However, to the authors' knowledge, there are no prospective
      studies that demonstrate the rates of VCP and dysphagia for reoperative ACDF.
      This study aimed to investigate the incidence of voice and swallowing
      disturbances before and after reoperative ACDF using a 2-team operative approach
      with comprehensive pre- and postoperative assessment of swallowing, direct vocal
      cord visualization, and clinical neurosurgical outcomes. METHODS A convenience
      sample of sequential patients who were identified as requiring reoperative ACDF
      by the senior spinal neurosurgeon at the University of Alabama at Birmingham were
      enrolled in a prospective, nonrandomized study during the period from May 2010
      until July 2014. Sixty-seven patients undergoing revision ACDF were enrolled
      using a 2-team approach with neurosurgery and otolaryngology. Dysphagia was
      assessed both preoperatively and postoperatively using the MD Anderson Dysphagia
      Inventory (MDADI) and fiberoptic endoscopic evaluation of swallowing (FEES),
      whereas VCP was assessed using direct visualization with VLS. RESULTS Five
      patients (7.5%) developed a new postoperative temporary VCP after reoperative
      ACDF. All of these cases resolved by 2 months postoperatively. There were no new
      instances of permanent VCP. Twenty-five patients had a new swallowing disturbance
      detected on FEES compared with their baseline assessment, with most being mild
      and requiring no intervention. Nearly 60% of patients showed a decrease in their
      postoperative MDADI scores, particularly within the physical subset. CONCLUSIONS
      A 2-team approach to reoperative ACDF was safe and effective, with no new cases
      of VCP on postoperative VLS. Dysphagia rates as assessed through the MDADI scale
      and FEES were consistent with other published reports.

PMID- 29171792
TI  - Preparation and characteristics of the sulfonated chitosan derivatives
      electrodeposited onto 316l stainless steel surface.
AB  - In order to ameliorate the properties of corrosion resistance and achieve
      applications in anti-biofouling of 316L stainless steel (SS), a sulfated
      derivative of chitosan was deposited onto stainless steel surface by an
      electrochemical method. In detail, chitosan-catechol (CS-CT) was synthesised in
      the hydrochloric acid solution by the Mannich reaction and then electrodeposited
      on the surface of the polished 316L stainless steel. The chitosan-catechol
      deposited SS sample was further modified with maleic anhydride and sulfite. The
      grafting progress was monitored by FTIR, UV spectrophotometer and X-ray
      photoelectron spectroscopy. Hydrophilicity and corrosion resistance of modified
      SS were characterized by water contact angle measurements, Tafel curves and
      electrochemical impedance spectroscopy. The morphology of the SS surface before
      and after the modification was investigated by atomic force microscopy and
      scanning electron microscope. Further, the anti-biofouling performance in terms
      of the anti-adsorption protein and anti-bacteria effects of all modified SS
      samples were estimated, and the modified 316L exhibits the capability of lower
      protein adsorption and improved antibacterial effect.

PMID- 29171793
TI  - Preoperative skin antisepsis with chlorhexidine gluconate versus povidone-iodine:
      a prospective analysis of 6959 consecutive spinal surgery patients.
AB  - OBJECTIVE The aim of this study was to determine the efficacy of 2 common
      preoperative surgical skin antiseptic agents, ChloraPrep and Betadine, in the
      reduction of postoperative surgical site infection (SSI) in spinal surgery
      procedures. METHODS Two preoperative surgical skin antiseptic agents-ChloraPrep
      (2% chlorhexidine gluconate and 70% isopropyl alcohol) and Betadine (7.5%
      povidone-iodine solution)-were prospectively compared across 2 consecutive time
      periods for all consecutive adult neurosurgical spine patients. The primary end
      point was the incidence of SSI. RESULTS A total of 6959 consecutive spinal
      surgery patients were identified from July 1, 2011, through August 31, 2015, with
      4495 (64.6%) and 2464 (35.4%) patients treated at facilities 1 and 2,
      respectively. Sixty-nine (0.992%) SSIs were observed. There was no significant
      difference in the incidence of infection between patients prepared with Betadine
      (33 [1.036%] of 3185) and those prepared with ChloraPrep (36 [0.954%] of 3774; p
      = 0.728). Neither was there a significant difference in the incidence of
      infection in the patients treated at facility 1 (52 [1.157%] of 4495) versus
      facility 2 (17 [0.690%] of 2464; p = 0.06). Among the patients with SSI, the most
      common indication was degenerative disease (48 [69.6%] of 69). Fifty-one (74%)
      patients with SSI had undergone instrumented fusions in the index operation, and
      38 (55%) patients with SSI had undergone revision surgeries. The incidence of SSI
      for minimally invasive and open surgery was 0.226% (2 of 885 cases) and 1.103%
      (67 of 6074 cases), respectively. CONCLUSIONS The choice of either ChloraPrep or
      Betadine for preoperative skin antisepsis in spinal surgery had no significant
      impact on the incidence of postoperative SSI.

PMID- 29171794
TI  - Nutrient removal from synthetic and secondary treated sewage and tannery
      wastewater through phycoremediation.
AB  - In this study, potential microalgae species (Chlorella vulgaris, Scenedesmus
      dimorphus, Chlorococcum sp. and Chlamydomonas sp.) have been studied for nutrient
      removal from synthetic and industrial wastewater. Batch experiments were carried
      out to investigate the removal performance among four chosen species at different
      nitrogen and phosphorus concentrations. NH4-N and PO4-P were varied from 13.2 to
      52.8 mg/L and 6.6 to 26.4 mg/L, respectively, by keeping N:P ratio as 2:1. In
      synthetic wastewater, maximum NH4-N and PO4-P removal efficiencies of 88.6% and
      91.2% were obtained with C. vulgaris when compared to the other microalgae
      studied. Further studies were carried out using C. vulgaris in batch experiments
      to investigate the nutrient removal performance in secondary treated sewage, soak
      liquor and composite tannery effluent. Experimental results indicated that NH4-N,
      NO3-N, PO4-P and chemical oxygen demand (COD) removal efficiencies were found to
      be 68.6%, 74%, 71.5% and 90.2%, respectively, in secondary treated sewage.
      Maximum removal efficiencies of NH4-N, NO3-N, PO4-P and COD in composite tannery
      wastewater were found to be 55%, 85.6%, 60.5% and 43.4%, respectively. In soak
      liquor, maximum removal efficiencies of NH4-N, NO3-N, PO4-P and COD were found to
      66.7%, 62.6%, 63.6% and 93.8%, respectively.

PMID- 29171795
TI  - Young men's rationales for non-exclusive gay sexualities.
AB  - Recent evidence suggests it is useful to distinguish sexual identities among
      young men at the gay end of the spectrum because of group differences between
      primarily gay, mostly gay and gay orientations on several assessed physiological,
      behavioural and self-report measures. However, little is known about individuals'
      rationales for choosing sexuality labels beyond traditional gay or bisexual
      categories. We addressed this issue by interviewing 24 young men with a non
      exclusive gay orientation about their sexual desires and histories, drawing on
      both qualitative and numeric data. Undertaking an inductive analysis, we found
      four distinct rationales for identification with a sexual orientation label:
      sexual, romantic, intellectual and internalised homophobia. By examining what
      young men mean when they classify themselves as primarily gay, mostly gay or
      bisexual-leaning gay, this article provides data to understand these issues and
      proposes that greater focus should be placed on sexual identity for non-exclusive
      gay men. Although the sexual and affectional components of sexual orientation are
      meaningful, previous research has not sufficiently accounted for the importance
      of intellectual, cultural and romantic factors in non-exclusive sexual
      orientations. To address these issues, the use of in-depth interviews should be
      incorporated in future studies.

PMID- 29171796
TI  - 'He's not my pimp': toward an understanding of intimate male partner involvement
      in female sex work at the Mexico-US border.
AB  - Female sex work is often perceived as women being controlled by men. We used
      surveys and qualitative interviews with female sex workers and their intimate
      partners in two Northern Mexico cities to examine couples' own perceptions of
      their relationships and male partners' involvement in sex work. Among 214
      couples, the median age was 34 and relationship duration was approximately 3
      years. Only 10 women in the survey reported having a pimp, and the majority
      reported sole control over sex work decisions. Qualitative analyses revealed that
      while most men avoided direct involvement in sex work, they offered advice that
      was largely driven by concern for their partner's well-being. Our discussion of
      these results considers the broader socio-political context surrounding these
      relationships and how changing gender roles, economic insecurity and stigma shape
      couples' everyday social interactions. Assumptions that all sex workers'
      relationships are coercive and commercial marginalises these couples while
      leaving their health concerns unaddressed.

PMID- 29171797
TI  - Health-related quality of life outcomes in complex adult spinal deformity
      surgery.
AB  - OBJECTIVE Significant health-related quality of life (HRQOL) benefits have been
      observed for patients undergoing primary and revision adult spinal deformity
      (ASD) surgery. The purpose of this study was to report changes in HRQOL measures
      in a consecutive series of patients undergoing complex spinal reconstructive
      surgery, using Scoli-RISK-1 (SR-1) inclusion criteria. METHODS This was a single
      center, retrospective cohort study. The SR-1 inclusion criteria were used to
      define patients with complex ASD treated between June 1, 2009, and June 1, 2011.
      Standard preoperative and perioperative data were collected, including the
      Scoliosis Research Society (SRS)-22r instrument. The HRQOL changes were evaluated
      at a minimum 2-year follow-up. Standardized forms were used to collect surgery
      related complications data for all patients. Complications were defined as minor,
      transient major, or permanent major. Patients who achieved a minimum 2-year
      follow-up were included in the analysis. RESULTS Eighty-four patients meeting SR
      1 criteria were identified. Baseline demographic and surgical data were available
      for 74/84 (88%) patients. Forty-seven of 74 (64%) patients met the additional
      HRQOL criteria with a minimum 2-year follow-up (mean follow-up 3.4 years, range 2
      6.5 years). Twenty-one percent of patients underwent posterior fusion only, 40%
      of patients had a posterior column osteotomy, and 38% had a 3-column osteotomy.
      Seventy-five percent of patients underwent a revision procedure. Significant
      improvements were observed in all SRS-22r domains: Pain: +0.8 (p < 0.001); Self
      Image: +1.4 (p < 0.001); Function: +0.46 (p < 0.001); Satisfaction: +1.6 (p <
      0.001); and Mental Health: +0.28 (p = 0.04). With the exception of Mental Health,
      more than 50% of patients achieved a minimum clinically important difference
      (MCID) in SRS-22r domain scores (Mental Health: 20/47, 42.6%). A total of 65
      complications occurred in 31 patients. This includes 29.8% (14/47) of patients
      who suffered a major complication and 17% (8/47) who suffered a postoperative
      neurological deficit, most commonly at the root level (10.6%, 5/47). Of the 8
      patients who suffered a neurological deficit, 1 (13%) was able to achieve MCID in
      the SRS Function domain. CONCLUSIONS The majority of patients experienced
      clinically relevant improvement in SRS-22r HRQOL scores after complex ASD
      surgery. The greatest improvements were seen in the SRS Pain and SRS Self-Image
      domains. Although 30% of patients suffered a major or permanent complication,
      benefits from surgery were still attained. Patients sustaining a neurological
      deficit or major complication were unlikely to achieve HRQOL improvements meeting
      or exceeding MCID for the SRS Function domain.

PMID- 29171798
TI  - Orbital lymphatic-venous malformation with concomitant spontaneous orbital
      arteriovenous fistula: case report.
AB  - The authors describe the case of an 11-year-old boy with no history of prior
      trauma, who experienced acute proptosis and visual loss while showering.
      Diagnostic carotid artery angiography revealed an orbital lymphatic-venous
      malformation (LVM) concomitant with an intraorbital arteriovenous fistula. The
      patient was treated with transvenous coil and N-butyl cyanoacrylate glue
      embolization, combined with direct percutaneous glue injection into the LVM
      followed by excision. There was good clinical and radiological response without
      recurrence at the 2-year follow-up. Diagnostic carotid angiography should be
      considered in cases of orbital LVM, as a concomitant arteriovenous fistula might
      be present in rare cases.

PMID- 29171799
TI  - Surgical management of cerebellopontine angle arachnoid cysts associated with
      hearing deficit in pediatric patients.
AB  - OBJECTIVE Few cases of cerebellopontine angle (CPA) arachnoid cysts in pediatric
      patients have been described in the literature, and in only 2 of these cases were
      the patients described as suffering from hearing deficit. In this article, the
      authors report on 3 pediatric patients with CPA arachnoid cysts (2 with hearing
      loss and 1 with recurrent headaches) who underwent neurosurgical treatment at the
      authors' institution. METHODS Four pediatric patients were diagnosed with CPA
      arachnoid cysts at the International Neuroscience Institute during the period
      from October 2004 through August 2012, and 3 of these patients underwent surgical
      treatment. The authors describe the patients' clinical symptoms, the surgical
      approach, and the results on long-term follow-up. RESULTS One patient (age 14
      years) who presented with headache (without hearing deficit) became asymptomatic
      after surgical treatment. The other 2 patients who underwent surgical treatment
      both had hearing loss. One of these children (age 9 years) had recent-onset
      hypacusia and experienced complete recovery immediately after the surgery. The
      other (age 6 years) had a longer history (2 years) of progressive hearing loss
      and showed an interruption of the deficit progression and only mild improvement
      at the follow-up visit. CONCLUSIONS CPA arachnoid cysts are uncommon in pediatric
      patients. The indication and timing of the surgical treatment are fundamental,
      especially when a hearing deficit is present.

PMID- 29171800
TI  - Chiari-related scoliosis: a single-center experience with long-term radiographic
      follow-up and relationship to deformity correction.
AB  - OBJECTIVE Previous reports have addressed the short-term response of patients
      with Chiari-related scoliosis (CRS) to suboccipital decompression and duraplasty
      (SODD); however, the long-term behavior of the curve has not been well defined.
      The authors undertook a longitudinal study of a cohort of patients who underwent
      SODD for CRS to determine whether there are factors related to Chiari
      malformation (CM) that predict long-term scoliotic curve behavior and need for
      deformity correction. METHODS The authors retrospectively reviewed cases in which
      patients underwent SODD for CRS during a 14-year period at a single center.
      Clinical (age, sex, and associated disorders/syndromes) and radiographic (CM
      type, tonsillar descent, pBC2 line, clival-axial angle [CXA], syrinx length and
      level, and initial Cobb angle) information was evaluated to identify associations
      with the primary outcome: delayed thoracolumbar fusion for progressive scoliosis.
      RESULTS Twenty-eight patients were identified, but 4 were lost to follow-up and 1
      underwent fusion within a year. Among the remaining 23 patients, 11 required
      fusion surgery at an average of 88.3 +/- 15.4 months after SODD, including 7
      (30%) who needed fusion more than 5 years after SODD. On univariate analysis, a
      lower CXA (131.5 degrees  +/- 4.8 degrees  vs 146.5 degrees  +/- 4.6 degrees , p
      = 0.034), pBC2 > 9 mm (64% vs 25%, p = 0.06), and higher initial Cobb angle (35.1
      degrees  +/- 3.6 degrees  vs 22.8 degrees  +/- 4.0 degrees , p = 0.035) were
      associated with the need for thoracolumbar fusion. Multivariable modeling
      revealed that lower CXA was independently associated with a need for delayed
      thoracolumbar fusion (OR 1.12, p = 0.0128). CONCLUSIONS This investigation
      demonstrates the long-term outcome and natural history of CRS after SODD. The
      durability of the effect of SODD on CRS and curve behavior is poor, with late
      curve progression occurring in 30% of patients. Factors associated with CRS
      progression include an initial pBC2 > 9 mm, lower CXA, and higher Cobb angle.
      Lower CXA was an independent predictor of delayed thoracolumbar fusion. Further
      study is necessary on a larger cohort of patients to fully elucidate this
      relationship.

PMID- 29171801
TI  - Intraoperative and postoperative complications in the surgical treatment of
      craniosynostosis: minimally invasive versus open surgical procedures.
AB  - OBJECTIVE To compare minimally invasive endoscopic and open surgical procedures,
      to improve informed consent of parents, and to establish a baseline for further
      targeted improvement of surgical care, this study evaluated the complication rate
      and blood transfusion rate of craniosynostosis surgery in our department. METHODS
      A prospective complication registration database that contains a consecutive
      cohort of all pediatric neurosurgical procedures in the authors' neurosurgical
      department was used. All pediatric patients who underwent neurosurgical treatment
      for craniosynostosis between February 2004 and December 2014 were included. In
      total, 187 procedures were performed, of which 121 were endoscopically assisted
      minimally invasive procedures (65%). Ninety-three patients were diagnosed with
      scaphocephaly, 50 with trigonocephaly, 26 with plagiocephaly, 3 with
      brachycephaly, 9 with a craniosynostosis syndrome, and 6 patients were suffering
      from nonsyndromic multisutural craniosynostosis. RESULTS A total of 18
      complications occurred in 187 procedures (9.6%, 95% CI 6.2-15), of which 5.3% (n
      = 10, 95% CI 2.9-10) occurred intraoperatively and 4.2% (n = 8, 95% CI 2.2-8.2)
      occurred postoperatively. In the open surgical procedure group, 9 complications
      occurred: 6 intraoperatively and 3 postoperatively. In the endoscopically
      assisted procedure group, 9 complications occurred: 4 intraoperatively and 5
      postoperatively. Blood transfusion was needed in 100% (n = 66) of the open
      surgical procedures but in only 21% (n = 26, 95% CI 15-30) of the endoscopic
      procedures. One patient suffered a transfusion reaction, and 6 patients suffered
      infections, only one of which was a surgical site infection. A dural tear was the
      most common intraoperative complication that occurred (n = 8), but it never led
      to postoperative sequelae. Intraoperative bleeding from a sagittal sinus occurred
      in one patient with only minimal blood loss. There were no deaths, permanent
      morbidity, or neurological sequelae. CONCLUSIONS Complications during
      craniosynostosis surgery were relatively few and minor and were without permanent
      sequelae in open and in minimally invasive procedures. The blood transfusion rate
      was significantly reduced in endoscopic procedures compared with open procedures.

PMID- 29171803
TI  - Letter to the Editor. Puzzling posology: was the bevacizumab regimen in recurrent
      glioblastoma misreported?

PMID- 29171802
TI  - Is the chiasm-pituitary corridor size important for achieving gross-total
      resection during endonasal endoscopic resection of craniopharyngiomas?
AB  - OBJECTIVE Craniopharyngiomas arise from the pituitary stalk, and in adults they
      are generally located posterior to the chiasm extending up into the third
      ventricle. The extended endonasal approach (EEA) can provide an ideal corridor
      between the bottom of the optic chiasm and the top of the pituitary gland (chiasm
      pituitary corridor [CPC]) for their removal. A narrow CPC in patients with a
      prefixed chiasm and a large tumor extending up and behind the chiasm has been
      considered a contraindication to EEA, with a high risk of visual deterioration
      and subtotal resection. METHODS A database of all patients treated in the
      authors' center (Weill Cornell Medical College, NewYork-Presbyterian Hospital)
      between July 2004 and August 2016 was reviewed. Patients with craniopharyngiomas
      who underwent EEA with the goal of gross-total resection (GTR) were included in
      the study. Patients with postfixed chiasm or limited available preoperative
      imaging were excluded. Using preoperative contrast-enhanced T1-weighted sagittal
      midline MR images, the authors calculated the CPC as well as the distance from
      the chiasm to the top of the tumor (CTOT). From these numbers, they calculated a
      ratio of the CPC to the CTOT as a measure of difficulty in removing the tumors
      through the EEA and called this ratio the corridor index (CI). The relationship
      between the CI and the ability to achieve GTR and visual outcome were measured.
      RESULTS Thirty-four patients were included in the study. The mean CPC was 10.1 mm
      (range 5.2-19.1 mm). The mean CTOT was 12.8 mm (range 0-28.3 mm). The median CI
      was 0.8; the CI ranged from 0.4 to infinity (for tumors with a CTOT of 0). Thirty
      two patients had GTR (94.1%) and 2 had subtotal resection. The CPC value had no
      relationship with our ability to achieve GTR and no effect on visual or endocrine
      outcome. CONCLUSIONS EEA for craniopharyngioma is generally considered the first
      line surgical approach. Although a narrow corridor between the top of the
      pituitary gland and the bottom of the chiasm may seem to be a relative
      contraindication to surgery for larger tumors, the authors' data do not bear this
      out. EEA appears to be a successful technique for the majority of midline
      craniopharyngiomas.

PMID- 29171805
TI  - Erratum. Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series
      of 13 cases.

PMID- 29171804
TI  - An intraoperative motor tract positioning method in brain tumor surgery:
      technical note.
AB  - Intraoperative 3D recognition of the motor tract is indispensable to avoiding
      neural fiber injury in brain tumor surgery. However, precise localization of the
      tracts is sometimes difficult with conventional mapping methods. Thus, the
      authors developed a novel brain mapping method that enables the 3D recognition of
      the motor tract for intrinsic brain tumor surgeries. This technique was performed
      in 40 consecutive patients with gliomas adjacent to motor tracts that have a risk
      of intraoperative pyramidal tract damage. Motor tracts were electrically
      stimulated and identified by a handheld brain-mapping probe, the NY Tract Finder
      (NYTF). Sixteen-gauge plastic tubes were mounted onto the NYTF and inserted in
      the estimated direction of the motor tract with reference to navigational
      information. Only the NYTF was removed, leaving the plastic tubes in their
      places, immediately after muscle motor evoked potentials were recorded at the
      minimum stimulation current. Motor tracts were electrically identified in all
      cases. Three-dimensional information on the position of motor tracts was given by
      plastic tubes that were neurophysiologically placed. Tips of tubes showed the
      resection limit during tumor removal. Safe tumor resection with an arbitrary
      safety margin can be performed by adjusting the length of the plastic tubes. The
      motor tract positioning method enabled the 3D recognition of the motor tract by
      surgeons and provided for safe resection of tumors. Tumor resections were
      performed safely before damaging motor tracts, without any postoperative
      neurological deterioration.

PMID- 29171806
TI  - Letter to the Editor. Computed tomography angiography in brain death
      determination: is there justification for its use?

PMID- 29171807
TI  - The venous delay phenomenon in computed tomography angiography: a novel imaging
      outcome predictor for poor cerebral perfusion after severe aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVE: Diverse treatment results are observed in patients with poor-grade
      aneurysmal subarachnoid hemorrhage (aSAH). Significant initial perfusion
      compromise is thought to predict a worse treatment outcome, but this has scant
      support in the literature. In this cohort study, the authors correlate the
      treatment outcomes with a novel poor-outcome imaging predictor representing
      impaired cerebral perfusion on initial CT angiography (CTA). METHODS: The authors
      reviewed the treatment results of 148 patients with poor-grade aSAH treated at a
      single tertiary referral center between 2007 and 2016. Patients with the "venous
      delay" phenomenon on initial CTA were identified. The outcome assessments used
      the modified Rankin Scale (mRS) at the 3rd month after aSAH. Factors that may
      have had an impact on outcome were retrospectively analyzed. RESULTS: Compared
      with previously identified outcome predictors, the venous delay phenomenon on
      initial CTA was found to have the strongest correlation with posttreatment
      outcomes on both univariable (p < 0.0001) and multivariable analysis (OR 4.480,
      95% CI 1.565-12.826; p = 0.0052). Older age and a higher Hunt and Hess grade at
      presentation were other factors that were associated with poor outcome, defined
      as an mRS score of 3 to 6. CONCLUSIONS: The venous delay phenomenon on initial
      CTA can serve as an imaging predictor for worse functional outcome and may aid in
      decision making when treating patients with poor-grade aSAH.

PMID- 29171808
TI  - Letter to the Editor. Determining brain death using computed tomography
      angiography.

PMID- 29171809
TI  - Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control.

PMID- 29171810
TI  - An Unconscious Patient with a DNR Tattoo.

PMID- 29171811
TI  - Simulation of Growth Trajectories of Childhood Obesity into Adulthood.
AB  - BACKGROUND: Although the current obesity epidemic has been well documented in
      children and adults, less is known about long-term risks of adult obesity for a
      given child at his or her present age and weight. We developed a simulation model
      to estimate the risk of adult obesity at the age of 35 years for the current
      population of children in the United States. METHODS: We pooled height and weight
      data from five nationally representative longitudinal studies totaling 176,720
      observations from 41,567 children and adults. We simulated growth trajectories
      across the life course and adjusted for secular trends. We created 1000 virtual
      populations of 1 million children through the age of 19 years that were
      representative of the 2016 population of the United States and projected their
      trajectories in height and weight up to the age of 35 years. Severe obesity was
      defined as a body-mass index (BMI, the weight in kilograms divided by the square
      of the height in meters) of 35 or higher in adults and 120% or more of the 95th
      percentile in children. RESULTS: Given the current level of childhood obesity,
      the models predicted that a majority of today's children (57.3%; 95% uncertainly
      interval [UI], 55.2 to 60.0) will be obese at the age of 35 years, and roughly
      half of the projected prevalence will occur during childhood. Our simulations
      indicated that the relative risk of adult obesity increased with age and BMI,
      from 1.17 (95% UI, 1.09 to 1.29) for overweight 2-year-olds to 3.10 (95% UI, 2.43
      to 3.65) for 19-year-olds with severe obesity. For children with severe obesity,
      the chance they will no longer be obese at the age of 35 years fell from 21.0%
      (95% UI, 7.3 to 47.3) at the age of 2 years to 6.1% (95% UI, 2.1 to 9.9) at the
      age of 19 years. CONCLUSIONS: On the basis of our simulation models, childhood
      obesity and overweight will continue to be a major health problem in the United
      States. Early development of obesity predicted obesity in adulthood, especially
      for children who were severely obese. (Funded by the JPB Foundation and others.).

PMID- 29171812
TI  - CGRP - The Next Frontier for Migraine.

PMID- 29171813
TI  - Case 37-2017. A 36-Year-Old Man with Unintentional Opioid Overdose.

PMID- 29171814
TI  - Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

PMID- 29171815
TI  - Recent Developments in Radiotherapy.

PMID- 29171816
TI  - Zenker's Diverticulum.

PMID- 29171818
TI  - Fremanezumab for the Preventive Treatment of Chronic Migraine.
AB  - BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin
      gene-related peptide (CGRP), is being investigated as a preventive treatment for
      migraine. We compared two fremanezumab dose regimens with placebo for the
      prevention of chronic migraine. METHODS: In this phase 3 trial, we randomly
      assigned patients with chronic migraine (defined as headache of any duration or
      severity on >=15 days per month and migraine on >=8 days per month) in a 1:1:1
      ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and
      placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at
      weeks 4 and 8), or matching placebo. Both fremanezumab and placebo were
      administered by means of subcutaneous injection. The primary end point was the
      mean change from baseline in the average number of headache days (defined as days
      in which headache pain lasted >=4 consecutive hours and had a peak severity of at
      least a moderate level or days in which acute migraine-specific medication
      [triptans or ergots] was used to treat a headache of any severity or duration)
      per month during the 12 weeks after the first dose. RESULTS: Of 1130 patients
      enrolled, 376 were randomly assigned to fremanezumab quarterly, 379 to
      fremanezumab monthly, and 375 to placebo. The mean number of baseline headache
      days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The
      least-squares mean (+/-SE) reduction in the average number of headache days per
      month was 4.3+/-0.3 with fremanezumab quarterly, 4.6+/-0.3 with fremanezumab
      monthly, and 2.5+/-0.3 with placebo (P<0.001 for both comparisons with placebo).
      The percentage of patients with a reduction of at least 50% in the average number
      of headache days per month was 38% in the fremanezumab-quarterly group, 41% in
      the fremanezumab-monthly group, and 18% in the placebo group (P<0.001 for both
      comparisons with placebo). Abnormalities of hepatic function occurred in 5
      patients in each fremanezumab group (1%) and 3 patients in the placebo group
      (<1%). CONCLUSIONS: Fremanezumab as a preventive treatment for chronic migraine
      resulted in a lower frequency of headache than placebo in this 12-week trial.
      Injection-site reactions to the drug were common. The long-term durability and
      safety of fremanezumab require further study. (Funded by Teva Pharmaceuticals;
      ClinicalTrials.gov number, NCT02621931 .).

PMID- 29171819
TI  - My Real Patients.

PMID- 29171817
TI  - HIV Prevention Efforts and Incidence of HIV in Uganda.
AB  - BACKGROUND: To assess the effect of a combination strategy for prevention of
      human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed
      the association between the incidence of HIV and the scale-up of antiretroviral
      therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in
      population-level viral-load suppression and sexual behaviors were also examined.
      METHODS: Between 1999 and 2016, data were collected from 30 communities with the
      use of 12 surveys in the Rakai Community Cohort Study, an open, population-based
      cohort of persons 15 to 49 years of age. We assessed trends in the incidence of
      HIV on the basis of observed seroconversion data, participant-reported use of
      ART, participant-reported male circumcision, viral-load suppression, and sexual
      behaviors. RESULTS: In total, 33,937 study participants contributed 103,011
      person-visits. A total of 17,870 persons who were initially HIV-negative were
      followed for 94,427 person-years; among these persons, 931 seroconversions were
      observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72%
      among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV
      positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male
      circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The
      percentage of adolescents 15 to 19 years of age who reported never having
      initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in
      2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42%
      relative to the period before 2006 (i.e., before the scale-up of the combination
      strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases
      per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence
      interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence
      rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate
      ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS: In this longitudinal study, the
      incidence of HIV infection declined significantly with the scale-up of a
      combination strategy for HIV prevention, which provides empirical evidence that
      interventions for HIV prevention can have a population-level effect. However,
      additional efforts are needed to overcome disparities according to sex and to
      achieve greater reductions in the incidence of HIV infection. (Funded by the
      National Institute of Allergy and Infectious Diseases and others.).

PMID- 29171821
TI  - A Controlled Trial of Erenumab for Episodic Migraine.
AB  - BACKGROUND: We tested erenumab, a fully human monoclonal antibody that inhibits
      the calcitonin gene-related peptide receptor, for the prevention of episodic
      migraine. METHODS: We randomly assigned patients to receive a subcutaneous
      injection of either erenumab, at a dose of 70 mg or 140 mg, or placebo monthly
      for 6 months. The primary end point was the change from baseline to months 4
      through 6 in the mean number of migraine days per month. Secondary end points
      were a 50% or greater reduction in mean migraine days per month, change in the
      number of days of use of acute migraine-specific medication, and change in scores
      on the physical-impairment and everyday-activities domains of the Migraine
      Physical Function Impact Diary (scale transformed to 0 to 100, with higher scores
      representing greater migraine burden on functioning). RESULTS: A total of 955
      patients underwent randomization: 317 were assigned to the 70-mg erenumab group,
      319 to the 140-mg erenumab group, and 319 to the placebo group. The mean number
      of migraine days per month at baseline was 8.3 in the overall population; by
      months 4 through 6, the number of days was reduced by 3.2 in the 70-mg erenumab
      group and by 3.7 in the 140-mg erenumab group, as compared with 1.8 days in the
      placebo group (P<0.001 for each dose vs. placebo). A 50% or greater reduction in
      the mean number of migraine days per month was achieved for 43.3% of patients in
      the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as
      compared with 26.6% in the placebo group (P<0.001 for each dose vs. placebo), and
      the number of days of use of acute migraine-specific medication was reduced by
      1.1 days in the 70-mg erenumab group and by 1.6 days in the 140-mg erenumab
      group, as compared with 0.2 days in the placebo group (P<0.001 for each dose vs.
      placebo). Physical-impairment scores improved by 4.2 and 4.8 points in the 70-mg
      and 140-mg erenumab groups, respectively, as compared with 2.4 points in the
      placebo group (P<0.001 for each dose vs. placebo), and everyday-activities scores
      improved by 5.5 and 5.9 points in the 70-mg and 140-mg erenumab groups,
      respectively, as compared with 3.3 points in the placebo group (P<0.001 for each
      dose vs. placebo). The rates of adverse events were similar between erenumab and
      placebo. CONCLUSIONS: Erenumab administered subcutaneously at a monthly dose of
      70 mg or 140 mg significantly reduced migraine frequency, the effects of
      migraines on daily activities, and the use of acute migraine-specific medication
      over a period of 6 months. The long-term safety and durability of the effect of
      erenumab require further study. (Funded by Amgen and Novartis; STRIVE
      ClinicalTrials.gov number, NCT02456740 .).

PMID- 29171822
TI  - ECG-Induced Koebner Phenomenon.

PMID- 29171820
TI  - Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy.

PMID- 29171823
TI  - Liraglutide and Renal Outcomes in Type 2 Diabetes.

PMID- 29171825
TI  - Guardians of the mycobacterial genome: A review on DNA repair systems in
      Mycobacterium tuberculosis.
AB  - The genomic integrity of Mycobacterium tuberculosis is continuously threatened by
      the harsh survival conditions inside host macrophages, due to immune and
      antibiotic stresses. Faithful genome maintenance and repair must be accomplished
      under stress for the bacillus to survive in the host, necessitating a robust DNA
      repair system. The importance of DNA repair systems in pathogenesis is well
      established. Previous examination of the M. tuberculosis genome revealed
      homologues of almost all the major DNA repair systems, i.e. nucleotide excision
      repair (NER), base excision repair (BER), homologous recombination (HR) and non
      homologous end joining (NHEJ). However, recent developments in the field have
      pointed to the presence of novel proteins and pathways in mycobacteria.
      Homologues of archeal mismatch repair proteins were recently reported in
      mycobacteria, a pathway previously thought to be absent. RecBCD, the major
      nuclease-helicase enzymes involved in HR in E. coli, were implicated in the
      single-strand annealing (SSA) pathway. Novel roles of archeo-eukaryotic primase
      (AEP) polymerases, previously thought to be exclusive to NHEJ, have been reported
      in BER. Many new proteins with a probable role in DNA repair have also been
      discovered. It is now realized that the DNA repair systems in M. tuberculosis are
      highly evolved and have redundant backup mechanisms to mend the damage. This
      review is an attempt to summarize our current understanding of the DNA repair
      systems in M. tuberculosis.

PMID- 29171824
TI  - Haem-iron plays a key role in the regulation of the Ess/type VII secretion system
      of Staphylococcus aureus RN6390.
AB  - The Staphylococcus aureus type VII protein secretion system (T7SS) plays
      important roles in virulence and intra-species competition. Here we show that the
      T7SS in strain RN6390 is activated by supplementing the growth medium with
      haemoglobin, and its cofactor haemin (haem B). Transcript analysis and secretion
      assays suggest that activation by haemin occurs at a transcriptional and a post
      translational level. Loss of T7 secretion activity by deletion of essC results in
      upregulation of genes required for iron acquisition. Taken together these
      findings suggest that the T7SS plays a role in iron homeostasis in at least some
      S. aureus strains.

PMID- 29171826
TI  - Tertiary care centre adherence to unified guidelines for management of
      periprosthetic joint infections: a gap analysis.
AB  - BACKGROUND: The success rate of surgical treatment for periprosthetic joint
      infection (PJI) remains inconsistent in the literature. Variability in PJI
      clinical guidelines and surgeon adherence to guidelines could affect treatment
      success. The objectives of this study were to appraise current recommendations
      for PJI management and develop a unified clinical standard of care, to perform a
      gap analysis of PJI cases in a tertiary institution to determine the rate of
      guideline adherence, and to determine if adherence to unified PJI guidelines
      affected 2-year treatment outcomes. METHODS: We appraised the PJI guidelines from
      3 academic medical societies, and consistent statements were aggregated. We
      retrospectively reviewed all PJI cases in a tertiary care institution. We defined
      PJI based on Musculoskeletal Infection Society PJI criteria. Surgeon adherence to
      preoperative, intraoperative, surgical and medical management guidelines was
      calculated, and we evaluated the association between guideline adherence and 2
      year treatment outcomes. RESULTS: The institutional rate of PJI was 1.13% (38 of
      3368). Treatment success was 57.8% at 2 years. Unified guideline adherence
      percentages varied substantially: 92% of patients had preoperative erythrocyte
      sedimentation rate and C-reactive protein, 97% had intraoperative tissue
      cultures, 42% had appropriate preoperative arthrocentesis, and 74% underwent
      guideline-appropriate surgery. Performing appropriate preoperative arthrocentesis
      significantly correlated with positive treatment outcomes at 2 years (p = 0.028).
      CONCLUSION: Adherence to PJI guidelines varies considerably, indicating that
      clinicians are either unaware of them or do not recognize their value for PJI
      treatment. This study shows the need for institution-based PJI treatment pathways
      that are consistent with published guidelines and the need to monitor adherence.

PMID- 29171827
TI  - Comparing the anterior, posterior and lateral approach: gait analysis in total
      hip arthroplasty.
AB  - BACKGROUND: The choice of surgical approach for total hip arthroplasty (THA)
      remains a contentious issue with regards to clinical outcome optimization and
      restoring patient function. The purpose of this study was to determine the impact
      of surgical approach for THA on quantitative gait analysis. METHODS: Patients
      undergoing THA for primary osteoarthritis of the hip were assigned to 1 of 3
      surgical approaches: anterior, posterior and lateral. Standardized implants were
      used at the time of surgery. Three-dimensional gait analysis was performed
      preoperatively and at 6 and 12 weeks postoperatively. At each time point, we
      compared temporal parameters, kinematics and kinetics. RESULTS: We included 30
      patients in our analysis (10 anterior, 10 posterior, and 10 lateral). The groups
      were similar with respect to age (p = 0.27), body mass index (p = 0.16), and
      Charlson Comorbidity Index score (p = 0.66). Temporal parameters were similar
      among the groups at all time points. The lateral cohort had higher pelvic tilt
      during stance on the affected leg than the anterior cohort at 6 weeks (p =
      0.041). Affected leg ipsilateral trunk lean during stance was higher in the
      lateral group than in the other cohorts at 6 weeks (p = 0.008) and 12 weeks (p =
      0.040). The anterior and posterior groups showed increased external rotation at 6
      weeks (p = 0.003) and 12 weeks (p = 0.012) compared with the lateral group.
      CONCLUSION: Temporal gait parameters were similar following THA for all
      approaches. Differences in gait kinematics and kinetics exist; however, given the
      small absolute differences, the clinical importance of these changes remains
      undetermined.

PMID- 29171828
TI  - Analysis of postdischarge costs following emergent general surgery in elderly
      patients.
AB  - BACKGROUND: As populations age, more elderly patients will undergo surgery.
      Frailty and complications are considered to increase in-hospital cost in older
      adults, but little is known on costs following discharge, particularly those
      borne by the patient. We examined risk factors for increased cost and the type of
      costs accrued following discharge in elderly surgical patients. METHODS: Acute
      abdominal surgery patients aged 65 years and older were prospectively enrolled.
      We assessed baseline clinical characteristics, including Clinical Frailty Scale
      (CFS) scores. We calculated 6-month cost (in Canadian dollars) from patient
      reported use following discharge according to the validated Health Resource
      Utilization Inventory. Primary outcomes were 6-month overall cost and cost for
      health care services, medical products and lost productive hours. Outcomes were
      log-transformed and assessed in multivariable generalized linear and zero
      inflated negative binomial regressions and can be interpreted as adjusted ratios
      (AR). Complications were assessed according to Clavien-Dindo classification.
      RESULTS: We included 150 patients (mean age 75.5 +/- 7.6 yr; 54.1% men) in our
      analysis; 10.8% had major and 43.2% had minor complications postoperatively. The
      median 6-month overall cost was $496 (interquartile range $140-$1948).
      Disaggregated by cost type, frailty independently predicted increasing costs of
      health care services (AR 1.76, 95% confidence interval [CI] 1.43-2.18, p < 0.001)
      and medical products (AR 1.61, 95% CI 1.15-2.25, p = 0.005), but decreasing costs
      in lost productive hours (AR 0.39, p = 0.002). Complications did not predict
      increased cost. CONCLUSION: Frail patients accrued higher health care services
      and product costs, but lower costs from lost productive hours. Interventions in
      elderly surgical patients should consider patient-borne cost in older adults and
      lost productivity in less frail patients. TRIAL REGISTRATION: NCT02233153
      (clinicaltrials.gov).

PMID- 29171829
TI  - Effect of patient decision aid was influenced by presurgical evaluation among
      patients with osteoarthritis of the knee.
AB  - BACKGROUND: Decision aids help patients make total joint arthroplasty decisions,
      but presurgical evaluation might influence the effects of a decision aid. We
      compared the effects of a decision aid among patients considering total knee
      arthroplasty at 2 surgical screening clinics with different evaluation processes.
      METHODS: We performed a subgroup analysis of a randomized controlled trial.
      Patients were recruited from 2 surgical screening clinics: an academic clinic
      providing 20-minute physician consultations and a community clinic providing 45
      minute physiotherapist/nurse consultations with education. We compared the
      effects of decision quality, decisional conflict and surgery rate using Cochran
      Mantel-Haenszel chi2 tests and the Breslow-Day test. RESULTS: We evaluated 242
      patients: 123 from the academic clinic (61 who used the decision aid and 62
      controls) and 119 from the community clinic (59 who used the decision aid and 60
      controls). Results suggested a between-site difference in the effect of the
      decision aid on the patients' decision quality (p = 0.09): at the academic site,
      patients who used the decision were more likely to make better-quality decisions
      than controls (54% v. 35%, p = 0.044), but not at the community site (47% v. 51%,
      p = 0.71). Fewer patients who used decision aids at the academic site than at the
      community site experienced decisional conflict (p = 0.007) (33% v. 52%, p = 0.05
      at the academic site and 40% v. 24%, p = 0.08 at the community site). The effect
      of the decision aid on surgery rates did not differ between sites (p = 0.65).
      CONCLUSION: The decision aid had a greater effect at the academic site than at
      the community site, which provided longer consultations with more verbal
      education. Hence, decision aids might be of greater value when more extensive
      total knee arthroplasty presurgical assessment and counselling are either
      impractical or unavailable.

PMID- 29171830
TI  - Process mapping as a framework for performance improvement in emergency general
      surgery.
AB  - BACKGROUND: Emergency general surgery conditions are often thought of as being
      too acute for the development of standardized approaches to quality improvement.
      However, process mapping, a concept that has been applied extensively in
      manufacturing quality improvement, is now being used in health care. The
      objective of this study was to create process maps for small bowel obstruction in
      an effort to identify potential areas for quality improvement. METHODS: We used
      the American College of Surgeons Emergency General Surgery Quality Improvement
      Program pilot database to identify patients who received nonoperative or
      operative management of small bowel obstruction between March 2015 and March
      2016. This database, patient charts and electronic health records were used to
      create process maps from the time of presentation to discharge. RESULTS: Eighty
      eight patients with small bowel obstruction (33 operative; 55 nonoperative) were
      identified. Patients who received surgery had a complication rate of 32%. The
      processes of care from the time of presentation to the time of follow-up were
      highly elaborate and variable in terms of duration; however, the sequences of
      care were found to be consistent. We used data visualization strategies to
      identify bottlenecks in care, and they showed substantial variability in terms of
      operating room access. CONCLUSION: Variability in the operative care of small
      bowel obstruction is high and represents an important improvement opportunity in
      general surgery. Process mapping can identify common themes, even in acute care,
      and suggest specific performance improvement measures.

PMID- 29171831
TI  - Physical performance following acute high-risk abdominal surgery: a prospective
      cohort study.
AB  - BACKGROUND: Acute high-risk abdominal (AHA) surgery is associated with high
      mortality, multiple postoperative complications and prolonged hospital stay.
      Further development of strategies for enhanced recovery programs following AHA
      surgery is needed. The aim of this study was to describe physical performance and
      barriers to independent mobilization among patients who received AHA surgery
      (postoperative days [POD] 1-7). METHODS: Patients undergoing AHA surgery were
      consecutively enrolled from a university hospital in Denmark. In the first
      postoperative week, all patients were evaluated daily with regards to physical
      performance, using the Cumulated Ambulation Score (CAS; 0-6 points) to assess
      basic mobility and the activePAL monitor to assess the 24-hour physical activity
      level. We recorded barriers to independent mobilization. RESULTS: Fifty patients
      undergoing AHA surgery (mean age 61.4 +/- 17.2 years) were included. Seven
      patients died within the first postoperative week, and 15 of 43 (35%) patients
      were still not independently mobilized (CAS < 6) on POD-7, which was associated
      with pulmonary complications developing (53% v. 14% in those with CAS = 6, p =
      0.012). The patients lay or sat for a median of 23.4 hours daily during the first
      week after AHA surgery, and the main barriers to independent mobilization were
      fatigue and abdominal pain. CONCLUSION: Patients who receive AHA surgery have
      very limited physical performance in the first postoperative week. Barriers to
      independent mobilization are primarily fatigue and abdominal pain. Further
      studies investigating strategies for early mobilization and barriers to
      mobilization in the immediate postoperative period after AHA surgery are needed.

PMID- 29171832
TI  - No. 3 Canadian General Hospital (McGill) in the Great War: service and sacrifice.
AB  - SUMMARY: During the Great War, McGill University fielded a full general hospital
      to care for the wounded and sick among the Allied forces fighting in France and
      Belgium. The unit was designated No. 3 Canadian General Hospital (McGill) and
      included some of the best medical minds in Canada. Because the unit had a
      relationship with Sir William Osler, who was a professor at McGill from 1874 to
      1885, the unit received special attention throughout the war, and legendary
      Canadian medical figures, such as John McCrae, Edward Archibald and Francis
      Scrimger, VC, served on its staff. The unit cared for thousands of victims of the
      war, and its trauma care advanced through the clinical innovation and research
      demanded by the nature of its work. Although No. 3 Canadian General Hospital
      suffered tragedies as well, such as the deaths of John McCrae and Osler's only
      son Revere, by the war's end the McGill hospital was known as one of the best
      medical units within the armies in France.

PMID- 29171833
TI  - Patient-perceived barriers to radiation therapy for breast cancer.
AB  - SUMMARY: Studies have shown that a number of women do not receive adjuvant
      radiation therapy following breast-conserving surgery; the reasons have not been
      well investigated. We reviewed the charts of 267 patients in our institution who
      did not receive radiation therapy following surgery in order to determine
      patientstated reasons for nonreceipt. We found that 43% of patients did not
      receive radiation because they received a completion mastectomy. Excluding these
      patients, reasons for nonreceipt of radiation therapy were sorted into 9
      categories. Most patients declined radiation therapy (against physician advice).
      We identified 3 major barriers to receipt of radiation therapy: improper patient
      selection, transportation or ambulatory issues and patient fear surrounding
      radiation toxicity. All of these reasons are surmountable barriers to radiation
      receipt.

PMID- 29171834
TI  - The genome of an intranuclear parasite, Paramicrosporidium saccamoebae, reveals
      alternative adaptations to obligate intracellular parasitism.
AB  - Intracellular parasitism often results in gene loss, genome reduction, and
      dependence upon the host for cellular functioning. Rozellomycota is a clade
      comprising many such parasites and is related to the diverse, highly reduced,
      animal parasites, Microsporidia. We sequenced the nuclear and mitochondrial
      genomes of Paramicrosporidium saccamoebae [Rozellomycota], an intranuclear
      parasite of amoebae. A canonical fungal mitochondrial genome was recovered from
      P. saccamoebae that encodes genes necessary for the complete oxidative
      phosphorylation pathway including Complex I, differentiating it from most
      endoparasites including its sequenced relatives in Rozellomycota and
      Microsporidia. Comparative analysis revealed that P. saccamoebae shares more gene
      content with distantly related Fungi than with its closest relatives, suggesting
      that genome evolution in Rozellomycota and Microsporidia has been affected by
      repeated and independent gene losses, possibly as a result of variation in
      parasitic strategies (e.g. host and subcellular localization) or due to multiple
      transitions to parasitism.

PMID- 29171835
TI  - Sequestration and activation of plant toxins protect the western corn rootworm
      from enemies at multiple trophic levels.
AB  - Highly adapted herbivores can phenocopy two-component systems by stabilizing,
      sequestering and reactivating plant toxins. However, whether these traits protect
      herbivores against their enemies is poorly understood. We demonstrate that the
      western corn rootworm Diabrotica virgifera virgifera, the most damaging maize
      pest on the planet, specifically accumulates the root-derived benzoxazinoid
      glucosides HDMBOA-Glc and MBOA-Glc. MBOA-Glc is produced by D. virgifera through
      stabilization of the benzoxazinoid breakdown product MBOA by N-glycosylation. The
      larvae can hydrolyze HDMBOA-Glc, but not MBOA-Glc, to produce toxic MBOA upon
      predator attack. Accumulation of benzoxazinoids renders D. virgifera highly
      resistant to nematodes which inject and feed on entomopathogenic symbiotic
      bacteria. While HDMBOA-Glc and MBOA reduce the growth and infectivity of both the
      nematodes and the bacteria, MBOA-Glc repels infective juvenile nematodes. Our
      results illustrate how herbivores combine stabilized and reactivated plant toxins
      to defend themselves against a deadly symbiosis between the third and the fourth
      trophic level enemies.

PMID- 29171836
TI  - CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes
      immunological tolerance in NOD mice, via a dual role in effector and regulatory T
      cells.
AB  - How tissue-resident macrophages (TRM) impact adaptive immune responses remains
      poorly understood. We report novel mechanisms by which TRMs regulate T cell
      activities at tissue sites. These mechanisms are mediated by the complement
      receptor of immunoglobulin family (CRIg). Using animal models for autoimmune type
      1 diabetes (T1D), we found that CRIg+ TRMs formed a protective barrier
      surrounding pancreatic islets. Genetic ablation of CRIg exacerbated islet
      inflammation and local T cell activation. CRIg exhibited a dual function of
      attenuating early T cell activation and promoting the differentiation of Foxp3+
      regulatory (Treg) cells. More importantly, CRIg stabilized the expression of
      Foxp3 in Treg cells, by enhancing their responsiveness to interleukin-2. The
      expression of CRIg in TRMs was postnatally regulated by gut microbial signals and
      metabolites. Thus, environmental cues instruct TRMs to express CRIg, which
      functions as an immune checkpoint molecule to regulate adaptive immunity and
      promote immune tolerance.

PMID- 29171838
TI  - Frailty: is thy name.....universal? Evolving challenges of managing effectively
      treated older people living with HIV.
AB  - The increased survival of treated people living with HIV (PLWH) represents a
      tremendous accomplishment. However, this has not been accompanied by uniform
      improvements in quality of life. Many PLWH prematurely develop age-related
      complications and traditional geriatric syndromes, including frailty. This is a
      potentially reversible state of vulnerability to adverse outcomes. Its
      operationalization remains challenging. The most commonly used tools, the frailty
      phenotype and the frailty index, have their advantages and limitations, but
      predict similar poor outcomes. Yeoh et al. applied both metrics, and a simpler
      construct, the Edmonton Frail Scale, to a population of Australian PLWH. Although
      the prevalence of frailty was generally similar to that in other settings,
      distinct differences occurred between the tools. This paper adds to the
      literature on this serious condition in this already vulnerable population.
      Further research is needed before consensus is reached on how to reliably and
      simply diagnose frailty in PLWH.

PMID- 29171839
TI  - Primary pericardial mesothelioma in a 48-year-old patient.

PMID- 29171837
TI  - Inflammation investigated as a source of pharmacokinetic variability of
      atazanavir in AIDS Clinical Trials Group protocol A5224s.
AB  - BACKGROUND: Inflammation is associated with the downregulation of drug
      metabolizing enzymes and transporters. Thus, we investigated the chronic
      inflammatory state associated with HIV infection as a source of pharmacokinetic
      variability of atazanavir. We also explored the association of total bilirubin
      concentrations with markers of inflammation and endothelial activation. METHODS:
      Apparent oral clearance (CL/F) of atazanavir was estimated from plasma samples
      collected from participants in AIDS Clinical Trials Group Study A5202. Several
      inflammatory and endothelial activation biomarkers were measured at baseline and
      weeks 24 and 96 as part of metabolic substudy A5224s: high-sensitivity C-reactive
      protein (hsCRP), interleukin-6, tumour necrosis factor-alpha and its soluble
      receptors, soluble vascular cellular and intracellular adhesion molecules and
      total bilirubin. Statistical analysis was performed by a matrix of correlation
      coefficients between atazanavir CL/F and biomarker concentrations measured at
      week 24. The correlation between atazanavir clearance and percentage change in
      bilirubin from baseline to weeks 24 and 96, and between biomarkers and bilirubin
      concentrations at each week were also evaluated. RESULTS: Among 107 participants,
      there were no significant correlations observed between atazanavir CL/F and
      inflammatory and endothelial activation biomarkers measured at week 24 (P>=0.24).
      As expected, bilirubin increased with increasing exposure to atazanavir (rho=
      0.25, P=0.01). Bilirubin concentrations were inversely correlated (P<0.01) with
      each of the biomarkers except hsCRP. CONCLUSIONS: Atazanavir CL/F did not
      correlate with the inflammatory biomarkers changes. Inflammatory-mediated
      inhibition of cytochrome P450 3A may have been attenuated due to atazanavir
      associated increases of bilirubin, which has known anti-inflammatory properties.

PMID- 29171840
TI  - What intrinsic and extrinsic factors explain the stoichiometric diversity of
      aquatic heterotrophic bacteria?
AB  - The elemental content of microbial communities is dependent upon the physiology
      of constituent populations, yet ecological stoichiometry has made slow progress
      toward identifying predictors of how species and strains change the elemental
      content of their biomass in response to the stoichiometry of elements in
      resources. We asked whether the elemental content of aquatic bacteria, especially
      flexibility in elemental content, could be predicted by their phylogeny, maximum
      growth rate or lake productivity. We examined 137 isolates using chemostats and
      found that strains differed substantially in how the carbon:nitrogen:phosphorus
      ratios (C:N:P) in their biomass responded to P-sufficient and P-limiting
      conditions. The median strain increased its biomass C:N:P from 68:14:1 to
      164:25:1 under P limitation. Patterns in elemental content and ratios were partly
      explained by phylogeny, yet flexibility in elemental content showed no
      phylogenetic signal. The growth rate hypothesis predicts that P content is
      positively related to growth rate, but we found weak correlation between maximum
      growth rate and P content among the strains. Overall, isolates from highly
      productive lakes had higher maximum growth rates and less flexible biomass N:P
      than isolates from unproductive lakes. These results show that bacteria present
      within lake communities exhibit diverse strategies for responding to elemental
      imbalance.

PMID- 29171841
TI  - Verification of electronic device technology for measurement and evaluation of
      thermal exposure of fire fighters and members of rescue teams.
AB  - BACKGROUND: The work of members of rescue teams could be associated with very
      high physical and thermal loads. If not timely interrupted, any extreme labour
      thermal load may lead to a failure of the body and fatal collapse. This risk may
      be significantly reduced by devices that monitor the response of the body during
      the intervention and inform rescuers about the need to interrupt the exposure
      when the critical value of the reference indicator is achieved. The aim of the
      study was to test the correlation between the data of the newly developed device
      for signaling the strain of rescuers and the indicators of physiological response
      of the body. MATERIAL AND METHODS: The tests were performed on 2 physically fit
      fire fighters dressed in a protective rescue suit and using insulating breathing
      apparatus, over a wide range of heat load under a model load on a bicycle
      ergometer in a climatic chamber. RESULTS: The study provided a significant
      correlation between the body temperature measured in the ear canal and the
      temperature under the suit sensed by the tested device - the Safety Ambient
      Monitor (SAM) (R = 0.9007). The temperature under the suit also correlated with
      the temperature of the chest skin (R = 0.8928) and heart rate (R = 0.8613).
      CONCLUSIONS: A statistically significant correlation was proven between the
      temperature sensed by the SAM and the body temperature. The technical solution of
      sensing the temperature under the suit using the verified SAM technology does not
      affect or limit fire fighters in their work and minimizes the possibility of
      damage to the sensor and signaling failures. Med Pr 2018;69(1):1-11.

PMID- 29171842
TI  - [Assessment of work environment vs. feeling of threat and aggravation of stress
      in job of a high risk - An attempt of organizational intervention].
AB  - BACKGROUND: The main purpose of this article was to examine, whether and to what
      extend an assessment of work environment and feeling of threat are associated
      with stress at work performed in health- and life-threatening conditions.
      Previous studies of the determinants of occupational stress have been carried out
      in relation to representatives of different occupational groups that are not,
      however, representatives of one organization. The research was also meant to
      provide practical guidance for a particular employer. MATERIAL AND METHODS: The
      study was carried out in the factory of explosives. It involved 95 randomly
      selected employees of the production departments. Subjective evaluation of work
      was performed by the examined persons in the Areas of Worklife Survey. It allows
      to assess the functioning of the employee in the workplace and to recognize the
      discrepancies between the requirements of the organization and the needs,
      aspirations and abilities of the examined person. Feeling of insecurity at work
      was defined by using the Feeling of Danger at Work Survey. The level of stress
      was assessed using the Perceived Stress Scale (PSS-10). RESULTS: The workload and
      feeling of danger are relevant to the stress felt by the employees. The workload
      is also the mediator of the relations between the sense of danger and the stress
      felt by the examined employees. CONCLUSIONS: At the level of manufacturing
      process management in an organization, there is a need to reduce the negative
      impact of physical and mental strain associated with haste and uncertainty. Med
      Pr 2018;69(1):45-58.

PMID- 29171843
TI  - Resistance of gloves and protective clothing materials to permeation of
      cytostatic solutions.
AB  - OBJECTIVES: The objective of the work was to determine the resistance of selected
      protective clothing and glove materials to permeation of cytostatics such as
      docetaxel, fluorouracil, and doxorubicin. MATERIAL AND METHODS: The following
      glove materials were used: natural rubber latex (code A), acrylonitrile-butadiene
      rubber (code B) and chloroprene rubber (code C). In addition, we tested a layered
      material composed of a non-woven polyester (PES), a polypropylene (PP) film, and
      a non-woven PP used for protective coats (code D). The cytostatics were analyzed
      by liquid chromatography with diode array detection. The tested samples were
      placed in a purpose-built permeation cell modified to be different from that
      specified in the standard EN 6529:2001. RESULTS: The tested materials were
      characterized by good resistance to solutions containing 2 out of the 3 selected
      cytostatics: doxorubicin and 5-fluorouracil, as indicated by a breakthrough time
      of over 480 min. Equally high resistance to permeation of the third cytostatic
      (docetaxel) was exhibited by natural rubber latex, acrylonitrile-butadiene
      rubber, and chloroprene rubber. However, docetaxel permeated much more readily
      through the clothing layered material, compromising its barrier properties.
      CONCLUSIONS: It was found that the presence of additional components in
      cytostatic preparations accelerated permeation through material samples, thus
      deteriorating their barrier properties. Int J Occup Med Environ Health
      2018;31(3):341-350.

PMID- 29171844
TI  - Mutual diffusion governed by kinetics and thermodynamics in the partially
      miscible mixture methanol + cyclohexane.
AB  - To gain an understanding of the transport and thermodynamic behavior of the
      highly non-ideal mixture methanol + cyclohexane, three complementary approaches,
      i.e. experiment, molecular simulation and predictive equations, are employed. The
      temperature and composition dependence of different diffusion coefficients is
      studied around the miscibility gap at ambient pressure. On the one hand Fick
      diffusion coefficients are measured experimentally by interferometric probing and
      on the other hand Maxwell-Stefan diffusion coefficients and intradiffusion
      coefficients are sampled by equilibrium molecular dynamics simulation at five
      temperatures below the upper critical temperature of ~319 K. The spinodal curve
      is determined from extrapolation of the experimental Fick diffusion coefficient
      data and compared to predictions from excess Gibbs energy models. It is found
      that these models are not capable to correctly describe the activity coefficients
      over the whole composition range of the studied mixture. Thus, different
      parameter sets for a modified Wilson model are used for calculations of the
      thermodynamic factor, which is needed to transform Maxwell-Stefan into Fick
      diffusion coefficients and vice versa. Further, predictive equations for the
      Maxwell-Stefan diffusion coefficient, which are based on intradiffusion
      coefficients, are compared to simulation results. Using different approaches
      provides a clearer understanding of the relations between kinetic and
      thermodynamic properties contributing to the diffusion behavior of partially
      miscible mixtures.

PMID- 29171845
TI  - Unusual intramolecular CHO hydrogen bonding interaction between a sterically
      bulky amide and uranyl oxygen.
AB  - The selective separation of toxic heavy metals such as uranyl can be accomplished
      using ligands with stereognostic hydrogen bonding interactions to the uranyl oxo
      group, as proposed by Raymond and co-workers (T. S. Franczyk, K. R. Czerwinski
      and K. N. Raymond, J. Am. Chem. Soc., 1992, 114, 8138-8146). Recently, several
      ligands possessing this weak interaction have been proposed involving the
      hydrogen bonding of NH and OH based moieties with uranyl oxygen. We herein report
      the structurally and spectroscopically characterized CHO hydrogen bonding using a
      sterically bulky amide based ligand. In conjunction with experiments, electronic
      structure calculations are carried out to understand the structure, binding and
      the strength of the CHO hydrogen bonding interactions. This weak interaction is
      mainly due to the steric effect caused by a bulky substituent around the donor
      group which has direct relevance in designing novel ligands in nuclear waste
      management processes. Although the kinetics are very slow, the ligand is also
      highly selective to uranyl in the presence of other interfering ions such as
      lanthanides.

PMID- 29171846
TI  - Sm(iii)[12-MCGa(III)shi-4] as a luminescent probe for G-quadruplex structures.
AB  - G-quadruplexes (GQs), spatial assemblies of guanine-rich DNA strands, play an
      important role in the regulation of gene expression and chromosome stabilization.
      These structures are recognized to be useful in cancer therapies as the presence
      of multiple G-quadruplexes in a telomeric strand stops cancer cell proliferation.
      Metallacrowns of the type 12-MC-4 form planar structures that have remarkable
      similarity to G-tetrads in terms of dimension, shape and the ability to bind
      alkali metal and lanthanide cations in a central cavity. The interaction between
      the Sm(iii)[12-MCGa(III)shi-4] (SmMC) metallacrown (MC) and human telomeric G
      quadruplex structures was examined using several methods including CD titrations,
      CD melting temperatures, fluorescence titration of SmMC with GQ/Na+, fluorescence
      intercalator displacement (FID) assays and methods measuring the MC quenching
      effect on the Tb3+/GQ luminescence. It was proven that the studied metallacrown
      acted as a sensing probe and interacted with quadruplex DNA. The Stern-Volmer
      quenching constant (Kas) of Tb3+/GQ luminescence was calculated to be 3.9 * 105 M
      1. The binding constant using the indirect FID method gave the result of 1.3 *
      105 M-1. CD melting temperature experiments reveal the following pattern - the
      higher the concentration of the complex the lower the registered Tm for
      quadruplex DNA, which indicates a destabilizing effect of SmMC at higher GQ : MC
      ratios. These data implicate a shape and size selective interaction between MCs
      and GQs that may be exploited for telomere detection.

PMID- 29171847
TI  - A multifunctional Ni(ii) coordination polymer: synthesis, crystal structure and
      applications as a luminescent sensor, electrochemical probe, and photocatalyst.
AB  - Herein, a nickel coordination polymer (CP 1), {Ni(1,4-bib)1.5(TPA-Cl2).H2O}n (1,4
      bib = 1,4-bis(1H-imidazol-1-yl)benzene, H2TPA-Cl2 = 2,5-dichloro-terephthalic
      acid), has been synthesized under solvothermal conditions. The structure of CP 1
      is a 3D 3-fold interpenetrating framework with the sqc12 topology. The thermal
      stability and luminescence properties of CP 1 were investigated. Scanning
      electron microscopy (SEM) images of this material display that it possesses an
      irregular block 3D structure. Interestingly, CP 1 can serve as a multifunctional
      material via its luminescence sensing, electrochemical sensing, and
      photocatalytic properties. The experimental results indicate that CP 1 is an
      efficient luminescent sensor for the detection of Fe3+ ions in an aqueous
      solution. In addition, CP 1 exhibits a sensitive and rapid electrochemical
      response to nitrite ions in water solution. The photocatalytic activities of CP 1
      were evaluated in the degradation of different dye contaminants (MB, RhB, and
      MO), and the results demonstrate that its photocatalytic efficiency for the
      degradation of MB is highest (92.1% for MB, 85.7% for RhB, and 86.2% for MO). The
      effects of different dyes, different powers of UV light, and different amounts of
      catalyst CP 1 on the photocatalytic efficiency were also explored. Finally, the
      mechanism of the luminescence quenching effect toward Fe3+ ions, electroreduction
      of nitrite ions, and photocatalytic degradation of different dyes have been
      investigated in detail.

PMID- 29171849
TI  - Uracil removal-inhibited ligase reaction in combination with catalytic hairpin
      assembly for the sensitive and specific detection of uracil-DNA glycosylase
      activity.
AB  - Sensitive and specific detection of uracil-DNA glycosylase (UDG) activity is
      crucial in biomedical study and disease diagnosis. Here, we developed a uracil
      removal-inhibited ligase reaction in combination with catalytic hairpin assembly
      (CHA) for the sensitive and specific detection of UDG activity. A hairpin probe
      is specially designed, which contains two uracil bases in the loop and is
      extended with toehold and branch-migration domains at the ends of the stem. Two
      short oligonucleotides are separately hybridized to one-half of the loop of the
      hairpin probe to form a DNA complex with a nick. Under the action of UDG, two
      uracil bases in the hairpin-loop are removed to generate apurinic/apyrimidinic
      (AP) sites. The AP sites locating at the 3'-side of the nick inhibit the ligase
      reaction, leaving the toehold and branch-migration domains at the ends of the
      hairpin probe still adjacent. The adjacent toehold and branch-migration domains
      initiate CHA, producing numerous G-quadruplex (G4) structures, which interact
      with N-methyl-mesoporphyrin IX (NMM) to generate an enhanced fluorescence signal.
      The excessive probes would be masked by the ligase reaction that closes the nick
      and forms a long DNA strand fully complementary to the hairpin domain. The probes
      then get opened and the toehold/branch-migration domains are not associated,
      prohibiting the CHA reaction and minimizing false-positive interferences. The
      detection limit is as low as 0.00028 U mL-1, and UDG can be well distinguished
      from other DNA glycosylases. Furthermore, this method is successfully applied for
      detecting UDG activity from HeLa cell lysates. Additionally, the inhibition of
      UDG activity is analyzed, which shows inhibitor dose-dependent activity
      suppression. This strategy will provide a promising tool for assaying UDG
      activity in biomedical study and disease diagnosis.

PMID- 29171848
TI  - A pilot study on clinical pharmacokinetics and preclinical pharmacodynamics of
      (+)-epicatechin on cardiometabolic endpoints.
AB  - We reported that (-)-epicatechin can stimulate mitochondria biogenesis and
      improve metabolism. However, preliminary studies indicate that the (+)
      stereoisomer form may be more potent. We evaluated in a preliminary manner, the
      pharmacokinetics (PK) and initial safety analysis of (+)-epicatechin ((+)-Epi) in
      healthy and pre-diabetic subjects. Using a mouse model of diet-induced obesity
      and insulin resistance, we also evaluated the metabolic effects of (+)-Epi vs.
      (+)-catechin (Cat) to determine class effects. In the Phase I PK study, subjects
      were provided a single incremental oral dose of (+)-Epi (10, 30 or 100 mg). For
      the PD study, subjects were provided a single 30 mg dose per day for 7 days.
      Blood samples were collected and safety measures were performed. Incremental
      doses of (+)-Epi increase the half-life of blood metabolites from 1.2-4.9 h. The
      compound was well tolerated and no adverse effects were reported. Seven day
      dosing of pre-diabetic subjects led to tendencies for reductions in circulating
      levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1,
      which returned to baseline by 7 days after treatment. In animals, 2 weeks of oral
      dosing (0.003, 0.01, 0.03, 0.1 and 0.3 mg kg-1 day-1) dose dependently improved
      metabolism-related endpoints (weight gain, glucose, cholesterol, triglyceride,
      with thresholds as low as 0.01 mg kg-1 day-1). Cat yielded no effects at 0.1 mg
      kg-1 day-1. Results indicate that (+)-Epi evidences a favorable PK and safety
      profile. Using a pre-clinical model, the compound positively modulates
      metabolism, which may link to mitochondrial effects. Effects are not due to
      general antioxidant actions, as Cat yielded no effects.

PMID- 29171850
TI  - Intercalative hybridization of layered double hydroxide nanocrystals with
      mesoporous g-C3N4 for enhancing visible light-induced H2 production efficiency.
AB  - Efficient visible light active hybrid photocatalysts for H2 production can be
      synthesized by the intercalative hybridization of Zn-Cr-layered double hydroxide
      (Zn-Cr-LDH) with a mesoporous g-C3N4 lattice. Small Zn-Cr-LDH nanocrystals with a
      size of ~6 nm are immobilized in the mesopores of g-C3N4. Beyond an optimal LDH/g
      C3N4 molar ratio of 0.3, a further increase in the LDH content leads to the
      surface deposition of LDH crystals on the g-C3N4 material as well as the
      intercalative immobilization of LDH into its mesopores, indicating the
      controllability of the LDH deposition site. The Zn-Cr-LDH-g-C3N4 nanohybrids
      exhibit smaller surface areas than the pristine g-C3N4, confirming the
      intercalative stabilization of Zn-Cr-LDH nanocrystals in the mesopore of g-C3N4.
      The hybridization between Zn-Cr-LDH and g-C3N4 is effective in enhancing visible
      light absorptivity and also in depressing electron-hole recombination, which is
      attributable to an efficient electronic coupling between both the hybridized
      components. The present Zn-Cr-LDH-g-C3N4 nanohybrid exhibits promising
      photocatalytic activities for visible light-induced H2 production at a rate of
      155.7 MUmol g-1 h-1, which is much superior to that of the pristine g-C3N4 (21.7
      MUmol g-1 h-1). The present study underscores that the intercalative
      immobilization of Zn-Cr-LDH crystals in the limited space of a mesopore is quite
      useful in improving the visible light active photocatalyst functionality of
      mesoporous carbon nitride.

PMID- 29171851
TI  - A facile and universal strategy for preparation of long wavelength emission
      carbon dots.
AB  - Carbon dots (CDs) have emerged as a promising new type of fluorescent
      nanomaterial, although one of their main problems is the tuning of the emission
      wavelength toward the long wavelength region. In this work, the influence of
      reaction solvents to emission of CDs was systematically studied using four groups
      of classical precursors (citric acid individually mixed with four nitrogenous
      organic compounds). Water and toluene were selected to represent the hydrophobic
      and hydrophilic reaction medium, respectively. It is interesting to observe that
      in toluene solvent, all the CD products yield two emission bands of blue and
      yellow light, and the relative intensity of the yellow to blue can be finely
      tuned by the precursors. In contrast, the CDs formed in water only demonstrate
      blue emission. Systematic studies indicate that the spectral change results from
      the content control of carbogenic/defect states to surface states and the energy
      transfer from the carbogenic/defect states to the surface states. Moreover, solid
      state luminescent CD-polymers were fabricated that also demonstrated continuously
      tunable emission properties. This work provides a new strategy for recognizing
      the generation of long wavelength-emitting CDs.

PMID- 29171852
TI  - Steering on-surface reactions with self-assembly strategy.
AB  - The control of assembly structures that subsequently help achieve viable
      functionalities has been one of the key motivations for the exploration of
      surface molecular assembly. In terms of its functionality and applicability, the
      assembly is explored as a strategy to steer on-surface reactions primarily by two
      methods: assembly-assisted and assembly-involved reactions. The functions of the
      self-assembly strategy are threefold: tweaking reaction selectivities, steering
      reaction pathways, and directing reaction sites. The governing principle herein
      is that the assembly strategy can apply a surface confinement effect that affects
      the energy barrier and pre-exponential factor of the Arrhenius equation for the
      dynamics of the target reaction. Development of such a strategy may reveal new
      routes to steer on-surface reactions and even single molecule properties in
      surface chemistry.

PMID- 29171853
TI  - Lamellar zirconium phosphates to host metals for catalytic purposes.
AB  - In the present study a porous lamellar zirconium phosphate heterostructure (PPH)
      formed from zirconium(iv) phosphate expanded with silica galleries (P/Zr molar
      ratio equal to 2 and (Si + Zr)/P equal to 3) was prepared to host noble metals.
      Textural and structural characterization of PPH-noble metal materials was carried
      out in order to elucidate the location and dispersion of the metallic particles
      and the properties of the resulting material to be used in catalytic processes.
      In the present paper, their activity in the catalytic hydrodeoxygenation (HDO)
      reaction of dibenzofuran (DBF) was evaluated. X-ray diffraction (XRD), solid
      state nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS)
      evidenced that the structure of the pillared zirconium phosphate material was not
      modified by the incorporation of Pt and Pd. Moreover, transmission electron
      microscopy (TEM) showed a different dispersion of the noble metal. The acidity of
      the resulting PPH-noble metal materials also changed, although in all cases the
      acidity was of weak nature, and the incorporation of noble metals affected
      Bronsted acid sites as observed from 31P NMR spectra. In general, the textural,
      structural and acidic properties of the resulting materials suggest that PPH can
      be considered a good candidate to be used as a catalytic support. Thus, the
      catalytic results of the PPH-noble metal samples indicated that the Pd sample
      showed a stable behavior probably ascribed to a high dispersion of the active
      phase. However, the Pt sample suffered from fast deactivation. The selectivity to
      the reaction products was strongly dependent on the noble metal employed.

PMID- 29171854
TI  - Preparation and characterization of terdentate [C,N,N] acetophenone and
      acetylpyridine hydrazone platinacycles: a DFT insight into the reaction
      mechanism.
AB  - The reaction of N-ortho-chlorophenyl-substituted acetylpyridine hydrazones (a and
      d) with K2[PtCl4] (n-butanol/water, 100  degrees C) gave mononuclear complexes 1a
      and 1d with the ligands as [N,N] bidentate. In contrast, the reaction of N-phenyl
      or N-meta-chlorophenyl hydrazones (b and c, respectively) under analogous
      reaction conditions gave the cycloplatinated species 2b and 2c with the ligand as
      [C,N,N] terdentate. The treatment of the mononuclear complexes 1a and 1d with
      NaOAc (n-butanol, 100  degrees C) gave the corresponding cycloplatinated
      complexes 2a and 2d. Acetophenone hydrazone platinacycle 2e was prepared in a
      similar fashion and its reaction with tertiary mono- and triphosphines gave mono-
      or trinuclear species depending on the reaction conditions. The X-ray crystal
      structures of some of these complexes showed interesting pi-pi slipped stacking
      interactions between metallacyclic rings which, according to NCI analyses, showed
      an aromatic character. With an aim to rationalize the different reactivities
      shown by acetylpyridine hydrazones and the precise role of the acetate anion, the
      energy profiles for the three main steps of cycloplatination (iminoplatinum
      complex formation, chelation and cyclometallation) have been determined by using
      the DFT (M06) methods. Calculations indicate that the cycloplatination of 1b
      proceeds via electrophilic substitution, involving the direct replacement of the
      chloride anion at the Pt(ii) centre with the N-phenyl moiety as the rate
      determining step, to give an agostic intermediate 5b+ that, subsequently, leads
      to the elimination of a proton as hydrogen chloride. When present as an
      "external" base, acetate enters the coordination sphere around the Pt(ii) centre
      and facilitates hydrazone N-H deprotonation and electrophilic C-H activation
      through a dissociative route, leading to a Wheland-type sigma-complex
      intermediate 9ac.

PMID- 29171855
TI  - A gel aging effect in the synthesis of open-framework gallium phosphates:
      structure solution and solid-state NMR of a large-pore, open-framework material.
AB  - The templated zeolite-analogue GaPO-34 (CHA structure type) crystallises from a
      gel precursor Ga2O3 : 2H3PO4 : 1HF : 1.7SDA : 70H2O (where SDA = structure
      directing agent), treated hydrothermally for 24 hours at 170  degrees C using
      either pyridine or 1-methylimizadole as SDA and one of either poorly crystalline
      epsilon-Ga2O3 or gamma-Ga2O3 as gallium precursor. If the same gels are stirred
      for periods shorter than 2 hours but treated under identical hydrothermal
      conditions, then a second phase crystallises, free of GaPO-34. If beta-Ga2O3 is
      used as a reagent only the second phase is found to crystallise, irrespective of
      gel aging time. The competing phase, which we denote GaPO-34A, has been
      structurally characterised using synchrotron powder X-ray diffraction for the
      pyridine material, GaPO-34A(pyr), and using single-crystal X-ray diffraction for
      the 1-methylimiazole material, GaPO-34A(mim). The structure of GaPO-34A(pyr),
      P1[combining macron], a = 10.22682(6) A, b = 12.09585(7) A, c = 13.86713(8) A,
      alpha = 104.6531(4) degrees , beta = 100.8111(6) degrees , gamma = 102.5228(6)
      degrees , contains 7 unique gallium sites and 6 phosphorus sites, with empirical
      formula [Ga7P6O24(OH)2F3(H2O)2].2(C5NH6). GaPO-34A(mim) is isostructural but is
      modelled as a half volume unit cell, P1[combining macron], a = 5.0991(2) A, b =
      12.0631(6) A, c = 13.8405(9) A, alpha = 104.626(5) degrees , beta = 100.346(5)
      degrees , gamma = 101.936(4) degrees , with a gallium and a bridging fluoride
      partially occupied and two partially occupied SDA sites. Solid-state 31P and 71Ga
      NMR spectroscopy confirms the structural complexity of GaPO-34A with signals
      resulting from overlapping lineshapes from multiple Ga and P sites, while 1H and
      13C solid-state NMR spectra confirm the presence of the protonated SDA and
      provide evidence for disorder in the SDA. The protonated SDA is located in 14
      ring one-dimensional channels with hydrogen bonding deduced from the SDA
      nitrogens to framework oxygen distances. Upon thermal treatment to investigate
      SDA removal, structure collapse occurs, which may be due the large number of
      bridging hydroxides and fluorides in the as-made material, and the unequal
      amounts of gallium and phosphorus present.

PMID- 29171856
TI  - 2-Acyl-1,1,3,3-tetracyanopropenides (ATCN): structure characterization and
      luminescence properties of ammonia and alkali metal ATCN salts.
AB  - Herein, syntheses, crystal structures, and photoluminescence properties of 24 new
      ammonia and alkali metal ATCN salts characterized via single-crystal X-ray
      diffraction are reported. Moreover, ten structure types of these salts have been
      described, three of which are predominant. Some ATCNs were obtained as two
      crystalline polymorphs. It was estimated that most ATCN powders exhibited yellow
      green fluorescence (at 450-600 nm). For samples that possess fluorescence of low
      intensity in the solid state, several optical centers of emission exist. It was
      speculated that the obtained spectral features were due to anion-anion
      intermolecular interactions. ATCN being a new representative of stable
      tetracyanoallyl salts is a promising candidate for creation of various 1D, 2D,
      and 3D supramolecular structures and potential functional materials.

PMID- 29171857
TI  - Metal-assisted exfoliation of few-layer black phosphorus with high yield.
AB  - We introduce a metal-assisted exfoliation method to produce few-layer black
      phosphorus with the lateral size larger than 50 MUm and the area 100 times larger
      than those exfoliated using the normal "scotch-tape" technique. Using a field
      effect transistor it was found the hole mobility is 68.6 cm2 V-1 s-1 and the
      current on/off ratio can reach about 2 * 105.

PMID- 29171858
TI  - Advances in single quantum dot-based nanosensors.
AB  - Single-molecule detection provides a simple and ultrasensitive platform to
      quantify target molecules by simply counting the individual fluorescence signals.
      Quantum dots (QDs) are novel semiconductor nanocrystals with distinct
      characteristics of high brightness, large Stokes shift and broad absorption
      spectra, high molar extinction coefficients, high quantum yield, good
      photostability and long fluorescence lifetime. The combination of single-molecule
      detection with QDs enables the development of single QD-based nanosensors with
      extremely high sensitivity. Single QD-based nanosensors may be divided into two
      categories based on single QD burst coincidence detection and single QD
      fluorescence resonance energy transfer (FRET) detection, and have significant
      advantages of high signal-to-noise ratio, high sensitivity, rapidity, and low
      sample consumption. The single QD-based nanosensors have the capability of
      directly detecting low-abundance species without the need for nucleic acid
      amplification, and may elucidate a variety of biological and biochemical
      phenomena in real time using single QD tracking. In this review, we summarize the
      recent advances in single QD-based nanosensors and their applications for
      sensitive detection of DNAs, microRNAs, proteins, enzymes, small molecules and
      viruses. We highlight the challenges and future direction of single QD-based
      nanosensors as well.

PMID- 29171859
TI  - Acute acalculous cholecystitis during zika virus infection in an
      immunocompromised patient.

PMID- 29171860
TI  - Demonstration tests of irrigation water disinfection with chlorine dioxide in
      open field cultivation of baby spinach.
AB  - BACKGROUND: Treatments for the disinfection of irrigation water have to be
      evaluated by demonstration tests carried out under commercial settings taking
      into account not only their antimicrobial activity but also the potential
      phytotoxic effects on the crop. The consequences of the treatment of irrigation
      water with chlorine dioxide (ClO2 ) used for sprinkler irrigation of baby spinach
      in two commercial agricultural fields was assessed. RESULTS: Residual ClO2 levels
      at the sprinklers in the treated field were always below 1 mg L-1 . ClO2
      treatment provoked limited but statistically significant reductions in culturable
      Escherichia coli counts (0.2-0.3 log reductions), but not in the viable E. coli
      counts in water, suggesting the presence of viable but non-culturable cells
      (VBNC). Although disinfected irrigation water did not have an impact on the
      microbial loads of Enterobacteriaceae nor on the quality characteristics of baby
      spinach, it caused the accumulation of chlorates (up to 0.99 mg kg-1 in plants)
      and the reduction of the photosynthetic efficiency of baby spinach. CONCLUSION:
      Low concentrations of ClO2 are effective in reducing the culturable E. coli
      present in irrigation water but it might induce the VBNC state. Presence of
      disinfection by-products and their accumulation in the crop must be considered to
      adjust doses in order to avoid crop damage and chemical safety risks. (c) 2017
      Society of Chemical Industry.

PMID- 29171861
TI  - Matching-adjusted indirect comparison of efficacy in patients with moderate-to
      severe plaque psoriasis treated with ixekizumab vs. secukinumab.
AB  - BACKGROUND: Head-to-head randomized studies comparing ixekizumab and secukinumab
      in the treatment of psoriasis are not available. OBJECTIVES: To assess efficacy
      and quality of life using matching-adjusted indirect comparisons for treatment
      with ixekizumab vs. secukinumab. METHODS: Psoriasis Area and Severity Index
      (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality
      Index (DLQI) 0/1 response rates for approved dosages of ixekizumab (160 mg at
      Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300
      mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared
      using data from active (etanercept and ustekinumab) and placebo-controlled
      studies. Comparisons were made using the Bucher (BU) method and two modified
      versions of the Signorovitch (SG) method (SG total and SG separate).
      Subsequently, results based on active treatment common comparators were combined
      using generic inverse-variance meta-analysis. RESULTS: In the meta-analysis of
      studies with active comparators, PASI 90 response rates were 12.7% [95%
      confidence interval (CI) 5.5-19.8, P = 0.0005], 10.0% (95% CI 2.1-18.0, P = 0.01)
      and 11.2% (95% CI 3.2-19.1, P = 0.006) higher and PASI 100 response rates were
      11.7% (95% CI 5.9-17.5, P < 0.001), 12.7% (95% CI 6.0-19.4, P < 0.001) and 13.1%
      (95% CI 6.3-19.9, P < 0.001) higher for ixekizumab compared with secukinumab
      using BU, SG total and SG separate methods. PASI 75 results were comparable when
      SG methods were used and favoured ixekizumab when the BU method was used. Week 12
      DLQI 0/1 response rates did not differ significantly. CONCLUSIONS: Ixekizumab had
      higher PASI 90 and PASI 100 responses at week 12 compared with secukinumab using
      adjusted indirect comparisons.

PMID- 29171862
TI  - Deployment-Related Military Sexual Trauma Predicts Heavy Drinking and Alcohol
      Problems Among Male Reserve and National Guard Soldiers.
AB  - BACKGROUND: Military sexual trauma (MST) is associated with a range of
      deleterious mental and physical health consequences; however, far less attention
      has been paid to the associations between MST and negative health behaviors, such
      as substance abuse. This study examined 2 focal research questions: (i) What is
      the prevalence of experiencing MST during deployment among male Reserve and
      National Guard soldiers? and (ii) to what extent is the degree of MST exposure
      during deployment associated with frequent heavy drinking and alcohol problems
      postdeployment? METHODS: Data from male soldiers who had been deployed (N = 248)
      were drawn from the baseline wave of Operation: SAFETY (Soldiers And Families
      Excelling Through the Years) an ongoing study examining health among U.S. Army
      Reserve and National Guard and their partners. Participants were recruited over a
      15-month period (Summer 2014 to Fall 2015) from units in New York State.
      Deployments occurred prior to the baseline wave of the study. Analyses examined
      the relation between degree of MST exposure during soldiers' most recent
      deployment and (i) frequent heavy drinking and (ii) alcohol problems, measured at
      baseline, controlling for posttraumatic stress disorder symptoms and age.
      RESULTS: 17.3% of the male service members reported experiencing MST during their
      most recent deployment. Further, greater MST exposure was associated with a
      greater likelihood of engaging in frequent heavy drinking (adjusted risk ratio
      [aRR] = 1.03, 95% CI [1.01, 1.05]) and experiencing alcohol problems (aRR = 1.03,
      95% CI [1.01, 1.06]) at baseline. CONCLUSIONS: Findings demonstrate that MST
      rates are high among male Reserve and National Guard soldiers, and greater MST
      exposure is associated with an increased likelihood of engaging in frequent heavy
      drinking and experiencing alcohol problems among a population already at risk for
      problematic alcohol use.

PMID- 29171864
TI  - Who should receive endoscopic variceal ligation after recovering from acute
      variceal bleeding?

PMID- 29171863
TI  - Schistosoma mansoni-specific immune responses and allergy in Uganda.
AB  - Low allergy-related disease (ARD) prevalence in low-income countries may be
      partly attributed to helminth infections. In the Schistosoma mansoni (Sm)-endemic
      Lake Victoria islands (Uganda), we recently observed positive helminth-allergy
      associations, despite low ARD prevalence. To understand how Sm-induced cytokine
      and antibody profiles might influence allergic response profiles in this
      population, we assessed Schistosoma worm (SWA)- and egg antigen (SEA)-specific
      Th1 (IFN-gamma), Th2 (IL-5, IL-13) and regulatory (IL-10) cytokine profiles (n =
      407), and total (n = 471), SWA-, SEA- and allergen (house dust mite [HDM] and
      cockroach)-specific (as)IgE and IgG4 profiles (n = 2117) by ELISA. Wheeze was
      inversely associated with SWA-specific IFN-gamma (P < .001) and IL-10 (P = .058),
      and SEA-specific IL-5 (P = .004). Conversely, having a detectable asIgE response
      was positively associated with SWA-specific IL-5 (P = .006) and IL-10 (P < .001).
      Total, SWA-, SEA- and allergen-specific IgE and IgG4 responses were higher among
      Sm Kato-Katz positive (SmKK+) and skin prick test (SPT)+ individuals compared to
      SmKK- and SPT- individuals. However, total and asIgG4/IgE ratios were lower among
      SPT+ and wheezing individuals. We conclude that, in this population, helminth
      induced antibody and cytokine responses may underlie individual positive helminth
      atopy associations, while the overall IgG4-IgE balance may contribute to the low
      overall prevalence of clinical allergies in such settings.

PMID- 29171865
TI  - Statins and risk of decompensation in hepatitis B virus-related and hepatitis C
      virus-related cirrhosis: Methodological issues.

PMID- 29171866
TI  - Reply.

PMID- 29171867
TI  - Enthusiastic portrayal of 3D bioprinting in the media: Ethical side effects.
AB  - There has been a surge in mass media reports extolling the potential for using
      three-dimensional printing of biomaterials (3D bioprinting) to treat a wide range
      of clinical conditions. Given that mass media is recognized as one of the most
      important sources of health and medical information for the general public,
      especially prospective patients, we report and discuss the ethical consequences
      of coverage of 3D bioprinting in the media. First, we illustrate how positive
      mass media narratives of a similar biofabricated technology, namely the
      Macchiarini scaffold tracheas, which was involved in lethal experimental human
      trials, influenced potential patient perceptions. Second, we report and analyze
      the positively biased and enthusiastic portrayal of 3D bioprinting in mass media.
      Third, we examine the lack of regulation and absence of discussion about risks
      associated with bioprinting technology. Fourth, we explore how media
      misunderstanding is dangerously misleading the narrative about the technology.

PMID- 29171868
TI  - Efficient quantification of water content in edible oils by headspace gas
      chromatography with vapour phase calibration.
AB  - BACKGROUND: An automated and accurate headspace gas chromatographic (HS-GC)
      technique was investigated for rapidly quantifying water content in edible oils.
      In this method, multiple headspace extraction (MHE) procedures were used to
      analyse the integrated water content from the edible oil sample. A simple vapour
      phase calibration technique with an external vapour standard was used to
      calibrate both the water content in the gas phase and the total weight of water
      in edible oil sample. After that the water in edible oils can be quantified.
      RESULTS: The data showed that the relative standard deviation of the present HS
      GC method in the precision test was less than 1.13%, the relative differences
      between the new method and a reference method (i.e. the oven-drying method) were
      no more than 1.62%. CONCLUSION: The present HS-GC method is automated, accurate,
      efficient, and can be a reliable tool for quantifying water content in edible oil
      related products and research. (c) 2017 Society of Chemical Industry.

PMID- 29171869
TI  - Disinfection by-products in baby lettuce irrigated with electrolysed water.
AB  - BACKGROUND: Irrigation water disinfection reduces the microbial load but it might
      lead to the formation and accumulation of disinfection by-products (DBPs) in the
      crop. If DBPs are present in the irrigation water, they can accumulate in the
      crop, particularly after the regrowth, and be affected by the postharvest
      handling such as washing and storage. To evaluate the potential accumulation of
      DBPs, baby lettuce was grown using irrigation water treated with electrolysed
      water (EW) in a commercial greenhouse over three consecutive harvests and
      regrowths. The impact of postharvest practices such as washing and storage on DBP
      content was also assessed. RESULTS: Use of EW caused the accumulation of
      chlorates in irrigation water (0.02-0.14 mg L-1 ), and in the fresh produce (0.05
      0.10 mg kg-1 ). On the other hand, the disinfection treatment had minor impact
      regarding the presence of trihalomethanes (THMs) in water (0.3-8.7 MUg L-1 max),
      and in baby lettuce (0.3-2.9 MUg kg-1 max). CONCLUSIONS: Disinfection of
      irrigation water with EW caused the accumulation of chlorates in the crop
      reaching levels higher than the current maximum residual limit established in the
      EU legislation for leafy greens. (c) 2017 Society of Chemical Industry.

PMID- 29171870
TI  - Modulation of O2 reduction in Saccharomyces cerevisiae mitochondria.
AB  - Respiratory supercomplex factor (Rcf) 1 is a membrane-bound protein that
      modulates the activity of cytochrome c oxidase (CytcO) in Saccharomyces
      cerevisiae mitochondria. To investigate this regulatory mechanism, we studied the
      interactions of CytcO with potassium cyanide (KCN) upon removal of Rcf1. While
      the addition of KCN to the wild-type mitochondria results in a full reduction of
      heme a, with the rcf1Delta mitochondria, a significant fraction remains oxidized.
      Upon addition of ascorbate in the presence of O2 and KCN, the reduction level of
      hemes a and b was a factor of ~ 2 larger with the wild-type than with the
      rcf1Delta mitochondria. These data indicate that turnover of CytcO was less
      blocked in rcf1Delta than in the wild-type mitochondria, suggesting that Rcf1
      modulates the structure of the catalytic site.

PMID- 29171872
TI  - Topological characterization of the mitochondrial phospholipid scramblase 3.
AB  - Scramblases redistribute phospholipids in biological membranes. Phospholipid
      scramblase 3 (PLSCR3), which is located in mitochondria, has been reported to be
      involved in cardiolipin distribution from the inner to the outer membrane, thus
      regulating cellular processes such as apoptosis or mitophagy. However, the
      localization and topology of this protein has not been convincingly addressed to
      support a role in intermembrane phospholipid transfer. Here, we studied PLSCR3
      topology within mitochondria. We show that PLSCR3 inserts in the inner membrane
      (IM) via its C-terminal transmembrane helix, whereas its N-terminal portion is
      oriented toward the intermembrane space where it is activated by calcium. Our
      results suggest that PLSCR3, via its C-terminal transmembrane domain,
      participates in the bidirectional movement of phospholipids within the IM.

PMID- 29171871
TI  - Cytokine responses, microbial aetiology and short-term outcome in community
      acquired pneumonia.
AB  - BACKGROUND: The inflammatory response to community-acquired pneumonia (CAP) is
      orchestrated through activation of cytokine networks and the complement system.
      We examined the association of multiple cytokines and the terminal complement
      complex (TCC) with microbial aetiology, disease severity and short-term outcome.
      MATERIALS AND METHODS: Plasma levels of 27 cytokines and TCC were analysed in
      blood samples obtained at hospital admission, clinical stabilization and 6-week
      follow-up from 247 hospitalized adults with CAP. Fourteen mediators were included
      in final analyses. Adverse short-term outcome was defined as intensive care unit
      (ICU) admission and 30-day mortality. RESULTS: Cytokine and TCC levels were
      dynamic in the clinical course of CAP, with highest levels seen at admission for
      most mediators. Admission levels of cytokines and TCC did not differ between
      groups of microbial aetiology. High admission levels of IL-6 (odds ratio [OR]
      1.47, 95% confidence interval [CI] 1.18-1.84, P = .001), IL-8 (OR 1.79, 95% CI
      1.26-2.55, P = .001) and MIP-1beta (OR 2.28, 95% CI 1.36-3.81, P = .002) were
      associated with a CURB-65 severity score of >=3, while IL-6 (OR 1.37, 95% CI 1.07
      1.74, P = .011) and MIP-1beta (OR 1.86, 95% CI 1.03-3.36, P = .040) were
      associated with a high risk of an adverse short-term outcome. CONCLUSIONS: In
      this CAP cohort, admission levels of IL-6, IL-8 and MIP-1beta were associated
      with disease severity and/or adverse short-term outcome. Still, for most
      mediators, only nonsignificant variations in inflammatory responses were observed
      for groups of microbial aetiology, disease severity and short-term outcome.

PMID- 29171873
TI  - Let it go: Relationship autonomy predicts pro-relationship responses to partner
      transgressions.
AB  - OBJECTIVE: The purpose of the present research is to better understand how
      relationship autonomy-having more self-determined reasons for being committed to
      a relationship-contributes to pro-relationship responses to transgressions in
      romantic relationships (e.g., forgiveness and accommodation). METHOD: Study 1
      employed a cross-sectional design (N = 350) and Study 2 used a weekly diary (N =
      121) to test associations between relationship autonomy and pro-relationship
      responses to transgressions. Studies 3 and 4 utilized dyadic designs (Study 3: N
      = 200 couples, 400 individuals; Study 4: N = 275 couples, 550 individuals) to
      determine how both partners' relationship autonomy is associated with pro
      relationship responses. RESULTS: Results revealed that relationship autonomy is
      robustly associated with pro-relationship responses to transgressions, both as
      general tendencies and as responses to idiosyncratic transgressions. Results of
      actor-partner interdependence model (APIM) analyses in Studies 3 and 4 provide
      evidence that one's partner's relationship autonomy is important for promoting
      pro-relationship responses as well. Study 4 also found that people perceive that
      partners respond better to transgressions if their partner is high in
      relationship autonomy. CONCLUSIONS: This research provides consistent and
      compelling evidence that the degree of self-determination underlying commitment
      is important for understanding how people respond to transgressions in their
      relationships, beyond their current levels of commitment.

PMID- 29171874
TI  - Serum paraoxonase-1 activity is inversely related to free thyroxine in euthyroid
      subjects: The PREVEND Cohort Study.
AB  - BACKGROUND: Low-normal thyroid function within the euthyroid range has been
      suggested to enhance atherosclerosis susceptibility. Paraoxonase-1 (PON-1) may
      protect against atherosclerotic cardiovascular disease development by attenuating
      oxidative stress. We evaluated relationships of PON-1 with thyroid stimulating
      hormone (TSH), free T4 , free T3 , lipids and apolipoprotein (apo)A-I in
      euthyroid subjects, and assessed whether such relationships are modified in the
      context of the metabolic syndrome (MetS). MATERIALS AND METHODS: Serum PON-1
      activity (arylesterase activity), TSH, free T4 , free T3 , lipids and apoA-I was
      measured in 2206 euthyroid subjects (aged 28-75 years; 1138 men (age 49 +/- 13
      years) and 1068 women (age 46 +/- 12 years), recruited from the general
      population (PREVEND cohort). RESULTS: In age- and sex-adjusted analysis, PON-1
      activity (divided into tertiles) was positively related to TSH (beta = -0.045, P
      = .036) and inversely to free T4 (beta = -0.042, P = .050) but not to free T3
      (beta = -0.027, P = .20). PON-1 activity was positively related to total
      cholesterol, non-HDL cholesterol and triglycerides, as well as to HDL cholesterol
      and apoA-I (P < .01 to <.001). The inverse relationship of PON-1 activity with
      free T4 remained present after adjustment for lipids and other potential
      confounders (beta = -0.066, P = .002), but the positive relationship with TSH
      lost significance (beta = 0.034, P = .11). The inverse relationship of PON-1
      activity with free T4 was not different in subjects with vs without MetS (P =
      .94), nor modified by the presence of its individual components (P >= .22 for
      each). CONCLUSIONS: Serum PON-1 activity is inversely associated with free T4 in
      euthyroid subjects, suggesting that low-normal thyroid function may affect PON-1
      regulation.

PMID- 29171875
TI  - Transcriptomic analysis on responses of the liver and kidney of finishing pigs
      fed cadmium contaminated rice.
AB  - BACKGROUND: Cadmium (Cd) is a common harmful substance that has many deleterious
      effects on the liver and kidney. Most reports about Cd toxic studies focused on
      its inorganic status, whereas the toxicity of Cd in organic materials is less
      studied. Here, we performed RNA-seq to explore the influences of Cd contaminated
      rice on function of the liver and kidney of finishing pigs. RESULTS: The
      concentration of Cd in liver and kidney of pigs fed Cd contaminated rice
      increased by 4.00 and 2.94 times, respectively, compared to those in the control
      group. With transcriptomic analysis, approximately 4-6 * 107 clean reads were
      acquired. Five differently expressed genes (DEGs) were identified in the liver,
      and 12 DEGs in the kidney. SPHK2 was commonly down-regulated. No significantly
      enriched gene ontology (GO) terms were identified. By Kyoto encyclopaedia of
      genes and genomes (KEGG) enrichments, four pathways were identified in hepatic
      tissue, and five pathways in nephritic tissue. Intriguingly, two pathways
      (sphingolipid metabolism and VEGF signalling pathway) were altered both in the
      liver and kidney. CONCLUSION: Cd contaminated rice may cause liver and kidney
      damage and inflammation, or even lead to more severe harm to these tissues. (c)
      2017 Society of Chemical Industry.

PMID- 29171876
TI  - Decreased platelet inhibition by P2Y12 receptor blockers in anaemia.
AB  - BACKGROUND: Anaemic patients undergoing angioplasty and stenting are at an
      increased risk of ischaemic events, which may be caused by an inadequate response
      to antiplatelet therapy with adenosine diphosphate (ADP) P2Y12 inhibitors. In the
      current study, we investigated the associations between anaemia and on-treatment
      platelet reactivity in clopidogrel-treated (group 1, n = 306) and prasugrel
      /ticagrelor-treated (group 2, n = 109) patients undergoing elective and acute
      angioplasty with stent implantation, respectively. MATERIALS AND METHODS:
      Monocyte-platelet aggregate (MPA) formation was determined by flow cytometry in
      both groups. On-treatment residual platelet reactivity in response to ADP was
      assessed by light transmission aggregometry (LTA) in both groups, and by the
      VerifyNow P2Y12 assay and the Impact-R in group 1. P-selectin expression was
      measured by flow cytometry in group 2. RESULTS: In both groups, anaemia was
      associated with significantly higher MPA formation in response to ADP (both P <=
      .02). Moreover, by LTA maximal aggregation in response to ADP was significantly
      higher in patients with anaemia in both groups (both P < .05), and anaemic
      patients in group 1 had a significantly higher on-treatment platelet reactivity
      by the VerifyNow P2Y12 assay and the Impact-R than those without anaemia (both P
      < .001). In group 2, significantly higher platelet surface expression of P
      selectin was seen in anaemia after stimulation with ADP (P = .02). CONCLUSION:
      Anaemia is associated with decreased platelet inhibition by ADP P2Y12 receptor
      antagonists after elective and acute percutaneous interventions with stent
      implantation. However, due to inconsistencies between different platelet function
      tests additional data are needed to clarify the role of anaemia for platelet
      inhibition.

PMID- 29171877
TI  - Personality traits and maladaptivity: Unipolarity versus bipolarity.
AB  - OBJECTIVE: Dimensional personality trait models have gained favor as an
      alternative to categorical personality disorder (PD) diagnosis; however, debate
      persists regarding whether these traits should be conceptualized as maladaptive
      at both extremes (i.e., maladaptively bipolar) or just one trait pole (i.e.,
      unipolar). METHOD: To inform the debate on maladaptive bipolarity, linear and
      nonlinear relations between personality traits and dysfunction were examined in a
      large psychiatric patient sample (N = 365). Participants self-reported on normal
      range and pathological personality domains, life satisfaction, specific
      interpersonal problems, and broad psychosocial functioning. In addition,
      participants were interviewed regarding specific psychiatric symptoms and broad
      psychosocial functioning. RESULTS: All traits related moderately to strongly with
      at least one dysfunction variable. All traits were predominantly correlated with
      dysfunction at one pole; however, several small linear relations provided some
      evidence for maladaptively high Extraversion and Agreeableness. None of the
      significant nonlinear effects provided clear evidence for maladaptivity at both
      ends of any trait. CONCLUSIONS: Taken together, these results suggest that broad
      personality traits are predominantly maladaptive at one extreme; however, in
      limited cases, the opposite extreme may also be maladaptive.

PMID- 29171878
TI  - Tophus size is associated with hallux valgus deformity in gout.
AB  - OBJECTIVE: Hallux valgus (HV) and gout are common pathologies of the first
      metatarsophalangeal joint (MTP1) leading to pain and deformation. In this study,
      we aimed to determine the correlation between tophus size and characteristics of
      HV in gouty patients. METHODS: In this case-control study, we included patients
      with gout (the presence of monosodium urate crystals in synovial fluid) and
      control patients with spondyloarthritis, without crystal disease disorders.
      Radiographic assessment and ultrasound (US) assessment were performed by two
      blinded operators. US features of gout (double contour [DC] sign and/or tophus)
      were collected. HV was defined by hallux abductus (HA) angle >=20 degrees  and/or
      intermetatarsal angle (IM) >=10 degrees . Correlation between US findings and HV
      angles was estimated by Spearman correlation coefficient. RESULTS: We included 56
      gouty patients (87.5% males, mean age of 63.9 +/- 12.2 years) and 41 control
      patients (90% males, mean age of 59.0 +/- 12.8 years). HV was more frequent in
      patients with gout than controls (62% vs 37%, P = .0007). Regardless of HV
      status, correlations were found between the size of US tophi and IM (r = .3381, P
      = .003) and HA angles (r = .2344, P = .043). CONCLUSIONS: Our results confirm a
      high prevalence of HV in gouty patients. We also observed a correlation between
      the size of the US tophus and the angles defining HV, which suggests a link
      between urate deposition load and HV. Early urate-lowering therapy for gout could
      limit the occurrence of HV.

PMID- 29171879
TI  - Bidirectional associations between emotions and school adjustment.
AB  - OBJECTIVE: We examined the relations of children's (N = 301) observed expression
      of negative and positive emotion in classes or nonclassroom school contexts
      (i.e., lunch and recess) to school adjustment from kindergarten to first grade.
      METHOD: Naturalistic observations of children's emotional expressivity were
      collected, as were teachers' reports of children's school engagement and
      relationship quality with teachers and peers. RESULTS: In longitudinal panel
      models, greater teacher-student conflict and lower student engagement in
      kindergarten predicted greater negative expressivity in both school contexts.
      School engagement and peer acceptance in kindergarten positively predicted first
      grade positive emotion in the classroom. Suggestive of possible bidirectional
      relations, there was also small unique prediction (near significant) from
      negative expressivity at lunch and recess to higher teacher-student conflict,
      from negative expressivity in the classroom to low peer acceptance, and from
      positive expressivity in the classroom to higher peer acceptance. CONCLUSIONS:
      The pattern of findings suggests that the quality of experience at school
      uniquely predicts children's emotional expressivity at school more consistently
      than vice versa-a finding that highlights the important role of school context in
      young children's emotionality at school.

PMID- 29171880
TI  - Torsional fatigue resistance of pathfinding instruments manufactured from several
      nickel-titanium alloys.
AB  - AIM: To evaluate the torsional properties of pathfinding nickel-titanium (NiTi)
      rotary instruments manufactured from several NiTi alloys, ProGlider (M-wire),
      Hyflex GPF (conventional NiTi Wire and controlled memory wire), Logic
      (conventional NiTi wire and controlled memory wire) and Mtwo (conventional NiTi
      wire). METHODOLOGY: A total of 56 NiTi instruments from Glidepath rotary systems
      (n = 8) were used: Logic (size 25, .01 taper), Logic CM (size 25, .01 taper),
      ProGlider (size 16, .02 taper), Hyflex GPF (size 15, .01 taper), Hyflex GPF CM
      (size 15, .02 taper; size 20, .02 taper) and Mtwo (size 10, .04 taper). The
      torsion tests were performed based on ISO 3630-1 (1992). Three millimetres of
      each instrument tip was clamped to a small load cell by a lever arm linked to the
      torsion axis. Data were analysed using a one-way analysis of variance (anova) and
      Tukey test with a significance level at a = 5%. RESULTS: The Logic size 25, .01
      taper had significantly higher torsional strength values (P < 0.05). The
      ProGlider was significantly different when compared with Hyflex GPF size 15, .01
      taper and size 15, .02 taper (P < 0.05). The Logic CM size 25, .01 taper had
      significantly higher torsional strength than Hyflex GPF size 15, .01 taper and
      size 15, .02 taper (P < 0.05). No difference was found amongst Mtwo size 10, .04
      taper and Hyflex GPF groups (size 15, .01 taper; size 15, .02 taper; size 20, .02
      taper). In relation to the angle of rotation, Logic CM size 25, .01 taper and
      Hyflex GPF size 15, .01 taper had the highest angle values (P < 0.05). The
      ProGlider had the lowest angle values in comparison with all the groups (P <
      0.05) followed by Mtwo size 10, .04 taper. The Logic size 25, .01 taper had
      significantly higher angle of rotation values than ProGlider and Mtwo size 10,
      .04 taper (P < 0.05). CONCLUSION: The Logic size 25, .01 taper instrument made of
      conventional NiTi alloy had the highest torsional strength of all instruments
      tested. In addition, the ProGlider instrument manufactured from M-Wire alloy had
      the lowest angle of rotation to fracture in comparison with the other
      instruments.

PMID- 29171881
TI  - RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression
      through YTHDF2-dependent posttranscriptional silencing of SOCS2.
AB  - : Epigenetic alterations have contributed greatly to human carcinogenesis.
      Conventional epigenetic studies have predominantly focused on DNA methylation,
      histone modifications, and chromatin remodeling. Recently, diverse and reversible
      chemical modifications of RNAs have emerged as a new layer of epigenetic
      regulation. N6-methyladenosine (m6A) is the most abundant chemical modification
      of eukaryotic messenger RNA (mRNA) and is important for the regulation of mRNA
      stability, splicing, and translation. Using transcriptome sequencing, we
      discovered that methyltransferase-like 3 (METTL3), a major RNA N6-adenosine
      methyltransferase, was significantly up-regulated in human hepatocellular
      carcinoma (HCC) and multiple solid tumors. Clinically, overexpression of METTL3
      is associated with poor prognosis of patients with HCC. Functionally, we proved
      that knockdown of METTL3 drastically reduced HCC cell proliferation, migration,
      and colony formation in vitro. Knockout of METTL3 remarkably suppressed HCC
      tumorigenicity and lung metastasis in vivo. On the other hand, using the
      CRISPR/dCas9-VP64 activation system, we demonstrated that overexpression of
      METTL3 significantly promoted HCC growth both in vitro and in vivo. Through
      transcriptome sequencing, m6A sequencing, and m6A methylated RNA immuno
      precipitation quantitative reverse-transcription polymerase chain reaction, we
      identified suppressor of cytokine signaling 2 (SOCS2) as a target of METTL3
      mediated m6A modification. Knockdown of METTL3 substantially abolished SOCS2 mRNA
      m6A modification and augmented SOCS2 mRNA expression. We also showed that m6A
      mediated SOCS2 mRNA degradation relied on the m6A reader protein YTHDF2-dependent
      pathway. CONCLUSION: METTL3 is frequently up-regulated in human HCC and
      contributes to HCC progression. METTL3 represses SOCS2 expression in HCC through
      an m6A-YTHDF2-dependent mechanism. Our findings suggest an important mechanism of
      epigenetic alteration in liver carcinogenesis. (Hepatology 2018;67:2254-2270).

PMID- 29171882
TI  - Characterization of epitope specificities of reference antibodies used for the
      quantification of the birch pollen allergen Bet v 1.
AB  - BACKGROUND: Accurate allergen quantification is needed to document the
      consistency of allergen extracts used for immunotherapy. Herein, we characterize
      the epitope specificities of two monoclonal antibodies used in an ELISA for the
      quantification of the major birch pollen allergen Bet v 1, established as a
      reference by the BSP090 European project. METHODS: The ability of mAbs 5B4 and
      6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography. The
      capacity of each mAb to compete with patients' IgE for binding to Bet v 1 was
      measured by ELISA inhibition. Epitope mapping was performed by pepscan analysis,
      site-directed mutagenesis, and hydrogen/deuterium exchange-mass spectrometry.
      RESULTS: The 5B4 epitope corresponds to a peptide sequence (I56-K68) overlapping
      with the binding sites of patients' serum IgEs. Mutation of residues P59, E60,
      and K65 abolishes 5B4 binding to Bet v 1 and reduces the level of IgE
      recognition. In contrast, 6H4 recognizes a conformational epitope lying opposite
      to the 5B4 binding site, involving residues located in segments I44-K55 and R70
      F79. Substitution of E45 reduces the binding capacity of 6H4, confirming that it
      is critical for the interaction. Both mAbs interact with >90% of Bet v 1 content
      present in the birch pollen extract, while displaying a weak cross-reactivity
      with other allergens of the PR-10 family. CONCLUSIONS: MAbs 5B4 and 6H4 recognize
      structurally distinct epitopes present in the vast majority of Bet v 1 isoforms.
      These results support the relevance as a reference method of the Bet v 1-specific
      quantitative ELISA adopted by the European Pharmacopoeia.

PMID- 29171883
TI  - A Call for Empirical Research on Uterine Transplantation and Reproductive
      Autonomy.
AB  - Uterine transplantation could give women who suffer from uterine factor
      infertility the possibility of experiencing gestation. Much of the ethical
      discussion about uterine transplantation has focused on whether research on it
      should even be pursued, but researchers are nevertheless moving forward with
      several uterine transplant research protocols. Scholars should therefore already
      be identifying and engaging in an intimate examination of the ethical realities
      of offering uterine transplantation in a clinical setting. Given the potential
      for the procedure to expand reproductive options for women, reproductive autonomy
      has been a primary principle underlying much of the ethical discourse about the
      hypothetical impact of uterine transplantation. Yet the factors that will affect
      whether uterine transplants promote or undermine a patients' reproductive
      autonomy if the procedure is integrated into clinical practice have yet to be
      rigorously explored. Focusing on the clinical realities of patient autonomy, I
      argue that empirical data exploring prospective recipients' motivations and their
      perceptions of the benefits of the procedure in the context of their lived
      experiences are critical to a robust analysis of the ethical dimensions of
      uterine transplantation.

PMID- 29171884
TI  - Autonomy in Tension: Reproduction, Technology, and Justice.
AB  - Respect for autonomy is a central value in reproductive ethics, but it can be a
      challenge to fulfill and is sometimes an outright puzzle to understand. If a
      woman requests the transfer of two, three, or four embryos during fertility
      treatment, is that request truly autonomous, and do clinicians disrespect her if
      they question that decision or refuse to carry it out? Add a commitment to
      justice to the mix, and the challenge can become more complex still. Is it unfair
      for insurance policies to exclude from coverage the costs of giving fertility to
      those who lack it or restoring fertility in those who have lost it? What does
      "just reproduction" look like in the face of multifarious understandings of both
      justice and autonomy and in light of increasingly complex and costly reproductive
      technologies? In today's dialogue about reproduction, medicine, and ethics in the
      United States, old ethical issues-such as whether women ought to be allowed to
      access pregnancy termination-are more contested than they have been in decades,
      while new technologies-like those used to edit the genes of human embryos-suggest
      that our species could face unprecedented questions about who should exist. As we
      considered the discussions accompanying these issues and contemplated a special
      report responding to them, we found ourselves consistently circling back to two
      ethical commitments: respect for autonomy and the pursuit of justice. As one of
      the nine essays in this collection asks, why should certain women receive help to
      establish a pregnancy while others are thrown in jail when they miscarry or their
      child is stillborn? Respect for autonomy is required where individuals have the
      ability to make fully informed and voluntary choices. Yet does respecting
      autonomy require acceding to all the choices of patients or consumers of medical
      care? We consider these and related questions in this special report from the
      Hastings Center Report.

PMID- 29171885
TI  - About The Hastings Center.

PMID- 29171886
TI  - Reproductive Rights without Resources or Recourse.
AB  - The U.S. Supreme Court declared procreation to be a fundamental right in the
      early twentieth century in a case involving Oklahoma's Habitual Criminal
      Sterilization Act, an act that permitted unconsented sterilization of individuals
      convicted of certain crimes. The right that the Court articulated in that case is
      a negative right: it requires that the government not place unjustified
      roadblocks in the way of people seeking to procreate, but it does not require the
      government to take positive steps to help people procreate if they wish to. I
      argue that a positive legal right is morally necessary in the United States,
      given the profound significance of procreation, the current barriers to access to
      care, and the related issues of individual and societal justice. I assume at the
      outset that the right to procreate should be expansive enough to include a right
      to noncoital reproduction. The absence of a positive right to procreate reflects
      not just constitutional tradition but also a governmental and societal commitment
      to a longstanding set of reproductive hierarchies by which those who fall outside
      of the traditional framing of family too frequently find their procreative dreams
      hindered. Reconceiving procreative rights to include a positive right would
      create greater opportunities to argue and lobby for increased access to
      technologies that are out of reach for many.

PMID- 29171887
TI  - Freezing Eggs and Creating Patients: Moral Risks of Commercialized Fertility.
AB  - There's no doubt that reproductive technologies can transform lives for the
      better. Infertile couples and single, lesbian, gay, intersex, and transgender
      people have the potential to form families in ways that would have been
      inconceivable years ago. Yet we are concerned about the widespread
      commercialization of certain egg-freezing programs, the messages they propagate
      about motherhood, the way they blur the line between care and experimentation,
      and the manipulative and exaggerated marketing that stretches the truth and
      inspires false hope in women of various ages. We argue that although reproductive
      technology, and egg freezing in particular, promise to improve women's care by
      offering more choices to achieve pregnancy and childbearing, they actually have
      the potential to be disempowering. First, commercial motives in the fertility
      industry distort women's medical deliberations, thereby restricting their
      autonomy; second, having the option to freeze their eggs can change the meaning
      of women's reproductive choices in a way that is limiting rather than liberating.

PMID- 29171889
TI  - The Shifting Landscape of Prenatal Testing: Between Reproductive Autonomy and
      Public Health.
AB  - Since the 1970s, prenatal testing has been integrated into many health care
      systems on the basis of two competing and largely irreconcilable rationales. The
      reproductive autonomy rationale focuses on nondirective counseling and consent as
      ways to ensure that women's decisions about testing and subsequent care are
      informed and free of undue pressures. It also represents an easily understandable
      and ethically convincing basis for widespread access to prenatal testing, since
      the value of autonomy is well established in Western bioethics and widely
      recognized by funders of health care. In contrast, the public health rationale
      approaches prenatal testing as designed to reduce the incidence of certain
      conditions in the population to reduce the burden of disease. This rationale
      emphasizes the societal consequences of reproduction and the aggregate impact of
      women's individual reproductive decisions on the overall health of future
      populations. In this essay, I argue that, despite what could be seen as a
      persistent failure to meet the ideals of reproductive autonomy, resisting the
      public health rationale as a basis for prenatal screening is ethically and
      pragmatically crucial. I recommend policy mechanisms that can enhance
      reproductive autonomy at a societal level to support choice at the individual
      level.

PMID- 29171890
TI  - Reproductive Autonomy and Regulation-Coexistence in Action.
AB  - On occasion, British in vitro fertilization practitioners look over the ocean to
      the practice of IVF and embryo research in the United States, wonder why these
      areas are subject to less regulation than in the United Kingdom, and ask how much
      less risky and more progressive IVF and embryo research might be if subject to
      additional federal, or at least state, regulation. To an American audience,
      imbued with the centuries-old spirit of independence, regulation and autonomy can
      seem in tension. From a British perspective, there is no necessary conflict.
      There is no dissent in the United Kingdom from the proposition that individual
      activities, services, and industries can be regulated and, at the same time,
      retain and exercise such autonomy as is their right within a safe sphere. From
      1994 to 2002, I was the chair of the United Kingdom's Human Fertilisation and
      Embryology Authority, which regulates the practice of IVF and embryo research.
      The existence of the HFEA assures patients that safety and aspects of the
      practice of assisted reproduction are monitored, leaving them free to choose
      without worrying about danger, in the same way that the public may take only
      those drugs that have passed health and safety tests. I would propose that
      anxious and vulnerable patients do not have more autonomy in a less regulated,
      market-driven field.

PMID- 29171891
TI  - About the Special Report.

PMID- 29171892
TI  - Parenting in the Age of Preimplantation Gene Editing.
AB  - Medical science at its core aims to preserve health and eliminate disease, but a
      common theme in scientific discovery is the application of findings in ways that
      were not the primary intent. The development of diagnostic modalities to predict
      the health of resulting children has been a fundamental aim underpinning research
      into prenatal and preimplantation diagnostic modalities; however, the knowledge
      gained has in some cases been utilized for nonmedical purposes. As an example,
      amniocentesis developed to determine whether the pregnancy is chromosomally
      normal also provides information about the sex of the fetus, which normally does
      not affect health. The emerging gene-editing technologies that could be used to
      repair mutated disease-causing genes in an embryo will presumably also be able to
      be used to alter traits unrelated to disease. And yet, I will argue, the desire
      to preserve the mystery of reproduction remains a central value in humans' quest
      to reproduce. This yearning to maintain the mysteries will likely temper the
      development of strategies to alter our genome and affect the genetic identities
      of our offspring. In my experience as an obstetrician and reproductive
      endocrinology and infertility subspecialist, people want to have, not the best
      possible baby, but rather their own baby.

PMID- 29171893
TI  - Should Clinicians Set Limits on Reproductive Autonomy?
AB  - As a gynecologic surgeon with a focus on infertility, I frequently hold complex
      discussions with patients, exploring with them the risks and benefits of surgical
      options. In the past, we physicians may have expected our patients to simply
      defer to our expertise and choose from the options we presented. In our
      contemporary era, however, patients frequently request options not favored by
      their physicians and even some they've found themselves online. In reproductive
      endocrinology and infertility, the range of options that may be offered or that
      patients may themselves seek out is continuously widening. Physicians certainly
      seek to find the option that will result in the best outcome for their patients,
      but the information to guide us in achieving the best outcome can be vague or
      conflicting. Add to this the financial and emotional pressures bearing on
      patients seeking assisted reproduction. In this essay, I explore the extent to
      which clinicians in reproductive medicine should follow patient requests with
      which they disagree or instead try to persuade the patient to do something else
      or simply refuse outright to meet the request. And if persuasion is to be used,
      what would be legitimate methods? Clearly, coercion is unacceptable, but the line
      between persuasion and coercion can be elusive. At what point can or should
      clinicians resist such requests-and to what degree?

PMID- 29171894
TI  - The Future of Reproductive Autonomy.
AB  - In a project The Hastings Center is now running on the future of prenatal
      testing, we are encountering clear examples, both in established law and in the
      practices of individual providers, of failures to respect women's reproductive
      autonomy: when testing is not offered to certain demographics of women, for
      instance, or when the choices of women to terminate or continue pregnancies are
      prohibited or otherwise not supported. But this project also raises puzzles for
      reproductive autonomy. We have learned that some clinicians and patients do not
      discuss the fact that prenatal testing can lead to a decision about whether to
      terminate a pregnancy-they just don't talk about it. And while the decision
      whether to agree to prenatal screening and diagnostic testing is to be made with
      women's free and informed consent, many screening tests have been routinized in
      such a way that some women do not even recall agreeing to testing, while others
      feel that agreeing to testing is what their clinicians expect of them or that the
      testing is necessary to protect themselves and their families from the
      significant financial hardship of raising a child with a disability. In the face
      of these pressures, can one really say that women are freely choosing to undergo
      testing or are freely choosing to continue or terminate a pregnancy following
      receipt of test results? The reality of these pressures is requiring us to
      consider expanding the scope of our investigation beyond the clinical encounter
      to the broader context-to think harder about what reproductive autonomy means and
      how best to enhance it.

PMID- 29171895
TI  - How the Criminalization of Pregnancy Robs Women of Reproductive Autonomy.
AB  - In 2003, the South Carolina Supreme Court upheld the conviction of Regina
      McKnight, an African American woman who was convicted at the age of twenty-two
      for committing "homicide by child abuse." She became the first woman in the
      United States to be arrested, prosecuted, and convicted for experiencing a
      stillbirth. Rather than an outlier case in the annals of American jurisprudence
      that stretched law beyond reason while restraining compassion and justice,
      McKnight's conviction inspired similar prosecutions of other poor black women and
      then of other women. More than one-third of states consider pregnant women's
      illicit drug use a form of child abuse, resulting in unprecedented forms of
      criminal and civil punishment. Laws previously understood to protect pregnant
      women from domestic violence during pregnancy, such as fetal protection laws, now
      serve as the vehicles for prosecuting pregnant women. What these prosecutions and
      laws expose are the multitudinous ways in which the criminalization of poor
      pregnant women-and normalization of that criminalization, such that even doctors
      and nurses are expected to participate in it-serve to humiliate women, interfere
      with their reproductive health, and ultimately rob women of reproductive
      autonomy.

PMID- 29171896
TI  - A protocol for combining fluorescent proteins with histological stains for
      diverse cell wall components.
AB  - Higher plant function is contingent upon the complex three-dimensional (3D)
      architecture of plant tissues, yet severe light scattering renders deep, 3D
      tissue imaging very problematic. Although efforts to 'clear' tissues have been
      ongoing for over a century, many innovations have been made in recent years.
      Among them, a protocol called ClearSee efficiently clears tissues and diminishes
      chlorophyll autofluorescence while maintaining fluorescent proteins - thereby
      allowing analysis of gene expression and protein localisation in cleared samples.
      To further increase the usefulness of this protocol, we have developed a ClearSee
      based toolbox in which a number of classical histological stains for lignin,
      suberin and other cell wall components can be used in conjunction with
      fluorescent reporter lines. We found that a number of classical dyes are highly
      soluble in ClearSee solution, allowing the old staining protocols to be
      enormously simplified; these additionally have been unsuitable for co
      visualisation with fluorescent markers due to harsh fixation and clearing.
      Consecutive staining with several dyes allows 3D co-visualisation of distinct
      cell wall modifications with fluorescent proteins - used as transcriptional
      reporters or protein localisation tools - deep within tissues. Moreover, the
      protocol is easily applied on hand sections of different organs. In combination
      with confocal microscopy, this improves image quality while decreasing the time
      and cost of embedding/sectioning. It thus provides a low-cost, efficient method
      for studying thick plant tissues which are usually cumbersome to visualise. Our
      ClearSee-adapted protocols significantly improve and speed up anatomical and
      developmental investigations in numerous plant species, and we hope they will
      contribute to new discoveries in many areas of plant research.

PMID- 29171897
TI  - Structural whole-brain covariance of the anterior and posterior hippocampus:
      Associations with age and memory.
AB  - The hippocampus (HC) interacts with distributed brain regions to support memory
      and shows significant volume reductions in aging, but little is known about age
      effects on hippocampal whole-brain structural covariance. It is also unclear
      whether the anterior and posterior HC show similar or distinct patterns of whole
      brain covariance and to what extent these are related to memory functions
      organized along the hippocampal longitudinal axis. Using the multivariate
      approach partial least squares, we assessed structural whole-brain covariance of
      the HC in addition to regional volume, in young, middle-aged and older adults (n
      = 221), and assessed associations with episodic and spatial memory. Based on
      findings of sex differences in both memory and brain aging, we further considered
      sex as a potential modulating factor of age effects. There were two main
      covariance patterns: one capturing common anterior and posterior covariance, and
      one differentiating the two regions by capturing anterior-specific covariance
      only. These patterns were differentially related to associative memory while
      unrelated to measures of single-item memory and spatial memory. Although patterns
      were qualitatively comparable across age groups, participants' expression of both
      patterns decreased with age, independently of sex. The results suggest that the
      organization of hippocampal structural whole-brain covariance remains stable
      across age, but that the integrity of these networks decreases as the brain
      undergoes age-related alterations.

PMID- 29171898
TI  - I had no other option: Women, electroconvulsive therapy, and informed consent.
AB  - Electroconvulsive therapy (ECT) is a controversial procedure used in the
      management of depression. Whilst it may be administered under mental health
      legislation, it is usually given to people who voluntarily consent. At the
      practice level, the consent process for ECT requires a detailed explanation of
      the procedure. The person consenting must have capacity to make this decision,
      and consent must be given freely and without coercion. Research using a feminist
      narrative approach unexpectedly highlighted the issue of potential coercion in
      the context of explaining the procedure. In-depth interviews were used to
      understand seven women's accounts of deciding to receive ECT. A thematic analysis
      of their narratives uncovered a shared concern with how they consented to the
      treatment. Four subthemes were identified that related to the way in which they
      provided their consent: (i) 'Not enough information'; (ii) 'I had no other
      choice'; (iii) 'Just go along with it'; and (iv) 'Lacking capacity'. A consent
      process that includes elements of passive coercion and a lack of timely and
      appropriate information influences the way some women make decisions. These
      factors can disempower women at the point of decision-making. A practice shift is
      needed where women are enabled to have control over decisions. Further, there is
      a need to adhere more rigorously to noncoercive practice when obtaining consent.

PMID- 29171899
TI  - Well-being of nursing staff on specialized units for older patients with combined
      care needs.
AB  - WHAT IS ALREADY KNOWN ABOUT THE SUBJECT: Working in long-term care is seen as a
      stressful, physically and mentally demanding occupation, and thus, nursing staff
      are at risk for work and stress-related diseases. In older patients, psychiatric
      illnesses often occur in combination with physical illnesses, requiring nursing
      care that is specific to these combined care needs. The impact of caring for
      these patients on the mental well-being of nurses is unknown. WHAT THIS PAPER
      ADDS TO EXISTING KNOWLEDGE: Nursing staff working on specialized units for
      patients with combined care needs experience high levels of self-efficacy in
      combination with strong feelings of self-rated competence. Although levels of
      burnout are relatively low, mental healthcare nursing staff is more at risk for
      burnout when working in specialized settings for patients with combined care
      needs than nursing home staff working in specialized settings for these patients.
      Nursing staff characteristics, such as years of working experience and age, seem
      more important in relation to staff well-being than patient characteristics in
      specialized settings for combined care needs. WHAT ARE THE IMPLICATIONS FOR
      PRACTICE: Staff well-being might benefit from specializing care, so that patients
      with similar care needs are placed together and care is focused. The presence of
      specialized care units for older patients with combined care needs can allow for
      both targeted and focused allocation of nursing staff to these units and
      provision of specific training. ABSTRACT: Introduction In older patients,
      psychiatric illnesses frequently exist in tandem with physical illnesses,
      requiring nursing care that is specific to these combined care needs. The impact
      of caring for these patients on the mental well-being of nursing staff is
      unknown. AIM: To investigate whether care characteristics of patients with
      combined care needs are related to the mental well-being of nursing staff.
      METHOD: Well-being of nursing staff was studied within a larger exploratory
      observational cross-sectional study that examined the differences and
      similarities of specialized combined care units in Dutch mental healthcare and
      nursing home settings. RESULTS: Nursing staff across settings, with more than 5
      years of work experience, felt competent in caring for patients with combined
      care needs. No significant effects of care characteristics of patients with
      combined care needs on the work-related well-being of nursing staff were shown.
      Both mental health nursing staff and older employees, however, were found to be
      more at risk for burnout. IMPLICATIONS/CONCLUSION: Staff well-being might benefit
      from placing patients with combined care needs together, so care is focused. The
      presence of specialized care units can allow for both targeted and focused
      allocation of nursing staff to these units and provision of specific training.

PMID- 29171900
TI  - Beating Bias in the Directed Evolution of Proteins: Combining High-Fidelity on
      Chip Solid-Phase Gene Synthesis with Efficient Gene Assembly for Combinatorial
      Library Construction.
AB  - Saturation mutagenesis (SM) constitutes a widely used technique in the directed
      evolution of selective enzymes as catalysts in organic chemistry and in the
      manipulation of metabolic paths and genomes, but the quality of the libraries is
      far from optimal due to the inherent amino acid bias. Herein, it is shown how
      this fundamental problem can be solved by applying high-fidelity solid-phase
      chemical gene synthesis on silicon chips followed by efficient gene assembly.
      Limonene epoxide hydrolase was chosen as the catalyst in the model
      desymmetrization of cyclohexene oxide with the stereoselective formation of (R,R)
      and (S,S)-cyclohexane-1,2-diol. A traditional combinatorial PCR-based SM
      library, produced by simultaneous randomization at several residues by using a
      reduced amino acid alphabet, and the respective synthetic library were
      constructed and compared. Statistical analysis at the DNA level with massive
      sequencing demonstrates that, in the synthetic approach, 97 % of the
      theoretically possible DNA mutants are formed, whereas the traditional SM library
      contained only about 50 %. Screening at the protein level also showed the
      superiority of the synthetic library; many highly (R,R)- and (S,S)-selective
      variants being discovered are not found in the traditional SM library. With the
      prices of synthetic genes decreasing, this approach may point the way to future
      directed evolution.

PMID- 29171901
TI  - Current advances in aptamer-assisted technologies for detecting bacterial and
      fungal toxins.
AB  - Infectious diseases are among the common leading causes of morbidity and
      mortality worldwide. Associated with the emergence of new infectious diseases,
      the increasing number of antimicrobial-resistant isolates presents a serious
      threat to public health and hospitalized patients. A microbial pathogen may
      elicit several host responses and use a variety of mechanisms to evade host
      defences. These methods and mechanisms include capsule, lipopolysaccharides or
      cell wall components, adhesions and toxins. Toxins inhibit phagocytosis, cause
      septic shock and host cell damages by binding to host surface receptors and
      invasion. Bacterial and fungal pathogens are able to apply many different toxin
      dependent mechanisms to disturb signalling pathways and the structural integrity
      of host cells for establishing and maintaining infections Initial techniques for
      analysis of bacterial toxins were based on in vivo or in vitro assessments. There
      is a permanent demand for appropriate detection methods which are affordable,
      practical, careful, rapid, sensitive, efficient and economical. Aptamers are DNA
      or RNA oligonucleotides that are selected by systematic evolution of ligands
      using exponential enrichment (SELEX) methods and can be applied in diagnostic
      applications. This review provides an overview of aptamer-based methods as a
      novel approach for detecting toxins in bacterial and fungal pathogens.

PMID- 29171902
TI  - Early ecological outcomes of natural regeneration and tree plantations for
      restoring agricultural landscapes.
AB  - Mixed tree plantings and natural regeneration are the main restoration approaches
      for recovering tropical forests worldwide. Despite substantial differences in
      implementation costs between these methods, little is known regarding how they
      differ in terms of ecological outcomes, which is key information for guiding
      decision making and cost-effective restoration planning. Here, we compared the
      early ecological outcomes of natural regeneration and tree plantations for
      restoring the Brazilian Atlantic Forest in agricultural landscapes. We assessed
      and compared vegetation structure and composition in young (7-20 yr old) mixed
      tree plantings (PL), second-growth tropical forests established on former
      pastures (SGp), on former Eucalyptus spp. plantations (SGe), and in old-growth
      reference forests (Ref). We sampled trees with diameter at breast height (DBH) 1
      5 cm (saplings) and trees at DBH > 5 cm (trees) in a total of 32 20 * 45 m plots
      established in these landscapes. Overall, the ecological outcomes of natural
      regeneration and restoration plantations were markedly different. SGe forests
      showed higher abundance of large (DBH > 20 cm) nonnative species, of which 98%
      were resprouting Eucalyptus trees, than SGp and PL, and higher total aboveground
      biomass; however, aboveground biomass of native species was higher in PL than in
      SGe. PL forests had lower abundance of native saplings and lianas than both
      naturally established second-growth forests, and lower proportion of animal
      dispersed saplings than SGe, probably due to higher isolation from native forest
      remnants. Rarefied species richness of trees was lower in SGp, intermediate in
      SGe and Ref and higher in PL, whereas rarefied species richness of saplings was
      higher in SG than in Ref. Species composition differed considerably among
      regeneration types. Although these forests are inevitably bound to specific
      landscape contexts and may present varying outcomes as they develop through
      longer time frames, the ecological particularities of forests established through
      different restoration approaches indicate that naturally established forests may
      not show similar outcomes to mixed tree plantings. The results of this study
      underscore the importance that restoration decisions need to be based on more
      robust expectations of outcomes that allow for a better analysis of the cost
      effectiveness of different restoration approaches before scaling-up forest
      restoration in the tropics.

PMID- 29171903
TI  - Public Response to a Near-Miss Nuclear Accident Scenario Varying in Causal
      Attributions and Outcome Uncertainty.
AB  - Many studies have investigated public reactions to nuclear accidents. However,
      few studies focused on more common events when a serious accident could have
      happened but did not. This study evaluated public response (emotional, cognitive,
      and behavioral) over three phases of a near-miss nuclear accident. Simulating a
      loss-of-coolant accident (LOCA) scenario, we manipulated (1) attribution for the
      initial cause of the incident (software failure vs. cyber terrorist attack vs.
      earthquake), (2) attribution for halting the incident (fail-safe system design
      vs. an intervention by an individual expert vs. a chance coincidence), and (3)
      level of uncertainty (certain vs. uncertain) about risk of a future radiation
      leak after the LOCA is halted. A total of 773 respondents were sampled using a 3
      * 3 * 2 between-subjects design. Results from both MANCOVA and structural
      equation modeling (SEM) indicate that respondents experienced more negative
      affect, perceived more risk, and expressed more avoidance behavioral intention
      when the near-miss event was initiated by an external attributed source (e.g.,
      earthquake) compared to an internally attributed source (e.g., software failure).
      Similarly, respondents also indicated greater negative affect, perceived risk,
      and avoidance behavioral intentions when the future impact of the near-miss
      incident on people and the environment remained uncertain. Results from SEM
      analyses also suggested that negative affect predicted risk perception, and both
      predicted avoidance behavior. Affect, risk perception, and avoidance behavior
      demonstrated high stability (i.e., reliability) from one phase to the next.

PMID- 29171904
TI  - Intramolecular Acetyl Transfer to Olefins by Catalytic C-C Bond Activation of
      Unstrained Ketones.
AB  - A rhodium-catalyzed intramolecular acetyl-group transfer has been achieved
      through a "cut and sew" process. The challenge arises from the existence of
      different competitive pathways. Preliminary success has been achieved with
      unstrained enones that contain a biaryl linker. The use of an electron-rich N
      heterocycilc carbene (NHC) ligand is effective to inhibit undesired beta-hydrogen
      elimination. Various 9,10-dihydrophenanthrene derivatives can be prepared with
      excellent functional-group compatibility. The 13 C-labelling study suggests that
      the reaction begins with cleavage of the unstrained C-C bond, followed by
      migratory insertion and reductive elimination.

PMID- 29171905
TI  - Educational nurse-led lifestyle intervention for persons with mental illness.
AB  - Although persons with severe mental illness face an increased risk of mortality
      and of developing negative health outcomes, research has shown that lifestyle
      interventions can sufficiently support their health. In response, this study
      examined a nurse-led lifestyle intervention developed in cooperation with members
      of municipal and county councils to gauge its impact on the quality of life,
      cognitive performance, walking capacity, and body composition of persons with
      severe mental illness. Lasting 26 weeks and involving 38 persons with severe
      mental illness, the intervention prioritised two components: the interpersonal
      relationships of persons with severe mental illness, staff, and group leaders and
      group education about physical and mental health. Pre-post intervention
      measurements of quality of life collected with the Manchester Short Assessment of
      Quality of Life, cognitive performance with the Frontal Systems Behaviour Scale,
      walking capacity with a 6-min walk test, and body composition in terms of waist
      circumference and body mass index were analysed using a nonparametric test
      Wilcoxon signed-rank test. Results suggest that the intervention afforded
      significant improvements in the health-related variables of quality of life,
      cognitive performance, walking capacity, and waist circumference for persons with
      severe mental illness. However, long-term studies with control groups and that
      examine parameters related to cardiovascular risk factors are essential to ensure
      the sustained impact of the intervention.

PMID- 29171907
TI  - Building on NeuroNEXT: Next generation clinics to cure chronic neurological
      disability.

PMID- 29171906
TI  - Risk of a first-ever acute myocardial infarction and all-cause mortality with
      sulphonylurea treatment: A population-based cohort study.
AB  - We investigated the association between the current use of individual
      sulphonylureas and the risk of a first-ever acute myocardial infarction (AMI) and
      all-cause mortality, in a population-based cohort study, using primary care data
      from the Clinical Practice Research Datalink database (2004-2012). New users (N =
      121 869), aged >=18 years, with at least one prescription for a non-insulin
      antidiabetic agent were included. The first prescription defined start of follow
      up. Time-dependent Cox proportional hazard models were used to estimate the risk
      of a first-ever AMI and all-cause mortality associated with the use of individual
      sulphonylureas, and other non-insulin glucose-lowering drugs. No differences in
      risk of a first-ever AMI (adjusted hazard ratio [HR] 1.02, 95% confidence
      interval [CI] 0.70-1.50) or all-cause mortality (adjusted HR 0.97, 95% CI 0.80
      1.17) were observed when comparing gliclazide use with non-gliclazide
      sulphonylurea use. Similar results were found for each individual sulphonylurea.
      As evidence is accumulating that gliclazide is no safer than other
      sulphonylureas, current guidelines suggesting superiority should be carefully
      evaluated.

PMID- 29171908
TI  - An estimation of US horse-owner/caregiver willingness-to-pay for daily use and
      infectious upper respiratory disease treatment options.
AB  - BACKGROUND: Equine injury and disease cause two types of costs for those
      financially responsible for treating and caring for the infected horse(s); direct
      costs of treating the horse and indirect cost of lost use of the horse for a
      period of time to the user of the horse (daily horse use). Indirect costs are
      more difficult to estimate but pose significant financial implications for equine
      owners/caregivers. Additionally, there exists a gap in existing research
      regarding the valuation of infectious treatment options in horses. OBJECTIVE: To
      estimate the value a US horse-owner/caregiver places on daily horse use and
      describe respondents' willingness-to-pay for various attributes of equine
      treatment options. STUDY DESIGN: Online questionnaire survey. METHODS: An online
      questionnaire was provided to equine-owners and caretakers, and owner
      demographic, horse care and horse use information from respondents were
      requested. Additionally, respondents were presented with hypothetical disease
      treatment options with the following attributes: daily dosage, number of days of
      rest required, route of administration and out-of-pocket cost to the
      owner/caretaker through a choice experiment. Data were analysed using a rank
      ordered logit analysis and willingness-to-pay estimates for daily use and
      treatment options were calculated. RESULTS: Results suggest that the average
      horse-owner with an uninsured and insured horse is willing to pay $12.07 (95%
      confidence interval: -$15.01, -$9.69) and $17.95 (95% confidence interval: 
      $25.30, -$11.20) per day to reduce lost use days required (due to need for rest)
      respectively. Respondents showed preferences for oral administration over
      treatments requiring i.m. injections. MAIN LIMITATIONS: As this study employed an
      online survey it was subjected to self-selection bias and a sample size
      calculation was not performed. CONCLUSIONS: Veterinarians and pharmaceutical
      companies may use these results when promoting various treatment options to horse
      owners/caregivers and in product development. Additionally, promotion efforts may
      be targeted towards equine-owners with higher daily use values (owners with
      insured horses).

PMID- 29171909
TI  - LYS12 LysM receptor decelerates Phytophthora palmivora disease progression in
      Lotus japonicus.
AB  - Phytophthora palmivora is a devastating oomycete plant pathogen. We found that P.
      palmivora induces disease in Lotus japonicus and used this interaction to
      identify cellular and molecular events in response to this oomycete, which has a
      broad host range. Transcript quantification revealed that Lys12 was highly and
      rapidly induced during P. palmivora infection. Mutants of Lys12 displayed
      accelerated disease progression, earlier plant death and a lower level of defence
      gene expression than the wild type, while the defence program after chitin,
      laminarin, oligogalacturonide or flg22 treatment and the root symbioses with
      nitrogen-fixing rhizobia and arbuscular mycorrhiza were similar to the wild type.
      On the microbial side, we found that P. palmivora encodes an active chitin
      synthase-like protein, and mycelial growth is impaired after treatment with a
      chitin-synthase inhibitor. However, wheat germ agglutinin-detectable N-acetyl
      glucosamine (GlcNAc) epitopes were not identified when the oomycete was grown in
      vitro or while infecting the roots. This indicates that conventional GlcNAc-mers
      are unlikely to be produced and/or accumulate in P. palmivora cell walls and that
      LYS12 might perceive an unknown carbohydrate. The impact of Lys12 on progression
      of root rot disease, together with the finding that similar genes are present in
      other P. palmivora hosts, suggests that LYS12 might mediate a common early
      response to this pathogen.

PMID- 29171910
TI  - Mutant huntingtin protein expression and blood-spinal cord barrier dysfunction in
      huntington disease.
AB  - OBJECTIVE: The aim of the study was to assess the distribution, frequency, and
      specific location of mutant huntingtin protein (mHTT) aggregates-the pathological
      hallmark of Huntington disease (HD)-within the various compartments of the spinal
      cord and their potential impact on the local vasculature and blood-spinal cord
      barrier (BSCB). METHODS: We performed a series of postmortem immunohistochemical
      and immunofluorescent stainings, as well as Western blot analyses, on cervical
      and lumbar sections of the spinal cord in patients diagnosed with HD (n = 11 of
      all grades of disease severity) along with sex- and age-matched healthy controls
      (n = 9). RESULTS: We observed that mHTT was preferably expressed within the
      anterior horn of the gray matter, in both cervical and lumbar sections. At the
      cellular level, mHTT aggregates were more often encountered in the extracellular
      matrix but could also be observed within cell bodies and neurites as well as
      within the endothelium of blood vessels with an increase in the density of small
      blood vessels in cervical sections of HD cases. These vasculature changes were
      accompanied with features of BSCB leakage, as assessed by the presence of
      increased levels of fibrinogen in the surrounding parenchyma and enhanced
      leukocyte infiltration. INTERPRETATION: This alteration in BSCB integrity may be
      explained, in part, by the dysregulation we found in some of the main proteins
      associated with it such as junctional adhesion molecule-1 and vascular
      endothelial cadherin. These observations have important implications for our
      understanding of HD pathology and may also have significant therapeutic
      implications. Ann Neurol 2017;82:981-994.

PMID- 29171911
TI  - Dermoscopy of different stages of lymphomatoid papulosis.

PMID- 29171912
TI  - Concomitant sensitization to legumin, Fag e 2 and Fag e 5 predicts buckwheat
      allergy.
AB  - BACKGROUND: Buckwheat (Fagopyrum esculentum) has become increasingly popular as a
      healthy food in Europe. However, for sensitized individuals, consumption can
      cause anaphylactic reactions. The aim of this study was to identify individual
      well-characterized buckwheat allergens for component-resolved diagnosis. METHODS:
      Patients were selected by positive skin prick test to buckwheat and divided into
      two groups: (1) sensitized to buckwheat without clinical symptoms and (2)
      buckwheat allergy. Buckwheat proteins were extracted from raw buckwheat seeds,
      purified applying a combination of protein precipitation and chromatographic
      methods, and analyzed by IgE immunoblotting and ELISA. RESULTS: Buckwheat
      allergic patients had a significantly larger median skin prick test weal diameter
      for buckwheat than the sensitized group and the positive control. Also, IgE
      immunoblotting clearly showed a distinct pattern in sera from allergic patients
      when compared to sensitized individuals. Several IgE-reactive proteins were
      purified from crude buckwheat extract, namely legumin (Fag e 1 plus its large
      subunit), Fag e 2 (2S albumin), and newly identified Fag e 5 (vicilin-like) as
      well as hevein-like antimicrobial peptides, designated Fag e 4. All four
      allergens showed superior diagnostic precision compared to extract-based
      ImmunoCAP with high sensitivity as well as high specificity. CONCLUSIONS:
      Patients with clinical symptoms clearly show a distinct allergen recognition
      pattern. We characterized a buckwheat vicilin-like protein as a new relevant
      marker allergen, designated Fag e 5. Additionally, another new allergen, Fag e 4,
      potentially important for cross-reactivity to latex was added to the allergen
      panel of buckwheat. Further, our data show that the full-length legumin
      comprising both, large and small subunit should be applied for component-resolved
      diagnosis. Our data indicate that concomitant sensitization to legumin, Fag e 2
      and Fag e 5, predicts buckwheat allergy.

PMID- 29171913
TI  - MONITOR-GCSF DLBCL subanalysis: Treatment patterns/outcomes with biosimilar
      filgrastim for chemotherapy-induced/febrile neutropenia prophylaxis.
AB  - OBJECTIVE: Prospective data on the use of granulocyte-colony-stimulating factor
      (G-CSF) in non-Hodgkin's lymphoma and its aggressive subtypes, including diffuse
      large B-cell lymphoma (DLBCL), are limited. MONITOR-GCSF is a pan-European,
      multicenter, prospective, observational study aiming to describe treatment
      patterns and clinical outcomes in patients receiving biosimilar filgrastim in the
      prophylaxis of chemotherapy-induced neutropenia (CIN) and febrile neutropenia
      (FN). METHODS: This analysis describes patient characteristics, treatment
      patterns, and outcomes for 245 patients with stage 3 or 4 DLBCL receiving <=6
      chemotherapy cycles as part of MONITOR-GCSF study, including patients aged >=65
      years and >=70 years. Outcomes of interest included the incidence of CIN and FN,
      antibiotic prophylaxis, biosimilar filgrastim prophylaxis, and adverse events
      (AEs). RESULTS: MONITOR-GCSF included 245 patients with DLBCL. Of these patients,
      87 (35.5%) experienced one or more CIN (any grade) episode and 24 (9.8%)
      experienced FN (any grade). The most frequent AE reported was bone pain (n = 7,
      2.9%), followed by arthralgia (n = 2, 0.8%) and back pain (n = 2, 0.8%).
      CONCLUSION: In real-life practice, biosimilar filgrastim demonstrated clinical
      effectiveness and safety in patients with DLBCL. The large percentage of patients
      aged >=65 years adds to the evidence on how to best treat older patients with
      DLBCL receiving myelosuppressive chemotherapy.

PMID- 29171914
TI  - Risk of inferior alveolar nerve injury with coronectomy vs surgical extraction of
      mandibular third molars-A comparison of two techniques and review of the
      literature.
AB  - The removal of mandibular third molar teeth is one of the most common oral
      surgical procedures. In a significant number of patients, it carries a degree of
      associated morbidity, including damage to the inferior alveolar nerve (IAN). For
      this reason, practitioners desire the most up-to-date guidance on the most
      appropriate technique, informed by the best available evidence that will produce
      the lowest incidence of iatrogenic complications. The aim of this study was to
      perform a systematic review comparing the effect of coronectomy vs complete
      surgical extraction of mandibular third molar teeth on the risk of IAN injury and
      other complications in adults. Studies were identified through Embase (1980-2016)
      and Ovid MEDLINE (1946-2016) database searches. Search terms included
      coronectomy, partial root removal, deliberate vital root retention, odontectomy,
      surgical removal, surgical extraction, complete tooth extraction and extract.
      Limits of the study included humans, English language and randomised controlled
      trials (RCTs). Only RCTs comparing IAN damage associated with surgical extraction
      of mandibular third molars vs coronectomy were included. From our database
      searches, we identified two unique RCTs matching the inclusion criteria. Both
      evaluated patients who had specific radiographic signs of intimate relationships
      with the IAN. Upon detailed analysis, the studies were noted to exhibit a high
      risk of bias in many categories, thereby rendering their results inconclusive.
      Although evidence from two RCTs suggests that coronectomy can reduce the risk of
      IAN injury compared to surgical removal of high-risk mandibular third molars, the
      quality of evidence is insufficient to provide definitive conclusions regarding
      the preferred technique.

PMID- 29171916
TI  - Distribution and clinical determinants of time-to-positivity of blood cultures in
      patients with neutropenia.
AB  - OBJECTIVES: Blood cultures (BCs) are essential in the evaluation of neutropenic
      fever. Modern BC systems have significantly reduced the time-to-positivity (TTP)
      of BC. This study explores the probability of bacteraemia when BCs have remained
      negative for different periods of time. METHODS: All adult patients with
      neutropenia and bacteraemia were included (January 2012-February 2016).
      Predictive clinical factors for short (<=16 hours) and long (>24 hours) TTP were
      determined. The residual probability of bacteraemia was estimated for the
      scenario of negative BC 24 hours after collection. RESULTS: The cohort consisted
      of 154 patients, accounting for 190 episodes of bacteraemia. Median age of 61
      years, 60.5% were male. In 123 (64.7%) episodes, BC yielded a single Gram
      positive micro-organism and in 49 (25.8%) a Gram-negative micro-organism (median
      TTP 16.7, 14.5 hours respectively, P < .01). TTP was <=24 hours in 91.6% of
      episodes. Central line-associated bacteraemia was associated with long TTP. The
      probability of bacteraemia if BC had remained negative for 24 hours was 1%-3%.
      CONCLUSIONS: The expected TTP offers guidance in the management of patients with
      neutropenia and suspected bacteraemia. The knowledge of negative BC can support a
      change in working diagnosis, and impact clinical decisions as soon as 24 hours
      after BC collection.

PMID- 29171915
TI  - Targeting hypersensitive corticostriatal terminals in restless legs syndrome.
AB  - OBJECTIVE: The first aim was to demonstrate a previously hypothesized increased
      sensitivity of corticostriatal glutamatergic terminals in the rodent with brain
      iron deficiency (BID), a pathogenetic model of restless legs syndrome (RLS). The
      second aim was to determine whether these putative hypersensitive terminals could
      constitute a significant target for drugs effective in RLS, including dopamine
      agonists (pramipexole and ropinirole) and alpha2 delta ligands (gabapentin).
      METHODS: A recently introduced in vivo optogenetic-microdialysis approach was
      used, which allows the measurement of the extracellular concentration of
      glutamate upon local light-induced stimulation of corticostriatal glutamatergic
      terminals. The method also allows analysis of the effect of local perfusion of
      compounds within the same area being sampled for glutamate. RESULTS: BID rats
      showed hypersensitivity of corticostriatal glutamatergic terminals (lower
      frequency of optogenetic stimulation to induce glutamate release). Both
      hypersensitive and control glutamatergic terminals were significant targets for
      locally perfused pramipexole, ropinirole, and gabapentin, which significantly
      counteracted optogenetically induced glutamate release. The use of selective
      antagonists demonstrated the involvement of dopamine D4 and D2 receptor subtypes
      in the effects of pramipexole. INTERPRETATION: Hypersensitivity of
      corticostriatal glutamatergic terminals can constitute a main pathogenetic
      mechanism of RLS symptoms. Selective D4 receptor agonists, by specifically
      targeting these terminals, should provide a new efficient treatment with fewer
      secondary effects. Ann Neurol 2017;82:951-960.

PMID- 29171918
TI  - Asphyxiated neonates who received active therapeutic hypothermia during transport
      had higher rates of hypocapnia than controls.
AB  - AIM: We investigated the association between active hypothermia and hypocapnia in
      neonates with moderate-to-severe hypoxic-ischaemic encephalopathy (HIE)
      transported after birth. METHODS: This was a retrospective cohort study of
      neonates with HIE born between 2007 and 2011 and transported to Semmelweis
      University, Hungary, for hypothermia treatment before and after we introduced
      active cooling during transport in 2009. Of these, 71 received intensive care
      plus controlled active hypothermia during transport, while the 46 controls just
      received standard intensive care. Incident hypocapnia was defined as a partial
      pressure of carbon-dioxide (pCO2 ) that decreased below 35 mm Hg during
      transport. Multivariable logistic regression investigated the relationship
      between hypothermia and incident hypocapnia. RESULTS: Incident hypocapnia was
      more frequent in the actively cooled transport group (36.6%) than control group
      (17.4%; p = 0.025). pCO2 decreased from a median of 45 to 35 mm Hg (p < 0.0001)
      in the intervention group, but remained unchanged in the controls. After
      adjusting for confounders, hypothermia remained an independent risk factor for
      hypocapnia with an odds ratio (OR) of 4.23 and 95% confidence interval (95% CI)
      of 1.30-13.79. Sedation was associated with a reduction in OR of hypocapnia, at
      0.35 (95% CI 0.12-0.98). CONCLUSIONS: Hypothermia increased the risk of
      hypocapnia in neonates with HIE during transport.

PMID- 29171917
TI  - Increasing motor neuron excitability to treat weakness in sepsis.
AB  - OBJECTIVE: Weakness induced by critical illness (intensive care unit acquired
      weakness) is a major cause of disability in patients and is currently
      untreatable. We recently identified a defect in repetitive firing of lower motor
      neurons as a novel contributor to intensive care unit acquired weakness. To
      develop therapy for intensive care unit acquired weakness, it was necessary to
      determine the mechanism underlying the defect in repetitive firing. METHODS: Both
      computer simulation and in vivo dynamic voltage clamp of spinal motor neurons in
      septic rats were employed to explore potential mechanisms underlying defective
      repetitive firing. RESULTS: Our results suggest alteration in subthreshold
      voltage-activated currents might be the mechanism underlying defective repetitive
      firing. It has been shown previously that pharmacologic activation of serotonin
      receptors on motor neurons increases motor neuron excitability, in part by
      enhancing subthreshold voltage-activated inward currents. Administration of a
      U.S. Food and Drug Administration-approved serotonin agonist (lorcaserin) to
      septic rats greatly improved repetitive firing and motor unit force generation.
      INTERPRETATION: Our findings suggest activation of serotonin receptors with
      lorcaserin may provide the first ever therapy for intensive care unit acquired
      weakness in patients. Ann Neurol 2017;82:961-971.

PMID- 29171919
TI  - Covalent Organic Framework Electrocatalysts for Clean Energy Conversion.
AB  - Covalent organic frameworks (COFs) are promising for catalysis, sensing, gas
      storage, adsorption, optoelectricity, etc. owning to the unprecedented
      combination of large surface area, high crystallinity, tunable pore size, and
      unique molecular architecture. Although COFs are in their initial research stage,
      progress has been made in the design and synthesis of COF-based electrocatalysis
      for the oxygen reduction reaction, oxygen evolution reaction, hydrogen evolution
      reaction, and CO2 reduction in energy conversion and fuel generation. Design
      principles are also established for some of the COF materials toward rational
      design and rapid screening of the best electrocatalysts for a specific
      application. Herein, the recent advances in the design and synthesis of COF-based
      catalysts for clean energy conversion and storage are presented. Future research
      directions and perspectives are also being discussed for the development of
      efficient COF-based electrocatalysts.

PMID- 29171920
TI  - Doing what we can, but knowing our place: Being an ally to promote consumer
      leadership in mental health.
AB  - Consumer participation in all aspects of mental health services is clearly
      articulated as an expectation of contemporary mental health policy. Consumer
      leadership has been demonstrated to be beneficial to mental health services.
      Barriers to implementation have limited the realization of this goal. In this
      discursive paper, we argue that non-consumers who support consumer partnerships
      and leadership (known as 'allies') have an important role to play in facilitating
      and supporting consumers in leadership roles. Allies currently have more
      potential to influence resource allocation, and might be viewed more credibly by
      their peers than consumer leaders themselves. We call for allies to ensure their
      role is one of support and facilitation (doing what they can), rather than
      directing the content or speaking on behalf of the consumer movement (knowing
      their place). In the present study, we address the importance of allies for the
      consumer movement. It proposes some 'rules of engagement' to ensure that allies
      do not intentionally or otherwise encroach on consumer knowledge and expertise,
      so that they maintain the important position of supporting consumers and
      facilitating the valuing and use of consumer knowledge, expertise, and
      ultimately, leadership.

PMID- 29171921
TI  - Developing a Clinically Relevant Tissue Engineered Heart Valve-A Review of
      Current Approaches.
AB  - Tissue engineered heart valves (TEHVs) have the potential to address the
      shortcomings of current implants through the combination of cells and bioactive
      biomaterials that promote growth and proper mechanical function in physiological
      conditions. The ideal TEHV should be anti-thrombogenic, biocompatible, durable,
      and resistant to calcification, and should exhibit a physiological hemodynamic
      profile. In addition, TEHVs may possess the capability to integrate and grow with
      somatic growth, eliminating the need for multiple surgeries children must
      undergo. Thus, this review assesses clinically available heart valve prostheses,
      outlines the design criteria for developing a heart valve, and evaluates three
      types of biomaterials (decellularized, natural, and synthetic) for tissue
      engineering heart valves. While significant progress has been made in
      biomaterials and fabrication techniques, a viable tissue engineered heart valve
      has yet to be translated into a clinical product. Thus, current strategies and
      future perspectives are also discussed to facilitate the development of new
      approaches and considerations for heart valve tissue engineering.

PMID- 29171922
TI  - Less means more: The magnitude of synaptic plasticity along the hippocampal dorso
      ventral axis is inversely related to the expression levels of plasticity-related
      neurotransmitter receptors.
AB  - The dorsoventral axis of the hippocampus exhibits functional differentiations
      with regard to (spatial Vs emotional) learning and information retention (rapid
      encoding Vs long-term storage), as well as its sensitivity to neuromodulation and
      information received from extrahippocampal structures. The mechanisms that
      underlie these differentiations remain unclear. Here, we explored
      neurotransmitter receptor expression along the dorsoventral hippocampal axis and
      compared hippocampal synaptic plasticity in the CA1 region of the dorsal (DH),
      intermediate (IH) and ventral hippocampi (VH). We observed a very distinct
      gradient of expression of the N-methyl-D-aspartate receptor GluN2B subunit in the
      Stratum radiatum (DH< IH< VH). A similar distribution gradient (DH< IH< VH) was
      evident in the hippocampus for GluN1, the metabotropic glutamate receptors mGlu1
      and mGlu2/3, GABAB and the dopamine-D1 receptor. GABAA exhibited the opposite
      expression relationship (DH > IH > VH). Neurotransmitter release probability was
      lowest in DH. Surprisingly, identical afferent stimulation conditions resulted in
      hippocampal synaptic plasticity that was the most robust in the DH, compared with
      IH and VH. These data suggest that differences in hippocampal information
      processing and synaptic plasticity along the dorsoventral axis may relate to
      specific differences in the expression of plasticity-related neurotransmitter
      receptors. This gradient may support the fine-tuning and specificity of
      hippocampal synaptic encoding.

PMID- 29171923
TI  - Clinical and genetic findings in children with central nervous system
      arteriovenous fistulas.
AB  - OBJECTIVE: To assess the spectrum of genetic anomalies in a cohort of children
      presenting at least one cerebral or spinal pial arteriovenous fistula (AVF), and
      to describe their clinical characteristics. METHODS: From 1988 to 2016, all
      consecutive patients with at least one cerebral or spinal pial AVF were screened
      for genetic disease. All patients aged <18 years were included. Symptoms
      associated with AVF were recorded: heart failure, neurological deficit/seizure,
      and hemorrhage. The outcome was assessed using the modified Rankin Scale and
      school performance in children with cerebral AVF and the American Spinal Injury
      Association impairment scale in children with spinal AVF. RESULTS: Forty-three
      children were included. Twenty-five children were male and 18 were female. A
      germline mutation was identified in 23 probands (53.5 +/- 14.9%): 8 in ENG (34.8
      +/- 14.2%), 1 in ACVRL1 (4.3 +/- 6%) leading to a diagnosis of HHT, and 14 in
      RASA1 (60.9 +/- 14.4%) leading to a diagnosis of capillary
      malformation/arteriovenous malformation type 1. No EphB4 gene mutation was
      identified. HHT patients presented a significantly lower rate of heart failure at
      diagnosis (p = 0.047). A trend toward an increased bleeding rate at presentation
      was observed in HHT (p = 0.069) and an increased rate of giant venous pouch in
      children in whom no mutation was identified (p = 0.097). Finally, an association
      with RASA1 mutation was observed in children with associated skin capillary
      hemangioma (p <  0001). INTERPRETATION: These results highlight the importance of
      genetic testing in this setting in view of the high frequency of gene mutations
      in pediatric cerebrospinal AVFs, and show the predominance of RASA1 over HHT
      mutations. Ann Neurol 2017;82:972-980.

PMID- 29171924
TI  - Spin Crossover Nanomaterials: From Fundamental Concepts to Devices.
AB  - Nanoscale spin crossover materials capable of undergoing reversible switching
      between two electronic configurations with markedly different physical properties
      are excellent candidates for various technological applications. In particular,
      they can serve as active materials for storing and processing information in
      photonic, mechanical, electronic, and spintronic devices as well as for
      transducing different forms of energy in sensors and actuators. In this progress
      report, a brief overview on the current state-of-the-art of experimental and
      theoretical studies of nanomaterials displaying spin transition is presented.
      Based on these results, a detailed analysis and discussions in terms of finite
      size effects and other phenomena inherent to the reduced size scale are provided.
      Finally, recent research devices using spin crossover complexes are highlighted,
      emphasizing both challenges and prospects.

PMID- 29171925
TI  - Clinical and photobiological response in eight patients with solar urticaria
      under treatment with omalizumab, and review of the literature.
AB  - BACKGROUND: Solar urticaria (SU) is a rare photodermatosis. Treatment is
      challenging, and outcomes are often disappointing. Omalizumab is an anti-IgE,
      currently approved for treatment of chronic spontaneous urticaria. We sought to
      evaluate therapy with omalizumab in refractory SU and describe predictive factors
      for response. MATERIALS/METHODS: Patients with refractory SU under treatment with
      omalizumab were included in this study. Clinical outcome was evaluated using the
      Urticaria Activity Score 7 (UAS7), Dermatology Life Quality Index (DLQI) and
      Pruritus Visual Analogue Scale (VAS). Complete clinical response (CCR) was
      defined as having an UAS7 = 0, DLQI <6 and VAS = 0. Phototesting was performed
      and compared to baseline. We performed a PubMed search to identify reported cases
      of SU in adults treated with omalizumab, analysing their characteristics in order
      to predict response to omalizumab. RESULTS: Eight patients were included. Median
      age was 45.5 years (range, 23-64). Light spectrum most commonly implicated was UV
      A. Clinical outcomes: 89% (7/8) achieved CCR with omalizumab. Phototesting was
      normal in 42.8% (3/7) of them. In our review, we identified 38 patients
      (including the current case series), and 68.4% showed favourable outcomes with
      omalizumab. Median time since onset of SU was lower in responders. CONCLUSIONS:
      Omalizumab can be an effective treatment in refractory SU.

PMID- 29171926
TI  - Episodic autobiographical memory is associated with variation in the size of
      hippocampal subregions.
AB  - Striking individual differences exist in the human capacity to recollect past
      events, yet, little is known about the neural correlates of such individual
      differences. Studies investigating hippocampal volume in relation to individual
      differences in laboratory measures of episodic memory in young adults suggest
      that whole hippocampal volume is unrelated (or even negatively associated) with
      episodic memory. However, anatomical and functional specialization across
      hippocampal subregions suggests that individual differences in episodic memory
      may be linked to particular hippocampal subregions, as opposed to whole
      hippocampal volume. Given that the DG/CA2/3 circuitry is thought to be especially
      critical for supporting episodic memory in humans, we predicted that the volume
      of this region would be associated with individual variability in episodic
      memory. This prediction was supported using high-resolution MRI of the
      hippocampal subfields and measures of real-world (autobiographical) episodic
      memory. In addition to the association with DG/CA2/3 , we further observed a
      relationship between episodic autobiographical memory and subiculum volume,
      whereas no association was observed with CA1 or with whole hippocampal volume.
      These findings provide insight into the possible neural substrates that mediate
      individual differences in real-world episodic remembering in humans.

PMID- 29171927
TI  - Growth of Black Phosphorus Nanobelts and Microbelts.
AB  - Black phosphorus nanobelts are fabricated with a one-step solid-liquid-solid
      reaction method under ambient pressure, where red phosphorus is used as the
      precursor instead of white phosphorus. The thickness of the as-fabricated
      nanobelts ranges from micrometers to tens of nanometers as studied by scanning
      electron microscopy. Energy dispersive X-ray spectroscopy and X-ray diffraction
      indicate that the nanobelts have the composition and the structure of black
      phosphorus, transmission electron microscopy reveals a typical layered structure
      stacked along the b-axis, and scanning transmission electron microscopy with
      energy dispersive X-ray spectroscopy analysis demonstrates the doping of bismuth
      into the black phosphorus structure. The nanobelt can be directly measured in
      scanning tunneling microscopy in ambient conditions.

PMID- 29171928
TI  - Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue
      Regeneration Applications.
AB  - Poly(lactic-co-glycolic) acid (PLGA) is one of the most versatile biomedical
      polymers, already approved by regulatory authorities to be used in human research
      and clinics. Due to its valuable characteristics, PLGA can be tailored to acquire
      desirable features for control bioactive payload or scaffold matrix. Moreover,
      its chemical modification with other polymers or bioconjugation with molecules
      may render PLGA with functional properties that make it the Holy Grail among the
      synthetic polymers to be applied in the biomedical field. In this review, the
      physical-chemical properties of PLGA, its synthesis, degradation, and conjugation
      with other polymers or molecules are revised in detail, as well as its
      applications in drug delivery and regeneration fields. A particular focus is
      given to successful examples of products already on the market or at the late
      stages of trials, reinforcing the potential of this polymer in the biomedical
      field.

PMID- 29171931
TI  - Actin biophysics in the tradition of Fumio Oosawa: A special issue with
      contributions from participants at the 2016 "Now in Actin" meeting in Nagoya.

PMID- 29171930
TI  - Uric acid lowering in relation to HbA1c reductions with the SGLT2 inhibitor
      tofogliflozin.
AB  - An integrated analysis was performed with data from 4 phase 2 and phase 3 studies
      of tofogliflozin in which patients with type 2 diabetes mellitus received the
      sodium-glucose cotransporter 2 inhibitor tofogliflozin for up to 24 weeks. Sex
      differences, baseline haemoglobin A1c (HbA1c) and serum uric acid (UA) levels,
      and log10 -transformed urinary N-acetyl-beta-D-glucosaminidase ratio were
      significantly correlated with the reduction in serum UA levels at both 4 and 24
      weeks in multivariate analysis (respectively, P < .0001). The decrease in HbA1c
      levels was greatest in the group with the highest baseline HbA1c level (quartile
      4; HbA1c > 8.6%) and lowest in the group with the lowest baseline HbA1c level
      (quartile 1; HbA1c <= 7.4%). The decrease in serum UA levels was greatest in the
      quartile 1 group and lowest in the quartile 4 group. In most groups, the maximum
      decrease in serum UA levels was seen in the first 4 weeks, while the maximum
      decrease in HbA1c was seen at week 24. Thus, serum UA levels were significantly
      decreased in patients with moderate HbA1c levels.

PMID- 29171929
TI  - AHNS Series: Do you know your guidelines? Principles of treatment for locally
      advanced or unresectable head and neck squamous cell carcinoma.
AB  - This article is a continuation of the "Do You Know Your Guidelines" series,
      initiated by the Education committee of the American Head and Neck Society.
      Treatment guidelines for advanced head and neck squamous cell carcinoma are
      reviewed here, including the critical roles of radiotherapy, chemotherapy, and
      the recent application of immunotherapy agents. We will be limiting this
      discussion to include cancers of the oral cavity, oropharynx, hypopharynx, and
      larynx. It should be noted that much of the article pertains to human
      papillomavirus (HPV)-negative oropharyngeal cancer where applicable, as HPV
      positive oropharyngeal squamous cell carcinoma carries a different natural
      history, different prognosis, and now different staging criteria. Additionally,
      the article will not include information on nasopharyngeal or sinus cancers, as
      these latter topics are covered in separate "Do you know your guidelines?"
      installments and these diagnoses carry somewhat different approaches to diagnosis
      and management that diverge from the focus of this article.

PMID- 29171932
TI  - Extremely Small Pyrrhotite Fe7 S8 Nanocrystals with Simultaneous Carbon
      Encapsulation for High-Performance Na-Ion Batteries.
AB  - Na/FeSx batteries have remarkable potential applicability due to their high
      theoretical capacity and cost-effectiveness. However, realization of high power
      capability and long-term cyclability remains a major challenge. Herein, ultrafine
      Fe7 S8 @C nanocrystals (NCs) as a promising anode material for a Na-ion battery
      that addresses the above two issues simultaneously is reported. An Fe7 S8 core
      with quantum size (~10 nm) overcomes the kinetic and thermodynamic constraints of
      the Na-S conversion reaction. In addition, the high degree of interconnection
      through carbon shells improves the electronic transport along the structure. As a
      result, the Fe7 S8 @C NCs electrode achieves excellent power capability of 550 mA
      h g-1 (~79% retention of its theoretical capacity) at a current rate of 2700 mA g
      1 . Furthermore, a conformal carbon shell acts as a buffer layer to prevent
      severe volume change, which provides outstanding cyclability of ~447 mA h g-1
      after 1000 cycles (~71% retention of the initial charge capacity).

PMID- 29171933
TI  - Transpalpebral ultrasonographic measurement of the optic nerve sheath diameter in
      healthy dogs.
AB  - OBJECTIVE: To develop a reference range for ultrasonographically measured optic
      nerve sheath diameter (ONSD-US) in dogs. We hypothesized that ONSD-US can be
      measured reliably and is associated with weight but not age, sex, or body
      condition score (BCS), and that the relationship between weight and ONSD-US in
      dogs is allometric due to canine size variations. DESIGN: Prospective,
      observational study. SETTING: University teaching hospital. ANIMALS: Seventy
      eight healthy adult dogs. INTERVENTIONS: The ONSD was measured by a standardized
      transpalpebral approach. MEASUREMENTS AND MAIN RESULTS: Regression analysis
      showed the relationship between weight and ONSD was better fit with a linear
      model (R2 = 0.8510) than an allometric model (R2 = 0.7917). Multiple regression
      analysis showed ONSD is associated with weight (P < 0.0001), age (P = 0.0021),
      and BCS (P = 0.0007), but not with sex. Dominance analysis showed 94.6% of the
      variance explained by the model was due to weight. Intraclass correlation
      coefficient (ICC) analysis showed excellent interobserver (ICC = 0.9338-0.9608)
      and intraobserver (ICC = 0.9893) reliability. CONCLUSIONS: These results suggest
      that ONSD-US may be reliably measured in dogs using our described transpalpebral
      approach, and we have calculated prediction intervals based on body weight.
      Future studies are needed to determine if ONSD-US measurements are associated
      with intracranial hypertension as shown in human medicine.

PMID- 29171934
TI  - Design, Synthesis, and Evaluation of omega-(Isothiocyanato)alkylphosphinates and
      Phosphine Oxides as Antiproliferative Agents.
AB  - A series of 21 novel, structurally diverse omega
      (isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and
      synthesized in moderate to good yields. The synthesized compounds were evaluated
      for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines.
      The biological activity of the synthesized compounds was higher than that of
      natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The
      antiproliferative activity of selected ITCs was also tested on selected cancer
      cell lines: A549, MESSA and MESSA/DX-5, HL60 and HL60MX2, BALB/3T3, and 4T1.
      These compounds were assessed for their mechanism of action as inducers of cell
      cycle arrest and apoptosis. Ethyl (6-isothiocyanatohexyl)(phenyl)phosphinate (71)
      was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor
      activity, similar to that benzyl isothiocyanate and cyclophosphamide.

PMID- 29171935
TI  - Single molecule real-time DNA sequencing of HLA genes at ultra-high resolution
      from 126 International HLA and Immunogenetics Workshop cell lines.
AB  - The hyperpolymorphic HLA genes play important roles in disease and
      transplantation and act as genetic markers of migration and evolution. A panel of
      107 B-lymphoblastoid cell lines (B-LCLs) was established in 1987 at the 10th
      International Histocompatibility Workshop as a resource for the immunogenetics
      community. These B-LCLs are well characterised and represent diverse ethnicities
      and HLA haplotypes. Here we have applied Pacific Biosciences' Single Molecule
      Real-Time (SMRT) DNA sequencing to HLA type 126 B-LCL, including the 107
      International HLA and Immunogenetics Workshop (IHIW) cells, to ultra-high
      resolution. Amplicon sequencing of full-length HLA class I genes (HLA-A, -B and 
      C) and partial length HLA class II genes (HLA-DRB1, -DQB1 and -DPB1) was
      performed. We typed a total of 931 HLA alleles, 895 (96%) of which were
      consistent with the typing in the IPD-IMGT/HLA Database (Release 3.27.0, January
      20, 2017), with 595 (64%) typed at a higher resolution. Discrepant types,
      including novel alleles (n = 10) and changes in zygosity (n = 13), as well as
      previously unreported types (n = 34) were observed. In addition, patterns of
      linkage disequilibrium were distinguished by four-field resolution typing of HLA
      B and HLA-C. By improving and standardising the HLA typing of these B-LCLs, we
      have ensured their continued usefulness as a resource for the immunogenetics
      community in the age of next generation DNA sequencing.

PMID- 29171936
TI  - BRAF internal deletions and resistance to BRAF/MEK inhibitor therapy.
AB  - BRAF and MEK inhibitors have improved clinical outcomes in advanced, BRAFV600 
      mutated melanomas. Acquired resistance occurs in most patients, with numerous and
      diverse drivers. We obtained pretreatment and progression biopsies from a patient
      who progressed on dabrafenib and trametinib. In addition to a preserved BRAFV600E
      mutation, an internal deletion (rearrangement) of BRAF was observed in the
      progression sample. This deletion involved exons 2-8, which includes the Ras
      binding domain, and is analogous to previously documented BRAF fusions and splice
      variants known to reactivate RAS-RAF-MEK-ERK signaling. In a large cohort of
      melanomas, 10 additional internal deletions were identified (0.4% of all
      melanomas; nine of which had concurrent BRAF mutations), as well as sporadically
      in other tumor types. Thus, we describe a novel mechanism of resistance to BRAF
      and MEK inhibition.

PMID- 29171937
TI  - Incidence rate and patient characteristics of severe hypoglycemia in treated type
      2 diabetes mellitus patients in Japan: Retrospective Diagnosis Procedure
      Combination database analysis.
AB  - AIMS/INTRODUCTION: To evaluate the incidence rate of and identify factors
      associated with severe hypoglycemic episodes in patients with treated type 2
      diabetes mellitus. MATERIALS AND METHODS: Using Diagnosis Procedure Combination
      hospital-based medical database, we carried out a retrospective cohort study to
      assess the incidence rate of severe hypoglycemia in treated type 2 diabetes
      mellitus patients. We evaluated the associations between severe hypoglycemia and
      age, sex, complications, and current use of insulin or sulfonylurea (SU) in a
      nested case-control study. RESULTS: Of 166,806 eligible patients, 1,242 had
      episodes of severe hypoglycemia during the observational period. The incidence
      rate of the first hypoglycemic events was 3.70/1,000 patient years. Based on the
      nested case-control analysis, age was associated with hypoglycemic events with
      adjusted odds ratios (ORs) of 1.64 or 65-74-year-old patients and 3.79 for >=75
      year-old patients in comparison with 20-64-year-old patients. Comorbidities, such
      as cognitive impairment, cancer, macrovascular disease and diabetic complications
      (retinopathy, nephropathy and neuropathy), were associated with severe
      hypoglycemia, with adjusted ORs ranging from 1.25 to 3.80. Severe hypoglycemic
      events also increased in patients with current use of both SU and insulin, either
      SU or insulin, with adjusted ORs of 18.36, 6.31 or 14.07, respectively, compared
      with patients with other antihyperglycemic agents. In patients with an SU
      glimepiride, adjusted ORs increased dose-dependently from 3.65 (<=1 mg) to 13.34
      (>2 mg). CONCLUSIONS: The incidence rate of severe hypoglycemia in this cohort
      was 3.70/1,000 patient years. Age, cognitive impairment, cancer, diabetic
      complications, current use of insulin + SU and SU dosage were identified as risk
      factors for severe hypoglycemia.

PMID- 29171938
TI  - Complementary Strategies Toward the Aqueous Processing of High-Voltage LiNi0.5
      Mn1.5 O4 Lithium-Ion Cathodes.
AB  - Increasing the environmental benignity of lithium-ion batteries is one of the
      greatest challenges for their large-scale deployment. Toward this end, we present
      herein a strategy to enable the aqueous processing of high-voltage LiNi0.5 Mn1.5
      O4 (LNMO) cathodes, which are considered highly, if not the most, promising for
      the realization of cobalt-free next-generation lithium-ion cathodes. Combining
      the addition of phosphoric acid with the cross-linking of sodium carboxymethyl
      cellulose by means of citric acid, aqueously processed electrodes with excellent
      performance are produced. The combined approach offers synergistic benefits,
      resulting in stable cycling performance and excellent coulombic efficiency (98.96
      %) in lithium-metal cells. Remarkably, this approach can be easily incorporated
      into standard electrode preparation processes with no additional processing step.

PMID- 29171939
TI  - Initial flow cytometric evaluation of the Clearllab lymphoid screen.
AB  - INTRODUCTION: Flow cytometric immunophenotyping (FCI) is an integral part in the
      diagnosis and classification of hematologic malignancies. FCI results also
      influence therapeutic decisions and disease prognosis. ClearLLab LS is a 12
      antibody 10-color cocktail provided in dry format designed as a screen for
      patients suspected of having hematolymphoid disease. METHODS: A blinded
      comparison between ClearLLab LS, (CD8-FITC, Kappa-FITC,CD4-PE, Lambda-PE, CD19
      ECD, CD56-PE-Cy5.5, CD10-PE-Cy7, CD34-APC, CD5-APC-A700, CD20-APC-A750, CD3-PB,
      and CD45-KrO), ClearLLab Reagents (five-color, 17-antibodies) and individual
      Laboratory Developed Tests (LDTs), was conducted at four laboratories. Evaluation
      of ClearLLab LS was performed on 210 specimens, compared to the five-color
      ClearLLab Reagents (IVD and CE-IVD), and a subset (n = 167) to LDTs. RESULTS:
      ClearLLab LS showed good agreement to ClearLLab Reagents in detecting the absence
      (104/104) or presence (106/106) of abnormal populations. Of specimens with
      abnormal populations the ClearLLab LS agreed with the ClearLLab Reagent for
      neoplasm maturity assessment (70/70 mature and 36/36 immature). Out of 167
      specimens with LDTs results, 86 contained abnormal population(s), ClearLLab LS
      detected 82 (95.3%) of cases. Of the 4 cases not detected by ClearLLab LS, 3 were
      plasma cell neoplasms and 1 was a mature T cell malignancy. Eighty-one samples
      with no hematological malignancy as analyzed by LDT were also negative by
      ClearLLab LS (100% agreement). ClearLLab LS agreed with LDTs assessment of
      neoplasms' maturity (55/55 mature and 27/27 immature). CONCLUSION: ClearLLab LS
      screening tube showed excellent agreement between ClearLLab Reagents and with
      LDT's. The presence of CD34 and CD10 in the tube allowed the detection of blast
      populations in several acute leukemias and myeloid neoplasms that were tested.
      (c) 2017 International Clinical Cytometry Society.

PMID- 29171942
TI  - Erratum.

PMID- 29171940
TI  - HLAs: Key regulators of T-cell-mediated drug hypersensitivity.
AB  - Adverse drug reactions (ADR) can be broadly categorised as either on-target or
      off-target. On-target ADRs arise as a direct consequence of the pharmacological
      properties of the drug and are therefore predictable and dose-dependent. On
      target ADRs comprise the majority (>80%) of ADRs, relate to the drug's
      interaction with its known pharmacological target and are a result of a complex
      interplay of genetic and ecologic factors. In contrast, off-target ADRs,
      including immune-mediated ADRs (IM-ADRs), are due to unintended pharmacological
      interactions such as inadvertent ligation of host cell receptors or non
      pharmacological interactions mediated through an adaptive immune response. IM
      ADRs can be classified according to the primary immune cell involved and include
      B-cell-mediated (Gell-Coombs type I-III reactions) and T-cell-mediated (Gell
      Coombs type IV or delayed hypersensitivity) reactions. IM-ADRs mediated by T
      cells are associated with phenotypically distinct clinical diagnoses and can vary
      from a mild delayed rash to a life-threatening cutaneous, systemic or organ
      disease, such as Stephen Johnson syndrome/toxic epidermal necrolysis, drug
      reaction with eosinophilia and systemic symptoms and drug-induced liver disease.
      T-cell-mediated ADRs are strongly linked to the carriage of particular HLA risk
      alleles which are in the case of abacavir hypersensitivity and HLA-B*57:01 has
      led to translation into the clinic as a routine screening test. In this review,
      we will discuss the immunogenetics and pathogenesis of IM-ADRs and how HLA
      associations inform both pre-drug screening strategies and mechanistic
      understanding.

PMID- 29171943
TI  - [Image of the month. Acute bowel obstruction due to torsion of a large uterine
      fibroid].

PMID- 29171941
TI  - Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A
      multinational, prospective, controlled, randomized trial.
AB  - Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no
      proven effective treatment for sAH, which is why early transplantation has been
      increasingly discussed. Hepatoblastoma-derived C3A cells express anti
      inflammatory proteins and growth factors and were tested in an extracorporeal
      cellular therapy (ELAD) study to establish their effect on survival for subjects
      with sAH. Adults with sAH, bilirubin >=8 mg/dL, Maddrey's discriminant function
      >= 32, and Model for End-Stage Liver Disease (MELD) score <= 35 were randomized
      to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment
      plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was
      assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were
      enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline
      characteristics showed no significant differences between groups and within
      subgroups. There was no significant difference in serious adverse events between
      the 2 groups. In an analysis of the intent-to-treat population, there was no
      difference in OS (51.0% versus 49.5%). The study failed its primary and secondary
      end point in a population with sAH and with a MELD ranging from 18 to 35 and no
      upper age limit. In the prespecified analysis of subjects with MELD < 28 (n =
      120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus
      53.6%; P = .08). Regression analysis identified high creatinine and international
      normalized ratio, but not bilirubin, as the MELD components predicting negative
      outcomes with ELAD. A new trial investigating a potential benefit of ELAD in
      younger subjects with sufficient renal function and less severe coagulopathy has
      been initiated. Liver Transplantation 24 380-393 2018 AASLD.

PMID- 29171944
TI  - [Central serous chorioretinopathy following the use of phosphodiesterase 5
      inhibitors].
AB  - Central serous chorioretinopathy occurs primarily in young caucasian men. It is
      characterized by the development of a serous detachment of the sensory retina
      with the apparition of a relative central scotomata. An association with
      phosphodiesterase 5 inhibitors is reported in some articles. We described two
      cases of central serous chorioretinopathy following the use of tadalafil and
      sildenafil.

PMID- 29171945
TI  - [Hematocolpos : an unappreciated diagnosis of hymen imperforation].
AB  - The imperforation of the hymen is a relatively rare congenital malformation. It
      usually manifests itself in adolescence by a hematocolpos. Hematocolpos is the
      vaginal retention of menstrual blood at puberty. It results clinically in painful
      amenorrhea and more rarely in a pelvic mass syndrome. The diagnosis is easy, it
      is primarily clinical. Pelvic ultrasound and nuclear magnetic resonance are the
      complementary examinations to be performed as a preoperative assessment and to
      detect any associated genito-urinary malformations.

PMID- 29171946
TI  - [Cardiac rehabilitation, state of the art 2017].
AB  - Cardiovascular disease remains the leading cause of death in western countries.
      Despite advances in acute management of patients, secondary prevention remains
      essential and should include cardiac rehabilitation. Recent data have confirmed
      the interest of this management in the various conventional indications :
      coronary disease, valvular heart disease, heart failure and heart
      transplantation. New indications emerge with some benefit that should be
      evaluated : ventricular assistance, pulmonary hypertension, trans-catheter aortic
      valve implantation. However, the different rehabilitation programs proposed are
      still too uneven in content and duration and the number of patients participating
      in these programs remains low. Home based cardiac rehabilitation technologies
      have already shown some effectiveness and could improve some of the weaknesses of
      rehabilitation programs. Again protocols and tools need to be improved and
      standardized. The budgetary impact will also have to be studied further.

PMID- 29171947
TI  - [Perception by the oncologist of the parental distress in childhood cancer
      survivor].
AB  - The aim of the study was to assess the degree of similarity between the distress
      expressed by parents of a child cancer survivor and the distress perceived by the
      oncologist. Overall, 61 parents of a child cancer survivor (between 4 and 6 years
      of cancer remission) were recruited in Belgian hospitals (Province of Liege).
      Parents filled out questionnaires about the intolerance of uncertainty (IUS),
      positive beliefs about worry (WW-II), parental worries about the evolution of
      their child's health (QIPS-R15), problem orientation (NPOQ), cognitive avoidance
      (CAQ), ruminations (Mini-CERTS), and anxiety/depression (HADS). Eight oncologists
      who having taken care of the child filled out the "OncoMed" questionnaire that
      examines their perception of the parental distress (e.g. anxiety, worries).
      Parents suffered from anxiety,worries about their child's health and showed a low
      level of tolerance of uncertainty. Overall, oncologists demonstrated a low
      perceived distress compared to the level of parental distress. The study
      highlights the need to detect early parents who are intolerant of uncertainty in
      order to offer them an efficient psychological follow-up. This study underlines
      finally the necessity to develop medical perception tools about the distress in
      order to strengthen the medical communication and the follow-up of these
      families.

PMID- 29171948
TI  - [Platypnea-orthodeoxia syndrome : an insightful clinical observation].
AB  - We report the case of a patient admitted to the Intensive Care Unit with dyspnea
      and refractory hypoxemia after surgical resection of a benign bronchogenic cyst.
      Etiological research approach excluded conventional postoperative hypoxemia
      causes. Thereafter a platypnea-orthodeoxia syndrome has been diagnosed.
      Additional tests will demonstrate the existence of a patent foramen ovale. This
      diagnosis was suitable with the patient's syndrome and was eligible for
      percutaneous closure procedure allowing immediate resolution of symptoms and
      confirming the diagnosis.

PMID- 29171949
TI  - [Multidisciplinary team meetings : experiences and difficulties of ambulatory
      care professionals. A qualitative study.]
AB  - Multidisciplinary work is gaining importance with the ageing of the population,
      an increase in the number of chronically ill patients, and patients' preference
      for homebased healthcare. Multidisciplinary team meetings (MDTMs) were designed
      to foster dialogue between care providers of patients with decreasing autonomy.
      Despite being financed by the Health Insurance, few professionals use it. This
      study aimed at an exploration of the professionals' reasons for this lack of
      MDTM. Semi-structured interviews with health and social care providers who had
      participated in an MDTM were analysed thematically by two researchers working
      independently. All of the professionals recognised the importance of MDTMs in
      improving support for patients and their relatives. Each person's presence at the
      MDTM helped participants to define their scope of action, to become acquainted
      with one another, and to coordinate their work. Administrative and logistical
      limitations were cited as obstacles, as was the absence of a multidisciplinary
      working culture. MDTMs place the patient at the forefront, and allow
      professionals to meet and agree on a treatment plan. A range of different working
      practices and cultures challenges the method.

PMID- 29171950
TI  - [Evolocumab (Repatha(r)) : a human monoclonal antibody against PCSK9 protein as
      potent cholesterol-lowering therapy].
AB  - Evolocumab is a fully human monoclonal antibody (mAb) targeting ProProtein
      Convertase Subtilisin/Kexin 9 (PCSK9). PCSK9 is a circulating enzyme secreted by
      the liver and plays a key role in the LDL-Receptors (LDL-R) turnover. Binding of
      PCSK9 on the extracellular part of LDL-R is responsible for its degradation in
      the lysosome instead of its recycling to the cell surface, thereby producing a
      reduction in the number of LDL-R on the cell surface, a decreased LDL-C uptake
      and increased levels of LDL-C. Inhibiting PCSK9 is a new way to markedly reduce
      LDL-C. The development of mAbs that bind the extracellular PCSK9 and prevent its
      interaction with LDL-R is the most advanced and tested approach to PCSK9
      inhibition to date. The clinical efficacy and safety of evolocumab have been
      studied in a number of controlled trials versus placebo or versus active
      comparator (ezetimibe) during 12 to 76 weeks. Added on statin, evolocumab reduced
      LDL-C up to 50 to 60 % from baseline. Evolocumab also reduced LCL-C in
      monotherapy in statin-intolerant patients. Evolocumab also significally reduced
      total cholesterol, non-HDL cholesterol, apoprotein B and lipoprotein(a). Safety
      and tolerance were good. Evolocumab is commercialized under the trade name
      Repatha(r) and administrated subcutaneously at the dose of 140 mg every 2 weeks
      or 420 mg once per month. Repatha(r) is approved in Belgium, with conditions, for
      the treatment of hypercholesterolemia in patients with heterozygous (HFe) and
      homozygous (HFo) familial hypercholesterolemia.

PMID- 29171951
TI  - [Diagnosis of lower limb pain in a diabetic patient].
AB  - By presenting this clinical case, we aim at discussing the diagnosis between
      arteriopathy, neuropathy and osteoarticular pathology in a patient with type 2
      diabetes who complains of lower limb pain. We emphasize the role of a global
      medical approach based upon anamnesis and clinical exam, which should contribute
      to select the most helpful paraclinical investigations.

PMID- 29171952
TI  - Dynamics of Radical Ions of Hydroxyhexafluoroisopropyl-Substituted Benzenes.
AB  - Fluorination of resist materials is an effective method used to enhance the
      energy deposition of extreme ultraviolet (EUV) light in the fabrication of next
      generation semiconductor devices. The dynamics of radical ions are important to
      understand when considering the radiation-chemistry of the resist materials using
      EUV and electron beam lithography. Here, the dynamics of the radical anions and
      cations of benzenes with one or two 2-hydroxyhexafluoroisopropyl groups (HFABs)
      were studied using radiolysis techniques. The formation of dimer radical cations
      was observed only in the monosubstituted benzene solutions of 1,2-dichloroethane.
      If the compound contained more than two substituents, it was found to hinder the
      necessary pi-pi overlapping. Pulse radiolysis of HFABs in tetrahydrofuran showed
      a characteristic spectral shift of the radical anion within the region of several
      hundred nanoseconds. From the results of low-temperature spectroscopy and density
      functional calculations, it is suggested that excess electrons of the 2
      hydroxyhexafluoroisopropyl group of the radical anions cause dissociation into
      neutral radicals.

PMID- 29171953
TI  - Topologically Micropatterned Collagen and Poly(epsilon-caprolactone) Struts
      Fabricated Using the Poly(vinyl alcohol) Fibrillation/Leaching Process To Develop
      Efficiently Engineered Skeletal Muscle Tissue.
AB  - Optimally designed three-dimensional (3D) biomedical scaffolds for skeletal
      muscle tissue regeneration pose significant research challenges. Currently, most
      studies on scaffolds focus on the two-dimensional (2D) surface structures that
      are patterned in the micro-/nanoscales with various repeating sizes and shapes to
      induce the alignment of myoblasts and myotube formation. The 2D patterned surface
      clearly provides effective analytical results of pattern size and shape of the
      myoblast alignment and differentiation. However, it is inconvenient in terms of
      the direct application for clinical usage due to the limited thickness and 3D
      shapeability. Hence, the present study suggests an innovative hydrogel or
      synthetic structure that consists of uniaxially surface-patterned cylindrical
      struts for skeleton muscle regeneration. The alignment of the pattern on the
      hydrogel (collagen) and poly(epsilon-caprolactone) struts was attained with the
      fibrillation of poly(vinyl alcohol) and the leaching process. Various cell
      culture results indicate that the C2C12 cells on the micropatterned collagen
      structure were fully aligned, and that a significantly high level of myotube
      formation was achieved when compared to the collagen structures that were not
      treated with the micropatterning process.

PMID- 29171954
TI  - Mitochondrial-Targeting Lonidamine-Doxorubicin Nanoparticles for Synergistic
      Chemotherapy to Conquer Drug Resistance.
AB  - Lonidamine (LND) can act on mitochondria and inhibit energy metabolism in cancer
      cells and therefore has been used together with chemotherapy drugs for
      synergistically enhanced therapeutic efficacy. However, its use is hindered by
      the poor solubility and slow diffusion in the cytoplasm. To address these
      problems, we designed and prepared aqueous dispersible nanoparticles (NPs)
      containing integrated components including triphenylphosphine (TPP) to target the
      mitochondria of cells and LND and doxorubicin (DOX) for synergistic cancer
      treatment and conquering drug resistance. This design allows the NPs to
      concentrate in the mitochondria of cells, solve the low solubility of LND, and
      contain very high load of LND and DOX in comparison with previously reported drug
      delivery systems based on various carrier nanomaterials. Detailed mechanism
      studies reveal that TPP-LND-DOX NPs could induce significant reactive oxygen
      species production, mitochondrial membrane potential decrease, and mitochondrial
      apoptosis pathway, thereby leading to great cytotoxicity in cancer cells. In vivo
      anticancer activities indicate that TPP-LND-DOX NPs exhibit the highest efficacy
      in tumor inhibition among all tested groups and show high effectiveness in drug
      resistant model. This work demonstrates the potential use of our TPP-LND-DOX NPs
      to jointly promote the mitochondria apoptosis pathway and contribute to conquer
      drug resistance in cancer therapy.

PMID- 29171955
TI  - Energetics of van der Waals Adsorption on the Metal-Organic Framework NU-1000
      with Zr6-oxo, Hydroxo, and Aqua Nodes.
AB  - We report measurements of adsorption isotherms and the determination of the
      isosteric heats of adsorption of several small gases (H2, D2, Ne, N2, CO, CH4,
      C2H6, Ar, Kr, and Xe) on the metal-organic framework (MOF) NU-1000, which is one
      of the most thermally stable MOFs. It has transition-metal nodes of formula
      Zr6(MU3-OH)4(MU3-O)4(OH)4(OH2)4 that resemble hydrated ZrO2 clusters and can
      serve as catalysts or catalyst supports. The linkers in this MOF are pyrenes
      linked to the nodes via the carboxylate groups of benzoates. The broad range of
      adsorbates studied here allows us to compare trends both with adsorption on other
      surfaces and with density functional calculations also presented here. The
      experimental isotherms indicate similar filling of the MOF surface by the
      different gases, starting with strong adsorption sites near the Zr atoms, a
      result corroborated by the density functional calculations. This adsorption is
      followed by the filling of other adsorption sites on the nodes and organic
      framework. Capillary condensation occurs in wide pores after completion of a
      monolayer. The total amount adsorbed for all the gases is the equivalent of two
      complete monolayers. The experimental isosteric heats of adsorption are nearly
      proportional to the atom-atom (or molecule-molecule) Lennard-Jones well-depth
      parameters of the adsorbates but ~13-fold larger. The density functional
      calculations show a similar trend but with much more scatter and heats that are
      usually greater (by 30%, on average).

PMID- 29171956
TI  - The Montreal Cognitive Assessment (MoCA) in a population-based sample of Turkish
      migrants living in Germany.
AB  - OBJECTIVES: Data on cognitive testing in migrants in Germany are scarce. We aimed
      to evaluate the Montreal Cognitive Assessment (MoCA) in Turkish migrants in
      Berlin and its association with demographics and health-related variables.
      METHOD: For this cross-sectional study, a random sample of persons with Turkish
      names was drawn from the registration-office. Cognitive function was assessed
      using the MoCA; 0 = worst, 30 = best total score. Multivariable linear regression
      models were calculated to determine associated factors with the total MoCA-score.
      RESULTS: In our analyses we included 282 participants (50% female), mean age 42.3
      +/- 11.9 years (mean +/- standard deviation (SD)). The mean +/- SD MoCA score was
      23.3 +/- 4.3. In the multivariable analysis, higher education (beta = 2.68; p <
      0.001), and chosing the German version of the MoCA (beta = -1.13; p = 0.026),
      were associated with higher MoCA-scores, whereas higher age (beta = -0.08; p =
      0.002) was associated with lower MoCA scores. CONCLUSION: In our study, a higher
      educational level, lower age, and German as the preferred test language (as
      compared to Turkish) were positively associated with the cognitive performance of
      Berliners with Turkish roots. To examine neurocognitive health of migrants,
      longitudinal population-based and clinical cohort studies that specifically
      compare migrants and their descendants with the original population of their home
      countries are required.

PMID- 29171957
TI  - Carotid artery longitudinal wall motion: regulatory factors and implications for
      arterial health.
AB  - The carotid artery wall moves longitudinally along the length of the vessel,
      although little is known about what causes this motion, or what health
      information it represents. The overarching purpose of this dissertation was to
      investigate the regulation of carotid artery longitudinal wall motion (CALM) in
      humans, as well as how CALM can be used to infer information about arterial
      health. Through observational and experimental designs, we tested evidence for a
      structural ventricular-vascular coupling effect, which postulates that systolic
      anterograde CALM is influenced by the forward blood shear rate while systolic
      retrograde CALM is influenced by left ventricular rotation, although the data
      suggest a moderate influence of left ventricular rotation, and minimal influence
      of shear rate. In cross-sectional analyses, we demonstrated that diastolic CALM
      variables are better related to age and health status compared with systolic CALM
      displacement and that this relationship was independent of traditional measures
      of arterial stiffness. These experimental and observational results directed the
      use of diastolic CALM as a potential indicator of arterial health in subsequent
      studies, owing to the relative independence from systolic events. While there was
      no effect of 12 weeks of exercise training in healthy men on diastolic CALM
      variables, we observed increased systolic retrograde CALM and diastolic CALM
      acceleration in men with a history of resistance exercise training compared with
      sedentary men, suggesting an effect of habitual exercise training. Our novel
      findings suggest that CALM is regulated by a complex system, in part related to
      both arterial wall structure and ventricular-vascular coupling, and may have
      clinical value in complimenting measures of traditional arterial stiffness in
      humans. Future studies should examine whether local changes to arterial wall
      structure or indirect changes in regulatory control dictate differences in CALM
      with aging and with chronic exercise training, before integrating CALM into
      routine measurement of arterial health.

PMID- 29171958
TI  - Fecal incontinence as a moderator between dietary intake and depressive symptoms
      among a sample of older adults obtained from the National Health and Nutrition
      Examination Survey (NHANES).
AB  - OBJECTIVES: Many studies have established a relationship between diet and mental
      health, as well as the importance of bowel health. Further, with increased
      evidence of a gut-brain bidirectional relationship, an indication of dysbiosis as
      a potential moderator between diet and depression may be a viable target for
      future interventions. The current study investigated the relationship between
      diet and depressive symptoms (DS) among older adults, as well as gender, and
      whether a symptom of dysbiosis, fecal incontinence severity (FIS), moderated this
      relationship. METHOD: Using moderated regressions, we examined whether FIS
      moderates the relationship between diet and DS while controlling for covariates
      in the overall sample (N = 1918), as well as among the male (n = 841) and female
      sample (n = 1077). The dietary variables were reduced using a factor analysis.
      RESULTS: Results indicated significant moderating effects of FIS between
      Component 4 and polyunsaturated fatty acids (PFA) in the overall sample.
      Component 4, protein, carbohydrates, and alcohol were significant in males only
      while PFA only in females. Further analysis of protein/carbohydrate ratio groups
      indicated significant differences within males. Higher scores of FIS were related
      to higher DS and less consumption of Component 4 nutrients, PFA, and protein.
      Males that consumed higher protein and carbohydrates resulted in lower DS with
      increased FIS. CONCLUSION: Outcomes from the current study provide further
      evidence of the importance of healthy bowel function and the potential of
      modifying the diet to improve DS in older adults.

PMID- 29171959
TI  - The influence of social support and perceived stress on response time
      inconsistency.
AB  - OBJECTIVES: Lack of social support and high levels of stress represent
      potentially modifiable risk factors for cognitive aging. In this study we
      examined the relationships between these two risk factors and response time
      inconsistency (RTI), or trial-to-trial variability in choice response time tasks.
      RTI is an early indicator of declining cognitive health, and examining the
      influence of modifiable psychosocial risk factors on RTI is important for
      understanding and promoting cognitive health during adulthood and old age.
      METHODS: Using data from a community sample study (n = 317; Mage = 49, range = 19
      83), we examined the effects of social support, including size of network and
      satisfaction with support, global perceived stress, and their interactions on
      RTI. RESULTS: Neither size of network nor satisfaction with support was
      associated with RTI independent of perceived stress. Stress was positively
      associated with increased RTI on all tasks, independent of social support.
      Perceived stress did not interact with either dimension of social support to
      predict RTI, and perceived stress effects were invariant across age and sex.
      CONCLUSION: Perceived stress, but not social support, may be a unique and
      modifiable risk factor for normal and pathological cognitive aging. Discussion
      focuses on the importance of perceived stress and its impact on RTI in supporting
      cognitive health in adulthood and old age.

PMID- 29171960
TI  - Longitudinal trajectories of subjective care stressors: the role of personal,
      dyadic, and family resources.
AB  - OBJECTIVES: Stressors are critical to the caregiver stress process, yet little
      work has examined resources that contribute to longitudinal changes in subjective
      stressors. The present study examines a variety of factors that contribute to
      changes in subjective stressors across time. METHOD: Dementia caregivers (N =
      153) completed an in-person interview and eight daily telephone interviews at
      baseline, and follow up interviews at 6 and 12 months. Growth curve analyses
      examine how care- and non-care stressors, respite, dyadic relationship quality,
      family support/conflict and care transitions (e.g. nursing home placement) are
      associated with changes in role overload and role captivity across 12 months.
      RESULTS: Caregivers who transitioned out of their role had higher overload and
      captivity at baseline. Among caregivers who transitioned out of caregiving,
      higher captivity at baseline was associated with declines in captivity and
      overload; more non-care stressors at baseline was linked to increased captivity
      and greater overload across time. Adult day service use and family support were
      associated with lesser captivity over time; taking more breaks from caregiving
      was linked to lower overload. Higher dyadic relationship quality was associated
      with lower captivity and overload. CONCLUSION: Findings contribute to caregiver
      intervention efforts by highlighting important resources associated with
      subjective stressors across time.

PMID- 29171961
TI  - Social impact of menstrual problems among adolescent school girls in rural Tamil
      Nadu.
AB  - Background Adolescence is a period of physiological, psychological and social
      transition between childhood and adulthood and is characterized by the onset of
      menstruation in girls. A adolescent girls are naive about menstruation and they
      take time to adapt to these changes both socially and psychologically. This study
      was carried out to assess the psychosocial impact of menstrual problems among
      schoolgoing adolescent girls. Methods This study is a cross-sectional study
      carried out in 350 schoolgoing adolescent girls in the year 2012 in the
      Thiruvallur district of Tamil Nadu. Girls who attained menarche 1 year prior to
      the data collection were included in the study. Data regarding background
      characteristics and psychosocial impact of menstrual problems were collected.
      Data was analyzed using SPSS ver. 15 software. The chi2-test was carried out to
      assess the statistical significance at the 95% level of significance. Results The
      mean age of the participants was 14.7 years. In this study, 87.7% of the girls
      had at least one menstrual problem. Among these, 78.5% could not attend school
      during menstruation, 51.1% were unable to perform household/sports activities (p
      < 0.001). It was observed that dysmenorrhea and menorrhagia were at increased
      risk of absenting the girls from school (p < 0.05). Conclusion The key to a sound
      adolescent health programme is a holistic approach which also focuses on the
      psychological and social domain of health. This could be achieved by involving
      all the stakeholders like parents, teachers, etc. to work as a team. It is also
      essential to develop adolescent friendly health services at the grass root level.

PMID- 29171962
TI  - Maternal demographic factors associated with emergency caesarean section for non
      reassuring foetal status.
AB  - OBJECTIVES: This study aimed to determine maternal and obstetric factors
      associated with emergency caesarean section (CS) for non-reassuring foetal status
      (NRFS). MATERIALS AND METHODS: This was a retrospective analysis of term
      singleton births between January 2007 and December 2015 at the Mater Mother's
      Hospital in Brisbane. The study group comprised all cases of emergency CS for
      NRFS, and the control cohort comprised all other births meeting the inclusion
      criteria but excluding those in the study cohort. RESULTS: Over the study period,
      there were 74,177 births fulfilling the inclusion criteria. The overall rate of
      emergency CS for NRFS was 4.2% (3132/74,177). Multivariate analysis showed that
      being overweight and obese, Indian and "other" ethnicity, artificial reproductive
      techniques, smoking, induction of labour and gestation at 39-42 weeks were
      associated with an increased risk, whereas being underweight, female sex,
      hypertension and birth without labour conferred a lower risk. CONCLUSION: Many
      maternal and obstetric factors were associated with emergency CS for NRFS and
      influenced adverse perinatal outcomes. Recognition of these risk factors could
      help risk stratify women prior to labour.

PMID- 29171963
TI  - Indium selenide monolayer: strain-enhanced optoelectronic response and dielectric
      environment-tunable 2D exciton features.
AB  - Electronic and optical performances of the beta-InSe monolayer (ML) are
      considerably boosted by tuning the corresponding band energies through lattice in
      plane compressive strain engineering. First principles calculations show an
      indirect-direct gap transition with a large bandgap size. The crossover is due to
      different responses of the near-gap state energies with respect to strain. This
      is explained by the variation of In-Se bond length, the bond nature of near-band
      edge electronic orbital and of the momentum angular contribution versus in-plane
      compressive strain. The effective masses of charge carriers are also found to be
      highly modulated and significantly light at the indirect-direct-gap transition.
      The tuned optical response of the resulting direct-gap ML beta-InSe is evaluated
      versus applied energy to infer the allowed optical transitions, dielectric
      constants, semiconductor-metal behavior and refractive index. The environmental
      dielectric engineering of exciton behavior of the resulting direct-gap ML beta
      InSe is handled within the effective mass Wannier-Mott model and is expected to
      be important. Our results highlight the increase of binding energy and red
      shifted exciton energy with decreasing screening substrates, resulting in a
      stable exciton at room temperature. The intensity and energy of the ground-state
      exciton emission are expected to be strongly influenced under substrate screening
      effect. According to our findings, the direct-gap ML beta-InSe assures tremendous
      2D optoelectronic and nanoelectronic merits that could overcome several
      limitations of unstrained ML beta-InSe.

PMID- 29171964
TI  - First site of recurrence after breast cancer adjuvant treatment in the era of
      multimodality therapy: which imaging for which patient during follow-up?
AB  - PURPOSE: We evaluated the relation between first site of recurrence of early
      breast cancer and disease profile at presentation and reported survival results,
      suggesting a personalized diagnostic imaging guidance during follow up. METHODS:
      Among 1400 early breast cancer treated from 2000 to 2010, 324 relapses were
      divided into 4 groups according to first site: A-locoregional, B-bone, C-Brain
      and D-visceral. We analyzed redictive factors of each group compared to a control
      group of 100 non relapsing patients and the remaining groups matched. RESULTS: In
      group A, patients were more likely to have histological tumor size above >2 cm,
      grade 1-2, HR positive and 0-3 involved lymph nodes. In group B, patients had
      more commonly grade 2-3, 1-3 positive lymph nodes and HR positive tumors. In
      group C, patients were more frequently young, with large tumor size, grade3,
      positive lymph nodes and HER2 positive tumors. In group D, patients were more
      likely to have tumors>2 cm in size, with nodal involvement, grade 3, HR negative
      and HER2 positive tumors. Annual recurrence rate in group A, was stable ranging
      between 15%-18%, within the first 3 years and peaked at 19.4% in the interval [1
      2]year in group B. Median survival was 46 months in group A, 43 months in group
      B, with no significant difference. CONCLUSION: Outcome of loco-regional and bone
      relapses was good, suggesting that both systematic mammography and bone-scan/CT
      scan for high risk patients (N+, gradeIII) during the first 2-3 years may
      represent a tailored relevant follow-up protocol for breast cancer patients.

PMID- 29171965
TI  - Fibrotic infarction on the LV free wall may alter the mechanics of healthy septal
      wall during passive filling.
AB  - The effect of myocardial infarction on the global functioning of the heart is
      well known. Less is understood regarding the effect of LV fibrotic infarction on
      the cardiac mechanics of the septal wall. To determine this unknown, the stress
      and strain of septal wall on the healthy and infarcted rat heart model is
      measured by using finite element models of rat heart geometries. The main
      objective of this study was to utilized computational methods to study the effect
      of LV free wall fibrotic infarction on the healthy septal wall. Three-dimensional
      biventricular rat heart geometries were developed from cardiac magnetic resonance
      images of a healthy heart and a heart with left ventricular (LV) fibrotic
      infarction after infarct induction. From these geometries, FE models were
      established. Three-dimensional biventricular rat heart geometries developed from
      cardiac magnetic resonance images were used in creating FE models of healthy and
      infarcted rat hearts. The average radial strain percentage change of the healthy
      septal wall on the epicardium, mid-wall and endocardium was 61%, 52% and 14%
      higher than the infarcted septal wall, respectively. It was concluded that the
      fibrotic infarction has a potential cause the malfunction of the heart due to
      high myocardial stress and strain that the septal wall experiences.

PMID- 29171966
TI  - Feasibility research of non-invasive methods for interstitial fluid level
      measurement.
AB  - This article explores a non-invasive method to determine interstitial fluid level
      and pressure in tissue. Interdigital electrodes were chosen by simulated results
      in software "Comsol multiphysis 4.3a". Environment model similar to human body
      was created. Measurements were carried out at different situations which can
      occur during preoperative and afterwards surgery. Non-invasive method decreases
      possibility of infection and will improve recovery process in postoperative
      period.

PMID- 29171967
TI  - Surface characteristics of three commercially available grafts and adhesion of
      stem cells to these grafts.
AB  - BACKGROUND: Reconstruction of bone defects is often performed using bone
      autografts. However, limitations associated with the use of autografts led to the
      use of bone substitute materials. OBJECTIVES: The purpose of this study was to
      compare the surface characteristics of three commercially available grafts namely
      allografts, xenografts and alloplasts. METHODS: This in vitro study was conducted
      on beta-tricalcium phosphate (beta-TCP) alloplast, a mixture of demineralized
      bone matrix and mineralized bone allograft (DBM&MBA) and natural bovine bone
      mineral (NBBM) xenograft. Presence of apatite groups on the surface of samples
      was assessed by X-ray diffraction (XRD) while the presence of functional groups
      was evaluated using Fourier transform infrared spectroscopy (FTIR). Also, dental
      pulp stem cells (DPSCs) were cultured on the surface of samples and their
      adhesion was evaluated under a scanning electron microscope (SEM). RESULTS: The
      FTIR showed a relatively similar pattern for NBBM and TCP samples and a different
      pattern in DBM&MBA. The results of XRD analysis also showed similarities between
      NBBM and TCP with sharper peaks than the DBM&MBA sample. The SEM micrographs
      showed that at 24 hours, no cell was detectable on the surface of NBBM sample;
      whereas, elongated cells were noted on the surface of TCP and DBM&MBA samples.
      CONCLUSIONS: The patterns of beta-TCP and NBBM samples in XRD and FTIR
      spectroscopy showed high resemblance but they had different behaviors with
      respect to cell adhesion.

PMID- 29171968
TI  - Effects of Uygur sand therapy on the mechanical properties of femurs in
      osteoarthritic rabbits.
AB  - OBJECTIVE: To investigate the effects of Uygur sand therapy on the mechanical
      properties of the femur bone of osteoarthritic rabbits. METHODS: Sixteen rabbits
      were injected with papain in the right posterior femoral articular cavity on the
      first, fourth and seventh day to establish the osteoarthritis (OA) rabbit model.
      Animals were divided into the experimental group and control group (8 rabbits
      each). The experimental group was treated with sand therapy, and the control
      group received no sand therapy treatment. Computed tomography (CT) scanning was
      used to collect the data of the femur before modeling, after modeling and 14 and
      28 days after sand treatment. A 3D model of the femur was generated with the
      MIMIC software the bone layer was divided according to the different gray values
      and the change of the bone volume was analyzed. The body mesh is divided, and the
      material properties are given, then the three-point bending simulation is
      performed in Ansys. Additionally, the three-point bending test was performed on
      all the rabbits' femur to obtain the deflection and maximum stress values. And
      the effects of the sand treatment on the volume and mechanical properties of the
      bone were analyzed. Finally, the simulation results are compared with the
      experimental results, and the effects of sand treatment on the volume and
      mechanical properties of the bone are analyzed. RESULTS: (1) there is a tendency
      in the control group to convert the hard bone into dense bone and soft bone,
      while in the experimental group, the soft bone is converted into dense bone and
      hard bone obviously; (2) the morphological parameters of the experimental group
      are lower than those of the control group, whereas the maximum load, maximum
      normal stress, maximum shear stress of the experimental group are higher than
      those of the control group. (3) The mechanical test of three-point bending test
      was carried out using the three dimensional finite element model of rabbit femur.
      CONCLUSION: The sand therapy has positive effects on the volume distribution of
      bone layer and the mechanical properties of the femur of adult osteoarthritic
      rabbits.

PMID- 29171969
TI  - Teaching learning based optimization-functional link artificial neural network
      filter for mixed noise reduction from magnetic resonance image.
AB  - BACKGROUND: The clinical magnetic resonance imaging (MRI) images may get
      corrupted due to the presence of the mixture of different types of noises such as
      Rician, Gaussian, impulse, etc. Most of the available filtering algorithms are
      noise specific, linear, and non-adaptive. OBJECTIVE: There is a need to develop a
      nonlinear adaptive filter that adapts itself according to the requirement and
      effectively applied for suppression of mixed noise from different MRI images.
      METHODS: In view of this, a novel nonlinear neural network based adaptive filter
      i.e. functional link artificial neural network (FLANN) whose weights are trained
      by a recently developed derivative free meta-heuristic technique i.e. teaching
      learning based optimization (TLBO) is proposed and implemented. RESULTS: The
      performance of the proposed filter is compared with five other adaptive filters
      and analyzed by considering quantitative metrics and evaluating the nonparametric
      statistical test. The convergence curve and computational time are also included
      for investigating the efficiency of the proposed as well as competitive filters.
      CONCLUSION: The simulation outcomes of proposed filter outperform the other
      adaptive filters. The proposed filter can be hybridized with other evolutionary
      technique and utilized for removing different noise and artifacts from others
      medical images more competently.

PMID- 29171970
TI  - Bone regeneration from human mesenchymal stem cells on porous hydroxyapatite-PLGA
      collagen bioactive polymer scaffolds.
AB  - We have developed a novel multicomponent nano-hydroxyapatite-poly(D,L-lactide-co
      glycolide)-collagen biomaterial (nHAP-PLGA-collagen) with mechanical properties
      similar to human cancellous bone. To demonstrate the bone forming capacity of
      nHAP-PLGA-collagen prior to in vivo experiments, nHAP-PLGA-collagen films and 3D
      porous scaffolds were seeded with human mesenchymal stem cells (hMSCs) to
      characterize cell proliferation and osteogenic differentiation. Over 21 days
      hMSCs seeded on 2D nHAP-PLGA-collagen films proliferate, form nodules, deposit
      mineral and express high alkaline phosphatase activity (ALP) indicating
      commitment of hMSCs towards osteogenic lineage. When seeded in 3D scaffolds,
      hMSCs migrate throughout the connected porous network of the nHAP-PLGA-collagen
      scaffold and proliferate to fill the scaffold voids. Over 35 days, cells express
      ALP, osteocalcin and deposit minerals with kinetics similar to osteogenesis in
      vivo. Adipogenic or chondrogenic differentiation is not detected in 3D
      constructs, indicating that in an osteogenic environment the presence of bone ECM
      specific molecules in nHAP-PLGA-collagen scaffolds support homogeneous bone
      tissue development. This ability of nHAP-PLGA-collagen matrices to provide
      biochemical stimulation to support osteogenesis from stem cells along with its
      high mechanical strength suggests that nHAP-PLGA-collagen is a suitable
      biomaterial for bone regeneration. This platform technology of covalently
      attaching ECM proteins and molecules with synthetic and natural polymers to
      adjust material properties and biochemical signaling has a potential for a wider
      range of applications in tissue engineering and regenerative medicine.

PMID- 29171971
TI  - A method for systematically evaluating the hemostatic ability of hydrogels in
      vitro.
AB  - The bursting strength is a key parameter to assess hemostatic ability of tissue
      sealants. It is associated to mechanical property of the materials, the binding
      strength of the materials to the tissues as well as the applied conditions of the
      materials, such as temperature and wound size. Few works have systematically
      investigated the relationship of the hemostatic ability of hydrogels with the
      factors listed above. This study introduced a method to systematically
      investigate the effect of the thickness, covered area and components of
      hydrogels, and the applied conditions on the bursting strength of hydrogels. The
      gelatin hydrogel and fibrin glue were used in this study. The method
      quantitatively investigated the effect of material properties and applied
      conditions on the bursting strength of materials. It also suggested a minimum
      dosage of tissue sealant used in both animal study and clinical practice. This
      study proved that the method we proposed is reliable to assess the bursting
      strength of materials for the hemostatic application.

PMID- 29171972
TI  - Different methods to determine the encapsulation efficiency of protein in PLGA
      nanoparticles.
AB  - BACKGROUND: Effective encapsulation of drugs into the delivery systems could
      increase the efficiency of nanoparticles in prevention and treatment of diseases.
      OBJECTIVE: The purpose of this study was to compare the different methods for
      determination of encapsulation efficiency of a model protein in the PLGA
      nanoparticles. METHODS: The various direct methods include dichloromethane,
      acetonitrile, modified acetonitrile and NaOH based extraction and radioactive
      methods were used to directly calculate the encapsulation efficiency of the
      loaded protein in the PLGA nanoparticles. Furthermore, indirect methods include
      BCA, Fluorescent and radioactive methods were compared. RESULTS: The
      encapsulation efficiencies determined by indirect methods include
      dichloromethane, acetonitrile, modified acetonitrile, NaOH based extraction and
      radioactive methods were 12.62% +/- 1.97, 17.43% +/- 2.51, 64.69% +/- 4.31,
      86.36% +/- 2.25 and 90.15% +/- 1.78, respectively. Moreover, the encapsulation
      efficiencies determined by indirect methods include BCA, fluorescent and
      radioactive methods were 81.46% +/- 1.92, 88.23% +/- 1.15 and 89.6% +/- 1.9,
      respectively. CONCLUSIONS: Among the results obtained by indirect methods,
      radioactive and fluorescent methods showed more reliable. Moreover, NaOH and
      radioactive methods were the most reliable methods among the direct methods.

PMID- 29171973
TI  - Biocompatibility evaluation and corrosion resistance of tungsten added Co-30Cr
      4Mo-1Ni alloy.
AB  - Biomaterials are continuously being developed to overcome the drawbacks of
      existing materials and provide improved function in artificial organs. Currently
      Co-Cr based alloys are used in many medical applications such as hip and knee
      implants which still require modification to better perform. In this article,
      therefore, the influence of tungsten allying element on electrochemical corrosion
      resistance and biocompatibility behaviour of a recently developed Co-30Cr-4Mo-1Ni
      alloy composition were investigated. The tungsten modified alloys were prepared
      by using a high temperature vertical vacuum casting technique at five different
      weight percentages (0-4wt.% tungsten). The electrochemical corrosion behaviour of
      all the samples under NaCl solution was studied by using potentiodynamic scan
      method. The corrosion characteristics were investigated in terms of corrosion
      potential (Ecorr) and corrosion current density (Icorr). From the results of the
      analysis, it was observed that out of all samples, an alloy with 2wt.% of
      tungsten in composition (i.e. Co-30Cr-4Mo-1Ni-2W) exhibited better corrosion
      resistance. Furthermore, histopathological evaluations in subcutaneous tissue
      were performed in rats according to the standard ISO 10993 to examine the
      biocompatibility of the prepared samples. The results showed no evidence of
      inflammatory cell migration, no epidermal necrosis, no vacuolar degeneration of
      basal cell, no adnexal atrophy and vesicle formation of any samples. The obtained
      findings indicate that Co-30Cr-4Mo-1Ni-2W can be used in biomedical applications
      including femoral component of hip and knee implants.

PMID- 29171975
TI  - An unusual coexistence of lymphedema with myotonic dystropy: The effect of
      complex decongestive therapy.

PMID- 29171974
TI  - Co-existence effect of tricalcium phosphate and bioactive glass on biological and
      biodegradation characteristic of Poly L-Lactic Acid (PLLA) in trinary composite
      scaffold form.
AB  - The purpose of this study is to analyze the co-existence effect of 30 wt.% TCP-BG
      phases on degradation and precipitation behaviors of PLLA based composite
      scaffold in biological media. First, phase separation method was used to
      synthesize of the pure PLLA and the trinary composite scaffolds, and second they
      were immersed in SBF solution for 45 days. Subsequently, the degradation and
      precipitation characteristic were investigated by analyzing of pH value and
      weight changes of the immersed samples, the ability of biological products
      formation and the change of relative molecular weight of PLLA matrix as function
      of the degradation time. Finally, the experimental data of relative molecular
      weight change were verified by Han and Pan model and comparisons were made
      between them. Results have represented precipitation of huge amount of carbonate
      apatite on surface of the composite scaffold, and also the acidity of SBF media
      changes moderately which is prove better bioactivity properties compare to the
      pure PLLA scaffold. The results of comparison with the model point to quiet good
      agreement between them in early stage of degradation. So, the consequences
      suggest that the TCP-BG/PLLA composite scaffold have great potential to be
      applied in bone replacements or repairs.

PMID- 29171976
TI  - Right versus left side bridge static endurance ability among healthy collegiate
      students at Taibah University.
AB  - BACKGROUND: Spinal muscles endurance is fundamental for providing adequate trunk
      stability. OBJECTIVE: The purpose of this study was to compare the side bridge
      static endurance ability of the right versus left side. METHODS: Forty right hand
      dominant students, aged between 18 and 25 years, were recruited from Taibah
      University. Every participant had to lie down on his side and bear trunk weight
      on the arm with shoulder abducted to 90? and elbow flexed to 90?. Every
      participant had to lift off his trunk of the supporting surface, keeping the
      trunk straight in neutral position, breathing normally and holding on that
      position as long as tolerated. RESULTS: A paired sample t test was calculated.
      The mean score, in seconds, for right side bridge was 41.6 (SD = 30.08), and for
      left side bridge was 38.00 (SD = 26.93). No significant difference was found
      between right and left side bridge endurance ability [t (39) = 1.67, p> 0.05].
      Pearson correlation showed high positive correlation [r (38) = 0.89, p< 0.001].
      CONCLUSIONS: Among healthy participants, clinicians should expect very close
      endurance profile for the musculature of the two sides of trunk. Clinicians
      should equally train both sides of trunk muscles stabilizers in order to enhance
      tolerance.

PMID- 29171977
TI  - Ultrasonographic measurements of the metacarpophalangeal and talar cartilage
      thicknesses: A reliability study in healthy subjects.
AB  - BACKGROUND: Assessment of the joint cartilage using ultrasound imaging is
      important. OBJECTIVE: Our aim was to investigate the reliabilities of
      ultrasonographic measurements for talus dome (TCT) and metacarpal cartilage
      thicknesses (MCT). METHODS: Twenty healthy volunteers were recruited in the
      study. Every day, five physiatrists measured eight joint cartilage thicknesses.
      They repeated all the measurements in five consecutive days. RESULTS: Intra
      observer intraclass correlation coefficient (ICC) values were "excellent" for all
      MCTs, except for the 3rd left MCT on the 1st day, 4th left MCT on the 1st day and
      4th right MCT on the 3rd day which were "good". They were "excellent" for the TCT
      measurements, except for the left side on the 3rd day and the right side on the
      4th day which were "good". Inter-observer ICC values pertaining to the 2nd MCT
      measurements were "excellent" for all sonographers. Third and 4th MCT
      measurements (at least one side) were "excellent" for four and three
      sonographers, respectively. On the other hand, while TCT measurements were
      "excellent" for 4 sonographers. CONCLUSIONS: Our results have shown that
      sonographic measurements of MCT and TCT have good to excellent reliabilities in
      healthy adults. These findings support the use of ultrasound for cartilage
      assessment in various diseases.

PMID- 29171978
TI  - Comparison between zero-profile spacer and plate with cage in the treatment of
      single level cervical spondylosis.
AB  - BACKGROUND: Retrospective study of 68 patients of symptomatic cervical
      spondylosis who were treated by anterior cervical discectomy and fusion (ACDF).
      OBJECTIVE: The purpose of this study was to compare the clinical and radiological
      outcomes of patients with single level cervical spondylosis using either zero
      profile spacer (group A) or anterior cervical plate and cage (group B). METHODS:
      Clinical and radiological data of 68 patients undergoing ACDF from C3-C7 were
      collected retrospectively. There were 35 patients with a mean age of 54.05 years
      who received treatment by zero-profile implant. A total of 33 patients with a
      mean age of 52.09 years underwent fusion by traditional plate with cage. Group A
      and group B were followed up for an average of 23.68 months and 24.39 months,
      respectively. Age, blood loss, and operation time were assessed. The clinical
      outcomes were evaluated by JOA and VAS score before and after surgery. In
      addition, incidence of dysphagia was recorded. The Cobb angle (from C2 to C7)
      change was measured on the lateral cervical spine radiographs. RESULTS: There was
      no significant difference in terms of operation time and blood loss between two
      groups. The postoperative JOA significantly increased and the VAS decreased
      correspondently in both groups. The postoperative Cobb angle increased and showed
      statistical difference compared with preoperative Cobb angle in both groups.
      There was no significant difference between group A and group B in achieving
      clinical symptoms and radiograph improvement according to postoperative JOA, VAS
      and Cobb angle comparison. The incidence of postoperative dysphagia was lower in
      the group A than group B. CONCLUSIONS: Our study suggests that the application of
      zero-p spacer can achieve similar clinical and radiological improvement compared
      with traditional plate and cage. Meanwhile, zero-p is superior to plate and cage
      with a lower incidence of postoperative dysphagia.

PMID- 29171979
TI  - Influence of a dynamic seating habit on lumbar motor control in schoolchildren.
AB  - BACKGROUND: Adequate motor control is considered important for spinal stability
      and the prevention of low back pain in adulthood and in childhood. OBJECTIVE:
      Given that the sitting position can affect proprioception, this study aimed to
      evaluate the influence of using at school a triangular and dynamic cushion on
      schoolchildren's trunk motor control. METHODS: Thirty 8-year-old schoolchildren
      were randomized into a control group (n= 15) and a "cushion group" (n= 15), in
      which the children used the cushion for one year and a half. At the end of this
      period, a 3D-analysis was used to assess lumbar spine proprioception by means of
      a trunk repositioning task performed blindfolded in a seated position in two
      conditions (on a stable and on an unstable surface). RESULTS: The schoolchildren
      in the cushion group performed better at the trunk repositioning task (p= 0.02)
      and hold their lumbar lordosis (p= 0.03) better than the control children, in
      both conditions (stable and unstable). CONCLUSIONS: This preliminary study
      suggests that daily use of a triangular dynamic cushion has a beneficial impact
      on children's lumbar proprioception. Further studies are needed to confirm these
      results and investigate the effectiveness of its use to prevent low back pain in
      adulthood.

PMID- 29171980
TI  - Effectiveness of Neuro-Developmental Treatment (Bobath Concept) on postural
      control and balance in Cerebral Palsied children.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to show the effects of an 8
      week Neurodevelopmental Treatment based posture and balance training on postural
      control and balance in diparetic and hemiparetic Cerebral Palsied children (CPC).
      METHODS: Fifteen CPC (aged 5-15 yrs) were recruited from Denizli Yagmur Cocuklari
      Rehabilitation Centre. Gross Motor Function Classification System, Gross Motor
      Function Measure, 1-Min Walking Test, Modified Timed Up and Go Test, Paediatric
      Balance Scale, Functional Independence Measure for Children and Seated Postural
      Control Measure were used for assessment before and after treatment. An 8-week
      NDT based posture and balance training was applied to the CPC in one session (60
      min) 2 days in a week. RESULTS: After the treatment program, all participants
      showed statistically significant improvements in terms of gross motor function
      (p< 0.05). They also showed statistically significant improvements about balance
      abilities and independence in terms of daily living activities (p< 0.05). Seated
      Postural Control Measure scores increased after the treatment program (p< 0.05).
      CONCLUSIONS: The results of this study indicate that an 8-week Neurodevelopmental
      Treatment based posture and balance training is an effective approach in order to
      improve functional motor level and functional independency by improving postural
      control and balance in diparetic and hemiparetic CPC.

PMID- 29171981
TI  - A comparison of occupational groups using different working postures in terms of
      their low back and neck health status.
AB  - OBJECTIVE: To compare how disability, fear of movement, psychosocial status and
      quality of life are affected in terms of low back-neck health status in three
      occupational groups using different work postures. METHOD: Three hundred thirty
      nine individuals participated in this study from the following three different
      occupational groups: group A, where the individuals worked in a prolonged sitting
      position (secretaries), group B, where the individuals performed dynamic
      activities in a standing position (cleaning workers) and group C, where the
      individuals worked in a prolonged standing position (private security officers).
      The participants were evaluated by Million Visual Analog Scale, Neck Disability
      Index, Oswestry Disability Index, Nottingham Health Profile, Hospital Anxiety and
      Depression Scale and Tampa Kinesiophobia Scale. RESULTS: It was found that
      disability, emotional status and the quality of life were minimally affected, but
      kinesiophobia was increased in all of the occupational groups. In the group C,
      low back pain disability, quality of life and fear of movement were more affected
      than the other groups (p< 0.05). CONCLUSION: For the occupational groups with
      long working years, the presence of kinesiophobia should be considered and
      cognitive-behavioural treatment methods should be recommended. In cleaning
      workers, low back pain is an important risk factor. Therefore, its awareness
      should be increased, and preventive programmes should be offered.

PMID- 29171982
TI  - Morphofunctional muscle changes influence on foot stability in multiple sclerosis
      during gait prediction: The rehabilitation potential.
AB  - BACKGROUND: Multiple sclerosis patients may suffer muscle changes that involve
      gait disorders of the kinetic and kinematic parameters also their gait may be
      clinically symmetrical or asymmetrical. OBJECTIVE: The aim of this study is to
      analyze how the muscle change, could affect the biomechanical parameters of foot
      stability during the gait, by disturb the motor control. METHODS: The study group
      consisted of 13 patients diagnosed with multiple sclerosis, presenting clinically
      detectable abnormal gait. The biomechanical evaluation included the foot axes and
      angles -external and internal rotation; the foot angle deviation from the gait
      direction; the subtalar angle. RESULTS: The values of the foot angle were between
      -10.74? to 26.38? for the left foot and between -11.16? to 30.04? for the right
      foot. The foot axis angle is the axis of the foot in relation to the gait
      direction, and the subtalar angle is in relation to the vertical axis of the
      foot. The rotation of the right foot into pronation during the initial contact
      phase was followed by supination in the semi-support phase, to return to the
      neutral position during the propulsion phase, which meant being in free zone of
      minimal risk. CONCLUSIONS: Biomechanical analysis of the foot angle and of
      subtalar angle in the patients with multiple sclerosis allows us to objectify the
      existence of a right-left asymmetry, the behavior ankle-foot during the gait. At
      the same time this evolution is closely correlated with the contact surface that
      tends to increase, which means involving the reflex mechanisms that place the
      foot in the zone of minimum risk and assure the stability of the body.

PMID- 29171983
TI  - Growth differentiation factor (GDF-15) concentration combined with Ca125 levels
      in serum is superior to commonly used cancer biomarkers in differentiation of
      pancreatic mass.
AB  - BACKGROUND: Pancreatic cancer (PDAC) will have been the second leading cancer
      related death in the United States by 2020, according to current estimation. Its
      late manifestation and the lack of good early detection methods are the cause of
      extremely low survival rates. Therefore, there is an urgent need to develop
      highly sensitive and specific marker. GDF-15, a member of TGFbeta family, has
      recently emerged as a protein playing an important role in carcinogenesis of
      various neoplasms. OBJECTIVE: Our aim was to assess the potential of GDF-15, IL
      17, IL-23 serum concentration, and the panel of PDAC markers in differentiating
      pancreatic adenocarcinoma from chronic pancreatitis. METHODS: Sixty-three
      consecutive patients operated on due to pancreatobiliary lesions were enrolled in
      this study. Levels of CEA, CA125 and Ca19-9 were assessed using standard
      laboratory protocols. A sample of serum was collected prior to the surgery via
      central line. Levels of GDF-15, Il-17, Il-23 were measured using a ELISA kit.
      After standard pathological examination of specimens obtained on surgery,
      patients were divided into 2 groups: 42 patients with pancreatic adenocarcinoma
      and 21 patients with focal chronic pancreatitis. RESULTS: Mean GDF-15
      concentration in patients with CP vs PDAC was 2247.95 (+/- 179.27) vs 7694.58 (+/
      1878.94) [pg/mL] respectively (p= 0.011). Mean concentration of Il-17, Il-23,
      Ca19-9, Ca125, Ca15-3, CEA in patients with CP and PDAC was 862.36 (+/- 30.84) vs
      841.83 (+/- 33.94) p= 0.833; 127.85 (+/- 5.87) vs 127.51 (+/- 9.74) p= 0.175;
      34.95 (+/- 23.34) vs 266.62 (+/- 49.7) p= 0.001; 13.4 (+/- 1.6) vs 39.27 (+/-
      6.85) p= 0.005; 18.4 (+/- 1.48) vs 20.2 (+/- 1.38) p= 0.416; 1.96 (+/- 0.38) vs
      5.93 (+/- 1.74) p= 0.004 respectively. In order to compare these markers with the
      routinely used ones, ROC curve was built. CA19-9 with clinically used cut-off
      point of ? 36 IU/mL has specificity of 90.5% and sensitivity of 57.14%. At the
      same time GDF-15 with the optimal cut-off point of 2.7 ng/mL has specificity of
      76.19% and sensitivity of 73.8%. Although in our research group CA19-9 has an
      excellent specificity, its usefulness is hampered by its low sensitivity. On the
      other hand, GDF-15 parameters are well-balanced making it a more useful biomarker
      of PDAC. CONCLUSIONS: In conclusion, GDF-15 is more accurate than Ca19-9 in
      differentiating pancreatic mass due to chronic pancreatitis from pancreatic
      adenocarcinoma. Interleukin 17 and 23 cannot be considered as PDAC biomarkers.
      GDF-15 concentration in serum should be further investigated in order to assess
      their usefulness in pancreatic adenocarcinoma diagnosis.

PMID- 29171984
TI  - MicroRNA-1246 inhibits cell invasion and epithelial mesenchymal transition
      process by targeting CXCR4 in lung cancer cells.
AB  - BACKGROUND: Recent studies have indicated that microRNAs (miRNAs) are closely
      related to lung cancer. However, the effects of miR-1246 on lung cancer are still
      elusive. In this study, we aimed to explore the molecular mechanisms of miR-1246
      in lung cancer. MATERIALS AND METHODS: Using RT-qPCR assay, we analyzed the
      expression of miR-1246 in lung cancer cell lines and lung epithelial cell line.
      Using Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell, RT-qPCR and western
      blot assays, we investigated cell viability, apoptosis, invasion and epithelial
      mesenchymal transition (EMT) process. Using luciferase reporter assay, we
      confirmed a target of miR-1246. Using western blot assay, we detected the protein
      mechanisms of Janus kinase (JAK)/signal transducer and activator of transcription
      (STAT) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signal
      pathways. RESULTS: Our results showed that miR-1246 was down-regulated in lung
      cancer cell lines (A549, H1650 and H1299) compared to in lung epithelial cell
      line (16HBE14o). MiR-1246 overexpression remarkably inhibited cell invasion as
      well as up-regulated E-cadherin expression and down-regulated N-cadherin,
      Vimentin, ZEB1 and Snail expressions in A549 cells. Further studies have
      confirmed CXCR4 as a target gene of miR-1246, and CXCR4 silence significantly
      abolished the promotion effect of miR-1246 suppression on cell invasion and EMT
      process in A549 cells. Besides, miR-1246 blocked JAK/STAT and PI3K/AKT signal
      pathways by regulation of CXCR4. CONCLUSIONS: These results demonstrated that miR
      1246 inhibited cell invasion and EMT process by targeting CXCR4 and blocking
      JAK/STAT and PI3K/AKT signal pathways in lung cancer cells.

PMID- 29171985
TI  - Low-level serum miR-24-2 is associated with the progression of colorectal cancer.
AB  - BACKGROUND: colorectal cancer (CRC) is the second leading cause of cancer and
      cancer-related death in the world. Noninvasive biomarkers for early diagnosis of
      CRC are highly demanded. OBJECTIVE: The up-regulation of specific microRNAs
      (miRNAs) in serum has been considered a promising biomarker of CRC and miR-24-2
      may be a potential biomarker in the diagnosis the progression of CRC. METHODS:
      Sixty-eighty healthy subjects and 228 CRC patients were divided into six groups:
      control group, CRC 0, CRC I, CRC II, CRC III, CRC IV and CRC V. Serum level of
      miR-24-2 was measured by real-time qPCR. Serum lipid profiles and oxidative
      related molecules were also measured. RESULTS: Serum levels of miR-24-2 in CRC
      patients were significantly higher than healthy subjects (p< 0.05). In addition,
      the expression level of the miR-24-2 was decreased with the progression of CRC
      and reached the lowest level in CRC V. Spearman Rank Correlation analysis showed
      that miR-24-2 level was negatively related to the levels of superoxide dismutase
      (SOD) and reduced glutathione (GSH), aspartate transaminase (AST), alanine
      transaminase (ALT), cholesterol and triglyceride (p< 0.05). CONCLUSIONS: Serum
      miR-24-2 is a potential negative biomarker in the diagnosis of the progression of
      CRC patients and associated with biochemical indices.

PMID- 29171986
TI  - Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic
      features and prognosis of ovarian cancer.
AB  - OBJECTIVE: To explore the correlation of PD-1/PD-L1 polymorphisms and their
      expressions with clinicopathologic features and prognosis of ovarian cancer.
      METHODS: A total of 164 patients with ovarian cancer were enrolled as case group
      and 170 healthy women as control group. We conducted quantitative reverse
      transcription-PCR (qRT-PCR) to determine PD-1/PD-L1 expressions in peripheral
      blood mononuclear cells (PBMCs). Polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) and allele-specific amplification were used to
      detect PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G. RESULTS: PD-1 rs2227982 C>T
      and PD-L1 rs4143815 C>G polymorphisms increased the risk for ovarian cancer. PD-1
      rs2227982 C>T was associated with FIGO stage and differentiation grade, while PD
      L1 rs4143815 C>G was correlated with histological type and differentiation grade.
      Besides, PD-1/PD-L1 expressions were positively correlated in PBMCs of patients
      with ovarian cancer to be associated with differentiation grade. Compared with
      wild homozygous patients, PD-1/PD-L1 expressions were significantly decreased in
      PBMCs of ovarian cancer patients carried with the mutant genotypes of rs2227982
      C>T and rs4143815 C>G. The PFS and OS in ovarian cancer patients with wild
      homozygous genotype of rs2227982 C>T and rs4143815 C>G were significantly higher
      than those with mutant genotypes, which were significantly lower in patients with
      low expressions of PD-1/PD-L1 than those with high expressions. Univariate COX
      regression analysis identified FIGO staging, differentiation grade, rs2227982
      C>T, rs4143815 C>G and expressions of PD-1/PD-L1 as the prognostic factors, and
      multivariate COX regression analysis demonstrated that high FIGO stage and low
      expressions of PD-1/PD-L1 were independent risk factors for the prognosis of
      ovarian cancer. CONCLUSION: PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G
      polymorphisms increased the risk of ovarian cancer, leading to a poor prognosis,
      associated with low expressions of PD-1 and PD-L1. While high PD-1 and PD-L1
      expressions are indicators of a favorable prognosis in ovarian cancer.

PMID- 29171987
TI  - Dysregulation of miR-126/Crk protein axis predicts poor prognosis in gastric
      cancer patients.
AB  - BACKGROUND: miR-126 functions as a tumor suppressor in gastric cancer (GC) by
      negatively regulating Crk protein expression post-transcriptionally. OBJECTIVE:
      The aim of this study was to investigate the associations of miR-126 and Crk
      protein expression levels, alone or in combination, with the clinicopathological
      characteristics and prognosis of GC patients. METHODS: The expression levels of
      miR-126 and Crk protein in 338 GC patients were analyzed by quantitative real
      time polymerase chain reaction and immunohistochemistry, respectively. The
      relationship of miR-126 and Crk protein expression with clinicopathologic
      characteristics and clinical outcome was evaluated. RESULTS: Compared with
      matched adjacent non-tumor tissues, miR-126 was significantly down-regulated
      while Crk protein was significantly up-regulated in tumor tissues. A reduced miR
      126 expression and an elevated Crk protein expression, alone or in combination,
      statistically correlated with aggressive clinicopathological characteristics,
      such as larger tumor size, deeper local invasion, more lymph node metastasis,
      advanced TNM stage, and poorer prognosis. Multivariate analysis showed that
      combined miR-126-low/Crk protein-high expression was an independent unfavorable
      prognostic factor of GC. CONCLUSIONS: These results indicate for the first time
      that miR-126 down-regulation and Crk protein up-regulation may be synergistically
      associated with tumor progression in GC and may predict unfavorable prognosis of
      GC.

PMID- 29171988
TI  - High expression of NDRG3 associates with unfavorable overall survival in non
      small cell lung cancer.
AB  - BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the
      important members of the NDRG family which crucially take part in cell
      proliferation, differentiation and other biological processes. METHODS: In this
      present study, western-blotting analysis was performed to evaluate NDRG3
      expression in NSCLC cell lines. One-step quantitative reverse transcription
      polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and
      immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore
      the relationship between NDRG3 expression and the clinicopathological
      characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically
      higher in NSCLC cell lines and tissue samples, compared with that of in non
      cancerous cell line and tissue samples (p< 0.05). The IHC data demonstrated that
      the NDRG3 expression was significantly correlated with pathological grade (p=
      0.038), N (p= 0.020) and TNM stage (p= 0.002). Survival analysis and Kaplan-Meier
      curve indicated that NDRG3 expression (p= 0.002) and T (p= 0.047) were
      independently associated with the unfavorable overall survival of patients with
      NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a
      new predictor in NSCLC prognosis.

PMID- 29171989
TI  - Comparative analysis of immune function, hemorheological alterations and
      prognosis in colorectal cancer patients with different traditional Chinese
      medicine syndromes.
AB  - OBJECTIVE: The present study investigates the differences in immune function,
      hemorheological alterations and prognostic evaluation in colorectal cancer (CRC)
      patients with different traditional Chinese medicine (TCM) syndromes. METHODS: A
      total of 128 patients, diagnosed as stage II and III of CRC, were recruited. They
      were assigned into three TCM syndromes: deficiency syndrome, excess syndrome, and
      syndrome of intermingled deficiency and excess, and another 53 healthy
      individuals were selected as the control. Flow cytometry was used to determine
      the peripheral blood lymphocyte subsets (the levels of CD+3, CD+4, CD+8, NK
      cells, and the ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2). Whole blood viscosity
      (WBV), plasma viscosity (PV), hematocrit (Hct), erythrocyte sedimentation rate
      (ESR), plasma fibrinogen concentration (PFC) were measured using a fully
      automatic blood rheological instrument. The univariate analysis and Cox
      regression analysis were conducted to evaluate the prognosis of CRC patients with
      different TCM syndromes. RESULTS: Compared with healthy individuals, CRC patients
      with three different syndromes had lower levels of CD+3, CD+4, NK cells, and
      ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2, but higher level of CD+8, WBV, PV, Hct,
      ESR and PFC. Besides, patients with excess syndrome showed the highest levels of
      CD3+, CD4+ and NK cells, and ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2, but the
      lowest level of CD+8 among three syndromes, and those with deficiency syndrome
      showed an opposite trend. Compared with patients with excess syndrome, those with
      deficiency syndrome showed decreased WBV, PV, Hct, ESR and PFC. The pathological
      type, surgical approach, tumor node metastasis (TNM) stage, liver metastasis, TCM
      treatment time and different TCM syndromes were independent factors of prognostic
      survival in CRC patients except perioperative blood transfusion volume.
      CONCLUSIONS: Taken together, we conclude that patients with TCM deficiency
      syndrome has lower immune function and poorer prognosis while patients with TCM
      excess syndrome has higher immune function and better prognosis of CRC.

PMID- 29171990
TI  - Development of nanoparticle adjuvants to potentiate the immune response against
      diphtheria toxoid.
AB  - BACKGROUND: Over the years, diphtheria was known as contagious fatal infection
      caused by Corynebacterium diphtheria that affects upper respiratory system. The
      spread of diphtheria epidemic disease is best prevented by vaccination with
      diphtheria toxoid vaccine. Aluminum adjuvants were reported to stimulate the
      immune responses to killed and subunit vaccines. OBJECTIVE: Our study aimed to
      minimize adjuvant particles size, to gain insight of resulting immunity titer and
      impact on immune response antibody subtypes. METHODS: Aluminum salts and calcium
      phosphate adjuvants were prepared, followed by micro/nanoparticle adjuvants
      preparation. After formulation of diphtheria vaccine from diphtheria toxoid and
      developed adjuvants, we evaluated efficacy of these prepared vaccines based on
      their impact on immune response via measuring antibodies titer, antibodies
      isotyping and cytokines profile in immunized mice. RESULTS: A noteworthy increase
      in immunological parameters was observed; antibodies titer was higher in serum of
      mice injected with nanoparticle adjuvants-containing vaccine than mice injected
      with standard adjuvant-containing vaccine and commercial vaccine. Aluminum
      compounds adjuvants (nanoparticles and microparticles formulation) and
      microparticles calcium phosphate adjuvant induce TH2 response, while
      nanoparticles calcium phosphate and microparticles aluminum compounds adjuvants
      stimulate TH1 response. CONCLUSIONS: Different treatments to our adjuvant
      preparations (nanoparticles and microparticles formulation) had a considerable
      impact on vaccine immunogenicity.

PMID- 29171991
TI  - Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer's Disease
      Pathology Between Three Independent Assay Platforms.
AB  - BACKGROUND: To enhance the accuracy of clinical diagnosis for Alzheimer's disease
      (AD), pre-mortem biomarkers have become increasingly important for diagnosis and
      for participant recruitment in disease-specific treatment trials. Cerebrospinal
      fluid (CSF) biomarkers provide a low-cost alternative to positron emission
      tomography (PET) imaging for in vivo quantification of different AD pathological
      hallmarks in the brains of affected subjects; however, consensus around the best
      platform, most informative biomarker and correlations across different
      methodologies are controversial. OBJECTIVE: Assessing levels of Abeta-amyloid and
      tau species determined using three different versions of immunoassays, the
      current study explored the ability of CSF biomarkers to predict PET Abeta-amyloid
      (32 Abeta-amyloid-and 45 Abeta-amyloid+), as well as concordance between CSF
      biomarker levels and PET Abeta-amyloid imaging. METHODS: Prediction and
      concordance analyses were performed using a sub-cohort of 77 individuals (48
      healthy controls, 15 with mild cognitive impairment, and 14 with AD) from the
      Australian Imaging Biomarker and Lifestyle study of aging. RESULTS: Across all
      three platforms, the T-tau/Abeta42 ratio biomarker had modestly higher
      correlation with SUVR/BeCKeT (rho= 0.69-0.8) as compared with Abeta42 alone (rho=
      0.66-0.75). Differences in CSF biomarker levels between the PET Abeta-amyloid-and
      Abeta-amyloid+ groups were strongest for the Abeta42/Abeta40 and T-tau/Abeta42
      ratios (p < 0.0001); however, comparison of predictive models for PET Abeta
      amyloid showed no difference between Abeta42 alone and the T-tau/Abeta42 ratio.
      CONCLUSION: This study confirms strong concordance between CSF biomarkers and PET
      Abeta-amyloid status is independent of immunoassay platform, supporting their
      utility as biomarkers in clinical practice for the diagnosis of AD and for
      participant enrichment in clinical trials.

PMID- 29171992
TI  - Delirium Severity Post-Surgery and its Relationship with Long-Term Cognitive
      Decline in a Cohort of Patients without Dementia.
AB  - BACKGROUND: Delirium has been associated with more rapid cognitive decline.
      However, it is unknown whether increased delirium severity is associated with a
      higher rate of long-term cognitive decline. OBJECTIVE: To evaluate delirium
      severity and the presence and rate of cognitive decline over 36 months following
      surgery. METHODS: We examined patients from the Successful Aging after Elective
      Surgery Study, who were age >=70 years undergoing major elective surgery (N =
      560). Delirium severity was determined by the peak Confusion Assessment Method
      Severity (CAM-S) score for each patient's hospitalization and grouped based on
      the sample distribution: scores of 0-2, 3-7, and 8-19. A neuropsychological
      composite, General Cognitive Performance (GCP), and proxy-reported Informant
      Questionnaire for Cognitive Decline (IQCODE) were used to examine cognitive
      outcomes following surgery at 0, 1, and 2 months, and then every 6 months for up
      to 3 years. RESULTS: No significant cognitive decline was observed for patients
      with peak CAM-S scores 0-2 (-0.17 GCP units/year, 95% confidence interval [CI] 
      0.35, 0.01). GCP scores decreased significantly in the group with peak CAM-S
      scores 3-7 (-0.30 GCP units/year, 95% CI -0.51, -0.09), and decreased almost
      three times faster in the highest delirium severity group (peak CAM-S scores 8
      19; -0.82 GCP units/year, 95% CI -1.28, -0.37). A similar association was found
      for delirium severity and the proportion of patients who developed IQCODE
      impairment over time. CONCLUSION: Patients with the highest delirium severity
      experienced the greatest rate of cognitive decline, which exceeds the rate
      previously observed for patients with dementia, on serial neuropsychological
      testing administered over 3 years, with a dose-response relationship between
      delirium severity and long-term cognitive decline.

PMID- 29171993
TI  - Prevalence of Delirium in a Population of Elderly Outpatients with Dementia: A
      Retrospective Study.
AB  - BACKGROUND: Delirium is a multifactorial geriatric syndrome and often occurs in
      patients with cognitive impairment. It also remains under-recognized,
      specifically in elderly outpatients, because signs of delirium might overlap with
      symptoms of dementia. OBJECTIVE: The aim of the present study is to
      retrospectively apply the chart-based delirium instrument on a cohort of elderly
      outpatients with dementia, to assess prevalence and features of delirium in this
      population. METHODS: We randomly selected 650 medical records of outpatients
      referred to the "Neurogenetic Regional Centre" (CRN) of Lamezia Terme. Each
      evaluation included demographics, medical history, drugs, type and severity of
      dementia, and cognitive and functional status. Delirium was identified by the
      application of the chart-based delirium instrument. RESULTS: The prevalence of
      delirium was 13.3%. The study population was divided, according to the presence
      of delirium, into two subgroups. Compared to the no delirium group, the delirium
      group was significantly older and had greater cognitive impairment with lower
      MMSE scores both at baseline and at the end of the follow up. They also had a
      significant lower score on the ADL and IADL. In this group, a higher intake of
      antihypertensive and antipsychotic drugs, together with a lower intake of
      cholinesterase inhibitors and memantine, was observed. CONCLUSIONS: In this
      study, the chart-based delirium instrument was applied to an outpatient
      population affected by dementia and followed for a long time. Our data confirm
      the importance that age and frailty play on the genesis of delirium and suggest
      attention should be paid to the pharmacological treatment of these patients.

PMID- 29171995
TI  - High Caregiver Burden in Young Onset Dementia: What Factors Need Attention?
AB  - BACKGROUND: There is an increase in prevalence of young onset dementia (YOD). The
      specific problems among YOD patients and levels of caregiver burden (CB) in this
      group warrants further evaluation. OBJECTIVE: To evaluate and compare level of CB
      in YOD and late onset dementia (LOD). Also, we sought to understand the specific
      factors, such as neuropsychiatric symptoms, that may affect the levels of
      caregiver burden in the YOD group. METHODS: Patient-caregiver dyads with YOD and
      LOD were recruited from a tertiary neurology center. Levels of CB between YOD and
      LOD were compared among 183 patient-caregiver dyads. CB was quantified using the
      Zarit Burden Inventory (ZBI). Neuropsychological evaluations as well as the
      Neuropsychiatric Inventory were performed. Factors that influenced level of CB in
      YOD group was investigated with regression analyses. RESULTS: There were 57 YOD
      and 126 LOD dyads. Caregivers of YOD subjects reported significantly higher
      levels of burden compared to caregivers of LOD subjects (ZBI: 17.3 versus 13.94;
      p = 0.015). 52.6% of YOD caregivers reported a high caregiver burden. When
      compared to caregivers of LOD, the odds of a caregiver of YOD reporting high
      caregiver burden was 2.34 (95% CI: 1.22-4.49: p = 0.010). YOD dyads with a high
      caregiver burden had significantly higher neuropsychiatric inventory scores. Risk
      factors for high caregiver burden in YOD included family history of dementia and
      behavioral symptoms including disinhibited behavior, delusions, and apathy.
      CONCLUSION: Targeted support for caregivers of patients with YOD is needed to
      address the higher CB in this group.

PMID- 29171994
TI  - Hippocampal Stratum Radiatum, Lacunosum, and Moleculare Sparing in Mild Cognitive
      Impairment.
AB  - BACKGROUND: Alzheimer's disease (AD) is associated with atrophy in entorhinal
      cortex (ERC), the hippocampus, and its subfields Cornu Ammonis 1 (CA1) and
      subiculum, which predict conversion from mild cognitive impairment (MCI) to
      clinical AD. The stratum radiatum, lacunosum, and moleculare (SRLM) are also
      important gateways involving ERC and CA1, which are affected by early AD
      pathology. OBJECTIVE: To assess whether the SRLM is affected in MCI and AD.
      METHODS: In this proof-of-concept study, 27 controls, 13 subjects with AD, and 22
      with MCI underwent 3T MRI. T1 maps were used for whole-hippocampal volumetry, T2
      maps were segmented for hippocampal subfield areas, entorhinal cortex and
      subiculum thickness, and evaluated for SRLM integrity. RESULTS: Significant CA1
      atrophy and subiculum thinning were found in both AD and MCI compared to
      similarly aged controls. However, SRLM integrity was only significantly reduced
      in AD but not in MCI compared to controls. There were no significant differences
      in other hippocampal subfields (CA2, CA3/dentate gyrus) or ERC thickness between
      the groups. Finally, CA1 and CA3/DG areas and SRLM clarity were correlated with
      clinical and cognitive measurements of disease severity. CONCLUSION: Although
      this study was cross sectional, it suggests a progression of specific subfield
      changes from MCI to established AD that is associated with the reduced integrity
      of SRLM, which may reflect more widespread hippocampal involvement as the disease
      progresses and the relative preservation of SRLM in MCI. These results provide
      new MRI biomarkers for disease staging and understanding of the neurobiology in
      AD.

PMID- 29171996
TI  - Cerebrospinal Fluid C-C Motif Chemokine Ligand 2 Correlates with Brain Atrophy
      and Cognitive Impairment in Alzheimer's Disease.
AB  - BACKGROUND: Chronic neuroinflammation has been implicated in Alzheimer's disease
      (AD) pathology. OBJECTIVE: To investigate the association between cytokine and
      anti-amyloid-beta (Abeta) autoantibody levels and the degree of brain atrophy and
      cognitive impairment in AD patients. METHODS: Cerebrospinal fluid (CSF) levels of
      C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 8, C-X-C motif
      chemokine ligand 10, interleukin 6, and anti-Abeta autoantibody were evaluated in
      69 AD patients. Serum levels of CCL2 and anti-Abeta autoantibody were also
      examined. The degree of brain atrophy was assessed using the voxel-based specific
      regional analysis system for AD, which targets the volumes of interest (VOI) in
      medial temporal structures. Cognitive function was evaluated by
      neuropsychological testing, including the Mini-Mental State Examination (MMSE)
      and Frontal Assessment Battery (FAB). RESULTS: CSF CCL2 levels correlated
      significantly with the severity (p = 0.023) and the extent (p = 0.022) of VOI
      atrophy, and with the extent of gray matter atrophy (p = 0.039) in AD patients.
      CSF anti-Abeta autoantibody levels were inversely correlated with the severity of
      VOI atrophy (p = 0.020), the extent of VOI atrophy (p = 0.015), and the ratio of
      VOI/GM atrophy (r = -0.358, p = 0.004). CSF CCL2 levels were also inversely
      correlated with MMSE (p = 0.0497) and FAB scores (p = 0.016). CONCLUSIONS: CSF
      CCL2 levels are associated with the degree of medial temporal lobe and gray
      matter atrophy, and cognitive decline in AD.

PMID- 29171997
TI  - Tau and Amyloid Positron Emission Tomography Imaging Predict Driving Performance
      Among Older Adults with and without Preclinical Alzheimer's Disease.
AB  - Abnormal levels of Alzheimer's disease (AD) biomarkers, measured by positron
      emission tomography imaging using amyloid-based radiotracers and cerebrospinal
      fluid, are associated with impaired driving performance in older adults. We
      examined whether preclinical AD staging, defined using amyloid imaging and tau
      imaging using the radiotracer T807 (AKA flortaucipir or AV-1451), was associated
      with receiving a marginal/fail rating on a standardized road test (n = 42).
      Participants at Stage 2 (positive amyloid and tau scans) of preclinical AD were
      more likely to receive a marginal/fail rating compared to participants at Stage 0
      or 1. Stage 2 preclinical AD may manifest in worse driving performance.

PMID- 29171999
TI  - ABC Transporters Are Key Players in Alzheimer's Disease.
AB  - Human ATP-binding cassette (ABC) transporters mediate a critical function in the
      cell, namely the transport of molecules across lipid membranes. Associated to
      their ubiquitous tissue distribution, they are key players in cellular
      homeostasis but also potential causative or contributing factors for many
      pathologies, including Alzheimer's disease (AD). In the central nervous system
      (CNS), numerous ABC transporters are present throughout the brain parenchyma and
      especially at the blood-brain barrier (BBB). AD is a neurodegenerative disorder
      mainly characterized by extracellular deposition of amyloid-beta (Abeta) peptides
      and intracellular accumulation of hyperphosphorylated forms of tau protein.
      Besides being degraded via proteolytic and phagocytic processes mediated by brain
      parenchymal cells, a major mechanism for eliminating cerebral Abeta is through
      its transport across the BBB into the peripheral blood. In fact, many AD cases
      are associated with impaired Abeta clearance. Consistently, several studies have
      recently uncovered important roles for ABC transporters in AD pathophysiology.
      Hence, this review focuses on the relevance of ABC transporters in CNS
      homeostasis by highlighting AD as a strong example of the deleterious
      consequences that might result from the former's altered expression and/or
      activity in the brain. The potentiality of human ABC transporters as novel
      pharmacological targets for both the diagnosis and therapeutics of AD is
      emphasized.

PMID- 29171998
TI  - Biological, Neuroimaging, and Neurophysiological Markers in Frontotemporal
      Dementia: Three Faces of the Same Coin.
AB  - Frontotemporal dementia (FTD) is a heterogeneous clinical, genetic, and
      neuropathological disorder. Clinical diagnosis and prediction of
      neuropathological substrates are hampered by heterogeneous pictures. Diagnostic
      markers are key in clinical trials to differentiate FTD from other
      neurodegenerative dementias. In the same view, identifying the neuropathological
      hallmarks of the disease is key in light of future disease-modifying treatments.
      The aim of the present review is to unravel the progress in biomarker discovery,
      discussing the potential applications of available biological, imaging, and
      neurophysiological markers.

PMID- 29172002
TI  - Mental States in Moving Shapes: Distinct Cortical and Subcortical Contributions
      to Theory of Mind Impairments in Dementia.
AB  - Impaired capacity for Theory of Mind (ToM) represents one of the hallmark
      features of the behavioral variant of frontotemporal dementia (bvFTD) and is
      suggested to underpin an array of socioemotional disturbances characteristic of
      this disorder. In contrast, while social processing typically remains intact in
      Alzheimer's disease (AD), the cognitive loading of socioemotional tasks may
      adversely impact mentalizing performance in AD. Here, we employed the Frith-Happe
      animations as a dynamic on-line assessment of mentalizing capacity with reduced
      incidental task demands in 18 bvFTD, 18 AD, and 25 age-matched Controls.
      Participants viewed silent animations in which geometric shapes interact in
      Random, Goal-Directed, and ToM conditions. An exclusive deficit in ToM
      classification was observed in bvFTD relative to Controls, while AD patients were
      impaired in the accurate classification of both Random and ToM trials.
      Correlation analyses revealed robust associations between ToM deficits and carer
      ratings of affective empathy disruption in bvFTD, and with episodic memory
      dysfunction in AD. Voxel-based morphometry analyses further identified
      dissociable neural correlates contingent on patient group. A distributed network
      of medial prefrontal, frontoinsular, striatal, lateral temporal, and parietal
      regions were implicated in the bvFTD group, whereas the right hippocampus
      correlated with task performance in AD. Notably, subregions of the cerebellum,
      including lobules I-IV and V, bilaterally were implicated in task performance
      irrespective of patient group. Our findings reveal new insights into the
      mechanisms potentially mediating ToM disruption in dementia syndromes, and
      suggest that the cerebellum may play a more prominent role in social cognition
      than previously appreciated.

PMID- 29172001
TI  - Co-Expression of Glia Maturation Factor and Apolipoprotein E4 in Alzheimer's
      Disease Brain.
AB  - Apolipoprotein E4 (ApoE4) is a major genetic risk factor for Alzheimer's disease
      (AD). The E4 allele of ApoE plays a crucial role in the inflammatory and
      neurodegenerative processes associated with AD. This is evident from the multiple
      effects of the ApoE isoforms in amyloid-beta (Abeta) aggregation. Glia maturation
      factor (GMF) is a brain-specific neuroinflammatory protein that we have
      previously demonstrated to be significantly upregulated in various regions of AD
      brains compared to non-AD control brains and that it induces neurodegeneration.
      We have previously reported that GMF is predominantly expressed in the reactive
      astrocytes surrounding amyloid plaques (APs) in AD brain. In the present study,
      using immunohistochemical and dual immunofluorescence staining, we show the
      expression and colocalization of GMF and ApoE4 in AD brains. Our results show
      that ApoE4 is present within the APs of AD brain. Further, we found that GMF and
      ApoE4 were strongly expressed and co-associated in APs and in the reactive
      astrocytes surrounding APs in AD. An increased expression of GMF in APs and
      neurofibrillary tangles in the AD brain, and the co-localization of GMF and ApoE4
      in APs suggest that GMF and ApoE4 together should be contributing to the
      neuropathological changes associated with AD.

PMID- 29172000
TI  - Translational Research in Alzheimer's and Prion Diseases.
AB  - Translational neuroscience integrates the knowledge derived by basic neuroscience
      with the development of new diagnostic and therapeutic tools that may be applied
      to clinical practice in neurological diseases. This information can be used to
      improve clinical trial designs and outcomes that will accelerate drug
      development, and to discover novel biomarkers which can be efficiently employed
      to early recognize neurological disorders and provide information regarding the
      effects of drugs on the underlying disease biology. Alzheimer's disease (AD) and
      prion disease are two classes of neurodegenerative disorders characterized by
      incomplete knowledge of the molecular mechanisms underlying their occurrence and
      the lack of valid biomarkers and effective treatments. For these reasons, the
      design of therapies that prevent or delay the onset, slow the progression, or
      improve the symptoms associated to these disorders is urgently needed. During the
      last few decades, translational research provided a framework for advancing
      development of new diagnostic devices and promising disease-modifying therapies
      for patients with prion encephalopathies and AD. In this review, we provide
      present evidence of how supportive can be the translational approach to the study
      of dementias and show some results of our preclinical studies which have been
      translated to the clinical application following the 'bed-to-bench-and-back'
      research model.

PMID- 29172003
TI  - Functional brain dynamic analysis of ADHD and control children using nonlinear
      dynamical features of EEG signals.
AB  - Attention deficit hyperactivity disorder is a neurodevelopmental condition
      associated with varying levels of hyperactivity, inattention, and impulsivity.
      This study investigates brain function in children with attention deficit
      hyperactivity disorder using measures of nonlinear dynamics in EEG signals during
      rest. During eyes-closed resting, 19 channel EEG signals were recorded from 12
      ADHD and 12 normal age-matched children. We used the multifractal singularity
      spectrum, the largest Lyapunov exponent, and approximate entropy to quantify the
      chaotic nonlinear dynamics of these EEG signals. As confirmed by Wilcoxon rank
      sum test, largest Lyapunov exponent over left frontal-central cortex exhibited a
      significant difference between ADHD and the age-matched control groups. Further,
      mean approximate entropy was significantly lower in ADHD subjects in prefrontal
      cortex. The singularity spectrum was also considerably altered in ADHD compared
      to control children. Evaluation of these features was performed by two
      classifiers: a Support Vector Machine and a Radial Basis Function Neural Network.
      For better comparison, subject classification based on frequency band power was
      assessed using the same types of classifiers. Nonlinear features provided better
      discrimination between ADHD and control than band power features. Under four-fold
      cross validation testing, support vector machine gave 83.33% accurate
      classification results.

PMID- 29172004
TI  - Early-Onset Myopathies: Clinical Findings, Prevalence of Subgroups and Diagnostic
      Approach in a Single Neuromuscular Referral Center in Germany.
AB  - BACKGROUND: Early-onset myopathies are a heterogeneous group of neuromuscular
      diseases with broad clinical, genetic and histopathological overlap. The
      diagnostic approach has considerably changed since high throughput genetic
      methods (next generation sequencing, NGS) became available. OBJECTIVE: We present
      diagnostic subgroups in a single neuromuscular referral center and describe an
      algorithm for the diagnostic work-up. METHODS: The diagnostic approach of 98
      index patients was retrospectively analysed. In 56 cases targeted sequencing of a
      known gene was performed, in 44 patients NGS was performed using large muscle
      specific panels, and in 12 individuals whole exome sequencing (WES) was
      undertaken. One patient was diagnosed via array CGH. Clinical features of all
      patients are provided. RESULTS: The final diagnosis could be found in 63 out of
      98 patients (64%) with molecular genetic analysis. In 55% targeted gene
      sequencing could establish the genetic diagnosis. However, this rate largely
      depended on the presence of distinct histological or clinical features. NGS
      (large myopathy-related panels and WES) revealed genetic diagnosis in 58.5% (52%
      and 67%, respectively). The genes detected by WES in our cohort of patients were
      all covered by the panels. Based on our findings we propose an algorithm for a
      practical diagnostic approach.Prevalences:MTM1- and LAMA2-patients are the two
      biggest subgroups, followed by SEPN1-, RYR1- and Collagen VI-related diseases.
      31% of genetically confirmed cases represents a group with overlap between
      "congenital myopathies (CM)" and "congenital muscular dystrophies (CMD)". In 36%
      of the patients a specific genetic diagnosis could not be assigned. CONCLUSIONS:
      A final diagnosis can be confirmed by high throughput genetic analysis in 58.5%
      of the cases, which is a higher rate than reported in the literature for muscle
      biopsy and should in many cases be considered as a first diagnostic tool. NGS
      cannot replace neuromuscular expertise and a close discussion with the
      geneticists on NGS is mandatory. Targeted candidate gene sequencing still plays a
      role in selected cases with highly suspicious clinical or histological features.
      There is a relevant clinical and genetic overlap between the entities CM and CMD.

PMID- 29172005
TI  - Cytokine Profiling of Serum Allows Monitoring of Disease Progression in Inclusion
      Body Myositis.
AB  - BACKGROUND: Inclusion body myositis is a late onset inflammatory myopathy lacking
      reliable serum biomarkers for diagnosis and for disease progression. OBJECTIVE:
      To identify diagnostic and predictive biomarkers, cytokine profiling is used to
      assess the potential of cytokines to discriminate between cases and controls and
      to assess whether treatment with methotrexate can influence biomarkers associated
      with disease progression. METHODS: The diagnostic and follow-up potential of 48
      cytokines was tested using Bioplex-assay and ELISA in sera of healthy
      individuals, IBM patients and patients with other neuromuscular disorders.
      RESULTS: Ten cytokines (TRAIL, IL-8, MIF, MCP-1, LIF, IP-10, IFN-alpha2, MIG,
      bNGF and IL-3) were identified to be good to excellent markers to discern IBM
      patients from healthy controls. Three cytokines (IP-10, Eotaxin and SDF1A)
      changed significantly upon methotrexate treatment as compared with the natural
      clinical course. Muscle strength loss was associated with changes in IL-8 and
      SDF1A levels. IFN-gamma levels were only associated with survival of IBM patients
      before correction for multiple comparisons. DISCUSSION: Cytokine profiling can
      discriminate IBM patients from healthy controls and other neuromuscular
      disorders. Immunosuppression with methotrexate affects cytokine levels in IBM. IL
      8 and SDF1A could serve as biomarkers for disease progression.

PMID- 29172006
TI  - Two Cases of Spinal Muscular Atrophy Type II with Eosinophilic Oesophagitis.
AB  - Although primarily characterised by loss of motor neurons from the anterior horn
      of spinal cord and muscle atrophy, spinal muscular atrophy (SMA) is now
      recognised as a multi-systemic disorder. Here, we report two SMA Type II patients
      with eosinophilic oesophagitis (EoE), a rare, chronic immune/antigen-mediated
      condition. One patient presented with dysphagia and poor weight gain, and the
      second patient had symptoms of gastro-oesophageal reflux (GOR) and poor weight
      gain. In both patients, macroscopic observations during gastroscopy indicated
      typical signs of EoE, which were verified during histological examination of
      oesophageal biopsies. Given that there is a specific treatment strategy for EoE,
      these cases highlight the importance of considering this condition in clinical
      investigations - especially for patients with SMA - who have GOR, discomfort, and
      oral aversion.

PMID- 29172007
TI  - Frequency-specific effects of repetitive magnetic stimulation on primary
      astrocyte cultures.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive
      technique that uses magnetic pulses over the cranium to induce electrical
      currents in underlying cortical tissue. Although rTMS has shown clinical utility
      for a number of neurological conditions, we have only limited understanding of
      how rTMS influences cellular function and cell-cell interactions. OBJECTIVE: In
      this study, we sought to investigate whether repeated magnetic stimulation (rMS)
      can influence astrocyte biology in vitro. METHOD: We tested four different rMS
      frequencies and measured the calcium response in primary neonatal astrocyte
      cultures. We also tested the effect of rMS on astrocyte migration and
      proliferation in vitro. We tested 3 to 4 culture replicates and 17 to 34 cells
      for each rMS frequency (sham, 1 Hz, cTBS, 10 Hz and biomemetic high frequency
      stimulation - BHFS). RESULTS: Of all frequencies tested, 1 Hz stimulation
      resulted in a statistically significant rise in intracellular calcium in the
      cytoplasmic and nuclear compartments of the cultured astrocytes. This calcium
      rise did not affect migration or proliferation in the scratch assay, though
      astrocyte hypertrophy was reduced in response to 1 Hz rMS, 24 hours post scratch
      injury. CONCLUSION: Our results provide preliminary evidence that rMS can
      influence astrocyte physiology, indicating the potential for a novel mechanism by
      which rTMS can influence brain activity.

PMID- 29172008
TI  - Effects of cerebrolysin on nerve growth factor system in the aging rat brain.
AB  - BACKGROUND: Aging is associated with some cognitive decline and enhanced risk of
      development of neurodegenerative diseases. It is assumed that altered metabolism
      and functions of neurotrophin systems may underlie these age-related functional
      and structural modifications. CerebrolysinTM (CBL) is a neuropeptide mixture with
      neurotrophic effects, which is widely used for the treatment of stroke and
      traumatic brain injury patients. It is also evident that CBL has an overall
      beneficial effect and a favorable benefit-risk ratio in patients with dementia.
      However, the effects of CBL on cognition and brain neurotrophin system in normal
      aging remain obscure. OBJECTIVE: The aim of the present study was to examine the
      age-related modifications of endogenous neurotrophin systems in the brain of male
      Wistar rats and the effects of CBL on learning and memory as well as the levels
      neurotrophins and their receptors. METHODS: Old (23-24 months) and young (2-3
      months) male Wistar rats were used for the study. A half of animals were
      subjected to CBL course (2.5 ml/kg, 20 i.p. injections). Behavior of rats was
      studied using the open field test and simple water maze training. The contents of
      NGF and BDNF were studied using enzyme-linked immunosorbent assay; the expression
      of neurotrophin receptors was estimated by Western-blot analysis. RESULTS: CBL
      treatment did not affect general status, age-related weight changes, general
      locomotor activity as well as general brain histology. In a water maze task, a
      minor effect of CBL was observed in old rats at the start of training and no
      effect on memory retention was found. Aging induced a decrease in neurotrophin
      receptors TrkA, TrkB, and p75NTR in the neocortex. CBL counteracted effects of
      aging on neocortical TrkA and p75NTR receptors and decreased expression of proNGF
      without influencing overall NGF levels. BDNF system was not significantly
      affected by CBL. CONCLUSION: The pro-neuroplastic "antiaging" effects of CBL in
      the neocortex of old animals were generally related to the NGF rather than the
      BDNF system.

PMID- 29172011
TI  - Therapy and rehabilitation of mild brain injury/concussion: Systematic review.
AB  - BACKGROUND: Assessment of therapies for the key consequences of mild traumatic
      brain injury (mTBI)/concussion is required. OBJECTIVE: Identify all RCTs of
      mTBI/concussion therapy, risks of bias, and therapies with significant positive
      results. METHODS: 17 electronic, 9 grey-literature databases searched without
      language/date restrictions; independent assessment of 1450 Abstracts/titles, 141
      fulltext articles, 14 included RCTs. RESULTS: Four RCTs used American Congress of
      Rehabilitation TBI definition, others used unique definitions. Risk of bias: 43%
      low risk randomization; 14% concealed assignments; 21% blinded
      participants/personnel; 57% blinded assessors; 64% low risk attrition; 100% no
      selective reporting. Eleven RCTs included only mTBI. Ten significant positive
      results: six cognitive behavioral therapy (CBT), three videotape, pagers or
      personal digital assistants, and one physical therapy. One of referrals to health
      professionals no significant positive results. Three RCTs included both mTBI and
      moderate TBI. We wished to assess if authors proved using same interventions with
      both groups is appropriate. Two used CBT, one used pagers. All three RCTs
      significant positive results but results for their mild and moderate TBI patients
      were not separated. Two RCTs assessed return to work and no differences between
      intervention. CONCLUSION: Of 14 RCTs, six CBT, four digital assistants or
      videotape feedback and one physical therapy all had significant positive results.
      One referred patients to consultants and no significant positive results. Two
      assessed return to employment and no differences between interventions.
      Limitations are: (1) only four RCTs used the same concussion definition; (2)
      average age 38 (except for one study of adolescents, (3) all studies used unique
      interventions; (4) most authors used multiple interventions and effects could not
      be separated; (5) substantial attrition from eligibles to randomization, (4) only
      64% at low risk from randomization, (5) 80 different outcome measures and meta
      analysis was not possible, (6) only two studies assessed return to work.

PMID- 29172009
TI  - EPO-releasing neural precursor cells promote axonal regeneration and recovery of
      function in spinal cord traumatic injury.
AB  - BACKGROUND: Spinal cord injury (SCI) is a debilitating condition characterized by
      a complex of neurological dysfunctions ranging from loss of sensation to partial
      or complete limb paralysis. Recently, we reported that intravenous administration
      of neural precursors physiologically releasing erythropoietin (namely Er-NPCs)
      enhances functional recovery in animals following contusive spinal cord injury
      through the counteraction of secondary degeneration. Er-NPCs reached and
      accumulated at the lesion edges, where they survived throughout the prolonged
      period of observation and differentiated mostly into cholinergic neuron-like
      cells. OBJECTIVE: The aim of this study was to investigate the potential
      reparative and regenerative properties of Er-NPCs in a mouse experimental model
      of traumatic spinal cord injury. METHODS AND RESULTS: We report that Er-NPCs
      favoured the preservation of axonal myelin and strongly promoted the regrowth
      across the lesion site of monoaminergic and chatecolaminergic fibers that reached
      the distal portions of the injured cord. The use of an anterograde tracer
      transported by the regenerating axons allowed us to assess the extent of such a
      process. We show that axonal fluoro-ruby labelling was practically absent in
      saline-treated mice, while it resulted very significant in Er-NPCs transplanted
      animals. CONCLUSION: Our study shows that Er-NPCs promoted recovery of function
      after spinal cord injury, and that this is accompanied by preservation of
      myelination and strong re-innervation of the distal cord. Thus, regenerated axons
      may have contributed to the enhanced recovery of function after SCI.

PMID- 29172010
TI  - Extended Multiple-Field High-Definition transcranial direct current stimulation
      (HD-tDCS) is well tolerated and safe in healthy adults.
AB  - BACKGROUND: High definition transcranial direct current stimulation (HD-tDCS) has
      been administered over single brain regions for small numbers of sessions.
      Safety, feasibility and tolerability of HD-tDCS over multiple brain regions,
      multiple daily stimulations and long periods are not established. OBJECTIVE: We
      studied safety, feasibility and tolerability of daily HD-tDCS over 2-4 brain
      regions for 20 sessions in healthy adults. METHODS: Five healthy adults underwent
      physical and neurological examination, electrocardiogram (EKG),
      electroencephalogram (EEG) and cognitive screening (ImpACT) before, during and
      after HD-tDCS. Four networks (left/right temporoparietal and frontal) were
      stimulated in sequence (20 min each) using HD-tDCS in 20 daily sessions. Sessions
      1-10 included sequential stimulation of both temporoparietal networks, sessions
      11-15 stimulations of 4 networks and sessions 16-20 two daily stimulation cycles
      of 4 networks/cycle (1.5 mA/network). Side effects, ImpACT scores and EEG power
      spectrum were compared before and after HD-tDCS. RESULTS: All subjects completed
      the trial. Adverse events were tingling, transient redness at the stimulation
      site, perception of continuing stimulation after end of session and one self
      resolving headache. EEG power spectrum showed decreased delta power in frontal
      areas several days after HD-tDCS. While at the group level ImpACT scores did not
      differ before and after stimulations, we found a trend for correlation between
      decreased EEG delta power and individual improvements in ImpACT scores after HD
      tDCS. CONCLUSION: Prolonged, repeat daily stimulation of multiple brain regions
      using HD-tDCS is feasible and safe in healthy adults. Preliminary EEG results
      suggest that HD-tDCS may induce long lasting changes in excitability in the
      brain.

PMID- 29172012
TI  - Do whole body vibration exercises affect lower limbs neuromuscular activity in
      populations with a medical condition? A systematic review.
AB  - BACKGROUND: The use of surface electromyography (sEMG) to evaluate muscle
      activation when executing whole body vibration exercises (WBVE) in studies
      provide neuromuscular findings, in healthy and diseased populations. OBJECTIVES:
      Perform a systematic review of the effects of WBVE by sEMG of lower limbs in non
      healthy populations. METHODS: The search using the defined keywords was performed
      in PubMed, PEDRo and EMBASE databases by three independent researchers. Applying
      the PRISMA statement several studies were selected according to eligibility
      criteria and organized for the review. Full papers were included if they
      described effects of WBVE for the treatment of illnesses, evaluated by sEMG of
      lower limbs independently on the year of the publication; in comparison or
      associated with other treatment and evaluation techniques. RESULTS: Seven
      publications were selected; two in spinal cord injury patients, one in
      Friedreich's ataxia patients, three in stroke patients and one study in breast
      cancer survivors. Reported effects of WBV in were muscle activation by sEMG and
      also on strength, blood flow and exercise resistance; even in paretic limbs.
      CONCLUSION: By the use of sEMG it was verified that WBVE elicits muscle
      activation in diseased population. These results may lead to the definition of
      exercise protocols to maintain or increase muscular activation. However, due to
      the heterogeneity of methods among studies, there is currently no consensus on
      the sEMG signal processing. These strategies might also induce effects on muscle
      strength, balance and flexibility in these and other illnesses.

PMID- 29172015
TI  - Tibial impingement secondary to distal fibular lag screw placement: A case
      report.
AB  - Impingement, tibial erosions, and "painful hardware" caused by a lag screw used
      for malleolar fracture stabilization are rare occurrences. We report a case of a
      symptomatic lag screw, used to fix a distal fibular fracture, that impinged on
      the distal tibial and causing symptoms. Awareness of the condition and early
      diagnosis based on thoughtful review of CT images are key to symptom alleviation.
      A review of the published data on the complication of "painful hardware"
      following ankle fracture fixation is also presented.

PMID- 29172013
TI  - The association between brain activity and motor imagery during motor illusion
      induction by vibratory stimulation.
AB  - BACKGROUND: The association between motor imagery ability and brain neural
      activity that leads to the manifestation of a motor illusion remains unclear.
      OBJECTIVE: In this study, we examined the association between the ability to
      generate motor imagery and brain neural activity leading to the induction of a
      motor illusion by vibratory stimulation. METHODS: The sample consisted of 20
      healthy individuals who did not have movement or sensory disorders. We measured
      the time between the starting and ending points of a motor illusion (the time to
      illusion induction, TII) and performed electroencephalography (EEG). We conducted
      a temporo-spatial analysis on brain activity leading to the induction of motor
      illusions using the EEG microstate segmentation method. Additionally, we assessed
      the ability to generate motor imagery using the Japanese version of the Movement
      Imagery Questionnaire-Revised (JMIQ-R) prior to performing the task and examined
      the associations among brain neural activity levels as identified by microstate
      segmentation method, TII, and the JMIQ-R scores. RESULTS: The results showed four
      typical microstates during TII and significantly higher neural activity in the
      ventrolateral prefrontal cortex, primary sensorimotor area, supplementary motor
      area (SMA), and inferior parietal lobule (IPL). Moreover, there were significant
      negative correlations between the neural activity of the primary motor cortex
      (MI), SMA, IPL, and TII, and a significant positive correlation between the
      neural activity of the SMA and the JMIQ-R scores. CONCLUSION: These findings
      suggest the possibility that a neural network primarily comprised of the neural
      activity of SMA and M1, which are involved in generating motor imagery, may be
      the neural basis for inducing motor illusions. This may aid in creating a new
      approach to neurorehabilitation that enables a more robust reorganization of the
      neural base for patients with brain dysfunction with a motor function disorder.

PMID- 29172016
TI  - Applicability of simplified computational models in prediction of peak wall
      stress in abdominal aortic aneurysms.
AB  - In the paper impact of different material models on the calculated peak wall
      stress (PWS) and peak wall rupture risk (PWRR) in abdominal aortic aneurysms
      (AAAs) is assessed. Computational finite element models of 70 patient-specific
      AAAs were created using two different material models - a realistic one based on
      mean population results of uniaxial tests of AAA wall considered as reference,
      and a 100 times stiffer artificial model. The calculated results of PWS and PWRR
      were tested to evaluate statistical significance of differences caused by the non
      realistic material model. It was shown that for majority of AAAs the differences
      are insignificant but for some 10% of them their relative differences exceed 20%
      which may lead to incorrect decisions on their surgical treatment. This
      percentage of failures favours application of realistic material models in
      clinical practise although they are much more time-consuming.

PMID- 29172018
TI  - Are vaginal estrogens effective for preventing urinary tract infection in
      postmenopausal women?
AB  - INTRODUCTION: Urinary tract infection commonly affects postmenopausal women,
      probably because of the changes in vaginal flora secondary to estrogen
      deficiency. So, the use of vaginal estrogens could revert this process and then
      decrease the risk of infection. However, it is not clear whether they are really
      effective. METHODS: To answer this question we used Epistemonikos, the largest
      database of systematic reviews in health, which is maintained by screening
      multiple information sources, including MEDLINE, EMBASE, Cochrane, among others.
      We extracted data from the systematic reviews, reanalyzed data of primary
      studies, conducted a meta-analysis and generated a summary of findings table
      using the GRADE approach. RESULTS AND CONCLUSIONS: We identified seven systematic
      reviews including four primary studies overall and all were randomized trials. We
      concluded it is not clear whether vaginal estrogens decrease the risk of
      symptomatic urinary infection because the certainty of the available evidence is
      very low.

PMID- 29172017
TI  - Scutellarin Prevents Nonalcoholic Fatty Liver Disease (NAFLD) and Hyperlipidemia
      via PI3K/AKT-Dependent Activation of Nuclear Factor (Erythroid-Derived 2)-Like 2
      (Nrf2) in Rats.
AB  - BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a condition characterized
      by excessive fat accumulation in the form of triglycerides. The incidence of
      NAFLD and hyperlipidemia, with their associated risks of end-stage liver and
      cardiovascular diseases, is increasing rapidly. This study aimed to investigate
      the effects of scutellarin on the experimental NAFLD in high-fat diet fed and
      chronic stress rats, and its possible mechanism. MATERIAL AND METHODS Sprague
      Dawley rats were fed with high-fat diet and subjected to chronic stress for 12
      weeks, and administered orally with scutellarin for 4 weeks (n=8), and then blood
      and livers were harvested for analyzing. Enzyme activity assay,
      immunofluorescence, Western blot, and quantitative RT-PCR were performed to
      analyze the factors of the oxidant/antioxidant system and pathway. RESULTS After
      the high-fat diet and chronic stress administration for 12 weeks, serum and liver
      lipid metabolism of treatment groups with the different doses of SCU effectively
      improved and the degree of oxidative damage reduced. Using Western blot assay and
      immunofluorescence (IF) staining assay, Nrf2, HO-1, and PI3K, and AKT proteins
      significantly increased after SCU treatment for 4 weeks (P<0.01). The hepatic
      mRNA expression of HO-1, NQO1, and Nrf2 in SCU treatment groups was upregulated
      significantly through quantitative RT-PCR assay (P<0.05). However, compared to
      the positive control group, no difference was detected in the SCU (100 or 300
      mg/kg) groups (P>0.05). These results indicate that SCU protects against NAFLD in
      rats via attenuation of oxidative stress. CONCLUSIONS The antioxidant effects of
      SCU on NAFLD are possibly dependent on PI3K/AKT activation with subsequent Nrf2
      nuclear translocation, which increases expression of HO-1 and NQO1. We therefore
      suggest that breviscapine may be a potentially useful therapeutic strategy for
      NAFLD and hyperlipidemia.

PMID- 29172019
TI  - The Long-Term Stability of KO2 in K-O2 Batteries.
AB  - The rechargeable K-O2 battery is recognized as a promising energy storage
      solution owing to its large energy density, low overpotential, and high coulombic
      efficiency based on the single-electron redox chemistry of potassium superoxide.
      However, the reactivity and long-term stability of potassium superoxide remains
      ambiguous in K-O2 batteries. Parasitic reactions are explored and the use of ion
      chromatography to quantify trace amounts of side products is demonstrated. Both
      quantitative titrations and differential electrochemical mass spectrometry
      confirm the highly reversible single-electron transfer process, with 98 %
      capacity attributed to the formation and decomposition of KO2 . In contrast to
      the Na-O2 counterparts, remarkable shelf-life is demonstrated for K-O2 batteries
      owing to the thermodynamic and kinetic stability of KO2 , which prevents the
      spontaneous disproportionation to peroxide. This work sheds light on the
      reversible electrochemical process of K+ +e- +O2 <->KO2 .

PMID- 29172020
TI  - Evaluation of the effect of different post materials and adhesive systems on the
      bonding strength of short-post technique for primary teeth.
AB  - BACKGROUND: The most important process in treating grossly decayed teeth,
      including decay in the pulp, is the ability to hold a retainer in for a short
      time. AIM: The aim of this study was to investigate the bond strengths of
      different adhesive systems and post materials on primary teeth. DESIGN: One
      hundred and twenty extracted maxillar primary central incisor teeth were randomly
      divided into two main groups (total-etch and self-etch adhesive systems) and five
      subgroups (1: control-nanohybrid composite resin, 2: pre-impregnated glass fiber,
      3: unsaturated glass fiber, 4: polyethylene fiber, 5: short-fiber reinforced
      composite resin). The push-out test was performed using a universal testing
      machine with a crosshead speed of 0.5 mm/min. RESULTS: No statistically
      significant difference was detected between the two different adhesive systems
      and five different materials in terms of the maximum values measured for
      fractures in the specimens when both the adhesive materials and the short-post
      materials were evaluated separately (P > 0.05). However, as a result of multiple
      comparisons made, it was found that statistical differences between the groups
      applying the total-etch adhesive system occurred in Groups 3 and 5. The highest
      push-out test values were measured in Group 5 and Group 1, and the lowest value
      in Group 3. Although the fracture type distribution in the total-etch adhesive
      system groups was not statistically different based on the material used (chi2  =
      11,865; P = 0.309), the self-etch adhesive systems did show differences (chi2  =
      28,463; P < 0.001). Both the total-etch and the self-etch adhesive system groups
      showed mostly adhesive failures. CONCLUSION: The fiber-reinforced and nanohybrid
      composite resin had higher values in the short-post technique, and there was no
      significant difference between the different fiber posts.

PMID- 29172021
TI  - Early-onset type 2 diabetes: Age gradient in clinical and behavioural risk
      factors in 5115 persons with newly diagnosed type 2 diabetes-Results from the DD2
      study.
AB  - AIM: To examine the association between early onset of type 2 diabetes mellitus
      (DM) and clinical and behavioural risk factors for later complications of
      diabetes. METHODS: We conducted a cross-sectional study of 5115 persons with
      incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic
      Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis
      among those diagnosed at <=45 years (early onset) with diagnosis age 46 to 55, 56
      to 65 (average onset = reference), 66 to 75, and >75 years (late onset).
      Prevalence ratios (PRs) were computed by using Poisson regression. RESULTS: Poor
      glucose control, ie, HbA1c >= 75 mmol/mol (>=9.0%) in the early-, average-, and
      late-onset groups was observed in 12%, 7%, and 1%, respectively (PR 1.70 [95%
      confidence intervals (CI) 1.27, 2.28] and PR 0.17 [95% CI 0.06, 0.45]). A similar
      age gradient was observed for severe obesity (body mass index > 40 kg/m2 : 19%
      vs. 8% vs. 2%; PR 2.41 [95% CI 1.83, 3.18] and 0.21 (95% CI 0.08, 0.57]),
      dyslipidemia (90% vs. 79% vs. 68%; PR 1.14 [95% CI 1.10, 1.19] and 0.86 [95% CI
      0.79, 0.93]), and low-grade inflammation (C-reactive protein > 3.0 mg/L: 53% vs.
      38% vs. 26%; PR 1.41 [95% CI 1.12, 1.78] and 0.68 [95% CI 0.42, 1.11]). Daily
      smoking was more frequent and meeting physical activity recommendations less
      likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age
      gradient, with increasing prevalence of clinical and behavioural risk factors the
      younger the onset age of type 2 DM. Younger persons with early-onset type 2 DM
      need clinical awareness and support.

PMID- 29172022
TI  - Structure-Activity Relationships for Pt-Free Metal Phosphide Hydrogen Evolution
      Electrocatalysts.
AB  - In the field of renewable energy, the splitting of water into hydrogen and oxygen
      fuel gases using water electrolysis is a prominent topic. Traditionally, these
      catalytic processes have been performed by platinum-group metal catalysts, which
      are effective at promoting water electrolysis but expensive and rare. The search
      for an inexpensive and Earth-abundant catalyst has led to the development of 3d
      transition-metal phosphides for the hydrogen evolution reaction. These catalysts
      have shown excellent activity and stability. In this review, we discuss the
      electronic and crystal structures of bulk and surface of selected Fe, Co, and Ni
      phosphides, and their relationships to the experimental catalytic activity. The
      various synthetic protocols towards the state-of-the-art transition metal
      phosphide electrocatalysts are also discussed.

PMID- 29172023
TI  - Investigations of the local distortions and EPR parameters for Cu2+ in xNa2 O-(30
      x)K2 O-70B2 O3 (5 <= x <= 25 mol%) glasses.
AB  - The local distortions and electron paramagnetic resonance parameters for Cu2+ in
      the mixed alkali borate glasses xNa2 O-(30-x)K2 O-70B2 O3 (5 <= x <= 25 mol%) are
      theoretically studied with distinct modifier Na2 O compositions x. Owing to the
      Jahn-Teller effect, the octahedral [CuO6 ]10- clusters show significant
      tetragonal elongation ratios p ~19% along the C4 axis. With the increase of
      composition x, the cubic field parameter Dq and the orbital reduction factor k
      exhibit linearly and quasi-linearly decreasing tendencies, respectively, whereas
      the relative tetragonal elongation ratio p has quasi-linearly increasing rule
      with some fluctuations, leading to the minima of g factors at x = 10 mol%. The
      composition dependences of the optical spectra and the electron paramagnetic
      resonance parameters are suitably reproduced by the linear or quasi-linear
      relationships of the relevant quantities (i.e., Dq, k, and p) with x. The above
      composition dependences are analyzed from mixed alkali effect, which brings
      forward the modifications of the local crystal-fields and the electronic cloud
      distribution around Cu2+ with the variation of the composition of Na2 O.

PMID- 29172024
TI  - Daptomycin excretion into human milk.

PMID- 29172025
TI  - Vitamin D ratio and glycaemic control in individuals with type 2 diabetes
      mellitus: A systematic review.
AB  - Several studies have suggested a favorable role for vitamin D in glycaemic
      metabolism and its potential as adjuvant treatment of type 2 diabetes mellitus.
      This review discusses the role of vitamin D in the glycaemic control of
      individuals with type 2 diabetes mellitus and evaluates the effect of vitamin D
      supplementation on glycaemic markers in this population. Literature searches were
      performed in the BIREME, LILACS, and PubMed databases using the Medical Subject
      Headings and words related to vitamin D, type 2 diabetes mellitus, and glycaemic
      control. Interventional and observational studies were considered eligible. The
      evaluation of the included studies was independently performed by 2 evaluators at
      all stages of selection, data extraction, and bias risk assessment. The primary
      outcome was the relationship between vitamin D levels and glucose metabolism
      markers in type 2 diabetes mellitus individuals. The secondary outcome was the
      effect of vitamin D supplementation on the glycaemic control markers in
      individuals with type 2 diabetes mellitus. The inverse relationship between
      vitamin D and variables of glucose metabolism was verified. Interventional
      studies revealed that vitamin D supplementation did not alter glycaemic control
      markers in most studies. Few studies have shown positive effects with a
      significant reduction in the percentage of glycated haemoglobin, insulin, and
      glucose concentrations, and changes in homeostatic model assessment-insulin
      resistance and beta cell, and quantitative insulin sensitivity check index.
      Therefore, despite the association of vitamin D with glucose metabolism, there is
      insufficient evidence of the beneficial effects of its supplementation on the
      metabolic control of type 2 diabetes mellitus.

PMID- 29172026
TI  - Effect of non-prohibited drugs on the phase II metabolic profile of morphine. An
      in vitro investigation for doping control purposes.
AB  - The potential consequences of drug-drug interaction on the strategies adopted by
      anti-doping laboratories to report an adverse analytical finding for morphine
      were investigated. We evaluated in vitro the effects of 14 drugs on the principal
      metabolic pathways of morphine. The selected drugs are among those most commonly
      used by the athletes, none of them presently included in the World Anti-Doping
      Agency (WADA) Prohibited List. The non-prohibited drugs included 4 antifungals
      (fluconazole, itraconazole, ketoconazole, and miconazole), 6 benzodiazepines
      (alprazolam, bromazepam, clonazepam, lorazepam, lormetazepam, and triazolam), and
      4 non-steroidal anti-inflammatory drugs (diclofenac, ibuprofen, ketoprofen, and
      nimesulide). The in vitro assays were based on the use of either human liver
      microsomes or uridine 5'-diphospho-glucuronosyl-transferases. Morphine and its
      glucuronides were determined by developed liquid chromatography-mass spectrometry
      procedure after dilution with an aqueous solution containing their deuterated
      isotopologues as internal standards. Morphine is mainly excreted as phase II
      metabolites: about 70% of the parent compound is found to be biotransformed by
      UGT2B7 to morphine-3-glucuronide (6065%) and morphine-6-glucuronide (5-10%). A
      reduction of the enzymatic activity of the UGT2B7 was recorded in the presence of
      9 of the 14 drugs under investigation (ketoconazole, miconazole, itraconazole,
      diclofenac, ibuprofen, clonazepam, lorazepam, lormetazepam, and triazolam), with
      a consequent significant reduction of the levels of the glucuronide metabolites.
      This phenomenon in vivo may affect the rate of the urinary excretion of morphine
      with the risk of reporting "false negative" results, especially in case of
      results close to the decision limit value set by WADA.

PMID- 29172027
TI  - An enhanced chemoenzymatic method for loading substrates onto carrier protein
      domains.
AB  - Non-ribosomal peptide synthetase (NRPS) machineries produce many medically
      relevant peptides that cannot be easily accessed by chemical synthesis. Thus,
      understanding NRPS mechanism is of crucial importance to allow efficient redesign
      of these machineries to produce new compounds. During NRPS-mediated synthesis,
      substrates are covalently attached to peptidyl carrier proteins (PCPs), and
      studies of NRPSs are impeded by difficulties in producing PCPs loaded with
      substrates. Different approaches to load substrates onto PCP domains have been
      described, but all suffer from difficulties in either the complexity of chemical
      synthesis or low enzymatic efficiency. Here, we describe an enhanced
      chemoenzymatic loading method that combines 2 approaches into a single, highly
      efficient one-pot loading reaction. First, d-pantetheine and ATP are converted
      into dephospho-coenzyme A via the actions of 2 enzymes from coenzyme A (CoA)
      biosynthesis. Next, phosphoadenylates are dephosphorylated using alkaline
      phosphatase to allow linker attachment to PCP domain by Sfp mutant R4-4, which is
      inhibited by phosphoadenylates. This route does not depend on activity of the
      commonly problematic dephospho-CoA kinase and, therefore, offers an improved
      method for substrate loading onto PCP domains.

PMID- 29172028
TI  - Neural adaptations in quadriceps muscle after 4 weeks of local vibration training
      in young versus older subjects.
AB  - This study investigated the effects of a 4-week local vibration training (LVT) on
      the function of the knee extensors and corticospinal properties in healthy young
      and older subjects. Seventeen subjects (9 young and 8 older) performed 3 testing
      sessions: before (PRE1) and after (PRE2) a 4-week resting period to control the
      repeatability of the data as well as after the LVT (POST). Jump performance,
      maximal voluntary contraction (MVC) and electromyographic (EMG) activity on
      vastus lateralis and rectus femoris muscles were assessed. Single-pulse
      transcranial magnetic stimulation (TMS) allowed evaluation of cortical voluntary
      activation (VATMS), motor evoked potential (MEP) area, and silent period (SP)
      duration. All training adaptations were similar between young and older subjects
      (p > 0.05) and the following results reflect the pooled sample of subjects. MVC
      (+11.9% +/- 8.0%, p < 0.001) and VATMS (+3.6% +/- 5.2%, p = 0.004) were
      significantly increased at POST compared with PRE2. Maximal vastus lateralis EMG
      was significantly increased at POST (+21.9% +/- 33.7%, p = 0.03). No changes were
      reported for MEPs on both muscles (p > 0.05). SPs recorded during maximal and
      submaximal contractions decreased in both muscles at POST (p < 0.05). Vertical
      jump performance was increased at POST (p < 0.05). LVT seems as effective in
      young as in older subjects to improve maximal functional capacities through
      neural modulations occurring at least partly at the supra-spinal level. Local
      vibration may be used as an efficient alternative training method to improve
      muscular performance in both healthy young and older subjects.

PMID- 29172029
TI  - Decreasing sprint duration from 20 to 10 s during reduced-exertion high-intensity
      interval training (REHIT) attenuates the increase in maximal aerobic capacity but
      has no effect on affective and perceptual responses.
AB  - Recent studies have demonstrated that modifying the "classic" 6 * 30-s "all-out"
      sprint interval training protocol by incorporating either shorter sprints (6 * 10
      s or 15-s sprints) or fewer sprints (e.g., 2 * 20-s sprints; reduced-exertion
      high-intensity interval training (REHIT)) does not attenuate the training-induced
      improvements in maximal aerobic capacity. The aim of the present study was to
      determine if reducing the sprint duration in the REHIT protocol from 20 s to 10 s
      per sprint influences acute affective responses and the change in maximal aerobic
      capacity following training. Thirty-six sedentary or recreationally active
      participants (17 women; mean +/- SD; age: 22 +/- 3 years; body mass index: 24.5
      +/- 4.6 kg.m-2; maximal aerobic capacity: 37 +/- 8 mL.kg-1.min-1) were randomised
      to a group performing a "standard" REHIT protocol involving 2 * 20-s sprints or a
      group who performed 2 * 10-s sprints. Maximal aerobic capacity was determined
      before and after 6 weeks of 3 weekly training sessions. Acute affective responses
      and perceived exertion were assessed during training. Greater increases in
      maximal aerobic capacity were observed for the group performing 20-s sprints
      (2.77 +/- 0.75 to 3.04 +/- 0.75 L.min-1; +10%) compared with the group performing
      10-s sprints (2.58 +/- 0.57 vs. 2.67 +/- 3.04 L.min-1; +4%; group * time
      interaction effect: p < 0.05; d = 1.06). Positive affect and the mood state
      vigour increased postexercise, while tension, depression, and total mood
      disturbance decreased, and negative affect remained unchanged. Affective
      responses and perceived exertion were not altered by training and were not
      different between groups. In conclusion, reducing sprint duration in the REHIT
      protocol from 20 s to 10 s attenuates improvements in maximal aerobic capacity,
      and does not result in more positive affective responses or lower perceived
      exertion.

PMID- 29172030
TI  - Omega-3 Fatty Acids in Maternity and Neonatal Care.

PMID- 29172031
TI  - Close Resection Margins Do Not Influence Local Recurrence in Patients With Oral
      Squamous Cell Carcinoma: A Prospective Cohort Study.
AB  - PURPOSE: This study investigated the clinical relevance of the distance between
      the resection margin and tumor cells of the primary sites for oral squamous cell
      carcinoma, with particular attention to local recurrence rate. PATIENTS AND
      METHODS: All patients diagnosed with oral squamous cell carcinoma from 1995 to
      2006 and treated primarily with surgery formed the initial cohort of the study.
      Patient with various degrees of dysplasia in the margin, patients who received
      radiotherapy, and patients who died of causes other than oral cancer were
      excluded. Margins 1 to 5 mm were considered close. A margin of at least 5 mm was
      considered free of disease (clear). Local recurrence was defined as tumor
      development at the site of the primary tumor during the follow-up period (>=5
      yr). The Fisher exact test was used to determine the relevance of the differences
      between the studied groups (free vs close margins) in relation to local
      recurrence. RESULTS: Histologic analysis of the specimens was performed. Of the
      53 patients, 32 had free margins and 3 of the 32 had a local recurrence. In
      addition, 21 patients had close margins and 3 of the 21 had a local recurrence.
      The difference between the 2 groups was not statistically relevant. CONCLUSIONS:
      The authors advocate that the strategy of using close resection margins as a
      generic indicator for local recurrence and adverse prognosis might have to be
      reassessed. The histopathologic evidence of tumor cells within a distance less
      than 0.5 cm from the surgical margins does not necessarily seem to offer a
      certain indication for additional treatment. Other prognostic factors, such as
      involvement of cervical lymph nodes and tumor depth, must be considered in the
      decision making for further treatment.

PMID- 29172032
TI  - Galactomannan use in clinical practice: providing free testing is not the full
      answer.
AB  - INTRODUCTION: Invasive aspergillosis is a condition associated with a high
      mortality rate mostly due to difficulties in performing an early diagnosis. In
      recent years, galactomannan detection has markedly improved the diagnosis of
      invasive aspergillosis, but very little is known on how physicians deal with this
      test in clinical practice. METHODS: This cross-sectional study aimed to analyze
      the indications for the use of serum galactomannan in a large Brazilian hospital,
      between 2015 and 2016. No specific protocol was in place for GM request. We
      reviewed the medical records of adult (>18 years-old) patients who were tested
      for galactomannan due to one the following indications: screening, diagnosis, or
      treatment follow-up. Additional variables included demographic data, underlying
      diseases, presence of neutropenia, and use of previous antifungal (anti
      Aspergillus) drugs. RESULTS: The mean age of the patients was 51 years-old (sd+/
      15.8), and 63.3% of patients were male. Patients with hematological malignancies
      accounted for 60.1% of the cases, mostly acute myeloid leukemia (19.6%).
      Galactomannan testing was positive in 12.2% of patients, including 1.6% of
      occasions in which the test was used for screening purposes, 13.2% for diagnosis,
      and 32.4% during follow-up. Median time for chest imaging request was two days
      before GM testing. Previous antifungal therapy was reported for 35.1% of
      patients, mostly amphotericin B (57.1%). CONCLUSION: The correct use of
      galactomannan testing is essential for an early diagnosis of invasive
      aspergillosis, which may improve the prognosis of the disease. We demonstrated
      that clinicians usually ask for galactomannan tests to confirm imaging findings
      in patients who frequently were on antifungal drugs, something that could be
      improved by medical education. We observed a low frequency of galactomannan use
      for preemptive antifungal therapy (25.7%), which is worrying considering the well
      known beneficial use of GM testing in this scenario.

PMID- 29172033
TI  - In vitro antifungal susceptibility of clinical and environmental isolates of
      Aspergillus fumigatus and Aspergillus flavus in Brazil.
AB  - The in vitro susceptibility of 105 clinical and environmental strains of
      Aspergillus fumigatus and Aspergillus flavus to antifungal drugs, such as
      amphotericin B, azoles, and echinocandins was evaluated by the broth
      microdilution method proposed by the European Committee on Antimicrobial
      Susceptibility Testing (EUCAST). Following the EUCAST-proposed breakpoints, 20%
      and 25% of the clinical and environmental isolates of A. fumigatus, respectively,
      were found to be resistant to itraconazole (Minimal Inhibitory Concentration,
      MIC>2.0mg/L). Voriconazole showed good activity against A. fumigatus and A.
      flavus strains, except for one clinical strain of A. fumigatus whose MIC was
      4.0mg/L. Posaconazole (<=0.25mg/L) also showed appreciable activity against both
      species of Aspergillus, except for six A. fumigatus strains with relatively
      higher MICs (0.5mg/L). The MICs for Amphotericin B ranged from 0.06 to 1.0mg/L
      for A. fumigatus, but were much higher (0.5-8.0mg/L) for A. flavus. Among the
      echinocandins, caspofungin showed a geometric mean of 0.078 and 0.113 against the
      clinical and environmental strains of A. flavus, respectively, but had elevated
      minimal effective concentrations (MECs) for seven of the A. fumigatus strains.
      Anidulafungin and micafungin exhibited considerable activity against both A.
      fumigatus and A. flavus isolates, except for one environmental isolate of A.
      fumigatus that showed an MEC of 1mg/L to micafungin. Our study proposes that a
      detailed investigation of the antifungal susceptibility of the genus Aspergillus
      from different regions of Brazil is necessary for establishing a response profile
      against the different classes of antifungal agents used in the treatment of
      aspergillosis.

PMID- 29172034
TI  - Development of mannose functionalized dendrimeric nanoparticles for targeted
      delivery to macrophages: use of this platform to modulate atherosclerosis.
AB  - Dysfunctional macrophages underlie the development of several diseases including
      atherosclerosis where accumulation of cholesteryl esters and persistent
      inflammation are 2 of the critical macrophage processes that regulate the
      progression as well as stability of atherosclerotic plaques. Ligand-dependent
      activation of liver-x-receptor (LXR) not only enhances mobilization of stored
      cholesteryl ester but also exerts anti-inflammatory effects mediated via trans
      repression of proinflammatory transcription factor nuclear factor kappa B.
      However, increased hepatic lipogenesis by systemic administration of LXR ligands
      (LXR-L) has precluded their therapeutic use. The objective of the present study
      was to devise a strategy to selectively deliver LXR-L to atherosclerotic plaque
      associated macrophages while limiting hepatic uptake. Mannose-functionalized
      dendrimeric nanoparticles (mDNP) were synthesized to facilitate active uptake via
      the mannose receptor expressed exclusively by macrophages using polyamidoamine
      dendrimer. Terminal amine groups were used to conjugate mannose and LXR-L T091317
      via polyethylene glycol spacers. mDNP-LXR-L was effectively taken up by
      macrophages (and not by hepatocytes), increased expression of LXR target genes
      (ABCA1/ABCG1), and enhanced cholesterol efflux. When administered intravenously
      to LDLR-/- mice with established plaques, significant accumulation of
      fluorescently labeled mDNP-LXR-L was seen in atherosclerotic plaque-associated
      macrophages. Four weekly injections of mDNP-LXR-L led to significant reduction in
      atherosclerotic plaque progression, plaque necrosis, and plaque inflammation as
      assessed by expression of nuclear factor kappa B target gene matrix
      metalloproteinase 9; no increase in hepatic lipogenic genes or plasma lipids was
      observed. These studies validate the development of a macrophage-specific
      delivery platform for the delivery of anti-atherosclerotic agents directly to the
      plaque-associated macrophages to attenuate plaque burden.

PMID- 29172036
TI  - Editorial Comment.

PMID- 29172037
TI  - Editorial Comment.

PMID- 29172038
TI  - Musculoskeletal pain and musculoskeletal syndromes in adolescents are related to
      electronic devices.
AB  - OBJECTIVE: To evaluate television and simultaneous electronic devices use in
      adolescents with musculoskeletal pain and musculoskeletal pain syndromes.
      METHODS: A cross-sectional study was performed in 299 healthy adolescents of a
      private school. All students completed a self-administered questionnaire,
      including: demographic data, physical activities, musculoskeletal pain symptoms,
      and use of simultaneous television/electronic devices (computer, internet,
      electronic games, and cell phones). Seven musculoskeletal pain syndromes were
      also evaluated: juvenile fibromyalgia, benign joint hypermobility syndrome,
      myofascial syndrome, tendinitis, bursitis, epicondylitis, and complex regional
      pain syndrome. RESULTS: Inter-rater agreement between pretest and retest was
      0.83. Musculoskeletal pain and musculoskeletal pain syndrome were found in
      183/299 (61%) and 60/183 (33%), respectively. The median age (15 [10-18] vs. 14
      [10-18] years, p=0.032) and years of education (10 [5-12] vs. 9 [5-12] years,
      p=0.011) were significantly higher in adolescents with musculoskeletal pain when
      compared with those without this condition. The frequencies of female gender (59%
      vs. 47%, p=0.019), cell phone use (93% vs. 81%, p=0.003), and simultaneous use of
      at least two electronic devices (80% vs. 67%, p=0.011) were significantly higher
      in the former group. Further comparisons between adolescents with and without
      musculoskeletal pain syndromes revealed that the frequency of female gender was
      significantly higher in the former group (75% vs. 25%, p=0.002), and with a
      significantly reduced median of weekends/holidays electronic games use (1.5 [0
      10] vs. 3 [0-17]h/day, p=0.006). CONCLUSIONS: A high prevalence of
      musculoskeletal pain/syndromes was observed in female adolescents.
      Musculoskeletal pain was mostly reported at a median age of 15 years, and
      students used at least two electronic devices. Reduced use of electronic games
      was associated with musculoskeletal pain syndromes.

PMID- 29172035
TI  - Macrophages under pressure: the role of macrophage polarization in hypertension.
AB  - Hypertension is a multifactorial disease involving the nervous, renal, and
      cardiovascular systems. Macrophages are the most abundant and ubiquitous immune
      cells, placing them in a unique position to serve as key mediators between these
      components. The polarization of macrophages confers vast phenotypic and
      functional plasticity, allowing them to act as proinflammatory, homeostatic, and
      anti-inflammatory agents. Key differences between the M1 and M2 phenotypes, the 2
      subsets at the extremes of this polarization spectrum, place macrophages at a
      juncture to mediate many mechanisms involved in the pathogenesis of hypertension.
      Neuronal and non-neuronal regulation of the immune system, that is, the
      "neuroimmuno" axis, plays an integral role in the polarization of macrophages. In
      hypertension, the neuroimmuno axis results in synchronization of macrophage
      mobilization from immune cell reservoirs and their chemotaxis, via increased
      expression of chemoattractants, to end organs critical in the development of
      hypertension. This complicated system is largely coordinated by the dichotomous
      actions of the autonomic neuronal and non-neuronal activation of cholinergic,
      adrenergic, and neurohormonal receptors on macrophages, leading to their ability
      to "switch" between phenotypes at sites of active inflammation. Data from
      experimental models and human studies are in concordance with each other and
      support a central role for macrophage polarization in the pathogenesis of
      hypertension.

PMID- 29172039
TI  - Health-related quality of life in patients with bronchiolitis obliterans.
AB  - OBJECTIVE: To evaluate the overall health-related quality of life in patients
      with bronchiolitis obliterans. METHODS: Participants with a diagnosis of post
      infectious bronchiolitis obliterans, who were being followed-up at two
      specialized outpatient clinics of Pediatric Pulmonology in Porto Alegre, Brazil,
      and controls aged between 8 and 17 years, of both genders, were included in the
      study. Controls were paired by gender, age, and socioeconomic level in relation
      to the group of participants with post-infectious bronchiolitis obliterans. The
      version of the Pediatric Quality of Life Inventory (PedsQ) tool validated for
      Brazil was applied for the assessment of Health-related Quality of Life, through
      an interview. The comparison of the Health-related Quality of Life means between
      the groups was performed using Student's t-test for independent samples and the
      chi-squared test, for categorical variables. RESULTS: 34 patients diagnosed with
      post-infectious bronchiolitis obliterans and 34 controls participated in the
      study. The mean age of the children included in the study was 11.2+/-2.5 years,
      and 49 (72%) of them were males. The groups showed no significant differences in
      relation to these variables. The quality of life score was significantly and
      clinically lower in the post-infectious bronchiolitis obliterans group when
      compared with controls in the health (72.36+/-15.6, 81.06+/-16.4, p=0.031) and
      school domains (62.34+/-20.7, 72.94+/-21.3, p=0.043), as well as in the total
      score (69.53+/-14.9, 78.02+/-14.8, p=0.024), respectively. CONCLUSION: Patients
      with post-infectious bronchiolitis obliterans presented lower health-related
      quality of life scores when compared with healthy individuals in the total score
      and in the health and school domains.

PMID- 29172040
TI  - Effect of long-term fertilization on humic redox mediators in multiple microbial
      redox reactions.
AB  - This study investigated the effects of different long-term fertilizations on
      humic substances (HSs), humic acids (HAs) and humins, functioning as redox
      mediators for various microbial redox biotransformations, including
      2,2',4,4',5,5'- hexachlorobiphenyl (PCB153) dechlorination, dissimilatory iron
      reduction, and nitrate reduction, and their electron-mediating natures. The redox
      activity of HSs for various microbial redox metabolisms was substantially
      enhanced by long-term application of organic fertilizer (pig manure). As a redox
      mediator, only humin extracted from soils with organic fertilizer amendment (OF
      HM) maintained microbial PCB153 dechlorination activity (1.03 MUM PCB153
      removal), and corresponding HA (OF-HA) most effectively enhanced iron reduction
      and nitrate reduction by Shewanella putrefaciens. Electrochemical analysis
      confirmed the enhancement of their electron transfer capacity and redox
      properties. Fourier transform infrared analysis showed that C=C and C=O bonds,
      and carboxylic or phenolic groups in HSs might be the redox functional groups
      affected by fertilization. This research enhances our understanding of the
      influence of anthropogenic fertility on the biogeochemical cycling of elements
      and in situ remediation ability in agroecosystems through microorganisms'
      metabolisms.

PMID- 29172041
TI  - Airborne microplastics: Consequences to human health?
AB  - Microplastics have recently been detected in atmospheric fallout in Greater
      Paris. Due to their small size, they can be inhaled and may induce lesions in the
      respiratory system dependent on individual susceptibility and particle
      properties. Even though airborne microplastics are a new topic, several
      observational studies have reported the inhalation of plastic fibers and
      particles, especially in exposed workers, often coursing with dyspnea caused by
      airway and interstitial inflammatory responses. Even though environmental
      concentrations are low, susceptible individuals may be at risk of developing
      similar lesions. To better understand airborne microplastics risk to human
      health, this work summarizes current knowledge with the intention of developing
      awareness and future research in this area.

PMID- 29172042
TI  - The transformation of triclosan by laccase: Effect of humic acid on the reaction
      kinetics, products and pathway.
AB  - This study systematically explored the effect of humic acid (HA) (as model of
      natural organic matter) on the kinetics, products and transformation pathway of
      triclosan (TCS) by laccase-catalyzed oxidation. It was found that TCS could be
      effectively transformed by laccase-catalysis, with the apparent second-order rate
      constant being 0.056 U-1 mL min-1. HA inhibited the removal rate of TCS. HA
      induced inhibition was negatively correlated with HA concentration in the range
      of 0-10 mg L-1 and pH-dependent from 3.5 to 9.5. FT-IR and 13C NMR spectra showed
      a decrease of aromatic hydroxyl (phenolic) groups and an increase of aromatic
      ether groups, indicating the cross-linking of HA via C-O-C and C-N-C bonds during
      enzyme-catalyzed oxidation. Ten principle oxidative products, including two
      quinone-like products (2-chlorohydroquinone, 2-chloro-5-(2,4
      dichlodichlorophenoxy)-(1,4)benzoquinone), one chlorinated phenol (2,4
      dichlorophenol (2,4-DCP)), three dimers, two trimmers and two tetramers, were
      detected by gas chromatograghy/mass spectrometry (GC-MS) and high performance
      liquid chromatography/quadrupole time-of-flight/mass spectrometry (HPLC/Q
      TOF/MS). The presence of HA induced significantly lesser generation of self
      polymers and enhanced cross-coupling between HA and self-polymers via C-O-C, C-N
      C and C-C coupling pathways. A plausible transformation pathway was proposed as
      follows: TCS was initially oxidized to form reactive phenoxyl radicals, which
      self-coupled to each other subsequently by C-C and C-O pathway, yielding self
      polymers. In addition, the scission of ether bond was also observed. The presence
      of HA can promote scission of ether bond and further oxidation of phenoxyl
      radicals, forming hydroxylated or quinone-like TCS. This study shed light on the
      behavior of TCS in natural environment and engineered processes, as well provided
      a perspective for the water/wastewater treatment using enzyme-catalyzed oxidation
      techniques.

PMID- 29172043
TI  - Polycyclic aromatic hydrocarbons in fruits and vegetables: Origin, analysis, and
      occurrence.
AB  - Feed intake, for non-smokers, is the first route of contamination to polycyclic
      aromatic hydrocarbons (PAHs), which are potentially toxic compounds via
      ingestion. Investigations are focused on the presence of PAHs in fruits and
      vegetables. Transfer of PAHs can occur from air and soil during cultivation. They
      can also appear prior to consumption during storage, transport or cooking
      processes. Rather low amounts of PAHs are usually detected in raw fruits and
      vegetables. Quantities are between 0.01 and 0.5 MUg kg-1 (wet weight) for
      compounds classified as priority pollutants by the US Environmental Protection
      Agency (EPA). However, several studies point out that concentrations of some PAHs
      can exceed 0.5 MUg kg-1 wet weight in diverse fruits and vegetables and even
      reach 5 MUg kg-1. Amounts can be very different depending on the surrounding area
      of the crops, the aromatic hydrocarbon, or even the product itself. PAHs content
      is usually higher for products grown near roadways or in urban regions than in
      rural areas. Trace level of compounds such as phenanthrene, fluoranthene and
      pyrene have been found in quite every raw fruit and vegetable. Relative high
      amounts of lighter PAHs such as naphthalene, acenaphthylene, and acenaphthene
      have been found in some of them.

PMID- 29172044
TI  - Investigation on the wrong way driving crash patterns using multiple
      correspondence analysis.
AB  - Wrong way driving (WWD) has been a constant traffic safety problem in certain
      types of roads. Although these crashes are not large in numbers, the outcomes are
      usually fatalities or severe injuries. Past studies on WWD crashes used either
      descriptive statistics or logistic regression to determine the impact of key
      contributing factors. In conventional statistics, failure to control the impact
      of all contributing variables on the probability of WWD crashes generates bias
      due to the rareness of these types of crashes. Distribution free methods, such as
      multiple correspondence analysis (MCA), overcome this issue, as there is no need
      of prior assumptions. This study used five years (2010-2014) of WWD crashes in
      Louisiana to determine the key associations between the contribution factors by
      using MCA. The findings showed that MCA helps in presenting a proximity map of
      the variable categories in a low dimensional plane. The outcomes of this study
      are sixteen significant clusters that include variable categories like determined
      several key factors like different locality types, roadways at dark with no
      lighting at night, roadways with no physical separations, roadways with higher
      posted speed, roadways with inadequate signage and markings, and older drivers.
      This study contains safety recommendations on targeted countermeasures to avoid
      different associated scenarios in WWD crashes. The findings will be helpful to
      the authorities to implement appropriate countermeasures.

PMID- 29172045
TI  - Interactive risk analysis on crash injury severity at a mountainous freeway with
      tunnel groups in China.
AB  - Traffic safety of freeways has attracted major concerns, especially for a
      mountainous freeway affected by adverse terrain conditions, constrained roadway
      geometry and complicated driving environments. On the basis of a comprehensive
      dataset collected from a mountainous freeway with a length of 61km but gathering
      12 tunnels, this study seeks to examining the interactive effect of mountainous
      freeway alignment, driving behaviors, vehicle characteristics and environmental
      factors on crash severity. A classification and regression tree (CART) model is
      employed as it can deal with high-order interactions between explanatory
      variables. Results show that the driving behavior is the most important
      determinant for injury severity of mountainous freeway crashes, followed by the
      crash time, grade, curve radius and vehicle type. These variables, interacted
      with the factors of season and crash location, may largely account for the
      likelihood of high risk events which may result in severe crashes. Events
      associated with a notably higher probability of severe crashes include coach
      drivers involved in improper lane changing and other improper actions, drivers
      involved in speeding during afternoon or evening, drivers involved in speeding
      along large curve and straight segment during morning, noon or night, and drivers
      involved in fatigue while passing along the downgrade. Safety interventions to
      prevent severe crashes at the mountainous freeway include hierarchical
      supervision in terms of hazardous driving events, enhanced enforcement for
      speeding and fatigue driving, deployment of advanced driving assistance systems
      for fatigue driving warning, and cumulative driving time monitoring for long
      distance-travel freight vehicles.

PMID- 29172046
TI  - Evaluating the effect of lane width and roadside configurations on speed, lateral
      position and likelihood of comfortable overtaking in exclusive motorcycle lane.
AB  - Construction of exclusive motorcycle lanes is one of the measures to reduce
      motorcycle fatalities. Previous studies highlighted the risk of crashes with
      roadside objects and the tendency of motorcyclists to ride with excessive speed
      on exclusive motorcycle lanes. However, the risk of same-direction crashes on
      exclusive motorcycle lanes was not explored in much detail, especially on the
      impact of lane geometry and roadside configurations. This study used naturalistic
      riding data to determine the effects of lane width and roadside configurations on
      overtaking speed, lateral position and likelihood of comfortable overtaking on
      tangential sections of an exclusive motorcycle lane. Twenty-nine recruited
      motorcyclists rode the instrumented motorcycles along a 20km stretch of an
      exclusive motorcycle lane along a major urban road. Results revealed that both
      the roadside configurations and lane width significantly affect the participants'
      lateral position, while the roadside configurations only affects the overtaking
      speed. Participants' overtaking speeds and the front motorcycles' lateral
      position contribute significantly to the likelihood of comfortable overtaking in
      exclusive motorcycle lanes. The findings highlight the importance of micro-level
      behavior indicators in improving the design and overall safety of the exclusive
      motorcycle facility.

PMID- 29172047
TI  - Unhealthy assimilation or persistent health advantage? A longitudinal analysis of
      immigrant health in the United States.
AB  - Existing evidence on immigrant health assimilation, which is largely based on
      cross-sectional data, suggests that immigrants' initial health advantage erodes
      over time. This study uses longitudinal data to directly compare the self-rated
      health trajectories of immigrants and the native-born population. Data come from
      four panels of the Survey of Income and Program Participation (1996, 2001, 2004,
      and 2008), with each panel containing 2-4 years of health information. Results
      show that immigrants' self-rated health remained stable during the period under
      study, but there was a concomitant decline in health for the native-born
      population. This result pointed to a persistent health advantage of immigrants
      during the period under study. The pattern held for immigrants of different
      length of residence and was especially salient for those originally from Latin
      America and Asia. Our findings that immigrants maintain their health advantage do
      not support the pattern of unhealthy assimilation commonly reported in cross
      sectional studies.

PMID- 29172048
TI  - Life events in schizoaffective disorder: A systematic review.
AB  - BACKGROUND: Life events play a central role in the development of psychiatric
      disorders and impact course and outcome. We present a systematic review of the
      literature on the relationship of life events with the onset and long-term course
      of schizoaffective disorder. METHODS: MEDLINE was searched with the combination
      of the key words: 'life events' plus 'schizoaffective'. The PRISMA method was
      followed in the review process. RESULTS: From the identified 66 papers only 12
      were considered to be of relevance to the current study and 6 more papers were
      identified by inspecting the reference lists of the identified papers.
      LIMITATIONS: There are very few studies focusing on the role of life events in
      schizoaffective disorder indicating insufficient data concerning the relationship
      of life events with onset and long-term course of schizoaffective disorder.
      Reported effects are not generic but concern specific events like the loss of
      mother, and females seem to be more vulnerable. Patients with schizoaffective
      disorder manifest high rates of PTSD. CONCLUSION: The literature on life events
      with the development and course of schizoaffective disorder is limited and
      precludes solid conclusions.

PMID- 29172049
TI  - Emotion regulation strategies moderate the relationship of fatigue with
      depersonalization and derealization symptoms.
AB  - BACKGROUND: The aim of the present study was to investigate the relationships of
      common emotion regulation strategies (suppression and reappraisal) to self
      reported fatigue and depersonalization/derealization symptoms. Specifically, we
      tested the moderating effect of suppression and reappraisal on the link of
      fatigue with depersonalization and derealization symptoms. Opposite effects were
      expected for both emotion regulation strategies assuming that cognitive
      reappraisal has an adaptive buffering effect, while suppression intensifies the
      association of fatigue and depersonalization/derealization experiences. METHODS:
      In a representative study (N = 2524) we assessed emotion regulation strategies,
      fatigue, depersonalization/derealization, distress, and demographic variables via
      questionnaires. 55.5% of the participants were female, mean age was 49.4 (SD =
      18.2) years with age groups represented in comparable proportions. RESULTS: In
      line with the assumptions, moderated regression analyses revealed an interaction
      effect of emotion regulation strategies and fatigue. Simple slope analyses
      indicated a buffering effect of cognitive reappraisal on the positive relation of
      fatigue with depersonalization and derealization symptoms. In contrast,
      suppression fosters the positive correlation of fatigue and depersonalization and
      derealization experiences. LIMITATIONS: Our study is limited to these two
      habitual emotion regulation strategies employing a cross sectional design.
      CONCLUSION: Our findings provide comprehensive empirical data investigating
      depersonalization/derealization symptoms from the perspective of emotion
      regulation research. Cognitive reappraisal might help people suffering from
      fatigue to prevent depersonalization and derealization tendencies.

PMID- 29172050
TI  - A longitudinal study of Latino and non-Hispanic mothers' and fathers' depressive
      symptoms and its association with parent-child communication.
AB  - BACKGROUND: Roughly 8% of the U.S. population report moderate or severe
      depression for two or more weeks and Latinos (3.7%) report higher rates of severe
      depression compared to non-Hispanic whites (2.6%) (Pratt and Brody, 2014). As the
      Latino population continues to grow in the U.S., there is little research on the
      manifestations for depression, and how this affects the family system
      longitudinally. METHODS: Based on data from the Fragile Families and Child
      Wellbeing Study, a 3-step latent class analysis examined the association of self
      reported parental depressive symptoms and their children's perceived levels of
      closeness and openness to communicate with their parents over 9 years (N=3956
      families). RESULTS: Latino parents reported four different depressive patterns,
      while non-Hispanic parents were more diversified and had six patterns in terms of
      latent class analysis. Latinos reported episodic symptoms, while NH parents were
      more likely to report chronic depressive symptoms over time. Regardless of
      race/ethnicity, parental depressive symptoms negatively affected their children's
      reported level of parental closeness and openness to communicate with mothers and
      fathers. LIMITATIONS: As with any self-report data, the risk of social
      desirability bias is likely still present. Additionally, these results cannot be
      generalized to the broader U.S. POPULATION:  CONCLUSIONS: Due to the different
      mental health presentations over 9 years, and following the federal initiatives
      (National Institute of Mental Health, 2015) of early and consistent surveillance,
      we advise that clinicians and primary care physicians screen for depressive
      symptoms at least yearly.

PMID- 29172052
TI  - Profiling risk for depressive disorder by circuit, behavior and self-report
      measures of emotion function.
AB  - BACKGROUND: Major depressive disorder (MDD) is characterized by maladaptions in
      affective brain circuitry and in emotion regulation. It remains unknown whether
      these maladaptions characterize first-degree relatives of probands who are
      unaffected yet have a higher risk of developing MDD. METHODS: Participants were
      72 unaffected first-degree relatives of probands with MDD and 66 matched non
      relative controls. We investigated brain circuit function and self-reported
      emotion regulation strategies for reappraisal and suppression. During functional
      magnetic resonance imaging, we probed circuitry relevant to both negative and
      positive valence systems using facial expressions signaling potential threat,
      sadness and happiness, presented under both conscious and subliminal viewing
      conditions. We compared groups using a statistically controlled region of
      interest (ROI) approach including the amygdala, insula, anterior cingulate cortex
      (ACC), ventromedial prefrontal cortex and dorsolateral prefrontal cortex. We also
      used a data-driven cluster analytic approach for characterizing the relatives by
      their brain function profiles. RESULTS: As a group, relatives were distinguished
      by hyper-reactivity of the pregenual ACC during subliminal viewing of threat
      related expressions but hypo-activation of the amygdala, insula and dorsal ACC
      during explicit viewing of the same threat-related expressions and sadness. When
      considered individually, this brain function profile characterized two-thirds of
      relatives, and these relatives were also less likely to use reappraisal to
      regulate negative emotion. LIMITATIONS: The design was cross-sectional and
      therefore does not provide direct evidence as to the trait- (versus state-) like
      profile observed in relatives. CONCLUSIONS: Familial risk for MDD may involve a
      disruption to the normal recruitment of neural circuits for appraising salient
      emotions, both implicit and explicit. Interventions targeting reappraisal
      strategies for regulating negative emotion may serve to buffer this risk.

PMID- 29172051
TI  - DNA methylation from birth to late adolescence and development of multiple-risk
      behaviours.
AB  - BACKGROUND: Risk behaviours in adolescence are linked to poor educational
      attainment and health and other outcomes in young adulthood. We explored whether
      there are molecular mechanisms associated with the development, or the result, of
      multiple risk behaviours (MRBs). METHODS: MRBs (antisocial behaviour and
      delinquency, traffic-related risk behaviour, risky sexual behaviour, lack of
      exercise) and their sumscore were characterized based on self-reported questions
      at age 7 and 17 within the ARIES subsample of the ALSPAC birth cohort, and were
      linked to DNA methylation at over 485,000 CpG sites at ages 0,7 and 17.
      Associations were determined for participants with complete data (n = 227-575).
      RESULTS: There was weak evidence of associations between cumulative MRBs and
      methylation at cg01783492 and cg16720578 at age 17. DNA methylation at age 17 was
      associated with risky sexual behaviour (cg22883332), lack of exercise
      (cg03152353, cg20056908, cg20571116) and substance use (cg02188400, cg13906377).
      No associations between DNA methylation and individual risk behaviours at age 7
      were observed. DNA methylation at age 7 might predispose for traffic-related risk
      behaviour (cg24683561) and substance use (cg08761410) at age 17. LIMITATIONS:
      Main limitations are absence of information on directly measured blood cell type
      proportions and tissue specificity, and a modest sample size. CONCLUSIONS:
      Cumulative MRB in late adolescence was associated with effects on DNA
      methylation. More specifically, risky sexual behaviour and sedentary behaviour
      are associated with changes in DNA methylation, while DNA methylation in
      childhood may predict later traffic-related risky behaviour. For substance use
      effects in both temporal directions were observed.

PMID- 29172053
TI  - Associations of neurofunctional, morphometric and metabolic abnormalities with
      clinical symptom severity and recognition deficit in obsessive-compulsive
      disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) causes neural dysfunction
      associated with cognitive deficit and emotional dysregulation. This study
      assessed the associations of the neurofunctional changes, gray matter (GM) and
      white matter (WM) volume alterations in conjunction with in vivo metabolic
      changes on the working memory tasks in patients with OCD. METHODS: Eighteen
      patients with OCD and 18 healthy controls matched for age, sex, and educational
      levels underwent high-resolution T1-weighted magnetic resonance imaging (MRI),
      event-related functional MRI (fMRI), and proton magnetic resonance spectroscopy
      (1H-MRS) at 3T. RESULTS: In fMRI, patients with OCD showed lower activities in
      the cerebellum, inferior temporal gyrus, orbitofrontal gyrus, dorsolateral
      prefrontal cortex and calcarine gyrus compared to the controls. In VBM, the
      patients showed significantly reduced GM volumes, especially in the cerebellum,
      hippocampus, and superior temporal gyrus, together with significantly reduced WM
      volumes in the retrolenticular part of the internal capsule, dorsolateral
      prefrontal cortex (DLPFC) and orbitofrontal gyrus. In 1H-MRS, the ratios of N
      acetylaspartate/creatine and choline/creatine were significantly lower in the
      DLPFC of the patients than in the controls, whereas the ratio of beta?gamma
      glutamine-glutamate/creatine was significantly higher in the patients than in the
      controls. LIMITATIONS: This study examined small numbers of subjects in each one
      of the groups. CONCLUSIONS: The findings will be helpful to aid us in
      understanding of neurocognitive impairment in OCD, and thus, enhancing the
      diagnostic accuracy for OCD by additional information on the associated brain
      functional deficit, cerebral volume change and metabolic abnormality.

PMID- 29172054
TI  - Mobile technology for medication adherence in people with mood disorders: A
      systematic review.
AB  - BACKGROUND: Medication non-adherence is a critical challenge for many patients
      diagnosed with mood disorders (Goodwin and Jamison, 1990). There is a need for
      alternative strategies that improve adherence among patients with mood disorders
      that are cost-effective, able to reach large patient populations, easy to
      implement, and that allow for communication with patients outside of in-person
      visits. Technology-based approaches to promote medication adherence are
      increasingly being explored to address this need. The aim of this paper is to
      provide a systematic review of the use of mobile technologies to improve
      medication adherence in patients with mood disorders. METHODS: A total of nine
      articles were identified as describing mobile technology targeting medication
      adherence in mood disorder populations. RESULTS: Results showed overall
      satisfaction and feasibility of mobile technology, and reduction in mood
      symptoms; however, few examined effectiveness of mobile technology improving
      medication adherence through randomized control trials. LIMITATIONS: Given the
      limited number of studies, further research is needed to determine long term
      effectiveness. CONCLUSIONS: Mobile technologies has the potential to improve
      medication adherence and can be further utilized for symptom tracking, side
      effects tracking, direct links to prescription refills, and provide patients with
      greater ownership over their treatment progress.

PMID- 29172055
TI  - Offspring of depressed and anxious patients: Help-seeking after first onset of a
      mood and/or anxiety disorder.
AB  - BACKGROUND: Offspring of patients with depressive and/or anxiety disorders are at
      high risk of developing a similar disorder themselves. Early recognition and
      treatment may have substantial effects on prognosis. The main aim of this study
      was to examine the time to initial help-seeking and its determinants in offspring
      after the first onset of a mood and/or anxiety disorder. METHODS: Data are
      presented of 215 offspring with a mood and/or anxiety disorder participating in a
      cohort study with 10 year follow-up. We determined age of disorder onset and age
      of initial help-seeking. Offspring characteristics (gender, IQ, age of onset,
      disorder type, suicidal ideation) and family characteristics (socioeconomic
      status, family functioning) were investigated as potential predictors of the time
      to initial help-seeking. RESULTS: The estimated overall proportion of offspring
      of depressed/anxious patients who eventually seek help after onset of a mood
      and/or anxiety disorder was 91.9%. The time to initial help-seeking was more than
      two years in 39.6% of the offspring. Being female, having a mood disorder or
      comorbid mood and anxiety disorder (relative to anxiety) and a disorder onset in
      adolescence or adulthood (relative to childhood) predicted a shorter time to
      initial help-seeking. LIMITATIONS: Baseline information relied on retrospective
      reports. Age of onsets and age of initial help-seeking may therefore be subject
      to recall bias. CONCLUSION: Although most offspring eventually seek help after
      onset of a mood/anxiety disorder, delays in help-seeking were common, especially
      in specific subgroups of patients. This information may help to develop targeted
      strategies to reduce help-seeking delays.

PMID- 29172056
TI  - Electroconvulsive therapy and age: Age-related clinical features and
      effectiveness in treatment resistant major depressive episode.
AB  - OBJECTIVE: This study was aimed to compare clinical features, treatments outcomes
      and tolerability between young (18-45 years), middle age (46-64 years) and old
      (>= 65 years) patients treated with bilateral ECT for treatment resistant major
      depressive episode. METHOD: 402 patients were evaluated 1 day prior to ECT and a
      week after the treatment termination using the Clinical Global Impression Scale
      (CGI), the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Brief
      Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS) and the Mini
      Mental State Examination (MMSE). Response was defined as a reduction of at least
      50% from baseline on the HAM-D-17 score. Remission was defined as a score <= 7 on
      the HAM-D-17 at the final evaluation. RESULTS: Rates of response were not
      statistically different in the three groups (69.6% in old versus 63.5% in young
      and 55.5% in middle age groups). No significant differences were also observed in
      the proportions of remitters between the age groups (31.4% in young group, 27.7%
      in middle age group and 29.3% in old group). One week after the end of the ECT
      course the middle and old age groups showed a statistically significant increase
      in the MMSE score compared to baseline. We did not find significant differences
      between the three age groups in rates of premature drops-out due to ECT-related
      side effects. CONCLUSION: Our data support the use of ECT in elderly patients
      with treatment-resistant major depressive episode, with rates of response around
      70% and effectiveness being independent from age. In the old age group the
      baseline cognitive impairment improved after ECT and no life-threatening adverse
      event was detected.

PMID- 29172057
TI  - Dialogic oral exam in nursing education: A qualitative study of nursing students'
      perceptions.
AB  - The purpose of this articl is to explore nursing students' experiences of
      dialogic group oral exams used in the assessment of a medical nursing course. We
      discuss a small-group, educator-facilitated exam (dialogue exam). The data were
      gathered in April 2015 via an online survey including open questions. The
      participants were nursing students (n = 58) at a University of Applied Sciences.
      The data were subjected to inductive content analysis. The results suggest that
      students' experiences of the dialogue exam can be represented by four themes:
      context bound dynamics, new shared understanding, verified competences and
      holistic nursing care. The students liked the dialogue exam format, preferring it
      to the traditional individual written exam. The prerequisite for successful use
      of the dialogue exam format is that candidates perceived the exam situation as
      safe. Students need to be given information about the schedule and assessment
      criteria beforehand and should have some experience of the format.

PMID- 29172058
TI  - Rapid and simplified synthesis of [18F]Fluoromisonidazole and its use in PET
      imaging in an experimental model of subarachnoid hemorrhage.
AB  - Cerebral damage secondary to the vasospasm due to subarachnoid hemorrhage (SAH)
      is an important cause of morbid-mortality. We propose the use of the PET tracer
      [18F]Fluoromisonidazole to visualize the hypoxia due to the vasospasm. On the
      other hand [18F]Fluoromisonidazole synthesis process was optimized, avoiding HPLC
      purification using SPE cartridges instead, and reducing some synthesis steps.
      [18F]Fluoromisonidazole in vitro stability was tested for ten hours, and in vivo
      PET/CT images showed higher cerebral uptake in hemorrhagic animals than in
      control rats.

PMID- 29172059
TI  - Hydroxamate column-based purification of zirconium-89 (89Zr) using an automated
      fluidic platform.
AB  - Zirconium-89 (89Zr) is a long-lived (t1/2 = 78.4h) positron-emitting isotope that
      is useful for positron emission tomography (PET) based diagnostic imaging using
      radiolabeled antibodies. Hydroxamate resin columns are predominantly used for the
      purification of 89Zr from cyclotron bombarded natY targets dissolved in strong
      HCl. 89Zr is conventionally eluted from the resin in 1M oxalic acid (H2C2O4), a
      complexant that is conducive to follow-on binding of 89Zr through a
      transchelation process to the deferoxamine siderophore. In the present study, we
      determined that a lower concentration of H2C2O4 eluent (0.8M) is adequate to
      efficiently remove 89Zr from a column containing 100mg hydroxamate resin. As a
      result, less buffering agents are needed to be added to the 89Zr product fraction
      prior to labeling. A simple automated fluidic system prototype has been developed
      to perform the steps required for 89Zr purification using a hydroxamate resin
      column (column conditioning in HCl, Y target dissolution, dissolved target
      solution load onto column, column washes using HCl and water, and 89Zr elution).
      The system performance was evaluated using several cyclotron bombarded Y targets;
      89Zr product fractions demonstrated excellent chemical recoveries from these
      targets, with 1.0mL product volumes yielding 89+/-2% of the column elution peak
      activity and 84+/-2% of 89Zr recovered from the target (at EOB). These results
      compare favorably with previously published 89Zr product volumes and yields,
      despite the lower concentration of H2C2O4 eluent employed. Transchelation of
      resulting 89Zr product fractions was performed to assess product quality. The
      effective specific activity (ESA) ranged between 44(7) and 109(22) TBq.mmole-1,
      while the bindable metals concentration, a metric introduced for assessing and
      comparing product purity, ranged between 43(7) and 115(27) nmole.g-1.

PMID- 29172060
TI  - Thinness pressures in ethnically diverse college women in the United States.
AB  - While research consistently supports the negative impact of thinness pressures on
      body image, this work has primarily utilized White samples in the United States,
      limiting generalizability to other ethnicities. Further, limited research has
      examined ethnic differences in thinness pressures from distinct sociocultural
      influences. This study examined distinct sources of thinness pressures in 598
      White, 135 Black, and 131 Hispanic college women in the United States. Mean
      levels of thinness pressures significantly differed across ethnicity, with Black
      women generally reporting the lowest levels of each pressure. Additionally,
      distinct sources of thinness pressures were more highly related to negative
      outcomes within ethnic groups. For White women, each source was salient for
      disordered eating. For Black women, family pressure was particularly salient for
      appearance evaluation. For Hispanic women, family pressure was particularly
      salient for disordered eating and appearance evaluation. Findings suggest
      possible ethnic differences in the relative salience of some pressures over
      others.

PMID- 29172061
TI  - Self-objectification, body shame, and disordered eating: Testing a core
      mediational model of objectification theory among White, Black, and Hispanic
      women.
AB  - Objectification theory asserts that self-objectification, which manifests as self
      surveillance, leads to increased body shame and subsequent eating pathology.
      Although evidence supports the core mediational model, the majority of this work
      utilizes primarily White samples, limiting generalizability to other ethnic
      groups. The current study examined whether the core tenets of objectification
      theory generalize to Black and Hispanic women. Participants were 880 college
      women from the United States (71.7% White, 15.1% Hispanic, 13.2% Black) who
      completed self-report measures of self-surveillance, body shame, and disordered
      eating. Multivariate analysis of variance tests indicated lower levels of self
      surveillance and disordered eating among Black women. Moreover, body shame
      mediated the relationship between self-surveillance and disordered eating for
      White and Hispanic women, but not for Black women. These analyses support growing
      evidence for the role of body shame as a mediator between body surveillance and
      eating pathology, but only for women in certain ethnic groups.

PMID- 29172062
TI  - Association of nutrition and immune-endocrine dysfunction with muscle mass and
      performance in cognitively impaired older adults.
AB  - BACKGROUND: With lean mass declining early in Alzheimer's disease, muscle quality
      beyond quantity is relevant to physical performance. We sought to identify
      potentially modifiable factors for the differential loss of muscle mass (pre
      sarcopenia) and its performance (sarcopenia) in older adults with mild cognitive
      impairment (MCI) and mild-to-moderate Alzheimer's disease (AD). METHODS: This is
      a cross-sectional study of 108 community-dwelling older adults with MCI and mild
      to-moderate AD. Participants were categorized as: (i) No sarcopenia (normal
      muscle mass), (ii) Pre-sarcopenia (low muscle mass without weakness or slowness),
      (iii) Sarcopenia (low muscle mass AND weak grip strength and/or slow gait speed)
      using Asian cut-offs. Muscle quality was defined as the ratio of grip and knee
      extension strength to average arm and leg lean mass respectively. We measured
      cognitive, functional and physical (Short Physical Performance Battery, SPPB)
      performance; physical activity level; nutritional status; and blood biomarkers of
      inflammation and endocrine dysfunction. RESULTS: SPPB (p=0.033) and activity
      level (p=0.010) were highest in the pre-sarcopenic group. Pre-sarcopenic group
      had highest arm muscle quality [10.6 (7.7-12.2) vs 13.9 (12.6-15.7) vs 11.3 (9.7
      12.8), p<0.001], despite significantly lower appendicular lean mass than non
      sarcopenic group. In multi-nomial logistic regression reference to non-sarcopenic
      group, malnutrition independently increased risk for both pre-sarcopenia
      (Relative risk=7.53, 95% C.I 1.20-47.51, p=0.032) and sarcopenia (Relative
      risk=11.91, 95% C.I 2.85-49.77, p=0.001). A combined pro-inflammatory and
      endocrine deficient state significantly increased the risk of sarcopenia
      (Relative risk=5.17, 95% C.I 1.31-20.37, p=0.019). CONCLUSION: Malnutrition is a
      precursor for progressive loss of muscle mass, but a pro-inflammatory and
      endocrine deficient state may potentially aggravate decline in muscle quality to
      culminate in frank sarcopenia.

PMID- 29172063
TI  - Protective effect of catechin on humoral and cell mediated immunity in rat model.
AB  - The present study was focused on examining the effect of catechin on the cellular
      and humoral immunity in rat model. Immunomodulatory effect of catechin was
      determined by delayed-type hypersensitivity (DTH) response, carbon clearance
      assay, leucocyte mobilization test and cyclophosphamide-induced myelosuppression
      and hemagglutinating antibody (HA) titer assay. Catechin in experimental dose
      (25, 50 and 100mg/kg, p.o.) elevated a significant increase in antibody titer in
      the hemagglutination test with increased levels of immunoglobulin. There was an
      enhancement in the delayed-type hypersensitivity reaction produced by sheep red
      blood cells. There was also restoration in the functioning of leucocytes in
      cyclophosphamide-treated rats with an increased clearance of carbon particles.
      The results of the present study signify that catechin possesses sufficient
      potential for modulating immune activity by cellular and humoral mechanisms.

PMID- 29172064
TI  - Propofol attenuates myocardial ischemia reperfusion injury partly through
      inhibition of resident cardiac mast cell activation.
AB  - Cardiac mast cell activation is involved in the process of myocardial ischemia
      reperfusion (I/R) injury and exacerbates myocardial infarction. Propofol, an
      anesthetic with antioxidant property, can reduce myocardial infarct size in I/R
      injury. The present study was designed to investigate whether propofol can
      attenuate myocardial I/R injury by inhibiting resident cardiac mast cell
      activation by a Langendorff model. Thirty rats were randomly assigned to 5 groups
      (n=6 per group): control group and four test groups (I/R, I/R+compound 48/80,
      I/R+propofol, I/R+compound 48/80+propofol). Cultured RBL-2H3 cells were
      pretreated with propofol and subjected to mast cell degranulator compound48/80
      (C48/80).Microscopically, degradation of myofibrillar and degranulation of mast
      cells were studied using hematoxylin-eosin toluidine blue staining techniques.
      After the effluent was assayed for tryptase, LDH, CK-MB and cTnI, myocardial
      tissue was evaluated for cytokine levels and infarct area. Heart subjected to I/R
      showed significantly increased expression of cytokines (TNF-alpha and IL-6), LDH,
      CK-MB and cTnI. In addition, the I/R-induced heart also showed greater
      histopathological injury and a larger infarction zone, following increased mast
      cell degranulation with concomitant rise in tryptase. Mast cell degranulation by
      C48/80 further aggravated I/R injury. However, all of these effects were
      suppressed by propofol pretreatment, which also abrogated C48/80-mediated
      exacerbation of I/R injury. Also, propofol attenuated the C48/80-evoked tryptase
      and histamine release in RBL-2H3 cells. It is concluded that pretreatment of
      propofol confers protection against I/R injury partly by inhibiting resident
      cardiac mast cell activation.

PMID- 29172065
TI  - DNA methylation markers in combination with skeletal and dental ages to improve
      age estimation in children.
AB  - Age estimation is critical in forensic science, in competitive sports and games
      and in other age-related fields, but the current methods are suboptimal. The
      combination of age-associated DNA methylation markers with skeletal age (SA) and
      dental age (DA) may improve the accuracy and precision of age estimation, but no
      study has examined this topic. In the current study, we measured SA (GP, TW3-RUS,
      and TW3-Carpal methods) and DA (Demirjian and Willems methods) by X-ray
      examination in 124 Chinese children (78 boys and 46 girls) aged 6-15 years. To
      identify age-associated CpG sites, we analyzed methylome-wide DNA methylation
      profiling by using the Illumina HumanMethylation450 BeadChip system in 48
      randomly selected children. Five CpG sites were identified as associated with
      chronologic age (CA), with an absolute value of Pearson's correlation coefficient
      (r)>0.5 (p<0.01) and a false discovery rate<0.01. The validation of age
      associated CpG sites was performed using droplet digital PCR techniques in all
      124 children. After validation, four CpG sites for boys and five CpG sites for
      girls were further adopted to build the age estimation model with SA and DA using
      multivariate linear stepwise regressions. These CpG sites were located at 4 known
      genes: DDO, PRPH2, DHX8, and ITGA2B and at one unknown gene with the Illumina ID
      number of 22398226. The accuracy of age estimation methods was compared according
      to the mean absolute error (MAE) and root mean square error (RMSE). The best
      single measure for SA was the TW3-RUS method (MAE=0.69years, RMSE=0.95years) in
      boys, and the GP method (MAE=0.74years, RMSE=0.94years) in girls. For DA, the
      Willems method was the best single measure for both boys (MAE=0.63years,
      RMSE=0.78years) and girls (MAE=0.54years, RMSE=0.68years). The models that
      incorporated SA and DA with the methylation levels of age-associated CpG sites
      provided the highest accuracy of age estimation in both boys (MAE=0.47years,
      R2=0.886) and girls (MAE=0.33years, R2=0.941). Cross validation of the results
      confirmed the reliability and validity of the models. In conclusion, age
      associated DNA methylation markers in combination with SA and DA greatly improve
      the accuracy of age estimation in Chinese children. This method may be applied in
      forensic science, in competitive sports and games and in other age-related
      fields.

PMID- 29172066
TI  - Discrimination of relationships with the same degree of kinship using chromosomal
      sharing patterns estimated from high-density SNPs.
AB  - Distinguishing relationships with the same degree of kinship (e.g., uncle-nephew
      and grandfather-grandson) is generally difficult in forensic genetics by using
      the commonly employed short tandem repeat loci. In this study, we developed a new
      method for discerning such relationships between two individuals by examining the
      number of chromosomal shared segments estimated from high-density single
      nucleotide polymorphisms (SNPs). We computationally generated second-degree
      kinships (i.e., uncle-nephew and grandfather-grandson) and third-degree kinships
      (i.e., first cousins and great-grandfather-great-grandson) for 174,254 autosomal
      SNPs considering the effect of linkage disequilibrium and recombination for each
      SNP. We investigated shared chromosomal segments between two individuals that
      were estimated based on identity by state regions. We then counted the number of
      segments in each pair. Based on our results, the number of shared chromosomal
      segments in collateral relationships was larger than that in lineal relationships
      with both the second-degree and third-degree kinships. This was probably caused
      by differences involving chromosomal transitions and recombination between
      relationships. As we probabilistically evaluated the relationships between
      simulated pairs based on the number of shared segments using logistic regression,
      we could determine accurate relationships in >90% of second-degree relatives and
      >70% of third-degree relatives, using a probability criterion for the
      relationship >=0.9. Furthermore, we could judge the true relationships of actual
      sample pairs from volunteers, as well as simulated data. Therefore, this method
      can be useful for discerning relationships between two individuals with the same
      degree of kinship.

PMID- 29172067
TI  - Improving communication at handover and transfer reduces retained swabs in
      maternity services.
AB  - OBJECTIVE: To reduce the incidence of retained vaginal swabs and near misses.
      STUDY DESIGN: A review of previous retained swab incidents and near misses in a
      large maternity unit identified handovers and transfers as a key point of
      vulnerability. Interventions were introduced to improve communication at handover
      from the delivery suite to theatre and from theatre to the high dependency unit.
      Process data was collected to monitor compliance. The outcome measures were the
      incidence of retained swab never events and the incidence of near misses. Chi
      squared analysis was used to test the significance of the results. RESULTS: For
      transfers from delivery suite to theatre, verbal handover significantly increased
      from 28.8% to 75.6% (p<0.0001), and written handover significantly increased from
      4.4% to 62.9% (p<0.0001). There were 291 transfers to theatre post-intervention:
      in 88 (30.2%) of these transfers a vaginal swab was already in situ. In 70/88
      (79.5%) of cases the presence of the swab was communicated to theatre staff in
      three ways (verbally, written and transfer of opened swab packets) according to
      the new policy. In the post-intervention period there were 56 women transferred
      from theatre to the high-dependency unit with a vaginal pack in situ: 52 (92.9%)
      of these women had a sticker in place serving as a constant reminder of the
      presence of the vaginal pack to staff. Following a baseline of four near misses
      in two months, there has been only one near miss in the 15 months since the
      interventions were implemented, (33.3% vs. 1.1%, p<0.0001). There have been no
      retained swab incidents since the project commenced. CONCLUSIONS: Simple
      interventions to improve communication at handover and transfer can reduce the
      incidence of retained vaginal swabs and near misses. Further work is needed to
      raise the profile of swab counting in maternity settings: swab counting needs to
      be the responsibility of all disciplines, not just the responsibility of theatre
      staff.

PMID- 29172068
TI  - Gestational diabetes-Predictors of response to treatment and obstetric outcome.
AB  - OBJECTIVE: Evaluate patient characteristics that are predictors of treatment
      response and outcomes in gestational diabetes STUDY DESIGN: Retrospective cohort
      of 265 women with gestational diabetes treated with diet/metformin and/or insulin
      in a single centre over 2 years. RESULTS: Multinomial logistic regression showed
      that (after adjusting for age and ethnicity) women who were of normal weight were
      more likely to be on diet and women who were obese were more likely to be on
      metformin or metformin and insulin(p=0.014). Women who were obese were twice more
      likely to have labour induced than those with normal weight. Onset of labour was
      the only parameter significantly associated with a treatment modality among the
      three groups (p<0.001). There was no difference in the incidence of large for
      gestational age, neonatal admission, shoulder dystocia or still birth between the
      three groups. CONCLUSIONS: Maternal BMI appears to be the only parameter that is
      predictive of need for treatment with metformin/insulin and the modality of
      treatment does not have an effect on maternal and neonatal outcomes.

PMID- 29172069
TI  - Antimutagenic action of the live yeast can be transmitted to the offspring of
      Drosophila melanogaster. A genetic study using the wing spot assay.
AB  - The present study evaluates whether the protective effect of live yeast (LY)
      against direct and indirect mutagenic agents, persists in the offspring from
      individuals fed with LY. The wing-spot test in Drosophila was used; four
      different mates were performed: a) neither females nor males were fed with LY
      enriched food (NLYxNLY); b) only females were fed (LYxNLY); c) males were fed
      (NLYxLY) or d) both progenitors were fed (LYxLY). Results confirm that LY
      strongly stimulates fecundity in females but not in males and provides strength
      to the egg for survive. A greater reduction in mutation rate was observed when
      females were feed, in the following relationship: LYxNLY>LYxLY>NLYxLY. No
      protection was found against action in any of the promutagens tested. Results
      suggest that LY has a very powerful antimutagenic action, predominantly against
      the action of ionizing radiation and Chromium trioxide that can be transmitted
      mainly through the female.

PMID- 29172070
TI  - Vertical transmission of positive-sense single-stranded RNA viruses in plants as
      a model for arboviral induced teratogenesis.
AB  - Teratogenic viruses have increased public health importance with the emergence of
      Zika virus and a recent decline in rubella virus vaccination. Of the seven
      viruses known to cause birth defects in humans, three are mosquito-borne
      pathogens. Ethical oversight, compliance, rising costs, and the need for
      specialized training slow the pace of study of these human pathogens compared to
      study of similar teratogenic viruses in plants. Plant viruses have served as
      models for human viruses which can be applied to animal systems. This review
      describes the similar features of plant and animal teratogenic arboviruses and
      the common systems and barriers that are encountered during vertical transmission
      in the host.

PMID- 29172072
TI  - Reproductive effects of arteriviruses: equine arteritis virus and porcine
      reproductive and respiratory syndrome virus infections.
AB  - Equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome
      virus (PRRSV) are the most economically important members of the family
      Arteriviridae. EAV and PRRSV cause reproductive and respiratory disease in equids
      and swine, respectively and constitute a significant economic burden to equine
      and swine industries around the world. Furthermore, they both cause abortion in
      pregnant animals and establish persistent infection in their natural hosts, which
      fosters viral shedding in semen leading to sexual transmission. The primary focus
      of this article is to provide an update on the effects of these two viruses on
      the reproductive tract of their natural hosts and provide a comparative analysis
      of clinical signs, virus-host interactions, mechanisms of viral pathogenesis and
      viral persistence.

PMID- 29172071
TI  - Zika virus infection of first-trimester human placentas: utility of an explant
      model of replication to evaluate correlates of immune protection ex vivo.
AB  - The emergence of congenital Zika virus (ZIKV) disease, with its devastating
      effects on the fetus, has prompted development of vaccines and examination of how
      ZIKV breaches the maternal-fetal barrier. Infection of placental and decidual
      tissue explants has demonstrated cell types at the uterine-placental interface
      susceptible to infection and suggests routes for transmission across the placenta
      and amniochorionic membrane. ZIKV replicates in proliferating Hofbauer cells
      within chorionic villi in placentas from severe congenital infection. Explants of
      anchoring villi recapitulate placental architecture and early-stage development
      and suggest infected Hofbauer cells disseminate virus to fetal blood vessels.
      ZIKV infection of explants represents a surrogate human model for evaluating
      protection against transmission by antibodies in vaccine recipients and passive
      immune formulations and novel therapeutics.

PMID- 29172073
TI  - Intrinsic sodium currents and excitatory synaptic transmission influence
      spontaneous firing in up and down activities.
AB  - Periodic up and down transitions of membrane potentials are considered to be a
      significant spontaneous activity. These kinds of oscillations always accompany
      with some spontaneous firing in up state. Our previous theoretical studies mainly
      looked at the subthreshold up and down transitions and characteristics of up and
      down dynamics. In this paper, we focus on suprathreshold spontaneous firing of up
      and down transitions based on improved network model and its stimulations. The
      simulated results indicate that fast sodium current is critical to the generation
      of spontaneous neural firing. While persistent sodium current plays a part in
      spontaneous fluctuation. Both intrinsic fast and persistent sodium dynamics
      influence spontaneous firing rate and synchronous activity in up and down
      behavior. Meanwhile, blocking excitatory synaptic transmission decreases neural
      firing and reveals spontaneous firing. These simulated results are basically in
      accordance with experimental results. Through the observation and analysis of the
      findings, we prove the validity of the model so we can further adopt this model
      to study other properties and characteristics of the network, laying the
      foundation for further work on cortex activity.

PMID- 29172074
TI  - Using rotated speech to approximate the acoustic mismatch negativity response to
      speech.
AB  - The mismatch negativity (MMN) response is influenced by the magnitude of the
      acoustic difference between standard and deviant, and the response is typically
      larger to linguistically relevant changes than to linguistically irrelevant
      changes. Linguistically relevant changes between standard and deviant typically
      co-occur with differences between the two acoustic signals. It is therefore not
      straightforward to determine the contribution of each of those two factors to the
      MMN response. This study investigated whether spectrally rotated speech can be
      used to determine the impact of the acoustic difference on the MMN response to a
      combined linguistic and acoustic change between standard and deviant. Changes
      between rotated vowels elicited an MMN of comparable amplitude to the one
      elicited by a within-category vowel change, whereas the between-category vowel
      change resulted in an MMN amplitude of greater magnitude. A change between
      rotated vowels resulted in an MMN ampltude more similar to that of a within-vowel
      change than a complex tone change did. This suggests that the MMN amplitude
      reflecting the acoustic difference between two speech sounds can be well
      approximated by the MMN amplitude elicited in response to their rotated
      counterparts, in turn making it possible to estimate the part of the response
      specific to the linguistic difference.

PMID- 29172075
TI  - Real-time RT-PCR for Mayaro virus detection in plasma and urine.
AB  - BACKGROUND: Mayaro virus (MAYV) causes an acute febrile illness which can be
      difficult to differentiate from dengue or chikungunya. MAYV RNA can be detected
      in plasma during the first 3-5days of illness, but only a single rRT-PCR has been
      fully evaluated in the literature. OBJECTIVES: To develop an rRT-PCR for MAYV and
      evaluate assay performance using human plasma and urine samples spiked with
      different MAYV strains. STUDY DESIGN: A MAYV rRT-PCR targeting a region of the
      5'UTR and nsp1 gene was designed from the alignment of all complete-genome MAYV
      sequences to be compatible with existing laboratory protocols. The assay was
      evaluated using human samples spiked with six MAYV strains, including strains
      from each of the three genotypes. RESULTS: The linear range of the MAYV rRT-PCR
      extended from 1.0 to 8.0 log10copies/MUL, and the lower limit of 95% detection
      was 8.2copies/MUL. No detection was observed when the MAYV rRT-PCR was tested
      with genomic RNA from related arboviruses. The assay demonstrated linear
      amplification of all 6 MAYV strains when spiked into human plasma samples as well
      as 2 strains spiked into urine. CONCLUSIONS: We report the design and evaluation
      of an rRT-PCR for MAYV. Given the concern for MAYV emergence in the Americas and
      the few molecular tests that have been evaluated in the literature, this assay
      should provide a useful diagnostic for patients with an acute febrile illness.

PMID- 29172076
TI  - Gemtuzumab Ozogamicin (GO) Inclusion to Induction Chemotherapy Eliminates
      Leukemic Initiating Cells and Significantly Improves Survival in Mouse Models of
      Acute Myeloid Leukemia.
AB  - Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate for the
      treatment of acute myeloid leukemia (AML). Although GO shows a narrow therapeutic
      window in early clinical studies, recent reports detailing a modified dosing
      regimen of GO can be safely combined with induction chemotherapy, and the
      combination provides significant survival benefits in AML patients. Here we
      tested whether the survival benefits seen with the combination arise from the
      enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs).
      Herein, we use cell line and patient-derived xenograft (PDX) AML models to
      evaluate the combination of GO with daunorubicin and cytarabine (DA) induction
      chemotherapy on AML blast growth and animal survival. DA chemotherapy and GO as
      separate treatments reduced AML burden but left significant chemoresidual disease
      in multiple AML models. The combination of GO and DA chemotherapy eliminated
      nearly all AML burden and extended overall survival. In two small subsets of AML
      models, chemoresidual disease following DA chemotherapy displayed hallmark
      markers of leukemic LICs (CLL1 and CD34). In vivo, the two chemoresistant
      subpopulations (CLL1+/CD117- and CD34+/CD38+) showed higher ability to self
      renewal than their counterpart subpopulations, respectively. CD33 was coexpressed
      in these functional LIC subpopulations. We demonstrate that the GO and DA
      induction chemotherapy combination more effectively eliminates LICs in AML PDX
      models than either single agent alone. These data suggest that the survival
      benefit seen by the combination of GO and induction chemotherapy, nonclinically
      and clinically, may be attributed to the enhanced reduction of LICs.

PMID- 29172077
TI  - Photoresponsive azo-combretastatin A-4 analogues.
AB  - Colchicine analogues in which an azo group is incorporated into a molecule
      containing the key pharmacophore of colchicine, have found particular utility as
      switchable tubulin binding chemotherapeutics. Combretastatin is a related
      compound containing a stilbene fragment that shows different bioactivity for the
      cis and trans isomers. We have performed cell assays on 17 new compounds
      structurally related to a previously reported azo-analogue of combretastatin. One
      of these compounds showed enhanced potency against HeLa (IC50 = 0.11 MUM) and
      H157 cells (IC50 = 0.20 MUM) for cell studies under 400 nm irradiation and the
      highest photoactivity (IC50 with irradiation/IC50 in dark = 550). We have
      performed docking and physicochemical studies of this new compound (7). Kinetic
      studies in water reveal a longer half-life for the cis isomer of 7 which may be
      one factor responsible for the better IC50 values in cell assays and the improved
      photoresponsive behavior.

PMID- 29172078
TI  - Synthesis and biological evaluation of a novel beta-D-2'-deoxy-2'-alpha-fluoro-2'
      beta-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of
      hepatitis C virus infection.
AB  - A novel beta-D-2'-deoxy-2'-alpha-fluoro-2'-beta-C-(fluoromethyl)uridine
      phosphoramidate prodrug (1) has been synthesized. This compound exhibits
      submicromolar-level antiviral activity in vitro against HCV genotypes 1b, 1a, 2a,
      and S282T replicons (EC50 = 0.18-1.13 MUM) with low cytotoxicity (CC50 > 1000
      MUM). Administered orally, prodrug 1 is well tolerated at doses of up to 4 g/kg
      in mice, and produces a high level of the corresponding triphosphate in rat
      liver.

PMID- 29172079
TI  - Design, syntheses and lipid accumulation inhibitory activities of novel
      resveratrol mimics.
AB  - Hispidine was initially discovered from Ficus Hispida for cardiovascular
      protection. In this paper, hispidine derivatives, which contain a novel
      resveratrol-like scaffold, have been designed, synthesized, and assayed as agents
      against lipid accumulations in 3T3-L1 pre-adipocytes. Six hispidine derivatives
      have the activity of reducing TG in 3T3-L1 adipocytes in dosage-dependent manner.
      The most active compound can reduce the lipid accumulation up to 78.4% at 10 MUM
      qPCR and Western blotting results demonstrate that the two most active compounds
      inhibit both lipodenesis and adipogenesis in 3T3-L1 cells through (1) increasing
      the phosphorylations of AMPK and ACC, promoting SIRT1 expression. These three
      proteins are key regulators for lipogenesis and energy metabolism. (2) Decreasing
      the expressions of PPARgamma, sREBP-1c, and FABP4, which are pivotal regulators
      for adipogenesis. Overall, this work proves that hispidine derivatives diminish
      the lipid accumulation in 3T3-L1 cell line by downregulating lipogenic and
      adipogenic pathways.

PMID- 29172080
TI  - Synthesis of unprecedented steroidal spiro heterocycles as potential
      antiproliferative drugs.
AB  - Herein we report the straightforward preparation of novel conformationally
      restricted steroids from trans-androsterone and estrone, decorated with spiranic
      oxazolidin-2-one or 2-aminooxazoline motifs at C-17 as potential
      antiproliferative agents. Such unprecedented pharmacophores were accessed using
      an aminomethylalcohol derivative at C-17 as the key intermediate; reaction of
      such functionality with triphosgene, or conversion into N-substituted thioureas,
      followed by an intramolecular cyclodesulfurization reaction promoted by yellow
      HgO, furnished such spirocycles in excellent yields. Title compounds were tested
      in vitro against a panel of six human tumor cell lines, named A549 (non-small
      cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D
      (breast) and WiDr (colon), and the results were compared with steroidal
      chemotherapeutic agents (abiraterone and galeterone); the A-ring of the steroidal
      backbone, the nature of the heterocycle and the N-substituents proved to be
      essential motifs for establishing structure-activity relationships concerning not
      only the potency but also the selectivity against tumor cell lines. Estrone
      derivatives, particularly those bearing a spiranic 2-aminooxazoline scaffold were
      found to be the most active compounds, with GI50 values ranging from the low
      micromolar to the submicromolar level (0.34-1.5 MUM). Noteworthy, the lead
      compounds showed a remarkable increase in activity against the resistant cancer
      cell lines (T-47D and WiDr) compared to the anticancer reference drugs (up to 120
      fold).

PMID- 29172081
TI  - Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted
      pyrimidinylthiourea derivatives as multifunctional agents for the treatment of
      Alzheimer's disease.
AB  - A series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-3)
      were designed and synthesized as multifunctional agents for Alzheimer's disease
      (AD) therapy, and their potential was evaluated through various biological
      experiments. Among these derivatives, compound 1b displayed good selective
      inhibitory activity against AChE (vs BuChE, IC50 = 0.324 MUM, SI > 123) and MAO-B
      (vs MAO-A, IC50 = 1.427 MUM, SI > 35). Molecular docking study showed that the
      pyrimidinylthiourea moiety of 1b could bind to the catalytic active site (CAS) of
      AChE, and the propargylamine moiety interacted directly with the flavin adenine
      dinucleotide (FAD) of MAO-B. Moreover, 1b demonstrated mild antioxidant ability,
      good copper chelating property, effective inhibitory activity against Cu2+
      induced Abeta1-42 aggregation, moderate neuroprotection, low cytotoxicity, and
      appropriate blood-brain barrier (BBB) permeability in vitro and was capable of
      ameliorating scopolamine-induced cognitive impairment in mice. These results
      indicated that 1b has the potential to be a multifunctional candidate for the
      treatment of Alzheimer's disease.

PMID- 29172082
TI  - Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2
      thione derivatives as tumor cell specific pyruvate kinase M2 activators.
AB  - Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic
      glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in
      cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione
      compound 2 as a novel PKM2 activator from a random screening of an in-house
      compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione
      derivatives were designed and synthesized for screening as potent PKM2
      activators. Among these, some compounds showed higher PKM2 activation activity
      than lead compound 2 and also exhibited significant anti-proliferative activities
      on human cancer cell lines at nanomolar concentration. The compound 5w was
      identified as the most potent antitumor agent, which showed excellent anti
      proliferative effects with IC50 values from 0.46 MUM to 0.81 MUM against H1299,
      HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor
      cell line HELF compared with cancer cells. In addition, Preliminary
      pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase
      in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized
      through docking studies.

PMID- 29172083
TI  - Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents:
      Design, synthesis and biological evaluation.
AB  - A series of novel aminopyrimidinyl benzimidazoles as potentially antimicrobial
      agents were designed, synthesized and characterized by IR, NMR and HRMS spectra.
      The biological evaluation in vitro revealed that some of the target compounds
      exerted good antibacterial and antifungal activity in comparison with the
      reference drugs. Noticeably, compound 7d could effectively inhibit the growth of
      A. flavus, E. coli DH52 and MRSA with MIC values of 1, 1 and 8 MUg/mL,
      respectively. Further studies revealed that pyrimidine derivative 7d could
      exhibit bactericidal mode of action against both Gram positive (S. aureus and
      MRSA) and Gram negative (P. aeruginosa) bacteria. The active molecule 7d showed
      low cell toxicity and did not obviously trigger the development of resistance in
      bacteria even after 16 passages. Furthermore, compound 7d was able to
      beneficially regulate reactive oxygen species (ROS) generation for an excellent
      safety profile. Molecular docking study revealed that compound 7d could bind with
      DNA gyrase by the formation of hydrogen bonds. The preliminary exploration for
      antimicrobial mechanism disclosed that compound 7d could effectively intercalate
      into calf thymus DNA to form a steady supramolecular complex, which might further
      block DNA replication to exert the powerful bioactivities. The binding
      investigation of compound 7d with human serum albumins (HSA) revealed that this
      molecule could be effectively transported by HSA.

PMID- 29172084
TI  - Synthesis and biological evaluation of N-substituted 3-oxo-1,2,3,4-tetrahydro
      quinoxaline-6-carboxylic acid derivatives as tubulin polymerization inhibitors.
AB  - A series of novel N-substituted 3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxy-
      lic acid derivatives were synthesized and evaluated for their biological
      activities. Among all synthesized target compounds, 13d exhibited the most potent
      antiproliferative activity against HeLa, SMMC-7721, K562 cell line (IC50 = 0.126
      MUM, 0.071 MUM, 0.164 MUM, respectively). Furthermore, compound 13d inhibited
      tubulin polymerization (IC50 = 3.97 MUM), arrested cell cycle at the G2/M phase
      and induced apoptosis. The binding mode at the colchicine binding site was also
      probed. These studies provided a new molecular scaffold for the further
      development of antitumor agents that target tubulin.

PMID- 29172085
TI  - Design, synthesis and pharmacological evaluation of N-(5-chloro-2,4
      dihydroxybenzoyl)-(R)-N-arylmethyl-1,2,3,4-tetrahydro-3-isoquinolinecarboxamides
      as potent Hsp90 inhibitors.
AB  - Using diverse arylmethyl groups to replace the benzyl moiety of the lead Hsp90
      inhibitor 1 (N-(5-chloro-2,4-dihydroxybenzoyl)-(R)-N-benzyl-1,2,3,4-tetrahydro-3
      iso quinolinecarboxamide), thirty four derivatives (10-43) were developed, and
      exhibited improved Hsp90 inhibitory and antiproliferative activities. SAR
      analysis indicated that the southeastern aryl substitutions influenced their
      antiproliferative activities obviously, with the para-pyridyl group (41)
      outperforming all other substitution patterns. In this regard, compound 41 was
      selected for further evaluation. CETSA melt and ITDRFCETSA (isothermal dose
      response fingerprint) curves for Hsp90alpha further proved that 41 interacted
      with intracellular Hsp90alpha powerfully. Compared with the lead compound 1,
      docking and MD refinement of the Hsp90alpha-41 complex revealed a favorable H
      bonding interaction between the side-chain of Tyr139 and the pyridine moiety of
      41, which is the first time to be used for resorcinol-based Hsp90 inhibitors.
      With broad-spectral antitumor activity, compound 41 induced time- and dose
      dependent growth inhibition and G0/G1 cell cycle arrest on human breast cancer
      MDA-MB-453 cell line. In addition, flow cytometry and Western blot analyses
      confirmed that 41 induced apoptosis of human breast cancer MDA-MB-453 cell line.
      Via degradation of IKKs and suppression of IKKs activity, compound 41 inhibited
      TNF-alpha-induced NF-kappaB activation. The overall properties warrant compound
      41 a promising Hsp90 inhibitor and further biological characterizations. This
      study provides insights into the chemical evolution of Hsp90 inhibitors, and may
      facilitate the design of next generation Hsp90 inhibitors for the antitumor drug
      development.

PMID- 29172087
TI  - Development of a group work assessment pedagogy using constructive alignment
      theory.
AB  - The purpose of this paper is to explore group work assessment underpinned by
      constructive alignment theory to develop a new assessment pedagogy. A review was
      undertaken of an existing module 'Mental Health Nursing 1', with student nurses
      participating in the BSc (Hons) Nursing Programme. Constructive alignment theory
      requires teachers to adopt a deep approach to learning where module learning
      outcomes are aligned with the teaching environment and modes of assessment. As
      the module progressed, reviewing the Mental Health Nursing 1 module became an
      excellent opportunity to begin to understand how constructive alignment theory
      can inform a group work assessment pedagogy. Working using a constructively
      aligned assessment process became a valuable learning experience for the module
      leader whilst at the same time revealed a gap in the research around the impact
      of constructively aligned teaching and group work assessment.

PMID- 29172086
TI  - Synthesis of new 1-benzyl tetrahydropyridinylidene ammonium salts and their
      antimicrobial and anticellular activities.
AB  - A series of N-benzyl tetrahydropiperidinylidene pyrrolidinium salts have been
      synthesized and investigated for their antiplasmodial and antitrypanosomal
      activities as well as for their cytotoxic effects. The antibacterial,
      antimycobacterial and anticancer potencies of selected compounds were examined,
      too. Physicochemical parameters were calculated and structure-activity
      relationships are discussed.

PMID- 29172088
TI  - Silencing of H19 inhibits the adipogenesis and inflammation response in ox-LDL
      treated Raw264.7 cells by up-regulating miR-130b.
AB  - Atherosclerosis (AS) is the main cause of cardiovascular diseases (CADs). Lipid
      accumulation and inflammatory response in macrophages are two key factors in the
      pathogenesis of AS. In this study, we aimed to explore the regulating role of
      long non-coding RNA (LncRNA)-H19 in oxygenized low density lipoprotein (ox-LDL)
      treated Raw264.7 cells. Compared with the healthy control, a relatively higher
      level of H19 was detected in the blood samples from AS patients. Obviously up
      regulated expression of TG (triglycerides)/TC (total cholesterol)/LDL-C (low
      density lipoprotein-cholesterol) and down-regulated level of HDL-C (high density
      lipoprotein-cholesterol) were detected in ox-LDL-treated Raw264.7 cells. Besides
      that, increased expression of H19 was detected in ox-LDL-treated Raw264.7 cells.
      To examine the function of H19, gene knockdown was performed using short hairpin
      RNAs (shRNAs). The expression of TG, TC, LDL-C and HDL-C was detected by enzyme
      linked immunosorbent assay (Elisa) and the expression of lipolytic
      genes/lipogenic genes (PPARalpha, CPT-1/REBP-1c, ACS) was examined through
      western blot. In combination with the result of oil red O staining, we concluded
      that H19 shRNA effectively decreased lipid accumulation in ox-LDL-treated
      Raw264.7 cells. Besides that, H19 shRNA decreased the level of pro-inflammatory
      factors (TNF-alpha, IL-1beta)/CD68+ cells and increased the level of anti
      inflammatory factors (IL-4, IL-10)/CD163+ cells compared with the control group.
      Combined the bioinformatics analyses/luciferase assay with the promoting effect
      of H19 shRNA on the expression of miR-130b, we speculated that miR-130b was a
      target of H19 in ox-LDL-treated Raw264.7 cells. Moreover, the adding of LncRNA
      H19 abolished the facilitating effect of miR-130b inhibitor on adipogenesis and
      inflammation response by up-regulating the expression of miR-130b. Taken
      together, our research indicated a H19-miR130b pathway in regulating lipid
      metabolism and inflammation response in ox-LDL-treated Raw264.7 cells, providing
      new targets for AS treatment.

PMID- 29172089
TI  - Retargeted and detargeted adenovirus for gene delivery to the muscle.
AB  - We previously selected muscle binding peptides 12.51 and 12.52 from "context
      specific" phage display libraries for introduction into adenovirus (Ad) vectors.
      In this work, these peptides were inserted into the hypervariable region (HVR) 5
      loop of the Ad5 hexon protein to display 720 peptides per virions. HVR-12.51 and
      12.52 increased transduction of C2C12 cells up to 20-fold when compared to
      unmodified Ad5. 12.51 increased in vivo muscle transduction 2 to 7-fold over
      unmodified Ad after intramuscular injection in mice and hamsters. 12.52 did not
      increase muscle transduction. Notably, insertion of 12.51 into the hexon reduced
      liver transduction 80-fold when compared to unmodified Ad5 after intravenous
      injection. Increased muscle transduction in mice translated into increased immune
      responses after gene-based vaccination. These data suggest there are merits to
      retargeting and detargeting benefits to modifying the hexons of Ads with peptide
      ligands.

PMID- 29172091
TI  - Neural mechanisms of movement planning: motor cortex and beyond.
AB  - Neurons in motor cortex and connected brain regions fire in anticipation of
      specific movements, long before movement occurs. This neural activity reflects
      internal processes by which the brain plans and executes volitional movements.
      The study of motor planning offers an opportunity to understand how the structure
      and dynamics of neural circuits support persistent internal states and how these
      states influence behavior. Recent advances in large-scale neural recordings are
      beginning to decipher the relationship of the dynamics of populations of neurons
      during motor planning and movements. New behavioral tasks in rodents, together
      with quantified perturbations, link dynamics in specific nodes of neural circuits
      to behavior. These studies reveal a neural network distributed across multiple
      brain regions that collectively supports motor planning. We review recent
      advances and highlight areas where further work is needed to achieve a deeper
      understanding of the mechanisms underlying motor planning and related cognitive
      processes.

PMID- 29172090
TI  - Nutritional status and diet as predictors of children's lead concentrations in
      blood and urine.
AB  - Lead exposure remains an important public health problem. Contaminated foods may
      act as a source of lead exposure, while certain nutrients may reduce lead
      absorption. We examined the cross-sectional associations of dietary patterns and
      the intake of several nutrients and foods with blood (Pb-B) and urinary (Pb-U)
      lead concentrations in children (5-8y) from Montevideo, Uruguay. From two 24-hour
      recalls completed by caregivers, we derived the mean daily intake of select
      nutrients and food groups (dairy, milk, fruit, root vegetables, foods rich in
      heme and non-heme iron), as well as "nutrient dense" and "processed" food
      patterns. Pb-B (n=315) was measured using atomic absorption spectrometry; Pb-U
      (n=321) using ICP-MS. Pb-U was adjusted for specific gravity and log-transformed
      to approximate a normal distribution. Iron deficiency (ID) and dietary variables
      were tested as predictors of Pb-B and log-Pb-U in covariate-adjusted regressions.
      Median [5%, 95%] Pb-B and Pb-U were 3.8 [0.8-7.8] MUg/dL and 1.9 [0.6-5.1] MUg/L,
      respectively; ~25% of Pb-B above current U.S. CDC reference concentration of
      5MUg/dL. ID was associated with 0.75MUg/dL higher Pb-B, compared to non-ID
      (p<0.05). Consumption of root vegetables was not associated with Pb-B or log-Pb
      U. Higher scores on the nutrient-dense pattern were related with higher Pb-Bs,
      possibly due to consumption of green leafy vegetables. Dietary intake of iron or
      iron-rich foods was not associated with biomarkers of lead. Conversely, children
      consuming more calcium, dairy, milk and yogurt had lower Pb-B and log-Pb-U. Our
      findings appear consistent with existing recommendations on including calcium
      rich, but not iron- or vitamin-C-rich foods in the diets of lead-exposed
      children, especially where the consumption of these foods is low.

PMID- 29172092
TI  - Visual field defects after temporal lobe resection for epilepsy.
AB  - PURPOSE: To determine visual field defects (VFDs) using methods of varying
      complexity and compare results with subjective symptoms in a population of newly
      operated temporal lobe epilepsy patients. METHODS: Forty patients were included
      in the study. Two patients failed to perform VFD testing. Humphrey Field Analyzer
      (HFA) perimetry was used as the gold standard test to detect VFDs. All patients
      performed a web-based visual field test called Damato Multifixation Campimetry
      Online (DMCO). A bedside confrontation visual field examination ad modum Donders
      was extracted from the medical records in 27/38 patients. All participants had a
      consultation by an ophthalmologist. A questionnaire described the subjective
      complaints. REULTS: A VFD in the upper quadrant was demonstrated with HFA in 29
      (76%) of the 38 patients after surgery. In 27 patients tested ad modum Donders,
      the sensitivity of detecting a VFD was 13%. Eight patients (21%) had a severe VFD
      similar to a quadrant anopia, thus, questioning their permission to drive a car.
      In this group of patients, a VFD was demonstrated in one of five
      (sensitivity=20%) ad modum Donders and in seven of eight (sensitivity=88%) with
      DMCO. Subjective symptoms were only reported by 28% of the patients with a VFD
      and in two of eight (sensitivity=25%) with a severe VFD. Most patients (86%)
      considered VFD information mandatory. CONCLUSION: VFD continue to be a frequent
      adverse event after epilepsy surgery in the medial temporal lobe and may affect
      the permission to drive a car in at least one in five patients. Subjective
      symptoms and bedside visual field testing ad modum Donders are not sensitive to
      detect even a severe VFD. Newly developed web-based visual field test methods
      appear sensitive to detect a severe VFD but perimetry remains the golden standard
      for determining if visual standards for driving is fulfilled. Patients consider
      VFD information as mandatory.

PMID- 29172094
TI  - Familial temporal lobe epilepsy in the 19th century.
AB  - PURPOSE: To draw attention to a publication showing that familial temporal lobe
      epilepsy had been described in 1895, considerably earlier than 1994, usually
      thought to be the date of the original account of the disorder METHODS:
      Examination of the contents of Sir James Crichton-Browne's Cavendish lecture on
      'Dreamy mental states' that was published in the Lancet in mid-1895 RESULTS: At a
      time when the clinical phenomena that later became associated with the idea of
      temporal lobe epilepsy were beginning to become known, Creighton-Browne described
      the presence of this disorder in members of four consecutive generations of a
      British family throughout the course of the 19th Century CONCLUSIONS: There is
      evidence that the genetic abnormality responsible for familial temporal epilepsy
      had probably appeared considerably earlier than hitherto thought.

PMID- 29172093
TI  - Quantification of perivascular spaces at 7T: A potential MRI biomarker for
      epilepsy.
AB  - PURPOSE: 7T (7T) magnetic resonance imaging (MRI) facilitates the visualization
      of the brain with resolution and contrast beyond what is available at
      conventional clinical field strengths, enabling improved detection and
      quantification of small structural features such as perivascular spaces (PVSs).
      The distribution of PVSs, detected in vivo at 7T, may act as a biomarker for the
      effects of epilepsy. In this work, we systematically quantify the PVSs in the
      brains of epilepsy patients and compare them to healthy controls. METHODS: T2
      weighted turbo spin echo images were obtained at 7T on 21 epilepsy patients and
      17 healthy controls. For all subjects, PVSs were manually marked on Osirix image
      analysis software. Marked PVSs with diameter>=0.5mm were then mapped by
      hemisphere and lobe. The asymmetry index (AI) was calculated for each region and
      the maximum asymmetry index (|AImax|) was reported for each subject. The
      asymmetry in epilepsy subjects was compared to that of controls, and the region
      with highest asymmetry was compared to the suspected seizure onset zone. RESULTS:
      There was a significant difference between the |AImax| in epilepsy subjects and
      in controls (p=0.016). In 72% of patients, the region or lobe of the brain
      showing maximum PVS asymmetry was the same as the region containing the suspected
      seizure onset zone. CONCLUSION: These findings suggest that epilepsy may be
      associated with significantly asymmetric distribution of PVSs in the brain.
      Furthermore, the region of maximal asymmetry of the PVSs may help provide
      localization or confirmation of the seizure onset zone.

PMID- 29172095
TI  - Innovations and pitfalls in the use of wearable devices in the prevention and
      rehabilitation of running related injuries.
AB  - Running-related injuries are common and are associated with a high rate of
      reoccurrence. Biomechanics and errors in applied training loads are often cited
      as causes of running-related injuries. Clinicians and runners are beginning to
      utilize wearable technologies to quantify biomechanics and training loads with
      the hope of reducing the incidence of running-related injuries. Wearable devices
      can objectively assess biomechanics and training loads in runners, yet guidelines
      for their use by clinicians and runners are not currently available. This article
      outlines several applications for the use of wearable devices in the prevention
      and rehabilitation of running-related injuries. Applications for monitoring of
      training loads, running biomechanics, running epidemiology, return to running
      programs and gait retraining are discussed. Best-practices for choosing and use
      of wearables are described to provide guidelines for clinicians and runners.
      Finally, future applications are outlined for this rapidly developing field.

PMID- 29172096
TI  - Serum agouti-related protein (AgRP) levels in bipolar disorder: Could AgRP be a
      state marker for mania?
AB  - Orexigenic and anorexigenic peptides, especially agouti-related protein (AgRP)
      and leptin, play important roles in the regulation of energy homeostasis in
      bipolar disorder. AgRP regulates energy metabolism by increasing appetite and
      decreasing energy expenditure. The resting energy expenditures of patients with
      manic bipolar disorder are higher than those of controls. Due to the effects of
      AgRP on energy expenditure and the increased physical activity of manic patients,
      we hypothesised that serum AgRP levels may be lower in manic patients than in
      euthymic patients and controls. There was a total of 112 participants, including
      47 patients in the manic group, 35 patients in the euthymic group and 30 healthy
      controls. For this study, serum AgRP, leptin, cholesterol, and cortisol levels
      were measured and compared between the groups. The serum AgRP, leptin, and
      cholesterol levels were significantly different between the groups. The serum
      AgRP levels of manic group were significantly lower than those of euthymic and
      control groups. The lower serum AgRP levels of manic patients could be indicators
      of impaired energy homeostasis during manic episodes. Since the serum AgRP levels
      of manic patients are lower than those of euthymic patients and controls, AgRP
      could be a state marker for manic episodes.

PMID- 29172097
TI  - Statin add-on therapy in the antipsychotic treatment of schizophrenia: A meta
      analysis.
AB  - A comprehensive meta-analysis of statin add-on therapy in the antipsychotic
      treatment of schizophrenia was conducted. Data from previous studies, prior to
      8/21/2017, was obtained from Scopus, PubMed, PsycINFO, and Cochrane Library. Both
      a systematic review and meta-analysis were conducted with patient data from
      randomized placebo-controlled trials (RCTs) to compare statins with placebo in
      order to calculate effect size. Across the five RCTs (mean duration: 9.2 weeks),
      236 adult patients with schizophrenia were randomly selected to receive either
      placebo (n=117) or statins (n=119). Pooled statin add-on therapy showed
      significant superiority over placebo in the improvement of Positive and Negative
      Syndrome Scale (PANSS) total scores (mean difference=-1.96; 95% confidence
      interval, -2.94 to -0.98; p<0.0001; I2=0%; N=4, n=174). However, there were no
      statistically significant differences in other efficacy outcomes between the two
      treatment groups. Statin did not have a significant difference in its incidence
      of discontinuation or have individual adverse events compared to placebo. Our
      results suggest that statins may have considerable potential as an add-on therapy
      for schizophrenia. However, determining the effectiveness of this treatment in
      clinical practice requires future investigation due to limitations of the current
      evidence-base including small sample, potential for publication and selection
      biases and short duration of follow-up.

PMID- 29172098
TI  - Social defeat as a mediator of the relationship between childhood trauma and
      paranoid ideation.
AB  - Social defeat, the subjective experience of viewing oneself as a failure or
      social outsider, is associated with various psychiatric disorders. Recent studies
      suggest that social defeat may play an important role in the development of
      psychotic disorders. This study examined the role of social defeat in the
      relationship between childhood trauma and paranoid ideation, a symptom of
      psychosis, in non-psychotic mental disorders. Psychiatric patients (N = 199)
      completed the Korean version of the Childhood Trauma Questionnaire, the Korean
      version of the Defeat Scale, and Restructured Clinical Scale 6 (Ideas of
      Persecution) of the Korean version of the Minnesota Multiphasic Personality
      Inventory-2. A partial correlation analysis revealed that childhood trauma was
      significantly related to social defeat and paranoid ideation after controlling
      for age and gender. Structural equation modeling confirmed that the relationship
      between childhood trauma and paranoid ideation was partially mediated by social
      defeat. Thus, social defeat is a possible psychological mechanism underlying the
      association between childhood trauma and paranoia.

PMID- 29172099
TI  - Associations between ADHD and eating disorders in relation to comorbid
      psychiatric disorders in a nationally representative sample.
AB  - The objective of this study was to examine whether previously observed
      associations of attention-deficit/hyperactivity disorder (ADHD) with eating
      disorders (EDs) are at least partially attributable to other underlying
      psychopathology. Data came from 4719 participants aged 18-44 years in the
      National Comorbidity Survey Replication and the National Survey of American Life.
      DSM-IV diagnoses were assessed using the World Health Organization Composite
      International Diagnostic Interview. Multinomial logistic regression assessed
      associations between DSM-IV lifetime and past-12 month diagnoses of ADHD with EDs
      in unadjusted models and in models adjusted for demographic variables and other
      psychopathology. Lifetime ADHD was strongly and significantly associated with
      lifetime bulimia nervosa (BN), binge eating disorder (BED), and any ED in
      unadjusted models, but not with anorexia nervosa or subthreshold BED. After
      adjusting for demographic variables and psychiatric comorbidities, all
      associations of lifetime ADHD with EDs were substantially attenuated, and only
      the association of ADHD with BN remained statistically significant. Similar
      results were found using past-12 month diagnoses. These results suggest that
      previously observed associations of ADHD with EDs might be due - at least in part
      - to additional psychiatric disorders that are often comorbid with both ADHD and
      EDs.

PMID- 29172100
TI  - Social identities and shared realities.
AB  - People are fundamentally motivated to establish a shared reality with others to
      validate their identity and experiences. Guided by social identity theory, we
      examine how social identity processes, such as self-categorization and
      depersonalization, create a shared identity and a sense of shared reality.
      Research demonstrates that internal states such as attitudes, feelings, and
      emotions are often shared among members of a group. Furthermore, research has
      shown that self-uncertainty motivates people to establish shared realities
      through group identification, often with highly entitative groups that are
      associated with a self-saturating reality that is shared absolutely. Finally, we
      review research on how group-defining norms that serve as the bases of these
      identity-related shared realities are constructed and communicated through group
      membership based influence.

PMID- 29172101
TI  - Design, synthesis and evaluation of resveratrol-indazole hybrids as novel
      monoamine oxidases inhibitors with amyloid-beta aggregation inhibition.
AB  - Novel hybrids with MAO and Abeta (1-42) self-aggregation inhibitory activities
      were designed and synthesized with the employment of indazole moiety and
      resveratrol. The biological screening results indicated that most compounds
      displayed potent inhibitory activity for Abeta (1-42) self-aggregation, and
      obvious selective inhibition to MAO-B. Among these compounds, compound 6e was the
      most potent inhibitor not only for hMAO-B (IC50 = 1.14 MUM) but also for Abeta (1
      42) self-aggregation (58.9% at 20 MUM). Molecular modeling and kinetic studies
      revealed that compound 6e was a competitive MAO-B inhibitor, which can occupy the
      active site of MAO-B, and interact with Abeta (1-42) via pi-pi and cation-pi
      stacking interactions. In addition, compound 6e had no toxicity on PC12 cells and
      could cross the BBB. Collectively, all these results suggested that compound 6e
      might be a promising multi-target lead compound worthy of further investigation.

PMID- 29172102
TI  - Influence of salicylic acid pretreatment on seeds germination and some defence
      mechanisms of Zea mays plants under copper stress.
AB  - The study was focused on the influence of salicylic acid (SA) on maize seeds
      germination and on some physiological and biochemical processes in maize plants
      growing in the hydroponic culture under copper (Cu) stress. A significant
      influence of SA pretreatment on the advanced induction of the maize seeds
      metabolic activity and the level of the endogenous SA in germinated seeds and
      developing roots have been stated. Although, the ability of maize seeds to uptake
      SA and accumulate it in the germinated roots was confirmed, the growth inhibition
      of Cu-stressed maize seedlings was not ameliorated by SA seeds pretreatment. Cu
      stressed plants exhibited a decrease in the photosynthetic pigment concentration
      and the increase in non-photochemical quenching (NPQ) - an indicator of an excess
      energy in PSII antenna assemblies lost as a heat. The amelioration effect of SA
      application was found only for carotenoids content which increased in stressed
      plants. It was also shown that maize roots growing in stress conditions
      significantly differed in the chemical composition in comparison to the roots of
      control plants, but the SA pretreatment did not affect these differences. On the
      other hand, it was found that SA seed pretreatment significantly influenced the
      ability of stressed plants to accumulate copper in the roots. It was stated that
      a higher level of exogenous SA application led to a lower accumulation of Cu ions
      in maize roots. Cu-stressed plants exhibited higher oxidative stress in roots
      than in leaves which was manifested as an increase in the concentration of
      hydrogen peroxide due to stress factor application. We observed an increase in
      catalase (CAT) activity in leaves of Cu-stressed plants which corresponded with a
      lower H2O2 content when compared with roots where the hydrogen peroxide level was
      higher, and the inhibition of the CAT activity was found. Furthermore, we found
      that the SA seed pretreatment led to a decrease in the H2O2 content in the roots
      of the Cu-stressed plants, but it did not influence the H2O2 level in leaves. The
      increase in hydrogen peroxide content in the roots of Cu-stressed plants
      correlated with a higher activity of the MnSODI and MnSODII isoforms. It was
      found that SA pretreatment caused a decrease in MnSODII activity accompanied by
      the decrease in H2O2 concentration. Achieved results indicated also that the
      changes in the chemical composition of the root tissue under copper stress
      constituted protection mechanisms of blocking copper flow into other plant
      organs. However, it might be assumed that the root tissue remodelling under Cu
      stress did not only prevent against the Cu ions uptake but also limited the
      absorption of minerals required for the normal growth leading to the inhibition
      of the plant development.

PMID- 29172103
TI  - Effect of cold stress on oxidative damage and mitochondrial respiratory
      properties in chickpea.
AB  - The present work aimed to characterize some of the mitochondrial and defense
      responses involved in tolerance to cold stress (CS) in tolerant (Sel96Th11439)
      and sensitive (ILC533) chickpea (Cicer arietinum L.) genotypes. During CS, the
      tolerant genotype prevented the H2O2 accumulation significantly; led to a
      decrease in electrolyte leakage index (ELI), which was a sign of relative
      acclimation of this genotype compared to sensitive one. A significant positive
      correlation between ELI and H2O2 (r0.01 = 0.86) content confirmed these results.
      Under cold, a significant increase in the alternative oxidase (AOX) activity was
      observed in tolerant genotype compared to sensitive one. In parallel, the high
      activity of superoxide dismutase (SOD) accompanied with catalase (CAT) and
      ascorbate peroxidase (APX) activities and also the extreme amounts of ascorbate
      and proline certified the active reactive oxygen species (ROS)-scavenging
      systems. There was a significant negative correlation between damage indices like
      H2O2 content and the activity of AOX (r0.01 = -0.79) as well as significant
      positive correlation between AOX activity with CAT (r0.05 = 0.61), SOD (r0.05 =
      0.51) and APX activity (r0.05 = 0.52). The increasing succinate dehydrogenase
      (CaSDH), CaAOX and cytochrome c oxidase (CaCOX) gene expression showed an
      enhancing response of respiration under CS in tolerant plants compared to
      sensitive ones. The increasing trend of phosphoenol pyruvate carboxylase (PEPC)
      activity in tolerant genotype particularly in the sixth day of CS indicated the
      recovered performance of metabolism pathways. Therefore, the increase of AOX
      activity along with other defensive mechanisms could be coordinately related to
      cold tolerance mechanisms in order to alleviate cold-induced oxidative stress in
      chickpea.

PMID- 29172104
TI  - Evaluation of metabolic changes in oxalate-rich plant Rumex obtusifolius L.
      caused by ion beam irradiation.
AB  - Some Rumex species such as sorrel are edible as baby leaf salad greens. On the
      other hand, Rumex plants accumulate soluble oxalate, a toxic metabolite which
      causes serious diseases such as renal syndrome. We attempted to produce low
      oxalate plants of R. obtusifolius, a perennial weed which has higher vitamin C
      and amino acid content and higher tolerance to stress than many other Rumex
      species. Ion beams are ionising radiation with high linear energy transfer that
      causes a wide spectrum of mutations. Thus, in the present study we evaluated the
      effects of ion beams on oxalate and other primary metabolites in leaves of R.
      obtusifolius using CE-MS. The results showed that oxalate content was increased
      by irradiation with carbon ion beams. Metabolome analysis revealed that ion beams
      affected carbon flow to the isocitrate pathway, which is involved in oxalate
      synthesis. These observations suggested that modulation of carbon flow to the
      isocitrate pathway is important to regulate oxalate levels in plants.

PMID- 29172105
TI  - When having two names facilitates lexical selection: Similar results in the
      picture-word task from translation distractors in bilinguals and synonym
      distractors in monolinguals.
AB  - We report five experiments using the picture-word task to examine lexical
      selection by comparing the effects of translation distractors in bilinguals and
      synonym distractors in monolinguals. Three groups of bilinguals named objects in
      their L1 or L2, and English monolinguals named objects using common names (e.g.,
      DOG="dog") or, in a novel manipulation, using synonymous alternative names (e.g.,
      DOG="hound", GLASSES="spectacles"). All studies produced strikingly similar
      results. When bilinguals named in L1, there was a small facilitation effect from
      translation distractors, but larger facilitation when they named in L2. When
      monolinguals produced common names, there was no reliable effect from synonym
      distractors, but facilitation when they produced alternative names. (There were
      also strong identity facilitation effects in all naming conditions.) We discuss
      the relevance of these results for the debate concerning the role of competition
      in lexical selection and propose that for speech production there are direct
      facilitatory connections between the lexical representations of translations in
      bilinguals (and between synonyms in monolinguals). The effects of synonyms in
      monolinguals appear to "simulate" the effects found for translations in
      bilinguals, which suggest that there are commonalities in monolingual and
      bilingual lexical selection.

PMID- 29172106
TI  - Characteristics of prospectively identified negative alcohol-related events among
      college students.
AB  - BACKGROUND: Throughout the first two years of college, the majority of drinkers
      experience one or more alcohol-related consequences. Research that examines the
      characteristics surrounding negative consequences typically utilizes global
      retrospective survey methods. The objective of the current study was to apply an
      event-based methodology to describe the circumstances of a recent drinking
      episode that resulted in one or more alcohol-related consequences among first-
      and second-year college students. METHODS: We used a prospective web-based survey
      method to identify participants (N=296) who had one or more alcohol-related
      consequences in the past week. Shortly after reporting the consequence(s),
      participants attended an in-person interview during which they described the
      circumstances that preceded and followed the consequence(s), including the use of
      alcohol and other substances, proximal contextual factors including peer
      drinking, the characteristics of the negative alcohol-related consequence(s), and
      the reaction of others to the event. RESULTS: The majority of participants
      reported experiencing the event at either their own (32.4%) or a friend's (32.8%)
      residence, and 87.1% of participants were with peers when the event happened.
      Most (85.0%) of the sample indicated that their closest friend knew about their
      event. CONCLUSION: The high peer involvement at all stages of the event suggest
      the potential for training college students to help each other avoid or prevent
      consequences.

PMID- 29172108
TI  - How lipase technology contributes to evolution of biodiesel production using
      multiple feedstocks.
AB  - Given the increasing interest in alternative processes for producing biodiesel,
      we focused on the latest screening of lipases and bioprocess design using
      multiple feedstocks. The implementation of lipase technology to the biodiesel
      industry is in the early stages. However, current research has made phenomenal
      advances in generating lipase variants and in engineering biodiesel production.
      The structural insights into lipase stability, together with primary screening,
      have opened up opportunities for acquiring lipase variants that are highly
      tolerant under industrially relevant conditions. The versatility of lipases is
      promising for process intensification, where time-consuming and costly steps can
      possibly be avoided. To judiciously overcome uncertainties in the biodiesel
      industry, further research on technology development integrated with supply chain
      models is necessary.

PMID- 29172109
TI  - The oral glucose test predicts laminitis risk in ponies fed a diet high in
      nonstructural carbohydrates.
AB  - The aim of this study was to investigate the relationship between laminitis
      development in ponies and insulin/glucose concentrations in response to the oral
      glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates
      (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h
      serum insulin concentrations ranging from 22 to 1,133 MUIU/mL were subjected to a
      diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin
      and glucose responses were measured on day 2 of the DCP. Clinical laminitis was
      diagnosed by blinded experts and confirmed radiographically. Basal ACTH levels
      and clinical signs were assessed to investigate concurrent putative pituitary
      pars intermedia dysfunction (PPID). The diet induced Obel grade 1 or 2 laminitis
      in 14 ponies (38%). The ponies that developed laminitis had higher maximum
      concentrations of blood glucose (P = 0.04) and serum insulin (P = 0.02) in
      response to the diet. The geometric mean (95% CI) blood glucose concentration for
      laminitis cases was 14.9 (12.9-17.2) mM, compared to 10.7 (9.2-12.5) mM for
      ponies who did not develop laminitis. Similarly, the geometric mean (95% CI) for
      serum insulin was 396 (301-520) MUIU/mL for laminitis cases, compared to 216 (148
      316) MUIU/mL for ponies who did not develop laminitis. Laminitis incidence was
      likewise associated with insulin concentrations measured during the OGT.
      Laminitis occurred at frequencies of 0% (0/7) if postdextrose insulin (MUIU/mL)
      was <50; 35% (8/23) if insulin was 50 to 195; and 86% (6/7) if insulin was >195
      MUIU/mL. Basal ACTH concentrations were above seasonally accepted reference
      ranges in 16/37 ponies, and 8 of these animals (50%) developed laminitis. This
      included all 5 ponies in the study that had clinical signs of PPID (100%). In
      contrast, hyperinsulinemia and laminitis occurred in only 3/11 ponies (27%) with
      elevated ACTH concentrations and no clinical signs of PPID (P = 0.009). Thus,
      laminitis occurrence was associated with higher glucose and insulin responses to
      both the OGT and challenge diet, and the frequency of laminitis can be predicted
      based on insulin and glucose hyperresponsiveness to these oral carbohydrate
      challenges.

PMID- 29172107
TI  - Immune responses in influenza A virus and human coronavirus infections: an
      ongoing battle between the virus and host.
AB  - Respiratory viruses, especially influenza A viruses and coronaviruses such as
      MERS-CoV, represent continuing global threats to human health. Despite
      significant advances, much needs to be learned. Recent studies in virology and
      immunology have improved our understanding of the role of the immune system in
      protection and in the pathogenesis of these infections and of co-evolution of
      viruses and their hosts. These findings, together with sophisticated molecular
      structure analyses, omics tools and computer-based models, have helped delineate
      the interaction between respiratory viruses and the host immune system, which
      will facilitate the development of novel treatment strategies and vaccines with
      enhanced efficacy.

PMID- 29172110
TI  - Role of luteal biosynthesis of prostaglandin F2alpha on function and structure of
      the corpus luteum during luteolysis in heifers.
AB  - The role of endogenous prostaglandin F2alpha (PGF) in the induction of luteolysis
      by exogenous PGF was studied by simultaneous inhibition of endogenous PGF with
      flunixin meglumine (FM). Groups were controls (n = 8), PGF treated (n = 8), and
      FM + PGF treated (n = 9). Treatments were given 10 d postovulation at hours 0, 8,
      and 16. The protocol was based on (1) the assumption that luteolytic
      characteristics of exogenous PGF would be altered if the synthesis of endogenous
      PGF is simultaneously inhibited and (2) the reports that luteolysis involves a
      direct effect of uterine PGF on large luteal cells followed by an effect of the
      large cells on the small cells. At hour 48, progesterone concentration was
      greater in the controls (7.6 +/- 0.8 ng/mL) than that in the FM + PGF group (3.0
      +/- 0.5 ng/mL) and lower in the PGF group (0.7 +/- 0.3 ng/mL) than in the FM +
      PGF group (interaction, P < 0.0001). The effects of each of the 3 groups on
      percentage change in CL volume were similar to the effects on progesterone. At
      hour 48, the percentage of CL tissue with color-Doppler signals of blood flow was
      similar between the controls (56.2% +/- 3.8%) and FM + PGF group (50.0% +/- 6.4%)
      and lowest in the PGF group (15.6% +/- 7.2%) (interaction, P < 0.0001). A
      resurgence in progesterone concentration began at hours 24 or 48 in 6 of 9
      heifers in the FM + PGF group compared to 0 of 8 heifers in each of the other
      groups (P < 0.007). The progesterone resurgence in the FM + PGF group was
      associated with the maintenance of percentage of CL tissue with blood-flow
      signals. The experimental hypothesis that an inhibitor of endogenous PGF reduces
      the luteolytic response to exogenous PGF was supported.

PMID- 29172111
TI  - Influence of dentin pretreatment with 2.5% titanium tetrafluoride on inhibiting
      caries at the tooth-restoration interface in situ.
AB  - OBJECTIVE: Investigate the effects of dentin pretreatment with 2.5% titanium
      tetrafluoride (TiF4) aqueous solution followed by two-step self-etching
      (CLE/Clearfil SE Bond) and one-step self-etching adhesive systems (SBU/Single
      Bond Universal) on carious lesion inhibition at the tooth-restoration interface
      using an in situ model. DESIGN: Sixty-four cavities at the enamel-dentin junction
      of dental fragments were randomly distributed according to groups (n=16): 1)
      TiF4+CLE; 2) TiF4+SBU; 3) CLE; 4) SBU. Cavities were restored using resin
      composite, and placed in intraoral palatal devices used by 16 volunteers for
      21days, to induce caries formation in situ. The fragments were then ground-flat
      to perform Knoop microhardness tests. Nine indentations were performed on each
      enamel and dentin substrate, subjacent to the restoration. Analysis of variance
      and Tukey's test were applied. RESULTS: Enamel: groups receiving TiF4 dentin
      pretreatment (regardless of adhesive system and tooth-restoration interface
      distance) presented higher hardness means at a depth of 25MUm from the outer
      tooth surface (p<0.0001). Dentin: groups receiving CLE presented higher means
      when applying TiF4 pretreatment, whereas groups restored with SBU presented
      higher means without pretreatment (p=0.0003). CONCLUSIONS: Dentin pretreatment
      with TiF4 inhibited demineralization of the enamel interface in situ, regardless
      of the adhesive, and TiF4 pretreatment followed by CLE application showed higher
      potential for inhibiting dentin demineralization at the interface.

PMID- 29172112
TI  - Cholesterol-lowering effects of dietary pomegranate extract and inulin in mice
      fed an obesogenic diet.
AB  - BACKGROUND: It has been demonstrated in animal studies that both polyphenol-rich
      pomegranate extract (PomX) and the polysaccharide inulin, ameliorate metabolic
      changes induced by a high-fat diet, but little is known about the specific
      mechanisms. OBJECTIVE: This study evaluated the effect of PomX (0.25%) and inulin
      (9%) alone or in combination on cholesterol and lipid metabolism in mice.
      METHODS: Male C57BL/6 J mice were fed high-fat/high-sucrose [HF/HS (32% energy
      from fat, 25% energy from sucrose)] diets supplemented with PomX (0.25%) and
      inulin (9%) alone or in combination for 4 weeks. At the end of intervention,
      serum and hepatic cholesterol, triglyceride levels, hepatic gene expression of
      key regulators of cholesterol and lipid metabolism as well as fecal cholesterol
      and bile acid excretion were determined. RESULTS: Dietary supplementation of the
      HF/HS diet with PomX and inulin decreased hepatic and serum total cholesterol.
      Supplementation with PomX and inulin together resulted in lower hepatic and serum
      total cholesterol compared to individual treatments. Compared to HF/HS control,
      PomX increased gene expression of Cyp7a1 and Cyp7b1, key regulators of bile acid
      synthesis pathways. Inulin decreased gene expression of key regulators of
      cholesterol de novo synthesis Srebf2 and Hmgcr and significantly increased fecal
      elimination of total bile acids and neutral sterols. Only PomX in combination
      with inulin reduced liver and lipid weight significantly compared to the HF/HS
      control group. PomX showed a trend to decrease liver triglyceride (TG) levels,
      while inulin or PomX-inulin combination had no effect on either serum or liver TG
      levels. CONCLUSION: Dietary PomX and inulin supplementation decreased hepatic and
      serum total cholesterol by different mechanisms and the combination leading to a
      significant enhancement of the cholesterol-lowering effect.

PMID- 29172113
TI  - Integrating self-management support for knee injuries into routine clinical
      practice: TRAK intervention design and delivery.
AB  - BACKGROUND: TRAK is a web-based intervention that provides knee patients with
      health information, personalised exercise plans and remote clinical support. The
      aim of this study was to fully define TRAK intervention content, setting and
      context and develop the training through an implementation study in a
      physiotherapy out-patient service. METHODS: A mixed methods study. Phase 1 was a
      qualitative interview study, whereby fifteen physiotherapists used TRAK for 1
      month with a patient of their choice. Interviews explored patient and
      physiotherapist views of TRAK intervention and training requirements. In Phase 2
      seventy-four patients were recruited, all received conventional physiotherapy, a
      subset of 48 patients used TRAK in addition to conventional Physiotherapy.
      Aspects of feasibility measured included: uptake and usage of TRAK. RESULTS:
      Patients and physiotherapists reported that TRAK was easy to use and highlighted
      the therapeutic benefit of the exercise videos and personalised exercise plans to
      remind them of their exercises and the correct technique. Patients reported
      needing to use TRAK with the guidance of their treating physiotherapist
      initially. Physiotherapists highlighted appointment time constraints and lack of
      familiarity with TRAK as factors limiting engagement. In Phase 2, 67% patients
      accessed TRAK outside of the clinical environment. A total of 91% of patients
      were given a personalised exercise plan, but these were only updated in 34% of
      cases. CONCLUSION: A comprehensive training package for patients and clinicians
      has been defined. The refined TRAK intervention is reported using the 'Template
      for Intervention Description and Replication in preparation for a definitive
      randomised control trial.

PMID- 29172114
TI  - Beamforming applied to surface EEG improves ripple visibility.
AB  - OBJECTIVE: Surface EEG can show epileptiform ripples in people with focal
      epilepsy, but identification is impeded by the low signal-to-noise ratio of the
      electrode recordings. We used beamformer-based virtual electrodes to improve
      ripple identification. METHODS: We analyzed ten minutes of interictal EEG of nine
      patients with refractory focal epilepsy. EEGs with more than 60 channels and 20
      spikes were included. We computed ~79 virtual electrodes using a scalar
      beamformer and marked ripples (80-250 Hz) co-occurring with spikes in physical
      and virtual electrodes. Ripple numbers in physical and virtual electrodes were
      compared, and sensitivity and specificity of ripples for the region of interest
      (ROI; based on clinical information) were determined. RESULTS: Five patients had
      ripples in the physical electrodes and eight in the virtual electrodes, with more
      ripples in virtual than in physical electrodes (101 vs. 57, p = .007). Ripples in
      virtual electrodes predicted the ROI better than physical electrodes (AUC 0.65
      vs. 0.56, p = .03). CONCLUSIONS: Beamforming increased ripple visibility in
      surface EEG. Virtual ripples predicted the ROI better than physical ripples,
      although sensitivity was still poor. SIGNIFICANCE: Beamforming can facilitate
      ripple identification in EEG. Ripple localization needs to be improved to enable
      its use for presurgical evaluation in people with epilepsy.

PMID- 29172115
TI  - RLS patients show better nocturnal performance in the Simon task due to
      diminished visuo-motor priming.
AB  - OBJECTIVE: The restless legs syndrome (RLS) is characterized by sensory-motor
      symptoms which usually occur predominantly at rest in the evening and at night.
      It is assumed that this circadian rhythm is caused by low dopamine levels in the
      evening. Yet, it has never been investigated whether RLS patients show diurnal
      variations in cognitive functions modulated by dopamine and what
      neurophysiological and functional neuroanatomical processes underlie such
      modulations. METHODS: We used a Simon task combined with EEG and source
      localization to investigate whether top-down response selection and/or automatic
      visuo-motor priming are subject to diurnal changes in RLS patients, as compared
      to matched healthy controls. RESULTS: We found that RLS patients showed better
      task performance due to reduced visuo-motor priming in the evening, as reflected
      by smaller early lateralized readiness potential (e-LRP) amplitudes and decreased
      activation of the superior parietal cortex and premotor cortex. Top-down response
      selection and early attentional processing were unaffected by RLS. CONCLUSIONS:
      Counterintuitively, RLS patients show enhanced task performance in the evening,
      i.e. when experiencing dopaminergic deficiency. Yet, this may be explained by
      deficits in visuo-motor priming that lead to reduced false response tendencies.
      SIGNIFICANCE: This study reveals a counterintuitive circadian variation of
      cognitive functions in RLS patients.

PMID- 29172116
TI  - Bilateral loss of cortical SEPs predict severe MRI lesions in neonatal hypoxic
      ischemic encephalopathy treated with hypothermia.
AB  - OBJECTIVE: The introduction of therapeutic hypothermia for neonatal hypoxic
      ischemic encephalopathy calls for reevaluation of the prognostic role of
      somatosensory evoked potentials (SEPs). METHODS: Among 80 consecutive neonates
      undergoing hypothermia for hypoxic-ischemic encephalopathy, 58 performed SEPs and
      MRI at 4-14 days of life and were recruited in this multicenter study. SEPs were
      scored as: 0 (bilaterally/unilaterally recorded N20) or 1 (bilaterally absent
      N20). The severity of brain injury was scored using MRI. RESULTS: Bilaterally
      absent N20 was observed in 10/58 neonates (17%); all had moderate/severe MRI
      abnormalities; 36/48 neonates (75%) with score 0 at SEPs had normal MRI. The
      positive predictive value of SEPs on MRI outcome was of 1.00, while the negative
      predictive value 0.72, sensitivity 0.48, specificity 1.00, with an accuracy of
      0.78 (p < .001). CONCLUSIONS: Bilateral absence of cortical SEPs predicts
      moderate/severe MRI pattern of injury. SIGNIFICANCE: Therapeutic hypothermia does
      not seem to significantly affect prognostic reliability of SEPs.

PMID- 29172117
TI  - The effect of surfactant adsorption on surface wettability and flow resistance in
      slit nanopore: A molecular dynamics study.
AB  - HYPOTHESIS: Due to large surface/volume ratio, fluid flow resistance in nanopores
      is affected dramatically by surfactants adsorption, which dictates wettability
      and friction. Surfactants with different aggregated morphology and molecular
      alignment at solid/water interface are expected to affect friction and mobility
      of surfactant adsorption layer, both of which should be possible to contribute to
      surfactant drag reduction mechanism in nanopores. Simulations: Molecular dynamics
      (MD) simulations were adopted to study the morphology of the adsorption layer of
      different types of surfactants on negatively charged hydrophilic silica surface
      and their effect on flow resistance in slit nanopores. FINDINGS: Flow resistance
      differs as surfactant adsorption morphologies vary. Adsorption layer composed of
      hemimicelles with "head on" orientation in low adsorption amount exhibits low
      flow resistance. As adsorption amount increases, adsorption layer evolves into
      the double layer in which less polar surfactant composition is found to be
      beneficial for improving hydrophobicity of pore wall and interfacial water
      diffusion. More ordered and tight intermolecular packing and high mobility of the
      adsorption layer are found to be propitious to reduce the flow friction.

PMID- 29172118
TI  - Rational and green synthesis of novel two-dimensional WS2/MoS2 heterojunction via
      direct exfoliation in ethanol-water targeting advanced visible-light-responsive
      photocatalytic performance.
AB  - Two-dimensional transition metal dichalcogenides (2D TMDs) and their
      heterostructures have by far stimulated growing research interests in the field
      of optoelectronics and photocatalysis. In this regard, scalable fabrication of 2D
      TMDs at an environmentally-benign and cost-effective manner via liquid phase
      exfoliation is a particularly fascinating concept. Herein we report a facile and
      green strategy to produce few-layered WS2 suspensions at a large scale by a
      direct exfoliation of commercial WS2 powders in water-ethanol mixtures. In turn,
      by making full use of the features of 2D layered WS2, a novel 2D WS2/MoS2
      composite was constructed for the first time via an in-situ hydrothermal reaction
      to grow MoS2 nanoflakes onto few-layered WS2 basal planes. The as-obtained
      WS2/MoS2 heterostructure was investigated for photocatalytic applications. Such a
      hybrid material demonstrated superior photocatalytic activity in the
      photocatalysis of organic dye molecules relative to that of pristine 2D WS2, MoS2
      and their physical mixtures. This enhancement was associated with the 2D WS2/MoS2
      heterostructuring effect. In addition, comparisons of the photocatalytic
      performances of our heterojunctions with those of recently reported 2D TMD-based
      hybrid materials manifested a significantly higher efficiency.

PMID- 29172119
TI  - Assembling particle clusters with incoherent 3D magnetic fields.
AB  - Directed assembly of particle suspensions in massively parallel formats, such as
      with magnetic fields, has application in rheological control, smart drug
      delivery, and active colloidal devices from optical materials to microfluidics.
      At the heart of these applications lies a control optimization problem for
      driving the assembly and dissolution of highly monodisperse particle clusters.
      For magnetic field control, most attention to-date has been centered around in
      phase coherent magnetic fields. Instead, we investigate a family of incoherent 3D
      magnetic fields that are capable of creating controlled and tunable particle
      assemblies such as dimers, trimers, and quadramers. These field functions can be
      tuned to assemble monodisperse clusters with long term stability and can quickly
      switch the clusters between different states. This subset of three-dimensional
      field functions that we have studied demonstrates the rich phase space available
      to tune colloidal suspensions with magnetic fields.

PMID- 29172120
TI  - 18F-labeled norepinephrine transporter tracer [18F]NS12137: radiosynthesis and
      preclinical evaluation.
AB  - INTRODUCTION: Several psychiatric and neurodegenerative diseases are associated
      with malfunction of brain norepinephrine transporter (NET). However, current
      clinical evaluations of NET function are limited by the lack of sufficiently
      sensitive methods of detection. To this end, we have synthesized exo-3-[(6
      [18F]fluoro-2-pyridyl)oxy]-8-azabicyclo[3.2.1]-octane ([18F]NS12137) as a
      radiotracer for positron emission tomography (PET) and have demonstrated that it
      is highly specific for in vivo detection of NET-rich regions of rat brain tissue.
      METHODS: We applied two methods of electrophilic, aromatic radiofluorination of
      the precursor molecule, exo-3-[(6-trimethylstannyl-2-pyridyl)oxy]-8-azabicyclo
      [3.2.1]octane-8-carboxylate: (1) direct labeling with [18F]F2, and (2) labeling
      with [18F]Selectfluor, a derivative of [18F]F2, using post-target produced
      [18F]F2. The time-dependent distribution of [18F]NS12137 in brain tissue of
      healthy, adult Sprague-Dawley rats was determined by ex vivo autoradiography. The
      specificity of [18F]NS12137 binding was demonstrated on the basis of competitive
      binding by nisoxetine, a known NET antagonist of high specificity. RESULTS:
      [18F]NS12137 was successfully synthesized with radiochemical yields of 3.9% +/-
      0.3% when labeled with [18F]F2 and 10.2% +/- 2.7% when labeled with
      [18F]Selectfluor. The molar activity of radiotracer was 8.8 +/- 0.7 GBq/MUmol
      with [18F]F2 labeling and 6.9 +/- 0.4 GBq/MUmol with [18F]Selectfluor labeling at
      the end of synthesis of [18F]NS12137. Uptake of [18F]NS12137 in NET-rich areas in
      rat brain was demonstrated with the locus coeruleus (LCoe) having the highest
      regional uptake. Prior treatment of rats with nisoxetine showed no detectable
      [18F]NS12137 in the LCoe. Analyses of whole brain samples for radiometabolites
      showed only the parent compound [18F]NS12137. Uptake of 18F-radioactivity in bone
      increased with time. CONCLUSIONS: The two electrophilic 18F-labeling methods
      proved to be suitable for synthesis of [18F]NS12137 with the [18F]Selectfluor
      method providing an approximate three-fold higher yield than the [18F]F2 method.
      As an electrostatically neutral radiotracer [18F]NS12137 crosses the blood-brain
      barrier and enabled specific labeling of NET-rich regions of rat brain tissue
      with the highest concentration in the LCoe.

PMID- 29172121
TI  - Marijuana use is associated with hypersensitivity to multiple allergens in US
      adults.
AB  - BACKGROUND: The recent legalization of marijuana use for both medical and
      recreational purposes in several states of the United Sates is expected to
      further increase the already high prevalence of marijuana use. Although allergic
      reactions are uncommon, the potential of marijuana use and cultivation to cause
      allergy should be considered. We aimed to investigate whether marijuana use is
      associated with the prevalence of sensitization to specific allergens. METHODS: A
      total of 2671 adults (aged 20-59 years) who participated in the 2005-2006
      National Health and Nutrition Examination Survey were included. Participants
      completed a questionnaire on marijuana use and underwent sensitization tests to
      19 specific allergens. Those who reported marijuana use for at least 1 day in the
      past 30 days were considered marijuana users. RESULTS: No difference was found in
      the history of allergy between marijuana users and non-users. Compared with
      marijuana non-users as a reference group, the adjusted odds ratio (AOR) of
      sensitization to a specific allergen among marijuana users was significantly
      greater for antibodies against the following: Alternaria alternata (AOR=1.67; 95%
      confidence interval (CI), 1.04-2.70), D. farinae (AOR=1.68; 95% CI, 1.27-2.22),
      D. pteronyssin (AOR=1.65; 95% CI, 1.32-2.06), ragweed (AOR=1.84; 95% CI, 1.30
      2.59), rye grass (AOR=1.49; 95% CI, 1.12-1.97), Bermuda grass (AOR=1.55; 95% CI,
      1.03-2.33), oak (AOR=1.76; 95% CI, 1.14-2.70), birch (AOR=2.09; 95% CI, 1.23
      3.55), peanut (AOR=1.91; 95% CI, 1.25-2.92), and cat dander (AOR=1.51; 95%
      CI=1.13-2.03). CONCLUSIONS: We provide preliminary findings to suggest that
      marijuana use is associated with sensitization to specific allergens, including
      molds, dust mites, plants, and cat dander.

PMID- 29172122
TI  - Brain substrates of early (4h) cigarette abstinence: Identification of treatment
      targets.
AB  - INTRODUCTION: Research indicates that overnight nicotine abstinence disrupts
      neural activity in the mesocorticolimbic reward network; however, less is known
      about the time course of abstinence-induced brain changes. To examine the
      potential neural effects of early abstinence, we used arterial spin labeling
      perfusion fMRI, to measure regional cerebral blood flow (rCBF) changes in the
      resting brain induced by 4h of nicotine abstinence. METHODS: In a repeated
      measures design, 5min of resting perfusion fMRI data were acquired in awake
      nicotine-dependent individuals (eyes open) during 'smoking as usual' (SMK) and
      following 4h of monitored nicotine abstinence (ABS) conditions (N=20). Conditions
      were compared using a paired t test in SPM8. Craving was assessed prior to each
      condition. RESULTS: Compared to SMK, ABS significantly increased craving and
      reduced rCBF in select regions, including the hippocampus and ventral striatum
      (cluster corr, alpha=0.01, 943 contiguous voxels). The magnitude of the
      abstinence-induced change in rCBF correlated with the magnitude of the change in
      craving across conditions in select regions, including the medial and lateral
      orbitofrontal cortices and the anterior ventral insula (r values ranging from
      0.59-0.74). CONCLUSIONS: Results show that as few as 4h of abstinence can reduce
      resting rCBF in multiple nodes of the brain's mesocorticolimbic network,
      disrupting neural processing. Identifying early withdrawal treatment targets has
      far-reaching implications, which include thwarting relapse proclivities. Results
      parallel those of the extant human literature and are in agreement with an
      extensive preclinical literature showing compromised mesolimbic dopaminergic
      function and impairments in reward function during nicotine withdrawal.

PMID- 29172124
TI  - Material mapping strategy to improve the predicted response of the proximal femur
      to a sideways fall impact.
AB  - Sideways falls are largely responsible for the highly prevalent osteoporotic hip
      fractures in today's society. These injuries are dynamic events, therefore
      dynamic FE models validated with dynamic ex vivo experiments provide a more
      realistic simulation than simple quasi-static analysis. Drop tower experiments
      using cadaveric specimens were used to identify the material mapping strategy
      that provided the most realistic mechanical response under impact loading. The
      present study tested the addition of compression-tension asymmetry, tensile bone
      damage, and cortical-specific strain rate dependency to the material mapping
      strategy of fifteen dynamic FE models of the proximal femur, and found improved
      correlations and reduced error for whole bone stiffness (R2 = 0.54, RSME =
      0.87kN/mm) and absolute maximum force (R2 = 0.56, RSME =0.57kN), and a high
      correlation in impulse response (R2 = 0.82, RSME =12.38kg/s). Simulations using
      fully bonded nodes between the rigid bottom plate and PMMA cap supporting the
      femoral head had higher correlations and less error than simulations using a
      frictionless sliding at this contact surface. Strain rates over 100/s were
      observed in certain elements in the femoral neck and trochanter, indicating that
      additional research is required to better quantify the strain rate dependencies
      of both trabecular and cortical bone at these strain rates. These results
      represent the current benchmark in dynamic FE modeling of the proximal femur in
      sideways falls. Future work should also investigate improvements in experimental
      validation techniques by developing better displacement measurements and by
      enhancing the biofidelity of the impact loading wherever possible.

PMID- 29172123
TI  - Existing and emerging therapies for managing constipation and diarrhea.
AB  - Functional bowel disorders (i.e., constipation and diarrhea) are characterized by
      abdominal pain, bloating, distention, and/or bowel habit abnormalities in the
      absence of obvious anatomic or physiologic abnormalities on routine diagnostic
      tests. These symptoms are attributable to gastrointestinal sensorimotor
      dysfunctions resulting from peripheral and/or central mechanisms. Available drugs
      target the underlying bowel disturbance (i.e., constipation, diarrhea, or both),
      supplemented when necessary by management of pain. Osmotic and stimulant
      laxatives, secretagogues, and serotonin 5-HT4 receptor agonists are approved for
      treating constipation. Loperamide, anticholinergic agents, rifaximin, bile-acid
      binding agents, eluxadoline, and clonidine are used to treat diarrhea. Several
      exciting new compounds, some of which have been evaluated in humans, are
      currently under development.

PMID- 29172125
TI  - Microtensile bond strength, 4-point bending and nanoleakage of resin-dentin
      interfaces: Effects of two matrix metalloproteinase inhibitors.
AB  - Chronic degradation of hybrid layer collagen by matrix metalloproteinases (MMPs)
      jeopardizes resin-dentin interfacial integrity and limits the durability of
      dental restorations. The 4-point bending strength (BS) is a valid but uncommon
      method of testing the mechanical behavior of resin-dentin interfaces. The present
      study aims to analyze the influence of two matrix metalloproteinase inhibitors on
      microtensile bond strength (uTBS), BS and nanoleakage. A total of 48M were
      divided into three groups according to bonding procedure. Teeth were horizontally
      sectioned to produce a flat dentin surface. In the control group, etch-and-rinse
      Prime&Bond One (Dentsply) bonding was used; in the self-etch group,
      methacryloyloxydodecylpyridinium bromide (MDPB)-containing Clearfil SE Protect
      (Kuraray) was used; and in the benzalkonium chloride (BAC)-etch group, BAC
      etchant (Bisco) was used. A Ceram.X-One (Dentsply) composite was built as three
      successive layers and was light-cured. Samples were sectioned to produce
      microrods that were randomly divided into two groups for analysis at baseline and
      after 6 months of water immersion (n = 32), plus one slab for nanoleakage
      analysis (n = 8) via scanning electron microscopy (SEM) and digital image
      analysis (Fiji). Data were analyzed using the Weibull distribution and a mixed
      model ANOVA with a post hoc Tukey test. All groups showed deterioration of the
      initial bonds. The self-etch group had a worse baseline uTBS than the control but
      had the best BS after aging. BAC-etch did not improve bond stability of etch-and
      rinse adhesive. The uTBS and BS test results after aging were moderately
      correlated. Mixed fractures prevailed with regard to uTBS, whereas adhesive
      fractures dominated with regard to BS. Nanoleakage was not eliminated in any
      group and increased after aging. MDPB self-etch resisted bond degradation better
      than etch-and-rinse adhesives, even after BAC-etching. Integrating BS in studies
      of uTBS and nanoleakage might provide more clinically relevant outcomes for
      predicting the performance of dental adhesives.

PMID- 29172127
TI  - Enantiomeric characterization and structure elucidation of LH601A using
      vibrational circular dichroism spectroscopy.
AB  - LH601A is a novel non-reactive chiral molecule inhibiting Keap1-Nrf2 protein
      protein interaction. The absolute configuration (AC) was independently determined
      in this study using vibrational circular dichroism (VCD) spectroscopy. Because of
      band overlapping and broadening in the IR spectrum, a direct VCD spectrum
      comparison method is devised without the conventional IR band alignment. Being an
      unbiased AC inquiry, all possible chiralities are evaluated based on the
      statistical analysis of VCD similarity, Sv. The AC of three-center stereoisomer
      LH601A is unambiguously assigned to (S,R,S). A comparative study was also carried
      out to investigate the structural and energy differences of calculated conformers
      using the polarized continuum model of dimethyl sulfoxide.

PMID- 29172126
TI  - Role of 6-O-alpha-maltosyl-beta-cyclodextrin in lysosomal cholesterol deprivation
      in Npc1-deficient Chinese hamster ovary cells.
AB  - We aimed to investigate whether 6-O-alpha-maltosyl-beta-cyclodextrin (Mal-betaCD)
      is incorporated into cells and lysosomes during the release of unesterified
      cholesterol in Npc1-deficient Chinese hamster ovary (CHO) cells (Npc1 KO cells)
      and CHO-JP17 cells (JP17 cells). Internalization of Mal-betaCD in cells and
      lysosomes and extracellular release of lysosomal unesterified cholesterol were
      demonstrated by LC/MS/MS and LC/MS, respectively. Internalization of Mal-betaCD
      was greater in Npc1 KO cells than in JP17 cells. The majority of internalized Mal
      betaCD in both cell types was metabolized by lysosomal alpha-glucosidase to 6-O
      alpha-D-glucosyl-beta-cyclodextrin (Glc-betaCD). However, Mal-betaCD did not
      directly enter the lysosomes prepared from cell homogenates. Mal-betaCD-treated
      Npc1 KO cells and JP17 cells both released Mal-betaCD and Glc-betaCD, together
      with unesterified cholesterol, out of cells. The release of unesterified
      cholesterol by Mal-betaCD in Npc1 KO cells was much greater than that in JP17
      cells. This study is the first to report the influx of Mal-betaCD into the
      lysosomes of Npc1 KO cells and JP17 cells, followed by generation of Glc-betaCD,
      and the efflux of Mal-betaCD/Glc-betaCD and unesterified cholesterol to the
      extracellular fluid, based on the quantitative LC/MS analysis.

PMID- 29172128
TI  - Probing the inhibitory potency of epigallocatechin gallate against human gammaB
      crystallin aggregation: Spectroscopic, microscopic and simulation studies.
AB  - Aggregation of human ocular lens proteins, the crystallins is believed to be one
      of the key reasons for age-onset cataract. Previous studies have shown that human
      gammaD-crystallin forms amyloid like fibres under conditions of low pH and
      elevated temperature. In this article, we have investigated the aggregation
      propensity of human gammaB-crystallin in absence and presence of epigallocatechin
      gallate (EGCG), in vitro, when exposed to stressful conditions. We have used
      different spectroscopic and microscopic techniques to elucidate the inhibitory
      effect of EGCG towards aggregation. The experimental results have been
      substantiated by molecular dynamics simulation studies. We have shown that EGCG
      possesses inhibitory potency against the aggregation of human gammaB-crystallin
      at low pH and elevated temperature.

PMID- 29172129
TI  - Effects of two-hour exposure to environmental and high concentrations of
      methylmercury on the transcriptome of the macrophyte Elodea nuttallii.
AB  - The effects of two methylmercury (CH3Hg+, MeHg) concentrations, representative of
      environmental level and extreme contamination, were investigated on the
      macrophyte Elodea nuttallii during a 2h-exposure combining transcriptomic (RNA
      Seq), physiological endpoints (pigment contents, activity of anti-oxidative
      stress enzymes) and bioaccumulation. Exposure to MeHg induced the up- and down
      regulation of numerous genes (4389 and 16853 for 10ngL-1 and 10MUgL-1 MeHg
      exposure, respectively) involved in sugar, amino acid and secondary metabolism
      (e.g. cinnamic acid, flavonoids) at both concentrations. Genes coding for
      photosynthesis, membrane integrity, metal homeostasis, water transport and anti
      oxidative enzymes were additionally up- and down-regulated at the higher
      concentration. At the physiological level, exposure to both MeHg concentrations
      resulted in a strong increase of anthocyanin content in shoots. Chlorophyll
      content and antioxidant enzyme activities were unchanged. The data suggest that
      the macrophyte was able to efficiently cope with the stress resulting from MeHg
      exposure, possibly by using anthocyanin as anti-oxidant and S-rich amino acids
      (such as cysteine and methionine) as chelators. Transcriptomics analysis enabled
      gaining novel insights on molecular effects of MeHg in primary producers, which
      are one of the main entry pathway of hazardous MeHg in aquatic food webs.

PMID- 29172130
TI  - Multigenerational effects of 4-methylbenzylidene camphor (4-MBC) on the survival,
      development and reproduction of the marine copepod Tigriopus japonicus.
AB  - One of the most widely used organic UV filters, 4-methylbenzylidene camphor (4
      MBC), is present at high concentrations in offshore waters. The marine copepod
      Tigriopus japonicus was exposed to different concentrations of 4-MBC (i.e., 0,
      0.5, 1, 5 and 10MUgL-1) for 4 consecutive generations (F0-F3) to evaluate the
      impact of 4-MBC on marine ecosystems. The results showed that in the F0
      generation, 4-MBC caused significant lethal toxicity in T. japonicas at
      concentrations of 5 and 10MUgL-1 and the nauplii were more sensitive to 4-MBC
      toxicity than the adults. However in the F1-F3 generations, 4-MBC exposure did
      not affect the survival rate. The hatching rate and the developmental duration
      from the nauplii to the copepodite (N-C) and from the nauplii to adult (N-A)
      decreased significantly in the F1-F2 generations and in the F2-F3 generations,
      respectively, even at the lowest exposure concentration (0.5MUgL-1). In the
      subsequent two generations (i.e., the F4-F5 generations) of recovery exposure in
      clean seawater, the growth rates of the original 4-MBC exposure groups were still
      faster than the control in both the N-C and N-A stages, suggesting possible
      transgenerational genetic and/or epigenetic changes upon chronic 4-MBC exposure.
      The expression of the ecdysone receptor gene was up-regulated by 4-MBC, which was
      consistent with the decrease of the N-C/N-A duration. In addition, 4-MBC may
      induce oxidative stress and trigger apoptosis in T. japonicas, resulting in
      developmental, reproductive and even lethal toxicity. A preliminary risk
      assessment suggested that under environmentally realistic concentrations, 4-MBC
      had significant potential to pose a threat to marine crustaceans and marine
      ecosystems.

PMID- 29172131
TI  - Nanoteamwork: covalent protein assembly beyond duets towards protein ensembles
      and orchestras.
AB  - Biological processes often depend on the harmonious interplay of multiple
      macromolecules. Biotechnology has had great success in applying and modifying
      individual components, but the building of multi-component teams is at an early
      stage. Cells are intelligent in sensing their environment, so manipulating just
      one signal can limit potency and promote side-effects for therapeutics. Here we
      critically assess the latest advances in irreversibly connecting individual
      protein units, through different spontaneous or catalysed reactions. Then we
      outline efforts to go beyond bipartite assembly, towards multimeric or sequence
      programmed architectures. These early steps will be put in context of the
      enormous opportunities for synthetic protein nanomachines, focusing on catalysis
      and the control of cell signalling for cancer and the immune system.

PMID- 29172132
TI  - Melatonin pretreatment improves vanadium stress tolerance of watermelon seedlings
      by reducing vanadium concentration in the leaves and regulating melatonin
      biosynthesis and antioxidant-related gene expression.
AB  - Vanadium (V) is an important heavy metal with ubiquitous presence in the Earth's
      crust, but limited information is available as to its effect on plants and
      management strategies. Melatonin is a widely studied biomolecule; it acts as an
      antioxidant and a signaling molecule that enhances the abiotic stress tolerance
      of plants. Melatonin improves copper, zinc, and cadmium tolerance in plants. In
      this study, we investigated the response of watermelon seedlings to V stress and
      the potential role of melatonin in enhancing V stress tolerance of watermelon
      seedlings. The results showed that seedlings pretreated with melatonin (0.1MUM)
      exposed to V (50mg/L) had a higher relative chlorophyll content (SPAD index),
      photosynthetic assimilation, and plant growth compared with non-melatonin
      pretreated seedlings. Melatonin pretreatment lowered leaf and stem V
      concentrations by reducing V transport from root to shoot. Melatonin pretreatment
      enhanced superoxide dismutase (SOD) and catalase (CAT) activities, and reduced
      the hydrogen peroxide (H2O2) and malondialdehyde (MDA) content of watermelon
      seedlings, by regulating melatonin biosynthesis and gene expression for
      superoxide dismutase, peroxidase, ascorbate peroxidase, glutathione peroxidase,
      and glutathione S-transferase. So far as we know, these results are the first
      evidence that melatonin improves plant growth of watermelon seedlings under
      vanadium stress conditions. Considering these observations, melatonin can be
      utilized to reduce the availability of V to plants, and improve plant growth and
      V stress tolerance.

PMID- 29172133
TI  - Cellular imaging and bactericidal mechanism of green-synthesized silver
      nanoparticles against human pathogenic bacteria.
AB  - In recent years, silver nanoparticles (AgNPs) have attracted significant
      attention in medicinal, biomedical, and pharmaceutical research owing to their
      valuable physicochemical and antibacterial properties. Leaf sap extract (LSE)
      from Aloe arborescens can be used as an active ingredient for different
      biological applications, including wound healing. In this study, we have
      investigated the use of LSE from A. arborescens as a reducing, stabilizing and
      capping agent to produce AgNPs during the so called "green synthesis" (G-AgNPs).
      The objective of this study was to prepare, characterize and evaluate the
      potential of G-AgNPs against human pathogenic bacteria for the intended use as
      treatment of infected wounds. When the mixture of silver nitrate solution and LSE
      was exposed to direct sunlight it yielded a rapid color change from colorless to
      reddish-brown, indicating the formation of G-AgNPs. Physicochemical
      characterization such as Single particle inductively coupled plasma mass
      spectrometry, High resolution transmission electron microscopy and surface
      chemistry studies (Fourier transform infrared spectroscopy and X-Ray diffraction)
      revealed a small size in the range of 38+/-2nm, smooth surface and existence of
      LSE on the G-AgNPs. G-AgNPs possessed good antibacterial activity against both
      Pseudomonas aeruginosa and Staphylococcus aureus. The flow cytometry study
      revealed the increased percentage of dead cells treated by G-AgNPs through cell
      membrane damage, and it was further confirmed by confocal laser scanning
      microscopy. Thus, the present study reveals that the novel G-AgNPs demonstrated
      effective antibacterial properties against both Gram-negative and Gram-positive
      bacterial strains and shows great potential for its use in the treatment of
      pathogen infected wounds.

PMID- 29172134
TI  - Synthesis, characterisation, cellular uptake and cytotoxicity of functionalised
      magnetic ruthenium (II) polypyridine complex core-shell nanocomposite.
AB  - The development of multifunctional nanoparticles comprising of a magnetic core in
      conjunction with appropriate molecules with capabilities to impart
      functionalities like luminescent, specific binding sites to facilitate attachment
      of moieties. This has attracted increasing attention and enables identification
      of promising candidates using for applications such as diagnostics and cure
      through early detection and localized delivery. Many studies have been performed
      on the synthesis and cellular interactions of core-shell nanoparticles, in which
      a functional inorganic core is coated with a biocompatible polymer layer that
      should reduce nonspecific uptake and cytotoxicity Here we report the synthesis
      and characterisation of multifunctional core-shell magnetic, luminescent
      nanocomposite (Fe3O4@SiO2@[Ru(Phen)3]2+@SiO2@NH2). Fe3O4 as core and a
      luminescent ruthenium (II) complex encapsulated with silica shell, and then it is
      functionalized by an amine group by APTMS. The magnetic, luminescent, and
      biological activity of this multifunctional nanocomposite have also been studied
      to prove the nanocomposite is biocompatible, cellular uptake. The synthesized
      nanocomposite was completely characterized by X-ray diffraction (XRD), Fourier
      transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM),
      vibrating sample magnetometer (VSM), and emission spectroscopy. MTT assay and
      cellular uptake by flow cytometry results proved that magnetic ruthenium (II)
      polypyridine complex - core shell nanocomposite has biocompatibility, minimum
      cytotoxicity and internalized inside B16F10 cells and confirms the potential
      biomedical applications.

PMID- 29172135
TI  - Potentiation by potassium iodide reveals that the anionic porphyrin TPPS4 is a
      surprisingly effective photosensitizer for antimicrobial photodynamic
      inactivation.
AB  - We recently reported that addition of the non-toxic salt, potassium iodide can
      potentiate antimicrobial photodynamic inactivation of a broad-spectrum of
      microorganisms, producing many extra logs of killing. If the photosensitizer (PS)
      can bind to the microbial cells, then delivering light in the presence of KI
      produces short-lived reactive iodine species, while if the cells are added after
      light the killing is caused by molecular iodine produced as a result of singlet
      oxygen-mediated oxidation of iodide. In an attempt to show the importance of PS
      bacterial binding, we compared two charged porphyrins, TPPS4 (thought to be
      anionic and not able to bind to Gram-negative bacteria) and TMPyP4 (considered
      cationic and well able to bind to bacteria). As expected TPPS4+light did not kill
      Gram-negative Escherichia coli, but surprisingly when 100mM KI was added, it was
      highly effective (eradication at 200nM+10J/cm2 of 415nm light). TPPS4 was more
      effective than TMPyP4 in eradicating the Gram-positive bacteria, methicillin
      resistant Staphylococcus aureus and the fungal yeast Candida albicans (regardless
      of KI). TPPS4 was also highly active against E. coli after a centrifugation step
      when KI was added, suggesting that the supposedly anionic porphyrin bound to
      bacteria and Candida. This was confirmed by uptake experiments. We compared the
      phthalocyanine tetrasulfonate derivative (ClAlPCS4), which did not bind to
      bacteria or allow KI-mediated killing of E. coli after a spin, suggesting it was
      truly anionic. We conclude that TPPS4 behaves as if it has some cationic
      character in the presence of bacteria, which may be related to its delivery from
      suppliers in the form of a dihydrochloride salt.

PMID- 29172136
TI  - IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy.
AB  - OBJECTIVE: Isocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an
      established association with preoperative seizures in patients with grades II-IV
      diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of
      postoperative seizure frequency. METHODS: This was a retrospective study.
      Patients with grades II-IV supratentorial diffuse glioma, immunohistochemistry
      results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively
      were included. The primary outcome was seizure frequency over the first 12
      postoperative months: Group A - postoperative seizure freedom; Group B - 1-11
      seizures over 12months (less than one seizure per month); and Group C - greater
      than one seizure per month. Rates of IDH1-R132H mutation were compared between
      the three outcome groups in univariate and multivariate analyses. Subgroup
      analysis was performed in 64 patients with IDH1/2 pyrosequencing data. RESULTS:
      One hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III,
      and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12months,
      compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H
      mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and
      70.0% (14/20) of Group C patients (p=0.001). On multivariate analysis, after
      controlling for preoperative seizure, grade, and temporal tumor location, IDH1
      R132H was associated with Group C when compared with both Group A (RR 4.75,
      p=0.032) and Group B (RR 9.70, p=0.012). In the subgroup with IDH1/2 molecular
      data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of
      Group C, and 87.5% (14/16) of Group C patients (p=0.004). SIGNIFICANCE: In
      patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated
      with a more severe phenotype of postoperative epilepsy. These findings support
      further research into IDH mutations, and the potential for an antiepileptic
      therapeutic effect of their inhibitors, in patients with glioma-associated
      epilepsy.

PMID- 29172137
TI  - The impact of stereotactic laser ablation at a typical epilepsy center.
AB  - PURPOSE: Stereotactic laser ablation (SLA) is a novel form of epilepsy surgery
      for patients with drug-resistant focal epilepsy. We evaluated one hundred
      consecutive surgeries performed for patients with epilepsy to address the impact
      of SLA on our therapeutic approach, as well as patient outcomes. METHODS: A
      retrospective, single center analysis of the last one hundred neurosurgeries for
      epilepsy was performed from 2013 to 2015. Demographics, surgical procedures, and
      postoperative measures were assessed up to 5years to compare the effect of SLA on
      outcome. Confidence intervals (CI) and comparative tests of proportions compared
      outcomes for SLA and resective surgery. Procedural categorical comparison used
      Chi-square and Kaplan-Meier curves. Student t-test was utilized for single
      variables such as age at procedure and seizure onset. RESULTS: One hundred
      surgeries for epilepsy yielded thirty-three SLAs and twenty-one resections with a
      mean of 21.7-month and 21.3-month follow-up, respectively. The temporal lobe was
      the most common target for SLA (92.6%) and resection (75%). A discrete lesion was
      present on brain magnetic resonance imaging (MRI) in 27/32 (84.4%) of SLA
      patients compared with 7/20 (35%) of resection patients with a normal MRI.
      Overall, 55-60% of patients became seizure-free (SF). Four of five patients with
      initial failure to SLA became SF with subsequent resection surgery. Complications
      were more frequent with resection although SF outcomes did not differ (Chi
      square; p=0.79). Stereotactic laser ablation patients were older than those with
      resections (47.0years vs. 35.4years, p=0.001). The mean length of hospitalization
      prior to discharge was shorter for SLA (1.18days) compared with open resection
      (3.43days; SD: 3.16 days) (p=0.0002). CONCLUSION: We now use SLA as a first line
      therapy at our center in patients with lesional temporal lobe epilepsy (TLE)
      before resection. Seizure-free outcome with SLA and resection was similar but
      with a shorter length of stay. Long-term follow-up is recommended to determine
      sustained SF status from SLA.

PMID- 29172138
TI  - Non-epileptic seizures in children: Views and approaches at a UK child and
      adolescent psychiatry conference.
AB  - PURPOSE: To describe clinical experiences of paediatric non-epileptic seizures
      (NES) among doctors attending a UK child and adolescent psychiatry conference.
      METHODS: Sixty-six participants completed a semi-structured bespoke
      questionnaire. Results are reported using descriptive statistics. RESULTS: Two
      thirds of respondents regarded the best name for the disorder to be "non
      epileptic seizures". Although most doctors saw new cases each year, two-thirds
      described their own service as poorly equipped to manage NES. Anti-epileptic
      drugs (AEDs) were commonly still being taken by children without epilepsy 6
      months after their diagnosis. Preferred treatment approaches included supportive
      case management and cognitive behavioural therapy. Joint working with paediatrics
      and liaison with schools were seen as important. CONCLUSION: Despite many
      clinicians having experience of the disorder, NES seemed to occupy a neglected
      status, often falling between paediatrics and child mental health, with
      inadequately defined care pathways leading to sub-optimal treatment. Re
      configuration of services to prioritise liaison with paediatrics and education
      may support development of effective treatment, thus maximising health, social
      and educational opportunities for young people and their families.

PMID- 29172139
TI  - Clinical experience with eslicarbazepine acetate in adults with sub-analysis of
      elderly.
AB  - PURPOSE: Eslicarbazepine acetate (ESL) is indicated for treatment of focal
      epilepsy. Our aim was to evaluate the effect and tolerability of ESL in elderly
      and younger adults. The primary objective was to measure changes in seizure
      frequency before and after at least six months of treatment. Secondary objective
      was to analyse the safety profile. Sub-analysis was performed in patients
      previously treated with oxcarbamazepine. METHOD: A single-centre, retrospective
      study of patients with focal epilepsy treated with ESL. Data were collected by
      reviewing the clinical and laboratory files. Seventy-two patients received ESL,
      of which 14 were >=60 years old, and were analysed for adverse effects. Fifty
      nine patients received treatment for >=6 months and were included in the
      evaluation of seizure frequency; in this group 12 were >=60 years old. RESULTS:
      Seizure frequency (n=59) was reduced for both young adults (< 60years) and
      elderly adults (>=60); both groups achieved better seizure control from an
      average of 2 to 0.5 (p-value: 0.002) and 3.5 to 0.65 (p-value:<0.05) seizures per
      month, respectively. Adverse effects leading to treatment discontinuation (n=72)
      were more frequent in elderly (42.9%) than in young adults (17.2%) (p-value
      0.04). There was no significant difference in mild adverse effects between young
      (15.5%) and elderly adults (14.3%). Most common adverse effects were somnolence,
      gastrointestinal disturbances and dizziness. CONCLUSIONS: The study indicates
      that ESL has an advantageous profile in relation to seizure control. The
      discontinuation rate might be higher in elderly than in younger adults. Further
      prospective studies are needed to confirm these conclusions.

PMID- 29172140
TI  - A novel electrochemical aptasensor for highly sensitive and quantitative
      detection of the streptomycin antibiotic.
AB  - In the present study, we report a facile approach to employ gold nanoparticle
      (AuNPs) and thiol graphene quantum dots (GQD-SH) as the nanomaterial for
      ultrasensitive detection of streptomycin (STR). Based on this strategy, a GQD-SH
      was immobilized onto the surface of a glassy carbon electrode (GCE). AuNPs have
      been immobilized on SH groups of GQDs through bonding formation of AuS and Apt
      have been loaded on the electrode surface through the interaction between thiol
      group of aptamer. By incubating STR as a target onto the surface of the prepared
      Apt/AuNPs/GQD-SH/GCE as a proposed nanoaptasensor, the Apt/STR complex was formed
      and the changes of the electrochemical signal were evaluated with the EIS
      technique. The proposed nanoaptasensor showed wide linear range from 0.1 to
      700pgml-1. Finally, the proposed nanoaptasensor was successfully applied for the
      determination of STR in real samples and satisfactory results were obtained.

PMID- 29172141
TI  - New sensor based on membranes with magnetic nano-inclusions for early diagnosis
      in periodontal disease.
AB  - A series of sodium selective membranes with magnetic nano-inclusions using p
      tertbutyl calix[4]arene as ionophore and polymeric matrix (polyvinyl chloride)
      have been developed, and the corresponding sodium selective sensors were obtained
      for the first time. A linear range was registered between 3.1 * 10-5 and 10
      1moldm-3 and near Nernstian electrochemical answer: 55.73mV/decade has been
      recoreded for PVC (polyvinyl chloride) - based sodium selective sensor, with a
      response time of 45s. Due to their small dimensions, sensors could be used for
      measuring ions from the gingival crevicular fluid directly into the peri-odontal
      pocket, avoiding the difficulties of collecting an appropriate amount of fluid
      for analysis. Alterations in the inorganic ions level could be evidenced with
      this new device, assisting the early diagnosis and prevention of periodontal
      disease.

PMID- 29172142
TI  - Detection of early stage prostate cancer by using a simple carbon nanotube@paper
      biosensor.
AB  - This study is an investigation for an inexpensive, simple and sensitive biosensor
      to detect prostate cancer using bioactivated-multi wall carbon nanotubes (MWCNTs,
      diameter of 20nm, length of 5um) and a micro-pore filter paper (pore size of
      0.45um). For the immunoassay of prostate specific antigen (PSA), which is a
      biomarker of prostate cancer, MWCNTs were activated with PSA antibody (monoclonal
      antibody of the prostate specific antigen) by using N-(3-dimethylaminopropyl)-N'
      ethylcarbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide sodium salt
      (NHSS). The activated MWCNTs were deposited on the micro-pore filter paper to use
      as a biosensor. The prepared biosensor can assay from 0 to 500ng/mL of PSA level
      within 2h with the detection limit of 1.18ng/mL by the measurement of resistance
      change. The resistance change was caused by site selective interaction between
      PSA and PSA-antigen with an inexpensive bench top digital multimeter (5 1/2
      digits). The detection range and sensitivity of the prepared sensor are good
      enough to diagnose the early stage of prostate cancer (> 4ng/mL of PSA). This
      paper-based biosensor is about 20 times cheaper (fabricated biosensor price: 2.4
      $) and over 10 times faster than enzyme-linked immunosorbent assay (ELISA), which
      is a general method for the detection of a specific protein in the modernized
      hospitals. Furthermore, the maximum detection limit is about 50 times higher than
      ELISA.

PMID- 29172143
TI  - Porous Ni0.1Mn0.9O1.45 microellipsoids as high-performance anode electrocatalyst
      for microbial fuel cells.
AB  - A novel bi-component composite of porous self-assembled micro-/nanostructured
      Ni0.1Mn0.9O1.45 microellipsoids as high-performance anode electrocatalyst for
      microbial fuel cells (MFCs) is successfully synthesized via a simple
      coprecipitation reaction in microemulsion and calcination method in air
      atmosphere. The morphology and structural characterization indicate that the as
      fabricated Ni0.1Mn0.9O1.45 product is consist of Mn2O3 and NiMn2O4 (n(Mn2O3):
      n(NiMn2O4) = 0.35: 0.1) and has a porous microellipsoidal morphology. The
      microellipsoids are compose of numerous layered micro-/nanostructured blocks and
      the special porous microellipsoids structure of Ni0.1Mn0.9O1.45 offers a large
      specific surface area for bacteria adhesion. The porous Ni0.1Mn0.9O1.45
      microellipsoids as anode electrocatalyst for MFCs exhibits excellent
      electrocatalytic activity to promote the extracellular electron transfer (EET)
      between the anode and bacteria, hence improves the performance of MFC. The MFC
      equipped with Ni0.1Mn0.9O1.45/CF anode achieves a maximum power density of 1.39
      +/- 0.02Wm-2, is significantly higher than that of commercial carbon felt anode.
      This work proposes a new method for the synthesis of high-performance and
      environmentally friendly anode electrocatalyst for MFCs.

PMID- 29172144
TI  - A molecularly imprinted electrochemiluminescence sensor based on upconversion
      nanoparticles enhanced by electrodeposited rGO for selective and ultrasensitive
      detection of clenbuterol.
AB  - A simple, efficient and sensitive molecularly imprinted electrochemiluminescence
      sensor (MIECLS) based on reduced graphene oxide (rGO) and upconversion
      nanoparticles (UCNPs) was developed for determination of clenbuterol (CLB). In
      this study, rGO generated by electrodeposition of graphene oxide not only acted
      as carrier for immobilizing UCNPs, but also had a significant impact in boosting
      electrochemiluminescence (ECL) response of UCNPs thanks to its high conductivity,
      superior electron transport rate and large specific surface area. UCNPs as an
      advanced ECL emitter possessed wonderful ECL performance. Furthermore, the
      introduction of molecularly imprinted polymers (MIP) endowed the ECL sensor a new
      character of specifically identifying analyte CLB. Under the optimal experimental
      conditions, the ECL signal was proportional to the logarithm of CLB concentration
      in the range of 10nM to 100uM with a low detection limit of 6.3nM. The proposed
      MIECLS combining the advantages of UCNPs-ECL and MIP exhibited good sensitivity,
      desirable selectivity and favorable stability, indicating enormous potential in
      the future of food safety detection.

PMID- 29172145
TI  - A novel 3D bioprinted flexible and biocompatible hydrogel bioelectronic platform.
AB  - Bioelectronics platforms are gaining widespread attention as they provide a
      template to study the interactions between biological species and electronics.
      Decoding the effect of the electrical signals on the cells and tissues holds the
      promise for treating the malignant tissue growth, regenerating organs and
      engineering new-age medical devices. This work is a step forward in this
      direction, where bio- and electronic materials co-exist on one platform without
      any need for post processing. We fabricate a freestanding and flexible hydrogel
      based platform using 3D bioprinting. The fabrication process is simple, easy and
      provides a flexible route to print materials with preferred shapes, size and
      spatial orientation. Through the design of interdigitated electrodes and heating
      coil, the platform can be tailored to print various circuits for different
      functionalities. The biocompatibility of the printed platform is tested using
      C2C12 murine myoblasts cell line. Furthermore, normal human dermal fibroblasts
      (primary cells) are also seeded on the platform to ascertain the compatibility.

PMID- 29172147
TI  - Interpreting solution X-ray scattering data using molecular simulations.
AB  - Small-angle and wide-angle X-ray scattering in solution (SAXS, WAXS, SWAXS) is an
      increasingly accurate method for obtaining information on biomolecular
      structures, ensembles, and time-resolved dynamics at near-native conditions.
      However, the interpretation of the solution scattering data by computational
      methods is complicated by the low information content of the data, by scattering
      contributions from the hydration layer, and by unknown systematic errors. In the
      light of available computational methods, we first review the main computational
      challenges with the interpretation of SWAXS data. Molecular dynamics (MD)
      simulations may help to overcome these challenges and guide the interpretation of
      SWAXS in multiple ways. The physical information in atomistic force fields
      complements the low-information SWAXS data; explicit-solvent MD may be used to
      predict solvent scattering, and the MD-related sampling methods may guide the
      structure refinement against SWAXS data.

PMID- 29172146
TI  - Development, validation and application of a micro-liquid chromatography-tandem
      mass spectrometry based method for simultaneous quantification of selected
      protein biomarkers of endothelial dysfunction in murine plasma.
AB  - The objective of this study was to develop and validate the method based on micro
      liquid chromatography-tandem mass spectrometry (microLC/MS-MRM) for simultaneous
      determination of adiponectin (ADN), von Willebrand factor (vWF), soluble form of
      vascular cell adhesion molecule 1 (sVCAM-1), soluble form of intercellular
      adhesion molecule 1 (sICAM-1) and syndecan-1 (SDC-1) in mouse plasma. The
      calibration range was established from 2.5pmol/mL to 5000pmol/mL for ADN;
      5pmol/mL to 5000pmol/mL for vWF; 0.375pmol/mL to 250pmol/mL for sVCAM-1 and sICAM
      1; and 0.25pmol/mL to 250pmol/mL for SDC-1. The method was applied to measure the
      plasma concentration of selected proteins in mice fed high-fat diet (HFD), and
      revealed the pro-thrombotic status by increased concentration of vWF (1.31+/-0.17
      nmol/mL (Control) vs 1.98+/-0.09 nmol/mL (HFD), p <0.05) and the dysregulation of
      adipose tissue metabolism by decreased concentration of ADN (0.62+/-0.08 nmol/mL
      (Control) vs 0.37+/-0.06 nmol/mL (HFD), p <0.05). In conclusion, the microLC/MS
      MRM-based method allows for reliable measurements of selected protein biomarkers
      of endothelial dysfunction in mouse plasma.

PMID- 29172148
TI  - Genetic characterization, micropropagation, and potential use for arsenic
      phytoremediation of Dittrichia viscosa (L.) Greuter.
AB  - In the last decade, many scientists have focused their attention on the search
      for new plant species that can offer improved capacities to reclaim polluted
      soils and waters via phytoremediation. In this study, seed batches from three
      natural populations of Dittrichia viscosa, harvested in rural, urban, and
      industrial areas of central and southern Italy, were used to: (i) evaluate the
      genetic and morphological diversity of the populations; (ii) develop an efficient
      protocol for in-vitro propagation from seedling microcuttings; (iii) achieve
      optimal acclimatization of micropropagated plants to greenhouse conditions; (iv)
      test the response to arsenic (As) soil contamination of micropropagated plants.
      The genetic biodiversity study, based on Random Amplification of Polymorphic DNA
      (RAPD), as well as the morphometric analysis of 20 seedlings from each population
      revealed some degree of differentiation among populations. Based on these data,
      the most biodiverse plants from the three populations (10 lines each) were
      clonally multiplied by micropropagation using microcuttings of in-vitro grown
      seedlings. Three culture media were tested and Mureshige and Skoog medium was
      chosen for both seedling growth and micropropagation. The micropropagated plants
      responded well to greenhouse conditions and over 95% survived the acclimatization
      phase. Four clones were tested for their capacity to grow on soil spiked with
      NaAsO2 and to absorb and accumulate the metalloid. All clones tolerated up to
      1.0mg As. At the end of the trial (five weeks), As was detectable only in leaves
      of As-treated plants and concentration varied significantly among clones. The
      amount of As present in plants (leaves) corresponded to ca. 0.10-1.7% of the
      amount supplied. However, As was no longer detectable in soil suggesting that the
      metalloid was taken up, translocated and probably phytovolatilized.

PMID- 29172149
TI  - Exposure to deltamethrin induces oxidative stress and decreases of energy reserve
      in tissues of the Neotropical fruit-eating bat Artibeus lituratus.
AB  - Deltamethrin (DTM) is a synthetic pyrethroid insecticide highly used by farmers
      and home users. This pesticide has lipophilic properties that facilitate a high
      absorption and can cause toxicity in non-target organisms. During foraging, the
      fruit-eating bats Artibeus lituratus are exposed to pesticides. However, the
      knowledge of the toxicity of pesticides on the physiology of bats is relatively
      scarce. This study aimed to check the toxicity of short-term exposure to low
      concentration of DTM on fruit-eating bat A. lituratus. After seven days of
      exposure to two doses of DTM (0.02 and 0.04mg/kg of papaya), the fruit bats
      showed an increase in the enzyme aspartate aminotransferase, alanine
      aminotransferase, and hyperglycemia. The liver and pectoral muscle presented
      oxidative stress. In the liver, the hydrogen peroxide (H2O2) and nitric oxide
      (NO) were increased as well as the antioxidant glutathione (GSH), the activity of
      glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT)
      but in a lesser extent. Yet, total lipids were increased while hepatic glycogen
      content is reduced. The pectoral muscle showed NO, SOD, CAT, malondialdehyde
      (MDA), and carbonyl increased protein levels in both concentrations of DTM. All
      these results show that low doses of DTM can cause hepatic and muscular toxicity
      and induce changes in carbohydrate metabolism. Physiological changes caused by
      exposure to DTM in bats may have direct consequences in flight capacity,
      reproduction, and metabolism of these animals.

PMID- 29172150
TI  - Effects of ibuprofen and carbamazepine on the ion transport system and fatty acid
      metabolism of temperature conditioned juveniles of Solea senegalensis.
AB  - The increasing presence of pharmaceuticals in aquatic environments in the last
      decades, derived from human and veterinary use, has become an important
      environmental problem. Previous studies have shown that ibuprofen (IB) and
      carbamazepine (CBZ) modify physiological and biochemical processes in Senegalese
      sole (Solea senegalensis) in a temperature-dependent manner. In other
      vertebrates, there is evidence that both of these pharmaceuticals interfere with
      the 'arachidonic acid (AA) cascade', which is responsible for the biosynthesis of
      numerous enzymes that are involved in the osmoregulatory process. The present
      work aims to study the temperature-dependent effects of these two pharmaceuticals
      on several biochemical and molecular parameters in Senegalese sole. Regarding
      osmoregulation, Na+, K+ -ATPase enzyme activity was determined in the gills,
      kidney and intestine, and the expressions of both Na+, K+ -ATPase 1alpha-subunit
      isoforms (ATP1A1a and ATP1A1b) were quantified in gills. Gill prostaglandin
      endoperoxide synthase-2 (PTGS2) gene expression and fatty acid composition were
      selected to determine the interference of both pharmaceuticals with the AA
      cascade. Senegalese sole juveniles, acclimatised at 15 degrees C or 20 degrees C,
      were exposed through intraperitoneal injection to IB (10mg/kg) and CBZ (1mg/kg)
      for 48h. Non-injected fish (Control) and those injected with the carrier
      (sunflower oil; S.O.), acclimated at each of the two temperatures, were used for
      comparison. The results show that IB directly affected the osmoregulatory
      mechanisms that alter gill and intestine Na+, K+ -ATPase activities. In addition,
      the copy number of ATP1A1a was higher at 20 degrees C than at 15 degrees C, which
      could be a direct response to the temperature variation. The gene expression of
      PTGS2 was affected by neither drug administration nor acclimation temperature.
      Nevertheless, detailed analysis of AA and eicosapentaenoic acid (EPA) percentages
      revealed a CBZ-derived effect in the fatty acid composition of the gills.

PMID- 29172151
TI  - Oxidative stress-driven pulmonary inflammation and fibrosis in a mouse model of
      human ataxia-telangiectasia.
AB  - Lung failure is responsible for significant morbidity and is a frequent cause of
      death in ataxia-telangiectasia (A-T). Disturbance in the redox balance of
      alveolar epithelial cells must be considered as a causal factor for respiratory
      disease in A-T. To investigate bronchoalveolar sensitivity to reactive oxygen
      species (ROS) and ROS-induced DNA damage, we used bleomycin (BLM) to induce
      experimental inflammation and fibrotic changes in the Atm-deficient mouse model.
      BLM or saline was administered by oropharyngeal instillation into the lung of Atm
      deficient mice and wild-type mice. Mice underwent pulmonary function testing at
      days 0, 9, and 28, and bronchoalveolar lavage (BAL) was analysed for cell
      distribution and cytokines. Lung tissue was analysed by histochemistry. BLM
      administration resulted in a tremendous increase in lung inflammation and
      fibrotic changes in the lung tissue of Atm-deficient mice and was accompanied by
      irreversible deterioration of lung function. ATM (ataxia telangiectasia mutated)
      deficiency resulted in reduced cell viability, a delay in the resolution of
      gammaH2AX expression and a significant increase in intracellular ROS in pulmonary
      epithelial cells after BLM treatment. This was confirmed in the human epithelial
      cell line A549 treated with the ATM-kinase inhibitor KU55933. Our results
      demonstrate high bronchoalveolar sensitivity to ROS and ROS-induced DNA damage in
      the Atm-deficient mouse model and support the hypothesis that ATM plays a pivotal
      role in the control of oxidative stress-driven lung inflammation and fibrosis.

PMID- 29172152
TI  - Safety and immune regulatory properties of canine induced pluripotent stem cell
      derived mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo
      and can suppress T cell proliferation and dendritic cell activation in vitro.
      Currently, most MSC for clinical usage are derived from younger donors, due to
      ease of procurement and to the superior immune modulatory activity. However, the
      use of MSC from multiple unrelated donors makes it difficult to standardize study
      results and compare outcomes between different clinical trials. One solution is
      the use of MSC derived from induced pluripotent stem cells (iPSC); as iPSC
      derived MSC have nearly unlimited proliferative potential and exhibit in vitro
      phenotypic stability. Given the value of dogs as a spontaneous disease model for
      pre-clinical evaluation of stem cell therapeutics, we investigated the functional
      properties of canine iPSC-derived MSC (iMSC), including immune modulatory
      properties and potential for teratoma formation. We found that canine iMSC
      downregulated expression of pluripotency genes and appeared morphologically
      similar to conventional MSC. Importantly, iMSC retained a stable phenotype after
      multiple passages, did not form teratomas in immune deficient mice, and did not
      induce tumor formation in dogs following systemic injection. We concluded
      therefore that iMSC were phenotypically stable, immunologically potent, safe with
      respect to tumor formation, and represented an important new source of cells for
      therapeutic modulation of inflammatory disorders.

PMID- 29172154
TI  - Specific binding of human C-reactive protein towards supported monolayers of
      binary and engineered phospholipids.
AB  - Circulating C-reactive protein (CRP) recognizes altered plasma membranes and
      activates complements systems in the acute phase of inflammation and infection in
      human. We have shown previously the calcium-independent adsorption of CRP toward
      1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and
      lysophosphatidylcholine (LPC) on supported phospholipid monolayers. Here, we
      extended our study to other phospholipids and additives to elucidate the pattern
      recognition of CRP using a surface plasmon resonance biosensor. Surface density
      and lateral fluidity depended on the type of phospholipids in the monolayers as
      characterized by SPR and fluorescence recovery after photobleaching measurements.
      CRP recognized 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS) and 1
      palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) in the supported
      POPC monolayers without calcium at pH 7.4 and 5.5. As opposed to LPC, CRP did not
      recognize 3-sn-lysophosphatidylethanolamine in the POPC monolayers in calcium
      free conditions. While, the addition of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoethanolamine (POPE) or sphingomyelin to supported POPC monolayers blocked
      CRP adsorption. Calcium-dependent CRP binding was observed only at pH 5.5 on
      supported monolayers of engineered phospholipids with inverted headgroups
      relative to POPC. The complement 1q (C1q) protein recognized the active form of
      CRP on the supported phospholipid monolayers. The discovery of CRP recognition
      with these phospholipids aids our understanding of the activation dynamics of CRP
      with phospholipid-based biomaterials when used during the acute phase.

PMID- 29172153
TI  - Ajmaline blocks INa and IKr without eliciting differences between Brugada
      syndrome patient and control human pluripotent stem cell-derived cardiac
      clusters.
AB  - The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent
      type I ECG in Brugada syndrome (BrS) patients, although its mode of action is
      poorly characterised. Our aims were to identify ajmaline's mode of action in
      human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and
      establish a simple BrS hiPSC platform to test whether differences in ajmaline
      response could be determined between BrS patients and controls. Control hiPSCs
      were differentiated into spontaneously contracting cardiac clusters. It was found
      using multi electrode array (MEA) that ajmaline treatment significantly
      lengthened cluster activation-recovery interval. Patch clamping of single CMs
      isolated from clusters revealed that ajmaline can block both INa and IKr.
      Following generation of hiPSC lines from BrS patients (absent of pathogenic SCN5A
      sodium channel mutations), analysis of hiPSC-CMs from patients and controls
      revealed that differentiation and action potential parameters were similar.
      Comparison of cardiac clusters by MEA showed that ajmaline lengthened activation
      recovery interval consistently across all lines. We conclude that ajmaline can
      block both depolarisation and repolarisation of hiPSC-CMs at the cellular level,
      but that a more refined integrated tissue model may be necessary to elicit
      differences in its effect between BrS patients and controls.

PMID- 29172155
TI  - Controlling insulin release from reverse hexagonal (HII) liquid crystalline
      mesophase by enzymatic lipolysis.
AB  - In the present study we aimed to control insulin release from the reverse
      hexagonal (HII) mesophase using Thermomyces lanuginosa lipase (TLL) in the
      environment (outer TLL) or within the HII cylinders (inner TLL). Two insulin
      loaded systems differing by the presence (or absence) of phosphatidylcholine (PC)
      were examined. In general, incorporation of PC into the HII interface (without
      TLL) increased insulin release, as a more cooperative system was formed. Addition
      of TLL to the systems' environments resulted in lipolysis of the HII structure.
      In the absence of PC, the lipolysis was more dominant and led to a significant
      increase in insulin release (50% after 8h). However, the presence of PC
      stabilized the interface, hindering the lipolysis, and therefore no impact on the
      release profile was detected during the first 8h. Entrapment of TLL within the
      HII cylinders (with and without PC) drastically increased insulin release in both
      systems up to 100%. In the presence of PC insulin released faster and the
      structure was more stable. Consequently, the presence of lipases (inner or outer)
      both enhanced the destruction of the carrier, and provided sustained release of
      the entrapped insulin.

PMID- 29172156
TI  - Comparative investigation of X-ray contrast medium degradation by UV/chlorine and
      UV/H2O2.
AB  - The degradation of iopamidol and diatrizoate sodium (DTZ) by UV/chlorine was
      carried out according to efficiency, mechanism, and oxidation products, and
      compared to that by UV/H2O2. The pseudo-first order rate (k') of iopamidol and
      DTZ was accelerated by UV/chlorine compared to that by UV and chlorine alone. k'
      of iopamidol and DTZ by UV/chlorine increased with increasing chlorine dosage.
      Both of iopamidol and DTZ could not be effectively removed by UV/H2O2 compared to
      that by UV/chlorine. Secondary radicals (Cl2- and ClO) rather than primary
      radicals (HO and Cl) were demonstrated to be mainly responsible for the enhanced
      removal of iopamidol and DTZ by UV/chlorine. The oxidation products of iopamidol
      and DTZ resulting from UV/chlorine and UV/H2O2 process were identified, and
      differences existed in the two systems. IO3- (the desired sink of I-) was the
      major inorganic product in the UV/chlorine process whereas I- was the predominant
      inorganic product in the UV/H2O2 process. The formation of chlorine-containing
      products during the degradation of iopamidol and DTZ by UV/chlorine was also
      observed. H-abstraction, additions, de-iodination were shared during the
      degradation of iopamidol by UV/chlorine and UV/H2O2. Neutral pH condition was
      preferred for the removal of iopamidol and DTZ by UV/chlorine. UV/chlorine could
      also be applied in real waters for the removal of iopamidol and DTZ.

PMID- 29172157
TI  - New particle formation and growth at a suburban site and a background site in
      Hong Kong.
AB  - Atmospheric nanoparticles have great impacts on human health and global climate
      change. The number concentrations and size distributions of nanoparticles in the
      size range of 5.5-350.4 nm were detected at a background site and a suburban site
      in Hong Kong from summer to winter in 2011 and in autumn of 2013, respectively.
      Significantly higher particle number concentrations in all modes were observed at
      the suburban site (p < 0.05) during the sampling periods, possibly due to
      stronger primary emissions/regional transport and more intensive new particle
      formation (NPF). Particle number concentrations were much enhanced under
      northerly winds at both sites, resulting from regional transport of Aitken and
      accumulation mode particles, enhanced local NPF and occasionally low condensation
      sink. NPF was mainly limited by the precursors of condensable vapors and
      oxidative capacity of the atmosphere at the background site and the suburban
      site, respectively. In most cases, the formation rate of 5.5 nm particles was a
      function of sulfuric acid vapor to the power of 1.32 +/- 0.34 at the background
      site and 0.81 +/- 0.31 at the suburban site, abiding by the cluster activation
      theory. However, ozonolysis of monoterpenes (particularly alpha-pinene) might
      also drive NPF, particularly in the afternoon. These reactions also contributed
      to the growth of nucleation mode particles, which was largely explained by
      sulfuric acid vapor (73.6 +/- 10% at the background site and 60.4 +/- 9.8% at the
      suburban site). In contrast, the oxidations of isoprene, beta-pinene and
      aromatics (particularly xylenes and trimethylbenzenes) were found to participate
      in the growth of Aitken mode particles.

PMID- 29172158
TI  - Facing the rain after the phase out: Performance evaluation of alternative
      fluorinated and non-fluorinated durable water repellents for outdoor fabrics.
AB  - Fluorinated durable water repellent (DWR) agents are used to obtain water and
      stain repellent textiles. Due to the on-going phase-out of DWRs based on side
      chain fluorinated polymers (SFP) with "long" perfluoroalkyl chains, the textile
      industry lacks suitable alternatives with comparable material characteristics.
      The constant development and optimization of SFPs for textile applications
      initiated more than half a century ago has resulted in a robust and very
      efficient DWR-technology and textiles with exceptional hydro- and oleo-phobic
      properties. The industry is now in the predicament that the long-chain SFPs with
      the best technical performance have undesirable toxicological and environmental
      behaviour. This study provides a comprehensive overview of the technical
      performance of presently available fluorinated and non-fluorinated DWRs as part
      of a chemical alternatives assessment (CAA). The results are based on a study
      with synthetic outdoor fabrics treated with alternative DWRs and tested for
      repellency using industrial standard and complementary methods. Using this
      approach, the complex structure-property relationships of DWR-polymers could be
      explained on a molecular level. Both short-chain SFPs and non-fluorinated DWRs
      showed excellent water repellency and durability in some cases while short-chain
      SFPs were the more robust of the alternatives to long-chain SFPs. A strong
      decline in oil repellency and durability with perfluoroalkyl chain length was
      shown for SFP DWRs. Non-fluorinated alternatives were unable to repel oil, which
      might limit their potential for substitution in textile application that require
      repellency towards non-polar liquids.

PMID- 29172159
TI  - Electro-oxidation of Ofloxacin antibiotic by dimensionally stable Ti/RuO2 anode:
      Evaluation and mechanistic approach.
AB  - Present study investigates the potential of Ti/RuO2 electrode for degradation and
      mineralization of Ofloxacin (OFLX) antibiotic from synthetic wastewater by
      electro-oxidation (EO) method, not reported earlier. Effects of various EO
      parameters such as applied current (I), initial pH, initial OFLX concentration
      (C0) and supporting electrolyte concentration on %OFLX removal efficiency and
      %TOC removal efficiency were systematically studied and reported. Decay kinetics
      of OFLX by varying C0 and applied I were also studied. Additionally,
      mineralization current efficiency and specific energy consumption of OFLX
      mineralization were evaluated. Moreover, mode of oxidation method involved
      (direct and/or indirect oxidation) was also explored. Major OFLX transformation
      products during EO were identified using UPLC-Q-TOF-MS, and possible degradation
      reaction mechanism was proposed. Furthermore, operating cost analysis was
      performed to check the economic feasibility of the EO process. The optimum pH and
      current (I) were found to be ~6.8 (natural pH of OFLX wastewater) and 1 A,
      respectively. Mineralization current efficiency decreased from 7.8% to 4.9% with
      increase in I value from 0.25 to 1 A. ~80% of OFLX removal in 30 min of
      electrolysis and 46.3% TOC removal in 240 min of electrolysis at I = 1 A were
      observed. Pseudo-first-order kinetic model best fitted the experimental data
      showing R2 value ~ 0.99 for all the Co and applied I studied.

PMID- 29172160
TI  - The neurocognitive effects of a conducted electrical weapon compared to high
      intensity interval training and alcohol intoxication - implications for Miranda
      and consent.
AB  - While the physiologic effects of conducted electrical weapons (CEW) have been the
      subjects of numerous studies over nearly two decades, their effects on
      neurocognitive functioning, both short-term and long-term, have only recently
      been studied. In a 2014 study involving use-of-force scenarios, including a CEW
      scenario, we found that there was a decline in neurocognitive performance
      immediately post-scenario in all groups; however this effect was transient, of
      questionable clinical/legal significance, not statistically different between the
      groups, and, returned to baseline by one hour post-scenario. Two subsequent
      studies by other authors have also found transient neurocognitive effects in the
      immediate post-exposure period; however, in one study, the effect was greater in
      one measure (of 5) for the CEW compared to exertion, and the authors suggested
      that this effect could have implications for the Miranda waiver obtained before
      custodial interrogation as well as consent. In our current study, we compared the
      neurocognitive effects of an exposure to a CEW to another exertion regimen, as
      well as to alcohol intoxication given the latter has significant established case
      law with regard to the Miranda waiver and consent. Such a comparison may offer
      more insight into the clinical/legal significance of any measured changes. As
      with the prior studies, the neurocognitive performance decrements of the CEW and
      exertion regimens, found only in one measure in this study (of three), were
      transient, and here, non-significant. Only alcohol intoxication resulted in
      statistically significant performance declines across all measures and these were
      persistent over the study period. Given that the neurocognitive changes
      associated with the CEW were non-significant, but were significant for alcohol
      intoxication, and given that current case law does not use intoxication as a per
      se or bright line barrier to Miranda and consent, our results do not suggest that
      a CEW exposure should preclude waiving of Miranda rights or obtaining consent.

PMID- 29172161
TI  - Urban upbringing and childhood respiratory and allergic conditions: A multi
      country holistic study.
AB  - OBJECTIVE: We integratively assessed the effect of different indoor and outdoor
      environmental exposures early in life on respiratory and allergic health
      conditions among children from (sub-) urban areas. METHODS: This study included
      children participating in four ongoing European birth cohorts located in three
      different geographical regions: INMA (Spain), LISAplus (Germany), GINIplus
      (Germany) and BAMSE (Sweden). Wheezing, bronchitis, asthma and allergic rhinitis
      throughout childhood were assessed using parental-completed questionnaires. We
      designed "environmental scores" corresponding to different indoor, green- and
      grey-related exposures (main analysis, a-priori-approach). Cohort-specific
      associations between these environmental scores and the respiratory health
      outcomes were assessed using random-effects meta-analyses. In addition, a factor
      analysis was performed based on the same exposure information used to develop the
      environmental scores (confirmatory analysis, data-driven-approach). RESULTS: A
      higher early exposure to the indoor environmental score increased the risk for
      wheezing and bronchitis within the first year of life (combined adjusted odds
      ratio: 1.20 [95% confidence interval: 1.13-1.27] and 1.28 [1.18-1.39],
      respectively). In contrast, there was an inverse association with allergic
      rhinitis between 6 and 8 years (0.85 [0.79-0.92]). There were no statistically
      significant associations for the outdoor related environmental scores in relation
      to any of the health outcomes tested. The factor analysis conducted confirmed
      these trends. CONCLUSION: Although a higher exposure to indoor related exposure
      through occupants was associated with an increased risk for wheezing and
      bronchitis within the 1st year, it might serve as a preventive mechanism against
      later childhood allergic respiratory outcomes in urbanized environments through
      enhanced shared contact with microbial agents.

PMID- 29172162
TI  - Isolation and characterization of a respirable particle fraction from residential
      house-dust.
AB  - Indoor air pollution has caused increasing concern in recent years. As we spend
      most of our lives indoors, it is crucial to understand the health effects caused
      by indoor air pollution. Household dust serve as good proxy for accessing indoor
      air pollution, especially smaller dust particles that can pass into the lungs are
      of interest. In this study we present an efficient method for the isolation of
      dust particles in the respirable size range. The respirable fraction was
      recovered from vacuum cleaner bags, separated by stepwise sieving, followed by
      characterization for size, morphology, surface area, organic content and
      elemental composition. The respirable fraction was obtained in a yield of 0.6%
      with a specific surface area of 2.5m2/g and a Mass Median Aerodynamic Diameter of
      3.73 +/- 0.15um. Aluminum and zink were the dominating metals measured in the
      dust, whereas the major mineral components were found to be silicon dioxide and
      calcium carbonate. The fraction of organic matter in the dust was measured to be
      69 +/- 1%. The organic matrix contained bacterial and fungi and a presence of
      skin fragments. We present here an efficient and fast method for the isolation of
      dust particles in the respirable size range. That is of considerable value due to
      the need for large quantities of respirable particle fractions to conduct
      toxicological studies and risk assessment work.

PMID- 29172164
TI  - Electrolysis assisted persulfate with annular iron sheet as anode for the
      enhanced degradation of 2, 4-dinitrophenol in aqueous solution.
AB  - Annular iron sheet (AIS), playing a dual role of anode electrode and source of
      activator, was combined with electrolysis technology for the activation of
      persulfate to improve the degradation of 2, 4-dinitrophenol (DNP) in aqueous
      solution. In this study, effects of current density (0-10.0mA/cm2), persulfate
      (PS) dosage (0-8.0mM), initial pH (3.0-11.0), reaction temperature (25-60 degrees
      C) and reaction time (0-30min) on COD removal of DNP in aqueous solution were
      investigated, respectively. COD removal reached its maximal value (63.4%) after
      15min treatment due to the synergistic effect in electro/AIS/PS system under the
      optimal conditions. Furthermore, comparative studies of 7 different experimental
      processes were setup. In addition, the reasonable DNP degradation pathway was
      proposed based on intermediates detected by HPLC. According to characterization
      analysis of SEM-EDS, XRD and XPS of the generated flocculation in electro/AIS/PS
      system, the possible reaction mechanism was proposed in detail. In a word, the
      electrolysis process coupled with annular iron sheet as anode activating
      persulfate technology shows a significant synergetic effect in enhancing
      degradation of DNP in aqueous solution.

PMID- 29172165
TI  - BS12-assisted flotation for the intensification of SNPs separation from CMP
      wastewater using a novel flotation column.
AB  - In view of the extremely small size, high stable dispersion and intricate
      colloidal nature of silica nanoparticles (SNPs) in chemical mechanical polishing
      (CMP) wastewater, they might not only have hazards for environment and human
      health, but also cause low separation efficiency by classical water-treatment
      processes. Thus, it would be an important challenge to develop an efficient
      flotation technology for the separation SNPs. For this propose, this paper
      firstly presented the interaction between SNPs and dodecyl dimethyl betaine
      (ambient-friendly surfactant). Secondly, a novel flotation column was developed
      for strengthening interfacial adsorption by micro-bubbles and enhancing foam
      drainage by internal of regular-decagonal hollow frustum (RHF). One vital finding
      was that the mixture of micro-bubbles and macro-bubbles was conducive to
      improving the flotation performance. Under the suitable operating conditions, the
      enrichment ratio (E) and recovery percentage (R) of SNPs could reach 30.4+/-1.5
      and 90.8+/-4.5%, respectively. The great E and R were obtained simultaneously,
      revealing a good participation of RHF in the flotation. Without a doubt, owing to
      the low chemical reagent addition and the high flotation performance, it was
      clear that our flotation has huge implications for the separation of
      nanoparticles from their wastewaters.

PMID- 29172166
TI  - Removal of volatile odorous organic compounds over NiAl mixed oxides at low
      temperature.
AB  - In this paper, a series of NiAl hydrotalcite-like compounds (HTLCs) were prepared
      by the urea-decomposition method. Removal of carbonyl sulfide (COS) and methyl
      mercaptan (CH4S) over the hydrotalcite-derived oxides (HTO) at low temperature
      was studied. The Ni3Al-HTO exhibited higher catalytic activities than Ni3Al mixed
      oxides prepared by physical mixing method (Ni3Al-PM) or impregnation/calcination
      method (Ni3Al-IC). Based on the characterization, it was found that
      desulfurization activities are closely tied to the surface acid-base properties
      of catalysts. CO2-TPD indicates that the basic characteristic of the Ni3Al-HTO is
      prominent. XPS results showed that there was a strong interaction between Ni and
      Al element on Ni3Al-HTO. The first principle calculation based on density
      function theory was applied with the aim to study the change of basic sites. The
      results showed that Ni3Al-HTO presents a half-metallic characteristic. Electron
      transfer from the Al and O atom to the Ni atom was observed, which is helpful for
      the transfer of electrons from the surface and improves the catalytic activity.
      Analysis of the DRIFT spectra suggests that sulfate species was formed by the
      action of surface basic sites, resulting in the formation of H2O on the surface.

PMID- 29172163
TI  - Patterns of gray matter atrophy in genetic frontotemporal dementia: results from
      the GENFI study.
AB  - Frontotemporal dementia (FTD) is a highly heritable condition with multiple
      genetic causes. In this study, similarities and differences of gray matter (GM)
      atrophy patterns were assessed among 3 common forms of genetic FTD (mutations in
      C9orf72, GRN, and MAPT). Participants from the Genetic FTD Initiative (GENFI)
      cohort with a suitable volumetric T1 magnetic resonance imaging scan were
      included (319): 144 nonmutation carriers, 128 presymptomatic mutation carriers,
      and 47 clinically affected mutation carriers. Cross-sectional differences in GM
      volume between noncarriers and carriers were analyzed using voxel-based
      morphometry. In the affected carriers, each genetic mutation group exhibited
      unique areas of atrophy but also a shared network involving the insula,
      orbitofrontal lobe, and anterior cingulate. Presymptomatic GM atrophy was
      observed particularly in the thalamus and cerebellum in the C9orf72 group, the
      anterior and medial temporal lobes in MAPT, and the posterior frontal and
      parietal lobes as well as striatum in GRN. Across all presymptomatic carriers,
      there were significant decreases in the anterior insula. These results suggest
      that although there are important differences in atrophy patterns for each group
      (which can be seen presymptomatically), there are also similarities (a fronto
      insula-anterior cingulate network) that help explain the clinical commonalities
      of the disease.

PMID- 29172167
TI  - Mercuric ion capturing by recoverable titanium carbide magnetic nanocomposite.
AB  - Two-dimensional metal carbides and nitrides (MXenes) have attracted increasing
      attention for application in water/wastewater treatment. The functionalization of
      MXenes to increase their stability while demonstrating high pollutant removal can
      facilitate sustainable water/wastewater treatment processes. In this study, the
      highly stable magnetic titanium carbide (Ti3C2Tx) MXene nanocomposite (MGMX
      nanocomposite) was successfully synthesized through a facile hydrothermal
      approach and was tested for aqueous-phase adsorptive removal of mercuric ions.
      The synthesized MGMX nanocomposite was studied using characteristic analyses,
      showing high stability as revealed by zeta-potential analysis and dynamic light
      scattering technique. The MGMX nanocomposite presented excellent Hg(II) removal
      in a wide range of pH conditions, and an exceptional maximum experimental Hg(II)
      uptake capacity of 1128.41mgg-1 was observed. The adsorption behavior was
      investigated using the Redlich-Peterson adsorption isotherm, pseudo second-order
      kinetics, and thermodynamics models. In the adsorption/desorption investigation,
      the MGMX nanocomposite was reusable for up to five cycles of
      adsorption/desorption. The stability, hydrophilic nature, available adsorptive
      surfaces, and easy separation after reaction make the MGMX nanocomposite an
      efficient sorbent for the removal of toxic Hg(II) for water purification.

PMID- 29172168
TI  - Electrospun AOPAN/RC blend nanofiber membrane for efficient removal of heavy
      metal ions from water.
AB  - In this study, an innovative nano-material was prepared, which was ultilized to
      removal of heavy metal ions from wastewater. Polyacrylonitrile/cellulose acetate
      (PAN/CA) composite nanofibrous membranes were generated by the electronspinning
      technique first, and then amidoxime ployarcylonitrile/regenerate cellulose
      (AOPAN/RC) composite nanofibrous membranes were prepared by combining hydrolysis
      and amidoximation modification. The modification of composite nanofibers
      (AOPAN/RC) were consequently used in heavy metal ions adsorption. The
      characterizations of various different nanofibers were analyzed using scanning
      electron microscopy, Fourier transform infrared spectroscopy, surface area and
      pore size distribution analyzer and energy dispersive X-ray spectroscopy.
      Meantime, the adsorption equilibrium studies were studied. In addition, the
      saturation adsorption amount of nanofibrous membranes (at 25 degrees C) for
      Fe(III), Cu(II) and Cd(II) of 7.47, 4.26 and 1.13mmolg-1, respectively. The
      effects of pH value of solution, adsorption time and ions concentration on
      adsorption capacity were also investigated. Furthermore, the composite
      nanofibrous membranes after five times consecutive adsorption and desorption
      tests, the desorption rate of the Fe(III), Cu(II) and Cd(II) mental ions
      maintained more than 80% of their first desorption rate, AOPAN/RC composite
      nanofibrous reflected excellent resuability.

PMID- 29172169
TI  - Magnetic multi-metal co-doped magnesium ferrite nanoparticles: An efficient
      visible light-assisted heterogeneous Fenton-like catalyst synthesized from
      saprolite laterite ore.
AB  - Magnetic nanoparticles of multi-metal co-doped magnesium ferrite (MgFe2O4) were
      synthesized from saprolite laterite ore by a hydrothermal method, and firstly
      proposed as a heterogeneous photon-Fenton-like catalyst for degradation of
      Rhodamine B (RhB). The factors that influence the degradation reaction including
      pH value, the concentration of H2O2 and the amount of catalyst, were
      systematically investigated. The doped MgFe2O4 exhibited a degradation efficiency
      up to 96.8%, and the chemical oxygen demand (COD) and total organic carbon (TOC)
      removal efficiencies about 85.6% and 68.3%, respectively, under visible light
      illumination for 180min. The high activity is mainly attributed to the high
      specific surface area of the catalyst and the synergistic interaction between
      photo-catalytic oxidation and Fenton-like oxidation. Moreover, the catalyst also
      showed good stability and recycling performance for degrading RhB. After five
      consecutive degradation cycles, the activity decayed no more than 10%. Compared
      to other catalysts prepared from pure chemical agents, the multi-metal co-doped
      MgFe2O4 is more competitive due to its high activity, good stability, ease of
      recollection, and especially the use of saprolite laterite ore as precursor. This
      work may provide a new avenue to synthesize efficient ferrite catalysts for
      degrading organic pollutants in wastewater by using natural minerals.

PMID- 29172170
TI  - A pure shift experiment with increased sensitivity and superior performance for
      strongly coupled systems.
AB  - Motivated by the persisting need for enhanced resolution in solution state NMR
      spectra, pure shift techniques such as Zangger-Sterk decoupling have recently
      attracted widespread interest. These techniques for homonuclear decoupling offer
      enhanced resolution in one- and multidimensional proton detected experiments by
      simplifying multiplet structures. In this work, a modification to the popular
      Zangger-Sterk technique PEPSIE (Perfect Echo Pure Shift Improved Experiment) is
      presented, which decouples pairs of spins even if they share the same volume
      element. This in turn can drastically improve the sensitivity, as compared to
      classical Zangger-Sterk decoupling, as larger volume elements can be used to
      collect the detected signal. Most interestingly, even in the presence of moderate
      strong coupling, the PEPSIE experiment produces clean and widely artifact free
      spectra. In order to better understand this - to us initially - surprising
      behaviour we performed analyses using numerical simulations and derived an
      (approximate) analytical solution from density matrix formalism. We show that
      this experiment is particularly suitable to study samples with strong signal
      clustering, a situation which can render classic Zangger-Sterk decoupling
      inefficient.

PMID- 29172171
TI  - Trastuzumab for metastatic breast cancer: Real world outcomes from an Australian
      whole-of-population cohort (2001-2016).
AB  - PURPOSE: Outcomes for patients treated in clinical trials may not reflect the
      experience in routine clinical care. We aim to describe the real-world treatment
      patterns and overall survival (OS) for women receiving trastuzumab for metastatic
      breast cancer (MBC). METHODS: Retrospective, whole-of-population cohort study
      using demographic, dispensing, and medical services data for women in the
      Herceptin Program for HER2+MBC. We estimated time on trastuzumab and OS from
      first dispensing of trastuzumab for MBC and rates of cardiac monitoring prior to
      and during treatment. We stratified outcomes by two groups based on year of
      initiation: 2001-2008 and 2009-2015. We benchmarked outcomes to two key
      trastuzumab clinical trials: H0648g (median OS 25 months) and CLEOPATRA (control
      group median OS 41 months). RESULTS: Median age of the 5899 women at first
      trastuzumab dispensing was 57 years (interquartile range [IQR]: 48-66). Median
      time on trastuzumab increased from 15 months (7-33) in Group One to 18 months (8
      42) in Group Two. Median OS increased from 27 months (12-57) in Group One to 38
      months (16-83) in Group Two. Rates of cardiac monitoring increased at baseline
      (52%-76%), and on-treatment (47%-67%), in Group One and Two, respectively.
      CONCLUSIONS: OS, duration of trastuzumab, and frequency of cardiac monitoring
      increased over the study period. Outcomes for trastuzumab in this heterogeneous
      real world population were reassuringly comparable to those from clinical trials,
      with the median OS > 3 years in Group Two and 25% of patients living 7 years or
      longer.

PMID- 29172172
TI  - Visualization of old bruises in children: Use of violet light to record long-term
      bruises.
AB  - When a child consultation center evaluates abused children, evidence of the abuse
      must be documented. Children who have suffered physical abuse often have bruises,
      which cannot be confirmed by visualization when the bruise has healed. In
      forensics, a method to confirm an old bruise by ultraviolet radiation is
      possible. However, long-term ultraviolet exposure can be harmful. In this study,
      we observed 15 bruises on healthy volunteer children using four kinds of light
      sources, including ultraviolet radiation, over time. The violet light source
      enabled observation of a bruise for a longer time than ultraviolet radiation.
      Although other studies have shown that violet light is superior for enhancing
      bruises, this is the first report to evaluate data concerning the ability to
      identify bruises over time in living children. These results might help to
      identify evidence of past violence suffered by children.

PMID- 29172173
TI  - Specific IgE levels in pericardial and cerebrospinal fluids in forensic casework:
      The presence of additional molecules for sudden cardiac death diagnosis.

PMID- 29172174
TI  - Deficit of supramodal executive control of attention in schizophrenia.
AB  - Although a deficit in executive control of attention is one of the hallmarks in
      schizophrenia that has significant impact on everyday functioning due to its
      relationship with thought processing, whether this deficit occurs across
      modalities, i.e., is supramodal, remains unclear. To investigate the supramodal
      mechanism in SZ, we examined cross-modal correlations between visual and auditory
      executive control of attention in a group of patients with schizophrenia (SZ, n =
      55) compared to neurotypical controls (NC, n = 55). While the executive control
      effects were significantly correlated between the two modalities in the NC group,
      these effects were not correlated in the SZ group, with a significant group
      difference in the correlation. Further, the inconsistency and magnitude of the
      cross-modal executive control effects were significantly larger in the SZ group
      compared to the NC group. Together, these results suggest that there is a
      disruption of a common supramodal executive control mechanism in patients with
      schizophrenia, which may be related to the thought processing disorder
      characterizing the disorder.

PMID- 29172176
TI  - ATP-sensitive and maxi potassium channels regulate BRL 37344-induced tocolysis in
      buffaloes-an in vitro study.
AB  - Cellular coupling of beta3-adrenoceptors (beta3-ADR) to potassium channels in
      myometrium is largely unknown. In vitro study was undertaken to unravel the
      presence of beta3-adrenergic receptors (ADR) and the role of K+-channels in
      mediating beta3-ADR-induced relaxation in isolated myometrial strips from cyclic
      non-pregnant water buffaloes. Isometric tension was recorded in isolated
      myometrial strips using data acquisition system based physiograph. Compared to SR
      59230A, BRL 37344 was found to be more potent in inducing beta3-dependent
      myometrial relaxation which was significantly (p < 0.05) inhibited in the
      presence of beta3 antagonist, SAR 150640. The immunoreactive protein to beta3-ADR
      was also detected in membrane fraction of myometrial protein. Further, incubation
      with BRL 37344 (10 MUM) significantly (p < 0.05) increased c-AMP accumulation
      (37.58 +/- 9.52 pmol/mg protein; n = 4) in the myometrial strips compared to
      basal c-AMP level (16.85 +/- 3.87 pmol/mg protein; n = 4). The concentration
      response curves (CRC) of BRL 37344 were significantly (p < 0.05) shifted towards
      right in the presence of KATP channels specific blocker, glibenclamide (10 MUM)
      and maxi K+-channels (BKCa) specific blocker, iberiotoxin (100 nM), with decrease
      in both efficacy and potency as compared to control. However, 4-aminopyridine (4
      AP), a specific blocker of the voltage gated K+-channels (Kv), failed to alter
      the CRC of BRL 37344. Existence of immunoreactive protein to Kir6.1, alpha
      subunit of BKCa and Kv1.1 channels were also detected in the membrane fraction of
      myometrial protein. Based on the above findings, it can be concluded that BRL
      37344 is a potent stimulator of beta3-adrenoceptors in buffalo myometrium and
      besides mediating their effect through rise in c-AMP, they are coupled to KATP
      and BKCa channels in inducing tocolytic effects.

PMID- 29172175
TI  - A predictive threshold value for the diagnosis of early pregnancy in cows using
      interferon-stimulated genes in granulocytes.
AB  - Interferon tau plays an important role in establishing bovine pregnancy.
      Interferon-stimulated genes (ISGs) have been examined to identify a suitable
      indicator for the diagnosis of early gestation in cows. Although ISGs can be
      specifically detected in peripheral white blood cells during early gestation, its
      reliability remains to be validated. In the current study, a predictive threshold
      level of ISGs to determine pregnancy in cows during Days 20-22 of gestation was
      verified by analyzing the expression of ISGs in granulocytes and peripheral blood
      leucocytes (a total of 57 cows were used, 28 of which were pregnant and 29 were
      non-pregnant). Four genes, interferon-stimulated gene 15 ubiquitin-like modifier
      (ISG15), MX dynamin like GTPase (MX) 1, MX2, and 2'-5'-oligoadenylate synthetase
      1 (OAS1), were analyzed via quantitative RT-PCR and a receiver operating
      characteristic (ROC) curve was produced to visualize diagnostic accuracy
      measures. The expression values of the four ISGs during the estrous cycle (100
      collection points from 65 cattle) were used to determine a pregnancy prediction
      cutoff value. Pregnancy status was determined using these cutoff values and then
      confirmed by ultrasonography. ROC analysis was then applied to confirm the
      accuracy of the pregnancy statuses (positive and negative) statistically. The
      statistical evaluation of the diagnostic accuracy measurements suggested that the
      average values of ISG15 and MX2 in granulocytes were reliable indicators of
      pregnancy within the three weeks after insemination with 80% accuracy. Average
      ISG15 and MX2 levels during the estrous cycle were more reliable biomarkers for
      the prediction of gestation. They predicted negative and positive pregnancies
      efficiently within three weeks after artificial insemination.

PMID- 29172177
TI  - Lupeol supplementation improves the developmental competence of bovine embryos in
      vitro.
AB  - Lupeol is a triterpene with various pharmacological properties. This study
      investigated the effect of lupeol on the in vitro development of bovine embryos.
      Oocytes (270 per group, 1620 in total) obtained from slaughterhouse-derived
      ovaries were matured and fertilized in vitro and then cultured for 8 days in a
      humidified atmosphere of 5% CO2 in air at 38.5  degrees C. The in vitro
      maturation medium was supplemented with 0.5, 1.0, 2.0, 3.0, and 4.0 MUM lupeol.
      Treatment with 2.0 MUM lupeol significantly (P < 0.05) improved blastocyst
      development. Hoechst 33342 staining and terminal deoxynucleotidyl transferase
      dUTP nick-end labeling showed that treatment with 2.0 MUM lupeol improved
      blastocyst quality by increasing the total cell number and reducing the apoptotic
      cell number. Confocal microscopy confirmed that treatment with 2.0 MUM lupeol
      significantly (P < 0.05) reduced the level of 8-oxoguanine, an indicator of
      reactive oxygen species. Lupeol treatment also significantly attenuated protein
      expression of nuclear factor-kappa B subunit 1 (NFKB1), cyclooxygenase (COX) 2,
      and CASP3. Real-time PCR analysis of nitric oxide synthase 2, NFKB1, COX2, CASP3,
      and BCL2-associated X protein supported the immunofluorescence data. In
      conclusion, lupeol is a potent antioxidant that improves bovine embryo
      development in vitro.

PMID- 29172178
TI  - A 10-year follow-up study of violent victimization in first episode psychosis:
      Risk and protective factors.
AB  - Violent victimization in persons with severe mental illness has long-term adverse
      consequences. Little is known about the long-term prevalence of victimization in
      first episode psychosis, or about factors affecting victimization throughout the
      course of illness. To assess the prevalence of violent victimization during a 10
      year follow-up period in a group of first episode psychosis (FEP) patients, and
      to identify early predictors and risk factors for victimization. A prospective
      design was used with comprehensive assessments of violent victimization,
      treatment variables and functioning at baseline and during 10-year follow-up. A
      clinical epidemiological sample of FEP patients (n = 298) was studied. FEP
      patients in our study were at a 3.5 times greater risk of victimization as
      compared to the normal population. During the 10-year follow-up period, 23% of
      subjects fell victim to one or more violent assaults. Victimized patients were
      younger and reported less occupational activity. At 10-year follow-up,
      victimization was associated with more concomitant drug use, alcohol misuse and
      violent behavior, but not with a worse clinical or functional outcome. Treatment
      programs should focus on risk factors for victimization and develop behavioral
      alternatives to mitigate risk in FEP patients.

PMID- 29172179
TI  - Higher participation in physical activity is associated with less use of
      inpatient mental health services: A cross-sectional study.
AB  - There is a stark disparity in the physical health of people with mental illness
      compared to those without mental illness, resulting in shorter life expectancy
      and increased rates of preventable deaths. Physical activity has previously been
      shown to have a positive impact on various markers of mental health and has been
      linked with a reduction in hospital admissions for those with chronic physical
      illness. The purpose of this study was to investigate whether there is a
      relationship between physical activity and the number of days spent admitted to
      acute inpatient mental health wards in people with enduring mental illness.
      Eighty participants from four acute mental health wards in Oxfordshire, UK were
      included. Subjective and objective measurements of physical activity levels were
      collected alongside the amount of days spent admitted on acute mental health
      wards over the year previous. Participants who recorded higher levels of physical
      activity, both subjectively and objectively, were found to have spent less time
      admitted to acute mental health services. With a significant negative correlation
      found, future research should aim to investigate any causative link between
      physical activity and mental health admission.

PMID- 29172180
TI  - Microsatellite Alterations and Protein Expression of 5 Major Tumor Suppressor
      Genes in Gastric Adenocarcinomas.
AB  - PURPOSE: In gastric adenocarcinoma (GC), the major tumor suppressor genes (TSGs)
      such as p16, PTEN, Rb, E-cadherin, and p53, may play important roles in various
      regulatory pathways and in tumor suppression. This study evaluated the loss of
      heterozygosity (LOH) of microsatellite and protein expression of 5 TSGs and the
      results were examined for their correlation with clinicopathological factors.
      METHODS: LOH analysis was carried out using polymerase chain reactions with 15
      polymorphic microsatellite markers of 5 chromosomes containing TSGs in 100
      surgically resected tumors. Protein expression was evaluated by
      immunohistochemistry (IHC). RESULTS: LOH was detected in 83% of GCs. LOH of 9p21,
      10q23, 13q14, 16q22, and 17p13 were detected in 26%, 31%, 24%, 22%, and 35% of
      cases, respectively. Protein expression of p16, PTEN, Rb, E-cadherin, and p53
      were found to be 31%, 39%, 28%, 32%, and 46% of cases. Advanced GCs showed
      significantly higher rates of 17p13 LOH and p53 expression. 9p21 LOH and E
      cadherin IHC were correlated with higher tumor grade. Lymph node metastasis was
      correlated with the LOH of 9p21, 16q22, and 17p13 and IHC of the Rb and p53. A
      higher stage was correlated with 10q23 and 17p13 in LOH and p53 for IHC.
      CONCLUSION: These results suggest that LOH and protein expression of various TSGs
      are important in carcinogenesis and tumor invasion. Additionally, LOH and IHC may
      be useful clinical indicators for determining the prognosis of patients with GCs.
      In particular, the 17p13 LOH and p53 for IHC can be applied as simple evaluations
      in the clinic.

PMID- 29172181
TI  - Efficient removal of Cr(VI) from water by quaternized chitin/branched
      polyethylenimine biosorbent with hierarchical pore structure.
AB  - A novel chitin-based biosorbent (QCP) was synthesized by cross-linking
      quaternized chitin and branched polyethylenimine with the aid of epichlorohydrin
      for efficient removal of Cr(VI) from water. Because it possessed both quaternary
      ammonium groups and amino groups as well as the hierarchical pore structure, QCP
      presented a maximum adsorption capacity of 387.7 mg/g according to the Langmuir
      isotherm at 25  degrees C. The biosorption of QCP achieved the equilibrium within
      40 min and followed the pseudo-second-order kinetic model. QCP worked well even
      in the solution with high pH and high content of competing anions and, it
      exhibited an excellent reusability. The main Cr(VI) uptake mechanism was
      confirmed to be electrostatic attractions between Cr(VI) anions and quaternary
      ammonium groups as well as the protonated amino groups, and followed by partial
      reduction of Cr(VI) to Cr(III) by amines and hydroxyls. This work may provide a
      potential for Cr(VI) removal by chitin-based biosorbents.

PMID- 29172182
TI  - Enhanced nitrogen and phosphorus removal from domestic wastewater via algae
      assisted sequencing batch biofilm reactor.
AB  - This study proposed a potential strategy for enhancement of nutrients removal
      from domestic wastewater by adding algae to sequencing batch biofilm reactor
      (SBBR) to form a novel algal-bacterial symbiosis (ABS) system. Results indicated
      that the algae-assisted SBBR increased the total nitrogen and phosphorus removal
      efficiencies from 38.5% to 65.8%, and from 31.9% to 89.3%, respectively. The
      carriers fixed at the top of the reactor were favorable for both formation of ABS
      system and algae enrichment. The chlorophyll-a increased to 3.59 mg/g at stable
      stage, which was 4.07 times higher than that in suspension. Moreover, the bio
      carrier replacement and sludge discharge were independent, indicating that the
      sludge and algae retention time could be separated. The mechanisms analysis
      suggested that the enhanced nitrogen and phosphorus mainly attributed to the
      enrichment of both algae biomass and total biomass in biofilm. This study
      highlights the significance of developing ABS system for wastewater treatment.

PMID- 29172183
TI  - Enzymatic hydrolysis at high dry matter content: The influence of the substrates'
      physical properties and of loading strategies on mixing and energetic
      consumption.
AB  - The present work investigates the impact of the physical properties and loading
      strategies of wheat straw and miscanthus on enzymatic hydrolysis at high DM
      concentration. Three parameters have been chosen to evaluate the enzymatic
      hydrolysis performance: (i) the mixing time, (ii) the energetic mixing
      consumption and (iii) the glucose concentration. It was demonstrated that the
      hydrolysis of miscanthus is easy to perform and has low viscosity. On the
      contrary, the higher porosity grade of wheat straw than miscanthus (73% against
      52%) contributed to have a very high viscosity at 20% w/w DM. The development of
      a fed-batch strategy allowed the reduction of viscosity inducing the energetic
      consumption lowering from 30 kJ to 10 kJ. It has been also proven that the
      miscanthus addition in wheat straw achieved to decrease mixing energy consumption
      at 5-8 kJ, when it represented more than 30% of the total mass of the reaction
      medium.

PMID- 29172184
TI  - [Phenomenon of Perceived Duration in the Subjective Present].
AB  - Among phenomena involving the subjective present, duration perception is
      especially worth discussing from the viewpoints of psychophysics, cognitive
      neuroscience, and computational modeling of underlying mechanisms. First, several
      situations in which moving visual stimuli appear to last longer are reported.
      Second, the phenomenon of illusory time compression, which occurs in a moving
      stimulus after prolonged observation of another stimulus moving at a faster
      speed, is described. Third, how an attended visual stimulus appears to last
      longer and how a stimulus appears to last for a shorter duration when attention
      is directed away are explained. Finally, possible underlying mechanisms in
      relation to the stages of hierarchical visual information processing are
      discussed.

PMID- 29172185
TI  - [Dynamic Attending Binds Time and Rhythm Perception].
AB  - Relations between time and rhythm perception are discussed in this review of
      psychophysical research relevant to the multiple-look effect and dynamic
      attending theory. Discrimination of two neighboring intervals that are marked by
      three successive sounds is improved when the presentation of the first (standard,
      S) interval is repeated before that of the second (comparison, C), as SSSSC. This
      improvement in sensitivity, called the multiple-look effect, occurs because
      listeners (1) perceive regular rhythm during the repetition of the standard
      interval, (2) predict the timing of subsequent sounds, and (3) detect sounds that
      are deviated from the predicted timing. The dynamic-attending theory attributes
      such predictions to the entrainment of attentional rhythms. An endogenous
      attentional rhythm is synchronized with the periodic succession of sounds marking
      the repeated standard. The standard and the comparison are discriminated on the
      basis of whether the ending marker of the comparison appears at the peak of the
      entrained attentional rhythm. This theory is compatible with the findings of
      recent neurophysiological studies that relate temporal prediction to neural
      oscillations.

PMID- 29172186
TI  - [Neural Basis for Producing Temporal Order].
AB  - It has been proposed that a position in time can be discriminated in two ways.
      First, each position is either past, present, or future (A series). Second, each
      position is either before or after another (B series). In this review, we aim to
      infer how the two series are represented in the brain on the basis of findings
      from clinical, neurophysiological, and neuroimaging studies. We suggest that the
      precuneus and posterior cingulate cortex are critically involved in the A series.
      In the B series, we suggest that a group of events are represented in space
      around the intraparietal cortex and are combined with the temporal directional
      cue provided by the motion signals in the left temporo-parietal junction. We also
      review a report that states that the B series is affected by alpha rhythm, the
      source of which is located in the precuneus. Taken together, we suggest that the
      precuneus and the regions adjacent to it play key roles in representing the A and
      B series.

PMID- 29172187
TI  - [Neural Mechanisms of Temporal Monitoring and Prediction].
AB  - When waiting for a traffic light or dancing to a musical beat, we unconsciously
      keep track of elapsed time and precisely predict the timing of forthcoming
      sensory events. Temporal monitoring and prediction are integral to our daily
      life, and are regulated by neuronal processes through multiple global networks
      involving the frontoparietal cortices, the basal ganglia and the cerebellum.
      These processes are also known to be influenced by a variety of internal state
      and neuromodulators. Here, we review recent advance of research in the field.

PMID- 29172188
TI  - [Posterior Cingulate Cascading Delay Model for Timing Behavior].
AB  - We present a novel model for timing behavior. This model is based on the firing
      property of neurons in the superficial layers of the posterior cingulate granular
      retrosplenial cortex (GRS) and does not require a unit-time clock. Suppose that
      event B occurs N seconds after event A and triggers behavior C. By our
      behavioral, physiological and anatomical experiments, we found the following
      facts. 1) Thalamic input carrying sensory information, A, is provided to the
      superficial layers of the GRS and delayed by the lateral cascading connection
      within the layers. 2) Hippocampal input (recall information, B) is provided to
      the deep layers of the GRS. 3) The GRS neurons show timing behavior that is
      dependent on the trial cycle. 4) Lesioning the GRS impaired the acquisition of
      trace fear memory and the production of fear-induced freezing behavior, C. Thus
      we would propose that neural circuits in the GRS play a crucial role in the
      animal behaviors requiring time discrimination. The question of whether Hebbian
      learning occurs at the convergent neurons that integrates thalamic and
      hippocampal information remains unanswered.

PMID- 29172189
TI  - [Representation of Time by Hippocampal Neurons].
AB  - The hippocampus is involved in episodic memories of events including time and
      space. Many studies have focused on the neuronal processing mechanisms underlying
      spatial cognition and representation in the hippocampus; however, the time
      related aspects of memories have only recently become the focus of research. In
      this review, we first introduce recent reports demonstrating the importance of
      the hippocampus in the perception of time and then present the hippocampal
      neuronal dynamics for the representation of time, revealed by large-scale
      neuronal recording techniques.

PMID- 29172190
TI  - [Neural Mechanisms That Facilitate Adaptive Behavior Based on Acquired Stimulus
      Outcome Information].
AB  - In response to changing internal and external situations, we always need to adapt
      our behavior based on previous experiences, particularly, acquired stimulus
      outcome information. The orbitofrontal cortex (OFC), a prefrontal cortical
      region, is critical for this type of decision-making. The current understanding
      of the fundamental functions of the OFC has been reviewed by introducing, as an
      example, how the OFC contributes to the processing of uncertain rewards.
      Furthermore, the importance of revealing context and temporally specific causal
      roles of neural circuits including the OFC in decision-making, as well as the
      techniques to achieve the goal, have been discussed.

PMID- 29172191
TI  - [Development of Temporal Systems in Child Language from the Viewpoint of
      Universality and Variation in the Encoding of Time in Human Languages].
AB  - This study explores how time is conceptualized and linguistically encoded by
      human beings. In order to examine how the temporal systems develop in child
      language, we have conducted investigations on how their development relates to
      universal and idiosyncratic aspects of the temporal systems of the languages of
      the world. We have found that both the uniformity and the variation across
      languages in the development of tense-aspect marking in child language are
      attributable to the interaction of three aspects of the typological pattern of
      the target language: morphology, the presence or absence of optionality of tense
      aspect marking, and the inventory of tense-aspect markers.

PMID- 29172192
TI  - [Neuropsychology of the Psychological Present].
AB  - The psychological present is a diverse psychological phenomenon, including the
      perception and evaluation of time, which has been studied from different
      perspectives. The experience of the psychological present is known to differ
      according to psychological state and cognitive processes, such as attention.
      Neuropsychological studies focused on brain-damaged patients have explored
      several aspects of the present, but few studies have examined the subjective
      aspect of the phenomenon. In this article, we focus on the subjective aspect of
      the present in brain-damaged patients and propose that the psychological present
      is maintained by several brain regions through the integration of multiple
      information sources.

PMID- 29172193
TI  - [Hypersensitivity as Extraordinary High Temporal Processing in Individuals with
      Autism-Spectrum Disorders].
AB  - Most individuals with autism-spectrum disorders have
      hypersensitivity/hyposensitivity to various types of sensory stimuli. Although
      several hypotheses such as higher sensitivity to stimuli, alterations in brain
      structure and function, and dysfunction of inhibitory systems at the molecular
      level have been suggested, there is no convincing evidence. We found that
      individuals with high temporal resolution tended to have strong hypersensitivity
      to sensory stimuli and vice versa. In addition, we focused on a case with
      extraordinarily high temporal resolution across the tactile, auditory, and audio
      tactile domains. We believe that studying such an extreme case of temporal
      processing could facilitate an understanding of the neural basis of time
      perception.

PMID- 29172194
TI  - [Mental Space Navigation and Mental Time Travel].
AB  - We examined patients with mental space navigation or mental time travel disorder
      to identify regions in the brain that may play a critical role in mental time
      travel in terms of clinical neuropsychology. These regions included the precneus,
      posterior cingulate gyrus, retrosplenial cortex, and hippocampus, as well as the
      orbitofrontal cortex: the anterior and posterior medial areas were both shown to
      be important in this process. Further studies are required to define whether
      these form a network for mental time travel.

PMID- 29172195
TI  - [Neural Mechanisms Underlying the Processing of Temporal Information in Episodic
      Memory and Its Disturbance].
AB  - Episodic memory is defined as memory for personally experienced events, and
      includes memory content and contextual information of time and space. Previous
      neuroimaging and neuropsychological studies have demonstrated three possible
      roles of the temporal context in episodic memory. First, temporal information
      contributes to the arrangement of temporal order for sequential events in
      episodic memory, and this process is involved in the lateral prefrontal cortex.
      The second possible role of temporal information in episodic memory is the
      segregation between memories of multiple events, which are segregated by cues of
      different time information. The role of segregation is associated with the
      orbitofrontal regions including the orbitofrontal cortex and basal forebrain
      region. Third, temporal information in episodic memory plays an important role in
      the integration of multiple components into a coherent episodic memory, in which
      episodic components in the different modalities are combined by temporal
      information as an index. The role of integration is mediated by the medial
      temporal lobe including the hippocampus and parahippocampal gyrus. Thus, temporal
      information in episodic memory could be represented in multiple stages, which are
      involved in a network of the lateral prefrontal, orbitofrontal, and medial
      temporal lobe regions.

PMID- 29172196
TI  - [Memory of Past Events and Mental Time Travel in Apes].
AB  - Mental time travel refers to the ability to recall a past event and imagine the
      future. Some researchers claim that this ability is unique to humans, while
      others argue that nonhuman animals also possess this ability. A study on apes by
      using eye-tracking revealed that chimpanzees and bonobos can remember a single
      event for 24 hours, suggesting that they possess at least some elements of mental
      time travel.

PMID- 29172197
TI  - [Voxel-Based Morphometry and Social Cognitive Function in Parkinson's Disease].
AB  - In recent years, voxel-based morphometry (VBM) has been increasingly used to
      investigate local brain structures in Parkinson's disease (PD). Compared to
      healthy participants, PD patients tend to show reduced brain volume in limbic and
      paralimbic areas in early disease stages, while the neocortical areas, such as
      the temporal and frontal cortices, are affected in advanced patients. Moreover,
      there are many studies showing correlation between cognitive performance and
      local brain volume. In the last decade, emotional and social cognitive function,
      such as facial emotion recognition, emotional decision-making, and theory of
      mind, have been the target of VBM analysis in PD. These studies facilitate
      understanding of the nature of communication and behavioral disorders that some
      PD patients display. However, there are discrepancies in VBM results between
      studies. Future studies need to employ larger sample sizes and combined analysis
      of brain perfusion or network connectivity in order to confirm brain structural
      changes and their effects on social cognitive function in PD patients.

PMID- 29172198
TI  - [Anti-MOG Antibody Associated Diseases].
AB  - The anti-MOG antibody is an autoantibody that induces inflammatory demyelinating
      lesions in the central nervous system in diseases such as optic neuritis,
      encephalitis, and myelitis. The recent development of a cell-based assay that can
      detect specific autoantibodies, which recognize conformational epitopes of
      membrane proteins, revealed the clinical features of diseases associated with the
      anti-MOG antibody. Because the disease spectrum of anti-MOG antibody-associated
      diseases is different from that of conventional demyelinating diseases, a new
      disease classification would be established in the near future.

PMID- 29172199
TI  - [Clinical Features of Very Elderly Patients Aged 90 Years or Above with Acute
      Ischemic Stroke: A Study by Using Diffusion Weighted Brain Magnetic Resonance
      Imaging].
AB  - We investigated the diffusion weighted magnetic resonance imaging (DWI) features
      of 76 very elderly patients aged 90 years or above with acute ischemic stroke.
      Stroke subtypes were classified into five types according to the Trial of Org
      10172 in Acute Stroke Treatment (TOAST) and the Japanese Stroke Databank. The
      incidence rates of atherothrombotic brain infarction (ATBI), atherothrombotic
      brain embolism (ATBE), lacunar infarction (LI), cardiogenic brain embolism (CBE)
      and undetermined type of brain infarction (UTBI) were 2.6%, 17.1%, 10.5%, 50.0%
      and 19.8%, respectively. We estimated that the incidence of acute ischemic stroke
      in women was 3.5-fold higher than that in men. This is likely because survival
      rate of females is higher than that of males in populations aged 90 years or
      above. The prevalence of atrial fibrillation (AF) was 46.1% in patients with
      brain infarctions, and 92.1% in patients with CBE. The frequency of multiple
      infarctions is 52.6% and that of single infarction is 47.4%. In DWI of lesions,
      the frequencies of territorial infarction in the cerebral hemisphere, borderzone
      infarction, and vertebrobasilar infarction were 85.5%, 13.2% and 17.1%,
      respectively. The frequencies of massive territorial infarction and cerebellar
      infarction were 23.7% and 13.2%, respectively. With regard to the relationship
      between DWI lesion topography and stroke subtypes, superficial infarctions in the
      cerebral hemisphere were seen in patients with ATBE, CBE and UTBI. Single
      infarctions deep in the cerebral hemisphere were seen in all patients with any of
      the five stroke subtypes. Massive territorial infarctions with infarctions in
      other sites of the cerebral hemisphere or vertebrobasilar region were seen only
      in patients with CBE, and single pontine infarction was seen only in patients
      with LI. (Received November 19, 2015; Accepted July 3, 2017; Published November
      1, 2017).

PMID- 29172200
TI  - [Outcome of Coil Embolization for Subarachnoid Hemorrhage Accompanied with
      Intracerebral Hematoma].
AB  - OBJECT: Aneurysmal subarachnoid hemorrhage(SAH)associated with intracerebral
      hematoma(ICH)typically has a poor outcome. SAH with ICH tends to have a worse
      prognosis than SAH alone. The aim of the present study was to evaluate whether
      coil embolization during endovascular surgery with ventricle drainage and without
      ICH evacuation is an appropriate treatment. METHODS: A retrospective review was
      conducted between March 2012 and May 2015. Thirteen patients with SAH with ICH
      who underwent coil embolization were retrospectively analyzed. Modified Rankin
      Scale(mRS)scores were compared for postoperative clinical outcomes of different
      hematoma locations. RESULTS: All ruptured aneurysms in the present series of
      patients were treated using endovascular surgery. Six patients underwent
      additional ventricle drainage. Only one patient underwent craniotomy for
      evacuation of the hematoma following coil embolization. Despite ten out of
      thirteen patients(76.9%)having a preoperative SAH clinical grade, as evaluated
      using the World Federation of Neurosurgical Societies grading system of IV or V,
      six(46.2%)patients had a favorable outcome(mRS=0-2). CONCLUSIONS: Coil
      embolization for ruptured aneurysms, especially those located in the frontal
      lobe, with ICH and without cerebral herniation may be a feasible alternative and
      less invasive treatment.

PMID- 29172201
TI  - [Effect of Platelet Concentrate Transfusion on Prognosis of Patients with
      Intracerebral Hemorrhage Treated with Anti-Platelet Agents].
AB  - BACKGROUND: A recent randomized control study(the PATCH trial)found no beneficial
      effect of platelet concentrate(PC)transfusion on the prognosis of patients with
      intracerebral hemorrhage(ICH)treated with anti-platelet agents(APAs). However,
      the trial excluded surgical cases. In this study, we examined the effect of PC on
      ICH, including patients who received surgical treatment. METHOD: A retrospective
      cohort analysis was performed in 23(11 males, 12 females)of 35 patients diagnosed
      with ICH and treated with APAs between January 2010 and December 2015 at the
      Department of Neurosurgery, Yamaguchi University Hospital. Twelve patients were
      excluded due to the use of anticoagulants or replenishment of coagulation
      factors. RESULTS: PC transfusion was administered in 12 cases(PC group)but not
      administered in 11(non-PC group). Conservative therapy at admission was used in 7
      and 9 cases in the PC and non-PC groups, respectively, and none of these cases
      showed hematoma enlargement during conservative therapy. Surgical treatment was
      performed in 6 and 2 patients in the PC and non-PC groups, respectively, and
      hematoma enlargement occurred postoperatively in one patient in each group.
      Outcomes at 3 months after onset showed no significant difference between the
      groups(mRS 0-3:6 vs. 5 cases, p=0.34). Patients who received PC had no serious
      adverse events during hospitalization. CONCLUSION: In this study, surgery after
      PC transfusion was performed without any problems. There was no difference in
      prognosis between patients who did and did not receive PC. These results suggest
      that surgery can be performed safely after PC transfusion.

PMID- 29172202
TI  - [Bilateral Pallidotomy for Tardive Dystonia:A Case Report].
AB  - Tardive dystonia is a movement disorder related to the use of dopamine-receptor
      blocking drugs. Several reports have shown that deep brain stimulation of the
      globus pallidus internus(GPi-DBS)is effective in treating tardive dystonia.
      However, a few reports demonstrated the efficacy of ablation of the
      GPi(pallidotomy). We herein report a case of tardive dystonia successfully
      treated with bilateral pallidotomy. A 32-year-old man developed severe tardive
      dystonia 10 years after the chronic use of antipsychotic drugs. Withdrawal of the
      drugs and botulinum toxin injections were ineffective. The patient underwent
      bilateral pallidotomy for tardive dystonia because of rejection of the implanted
      DBS devices. Significant improvement was observed, with a 95% decrease in the
      Burke-Fahn-Marsden Dystonia Rating Scale(BFMDRS)movement score, and no severe
      adverse events occurred. Symptomatic relief persisted for nine months.
      Pallidotomy is a feasible and efficacious procedure for tardive dystonia
      treatment without the use of hardware implantations.

PMID- 29172203
TI  - [Factor Xa Inhibitor for the Treatment of Cerebral Venous Thrombosis with
      Intracerebral Hemorrhage during Anticoagulation Therapy:A Case Report].
AB  - A 46-year-old man presented with headache, right hemiparesis, and motor aphasia.
      A diagnosis of cerebral venous thrombosis with subarachnoid hemorrhage was made.
      We started intravenous administration of unfractionated heparin. After 6 days in
      hospital, the right hemiparesis and motor aphasia worsened, and brain computed
      tomographic(CT)images demonstrated intracerebral hemorrhage in the left parietal
      lobe. Therefore, we switched treatment from heparin to apixaban. His condition
      improved and a brain magnetic resonance(MR)venogram after 7 days in hospital
      showed recanalization of the cerebral veins. He was discharged with no apparent
      neurological defects 33 days after onset and his modified Rankin Scale score was
      1. In cases of progressive cerebral venous thrombosis with intracerebral
      hemorrhage, during anticoagulation, it is necessary to achieve recanalization of
      the occluded cerebral vein rapidly without spreading the intracerebral
      hemorrhage. Factor Xa inhibitors, especially apixaban, may be another option for
      treating cerebral venous thrombosis with intracerebral hemorrhage.

PMID- 29172204
TI  - [Primary Intracranial Malignant Lymphoma Associated with Acquired
      Immunodeficiency Syndrome(AIDS):A Case Report].
AB  - The spread of human immunodeficiency virus(HIV)infection may result in an
      increased likelihood of surgery in patients with HIV infection. We treated a
      patient with intracranial malignant lymphoma associated with acquired
      immunodeficiency syndrome(AIDS)caused by HIV infection. The recommendations of
      the countermeasure manual for AIDS were followed. Only surgical staff without
      finger injury or inflammation were permitted to be involved in the operation. All
      staff were dressed in a waterproof, full-body surgical gown, and wore double
      gloves, double foot covers, and an N95 mask. The surgery could be performed
      safely with such infection control measures. Histological examination revealed a
      diffuse large B-cell lymphoma. The patient was referred to the Division of
      Infectious Diseases and Respiratory Medicine for chemotherapy.

PMID- 29172205
TI  - [A Case of Multiple Atherosclerotic Fusiform Cerebral Aneurysms with Repeated
      Subarachnoid Hemorrhage].
AB  - Pure fusiform aneurysms without dissection are considered to have a low risk of
      rupture. Furthermore, aneurysm wall with atherosclerotic change tends to be less
      susceptible to rupture. We present a rare case of multiple atherosclerotic
      fusiform aneurysms associated with repeated subarachnoid hemorrhage(SAH)during a
      9-year observation period. A 34-year-old woman was admitted to our hospital
      because of SAH. SAH with a temporal hematoma due to a fusiform aneurysm of the
      right middle cerebral artery(MCA)was detected using computed tomography(CT).
      Associated fusiform aneurysms were observed in the left posterior cerebral
      artery(PCA)and the left MCA. The right MCA aneurysm was occluded with
      angioplastic clipping. Eight years after the first onset, angioplastic clipping
      was performed on the other two fusiform aneurysms because of their growth.
      Intraoperative findings showed atherosclerotic change in the parent artery wall,
      similar to the right MCA aneurysms. The right MCA aneurysm ruptured again 1 year
      later. The aneurysm was treated with proximal occlusion combined with a bypass
      from the occipital artery to the distal MCA. The patient was in a stable state,
      although, she was disabled because of SAH damage. The effects of atherosclerotic
      fusiform aneurysms, which are rarely encountered, are not well known. Some
      studies have reported the risk of hemorrhage from these aneurysms. This case
      suggests the necessity of long-term follow-up for the prediction of aneurysm
      growth and bleeding. Moreover, proximal occlusion combined with an external
      bypass is better for the treatment of this type of aneurysm because angioplastic
      clipping is not curative.

PMID- 29172206
TI  - [A Case of Stent-Assisted Coil Embolization for Ruptured Anterior Inferior
      Cerebellar Aneurysm after Iatrogenic Vertebral Arteriovenous Fistula].

PMID- 29172207
TI  - [Usefulness of Thin-Slab Maximum Intensity Projections in Imaging of the Multiple
      Aneurysms that Arise at the Distal Portion of the Posterior Inferior Cerebellar
      Artery].

PMID- 29172208
TI  - [A Case of Creutzfeldt-Jakob Disease before Trepanation Presenting as a Chronic
      Subdural Hematoma].

PMID- 29172209
TI  - [Clinical Applications of Positron Emission Tomography for
      Neurosurgery(4)Applications of Positron Emission Tomography for Assessing Brain
      Tumors].

PMID- 29172210
TI  - Latest Generation of Balloon-Expandable Valve, the Edwards Sapien 3 Valve: Less
      Paravalvular Regurgitation but Higher Transvalvular Pressure Gradients.

PMID- 29172211
TI  - Local and Lower Limb Complications during and after Femoral Cannulation for
      Extracorporeal Life Support.

PMID- 29172212
TI  - Effect of Sustained Use of Aspirin until the Time of Surgery on Outcomes
      following Coronary Artery Bypass Grafting: A Randomized Clinical Trial.
AB  - BACKGROUND: The topic of aspirin (acetylsalicylic acid, ASA) use in coronary
      artery disease patients planned for coronary artery bypass grafting during
      perioperative period is among the most disputed issues in cardiac surgery. We
      designed a study to weigh the risks and benefits of continued ASA ingestion until
      the time of surgery. METHODS: In this randomized double-blind clinical trial, 206
      consecutive patients scheduled for isolated coronary artery bypass surgery (CABG)
      were randomly stratified into two groups. In group 1 (104 cases), patients were
      given 80 mg ASA per day until the day of surgery. In group 2 (102 patients), ASA
      (80 mg per day) was stopped 4 days before the operation. Patients in these two
      groups were similar in terms of preoperative patient and procedural
      characteristics. ASA was resumed 24 hours after the surgery in all patients.
      RESULTS: The rates of bleeding and reexploration within 24 hours of surgery were
      significantly higher in group 1 (824.3 vs. 492.1 mL, p < 0.001 and 5.7% vs. 0, p
      = 0.0138, respectively). The amount of intra- and postoperative packed red blood
      cell (PRBC) transfusion was considerably greater in group 1 (mean: 1.83 vs. 0.71
      units, p < 0.001). The rate of hospital mortality was similar (1.9% in both the
      groups, p = 0.98). Patients in group 1 had significantly longer mean hospital
      stay than patients in group 2 (8 vs. 5.1 days, p < 0.001). Again the time
      interval between weaning from heart-lung machine and closing the sternum was
      strikingly longer in group 1 (mean: 32.1 vs. 14.5 minutes, p < 0.001). The
      incidence of adverse postoperative outcomes such as myocardial infarction,
      stroke, and renal failure was not statistically different between the two groups.
      CONCLUSION: Sustained ASA use until the day of surgery in patients planned for
      elective isolated CABG can result in excessive bleeding, increased rate of
      reexploration, and need for more PRBC transfusion without any proven beneficial
      effect on reducing unfavorable postoperative outcomes. Hence, we recommend
      discontinuing ASA between 3 and 5 days before non-urgent CABG while keeping it on
      in nonelective circumstances.

PMID- 29172213
TI  - In Situ Endothelialization Promoted by SEMA4D and CXCL12 for Titanium-Based
      Biomaterials.
AB  - In situ endothelialization, aiming to create implantation surfaces capable of
      self-endothelialization, seems to be an extremely promising solution,
      particularly on those blood-contacting surfaces. In this research study, we
      immobilized the soluble semaphorin 4D (SEMA4D) and C-X-C motif chemokine ligand
      12 (CXCL12) biomolecules together with heparin onto the metal-based biomaterial
      surfaces to achieve in situ endothelialization of modified samples both by
      stimulating the neighboring endothelial cells (ECs) migration and by capturing
      the circulating endothelial progenitor cells (EPCs) directly from the blood
      circulation. X-ray photoelectron spectroscopy data demonstrate the successful
      immobilization of SEMA4D and CXCL12. Due to the presence of heparin,
      hemocompatibility was also improved after modification. Although EC migration was
      mainly mediated by SEMA4D with the coordination of CXCL12, EC proliferation and
      haptotaxis property were also enhanced, while EC chemotaxis was slightly
      suppressed because the further immobilization of CXCL12 influences the release of
      SEMA4D. The results of the ex vivo EPC capturing assay indicated the mobilization
      of CXCL12 promotes EPC adhesion. In vivo implantation further demonstrated that
      CXCL12 cooperates with SEMA4D to promote a process of in situ endothelialization.

PMID- 29172214
TI  - Complications of Implanted Nonbiologic Devices-An Overview.
AB  - Under physiologic conditions, blood is contained within the vascular space lined
      with smooth endothelial cells. When various devices made of nonbiologic material
      are implanted, blood will be exposed to a foreign surface. A series of events
      ensue and may lead to many complications, including thrombosis, hemolysis,
      thrombocytopenia, bleeding, infection, and malfunction of the device. The
      incidence, manifestations, and special characteristics of these complications
      vary with different types of implanted devices. However, they have in common an
      important pathogenic pathway that of an exposure to a foreign surface. Despite
      the development of improved versions of these devices, more research on the
      causative factors of these complications is needed to take preventive and
      corrective measures, particularly those that enhance the process of healing by re
      endothelialization of the foreign surface. This article is a brief review of the
      complications encountered in blood-contacting devices.

PMID- 29172215
TI  - Factor VII-Activating Protease: Hemostatic Protein or Immune Regulator?
AB  - Factor VII (FVII)-activating protease (FSAP) is a serine protease in plasma,
      which was initially described to play a role in coagulation by activation of
      FVII, independent of tissue factor, and in fibrinolysis by cleavage of single
      chain urokinase. Recent studies, however, suggest that FSAP-mediated FVII
      cleavage is negligible and that FSAP may exert procoagulant functions via
      cleavage of tissue factor pathway inhibitor. Meanwhile, many substrates of FSAP
      have been identified, such as platelet-derived growth factor, basic fibroblast
      growth factor/epidermal growth factor, histones, and high-molecular-weight
      kininogen. FSAP has also shown to induce DNA released from dead cells. Given its
      propensity for autoproteolysis and degradation, studies on the activation and
      regulation of FSAP are difficult to perform. Recent animal studies suggest a role
      of FSAP in the pathogenesis of arteriosclerosis, vascular integrity and probably
      also in the regulation of coagulation initiation. This review will focus on the
      biochemical properties of FSAP, regulation of FSAP activation, and finally its
      role in vascular disease and acute systemic inflammatory diseases, such as
      sepsis.

PMID- 29172216
TI  - The economic impact of using single-operator cholangioscopy for the treatment of
      difficult bile duct stones and diagnosis of indeterminate bile duct strictures.
AB  - BACKGROUND AND STUDY AIM: Conventional endoscopic retrograde
      cholangiopancreatography (ERCP) combines endoscopy and radiography to diagnose
      and treat pathological conditions of the bile duct. The aim of the present
      analysis was to evaluate the clinical and economic impact of the use of single
      operator intraductal cholangioscopy (IDC), which allows for direct visualization
      of the bile duct, as an alternative to ERCP for the treatment of difficult bile
      duct stones and the diagnosis of bile duct strictures. PATIENTS AND METHODS: The
      clinical and economic consequences of single-operator IDC use were evaluated
      using two decision-tree models, one for management of difficult-to-remove stones
      and one for stricture diagnosis. A hospital perspective was adopted. Data to
      populate the models were derived from two Belgian hospitals that specialize in
      endoscopic procedures of the bile duct. Overall, the examined population
      consisted of 62 patients with difficult stones and 49 patients with indeterminate
      strictures. RESULTS: In the model for difficult stone management, the use of IDC
      determined a decrease in the number of procedures (- 27 % relative reduction) and
      costs (- ?73 000; - 11 % relative reduction) when compared with ERCP. In the
      model for stricture diagnosis, the use of IDC determined a decrease in the number
      of procedures (- 31 % relative reduction) and costs (- ?13 000; - 5 % relative
      variation) when compared with ERCP. CONCLUSIONS: The single-operator IDC system
      performed better than ERCP for the treatment of difficult bile duct stones and
      the diagnosis of bile duct strictures, and reduced the overall expenditure in
      hospitals in Belgium.

PMID- 29172217
TI  - ?

PMID- 29172218
TI  - [Demographic and Social Transitions - Results of the Working Group 2 of the Forum
      Future Public Health, Berlin 2016].
AB  - Demographic and social transformation occur due to changes in the structure of
      the population and employment especially of women, increasing cultural diversity,
      unequal educational opportunities for children and adolescents, and regional
      variation in the provision of services. Meeting the challenges requires flexible,
      responsive and integrated social and health care systems that allow participation
      of individuals and groups concerned and recognition of their views and
      perspectives. Health monitoring and knowledge management is adjusted to the needs
      of the population and transfers high quality, evidence-based knowledge into all
      policy areas (health in all policies strategy).

PMID- 29172219
TI  - [New Ways of Communication - Results of the Working Group 5 of the Forum Future
      Public Health, Berlin 2016].
AB  - Good communication is an essential feature of public health. The existing
      communication channels from sender to receiver are increasingly supplemented or
      even replaced by new forms of communication such as social media in all areas of
      life. Public Health must adopt these changes in order to make its concerns and
      results accessible to different user groups. 1. Many groups of the population (e.
      g. migrants, socially disadvantaged) are hard to reach for purposes of
      communication. Different addressees need different forms of communication,
      including social media. Appropriate access routes must be identified and used for
      communication. 2. Strategies must be developed on how public health information
      can be effectively communicated via social media. They must be professionally
      sound, reliable and quality-assured, and regular updating must ensured. 3.
      Participation and dialogue are important elements of effective public health
      communication.

PMID- 29172220
TI  - [Strengthening Public Health by Strengthening Public Health Research - Results of
      the Working Group 7 of the Forum Future Public Health, Berlin 2016].
AB  - Public health research is application-oriented, its great potential lies in the
      interlinking of science and practice, as well as its interdisciplinarity and
      methodological competence. Public health research is focused on the development
      and evaluation of measures to protect and improve the health of the population.
      In doing so, it must make its contribution to tackling the new challenges posed
      by demographic change, digitalization, new forms of communication and medical
      progress. By pooling the forces, the public health scientists should actively
      contribute to policy advice and promoting adequate research funding.

PMID- 29172221
TI  - [Education and Training in Public Health - Results of the Working Group 9 of the
      Forum Future Public Health, Berlin 2016].
AB  - The need for a qualified public health workforce can only be met by appropriate
      provision of a wide spectrum of basic, advanced and continuing education and
      training programs on public health that meet international standards. At the same
      time, efforts must be made to offer young academics attractive career
      opportunities. Training in public health competences must also be provided for
      allied professionals in health care and for professions with influence on the
      determinants of health such as urban planning or agricultural science. This
      report from a working group meeting at the 'Public Health Zukunftsforum 2016' in
      Berlin presents ideas for the further development of training in public health in
      Germany.

PMID- 29172222
TI  - [Surveillance and Monitoring - Results of the Working Group 10 of the Forum
      Future Public Health, Berlin 2016].
AB  - Evidence-based health policies and evidence-based measures need comprehensive
      information on the health of the population. The existing health surveillance
      system provides reliable answers to many health policy issues. Nonetheless, there
      are many information gaps not yet covered or are only covered via short-term
      project solutions. 1. We need to strengthen and expand existing health
      surveillance and monitoring to continuously collect information on the health
      status of all population groups, including those that are difficult to reach
      through the existing surveys and methods, such as people with a migration
      background, or socially disadvantaged. This information must be regularly
      available on the national, regional and also on the local level. 2. The use of
      existing data on health, for example from official statistics or social
      insurance, must be significantly expanded and strengthened. The infrastructure
      for scientific analyses of health data as well as the transfer of information to
      policy makers and the public must be strengthened. Through an expansion of the
      resources for scientific processing of health-relevant questions, Public Health
      can make an important contribution to effective health policies.

PMID- 29172223
TI  - [Governance - Government Action: Strengthening the Public's Health by more Public
      Accountability for Health - Results of the Working Group 11 of the Forum Future
      Public Health, Berlin 2016].
AB  - There is a considerable need for action to systematically strengthen public
      health in Germany by increasing public responsibility for health. A Good
      Governance approach for health has not yet been developed. The main areas of
      action would be the establishment of a health impact assessment for proposed
      legislation, the expansion of public health services and a new role for
      structural interventions for disease prevention and health promotion. It is also
      necessary to focus government action on the provision of public health services
      and - related to that - on strengthening the municipal level as a relevant
      decision-making structure for health.

PMID- 29172224
TI  - [Public Health Research in Germany: A Appraisal - Plenary Lecture of the Forum
      Future Public Health, Berlin 2016].
AB  - Public health research incorporates many domains and has an interdisciplinary
      structure, which allows it to take on a leadership role in improving population
      health. In particular, the methodological expertise and applied approaches in
      this field should be used more often to allow translational science concepts to
      go beyond the patient bedside back to the population setting. New methods of data
      collection and the development of concepts to achieve more precise interventions
      require innovative contributions from experts in public health research. With the
      use of innovative methods of public health research, improvements in population
      health can be achieved, including all sections of the population.

PMID- 29172225
TI  - [Fragmented Heterogeneity as Leitmotiv of Public Health Practice in Germany? -
      Plenary Lecture at the Forum Future Public Health, Berlin 2016].
AB  - Heterogeneity is a constitutive element of public health practice in Germany. The
      Public Health Service as a traditional field of public health is - like the
      currently booming health promotion and disease prevention landscape - faced with
      major challenges in its attempt to create more health for vulnerable population
      groups. Additional expenditure on small-scale prevention concepts and
      interventions and vastly differentiated job profiles are not per se beneficial to
      achieve this aim. The future of public health practice lies rather in the
      development of integrated communal concepts of action such as prevention chains.

PMID- 29172226
TI  - [Research Networks in Public Health: Requirements for Sustainability and
      Effectiveness - a Sociological Perspective].
AB  - The Public Health White Paper draws up a vision of public health as a living,
      decentralized network that can help improve the health of the population in a
      sustained fashion. However, the central question remains open as to which
      prerequisites public health networks should fulfill in order to be effective in
      the long term. The aim of this paper is to provide a sociological view of the
      issue and offer some discussion ideas. Parsons' structural functionalism leads to
      the thesis that science networks in public health require structures that ensure
      that the 4 basic functions of viable social networks - (1) adaptation, (2) goal
      attainment, (3) integration and (4) latent pattern maintenance - are fulfilled.
      On this theoretical basis, suggestions are made to establish functional formal
      structures in public health networks.

PMID- 29172228
TI  - Adverse life events increase risk for postpartum psychiatric episodes: A
      population-based epidemiologic study.
AB  - BACKGROUND: Trauma histories may increase risk of perinatal psychiatric episodes.
      We designed an epidemiological population-based cohort study to explore if
      adverse childhood experiences (ACE) in girls increases risk of later postpartum
      psychiatric episodes. METHODS: Using Danish registers, we identified women born
      in Denmark between January 1980 and December 1998 (129,439 childbirths). Exposure
      variables were ACE between ages 0 and 15 including: (1) family disruption, (2)
      parental somatic illness, (3) parental labor market exclusion, (4) parental
      criminality, (5) parental death, (6) placement in out-of-home care, (7) parental
      psychopathology excluding substance use, and (8) parental substance use disorder.
      Primary outcome was first occurrence of in- or outpatient contact 0-6 months
      postpartum at a psychiatric treatment facility with any psychiatric diagnoses,
      ICD-10, F00-F99 (N = 651). We conducted survival analyses using Cox proportional
      hazard regressions of postpartum psychiatric episodes. RESULTS: Approximately 52%
      of the sample experienced ACE, significantly increasing risk of any postpartum
      psychiatric diagnosis. Highest risks were observed among women who experienced
      out-of-home placement, hazard ratio (HR) 2.57 (95% CI: 1.90-3.48). Women
      experiencing two adverse life events had higher risks of postpartum psychiatric
      diagnosis HR: 1.88 (95% CI: 1.51-2.36), compared to those with one ACE, HR: 1.24
      (95% CI: 1.03-49) and no ACE, HR: 1.00 (reference group). CONCLUSIONS: ACE
      primarily due to parental psychopathology and disability contributes to increased
      risk of postpartum psychiatric episodes; and greater numbers of ACE increases
      risk for postpartum psychiatric illness with an observed dose-response effect.
      Future work should explore genetic and environmental factors that increase risk
      and/or confer resilience.

PMID- 29172229
TI  - Context matters: a multicountry analysis of individual- and neighbourhood-level
      factors associated with women's sanitation use in sub-Saharan Africa.
AB  - OBJECTIVES: To identify cross-national trends in factors associated with women's
      sanitation use in sub-Saharan Africa. METHODS: Using data from Demographic and
      Health Surveys conducted in 14 SSA countries between 2008 and 2014, we modelled
      women's sanitation use in relation to various individual- and neighbourhood-level
      factors. RESULTS: Substantial variation exists between countries in the strength
      and direction of factors associated with sanitation use. Particularly significant
      associations across the region included access to different water sources, years
      of education, family size, age, living in a female-headed household, being
      married and wealth. Neighbourhood-level poverty, ethnic diversity and
      urbanisation were important factors in a majority of countries. CONCLUSIONS:
      International development goals for sanitation are frequently framed in terms of
      availability, implicitly suggesting that if facilities are accessible, they will
      be used. A more nuanced view that takes into account not only the existence of
      facilities but also the factors influencing their use is needed to understand the
      dynamics of women's sanitation use in the region. Policies focused on
      availability may not yield the desired public health benefits from improved
      sanitation in sub-Saharan Africa. Context-relevant factors must be addressed
      concurrently to achieve sanitation development goals.

PMID- 29172227
TI  - Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress
      symptoms in U.S. military veterans: Results from the National Health and
      Resilience in Veterans Study.
AB  - BACKGROUND: Previous research examining the association between apolipoprotein E
      (APOE) gene polymorphism and risk for posttraumatic stress disorder (PTSD) has
      been inconsistent due to the use of small and select samples. This study examined
      the relation between APOE genotype and PTSD symptoms in two nationally
      representative samples of U.S. military veterans. The potential effect of
      cumulative trauma burden and social support in moderating this association was
      also evaluated. METHODS: The main sample consisted of 1,386 trauma-exposed
      European American (EA) veterans (mean age: 62-63 years) who participated in the
      National Health and Resilience in Veterans Study (NHRVS) in 2011. The independent
      replication sample consisted of 509 trauma-exposed EA veterans from the 2013
      NHRVS. RESULTS: APOE epsilon4 allele carriers reported significantly greater
      severity of PTSD symptoms than noncarriers in the main, but not the replication,
      sample. In both samples, the interaction of APOE epsilon4 carrier status and
      cumulative trauma burden was associated with greater severity of PTSD symptoms (F
      range = 2.53-8.09, all P's < .01), particularly re-experiencing/intrusion
      symptoms (F range = 3.59-4.24, P's < .001). Greater social support was associated
      with lower severity of PTSD symptoms among APOE epsilon4 allele carriers with
      greater cumulative trauma burden (beta range -.27 to -.60, P's < .05).
      CONCLUSION: U.S. military veterans who are APOE epsilon4 allele carriers and
      exposed to a high number of traumas may be at increased risk for developing PTSD
      symptoms than epsilon4 noncarriers. Greater social support may moderate this
      association, thereby highlighting the potential importance of social support
      promoting interventions in mitigating the effect of epsilon4 * cumulative trauma
      burden on PTSD risk.

PMID- 29172230
TI  - Sequential gene activation and gene imprinting during early embryo development in
      maize.
AB  - Gene imprinting is a widely observed epigenetic phenomenon in maize endosperm;
      however, whether it also occurs in the maize embryo remains controversial. Here,
      we used high-throughput RNA sequencing on laser capture microdissected and
      manually dissected maize embryos from reciprocal crosses between inbred lines B73
      and Mo17 at six time points (3-13 days after pollination, DAP) to analyze allelic
      gene expression patterns. Co-expression analysis revealed sequential gene
      activation during maize embryo development. Gene imprinting was observed in maize
      embryos, and a greater number of imprinted genes were identified at early embryo
      stages. Sixty-four strongly imprinted genes were identified (at the threshold of
      9:1) on manually dissected embryos 5-13 DAP (more imprinted genes at 5 DAP).
      Forty-one strongly imprinted genes were identified from laser capture
      microdissected embryos at 3 and 5 DAP (more imprinted genes at 3 DAP).
      Furthermore, of the 56 genes that were completely imprinted (at the threshold of
      99:1), 36 were not previously identified as imprinted genes in endosperm or
      embryos. In situ hybridization demonstrated that most of the imprinted genes were
      expressed abundantly in maize embryonic tissue. Our results shed lights on early
      maize embryo development and provide evidence to support that gene imprinting
      occurs in maize embryos.

PMID- 29172231
TI  - Children with optic nerve hypoplasia face a high risk of neurodevelopmental
      disorders.
AB  - AIM: Optic nerve hypoplasia (ONH) is a congenital ocular malformation that has
      been associated with neurodevelopmental disorders, but the prevalence in
      unilateral disease and less severe visual impairment is unknown. We studied
      intellectual disability and autism spectrum disorders (ASDs) in patients with
      ONH. METHODS: This was a population-based cross-sectional cohort study of 65
      patients (33 female) with ONH below 20 years of age, living in Stockholm in
      December 2009, with data analysed in January 2016. Of these 35 were bilateral and
      30 were unilateral. Neurodevelopmental disorders were diagnosed or confirmed by
      neurological assessments, the Five to Fifteen parent questionnaire and reviewing
      previous neuropsychological investigations or conducting neuropsychological
      tests. RESULTS: Bilateral ONH patients had lower mean full scale intelligence
      quotient scores than unilateral patients (84.4 and 99.4, respectively, p =
      0.049). We assessed intellectual disability in 55 eligible patients, and it was
      more common in patients with bilateral ONH (18 of 32, 56%) than unilateral ONH
      (two of 23, 9%, p < 0.001). ASDs were diagnosed in seven of 42 (17%) patients.
      CONCLUSION: Children with bilateral ONH had a high risk of neurodevelopmental
      disorders, especially intellectual disability. The risk was lower in unilateral
      ONH, but the levels of neurodevelopmental disorders warrant screening of both
      groups.

PMID- 29172232
TI  - Review demonstrates that less invasive surfactant administration in preterm
      neonates leads to fewer complications.
AB  - : Surfactant treatment of neonatal respiratory distress syndrome (RDS) was
      introduced in Europe during the 1990s. Meta-analyses have indicated that using
      less invasive surfactant administration techniques on preterm neonates receiving
      continuous positive airway pressure (CPAP) results in improved survival rates
      without bronchopulmonary dysplasia. Surfactant should be administered early and
      ventilator settings adapted to changing oxygen requirements and lung mechanics.
      Side effects including initial bradycardia, oxygen desaturation, tube obstruction
      and isolated cases of pulmonary haemorrhage have been reported. CONCLUSION: Less
      invasive surfactant therapy improves pulmonary outcomes in preterm neonates with
      RDS and should ideally be administered in combination with CPAP.

PMID- 29172233
TI  - Stronger selective constraint on downstream genes in the oxidative
      phosphorylation pathway of cetaceans.
AB  - The oxidative phosphorylation (OXPHOS) pathway is an efficient way to produce
      energy via adenosine triphosphate (ATP), which is critical for sustaining an
      energy supply for cetaceans in a hypoxic environment. Several studies have shown
      that natural selection may shape the evolution of the genes involved in OXPHOS.
      However, how network architecture drives OXPHOS protein sequence evolution
      remains poorly explored. Here, we investigated the evolutionary patterns of genes
      in the OXPHOS pathway across six cetacean genomes within the framework of a
      functional network. Our results show a negative correlation between the strength
      of purifying selection and pathway position. This result indicates that
      downstream genes were subjected to stronger evolutionary constraints than
      upstream genes, which may be due to the dual function of ATP synthase in the
      OXPHOS pathway. Additionally, there was a positive correlation between codon
      usage bias and omega (omega = dN/dS) and a negative correlation with synonymous
      substitution rate (dS), indicating that the stronger selective constraint on
      genes (with less biased codon usage) along the OXPHOS pathway is attributable to
      an increase in the rate of synonymous substitution. Surprisingly, there was no
      significant correlation between protein-protein interactions and the evolutionary
      estimates, implying that highly connected enzymes may not always show greater
      evolutionary constraints. Compared with that observed for terrestrial mammals, we
      found that the signature of positive selection detected in five genes (ATP5J,
      LHPP, PPA1, UQCRC1 and UQCRQ) was cetacean-specific, reflecting the importance of
      OXPHOS for survival in hypoxic, aquatic environments.

PMID- 29172234
TI  - Barriers to participation in a sexual health intervention for men following
      treatment for rectal and anal cancer.

PMID- 29172235
TI  - The association between atopic dermatitis and hand eczema: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Atopic dermatitis (AD) and hand eczema (HE) are common chronic and
      relapsing inflammatory skin conditions that often co-occur. OBJECTIVES: While
      several studies have addressed their relationship, the exact association estimate
      is unknown. METHODS: We systematically reviewed published literature on the
      association between AD and HE in PubMed, Embase and Web of Science using the
      following search terms: (atopic dermatitis OR atopic eczema) AND (hand dermatitis
      OR hand eczema). Meta-analyses were then performed to examine the association
      between AD and the point, 1-year and lifetime prevalence of HE, respectively.
      RESULTS: We identified 35 relevant studies, of which 26 were included in the meta
      analyses. AD was associated with an increased prevalence of HE with regard to
      point [odds ratio (OR) 2.35; 95% confidence interval (CI) 1.47-3.76], 1-year (OR
      4.29; 95% CI 3.13-5.88) and lifetime prevalence (OR 4.06; 95% CI 2.72-6.06).
      Furthermore, positive associations between AD and occupational HE were identified
      when assessing the 1-year (OR 4.31; 95% CI 2.08-8.91) and lifetime prevalence (OR
      2.81; 95% CI 2.08-3.79). Similar positive associations were found in the general
      population studies, i.e. OR 4.19 (95% CI 3.46-5.08) and OR 5.69 (95% CI 4.41
      7.36). CONCLUSIONS: Important study limitations include the wide use of
      questionnaire studies, and lack of prospective studies as well as poor clinical
      phenotype descriptions. In conclusion, our systematic review and meta-analysis
      showed that patients with AD had a strongly increased prevalence of HE.
      Clinicians should continue to guide patients with AD away from occupations with a
      high risk of HE.

PMID- 29172236
TI  - What is the optimal management of an intra-operative air leak in a colorectal
      anastomosis?
AB  - AIM: An airtight anastomosis on intra-operative leak testing has been previously
      demonstrated to be associated with a lower risk of clinically significant
      postoperative anastomotic leak following left-sided colorectal anastomosis.
      However, to date, there is no consistently agreed upon method for management of
      an intra-operative anastomotic leak. Therefore, we powered a noninferiority study
      to determine whether suture repair alone was an appropriate strategy for the
      management of an intra-operative air leak. METHOD: This is a retrospective cohort
      analysis of prospectively collected data from a tertiary care referral centre. We
      included all consecutive patients with left-sided colorectal or ileorectal
      anastomoses and evidence of air leak during intra-operative leak testing.
      Patients were excluded if proximal diversion was planned preoperatively, a pre
      existing proximal diversion was present at the time of surgery or an anastomosis
      was ultimately unable to be completed. The primary outcome measure was clinically
      significant anastomotic leak, as defined by the Surgical Infection Study Group at
      30 days. RESULTS: From a sample of 2360 patients, 119 had an intra-operative air
      leak during leak testing. Sixty-eight patients underwent suture repair alone and
      51 underwent proximal diversion or anastomotic reconstruction. The clinically
      significant leak rate was 9% (6/68; 95% CI: 2-15%) in the suture repair alone arm
      and 0% (0/51) in the diversion or reconstruction arm. CONCLUSION: Suture repair
      alone does not meet the criteria for noninferiority for the management of intra
      operative air leak during left-sided colorectal anastomosis. Further repair of
      intra-operative air leak by suture repair alone should be reconsidered given
      these findings.

PMID- 29172237
TI  - Estimation and validation of patient-specific high-resolution lung elasticity
      derived from 4DCT.
AB  - PURPOSE: Lung diseases are commonly associated with changes in lung tissue's
      biomechanical properties. Functional imaging techniques, such as elastography,
      have shown great promise in measuring tissue's biomechanical properties, which
      could expand the utility and effectiveness of radiotherapy treatment planning. We
      present a novel methodology for characterizing a key biomechanical property,
      parenchymal elasticity, derived solely from 4DCT datasets. METHODS: Specifically,
      end-inhalation and end-exhalation breathing phases of the 4DCT datasets were
      deformably registered and the resulting displacement maps were considered to be
      ground-truth. A mid-exhalation image was also prepared for verification purposes.
      A GPU-based biomechanical model was then generated from the patient end
      exhalation dataset and used as a forward model to iteratively solve for the
      elasticity distribution. Displacements at the surface of the lungs were applied
      as boundary constraints for the model-guided tissue elastography, while the inner
      voxels were allowed to deform according to the linear elastic forces within the
      biomechanical model. A convergence criteria of 10% maximum deformation was
      employed for the iterative process. RESULTS: The lung tissue elasticity
      estimation was documented for a set of 15 4DCT patient datasets. Maximum lung
      deformations were observed to be between 6 and 31 mm. Our results showed that, on
      average, 89.91 +/- 4.85% convergence was observed. A validation study consisting
      of mid-exhalation breathing phases illustrated an accuracy of 87.13 +/- 10.62%.
      Structural similarity, normalized cross-correlation, and mutual information were
      used to quantify the degree of similarity between the following image pairs: (a)
      the model-generated end-exhalation and ground-truth end-exhalation, and (b) model
      generated mid-exhalation images and ground-truth mid-exhalation. CONCLUSIONS:
      Overall, the results suggest that the lung elasticity can be measured with
      approximately 90% convergence using routinely acquired clinical 4DCT scans,
      indicating the potential for a lung elastography implementation within the
      radiotherapy clinical workflow. The regional lung elasticity found here can lead
      to improved tissue sparing radiotherapy treatment plans, and more precise
      monitoring of treatment response.

PMID- 29172238
TI  - Women who had positive relationships with their own mothers reported good
      attachments to their first child before and after birth.
AB  - AIM: Bowlby's attachment intergenerational transmission theory suggests that a
      woman's attachment to her parents, particularly her mother, plays an important
      role in her future parenting. We studied whether there was any association
      between pregnant women's attachment to their baby before and after birth and
      their relationships with their mothers. METHODS: A longitudinal study was carried
      out in 2015 on 201 first-time mothers recruited in the maternity ward of the
      level two Misericordia e Dolce Hospital in Prato, Italy. At 32 weeks of
      pregnancy, the women filled in the Parental Bonding Instrument and the Prenatal
      Attachment Inventory and their spontaneous attachment behaviour towards their
      newborn infants were observed in the nursery during the first two days after
      childbirth. RESULTS: Having a good relationship with their own mothers was a
      positive predictor for the women's prenatal attachment to their baby and
      caregiving and attachment behaviour to their newborn infants. In addition, the
      mothers' prenatal attachment positively predicted their behavioural attachment
      pattern after birth. CONCLUSION: We found that women who had positive
      relationships with their own mothers also had positive attachments to their
      unborn babies and in the period immediately after birth. Our findings supported
      Bowlby's attachment intergenerational transmission theory.

PMID- 29172239
TI  - Strictly controlled glucose infusion rates are associated with a reduced risk of
      hyperglycaemia in extremely low birth weight preterm infants.
AB  - AIM: We evaluated a strict strategy that aimed to avoid fluctuations in glucose
      infusion rates (GIRs) and assessed the independent effects of maximal daily GIRs
      on the hyperglycaemia risk among extremely low birth weight (ELBW) infants
      receiving early enhanced parenteral nutrition. METHODS: This study comprised all
      ELBW infants admitted to the neonatal intensive care unit of Oslo University
      Hospital Rikshospitalet, Norway, before (2007-2009) and after (2012-2013)
      implementing a strict GIR strategy. Severe hyperglycaemia was defined as two
      consecutive blood glucose values over 12 mmol/L. Maximum daily GIRs (mg/kg/min)
      were categorised into low (<5.1), intermediate (5.1-7.0) or high (>7.0). Mixed
      effects logistic regression modelling for repeated measurements was applied to
      investigate independent determinants of hyperglycaemia. RESULTS: We included 1293
      treatment days for 195 infants. The maximum daily GIR decreased (6.3 versus 5.8
      mg/kg/min), while mean daily glucose and energy intakes were maintained in the
      post-strategy period. The prevalence of severe hyperglycaemia (48% versus 23%),
      insulin use (39% versus 16%) and mortality (26% versus 10%) fell. Intermediate
      GIR (odds ratio 2.11) and high GIR (odds ratio 2.85) were significant independent
      predictors of severe hyperglycaemia compared to low GIR. CONCLUSION: A strict GIR
      strategy reduced the risk of severe hyperglycaemia and adverse outcomes.

PMID- 29172240
TI  - Disseminated mucormycosis masquerading as rejection early after orthotopic heart
      transplantation.
AB  - Mucorales organisms are an uncommon cause of invasive fungal infections after
      solid organ transplantation but are associated with great morbidity and
      mortality. We report a fatal case of disseminated Cunninghamella infection early
      after heart transplantation. The patient developed graft dysfunction and elevated
      markers of myocyte injury and autopsy revealed fulminant fungal myocarditis. This
      case highlights the need for a high index of suspicion in immunocompromised
      patients who are not improving with standard antimicrobial therapy.

PMID- 29172241
TI  - The impact of resilience and subsequent stressful life events on MDD and GAD.
AB  - BACKGROUND: There remains a dearth of research examining the "buffering" effect
      of resilience, wherein resilience at one point in time would be expected to
      protect an individual against development of psychopathology following future
      adverse life events. METHODS: Using longitudinal data from an epidemiological
      twin sample (N = 7463), this study tested whether resilience would act as a
      buffer for stressful life events (SLEs) against risk for major depressive
      disorder (MDD) and generalized anxiety disorder (GAD). Resilience, demographics,
      and psychopathology were measured at Time 1 and recent SLEs and current MDD and
      GAD were measured at Time 2. RESULTS: Final models, controlling for demographic
      covariates and Time 1 diagnosis, examined the impact of Time 1 resilience, recent
      SLEs, their interaction, and a three-way interaction adding sex on MDD and GAD.
      CONCLUSIONS: The pattern of findings was the same for MDD and GAD, wherein main
      effects and two-way interactions of resilience and SLEs were significant, such
      that greater resilience was protective even in the context of high numbers of
      past-year SLEs. The three-way interaction was not significant, suggesting that
      the relationship between SLEs and resilience on psychopathology was the same for
      both men and women. Findings support the conceptualization of resilience as a
      buffer against the impact of future life stressors on common internalizing
      psychopathology. Longitudinal designs and trajectory-based studies that include
      recurring measures of SLEs could inform conceptualizations of resilience in the
      context of ongoing adversity and aid in developing interventions aimed at
      fostering healthy adaptation in the face of stressors.

PMID- 29172242
TI  - Upregulation of angiogenesis in oral lichen planus.
AB  - OBJECTIVES: As angiogenesis is fundamental to the pathogenesis of many chronic
      inflammatory disorders, this study investigated the expression of various
      vascular markers in oral lichen planus and non-specific oral mucosal inflammatory
      tissues. METHODS: Archival specimens of oral lichen planus (n = 15) and inflamed
      tissues (n = 13) were stained using immunohistochemistry with antibodies to CD34,
      vascular endothelial growth factor, vascular endothelial growth factor receptor
      and vasohibin. Nine representative sites at the epithelial-connective tissue
      junction and through the fibrous connective tissue were selected, and automated
      analysis techniques were used to determine the extent of positivity expressed as
      the percentage of positive cells. Significance was denoted when P < .05. RESULTS:
      The expression of pro-angiogenic factors was higher in lichen planus samples
      compared with inflamed controls. A higher level of CD34 was observed in the
      deeper parts of the connective tissue of Oral lichen planus (OLP) (P = .04),
      whereas VEGF and VEGFR2 expressions were higher all through the tissues
      (respectively, P < .02 and P < .01). The expression of the anti-angiogenic VASH1
      was higher in inflamed tissue compared with lichen planus in all sites evaluated
      (P < .01). CONCLUSIONS: The findings indicate that angiogenic factors are
      differentially expressed in oral lichen planus compared with inflamed controls,
      with increased expression of pro-angiogenic factors and decreased anti-angiogenic
      expression.

PMID- 29172243
TI  - Characterization of 90 Y-SPECT/CT self-calibration approaches on the
      quantification of voxel-level absorbed doses following 90 Y-microsphere selective
      internal radiation therapy.
AB  - PURPOSE: 90 Y-microsphere selective internal radiation therapy (90 Y-SIRT or 90 Y
      radioembolization) is used in the management of unresectable liver tumors. 90 Y
      SIRT presents a unique situation where the total 90 Y activity inside the liver
      can be determined with high accuracy (> 95%). 90 Y bremsstrahlung single-photon
      emission computed tomography (SPECT)/computed tomography (CT) can be self
      calibrated to provide quantitative images that facilitate voxel-level absorbed
      dose calculations. We investigated the effects of different approaches for 90 Y
      SPECT self-calibration on the quantification of absorbed doses following 90 Y
      SIRT. METHODS: 90 Y bremsstrahlung SPECT/CT images of 31 patients with
      hepatocellular carcinoma, collected following 90 Y-SIRT, were analyzed, yielding
      48 tumor and 31 normal liver contours. We validated the accuracy of absorbed
      doses calculated by a commercial software against those calculated using Monte
      Carlo-based radiation transport. The software package was used to analyze the
      following definitions of SPECT volume of interest used for 90 Y-SPECT self
      calibration: (a) SPECT field-of-view (FOV), (b) chest-abdomen contour, (c) total
      liver contour, (d) total liver contour expanded by 5 mm, and (e) total liver
      contour contracted by 5 mm. Linear correlation and Bland-Altman analysis were
      performed for tumor and normal liver tissue absorbed dose volume histogram
      metrics between the five different approaches for 90 Y-SPECT self-calibration.
      RESULTS: The mean dose calculated using the commercial software was within 3% of
      Monte Carlo for tumors and normal liver tissues. The tumor mean dose calculated
      using the chest-abdomen calibration was within 2% of that calculated using the
      SPECT FOV, whereas the doses calculated using the total liver contour, expanded
      total liver contour, and contracted total liver contour were within 68%, 47%, and
      107%, respectively, of doses calculated using the SPECT FOV. The normal liver
      tissue mean dose calculated using the chest-abdomen contour was within 1.3% of
      that calculated using the SPECT FOV, whereas the doses calculated using the total
      liver contour, expanded total liver contour, and contracted total liver contour
      were within 73%, 50%, and 114%, respectively, of doses calculated using the SPECT
      FOV. CONCLUSIONS: The mean error of < 3% for commercial software can be
      considered clinically acceptable for 90 Y-SIRT dosimetry. Absorbed dose
      quantification using 90 Y-SPECT self-calibration with the chest-abdomen contour
      was equivalent to that calculated using the SPECT FOV, but self-calibration with
      the total liver contour yielded substantially higher (~70%) dose values. The
      large biases revealed by our study suggest that consistent absorbed dose
      calculation approaches are essential when comparing 90 Y-SIRT dosimetry between
      different clinical studies.

PMID- 29172244
TI  - Comparative study of amlodipine vs. cilnidipine for the prevention of hepatic
      ischemia-reperfusion injury in rat model.
AB  - Ca2+ signaling plays crucial role in ischemia and reperfusion (I/R) injury.
      Although blockade of L-type Ca2+ channels by amlodipine (AML) has been shown to
      suppress hepatic I/R injury in several animal models, information is still needed
      regarding the hepatoprotective effects of the dual L/N-type Ca2+ channel
      blockers, cilnidipine (CIL). We examined the effect of pretreatment with AML or
      CIL (100 MUg/kg i.p.) 45 min before induction of 60 min of liver ischemia
      followed by reperfusion, on oxidative stress markers, liver enzymes, serum tumor
      necrosis factor-alpha, interleukin-1beta, apoptosis markers, and nuclear factor
      KB after 6 and 24 h of hepatic reperfusion. Both drugs significantly ameliorated
      biochemical and histological markers of hepatic I/R injury, but protection with
      CIL was more significant at the 6-h time point where protection with AML
      outlasted that of CIL. Both drugs offered significant protection against hepatic
      I/R damage, but the protection with CIL seemed more potent but of shorter
      duration than that observed with AML possibly due to the shorter half-life of
      CIL.

PMID- 29172246
TI  - Obese children aged 4-6 displayed decreased fasting and postprandial ghrelin
      levels in response to a test meal.
AB  - AIM: Ghrelin is a hunger hormone that plays a role in glucose homoeostasis and
      its levels increase before a meal and decrease during and after eating. This
      study compared the fasting ghrelin and insulin levels of obese children aged 4-6
      with those of normal weight children and tested postprandial ghrelin levels in
      the obese children after a standard breakfast. METHODS: We recruited 67 children
      at Lund University Hospital from 2008 to 2011. They comprised 30 obese children
      from a weight study and 37 normal weight children receiving minor elective
      surgery. Their mean ages were 4.7 +/- 0.6 and 4.3 +/- 0.8 years, respectively.
      The obese children ate a standard breakfast, and postprandial ghrelin was
      measured after 60 minutes. RESULTS: The obese children had lower ghrelin levels
      than the controls (p < 0.01). A significant inverse relation was found between
      body mass index and fasting ghrelin levels. Obese children had significantly
      lower fasting ghrelin levels after a standard breakfast (p < 0.01), but there
      were no gender-related differences. CONCLUSION: Obese children aged 4-6 years had
      reduced ghrelin and increased insulin levels in the fasting state and
      postprandial ghrelin was suppressed, suggesting that their energy metabolism was
      already dysregulated at this young age. Early obesity interventions are
      essential.

PMID- 29172245
TI  - The Swedish Pregnancy Register - for quality of care improvement and research.
AB  - INTRODUCTION: The objective of this study was to present the Swedish Pregnancy
      Register and to explore regional differences in maternal characteristics,
      antenatal care, first trimester combined screening and delivery outcomes in
      Sweden. MATERIAL AND METHODS: The Pregnancy Register
      (www.graviditetsregistret.se) collects data on pregnancy and childbirth, starting
      at the first visit to antenatal care and ending at the follow-up visit to the
      antenatal care, which usually occurs at around 8-16 weeks postpartum. The
      majority of data is collected directly from the electronic medical records. The
      Register includes demographic, reproductive and maternal health data, as well
      information on prenatal diagnostics, and pregnancy outcome for the mother and the
      newborn. RESULTS: Today the Register covers more than 90% of all deliveries in
      Sweden, with the aim to include all deliveries within 2018. The care providers
      can visualize quality measures over time and compare results with other clinics,
      regionally and nationally by creating reports on an aggregated level or using
      case-mix adjusted Dash Boards in real time. Detailed data can be extracted after
      ethical approval for research. In this report, we showed regional differences in
      patient characteristics, antenatal care, fetal diagnosis and delivery outcomes in
      Sweden. CONCLUSIONS: Our report indicates that quality in antenatal and delivery
      care in Sweden varies between regions, which warrants further actions. The
      Swedish Pregnancy Register is a new and valuable resource for benchmarking,
      quality improvement and research in pregnancy, fetal diagnosis and delivery.

PMID- 29172247
TI  - The target of rapamycin kinase affects biomass accumulation and cell cycle
      progression by altering carbon/nitrogen balance in synchronized Chlamydomonas
      reinhardtii cells.
AB  - Several metabolic processes tightly regulate growth and biomass accumulation. A
      highly conserved protein complex containing the target of rapamycin (TOR) kinase
      is known to integrate intra- and extracellular stimuli controlling nutrient
      allocation and hence cellular growth. Although several functions of TOR have been
      described in various heterotrophic eukaryotes, our understanding lags far behind
      in photosynthetic organisms. In the present investigation, we used the model alga
      Chlamydomonas reinhardtii to conduct a time-resolved analysis of molecular and
      physiological features throughout the diurnal cycle after TOR inhibition.
      Detailed examination of the cell cycle phases revealed that growth is not only
      repressed by 50%, but also that significant, non-linear delays in the progression
      can be observed. By using metabolomics analysis, we elucidated that the growth
      repression was mainly driven by differential carbon partitioning between anabolic
      and catabolic processes. Accordingly, the time-resolved analysis illustrated that
      metabolic processes including amino acid-, starch- and triacylglycerol synthesis,
      as well RNA degradation, were redirected within minutes of TOR inhibition. Here
      especially the high accumulation of nitrogen-containing compounds indicated that
      an active TOR kinase controls the carbon to nitrogen balance of the cell, which
      is responsible for biomass accumulation, growth and cell cycle progression.

PMID- 29172248
TI  - Differential involvement of ipsilateral and contralateral spinal cord astrocyte D
      serine in carrageenan-induced mirror-image pain: role of sigma1 receptors and
      astrocyte gap junctions.
AB  - BACKGROUND AND PURPOSE: Although we have recently demonstrated that spinal
      astrocyte gap junctions mediate the development of mirror-image pain (MIP), it is
      still unclear which astrocyte-derived factor is responsible for the development
      of MIP and how its production is controlled. In the present study, we focused on
      the role of ipsilateral versus contralateral D-serine in the development of MIP
      and investigated the possible involvement of sigma1 receptors and gap junctions
      in astrocyte D-serine production. EXPERIMENTAL APPROACH: Following carrageenan
      injection, mechanical allodynia was tested at various time points to examine the
      effect of individual drugs. Immunohistochemistry and Western blot analyses were
      performed to clarify the expression levels of spinal D-serine, serine racemase,
      sigma1 receptors and connexin 43. KEY RESULTS: The expression of ipsilateral D
      serine was up-regulated during the early phase of inflammation, while
      contralateral D-serine increased during the later phase of inflammation. The
      pharmacological inhibition of D-serine during the early phase blocked the
      development of both ipsilateral and contralateral mechanical allodynia. However,
      the inhibition of D-serine during the later phase of inflammation blocked
      contralateral, but not ipsilateral mechanical allodynia. Furthermore, the
      inhibition of sigma1 receptors during the earlier phase of inflammation inhibited
      the increase in ipsilateral D-serine. Conversely, the blockade of astrocyte gap
      junctions suppressed the up-regulation of contralateral D-serine during the later
      phase of inflammation. CONCLUSION AND IMPLICATIONS: Spinal astrocyte D-serine
      plays an important role in the development of mirror-image pain. Furthermore,
      sigma1 receptors and astrocyte gap junction signalling mediate ipsilateral and
      contralateral D-serine production respectively.

PMID- 29172249
TI  - Depressive symptoms prior to and after incident cardiovascular disease and long
      term survival. A population-based study of older persons.
AB  - BACKGROUND: Depression after a cardiovascular disease event (post-CVD) is
      associated with increased mortality. However, little is known about how pre
      existing depression affects survival after CVD incidence. AIM: To evaluate
      whether depressive symptoms preceding first incident CVD (pre-CVD) affects
      survival. METHODS: From the Rotterdam Study, 6,932 persons aged 55+ and free of
      dementia and CVD completed the Center for Epidemiological Studies Depression (CES
      D) scale every 4 to 5 years from 1993. CES-D subdomains were positive affect,
      negative affect, somatic symptoms, and interpersonal affect. Persons were
      followed for mortality and CVD. RESULTS: During 15-year follow-up, 22% of
      participants suffered their first incident CVD. Pre-CVD depressive symptoms was
      not associated with mortality after adjustment for smoking status and physical
      function (HR per 10-point score: 1.05, 95%CI: 0.99-1.10). After first incident
      CVD, depressive symptoms increased. Higher post-CVD depressive symptoms was
      associated with increased mortality (HR: 1.13, 95%CI: 1.06, 1.22). The relation
      between post-CVD depressive symptoms and mortality was no longer statistically
      significant after adjustment for pre-CVD depressive symptoms. Pre-CVD and post
      CVD measures of somatic symptoms and positive affect were associated with
      mortality. CONCLUSIONS: During 15 years follow-up in community-dwelling older
      adults, the relation between higher depressive symptoms measured before first
      incident CVD and mortality was not independent of health status. Whereas, higher
      depressive symptoms measured after CVD was associated with increased mortality,
      was not independent of pre-CVD depressive symptoms. Given the associations
      observed between positive affect and mortality, positive affect may be the reason
      we observed a relation between depressive symptoms and mortality.

PMID- 29172250
TI  - High-throughput sequencing of the chloroplast and mitochondrion of Chlamydomonas
      reinhardtii to generate improved de novo assemblies, analyze expression patterns
      and transcript speciation, and evaluate diversity among laboratory strains and
      wild isolates.
AB  - Chlamydomonas reinhardtii is a unicellular chlorophyte alga that is widely
      studied as a reference organism for understanding photosynthesis, sensory and
      motile cilia, and for development of an algal-based platform for producing
      biofuels and bio-products. Its highly repetitive, ~205-kbp circular chloroplast
      genome and ~15.8-kbp linear mitochondrial genome were sequenced prior to the
      advent of high-throughput sequencing technologies. Here, high coverage shotgun
      sequencing was used to assemble both organellar genomes de novo. These new
      genomes correct dozens of errors in the prior genome sequences and annotations.
      Genome sequencing coverage indicates that each cell contains on average 83 copies
      of the chloroplast genome and 130 copies of the mitochondrial genome. Using
      protocols and analyses optimized for organellar transcripts, RNA-Seq was used to
      quantify their relative abundances across 12 different growth conditions. Forty
      six percent of total cellular mRNA is attributable to high expression from a few
      dozen chloroplast genes. RNA-Seq data were used to guide gene annotation, to
      demonstrate polycistronic gene expression, and to quantify splicing of psaA and
      psbA introns. In contrast to a conclusion from a recent study, we found that
      chloroplast transcripts are not edited. Unexpectedly, cytosine-rich
      polynucleotide tails were observed at the 3'-end of all mitochondrial
      transcripts. A comparative genomics analysis of eight laboratory strains and 11
      wild isolates of C. reinhardtii identified 2658 variants in the organellar
      genomes, which is 1/10th as much genetic diversity as is found in the nucleus.

PMID- 29172251
TI  - On computational fluid dynamics models for sinonasal drug transport: Relevance of
      nozzle subtraction and nasal vestibular dilation.
AB  - Generating anatomically realistic 3-dimensional (3D) models of the human
      sinonasal cavity for numerical investigations of sprayed drug transport presents
      a host of methodological ambiguities. For example, subject-specific radiographic
      images used for 3D reconstructions typically exclude spray bottles. Subtracting a
      bottle contour from the 3D airspace and dilating the anterior nasal vestibule for
      nozzle placement augment the complexity of model building. So we explored the
      question: how essential are these steps to adequately simulate nasal airflow and
      identify the optimal delivery conditions for intranasal sprays? In particular, we
      focused on particle deposition patterns in the maxillary sinus, a critical target
      site for chronic rhinosinusitis. The models were reconstructed from postsurgery
      computed tomography scans for a 39-year-old Caucasian male, with chronic
      rhinosinusitis history. Inspiratory airflow patterns during resting breathing are
      reliably tracked through computational fluid dynamics-based steady-state laminar
      viscous modeling, and such regimes portray relative lack of sensitivity to inlet
      perturbations. Consequently, we hypothesized that the posterior airflow transport
      and the particle deposition trends should not be radically affected by the nozzle
      subtraction and vestibular dilation. The study involved 1 base model and 2
      derived models; the latter 2 with nozzle contours (2 different orientations)
      subtracted from the dilated anterior segment of the left vestibule. We analyzed
      spray transport in the left maxillary sinus for multiple release conditions.
      Similar release points, localized on an approximately 2 mm * 4.5 mm contour,
      facilitated improved maxillary deposition in all 3 test cases. This suggests
      functional redundancy of nozzle insertion in a 3D numerical model for identifying
      the optimal spray release locations.

PMID- 29172252
TI  - Prospects on the evolutionary mitogenomics of plants: A case study on the olive
      family (Oleaceae).
AB  - The mitogenome is rarely used to reconstruct the evolutionary history of plants,
      contrary to nuclear and plastid markers. Here, we evaluate the usefulness of
      mitochondrial DNA for molecular evolutionary studies in Oleaceae, in which cases
      of cytoplasmic male sterility (CMS) and of potentially contrasted organelle
      inheritance are known. We compare the diversity and the evolution of
      mitochondrial and chloroplast genomes by focusing on the olive complex and
      related genera. Using high-throughput techniques, we reconstructed complete
      mitogenomes (ca. 0.7 Mb) and plastomes (ca. 156 kb) for six olive accessions and
      one Chionanthus. A highly variable organization of mitogenomes was observed at
      the species level. In olive, two specific chimeric genes were identified in the
      mitogenome of lineage E3 and may be involved in CMS. Plastid-derived regions
      (mtpt) were observed in all reconstructed mitogenomes. Through phylogenetic
      reconstruction, we demonstrate that multiple integrations of mtpt regions have
      occurred in Oleaceae, but mtpt regions shared by all members of the olive complex
      derive from a common ancestor. We then assembled 52 conserved mitochondrial gene
      regions and complete plastomes of ten additional accessions belonging to tribes
      Oleeae, Fontanesieae and Forsythieae. Phylogenetic congruence between topologies
      based on mitochondrial regions and plastomes suggests a strong disequilibrium
      linkage between both organellar genomes. Finally, while phylogenetic
      reconstruction based on plastomes fails to resolve the evolutionary history of
      maternal olive lineages in the Mediterranean area, their phylogenetic
      relationships were successfully resolved with complete mitogenomes. Overall, our
      study demonstrates the great potential of using mitochondrial DNA in plant
      phylogeographic and metagenomic studies.

PMID- 29172253
TI  - Transcriptome profiling of sorted endoreduplicated nuclei from tomato fruits: how
      the global shift in expression ascribed to DNA ploidy influences RNA-Seq data
      normalization and interpretation.
AB  - As part of normal development most eukaryotic organisms, ranging from insects and
      mammals to plants, display variations in nuclear ploidy levels resulting from
      somatic endopolyploidy. Endoreduplication is the major source of endopolyploidy
      in higher plants. Endoreduplication is a remarkable characteristic of the fleshy
      pericarp tissue of developing tomato fruits, where it establishes a highly
      integrated cellular system that acts as a morphogenetic factor supporting cell
      growth. However, the functional significance of endoreduplication is not fully
      understood. Although endoreduplication is thought to increase metabolic activity
      due to a global increase in transcription, the issue of gene-specific ploidy
      regulated transcription remains open. To investigate the influence of
      endoreduplication on transcription in tomato fruit, we tested the feasibility of
      a RNA sequencing (RNA-Seq) approach using total nuclear RNA extracted from
      purified populations of flow cytometry-sorted nuclei based on their DNA content.
      Here we show that cell-based approaches to the study of RNA-Seq profiles need to
      take into account the putative global shift in expression between samples for
      correct analysis and interpretation of the data. From ploidy-specific expression
      profiles we found that the activity of cells inside the pericarp is related both
      to the ploidy level and their tissue location.

PMID- 29172254
TI  - The role of nonsteroidal anti-inflammatory drugs intramuscular injection in the
      development and severity of deep soft tissue infection in mice.
AB  - The aim of this study was to determine the role of nonsteroidal anti-inflammatory
      drugs (NSAID) injection on the severity of local infection and the effect on the
      progression of soft tissue infection (STI).The mouse model of STI with Group A
      streptococcus (GAS) was developed and treated with diclofenac sodium (DS)
      intramuscularly. Mice were divided into five groups: administered DS for 48 h
      before GAS (Group 1), GAS-DS and maintained DS for 48 h (Group 2), DS for 48 h
      (Group 3), GAS on zero time (Group 4), and control (Group 5). In vitro, a high
      concentration (40 mg/L) of DS inhibited GAS growth, whereas a lower concentration
      (0.4 mg/L) was not effective. Sepsis was observed in animals with DS and GAS
      inoculation (group 1 and 2). Group 4 had statistically significant higher
      bacterial load than groups 1 and 2. All groups had a higher inflammation rate
      than the control group. The median of TNF-alpha and mean IL-6 in the groups 1, 2,
      and 4 was significantly higher than those in the control group. Even if the
      animals that were treated with DS injection prior to the GAS inoculation had
      similar inflammation score, similar cytokine levels and low bacterial load in the
      tissue, they had a rather high rate of sepsis. In conclusion, DS injection prior
      to bacterial inoculation might predispose to bacteremia and sepsis.

PMID- 29172255
TI  - Relationship between deterioration of glycated hemoglobin-lowering effects in
      dipeptidyl peptidase-4 inhibitor monotherapy and dietary habits: Retrospective
      analysis of Japanese individuals with type 2 diabetes.
AB  - The present study was designed to assess possible relationships between
      deterioration of the glycated hemoglobin (HbA1c)-lowering effects in dipeptidyl
      peptidase-4 inhibitor (DPP4i) monotherapy and macronutrient intake among
      individuals with type 2 diabetes. Type 2 diabetes patients who began and
      continued DPP4i monotherapy without any prescription change for 1 year were
      retrospectively stratified into two groups: (i) patients who maintained their
      HbA1c levels during the 0.5- to 1-year period after DPP4i initiation (group A,
      DeltaHbA1c [1-0.5 year] <0.4%, n = 53); and (ii) those whose HbA1c levels
      increased [group B, DeltaHbA1c (1-0.5 year] >=0.4%, n = 10). Group B had
      significantly higher DeltaHbA1c (1-0.5 year), Deltabodyweight (1-0.5 year) and
      fat intake, especially of saturated and monounsaturated fats; the carbohydrate
      and protein intake were similar between groups. Multiple regression analyses
      showed that fat intake, especially saturated fat intake, was significantly
      correlated with DeltaHbA1c (1-0.5 year). Thus, dietary habits, especially
      saturated fat intake, might well contribute to deterioration of the HbA1c
      lowering effects in DPP4i monotherapy.

PMID- 29172256
TI  - UICC-ARO Symposium at the UICC 2016 World Cancer CongressHow Can We Mobilize
      Action to Realize UHC in Asia?
AB  - The 2016 World Cancer Congress, organised by UICC, was held in Paris in November
      2016, under the theme "Mobilizing action - Inspiring Change." As part of Track 4
      presentations on the theme of "Strengthening cancer control: optimizing outcomes
      of health systems," UICC-Asian Regional Office (UICC-ARO) held a symposium to
      discuss the issue of mobilizing action to realize UHC in Asia. Introducing the
      symposium, Hideyuki Akaza noted that universal health coverage (UHC) is included
      in the Sustainable Development Goals and one of the key issues for achieving UHC
      will be how to balance patient needs with the economic burden of cancer. Speakers
      from Japan and Indonesia addressed various issues, including the current status
      and challenges for medical economic evaluation in Asia, the importance of
      resource stratification, prospects for precision medicine, and the outlook for
      cancer control and UHC in developing and emerging countries in Asia. Key issues
      raised included how to respond to the rising costs of treating cancer as new and
      increasingly expensive drugs come to the market. Speakers and participants noted
      that health technology assessment programs are being developed around Asia in
      order to evaluate the cost-effectiveness of drugs in the face of budgetary
      constraints within increasingly pressurized national health systems. The
      importance of screening and early detection was also noted as effective means
      that have the potential to reduce reliance on expensive drugs for advanced
      cancers. The symposium was chaired jointly by Hideyuki Akaza and Shinjiro Nozaki
      (WHO Kobe Centre).

PMID- 29172257
TI  - Clinicopathological Significance of MTA 1 Expression in Patients with Non-Small
      Cell Lung Cancer: A Meta-Analysis
AB  - Background: Metastasis associated gene 1(MTA1) is one of the most deregulated
      molecules in human cancer andleads to cancer progression and metastasis. We
      performed a meta-analysis to determine the correlations between MTA1expression
      and the clinicopathological characteristics of non-small cell lung cancer
      (NSCLC). Methods: We searchedPubMed, Springer, Science Direct, Google Scholar and
      China National Knowledge Infrastructure (CNKI) for relevantarticles. For
      statistical analyses, we used R3.1.1 software. The fixed or random effects model
      was employed based onthe results of the statistical test for homogeneity.
      Results: Seven studies involving 660 NSCLC patients were included.The proportion
      of MTA1 overexpression with 95% confidence interval (95% CI) was 0.53(95%CI: 0.43
      0.62) in NSCLCpatients; 0.47(95%CI: 0.40-0.55) in age <60 years and 0.52(95%CI:
      0.34-0.70) in age >=60 years; 0.5(95%CI: 0.41-0.62) in males and 0.51(95%CI: 0.39
      0.62) in females; 0.59(95%CI: 0.48-0.69) in squamous cell carcinoma (SC)
      and0.57(95%CI: 0.46-0.67) in adenocarcinoma (AC); 0.39(95%CI: 0.23-0.56) in well
      differentiated tumors, 0.44(95%CI:0.37-0.51) in moderately differentiated tumors
      and 0.55(95%CI: 0.37-0.51) in poorly differentiated tumors; 0.48(95%CI:0.36-0.60)
      in clinical grade (III-IV) NSCLC and 0.75 (95%CI: 0.69-0.81) in clinical grade (I
      II) NSCLC; 0.58(95%CI:0.45-0.71) in T Stage (T1/T2) NSCLC; 0.68(95%CI: 0.49-0.82)
      in NSCLC patients with lymph node positivity and0.51(95%CI: 0.43-0.58) in NSCLC
      patients with lymph node negativity. Conclusions: These results indicated
      thatMTA1 might be a valuable biomarker in the diagnosis of NSCLC. MTA1
      overexpression was significantly associatedwith age >=60 years, gender,
      histopathological type, clinical grade (I-II), T stage (T1/T2) and lymph node
      positivity inNSCLC patients.

PMID- 29172258
TI  - Dual Function of Gold Nanoparticles in Synergism with Mitoxantrone and Microwave
      Hyperthermia Against Melanoma Cells
AB  - Background: This study was performed to evaluate any synergetic effects of
      mitoxantrone (MX) and goldnanoparticles (GNPs) as dual therapeutic approach,
      along with microwave (MW) hyperthermia for melanomacancer. Methods: Various tests
      were performed on the DFW melanoma cell line in the presence of MX and
      differentconcentrations of GNPs, with and without MW irradiation. MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-iphenyltetrazoliumbromide] assays were conducted to
      evaluate the effectiveness of the used therapeutic methods in terms of cell
      survival.Relative lethal synergism (RLS) was calculated as the ratio of cell
      death following hyperthermia in the presence of atreatment agent to that after
      applying hyperthermia in the absence of the same treatment agent. Results:
      Results showedMX and GNPs under MW irradiation to provide maximum cell death (P <
      0.001 compared to the other groups). Themean RLS for MW hyperthermia along with
      the MX-GNP combination was 4.14, whereas in the absence of GNP thevalue for MX
      chemotherapy was 0.94. Conclusion: MX chemotherapy in the presence of different
      concentrations ofGNP did not alter cell survival as compared to in its absence.

PMID- 29172259
TI  - Anthocyanins from the Fruit of Vitis Coignetiae Pulliat Inhibit TNF-Augmented
      Cancer Proliferation, Migration, and Invasion in A549 Cells
AB  - Objective: Anthocyanins belong to a class of flavonoids, exhibiting antioxidant
      and anti-inflammatory actions havebeen reported to have anti-cancer effects.
      Here, we investigated whether anthocyanins can inhibit cancer cell
      proliferation,invasion, and angiogenesis in human lung cancer A549 cells, which
      are critically involved in cancer metastasis. Methods:We used anthocyanins from
      fruits of Vitis coignetiae Pulliat (AIMs) which has been used in Korean folk
      medicine forthe treatment of inflammatory diseases and cancers. We have performed
      cell proliferation assays, cell invasion assay,gelatin zymography, wound healing
      assay and western blotting to examine whether anthocyanins can inhibit cancercell
      proliferation, invasion, and angiogenesis in A549 cells. Result: AIMs did not
      inhibit cancer cell proliferation onA549 cells. Also, AIMs suppressed cancer
      migration, and invasion by supressing MMP-2 and MMP-9 expression.The Immuno
      blotting results also revealed that AIMs suppressed the proteins involved in
      cancer proliferation (COX-2, C-myc, cyclin D1), migration and invasion (MMP-2,
      MMP-9), anti-apoptosis (XIAP, and c-IAP2), adhesion andangiogenesis (ICAM-1,
      VEGF). Conclusion: This study demonstrates that the anthocyanins isolated from
      fruits ofVitis coignetiae Pulliat inhibit cancer proliferation, cancer migration,
      and invasion that is involve in cancer-metastasis.This study provides evidence
      that AIMs might have anti-cancer effects on human lung cancer.

PMID- 29172260
TI  - The Lys469glu/K469E Polymorphism of the Inflammatory Gene Intercellular Adhesion
      Molecule-1 Lacks any Apparent Role in the Polycystic Ovary Syndrome in Kashmiri
      Women: A Case Control Study
AB  - Background: Polycystic ovary syndrome (PCOS), associated with a state of low
      grade chronic inflammation,depends on multiple genetic and environmental factors.
      Elevated levels of inflammatory markers including intercellularadhesion molecule
      1 (ICAM-1) have been demonstrated in affected women. Recent evidence indicates a
      significantlinkage between chromosome 19p13 loci and multifactorial diseases that
      have an inflammatory component. The aim ofthis study was to assess the possible
      association of the lys469glu (K469E) polymorphism of the ICAM-1 gene locatedon
      chromosome 19p13 with risk of PCOS in Kashmiri women. Material and Methods: The
      K469E single nucleotidepolymorphism (SNP) was analysed with DNA from peripheral
      blood leukocytes of 220 PCOS cases and 220 agematched non-PCOS healthy controls
      using PCR-RFLP. Results: Genotypic frequencies in cases were found to be
      32(14.5%) for EE, 98 (44.5%) for KE, and 90 (40.9%) for KK, with 130 (59.1%) for
      the KE+EE genotypes comparedto healthy control values of 29 (13.2%) for EE, 113
      (51.4%) for KE, 78 (35. 5%) for KK and 142 (64.5%) for KE+EEcombined.The odds
      ratios for the EE, KE and KE:EE genotypes were 0.95(95% CI= 0.53-1.71)[p= 0.88],
      0.75(95%CI= 0.50-1.12)[p =0.168] and 0.79 (95% CI =0.53-1.16) [p = 0.23], no
      statistically significant differences being foundbetween cases and controls (chi2
      =2.07; p=0.35). Conclusion: In conclusion, there was no apparent significant
      influenceof the K469E polymorphism on risk of PCOS, or any clinical or laboratory
      parameters.

PMID- 29172261
TI  - Knowledge of Evidence-Based Cancer Risk Factors Remains Low Among New Zealand
      Adults: Findings from Two Cross-Sectional Studies, 2001 and 2015
AB  - Objective: Cancer risk reduction messages are a part of cancer control efforts
      around the world. The complex realityis that risk factors differ for different
      types of cancer, making clear communication of desired behavioural changes
      moredifficult. This study aims to describe awareness of risk factors for breast,
      bowel, cervical, prostate and lung cancer andcutaneous melanoma among New
      Zealanders in 2014/15 and identify changes in awareness since 2001. Methods:
      Twonational telephone surveys, the first (CAANZ01) conducted in 2001, included
      438 adults (231 females and 207 males,64% response rate). The second, conducted
      in 2014/15 (CAANZ15), included 1064 adults (588 females and 476 males,64%
      response rate). Results: In 2014/5, most participants could identify evidence
      based risk factors for lung cancerand melanoma. In contrast, many participants
      were unable to name any risk factors (evidence-based or otherwise) forbowel
      (34.8%), breast (48.8%), cervical (53.9%) and prostate cancer (60.9%). Between
      2001 and 2014/5 there wereincreases in the proportion of individuals identifying
      sunbeds as increasing melanoma risk, and alcohol consumption andfamily history as
      increasing risk for bowel and breast cancer. Conclusions: Effective communication
      of risk informationfor specific cancers remains a challenge for cancer control.
      Although some positive changes in awareness over the 14year period were observed,
      there remains substantial room for progressing awareness of evidence-based risk
      factors.

PMID- 29172263
TI  - Predicting Intention Perform Breast Self-Examination: Application of the Theory
      of Reasoned Action
AB  - Objective: The present study aimed to examine the applicability of the theory of
      reasoned action to explain intentionto perform breast self-examination (BSE).
      Methods: A questionnaire was constructed to collect data. The hypothesiswas
      tested in two steps. First, to assess the strength of the correlation among the
      constructs of theory of reasoned action(TRA), Pearson's product moment
      correlations were applied. Second, multivariate relationships among the
      constructswere examined by performing hierarchical multiple linear regression
      analysis. Result: The findings supported the TRAmodel, explaining 45.8% of the
      variance in the students' BSE intention, which was significantly correlated with
      attitude(r = 0.609, p = 0.000) and subjective norms (r = 0.420, p =0 .000).
      Conclusion: TRA could be a suitable model to predictBSE intentions . Participants
      who believed that doing BSE regularly is beneficial for early diagnosis of breast
      cancerand also believed that their significant referents think that doing BSE
      would significantly detect breast cancer earlier,were more likely to intend to
      perform BSE regularly. Therefore, the research findings supported the conclusion
      thatpromoting the importance of BSE at the community/social level would enhance
      individuals to perform BSE routinely.

PMID- 29172262
TI  - Modulatory Effects of Chemoradiation on Angiogenic Factors and Laminin in
      Cervical Cancer: Link with Treatment Response
AB  - Objective: Carcinoma of the uterine cervix is either the first or second most
      common malignancy in Indian women,depending on the registry. Tumor growth and
      metastasis primarily are determined by angiogenesis and parametersof the
      molecular environment including extracellular matrix elements, growth factors and
      cytokines. Effects ofchemo-irradiation on biomarkers like vascular endothelial
      growth factor (VEGF), angiopoietin-2 (Ang-2) and lamininin patients with
      carcinoma cervix therefore need to be explored. Methods: Circulatory and mRNA
      levels of VEGF,Ang-2 and laminin in patients with stage III carcinoma cervix
      (n=40) were compared with those of normal healthywomen (n=20). Measurement was
      prior to treatment, and after chemotherapy and teleradiation, using high
      sensitivityELISA kits and Q-PCR. Clinical response was evaluated as per WHO
      criteria and was assessed for correlation with thebiochemical markers. Results:
      Levels of all the studied molecules were significantly (p<0.001) higher in
      patients than incontrols. After treatment significant decline (p<0.001) was
      noted. Out of 40 patients, 33 were complete responders and7 were non-responders
      on clinical assessment. On comparison of before and after treatment levels of
      these moleculescomplete responders showed significant decline whereas non
      responders showed non-significant decrease. Follow-upof the responders for 3
      years, revealed 28 of 33 patients to still be disease free, the other 5
      demonstrating recurrence.Conclusions: Higher levels of angiogenic factors along
      with laminin indicate roles played in disease progression aidingangiogenesis.
      These markers may serve as useful tools in post treatment disease mapping, for
      which available imagingmethods may not provide a true picture.

PMID- 29172264
TI  - Different Sources of Dignity-Related Distress in Women Receiving Chemotherapy for
      Breast Cancer
AB  - Background: Identification of different sources of dignity-related distress
      experienced by people nearing the end oflife may help nurses to provide better
      care services. This study was conducted to determine sources of dignity
      relateddistress from the perspective of women with breast cancer undergoing
      chemotherapy. Materials and Methods: Inthis cross sectional study, the
      participants comprised 207 women with breast cancer undergoing chemotherapy
      inchemotherapy clinics in hospitals of Tehran, Iran. The Cronbach's coefficient
      alpha for the PDI was 0.76. Validityof PDI by confirmatory factor analysis shows
      that the comparative Fit Index of this instrument is 0.96 and so it isappropriate
      for application in different setting. Data were analyzed by Stata version 13.
      Results: Patients were mostlyconcerned about the distress caused by disease
      symptoms (mean; 2.4061, S.D.; 0.96), followed by existential distress(mean;
      1.8784, S.D.; 0.75), peace of mind (mean; 1.871, S.D.; 0.77), dependence (mean;
      1.8647, S.D.; 0.98), andsocial support (mean; 1.4097, S.D.; 0.99), respectively,
      in order of highest scores. Conclusion: Considering that thepatients were mostly
      concerned about the distress caused by disease symptoms, followed by existential
      distress, peaceof mind, dependency, and social support, it seems necessary to
      take further measures toward addressing these issues.

PMID- 29172265
TI  - SNPs in the Insulin-Like Growth Factor Gene and Obesity Impact on Colorectal
      Cancer in Egyptians
AB  - Background and aims: The insulin pathway may play a role in development of
      colorectal cancer (CRC). Inthis study, we investigated associations between CRC
      and obesity in Egyptians with reference to single nucleotidepolymorphisms (SNPs)
      in the insulin-like growth factor-1 (IGF-I) gene. We also studied serum levels of
      IGF-1inEgyptian CRC patients with different BMI values. Methods: This prospective
      study included 66 CRC patients and30 healthy individuals, for whom body mass
      index (BMI) was estimated, patients and controls being categorized intooverweight
      or obese in one group and average weight in the other. Serum levels of IGF-1 were
      assessed by ELISA andSNPs in the IGF-I gene at rs6214C/T, rs6220 T/C and rs35767
      C/T were examined by PCR- RFLP. Results: Serumlevels of IGF-1 were significantly
      lower in both CRC average weight and overweight cases. IGF-1 could
      negativelypredict CRC at a cut-off of 154 ng/ml with 87.5% sensitivity and 72.6
      specificity. IGF-1 rs6214 CT and TT (T allele)genotypes were associated with a
      significantly increased risk of CRC. Univariate logistic regression showed that
      CRCrisk significantly decreases by 0.14 for each one unit increase in IGF1.
      Conclusion: BMI could be considered as effectmodifier for CRC risk. IGF-1 SNP
      rs6214 (TT and CT) are significantly associated with risk regardless of the BMI.

PMID- 29172266
TI  - Dosimetric Validation of Volumetric Modulated Arc Therapy (VMAT) Using AAPM TG
      119 Benchmark Plans in an Upgraded CLINAC 2100CD for Flattening Filter Free (FFF)
      Photon Beams
AB  - Background: Recently we have upgraded our Varian Clinac 2100CD with a 6MV FFF
      beam, this upgrade beingthe first of its kind in our country. Even though the
      dosimetric characteristics of FFF beams have been reported both inexperimental
      and Monte Carlo studies, application in planning and delivery is complex. The aim
      of this study was tovalidate the commissioning of upgraded FFF beams
      dosimetrically using AAPM TG-119 bench mark plans for VMATand to make a
      comparison with IMRT plans for both flattened filtered and FFF beams. Materials
      and Methods: AAPMTG-119 proposes a set of test clinical cases for testing the
      accuracy of IMRT planning and delivery systems. For theseclinical cases we
      generated four treatment plans using IMRT FF, IMRT FFF, VMAT FF and VMAT FFF on a
      VarianClinac 2100CD machine equipped with a millennium 120 MLC in Eclipse
      treatment planning system. Dose prescriptionand planning objectives were set
      according to the TG-119 goals and plans were scored based on planning
      objectives.Plans were compared using dose coverage, the conformity index and the
      homogeneity index. Point doses were measuredat points recommended by TG-119 using
      a CC13 ion chamber. Planar dosimetry was accomplished using Imatrix andgamma
      evaluation was conducted using Omnipro IMRT software. Results: Dose distributions
      of FFF beam basedplans were comparable to FF plans for both IMRT and VMAT. Our
      planning results matched TG-119 planning results.Measured point doses were within
      +/-2% of planned doses and planar dosimetry gamma values were <1 for >95% ofdata
      points for all plans. Conclusion: We found a reduction of 40% treatment time for
      FFF against FF beams for slidingwindow IMRT. Upgraded FFF beams were in good
      agreement with TG-119 benchmark plans and goals.

PMID- 29172267
TI  - Breast Cancer Risk Assessment Using the Gail Model and It's Predictors in Saudi
      Women
AB  - Background: The Gail Model has been widely implemented in developed and
      developing countries and is consideredto be the best available instrument to
      estimate breast cancer (BC) risk for early prevention. Objective: The goals ofthe
      study were to determine five-year and lifetime BC risks and to assess BC
      predictors among female Saudi teachersusing the Gail model. Methods: A cross
      sectional study with convenience sampling was conducted among 180 femaleSaudi
      secondary school teachers. The Gail model was used to evaluate the five-year and
      lifetime risks of developingBC. Included were a one-day 24-hour recall to assess
      daily serving sizes and food groups for food intake and questionsregarding daily
      exercise, BMI, and demographic data. Result: The mean age of the teachers was
      41+/-7.2 years, witha 0.87+/-0.93 mean for the five-year risk and a 9.6+/-5.4
      mean lifetime risk of developing BC. According to the generallinear model, the BC
      risk predictors were age, age at menarche, age at first pregnancy, family
      history, BMI, fruit andvegetable intake, and meat intake. Conclusion: The present
      study provided new information regarding the potentialfactors for five-year and
      lifetime invasive BC risk among Saudi women. Moreover, we could confirm that the
      Gailmodel is an appropriate BC risk assessment tool for Saudi women for early
      prevention, particularly among women athigh risk of BC.

PMID- 29172268
TI  - Effect of Targeted Therapy With Pazopanib on Expression Levels of Transcription,
      Growth Factors and Components of AKT/m-TOR Signaling Pathway in Patients with
      Renal Cell Carcinoma
AB  - Background: The effect of the targeted therapy on cancer molecular markers
      remains currently unknown. Theaim of the study was to investigate the expression
      and content of transcription, growth factors and components of theAKT/m-TOR
      signaling pathway in kidney cancer patients before and after targeted therapy
      with pazopanib. Methods:A total of 157 patients with renal cell carcinoma were
      enrolled into the study. The level of mRNA expression wasinvestigated by real
      time PCR, and the contents of transcription and growth factors, as well as the
      levels of AKT/m-TOR signaling pathway components were determined by ELISA and
      Western blotting. Results: Targeted therapy withpazopanib resulted in a 3.1-fold
      decrease in HIF-2alpha expression that was accompanied by a reduction in the
      levels ofNF-kappaB p65 and p50, HIF-1alpha and CAIX. The levels of GSK-3beta and
      AKT mRNA were increased; however, the levelsof corresponding proteins remained
      low. The targeted therapy with pazopanib did not influence the level of
      PTENphosphatase. A 1.9-fold increase in the level of p70 S6 (S371) was observed
      after therapy. Conclusion: The efficacy oftyrosine kinase inhibitors is
      associated with the changes in the angiogenic factors. Molecular characteristics
      of cancercould determine markers of disease progression as well as potential
      targets for anticancer therapies

PMID- 29172269
TI  - Positive Impact of Social Media Use on Depression in Cancer Patients
AB  - Objective: The focus of attention was the prevalence of depression among cancer
      patients using social networks.An attempt was made to determine if social media
      could help cancer patients overcome their stress and depression,causes of serious
      emotional and mental problems for them and their families. Methods: To ascertain
      the prevalenceof depression among cancer patients with reference to use of social
      networks, 316 cancer patients in the Associationof Cancer Patients and cancer
      related centers in Tehran at 2015 were evaluated. Depression was measured using
      theBeck Depression Inventory. Data were analyzed by the Chi-square test with SPSS
      software. Results: Using the Beckcriteria, 61% (N=192) of patients were
      depressed. Interestingly, a significant difference was observed between
      depressionin users and non-users of social networks (p=0.001), 33.9% and 66.1%
      being affected, respectively. Conclusion:These results verified a high incidence
      of depression in cancer patients, but a beneficial effect of social network
      use.Therefore access to social networks should be promoted for prevention and
      amelioration of depression. Moreover, itis recommended that particular attention
      be paid to the patient sex and educational level in designing counseling
      andpsychological skill training programs.

PMID- 29172270
TI  - 18-Fluorodeoxy-Glucose Positron Emission Tomography- Computed Tomography (18-FDG
      PET/CT) for Gross Tumor Volume (GTV) Delineation in Gastric Cancer Radiotherapy
AB  - Purpose: Evaluation of the 18-fluorodeoxy-glucose positron emission tomography
      computed tomography (18-FDGPET/CT) for gross tumor volume (GTV) delineation in
      gastric cancer patients undergoing radiotherapy. Methods: In thisstudy, 29
      gastric cancer patients (17 unresectable and 7 inoperable) were initially
      enrolled for radical chemoradiotherapy(45Gy/25 fractions + chemotherapy based on
      5 fluorouracil) or radiotherapy alone (45Gy/25 fractions) with planningbased on
      the 18-FDG-PET/CT images. Five patients were excluded due to excess blood glucose
      levels (1), false-negativepositron emission tomography (1) and distant metastases
      revealed by 18-FDG-PET/CT (3). The analysis involvedmeasurement of metabolic
      tumor volumes (MTVs) performed on PET/CT workstations. Different threshold levels
      ofthe standardized uptake value (SUV) and liver uptake were set to obtain MTVs.
      Secondly, GTVPET values were derivedmanually using the positron emission
      tomography (PET) dataset blinded to the computed tomography (CT)
      data.Subsequently, GTVCT values were delineated using a radiotherapy planning
      system based on the CT scans blinded tothe PET data. The referenced GTVCT values
      were correlated with the GTVPET and were compared with a conformalityindex (CI).
      Results: The mean CI was 0.52 (range, 0.12-0.85). In 13/24 patients (54%), the
      GTVPET was larger thanGTVCT, and in the remainder, GTVPET was smaller. Moreover,
      the cranio-caudal diameter of GTVPET in 16 cases(64%) was larger than that of
      GTVCT, smaller in 7 cases (29%), and unchanged in one case. Manual PET
      delineation(GTVPET) achieved the best correlation with GTVCT (Pearson correlation
      = 0.76, p <0.0001). Among the analyzedMTVs, a statistically significant
      correlation with GTVCT was revealed for MTV10%SUVmax (r = 0.63; p = 0.0014),
      MTVliv(r = 0.60; p = 0.0021), MTVSUV2.5 (r = 0.54; p = 0.0063); MTV20%SUVmax (r =
      0.44; p = 0.0344); MTV30%SUVmax (r = 0.44;p = 0.0373). Conclusion: 18-FDG-PET/CT
      in gastric cancer radiotherapy planning may affect the GTV delineation.

PMID- 29172271
TI  - Association between ERCC1 Polymorphism and the Risk and Clinicopathological
      Features of Breast Cancer in Thai Women in the Lower Northeastern Region
AB  - Background: Breast cancer is a major public health problem around the world,
      including Thailand and it hasthe highest ranking among female cancer. Currently,
      the diversity or polymorphism of ERCC1 gene (excision repaircross-complementary
      group 1 gene or ERCC1) was reported to associate with an increased risk of breast
      cancer.This study aims to investigate the relationship between ERCC1 polymorphism
      and the breast cancer risk in the lowernortheastern region women of Thailand.
      Materials and Methods: One hundred fifty one samples from breast cancerpatients
      and 120 samples from healthy control group were analysed. Genomic DNA was
      extracted from white bloodcell of all samples. The real-time polymerase chain
      reaction (qPCR) was used to demonstrate genetic polymorphismof ERCC1. Results:
      The results showed that the ERCC1 rs11615 polymorphism variant AG was associated
      with anincreased risk of breast cancer. This study demonstrated that the
      frequency of ERCC1 rs11615 in patients with breastcancer was higher than healthy
      control group. The ERCC1 polymorphism variant AG carrier presented 3.53-folds
      highrisk of breast cancer [odds ratio (OR) = 3.53, 95% CI = 1.61-7.74, P =
      0.001]. In addition, when age, menopause period,number of child, smoking and
      alcohol drinking were adjusted, the ERCC1 rs11615 variant AG carrier was
      associatedwith increased breast cancer risk to 3.97 folds, with OR = 3.79, 95% CI
      = 1.62-8.84, P = 0.002. Conclusions: Thisstudy showed that ERCC1 rs11615 genotype
      AG was associated with breast cancer risk in the lower northeasternregion women
      of Thailand.

PMID- 29172272
TI  - Promoter Hypermethylation of the ATM Gene as a Novel Biomarker for Breast Cancer
AB  - Background: Breast cancer may be induced by activation of protooncogenes to
      oncogenes and in many casesinactivation of tumor suppressor genes. Ataxia
      telangiectasia mutated (ATM) is an important tumor suppressor genewhich plays
      central roles in the maintenance of genomic integrity by activating cell cycle
      checkpoints and promotingrepair of double-strand breaks of DNA. In breast cancer,
      decrease ATM expression correlates with a poor outcome;however, the molecular
      mechanisms underlying downregulation are still unclear. Promoter hypermethylation
      maycontribute in downregulation. Hence the present investigation was designed to
      evaluate promoter methylation andexpression of the ATM gene in breast cancer
      cases, and to determine links with clinical and demographic manifestations,in a
      South Indian population. Methods: Tumor biopsy samples were collected from 50
      pathologically confirmedsporadic breast cancer cases. DNA was isolated from tumor
      and adjacent non-tumorous regions, and sodium bisulfiteconversion and methylation
      specific PCR were performed using MS-PCR primers for the ATM promoter region.
      Inaddition, ATM mRNA expression was also analyzed for all samples using real-time
      PCR. Results: Fifty eight percent(58%) of cancer tissue samples showed promoter
      hypermethylation for the ATM gene, in contrast to only 4.44% ofnormal tissues (p=
      0.0001). Furthermore, ATM promoter methylation was positively associated with age
      (p = 0.01),tumor size (p=0.045) and advanced stage of disease i.e. stages III and
      IV (p =0.019). An association between promoterhypermethylation and lower
      expression of ATM mRNA was also found (p=0.035). Conclusion: We report for
      thefirst time that promoter hypermethylation of ATM gene may be useful as a
      potential new biomarker for breast cancer,especially in the relatively young
      patients.

PMID- 29172273
TI  - Sonographic Diagnosis of Tubal Cancer with IOTA Simple Rules Plus Pattern
      Recognition
AB  - Objective: To evaluate diagnostic performance of IOTA simple rules plus pattern
      recognition in predicting tubalcancer. Methods: Secondary analysis was performed
      on prospective database of our IOTA project. The patientsrecruited in the project
      were those who were scheduled for pelvic surgery due to adnexal masses. The
      patients underwentultrasound examinations within 24 hours before surgery. On
      ultrasound examination, the masses were evaluated usingthe well-established IOTA
      simple rules plus pattern recognition (sausage-shaped appearance, incomplete
      septum,visible ipsilateral ovaries) to predict tubal cancer. The gold standard
      diagnosis was based on histological findings oroperative findings. Results: A
      total of 482 patients, including 15 cases of tubal cancer, were evaluated by
      ultrasoundpreoperatively. The IOTA simple rules plus pattern recognition gave a
      sensitivity of 86.7% (13 in 15) and specificityof 97.4%. Sausage-shaped
      appearance was identified in nearly all cases (14 in 15). Incomplete septa and
      normalovaries could be identified in 33.3% and 40%, respectively. Conclusion:
      IOTA simple rules plus pattern recognitionis relatively effective in predicting
      tubal cancer. Thus, we propose the simple scheme in diagnosis of tubal cancer
      asfollows. First of all, the adnexal masses are evaluated with IOTA simple rules.
      If the B-rules could be applied, tubalcancer is reliably excluded. If the M-rules
      could be applied or the result is inconclusive, careful delineation of the
      masswith pattern recognition should be performed.

PMID- 29172274
TI  - Delay in Diagnosis and Treatment of Breast Cancer among Women Attending a
      Reference Service in Brazil
AB  - Background: Cancer is a major public health problem. Early diagnosis and
      treatment are essential for reducingmortality. This study aimed to analyze
      factors associated with delay in breast cancer diagnosis and treatment amongwomen
      attending a reference cancer service. Methods: This retrospective, cross
      sectional study was performed withdata collected from medical records and
      interviews conducted with women diagnosed with breast cancer and treatedfrom
      October 2013 to October 2014 at a cancer reference hospital in Parana, Southern
      Brazil. Results: A total of 82participants were enrolled during the study period;
      their average age was 58.2 +/- 11.5 years. The average time takenfor final
      diagnosis of breast cancer was 102.5 +/- 165.5 days. Treatment onset was delayed
      in the majority of cases, andthe average time elapsing from diagnostic biopsy to
      onset of primary treatment was 72.3 +/- 54.0 days. The odds oftreatment delay
      were higher among the women with a low educational level. Conclusions: The
      results underline theneed for proposals aimed at early detection, identification
      of risk factors and timely provision of treatment by healthmanagers that focus on
      this group.

PMID- 29172275
TI  - Interleukin-6 Genetic Variation and Susceptibility to Gastric Cancer in an
      Iranian Population
AB  - Background: Despite recent decrease in the incidence of gastric cancer, it is
      still a common type of cancer in thenorth of Iran. Many evaluations have shown
      that polymorphisms of cytokine genes like that for interleukin 6 (IL-6),which
      play important roles in regulation of the immune response, can increase the risk
      of gastric cancer. This studyexamined the role of the IL-6-174 gene polymorphism
      in susceptibility in an Iranian population. Method: GenomicDNA was extracted from
      peripheral whole blood of 100 patients and 361 healthy controls. Genotyping was
      accomplishedby the sequence-specific primer-polymerase chain reaction (SSP-PCR)
      method and statistical analyses were carriedout using Fisher's exact test.
      Frequencies of the IL-6-174 G/C genotypes were determined under co
      dominant,dominant, and recessive genetic models. Results: An association between
      the polymorphism of IL-6 -174 G/C andsusceptibility to gastric cancer was
      observed. The frequency of G allele was higher in patients (78%) than in
      controls(70.5 %) (OR=1.48, 95% CI=1.01-2.20, P=0.04). Conclusions: The high G
      allele and G/G genotype frequency inpatients compared to control subjects
      suggests that the IL-6 -174 G/C polymorphism may influence the susceptibilityto
      gastric cancer. In addition, the demographic information showed that most of the
      subjects were male (69.0%) thatgastric cancer is related to environmental
      factors.

PMID- 29172276
TI  - FLT3-ITD, NPM1, and DNMT3A Gene Mutations and Risk Factors in Normal Karyotype
      Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients in Upper Northern
      Thailand
AB  - Objective: Approximately 40-45% of AML and MDS patients have a cytogenetically
      normal karyotype (CN-AMLand CN-MDS). The frequency and types of gene mutations in
      these cases may differ among various populations.The objective of this study was
      to identify frequencies and types of FLT3-ITD, NPM1, and DNMT3A mutations,
      andassociations of them with clinical data and risk factors in CN-AML and CN-MDS
      cases in upper Northern Thailand.Methods: Bone marrow samples of 40 CN-AML and 60
      CN-MDS patients were analyzed for gene mutations bydirect sequencing. In
      addition, data for potential risk factors were obtained for comparison. Results:
      Frequencies ofFLT3-ITD, NPM1, and DNMT3A mutations were 25.0%, 17.5%, and 10.0%,
      respectively in CN-AML, but all zero inCN-MDS cases. NPM1 mutations were found at
      a median age older than the wild type (58 vs 47 years) while DNMT3Amutations were
      associated with an increase in the white blood cell count. In all patients,
      factors for the mutations ofthese three genes included age <= 60 years, and a
      history of hypertension. Conclusion: When considering mutations inonly normal
      karyotype patients, the frequency of FLT3-ITD, NPM1, DNMT3A mutations in CN-AML
      patients in upperNorthern Thailand were found to occur at lower rates than in
      Western patients and to differ from other Asian populationsincluding parts of
      Thailand. No mutations were observed in CN-MDS cases. Some types of gene
      mutations differed fromprevious studies, possibly attributable to differences in
      geography, lifestyle and genetic backgrounds. Links with age <=60 years and
      history of hypertension were found. Investigation of these three genes in an
      intermediate risk group witha normal karyotype is useful for a better
      understanding of molecular leukemogenetic steps in CN-AML and CN-MDSpatients and
      may be beneficial for planning treatment and prevention in the population of
      upper Northern Thailand.

PMID- 29172277
TI  - DNA Replication Licensing Proteins for Early Detection of Lung Cancer
AB  - Background: To identify and characterize malignant and premalignant cells in
      sputum and matched tissue sampleswith reference to expression of minichromosome
      maintenance proteins (MCM2, MCM5) and cell division cycleprotein 6 (CDC 6) and to
      assess their potential as biomarkers of premalignant and malignant lesions of the
      lung andassociations with clinicopathological features. Methods: Expression of
      MCM2, MCM5 and 6 proteins in sputumsamples and corresponding tissues was assessed
      by immunocytochemistry, and correlated with histological findings.Results: For
      characterization of malignant, metaplastic or dysplastic cells, CDC6 protein had
      the highest sensitivityof 87.7%. All the three markers together had a sensitivity
      of 94.4%. Furthermore these proteins could be employed toassess the proliferative
      potential of precancerous or atypical cells, as overexpression increasing with
      the stage of diseaseand degree of metastasis. Conclusion: The assessed markers
      can be utilized in routine cytopathology laboratoriesto supplement conventional
      morphological evaluation so that the sensitivity of sputum cytology can be
      enhanced.Potential applications in predicting the clinical behavior of lung
      lesions and predicting prognosis and survival deservefurther attention.

PMID- 29172278
TI  - P16ink4a Subcellular Expression Patterns in Colorectal Adenocarcinoma, Adenoma
      and Non-Neoplastic Tissue Samples
AB  - Background: Colorectal cancer (CRC) is one of the most common neoplasms with high
      mortality at advancedstages worldwide. Thus diagnosis of CRC at an early stage
      with sensitive molecular methods is a high priority. Theaim of this study was to
      evaluate P16ink4a subcellular expression patterns in colorectal adenocarcinoma,
      adenoma andnon-neoplastic tissue samples. Methods: A total of 137 colorectal
      formalin fixed paraffin-embedded tissue blocksfrom the pathology archives of Ali
      Ebne-Abitaleb central hospital, Zahedan, Iran, were examined in three
      groups:adenocarcinoma (n= 63), adenoma (n= 38) and non-neoplastic (n= 36). The
      subcellular expression pattern wasdetermined by immunocytochemistry. Data
      analysis was performed using Kruskal-Wallis and Fisher exact tests withthe
      significance level set as p?0.05. Results: P16ink4a subcellular localization was
      observed in three different patterns,nuclear+cytoplasmic (73.33%), cytoplasmic
      (13.33%) and nuclear (13.33%). In most samples, nuclear+cytoplasmicwas the
      predominant subcellular pattern. However, a significant difference in P16ink4a
      subcellular expression patternswas observed along the non-neoplastic, adenoma,
      adenocarcinoma sequence (p?0.001). An association with thehistological tumor type
      was also noted (p=0.021). Conclusion: Considering variation in localization of
      P16ink4a underdifferent pathological conditions, P16ink4a night be sensitive
      prognostic biomarker for benign colon lesions. Its use mayimprove strategies for
      screening, prognostic assessment and management of patients with CRC. Further
      studies arerecommended in this field.

PMID- 29172279
TI  - Anti-Vascular Endothelial Growth Factor Targeting by Curcumin and Thalidomide in
      Acute Myeloid Leukemia Cells
AB  - Acute myeloid leukemias (AMLs) are blood disorders that exhibit uncontrolled
      growth and reduction of apoptosisrates. As with other malignancies, progression
      may be result of induction and formation of new blood vessels influencedby
      disease conditions. Cancer cells produce a variety of factors which play
      important roles in angiogenesis. Vascularendothelial growth factor (VEGF) is
      critical for many malignancies, including AMLs. Curcumin, as a natural
      compound,is able to enhance apoptosis via a mechanism affecting regulatory genes.
      As a new strategy we here evaluated anti-VEGF properties of curcumin, alone and
      in combination with thalidomide, in leukemic cell lines. Growth inhibitoryeffects
      were assessed by MTT assay and apoptosis was detected by annexin/PI staining in
      U937 and KG-1 cell lines.mRNA expression levels of VEGF isoforms were evaluated
      by qRT-PCR. Curcumin inhibited proliferation and inducedapoptosis in both KG-1
      and U937 cells and this effect was stronger in combination with thalidomide. In
      KG-1 cells, thelevel of VEGF (A, B, C and D) mRNA was decreased in curcumin
      treated as compared to untreated cells. Maximumeffects were obtained at the
      concentration of 40 MUM curcumin in U937 cells. Taken together, the results
      indicate thatthe VEGF autocrine loop may have an impact on AML development and
      progression and could be considered as atherapeutic target. Thalidomide as a VEGF
      inhibitor in combination with curcumin appears to have a synergistic impacton
      inhibition of cell proliferation and promotion of apoptosis.

PMID- 29172280
TI  - Relationships of Ex-Vivo Drug Resistance Assay and Cytokine Production with
      Clinicopathological Features in the Primary Cell Culture of Thai Ovarian and
      Fallopian Tube Cancer Patients
AB  - Objective: Our goal was to determine the ex-vivo drug resistance assay, as well
      as the cytokine production, inresponse to platinum-based chemotherapy treatment
      in primary culture cells established from the tumor tissue of ovarianor fallopian
      tube carcinoma patients, and to predict the clinical responses to chemotherapy.
      Methods: Sensitivity tothe platinum-based drug was analyzed in two ovarian cancer
      cell lines and 19 tumor samples using the primary cellculture obtained from 19
      patients having ovarian or fallopian tube cancer that had undergone surgery from
      2014 to 2017.Results: Our findings in the ovarian cancer cell lines showed that
      SKOV3 cells displayed 10-fold greater resistanceto cisplatin and 5.8 times more
      resistance to carboplatin than A2780 cells. SKOV3 cells displayed platinum
      inducedIL-6 and IL-8 overproduction whereas wild type A2780 displayed no
      detectable cytokine production. Regarding theprimary cell culture obtained from
      patients, ex-vivo drug resistance assay results revealed that although extreme
      drugresistance was correlated with late stage ovarian cancer (P= 0.031), it could
      not independently predict or alter theoutcomes of patients with ovarian or
      fallopian tube cancer. No relationship was found between basal cytokine
      secretionand the clinical parameters. However, carboplatin-induced IL-6 and IL-8
      production had a significant association withthe clinical response to
      chemotherapy (P=0.016 and P=0.038 respectively). Carboplatin-induced IL-8
      overproductionwas correlated with FIGO staging III-IV (P=0.026), but no
      correlation between carboplatin-induced IL-6 and FIGOstaging (P= 0.061) was
      noted. Conclusion: These results suggest that cytokine production in response to
      platinum-basedchemotherapy in primary culture cells may be useful as a predictive
      marker for the therapeutic outcomes among ovarianor fallopian tube cancer
      patients.

PMID- 29172281
TI  - SNP rs16969968 as a Strong Predictor of Nicotine Dependence and Lung Cancer Risk
      in a North Indian Population
AB  - Background: The 15q24-25 loci contain genes (CHRNA5 and CHRNA3) encoding
      nicotinic acetylcholine receptorsubunits. We here determined for the first time
      the association of genetic variants rs16969968 and rs3743074 inCHRNA5 and CHRNA3,
      respectively, on nicotine dependence and lung cancer risk in a North Indian
      population by acase-control approach. Methods: Venous blood samples were obtained
      from 324 participants (108 lung cancer patientsand 216 healthy individuals). DNA
      was extracted and PCR amplified with primers flanking the SNPs rs16969968
      andrs3743074. Amplicons were subjected to sequencing and logistic regression was
      used to analyze association betweenvariables. Results: The risk variant SNP
      rs16969968 in both heterozygous and homozygous forms appeared to exerta
      significant effect on nicotine dependence [GA (OR=2.77) and AA (OR=2.53)]. As
      expected, smoking was stronglyassociated with lung cancer (OR= 2.62). Risk allele
      rs16969968 in CHRNA5 also showed a significant association withincreased lung
      cancer risk in our cohort, alone (OR= 4.99) and with smoking as a co-variable
      (OR= 4.28). Comparisonof our analysis with other populations suggested that
      individuals with rs16969968 risk allele in the Indian populationare more
      susceptible to lung cancer. Conclusion: Overall, the results strongly indicated
      that, in our cohort North Indianpopulation, the genetic variant rs16969968, but
      not rs3743074, is significantly associated with both nicotine dependenceand
      increased risk of lung cancer. While the results are significant, there is
      further need to increase the sample size andimprove precision of our risk
      prediction.

PMID- 29172282
TI  - Primary Locations of Malignant Melanoma Lesions Depending on Patients' Gender and
      Age
AB  - Introduction: Location of malignant melanoma lesions depends on environmental,
      genetic, sociological anddemographical factors. Available sources do not provide
      enough information on such dependencies in various populations.There is no data
      concerning the role of socio-demographic factors for the population of the
      Central and Eastern Europe.Aim: The aim of this work was to evaluate the
      anatomical location of the primary malignant melanoma lesion incorrelation to
      patients' gender and age. Material and methods: A retrospective analysis of
      medical documentationof 363 patients has been performed. The patients had been
      diagnosed with malignant melanoma and were undergoingtreatment in the years 2010
      2014 in two Polish oncologic hospitals. The subject group consisted of 199 (55%)
      femalesand 164 (45%) males. The age varied between 19 - 90 years, with the median
      of 62 years. Results: In women, themelanoma lesions seem to appear more often in
      their lower extremities, while in case of men such lesions seem to bemore often
      on their torsos. In both cases, the difference was statistically significant
      (p<0.01 When the specific locationsare considered in women the lesions were more
      often located on their shins (p<0.01), whereas for men the lesions werelocated on
      their backs (p<0.01). It has been observed that there is dependency between
      lesion localization and age ofpatients. The lesions located on heads and necks
      were most common in older patients, and the lesions located in lowerextremities
      were most common in younger ones. Conclusion: Differences in location of
      malignant melanoma lesionsmay be due to either genetic or environmental reasons.
      It is often emphasized in literature that correlation between thesocio
      demographic factors and the process of oncogenesis requires intensive research.
      In our work, we have tried to fillthis gap for the population of Central and
      Eastern Europe to determine the exact epidemiology of this kind of cancer.This
      knowledge may be then used for developing cancer prevention methods specific to
      gender and age.

PMID- 29172283
TI  - Repair Index in Examination of Nuclear Changes in the Buccal Mucosa of Smokers: A
      Useful Method for Screening of Oral Cancer
AB  - Background: Smoking is one of the major risk factors for cancers, especially in
      the oral cavity. Nuclear changesoccur in the early stages of cancer. The aim of
      this study was therefore to investigate nuclear changes and calculate a"repair
      index" for the buccal mucosa of smokers. Material and Methods: This historical
      cohort study was conductedby selecting samples including smokers and non-smokers.
      In addition, the smoker group were divided into 2 subgroupswith a smoking history
      of >10 and <=10 years. Buccal mucosa smears were obtained and Papanicolaou
      staining wasemployed to detect nuclear changes. Micronuclei, karyorrhexis and
      karyolysis were assessed and eventually a repairindex was calculated. Statistical
      analysis was performed using the t-test. Results: In the 60 samples studied,
      differenceswere significant in smopkers vs. nonsmokers for micronuclei, (P=0.002)
      but not karyorrhexis or karyolysis. (P=0.789 andP=0.578, respectively). Also, the
      repair index demonstrated no statistically significant variation (P=0.107).
      Comparisonof the two subgroups of smokers demonstrated that the frequency of
      micronuclei in those with a history >10 years wassignificantly higher and the RI
      was significantly lower than with <=10 years (P=0.0001 and 0.04, respectively).
      Whilekaryorrhexis and karyolysis were also higher in the longer exposure
      individuals the differences were not significant(P=0.07 and 0.78, respectively).
      Conclusion: Among the nuclear changes investigated, micronuclei proved the
      morereliable indicator to assess the adverse effects of smoking on the oral
      mucosa, becoming prominent with increase insmoking history. In addition, while a
      "repair index" may have benefits for assessment of nuclear damage caused
      bysmoking, further research is necessary in this field.

PMID- 29172284
TI  - Inhibitory Effect of Aspirin on Cholangiocarcinoma Cells
AB  - Aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of cancer
      due to their anti-proliferative andapoptotic effects, which are the important
      mechanisms for their anti-tumor activity. Here, the effect of aspirin on
      humancholangiocarcinoma cells (KKU-214) and the underlying mechanisms of its
      action were explored. Cell proliferationwas measured by sulforhodamine B (SRB)
      assay, while cell cycle distribution and apoptosis were determined by
      flowcytometry. Western blotting was used to explore protein expression underlying
      molecular mechanisms of anti-cancertreatment of aspirin. Aspirin reduced cell
      proliferation in a dose- and time-dependent manner, and altered the cellcycle
      phase distribution of KKU-214 cells by increasing the proportion of cells in the
      G0/G1 phase and reducing theproportion in the S and G2/M phases. Consistent with
      its effect on the cell cycle, aspirin also reduced the expressionof cyclin D1 and
      cyclin-dependent kinase 4 (Cdk-4), which are important for G0/G1 cell cycle
      progression. Treatmentwith aspirin led to increased induction of apoptosis in a
      dose-dependent manner. Further analysis of the mechanismunderlying the effect of
      this drug showed that aspirin induced the expression of the tumor-suppressor
      protein p53 whileinhibiting the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2).
      Correspondingly, the activation of caspase-9 and -3was also increased. These
      findings suggest that aspirin causes cell cycle arrest and apoptosis, both of
      which couldcontribute to its anti-proliferative effect.

PMID- 29172285
TI  - Body Mass Index and Breast Cancer Risk among Thai Premenopausal Women: a Case
      Control Study
AB  - Background: Breast cancer (BC) is the leading malignancy in women with high
      incidence and mortality worldwide.Obesity is one of several established risk
      factors for chronic diseases including cancer. The objective of this researchwas
      to determine the association of body mass index (BMI) with BC among Thai
      premenopausal women (TPW).Materials and Methods: A case-control study was
      conducted among TPW attending the National Cancer Institute inBangkok, with 257
      cases and 257 controls in 2013-2014. Cases and controls were matched by age (+/-
      5 years), residentialarea and duration of attending. Data were collected with a
      questionnaire comprising 2 parts: part 1 socio-demographiccharacteristics, and
      part 2 health risk behavior and reproductive factors and BMI. The obtained data
      were analyzedusing descriptive and analytic statistics with a computerized
      statistical package. Results: The study participants weremainly 40-44 years old
      (60 %) with an average age of 39 years. The major type of BC was the invasive
      ductal carcinoma(91.8%). On univariate analysis, risk factors for BC among the
      TPW were family history of BC, history of benignbreast tumors, younger age at
      menarche, parity, miscarriage, contraceptive use, passive smoking, multivitamin
      use,and BMI (p<0.05). Multivariable conditional logistic regression analysis,
      controlling for possible confounding factors,revealed that a BMI 25-29.9 and >=
      30 kg/m2 increased the risk of BC by a factor of 2.09 and 2.37 times,
      respectively(OR=2.09, 95%CI =1.09-3.97; OR=2.37, 95%CI =1.24-10.06). Conclusions:
      A surveillance system of obesity shouldbe conducted in cooperation with
      information regarding physical activities and weight control among TPW as
      anessential measure to reduce BC risk.

PMID- 29172286
TI  - Epitope Mapping of Human HER2 Specific Mouse Monoclonal Antibodies Using
      Recombinant Extracellular Subdomains
AB  - Background: Human epidermal growth factor receptor 2 (HER2) is overexpressed in
      several human malignanciesand numerous studies have indicated that it plays
      important roles in the development and maintenance of the malignantphenotype.
      Targeting of HER2 molecules with monoclonal antibodies (mAbs) is a promising
      therapeutic approach.However, anti-HER2 mAbs affect cancer cells differently,
      depending on the distinct epitopes which are the targets.Methods: Reactivity of a
      panel of 8 mouse anti-HER2 mAbs was investigated by ELISA and Western blotting
      usingdifferent subdomains of the extracellular domain (ECD) of HER2. All
      subdomains, including I, II, III, IV, I+II,III+IV and full HER2-ECD were
      constructed and expressed in CHO cells. Cross-reactivity of the mAbs with
      othermembers of the human HER family and Cynomolgus HER2 was also studied by
      ELISA. The mAbs were also testedby immunohistochemistry (IHC) using HER2 positive
      breast cancer tissues. Results: Our results demonstrated that 3out of 8 mAbs
      detected conformational epitopes (1T0, 2A8 and 1B5), while 5 mAbs identified
      linear epitopes (1F2,1H9, 4C7, 1H6 and 2A9). Three of the mAbs recognized
      subdomain I, one reacted with subdomain I+II, 2 recognizedeither subdomain III or
      IV and 2 recognized subdomain III+IV. However, none of our mAbs recognized the
      subdomainII alone. The mAbs displayed either inhibitory or stimulatory effects on
      HER2-overexpressing tumor cells and did notreact with other members of the human
      HER family. The pattern of IHC results implied better reactivity of the
      mAbsrecognizing linear epitopes. Conclusions: Our findings suggest that paired
      subdomains of HER2 are essential formapping of mAbs recognizing conformational
      epitopes. Moreover, there seems to be no association between subdomainspecificity
      and antitumor activity of our anti-HER2 mAbs.

PMID- 29172287
TI  - Polycystic Ovarian Morphology may be a Positive Prognostic Factor in Patients
      with Endometrial Cancer who Achieved Complete Remission after Fertility-Sparing
      Therapy with Progestin
AB  - Background: The most studied fertility-sparing therapy for endometrial cancer
      (EC) is oral progestin therapy.However, complete remission (CR) rate after
      progestin therapy is not enough ranging from 60 to 80 %, with highrecurrence
      rate. Clinical features that predict treatment efficacy and recurrence after
      progestin therapy have not yetbeen revealed in detail. The aim of this study was
      to investigate prognostic factors in patients with EC who achievedCR after
      medroxyprogesterone acetate (MPA) therapy. Methods: We retrospectively reviewed
      35 EC patients treatedwith MPA at our institution between 2000 and 2016.
      Following confirmation of endometrioid adenocarcinoma G1,patients orally took 600
      mg MPA daily for 26 weeks. Patients with CR periodically took oral
      contraceptives. Theassociation of recurrence-free survival (RFS) with several
      clinical features including age, body mass index (BMI),and polycystic ovarian
      morphology (PCOM) was analyzed. Results: Of 35 patients, 25 (71%) achieved CR,
      whereas10 (29%) underwent hysterectomy due to failure of MPA therapy. Eleven
      (44%) of 25 patients with CR successfullygave birth after MPA therapy, whereas 8
      (32%) developed recurrence. On univariate analysis, PCOM was
      significantlyassociated with better recurrence-free survival (RFS) (P=0.009), and
      BMI >=25 kg/m2 exhibited a nonsignificant trend forlonger RFS (P=0.0674).
      Although multivariate analysis failed to detect any valid hazard ratio (HR),
      absence of PCOMand non-obesity were both independent risk factors for recurrence
      (P=0.00293 and P=0.0201, respectively). Notably,none of 10 cases with PCOM
      experienced recurrence under maintenance with oral contraceptives. Conclusion:
      PCOMmight be a good prognostic factor in those achieving CR after MPA therapy for
      EC.

PMID- 29172288
TI  - Prevalence of Abnormal Pap Smears: A Descriptive Study from a Cancer Center in a
      Low-Prevalence Community
AB  - Background and aims: Cervical cancer is the fourth most common cancer in women
      worldwide and the 13th inJordan. The cervical smear (Pap smear) is a simple
      approach to detect pre-cancerous cervical lesions. The aim of thisstudy was to
      evaluate the prevalence of abnormal cervical smears in women seen at the Early
      Detection/CommunityOutreach clinic of King Hussein Cancer Center (KHCC).
      Materials and Methods: In this retrospective study, reportsof routine cervical
      Pap smears performed in the pathology department at KHCC from January 2007 to
      December2016, were reviewed. During this period, a total of 5,529 routine smears
      were assessed for epithelial abnormalities andhistopathological grading. Results:
      A total of 210 (3.8%) abnormal Pap smears were found, with atypical squamouscell
      of undetermined significance (ASC-US) reported in 110 (52.4%) cases, atypical
      glandular cells of underminedsignificance (AGUS) in 58 (27.6%), low grade
      squamous intra-epithelial lesion (LSIL) in 27 (12.9%) and high gradeintra
      epithelial lesion (HSIL) in 13 (6.2%). Only single cases of ASC-H and squamous
      cell carcinoma were reported.The available biopsies showed benign findings in
      70.1% of cases, low grade squamous intraepithelial lesions in 11.5%and high grade
      squamous intraepithelial lesions in 18.4%. Conclusions: The low epithelial cell
      abnormality (EPCA)prevalence illustrated in this study argues against
      introduction of population-based HPV testing and vaccination. Itcalls for a more
      cost-effective measures in a country with limited resources, where a more widely
      available Pap-smeartesting might suffice.

PMID- 29172289
TI  - Prevalence of Helicobacter Pylori Infection in Dyspeptic Patients in Andkhoy
      Afghanistan
AB  - Background: The prevalence of Helicobacter pylori (H. pylori) infection is
      reported to be more than 50% worldwide.It has been associated with peptic ulcer
      disease, gastric carcinoma, and mucosal-associated lymphoid tissue lymphoma.The
      seroprevalence of H. pylori varies greatly among societies and geographical
      locations. The objective of thisstudy was to determine the seroprevalence and
      factors associated with H. pylori infection among dyspeptic patientsin
      Afghanistan. Materials and Methods: This cross-sectional study was designed to
      determine the seroprevalence ofH. pylori among dyspeptic patients in an
      outpatient clinic in Andkhoy, Afghanistan from January 2017 to April 2017.Data
      were obtained from patients using a questionnaire, including socio-demographic
      data and history of smokingand dyspeptic symptoms. Serum samples were also
      collected from the patients and tested for H. pylori antibodiesusing the enzyme
      linked immunosorbent assay. Results: A total of 152 patients with dyspepsia were
      included in theanalysis; 59 were men (40.0%), and 93 were women (60.0%). The
      overall seroprevalence of H. pylori was 75.6%. Thepredictor of seroprevalence of
      H. pylori was found to be illiteracy (odds ratio [OR] 4.99, 95% confidence
      interval [CI]1.03!24.17), epigastric pain (OR 12.01, 95% CI 3.56- 40.52), and
      rural population (OR 9.66, 95% CI 3.36- 27.82).There was an inverse association
      between employed status and seroprevalence of H. pylori (OR 0.08, 95% CI 0.01
      0.52). Conclusions: The seroprevalence of H. pylori was high among patient with
      dyspepsia in an outpatient clinicin Afghanistan. Illiteracy, unemployment and
      rural populations, and epigastric pain were significantly associated withH.
      pylori infection.

PMID- 29172290
TI  - Multi-Gene Expression in Anthracosis of the Lungs as One of the Risk Factors for
      Non-Small Cell Lung Cancer
AB  - Background: Anthracosis of the lung occurs due to the deposition of carbon and
      silica in the mucosa and submucosa,manifested as black lesions. The association
      of anthracosis with lung cancer has remained to be clearly elucidatedThe current
      study aimed to assess the P16, CDH1 and LUNX genes expression level to evaluate
      the association ofanthracotic lesions in the lungs with the occurrence of non
      small cell lung cancer. Methods: Forty biopsy sampleswere taken from the center
      and 40 from the margins of black anthracotic lesions in the lungs; RNA was
      extracted fromthe samples and cDNA was synthesized. Real-time reverse
      transcription polymerase chain reaction (RT-PCR) wasperformed to assess the
      expression of P16, CDH1 and LUNX genes. All steps were performed in triplicate.
      Results: Asignificant reduction in P16 gene expression was noted at the center
      compared to the margins of the lesions (P<0.001).expression level of CDH1 at the
      center of lesions was significantly lower than margins (P<0.001). However,
      LUNXgene had significantly higher expressionlevel at the center compared to
      margins (P<0.001). Conclusion: Decreasedexpression of P16 and CDH1 and increased
      expression of LUNX tumor genes were noted at the center of anthracoticlesions.
      Significant increase in expression of LUNX gene in NSCLC indicates an association
      between anthracosis andNSCLC, according to which, anthracotic patients may carry
      a high risk for NSCLC.

PMID- 29172291
TI  - The Utilization of Karyotyping, iFISH, and MLPA for the Detection of Recurrence
      Genetic Aberrations in Multiple Myeloma
AB  - Multiple myeloma (MM) is a hematological malignancy characterized by abnormal
      accumulation of clonal plasmacells in the bone marrow. Recently, multiplex
      ligation-dependent probe amplification (MLPA) has emerged as an effectiveand
      robust method for detection of common genetic alterations in MM patients. Here,
      we aimed to confirm MLPAutility for this purpose and furthermore to test the
      feasibility of a combination of karyotyping, interphase fluorescencein situ
      hybridization (iFISH) and MLPA methods for diagnosis, prognostic assessment and
      risk stratification of MM.Thirty-five genomic DNA samples isolated from CD138
      enriched plasma cells from bone marrow of MM patients wereanalyzed using the MLPA
      method. We found that amp (1q) was the most frequent genetic alteration (48.6%)
      in the testedsamples, followed by del (1p) and del (13q) (34.3%). Moreover,
      concordant results between sensitivity and specificityof iFISH and MLPA for the
      detection of del (13q) (p-value >0.05) and del (17p) (p-value >0.05) were
      obtained. Insummary, we could provide evidence of MLPA assay utility for the
      detection of common genetic alterations in MM.The combination of karyotyping,
      iFISH, and MLPA proved very helpful for clinical risk stratification.

PMID- 29172292
TI  - Detection of Juxtapleural Nodules in Lung Cancer Cases Using an Optimal Critical
      Point Selection Algorithm
AB  - Detection of lung cancer through image processing is an important tool for
      diagnosis. In recent years, image processingtechniques have become more widely
      used. Lung segmentation is an essential pre-processing step for most
      (CAD)schemes. An automated system is proposed in this paper for identifying lung
      cancer from the analysis of computedtomography images by performing nodule
      segmentation using an optimal critical point selection algorithm (OCPS)which
      improves the detection of shape- and size-based juxtapleural nodules located at
      the lung boundary. A suspect areaof nodule is obtained with the help of a
      bidirectional chain code (BDC) approach and the OCPS This algorithm is usedto
      reduce the time consumption to detect the lung nodule and thereby reduce the
      computational complexity. Shape andsize features are extracted for the area
      between two critical points to facilitate classification as nodule or non
      nodulewith the help of a support vector machine and random forest classifiers.
      This automated method was tested on computedtomography (CT) studies from the lung
      imaging database consortium (LIDC). The results are compared with theexisting
      techniques using various performance measures such as precision rate, recall
      rate, accuracy and F-measure.The obtained experimental results indicate that the
      OCPS combined with a random forest classifier performs better interms of
      performance evaluation metrics than existing approaches, with less requirement
      for computation.

PMID- 29172293
TI  - Oncologists' Perspectives on Consolidation Radiation Treatment after Chemotherapy
      for Lymphomas: A Survey Study by the Lymphoma Working Committee of the Turkish
      Oncology Group (TOG)
AB  - In this study, we aimed to determine the perspectives of medical and radiation
      oncologists regarding consolidationradiotherapy in patients with a complete
      response after chemotherapy for Hodgkin's and non-Hodgkin's lymphomas.The survey
      was designed to identify demographic and occupational features of medical and
      radiation oncologists andtheir views on application of consolidation radiotherapy
      in their clinical practices, as based on a five-point Likert scale(never, rarely,
      sometimes, often, and always). The study covered 263, out of 935, physicians
      working in the oncologyfield as either medical or radiation oncologists; the rate
      of return on the invitations to participate was 28%. The majorityof the
      participants were male radiation oncologists, with a duration of between 5 and 10
      years of work as a universityhospital official, and the mean age was 38 +/- 14
      (years). Although the most commonly followed international guidelineswere NCCN,
      among the physicians, the majority of the respondents suggested that the
      guidelines were unclearregarding recommendations for consolidative radiotherapy.
      The administered dose for consolidative radiotherapy inlymphoma patients was
      indicated as 40 Gy by 49% of all the physicians and the most common cause of
      hesitancyconcerning consolidative radiation treatment was the risk of secondary
      malignancies as a long-term adverse effect(54%). In conclusion, we suggest that
      medical oncologists could be most active in the treatment of lymphoma througha
      continuous training program about lymphomas and current national guidelines.

PMID- 29172294
TI  - Association of Voltage-Gated Sodium Channel Genetic Polymorphisms with
      Oxaliplatin-Induced Chronic Peripheral Neuropathy in South Indian Cancer Patients
AB  - Oxaliplatin is a platinum drug active against digestive tract cancers. Among its
      side effects, peripheral neuropathyis one of the dose-limiting toxicities. This
      affects around 50 to 70% of patients but the pathophysiology of developmentof
      oxaliplatin-induced peripheral neuropathy (OXAIPN) remains unclear. Sodium
      channels (SCNAs) play major role inneuronal electrical signaling processes and
      mutations in SCNAs lead to various neuronal diseases involving the centraland
      peripheral nervous systems. In this study, we evaluated whether SCNA genetic
      variants might be associated withrisk of chronic OXAIPN in patients with
      digestive tract cancers treated with oxaliplatin. Methodology: Blood samplesfrom
      228 digestive tract cancer patients who had received oxaliplatin in adjuvant and
      neoadjuvant or metastatic settingswere obtained and genomic DNA was extracted by
      phenol-chloroform extraction. Genotyping was performed withthe real-time
      polymerase chain reaction (RT-PCR) using validated real-time TaqMan single
      nucleotide polymorphism(SNP) genotyping assays. Neuropathy was evaluated and
      graded according to National Cancer Institute CommonToxicity Criteria (NCI-CTC)
      version 4.03. Results: We found that the rs6746030 polymorphic variant of SCN9A
      wassignificantly associated with a higher incidence of chronic OXAIPN (GA+AA vs
      GG: OR=1.8, 95% CI=1.04-3.4, P=0.04;dominant model) while the rs6754031 variant
      was linked with a lower incidence (OR=0.45, 95% CI=0.22-0.77, P=0.005;dominant
      model). The SCN 10A polymorphic variant was associated with severity of chronic
      OXAIPN (P=0.006,OR=2.0, 95% CI=1.2 - 3.3). Conclusion: The results of the present
      prospective study provide evidence in support ofa causal relationship between
      chronic OXAIPN and voltage gated sodium channel polymorphisms. However,
      furtherstudies from independent groups are required to validate these results.

PMID- 29172295
TI  - Evaluation of Mir-224, Mir-215 and Mir-143 as Serum Biomarkers for HCV Associated
      Hepatocellular Carcinoma
AB  - HCV induced hepatitis and hepatocellular carcinoma as its sequel are major health
      problems world-wide and especiallyin Egypt. For diagnosis and during treatment of
      liver diseases, liver functions are monitored through determinationof serum
      levels of liver enzymes and alpha-fetoprotein although the obtained information
      is generally not sufficient foreither early detection of hepatic insult or
      effective follow up of therapeutic effects. More sensitive biomarkers mayhelp to
      achieve these goals. MiRNAs are small non-coding RNAs that have an important role
      in gene expression andregulation. Many, such as miR-224, miR-215, miR-143 are
      correlated with tumor appearance and with the degree offibrosis in lung, breast
      and colon cancer. This study was performed to estimate the level of these miRNAs
      in serum ofpatients with HCV-associated hepatitis and HCC in relation to grade of
      hepatitis, stage of fibrosis and differentiation oftumor tissue. In addition,
      correlations between serological and tissue levels were assessed. A total of 80
      patients wereexamined, out of which 50 were included in the study. Blood samples
      and tissue specimens from malignant tumor andcorresponding non-tumor tissue of
      HCV hepatitis patients were collected. Blood samples from 20 healthy
      volunteerswere also obtained as controls. It was found that miRNAs profiles
      differed in HCC patients compared to controls andHCV-associated hepatitis cases.
      Distinction of tumor grade and fibrosis stage of patients as well as between
      differentgrades of tumor differentiation proved possible, making miRNAs promising
      biomarkers for diagnosis and assessmentof treatment response of HCC patients.

PMID- 29172296
TI  - Significance of the Cytological Signs of Human Papillomavirus Infection in Anal
      Pap Smears of Human Immunodeficiency Virus-Infected Japanese Men Who Have Sex
      with Men
AB  - Purpose: The incidence of invasive anal cancer (IAC) has been increasing among
      human immunodeficiencyvirus (HIV)-positive men who have sex with men (MSM).
      Although cytological diagnosis is the modality of choicefor screening cases of
      IAC, it is associated with lower sensitivity and specificity. Therefore, the
      present study aimedto evaluate new cytological signs of human papillomavirus
      (HPV) infection that may contribute to improving analcytology. Methods: Anal
      cytology and HPV testing were performed using SurePath liquid-based cytology on
      samplesobtained from 37 HIV-positive Japanese MSM. Subsequently, a histological
      biopsy based on high-resolution anoscopywas performed in MSM with abnormal
      cytological findings indicative of atypical squamous cells of
      undeterminedsignificance (ASC-US) +. Also, anal Papanicolaou (Pap) smears were
      performed to determine cellularity, presenceof dysplastic squamous cells, and
      other cytological signs of HPV infection. Results: Of the 37 MSM who
      underwentanal cytology, six tested negative for intraepithelial lesion or
      malignancy, three cases exhibited ASC-US, 17 exhibitedlow-grade squamous
      intraepithelial lesion (LSIL), nine exhibited high-grade squamous intraepithelial
      lesion (HSIL),and two remained undiagnosed. The anal Pap smears of 28 (96.6%) of
      the 29 MSM with abnormal cytological findingsof ASC-US+ exhibited anal
      intraepithelial neoplasia (AIN), as revealed by histological biopsy. The median
      value(minimum-maximum) of the cellularity of anal Pap smears was 12 (0-70.5)
      nsc/hpf. In 26 MSM with LSIL and HSIL,the median dysplastic squamous cells count
      was 14 (2-152) dsc/smear and the cytological sign of HPV infectionwas 11 (2-71)
      hpv/smear. Of all anal Pap smears that revealed ASC-US+, 96.6% exhibited
      cytological signs of HPVinfection. Compression-positive binucleated cells were
      the most prevalent among all cytological signs of HPV infection.Conclusion: For
      anal cytology, instead of considering a small number of dysplastic squamous
      cells, screening basedon cytological signs of HPV infection may be beneficial for
      improving the diagnosis of AIN.

PMID- 29172297
TI  - Impact of Smoking on Health-Related Quality of Life: A General Population Survey
      in West Iran
AB  - This study was aimed at assessing any association between smoking and health
      related quality of life (HRQoL)among adults aged 18 years and above living in
      Kermanshah city, western Iran. A cross-sectional study was conducted ona total
      sample of 1,543 participants obtained by convenient sampling during the period
      from February 1st to May 30th,2017. Data were collected using a self
      administrated questionnaire. The HRQoL of the study participants was assessedwith
      reference to the EuroQol 5-dimensions-3-level (EQ-5D-3L). The impact of smoking
      behavior of the participantson HRQoL with controls for potential confounders was
      examined by multiple regression. Out of the total of 1,543participants, current
      smokers, past smokers, and never smokers accounted for 19.7%, 4.2% and 76.1%,
      respectively. Themean EQ-5D indices were 0.69 +/-SD 0.20, 0.70 +/- SD 0.22, and
      0.78 +/- SD 0.16. The highest proportion of self-reportedproblems (including both
      'some' and 'severe') were related to current, heavy smokers, with high nicotine
      dependence.Regression analysis indicated that current smokers had a significantly
      lower HRQoL compared to past smokers andnever smokers (p < 0.05). The heavy
      smokers also had a significantly lower HRQoL score than moderate and lightsmokers
      (p < 0.05) and there was an inverse relationship between the HRQoL score and
      nicotine dependence (p<0.05).The current smokers, heavy smokers, and high
      nicotine dependent smokers had lower HRQoL scores. These findingsprovide inputs
      for better understanding and for devising interventions for smoking cessation,
      reducing the number ofcigarettes smoked per day and nicotine dependency.

PMID- 29172298
TI  - Right Heart Thrombus in Transit: Unusual Echocardiographic Finding in a patient
      with Acute Pulmonary Embolism.
AB  - Eighty year old male patient with heart failure preserved ejection fraction
      (EF),Obstructive sleep apnea, peripherovascular disease admitted with
      increasingshortness of breath and found with pulmonary emboli. Baseline 2D
      echocardiogramperformed demonstrated preserved ejection fraction and a
      rightthrombus in transit. Anticoagulation with weight based-low molecularweight
      heparin was given for six days. Follow-up echo performed demonstratedcomplete
      dissolution of right heart thrombi. Since there was complete dissolutionof
      thrombi seen on right atrium, anticoagulation with Rivaroxaban was given instead.

PMID- 29172299
TI  - The effect of anti-IgE therapy in knee osteoarthritis: a pilot observational
      study.
AB  - Osteoarthritis is a whole-joint disease and its pathogenesis remains poorly
      understood. Recent evidence proposed the importance of the innate immune system
      as trigger of synovium inflammation following the degeneration of cartilage.
      Moreover, synovial mast cells (MCs) might be correlated with pain and disability
      reported by patients. Anti IgE therapy represents a new class of MCs stabilizing
      agent, licensed for people with asthma and chronic urticaria. Therefore, we
      studied if the stabilizing effect of anti IgE would improve the pain and
      disability in patients affected by knee osteoarthritis and atopic disease. This
      pilot study provides the first evidence that anti IgE treatment induces a short
      term clinical improvement supporting the role of MCs in osteoarthritis.

PMID- 29172300
TI  - Clinical and radiographic short mid-term outcomes of primary total stabilizer
      knee arthroplasty.
AB  - A successful Total Knee Arthroplasty (TKA) requires stability, but rarely in
      primary TKA, a prosthesis with more constraint than a posterior-stabilizer (PS)
      is necessary. In patients with severe varus/valgus deformities with incompetent
      collateral ligaments or in knees that cannot be adequately balanced after
      ligaments release, a total-stabilizer (TS) prosthesis may be required. The
      purpose of our retrospective study is to evaluate clinical and radiographic
      outcomes at short mid-term follow-up in patients treated with a TS TKA. Between
      January 2013 and August 2016, 36 patients (38 knees) were treated with Stryker
      Triathlon TS cemented implants. Clinical and radiographic evaluation were
      performed preoperatively and postoperatively at 1 month, 3 months, 6 months, 1
      year and at 1-year intervals thereafter. At final follow-up, 33 patients (35
      knees) remained and were included in this study and followed with a mean follow
      up of 26.6 months. Clinical evaluation was performed using the Western Ontario
      and McMaster Universities Arthritis Index (WOMAC score) and the Knee Society
      rating system that is subdivided into a knee score (KS) that rates only the knee
      joint itself and a functional score (FS). Knee Score (KS) and Functional Score
      (FS) increased significantly from a mean pre-operative value of 48 and 45,
      respectively, to a post-operative value at last follow-up of 86 and 82,
      respectively. Also WOMAC score improved significantly: the mean pre-operative
      WOMAC score was 45, while the mean post-operative WOMAC score, at last follow-up,
      was 19. The difference between pre- and post- operative results was significant
      at statistical analysis. In our opinion, when the adequately prosthesis balancing
      isn't possible, because of primary or secondary severe varus/valgus deformity or
      severe soft tissues retraction, an available option is to perform a total knee
      arthroplasty with a total stabilizer polyethylene insert. TS prosthesis gives
      more stability during the most of ROM and, in addition, Triathlon system provides
      surgeons the possibility to choose a more constrained implant, than a standard PS
      one, during surgical procedure saving the bone stock. Our experience with this
      kind of prosthesis has provided good clinical and radiographic outcomes at a
      short mid-term follow-up with a low-rate of complications.

PMID- 29172301
TI  - Modifying Our MCI Practices.

PMID- 29172302
TI  - MCI Transports. EMS liability for non-EMS patient transports.

PMID- 29172303
TI  - Out on a Limb. Establish clear protocols for field amputations.

PMID- 29172304
TI  - Face Saver. Better options for cooling.

PMID- 29172305
TI  - Agent of Change. Prepare your trainee by being an example.

PMID- 29172306
TI  - What is Restorative Dentistry?

PMID- 29172307
TI  - The Paradoxes of Phantom Bite Syndrome or Occlusal Dysaesthesia ('Dysesthesia').
AB  - Phantom bite syndrome was first described by Marbach over 40 years ago as a mono
      symptomatic hypochondriacal psychosis. He used the term to describe a prolonged
      syndrome in which patients report that their 'bite is wrong' or that 'their
      dental occlusion is abnormal' with this causing them great difficulties. This
      strong belief about 'their bite' being the source of their problems leads to them
      demanding, and subsequently getting, various types of dentistry carried out by
      multiple dentists and 'specialists'. Sadly, even after exhaustive, painstaking,
      careful treatment, none of the dental treatments manages to solve their perceived
      'bite problems'. This is because they suffer from a psychiatric illness involving
      a delusion into which they continue to lack insight, in spite of the failures of
      often sophisticated dental treatments.1,2,3 In summary, dental practitioners, or
      other specialists, who suspect that they might be dealing with such a problem
      should refer these patients early on for specialist management by an appropriate
      specialist within the secondary care settings, preferably before they get trapped
      into the time-consuming quagmire of their management. A 'Phantom Bite
      Questionnaire', which is available to download free, might help. Clinical
      relevance: This article aims to provide professionals in various fields with
      guidelines on detecting, diagnosing and managing patients with Phantom Bite
      Syndrome (PBS). This is desirable in order to prevent extensive, or unnecessarily
      destructive, or unstable dental treatment being undertaken on such patients in a
      vain attempt to solve their problems with 'dentistry' when, in fact, these are
      really due to underlying mental health issues.

PMID- 29172308
TI  - A New Perspective on Dentine Hypersensitivity - Guidelines for General Dental
      Practice.
AB  - The aim of this review is to update dental professionals on the issues and
      challenges associated with the clinical management of dentine hypersensitivity
      (DH) and to provide simple guidelines based on presenting clinical features that
      may help them successfully manage the condition in their day-to-day clinical
      practice. Details on the management of DH have been previously published in
      Dental Update which indicated that there was a need for such guidelines. The
      authors of these guidelines also suggested that, despite the various published
      clinical studies, there does not currently appear to be one ideal desensitizing
      agent that can be recommended for treating DH. A joint working relationship
      between the dental professional and the patient in changing the patient's
      behaviour is therefore essential if the condition is to be successfully treated. 
      Clinical relevance: Dentine hypersensitivity is a persistent and a troublesome
      clinical condition which at times is under diagnosed by dental professionals who
      may struggle to resolve the problem to their patients' satisfaction successfully.
      The recent UK Forum guidelines on the management of DH, based on the presenting
      features of the condition, provide practical recommendations, helping dental
      professionals to manage this persistent problem correctly.

PMID- 29172309
TI  - Pit Crew Proof. Study shows CPR method has better survival rates.

PMID- 29172310
TI  - Could Video Glasses Contribute to Behaviour Management in the 21st Century?
AB  - Dental fear in the paediatric population can be a significant barrier to
      providing optimal dental care. Pharmacological management techniques utilized to
      manage anxiety, such as conscious sedation and general anaesthesia, are expensive
      and require specialized equipment with additional staff training. With recent
      advances in technology, video glasses are an economic and novel distraction
      technique that may aid in improving behaviour management and facilitate dental
      treatment.  Clinical relevance: Nervous children may find difficulty in accessing
      care owing to their inability to co-operate and accept dental treatment. This
      paper describes an innovative technique that may aid the clinician in overcoming
      this barrier.

PMID- 29172311
TI  - Case Report: Metastatic Infratemporal Soft Tissue Myeloma Presenting as a Numb
      Lower Lip.
AB  - This is a case of a patient presenting to his general dental practitioner (GDP)
      with altered sensation in his lower lip with no obvious cause. Due to a prompt
      referral, the patient was investigated and diagnosed with an extramedullary
      presentation of multiple myeloma. A numb lip can present in general dental
      practice, although this is not common. There are several causes, for example,
      dental infection or fractured mandible. Clinical relevance: It is very important
      for the dental practitioner to recognize when there could be a potential sinister
      underlying cause and prompt referral, under the two week rule referral system, is
      indicated

PMID- 29172312
TI  - City on Alert. Lessons learned from the San Bernardino terrorist attack.

PMID- 29172313
TI  - Frequently Asked Questions about Vital Tooth Whitening.
AB  - Improving patients' aesthetics is an important request in daily practice. Tooth
      whitening is a treatment option available for improving aesthetics. This paper
      will pose questions asked by our patients on bleaching techniques and outcomes
      and offer appropriate up-to-date answers.  Clinical relevance: This paper
      addresses the most important questions raised by patients and colleagues
      concerning vital tooth whitening (VTW).

PMID- 29172314
TI  - The Limitations of Short-Term Orthodontics and Why We Still Need Specialists - A
      Review of the Current Literature.
AB  - Short-term orthodontics (STO) serves to align anterior teeth. It has become
      popular in cosmetic dentistry as an alternative to destructive veneers and
      lengthy conventional orthodontics. The aim of this article is to raise awareness
      of the clinical limitations of STO and highlight some of the difficulties
      encountered with orthodontic retention. It also gives an overview of accredited
      training available to dentists who wish to develop their orthodontic skills. 
      Clinical relevance: Greater awareness of the clinical limitations of short-term
      orthodontics will aid GDPs in appropriately selecting their cases and obtaining
      informed consent from patients. In addition, the article serves as encouragement
      for those GDPs wishing to develop their orthodontic skills and pursue further
      accredited training.

PMID- 29172315
TI  - Sore or Swollen Lips Part 3: Diagnosis and Treatment.
AB  - This series of three papers reviews the causes, diagnosis and differential
      diagnosis, and outlines the management of sore and/or swollen lips. Clinical
      relevance: Sore and/or swollen lips are not uncommon, often have a local cause
      but may reflect a systemic disease. The previous 2 papers in the series discussed
      their causes. This paper reviews their diagnosis and treatment.

PMID- 29172316
TI  - Serving the Customer - Do Patient Feedback and Questionnaires Improve Quality?
AB  - This review article aims to analyse whether patient feedback and questionnaires
      improve quality of care. It is recognized that patients cannot assess the medical
      competence of the clinician, yet patient experience provides an insight into the
      process of care through the patients' eyes. Patient experience measures are more
      reliable for use to assess quality than patient satisfaction surveys. It is
      inappropriate to use patient satisfaction surveys as a basis for remuneration of
      dentists within the NHS. Patient Reported Outcome Measures (PROMs) have been a
      successful measure of patient experience in medicine and their introduction to
      dentistry needs to be considered.  Clinical relevance: This article will enable
      clinicians to understand the importance of patient experience measures as a more
      reliable way of improving the quality of clinical care than patient satisfaction
      surveys.

PMID- 29172317
TI  - Clinical Challenges Q&A 27. Soreness in the Floor of the Mouth.

PMID- 29172318
TI  - Technique Tips:  A New Look at Repairing Fractured Metal-Ceramic Restorations:
      Use of a Universal Bonding System and Resin Composite, following Sandblasting.

PMID- 29172319
TI  - Bystander Response. Leveraging bystanders as medical force multipliers in high
      threat incidents.

PMID- 29172320
TI  - Fake CPD.

PMID- 29172321
TI  - Type-1 Dentine Dysplasia - Diagnostic and Clinical Challenges in Restorative
      Management.
AB  - Type-1 dentine dysplasia is a rare hereditary condition, associated with an
      abnormality in dentine formation. Deceptively, teeth have the clinical appearance
      of normality, however, radiographically, a different picture is seen; with
      multiple periapical radiolucencies associated with non-carious, unrestored teeth.
      This article reports the diagnostic and management challenges associated with
      dentine dysplasia in adults.  Clinical relevance: Early diagnosis and preventive
      advice within primary care are imperative in the long-term outcomes.

PMID- 29172322
TI  - The Value of Cone Beam Computed Tomography in the Management of Dentigerous Cysts
      - A Review and Case Report.
AB  - Cone Beam Computed Tomography (CBCT) has recently seen an expansion in use,
      however there are few robust, evidence-based guidelines to inform practitioners.
      This article reports the case of a large dentigerous cyst in the maxilla
      affecting the eruption of multiple teeth, considers the use of CBCT in the
      management of such lesions, and discusses guidelines on the use of CBCT in
      dentistry.  Clinical relevance: As CBCT use increases it is important that
      practitioners understand the guidelines surrounding its use. Due to the
      prevalence of dentigerous cysts, it is likely that they will be encountered
      clinically, and it is important that clinicians referring patients with such
      lesions are familiar with the principles of managing them.

PMID- 29172323
TI  - A Predictable Alternative to a Smile in Six Months?
AB  - The aim of this article is to explore the use of IncognitoTM Lite as an
      alternative to competitors advertising a 'Smile in Six Months' or rather short
      term orthodontics for improving dental appearance through tooth movement. The
      focus is on the varied clinical use of this appliance system and its comparative
      advantages, disadvantages and placement techniques. Some alternatives are
      discussed and appraised. Two cases successfully treated with IncognitoTM Lite are
      then presented.  Clinical relevance: A reliable and predictable tool for
      aesthetic alignment of teeth, creating a broader range of treatment options for
      both the clinician and the patient.

PMID- 29172325
TI  - Periodontal Treatment in Patients with Learning Disabilities Part 2: Professional
      Mechanical Intervention.
AB  - The first part of this two part series discussed the potential barriers and risk
      factors that may lead to an increased incidence and severity of periodontal
      disease amongst patients with learning disabilities. Additionally, preventive
      strategies and tools that can be used by general dental practitioners, oral
      health promotion teams as well as specialists within the field to control and
      prevent disease progression were explored. To prevent periodontal disease
      progression and attain optimal periodontal health, a combination of prevention
      and professional mechanical instrumentation is usually required. The second part
      of the series concentrates on the role of the dental professional in implementing
      professional mechanical instrumentation to attempt to reduce the burden of
      disease further in this patient group.  Clinical relevance: Although research
      continues into which professional techniques for instrumentation are the most
      successful amongst patients with periodontal disease, very little data
      specifically explore the needs of patients with learning disabilities, despite
      their high unmet needs. This paper aims to report on any available data present
      to produce suggestions for care.

PMID- 29172326
TI  - Efficient Mass Transport. Setup, operation and management of the transportation
      group at an MCI.

PMID- 29172327
TI  - Head and Neck Cancer Patients - Information for the General Dental Practitioner.
AB  - Salivary gland damage is the most common adverse effect associated with radiation
      therapy to the head and neck. A combination of hyposalivation and dietary
      changes, with a reduced emphasis on oral hygiene practices can contribute to a
      massive increase in a person's caries risk status. This can be further
      complicated by limited mouth opening. To enable optimal dental care for head and
      neck cancer patients before, during and after radiation therapy, patients must be
      informed and educated about the potential risks of dental caries and the
      preventive strategies available. All patients should receive a pre-radiotherapy
      dental assessment by a Restorative Dentistry Consultant. This information will be
      delivered to the patient, often at an emotionally charged time, and can be lost
      amongst all the information related to other aspects of his/her cancer
      management. General Dental Practitioners (GDPs) are therefore in a pivotal
      position to reiterate this information post radiation therapy and ensure
      compliance with preventive strategies, with the overall aim to improve quality of
      life and avoid the need for future extractions and the resulting risk of
      osteoradionecrosis.  Clinical relevance: This article highlights the GDP's role
      in the shared management of head and neck cancer patients who have received
      radiotherapy as part of their cancer treatment. The critical issue of dental
      caries, one of the late effects of radiation-induced hyposalivation, will be
      focused upon. Other side-effects, such as trismus and osteoradionecrosis, will
      also be discussed. This article aims to supply GDPs with accurate information to
      provide to their patients with post radiation therapy, whilst highlighting what
      treatment is within their remit and when it may be appropriate to refer.

PMID- 29172329
TI  - Treatment Planning for Mandibular Third Molars.
AB  - NICE guidance for mandibular third molars has been available since 2000. This was
      set up to limit the surgical treatment of these teeth to symptomatic patients.
      There are numerous risks involved with surgical treatment of mandibular third
      molars and these should be explained in detail to the patient. Common and serious
      complications of mandibular third molar surgery are damage to the inferior
      alveolar and lingual nerve. Predicting the risk of inferior alveolar nerve injury
      is useful for treatment planning. The orthopantomogram (OPT) is the baseline
      special test for assessing this and numerous signs on an OPT can predict an
      increased risk of injury to the nerve. Cone beam computed tomography (CBCT) is
      being more frequently used to assess this relationship further and can influence
      treatment planning. Coronectomy is a technique whereby the crown of the tooth is
      sectioned and removed leaving the roots in situ. This has proven to be a useful
      technique in high risk cases, but is not without its own complications. The
      increase in availability of CBCT imaging and the recent resurgence of coronectomy
      as a treatment modality can increase the number of treatment options available to
      patients. We have proposed an algorithm to aid the treatment planning and
      informed consent processes associated with mandibular third molar surgery. 
      Clinical relevance: This article is relevant to primary and secondary care dental
      practitioners as it will aid the investigation, treatment planning, correct
      referral and management of patients with problematic mandibular third molars.

PMID- 29172328
TI  - Surgical Emphysema: A Rare Complication of a Simple Surgical Dental Extraction
      Without the Use of an Air-Driven Rotor.
AB  - Surgical emphysema is a rare complication of dental extractions, often associated
      with the use of high-speed air rotors. This report describes a case of extensive
      surgical emphysema following a simple surgical extraction of a LL6 under local
      anaesthetic. There was no use of air-driven handpieces during the procedure. The
      patient developed extensive surgical emphysema bi-laterally in both cervical neck
      and facial planes. After prophylactic antibiotics with careful monitoring in a
      secondary care setting, the patient made a full unremarkable recovery.  Clinical
      relevance: Simple extraction of teeth is a procedure carried out daily by most
      general dental practitioners. However, the risk of surgical emphysema without the
      use of high-speed air rotors or instruments using pressurized air/water is not
      well known or documented.

PMID- 29172330
TI  - Waterlogged. San Diego Fire-Rescue lifeguards faced with MCI in the water.

PMID- 29172331
TI  - The Use of All-Ceramic Resin-Bonded Bridges in the Anterior Aesthetic Zone.
AB  - For several years, all-ceramic resin-bonded bridges (RBBs) have been considered
      an aesthetic treatment option for the replacement of missing teeth in the
      anterior region. With continued developments in technology, various different
      ceramic materials have been used to fabricate all-ceramic RBBs including
      zirconia, glass-reinforced, alumina-based ceramics, and lithium disilicate glass
      ceramics. The aim of this article is to provide an overview of all-ceramic RBBs,
      the advantages and disadvantages associated with these prostheses, as well as to
      demonstrate their application in replacing missing anterior teeth.  Clinical
      relevance: To present the current literature and clinical application of all
      ceramic resin-bonded bridges for replacing missing anterior teeth.

PMID- 29172332
TI  - Delivering Death Notifications. Performing and emotionally surviving
      notifications of death to a patient's family.

PMID- 29172333
TI  - Refusal in the Field. When can an uncooperative patient refuse care and
      transport?

PMID- 29172334
TI  - Homegrown Care. Bulverde Spring Branch (Texas) Fire and EMS offers a unique blend
      of innovative education and MIH-CP.

PMID- 29172335
TI  - Facial Palsy Masquerading as an Acute Dental Abscess.
AB  - Facial nerve palsy has specific symptomology, but varied aetiology. Prompt and
      thorough assessment is required to ascertain if upper or lower motor neurone
      damage has occurred. This report discusses a 6-year-old female, presenting in the
      Emergency Department with unilateral facial weakness. Initially thought to be
      facial swelling relating to her carious dentition, clinical assessment from the
      maxillofacial team identified that the patient had a unilateral facial palsy,
      later diagnosed as Bell's palsy. Her delayed presentation was due to initial
      misdiagnoses in primary care. This case report aims to highlight its aetiology,
      clinical features and appropriate management.  Clinical relevance: To make the
      general dental practitioner aware of different causes of facial paralysis, and to
      provide GDPs with an algorithm to follow in the presentation of a facial palsy in
      the primary care setting.

PMID- 29172336
TI  - The Immune System: Basis of so much Health and Disease: 2. Innate Immunity.
AB  - The immune system is the body's primary defence mechanism against infections, and
      disturbances in the system can cause disease if the system fails in defence
      functions (in immunocompromised people), or if the activity is detrimental to the
      host (as in auto-immune and auto-inflammatory states). A healthy immune system is
      also essential to normal health of dental and oral tissues. This series presents
      the basics for the understanding of the immune system, this article covering
      innate immunity.  Clinical relevance: Modern dental clinicians need a basic
      understanding of the immune system as it underlies health and disease.

PMID- 29172338
TI  - Dentist or Detective?

PMID- 29172337
TI  - Inaccurate Dental Charting in an Audit of 1128 General Dental Practice Records.
AB  - Fourteen dentists at different practices in the UK assessed the dental charts of
      1128 patients who were new to the dentist but not new to the practice; 44% of the
      dental charts were found to be inaccurate. Inaccuracy of the individual practice
      based charts ranged between 16% for the best performing practices to 83% for the
      worst: 5% of dental charts had too many teeth charted and 5% had too few teeth
      charted; 13% of charts had missed amalgam restorations and 18% had missed tooth
      coloured restorations; 5% of charts had amalgam restorations recorded but with
      the surfaces incorrect (eg an MO restoration charted but a DO restoration
      actually present); 9% of charts had tooth-coloured restoration surfaces
      incorrectly recorded. For 7.5% of charts, amalgams were charted but not actually
      present. Other inaccuracies were also noted. The authors reinforce the
      requirements of the GDC, the advice of defence organizations, and the forensic
      importance of accurate dental charts.  Clinical relevance: Dental charting forms
      part of the patient's dental records, and the GDC requires dentists to maintain
      complete and accurate dental records.

PMID- 29172339
TI  - Case report: atypical eruption of lower third molar in a patient who declined
      surgery.

PMID- 29172340
TI  - Treatment of complicated crown or crown-root fracture: some additional
      information.

PMID- 29172341
TI  - Splinting traumatic dental injuries.

PMID- 29172342
TI  - Dear Editor.

PMID- 29172343
TI  - Clinical Challenges Q&A 29. Black eye.

PMID- 29172344
TI  - Technique Tips:  Technique Tips - Use of Interdental Brushes in the Endodontic
      Treatment of Teeth with Wider Canals.

PMID- 29172345
TI  - Own label materials: scientific evidence.

PMID- 29172346
TI  - Antibiotic Guardians: the Role of the Dental Profession.
AB  - The increasing emergence of antibiotic resistance is a major international public
      health problem. As a consequence, it is essential that steps are taken to
      conserve the effectiveness of existing antimicrobial agents. Consumption of
      antibiotics is the prime contributor to the development of resistance. General
      dental practitioners write almost 1 out of 10 prescriptions for antibiotics in
      primary care within the UK and therefore the prudent prescribing of antibiotics
      in dentistry has never been more vital. This paper outlines the impact of
      antimicrobial resistance on modern healthcare, describes the current use of
      antibiotics in general dental practice, and recommends pragmatic ways in which
      dental practitioners can evaluate and optimize their prescribing.  Clinical
      relevance: Dental professionals have a responsibility to both their patients and
      the wider community to prescribe antibiotics appropriately.

PMID- 29172347
TI  - Safe and Sound. Ultrasound as an adjunct for prehospital airway management.

PMID- 29172348
TI  - Dangerous Blasts. Preparing for explosive incident responses.

PMID- 29172349
TI  - EMS 2.0. Time to innovate or renovate?

PMID- 29172350
TI  - Dental Unit Water Lines and their Disinfection and Management: A Review.
AB  - The perceived threat to public health from dental unit water line (DUWL)
      contamination comes from opportunistic and respiratory pathogens such as
      Legionella spp, Nontuberculous Mycobacteria (NTM) and pseudomonads. These
      organisms can grow and multiply in the DUWL biofilm to reach infective
      concentrations, with the potential for inhalation leading to respiratory
      infections or direct contamination of surgical wounds. In this paper we discuss
      current legislation and practical methods for delivering water within the DUWL
      that meets the standards for safety. Clinical relevance: Understanding the
      clinical relevance and methods for decontaminating DUWL is essential to create a
      safe working environment in dentistry.

PMID- 29172351
TI  - Berry Musing: Not Sunk. Laughing is the ultimate act of defiance.

PMID- 29172352
TI  - Complications of an Ageing Dentition Part 1: Occlusal Trauma and Cracked Teeth.
AB  - A growing problem in dentistry is complications associated with failing amalgam
      restorations that have been in place for many years. At present, there is a wide
      variety of treatment options available in the clinician's armamentarium when this
      situation arises, however, without the correct diagnosis, the prognosis for the
      tooth may quickly diminish, despite the clinician's best efforts. A confusing
      array of symptoms and failures may confound even the most experienced dentist,
      which will inevitably lead to invasive and time consuming approaches in a
      desperate attempt to rectify the initial problem. This paper, the first part of a
      three-part series, discusses the possible aetiological factors responsible for
      restoration failure, including occlusal issues and cracks within the tooth
      structure. The second part of the series will focus on restorative options and
      root-treated teeth. The third, and final, part of the series will provide an
      overview of the previous papers and conclude with a case report. Clinical
      relevance: Failure of amalgam restorations is a commonly encountered clinical
      problem in general practice and no one case presents in the same way. A competent
      diagnosis regarding the occlusion and tooth structure, followed with
      implementation of the most appropriate, minimally invasive treatment option,
      requires an adequate knowledge of current literature.

PMID- 29172353
TI  - The Perils of Diagnosing and Treating Overlap Syndrome.
AB  - Autoimmune hepatitis (AIH) may present with clinical, laboratory abnormalitiesand
      histological features suggestive of primary biliary cirrhosis(PBC) or primary
      sclerosing cholangitis (PSC). These variants of AIHare known as overlap
      syndromes. We present a case of a 62 year-old-malewho presented with altered
      liver function tests, anemia and unintentionalweight loss. Initial laboratories
      revealed anemia and a cholestatic pattern. Diagnosticwork-up was remarkable for a
      positive antinuclear antibodies (ANA)test and a liver biopsy suggestive of an AIH
      PBC overlap syndrome. This caseillustrates the complexity of establishing the
      diagnosis and effective therapy inthis condition.

PMID- 29172354
TI  - Diagnosis and Management of Chronic and Aggressive Periodontitis Part 1:
      Periodontal Assessment and Diagnosis.
AB  - common diseases that affect the oral cavity. The differential diagnosis between
      chronic and aggressive periodontitis can be complex for some clinicians and the
      correct diagnosis is a key element in disease management. The three-part series
      will review periodontal clinical assessment and diagnosis, periodontal management
      and finally will discuss two clinical cases. This paper will focus on periodontal
      disease pathogenesis, periodontal clinical assessment and diagnosis. Clinical
      relevance: This paper aims to provide the general dental practitioner with an
      understanding of periodontal disease pathogenesis and to highlight elements in
      the clinical assessment which will help to establish the diagnosis

PMID- 29172355
TI  - Last Word: The Ups and Downs of EMS.

PMID- 29172356
TI  - Early Tooth Loss in Children: A Warning Sign of Childhood Hypophosphatasia.
AB  - Premature exfoliation of primary teeth may be the first manifestation of this
      serious condition and the general dental practitioner plays an important role in
      recognizing dental anomalies and referring patients at an appropriate time. This
      is imperative to ensuring early diagnosis and good quality patient care. This
      article describes the case of a 4-year-old boy affected by childhood
      hypophosphatasia, who presented with premature exfoliation of his primary teeth
      as the first manifestation of this condition. An overview of the condition is
      outlined including a discussion of the likelihood of permanent dentition
      involvement.Clinical relevance: Oral manifestations of hypophosphatasia may be
      the first and the only signs of this condition and may be the basis upon which a
      diagnosis is made.

PMID- 29172357
TI  - The Role of Fibrinolytic Therapy in the Emergency Department.
AB  - Emergency physicians are many times the first-line practitioners to
      encountercirculatory emergencies. Amongst these many diseases we face, of
      importanceare acute myocardial infarction, ischemic cerebrovascular accidents and
      pulmonaryembolism. Familiarity with fibrinolytic agents and regimens, as well as
      indicationsand contraindications, are crucial to the emergency department
      physician.Fibrinolytic therapy has been shown to be beneficial and can serve as a
      bridge todefinite treatment, while lowering the risk of morbidity and mortality.
      Unfortunatelyfibrinolytic therapy is underused and often administered later than
      optimum.The aim of fibrinolytics is to dissolve blood clots that can cause
      serious and potentiallylife-threatening damage if not removed in a timely manner.
      The mechanism ofthis benefit relates to maximizing tissue salvage by early
      restoration of blood flowand thereby enhancing both early and long-term survival.
      Older thrombi haveextensive fibrin polymerization making them more resistant to
      thrombolysis;hence, the importance of early administration of fibrinolytic
      therapy.

PMID- 29172358
TI  - The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.
AB  - The immune system is the body's primary defence mechanism against infections, and
      disturbances in the system can cause disease if the system fails in defence
      functions (in immunocompromised people), or if the activity is detrimental to the
      host (as in auto-immune and auto-inflammatory states). A healthy immune system is
      also essential to normal health of dental and oral tissues. This series presents
      the basics for the understanding of the immune system; this article covers
      adaptive immunity. Clinical relevance: Dental clinicians need a basic
      understanding of the immune system as it underlies health and disease.

PMID- 29172359
TI  - What's New in Dentine Bonding?: Universal Adhesives.
AB  - The ability to bond restorations to dentine successfully is central to minimally
      invasive restorative dentistry. While dentine-bonding agents have gone through a
      variety of 'generations', it is the purpose of this paper to describe the latest
      dentine-bonding agents, the Universal Bonding Agents. These materials may be
      considered 'Universal' insofar as they may be considered to be capable of being
      used for direct and indirect dentistry, as well as being suitable for use in
      whichever etching modality the clinician considers appropriate, namely self-etch,
      etch and rinse or selective enamel etch. Laboratory investigations and initial
      clinical studies hold the promise that Universal Bonding Agents are a forward
      step in the quest for the ultimate bond to tooth substance.Clinical relevance:
      New Universal Bonding Agents appear to present a promising advance in bonding to
      dentine.

PMID- 29172364
TI  - An Update on Current Resuscitation Council (UK) Guidelines.
AB  - On 15 October 2015, The Resuscitation Council (UK) published new resuscitation
      guidelines following the review of resuscitation science by the International
      Liaison Committee on Resuscitation (ILCOR). The 2015 guidelines emphasize the
      importance of interactions between the emergency medical dispatcher, the
      bystander who provides cardiopulmonary resuscitation (CPR) and the prompt
      deployment of an automated external defibrillator (AED); the co-ordination of
      these three elements is crucial to improving out-of-hospital cardiac arrest
      survival. Medical emergencies in dental practices are thought to occur on average
      once every 3-4 years per dentist in primary care. The GDC consider medical
      emergencies as a highly recommended topic for Continuing Professional Development
      (CPD) and recommend at least 10 hours in every CPD cycle. Clinical relevance: The
      publication of the updated guidelines serves as a reminder to the clinical team
      of the importance of being up to date with recognition and treatment of cardiac
      arrest and choking and how seamless interaction between members of both the
      dental and medical teams improves long-term outcomes for patients.

PMID- 29172365
TI  - Psoriasis and Coronary Artery Disease in Hispanics.
AB  - Psoriasis is an immune disorder characterized by chronic activation of
      systemicinflammation. Morbidity and mortality in patients with psoriasis is
      attributedmainly to cardiovascular disease. There are studies in Caucasians and
      African-Americans, but little is known about how psoriasis is associated to
      coronaryartery disease (CAD) in Hispanics. We intend to describe the angiographic
      findingsof a group of Puerto Rican patients with psoriasis. Retrospective cohort
      studyof 46 patients with psoriasis were studied. Coronary angiographic reports
      werereviewed, and collected data was statistically analized. Population median
      agewas 56, and 72% were males. Of the 46 patients, 27 had CAD by
      angiographiccriteria (58.7%). Twelve patients were referred to bypass graft
      surgery, 8 underwentcoronary stent placement, and 7 were treated medically.
      Whether psoriasiscan be considered a risk factor for developing CAD is still on
      debate. Morethan 50% of our patients with psoriasis had angiographic evidence of
      CAD. Adjustingfor traditional cardiovascular risk factors, we found no
      significant association(p>0.05) with CAD. We believe that inflammation plays a
      contributing rolein the increased risk of CAD in these patients. The importance
      of this study relieson being the first retrospective analysis in a group of
      Hispanics trying to determinean association between coronary artery disease and
      psoriasis when in PuertoRico, coronary artery disease is 30% less than in the
      United States.

PMID- 29172366
TI  - Dietary Advice - Getting the Message Across.
AB  - Providing dietary advice to our patients forms the cornerstone of prevention for
      many dental diseases. However, simply prescribing information is unlikely to
      bring about long-term behavioural change. This article explores the theory of
      health behaviour as well as ways in which we can 'get the message
      across'.Clinical relevance: Prescriptive approaches to behaviour changes can be
      considered inconsistent and ineffective. This article explores more patient
      centred methods of inducing behaviour change with regard to dietary advice in the
      general dental practice setting.

PMID- 29172367
TI  - Clinical Challenges Q&A 30. Red Skin.

PMID- 29172368
TI  - Technique Tips:  Technique Tips - An Innovative Prosthetic Design for the
      Replacement of Missing Anterior Teeth.

PMID- 29172369
TI  - Cerebrospinal Fluids Leaks of the Cranial Vault Management with Compression Cap:
      Case Series.
AB  - Cerebrospinal fluid leaks of the cranial vault, constitute one of the most
      commoncomplications after neurosurgical procedures. In this paper we introduce
      toyou an observational study, in which a series of patients with this
      complicationwhere managed by using elastic compression hat during 18 hours per
      day,for two weeks to four months. Every one of them presented complete
      resolutionof the leak, without any recurrence until actual controls. After that
      we perform areview of the literature, demonstrating this is a new therapeutic
      management,being us the first group on reporting it. According to the observed
      results, it wasconcluded that despite more studies are required, the use of
      elastic compressionhats for this kind of patients could be effective and safe.

PMID- 29172370
TI  - Previous Exposure to Anesthesia and Autism Spectrum Disorder (ASD): A Puerto
      Rican Population-Based Sibling Cohort Study.
AB  - BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by impaired social
      interactionand communication, and by restricted and repetitive behavior, that
      beginsusually before a child is three yearsold.(1) Researchers have shown that
      prevalencerates in the U.S. may be as high as 1 in 68.(52) A number of studies
      haveexamined the effects of early exposure to anesthesia on brain development
      andsubsequent impairment in neurocognitive function; yet, little is known
      aboutthe possible effects of anesthetic agents on social-behavioral functioning.
      Theassociation between exposure to anesthesia either in uterus, during the
      firstyears of life, or later and development of Autistic Spectrum Disorder (ASD)
      or itsseverity was determined in a retrospective population based cohort study.
      OBJECTIVES: Identify if children who had previous exposureto anesthesia either in
      uterus, first years of life during their developing brainyears, or later, are at
      risk of developing ASD and its severe form of the disease. METHODS: Data was
      obtained from structured interviews administered to a sample of
      515parents/guardians distributed in two groups: ASD = 262 children diagnosedwith
      this condition and Non-ASD: 253 children (siblings of ASD group) withoutdiagnosis
      (95% confidence interval) that freely decided to participate and agreedto a
      consent form. Variables studied include: demographics, diagnosis andseverity of
      ASD, exposure to anesthesia, method of childbirth, and age of exposureChildren
      less than 2 years of age were considered into have developingbrain period. Data
      was analyzed using Chi-square or Fisher exact test. RESULTS: In contrast to non
      ASD group, most of the children within ASD group weremale, 76% (p=0.0001). With
      regards to methods of childbirth, 64% of the ASDpopulation were vaginal delivery
      (VD; Non-anesthesia exposure group) and36% cesarean delivery (CD) compared to non
      autistic population with 71%VD and 29% CD, which demonstrates no statistical
      difference between bothgroups (p=0.1113). Out of the 36% of ASD population that
      underwent CD,7% were performed using general anesthesia and 93% regional
      anesthesia,while the 29% of the CD of non-ASD, 5% were performed using general
      anesthesiaand 95% regional anesthesia. This reveals no statistical
      significance(p=0.7569) with the development of ASD and the type of anesthesia
      usedwhen comparing ASD with non-ASD patients. In view of severity of autism,
      inVD, 56% of ASD population had mild form of the disorder, 34% moderate, and10%
      severe; while CD had a 54% mild form of the disorder, 33% moderate, and13%
      severe. This shows no statistical association (p=0.8069) when comparingexposure
      to anesthesia in uterus to subsequent severe form of ASD.Of the 262 ASD patients,
      99 had exposure to anesthetics before their diagnosis,while in Non-ASD
      population, 110 had exposure to anesthesia, demonstratingno statistically
      significant association between both groups (p=0.2091).Out of 99 ASD patients
      exposed to anesthesia prior to their diagnosis, 72 wereexposed before age 2. When
      compared to the 110 Non-ASD patients exposedto anesthesia, 86 had exposure during
      this developing brain period, which indicatesno statistically significant
      association (p=0.4207). In addition, most ofthe ASD children exposed to
      anesthesia during developing brain were diagnosedwith mild degree of the disorder
      when compared to ASD children withoutany previous exposure to anesthesia
      (p=0.9700) during the same period.When the exposure occurred after age 2, ASD
      children developed mild formof the disorder as compared with ASD children without
      any previous exposureto anesthesia (p=0.1699) in that period. CONCLUSIONS:
      Children under early exposure to anesthesia in uterus, first 2 years of life, or
      later are not more likely to develop neither ASD nor severe form of the disorder.

PMID- 29172371
TI  - Analysis of clinical characteristics of dialysis patients at the University
      Hospital.
AB  - OBJECTIVES: The incidence and prevalence of Chronic Kidney Disease (CKD)patients
      treated with dialysis has continued to increase worldwide. These patientsare at
      the highest risk of developing cardiovascular complications whichcontribute to
      their demise. The objective of this study was to describe the clinicaland
      demographic characteristics of the patients on maintenance hemodialysisat the
      University Hospital, in San Juan Puerto Rico. METHODS: We reviewed a total of 55
      active patients. Data was collected toidentify the demographic and clinical
      characteristics. Co-morbid conditionssuch as diabetes mellitus, hypertension, and
      coronary artery disease (CAD)were noted as well as age, dialysis vintage and
      social and educational profiles. RESULTS: Patients were divided into two groups
      according to age (group 1 wereless than 60 years and group 2 were more than 60
      years). Average age was 42 yearsin group 1 with 17 females and 24 males and 78
      years in group 2 with 6 femalesand 8 males. Diabetes mellitus was present in 17
      (41%) of group 1 and 5 patients(35%) of group 2. Likewise hypertension was
      present in 26 (63%) of group 1 patientsand 11(78%) of group 2 patients. CAD was
      present in 15 (36%) of group 1patients and 7 (50%) of group 2 patients. There was
      an association between lowannual income in both groups but not in the level of
      education. CONCLUSION: A relatively young population was identified in our
      descriptiveanalysis of hemodialysis patients at the University Hospital. The
      expected highincidence of diabetes mellitus observed in the general population of
      hemodialysispatients in our country was not present. Hypertension and CAD
      weremajor risk factors in these patients. In view of these findings we
      recommendbetter control of blood pressure, prevention and early detection of CAD
      inCKD patients before initiating dialysis.

PMID- 29172372
TI  - ?

PMID- 29172373
TI  - ?

PMID- 29172374
TI  - False Dawns and New Horizons in Patient Safety Research and Practice.
AB  - In response to a weight of evidence that patients are frequently harmed as a
      result of their care, there have been concerted efforts to make healthcare safer,
      with health systems across the globe investing significant resources in policies
      and programmes designed to reduce adverse events. Yet, despite extensive efforts,
      improvements in safety have proved difficult to sustain and spread, with studies
      confirming there has been no measurable, systems-level improvement in the overall
      rates of preventable harm. Here, we highlight the limitations of the thinking
      which underpins current efforts to make healthcare systems safer and point to new
      and emerging approaches to understanding and addressing patient safety in
      complex, dynamic health systems.

PMID- 29172375
TI  - Governing Collaborative Healthcare Improvement: Lessons From an Atlantic Canadian
      Case.
AB  - The Atlantic Healthcare Collaboration for Innovation and Improvement in Chronic
      Disease (AHC) Quality Improvement Collaborative (QIC) in Eastern Canada provided
      an approach to spur system-level reform across multiple health systems for
      patients and families living with chronic disease. Developed and led by senior
      executives with a unique governance approach and involving clinical front-line
      teams, the AHC serves as a practical example of leadership creating and driving
      momentum for achieving success in collaborative health system improvements.

PMID- 29172376
TI  - Does Scale of Public Hospitals Affect Bargaining Power? Evidence From Japan.
AB  - BACKGROUND: Many of public hospitals in Japan have had a deficit for a long time.
      Japanese local governments have been encouraging public hospitals to use group
      purchasing of drugs to benefit from the economies of scale, and increase their
      bargaining power for obtaining discounts in drug purchasing, thus improving their
      financial situation. In this study, we empirically investigate whether or not the
      scale of public hospitals actually affects their bargaining power. METHODS: Using
      micro-level panel data on public hospitals, we examine the effect of the scale of
      public hospitals (in terms of the number of occupancy beds) on drug purchasing
      efficiency (DPE) (the average discount rate in purchasing drugs) as a proxy
      variable of the bargaining power. Additionally, we evaluate the effect of the
      presence or absence of management responsibility in public hospital for economic
      efficiency as the proxy variable of an economic incentive and its interaction
      with the hospital scales on the bargaining power. In the estimations, we use the
      fixed effects model to control the heterogeneity of each hospital in order to
      estimate reliable parameters. RESULTS: The scale of public hospitals does not
      positively correlate with bargaining power, whereas the management responsibility
      for economic efficiency does. Additionally, scale does not interact with
      management responsibility. CONCLUSION: Giving management responsibility for
      economic efficiency to public hospitals is a more reliable way of gaining
      bargaining power in drug purchasing, rather than promoting the increase in scale
      of these public hospitals.

PMID- 29172377
TI  - Should Employers Be Permitted not to Hire Smokers? A Review of US Legal
      Provisions.
AB  - BACKGROUND: Increasingly, healthcare and non-healthcare employers prohibit or
      penalize the use of tobacco products among current and new employees in the
      United States. Despite this trend, and for a range of different reasons, around
      half of states currently legally protect employees from being denied positions,
      or having employment contracts terminated, due to tobacco use. METHODS: We
      undertook a conceptual analysis of legal provisions in all 50 states. RESULTS: We
      found ethically relevant variations in terms of how tobacco is defined, which
      employee populations are protected, and to what extent they are protected.
      Furthermore, the underlying ethical rationales for smoker protection differ, and
      can be grouped into two main categories: prevention of discrimination and
      protection of privacy. CONCLUSION: We critically discuss these rationales and the
      role of their advocates and argue that enabling equality of opportunity is a more
      adequate overarching concept for preventing employers from disadvantaging
      smokers.

PMID- 29172378
TI  - How Are New Vaccines Prioritized in Low-Income Countries? A Case Study of Human
      Papilloma Virus Vaccine and Pneumococcal Conjugate Vaccine in Uganda.
AB  - BACKGROUND: To date, research on priority-setting for new vaccines has not
      adequately explored the influence of the global, national and sub-national levels
      of decision-making or contextual issues such as political pressure and
      stakeholder influence and power. Using Kapiriri and Martin's conceptual
      framework, this paper evaluates priority setting for new vaccines in Uganda at
      national and sub-national levels, and considers how global priorities can
      influence country priorities. This study focuses on 2 specific vaccines, the
      human papilloma virus (HPV) vaccine and the pneumococcal conjugate vaccine (PCV).
      METHODS: This was a qualitative study that involved reviewing relevant Ugandan
      policy documents and media reports, as well as 54 key informant interviews at the
      global level and national and sub-national levels in Uganda. Kapiriri and
      Martin's conceptual framework was used to evaluate the prioritization process.
      RESULTS: Priority setting for PCV and HPV was conducted by the Ministry of Health
      (MoH), which is considered to be a legitimate institution. While respondents
      described the priority setting process for PCV process as transparent,
      participatory, and guided by explicit relevant criteria and evidence, the
      prioritization of HPV was thought to have been less transparent and less
      participatory. Respondents reported that neither process was based on an explicit
      priority setting framework nor did it involve adequate representation from the
      districts (program implementers) or publicity. The priority setting process for
      both PCV and HPV was negatively affected by the larger political and economic
      context, which contributed to weak institutional capacity as well as power
      imbalances between development assistance partners and the MoH. CONCLUSION:
      Priority setting in Uganda would be improved by strengthening institutional
      capacity and leadership and ensuring a transparent and participatory processes in
      which key stakeholders such as program implementers (the districts) and
      beneficiaries (the public) are involved. Kapiriri and Martin's framework has the
      potential to guide priority setting evaluation efforts, however, evaluation
      should be built into the priority setting process a priori such that information
      on priority setting is gathered throughout the implementation cycle.

PMID- 29172379
TI  - New Health Technologies: A UK Perspective Comment on "Providing Value to New
      Health Technology: The Early Contribution of Entrepreneurs, Investors, and
      Regulatory Agencies".
AB  - New health technologies require development and evaluation ahead of being
      incorporated into the patient care pathway. In light of the recent publication by
      Lehoux et al who discuss the role of entrepreneurs, investors and regulators in
      providing value to new health technologies, we summarise the processes involved
      in making new health technologies available for use in the United Kingdom.

PMID- 29172380
TI  - This Is My (Post) Truth, Tell Me Yours Comment on "The Rise of Post-truth
      Populism in Pluralist Liberal Democracies: Challenges for Health Policy".
AB  - This is a commentary on the article 'The rise of post-truth populism in pluralist
      liberal democracies: challenges for health policy.' It critically examines two of
      its key concepts: populism and 'post truth.' This commentary argues that there
      are different types of populism, with unclear links to impacts, and that in some
      ways, 'post-truth' has resonances with arguments advanced in the period at the
      beginning of the British National Health Service (NHS). In short, 'post-truth'
      populism' may be 'deja vu all over again,' and there are multiple (post) truths:
      this is my (post) truth, tell me yours.

PMID- 29172381
TI  - Innovative Use of the Law to Address Complex Global Health Problems Comment on
      "The Legal Strength of International Health Instruments - What It Brings toGlobal
      Health Governance?"
AB  - Addressing the increasingly globalised determinants of many important problems
      affecting human health is a complex task requiring collective action. We suggest
      that part of the solution to addressing intractable global health issues indeed
      lies with the role of new legal instruments in the form of globally binding
      treaties, as described in the recent article of Nikogosian and Kickbusch.
      However, in addition to the use of international law to develop new treaties,
      another part of the solution may lie in innovative use of existing legal
      instruments. A 2015 court ruling in The Hague, which ordered the Dutch government
      to cut greenhouse gas emissions by at least 25% within five years, complements
      this perspective, suggesting a way forward for addressing global health problems
      that critically involves civil society and innovative use of existing domestic
      legal instruments.

PMID- 29172382
TI  - Ensuring HIV Data Availability, Transparency and Integrity in the MENA Region
      Comment on "Improving the Quality and Quantity of HIV Data in the Middle East and
      North Africa: Key Challenges and Ways Forward".
AB  - In this commentary, we elaborate on the main points that Karamouzian and
      colleagues have made about HIVdata scarcity in Middle Eastern and North African
      (MENA) countries. Without accessible and reliable data, no epidemic can be
      managed effectively or efficiently. Clearly, increased investments are needed to
      bolster capabilities to capture and interpret HIV surveillance data. We believe
      that this enhanced capacity can be achieved, in part, by leveraging and
      repurposing existing data platforms, technologies and patient cohorts. An
      immediate modest investment that capitalizes on available infrastructure can
      generate data on the HIV burden and spread that can be persuasive for MENA policy
      makers to intensify efforts to track and contain the growing HIV epidemic in this
      region. A focus on key populations will yield the most valuable data, including
      among men who have sex with men (MSM), transgender women and men, persons who
      inject drugs (PWIDs), female partners of high risk men and female sex workers.

PMID- 29172383
TI  - Should Priority Setting Also Be Concerned About Profound Socio-Economic
      Transformations? A Response to Recent Commentary.

PMID- 29172384
TI  - Posterior Cruciate Ligament Reconstruction and Posterolateral Corner Injury.

PMID- 29172385
TI  - Single-Bundle versus Double-Bundle Posterior Cruciate Ligament Reconstruction: A
      Meta-Analysis of Randomized Controlled Trials.
AB  - Purpose: This meta-analysis evaluated the benefits of single-bundle (SB) and
      double-bundle (DB) surgical techniques for posterior cruciate ligament
      reconstruction (PCLR) in terms of clinical outcomes. Methods: Five electronic
      databases were searched for relevant articles published until September 2016.
      Clinical outcomes of both techniques were evaluated using Lysholm knee function
      scores, Tegner activity scores, side-to-side differences, and International Knee
      Documentation Committee (IKDC) objective grades. The results are presented as a
      risk ratio (RR) for binary outcomes and a weighted mean difference (WMD) for
      continuous outcomes with a 95% confidence interval (CI). Results: Four randomized
      controlled trials (RCTs) were included. There were no significant differences in
      the Lysholm knee function scores (WMD=1.63; 95% CI, 0.00 to 3.27; I2=0%), Tegner
      activity scores (WMD=0.17; 95% CI, -0.08 to 0.43; I2=20%), side-to-side
      differences (WMD=-0.97; 95% CI, -2.41 to 0.47; I2=78%), and IKDC objective grades
      (RR=1.18; 95% CI, 1.00 to 1.39; I2=0%) at the final follow-up. Conclusions: The
      present study demonstrates that both SB and DB techniques for PCLR are comparable
      in terms of restoration of knee stability and improvement of knee function.
      However, it is still unclear which technique yields better clinical outcomes. To
      verify and further corroborate our results, more larger-scale, high-quality RCTs
      are encouraged.

PMID- 29172387
TI  - Comparison of an Accelerometer-Based Portable Navigation System, Patient-Specific
      Instrumentation, and Conventional Instrumentation for Femoral Alignment in Total
      Knee Arthroplasty.
AB  - Purpose: The KneeAlign2 (KA2, OrthoAlign Inc.) accelerometer-based portable
      navigation system and patient-specific instrumentation (PSI; Signature,
      ZimmerBiomet) are widely used for ideal femoral component alignment in total knee
      arthroplasty (TKA). However, there has been no comparative study of the KA2
      system, PSI, and conventional intramedullary instrumentation (CON). The purpose
      of this study was to compare the accuracy in achieving proper femoral component
      alignment and clinical features by using the KA2 navigation system, PSI, and CON.
      Materials and Methods: We retrospectively compared the accuracy of femoral
      component alignment of 34 TKAs performed with the KA2 system for implantation of
      the femoral component, 32 TKAs with PSI, and 33 TKAs with CON. Results: In the
      coronal plane, use of the KA2 system was more likely to result in optimal femoral
      component alignment than the CON and PSI (p<0.01). In the sagittal plane, use of
      the KA2 system was more likely to result in optimal component alignment than PSI,
      but the difference between the KA2 and CON was insignificant. Conclusions: The
      portable accelerometer-based KA2 navigation system enabled ideal femoral
      implantation in the coronal and sagittal planes, as compared to the PSI or CON.

PMID- 29172386
TI  - Current Concepts of Posterolateral Corner Injuries of the Knee.
AB  - The number of posterolateral corner (PLC) injury patients has risen owing to the
      increased motor vehicle accidents and sports activities. Careful examination is
      required because this injury is easy to overlook and may lead to chronic
      instability. The purpose of this article is to review the anatomy, biomechanics,
      diagnosis, classification and, treatment of PLC injuries and summarize the recent
      literatures regarding the treatment outcomes.

PMID- 29172388
TI  - Does Combination Therapy of Popliteal Sciatic Nerve Block and Adductor Canal
      Block Effectively Control Early Postoperative Pain after Total Knee Arthroplasty?
AB  - Purpose: We compared adductor canal block (ACB) alone and a combination of ACB
      and sciatic nerve block (SNB) to control early postoperative pain after total
      knee arthroplasty. Materials and Methods: One hundred patients received
      continuous ACB alone (group A), and another 100 patients received continuous ACB
      and single popliteal SNB (group B). Pain was evaluated at rest and 45 degrees 
      knee flexion using the numeric rating scale (NRS). The number of times the
      patient pressed the intravenous patient-controlled analgesia (PCA) button, total
      PCA volume infused, and the total dosage of additional analgesics were evaluated.
      We also investigated complications associated with each pain control technique.
      Results: The NRS score on postoperative day 1 was significantly lower in group B
      than in group A. The number of times patients pressed the PCA button on
      postoperative day 1 and the total infused volume were significantly lower in
      group B than in group A. Thirty-five (35%) patients in group B developed foot
      drop immediately after surgery; but they all fully recovered on postoperative day
      1. Conclusions: SNB can be effective for management of early postoperative pain
      that persists even after ACB. Further research is needed to determine the proper
      dosage and technique for reducing the incidence of foot drop.

PMID- 29172389
TI  - Full Cementation in Revision Total Knee Arthroplasty Using a Constrained Condylar
      Knee Prosthesis with an Average 7-Year Follow-up.
AB  - Purpose: To evaluate clinical and radiological outcome of the full cementation
      technique in revision total knee arthroplasty (TKA) using a constrained condylar
      knee (CCK) prosthesis. Materials and Methods: Between January 2008 and March
      2012, 18 cases (16 patients) of fully cemented revision TKA were performed using
      a CCK prosthesis. Fifteen cases of aseptic loosening (13 patients) and 3 cases of
      infection were included. There were 2 males and 14 females with a mean age of
      76.7 years at the time of surgery, and the average follow-up was 81 months.
      Clinically, the pain score, function score and Hospital for Special Surgery (HSS)
      score were evaluated. Radiologically, loosening, radiolucent lines and migration
      of implant were evaluated. Results: Preoperatively, the pain score, function
      score and HSS score were 50.3, 24.4 and 61.8 points, respectively. At the latest
      follow-up, the scores were improved to 84.8, 63.6 and 85.6 points, respectively
      (p<0.05). Loosening or migration of implant was not observed in any cases.
      Radiolucent lines were observed in 5 cases underneath the tibial component
      without progression during the follow-up. Conclusions: The full cementation
      technique in revision TKA using a CCK showed excellent clinical results. Although
      radiolucent lines were observed in 27.8% underneath the tibial component, there
      was no progression to loosening or instability.

PMID- 29172390
TI  - Meniscal Extrusion Progresses Shortly after the Medial Meniscus Posterior Root
      Tear.
AB  - Purpose: Medial meniscus posterior root tears (MMPRT) induce medial meniscus
      extrusion (MME). However, the time-dependent extent of MME in patients suffering
      from the MMPRT remains unclear. This study evaluated the extent of MME after
      painful popping events that occurred at the onset of the MMPRT. Materials and
      Methods: Thirty-five patients who had an episode of posteromedial painful popping
      were investigated. All the patients were diagnosed as having an MMPRT by magnetic
      resonance imaging (MRI) within 12 months after painful popping. Medial meniscus
      body width (MMBW), absolute MME, and relative MME (100*absolute MME/MMBW) were
      assessed among three groups divided according to the time after painful popping
      events: early period (<1 month), subacute period (1-3 months), and chronic period
      (4-12 months). Results: In the early period, absolute and relative MMEs were 3.0
      mm and 32.7%, respectively. Absolute MME increased up to 4.2 mm and 5.8 mm during
      the subacute and chronic periods, respectively. Relative MME also progressed to
      49.2% and 60.3% in the subacute and chronic periods, respectively. Conclusions:
      This study demonstrated that absolute and relative MMEs increased progressively
      within the short period after the onset of symptomatic MMPRT. Our results suggest
      that early diagnosis of an MMPRT may be important to prevent progression of MME
      following the MMPRT.

PMID- 29172392
TI  - Arthroscopic Pullout Fixation for a Small and Comminuted Avulsion Fracture of the
      Posterior Cruciate Ligament from the Tibia.
AB  - We describe a patient who underwent arthroscopic pullout fixation for a posterior
      cruciate ligament (PCL) avulsion fracture. A 46-year-old female, injured in a
      fall while riding a motorcycle, was diagnosed with a right knee PCL tibial
      attachment avulsion fracture and underwent arthroscopic osteosynthesis. A
      Kirschner wire was drilled to a point just medial to the medial border of the
      anterior tibial bony bed. A suture wire was folded into a loop and introduced
      into the posteromedial compartment via the bone tunnel. A fixation thread was
      inserted from the posteromedial portal, through the medial and lateral loop
      wires, and into the posteromedial compartment. The lateral and medial loop wires
      attached to the thread were pulled to the outside, and the thread was fixed onto
      the tibia. Three months post-surgery, she returned to her job. This procedure
      represents a minimally invasive method of treating avulsion fractures of the
      tibial attachment of the PCL.

PMID- 29172391
TI  - Measurement of Knee Rotation Angles Using a Smartphone Application: An
      Experimental Study of Porcine Knees.
AB  - Purpose: This study evaluated the efficacy of a smartphone application in the
      measurement of rotation angles in porcine knees. Materials and Methods: Two K
      wires were fixated to the femoral condyle and anterior tibial crest of 10 porcine
      legs. The angle created between the K-wires with an external rotation force
      applied was measured on a photograph and defined as the true angle. The same
      force was applied to the legs placed on a splint with a smartphone attached to
      the plantar side. The angle presented on a smartphone application was determined
      as the measured angle. The differences between the true and measured angles in 30
      degrees  and 90 degrees  knee flexion and differences in measured angles
      depending on the status of the popliteus tendon were compared. Results: In the
      intact knees, the mean true angles in 30 degrees  and 90 degrees  flexion were
      20.5 degrees +/-1.4 degrees  and 19.1 degrees +/-1.3 degrees , respectively, and
      the mean measured angles in 30 degrees  and 90 degrees  flexion were 21.1 degrees
      +/-0.9 degrees  and 18.6 degrees +/-1.6 degrees , respectively. When the
      popliteus tendon was cut, the mean true angles in 30 degrees  and 90 degrees 
      flexion were 31.4 degrees +/-1.1 degrees  and 38.5 degrees +/-2.5 degrees ,
      respectively, and the mean measured angles in 30 degrees  and 90 degrees  flexion
      were 31.8 degrees +/-1.2 degrees  and 39.2 degrees +/-2.8 degrees , respectively.
      The differences between the true and measured angles were not significant. The
      measured angle increased by more than 10 degrees  after cutting of the popliteus
      tendon in both 30 degrees  and 90 degrees  flexion. Conclusions: Using a
      smartphone application could be a good method of measuring knee rotation.

PMID- 29172393
TI  - The Meniscofemoral Ligament Mimicking a Lateral Meniscus Tear.
AB  - A 58-year-old male patient who had developed left knee pain with a history of
      trauma was referred to our hospital. Physical examination and further examination
      by magnetic resonance imaging revealed results that closely resemble a horizontal
      tear of the lateral meniscus and a tear of the medial meniscus. Arthroscopically,
      we found a cord-like structure originating from the posterior 1/3 portion of the
      lateral meniscus and passing obliquely toward the medial femoral condyle in front
      of the posterior cruciate ligament without a tear of the lateral meniscus. In
      this report, we describe a rare case of anterior meniscofemoral ligament that was
      clearly seen on arthroscopy and mimicked a meniscal tear, which is also known as
      a pseudo-tear of the meniscus.

PMID- 29172394
TI  - Subchondral Insufficiency Fracture in the Lateral Compartment of the Knee in a 64
      Year-Old Marathon Runner.
AB  - A 64-year-old marathon runner presented to our clinic with a history of worsening
      pain in her left knee. Following magnetic resonance imaging, the diagnosis of
      subchondral insufficiency fracture of the knee (SIFK) was made. A course of
      conservative management via bisphosphonates was initiated. The patient
      successfully recovered and returned to full athletic function, having recently
      returned to competitive marathon running. This article aims to present this
      unusual case of lateral compartment SIFK and summarise the literature on this
      uncommon condition.

PMID- 29172395
TI  - The Clinicopathological and Prognostic Significance of the Gross Classification
      of Hepatocellular Carcinoma.
AB  - BACKGROUND: We aimed to determine the clinicopathological significance of the
      gross classification of hepatocellular carcinoma (HCC) according to the Korean
      Liver Cancer Association (KLCA) guidelines. METHODS: A retrospective analysis was
      performed on 242 cases of consecutively resected solitary primary HCC between
      2003 and 2012 at Seoul National University Bundang Hospital. The gross
      classification (vaguely nodular [VN], expanding nodular [EN], multinodular
      confluent [MC], nodular with perinodular extension [NP], and infiltrative [INF])
      was reviewed for all cases, and were correlated with various clinicopathological
      features and the expression status of "stemness"-related (cytokeratin 19 [CK19],
      epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition
      (EMT)-related (urokinase plasminogen activator receptor [uPAR] and Ezrin)
      markers. RESULTS: Significant differences were seen in overall survival (p=.015)
      and disease-free survival (p = .034) according to the gross classification; INF
      type showed the worst prognosis while VN and EN types were more favorable. When
      the gross types were simplified into two groups, type 2 HCCs (MC/NP/INF) were
      more frequently larger and poorly differentiated, and showed more frequent
      microvascular and portal venous invasion, intratumoral fibrous stroma and higher
      pT stages compared to type 1 HCCs (EN/VN) (p<.05, all). CK19, EpCAM, uPAR, and
      ezrin expression was more frequently seen in type 2 HCCs (p<.05, all). Gross
      classification was an independent predictor of both overall and disease-free
      survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118;
      95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard
      ratio, 1.617; 95% confidence interval, 1.092 to 2.394). CONCLUSIONS: The gross
      classification of HCC had significant prognostic value and type 2 HCCs were
      associated with clinicopathological features of aggressive behavior, increased
      expression of "stemness"- and EMT-related markers, and decreased survival.

PMID- 29172397
TI  - Favorable effect of corticosteroids in treating acute-on-chronic liver failure
      underlying chronic hepatitis B.
AB  - Acute-on-chronic liver failure (ACLF) occurs in the presence of a chronic liver
      disease or cirrhosis, and often results from exacerbation of chronic hepatitis B
      (CHB). The efficacy of corticosteroid treatment in ACLF patients with underlying
      CHB remains unclear. We report the case of a 50-year-old woman who experienced
      ACLF due to CHB exacerbation and was treated with a combination of
      corticosteroids and nucleot(s)ide analogue (NUC). The patient showed rapid
      decompensation due to CHB exacerbation. Three months of antiviral therapy
      produced no improvement in liver function. Combination therapy with
      corticosteroids and NUC was started, which did result in improvement of liver
      function. This case shows that the combined therapy of corticosteroids and NUC
      can be effective in treating ACLF due to CHB exacerbation.

PMID- 29172396
TI  - The Effect of Endoscopic Tympanoplasty on Cochlear Function.
AB  - OBJECTIVES: The aim of this prospective clinical study was to measure the
      audiologic outcomes of the patients that underwent endoscopic transcanal
      cartilage tympanoplasty, and to investigate the effects on cochlear function.
      METHODS: Thirty-three patients (33 ears) who were diagnosed with noncomplicated
      chronic otitis media and underwent endoscopic transcanal cartilage tympanoplasty
      technique were included. Pre- and postoperative first month distortion product
      otoacoustic emission (DPOAE) signal-to-noise ratio (SNR), bone conduction hearing
      levels and air bone gap (ABG) values were measured and total endoscope usage time
      was noted. RESULTS: Preoperative median SNR measurements at 0.5, 1, 2, and 4 kHz
      were 6 dB (1-11; interquartile range [IQR], 1), 6 dB (4-20; IQR, 1), 7 dB (3-26;
      IQR, 5) and 5.50 dB (0-9; IQR, 3), respectively. Postoperative median SNR
      measurements at 0.5, 1, 2, and 4 kHz were 6 dB (3-9; IQR, 1), 6 dB (2-21; IQR,
      3), 7 dB (2-20; IQR, 3), and 6 dB (0-10; IQR, 7), respectively. Regarding the
      DPOAE measurements, there was no statistically significant difference between the
      SNR values of all given frequencies (P>0.05). Regarding the pure tone audiometry
      (PTA) measurements, bone conduction was significantly better at 0.5 and 1 kHz,
      postoperatively (P<0.05) and there was statistically significant difference at 2
      and 4 kHz (P>0.05). Additionally, no statistically significant correlation was
      found between the SNR and PTA measurements and the endoscope usage time (P>0.05).
      CONCLUSION: We suggested that cochlear functions and sensorineural hearing
      remained stable after endoscopic transcanal cartilage tympanoplasty and cold
      light source doesn't cause significant adverse effects cochlear functions.

PMID- 29172398
TI  - The evaluation of cellular immune function in elderly patients with systemic
      lupus erythematosus.
AB  - Background/Aims: To evaluate cellular immune function in systemic lupus
      erythematosus (SLE) patients over 60 years old, the association between
      antinuclear antibody (ANA) titers and the ratio of CD4+ /CD8+ was analyzed in
      this study. The distribution of ANAs and extractable nuclear antibodies (ENAs) in
      a healthy elderly population was also investigated. Methods: Serum ANA titers
      were assayed by indirect immunofluorescence (IIF) and the CD4+ /CD8+ T-cell ratio
      was determined by flow cytometry in 76 SLE patients and 30 healthy control
      individuals. IIF of cytoplasm and nuclear and nucleolar staining were performed
      on samples taken from 286 healthy elderly individuals. ENA levels were determined
      using a strip enzyme immunoassay among patients that tested positive for ANAs.
      Results: ANA titers were negative in the 30 control individuals, but were
      positive in the 76 SLE patients. Based on ANA titers, the SLE patients were
      stratified to low (<= 1:320), medium (1:640 to 1:1,280), and high (>= 1:2,560)
      titer groups. The average CD4+ /CD8+ ratio of the SLE group was significantly
      lower than that of the control group. Among the 286 healthy elderly volunteers,
      59 (20.63%) tested positive for ANAs. A homogeneous pattern was present in 47.46%
      of those 59 patients and a granule pattern in the karyoplasm was present in
      33.90%. Furthermore, of the 59 patients, ENAs immunoassay was positive in 18
      (30.51%); Sjogren syndrome-related antigen A (SSA)/52 kd and Sjogren syndrome
      antigen B (SSB)/La were the two major antibodies. Conclusions: The significantly
      lower CD4+ /CD8+ ratio among SLE patients over 60 years old is associated with
      deregulated immune responses and the development of SLE. A low ANA titer (1:160)
      is common in healthy elders, emphasizing the importance of considering age when
      determining if the evaluation of ANA titers is to be included in autoimmune
      disease diagnosis.

PMID- 29172399
TI  - Methylprednisolone versus intravenous immune globulin as an initial therapy in
      adult primary immune thrombocytopenia.
AB  - Background/Aims: Few studies have addressed whether there are differences in
      clinical efficacy between intravenous methylprednisolone (methyl-Pd) and
      intravenous immunoglobulin (IVIg) use. Methods: We retrospectively compared
      platelet responses and toxicities associated with these two treatments in adult
      patients with immune thrombocytopenia. Patients received intravenous methyl-Pd
      therapy followed by oral prednisolone (Pd) from 1993 to 2002 and IVIg together
      with oral Pd from 2003 to 2008. Results: Early response and maintenance of the
      response were assessed at 7 days and 6 months after treatment, respectively. Of
      the 87 patients enrolled, 77 (88.5%) were eligible for analysis. Early responses
      occurred in 30 of 39 patients (76.9%) receiving methyl-Pd versus 33 of 38
      patients (86.6%) receiving IVIg (p = 0.187). The response was maintained in 28
      patients (71.8%) in the methyl-Pd arm and in 23 patients (60.5%) in the IVIg arm
      (p = 0.187). The time to a complete response in the IVIg arm (6 days; range, 1 to
      35) was shorter than that in the methyl-Pd arm (13.5 days; range, 2 to 29) (p =
      0.002). Side effects were mild and tolerable in both arms. Five years after
      initiating treatment, 7 of 18 patients (38.9%) and five of 14 patients (35.7%)
      were still maintaining a response in the methyl-Pd and IVIg arms, respectively.
      Conclusions: These results indicate that neither the early response rate nor the
      long-term outcome differed between the methyl-Pd and IVIg treatments. However,
      IVIg induced a complete response more rapidly than did methyl-Pd.

PMID- 29172400
TI  - Development, validation, and application of a novel tool to measure disease
      related knowledge in patients with inflammatory bowel disease.
AB  - Background/Aims: The Crohn's and Colitis Knowledge (CCKNOW) score does not
      reflect updated knowledge relating to inflammatory bowel disease (IBD). The aim
      of this study was to develop, validate, and apply a novel tool to measure disease
      related knowledge in IBD patients. Methods: A questionnaire composed of 24 items
      regarding knowledge of IBD was developed: Inflammatory Bowel Disease Knowledge
      (IBD-KNOW). Discriminate ability of IBD-KNOW was validated in three occupational
      groups (14 doctors, 20 nurses, and 19 clerks). The CCKNOW and IBD-KNOW were
      administered to IBD patients. Factors affecting the level of IBD-related
      knowledge were analyzed. Results: The median Inflammatory Bowel Disease Knowledge
      (IBD-KNOW) score was significantly different among the three groups for
      validation (22 doctors, 20 nurses, and five clerks; p < 0.001). The IBD-KNOW
      showed excellent internal consistency (Cronbach alpha = 0.952) and high
      correlation with CCKNOW (Spearman rho = 0.827, p = 0.01). A total of 200 IBD
      patients (120 Crohn's disease, 80 ulcerative colitis) completed questionnaires.
      Multivariate analysis showed that a higher IBDKNOW score than the median was
      associated with hospitalization history (odds ratio [OR], 2.625; p = 0.003), high
      education level (OR, 2.498; p = 0.012), and information acquired from patient
      organization (OR, 3.305, p = 0.035). Conclusions: The IBD-KNOW demonstrated
      excellent test characteristics. Hospitalization history, education level, and
      information acquired from patient organization play an important role in correct
      IBD-related knowledge.

PMID- 29172401
TI  - Management of carbapenem-resistant Acinetobacter baumannii epidemic in an
      intensive care unit using multifaceted intervention strategy.
AB  - BACKGROUND/AIMS: We evaluated the effects of a multifaceted intervention for
      controlling a carbapenem-resistant Acinetobacter baumannii (CRAB) epidemic in an
      intensive care unit (ICU) with no restrictions on carbapenem use. METHODS: This
      study was conducted in a medical ICU between April 2012 and June 2016. The
      baseline infection control programs included surveillance cultures, contact
      precautions, and environmental cleaning. However, increases in the detection of
      CRAB isolates beginning in May 2013 led to the implementation of a new protocol,
      consisting of universal glove and gown use with daily chlorhexidine bathing for
      all patients in combination with baseline programs. The efficacy of the
      intervention was subjected to interrupted time series (ITS) analysis. RESULTS:
      The multifaceted intervention led to a decrease in the incidence of CRAB from
      17.65 to 0.89 cases per 1,000 patient-days, during the study period (p < 0.001).
      ITS analysis revealed a significant change in the trend of CRAB incidence (
      0.413, p < 0.001). Over this same period, mean monthly use of carbapenems
      increased from 143.54 +/- 95.73 to 204.95 +/- 78.43 doses per 1,000 patient-days
      (p = 0.018). CONCLUSION: Our multifaceted intervention reduced the incidence of
      CRAB acquisition in an ICU where carbapenem use was not restricted.

PMID- 29172402
TI  - Olmesartan is not associated with the risk of enteropathy: a Korean nationwide
      observational cohort study.
AB  - Background/Aims: Olmesartan, a widely used angiotensin II receptor blocker (ARB),
      has been linked to sprue-like enteropathy. No cases of olmesartan-associated
      enteropathy have been reported in Northeast Asia. We investigated the
      associations between olmesartan and other ARBs and the incidence of enteropathy
      in Korea. Methods: Our retrospective cohort study used data from the Korean
      National Health Insurance Service to identify 108,559 patients (58,186 females)
      who were initiated on angiotensin converting enzyme inhibitors (ACEis),
      olmesartan, or other ARBs between January 2005 and December 2012. The incidences
      of enteropathy were compared among drug groups. Changes in body weight were
      compared after propensity score matching of patients in the ACEis and olmesartan
      groups. Results: Among 108,559 patients, 31 patients were diagnosed with
      enteropathy. The incidences were 0.73, 0.24, and 0.37 per 1,000 persons, in the
      ACEis, olmesartan, and other ARBs groups, respectively. Adjusted rate ratios for
      enteropathy were: olmesartan, 0.33 (95% confidential interval [CI], 0.10 to 1.09;
      p = 0.070) and other ARBs, 0.34 (95% CI, 0.14 to 0.83; p = 0.017) compared to the
      ACEis group after adjustment for age, sex, income level, and various
      comorbidities. The post hoc analysis with matched cohorts revealed that the
      proportion of patients with significant weight loss did not differ between the
      ACEis and olmesartan groups. Conclusions: Olmesartan was not associated with
      intestinal malabsorption or significant body weight loss in the general Korean
      population. Additional large-scale prospective studies of the relationship
      between olmesartan and the incidence of enteropathy in the Asian population are
      needed.

PMID- 29172403
TI  - Circulating renalase predicts all-cause mortality and renal outcomes in patients
      with advanced chronic kidney disease.
AB  - Background/Aims: Patients with chronic kidney disease (CKD) have been found to
      show markedly increased rates of end-stage renal disease, major adverse
      cardiovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new
      biomarkers are required for the early detection of such clinical outcomes in
      patients with CKD. We aimed to determine whether the level of circulating
      renalase was associated with CKD progression, MACCEs, and all-cause mortality,
      using data from a prospective randomized controlled study, Kremezin STudy Against
      Renal disease progression in Korea (K-STAR; NCT 00860431). Methods: A
      retrospective analysis of the K-STAR data was performed including 383 patients
      with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating
      renalase levels and examined the effects of these levels on clinical outcomes.
      Results: The mean level of serum renalase was 75.8 +/- 34.8 MUg/mL. In the
      multivariable analysis, lower hemoglobin levels, higher serum creatinine levels,
      and diabetes mellitus were significantly associated with a higher renalase
      levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61
      MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137
      adverse renal outcomes occurred after a mean follow-up period of 27.8 months.
      Each 10- MUg/mL increase in serum renalase was associated with significantly
      greater hazards of all-cause mortality and adverse renal outcomes (hazard ratio
      [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level
      was not associated with the rate of MACCEs in patients with CKD. Conclusions: Our
      results indicated that circulating renalase might be a predictor of mortality and
      adverse renal outcomes in patients with CKD.

PMID- 29172404
TI  - Small RNA sequencing profiles of mir-181 and mir-221, the most relevant microRNAs
      in acute myeloid leukemia.
AB  - Background/Aims: To evaluate and select microRNAs relevant to acute myeloid
      leukemia (AML) pathogenesis, we analyzed differential microRNA expression by
      quantitative small RNA next-generation sequencing using duplicate marrow samples
      from individual AML patients. Methods: For this study, we obtained paired marrow
      samples at two different time points (initial diagnosis and first complete
      remission status) in patients with AML. Bone marrow microRNAs were profiled by
      next-generation small RNA sequencing. Quantification of microRNA expression was
      performed by counting aligned reads to microRNA genes. Results: Among 38 samples
      (32 paired samples from 16 AML patients and 6 normal marrow controls), 27 were
      eligible for sequencing. Small RNA sequencing showed that 12 microRNAs were
      selectively expressed at higher levels in AML patients than in normal controls.
      Among these 12 microRNAs, mir-181, mir-221, and mir-3154 were more highly
      expressed at initial AML diagnosis as compared to first complete remission.
      Significant correlations were found between higher expression levels of mir-221,
      mir-146, and mir-155 and higher marrow blast counts. Conclusions: Our results
      demonstrate that mir-221 and mir-181 are selectively enriched in AML marrow and
      reflect disease activity. mir-3154 is a novel microRNA that is relevant to AML
      but needs further validation.

PMID- 29172405
TI  - Risk of malignancy in patients with rheumatoid arthritis after anti-tumor
      necrosis factor therapy: results from Korean National Health Insurance claims
      data.
AB  - Background/Aims: Inhibition of tumor necrosis factor (TNF) is an effective
      treatment for rheumatoid arthritis (RA), but safety concerns about malignancy
      remain. The aim of this study was to evaluate cancer risk in RA patients treated
      with TNF inhibitors (TNFi), based on Korean Nationwide Health Insurance claims
      data. Methods: Patients with seropositive RA were selected from the health
      insurance database containing all citizens' medical information, based on both RA
      diagnosis codes and medications. Between 2010 and 2014, RA patients treated with
      conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and TNFi
      were enrolled and followed up. We compared the cancer incidence between patients
      treated with TNFi and csDMARDs using incidence rate ratios (IRRs) after
      adjustment for age, gender, and observational periods. Results: Of 45,423
      selected patients with seropositive RA, 2,337 were treated with TNFi and 43,086
      were treated with csDMARDs. The TNFi group was younger and was followed-up for a
      longer duration. During the observational period, 1,732 and 49 cases of cancer
      were detected in patients treated with csDMARDs and TNFi, respectively. Old age
      and male sex were associated with cancer occurrence. Adjusted IRRs for all
      cancers and common cancers demonstrated that cancer incidence did not differ
      significantly between the TNFi group and csDMARDs group (IRR = 0.913 for all
      cancers, p = 0.546). Conclusions: This study revealed that cancer incidence was
      similar in RA patients treated with TNFi and csDMARDs. Anti-TNF therapy may be a
      safe therapeutic option for RA treatment, in terms of malignancy.

PMID- 29172406
TI  - The impact of sarcopenia on health-related quality of life in elderly people:
      Korean National Health and Nutrition Examination Survey.
AB  - Background/Aims: The purpose of the study is to investigate the associations
      between sarcopenia and health-related quality of life in elderly men and women in
      Korea. Methods: In a cross-sectional study using data from 2008 to 2011 Korean
      National Health and Nutrition Examination Survey, 4,937 adults aged 60 years and
      older who underwent a dual-energy X-ray absorptiometry scan were included in the
      study. Sarcopenia is defined as an appendicular skeletal muscle index of two
      standard deviations or more below the mean for young, healthy reference
      populations. The health-related quality of life was measured using the EuroQol-5
      dimension questionnaire. Results: The overall prevalence of sarcopenia was 6.6%
      in these Korean people over the age of 60 years: 11.1% for men and 3.2% for
      women. Sarcopenic men tended to have lower income, lower physical activity, lower
      body mass index, and smaller waist circumference compared with nonsarcopenic men.
      Sarcopenic women tended to have higher body mass index and larger waist
      circumference compared with nonsarcopenic women. Sarcopenic men showed higher
      impairments in mobility, self-care, usual activities, and pain/discomfort
      compared with nonsarcopenic men. Women with sarcopenia also showed higher
      impairments in mobility, self-care, usual activities, and anxiety/depression
      compared with nonsarcopenic women. Sarcopenia showed an association with
      impairments in selfcare for men, and with impairments in self-care, usual
      activities, and anxiety/depression for women, after adjusting for other
      confounding factors. Conclusions: There is a significant association between
      sarcopenia and impaired health-related quality of life in this elderly Korean
      population, and these results differ between men and women.

PMID- 29172407
TI  - The impact of primary tumor location in patients with metastatic colorectal
      cancer: a Korean Cancer Study Group CO12-04 study.
AB  - Background/Aims: Colorectal cancer is associated with different anatomical,
      biological, and clinical characteristics. We determined the impact of the primary
      tumor location in patients with metastatic colorectal cancer (mCRC). Methods:
      Demographic data and clinical information were collected from 1,115 patients from
      the Republic of Korea, who presented with mCRC between January 2009 and December
      2011, using web-based electronic case report forms. Associations between the
      primary tumor location and the patient's clinical characteristics were assessed,
      and factors inf luencing overall survival were analyzed using Cox proportional
      hazards regression models. Results: Of the 1,115 patients recruited to the study,
      244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388
      (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in
      patients with left colon and rectal cancer (p = 0.005 and p = 0.006,
      respectively), while peritoneal and ovarian metastases occurred more frequently
      in patients with right and left colon cancer (p < 0.001 and p = 0.031,
      respectively). The median overall survival of patients with tumors originating in
      the right colon was significantly shorter than that of patients whose tumors had
      originated in the left colon or rectum (13.7 months [95% confidence interval
      (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95%
      CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of
      metastatic sites, and primary tumor location correlated with overall survival in
      the univariate and multivariate analyses. Conclusions: Primary tumor location
      influences the metastatic sites and prognosis of patients with mCRC.

PMID- 29172408
TI  - A novel neurofibromatosis type 1 (NF1) mutation in a patient with NF1 and
      pheochromocytoma.

PMID- 29172410
TI  - Contraception Update: Foreword.

PMID- 29172409
TI  - Prevalence of goiter and associated factors among schoolchildren in northeast
      Ethiopia.
AB  - OBJECTIVES: Goiter is a major public health problem, especially in developing
      countries such as Ethiopia. Hence, this study aimed to assess the prevalence and
      associated factors of goiter among children in Waghimra Zone, northeast Ethiopia.
      METHODS: A cross-sectional study was conducted from April 8 to 25, 2015 in
      northeast Ethiopia. A multistage sampling method was used to select 454
      schoolchildren. Data were collected using a pre-tested structured interviewer
      administered questionnaire. Children were examined for the presence or absence of
      goiter based on the criteria of the United Nations Children's Fund, International
      Council for the Control of Iodine Deficiency, and the World Health Organization.
      Salt samples from children's homes were tested for iodine levels using a rapid
      iodized salt test kit. Data were entered into EpiInfo version 7 and exported to
      SPSS version 20 for analysis. Bivariate and multivariate logistic regression
      models were fitted, and adjusted odds ratio (aOR) with 95% confidence interval
      (CI) were computed to determine the level of significance. RESULTS: The
      prevalence of goiter was 62.1% (95% CI, 57.5 to 66.5%). Being female (aOR, 3.09;
      95% CI, 1.57 to 6.08), having a family history of goiter (aOR, 5.18; 95% CI, 2.43
      to 11.03), and using non-iodized salt (aOR, 2.20; 95% CI, 1.12 to 4.38) were
      factors associated with goiter among schoolchildren. CONCLUSIONS: The prevalence
      of goiter was high. Being female and having a family history of goiter increased
      the risk of goiter in children, but using iodized salt was protective. Therefore,
      we recommend ensuring universal access to iodized salt and increasing the
      awareness of the community of the importance of iodized salt utilization.

PMID- 29172411
TI  - Contraception Update: Oral Contraception.
AB  - The oral contraceptive pill (OCP) is the most commonly used form of reversible
      contraception. The two types of OCPs are combination oral contraceptives (COCs),
      which contain estrogen and progesterone, and progestin-only pills (POPs). Both
      have failure rates of approximately 7.2% to 9% with typical use, and are safe for
      most patients. Because estrogen-containing contraceptives can increase the risk
      of venous thromboembolism, patients with conditions associated with a risk of
      cardiovascular events should not use COCs. Blood pressure level should be
      assessed before initiation of oral contraceptives. Noncontraceptive benefits of
      oral contraceptives include reduced risk of ovarian and endometrial cancers, more
      favorable bleeding patterns, and improvement in menstruation-related symptoms
      such as acne, migraine headaches, and premenstrual dysphoric disorder. OCPs can
      be initiated any time the physician can be reasonably certain that the patient is
      not pregnant. Extended cycle regimens may be preferred by some patients. After
      assessing need, physicians should present all methods that can be used safely
      using a tiered effectiveness approach. High-quality contraceptive counseling
      includes working collaboratively with patients to find the most effective and
      acceptable method for them and helping to identify factors that may assist in or
      hinder their ability to use the method correctly over time.

PMID- 29172412
TI  - Contraception Update: Intrauterine Devices.
AB  - Copper-containing and hormonal intrauterine devices (IUD) are long-acting, highly
      effective contraceptive methods. They can be used safely by nulliparous patients,
      adolescents, patients with history of ectopic pregnancy, and patients with risk
      factors for sexually transmitted infections or a history of pelvic inflammatory
      disease (PID). These devices can be placed safely immediately postpartum and
      postabortion and should be inserted when physicians can be reasonably certain
      that the woman is not pregnant. If a woman with an IUD is shown to be pregnant,
      the device should be removed if strings are visible. Bleeding and cramping after
      insertion can be managed with nonsteroidal anti-inflammatory drugs. Perforation
      is rare, but may require surgical removal of the device. If a woman with an IUD
      is diagnosed with PID, the device can be left in place and antibiotic treatment
      initiated.

PMID- 29172413
TI  - Contraception Update: Progestin-Only Implants and Injections.
AB  - Progestin-only contraception is a popular method of birth control in the United
      States and worldwide. Progestin-only implants and injections allow patients
      access to long-term contraception with simple options for reversal or removal.
      The implant is one of the most effective forms of contraception and there are few
      contraindications. Manufacturer-led training is required to become certified in
      insertion and removal. The most common adverse effect of the implant is a change
      in menstrual bleeding patterns. Little evidence has shown weight gain or
      decreased bone mineral density with use. The depot medroxyprogesterone acetate
      (DMPA) injection is used widely and is effective. Adverse effects that may limit
      use include changes in bleeding patterns and bone mineral density loss, which is
      reversible after discontinuation. The risk of weight gain with DMPA is greatest
      in obese adolescents and black patients. There is no significantly increased risk
      of cancer with either method. Both are safe for use in the postpartum period,
      during breastfeeding, and immediately after abortion.

PMID- 29172414
TI  - Contraception Update: Sterilization.
AB  - Female sterilization procedures include postpartum partial salpingectomy via
      cesarean or minilaparotomy incision, interval laparoscopic procedures, or
      hysteroscopic placement of microinserts. Rates of failure and serious
      complications are low and comparable among the various methods. A hysteroscopic
      procedure requires a 3-month confirmatory hysterosalpingogram before it is
      considered effective for contraception. Hysteroscopic sterilization has been
      shown to be associated with a higher reoperation rate than laparoscopic
      procedures. For male sterilization, vasectomy is a noninvasive and highly
      effective method. Vasectomy is an outpatient procedure performed under local
      anesthesia. The procedure requires confirmation of azoospermia with a semen
      analysis 8 to 16 weeks after the procedure. Patients who are considering
      sterilization should be counseled about all the available options and the
      permanent nature of such procedures.

PMID- 29172415
TI  - Photoresponsive and Magnetoresponsive Graphene Oxide Microcapsules Fabricated by
      Droplet Microfluidics.
AB  - Fluid compartmentalization by microencapsulation is important in scenarios where
      protection or controlled release of encapsulated species, or isolation of
      chemical transformations is the central concern. Realizing responsive
      encapsulation systems by incorporating functional nanomaterials is of particular
      interest. We report here on the development of graphene oxide microcapsules
      enabled by a single-step microfluidic process. Interfacial reaction of epoxide
      bearing graphene oxide sheets and an amine-functionalized macromolecular silicone
      fluid creates a chemically cross-linked film with micronscale thickness at the
      surface of water-in-oil droplets generated by microfluidic devices. The resulting
      microcapsules are monodisperse, mechanically resilient, and shape-tunable
      constructs. Ferrite nanoparticles are incorporated via the aqueous phase and
      enable microcapsule positioning by a magnetic field. We exploit the photothermal
      response of graphene oxide to realize microcapsules with photoresponsive release
      characteristics and show that the microcapsule permeability is significantly
      enhanced by near-IR illumination. The dual magnetic and photoresponsive
      characteristics, combined with the use of a single-step process employing
      biocompatible fluids, represent highly compelling aspects for practical
      applications.

PMID- 29172416
TI  - 808 nm Light-Triggered Thermometer-Heater Upconverting Platform Based on Nd3+
      Sensitized Yolk-Shell GdOF@SiO2.
AB  - The realization of real-time and accurate temperature reading at subcutaneous
      level during the photothermal therapy (PTT) could maximally avoid the collateral
      damages induced by overheating effects, which remains a formidable challenge for
      biomedical applications. Herein, 808 nm light-driven yolk-shell
      GdOF:Nd3+/Yb3+/Er3+@SiO2 microcapsules were developed with thermal-sensing and
      heating bifunctions. Under 808 nm excitation, sensitive thermometry was
      implemented by monitoring thermoresponsive emission from 2H11/2/4S3/2 levels of
      Er3+; meanwhile, the addition of Nd3+ with rich metastable intermediate levels
      and the yolk-shell configuration with large specific surface area triggered
      efficient light-to-heat conversion via enhanced nonradiative channels. The
      potentiality of dual-functional samples for controlled subcutaneous photothermal
      treatment was validated through ex vivo experiments, and the antibacterial
      activity against Escherichia coli was also elaborately evaluated. Results open a
      general avenue for designing and developing upconverting platforms with sensitive
      thermal-sensing and efficient heating bifunctions, which makes a significant step
      toward the achievement of real-time controlled PTT.

PMID- 29172417
TI  - Versatile Fabrication Approach of Conductive Hydrogels via Copolymerization with
      Vinyl Monomers.
AB  - Functionalized poly(ethylene dioxythiophene) (f-PEDOT) was copolymerized with two
      vinyl monomers of different hydrophilicity, acrylic acid and hydroxyethyl
      methacrylate, to produce electroconductive hydrogels with a range of physical and
      electronic properties. These hydrogels not only possessed tailored physical
      properties, such as swelling ratios and mechanical properties, but also displayed
      electroactivity dependent on the chemical composition of the network. Raman
      spectroscopy indicated that the functional PEDOT in the hydrogels is in an
      oxidized form, most likely accounting for the good electrochemical response of
      the hydrogels observed in physiological buffer. In vitro cell studies showed that
      cardiac cells respond differently when seeded on hydrogel substrates with
      different compositions. This study presents a facile approach for the fabrication
      of electroconductive hydrogels with a range of properties, paving the way for
      scaffolds that can meet the requirements of different electroresponsive tissues.

PMID- 29172418
TI  - Continuous Nanoparticle Assembly by a Modulated Photo-Induced Microbubble for
      Fabrication of Micrometric Conductive Patterns.
AB  - The laser-induced microbubble technique (LIMBT) has recently been developed for
      micro-patterning of various materials. In this method, a laser beam is focused on
      a dispersion of nanoparticles leading to the formation of a microbubble due to
      laser heating. Convection currents around the microbubble carry nanoparticles so
      that they become pinned to the bubble/substrate interface. The major limitation
      of this technique is that for most materials, a noncontinuous deposition is
      formed. We show that continuous patterns can be formed by preventing the
      microbubble from being pinned to the deposited material. This is done by
      modulating the laser so that the construction and destruction of the microbubble
      are controlled. When the method is applied to a dispersion of Ag nanoparticles,
      continuous electrically conductive lines are formed. Furthermore, the line width
      is narrower than that achieved by the standard nonmodulated LIMBT. This approach
      can be applied to the direct-write fabrication of micron-size conductive patterns
      in electronic devices without the use of photolithography.

PMID- 29172419
TI  - Enhanced Electrochemical Performance by Strongly Anchoring Highly Crystalline
      Polyaniline on Multiwalled Carbon Nanotubes.
AB  - Highly crystalline polyaniline (PANI) was strongly anchored on a multiwalled
      carbon nanotube (MWNT) surface, slowly grown from a controlled isothermal
      crystallization method utilizing pi-pi interactions. The crystalline PANI
      particles are approximately 10-38 nm thick, and the space between them varies
      from near 0 to 55 nm as reaction conditions vary. The highly crystalline
      nanohybrid (CNH) showed electrochemical performance enhancement compared with
      that of neat MWNTs, PANI, and the reference hybrid synthesized from chemical
      polymerization. The specific capacitance (SC) of CNHs was 726 F g-1 coupled with
      an excellent rate capability. Moreover, the strong combination between PANI and
      MWNTs as well as the crystalline structure in PANI improved the bulk
      conductivity, the interfacial charge transportation, and the cycling stability of
      the CNHs. The SC value of the CNHs remained almost unchanged upon 1000 charge
      discharge cycles, followed by just a slight decline of 2.6% after 10 000 cycle
      tests. X-ray diffraction data shows the SC decline mainly resulted from the
      structural variation of crystalline PANI. Furthermore, the resulting CNHs showed
      significant electrocatalytic behavior toward H2O2 and exhibited a low detection
      limit of 4.4 MUM due to the enhanced electron transportation between MWNTs and
      PANI. The reported method opens a gateway to design high-performance MWNT/PANI
      hybrids for use in electrochemical sensors, fuel cells, and energy-storage
      related devices.

PMID- 29172420
TI  - Constructing Nanostructured Donor/Acceptor Bulk Heterojunctions via Interfacial
      Templates for Efficient Organic Photovoltaics.
AB  - We demonstrate that a poly(3,4-ethylenedioxythiophene):poly(styrene
      sulfonate)/diindenoperylene (PEDOT:PSS/DIP) interfacial bilayer could serve as a
      structural template to enable the morphological control of bulk heterojunctions
      (BHJs) by co-evaporation of tetraphenyldibenzoperiflanthene:fullerene (DBP:C60),
      which greatly improves the device performances. Especially, we show that isolated
      crystalline domains of C60 can be well-controlled at the nanoscale during the co
      evaporation. Photoluminescence spectra indicate the realization of DIP/DBP
      cascade energy architecture, which significantly facilitates both the energy
      transfer and photocurrent generation. In addition, with bias-dependent external
      quantum efficiency analysis, we reveal that such a cascade energy device
      architecture greatly suppresses the energy recombination in both carrier and
      exciton transfer, resulting in a high open-circuit voltage and a high fill
      factor. By carefully optimizing the interfacial and BHJ layers, we achieved a
      high-performance organic photovoltaic cell with a power conversion efficiency of
      5.0 +/- 0.3%.

PMID- 29172421
TI  - Biomimetic Domain-Active Electrospun Scaffolds Facilitating Bone Regeneration
      Synergistically with Antibacterial Efficacy for Bone Defects.
AB  - To improve bone regeneration in oral microenvironment, we generated a novel
      biodegradable, antibacterial, and osteoconductive electrospun PLGA/PCL membrane
      as an ideal osteogenic scaffold. The novel three-layer membranes were structured
      with serial layers of electrospun chlorhexidine-doped-PLGA/PCL (PPC), PLGA/PCL
      (PP), and beta-tricalcium phosphate-doped-PLGA/PCL (PPbeta). To characterize
      osteoconductive properties of these membranes, MC3T3-E1 (MC) cultures were seeded
      onto the membranes for 14 days for evaluation of cell proliferation, morphology
      and gene/protein expression. In addition, MC cells were cultured onto different
      surfaces of the three-layer membranes, PPC layer facing MC cells (PPbeta-PP-PPC)
      and PPbeta layer facing MC cells (PPC-PP-PPbeta) to evaluate surface-material
      effects. Membrane properties and structures were evaluated. Antibacterial
      properties against Streptococcus mutans and Staphylococcus aureus were
      determined. Scanning electron microscope demonstrated smaller interfiber spaces
      of PPC and PPbeta-PP-PPC compared to PPbeta, PPC-PP-PPbeta, and PP. PPC and
      PPbeta-PP-PPC exhibited hydrophilic property. The three-layer membranes (PPC-PP
      PPbeta and PPbeta-PP-PPC) demonstrated significantly higher Young's modulus
      (94.99 +/- 4.03 MPa and 92.88 +/- 4.03 MPa) compared to PP (48.76 +/- 18.15 MPa)
      or PPC (7.92 +/- 3.97 MPa) (p < 0.05). No significant difference of cell
      proliferation was found among any groups at any time point (p > 0.05). Higher
      expression of integrins were detected at 12 h of cultures on PPC-PP-PPbeta
      compared to the controls. Promoted osteoconductive effects of PPC-PP-PPbeta were
      revealed by alkaline phosphatase assays and Western blot compared with the
      controls at 7 and 14 days. PPC, PPC-PP-PPbeta and PPbeta-PP-PPC exhibited a
      significantly wider antibacterial zone against the tested bacteria compared to PP
      and PPbeta (p < 0.05). These results suggested that the three-layer electrospun
      membranes demonstrated superior properties: higher strength, better cell
      adhesion, and promoted osteoconductive properties compared to single-layer
      membrane: however, antibacterial properties were exhibited in three-layer
      electrospun membranes and chlorhexidine-doped single-layer membrane. We concluded
      that the novel three-layer membranes could be used as a biocompatible scaffold
      for intraoral bone regeneration due to its enhanced osteoconductive activity and
      antibacterial effect.

PMID- 29172422
TI  - Deep Ultraviolet Copper(I) Thiocyanate (CuSCN) Photodetectors Based on Coplanar
      Nanogap Electrodes Fabricated via Adhesion Lithography.
AB  - Adhesion lithography (a-Lith) is a versatile fabrication technique used to
      produce asymmetric coplanar electrodes separated by a <15 nm nanogap. Here, we
      use a-Lith to fabricate deep ultraviolet (DUV) photodetectors by combining
      coplanar asymmetric nanogap electrode architectures (Au/Al) with solution
      processable wide-band-gap (3.5-3.9 eV) p-type semiconductor copper(I) thiocyanate
      (CuSCN). Because of the device's unique architecture, the detectors exhibit high
      responsivity (~79 A W-1) and photosensitivity (~720) when illuminated with a DUV
      range (lambdapeak = 280 nm) light-emitting diode at 220 MUW cm-2. Interestingly,
      the photosensitivity of the photodetectors remains fairly high (~7) even at
      illuminating intensities down to 0.2 MUW cm-2. The scalability of the a-Lith
      process combined with the unique properties of CuSCN paves the way to new forms
      of inexpensive, yet high-performance, photodetectors that can be manufactured on
      arbitrary substrate materials including plastic.

PMID- 29172423
TI  - Composition-Graded MoWSx Hybrids with Tailored Catalytic Activity by Bipolar
      Electrochemistry.
AB  - Among transition metal dichalcogenide (TMD)-based composites, TMD/graphene
      related material and bichalcogen TMD composites have been widely studied for
      application toward energy production via the hydrogen evolution reaction (HER).
      However, scarcely any literature explored the possibility of bimetallic TMD
      hybrids as HER electrocatalysts. The use of harmful chemicals and harsh
      preparation conditions in conventional syntheses also detracts from the objective
      of sustainable energy production. Herein, we present the conservational
      alternative synthesis of MoWSx via one-step bipolar electrochemical deposition.
      Through bipolar electrochemistry, the simultaneous fabrication of composition
      graded MoWSx hybrids, i.e., sulfur-deficient MoxW(1-x)S2 and MoxW(1-x)S3
      (MoWSx/BPEcathodic and MoWSx/BPEanodic, respectively) under cathodic and anodic
      overpotentials, was achieved. The best-performing MoWSx/BPEcathodic and
      MoWSx/BPEanodic materials exhibited Tafel slopes of 45.7 and 50.5 mV dec-1,
      together with corresponding HER overpotentials of 315 and 278 mV at -10 mA cm-2.
      The remarkable HER activities of the composite materials were attributed to their
      small particle sizes, as well as the near-unity value of their surface Mo/W
      ratios, which resulted in increased exposed HER-active sites and differing active
      sites for the concurrent adsorption of protons and desorption of hydrogen gas.
      The excellent electrocatalytic performances achieved via the novel methodology
      adopted here encourage the empowerment of electrochemical deposition as the
      foremost fabrication approach toward functional electrocatalysts for sustainable
      energy generation.

PMID- 29172424
TI  - Solution-Processed Plasmonic-Dielectric Sunlight-Collecting Nanofilms for Solar
      Thermoelectric Application.
AB  - It is important but remains a challenge to develop solution-processed plasmonic
      solar thermoelectricity films on various substrates, without strictly considering
      hierarchical plasmonic-dielectric-metal structures, to harvest a wide range of
      visible to near-infrared sunlight. We simply fabricate plasmonic silica
      metastructure sunlight-collecting nanofilms on highly reflective Cu and Si
      surfaces by introducing spin coating (with an Ag and silica colloidal mixture, a
      spin coater, and a heating plate) and low-temperature annealing (in an oven at
      200  degrees C for 1 h) processes. The approximately 250 nm thick metastructure
      consists of a top 60 nm thick silica layer as an antireflective film and a bottom
      190 nm thick Ag nanoparticle-silica hybrid film as a sunlight harvester. The
      metastructure film reduces the reflectivity of Cu (>90%) and Si (25-35%) to less
      than 5% at visible to near-infrared frequencies. The metastructure film on the Cu
      sheet has an absorptance of 0.95 and a thermal emittance of 0.06, ideal for high
      performance sunlight absorbers. The solar thermoelectric powers of the film
      coated Cu and Si are 15.4 and 4.7 times those of the uncoated Cu and Si
      substrates, respectively. The metastructure film on Cu exhibited a similar or
      slightly higher performance than that of a top-class vapor-deposited
      commercialized absorber film on Cu, demonstrating the robustness of the present
      method.

PMID- 29172425
TI  - High-Performance Green Light-Emitting Diodes Based on MAPbBr3-Polymer Composite
      Films Prepared by Gas-Assisted Crystallization.
AB  - The morphology of perovskite films has a significant impact on luminous
      characteristics of perovskite light-emitting diodes (PeLEDs). To obtain a highly
      uniform methylammonium lead tribromide (MAPbBr3) film, a gas-assisted
      crystallization method is introduced with a mixed solution of MAPbBr3 precursor
      and polymer matrix. The ultrafast evaporation of the solvent causes a high degree
      of supersaturation which expedites the generation of a large number of nuclei to
      form a MAPbBr3-polymer composite film with full surface coverage and nano-sized
      grains. The addition of the polymer matrix significantly affects the optical
      properties and morphology of MAPbBr3 films. The PeLED made of the MAPbBr3-polymer
      composite film exhibits an outstanding device performance of a maximum luminance
      of 6800 cd.m-2 and a maximum current efficiency of 1.12 cd.A-1. Furthermore, 1
      cm2 area pixel of PeLED displays full coverage of a strong green
      electroluminescence, implying that the high-quality perovskite film can be useful
      for large-area applications in perovskite-based optoelectronic devices.

PMID- 29172426
TI  - Diblock Copolymer PF-b-PDMAEMA as Effective Cathode Interfacial Material in
      Polymer Solar Cells.
AB  - An alcohol-soluble diblock copolymer poly[2,7-(9,9-dihexylfluorene)]15-block
      poly[2-(dimethylamino)ethyl methacrylate]75 (denoted as PF15-b-PDMAEMA75) was
      employed as the cathode interfacial layer (CIL) in p-i-n polymer solar cells
      (PSCs). PF15-b-PDMAEMA75 contains a conjugated rigid block and a nonconjugated
      flexible block grafted with polar amino groups, and it can effectively lower the
      work function of the Al cathode and decrease the series resistance of the
      devices. When applied as the CIL in PSCs based on poly[[4,8-bis[(2
      ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2
      ethylhexy)carbonyl]thieno[3,4-b]thiophenediyl]]:[6,6]-phenyl C71 butyric acid
      methyl ester, the champion power conversion efficiency of 8.80% was achieved,
      which is slightly higher than that of the PSCs using the well-known poly[(9,9
      bis(3'-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] as
      CIL under our experimental conditions, and much better than that of PSCs using Ca
      as CIL. The improvement of the performance is mainly attributed to the enhanced
      open-circuit voltage and fill factor. To the best of our knowledge, this is the
      first time a diblock copolymer has been used as a CIL in PSCs, and this study may
      provide a novel avenue for the design and synthesis of interfacial materials for
      high-performance PSCs.

PMID- 29172427
TI  - Long-Term Effect of Steam Exposure on CO2 Capture Performance of Amine-Grafted
      Silica.
AB  - This study investigates the hydrothermal stability of triamine-grafted CO2
      adsorbent based on a commercial-grade silica (CARiACT, P10). Grafting was
      conducted in dry and wet conditions at 85  degrees C. At optimum grafting
      conditions using 0.2 cm3 water and 1.5 cm3 aminosilane per gram of silica, the
      highest CO2 uptake of 1.93 mmol/g at 50  degrees C was obtained. This material
      was exposed to steam at 120  degrees C for up to 360 h. It was observed that
      increasing the duration of steam exposure from 3 to 24 h reduced adsorption
      uptake at 25  degrees C by 56%. However, the CO2 uptake reduction was much less
      severe at higher adsorption temperatures, reaching 21% at 50  degrees C and only
      4% at 75  degrees C. Conducting steam treatment for 360 h reduced adsorption
      uptake at 25, 50, and 75  degrees C by 83, 61, and 26%, respectively. For this
      extreme steaming experiment, the decrease in CO2 uptake at all adsorption
      temperatures was attributed to the reduction of the sorbent average pore width,
      increasing diffusional mass transfer resistance. The results revealed that steam
      exposure did not reduce the amine loading or deactivate the amine groups;
      however, increasing exposure time decreased the average pore width, until partial
      collapse of material structure. Nevertheless, the large average pore width (21
      nm) of the P10 silica led to higher hydrothermal stability of the amine-grafted
      sorbent compared to those with ordered pore structure supports, such as SBA-15
      silica.

PMID- 29172428
TI  - Uniform Surface Modification of Li2ZnTi3O8 by Liquated Na2MoO4 To Boost
      Electrochemical Performance.
AB  - Poor ionic and electronic conductivities are the key issues to affect the
      electrochemical performance of Li2ZnTi3O8 (LZTO). In view of the water
      solubility, low melting point, good electrical conductivity, and wettability to
      LZTO, Na2MoO4 (NMO) was first selected to modify LZTO via simply mixing LZTO in
      NMO water solution followed by calcining the dried mixture at 750  degrees C for
      5 h. The electrochemical performance of LZTO could be enhanced by adjusting the
      content of NMO, and the modified LZTO with 2 wt % NMO exhibited the most
      excellent rate capabilities (achieving lithiation capacities of 225.1, 207.2,
      187.1, and 161.3 mAh g-1 at 200, 400, 800, and 1600 mA g-1, respectively) as well
      as outstanding long-term cycling stability (delivering a lithiation capacity of
      229.0 mAh g-1 for 400 cycles at 500 mA g-1). Structure and composition
      characterizations together with electrochemical impedance spectra analysis
      demonstrate that the molten NMO at the sintering temperature of 750  degrees C is
      beneficial to diffuse into the LZTO lattices near the surface of LZTO particles
      to yield uniform modification layer, simultaneously ameliorating the electronic
      and ionic conductivities of LZTO, and thus is responsible for the enhanced
      electrochemical performance of LZTO. First-principles calculations further verify
      the substitution of Mo6+ for Zn2+ to realize doping in LZTO. The work provides a
      new route for designing uniform surface modification at low temperature, and the
      modification by NMO could be extended to other electrode materials to enhance the
      electrochemical performance.

PMID- 29172429
TI  - Dendritic Ternary Alloy Nanocrystals for Enhanced Electrocatalytic Oxidation
      Reactions.
AB  - Engineering the morphology and composition of multimetallic nanocrystals composed
      of noble and 3d transition metals has been of great interest due to its high
      potential to the development of high-performance catalytic materials for energy
      and sustainability. In the present work, we developed a facile aqueous approach
      for the formation of homogeneous ternary alloy nanocrystals with a dendritic
      shape, Pt-Pd-Cu nanodendrites, of which synthesis is hard to be achieved because
      of synthetic difficulties. Proper choice of stabilizer and fine control over the
      amount of stabilizer and reductant allowed the successful formation of Pt-Pd-Cu
      nanodendrites with controlled sizes and compositions. The prepared ternary alloy
      nanodendrites exhibited considerably improved electrocatalytic performance toward
      methanol and ethanol oxidation reactions compared to their binary alloy
      counterparts and commercial Pt and Pd catalysts, as well as to previously
      reported Pt- and Pd-based nanocatalysts because of synergism between their
      morphological and compositional characteristics. We anticipate that the present
      approach will be helpful to develop efficient electrocatalysis systems for
      practical applications.

PMID- 29172430
TI  - Ascorbic Acid Assisted High Performance Liquid Chromatography Mass Spectrometry
      Differentiation of Isomeric C-Chloro- and N-Chloro-Tyrosyl Peptides in Water.
AB  - We report a new method of ascorbic acid assisted high performance liquid
      chromatography (HPLC) with high resolution tandem mass spectrometry (HRMS/MS) for
      the differentiation of isomeric N-chloro (N-Cl) from phenol ring C-chloro (C-Cl)
      peptides produced during chlorination of water. Using the specific reductive
      nature of ascorbic acid, we successfully identified the N-Cl isomers and C-Cl
      isomer, overcoming the difficulty that, due to lack of standards, these isomers
      cannot be separated by HPLC-HRMS. Using the new approach, we identified 36 new
      chlorinated products including mono-, di-, tri-, and tetra-Cl-tyrosyl dipeptides
      in the reaction mixture based on retention time, accurate mass, 35Cl/37Cl
      isotopic pattern, and characteristic MS/MS fragments. The method was further
      applied to investigate competitive reactions when mixed tyrosyl dipeptides were
      chlorinated. Tyrosyl histidine was the most reactive tyrosyl dipeptide in the
      mixture. The chlorinated products formed are identical when the dipeptides are
      chlorinated separately or as a mixture. The formation conditions and stability of
      the chlorinated products were also examined. With increasing chlorine dose, the
      number of chlorine substituents on the tyrosyl dipeptides increased from products
      with one/two to three/four Cl atoms. Most of the chlorinated products are stable
      for up to 9 days. By chlorination of tyrosyl dipeptides spiked into raw water, we
      projected that chlorinated tyrosyl dipeptides can form during treatment of raw
      water containing tyrosyl dipeptides even at low MUg/L levels. This new method can
      be utilized for the discovery of a wide range of chlorinated peptide DBPs and the
      study of their formation and occurrence in water.

PMID- 29172431
TI  - A Hierarchically Modified Graphite Cathode with Au Nanoislands, Cysteamine, and
      Au Nanocolloids for Increased Electricity-Assisted Production of Isobutanol by
      Engineered Shewanella oneidensis MR-1.
AB  - It is necessary to understand the surface structural effects of electrodes on the
      bioalcohol productivity of Shewanella oneidensis MR-1, but this research area has
      not been deeply explored. Here, we report that the electricity-assisted
      isobutanol productivity of Shewanella oneidensis MR-1::pJL23 can be enhanced by
      sequentially modifying a graphite felt (GF) surface with Au nanoislands (Au),
      cysteamine (NH2), and Au nanoparticles (Au NPs). After bacteria were incubated
      for 50 h with the unmodified GF under various electrode potentials (vs Ag/AgCl),
      the bacterial isobutanol concentrations increased from 2.9 +/- 1 mg/L under no
      electricity supply to a maximum of 5.9 +/- 1 mg/L at -0.6 V. At this optimum
      electrode potential, the concentrations continued increasing to 9.1 +/- 1, 14 +/-
      2, and 27 +/- 2 mg/L when the GF electrodes were modified with Au, NH2-Au, and Au
      NP-NH2-Au, respectively. We further studied how each surface structure affected
      the bacterial adsorptions, current profiles, and biofilms' electrochemical
      performances. In particular, these modifications induced the adsorption of
      elongated bacteria, with the amount dependent on the electrode structure. In the
      presence of electric supply, the amount of elongated bacteria further increased.
      We also found that the NH2-Au-GF and Au NP-NH2-Au-GF electrodes themselves could
      increase the concentrations to 11 +/- 0.3 and 12 +/- 2 mg/L, respectively, upon
      the bacterial incubation without electricity. Among the electrodes tested, the
      contribution of electricity to the bacterial isobutanol production was the
      greatest with the Au NP-NH2-Au-GF electrode. After 96 h of incubation, the
      concentration increased to 72 +/- 2 mg/L, which was 4.7 and 3.7 times the
      previously reported values obtained without and with electricity, respectively.

PMID- 29172432
TI  - Hybridizing Carbon Nitride Colloids with a Shell of Water-Soluble Conjugated
      Polymers for Tunable Full-Color Emission and Synergistic Cell Imaging.
AB  - We present the preparation of a new multicolor emission system constructed from
      two complementary conjugated materials that are highly photoluminescent, that is,
      phenyl-modified carbon nitride (PhCN) colloids as the core and water-soluble
      conjugated polymers (WSCPs) adsorbed as the shell. The fluorescence bands of the
      PhCN and WSCPs effectively complement each other and the overall emission can be
      simply adjusted to fully cover the visible light spectrum with white light
      emission also accessible. Photophysical insights imply that the interactions
      between PhCN and WSCPs preserve the binary system from emission distortion and
      degradation, which is essential to delicately tune the overall fluorescence
      bands. Notably, the continuously tunable emission color is achieved under single
      wavelength excitation (365 nm). This hybrid shows a synergistic permeation
      performance in cell imaging, that is, PhCN nanoparticles help the WSCP to enter
      the cells and therefore multicolor cellular imaging achieved.

PMID- 29172433
TI  - Atom-Thick Interlayer Made of CVD-Grown Graphene Film on Separator for Advanced
      Lithium-Sulfur Batteries.
AB  - Lithium-sulfur batteries are widely seen as a promising next-generation energy
      storage system owing to their ultrahigh energy density. Although extensive
      research efforts have tackled poor cycling performance and self-discharge,
      battery stability has been improved at the expense of energy density. We have
      developed an interlayer consisting of two-layer chemical vapor deposition (CVD)
      grown graphene supported by a conventional polypropylene (PP) separator. Unlike
      interlayers made of discrete nano-/microstructures that increase the thickness
      and weight of the separator, the CVD-graphene is an intact film with an area of 5
      * 60 cm2 and has a thickness of ~0.6 nm and areal density of ~0.15 MUg cm-2,
      which are negligible to those of the PP separator. The CVD-graphene on PP
      separator is the thinnest and lightest interlayer to date and is able to suppress
      the shuttling of polysulfides and enhance the utilization of sulfur, leading to
      concurrently improved specific capacity, rate capability, and cycle stability and
      suppressed self-discharge when assembled with cathodes consisting of different
      sulfur/carbon composites and electrolytes either with or without LiNO3 additive.

PMID- 29172434
TI  - Challenges in the Development of a Thiol-Based Broad-Spectrum Inhibitor for
      Metallo-beta-Lactamases.
AB  - Pathogens, expressing metallo-beta-lactamases (MBLs), become resistant against
      most beta-lactam antibiotics. Besides the dragging search for new antibiotics,
      development of MBL inhibitors would be an alternative weapon against resistant
      bacterial pathogens. Inhibition of resistance enzymes could restore the
      antibacterial activity of beta-lactams. Various approaches to MBL inhibitors are
      described; among others, the promising motif of a zinc coordinating thiol moiety
      is very popular. Nevertheless, since the first report of a thiol-based MBL
      inhibitor (thiomandelic acid) in 2001, no steps in development of thiol based MBL
      inhibitors were reported that go beyond clinical isolate testing. In this study,
      we report on the synthesis and biochemical characterization of thiol-based MBL
      inhibitors and highlight the challenges behind the development of thiol-based
      compounds, which exhibit good in vitro activity toward a broad spectrum of MBLs,
      selectivity against human off-targets, and reasonable activity against clinical
      isolates.

PMID- 29172435
TI  - The Evolution of Chemical High-Throughput Experimentation To Address Challenging
      Problems in Pharmaceutical Synthesis.
AB  - The structural complexity of pharmaceuticals presents a significant challenge to
      modern catalysis. Many published methods that work well on simple substrates
      often fail when attempts are made to apply them to complex drug intermediates.
      The use of high-throughput experimentation (HTE) techniques offers a means to
      overcome this fundamental challenge by facilitating the rational exploration of
      large arrays of catalysts and reaction conditions in a time- and material
      efficient manner. Initial forays into the use of HTE in our laboratories for
      solving chemistry problems centered around screening of chiral precious-metal
      catalysts for homogeneous asymmetric hydrogenation. The success of these early
      efforts in developing efficient catalytic steps for late-stage development
      programs motivated the desire to increase the scope of this approach to encompass
      other high-value catalytic chemistries. Doing so, however, required significant
      advances in reactor and workflow design and automation to enable the effective
      assembly and agitation of arrays of heterogeneous reaction mixtures and retention
      of volatile solvents under a wide range of temperatures. Associated innovations
      in high-throughput analytical chemistry techniques greatly increased the
      efficiency and reliability of these methods. These evolved HTE techniques have
      been utilized extensively to develop highly innovative catalysis solutions to the
      most challenging problems in large-scale pharmaceutical synthesis. Starting with
      Pd- and Cu-catalyzed cross-coupling chemistry, subsequent efforts expanded to
      other valuable modern synthetic transformations such as chiral phase-transfer
      catalysis, photoredox catalysis, and C-H functionalization. As our experience and
      confidence in HTE techniques matured, we envisioned their application beyond
      problems in process chemistry to address the needs of medicinal chemists. Here
      the problem of reaction generality is felt most acutely, and HTE approaches
      should prove broadly enabling. However, the quantities of both time and starting
      materials available for chemistry troubleshooting in this space generally are
      severely limited. Adapting to these needs led us to invest in smaller predefined
      arrays of transformation-specific screening "kits" and push the boundaries of
      miniaturization in chemistry screening, culminating in the development of
      "nanoscale" reaction screening carried out in 1536-well plates. Grappling with
      the problem of generality also inspired the exploration of cheminformatics-driven
      HTE approaches such as the Chemistry Informer Libraries. These next-generation
      HTE methods promise to empower chemists to run orders of magnitude more
      experiments and enable "big data" informatics approaches to reaction design and
      troubleshooting. With these advances, HTE is poised to revolutionize how chemists
      across both industry and academia discover new synthetic methods, develop them
      into tools of broad utility, and apply them to problems of practical
      significance.

PMID- 29172436
TI  - Transparent and Flexible Surface-Enhanced Raman Scattering (SERS) Sensors Based
      on Gold Nanostar Arrays Embedded in Silicon Rubber Film.
AB  - Integration of surface-enhanced Raman scattering (SERS) sensors onto transparent
      and flexible substrates enables lightweight and deformable SERS sensors which can
      be wrapped or swabbed on various nonplanar surfaces for the efficient collection
      and detection of analytes on various surfaces. However, the development of
      transparent and flexible SERS substrates with high sensitivity is still
      challenging. Here, we demonstrate a transparent and flexible SERS substrate with
      high sensitivity based on a polydimethylsiloxane (PDMS) film embedded with gold
      nanostar (GNS) assemblies. The flexible SERS substrates enable conformal coverage
      on arbitrary surfaces, and the optical transparency allows light interaction with
      the underlying contact surface, thereby providing highly sensitive detection of
      analytes adsorbed on arbitrary metallic and dielectric surfaces which otherwise
      do not provide any noticeable Raman signals of analytes. In particular, when the
      flexible SERS substrates are covered onto metallic surfaces, the SERS enhancement
      is greatly improved because of the additional plasmon couplings between GNS and
      metal film. We achieve the detection capability of a trace amount of benzenethiol
      (10-8 M) and enormous SERS enhancement factor (~1.9 * 108) for flexible SERS
      substrates on Ag film. In addition, because of the embedded structure of GNS
      monolayers within the PDMS film, SERS sensors maintain the high sensitivity even
      after mechanical deformations of stretching, bending, and torsion for 100 cycles.
      The transparent and flexible SERS substrates introduced in this study are
      applicable to various SERS sensing applications on nonplanar surfaces, which are
      not achievable for hard SERS substrates.

PMID- 29172437
TI  - Use of Hupresin To Capture Red Blood Cell Acetylcholinesterase for Detection of
      Soman Exposure.
AB  - Toxicity from acute exposure to nerve agents and organophosphorus toxicants is
      due to irreversible inhibition of acetylcholinesterase (AChE) in the nervous
      system. AChE in red blood cells is a surrogate for AChE in the nervous system.
      Previously we developed an immunopurification method to enrich red blood cell
      AChE (RBC AChE) as a biomarker of exposure. The goal of the present work was to
      provide an alternative RBC AChE enrichment strategy, by binding RBC AChE to
      Hupresin affinity gel. AChE was solubilized from frozen RBC by addition of 1%
      Triton X-100. Insoluble debris was removed by centrifugation. The red, but not
      viscous, RBC AChE solution was loaded on a Hupresin affinity column. Hemoglobin
      and other proteins were washed off with 3 M NaCl, while retaining AChE bound to
      Hupresin. Denatured AChE was eluted with 1% trifluoroacetic acid. The same
      protocol was used for 20 mL of RBC AChE inhibited with a soman model compound.
      The acid denatured protein was digested with pepsin and analyzed by liquid
      chromatography tandem mass spectrometry on a 6600 Triple-TOF mass spectrometer. A
      targeted method identified the aged soman adduct on serine 203 in peptide
      FGESAGAAS. It was concluded that Hupresin can be used to enrich soman-inhibited
      AChE solubilized from 8 mL of frozen human erythrocytes, yielding a quantity
      sufficient for detecting soman exposure.

PMID- 29172438
TI  - 0D/2D Z-Scheme Heterojunctions of Bismuth Tantalate Quantum Dots/Ultrathin g-C3N4
      Nanosheets for Highly Efficient Visible Light Photocatalytic Degradation of
      Antibiotics.
AB  - Constructing 0D/2D Z-scheme photocatalysts is a great promising path to improve
      photocatalytic activity by  efficiently enhancing charge separation. Herein, we
      fabricated a visible-light-responsive Bi3TaO7 quantum dots (QDs)/g-C3N4
      nanosheets (NSs) 0D/2D Z-scheme composite via a facile ultrasound method, and
      Bi3TaO7 QDs could be interspersed on the surface of g-C3N4 NSs uniformly.
      Furthermore, the strong interaction between Bi3TaO7 QDs and g-C3N4 NSs disturbed
      the CN heterocycles by forming C?O bonds between C atoms of the N-(C)3 group and
      O atoms of the Ta-O bond. The optimum composite with 20 wt % g-C3N4 NSs showed
      the superior photocatalytic activity for degradation of ciprofloxacin (CIP) over
      the composites prepared by mechanical mixing and solid-state methods, the
      photocatalytic efficiency of which were 4 and 12.2 times higher than those of
      bare Bi3TaO7 and g-C3N4. Photoluminescence (PL), time-resolved transient PL decay
      spectra, and photocurrent together verify that the photogenerated hole-electron
      pairs in this 0D/2D Z-scheme composite have been effectively separated. The
      enhanced photocatalytic activity of as-synthesized photocatalysts could be
      attributed to the synergistic effect of efficient Z-scheme charge separation,
      highly dispersed 0D Bi3TaO7 nanocrystals, coordinating sites of 2D g-C3N4 NSs and
      the strong coupling between them. This study might pave the way toward designing
      novel visible-light-induced 0D/2D photocatalyst systems for highly efficient
      degradation of antibiotics.

PMID- 29172439
TI  - Altered CREB Binding to Activity-Dependent Genes in Serine Racemase Deficient
      Mice, a Mouse Model of Schizophrenia.
AB  - cAMP-response-element-binding protein (CREB) is a transcription factor
      ubiquitously expressed in the brain that regulates neuroplasticity by modulating
      gene expression. The influx of calcium through N-methyl-d-aspartate receptors
      (NMDARs) is a well-defined mechanism that leads to the increased expression of
      CREB-dependent genes, including brain derived neurotrophic factor (BDNF),
      microRNA-132, and activity-regulated cytoskeleton-associated protein (Arc). These
      molecules are implicated in the pathophysiology of schizophrenia. We previously
      demonstrated that serine racemase knockout (SR-/-) mice, which exhibit NMDAR
      hypofunction due to a lack of the forebrain NMDAR co-agonist d-serine, also have
      reduced expression of CREB-dependent genes in the hippocampus. Using chromatin
      immunoprecipitation, we show here that, in SR-/- mice, there is less CREB bound
      to the promoter regions of BDNF, microRNA-132, and Arc. These data suggest that
      NMDAR hypofunction in SR-/- mice leads to reduced CREB binding on known activity
      dependent genes, in turn contributing to their reduced expression.

PMID- 29172441
TI  - Method of Polonium Source Preparation Using Tellurium Microprecipitation for
      Alpha Spectrometry.
AB  - A thin-layer source for the counting of polonium isotopes by alpha spectrometry
      can be rapidly prepared using microprecipitation with tellurium. Polonium was
      first coprecipitated with the reduction of tellurium by stannous chloride,
      followed by microfiltration onto a membrane filter for counting. This
      microprecipitation method is faster, cheaper, and more convenient than the
      traditional spontaneous deposition method, with an excellent Po recovery (>90%)
      under optimal conditions. The influences of several experimental parameters,
      including Te(IV) quantity, reaction time, and HCl molarity, were examined to
      determine the optimal conditions for Te microprecipitation. The decontamination
      factors of potential interferences from various radionuclides (Ra, Th, U, Pu, Am)
      for the counting of long-lived polonium isotopes (208Po, 209Po, and 210Po) were
      also evaluated, and the results confirmed a good selectivity on polonium by this
      microprecipitation method. Due to its strong resistance to high acidity up to 12
      M HCl, the method would be particularly suitable for rapid determination of 210Po
      in acid leaching solution of solid samples.

PMID- 29172440
TI  - Mitochondrial GSH Systems in CA1 Pyramidal Cells and Astrocytes React Differently
      during Oxygen-Glucose Deprivation and Reperfusion.
AB  - Pyramidal cells and astrocytes have differential susceptibility to oxygen-glucose
      deprivation and reperfusion (OGD-RP). It is known that excessive reactive oxygen
      species (ROS) in mitochondria initiates cell death, while glutathione (GSH) is
      one of the major defenses against ROS. Although it is known that astrocytes
      contain a higher concentration of GSH than neurons, and that astrocytes can
      provide neurons with GSH, we are unaware of a detailed and quantitative
      examination of the dynamic changes in the mitochondrial GSH system in the two
      cell types during OGD-RP. Here, we determined mitochondrial membrane potential
      and the degrees of oxidation of the mitochondrially targeted roGFP-based sensors
      for hydrogen peroxide (OxDP) and GSH (OxDG). We also developed a method to
      estimate the mitochondrial GSH (mGSH) concentration in single cells in the CA1
      region of organotypic hippocampal slice cultures at several time-points during
      OGD-RP. We find that mitochondrial membrane potential drops in pyramidal cells
      during OGD while it is relatively stable in astrocytes. In both types of cell,
      the mitochondrial membrane potential decreases during RP. During OGD-RP,
      mitochondrial peroxide levels are the same. Astrocytic mGSH is more than four
      times higher than pyramidal cell mGSH (3.2 vs 0.7 mM). Astrocytic mGSH is drained
      from mitochondria during OGD, whereas in pyramidal cells it remains fairly
      constant. OxDGSH prior to and during OGD is lower (less oxidized) in pyramidal
      cells than in astrocytes, but the two nearly converge during RP. The larger
      changes of redox status in the GSH system in pyramidal cells than astrocytes is
      an upstream sign of the higher mortality of the pyramidal cells after facing an
      insult. The pattern of [mGSH] changes in the two cell types could be recognized
      as another mechanism by which astrocytes protect neurons from transient, extreme
      conditions.

PMID- 29172442
TI  - Interface Engineering of Mn-Doped ZnSe-Based Core/Shell Nanowires for Tunable
      Host-Dopant Coupling.
AB  - Transition metal ion doped one-dimensional (1-D) nanocrystals (NCs) have
      advantages of larger absorption cross sections and polarized absorption and
      emissions in comparison to 0-D NCs. However, direct synthesis of doped 1-D
      nanorods (NRs) or nanowires (NWs) has proven challenging. In this study, we
      report the synthesis of 1-D Mn-doped ZnSe NWs using a colloidal hot-injection
      method and shell passivation for core/shell NWs with tunable optical properties.
      Experimental results show optical properties of the NWs are controlled by the
      composition and thickness of the shell lattice. It was found that both the host
      Mn energy transfer and Mn-Mn coupling are strongly dependent on the type of alloy
      at the interface of doped core/shell NWs. For Mn-doped type I ZnSe/ZnS core/shell
      NWs, the ZnS shell passivation can enhance florescence quantum yield with little
      effect on the location of the incorporated Mn dopant due to the identical
      cationic Zn2+ site available for Mn dopants throughout the core/shell NWs.
      However, for Mn-doped quasi type II ZnSe/CdS NWs and ZnSe/CdS/ZnS core/shell NWs,
      the cation alloying (Zn1-xCdxS(e)) can lead to metal dopant migration from the
      core to the alloyed interface and tunable host-dopant energy transfer
      efficiencies and Mn-Mn coupling. As a result, a tunable dual-band emission can be
      achieved for the doped NWs with the cation-alloyed interface. The interfacial
      alloying mediated energy transfer and Mn-Mn coupling provides a method to control
      the optical properties of the doped 1-D core/shell NWs.

PMID- 29172443
TI  - Membrane Crossing and Membranotropic Activity of Cell-Penetrating Peptides:
      Dangerous Liaisons?
AB  - Living organisms have to maintain a stable balance in molecules and ions in the
      changing environment in which they are living, a process known as homeostasis. At
      the level of cells, the plasma membrane has a major role in homeostasis, since
      this hydrophobic film prevents passive diffusion of large and hydrophilic
      molecules between the extracellular and intracellular milieu. Living organisms
      have evolved with highly sophisticated transport systems to control exchanges
      across this barrier: import of nutrients and fuel essential for their survival;
      recognition of chemical or physical messengers allowing information interchanges
      with surrounding cells. Besides specialized proteins, endocytosis mechanisms at
      the level of the lipid bilayer can transport molecules from the outside across
      the cell membrane, in an energy-dependent manner. The cell membrane is highly
      heterogeneous in its molecular composition (tens of different lipids, proteins,
      polysaccharides, and combinations of these) and dynamic with bending,
      deformation, and elastic properties that depend on the local composition of
      membrane domains. Many viruses, microorganisms, and toxins exploit the plasma
      membrane to enter into cells. Chemists develop strategies to target the plasma
      membrane with molecules capable of circumventing this hydrophobic barrier, in
      particular to transport and deliver nonpermeable drugs in cells for
      biotechnological or pharmaceutical purposes. Drug delivery systems are numerous
      and include lipid-, sugar-, protein-, and peptide-based delivery systems, since
      these biomolecules generally have good biocompatibility, biodegradability,
      environmental sustainability, cost effectiveness, and availability. Among those,
      cell-penetrating peptides (CPPs), reported for the first time in the early 1990s,
      are attracting major interest not only as potential drug delivery systems but
      also at the level of fundamental research. It was indeed demonstrated very early
      that these peptides, which generally correspond to highly cationic sequences, can
      still cross the cell membrane at 4  degrees C, a temperature at which all active
      transport and endocytosis pathways are totally inhibited. Therefore, how these
      charged hydrophilic peptides cross the hydrophobic membrane barrier is of utmost
      interest as a pure basic and physicochemical question. In this Account, we focus
      on cationic cell-penetrating peptides (CPPs) and the way they cross cell
      membranes. We summarize the history of this field that emerged around 20 years
      ago. CPPs were indeed first identified as protein-transduction domains from the
      human immunodeficiency virus (HIV) TAT protein and the Antennapedia homeoprotein,
      a transcription factor from Drosophila. We highlight our contribution to the
      elucidation of CPP internalization pathways, in particular translocation, which
      implies perturbation and reorganization of the lipid bilayer, and endocytosis
      depending on sulfated glycosaminoglycans. We show a particular role of Trp
      (indole side chain) and Arg (guanidinium side chain), which are essential amino
      acids for CPP internalization. Interactions with the cell-surface are not only
      Coulombic; H-bonds and hydrophobic interactions contribute also significantly to
      CPP entry. The capacity of CPPs to cross cell membrane is not related to their
      strength of membrane binding. Finally, we present optimized methods based on mass
      spectrometry and fluorescence spectroscopy that allow unequivocal quantification
      of CPPs inside cells or bound to the outer leaflet of the membrane, and discuss
      some limitations of the technique of flow cytometry that we have recently
      highlighted.

PMID- 29172444
TI  - Metal-Free Cataluminescence Gas Sensor for Hydrogen Sulfide Based on Its
      Catalytic Oxidation on Silicon Carbide Nanocages.
AB  - Cataluminescence- (CTL-) based sensors are among the most attractive and
      effective tools for gas sensing, owing to their efficient selectivity, high
      sensitivity, and rapidity. As the sensing materials of CTL-based sensors, metal
      based catalysts easily bring about high costs and environmental pollution of
      heavy metals. More importantly, the long-term stability of metal-based catalysts
      is usually rather poor. Metal-free catalysts have unique advantages such as
      environmental friendliness, low costs, and long-term stability, making them
      promising materials for CTL-based sensors. Herein, we report the fabrication of a
      CTL sensor based on a metal-free catalyst. F-doped cage-like SiC was synthesized
      by wet chemical etching. The as-prepared products showed a rapid, stable, highly
      selective, and sensitive cataluminescent response to H2S. The stability of the
      sensor was demonstrated to be fairly good for at least 15 days. After CTL tests,
      F-doped cage-like SiC retained its original morphology, structure, and chemical
      composition. In addition, to the best of our knowledge, this is the first report
      of a metal-free CTL sensor. Metal-free catalysts are environmentally friendly and
      low in cost and exhibit long-term stability, which could open a new avenue of CTL
      sensing.

PMID- 29172445
TI  - Toward Theoretically Cycling-Stable Lithium-Sulfur Battery Using a Foldable and
      Compositionally Heterogeneous Cathode.
AB  - Rechargeable lithium-sulfur (Li-S) batteries have been expected for new
      generation electrical energy storages, which are attributed to their high
      theoretical energy density, cost effectiveness, and eco-friendliness. But Li-S
      batteries still have some problems for practical application, such as low sulfur
      utilization and dissatisfactory capacity retention. Herein, we designed and
      fabricated a foldable and compositionally heterogeneous three-dimensional sulfur
      cathode with integrated sandwich structure. The electrical conductivity of the
      cathode is facilitated by three different dimension carbons, in which short
      distance and long-distance pathways for electrons are provided by zero
      dimensional ketjen black (KB), one-dimensional activated carbon fiber (ACF) and
      two-dimensional graphene (G). The resultant three-dimensional sulfur cathode (T
      AKG/KB@S) with an areal sulfur loading of 2 mg cm-2 exhibits a high initial
      specific capacity, superior rate performance and a reversible discharge capacity
      of up to 726 mAh g-1 at 3.6 mA cm-2 with an inappreciable capacity fading rate of
      0.0044% per cycle after 500 cycles. Moreover, the cathode with a high areal
      sulfur loading of 8 mg cm-2 also delivers a reversible discharge capacity of 938
      mAh g-1 at 0.71 mA cm-2 with a capacity fading rate of 0.15% per cycle and a
      Coulombic efficiency of almost 100% after 50 cycles.

PMID- 29172446
TI  - A Compatible Sensitivity Enhancement Strategy for Electrochemiluminescence
      Immunosensors Based on the Biomimetic Melanin-Like Deposition.
AB  - In this work, a compatible strategy was demonstrated for the enhancement of
      detection sensitivity of sandwich-type electrochemiluminescence (ECL)
      immunosensors. The enhanced signal response was based on the combination of
      biomimetic melanin-like deposition with the effective ECL quenching ability of
      quinone-rich biopolymers. Gold nanoparticle-loaded horseradish peroxidase (HRP)
      was used as a catalytic label for the secondary antibodies. The intrinsic
      catalytic property of HRP toward hydrogen peroxide (H2O2) generates reactive
      oxygen species, which highly promote the autopolymerization of catecholamines.
      The resulting fast deposition of quinone-rich biopolymers approaching the
      luminophor-incorporated sensing platform achieves an obvious ECL quenching. A
      broad-spectrum tumor marker alpha fetoprotein (AFP) was selected as a model
      analyte to demonstrate the feasibility of the proposed strategy. Under optimal
      conditions, a very low detection limit of 0.056 pg mL-1 was obtained. Two orders
      of magnitude enhancement was achieved in contrast to the signal response without
      the step of catalytic biopolymer deposition. The combination of compatible HRP
      labeling with unique melanin-like deposition has potential as a universal
      strategy in other ECL bioassays.

PMID- 29172447
TI  - Change in the Crystallite Orientation of Poly(ethylene oxide)/Cellulose Nanofiber
      Composite Films.
AB  - The crystallite orientation and crystallographic domain structure of
      poly(ethylene oxide) (PEO) in cellulose nanofiber-incorporated (CNF-incorporated)
      PEO films developed for packaging materials were observed using wide-angle X-ray
      diffraction for different CNF filling ratios. When a CNF filling ratio of <10 wt
      % was used, the molecular chains in the PEO crystallite region were oriented in a
      direction perpendicular to the surface of the film; however, when the ratio was
      >50 wt %, the PEO molecular chains were oriented in a direction parallel to the
      surface of the film. The fiber axis of the CNFs became parallel to the surface of
      the PEO/CNF composite film when the filling ratio was >25 wt %. The change in the
      orientation of the PEO crystals occurred because increasing the amount of CNF in
      the composite films decreased the space in which the PEO could be crystallized.
      Furthermore, the hydrogen bonds between the PEO and the CNF may behave as
      crystallization nuclei for the PEO. Our results thus pave the way toward the
      development of packaging materials that are more impermeable to gases than the
      current materials.

PMID- 29172448
TI  - Oxidized Alginate-Based Hydrogels for Tissue Engineering Applications: A Review.
AB  - Oxidized alginate (OA)-based hydrogels have drawn considerable attention as
      biodegradable materials for tissue engineering applications. OA possesses a
      faster degradation rate and contains more reactive groups compared to native
      alginate. This review summarizes the research publications reporting the
      development of OA-based hydrogels for tissue engineering applications including
      bone, cartilage, blood vessel, cornea, and other soft tissues, highlighting OA
      key properties and processing approaches.

PMID- 29172449
TI  - EXOPLEXs: Chimeric Drug Delivery Platform from the Fusion of Cell-Derived
      Nanovesicles and Liposomes.
AB  - Cell-derived nanovesicles (CDNs) have been recently investigated as novel drug
      delivery systems (DDSs), due to the preservation of key features from the cell
      membrane of their precursor cells, which are responsible for an efficient
      cellular uptake by target cells. However, CDNs suffer from low drug loading
      efficiencies as well as challenges in functionalization compared to conventional
      DDS like liposomes. Here, we describe the first study proposing the fusion of
      CDNs with liposomes to form EXOPLEXs. We report the preservation of cell
      membranes from precursor cells similarly to CDNs, as well as high loading
      efficiencies of more than 65% with doxorubicin hydrochloride, a model
      chemotherapeutic drug. The doxorubicin-loaded EXOPLEXs (DOX-EXO) also
      demonstrated a higher in vitro cell killing effect than liposomes, while EXOPLEXs
      alone did not show any remarkable cytotoxicity. Taken together, these results
      illustrate the potential of EXOPLEXs as a novel DDS for targeted delivery of
      chemotherapeutics.

PMID- 29172450
TI  - Endogenous Alpha-Synuclein Protein Analysis from Human Brain Tissues Using Single
      Molecule Pull-Down Assay.
AB  - Alpha-synuclein (alpha-SYN) is a central molecule in Parkinson's disease
      pathogenesis. Despite several studies, the molecular nature of endogenous alpha
      SYN especially in human brain samples is still not well understood due to the
      lack of reliable methods and the limited amount of biospecimens. Here, we
      introduce alpha-SYN single-molecule pull-down (alpha-SYN SiMPull) assay combined
      with in vivo protein crosslinking to count individual alpha-SYN protein and
      assess its native oligomerization states from biological samples including human
      postmortem brains. This powerful single-molecule assay can be highly useful in
      diagnostic applications using various specimens for neurodegenerative diseases
      including Alzheimer's disease and Parkinson's disease.

PMID- 29172451
TI  - Core-Corona Magnetic Nanospheres Functionalized with Zwitterionic Polymer Ionic
      Liquid for Highly Selective Isolation of Glycoprotein.
AB  - A novel zwitterionic polymer ionic liquid functionalized magnetic nanospheres,
      shortly as Fe3O4@PCL-PILs, is synthesized by grafting ionic liquid VimCOOHBr onto
      polymer epsilon-caprolactone (PCL) modified magnetic nanospheres via
      esterification and surface-initiated free radical polymerization. This
      established synthesis strategy offers the obtained magnetic nanospheres with well
      defined core-corona structure, compact grafting layer, favorable zwitterionic and
      negative-charged surface, and high magnetic susceptibility. The as-prepared
      Fe3O4@PCL-PILs nanospheres exhibit typical "zwitterionic hydrophilic interaction
      liquid chromatography (ZIC-HILIC)" behaviors toward protein binding, and
      selectively adsorption of glycoprotein is achieved. The adsorption capacity of
      the magnetic nanospheres toward Immunoglobulin G is high up to 1136.4 mg g-1, and
      the captured Immunoglobulin G could be efficiently recovered by using 0.5% NH3
      H2O (v/v) as stripping reagent, providing a recovery of 80.5%. Fe3O4@PCL-PILs
      nanospheres are then employed as sorbent for the selective isolation of
      Immunoglobulin G from human whole blood, obtaining high-purity Immunoglobulin G
      as demonstrated by polyacrylamide gel electrophoresis assays.

PMID- 29172452
TI  - Adaption of a Solid-State Nanopore to Homogeneous DNA Organization Verification
      and Label-Free Molecular Analysis without Covalent Modification.
AB  - Recent advances have shown increasing designs of nucleic acid organizations via
      controlling the thermodynamics and kinetics of oligonucleotides. Nevertheless,
      deeper understanding and further applications of these DNA nanotechnologies are
      majorly hampered by the lack of effective analytical methodologies that are
      competent enough to investigate them. To deliver a potential solution, here we
      developed an innovative exploration that employed the emerging nanopore technique
      to characterize DNA organization at the single-molecule level and in completely
      homogeneous condition without covalent modification. With the help of counting
      and profiling the translocation-induced current drop of a DNA assembly structure
      passing through a conical glass nanopore (CGN), we have directly verified the
      formation of the individual double-helix concatemer generated from our model,
      hybridization chain reaction (HCR). Due to the ultrasensitivity of the nanopore
      technology, those concatemers that were difficult to observe on a conventional
      electrophoresis image were brought to light. The translocation duration time also
      provided the approximate length and folding information for the concatemers.
      These advantages were proven also applicable to structures with more
      sophisticated folding behaviors. Eventually, when coupling with an upstream
      reaction, CGN was further turned to a universal detector that was capable of even
      detecting other nucleic acid organization behaviors as well as targets that were
      unable to generate huge products. All of these results are expected to promote
      deeper study and applications of the nanopore technique in the field of nucleic
      acid nanotechnology.

PMID- 29172453
TI  - Sample Concentration of Charged Small Molecules and Peptides in Capillary
      Electrophoresis by Micelle to Cyclodextrin Stacking.
AB  - A stacking approach in capillary electrophoresis based on the reversal of the
      analytes' effective electrophoretic velocities at a dynamic stacking boundary
      formed between charged micelles (i.e., from long chain ionic surfactants) and
      neutral cyclodextrins (i.e., native alpha-, beta-, or gamma-cyclodextrin) is
      presented. The approach was demonstrated by the long injection of samples in a
      micellar solution followed by injection of a cyclodextrin solution zone, and then
      separation by co-electro-osmotic flow capillary zone electrophoresis. The
      reversal is caused by the formation of stable cyclodextrin-surfactant complexes
      at the boundary that significantly decreased the retention factor of the analytes
      in the presence of a micellar pseudostationary phase. The dynamic boundary was
      formed at the cyclodextrin zone as the micelles penetrated this zone. Under
      optimum conditions, the boundary disappears, and the stacking ends when all the
      micelles have electrophoretically migrated to the boundary. Cationic and anionic
      small molecules were enriched using oppositely charged micelles from sodium
      dodecyl sulfate and cetyltrimethylammonium bromide, respectively. There were 1-2
      orders of concentration magnitude improvement in analyte detection, which is
      expected in stacking with hydrodynamic injection. The improvements in the peak
      signals (height/corrected area) were up to 236/445 and 101/76 for the cationic
      and anionic analytes tested, respectively. Linearity (r2) and repeatability (%RSD
      of migration time, peak height, and corrected peak area) under the chosen
      stacking conditions (cations/anions) were >=0.998/>=0.995 and <=3.8%/<=5.7%,
      respectively. The stacking approach was also implemented in the direct analysis
      of peptides from trypsin digested bovine serum albumin.

PMID- 29172456
TI  - Ocrelizumab: A New Therapeutic Paradigm for Multiple SclerosisPublished as part
      of the Biochemistry series "Biochemistry to Bedside".

PMID- 29172455
TI  - Characterizing the Structure-Function Relationship of a Naturally Occurring RNA
      Thermometer.
AB  - A large number of bacteria have been found to govern virulence and heat shock
      responses using temperature-sensing RNAs known as RNA thermometers. A prime
      example is the agsA thermometer known to regulate the production of the AgsA heat
      shock protein in Salmonella enterica using a "fourU" structural motif. Using the
      SHAPE-Seq RNA structure-probing method in vivo and in vitro, we found that the
      regulator functions by a subtle shift in equilibrium RNA structure populations
      that leads to a partial melting of the helix containing the ribosome binding
      site. We also demonstrate that binding of the ribosome to the agsA mRNA causes
      changes to the thermometer structure that appear to facilitate thermometer helix
      unwinding. These results demonstrate how subtle RNA structural changes can govern
      gene expression and illuminate the function of an important bacterial regulatory
      motif.

PMID- 29172457
TI  - Characterizing Deformability and Electrical Impedance of Cancer Cells in a
      Microfluidic Device.
AB  - Mechanical properties of cells, reflective of various biochemical characteristics
      such as gene expression and cytoskeleton, are promising label-free biomarkers for
      studying and characterizing cells. Electrical properties of cells, dependent on
      the cellular structure and content, are also label-free indicators of cell states
      and phenotypes. In this work, we have developed a microfluidic device that is
      able to simultaneously characterize the mechanical and electrical properties of
      individual biological cells in a high-throughput manner (>1000 cells/min). The
      deformability of MCF-7 breast cancer cells was characterized based on the passage
      time required for an individual cell to pass through a constriction smaller than
      the cell size. The total passage time can be divided into two components: the
      entry time required for a cell to deform and enter a constriction, which is
      dominated by the deformability of cells, and the transit time required for the
      fully deformed cell to travel inside the constriction, which mainly relies on the
      surface friction between cells and the channel wall. The two time durations for
      individual cells to pass through the entry region and transit region have both
      been investigated. In addition, undeformed cells and fully deformed cells were
      simultaneously characterized via electrical impedance spectroscopy technique. The
      combination of mechanical and electrical properties serves as a unique set of
      intrinsic cellular biomarkers for single-cell analysis, providing better
      differentiation of cellular phenotypes, which are not easily discernible via
      single-marker analysis.

PMID- 29172458
TI  - Transiently Thermoresponsive Acetal Polymers for Safe and Effective
      Administration of Amphotericin B as a Vaccine Adjuvant.
AB  - The quest for new potent and safe adjuvants with which to skew and boost the
      immune response of vaccines against intracellular pathogens and cancer has led to
      the discovery of a series of small molecules that can activate Toll-like
      receptors (TLRs). Whereas many small molecule TLR agonists cope with a
      problematic safety profile, amphotericin B (AmpB), a Food and Drug Administration
      approved antifungal drug, has recently been discovered to possess TLR-triggering
      activity. However, its poor aqueous solubility and cytotoxicity at elevated
      concentrations currently hampers its development as a vaccine adjuvant. We
      present a new class of transiently thermoresponsive polymers that, in their
      native state, have a phase-transition temperature below room temperature but
      gradually transform into fully soluble polymers through acetal hydrolysis at
      endosomal pH values. RAFT polymerization afforded well-defined block copolymers
      that self-assemble into micellar nanoparticles and efficiently encapsulate AmpB.
      Importantly, nanoencapsulation strongly reduced the cytotoxic effect of AmpB but
      maintained its TLR-triggering capacity. Studies in mice showed that AmpB-loaded
      nanoparticles can adjuvant an RSV vaccine candidate with almost equal potency as
      a highly immunogenic oil-in-water benchmark adjuvant.

PMID- 29172461
TI  - Ionic Liquids from Biocompatibility and Electrochemical Aspects toward Applying
      in Biosensing Devices.
AB  - The introduction of a novel ionic environment, which is composed of a large,
      asymmetric organic cation and inorganic (or organic) anion that loosely fit
      together, is extending the properties and classical applications of
      chemical/biochemical and industrial performances. In this Feature, we discuss the
      recent uses of ionic liquids in enzyme activation and their combination with
      nanosized materials and electrode structures to enhance the sensing performance
      of biobased sensing devices.

PMID- 29172460
TI  - N-Phenyl-2-naphthylamine as a Novel MALDI Matrix for Analysis and in Situ Imaging
      of Small Molecules.
AB  - Due to its strong ultraviolet absorption, low background interference in the
      small molecular range, and salt tolerance capacity, N-phenyl-2-naphthylamine
      (PNA) was developed as a novel matrix in the present study for analysis and
      imaging of small molecules by matrix-assisted laser desorption/ionization mass
      spectrometry time-of-fight (MALDI-TOF MS). The newly developed matrix displayed
      good performance in analysis of a wide range of small-molecule metabolites
      including free fatty acids, amino acids, peptides, antioxidants, and
      phospholipids. In addition, PNA-assisted LDI MS imaging of small molecules in
      brain tissue of rats subjected to middle cerebral artery occlusion (MCAO)
      revealed unique distributions and changes of 89 small-molecule metabolites
      including amino acids, antioxidants, free fatty acids, phospholipids, and
      sphingolipids in brain tissue 24 h postsurgery. Fifty-nine of the altered
      metabolites were identified, and all the changed metabolites were subject to
      relative quantitation and statistical analysis. The newly developed matrix has
      great potential application in the field of biomedical research.

PMID- 29172459
TI  - Structural Characterization of Ferrous Ion Binding to Retinal Guanylate Cyclase
      Activator Protein 5 from Zebrafish Photoreceptors.
AB  - Sensory guanylate cyclases (zGCs) in zebrafish photoreceptors are regulated by a
      family of guanylate cyclase activator proteins (called GCAP1-7). GCAP5 contains
      two nonconserved cysteine residues (Cys15 and Cys17) that could in principle bind
      to biologically active transition state metal ions (Zn2+ and Fe2+). Here, we
      present nuclear magnetic resonance (NMR) and isothermal titration calorimetry
      (ITC) binding analyses that demonstrate the binding of one Fe2+ ion to two GCAP5
      molecules (in a 1:2 complex) with a dissociation constant in the nanomolar range.
      At least one other Fe2+ binds to GCAP5 with micromolar affinity that likely
      represents electrostatic Fe2+ binding to the EF-hand loops. The GCAP5 double
      mutant (C15A/C17A) lacks nanomolar binding to Fe2+, suggesting that Fe2+ at this
      site is ligated directly by thiolate groups of Cys15 and Cys17. Size exclusion
      chromatography analysis indicates that GCAP5 forms a dimer in the Fe2+-free and
      Fe2+-bound states. NMR structural analysis and molecular docking studies suggest
      that a single Fe2+ ion is chelated by thiol side chains from Cys15 and Cys17 in
      the GCAP5 dimer, forming an [Fe(SCys)4] complex like that observed previously in
      two-iron superoxide reductases. Binding of Fe2+ to GCAP5 weakens its ability to
      activate photoreceptor human GC-E by decreasing GC activity >10-fold. Our results
      indicate a strong Fe2+-induced inhibition of GC by GCAP5 and suggest that GCAP5
      may serve as a redox sensor in visual phototransduction.

PMID- 29172462
TI  - ADP-Ribosylation, a Multifaceted Posttranslational Modification Involved in the
      Control of Cell Physiology in Health and Disease.
AB  - Posttranslational modifications (PTMs) regulate protein functions and
      interactions. ADP-ribosylation is a PTM, in which ADP-ribosyltransferases use
      nicotinamide adenine dinucleotide (NAD+) to modify target proteins with ADP
      ribose. This modification can occur as mono- or poly-ADP-ribosylation. The latter
      involves the synthesis of long ADP-ribose chains that have specific properties
      due to the nature of the polymer. ADP-Ribosylation is reversed by hydrolases that
      cleave the glycosidic bonds either between ADP-ribose units or between the
      protein proximal ADP-ribose and a given amino acid side chain. Here we discuss
      the properties of the different enzymes associated with ADP-ribosylation and the
      consequences of this PTM on substrates. Furthermore, the different domains that
      interpret either mono- or poly-ADP-ribosylation and the implications for cellular
      processes are described.

PMID- 29172454
TI  - The Role of Electron Transfer Dissociation in Modern Proteomics.

PMID- 29172463
TI  - Filling in the Gaps between Nanozymes and Enzymes: Challenges and Opportunities.
AB  - Using nanomaterials to mimic the function of protein enzymes is an interesting
      idea. Many nanomaterials have a similar size as enzymes and they also possess
      catalytic activity. Over the past decade, a surge of nanozyme work has emerged,
      likely due to the advancement in the synthesis and characterization of inorganic
      nanoparticles. Many typical enzymatic reactions mimicking oxidases, peroxidases,
      laccases, superoxide dismutases, and catalases have been realized by simple metal
      oxide and metal nanoparticles. In addition, small inorganic catalysts have been
      loaded in nanoparticles to create another type of nanozyme. The applications of
      nanozymes in biosensor design, environmental remediation, and therapeutics have
      been demonstrated. In this Topical Review, we briefly summarize the current
      status of the field and then focus our attention on some important problems faced
      by the field. These topics include developing better nanozymes with higher
      activity, better substrate selectivity, and engineering enzyme-like active sites.
      For practical applications, reliable methods for bioconjugation of nanozymes with
      affinity ligands need to be achieved, but not at the cost of losing the activity
      of nanozymes. Finally, fundamental mechanistic studies are needed to rationally
      design nanozymes and to obtain key insights into a few model systems.

PMID- 29172464
TI  - Methylmercury Modulation in Amazon Rivers Linked to Basin Characteristics and
      Seasonal Flood-Pulse.
AB  - We investigated the impact of the seasonal inundation of wetlands on
      methylmercury (MeHg) concentration dynamics in the Amazon river system. We
      sampled 38 sites along the Solimoes/Amazon and Negro rivers and their tributaries
      during distinct phases of the annual flood-pulse. MeHg dynamics in both basins
      was contrasted to provide insight into the factors controlling export of MeHg to
      the Amazon system. The export of MeHg by rivers was substantially higher during
      high-water in both basins since elevated MeHg concentrations and discharge
      occurred during this time. MeHg concentration was positively correlated to
      %flooded area upstream of the sampling site in the Solimoes/Amazon Basin with the
      best correlation obtained using 100 km buffers instead of whole basin areas. The
      lower correlations obtained with the whole basin apparently reflected variable
      losses of MeHg exported from upstream wetlands due to demethylation, absorption,
      deposition, and degradation before reaching the sampling site. A similar
      correlation between %flooded area and MeHg concentrations was not observed in the
      Negro Basin probably due to the variable export of MeHg from poorly drained soils
      that are abundant in this basin but not consistently flooded.

PMID- 29172465
TI  - A New Step in the Treatment of Sickle Cell DiseasePublished as part of the
      Biochemistry series "Biochemistry to Bedside".

PMID- 29172466
TI  - An Unsymmetric Ligand Framework for Noncoupled Homo- and Heterobimetallic
      Complexes.
AB  - We introduce a new unsymmetric ligand, PDIpCy (PDI = pyridyldiimine; Cy =
      cyclam), that offers two distinct, noncoupled coordination sites. A series of
      homo- and heterobimetallic complexes, [Zn2(PDIpCy)(THF)(OTf)4] (1; THF =
      tetrahydrofuran and OTf = triflate), [Ni2(PDIpCy)(THF)(OTf)2](OTf)2 (2), and
      [NiZn(PDIpCy)(THF)(OTf)4] (3), are described. The one-electron-reduced compounds,
      [Zn2(PDIpCy)(OTF)3] (4), [Ni2(PDIpCy)(OTf)](OTf)2 (5), and [NiZn(PDIpCy)(OTf)3]
      (6), were isolated, and their electronic structures were characterized. The
      reduced compounds are charge-separated species, with electron storage at either
      the PDI ligand (4) or at the PDI-bound metal ion (5 and 6).

PMID- 29172467
TI  - The Promise of Self-Assembled 3D Supramolecular Coordination Complexes for
      Biomedical Applications.
AB  - In the supramolecular chemistry field, coordination-driven self-assembly has
      provided the basis for tremendous growth across many subdisciplines, spanning
      from fundamental investigations regarding the design and synthesis of new
      architectures to defining different practical applications. Within this
      framework, supramolecular coordination complexes (SCCs), defined as large
      chemical entities formed from smaller precursor building blocks of ionic metal
      nodes and organic multidentate ligands, resulting in intricate and well-defined
      supramolecular structures, hold great promise. Notably, interest in the
      construction of discrete 3D molecular architectures, such as those offered by
      SCCs, has experienced extraordinary progress because of their potential
      application as sensors, catalysts, probes, and containers and in basic host-guest
      chemistry. Despite numerous synthetic efforts and a number of inherent favorable
      properties, the field of 3D SCCs for biomedical applications is still in its
      infancy. This Viewpoint focuses on 3D SCCs, specifically metallacages and
      helicates, first briefly presenting the fundamentals in terms of the synthesis
      and characterization of their host-guest properties, followed by an overview of
      the possible biological applications with representative examples. Thus, emphasis
      will be given in particular to metallacages as drug delivery systems and to
      chiral helicates as DNA recognition domains. Overall, we will provide an update
      on the state-of-the-art literature and will define the challenges in this
      fascinating research area at the interface of different disciplines.

PMID- 29172468
TI  - Coordination of Hydrogen Peroxide with Late-Transition-Metal Sulfonamido
      Complexes.
AB  - Adducts of hydrogen peroxide and transition metals have been implicated as
      intermediates in biological and industrial processes but have only recently been
      observed. Therefore, knowledge of how hydrogen peroxide interacts with transition
      metals is extremely limited. Herein, we report the synthesis of H2O2 complexes of
      cobalt, nickel, and copper supported by sulfonamido ligands with second-sphere
      hydrogen bonding. Binding constant and decay kinetics are reported for four new
      M(H2O2) adducts, providing a foundation for future studies in H2O2 coordination
      and oxidation catalysis.

PMID- 29172469
TI  - Trackable Metallodrugs Combining Luminescent Re(I) and Bioactive Au(I) Fragments.
AB  - Hetero-bimetallic and -trimetallic complexes were synthesized by the combination
      of different metallic fragments, a luminescent Re(I) species, and a bioactive
      Au(I) derivative. A ditopic P,N-donor ligand (L) was used as linker between both
      metals, affording six new bipyridine (bipy) Re(I)/Au(I) hetero-metallic complexes
      of the type fac-[Re(bipy)(CO)3(LAuCl)]+ (4-6) and [(fac-[Re(bipy)(CO)3(L)])2Au]3+
      (7-9) after a thorough synthetic procedure. Their emission is associated with a
      triplet metal-to-ligand charge transfer (Re(dpi) -> bipy(pi*)) transition and red
      shifted in polar solvents with lifetimes in the range of nanoseconds and quantum
      yield values up to 12.5%. Cytotoxicity values in A549 cells of hetero-trimetallic
      species are almost twice that for the hetero-bimetallic (ca. 37 vs 69 MUM,
      respectively), being the L-Au fragment the source of the antiproliferative
      activity. Species 7 and 8 showed similar behavior by fluorescence microscopy,
      with a nonuniform cytoplasmatic distribution, a clear accumulation in single
      spots at the edge of the inner cell membrane as well as in areas within the
      nucleus. Preliminary studies suggest the DNA as one of the targets and passive
      diffusion as the entrance pathway.

PMID- 29172470
TI  - Simplifying Assays by Tableting Reagents.
AB  - Medical diagnostic assays provide exquisite sensitivity and precision in the
      diagnoses of patients. However, these technologies often require multiple steps,
      skilled technicians, and facilities to store heat-sensitive reagents. Here, we
      developed a high-throughput compression method to incorporate different assay
      components into color-coded tablets. With our technique, premeasured quantities
      of reagents can be encapsulated in compressed tablets. We show that tableting
      stabilizes heat-sensitive reagents and simplifies a broad range of assays,
      including isothermal nucleic acid amplification techniques, enzyme-based
      immunoassays, and microbead diagnostics. To test the clinical readiness of this
      tableting technology, we show the ability of tableted diagnostics for screening
      hepatitis B-positive patient samples. Our development simplifies complicated
      assays and the transportation of reagents and mitigates the need for
      refrigeration of reagents. This advances the use of complex assays in remote
      areas with limited infrastructure.

PMID- 29172471
TI  - Ratio of Methylmercury to Dissolved Organic Carbon in Water Explains
      Methylmercury Bioaccumulation Across a Latitudinal Gradient from North-Temperate
      to Arctic Lakes.
AB  - We investigated monomethylmercury (MMHg) bioaccumulation in lakes across a 30
      degrees  latitudinal gradient in eastern Canada to test the hypothesis that
      climate-related environmental conditions affect the sensitivity of Arctic lakes
      to atmospheric mercury contamination. Aquatic invertebrates (chironomid larvae,
      zooplankton) provided indicators of MMHg bioaccumulation near the base of benthic
      and planktonic food chains. In step with published data showing latitudinal
      declines in atmospheric mercury deposition in Canada, we observed lower total
      mercury concentrations in water and sediment of higher latitude lakes. Despite
      latitudinal declines of inorganic mercury exposure, MMHg bioaccumulation in
      aquatic invertebrates did not concomitantly decline. Arctic lakes with greater
      MMHg in aquatic invertebrates either had (1) higher water MMHg concentrations
      (reflecting ecosystem MMHg production) or (2) low water concentrations of MMHg,
      dissolved organic carbon (DOC), chlorophyll, and total nitrogen (reflecting lake
      sensitivity). The MMHg:DOC ratio of surface water was a strong predictor of lake
      sensitivity to mercury contamination. Bioaccumulation factors for biofilms and
      seston in Arctic lakes showed more efficient uptake of MMHg in low DOC systems.
      Environmental conditions associated with low biological production in Arctic
      lakes and their watersheds increased the sensitivity of lakes to MMHg.

PMID- 29172472
TI  - In Situ Subcellular Imaging of Copper and Zinc in Contaminated Oysters Revealed
      by Nanoscale Secondary Ion Mass Spectrometry.
AB  - Determining the in situ localization of trace elements at high lateral resolution
      levels in the biological system is very challenging, but critical for our
      understanding of metal sequestration and detoxification. Here, the cellular and
      subcellular distributions of Cu and Zn in contaminated oysters of Crassostrea
      hongkongensis were for the first time mapped using nanoscale secondary ion mass
      spectrometry (nanoSIMS). Three types of metal-containing cells were revealed in
      the gill and mantle of oysters, including Cu-specific hemocytes, Cu and Zn
      containing granular hemocytes, and Cu and Zn-containing calcium cells. Obvious
      intercellular distribution of Cu was found in the gill tissue, indicating the
      potential role of hemolymph in the transportation of Cu in oysters. The
      distribution of Cu showed a strong colocalization with sulfur and nitrogen in Cu
      specific hemocyte and intercellular hemolymph. In the Cu and Zn-containing
      granular hemocytes and calcium cells, the co-occurrence of Cu and Zn with
      phosphorus and calcium was also found. Different relationships of distributions
      between Cu/Zn and macronutrient elements (nitrogen, sulfur and phosphorus)
      implied the differential metal complexation in oysters. Interestingly,
      quantitative analysis of the ratios of 32S-/12C14N- and 31P-/12C14N- of metal
      deposited sites suggested the dynamic process of transfer of Cu and Zn from the
      metabolized protein pool to a more thermodynamically stable and detoxified form.

PMID- 29172473
TI  - Chemical Degradation of Polyacrylamide during Hydraulic Fracturing.
AB  - Polyacrylamide (PAM) based friction reducers are a primary ingredient of
      slickwater hydraulic fracturing fluids. Little is known regarding the fate of
      these polymers under downhole conditions, which could have important
      environmental impacts including decisions on strategies for reuse or treatment of
      flowback water. The objective of this study was to evaluate the chemical
      degradation of high molecular weight PAM, including the effects of shale, oxygen,
      temperature, pressure, and salinity. Data were obtained with a slickwater
      fracturing fluid exposed to both a shale sample collected from a Marcellus
      outcrop and to Marcellus core samples at high pressures/temperatures (HPT)
      simulating downhole conditions. Based on size exclusion chromatography analyses,
      the peak molecular weight of the PAM was reduced by 2 orders of magnitude, from
      roughly 10 MDa to 200 kDa under typical HPT fracturing conditions. The rate of
      degradation was independent of pressure and salinity but increased significantly
      at high temperatures and in the presence of oxygen dissolved in fracturing
      fluids. Results were consistent with a free radical chain scission mechanism,
      supported by measurements of sub-MUM hydroxyl radical concentrations. The shale
      sample adsorbed some PAM (~30%), but importantly it catalyzed the chemical
      degradation of PAM, likely due to dissolution of Fe2+ at low pH. These results
      provide the first evidence of radical-induced degradation of PAM under HPT
      hydraulic fracturing conditions without additional oxidative breaker.

PMID- 29172474
TI  - Relationship of Biodiversity with Heavy Metal Tolerance and Sorption Capacity: A
      Meta-Analysis Approach.
AB  - Microbial remediation of metals can alleviate the concerns of metal pollution in
      the environment. The microbial remediation, however, can be a complex process
      since microbial metal resistance and biodiversity can play a direct role in the
      bioremediation process. This study aims to understand the relationships among
      microbial metal resistance, biodiversity, and metal sorption capacity. Meta
      analyses based on 735 literature data points of minimum inhibitory concentrations
      (MIC) of Plantae, Bacteria, and Fungi exposed to As, Cd, Cr Cu, Ni, Pb, and Zn
      showed that metal resistance depends on the microbial Kingdom and the type of
      heavy metal and that consortia are significantly more resistant to heavy metals
      than pure cultures. A similar meta-analysis comparing 517 MIC values from
      different bacterial genera (Bacillus, Cupriavidus, Klebsiella, Ochrobactrum,
      Paenibacillus, Pseudomonas, and Ralstonia) confirmed that metal tolerance depends
      on the type of genus. Another meta-analysis with 195 studies showed that the
      maximum sorption capacity is influenced by microbial Kingdoms, the type of
      biosorbent (whether consortia or pure cultures), and the type of metal. This
      study also suggests that bioremediation using microbial consortia is a valid
      option to reduce environmental metal contaminations.

PMID- 29172475
TI  - Re(CO)3-Templated Synthesis of alpha-Amidinoazadi(benzopyrro)methenes.
AB  - alpha-Amidinoazadi(benzopyrro)methenes were synthesized using the Re(CO)3 unit as
      a templating agent. The products of these template reactions are six-coordinate
      rhenium complexes, with a facial arrangement of carbonyls, a noncoordinating
      anion, and a tridentate alpha-amidinoazadi(benzopyrro)methene ligand. The
      tridentate ligand shows the conversion of one diiminoisoindoline sp2 carbon to a
      sp3 carbon, which has been seen in the "helmet" and bicyclic phthalocyanines. The
      bidentate diiminoisoindoline fragment tilts out of the plane of coordination.
      Five examples of alpha-amidinoazadi(benzopyrro)methenes produced from these
      reactions using different nitrile solvents, including the nitrile activation of
      acetonitrile, propionitrile, butyronitrile, cyclohexanecarbonitrile, and
      benzonitrile.

PMID- 29172476
TI  - Correction to "Modular Attachment of Appended Boron Lewis Acids to a Ruthenium
      Pincer Catalyst: Metal-Ligand Cooperativity Enables Selective Alkyne
      Hydrogenation".

PMID- 29172477
TI  - Introducing NacNac-Like Bis(4,6-isopropylbenzoxazol-2-yl)methanide in s-Block
      Metal Coordination.
AB  - Within this work, the field of bulky methanides in metal coordination is exceeded
      by the synthesis of the versatile and promising bis(4,6-isopropylbenzoxazol-2
      yl)methane (7) ligand platform. As an enhancement in this class of ligands,
      isopropyl (iPr) substituents as steric-demanding groups have been successfully
      introduced in proximity to the coordination pocket, mimicking the shielding
      abilities of the ubiquitous NacNac ligand scaffold to improve the steric
      protection of a coordinated s-block metal cation. A percent buried volume (%
      Vbur) calculation as well as an electronic structure analysis shades light onto
      the shielding and electronic abilities of the ligand in comparison to other
      selected methanides and diketiminates. Upon deprotonation with a variety of
      different group 1 and 2 metalation agents, a row of novel s-block metal complexes
      of the parent deprotonated monoanionic ligand 7 was obtained and structurally, as
      well as spectroscopically, characterized. In particular, in this context, the
      alkali-metal precursor complexes [Li(THF)2{(4,6-iPr-NCOC6H2)2CH}] (8) and [K{MU
      (4,6-iPr-NCOC6H2)2CH}]infinity (9) as well as the alkaline-earth-metal compounds
      [MgCl(THF)2{(4,6-iPr-NCOC6H2)2CH}] (10) and [M(THF)n{(4,6-iPr-NCOC6H2)2CH}2] [M =
      Mg, n = 0 (11); M = Ca, n = 1 (12); M = Sr, n = 1 (13); M = Ba, n = 1 (14)] were
      successfully synthesized. Especially, the latter four exhibit interesting trends
      in the solid state as well as in solution within the metal series.

PMID- 29172478
TI  - Controlled Dimerization of Mn12 Single-Molecule Magnets.
AB  - Controlled dimerization of Mn12 single-molecule magnets (SMMs) was achieved via a
      synthetic route involving a competition between bridging and terminal ligands,
      namely, diols and alcohols. The reaction using a 1:1 ratio of the competing
      ligands resulted in the isolation of a new family of covalently linked dimers of
      Mn12 SMMs. This is the first step toward the controlled growth of SMM oligomeric
      arrays.

PMID- 29172479
TI  - Enamine/Dienamine and Bronsted Acid Catalysis: Elusive Intermediates, Reaction
      Mechanisms, and Stereoinduction Modes Based on in Situ NMR Spectroscopy and
      Computational Studies.
AB  - Over the years, the field of enantioselective organocatalysis has seen
      unparalleled growth in the development of novel synthetic applications with
      respect to mechanistic investigations. Reaction optimization appeared to be
      rather empirical than rational. This offset between synthetic development and
      mechanistic understanding was and is generally due to the difficulties in
      detecting reactive intermediates and the inability to experimentally evaluate
      transition states. Thus, the first key point for mechanistic studies is detecting
      elusive intermediates and characterizing them in terms of their structure,
      stability, formation pathways, and kinetic properties. The second key point is
      evaluating the importance of these intermediates and their properties in the
      transition state. In the past 7 years, our group has addressed the problems with
      detecting elusive intermediates in organocatalysis by means of NMR spectroscopy
      and eventually theoretical calculations. Two main activation modes were
      extensively investigated: secondary amine catalysis and, very recently, Bronsted
      acid catalysis. Using these examples, we discuss potential methods to stabilize
      intermediates via intermolecular interactions; to elucidate their structures,
      formation pathways and kinetics; to change the kinetics of the reactions; and to
      address their relevance in transition states. The elusive enamine in proline
      catalyzed aldol reactions is used as an example of the stabilization of
      intermediates via inter- and intramolecular interactions; the determination of
      kinetics on its formation pathway is discussed. Classical structural
      characterization of intermediates is described using prolinol and prolinol ether
      enamines and dienamines. The Z/E dilemma for the second double bond of the
      dienamines shows how the kinetics of a reaction can be changed to allow for the
      detection of reaction intermediates. We recently started to investigate substrate
      catalyst complexes in the field of Bronsted acid catalysis. These studies on
      imine/chiral phosphoric acid complexes show that an appropriate combination of
      highly developed NMR and theoretical methods can provide detailed insights into
      the complicated structures, exchange kinetics, and H-bonding properties of chiral
      ion pairs. Furthermore, the merging of these structural investigations and
      photoisomerization even allowed the active transition state combinations to be
      determined for the first time on the basis of experimental data only, which is
      the gold standard in mechanistic investigations and was previously thought to be
      exclusively the domain of theoretical calculations. Thus, this Account summarizes
      our recent mechanistic work in the field of organocatalysis and explains the
      potential methods for addressing the central questions in mechanistic studies:
      stabilization of intermediates, elucidation of structures and formation pathways,
      and addressing transition state combinations experimentally.

PMID- 29172480
TI  - Myricetin Reduces Toxic Level of CAG Repeats RNA in Huntington's Disease (HD) and
      Spino Cerebellar Ataxia (SCAs).
AB  - Huntington's disease (HD) is a neurodegenerative disorder that is caused by
      abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA
      contains expanded CAG repeats that translate into a mutant huntingtin protein.
      This expanded CAG repeat also causes mis-splicing of pre-mRNA due to
      sequestration of muscle blind like-1 splicing factor (MBNL1), and thus both of
      these elicit the pathogenesis of HD. Targeting the onset as well as progression
      of HD by small molecules could be a potent therapeutic approach. We have screened
      a set of small molecules to target this transcript and found Myricetin, a
      flavonoid, as a lead molecule that interacts with the CAG motif and thus prevents
      the translation of mutant huntingtin protein as well as sequestration of MBNL1.
      Here, we report the first solution structure of the complex formed between
      Myricetin and RNA containing the 5'CAG/3'GAC motif. Myricetin interacts with this
      RNA via base stacking at the AA mismatch. Moreover, Myricetin was also found
      reducing the proteo-toxicity generated due to the aggregation of polyglutamine,
      and further, its supplementation also improves neurobehavioral deficits in the HD
      mouse model. Our study provides the structural and mechanistic basis of Myricetin
      as an effective therapeutic candidate for HD and other polyQ related disorders.

PMID- 29172482
TI  - Amino Terminal Copper and Nickel Binding Motif Derivatives of Ovispirin-3 Display
      Increased Antimicrobial Activity via Lipid Oxidation.
AB  - Antimicrobial peptides are short peptides secreted by the innate immune system to
      protect the host from pathogens. We have investigated the influence of the amino
      terminal copper and nickel binding (ATCUN) motif on derivatives of ovispirin-3
      (OV-3), an alpha-helical peptide from the cathelicidin family, demonstrating an
      increased antimicrobial activity toward a broad range of bacteria, relative to OV
      3, with MICs as low as 1.3 +/- 0.6 MUM. Each peptide was able to bind DNA and RNA
      with micromolar affinity, but did not display nuclease activity in vivo. The
      ATCUN OV-3 derivatives also displayed an increased membrane leakage and lipid
      peroxidation relative to Cu-GGH and OV-3 alone. These data suggest that the Cu
      ATCUN derivatives inhibit bacteria by binding to the membrane, promoting
      oxidative damage of the lipids, which then disrupts the bilayer, resulting in
      cell death. This stands in contrast to the mode of action of OV-3 alone, which
      permeabilizes the membrane without lipid oxidation.

PMID- 29172481
TI  - Fucoxanthin and Its Metabolite Fucoxanthinol Do Not Induce Browning in Human
      Adipocytes.
AB  - Rodent studies suggest that the antiobesity effects of fucoxanthin relate to
      activation of brown fat and conversion of white adipocytes to the brown
      phenotype. To evaluate the browning effect in human adipocytes, we investigated
      the genes involved in browning and measured the oxygen consumption rate (OCR).
      Data were analyzed by one way ANOVA. Relative to control, fucoxanthinol (1 MUM,
      0.1 MUM, 0.01 MUM, 1 nM, 0.1 nM), the metabolite present in human plasma,
      stimulated lipolysis acutely (mean +/- SEM: 4.2 +/- 0.8, 3.1 +/- 0.6, 4.1 +/-
      0.9, 3.8 +/- 0.7, 3.8 +/- 0.7, respectively, p < 0.01). There was no effect on
      OCR or the mRNA expression of UCP1, CPT-1beta, and GLUT4, the genes associated
      with browning of adipose tissue, when human adipocytes were treated with
      fucoxanthin or fucoxanthinol. -mRNA expression of PGC-1alpha, PPARalpha,
      PPARgamma, PDK4, FAS, and the lipolytic enzymes was not significantly altered by
      fucoxanthinol treatment (p > 0.05). Thus, in human adipocytes, fucoxanthin and
      its metabolite do not stimulate conversion of white adipocytes to the brown
      phenotype.

PMID- 29172483
TI  - Gold(I) Alkynyls Supported by Mono- and Bidentate NHC Ligands: Luminescence and
      Isolation of Unprecedented Ionic Complexes.
AB  - Reactions of NHC.HX (NHC = 1-benzyl-3-methylbenzimidazol-2-ylidene, X = Br-, PF6
      ) and (AuC=CR)n (R = Ph, C3H6OH) in the presence of Cs2CO3 initially afford
      compounds of the general formula [(NHC)2Au]2[(RC2)2Au]X, which can be isolated by
      crystallization. With increased reaction time, only the expected mononuclear
      complexes of the type [NHCAuC=CR] are produced. The crystal structure of
      [(NHC)2Au]2[(PhC2)2Au]PF6 reveals an unprecedented triple-decker array upheld by
      a remarkably short (2.9375(7) A) unsupported Au...Au...Au contact. The
      mononuclear complex [NHCAuC=CPh] was found to crystallize as three distinct
      polymorphs and a pseudopolymorph, which depending on the intermolecular Au...Au
      distances emit blue, green, or yellow light. Two synthetic approaches were
      employed for the preparation of a series of dinuclear NHC-ligated Au(I) alkynyl
      complexes of the general formula [NHC-(CH2)n-NHC(AuC=CR)2], where NHC = N
      benzylbenzimidazol-2-ylidene, R = Ph, C3H6OH, C6H10OH, and n = 1-3. In solution,
      the complexes with aliphatic substituents on the alkynyl fragment are
      nonemissive, whereas their phenyl-bearing congeners demonstrate characteristic
      metal-perturbed 3[IL(C=CPh)] emission. In the solid state, a clear correlation
      between intermolecular aurophilic interactions and luminescence was established,
      including their role in the luminescent thermochromism of the phenylalkynyl
      complexes. The relationship between the Au...Au distance and emission energy was
      found to be inverse: i.e., the shorter the aurophilic contact, the higher the
      emission energy. We tentatively attribute this behavior to a smaller extent of
      excited-state distortion for a structure with a shorter Au...Au separation.

PMID- 29172484
TI  - Insulin-like Growth Factor 1 Analogs Clicked in the C Domain: Chemical Synthesis
      and Biological Activities.
AB  - Human insulin-like growth factor 1 (IGF-1) is a 70 amino acid protein hormone,
      with key impact on growth, development, and lifespan. The physiological and
      clinical importance of IGF-1 prompted challenging chemical and biological trials
      toward the development of its analogs as molecular tools for the IGF-1 receptor
      (IGF1-R) studies and as new therapeutics. Here, we report a new method for the
      total chemical synthesis of IGF-1 analogs, which entails the solid-phase
      synthesis of two IGF-1 precursor chains that is followed by the CuI-catalyzed
      azide-alkyne cycloaddition ligation and by biomimetic formation of a native
      pattern of disulfides. The connection of the two IGF-1 precursor chains by the
      triazole-containing moieties, and variation of its neighboring sequences (Arg36
      and Arg37), was tolerated in IGF-1R binding and its activation. These new
      synthetic IGF-1 analogs are unique examples of disulfide bonds' rich proteins
      with intra main-chain triazole links. The methodology reported here also presents
      a convenient synthetic platform for the design and production of new analogs of
      this important human hormone with non-standard protein modifications.

PMID- 29172485
TI  - Systematic Engineering of Single Substitution in Zirconium Metal-Organic
      Frameworks toward High-Performance Catalysis.
AB  - Zirconium-based metal-organic frameworks (Zr-MOFs) exhibit great structural
      tunability and outstanding chemical stability, rendering them promising
      candidates for a wide range of practical applications. In this work, we
      synthesized a series of isostructural PCN-224 analogues functionalized by ethyl,
      bromo, chloro, and fluoro groups on the porphyrin unit, which allowed us to
      explicitly study the effects of electron-donating and electron-withdrawing
      substituents on catalytic performance in MOFs. Owing to the different electronic
      properties of ethyl, bromo, chloro, and fluoro substitutes, the molecular-level
      control over the chemical environment surrounding a catalytic center could be
      readily achieved in our MOFs. To investigate the effects of these substitutes on
      catalytic activity and selectivity, the oxidation of 3-methylpentane to
      corresponding alcohols and ketones was utilized as a model reaction. Within these
      five analogues of PCN-224, an extremely high turnover number of 7680 and turnover
      frequency of 10 240 h-1 was achieved by simply altering the substitutes on
      porphyrin rings. Moreover, a remarkable 99% selectivity of the tertiary alcohol
      over the five other possible by-products are realized. We demonstrate that this
      strategy can be used to efficiently screen a suitable peripheral environment
      around catalytic cores in MOFs for catalysis.

PMID- 29172486
TI  - A Stable Isotope Dilution Nanoflow Liquid Chromatography Tandem Mass Spectrometry
      Assay for the Simultaneous Detection and Quantification of Glyoxal-Induced DNA
      Cross-Linked Adducts in Leukocytes from Diabetic Patients.
AB  - Glyoxal (gx) is a bifunctional electrophile capable of cross-linking DNA.
      Although it is present in foods and from the environment, endogenous formation of
      glyoxal occurs through metabolism of carbohydrates and oxidation of lipids and
      nucleic acids. Plasma concentrations of glyoxal are elevated in in diabetes
      mellitus patients compared to nondiabetics. The most abundant 2'
      deoxyribonucleoside adducts cross-linked by glyoxal are dG-gx-dC, dG-gx-dA, and
      dG-gx-dG. These DNA cross-links can be mutagenic by damaging the integrity of the
      DNA structure. Herein, we developed a highly sensitive and specific assay for the
      simultaneous detection and quantification of the dG-gx-dC and dG-gx-dA cross
      links based on stable isotope dilution (SID) nanoflow liquid chromatography
      nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) under the highly
      selected reaction monitoring mode and using a triple quadrupole mass
      spectrometer. The entire assay procedure involved addition of the stable isotope
      standards [15N5]dG-gx-dC and [15N5]dG-gx-dA as internal standards, enzyme
      hydrolysis to release the cross-links as nucleosides, enrichment by a reversed
      phase solid-phase extraction column, and nanoLC-NSI/MS/MS analysis. The detection
      limit is 0.19 amol for dG-gx-dC and 0.89 amol for dG-gx-dA, which is 400 and 80
      times more sensitive, respectively, than capillary LC-NSI/MS/MS assay of these
      adducts. The lower limit of quantification was 94 and 90 amol for dG-gx-dC and dG
      gx-dA, respectively, which is equivalent to 0.056 and 0.065 adducts in 108 normal
      nucleotides in 50 MUg of DNA. In type 2 diabetes mellitus (T2DM) patients (n =
      38), the levels of dG-gx-dC and dG-gx-dA in leukocyte DNA were 1.94 +/- 1.20 and
      2.10 +/- 1.77 in 108 normal nucleotides, respectively, which were significantly
      higher than those in nondiabetics (n = 39: 0.83 +/- 0.92 and 1.05 +/- 0.99 in 108
      normal nucleotides, respectively). Excluding the factor of smoking, an exogenous
      source of glyoxal, levels of these two cross-linked adducts were found to be
      significantly higher in nonsmoking T2DM patients than in nonsmoking control
      subjects. Furthermore, the levels of dG-gx-dC and dG-gx-dA correlated with HbA1c
      with statistical significance. To our best knowledge, this is the first report of
      the identification and quantification of glyoxal-derived cross-linked DNA adducts
      in human leukocyte DNA and their association with T2DM. This SID nanoLC-NSI/MS/MS
      assay is highly sensitive and specific and it requires only 50 MUg of leukocyte
      DNA isolated from 2-3 mL of blood to accurately quantify these two cross-linked
      adducts simultaneously. Our assay thus provides a useful biomarker for the
      evaluation of glyoxal-derived DNA damage.

PMID- 29172487
TI  - ZnO/gamma-Fe2O3 Charge Transfer Interface toward Highly Selective H2S Sensing at
      a Low Operating Temperature of 30  degrees C.
AB  - ZnO/gamma-Fe2O3 heterostructure has been deposited in the form of thin films
      using a single step facile electrochemical technique. Considering the unique
      properties of both ZnO and gamma-Fe2O3 toward the sensing of reducing gases, the
      concept of forming a heterostructure between them has been conceived. The
      structural characterization of the deposited material has been performed using X
      ray diffraction, field emission scanning electron microscopy, and transmission
      electron microscopy, which revealed a flowerlike morphology with the coexistence
      of both ZnO and gamma-Fe2O3 leading to the formation of a heterostructure. The
      material showed excellent sensing properties toward the selective detection of
      H2S at room temperature (30  degrees C) among the three test gases, namely, CH4,
      H2S, and CO. The effect of relative humidity was also studied to have an idea
      about the performance of the device under a real situation. The results are
      promising and better than those of many commercially available sensors. The room
      temperature selective detection will help in facile fabrication of portable
      gadgets.

PMID- 29172488
TI  - Identification of Allosteric Modulators of Metabotropic Glutamate 7 Receptor
      Using Proteochemometric Modeling.
AB  - Proteochemometric modeling (PCM) is a computational approach that can be
      considered an extension of quantitative structure-activity relationship (QSAR)
      modeling, where a single model incorporates information for a family of targets
      and all the associated ligands instead of modeling activity versus one target.
      This is especially useful for situations where bioactivity data exists for
      similar proteins but is scarce for the protein of interest. Here we demonstrate
      the application of PCM to identify allosteric modulators of metabotropic
      glutamate (mGlu) receptors. Given our long-running interest in modulating mGlu
      receptor function we compiled a matrix of compound-target bioactivity data. Some
      members of the mGlu family are well explored both internally and in the public
      domain, while there are much fewer examples of ligands for other targets such as
      the mGlu7 receptor. Using a PCM approach mGlu7 receptor hits were found. In
      comparison to conventional single target modeling the identified hits were more
      diverse, had a better confirmation rate, and provide starting points for further
      exploration. We conclude that the robust structure-activity relationship from
      well explored target family members translated to better quality hits for PCM
      compared to virtual screening (VS) based on a single target.

PMID- 29172489
TI  - Ligand-Directed Reactivity in Dioxygen and Water Binding to cis-[Pd(NHC)2(eta2
      O2)].
AB  - Reaction of [Pd(IPr)2] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)
      and O2 leads to the surprising discovery that at low temperature the initial
      reaction product is a highly labile peroxide complex cis-[Pd(IPr)2(eta2-O2)]. At
      temperatures ? -40  degrees C, cis-[Pd(IPr)2(eta2-O2)] adds a second O2 to form
      trans-[Pd(IPr)2(eta1-O2)2]. Squid magnetometry and EPR studies yield data that
      are consistent with a singlet diradical ground state with a thermally accessible
      triplet state for this unique bis-superoxide complex. In addition to reaction
      with O2, cis-[Pd(IPr)2(eta2-O2)] reacts at low temperature with H2O in
      methanol/ether solution to form trans-[Pd(IPr)2(OH)(OOH)]. The crystal structure
      of trans-[Pd(IPr)2(OOH)(OH)] is reported. Neither reaction with O2 nor reaction
      with H2O occurs under comparable conditions for cis-[Pd(IMes)2(eta2-O2)] (IMes =
      1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene). The increased reactivity of
      cis-[Pd(IPr)2(eta2-O2)] is attributed to the enthalpy of binding of O2 to
      [Pd(IPr)2] (-14.5 +/- 1.0 kcal/mol) that is approximately one-half that of
      [Pd(IMes)2] (-27.9 +/- 1.5 kcal/mol). Computational studies identify the cause as
      interligand repulsion forcing a wider C-Pd-C angle and tilting of the NHC plane
      in cis-[Pd(IPr)2(eta2-O2)]. Arene-arene interactions are more favorable and serve
      to further stabilize cis-[Pd(IMes)2(eta2-O2)]. Inclusion of dispersion effects in
      DFT calculations leads to improved agreement between experimental and
      computational enthalpies of O2 binding. A complete reaction diagram is
      constructed for formation of trans-[Pd(IPr)2(eta1-O2)2] and leads to the
      conclusion that kinetic factors inhibit formation of trans-[Pd(IMes)2(eta1-O2)2]
      at the low temperatures at which it is thermodynamically favored. Failure to
      detect the predicted T-shaped intermediate trans-[Pd(NHC)2(eta1-O2)] for either
      NHC = IMes or IPr is attributed to dynamic effects. A partial potential energy
      diagram for initial binding of O2 is constructed. A range of low-energy pathways
      at different angles of approach are present and blur the distinction between pure
      "side-on" or "end-on" trajectories for oxygen binding.

PMID- 29172490
TI  - Free Carrier Emergence and Onset of Electron-Phonon Coupling in Methylammonium
      Lead Halide Perovskite Films.
AB  - Sub-10 fs resolution pump-probe experiments on methylammonium lead halide
      perovskite films are described. Initial response to photoexcitation is assigned
      to localized hot excitons which dissociate to free carriers. This is attested to
      by band integrals of the pump-probe spectra where photoinduced bleaching rises
      abruptly 20 fs after photoexcitation. Later stages of spectral evolution are
      consistent with hot carrier cooling, during which state filling induced bleaching
      of interband and exciton transitions curiously more than doubles. Electron
      coupling to optical phonons is observed as periodic spectral modulations in the
      pump-probe data of both films. Fourier analysis identifies active phonons at ~100
      and 300 wavenumbers pertaining to the lead-halide framework and organic cation
      motions, respectively. Coupling strengths estimated from the depth of these
      modulations are in the weak coupling limit, in agreement with values extracted
      from temperature dependent emission line shape analysis. These findings support
      free carriers in these materials existing as large polarons. Accordingly, these
      modes are probably not dictating the moderate carrier mobility in this material.

PMID- 29172491
TI  - Nonchelated Phosphoniomethylidene Complexes of Scandium and Lutetium.
AB  - The first phosphoniomethylidene complexes of scandium and lutetium,
      [LLn(CHPPh3)X] (L = [MeC(NDIPP)CHC(NDIPP)Me]-; Ln = Sc, X = Me, I, TfO; Ln = Lu,
      X = CH2SiMe3), have been synthesized and fully characterized. DFT calculations
      clearly demonstrate the presence of an allylic Ln, C, P pi-type interaction in
      these complexes. X-ray diffraction indicates that the scandium iodide complex has
      the shortest Sc-C bond length to date (2.044(5) A). These phosphoniomethylidene
      complexes readily convert into the ylide complexes, and the reactivity is
      affected by both X- anion and Ln3+ ion. The reaction of lutetium complex with
      imine shows a rapid insertion of imine into the Lu-C(alkylidene) bond. DFT
      calculations indicate that, although the bonding situation seems similar to that
      of the scandium analog, the strong negative charge at the alkylidene carbon is
      not sufficiently screened by one hydrogen in the lutetium complex because of a
      more ionic bonding, and therefore, the reactivity of the lutetium complex is much
      higher.

PMID- 29172492
TI  - Preparation and Properties of a Novel Semi-IPN Slow-Release Fertilizer with the
      Function of Water Retention.
AB  - A new semi-interpenetrating polymer network (semi-IPN) slow-release fertilizer
      (SISRF) with water absorbency, based on the kaolin-g-poly(acrylic acid-co-acrylic
      amide) (kaolin-g-P(AA-co-AM)) network and linear urea-formaldehyde oligomers
      (UF), was prepared by solution polymerization. Nutrients phosphorus and potassium
      were supplied by adding dipotassium hydrogen phosphate during the preparation
      process. The structure and properties of SISRF were characterized by various
      characterization methods. SISRF showed excellent water absorbency of 68 g g-1 in
      tap water. The slow-release behavior of nutrients and water-retention capacity of
      SISRF were also measured. Meanwhile, the swelling kinetics was well described by
      a pseudo-second-order kinetics model. Results suggested the formation of SISRF
      with simultaneously good slow-release and water-retention capacity, which was
      expected to apply in modern agriculture and horticulture.

PMID- 29172493
TI  - Strategy for Hepatotoxicity Prediction Induced by Drug Reactive Metabolites Using
      Human Liver Microsome and Online 2D-Nano-LC-MS Analysis.
AB  - Hepatotoxicity is a leading cause of drug withdrawal from the market; thus, the
      assessment of potential drug induced liver injury (DILI) in preclinical trials is
      necessary. More and more research has shown that the covalent modification of
      drug reactive metabolites (RMs) for cellular proteins is a possible reason for
      DILI. Unfortunately, so far no appropriate method can be employed to evaluate
      this kind of DILI due to the low abundance of RM-protein adducts in complex
      biological samples. In this study, we proposed a mechanism-based strategy to
      solve this problem using human liver microsomes (HLMs) and online 2D nano-LC-MS
      analysis. First, RM modification patterns and potential modified AA residues are
      determined using HLM and model amino acids (AAs) by UHPLC-Q-TOF-MS. Then, a new
      online 2D-nano-LC-Q-TOF-MS method is established and applied to separate the
      digested modified microsomal peptides from high abundance peptides followed by
      identification of RM-modified proteins using Mascot, in which RM modification
      patterns on specific AA residues are added. Finally, the functions and
      relationship with hepatotoxicity of the RM-modified proteins are investigated
      using ingenuity pathway analysis (IPA) to predict the possible DILI. Using this
      strategy, 21 proteins were found to be modified by RMs of toosendanin, a
      hepatotoxic drug with complex structure, and some of them have been reported to
      be associated with hepatotoxicity. This strategy emphasizes the identification of
      drug RM-modified proteins in complex biological samples, and no pretreatment is
      required for the drugs. Consequently, it may serve as a valuable method to
      predict potential DILI, especially for complex compounds.

PMID- 29172494
TI  - Direct Synthesis of Secondary Benzylic Alcohols Enabled by Photoredox/Ni Dual
      Catalyzed Cross-Coupling.
AB  - An operationally simple, mild, redox-neutral method for the cross-coupling of
      alpha-hydroxyalkyltrifluoroborates is reported. Utilizing an Ir photocatalyst,
      alpha-hydroxyalkyl radicals are generated from the single-electron oxidation of
      the trifluoroborates, and these radicals are subsequently engaged in a nickel
      catalyzed C-C bond-forming reaction with aryl halides. The process is highly
      selective, functional group tolerant, and step economical, which allows the
      direct synthesis of secondary benzylic alcohol motifs.

PMID- 29172495
TI  - beta-Aminocarbonates in Regioselective and Ring Expansion Reactions.
AB  - The reactivity of beta-aminocarbonates as anisotropic electrophiles has been
      investigated with several phenols. Products distribution shows that the
      regioselectivity of the anchimerically driven alkylation reaction depends on the
      nucleophiles. The results suggest that in the presence of nucleophiles that are
      also good leaving groups, the reaction takes place under thermodynamic control
      favoring the attack on the most sterically hindered carbon of the cyclic
      aziridinium intermediate. Furthermore, when an enantiomerically pure pyrrolidine
      based carbonate was used, the reaction with phenols proceeds via a bicyclic
      aziridinium intermediate leading to the stereoselective synthesis of optically
      active 3-substituted piperidines via ring expansion reaction. These results were
      confirmed both by NMR spectroscopy and X-ray diffraction analysis.

PMID- 29172496
TI  - Antitubercular and Cytotoxic Chlorinated seco-Cyclohexenes from Uvaria alba.
AB  - Two new chlorine-containing polyoxygenated seco-cyclohexenes, albanols A (1) and
      B (2), along with the oxepinone metabolite grandiuvarone (3) were isolated from
      the endemic Philippine Annonaceae plant Uvaria alba. Both new compounds exhibited
      modest antitubercular activity. Compound 1 showed cytostatic activity (ranging
      from 1-50 MUM) against HeLa cells and weak antiproliferative activity against
      HUVEC and K-562 cells with GI50 values of 106 and 81 MUM, respectively.

PMID- 29172497
TI  - Diffusion Performance of Fertilizer Nutrient through Polymer Latex Film.
AB  - Matching the nutrient release rate of coated fertilizer with the nutrient uptake
      rate of the crop is the best way to increase the utilization efficiency of
      nutrients and reduce environmental pollution from the fertilizer. The diffusion
      property and mechanism of nutrients through the film are the theoretical basis
      for the product pattern design of coated fertilizers. For the coated fertilizer
      with a single-component nutrient, an extended solution-diffusion model was used
      to describe the difference of nutrient release rate, and the release rate is
      proportional to the permeation coefficient and the solubility of the nutrient.
      For the double- and triple-component fertilizer of N-K, N-P, and N-P-K, because
      of the interaction among nutrient molecules and ions, the release rates of
      different nutrients were significantly affected by the components in the
      composite fertilizer. Coating the single-component fertilizer (i.e., nitrogen
      fertilizer, phosphate fertilizer, and potash fertilizer) first and subsequently
      bulk blending is expected to be a promising way to adjust flexibly the nutrient
      release rate to meet the nutrient uptake rate of the crop.

PMID- 29172498
TI  - Reaction of H2 with O2 in Excited Electronic States: Reaction Pathways and Rate
      Constants.
AB  - Comprehensive quantum chemical analysis with the use of the multireference state
      averaged complete active space self-consistent field approach was carried out to
      study the reactions of H2 with O2 in a1Deltag, b1Sigmag+, c1Sigmau-, and
      A'3Deltau electronically excited states. The energetically favorable reaction
      pathways and possible intersystem crossings have been revealed. The energy
      barriers were refined employing the extended multiconfiguration quasi-degenerate
      second-order perturbation theory. It has been shown that the interaction of
      O2(a1Deltag) and O2(A'3Deltau) with H2 occurs through the H-abstraction process
      with relatively low activation barriers that resulted in the formation of the HO2
      molecule in A" and A' electronic states, respectively. Meanwhile, molecular
      oxygen in singlet sigma states (b1Sigmag+ and c1Sigmau-) was proved to be
      nonreactive with respect to the molecular hydrogen. Appropriate rate constants
      for revealed reaction and quenching channels have been estimated using
      variational transition-state theory including corrections for the tunneling
      effect, possible nonadiabatic transitions, and anharmonicity of vibrations for
      transition states and reactants. It was demonstrated that the calculated reaction
      rate constant for the H2 + O2(a1Deltag) process is in reasonable agreement with
      known experimental data. The Arrhenius approximations for these processes have
      been proposed for the temperature range T = 300-3000 K.

PMID- 29172500
TI  - Construction of Vibronic Diabatic Hamiltonian for Excited-State Electron and
      Energy Transfer Processes.
AB  - Photoinduced excited-state electron and energy transfer processes are crucial in
      biological photoharvesting systems and organic photovoltaic devices. We discuss
      the construction of a diabatic vibronic Hamiltonian for the proper treatment of
      these processes involving the projection approach acting on both electronic wave
      functions and vibrational modes. In the electronic part, the wave function
      projection approach is used to construct the diabatic Hamiltonian in which both
      local excited states and charge-transfer states are included on the same footing.
      For the vibrational degrees of freedom, the vibronic couplings in the diabatic
      Hamiltonian are obtained in the basis of the pseudonormal modes localized on each
      monomer site by applying delocalized-to-localized mode projection. This
      systematic approach allows us to construct the vibronic diabatic Hamiltonian in
      molecular aggregates.

PMID- 29172499
TI  - Release Properties and Cellular Uptake in Caco-2 Cells of Size-Controlled
      Chitosan Nanoparticles.
AB  - The influences of particle size on the physicochemical, release, and cellular
      uptake properties of chitosan nanoparticles (CSNPs) were investigated. Ionotropic
      CSNPs of different sizes (200-1000 nm) loaded with two model core materials
      (resveratrol or coumarin-6) were prepared using tripolyphosphate and carrageenan
      as cross-linkers. With an increase of particle size, zeta potential (34.6 +/- 0.5
      to 51.1 +/- 0.9) and entrapment efficiency (14.9 +/- 1.4 to 40.9 +/- 1.9) of the
      CSNPs were significantly (p < 0.05) increased and release rates were decreased.
      However, Caco-2 cellular uptake of CSNPs were significantly increased from 3.70
      +/- 0.03 to 5.24 +/- 0.20 with an increase of particle size from 200 to 600 nm,
      whereas those significantly decreased from 5.24 +/- 0.20 to 4.55 +/- 0.2 for
      particles larger than 600 nm in transwell assay. Moreover, much the same uptake
      patterns were also observed in confocal microscopy and flow cytometry.
      Investigation of cellular uptake of CSNPs revealed positive correlations between
      ZP and EE and indicated the effects of complex factors of nanoparticles other
      than size. These results provide a better understanding of CSNPs absorption and
      raises the possibility of controlling alternative nanoparticle properties to
      enhance bioavailability.

PMID- 29172501
TI  - Combined Phycocyanin and Hematoporphyrin Monomethyl Ether for Breast Cancer
      Treatment via Photosensitizers Modified Fe3O4 Nanoparticles Inhibiting the
      Proliferation and Migration of MCF-7 Cells.
AB  - Photodynamic therapy (PDT), combining the laser and photosensitizers to kill
      tumor cells, has the potential to address many current medical requirements. In
      this study, magnetic Fe3O4 nanoparticles were first employed as cores and
      modified with oleic acid (OA) and 3-triethoxysilyl-1-propanamine. Then, the
      photosensitizers phycocyanin (PC) and hematoporphyrin monomethyl ether (HMME),
      which might be able to stimulate the cell release of reactive oxygen species
      after the irradiation of a near-infrared (NIR) laser, were grafted on the surface
      of such nanoparticles. Our results revealed the high-efficiency inhibition of
      breast cancer MCF-7 cells growing upon near-infrared irradiation both in vitro
      and in vivo. Furthermore, it was the synergy between the natural photosensitizers
      PC and the synthetic photosensitizers HMME that deeply influenced such inhibition
      compared to the groups that used either of these medicines alone. To utilize the
      combination of different photosensitive agents, our study thus provides a new
      strategy for breast cancer treatment.

PMID- 29172502
TI  - Discovery and Optimization of Pyrrolopyrimidine Inhibitors of Interleukin-1
      Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88L265P
      Diffuse Large B-Cell Lymphoma.
AB  - Herein we report the optimization of a series of pyrrolopyrimidine inhibitors of
      interleukin-1 receptor associated kinase 4 (IRAK4) using X-ray crystal structures
      and structure based design to identify and optimize our scaffold. Compound 28
      demonstrated a favorable physicochemical and kinase selectivity profile and was
      identified as a promising in vivo tool with which to explore the role of IRAK4
      inhibition in the treatment of mutant MYD88L265P diffuse large B-cell lymphoma
      (DLBCL). Compound 28 was shown to be capable of demonstrating inhibition of NF
      kappaB activation and growth of the ABC subtype of DLBCL cell lines in vitro at
      high concentrations but showed greater effects in combination with a BTK
      inhibitor at lower concentrations. In vivo, the combination of compound 28 and
      ibrutinib led to tumor regression in an ABC-DLBCL mouse model.

PMID- 29172503
TI  - Optogenetic Control of Endoplasmic Reticulum-Mitochondria Tethering.
AB  - The organelle interface emerges as a dynamic platform for a variety of biological
      responses. However, their study has been limited by the lack of tools to
      manipulate their occurrence in live cells spatiotemporally. Here, we report the
      development of a genetically encoded light-inducible tethering (LIT) system
      allowing the induction of contacts between endoplasmic reticulum (ER) and
      mitochondria, taking advantage of a pair of light-dependent heterodimerization
      called an iLID system. We demonstrate that the iLID-based LIT approach enables
      control of ER-mitochondria tethering with high spatiotemporal precision in
      various cell types including primary neurons, which will facilitate the
      functional study of ER-mitochondrial contacts.

PMID- 29172504
TI  - Effect of Microbial Interaction on Urea Metabolism in Chinese Liquor
      Fermentation.
AB  - Urea is the primary precursor of the carcinogen ethyl carbamate in fermented
      foods. Understanding urea metabolism is important for controlling ethyl carbamate
      production. Using Chinese liquor as a model system, we used metatranscriptome
      analysis to investigate urea metabolism in spontaneous food fermentation
      processes. Saccharomyces cerevisiae was dominant in gene transcription for urea
      biosynthesis and degradation. Lysinibacillus sphaericus was dominant for urea
      degradation. S. cerevisiae degraded 18% and L. sphaericus degraded 13% of urea in
      their corresponding single cultures, whereas they degraded 56% of urea in
      coculture after 12 h. Compared to single cultures, transcription of CAR1, DAL2,
      and argA, which are related to urea biosynthesis, decreased by 51, 36, and 69% in
      coculture, respectively. Transcription of DUR1 and ureA, which are related to
      urea degradation, increased by 227 and 70%, respectively. Thus, coexistence of
      the two strains promoted degradation of urea via transcriptional regulation of
      genes related to urea metabolism.

PMID- 29172505
TI  - Synthesis of 3-Fluoropyridines via Photoredox-Mediated Coupling of alpha,alpha
      Difluoro-beta-iodoketones with Silyl Enol Ethers.
AB  - A method for the synthesis of diversely substituted 3-fluoropyridines from two
      ketone components is described. The reaction involves photoredox coupling of
      alpha,alpha-difluoro-beta-iodoketones with silyl enol ethers catalyzed by fac
      Ir(ppy)3 under blue LED irradiation with subsequent one-pot condensation with
      ammonium acetate. Based on cyclic voltammetry studies, it was determined that
      alpha,alpha-difluoro-beta-iodoketones are reduced notably easier compared to
      2,2,2-trifluoro-1-iodoethane, which may be ascribed to the influence of the
      carbonyl group.

PMID- 29172506
TI  - Potent Bis-Cyclometalated Iridium Photoreductants with beta-Diketiminate
      Ancillary Ligands.
AB  - In this work, we outline a strategy to prepare a class of improved visible-light
      photosensitizers. Bis-cyclometalated iridium complexes with electron-rich beta
      diketiminate (NacNac) ancillary ligands are demonstrated to be potent excited
      state electron donors. Evaluation of the photophysical and electrochemical
      properties establishes the excited-state redox potentials of the complexes, and
      Stern-Volmer quenching experiments inform on the kinetics of photoinduced
      electron transfer to the model substrates methyl viologen (MV2+) and benzophenone
      (BP). Compared to fac-Ir(ppy)3 (ppy = 2-phenylpyridine), widely regarded as a
      state-of-the-art photoreductant, the complexes we describe have excited-state
      redox potentials that are more potent by 300-400 mV and rates for photoinduced
      electron transfer that are accelerated by as much as a factor of 3. These
      complexes emerge as promising targets for application in photocatalytic reactions
      and other photochemical processes.

PMID- 29172507
TI  - A 36-Membered Ring Metal Chalcogenide with a Very Low Framework Density.
AB  - Reported here is a new open-framework metal chalcogenide containing extra-large
      36-ring channels. This compound has a 3-connected etc topology by regarding
      supertetrahedral T2 clusters as the structural nodes. It has a very low framework
      density (3.4 tetrahedra per 1000 A3) with each framework cation participating in
      three 3-rings. The organic cations within its intersecting channels can be
      partially exchanged out by Cs+ ions with the preservation of its framework
      structure.

PMID- 29172508
TI  - Low Cost, Fast Solution Synthesis of 3D Framework ZnO Nanosponges.
AB  - An efficient, template-free solution-chemical route to nanostructured ZnO sponges
      is presented: A mixture of Zn(NO3)2.6H2O, Zn(OAc)2.2H2O, and triethanolamine in
      methanol was evaporated to a highly viscous liquid and rapidly heated to >200 
      degrees C for 1-3 min to achieve highly porous, nanocrystalline sponges of ZnO.
      The viscous precursor concentrate obtained on evaporation in air was
      characterized by TG, DSC, and IR spectroscopy, and the product ZnO sponges by
      XRD, SEM, TEM, and IR spectroscopy. The fast reaction forming ZnO started at 140 
      degrees C and finished within a few seconds. Scherrer analysis of the XRD peak
      broadening showed average crystallite sizes of 8 to 11 nm for ZnO prepared by
      annealing at 200-450  degrees C (3 min), while grain growth to 134 nm was
      observed from 500 to 900  degrees C (3 min). The ZnO powders obtained at 200-900 
      degrees C had cell dimensions of a = 3.25 A and b = 5.21 A, matching the ZnO
      literature data well. SEM and TEM analyses showed highly porous, bread-like 3D
      nanostructures built by ca. 30-70 nm thick walls of ZnO crystallites of the
      approximate average sizes given by the XRD Scherrer analysis. It seems that the
      crystal growth above 450  degrees C takes place within the ZnO 3D structure
      obtained at lower temperatures without much sintering of the larger porous
      structure.

PMID- 29172509
TI  - Sequential Capture of O(3P) and HCN by Helium Nanodroplets: Infrared Spectroscopy
      and ab Initio Computations of the 3Sigma O-HCN Complex.
AB  - Catalytic thermal cracking of O2 is employed to dope helium droplets with O(3P)
      atoms. Mass spectrometry of the doped droplet beam reveals an O2 dissociation
      efficiency larger than 60%; approximately 26% of the droplet ensemble is doped
      with single oxygen atoms. Sequential capture of O(3P) and HCN leads to the
      production of a hydrogen-bound O-HCN complex in a 3Sigma electronic state, as
      determined via comparisons of experimental and theoretical rovibrational Stark
      spectroscopy. Ab initio computations of the three lowest lying intermolecular
      potential energy surfaces reveal two isomers, the hydrogen-bound (3Sigma) O-HCN
      complex and a nitrogen-bound (3Pi) HCN-O complex, lying 323 cm-1 higher in
      energy. The HCN-O to O-HCN interconversion barrier is predicted to be 42 cm-1.
      Consistent with this relatively small interconversion barrier, there is no
      experimental evidence for the production of the nitrogen-bound species upon
      sequential capture of O(3P) and HCN.

PMID- 29172510
TI  - Surrogate-Based Correlation Models in View of Real-Time Control of Ozonation of
      Secondary Treated Municipal Wastewater-Model Development and Dynamic Validation.
AB  - New robust correlation models for real-time monitoring and control of trace
      organic contaminant (TrOC) removal by ozonation are presented, based on UVA254
      and fluorescence surrogates, and developed considering kinetic information. The
      abatement patterns of TrOCs had inflected shapes, controlled by the reactivity of
      TrOCs toward ozone and HO* radicals. These novel and generic correlation models
      will be of importance for WRRF operators to reduce operational costs and minimize
      byproduct formation. Both UVA254 and fluorescence surrogates could be used to
      control DeltaTrOC, although fluorescence measurements indicated a slightly better
      reproducibility and an enlarged control range. The generic framework was
      validated for several WRRFs and correlations for any compound with known kinetic
      information could be developed solely using the second order reaction rate
      constant with ozone (kO3). Two distinct reaction phases were defined for which
      separate linear correlations were obtained. The first was mainly ozone
      controlled, while the second phase was more related to HO* reactions.
      Furthermore, parallel factor analysis of the fluorescence spectra enabled
      monitoring of multiple types of organic matter with different O3 and HO*
      reactivity. This knowledge is of value for kinetic modeling frameworks and for
      achieving a better understanding of the occurring changes of organic matter
      during ozonation.

PMID- 29172511
TI  - Further Investigation of the Intermolecular Diels-Alder Cycloaddition for the
      Synthesis of Bicyclo[2.2.2]diazaoctane Alkaloids.
AB  - The convergent synthesis of bicyclo[2.2.2]diazaoctane structures using an
      intermolecular Diels-Alder cycloaddition between a pyrazinone and commercially
      available fumarate or maleate precursors is reported. High reactivity and
      stereoselection is observed with both dienophile substrates. Structure validation
      was achieved by conversion of cycloadducts into known [2.2.2]diazabicyclic
      compounds or into crystalline derivatives suitable for X-ray analysis. The
      cycloadduct derived from reaction of pyrazinone and maleic anhydride underwent
      selective anhydride ring opening and intersected an established precursor in the
      synthesis of brevianamide B.

PMID- 29172512
TI  - Structural and Dynamical Impact of a Universal Fluorescent Nucleoside Analogue
      Inserted Into a DNA Duplex.
AB  - Recently, a 3-hydroxychromone based nucleoside 3HCnt has been developed as a
      highly environment-sensitive nucleoside surrogate to investigate protein-DNA
      interactions. When it is incorporated in DNA, the probe is up to 50-fold brighter
      than 2-aminopurine, the reference fluorescent nucleoside. Although the insertion
      of 3HCnt in DNA was previously shown to not alter the overall DNA structure, the
      possibility of the probe inducing local effects cannot be ruled out. Hence, a
      systematic structural and dynamic study is required to unveil the 3HCnt's
      limitations and to properly interpret the data obtained with this universal
      probe. Here, we investigated by NMR a 12-mer duplex, in which a central adenine
      was replaced by 3HCnt. The chemical shifts variations and nOe contacts revealed
      that the 3HCnt is well inserted in the DNA double helix with extensive stacking
      interactions with the neighbor base pairs. These observations are in excellent
      agreement with the steady-state and time-resolved fluorescence properties
      indicating that the 3HCnt fluorophore is protected from the solvent and does not
      exhibit rotational motion. The 3HCnt insertion in DNA is accompanied by the
      extrusion of the opposite nucleobase from the double helix. Molecular dynamics
      simulations using NMR-restraints demonstrated that 3HCnt fluorophore exhibits
      only translational dynamics. Taken together, our data showed an excellent
      intercalation of 3HCnt in the DNA double helix, which is accompanied by localized
      perturbations. This confirms 3HCnt as a highly promising tool for nucleic acid
      labeling and sensing.

PMID- 29172513
TI  - Regioselective C-H Bond Alkynylation of Carbonyl Compounds through Ir(III)
      Catalysis.
AB  - Selective C-H bond alkynylation toward modular access to material and
      pharmaceutical molecules is of great desire in modern organic synthesis. Reported
      herein is Ir(III)-catalyzed regioselective C-H alkynylation of ketones and
      esters, which is generally applicable for the rapid construction of molecular
      complexity. This protocol provides a complementary process for conventional
      alkyne synthesis. Further functionalization of carbonyl-derived material
      molecules and pharmaceuticals demonstrates the potential synthetic utility of
      this methodology.

PMID- 29172514
TI  - Thiol Reactivity toward Atomic Oxygen Generated during the Photodeoxygenation of
      Dibenzothiophene S-Oxide.
AB  - Aromatic heterocyclic oxides, such as dibenzothiophene S-oxide (DBTO), have been
      suggested to release ground state atomic oxygen [O(3P)] upon irradiation, and as
      such, they have been used to create a condensed phase reactivity profile for
      O(3P). However, thiols, which are highly reactive with O(3P) in the gas phase,
      were not previously investigated. An earlier study of O(3P) with proteins in
      solution indicated a preference for thiols. A further investigation of the
      apparent thiophilicity provided the subject for this study. DBTO was employed as
      a putative O(3P)-precursor. However, the effective rate of O(3P) formation was
      found to be dependent on reactant concentrations in certain cases. All reactants
      were found to increase the rate of deoxygenation to some extent, but in the
      presence of reactants containing an alcohol linked to a reactive functional
      group, deoxygenation occurred substantially more rapidly. The rate enhancement
      was quantified and attributed to the reaction of activated O atom within the
      solvent cage prior to escape into the bulk solution. Through competition
      experiments, the relative rate constants of O(3P) with thiols and other
      functional groups were found. A small preference for primary thiols was observed
      over other thiols, sulfides, and alkenes. A much larger preference was observed
      for thiols, sulfides, and alkenes over aromatic groups. In summary, DBTO was
      successfully used as an O(3P)-precursor, and the thiophilicity of O(3P) was
      confirmed and quantified.

PMID- 29172515
TI  - Understanding the Inhibiting Effect of Small-Molecule Hydrogen Bond Donors on the
      Solubility of Cellulose in Tetrabutylammonium Acetate/DMSO.
AB  - Certain ionic liquids are powerful cellulose solvents, but tend to be less
      effective when small-molecule hydrogen bond donors are present. This is generally
      attributed to competition with cellulose for hydrogen bonding opportunities to
      the anion of the ionic liquid. We show that the solubility of cellulose in
      dimethyl sulfoxide solutions of tetrabutylammonium acetate is less strongly
      affected by water than by ethanol on a molar basis, contrary to what can be
      expected based on hydrogen bond stoichiometry. Molecular dynamics simulations
      indicate that the higher tolerance to water is due to water-cellulose
      interactions that improves solvation of cellulose and, thereby, marginally favors
      dissolution. Through Kirkwood-Buff theory we show that water, but not ethanol,
      improves the solvent quality of DMSO and partly compensates for the loss of
      acetate-cellulose hydrogen bonds.

PMID- 29172516
TI  - Improvement of Human-Oral-Epithelial-Barrier Function and of Tight Junctions by
      Micronutrients.
AB  - The oral epithelium represents a major interface between an organism and its
      external environment. Improving this barrier at the molecular level can provide
      an organism added protection from microbial-based diseases. Barrier function of
      the Gie-3B11-human-gingival-epithelial-cell-culture model is enhanced by the
      micronutrients zinc, quercetin, retinoic acid, and acetyl-11-keto-beta-boswellic
      acid, as observed by a concentration-dependent increase in transepithelial
      electrical resistance and a decrease in transepithelial 14C-d-mannitol
      permeability. With this improvement of tight-junction (TJ)-barrier function
      (reduced leak) comes a pattern of micronutrient-induced changes in TJ claudin
      abundance that is specific to each individual micronutrient, along with changes
      in claudin subcellular localization. These micronutrients were effective not only
      when administered to both cell surfaces simultaneously but also when administered
      to the apical surface alone, the surface to which the micronutrients would be
      presented in routine clinical use. The biomedical implications of micronutrient
      enhancement of the oral-epithelial barrier are discussed.

PMID- 29172517
TI  - Influence of Multiple Environmental Factors on Organic Matter Chlorination in
      Podsol Soil.
AB  - Natural chlorination of organic matter is common in soils. The abundance of
      chlorinated organic compounds frequently exceeds chloride in surface soils, and
      the ability to chlorinate soil organic matter (SOM) appears widespread among
      microorganisms. Yet, the environmental control of chlorination is unclear.
      Laboratory incubations with 36Cl as a Cl tracer were performed to test how
      combinations of environmental factors, including levels of soil moisture,
      nitrate, chloride, and labile organic carbon, influenced chlorination of SOM from
      a boreal forest. Total chlorination was hampered by addition of nitrate or by
      nitrate in combination with water but enhanced by addition of chloride or most
      additions including labile organic matter (glucose and maltose). The greatest
      chlorination was observed after 15 days when nitrate and water were added
      together with labile organic matter. The effect that labile organic matter
      strongly stimulated the chlorination rates was confirmed by a second independent
      experiment showing higher stimulation at increased availability of labile organic
      matter. Our results highlight cause-effect links between chlorination and the
      studied environmental variables in podsol soil-with consistent stimulation by
      labile organic matter that did overrule the negative effects of nitrate.

PMID- 29172519
TI  - xMaP-An Interpretable Alignment-Free Four-Dimensional Quantitative Structure
      Activity Relationship Technique Based on Molecular Surface Properties and
      Conformer Ensembles.
AB  - A novel alignment-free molecular descriptor called xMaP (flexible MaP descriptor)
      is introduced. The descriptor is the advancement of the previously published
      translationally and rotationally invariant three-dimensional (3D) descriptor MaP
      (mapping property distributions onto the molecular surface) to the fourth
      dimension (4D). In addition to MaP, xMaP is independent of the chosen starting
      conformation of the encoded molecules and is therefore entirely alignment-free.
      This is achieved by using ensembles of conformers, which are generated by
      conformational searches. This step of the procedure is similar to Hopfinger's 4D
      quantitative structure-activity relationship (QSAR). A five-step procedure is
      used to compute the xMaP descriptor. First, a conformational search for each
      molecule is carried out. Next, for each of the conformers an approximation to the
      molecular surface with equally distributed surface points is computed. Third,
      molecular properties are projected onto this surface. Fourth, areas of identical
      properties are clustered to so-called patches. Fifth, the spatial distribution of
      the patches is converted into an alignment-free descriptor that is based on the
      entire conformer ensemble. The resulting descriptor can be interpreted by
      superimposing the most important descriptor variables and the molecules of the
      data set. The most important descriptor variables are identified with chemometric
      regression tools. The novel descriptor was applied to several benchmark data sets
      and was compared to other descriptors and QSAR techniques comprising a binary
      fingerprint, a topological pharmacophore descriptor (Cats2D), and the field-based
      3D-QSAR technique GRID/PLS which is alignment-dependent. The use of conformer
      ensembles renders xMaP very robust. It turns out that xMaP performs very well on
      (almost) all data sets and that the statistical results are comparable to
      GRID/PLS. In addition to that, xMaP can also be used to efficiently visualize the
      derived quantitative structure-activity relationships.

PMID- 29172518
TI  - Ergot Alkaloid Biosynthesis in the Maize (Zea mays) Ergot Fungus Claviceps
      gigantea.
AB  - Biosynthesis of the dihydrogenated forms of ergot alkaloids is of interest
      because many of the ergot alkaloids used as pharmaceuticals may be derived from
      dihydrolysergic acid (DHLA) or its precursor dihydrolysergol. The maize (Zea
      mays) ergot pathogen Claviceps gigantea has been reported to produce
      dihydrolysergol, a hydroxylated derivative of the common ergot alkaloid
      festuclavine. We hypothesized expression of C. gigantea cloA in a festuclavine
      accumulating mutant of the fungus Neosartorya fumigata would yield
      dihydrolysergol because the P450 monooxygenase CloA from other fungi performs
      similar oxidation reactions. We engineered such a strain, and high performance
      liquid chromatography and liquid chromatography-mass spectrometry analyses
      demonstrated the modified strain produced DHLA, the fully oxidized product of
      dihydrolysergol. Accumulation of high concentrations of DHLA in field-collected
      C. gigantea sclerotia and discovery of a mutation in the gene lpsA, downstream
      from DHLA formation, supported our finding that DHLA rather than dihydrolysergol
      is the end product of the C. gigantea pathway.

PMID- 29172520
TI  - Copper(I) Chelators for Alzheimer's Disease.
AB  - A component of the neurotoxicity of the beta amyloid peptide (Abeta) of
      Alzheimer's disease is its ability to generate superoxide, hydrogen peroxide, and
      hydroxyl radicals by reaction of its reduced copper complex Abeta/Cu+ with
      molecular oxygen. The objective of the present work was to devise compounds, L,
      that could remove Cu+ from Abeta/Cu+, with the property that L/Cu+ itself would
      not be capable of reducing O2 or hydrogen peroxide. We show by density functional
      calculations that several pincer-type compounds with two imidazole rings and a
      sulfur or nitrogen have the desired combination of Cu+ binding affinity and Cu2+
      reduction potential.

PMID- 29172521
TI  - Small Peptides Isolated from Enzymatic Hydrolyzate of Fermented Soybean Meal
      Promote Endothelium-Independent Vasorelaxation and ACE Inhibition.
AB  - Fermentation of soybean is a process in which soy proteins are broken down into
      small peptides to exert various physiological functions beyond their nutritional
      value and to improve food source bioactive components responsible for health
      benefits. Enzymatic hydrolysis could speed up the degradation of proteins during
      fermentation of soybean, thus resulting in higher peptide production. In the
      present study, fermented soy meal (fermented with Bacillus subtilis from Douchi)
      was hydrolyzed by thermolysin, and the water extraction was then separated into
      four fractions using ultrafiltration membranes. Their vasorelaxation activities
      were screened, and the most potent fraction was further isolated and purified to
      obtain four peptides. Briefly, three peptides exerted a dose-dependent
      vasorelaxation (0.01-4.10 MUM) in the phenylephrine preconstricted thoracic aorta
      ring of Sprague-Dawley rat (relaxation actions were all endothelium-independent),
      while one peptide induced vasoconstriction. Furthermore, an independent causal
      relationship between vasorelaxation and angiotensin converting enzyme (ACE)
      inhibition activities was found.

PMID- 29172522
TI  - Small-Angle X-ray Crystallography on Single-Crystal Regions of Inverse
      Bicontinuous Cubic Phases: Lipid Bilayer Structures and Gaussian Curvature
      Dependent Fluctuations.
AB  - I report for the first time an X-ray crystallographic study on single-crystal
      regions of cubic phases of a lyotropic liquid crystal. The single-crystal regions
      of three inverse bicontinuous cubic phases of a lipid, monoolein, diffracted X
      ray only in small-angle regions, but amplitudes of structure factors were
      determined from the small-angle X-ray diffraction data with high accuracy.
      Structure factors from lipid bilayer models with constant thickness were
      optimized to amplitudes obtained from the X-ray data. By using amplitudes of the
      structure factors from X-ray data and phases from the models, electron density
      maps of three cubic phases were reconstructed. Lipid bilayer membranes,
      consisting of high density head regions and low density tail regions, were
      clearly distinguished in the electron density maps. Water regions had slightly
      lower density than that of the lipid head regions and were clearly visible for
      two of the cubic phases. Centers of bilayer membranes were located on the
      corresponding triply periodic minimal surfaces in the maps. Electron density data
      indicated Gaussian curvature-dependent fluctuations of bilayer membranes: the
      smaller the Gaussian curvature is, the larger the fluctuation becomes. The
      technique described in this report is expected to bring new knowledge in the
      structural research of lyotropic liquid crystals.

PMID- 29172523
TI  - Direct Microscopic Analysis of Individual C60 Dimerization Events: Kinetics and
      Mechanisms.
AB  - Modern transition state theory states that the statistical behavior of a chemical
      reaction is the sum of individual chemical events that occur randomly.
      Statistical analysis of each event for individual molecules in a three
      dimensional space however is practically impossible. We report here that kinetics
      and mechanisms of chemical reactions can be investigated by using a one
      dimensional system where reaction events can be observed in situ and counted one
      by one using variable-temperature (VT) atomic-resolution transmission electron
      microscopy (TEM). We thereby provide direct proof that the ensemble behavior of
      random events conforms to the Rice-Ramsperger-Kassel-Marcus theory, as
      illustrated for [2 + 2] cycloaddition of C60 molecules in carbon nanotubes
      (CNTs). This method gives kinetic and structural information for different types
      of reactions occurring simultaneously in the microscopic view field, suggesting
      that the VT-TEM opens a new dimension of chemical kinetics research on molecules
      and their assemblies in their excited and ionized states. The study carried out
      at 393-493 K showed that pristine CNT primarily acts as a singlet sensitizer of
      the cycloaddition reaction that takes place with an activation energy of 33.5 +/-
      6.8 kJ/mol. On the other hand, CNT suffers electron damage of the conjugated
      system at 103-203 K and promotes a reactive radical cation path that takes place
      with an activation energy of only 1.9 +/- 0.7 kJ/mol. The pre-exponential factor
      of the Arrhenius plot gave us further mechanistic insights.

PMID- 29172524
TI  - Optimization of a Protease Activated Probe for Optical Surgical Navigation.
AB  - Molecularly targeted optical contrast agents have the potential to enable
      surgeons to visualize specific molecular markers that can help improve surgical
      precision and thus outcomes. Fluorescently quenched substrates can be used to
      highlight tumor lesions by targeting proteases that are highly abundant in the
      tumor microenvironment. However, the majority of these and other molecularly
      targeted optical contrast agents are labeled with reporter dyes that are not
      ideally matched to the properties of clinical camera systems, which are typically
      optimized for detection of indocyanine-green (ICG). While a wide range of near
      infrared (NIR) dyes are suitable for use with highly sensitive and highly tunable
      research-focused small animal imaging systems, most have not been evaluated for
      use with commonly used clinical imaging systems. Here we report the optimization
      of a small molecule fluorescently quenched protease substrate probe 6QC-ICG,
      which uses the indocyanine green (ICG) dye as its optical reporter. We evaluated
      dosing and kinetic parameters of this molecule in tumor-bearing mice and observed
      optimal tumor over background signals in as little as 90 min with a dose of 2.3
      mg/kg. Importantly, the fluorescence intensity of the probe signal in tumors did
      not linearly scale with dose, suggesting the importance of detailed dosing
      studies. Furthermore, when imaged using the FDA approved da Vinci Si surgical
      system with Firefly detection, signals were significantly higher for the ICG
      probe compared to a corresponding probe containing a dye with similar quantum
      yield but with a slightly shifted excitation and emission profile. The increased
      signal intensity generated by the optimal dye and dose of the ICG labeled probe
      enabled detection of small, flat lesions that were less than 5 mm in diameter.
      Therefore, 6QC-ICG is a highly sensitive probe that performs optimally with
      clinical imaging systems and has great potential for applications in optical
      surgical navigation.

PMID- 29172525
TI  - Role of Bath Fluctuations in the Double-Excitation Manifold in Shaping the 2DES
      of Bacterial Reaction Centers at Low Temperature.
AB  - Spectroscopically relevant properties in photosynthetic reaction centers change
      during charge separation. In this paper, we focus on incorporation of the
      complete set of environmental fluctuations in the modeling of the nonlinear
      spectra of molecular aggregates. The model is applied in simulations of two
      dimensional electronic spectra of a photosynthetic reaction center at low
      temperature (5 K), where spectral lines are narrow, such that more features can
      be resolved. We show that vertical cross sections of the simulated two
      dimensional spectra (with all populations in the lowest excited state) reveal
      transient hole-burned spectra excited resonantly within the B band in agreement
      with experiment, thus providing new insight into environmental fluctuation
      parameters of Rhodobacter sphaeroides at low temperatures. Correlated
      fluctuations of molecular parameters are found to be necessary to describe charge
      separated configurations of molecular excited states.

PMID- 29172526
TI  - Stronger Intermolecular Forces or Closer Molecular Spacing? Key Impact Factor
      Research of Gelator Self-Assembly Mechanism.
AB  - The benzene ring of low-molecular-weight gelators provides strong intermolecular
      forces but increases molecular spacing during self-assembly. To explore both of
      the above influences on the gel properties, we synthesize two gelators (Glu-CBZ
      and Glu-DPA) consisting of the same terminal long side chain but different
      aliphatic functional groups. The aliphatic functional groups are carbobenzoxy
      group and diphenyl phosphate group. The self-assembly driving forces, self
      organization patterns, network morphologies, rheological properties, and the
      influences of solvents are researched through 1H NMR spectra, Fourier transform
      infrared spectra, field-emission scanning electron microscopy images, rheological
      characterizations curves, tube-inversion experiment, and calculation of van't
      Hoff plots. The results show that the carbobenzoxy group of Glu-CBZ makes
      molecules pack more tightly such that it improves the gel properties during
      static equilibrium. Whereas the diphenyl phosphate group of Glu-DPA provides
      stronger intermolecular forces, performing outstandingly during dynamic
      equilibrium. It is advantageous to further investigate the competitive
      relationship in gel system between the increased number of functional groups and
      the consequent steric effect.

PMID- 29172527
TI  - Isotopically-Labeled Iodoacetamide-Alkyne Probes for Quantitative Cysteine
      Reactivity Profiling.
AB  - Cysteine residues on proteins serve a variety of catalytic and regulatory
      functions due to the high nucleophilicity and redox activity of the thiol group.
      Quantitative proteomic platforms for profiling cysteine reactivity can provide
      valuable information related to the post-translational modification state and
      inhibitor occupancy of functional cysteine residues within a complex proteome.
      Cysteine-reactivity profiling typically monitors changes in the extent of
      cysteine labeling by cysteine-reactive chemical probes, such as iodoacetamide
      (IA)-alkyne. To enable accurate measurements of cysteine reactivity changes,
      isotopic labels are introduced into the two proteomes of interest using either
      isotopically tagged proteomes (SILAC) or cleavable linkers (isoTOP-ABPP) that are
      installed using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Here we
      provide an alternative strategy for isotopic tagging of two proteomes for
      cysteine-reactivity profiling by developing IA-light and IA-heavy, a pair of
      isotopically labeled iodoacetamide-alkyne probes. These probes can be utilized
      for proteome samples that are not amenable to SILAC labeling and are facile to
      synthesize, especially when compared to the isotopically tagged cleavable
      linkers. We confirm the quantitative accuracy of IA-light and IA-heavy by
      assessing cysteine reactivity in a purified thioredoxin protein, as well as
      globally within a complex proteome where IA-light treatment generates mass
      spectrometry identification of 992 cysteine residues. Importantly, these
      isotopically tagged probes can also be utilized for quantifying the percentage of
      cysteine modification within a single sample. Preliminary data supports the use
      of these tags to quantify the stoichiometry of TCEP-susceptible cysteine
      oxidation events in cell lysates.

PMID- 29172528
TI  - Novel Sigma Receptor Ligand-Nitric Oxide Photodonors: Molecular Hybrids for
      Double-Targeted Antiproliferative Effect.
AB  - This contribution reports the synthesis and evaluation of novel hybrid compounds
      that conjugate a sigma (sigma) receptor pharmacophore and a nitric oxide (NO)
      photodonor. All compounds preserve their capability to generate NO under visible
      light and possess overall sigma receptor nanomolar affinity, with one of them
      (8b) exhibiting remarkable sigma2 receptor selectivity. Compounds 8b, 11a, and
      11b were tested on tumorigenic MCF-7 and A2058 cells expressing high levels of
      sigma2 and sigma1 receptor, respectively. Considerable loss of cell viability was
      detected under light excitation, while negligible effects in the dark were
      detected. Moreover, they did not show any significant cytotoxicity in the dark or
      under irradiation on nontumorigenic NCTC-2544 keratinocytes. NO-induced reduction
      of cellular viability was demonstrated by in-cell NO detection and total nitrite
      estimation. For the first time, a combination of sigma receptor moieties and a NO
      photodonor is reported, providing distinctive ligands potentially useful for
      cancer management.

PMID- 29172529
TI  - Facile and Rapid Growth of Nanostructured Ln-BTC Metal-Organic Framework Films by
      Electrophoretic Deposition for Explosives sensing in Gas and Cr 3+ Detection in
      Solution.
AB  - Until now, it has been a challenge to prepare lanthanide metal-organic framework
      films on traditional substrates, like zinc plate, indium oxide (ITO), and
      fluorine-doped tin oxide (FTO) glasses in a rapid and facile method. In this
      paper, continuous and dense Ln-BTC MOFs films on unmodified low-cost substrates
      have been rapidly and easily fabricated though the newly developed
      electrophoretic deposition (EPD) method in 5 min. Moreover, the as-prepared
      luminescent films were successfully used for the detection of nitrobenzene (NB),
      trinitrotoluene (TNT) in gas phases, as well as NB, Cr3+ ions for detection in
      solution.

PMID- 29172530
TI  - Effect of Ethanethiolate Spacer on Morphology and Optical Responses of Ag
      Nanoparticle Array-Single Layer Graphene Hybrid Systems.
AB  - Single layer graphene (SLG) and two-dimensional (2-D) plasmonic Ag nanoparticle
      arrays assembled by chemisorption of ethanethiol (ET) molecules (AgNPs-ET) were
      employed as components of two types of hybrid systems designed for surface
      enhanced Raman scattering (SERS) spectral probing of SLG localized in the
      vicinity of plasmonic NPs. Both hybrids were characterized by optical microscopy,
      transmission electron microscopy (TEM), surface plasmon extinction (SPE), and
      SERS microRaman spectral measurements at four excitation wavelengths spanning the
      445-780 nm range. SERS spectral probing of the glass/SLG/AgNPs-ET hybrid prepared
      by overdeposition of SLG on glass by the array of ET-modified Ag NPs has shown
      that the chemisorbed ET acts as an efficient molecular spacer between SLG and Ag
      NPs surface which, in turn, enabled to obtain SERS spectra of SLG unperturbed by
      doping or strain. TEM imaging and SERS spectral probing of the second hybrid
      prepared by overdeposition of AgNPs-ET array on glass by SLG revealed removal of
      the adsorbed ET molecules and annealing of Ag NPs during the SLG deposition. The
      characteristics of the resulting glass/AgNPs/SLG hybrid system, namely (i) broad
      distribution of the annealed Ag NPs sizes and shapes, (ii) SPE curve covering the
      overall visible spectral region, (iii) absence of the ET spectral bands in SERS
      spectra, and (iv) fairly uniform SERS enhancement of the G and 2D mode of SLG in
      the 532-780 nm range in the straight sample geometry indicate that this hybrid
      can provide a suitable platform for investigation of the excitation wavelength
      dependence of combined SERS/GERS (graphene-enhanced Raman scattering) enhancement
      experienced by various molecular species brought into contact with SLG in this
      hybrid. Finally, weak optical effects attributed to increased reflectivity of SLG
      in the near field of Ag NPs arrays have been observed in the excitation
      wavelength dependence of the SERS spectra of both types of hybrid systems.

PMID- 29172531
TI  - Visible Light Organic Photoredox-Catalyzed C-H Alkoxylation of Imidazopyridine
      with Alcohol.
AB  - The visible light-mediated C-3 alkoxylation of imidazopyridines with alcohols has
      been achieved using rose bengal as an organic photoredox catalyst at room
      temperature. Widely abundant air acts as the terminal oxidant that avoids the use
      of a stoichiometric amount of peroxo compounds. A wide range of functional groups
      could be tolerated under the reaction conditions to produce C(sp2)-H alkoxylated
      products in high yields.

PMID- 29172532
TI  - Enhancing Mucosal Immune Response of Newcastle Disease Virus DNA Vaccine Using N
      2-Hydroxypropyl Trimethylammonium Chloride Chitosan and N,O-Carboxymethyl
      Chitosan Nanoparticles as Delivery Carrier.
AB  - Because mucosal sites are the entry ports of pathogens, immunization via mucosal
      routes can extremely enhance the immunity. To elevate the potential of N-2
      hydroxypropyl trimethylammonium chloride chitosan (N-2-HACC) and N,O
      carboxymethyl chitosan (CMC) nanoparticles as a mucosal immune delivery carrier
      for DNA vaccines, we prepared the NDV F gene plasmid DNA with C3d6 molecular
      adjuvant (pVAX I-F(o)-C3d6) encapsulated in the N-2-HACC-CMC nanoparticles (N-2
      HACC-CMC/pFDNA-C3d6 NPs). The N-2-HACC-CMC/pFDNA-C3d6 NPs had regular spherical
      morphology and low toxicity with a mean diameter of 309.7 +/- 6.52 nm, zeta
      potential of 49.9 +/- 4.93 mV, encapsulation efficiency of 92.27 +/- 1.48%, and
      loading capacity of 50.75 +/- 1.35%. The N-2-HACC-CMC had high stability and
      safety. The pVAX I-F(o)-C3d6 could be sustainably released from the N-2-HACC
      CMC/pFDNA-C3d6 NPs after an initial burst release. Immunization intranasally of
      chickens with N-2-HACC-CMC/pFDNA-C3d6 NPs not only produced higher anti-NDV IgG
      and sIgA antibody than chickens in other groups did, but also significantly
      stimulated lymphocyte proliferation and triggered higher the IL-2, IL-4, and IFN
      gamma levels. These findings indicated that the N-2-HACC-CMC could be used as an
      efficient delivery carrier for the mucosal immunity of Newcastle disease virus
      DNA vaccine. The work laid a basis for the quaternized chitosan nanoparticles as
      efficient mucosal immunity delivery carrier for DNA vaccines and had immense
      application promise and potential for vaccines and drugs.

PMID- 29172533
TI  - Experimental Study of Diesel-Fuel Droplet Impact on a Similarly Sized Polished
      Spherical Heated Solid Particle.
AB  - The head-to-head impact of diesel-fuel droplets on a polished spherical brass
      target has been investigated experimentally. High-speed imaging was employed to
      visualize the impact process for wall surface temperatures and Weber and Reynolds
      numbers in the ranges of 140-340  degrees C, 30-850, and 210-1135, respectively.
      The thermohydrodynamic outcome regimes occurring for the aforementioned ranges of
      parameters were mapped on a We-T diagram. Seven clearly distinguishable
      postimpact outcome regimes were identified, which are conventionally called the
      coating, splash, rebound, breakup-rebound, splash-breakup-coating, breakup
      coating, and splash-breakup-rebound regimes. In addition, the effects of the
      Weber number and surface temperature on the wettability dynamics were examined;
      the temporal variations of the dynamic contact angle, dimensionless spreading
      diameter, and liquid film thickness forming on the solid particle were measured
      and are reported.

PMID- 29172534
TI  - Early Dynamics and Stabilization Mechanisms of Oil-in-Water Emulsions Containing
      Colloidal Particles Modified with Short Amphiphiles: A Numerical Study.
AB  - Emulsions stabilized by mixtures of particles and amphiphilic molecules are
      relevant for a wide range of applications, but their dynamics and stabilization
      mechanisms on the colloidal level are poorly understood. Given the challenges to
      experimentally probe the early dynamics and mechanisms of droplet stabilization,
      Brownian dynamics simulations are developed here to study the behavior of oil-in
      water emulsions stabilized by colloidal particles modified with short
      amphiphiles. Simulation parameters are based on an experimental system that
      consists of emulsions obtained with octane as the oil phase and a suspension of
      alumina colloidal particles modified with short carboxylic acids as the
      continuous aqueous medium. The numerical results show that attractive forces
      between the colloidal particles favor the formation of closely packed clusters on
      the droplet surface or of a percolating network of particles throughout the
      continuous phase, depending on the amphiphile concentration. Simulations also
      reveal the importance of a strong adsorption of particles at the liquid interface
      to prevent their depletion from the droplet surface when another droplet
      approaches. Strongly adsorbed particles remain immobile on the droplet surface,
      generating an effective steric barrier against droplet coalescence. These
      findings provide new insights into the early dynamics and mechanisms of
      stabilization of emulsions using particles and amphiphilic molecules.

PMID- 29172535
TI  - Dewetting-Induced Photoluminescent Enhancement of Poly(lauryl
      methacrylate)/Quantum Dot Thin Films.
AB  - A new method for enhancing photoluminescence from quantum dot (QD)/polymer
      nanocomposite films is proposed. Poly(lauryl methacrylate) (PLMA) thin films
      containing embedded QDs are intentionally allowed to undergo dewetting on
      substrates by exposure to a nonsolvent vapor. After controlled dewetting, films
      exhibited typical dewetting morphologies with increased amounts of scattering
      that served to outcouple photoluminescence from the film and reduce internal
      light propagation within the film. Up to a 5-fold enhancement of the film
      emission was achieved depending on material factors such as the initial film
      thickness and QD concentration within the film. An increase in initial film
      thickness was shown to increase the dewetted maximum feature size and its
      characteristic length until a critical thickness was reached where dewetting
      became inhibited. A unique light exposure-based photopatterning method is also
      presented for the creation of high contrast emissive patterns as guided by
      spatially controlled dewetting.

PMID- 29172536
TI  - Role of Torsion-Vibration Coupling in the Overtone Spectrum and Vibrationally
      Mediated Photochemistry of CH3OOH and HOOH.
AB  - The yield of vibrationally excited OH fragments resulting from the vibrationally
      mediated photodissociation of methyl hydroperoxide (CH3OOH) excited in the
      vicinity of its 2nuOH and 3nuOH stretching overtones is compared with that
      resulting from excitation of the molecule to states with three quanta in the CH
      stretches and to the state with two quanta in the OH stretch and one in the OOH
      bend (2nuOH + nuOOH). We find that the OH fragment vibrational state distribution
      depends strongly on the vibrational state of CH3OOH prior to photodissociation.
      Specifically, dissociation from the CH stretch overtones and the stretch/bend
      combination band involving the OH stretch and OOH bend produced significantly
      less vibrationally excited OH fragments compared to that produced following
      excitation of CH3OOH to an overtone in the OH stretch. While the absence of
      vibrationally excited OH photoproducts following excitation of the CH overtone is
      not surprising, the lack of vibrationally excited OH following excitation to the
      2nuOH+nuOOH combination band is unexpected given that photodissociation following
      excitation to the lower-energy 2nuOH state produces OH products in v = 1 as well
      as in its ground state. This trend persists even when the electronic
      photodissociation wavelength is changed from 532 to 355 nm and thus suggests that
      the observed disparity arises from differences in the nature of the initially
      populated vibrational states. This lack of vibrationally excited OH products
      likely reflects the enhanced intramolecular vibrational energy redistribution
      associated with the stretch/bend combination level compared to the pure OH
      stretch overtone. Consistent with this hypothesis, photodissociation from the
      stretch/bend combination level of the smaller HOOH molecule produces more
      vibrationally excited OH fragments compared to that resulting from the
      corresponding state of CH3OOH. These results are investigated using second-order
      vibrational perturbation theory based on an internal coordinate representation of
      the normal modes. Consistent with the observations, the first-order correction to
      the wave function shows stronger coupling of the 2nuOH+nuOOH state to states with
      torsion excitation compared to the other bands considered in this study.

PMID- 29172537
TI  - Few-Electron Ultrastrong Light-Matter Coupling at 300 GHz with Nanogap Hybrid LC
      Microcavities.
AB  - Ultrastrong light-matter coupling allows the exploration of new states of matter
      through the interaction of strong vacuum fields with huge electronic dipoles. By
      using hybrid dipole antenna-split ring resonator-based cavities with extremely
      small effective mode volumes Veff/lambda03 ? 6 * 10-10 and surfaces Seff/lambda02
      ? 3.5 * 10-7, we probe the ultrastrong light-matter coupling at 300 GHz to less
      than 100 electrons located in the last occupied Landau level of a high mobility
      two-dimensional electron gas, measuring a normalized coupling ratio of
      OmegaR/omegac = 0.36. Effects of the extremely reduced cavity dimensions are
      observed as the light-matter coupled system is better described by an effective
      mass heavier than the uncoupled one. These results open the way to ultrastrong
      coupling at the single-electron level in two-dimensional electron systems.

PMID- 29172538
TI  - Real-Time Atomic Force Microscopy Imaging of Block Copolymer Directed Self
      Assembly.
AB  - The kinetics of directed self-assembly of symmetric PS-b-PMMA diblock copolymer
      on chemically patterned templates were measured during in situ thermal annealing.
      Although these chemical guide patterns lead to well-aligned, defect-free lamellar
      patterns at thermodynamic equilibrium, in practice, challenges remain in
      understanding and optimizing the kinetic evolution for technological
      applications. High-speed, environmentally controlled atomic force microscopy
      imaging was used to track pattern evolution on the time scale of individual
      microdomain connections in real space and time, allowing the direct visualization
      of defect healing mechanisms. When we apply this highly general technique to
      films on chemically patterned substrates, we find that pattern alignment is
      mediated by a metastable nonbulk morphology unique to these samples, referred to
      as the "stitch" morphology. We observe diverse and anisotropic mechanisms for the
      conversion from this morphology to equilibrium lamellar stripes. Directed self
      assembly on chemical templates is observed to follow exponential kinetics with an
      apparent energetic barrier of 360 +/- 80 kJ/mol from 210-230  degrees C, a
      significant enhancement when compared with ordering rates on unpatterned
      substrates. Ultimately, from local imaging, we find that the presence of a
      chemical guiding field causes morphological ordering and lamellar alignment to
      occur irreversibly.

PMID- 29172539
TI  - Proteome Comparisons between Hemolymph of Two Honeybee Strains (Apis mellifera
      ligustica) Reveal Divergent Molecular Basis in Driving Hemolymph Function and
      High Royal Jelly Secretion.
AB  - Hemolymph is vital for the immunity of honeybees and offers a way to investigate
      their physiological status. To gain novel insight into the functionality and
      molecular details of the hemolymph in driving increased Royal Jelly (RJ)
      production, we characterized and compared hemolymph proteomes across the larval
      and adult ages of Italian bees (ITbs) and Royal Jelly bees (RJbs), a stock
      selected from ITbs for increasing RJ output. Unprecedented in-depth proteome was
      attained with the identification of 3394 hemolymph proteins in both bee lines.
      The changes in proteome support the general function of hemolymph to drive
      development and immunity across different ages. However, age-specific proteome
      settings have adapted to prime the distinct physiology for larvae and adult bees.
      In larvae, the proteome is thought to drive temporal immunity, rapid
      organogenesis, and reorganization of larval structures. In adults, the proteome
      plays key roles in prompting tissue development and immune defense in newly
      emerged bees, in gland maturity in nurse bees, and in carbohydrate energy
      production in forager bees. Between larval and adult samples of the same age,
      RJbs and ITbs have tailored distinct hemolymph proteome programs to drive their
      physiology. In particular, in day 4 larvae and nurse bees, a large number of
      highly abundant proteins are enriched in protein synthesis and energy metabolism
      in RJbs. This implies that they have adapted their proteome to initiate different
      developmental trajectories and high RJ secretion in response to selection for
      enhanced RJ production. Our hitherto unexplored in-depth proteome coverage
      provides novel insight into molecular details that drive hemolymph function and
      high RJ production by RJbs.

PMID- 29172540
TI  - Discovery of a Small-Molecule Bromodomain-Containing Protein 4 (BRD4) Inhibitor
      That Induces AMP-Activated Protein Kinase-Modulated Autophagy-Associated Cell
      Death in Breast Cancer.
AB  - Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that
      several autophagy-related proteins such as AMP-activated protein kinase (AMPK)
      were remarkably downregulated in breast cancer. Combined with
      coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK.
      After analyses of the pharmacophore and WPF interaction optimization, we designed
      a small-molecule inhibitor of BRD4, 9f (FL-411) which was validated by cocrystal
      structure with BD1 of BRD4. Subsequently, 9f was discovered to induce ATG5
      dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction
      and thus activating AMPK-mTOR-ULK1-modulated autophagic pathway in breast cancer
      cells. Interestingly, the iTRAQ-based proteomics analyses revealed that 9f
      induced ACD pathways involved in HMGB1, VDAC1/2, and eEF2. Moreover, 9f displayed
      a therapeutic potential on both breast cancer xenograft mouse and zebrafish
      models. Together, these results demonstrate that a novel small-molecule inhibitor
      of BRD4 induces BRD4-AMPK-modulated ACD in breast cancer, which may provide a
      candidate drug for future cancer therapy.

PMID- 29172541
TI  - Parallel-Coupled Quantum Dots in InAs Nanowires.
AB  - We use crystal-phase tuning during epitaxial growth of InAs nanowires to create
      quantum dots with very strong confinement. A set of gate electrodes are used to
      reproducibly split the quantum dots into even smaller pairs for which we can
      control the populations down to the last electron. The double quantum dots, which
      are parallel-coupled to source and drain, show clear and stable odd-even level
      pairing due to spin degeneracy and the strong confinement. The combination of
      hard-wall barriers to source and drain, shallow interdot tunnel barriers, and
      very high single-particle excitation energies allow an order of magnitude tuning
      of the strength for the first intramolecular bond. We show examples for nanowires
      with different facet orientations, and suggest possible mechanisms behind the
      reproducible double-dot formation.

PMID- 29172542
TI  - Enzyme and Chemical Assisted N-Terminal Blocked Peptides Analysis, ENCHANT, as a
      Selective Proteomics Approach Complementary to Conventional Shotgun Approach.
AB  - Shotgun (bottom-up) approach has been widely applied in large-scale proteomics
      studies. The inherent shortages of shotgun approach lie in that the generated
      peptides often overwhelm the analytical capacity of current LC-MS/MS systems and
      that high-abundance proteins often hamper the identification of low-abundance
      proteins when analyzing complex samples. To reduce the sample complexity and
      relieve the problems caused by abundant proteins, herein we introduce a modified
      selective proteomics approach, termed ENCHANT, for enzyme and chemical assisted N
      terminal blocked peptides analysis. Modified from our previous Nalpha-acetylome
      approach, ENCHANT aims to analyze three kinds of peptides, acetylated protein N
      termini, N-terminal glutamine and N-terminal cysteine containing peptides.
      Application of ENCHANT to HeLa cells allowed to identify 3375 proteins, 19.6%
      more than that by conventional shotgun approach. More importantly, ENCHANT
      demonstrated an excellent complementarity to conventional shotgun approach with
      the overlap of 34.5%. In terms of quantification using data independent
      acquisition (DIA) technology, ENCHANT quantified 23.9% more proteins than
      conventional shotgun approach with the overlap of 27.6%. Therefore, our results
      strongly suggest that ENCHANT is a promising selective proteomics approach, which
      is complementary to conventional shotgun approach in both qualitative and
      quantitative proteomics studies. Data are available via ProteomeXchange with
      identifier PXD007863.

PMID- 29172543
TI  - Large Proximity-Induced Spin Lifetime Anisotropy in Transition-Metal
      Dichalcogenide/Graphene Heterostructures.
AB  - Van der Waals heterostructures have become a paradigm for designing new materials
      and devices in which specific functionalities can be tailored by combining the
      properties of the individual 2D layers. A single layer of transition-metal
      dichalcogenide (TMD) is an excellent complement to graphene (Gr) because the high
      quality of charge and spin transport in Gr is enriched with the large spin-orbit
      coupling of the TMD via the proximity effect. The controllable spin-valley
      coupling makes these heterostructures particularly attractive for spintronic and
      opto-valleytronic applications. In this work, we study spin precession in a
      monolayer MoSe2/Gr heterostructure and observe an unconventional, dramatic
      modulation of the spin signal, showing 1 order of magnitude longer lifetime of
      out-of-plane spins compared to that of in-plane spins (tau? ~ 40 ps and tau? ~
      3.5 ps). This demonstration of a large spin lifetime anisotropy in TMD/Gr
      heterostructures, is a direct evidence of induced spin-valley coupling in Gr and
      provides an accessible route for manipulation of spin dynamics in Gr, interfaced
      with TMDs.

PMID- 29172544
TI  - A Substrate-Selective Enzyme-Catalysis Assembly Strategy for Oligopeptide
      Hydrogel-Assisted Combinatorial Protein Delivery.
AB  - Oligopeptide hydrogels for localized protein delivery have considerable potential
      to reduce systemic side effects but maximize therapeutic efficacy. Although
      enzyme catalysis to induce formation of oligopeptide hydrogels has the merits of
      unique regio- and enantioselectivity and mild reaction conditions, it may cause
      the impairment of function and activity of the encapsulated proteins by
      proteolytic degradation during gelation. Here we report a novel enzyme-catalysis
      strategy for self-assembly of oligopeptide hydrogels using an engineered protease
      nanocapsule with tunable substrate selectivity. The protease-encapsulated
      nanocapsule shielded the degradation activity of protease on the laden proteins
      due to the steric hindrance by the polymeric shell weaved around the protease,
      whereas the small-molecular precursors were easier to penetrate across the
      polymeric network and access the catalytic pocket of the protease to convert to
      the gelators for self-assembling hydrogel. The resulting oligopeptide hydrogels
      supported a favorable loading capacity without inactivation of both an
      antiangiogenic protein, hirudin and an apoptosis-inducing cytokine, TRAIL as
      model proteins. The hirudin and TRAIL coloaded oligopeptide hydrogel for
      combination cancer treatment showed enhanced synergistic antitumor effects both
      in vitro and in vivo.

PMID- 29172545
TI  - Sulfur Adatom and Vacancy Accelerate Charge Recombination in MoS2 but by
      Different Mechanisms: Time-Domain Ab Initio Analysis.
AB  - Two-dimensional transition metal dichalcogenides (TMDs) have appeared on the
      horizon of materials science and solid-state physics due to their unique
      properties and diverse applications. TMD performance depends strongly on material
      quality and defect morphology. Calculations predict that sulfur adatom and
      vacancy are among the most energetically favorable defects in MoS2 with vacancies
      frequently observed during chemical vapor deposition. By performing ab initio
      quantum dynamics calculations we demonstrate that both adatom and vacancy
      accelerate nonradiative charge carrier recombination but this happens through
      different mechanisms. Surprisingly, holes never significantly populate the
      shallow trap state created by the sulfur adatom because the trap is strongly
      localized and decoupled from free charges. Charge recombination bypasses the hole
      trap. Instead, it occurs directly between free electron and hole. The
      recombination is faster than in pristine MoS2 because the adatom strongly
      perturbs the MoS2 layer, breaks its symmetry, and allows more phonon modes to
      couple to the electronic subsystem. In contrast, the sulfur vacancy accelerates
      charge recombination by the traditional mechanism involving charge trapping,
      followed by recombination. This is because the hole and electron traps created by
      the vacancy are much less localized than the hole trap created by the adatom.
      Because the sulfur adatom accelerates charge recombination by a factor of 7.9,
      compared to 1.7 due to vacancy, sulfur adatoms should be strongly avoided. The
      generated insights highlight the diverse behavior of different types of defects,
      reveal unexpected features, and provide the mechanistic understanding of charge
      dynamics needed for tailoring TMD properties and building high-performance
      devices.

PMID- 29172546
TI  - Crossover-Annulation/Oxygenation Approach to Functionalized Phenanthridines by
      Palladium-Copper Relay Catalysis.
AB  - A tandem crossover-annulation and oxygenation process of conjugated enediyne
      acids and ortho-alkynylanilines was achieved by palladium-copper relay catalysis
      under an oxygen atmosphere, giving access to the three-component assembly of 9
      acylphenanthridine compounds.

PMID- 29172547
TI  - Cu-Catalyzed Enantioselective Boron Addition to N-Heteroaryl-Substituted Alkenes.
AB  - Catalytic enantioselective Cu-B(pin) (pin = pinacolato) addition to N-heteroaryl
      substituted alkenes followed by protonation promoted by phosphine-Cu complexes is
      presented. The resulting alkylboron products that contain a N-heteroaryl moiety
      are afforded in up to 97% yield and 99:1 enantiomeric ratio. The highly versatile
      C-B(pin) bond can be converted to a range of useful functional groups, delivering
      a variety of enantiomerically enriched building blocks that are otherwise
      difficult to access. The utility of this method is further demonstrated by
      application to a fragment synthesis of biologically active molecule U-75302.
      Preliminary mechanistic studies revealed that the adjacent N atom of the
      heterocycles plays a unique role in high reactivity and enantioselectivity.

PMID- 29172548
TI  - Synthesis of Poly-Ubiquitin Chains Using a Bifunctional Ubiquitin Monomer.
AB  - An optimized large scale and highly reproducible route to orthogonally protected
      gamma-thiolysine is reported. Its utility in the synthesis of bifunctional
      ubiquitin monomers is demonstrated. These ubiquitin synthons are employed in
      polymerization reactions giving access to synthetic poly-ubiquitin chains of
      defined linkage.

PMID- 29172549
TI  - Proteomic Characterization of Dermal Interstitial Fluid Extracted Using a Novel
      Microneedle-Assisted Technique.
AB  - As wearable fitness devices have gained commercial acceptance, interest in real
      time monitoring of an individual's physiological status using noninvasive
      techniques has grown. Microneedles have been proposed as a minimally invasive
      technique for sampling the dermal interstitial fluid (ISF) for clinical
      monitoring and diagnosis, but little is known about its composition. In this
      study, a novel microneedle array was used to collect dermal ISF from three
      healthy human donors and compared with matching serum and plasma samples. Using a
      shotgun quantitative proteomic approach, 407 proteins were quantified with at
      least one unique peptide, and of those, 135 proteins were differently expressed
      at least 2-fold. Collectively, these proteins tended to originate from the
      cytoplasm, membrane bound vesicles, and extracellular vesicular exosomes.
      Proteomic analysis confirmed previously published work that indicates that ISF is
      highly similar to both plasma and serum. In this study, less than one percent of
      proteins were uniquely identified in ISF. Taken together, ISF could serve as a
      minimally invasive alternative for blood-derived fluids with potential for real
      time monitoring applications.

PMID- 29172550
TI  - Surface Complexed ZnO Quantum Dot for White Light Emission with Controllable
      Chromaticity and Color Temperature.
AB  - We report the formation of blue emitting Zn(MSA)2 complex on the surface of a
      yellow emitting ZnO quantum dot (Qdot)-out of a complexation reaction between N
      methylsalicylaldimine (MSA) and ZnO Qdot. This led to formation of a highly
      luminescent, photostable, single-component nanocomposite that emits bright
      natural white light, with (i) chromaticities of (0.31, 0.38) and (0.31, 0.36),
      (ii) color rendering indices (CRI) of 74 and 82, and (iii) correlated color
      temperatures (CCT) of 6505 and 6517 K in their solution and solid phases,
      respectively. Importantly, the control over the chromaticity and CCT-depending
      upon the degree of complexation-makes the reported nanocomposite a potential new
      advanced material in fabricating cost-effective single-component white light
      emitting devices (WLED) of choice and design in the near future.

PMID- 29172551
TI  - Synthesis of Excitation Independent Highly Luminescent Graphene Quantum Dots
      through Perchloric Acid Oxidation.
AB  - We demonstrate a facile liquid phase exfoliation method by only using perchloric
      acid to synthesize graphene quantum dots (GQDs) having excitation independent
      strong emission with a quantum yield of about 14%. The proposed simplified
      synthesis strategy can help in overcoming the limitations of existing aqueous
      routes which produce GQDs with excitation dependent emission and of low quantum
      efficiency. Photoluminescence (PL) properties of GQDs have been studied in detail
      to understand the origin of emission. As-synthesized GQDs show excitation
      independent photoluminesce (PL) which suggests that the synthesized materials do
      not have any significant defects. Spectral analysis suggests that the PL emission
      of the well-defined GQDs originates mainly from the peripheral functional groups
      conjugated with carbon backbone planes. We also demonstrate a relatively longer
      PL lifetime (average lifetime of about 10 ns) of the synthesized GQDs determined
      by time correlated single photon counting (TCSPC) measurement and this high
      lifetime suggests that the synthesized GQDs may be suitable for biomacromolecular
      probing. In addition, as-synthesized GQDs interestingly show delayed fluorescence
      and steady state anisotropy, which make the material an appropriate candidate for
      application in sensing and bioimaging of cells and organisms.

PMID- 29172552
TI  - TBAI/TBHP-Mediated Cascade Cyclization toward Sulfonylated Indeno[1,2
      c]quinolines.
AB  - Treatment of ortho-amino-substituted aryldiyne derivatives with sulfonyl
      hydrazides in the presence of tetrabutylammonium iodide (TBAI) and tert-butyl
      hydroperoxide (TBHP) led to a cascade cyclization reaction to yield sulfonylated
      indeno[1,2-c]quinolines in moderate to good yields. The features of the
      methodology include metal-free reaction, the ease of reagent handling, and a
      broad functional group tolerance.

PMID- 29172553
TI  - General Method for the Suzuki-Miyaura Cross-Coupling of Primary Amide-Derived
      Electrophiles Enabled by [Pd(NHC)(cin)Cl] at Room Temperature.
AB  - A general, highly selective method for the room temperature Suzuki-Miyaura cross
      coupling of commonly encountered primary benzamides is reported. A combination of
      site-selective N,N-di-Boc-activation (tert-butoxycarbonyl activation) of the
      amide nitrogen with practical air- and moisture-stable, well-defined, and highly
      reactive [Pd(NHC)(cin)Cl] (NHC = N-heterocyclic carbene; cin = cinnamyl) provides
      a highly effective route to biaryl ketones from primary amides in high yields.
      For the first time, a TON of >1000 has been achieved in amide acyl cross
      coupling.

PMID- 29172554
TI  - Interfacing five-factor model and triarchic conceptualizations of psychopathy.
AB  - The lexically based five-factor model (FFM) of personality has been a highly
      influential research framework for characterizing clinical-psychological
      conditions, including psychopathy, in lexical-trait terms. An alternative trait
      descriptive framework, the triarchic model was formulated to characterize
      psychopathy in neurobehavioral-trait terms, in order to facilitate linkages with
      variables in the domain of neurobiology. The current study used data from a mixed
      gender sample (N = 769; M age = 19.3) to establish an interface between the FFM
      and triarchic frameworks by identifying subsets of items from a widely used five
      factor personality inventory, the NEO Personality Inventory-Revised (NEO-PI-R),
      that effectively index the dimensional constructs of the triarchic model
      (boldness, meanness, and disinhibition). A consensus rating and psychometric
      refinement approach was used to select NEO-PI-R items for assessing each
      triarchic dimension, and the resulting NEO-Tri item-sets ("scales") were
      evaluated in relation to criteria including other scale measures of the triarchic
      constructs, reported antisocial behavior and drug/alcohol use, and an FFM
      generated omnibus psychopathy measure, the Psychopathy Resemblance Index. The NEO
      Tri scales were also evaluated for effectiveness as indicators of latent
      triarchic dimensions within a confirmatory factor analysis anchored by previously
      validated triarchic scale measures. Results of this work have implications for
      clarifying how the triarchic model dimensions relate to normal-range personality
      traits and FFM-based conceptions of psychopathy, and provide a foundation for
      further examining neurobiological correlates of the triarchic model dimensions
      using existing multidomain data-sets that include the NEO-PI-R. (PsycINFO
      Database Record

PMID- 29172555
TI  - Visiting Auschwitz: Evidence of secondary traumatization among high school
      students.
AB  - Secondary traumatic stress has been intensively studied among survivors'
      therapists, family members, and trauma researchers. We claim that people who are
      exposed to reminders of past traumatic experiences when visiting places of memory
      or museum exhibitions could also develop secondary trauma symptoms. Thus,
      scholars and practitioners must better understand how such places related to
      historical traumatization (e.g., Holocaust memorial sites) can affect the
      psychological well-being of visitors. The main aim of this quantitative
      longitudinal study was to assess the scale of secondary traumatization among
      visitors to such places. The study found that the syndrome of secondary traumatic
      stress was observed among 13.2% of high school visitors to the Auschwitz memorial
      museum. Longitudinal analysis revealed that empathic reactions to the visit in
      Auschwitz (e.g., a greater inclusion of victims into the self) were associated
      with higher levels of secondary traumatic stress levels 1 month after the visit.
      This study suggests that visits to places related to traumatic past events should
      be preceded by a more intense elaboration of Holocaust history and by proper
      psychological preparations. (PsycINFO Database Record

PMID- 29172556
TI  - Bullying and minorities in secondary school students in Thrace-Greece.
AB  - The aim of the present study is to examine probable heterogeneity in aggressive
      behaviors and peer victimization among ethnically diverse secondary schools in
      Thrace. It is a culturally diverse region in Northeastern Greece, which includes
      Greek Christians and a significant minority of Muslims and immigrants. The study
      population consisted of 572 school students (293 girls, 279 boys, Mage = 14.24),
      who completed the Revised Olweus Bully/Victim Questionnaire for Students-Senior
      and the Youth Self-Report. The percentage of students involved in bullying was
      34.7%. More specifically, we found that 24.7% of the students were bully victims,
      followed by 18.5% bully/victims, and 17.8% bullies. Peer victimization was 52%
      less frequent in schools with low proportion of minority students (low school
      minority density; adjusted odds ratio [AOR] = 0.48, p = .015) and 61% less
      frequent in schools with high minority density (AOR = 0.39, p = .010) as compared
      to schools with moderate minority density. Furthermore, bullying and
      bully/victims behaviors were at least 65% less frequent in schools with high
      density (bullying: AOR = 0.35, p = .016; bully/victim: AOR = 0.30, p = .027) as
      compared to schools with moderate density, while a similar tendency was also
      observed in low density areas. Findings from the current study have implications
      for research and practice. More specifically, our findings can contribute to the
      development of effective prevention policies and strategies. (PsycINFO Database
      Record

PMID- 29172557
TI  - Expanding the early and late starter model of criminal justice involvement for
      forensic mental health clients.
AB  - The early and late starter model provides one of the most enduring frameworks for
      understanding the developmental course and severity of violence and criminality
      among individuals with severe mental illness. We expanded the model to account
      for differences in the age of onset of criminal behavior and added a group with
      no prior contact with the justice or mental health systems. We sampled 1,800 men
      and women found Not Criminally Responsible on account of Mental Disorder in 3
      Canadian provinces. Using a retrospective file-based study, we explored
      differences in criminal, health, demographic, and social functioning
      characteristics, processing through the forensic psychiatric system and
      recidivism outcomes of 5 groups. We replicated prior research, finding more
      typical criminogenic needs among those with early onset crime. Those with crime
      onset after mental illness were more likely to show fewer criminogenic needs and
      to have better outcomes upon release than those who had crime onset during
      adulthood, before mental illness. Individuals with no prior contact with mental
      health or criminal justice had higher functioning prior to their crime and had a
      lower risk of reoffending. Given little information is needed to identify the
      groups, computing the distribution of these groups within forensic mental health
      services or across services can provide estimates of potential intensity or
      duration of services that might be needed. This study suggests that
      distinguishing subgroups of forensic clients based on the sequence of onset of
      mental illness and criminal behavior and on the age of onset of criminal behavior
      may be useful to identify criminogenic needs and predict outcomes upon release.
      This updated framework can be useful for planning organization of services,
      understanding case mix, as well as patient flow in forensic services and flow of
      mentally disordered offenders in correctional services. (PsycINFO Database Record

PMID- 29172558
TI  - Childhood risk factors associated with adolescent gun carrying among Black and
      White males: An examination of self-protection, social influence, and antisocial
      propensity explanations.
AB  - Adolescent gun violence is a serious public health issue that disproportionately
      affects young Black males. Although it has been postulated that differential
      exposure to childhood risk factors might account for racial differences in
      adolescent gun carrying, no longitudinal studies have directly examined this
      issue. We examined whether childhood risk factors indexing neighborhood crime,
      peer delinquency, and conduct problems predicted the initiation of adolescent gun
      carrying among a community sample of Black and White boys. Analyses then examined
      whether racial differences in risk factors accounted for racial differences in
      gun carrying. Data came from a sample of 485 Black and White boys who were
      repeatedly assessed from 2nd grade until age 18. Multi-informant data collected
      across the first 3 years of the study were used to assess neighborhood crime,
      peer delinquency, and conduct problems. Illegal gun carrying was assessed
      annually from 5th grade through age 18. Growth curve analyses indicated that
      children with higher initial levels of conduct problems and delinquent peer
      involvement, as well as those who increased in conduct problems across childhood,
      were more likely to carry a gun prior to age 18. Black boys were also more likely
      to carry guns than Whites. Racial differences were greatly reduced, but not
      eliminated, after controlling for initial levels of conduct problems and
      delinquent peer involvement. Findings suggest that early prevention programs
      designed to reduce adolescent gun violence (including racial disparities in gun
      violence) should target boys with severe conduct problems and those who affiliate
      with delinquent peers during elementary school. (PsycINFO Database Record

PMID- 29172559
TI  - Quantification of virtue in late Medieval Europe.
AB  - Fourteenth century Europe saw a growing interest in quantification. This interest
      has been well studied by historians of physical sciences, but medieval scholars
      were also interested in the quantification of psychological qualities. In
      general, the quantification issues addressed by medieval scholars were
      theoretical, even (by our standards) mathematical, rather than those of practical
      measurement. There was recognition that the seriousness of a sin and the penance
      laid down for it should be proportionate. A number of late medieval scholars were
      interested in the quantification of caritas, a Latin word that is translatable as
      charity or loving benevolence. The scholastic interest linked to the practical
      issue of how caritas might become habitual through the repeated performance of
      virtuous acts. Gregory of Rimini's treatment of caritas in his commentary on
      Peter Lombard's Sentences illustrates how one medieval scholar related the
      quantification of virtue to the quantification of physical qualities such as
      temperature and luminescence. (PsycINFO Database Record

PMID- 29172560
TI  - The testing effect in a social setting: Does retrieval practice benefit a
      listener?
AB  - Retrieval practice boosts retention relative to other study strategies like
      restudying, a finding known as the testing effect. In 3 experiments, the authors
      investigated testing in social contexts. Subjects participated in pairs and
      engaged in restudy and retrieval practice of vocabulary pairs. During retrieval
      practice, 1 subject acted as speaker (overt practice); the other subject listened
      and monitored the speaker's responses (covert practice). All experiments showed
      testing effects, with overt practice by speakers enhancing recall relative to
      restudy after a 2-day delay. In Experiments 1 and 2, covert practice by listeners
      did not benefit recall as much as overt practice. Only in Experiment 3, when
      listeners were asked to monitor their own covert retrieval (instead of the
      speaker's overt retrieval), did both types of practice convey similar benefits.
      The results indicate that memory retrieval is not necessarily as beneficial for
      listeners as for speakers. The practical implication is that the practice of
      teachers asking questions in class will not yield a positive effect unless
      special measures are taken to insure students' effortful covert retrieval.
      (PsycINFO Database Record

PMID- 29172561
TI  - Service usage typologies in a clinical sample of trauma-exposed adolescents: A
      latent class analysis.
AB  - OBJECTIVE: The purpose of this study is to describe typologies of service
      utilization among trauma-exposed, treatment-seeking adolescents and to examine
      associations between trauma history, trauma-related symptoms, demographics, and
      service utilization. METHOD: Latent class analysis was used to derive a service
      utilization typologies based on 10 service variables using a sample of 3,081
      trauma-exposed adolescents ages 12 to 16 from the National Child Traumatic Stress
      Network Core Dataset. Services used 30 days prior to the initial assessment from
      5 sectors were examined (health care, mental health, school, social services, and
      juvenile justice). RESULTS: A 5-class model was selected based on statistical fit
      indices and substantive evaluation of classes: (a) High intensity/multisystem,
      9.5%; (b) Justice-involved, 7.2%; (c) Low intensity/multisystem, 19.9%; (d)
      Social service and mental health, 19.9%; and (e) Low service usage/reference,
      43.5%. The classes could be differentiated based on cumulative trauma,
      maltreatment history, PTSD, externalizing and internalizing symptoms, and age,
      gender, race/ethnicity and place of residence. CONCLUSIONS: This study provides
      new evidence about patterns of service utilization by trauma exposed, treatment
      seeking adolescents. Most of these adolescents appear to be involved with at
      least 2 service systems prior to seeking trauma treatment. Higher cumulative
      exposure to multiple types of trauma was associated with greater service
      utilization intensity and complexity, but trauma symptomatology was not.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29172562
TI  - Association between perceptions of military service and mental health problems in
      a nationally representative sample of United States military veterans.
AB  - OBJECTIVE: In this study, we examined the prevalence of positive and negative
      perceptions of military service, associations between these perceptions and other
      demographic and military-related factors, and the extent to which endorsement of
      positive and negative perceptions of military service are associated with current
      mental health problems among United States veterans. METHOD: We analyzed data
      from the National Health and Resilience in Veterans Study (NHRVS), a nationally
      representative survey of 1,484 United States military veterans, 564 of which
      reported combat exposure. We assessed perceptions of the effects of military
      service using a scale developed by Elder and Clipp (1989). RESULTS: Results
      showed that desirable effects of service (53.6-86.5%) were more frequently
      endorsed than undesirable effects (9.5%-48.1%), and that combat-exposed veterans
      (11.5%-59.7%) were more likely to endorse undesirable effects of service than
      veterans without combat exposure (4.0%-40.7%). We also found that undesirable
      effects of service predicted significantly higher odds of probable current mental
      health disorders (OR = 1.08, 95% CI [1.04, 1.12]), and current suicidal ideation
      (OR = 1.09, 95% CI [1.05, 1.13]), even after conservative adjustment for possible
      confounding variables. Desirable effects of service predicted significantly lower
      odds of current suicidal ideation (OR = 0.96, 95% CI [0.93, 0.99]). CONCLUSION:
      Taken together, results of this study suggest that perceptions of military
      service are associated with suicidal ideation and other mental health conditions.
      In addition, assessing veterans' perceptions of their service could be used as a
      method to identify possible at-risk veterans who may benefit from mental health
      services and resources. (PsycINFO Database Record

PMID- 29172563
TI  - Examining the impact of behavioral health encounter dose and frequency on
      posttraumatic stress symptoms among active duty service members.
AB  - OBJECTIVE: Several factors may influence the standardized delivery and frequency
      of behavioral health encounters for posttraumatic stress disorder (PTSD) in
      active duty military settings, potentially impacting the effectiveness of care.
      This retrospective analysis evaluated the course of treatment among 884 active
      duty Army service members in routine outpatient care. METHOD: Patients were
      included in the analysis based on a screening score of 50 or higher on the PTSD
      Checklist (PCL-C) at intake. Patients subsequently completed the PCL-C at
      periodic intervals during behavioral health encounters. A multilevel model
      predicting PCL-C score was constructed with the number of encounters and days
      between encounters as predictor variables, controlling for intake PCL-C scores.
      RESULTS: A higher number of total encounters during the entire study period
      predicted lower scores on the PCL-C. Quadratic effects showed that encounter
      frequency of less than 3 weeks and treatment during the first 8 encounters was
      associated with lower symptoms. A curvilinear effect showed that long breaks in
      care are associated with greater PTSD symptoms, but also that very-frequent care
      (e.g., twice weekly) would be associated with greater symptoms. CONCLUSION: These
      results suggest the need to carefully monitor the frequency and overall dose of
      behavioral health encounters for PTSD among active duty military patients,
      suggesting that the greatest treatment gains occur early in treatment and that
      there is a need for idiographic treatment planning that addresses both the needs
      of the patient and the mission needs of the military command. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 29172565
TI  - There's no team in I: How observers perceive individual creativity in a team
      setting.
AB  - Creativity is highly valued in organizations as an important source of
      innovation. As most creative projects require the efforts of groups of
      individuals working together, it is important to understand how creativity is
      perceived for team products, including how observers attribute creative ability
      to focal actors who worked as part of a creative team. Evidence from three
      experiments suggests that observers commit the fundamental attribution error
      systematically discounting the contribution of the group when assessing the
      creative ability of a single group representative, particularly when the group
      itself is not visually salient. In a pilot study, we found that, in the context
      of the design team at Apple, a target group member visually depicted alone is
      perceived to have greater personal creative ability than when he is visually
      depicted with his team. In Study 1, using a sample of managers, we conceptually
      replicated this finding and further observed that, when shown alone, a target
      member of a group that produced a creative product is perceived to be as creative
      as an individual described as working alone on the same output. In Study 2, we
      replicated the findings of Study 1 and also observed that a target group member
      depicted alone, rather than with his team, is also attributed less creative
      ability for uncreative group output. Findings are discussed in light of how
      overattribution of individual creative ability can harm organizations in the long
      run. (PsycINFO Database Record

PMID- 29172564
TI  - Meta-analysis of action video game impact on perceptual, attentional, and
      cognitive skills.
AB  - The ubiquity of video games in today's society has led to significant interest in
      their impact on the brain and behavior and in the possibility of harnessing games
      for good. The present meta-analyses focus on one specific game genre that has
      been of particular interest to the scientific community-action video games, and
      cover the period 2000-2015. To assess the long-lasting impact of action video
      game play on various domains of cognition, we first consider cross-sectional
      studies that inform us about the cognitive profile of habitual action video game
      players, and document a positive average effect of about half a standard
      deviation (g = 0.55). We then turn to long-term intervention studies that inform
      us about the possibility of causally inducing changes in cognition via playing
      action video games, and show a smaller average effect of a third of a standard
      deviation (g = 0.34). Because only intervention studies using other commercially
      available video game genres as controls were included, this latter result
      highlights the fact that not all games equally impact cognition. Moderator
      analyses indicated that action video game play robustly enhances the domains of
      top-down attention and spatial cognition, with encouraging signs for perception.
      Publication bias remains, however, a threat with average effects in the published
      literature estimated to be 30% larger than in the full literature. As a result,
      we encourage the field to conduct larger cohort studies and more intervention
      studies, especially those with more than 30 hours of training. (PsycINFO Database
      Record

PMID- 29172566
TI  - An integrated model of academic self-concept development: Academic self-concept,
      grades, test scores, and tracking over 6 years.
AB  - Our newly proposed integrated academic self-concept model integrates 3 major
      theories of academic self-concept formation and developmental perspectives into a
      unified conceptual and methodological framework. Relations among math self
      concept (MSC), school grades, test scores, and school-level contextual effects
      over 6 years, from the end of primary school through the first 5 years of
      secondary school (a representative sample of 3,370 German students, 42 secondary
      schools, 50% male, M age at grade 5 = 11.75) support the (1) internal/external
      frame of reference model: Math school grades had positive effects on MSC, but the
      effects of German grades were negative; (2) reciprocal effects (longitudinal
      panel) model: MSC was predictive of and predicted by math test scores and school
      grades; (3) big-fish-little-pond effect: The effects on MSC were negative for
      school-average achievement based on 4 indicators (primary school grades in math
      and German, school-track prior to the start of secondary school, math test scores
      in the first year of secondary school). Results for all 3 theoretical models were
      consistent across the 5 secondary school years: This supports the prediction of
      developmental equilibrium. This integration highlights the robustness of support
      over the potentially volatile early to middle adolescent period; the
      interconnectedness and complementarity of 3 ASC models; their counterbalancing
      strengths and weaknesses; and new theoretical, developmental, and substantive
      implications at their intersections. (PsycINFO Database Record

PMID- 29172567
TI  - Parent praise to toddlers predicts fourth grade academic achievement via
      children's incremental mindsets.
AB  - In a previous study, parent-child praise was observed in natural interactions at
      home when children were 1, 2, and 3 years of age. Children who received a
      relatively high proportion of process praise (e.g., praise for effort and
      strategies) showed stronger incremental motivational frameworks, including a
      belief that intelligence can be developed and a greater desire for challenge,
      when they were in 2nd or 3rd grade (Gunderson et al., 2013). The current study
      examines these same children's (n = 53) academic achievement 1 to 2 years later,
      in 4th grade. Results provide the first evidence that process praise to toddlers
      predicts children's academic achievement (in math and reading comprehension) 7
      years later, in elementary school, via their incremental motivational frameworks.
      Further analysis of these motivational frameworks shows that process praise had
      its effect on fourth grade achievement through children's trait beliefs (e.g.,
      believing that intelligence is fixed vs. malleable), rather than through their
      learning goals (e.g., preference for easy vs. challenging tasks). Implications
      for the socialization of motivation are discussed. (PsycINFO Database Record

PMID- 29172568
TI  - Tone series and the nature of working memory capacity development.
AB  - Recent advances in understanding visual working memory, the limited information
      held in mind for use in ongoing processing, are extended here to examine auditory
      working memory development. Research with arrays of visual objects has shown how
      to distinguish the capacity, in terms of the number of objects retained, from the
      precision of the object representations. We adapt the technique to sequences of
      nonmusical tones, in an investigation including children (6-13 years, N = 84) and
      adults (26-50 years, N = 31). For each series of 1 to 4 tones, the participant
      responded by using an 80-choice scale to try to reproduce the tone at a queried
      serial position. Despite the much longer-lasting usefulness of sensory memory for
      tones compared with visual objects, the observed tone capacity was similar to
      previous findings for visual capacity. The results also constrain theories of
      childhood working memory development, indicating increases with age in both the
      capacity and the precision of the tone representations, similar to the visual
      studies, rather than age differences in time-based memory decay. The findings,
      including patterns of correlations between capacity, precision, and some
      auxiliary tasks and questionnaires, establish capacity and precision as
      dissociable processes and place important constraints on various hypotheses of
      working memory development. (PsycINFO Database Record

PMID- 29172569
TI  - The emergence of the empirical stance: Children's testing of counterintuitive
      claims.
AB  - Although children often believe an adult's claims, they may have opportunities to
      check these claims by gathering relevant empirical evidence themselves. Here, we
      examine whether children seize such opportunities, especially when the claim is
      counterintuitive. Chinese preschool and elementary schoolchildren were presented
      with five different-sized Russian dolls and asked to indicate the heaviest doll.
      Almost all children selected the biggest doll. Half of the children then heard a
      false, counterintuitive claim (i.e., smallest = heaviest). The remaining children
      heard a claim confirming their initial intuition (i.e., biggest = heaviest).
      Children in both age groups typically endorsed the experimenter's claim even when
      it was counterintuitive. However, during the experimenter's subsequent absence,
      elementary schoolchildren explored the dolls more if they had received
      counterintuitive rather than confirming testimony whereas preschool children
      rarely explored, no matter what testimony they had received. Thus, with
      increasing age, children seize opportunities to test counterintuitive claims.
      (PsycINFO Database Record

PMID- 29172570
TI  - Clarifying the relation of acculturative stress and anxiety/depressive symptoms:
      The role of anxiety sensitivity among Hispanic college students.
AB  - OBJECTIVES: Recent work has highlighted the link between acculturative stress and
      depression/anxiety symptoms among Hispanic young adults, but the nature of these
      relations is not well understood. The present study aimed to clarify the relation
      between acculturative stress and depression/anxiety symptoms by examining anxiety
      sensitivity, globally and via subfactors, as an explanatory variable. METHOD: A
      cross-sectional sample of 788 Hispanic college students (80.8% female; Mage =
      20.83 years, SD = 1.93) was recruited from a southwestern public university and
      completed an online self-report assessment battery. RESULTS: Acculturative stress
      exerted an indirect effect, via the global construct of anxiety sensitivity, on
      depression symptoms, suicidality, anxious arousal, and social anxiety symptoms.
      Follow-up simultaneous analytic models demonstrated indirect effects via the
      anxiety sensitivity subfactors that were pathognomonic with each of the specific
      affective outcomes. CONCLUSIONS: These findings suggest the utility of assessing
      and targeting anxiety sensitivity in the treatment of acculturative stress
      related depression/anxiety problems among Hispanic college students. (PsycINFO
      Database Record

PMID- 29172571
TI  - Processes underlying Mexican-origin adolescent mothers' BMI.
AB  - OBJECTIVE: To examine potential mediating and moderating factors in the
      longitudinal association between contextual stressors (economic hardship, ethnic
      discrimination) and subsequent engagement in risky behaviors and body mass index
      (BMI) of Mexican-origin adolescent mothers. METHOD: Participants were Mexican
      origin adolescent mothers (N = 204) who were recruited from community agencies
      and high schools in a Southwestern metropolitan area. Contextual stressors and
      risky behaviors were assessed 3 and 4 years postpartum. Adolescent mothers' BMI
      was assessed 5-years postpartum. Path analyses assessed moderated mediation with
      risky behaviors as a mediator of associations between contextual stressors and
      BMI, and family and friend support as moderators of the mediated pathways.
      RESULTS: At low levels of family support, economic hardship at 3-years postpartum
      positively predicted engagement in risky behaviors at 4-years postpartum, which
      in turn positively predicted BMI at 5-years postpartum. At high levels of family
      support, all relations were not significant. At low levels of friend support,
      ethnic discrimination at 3-years postpartum positively predicted engagement in
      risky behaviors at 4-years postpartum, which in turn positively predicted BMI at
      5-years postpartum. At high levels of friend support, all relations were not
      significant. CONCLUSIONS: Among adolescent mothers who receive low levels of
      family and friend support, engagement in risky behaviors may function as a
      mechanism through which contextual stressors are linked to adolescent mothers'
      BMI. Findings have implications for prevention efforts aimed at attenuating
      unhealthy weight status among Mexican-origin adolescent mothers by reducing
      engagement in risky behaviors and bolstering family and friend support. (PsycINFO
      Database Record

PMID- 29172572
TI  - A narrative approach to the role of others in ethnic identity formation.
AB  - OBJECTIVES: The aim of the present study was to explore the role of others in
      ethnic identity development. Three questions were asked: to what extent others
      are involved in these processes, what roles they play, and whether the roles
      differed between participant who identified with a majority, minority or mixed
      ethnic identity. METHOD: An exploratory, narrative approach was used, and written
      narratives were analyzed both qualitatively and quantitatively. The analytic
      sample consisted of 191 participants (78% female, Mage = 20.39, SD = 5.31), of
      which 64% identified as Swedish, 11% as another ethnicity, and 25% as
      Swedish/other ethnicity. RESULTS: Results showed that others were present in most
      of the ethnicity-defining experiences and most participants expressed a self
      defined ethnic identity. A thematic analysis of the role of others resulted in 6
      themes; others as contrast, as reference, raising awareness, accepting,
      ascribing, and denying. Most commonly, others functioned as a contrast and/or a
      reference point that the narrators could position themselves against.
      Participants with mixed majority/minority identities more often experienced that
      others ascribed or denied them their ethnic identities. CONCLUSIONS: The current
      findings lend empirical support for ethnic identity formation as an interactive
      process and for the role of others in these processes. A power imbalance was
      prevalent throughout the results, where the degree of looking and acting "Swedish
      enough" limited the power of choosing an identity. In multicultural societies,
      for people to have the power to define and have their ethnic identities accepted
      is a necessary condition for integration. (PsycINFO Database Record

PMID- 29172573
TI  - Profiles of culturally salient positive parenting practices among urban-residing
      Black Head Start families.
AB  - OBJECTIVES: To better understand within-group variability in positive parenting
      practices among low-income Black families, the present study, grounded in a
      multidimensional comparative framework, examined (a) patterns of positive
      parenting practices among U.S.-born African American parents and Black Caribbean
      immigrant parents and (b) the extent to which these patterns related to parents'
      daily family social support, parents' social sensitivities, and children's social
      emotional outcomes. METHOD: A person-oriented approach was employed with data
      from 524 African American and Black Caribbean immigrant parents (mothers,
      fathers, grandparents, aunts/uncles) of preschool-aged children in Head Start.
      RESULTS: Multistage hierarchical cluster analysis revealed that although the best
      solution for both ethnic groups was a 5-profile solution, the particular profiles
      that emerged across the 2 groups were distinct. Further, different parenting
      practices were salient among the 'high positive parenting' profiles and 'low
      positive parenting' for African Americans and Caribbean immigrants. In addition,
      demographic factors (education, gender, and marital status) differentially
      related to patterns of positive parenting across the 2 ethnic groups, and these
      patterns of parenting were associated with children's social emotional
      development and parenting resources in meaningful ways. CONCLUSIONS: Findings
      underscore the importance of conducting within-group studies that examine
      variability across ethnocultural groups identified as belonging to the same
      racial group. Indeed, there was variation in the manifestations of positive
      parenting within and across the ethnic groups included in this study (i.e.,
      African Americans and Caribbean immigrants) that can inform future research and
      practice. (PsycINFO Database Record

PMID- 29172574
TI  - Gender and violence risk assessment in prisons.
AB  - Our study examines the association between Historical, Clinical, Risk Management
      20: Version 2; Psychopathy Checklist-Revised; and Violence Risk Assessment Guide
      scores and violence perpetrated during incarceration by male and female inmates.
      Using a sample of 288 men and 183 women selected from prisons in 2 states, we
      used receiver operating characteristics analyses to assess the potential of these
      3 measures to predict threatened, physical, or sexual prison violence measured in
      2 ways: inmate self-report and formal institutional infractions. We found all 3
      instruments to demonstrate moderate to good levels of predictive accuracy for
      both the male and female inmates, a finding that suggests that actuarial,
      structured professional judgment and personality measures perform in a broadly
      comparable manner in assessing institutional violence for both men and women. Our
      findings did vary on the basis of the way violence was measured: Women self
      reported significantly higher levels of prison violence than was suggested by
      their institutional infractions, and the associative power of the instruments
      diminished substantially, particularly among the men, when institutional
      infractions alone were used in the analyses. These findings suggest that the 3
      risk measures are likely to be gender neutral in their association with prison
      violence, albeit with gender-related differences in the frequency of violent
      behavior and the relevance of particular subscales. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 29172575
TI  - 125th anniversary of the American Psychological Association-Accomplishments and
      challenges: Introduction to the special issue.
AB  - In 2017, the American Psychological Association (APA) celebrates the 125th
      anniversary of its founding. This special issue commemorates this milestone by
      providing long- and short-term views on the history of APA and its role in
      psychology in America. The opening paper presents an overview of initiatives and
      challenges facing the field of psychology and APA in five periods, each roughly
      25 years in length. The remaining eight articles review specific issues and areas
      of activity over varying lengths of time in more recent years. Issues of policy
      involvement, relations with the media, and involvement with the courts are
      described, as well as developments related to social justice, education, science,
      practice, and publications. (PsycINFO Database Record

PMID- 29172576
TI  - 125 years of the American Psychological Association.
AB  - The American Psychological Association (APA) began 125 years ago as a small club
      of a few dozen members in the parlor of its founder, G. Stanley Hall. In the
      decades since, it has faced many difficulties and even a few existential crises.
      Originally a scientific society, it spent the decades between the world wars
      figuring out how to accommodate the growing community of applied psychologists
      while still retaining and enhancing its scientific reputation. After World War
      II, with an expanded mandate, it developed formal training models for clinical
      psychologists and became an important player in legal cases pertaining to civil
      rights and other social justice issues. With practitioners taking an ever-greater
      role in the governance of the organization in the late 1970s, and the financial
      viability of the association in doubt in the 1980s, many psychological scientists
      felt the need to create a separate organization for themselves. The 1990s and
      early 2000s brought more challenges: declining divisional memberships; a legal
      dispute over fees with practitioners; and a serious upheaval over the APA Board
      of Directors' cooperation with governmental defense and intelligence agencies
      during the "war on terror." These clashes appear to have precipitated a decline
      in the association's membership for the first time in its history. The APA has
      faced many storms over its century-and-a-quarter, but has, thus far, always
      ultimately found a way forward for itself, for its members, and for the wider
      discipline of psychology. (PsycINFO Database Record

PMID- 29172577
TI  - Psychology, public policy, and advocacy: Past, present, and future.
AB  - This article offers a historical perspective on the contributions of the field of
      psychology and the American Psychological Association (APA) to the public policy
      arena. It traces APA's involvement from a 1956 Council of Representatives
      resolution on the application of psychology to inform public policy to current
      advocacy initiatives related to psychological science, practice, and education in
      the public interest. Attention is directed to APA's early policy structures
      together with the development of affiliated state, provincial, and territorial
      psychological associations and the first political action committee for
      psychology. The criteria for engagement in advocacy and the goals and functions
      of APA's policy and advocacy initiatives, including the APA Congressional and
      Executive Branch Science Fellowship Program, are also discussed. The evolution of
      psychology's public policy role is illustrated by an increasing level of federal
      advocacy engagement and effectiveness over time, as well as by the emergence of
      psychology leaders in Congress and the Executive Branch. The authors' concluding
      reflections on the future of psychology in the public policy arena derive from
      their many years of experience working on or with Capitol Hill, at APA as elected
      officials or senior staff, and in various roles in academia, think tanks, service
      delivery, and the private sector. (PsycINFO Database Record

PMID- 29172578
TI  - APA's amicus curiae program: Bringing psychological research to judicial
      decisions.
AB  - An important part of the American Psychological Association's (APA) mission is to
      advance psychological science "to promote health, education, and public welfare."
      Organizations with powerful influence on human welfare include state and federal
      appellate courts, especially the U.S. Supreme Court. Initially, APA's amicus
      briefs focused on issues of importance to both individual psychologists and
      public policy. As the program evolved, APA increasingly focused on informing the
      courts about psychological science relevant to important legal issues, including
      criminal, civil, juvenile, education, disability, and human rights law. These
      briefs, and the science that supported them, consistently challenged
      stereotypical beliefs of laypeople with solid, easily understood empirical
      research. APA impartially advocates for the use of psychological science research
      findings by the courts, not on behalf of parties. Volunteer experts, including
      representatives of relevant APA divisions, participate in creating APA briefs. On
      occasion, other scientific organizations may join with APA in its filings. The
      measure of an amicus brief is broader than citations in appellate decisions.
      Although APA's briefs have been cited many times by courts, a broader impact of
      APA briefs is seen by references to psychosocial research provided by APA in
      decisions where its briefs were not specifically cited. APA briefs are being read
      and are affecting major legal decisions. For APA, the relevant question is not
      whether its briefs "prevailed" in a case but whether the court was able to render
      a more informed decision. An important benefit of APA's amicus program has been
      advancing both the reputation of psychological science and APA. (PsycINFO
      Database Record

PMID- 29172579
TI  - Public education and media relations in psychology.
AB  - This article reviews psychology's attempts to influence public attitudes about
      both the science and the profession of psychology. The early history of the
      profession is reviewed, and the efforts of the American Psychological Association
      (APA) to shape the public's perception of psychology are discussed. The rise of
      social media is reviewed, and important social media outlets relevant to
      psychology are identified. The activities of the Society for Media Psychology and
      Technology (APA Division 46) are illustrated, and the presidents of the Division
      are identified. The work of those psychologists who are noted public
      intellectuals or who have received Nobel prizes or National Medal of Science
      awards for their research is briefly reviewed, and the public notoriety of 4
      prominent media celebrities (Joy Browne, Joyce Brothers, Laura Schlessinger, and
      Phil McGraw) is discussed. Several controversies in the field of psychology that
      have influenced the public and their attitudes about psychology are also briefly
      reviewed. (PsycINFO Database Record

PMID- 29172580
TI  - APA efforts in promoting human rights and social justice.
AB  - This article reviews the American Psychological Association's (APA) efforts in
      promoting human rights and social justice. Beginning with a historical review of
      the conceptualizations of human rights and social justice, the social challenges
      that have faced the United States over time are discussed in relation to the
      APA's evolving mission and strategic initiatives enacted through its boards,
      committees, and directorates. From early efforts on the Board for Social and
      Ethical Responsibility in Psychology and the Board of Ethnic Minority Affairs to
      the establishment of the Public Interest Directorate, the APA's efforts to
      address these human rights and social justice challenges through its task force
      reports, guidelines, and policies are described. Specifically, issues related to
      diversity and underrepresentation of minority group members and perspective
      within the APA, as well as women's issues (prochoice, violence against women,
      sexualization of young girls, human trafficking) were central to these efforts.
      These minority groups included racial and ethnic minority groups; immigrants and
      refugees; lesbian, gay, bisexual, transgendered, and queer individuals; and those
      with disabilities. Later attention shifted to broader social justice challenges
      within a public health perspective, such as AIDS, obesity, and violence. Also
      included is a brief discussion of the Hoffman Report. The article ends with a
      discussion of future directions for the APA's efforts related to human rights and
      social justice related to health disparities, violent extremism, social
      inequality, migration, cultural and racial diversity, and an evidence-based
      approach to programming. (PsycINFO Database Record

PMID- 29172581
TI  - Twenty-five years of education in psychology and psychology in education.
AB  - This article is part of a special issue of the American Psychologist celebrating
      the American Psychological Association's (APA's) 125th anniversary. The article
      reviews the last quarter century (1991-2016) of accomplishments by psychology's
      education and training community and APA's Education Directorate. The purpose is
      to highlight key trends and developments over the past quarter century that
      illustrate ways the Directorate sought to advance education in psychology and
      psychology in education, as the Directorate's mission statement says. The focus
      of the Directorate has been on building a cooperative culture across psychology's
      broad education and training community. Specifically APA has (a) promoted quality
      education-from prekindergarten through lifelong learning, (b) encouraged
      accountability through guidelines and standards for education and training, and
      (c) supported the discovery and dissemination of new knowledge to enhance health,
      education, and well-being. After identifying challenges and progress, the article
      discusses the future of the field of psychology and the preparation of its
      workforce of tomorrow. (PsycINFO Database Record

PMID- 29172582
TI  - NIH behavioral and social sciences research support: 1980-2016.
AB  - The history of behavioral and social science research funding at the National
      Institutes of Health (NIH) between 1980 and 2016 is reviewed. Noncommunicable
      diseases are now the primary cause of death worldwide and most are strongly
      linked to behavior. Developed under the prevailing zeitgeist of the biomedical
      model, behavioral and social science has often been underfunded at NIH. In 1990,
      the Senate Appropriations Committee, recognizing that behavior may contribute to
      about half of all premature deaths, recommended that funding for behavioral and
      social sciences research should be about 10% of the NIH budget. NIH and American
      Psychological Association efforts to address this goal are described. Data from
      several sources suggest that this goal has never been realized. Patterns of
      federal funding for research may have a significant influence on scientific
      disciplines. Fields of study that have received more extramural funding are
      associated with greater growth in faculty and higher faculty salaries. A renewed
      effort to increase the federal investment in behavioral and social sciences
      research is necessary. (PsycINFO Database Record

PMID- 29172583
TI  - A quarter century of psychological practice in mental health and health care:
      1990-2016.
AB  - Powerful forces have shaped professional psychology over the past 25 years,
      including significant changes in health policy and health care delivery systems.
      Examples include managed care cost containment, rapid growth of nondoctoral
      mental health providers, federal mental health parity legislation, and passage of
      the Affordable Care Act of 2010, with its emphasis on primary care-behavioral
      health integration and alternatives to fee-for-service reimbursement. This
      article considers these factors for psychology as a mental health profession and
      as a health profession more broadly defined, and describes the American
      Psychological Association's advocacy about the value of psychology in each
      domain. While challenging to psychology's traditional models of care, these
      changes offer significant promise for the future of psychology in health care.
      (PsycINFO Database Record

PMID- 29172584
TI  - From print to digital (1985-2015): APA's evolving role in psychological
      publishing.
AB  - Knowledge dissemination plays an important role in all scientific fields. The
      American Psychological Association's (APA) journal publication program was
      established in 1927. During the 1960s, the Psychological Abstracts publication
      was computerized. In the mid-1980s, a reenergizing of APA Publishing began, with
      the establishment of the APA Books Program, as well as the movement of abstracts
      to CD-ROMs. This article describes the 30-year program of expansion of APA
      Publishing, covering the period from 1985 through 2015. This period saw the
      journals program grow from 15 journals to 89 journals, the abstract program grow
      into an Internet-based delivery system, the creation of the APA's own PsycNET
      delivery platform, the creation of 6 addition databases, and the establishment of
      dictionaries and handbooks of psychology. (PsycINFO Database Record

PMID- 29172585
TI  - An eye-tracking examination of readers' sensitivity to pragmatic scope
      information during the processing of conditional inducements.
AB  - Previous research into conditional inducements has shown that readers are
      sensitive after reading such conditionals to pragmatic scope differences between
      promises and threats; specifically, threats can be referred to as promises, but
      promises cannot be referred to as threats. Crucially, previous work has not
      revealed whether such scope effects emerge while processing the conditional
      itself. In the experiment reported here, participants' eye movements were
      recorded while they read vignettes containing conditional promises and threats.
      We observed a reading time penalty on the conditional itself when participants
      read a conditional promise that was described as a "threat" (e.g., Liam
      threatened Perry "if you tell dad, then I'll take equal responsibility"). There
      was no such penalty when the word "promise" was presented before a conditional
      threat. These results suggest that readers are sensitive during reading of the
      conditional itself to pragmatic scope differences between "threats" and
      "promises." (PsycINFO Database Record

PMID- 29172586
TI  - Alpha span: A measure of working memory.
AB  - In the alpha span test, short lists of words are presented and the participant's
      task is to mentally reorder the words and give them back in correct alphabetical
      order. Alpha span is the longest list of words correctly recalled; the article
      also describes a scoring method in which credit is given for partially correct
      answers. Alpha span provides a quick and easily completed measure of verbal
      numerical working memory (WM), and evidence is presented to show that it is also
      a valid and reliable measure. One purpose of the article is to present data on
      age-related differences in WM in participants 17 to 87 years of age. These data
      show that alpha span is highest in people in their 20s and then declines
      systematically from the 20s to the 80s. A 2nd purpose is to report data on the
      reliability of the alpha span measure and explore its relationships with other
      cognitive measures. The article concludes with some comments on the nature of WM
      as illustrated by alpha span; specifically, we suggest that WM reflects both
      domain-general executive functions and specific abilities in the domain tapped by
      the task in question. (PsycINFO Database Record

PMID- 29172587
TI  - Entrainement de la memoire de travail : Effets sur la performance en
      mathematiques.
AB  - The main components of working memory (WM; Baddeley & Hitch, 1974), central
      executive, phonological loop and visuospatial sketchpad, are related to
      mathematics skills (Friso-van den Bos, Van der Ven, Kroesbergen, & Van Luit,
      2013). Different studies have shown that WM training can increase WM capacity
      (Randall & Tyldesley, 2016). In that context, this research seeks to verify the
      effects of WM training on the components of WM as well as on performance in
      arithmetic and in problem solving among students in the first grades of primary
      school (6 to 8 years of age). The project also seeks to verify whether
      improvements are maintained over a six-month period and whether the training has
      a differential effect in mathematics depending on initial WM capacities. The
      results of this randomized and controlled study indicate that only central
      executive capacities are improved by WM training. Gains in verbal modality tend
      to be maintained over six months while visuo-spatial improvement does not. There
      was no observable effect on mathematic skills. However, WM training has a
      differential effect on problem solving, since children who had low initial WM
      performance did improve their problem solving performance. In conclusion, the
      effects of WM training are specific, generally to the central executive, and
      differentially to problem solving skills among those students with lower WM
      capacities. (PsycINFO Database Record

PMID- 29172588
TI  - Things can change: Sentence processing in consecutive translation.
AB  - Syntactic cues help individuals to assign thematic roles (agent/patient) during
      sentence processing. In the present study, we examined whether the use of
      syntactic cues changed in bilinguals depending on the task they performed.
      Spanish (L1)/English (L2) bilinguals read sentences in Spanish either to produce
      them in the same language or to translate them in English. Three syntactic cues
      were evaluated: animacy (Experiment 1), subject-verb agreement (Experiment 2),
      and word order (Experiment 3). In Experiments 1 and 2, word order was stronger
      than animacy and subject-verb agreement when bilinguals read for translation.
      Moreover, when the same syntactic cue favoured a different agent for each
      language (word order in Experiment 3), the bilinguals performed as native
      speakers of Spanish in the within-language task, whereas they performed as native
      speakers of English in the translation task. Together, this research indicates
      that translation changes the way bilinguals use syntactic cues in sentence
      processing. (PsycINFO Database Record

PMID- 29172589
TI  - Disentangling the link between posttraumatic stress disorder and violent
      behavior: Findings from a nationally representative sample.
AB  - OBJECTIVE: Although research using combat veteran samples has demonstrated an
      association between posttraumatic stress disorder (PTSD) and violence toward
      others, there has been relatively little research examining this relationship
      among individuals with no combat history. METHOD: Data representative of the
      United States population collected from the two wave National Epidemiologic
      Survey on Alcohol and Related Conditions (NESARC) were analyzed to determine the
      risk factors for violent behavior of individuals reporting no history of active
      military combat (N = 33,215). RESULTS: In chi2 analyses, participants meeting
      criteria for lifetime PTSD at Wave 1 reported higher rates of violence between
      Waves 1 and 2 compared with participants without a history of PTSD (7 vs. 3%). An
      increase in anger after trauma and use of alcohol to cope with PTSD symptoms were
      stronger predictors of physically aggressive or violent acts than a lifetime
      diagnosis of PTSD without anger. When controlling for these and other covariates,
      PTSD alone no longer significantly predicted any subtype of physical aggression
      or violence toward others. CONCLUSIONS: Results suggest that although PTSD is
      related to violent behavior, specific sequelae of trauma (specifically, increased
      anger and self-medicating with alcohol) are more critical than diagnosis per se
      in predicting violent behavior in the general population. Clinical implications
      and future research directions are discussed. (PsycINFO Database Record

PMID- 29172590
TI  - The mediating effect of family cohesion in reducing patient symptoms and family
      distress in a culturally informed family therapy for schizophrenia: A parallel
      process latent-growth model.
AB  - OBJECTIVE: Although both patients with schizophrenia and their caregivers report
      elevated levels of depression, anxiety, and stress (DASS), affective symptoms in
      patients and family members seldom constitute a primary treatment focus. The
      present study tested whether a culturally informed family therapy for
      schizophrenia (CIT-S) outperformed standard family psychoeducation (PSY-ED) not
      only in decreasing patient schizophrenia symptoms, but also in decreasing
      individual DASS. Because CIT-S fostered family cohesion throughout treatment, we
      predicted that increases in family cohesion would mediate treatment effects.
      METHOD: Participants included 266 patients and family members nested within 115
      families, randomized to the CIT-S or PSY-ED conditions. We specified a series of
      multilevel latent growth and latent change models to examine direct effects of
      CIT-S on patient schizophrenia symptoms, individual DASS, and family cohesion
      over time. Next, we used parallel-process growth models to test the indirect
      effect of CIT-S on decreasing patient and caregiver psychopathology over time via
      changes in family cohesion. RESULTS: The CIT-S treatment significantly reduced
      patient schizophrenia symptoms from baseline to follow-up (gamma = -1.72, 95%
      confidence interval [CI] [-2.83, -0.60]), as well as individual DASS (gamma = 
      4.39, 95% CI [-6.44, -2.34]) from baseline to termination. In line with treatment
      goals, CIT-S increased family cohesion from baseline to midpoint (gamma = 0.93,
      95% CI [0.06, 1.80]). The CIT-S-related change in cohesion mediated changes in
      DASS (gamma = -0.87, 95% CI [-1.47, -0.27]), but not patient symptoms.
      CONCLUSION: By integrating the family's cultural context into treatment,
      clinicians may foster family dynamics that enhance treatment outcomes and promote
      broad improvements in mental health. (PsycINFO Database Record

PMID- 29172591
TI  - A prospective investigation of the synergistic effect of change in anxiety
      sensitivity and dysphoria on tobacco withdrawal.
AB  - OBJECTIVE: Prevailing theory and research suggests the psychological and
      physiological discomfort associated with tobacco withdrawal may play a formative
      role in the risk of cessation failure. Yet, research elucidating cognitive
      affective vulnerability characteristics that contribute to increased tobacco
      withdrawal severity during periods of planned abstinence is highly limited. In
      the current study, we explored whether smokers with greater reductions of Anxiety
      Sensitivity (AS) and dysphoria during a smoking cessation intervention would
      experience less severe postquit tobacco withdrawal. METHOD: Specifically, the
      interactive effect of change (from preintervention baseline to quit day) in AS
      and dysphoria in relation to postquit withdrawal severity (quit day through 12
      weeks postquit) was examined among treatment-seeking adult smokers enrolled in a
      smoking cessation trial (N = 198; 55.3% female; 86.8% Caucasian; Mage = 38.8, SD
      = 14.0). RESULTS: Results indicated that the interactive effect of change in AS
      and dysphoria was related to linear change in postquit withdrawal symptoms.
      Specifically, larger reductions in AS were associated with a faster decline in
      the severity of withdrawal symptoms across the 12-week postquit period only for
      individuals with lower (but not higher) reductions in dysphoria. Additionally,
      the findings indicated that reducing levels of AS and dysphoria prequit is
      broadly related to the degree of change in postquit withdrawal symptoms.
      CONCLUSION: Collectively, these data suggest there is apt to be clinical merit to
      employing strategies to address AS and/or dysphoria to more effectively manage
      emergent withdrawal symptoms following smoking cessation treatment. (PsycINFO
      Database Record

PMID- 29172593
TI  - Internet-based cognitive behavioral therapy versus psychoeducation control for
      illness anxiety disorder and somatic symptom disorder: A randomized controlled
      trial.
AB  - OBJECTIVE: To examine the efficacy of an Internet-delivered cognitive-behavioral
      therapy (iCBT) program for health anxiety compared to an active psychoeducation
      control group. METHOD: Individuals (N = 86, mean age: 30 years, 87% female) with
      a Diagnostic and Statistical Manual of Mental Disorders (5th ed.) diagnosis of
      illness anxiety disorder or somatic symptom disorder with health anxiety were
      randomized to either a 6-lesson clinician-guided iCBT program for health anxiety
      (n = 45) or an active control group who received anxiety psychoeducation,
      clinical support, and monitoring (control, n = 41) over a 12-week period.
      RESULTS: Both groups experienced significant improvements between baseline and
      posttreatment on self-report measures of health anxiety, depression, general
      anxiety, and functional impairment. Intention-to-treat analyses indicated that
      the iCBT group experienced greater improvements in health anxiety on the Short
      Health Anxiety Inventory (SHAI) compared to controls (between-groups effect size
      = 1.39, 95% confidence interval [0.87, 1.93]), and a greater proportion of the
      iCBT group showed clinically reliable change on the SHAI (84% vs. 34% in the
      control group). Similarly, the iCBT group outperformed the control group on
      secondary measures of depression, generalized anxiety, functional impairment,
      maladaptive cognitions, body hypervigilance, safety behaviors and avoidance, and
      intolerance of uncertainty. Gains were maintained at 3-month follow-up in the
      iCBT group. CONCLUSION: iCBT for health anxiety is more effective than
      psychoeducation, clinical support, and monitoring, and presents an efficacious
      and accessible treatment option for people with health anxiety. (PsycINFO
      Database Record

PMID- 29172592
TI  - Non-suicidal self-injury and suicidal thoughts and behaviors: A study of the
      explanatory roles of the interpersonal theory variables among military service
      members and veterans.
AB  - OBJECTIVE: Research has identified non-suicidal self-injury (NSSI) as a robust
      correlate of suicidal thoughts and behaviors; however, little is known regarding
      why these constructs may be related. Consistent with the interpersonal theory of
      suicide, this study investigated thwarted belongingness (TB), perceived
      burdensomeness (PB), and capability for suicide (CS) as explanatory links in the
      association between NSSI, ideation, and suicide attempt history. METHOD: Military
      service members and veterans (N = 973; agemean = 29.9 years, 78.8% male, 63.8%
      Caucasian/White) completed measures of lifetime NSSI and suicide attempts;
      current suicidal ideation; TB, PB, and CS; and related psychiatric symptoms.
      Bootstrap moderated mediation analyses were employed to examine whether (a) TB
      moderated the mediating effect of PB on NSSI and ideation, (b) PB moderated the
      mediating effect of TB on NSSI and ideation, and (c) CS moderated the mediating
      effect of TB and PB on NSSI and attempts. RESULTS: TB and PB significantly
      accounted for the relationship between lifetime NSSI and current ideation. TB did
      not moderate the mediating effect of PB on NSSI and ideation, and PB did not
      moderate the mediating effect of TB. However, CS significantly moderated the
      mediating effects of TB and PB on NSSI and attempt history. CONCLUSIONS: The
      interpersonal theory of suicide hypotheses were partially supported. Consistent
      with the theory, the interaction of TB and PB only explained NSSI and attempt
      history among service members with high levels of CS. TB and PB only individually
      explained the association between lifetime NSSI and recent suicidal ideation.
      Prospective studies are warranted to replicate these findings across other
      military samples. (PsycINFO Database Record

PMID- 29172594
TI  - Trajectories of in-session change language in brief motivational interventions
      with mandated college students.
AB  - OBJECTIVE: Brief motivational interventions (BMIs) are currently the most
      efficacious individual intervention for mandated college students. However,
      little is known about how BMIs facilitate client language in relation to
      subsequent changes in alcohol use and problems in mandated student samples.
      METHOD: The current study used the Motivational Interviewing Skills Code (MISC
      2.0; Miller, Moyers, Ernst, & Amrhein, 2003) to code BMI sessions (N = 252) from
      2 randomized clinical trials that led to significant reductions in alcohol use
      and alcohol-related problems in mandated student drinkers. A proportion of change
      language was calculated for each decile (1st to 10th) of the BMI sessions.
      RESULTS: Latent class analyses of in-session speech indicated that there were 3
      distinct trajectories of change language over the course of the session: high (n
      = 59), increasing (n = 122), and low (n = 71). Members of the high trajectory
      group showed higher rates of alcohol-related problems prior to the BMI and
      members of the low trajectory group were more likely to be male. Six months
      following the BMI, members of the high and low trajectory groups demonstrated
      significant reductions in alcohol use and problems, and members of the increasing
      trajectory group only reduced alcohol-related problems. CONCLUSIONS: Associations
      among the 3 trajectories of client change language and subsequent reductions in
      alcohol use and problems partially supported the technical hypothesis of MI
      efficacy. Client factors as well as the nature of the discussion of personalized
      feedback may determine the link between in-session client language and subsequent
      behavior change. (PsycINFO Database Record

PMID- 29172595
TI  - Mental health treatment patterns following screening at intake to prison.
AB  - OBJECTIVE: While there is general consensus about the need to increase access to
      mental health treatment, it is debated whether screening is an effective
      solution. We examined treatment use by inmates in a prison system that offers
      universal mental health screening. METHOD: We conducted an observational study of
      7,965 consecutive admissions to Canadian prisons. We described patterns of mental
      health treatment from admission until first release, death, or March, 2015
      (median 14-month follow-up). We explored the association between screening
      results and time of first treatment contact duration of first treatment episode,
      and total number of treatment episodes. RESULTS: Forty-three percent of inmates
      received at least some treatment, although this was often of short duration; 8%
      received treatment for at least half of their incarceration. Screening results
      were predictive of initiation of treatment and recurrent episodes, with stronger
      associations among those who did not report a history prior to incarceration.
      Half of all inmates with a known mental health need prior to incarceration had at
      least 1 interruption in care, and only 46% of inmates with a diagnosable mental
      illness received treatment for more than 10% of their incarceration. CONCLUSION:
      Screening results were associated with treatment use during incarceration.
      However, mental health screening may have diverted resources from the already
      known highest need cases toward newly identified cases who often received brief
      treatment suggestive of lower needs. Further work is needed to determine the most
      cost-effective responses to positive screens, or alternatives to screening that
      increase uptake of services. (PsycINFO Database Record

PMID- 29172596
TI  - Overcoming the research-to-practice gap: A randomized trial with two brief
      homework and organization interventions for students with ADHD as implemented by
      school mental health providers.
AB  - OBJECTIVE: To evaluate the effectiveness of 2 brief school-based interventions
      targeting the homework problems of adolescents with attention
      deficit/hyperactivity disorder (ADHD)-the Homework, Organization, and Planning
      Skills (HOPS) intervention and the Completing Homework by Improving Efficiency
      and Focus (CHIEF) intervention, as implemented by school mental health providers
      during the school day. A secondary goal was to use moderator analyses to identify
      student characteristics that may differentially predict intervention response.
      METHOD: Two-hundred and eighty middle school students with ADHD were randomized
      to the HOPS or CHIEF interventions or to waitlist, and parent and teacher ratings
      were collected pre, post, and at a 6-month follow-up. RESULTS: Both interventions
      were implemented with fidelity by school mental health providers. Participants
      were pulled from elective periods and sessions averaged less than 20 min.
      Participants in HOPS and CHIEF demonstrated significantly greater improvements in
      comparison with waitlist on parent ratings of homework problems and
      organizational skills and effect sizes were large. HOPS participants also
      demonstrated moderate effect size improvements on materials management and
      organized action behaviors according to teachers. HOPS participants made
      significantly greater improvements in parent- and teacher-rated use of organized
      actions in comparison with CHIEF, but not on measures of homework problems.
      Moderation analyses revealed that participants with more severe psychopathology
      and behavioral dysregulation did significantly better with the HOPS intervention
      as compared to the CHIEF intervention. CONCLUSIONS: Brief school-based
      interventions implemented by school providers can be effective. This type of
      service delivery model may facilitate overcoming the oft cited research-to
      practice gap. (PsycINFO Database Record

PMID- 29172597
TI  - "A longitudinal person-centered perspective on youth social support: Relations
      with psychological wellbeing": Correction to Ciarrochi et al. (2017).
AB  - Reports an error in "A longitudinal person-centered perspective on youth social
      support: Relations with psychological wellbeing" by Joseph Ciarrochi, Alexandre
      J. S. Morin, Baljinder K. Sahdra, David Litalien and Philip D. Parker
      (Developmental Psychology, 2017[Jun], Vol 53[6], 1154-1169). In the article, the
      approach utilized (and illustrated in the authors' online supplements) for tests
      of distributional similarity conducted in the context of Latent Transition
      Analyses (LTA) is suboptimal, and has been recently optimized in a webnote
      prepared by Morin and Litalien (2017). This webnote should be consulted by anyone
      thinking to rely on similar methodologies in the LTA context. Importantly,
      distributional similarity was not supported in Ciarrochi et al. (2017) using
      either the initial or optimized method, so that the application of the optimized
      method results in no change in the reported results. As part of this correction,
      the online supplemental materials have been updated to direct readers to the
      webnote. The reference for the Morin and Litalien (2017) webnote is included in
      the erratum. (The following abstract of the original article appeared in record
      2017-17082-001.) Past research suggests that perceived social support from
      parents, teachers, and peers are all positively associated with wellbeing during
      adolescence. However, little longitudinal research has examined the implications
      of distinctive combinations of social support for developing adolescents. To
      address this limitation, we measured multiple dimensions of social support,
      psychological ill-health, and wellbeing in a sample of 2034 Australian
      adolescents (Mage = 13.7; 49.6% male) measured in Grades 8 and 11. Latent
      transition analyses identified a 6-profile solution for both waves of data, and
      revealed substantial inequality in perceived social support. Two "socially rich"
      profiles corresponded to 7% of the sample and had high social support (>1SD above
      sample mean) from at least two sources. (Fully Integrated; Parent and Peer
      Supported). In contrast, 25% of the sample was "socially poor," having support
      that was between -.65 to -.86 SD below the sample mean for all 3 sources
      (Isolated profile). None of the other profiles (Peer Supported; Moderately
      Supported; Weakly Supported) had levels of support below -.37 SD from any source.
      Furthermore, almost all wellbeing problems were concentrated in the Isolated
      Profile, with negative effects more pronounced in Grade 11 than Grade 8. Despite
      feeling low parent and teacher support, adolescents in the Peer Supported profile
      felt strong peer support and average to above-average levels of wellbeing in
      Grades 8 and 11. However, they also had an 81% chance of making a negative
      transition to either the Isolated or Weakly Supported profiles in Grade 11.
      (PsycINFO Database Record

PMID- 29172598
TI  - Biological underpinnings of an internalizing pathway to alcohol, cigarette, and
      marijuana use.
AB  - There is a limited understanding as to how specific genes impact addiction risk.
      Applying a developmental framework and research domain criteria (RDoC) to
      identify etiological pathways from genetic markers to addiction may have utility.
      Prior research has largely focused on externalizing pathways to substance use.
      Although internalizing mechanisms have received less attention, there is strong
      support that addiction is a longer term consequence of using substances to cope
      with internalizing as well as externalizing problems. This study tests whether
      temperament and depression mediate the association between specific genetic
      variants and substance use. The sample consisted of 426 adolescents from the
      Michigan Longitudinal Study (70.9% boys, 84.0% White). Four specific genetic
      variants were examined: SLC6A4 (5HTTLPR), BDNF (rs6265), NPY (rs3037354), and
      CRHBP (rs7728378). Childhood resiliency and behavioral control were examined as
      potential mediators, in addition to early adolescent depression, using a multiple
      mediator path model. Resiliency and depression were supported as mediators in the
      association between genetic risk and later substance use. Important differences
      emerged across substances of abuse. Indirect effects via depression were not
      significant with the inclusion of aggression. Early difficulties with emotional
      coping may represent nonspecific neurobiological underpinnings for an
      internalizing pathway to addiction. (PsycINFO Database Record

PMID- 29172599
TI  - Negative cognitive style interacts with negative life events to predict first
      onset of a major depressive episode in adolescence via hopelessness.
AB  - The hopelessness theory of depression is a prominent account of depression that
      posits that individuals with a negative inferential style are more likely to
      become hopeless when they experience negative life events (NLEs) and that
      hopelessness is a proximal cause of depression. There is strong evidence
      supporting the role of a negative inferential style in the pathogenesis of major
      depression; however, substantially less is known about the proposed role played
      by hopelessness. The cornerstone hypothesis of hopelessness theory, that
      hopelessness is a proximal cause of major depression, is largely untested. A
      small number of studies have generated inconclusive evidence that hopelessness
      mediates the relationship between a negative inferential style, NLEs, and
      depressive symptoms. The current study tested whether hopelessness mediates the
      relationship between a Negative Inferential Style * NLEs interaction and (a) 1st
      onset of a major depressive episode (MDE) and (b) depressive symptoms in a fully
      prospective design. A diverse sample of 249 adolescents, ages 12-13 years, were
      assessed at baseline and at 2 or more follow-ups over approximately 2.5 years.
      Self-report as well as life event and diagnostic interviews assessed inferential
      style, NLEs, hopelessness, depressive symptoms, and depression diagnosis.
      Moderated mediation analyses indicated that hopelessness mediated the
      relationship between a Negative Inferential Style * NLEs interaction and (a) 1st
      onset of an MDE as well as (b) depressive symptoms at higher levels of multiple
      types of NLEs. The current study demonstrates the validity of the hopelessness
      theory of depression and its continued clinical relevance in predicting
      depression in adolescence. (PsycINFO Database Record

PMID- 29172600
TI  - What features of psychopathy might be central? A network analysis of the
      Psychopathy Checklist-Revised (PCL-R) in three large samples.
AB  - Despite a wealth of research, the core features of psychopathy remain hotly
      debated. Using network analysis, an innovative and increasingly popular
      statistical tool, the authors mapped the network structure of psychopathy, as
      operationalized by the Psychopathy Checklist-Revised (PCL-R; Hare, 2003) in two
      large U.S. offender samples (nNIMH = 1559; nWisconsin = 3954), and 1 large Dutch
      forensic psychiatric sample (nTBS = 1937). Centrality indices were highly stable
      within each sample, and indicated that callousness/lack of empathy was the most
      central PCL-R item in the 2 U.S. samples, which aligns with classic clinical
      descriptions and prototypicality studies of psychopathy. The similarities across
      the U.S. samples offer some support regarding generalizability, but there were
      also striking differences between the U.S. samples and the Dutch sample, wherein
      the latter callousnesss/lack of empathy was also fairly central but
      irresponsibility and parasitic lifestyle were even more central. The findings
      raise the important possibility that network-structures do not only reflect the
      structure of the constructs under study, but also the sample from which the data
      derive. The results further raise the possibility of cross-cultural differences
      in the phenotypic structure of psychopathy, PCL-R measurement variance, or both.
      Network analyses may help elucidate the core characteristics of
      psychopathological constructs, including psychopathy, as well as provide a new
      tool for assessing measurement invariance across cultures. (PsycINFO Database
      Record

PMID- 29172601
TI  - Reciprocal variations in sleep and drinking over time among heavy-drinking young
      adults.
AB  - Prior studies have established an association between sleep problems during early
      adolescence and heavy alcohol use/alcohol use disorder (AUD) risk in late
      adolescence. Less research has explored the association between sleep problems
      and heavy alcohol use during young adulthood, the period when AUD onset peaks.
      Moreover, research to date has primarily utilized cross-sectional, between
      subjects' methods to examine this relationship, with limited focus on the
      potential intraindividual variation in these behaviors. Multilevel modeling
      techniques are well-suited to examine the variability in sleep problems and risky
      alcohol use over time and the dynamic bidirectional relations among these
      behaviors. This article reports on 42 heavy-drinking college students at-risk for
      an AUD based on their responses to a validated alcohol screener who completed
      daily diaries of sleep and alcohol use and wore a sleep-wake activity monitor
      (i.e., Philips Respironics Actiwatch 2TM) daily for 7 days yielding a total of
      294 reports. Hierarchical linear models demonstrated that days of heavy drinking
      predicted delayed bed and wake times within individuals and those individuals who
      tended to drink more heavily on average had shorter sleep durations. Conversely,
      days of shorter sleep duration, earlier wake times, and greater perceived sleep
      quality upon waking predicted greater alcohol use within individuals, and those
      who tended to feel more alert upon waking drank more on average. These results
      highlight important within- and between-person variability in the associations
      among objective and subjective sleep-related problems and at-risk drinking among
      young adults. Further, the results have implications for alcohol
      prevention/intervention strategies for young adults at risk for AUDs. (PsycINFO
      Database Record

PMID- 29172603
TI  - Trait emotion regulation strategies and diurnal cortisol profiles in healthy
      adults.
AB  - OBJECTIVE: Experimental studies have shown that 2 emotion regulation strategies
      suppression and reappraisal-are associated with differential profiles of
      physiological activation in response to a stress test. The present study aims to
      add to those findings by investigating whether individual differences in trait
      emotion regulation strategies are associated with diurnal cortisol patterns in a
      naturalistic context. METHOD: A sample of 46 men and women from the Midlife in
      the United States II (MIDUS II) study completed the Emotion Regulation
      Questionnaire (ERQ) and provided 4 salivary cortisol samples per day over 4
      consecutive days. Trait reappraisal and suppression were tested as predictors of
      3 cortisol parameters averaged across days: cortisol awakening response (CAR),
      diurnal cortisol slope (DCS), and area under the curve with respect to ground
      (AUCg). RESULTS: Higher scores on the suppression scale were associated with more
      physiological activation, as indicated by steeper CAR and flatter DCS.
      Suppression was not associated with AUCg, and reappraisal was not predictive of
      any cortisol parameter. CONCLUSIONS: Individual differences in suppression, but
      not reappraisal, were linked to greater cortisol activation in this naturalistic
      study. These preliminary results add to a growing body of findings that link
      suppression to adverse psychological and physiological profiles. (PsycINFO
      Database Record

PMID- 29172602
TI  - Personality and sleep quality: Evidence from four prospective studies.
AB  - OBJECTIVE: The present study examined the longitudinal association between
      personality traits and sleep quality in 4 samples of middle-aged and older
      adults. METHOD: Participants (N > 22,000) were adults aged 30 to 107 years old
      from the Wisconsin Longitudinal Study (WLS), the Midlife in the United States
      Study (MIDUS), the Health and Retirement Study (HRS), and the Midlife in Japan
      Study (MIDJA). Personality and sleep quality were assessed at baseline and again
      4 to 10 years later. RESULTS: Scoring lower on neuroticism and higher on
      extraversion was associated with better sleep quality at baseline and over time,
      with effect sizes larger than those of demographic factors. Low conscientiousness
      was associated with a worsening of sleep quality over time. Openness and
      agreeableness were unrelated to sleep quality. Poor sleep quality at baseline was
      associated with steeper declines in extraversion, agreeableness, and
      conscientiousness and a smaller decrease in neuroticism over time. CONCLUSION:
      Replicable findings across samples support longitudinal associations between
      personality and sleep quality. This study identified specific personality traits
      that are associated with poor and worsening sleep quality, and substantiated
      previous findings that poor sleep quality is associated with detrimental
      personality trajectories. (PsycINFO Database Record

PMID- 29172604
TI  - Daily diary study of hope, stigma, and functioning in lung cancer patients.
AB  - OBJECTIVE: Given its lethality, associated stigma, and symptom burden, a lung
      cancer diagnosis poses a substantial challenge for patients. The goal of this
      study was to examine how daily hope, defined as goal-directed effort and planning
      to meet goals, and daily stigma were related to same- and next-day functioning in
      lung cancer patients receiving cancer treatment. METHODS: Fifty lung cancer
      patients (39 non-small-cell stages IIIa-IV; 11 limited and extensive small cell)
      completed a baseline questionnaire and 21 daily diaries (n = 1,042) assessing
      hope, stigma, physical symptoms, treatment factors, and functioning. Hypotheses
      were tested in same- and next-day models with multilevel modeling. RESULTS:
      Patients who reported more daily hope reported higher social and role functioning
      in same- and next-day models. On days that patients reported more hope than usual
      (compared with their own across-day average), they had higher social, role, and
      physical functioning; this effect did not carry into the next day. Treatment days
      were associated with lower social and role functioning when patients reported
      lower hope and associated with higher functioning when patients reported higher
      hope. Within-person hope was not predicted by disease symptoms. On days that
      patients reported more stigma than usual, they reported lower social and role
      functioning. CONCLUSIONS: Hope is associated with functioning in lung cancer
      patients, regardless of physical symptoms from disease and treatment. Hope and
      stigma may therefore be appropriate intervention targets to support daily social
      and role functioning during lung cancer treatment. (PsycINFO Database Record

PMID- 29172605
TI  - Treatment of depressive symptoms in patients with breast cancer: A randomized
      controlled trial comparing cognitive therapy and bright light therapy.
AB  - OBJECTIVE: This randomized controlled trial (RCT), conducted in patients with
      breast cancer, aimed to compare the effects of cognitive therapy (CT), bright
      light therapy (BLT), and a waiting-list control condition (WLC) on depressive
      symptoms. METHOD: Sixty-two women were randomly assigned to an 8-week CT (n =
      25), BLT (n = 26), or WLC (n = 11). Participants completed the depression
      subscale of the Hospital Anxiety and Depression Scale (HADS-D), the Beck
      Depression Inventory-II (BDI-II), and the Hamilton Depression Rating Scale (HDRS)
      at pre- and posttreatment (and postwaiting for WLC), as well as 3 and 6 months
      later. RESULTS: At posttreatment, CT patients had a significantly greater
      reduction of depressive symptoms than WLC on the HADS-D and the BDI-II. BLT
      patients had a greater reduction of depressive symptoms than WLC on the HADS-D
      only. After WLC participants were reassigned to CT or BLT, a superiority of CT
      over BLT was found on the BDI-II at posttreatment. Patients of both active
      conditions showed a good sustainment of treatment gains at follow-ups.
      CONCLUSIONS: Although replication with larger samples is needed, these results
      confirm the efficacy of CT for depression in the context of breast cancer and
      suggest that BLT could be of some utility when CT is not available or desired.
      (PsycINFO Database Record

PMID- 29172606
TI  - Ecological momentary assessment of self-attitudes in response to dietary lapses.
AB  - OBJECTIVE: To examine whether self-attitudes and self-efficacy after dietary
      lapses relate to lapse frequency or predict risk for lapsing again on the same
      day. METHOD: Adults with overweight/obesity (n = 91) completed ecological
      momentary assessment for 14 days at the start of a lifestyle modification
      program. At each survey, participants reported whether they had experienced a
      dietary lapse, and, if so, reported their self-attitudes (i.e., self-criticism,
      self-forgiveness, self-regard) and self-efficacy. The relationships between
      participants' typical (i.e., average level for each participant across lapses)
      self-attitudes/self-efficacy after lapsing and lapse frequency were examined
      using correlations. Generalized estimating equations examined whether
      participants' typical (average across lapses; between-person effect) self
      attitudes/self-efficacy or momentary (i.e., level of each variable at a
      particular lapse relative to one's typical level; within-person effect) self
      attitudes/self-efficacy predicted same-day lapse occurrence. RESULTS: Lower
      typical self-efficacy and more negative typical self-regard related to greater
      lapse frequency. Additionally, lower momentary self-criticism predicted greater
      likelihood of same-day lapse occurrence. There also was a quadratic relationship
      between typical self-regard and risk of same-day lapse occurrence, such that
      individuals with either more negative or more positive typical self-regard were
      more likely to lapse on the same day. CONCLUSION: Findings provide preliminary
      support for the relevance of self-attitudes and self-efficacy to lapses during
      early lifestyle modification. While greater typical self-efficacy and more
      positive typical self-regard are associated with fewer lapses, lower momentary
      self-criticism and very positive or negative typical self-regard may confer risk
      for same-day lapses. (PsycINFO Database Record

PMID- 29172608
TI  - Estimating and testing for differential treatment effects on outcomes when the
      outcome variances differ.
AB  - Researchers working in the context of randomized trials routinely estimate and
      test for treatment effects on the study outcomes. This article discusses the
      merits of assessing differential treatment effects across outcomes and proposes a
      multivariate approach using standardized outcomes for this purpose. This
      multivariate approach extends prior approaches to an arbitrary number of
      treatment groups and outcomes and does not require that the within-group
      covariance matrix have particular properties (e.g., sphericity). Theoretical
      analyses articulate the inferential basis for earlier recommendations for data
      standardization prior to analysis and demonstrate that inferential procedures
      (e.g., null hypothesis significance tests and confidence intervals) can exhibit
      poor operating characteristics when unstandardized outcome data are used for
      analysis and differential standardized treatment effects are the conceptual,
      intended target of inference. This article explores these and other issues (e.g.,
      statistical power to detect and confidence intervals for differential
      standardized treatment effects) and demonstrates the proposed approach using data
      from a published experiment. The theoretical utility of differential treatment
      effect evidence is considered from a construct validity perspective for
      randomized trials. The proposed approach provides inferential procedures to
      evaluate theoretically motivated predictions for differential treatment effects
      on the outcomes; failure to support such predictions either calls the construct
      validity of the randomized trial into question or the underlying theory. The
      proposed approach also enables the detection of differences in treatment effects
      on the outcomes that are not theoretically expected; such results, especially if
      replicated, would motivate the need for theoretical refinements. (PsycINFO
      Database Record

PMID- 29172607
TI  - Social isolation, health literacy, and mortality risk: Findings from the English
      Longitudinal Study of Ageing.
AB  - OBJECTIVE: To investigate the relationships between social isolation, health
      literacy, and all-cause mortality, and the modifying effect of social isolation
      on the latter relationship. METHODS: Data were from 7731 adults aged >=50 years
      participating in Wave 2 (2004/2005) of the English Longitudinal Study of Ageing.
      Social isolation was defined according to marital/cohabiting status and contact
      with children, relatives, and friends, and participation in social organizations.
      Scores were split at the median to indicate social isolation (yes vs. no). Health
      literacy was assessed as comprehension of a medicine label and classified as
      "high" (>=75% correct) or "low" (<75% correct). The outcome was all-cause
      mortality up to February 2013. Cox proportional hazards models were adjusted for
      sociodemographic factors, health status, health behaviors, and cognitive
      function. RESULTS: Mortality rates were 30.3% versus 14.3% in the low versus high
      health literacy groups, and 23.5% versus 13.7% in the socially isolated versus
      nonisolated groups. Low health literacy (adj. HR = 1.22, 95% CI 1.02-1.45 vs.
      high) and social isolation (adj. HR = 1.28, 95% CI 1.10-1.50) were independently
      associated with increased mortality risk. The multiplicative interaction term for
      health literacy and social isolation was not statistically significant (p = .81).
      CONCLUSIONS: Low health literacy and high social isolation are risk factors for
      mortality. Social isolation does not modify the relationship between health
      literacy and mortality. Clinicians should be aware of the health risks faced by
      socially isolated adults and those with low health literacy. (PsycINFO Database
      Record

PMID- 29172609
TI  - Linear mixed-effects models and the analysis of nonindependent data: A unified
      framework to analyze categorical and continuous independent variables that vary
      within-subjects and/or within-items.
AB  - In this article we address a number of important issues that arise in the
      analysis of nonindependent data. Such data are common in studies in which
      predictors vary within "units" (e.g., within-subjects, within-classrooms). Most
      researchers analyze categorical within-unit predictors with repeated-measures
      ANOVAs, but continuous within-unit predictors with linear mixed-effects models
      (LMEMs). We show that both types of predictor variables can be analyzed within
      the LMEM framework. We discuss designs with multiple sources of nonindependence,
      for example, studies in which the same subjects rate the same set of items or in
      which students nested in classrooms provide multiple answers. We provide clear
      guidelines about the types of random effects that should be included in the
      analysis of such designs. We also present a number of corrective steps that
      researchers can take when convergence fails in LMEM models with too many
      parameters. We end with a brief discussion on the trade-off between power and
      generalizability in designs with "within-unit" predictors. (PsycINFO Database
      Record

PMID- 29172610
TI  - Multilevel autoregressive mediation models: Specification, estimation, and
      applications.
AB  - In the current study, extending from the cross-lagged panel models (CLPMs) in
      Cole and Maxwell (2003), we proposed the multilevel autoregressive mediation
      models (MAMMs) by allowing the coefficients to differ across individuals. In
      addition, Level-2 covariates can be included to explain the interindividual
      differences of mediation effects. Given the complexity of the proposed models,
      Bayesian estimation was used. Both a CLPM and an unconditional MAMM were fitted
      to daily diary data. The 2 models yielded different statistical conclusions
      regarding the average mediation effect. A simulation study was conducted to
      examine the estimation accuracy of Bayesian estimation for MAMMs and consequences
      of model mis-specifications. Factors considered included the sample size (N),
      number of time points (T), fixed indirect and direct effect sizes, and Level-2
      variances and covariances. Results indicated that the fixed effect estimates for
      the indirect effect components (a and b) and the fixed effects of Level-2
      covariates were accurate when N >= 50 and T >= 5. For estimating Level-2
      variances and covariances, they were accurate provided a sufficiently large N and
      T (e.g., N >= 500 and T >= 50). Estimates of the average mediation effect were
      generally accurate when N >= 100 and T >= 10, or N >= 50 and T >= 20.
      Furthermore, we found that when Level-2 variances were zero, MAMMs yielded valid
      inferences about the fixed effects, whereas when random effects existed, CLPMs
      had low coverage rates for fixed effects. DIC can be used for model selection.
      Limitations and future directions were discussed. (PsycINFO Database Record

PMID- 29172611
TI  - Permutation randomization methods for testing measurement equivalence and
      detecting differential item functioning in multiple-group confirmatory factor
      analysis.
AB  - In multigroup factor analysis, different levels of measurement invariance are
      accepted as tenable when researchers observe a nonsignificant (Delta)chi2 test
      after imposing certain equality constraints across groups. Large samples yield
      high power to detect negligible misspecifications, so many researchers prefer
      alternative fit indices (AFIs). Fixed cutoffs have been proposed for evaluating
      the effect of invariance constraints on change in AFIs (e.g., Chen, 2007; Cheung
      & Rensvold, 2002; Meade, Johnson, & Braddy, 2008). We demonstrate that all of
      these cutoffs have inconsistent Type I error rates. As a solution, we propose
      replacing chi2 and fixed AFI cutoffs with permutation tests. Randomly permuting
      group assignment results in average between-groups differences of zero, so
      iterative permutation yields an empirical distribution of any fit measure under
      the null hypothesis of invariance across groups. Our simulations show that the
      permutation test of configural invariance controls Type I error rates better than
      chi2 or AFIs when the model contains parsimony error (i.e., negligible
      misspecification) but the factor structure is equivalent across groups (i.e., the
      null hypothesis is true). For testing metric and scalar invariance, Deltachi2 and
      permutation yield similar power and nominal Type I error rates, whereas DeltaAFIs
      yield inflated errors in smaller samples. Permuting the maximum modification
      index among equality constraints control familywise Type I error rates when
      testing multiple indicators for lack of invariance, but provide similar power as
      using a Bonferroni adjustment. An applied example and syntax for software are
      provided. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29172612
TI  - More stable estimation of the STARTS model: A Bayesian approach using Markov
      chain Monte Carlo techniques.
AB  - The STARTS (Stable Trait, AutoRegressive Trait, and State) model decomposes
      individual differences in psychological measurement across time into 3 sources of
      variation: a time-invariant stable component, a time-varying autoregressive
      component, and an occasion-specific state component. Previous simulation research
      and applications of the STARTS model have shown that serious estimation problems
      such as nonconvergence or inadmissible estimates (e.g., negative variances)
      frequently occur for STARTS model parameters. This article introduces a general
      approach to estimating the parameters of the STARTS model by employing Bayesian
      methods that use Markov Chain Monte Carlo (MCMC) techniques. With the
      specification of appropriate prior distributions, the Bayesian approach offers
      the advantage that the model estimates will be within the admissible range, and
      it should be possible to avoid estimation problems. Furthermore, we show how
      Bayesian methods can be used to stabilize STARTS model estimates by specifying
      weakly informative prior distributions for the model parameters. In a simulation
      study, the statistical properties (bias, root mean square error, coverage rate)
      of the parameter estimates obtained from the Bayesian approach are compared with
      those of the maximum-likelihood approach. A data example is presented to
      illustrate how the Bayesian approach can be used to estimate the STARTS model.
      Finally, further extensions of the STARTS model are discussed, and suggestions
      for applied research are made. (PsycINFO Database Record

PMID- 29172613
TI  - Prior sensitivity analysis in default Bayesian structural equation modeling.
AB  - Bayesian structural equation modeling (BSEM) has recently gained popularity
      because it enables researchers to fit complex models and solve some of the issues
      often encountered in classical maximum likelihood estimation, such as
      nonconvergence and inadmissible solutions. An important component of any Bayesian
      analysis is the prior distribution of the unknown model parameters. Often,
      researchers rely on default priors, which are constructed in an automatic fashion
      without requiring substantive prior information. However, the prior can have a
      serious influence on the estimation of the model parameters, which affects the
      mean squared error, bias, coverage rates, and quantiles of the estimates. In this
      article, we investigate the performance of three different default priors:
      noninformative improper priors, vague proper priors, and empirical Bayes priors
      with the latter being novel in the BSEM literature. Based on a simulation study,
      we find that these three default BSEM methods may perform very differently,
      especially with small samples. A careful prior sensitivity analysis is therefore
      needed when performing a default BSEM analysis. For this purpose, we provide a
      practical step-by-step guide for practitioners to conducting a prior sensitivity
      analysis in default BSEM. Our recommendations are illustrated using a well-known
      case study from the structural equation modeling literature, and all code for
      conducting the prior sensitivity analysis is available in the online supplemental
      materials. (PsycINFO Database Record

PMID- 29172614
TI  - A novel measure of effect size for mediation analysis.
AB  - Mediation analysis has become one of the most popular statistical methods in the
      social sciences. However, many currently available effect size measures for
      mediation have limitations that restrict their use to specific mediation models.
      In this article, we develop a measure of effect size that addresses these
      limitations. We show how modification of a currently existing effect size measure
      results in a novel effect size measure with many desirable properties. We also
      derive an expression for the bias of the sample estimator for the proposed effect
      size measure and propose an adjusted version of the estimator. We present a Monte
      Carlo simulation study conducted to examine the finite sampling properties of the
      adjusted and unadjusted estimators, which shows that the adjusted estimator is
      effective at recovering the true value it estimates. Finally, we demonstrate the
      use of the effect size measure with an empirical example. We provide freely
      available software so that researchers can immediately implement the methods we
      discuss. Our developments here extend the existing literature on effect sizes and
      mediation by developing a potentially useful method of communicating the
      magnitude of mediation. (PsycINFO Database Record

PMID- 29172615
TI  - Variable system: An alternative approach for the analysis of mediated moderation.
AB  - Mediated moderation (meMO) occurs when the moderation effect of the moderator (W)
      on the relationship between the independent variable (X) and the dependent
      variable (Y) is transmitted through a mediator (M). To examine this process
      empirically, 2 different model specifications (Type I meMO and Type II meMO) have
      been proposed in the literature. However, both specifications are found to be
      problematic, either conceptually or statistically. For example, it can be shown
      that each type of meMO model is statistically equivalent to a particular form of
      moderated mediation (moME), another process that examines the condition when the
      indirect effect from X to Y through M varies as a function of W. Consequently, it
      is difficult for one to differentiate these 2 processes mathematically. This
      study therefore has 2 objectives. First, we attempt to differentiate moME and
      meMO by proposing an alternative specification for meMO. Conceptually, this
      alternative specification is intuitively meaningful and interpretable, and,
      statistically, it offers meMO a unique representation that is no longer identical
      to its moME counterpart. Second, using structural equation modeling, we propose
      an integrated approach for the analysis of meMO as well as for other general
      types of conditional path models. VS, a computer software program that implements
      the proposed approach, has been developed to facilitate the analysis of
      conditional path models for applied researchers. Real examples are considered to
      illustrate how the proposed approach works in practice and to compare its
      performance against the traditional methods. (PsycINFO Database Record

PMID- 29172616
TI  - Culturally divergent consequences of receiving thanks in close relationships.
AB  - We investigated consequences of receiving thanks in close relationships across
      cultures. Chinese reported more negative feelings than Euro-Canadians after a
      close other said thanks to them. Likewise, Chinese participants predicted, more
      than Euro-Canadians did, that a close other would experience negative feelings
      after receiving thanks from them. No cultural difference was found when receiving
      thanks from an acquaintance. On the other hand, when not receiving thanks from
      close others after helping them, Euro-Canadians experienced more negative
      feelings than did Chinese. We showed that beliefs about saying thanks in close
      relationships accounted for cultural differences in emotions. Implications for
      intercultural communication, relationship maintenance, and directions for future
      research are discussed. (PsycINFO Database Record

PMID- 29172617
TI  - Preference for illusory contours: Beyond object symmetry, familiarity, and
      nameability.
AB  - It has previously been reported that individuals prefer figures from which they
      can extract shapes via illusory contours (Kanisza figures) over figures in which
      this is not possible. However, based on the past research in this area, it is not
      possible to distinguish the influence of illusory contour perception from other
      factors such as the symmetry, familiarity, prototypicality, and nameability of
      the perceived shape. Here, we investigate the influence of illusory contours in
      the absence of these confounding variables by measuring participants'
      aesthetic/liking ratings for symmetric Kanisza figures and for unfamiliar and
      asymmetric Kanisza figures. Results show that illusory contours do indeed
      influence preference above and beyond any effects of these other factors.
      (PsycINFO Database Record

PMID- 29172618
TI  - Visuospatial asymmetries and emotional valence influence mental time travel.
AB  - Spatial information is tightly intertwined with temporal and valence-based
      information. Namely, "past" is represented on the left, and "future" on the
      right, along a horizontal mental timeline. Similarly, right is associated with
      positive, whereas left is negative. We developed a novel task to examine the
      effects of emotional valence and temporal distance on mental representations of
      time. We compared positivity biases, where positive events are positioned closer
      to now, and right hemisphere emotion biases, where negative events are positioned
      to the left. When the entire life span was used, a positivity bias emerged;
      positive events were closer to now. When timeline length was reduced, positivity
      and right hemisphere emotion biases were consistent for past events. In contrast,
      positive and negative events were equidistant from now in the future condition,
      suggesting positivity and right hemisphere emotion biases opposed one another,
      leading events to be positioned at a similar distance. We then reversed the
      timeline by moving past to the right and future to the left. Positivity biases in
      the past condition were eliminated, and negative events were placed slightly
      closer to now in the future condition. We conclude that an underlying left-to
      right mental representation of time is necessary for positivity biases to emerge
      for past events; however, our mental representations of future events are
      inconsistent with positivity biases. These findings point to an important
      difference in the way in which we represent the past and the future on our mental
      timeline. (PsycINFO Database Record

PMID- 29172619
TI  - Differential effects of state and trait mindfulness on the late positive
      potential.
AB  - Mindfulness is an effective emotion regulation strategy, and its principles have
      formed the basis for several psychotherapies. Of interest is how a mindful
      perspective changes not only the subjective experience of emotion, but also
      neural activity involved in emotional processing. In a previous event-related
      potential (ERP) study, trait mindfulness was linked with reduced neural activity
      in response to affective stimuli, as measured by the late positive potential
      (LPP). Building on this result, we investigated how both state (i.e., task
      induced) and trait mindfulness would jointly affect the LPP in a large adult
      sample (N = 118). First, participants passively viewed affective images while ERP
      data were recorded. Participants were then instructed to adopt a mindful
      perspective and viewed a second, equivalent set of images. We hypothesized that
      the LPP would be reduced from the passive viewing to the mindful viewing
      condition. Contrary to our hypothesis, task-induced mindfulness increased LPP
      amplitude relative to passive viewing across all image types, suggesting that
      state mindfulness increases motivated attention to stimuli, regardless of
      affective valence and arousal. Trait mindfulness did not correlate with LPP
      amplitude in either the passive or mindful viewing conditions. As an unexpected
      finding, gender moderated the association between trait mindfulness and LPP
      amplitude to emotional images during mindful viewing. We propose that state and
      trait mindfulness impact emotional processing through different neural mechanisms
      and discuss implications for mindfulness as an emotion regulation strategy.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29172620
TI  - Emotion-color associations in the context of the face.
AB  - Facial expressions of emotion contain important information that is perceived and
      used by observers to understand others' emotional state. While there has been
      considerable research into perceptions of facial musculature and emotion, less
      work has been conducted to understand perceptions of facial coloration and
      emotion. The current research examined emotion-color associations in the context
      of the face. Across 4 experiments, participants were asked to manipulate the
      color of face, or shape, stimuli along 2 color axes (i.e., red-green, yellow
      blue) for 6 target emotions (i.e., anger, disgust, fear, happiness, sadness,
      surprise). The results yielded a pattern that is consistent with physiological
      and psychological models of emotion. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 29172621
TI  - Effects of oxytocin administration on receiving help.
AB  - Receiving help can be a "mixed blessing." Despite the many psychosocial benefits
      it can carry, it sometimes has negative psychological consequences, such as loss
      in self-esteem or enhanced guilt. It is, therefore, important to understand the
      factors that modify responses to receiving help from others. We explored the role
      of the hormone oxytocin (OT) on affective and social responses to receiving help,
      given the putative role of OT in social bonding and attunement. To this end, we
      manipulated whether help was received from a same-sex interaction partner
      (confederate) versus a control condition, crossed with a double-blind
      administration of intranasal OT (vs. placebo), and examined subjective and
      observer-rated participant responses to help. We observed significant
      interactions between OT and the help manipulation. In the placebo condition,
      receiving help from the interaction partner compared with the control condition
      had negative consequences, such that participants reported greater negative
      affect and came to view themselves and their interaction partners more negatively
      after interacting together on several tasks. What is important, however, is that
      OT administration buffered against these negative subjective responses to
      receiving help. Further, outside observers rated participants who received OT
      administration as expressing greater happiness and gratitude in response to help,
      relative to those who received placebo. In sum, in the context of receiving help
      from a stranger, oxytocin administration fostered more positive affective and
      social responses. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29172622
TI  - A multi-method investigation of the association between emotional clarity and
      empathy.
AB  - Higher emotional clarity, the extent to which people unambiguously identify,
      label, and describe their own emotions, is related to a host of positive
      intrapersonal factors but its relation to interpersonal factors is unexplored. We
      hypothesized that emotional clarity would be related to cognitive empathy (i.e.,
      perceiving others' emotions) and to accurately understanding others' negative
      affect (NA), but not positive affect (PA), in the context of a stressful
      situation. After completing self-reports of trait emotional clarity and cognitive
      and affective empathy (i.e., one's emotional reaction to others), participants (N
      = 94 undergraduate students; i.e., perceivers) viewed a series of video clips of
      adults (i.e., targets) completing a stressful laboratory task in a previous
      research study. Before and after the stress task, targets reported their state NA
      and PA. While viewing the recordings, perceivers rated how they thought the
      targets were feeling at the corresponding time points. Correspondence between
      perceivers' and targets' affect ratings were used as indices of the outcome
      variable, performance-based cognitive empathy. As expected, self-reported
      emotional clarity was related to the self-reported cognitive, but not affective,
      empathy. Moreover, perceivers' emotional clarity was related to higher cognitive
      empathy for NA not PA after the stressful task. Our findings provide preliminary
      support for the importance of emotional clarity in the ability to accurately
      understand others' affective experiences, which has important interpersonal
      implications. (PsycINFO Database Record

PMID- 29172623
TI  - The structure of emotional experience and its relation to trait emotional
      awareness: A theoretical review.
AB  - Emotional experience (EE) and trait emotional awareness (tEA) have recently
      become topics of considerable experimental/theoretical interest within the
      cognitive and neural sciences. However, to date there has been limited empirical
      focus on how individual differences in the factors contributing to EE (a state
      based construct) might account for differences in tEA. To promote clear, well
      guided empirical research in this area, in this article we first offer a concise
      review of the primary factors contributing to EE. We then provide a theoretical
      investigation into how individual differences in these factors (i.e., differences
      in affective response generation, affective response representation, and
      conscious access) could mechanistically account for differences in tEA; we also
      discuss plausible origins of these individual differences in light of current
      empirical findings. Finally, we outline possible experiments that would support
      (or fail to support) the role of each factor in explaining differences in tEA-and
      how this added knowledge could shed light on the known link between low tEA and
      multiple emotion-related mental and systemic medical disorders. (PsycINFO
      Database Record

PMID- 29172624
TI  - Parenting behaviors and the well-being of children with a chronic physical
      condition.
AB  - INTRODUCTION: Numerous studies have identified the importance of parenting
      behaviors to the well-being of children with chronic physical conditions.
      Synthesizing the findings of these studies has potential to identify which
      parenting behaviors are associated with specific aspects of child well-being.
      METHOD: We retrieved research reports addressing the relationship between
      parenting behaviors and well-being in children with chronic physical conditions,
      and categorized parenting behaviors based on Skinner, Johnson, and Snyder's
      (2005) core dimensions of parenting (warmth, rejection, structure, chaos,
      autonomy support, and coercion) Through meta-analysis, we examined relationships
      between parenting dimension and child well-being variables. RESULTS: Fifty-four
      reports from 47 unique studies met inclusion criteria. Parent warmth was
      associated with less child depression, better quality of life, better physical
      functioning, and fewer externalizing behavior problems. Parent rejection was
      associated with more child depression, internalizing/externalizing behavior
      problems, and poorer physical functioning. Parent structure was associated with
      better child physical functioning. Parent chaos was associated with poorer child
      physical functioning. Parent autonomy support was associated with better quality
      of life and fewer externalizing behavior problems. Parent coercion was associated
      with more child depression, poorer quality of life, poorer physical function, and
      more internalizing behavior problems. CONCLUSION: The results identify multiple,
      potentially modifiable parenting dimensions associated with well-being in
      children with a chronic condition, which could be targeted in developing family
      focused interventions. They also provide evidence that research using Skinner's
      core dimensions could lead to conceptualization and study of parenting behaviors
      in ways that would enable comparison of parenting in a variety of health and
      sociocultural contexts. (PsycINFO Database Record

PMID- 29172625
TI  - Evaluative coping, emotional distress, and adherence in couples with Type 2
      diabetes.
AB  - INTRODUCTION: Spousal support is one of the strongest and most consistent
      predictors of Type 2 diabetes treatment adherence. However, the effects of both
      spouses' evaluations of dyadic coping on emotional distress and patients'
      physical health remain largely unknown. METHOD: Dyadic data from 117 married
      couples in which one member is diagnosed with Type 2 diabetes were evaluated in
      two separate models to explore the associations between (a) patients' and
      spouses' depression symptoms and patients' adherence to dietary and exercise
      regimens, and (b) patients' and spouses' acute stress levels and patients'
      adherence to dietary and exercise regimens. Finally, evaluative dyadic coping was
      included as a possible moderator between these associations. RESULTS: Results
      from an actor-partner interdependence model revealed significant actor effects of
      patients' depression symptoms on patients' adherence to dietary and exercise
      regimens. Spouses' evaluation of dyadic coping attenuated the direct paths
      between spouses' depression symptoms and patients' adherence to dietary regimens.
      No direct pathways were found from patients' or spouses' acute stress to
      patients' adherence to dietary and exercise regimens. However, spouses'
      evaluation of dyadic coping attenuated the direct paths between spouses' acute
      stress and patients' adherence to dietary regimens. DISCUSSION: Tapping into
      spouses' evaluations of dyadic coping has significant implications for patients'
      diabetes health outcomes (e.g., adherence to dietary and exercise treatment
      regimens). Findings from this study highlight the need for systemic interventions
      targeting both partners. (PsycINFO Database Record

PMID- 29172626
TI  - Attachment, household chaos, and children's health.
AB  - INTRODUCTION: Despite growing interest in the links between sociocontextual
      factors and children's behavioral functioning, few studies have investigated how
      such factors, in combination, relate to health outcomes or vary across mental and
      physical well-being. We evaluated the direct and interactive associations of
      parental attachment and household chaos with preschool-age children's mental and
      physical health. METHOD: Ninety-four parents completed questionnaires about their
      attachment styles, disorganization and confusion in the home, and their
      children's health functioning. RESULTS: Attachment avoidance and anxiety in
      parents predicted poorer mental health in children, particularly in highly
      chaotic homes. Moreover, parental attachment anxiety, but not avoidance,
      predicted poorer reported physical health in children and, in conjunction with
      chaotic homes, more hospitalizations. DISCUSSION: The results help illuminate how
      multiple domains in children's immediate environment jointly influence their
      physical and mental health and how these influences may vary across domains of
      functioning. Findings have implications for targeting interventions to have
      impact across facets of children's health. (PsycINFO Database Record

PMID- 29172627
TI  - Pediatric primary care psychologists' reported level of integration, billing
      practices, and reimbursement frequency.
AB  - INTRODUCTION: Integration of psychological services into pediatric primary care
      is increasingly common, but models of integration vary with regard to their level
      of coordination, colocation, and integration. High-integration models may provide
      some distinct advantages, such as preventative care and brief consultation for
      subclinical behavior concerns; however, psychologists face barriers to seeking
      reimbursement for these services. Alternatives to traditional psychotherapy and
      psychological testing codes, specifically Health & Behavior (H&B) codes, have
      been proposed as 1 method for supporting integrated care. The aim of this study
      was to investigate the relationships between psychologists' reported billing
      practices, reimbursement rates, and model of integration in pediatric primary
      care. METHOD: As part of a larger survey study, 55 psychologists working in
      pediatric primary care reported on characteristics of their practice's model of
      integration, billing practices, and frequency of reimbursement for consultative
      services. RESULTS: Compared with those who categorized their integrated care
      model as colocated, psychologists who endorsed working in integrated models
      reported a significantly higher usage of H&B codes and more frequent
      reimbursement for consultations. Overall, use of H&B codes was associated with
      higher reported levels of coordination and integration. DISCUSSION: Survey
      results showed a clear pattern of higher integration being associated with
      greater utilization of H&B codes and better reimbursement for consultation
      activities. These results underscore the importance of establishing and
      maintaining billing and reimbursement systems that adequately support integrated
      care. (PsycINFO Database Record

PMID- 29172628
TI  - Adolescent and parent perspectives on medical decision-making for chronic
      illness.
AB  - INTRODUCTION: The objective of the study was to assess correlates of adolescent
      and parent perceptions of their involvement in medical decision-making (MDM).
      METHOD: Study participants included 28 pairs of pediatric patients with chronic
      rheumatologic illnesses and their parents presenting to an outpatient
      rheumatology clinic. Participants completed measures assessing perceptions of MDM
      involvement, health consciousness, and decisional conflict. RESULTS: Adolescent
      health consciousness correlated positively with parent health consciousness and
      adolescent-valuing involvement. There was a significant positive correlation
      between adolescents-valuing involvement in medical decisions and perception of
      actual involvement. Adolescents who perceived themselves as more involved in
      their care reported less decisional conflict. Parents who wanted to participate
      in MDM reported greater actual involvement. DISCUSSION: Adolescents who value
      participation in MDM reported higher levels of actual participation, suggesting
      their preferences may be considered by providers. Greater engagement in MDM was
      related to lower decisional conflict for adolescents, suggesting that including
      adolescents in the MDM process does not necessarily result in confusion or
      distress. (PsycINFO Database Record

PMID- 29172630
TI  - Lexical tone is perceived relative to locally surrounding context, vowel quality
      to preceding context.
AB  - Important speech cues such as lexical tone and vowel quality are perceptually
      contrasted to the distribution of those same cues in surrounding contexts.
      However, it is unclear whether preceding and following contexts have similar
      influences, and to what extent those influences are modulated by the auditory
      history of previous trials. To investigate this, Cantonese participants labeled
      sounds from (a) a tone continuum (mid- to high-level), presented with a context
      that had raised or lowered fundamental frequency (F0) values and (b) a vowel
      quality continuum (/u/ to /o/), where the context had raised or lowered first
      formant (F1) values. Contexts with high or low F0/F1 were presented in separate
      blocks or intermixed in 1 block. Contexts were presented following (Experiment 1)
      or preceding the target continuum (Experiment 2). Contrastive effects were found
      for both tone and vowel quality (e.g., decreased F0 values in contexts lead to
      more high tone target judgments and vice versa). Importantly, however, lexical
      tone was only influenced by F0 in immediately preceding and following contexts.
      Vowel quality was only influenced by the F1 in preceding contexts, but this
      extended to contexts from preceding trials. Contextual influences on tone and
      vowel quality are qualitatively different, which has important implications for
      understanding the mechanism of context effects in speech perception. (PsycINFO
      Database Record

PMID- 29172629
TI  - Physician perceptions of children's coping with asthma are associated with
      children's psychosocial and disease functioning.
AB  - INTRODUCTION: Low-income, ethnic minority children disproportionately face poor
      asthma control, and poorly controlled asthma is related to psychosocial
      difficulties. This study assessed physician reports of coping in child patients
      and examined associations between physician reports of child coping and parent
      and child reports of children's coping, psychosocial, and asthma outcomes (asthma
      related stress, emotional and behavioral problems, asthma control, and school
      missed due to asthma). METHOD: Physicians reported on coping in their patients (N
      = 67) ages 5-17 with asthma. Parents reported on child coping, asthma-related
      stress, emotional and behavioral problems, asthma control, and school missed due
      to asthma. Children ages 9-17 provided self-reports. RESULTS: Physicians' reports
      of primary control coping (e.g., problem solving) and secondary control coping
      (e.g., cognitive restructuring) were not associated with parent ratings of
      corresponding coping strategies, but physician reports of disengagement coping
      (e.g., avoidance) were correlated with parent reports of disengagement and
      secondary control coping. Physician perceptions of higher child primary control,
      and lower disengagement, were correlated with less parent-reported stress, better
      asthma control, and for primary control, fewer partial days of school missed.
      Physician reports were not correlated with child reports of coping, but physician
      reports of disengagement were correlated with child-reported conduct problems.
      DISCUSSION: Findings suggest that physician reports of child coping provide
      independent information from parent and child reports of coping, and could be
      leveraged to identify and intervene with patients who are at elevated risk for
      poor outcomes. (PsycINFO Database Record

PMID- 29172631
TI  - Different structural alterations in individual conduit arteries of SHRs compared
      to Wistar rats from the prehypertensive period to late adulthood.
AB  - Structural changes of thoracic aorta (TA), carotid (CA) and iliac artery (IA)
      were assessed in Wistar and spontaneously hypertensive rats (SHR) aged 3, 17, and
      52 weeks. Systolic blood pressure (sBP) was measured by plethysmography weekly.
      After perfusion fixation the arteries were processed for electron microscopy. The
      wall thickness (WT), cross-sectional area (CSA), inner diameter (ID), and WT/ID
      in all arteries and volume densities of endothelial cells (ECs), muscle cells
      (SMCs), and extracellular matrix (ECM) in TA were measured and their CSAs were
      calculated. In 3-week-old SHR compared to Wistar rats, sBP did not differ; in the
      TA, all parameters (WT, CSA, ID, WT/ID, CSA of SMCs, CSA of ECs, and CSA of ECM)
      were decreased; in CA, WT and CSA did not differ, ID was decreased, and WT/ID was
      increased; in IA, WT, CSA, and ID were increased. In 17- and 52-week-old SHRs,
      sBP and all parameters in all arteries were increased, only ID in IE in 52-week
      old SHRs and CSA of ECs in the TA in 17-week-old SHRs did not change.
      Disproportionality between BP increase and structural alterations during ontogeny
      in SHR could reflect the flexibility of the arterial tree to the different needs
      of supplied areas.

PMID- 29172632
TI  - Dual- and Polytobacco/Nicotine Product Use Trends in a National Sample of High
      School Students.
AB  - PURPOSE: The study purpose was to examine changes in patterns of ever and current
      dual- and polyproduct use over time and to examine demographic and modifiable
      risk factors including tobacco smoke exposure (TSE). DESIGN: A secondary analysis
      of the 2013 to 2015 National Youth Tobacco Survey data. SETTING: Nationwide high
      schools were selected. SUBJECTS: A total of 31 022 high school students.
      MEASURES: Ever and current (past 30 days) tobacco/nicotine product use, home
      tobacco/nicotine product use, TSE and e-cigarette vapor exposure, and demographic
      characteristics were measured. ANALYSIS: Multivariable logistic regression and
      multinomial logistic regression models. RESULTS: Of the students, 9.4% were ever
      dual users and 18.6% were ever poly users. Rates of ever/current use of e
      cigarettes and hookah increased from 2013 to 2015 (all Ps < .001). In 2015,
      participants were 4.8 times (95% confidence interval [CI], 4.5-5.2) and 4.0 times
      (95% CI, 3.5-4.4) more likely to report ever/current e-cigarette use and 1.61
      times (95% CI, 1.5-1.7) and 1.48 times (95% CI, 1.3-1.7) more likely to report
      ever/current hookah use. Participants reporting TSE were 15.4 times (95% CI, 11.5
      21.0) more likely to report current poly use, and those with e-cigarette exposure
      were 10.4 times (95% CI, 7.8-13.8) more likely to report current poly use.
      CONCLUSION: From 2013 to 2015, rates of ever and current use of e-cigarettes and
      hookah increased. Tobacco smoke and e-cigarette exposure were associated with
      higher rates of dual and poly use. Prevention efforts targeting these products
      are needed.

PMID- 29172633
TI  - Understanding the impact of adaptations to a parent-mediated intervention on
      parents' ratings of perceived barriers, program attributes, and intent to use.
AB  - Within the autism spectrum disorder field, rates of attrition in parent-mediated
      interventions have highlighted the need to engage families around improving the
      delivery of these services. The primary goal of this study was to approximate the
      impact of adaptations to an evidence-based, parent-mediated intervention, Project
      ImPACT (Improving Parents as Communication Teachers), that had been made in
      collaboration with families in a Medicaid system. A total of 103 parents of a
      child with autism spectrum disorder were randomized to watch a presentation of
      either the original or adapted Project ImPACT program. After watching the
      presentation, participants rated (1) demographic information, (2) perceived
      structural barriers, (3) Project ImPACT attributes, and (4) intent to use the
      program. Results from hierarchical linear regression models demonstrated that
      program type alone predicted parents' ratings of perceived structural barriers.
      Additionally, both program type and the interaction of program type and annual
      household income were unique predictors of parents' ratings of program attributes
      and intent to use. Qualitatively, although many parents reflected positively on
      both Project ImPACT programs, parents who viewed the adapted program appeared
      more likely to report positive program attributes. Results suggest the importance
      of engaging families in improving the fit of parent-mediated interventions for
      use within a variety of community settings.

PMID- 29172634
TI  - Primary genetic dystonia and first episode of psychosis.

PMID- 29172635
TI  - Midterm Clinical Results in Rugby Players Treated With the Bristow Procedure.
AB  - BACKGROUND: Although surgical shoulder stabilization by coracoid transfer is
      effective for collision athletes and has a low reinjury rate, no reports have
      described the midterm results of this procedure in specific patient cohorts of
      sufficient number or provided subjective assessments of these patients. PURPOSE:
      To evaluate midterm results after treatment of shoulder instability with the
      Bristow procedure in a large cohort of rugby players. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: This study included 176 shoulders of 152
      competitive rugby players who underwent shoulder stabilization surgery (Bristow
      procedure with Bankart repair) with a mean follow-up of 4 years (minimum of 2
      years) in our institute. The primary outcome measure was the difference in the
      presurgical and postsurgical functional Rowe score and Western Ontario Shoulder
      Instability index (WOSI) score and factors affecting these scores. Complication
      rates and associated factors were also investigated. RESULTS: In total, 176
      shoulders of 152 patients underwent the Bristow procedure with Bankart repair,
      and 93.2% of the players returned to their preinjury competition level at a mean
      of 6.3 months postoperatively. All Rowe and WOSI scores were significantly
      improved after surgery. The numbers of shoulders with functional failure as
      indicated by the Rowe score, WOSI score, and inability to return to the previous
      level of play were 28 (15.9%), 54 (30.7%), and 12 (6.8%), respectively. Multiple
      logistic regression analyses demonstrated that reinjury after surgery (odds ratio
      [OR] = 35.1) and the number of shoulder dislocations (OR = 11.2-11.4) negatively
      affected the competition level after return to play, while reinjury (OR = 11.1
      17.8), the number of shoulder subluxations (OR = 1.1-2.9), injury in the dominant
      shoulder (OR = 1.2-2.2), and large bone defects (OR = 1.1-11.5) negatively
      affected functional scores. Reinjury after shoulder stabilization occurred in 6
      of 176 shoulders (3.4%). Multiple logistic regression analysis demonstrated that
      reinjury after surgery occurred more frequently in players at lower versus higher
      grade levels of competition (OR = 21.0). Although differences were not
      significant, a trend was noted toward higher postoperative reinjury rates in
      forward players, those in the upper categories (professional and college), and
      those with injury in the nondominant shoulder. CONCLUSION: The Bristow procedure
      provides good midterm outcomes for competitive collision athletes, while
      postsurgical reinjury, the number of preoperative dislocations and subluxations,
      and large bone defects negatively affect postsurgical shoulder function. This
      information may be useful for treatment of shoulder dislocations in collision
      athletes.

PMID- 29172636
TI  - Patient and Provider Perspectives on a Mind-Body Program for Grieving Older
      Adults.
AB  - BACKGROUND: Spousal bereavement in older age is a major stressor associated with
      an increase in both mental and physical problems. The Stress Management and
      Resiliency Training: Relaxation Response Resiliency Program (SMART-3RP) is an 8
      week multimodal mind-body program that targets stress and has been found
      efficacious in decreasing the mental and physical manifestations of stress in
      varied populations. This qualitative study sought to investigate the relevance,
      credibility, and feasibility of the SMART-3RP in the community. METHODS: Focus
      groups were conducted among both older widowed adults and providers who support
      them in the community (eg, chaplains, hospice bereavement coordinators).
      Transcripts were coded independently by coders trained in qualitative research.
      Codebooks were created based on both general themes and detailed subthemes
      present in the transcripts. RESULTS: Findings from 4 focus groups revealed a
      general convergence between the needs of recently widowed older adults reported
      by widow(er)s and community providers alike and needs identified in the
      literature. Several components of the SMART-3RP target many of these needs (eg,
      social support, stress awareness, coping skills), making both community providers
      and widow(er)s report that the SMART-3RP is logical (89%) and would be helpful
      (100%) and successful in reducing symptoms (78%). Additionally, all widow(er)s
      reported a willingness to participate (100%). Feedback from the focus groups was
      used to adapt the SMART-3RP to improve its relevance to grief-related stress.
      CONCLUSIONS: Our findings suggest that the SMART-3RP may be helpful in decreasing
      somatic and psychological distress in older adults who have lost a spouse.

PMID- 29172637
TI  - Discrepancies Between the Supports Needed for Discharge of Patients With Terminal
      Cancer to Family Caregivers and What Supports Were Actually Provided in Japan:
      Assessment of Palliative Care Unit Nurses.
AB  - OBJECTIVES: Even if patients with terminal cancer hope to spend the rest of their
      lives at home, they are often unable to leave the hospital early due to their
      family caregivers' anxiety. This study aimed to investigate in Japan the
      discrepancies between the supports needed by and actually provided by palliative
      care unit nurses (PCUNs) to the family caregivers for discharge of patients with
      terminal cancer. METHODS: In this cross-sectional study, self-administered
      questionnaires including 6-point Likert-type scales assessing the reasons for
      difficulties in transition to home-based care were distributed to 1227 PCUNs.
      Using paired t tests, the differences between the scores on perceived importance
      and actual supports to family caregivers were examined. The supports actually
      provided were classified by factor analysis. The relationships between the PCUNs'
      characteristics and mean scores on the supports in each category were examined
      using multiple regression analysis. RESULTS: A total of 1023 (83.4%) completed
      questionnaires were returned. Scores on the actually provided supports for
      discharge to family caregivers were consistently and significantly lower than the
      corresponding scores on perceived importance for all 57 items ( P < .001). Factor
      analysis revealed that the supports actually provided to the family caregivers
      had a 4-factor structure. Multiple regression analyses revealed that gaining
      experience in palliative care, receiving necessary training, cooperating with
      palliative care staff, and cooperating with local service providers were
      significantly associated with higher levels of actual supply of supports to
      family caregivers. CONCLUSION: Our findings suggest that PCUNs need to be
      encouraged to provide further support to family caregivers for the discharge of
      patients with terminal cancer.

PMID- 29172638
TI  - The Survey of Favorite Interests and Activities: Assessing and understanding
      restricted interests in children with autism spectrum disorder.
AB  - Restricted interests are an established diagnostic symptom of autism spectrum
      disorder. While there is considerable evidence that these interests have
      maladaptive consequences, they also provide a range of benefits. This article
      introduces a new instrument, the Survey of Favorite Interests and Activities, and
      uses it to examine the nature of restricted interests in autism spectrum
      disorder. Respondents report substantial benefits of restricted interests as well
      as areas of difficulty. The Survey of Favorite Interests and Activities assesses
      Social Flexibility, Perseveration, Respondent Discomfort, Adaptive Coping, and
      Atypicality. All scales have Cronbach's alpha > 0.70. Age and socioeconomic
      status have little effect on Survey of Favorite Interests and Activities scales;
      nor does gender with the exception of interest Atypicality. The expected pattern
      of correlations with existing scales was found. Research and clinical
      implications are discussed.

PMID- 29172640
TI  - The art is in the delivery.

PMID- 29172641
TI  - Identification of Diagnostic Criteria for Chronic Hypersensitivity Pneumonitis:
      An International Modified Delphi Survey.
AB  - RATIONALE: Current diagnosis of chronic hypersensitivity pneumonitis (cHP)
      involves considering a combination of clinical, radiological, and pathological
      information in multidisciplinary team discussions. However, this approach is
      highly variable with poor agreement between centers. OBJECTIVES: We aimed to
      identify diagnostic criteria for cHP that reach consensus among international
      experts. METHODS: A 3-round modified Delphi survey was conducted between April
      and August 2017. Forty-five experts in interstitial lung disease from 14
      countries participated in the online survey. Diagnostic items included in round 1
      were generated using expert interviews and literature review. During rounds 1 and
      2, experts rated the importance of each diagnostic item on a 5-point Likert
      scale. The a priori threshold of consensus was >= 75% of experts rating a
      diagnostic item as very important or important. In the third round, experts
      graded the items that met consensus as important and provided their level of
      diagnostic confidence for a series of clinical scenarios. MEASUREMENTS AND MAIN
      RESULTS: Consensus was achieved on 18 of the 40 diagnostic items. Among these,
      experts gave the highest level of importance to the identification of a causative
      antigen, time relation between exposure and disease, mosaic attenuation on chest
      imaging, and poorly formed non-necrotizing granulomas on pathology. In clinical
      scenarios, the diagnostic confidence of experts in cHP was heightened by the
      presence of these diagnostic items. CONCLUSION: This consensus-based approach for
      the diagnosis of cHP represents a first step towards the development of
      international guidelines for the diagnosis of cHP.

PMID- 29172642
TI  - Comparison of automated volumetry of the hippocampus using NeuroQuant(r) and
      visual assessment of the medial temporal lobe in Alzheimer's disease.
AB  - Background Different clinically feasible methods for evaluation of medial
      temporal lobe atrophy exists and are useful in diagnostic work-up of Alzheimer's
      disease (AD). Purpose To compare the diagnostic properties of two clinically
      available magnetic resonance imaging (MRI)-based methods-an automated volumetric
      software, NeuroQuant(r) (NQ) (evaluation of hippocampus volume) and the Scheltens
      scale (visual evaluation of medial temporal lobe atrophy [MTA])-in patients with
      AD dementia, and subjective and mild cognitive impairment (non-dementia).
      Material and Methods MRIs from 56 patients (31 AD, 25 non-dementia) were assessed
      with both methods. Correlations between the methods were calculated and receiver
      operating curve (ROC) analyses that yield area under the curve (AUC) statistics
      were conducted. Results High correlations were found between the two MRI
      assessments for the total hippocampal volume measured with NQ and mean MTA score
      (-0.753, P < 0.001), for the right (-0.767, P < 0.001), and for the left (-0.675,
      P < 0.001) sides. The NQ total measure yielded somewhat higher AUC (0.88, "good")
      compared to the MTA mean measure (0.80, "good") in the comparison of patients
      with AD and non-dementia, but the accuracy was in favor of the MTA scale.
      Conclusion The two methods correlated highly and both methods reached equally
      "good" power.

PMID- 29172643
TI  - Prevalence and Characteristics of Interpersonal Violence in People Dying From
      Suicide in Victoria, Australia.
AB  - Victims of interpersonal violence are known to be at increased risk of suicidal
      ideation and attempts; however, few data exist on the impact that violence has on
      the risk of death from suicide. This study examined 2153 suicides (1636 males and
      517 females) occurring between 2009 and 2012. Information was sourced from the
      Coroners Court of Victoria's Suicide Register, a detailed database containing
      information on all Victorian suicides. Forty-two percent of women who died from
      suicide had a history of exposure to interpersonal violence, with 23% having been
      a victim of physical violence, 18% suffering psychological violence, and 16%
      experiencing sexual abuse. A large number of men who died from suicide had also
      been exposed to interpersonal violence, many of whom had perpetrated violence
      within the 6 weeks prior to their death. Targeted prevention, particularly
      removing barriers for men to seek help early after perpetrating violence is
      likely to have benefits in preventing suicide in both men and women.

PMID- 29172644
TI  - Combined thoracic and hepatobiliary surgery for iatrogenic bronchobiliary
      fistula.
AB  - Bronchobiliary fistula is a rare pathology mainly caused by hepatic tumors, bile
      duct obstruction, or hepatic hydatid disease. A 70-year-old man developed a
      bronchobiliary fistula after biliary stenting. After failure of conservative
      treatment including endoscopic retrograde biliary drainage, he underwent a
      combined operation with a two-level approach. Both a thoracotomy and laparotomy
      were performed, allowing pulmonary resection, diaphragmatic repair, and bile duct
      reconstruction during the same operation. Postoperative follow-up at one year
      showed optimal healing of the fistula.

PMID- 29172645
TI  - A Homogeneous Cell-Based Halide-Sensitive Yellow Fluorescence Protein Assay to
      Identify Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator
      Ion Channel.
AB  - Cystic fibrosis (CF), an inherited genetic disease, is caused by mutation of the
      Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes an
      ion channel involved in hydration maintenance by anion homeostasis. Ninety
      percent of CF patients possess one or more copies of the F508del CFTR mutation.
      This mutation disrupts trafficking of the protein to the plasma membrane and
      diminishes function of mature CFTR. Identifying small molecule modulators of
      mutant CFTR activity or biosynthesis may yield new tools for discovering novel CF
      treatments. One strategy utilizes a 384-well, cell-based fluorescence-quenching
      assay, which requires extensive wash steps, but reports sensitive changes in
      fluorescence-quenching kinetic rates. In this study, we describe the methods of
      adapting the protocol to a homogeneous, miniaturized 1,536-well format and
      further optimization of this functional F508del CFTR assay. The assay utilizes a
      cystic fibrosis bronchial epithelial (CFBE41o-) cell line, which was engineered
      to report CFTR-mediated intracellular flux of iodide by a halide-sensitive yellow
      fluorescence protein (YFP) reporter. We also describe the limitations of quench
      rate analysis and the subsequent incorporation of a novel, kinetic data analysis
      modality to quickly and efficiently find active CFTR modulators. This format
      yields a Z' value interval of 0.61 +/- 0.05. As further evidence of high
      throughput screen suitability, we subsequently completed a screening campaign of
      >645,000 compounds, identifying 2,811 initial hits. After completing secondary
      and tertiary follow-up assays, we identified 187 potential CFTR modulators, which
      EC50's < 5 MUM. Thus, the assay has integrated the advantages of a phenotypic
      screen with high-throughput scalability to discover new small-molecule CFTR
      modulators.

PMID- 29172646
TI  - 3,7-Dideazaneplanocin: Synthesis and antiviral analysis.
AB  - Objective To synthesize 3,7-dideazaneplanocin and evaluate its antiviral
      potential. Methods The target 3,7-dideazaneplanocin has been prepared in five
      steps from a readily available cyclopentenol. A thorough in vitro antiviral
      analysis was conducted versus both DNA and RNA viruses. Results A rational
      synthesis of 3,7-dideazaneplanocin was conceived and successfully pursued in such
      a way that it can be adapted to various analogs of 3,7-dideazaneplanocin. Using
      standard antiviral assays, no activity for 3,7-dideazaneplanocn was found.
      Conclusion Two structural features are necessary for adenine-based carbocyclic
      nucleosides (like neplanocin) for potential antiviral properties: (i) inhibition
      of S-adenosylhomocysteine hydrolase and/or (ii) C-5' activation via the mono
      nucleotide. These two requisite adenine structural features to fit these criteria
      are not present in in the target 3,7-dideazaneplanocin: (i) an N-7 is necessary
      for inhibition of the hydrolase and the N-3 is claimed to be essential for
      phosphorylation at C-5'. Thus, it is not surprising that 3,7-dideazaneplaoncin
      lacked antiviral properties.

PMID- 29172647
TI  - Clinical Utility of the Sport Concussion Assessment Tool 3 (SCAT3) Tandem-Gait
      Test in High School Athletes.
AB  - CONTEXT:   Dynamic balance during functional movement may provide important
      clinical information after concussion. The Sport Concussion Assessment Tool,
      version 3 (SCAT3), includes a timed tandem-gait test (heel-to-toe walking)
      administered with a pass-fail scoring system. Minimal evidence supports inclusion
      of the tandem-gait test in the SCAT3, especially in high school athletes.
      OBJECTIVE:   To determine (1) the percentage of healthy high school athletes who
      passed (best trial <=14 seconds) the tandem-gait test at baseline, (2) the
      association between sex and test performance (pass versus fail), and (3) the
      relationships among sex, age, height, and tandem-gait test score. DESIGN:   Cross
      sectional study. SETTING:   High school sports medicine center. PATIENTS OR OTHER
      PARTICIPANTS:   Two hundred athletes from 4 high schools (age = 15.8 +/- 1.2
      years, height = 170.3 +/- 10.3 cm, weight = 64.8 +/- 14.5 kg). MAIN OUTCOME
      MEASURE(S):   Healthy participants completed 4 trials of the SCAT3 tandem-gait
      test and a demographic questionnaire. Outcome measures were passing rate at
      baseline on the tandem-gait test and tandem-gait test score (time). RESULTS:  
      Overall, 24.5% (49/200) of participants passed the test. Sex and performance were
      associated (chi2 = 15.15, P < .001), with a passing rate of 38.6% (32/83) for
      males and 14.5% (17/117) for females. The regression model including predictor
      variables of sex and height, with the outcome variable of tandem-gait test score
      and time, was significant ( R2 = 0.20, P < .01). CONCLUSIONS:   Our findings
      suggest that the tandem-gait test had a high false-positive rate in high school
      athletes. Given that more than 75% of healthy participants failed the tandem-gait
      test, the 14-second cutoff appears to have limited clinical utility in the
      adolescent population. Functional movement deficits after concussion need to be
      accounted for, but the 14-second cutoff for the SCAT3 tandem-gait test does not
      appear to be an ideal way to assess these deficits in high school athletes.

PMID- 29172648
TI  - Prevention of Knee and Anterior Cruciate Ligament Injuries Through the Use of
      Neuromuscular and Proprioceptive Training: An Evidence-Based Review.
AB  - : Reference/Citation:  Donnell-Fink LA, Klara K, Collins JE, et al. Effectiveness
      of knee injury and anterior cruciate ligament tear prevention programs: a meta
      analysis. PLoS One. 2015;10(12)e0144063. CLINICAL QUESTION:   Is neuromuscular
      and proprioceptive training effective in preventing knee and anterior cruciate
      ligament (ACL) injuries? DATA SOURCES:   The authors searched CINAHL, Cochrane
      Central Register of Controlled Trials, MEDLINE/EMBASE, PubMed, and Web of Science
      databases from 1996 through December 2014 and limited the results to peer
      reviewed manuscripts published in English. Search terms for all databases were
      knee injury OR knee injuries; OR anterior cruciate ligament injury OR anterior
      cruciate ligament injuries; OR ACL injury OR ACL injuries; OR lower limb injury
      OR lower limb injuries AND prevention. STUDY SELECTION:   Inclusion criteria were
      (1) English language, (2) published from 1996 through 2014, (3) the intervention
      used neuromuscular or proprioceptive training to prevent knee or ACL injuries,
      (4) human participants, (5) the incidence of knee or ACL injury was provided.
      DATA EXTRACTION:   For the articles that met the inclusion criteria, 2 authors
      worked independently using the Jadad scale to extract the first author, year of
      publication, title, sport type, participant sex, participant age, country in
      which the study was conducted, number of participants in the control and
      intervention groups, intervention characteristics or components, and knee or ACL
      injury outcome. MAIN RESULTS:   A total of 24 studies with 1093 participants were
      included in this review. Intervention efficacy was determined from weighted
      incidence rate ratios. After the intervention of neuromuscular and proprioceptive
      training exercises, the incidence ratio (frequency of a disease or injury
      occurrence in a population over a specific time frame) was calculated at 0.731
      (95% confidence interval = 0.614, 0.871) for knee injury and at 0.493 (95%
      confidence interval = 0.285, 0.854) for ACL injury. This indicated a link between
      neuromuscular and proprioceptive training programs and injury reduction. No
      significant correlation was present between more components added to training and
      a greater decrease in injury to either the knee or ACL. CONCLUSIONS:  
      Neuromuscular and proprioceptive training appeared to decrease the incidence of
      injury to the knee and specifically the ACL. However, no evidence suggested that
      a specific group of exercises was better than others.

PMID- 29172649
TI  - Examining the Environmental Effects of Athletic Training: Perceptions of Waste
      and the Use of Green Techniques.
AB  - CONTEXT:   Environmental sustainability is a critical concern in health care.
      Similar to other professions, the practice of athletic training necessitates the
      use of a large quantity of natural and manufactured resources. OBJECTIVE:   To
      examine the perceptions of the waste produced by the practice of athletic
      training and the green practices currently used by athletic trainers (ATs) to
      combat this waste. DESIGN:   Mixed-methods study. SETTING:   Field setting.
      PATIENTS OR OTHER PARTICIPANTS:   A total of 442 ATs completed the study. Sixteen
      individuals participated in the qualitative portion. MAIN OUTCOME MEASURE(S):  
      Data from sections 2 and 3 of the Athletic Training Environmental Impact Survey
      were analyzed. Focus groups and individual interviews were used to determine
      participants' views of waste and the efforts used to combat waste. Descriptive
      statistics were used to examine types of waste. Independent t tests, chi2 tests,
      and 1-way analyses of variance were calculated to identify any differences
      between the knowledge and use of green techniques. Interviews and focus groups
      were transcribed verbatim and analyzed inductively. RESULTS:   Participants
      reported moderate knowledge of green techniques (3.18 +/- 0.53 on a 5-point
      Likert scale). Fifty-eight percent (n = 260) of survey participants perceived
      that a substantial amount of waste was produced by the practice of athletic
      training. Ninety-two percent (n = 408) admitted they thought about the waste
      produced in their daily practice. The types of waste reported most frequently
      were plastics (n = 111, 29%), water (n = 88, 23%), and paper for administrative
      use (n = 81, 21%). Fifty-two percent (n = 234) agreed this waste directly
      affected the environment. The qualitative aspect of the study reinforced
      recognition of the large amount of waste produced by the practice of athletic
      training. Types of conservation practices used by ATs were also explored.
      CONCLUSIONS:   Participants reported concern regarding the waste produced by
      athletic training. The amount of waste varies depending on practice size and
      setting. Future researchers should use direct measures to determine the amount of
      waste created by the practice of athletic training.

PMID- 29172651
TI  - International medical graduates: From America to 'down under'.

PMID- 29172650
TI  - Athletic Trainers' Attitudes and Perceptions of Environmental Sustainability.
AB  - CONTEXT:   Environmental sustainability efforts are becoming a critical concern
      in health care. However, little is known regarding how athletic trainers feel
      about the environment or what can be done to reduce the environmental impact of
      the practice of athletic training. OBJECTIVE:   To examine athletic trainers'
      attitudes toward and perceptions of factors related to environmental
      sustainability. DESIGN:   Sequential, mixed methods using a survey, focus groups,
      and personal interviews. SETTING:   Field study. PATIENTS OR OTHER PARTICIPANTS: 
      Four hundred forty-two individuals completed the survey. Sixteen participated in
      the qualitative portion. MAIN OUTCOME MEASURE(S):   Quantitative results from the
      Athletic Training Environmental Impact Survey included data from a 5-point Likert
      scale (1 = lowest rating and 5 = highest rating). Descriptive statistics and 1
      way analyses of variance were used to describe perceptions and determine
      differences in mean opinion, National Athletic Trainers' Association district,
      and use of green techniques. Qualitative data were transcribed verbatim and
      analyzed inductively. RESULTS:   The mean score for opinion of the environment
      was 3.30 +/- 0.52. A difference was found between opinion and National Athletic
      Trainers' Association district ( F9, 429 = 2.43, P = .01). A Bonferroni post hoc
      analysis identified this difference ( P = .03) between members of District 2
      (Delaware, New Jersey, New York, Pennsylvania) and District 9 (Alabama, Florida,
      Georgia, Kentucky, Louisiana, Mississippi, Tennessee). An inductive analysis
      resulted in 3 emergent themes: (1) barriers to using green techniques, (2)
      motivators for using green techniques, and (3) solutions to overcoming the
      barriers. The information gleaned from participants in the qualitative portion of
      the study can be useful for clinicians wishing to implement basic conservation
      efforts in their practice settings and may guide future sustainability projects.
      CONCLUSIONS:   Overall, participants reported a positive opinion of environmental
      sustainability topics related to athletic training. However, many barriers to
      practicing green techniques were identified.

PMID- 29172652
TI  - Association of Endocan, Ischemia-Modified Albumin, and hsCRP Levels With
      Endothelial Dysfunction in Type 2 Diabetes Mellitus.
AB  - We investigated the relationship of ischemia-modified albumin (IMA) and high
      sensitivity C-reactive protein (hsCRP) levels with direct (endocan) and indirect
      (carotid intima-media thickness [cIMT] and 24 hours urine protein excretion)
      endothelial dysfunction indicators in type 2 diabetes mellitus (T2DM). Patients
      with T2DM (n = 88) and 88 healthy individuals were included in the study. The
      median endocan (475.15 vs 216.37 pg/mL; P < .001, respectively) and hsCRP (10.74
      vs 3.11 mg/L; P < .001, respectively) and the mean IMA (0.64 +/- 0.12 vs 0.51 +/-
      0.12 absorbance units; P < .001, respectively) levels were higher in participants
      with endothelial dysfunction compared to those without endothelial dysfunction in
      T2DM. The 24-hour urine protein excretion and cIMT levels had a positive
      correlation with hsCRP ( r = .357; P = .001 and r = .592; P < .001,
      respectively), IMA ( r = .519; P < .001 and r = .495; P < .001, respectively) and
      endocan ( r = .347; P = .001 and r = .583; P < .001, respectively) levels in the
      T2DM group. Stepwise multivariable logistic regression analysis, which included
      laboratory findings found to be associated with endothelial dysfunction, showed
      that endocan (odds ratio [OR] = 1.456; P = .004), hsCRP (OR = 1.298; P = .008),
      and IMA (OR = 2.270, P = .003) were independent risk factors. It was found that
      none of these markers were superior in terms of diagnostic discrimination for
      endothelial dysfunction. Endocan, IMA, and hsCRP levels were found to be
      associated with endothelial dysfunction in patients with T2DM.

PMID- 29172653
TI  - Assessment of Relationship Between C-Reactive Protein to Albumin Ratio and
      Coronary Artery Disease Severity in Patients With Acute Coronary Syndrome.
AB  - The association of coronary artery disease (CAD) severity with increased C
      reactive protein (CRP) and decreased albumin levels has been reported. However,
      to our knowledge, no study has investigated the usefulness of the CRP to albumin
      ratio (CAR) in predicting intermediate-high SYNergy between Percutaneous Coronary
      Intervention with TAXus and cardiac surgery (SYNTAX) score (SS) and high SS II.
      Consecutive patients (n = 344) treated with percutaneous coronary intervention
      comprised the study population. The study population was divided into 2 groups
      according to SS >22 and mean SS II values, respectively. Patients with
      intermediate-high SS and high SS II had higher CAR than patients with low SS and
      SS II. History of diabetes mellitus, decreased albumin, lower left ventricular
      ejection fraction, and elevated CAR (odds ratio [OR]: 1.020; 95% confidence
      interval [CI], 1.009-1.031; P < .001) were independent predictors of high SS. The
      presence of hypertension, decreased hemoglobin and albumin levels, and increased
      CAR (OR: 1.014; 95% CI, 1.004-1.023; P < .001) were independent predictors of SS
      II. In receiver operating characteristic curve comparison, CAR was superior to
      CRP and albumin in prediction of intermediate-high SS, but only CRP in prediction
      of high SS II. The CAR calculated from the admission blood samples could be a
      useful parameter for predicting CAD severity using SS and SS II.

PMID- 29172654
TI  - Carotid-Femoral Pulse Wave Velocity in the Prediction of Cardiovascular Events
      and Mortality: An Updated Systematic Review and Meta-Analysis.
AB  - Arterial stiffness (AS) is a predictor of coronary artery outcomes in patients
      with cardiovascular disease (CVD). Carotid-femoral pulse wave velocity (cf-PWV)
      is a commonly used method for assessing AS. This study aimed to assess the
      relationship between cf-PWV and clinical CVD events. Of the 786 studies
      identified, 19 studies were included in the final meta-analysis. Meta-analysis
      revealed that participants with high cf-PWV by 1 standard deviation (SD), 1 m/s,
      and cutoff points have a high pooled relative risk for CVD events (1 SD: 1.25,
      95% confidence interval [CI]: 1.19-1.31; 1 m/s: 1.12, 95% CI: 1.07-1.18; and
      cutoff points: 1.80, 95% CI: 1.45-2.14) and CVD mortality (1 SD: 1.23, 95% CI:
      1.15-1.31; 1 m/s: 1.09, 95% CI: 1.04-1.14; and cutoff points: 1.85, 95% CI: 1.46
      2.24). In addition, we found that the predictive value of increased AS was higher
      in patients with higher disease risk for total CVD events and CVD mortality than
      in other patients. Carotid-femoral pulse wave velocity is a useful biomarker to
      improve the prediction of CV risk for patients and identify high-risk populations
      who may benefit from aggressive CV risk factor management.

PMID- 29172655
TI  - Association Between Platelet Indices and Inflammation in Patients With Stable
      Coronary Artery Disease.

PMID- 29172656
TI  - The Link Between Mean Platelet Volume to Lymphocyte Ratio and Complexity of
      Coronary Artery Disease.

PMID- 29172657
TI  - Editor's Choice-Effects of targeted temperature management on mortality and
      neurological outcome: A systematic review and meta-analysis.
AB  - AIMS: The purpose of this study was to conduct a systematic review, and where
      applicable meta-analyses, examining the evidence underpinning the use of targeted
      temperature management following resuscitation from cardiac arrest. METHODS AND
      RESULTS: Multiple databases were searched for publications between January 2000
      February 2016. Nine Population, Intervention, Comparison, Outcome questions were
      developed and meta-analyses were performed when appropriate. Reviewers extracted
      study data and performed quality assessments using Grading of Recommendations,
      Assessment, Development and Evaluation methodology, the Cochrane Risk Bias Tool,
      and the National Institute of Health Study Quality Assessment Tool. The primary
      outcomes for each Population, Intervention, Comparison, Outcome question were
      mortality and poor neurological outcome. Overall, low quality evidence
      demonstrated that targeted temperature management at 32-36 degrees C, compared to
      no targeted temperature management, decreased mortality (risk ratio 0.76, 95%
      confidence interval 0.61-0.92) and poor neurological outcome (risk ratio 0.73,
      95% confidence interval 0.60-0.88) amongst adult survivors of out-of-hospital
      cardiac arrest with an initial shockable rhythm. Targeted temperature management
      use did not benefit survivors of in-hospital cardiac arrest nor out-of-hospital
      cardiac arrest survivors with a non-shockable rhythm. Moderate quality evidence
      demonstrated no benefit of pre-hospital targeted temperature management
      initiation. Low quality evidence showed no difference between endovascular versus
      surface cooling targeted temperature management systems, nor any benefit of
      adding feedback control to targeted temperature management systems. Low quality
      evidence suggested that targeted temperature management be maintained for 18-24
      h. CONCLUSIONS: Low quality evidence supports the in-hospital initiation and
      maintenance of targeted temperature management at 32-36 degrees C amongst adult
      survivors of out-of-hospital cardiac arrest with an initial shockable rhythm for
      18-24 h. The effects of targeted temperature management on other populations, the
      optimal rate and method of cooling and rewarming, and effects of fever require
      further study.

PMID- 29172659
TI  - [Miscellaneous].

PMID- 29172658
TI  - [Tetrahydrobiopterin (BH4) deficiency - diagnosis and treatment].
AB  - Since the initial breaking discovery of Folling that the severe neurological
      consequences of phenylketonuria could be prevented by use of low phenylalanine
      (Phe) diet, it has been shortly recognised that defective phenylalanine
      metabolism may also arise from the deficiency of tetrahydrobiopterin (BH4)
      cofactor, required for phenylalanine-hydroxylase activity. Furthermore, as BH4 is
      in Phe metabolism, it is also a cofactor for the activities of tyrosine
      hydroxylase and tryptophane hydroxylase, enzymes required for the synthesis of
      catecholamines and serotonin neurotransmitters. Besides hyperphenylalaninemia in
      patients with tetrahydrobiopterin deficiencies, dopamine and serotonin
      deficiencies, with different disorders of the central nervous system also
      develop. Mild form of tetrahydrobiopterin deficiency is rare, most of the
      patients have severe neurological abnormalities including progressive mental
      retardation if not treated properly. Early diagnosis and treatment are essential
      and can improve the clinical course and prognosis. Orv Hetil. 2017; 158(48): 1897
      1902.

PMID- 29172660
TI  - [Diagnostics of inborn errors of metabolism: laboratory approaches].
AB  - Inherited errors of metabolism are rare genetic disorders characterized by
      diverse clinical and biochemical phenotypes. The complexity of signs and symptoms
      often presents a challenge for both clinicians and laboratory specialists. In
      many cases, prevention of permanent neurological symptoms or death in patients
      presenting these disorders is dependent on early diagnosis and introduction of
      appropriate therapy. For professionals it is indispensable to be familiar with
      the major clinical signs of inborn errors of metabolism and with the necessary
      and available laboratory studies to achieve an early diagnosis. The review tries
      to give a way of approach, diagnostic algorithm of laboratory measurements for
      the correct diagnosis in inherited errors of metabolism. The combination of
      biochemical and clinical signs, results of special metabolic investigations
      represent a portentous challenge in general practice. For the correct diagnosis
      of an inherited error of metabolism, the teamwork between clinicians and
      laboratory specialists is indispensable. Orv Hetil. 2017; 158(48): 1903-1907.

PMID- 29172661
TI  - [Novelties in the treatment of pediatric immune thrombocytopenia - 2017].
AB  - Immune thrombocitopenia in children is a very variable disease. International
      recommendations give therapeutic possibilities without strong protocols. In 2011,
      a therapeutic algorithm was published based on Hungarian practice. Recently, new
      innovative drugs have been available even in Hungary, so there is a need for
      modification of the therapeutic protocols. In this summary we give an overview
      about the current up-to-date management. In infancy and in childhood, high-dose
      immunglobulin treatment is recommended henceforward. In older children an
      alternative can be steroid therapy (pulses or long-term low-dose treatment). In
      resistant cases, a new thrombopoetin receptor stimulant, eltrombopag can be
      administered. This drug is registered in Hungary, and can very effectively
      influence the prognosis. Splenectomy is very rare nowadays in children. Immune
      thrombocytopenia is an unpredictable disease. Cure rate is about 70-80% of the
      cases, but management of the patients needs special care and specialist. Orv
      Hetil. 2017; 158(48): 1891-1896.

PMID- 29172662
TI  - [Maternal and neonatal vitamin B12 deficiency detected by expanded newborn
      screening].
AB  - INTRODUCTION: Infant vitamin B12 deficiency can manifest as a severe
      neurodegenerative disorder and is usually caused by maternal deficiency due to
      vegetarian diet or pernicious anaemia. Its early recognition and treatment can
      prevent potentially serious and irreversible neurologic damage. Biochemically,
      vitamin B12 deficiency leads to an accumulation of methylmalonic acid,
      homocysteine, and propionylcarnitine. Expanded newborn screening using tandem
      mass spectrometry may identify neonatal and maternal vitamin B12 deficiency by
      measurement of propionylcarnitine and other metabolites in the dried blood spot
      sample of newborns. AIM: To summarize our experiences gained by screening for
      vitamin B12 deficiency. METHOD: Clinical and laboratory data of vitamin B12
      deficient infants diagnosed in Szeged Screening Centre were retrospectively
      analysed. RESULTS: In Hungary, expanded newborn screening was introduced in 2007.
      Since then approximately 395 000 newborns were screened in our centre and among
      them, we identified four newborns with vitamin B12 deficiency based on their
      screening results. In three cases an elevated propionylcarnitine level and in the
      fourth one a low methionine level were indicative of vitamin B12 deficiency. We
      also detected an additional vitamin B12-deficient infant with neurological
      symptoms at 4 months of age, after a normal newborn screening, because of
      elevated urinary methylmalonic acid concentration. Vitamin B12 deficiency was
      secondary to maternal autoimmune pernicious anaemia in all the five infants. As a
      result of the recognized cases the incidence of infant vitamin B12 deficiency in
      the East-Hungarian region was 1.26/100 000 births, but the real frequency may be
      higher. Conslusions: Optimizing the cut off values of current screening
      parameters and measuring of methylmalonic acid and/or homocysteine in the dried
      blood spot, as a second tier test, can improve recognition rate of vitamin B12
      deficiency. Orv Hetil. 2017; 158(48): 1909-1918.

PMID- 29172663
TI  - Characterization of mercury-induced stress biomarkers in Fagopyrum tataricum
      plants.
AB  - The effect of mercury stress on antioxidant enzymes, lipid peroxidation,
      photosynthetic pigments, hydrogen peroxide content, osmolytes, and growth
      parameters in Tartary buckwheat were investigated. The effect of Hg-exposure was
      found to be time (15 and 30 days) and concentration (0, 25, 50, and 75 MUM)
      dependent. Hg was readily absorbed by seedlings with higher content in roots and
      it resulted in reduction of root and shoot length. The root and shoot Hg uptakes
      were significantly and directly correlated with each other. However, the fresh
      mass and biomass increased up to 50 MUM Hg-treatment at both time periods. A
      significant positive correlation was observed between biomass accumulation with
      relative water content. Hg levels were positively correlated with the production
      of hydrogen peroxide in leaves as evidenced by 3, 3-diaminobenzidine (DAB)
      mediated tissue fingerprinting. The osmolyte levels in general were elevated
      except for proline and protein which showed a decline at 75 MUM Hg-treatment at
      30-days. Amongst the photosynthetic pigments, chlorophyll showed a decline while
      as carotenoid and anthocyanin levels were elevated. The activity of antioxidant
      enzymes such as ascorbate peroxidase (APX), guaiacol peroxidase (POD),
      glutathione reductase (GR), Glutathione-s-transferase (GST) and superoxide
      dismutase (SOD) were positively correlated with Hg-treatment except SOD, which
      declined at 75 MUM Hg-treatment in 30-days old seedlings. Catalase (CAT) activity
      showed a positive correlation up to 50 MUM Hg-treatment but at 75 MUM Hg-stress
      it decreases at both 15 and 30 days.

PMID- 29172664
TI  - Knowledge, Activation, and Costs of the Pharmacists' Pneumonia Prevention Program
      (PPPP): A Novel Senior Center Model to Promote Vaccination.
AB  - BACKGROUND: Vaccination is the best way to prevent pneumococcal disease (PD), but
      40% of older adults remain unvaccinated nationwide, with even greater
      nonvaccination rates among African Americans (AAs). Prior studies suggest that
      insufficient knowledge contributes to low vaccination rates. The Pharmacists'
      Pneumonia Prevention Program (PPPP) was designed to improve older adults'
      knowledge about PD and pneumococcal vaccination (PV). OBJECTIVE: To measure
      PPPP's effect on knowledge and activation in a predominantly AA population and
      determine program costs. METHODS: PPPP uses a senior center model with a
      pharmacist presentation, actors' skit, and small-group action planning. Knowledge
      about PD risk, transmission, symptoms, and PV side effects was assessed at
      baseline (BL), postintervention (PT), and 3 months (M3) and analyzed using an
      intention-to-treat (ITT) approach. Actions taken (got vaccinated, spoke to doctor
      or pharmacist, discussed with family/friends) were assessed at M3. PPPP costs
      ($US 2013) included staff time, PV, actor, and site fees. RESULTS: Of 276
      attending PPPP, 190 consented and were included in the ITT sample, which was
      largely black (80.5%) and female (76.3%) and had a mean age of 74.4 years.
      Knowledge improved by 46.8% (BL vs PT), with significant gains in all domains. At
      M3, knowledge improved by 54.2% vs BL, indicating sustained gains; 37.2% of
      previously unvaccinated participants reported receiving PV by M3. Program cost
      was $119 per attendee. CONCLUSION: PPPP significantly improved PD and PV
      knowledge. It could be delivered more efficiently by holding larger events on
      fewer dates, staffing with volunteers where appropriate, and utilizing a local
      pharmacy to manage the vaccine supply.

PMID- 29172665
TI  - Group analysis identifies differentially elevated biomarkers with distinct
      outcomes for advanced acute kidney injury in cardiac surgery.
AB  - AIM: To investigate early postoperative biomarkers for risk discrimination of
      advanced acute kidney injury (AKI). MATERIALS & METHODS: Postoperative plasma
      biomarkers including NGAL, h-FABP, CK-MB, hsTNT, NT-proBNP, IL-6, IL-10 and VEGF
      were analyzed using group-based method among 426 patients with AKI after cardiac
      surgery. RESULTS: Six patient groups with distinct biomarker patterns were
      identified. Individual biomarker displayed significant difference across the
      groups. The groups showed better discrimination for advanced AKI than any single
      biomarker either with or without adjusting for clinical variables. Average
      concentration of a single biomarker within each group, mortality and risk of a
      secondary outcome all demonstrated an approximately U-shaped relationship with
      proportion of advanced AKI within each group. CONCLUSION: The group-based
      analysis revealed that the order of the patient groups with an increasing
      likelihood of advanced AKI had a nonlinear relationship with average
      concentration of an individual biomarker, mortality and risk of other outcomes.

PMID- 29172666
TI  - Association of 2,4-dichlorophenol urinary concentrations and olfactory
      dysfunction in a national sample of middle-aged and older U.S. adults.
AB  - Olfaction is a key sensory mechanism in humans. Deficits in this chemosensory
      function have wide-ranging impacts on overall health and quality of life. This
      study examines the role of environmental phenols as risk factors for olfactory
      dysfunction among a random sample of 839 middle-aged and older U.S. adults.
      Olfactory function assessment was carried out using a short 8-item test, scores
      on which were used to classify subjects into normal or impaired olfactory
      function groups. Logistic regression models were used to test for associations
      between olfactory impairment and creatinine-adjusted urinary levels of 8 common
      environmental phenols, adjusting for potentially confounding covariates. A
      statistically significant association between 2,4-dichlorophenol levels and
      olfactory impairment (OR = 1.02 [95 % CI: (1.003, 1.04)]; p = 0.02) was found.
      2,4-dichlorophenol is a hazardous pollutant with widespread exposure via
      industrial and indoor air pollution, diet, and the use of pesticides and
      herbicides. This study is the first to reveal its role in olfactory impairment.

PMID- 29172667
TI  - Reflections on the history of bareback sex through ethnography: the works of
      subjectivity and PrEP.
AB  - Throughout the history of bareback sex (condomless sex between men), 'subjects'
      have been created, particularly through scientific literature, to characterise
      the men who engage in the sexual practice. For example, a gay man who does not
      use a condom may be framed as a pathologised subject. This paper first presents
      this history. Afterwards, by relying upon ethnographic data such as interviews
      collected from fieldwork research done in Toronto in 2014 with young gay men who
      have bareback sex, it shows exactly how these young gay men related themselves to
      those subjects. Then, it focuses on the pre-exposure prophylaxis (PrEP) Truvada
      as a new HIV prevention technology. Although PrEP can allow condomless sex to
      occur while diminishing the risk of HIV transmission, at the time of the
      research, none of the young gay men were interested in using this tool despite
      being the subjects for whom the drug is tailored. This paper argues that PrEP and
      subjectivity are coproduced and can have conflicting meanings. This contradiction
      of meanings is a result of the various representations and symbols of bareback
      sex and the men who engage in the practice that have been produced throughout the
      history of bareback sex.

PMID- 29172668
TI  - Symmetrical Parameterization of Rigid Body Transformations for Biomolecular
      Structures.
AB  - Assessing preferred relative rigid body position and orientation is important in
      the description of biomolecular structures (such as proteins) and their
      interactions. In this article, we extend and apply the "symmetrical
      parameterization," which we recently introduced in the kinematics community, to
      address problems in structural biology. We also review parameterization methods
      that are widely used in structural biology to describe relative rigid body
      motions (in particular, orientations) as a basis for comparison. The new
      symmetrical parameterization is useful in describing the relative biomolecular
      rigid body motions, where the parameters are symmetrical in the sense that the
      subunits of a complex biomolecular structure are described in the same way for
      the corresponding motion and its inverse. The properties of this new
      parameterization, singularity analysis, and inverse kinematics are also
      investigated in more detail. Finally, parameterization is applied to real
      biomolecular structures and a potential application to structure modeling of
      symmetric macromolecules to show the efficacy of the symmetrical parameterization
      in the field of computational structural biology.

PMID- 29172669
TI  - Long-term Effect of Injection Treatment for Osteoarthritis in the Knee by
      Orthokin Autologous Conditioned Serum.
AB  - Background Orthokin is an intra-articular autologous conditioned serum (ACS). Its
      use might have a beneficial biological effect on pain and function of
      osteoarthritis in the knee. However, earlier studies lack any consensus on its
      clinical application and disease modifying effect. Objective The aim of this
      study was to investigate the long-term effect of Orthokin injection treatment on
      prevention of surgical treatment for end-stage knee osteoarthritis. Study Design
      Prospective cohort study. Methods Patients of the previously published Orthokin
      cohort were contacted to determine whether any intra-articular surgical
      intervention or osteotomy of the study knee had taken place during the past
      decade. A log-rank test was performed to evaluate the differences in the survival
      distribution for the 2 types of intervention: Orthokin versus placebo. Results
      The survival distributions for the 2 interventions were not statistically
      significantly different, chi2(1) = 2.069, P = 0.150. After 7.5 +/- 3.9 years,
      46.3% of the placebo and 40.3% of the Orthokin group had been treated surgically.
      Conclusion The use of Orthokin in knee osteoarthritis patients did not result in
      a delay regarding surgical treatment. Clinical Relevance The intra-articular use
      of Orthokin does not seem to prevent or delay surgical intervention at 10 years
      after treatment for end-stage knee osteoarthritis.

PMID- 29172670
TI  - Predicting tuberculosis treatment outcome using metabolomics.
AB  - AIM: Predicting a poor treatment outcome would offer significant benefits for
      patient care and for new drug development. Materials, methods & results: Urine
      samples from tuberculosis-positive patients with a successful and unsuccessful
      treatment outcome were collected at baseline and analyzed. The identified
      metabolites were used in a forward logistic regression model, which achieved a
      receiver operating characteristic area under the curve of 0.94 (95% CI: 0.84-1)
      and cross-validated well in a leave-one-out context, with an area under the curve
      of 0.89 (95% CI: 0.7-1). Two possible predictors were identified, which are
      associated with a gut microbiota imbalance. DISCUSSION & CONCLUSION: Our findings
      show the capacity of metabolomics to predict treatment failure at the time of
      diagnosis, which potentially offers significant benefits for the use in new drug
      development clinical trials and individualized patient care.

PMID- 29172672
TI  - platelet-lymphocyte ratio in prediction of outcome of acute heart failure.
AB  - AIM: To examine the role of the ratios of platelet or neutrophil to lymphocyte
      count (PLR or NLR) in predicting hospital death and long-term mortality in acute
      heart failure (AHF). Methods & materials: The records of 554 admissions from 354
      patients discharged from VAWNY with AHF between 2011 and 2015 were reviewed. The
      associations between admission PLR or NLR and hospital and long-term mortality
      were assessed by univariate and multivariate analyses. RESULTS: PLR was similar
      regarding hospital mortality. Long-term mortality was higher in the third tertile
      PLR (PLR >210; p = 0.034). Neither PLR nor NLR was an independent predictor of
      mortality. CONCLUSION: Although higher PLR was associated with long-term
      mortality, it failed to independently predict the prognosis of AHF.

PMID- 29172673
TI  - How Informative Are Self-Reported Adult Attention-Deficit/Hyperactivity Disorder
      Symptoms? An Examination of the Agreement Between the Adult Attention
      Deficit/Hyperactivity Disorder Self-Report Scale V1.1 and Adult Attention
      Deficit/Hyperactivity Disorder Investigator Symptom Rating Scale.
AB  - OBJECTIVES: Assess agreement between self-ratings via the adult attention
      deficit/hyperactivity disorder (ADHD) Self-Report Scale (ASRS)-v1.1 Symptom
      Checklist and clinician ratings via the adult ADHD Investigator Symptom Rating
      Scale (AISRS) expanded version using DSM-5 adult ADHD patients (referred sample)
      and ADHD controls (recruited from a primary care physician practice). METHODS:
      The ASRS v1.1 Symptom Checklist was administered to measure self-reported ADHD
      symptoms and impairment, the Adult ADHD Clinical Diagnostic Scale v1.2 was used
      to establish an adult ADHD diagnosis and the childhood and adult/current sections
      of the scale were used to provide scores to measure symptoms of childhood ADHD
      and recent symptoms of adult ADHD, the AISRS to measure ADHD current symptom
      severity. RESULTS: Participants (n = 299; range 18-58), of which 171 were ADHD+
      and 128 ADHD-. ASRS and AISRS total scores and individual subsections examining
      inattention, hyperactivity, emotional dysfunction (EF), and emotional dyscontrol
      (EC) were all significantly correlated (Spearman's rho's = 0.78-0.89, ps < 0.01).
      Correlations remained significant when controlling for demographic factors and
      psychiatric conditions. CONCLUSIONS: The ASRS (self) and AISRS (clinician rated)
      scales have high agreement. This agreement extended not only the to the core 18
      DSM symptoms, but also to the additional 13 symptoms that examine EC and EF.

PMID- 29172671
TI  - Pulmonary quantitative CT imaging in focal and diffuse disease: current research
      and clinical applications.
AB  - The frenetic development of imaging technology-both hardware and software
      provides exceptional potential for investigation of the lung. In the last two
      decades, CT was exploited for detailed characterization of pulmonary structures
      and description of respiratory disease. The introduction of volumetric
      acquisition allowed increasingly sophisticated analysis of CT data by means of
      computerized algorithm, namely quantitative CT (QCT). Hundreds of thousands of
      CTs have been analysed for characterization of focal and diffuse disease of the
      lung. Several QCT metrics were developed and tested against clinical, functional
      and prognostic descriptors. Computer-aided detection of nodules, textural
      analysis of focal lesions, densitometric analysis and airway segmentation in
      obstructive pulmonary disease and textural analysis in interstitial lung disease
      are the major chapters of this discipline. The validation of QCT metrics for
      specific clinical and investigational needs prompted the translation of such
      metrics from research field to patient care. The present review summarizes the
      state of the art of QCT in both focal and diffuse lung disease, including a
      dedicated discussion about application of QCT metrics as parameters for clinical
      care and outcomes in clinical trials.

PMID- 29172674
TI  - Single nucleotide polymorphisms in TNF are associated with susceptibility to
      aspirin-exacerbated respiratory disease but not to cytokine levels: a study in
      Mexican mestizo population.
AB  - AIM: To evaluate the association of three single nucleotide polymorphisms in TNF
      and one in LTA in Mexican patients with aspirin-exacerbated respiratory disease
      (AERD) and the correlation of those single nucleotide polymorphisms with serum
      levels of TNF-alpha. PATIENTS & METHODS: Case-control study including 133
      patients with AERD, 135 patients with asthma (aspirin-tolerant asthmatics) and
      182 healthy subjects. RESULTS: GA genotype of rs1800629 in TNF was found to be
      associated with the risk of developing AERD (p < 0.05; odds ratio = 2.36) and by
      dominant model (p < 0.05; odds ratio = 2.51). Furthermore, there was a difference
      in the serum levels between the aspirin-tolerant asthmatics group and the other
      groups (p < 0.001). CONCLUSION: The GA genotype of rs1800629 is associated with
      genetic susceptibility to AERD, but it does not correlate to protein serum
      levels.

PMID- 29172675
TI  - Immune-related tumour response assessment criteria: a comprehensive review.
AB  - Growing emphasis on precision medicine in oncology has led to increasing use of
      targeted therapies that encompass a spectrum of drug classes including
      angiogenesis inhibitors, immune modulators, signal transduction inhibitors, DNA
      damage modulators, hormonal agents etc. Immune therapeutic drugs constitute a
      unique group among the novel therapeutic agents that are transforming cancer
      treatment, and their use is rising. The imaging manifestations in patients on
      immune therapies appear to be distinct from those typically seen with
      conventional cytotoxic therapies. Patients on immune therapies may demonstrate a
      delayed response, transient tumour enlargement followed by shrinkage, stable
      size, or initial appearance of new lesions followed by stability or response.
      These newer patterns of response to treatment have rendered conventional criteria
      such as World Health Organization and response evaluation criteria in solid
      tumours suboptimal in monitoring changes in tumour burden. As a consequence,
      newer imaging response criteria such as immune-related response evaluation
      criteria in solid tumours and immune-related response criteria are being
      implemented in many trials to effectively monitor patients on immune therapies.
      In this review, we discuss the traditional and new imaging response criteria for
      evaluation of solid tumours, review the outcomes of various articles which
      compared traditional criteria with the new immune-related criteria and discuss
      pseudo-progression and immune-related adverse events.

PMID- 29172676
TI  - Effects of conditioning time and sodium bentonite on pellet quality, growth
      performance, intestinal morphology and nutrient retention in finisher broilers.
AB  - 1. This study was carried out to evaluate the effect of steam-conditioning time
      and different levels of processed sodium bentonite (PSB) on pellet quality,
      growth performance, intestinal development and morphology, and nutrient
      digestibilities in broilers during finisher period (d 24-45). 2. A total of 810
      male chicks were reared in commercial conditions on floor pens till d 24. Then,
      birds were weighed and used in a completely randomised design experiment with a 3
      * 3 factorial arrangement, including three levels of conditioning times (0, 2 and
      4 min) and three PSB levels (0, 7.5 and 15 g/kg diet). Each of the 9 diets fed to
      6 replicates group of 15 birds each. 3. The results showed that 2-min steam
      conditioning and 15 g/kg PSB supplementation significantly increased pellet
      durability index (PDI) and hardness, and decreased electrical consumption of
      pelleting. Diets had no significant effects on body weight, feed intake and feed
      conversion ratio. Although dietary treatments did not influence relative weight
      and length of three segments of small intestine, 2-min steam conditioning
      significantly improved villus height (VH) and crypt depth. Steam conditioning of
      diet for 2 min significantly increased apparent metabolisable energy (AME), ether
      extract (EE), calcium (Ca) and dry matter (DM) retention in birds measured during
      38-42 d of age. 4. It could be concluded that 2-min steam conditioning improved
      PDI and hardness, VH and nutrient retention (AME, EE, Ca and DM), but did not
      affect growth performance in broilers during finisher period.

PMID- 29172678
TI  - Commentary: how will interventional oncology navigate the "valleys of death" for
      new medical devices?
AB  - Whereas clinical trials of cancer drugs have methodological standards and
      conventional primary endpoints, these are not necessarily applicable to the
      clinical development of loco-regional treatments and new medical devices. The
      current challenge is to generate high-level clinical evidence for loco-regional
      treatments to define the benefits for patients. In this article, we argue that,
      to generate convincing evidence of clinical efficacy and safety, the collective
      coherence of the entire data package is often more important than the primary
      endpoint of one clinical trial. We also propose that, when a comprehensive
      clinical data package is not feasible, limited clinical data can be supplemented
      with other types of evidence. Emerging life science companies often define the
      "valley of death" after securing initial investment to translate an early medical
      device concept to a development stage that is attractive to funders.
      Unfortunately for this industry, there is a second "valley of death" if the focus
      and goal is only regulatory approval, to the neglect of clinical acceptance and
      reimbursement. For the emerging specialism of interventional oncology, it is
      critical to plan a clear line of sight for each new medical device to avoid the
      valleys of death and to demonstrate the clinical benefit. Increased international
      guidance to establish realistic yet convincing standards in this area may avoid
      attrition of potentially beneficial devices and therapeutic procedures in the
      valleys of death.

PMID- 29172679
TI  - In Silico Approach to Investigate the Structural and Functional Attributes of
      Familial Hypercholesterolemia Variants Reported in the Saudi Population.
AB  - Familial hypercholesterolemia (FH) is a metabolic disorder that leads primarily
      to premature cardiovascular diseases, the main cause of mortality in Saudi Arabia
      (SA). FH is underreported and underdiagnosed in SA with statistical evidence of
      high expected prevalence in such a consanguineous community. Lacking knowledge of
      which and how these alterations are actually impacting lipid metabolism is one of
      the main reasons why FH is insufficiently diagnosed in the region. The aim of
      this study was to develop a fast prediction approach using an integrated
      bioinformatics method for future screening of the potential causative variants
      from national registries. A total of 21 variants were detected with majority rate
      in LDLR (81%). Variants were classified based on the type of mutation. Missense
      variants resulting in amino acid changes, c.1429G>A (p.D477N), c.1474G>A
      (p.D492N), c.1731G>T (p.W577C), and c.1783C>T (p.R595W) in LDLR gene, in addition
      to c.9835A>G (p.S3279G) in APOB, were shown to be deleterious by concordant
      analysis. Furthermore, functional interaction deformities showed a significant
      loss and gain of energies in the mutated proteins. These findings will help in
      distinguishing the most harmful mutations needed to be screened for clinically
      diagnosed FH patients in SA. Such computational research is necessary to avoid
      time consumption and the usage of expensive biological experiments. This can be a
      fast track to facilitate the future filtering and screening of causative
      mutations from national registries.

PMID- 29172680
TI  - Efficacy and Safety of HLD200, Delayed-Release and Extended-Release
      Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: Evening-dosed HLD200 is a delayed-release and extended-release
      methylphenidate (DR/ER-MPH) formulation consisting of uniform, dual-layered
      microbeads with an inner drug-loaded core. DR/ER-MPH is designed to delay the
      initial release of drug by 8-10 hours, and thereafter, provide a controlled,
      extended drug release to target onset of effect upon awakening that lasts into
      the evening. This phase 3 study evaluated the safety and efficacy of DR/ER-MPH on
      symptoms and temporal at-home functional impairment in children with attention
      deficit/hyperactivity disorder (ADHD). METHODS: This 3-week, randomized, double
      blind, multicenter, placebo-controlled, parallel-group, forced-dose titration
      trial evaluated DR/ER-MPH (40-80 mg/day) in children aged 6-12 years with ADHD.
      Primary efficacy endpoint was the ADHD rating scale-IV (ADHD-RS-IV), and the key
      secondary endpoints were the Before-School Functioning Questionnaire (BSFQ), and
      Parent Rating of Evening and Morning Behavior-Revised, morning (PREMB-R AM) and
      evening (PREMB-R PM). Safety measures included spontaneously reported treatment
      emergent adverse events (TEAEs) and two TEAEs of special interest, appetite
      suppression and insomnia (with direct questioning on sleep disturbance). RESULTS:
      One hundred sixty-one participants were included in the intent-to-treat
      population (DR/ER-MPH, n = 81; placebo, n = 80). After 3 weeks, DR/ER-MPH
      achieved significant improvements versus placebo in ADHD symptoms (least-squares
      [LS] mean ADHD-RS-IV: 24.1 vs. 31.2; p = 0.002), and at-home early morning (LS
      mean BSFQ: 18.7 vs. 28.4; p < 0.001; LS mean PREMB-R AM: 2.1 vs. 3.6; p < 0.001)
      and late afternoon/evening (LS mean PREMB-R PM: 9.4 vs. 12.2; p = 0.002)
      functional impairment. Commonly reported TEAEs (>=10%) were insomnia and
      decreased appetite. CONCLUSIONS: DR/ER-MPH was generally well tolerated and
      demonstrated significant improvements versus placebo in ADHD symptoms and at-home
      functional impairments in the early morning, late afternoon, and evening in
      children with ADHD.

PMID- 29172681
TI  - Further Analysis of the Predictive Effects of a Free-Operant Competing Stimulus
      Assessment on Stereotypy.
AB  - We conducted five experiments to evaluate the predictive validity of a free
      operant competing stimulus assessment (FOCSA). In Experiment 1, we showed that
      each participant's repetitive behavior persisted without social consequences. In
      Experiment 2, we used the FOCSA to identify high-preference, low-stereotypy (HP
      LS) items for 11 participants and high-preference, high-stereotypy (HP-HS) items
      for nine participants. To validate the results of the FOCSAs (Experiment 3), we
      used a three-component multiple schedule to evaluate the immediate and subsequent
      effects of an HP-LS stimulus, an HP-HS stimulus, or both (in separate test
      sequences) on each participant's stereotypy. Results of Experiment 3 showed that
      the FOCSA correctly predicted the immediate effect of the HP-LS stimulus for 10
      of 11 participants; however, the FOCSA predictions were less accurate for the HP
      HS stimulus. Results of Experiment 4 showed that a differential reinforcement of
      other behavior procedure in which participants earned access to the HP-LS for
      omitting vocal stereotypy increased all five participants' latency to engaging in
      stereotypy; however, clinically significant omission durations were only achieved
      for one participant. Experiment 5 showed that differential reinforcement of
      alternative behavior in which participants earned access to the HP-LS stimulus
      contingent upon correct responses during discrete-trial training reduced targeted
      and nontargeted stereotypy and increased correct academic responding for all four
      participants. The potential utility of the FOCSA is discussed.

PMID- 29172683
TI  - New technique of percutaneous CT fluoroscopy-guided marking before video-assisted
      thoracoscopic surgery for small lung lesions: feasibility of using a 25-gauge
      needle without local anaesthesia.
AB  - OBJECTIVE: To retrospectively evaluate the feasibility of CT fluoroscopy-guided
      percutaneous marking using a 25-gauge needle and indigo carmine before video
      assisted thoracoscopic surgery (VATS) for small lung lesions. METHODS: 21
      patients, 14 males and 7 females, with a median age of 69 years (range, 40-79),
      underwent CT fluoroscopy-guided percutaneous VATS marking using a 25-gauge, 70-mm
      needle and 1.5-ml indigo carmine. The mean diameter of the lung lesions was 14 mm
      (range, 6-27). We evaluated the technical success rate, surgical success rate and
      complications related to this procedure by reviewing medical records and images.
      Technical success was defined as completion of this procedure. Surgical success
      was defined as resection of the target lesion with negative margins on
      pathological examination after VATS. Complications that required advanced levels
      of care were classified as major complications, and the remaining complications
      were considered minor. RESULTS: The technical success rate was 100%. In all
      cases, VATS was successfully performed as planned, and the target lesion was
      resected with negative margins on pathological examination after VATS. Thus, the
      surgical success rate was 100%. Mild pneumothorax was found in two cases, but
      further treatment was not required. The minor complication rate was 9.5% (2/21),
      and major complication rate was 0%. Only two patients (9.5%) complained of slight
      pain upon puncture, but local anaesthesia was not required. CONCLUSION:
      Percutaneous CT fluoroscopy-guided VATS marking using a 25-gauge needle without
      local anaesthesia appears feasible and safe. Advances in knowledge: This
      technique expands a possibility of the CT-guided marking.

PMID- 29172682
TI  - Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from
      Patients with Acute Myeloid Leukemia: A SWOG Report.
AB  - INTRODUCTION: Current prognostic models for acute myeloid leukemia (AML) are
      inconsistent at predicting clinical outcomes for individual patients. Variability
      in the quality of specimens utilized for biomarker discovery and validation may
      contribute to this prognostic inconsistency. METHODS: We evaluated the impact of
      sample heterogeneity on prognostic biomarkers and methods to mitigate any adverse
      effects of this heterogeneity in 240 cryopreserved bone marrow and peripheral
      blood specimens from AML patients enrolled on SWOG (Southwest Oncology Group)
      trials. RESULTS: Cryopreserved samples displayed a broad range in viability (37%
      with viabilities <=60%) and nonleukemic cell contamination (13% with lymphocyte
      percentages >20%). Specimen viability was impacted by transport time, AML
      immunophenotype, and, potentially, patients' age. The viability and cellular
      heterogeneity in unsorted samples significantly altered biomarker results.
      Enriching for viable AML blasts improved the RNA quality from specimens with poor
      viability and refined results for both DNA and RNA biomarkers. For example, FLT3
      ITD allelic ratio, which is currently utilized to risk-stratify AML patients, was
      on average 1.49-fold higher in the viable AML blasts than in the unsorted
      specimens. CONCLUSION: To our knowledge, this is the first study to provide
      evidence that using cryopreserved specimens can introduce uncontrollable
      variables that may impact biomarker results and enrichment for viable AML blasts
      may mitigate this impact.

PMID- 29172684
TI  - Faster and safer? FLASH ultra-high dose rate in radiotherapy.
AB  - Recent results from the Franco-Swiss team of Institute Curie and Centre
      Hospitalier Universitaire Vaudois demonstrate a remarkable sparing of normal
      tissue after irradiation at ultra-high dose rate (>40 Gy s-1). The "FLASH"
      radiotherapy maintains tumour control level, suggesting that ultra-high dose rate
      can substantially enhance the therapeutic window in radiotherapy. The results
      have been obtained so far only with 4-6 MeV electrons in lung and brain mouse
      model. Nevertheless, they have attracted a great attention for the potential
      clinical applications. Oxygen depletion had been discussed many years ago as a
      possible mechanism for reduction of the damage after exposure to ultra-high dose
      rate. However, the mechanism underlying the effect observed in the FLASH
      radiotherapy remains to be elucidated.

PMID- 29172685
TI  - Attempts to redefine conflicts of interest.
AB  - The traditional legal concept of conflict of interest is a practical tool to
      regulate conduct. In recent years several medical authors have defined conflicts
      of interest in ways that stray from its original legal meaning. The new
      definitions cause conceptual confusion and will result in policies that cannot be
      implemented effectively. We should not follow recent attempts to redefine
      conflicts of interest because doing so deviates from the legal concept and will
      lead to deregulation of financial conflicts and overregulation of so-called
      intellectual conflicts.

PMID- 29172686
TI  - Prenylated flavonoids and dihydrophenanthrenes from the leaves of Epimedium
      brevicornu and their cytotoxicity against HepG2 cells.
AB  - Phytochemical study on the leaves of Epimedium brevicornu finally led to the
      isolation of four prenylated flavonoids (1-4) and three dihydrophenanthrenes (5
      7), of which 1, 2, 5 and 7 were new compounds. The structures of these compounds
      were established mainly by spectroscopic techniques, including NMR spectroscopy
      and mass spectrometry. These isolates exhibited the cytotoxic activities against
      HepG2 cells with the IC50 values of 32.8-87.3 MUM.

PMID- 29172687
TI  - European cardiovascular nurses' and allied professionals' knowledge and practical
      skills regarding cardiopulmonary resuscitation.
AB  - PURPOSE: Cardiopulmonary resuscitation (CPR) remains a cornerstone in the
      treatment of cardiac arrest, and is directly linked to survival rates. Nurses are
      often first responders and need to be skilled in the performance of
      cardiopulmonary resuscitation. As cardiopulmonary resuscitation skills
      deteriorate rapidly, the purpose of this study was to investigate whether there
      was an association between participants' cardiopulmonary resuscitation training
      and their practical cardiopulmonary resuscitation test results. METHODS: This
      comparative study was conducted at the 2014 EuroHeartCare meeting in Stavanger (
      n=133) and the 2008 Spring Meeting on Cardiovascular Nursing in Malmo ( n=85).
      Participants performed cardiopulmonary resuscitation for three consecutive
      minutes CPR training manikins from Laerdal Medical(r). Data were collected with a
      questionnaire on demographics and participants' level of cardiopulmonary
      resuscitation training. RESULTS: Most participants were female (78%) nurses (91%)
      from Nordic countries (77%), whose main role was in nursing practice (63%), and
      71% had more than 11 years' experience ( n=218). Participants who conducted
      cardiopulmonary resuscitation training once a year or more ( n=154) performed
      better regarding ventilation volume than those who trained less (859 ml vs. 1111
      ml, p=0.002). Those who had cardiopulmonary resuscitation training offered at
      their workplace ( n=161) also performed better regarding ventilation volume (889
      ml vs. 1081 ml, p=0.003) and compression rate per minute (100 vs. 91, p=0.04)
      than those who had not. CONCLUSION: Our study indicates a positive association
      between participants' performance on the practical cardiopulmonary resuscitation
      test and the frequency of cardiopulmonary resuscitation training and whether
      cardiopulmonary resuscitation training was offered in the workplace. Large
      ventilation volumes were the most common error at both measuring points.

PMID- 29172688
TI  - Effect of nanoparticle treatment on expression of a key gene involved in
      thymoquinone biosynthetic pathway in Nigella sativa L.
AB  - Thymoquinone is the most important secondary metabolite in black Cumin, which has
      several pharmaceutical applications. In this study, effect of TiO2 and SiO2
      nanoparticles as new elicitors, on expression of Geranyl diphosphate synthase
      gene (GPPS gene), as a key gene involved in thymoquione biosynthesis pathway was
      investigated in two Iranian accessions. Plants were treatment in the early
      flowering stage and after 24 h of 50 and 100 mg/L of each nanoparticle,
      separately. After RNA extraction, GPPS gene expression was analysed by qRT-PCR
      method. The results showed that the TiO2 and SiO2 nanoparticles, generally
      stimulates the GPPS expression. The TiO2 nanoparticles were more effective than
      SiO2 for the induction of GPPS expression. Also, 100 mg/L treatment of
      nanoparticles raised gene expression more than 50 mg/L concentration. It can be
      concluded these nanoparticles can be used as robust elicitors to enhance the
      production of Thymoquinone in black cumin through up-regulation of related
      metabolic pathway genes.

PMID- 29172689
TI  - Stress Fracture of the Fifth Metatarsal in Foot Deformity Secondary to
      Neuromuscular Disease: Experiences of Deformity Correction Treatment-A Report of
      3 Cases and Review of the Literature.
AB  - : Fractures at the proximal metaphyso-diaphyseal junction of the fifth metatarsal
      are associated with high rates of delayed union. When these fractures are the
      result of repeated stress in patients with equinovarus hindfoot, which in turn is
      caused by neurological disorders, delayed union is the rule. Therefore, in
      neurological patients with stress fractures, optimal treatment would be to
      achieve a plantigrade foot enabling them to relieve the fifth metatarsal
      overload, which prevents the consolidation. We report 3 cases of fifth metatarsal
      stress fracture resulting from an equinovarus hindfoot deformity caused by a
      neuromuscular disease. Our surgical indication was to correct the foot deformity
      with no direct action on the fracture. Once a good alignment (plantigrade foot)
      was obtained, stress causing the fracture disappeared, and union was achieved
      with optimal biomechanical function in all 3 fractures. When stress fracture of
      the fifth metatarsal is caused by a secondary foot deformity, treating the
      deformity can lead to healing the fracture efficiently and should be considered
      prior to indicating surgical stabilization of the fracture itself. Primary
      treatment of the fracture with no correction of the deformity leads to
      therapeutic failure. LEVELS OF EVIDENCE: Therapeutic, Level IV.

PMID- 29172690
TI  - Role of MeCP2 in neurological disorders: current status and future perspectives.

PMID- 29172691
TI  - Two new sesquiterpenes derivatives from marine fungus Leptosphaerulina Chartarum
      sp. 3608.
AB  - Two new sesquiterpenes, leptoterpenes A (1) and B (2) were isolated from the
      fungus Leptosphaerulina Chartarum sp. 3608, derived from a crinoid. It was the
      first chemical study on this species. The structures of these compounds were
      elucidated by spectroscopic methods including NMR and MS spectrometry. The
      absolute configurations of the new compounds were determined on the basis of the
      single-crystal X-ray diffraction and electronic circular dichroism data analysis.
      All compounds were tested for their anti-inflammatory activity and the inhibitory
      effects on Tyrosyl DNA phosphodiesterase II (TDP2).

PMID- 29172692
TI  - Phenolic profiles of Serbian autochthonous variety 'Prokupac' and monovarietal
      international wines from the Central Serbia wine region.
AB  - Phenolic profiles of young monovarietal white and red wines from the Central
      Serbia were investigated. Quantification of phenolics was done using ultra-high
      performance liquid chromatography (UHPLC) coupled with a diode array detector and
      a triple-quadrupole mass spectrometer. Generally, red wines were characterised
      with higher phenolics content when compared to the white wines. This applies also
      for the total phenolics content (TPC) and radical scavenging activity (RSA)
      values. Among all the samples, the red wine from autochthonous Serbian variety
      'Prokupac' stood out with unique composition, showing the highest TPC, RSA and
      the highest concentration of the individual phenolics. Finally, based on a
      specific phenolic pattern, principal component analysis (PCA) indicated
      clustering of red and white wines, with the 'Prokupac' as a prominent outlier.

PMID- 29172693
TI  - Ephedrine as a lead compound for the development of new DPP-IV inhibitors.
AB  - AIM: Extracts from Ephedra species have been reported to be effective as
      antidiabetics. A previous in silico study predicted that ephedrine and five
      ephedrine derivatives could contribute to the described antidiabetic effect of
      Ephedra extracts by inhibiting dipeptidyl peptidase IV (DPP-IV). Finding
      selective DPP-IV inhibitors is a current therapeutic strategy for Type 2 diabetes
      mellitus management. Therefore, the main aim of this work is to experimentally
      determine whether these alkaloids are DPP-IV inhibitors. Materials & methods: The
      DPP-IV inhibition of Ephedra's alkaloids was determined via a competitive-binding
      assay. Then, computational analyses were used in order to find out the protein
      ligand interactions and to perform a lead optimization. RESULTS: Our results show
      that all six molecules are DPP-IV inhibitors, with IC50 ranging from 124 MUM for
      ephedrine to 28 mM for N-methylpseudoephedrine. CONCLUSION: Further computational
      analysis shows how Ephedra's alkaloids could be used as promising lead molecules
      for designing more potent and selective DPP-IV inhibitors.

PMID- 29172694
TI  - Epigenetic profiles in polyglutamine disorders.
AB  - The dominant polyglutamine (polyQ) disorders are a group of progressive and
      incurable neurodegenerative disorders, which are caused by unstable expanded CAG
      trinucleotide repeats in the coding regions of their respective causative genes.
      The most prevalent polyQ disorders worldwide are Huntington's disease and
      spinocerebellar ataxia type 3. Epigenetic mechanisms, such as DNA methylation,
      histone modifications and chromatin remodeling and noncoding RNA regulation,
      regulate gene expression or genome function. Epigenetic dysregulation has been
      suggested to play a pivotal role in the pathogenesis of polyQ disorders. Here, we
      summarize the current knowledge of epigenetic changes present in several
      representative polyQ disorders and discuss the potentiality of miRNAs as
      therapeutic targets for the clinic therapy of these disorders.

PMID- 29172696
TI  - Evaluation of Empowerment in Health Promotion Interventions: A Systematic Review.
AB  - Although empowerment is one of the core principles of the World Health
      Organization's approach to health promotion, there are no standards, best
      practice recommendations, or guidelines for evaluating empowerment within
      interventions. For the development of effective empowerment promoting
      interventions, adequate study designs, methods, and indicators for assessing
      empowerment are essential. In order to better understand which evaluation
      procedures have been used so far, and which advantages and disadvantages are
      connected to them, we systematically reviewed empowerment-based health promotion
      interventions. We included 26 studies, which use a broad variety of quantitative,
      qualitative, and mixed-methods designs and various data collection methods;
      qualitative and mixed-methods designs predominated. The quantitative measurement
      instruments are heterogeneous: Mainly self-designed or modified scales are
      applied. All studies consider indicators reflecting individual competencies and
      motivations, whereas indicators capturing the organizational and political
      components of empowerment are less common. Involving target group members in the
      development of evaluation procedures and combining different data sources are
      mentioned as specific steps to improve the quality of data collection. Given the
      flexible and context-dependent nature of empowerment approaches, the development
      of a "gold standard" for its evaluation seems unrealistic. However, the analyzed
      studies can be used to deduce recommendations that may help to conduct high
      quality evaluations of empowerment, for example, mixed-methods designs,
      participation of target groups, and reflective loops within the research team.

PMID- 29172697
TI  - What are dementia champions and why do we need them?

PMID- 29172695
TI  - Maternal alcohol consumption and offspring DNA methylation: findings from six
      general population-based birth cohorts.
AB  - AIM: Alcohol consumption during pregnancy is sometimes associated with adverse
      outcomes in offspring, potentially mediated by epigenetic modifications. We aimed
      to investigate genome-wide DNA methylation in cord blood of newborns exposed to
      alcohol in utero. MATERIALS & METHODS: We meta-analyzed information from six
      population-based birth cohorts within the Pregnancy and Childhood Epigenetics
      consortium. RESULTS: We found no strong evidence of association at either
      individual CpGs or across larger regions of the genome. CONCLUSION: Our findings
      suggest no association between maternal alcohol consumption and offspring cord
      blood DNA methylation. This is in stark contrast to the multiple strong
      associations previous studies have found for maternal smoking, which is similarly
      socially patterned. However, it is possible that a combination of a larger sample
      size, higher doses, different timings of exposure, exploration of a different
      tissue and a more global assessment of genomic DNA methylation might show
      evidence of association.

PMID- 29172698
TI  - Regulation of UGT1A expression by miR-298 in human livers from the Han Chinese
      population and in human cell lines.
AB  - AIM: This study aimed to investigate the role of miRNAs in UGT1A regulation.
      MATERIALS & METHODS: Based on bioinformatic prediction results, luciferase
      reporter assay and cell-transfection experiments were performed to study effects
      of miR-298 on UGT1A expression. Correlation study was conducted in human livers.
      RESULTS: miR-298 overexpression reduced mRNA level of UGT1A1 and UGT1A4 in HepG2
      and LS174T cells, and that of UGT1A3 and UGT1A9 in LS174T cells. miR-298
      repression increased mRNA level of UGT1A4 in HepG2 and LS174T cells, and that of
      UGT1A1 and UGT1A3 in LS174T cells. Inverse correlations between miR-298, as well
      as miR-491-3p, and UGT1A3 and 1A4 mRNA levels were observed in livers.
      CONCLUSION: The study demonstrates that miR-298 and miR-491-3p downregulates
      UGT1A expression.

PMID- 29172699
TI  - Antimalarial and cytotoxic activities of pregnene-type steroidal alkaloids from
      Holarrhena pubescens roots.
AB  - The phytochemical investigation of an alkaloidal extract of Holarrhena pubescens
      roots led to the isolation and identification of a new pregnene-type alkaloid,
      mokluangin D (1), together with nine known steroidal alkaloids (2-10). The
      structure of the new metabolite was determined on the basis of spectroscopic
      analyses including 1D- and 2D-NMR spectroscopy and mass spectrometry. Compounds 3
      and 4 showed potent antimalarial activity against Plasmodium falciparum K1 stain
      with IC50 values of 1.2 and 2.0 MUM, respectively, and showed weak cytotoxic
      activity against the NCI-H187 cell line with IC50 values of 27.7 and 30.6 MUM,
      respectively. The substituent groups at C-3 and the carbonyl group at C-18 are
      important for the activity against the P. falciparum K1 stain.

PMID- 29172700
TI  - A systematic review of acculturation, obesity and health behaviours among
      migrants to high-income countries.
AB  - Objective There is extensive evidence for weight gain among people migrating from
      low/middle-income to high-income countries, which may be due, in part, to
      acculturation factors. This review aimed to identify associations between
      acculturation and body weight among immigrants to high-income countries and
      identify if studies accounted for the role played by health behaviours. Methods A
      systematic literature search using keywords was performed with three databases
      (Medline, PsychINFO and EMBASE). The 35 studies were included that utilised
      quantitative methodology and presented empirical findings focused on
      acculturation and body weight among adult immigrants. Findings There was evidence
      presented across multiple studies for an association between acculturation
      (measured with standard measures or as duration of stay) and obesity. Most
      studies were cross sectional, which did not allow the exploration of drivers of
      change in health behaviours and weight gain. Conclusion This is the first review
      to examine associations between acculturation and body weight among migrants
      utilising both acculturation scales and proxy measures of acculturation and to
      examine the role of health behaviours. Evidence from this review suggests that
      health interventions should target first generation migrants to promote retention
      of their original healthy behaviours. Recent migrant groups report healthier
      behaviours than comparative host country populations, and therefore interventions
      should be promoted at the initial stages following migration to avoid uptake of
      unhealthy behaviours.

PMID- 29172701
TI  - The protection of unrepresented patients in emergency care research.
AB  - In emergency care research, it may be the case that neither informed consent nor
      surrogate consent is possible. In order to nonetheless allow for such research,
      codes and regulations of research ethics have increasingly incorporated
      provisions regarding this specific situation. The protection that those
      provisions offer need to be better understood. This article addresses in what
      ways they protect individuals, and especially the extent to which the suggested
      protection compensates for the loss of surrogate consent. The Declaration of
      Helsinki, the Additional Protocol to the Convention on Human Rights and
      Biomedicine, and the EU Clinical Trials Regulation serve as the main
      illustrations.

PMID- 29172702
TI  - Using Panel Vendors for Recruitment Into a Web-Based Family Prevention Program:
      Methodological Considerations.
AB  - Use of online panel vendors in research has grown over the past decade. Panel
      vendors are organizations that recruit participants into a panel to take part in
      web-based surveys and match panelists to a target audience for data collection.
      We used two panel vendors to recruit families ( N = 411) with a 16- to 17-year
      old teen to participate in a randomized control trial (RCT) of an online family
      based program to prevent underage drinking and risky sexual behaviors. Our
      article addresses the following research questions: (1) How well do panel vendors
      provide a sample of families who meet our inclusion criteria to participate in a
      RCT? (2) How well do panel vendors provide a sample of families who reflect the
      characteristics of the general population? and (3) Does the choice of vendor
      influence the characteristics of families that we engage in research? Despite the
      screening techniques used by the panel vendors to identify families who met our
      inclusion criteria, 23.8% were found ineligible when research staff verified
      their eligibility by direct telephone contact. Compared to the general U.S.
      population, our sample had more Whites and more families with higher education
      levels. Finally, across the two panel vendors, there were no significant
      differences in the characteristics of families, except for mean age. The online
      environment provides opportunities for new methods to recruit participants in
      research studies. However, innovative recruitment methods need careful study to
      ensure the quality of their samples.

PMID- 29172703
TI  - Quantitative EEG Parameters for Prediction of Outcome in Severe Traumatic Brain
      Injury: Development Study.
AB  - Monitoring of quantitative EEG (QEEG) parameters in the intensive care unit (ICU)
      can aid in the treatment of traumatic brain injury (TBI) patients by
      complementing visual EEG review done by an expert. We performed an explorative
      study investigating the prognostic value of 59 QEEG parameters in predicting the
      outcome of patients with severe TBI. Continuous EEG recordings were done on 28
      patients with severe TBI in the ICU of Turku University Hospital. We computed a
      set of QEEG parameters for each patient, and correlated these to patient outcome,
      measured by dichotomized Glasgow Outcome Scale (GOS) at a follow-up visit between
      6 and 12 months, using area under receiver operating characteristic curve (AUC)
      as a nonlinear correlation measure. For 17 of the 59 QEEG parameters (28.8%), the
      AUC differed significantly from 0.5, most of these parameters measured EEG power
      or variability. The best QEEG parameters for outcome prediction were alpha power
      (AUC = 0.87, P < .01) and variability of the relative fast theta power (AUC =
      0.84, P < .01). The results of this study indicate that QEEG parameters provide
      useful information for predicting outcome in severe TBI. Novel QEEG parameters
      with potential in outcome prediction were found, the prognostic value of these
      parameters should be confirmed in later studies. The results also provide further
      evidence of the usefulness of parameters studied in preexisting studies.

PMID- 29172705
TI  - Expression of iron-related proteins in feline and canine mammary gland reveals
      unexpected accumulation of iron.
AB  - Dysregulation of cellular iron homeostasis in human breast cancer is reflected by
      the altered expression of regulatory proteins. The expressions of iron-related
      proteins in the mammary glands of cats and dogs have not been assessed. We
      evaluated the expressions of ferritin, ferroportin, hepcidin and transferrin
      receptor 1 in benign and malignant mammary gland lesions in cats and dogs. Iron
      deposition was detected using Perls' Prussian blue staining. We found no major
      differences in the expression of iron-related proteins between benign and
      malignant mammary gland lesions in either cats or dogs; however, these species
      exhibited accumulation of iron in benign lesions. Our findings provide an
      explanation for the absence of higher iron requirements by tumor cells in these
      animals. Further investigation of local iron homeostasis in cats and dogs and
      differences in their physiology compared to human breast cancer is required.

PMID- 29172706
TI  - Methylation changes and pathways affected in preterm birth: a role for SLC6A3 in
      neurodevelopment.
AB  - AIM: To analyze whether preterm newborns show differences in methylation patterns
      in comparison to full-term newborns in white blood cells. PATIENTS & METHODS:
      Anthropometrical, biochemical features and methylation levels of preterm newborns
      (n = 24) and full-term newborns (n = 22) recruited in La Paz University Hospital
      (Spain) were assessed at 12 months of gestational age, whereas Bayley Scale of
      Infant Development was evaluated at 24/36 months. RESULTS: From all the
      statistically significant CpGs, methylation levels of cg00997378 (SLC6A3 gene)
      showed the highest differences (p < 0.0001), being associated with prematurity
      risk factors. CONCLUSION: SLC6A3 methylation, previously related to attention
      deficit/hyperactivity disorder, neuronal function and behavior, might be a
      potential epigenetic biomarker with value in the early diagnosis and management
      of neurodevelopmental diseases in newborns.

PMID- 29172707
TI  - Growth kinetics and diosgenin estimation from callus cultures of Costus speciosus
      (Koen. ex. Retz.).
AB  - The present investigation reports the growth kinetics and diosgenin accumulation
      in callus cultures of Costus speciosus. Effect of explants, media and plant
      growth regulators was evaluated with respect to callus induction and growth. Out
      of the two explants viz pseudostem and seed, pseudostem showed maximum callus
      induction frequency of 90% on MS medium. The fresh weight of callus was maximum
      (9-folds) on 28th day on 1.0 mg/L picloram containing medium. The callus obtained
      was white compact hard (WCH). For growth kinetics study pseudostem derived callus
      was transferred on different media supplemented with 1.0 mg/L picloram. All
      phases of growth were seen in callus inoculated on all the three media except the
      absence of stationary phase on MS and SH media. MS medium proved to be the best
      for maximum biomass accumulation (9-fold) on 28th day of culture and callus in
      post-exponential phase showed maximum diosgenin accumulation (33 ppm).

PMID- 29172708
TI  - A Comparative Study on the Role of Xpert MTB/RIF in Testing Different Types of
      Spinal Tuberculosis Tissue Specimens.
AB  - AIMS: The aim of the present study was to compare the efficacy of the commercial
      Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) test for evaluating different
      types of spinal tuberculosis (TB) tissue specimens. METHODS: Pus, granulation
      tissue, and caseous necrotic tissue specimens from 223 patients who were
      diagnosed with spinal TB and who underwent curettage were collected for bacterial
      culture and the Xpert MTB/RIF assay to calculate the positive rate. Bacterial
      culture and phenotypic drug sensitivity testing (pDST) were adopted as the gold
      standards to calculate the sensitivity and specificity of the Xpert bacterial
      detection and drug resistance (DR) test. RESULTS: The positive rate (68.61% +/-
      7.35%) from the Xpert MTB/RIF assays of spinal TB patients' tissue specimens was
      higher compared with bacterial culture (44.39% +/- 6.51%, Z = 5.1642, p < 0.01),
      and the positive rates from Xpert MTB/RIF assays on the three types of specimens
      were all higher than those of bacterial culture, with statistically significant
      results for pus and granulation tissue specimens. The positive rates for pus
      using the two bacteriological tests were higher than those for granulation tissue
      but were not statistically significant. However, the positive rates obtained from
      granulation tissue were statistically significantly higher than those obtained
      from caseous necrotic tissue. With bacterial culture and pDST as the gold
      standards, the sensitivity of Xpert MTB/RIF assays for MTB was 96.97%, while the
      sensitivity and specificity of the DR test also remained relatively high.
      CONCLUSION: For efficient and accurate diagnosis of spinal TB and DR and timely
      provision of effective treatment, multiple specimens, especially the pus of
      spinal TB patients, should be collected for Xpert MTB/RIF assays.

PMID- 29172709
TI  - Curcumin Suppresses In Vitro Proliferation and Invasion of Human Prostate Cancer
      Stem Cells by Modulating DLK1-DIO3 Imprinted Gene Cluster MicroRNAs.
AB  - AIMS: Curcumin can suppress human prostate cancer (HuPCa) cell proliferation and
      invasion. However, it is not known whether curcumin can inhibit HuPCa stem cell
      (HuPCaSC) proliferation and invasion. MATERIALS AND METHODS: We used methyl
      thiazolyl tetrazolium and Transwell assays to examine the proliferation and
      invasion of the HuPCaSC lines DU145 and 22Rv1 following curcumin or dimethyl
      sulfoxide (control) treatment. The microRNA (miRNA) expression levels in the DLK1
      DIO3 imprinted genomic region in the cells and in tumor tissues from patients
      with PCa were examined using microarray and quantitative PCR. RESULTS: The median
      inhibitory concentration of curcumin for HuPCa cells significantly inhibited
      HuPCaSC proliferation and invasion in vitro. The miR-770-5p and miR-1247
      expression levels in the DLK1-DIO3 imprinted gene cluster were significantly
      different between the curcumin-treated and control HuPCaSCs. Overexpression of
      these positive miRNAs significantly increased the inhibition rates of miR-770-5p-
      and miR-1247-transfected HuPCaSCs compared to the control miR-Mut-transfected
      HuPCaSCs. Lastly, low-tumor grade PCa tissues had higher miR-770-5p and miR-1247
      expression levels than high-grade tumor tissues. CONCLUSIONS: Curcumin can
      suppress HuPCaSC proliferation and invasion in vitro by modulating specific
      miRNAs in the DLK1-DIO3 imprinted gene cluster.

PMID- 29172710
TI  - Low rates of post-craniotomy surgical site infections in a developing country:
      surgical technique and results.
AB  - INTRODUCTION: Although neurosurgical surgical site infections (SSI) exert a
      devastating price on the postoperative course of patients in the developing
      countries, literature is sparse on the subject from these regions. METHODS: This
      study is an audit of post-craniotomy SSI in a sub-Sahara African academic
      neurosurgical practice. It is a retrospective descriptive analysis of
      neurosurgical SSI in a 7-year consecutive cohort of patients who survived more
      than 5 days following major cranial surgery. Our general neurosurgical operative
      goal is to keep the incidence of SSI as close to the global range as possible by,
      amongst other measures, enforcing strict compliance with appropriate operative
      room practice. RESULTS: There were 211 craniotomies/craniectomies; 194 primary
      and 17 redo procedures. Male patients constituted 65%. The mean age was 32.2
      (Standard Deviation +/- 17.2) years. The procedures were emergencies in 42.7% and
      urgent or elective in the rest. They were surgery for trauma in 46.9% and for
      tumour resections in 44.1%. The median duration of surgery was 3 hours (range 1
      8.5 hours). Mortality was 4.3%. Functional outcome was assessed using a
      dichotomized Glasgow Outcome Scale and was good in 90.5%. Surgical site
      infections, mainly by Gram negative coliforms, occurred in 9 cases, 4.3%, leading
      to worse in-hospital outcome of 56% (p < .001) in those affected. Patients with a
      poorer pre-operative Karnofsky performance status had a higher infection rate
      (7.5%), than those with better clinical performance index, (2.3%). This
      difference was not significant (p = .09, unadjusted OR 3.46, 95% Confidence
      Interval 0.84-14.24). CONCLUSION: Post-craniotomy SSI rates comparable to those
      in more advanced practice areas is achievable in developing countries.

PMID- 29172711
TI  - Decision-making in children in the Hungry Donkey Test: A behavioral analysis.
AB  - This study analyzed choice behavior in the Hungry Donkey Task, with a focus on
      learning trajectories and the stability of preference, in 100 children of
      different ages (8-9, 10-11, 12-13, 14-15, and 16-17 years old). The results
      indicated that (a) learning occurred as the task progressed, (b) early
      adolescents performed poorly during the task, and (c) most of the participants
      did not reach the stability criterion during the task. The present study suggests
      that decision-making in children and adolescents varies with age, and that the
      inclusion of an operant-based approach (e.g., the use of stability criterion) may
      improve methods for evaluating decision-making in children.

PMID- 29172712
TI  - Decompressive craniectomy in aneurysmal subarachnoid haemorrhage for hematoma or
      oedema versus secondary infarction.
AB  - PURPOSE: Decompressive craniectomy (DC) has been proposed as lifesaving treatment
      in aneurysmal subarachnoid haemorrhage (aSAH) patients with elevated intracranial
      pressure (ICP). However, data is sparse and controversy exists whether the
      underlying cause of elevated ICP influences neurological outcome. The purpose of
      this study is to clarify the role of the underlying cause of elevated ICP on
      outcome after DC. MATERIALS AND METHODS: We retrospectively studied the one-year
      neurological outcome in a single-centre cohort to identify predictors of
      favourable (Glasgow Outcome Scale (GOS) 4-5) and unfavourable (GOS 1-3) outcome.
      Additionally, available individual patient data in the literature was reviewed
      with a special emphasis on the underlying reason for DC. RESULTS: From 2006-2015,
      53 consecutive aSAH patients underwent DC. Nine (17%) achieved favourable, 44
      (83%) unfavourable outcome (31 patients died). One fourth of the patients
      undergoing DC for hematoma or (hematoma-related) oedema survived favourably
      (increasing to 46% for patients aged <51 years), versus none of the patients
      undergoing DC for secondary infarction. Analysis of individual data of 105
      literature patients showed a similar trend, although overall outcome was much
      better: half of the patients undergoing DC for hematoma/oedema regained
      independence, versus less than one-fourth of patients undergoing DC for secondary
      infarction. CONCLUSIONS: DC in aSAH patients is associated with high rates of
      unfavourable outcome and mortality, but hematoma or oedema as underlying reason
      for DC is associated with better outcome profiles compared to secondary
      infarction. Future observational cohort studies are needed to further explore the
      different outcome profiles among subpopulations of aSAH patients requiring DC.

PMID- 29172714
TI  - Heroes or Health Victims?: Exploring How the Elite Media Frames Veterans on
      Veterans Day.
AB  - We examine the frames the elite news media uses to portray veterans on and
      surrounding Veterans Day 2012, 2013, 2014, and 2015. We use mental health illness
      and media framing literature to explore how, why, and to what extent Veterans Day
      news coverage uses different media frames across the four consecutive years. We
      compiled a Media Coverage Corpora for each year, which contains the quotes and
      paraphrased remarks used in all veterans news stories for that year. In our
      primary study, we applied the meaning extraction method (MEM) to extract emergent
      media frames for Veterans Day 2014 and compiled a word frequency list, which
      captures the words most commonly used within the corpora. In post hoc analyses,
      we collected news stories and compiled word frequency lists for Veterans Day
      2012, 2013, and 2015. Our findings reveal dissenting frames across 2012, 2013,
      and 2014 Veterans Day media coverage. Word frequency results suggest the 2012 and
      2013 media frames largely celebrate Veterans as heroes, but the 2014 coverage
      depicts veterans as victimized by their wartime experiences. Furthermore, our
      results demonstrate how the prevailing 2015 media frames could be a reaction to
      2014 frames that portrayed veterans as health victims. We consider the
      ramifications of this binary portrayal of veterans as either health victims or
      heroes and discuss the implications of these dueling frames for veterans' access
      to healthcare resources.

PMID- 29172713
TI  - Activation of the molecular and functional effects of Nrf2 against chronic iron
      oxide nanorod overload-induced cardiotoxicity.
AB  - Reactive oxygen species have a significant role in the pathogenesis of iron oxide
      nanorod (IONR) overload-induced organ toxicity in some organs such as the lungs.
      Green tea induces upregulation of phase II antioxidant enzymes that are
      transcriptionally organized by the nuclear factor (erythroid-derived 2)-like 2
      (Nrf2) that when activated antagonize the oxidative stress induced by IONR
      overload that causes cardiotoxicity. The aim of the present study was to
      determine whether treatment of cardiotoxicity with iron chelators (deferiprone
      (DFP) or deferoxamine (DFO)) alone or in combination with phytochemical
      activation of Nrf2 (green tea) can protect cardiomyocytes from IONR overload
      induced cardiotoxicity. One hundred five rats were distributed into seven groups:
      two control groups (non-IONR-overloaded and IONR-overloaded) and five IONR
      overloaded groups such as a green tea group, DFP group, DFP combined with green
      tea group, DFO group, and DFO combined with green tea. Blood samples and cardiac
      tissues were obtained for estimation of total iron-binding capacity, ratio of
      myocardial 8-hydroxy-2'-deoxyguanosine/myocardial 2-deoxyguanosine,
      thiobarbituric acid reactive substances, glutathione (GSH) contents, and
      histopathological examination. The results showed mild histopathological changes
      in the heart and a significant decrease in all biochemical parameters, except for
      myocardial GSH, in the DFP group. The addition of green tea improved the
      biochemical and histopathological results compared with chelators alone.

PMID- 29172715
TI  - The rationale and design of reduction of uncontrolled hypertension by Remote
      Monitoring and Telemedicine (REMOTE) study.
AB  - PURPOSE: Although self-measurement of home blood pressure (HBP) is common in
      Japan and HBP telemonitoring via the Internet is possible, whether telemonitoring
      improves HBP control better than conventional practice remains unclear.
      Furthermore, hypertension care with online communication using telemonitored HBP
      is feasible, whereas the efficacy and safety of such telemedicine have not been
      established. We aim to compare traditional care, care with office visits using
      HBP telemonitoring, and antihypertensive telemedicine based on HBP
      telemonitoring. METHODS AND DESIGN: In total, 444 patients with uncontrolled
      hypertension will be recruited and randomly assigned to three groups: (1)
      control: usual care with office visits and HBP self-report, (2) telemonitoring:
      weekly assessment of transmitted HBP by physicians and treatment adjustment upon
      office visits, or (3) telemedicine: online communication instead of office visits
      to adjust medication using telemonitored HBP. Primary outcome is the time to
      control of HBP, and secondary outcomes include achieved HBP levels, adherence,
      treatment intensity, adverse events, patient satisfaction and cost-effectiveness.
      DISCUSSION: Hypertension care with telemonitoring and telemedicine are expected
      to require shorter time to achieve HBP control compared to usual care. Combining
      HBP telemonitoring with telemedicine may lower the hurdles for starting and
      persisting to hypertension treatment and eventually reduce cardiovascular events.

PMID- 29172716
TI  - Aircraft Noise Exposure and Subjective Sleep Quality: The Results of the DEBATS
      Study in France.
AB  - BACKGROUND: Exposure to aircraft noise has been shown to have adverse effects on
      health, particularly on sleep. Exposure to nighttime aircraft noise clearly
      affects sleep architecture, as well as subjective sleep quality. OBJECTIVES: This
      study aimed to investigate the relationship between aircraft noise exposure and
      subjective sleep quality in the population living near airports in France.
      METHODS: A total of 1,244 individuals older than 18 and living near three French
      airports (Paris-Charles de Gaulle, Lyon-Saint-Exupery, and Toulouse-Blagnac) were
      randomly selected to participate in the study. Information on sleep as well as
      health, socioeconomic, and lifestyle factors was collected by means of a face-to
      face questionnaire performed at their place of residence by an interviewer. For
      each participant, aircraft noise exposure was estimated at home using noise maps.
      Logistic regression models were used with adjustment for potential confounders.
      RESULTS: Aircraft noise exposure was significantly associated with a short total
      sleep time (TST; <= 6 h) and with the feeling of tiredness while awakening in the
      morning. An increase of 10 dB(A) in aircraft noise level at night was associated
      with an OR of 1.63 (95% CI: 1.15-2.32) for a short TST and an OR of 1.23 (95% CI:
      1.00-1.54) for the feeling of tiredness while awakening in the morning.
      CONCLUSIONS: These findings contribute to the overall evidence suggesting that
      aircraft noise exposure at nighttime may decrease the subjective amount and
      quality of sleep.

PMID- 29172717
TI  - Comparative effectiveness of the biosimilar CT-P13.
AB  - The first biosimilar infliximab, CT-P13 (infliximab-dyyb) has been used for the
      treatment of inflammatory diseases for 4 years. CT-P13 has highly similar
      efficacy and safety profiles with a lower price than the originator infliximab
      and has been approved in 81 countries. Despite approval for clinical use, some
      knowledge gaps still limit the widespread and pertinent use of biosimilar CT-P13.
      One of the most important factors for proper utilization of CT-P13 for the
      treatment of immune-mediated inflammatory diseases is confidence in CT-P13, which
      could be enhanced by scientific evidence supporting the biosimilarity of CT-P13.
      Overall, five randomized controlled studies have been performed. For the other
      extrapolated indications, many observational induction and switching studies also
      support the utility of CT-P13 in the treatment of inflammatory diseases. Here, we
      review profiles of CT-P13 including physicochemical properties, clinical efficacy
      and safety data in all indications and current status.

PMID- 29172718
TI  - Lack of effects of myo-inositol on metabolism of primary rat adipocytes.
AB  - Myo-inositol is a ubiquitous cyclitol, has an important regulatory role, and its
      intracellular depletion is associated with pathological changes. Effects of myo
      inositol on adipose tissue are poorly elucidated. In this report, short-term
      influence of 20, 100, and 500 uM myo-inositol on metabolism of the isolated rat
      adipocytes was studied. Cells were incubated for 90 min with glucose and insulin
      with or without myo-inositol and glucose conversion to lipids and lactate release
      were measured. Moreover, effects of myo-inositol on lipolysis and on the
      antilipolytic action of insulin were also studied. It was demonstrated that
      lipogenesis and lactate release were unchanged by myo-inositol. Moreover,
      lipolytic response to epinephrine and dibutyryl-cAMP was also unchanged. Myo
      inositol was also found to be without influence on the antilipolytic action of
      insulin. Results of this study show that metabolism of the isolated rat
      adipocytes is not affected by short-term exposure of these cells to myo-inositol.

PMID- 29172719
TI  - T-cell receptor-mediated characteristic signaling pathway of peripheral blood T
      cells in dermatomyositis and polymyositis.
AB  - The characteristics of T cell expression in peripheral blood have been previously
      described in dermatomyositis (DM) and polymyositis (PM); however, their
      intracellular signaling profiles remain unknown. The purpose of this study was to
      investigate the T-cell receptor (TCR)-mediated intracellular signaling in
      peripheral blood T cells in DM and PM. Peripheral blood T cells from 86 patients
      with DM (n = 57) and PM (n = 29) were used for experimental investigations. T
      cell subtypes and TCR-induced phosphorylated zeta-chain-associated protein kinase
      70 (pZAP70) were analyzed by flow cytometry. Signal transducer and activator of
      transcription (STAT) and some inhibitory factors in T cells with TCR stimulation
      were also investigated by quantitative real-time polymerase chain reaction. T
      cell counts were significantly lower in DM than in PM. In addition, STAT,
      forkhead box transcription factor (FoxP3), and pZAP70 expression in CD4+ T cells
      was suppressed in DM, whereas STAT and pZAP70 expression in CD8+ T cells was
      induced in PM. Especially in DM, a positive correlation between CD4+ T cell
      counts and STAT expression was detected. In addition, low CD4+ T cell counts as
      well as reduced STAT expression were prominent in patients with interstitial lung
      disease. STAT and pZAP70 expression significantly improved after clinical
      remission in both DM and PM, although expression of FoxP3 remained suppressed.
      Besides, upregulation of suppressor of cytokine signaling-3 (SOCS3) and
      downregulation of interleukin 6 signal transducer (IL6ST) in CD4+ T cells were
      observed in both DM and PM; however, no significant improvements were detected
      after clinical remission. The results of the present study suggested that TCR
      mediated signaling may be a key pathway to determine the different
      characteristics of peripheral blood T cells between DM and PM. In addition,
      upregulation of SOCS3 and downregulation of IL6ST and FoxP3 in CD4+ T cells may
      cause an imbalance in intracellular signaling, especially in DM, suggesting that
      further studies are required to identify how the impaired signaling contributes
      to the development of the disease.

PMID- 29172720
TI  - Preliminary study on current perceptions and usage of training equipment by horse
      enthusiasts in Canada.
AB  - Training practices may impose restrictions on the equine behavioral repertoire
      through the use of training equipment. Presently, the prevalence of the use of
      training equipment in Canada is unknown. Through an online survey for horse
      enthusiasts (n = 654), this study evaluated the prevalence and predominant uses
      of whips, spurs, and head-control equipment by enthusiasts with direct contact
      with horses compared to perceptions held by enthusiasts with no direct horse
      contact using chi-squared analyses. Respondents primarily reported using whips
      and spurs to augment rider or trainer cues and reported using head-control
      equipment mainly for lunging purposes. The perceived frequency of spurs and head
      control equipment use during riding or training by nonactive horse enthusiasts
      was significantly greater than reported usage by riders and trainers (p < .05).
      The results potentially indicate a lack of understanding and miscommunication of
      training equipment use by riders and trainers. The frequent reporting of training
      equipment for the purpose of augmenting rider cues may imply misinterpretation of
      the correct application of learning theory. These preliminary results warrant
      further investigation of equipment use within the horse industry.

PMID- 29172721
TI  - Anogenital distance and variability in semen parameters.
AB  - : The purpose of this study was to analyze whether the anogenital distance (AGD)
      was associated with variability in semen parameters. Semen parameters analyzed
      following the WHO guidelines and sperm DNA fragmentation were evaluated in 160
      semen samples obtained over a period of a year from 16 healthy male volunteers.
      Two types of AGD measurements from the anus to the rear base of the scrotum
      (AGDAS) and to the cephalic insertion of the penis (AGDAP) were taken in each
      individual. The association between AGDs and semen parameters were studied using
      three statistical tools: a) general coefficient of variation (CV) and intra
      individual coefficient of variation (CVi), b) general linear models for repeated
      measures, and c) mixed model fixed effects panel data. Men with shortened AGDAP
      have significantly greater intra-individual variability in sperm concentration,
      total sperm count, and normal sperm morphology. Conversely, greater total sperm
      motility was observed in men with long AGDAS. Shortened AGDAS was associated with
      less intra-individual variability of total sperm motility (progressive and non
      progressive). AGD measurements were associated with the variability in semen
      parameters. AGD may be useful to determine intra-individual variability in semen
      parameters. ABBREVIATIONS: AGD: anogenital distance; AGDAP: anogenital distance
      from the anus to the cephalic insertion of the penis; AGDAS: anogenital distance
      from the anus to the rear base of the scrotum; AIC: Akaike information criteria;
      BMI: body mass index; CV: general coefficient of variation; CVi: intra-individual
      coefficient of variation; GLM: generalized linear model; PR+NP: total sperm
      motility.

PMID- 29172722
TI  - Effect of switch trimming on udder and teat hygiene of dairy cows.
AB  - The study objective was to determine the effects of trimming the switch of dairy
      cows on teat-end bacterial counts and udder hygiene scores. Cows (n = 102) were
      blocked by days in milk, milk production, and parity and then assigned to (a)
      treatment (trimming of their tail switch using a commercially available trimmer),
      or (b) control (unaltered tails). Udder hygiene was recorded for cows on Days 0
      (initiation of treatment), 32, and 64. A subset of cows (n = 21) was used to
      assess Streptococci and coliform bacterial populations on teat ends. Samples were
      collected by swabbing the left front teat end before milking on Days 0, 32, and
      64 and were cultured within 24 hr of sampling. The GLIMMIX and PROC Frequency
      (SAS Version 9.3) were used to analyze data. There were no treatment effects of
      switch trimming on hygiene scores or bacterial counts. These findings suggest
      that udder hygiene may not be driven by tail status. Environmental and management
      factors, such as cleanliness, stall bedding, and stall design, may be more
      important contributing factors in maintaining udder health.

PMID- 29172723
TI  - Subjective Sleep Related to Post Traumatic Stress Disorder Symptoms among Trauma
      Exposed Men and Women.
AB  - OBJECTIVE/BACKGROUND: Sleep difficulty is both a common symptom of posttraumatic
      stress disorder (PTSD) and a risk factor for the development and maintenance of
      PTSD symptomatology. Gender differences in sleep following trauma exposure have
      been posited to contribute to the increased risk for the development of PTSD
      among women, but the persistence and long-term contributions of these potential
      differences to the maintenance and severity of PTSD symptoms is unclear.
      PARTICIPANTS: Men and women reporting a history of trauma exposure (n = 112, 63%
      female) participated in this study. METHODS: Subjective sleep complaints and PTSD
      symptom severity were assessed using well-validated measures (Pittsburgh Sleep
      Quality Index, PTSD Symptom Checklist). Multivariable regression models (full
      sample and gender-stratified) were used to predict PTSD symptom severity from
      global, subscale, and individual item sleep parameters, adjusted for gender, age,
      race/ethnicity, education, and body mass index. RESULTS: In the full sample,
      traditional measures of sleep quality and sleep disturbance were associated with
      PTSD symptom severity. Difficulty falling asleep, poor sleep quality, and sleep
      disturbance from a variety of sources were related to higher PTSD symptom
      severity in men, while self-reported sleep disturbance related to nightmares and
      emotional regulation were associated with PTSD symptom severity among women.
      CONCLUSIONS: These findings add to the limited literature on gender-specific risk
      factors related to sleep and PTSD, and may inform intervention development and
      implementation related to PTSD severity among vulnerable adults.

PMID- 29172724
TI  - Distribution and Diversity of Ocular Microbial Communities in Diabetic Patients
      Compared with Healthy Subjects.
AB  - PURPOSE: The aim of this study was to identify differences in the major (core vs.
      variable) microbial genera of human subjects with and without diabetes. METHODS:
      Bacterial 16S rRNA genes obtained from conjunctival swabs of 19 healthy subjects
      and 30 diabetic patients were sequenced using the Illumina MiSeq platform, and
      the sequencing data were analyzed using QIIME 1.9.1. To elucidate the microbial
      diversity in the ocular surface (OS), test programs from various bioinformatics
      domains were used. RESULTS: Diversity index and rarefaction analysis showed that
      the microbial community of the diabetic patients was more diverse than that of
      the healthy subjects. Proteobacteria, Firmicutes, Actinobacteria, Cyanobacteria
      and Bacteroidetes were the dominant taxa present in the OS, and there was a
      significant difference in the relative abundance of the bacterial phyla between
      the diabetic patients and control subjects. Proteobacteria were more abundant in
      the diabetic group, whereas Firmicutes was more abundant in the control group.
      Analysis of bacterial taxa at the genus level showed that the core microbiome of
      diabetic patients comprised Acinetobacter, Burkholderia, Sphingomonas, and
      Ralstonia, whereas that of the controls comprised Bradyrhizobiaceae,
      Staphylococcus, Corynebacterium, Pseudomonas, Novosphingobium, Neisseriaceae, and
      Acinetobacter. CONCLUSIONS: There was a significant difference in the microbial
      community composition between diabetic patients and healthy subjects. A high
      abundance of Acinetobacter in the OS of diabetic patients may arise from the
      unique characteristics of the OS compared with those of other organ surfaces.

PMID- 29172725
TI  - Objective cognitive impairment and subjective cognitive problems in veterans
      initiating psychotherapy for posttraumatic stress disorder: An exploratory study.
AB  - The prevalence of cognitive impairment in Veterans initiating an evidence-based
      psychotherapy (EBP) for posttraumatic stress disorder (PTSD) is not yet
      established and has implications for service delivery. Our objectives were to (1)
      describe the type, severity, and prevalence of objective cognitive impairment and
      subjective cognitive problems experienced by Veterans at the time they began an
      EBP for PTSD and (2) determine whether assessments of objective cognitive
      impairment and subjective cognitive problems agree. We conducted objective and
      subjective (self-report) cognitive assessments in a sample of 38 Veterans
      initiating EBP for PTSD at one Veterans Affairs Medical Center. Thirty Veterans
      produced valid assessments. Almost half (14/30) of the participants demonstrated
      objective impairment in one or more cognitive domains, primarily in the areas of
      learning, memory, and processing speed. Almost all (29/30) participants endorsed
      moderate or greater cognitive problems on at least one self-report measure. After
      adjustment for multiple comparisons, there were no significant correlations
      between objective and subjective assessments. Objective cognitive impairment and
      subjective cognitive problems are common in Veterans beginning an EBP for PTSD.
      Longitudinal research on a larger sample is warranted to better understand
      relationships among subjective cognitive problems, objective cognitive
      impairment, and PTSD treatment participation and outcomes.

PMID- 29172726
TI  - Association between serum osteocalcin level and blood pressure in a Chinese
      population.
AB  - PURPOSE: This observational study investigated the association between serum
      osteocalcin level and blood pressure in a Chinese population. MATERIALS AND
      METHODS: A total of 2241 subjects (909 men and 1,332 women; age, 24-78 years)
      from Shanghai communities were recruited. Subjects were divided into non
      hypertensive and hypertensive groups according to diagnosis of hypertension based
      on the 1999 World Health Organization-International Society of Hypertension
      Guidelines. Serum osteocalcin levels were measured using an
      electrochemiluminescence immunoassay. RESULTS: Men in the hypertensive group
      showed lower serum osteocalcin level compared with those in the non-hypertensive
      group, [16.37 (13.34-20.11) ng/mL versus 17.01 (14.23-20.79) ng/mL, p = .039]. No
      difference in serum osteocalcin level was found between the two groups of women
      (p = .675). An inverse association was observed between serum osteocalcin level
      and systolic blood pressure (SBP) in men (p = .004), but serum osteocalcin level
      was not associated with diastolic blood pressure (DBP) in men (p = .472). No
      associations were detected between serum osteocalcin level and SBP or DBP in
      women (SBP: p = .108; DBP: p = .575). A multiple stepwise regression analysis
      showed an inverse association between serum osteocalcin level and SBP in men
      after adjusting for age, smoking status, family history of hypertension, and
      lipid and C-reactive protein levels (standardized beta = -0.074, p = .023), but
      the association disappeared after adjustment for body mass index, waist
      circumference, blood glucose, and homeostasis model assessment of insulin
      resistance (p = .327). CONCLUSIONS: Serum osteocalcin level was not independently
      associated with blood pressure in a Chinese population.

PMID- 29172727
TI  - Objective Versus Self-Reported Sleep Quality at High Altitude.
AB  - : Anderson, Paul J., Christina M. Wood-Wentz, Kent R. Bailey, and Bruce D.
      Johnson. Objective versus self-reported sleep quality at high altitude. High Alt
      Med Biol. 16:000-000, 2017. BACKGROUND: Previous studies have found little
      relationship between polysomnography and a diagnosis of acute mountain sickness
      (AMS) using the Lake Louise Symptom Questionnaire (LLSQ). The correlation between
      sleep question responses on the LLSQ and polysomnography results has not been
      explored. We compared LLSQ sleep responses and polysomnography data from our
      previous study of workers rapidly transported to the South Pole. METHODS: Sixty
      three subjects completed a 3-hour flight from sea level to the South Pole (3200
      m, 9800 ft). Participants completed limited overnight polysomnography on their
      first night and completed LLSQ upon awakening. We compared polysomnography
      results at the South Pole with sleep question responses on the LLSQ to assess
      their degree of correspondence. RESULTS: Twenty-two (30%) individuals reported no
      sleep problems whereas 20 (32%) reported some problems and 20 (33%) individuals
      reported poor sleep and 1 reported no sleep (n = 1). Median sleep efficiency was
      (94%) among response groups and mean overnight oxygen saturation was 81%. Median
      apnea hypopnea index (AHI; events/hour) was 10.2 in those who reported no
      problems sleeping, 5.1 in those reporting some problems sleeping, and 13.7 in
      those who reported poor sleep. These differences were not statistically
      significant. CONCLUSION: Self-reported sleep quality varied but there were no
      associated significant differences in sleep efficiency, overnight oxygen
      saturation, nor AHI. Studies that explore the role of objective sleep quality in
      the development of AMS should remove the sleep question on the LLSQ from AMS
      scoring algorithms.

PMID- 29172728
TI  - Diurnal variation and reliability of the urine lactate concentration after
      maximal exercise.
AB  - The postexercise urine lactate concentration is a novel valid exercise biomarker,
      which has exhibited satisfactory reliability in the morning hours under
      controlled water intake. The aim of the present study was to investigate the
      diurnal variation of the postexercise urine lactate concentration and its
      reliability in the afternoon hours. Thirty-two healthy children (11 boys and 21
      girls) and 23 adults (13 men and 10 women) participated in the study. All
      participants performed two identical sessions of eight 25 m bouts of maximal
      freestyle swimming executed every 2 min with passive recovery in between. These
      sessions were performed in the morning and afternoon and were separated by 3-4
      days. Adults performed an additional afternoon session that was also separated by
      3-4 days. All swimmers drank 500 mL of water before and another 500 mL after each
      test. Capillary blood and urine samples were collected before and after each test
      for lactate determination. Urine creatinine, urine density and body water content
      were also measured. The intraclass correlation coefficient was used as a
      reliability index between the morning and afternoon tests, as well as between the
      afternoon test and retest. Swimming performance and body water content exhibited
      excellent reliability in both children and adults. The postexercise blood lactate
      concentration did not show diurnal variation, showing a good reliability between
      the morning and afternoon tests, as well as high reliability between the
      afternoon test and retest. The postexercise urine density and lactate
      concentration were affected by time of day. However, when lactate was normalized
      to creatinine, it exhibited excellent reliability in children and good-to-high
      reliability in adults. The postexercise urine lactate concentration showed high
      reliability between the afternoon test and retest, independent of creatinine
      normalization. The postexercise blood and urine lactate concentrations were
      significantly correlated in all cases, attesting to the validity of urine lactate
      as an index of anaerobic metabolism. We conclude that urine lactate, after
      normalization to creatinine, could be used in training practice either in the
      morning or in the afternoon. Further research is needed to assess the
      applicability of this novel exercise biomarker.

PMID- 29172729
TI  - Association of insulin resistance and autonomic tone in patients with pregnancy
      induced hypertension.
AB  - Pregnancy-induced hypertension (PIH) remains the main cause of maternal and fatal
      mortality. Insulin resistance (IR) and autonomic nervous system (ANS) imbalance
      are two principal drivers of PIH development. Few previous researches
      investigated the association between IR and ANS imbalance in Chinese PIH
      patients. 120 pregnant women were enrolled in our study, sixty healthy pregnant
      women (control group), fourty one gestational hypertension (GH group) and
      nineteen preeclampsia patients (PE group). The homeostasis model assessment of IR
      (HOMA-IR) and markers of ANS (plasma biomarkers and heart rate variability (HRV)
      components) were collected. Body mass index (BMI), Ln(HOMA-IR), noradrenaline
      level, LnTP (total power), Ln SDNN (standard deviation of the normal-to-normal
      interval), LnLF (low frequency), LnLF/LnHF (low frequency/high frequency) were
      different in the GH and PE groups compared with the controls. Significant
      correlations were observed between Ln (HOMA-IR) and gestational duration (r =
      0.237, P = 0.031), BMI(r = 0.314, P = 0.002), systolic blood pressure (r = 0.108,
      P = 0.016), noradrenaline (r = 0.451, P = 0.009), LnTP (r = -0.269, P = 0.015)
      and LnLF/HF (r = 0.183, P = 0.026) in those PIH patients. Furthermore, BMI,
      noradrenaline and LnTP were independent determinants of Ln(HOMA-IR) in PIH
      patients by multiple regression analysis. Our finding verified both IR and ANS
      imbalance were more severe in PIH patients than healthy pregnant women. Moreover,
      IR had a close association with ANS parameters in PIH patients, suggesting that
      they probably had contributory effects on the occurrence and development of PIH.
      We propose that these parameters could be added to the traditional indexes for
      individualized treatment of PIH patients in the future.

PMID- 29172731
TI  - A verified bite by Heteroscodra maculata (Togo starburst or ornamental baboon
      tarantula) resulting in long-lasting muscle cramps.

PMID- 29172730
TI  - Renal sympathetic denervation lowers arterial pressure in canines with obesity
      induced hypertension by regulating GAD65 and AT1R expression in rostral
      ventrolateral medulla.
AB  - To explore the roles of glutamate acid decarboxylase 65 (GAD65) and angiotensin
      II type 1 receptor (AT1R) in the action of renal sympathetic denervation (RSD) on
      obesity-induced hypertension in canines. Thirty-two beagles were randomly divided
      into a hypertensive model (n = 22) and control (n = 10) groups. A hypertensive
      canine model was established by feeding a high-fat diet. Twenty hypertensive
      beagles were randomized equally to a sham-surgery and RSD-treated group receiving
      catheter-based radiofrequency RSD. Compared with the control group, the sham
      surgery group exhibited significant increases in blood pressure, serum
      angiotensin II level, rostral ventrolateral medulla (RVLM) glutamate level, and
      AT1R mRNA and protein expression and decreases in gamma-amino acid butyric acid
      (gamma-GABA) level and GAD65 mRNA and protein expression in the RVLM (all P <
      0.05). Treatment with RSD significantly attenuated the above abnormal alterations
      (all P < 0.05). Linear correlation analysis revealed that angiotensin II level
      was positively correlated with glutamate level (r = 0.804) and inversely
      correlated with gamma-GABA level (r = -0.765). GAD65 protein expression was
      positively correlated with gamma-GABA level (r = 0.782). Catheter-based
      radiofrequency RSD can decrease blood pressure in obesity-induced hypertensive
      canines. The antihypertensive mechanism might be linked to upregulation of GAD65
      and downregulation of AT1R in the RVLM.

PMID- 29172732
TI  - Effect of amlodipine, efonidipine, and trichlormethiazide on home blood pressure
      and upper-normal microalbuminuria assessed by casual spot urine test in essential
      hypertensive patients.
AB  - The aim of this study was to assess the effects of irbesartan alone and combined
      with amlodipine, efonidipine, or trichlormethiazide on blood pressure (BP) and
      urinary albumin (UA) excretion in hypertensive patients with microalbuminuria
      (30<=UA/creatinine (Cr) ratio [UACR] <300 mg/g Cr) and upper-normal
      microalbuminuria (10<=UACR<30 mg/g Cr). This randomized controlled trial enrolled
      175 newly diagnosed and untreated hypertensive patients (home systolic blood
      pressure [SBP]>=135 mmHg; 10<=UACR<300 mg/g Cr of casual spot urine at the first
      visit to clinic). All patients were treated with irbesartan (week 0). Patients
      who failed to achieve home SBP <=125 mmHg on 8-week irbesartan monotherapy
      (nonresponders, n = 115) were randomized into three additional drug treatment
      groups: trichlormethiazide (n = 42), efonidipine (n = 39), or amlodipine (n =
      34). Irbesartan monotherapy decreased home SBP and first morning urine samples
      (morning UACR) for 8 weeks (p < 0.0001). At 8 weeks after randomization, all
      three additional drugs decreased home SBP (p < 0.0002) and trichlormethiazide
      significantly decreased morning UACR (p = 0.03). Amlodipine decreased morning
      UACR in patients with microalbuminuria based on casual spot urine samples (p =
      0.048). However, multivariate analysis showed that only higher home SBP and UACR
      at week 8, but not any additional treatments, were significantly associated with
      UACR reduction between week 8 and week 16. In conclusion, crucial points of the
      effects of combination therapy on UACR were basal UACR and SBP levels. The effect
      of trichlormethiazide or amlodipine treatment in combination with irbesartan
      treatment on microalbuminuria needs to be reexamined based on a larger sample
      size after considering basal UACR and SBP levels.

PMID- 29172733
TI  - Nocturnal blood pressure decline based on different time intervals and long-term
      cardiovascular risk: the Ohasama Study.
AB  - A diminished nocturnal decline in blood pressure (BP) represents a risk factor
      for cardiovascular disease. To define daytime and nighttime ambulatory BP, clock
      time-dependent methods are used when information on diary-based sleeping time is
      unavailable. We aimed to compare fixed-clock intervals with diary records to
      identify nocturnal BP declines as a predictor of long-term cardiovascular risk
      among the general population. Data were obtained from 1714 participants with no
      history of cardiovascular disease in Ohasama, Japan (mean age, 60.6 years; 64.9%
      women). We defined extreme dippers, dippers, non-dippers, and risers as nocturnal
      systolic BP decline >=20%, 10-19%. 0-9%, and <0%, respectively. Over a mean
      follow-up period of 17.0 years, 206 cardiovascular deaths occurred. Based on
      diary records, multivariable-adjusted hazard ratios (HRs) for cardiovascular
      death compared with dippers were 1.24 (95% confidence interval [CI], 0.82-1.87)
      in extreme dippers, 1.21 (0.87-1.69) in non-dippers, and the highest HR of 2.31
      (1.47-3.62) was observed in risers. Using a standard fixed-clock interval
      (daytime 09:00-21:00; nighttime 01:00-06:00), a nighttime 2 h-early shifted fixed
      clock (daytime 09:00-21:00; nighttime 23:00-04:00), or a nighttime 2 h-late
      shifted fixed-clock (daytime 09:00-21:00; nighttime 03:00-08:00), the HR (95%CI)
      in risers compared with dippers was 1.57 (1.08-2.27), 2.02 (1.33-3.05), or 1.29
      (0.86-1.92), respectively. Although use of diary records remains preferable, the
      standard and nighttime 2 h-early shifted fixed-clock intervals appear feasible
      for population-based studies.

PMID- 29172734
TI  - Correlation between clinic, cumulative, 24h-ambulatory systolic blood pressure,
      and chronic kidney damage in Chinese elderly.
AB  - The aim of this study was to investigate whether clinic, cumulative, and 24h
      ambulatory systolic blood pressure (SBP) was associated with chronic kidney
      damage, defind as estimated glomerular filtration rate (eGFR) <60 ml/(min.1.73
      m2) and/or microalbuminuria >=30 mg/L, and, if so, which measurement of SBP is
      more associated with chronic kidney damage in Chinese elderly. A total of 1207
      participants older than 60 years old were included in the final analysis.
      Clinical blood pressure, cumulative blood pressure exposure was calculated and
      ambulatory 24h blood pressure was assessed. Multiple logistic regression analysis
      showed that the clinic (p < .001), cumulative (p = .033), 24h average (p < .001),
      daytime (p = .001) and nighttime SBP (p = .001) were respectively associated with
      lower eGFR, and cumulative (p = .008), 24 average (p < .001), daytime (p < .001),
      and nighttime SBP (p < .001) were the risk factors of microalbuminuria. The
      degree of correlation were strongest between 24h average SBP and chronic kidney
      damage (odds ratio, 1.78; 95% confidence interval, 1.46-2.15; p < .001), clinic
      SBP and eGFR (odds ratio, 1.57; 95% confidence interval, 1.13-2.17; p = .007),
      nighttime SBP and microalbuminuria (odds ratio, 1.45; 95% confidence interval,
      1.05-2.00; p = .024). The likelihood ratio test demonstrated that the
      introduction of 24h average SBP will improve the goodness of fit of the clinic
      SBP model(p < .05), while the introduction of cumulative SBP exposure has no such
      effect(p > .05). Cumulative SBP exposure seems inferior to other measurement in
      indentifying chronic kidney damage, including decreased GFR and microalbuminuria.

PMID- 29172735
TI  - Effects of Ganoderma, Rhodiola and grape seed extracts on the glucuronidation and
      oral bioavailability of resveratrol in rats.
AB  - Herb extracts were shown to inhibit the activity of UDP-glucuronosyltransferases
      (UGTs) in vitro. However, the actual in vivo effect of the inhibitory ability on
      oral bioavailability is yet verified. In this study, resveratrol (RES) was used
      as a model drug to study the effect of three Chinese herb extracts, Ganoderma,
      Rhodiola and grape seed, on the in vitro and in vivo inhibition of
      glucuronidation and the in vivo bioavailability of RES. Overall, although herb
      extracts might show inhibition on glucuronidation of RES in vitro and in vivo,
      the inhibition of glucuronidation did not necessarily mean to improve the in vivo
      bioavailability of RES.

PMID- 29172736
TI  - Role of Glial Cells in MU-Opioid Receptor-Mediated Vasodilation in the Rat
      Retina.
AB  - PURPOSE: Our recent study demonstrated that herkinorin, a non-opioid MU-receptor
      agonist derived from salvinorin A, dilates retinal arterioles through stimulation
      of MU-opioid receptors in rats. Activation of neuronal nitric oxide (NO) synthase
      and the presence of ganglion cells in the retina appear to be crucial for
      inducing MU-opioid receptor-mediated retinal vasodilation. In the present study,
      we examined the role of the interaction between neurons and glia in the retinal
      vasodilator mechanism involving MU-opioid receptors in rats. MATERIALS AND
      METHODS: The localization of MU-opioid receptors and neuronal NO synthase (nNOS)
      in the rat retina was examined using immunohistochemistry. The retinal vascular
      responses were evaluated by measuring the diameter of retinal arterioles in in
      vivo fundus images. Both systemic blood pressure and heart rate were continuously
      recorded. RESULTS: Immunoreactivity of MU-opioid receptors was found in ganglion
      cells and astrocytes, while that of nNOS was detected in ganglion cells and
      amacrine cells. Herkinorin increased retinal arteriolar diameter without
      significantly changing mean blood pressure and heart rate. The retinal
      vasodilator response to herkinorin was significantly attenuated by treatment with
      glial toxins (fluorocitrate and disialoganglioside-GD1b). The glial toxins
      markedly prevented vasodilation induced by intravitreal injection, but not by
      intravenous infusion, of NOR3, an NO donor. CONCLUSION: These results suggest
      that retinal glial cells play an important role in the MU-opioid receptor
      mediated retinal vasodilation in rats. Stimulation of MU-opioid receptors on
      retinal ganglion cells may affect the activity of glial cells, thereby changing
      retinal vascular tone.

PMID- 29172737
TI  - Relationship between shift work schedule and self-reported sleep quality in
      Chinese employees.
AB  - Few studies have reported on the effects of fixed and rotating shift systems on
      the prevalence of sleep disturbance. Thus, in this study, the relationships
      between different work schedules and sleep disturbance in Chinese workers were
      investigated. A total of 2180 workers aged 19-65 years responded to the self
      report questionnaire on shift work schedule (fixed day-shift, fixed night-shift,
      two-shift or three-shift system), working hours a day, and working days a week,
      physical effort, subjective sleep quality and subjective mental state. It was
      found that the rotating shift workers, namely, two- and three-shift workers,
      exhibited higher risks of sleep disturbance than with the fixed day-shift workers
      did (OR 1.37; 95% CI 1.07to 1.74; and OR 2.19; 95% CI 1.52 to 3.15,
      respectively). The risk was particularly high among two- or three-shift workers
      who worked more than 8 hours a day or more than 5 days a week and among three
      shift workers who reported both light and heavy physical effort at work.
      Moreover, the two- and three-shift workers (rotating shift workers) suffered from
      poorer sleep quality than the fixed night shift workers did (OR 1.84; 95% CI 1.01
      to 3.32; and OR 2.94; 95% CI 1.53 to 5.64, respectively). Consequently, rotating
      shift work (two- and three-shift work) is a risk factor for sleep disturbance,
      and the fixed work rhythm may contribute to the quality of sleep.

PMID- 29172738
TI  - Authors' response to letter on "levetiracetam in toxic seizures".

PMID- 29172739
TI  - Effect of aquatic exercise on mental health, functional autonomy, and oxidative
      dysfunction in hypertensive adults.
AB  - The aquatic exercise is an effective non-pharmacological therapy for prevention
      and control of hypertension. The objective of the present study was to
      investigate the effect of aquatic exercise on mental health, functional autonomy,
      and oxidative dysfunction in hypertensive adults. Methodologically 29 adults
      (mean age 53 +/- 7.5 years) were included in the study, and were randomly grouped
      as hypertensive (n = 16) and non-hypertensive (n = 13). Both groups underwent low
      intensity aquatic exercise program for 12 weeks. Outcomes were evaluated at week
      0 and 12. The values for the following parameters decreased in the hypertensive
      group post training: anxiety (-6.2 +/- 2 score; 60%), Timed Up and Go test (-7.4
      +/- 0.3 sec; 30%), protein carbonylation (-0.15 +/- 0.03 nmol/mg protein; 50%),
      nitric oxide (12.4 +/- 6 nmol/mg protein; 62%), interleukin-6 (-27.6 +/- 5.7
      pg/mg protein; 46%), and tissue necrosis factor-alpha (-52.4 +/- 3.8 pg/mg
      protein; 40%); however, the values of the following parameters increased before
      training: Berg score (56 +/- 2; 7.8%), flexibility (27 +/- 1 cm; 71%);
      glutathione (3.1 +/- 1.3 nmol/mg protein; 138%), and superoxide dismutase (1.6 +/
      0.4 nmol/mg; 166%). In conclusion, we suggest that low-intensity aquatic
      exercise program improved anxiety, functional autonomy, and oxidative dysfunction
      in hypertensive adults.

PMID- 29172740
TI  - The choroid plexus harbors a circadian oscillator modulated by estrogens.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus is considered the master
      circadian oscillator in mammals. However, extra-SCN structures in the brain also
      display daily rhythms. Recently, we have demonstrated that the choroid plexus
      (CP) expresses core clock genes that are subjected to circadian regulation in a
      sex-dependent manner. By using CP explants cultured from female knock-in mice
      carrying the Period-luciferase transgene, we show that CP exhibits endogenous
      circadian rhythms of PERIOD2::LUCIFERASE expression. Furthermore, we demonstrate
      that estrogen declines following ovariectomy modulates the daily rhythm
      expression of Bmal1, Per1 and Per2 in female rat CP, corroborating data obtained
      in experiments where rat CP epithelial cell (CPEC) cultures were incubated with
      17beta-estradiol (E2). The molecular mechanism underlying these effects was also
      investigated, and we provide evidence that the estrogen receptor (ER) mediates
      the response of clock genes to E2. In conclusion, our study proves that the CP
      harbors a circadian oscillator that is modulated by estrogens and demonstrates
      that E2 regulation occurs through an estrogen-receptor-dependent mechanism.

PMID- 29172741
TI  - Effects of Intravitreal Aflibercept on Galectin-1 and Vascular Endothelial Growth
      Factor-A Plasma Levels in Patients with Diabetic Retinopathy.
AB  - PURPOSE: To analyze the interaction between aflibercept and galectin-1 and
      evaluate the plasma levels of galectin-1 and vascular endothelial growth factor
      (VEGF)-A after intravitreal injection of aflibercept in patients with diabetic
      retinopathy (DR). METHODS: Interaction of galectin-1 with aflibercept was
      determined via immunoprecipitation. Seventeen patients with type 2 diabetes and
      diabetic macular edema (DME) were each treated with a single intravitreal
      injection of aflibercept (2.0 mg, 50 uL) monthly for three consecutive months.
      Plasma galectin-1 and VEGF-A levels were measured just before an injection was
      administered, 1 week after the first injection, and 2 months after the last
      injection. Nineteen age- and sex-matched healthy participants served as controls.
      RESULTS: Irrespective of the tested galectin-1 concentration, 24% of added
      galectin-1 was precipitated by aflibercept. Baseline plasma concentrations of
      galectin-1 were 22.0 and 23.0 ng/mL in the control and aflibercept-treated
      groups, respectively. Systemic galectin-1 levels increased to 27.0 and 24.0 ng/mL
      at 7 days and 4 weeks, respectively, after treatment. At week 8, plasma galectin
      1 levels significantly increased to 36.0 ng/mL. This level persisted for 20
      weeks. Systemic VEGF-A levels significantly reduced to below the minimum
      detectable dose in 16 DME patients at 7 days after treatment. This level
      persisted for 4 weeks. Plasma VEGF-A levels were reduced at weeks 8 (p = 0.099)
      and 20 (p = 0.023). Decreased plasma VEGF-A levels were observed in all patients
      after treatment. CONCLUSION: We confirmed that physiological aflibercept levels
      precipitate galectin-1 in in vitro assays. Additionally, systemic upregulation of
      galectin-1 might be induced by intravitreal aflibercept, which may be relevant in
      the clinical outcomes of DR treatment.

PMID- 29172742
TI  - The risk of right ventricular failure with current continuous-flow left
      ventricular assist devices.
AB  - INTRODUCTION: Right ventricular failure (RVF) still results as the major cause of
      morbidity and mortality after left ventricular assist device (LVAD) implantation.
      Despite overall improved outcomes and lower rates of RVF with the use of the
      newer, continuous-flow (CF) LVADs over pulsatile-flow devices, and development of
      clinical prediction scores to facilitate preoperative identification of patients
      at risk for RVF after implantation, RVF occurs in 13% to 40% of continuous-flow
      device. Areas covered: In this article, a review has been carried out on the
      current evidence for preoperative assessment of RV function and RVF risk for
      appropriate patient selection mainly focusing on current imaging and invasive
      assessment tools. Expert commentary: According to all findings, it is recommended
      that measurements of RV function should be included in all risk predictions
      models and that standardization of echocardiographic and hemodynamic evaluation
      protocols be adopted before and after device implantation across LVAD centers.
      The balance of well-accepted and fixed multiple variables might be able to better
      predict the outcomes in such a delicate clinical panorama.

PMID- 29172744
TI  - Identification of mothball powder composition by float tests and melting point
      tests.
AB  - INTRODUCTION: The aim of the study was to identify the composition, as either
      camphor, naphthalene, or paradichlorobenzene, of mothballs in the form of powder
      or tiny fragments by float tests and melting point tests. METHODS: Naphthalene,
      paradichlorobenzene and camphor mothballs were blended into powder and tiny
      fragments (with sizes <1/10 of the size of an intact mothball). In the float
      tests, the mothball powder and tiny fragments were placed in water, saturated
      salt solution and 50% dextrose solution (D50), and the extent to which they
      floated or sank in the liquids was observed. In the melting point tests, the
      mothball powder and tiny fragments were placed in hot water with a temperature
      between 53 and 80  degrees C, and the extent to which they melted was observed.
      Both the float and melting point tests were then repeated using intact mothballs.
      Three emergency physicians blinded to the identities of samples and solutions
      visually evaluated each sample. RESULTS: In the float tests, paradichlorobenzene
      powder partially floated and partially sank in all three liquids, while
      naphthalene powder partially floated and partially sank in water. Naphthalene
      powder did not sink in D50 or saturated salt solution. Camphor powder floated in
      all three liquids. Float tests identified the compositions of intact mothball
      accurately. In the melting point tests, paradichlorobenzene powder melted
      completely in hot water within 1 min while naphthalene powder and camphor powder
      did not melt. The melted portions of paradichlorobenzene mothballs were sometimes
      too small to be observed in 1 min but the mothballs either partially or
      completely melted in 5 min. Both camphor and naphthalene intact mothballs did not
      melt in hot water. CONCLUSIONS: For mothball powder, the melting point tests were
      more accurate than the float tests in differentiating between paradichlorobenzene
      and non-paradichlorobenzene (naphthalene or camphor). For intact mothballs, float
      tests performed better than melting point tests. Float tests can identify camphor
      mothballs but melting point tests cannot. We suggest melting point tests for
      identifying mothball powder and tiny fragments while float tests are recommended
      for intact mothball and large fragments.

PMID- 29172743
TI  - Impact of hyperhomocysteinemia on insulin resistance in patients with H-type
      hypertension.
AB  - BACKGROUND: Hypertension (HT) and hyperhomocysteinemia (HHcy) had been considered
      influential factors of insulin resistance. H-type HT occurred as HHcy associated
      with HT. The impact of HHcy on insulin resistance in H-type HT patients remains
      to be estimated. The interacted effects of HHcy and HT on insulin resistance are
      still unclear. METHODS: A total of 790 patients were recruited and classified
      into four groups according to their blood pressure and plasma Hcy level, i.e.,
      control group (C group), HHcy group (HHcy subjects without HT), HT group (HT
      subjects without HHcy), and H group (subjects with H-type HT). The relationship
      between HHcy and insulin resistance, as estimated using the HOMA-IR, was analyzed
      and related to blood pressure. RESULTS: HOMA-IR values were significantly higher
      in the HHcy group than the C group (2.97 (2.23-4.01) versus 2.54 (1.87-3.58), P <
      0.01). H-type HT patients showed more severe insulin resistance than those who
      only got HT (3.58 (2.59-4.85) versus 2.96 (1.90-3.49),P < 0.01). Moreover, HOMA
      IR values were positively correlated with Hcy levels (r = 0.26, P < 0.01). After
      correcting for possible risking factors, a linear regression relationship between
      insulin resistance and HHcy was found (beta = 0.158, P < 0.01). HHcy was
      interacted with HT on the exacerbation of insulin resistance in H-type HT
      patients (beta = 0.501, P < 0.01). CONCLUSIONS: HHcy obviously exacerbate insulin
      resistance, especially in H-type HT patients. HHcy and HT have a multiplicative
      effect on metabolic dysfunction, which may help to interpret why these patients
      are suffering a high risk of cardiovascular disease and stroke.

PMID- 29172745
TI  - Association of ACE gene A2350G and I/D polymorphisms with essential hypertension
      in the northernmost province of China.
AB  - Angiotensin converting enzyme (ACE) gene, as a strong candidate gene for
      essential hypertension(EH), has been extensively studied. In this study, we
      carried out a population-based case-control study to explore whether ACE gene I/D
      and A2350G polymorphisms could consider to be risk factors for EH. A total of
      2040 subjeces were recruited from Chinese Han in this study, out of which 1010
      were cases and 1030 were normotensive individuals. ACE gene A2350G and I/D
      polymorphisms were amplified by polymerase chain reaction (PCR) and A2350G
      polymorphism was detected after restriction enzyme digestion with BstuI. Besides,
      we choosed 10% samples randomly sequencing to verify the accuracy of results.
      Genotype and allele frequencies distribution of I/D and A2350G in EH and control
      groups were significantly different. After grouped by sex or age, there were
      still statistical significances for two polymorphisms. In dominant and recessive
      model of A2350G, we found significant differences between two groups,
      respectively. For ACE I/D polymorphism, we observed that the existence of
      dramatical difference in dominant model between two groups, while in recessive
      model, marginally significant difference was found. Among the four haplotypes
      composed by ACE gene A2350G and I/D, haplotype G-D reached the statistical
      significance in two groups, and exhibited to be a risk factor for the development
      of EH, whose P < 0.001 and OR 95%CI = 1.639(1.435-1.872), while the other
      haplotypes were the protective factors and decreased the susceptibility to EH(P <
      0.05). ACE gene A2350G and I/D polymorphisms were associated with increasing the
      risk of suffering from EH in the northernmost province of China individuals, with
      D allele and G allele individuals had a higher risk of EH(OR = 1.443, 95%CI =
      1.273-1.636 and OR = 1.481, 95%CI = 1.303-1.684).

PMID- 29172750
TI  - Parallel short forms for the assessment of activities of daily living in
      cardiovascular rehabilitation patients (PADL-cardio): development and validation.
AB  - PURPOSE: To develop and validate parallel short forms for the assessment of
      activities of daily living in cardiac rehabilitation patients (PADL-cardio I &
      II). METHOD: PADL-cardio I & II were developed based on a sample of 106 patients
      [mean age  =  57.6; standard deviation (SD) = 11.1; 72.6% males] using Rasch
      analysis and validated with a sample of 81 patients (mean age  =  59.1; SD  = 
      11.1; 88.9% males). All patients answered PADL-cardio and the Short Form 12
      Health Survey. RESULTS: Both versions of PADL-cardio are composed of 10 items.
      The fit to the Rasch model was given documented by a non-significant Item-trait
      interaction score (PADL-cardio I: chi2 = 31.08, df  =  30, p  =  0.41; PADL
      cardio II: chi2 = 45.6, df  =  40, p  =  0.25). The two versions were free of
      differential item functioning. Person-separation reliability was 0.72/0.78 and
      unidimensionality was given. The two versions correlated with r = 0.98 and the
      correlation between PADL-cardio and the underlying item bank was 0.99 for both
      versions. Concurrent validity is indicated through correlations with the Short
      Form 12 Health Survey (r  = -0.37 to -0.40). CONCLUSION: PADL-cardio provides a
      short and psychometrically sound option for the assessment of activities of daily
      living in cardiovascular rehabilitation patients. The two versions of PADL-cardio
      are equivalent. Hence, they can be used to reduce practice and retest effects in
      repeated measurement, facilitating the longitudinal assessment of activities of
      daily living. Implications for Rehabilitation New parallel test forms for the
      assessment of activities of daily living in cardiac rehabilitation (PADL-cardio I
      & PADL-cardio II) are available. PADL-cardio I & II consist of 10 items and are
      therefore especially timesaving. Concurrent validity is given through
      correlations with the Short Form Health Survey 12. Therapeutic success could be
      determined more precisely by the parallel forms reducing practice and retest
      effects.

PMID- 29172746
TI  - Pazopanib for renal cell carcinoma leads to elevated mean arterial pressures in a
      murine model.
AB  - BACKGROUND: In the setting of metastatic RCC (mRCC), pazopanib is approved as
      first line therapy. Unfortunately treatment may lead to cardiotoxicity such as
      hypertension, heart failure, and myocardial ischemia. OBJECTIVE: Define the in
      vivo role of pazopanib in the development of cardiotoxicity. METHODS: Wild type
      mice were dosed for 42 days via oral gavage, and separated into control and
      treatment (pazopanib) groups. Baseline ECG's, echocardiograms, and blood
      pressures were recorded. At the conclusion of the study functional parameters
      were again recorded, and animals were used for pathological, histological, and
      protein analysis. RESULTS: After 2 weeks of dosing with pazopanib, the treatment
      group exhibited a statistically significant increase in mean arterial pressure
      compared to control mice (119 +/- 11.7 mmHg versus 108 +/- 8.2 mmHg, p = 0.049).
      Treatment with pazopanib led to a significant reduction in the cardiac output of
      mice. CONCLUSION: Our findings in mice clearly demonstrate that treatment with
      pazopanib leads to a significant elevation in blood pressure after 2 weeks of
      dosing and this persists for the duration of dosing. The continued development of
      the cardio-oncology field will be paramount in providing optimal oncologic care
      while simultaneously improving cardiac outcomes through further investigation
      into the mechanisms of CV toxicity.

PMID- 29172749
TI  - Reduction-responsive PEtOz-SS-PCL micelle with tailored size to overcome blood
      brain barrier and enhance doxorubicin antiglioma effect.
AB  - A series of novel reduction-responsive micelles with tailored size were designed
      and prepared to release doxorubicin (DOX) for treating glioma, which were
      developed based on amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-b-poly
      (epsilon-caprolactone) (PEtOz-SS-PCL) and the micelle size could be regulated by
      designing the polymer structure. The DOX-loaded PEtOz-SS-PCL micelles had small
      size and rapid drug release in reductive intracellular environments.
      Biodistribution and in vivo imaging studies in C6 glioma mice tumor model showed
      that DOX loaded PEtOz-SS-PCL43 micelles with the smallest size had superior
      accumulation and fast drug release in tumor sites. In vivo antitumor activity
      demonstrated that DOX-loaded PEtOz-SS-PCL43 micelles improved antitumor efficacy
      in contrast to PEtOz-SS-PCL micelles with larger size toward the orthotopic C6
      Luci cells-bearing mice. This study shows great potential in tailoring the
      micelle size and introducing the responsive bonds or compartment for
      intracellular drug delivery and release in glioma treatment by designing the
      architecture of the polymer.

PMID- 29172752
TI  - Correction to: Loft et al., 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.

PMID- 29172751
TI  - "This one will delay us": barriers to accessing health care services among
      persons with disabilities in Malawi.
AB  - PURPOSE: This paper explores the barriers which people with disabilities
      experience in accessing health care services in Malawi. METHODOLOGY: Fifty-two in
      depth interviews were conducted with people with various types of disabilities.
      These interviews were conducted in four districts in Malawi: Blantyre and
      Phalombe in the Southern Region; Ntchisi in the Central Region, and Rumphi in the
      North. A team of trained research assistants conducted the interviews. RESULTS:
      The major challenges that people with disabilities experience include the cost of
      accessing health care, long distances to health facilities, lack of transport,
      hilly terrains and flooding of rivers during the rainy season, communication
      challenges with the health providers and poor attitude of health workers. Some of
      these challenges are not unique to people with disabilities, but constitute more
      of a problem among people with disabilities. CONCLUSION: There is a need to
      address these challenges through the expansion of the provision of assistive
      devices, implementing comprehensive outreach services targeting people with
      disabilities and strengthening the links between key component of access to
      quality health care. Attitudinal barriers and lack of resources remain major
      challenges. Implications for rehabilitation Though people with disabilities face
      challenges accessing health care world-wide, the challenges are greater in low
      income countries. The current study in Malawi confirms this. Major challenges
      include costs of care, transport costs, and inaccessible facilities. Lack of
      health worker awareness and attitudinal barriers are major issues of concern. It
      is imperative, given this situation, that effort is spent in Malawi and similar
      contexts on dealing with issues of stigma and discrimination especially in the
      health care sector. It is also important to explore cost-effective ways of
      assisting people with disabilities accessing appropriate transport, which should
      be seen as part of the healthcare system. Though the cost of providing equitable
      care may be high in low-income contexts, this is a human right. Training and
      creating an accessible and disability-friendly service environment is a key
      priority.

PMID- 29172753
TI  - Design and characterization of calcium-free in-situ gel formulation based on
      sodium alginate and chitosan.
AB  - The aim of this study was to prepare and evaluate calcium-free sustained release
      drug delivery systems, based on the in-situ gelation of oral suspensions
      containing chitosan, sodium alginate and Ranitidine as drug model. The combined
      effects of polymer concentrations and their interactions on the rheological
      characteristics of both gels and suspensions and, on the kinetics of drug release
      were evaluated by using a central composite face-centered design. Rheological
      analysis showed that suspensions were potentially stable, with a viscosity
      increased by 1000 times compared to that of water. In addition, the obtained gels
      were consistent; their storage modulus could reach values close to 50 kPa when
      alginate concentration was greater than 7.5 g/100 mL and chitosan was fixed to
      0.5 g/100 mL. In these conditions gels should have a higher gastric residence
      time, in comparison to the standard gastric emptying time (~2 h). Evaluation of
      the in-vitro release kinetics of Ranitidine showed that the association of the
      lowest concentration of chitosan (0.5 g/100 mL) with higher alginate
      concentrations generates sustained release kinetics profiles. The time
      corresponding to 63% of release was found close to 1.5 h, in which case the
      process is governed by Fickian diffusion. Finally, calcium-free alginate-chitosan
      based on the in-situ gelation of suspensions is advantageous as a drug delivery
      system for sustained-release.

PMID- 29172755
TI  - Demographic and clinical features of atrial myxomas: A case series analysis.
AB  - AIM: Cardiac myxomas are uncommon tumors and have a wide clinical spectrum. Their
      diagnosis can therefore be elusive because symptoms are nonspecific and
      misleading. Our aim was to characterize and analyze the clinical findings in
      patients presenting with cardiac myxomas. METHODS: We conducted a retrospective,
      hospital-based case study using the electronic records of a Spanish general
      hospital, caring for a population of 155,000. Patients' data were collected for
      the period between 2000 and 2016. Demographic data and clinical features were
      analyzed. RESULTS: Our series included 22 patients over a 15-year period (annual
      incidence of 0.94 patients per 100,000 inhabitants). Men were predominant (68%)
      and the median age was 69 years. Cardiac (40.9%), systemic (27.3%), and
      neurological manifestations (13.6%) were the main clinical features. Left atrium
      (81.8%) was the predominant location. Surgical treatment was performed in all
      patients and the overall outcome was good in all cases. CONCLUSIONS: Cardiac
      myxomas are uncommon, benign tumors, predominantly located in the left atrium and
      mainly affecting middle-aged and elderly male patients. Congestive heart failure,
      stroke, and systemic symptoms, although misleading and nonspecific, are the most
      frequent forms of clinical presentation.

PMID- 29172756
TI  - The experience of parents of adult sons with Duchenne muscular dystrophy
      regarding their prolonged roles as primary caregivers: a serial qualitative
      study.
AB  - PURPOSE: Mechanical ventilation has allowed a greater number of patients with
      Duchenne muscular dystrophy (DMD) to transition into adulthood. However, the role
      of a child's parent as a caregiver lasts throughout the child's lifetime. We
      explored parents' experiences of prolonged caregiving using serial interviews,
      analyzed using constructivist grounded theory. MATERIALS AND METHODS: Fourteen
      parents (average age 53.9 years) with sons with DMD (average age 23.2 years) were
      interviewed two to four times, over a 3-year period. Data were analyzed using a
      grounded theory approach. RESULTS: Two categories of responses were defined as
      strengths, and four as weaknesses. The strengths were related to family member
      support and confidence in parenting ability. The weaknesses were related to the
      anticipation of aging with the ongoing burden of caring for adult sons, regrets,
      sharing of responsibility versus having a fixed role as the primary caregiver,
      and economic burden. The weaknesses became more pronounced as the duration of
      caregiving increased. Parents' acceptance of and immobilization in their role of
      primary caregiver led to prolonged derivative dependency. CONCLUSION: Practical
      support for parental caregivers, who experience a marked increase in the duration
      of their caregiving role while facing their own aging-related challenges, are
      required. Implications for Rehabilitation Children with DMD are living longer and
      are transitioning into adulthood; a successful transition involves becoming as
      independent as possible and maintaining a positive sense of personal identity.
      Despite entering adulthood, the parental caregiver's caregiving role continues.
      Rehabilitation professionals, who are able to provide long-term, continued
      support from childhood into adulthood, should be aware that parental caregivers'
      weakness are exacerbated as the duration of caregiving increases. Families
      affected by DMD require multifaceted support that should include support for the
      parental caregiver.

PMID- 29172757
TI  - Systemic effects of angiogenesis inhibition alter pharmacokinetics and
      intratumoral delivery of nab-paclitaxel.
AB  - Angiogenesis is critical to the growth of tumors. Vascularization-targeting
      agents, with or without cytotoxic drugs, are widely used for the treatment of
      several solid tumors including esophagogastric adenocarcinoma. However, little is
      known about the systemic effects of anti-angiogenic therapies and how this
      affects the pharmacokinetics and intratumoral delivery of cytotoxic agents. In
      this study, patient-derived xenograft mouse models of esophageal adenocarcinoma
      were used to identify the effects of DC101, a murine vascular endothelial growth
      factor receptor 2 (VEGFR2) inhibitor, on the pharmacokinetics and the
      intratumoral uptake of nab-paclitaxel (NPTX). We showed that DC101 had large
      systemic effects resulting in decreased vasculature of intraperitoneally located
      organs. As a consequence, after intraperitoneal administration of NPTX, plasma
      uptake (5.029 +/- 4.35 vs. 25.85 +/- 2.27 uM) and intratumoral delivery (5.48 +/-
      5.32 vs. 38.49 +/- 2.805 pmol/mg) of NPTX were greatly impaired in DC101-treated
      animals compared to control animals. Additionally, routes of NPTX elimination
      were altered upon angiogenesis inhibition; unchanged renal clearance and
      intraperitoneal accumulation of NPTX were observed, but NPTX levels were
      significantly lower in the liver. Histological examination of the intestine
      revealed a reduced thickness of the intestinal wall following DC101 therapy and
      suggested seepage of intraperitoneally injected NTPX through the intestinal wall
      to explain its reduced uptake in liver, plasma, and tumor tissue. These data
      explain several adverse effects observed in the clinic when using anti-angiogenic
      therapies and also imply that the combined use of anti-angiogenesis and cytotoxic
      agents in both preclinical and clinical setting is still suboptimal.

PMID- 29172758
TI  - Deformity and Clinical Outcomes Following Operative Correction of Charcot Foot: A
      New Classification With Implications for Treatment.
AB  - BACKGROUND: The historic treatment of Charcot foot arthropathy has been
      immobilization during the active phase of the disease process, followed by
      accommodative bracing of the acquired deformity. Evidence derived from modern
      patient-reported outcomes investigations has convinced many surgeons to attempt
      operative correction of the acquired deformity with a goal of improving quality
      of life. METHODS: Over a 12-year period, 214 patients (9 bilateral) underwent
      reconstruction of the acquired deformity associated with midtarsal Charcot foot
      arthropathy. Over time, 3 patterns of deformity were observed based on weight
      bearing pattern, relationship of the forefoot to the hindfoot, and integrity of
      the talocalcaneal joint. A valgus deformity pattern was present in 138, varus in
      48, and dislocation of the talocalcaneal joint in 37. A consistent operative
      strategy was employed. Surgery included percutaneous tendon-Achilles lengthening,
      resection of infection when present, attempted correction of the structural
      deformity by wedge resection at the apex of the deformity, and immobilization
      with a 3-level static circular external fixator. Additional deformity pattern
      specific procedures were added over time. Clinical outcomes were based on the
      historic metrics of limb salvage and resolution of infection and the functional
      metric of the ability to walk with commercially available therapeutic footwear.
      RESULTS: Seven patients died within a year of surgery, and 15 underwent partial-
      or whole-foot amputation. Overall, 173 of 223 feet (77.6%) achieved a favorable
      clinical outcome. Patients with a valgus deformity pattern were most likely to
      achieve a favorable clinical outcome (120 of 138, 87.0%). Patients with a
      dislocation pattern were less likely to achieve a favorable clinical outcome (26
      of 37, 70.3%), and those with a varus deformity pattern were least likely to
      achieve a favorable clinical outcome (27 of 48, 56.3%). CONCLUSIONS: Operative
      correction of the acquired deformity of Charcot foot arthropathy was performed
      with a goal of improving quality of life. Stratification of patients by deformity
      pattern allowed alterations of the basic surgery to afford improved outcomes. In
      addition to achieving historic goals of resolution of infection and limb salvage,
      almost 80% of the patients were able to achieve the functional goal of
      independent ambulation with commercially available therapeutic footwear. The
      clinical outcomes achieved in this retrospective case series appear to support
      the modern paradigm of operative correction of deformity in this complex patient
      population. This realistic appreciation of outcome expectations should both be
      helpful in counseling patients on the risk-benefit ratio associated with surgery
      and provide a benchmark to measure newer strategies of treatment. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 29172759
TI  - Co-delivery of gambogic acid and TRAIL plasmid by hyaluronic acid grafted PEI
      PLGA nanoparticles for the treatment of triple negative breast cancer.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based combination
      therapy and gene therapy are new strategies to potentially overcome the
      limitations of TRAIL, however, the lack of efficient and low toxic vectors
      remains the major obstacle. In this study, we developed a hyaluronic acid (HA)
      decorated polyethylenimine-poly(d,l-lactide-co-glycolide) (PEI-PLGA) nanoparticle
      (NP) system for targeted co-delivery of TRAIL plasmid (pTRAIL) and gambogic acid
      (GA) in triple-negative breast cancer (TNBC) therapy. GA was encapsulated into
      the core of the PEI-PLGA NPs while pTRAIL was adsorbed onto the positive NP
      surface via charge adsorption. The coating of HA on PEI-PLGA NPs functions as a
      targeting ligand by binding to CD44 receptor of TNBC cells and a shell to
      neutralize the excess positive charge of inner NPs. The resultant pTRAIL and GA
      co-loaded HA-coated PEI-PLGA NPs exhibited spherical shape (121.5 nm) and could
      promote the internalization of loaded cargoes into TNBC cells through the CD44
      dependent endocytic pathway. The dual drug-loaded NPs significantly augmented
      apoptotic cell death in vitro and inhibited TNBC tumor growth in vivo. This
      multifunctional NP system efficiently co-delivered GA and pTRAIL, thus
      representing a promising strategy to treat TNBC and bringing forth a platform
      strategy for co-delivery of therapeutic DNA and chemotherapeutic agents in
      combinatorial TNBC therapy.

PMID- 29172760
TI  - Adjusted comparison of daratumumab monotherapy versus real-world historical
      control data from the Czech Republic in heavily pretreated and highly refractory
      multiple myeloma patients.
AB  - OBJECTIVES: We conducted an adjusted comparison of progression-free survival
      (PFS) and overall survival (OS) for daratumumab monotherapy versus standard of
      care, as observed in a real-world historical cohort of heavily pretreated
      multiple myeloma patients from Czech Republic. METHODS: Using longitudinal chart
      data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma
      Group, patient-level data from the RMG was pooled with pivotal daratumumab
      monotherapy studies (GEN501 and SIRIUS; 16 mg/kg). RESULTS: From the RMG
      database, we identified 972 treatment lines in 463 patients previously treated
      with both a proteasome inhibitor and an immunomodulatory drug. Treatment
      initiation dates for RMG patients were between March 2006 and March 2015. The
      most frequently used treatment regimens were lenalidomide-based regimens (33.4%),
      chemotherapy (18.1%), bortezomib-based regimens (13.6%), thalidomide-based
      regimens (8.0%), and bortezomib plus thalidomide (5.3%). Few patients were
      treated with carfilzomib-based regimens (2.5%) and pomalidomide-based regimens
      (2.4%). Median observed PFS for daratumumab and the RMG cohort was 4.0 and 5.8
      months (unadjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.94
      1.39), respectively, and unadjusted median OS was 20.1 and 11.9 months
      (unadjusted HR, 0.61; 95% CI, 0.48-0.78), respectively. Statistical adjustments
      for differences in baseline characteristics were made using patient-level data.
      The adjusted HRs (95% CI) for PFS and OS for daratumumab versus the RMG cohort
      were 0.79 (0.56-1.12; p = .192) and 0.33 (0.21-0.52; p < .001), respectively.
      CONCLUSIONS: Adjusted comparisons between trial data and historical cohorts can
      provide useful insights to clinicians and reimbursement decision makers on
      relative treatment efficacies in the absence of head-to-head comparison studies
      for daratumumab monotherapy.

PMID- 29172761
TI  - A longitudinal interprofessional simulation curriculum for critical care teams:
      Exploring successes and challenges.
AB  - Interprofessional care teams are the backbone of intensive care units (ICUs)
      where severity of illness is high and care requires varied skills and experience.
      Despite this care model, longitudinal educational programmes for such workplace
      teams rarely include all professions. In this article, we report findings on the
      initial assessment and evaluation of an ongoing, longitudinal simulation-based
      curriculum for interprofessional workplace critical care teams. The study had two
      independent components, quantitative learner assessment and qualitative
      curricular evaluation. To assess curriculum effectiveness at meeting learning
      objectives, participant-reported key learning points identified using a self
      assessment tool administered immediately following curricular participation were
      mapped to session learning objectives. To evaluate the curriculum, we conducted a
      qualitative study using a phenomenology approach involving purposeful sampling of
      nine curricular participants undergoing recorded semi-structured interviews.
      Verbatim transcripts were reviewed by two independent readers to derive themes
      further subdivided into successes and barriers. Learner self-assessment
      demonstrated that the majority of learners, across all professions, achieved at
      least one intended learning objective with senior learners more likely to report
      team-based objectives and junior learners more likely to report
      knowledge/practice objectives. Successes identified by curricular evaluation
      included authentic critical care curricular content, safe learning environment,
      and team comradery from shared experience. Barriers included unfamiliarity with
      the simulation environment and clinical coverage for curricular participation.
      This study suggests that a sustainable interprofessional curriculum for workplace
      ICU critical care teams can achieve the desired educational impact and
      effectively deliver authentic simulated work experiences if barriers to
      educational engagement and participation can be overcome.

PMID- 29172762
TI  - Cultural Guides, Cultural Critics: Distrust of Doctors and Social Support during
      Mental Health Treatment.
AB  - Research on relationships and health often interprets culture as the passively
      transmitted "content" of social ties, an approach that overlooks the influence of
      cultural resources on relationships themselves. I propose that mental health
      patients seek social support partly based on cultural resources held by their
      network members, including members' medical knowledge and beliefs. I test
      hypotheses using data from the Indianapolis Network Mental Health Study, an
      egocentric network survey of new mental health patients ( N = 152) and their
      personal relationships ( N = 1,868). Results from random-intercept regressions
      show that patients obtain support from network members who trust doctors and who
      have experience with mental problems. In contrast, network members who distrust
      doctors disproportionately cause problems for patients. I discuss how cultural
      resources can categorize network members as supportive cultural guides or
      disruptive cultural critics. Reconsidering how culture shapes relationships
      clarifies the role of networks during illness management and illustrates their
      potentially harmful effects.

PMID- 29172763
TI  - Depression, Work and Family Roles, and the Gendered Life Course.
AB  - Despite the importance of employment for shaping mental health over the life
      course, little is known about how the mental health benefits of employment change
      as individuals age through their prime employment and child-rearing years. This
      study examines the National Longitudinal Survey of Youth, 1979 Cohort ( N =
      8,931), following respondents from their late 20s to mid-50s. Results suggest
      that among women, the aging of children is especially salient for shaping the
      mental health consequences of employment. Young children diminish the protective
      effect of mothers' full- and part-time employment, but the salubrious effects of
      paid work increase as children get older. The benefit of employment for men's
      mental health also changes over time, but it is the aging of men themselves
      rather than their children that alters the magnitude of full-time employment's
      protective effect. Findings suggest the contribution of employment to life course
      mental health remains tethered to traditional gender roles.

PMID- 29172764
TI  - Policy Brief.

PMID- 29172765
TI  - Interdependent Career Types and Divergent Standpoints on the Use of Advanced
      Technology in Medicine.
AB  - This paper uses the case of the uneven use of a robotic technology to explain how
      physicians with similar training come to engage in different medical practices. I
      develop a conceptual framework in which their decisions to use advanced
      technologies are informed by "interdependent career types," a concept that
      incorporates features of the professional social context of physicians' work and
      the expertise they use, and reflects how medicine distributes expertise via
      formal and informal referral structures. I draw on data regarding specialized
      physicians' differentiated use of this technology over five years as well as
      interviews with those who continue to use the technology and those who have
      abandoned it. I argue that interdependent career types stratify physicians'
      standpoints on multiple dimensions of medical work-including those related to
      their concerns about reputation, inclinations toward risk, and preferences
      regarding the use of their bodies.

PMID- 29172766
TI  - Black Deaths Matter: Race, Relationship Loss, and Effects on Survivors.
AB  - Close relationships are a resource for mental and physical health that, like
      other social resources, is unequally distributed in the population. This article
      focuses on racial disparities in the loss of relationships across the life
      course. Racial disparities in life expectancy in the United States mean that
      black Americans experience the deaths of more friends and family members than do
      white Americans from childhood through later life. I argue that these losses are
      a unique type of stress and adversity that, through interconnected
      biopsychosocial pathways, contribute to disadvantage in health over the life
      course. I focus particularly on how the interconnected pathways associated with
      loss undermine opportunities for and increase risks to social ties throughout
      life, adding to disadvantage in health. I call on social scientists and policy
      makers to draw greater attention to this unique source of disadvantage for black
      children, adults, and families.

PMID- 29172767
TI  - Contesting and Differentially Constructing Uncertainty: Negotiations of
      Contraceptive Use in the Clinical Encounter.
AB  - Most women of reproductive age have access to highly effective contraception, and
      all available methods are associated with side effects. Whether a woman will
      experience side effects is uncertain, however, which can pose challenges for
      clinicians who discuss the methods with patients. In this study, we analyze 102
      contraceptive counseling visits to understand how clinicians discursively
      construct knowledge in the context of uncertainty. We find that while some
      present the uncertainty of side effects in a straightforward, patient-accessible
      way, others negotiate their predictions by (1) differentially constructing
      uncertainty, suggesting that positive side effects are likely and negative side
      effects are unlikely, and (2) contesting uncertainty, presenting the risk of
      serious side effects as controllable. In the end, these strategies deemphasize
      consideration of negative side effects in women's contraceptive decision making.
      Our results demonstrate the importance of elucidating the translation,
      instantiation, and construction of medical uncertainty both in theory and in
      practice.

PMID- 29172768
TI  - Planning for Future Care and the End of Life: A Qualitative Analysis of Gay,
      Lesbian, and Heterosexual Couples.
AB  - Two key components of end-of-life planning are (1) informal discussions about
      future care and other end-of-life preferences and (2) formal planning via living
      wills and other legal documents. We leverage previous work on the institutional
      aspects of marriage and on sexual-minority discrimination to theorize why and how
      heterosexual, gay, and lesbian married couples engage in informal and formal end
      of-life planning. We analyze qualitative dyadic in-depth interviews with 45
      midlife gay, lesbian, and heterosexual married couples ( N = 90 spouses).
      Findings suggest that same-sex spouses devote considerable attention to informal
      planning conversations and formal end-of-life plans, while heterosexual spouses
      report minimal formal or informal planning. The primary reasons same-sex spouses
      give for making end-of-life preparations are related to the absence of legal
      protections and concerns about discrimination from families. These findings raise
      questions about future end-of-life planning for same- and different-sex couples
      given a rapidly shifting legal and social landscape.

PMID- 29172769
TI  - Health Lifestyles in Adolescence and Self-rated Health into Adulthood.
AB  - Do health behaviors cluster together as health lifestyles in adolescence? Are
      these lifestyles socially patterned? Do these lifestyles impact physical health
      into adulthood? To answer these questions, we employed data from Waves 1 and 4 of
      the National Longitudinal Study of Adolescent to Adult Health ( n = 7,827). Our
      latent class analysis revealed four health lifestyles: (a) low risk, (b) moderate
      risk with substance use, (c) moderate risk with inactivity, and (d) high risk. As
      suggested by health lifestyle theory, membership in these classes varied
      according to gender, race-ethnicity, and family structure. Consistent with the
      life course perspective, regression analyses indicated that those in the high
      risk lifestyle tend to exhibit worse health in adolescence and adulthood than
      those in the low-risk lifestyle. Our findings confirm that socially patterned
      lifestyles can be observed in adolescence, and these lifestyles are potentially
      important for understanding the distribution of physical health across the early
      life course.

PMID- 29172772
TI  - Editorial Acknowledgment of Ad Hoc Reviewers.

PMID- 29172770
TI  - Couple-level Minority Stress: An Examination of Same-sex Couples' Unique
      Experiences.
AB  - Social stress resulting from stigma, prejudice, and discrimination-"minority
      stress"-negatively impacts sexual minority individuals' health and relational
      well-being. The present study examined how being in a same-sex couple can result
      in exposure to unique minority stressors not accounted for at the individual
      level. Relationship timeline interviews were conducted with 120 same-sex couples
      equally distributed across two study sites (Atlanta and San Francisco), gender
      (male and female), and relationship duration (at least six months but less than
      three years, at least three years but less than seven years, and seven or more
      years). Directed content analyses identified 17 unique couple-level minority
      stressors experienced within nine distinct social contexts. Analyses also
      revealed experiences of dyadic minority stress processes (stress discrepancies
      and stress contagion). These findings can be useful in future efforts to better
      understand and address the cumulative impact of minority stress on relational
      well-being and individual health.

PMID- 29172773
TI  - An update on liquid biopsy analysis for diagnostic and monitoring applications in
      non-small cell lung cancer.
AB  - INTRODUCTION: Collection of tumor samples is not always feasible in non-small
      cell lung cancer (NSCLC) patients, and circulating free DNA (cfDNA) extracted
      from blood represents a viable alternative. Different sensitive platforms have
      been developed for genetic cfDNA testing, some of which are already in clinical
      use. However, several difficulties remain, particularly the lack of
      standardization of these methodologies. Areas covered: Here, the authors present
      a review of the literature to update the applicability of cfDNA for diagnosis and
      monitoring of NSCLC patients. Expert commentary: Detection of somatic alterations
      in cfDNA is already in use in clinical practice and provides valuable information
      for patient management. Monitoring baseline alterations and emergence of
      resistance mutations is one of the most important clinical applications and can
      be used to non-invasively track disease evolution. Today, different technologies
      are available for cfDNA analysis, including whole-genome or exome sequencing and
      targeted methods that focus on a selection of genes of interest in a specific
      disease. In the case of Next Generation Sequencing (NGS) approaches, in depth
      coverage of candidate mutation loci can be achieved by selecting a limited number
      of targeted genes.

PMID- 29172774
TI  - Trenonacog alfa for prophylaxis, on-demand and perioperative management of
      hemophilia B.
AB  - INTRODUCTION: Current treatment for hemophilia B involves replacing the missing
      coagulation factor IX (FIX) with either plasma-derived or recombinant (r) FIX.
      Trenonacog alfa is the third normal half-life rFIX that has been granted FDA
      approval. Area covered: In this review, the authors examine trenonacog alfa for
      the treatment of hemophilia B including prophylaxis, on-demand and perioperative
      hemostasis. They compare the PK profile to nonacog alfa and evaluate the drug's
      efficacy and safety from published studies. Expert opinion: Trenonacog alfa
      appears to be an effective and safe treatment option for patients with hemophilia
      B with a PK profile similar to that of nonacog alfa. Despite the advent of
      extended half-life rFIX and other novel therapeutic approaches, normal half-life
      rFIX products, including trenonacog alfa, are likely to continue to have a place
      in hemophilia B treatment for at least the immediate future while the new
      landscape takes shape, particularly in countries that cannot afford the newer
      treatments.

PMID- 29172775
TI  - C/EBPbeta Promotion of MMP3-Dependent Tumor Cell Invasion and Association with
      Metastasis in Colorectal Cancer.
AB  - AIMS: Tumor metastasis is a significant obstacle to curing colorectal cancer
      (CRC). C/EBPbeta is thought to play an important role in CRC invasion and
      metastasis. In this study, we assessed whether C/EBPbeta-mediated tumor invasion
      was dependent on MMP3, the expression of which is upregulated by C/EBPbeta. We
      then determined whether C/EBPbeta upregulation was associated with MMP3 levels
      and metastatic status in human CRC patients. MATERIALS AND METHODS: A total of
      102 patients were recruited for this study. mRNA and protein levels of C/EBPbeta
      and MMP3 in CRC cell lines and patient specimens were determined by reverse
      transcription-polymerase chain reaction and western blot, respectively. Tumor
      cell invasion was analyzed using an in vitro Matrigel Invasion Assay. The
      correlation between C/EBPbeta and MMP3 expression was determined by Pearson's
      correlation analysis. RESULTS: Both mRNA and protein levels of MMP3 were
      upregulated by C/EBPbeta overexpression and downregulated by C/EBPbeta siRNA in
      HCT116 CRC cell cultures. C/EBPbeta-enhanced tumor cell invasion was inhibited by
      MMP3 siRNA. In human CRC patients, C/EBPbeta levels were correlated with MMP3
      levels and metastatic status. CONCLUSIONS: C/EBPbeta upregulation promoted tumor
      cell invasion in an MMP3-dependent manner in vitro and was associated with
      metastatic status in CRC.

PMID- 29172776
TI  - Self-efficacy in Activities of daily living and symptom management in people with
      dizziness: a focus group study.
AB  - BACKGROUND: Self-efficacy is associated with health status, health behaviour and
      health behaviour change in various chronic health conditions. PURPOSE: To
      describe self-efficacy in relation to Activities of daily living and symptom
      management in people with dizziness. MATERIAL AND METHODS: Thirteen women and
      three men, aged 45-82 years, with persistent dizziness (duration 4 months to 30
      years) were recruited from an outpatient physiotherapy unit. A qualitative study
      was conducted using four focus groups and one individual interview and was then
      analysed with qualitative content analysis. RESULTS: The participants conveyed,
      in-depth information concerning two predefined main categories. Self-efficacy in
      Activities of daily living was related to challenging body positions and motions,
      environments, social activities, work tasks, and complex cognitive behaviours.
      Self-efficacy in symptom management was related to distress and aggravated
      symptoms, unfamiliar environment, and unknown people. CONCLUSIONS: People with
      dizziness describe how self-efficacy for specific activities varies according to
      the perceived difficulty of the task, the context of the activity, and day-to-day
      variations in general wellbeing. The results underscore the importance of
      targeting self-efficacy in the rehabilitation of people with dizziness. Our
      findings can guide the rehabilitation process by providing a deeper understanding
      of self-efficacy judgements in relation to Activities of daily living and symptom
      management in people with dizziness. Implication for rehabilitation This study
      adds important in-depth knowledge to the rehabilitation area on self-efficacy
      beliefs in relation to Activities of daily living and symptom management in
      people with dizziness. Self-efficacy for specific activities varies according to
      the perceived difficulty of the task, the context in which the activity takes
      place and day-to-day variations in perceived general well-being. The results can
      be used as a topic list to guide rehabilitation efforts in exploring and
      intervening aspects of people's everyday activities that are affected by low self
      efficacy judgements. Activities perceived to be crucial to everyday life and
      important for well-being should be targeted in rehabilitation to increase self
      efficacy and thereby activity performance and participation in people with
      dizziness.

PMID- 29172777
TI  - A novel tumor-activated ALA fusion protein for specific inhibition on the growth
      and invasion of breast cancer cells MDA-MB-231.
AB  - OBJECTIVE: The aim of this research was to develop a novel ALA fusion protein for
      target to the malignant cells surface with high uPAR expression and locally
      release of the scorpion toxin AGAP in an uPA-cleavable manner. It will provide an
      effective approach for controlled release of the peptide toxins to treat
      cancerous cells. METHODS: The ALA fusion proteins were expressed in pichia
      pastoris, and the recombinant proteins were purified by Ni-NTA affinity
      chromatography. The proteins were added to human breast cancer cells (MDA-MB-231)
      and human embryonic kidney cells (HEK-293) in order to investigate the
      characteristic of selective targeting and releasing of scorpion toxin AGAP in
      cancer cells with high uPAR expression. The inhibitory effect of ALA on MDA-MB
      231, MCF7, LO2 and HEK-293 was evaluated by MTT assay. Moreover, the
      antiproliferation mechanism of ALA was determined by flow cytometric and western
      blot analysis. RESULTS: The results showed that ALA could target MDA-MB-231 cells
      and the scorpion toxin AGAP could be released with high efficiency and
      selectivity. ALA inhibited the growth and invasion of breast cancer cells MDA
      MB231. Also, cell apoptosis pathway was found to be associated with the
      inhibition mechanism of ALA according to the data of flow cytometric and western
      blot analysis. Therefore, ALA could be a novel antitumor candidate for targeting
      treatment of malignant cell. CONCLUSIONS: This study successfully demonstrated
      that fusion of biotoxins with tumor target domain could provide a simple yet
      effective way to delivery of peptide or protein drugs.

PMID- 29172778
TI  - Response to afatinib in treatment-naive patients with advanced mutant epidermal
      growth factor receptor lung adenocarcinoma with brain metastases.
AB  - BACKGROUND: Brain metastases are observable in 20-40% of non-small cell lung
      cancer patients, but standard treatments for such metastases may be intolerable
      to some. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) were found to be effective against mutant-EGFR lung adenocarcinomas, but
      data regarding their effectiveness, especially for the second-generation EGFR-TKI
      afatinib, is limited. This study compared key outcomes for afatanib monotherapy
      versus afatinib combined with whole-brain radiotherapy (WBRT) in treatment-naive
      lung adenocarcinoma patients harboring EGFR mutations. METHODS: A retrospective
      review of 28 brain metastatic lung adenocarcinoma patients treated between June
      2014 and December 2016 was conducted; 17 were treated with WBRT and maintenance
      afatinib therapy, while 11 received afatinib monotherapy. RESULTS: The patients
      were predominantly female (n = 17, 60.7%) and non-smokers (78.6%). Almost all the
      patients (89.3%) had an Eastern Cooperative Oncology Group performance status of
      0-2. The EGFR mutation type consisted of the del19 mutation in 57.1% of the
      patients (n = 16), while L858R mutations were found in 42.9% (n = 12). The mean
      number of brain metastases (6.1 +/- 5.0) was higher among the patients treated
      with afatinib monotherapy, while the mean size of the largest brain metastasis
      (19.0 +/- 10.5mm) was greater in the afatinib combined with WBRT group. The
      objective response rates for the afatinib monotherapy and combination therapy
      groups were 81.8% and 88.2%, respectively. However, the monotherapy group
      exhibited a significantly higher complete response rate for intracranial lesions
      (63.6% vs. 17.6%, p = 0.02), and there were no significant differences between
      the two treatment groups in overall survival or time to treatment failure.
      CONCLUSION: Afatinib can provide therapeutic efficacy and a good response rate in
      treatment-naive mutant-EGFR lung adenocarcinoma patients with brain metastases
      regardless of whether or not they also receive radiotherapy.

PMID- 29172779
TI  - The effect of magnesium sulfate on gene expression in maternal microvascular
      endothelial cells.
AB  - Preeclampsia is a severe complication of pregnancy associated with maternal and
      fetal morbidity and mortality. To date, magnesium sulfate remains the preferred
      method of treatment used to reduce the development of eclampsia. Our aim was to
      investigate the effects of magnesium sulfate on the expression of genes involved
      with endothelial function in maternal microvascular endothelial cells from both
      normal and preeclamptic pregnancies. Primary cells from normal pregnancies
      treated with 80 mg/L magnesium sulfate for 6 h revealed an overall trend of
      increased expression of angiogenic and vasopressor-related factors by qPCR
      analyses. Primary cells from preeclamptic pregnancies revealed an overall trend
      of decreased expression, with significantly lowered levels for vascular
      endothelial growth factor receptor 2, endothelin, and vascular cell adhesion
      protein-1. A comparison of treated cells revealed significantly increased levels
      for endoglin, vascular endothelial growth factor receptor 2, soluble fms-like
      tyrosine kinase-1, prostacyclin synthase, tumor necrosis factor alpha, tumor
      necrosis factor receptor 1, and endothelin in normal versus preeclamptic cells
      following treatment. These results reveal disparate activation of overall
      expression activity by magnesium sulfate in maternal endothelial cells from
      normal pregnancies over preeclamptic pregnancies.

PMID- 29172780
TI  - Understanding modern-day vaccines: what you need to know.
AB  - Vaccines are considered to be one of the greatest public health achievements of
      the last century. Depending on the biology of the infection, the disease to be
      prevented, and the targeted population, a vaccine may require the induction of
      different adaptive immune mechanisms to be effective. Understanding the basic
      concepts of different vaccines is therefore crucial to understand their mode of
      action, benefits, risks, and their potential real-life impact on protection. This
      review aims to provide healthcare professionals with background information about
      the main vaccine designs and concepts of protection in a simplified way to
      improve their knowledge and understanding, and increase their confidence in the
      science of vaccination ( Supplementary Material ). KEY MESSAGE Different vaccine
      designs, each with different advantages and limitations, can be applied for
      protection against a particular disease. Vaccines may contain live-attenuated
      pathogens, inactivated pathogens, or only parts of pathogens and may also contain
      adjuvants to stimulate the immune responses. This review explains the mode of
      action, benefits, risks and real-life impact of vaccines by highlighting key
      vaccine concepts. An improved knowledge and understanding of the main vaccine
      designs and concepts of protection will help support the appropriate use and
      expectations of vaccines, increase confidence in the science of vaccination, and
      help reduce vaccine hesitancy.

PMID- 29172781
TI  - Fracture risk assessment in postmenopausal women with diabetes: comparison
      between DeFRA and FRAX tools.
AB  - This study aimed to compare the performance of Fracture Risk Assessment Tool
      (FRAX) with that of Derived FRAX (DeFRA) in estimating fracture risk in a cohort
      of type-2 diabetes mellitus (T2DM) postmenopausal women. One hundred nineteen
      T2DM postmenopausal women and 118 consecutive healthy postmenopausal women were
      enrolled. Fracture risk was assessed with FRAX (adjusted or non- for trabecular
      bone score, TBS) and DeFRA. Bone mineral density (BMD) and TBS were evaluated by
      dual-energy X-ray absorptiometry (DXA). The outcome was the presence of
      vertebral/non-vertebral fragility fractures (FFs). T2DM women showed higher
      spinal BMD T-score (p < .05), but lower TBS (p < .05), than controls. Diabetic
      patients had higher prevalence of FFs compared to controls (p < .05), but no
      significant difference were found in the scores of any of the predictor tools.
      Differently, in the T2DM group, the scores of DeFRA, FRAX and adjusted-FRAX were
      significantly (p < .01 for all) higher in fractured compared with non-fractured
      women. DeFRA showed the best discriminative power among all fracture risk
      predictor tools (area under curves: DeFra: 0.89; adjusted FRAX: 0.80; non
      adjusted FRAX: 0.73). In summary, all fracture risk assessment tools appeared to
      be effective in predicting bone fractures in T2DM postmenopausal women, with
      DeFRA showing a slightly better diagnostic accuracy.

PMID- 29172782
TI  - Efficacy of Tribulus Terrestris for the treatment of premenopausal women with
      hypoactive sexual desire disorder: a randomized double-blinded, placebo
      controlled trial.
AB  - Although hypoactive sexual desire disorder (HSDD) is the most common sexual
      complaint, there is no consensus for the ideal treatment. Our study aimed to
      evaluate the efficacy of treating premenopausal women with HSDD with Tribulus
      terrestris and its effect on the serum levels of testosterone. We performed a
      prospective, randomized, double-blind, placebo-controlled trial, with 40
      premenopausal women reporting diminished libido, receiving T. terrestris or
      placebo. The questionnaires FSFI and the QS-F were used to evaluate sexual
      dysfunction before and after treatment. Patients treated with T. terrestris
      experienced improvement in total score of FSFI (p < .001) and domains "desire" (p
      < .001), "sexual arousal" (p = .005), "lubrication" (p = .001), "orgasm" (p
      <.001), "pain" (p = .030) and "satisfaction" (p = .001). Treatment with placebo
      did not improve the scores for the "lubrication" and "pain". QS-F scores showed
      that patients using T. terrestris had improvements in "desire" (p = .012),
      "sexual arousal/lubrication" (p = .002), "pain" (p = .031), "orgasm" (p = .004)
      and "satisfaction" (p = .001). Women treated with placebo did not score
      improvements. Women receiving T. terrestris had increased levels of free (p =
      .046) and bioavailable (p < .048) testosterone. T. terrestris might be a safe
      alternative for the treatment of premenopausal women with HSDD as it was
      effective in reducing the symptoms, probably due to an increase in the serum
      levels of free and bioavailable testosterone.

PMID- 29172783
TI  - Assessment of the bioactive compounds, antioxidant and antibacterial activities
      of Isodon rubescens as affected by drying methods.
AB  - The influence of natural drying (ND), hot-air drying (HD), vacuum drying (VD),
      infrared drying (ID) and freeze drying (FD) on bioactive compounds and
      bioactivities of Isodon rubescens (Hemsl.) was investigated in this study. The
      results showed that different drying methods resulted in the differences in
      bioactive compositions' content, antioxidant and antibacterial activities of
      extracts from I. rubescens. FD sample possessed the highest content of total
      phenolics, total flavonoids and several main phenolic compounds, as well as the
      stronger antioxidant and antibacterial activities, followed by ND, HD and VD, the
      lowest for ID samples. For this reason, freeze drying would seem to be more
      advisable for the drying I. rubescens, and future studies could focus on the
      quality evaluation and optimising various drying parameters.

PMID- 29172784
TI  - Good agreement between echocardiography and impedance cardiography in the
      assessment of left ventricular performance in hypertensive patients.
AB  - BACKGROUND: Impedance cardiography (ICG) is a noninvasive hemodynamic monitoring
      tool which can define hypertensive patients' hemodynamic profiles and help to
      tailor antihypertensive therapy. This study assesses the concordance between ICG
      derived indexes used to evaluate left ventricular performance and transthoracic
      echocardiography (TTE) in hypertensive patients. METHODS: In this IMPEDDANS post
      hoc analysis, the ICG-derived indexes are compared with TTE by Bland-Altman
      method. Statistical significance of the relationship between the values obtained
      was assessed by generalized linear mixed-effects models. RESULTS: In supine
      position, Bland-Altman analysis showed good concordance for cardiac output (CO)
      (mean difference of 0.006 mL/min [-0.120; 0.133]), cardiac index (CI) (mean
      difference of 0.016 mL/min/m2 [-0.471; 0.504]), pre-ejection period (PEP) (mean
      difference of -0.216 ms [-4.510; 4.077]), left ventricular ejection time (LVET)
      (mean difference of -0.140 ms [-6.573; 6.293]), and systolic time ratio (STR)
      (mean difference of -0.00004 [-0.008; 0.008]). In orthostatic position, good
      concordance was found for CO (mean difference 0.028 mL/min [-2.036; 1.980]), CI
      (mean difference -0.012 mL/min/m2 [-1.063; 1.039]), and STR (mean difference 
      0.101 [0.296; 0.094]). No significant difference between methods was identified
      by the linear mixed-effects models. CONCLUSION: The ICG-derived indexes CO, CI,
      PEP, LVET, and STR in supine position have good agreement with TTE. Therefore,
      ICG can be used to accurately evaluate left ventricular performance.

PMID- 29172785
TI  - Examining the noisy life of the college musician: weeklong noise dosimetry of
      music and non-music activities.
AB  - OBJECTIVE: To examine the contribution of all daily activities, including non
      music activities, to the overall noise exposure of college student musicians, and
      to compare their "noise lives" with those of non-musician college students.
      DESIGN: Continuous week-long dosimetry measurements were collected on student
      musicians and non-musicians. During the measurement period, participants recorded
      their daily activities in journals. STUDY SAMPLE: 22 musicians and 40 non
      musicians, all students (aged 18-24 years) at the University of Connecticut.
      RESULTS: On every day of the week, musicians experienced significantly higher
      average exposure levels than did non-musicians. Nearly half (47%) of the
      musicians' days exceeded a daily dose of 100%, compared with 10% of the non
      musicians' days. When the exposure due to music activities was removed, musicians
      still led noisier lives, largely due to participation in noisier social
      activities. For some musicians, non-music activities contributed a larger share
      of their total weekly noise exposure than did their music activities.
      CONCLUSIONS: Compared with their non-musician peers, college student musicians
      are at higher risk for noise-induced hearing loss (NIHL). On a weekly basis, non
      music activities may pose a greater risk to some musicians than music activities.
      Thus, hearing health education for musicians should include information about the
      contribution of lifestyle factors outside of music to NIHL risk.

PMID- 29172787
TI  - Adverse perinatal outcomes associated with trial of labor after cesarean section
      at term in pregnancies complicated by maternal obesity.
AB  - INTRODUCTION: Obesity is associated with higher risks for intrapartum
      complications. Therefore, we sought to determine if trial of labor after cesarean
      section (TOLAC) will lead to higher maternal and neonatal complications compared
      to repeat cesarean section (RCD). METHODS: This was a retrospective cohort
      analysis of singleton nonanomalous births between 37 and 42 weeks GA complicated
      by maternal obesity (body mass index (BMI) >= 30 kg/m2) and history of one or two
      previous cesarean deliveries. Outcomes were compared between TOLAC and RCD. The
      maternal outcomes of interest included blood transfusion, uterine rupture,
      hysterectomy, and intensive care unit admission. Neonatal outcomes of interest
      included 5-minute Apgar score <7, prolonged assisted ventilation, neonatal
      intensive care unit admission, neonatal seizures, and neonatal death. RESULTS:
      There were 538,264 pregnancies included. Compared with RCD, TOLAC was associated
      with an absolute increase in the following neonatal outcomes: low 5-min Apgar
      score (0.6%, p < .001), neonatal intensive care unit (NICU) admission (0.8%, p <
      .001), neonatal seizure (0.1 per 1000 births, p = .037), and neonatal death (0.2
      per 1000 births, p = .028). Additionally, TOLAC was associated with an absolute
      increase in following maternal outcomes: blood transfusion (0.1%, p < .001),
      uterine rupture (0.18%, p < .001) and ICU admission (0.1%, p = .011).
      CONCLUSIONS: TOLAC among obesity pregnancies at term increases the risk of
      maternal and neonatal complications compared with RCD.

PMID- 29172786
TI  - The Relationship Between Plasma Concentrations of Lutein and Zeaxanthin with Self
      Reported and Actual Prevalence of AMD in an Irish Population-Based Sample.
AB  - PURPOSE: To investigate plasma lutein (L) and zeaxanthin (Z) concentrations with
      grading-confirmed and self-reported prevalence of age-related macular
      degeneration (AMD). MATERIAL AND METHODS: Data collected from a nationally
      representative prospective cohort study of community-dwelling adults aged 50
      years and over in the Republic of Ireland. Participants underwent a computer
      assisted personal interview and a center-based health assessment. Plasma
      concentrations of L and total Z (Z and meso-zeaxanthin [MZ]) were measured by
      high performance liquid chromatography, and retinal photographs were graded using
      a version of the AMD International Classification and Grading System. Consumption
      of supplements containing L and/or Z and/or MZ was recorded as supplement use.
      Four groups were identified: Group 1 (n = 24): AMD-afflicted and correctly aware;
      Group 2 (n = 264): AMD-afflicted but unaware; Group 3 (n = 41): AMD-free and
      incorrectly believed that they were afflicted with the condition; Group 4 (n =
      4094): AMD-free and correctly self-reported absence of AMD. RESULTS: Of 4,423
      participants with plasma concentrations of L and Z and gradable retinal
      photographs, 288 (6.5%) were afflicted with AMD, and 65 (1.5%) self-reported AMD.
      Controlling for family history and age, the relationship between grading
      confirmed AMD and plasma L was positive and significant (p < 0.001). Mean plasma
      concentrations of L in Group 2 (mean = 0.2162 +/- 0.132 umol) and Group 4 (mean =
      0.2040 +/- 0.121 umol/L) were significantly lower than Group 1 (mean = 0.4691 +/-
      0.0.372 umol/L) and Group 3 (mean = 0.3176 +/- 0.0.235 umol/L). Supplement use
      was reported by 41.7% and 17.1% of participants in Groups 1 and 3, respectively,
      but only 2.7% and 1.9% of participants in Groups 2 and 4, respectively.
      CONCLUSION: A belief that one suffers from AMD, whether justified or not, is
      associated with supplement use and with higher plasma concentrations of L.

PMID- 29172788
TI  - Estimation of salt intake and sodium-to-potassium ratios assessed by urinary
      excretion among Japanese elementary school children.
AB  - Dietary salt intake is largely responsible for the increase in blood pressure
      with age. It is important to start effective prevention approaches during
      childhood. In this study, we estimated salt intake and sodium-to-potassium (Na/K)
      ratios assessed by urinary excretion among elementary school children in Kyoto,
      Japan. A total of 331 subjects aged 9-11 years participated in school checkups in
      April 2015. Urinary concentrations of sodium, potassium, and creatinine were
      measured in first morning urine samples. The subjects' dietary habits were
      confirmed by questionnaires completed by their parents. The median estimated
      urinary sodium excretion was 129.0 mmol/day (5.7g/day of salt). In 30.2% of the
      subjects, their estimated salt intake exceeded their age-specific dietary goal
      for salt intake recommended by the Dietary Reference Intakes for Japanese 2015.
      Multivariate linear regression model analysis after adjustment for age revealed a
      significant positive correlation between seaweeds or fish paste products
      consumption and the estimated salt intake (p = 0.02 and 0.02, respectively). The
      median urinary Na/K ratio (mEq/mEq) was 4.5. Multivariate linear regression model
      analysis revealed a significant negative correlation between fruit consumption
      and urinary Na/K ratio (p = 0.04). These results suggest that the high sodium
      intake and the high Na/K ratios occur among Japanese elementary school children,
      and that the urinary Na/K ratio in children may be reduced by the daily
      consumption of fruit.

PMID- 29172789
TI  - Morphometric analysis of human oocytes using time lapse: does it predict embryo
      developmental outcomes?
AB  - The aim of this prospective study was to evaluate the relationship between
      morphometric parameters of metaphase II (MII) oocytes and the morphokinetic
      behaviour of subsequent embryos derived by intra-cytoplasmic sperm injection
      (ICSI). The association between oocyte morphometry: (whole oocyte), ooplasm,
      width of zona pellucida (ZP) and perivitelline space (PVS) and first polar body
      (PB) with embryo morphokinetic variables, including time of second PB extrusion
      (tPB2), pronuclei appearance (tPN), pronuclei fading (tPNf), formation of two to
      eight cells (t2 to t8) and irregular cleavage events [uneven at two cells stage,
      cell fusion (Fu) and trichomonas mitoses (TM)] were assessed. tPB2, t5 and t8
      timings were related to the ooplasm diameter (p = 0.003, r = -0.12; p = 0.001, r
      = -0.16; p < 0.001 r = -0.36, respectively); otherwise, there were no significant
      relationships apart from an association between the oocyte morphometry and other
      morphokinetic parameters, irregular cleavage embryos as well as embryo arrest
      which approached significance (p > 0.05). Overall, the data showed that
      morphometric parameters of oocytes did not provide a tool for the prediction of
      embryo morphokinetic or embryo selection in ICSI cycles. However, ooplasm
      diameter might be useful as a marker for predicting the timing of embryo
      cleavage.

PMID- 29172790
TI  - Detection and reaction thresholds for reverse alarms in noise with and without
      passive hearing protection.
AB  - OBJECTIVE: To measure masked detection and reaction thresholds for two reverse
      alarms (tonal and broadband) and compare results to available standards and
      psychoacoustic criteria for setting alarm levels. DESIGN: Alarm detection and
      reaction thresholds were adaptively measured in 80-dBA background noises without
      hearing protection (Experiment 1), and with a passive earmuff-style hearing
      protection device (HPD) (Experiment 2). STUDY SAMPLE: Twenty-four young adults
      with normal hearing in each experimental group. RESULTS: Reverse alarms remained
      audible at levels well-below background noises [thresholds: -11 to -25 dB signal
      to-noise ratio (SNR)], with and without the selected HPD. Detection was more
      influenced by alarm and noise type, while reaction was more susceptible to HPD
      use. HPD use resulted in lower detection thresholds by up to 2.5 dB compared to
      unprotected listening but increased reaction thresholds by 5-10 dB depending on
      the alarm. CONCLUSIONS: Since noise type appears to have a more limited effect on
      reaction thresholds, adjusting alarms based on a global dBA method appears
      preferable to methods based on masked detection thresholds. However, while the >0
      dB SNR recommended in ISO 9533 seems adequate for unprotected listening, an
      additional 5-10 dB may be warranted to elicit the same reaction when the selected
      HPD is used.

PMID- 29172791
TI  - Teaching interprofessional teamwork skills to health professional students: A
      scoping review.
AB  - An expanding body of literature is examining interprofessional teamwork and its
      effect in healthcare. To produce capable healthcare professionals prepared to
      participate in interprofessional roles, teamwork training must begin early in
      health professional students' training. The focus of this scoping review was to
      explore interprofessional education (IPE) studies designed to teach and/or assess
      interprofessional teamwork skills to students from two or more different health
      professions, to find and describe effective pedagogy and assessment strategies.
      Using a scoping review methodology, 1,106 abstracts were reviewed by three teams
      of investigators. Eligibility criteria were inclusion of students in
      interprofessional teams, an intervention to improve interprofessional teamwork
      skills and assessment of outcomes related to teamwork. Thirty-three studies met
      the criteria for inclusion. The literature was varied in terms of study design,
      teaching methods and assessment measures for interprofessional teamwork. The lack
      of rigorous, comparable studies in this area makes recommending one teaching
      method or assessment measure over another difficult. Regardless of teaching
      method, it appears that most learning activities where interprofessional teams
      interact result in positive changes in student perceptions and attitudes towards
      IPE and practice. As health education programs seek to incorporate more
      interprofessional activities into their respective programs, it is important to
      review methods and measures that would best fit their individual program. This
      review highlights the importance of standardising the reporting of methods and
      outcomes for those who wish to incorporate the studied methods into their
      curricula.

PMID- 29172792
TI  - Combination therapy for extensively-drug resistant gram-negative bacteria.
AB  - INTRODUCTION: The ongoing crisis and emergence of extensively-drug resistant
      (XDR) gram-negative pathogens in the nosocomial setting is worrisome. The limited
      armamentarium in combination with the increasing resistance rates of last resort
      antibiotics has led clinicians to re-exploit existing antibiotic classes. Areas
      covered: Current state of evidence concerning the administration of monotherapy
      versus combination therapy for the treatment of XDR gram-negative microorganism
      as well as salvage treatment are presented. Herein, the current knowledge
      concerning in vitro studies, animal models and clinical studies are discussed in
      detail. Expert commentary: The efficacy of combination therapy in carbapenemase
      producing K. pneumoniae is associated with reduced mortality in patients with
      septic shock and rapidly fatal underlying diseases. There is moderate evidence in
      support of the use of monotherapy for treating carbapenemase-producing
      Acinetobacter baumannii infections, however for septic shock patients, cancer
      patients and infections with an isolate with MIC in the upper limit of
      susceptibility combination therapy could be recommended. There are currently
      minimal and of low quality clinical evidence suggesting that combination
      treatment has no therapeutic advantage over monotherapy for XDR Pseudomonas
      aeruginosa infections. The in vivo validity of novel compounds and necessity for
      combination therapy is to be evaluated in future studies particularly for XDR
      infections.

PMID- 29172793
TI  - Impact of obstructive sleep apnea on blood pressure and cardiovascular risk
      factors in Japanese men: A cross-sectional study in work-site group.
AB  - It has been shown that obstructive sleep apnea (OSA) is related to hypertension
      and cardiovascular disease; however, the prevalence of OSA in general population
      and the impact of it on blood pressure especially in Japan has not been well
      determined. We have conducted a screening test for OSA from 2003 to 2011. In
      addition, a cross-sectional analysis was performed in 2012 to determine the
      association of OSA and cardiovascular risk factors in Japanese men (18-69 years
      of age; mean age, 44.4 +/- 0.2). The study group consisted of 2208 male
      employees, and OSA was evaluated by using the 4% oxygen desaturation index and
      apnea-hypopnea index (AHI). The prevalence of mild-to-moderate (5<=AHI<30) and
      severe (AHI>=30) OSA in the studied subjects were 7.1%, and 6.1%, respectively.
      Among the 135 severe OSA subjects, 105 (77.8%) had been treated with continuous
      positive airway pressure. Both systolic and diastolic blood pressures (DBP) were
      significantly increased in the subjects with severe OSA compared with those
      without OSA. These associations in DBP remained observed after adjustment for
      age, body mass index (BMI), estimated glomerular filtration rate, HbA1c, current
      alcohol intake, current smoking habits, and OSA treatment. DBP in severe OSA
      subjects were significantly increased in 1807 subjects who were not treated for
      hypertension or OSA. However, the levels of blood pressures were not decreased by
      OSA treatment. These results suggest that the prevalence of OSA is relatively
      high in middle-aged Japanese men and that blood pressures were elevated in the
      subjects with severe OSA.

PMID- 29172794
TI  - Mortality in patients with atrial fibrillation and common co-morbidities - a
      cohort study in primary care.
AB  - OBJECTIVE: To study the association between cardiovascular co-morbidities and
      mortality risk in primary care patients with atrial fibrillation. METHODS: The
      study population included all adults (n = 12,283) >= 45 years diagnosed with AF
      at 75 primary care centres in Sweden between 2001 and 2007. The outcome was
      mortality (until 2010) and data were explored for co-morbidities using Cox
      regression with hazard ratios (HRs). Analyses were performed stratified by sex
      and by age-group (45-64, 65-74 and >=75 years of age) with adjustment for age,
      socio-economic factors and relevant co-morbidities. RESULTS: During a mean of 5.8
      years (standard deviation 2.4) of follow-up, 3954 (32%) patients died (1971 (35%)
      women, and 1983 (30%) men). High HRs were found for congestive heart disease
      (CHF) and cerebrovascular diseases for all age-groups among men and women (except
      for the 45-64 year old women); for coronary heart disease among the oldest men;
      for diabetes among the 65-74 year old men and the 45-64 year old women. Low HRs
      were found for hypertension among women >=75 years of age. CONCLUSIONS: In this
      clinical setting, CHF and cerebrovascular diseases were consistently associated
      with mortality in all age-groups. The possible protective effect by hypertension
      among elderly women should be interpreted with caution. KEY MESSAGES We found
      congestive heart failure and cerebrovascular diseases to be consistently
      associated with mortality in both women and men. We found hypertension to be
      associated with lower mortality risk among women >=75 years of age, although this
      finding must be interpreted with caution. Depression was found to be associated
      with increased mortality risk among men and women aged 65-74 years of age.

PMID- 29172795
TI  - From good to excellent: Improving clinical departments' learning climate in
      residency training.
AB  - INTRODUCTION: The improvement of clinical departments' learning climate is
      central to achieving high-quality residency training and patient care. However,
      improving the learning climate can be challenging given its complexity as a multi
      dimensional construct. Distinct representations of the dimensions might create
      different learning climate groups across departments and may require varying
      efforts to achieve improvement. Therefore, this study investigated: (1) whether
      distinct learning climate groups could be identified and (2) whether contextual
      factors could explain variation in departments' learning climate performance.
      METHODS: This study included departments that used the Dutch Residency
      Educational Climate Test (D-RECT) through a web-based system in 2014-2015. Latent
      profile analysis was used to identify learning climate groups and multilevel
      modeling to predict clinical departments' learning climate performance. RESULTS:
      The study included 1730 resident evaluations. Departments were classified into
      one of the four learning climate groups: substandard, adequate, good and
      excellent performers. The teaching status of the hospital, departments' average
      teaching performance and percentage of time spent on educational activities by
      faculty-predicted departments' learning climate performance. DISCUSSION: Clinical
      departments can be successfully classified into informative learning climate
      groups. Ideally, given informative climate grouping with potential for cross
      learning, the departments could embark on targeted performance improvement.

PMID- 29172796
TI  - Effect of orlistat or metformin in overweight and obese polycystic ovary syndrome
      patients with insulin resistance.
AB  - The aim of this study was to evaluate the effect of orlistat or metformin
      combined with Diane-35 on anthropometric, hormonal and metabolic parameters in
      overweight and obese polycystic ovary syndrome (PCOS) patients with insulin
      resistance (fasting insulin > 10 mIU/L). A total of 240 PCOS women were randomly
      allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group),
      orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body
      weight, BMI, waist and hip circumference, blood pressure, endocrine profile,
      lipid profile and insulin resistance were assessed at baseline and after 3
      months. Significant reductions in waist and hip circumference, serum LH, total
      testosterone and uric acid were observed in all groups compared with baseline. TG
      and TC significantly decreased in the OD group. Homeostasis model assessment
      insulin resistance (HOMA-IR) index was reduced in the OD (p = .015), MD (p =
      .001) and OMD (p = .004) groups. Body weight, BMI, systolic BP and HDL-C
      significantly changed in the OD and OMD group compared with the D group (p <
      .05). Side effects were less with orlistat than metformin. This study
      demonstrated that orlistat is more effective in reducing weight and lipid profile
      than metformin. Besides, orlistat has mild side-effects and is better tolerated
      compared with metformin.

PMID- 29172797
TI  - Infertility providers' and patients' views and experiences concerning doctor
      shopping in the USA.
AB  - Many questions arise concerning how infertility patients decide whether, how much
      and why or why not to consult more than one doctor and change physicians. To
      explore this issue, a total of 37 US in vitro fertilization (IVF) providers and
      patients were interviewed in-depth. Many infertility patients feel disappointed
      with infertility providers, especially after treatment failure, and then struggle
      to evaluate and weigh relative 'bedside manner' against technical skills,
      finances and hope, facing dilemmas of which doctor to choose, whether and how
      much, to 'shop around', how to do so, and whether and how much to give doctors
      'second chances'. Complex, dynamic processes can ensue: shopping for initial or
      subsequent physicians and consulting and/or changing doctors multiple times,
      based on differing treatment approaches. Patients may alter perceptions of
      physicians over time. Providers are often busy and have difficulty addressing
      patients' emotional stresses; and may provide providing 'false hope', and/or
      criticize colleagues' approaches. These data, the first to explore how
      infertility patients decide whether, how and why to consult with more than one
      infertility doctor, suggest that patients may 'doctor shop,', engaging in dynamic
      processes, wrestling to weigh communication vs. other skills. These data have
      important implications for future practice, research, guidelines and education.

PMID- 29172798
TI  - Physiology of blood pressure relevant to managing hypertension in pregnancy.
AB  - PURPOSE: Pregnancy causes physiological changes in maternal organ systems, and
      blood pressure (BP) is one of the variables affected. This review is focusing on
      the physiology of BP relevant to the management of hypertension in pregnancy.
      MATERIALS AND METHODS: A detailed literature search was performed using
      electronic databases (including WorldCat, PubMed, MEDLINE, Google Scholar) to
      retrieve and review reports related to physiology of BP in pregnancy. RESULTS:
      During pregnancy, there is vasodilation caused by mediators such as increased
      levels of progesterone and nitric oxide. The vasodilation leads to a reduction in
      vascular resistance, BP, and renal blood flow. In compensation, the following
      postulated events occur: activation of renin-angiotensin-aldosterone axis,
      resetting of osmotic threshold for thirst, and an increase in the production of
      vasopressin. Sodium and water conservation ensue to increase the total body
      water, end-diastolic volume, cardiac output, and BP. The increase in cardiac
      output incompletely compensates for the decreased vascular resistance, and BP
      therefore decreases in midpregnancy and returns to prepregnancy level toward
      term. CONCLUSIONS: An understanding of the physiological changes in BP is
      essential for appropriate management of pregnancy-related hypertension.

PMID- 29172799
TI  - Prognostic significance of downregulated BMAL1 and upregulated Ki-67 proteins in
      nasopharyngeal carcinoma.
AB  - This study assessed the prognostic value of BMAL1 and Ki-67 expression in
      patients with nasopharyngeal carcinoma. Level of BMAL1 mRNA was assessed in
      tissue specimens from 36 nasopharyngeal carcinomas and 20 nasopharyngeal chronic
      inflammations using quantitative reverse transcriptase-polymerase chain reaction.
      Expression of BMAL1 and Ki-67 proteins was analyzed immunohistochemically in 90
      paired nasopharyngeal carcinoma and distant normal tissues. The Kaplan-Meier
      curves and the Log-rank test were used to calculate prognostic significance
      stratified by BMAL1 and Ki67 protein expression and the COX regression model was
      to analyze the multivariate prognosis. BMAL1 mRNA was significantly reduced in
      nasopharyngeal carcinoma (4.67 +/- 0.27 versus 6.64 +/- 0.51 in chronic
      inflammation tissues, p = 0.002). Level of BMAL1 mRNA was associated with tumor
      distant metastasis (3.37 +/- 0.66 versus 5.04 +/- 0.27 compared with non
      metastasis, p = 0.011). Level of BMAL1 protein was also reduced in tumor tissues
      and BMAL1 expression was associated with better 1-, 3- and 5-year overall
      survival (OS) of cancer patients (92.6%, 69.2% and 62.3% versus 59.1%, 40.9% and
      0% in patients with low BMAL1 expressed tumors; p = 0.000). BMAL1 expression and
      age were independent prognostic factors for OS (p = 0.032). Furthermore, Ki-67
      expression was high in tumor versus normal tissues and associated with poor OS of
      cancer patients (p = 0.035). The Pearson correlation analysis showed that there
      was an inverse association between BMAL1 and Ki-67 protein expression (p =
      0.021). This study demonstrated that lost BMAL1 and Ki-67 overexpression were
      associated with poor OS of nasopharyngeal carcinoma patients.

PMID- 29172800
TI  - The acceptability and effectiveness of a questionnaire for the identification of
      risk factors for HIV and hepatitis B and C: An observational study in general
      practice.
AB  - BACKGROUND: Many people in Europe remain undiagnosed for human immunodeficiency
      virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV). OBJECTIVES: To
      evaluate acceptability and effectiveness of a questionnaire designed to
      facilitate identification of risk factors for these viruses. METHODS: We
      performed an observational study, in a prospectively enrolled cohort of patients
      in Paris (France) seen in 2014. Eighteen GPs administered a questionnaire to the
      first 50 patients, collecting information about risk factors. GPs were randomized
      into two groups: A (self-administered questionnaire) and B (GP-administered
      questionnaire). We used the overall response rate to assess the acceptability of
      the questionnaire. We used the rate of newly identified risk factors and compared
      the number of tests performed one year before and immediately after the
      intervention to assess the effectiveness of the questionnaire. RESULTS: 842
      patients were randomized: 349 (41.5%) in group A and 493 (58.5%) in group B.
      Acceptability was 88.5% (95%CI: 86.3-90.6); 93.1% (95%CI: 90.5-95.8) in-group A
      and 85.2% (95%CI: 82.1-88.3) in group B (P = 0.0004). Prevalence of risk factors
      was 51.8% (95%CI: 48.2-54.4) and 58.3% were newly identified (95%CI: 52.9-63.7).
      The number of HIV tests performed during the four weeks after intervention
      increased by 27% compared to the same period one year before (P = 0.22). It
      increased by 113% (P = 0.005) and 135% (P = 0.005) for HBV and HCV, respectively.
      CONCLUSION: The questionnaire proved acceptable and effective in identifying risk
      factors for HIV, HBV and HCV in general practice.

PMID- 29172801
TI  - The new European guideline on cardiovascular disease prevention; how to make
      progress in general practice?
AB  - The new guideline on cardiovascular disease (CVD) prevention, issued by the
      European Society of Cardiology was endorsed by 10 other societies, including
      Wonca Europe. It advices on how to reduce the cardiovascular (CV) risk in the
      population and attributes an important role to the general practitioner (GP). The
      GP is involved in treatment of the high-risk population as well as in public
      health measures to encourage a healthy lifestyle and CV risk factor reduction in
      the whole population. The new guideline gives room for a personalized approach
      and emphasizes that CV risk estimation and counselling need regular follow-up. We
      highlight the recommendations that most caught our eye and comment on the
      challenges for general practice.

PMID- 29172802
TI  - The effect of antidepressant medications in the management of heart failure on
      outcomes: mortality, cardiovascular function and depression - a systematic
      review.
AB  - OBJECTIVE: Depression is associated with increased morbidity, mortality and
      hospital readmission in patients with heart failure (HF). This systematic review
      aimed to compile studies examining whether the use of antidepressants could
      improve outcome in patients with HF and concomitant depression. METHODS: The
      electronic libraries Embase, OVID MEDLINE(R) and PsychInfo were used to search
      the following terms 'heart failure' AND 'anti-depressants'; 'heart failure' AND
      'TCA' OR 'SSRI' OR 'SNRI'. The result of this database search was analysed to
      select papers that satisfied our inclusion criteria. RESULTS: Of the 180 papers
      found in the original database search, only three met the inclusion criteria. A
      further two papers were added from hand-searching through the references. Three
      of these papers are randomised controlled trials (RCT); the other two, cohort
      studies. All studies show that antidepressants are well tolerated in this group.
      There was no significant difference in depressive symptoms between the test and
      placebo. The cardiac outcomes of patients with HF are not improved by the use of
      antidepressants relative to placebo. CONCLUSIONS: Antidepressants are not
      associated with increased mortality rate as established in previous papers.
      However, there is inadequate evidence that the use of antidepressants effects
      significant improvement in depression or cardiac outcomes.

PMID- 29172803
TI  - High normal blood pressure in early pregnancy also contribute to early onset
      preeclampsia and severe preeclampsia.
AB  - OBJECTIVE: This study was to evaluate effects of high normal blood pressure
      (HNBP) in early pregnancy on total preeclampsia, early preeclampsia, and severe
      preeclampsia. METHODS: We conducted a multicenter, national representative
      retrospective cohort study. HNBP was defined as systolic blood pressure between
      130 and 140 mmHg or diastolic blood pressure between 85 and 90 mmHg. We used
      multivariable logistic regression to examine the associations of HNBP and the
      risks of above three types of preeclampsia. RESULTS: We included 58 054 women who
      were normotensive and nulliparous in early pregnancy. 4 809 (8.3%) fulfilled the
      definition of having HNBP, 16 682 (28.7%) were in normal blood pressure group,
      and 36 563 (63.0%) were in optimal blood pressure group. The incidence rates of
      total preeclampsia, early preeclampsia, and severe preeclampsia were 2.1% (1
      217), 0.8% (491), and 1.4% (814), respectively. Compared to having optimal blood
      pressure, women with HNBP had significantly higher odds of total preeclampsia
      (odds ratio (OR) = 4.028, 95% confidence interval (CI) 3.377, 4.804), severe
      preeclampsia (OR = 3.542, 95% CI 2.851, 4.400), and early preeclampsia (OR =
      8.163, 95% CI 6.219, 10.715). Our restricted cubic spline results supported the
      dose-response relationship between continuous blood pressure and the odds ratio
      of three types of preeclampsia. The fraction of early preeclampsia associated
      with prehypertension was 58.6%, which was higher than those of total preeclampsia
      (42.2%) or severe preeclampsia (40.5%). CONCLUSION: Women in early pregnancy with
      HNBP more likely develop total preeclampsia, early preeclampsia and severe
      preeclampsia, compared to those with optimal blood pressure. HNBP contribute more
      to early preeclampsia than severe preeclampsia. Our study provided robust
      epidemiological evidences for monitoring HNBP in early pregnancy to reduce the
      risks of preeclampsia.

PMID- 29172804
TI  - Postpartum maternal adipokines and infant weight for length at 1 year in women
      with gestational diabetes.
AB  - BACKGROUND: Maternal, cord blood and childhood adipokines have been associated
      with childhood obesity. We investigated whether postpartum maternal adipokines
      are associated with increased weight at 1 year of age in children of women with
      gestational diabetes (GDM). METHODS: Plasma leptin and adiponectin concentrations
      were measured in 160 women at approximately 12 weeks following pregnancy with GDM
      and compared with infant weight for length z-score at 1 year of age after
      adjustment for maternal and infant demographic variables. RESULTS: No association
      was demonstrated between maternal postpartum leptin and adiponectin
      concentrations and infant weight for length z-score at 1 year of age.

PMID- 29172805
TI  - Letter in response to "Levetiracetam in toxic seizures".

PMID- 29172806
TI  - Hostile Attribution Bias as a Mediator of the Relationships of Psychopathy and
      Narcissism With Aggression.
AB  - Hostile attribution bias (HAB), the tendency to perceive hostility in ambiguous
      situations, has been linked to aggressive outcomes, such as reactive aggression.
      HAB has been connected to personality types involving hostile beliefs and
      reactive aggression, including narcissism and psychopathy. Specifically,
      secondary psychopathy is associated with HAB and reactive aggression. Despite
      research and theory connecting these constructs, few studies have examined if HAB
      mediates the relationships among psychopathy, narcissism, and aggression. The
      current study explores this possible mediation in an urban college sample.
      Narcissism was associated with aggression but not hostile aggression or HAB.
      Reactive aggression and HAB were both associated with psychopathy, but there were
      no mediation relationships. The associations with aggression may be, therefore,
      due to underlying traits of secondary psychopathy rather than the hostile
      attributions to which the traits contribute; consequently, treatments focused on
      reducing aggressive responses by correcting interpretations of social situations
      may not be successful.

PMID- 29172807
TI  - Impact of coping strategies on perceived stress, depression, and cortisol
      profiles among gynecologic cancer patients.
AB  - We explored associations between problem-focused, emotional processing, and
      emotional expression coping strategies and markers of stress including perceived
      stress, depressive symptoms, and diurnal cortisol profiles among women with
      gynecologic cancer. Problem-focused coping was associated with less perceived
      stress, fewer depressive symptoms, and more rhythmic diurnal salivary cortisol
      profiles. Emotional processing was associated with lower perceived stress and
      fewer depressive symptoms. Emotional expression was associated with fewer
      depressive symptoms and elevated diurnal mean and evening cortisol levels.
      Results point to key differences in coping strategies. In this sample, only
      problem-focused coping was linked with adaptive differences in both psychological
      and physiological stress measures.

PMID- 29172808
TI  - A prospective study exploring the construct and predictive validity of the COM-B
      model for physical activity.
AB  - This study examined the constructs of capability, opportunity and motivation from
      the COM-B model and their influence on moderate-to-vigorous physical activity.
      Using a prospective survey design, 186 healthy adults completed measures
      representing the theoretical domains framework mapped to the COM-B, and moderate
      to-vigorous physical activity 1 week later. The main indicators for the COM
      constructs were 'habits' (Capability), 'subjective norms' (Opportunity) and
      'exercise self-identity' (Motivation). Motivation (77%) and moderate-to-vigorous
      physical activity (50%) were strongly predicted, with Capability and Motivation
      as key drivers of behaviour. Motivation was a strong mediator for Capability on
      behaviour. Future research should consider this approach for other populations
      and behaviours.

PMID- 29172809
TI  - Bridging the Gap: Racial concordance as a strategy to increase African American
      participation in breast cancer research.
AB  - Lack of African American females in breast cancer research has been receiving
      substantial attention. This study seeks to identify research perceptions and
      motivating factors needed to increase racial/ethnic minority participation in
      breast cancer research. A total of 57 African American women (Sigma = 47.8
      years), from Rhode Island and Texas, completed a questionnaire and focus group.
      While many participants were not breast cancer survivors, they reported knowledge
      of their racial group's risk for breast cancer. One major finding that could be
      seen as both a facilitator and barrier is racial concordance between participant
      and researcher. Cultural sensitivity and trust building is recommended to
      increase minority participation.

PMID- 29172810
TI  - Perceived social support and life satisfaction in drug addicts: Self-esteem and
      loneliness as mediators.
AB  - This study was designed to investigate the mediation effects of both self-esteem
      and loneliness on the relationship between social support and subjective well
      being in drug addicts. In all, 110 participants, all drug addicts from Guangdong
      Fangcun Brain Hospital, completed the questionnaire. Pearson's correlation
      analysis showed that perceived social support was positively related to self
      esteem and life satisfaction and was negatively correlated with loneliness in
      drug addicts. Structural equation modeling estimated by the Bootstrap method
      indicated that loneliness and self-esteem partially mediated the association
      between perceived social support and life satisfaction. These findings provided
      insights into the association between perceived social support and life
      satisfaction in drug addicts.

PMID- 29172811
TI  - Why do they do it? Assessing self-report physical activity behavior and quality
      of life in individuals with multiple sclerosis.
AB  - Physical activity has been shown to effectively aid multiple sclerosis symptom
      management; however, individuals with multiple sclerosis tend to be inactive
      physically. Developing effective, sustainable, physical activity interventions
      involves first understanding motivators for physical activity. Open-ended surveys
      exploring physical activity motivators were collected from 215 individuals with
      multiple sclerosis. Responses indicate that self-efficacy and internalized
      motivation derived from physical activity outcomes were motivators for physical
      activity, and physical activity was cited as increasing overall quality of life.
      Future physical activity interventions should incorporate methods for building
      self-efficacy for physical activity and focus on increasing awareness of the long
      term physical benefits derived from physical activity.

PMID- 29172812
TI  - Validation of 'reported concussion' within a national health survey.
AB  - SETTING: The Canadian Community Health Survey (CCHS) is a national cross
      sectional health survey, which has collected information on injuries serious
      enough to limit normal activity. OBJECTIVE: To assess the construct and
      discriminant validity of reporting 'concussion or other brain injury' in the CCHS
      as the respondents' most serious injury. METHODS: Construct validity was assessed
      by describing the injury profile. Discriminant validity was assessed by examining
      differences between those reporting concussion or other brain injury, and either:
      respondents not reporting brain injury (population control); or respondents
      reporting orthopaedic injuries (orthopaedic control). RESULTS: In total, 1,852 of
      the 682,455 eligible CCHS respondents (>=12 years) reported a concussion or other
      brain injury within the prior year, a population annual incidence of 0.29%. Those
      reporting concussion or other brain injury were younger and male (p < 0.001),
      with an injury acquired by falling (p < 0.001) or sport or physical exercise (p <
      0.001). Most (78.4%) who reported concussions or other brain injuries received
      medical attention from a health professional within 48 hours of their injury. The
      reported injury profiles appear to differ from the population controls and those
      reporting orthopaedic injuries. CONCLUSIONS: The report of 'concussion or other
      brain injury' in the CCHS may be a valid source of population-based traumatic
      brain injury epidemiological data.

PMID- 29172813
TI  - A critical scoping review of the connections between social mission and medical
      school admissions: BEME Guide No. 47.
AB  - BACKGROUND: Despite a growing focus on the social accountability of medical
      schools, there has been no substantive review of admissions related to the social
      mission of medical schools. This paper reports on a critical scoping review of
      the connections between social mission and medical school admissions. METHODS:
      Searches of seven bibliographic databases identified 1258 unique articles. After
      filtering for relevance, 71 articles were considered for final review. The
      results of the data extraction were synthesized using a combination of
      qualitative and quantitative techniques. RESULTS: Five reviewers conducted 149
      data extractions from 71 papers. Social missions tended to focus either on access
      and equity issues for applicants from underrepresented populations or on the
      career choices of medical graduates and how they meet particular social needs.
      The connection between social missions and admissions was often implied but
      rarely considered or evaluated directly. There was a notable absence of empirical
      evidence, with calls for reform or program descriptions far outweighing the
      number of papers based on empirical findings. CONCLUSIONS: Despite the move to
      social missions in medical education, there remains little direct connection
      between missions and admissions and little evidence reflecting the efficacy or
      impacts of making this connection.

PMID- 29172814
TI  - Social media and professional identity: Pitfalls and potential.
AB  - INTRODUCTION: Social media developments have completely changed how information
      is accessed and communicated. While great potential exists with these platforms,
      recent reports of online unprofessional behavior by doctors has threatened the
      medical professional identity; a matter of critical importance for clinicians and
      medical educators. This paper outlines a role for social media in facilitating
      support for clinicians and medical teachers; it will raise awareness of pitfalls
      and explain ethical and legal guidelines. METHODS: An analysis of inappropriate
      behaviors and conflicting attitudes regarding what is acceptable in online posts,
      including the inter-generational contrast in online presence and perceptions of
      where the boundaries lie. RESULTS AND DISCUSSION: Guidance documents are analyzed
      and potentially confusing and conflicting statements are identified and
      clarified. The authors believe that clinicians and medical students must follow
      ethical imperatives in both personal and professional spheres. CONCLUSIONS: It is
      essential that medical educational and professional bodies encourage clinicians
      to support one another and share information online while providing clear legal
      and ethical advice on maintaining standards and avoiding common pitfalls.
      Education on the responsible use of social media and associated risk awareness
      should be a priority for medical school curricula.

PMID- 29172815
TI  - 'Modelling a Secure-Base' for Women with Complex Needs: Attachment-Based
      Interventions Used by Perinatal and Infant Mental Health Clinicians.
AB  - Infant well-being is intrinsically linked to maternal physical and emotional well
      being. Internationally health services have implemented policies to identify
      women at risk of mental health problems and developed effective care pathways.
      The aim of this paper is to describe how perinatal and infant mental health
      clinicians perceive their role and the attachment-based interventions they use in
      their work. The study comes from a larger mixed methods study, which examined two
      specialist perinatal and infant mental health services in New South Wales
      (Australia). Two hundred and forty-four medical records were reviewed, and six
      perinatal and infant mental health clinicians participated in in-depth semi
      structured interviews. Data were analysed by content and thematic analysis. One
      overarching theme, modelling a secure base and three supporting themes, enhancing
      reflective capacity, enhancing emotional regulation and enhancing empathy emerged
      from the analysis. These findings demonstrate how perinatal and infant mental
      health clinicians use attachment theory to inform practice by modelling "holding"
      and being a secure-base for women. They also provide a clearer understanding of
      perinatal mental health practice and can be used to inform educational programs
      for multidisciplinary mental health professionals particularly those working with
      women and infants.

PMID- 29172816
TI  - CT findings are highly predictive for perforation in patients with diffuse large
      B-cell lymphoma involving the intestines.
AB  - Patients with diffuse large B-cell lymphoma (DLBCL) presenting with intestinal
      involvement are prone to develop perforation. Identification of those who are at
      high risk for this complication would enable a rational-based decision regarding
      preemptive surgery. Although computed tomography (CT) is widely used at
      diagnosis, data regarding its ability to predict intestinal perforation are
      scanty. We performed a retrospective single-center study, including all
      consecutive DLBCL patients presented with intestinal involvement, assessing
      predictors for perforation with an emphasis on CT-related parameters. Forty-nine
      patients were included, 43 (88%) underwent CT scan at diagnosis. Ten patients
      (20%) developed intestinal perforation. A univariate regression analysis found
      increased risk among patients with a concentric, transmural lesion, and a longer
      involved intestinal segment. In conclusion, CT scan results can define patients
      with DLBCL and intestinal involvement who are at risk for perforation, suggesting
      that a preemptive surgical resection should be considered in these cases.

PMID- 29172817
TI  - The efficacy of problem solving therapy to reduce post stroke emotional distress
      in younger (18-65) stroke survivors.
AB  - PURPOSE: To investigate the efficacy of problem solving therapy for reducing the
      emotional distress experienced by younger stroke survivors. METHOD: A non
      randomized waitlist controlled design was used to compare outcome measures for
      the treatment group and a waitlist control group at baseline and post
      waitlist/post-therapy. After the waitlist group received problem solving therapy
      an analysis was completed on the pooled outcome measures at baseline, post
      treatment, and three-month follow-up. RESULTS: Changes on outcome measures
      between baseline and post-treatment (n = 13) were not significantly different
      between the two groups, treatment (n = 13), and the waitlist control group (n =
      16) (between-subject design). The pooled data (n = 28) indicated that receiving
      problem solving therapy significantly reduced participants levels of depression
      and anxiety and increased quality of life levels from baseline to follow up
      (within-subject design), however, methodological limitations, such as the lack of
      a control group reduce the validity of this finding. CONCLUSION: The between
      subject results suggest that there was no significant difference between those
      that received problem solving therapy and a waitlist control group between
      baseline and post-waitlist/post-therapy. The within-subject design suggests that
      problem solving therapy may be beneficial for younger stroke survivors when they
      are given some time to learn and implement the skills into their day to day life.
      However, additional research with a control group is required to investigate this
      further. This study provides limited evidence for the provision of support groups
      for younger stroke survivors post stroke, however, it remains unclear about what
      type of support this should be. Implications for Rehabilitation Problem solving
      therapy is no more effective for reducing post stroke distress than a wait-list
      control group. Problem solving therapy may be perceived as helpful and enjoyable
      by younger stroke survivors. Younger stroke survivors may use the skills learnt
      from problem solving therapy to solve problems in their day to day lives. Younger
      stroke survivors may benefit from age appropriate psychological support; however,
      future research is needed to determine what type of support this should be.

PMID- 29172818
TI  - New pharmacotherapy for the treatment of glaucoma.
AB  - INTRODUCTION: Glaucoma is the second leading cause of blindness in the world and
      current pharmacotherapies for glaucoma have remained relatively unchanged (with
      the exception of fixed combinations of previously available medications) since
      the mid-1990s with the development of prostaglandin analogues. Now, with both new
      formulations and new classes of medications with novel mechanisms of action, the
      medical therapy of glaucoma may be heralding a new dawn in medical management.
      Areas covered: This review outlines new topical therapies for intraocular
      pressure (IOP) lowering treatment, in addition to new formulations, preservative
      free options, and advances in glaucoma medical therapy delivery. We performed a
      comprehensive search for published studies for glaucoma medical therapy using the
      electronic database PubMed. A manual search for each therapy or delivery system
      was also performed. Expert commentary: These advances in glaucoma therapy have
      the potential to overcome many barriers to glaucoma's medical care, particularly
      in terms of adherence. However, both time and research are needed to prove the
      relative efficacy and safety of these new pharmacotherapies and products, helping
      us decide their role in the treatment of elevated intraocular pressure. We are
      hopeful that these new developments in therapy may bring more options for
      glaucoma medical therapy.

PMID- 29172819
TI  - Arias-Stella Reaction With Signet Ring-Like Cell Histomorphology.
AB  - Cells with their nucleus pushed to the periphery in a crescent-like fashion by
      intracytoplasmic vacuole(s) are referred to as signet ring cells when the
      vacuole(s) contain mucin and signet ring-like cells when they are empty or
      contain a material other than mucin. Signet ring cells are commonly associated
      with adenocarcinomas. These cells are uncommon in the endometrium and have been
      found to be associated with both malignant and benign processes. We report the
      first case of signet ring-like cells within endometrial glands with Arias-Stella
      reaction.

PMID- 29172821
TI  - Risk of donor demise after laser therapy for twin-twin transfusion when
      complicated by growth discordance and abnormal umbilical artery Doppler findings.
AB  - OBJECTIVE: To investigate the natural course of abnormal umbilical artery Doppler
      (UAD) findings in donor fetuses after laser surgery and the prognostic
      significance of resolution, persistence, or new onset UAD abnormalities with and
      without the presence of preoperative growth discordance. STUDY DESIGN:
      Retrospective cohort study of all monochorionic-diamniotic multi-fetal gestations
      diagnosed with twin-twin transfusion syndrome (TTTS) undergoing laser surgery at
      a single large metropolitan referral center from 2010-2016. The estimated fetal
      weight was measured preoperatively and the UAD were measured both pre- and
      postoperatively (median = 8 days). Patients were grouped according to the
      presence of abnormal UAD with or without growth discordance pre- and
      postoperatively. Risk ratios (RR) were calculated for each group for risk of
      intrauterine fetal demise compared to the pre- and postoperative normal UAD
      groups as the referents. RESULTS: There were eighty-one women who met inclusion
      criteria throughout the study period. Forty-three (53.1%) patients had abnormal
      donor twin UAD preoperatively and 33 (40.7%) were diagnosed with growth
      discordance. However, 13 (44.8%) had normalization of the UAD postoperatively
      (median = 8 days) with a similar rate of donor fetal demise as the non-discordant
      preoperative normal UAD group (7.7% versus 10.3%, p = .79). Abnormal preoperative
      UAD was associated with an increased risk of donor demise (RR 3.6, CI 1.1-12.1),
      which was further elevated in the presence of growth discordance (RR 5.2, CI 1.7
      16.3). The greatest risk for donor demise was seen if the UAD remained abnormal
      postoperatively with concomitant growth discordance (RR 10.3, CI 2.5-41.6).
      CONCLUSIONS: Preoperative abnormal donor UAD is a significant risk for donor
      demise post-laser therapy for TTTS. Persistent postoperative abnormal UAD with
      concomitant growth discordance confers the greatest risk for donor demise.
      However, resolution of abnormal UAD has a similar rate of donor demise when
      compared to patients with normal UAD preoperatively.

PMID- 29172820
TI  - A Sclerosing Perineurioma With Collagen Rosette Formation: Benign Mimic of Low
      Grade Fibromyxoid Sarcoma.
AB  - We report the case of a sclerosing perineurioma with conspicious collagen rosette
      formation in a 20-year-old male presenting with a firm, painless nodule on the
      palmar side of his right ring finger. The main differential diagnosis is a low
      grade fibromyxoid sarcoma. The distinction between these entities is important
      because low-grade fibromyxoid sarcoma has a metastatic potential, while, as a
      rule, perineuriomas are benign. The presence of collagen rosettes in this current
      case makes this distinction even more difficult given that approximately 30% of
      low-grade fibromyxoid sarcoma cases show the focal presence of collagen rosettes.
      The demonstration of the characteristic t(7;16), t(11;16) or t(11;22)
      translocations (resulting in the FUS-CREB3L2, FUS-CREB3L1 or EWSR1-CREB3L1 fusion
      genes, respectively) or immunoreactivity for MUC4, a recently described sensitive
      and specific marker for low-grade fibromyxoid sarcoma, remain the gold standard
      in the diagnosis of low-grade fibromyxoid sarcoma, differentiating it from
      perineurioma. This case is, to our knowledge, the first report on collagen
      rosettes in sclerosing perineurioma, extremely well mimicking low-grade
      fibromyxoid sarcoma, and further expanding the morphological spectrum of this
      rare subtype of perineurioma.

PMID- 29172822
TI  - Antithrombotic efficacy of bivalirudin compared to unfractionated heparin during
      percutaneous coronary intervention for acute coronary syndrome.
AB  - Bivalirudin is associated with an increased risk of acute stent thrombosis (AST)
      compared to unfractionated heparin (UFH) in acute coronary syndrome patients
      (ACS) during short-duration percutaneous coronary intervention (PCI). The
      mechanisms involved are unknown. We aimed to investigate the antithrombotic
      efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we
      prospectively enrolled 30 patients undergoing PCI for a non-ST elevation ACS.
      They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg)
      or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion
      during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at
      the time of PCI. The VASP index and activated partial thromboplastin time (aPTT)
      were used to assess the course of platelet reactivity (PR) and antithrombotic
      activity. The two groups were similar regarding baseline, angiographic, and
      interventional characteristics. There was no difference between the two groups in
      the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4
      h after the LD of ticagrelor. The level of antithrombotic activity was
      significantly lower in the bivalirudin group compared to the UFH group (p <
      0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS
      undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is
      significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to
      the excess in thrombotic acute events observed during short-duration PCI.

PMID- 29172823
TI  - Eye-tracking technology in medical education: A systematic review.
AB  - BACKGROUND: Eye-tracking technology is an established research tool within allied
      industries such as advertising, psychology and aerospace. This review aims to
      consolidate literature describing the evidence for use of eye-tracking as an
      adjunct to traditional teaching methods in medical education. METHODS: A
      systematic literature review was conducted in line with STORIES guidelines. A
      search of EMBASE, OVID MEDLINE, PsycINFO, TRIP database, and Science Direct was
      conducted until January 2017. Studies describing the use of eye-tracking in the
      training, assessment, and feedback of clinicians were included in the review.
      RESULTS: Thirty-three studies were included in the final qualitative synthesis.
      Three studies were based on the use of gaze training, three studies on the
      changes in gaze behavior during the learning curve, 17 studies on clinical
      assessment and six studies focused on the use of eye-tracking methodology as a
      feedback tool. The studies demonstrated feasibility and validity in the use of
      eye-tracking as a training and assessment method. CONCLUSIONS: Overall, eye
      tracking methodology has contributed significantly to the training, assessment,
      and feedback practices used in the clinical setting. The technology provides
      reliable quantitative data, which can be interpreted to give an indication of
      clinical skill, provide training solutions and aid in feedback and reflection.
      This review provides a detailed summary of evidence relating to eye-tracking
      methodology and its uses as a training method, changes in visual gaze behavior
      during the learning curve, eye-tracking methodology for proficiency assessment
      and its uses as a feedback tool.

PMID- 29172824
TI  - Aliskiren and valsartan in combination is a promising therapy for hypertensive
      renal injury in rats.
AB  - : Neither ACEI nor ARBs completely repress the RAAS. Aliskiren is a newer agent
      that inhibits renin. However, it increases the biosynthesis and secretion of
      renin and prorenin, that might induce renal tissue damage. This study was
      conducted to investigate the renoprotective effects of aliskiren and valsartan
      the ARB, either alone or in combination, on hypertensive nephropathy induced by L
      NAME. Aliskiren (50 mg/kg/daily i.p.), valsartan (10 mg/kg daily i.p.) alone or
      in half dose combination were administered with L-NAME (30-40 mg daily in
      drinking water) for 8 weeks. Aliskiren and valsartan significantly reduced
      systolic blood pressure, proteinuria, serum creatinine, blood urea nitrogen,
      oxidative stress, and structural renal injury although not to the same extent.
      Valsartan reduced systolic blood pressure and proteinuria in L-NAME treated rats
      more significantly than aliskiren. However, glomerular collapse index and the
      expansion of interstitial tissue were significantly attenuated by aliskiren than
      by valsartan. Cotreatment with aliskiren and valsartan markedly reduced the
      oxidative stress and further reduced the glomerular collapse and the expansion of
      interstitial tissue compared with aliskiren monotherapy. CONCLUSION: These
      results suggest that therapies aimed at different targets within the RAAS may
      have additional effects in attenuating structural injury in experimental
      hypertensive nephropathy.

PMID- 29172826
TI  - Testing Nursing Sensitive Outcomes in Out-Patient Drug Addicts, with "Nursing
      Role Effectiveness Model".
AB  - Our aim was to identify factors that contribute to a better outcome in drug users
      and to understand the effectiveness of nursing interventions, by applying
      "Nursing Role Effectiveness Model" (NREM). It's a correlational, cross-sectional
      study with 180 drug users in a methadone program, randomly selected from three
      community services. We identified that treatment time, lower co-morbidities, less
      poly-drug use, family support and being employed contribute to a better quality
      of life, better mental health, less substance addiction consequences and more
      satisfaction with nursing care (p < 0.05). Those data were also related with
      nursing interventions using Structural Equation Model and we found that nursing
      care contributes 29% to health outcome improvement. The model revealed itself
      adequate to assess the effectiveness of nursing interventions (X2: 82.51/(34) =
      2.426; p < 0.01, NFI = 0.927, CFI = 0.955, RFI = 0.903, GFI = 0.917, PGFI =
      0.567, PCFI = 0.722, PNFI = 0.700, RMSEA = 0.089). Compared with the NREM
      original model, our findings reveal new relationships between the users'
      structural variables and the health outcomes and also relationship between units'
      structural variables and nurses' structural variables.

PMID- 29172825
TI  - Metal load assessment in patient pulmonary lavages: towards a comprehensive
      mineralogical analysis including the nano-sized fraction.
AB  - Mineralogical analyses of clinical samples have been proved useful to identify
      causal relationship between exposure to airborne particles and pulmonary
      diseases. The most striking example is asbestosis where the assessment of
      asbestos bodies in patient lung samples has allowed defining values specific of
      pathologies. However, this type of analyses only considers the micro-sized
      fraction of the particles, neglecting the specific impact of nano-sized particles
      which have been otherwise shown to be reactive and able to induce biological
      effects. Similarly, in nanotoxicology, the mineralogical analysis of pulmonary
      fluids could be used as an indicator of exposure to inhaled nanoparticles and
      could help investigations on the relationship between exposure to these
      nanoparticles and lung diseases. We designed this study first to demonstrate the
      technical feasibility of this approach, then to get a clear picture of the metals
      present, and in what form, in patient lungs and finally to determine if indeed it
      is worth investigating separately the micro, sub-micro and nano fractions.
      Broncho-alveolar lavages were recovered from 100 patients suffering from
      interstitial lung diseases. A protocol was specifically developed to isolate
      three fractions containing respectively microparticles, sub-microparticles and
      nanoparticles with ions. The metal content in each fraction was qualitatively and
      quantitatively characterized. Results showed significant differences between the
      three fractions in terms of metal load confirming that the separate analysis of
      the fractions is relevant. It also means that the assessment of the micro-sized
      fraction alone, as commonly done in clinical practice, only gives a partial view
      of the mineralogical analysis.

PMID- 29172827
TI  - The prevalence of congenital malformations is still higher in pregnant women with
      pregestational diabetes despite near-normal HbA1c: a literature review.
AB  - AIMS/HYPOTHESIS: We assessed the association between congenital malformations and
      maternal hyperglycemia in pregnant women with pregestational (type 1 or type 2)
      diabetes and investigated if the rate of congenital malformations was similar in
      women with near-normal glycemic control compared to the background population. We
      also assessed the association between congenital malformations and maternal
      hyperglycemia in pregnant women with pregestational diabetes with special focus
      on women with near-normal HbA1c in early pregnancy. MATERIALS AND METHODS: This
      is a literature review based on an electronic literature search of the databases
      PubMed, Cochrane, Embase and Web of Science conducted in July 2017 using the
      search terms diabetes, pregnancy, HbA1c or glycemic control and congenital
      anomaly or congenital anomaly. We included original papers in English published
      after 1997 with data on congenital malformations and HbA1c in at least 250 women
      with pregestational diabetes. RESULTS: Nine papers with in total 6225 women with
      type 1 diabetes and 2334 women with type 2 diabetes were included. The prevalence
      of congenital malformations was 6.4% in women with type 1 diabetes and 4.3% in
      women with type 2 diabetes and for the combined group of women with
      pregestational diabetes, the relative risk compared to the background population
      was 3.2. In women with HbA1c < 53 mmol/mol (7.0%) in early pregnancy or HbA1c 53
      64 mmol/mol (7.0-8.0%) the prevalence of congenital malformations was 4.3 and
      3.7%, respectively, with a relative risk of 2.2 and 1.9, respectively.
      CONCLUSIONS: In pregnant women with pregestational diabetes the prevalence of
      congenital abnormalities was threefold higher in women with pregestational
      diabetes compared to the background population. However, HbA1c below 53 mmol/mol
      (7.0%) in early pregnancy was also associated with a two times increased risk of
      congenital malformations compared to the background population.

PMID- 29172828
TI  - Influence of adjunctive lacosamide in patients with seizures: a systematic review
      and meta-analysis.
AB  - INTRODUCTION: Adjunctive lacosamide treatment might be promising to treat
      seizures. However, the results remained controversial. We conducted a systematic
      review and meta-analysis to compare the efficacy and safety of adjunctive
      lacosamide versus placebo in patients with seizures. METHODS: PubMed, EMbase, Web
      of science, EBSCO and Cochrane library databases were systematically searched.
      Randomized controlled trials (RCTs) assessing the effect of adjunctive lacosamide
      versus placebo on seizures were included. Two investigators independently
      searched articles, extracted data and assessed the quality of included studies.
      The primary outcomes were 50% responder rate and seizure freedom. RESULTS: Four
      RCTs involving 1199 patients were included in the meta-analysis. Overall,
      compared with placebo treatment, adjunctive lacosamide treatment was associated
      with a significantly increased 50% responder rate (RR = 1.89; 95% CI = 1.51-2.36;
      P < 0.00001) and seizure freedom (RR = 4.97; 95% CI = 1.78-13.91; P = 0.002), but
      improved dizziness (RR = 3.97; 95% CI = 2.91-5.42; P < 0.00001), nausea (RR =
      2.85; 95% CI = 1.75-4.66; P < 0.0001), vomiting (RR = 4.11; 95% CI = 2.23-7.57; P
      < 0.00001), diplopia (RR = 6.85; 95% CI = 3.36-13.94; P < 0.00001), treatment
      emergent adverse events (RR = 2.29; 95% CI = 1.93-2.71; P < 0.00001) and serious
      adverse events (RR = 2.52; 95% CI = 1.33-4.78; P = 0.005). CONCLUSIONS: Compared
      to placebo, adjunctive lacosamide resulted in a significantly improved 50%
      responder rate and seizure freedom, but with increased dizziness, nausea,
      vomiting, diplopia, treatment-emergent adverse events and serious adverse events.

PMID- 29172829
TI  - Formulation and optimization of duloxetine hydrochloride buccal films: in vitro
      and in vivo evaluation.
AB  - Duloxetine hydrochloride (DH) is a serotonin-norepinephrine reuptake inhibitor
      (SSNRI) indicated for the treatment of depression. Duloxetine suffers from
      reduced oral bioavailability (~50%) due to hepatic metabolism. This study aims to
      develop DH buccoadhesive films to improve its bioavailability. DH buccoadhesive
      films were prepared adopting the solvent casting method using hydroxypropyl
      methylcellulose (HPMC) and polyvinyl alcohol (PVA). The prepared films were
      evaluated for weight uniformity, drug content, surface pH, swelling index,
      mucoadhesion strength and drug release percentages. Accelerated stability and
      bioavailability studies in healthy human volunteers were also performed for the
      selected films. Results of the evaluation tests showed that the optimum
      physicochemical characters were obtained by the films prepared with 2% HPMC using
      10% propylene glycol (F2 films). Accelerated stability studies revealed that DH
      showed proved stability throughout the experiment time. DH bioavailability from
      F2 films was determined and compared with that of the marketed oral capsules
      (Cymbalta(r) 30 mg). The pharmacokinetic results showed that Cmax for F2 was
      higher than the market product. In addition, ANOVA analysis showed that a Tmax of
      F2 film was significantly lower, while, the AUC0-72 of F2 was significantly
      higher than that of Cymbalta capsules. The percentage relative bioavailability of
      DH from F2 was found to be 296.39%. Therefore, the prepared buccal films offer an
      alternative route for the administration of DH with the possibility of improving
      its bioavailability.

PMID- 29172830
TI  - Like mother like daughter: low birth weight and preeclampsia tend to reoccur at
      the next generation.
AB  - BACKGROUND: Low birth weight and preeclampsia are both adverse pregnancy and
      delivery outcomes, with possible influence on future health status. Previous
      studies have shown that intergenerational factors may be important prognostic
      information in evaluating women prior to or after conception. Our objective was
      to evaluate the role of intergenerational factors on the incidence of
      preeclampsia and low birth weight (LBW). METHODS: A retrospective population
      based study was conducted. Perinatal information was gathered from 2311 familial
      triads, comprising mothers (F1), daughters (F2), and children (F3). All births
      occurred in a tertiary medical center between 1991 and 2013. A multivariate
      generalized estimating equation logistic regression model analysis was used to
      study the association between LBW and preeclampsia across generations while
      controlling for confounders and for clusters of families in the database.
      RESULTS: A total of 1490 in F1, 1616 in F2, and 2311 in F3 were included. LBW in
      mothers (F2), adjusted for possible confounders, was found to be a significant
      predictor for LBW in offspring (OR = 1.6, 95% CI 1.02-2.6, p = .043). Likewise,
      preeclampsia was also noted as a significant intergenerational factor following
      adjustments for possible confounders (OR = 2.9, 95% CI 1.4-5.8, p = .004).
      CONCLUSIONS: Maternal LBW and preeclampsia are both independent risk factors for
      recurrence in the next generation.

PMID- 29172831
TI  - The placental bed vascular pathology revisited: a risk indicator for
      cardiovascular disease.
AB  - AIM: The present paper intends in the first place to clarify the confusing
      terminology for describing the vascular pathology of the placental bed in
      relation to long-term risk of cardiovascular disease. METHODS: Systematic review
      of relevant topics. RESULTS: The maternal blood supply to the placenta is
      achieved by some 100 utero-placental spiral arteries with an outside diameter
      varying between 200 and 600 microns. Defective physiological changes of the
      myometrial segment of utero-placental spiral arteries and, particularly in
      preeclampsia associated to hypertensive disease, the presence of atherosclerosis
      in their proximal segment are a cause of obstructive vascular pathology. On the
      other hand, basal arteries which supply the inner myometrium and basal decidua
      are not affected by physiological change and maintain their musculoelastic
      structure. They can be identified by their external diameter of less than 120
      microns. Acute atherosis is an aspecific vascular lesion that occurs in basal as
      well as spiral arteries inside, as well as outside, the placental bed in
      association with a variety of obstetrical conditions. CONCLUSIONS: An increased
      risk of future cardiovascular disease, should be linked to atherosis or, at a
      later stage, atherosclerosis of utero-placental spiral arteries, rather than to
      that of decidual basal arteries.

PMID- 29172833
TI  - A systematic review of targeted agents for non-small cell lung cancer.
AB  - BACKGROUND: advanced-stage non-small cell lung cancer (NSCLC) is characterized by
      having limited treatment options and thus a poor prognosis. However, new
      treatment options, in the form of targeted agents (TA), have emerged during
      recent years. This systematic review aims to provide an overview of the
      accessible literature in PubMed evaluating TA used on NSCLC patients, and the
      resulting survival outcomes. METHOD: this systematic literature review was
      conducted by reviewing all relevant literature in PubMed. Six separate searches
      were performed: Three searches where controlled entry terms were used and three
      free text searches. Furthermore, other relevant publications were included
      manually. A total of seventy-two studies met the search criteria and were thus
      further analyzed and evaluated. RESULTS: In the included studies, various TAs and
      their effect on different molecular targets have been evaluated. Clinical
      responses vary considerably among the different genetic aberrations. The majority
      of studies evaluated TA for epidermal growth factor receptor (EGFR) mutations and
      TA for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma
      kinase (EML4-ALK) rearrangements. Studies regarding the use of TA for Rat sarcoma
      (RAS), rapidly accelerated fibrosarcoma (RAF), ROS proto-oncogene 1 (ROS1)
      rearrangement, Receptor tyrosine-protein kinase erbB-2 (ERBB2),
      Phosphatidylinositol 3-kinase (PIK3CA)/v-akt murine thymoma viral oncogene
      homolog; protein kinase B(AKT)/Phosphatase and tensin homolog deleted on
      chromosome 10(PTEN), The mammalian target of rapamycin (mTOR), and Mesenchymal
      epithelial transition factor (MET) were included as well. In general, studies
      comparing treatment outcomes in EGFR-mutated patients and EML4-ALK (ALK)
      rearranged patients after use of either TA or standard chemotherapy, present
      significant better results after TA. CONCLUSIONS: This systematic review provides
      an overview of available literature in PubMed regarding NSCLC and TA. Included
      studies point toward that TA appears to be a promising therapeutic tool in
      treating NSCLC patients and use of TA is expected to result in improved treatment
      outcomes.

PMID- 29172832
TI  - The 17D-204 and 17DD yellow fever vaccines: an overview of major similarities and
      subtle differences.
AB  - INTRODUCTION: The yellow fever vaccine is a live attenuated virus vaccine that is
      considered one of the most efficient vaccines produced to date. The original 17D
      strain generated the substrains 17D-204 and 17DD, which are used for the current
      production of vaccines against yellow fever. The 17D-204 and 17DD substrains
      present subtle differences in their nucleotide compositions, which can
      potentially lead to variations in immunogenicity and reactogenicity. We will
      address the main changes in the immune responses induced by the 17D-204 and 17DD
      yellow fever vaccines and report similarities and differences between these
      vaccines in cellular and humoral immunity . This is a relevant issue in view of
      the re-emergence of yellow fever in Uganda in 2016 and in Brazil in the beginning
      of 2017. Areas covered: This article will be divided into 8 sections that will
      analyze the innate immune response, adaptive immune response, humoral response,
      production of cytokines, immunity in children, immunity in the elderly, gene
      expression and adverse reactions. Expert commentary: The 17D-204 and 17DD yellow
      fever vaccines present similar immunogenicity, with strong activation of the
      cellular and humoral immune responses. Additionally, both vaccines have similar
      adverse effects, which are mostly mild and thus are considered safe.

PMID- 29172834
TI  - Managing and maintaining bone mineral density in diabetes patients with
      pharmacotherapy.
AB  - INTRODUCTION: The population of patients with osteoporosis and diabetes is
      increasing as the aging population increases. Loss of bone mineral density occurs
      in patients with diabetes, but is not always a priority in the practice setting.
      The aim of this review is to discuss clinical considerations when managing
      osteoporosis in patients with diabetes. Areas covered: The pathophysiology of
      decreased bone mineral density in patients with diabetes is discussed.
      Additionally, diabetic risk factors for fracture, such as hypoglycemia, the
      National Osteoporosis Foundation recommendations for osteoporosis, and secondary
      causes of osteoporosis, including disease and medication related causes, are
      discussed. Furthermore, recommendations for antihyperglycemic agents,
      thiazolidinediones, canagliflozin, insulin, metformin, and sitagliptin are
      discussed due to their effects on bone mineral density. Expert opinion: Even
      though diabetes is an important risk factor for osteoporosis, assessing bone
      health in diabetic patients is often overlooked. Ensuring adequate prevention and
      treatment strategies for osteoporosis is vitally important with our diabetic
      patients as the population ages. T-scores and FRAX scores likely underrepresent a
      diabetic patients risk for fracture, and this should be taken into consideration
      in treatment decisions. Future studies are needed to determine optimal
      pharmacologic treatment of hyperglycemia in this population.

PMID- 29172835
TI  - Prevalence of hyperhomocysteinemia and its associated factors in patients with
      primary hypertension in Chinese urban communities: A cross-sectional study from
      Nanjing.
AB  - OBJECTIVE: This study aimed to investigate the prevalence of hyperhomocysteinemia
      (Hhcy) and its major determinants in Chinese urban population with new-onset
      hypertension. METHODS: A total of 574 adults (404 men and 170 women) with newly
      diagnosed primary hypertension were recruited from seven communities in Nanjing,
      China. Data on lifestyle factors, such as physical activities, current smoking
      and drinking status, dietary habits, and familial factors were collected in
      interviews, and laboratory examinations were performed by well-trained personnel.
      Potential factors related to the prevalence of Hhcy in this population were
      analyzed using a logistic regression model. RESULTS: Of the 574 participants, 421
      (73.3%) were diagnosed with Hhcy whereas the remainder were only hypertensive.
      The study highlighted a number of factors that were significantly correlated (p <
      0.001) with the prevalence of Hhcy. Subjects with Hhcy were more likely to be
      male (odds ratio [OR] 3.007, 95% confidence interval [CI] 1.781-5.079), have a
      smoking history (OR 1.052, 95% CI 1.031-1.074), older (OR 1.052, 95% CI 1.031
      1.074), have an elevated Body Mass Index BMI (OR 1.160, 95% CI 1.080-1.246) and
      higher levels of low density lipoprotein cholesterol (LDL-c) (OR 1.590, 95% CI
      1.226-2.063). Regular and adequate physical activity was associated with normal
      homocysteine levels in both male and female groups (p < 0.05). For males only,
      having a higher BMI, higher LDL-c or being older significantly (p < 0.05)
      affected the chances of Hhcy. Whereas for females, lower levels of eGFR could be
      related to Hhcy (p < 0.05). CONCLUSIONS: Our present study reported a high
      prevalence of Hhcy in the Nanjing population with new-onset hypertension.
      Associated factors like physical activity, gender, smoking history, age, BMI, and
      LDL-c were important modifiers of plasma homocysteine concentration. Management
      and intervention of the above associated factors should be implicated to improve
      H type hypertension control.

PMID- 29172837
TI  - Biphasic insulin aspart 30 treatment for people with type 2 diabetes: a budget
      impact analysis based in Thailand.
AB  - OBJECTIVE: To assess the financial consequences of different adoption rate of
      Biphasic Insulin Aspart (BIAsp) 30 instead of Biphasic Human Insulin (BHI) 30 for
      people with type 2 diabetes (T2DM) in Thailand from the payer's perspective.
      METHODS: The Excel-based International T2DM Budget Impact Model over a 3-year
      period was used. The cohort was the T2DM patients who received treatment from
      government hospitals under the Universal Health Coverage Scheme. Demographic, the
      adverse events, and the costs were derived from published studies in Thailand.
      Efficacy was based on meta-analysis. Adoption rates were assumed to increase each
      year. Net budget impact (NBI) and one-way sensitivity were analyzed. RESULTS:
      Hypoglycemia costs were lower in BIAsp 30 compared with BHI 30. The NBI per year
      was 26,511,269 THB (771,349 USD) for year 1, 52,181,133 THB (1,518,218 USD) for
      year 2, and 76,189,608 THB (2,216,747 USD) for year 3. The NBI per insulin user
      per year was 33.45 THB (0.97 USD), 67.27 THB (1.96 USD), 101.49 THB (2.95 USD)
      from year 1 to year 3, respectively Conclusions: Lower rate of hypoglycemia with
      BIAsp 30 than those treated with BHI 30 generates cost savings resulting in
      significant deduction in the additional acquisition cost of BIAsp 30. Therefore,
      the NBI per insulin user per year has become small.

PMID- 29172836
TI  - Ectonucleotidase CD39 expression in regional metastases in head and neck cancer.
AB  - INTRODUCTION: CD39 is the rate-limiting enzyme in the generation of
      immunosuppressive adenosine and its expression and activity are significant in
      tumor progression. Squamous cell carcinoma of the head and neck (HNSCC) shows an
      overall poor prognosis due to high local recurrence rates and early metastatic
      spread. MATERIAL AND METHODS: Primary tumor specimens and lymph node specimens
      harvested during neck dissection of 65 patients with a diagnosis of HNSCC were
      subjected to immunohistochemical and H-score analysis of CD39 expression.
      Demographics, histopathology and subsequent outcome were analyzed. RESULTS: The
      primary cancer was squamous cell carcinoma in all patients (male/female 55:10). H
      score for CD39 expression in the primary lesion and metastatic lymph nodes was
      significantly higher in advanced compared to early stages with no significant
      differences among different tumor locations. High intratumoral and
      intrametastatic CD39 expression was associated with an inferior patients' overall
      survival at a mean follow-up of 83.4 months (6-204 months). CONCLUSION: CD39
      expression in HNSCC correlated positively with tumor stage and appears to predict
      poor prognosis. Therefore, CD39 expression in primary lesions and metastatic
      lymph nodes seems to identify patients at high risk in HNSCC of all tumor sites.
      Immunotherapeutic approaches targeting CD39 might be promising for this patient
      population.

PMID- 29172838
TI  - In vitro schistosomicidal activity of the lignan (-)-6,6'-dinitrohinokinin (DNHK)
      loaded into poly(lactic-co-glycolic acid) nanoparticles against Schistosoma
      mansoni.
AB  - CONTEXT: (-)-6,6'-Dinitrohinokinin (DNHK) display remarkable antiparasitic
      activity and was, therefore, incorporated into a nanoparticle formulation.
      OBJECTIVE: Incorporation of DNHK in poly lactic-co-glycolic acid (PLGA)
      nanoparticles aiming to improve its biological activities. MATERIALS AND METHODS:
      Synthesis, characterization and incorporation of DNHK into glycolic acid (PLGA)
      nanoparticles by nanoprecipitation method. The nanoparticles were characterized
      by ultraviolet-visible spectroscopy, X-ray diffraction, field emission electron
      microscopic scanning mansoni (FESEM), and dynamic light scattering (DLS). For the
      in vitro test with Schistosoma mansoni, the DNHK-loaded PLGA was diluted into the
      medium, and added at concentrations 10-200 uM to the culture medium containing
      one adult worm pair. The parasites were kept for 120 h and monitored every 24 h
      to evaluate their general condition, including: pairing, alterations in motor
      activity and mortality. RESULTS: The loaded PLGA nanoparticles gave an
      encapsulation efficiency of 42.2% and showed spherical characteristics in
      monodisperse polymeric matrix. The adult worm pairs were separated after 120 h of
      incubation for concentrations higher than 50 uM of DNHK-loaded PLGA. The groups
      incubated with 150 and 200 uM of DNHK-loaded PLGA for 24 and 120 h killed 100% of
      adult worms, afforded LC50 values of 137.0 +/- 2.12 uM and 79.01 +/- 1.90 uM,
      respectively, which was similar to the effect displayed by 10 uM of praziquantel.
      DISCUSSION AND CONCLUSIONS: The incorporation of DNHK-loaded showed
      schistosomicidal activity and allowed its sustained release. The loaded PLGA
      system can be administered intravenously, as well as it may be internalized by
      endocytosis by the target organisms.

PMID- 29172839
TI  - Assessment of evidence for nanosized titanium dioxide-generated DNA strand breaks
      and oxidatively damaged DNA in cells and animal models.
AB  - Nanosized titanium dioxide (TiO2) has been investigated in numerous studies on
      genotoxicity, including comet assay endpoints and oxidatively damaged DNA in cell
      cultures and animal models. The results have been surprisingly mixed, which might
      be attributed to physico-chemical differences of the tested TiO2. In the present
      review, we assess the role of certain methodological issues and publication bias.
      The analysis shows that studies on DNA strand breaks without proper assay
      controls or very low intra-group variation tend to show statistically significant
      effects. Levels of oxidatively damaged DNA, measured by the enzyme-modified comet
      assay, tend to show no effect in studies that have not included proper assay
      controls or they have uncertainty about the measurement. In addition, there are
      indications of publication and reporting bias. Nevertheless, the analysis shows
      that Aeroxide P25 generates DNA strand breaks in a concentration-dependent
      manner, which is not dependent on the duration of exposure. The standard comet
      assay seems to be able to discriminate between the genotoxicity of different
      types of TiO2, where anatase TiO2 seems to be the form with strongest genotoxic
      potential. Cell culture studies also demonstrate increased levels of oxidatively
      damaged DNA after exposure to TiO2. There are relatively few studies on animal
      models where DNA strand breaks and oxidatively damaged DNA have been tested with
      reliable methods. Collectively, this review shows that exposure to nanosized TiO2
      is associated with genotoxicity in cells, whereas there are still too few
      reliable studies to assess the genotoxic potential in animal models.

PMID- 29172840
TI  - The influence of oral statin medications on progression of glaucomatous visual
      field loss: A propensity score analysis.
AB  - PURPOSE: The purpose of this study was to examine the association between oral
      statin use and the progression of open angle glaucoma. METHODS: Medical records
      of 847 Veterans were reviewed to collect statin use history, record demographic
      and comorbid medical conditions, and review visual fields. Visual field
      progression was judged by an ophthalmologist masked to statin use history.
      Progression rates in a propensity score matched cohort were compared between
      statin users and nonusers using McNemar's test with the propensity model derived
      using associated medical and demographic factors. RESULTS: The mean length of
      observation was 1324 days with a standard deviation of 464 days. Thirty-one per
      cent of Veterans demonstrated glaucomatous progression in at least one eye, 49%
      did not demonstrate progression, and 20% were indeterminate. Approximately 74% of
      subjects had previously used a statin, with this group having heavier burdens of
      several comorbid medical conditions and less severe baseline glaucoma than
      nonusers. The matched cohort was 196 statin users and 196 nonusers, each with
      similar baseline characteristics (standardised differences <0.10). Progression
      rates were 35% for statin users compared to 56% for nonusers in the matched
      cohort (McNemar's p<0.001). CONCLUSIONS: In this population of Veterans, glaucoma
      patients with any history of statin use have lower visual field progression rates
      than statin nonusers.

PMID- 29172841
TI  - Anti-inflammatory effects of Artemisia scoparia and its active constituent, 3,5
      dicaffeoyl-epi-quinic acid against activated mast cells.
AB  - OBJECTIVES: Artemisia scoparia Waldst. et Kit. (AS) has been used to treat
      inflammation, urticaria and hepatitis. However, the scientific studies of AS and
      its active compound for inflammatory reactions in activated human mast cell line,
      HMC-1 cells have not yet been elucidated. MATERIALS AND METHODS: Here, we
      isolated 3,5-dicaffeoyl-epi-quinic acid (DEQA) from AS butanol fraction. The anti
      inflammatory effect of AS and its new active compound, DEQA was examined in HMC-1
      cells by studying the following markers: phorbol 12-myristate 13-acetate and
      calcium ionophore A23187 (PMACI)-induced thymic stromal lymphopoietin (TSLP),
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 secretion and
      mRNA expression by ELISA and RT-PCR, respectively. Furthermore, mechanism related
      to anti-inflammatory was examined by Western blotting. RESULTS: We reported that
      AS and its new active compound, DEQA significantly reduced TSLP, TNF-alpha, IL
      1beta and IL-6 production levels through the reduction of caspase-1 activity. The
      mRNA expression of these inflammatory cytokine was also reduced via blocking
      nuclear factor-kappaB nuclear translocation by AS and DEQA. In addition, AS
      significantly reduced phosphorylated-c-Jun N-terminal kinase level and DEQA
      significantly reduced both phosphorylated-c-Jun N-terminal kinase and -p38
      mitogen-activated protein kinase levels. CONCLUSIONS: Therefore, these results
      indicated that AS and its active compound, DEQA may improve mast cell-mediated
      inflammatory diseases.

PMID- 29172842
TI  - Clinical Features of CMV-Associated Anterior Uveitis.
AB  - Cytomegalovirus (CMV) anterior uveitis is the most common ocular manifestation of
      CMV disease in immunocompetent individuals. It is thought to be due to a local
      reactivation of latent CMV and is usually unilateral. The acute form presents as
      Posner-Schlossman Syndrome, a recurrent hypertensive anterior uveitis with few
      granulomatous keratic precipitates. There are geographic differences in the
      chronic form of CMV anterior uveitis. Asian patients commonly present as Fuchs
      Uveitis Syndrome with diffuse stellate keratic precipitates, while the European
      patients present with a chronic hypertensive anterior uveitis with fewer keratic
      precipitates that are brown in color and located inferiorly. Characteristic
      features of CMV anterior uveitis include mild anterior chamber inflammation,
      elevated intraocular pressure, stromal iris atrophy. Synechiae, macular edema and
      retinitis are typically absent. CMV disease may also be associated with the
      development of corneal endotheliitis with a reduced endothelial cell count. Long
      term complications include glaucomatous optic neuropathy and cataract formation.

PMID- 29172843
TI  - Intra-articular corticosteroid injections in haemophilic arthropathy: are they
      recommended?
AB  - INTRODUCTION: Intra-articular (IA) corticosteroid (CS) injections are commonly
      used in the treatment of osteoarthritis. However, they are rarely utilized in
      haemophilic arthropathy. In fact, the efficacy of this method in haemophilic
      arthropathy is frequently discussed and debated in clinical practice. AIM: To
      investigate the effectiveness of IA CS injections in patients with painful
      haemophilic arthropathy. METHODS: A review of the literature on the topic was
      performed. RESULTS: In osteoarthritis, reports with a high level of evidence
      state that the efficacy of IA injections of CS is controversial. In haemophilic
      arthropathy, some low-level evidence reports seem to indicate that short-term
      pain alleviation can be achieved. CONCLUSIONS: Considering that pain relief after
      IA injections of CS is controversial and that the cost of the haematologic
      treatment required to perform the procedure is high in haemophilic arthropathy,
      we do not recommend the routine use of CS IS injections in haemophilia. Moreover,
      point of care (POC) ultrasound (US)-guided injections are not advised, because
      the injection procedure is so simple that the use of POC-US will unnecessarily
      prolong the duration of the procedure.

PMID- 29172844
TI  - Myopia rates in a genetically isolated population.

PMID- 29172845
TI  - Temporal retinal thinning and the diagnosis of Alport syndrome and Thin basement
      membrane nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Alport syndrome is an inherited disease characterized
      by renal failure, hearing loss, and ocular abnormalities, including temporal
      retinal thinning. This study compared retinal thinning in Alport syndrome and
      other renal diseases. METHODS: Alport syndrome was diagnosed on renal biopsy and
      genetic testing. Subjects underwent optical coherence tomography (OCT)
      (Spectralis OCT, Heidelberg Instruments). Retinal thinning was determined from
      horizontal macular OCT scans through the foveal center using the formula:
      Temporal thickness index (TTI) = (nasal - temporal thickness) / nasal thickness *
      100%, and compared with the normal range for each age group. Statistical analysis
      was performed using Student's t test, Mann-Whitney U test, and ROC analysis
      (SPPS, IBM). RESULTS: The mean temporal retinal thickness index was 12.4 +/- 5.2%
      in men (n = 19) and 7.4 +/- 1.4% in women (n = 28) with X-linked Alport syndrome;
      13.1 +/- 4.5% (n = 4) in recessive disease; 6.4 +/- 2.2% (n = 5) in Thin basement
      membrane nephropathy; and 6.3 +/- 3.3% (n = 14) in other renal diseases. Thinning
      was worse in men than women with X-linked disease (p < 0.01), and worse in men
      who developed early onset renal failure (R2 = 0.75). Temporal retinal thinning
      was 84% sensitive for men with X-linked Alport syndrome and 67% specific (AUC =
      0.83) compared with other renal diseases. CONCLUSIONS: Retinal temporal thinning
      is diagnostic for X-linked Alport syndrome in men and distinguishes them this
      condition from Thin basement membrane nephropathy, but only in men (p = 0.002).
      Temporal retinal thinning may also identify men and women with the rarer
      autosomal recessive disease.

PMID- 29172846
TI  - Use of beta blockers is associated with hearing loss.
AB  - OBJECTIVE: This study was conducted to investigate the hypothesis that patients
      using beta-blockers will develop hearing loss. DESIGN: A cross-sectional study.
      STUDY SAMPLE: A total of 125 patients completed the study. A total of 63 patients
      were on beta-blockers and 62 were not on beta-blockers. RESULTS: Carvedilol was
      significantly associated with hearing loss. Other beta-blockers including
      metoprolol and atenolol showed no association with hearing loss. Linear multiple
      regression analysis was run including variables of gender, age, ischaemic heart
      disease, cardiac failure/dilated cardiomyopathy, frusemide and carvedilol use as
      predictors for total hearing loss severity at all frequencies. Age and gender, as
      well as carvedilol, were found to be the only statistically significant
      predictors for hearing loss severity. CONCLUSION: Chronic use of carvedilol was
      associated with significant hearing loss. This may need to be taken into account
      when prescribing the drug. Further randomised controlled studies with baseline
      audiometric hearing tests before starting treatment, and periodic follow-up
      tests, would provide a better assessment of the effect of carvedilol on hearing.

PMID- 29172847
TI  - Synergies resulting from a systems biology approach: integrating radiation
      epidemiology and radiobiology to optimize protection of the public after exposure
      to low doses of ionizing radiation.

PMID- 29172848
TI  - The role of hormones in muscle hypertrophy.
AB  - Anabolic-androgenic steroids (AAS) and other hormones such as growth hormone (GH)
      and insulin-like growth factor-1 (IGF-1) have been shown to increase muscle mass
      in patients suffering from various diseases related to muscle atrophy. Despite
      known side-effects associated with supraphysiologic doses of such drugs, their
      anabolic effects have led to their widespread use and abuse by bodybuilders and
      athletes such as strength athletes seeking to improve performance and muscle
      mass. On the other hand, resistance training (RT) has also been shown to induce
      significant endogenous hormonal (testosterone (T), GH, IGF-1) elevations.
      Therefore, some bodybuilders employ RT protocols designed to elevate hormonal
      levels in order to maximize anabolic responses. In this article, we reviewed
      current RT protocol outcomes with and without performance enhancing drug usage.
      Acute RT-induced hormonal elevations seem not to be directly correlated with
      muscle growth. On the other hand, supplementation with AAS and other hormones
      might lead to supraphysiological muscle hypertrophy, especially when different
      compounds are combined.

PMID- 29172849
TI  - Postoperative Endophthalmitis: A Review of Risk Factors, Prophylaxis, Incidence,
      Microbiology, Treatment, and Outcomes.
AB  - Postoperative endophthalmitis is one of the most feared complications of
      intraocular surgery. The most common types of intraocular surgeries performed
      worldwide are cataract extraction, glaucoma drainage implants/trabeculectomy, and
      pars plana vitrectomy. This review will focus on the clinical features, risk
      factors, prophylaxis, and treatment of endophthalmitis in these three main
      intraocular surgeries.

PMID- 29172850
TI  - Study on epidemiology of cognitive dysfunction after stroke in the population
      over the age of 45 in Inner Mongolia.
AB  - OBJECTIVE: To analyze the prevalence of different degrees vascular cognitive
      impairment (VCI) in stroke and the characteristics of demography distribution in
      Inner Mongolia. In order to provide reference data and theoretical guidance for
      the prevention and treatment of VCI after stroke in the area. METHODS: Stratified
      multi-stage random sampling was used to extract six regions of Inner Mongolia as
      the first sampling cluster; and then the corresponding banners (counties) were
      selected randomly as the secondary sampling cluster; according to the number of
      patient required to investigation, the corresponding number of communities was
      randomly selected from the secondary sampling cluster. According to the
      diagnostic criteria of 'Guidelines for the diagnosis and treatment of vascular
      cognitive impairment' and National Institute of Neurological Disorders and Stroke
      convened an International Workshop with support from the Association
      Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS
      AIREN), we screened all stroke patients aged 45 or older from each community, a
      total of 444 patients participated in the questionnaire and various scale
      assessments. RESULTS: The prevalence of VCI, vascular cognitive impairment no
      dementia and vascular dementia was 80.41%, 34.46% and 45.95% respectively. The
      prevalence of VCI in stroke was significantly different in different nationality,
      age and education level (P < 0.05), and there was no significant difference in
      gender, occupation, marital status and family structure (P > 0.05). CONCLUSION:
      The prevalence of VCI after stroke was higher in Inner Mongolia, and VCI had a
      relatively high morbidity in old age people and person with less education in
      Chinese Han population.

PMID- 29172851
TI  - Intrinsic subtypes and benefit from postmastectomy radiotherapy in node-positive
      premenopausal breast cancer patients who received adjuvant chemotherapy - results
      from two independent randomized trials.
AB  - BACKGROUND: The study of the intrinsic molecular subtypes of breast cancer has
      revealed differences among them in terms of prognosis and response to
      chemotherapy and endocrine therapy. However, the ability of intrinsic subtypes to
      predict benefit from adjuvant radiotherapy has only been examined in few studies.
      METHODS: Gene expression-based intrinsic subtyping was performed in 228 breast
      tumors collected from two independent post-mastectomy clinical trials (British
      Columbia and the Danish Breast Cancer Cooperative Group 82b trials), where pre
      menopausal patients with node-positive disease were randomized to adjuvant
      radiotherapy or not. All patients received adjuvant chemotherapy and a subgroup
      of patients underwent ovarian ablation. Tumors were classified into intrinsic
      subtypes: Luminal A, Luminal B, HER2-enriched, Basal-like and Normal-like using
      the research-based PAM50 classifier. RESULTS: In the British Columbia study,
      patients treated with radiation had an overall significant lower incidence of
      locoregional recurrence compared to the controls. For Luminal A tumors the risk
      of loco-regional recurrence was low and was further lowered by adjuvant
      radiation. These findings were validated in the DBCG 82b study. The individual
      data from the two cohorts were merged, the hazard ratio (HR) for loco-regional
      recurrence associated with giving radiation was 0.34 (0.19 to 0.61) overall and
      0.12 (0.03 to 0.52) for Luminal A tumors. CONCLUSIONS: In both postmastectomy
      trials, patients with Luminal A tumors turned out to have a significant lower
      incidence of loco-regional recurrence when randomized to adjuvant radiotherapy,
      leaving no indication to omit postmastectomy adjuvant radiation in pre-menopausal
      high-risk patients with Luminal A tumors. It was not possible to evaluate the
      effect of radiotherapy among the other subtypes because of limited sample sizes.

PMID- 29172852
TI  - Sumoylation of the Plant Clock Transcription Factor CCA1 Suppresses DNA Binding.
AB  - In plants, the circadian clock regulates the expression of one-third of all
      transcripts and is crucial to virtually every aspect of metabolism and growth. We
      now establish sumoylation, a posttranslational protein modification, as a novel
      regulator of the key clock protein CCA1 in the model plant Arabidopsis. Dynamic
      sumoylation of CCA1 is observed in planta and confirmed in a heterologous
      expression system. To characterize how sumoylation might affect the activity of
      CCA1, we investigated the properties of CCA1 in a wild-type plant background in
      comparison with ots1 ots2, a mutant background showing increased overall levels
      of sumoylation. Neither the localization nor the stability of CCA1 was
      significantly affected. However, binding of CCA1 to a target promoter was
      significantly reduced in chromatin-immunoprecipitation experiments. In vitro
      experiments using recombinant protein revealed that reduced affinity to the
      cognate promoter element is a direct consequence of sumoylation of CCA1 that does
      not require any other factors. Combined, these results suggest sumoylation as a
      mechanism that tunes the DNA binding activity of the central plant clock
      transcription factor CCA1.

PMID- 29172853
TI  - From the Instructional Insights Editor.
AB  - This article provides updates on the evolution of Instructional Insights as well
      as introductions to both Instructional Insights articles published in this issue.

PMID- 29172854
TI  - Design of composite microparticle systems based on pectin and waste material of
      propolis for modified l-alanyl-l-glutamine release and with immunostimulant
      activity.
AB  - Catabolic conditions like acquired immunodeficiency syndrome, cancer, and burn
      can cause immunosuppression. Amino acids such as alanine and glutamine are
      essential for the activity of the immune system. Propolis is immunostimulant and
      the waste of propolis extraction has been reused with technological and
      therapeutic purposes. Therefore, this study describes the association of propolis
      byproduct extract (BPE) with pectin to prepare spray-dried microparticles
      containing the dipeptide l-alanyl-l-glutamine as stimulant systems of
      neutrophils. The use of a factorial design allowed selecting the best
      formulation, which was characterized by morphology, size, and entrapment
      efficiency analyses. In addition, the systems were characterized by thermal and X
      ray diffraction analysis, Fourier-transform infrared spectroscopy, in vitro drug
      release, and in vitro cytotoxicity and stimulation test of neutrophils. Small
      well-structured microparticles with good entrapment efficiency values were
      achieved. Thermal stability of formulation was observed, and it was proved that
      pectin, BPE and l-alanyl-l-glutamine were dispersed throughout the matrix. The
      drug was released from the microparticles during 24 h governed by swelling and
      diffusion. The drug-loaded formulations showed a significant stimulating effect
      on neutrophils. These structures could increase the activity of immune cells, and
      other in vitro and in vivo studies should be performed in the future.

PMID- 29172855
TI  - Lenalidomide in combination or alone as maintenance therapy following autologous
      stem cell transplant in patients with multiple myeloma: a review of options for
      and against.
AB  - INTRODUCTION: Lenalidomide has multifaceted antimyeloma properties, including
      direct tumoricidal and immunomodulatory effects. Several randomized controlled
      trials have demonstrated improved patient outcomes with lenalidomide maintenance
      after autologous stem cell transplant (ASCT) in patients with newly diagnosed
      multiple myeloma (NDMM). Currently, single-agent lenalidomide is the only
      approved post-ASCT maintenance therapy in the United States and European Union
      for patients with NDMM. Areas covered: This review article summarizes the
      efficacy and safety data of lenalidomide maintenance, as monotherapy and in
      combination with other agents, following ASCT in patients with NDMM. In addition,
      emerging therapies with newer agents in this setting are discussed. Expert
      opinion: Following ASCT, maintenance therapy with lenalidomide until progressive
      disease is an effective and well-tolerated regimen and represents the standard of
      care for patients with NDMM. Studies evaluating maintenance with lenalidomide in
      combination with next-generation proteasome inhibitors, monoclonal antibodies,
      and histone deacetylase inhibitors may further improve patient outcomes.

PMID- 29172856
TI  - Contextual attributes promote or hinder self-regulated learning: A qualitative
      study contrasting rural physicians with undergraduate learners in Japan.
AB  - BACKGROUND AND OBJECTIVES: Previous studies support the notion that East Asian
      medical students do not possess sufficient self-regulation for postgraduate
      clinical training. However, some East Asian physicians who are employed in
      geographically isolated and educationally underserved rural settings can self
      regulate their study during the early phase of their postgraduate career. To
      explore the contextual attributes that contribute to self-regulated learning
      (SRL), we examined the differences in self-regulation between learning as an
      undergraduate and in a rural context in East Asia. METHODS: We conducted
      interviews and diary data collection among rural physicians (n = 10) and
      undergraduates (n = 11) in Japan who undertook self-study of unfamiliar diseases.
      We analyzed three domains of Zimmerman's definition of SRL: learning behaviors,
      motivation, and metacognition using constructivist grounded theory. RESULTS:
      Rural physicians recognized their identity as unique, and as professionals with a
      central role of handling diseases in the local community by conducting self
      study. They simultaneously found themselves being at risk of providing
      inappropriate aid if their self-study was insufficient. They developed strategic
      learning strategies to cope with this high-stakes task. Undergraduates had a fear
      of being left behind and preferred to remain as one of the crowd with students in
      the same school year. Accordingly, they copied the methods of other students for
      self-study and used monotonous and homogeneous strategies. CONCLUSIONS: Different
      learning contexts do not keep East Asian learners from being self-regulated.
      Awareness of their unique identity leads them to view learning tasks as high
      stakes, and to initiate learning strategies in a self-regulated manner. Teacher
      centered education systems cause students to identify themselves as one of the
      crowd, and tasks as low-stakes, and to accordingly employ non-self-regulated
      strategies.

PMID- 29172857
TI  - Diagnostic role of cone beam computed tomography for the position of straight
      array.
AB  - OBJECTIVE: To assess the usefulness of cone beam computed tomography (CBCT) for
      characterizing electrode insertion and evaluate the influence of electrode
      insertion status on post-cochlear implantation (CI) outcomes. DESIGN: Twenty-six
      ears with post-CI CBCT scans were included. The devices were MED-EL Flex28 (n =
      21) and Nucleus slim straight (n = 5). The parameters including cochlear duct
      length (CDL), insertion depth angle (IDA), insertion length of electrode (IL),
      and cochlear coverage (CC) were analyzed and compared with aided pure-tone
      threshold (PTA) with implant in free field, and open-set sentence score. RESULTS:
      The mean CDL was 36.8 +/- 1.4 mm. Electrode array was dislocated into scala
      tympani in two ears. The mean IL and IDA were 26.5 +/- 1.9 mm and 541.4 +/- 70.2
      degrees . The mean linear CC (IL/CDL, 0.73 +/- 0.06) was larger than the mean
      angular CC (IDA/900, 0.60 +/- 0.08). The CBCT parameters showed correlation one
      another. While the aided pure-tone threshold was correlated with IL and IDA,
      there were no significant correlations in the open-set sentence score. For the
      postlingually deaf patients with single electrode (Flex 28), the sentence score
      had no significant correlation and the aided PTA was positively correlated with
      IL (R = 0.517, p = .028). CONCLUSIONS: This study validated the CBCT evaluating
      the electrode array position. The CBCT could be helpful for the preoperative
      selection of the optimal array and prediction of the CC.

PMID- 29172859
TI  - Racial/Ethnic Differences in Cigarette Use: The Roles of Mental Illness and
      Health-Care Access/Utilization.
AB  - BACKGROUND: Empirical evidence supports a hypothesis that cigarettes may be used
      to cope with mental illness. Little research, however, addresses how
      race/ethnicity is linked to mental health and cigarette use. OBJECTIVES: This
      study applied the self-medication hypothesis. It asked whether mental status was
      associated, via health-care access/utilization, with the cigarette use outcomes
      of four racial/ethnic groups. It also tested whether race/ethnicity moderated any
      such associations. METHODS: We used nationally representative data from the 2009
      2010 and 2011-2012 National Health and Nutrition Examination Surveys to link
      cigarette use to mental status and health-care access/utilization. The final
      sample included 3827 White respondents, 1635 African-American respondents, 1144
      Mexican-American respondents, and 781 Hispanic American (other than Mexican
      American) respondents. RESULTS: Consistent with earlier research and the self
      medication hypothesis, we observed a positive relationship between cigarette use
      and mental status. Associations of cigarette use and health-care
      access/utilization sometimes failed to take expected directions. CONCLUSIONS: We
      concluded from the findings that race/ethnicity's moderating role in associations
      between cigarette use and health-care access was generally more advantageous to
      Whites than other groups examined. Where treatment is delayed by lack of access
      to, or lack of trust in, care providers, mental health may worsen-and it is often
      minority Americans who lack access and trust. If minority Americans' health is to
      improve, shrinking racial health disparities, then access to adequate health care
      must be available to them, facilitating prompt treatment of mental and other
      illness.

PMID- 29172860
TI  - Washington State Spirits Privatization: How Satisfied were Liquor Purchasers
      Before and After, and by Type of Retail Store in 2014?
AB  - BACKGROUND: In 2012 Washington State ended a wholesale/retail monopoly on liquor,
      permitting sale of spirits in stores with > 10,000 square feet. Implementation
      resulted in average price increases, but also five times the stores selling
      liquor. OBJECTIVES: As part of a privatization evaluation, we studied pre-post
      and between-store-type purchase experiences. METHODS: A 2010 Washington State
      Liquor Control Board (LCB) survey of liquor purchasers (n = 599), and the 2014
      baseline of a repeated telephone survey (1,202 residents; n = 465 purchasers),
      each included 10 LCB questions on satisfaction with purchase experiences, each
      attribute with graded response scale A = 4 to D = 1 and F (0 = fail). Analyses
      used t-tests for satisfaction differences by time and analysis of variance
      (ANOVA) for 2014 between-store satisfaction-level differences. RESULTS: Five
      purchase features were rated more favorably after privatization (ps < .05-.001),
      including product supply, staff professionalism, location convenience, store
      hours, and prices (though price rated lowest both times); selection offered,
      courtesy, and checkout speed were unaltered, and number of staff and staff
      knowledge declined (both p < .001). Eight consumer experiences differed by store
      type: five satisfaction aspects (supply, selection, number of staff, operating
      hours, and checkout speed) were highest for liquor superstores, while location
      convenience favored grocery and drug stores, and price satisfaction favored
      wholesale (Costco) stores, with staff knowledge highest at liquor stores.
      CONCLUSIONS: Satisfaction with liquor purchases increased after privatization for
      half the consumer experiences. Availability (location convenience and store
      hours) was important to liquor purchasers. Such results are relevant to sustained
      support for the policy of privatizing spirits retail monopolies.

PMID- 29172861
TI  - The benefits of sequential testing: Improved diagnostic accuracy and better
      outcomes for failing students.
AB  - INTRODUCTION: In recent decades, there has been a move towards standardized
      models of assessment where all students sit the same test (e.g. OSCE). By
      contrast, in a sequential test the examination is in two parts, a "screening"
      test (S1) that all candidates take, and then a second "test" (S2) which only the
      weaker candidates sit. This article investigates the diagnostic accuracy of this
      assessment design, and investigates failing students' subsequent performance
      under this model. METHODS: Using recent undergraduate knowledge and performance
      data, we compare S1 "decisions" to S2 overall pass/fail decisions to assess
      diagnostic accuracy in a sequential model. We also evaluate the longitudinal
      performance of failing students using changes in percentile ranks over a full
      repeated year. FINDINGS: We find a small but important improvement in diagnostic
      accuracy under a sequential model (of the order 2-4% of students misclassified
      under a traditional model). Further, after a resit year, weaker students'
      rankings relative to their peers improve by 20-30 percentile points. DISCUSSION:
      These findings provide strong empirical support for the theoretical arguments in
      favor of a sequential testing model of assessment, particularly that diagnostic
      accuracy and longitudinal assessment outcomes post-remediation for the weakest
      students are both improved.

PMID- 29172862
TI  - Comparison of Two Methods: Spinal Anesthesia and Ischiorectal Block on Post
      Hemorrhoidectomy Pain and Hospital Stay: A Randomized Control Trial.
AB  - OBJECTIVE: Hemorrhoidectomy is one of the most common hemorrhoid surgery. Many
      areas are innervated by nerves, and this makes the surgery to be very painful.
      Various anesthetic methods have been proposed, and the number of investigations
      and procedures demonstrated the absence of a reliable method for reducing pain.
      This study compares the cavity ischiorectal block with spinal anesthesia in
      reducing postoperative pain, analgesic consumption, and hospital stay. RESEARCH
      DESIGN: This study is a randomized control trial carried out on seventy patients
      sampled. Thirty-five (35) among them were placed in spinal anesthesia group, and
      the other 35 were placed in the ischiorectal block group. According to the study,
      questionnaire was designed in such a way that postoperative variables such as
      postoperative pain, analgesic consumption, changes in blood pressure, heart rate
      and hospital stay in both groups were evaluated and compared. CLINICAL TRIAL
      REGISTRATION: IRCT2015111616516N3 (
      http://en.search.irct.ir/search?query=IRCT2015111616516N3 ) Results: In this
      study, the pain scores on Visual Analogue Scale (VAS) at 0, 6, 12, and 24 hr for
      spinal anesthesia group after surgery were 0, 3.08 +/- 0.78, 2.05 +/- 1.02, 1.11
      +/- 0.83, respectively (p < 0.05). That of ischiorectal blocks were 0.98 +/-
      0.25, 1.57 +/- 0.81, 0.91 +/- 0.91, and 0.63 +/- 0.31 respectively, which
      indicated lesser pain after surgery in the ischiorectal block at 6, 12, and 24
      hr. In this study, out of the 35 patients that underwent spinal anesthesia, 28
      patients (80%) were hospitalized in the first 6 hr, 13 patients (37.1%) in the
      second 6 hr, 3 patients (8.6%) in the second 12 hr after surgery. For patients
      under the ischiorectal block, the number of patients hospitalized were 13
      patients (37.1%), in the first 6 hr, 4 patients (11.4%) in the second 6 hr, and 1
      (2.9%) were hospitalized in the second 12 hr after surgery (p < 0.05).
      CONCLUSION: Ischiorectal blocks causes less pain, require fewer painkillers, and
      reduces the hospital stay after surgery than spinal anesthesia.

PMID- 29172863
TI  - Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer:
      American Society of Clinical Oncology Clinical Practice Guideline Update.
AB  - Purpose To update the guideline recommendations on the use of larynx-preservation
      strategies in the treatment of laryngeal cancer. Methods An Expert Panel updated
      the systematic review of the literature for the period from January 2005 to May
      2017. Results The panel confirmed that the use of a larynx-preservation approach
      for appropriately selected patients does not compromise survival. No larynx
      preservation approach offered a survival advantage compared with total
      laryngectomy and adjuvant therapy as indicated. Changes were supported for the
      use of endoscopic surgical resection in patients with limited disease (T1, T2)
      and for initial total laryngectomy in patients with T4a disease or with severe
      pretreatment laryngeal dysfunction. New recommendations for positron emission
      tomography imaging for the evaluation of regional nodes after treatment and best
      measures for evaluating voice and swallowing function were added. Recommendations
      Patients with T1, T2 laryngeal cancer should be treated initially with intent to
      preserve the larynx by using endoscopic resection or radiation therapy, with
      either leading to similar outcomes. For patients with locally advanced (T3, T4)
      disease, organ-preservation surgery, combined chemotherapy and radiation, or
      radiation alone offer the potential for larynx preservation without compromising
      overall survival. For selected patients with extensive T3 or large T4a lesions
      and/or poor pretreatment laryngeal function, better survival rates and quality of
      life may be achieved with total laryngectomy. Patients with clinically involved
      regional cervical nodes (N+) who have a complete clinical and radiologic imaging
      response after chemoradiation do not require elective neck dissection. All
      patients should undergo a pretreatment baseline assessment of voice and
      swallowing function and receive counseling with regard to the potential impact of
      treatment options on voice, swallowing, and quality of life. Additional
      information is available at www.asco.org/head-neck-cancer-guidelines and
      www.asco.org/guidelineswiki .

PMID- 29172864
TI  - Management of feline tibial diaphyseal fractures using orthogonal plates
      performed via minimally invasive plate osteosynthesis.
AB  - Objectives The objective was to assess the medium- and long-term outcomes
      (radiographic and owner questionnaire) of feline tibial diaphyseal fractures with
      orthogonal plate fixation via a minimally invasive plate osteosynthesis (MIPO)
      approach. Methods Medical records and radiographs of cats that had tibial
      diaphyseal fractures stabilised with orthogonal plates were obtained (2012-2016).
      Immediate postoperative radiographs were reviewed to assess the construct
      configuration and follow-up radiographs (where available) were used to assess
      bone healing and implant-related complications. An owner-completed questionnaire
      (feline musculoskeletal pain index [FMPI]) was used at a minimum of 6 months
      following surgery to assess the cats' ability to perform normal activities.
      Results Eight feline tibial diaphyseal fractures met the inclusion criteria. One
      major complication was observed, most likely due to an operative technical error.
      There were no further complications following revision surgery. Six of the eight
      cases that had radiographic follow-up either had clinical bone union or showed
      evidence of bone healing. All cases were classified as successful according to
      FMPI. Conclusions and relevance Orthogonal plating of feline tibial diaphyseal
      fractures via an MIPO approach resulted in successful outcomes and a lower
      complication rate compared with previously reported techniques.

PMID- 29172865
TI  - MAMMOTh: A new database for curated mathematical models of biomolecular systems.
AB  - MOTIVATION: Living systems have a complex hierarchical organization that can be
      viewed as a set of dynamically interacting subsystems. Thus, to simulate the
      internal nature and dynamics of the entire biological system, we should use the
      iterative way for a model reconstruction, which is a consistent composition and
      combination of its elementary subsystems. In accordance with this bottom-up
      approach, we have developed the MAthematical Models of bioMOlecular sysTems
      (MAMMOTh) tool that consists of the database containing manually curated MAMMOTh
      fitted to the experimental data and a software tool that provides their further
      integration. RESULTS: The MAMMOTh database entries are organized as building
      blocks in a way that the model parts can be used in different combinations to
      describe systems with higher organizational level (metabolic pathways and/or
      transcription regulatory networks). The tool supports export of a single model or
      their combinations in SBML or Mathematica standards. The database currently
      contains 110 mathematical sub-models for Escherichia coli elementary subsystems
      (enzymatic reactions and gene expression regulatory processes) that can be
      combined in at least 5100 complex/sophisticated models concerning more complex
      biological processes as de novo nucleotide biosynthesis, aerobic/anaerobic
      respiration and nitrate/nitrite utilization in E. coli. All models are
      functionally interconnected and sufficiently complement public model resources.
      AVAILABILITY: http://mammoth.biomodelsgroup.ru.

PMID- 29172867
TI  - Substance Use in Healthcare Workers: Importance of Stress Perception, Smoking
      Temptation, Social Support, and Humor.
AB  - BACKGROUND: Research indicates healthcare workers' personal substance use may
      affect quality of care. Investigating factors that correlate with coping through
      substance use may provide insight into improving quality care. OBJECTIVES: This
      study aims to examine potential correlates of coping through substance use among
      healthcare workers, with a particular focus on humor, social support, stress
      perception, and smoking temptation. METHOD: Participants, recruited from
      healthcare facilities, anonymously completed a 30-minute questionnaire of
      psychometrically valid measurements. RESULTS: In a sample of primarily female
      (75.7%), age 20-39 (74.8%), floor staff (i.e., doctors, nurses,
      technicians/assistants; 61.2%), perceived stress [beta = .036, t(98) = 2.55, p =
      .012], smoking temptation [beta = .036, t(98) = 2.21, p = .030], and coping
      through humor [beta = .163, t(98) = 2.033, p = .045] were significant correlates
      of the coping through substance use, with all relationships positively co
      varying. Social support at work did not predict coping through substance use
      [beta = -.032, t(98) = -.814, p > .05]. Furthermore, negative affect/situation
      smoking temptation was associated with increased coping through substance use
      [beta = .246, t(99) = 2.859, p = .005] and habit/craving temptation was
      associated with decreased coping through substance use [beta = -.260, t(99) = 
      2.201, p = .030; however, positive affect/social temptation was not [beta = .054,
      t(99) = -.553, p > .05]. Conclusions/Importance: These findings suggest that
      coping with humor may relate to coping through substance use, while social
      support at work is either unrelated to coping through substance use in this
      sample or may not be adequately assessed with the measure used. Consistent with
      the literature, negative affect/situation was associated with increased coping
      through substance use. However, habit/craving was negatively predictive. Further
      research should explore the variables related to coping through substance use
      among healthcare workers.

PMID- 29172868
TI  - Treatment for patients with relapsed/refractory mantle cell lymphoma: European
      based recommendations.
AB  - Patients with mantle cell lymphoma (MCL) usually respond to initial combination
      chemotherapy, but the disease inevitably relapses and often follows an aggressive
      course. Here, clinical study results published since 2008 for patients with
      relapsed/refractory MCL were reviewed to compare available evidence for treatment
      guidance. Most trials identified were non-randomized, phase II studies performed
      at a limited number of sites, and many evaluated MCL as one of multiple non
      Hodgkin lymphoma subtypes. Additional randomized, comparative trials are needed.
      Treatment selection generally depends on patient need, age and fitness, time of
      relapse, and line of therapy. Combination regimens typically produce higher
      response rates than single agents, and adding rituximab generally improves
      outcomes. The inclusion of ibrutinib, lenalidomide, temsirolimus, and bortezomib,
      represents an important advance for patients ineligible for, unable to tolerate,
      or failing high-intensity combination chemotherapy. A high need for effective
      treatments in relapsed/refractory MCL remains, particularly for elderly and frail
      patients.

PMID- 29172866
TI  - Radiosensitization of ultrasmall GNP-PEG-cRGDfK in ALTS1C1 exposed to therapeutic
      protons and kilovoltage and megavoltage photons.
AB  - PURPOSE: One of the promising radiosensitizers is the ultrasmall gold
      nanoparticle (GNP) with a hydrodynamic diameter <3 nm. We studied functionalized
      ultrasmall GNPs (1.8 nm diameter) coated by polyethylene glycol (PEG) and
      conjugated with cyclic RGDfK (2.6 nm hydrodynamic diameter) for targeting of
      alpha(v) beta(3) integrin (alphavbeta3) in the murine ALTS1C1 glioma cell line.
      MATERIALS AND METHODS: We investigated the uptake, toxicity and radiosensitivity
      of GNP-PEG-cRGDfKs in ALTS1C1 cells exposed to protons, kilovoltage photons and
      megavoltage photons. The in vitro uptake and toxicity of GNPs in the hepatocytes
      and Kupffer cells were assessed for murine AML12 hepatocyte and RAW 264.7
      macrophage cell lines. The in vivo biodistribution of GNPs in the ALTS1C1 tumor
      model was tested using the inductively coupled plasma mass spectrometry. RESULTS:
      Results indicated GNPs accumulated in the cytoplasm with negligible toxicity for
      a moderate concentration of GNPs. Observed sensitizer enhancement ratios and dose
      enhancement factors are 1.21-1.66 and 1.14-1.33, respectively, for all
      radiations. CONCLUSION: Ultrasmall GNP-PEG-cRGD can be considered as a
      radiosensitizer. For radiotherapy applications, the delivery method should be
      developed to increase the GNP uptake in the tumor and decrease the uptakes in
      undesirable organs.

PMID- 29172869
TI  - Relationship between Tobacco Craving and Quality of Life among French Students:
      Results of a Cross-Sectional Study.
AB  - BACKGROUND: Understanding the factors leading to smoking cessation is of primary
      importance in reducing the death burden. Recently introduced in the DSM-5,
      craving is a potentially promising mechanism involved in relapse, but its
      articulation with quality of life and deprivation on tobacco student's consumers
      has never been investigated. OBJECTIVES: Our study explores the relationship
      between tobacco craving and sub-dimensions of quality of life when controlling
      effect of deprivation on a youth population with tobacco consumption. METHOD:
      Comparison between deprived and non-deprived students were conducted with online
      questionnaires on demographic data, level of dependency, perceived quality of
      life, deprivation and craving. Multivariate linear regression with backward
      procedure was conducted to assess the predictive validity of these variables on
      craving. Finally, Bayesian analysis was conducted to evaluate the model proposed
      by the regression. RESULTS: One hundred and seventy-four participants were
      included. Craving was significantly correlated with all the other variables and
      increases when the level of deprivation rises, while it decreases when physical
      health improves. These results are confirmed by Bayesian linear regression.
      Conclusions/Importance: Environmental and social factors are usually overlooked
      when it comes to understanding individuals, deeply rooted biological mechanisms
      such as craving. Working on physical health is of interest to diminished craving
      and improves the quality of life during smoking cessation and thereby to support
      success on the student population. Consequences for the triadic neurocognitive
      model of addiction are discussed.

PMID- 29172870
TI  - Identifying Risk Factors for Drug Use in an Iranian Treatment Sample: A
      Prediction Approach Using Decision Trees.
AB  - INTRODUCTION AND AIM: Substance abuse exacts considerable social and health care
      burdens throughout the world. The aim of this study was to create a prediction
      model to better identify risk factors for drug use. DESIGN AND METHODS: A
      prospective cross-sectional study was conducted in South Khorasan Province, Iran.
      Of the total of 678 eligible subjects, 70% (n: 474) were randomly selected to
      provide a training set for constructing decision tree and multiple logistic
      regression (MLR) models. The remaining 30% (n: 204) were employed in a holdout
      sample to test the performance of the decision tree and MLR models. Predictive
      performance of different models was analyzed by the receiver operating
      characteristic (ROC) curve using the testing set. Independent variables were
      selected from demographic characteristics and history of drug use. RESULTS: For
      the decision tree model, the sensitivity and specificity for identifying people
      at risk for drug abuse were 66% and 75%, respectively, while the MLR model was
      somewhat less effective at 60% and 73%. Key independent variables in the analyses
      included first substance experience, age at first drug use, age, place of
      residence, history of cigarette use, and occupational and marital status.
      DISCUSSION AND CONCLUSION: While study findings are exploratory and lack
      generalizability they do suggest that the decision tree model holds promise as an
      effective classification approach for identifying risk factors for drug use.
      Convergent with prior research in Western contexts is that age of drug use
      initiation was a critical factor predicting a substance use disorder.

PMID- 29172872
TI  - Ultrasonography in the diagnosis and management of cats with ureteral
      obstruction.
AB  - Objectives The objective was to identify clinical or ultrasonographic results
      associated with ureteral obstruction or outcome in cats with azotaemia. Methods
      This was a retrospective cross-sectional study of cats with azotaemia (serum
      creatinine >180 MUmol/l) that had ultrasonography of the urinary tract,
      ultrasound images available for review and received treatment for azotaemia. Cats
      with pre-renal azotaemia or urethral obstruction were excluded. Associations
      between clinical and ultrasonographic results and the dependent variables
      'tentative diagnosis of ureteral obstruction', 'pyelography positive for ureteral
      obstruction' and 'death in hospital' were tested using binary logistic
      regression. Results In total, 238 cats satisfied the inclusion criteria. Median
      age was 7 years (range 2 weeks to 20 years), duration of clinical signs was 7
      days (range 1 day to 6.3 years) and serum creatinine was 417 MUmol/l (range 184
      2100 MUmol/l). Tentative diagnosis of ureteral obstruction in 92/238 (39%) cats
      was significantly associated with unilateral enlarged kidney on palpation, and
      dilated renal pelvis and calculi within the ureter on ultrasonography.
      Pyelography was performed in 49/92 (53%) cats (16 bilateral) with a tentative
      diagnosis of ureteral obstruction, and was positive for obstruction in 46/65
      (71%) instances. No significant differences in ultrasonographic signs were found
      between cats with obstructed and non-obstructed ureters. Receiver-operating
      characteristic analysis of renal pelvic diameter as a diagnostic test for
      ureteral obstruction found an area under the curve not significantly different
      from 0.5. There was good agreement between results of radiography and
      ultrasonography for presence of urinary calculi (kappa 0.67). Treatment was
      medical in 171 (72%) cats and surgical (ureteral stent or by-pass device) in 67
      (28%). Death in hospital was significantly associated with serum creatinine and
      presence of peritoneal fluid, but not with clinical diagnosis, ultrasonographic
      signs or treatment method. Conclusions and relevance Ultrasonography may be used
      to identify azotaemic cats at greatest risk of ureteral obstruction, but when
      using pyelography as the reference test ultrasonography appears to be inaccurate
      for diagnosis of ureteral obstruction.

PMID- 29172871
TI  - Repeated Measures Analysis of Alcohol Patterns among Gay and Bisexual Men in the
      Momentum Health Study.
AB  - BACKGROUND: This study analyzed repeated study visits (n = 2,624) of 693 gay and
      bisexual men (GBM) in the Momentum Health Study from July, 2012 to June, 2015.
      Based on recent cross-sectional analyses, we hypothesized that over the study
      period: (1) hazardous drinking levels would remain high, (2) GBM classified as
      Hazardous Drinkers will be consistently associated with high risk sex, and (3)
      GBM classified as Always Hazardous Drinkers differ significantly from Sometimes
      Hazardous Drinkers. METHODS: AUDIT classified participants as Non-Hazardous
      Drinkers or Hazardous Drinkers, the Cochran-Mantel-Haenszel Test assessed
      hazardous drinking trends, and Generalized Estimating Equations (GEE) analysis
      identified Hazardous Drinking covariates. Logistic regression analysis of
      participants with at least two study visits (575) compared those who were
      Sometimes Hazardous Drinkers (n = 171) with Always Hazardous Drinkers (n = 129).
      RESULTS: At baseline 40% of participants were Hazardous Drinkers, but there was a
      significant decline in hazardous drinking by visit and Hazardous Drinkers were
      not significantly associated with high risk sex. Always Hazardous Drinkers had
      significantly more high risk sex and gay bar attendance, but less often sought
      Internet sex partners compared to Sometimes Hazardous Drinkers. CONCLUSIONS:
      Analyses did not support the first two hypotheses, but distinguishing between
      Always and Sometimes Hazardous drinkers identified a young GBM subgroup
      associated with significantly higher levels of high risk sex and social support
      measures. These results suggest interventions programs based on Social Norms
      Theory, which predicts peer norms among youth are important factors in regulating
      drinking patterns, may be effective for these men.

PMID- 29172873
TI  - Retrospective evaluation of toceranib phosphate (Palladia) use in cats with mast
      cell neoplasia.
AB  - Objectives The purpose of this study was to solicit and compile data from
      practicing veterinary specialists regarding their use of toceranib in cats with
      mast cell neoplasia and to provide initial assessment of possible clinical
      benefit and adverse events. Methods The American College of Veterinary Internal
      Medicine and Oncology listservs were used to solicit data pertaining to cases in
      which toceranib was used in the treatment of feline mast cell neoplasia. Cases
      were included if the following data were received: signalment (age, sex, breed),
      diagnosis of mast cell neoplasia by either cytology or histopathology, anatomic
      classification of disease (cutaneous, splenic/hepatic, gastrointestinal, other),
      previous and concurrent treatment, toceranib dose (mg/kg) and schedule, duration
      of therapy, best response and documentation of adverse events. Results Case data
      from 50 cats with cutaneous (n = 22), splenic/hepatic (visceral) (n = 10),
      gastrointestinal (n = 17) or other (n = 1) mast cell neoplasia were received.
      Clinical benefit was seen in 80% (40/50), including 86% (19/22) with cutaneous,
      80% (8/10) with visceral and 76% (13/17) with gastrointestinal involvement. A
      majority of cats (n = 35) received glucocorticoids during toceranib treatment.
      Median duration of treatment in cats experiencing clinical benefit was 36 weeks
      (range 4-106 weeks), 48 weeks (range 12-199 weeks) and 23 weeks (range 13-81
      weeks) for cutaneous, visceral and gastrointestinal cases, respectively.
      Toceranib was administered at a median dose of 2.5 mg/kg (range 1.6-3.5 mg/kg);
      in 90% (45/50) the drug was given three times per week. Treatment was generally
      well tolerated with 60% (30/50) of cats experiencing adverse events. The majority
      of these events were low-grade (grade 1 or 2) gastrointestinal or hematologic
      events that resolved with treatment break and/or dose adjustment. Conclusions and
      relevance Toceranib appears to be well tolerated in feline patients with mast
      cell neoplasia. Biologic activity of this drug is evident in the studied cats;
      however, further prospective studies are needed to elucidate fully its role in
      treatment of this disease.

PMID- 29172875
TI  - Consider the eye in preventive healthcare - ocular findings, intraocular pressure
      and Schirmer tear test in ageing cats.
AB  - OBJECTIVES: Geriatric health screening in cats is highly recommended. However,
      information about normal and abnormal findings is scarce, especially regarding
      the eyes of ageing cats. This prospective study examined the influence of the
      ageing process on vision and ocular structures in older cats. METHODS: A total of
      209 cats (aged 9-24 years) underwent physical examination, vision assessment,
      slit lamp biomicroscopy and ophthalmoscopy. Systolic blood pressure (SBP)
      measurement, Schirmer tear test (STT) reading and rebound tonometry were
      performed. Systemic disease was not a criterion for exclusion. RESULTS: Vision
      was good in 157/209 cats (75.1%) and impaired in 52/209 cats (24.9%). Increasing
      age and the occurrence of vision impairment were not statistically associated ( P
      = 0.053). Retinal oedema, retinal haemorrhage and/or retinal detachment (19 cats)
      and glaucoma (12 cats) were the most common findings in vision impaired cats.
      Increasing age was significantly associated with the occurrence of lenticular
      sclerosis ( P = 0.01) and attenuated retinal vessels ( P = 0.02). Increasing age
      and SBP were significantly associated with the occurrence of retinal detachment,
      haemorrhage and oedema ( P <0.001 each). In cats without evidence of hypertensive
      ocular damage, younger cats had a tendency for higher SBP values than older cats,
      although this difference was not significant. Mean intraocular pressure (IOP) was
      16.5 +/- 5.0 mmHg. Age did not significantly affect the IOP values ( P = 0.54).
      Mean STT was 15.8 +/- 4.8 mm/min. The STT was found to increase with age ( P =
      0.025). CONCLUSIONS AND RELEVANCE: Although vision impairment is not a clinical
      sign of old age in cats, age-related changes may contribute to vision-threatening
      diseases. This study contributes to preventive healthcare by examining the
      influence of the ageing process on vision and ocular structures in older cats.

PMID- 29172874
TI  - Nfia deletion in myeloid cells blocks expansion of myeloid-derived suppressor
      cells during sepsis.
AB  - Sepsis-induced immunosuppression increases the risk of chronic infection and
      reduces survival. Myeloid-derived suppressor cells (MDSCs) expand in the bone
      marrow and spleen during murine polymicrobial sepsis, contributing to
      immunosuppression. A better understanding of molecular controls of MDSC
      production is needed to identify treatment targets. We previously reported that
      miR-21 and miR-181b couple with transcription factor NFI-A to induce MDSCs during
      murine sepsis. Here, we expand upon these observations by showing that
      conditional deletion of the Nfia gene in the myeloid lineage precludes MDSC
      development. NFI-A-deficient Gr1+CD11b+ myeloid cells are not immunosuppressive
      and differentiate normally into macrophages and dendritic cells. In contrast,
      ectopically expressed NFI-A prevents differentiation of these immature Gr1+CD11b+
      cells, while converting them into MDSCs. In addition, NFI-A-deficient Gr1+CD11b+
      cells decreased, and cells transfected with NFI-A increase expression of miR-21
      and miR181b. Our results support a myeloid cell loop in which NFI-A and miR-21
      and miR-181b sustain Gr1+CD11b+ MDSC-dependent immunosuppression during sepsis.

PMID- 29172876
TI  - Limbal Stem Cell Transplantation and Complications.
AB  - Corneal epithelial stem cells are adult somatic stem cells located at the limbus
      and represent the ultimate source of transparent corneal epithelium. When these
      limbal stem cells become dysfunctional or deficient, limbal stem cell deficiency
      (LSCD) develops. LSCD is a major cause of corneal scarring and is particularly
      prevalent in chemical and thermal burns of the ocular surface. LSCD leads to
      conjunctivalization of the corneal surface, neovascularization, recurrent or
      persistent epithelial defects, ocular surface inflammation, and scarring that, in
      turn, lead to decreased vision, pain, and impaired quality of life. Several
      techniques have been reported for limbal stem cell transplantation (LSCT). We
      introduce the surgical techniques, examine the success rate, and discuss the
      postoperative complications of conjunctival limbal autograft (CLAU), cultivated
      limbal stem cell transplantation (CLET), simple limbal epithelial transplantation
      (SLET), and limbal allograft, including keratolimbal allografts (KLAL) and living
      related conjunctival allograft (LR-CLAL).

PMID- 29172877
TI  - Frequent Drug Use and Negative Employment Outcomes among the Criminally Active.
AB  - BACKGROUND: Employment is a central component of economic independence and is
      widely viewed as an essential element of social control. Whether frequent drug
      use reduces the likelihood of employment or obstructs hours worked, wages, and
      job commitment is therefore an important question about which there remains
      uncertainty. METHODS: We improve on shortcomings of prior research through a
      monthly within-person analysis of a population at high-risk of both drug use and
      poor employment outcomes. We present multilevel models of the 18 months spent on
      the street preceding the arrest that led to incarceration in minimum/medium
      security facilities in Ohio from a random sample of 250 adult male inmates
      interviewed during the outset of a prison spell. RESULTS: The analysis reveals
      consistently strong, negative effects of frequent drug use on employment, hours
      worked, and wages in the month following frequent drug use, including marijuana,
      cocaine, heroin, and prescription opioids. As well, frequent drug use (with the
      exception of marijuana) undermines job commitment during the months that
      participants are employed. CONCLUSIONS: The consequences of frequent drug use for
      future employment are consistently negative within this criminal justice sample.
      Results suggest that lower levels of drug use may improve the success of
      postrelease employment programs. In a context of increasing concern over rising
      opioid and heroin, but also cocaine and marijuana abuse, the findings suggest a
      renewed focus on and perhaps expansion of evidence-based drug treatment among
      populations embedded within the criminal justice system, particularly if
      employment constrains criminal behavior.

PMID- 29172878
TI  - The economic evidence for advanced imaging in the diagnosis of suspected scaphoid
      fractures: systematic review of evidence.
AB  - Given the limitations of conventional radiography in the diagnosis of suspected
      scaphoid fractures on presentation, advanced imaging, particularly magnetic
      resonance imaging, is a useful additional investigation. We carried out a
      systematic review of the economic evidence for the use of advanced imaging in the
      management of suspected scaphoid fractures. Fifteen articles were included in the
      review. Owing to the heterogeneity of study designs, the type and timing of
      interventions and the economic analyses performed, direct comparisons between the
      15 studies were difficult. From a health care perspective, little could be
      concluded regarding the economic implications of the use of advanced imaging in
      clinical practice. However, from a societal perspective, the evidence favours the
      use of advanced imaging in the management of suspected scaphoid fractures as it
      does appear to lead to overall cost-savings.

PMID- 29172879
TI  - Circadian Rhythms in Visual Responsiveness in the Behaviorally Arrhythmic
      Drosophila Clock Mutant ClkJrk.
AB  - An organism's biological day is characterized by a pattern of anticipatory
      physiological and behavioral changes that are governed by circadian clocks to
      align with the 24-h cycling environment. Here, we used flash electroretinograms
      (ERGs) and steady-state visually evoked potentials (SSVEPs) to examine how visual
      responsiveness in wild-type Drosophila melanogaster and the circadian clock
      mutant ClkJrk varies over circadian time. We show that the ERG parameters of wild
      type flies vary over the circadian day, with a higher luminance response during
      the subjective night. The SSVEP response that assesses contrast sensitivity also
      showed a time-of-day dependence, including 2 prominent peaks within a 24-h period
      and a maximal response at the end of the subjective day, indicating a tradeoff
      between luminance and contrast sensitivity. Moreover, the behaviorally arrhythmic
      ClkJrk mutants maintained a circadian profile in both luminance and contrast
      sensitivity, but unlike the wild-types, which show bimodal profiles in their
      visual response, ClkJrk flies show a weakening of the bimodal character, with
      visual responsiveness tending to peak once a day. We conclude that the ClkJrk
      mutation mainly affects 1 of 2 functionally coupled oscillators and that the
      visual system is partially separated from the locomotor circadian circuits that
      drive bouts of morning and evening activity. As light exposure is a major
      mechanism for entrainment, our work suggests that a detailed temporal analysis of
      electrophysiological responses is warranted to better identify the time window at
      which circadian rhythms are most receptive to light-induced phase shifting.

PMID- 29172880
TI  - Spiritual Struggles and Problem Drinking: Are Younger Adults at Greater Risk than
      Older Adults?
AB  - BACKGROUND: Although a good deal of research has assessed the positive effects
      that involvement in religion has on alcohol use, there is relatively little
      research on the negative aspects of religious life and alcohol problems.
      OBJECTIVES: This study has two objectives. The first is to see if spiritual
      struggles are associated with problem drinking. The second is to see if the
      relationship between spiritual struggles and problem drinking is stronger for
      younger than for older adults. METHODS: The data come from a recent nationwide
      survey of adults of all ages who reside in the United States (N = 2142).The study
      was conducted in 2014. Problem drinking is assessed with the CAGE questionnaire.
      RESULTS: The findings indicate that people who encounter more spiritual struggles
      are more likely to experience problem drinking. The relationship between
      spiritual struggles and problem drinking was stronger than the relationship
      between three other frequently used measures of religion and problem drinking
      (i.e., attendance at worship services, private prayer, and affiliation with
      Evangelical denominations). The results further reveal that spiritual struggles
      are associated with a greater risk of drinking problems among younger than among
      older individuals. Conclusions/Importance: Although many studies show that
      various facets of religion are associated with a lower risk of experiencing
      problems with alcohol the findings from the current study show that there are
      negative aspects of religious life that may be associated with a greater risk of
      having problems with alcohol.

PMID- 29172881
TI  - The Institute of Medicine recommendation for gestational weight gain is probably
      not optimal among non-American pregnant women: a retrospective study from China.
AB  - PURPOSE: To investigate whether the Institute of Medicine (IOM) recommended
      gestational weight gain (GWG) range is optimal among Chinese singleton pregnant
      women. METHODS: For the purpose of a retrospective observational study, data on
      8209 mature singleton deliveries in Shanghai from January 2014 to December 2016
      were extracted from medical records in terms of clinical performance. All cases
      were categorized as undergainers, appropriate-gainers, and above-gainers
      according to IOM recommended gestational weight gain range after stratification
      of maternal BMI and proportions of three categories were calculated. Comparisons
      of maternal and neonatal outcome were conducted among three categories and the
      associations of those outcome including risks of low birth weight (LBW) and
      macrosomia (MAC) with GWG were estimated by logistic regression analysis. To
      examine the applicability of IOM recommendation for Chinese pregnant women, the
      accumulated risk of LBW and MAC was displayed by stacked column chart and
      comparison was made among GWG category. The joint predicted risk (JPR) curve of
      both LBW and MAC in relation to GWG (continuous measurement) was plotted to
      demonstrate the relation of lowest JPR corresponding GWG with IOM range. RESULTS:
      The IOM recommended weight gain was achieved only by 3502 (42.7%) pregnant women
      and 41.6% gained excessive weight during pregnancy, especially for the overweight
      and obese women, the proportions of above-gainers mounting to 65.7 and 75.9%,
      respectively. By multivariate analysis GWG significantly influenced the risk of
      MAC and caesarean section. Although the association between the risk of LBW and
      GWG was not significant, p value reached .051. The risk of delivering macrosomia
      and caesarean section doubled when GWG exceeded the IOM rang. Appropriate gainers
      did not always gain the lowest joint risk of low birth weight and macrosomia from
      stacked column chart and it is obvious that the GWG point according to the lowest
      JPR was always located left to the IOM recommended range for each BMI category
      from the JPR curve chart in relation to GWG. CONCLUSIONS: The IOM recommended GWG
      range is possibly too much for Chinese singleton pregnant population for each BMI
      category. It is necessary to build different gestational weight gain standards
      for specific ethnic population.

PMID- 29172882
TI  - Feeding Vitamin C during Neonatal and Juvenile Growth Improves Learning and
      Memory of Rats.
AB  - We investigated the effects of feeding vitamin C (Vit C) during neonatal and
      juvenile growth on learning and memory of rats. Rats after delivery were randomly
      divided into four groups and treated. Group 1, control group, received normal
      drinking water. Groups 2-4 received Vit C 10, 100, and 500 mg/kg, respectively,
      from the first day. After 8 weeks, 10 male offspring of each group were randomly
      selected and tested in the Morris water maze (MWM) and passive avoidance (PA)
      tests. Finally, the brains were removed for biochemical measurement. In MWM, 10
      500 mg/kg Vit C reduced the latency and traveled distance and increased time
      spent in the target quadrant. In PA, 10 and 100 mg/kg of Vit C increased the
      latency; 10-500 mg/kg of Vit C decreased the malondialdehyde (MDA) in the brain
      tissues and increased thiol and catalase (CAT) activity compared to the control
      group. We showed that feeding rats Vit C during neonatal and juvenile growth has
      positive effects on learning and memory.

PMID- 29172883
TI  - Prevalence & correlates of chronic perinatal pain - a study from India.
AB  - OBJECTIVES: To study the prevalence of chronic perinatal pain among mothers who
      had infants between the ages of 13-25 months in the State of Kerala, India and to
      report its correlates in the socio-demographic, obstetric and psychological
      domains. METHODS: A total of 9305 mothers selected by cluster random sampling
      were assessed cross-sectionally for chronic perinatal pain using a questionnaire
      by Junior Public Health Nurses (JPHNs). In addition, information regarding socio
      demographic profile, obstetric history, infant details and perinatal depression
      were collected. RESULTS: Of the 8302 (89.3%) valid responses, 552 (6.6%) mothers
      reported chronic perinatal pain. Among those with pain, 142 (25.6%) reported pain
      during pregnancy, 314 (56.7%) during postpartum and 96 (17.7%) during both
      periods. The commonest sites of pain reported were back 280 (51%) and pelvic
      region 110 (19%). Mothers with chronic perinatal pain were more likely to be
      younger, less educated, employed and from an urban background. Chronic perinatal
      pain was associated with obstetric complications, delivery by
      instrumental/caesarean section, non-exclusive breast feeding and higher maternal
      depression scores. CONCLUSION: Chronic pain is common among mothers in India
      during the perinatal period and greater attention needs to be given for it to be
      recognised and treated early.

PMID- 29172884
TI  - Social technology: helping or hindering communication in care?

PMID- 29172885
TI  - What influences palliative care nurses in their choice to engage in or decline
      clinical supervision?
AB  - BACKGROUND: Clinical supervision (CS) has been around since the early 1990s in
      the UK and has been endorsed by government and professional bodies. Levels of
      engagement range from 18% to 85%. AIM: To investigate what influences palliative
      care nurses in their choice to engage in or decline clinical supervision. METHOD:
      A qualitative study was undertaken in an inpatient hospice in England and
      employed two focus groups to compare the views of participants and non
      participants in CS. Data were audio recorded and transcribed verbatim by the
      researchers and analysed using systematic text condensation. FINDINGS: Palliative
      care nurses all used informal team support for 'in the moment' support. Some
      engaged in formal CS to reflect 'on action' and to challenge practice. Nurses
      reported a lack of clarity regarding CS but, once this was overcome and
      engagement with CS was established, it led to changes in practice, identification
      of training needs and team building. The option of choice between group and
      individual supervision was found to be important. Group supervision led to
      enhanced understanding of group members which also led to team building,
      individual sessions were useful for individual issues. Protected time was
      essential for staff to be able to engage in CS. Staff who worked in larger teams
      reported higher levels of engagement, whereas a small team reported less need due
      to more informal team support. CONCLUSION: These findings are positive as they
      illuminate the importance of choice for support. Nurses need to be aware of their
      options for support and ultimately how this support affects the care they
      provide. The Palliative Care Nurse's Model of Support was developed, which shows
      the effects of each choice and how this may lead to team-building.

PMID- 29172886
TI  - Research roundup.
AB  - Synopses of a selection of recently published research articles of relevance to
      palliative care.

PMID- 29172887
TI  - Predicting hospital transfers among nursing home residents in the last months of
      life.
AB  - BACKGROUND: Concerns have been raised over the practice of transferring nursing
      home residents to hospital at their end of life. OBJECTIVE: To examine the family
      and facility factors that may influence the decision to transfer nursing home
      residents to hospital in the last month of life. RESEARCH DESIGN: Secondary data
      analysis includes a sample of 119 bereaved family members from 21 nursing homes
      located in Central Canada. METHOD: A binary logistic regression analysis was
      conducted to explore the predictors for hospital transfers. RESULTS: Terminal
      hospital transfers were common: 70% of nursing home residents were sent to
      hospitals in the last month of their life, and the likelihood of terminal
      hospital transfers increased by having an adult child as decision-maker (odds
      ratio (OR) = 5.03; 95% confidence interval (CI) = 1.6, 16; significance
      level/probability value (p) = 0.007) or having a lower family income (OR = 2.9;
      95% CI =1.1, 2.9; p = 0.027). Discussion and implications: The identified
      predictors for terminal hospital transfers are helpful in targeting and
      developing interventions to improve end-of-life care. Particular emphasis should
      therefore be placed on targeting families with low income and children of the
      nursing home residents for educational initiatives such as advance care planning
      awareness, in order to prevent terminal hospital transfers. It is hoped that
      policy-makers and practitioners can start addressing the findings of this study
      to reduce terminal hospital transfers at end of life and promote quality end-of
      life care in nursing homes.

PMID- 29172888
TI  - Corrigendum.

PMID- 29172889
TI  - Communication disorders in palliative care: investigating the views, attitudes
      and beliefs of speech and language therapists.
AB  - AIM: Speech and language therapists (SLTs) provide intervention for communication
      and swallowing to patients with life-limiting conditions, such as dementia and
      head and neck cancer. The role of the SLT in palliative care is difficult to
      define. Much is known about the clinical aspects of this role; however, little is
      known about the core values, beliefs and expectations of SLTs working in this
      sector, particularly with regard to their role in supporting patients'
      communication. Through a series of semi-structured interviews and a follow-up
      focus group, this report aimed to form a picture of the experiences and views of
      SLTs about their communication role in palliative care. Results suggest that SLTs
      are forging a self-identity in a sector that is itself constantly evolving, which
      causes difficulties in defining their role. Participants report that other health
      professionals have a poor understanding of the SLT's role. SLTs may benefit from
      palliative care-specific guidelines and increased interprofessional awareness of
      their role in order to become better integrated into the palliative care sector.

PMID- 29172890
TI  - Challenges to advance care planning among multidisciplinary health professionals
      in China.
AB  - BACKGROUND: Advance care planning (ACP) is a critical component of quality end-of
      life care. Little is known regarding the cultural influences on health
      professionals' attitudes toward the discussion of ACP in China. OBJECTIVE: To
      better understand attitudes toward ACP among Chinese healthcare professionals in
      China and the influence of cultural factors such as filial piety, or xiao.
      METHODS: A mixed methods study was used. This study reports the results of a
      descriptive cross-sectional survey of physicians, nurses and social workers with
      experience in palliative and end-of-life care. RESULTS: Some 102 completed
      surveys were obtained. Most Chinese health professionals had an overall positive
      attitude toward ACP, acknowledging that these discussions should occur. However,
      there was a general lack of confidence and sense of reluctance among participants
      to engage in ACP discussions. CONCLUSION: The lack of statistical difference
      between the various health professionals suggests that they all faced challenges
      in participating in ACP discussions. Future research should focus on the
      influences of cultural factors such as xiao on ACP discussion, and develop
      culturally sensitive strategies to facilitate these discussions in the Chinese
      community.

PMID- 29172891
TI  - Politics and palliative care: Central African Republic.
AB  - Dion Smyth's review of palliative nursing on the internet.

PMID- 29172892
TI  - Attitudes of nurses towards care of the dying patient in India.
AB  - BACKGROUND: Worldwide, end-of-life care is coming under increasing scrutiny as
      nurses struggle to balance cultural norms and legal requirements with the desires
      of patients and families. The purpose of this descriptive pilot study was to
      examine and describe nurses' attitudes when caring for dying patients in India,
      and whether participation in an educational conference, which included two
      scenario-based, low-fidelity simulations increased knowledge of end-of-life care.
      METHOD: Participants' attitudes were measured with the 30-item Frommelt Attitudes
      Toward Care of the Dying (FATCOD-B) scale. Knowledge was measured with a
      researcher-developed 15-item content-focused test before and after the
      conference. RESULTS: The mean attitude scores of nurses (n=101) were M=101.45
      (range 65-143, SD=15.99). Participation in the educational conference and end-of
      life care simulations increased the knowledge of most nurses (P<0.05).
      CONCLUSION: Conferences and low-fidelity simulation are effective methods for
      improving nurses' knowledge of end-of-life care in India. Improved education
      surrounding end of life may positively affect attitudes.

PMID- 29172893
TI  - Effect of age, sex and body weight on the serum concentrations of cobalamin and
      folate in cats consuming a consistent diet.
AB  - Objectives Multiple feline diseases involving the gastrointestinal tract,
      pancreas, liver and biliary tract are known to cause abnormal serum cobalamin and
      folate concentrations. Measuring the serum concentration of these vitamins can
      therefore be a helpful diagnostic tool. However, factors other than disease, in
      particular age, have also been suggested to have an effect on the serum
      concentration of cobalamin and folate. In previous studies, the dietary intake
      was not standardised, or even known, despite diet being the prinicpal source of
      both vitamins. Therefore, we evaluated the effect of age, sex and body weight on
      the serum concentration of folate and cobalamin in cats fed the same diet.
      Methods The serum cobalamin and folate concentrations were measured in 65
      apparently healthy cats in a nutrition colony that had been fed an identical
      diet. A linear model was used to test the relationship between the serum
      concentration of cobalamin and folate with the variables age, sex and body
      weight. Results There was a large variation in the serum concentration of both
      folate and cobalamin, despite identical intake. Serum cobalamin was inversely
      associated with age ( P = 0.002), and males had higher concentrations than
      females ( P = 0.039). Serum folate was positively associated with age ( P =
      0.01). Conclusions and relevance Independent of diet, serum cobalamin
      concentration decreases with age. Changes in gastrointestinal function,
      microflora or metabolism may be responsible. Older cats may be more susceptible
      to cobalamin deficiency secondary to inappetence or gastrointestinal disease.

PMID- 29172894
TI  - A Woman's Right to Dignified, Respectful Healthcare During Childbirth: A Review
      of the Literature on Obstetric Mistreatment.

PMID- 29172895
TI  - Optimal gain control step sizes for bimodal stimulation.
AB  - OBJECTIVE: Cochlear implants (CI) and hearing aids (HA) have a gain control that
      allows the bimodal user to change the loudness. Due to differences in dynamic
      range between CI and HA, an equal change of the gains of the two devices results
      in different changes in loudness. The objective was to relate and individualise
      the step sizes of the loudness controls to obtain a similar perceptual effect in
      the two ears. DESIGN: We used loudness models parametrised for individual users
      to find a relation between the controls of the CI and the HA such that each step
      resulted in an equal change in loudness. We conducted loudness balancing
      experiments to validate the results. STUDY SAMPLE: Eleven bimodal users of whom
      six were tested in a prior study. RESULTS: The difference between the optimal
      gain from the loudness balancing procedure and actual gain was 3.3 dB when the
      new relation was applied. In contrast, the difference was 8 dB if equal step
      sized were applied at both sides. CONCLUSION: We can relate the controls such
      that each step results in a similar loudness difference.

PMID- 29172896
TI  - Tai Chi for Posttraumatic Stress Disorder and Chronic Musculoskeletal Pain: A
      Pilot Study.
AB  - PURPOSE: Explore the feasibility of a Tai Chi intervention to improve
      musculoskeletal pain, emotion, cognition, and physical function in individuals
      with posttraumatic stress disorder. DESIGN: Two-phase, one-arm quasi-experimental
      design. METHOD: Phase 1: 11 participants completed one Tai Chi session,
      feasibility questionnaire, and were offered participation in Phase 2, a 12-week
      Tai Chi intervention. Ten participants participated in Phase 2. Pain intensity,
      interference, physical function scales, an emotional battery, and cognition tests
      were used for pre- and postintervention outcome measures. Paired t tests and
      thematic analysis were used for analysis. FINDINGS: In Phase 1, most felt Tai Chi
      would benefit health (90.9%) and expressed interest in continuing Tai Chi (6.73
      out of 7). Phase 2 results showed improvement in fear-affect (raw t = -2.64, p =
      .03; age adjusted t = -2.90, p = .02), fear-somatic arousal (raw t = -2.53, p =
      .035), List Sorting Working Memory (raw t = 2.62, p = .031; age adjusted t =
      2.96, p = .018), 6-Minute Walk Test ( t = 3.541, p = .008), and current level of
      Pain Intensity ( t = -4.00, p = .004). CONCLUSIONS: Tai Chi is an acceptable,
      holistic treatment to individuals with musculoskeletal pain and posttraumatic
      stress disorder. It may reduce pain, improve emotion, memory, and physical
      function.

PMID- 29172897
TI  - Tied to the worldly work of writing: Parent as ethnographer.
AB  - Parent narratives have contributed to ethnographic accounts of the lives of
      children with autism, but there are fewer examples of parents producing their own
      autoethnographies. This article explores the affordances of an online blog for
      enabling a parent of a child with autism to produce a written record of practice
      which may be considered 'autoethnographic'. Richardson's framework for
      ethnography as Creative Analytic Process (CAP) is applied to extracts from a blog
      post in order to consider its contribution, reflexivity, aesthetic merit and
      impact. The article addresses the methodological and ethical implications of
      reconceptualizing parents as researchers and the potential contribution of new
      writing platforms to the development of auto/ethnography.

PMID- 29172898
TI  - Mitochondrial genome mutations in 13 subunits of respiratory chain complexes in
      Chinese Han and Mongolian hypertensive individuals.
AB  - Mitochondrial DNA (mtDNA) mutations are associated with cardiovascular disease,
      including hypertension (HTN). Here we performed a genetic and molecular analysis
      of 13 mtDNA-encoded subunits of respiratory chain complexes in 100 Chinese Han
      and 80 Mongolian HTN cases, and 100 Han and 42 Mongolian normotension subjects.
      The total cholesterol of the Mongolian normotensive subjects was higher than that
      of the Han normotensive group (p < .05). Sequence analysis identified 636 point
      mutations in the 13 mtDNA-encoded subunits in the Han and Mongolian hypertensive
      individuals, including 66 in NADH dehydrogenase subunit 1(ND1), 62 in ND2, 71 in
      COI, 29 in COII, 17 in ATP8, one in ATP6/8, 49 in ATP6, 27 in COIII, 27 in ND3,
      14 in ND4L, 74 in ND4, 97 in ND5, 24 in ND6, and 78 in CYTB. Eight of these point
      mutations were present at significantly different frequencies in Han and
      Mongolian hypertensive individuals. Thirty-one point mutations were present only
      in Mongolian hypertensive individuals, while 73 were present only in Han
      hypertensive individuals. The relation between point mutations in 13 mtDNA
      encoded subunits of respiratory chain complexes and HTN is worth to further
      research in future; however, the functional effects of these mutations require
      elucidation.

PMID- 29172899
TI  - How does feedback from patients impact upon healthcare student clinical skill
      development and learning? A systematic review.
AB  - BACKGROUND: A key feature of health professionals' training, irrespective of
      discipline, is the acquisition and application of clinical and communication
      skills. Despite this, little is known about the potential role of patient
      feedback on this process. This systematic review aimed to answer the question:
      How does feedback from patients impact upon healthcare student clinical skill
      development and learning? DESIGN: Systematic review of published literature.
      METHODS: Electronic databases were searched for studies that explored the effects
      of patient feedback on student learning and were published before March 2016.
      Eligible articles underwent methodological evaluation using the McMaster
      University Critical Evaluation Forms and data extraction. RESULTS: A total of 237
      articles were retrieved following searches of electronic databases and hand
      searches of reference lists. Twelve (7 quantitative, 2 qualitative, 3 mixed
      methods) studies met the inclusion criteria. Eleven studies reported that patient
      feedback improved students' clinical skills. CONCLUSION: Minimal research has
      explored the impact of patient feedback on student learning. The research to date
      suggests that direct feedback from patients may be beneficial for the development
      of students' communication and clinical skills; however, the wide variety of
      evaluation methods and the lack of validated tools for patients to provide
      feedback suggest that further exploration is warranted.

PMID- 29172901
TI  - Correction to: J Med Food 2017;20:1113-1120. DOI: 10.1089/jmf.2017.3951.

PMID- 29172902
TI  - Insulin-like growth factor type 1 concentrations in hyperthyroid cats before and
      after treatment with thiamazole.
AB  - Objectives The aim of this study was to evaluate changes in circulating insulin
      like growth factor type 1 (IGF-1) concentrations in hyperthyroid cats, before and
      after thiamazole treatment. Methods Thirty-four hyperthyroid cats were
      retrospectively included. Plasma free thyroxine (fT4) and IGF-1 concentrations
      were measured at diagnosis and 3 months after initiating antithyroid drug
      therapy. Results Median fT4 significantly decreased ( P <0.001) after treatment
      (from 78 pmol/l [range 43-122 pmol/l] to 31 pmol/l [range below assay limit of
      detection to 88 pmol/l]), whereas IGF-1 values significantly increased ( P
      <0.001) after treatment (from 117 ng/ml [33-341 ng/ml] to 221 ng/ml [36-865
      ng/ml]). fT4 and IGF-1 concentrations were significantly negatively correlated
      both at diagnosis (r = -0.43, P = 0.01) and after treatment (r = -0.51, P =
      0.002). Conclusions and relevance In cats, IGF-1 concentrations appear to be
      inversely proportional to the severity of hyperthyroidism and significantly
      increase after treatment with thiamazole.

PMID- 29172900
TI  - Development of a high-yield expression and purification system for platelet
      factor 4.
AB  - Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction characterized
      by IgG antibodies bound to complexes of platelet factor 4 (PF4) and heparin. The
      majority of diagnostic tests for HIT rely on an exogenous source of PF4 to
      identify anti-PF4/heparin antibodies. These include the PF4-dependent enhanced
      serotonin release assay (PF4-SRA) among others. Using a bacterial expression
      system, we developed a novel and efficient method of producing recombinant human
      PF4 (rhPF4) that is biochemically and antigenically similar to platelet-derived
      human PF4. rhPF4 was produced using the pET expression system in the BL21(DE3)
      strain of Escherichia coli. The system was optimized for protein expression using
      isopropyl beta-D-1-thiogalactopyranoside at different induction temperatures and
      incubation times. rhPF4 solubility was improved by using different detergents
      during cell lysis and by purifying with heparin affinity and ion exchange
      chromatography. Biochemical characteristics of rhPF4 were investigated using mass
      spectrometry, SDS-PAGE analysis, and gel filtration chromatography and compared
      to platelet-derived PF4. Antigenic and functional characteristics of rhPF4 were
      studied using the anti-PF4/heparin EIA and the PF4-SRA. Using this method, we
      could produce 11.4 +/- 0.6 mg of pure rhPF4 per liter of bacterial culture.
      Absorbance readings from the anti-PF4/heparin EIA using platelet-derived and
      rhPF4 were highly correlated (n = 194; r = 0.9545, p < 0.0001); and functional
      release of serotonin in the PF4-SRA induced by anti-PF4/heparin antibodies was
      similar to either platelet-derived or rhPF4 and heparin (r = 0.9597, p < 0.0001).
      Our method of rhPF4 production is efficient and does not rely on a source of
      platelets. The rhPF4 purification method described produces greater yields at a
      lower cost than other current methods. The application of this method can improve
      the efficiency of biochemical investigations and HIT diagnostic testing by
      supplying sufficient amounts of PF4.

PMID- 29172903
TI  - Self-Care for Nurse Leaders in Acute Care Environment Reduces Perceived Stress: A
      Mixed-Methods Pilot Study Merits Further Investigation.
AB  - Acute care practice settings are stressful. Nurse leaders face stressful demands
      of numerous competing priorities. Some nurse leaders experience unmanageable
      stress, but success requires self-care. This article presents a repeated measures
      intervention design study using mixed methods to investigate a self-care simple
      meditation practice for nurse leaders. Themes and subthemes emerged in
      association with the three data collection points: at baseline (pretest), after 6
      weeks, and after 12 weeks (posttest) from introduction of the self-care simple
      meditation practice. An analysis of variance yielded a statistically significant
      drop in perceived stress at 6 weeks and again at 12 weeks. Conducting future
      research is merited.

PMID- 29172904
TI  - The Association Between Past Sexual Abuse and Depression in Older Adults From
      Colombia.
AB  - To explore the association between past sexual abuse and depression in elders
      living in Bogota, Colombia, we used data from the SABE (Salud, Bienestar y
      Envejecimiento [Health, Well-being, and Aging]) Bogota Study. Participants were
      2000 community-dwelling adults aged 60 years and older in 2012. Sexual abuse was
      assessed by self-report. Depression was measured by the Geriatric Depression
      Scale. The weighted prevalence estimate was 2.6% for past sexual abuse and 23.4%
      for depression. Multivariate data analyses showed significantly higher odds of
      depression for past sexual abuse (odds ratio [OR] = 3.91, 95% confidence interval
      [CI]: 2.13-7.16). Other characteristics associated with depression were history
      of being displaced by violence (OR = 1.77, 95% CI: 1.30-2.40), low socioeconomic
      status, low education, poor self-rated health status, and poor self-rated memory.
      Thus, past sexual abuse and history of being displaced by violence were strongly
      associated with depression among Colombian elderly individuals.

PMID- 29172905
TI  - Retrospective study of more than 9000 feline cutaneous tumours in the UK: 2006
      2013.
AB  - Objectives The aim of the study was to utilise a large database available from a
      UK-based, commercial veterinary diagnostic laboratory to ascertain the prevalence
      of different forms of cutaneous neoplasia within the feline population, and to
      detect any breed, sex or age predilections for the more common tumours. Methods
      Records from the laboratory were searched for feline submissions received between
      31 May 2006 and 31 October 2013. For masses arising within the skin for which
      histopathology had been performed, the diagnosis was recorded together with the
      breed, age, sex and neuter status of the cat. Odds ratios for breed
      predisposition to skin tumours overall, to histologically malignant tumours and
      to the more commonly occurring tumours were calculated, with the non-pedigree cat
      population as the control. Results Of the 219,083 feline samples submitted,
      masses arising within the skin comprised 4.4% and there were 89 different
      diagnoses recorded for these masses. Just 6.6% of these cases were non-neoplastic
      in nature, and, of neoplastic masses, 52.7% were considered histologically
      malignant. The 10 most common skin tumour types accounted for 80.7% of cases,
      with the four most common being basal cell tumours, fibrosarcomas, squamous cell
      carcinomas and mast cell tumours. Conclusions and relevance Despite the large
      number of different diagnoses in this study, a relatively small number of tumour
      types accounts for the majority of skin masses occurring in cats, most of which
      are neoplastic in nature. There are a number of breed predispositions for the
      more common tumour types, although no pedigree breed had increased odds of
      developing a malignant tumour compared with the non-pedigree cat population;
      several breeds had significantly decreased odds. Just over half of the neoplastic
      masses in this study were considered histologically malignant.

PMID- 29172906
TI  - Telenursing and Nurse-Patient Communication Within Fertility, Inc.
AB  - The purpose of this study is to examine patient perceptions of practitioner
      patient communication in reproductive endocrinology and infertility (REI)
      practices. During this study, we uncovered the importance of telenursing for
      nurse-patient communication during REI treatment. Telenursing, which is defined
      as the use of wireless technology for out-of-office communication, is the basis
      for out-of-office communication. We examined participants' conceptualization of
      supportive and unsupportive communication, through the lens of biomedicalization
      theory. After conducting 23 interviews, we conclude that telenursing is integral
      to providing holistic nursing care during treatment at REI practices. We discuss
      efficient and effective uses of telenursing and patients' positive perceptions
      telenursing and assess telenursing as both an embrace of and form of resistance
      to biomedicalization within Fertility, Inc. Theoretical and practical
      implications are offered, including suggestions for increasing patient access to
      telenursing while protecting REI nurses from burnout.

PMID- 29172907
TI  - 3 steps to improve reporting and interpretation of patient-reported outcome
      scores in orthopedic studies.

PMID- 29172908
TI  - The Personal and Professional Experiences of Integrative Nurse Coach Certificate
      Program Graduates: A Pilot Study.
AB  - Integrative Nurse Coaching is a new practice in professional nursing. The purpose
      of this pilot study is to describe Integrative Nurse Coach Certificate Program
      graduates' personal and professional experiences. This is a qualitative, pilot
      study with a convenience sample of Integrative Nurse Coach Certificate Program
      graduates ( n = 13). Researchers conducted semistructured interviews and
      identified common themes. The pilot study found four common themes from the
      participants' experiences as follows: (1) development of self, (2) enriched self
      care, (3) a call to action for facilitating the health care paradigm shift, and
      (4) incorporating Integrative Nurse Coaching into practice. The pilot study's
      findings and conclusions provide insight into the potential benefits of
      Integrative Nurse Coaching and the importance of nurse self-care.

PMID- 29172909
TI  - Health Care Utilization Following Vagus Nerve Stimulation Therapy in Pediatric
      Epilepsy Patients From a Pediatric Accountable Care Organization.
AB  - BACKGROUND: Vagus nerve stimulation has been a therapy for epilepsy approved by
      the US Food and Drug Administration (FDA) for patients 4 and older and shown
      efficacy and safety in younger pediatric patients. METHODS: The authors performed
      a retrospective analysis utilizing Medicaid claims from an accountable care
      organization to measure the intervention of vagus nerve stimulation therapy in
      regard to unplanned health care utilization. Thirteen unique patients were
      included who had vagus nerve stimulation therapy who had at least 6 months of
      continuous enrollment in a managed Medicaid health plan. Comparison with 12
      months of data before and after vagus nerve stimulation implantation was
      performed. RESULTS: Patients had statistically significant fewer unplanned
      inpatient visits per patient per enrollment month after vagus nerve stimulation
      implantation. CONCLUSION: Utilizing claims data, vagus nerve stimulation
      implantation demonstrates a reduction in unplanned hospitalizations.

PMID- 29172910
TI  - Comparison of real-time PCR with fungal culture for the diagnosis of Microsporum
      canis dermatophytosis in shelter cats: a field study.
AB  - Objectives Fungal culture requires at least 14 days for a final result, compared
      with 1-3 days for PCR. The study compared a commercial real-time dermatophyte PCR
      panel with fungal culture in cats in a shelter setting for: (1) diagnosis of
      Microsporum canis infection; and (2) determination of mycological cure. Methods
      This was a cross-sectional, observational study of cats with suspicious skin
      lesions or suspected exposure to dermatophytosis. Hair samples were collected for
      fungal culture and PCR prior to treatment and at weekly intervals until two
      negative culture results were obtained. Results One hundred and thirty-two cats
      were included, of which 28 (21.2%) were culture positive and 104 (78.8%) culture
      negative for M canis. PCR correctly identified all culture-positive cats and
      92/104 culture negative cats; there were 12 false-positive PCR results. The
      sensitivity and specificity of PCR were 100% (95% confidence interval [CI] 87.7
      100) and 88.5% (95% CI 80.7-93.9), respectively. Data from 17 cats were available
      for assessment of mycological cure. At the time of the first and second negative
      fungal cultures, 14/17 (82.4%) and 11/17 (64.7%) tested PCR positive,
      respectively. Conclusions and relevance PCR showed high sensitivity and
      specificity for diagnosis of M canis dermatophytosis compared with fungal
      culture, but was unreliable for identifying mycological cure. False-positive
      results were relatively common. There were no false-negative PCR results and a
      negative PCR test was a reliable finding in this study. The ability to rapidly
      diagnose or rule out dermatophytosis could be a valuable tool to increase life
      saving capacity in animal shelters.

PMID- 29172911
TI  - Response to Galvis et al.'s "Myopia rates in a genetically isolated population".

PMID- 29172912
TI  - Patient-Oncologist Communication: Sharing Decisions in Cancer Care.

PMID- 29172913
TI  - Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer:
      American Society of Clinical Oncology Clinical Practice Guideline Update Summary.

PMID- 29172914
TI  - Community Nurses' Experiences Regarding the Meaning and Promotion of Healthy
      Aging in Northeastern Thailand.
AB  - PURPOSE: Describe community nurses' experiences regarding the meaning and
      promotion of healthy aging in northeastern Thailand. METHOD: Data were collected
      through five focus group interviews with 36 community nurses in northeastern
      Thailand. Latent content analysis was conducted to analyze the data. FINDINGS:
      Healthy aging was characterized by the interconnection of older persons, older
      persons' family members, and the community. Healthy aging was associated with two
      themes: "being strong" and "being a supporter and feeling supported." The nurses'
      experiences in promoting healthy aging were described by the themes "providing
      health assessment," "sharing knowledge," and "having limited resources."
      CONCLUSIONS: The findings of this study provide a deeper understanding of the
      meaning of healthy aging from a holistic viewpoint. Community nurses must pay
      attention to older persons and their surroundings when planning how to promote
      healthy aging. Person-centeredness should be applied in practice to promote
      healthy aging. The current findings contribute useful information that should
      help policy makers develop healthy aging strategies in Thailand.

PMID- 29172915
TI  - Sedentary Behavior, Psychosocial Stress Indicators, and Health-Risk Behaviors
      Among Adolescents in Northeastern Brazil.
AB  - OBJECTIVES: To analyze psychosocial stress indicators and health-risk behaviors
      associated with sedentary behavior. METHODS: This is a cross-sectional school
      based study with a representative sample of high school students enrolled in
      public state schools of Sergipe, Brazil, with the sample composed of 3992
      adolescents aged 14-19 years. Data were collected through self-administered
      questionnaire. The time spent in activities, such as watching television, playing
      computer games, chatting with friends, and playing cards or dominoes, was used as
      a measure of sedentary behavior (>2 h/d = exposed). Level of physical activity,
      smoking, stress perception, feelings of loneliness, trouble sleeping, and
      consumption of fruits and vegetables, soft drinks, alcohol, and drugs were
      analyzed. Binary logistic regression analysis was used for association among
      variables. RESULTS: The prevalence of sedentary behavior was 46.7% and was
      associated with low levels of physical activity, consumption of soft drinks,
      negative stress perception, feelings of loneliness, and trouble sleeping.
      CONCLUSION: This study showed high proportion of adolescents with sedentary
      behavior, especially among those who are insufficiently active and exposed to
      psychosocial stress indicators.

PMID- 29172916
TI  - Re: Hand-assisted laparoscopic versus laparoscopic nephrectomy as outpatient
      procedures: a prospective randomized study.

PMID- 29172917
TI  - Prospective evaluation of a protocol for transitioning porcine lente insulin
      treated diabetic cats to human recombinant protamine zinc insulin.
AB  - Objectives The objective was to evaluate a nadir-led protocol for transitioning
      porcine lente insulin suspension (PLIS)-treated diabetic cats onto human
      recombinant protamine zinc insulin (PZIR). Methods Recently diagnosed (<5 months)
      diabetic cats, treated with PLIS q12h for ?6 weeks, were recruited. Fructosamine,
      24 h blood glucose curve (BGC), quality of life assessment (DIAQoL-pet score) and
      Diabetic Clinical Score (DCS) were assessed at enrolment (PLIS-treated) and 2, 4
      and 12 weeks after transitioning to PZIR (starting dose 0.2-0.7 U/kg q12h). Short
      duration of insulin action was defined as <9 h. Linear mixed effects modelling
      assessed for change in fructosamine, mean blood glucose (MBG) during BGCs, DIAQoL
      pet score, DCS and q12h insulin dose. McNemar's tests compared the proportion of
      cats with hypoglycaemia at week 0 (PLIS-treated) and week 4 (PZIR-treated).
      Results Twenty-two cats were recruited. Median PLIS dose at enrolment was 0.5
      U/kg (interquartile range 0.3-0.7 U/kg) q12h, equalling median PZIR starting dose
      (0.5 U/kg; interquartile range 0.3-0.7 U/kg q12h). Transitioning was followed by
      significant decreases in fructosamine ( P = 0.00007), insulin dose ( P = 0.02),
      DCS ( P = 8.1 * 10-8) and DIAQoL-pet score ( P = 0.003), indicating improved
      quality of life. MBG did not alter significantly ( P = 0.1). Five cats (22.7%)
      achieved remission. Hypoglycaemia was recorded in 30/190 12 h BGCs (15.8%) and
      five cats experienced clinical hypoglycaemia. The proportion of cats with
      hypoglycaemia did not differ between PLIS (week 0) and PZIR (week 4) ( P = 1.0).
      Duration of action was analysed in 19 cats. Six cats (31.6%) showed short
      duration of action on PLIS, compared with two cats (10.5%) after 4 weeks on PZIR.
      All six cats with short PLIS duration showed duration of ?9 h on PZIR.
      Conclusions and relevance Used alongside a low-carbohydrate diet, transitioning
      to PZIR was associated with significantly improved clinical signs and quality of
      life, with some cats achieving remission. Transition to PZIR should be considered
      for cats with short duration of action on PLIS.

PMID- 29172918
TI  - Diagnostic performances of manual and automated reticulocyte parameters in
      anaemic cats.
AB  - Objectives The objective of this study was to evaluate the diagnostic
      performances of manual and instrumental measurement of reticulocyte percentage
      (Ret%), reticulocyte number (Ret#) and reticulocyte production index (RPI) to
      differentiate regenerative anaemia (RA) from non-regenerative anaemia (NRA) in
      cats. Methods Data from 106 blood samples from anaemic cats with manual counts (n
      = 74; 68 NRA, six RA) or instrumental counts of reticulocytes (n = 32; 25 NRA,
      seven RA) collected between 1995 and 2013 were retrospectively analysed.
      Sensitivity, specificity and positive likelihood ratio (LR+) were calculated
      using either cut-offs reported in the literature or cut-offs determined from
      receiver operating characteristic (ROC) curves. Results All the reticulocyte
      parameters were significantly higher in cats with RA than in cats with NRA. All
      the ROC curves were significantly different ( P <0.001) from the line of no
      discrimination, without significant differences between the three parameters.
      Using the cut-offs published in literature, the Ret% (cut-off: 0.5%) was
      sensitive (100%) but not specific (<75%), the RPI (cut-off: 1.0) was specific
      (>92%) but not sensitive (<15%), and the Ret# (cut-off: 50 * 103/ul) had a
      sensitivity and specificity >80% and the highest LR+ (manual count: 14;
      instrumental count: 6). For all the parameters, sensitivity and specificity
      approached 100% using the cut-offs determined by the ROC curves. These cut-offs
      were higher than those reported in the literature for Ret% (manual: 1.70%;
      instrumental: 3.06%), lower for RPI (manual: 0.39; instrumental: 0.59) and
      variably different, depending on the method (manual: 41 * 103/ul; instrumental:
      57 * 103/ul), for Ret#. Using these cut-offs, the RPI had the highest LR+
      (manual: 22.7; instrumental: 12.5). Conclusions and relevance This study
      indicated that all the reticulocyte parameters may confirm regeneration when the
      pretest probability is high, while when this probability is moderate, RA should
      be identified using the RPI providing that cut-offs <1.0 are used.

PMID- 29172919
TI  - The drill wobble effect: oversizing the femoral tunnel during ACL reconstruction.
AB  - OBJECTIVES: In ACL reconstruction, autologous tendon graft can be attached to the
      femur, within a boney tunnel, using an Endobutton device. The ultimate aim being
      to achieve biological fixation and incorporation into the bone. Accurate bone
      tunnel diameter to match the tendon graft is vital to biologic incorporation and
      strength. The common technique of in sequence passing a guide wire, a cannulated
      4.5 mm Endobutton drill, then a cannulated femoral socket drill causes the
      guidewire to lose cortical fixation and stability before the femoral socket drill
      is passed. The Objective of this study is to analyze this common technique of
      femoral socket creation and determine if it results in unintentionally oversizing
      the femoral socket due to femoral socket drill-wobble over a destabilised guide
      wire. METHODS: 12 cadaveric femoral pairs equally divided between two groups
      underwent femoral socket creation in one of the two following sequences. Group 1:
      Guidewire, 4.5 mm endobutton drill, 8 mm femoral socket drill. Group 2:
      Guidewire, 8 mm femoral socket drill, 4.5 mm endobutton drill. The created
      femoral tunnels apertures and calibres were measured and then compared for
      accuracy between the two groups. RESULTS: Passing the 4.5 mm drill before the 8
      mm socket drill results in oversized tunnel apertures and calibres when compared
      to passing an 8 mm socket drill after the 4.5 mm drill has been passed
      (p<0.0001). CONCLUSION: To most precisely create an 8 mm femoral socket in ACL
      reconstruction, the 8 mm femoral socket reamer followed by the 4.5 mm should be
      passed over the guide wire to prevent guide wire destabilization and drill
      wobble.

PMID- 29172920
TI  - Clinicopathologic Features of Benign Neurogenic Tumor of Urinary Bladder.
AB  - BACKGROUND: Benign neurogenic tumor involving the urinary bladder is a very rare
      and heterogeneous disease group. The clinical and radiological diagnosis may be
      difficult because of the disease's rarity and the histological similarities of
      each disease especially in needle biopsy specimens. However, accurate diagnosis
      is very important because the clinical course of each disease, even within the
      same diseases, is quite variable. In this study, we investigated 7 benign
      neurogenic tumors to better understand the rare disease entity in the urinary
      bladder by analyzing histological and immunohistochemical findings and comparing
      clinicopathologic features. METHODS: We collected the cases by searching the
      medical records database of Seoul National University Hospital from 2000 to 2016.
      RESULTS: We identified 3 ganglioneuromas, 2 schwannomas, 1 neurofibroma, and 1
      granular cell tumor involving the urinary bladder. There were some limitations
      for the initial clinical and radiological diagnosis and even pathologic diagnosis
      using needle biopsy specimens. One infant patient was diagnosed radiologically
      with rhabdomyosarcoma, but the final diagnosis changed to ganglioneuromatosis.
      The initial needle biopsy diagnosis of 2 ganglioneuroma cases showed
      neurofibroma. All patients underwent a local resection, and 1 granular cell tumor
      patient suffered with pain because of a recurrent tumor. One neurofibromatosis
      patient had a lesion appear 34 months after the bladder operation, so he
      underwent repeated debulking operations, but he was diagnosed with malignant
      transformation after 8 years. CONCLUSIONS: An understanding of benign neurogenic
      tumors involving the urinary bladder and the sharing of rare experiences
      surrounding them are required to provide accurate diagnoses.

PMID- 29172921
TI  - Immunity and inflammation predictors for short-term outcome of stroke in young
      adults.
AB  - BACKGROUND: The current study was conducted to identify independent predictors of
      severity and short-term outcome of first-ever ischemic stroke in young adults.
      METHODS: We retrospectively enrolled 325 consecutive patients aged 18-49 years
      with first-ever ischemic stroke admitted to our center between April 2013 and
      June 2015. Variables were systematically registered and compared between patients
      with different neurological severity (mild stroke: National Institutes of Health
      Stroke Scale [NIHSS] <= 8 and severe stroke: >8) and different stroke outcome
      (favorable: modified Rankin scale score 0-2 and unfavorable: 3-5 or death) at 14
      days after stroke onset. RESULTS: A total of 325 patients fulfilled the inclusion
      criteria. There were 242 patients with mild stroke. They exhibited lower white
      blood cell (WBC), globulin, plasma glucose, fibrinogen (Fib) levels and higher
      albumin, albumin/globulin (A/G), free triiodothyronine (FT3) levels. Logistic
      regression analysis showed that FT3 (?3.18) and WBC (?7.1) were independent
      predictors. There were 122 patients demonstrating an unfavorable outcome. Higher
      WBC, globulin, plasma glucose and Fib levels, lower albumin, FT3, A/G levels,
      higher NIHSS score and longer hospital stay were significantly associated with
      unfavorable outcome. In the logistic regression model, we found that A/G (?1.56),
      FT3 (?4.09) and WBC (?7.1) were independent predictors for short-term outcome.
      CONCLUSIONS: Our data suggested that higher A/G, FT3 levels served as independent
      predictors of favorable outcome, and a higher FT3 value may also predict mild
      stroke, while higher WBC may predict a poor functional outcome and severe stroke
      in patients with acute ischemia.

PMID- 29172922
TI  - Thiol/disulfide homeostasis in pregnant women with obstructive sleep apnea
      syndrome.
AB  - BACKGROUND: Repetitive episodes of hypoxia and reoxygenation during sleep in
      patients with obstructive sleep apnea syndrome (OSAS) resemble an ischemia
      reperfusion injury. We aimed to test the hypothesis that oxidative stress occurs
      in pregnant women with OSAS. We also aimed to compare thiol/disulfide homeostasis
      with ischemia-modified albumin (IMA) and total antioxidant capacity (TAC) as
      markers of ischemia-reperfusion injury in pregnant women with and without OSAS
      and healthy control. METHODS: This study included 29 pregnant women with OSAS, 30
      women without OSAS in the third trimester applying for periodic examinations, and
      30 healthy women. Serum IMA and TAC (using the ferric reducing power of plasma
      method) were measured. Serum thiol/disulfide homeostasis was determined by a
      novel automated method. RESULTS: The mean age of the pregnant women with OSAS was
      31.0 +/- 4.7 years with a mean gestational age of 36.5 +/- 3.0 weeks. The mean
      age of pregnant women without OSAS was 29.8 +/- 4.9 years with a mean gestational
      age of 36.9 +/- 2.7 weeks. The mean age of the nonpregnant control group was 29.7
      +/- 6.4 years. Both native thiol (291 +/- 29 MUmol/L versus 314 +/- 30 MUmol/L; p
      = .018) and total thiol (325 +/- 32 versus 350 +/- 32, p = .025) levels were
      lower in pregnant women with OSAS compared to pregnant women without OSAS,
      respectively (p < .01). CONCLUSIONS: This is the first study demonstrating the
      thiol/disulfide homeostasis in pregnant women with OSAS. Native thiol and total
      thiol levels were lower in pregnant women with OSAS compared to those without
      OSAS. However, dynamic thiol/disulfide homeostasis parameters cannot provide
      valuable information to discriminate OSAS in pregnant women.

PMID- 29172923
TI  - Psychosocial Outcomes 12 Months Following a Dose-Response Aerobic Exercise
      Intervention in Postmenopausal Women.
AB  - BACKGROUND: We previously reported no postintervention differences in quality of
      life and other psychosocial outcomes when comparing 12-month high versus moderate
      volume of aerobic exercise in postmenopausal women. Here, we report the 24-month
      follow-up for these outcomes. METHODS: At 24-month follow-up, 333 out of 400
      postmenopausal women were randomized to a year-long intervention of 150
      (moderate) or 300 (high) minutes per week of aerobic exercise returned a battery
      of self-reported measures assessing quality of life, psychosocial outcomes, and
      sleep quality, also assessed at baseline and postintervention. Intention-to-treat
      analyses using linear models were conducted to determine the changes between
      baseline and 24-month follow-up. RESULTS: No significant effects between moderate
      and high-volume aerobic exercise groups were observed among any outcomes. There
      was some evidence of effect moderation by baseline body mass index in relation to
      quality of life, psychosocial outcomes, and sleep quality, where obese women
      benefitted from the moderate-volume exercise and nonobese women benefitted from
      the high-volume exercise prescription. CONCLUSION: Although high-volume aerobic
      exercise did not improve psychosocial outcomes when compared with moderate volume
      at the 24-month follow-up, we did observe potential effect of moderation between
      obese and nonobese women. Confirmation of these interactions is warranted in this
      population.

PMID- 29172925
TI  - Parents' Experiences and Responses to an Intervention for Psychological
      Preparation of Children and Families During the Child's Radiotherapy.
AB  - The aim of this study was to evaluate parents' experiences and responses to a
      systematic intervention for psychological preparation of children and families
      during the child's radiotherapy (RT) treatment. In this case-control study at 3
      pediatric RT centers, an intervention with a preparatory kit, including age
      adjusted information on tablets, gift of a stuffed toy or a pair of headphones, a
      parent booklet, and toy models of the computed tomography and RT machines was
      implemented. For evaluation, a mixed methods data collection was conducted. A
      total of 113 parents of children undergoing RT were included-n = 59 in the
      baseline group and n = 54 in the intervention group. Health-related quality of
      life was rated low, but parents in the intervention group expressed less anxiety
      after the RT compared with the baseline group. They found information suitable
      for their young children, siblings, and friends were involved and the toy models
      were used for play. Parents expressed positive feelings due to close interaction
      with staff and each other within the family. The solutions developed within a
      human-centered design approach and shaped as a systematic family-centered
      strategy contributed to parents understanding and coping with the child's RT.

PMID- 29172924
TI  - PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal
      ischemia-reperfusion injury.
AB  - Damaged or dysfunctional mitochondria are toxic to the cell by producing reactive
      oxygen species and releasing cell death factors. Therefore, timely removal of
      these organelles is critical to cellular homeostasis and viability. Mitophagy is
      the mechanism of selective degradation of mitochondria via autophagy. The
      significance of mitophagy in kidney diseases, including ischemic acute kidney
      injury (AKI), has yet to be established, and the involved pathway of mitophagy
      remains poorly understood. Here, we show that mitophagy is induced in renal
      proximal tubular cells in both in vitro and in vivo models of ischemic AKI.
      Mitophagy under these conditions is abrogated by Pink1 and Park2 deficiency,
      supporting a critical role of the PINK1-PARK2 pathway in tubular cell mitophagy.
      Moreover, ischemic AKI is aggravated in pink1 andpark2 single- as well as double
      knockout mice. Mechanistically, Pink1 and Park2 deficiency enhances mitochondrial
      damage, reactive oxygen species production, and inflammatory response. Taken
      together, these results indicate that PINK1-PARK2-mediated mitophagy plays an
      important role in mitochondrial quality control, tubular cell survival, and renal
      function during AKI.

PMID- 29172927
TI  - Measuring Eating Compulsivity in the Wider Clinical Context.

PMID- 29172926
TI  - Sumoylation Contributes to Timekeeping and Temperature Compensation of the Plant
      Circadian Clock.
AB  - The transcriptional circadian clock network is tuned into a 24-h oscillator by
      numerous posttranslational modifications on the proteins encoded by clock genes,
      differentially influencing their subcellular localization or activity. Clock
      proteins in any circadian organism are subject to posttranslational regulation,
      and many of the key enzymes, notably kinases and phosphatases, are functionally
      conserved between the clocks of mammals, fungi, and plants. We now establish
      sumoylation, the posttranslational modification of target proteins by the
      covalent attachment of the small ubiquitin-like modifier protein SUMO, as a novel
      mechanism regulating key clock properties in the model plant Arabidopsis. Using 2
      different approaches, we show that mutant plant lines with decreased or increased
      levels of global sumoylation exhibit shortened or lengthened circadian period,
      respectively. One known functional role of sumoylation is to protect the proteome
      from temperature stress. The circadian clock is characterized by temperature
      compensation, meaning that proper timekeeping is ensured over the full range of
      physiologically relevant temperatures. Interestingly, we observed that the period
      defects in sumoylation mutant plants are strongly differential across
      temperature. Increased global sumoylation leads to undercompensation of the clock
      against temperature and decreased sumoylation to overcompensation, implying that
      sumoylation buffers the plant clock system against differential ambient
      temperature.

PMID- 29172928
TI  - Is Little Control Over Eating Always a Compulsive Eating Behavior?

PMID- 29172929
TI  - Telehealth for the management of blood pressure in patients with chronic kidney
      disease: A systematic Review.
AB  - Background Most patients with chronic kidney disease (CKD) fail to achieve blood
      pressure (BP) management as recommended. Meanwhile, the effects of promising
      intervention and telehealth on BP control in CKD patients remain unclear. We
      aimed to evaluate the efficacy of telehealth for BP in CKD non-dialysis patients.
      Methods Databases including MEDLINE, EMBASE, CENTRAL, CNKI, Wanfang, VIP and CBM
      were systematically searched for randomised controlled trials or quasi-randomised
      controlled trials on telehealth for BP control of CKD3-5 non-dialysis patients.
      We analysed systolic blood pressure (SBP), diastolic blood pressure (DBP), mean
      arterial pressure (MAP), serum creatinine, and estimated glomerular filtration
      rate (eGFR) with a fixed-effects model. Results Three studies, with total 680
      subjects, were included in our systematic review and two were included for meta
      analysis. Pooled estimates showed decreased SBP (pooled mean difference (MD), 
      5.10; 95% confidence interval (CI), -11.34, 1.14; p > 0.05, p = 0.11), increased
      DBP (pooled MD, 0.45; 95% CI, -4.24, 5.13; p > 0.05, p = 0.85), decreased serum
      creatinine (pooled MD, -0.38; 95% CI, -0.83, 0.07; p > 0.05, p = 0.10) and
      maintained eGFR (pooled MD, 4.72; 95% CI, -1.85, 11.29; p > 0.05, p = 0.16) in
      the telehealth group. There was no significant difference from the control group.
      MAP (MD, 0.6; 95% CI, -6.61, 7.81; p > 0.05, p = 0.87) and BP control rate ( p >
      0.05, p = 0.8), respectively, shown in two studies also demonstrated no
      statistical significance in the telehealth group. Conclusions There was no
      statistically significant evidence to support the superiority of telehealth for
      BP management in CKD patients. This suggests further studies with improved study
      design and optimised intervention are needed in the future.

PMID- 29172930
TI  - Health Warnings, Smoking Rules, and Smoking Status: A Cross-National Comparison
      of Turkey and the United States.
AB  - OBJECTIVES: This study aimed to compare the prevalence of smoking status (i.e.,
      current, former and never) between the United States and Turkey in terms of age
      and gender, and examine how smoking rules and health warnings are associated with
      smoking status within and between the two countries. METHODS: The study used data
      from the 2012-2013 National Adult Tobacco Survey (U.S. sample, N = 60,196) and
      the 2012 Global Adult Tobacco Survey (Turkey sample, N = 9,581). SAS PROC
      SURVEYLOGISTIC with a weighted variable was used to examine the associations
      between demographics (age, gender and education), smoking rules, health warnings,
      and smoking status within and between the two countries. RESULTS: There was an
      18% current smoking prevalence among U.S. sample, compared to 27% of the Turkey
      sample. The U.S. sample had a higher rate of former smoking compared to the
      Turkey sample (25% vs. 22%). In both countries, being older and male gender
      predicted former smoking while being younger and female gender predicted never
      smoking. Having seen a health warning, and not allowing smoking in the vehicle
      and home positively predicted former and never smoking status. Higher education
      predicted both smoking statuses in the U.S. only. CONCLUSIONS: It is important to
      work with partners particularly in low- and middle-income countries (e.g.,
      Turkey) to combat the global tobacco epidemic. In both counties, cessation
      endeavors should emphasize a comprehensive understanding of smoking status in
      terms of smoking rules in personal spaces and health warnings.

PMID- 29172931
TI  - HIF2A germline-mutation-induced polycythemia in a patient with VHL-associated
      renal-cell carcinoma.
AB  - In this study, we report here a rare case of polycythemia and cRCC in the same
      patient, which may be helpful in understanding clinical features and molecular
      mechanisms underlying VHL-mutation-associated cRCC and polycythemia induced by
      germline mutation of HIF2A. Firstly, we identified a rare but well studied
      germline mutation resulting in polycythemia in HIF2A (c.1609G>A, p.Gly537Arg) in
      the blood of the patient and his daughter. Meanwhile, we identified an
      inactivating VHL mutation (c.391A>T, p.N131Y), as well as TP53 mutation(c.977A>T,
      p.E326V) and mTOR mutation(c.7498A>T, p.I2500F) in renal cancer tissue. Moreover,
      protein levels of VHL, HIF1A, HIF2A, EPO, and VEGF estimated by
      immunohistochemical staining substantiated hyperactivation of the oxygen-sensing
      pathway. In addition, we identified 158 somatic SNP/indel mutations, including 90
      missense/nonsense/splice/stop-loss mutations by whole-exome sequencing (WES) of
      the tumor specimen and matched normal DNA.

PMID- 29172932
TI  - Treatment Seeking among College Students with Comorbid Hazardous Drinking and
      Elevated Mood/Anxiety Symptoms.
AB  - BACKGROUND: Hazardous drinking is prevalent among college students and often
      comorbid with mood and/or anxiety disorders; however, these disorders frequently
      go untreated. Prior studies have found that individuals with comorbid hazardous
      drinking are more likely to seek treatment than those with an hazardous drinking
      alone. OBJECTIVES: The current study tested possible psychological and structural
      explanations to understand these treatment seeking behaviors. METHODS: A sample
      of 222 students identified as hazardous drinkers (AUDIT >= 8) participated from
      September 2010 to April 2011. Behavioral measures designed to mimic actual
      treatment seeking and self-report measures were used to assess treatment seeking
      behaviors, and the influence of psychopathology and individual predictors on
      treatment interest. RESULTS: Students were more interested in treatment for
      emotional problems than for alcohol problems. Further, treatment seeking interest
      was significantly higher among individuals with comorbid hazardous drinking. When
      provided a telephone offer for a free on-campus clinic appointment, no students
      were interested in receiving treatment for alcohol use problems, but some were
      interested in an appointment for emotional problems (n = 13). Of those students
      expressing interest on the phone, seven attended the clinic appointment. Logistic
      regression analyses revealed that students with anxiety, anxiety sensitivity, and
      depression were more likely to attend the clinic appointment.
      Conclusions/Importance: In sum, targeting mood and anxiety disorders may be a
      viable way to increase treatment seeking rates in hazardous drinking college
      students.

PMID- 29172933
TI  - Evaluation of a Web-Based Holistic Stress Reduction Pilot Program Among Nurse
      Midwives.
AB  - PURPOSE: Work-related stress among midwives results in secondary traumatic
      stress, posttraumatic stress disorder, and job attrition. The purpose of this
      pilot project was to evaluate the effectiveness of a holistic, web-based program
      using holistic modalities for stress reduction and improved coping among
      certified nurse-midwives. DESIGN AND METHOD: A convenience sample of 10 midwives
      participated in a web-based holistic stress reduction intervention using yoga,
      mindfulness-based stress reduction, and meditation for four days each week over 4
      weeks. Participants completed pre- and postintervention questionnaires (Perceived
      Stress Scale [PSS] and the Coping Self-Efficacy Scale [CSES]) for evaluation of
      effectiveness. FINDINGS: The PSS means showed improvement in midwives' stress
      (16.4-12.3). The CSES means showed improvement in coping (174.8-214.5).
      Improvement was shown in each subscale of the CSES ("uses problem-focused
      coping": 19.2%; "stops unpleasant thoughts and emotions": 20.3%; and "gets
      support from family and friends": 16.6%). CONCLUSION: Findings suggest the
      potential for stress reduction and improved coping skills after using holistic
      techniques in a web-based format within a cohort of nurse-midwives. Further
      research of web-based, holistic intervention for stress reduction among midwives
      is warranted.

PMID- 29172935
TI  - Association between ultrasonographic appearance of splenic parenchyma and
      cytology in cats.
AB  - Objectives The purpose of this study was to determine whether the presence of a
      splenic mass or a diffusely moth-eaten parenchyma on ultrasonographic scans could
      represent potential criteria of malignancy in the feline spleen. Methods Feline
      patients with ultrasonographic images and cytological analysis of the spleen
      obtained by fine-needle aspiration were retrospectively included in a multicentre
      study. Results One hundred and ninety-five cats met our inclusion criteria. There
      was a lack of agreement between the moth-eaten ultrasonographic appearance of the
      spleen and the presence of a malignant neoplasia on cytological analysis. The
      sensitivity and specificity of a moth-eaten parenchyma for predicting malignant
      neoplastic disease were 13.2% and 84.8%, respectively. The sensitivity and
      specificity of a splenic mass >1 cm for predicting malignant neoplastic disease
      were 21.0% and 94.7%, respectively. A marbled appearance of the splenic
      parenchyma was significantly more frequent among patients examined with a high
      frequency transducer (11-18 MHz) than among those examined with a low-frequency
      transducer (6.6-10 MHz) (27.6% vs 11.1%, respectively; P = 0.004). Similarly,
      although not statistically significant, a moth-eaten parenchyma was more frequent
      in the high-frequency transducer group than in the low-frequency group (17.1% vs
      8.9%, respectively; P = 0.09). Conclusions and relevance Based on our findings, a
      moth-eaten ultrasonographic appearance of the spleen in cats does not necessarily
      reflect a lymphoma or another malignant neoplastic process on cytological
      analysis. The presence of a splenic mass >1 cm on ultrasound is suggestive of
      malignancy in cats. Finally, the transducer frequency must be taken into account
      when assessing the splenic parenchyma, as a high-frequency transducer seems to
      improve the detection of a marbled or moth-eaten parenchyma.

PMID- 29172934
TI  - Early osteoarthritis after slipped capital femoral epiphysis.
AB  - Background and purpose - Slipped capital femoral epiphysis (SCFE) results in a
      more or less pronounced deformity of the proximal femur, sometimes causing
      impingement and early osteoarthritis. We studied early osteoarthritis after SCFE
      and the association with deformity and self-reported hip function, pain, and
      quality of life. Patients and methods - 9 women and 16 men, mean age 32 (21-50)
      years, 19 with unilateral and 6 with bilateral SCFE, participated. All patients
      had primarily been operated by pin or screw with no attempt at reposition of the
      slip. Hips were examined by delayed gadolinium-enhanced magnetic resonance
      imaging of cartilage (dGEMRIC), which quantifies and locates cartilage
      degeneration. Plain radiographs were used to measure deformity as determined by
      the alpha angle. Outcome was assessed by Oxford hip score, Hip Groin Outcome
      score and EQ-5D-Visual scale. Results - In the 19 unilateral SCFE, on the slip
      side dGEMRIC mean value was 533 ms (SD 112, range 357-649) versus mean 589 ms (SD
      125, range 320-788) on the non-slip side, (p = 0.01). The dGEMRIC correlated
      negatively to the alpha angle, correlation coefficient (CC) = -0.60, (p = 0.002).
      Oxford hip score, pain, and EQ-5D-Visual scale correlated to dGEMRIC CC =0.43 (p
      = 0.03), CC =0.40 (p = 0.05), and CC =0.49 (p = 0.01) respectively.
      Interpretation - After SCFE, even relatively mild residual hip deformity can be
      associated with cartilage degeneration. A high alpha angle was associated with
      worse cartilage status. The Oxford hip score identified symptoms even though our
      patients had not previously sought medical care after the index operation.
      Quality of life showed strong inverse correlation with cartilage degeneration.
      Objective assessment of early cartilage degeneration may be useful for treatment
      decisions and follow-up.

PMID- 29172936
TI  - Previously undescribed vitamin D C-3 epimer occurs in substantial amounts in the
      blood of cats.
AB  - Objectives The aim of this report is to describe the identification of a novel
      vitamin D metabolite, a C-3, alpha-epimer of 25-hydroxycholecalciferol (3-epi
      25(OH)D3), in serum and plasma extracts of cat blood and compare its abundance in
      cat, dog and rat serum to 25-hydroxycholecalciferol (25(OH)D3), a conventional
      marker of vitamin D status. Methods Serum 25(OH)D3 and 3-epi-25(OH)D3
      concentrations were measured in healthy cohorts of cats (n = 8), dogs (n = 8) and
      rats (n = 17) using validated reverse and normal-phase high-performance liquid
      chromatography methods. The methods were verified using liquid chromatography
      tandem mass spectrophotometry. Dietary intake and dietary concentrations of
      vitamin D were also measured for evaluation of species differences and effect of
      dietary change on vitamin D metabolite concentrations. Differences between cat
      serum and plasma metabolite concentrations were determined. Results Detectable
      concentrations of 3-epi-25(OH)D3 were observed in all cats and rats. No 3-epi
      25(OH)D3 was detected in dogs, where our limit of detection was 5 ng/ml. There
      were significant differences ( P <0.05) in serum concentrations of 25(OH)D3 and 3
      epi-25(OH)D3 among species, with cats having the greatest concentrations of both
      metabolites. Serum and plasma results were not significantly different. A diet
      change, which resulted in an increase in vitamin D intake among the cats,
      affected serum concentration with an increase ( P = 0.004) in 3-epi-25(OH)D3 but
      no significant change in 25(OH)D3. Conclusions and relevance Serum and plasma of
      cats contain 3-epi-25(OH)D3 in varied and extraordinary concentrations, much
      greater than in rats and certainly than that of dogs, a species for which the
      metabolite was not detected. Importantly, this finding indicates a C-3
      epimerization pathway is quantitatively significant for vitamin D metabolism in
      domestic cats, making 3-epi-25(OH)D3 assays essential for the evaluation of
      vitamin D status in cats and positioning the cat as a novel model for study of
      this pathway.

PMID- 29172938
TI  - Corrigendum.

PMID- 29172937
TI  - Panretinal Photocoagulation: A Review of Complications.
AB  - Panretinal photocoagulation (PRP) is a mainstay of therapy for retinal ischemic
      disease. The procedure involves creating thermal burns in the peripheral retina
      leading to tissue coagulation, the overall consequence of which is improved
      retinal oxygenation. While highly effective, there have been concerns
      historically regarding the anatomic effects and visual complications following
      PRP, the most common of which include choroidal effusions, exudative retinal
      detachments, macular edema, visual field deficits, and night vision defects. The
      occurrence of these complications is closely tied to laser parameters such as
      increased duration and power and intensive treatment in a single sitting, all of
      which cause increased dispersion of thermal energy within the retina and choroid.
      The advent of newer laser delivery systems, such as the multispot pattern laser,
      has greatly mitigated but not eliminated these issues. The following article
      reviews the most common complications following PRP treatment, including reported
      occurrences, inciting factors, and underlying pathophysiology.

PMID- 29172940
TI  - Creating a test blueprint for a progress testing program: A paired-comparisons
      approach.
AB  - CONTEXT: Creating a new testing program requires the development of a test
      blueprint that will determine how the items on each test form are distributed
      across possible content areas and practice domains. To achieve validity,
      categories of a blueprint are typically based on the judgments of content
      experts. How experts judgments are elicited and combined is important to the
      quality of resulting test blueprints. METHODS: Content experts in dentistry
      participated in a day-long faculty-wide workshop to discuss, refine, and confirm
      the categories and their relative weights. After reaching agreement on categories
      and their definitions, experts judged the relative importance between category
      pairs, registering their judgments anonymously using iClicker, an audience
      response system. Judgments were combined in two ways: a simple calculation that
      could be performed during the workshop and a multidimensional scaling of the
      judgments performed later. RESULTS: Content experts were able to produce a set of
      relative weights using this approach. The multidimensional scaling yielded a
      three-dimensional model with the potential to provide deeper insights into the
      basis of the experts' judgments. CONCLUSION: The approach developed and
      demonstrated in this study can be applied across academic disciplines to elicit
      and combine content experts judgments for the development of test blueprints.

PMID- 29172939
TI  - Rice ERECT LEAF 1 acts in an alternative brassinosteroid signaling pathway
      independent of the receptor kinase OsBRI1.
AB  - ERECT LEAF 1 (ELF1) was previously identified as a component of brassinosteroid
      signaling in rice. A double mutant obtained by crossing elf1-1 (a null mutant of
      ELF1) with d61-1 (a leaky mutant of OsBRI1) showed a more severe phenotype than
      did the elf1-1 single mutant, resembling that of a severe brassinosteroid
      deficient mutant. Microarray analysis showed that the gene expression profile of
      elf1-1 was distinct from that of d61-12 (a leaky mutant of OsBRI1 with a
      phenotype similar to that of elf1-1), and fewer than half of genes differentially
      expressed between the wild-type and elf1-1 showed similar differences in d61-12
      relative to the wild-type. These results indicate that less than half of ELF1
      regulated genes in rice seedlings are affected by OsBRI1, and suggest that ELF1
      acts in a rice brassinosteroid signaling pathway different from that initiated by
      OsBRI1. Gene expression analysis showed that some stress response-related genes
      were induced in elf1-1 but not in d61-12, and 8 of 9 genes oppositely regulated
      in elf1-1 and d61-12 were significantly up- or down-regulated in both elf1-1 and
      jasmonic acid-treated wild-type. These results imply that ELF1 suppresses stress
      induced signalling, and that jasmonic acid signaling is stimulated in elf1-1;
      therefore, ELF1 may be involved in the brassinosteroid-mediated suppression of
      jasmonic acid response in rice.

PMID- 29172941
TI  - Reporting of adverse events following immunizations in Ghana - Using
      disproportionality analysis reporting ratios.
AB  - BACKGROUND: Timely reporting of safety information post vaccination is pivotal
      for the success of any vaccination program. Reports of adverse events following
      immunization (AEFI) of 6 different vaccinations from Ghana were analysed for
      signals. METHODS: De-identified data from active surveillance for AEFIs after
      2009 AH1N1 influenza, yellow fever, meningitis, measles-rubella, pneumococcal
      rotavirus and human papilloma virus vaccinations were used. All vaccinations
      occurred between January 2010 and December 2013. The ten most occurring events
      for each vaccination were captured and arranged using Medical Dictionary for
      Regulatory Authorities (MedDRA) Preferred Term (PT) and System Organ
      Classification (SOC) codes. Adverse event incidence rates were calculated for
      each vaccine type, and signals were generated using proportional reporting ratios
      (PRR). RESULTS: A total number of 5,141 reports were analysed ranging from 33
      (human papilloma virus) to 1958 (measles-rubella). Between 22% and 55% of all
      AEFIs per vaccine type were collected on the day of vaccination. For each vaccine
      type, at least 87% of all reported AEFIs occurred in the first 7 days post
      vaccination. Multiple reports were received per vaccine type. For the MR vaccine,
      urticarial recorded the highest attack rate of 6.6 (95% CI 6.2, 7.1) per 100,000
      vaccines. The AEFI with the highest PRR for both human papilloma and measles
      rubella vaccines was abdominal pain, recording a PRR of 8.15 (95% CI 3.46, 19.23)
      and 43.75 (95% CI 17.81, 107.45) respectively. CONCLUSION: These results
      underscore the competency of public health systems in sub-Saharan African
      countries (like Ghana) to identify most frequently occurring and important
      vaccine related safety issues.

PMID- 29172942
TI  - Protein quality control is essential for the circadian clock in plants.
AB  - Extreme environmental conditions, such as heat and cold, often disturb cellular
      proteostasis, resulting in protein denaturation and oxidative damage that
      threaten cell viability. Therefore, living organisms have evolved versatile
      protein quality control mechanisms that clear damaged proteins from cellular
      compartments. It has been shown that a repertoire of molecular chaperones,
      including heat shock proteins (HSPs), works together with ubiquitin-proteasome
      systems in this biochemical process in animals and yeast. However, the protein
      quality control systems have not been well-characterized in plants. We have
      recently reported that the E3 ubiquitin ligase ZEITLUPE (ZTL), a central
      component of the plant circadian clock, constitutes a protein quality control
      system in conjunction with HSP90, which is responsible for clearing denatured
      protein aggregates at high temperatures. The ZTL-HSP90 protein complexes are
      colocalized in insoluble fractions in heat-exposed plants. Notably, lack of ZTL
      reduces protein polyubiquitination and disrupts the robustness of circadian
      rhythms under heat stress conditions, providing a novel role of ZTL: it mediates
      a heat-responsive protein quality control to sustain the clock function. We
      summarize the potential roles of ZTL in thermal responses and stability of the
      circadian clock in plants.

PMID- 29172943
TI  - Tissue Edema, Fluid Balance, and Patient Outcomes in Severe Sepsis: An Organ
      Systems Review.
AB  - Severe sepsis and septic shock remain among the deadliest diseases managed in the
      intensive care unit. Fluid resuscitation has been a mainstay of early treatment,
      but the deleterious effects of excessive fluid administration leading to tissue
      edema are becoming clearer. A positive fluid balance at 72 hours is associated
      with significantly increased mortality, yet ongoing fluid administration beyond a
      durable increase in cardiac output is common. We review the pathophysiologic and
      clinical data showing the negative effects of edema on pulmonary, renal, central
      nervous, hepatic, and cardiovascular systems. We discuss data showing increased
      morbidity and mortality following nonjudicious fluid administration and challenge
      the assumption that patients who are fluid responsive are also likely to benefit
      from that fluid. The distinctions between fluid requirement, responsiveness, and
      tolerance are central to newer concepts of resuscitation. We summarize data in
      each organ system showing a predictable increase in morbidity and mortality with
      nonbeneficial fluid administration, providing a better framework for precision in
      volume management of the patient with severe sepsis.

PMID- 29172944
TI  - "Making the Ordinary More Extraordinary": Exploring Creativity as a Health
      Promotion Practice Among Older Adults in a Community-Based Professionally Taught
      Arts Program.
AB  - PURPOSE: Document psychosocial and mental well-being outcomes across artistic
      mediums and classes of a community-based, professionally taught arts program for
      older adults. METHOD: One hundred and thirty-eight students completed pre and
      post class surveys about expectations/experiences when creating art in four
      mediums (painting, drawing, mixed media, creative writing). In addition, 162
      students composed one-paragraph biographical narratives describing their
      relationships to art and creative engagement. Text was coded for a priori and
      emergent themes to identify and explain well-being outcomes. FINDINGS: Results of
      this new study supported and expanded our earlier model of improved psychosocial
      and mental well-being due to creative engagement: impact of class-cognitive focus
      and outcome of class-cognitive focus, happiness as component of mental and social
      well-being due to creative engagement, and robust sense of calmness during the
      creative process. CONCLUSION: Results suggest that professionally taught arts
      programming can contribute to well-being and may contribute to brain health
      through promoting an enhanced ability to focus. Holistic nursing treats
      creativity as healing, and results suggest that creative engagement should be a
      priority in therapeutic programming, and individual counseling for older adults
      to begin engaging in some form of art making suited to their abilities should be
      incorporated into nursing practice.

PMID- 29172945
TI  - A phase I, randomized, controlled, dose-ranging study of investigational
      acellular pertussis (aP) and reduced tetanus-diphtheria-acellular pertussis
      (TdaP) booster vaccines in adults.
AB  - Despite high vaccination coverage worldwide, pertussis has re-emerged in many
      countries. This randomized, controlled, observer-blind phase I study and
      extension study in Belgium (March 2012-June 2015) assessed safety and
      immunogenicity of investigational acellular pertussis vaccines containing
      genetically detoxified pertussis toxin (PT) (NCT01529645; NCT02382913). 420
      healthy adults (average age: 26.8 +/- 5.5 years, 60% female) were randomized to 1
      of 10 vaccine groups: 3 investigational aP vaccines (containing pertussis
      antigens PT, filamentous hemagglutinin [FHA] and pertactin [PRN] at different
      dosages), 6 investigational TdaP (additionally containing tetanus toxoid [TT] and
      diphtheria toxoid [DT]), and 1 TdaP comparator containing chemically inactivated
      PT. Antibody responses were evaluated on days 1, 8, 30, 180, 365, and
      approximately 3 years post-booster vaccination. Cell-mediated immune responses
      and PT neutralization were evaluated in a subset of participants in pre-selected
      groups. Local and systemic adverse events (AEs), and unsolicited AEs were
      collected through day 7 and 30, respectively; serious AEs and AEs leading to
      study withdrawal were collected through day 365 post-vaccination. Antibody
      responses against pertussis antigens peaked at day 30 post-vaccination and then
      declined but remained above baseline level at approximately 3 years post
      vaccination. Responses to FHA and PRN were correlated to antigen dose. Antibody
      responses specific to PT, toxin neutralization activity and persistence induced
      by investigational formulations were similar or significantly higher than the
      licensed vaccine, despite lower PT doses. Of 15 serious AEs, none were considered
      vaccination-related; 1 led to study withdrawal (premature labor, day 364; aP4
      group). This study confirmed the potential benefits of genetically detoxified PT
      antigen. All investigational study formulations were well tolerated.

PMID- 29172946
TI  - Postprandial gut microbiota-driven choline metabolism links dietary cues to
      adipose tissue dysfunction.
AB  - The human body is an integrated circuit between microbial symbionts and our Homo
      sapien genome, which communicate bi-directionally to maintain homeostasis within
      the human meta-organism. There is now strong evidence that microbes resident in
      the human intestine can directly contribute to the pathogenesis of obesity and
      associated cardiometabolic disorders. In fact, gut microbes represent a filter of
      our greatest environmental exposure - the foods we consume. It is now clear that
      we each experience a given meal differently, based on our unique gut microbial
      communities. Biologically active gut microbe-derived metabolites, such as short
      chain fatty acids, secondary bile acids, and trimethylamine-N-oxide (TMAO), are
      now uniquely recognized as contributors to obesity and related cardiometabolic
      disorders. However, mechanistic insights into how microbe-derived metabolites
      promote obesity are largely unknown. Recent work has demonstrated that the meta
      organismal production of the bacterial co-metabolite TMAO is linked to
      suppression of beiging of white adipose tissue in mice and humans. Furthermore,
      the TMAO pathway is becoming an increasingly attractive therapeutic target in
      obesity-associated diseases such as type 2 diabetes, kidney failure, and
      cardiovascular disease. In this commentary we discuss recent findings linking the
      TMAO pathway to obesity-associated disorders, and provide additional insights
      into potential mechanisms driving this microbe-host interaction.

PMID- 29172947
TI  - Crosstalk between WIP and Rho family GTPases.
AB  - Through actin-binding proteins such as the neural Wiskott-Aldrich syndrome
      protein (N-WASP) and WASP-interacting protein (WIP), the Rho family GTPases RhoA,
      Rac1 and Cdc42 are major modulators of the cytoskeleton. (N-)WASP and WIP control
      Rho GTPase activity in various cell types, either by direct WIP/(N-)WASP/Cdc42 or
      potential WIP/RhoA binding, or through secondary links that regulate GTPase
      distribution and/or transcription levels. WIP helps to regulate filopodium
      generation and participates in the Rac1-mediated ruffle formation that determines
      cell motility. In neurons, lack of WIP increases dendritic spine size and
      filamentous actin content in a RhoA-dependent manner. In contrast, WIP deficiency
      in an adenocarcinoma cell line significantly reduces RhoA levels. These data
      support a role for WIP in the GTPase-mediated regulation of numerous actin
      related cell functions; we discuss the possibility that this WIP effect is linked
      to cell proliferative status.

PMID- 29172948
TI  - The effect of frailty on HAI response to influenza vaccine among community
      dwelling adults >= 50 years of age.
AB  - The immune response to vaccine antigens is less robust in older adults because of
      changes in the aging immune system. Frailty, the multi-dimensional syndrome
      marked by losses in function and physiological reserve, is increasingly prevalent
      with advancing age. Frailty accelerates this immunosenescence but the consequence
      of frailty on immune response specific to influenza vaccine among older adults,
      is mixed. An observational, prospective study of 114 adults was conducted in the
      fall of 2013 to assess the association of physical frailty with immune response
      to standard dose influenza vaccine in community-dwelling adults >= 50 years of
      age. Participants were stratified by age (<65 years and >=65 years), and vaccine
      strain (Influenza A/H1N1, A/H3N2 and B) was analyzed separately adjusting for
      body mass index (BMI) and baseline log2 hemagglutination inhibition (HAI) titers.
      Overall, immune responses were lower among those >=65 years of age than those <65
      years. Among those >=65 years there were no significant differences between frail
      and non-frail individuals in seroprotection or seroconversion for any influenza
      strain. Frail individuals <65 years of age compared with non-frail individuals
      were more likely to be seroprotected and to seroconvert post vaccination. Linear
      regression models show the same pattern of significant differences between frail
      and non-frail for those <65 years but no significant differences between frailty
      groups for those >=65 years. Additional research may elucidate the reasons for
      the differences observed between younger frail and non-frail adults.

PMID- 29172949
TI  - Laparoscopic Versus Open Hepatic Resection for Solitary Hepatocellular Carcinoma
      Less Than 5 cm in Cirrhotic Patients: A Randomized Controlled Study.
AB  - BACKGROUND: Current literature is lacking level 1 evidence for surgical and
      oncologic outcomes of hepatocellular carcinoma (HCC) undergoing laparoscopic
      versus open hepatectomy. Aim was to compare feasibility, safety, and surgical and
      oncologic efficiency of laparoscopic versus open liver resection (OLR) in
      management of solitary small (<5 cm) peripheral HCC in Child A cirrhotic
      patients. METHODS: Patients were randomly assigned to either OLR group (25
      patients) or laparoscopic liver resection (LRR) group (LRR: 25 patients). All
      were treated with curative intent aiming at achieving R0 resection using
      radiofrequency-assisted technique. RESULTS: LLR had significantly less operative
      time (120.32 +/- 21.58 versus 146.80 +/- 16.59 minutes, P < .001) and shorter
      duration of hospital stay (2.40 +/- 0.58 versus 4.28 +/- 0.79 days, P < .001),
      with comparable overall complications (25 versus 28%, P = .02). LLR had
      comparative resection time (66.56 +/- 23.80 versus 59.56 +/- 14.74 minutes, P =
      .218), amount of blood loss (250 versus 230 mL, P = .915), transfusion rate (P =
      1.00), and R0 resection rate when compared with OLR. After median follow-up of
      34.43 (31.67-38.60) months, LLR achieved similar adequate oncological outcome of
      OLR, no local recurrence, with no significant difference in early recurrence or
      number of de novo lesions (P = .49). One-year and 3-year disease free survival
      (DFS) rates, 88% and 59%, in the LLR were comparable to corresponding rates of
      84% and 54% in OLR (P = .9). CONCLUSION: LLR is superior to the OLR with
      significantly shorter duration of hospital stay and does not compromise the
      oncological outcomes.

PMID- 29172951
TI  - Usability testing of an electronic pain monitoring system for palliative cancer
      patients: A think-aloud study.
AB  - Pain experienced by advanced cancer patients is often poorly controlled due to
      inadequate assessment. We aimed to test an electronic pain monitoring system
      (PainCheck) with advanced cancer patients and health professionals. In all, 29
      participants (13 patients and 16 health professionals (n = 16)) used PainCheck
      while thinking their thoughts aloud. After the think aloud, both groups were
      asked about their experiences. Think-aloud and semi-structured interview data
      were analysed using framework analysis. Both groups were generally positive about
      PainCheck and found it easy to understand but they had concerns about clinical
      integration. Their concerns related to impact on workload, how lack of response
      may affect patient care and ability to engage with and use the technology.
      PainCheck has the capacity to be useful in clinical practice. For integration to
      be successful, patients and health professionals need guidance on how to use
      PainCheck and the expectations of users need to be clarified.

PMID- 29172950
TI  - The Safety and Feasibility of Three-Dimensional Visualization Technology Assisted
      Right Posterior Lobe Allied with Part of V and VIII Sectionectomy for Right
      Hepatic Malignancy Therapy.
AB  - BACKGROUND: Hepatectomy is the optimal method for liver cancer; the virtual liver
      resection based on three-dimensional visualization technology (3-DVT) could
      provide better preoperative strategy for surgeon. We aim to introduce right
      posterior lobe allied with part of V and VIII sectionectomy assisted by 3-DVT as
      a promising treatment for massive or multiple right hepatic malignancies to
      retain maximum residual liver volume on the basis of R0 resection. METHODS: Among
      126 consecutive patients who underwent hepatectomy, 9 (7%) underwent right
      posterior lobe allied with part of V and VIII sectionectomy. 21 (17%) underwent
      right hemihepatectomy (RH). The virtual RH was performed with 3-DVT, which
      provided better observation of spatial position relationship between tumor and
      vessels, and the more accurate estimation of the remnant liver volume. If remnant
      liver volume was <40%, right posterior lobe allied with part of V and VIII
      sectionectomy should be undergone. Then, the precut line ought to be planned on
      the basis of protecting the portal branch of subsegment 5 and 8. The
      postoperative outcome of patients was compared before and after propensity score
      matching. RESULTS: Nine patients meeting the eligibility criteria received right
      posterior lobe allied with part of V and VIII sectionectomy. The variables,
      including the overall mean operation time, blood transfusion, operation length,
      liver function, and postoperative complications, were similar between two groups
      before and after propensity matching. The postoperative first, third, fifth, and
      seventh days mean value of aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), albumin (ALB), and total bilirubin had no significant
      difference compared with preoperative value. One patient in each group had
      recurrence six months after surgery. CONCLUSION: Right posterior lobe allied with
      part of V and VIII sectionectomy based on 3-DVT is safe and feasible surgery way,
      and can be a very promising method in massive or multiple right hepatic
      malignancy therapy.

PMID- 29172952
TI  - Positive Outcome Expectations and Tobacco Product Use Behaviors in Youth.
AB  - BACKGROUND: Outcome expectations are an important determinant of health behavior,
      according to Social Cognitive Theory; yet recent literature has not examined the
      relationship between outcome expectations and tobacco product use (e.g., use of
      cigarettes, cigars, hookah, e-cigarettes, or smokeless tobacco). OBJECTIVES: This
      study examines if outcome expectations at baseline, among an adolescent cohort of
      never users of tobacco products, predicts tobacco product use (i.e., cigarettes,
      hookah, e-cigarette, cigar, or smokeless tobacco) or susceptibility to use at 6
      month follow-up. METHODS: Data are from the first two waves of a Texas cohort
      study of urban middle school and high school students, which were collected in
      2014-2015. Logistic regression analyses were used; these adjusted for socio
      demographic variables. Analyses were limited to never users of any tobacco
      product at baseline (n = 1999, N = 357,035). RESULTS: Outcome expectations
      related to stress relief predicted ever use of (AOR: 4.21, 95% CI 1.84-9.60) and
      susceptibility (AOR: 2.97, 95% CI 1.01-8.70) to tobacco products. Additional
      outcome expectations (e.g., relaxation, concentration, slimness, etc.) were not
      associated with ever use or susceptibility. Conclusions/Importance: This study
      extends the literature regarding outcome expectations among adolescents regarding
      tobacco products. It is important that interventions offer alternative solutions
      to stress relief that do not include tobacco products.

PMID- 29172953
TI  - Cortactin function in invadopodia.
AB  - Actin remodeling plays an essential role in diverse cellular processes such as
      cell motility, vesicle trafficking or cytokinesis. The scaffold protein and actin
      nucleation promoting factor Cortactin is present in virtually all actin-based
      structures, participating in the formation of branched actin networks. It has
      been involved in the control of endocytosis, and vesicle trafficking, axon
      guidance and organization, as well as adhesion, migration and invasion. To
      migrate and invade through three-dimensional environments, cells have developed
      specialized actin-based structures called invadosomes, a generic term to
      designate invadopodia and podosomes. Cortactin has emerged as a critical
      regulator of invadosome formation, function and disassembly. Underscoring this
      role, Cortactin is frequently overexpressed in several types of invasive cancers.
      Herein we will review the roles played by Cortactin in these specific invasive
      structures.

PMID- 29172954
TI  - AMPK and autophagy control embryonic elongation as part of a RhoA-like
      morphogenic program in nematode.
AB  - Autophagy is the process where cytosolic components are digested by the cell.
      This process is required for cell survival in stressful conditions. It was also
      shown to control cell division and more recently, cell morphology and migration.
      We characterized signalling pathways enabling embryonic epidermal cells of the
      nematode Caenorhabditis elegans to elongate along their antero-posterior axis.
      Previous studies revealed that epidermal cells can adopt either a RhoA-like or a
      Rac1-like morphogenic program. We show here that the AMP-activated protein kinase
      (AMPK) and genes controlling autophagy are required for proper elongation of
      epidermal cells following the RhoA-like program and are dispensable for other
      cells. This suggests that AMPK-autophagy is used by the embryo to fuel the most
      energy-demanding morphogenic processes promoting early elongation.

PMID- 29172955
TI  - Three Poems: Dementia, Ed's Vision, Temporal.

PMID- 29172957
TI  - Exploring Holistic Comfort in Children Who Experience a Clinical Venipuncture
      Procedure.
AB  - PURPOSE: Children often experience the uncomfortable effects of invasive
      procedures as a part of primary care and during times of illness. Holistic
      comfort has been well documented in adult literature but little research exists
      on the understanding of holistic procedural comfort from the child's perspective.
      In this study, holistic comfort related to an invasive venipuncture procedure was
      explored in children age 5 to 7 years and their caregivers of all ages. DESIGN: A
      qualitative descriptive design described by Sandelowski was used. METHOD: The
      philosophical underpinnings of naturalistic inquiry of Guba and Lincoln were
      used. Semistructured interviews were conducted with 13 child and 15 caregiver
      participants. Children also drew pictures to help describe their perceptions.
      FINDINGS: Traditional thematic content analysis described by Hsieh and Shannon
      yielded four overarching themes of holistic comfort related to venipuncture
      procedures in children: Body Comfort, Cognitive and Emotional Comfort, Comfort in
      the Procedure Surroundings, and Comfort Play. CONCLUSIONS: Numerous
      recommendations for future research are included. Implications for nursing and
      related health sciences, organizational and administrative policy, invasive
      procedures, theory, and methods were found and are discussed. Findings from this
      study will assist nurses in providing procedure management for children from a
      holistic care perspective.

PMID- 29172956
TI  - Estrogen and insulin synergistically promote type 1 endometrial cancer
      progression.
AB  - Despite evidence that estrogens and insulin are related to type 1 endometrial
      carcinoma (EC), their synergistic role has not been analyzed. Here, we
      investigated how estrogens cooperate with insulin to promote type 1 EC
      progression. We examined the clinical significance of serum estrogen and insulin
      levels using type 1 EC patients and control subjects. Univariate and multivariate
      logistic regression analyses for total, premenopausal, and postmenopausal
      subjects were performed. Type 1 EC risk was evaluated with respect to estrone,
      estradiol, and insulin levels based on odds ratios (ORs) using stratified data.
      Cell growth in vitro and in vivo, effects of insulin and estradiol on apoptosis
      and cell cycle distribution were measured after estradiol and insulin
      stimulation. Estrone and insulin concentrations were significantly high in type 1
      EC patients and retained positive associations with type 1 EC after adjustment
      for BMI, WHR, diabetes, and hypertension. The odds ratio was significantly high
      for type 1 EC patients with higher levels of estrone/estradiol and insulin than
      for patients with higher levels of either estrone/estradiol or insulin,
      suggesting that estrogen and insulin play a synergistic role in type 1 EC
      carcinogenesis and progression. Compared to EC cells and cell-based xenografts
      treated with estradiol or insulin alone, those treated with estradiol and insulin
      exhibited stronger stimulation. Estrogen and insulin play synergistic roles in
      type 1 EC carcinogenesis and progression, extending our understanding of EC
      risks.

PMID- 29172958
TI  - A systematic review and meta-analysis of lifestyle and body mass index predictors
      of successful assisted reproductive technologies.
AB  - OBJECTIVE: Lifestyle (smoking, drinking alcohol) and body mass index (BMI)
      predictors of successful outcomes in assisted reproductive technology (ART)
      treatments were examined in this meta-analysis. METHOD: A bibliographic search
      was undertaken using six databases. The review was informed by PRISMA/MOOSE
      guidelines. Meta-analytic data were analysed using random effects models.
      RESULTS: We included 77 studies examining effects of BMI, smoking and drinking
      alcohol. Patients with a BMI< =24.9 were significantly more likely to achieve
      LB/pregnancy than with BMI> =25 OR = 1.219 (95% CI:1.128-1.319, z = 4.971, p <
      .001; I2 = 53.779%, p = .001). Non-smokers were significantly more likely to
      achieve a LB or pregnancy than smokers OR = 1.457 (95% CI:1.228-1.727, z = 4.324,
      p < .001; I2 = 51.883; p = .001). Meta-regression revealed the number of embryos
      transferred significantly moderated the effects of smoking on ART outcomes, and
      there was a trend indicating primary infertility and high BMI were also
      significant moderators. The evidence for drinking alcohol was inconclusive due to
      the small number of studies. CONCLUSIONS: This meta-analysis confirms that ART
      treatment success can be predicted with lifestyle factors. Further, non-smokers'
      relative odds of pregnancy/live birth increase as more embryos were transferred
      but there was a trend that the odds of pregnancy/live birth decrease with primary
      infertility and high BMI.

PMID- 29172959
TI  - Adolescents' Perceptions of a Gardening Activity at a Juvenile Justice Center.
AB  - PURPOSE: The purpose of this study was to elicit participants' ( N = 16)
      perceptions of a gardening activity at a juvenile justice center and to determine
      whether past exposure to gardening and farmers markets was associated with their
      perceptions of the gardening experience. DESIGN: This cross-sectional,
      exploratory program evaluation was conducted in partnership with the Kentucky
      Department of Juvenile Justice. Adolescents completing the Cadet Leadership and
      Education Program participated in gardening in order to provide produce to a
      local farmers' market. METHOD: After the growing season, participants were asked
      to complete a nine-item questionnaire about the gardening activity during one of
      their usual classes at the facility. The questionnaire assessed perception of the
      experience and past exposure to gardening and farmers' markets. FINDINGS:
      Participants reported favorably about their participation in the activity,
      knowledge gained from the activity, and their intent to garden in the future.
      Those who had previously gardened had more favorable perception of gardening than
      those who had never gardened. Gardening is an inexpensive means of teaching
      teamwork and delayed gratification and providing a sense of empowerment and may
      benefit at-risk adolescents during incarceration.

PMID- 29172960
TI  - Pantarsal arthrodesis in cats using orthogonal plating.
AB  - Case series summary Pantarsal arthrodesis (PTA) was performed in seven tarsi of
      six cats, using orthogonal (dorsal and medial) veterinary cuttable plates (VCPs)
      without postoperative external coaptation. Short-term outcomes, arthrodesis
      progression and complications were assessed using a retrospective review of case
      notes (veterinary examination) and radiographs. Long-term outcomes were assessed
      via owner questionnaire (Feline Musculoskeletal Pain Index [FMPI]). Mean angle of
      PTA was 136 degrees  (range 116-166 degrees ). Intraoperative complications were
      recorded in two cases, both involving failure of the drill bit during drilling
      for calcaneotibial screws. Postoperative complications were encountered in a case
      of bilateral single-session PTA. These included gastrocnemius myotendinopathy on
      the right, and long-term protrusion of a screw head from the skin on the left.
      Both complications were resolved surgically, through resection of the implicated
      gastrocnemius tendon of insertion and removal of the plate, respectively. FMPI
      assessment was performed for all six cats a mean of 8.8 months (range 6-16
      months) following surgery. Mean score for the first part (assessing ability to
      perform normal activities) was 92.2% (range 80.9-97.1%). Mean score for the
      second part (owner perception of pain) was 95.8% (range 87.5-100%). Mean overall
      score (mean score for parts 1 and 2 combined) was 92.3% (range 81.6-97.4%). PTA
      may be performed in cats using orthogonal VCPs to treat severe tarsal injuries.
      It may be prudent to avoid single-session bilateral PTA in cats. Relevance and
      novel information This case series documents a novel technique as an alternative
      for PTA in cats with talocrural injuries. Long-term outcome and complications
      presented in this case series are evaluated and discussed.

PMID- 29172961
TI  - Penalty-based approaches to evaluating multiplicity adjustments in clinical
      trials: Traditional multiplicity problems.
AB  - Given the importance of addressing multiplicity issues in confirmatory clinical
      trials, several recent publications focused on the general goal of identifying
      most appropriate methods for multiplicity adjustment in each individual setting.
      This goal can be accomplished using the Clinical Scenario Evaluation approach.
      This approach encourages trial sponsors to perform comprehensive assessments of
      applicable analysis strategies such as multiplicity adjustments under all
      plausible sets of statistical assumptions using relevant evaluation criteria.
      This two-part paper applies a novel class of criteria, known as criteria based on
      multiplicity penalties, to the problem of evaluating the performance of several
      candidate multiplicity adjustments. The ultimate goal of this evaluation is to
      identify efficient and robust adjustments for each individual trial and optimally
      select parameters of these adjustments. Part I deals with traditional problems
      with a single source of multiplicity. Two case studies based on recently
      conducted Phase III trials are used to illustrate penalty-based approaches to
      evaluating candidate multiple testing methods and constructing optimization
      algorithms.

PMID- 29172962
TI  - Treatment of mature landfill leachate using hybrid processes of hydrogen peroxide
      and adsorption in an activated carbon fixed bed column.
AB  - In this study, the treatment of mature landfill leachate is evaluated by
      oxidation with hydrogen peroxide (H2O2) combined with adsorption in a granular
      activated carbon (GAC) fixed bed column to determinate the increase in the
      biodegradability index, the reduction of chemical oxygen demand (COD) as well as
      the increase in the useful life of the GAC bed. The sample leachate from Loma de
      Los Cocos Landfill (Cartagena de Indias, Colombia) has a very low
      biodegradability ratio ranging from 0.034 to 0.048 that makes it difficult to
      meet the required water quality level according to the regulations. The COD
      removal is initially monitored in the H2O2 oxidation treatment process. The
      operating conditions such as pH, H2O2 dosage, and the reaction time are optimized
      in this process based on the percentage of COD removal. A maximum COD removal of
      29.9% is achieved at an initial H2O2 concentration of 5000 mg L-1 with a pH of 8
      and the reaction time of 60 min. The hybrid treatment by H2O2-GAC achieved 97.3%
      COD removal and 116% increase in the biodegradability ratio (from 0.072 to 0.134)
      while this ratio was increased by 6.5% with H2O2 alone. Moreover, the useful life
      of the GAC bed is increased from 45 min in the column fed with raw leachate to
      170 min in the column fed with pretreated leachate and 5000 mg L-1 of H2O2 at pH
      of 8 that subsequently increased the activated carbon adsorption capacity. An
      adsorption model for leachate treated with H2O2 is also developed.

PMID- 29172963
TI  - Effect of administration rate on propofol requirement in cats.
AB  - Objectives The objective of this study was to determine the effect of
      administration rate on propofol dose for induction of anesthesia and the effect
      of methadone on this dose. Methods This was a prospective, randomized, blinded
      clinical study. Forty male cats (mean +/- SD age 1.5 +/- 0.8 years) were admitted
      for orchiectomy. Cats were randomly allocated to receive acepromazine (0.05
      mg/kg) with either methadone (MET; 0.3 mg/kg) or saline (SAL; 0.03 ml/kg). Each
      premedication group then received anesthetic induction with propofol at 5 (F) or
      1.5 mg/kg/min (S), resulting in the following four groups: MET-F, SAL-F, MET-S
      and SAL-S. Sedation scores were assigned at 15 and 30 mins after premedication
      using a simple descriptive scale (SDS) and a visual analog scale (VAS). After
      assignment of sedation scores, respiratory frequency ( fR) was recorded, and
      anesthetic induction began and was continued until cats lost their palpebral
      reflexes and jaw tone, and the eye globe rotated ventromedially. The time for
      induction and the total amount of propofol needed was recorded, and intubation
      was then performed. After intubation, fR was also recorded. Results SDS and VAS
      sedation scores were low at 15 and 30 mins after premedication. There was no
      significant difference in sedation scores by time or between the groups at any
      time on any scale. The amount of propofol needed to achieve anesthetic induction
      was 5.3 +/- 1.1 mg/kg in group MET-F, which was statistically lower when compared
      with the other three groups, which demonstrated no difference among them.
      Conclusions and relevance Premedication with acepromazine and methadone was not
      able to produce adequate sedation in healthy cats. The slow induction rate is not
      adequate for use in cats considering that all of the animals demonstrated
      excitement during anesthetic induction. The fast administration rate was able to
      produce adequate induction of anesthesia and reduce the amount of propofol needed
      to achieve intubation only when using methadone.

PMID- 29172964
TI  - Chronic Critical Illness in Adults #343.

PMID- 29172965
TI  - Risk assessment of toxic metals in marine sediments from the Arctic Ocean using a
      modified BCR sequential extraction procedure.
AB  - Surface sediment samples were collected from the Pacific sector of the Arctic
      Ocean during the 6th Chinese National Arctic Research Expedition (CHINARE), 2014.
      Concentrations and extractabilities of six toxic metals (Cd, Cr, Cu, Ni, Pb, and
      Zn) were determined using a modified sequential extraction procedure as described
      by the European Community Bureau of Reference (BCR). A new analytical hierarchy
      approach to risk assessment, involving sediment quality guidelines and risk
      assessment codes, is described for metals in marine sediments from the Arctic
      Ocean. Results indicate a mobility order of Pb > Cd > Cu > Zn > Ni > Cr with mean
      liable fraction (F1+F2+F3) being 83.0%, 81.6%, 62.0%, 47.1%, 42.1%, and 15.6%,
      respectively. Ni presents the most serious ecological risk in the study area,
      with most samples (93.9%) indicating medium risk, followed by Cu (54.5%) and Zn
      (27.3%). For Ni and Zn, there are also samples showing high ecological risk (Ni
      at site NB02, northern Bering Sea; Zn at R07, northern Chukchi Sea). The
      ecological risk for Cr indicates low ecological risk (93.9%) and some medium risk
      (6.1%). All Cd assessments indicate low ecological risk, while most Pb
      assessments indicate zero (33.3%) to low risk. The new ecological risk assessment
      method improves on assessments based on metal mobility or concentration alone.

PMID- 29172966
TI  - Antiquorum Sensing Activity of Seed Oils from Oleaginous Plants and Protective
      Effect During Challenge with Chromobacterium violaceum.
AB  - Seed oils from oleaginous plants are rich in fatty acids (FAs) that play
      important roles in the health of the consumers. Recent studies indicate that FA
      also can play an important role in communication and regulation of virulence in
      bacteria. Nevertheless, evidence demonstrating protection against bacterial
      infections mediated by their quorum sensing inhibition (QSI) activity is scarce.
      In this study, sunflower, chia, and amaranth oils, were assayed for their QSI
      capacity by inhibiting violacein production and alkaline exoprotease activity of
      Chromobacterium violaceum. In vitro assays revealed that the oils exhibited QSI
      activities, whereas in vivo they delayed death of mice inoculated
      intraperitoneally with the bacterium. Gas chromatography coupled with mass
      spectrometry analysis of the oils indicated the presence of saturated FA (SAFA)
      and unsaturated FA as main components. Through a structure-activity relationship
      study of free FAs, bactericidal effect was identified mainly for polyunsaturated
      FAs, whereas QSI activity was restricted to SAFA of chains 12-18 carbon atoms in
      length. These data correlate with a possible interaction suggested by molecular
      docking analysis of lauric, myristic, and stearic acids with the CviR protein.
      Our study highlights the antiquorum sensing potential of SAFA, which may be
      future antivirulence therapeutic agents for the treatment of bacterial
      infections.

PMID- 29172968
TI  - The sensitivity of soil enzymes, microorganisms and spring wheat to soil
      contamination with carfentrazone-ethyl.
AB  - Herbicides pose a significant threat to the natural environment, in particular in
      soils that are most exposed to plant protection agents. Prolonged herbicide use
      leads to changes in soil metabolism and decreases soil productive potential. In
      this study, the influence of carfentrazone-ethyl (CE) on the microbiological and
      biochemical properties of soil and the yield of Triticum aestivum L. was
      evaluated. Carfentrazone-ethyl was applied to sandy loam (pHKCl - 7.0) in doses
      of 0.000, 0.264, 5.280, 10.56, 21.18, 42.24, 84.48 and 168.96 ug kg-1 DM soil.
      Soil samples were subjected to microbiological and biochemical analyses on
      experimental days 30 and 60. Carfentrazone-ethyl disrupted the biological
      equilibrium in soil by decreasing the abundance and biodiversity of soil-dwelling
      microorganisms, the activity of soil enzymes, the values of the biochemical
      activity indicator and spring wheat yields. Carfentrazone-ethyl had the most
      adverse effects when applied in doses many fold higher than those recommended by
      the manufacturer. The toxic effects of CE were also determined by its soil
      retention time. Soil treated with CE was characterized by higher counts of
      oligotrophic bacteria, organotrophic bacteria, bacteria of the genus Azotobacter,
      actinomycetes and fungi on day 60, and spore-forming oligotrophic bacteria on day
      30. The activity of dehydrogenases, urease, alkaline phosphatase and beta
      glucosidase was higher on day 30 than on day 60.

PMID- 29172967
TI  - A comprehensive analysis of Italian web pages mentioning squalene-based influenza
      vaccine adjuvants reveals a high prevalence of misinformation.
AB  - Squalene-based adjuvants have been included in influenza vaccines since 1997.
      Despite several advantages of adjuvanted seasonal and pandemic influenza
      vaccines, laypeople's perception of such formulations may be hesitant or even
      negative under certain circumstances. Moreover, in Italian, the term "squalene"
      has the same root as such common words as "shark" (squalo), "squalid" and
      "squalidness" that tend to have negative connotations. This study aimed to
      quantitatively and qualitatively analyze a representative sample of Italian web
      pages mentioning squalene-based adjuvants used in influenza vaccines. Every
      effort was made to limit the subjectivity of judgments. Eighty-four unique web
      pages were assessed. A high prevalence (47.6%) of pages with negative or
      ambiguous attitudes toward squalene-based adjuvants was established. Compared
      with web pages reporting balanced information on squalene-based adjuvants, those
      categorized as negative/ambiguous had significantly lower odds of belonging to a
      professional institution [adjusted odds ratio (aOR) = 0.12, p = .004], and
      significantly higher odds of containing pictures (aOR = 1.91, p = .034) and being
      more readable (aOR = 1.34, p = .006). Some differences in wording between
      positive/neutral and negative/ambiguous web pages were also observed. The most
      common scientifically unsound claims concerned safety issues and, in particular,
      claims linking squalene-based adjuvants to the Gulf War Syndrome and autoimmune
      disorders. Italian users searching the web for information on vaccine adjuvants
      have a high likelihood of finding unbalanced and misleading material. Information
      provided by institutional websites should be not only evidence-based but also
      carefully targeted towards laypeople. Conversely, authors writing for non
      institutional websites should avoid sensationalism and provide their readers with
      more balanced information.

PMID- 29172969
TI  - Interleukin-35 Modulates the Imbalance Between Regulatory T Cells and T Helper 17
      Cells in Enterovirus 71-Induced Hand, Foot, and Mouth Disease.
AB  - Interleukin (IL)-35 modulates the imbalance between regulatory T cells (Tregs)
      and T helper (Th) 17 cells, which played vital roles in the pathogenesis of
      autoimmune and infectious diseases. However, the role of Tregs/Th17 cell
      imbalance and the regulatory functions of IL-35 have remained largely unknown in
      enterovirus 71 (EV71)-induced hand, foot, and mouth disease (HFMD). In this
      study, a total of 47 HFMD patients (30 with mild HFMD and 17 with severe HFMD)
      and 13 healthy individuals were enrolled. The frequencies of CD4+CD25+CD127dim/-
      Tregs and CD4+IL-17+ Th17 cells, as well as IL-35 expression levels, were
      measured. Cellular proliferation and cytokine production was also determined in
      purified Tregs following recombinant IL-35 stimulation. An imbalance between
      Tregs and Th17 cells was observed in children with severe HFMD, which manifested
      as a reduction in the Tregs population and an elevation in the Th17 population.
      Serum IL-35 concentrations were also decreased in case of severe HFMD, which
      correlated with the Tregs:Th17 cell ratios. Recombinant IL-35 stimulation
      increased the proportion of Tregs, but downregulated that of Th17 cells.
      Treatment with IL-35 enhanced Tregs suppressive function and IL-35 and IL-10
      expression, but reduced IL-22 secretion in both healthy individuals and those
      with severe HFMD. The Tregs:Th17 cell ratio was increased in the convalescent
      patients, however, a significant reduction in serum IL-35 was not observed. Our
      findings indicated that EV71 infection shifted the Tregs:Th17 cell ratio through
      IL-35 by downregulating inhibitory cytokine production and reducing the cell-to
      cell contact inhibition of effector T cells. Regulation of IL-35 as it relates to
      the Tregs/Th17 balance may play a critical role in the pathogenesis of EV71
      associated HFMD.

PMID- 29172970
TI  - Bayesian design for two-arm randomized Phase II clinical trials with endpoints
      from the exponential family using multiple constraints.
AB  - Frequentist design for two-arm randomized Phase II clinical trials with outcomes
      from the exponential dispersion family was proposed previously, where the total
      sample sizes are minimized under multiple constraints on the standard errors of
      the estimated group means and their difference. This design was generalized from
      an approach specific for dichotomous outcomes. The two previous approaches
      measure the central tendency of each group and treatment effect based on mean and
      difference in means. Other measures such as median or hazard ratio are more
      appropriate under certain situations. In addition, the frequentist approaches
      assume that unknown parameters are fixed values. This does not reflect the
      reality that uncertainty always exists for unknowns. Compared to the frequentist
      methods, the Bayesian approach offers a flexible way to measure central tendency
      and treatment effect, and incorporate uncertainty in parameters of interest into
      considerations. In this article, we generalize a Bayesian design for Phase II
      clinical trials with endpoints in the exponential family from the two previously
      developed frequentist approaches. The proposed design minimizes the total sample
      sizes under pre-specified constraints on the expected length of posterior
      credible intervals for measures of treatment effect and central tendency in each
      group. The design is applicable for trials with fixed or optimal randomization
      allocation ratio and can be applied under adaptive procedure. Examples of method
      implementations are provided for different types of endpoints from the
      exponential family in both fixed and adaptive settings.

PMID- 29172971
TI  - Physical Activity and Sedentary Behaviors Levels of Kuwaiti Adolescents: The
      Study of Health and Activity Among Adolescents in Kuwait.
AB  - BACKGROUND: There is only scarce number of studies available describing the
      lifestyle of adolescents living in Arab countries. Hence, we described physical
      activity (PA) and sedentary behaviors patterns among Kuwaiti adolescents and the
      associations with parental education. METHODS: Cross-sectional data from 435
      adolescents (201 boys and 234 girls) were collected from the Study of Health and
      Activity among Adolescents in Kuwait conducted between 2012 and 2013. Outcome
      variables included PA (ActiGraph GT1M accelerometers) and sedentary behaviors.
      Exposure variable was parental education. Descriptive and multiple logistic
      regression analyses were used to examine the association between parental
      education and outcome variables. RESULTS: Total sedentary time (minutes per day)
      was higher in girls [568.2 (111.6)] than in boys [500.0 (102.0)], whereas boys
      accumulated more minutes in light, moderate, and vigorous PA (all Ps <= .001). In
      total, 3.4% of adolescents spent >=60 minutes per day of moderate to vigorous PA
      (by accelerometry), while only 21% met the screen time guidelines. Low/medium
      maternal education was associated with a higher odds of exceeding screen time
      guidelines (odds ratio = 2.09; 95% confidence interval, 1.09-4.02). CONCLUSIONS:
      Most Kuwaiti adolescents in this sample were physically inactive and exceeded
      screen time guidelines. Objective PA was not socially patterned, yet an inverse
      association between maternal education and screen time behaviors was found.

PMID- 29172972
TI  - Choosing Doctors Wisely: Can Assisted Choice Enhance Patients' Selection of
      Clinicians?
AB  - We conducted a simulated clinician-choice experiment, comparing choices and
      decision-making processes of participants ( N = 688) randomized among four
      experimental arms: a conventional website reporting only quantitative performance
      information, a website reporting both qualitative (patient comments) and
      quantitative information, the second website augmented by a decision aid
      (labeling of patient comments), and the decision-aided website further augmented
      by the presence of a trained navigator. Introducing patient comments enhanced
      engagement with the quality information but led to a decline in decision quality,
      particularly the consistency of choices with consumers' stated preferences.
      Labeling comments helped erase the decline in decision quality, although the
      highest percentage of preference-congruent choices was seen in the navigator arm.
      Engagement with the quality information and satisfaction with choices available
      were likewise highest in the navigator arm. Findings held for high- and low
      skilled decision makers. Thus, navigator assistance may be a promising strategy
      for equitably promoting higher quality choices in information-rich contexts.

PMID- 29172973
TI  - Ezetimibe Use and LDL-C Goal Achievement: A Retrospective Database Analysis of
      Patients with Clinical Atherosclerotic Cardiovascular Disease or Probable
      Heterozygous Familial Hypercholesterolemia.
AB  - BACKGROUND: Ezetimibe is recommended by clinical practice guidelines as a second
      line therapy for lowering low-density lipoprotein cholesterol (LDL-C) levels, but
      little is known about its use and effectiveness in real-world populations.
      OBJECTIVE: To understand the real-world impact of adding or switching to
      ezetimibe on LDL-C goal achievement in patients with clinical atherosclerotic
      cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia
      (HeFH). METHODS: Patients aged >= 18 years with an LDL-C measurement available
      between January 1, 2013, and June 30, 2014, were identified using the Inovalon
      MORE 2 database; this included commercial, health insurance exchange, Medicare
      Advantage, and managed Medicaid patients. The index date was the date of the
      first LDL-C measurement. Patients were required to have evidence of clinical
      ASCVD or probable HeFH based on ICD-9-CM codes and >= 1 outpatient pharmacy claim
      for a statin in the 1-year pre-index period, as well as continuous medical and
      pharmacy coverage for 1 year pre- and post-index. Patients who added ezetimibe to
      existing statin therapy or switched to ezetimibe within 90 days post-index LDL-C
      measurement were identified in order to replicate the typical time a clinician
      takes to assess the use of ezetimibe. The primary outcome was the proportion of
      patients who met the LDL-C goal of < 70 mg/dL within the follow-up period. LDL-C
      goal achievement was evaluated by baseline LDL-C level groupings: < 70 mg/dL, 70
      99 mg/dL, 100-129 mg/dL, or >= 130 mg/dL; and across 4 patient diagnosis
      categories: all patients, ASCVD only, probable HeFH only, and ASCVD and probable
      HeFH. Descriptive analyses were reported. Categorical variables were summarized
      as the number of and corresponding percentage of patients. Continuous variables
      were presented as the mean and SD of the number of observations and median and
      range where appropriate. RESULTS: Of 125,330 patients who met selection criteria,
      mean age was 70.1 (SD = 9.9) years and mean LDL-C baseline was 90.7 (SD = 34.0)
      mg/dL. Over one half of patients (70%) were receiving statin therapy. Within the
      post-index time frame, 1.05% (n = 1,309) of patients added or switched to
      ezetimibe. Of these, 26% achieved LDL-C goal during the 90-day follow-up (59.5%
      did not achieve goal and 14.4% did not have a follow-up lab value). Therapeutic
      targets were reached by 30% of patients with baseline LDL-C levels of 70-99
      mg/dL; 14% of those with baseline LDL-C of 100-129 mg/dL; and 7% of those with
      baseline LDL-C of >= 130 mg/dL. Achievement of LDL-C goals also varied by
      baseline diagnosis category. CONCLUSIONS: The addition of or switch to ezetimibe
      therapy was associated with a relatively small percentage of LDL-C goal
      achievement (< 70 mg/dL) in patients with clinical ASCVD and/or HeFH, even among
      patients with baseline LDL-C between 70 and 99 mg/dL. To provide superior
      individualized care for patients with hyperlipidemia, there is a potential role
      for newer therapies in lipid lowering, such as PCSK9 inhibitors, in appropriate
      high-risk populations. DISCLOSURES: This study was sponsored by Amgen. Menzin,
      Yu, and Stern are employees of Boston Health Economics, which was contracted by
      Amgen to perform this study. Aggarwal is a former employee of Boston Health
      Economics. Boatman, Patel, and Harrison are employees and stockholders of Amgen.
      Study concept and design were contributed by Menzin, Aggarwal, Harrison, and
      Patel. Aggarwal, Stern, and Yu collected the data. Data interpretation was
      performed by Aggarwal, Harrison, Patel, and Boatman. The manuscript was written
      and revised primarily by Aggarwal, with assistance from the other authors.

PMID- 29172974
TI  - Following the Biosimilar Breadcrumbs: When Health Systems and Manufacturers
      Approach Forks in the Road.
AB  - : Over 2 years have passed since the first biosimilar was approved for use in the
      United States. Despite a relatively slow start, biosimilar activity has
      significantly increased in recent months. Biologics are the most expensive drug
      category in the United States, costing patients hundreds or even thousands of
      dollars per year. Biosimilars have the potential to significantly decrease cost
      of care, increase access, and improve patient outcomes. In order to realize the
      potential savings, biosimilar manufacturers, health care providers, and payers
      must develop strategies to navigate the challenging health care environment and
      understand where and how biosimilars bring the most value to patients. Trends in
      biosimilar uptake within health systems have demonstrated the need for
      manufacturers to deploy a robust product strategy before and after launch. In
      order to gain high-level insight from health system experiences with the first
      infliximab biosimilar approved in the United States, a questionnaire was
      distributed to pharmacy representatives from health systems during March and
      April 2017. Responses from more than 50 health systems across the country
      revealed that the key barriers and challenges faced with biosimilar uptake
      include payers and reimbursement, interchangeability, provider preference, and
      cost. This article explores health system experiences with biosimilars thus far
      and describes real-world implementation strategies. In addition, insights into
      manufacturer considerations are highlighted with regard to financial, clinical,
      and operational decisions. DISCLOSURES: The author received no outside funding
      support and has nothing to disclose.

PMID- 29172975
TI  - A Systematic Review of U.S. Biosimilar Approvals: What Evidence Does the FDA
      Require and How Are Manufacturers Responding?
AB  - BACKGROUND: Biosimilars undergo an abbreviated licensure pathway called 351(k),
      which was created by the Biologics Price Competition and Innovation Act of 2009.
      This approval process is different from the 351(a) pathway for original biologic
      approval and, as of August 2017, has been used to approve 5 biosimilars in the
      United States. OBJECTIVE: To identify the types and quantities of evidence
      required by the FDA for biosimilar approval and the corresponding evidence
      manufacturers have provided in their 351(k) biosimilar approval applications.
      METHODS: To collect data for this review, we searched through drug-specific FDA
      approval documents and approval-related FDA webcasts for approval indications and
      dates; reference product names; formulations; postmarketing requirements and
      commitments; evidence used for extrapolation claims; advisory committee votes;
      and evidence on similarity in analytical and functional characteristics,
      pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity.
      RESULTS: All biosimilars approved in the United States provided a large evidence
      base to demonstrate similarity in analytical and functional characteristics-3 to
      5 clinical studies showed similarity in pharmacokinetics and pharmacodynamics,
      and 1 to 2 clinical studies demonstrated efficacy. Safety and immunogenicity were
      evaluated across all clinical studies. All biosimilars were compared with either
      the U.S.-licensed reference product or the reference product licensed by the
      European Union. Extrapolation allowed biosimilars to be approved for indications
      in which clinical studies were not conducted. The few indications for which
      biosimilars did not share approval with the reference product were due to market
      exclusivity protection. None of the 5 biosimilars have been approved as
      interchangeable in the United States. CONCLUSIONS: The approval process for the
      first 5 biosimilars on the market in the United States provides a baseline
      understanding of what type and degree of evidence is required for biosimilar
      approval. DISCLOSURES: There was no external funding for this study. Hung reports
      employment as a pharmacist for CVS Health, an AHRQ F32 grant, and
      meeting/accommodation/travel support from AACP, DIA, and ISPOR, all outside the
      submitted work. Vu and Mostovoy have nothing to disclose. Study concept and
      design were contributed by Hung and Mostovoy, along with Vu. Hung and Vu
      collected the data, and data interpretation was performed primarily by Hung,
      along with Mostovoy. The manuscript was written by Hung and Vu and revised by all
      the authors. Some of the study results were previously presented as a poster at
      the ISPOR 22nd Annual International Meeting; May 20-24, 2017; in Boston,
      Massachusetts.

PMID- 29172976
TI  - Corrections.

PMID- 29172977
TI  - Conversion from Filgrastim to Tbo-filgrastim: Experience of a Large Health Care
      System.
AB  - BACKGROUND: In 2008, tbo-filgrastim was approved as a biosimilar in Europe and
      then approved in the United States by the FDA in 2012 as a biologic product with
      1 similar indication to filgrastim. Because tbo-filgrastim was less expensive
      than filgrastim, and clinical information and expert opinion supported
      similarity, the Pharmacy & Therapeutics Committee of a large health care system
      approved tbo-filgrastim as the preferred granulocyte-colony stimulating factor (G
      CSF) product in March 2014. OBJECTIVES: To (a) assess the use of filgrastim and
      tbo-filgrastim products by comparing baseline characteristics, setting of care,
      indication for use, and payer type and (b) understand potential barriers of
      conversion to tbo-filgrastim. METHODS: A retrospective evaluation of filgrastim
      and tbo-filgrastim use was conducted on all patients (N = 204) who received the
      drugs between July 2015 and December 2015 at the 2 largest hospitals in the
      health system. Baseline characteristics, indication requiring use of filgrastim
      or tbo-filgrastim, setting of care, and payer information were collected from
      electronic medical records, and descriptive analyses were conducted. RESULTS:
      Overall, G-CSFs were administered to 204 patients for 261 episodes of care
      (filgrastim and tbo-filgrastim were used in 65 and 196 episodes of care,
      respectively). Baseline characteristics were similar between the 59 patients who
      received filgrastim and the 174 patients who received tbo-filgrastim. G-CSF was
      primarily used in the inpatient setting (163 episodes of care, 63%) with 90% of
      patients using tbo-filgrastim. In the outpatient setting (98 episodes of care,
      38%), filgrastim and tbo-filgrastim were each used by 50% of patients. Tbo
      filgrastim was the preferred G-CSF by clinical providers for all indications,
      except for stem cell mobilization, where filgrastim use was higher (55% vs. 45%
      of 71 episodes of care). In the outpatient setting, analysis by payers showed
      that the majority of patients on commercial plans were using filgrastim (58%),
      while half of Medicare patients were using filgrastim (50%, n = 12). Twelve
      patients were self-paid, and all were using tbo-filgrastim. Subgroup analysis by
      hospital showed differences in utilization patterns. CONCLUSIONS: Although tbo
      filgrastim was the preferred G-CSF in our formulary, 29% of patients continued to
      receive filgrastim. Conversion to tbo-filgrastim has been largely successful, but
      extra steps may be needed to achieve full conversion to biosimilars. DISCLOSURES:
      No outside funding supported this study. Agboola was employed by Partners
      Healthcare at the time of the study. The authors have nothing to disclose. Study
      concept and design were contributed equally by Agboola and Reddy. Agboola
      collected the data, and data interpretation was performed by both authors. The
      manuscript was written primarily by Agboola, with assistance from Reddy. Both
      authors revised the manuscript.

PMID- 29172978
TI  - Application of the FDA Biosimilar Extrapolation Framework to Make Off-Label
      Determinations.
AB  - BACKGROUND: The FDA's extrapolation framework allows for a biosimilar to obtain
      licensure for indications that were not explicitly studied in the context of a
      clinical trial by extending conclusions from studies in 1 population to make
      inferences in other populations. Within routine clinical care, drugs and
      biologics are routinely used for medically accepted off-label indications. The
      appropriateness of these products for off-label indications are typically curated
      by compendia and guidelines, which have established processes and criteria for
      reviewing and evaluating the evidence to make such determinations. The evidence
      paradigm for biosimilars is different from originator biologics and is one of
      comparability to a reference product, not to reestablish clinical benefit. Thus,
      this paradigm shift can be applied to the exercise of making off-label
      determinations for biosimilars, and the FDA's framework of extrapolation can be
      used by clinicians and coverage policy decision makers to determine appropriate
      off-label indications for biosimilars. OBJECTIVE: To highlight how the FDA's
      biosimilar extrapolation framework can be used to make off-label policy
      decisions, using to 2 approved biosimilars for filgrastim and infliximab as case
      studies. METHODS: This study describes the FDA extrapolation framework for
      evaluating whether there are any differences in the mechanism of action,
      pharmacokinetics/biosdistribution, immunogenicity, and toxicity between on-label
      and off-label indications. Two case studies are presented that evaluate the
      biosimilars filgrastim-sndz and infliximab-dyyb for the offlabel indications of
      treating symptomatic anemia in patients with myelodysplastic syndromes and immune
      mediated colitis, respectively. The analytical, nonclinical, and clinical
      pharmacology, along with clinical studies demonstrating that filgrastim-sndz and
      infliximab-dyyb are biosimilar to their respective reference products, are
      reviewed and discussed in context with the extrapolation framework to ascertain
      whether use of the biosimilar within the off-label indications is scientifically
      justified. RESULTS: The mechanism of action of filgrastim and infliximab between
      their FDA-approved and off-label indications are the same. In addition, there is
      a high degree of similarity with the analytical and nonclinical characteristics
      of filgrastim-sndz and infliximab-dyyb and their respective reference products.
      There is no expectation of differences in safety and immunogenicity across the
      patient populations. Thus, some decision makers may determine that filgrastim
      sndz and infliximab-dyyb be used for the off-label indications of treating
      symptomatic anemia in patients with myelodysplasia and immune-mediated colitis,
      respectively. CONCLUSIONS: In some cases, the use of biosimilars for off-label
      indications can be scientifically justified. Since coverage policy decisions are
      intimately tied to compendia and guideline listings, it is incumbent upon these
      groups to conduct formal assessments of biosimilar off-label indications using
      the FDA extrapolation framework. DISCLOSURES: No outside funding supported this
      study. Li discloses that he has received honoraria and/or paid travel expenses as
      an advisory board and speaker's bureau participant for Pfizer; for speaking on
      behalf of Mylan and Apobiologix; and for participating on advisory boards for Eli
      Lilly and Mylan. Lobaina has nothing to disclose. Li was responsible for study
      design and manuscript revision. Li took the lead in data collection and
      interpretation and manuscript preparation, along with Lobaina.

PMID- 29172979
TI  - Pharmacovigilance of Biologics in a Multisource Environment.
AB  - : It is important that systems are in place to ensure that appropriate and
      comprehensive records are kept for use of all medications. It is fundamental to
      an effective pharmacovigilance system that patient medical records contain
      sufficient information to identify which medication has been prescribed, when it
      was administered, and at what dose. The availability of biologics from multiple
      sponsors has raised questions by some health care providers about the ability of
      current pharmacovigilance systems to trace specific biologics. In this article,
      periodic safety update reports were used to assess current postapproval safety
      monitoring for 3 biosimilars (epoetin alfa, somatropin, and filgrastim) that
      collectively represented nearly 350 million patient days of treatment worldwide.
      The reference products have each been marketed for over 10 years, forming a
      strong baseline of postmarketing safety data against which the safety of
      biosimilars can be compared. Published data from Denmark were also reviewed as
      additional evidence of how current pharmacovigilance systems are able to
      attribute adverse events to particular medicines. Collectively, the data show
      that spontaneous adverse drug reactions are reported by brand name in the
      majority of cases and are attributable to a specific medicine. Also discussed are
      the informational elements critical to monitoring biologics, or indeed any
      medicine, to ensure the availability of complete information so medicines that a
      patient has received can be quickly identified should a safety event occur. We
      support the addition of a single data element, the batch/lot number, to enhance
      the value of current pharmacovigilance systems. Adoption of 2-D barcodes in the
      European Union (EU) and standardized numerical identifiers in the United States
      addresses this need, since they include batch/lot numbers. These identifiers are
      already being implemented in the United States and the EU to improve patient
      safety, reduce medication errors, facilitate anticounterfeiting, and enable
      effective product recalls and adverse event reporting. Importantly, electronic
      identifiers will ameliorate safety reporting concerns with respect to
      biosimilars, while concurrently achieving these much broader public health
      objectives through more complete pharmacovigilance data. DISCLOSURES: This work
      was funded by Sandoz, a Novartis division. The authors were fully responsible for
      the content, editorial decisions, and opinions expressed in this article. No
      author received an honorarium related to the development of this manuscript. Sagi
      and Cohen are employees of Sandoz, and Woollett is an employee of Avalere Health.
      Study concept and design were contributed by Sagi and Woollett, along with Cohen.
      Data were primarily collected by Sagi, along with Woollett, and data
      interpretation was provided by all the authors. The manuscript was written by
      Woollett, along with Sagi and Cohen, and revised by Sagi and Cohen, along with
      Woollett.

PMID- 29172980
TI  - High-Cost Sarcoidosis Patients in the United States: Patient Characteristics and
      Patterns of Health Care Resource Utilization.
AB  - BACKGROUND: Sarcoidosis is a multisystem inflammatory disorder characterized by
      the presence of noncaseating granulomas in involved organs. Prior research has
      found that sarcoidosis imposes a significant economic burden to U.S. payers.
      However, the drivers of high health care costs among sarcoidosis patients are
      unknown. OBJECTIVE: To characterize sarcoidosis patients who were among the top
      20% of total health care costs. METHODS: Patients with a first diagnosis of
      sarcoidosis between January 1, 1998, and March 31, 2015 (index date) were
      selected from a deidentified privately insured administrative claims database.
      Study patients must have at least 12 months of continuous health plan enrollment
      prior to the index date. High-cost patients were those in the top 20% of total
      health care costs during the 12 months following the index date (follow-up
      period), and the remaining patients were classified as lower-cost patients.
      Patient characteristics, comorbidities, health care resource use, and health care
      costs in the study period were compared between the high-cost and lower-cost
      patients. Multiple logistic regression was used to assess the relationship
      between patient characteristics and being a high-cost sarcoidosis patient.
      RESULTS: A total of 7,173 sarcoidosis patients met the selection criteria. The
      20% of patients classified as high-cost patients accounted for approximately 72%
      of the total health care costs in the 12-month follow-up period. Compared with
      lower-cost patients, high-cost patients were slightly older (50.6 vs. 49.1 years)
      and had a higher comorbidity burden at baseline (Charlson Comorbidity Index = 1.8
      vs. 0.7). Mean annual total health care cost for high-cost sarcoidosis patients
      was 10 times that of their lower-cost counterparts ($73,345 vs. $7,073). Mean
      annual health care cost was $119,878 for patients in the 95th-99th percentile and
      $375,436 for patients in the top 1% of spend. High-cost patients had greater
      medical resource use and costs across all places of service (i.e., inpatient,
      emergency department, outpatient, and other) compared with lower-cost patients.
      Findings showed that higher total health care cost resulted in a larger
      proportion of inpatient spend and a smaller proportion of outpatient and pharmacy
      spend. Adjusting for baseline characteristics, high-cost patients were associated
      with a number of factors with high ORs: the presence of comorbidities such as
      deficiency anemia (OR = 1.606; P < 0.001), depression (OR = 1.504; P < 0.001), or
      cardiac arrhythmia (OR = 1.493; P < 0.001); having an inpatient admission (OR =
      9.771; P < 0.001); and use of biologic therapies adalimumab and/or infliximab (OR
      = 31.821; P < 0.001). CONCLUSIONS: This study described the characteristics of
      high-cost sarcoidosis patients and identified several high-cost indicators using
      contemporary administrative data. The health care cost distribution for
      sarcoidosis patients is highly skewed, making it a worthwhile endeavor to focus
      improvement efforts on patients in the top quintile. The study findings can help
      population health decision makers identify a subset of patients for targeted
      interventions aimed at improving quality of care and reducing overall costs.
      DISCLOSURES: This study was funded by Mallinckrodt Pharmaceuticals. Rice, White,
      and Lopez are employees of Analysis Group, which received funding from
      Mallinckrodt Pharmaceuticals to conduct this research. Nelson is an employee of
      Mallinckrodt Pharmaceuticals. Study concept and design were contributed by Rice,
      White, and Nelson, along with Lopez. Lopez took the lead in data collection, with
      assistance from Rice and White. Data interpretation was performed by all of the
      authors. The manuscript was written by Rice, Lopez, White, and Nelson and revised
      by Rice, along with White and Nelson.

PMID- 29172981
TI  - Biosimilar Products in the Modern U.S. Health Care and Regulatory Landscape.
AB  - : Biosimilars have the potential to greatly reduce medication costs in the United
      States. As of July 1, 2017, 5 biosimilars have been approved by the FDA, but only
      2 are available for purchase. This commentary outlines the efforts of an
      integrated health system to ensure biosimilar accessibility and discusses the
      current challenges and future implications. We highlight the implementation of a
      health plan policy and how a health system's formulary committee can encourage
      use while considering provider perceptions and operational challenges. In
      addition, we provide our perspective on potential implications for pricing, site
      of care, and pharmacy dispensing practices based on our experience with
      regulatory hurdles and market trends. Overall, we believe biosimilars are a good
      thing for the health care system, but their expected benefit may not be realized
      for years to come. DISCLOSURES: No outside funding supported this work. Affeldt
      reports advisory board membership with Janssen, and Skiermont reports membership
      with Amgen and McKesson. The other authors have nothing to disclose. Peterson and
      Budlong contributed the study concept and design and wrote the manuscript.
      Affeldt, Skiermont, Kyllo, and Heaton reviewed and revised the manuscript.

PMID- 29172982
TI  - Letter--A Challenge to the Pharmacy Profession to Raise Its Voice on Health Care
      Reform.
AB  - DISCLOSURES: Rubinstein provides consulting services to the pharmaceutical
      industry, health plans, employers, and specialty pharmacies and is a member of
      the editorial advisory board of Specialty Pharmacy News. He was a participant on
      the Amgen Biosimilar Report Advisory Board and reports consulting fees from
      Amgen.

PMID- 29172984
TI  - Assessment of RNA Stability in Postmortem Tissue from New-Born Lambs.
AB  - The recovery of high quality RNA from postmortem tissue is crucial to gene
      expression analyses. The acquisition of postmortem tissue has inherent time
      delays and, hence, understanding the temporal variation in the stability of total
      RNA is imperative. This experiment aimed: ( 1 ) to qualitatively and
      quantitatively assess the integrity of total RNA derived from a range of new-born
      ovine tissues (liver, spleen, thyroid, skeletal muscle, ileum, and perirenal
      adipose tissue) which were stored at ambient temperature until extraction at 0,
      3, 6, and 9 h postmortem; and ( 2 ) to analyze the stability of the reference
      gene(s) and expression of specific target genes in these tissues. Postmortem
      sampling time resulted in variable reductions in the relative integrity number
      (RIN) values across the tissues, ranging from 0.9 to 1.8% in liver, spleen,
      skeletal muscle, and ileum to 5.7-11.1% in the thyroid and perirenal adipose
      tissues, respectively (P < 0.05). In conclusion, tissues with small reductions in
      RIN value can exhibit disproportionately large differences in the normalization
      factor used to calculate the target gene expression. Hence, changes in transcript
      abundance due to RNA degradation are not always sufficiently buffered through
      normalization with reference genes. The normalization factor should be presented
      alongside the RIN value in postmortem tissue studies.

PMID- 29172983
TI  - A Comparison of Brand and Biosimilar Granulocyte-Colony Stimulating Factors for
      Prophylaxis of Chemotherapy-Induced Febrile Neutropenia.
AB  - BACKGROUND: Filgrastim-sndz, a granulocyte-colony stimulating factor (G-CSF), was
      introduced as a biosimilar to filgrastim in 2015, but real-world comparative
      effectiveness for filgrastim versus filgrastim-sndz has not been reported to
      date. OBJECTIVES: To (a) compare the incidence of febrile neutropenia for
      patients taking filgrastim versus those taking filgrastim-sndz and (b) compare
      the incidence of a potential serious adverse event for filgrastim versus
      filgrastim-sndz. METHODS: This retrospective cohort study identified patients
      receiving a G-CSF following chemotherapy, using administrative claims from the
      Humana Research Database. Patients enrolled in a Medicare Advantage Prescription
      Drug plan with a claim for a G-CSF from October 1, 2015, through September 30,
      2016, were identified. G-CSF use had to occur within 6 days of exposure to
      chemotherapy and without any subsequent chemotherapy within 14 days after G-CSF
      use. Febrile neutropenia requiring hospitalization was defined as hospitalization
      within 14 days after G-CSF use with (a) diagnosis of infection and/or neutropenia
      (broad definition) or (b) infection and neutropenia diagnoses (narrow
      definition). Serious adverse drug events (spleen rupture, acute respiratory
      syndrome, serious allergic reactions, capillary leak syndrome, thrombocytopenia,
      leukocytosis, cutaneous vasculitis, or bones and muscle ache) were also
      identified within 14 days after G-CSF use. An incidence difference of < 1% with
      90% CI crossing zero qualified as support for noninferiority. Two-tailed chi
      square tests were also used to investigate differences. RESULTS: A total of 88
      filgrastim and 101 filgrastim-sndz patients were identified. Filgrastim and
      filgrastim-sndz met the criteria for noninferiority based on an incidence
      difference of -0.6% (90% CI = -5.1%-4.0%; P = 0.84) for the broad definition of
      febrile neutropenia and a difference of -0.8% (90% CI = -3.8%-2.1%; P = 0.64) for
      the narrow definition. For the analysis of serious adverse events, an incidence
      difference of -2.5% (90% CI = -7.5%-2.5%; P = 0.42) for filgrastim compared with
      filgrastim-sndz was not sufficient to establish noninferiority. CONCLUSIONS: This
      study is one of the first analyses of real-world evidence regarding the
      noninferiority of filgrastim and filgrastim-sndz. The study results support
      noninferiority of filgrastim and filgrastim-sndz for prevention of febrile
      neutropenia requiring hospitalization. While noninferiority for serious adverse
      events was not supported, there was also no statistically significant difference
      between filgrastim and filgrastim-sndz. The study's small sample size could have
      limited the analysis of the relatively rare outcomes of febrile neutropenia
      requiring hospitalization and serious adverse events. A study including a larger
      numbers of patients taking filgrastim or filgrastim-sndz could provide additional
      insights. DISCLOSURES: This study received no outside funding. Douglas, Kennedy,
      and Slabaugh were employees of Humana Pharmacy Solutions at the time the study
      was conducted. Bowe, Schwab, and Lane were employees of Comprehensive Health
      Insights, a wholly owned subsidiary of Humana, at the time the study was
      conducted. Study concept and design were contributed by Douglas, Kennedy, Schwab,
      and Lane, along with Slabaugh and Bowe. Bowe took the lead in data collection,
      assisted by Schwab, and data interpretation was performed by Schwab, along with
      the other authors. The manuscript was written by Schwab, Lane, and Douglas and
      revised by Kennedy, Slabaugh, and Bowe, along with Schwab, Lane, and Douglas.

PMID- 29172985
TI  - Impact of desiccation and heat exposure stress on Salmonella tolerance to acidic
      conditions.
AB  - In a recent study, the pH of commonly used Salmonella pre-enrichment media became
      acidic (pH 4.0 to 5.0) when feed or feed ingredients were incubated for 24 h.
      Acidic conditions have been reported to injure or kill Salmonella. In this study,
      cultures of four known feed isolates (S. montevideo, S. senftenberg, S.
      tennessee, and S. schwarzengrund) and four important processing plant isolates
      (S. typhimurium, S. enteritidis, S. infantis, and S. heidelberg) were grown on
      meat and bone meal and later subjected to desiccation and heat exposure to stress
      the microorganism. The impact of stress on the isolates ability to survive in
      acidic conditions ranging from pH 4.0 to 7.0 was compared to the non-stressed
      isolate. Cell injury was determined on xylose lysine tergitol 4 (XLT4) and cell
      death determined on nutrient agar (NA). When measured by cell death in non
      stressed Salmonella, S. typhimurium was the most acid tolerant and S. heidelberg
      was the most acid sensitive whereas in stressed Salmonella, S. senftenberg was
      the most acid tolerant and S. tennessee was the most acid sensitive. The pH
      required to cause cell injury varied among isolates. With some isolates, the pH
      required for 50% cell death and 50% cell injury was similar. In other isolates,
      cell injury occurred at a more neutral pH. These findings suggest that the pH of
      pre-enrichment media may influence the recovery and bias the serotype of
      Salmonella recovered from feed during pre-enrichment.

PMID- 29172986
TI  - Bisphenol A and Bisphenol S release in milk under household conditions from baby
      bottles marketed in Italy.
AB  - A simple and sensitive validated analytical method based on liquid chromatography
      coupled to tandem fluorescence (FD) and ultraviolet (UV) spectrophotometry was
      applied to monitor the presence of bisphenol A and bisphenol S in plastic baby
      bottles marketed in Italy. The limits of detection (LOD) were 3.75 ng mL-1 and
      80.00 ng mL-1, and those of quantification (LOQ) were 12.51 ng mL-1 and 260.00 ng
      mL-1 for BPA (FD detection) and for BPS (UV detection), respectively. BPA was
      found in only four samples, two samples undergone to microwave heating and two
      samples undergone to bottle warmer heating either at 40 degrees C or at 80
      degrees C. Although the quantities of leached BPA were well below the reference
      dose for daily intake established by the European Food Safety Authority (EFSA)
      (4.0 ug kg-1 bw/day), the release of BPA and BPS from these plastic materials
      should be carefully considered by the government authorities to increase people's
      awareness on this issue and to protect the most vulnerable population group.

PMID- 29172988
TI  - The stratified win ratio.
AB  - The win ratio was first proposed in 2012 by Pocock and his colleagues to analyze
      a composite endpoint while considering the clinical importance order and the
      relative timing of its components. It has attracted considerable attention since
      then, in applications as well as methodology. It is not uncommon that some
      clinical trials require a stratified analysis. In this article, we propose a
      stratified win ratio statistic in a similar way as the Mantel-Haenszel stratified
      odds ratio, derive a general form of its variance estimator with a plug-in of
      existing or potentially new variance/covariance estimators of the number of wins
      for the two treatment groups, and assess its statistical performance using
      simulation studies. Our simulations show that our proposed Mantel-Haenszel-type
      stratified win ratio performs similarly to the Mantel-Haenszel stratified odds
      ratio for the simplified situation when the win ratio reduces to the odds ratio,
      and our proposed stratified win ratio is preferred compared to the inverse
      variance weighted win ratio and unweighted win ratio particularly when the data
      are sparse. We also formulate a homogeneity test following Cochran's approach
      that assesses whether the stratum-specific win ratios are homogeneous across
      strata, as this method is used frequently in meta-analyses and a better test for
      the win ratio homogeneity is not available yet.

PMID- 29172987
TI  - Claim MoreTM: Empowering African American Women to Make Healthy Choices.
AB  - Diabetes is a serious issue for African American women. The purpose of this
      project was to develop and test the feasibility of a culturally appropriate and
      faith-based healthy eating program for African American women at risk for
      developing diabetes. At total of 30 women from two churches completed a 12-week,
      faith-based program using a community-based approach with lay health educators in
      the church setting. Participants set healthy eating goals, attended weekly
      education classes, and received daily text messaging reminders related to their
      goals. Outcomes included high levels of social support, frequent engagement with
      the program, and improved healthy eating. This program demonstrated the ability
      to target African American women at risk for diabetes and engage them in a health
      related program.

PMID- 29172989
TI  - Association of Habitual Physical Activity With Cardiovascular Risk Factors and
      Target Organ Damage in Adolescents and Young Adults.
AB  - BACKGROUND: We aimed to (1) compare a subjective and objective measure of
      habitual physical activity (PA), (2) determine the association of PA and
      cardiovascular risk factors, and (3) test the hypothesis that PA is an
      independent determinant of target organ damage in youth. METHODS: Cross-sectional
      analysis of youth with and without type 2 diabetes [mean age = 22 (3.9) y]. PA
      was measured with International Physical Activity Questionnaire and Actical
      accelerometer. Target organ damage was assessed with echocardiography and
      peripheral arterial testing. Subjects were stratified into tertiles of total PA,
      and differences were tested by analysis of variance and chi2 tests. General
      linear models tested for independent associations. RESULTS: The correlation
      between International Physical Activity Questionnaire and accelerometry was weak
      (r = .23, P = .0003). Less active subjects had worse cardiovascular risk profiles
      and target organ damage, including stiffer arteries (P < .01). These outcome
      differences did not reach statistical significance when adjusted for covariates,
      such as lipid levels and glycemic control. CONCLUSION: Survey assessment of PA is
      complicated by inaccurate reporting. There is a strong association of habitual PA
      with cardiovascular risk factor clustering. PA may exert its beneficial effect on
      arterial stiffness in obese youth through improved glycemic control.

PMID- 29172990
TI  - Thresholds for infarction vary between gray matter and white matter in acute
      ischemic stroke: A CT perfusion study.
AB  - We aimed to investigate optimal perfusion thresholds defining ischemic core and
      penumbra for hemispheric-cortical gray matter (GM) and subcortical white matter
      (WM). A total of 65 sub-6 h ischemic stroke patients were assessed, who underwent
      acute computed tomography perfusion (CTP) and acute magnetic resonance imaging.
      CTP maps were generated by both standard singular value deconvolution (sSVD) and
      SVD with delay and dispersion correction (ddSVD). Analyses were undertaken to
      calculate sensitivity, specificity, and area under the curve (AUC) for each CTP
      threshold for core and penumbra in GM and WM. With sSVD, the core was best
      defined in GM by cerebral blood flow (CBF) < 30% (AUC: 0.73) and in WM by CBF <
      20% (AUC: 0.67). With ddSVD, GM core was best defined by CBF < 35% (AUC: 0.75)
      and in WM by CBF < 25% (AUC: 0.68). A combined GM/WM threshold overestimated core
      compared to diffusion-weighted imaging, CBF < 25% from sSVD (1.88 ml, P = 0.007)
      and CBF < 30% from ddSVD (1.27 ml, P = 0.011). The perfusion lesion was best
      defined by Tmax > 5 s (AUC: 0.80) in GM and Tmax > 7 s (AUC: 0.75) in WM. With
      sSVD, a delay time (DT) > 3 s from ddSVD was the optimal for both GM (AUC: 0.78)
      and WM (AUC: 0.75). Using tissue-specific thresholds for GM/WM provides more
      accurate estimation of acute ischemic core.

PMID- 29172991
TI  - Characterisation of HRas local signal transduction networks using engineered site
      specific exchange factors.
AB  - Ras GTPases convey signals from different types of membranes. At these locations,
      different Ras isoforms, interactors and regulators generate different biochemical
      signals and biological outputs. The study of Ras localisation-specific signal
      transduction networks has been hampered by our inability to specifically activate
      each of these Ras pools. Here, we describe a new set of site-specific tethered
      exchange factors, engineered by fusing the RasGRF1 CDC25 domain to sub
      localisation-defining cues, whereby Ras pools at specific locations can be
      precisely activated. We show that the CDC25 domain has a high specificity for
      activating HRas but not NRas and KRas. This unexpected finding means that our
      constructs mainly activate endogenous HRas. Hence, their use enabled us to
      identify distinct pathways regulated by HRas in endomembranes and plasma membrane
      microdomains. Importantly, these new constructs unveil different patterns of HRas
      activity specified by their subcellular localisation. Overall, the targeted GEFs
      described herein constitute ideal tools for dissecting spatially-defined HRas
      biochemical and biological functions.

PMID- 29172992
TI  - Cellular immunogenicity of human papillomavirus vaccines Cervarix and Gardasil in
      adults with HIV infection.
AB  - Human papillomavirus (HPV) infection is a frequent cause of malignant and non
      malignant disease, in particular among persons with HIV. HPV serotype-specific
      anti L1 antibodies protect against HPV infection but little is known about
      prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk
      individuals. We recently showed that both HPV vaccines (Gardasil(r) and
      Cervarix(r)) induce solid, serological immune responses in HIV-infected persons.
      This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV
      vaccine recipients, T cell responses being critical for B cell activation and
      antibody-isotype switching. Thirty HIV-infected patients on long-term
      antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or
      Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood
      mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour
      stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45)
      and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell
      sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and
      IFNgamma was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells
      (CD154+/IL-2+ or CD154+/ IFNgamma+) were determined. Both HPV-vaccines
      significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific
      immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after
      first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory
      despite HIV-induced immune compromisation.

PMID- 29172993
TI  - A Soup Service for Advanced Digestive Cancer Patients with Severe Anorexia in
      Palliative Care.
AB  - BACKGROUND/AIMS: The palliative care team (PCT), nutrition support team (NST),
      and department of nutrition in our hospital developed a special soup service for
      patients with terminal cancer. We evaluated the usefulness of this soup service
      for improving the mood in patients with advanced digestive cancer with severe
      anorexia. MATERIAL AND METHODS: We retrospectively reviewed the clinical data of
      18 patients with advanced cancer originating in digestive organs who received
      soup service at our institution between 2015 and 2016. Members of the PCT, NST,
      and a licensed cook visited the bedside of each patient and served them a cup of
      soup twice a week. RESULTS: Fifteen patients (83%) were able to taste the soup
      with no adverse events, and 11 (73%) of them enjoyed the taste of the soup. In
      the five patients who died in our hospital during the service, the time between
      their last soup intake and death ranged from two to seven days (median three
      days). CONCLUSION: Even terminally ill patients suffering from advanced digestive
      cancer with severe anorexia were able to enjoy the taste of the soup served to
      them. The establishment of special meal service, such as this soup service, may
      not only relieve their stress but also support the strength of living and help
      improve their spiritual quality of life.

PMID- 29172994
TI  - Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis
      in a phase 2 randomised controlled trial.
AB  - BACKGROUND: Recent basic and clinical evidence suggests amiloride may be
      neuroprotective in multiple sclerosis (MS) through the blockade of the acid
      sensing ion channel (ASIC). OBJECTIVE: To examine the neuroprotective efficacy of
      amiloride in acute optic neuritis (ON). METHODS: A total of 48 patients were
      recruited to a phase 2, double blind, single site, randomised controlled trial.
      Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and
      optical coherence tomography (OCT) and visual and electrophysiological measures
      were secondary outcome measures. Participants aged 18-55 years, <=28 days of
      onset of first episode unilateral ON, were randomised to amiloride (10 mg daily
      for 5 months) or placebo ( clinicaltrials.gov , NCT 01802489). RESULTS: Intention
      to-treat (ITT) cohort consisted of 43 patients; 23 placebo and 20 amiloride. No
      significant drug-related adverse events occurred. No significant differences were
      found in GDx ( p = 0.840). Visual evoked potentials (VEP) were significantly
      prolonged in the amiloride group compared to placebo ( p = 0.004). All other
      secondary outcome measures showed no significant difference. Baseline analysis of
      OCT data demonstrated a significant pre-randomisation thinning of ganglion cell
      layer. CONCLUSION: Amiloride has not demonstrated any neuroprotective benefit
      within this trial paradigm, but future neuroprotective trials in ON should target
      the window of opportunity to maximise potential neuroprotective benefit.

PMID- 29172995
TI  - PD-L1 blockade with avelumab: A new paradigm for treating Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer.
      Until recently, no durable treatment options were available for patients with
      advanced disease. As an immunogenic cancer, MCC was hypothesized to be a
      candidate for PD-L1/PD-1 targeted therapy. On March 23, 2017 the US Food and Drug
      Administration granted accelerated approval for avelumab, an anti-PD-L1
      monoclonal antibody, for the treatment of metastatic MCC on the basis of the
      JAVELIN Merkel 200 trial. Here we examine the results and implications of this
      pivotal study, published in Lancet Oncology by Kaufman et al., as well as current
      developments in the use of immune-checkpoint therapies for treating patients with
      MCC.

PMID- 29172996
TI  - Combination of the weighted kappa coefficients of two binary diagnostic tests.
AB  - The combination of two binary diagnostic tests in order to increase the accuracy
      of the diagnosis of a disease is a frequent procedure in clinical practice. When
      considering the losses associated with an erroneous classification with a binary
      diagnostic test, the parameter that is used to assess the diagnostic test is the
      weighted kappa coefficient. The weighted kappa coefficient depends on the
      sensitivity and the specificity of the diagnostic test, on the disease prevalence
      and on the weighting index. In this article, we study the combination of the
      weighted kappa coefficients of two binary diagnostic tests, defining the
      parameters and studying the conditions under which the combination of the two
      diagnostic tests increases the value of the weighted kappa coefficient of the
      combination. The Fieller method has been applied to obtain a confidence interval
      for the ratio between the combined weighted kappa coefficient and the weighted
      kappa coefficient of each diagnostic test. A program in R has been written to
      solve the problem studied and it is available as complementary material. The
      results have been applied to a real example.

PMID- 29172998
TI  - Establishment of H2Mab-119, an Anti-Human Epidermal Growth Factor Receptor 2
      Monoclonal Antibody, Against Pancreatic Cancer.
AB  - Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer
      and is associated with poor clinical outcomes. In addition, HER2 expression has
      been reported in other cancers, such as gastric, colorectal, lung, and pancreatic
      cancers. An anti-HER2 humanized antibody, trastuzumab, leads to significant
      survival benefits in patients with HER2-overexpressing breast cancers and gastric
      cancers. Herein, we established a novel anti-HER2 monoclonal antibody (mAb),
      H2Mab-119 (IgG1, kappa), and characterized its efficacy against pancreatic
      cancers using flow cytometry, Western blot, and immunohistochemical analyses.
      H2Mab-119 reacted with pancreatic cancer cell lines, such as KLM-1, Capan-2, and
      MIA PaCa-2, but did not react with PANC-1 in flow cytometry analysis. Western
      blot analysis also revealed a moderate signal for KLM-1 and a weak signal for MIA
      PaCa-2, although H2Mab-119 reacted strongly with LN229/HER2 cells. Finally,
      immunohistochemical analyses with H2Mab-119 revealed sensitive and specific
      reactions against breast and colon cancers but did not react with pancreatic
      cancers, indicating that H2Mab-119 is useful for detecting HER2 overexpression in
      pancreatic cancers using flow cytometry and Western blot analyses.

PMID- 29172997
TI  - Identification of ANXA2 (annexin A2) as a specific bleomycin target to induce
      pulmonary fibrosis by impeding TFEB-mediated autophagic flux.
AB  - Bleomycin is a clinically potent anticancer drug used for the treatment of germ
      cell tumors, lymphomas and squamous-cell carcinomas. Unfortunately, the
      therapeutic efficacy of bleomycin is severely hampered by the development of
      pulmonary fibrosis. However, the mechanisms underlying bleomycin-induced
      pulmonary fibrosis, particularly the molecular target of bleomycin, remains
      unknown. Here, using a chemical proteomics approach, we identify ANXA2 (annexin
      A2) as a direct binding target of bleomycin. The interaction of bleomycin with
      ANXA2 was corroborated both in vitro and in vivo. Genetic depletion of anxa2 in
      mice mitigates bleomycin-induced pulmonary fibrosis. We further demonstrate that
      Glu139 (E139) of ANXA2 is required for bleomycin binding in lung epithelial
      cells. A CRISPR-Cas9-engineered ANXA2E139A mutation in lung epithelial cells
      ablates bleomycin binding and activates TFEB (transcription factor EB), a master
      regulator of macroautophagy/autophagy, resulting in substantial acceleration of
      autophagic flux. Pharmacological activation of TFEB elevates bleomycin-initiated
      autophagic flux, inhibits apoptosis and proliferation of epithelial cells, and
      ameliorates pulmonary fibrosis in bleomycin-treated mice. Notably, we observe
      lowered TFEB and LC3B levels in human pulmonary fibrosis tissues compared to
      normal controls, suggesting a critical role of TFEB-mediated autophagy in
      pulmonary fibrosis. Collectively, our data demonstrate that ANXA2 is a specific
      bleomycin target, and bleomycin binding with ANXA2 impedes TFEB-induced
      autophagic flux, leading to induction of pulmonary fibrosis. Our findings provide
      insight into the mechanisms of bleomycin-induced fibrosis and may facilitate
      development of optimized bleomycin therapeutics devoid of lung toxicity.

PMID- 29172999
TI  - Left ventricular thrombus formation in patients undergoing femoral veno-arterial
      extracorporeal membrane oxygenation.
AB  - INTRODUCTION: Profoundly impaired left ventricular (LV) function in patients
      undergoing femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO)
      can result in intra-cardiac stasis and thrombus formation. There have been
      several attempts to improve LV unloading in patients with peripheral VA-ECMO,
      either by improving contractility or by venting the LV. METHODS: Data from all
      patients who underwent femoral VA-ECMO between 2007 and 2015 due to cardiogenic
      decompensation were retrospectively analysed regarding intra-cardiac thrombus
      formation. RESULTS: In total, 11 of 281 patients (3.91%) with femoral VA-ECMO
      developed an intra- or extra-cardiac thrombus despite adequate anticoagulation
      therapy. None of the patients survived this serious complication. CONCLUSION:
      Management strategies for patients with femoral VA-ECMO support and severely
      impaired LV function must be reassessed to avoid insufficient LV unloading at an
      early stage of ECMO therapy. Early LV decompression should be considered in
      patients with insufficient unloading of the LV to prevent intra-cardiac thrombus
      formation.

PMID- 29173000
TI  - The central dogma, "GMO" and defective epistemology.
AB  - The expression "Genetically Modified Organisms" was coined to indicate a group of
      agricultural products (mostly crops and vegetables), modified through direct DNA
      recombination in order to obtain useful phenotypic traits or to inhibit
      undesirable characteristics. But the border between rDNA ("GMO") and other
      biotech methods is blurred. Moreover, the ill-assorted group is frequently
      charged with having peculiar, negative characteristics: many activists, part of
      the public and a few social science scholars think that "GMOs" are all dubious,
      even inherently dangerous. However, theoretical justifications of this alleged
      problematic nature which is supposed to be necessarily linked to the "splicing"
      of DNA, only when applied to agricultural products, are missing: the only text
      which tries to go in depth on the subject, an article by biologist Barry
      Commoner, takes aim at the wrong target, misunderstanding the Central Dogma.
      "GMO" is a term that has no clear reference, let alone in a detrimental sense.
      The only attempt to give it epistemological dignity fails.

PMID- 29173001
TI  - Validating a research ethnicity questionnaire using genomic markers.
AB  - AIM: Population stratification is a confounding factor in genetic association
      studies. Self-report measures, the most common method of collecting ethnicity,
      may be less reliable for psychiatric patients. This study aims to validate our
      research ethnicity questionnaire as a reliable measure of genetic ancestry.
      METHODS: The validity of our questionnaire was compared with genetic ancestry
      according to structured association tests and dimensional reduction methods. Our
      research tool was also compared with a standard multiple choice questionnaire.
      RESULTS: Our research questionnaire was highly consistent with genetic ancestry.
      The standard questionnaire demonstrated a greater degree of inconsistency in
      identifying ethnicity. CONCLUSION: Collecting information on the geographical
      ancestry of each individual's grandparents provides a more comprehensive view of
      ethnicity to prevent population stratification and wasted finances on genotyping.

PMID- 29173002
TI  - miR-509-3p promotes cisplatin-induced apoptosis in ovarian cancer cells through
      the regulation of anti-apoptotic genes.
AB  - AIM: Previous observations have implicated miR-509-3p's ability in regulating
      cisplatin-triggered apoptosis in ovarian cancer. However, the underlying
      mechanisms were not fully understood. MATERIALS & METHODS: The roles of miR-509
      3p in cellular apoptosis were assessed through MTT and DAPI assays. The
      confirmation of the regulation of BCL2 family members by miR-509-3p was
      investigated by luciferase reporter assay, western blot, quantitative real-time
      PCR and rescue experiments. RESULTS: MiR-509-3p can decrease the IC50 values of
      cisplatin and promote apoptosis in ovarian cancer cells. Furthermore, on a panel
      of anti-apoptotic proteins, we identified that miR-509-3p could regulate BCL2,
      BCL2L2 and MCL1 via their 3'UTRs. CONCLUSION: Our study demonstrates that miR-509
      3p could sensitize ovarian cancer cells to cisplatin treatment by targeting
      multiple anti-apoptosis genes including BCL2.

PMID- 29173003
TI  - Life-threatening idiopathic reaction to hydrochlorothiazide treated with veno
      venous extracorporeal membrane oxygenation.
AB  - Hydrochlorothiazide has been shown to cause rare, but serious non-cardiogenic
      pulmonary edema. We present a case report of a patient with apparent septic shock
      and acute respiratory distress syndrome (ARDS) requiring life-sustaining veno
      venous extracorporeal membrane oxygenation (VV-ECMO). Upon further review of the
      literature and the chronology of the patient's presentation, her condition was
      most likely due to an immune-mediated reaction to hydrochlorothiazide. This
      represents the first case, to our knowledge, of such a severe reaction to
      hydrochlorothiazide supported with ECMO therapy.

PMID- 29173004
TI  - Advancing cancer drug development through precision medicine and innovative
      designs.
AB  - Precision medicine has been a hot topic in drug development over the last decade.
      Biomarkers have been proven useful for understanding the disease progression and
      treatment response in precision medicine development. Advancement of high
      throughput omics technologies has enabled fast identification of molecular
      biomarkers with low cost. Although biomarkers have brought many promises to drug
      development, steep challenges arise due to a large amount of data, complexity of
      technology, and lack of full understanding of biology. In this article, we
      discuss the technologies and statistical issues that are related to omics
      biomarker discovery. We also provide an overview of the current development of
      biomarker-enabled cancer clinical trial designs.

PMID- 29173005
TI  - Pharmacogenetics and psoriasis: is targeted treatment a possibility?

PMID- 29173007
TI  - Predictors and outcome of systemic lupus erythematosus (SLE) admission rates in a
      large teaching hospital in sub-Saharan Africa.
AB  - Although it was previously believed that systemic lupus erythematosus was
      uncommon among Africans, it has become increasingly apparent that the incidence
      is higher, and socioeconomic challenges such as physician shortages, poor medical
      facility access, and poor health literacy may worsen prognosis. This
      retrospective study examines characteristics and outcomes of hospitalized
      systemic lupus erythematosus patients over a two-year period and serves as a
      baseline for comparison for future studies to examine the outcomes with the
      provision of more dedicated care. There were 51 patient admissions over a two
      year period, with a mean duration from start of illness to admission of
      approximately two years. Duration of admission ranged from one to 140 days with a
      mean period of 26.12 days (SD +/- 26.6). There were 22 deaths (43.1% of
      admissions), which were mainly due to infections and renal complications. Factors
      associated with risk of death in regression analysis were: infections, fever,
      disease flare, musculoskeletal involvement, amenorrhea, depression, a clinical
      finding of hepatomegaly, and chest infection. Understanding the effect and
      outcome of systemic lupus erythematosus across different countries can elucidate
      the role of genetic, environmental, and other causative factors in the
      progression of the disease.

PMID- 29173006
TI  - Systematic analysis of ATG13 domain requirements for autophagy induction.
AB  - Macroautophagy/autophagy is an evolutionarily conserved cellular process whose
      induction is regulated by the ULK1 protein kinase complex. The subunit ATG13
      functions as an adaptor protein by recruiting ULK1, RB1CC1 and ATG101 to a core
      ULK1 complex. Furthermore, ATG13 directly binds both phospholipids and members of
      the Atg8 family. The central involvement of ATG13 in complex formation makes it
      an attractive target for autophagy regulation. Here, we analyzed known
      interactions of ATG13 with proteins and lipids for their potential modulation of
      ULK1 complex formation and autophagy induction. Targeting the ATG101-ATG13
      interaction showed the strongest autophagy-inhibitory effect, whereas the
      inhibition of binding to ULK1 or RB1CC1 had only minor effects, emphasizing that
      mutations interfering with ULK1 complex assembly do not necessarily result in a
      blockade of autophagy. Furthermore, inhibition of ATG13 binding to phospholipids
      or Atg8 proteins had only mild effects on autophagy. Generally, the observed
      phenotypes were more severe when autophagy was induced by MTORC1/2 inhibition
      compared to amino acid starvation. Collectively, these data establish the
      interaction between ATG13 and ATG101 as a promising target in disease-settings
      where the inhibition of autophagy is desired.

PMID- 29173009
TI  - Imaging patterns of gray and white matter abnormalities associated with PASAT and
      SDMT performance in relapsing-remitting multiple sclerosis.
AB  - OBJECTIVES: To map the regional patterns of white matter (WM) microstructural
      abnormalities and gray matter (GM) atrophy exclusively associated with reduced
      performance in the Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial
      Addition Test (PASAT) in relapsing-remitting (RR) multiple sclerosis (MS)
      patients. METHODS: In all, 177 RRMS patients and 80 healthy controls (HC) were
      studied. WM microstructural abnormalities were investigated on diffusion tensor
      images using tract-based spatial statistics analysis, and regional GM atrophy was
      estimated on three-dimensional (3D) T1-weighted images using voxel-based
      morphometry. RESULTS: Compared to HC, RRMS patients showed the expected pattern
      of cortical-subcortical GM atrophy and WM microstructural abnormalities. In
      patients, diffusivity abnormalities of supratentorial WM tracts correlated with
      both SDMT and PASAT scores. Lower SDMT performance was also associated with WM
      damage in several infratentorial WM tracts. Lower SDMT scores correlated with
      atrophy of the right anterior cingulate cortex, left postcentral gyrus, and right
      middle temporal gyrus, whereas lower PASAT scores correlated with atrophy of the
      deep GM nuclei, bilaterally, and several fronto-temporo-occipital regions.
      CONCLUSION: In RRMS patients, regional damage of different neural systems helps
      explaining reduced performance in SDMT and PASAT. WM microstructural damage
      typified reduced SDMT performance, whereas atrophy of several GM regions
      distinguished reduced PASAT performance.

PMID- 29173008
TI  - Monocyte-mediated chemotherapy drug delivery in glioblastoma.
AB  - AIM: To mechanistically prove the concept of monocyte-mediated nano drug delivery
      in glioblastoma (GBM). RESULTS: nano-doxorubicin-loaded monocytes (Nano-DOX-MC)
      were viable, able to cross an artificial endothelial barrier and capable of
      infiltrating GBM spheroids and releasing drug therein. GBM cells stimulated
      unloading of Nano-DOX-MC and took up the unloaded drug and released damage
      associated molecular patterns. In mice with orthotopic GBM xenografts, Nano-DOX
      MC resulted in much improved tumor drug delivery efficacy and damage-associated
      molecular patterns emission. Mechanistically, Nano-DOX was found sequestered in
      the lysosomal compartment and to induce autophagy, which may underlie MC's
      tolerance to Nano-DOX. Lysosomal exocytosis was found involved in the discharging
      mechanism of intracellular Nano-DOX. CONCLUSION: Nano-DOX can be effectively
      delivered by MC in GBM and induce cancer cell damage.

PMID- 29173010
TI  - Spiritual Well-Being, Depression, and Stress Among Hemodialysis Patients in
      Jordan.
AB  - PURPOSE: The spiritual dimension of a patient's life is an important factor that
      may mediate detrimental impacts on mental health. The lack of research
      investigating spiritual well-being, religiosity, and mental health among
      Jordanian hemodialysis patients encouraged this research. This study explored
      levels of spiritual well-being and its associations with depression, anxiety, and
      stress. DESIGN: A quantitative, cross-sectional correlational study. METHOD: A
      sample of 218 Jordanian Muslim hemodialysis patients completed a structured, self
      administered questionnaire. The data were analyzed using descriptive statistics
      and linear multivariate regression models. FINDINGS: The hemodialysis patients
      had, on average, relatively low levels of spiritual well-being, moderate
      depression, severe anxiety, and mild to moderate stress. The results of the
      regression models indicated that aspects of spiritual well-being were negatively
      associated with depression, anxiety, and stress, but only existential well-being
      consistently retained significant associations after controlling for religious
      well-being, religiosity, and sociodemographic variables. CONCLUSIONS: Greater
      spiritual and existential well-being of Jordanian hemodialysis patients were
      significantly associated with less depression, anxiety, and stress. It appears
      that these patients use religious and spiritual beliefs and practices as coping
      mechanisms to overcome their depression, anxiety, and stress. The implications
      for holistic clinical practice are explored.

PMID- 29173011
TI  - Genetic deletion of the Rho GEF Net1 impairs mouse macrophage motility and actin
      cytoskeletal organization.
AB  - Macrophages are innate immune cells that constantly patrol an organism to fulfill
      protective and homeostatic roles. Previous studies have shown that Rho GTPase
      activity is required for macrophage mobility, yet the roles of upstream
      regulatory proteins controlling Rho GTPase function in these cells are not well
      defined. Previously we have shown that the RhoA GEF Net1 is required for human
      breast cancer cell motility and extracellular matrix invasion. To assess the role
      of Net1 in macrophage motility, we isolated bone marrow macrophage (BMM)
      precursors from wild type and Net1 knockout mice. Loss of Net1 did not affect the
      ability of BMM precursors to differentiate into mature macrophages in vitro, as
      measured by CD68 and F4/80 staining. However, Net1 deletion significantly reduced
      RhoA activation, F-actin accumulation, adhesion, and motility in these cells.
      Nevertheless, similar to RhoA/RhoB double knockout macrophages, Net1 deletion did
      not impair macrophage recruitment to the peritoneum in a mouse model of sterile
      inflammation. These data demonstrate that Net1 is an important regulator of RhoA
      signaling and motility in mouse macrophages in vitro, but that its function may
      be dispensable for macrophage recruitment to inflammatory sites in vivo.

PMID- 29173013
TI  - Temporal compression in episodic memory for real-life events.
AB  - Remembering an event typically takes less time than experiencing it, suggesting
      that episodic memory represents past experience in a temporally compressed way.
      Little is known, however, about how the continuous flow of real-life events is
      summarised in memory. Here we investigated the nature and determinants of
      temporal compression by directly comparing memory contents with the objective
      timing of events as measured by a wearable camera. We found that episodic
      memories consist of a succession of moments of prior experience that represent
      events with varying compression rates, such that the density of retrieved
      information is modulated by goal processing and perceptual changes. Furthermore,
      the results showed that temporal compression rates remain relatively stable over
      one week and increase after a one-month delay, particularly for goal-related
      events. These data shed new light on temporal compression in episodic memory and
      suggest that compression rates are adaptively modulated to maintain current goal
      relevant information.

PMID- 29173012
TI  - Interleukin-6 Affects Aging-Related Changes of the PPARalpha-PGC-1alpha Axis in
      the Myocardium.
AB  - Aging is related to gradual increase of interleukin 6 (IL-6) plasma level that
      affects peroxisome proliferator-activated receptor (PPAR) expression. We
      evaluated age-related changes in cardiac expression of PPARalpha, its coactivator
      PGC-1alpha, and selected downstream proteins in mice with systemic IL-6 knockout
      (IL6KO). Male C57BL6/J wild-type (WT) and IL6KO mice were used at the age of 16
      20 weeks (young) and 24-30 months (senescent). Echocardiography and electron
      microscopy were applied to assess the function and ultrastructure of the heart.
      Western blotting and quantitative real-time PCR were used to estimate protein and
      mRNA levels of selected genes. PPARalpha expression in the myocardium of young
      IL6KO animals is lower and remains unchanged with aging, whereas in WT mice it
      declines with age and in both senescent groups it is equal. We observed aging
      related upregulation of PGC-1alpha and less pronounced decline of Sirt3 in IL6KO
      animals; the level of cytochrome C was significantly decreased in IL6KO group
      only, suggesting disturbed mitochondrial function, which was not sufficient to
      evoke obvious changes in cardiac performance and function assessed by
      echocardiography. IL-6 and aging are involved in regulation of PPARalpha and PGC
      1alpha expression and may influence the mitochondrial function.

PMID- 29173014
TI  - Initiation and completion rates of inactivated hepatitis A vaccination among
      children born between 2005 and 2014 in Zhejiang province, east China.
AB  - OBJECTIVES: To evaluate the initiation and completion and timeliness of
      inactivated hepatitis A vaccine (HAV-I) series, to identify the missed
      opportunities for HAV-I series, and to examine determinants associated with the
      completion of HAV-I. METHODS: Children born from 1 January 2005 to 31 December
      2014 and registered in Zhejiang provincial immunization information system
      (ZJIIS), were enrolled in this study. Descriptive statistics were used to
      describe the initiation and completion, the timeliness and the missed
      opportunities for HAV-I. Logistic regression analysis was applied to explore the
      determinants of the completeness of HAV-I. RESULTS: The initiation rate of HAV-I
      increased from 8.1% for the 2005 birth cohort to 13.2% for the 2014 birth cohort.
      The completion rate of HAV-I increased from 4.2% for the 2005 birth cohort to
      7.8% for the 2014 birth cohort. The timeliness rate of the 1st dose of HAV-I
      increased from 38.2% for the 2005 birth cohort to 57.9% for the 2014 birth
      cohort. The timeliness rate the 2nd dose of HAV-I increased from 17.3% for the
      2005 birth cohort to 35.3% for the 2014 birth cohort. 78.3% of the children who
      did not initiated any hepatitis A vaccine, had at least one immunization clinic
      visit after their 18th month of age. 36.0% of the children who received the 1st
      dose of HAV-I but did not receive the 2nd dose, had at least one immunization
      clinic visit after 6 months from the date of receiving the 1st dose of HAV-I. The
      determinants including year of birth, socio-economic development level of
      municipals, place of delivery, receipt of MMR/VarV were associated with the
      completion of HAV-I series. CONCLUSION: Although the initiation and completion of
      HAV-I series had improved in recent years, these indicators were still lower than
      those for other vaccines scheduled at the similar age. It is important for
      providers to identify every opportunity for HAV-I vaccination and to assure that
      children get protection from this vaccine-preventable disease.

PMID- 29173015
TI  - When Patients Tell Their Own Stories: A Meta-Narrative Study of Web-Based
      Personalized Texts of 214 Melanoma Patients' Journeys in Four Countries.
AB  - Malignant melanoma is an aggressive, recalcitrant disease. Its impact on people
      can be compounded by the physical and psychosocial consequences of medical
      management. Providing melanoma patients with patient-centered care that is
      effective, safe, and supportive throughout their journey requires knowledge of
      patients' progressive experiences and evolving perspectives. With ethical
      approval, we undertook a meta-narrative study of 214 experiential accounts of
      melanoma collected from the personal story sections of melanoma and cancer
      support websites. Using a narrative approach, we qualitatively examined the care
      experiences represented in these accounts and identified needs for supportive
      care in a framework reflective of the personal patient journey. We differentiate
      these across three key periods: lead-up to diagnosis; diagnosis, treatment, and
      recovery; and posttreatment and recurrence, and provide a visual representation
      of the patient journey. This article contributes to the growing body of work that
      utilizes Internet content as sources of qualitative, experiential health care
      data.

PMID- 29173016
TI  - Fast, asymmetric and nonhomogeneous clearance of SiC nanoaerosol assessed by
      micro-particle-induced x-ray emission.
AB  - AIM: To study the biopersistence of a silicon carbide (SiC) nanoaerosol in rat
      lungs, as time-dependent clearance and spatial distribution. MATERIALS & METHODS:
      Sprague-Dawley rats were exposed 6 h/day during 5 days to a SiC nanoaerosol at
      4.91 mg SiC/l. SiC biopersistence in rat lungs sections was assessed over 28 days
      by micro-particle-induced x-ray emission (MUPIXE) as 2D maps and by particle
      induced x-ray emission (PIXE) for whole-lung quantification. 2D maps were
      analyzed for SiC spatial distribution as skewness and kurtosis. RESULTS: Half
      time clearance was 10.9 +/- 0.9 days, agreeing with PIXE measurements. Spatial
      temporal analysis of SiC indicated decreased symmetry and homogeneity.
      CONCLUSION: Fast SiC clearance points that current nanoaerosol exposure may not
      be enough to trigger lung overload. Spatial distribution shows an asymmetric and
      nonhomogeneous SiC clearance.

PMID- 29173017
TI  - MYC leads the way.
AB  - Members of the MYC family of proto-oncogenes are the most commonly deregulated
      genes in all human cancers. MYC proteins drive an increase in cellular
      proliferation and facilitate multiple aspects of tumor initiation and
      progression, thereby controlling all hallmarks of cancer. MYC's ability to drive
      metabolic reprogramming of tumor cells leading to biomass accumulation and
      cellular proliferation is the most studied function of these oncogenes. MYC also
      regulates tumor progression and is often implicated in resistance to chemotherapy
      and in metastasis. While most oncogenic functions of MYC are attributed to its
      role as a transcription factor, more recently, new roles of MYC as a pro-survival
      factor in the cytoplasm suggest a previously unappreciated diversity in MYC's
      roles in cancer progression. This review will focus on the role of MYC in
      invasion and will discuss the canonical functions of MYC in Epithelial to
      Mesenchymal Transition and the cytoplasmic functions of MYC-nick in collective
      migration.

PMID- 29173019
TI  - 2017 TERMIS - Americas Conference & Exhibition Charlotte, NC December 3-6, 2017.

PMID- 29173022
TI  - Parametric modeling and optimal experimental designs for estimating isobolograms
      for drug interactions in toxicology.
AB  - In toxicology and related areas, interaction effects between two substances are
      commonly expressed through a combination index [Formula: see text] evaluated
      separately at different effect levels and mixture ratios. Often, these indices
      are combined into a graphical representation, the isobologram. Instead of
      estimating the combination indices at the experimental mixture ratios only, we
      propose a simple parametric model for estimating the underlying interaction
      function. We integrate this approach into a joint model where both the parameters
      of the dose-response functions of the singular substances and the interaction
      parameters can be estimated simultaneously. As an additional benefit, this
      concept allows to determine optimal statistical designs for combination studies
      optimizing the estimation of the interaction function as a whole. From an optimal
      design perspective, finding the interaction parameters generally corresponds to a
      [Formula: see text]-optimality resp. [Formula: see text]-optimality design
      problem, while estimation of all underlying dose response parameters corresponds
      to a [Formula: see text]-optimality design problem. We show how optimal designs
      can be obtained in either case as well as how combination designs providing
      reasonable performance in regard to both criteria can be determined by putting a
      constraint on the efficiency in regard to one of the criteria and optimizing for
      the other. As all designs require prior information about model parameter values,
      which may be unreliable in practice, the effect of misspecifications is
      investigated as well.

PMID- 29173023
TI  - Erratum.

PMID- 29173018
TI  - Formation of pollen apertures in Arabidopsis requires an interplay between male
      meiosis, development of INP1-decorated plasma membrane domains, and the callose
      wall.
AB  - In most plant species, surfaces of pollen grains display characteristic patterns
      of apertures, formed by the gaps in the pollen wall exine. The aperture patterns
      are species-specific and tend to be very precise, with pollen of each species
      usually developing a certain number of apertures placed at distinct positions and
      acquiring specific morphology. The precision with which pollen apertures are
      produced suggests that developing pollen grains possess robust mechanisms that
      allow them to specify particular membrane domains as the future-aperture sites
      and to protect these sites from exine deposition. Recently, we demonstrated that
      formation of apertures in Arabidopsis depends on certain membrane domains
      attracting a novel protein, INP1, that assembles into punctate lines and helps to
      anchor these membrane domains to the overlying callose wall. Here we show that in
      the absence of male meiosis the ability of INP1 to assemble into lines at the
      pollen surface is compromised. However, INP1 still arrives to the pollen surface
      and mediates the interactions between the plasma membrane and the callose wall,
      potentially contributing to the formation of grossly abnormal patterns on pollen
      surface.

PMID- 29173025
TI  - Functional nanocarrier for drug and gene delivery via local administration in
      mucosal tissues.
AB  - Local administration has many advantages for treating diseases. However, the
      surface mucus layer becomes a major obstacle that easily traps and fast removes
      local administrated drugs and genes in mucosal tissues. Fortunately, the rapidly
      developing nanocarriers with special physical and chemical properties may help to
      refine the treatment of mucosal tissues via delivering drugs and genes to the
      target tissue, and prolong the drug action time. Therefore, this review focuses
      on the strategies to apply different nanocarriers for drug-delivery in mucosal
      tissues, including mucoadhesive and mucus-penetrating types. Delivering drugs and
      genes to anatomical sites with high mucus turnover becomes more feasible and
      effective, and maintains sufficient local drug concentration to improve treatment
      efficacy.

PMID- 29173026
TI  - Consistency ensured test strategies for supportive evidence of treatment efficacy
      in noninferiority clinical trials.
AB  - Noninferiority (NI) clinical trials are designed to demonstrate that a new
      treatment is not unacceptably worse than an active control on a clinically
      meaningful endpoint. While such an endpoint can be of any type, the focus of this
      manuscript is on the binary-type endpoint. Examples of this endpoint can be
      clinical cure endpoint for patients with bacterial diseases or based on a pre
      specified virological threshold for viral diseases. However, in addition to
      assessing such a binary endpoint for the NI comparison, the trial may also
      evaluate a second clinically relevant endpoint for providing additional support
      to the evidence of the designated primary endpoint. Specifically, if the trial is
      successful in demonstrating statistical significance on the first endpoint, then
      observing at least a positive trend in efficacy on the second endpoint may
      provide additional supportive evidence of efficacy. The second endpoint can be a
      time-to-event type endpoint, such as time-to-symptom resolution (TSR) or time to
      all-cause mortality for infectious disease trials, time-to-wound closure for
      wound healing trials, or other endpoints. We propose two consistency ensured test
      strategies for the two hypotheses of a trial, one associated with the binary
      endpoint and the other with the second endpoint, both with the objective of
      drawing inference regarding the efficacy of the new treatment based on findings
      from testing the two hypotheses. A key feature of these test strategies is that
      basically it does not require multiplicity adjustment of the significance levels.
      We conclude with general discussion of the testing methods and possible
      applications to unmet medical need trials.

PMID- 29173024
TI  - Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of
      ovarian cancer by down-regulating MMP2 and MMP9.
AB  - Ovarian cancer is the third most common cancer in the female reproductive organs
      and epithelial ovarian cancer has the highest lethality of all gynecological
      cancers. Pomegranate fruit juice (PFJ) has been shown to inhibit the growth of
      several types of cancer other than ovarian cancer. In this study, we exposed the
      ovarian cancer cell line A2780 to PFJ and two of its components (ellagic acid and
      luteolin). MTT and wound healing assays demonstrated that all three treatments
      suppressed the proliferation and migration of the ovarian cancer cells. In
      addition, western blotting and ELISA assays showed that the expression levels of
      MMP2 and MMP9 gradually decreased after treatment with increasing concentrations
      of ellagic acid and luteolin. To confirm our findings in the in vitro
      experiments, we used another ovarian cancer cell line, ES-2, in nude mice
      experiments. All three treatments inhibited tumor growth without obvious side
      effects. Furthermore, compared with the control group, the expression levels of
      MMP2 and MMP9 were depressed. Ellagic acid induced a greater effect than
      luteolin, suggesting that ellagic acid might be a promising candidate for further
      preclinical testing for treatment of human ovarian cancer.

PMID- 29173027
TI  - Cross-cultural differences in item and background memory: examining the influence
      of emotional intensity and scene congruency.
AB  - After viewing a scene, individuals differ in what they prioritise and remember.
      Culture may be one factor that influences scene memory, as Westerners have been
      shown to be more item-focused than Easterners (see Masuda, T., & Nisbett, R. E.
      (2001). Attending holistically versus analytically: Comparing the context
      sensitivity of Japanese and Americans. Journal of Personality and Social
      Psychology, 81, 922-934). However, cultures may differ in their sensitivity to
      scene incongruences and emotion processing, which may account for cross-cultural
      differences in scene memory. The current study uses hierarchical linear modeling
      (HLM) to examine scene memory while controlling for scene congruency and the
      perceived emotional intensity of the images. American and East Asian participants
      encoded pictures that included a positive, negative, or neutral item placed on a
      neutral background. After a 20-min delay, participants were shown the item and
      background separately along with similar and new items and backgrounds to assess
      memory specificity. Results indicated that even when congruency and emotional
      intensity were controlled, there was evidence that Americans had better item
      memory than East Asians. Incongruent scenes were better remembered than congruent
      scenes. However, this effect did not differ by culture. This suggests that
      Americans' item focus may result in memory changes that are robust despite
      variations in scene congruency and perceived emotion.

PMID- 29173028
TI  - Easy Debonding of Ceramic Brackets Bonded with a Light-Cured Orthodontic Adhesive
      Containing Microcapsules with a CO2 Laser.
AB  - OBJECTIVE: An easy debonding method for ceramic brackets using a light-cured Bis
      GMA resin containing heat-expandable microcapsules and CO2 laser was
      investigated. BACKGROUND: Ceramic brackets are used frequently in orthodontic
      treatment because of their desirable esthetic properties. However, the
      application of heavy force to ceramic brackets in debonding can fracture the
      tooth enamel and ceramic brackets, causing tooth pain. MATERIALS AND METHODS: In
      total, 60 freshly extracted bovine permanent mandibular incisors were divided
      randomly into 10 groups of 6 specimens each, corresponding to the number of
      variables tested. Ceramic brackets were bonded to bovine permanent mandibular
      incisors using an orthodontic bonding agent containing heat-expandable
      microcapsules at different levels (0-30 wt%) and resin composite paste, and cured
      by a curing device. The bond strengths were measured before and after CO2 laser
      irradiation, and the temperature increase in the pulp chamber in fresh human
      first premolars was also evaluated. RESULTS: With CO2 laser irradiation for 5 sec
      to the bracket, the bond strength in the 25% microcapsule group decreased
      significantly, to ~0.17-fold, compared with that of the no-laser group (p <
      0.05). The maximum temperature increase in the pulp chamber was 5.3 degrees C
      with laser irradiation, which was less than the level that induces pulp damage.
      CONCLUSIONS: From these results, it seems likely that the combined use of a light
      cured orthodontic bonding agent containing microcapsules and a CO2 laser is a
      simple debonding system for ceramic brackets, with less debonding time and enamel
      damage.

PMID- 29173029
TI  - Enzymatically synthesized megalo-type isomaltosaccharides enhance the barrier
      function of the tight junction in the intestinal epithelium.
AB  - Megalo-type isomaltosaccharides are an enzymatically synthesized foodstuff
      produced by transglucosylation from maltodextrin, and they contain a mid-chain
      length polymer of D-glucose with alpha-1,6-glycoside linkages. The injection of a
      solution of megalo-type isomaltosaccharides (1-4%(w/v), average DP = 12.6), but
      not oligo-type isomaltosaccharides (average DP = 3.3), into the intestinal lumen
      dose-dependently reduced the transport rates of tight junction permeable markers
      in a ligated loop of the anesthetized rat jejunum. Application of the
      megalosaccharide also suppressed the transport of tight junction markers and
      enhanced transepithelial electrical resistance (TEER) in Caco-2 cell monolayers.
      Cholesterol sequestration by methyl-beta-cyclodextrin in the Caco-2 monolayers
      abolished the effect of megalosaccharide. Treatment with anti-caveolin-1 and a
      caveolae inhibitor, but not clathrin-dependent endocytosis and macropinocytosis
      inhibitors, suppressed the increase in TEER. These results indicate that
      isomaltosaccharides promote the barrier function of tight junctions in the
      intestinal epithelium in a chain-length dependent manner and that caveolae play a
      role in the effect.

PMID- 29173030
TI  - A Summary of Pediatric Palliative Care Team Structure and Services as Reported by
      Centers Caring for Children with Cancer.
AB  - BACKGROUND: Little is known about the composition, availability, integration,
      communication, perceived barriers, and work load of pediatric palliative care
      (PPC) providers serving children and adolescents with cancer. OBJECTIVE: To
      summarize the structure and services of programs to better understand successes
      and gaps in implementing palliative care as a standard of care. METHODS: Cross
      sectional online survey about the palliative care domains determined by the
      Psychosocial Care of Children with Cancer and Their Families Workgroup. SUBJECTS:
      A total of 142 surveys were completed with representation from 18 countries and
      39 states. RESULTS: Three-fourths of sites reported having a PPC program
      available for the pediatric cancer population at their center. Over one-fourth
      (28%) have been in existence less than five years. Fewer than half of sites (44%)
      offered 24/7 access to palliative care consultations. Neither hospital-based nor
      local community hospice services were available for pediatric patients at 24% of
      responding sites. A specific inpatient PPC unit was available at 8% of sites.
      Criteria for automatic palliative referrals ("trigger" diagnoses) were reported
      by 44% respondents. The presence of such "triggers" increased the likelihood of
      palliative principle introduction 3.41 times (p < 0.003). Six percent of
      respondents perceived pediatric oncology patients and their families "always"
      were introduced to palliative care concepts and 17% reported children and
      families "always" received communication about palliative principles. The most
      prevalent barriers to palliative care were at the provider level. DISCUSSION:
      Children and adolescents with cancer do not yet receive concurrent palliative
      care as a universal standard.

PMID- 29173031
TI  - Probing the interaction of silver nanoparticles with tau protein and
      neuroblastoma cell line as nervous system models.
AB  - Interestingly pharmaceutical sciences are using nanoparticles (NPs) to design and
      develop nanomaterials-based drugs. However, up to recently, it has not been well
      realized that NPs themselves may impose risks to the biological systems. In this
      study, the interaction of silver nanoparticles (AgNPs) with tau protein and SH
      SY5Y neuroblastoma cell line, as potential nervous system models, was examined
      with a range of techniques including intrinsic fluorescence spectroscopy,
      circular dichroism (CD) spectroscopy, 3-(4,5-dimethylthiazol-2-Yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, and acridine orange/ethidium bromide
      (AO/EB) dual staining method. Fluorescence study showed that AgNPs with a
      diameter of around 10-20 nm spontaneously form a static complex with tau protein
      via hydrogen bonds and van der Waals interactions. CD experiment revealed that
      AgNPs did not change the random coil structure of tau protein. Moreover, AgNPs
      showed to induce SH-SY5Y neuroblastoma cell mortality through fragmentation of
      DNA which is a key feature of apoptosis. In conclusion, AgNPs may induce slight
      changes on the tau protein structure. Also, the concentration of AgNPs is the
      main factor which influences their cytotoxicity. Since, all adverse effects of
      NPs are not well detected, so probably additional more specific testing would be
      needed.

PMID- 29173033
TI  - Evaluation of Alzheimer's disease progression based on clinical dementia rating
      scale with missing responses and covariates.
AB  - In clinical trials, patient's disease severity is usually assessed on a Likert
      type scale. Patients, however, may miss one or more follow-up visits (non
      monotone missing). The statistical analysis of non-Gaussian longitudinal data
      with non-monotone missingness is difficult to handle, particularly when both
      response and time-dependent covariates are subject to such missingness. Even when
      the number of patients with intermittent missing data is small, ignoring those
      patients from analysis seems to be unsatisfactory. The focus of the current
      investigation is to study the progression of Alzheimer's disease by incorporating
      a non-ignorable missing data mechanism for both response and covariates in a
      longitudinal setup. Combining the cumulative logit longitudinal model for
      Alzheimer's disease progression with the bivariate binary model for the missing
      pattern, we develop a joint likelihood. The parameters are then estimated using
      the Monte Carlo Newton Raphson Expectation Maximization (MCNREM) method. This
      approach is quite easy to handle and the convergence of the estimates is attained
      in a reasonable amount of time. The study reveals that apolipo-protein plays a
      significant role in assessing a patient's disease severity. A detailed simulation
      has also been carried out for justifying the performance of our approach.

PMID- 29173032
TI  - Impact of SNP-SNP interaction among ABCB1, ARRB2, DRD1 and OPRD1 on methadone
      dosage requirement in Han Chinese patients.
AB  - AIM: To evaluate the potential association of the genetic polymorphisms in ABCB1,
      ARRB2, DRD1 and OPRD1 genes with methadone dosage requirement among Han Chinese
      opioid-dependent patients. MATERIALS & METHODS: Eight SNPs in ABCB1, ARRB2, DRD1
      and OPRD1 genes were selected and genotyped using Sequenom MassARRAY platform
      among 257 methadone maintenance treatment patients. The required information
      about stable methadone dose, urine analysis for opioid and socio-demographic
      characteristics was collected. Generalized multifactor dimensionality reduction
      method was performed to analyze the SNP-SNP interaction. RESULTS: We found that
      patients carrying the rs529520TG genotype of OPRD1 probably required higher
      methadone treatment dosage. A 3-locus SNP-SNP interaction pattern (rs1128503 in
      ABCB1, rs529520 in OPRD1 and rs1045280 in ARRB2) was significantly associated
      with the methadone dosage requirement (p = 0.029). CONCLUSION: Our results
      suggested that specific OPRD1 variants and interaction among polymorphisms in
      ABCB1, OPRD1 and ARRB2 genes contributes to methadone dosage requirement in Han
      Chinese opioid-dependent patients.

PMID- 29173034
TI  - Improved petroleum refinery wastewater treatment and seawater desalination
      performance by combining osmotic microbial fuel cell and up-flow microbial
      desalination cell.
AB  - The petroleum refinery wastewater which is a product of petroleum refinery has a
      high organic content. This study explores the utilization of petroleum refinery
      wastewater collected from petroleum refinery as a resource for bioelectricity
      generation and using this energy for salt removal from seawater in a
      hydraulically connected osmotic microbial fuel cell (OsMFC) and up flow microbial
      desalination cell (UMDC). Anaerobic mixed sludge was used in the anodic chamber
      of OsMFC and UMDC. Petroleum refinery wastewater was fed first into the OsMFC and
      then transferred to the UMDC. The OsMFC and UMDC were connected to 1000 and 100
      Omega external resistance respectively. Experimental results showed that the
      combined system could remove 93% of chemical oxygen demand (COD) from the
      petroleum refinery wastewater whilst 48% salts were removed from the seawater.
      Experimental results showed that this complex wastewater can be treated and
      produce bioelectricity, with COD removal and salt removal. The hydraulically
      connected OsMFC and up flow MDC provide a suitable platform for wastewater
      treatment and seawater desalination.

PMID- 29173036
TI  - Determination and health risk assessment of enrofloxacin, flumequine and
      sulfamethoxazole in imported Pangasius catfish products in Thailand.
AB  - The goals of this study were to determine the levels of three antibiotics -
      enrofloxacin, flumequine and sulfamethoxazole - in Pangasius catfish products
      imported into Thailand and to assess the health risks from consumption. To
      extract these antibiotic residues, acetonitrile, methanol and a small amount of
      formic acid were used as solvents. Determination of the antibiotics after
      extraction steps was carried out by liquid chromatography coupled with tandem
      mass spectrometry (LC-MS/MS) technique. The results showed that 14 and 3 samples
      of Pangasius catfish products were contaminated with enrofloxacin and
      sulfamethoxazole, respectively. No flumequine residue was found. While the
      concentration levels of these antibiotics in most contaminated samples were lower
      than the European Union (EU) standard, one sample was found to contain
      sulfamethoxazole at 245.91 ug kg-1, which was higher than the EU standard (100 ug
      kg-1), indicating the likelihood that some contaminated freshwater fish products
      are widely distributed in Thai markets. Notably, the concentration levels of
      enrofloxacin in samples of Pangasius catfish with skin were higher than in non
      skin products, suggesting that products with skin might retain more antibiotic
      residues than non-skin products. Although the hazard quotient showed that
      consuming imported Pangasius catfish products, based on the current consumption
      rate, will not adversely affect consumer health, antibiotic residues in Pangasius
      catfish products imported into Thailand should be continually monitored.

PMID- 29173037
TI  - Can Women Facilitate Men's Prostate Cancer Screening Informed Decision-Making?
      The M-PACT Trial.
AB  - The M-PACT study compared an all-male with a mixed-sex intervention to increase
      informed decision-making for prostate cancer screening among African-American men
      in church settings. We recruited 262 men in 18 churches randomized to the two
      intervention approaches. Trained and certified lay peer community health advisors
      in each church led a series of four men's health workshops on informed decision
      making for prostate cancer screening. African-American male workshop participants
      completed baseline, post-workshop, and 12-month follow-up surveys. Contrary to
      our expectations, including women in the workshops did not result in increased
      intervention efficacy for the informed decision-making outcomes as both groups
      showed significant improvement over time in several study outcomes including
      stage of decision-making for prostate cancer screening, preference for role in
      decision-making, prostate cancer knowledge, and self-reports of prostate specific
      antigen testing. Finally, men who attended multiple workshops had better informed
      decision-making outcomes on several indicators. The current findings suggest
      mixed results from including women in this men's health educational intervention.
      Future work should consider optimal ways of providing family support for African
      American men's health promotion.

PMID- 29173038
TI  - State of the art of the environmental behaviour and removal techniques of the
      endocrine disruptor 3,4-dichloroaniline.
AB  - In recent years, the presence of Endocrine Disrupting Chemicals (EDCs) in
      wastewater discharges from agricultural and industrial sources, [1] fresh- and
      estuarine-waters, as well as soils, has been reported in the literature. [2]
      Studies of adverse changes in wildlife, linked to environmental exposure to these
      substances, and the suggestion that humans could also be at similar risk of
      adverse health effects, [3-5] have raised concern for urgent action to understand
      and reduce such risks. 3,4-Dichloroaniline (3,4-DCA) has been recognized as an
      EDC, with regards to endocrine disruption data for both wildlife populations and
      human health. [5] 3,4-DCA is present in the environment as a product of the
      biodegradation of phenylurea and phenylcarbamate pesticides [6,7] ; furthermore,
      it can be introduced from industrial and municipal wastewater that is
      insufficiently purified, or via accidental spills. [8-10] Increasing
      concentrations of 3,4-DCA in soil and water are the result of its high
      persistence and accumulation, as well as its low biodegradability. [11,12] Hence,
      remediation techniques require in-depth study, especially when considering the
      low removal achieved by traditional activated sludge treatments, and the
      generation of carcinogenic trihalomethanes as a consequence of the chlorine
      oxidation methods frequently used in drinking water plants. [13] Fe0/H2O2
      systems, photodegradation using doped TiO2, and the use of dielectric barrier
      discharge reactors, seem to be the most promising techniques for the removal of
      3,4-DCA from water.

PMID- 29173039
TI  - Engineered aglycosylated full-length IgG Fc variants exhibiting improved
      FcgammaRIIIa binding and tumor cell clearance.
AB  - FcgammaRIIIa, which is predominantly expressed on the surface of natural killer
      cells, plays a key role in antibody-dependent cell-mediated cytotoxicity (ADCC),
      a major effector function of therapeutic IgG antibodies that results in the death
      of aberrant cells. Despite the potential uses of aglycosylated IgG antibodies,
      which can be easily produced in bacteria and do not have complicated glycan
      heterogeneity issues, they show negligible binding to FcgammaRIIIa and abolish
      the activation of immune leukocytes for tumor cell clearance, in sharp contrast
      to most glycosylated IgG antibodies used in the clinical setting. For directed
      evolution of aglycosylated Fc variants that bind to FcgammaRIIIa and, in turn,
      exert potent ADCC effector function, we randomized the aglycosylated Fc region of
      full-length IgG expressed on the inner membrane of Escherichia coli. Multiple
      rounds of high-throughput screening using flow cytometry facilitated the
      isolation of aglycosylated IgG Fc variants that exhibited higher binding affinity
      to FcgammaRIIIa-158V and FcgammaRIIIa-158F compared with clinical-grade
      trastuzumab (Herceptin(r)). The resulting aglycosylated trastuzumab IgG antibody
      Fc variants could elicit strong peripheral blood mononuclear cell-mediated ADCC
      without glycosylation in the Fc region.

PMID- 29173041
TI  - "The deceased has left; the alive has to move on": Experiences of Chinese Widows
      in the UK.
AB  - Relatively little is known about the experiences of Chinese widows, especially
      those living outside China. This qualitative study examines the experiences of
      eight Chinese or Hong Kong-born widows living in the UK. Using a semistructured
      approach to interviewing, participants were asked about their lives before,
      during, and after their spousal bereavement. Five major themes emerged: (1)
      complexity of marital lives; (2) experiences around the time of the death
      including fate; (3) loneliness and isolation; (4) the challenges of practical
      tasks; and finally, (5) current life. The implications of the findings for social
      policy and practice are briefly discussed.

PMID- 29173042
TI  - Antithrombin conformational modulation by D-myo-inositol 3,4,5,6
      tetrakisphosphate (TMI), a novel scaffold for the development of antithrombotic
      agents.
AB  - Antithrombin (AT) is a serpin that inhibits mainly thrombin and fXa after being
      activated by binding to glycosaminoglycans as heparin and heparan sulfate. Upon
      binding, the native AT conformation, relatively inactive as a protease inhibitor,
      is converted to an activated form. Recently, a new compound, named TMI, was
      discovered in our group with nanomolar affinity to antithrombin, and shown to be
      able to induce a partial activation of antithrombin. As TMI represents an
      original scaffold for structural optimizations aiming the development of new
      antithrombotic drugs, the present work demonstrated, through a series of
      molecular dynamics simulations, that TMI is able to modulate AT reactive center
      loop flexibility similarly to what is observed to heparin, as well as exposing AT
      P1 residue, Arg393. These results represent the first atomic level indication of
      AT conformational activation by TMI, and may offer a predictive basis for future
      studies aiming TMI structural optimization.

PMID- 29173043
TI  - Joint kinetic determinants of starting block performance in athletic sprinting.
AB  - The aim of this study was to explore the relationships between lower limb joint
      kinetics, external force production and starting block performance (normalised
      average horizontal power, NAHP). Seventeen male sprinters (100 m PB, 10.67 +/-
      0.32 s) performed maximal block starts from instrumented starting blocks (1000
      Hz) whilst 3D kinematics (250 Hz) were also recorded during the block phase.
      Ankle, knee and hip resultant joint moment and power were calculated at the rear
      and front leg using inverse dynamics. Average horizontal force applied to the
      front (r = 0.46) and rear (r = 0.44) block explained 86% of the variance in NAHP.
      At the joint level, many "very likely" to "almost certain" relationships (r =
      0.57 to 0.83) were found between joint kinetic data and the magnitude of
      horizontal force applied to each block although stepwise multiple regression
      revealed that 55% of the variance in NAHP was accounted for by rear ankle moment,
      front hip moment and front knee power. The current study provides novel insight
      into starting block performance and the relationships between lower limb joint
      kinetic and external kinetic data that can help inform physical and technical
      training practices for this skill.

PMID- 29173044
TI  - Spirituality/religiosity's influence on college students' adjustment to
      bereavement: A systematic review.
AB  - Bereavement is prevalent among college students and spirituality/religiosity may
      play an important role in their bereavement adjustment. This is the first
      systematic review to investigate the spirituality/religiosity's relationship with
      bereavement among college students. We searched 10 databases and screened 598
      studies. Eight studies met the inclusion criteria. Findings suggested a favorable
      association of spirituality/religiosity with desirable bereavement adjustment
      outcomes (growth, spiritual wellbeing, and psychological wellbeing), but mixed
      association with undesirable bereavement outcomes (distress). We provided
      directions for future research to further investigate the complex relationship
      between spirituality/religiosity and bereavement and to refine the meaning-making
      coping model for the college student population.

PMID- 29173045
TI  - Multiplicity issues in exploratory subgroup analysis.
AB  - The general topic of subgroup identification has attracted much attention in the
      clinical trial literature due to its important role in the development of
      tailored therapies and personalized medicine. Subgroup search methods are
      commonly used in late-phase clinical trials to identify subsets of the trial
      population with certain desirable characteristics. Post-hoc or exploratory
      subgroup exploration has been criticized for being extremely unreliable.
      Principled approaches to exploratory subgroup analysis based on recent advances
      in machine learning and data mining have been developed to address this
      criticism. These approaches emphasize fundamental statistical principles,
      including the importance of performing multiplicity adjustments to account for
      selection bias inherent in subgroup search. This article provides a detailed
      review of multiplicity issues arising in exploratory subgroup analysis.
      Multiplicity corrections in the context of principled subgroup search will be
      illustrated using the family of SIDES (subgroup identification based on
      differential effect search) methods. A case study based on a Phase III oncology
      trial will be presented to discuss the details of subgroup search algorithms with
      resampling-based multiplicity adjustment procedures.

PMID- 29173046
TI  - Harm caused by gambling among non-problem gamblers: Is a whole-of-population
      approach undervalued?

PMID- 29173047
TI  - Epidemiological, clinical and laboratory profile of scrub typhus cases detected
      by serology and RT-PCR in Kumaon, Uttarakhand: a hospital-based study.
AB  - We analysed the epidemiology, clinical and laboratory data of the 168 scrub
      typhus cases confirmed by a combination of any one of the following: real time
      polymerase chain reaction (RT-PCR) and/or immunofluorescence assay (IFA) (IgM
      and/or IgG). The peak season for scrub typhus was from July to October. By
      multivariate binary logistic regression analysis, the risk of scrub typhus was
      about four times in those working in occupation related to forest work. Major
      clinical manifestations were fever (100%), myalgia (65%), cough (51%) and
      vomiting (46%); major complications were meningitis/meningoencephatilitis (12.5%)
      and multi-organ failure (MOF) and pneumonia (5.3% each). Laboratory
      investigations revealed raised aminotranferase levels and thrombocytopenia in
      most confirmed cases. We conclude that scrub typhus is an important cause of
      febrile illness in the Kumaon hills of Uttarakhand where this disease had not
      previously been considered to exist.

PMID- 29173048
TI  - Nonspecific Symbiosis Between Sophora flavescens and Different Rhizobia.
AB  - We explored the genetic basis of the promiscuous symbiosis of Sophora flavescens
      with diverse rhizobia. To determine the impact of Nod factors (NFs) on the
      symbiosis of S. flavescens, nodulation-related gene mutants of representative
      rhizobial strains were generated. Strains with mutations in common nodulation
      genes (nodC, nodM, and nodE) failed to nodulate S. flavescens, indicating that
      the promiscuous nodulation of this plant is strictly dependent on the basic NF
      structure. Mutations of the NF decoration genes nodH, nodS, nodZ, and noeI did
      not affect the nodulation of S. flavescens, but these mutations affected the
      nitrogen-fixation efficiency of nodules. Wild-type Bradyrhizobium diazoefficiens
      USDA110 cannot nodulate S. flavescens, but we obtained 14 Tn5 mutants of B.
      diazoefficiens that nodulated S. flavescens. This suggested that the mutations
      had disrupted a negative regulator that prevents nodulation of S. flavescens,
      leading to nonspecific nodulation. For Ensifer fredii CCBAU 45436 mutants, the
      minimal NF structure was sufficient for nodulation of soybean and S. flavescens.
      In summary, the mechanism of promiscuous symbiosis of S. flavescens with rhizobia
      might be related to its nonspecific recognition of NF structures, and the host
      specificity of rhizobia may also be controlled by currently unknown nodulation
      related genes.

PMID- 29173049
TI  - Light directed migration of a cluster of cells in the centimeter scale.
AB  - Protein-based systems for light directed migration of cells have been
      demonstrated up to distances of several hundred microns, but larger distances in
      the centimeter scale would allow new possible applications. Light activated
      migration in mammalian cells can be achieved by cells expressing channelrhodopsin
      2 and an engineered Ca2+ sensitive Rac1 protein called RACer. In this study,
      light was used to induce wound healing, localize cells into a region of interest,
      and move cells over centimeter scale distances. Given the spatially complex
      organization of different types of cells in real tissue, light directed migration
      over the centimeter scale could potentially organize cell type arrangement to
      help develop more realistic tissues for transplantation.

PMID- 29173051
TI  - Suicide rates and information seeking via search engines: A cross-national
      correlational approach.
AB  - The volume of Google searches for suicide-related terms is positively associated
      with suicide rates, but previous studies used data from specific, restricted
      geographical contexts, thus, limiting the generalizability of this finding. We
      investigated the correlation between suicide-related search volume and suicide
      rates of 50 nations from five continents. We found a positive correlation between
      suicide rates and search volume, even after controlling for the level of
      industrialization. Results give credence to the global existence of a
      correlation. However, the reason why suicide-related search volume is higher in
      countries with higher suicide rates is still unclear and up to future research.

PMID- 29173050
TI  - Measles vaccination: Threat from related veterinary viruses and need for
      continued vaccination post measles eradication.
AB  - Measles virus (MV) is the only human virus within the morbillivirus genus of the
      Paramyxoviridae. The veterinary members are canine distemper virus (CDV), peste
      des petits ruminants virus (PPRV), Rinderpest Virus (RPV) as well as the marine
      morbilliviruses phocine distemper virus (PDV), dolphin morbillivirus (DMV) and
      porpoise morbillivirus (PMV). Morbilliviruses have a severe impact on humans and
      animal species. They confer diseases which have contributed to morbidity and
      mortality of the population on a global scale. There is substantial evidence from
      both natural and experimental infections that morbilliviruses can readily cross
      species barriers. Of most concern with regard to zoonosis is the more recently
      reported fatal infection of primates in Japan and China with strains of CDV which
      have adapted to this host. The close genetic relationship, shared cell entry
      receptors and similar pathogenesis between the morbilliviruses highlights the
      potential consequences of complete withdrawal of MV vaccination after
      eradication. Therefore, it would be prudent to continue the current MV
      vaccination. Ultimately development of novel, safe vaccines which have higher
      efficacy against the veterinary morbilliviruses is a priority. These would to
      protect the human population long term against the threat of zoonosis by these
      veterinary viruses.

PMID- 29173052
TI  - Abstracts from the October 2017 Pediatric Work Physiology Meeting.

PMID- 29173053
TI  - Alfred Walter Campbell's return to Australia.
AB  - Alfred Walter Campbell (1868-1937) established the basic cytoarchitectonic
      structure of the human brain while he was working as a pathologist at the
      Rainhill Lunatic Asylum near Liverpool in the United Kingdom. He returned to
      Australia in 1905 and continued doing research while establishing a neurological
      practice. His research over the next 17 years focused on four topics: (a)
      localisation in the cerebellum, (b) the neuroses and psychoses in war, (c)
      localisation in the cerebral cortex of the gorilla, and (d) the causes and
      pathology of the mysterious Australian "X" Disease (later known as Murray Valley
      encephalitis). In this article, I elaborate on his research in these areas, which
      provided evidence (a) against Louis Bolk's thesis that variation in the size of
      the cerebellar cortex reflected variation in the amount of cortex controlling
      various groups of muscle, (b) against the view that the neuroses and psychoses in
      war were different from those in civilian life, (c) for a parcelation of the
      cortex of the gorilla brain that supported his earlier findings in the higher
      apes, and (d) on the cause and pathophysiology of Australian "X" disease. Much of
      this research was overlooked, but it remains of considerable value and historical
      significance.

PMID- 29173054
TI  - A Global Declaration on Appropriate Use of Antimicrobial Agents across the
      Surgical Pathway.
AB  - This declaration, signed by an interdisciplinary task force of 234 experts from
      83 different countries with different backgrounds, highlights the threat posed by
      antimicrobial resistance and the need for appropriate use of antibiotic agents
      and antifungal agents in hospitals worldwide especially focusing on surgical
      infections. As such, it is our intent to raise awareness among healthcare workers
      and improve antimicrobial prescribing. To facilitate its dissemination, the
      declaration was translated in different languages.

PMID- 29173055
TI  - An Aristotelian view of therapists' practice in multifamily therapy for young
      adults with severe eating disorders.
AB  - BACKGROUND: Eating disorders are serious conditions which also impact the
      families of adult patients. There are few qualitative studies of multifamily
      therapy with adults with severe eating disorders and none concerning the practice
      of therapists in multifamily therapy. OBJECTIVES: The aim of the study is to
      explore therapists' practice in multifamily therapy. Research design and
      participants: A grounded theory approach was chosen. Data were collected through
      participant observation in two multifamily therapy groups and qualitative
      interviews with the therapists in those groups. Ethical considerations: The study
      conforms to the principles outlined in the Declaration of Helsinki. All
      participants in the multifamily therapy groups received information about the
      research project and signed consent forms. The data are treated confidentially
      and anonymised. FINDINGS: The core category was identified as 'having many
      strings to one's bow', consisting of three subcategories: 'planning and
      readjusting', 'developing as therapist and team' and 'regulating the temperature
      of the group'. This article discusses the empirical findings in the frame of
      Aristotelian virtue ethics.

PMID- 29173056
TI  - Enhancing the professional dignity of midwives: A phenomenological study.
AB  - BACKGROUND: When midwives are not treated with respect and their professional
      competencies are not recognised, their professional dignity is violated.
      OBJECTIVE: This study explored and described how the professional dignity of
      midwives in the selected hospital can be enhanced based on their experiences.
      RESEARCH DESIGN: A descriptive phenomenological research design was used with in
      depth interviews conducted with 15 purposely selected midwives. Ethical
      considerations: The Faculty of Health Sciences Research Ethics Committee of the
      University of Pretoria approved the study. The research was conducted in an
      academic tertiary hospital with voluntary participants. FINDINGS: To dignify
      midwives it is essential to enhance the following: 'to acknowledge the
      capabilities of midwives', 'to appreciate interventions of midwives', 'to
      perceive midwives as equal health team members', 'to invest in midwives', 'to
      enhance collegiality', 'to be cared for by management' and 'to create conducive
      environments'. CONCLUSION: The professional dignity of midwives is determined by
      their own perspectives of the contribution that they make to the optimal care of
      patients, the respect that they get from others and the support that hospital
      management gives them. With support and care, midwives' professional dignity is
      enhanced. Midwives will strive to render excellent services as well as increasing
      their commitment.

PMID- 29173057
TI  - Microbial composition of biofilm treating wastewater rich in bisphenol A.
AB  - Although microbial degradation plays a major role in the removal of bisphenol A
      (BPA) from water environments, there is little information on the effect of BPA
      on microorganisms in wastewater treatment systems. The aim of this study was to
      determine the dynamics of the microbial communities in biofilm growing on porous
      ceramic supports in a column up-flow reactor during exposure to BPA at increasing
      concentrations from 0 to 10 mg L-1. Independent of BPA load, the efficiency of
      BPA removal was about 90%. Groups of microorganisms that differ in their
      sensitivity to the presence of BPA in wastewater were identified. The core
      microbial genera in the biofilm were Acidovorax, Pseudoxanthomonas and
      Acinetobacter. Arenimonas sp., Thauera sp. and Acidobacterium sp. were the main
      components of the biofilm in the absence of BPA in wastewater. Increased
      abundances of Pseudomonas sp., Acidovorax sp. and Luteimonas sp. in BPA-exposed
      biofilm indicate that these genera may have played important roles in BPA
      biodegradation. A correlation between Pseudomonas sp. abundance and BPA removal
      efficiency indicates that BPA was used directly as a source of carbon and energy
      for growth. This study indicates that the use of the biofilm reactor enables
      effective BPA removal from wastewater and expands knowledge about the microbial
      structure of communities responsible for BPA degradation.

PMID- 29173058
TI  - Examining youth and caregiver reports of depression and anxiety in families
      seeking eating disorder treatment.
AB  - This study examines discrepancies between adolescent and caregiver reports of
      youth internalizing symptoms in families presenting for an initial eating
      disorder assessment. Initial diagnostic assessments of 49 adolescent-caregiver
      dyads seeking treatment at an urban pediatric hospital eating disorder clinic
      were utilized to examine differences between youth and caregiver reports of youth
      anxiety and depression symptoms. Caregivers reported significantly higher scores
      of major depression and generalized anxiety than adolescents (p=.000). Caregivers
      of youth with more severe ED symptoms exhibited more congruence with youth's own
      reports of their depression and anxiety. Our results suggest that agreement
      within families regarding comorbid psychological concerns may be beneficial in
      promoting treatment uptake for those who desire a reduction in depression and
      anxiety symptoms, regardless of motivation to change eating behaviors.

PMID- 29173060
TI  - Author's Reply: TK2-related Myopathic Mitochondrial Depletion Syndrome.

PMID- 29173059
TI  - Mannosylated thiolated polyethylenimine nanoparticles for the enhanced efficacy
      of antimonial drug against Leishmaniasis.
AB  - AIM: Our aim was to inhibit trypanothione reductase (TR) and P-gp efflux pump of
      Leishmania by the use of thiolated polymers. Thus, increasing the intracellular
      accumulation and therapeutic effectiveness of antimonial compounds. METHODS:
      Mannosylated thiolated chitosan and mannosylated thiolated chitosan
      polyethyleneimine graft were synthesized and characterized. Meglumine antimoniate
      loaded nanoparticles were prepared and evaluated for TR and P-gp efflux pump
      inhibition, biocompatibility, macrophage uptake and antileishmanial potential.
      RESULTS: Thiomers inhibited TR with Ki 2.021. The macrophage uptake was 33.7- and
      18.9-fold higher with mannosylated thiolated chitosan-polyethyleneimine graft and
      mannosylated thiolated chitosan nanoparticles, respectively, as compared with the
      glucantime. Moreover, the in vitro antileishmanial activity showed 14.41- and 7.4
      fold improved IC50 for M-TCS-g-PEI and M-TCS, respectively as compared with
      glucantime. CONCLUSION: These results encouraged the concept that TR and P-gp
      inhibition by the use of thiomers improves the therapeutic efficacy of antimonial
      drugs.

PMID- 29173061
TI  - Targeted Sequencing of Malignant Supratentorial Pediatric Brain Tumors
      Demonstrates a High Frequency of Clinically Relevant Mutations.
AB  - Pediatric brain tumors cause more deaths than any other childhood malignancy, and
      the identification of potentially actionable genomic alterations in this rare
      heterogeneous group of tumors may improve treatment and outcome. The genetic
      landscape of common posterior fossa tumors has been described in the past several
      years, yet the classification of malignant pediatric supratentorial tumors
      remains controversial. Next-generation sequencing (NGS) is a promising tool to
      evaluate multiple genes concurrently. The clinical utility of NGS has not been
      proven in pediatric brain tumors. We identified patients diagnosed with high
      grade supratentorial pediatric brain tumors resected between 2008 and 2012 at our
      institution. DNA from 12 formalin-fixed paraffin-embedded tumor samples from 9
      patients was analyzed, including 3 paired samples from diagnosis and relapse. A
      panel of 194 cancer-related genes was sequenced using targeted next-generation
      deep sequencing. Genetic findings were correlated with histology,
      immunohistochemistry, treatment, and survival. We found one or more pathologic
      genetic change (mutation, amplification, or deletion) in 8 of 9 (89%) of patients
      studied. Epidermal Growth Factor Receptor ( EGFR) mutations were found in 3
      patients, 2 of which had an exon 20 insertion not previously described in
      pediatric malignancy. Additional genetic changes were found in EGFR and Platelet
      Derived Growth Factor Receptor Alpha ( PDGFRA) at relapse not present in the
      initial samples. Familial cancer predisposition syndromes were suggested by
      mutations found in 3 genes in 4 patients, including TP53, MSH2, and CHEK2. Seven
      of 9 patients in this study died of their disease. In summary, targeted deep
      sequencing may be used in rare pediatric brain tumors to identify driver
      mutations for targeted therapy, suggest constitutional and familial testing for
      cancer predisposition syndromes, and select molecular targets worthy of further
      study.

PMID- 29173062
TI  - TK2-related Myopathic Mitochondrial Depletion Syndrome.

PMID- 29173063
TI  - Development of a pre-glycoengineered CHO-K1 host cell line for the expression of
      antibodies with enhanced Fc mediated effector function.
AB  - Novel biotherapeutic glycoproteins, like recombinant monoclonal antibodies (mAbs)
      are widely used for the treatment of numerous diseases. The N-glycans attached to
      the constant region of an antibody have been demonstrated to be crucial for the
      biological efficacy. Even minor modifications of the N-glycan structure can
      dictate the potency of IgG effector functions such as the antibody-dependent cell
      mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Here,
      we present the development of a glycoengineered CHO-K1 host cell line (HCL),
      stably expressing beta1,4-N-Acetylglucoseaminyltransferase III (GnT-III) and
      alpha-mannosidase II (Man-II), for the expression of a-fucosylated antibodies
      with enhanced Fc-mediated effector function. Glycoengineered HCLs were generated
      in a two-step strategy, starting with generating parental HCLs by stable
      transfection of CHO-K1 cells with GnT-III and Man-II. In a second step, parental
      HCLs were stably transfected a second time with these two transgenes to increase
      their copy number in the genetic background. Generated glycoengineered CHO-K1
      cell lines expressing two different mAbs deliver antibody products with a content
      of more than 60% a-fucosylated glycans. In-depth analysis of the N-glycan
      structure revealed that the majority of the Fc-attached glycans of the obtained
      mAbs were of complex bisected type. Furthermore, we showed the efficient use of
      FcgammaRIIIa affinity chromatography as a novel method for the fast assessment of
      the mAbs a-fucosylation level. By testing different cultivation conditions for
      the pre-glycoengineered recombinant CHO-K1 clones, we identified key components
      essential for the production of a-fucosylated mAbs. The prevalent effect could be
      attributed to the trace element manganese, which leads to a strong increase of a
      fucosylated complex- and hybrid-type glycans. In conclusion, the novel pre
      glycoengineered CHO-K1 HCL can be used for the production of antibodies with high
      ratios of a-fucosylated Fc-attached N-glycans. Application of our newly developed
      FcgammaRIIIa affinity chromatography method during cell line development and use
      of optimized cultivation conditions can ultimately support the efficient
      development of a-fucosylated mAbs.

PMID- 29173064
TI  - Pharmacogenetics of drug-induced ototoxicity caused by aminoglycosides and
      cisplatin.
AB  - Aminoglycosides and the anticancer drug cisplatin can cause permanent hearing
      loss, which impacts patients' quality of life and results in considerable
      subsequent costs. Since patients' individual susceptibility to aminoglycoside-
      and cisplatin-induced ototoxicity varies considerably, strategies are needed to
      identify patients at risk, who may require alternative treatments or specific
      protection strategies. For both drugs, various genetic variants were linked to an
      increased or decreased risk for ototoxicity. Except for the association between
      the A1555G mitochondrial DNA mutation and aminoglycoside ototoxicity, their
      evidence is considered low because study cohorts were often small and replication
      studies either missing or contradictory. This review summarizes the
      pharmacogenetic markers linked to aminoglycoside- or cisplatin-induced
      ototoxicity and discusses reasons for replication failure and future perspective.

PMID- 29173065
TI  - Neurobehavioural effects of Lactobacillus rhamnosus GG alone and in combination
      with prebiotics polydextrose and galactooligosaccharide in male rats exposed to
      early-life stress.
AB  - Early life is a period of significant brain development when the brain is at its
      most plastic and vulnerable. Stressful episodes during this window of development
      have long-lasting effects on the central nervous system. Rodent maternal
      separation (MS) is a reliable model of early-life stress and induces alterations
      in both physiology and behaviour. Intriguingly, the gut microbiota of MS
      offspring differ from that of non-separated offspring, suggesting a mechanistic
      role for the microbiota-gut-brain axis. Hence, we tested whether dietary factors
      known to affect the gut microbiota alter the neurobehavioural effects of MS. The
      impact of consuming diet containing prebiotics polydextrose (PDX) and
      galactooligosaccharide (GOS) alone or in combination with live bacteria
      Lactobacillus rhamnosus GG (LGG) from weaning onwards in rats subjected to early
      life MS was assessed. Adult offspring were assessed for anxiety-like behaviour in
      the open field test, spatial memory using the Morris water maze, and reactivity
      to restraint stress. Brains were examined via PCR for changes in mRNA gene
      expression. Here, we demonstrate that diets containing a combination of PDX/GOS
      and LGG attenuates the effects of early-life MS on anxiety-like behaviour and
      hippocampal-dependent learning with changes to hippocampal mRNA expression of
      genes related to stress circuitry, anxiety and learning.

PMID- 29173066
TI  - Expression of genes related to antioxidant activity in Nile tilapia kept under
      salinity stress and fed diets containing different levels of vitamin C.
AB  - The aim of this study was to examine whether (1) severe changes in salinity
      produced increased stress, and (2) vitamin C supplementation might reduce the
      observed damage in Nile tilapia. The parameters measured included condition
      factor, survival rate, and gene expression of catalase (CAT), heat shock protein
      70 (HSP70), glutathione reductase (GSR), glutathione synthase (GSS), and
      glutathione peroxidase (GPx). The investigation was conducted with 160 Nile
      tilapia divided into four treatment groups: freshwater; 7 or 21 parts per
      thousand (0/00) salinity, all fed a basal diet; as well as a fourth treatment
      group consisting of fish kept at 210/00 salinity fed a diet supplemented with
      vitamin C (1500 mg/kg). For gene expression analysis, liver samples were
      collected after 24 h or after 14 d. After 24 h, fish raised in 210/00 salinity
      and fed with the diet supplemented with vitamin C showed similar GPx expression
      as the control freshwater group. GSS expression in 210/00 salinity was similar to
      fish exposed to 70/00 salinity. Nile tilapia exposed to 210/00 salinity without
      vitamin C supplementation exhibited the highest HSP70 gene expression levels
      after 24 h. After 14-dtreatment, the lowest survival rate was observed in the
      210/00 salinity group. After 14 d, the highest expression of GPx and GSR levels
      was detected in fish in the 210/00 salinity group that received vitamin C. Data
      indicate that vitamin C supplementation enhanced the expression of genes related
      to antioxidant capacity in Nile tilapia exposed to higher salinity, thereby
      increasing protection against the oxidative effects induced by high water
      salinity.</AB>.

PMID- 29173067
TI  - WhatsApp: An Innovative Tool for Dermatology Care in Limited Resource Settings.

PMID- 29173068
TI  - Development and application of oxidative stress biomarkers.
AB  - Oxidative stress may cause a wide variety of free radical reactions to produce
      deleterious modifications in membranes, proteins, enzymes, and DNA. Reactive
      Oxygen Species (ROS) generated by myeloperoxidase (MPO) can induce lipid
      peroxidation and also play an important role in the generation of reactive
      chlorinating and brominating species. As the universal biomarkers, chemical, and
      immunochemical approach on oxidatively modified and halogenated tyrosines has
      been carried out. As amido-type adduct biomarkers, chemical, and immunochemical
      evaluation of hexanoyl- and propanoyl-lysines, hexanoyl- and propanoyl-dopamines
      and phospholipids were prepared and developed for application of evaluation of
      novel antioxidative functional food factors. We have also involved in application
      of oxidatively modified DNAs such as 8-hydroxy- and 8-halogenated deoxyguanosines
      as the useful biomarkers for age-related diseases using both in vitro and in vivo
      systems. Application of these oxidative stress biomarkers for novel type of
      functional food development and recent approach for development of novel
      evaluation systems are also discussed.

PMID- 29173069
TI  - Direct Detection of Vibrio vulnificus, Vibrio parahaemolyticus, and Vibrio
      alginolyticus from Clinical and Environmental Samples by a Multiplex Touchdown
      Polymerase Chain Reaction Assay.
AB  - BACKGROUND: Vibrio vulnificus, V. alginolyticus, and V. parahaemolyticus are
      commonly and opportunistically pathogenic to humans. METHODS: In this study, a
      novel multiple touchdown polymerase chain reaction method (MT-PCR) was developed
      to benefit rapid and simultaneous detection of the presence of the three Vibrio
      species from the enriched clinical and environmental samples. RESULTS: The method
      showed a sensitivity of 104 colony forming units (CFU)/mL for V. vulnificus, 103
      CFU/mL for V. parahaemolyticus and V. alginolyticus, and a specificity of 100%
      for all the three Vibrio species. All strains of the three Vibrio species were
      detected in the spiked samples artificially contaminated with reference strains
      and were identified directly from the enriched clinical and environmental samples
      within three hours by this MT-PCR assay. All the corresponding bacteria were
      isolated from these enriched samples in 48 hours by standard microbiologic
      procedures. CONCLUSIONS: This MT-PCR method, which can detect V. vulnificus, V.
      parahaemolyticus, and V. alginolyticus directly and simultaneously, was rapid,
      sensitive, specific, and can be used in clinical diagnostics, food industry
      studies, and risk assessment of environment.

PMID- 29173070
TI  - Generalist versus Subspecialist Characteristics of the U.S. Radiologist
      Workforce.
AB  - Purpose To assess subspecialty practice characteristics of the U.S. radiologist
      workforce. Materials and Methods This study used the Medicare Physician and Other
      Supplier Public Use File and did not constitute human subject research. The
      authors identified 33 090 radiologists who billed for professional services
      between 2012 and 2014 and used a validated classification system to map services
      to seven subspecialties and quantify subspecialty-focused effort on the basis of
      work relative value units (RVUs). Radiologists with more than half of their
      billed work RVUs in a single subspecialty were designated subspecialists; the
      remainder were classified as generalists. Matching radiologists with various
      characteristics extracted from other publicly available data sets, associations
      were explored through use of analysis of variance and multivariable logistic
      regression. Results More than half (55.3%) of U.S. radiologists practice
      predominantly as generalists but dedicate on average 36.0% effort to one
      subspecialty. Among radiologists practicing as majority subspecialists,
      neuroradiologists (10.1% of all radiologists) and breast imagers (8.4%) are most
      common. Subspecialization is more common (P < .001) among radiologists who are
      female, are earlier in their career, work in larger practices, have academic
      affiliations, and practice in the Northeast. By subspecialty, female
      representation varies from 8.6% (interventional radiology) to 63.1% (breast
      imaging); cardiothoracic imagers were more commonly early career radiologists,
      and nuclear medicine physicians were later career radiologists. Subspecialization
      is considerably more common in larger (>=100 members) practices (63.1%). An
      academic affiliation is the strongest independent predictor of subspecialization
      (odds ratio, 3.56; 95% confidence interval: 3.30, 3.84). Conclusion Despite an
      increased focus on radiology subspecialization, most U.S. radiologists are
      majority general radiologists on the basis of their work RVUs. Subspecialization
      is by far more prevalent in larger and academic practices. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 29173071
TI  - Systematic Review and Meta-Analysis of CT Features for Differentiating
      Complicated and Uncomplicated Appendicitis.
AB  - Purpose To perform a systematic review and meta-analysis to identify computed
      tomographic (CT) features for differentiating complicated appendicitis in
      patients suspected of having appendicitis and to summarize their diagnostic
      accuracy. Materials and Methods Studies on diagnostic accuracy of CT features for
      differentiating complicated appendicitis (perforated or gangrenous appendicitis)
      in patients suspected of having appendicitis were searched in Ovid-MEDLINE,
      EMBASE, and the Cochrane Library. Overlapping descriptors used in different
      studies to denote the same image finding were subsumed under a single CT feature.
      Pooled diagnostic accuracy of the CT features was calculated by using a bivariate
      random effects model. CT features with pooled diagnostic odds ratios with 95%
      confidence intervals not including 1 were considered as informative. Results
      Twenty-three studies were included, and 184 overlapping descriptors for various
      CT findings were subsumed under 14 features. Of these, 10 features were
      informative for complicated appendicitis. There was a general tendency for these
      features to show relatively high specificity but low sensitivity. Extraluminal
      appendicolith, abscess, appendiceal wall enhancement defect, extraluminal air,
      ileus, periappendiceal fluid collection, ascites, intraluminal air, and
      intraluminal appendicolith showed pooled specificity greater than 70% (range, 74%
      100%), but sensitivity was limited (range, 14%-59%). Periappendiceal fat
      stranding was the only feature that showed high sensitivity (94%; 95% confidence
      interval: 86%, 98%) but low specificity (40%; 95% confidence interval, 23%, 60%).
      Conclusion Ten informative CT features for differentiating complicated
      appendicitis were identified in this study, nine of which showed high
      specificity, but low sensitivity. (c) RSNA, 2017 Online supplemental material is
      available for this article.

PMID- 29173072
TI  - "Social Networkout": Connecting Social Features of Wearable Fitness Trackers with
      Physical Exercise.
AB  - Despite widespread understanding of the benefits of physical activity, many
      adults in the United States do not meet recommended exercise guidelines.
      Burgeoning technologies, including wearable fitness trackers (e.g., Fitbit, Apple
      watch), bring new opportunities to influence physical activity by encouraging
      users to track and share physical activity data and compete against their peers.
      However, research has not explored the social processes that mediate the
      relationship between the use of wearable fitness trackers and intention to
      exercise. In this study, we applied the Theory of Planned Behavior (Ajzen, 1991)
      to explore the effects of two communicative features of wearable fitness devices
      social sharing and social competing-on individuals' intention to exercise.
      Drawing upon surveys from 238 wearable fitness tracker users, we found that the
      relationship between the two communication features (social sharing and
      competing) and exercise intention was mediated by attitudes, subjective norms,
      and perceived behavioral control. The results suggest that the ways in which
      exercise data are shared significantly influence the exercise intentions, and
      these intentions are mediated by individuals' evaluation of exercise, belief
      about important others' approval of exercise, and perceived control upon
      exercise.

PMID- 29173073
TI  - In vivo assessment of plant extracts for control of plant diseases: A
      sesquiterpene ketolactone isolated from Curcuma zedoaria suppresses wheat leaf
      rust.
AB  - As an alternative to synthetic pesticides, natural materials such as plant
      extracts and microbes have been considered to control plant diseases. In this
      study, methanol extracts of 120 plants were explored for in vivo antifungal
      activity against Rhizoctonia solani, Botrytis cinerea, Phytophthora infestans,
      Puccinia triticina, and Blumeria graminis f. sp. hordei. Of the 120 plant
      extracts, eight plant extracts exhibited a disease control efficacy of more than
      90% against at least one of five plant diseases. In particular, a methanol
      extract of Curcuma zedoaria rhizomes exhibited strong activity against wheat leaf
      rust caused by P. triticina. When the C. zedoaria methanol extracts were
      partitioned with various solvents, the layers of n-hexane, methylene chloride,
      and ethyl acetate showed disease control values of 100, 80, and 43%,
      respectively, against wheat leaf rust. From the C. zedoaria rhizome extracts, an
      antifungal substance was isolated and identified as a sesquiterpene ketolactone
      based on the mass and nuclear magnetic resonance spectral data. The active
      compound controlled the development of rice sheath blight, wheat leaf rust, and
      tomato late blight. Considering the in vivo antifungal activities of the
      sesquiterpene ketolactone and the C. zedoaria extracts, these results suggest
      that C. zedoaria can be used as a potent fungicide in organic agriculture.

PMID- 29173074
TI  - Improving the power to establish clinical similarity in a Phase 3 efficacy trial
      by incorporating prior evidence of analytical and pharmacokinetic similarity.
AB  - To improve patients' access to safe and effective biological medicines,
      abbreviated licensure pathways for biosimilar and interchangeable biological
      products have been established in the US, Europe, and other countries around the
      world. The US Food and Drug Administration and European Medicines Agency have
      published various guidance documents on the development and approval of
      biosimilars, which recommend a "totality-of-the-evidence" approach with a
      stepwise process to demonstrate biosimilarity. The approach relies on
      comprehensive comparability studies ranging from analytical and nonclinical
      studies to clinical pharmacokinetic/pharmacodynamic (PK/PD) and efficacy studies.
      A clinical efficacy study may be necessary to address residual uncertainty about
      the biosimilarity of the proposed product to the reference product and support a
      demonstration that there are no clinically meaningful differences. In this
      article, we propose a statistical strategy that takes into account the similarity
      evidence from analytical assessments and PK studies in the design and analysis of
      the clinical efficacy study in order to address residual uncertainty and enhance
      statistical power and precision. We assume that if the proposed biosimilar
      product and the reference product are shown to be highly similar with respect to
      the analytical and PK parameters, then they should also be similar with respect
      to the efficacy parameters. We show that the proposed methods provide correct
      control of the type I error and improve the power and precision of the efficacy
      study upon the standard analysis that disregards the prior evidence. We confirm
      and illustrate the theoretical results through simulation studies based on the
      biosimilars development experience of many different products.

PMID- 29173075
TI  - Evaluation of Plasma Growth Factors (VEGF, PDGF, EGF, ANG1, and ANG2) in Patients
      with Varicose Veins Before and After Treatment with Endovenous Laser Ablation.
AB  - OBJECTIVE: To measure pre- and postoperative plasma concentrations of growth
      factors (VEGF, PDGF, EGF, ANG1, and ANG2) in patients with primary lower limb
      varicose veins (VVs) treated with endovenous laser ablation (EVLA). BACKGROUND:
      Many studies have explored the potential relationship between primary VVs and
      growth factors. No previous studies were done for patients treated with EVLA.
      MATERIALS AND METHODS: Blood samples were obtained from 30 patients with primary
      VVs undergoing treatment with EVLA before and 1 week after treatment. Similar
      samples were obtained from 20 healthy matched adults as a control. Plasma
      concentrations of growth factor derivatives (VEGF, PDGF, EGF, ANG1, and ANG2)
      were measured through commercially available enzyme-linked immunosorbent assay.
      RESULTS: There was statistically significant reduction in median plasma growth
      factor (VEGF, PDGF, EGF, and ANG1) levels in the preoperative group (p = 0.001)
      when compared with the control group except for ANG2, which showed increased
      plasma level (p = 0.001). However, values of plasma concentration of those growth
      factors after treatment with EVLA were nearly equal to the control group,
      especially in EGF and VEGF (p = 0.564, 0.515, respectively). CONCLUSIONS: The
      altered plasma concentrations of growth factors VEGF, PDGF, EGF, ANG1, and ANG2
      among patients with VVs normalized 1 week after treatment with EVLA compared with
      the control group. This may support the role of these factors in the pathogenesis
      of the disease. Future studies may evaluate if these changes can play a
      prognostic and/or predictive value regarding the adequacy of treatment and the
      possibility of recurrence.

PMID- 29173076
TI  - Non-occlusive mesenteric ischemia: two case reports and a short review of the
      literature.
AB  - INTRODUCTION: Non-occlusive mesenteric ischemia (NOMI) is an infrequent cause of
      acute mesenteric ischemia with atypical symptoms and a high mortality. PATIENTS
      AND METHODS: We report two cases of NOMI characterized by their difference in
      etiology, treatment and outcome. RESULTS: In the first case, the patient
      developed NOMI after septic shock, she was successfully treated with surgery. The
      second patient experienced two episodes of cardiac arrest followed by NOMI. He
      received only supportive care and died shortly after. We present a short review
      of the literature, discussing epidemiology, pathophysiology, clinical
      presentations, diagnosis and management of NOMI. CONCLUSION: NOMI is a rare
      disease with a difficult diagnosis. Early recognition and treatment with
      supportive therapy, vasodilator drugs and possibly surgery can significantly
      lower mortality.

PMID- 29173077
TI  - Family centred care in the paediatric high dependency unit: Parents' and Staff's
      perceptions.
AB  - AIM: This study explored parent and staff perceptions of family centred care
      (FCC) within a paediatric high dependency in one New Zealand hospital.
      BACKGROUND: FCC is a partnership approach to healthcare delivery where the
      child's treatment is aligned to the family's needs. Despite widespread
      endorsement of FCC, variations between parents and staff in healthcare settings
      continues to be evident. METHOD: A descriptive qualitative cross-sectional design
      was used with a convenience sample where written responses for one open ended
      question from 91 parents and 66 staff resident with their child or working within
      a paediatric high dependency unit in New Zealand. RESULTS: The parents' responses
      generated three themes (family, treatment and relationships) and the staff's
      responses generated two themes (family and treatment). CONCLUSION: Whilst there
      were similarities in describing the meaning of family centred care between
      parents and staff, their views on the central focus of this differed.

PMID- 29173078
TI  - OMICS, Oral Cancer Molecular Landscapes, and Clinical Practice.
AB  - Molecular pathogenesis of oral cancers continues to be researched by omics
      systems science biotechnologies. Oral cancers rank as the 13th most common cancer
      globally. Notably, the burden of oral cancers from the Asian continent is 56.21%,
      with 26% of the burden contributed by India. Despite easy accessibility of the
      oral cavity and hence early detection of oral cancers, majority are diagnosed in
      advanced stages in the Asian countries. Innovation in oral cancer diagnostics, as
      well as theranostics for precision medicine, would aid their early diagnosis,
      prognosis, and treatment, not to mention discovery of novel molecular targets for
      drug development. This expert review offers an analysis of oral cancer
      biomarkers, including somatic mutations, deregulated expression, epigenetic
      regulation, and genomic variants associated with oral cancer. We also discuss the
      implications of the current and emerging oral cancer biomarkers with a view to
      clinical practice, global health, and make suggestions for the ways forward.

PMID- 29173079
TI  - What influences intentions to request physician-assisted euthanasia or continuous
      deep sedation?
AB  - The increasing prevalence of euthanasia in Belgium has been linked to changing
      attitudes. Using National health survey data (N = 9651), we investigated Belgian
      adults' intention to ask a physician for euthanasia or continuous deep sedation
      in the hypothetical scenario of a terminal illness and examined its connection to
      sociodemographic and health characteristics. Respectively, 38.3 and 25.8% could
      envisage asking for euthanasia and continuous deep sedation. Those with very bad
      to fair subjective health and with depression more likely had an intention to ask
      for euthanasia, which suggests need for attention in the evaluation of requests
      from specific patient groups.

PMID- 29173080
TI  - Eating disorder mental health literacy: What do psychologists, naturopaths, and
      fitness instructors know?
AB  - At present, there are no known studies investigating the eating disorder mental
      health literacy (ED-MHL) of common frontline health providers such as
      psychologists, naturopaths, and fitness instructors. Little research also exists
      around practitioner knowledge for the spectrum of eating disorders. The current
      study sought to fill these research gaps and comprised 115 health practitioners
      who completed an online survey. A fictional vignette describing a female (Sarah)
      experiencing a subthreshold bulimic variant without purging was presented
      alongside common ED-MHL items. Almost 4 in 10 psychologists, 7 in 10 natural
      therapists, and 8 in 10 fitness instructors failed to detect a general eating
      disorder, with the latter two groups more likely to believe the problem was a
      self-esteem issue. Perceived helpfulness of people and interventions varied from
      best practice clinical guidelines, with physical/medical risk management not
      prioritized, pharmacotherapy viewed poorly, and doctors seen as one of the least
      helpful people. Although Sarah's problem was seen as severe and highly common
      (which may speak to the volume of undetected eating disorders), alarmingly 36.7%
      of fitness instructors viewed her predicament as desirable given weight lost.
      This novel study highlights the need for specific training interventions to
      improve health practitioners' ED-MHL, particularly around atypical eating
      disorder presentations, which may facilitate earlier detection and help-seeking
      for evidence-based interventions rather than expenditure on unhelpful or even
      harmful treatments, leading to improved community health and lives saved.

PMID- 29173082
TI  - Spirituality at End of Life: The Role of Hospice Social Work.

PMID- 29173083
TI  - Between butch/femme: On the performance of race, gender, and sexuality in a
      YouTube web series.
AB  - Drawing on a legacy of Black television and film production, Black web series
      remediate earlier media forms in order to usher in a twenty-first-century revival
      of indie Black cultural production. Specifically, video sharing and social media
      platforms operate as a sphere in which content creators and users are afforded
      unique opportunities to engage with video content and each other on a variety of
      levels. Focusing on the YouTube media sphere, one can also observe the myriad
      ways in which the performance of race, gender, and sexuality influences the types
      of discourse that circulate within these sites. In watching and analyzing Black
      queer web series on YouTube, I examine how the performance of gender and
      sexuality by Black queer women within and outside of web series are policed and
      protected by both community insiders and outsiders. Utilizing an ethnographic
      framework, which includes a critical discourse analysis of the YouTube comments
      for the series Between Women, as well as a textual analysis of series content,
      this project draws conclusions about the role that the politics of pleasure,
      performance, and the public sphere play in the recognition and/or refusal of
      queer sexuality within Black communities.

PMID- 29173081
TI  - Varicella Virus Vaccination in the United States.
AB  - Varicella zoster virus (VZV) is the cause of chickenpox (varicella) and shingles
      (zoster), and was once responsible for over 4 million infections in the United
      States annually. The development of a live attenuated VZV vaccine was initially
      viewed with extreme skepticism. Nonetheless, a VZV vaccine was developed in the
      1970s by Takahashi and his colleagues in Japan and was eventually licensed in the
      US. It is now known to be one of the safest and most effective vaccines available
      and is administered worldwide. Here are described important factors that
      contributed to the successful research and licensure of the highly successful VZV
      vaccine.

PMID- 29173085
TI  - Epigenetics-by-Sex Interaction for Coronary Artery Disease Risk Conferred by the
      Cystathionine gamma-Lyase Gene Promoter Methylation.
AB  - Coronary artery disease (CAD) is a major global health burden whereby gene-by
      environment-by-sex interactions play an important role. Coronary artery bypass
      graft (CABG) surgery involves patients with well-documented and severe CAD.
      Hence, the study of CAD in a context of the CABG surgery serves as an
      advantageous model for disease phenotype ascertainment and genetic association
      studies. We report here new observations from a case-control genetic association
      study on promoter methylation of the cystathionine gamma-lyase (CTH) gene and its
      association with CAD. To the best of our knowledge, this is the first clinical
      study to show the DNA methylation status of the CTH promoter in relation to this
      clinical phenotype. CTH encodes for the hydrogen sulfide generating enzyme named
      CSE in the endothelium that is mechanistically highly relevant for CAD. In a
      sample of 334 subjects from Greece (178 cases with CAD and who underwent CABG,
      and 156 controls), CTH promoter methylation was analyzed using a SYBR Green-based
      quantitative methylation-specific polymerase chain reaction. We found increased
      methylation in CTH promoter in cases (19.1%) compared to controls (10.3%) (p =
      0.024). Gene-by-sex analysis sustained the significant association in men (p =
      0.032) but not in women (p = 0.884). By using multivariate analyses after
      controlling for potential confounders such as smoking, age, and gender, we found
      that increased CTH gene promoter methylation was associated with CAD in the total
      sample (odds ratio [OR] = 2.163, 95% confidence interval [CI] 1.038-4.506, p =
      0.039) and in men (OR = 2.418, 95% CI 1.048-5.581, p = 0.039) but not in women
      (OR = 0.542, 95% CI 0.094-3.140, p = 0.495). These observations collectively
      warrant further precision medicine and biomarker research to examine the CTH
      methylation status as a putative epigenetic regulator of CAD risk in larger and
      independent samples.

PMID- 29173084
TI  - Multi-Drug-Resistant Gram-Negative Infections in Deployment-Related Trauma
      Patients.
AB  - BACKGROUND: The contribution of multi-drug-resistant gram-negative bacilli
      infections (MDRGN-I) in patients with trauma is not well described. We present
      characteristics of MDRGN-Is among military personnel with deployment-related
      trauma (2009-2014). PATIENTS AND METHODS: Data from the Trauma Infectious Disease
      Outcomes Study were assessed for infectious outcomes and microbial recovery.
      Infections were classified using standardized definitions. Gram-negative bacilli
      were defined as multi-drug-resistant if they showed resistance to >=3 antibiotic
      classes or were producers of extended-spectrum beta-lactamase or carbapenemases.
      RESULTS: Among 2,699 patients admitted to participating U.S. hospitals, 913
      (33.8%) experienced >=1 infection event, of which 245 (26.8%) had a MDRGN-I.
      There were 543 MDRGN-I events (24.6% of unique 2,210 infections) with Escherichia
      coli (48.3%), Acinetobacter spp. (38.6%), and Klebsiella pneumoniae (8.4%) as the
      most common MDRGN isolates. Incidence of MDRGN-I was 9.1% (95% confidence
      interval [CI]: 8.0-10.2). Median time to MDRGN-I event was seven days with 75%
      occurring within 13 days post-trauma. Patients with MDRGN-Is had a greater
      proportion of blast injuries (84.1% vs. 62.5%; p < 0.0001), traumatic amputations
      (57.5% vs. 16.3%; p < 0.0001), and higher injury severity (82.0% had injury
      severity score >=25 vs. 33.7%; p < 0.0001) compared with patients with either no
      infections or non-MDRGN-Is. Furthermore, MDRGN-I patients were more frequently
      admitted to the intensive care unit (90.5% vs. 48.5%; p < 0.0001), colonized with
      a MDRGN before infection (58.0% vs. 14.7%; p < 0.0001), and required mechanical
      ventilation (78.0% vs. 28.8% p < 0.0001). Antibiotic exposure before the MDRGN-I
      event was significantly higher across antibiotic classes except first generation
      cephalosporins and tetracyclines, which were very commonly used with all
      patients. Regarding outcomes, patients with MDRGN-Is had a longer length of
      hospitalization than the comparator group (53 vs. 18 days; p < 0.0001).
      CONCLUSIONS: We found a high rate of MDRGN-I in our population characterized by
      longer hospitalization and greater injury severity. These findings inform
      treatment and infection control decisions in the trauma patient population.

PMID- 29173086
TI  - Evaluation of ultrasonography guidance for single-puncture temporomandibular
      joint arthrocentesis: A randomized clinical study.
AB  - Objective To evaluate ultrasonography (US) guidance on the single-puncture
      temporomandibular joint (TMJ) arthrocentesis technique. Methods Twenty-four
      patients were randomly divided into two groups (n = 12 in each group), and single
      puncture arthrocentesis (SPA) was performed with and without US guidance in
      groups 1 and 2. During the one-year follow-up period, the groups were
      statistically evaluated by the visual analog scale for pain, maximum mouth
      opening, lateral excursion, and protrusion within each group and between the two
      groups. Results Both treatment groups showed significant improvement, compared to
      the baseline levels for almost all outcome variables. However, there were no
      statistically significant differences between groups 1 and 2 (p > 0.05).
      Conclusion US guidance can be used for cannula placement in SPA. However, the
      outcome results are the same with or without its use.

PMID- 29173087
TI  - Influence of process parameters on the effectiveness of photooxidative treatment
      of pharmaceuticals.
AB  - In this study, UV-C/H2O2 and UV-C/[Formula: see text] processes as photooxidative
      Advanced oxidation processes were applied for the treatment of seven
      pharmaceuticals, either already included in the Directive 2013/39/EU "watch list"
      (17alpha- ethynylestradiol, 17beta-estradiol) or with potential to be added in
      the near future due to environmental properties and increasing consumption
      (azithromycin, carbamazepine, dexamethasone, erythromycin and oxytetracycline).
      The influence of process parameters (pH, oxidant concentration and type) on the
      pharmaceuticals degradation was studied through employed response surface
      modelling approach. It was established that degradation obeys first-order kinetic
      regime regardless structural differences and over entire range of studied process
      parameters. The results revealed that the effectiveness of UV-C/H2O2 process is
      highly dependent on both initial pH and oxidant concentration. It was found that
      UV-C/[Formula: see text] process, exhibiting several times faster degradation of
      studied pharmaceuticals, is less sensitive to pH changes providing practical
      benefit to its utilization. The influence of water matrix on degradation kinetics
      of studied pharmaceuticals was studied through natural organic matter effects on
      single component and mixture systems.

PMID- 29173088
TI  - Reliability and concurrent validity of a motor skill competence test among 4- to
      12-year old children.
AB  - The purpose of this study was to examine the test-retest reliability, internal
      consistency and concurrent validity of the Athletic Skills Track (AST). During a
      regular PE lesson, 930 4- to 12-year old children (448 girls, 482 boys) completed
      two motor skill competence tests: (1) the Korperkoordination-Test fur Kinder
      (KTK) and (2) an age-related version of the AST (age 4-6 years: AST-1, age 6-9
      years: AST-2, and age 9-12 years: AST-3). The test-retest reliability of the AST
      was high (AST-1: ICC = 0.881 (95% CI: 0.780-0.934); AST-2: ICC = 0.802 (95% CI:
      0.717-0.858); and AST-3: ICC = 0.800 (95% CI: 0.669-0.871). The internal
      consistency, concerning the three age-bands of the AST was above the acceptable
      level of Cronbach's alpha > 0.70 (AST-1: alpha = 0.764; AST-2: alpha = 0.700; and
      AST-3: alpha = 0.763). There was a moderate to high correlation between the time
      to complete the AST, and the age- and gender-related motor quotients of the KTK
      (AST-1: r = -0.747, p = 0.01; AST-2: r = -0.646, p = 0.01; and AST-3: r = -0.602,
      p = 0.01). The Athletic Skills Track is a reliable and valid assessment tool to
      assess motor skill competence among 4- to 12-year old children in the PE setting.

PMID- 29173089
TI  - Interpersonal needs and psychological pain: The role of brooding and rejection
      sensitivity.
AB  - The interpersonal theory of suicide proposes that thwarted belongingness (TB) and
      perceived burdensomeness (PB) predict psychological pain and desire for suicide.
      Brooding may be a mechanism in explaining how TB and PB predict pain. The
      conceptual similarity between rejection sensitivity (RS) and TB suggests that
      individuals with high RS may be likely to experience psychological pain in the
      context of TB. To test this model, 155 college students completed measures of
      psychological pain, TB, PB, brooding, and RS. As predicted, brooding mediated the
      relations between both TB and PB and psychological pain. RS interacted with TB in
      predicting psychological pain.

PMID- 29173090
TI  - Zebrafish Transcription Factor ORFeome for Gene Discovery and Regulatory Network
      Elucidation.
AB  - The completion of the zebrafish genome sequence and advances in miniaturization
      and multiplexing were essential to the creation of techniques such as RNA-seq,
      ChIP-seq, and high-throughput behavioral and chemical screens. Multiplexing was
      also instrumental in the recent enhancement of the classic yeast one-hybrid
      interaction techniques to provide unprecedented discovery capabilities for
      protein-DNA interactions. Unfortunately its use for zebrafish research is
      currently hampered by the lack of an open reading frame (ORF) clone collection.
      As a first step toward a complete collection, we describe a small library of
      transcriptional regulatory proteins comprising 142 ORFs and its potential
      applications.

PMID- 29173091
TI  - Molecular aspects of core-shell intrinsic defect induced enhanced antibacterial
      activity of ZnO nanocrystals.
AB  - AIM: To investigate molecular aspects of the antibacterial effect of size
      dependent core-shell intrinsic defects of nanocrystalline ZnO synthesized through
      high energy ball milling technique. MATERIALS & METHODS: Mechanically synthesized
      and characterized 7, 10 and 15 h milled ZnO nanoparticles were evaluated for
      antibacterial activity with molecular investigation by computational molecular
      docking. RESULTS: Synthesized ZnO nanoparticles displayed shrinkage of core and
      increase of shell with reduction in size of bulk ZnO particles from 250 to 80, 40
      and 20 nm and increase in zeta potential up to -19 mV in 7, 10 and 15 h nano ZnO.
      Antibacterial activity was found increased with decrease in size due to increased
      reactive oxygen species and membrane damage in bacteria. CONCLUSION: Synthesized
      nano ZnO exhibit size-dependent antibacterial action as consequences of
      interactions with cell membrane proteins via hydrogen bond interaction with amino
      acid residues followed by internalization, membrane depolarization and induction
      of reactive oxygen species generation.

PMID- 29173092
TI  - Ergogenic effects of precooling with cold water immersion and ice ingestion: A
      meta-analysis.
AB  - This review evaluated the effects of precooling via cold water immersion (CWI)
      and ingestion of ice slurry/slushy or crushed ice (ICE) on endurance performance
      measures (e.g. time-to-exhaustion and time trials) and psychophysiological
      parameters (core [Tcore] and skin [Tskin] temperatures, whole body sweat [WBS]
      response, heart rate [HR], thermal sensation [TS], and perceived exertion [RPE]).
      Twenty-two studies were included in the meta-analysis based on the following
      criteria: (i) cooling was performed before exercise with ICE or CWI; (ii)
      exercise longer than 6 min was performed in ambient temperature >=26 degrees C;
      and (iii) crossover study design with a non-cooling passive control condition.
      CWI improved performance measures (weighted average effect size in Hedges' g [95%
      confidence interval] + 0.53 [0.28; 0.77]) and resulted in greater increase
      (DeltaEX) in Tskin (+4.15 [3.1; 5.21]) during exercise, while lower peak Tcore (
      0.93 [-1.18; -0.67]), WBS (-0.74 [-1.18; -0.3]), and TS (-0.5 [-0.8; -0.19]) were
      observed without concomitant changes in DeltaEX-Tcore (+0.19 [-0.22; 0.6]), peak
      Tskin (-0.67 [-1.52; 0.18]), peak HR (-0.14 [-0.38; 0.11]), and RPE (-0.14 [
      0.39; 0.12]). ICE had no clear effect on performance measures (+0.2 [-0.07;
      0.46]) but resulted in greater DeltaEX-Tcore (+1.02 [0.59; 1.45]) and DeltaEX
      Tskin (+0.34 [0.02; 0.67]) without concomitant changes in peak Tcore (-0.1 [
      0.48; 0.28]), peak Tskin (+0.1 [-0.22; 0.41]), peak HR (+0.08 [-0.19; 0.35]), WBS
      (-0.12 [-0.42; 0.18]), TS (-0.2 [-0.49; 0.1]), and RPE (-0.01 [-0.33; 0.31]).
      From both ergogenic and thermoregulatory perspectives, CWI may be more effective
      than ICE as a precooling treatment prior to exercise in the heat.

PMID- 29173093
TI  - Molecular network-selected pharmacogenomics in a case of bipolar spectrum
      disorder.
AB  - Personal genomic analysis was used for molecular diagnosis and pharmacogenomics
      in a 53-year-old female suffering from alternating depressive and dysphoric
      episodes. A total of 52 genes and 108 SNPs were analyzed in the whole genome.
      Results from the pharmacogenomic analysis were consistent with the
      pharmacological history and indicate mutations associated with low monoaminergic
      tone, but also a hyperactive 5HT2A receptor, a feature that associates to a high
      probability of developing a bipolar condition, especially under 5
      hydroxytryptamine potentiating pharmacology. This aligns with the patient
      developing dysphoria with high clomipramine. The pharmacokinetic genomics pointed
      out to some absorption, distribution, metabolism, and excretion (ADME)
      alterations that can lower or nullify drug's activity. A personalized regimen was
      proposed, with a positive outcome after 1 year.

PMID- 29173094
TI  - Improving efficiency of an angiotensin converting enzyme inhibitory peptide as
      multifunctional peptides.
AB  - Bioactive peptides have been defined as specific protein fragments that have
      numerous biological activities. The aim of this study was to introduce three
      multifunctional peptides. Hence, we used rabbit lung angiotensin converting
      enzyme (ACE) inhibitor peptide AFKDEDTEEVPFR to prepare two analogous peptides
      KDEDTEEVP and KDEDTEEVH. ACE inhibitory, antioxidant, and antimicrobial
      activities of three synthetic peptides were investigated. Among the three
      peptides, KDEDTEEVP exhibited the highest ACE inhibitory activity with IC50 value
      of 69.63 +/- 2.51 MUM. Furthermore, the results of fluorescence spectroscopy and
      molecular modeling showed that KDEDTEEVP had more affinity to ACE than other
      peptides. The peptide of KDEDTEEVH showed the strongest antioxidant scavenging
      capacity on DPPH radicals (EC50 = 135 +/- 9.62 MUM), hydroxyl radicals (EC50 =
      144 +/- 8.73 MUM), and ABTS radicals (EC50 = 62 +/- 4.52%). Moreover, it showed
      the highest activity in iron-chelating test (EC50 = 226 +/- 14.13 MUM) and could
      also effectively inhibit the peroxidation of linoleic acid. The antimicrobial
      activity results showed that KDEDTEEVH had higher efficiency against Gram
      positive than Gram-negative bacteria with MIC values of higher than 205 +/- 10.75
      MUM. Although there was not a direct correlation between ACE inhibitor and
      antioxidant activity for analogous peptides, both analogous peptides exhibited
      more efficiency than the mother peptide. Thus, they can be considered as
      multifunctional peptides and would be beneficial ingredient to be used in food
      and drug industry.

PMID- 29173095
TI  - Seasonal variation of cancer mortality in Hungary between 1984 and 2013.
AB  - AIMS: Despite decreasing trends, Hungary is the leader in cancer mortality among
      European countries. We examined the seasonal variation of cancer mortality in
      Hungary between 1984 and 2013. METHODS: Hungarian monthly cancer mortality and
      population data were used in the analysis. The Walter-Elwood method was used to
      determine seasonal variation in both mortality rates and proportionate mortality.
      RESULTS: Significant winter-peak seasonality was found in all-cancer mortality. A
      similar seasonal trend with a peak from November to January was observed in death
      rates from colorectal, lung, female breast, prostate, bladder, brain, lymphoid
      and hematopoietic cancers. However, no more cyclical variation was identified in
      the mortality rates from other cancers. In addition, significant seasonal
      variation in proportionate mortality was shown for all cancer sites examined,
      with a peak in August or September. CONCLUSIONS: This study presents the
      seasonality pattern of different types of cancer mortality which might be related
      to environmental factors (e.g. infections).

PMID- 29173096
TI  - Death in life or life in death? Dementia's ontological challenge.
AB  - Is it possible to end one's life well with dementia? The perception of dementia
      as death brought into life flows from ideas about humanness embedded in
      medicine's Cartesian paradigm. Dementia as incurable brain disease exacerbates
      negativity. But the real impact of dementia is that it changes social relations:
      to live well with dementia requires a relational not Cartesian understanding of
      life. A relational ontology prioritizes social health: to live is to be held in
      connection. Negativity produces the disconnection that is death, with or without
      disease. When people with dementia are held in connection, they live a better
      life.

PMID- 29173097
TI  - Understanding grief in children who have lost a parent with cancer: How do they
      give meaning to this experience? Results of an interpretative phenomenological
      analysis.
AB  - Though the adjustment of bereaved children is increasingly investigated through
      quantitative studies, their intimate representations regarding the loss of their
      parent remain unknown. This qualitative study aims at exploring how they give
      meaning to this experience. Nondirective interviews with bereaved children were
      conducted and submitted to an interpretative phenomenological analysis. Fourteen
      children (8 boys, 6 girls, mean age = 8.5 years) were recruited. Seven major
      themes depicting their grief experience were identified. The importance of the
      surviving parent is critically highlighted. Findings suggest that the remaining
      parent could become a fundamental actor in providing grief support for the
      bereaved children.

PMID- 29173098
TI  - Reverse syphilis screening algorithm fails to demonstrate cost effectiveness in
      persons living with HIV.
AB  - Although the reverse syphilis screening algorithm is more efficient than the
      traditional algorithm, it may lead to exorbitant costs for health systems serving
      persons living with HIV needing annual syphilis screening. Alternatively, the
      traditional screening algorithm is cost saving in many scenarios.

PMID- 29173099
TI  - Are the bite force and electromyographic activity altered in muscle TMD patients
      with abfraction lesions?
AB  - OBJECTIVE: To verify if the maximal molar bite force (BF) and the
      electromyographic activity (EMG) are altered in TMD patients with abfraction
      lesions (AL) when compared to those without AL. METHODS: The sample was composed
      of 45 patients (18-60 years old), 30 diagnosed with TMD (RDC/TMD) (15 with AL and
      15 without AL) and 15 controls. The BF and the EMG of the masticatory muscles
      (maximal voluntary contraction (MVC) and chewing gum) were measured. RESULTS: TMD
      patients showed decreased BF (p < 0.001), without differences between patients
      with and without AL. The electromyographic activity during MVC was similar among
      all groups (p > 0.05), although there was a greater trend of muscular balance for
      the control group (percentage overlapping coefficient and electromyographic
      indexes). The TMD group without AL showed a lower number of cycles and
      masticatory frequency. DISCUSSION: TMD patients with and without AL exhibited
      similar results in the analysis of the BF and EMG, without differences.

PMID- 29173100
TI  - Wastewater treatment with a new electrically enhanced biomass concentrator
      reactor: trial application and technological perspectives.
AB  - Biomass concentrator reactors (BCRs) are an alternative wastewater treatment
      technology developed as a possible solution to membrane bioreactors' (MBRs) high
      construction and energetic costs. BCRs are an alternative based on the same
      principle of biomass retention, using a coarser filter medium instead of a
      membrane. A BCR-derived technology enhanced by an electric field called
      electrically enhanced biomass concentrator reactor (E2BCR) was developed,
      designed, and tested for wastewater treatment at different organic loads for a
      period of 100 days. The electrically enhanced reactor showed better chemical
      oxygen demand (COD) removal performances that the non-enhanced control reactor
      (90% and 84%, respectively), and a lower fouling tendency. The E2BCR proved to be
      more energy efficient in comparison with the control reactor in terms of energy
      consumption per mass of COD removed.

PMID- 29173101
TI  - Advancing Global Precision Medicine: An Overview of Genomic Testing and
      Counseling Services in Malaysia.
AB  - Precision medicine, genomic and diagnostic services are no longer limited to
      developed countries. This broadening in geography of biomarker applications and
      omics diagnostics also demands empirical study of implementation, diagnostic
      testing, and counseling practices in the field. For example, the Malaysian
      population has large ethnic diversity and high prevalence of genetic disorders
      such as hemoglobinopathies and metabolic disorders. Increased morbidity and
      mortality from such diseases have a direct impact on society and health system
      sustainability and for this, decision-making becomes of outmost importance. We
      report here on our findings on the landscape of genomic testing and genetic
      counseling services in Malaysia. We first defined the framework of all Malaysian
      stakeholders that offer genomics services and next, we identified the related
      information gaps, as depicted through the service providers' online websites. Our
      research framework revealed that there is a very diverse spectrum of genomics
      services in Malaysia, in which wet- and dry-laboratory services integrate.
      Moreover, we identify the current gaps and possible remedies to improve the
      quality of genomic and predictive analytics, not to mention considerations to
      ensure robust ethics and responsible innovation. To our knowledge, this is the
      first such study to be performed for a Southeast Asian country. Our genomics and
      precision medicine services mapping strategy presented in this study may serve as
      a model for field assessment at regional, national, and international levels as
      precision medicine is expanding globally and new governance challenges and
      opportunities continue to emerge for smart implementation science.

PMID- 29173102
TI  - MoKey: A versatile exergame creator for everyday usage.
AB  - Currently, virtual applications for physical exercises are highly appreciated as
      rehabilitation instruments. This article presents a middleware called "MoKey"
      (Motion Keyboard), which converts standard off-the-shelf software into exergames
      (exercise games). A configurable set of gestures, captured by a motion capture
      camera, is translated into the key strokes required by the chosen software. The
      present study assesses the tool regarding usability and viability on a
      heterogeneous group of 11 participants, aged 5 to 51, with moderate to severe
      disabilities, and mostly bound to a wheelchair. In comparison with FAAST (The
      Flexible Action and Articulated Skeleton Toolkit), MoKey achieved better results
      in terms of ease of use and computational load. The viability as an exergame
      creator tool was proven with help of four applications (PowerPoint(r), e-book
      reader, Skype(r), and Tetris). Success rates of up to 91% have been achieved,
      subjective perception was rated with 4.5 points (from 0-5). The middleware
      provides increased motivation due to the use of favorite software and the
      advantage of exploiting it for exercise. Used together with communication
      software or online games, social inclusion can be stimulated. The therapists can
      employ the tool to monitor the correctness and progress of the exercises.

PMID- 29173103
TI  - Social Norm, Family Communication, and HBV Screening among Asian Americans.
AB  - Individuals' behaviors are influenced by those of others in their social
      environment (i.e., descriptive norms), as well as by how individuals perceive
      they should behave in that environment (e.g., injunctive norms). Although social
      norms are thought to play an important role in hepatitis B virus (HBV) screening,
      limited theoretical or empirical guidance exists on how the underlying process
      works. In addition, norms are social phenomena that are spread through family
      discussion about the importance of getting HBV screening. Using the theory of
      normative social behavior (TNSB), this study examined the roles of injunctive
      norms (IN), descriptive norms (DN), and family discussion in HBV screening
      behavior among Asian Americans. Data from a survey of Asian Americans in the
      Baltimore Washington metropolitan area (N = 877) were used to test underlying
      theoretical propositions. DN and family discussion emerged as key factors in HBV
      screening behavior among all Asian Americans. IN were associated with HBV
      screening among Chinese and Korean Americans, but not for Vietnamese Americans.
      Family discussion moderated the influence of DN on behavior among Chinese and
      Vietnamese Americans. However, the main effect of DN on screening behavior was
      not modified by IN (no interactions between DN and IN). The results indicate that
      family discussion and social norms are integral in enabling Asian Americans to
      undergo HBV screening and warrant sensitivity in the design and implementation of
      a liver cancer prevention program in this high-risk group of Asian Americans.

PMID- 29173104
TI  - Examining the Influence of Relational Aggression on Sexual Satisfaction With
      Attachment Behaviors as a Potential Mediator.
AB  - The purpose of this study was to investigate the relationship between relational
      aggression and sexual satisfaction, as well as to determine if attachment
      behaviors could mediate this relationship. Data came from the Relate Institute
      Questionnaire (RELATE) and were drawn from the matched-pair responses of 539
      heterosexual married couples. Results showed the greater the perceived relational
      aggression, the lower the sexual satisfaction for both self and partner,
      regardless of gender. Mediation analyses suggest that attachment behaviors may be
      a mechanism through which relational aggression influences sexual satisfaction.
      Implications for clinicians and future research are discussed.

PMID- 29173105
TI  - Economic Evaluation of Teledentistry in Cleft Lip and Palate Patients.
AB  - OBJECTIVE: To assess the use of Teledentistry (TD) in delivering specialist
      dental services at the Royal Children's Hospital (RCH) for rural and regional
      patients and to conduct an economic evaluation by building a decision model to
      estimate the costs and effectiveness of Teledental consultations compared with
      standard consultations at the RCH. METHODS: A model-based analysis was conducted
      to determine the potential costs of implementing TD at the RCH. The outcome
      measure was timely consultations (whether the patient presented within an
      appropriate time according to the recommended schedule). Dental records at the
      RCH of those who presented for orthodontic or pediatric dental consultations were
      assessed. A cost-effectiveness analysis (CEA), comparing TD with the traditional
      method of consultation, was conducted. One-way sensitivity analysis was performed
      to test the robustness of the results. Results and Materials: A total of 367 TD
      appropriate consultations were identified, of which 241 were timely (65.7%). The
      mean cost of a RCH consultation was A$431.29, with the mean TD consult costing
      A$294.35. This represents a cost saving of A$136.95 per appointment. The CEA
      found TD to be a dominant option, with cost savings of A$3,160.81 for every
      additional timely consult. The model indicated that 36.7 days of clinic time may
      be freed up at the RCH to treat other patients and expand capacity. These results
      were robust when performing one-way sensitivity analysis. CONCLUSION: When taking
      a societal perspective, the implementation of TD is likely to be a cost-effective
      alternative compared with the standard practice of face-to-face consultation at
      the RCH.

PMID- 29173106
TI  - Biodegradation of high concentrations of formaldehyde using Escherichia coli
      expressing the formaldehyde dismutase gene of Methylobacterium sp. FD1.
AB  - In the present study, formaldehyde dismutase from Methylobacterium sp. FD1 was
      partially purified and analyzed by nanoLC-MS/MS; it was then cloned from the
      genomic DNA of FD1 by PCR. The open reading frame of the formaldehyde dismutase
      gene of FD1 was estimated to be 1203 bp in length. The molecular weight and pI of
      formaldehyde dismutase (401 aa), as deduced from the FD1 gene, were calculated at
      42,877.32 and 6.56, respectively. NAD(H)-binding residues and zinc-binding
      residues were found in the amino acid sequence of the deduced formaldehyde
      dismutase of FD1 by BLAST search. The resting Escherichia coli cells that were
      transformed with the FD1 formaldehyde dismutase gene degraded high concentrations
      of formaldehyde and produced formic acid and methanol that were molar equivalents
      of one-half of the degraded formaldehyde. The lyophilized cells of the
      recombinant E. coli also degraded high concentrations of formaldehyde.

PMID- 29173107
TI  - Does Eliminating the Earnings Test Increase the Incidence of Low Income Among
      Older Women?
AB  - Reducing or eliminating Social Security's retirement earnings test (RET) can
      encourage labor supply of older individuals receiving benefits. However, these
      reforms can encourage earlier claiming of Social Security benefits, permanently
      lowering future benefits. We explore the consequences, for older women, of
      eliminating the RET from the full retirement age to age 69 (in 2000), relying on
      the intercohort variation in exposure to changes in the RET to estimate these
      effects. The evidence is consistent with the conclusion that eliminating the RET
      increased the likelihood of having very low incomes among women in their mid-70s
      and older-ages at which the lower benefits from claiming earlier could outweigh
      higher income in the earlier period when women or their husbands increased their
      labor supply.

PMID- 29173108
TI  - Effects of image congruency on persuasiveness and recall in direct-to-consumer
      prescription drug advertising.
AB  - Although direct-to-consumer (DTC) prescription drug advertising is regulated by
      the U.S. Food and Drug Administration, content analyses suggest advertisers may
      not disclose drug risks in the same way they describe drug benefits. This study
      tests the relationship between image congruency in televised DTC advertisements,
      recall of risks/benefits, and perceived persuasiveness. Advertisements for
      Nasonex, Advair, and Lunesta were shown to college students in either their
      original (image incongruent) or modified (image neutral) form. Risks were easier
      to recall with image-neutral advertisements. Gender also had a significant
      interaction effect, suggesting that males and females process DTC advertisement
      differently.

PMID- 29173110
TI  - How does objective and subjective human papillomavirus knowledge affect
      information-seeking intentions and source preferences?
AB  - This study examines the effects of objective (factual information) and subjective
      knowledge (an individual's self-assessment of how much knowledge they have) on
      information-seeking intentions and source preferences. It explores the human
      papillomavirus (HPV) knowledge inequalities in groups of young adults age 18-26
      years with and without vaccinations and diagnosis, and different
      demographics/socio-economic and perceptions of health status. Higher subjective
      HPV knowledge leads to greater information-seeking intentions from family/friends
      and mass media but not from health professionals and the Internet. Objective HPV
      knowledge did not matter for information seeking. The important role of
      demographics/socio-economic and perceived health status is also discussed.

PMID- 29173109
TI  - Strategies for recruiting populations to participate in the chronic disease self
      management program (CDSMP): A systematic review.
AB  - The purpose of this review was to better understand how to market the Chronic
      Disease Self-Management Program to new audiences. Eight databases were searched
      for peer-reviewed studies of the CDSMP. A total of 39 articles were analyzed to
      describe the theoretical basis of recruitment strategies and their effectiveness
      while engaging diverse populations. Findings included that female, Caucasian, and
      elderly groups are overrepresented in CDSMP literature and recruitment efforts
      have not been explicitly grounded in theory. This review provides insight into
      trends in CDSMP recruitment and identifies the need for further research
      regarding the application of marketing theory to future enrollment efforts.

PMID- 29173112
TI  - "We want to offer you peace of mind": Marketing of transnational commercial
      surrogacy services to intended parents.
AB  - The purpose of this research study was to conduct a content analysis of
      commercial surrogacy websites to explore how surrogacy is marketed to intended
      parents. The researchers developed a template to code website data, and a total
      of 345 website pages were reviewed. Websites depicted surrogacy as a solution to
      a problem, privileged genetic parenthood, ignored the potential for exploitation,
      dismissed surrogates' capacity to bond with the fetuses they carry, emphasized
      that surrogacy arrangements are mutually beneficial, ignored structural
      inequalities, and depicted surrogates as conforming to strict gender roles. These
      framings introduce vulnerabilities to both intended parents and surrogate
      mothers.

PMID- 29173113
TI  - Posterior reversible encephalopathy syndrome possibly induced by pemetrexed
      maintenance therapy for lung cancer: a case report and literature review.
AB  - Introduction Advances in systemic chemotherapy, molecular targeted therapy and
      immunotherapy have extended and improved the quality of life of patients with
      cancer. However, the central nervous system is very susceptible to complications
      of systemic cancer and its treatment. Posterior reversible encephalopathy
      syndrome (PRES) is a rare clinical and neuroradiologic entity which has garnered
      increasing recognition in the past two decades. Cancer patients are generally
      treated with cytotoxic agents, immunotherapy, molecular targeted therapies or
      glucosteroids which are more frequently associated with PRES. Case presentation A
      59-year old female, known with a relapse of her lung adenocarcinoma, had been
      treated with 4 cycles of cisplatin (75 mg/m2) and pemetrexed (500 mg/m2). Six
      weeks after this combination chemotherapy and within 28 h after the
      administration of pemetrexed maintenance therapy, she developed a generalised
      epileptic insult. Magnetic resonance imaging (MRI) of the brain showed bilateral
      areas of increased signal intensity in the subcortical parietal and frontal white
      matter. She was treated with a broad spectrum antiseizure drug, levetiracetam 750
      mg twice daily and strict control of blood pressure. Discussion Diagnosis of PRES
      should be considered in all patients with neurologic symptoms who are at risk to
      develop PRES. It is crucial to establish the diagnosis as soon as possible since
      there is no specific treatment of PRES other than correction of the underlying
      risk factors and preventing seizure recurrence. Administration of pemetrexed is a
      possible risk factor for the development of PRES.

PMID- 29173115
TI  - Nitroguanidine (NQ) (2016).
AB  - 1-Nitroguanine (NG), also known as picrate, guanidine nitro, and N'
      nitroguanidine, is used by the military as a propellant. Oral rodent LD50 data
      are generally >5000 mg/kg. NG is neither an eye nor a skin irritant, and it is
      not a skin sensitizer. NG is not genotoxic. No inhalation data are available;
      however, there are data from both 14- and 90-day oral (feed) toxicity studies in
      male and female Sprague Dawley rats at dosages up to 1000 mg/kg/day. There were
      no deaths on these studies and the only effect considered possibly related to
      treatment was decreased weight in females at the high-dose level in the 90-day
      study. Mice at similar dosages were even less affected. The NOAEL for both rats
      and mice (oral) was 316 mg/kg/day. There was no evidence of developmental
      toxicity in Sprague-Dawley rats administered NG by oral gavage, and the free
      standing NOAEL was 1000 mg/kg with material toxicity. In Wistar rats, there was
      high mortality (50%) at 500 mg/kg NG administered by oral gavage; there was
      decreased body weight, feed consumption, and notable clinical signs in the dams
      at this dose level. Fetal toxicity could not be determined in this group. NG
      demonstrated maternal toxicity at 1000 mg/kg in rabbits; however, there were no
      evident differences in the rate of fetal malformations across the test groups. A
      NOAEL of 316 mg/kg was identified for maternal and fetal toxicity in this study.
      In a two-generation study, it was concluded the NG did not cause reproductive or
      fertility effects at dosages up to 1000 mg/kg/day. Absorption was rapid, non-dose
      dependent, and resulted in an apparent volume of distribution (VD) of between
      0.66 (IV) and 0.85-0.87 (oral) l/kg. Elimination was primarily through the urine
      as unchanged compound. Human experience with NG dates back 100 years; however, no
      actual studies on humans have been reported. Non-military uses include automotive
      airbags, anti-corrosive coatings, and pharmaceutical manufacturing. The point of
      departure for Workplace Environmental Exposure Level (WEEL) derivations was 316
      mg/kg, and a WEEL of 7 mg/m3 as an 8-h time-weighted average (TWA) was
      recommended.

PMID- 29173114
TI  - A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in
      Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 1 of 2).
AB  - Spontaneous rodent progressive cardiomyopathy (PCM) in the Sprague Dawley rat may
      confound identification and/or interpretation of potential test article (TA)
      related cardiotoxicity. Pathologists apply diagnostic term(s) and thresholds for
      diagnosing and assigning severity grades for PCM and/or PCM-like (PCM/like)
      lesions consistently within a study, which is necessary to identify and interpret
      TA-related findings. Due to differences in training and/or experiences,
      diagnostic terms and thresholds may vary between pathologists. Harmonized
      terminology and thresholds across studies will generate better historical control
      data, will likely enhance interpretation of study data, and may further enhance
      our understanding of the spontaneous change. An assessment of the diagnostic
      approaches of a group of 37 pathologists identified an approach that is
      relatively easily applied; and if adopted, it could enhance diagnostic
      consistency across studies. This approach uses the single "slash" term
      "necrosis/inflammatory cell infiltrate (NICI)" as the diagnosis for the spectrum
      of lesions seen in younger rats, uses no threshold for diagnosis (e.g., diagnose
      all lesions clearly identifiable as PCM/like), and uses aggregate lesion size of
      approximately >=45% of the field of view (FOV) using a 10*/22 eyepiece and the
      40* objective or approximately >=100% of the FOV using the 60* objective as the
      criterion separating minimal from mild severities.

PMID- 29173116
TI  - 3-Nitro-1,2,4-triazol-5-one (2014).
AB  - 3-Nitro-1,2,4-triazol-5-one (NTO) is a potential replacement for energetics in
      military munitions. It is a component of IMX-101, a munition designed to prevent
      unintentional detonation. This report summarizes the dermal, oral, and inhalation
      animal toxicity data, including the results of genotoxicity and limited
      reproductive and developmental studies. NTO has an acute LD50 in rats and mice of
      >5000 mg/kg, is a potential eye and skin irritant, but does not induce skin
      sensitization. Acute inhalation toxicity studies in rats were negative, but
      testicular hypoplasia was observed in a 14-day oral study in rats administered
      NTO at >500 mg/kg/day. Similar findings were noted in an oral 90-day study at
      dosages >315 mg/kg/day and in reproductive toxicity studies at >125 mg/kg/day.
      NTO did not cause any developmental defects. All genotoxicity studies were
      negative. ADME and pharmacokinetics data showed rapid uptake and elimination of
      NTO from both inhalation and oral intakes. Biotransformation by liver microsomes
      demonstrated two separate pathways, one aerobic and the other anaerobic. NTO is
      not considered an endocrine disruptor. There is very little human data regarding
      NTO or the IMX-101 mixtures. Using testicular changes in rats as the point of
      departure for deriving a Workplace Environmental Exposure Level (WEEL) for NTO,
      the resulting BMDL10 was 40 mg/kg/day, and the 8-hour time-weighted average was 2
      mg/m2.

PMID- 29173117
TI  - Psychosocial risks of prescription drug misuse among U.S. racial/ethnic
      minorities: A systematic review.
AB  - Prescription drug misuse (PDM) is the leading cause of accidental death in the
      U.S. One in five Americans report at least one lifetime incident of PDM. PDM has
      been studied extensively, yet there is limited inclusion of racial/ethnic
      minorities due to purportedly lower rates of PDM. However, health disparate
      groups often face more detrimental consequences of substance abuse including
      behavioral, social, and medical/mental health (e.g., injury, HIV/AIDS,
      incarceration, educational attainment, and comorbidity). Failing to characterize
      risk factors for and consequences of PDM in racial/ethnic minorities may mask the
      disproportionate negative impact of this epidemic. This systematic review of
      three research indexes revealed 28 peer-reviewed studies published on PDM in
      racial/ethnic minority adults. Results indicated a high prevalence of PDM among
      veterans, bisexual and gay young adults, and substance abusers compared to the
      general population. Demographic correlates of PDM included younger age, male
      gender, less educated, unmarried, and those with health/emotional issues. Rates
      of PDM in demographically vulnerable populations suggest that broadening
      inclusiveness in PDM research, interventions, and clinical practice is
      imperative.

PMID- 29173118
TI  - MicroCT-Based Phenomics in the Zebrafish Skeleton Reveals Virtues of Deep
      Phenotyping in a Distributed Organ System.

PMID- 29173119
TI  - Contact area affects frequency-dependent responses to vibration in the peripheral
      vascular and sensorineural systems.
AB  - Repetitive exposure to hand-transmitted vibration is associated with development
      of peripheral vascular and sensorineural dysfunctions. These disorders and
      symptoms associated with it are referred to as hand-arm vibration syndrome
      (HAVS). Although the symptoms of the disorder have been well characterized, the
      etiology and contribution of various exposure factors to development of the
      dysfunctions are not well understood. Previous studies performed using a rat-tail
      model of vibration demonstrated that vascular and peripheral nervous system
      adverse effects of vibration are frequency-dependent, with vibration frequencies
      at or near the resonant frequency producing the most severe injury. However, in
      these investigations, the amplitude of the exposed tissue was greater than
      amplitude typically noted in human fingers. To determine how contact with
      vibrating source and amplitude of the biodynamic response of the tissue affects
      the risk of injury occurring, this study compared the influence of frequency
      using different levels of restraint to assess how maintaining contact of the tail
      with vibrating source affects the transmission of vibration. Data demonstrated
      that for the most part, increasing the contact of the tail with the platform by
      restraining it with additional straps resulted in an enhancement in transmission
      of vibration signal and elevation in factors associated with vascular and
      peripheral nerve injury. In addition, there were also frequency-dependent
      effects, with exposure at 250 Hz generating greater effects than vibration at
      62.5 Hz. These observations are consistent with studies in humans demonstrating
      that greater contact and exposure to frequencies near the resonant frequency pose
      the highest risk for generating peripheral vascular and sensorineural
      dysfunction.

PMID- 29173120
TI  - Living, dying, after death: Achieving a "good" death in the time of AIDS orphan
      care.
AB  - AIDS has devastated communities across southern Africa, leaving many children
      orphaned. Grandmothers are considered ideal caregivers because of cultural
      expectations of intergenerational care, and because they have not been decimated
      by AIDS to the same extent as younger adults. However, these grandmothers, who
      currently carry the majority of the burden of care for AIDS orphans, are
      themselves aging and dying. I argue here that in Lesotho, the caregiving demanded
      of grandmothers late into their lives not only alters kin relations for the
      living but has increasingly made a "good" death unachievable for elderly
      caregivers.

PMID- 29173122
TI  - Are Study and Journal Characteristics Reliable Indicators of "Truth" in Imaging
      Research?
AB  - Purpose To evaluate whether journal-level variables (impact factor, cited half
      life, and Standards for Reporting of Diagnostic Accuracy Studies [STARD]
      endorsement) and study-level variables (citation rate, timing of publication, and
      order of publication) are associated with the distance between primary study
      results and summary estimates from meta-analyses. Materials and Methods MEDLINE
      was searched for meta-analyses of imaging diagnostic accuracy studies, published
      from January 2005 to April 2016. Data on journal-level and primary-study
      variables were extracted for each meta-analysis. Primary studies were
      dichotomized by variable as first versus subsequent publication, publication
      before versus after STARD introduction, STARD endorsement, or by median split.
      The mean absolute deviation of primary study estimates from the corresponding
      summary estimates for sensitivity and specificity was compared between groups.
      Means and confidence intervals were obtained by using bootstrap resampling; P
      values were calculated by using a t test. Results Ninety-eight meta-analyses
      summarizing 1458 primary studies met the inclusion criteria. There was
      substantial variability, but no significant differences, in deviations from the
      summary estimate between paired groups (P > .0041 in all comparisons). The
      largest difference found was in mean deviation for sensitivity, which was
      observed for publication timing, where studies published first on a topic
      demonstrated a mean deviation that was 2.5 percentage points smaller than
      subsequently published studies (P = .005). For journal-level factors, the
      greatest difference found (1.8 percentage points; P = .088) was in mean deviation
      for sensitivity in journals with impact factors above the median compared with
      those below the median. Conclusion Journal- and study-level variables considered
      important when evaluating diagnostic accuracy information to guide clinical
      decisions are not systematically associated with distance from the truth;
      critical appraisal of individual articles is recommended. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 29173121
TI  - Fueling for Performance.
AB  - CONTEXT: Proper nutrition is crucial for an athlete to optimize his or her
      performance for training and competition. Athletes should be able to meet their
      dietary needs through eating a wide variety of whole food sources. EVIDENCE
      ACQUISITION: PubMed was searched for relevant articles published from 1980 to
      2016. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: An
      athlete should have both daily and activity-specific goals for obtaining the fuel
      necessary for successful training. Depending on the timing of their season,
      athletes may be either trying to gain lean muscle mass, lose fat, or maintain
      their current weight. CONCLUSION: An athlete will have different macronutrient
      goals depending on sport, timing of exercise, and season status. There are no
      specific athletic micronutrient guidelines, but testing should be considered for
      athletes with deficiency or injury. Also, some athletes who eliminate certain
      whole food groups (eg, vegetarian) may need to supplement their diet to avoid
      deficiencies.

PMID- 29173123
TI  - Screening Digital Mammography Recall Rate: Does It Change with Digital Breast
      Tomosynthesis Experience?
AB  - Purpose To compare screening mammography recall rate, cancer detection rate
      (CDR), and positive predictive values (PPVs) for digital mammography before and
      after radiologist experience with digital breast tomosynthesis (DBT). Materials
      and Methods This retrospective study was approved by the institutional review
      board and compliant with HIPAA. The authors reviewed screening mammography audit
      data obtained from 2009 to 2014, during which 108 276 digital mammographic
      examinations were performed (50 062 before and 58 214 after experience with DBT).
      Recall rate, CDR, PPV of positive screening result (PPV1), PPV of biopsy
      recommendation (PPV2), and PPV of biopsies performed (PPV3) of digital
      mammography for six radiologists were compared before (2009-2011) and after (2012
      2014) experience with DBT. Radiologists worked in both a community setting, in
      which only digital mammography was available, and in two tertiary breast imaging
      centers, where they interpreted DBT images starting in 2012. Data were examined
      by using generalized linear mixed modeling wherein observations were nested for
      each radiologist over time. P < .05 was considered indicative of a statistically
      significant difference; 95% confidence intervals (CIs) were calculated. Results
      The average recall rate was 6.8% (range, 3.6%-9.7%) before experience with DBT
      and 7.9% (range, 5.5%-9.5%) after (P = .0316). Before experience with DBT, the
      recall rate increased only 0.01% for each year from 2009 to 2011 (P = .9727).
      After experience with DBT, the recall rate increased 0.65% for each year from
      2012 to 2014 (P < .0127). CDR increased from 2.5 per 1000 examinations (95% CI:
      2.2, 2.9) to 3.5 per 1000 examinations (95% CI: 3.0, 4.0; P = .0203). PPV2 and
      PPV3 increased significantly after experience with DBT, from 26.9% (95% CI:
      19.9%, 35.3%) to 36.1% (95% CI: 31.7%, 40.7%; P = .0212) for PPV2 and from 31.2%
      (95% CI: 24.0%, 39.3%) to 40.0% (95% CI: 35.5%, 44.6%; P = .0290) for PPV3.
      Conclusion Recall rate, CDR, PPV2, and PPV3 of digital mammography increased
      after radiologist experience with DBT. (c) RSNA, 2017.

PMID- 29173126
TI  - Racial bias in sport medical staff's perceptions of others' pain.
AB  - Unequal treatment based on race is well documented in higher education and
      healthcare settings. In the present work, we examine racial bias at the
      intersection of these domains: racial bias in pain-related perceptions among
      National Collegiate Athletic Association (NCAA) Division 1 sport medical staff.
      Using experimental vignettes about a student-athlete who injured his/her anterior
      cruciate ligament (ACL), we find, like prior work, that respondents perceived
      Black (vs. White) targets as having higher initial pain tolerance. Moreover, this
      bias was mediated by perceptions of social class. We extend prior work by showing
      racial bias was not evident on other outcome measures, including perception of
      recovery process pain, likelihood of over-reporting pain, and over-use of drugs
      to combat pain. This suggests stricter boundary conditions on bias in pain
      perceptions than had been previously recognized.

PMID- 29173125
TI  - Time-series analysis: variation of anti-acetylcholine receptor antibody titer in
      myasthenia gravis is related to incidence of Mycoplasma pneumoniae and influenza
      virus infections.
AB  - Objectives The exacerbating factors of myasthenia gravis (MG) are unknown.
      However, it has been speculated that infections may play a role in disease
      progression. Methods We calculated the adjusted anti-acetylcholine receptor
      antibody (Adj-AChR-Ab) titers (range, 0-1) in 58 MG patients between 2006 and
      2012. We determined the relationship between Adj-AChR-Ab titer and infection
      incidence. Results A cross-correlation function (CCF) analysis of Adj-AChR-Ab
      titer and incidence of Mycoplasma pneumoniae (M. pneumoniae) (r = 0.449, P <
      0.0001) and influenza virus (r = 0.411, P < 0.001) infections indicated
      significant correlations. MG with thymoma was highly correlated with M.
      pneumoniae infection (r = 0.798, P < 0.0001). The relative risk for Adj-AChR-Ab
      titer was 1.407 for M. pneumoniae (95% CI, 1.193-1.661 for an increase in one
      infected patient per monitoring point) and 1.158 for influenza (95% CI, 1.071
      1.253 for 100 infected patients). Conclusion Variation of Adj-AChR-Ab titer is
      significantly influenced by the presence of M. pneumoniae and influenza virus
      infections.

PMID- 29173127
TI  - Integrated Control of Nymphal Ixodes scapularis: Effectiveness of White-Tailed
      Deer Reduction, the Entomopathogenic Fungus Metarhizium anisopliae, and Fipronil
      Based Rodent Bait Boxes.
AB  - Pathogens transmitted by ticks are the leading cause of arthropod-associated
      human diseases in the United States and managing the risk of exposure to
      potentially infected ticks is of vital public health importance. A 3-year
      integrated tick management program to control blacklegged ticks, Ixodes
      scapularis, the primary vector for the pathogenic agents of Lyme disease, human
      anaplasmosis, and babesiosis, was implemented in the town of Redding in
      southwestern Connecticut beginning in 2013. Combinations of white-tailed deer,
      Odocoileus virginianus, reduction, area application of the entomopathogenic
      fungus Metarhizium anisopliae, and fipronil-based rodent bait boxes were
      evaluated for their ability to reduce nymphal I. scapularis over 3 years.
      Interference from local hunters prevented sufficient, sustained deer removal
      previously reported to negatively impact I. scapularis abundances (i.e., <5
      deer/km2). The combination of fipronil-based bait boxes and broadcast application
      of M. anisopliae had the most impact of any treatment combination; questing
      nymphs were reduced 78-95% within each year and Borrelia burgdorferi-infected
      questing nymphal I. scapularis encounter potential was reduced by 66% as compared
      with no treatment in the third year of the study. A combination of the broadcast
      application of M. anisopliae and small rodent-targeted fipronil-based bait boxes
      is an effective low-toxicity integrated approach that significantly reduced
      encounters with B. burgdorferi-infected questing nymphal I. scapularis on
      individual properties.

PMID- 29173128
TI  - Cognitive conflict resolution during psychotherapy: Its impact on depressive
      symptoms and psychological distress.
AB  - OBJECTIVE: The aim of this study was to assess the resolution of cognitive
      conflicts (CCs) within a randomized controlled trial testing the differential
      efficacy of group cognitive behavioral therapy (CBT) plus an individually
      tailored intervention module focused on CCs vs. group plus individual CBT, and to
      determine whether CC resolution was related to improvement in symptoms and
      psychological distress. METHODS: The data come from 104 adults meeting criteria
      for major depressive disorder and/or dysthymia. Change in scores on the Beck
      Depression Inventory-II and Clinical Outcomes in Routine Evaluation-Outcome
      Measure was assessed at the end of treatment and at three-month follow-up.
      Outcomes were compared between those participants who resolved their CCs and
      those who maintained them using three-level multilevel growth models. RESULTS: CC
      resolution did not depend on treatment allocation. Participants who resolved
      their CCs acquired greater benefits with regards to reduction of depressive
      symptoms and psychological distress than those who maintained their conflicts.
      CONCLUSIONS: CC seems to be a relevant notion to take into consideration to
      understand symptom improvement. Further research on CC might lead to the
      advancement of treatments which involve conflict resolution as a change
      mechanism.

PMID- 29173129
TI  - Preparation and performance of manganese-oxide-coated zeolite for the removal of
      manganese-contamination in groundwater.
AB  - A promising and easily prepared catalytic filler media, manganese-oxide-coated
      zeolite (MOCZ), for the removal of Mn (II) contamination in groundwater was
      studied. The optimal condition for MOCZ preparation was given as follows: acid
      activation of zeolite with 5% HCl mass percent for 12 h, then soaking of acid
      activated zeolite with 7% KMnO4 mass percent for 8 h, and finally calcination at
      300 degrees C for 5 h. Acid activation significantly enlarged the specific
      surface area of the zeolite (>79 m2 g-1), subsequently enhancing the coating of
      manganese oxides onto the surface of the zeolite. This was further supported by
      the manganese-to-zeolite ratio (gammaMn) and Energy dispersive analysis-mapping.
      The gammaMn was over 12.26 mg Mn g-1 zeolite, representing more active sites for
      the adsorption and catalytic-oxidation of Mn (II). As such, great performance of
      Mn (II) removal by MOCZ was obtained in the filter experiment. An estimated 98
      100% removal efficiency of Mn (II) was achieved in a greatly short startup time
      (only 2 h). During the filtration process, newborn flocculent manganese oxides
      with a mixed-valence of manganese (Mn (II) and Mn (IV)) were generated on the
      MOCZ surface, further facilitating the adsorption and catalytic-oxidation of Mn
      (II). The filter with MOCZ as adsorbent had a great performance on the Mn (II)
      removal in a wide range of hydraulic retention time (HRT) (4-40 min),
      particularly in a short HRT. Besides, the filter prolonged the filtration period
      (60 days), which would significantly reduce the frequency of backwash. Thus, it
      could be concluded that MOCZ prepared in this study showed a good performance in
      terms of Mn (II) removal in waterworks, especially small waterworks in the
      villages/towns.

PMID- 29173130
TI  - Erratum.

PMID- 29173131
TI  - Theorizing the lesbian hashtag: Identity, community, and the technological
      imperative to name the sexual self.
AB  - This analysis integrates poststructuralist and symbolic interactionist approaches
      to the self by incorporating the insights of science and technology studies
      regarding categorization processes. While the advent of the Internet has freed
      many individuals from geographical constraints on community formation, the
      architectures of online platforms produce a technological imperative to name
      aspects of the self with words. Using sexual identity hashtags on Instagram
      (e.g., #lesbian) thus performs paradoxical functions: the hashtag both enables
      the construction of a sexual identity within an affirming community and also
      reinforces the power relations that compel individuals to name and account for
      their sexual selves. By illustrating one way sexual identities function in the
      online lives of young women, this research complicates other scholars' findings
      that the salience of sexual identity categories is decreasing.

PMID- 29173133
TI  - The detection of Entamoeba histolytica and Toxoplasma gondii in wastewater.
AB  - To increase current knowledge on the epidemiology of protozoan parasites in
      wastewater treatment plants (WWTP), the occurrence of Entamoeba histolytica and
      Toxoplasma gondii in raw and treated wastewater was investigated. Samples were
      collected from WWTP twice a month over a period of 8 months. Determination of
      protozoa was performed using polymerase chain reaction (PCR) and light
      microscopy. After concentration and purification of wastewater samples, DNA
      extraction was conducted followed by PCR amplification of small subunit ribosomal
      RNA (SSU rRNA) gene sequences of E. histolytica and B1 gene of T. gondii. Loop
      Mediated Isothermal Amplification (LAMP) primer set was designed from E.
      histolytica hemolysin gene HLY6. Amplification of DNA in the LAMP mixture was
      monitored by naked eye as a blue color solution after addition of,
      hydroxynaphthol blue (HNB) to the reaction tube. Light microscopy revealed the
      presence of Entamoeba in all raw wastewater samples and treated water samples.
      PCR amplification of DNA products revealed that all, (9/9) wastewater samples
      were positive for Entamoeba. None was positive for Toxoplasma. These findings,
      which corroborate recent observations, indicate that E. histolytica may pose a
      public health risk.

PMID- 29173135
TI  - A 64-year-old woman with interstitial lung disease and positive antibodies
      against aminoacyl-transfer RNA synthetases in the absence of myositis:
      presentation of an anti-PL-12 positive antisynthetase syndrome.
AB  - Introduction The antisynthetase syndrome is a rare autoimmune disease described
      by the presence of inflammatory myositis, interstitial lung disease and
      antibodies against aminoacyl-transfer RNA synthetases. Interstitial lung disease
      can be the only manifestation in the absence of an inflammatory myositis. Other
      clinical signs are Raynaud phenomenon, hyperkeratotic skin lesions, fever and
      inflammatory polyarthritis. Case presentation We report the case of a 64-year old
      woman who complained of a dry cough, progressive dyspnea and arthralgia since 2
      years, with no other systemic symptoms. High resolution computed tomography
      (HRCT) of the thorax showed the presence of bilateral ground glass opacities,
      reticular opacities and some traction bronchiectasis. Further biochemical testing
      revealed the presence of anti-PL12 antibodies. Management The diagnosis of
      antisynthetase syndrome was made and the patient was treated with steroids and
      azathioprine with a good response. Conclusion The search for antisynthetase
      antibodies should always be considered in patients with an interstitial lung
      disease without any other clinical symptoms or signs of an underlying connective
      tissue disease.

PMID- 29173134
TI  - An age-structured within-host HIV-1 infection model with virus-to-cell and cell
      to-cell transmissions.
AB  - In this paper, a within-host HIV-1 infection model with virus-to-cell and direct
      cell-to-cell transmission and explicit age-since-infection structure for infected
      cells is investigated. It is shown that the model demonstrates a global threshold
      dynamics, fully described by the basic reproduction number. By analysing the
      corresponding characteristic equations, the local stability of an infection-free
      steady state and a chronic-infection steady state of the model is established. By
      using the persistence theory in infinite dimensional system, the uniform
      persistence of the system is established when the basic reproduction number is
      greater than unity. By means of suitable Lyapunov functionals and LaSalle's
      invariance principle, it is shown that if the basic reproduction number is less
      than unity, the infection-free steady state is globally asymptotically stable; if
      the basic reproduction number is greater than unity, the chronic-infection steady
      state is globally asymptotically stable. Numerical simulations are carried out to
      illustrate the feasibility of the theoretical results.

PMID- 29173136
TI  - Studies on Foam Decay Trend and Influence of Temperature Jump on Foam Stability
      in Sclerotherapy.
AB  - OBJECTIVES: This study investigated the influence of temperature jump and liquid
      gas ratio on foam stability to derive the foam-decay law. METHODS: The
      experimental group conditions were as follows: mutation temperatures (10 degrees
      C, 16 degrees C, 20 degrees C, 23 degrees C, 25 degrees C, and 27 degrees C to
      >37 degrees C) and liquid-gas ratios (1:1, 1:2, 1:3, and 1:4). The control group
      conditions were as follows: temperatures (10 degrees C, 16 degrees C, 20 degrees
      C, 23 degrees C, 25 degrees C and 27 degrees C) and liquid-gas ratios (1:1, 1:2,
      1:3, and 1:4). A homemade device manufactured using the Tessari DSS method was
      used to prepare the foam. The decay process was videotape recorded. In the
      drainage rate curve, the temperature rose, and the liquid-gas ratio varied from
      1:1 to 1:4, causing faster decay. RESULTS: In the entire process, the foam volume
      decreased with increasing drainage rate. The relationships were almost linear.
      Comparison of the experimental and control groups shows that the temperature jump
      results in a drainage time range of 1 to 15 seconds. The half-life ranges from 10
      to 30 seconds. The maximum rate is 18.85%. Changes in the preparation temperature
      yields a drainage time range of 3 to 30 seconds. The half-life varies from 20 to
      60 seconds. CONCLUSION: Decreasing the temperature jump range and liquid-gas
      ratio gradually enhances the foam stability. The foam decay time and drainage
      rate exhibit an exponential function distribution.

PMID- 29173137
TI  - Testing Hypotheses About Social Targets.
AB  - The information search process is a critical cognitive activity in many domains,
      such as in legal investigations and criminal judgments. Previous research focused
      on leading strategies, in particular on the use of open and matching questions.
      The present research aimed to explore the use of asymmetric questions, namely
      dichotomous queries for which the "yes" and "no" answers are not equally
      diagnostic, during social hypothesis testing. In Study 1 (N = 253) participants
      were asked to select questions to assess a social target on some moral and
      nonmoral attributes. Explicit instructions to avoid asymmetric strategies were
      introduced. In Study 2 (N = 98) participants were asked to play the role of a
      judge who is supposed to be impartial. Results showed that, although people
      spontaneously use asymmetric yes-no format questions during the information
      search on moral traits, in certain conditions the use of such strategies could be
      monitored. Practical implications of these findings are discussed.

PMID- 29173138
TI  - Are Emotions Abstract or Concrete?
AB  - The ability to identify and communicate emotions is essential to psychological
      well-being. Yet research focusing exclusively on emotion concepts has been
      limited. This study examined nouns that represent emotions (e.g., pleasure,
      guilt) in comparison to nouns that represent abstract (e.g., wisdom, failure) and
      concrete entities (e.g., flower, coffin). Twenty-five healthy participants
      completed a lexical decision task. Event-related potential (ERP) data showed that
      emotion nouns elicited less pronounced N400 than both abstract and concrete
      nouns. Further, N400 amplitude differences between emotion and concrete nouns
      were evident in both hemispheres, whereas the differences between emotion and
      abstract nouns had a left-lateralized distribution. These findings suggest
      representational distinctions, possibly in both verbal and imagery systems,
      between emotion concepts versus other concepts, implications of which for
      theories of affect representations and for research on affect disorders merit
      further investigation.

PMID- 29173139
TI  - Walking Back to the Future.
AB  - Embodied cognition frameworks suggest a direct link between sensorimotor
      experience and cognitive representations of concepts ( Shapiro, 2011 ). We
      examined whether this holds also true for concepts that cannot be directly
      perceived with the sensorimotor system (i.e., temporal concepts). To test this,
      participants learned object-space (Exp. 1) or object-time (Exp. 2) associations.
      Afterwards, participants were asked to assign the objects to their location in
      space/time meanwhile they walked backward, forward, or stood on a treadmill. We
      hypothesized that walking backward should facilitate the online processing of
      "behind"/"past"-related stimuli, but hinder the processing of "ahead"/"future"
      related stimuli, and a reversed effect for forward walking. Indeed, "ahead"- and
      "future"-related stimuli were processed slower during backward walking. During
      forward walking and standing, stimuli were processed equally fast. The results
      provide partial evidence for the activation of specific spatial and temporal
      concepts by whole-body movements and are discussed in the context of movement
      familiarity.

PMID- 29173140
TI  - The Mere Exposure Instruction Effect.
AB  - The mere exposure effect refers to the well-established finding that people
      evaluate a stimulus more positively after repeated exposure to that stimulus. We
      investigated whether a change in stimulus evaluation can occur also when
      participants are not repeatedly exposed to a stimulus, but are merely instructed
      that one stimulus will occur frequently and another stimulus will occur
      infrequently. We report seven experiments showing that (1) mere exposure
      instructions influence implicit stimulus evaluations as measured with an Implicit
      Association Test (IAT), personalized Implicit Association Test (pIAT), or Affect
      Misattribution Procedure (AMP), but not with an Evaluative Priming Task (EPT),
      (2) mere exposure instructions influence explicit evaluations, and (3) the
      instruction effect depends on participants' memory of which stimulus will be
      presented more frequently. We discuss how these findings inform us about the
      boundary conditions of mere exposure instruction effects, as well as the mental
      processes that underlie mere exposure and mere exposure instruction effects.

PMID- 29173141
TI  - Too Tasty to Be Ignored.
AB  - Recent research has shown that even non-salient stimuli (colored circles) can
      gain attentional weight, when they have been loaded with some value through
      previous reward learning. The present study examined such value-based attentional
      weighting with intrinsically rewarding food stimuli. Different snacks were
      assumed to have different values for people due to individual food preferences.
      Participants indicated their preferences toward various snacks and then performed
      a flanker task with these snacks: they had to categorize a target snack as either
      sweet or salty; irrelevant flanker snacks were either compatible or incompatible
      with the target category. Results of a linear mixed-effects model show that the
      effect of flanker compatibility on participants' performance (response times)
      increased with the participants' preference toward the flanking snacks. This
      shows, for the first time, that attentional weightings in a flanker task with
      naturalistic stimuli (snacks) are modulated by participants' preferences toward
      the flankers.

PMID- 29173142
TI  - Sequence analysis of the N-acetyltransferase 2 gene (NAT2) among Jordanian
      volunteers.
AB  - The present study aimed to identify the NAT2 haplotypes, linkage disequilibrium,
      and novel NAT2 genetic variants among Jordanian population. We isolated the
      genomic DNA from 68 healthy, Arab, unrelated Jordanian volunteers to amplify the
      protein-coding region of NAT2 gene by polymerase chain reaction (PCR). Then, the
      amplified PCR products were sequenced using Applied Biosystems Model (ABI3730x1).
      It is found that the allele frequencies of known NAT2 genetic variants 191G>A,
      282C>T, 341T>C, 481C>T, 590G>A, and 803A>G were 0.7, 26.5, 48.5, 35.3, 30.9, and
      32.4%, respectively. The NAT2 allele frequencies were generally similar to those
      of white Europeans but different from those of Asian and African populations. The
      most common NAT2 haplotype was NAT2*5B with a frequency of 29.3%. According to
      the NAT2 haplotype frequencies, 72% (95% confidence interval 61.4-82.7%) of the
      volunteers were slow encoding NAT2 haplotype acetylators. The NAT2*5 represented
      variants 341T>C and 481C>T were in strong but not complete linkage disequilibrium
      (D' = 0.8, r2 = 0.63). In addition, this study found a novel nonsynonymous NAT2
      436G>A genetic variant with low frequency (0.7%). However, this novel variant was
      predicted to be tolerated and not harmful to the NAT2 protein, using in silico
      prediction tools. It is concluded that the frequency of slow encoding NAT2
      haplotype was high among Jordanian volunteers, which may have effects on drug
      responses and susceptibility to some diseases, such as cancers.

PMID- 29173143
TI  - The Role of Grb2 in Cancer and Peptides as Grb2 Antagonists.
AB  - BACKGROUND: Growth factor receptor-bound protein 2 (Grb2) is a 25 kDa adaptor
      protein, which was originally discovered to accomplish basic cellular events such
      as cell growth, cell proliferation, and metabolism. However, recent studies
      evidenced that Grb2 was largely involved in multiple tumor malignancies. The
      mature Grb2 is a 217 amino acid sequence, which consists of one Src homology 2
      (SH2) domain flanked by two Src homology 3 (SH3) domains. Using these binding
      motives, the ubiquitously expressed Grb2 acts as an intermediate between cell
      surface activated receptors and downstream targets. OBJECTIVES: Consequently, the
      Grb2 becomes the key element of this oncogenesis and launched a number of
      defected signaling cascades. Therefore, vast concern of the Grb2 in multiple
      cancer patterns makes it an attractive therapeutic target. In this review, we
      have compiled the maximum tumor conformations caused by the involvement of the
      Grb2, the central role of Grb2 in numerous oncogenic pathways and particular
      approaches that can be useful to downregulate the Grb2 overexpression. We will
      discuss in details the activity of different types of novel peptides, their high
      affinity for the Grb2 protein and blockade of Grb2 mediated signaling pathways by
      targeting the SH2/SH3 binding sites. METHODS & RESULTS: There is a three-fold
      aspect to this review: Grb2 protein introduction, Grb2 protein involvement in
      cancer, and the role of peptides as Grb2 antagonists. First, Grb2 and compiled
      maximum tumor conformations induced by Grb2 involvement were introduced.
      Secondly, several oncogenic pathways of Grb2 involvement and particular
      approaches potentially useful to downregulate Grb2 overexpression were outlined.
      The activity of different types of novel peptides for the Grb2 protein was also
      detailed. Last but not least, the blockade of Grb2-mediated signaling pathways by
      targeting SH2/SH3 binding sites were summarized. CONCLUSION: We have epitomized
      the utmost cancer malignancies caused by abnormal signaling of the Grb2 adaptor
      molecule. Indeed, Grb2's enormous involvement in the progression and development
      of different cancers broaden our tactics to build anticancer drug candidates.
      Depending on the high affinity and increased specificity we have described the
      major potent peptides which may efficiently target and block the SH2 or SH3 arms
      of the Grb2. It may be of benefit for developing novel anticancer peptides.
      However, further work is needed to pinpoint more binding motives of Grb2 to
      generate efficacious anticancer agents for diverse human cancers in the near
      future.

PMID- 29173144
TI  - Editorial: The Care of Hospitalized Children.

PMID- 29173145
TI  - Histamine H3 Receptor Ligands in the Group of (Homo)piperazine Derivatives.
AB  - Since its discovery in 1983, followed by gene cloning in 1999, the histamine H3
      receptor served as an outstanding target for drug discovery. The wide spectrum of
      possible therapeutic implications makes H3R's one of the most researched areas in
      the vast GPCR ligands field - started from imidazole containing ligands, through
      various successful imidazole replacements, with recent introduction of Wakix(r)
      to pharmaceutical market. One such replacement is piperazine moiety, a
      significant versatile scaffold in rational drug design for most of the GPCR
      ligands. Therefore, herein, we review ligands built on piperazine, as well as its
      seven membered analogue azepine, that target H3R's and their potential
      therapeutical applications, in order to elucidate the current state of the art in
      this vast field. Due to a high level of structural divergence among compounds
      described herein, we decided to divide them into groups, where the key division
      element was the position of nitrogen basicity decreasing moieties in
      (homo)piperazine ring. Paying attention to a number of published structures and
      their overall high biological activity, one can realize that the (homo)piperazine
      scaffold bids a versatile template also for histamine H3 receptor ligands. With
      two possible substitution sites and therefore a number of possible structural
      combinations, piperazine derivatives stand as one of the largest group of high
      importance among H3R ligands.

PMID- 29173146
TI  - Recent Advances in Peptide-Based Approaches for Cancer Treatment.
AB  - Peptide-based pharmaceuticals have recently experienced a renaissance due to
      their ability to fill the gap between the two main classes of available drugs,
      small molecules and biologics. Peptides combine the high potency and selectivity
      typical of large proteins with some of the characteristic advantages of small
      molecules such as synthetic accessibility, stability and the potential of oral
      bioavailability. One of the applications in which peptide-based approaches have
      grown rapidly is cancer therapy, with a focus on new and established targets.
      Many novel peptide-based methods for cancer treatment have been developed in the
      last few years, ranging from naturally-occurring and modified peptides to peptide
      drug conjugates, peptide nanomaterials and peptide-based vaccines. This review
      focuses on recent advances, advantages and challenges of these selected peptide
      based approaches for cancer treatment.

PMID- 29173147
TI  - Recent Developments of 18F-FET PET in Neuro-oncology.
AB  - BACKGROUND: From the past decade to date, several studies related to O-(2-
      [18F]fluoroethyl)-L-tyrosine (18F-FET) positron emission tomography (PET) in
      brain tumours have been published in the literature. OBJECTIVE: The aim of this
      narrative review is to summarize the recent developments and the current role of
      18F-FET PET in brain tumours according to recent literature data. METHODS: Main
      findings from selected recently published and relevant articles on the role of
      18F-FET PET in neuro-oncology are described. RESULTS: 18F-FET PET may be useful
      in the differential diagnosis between brain tumours and non-neoplastic lesions
      and between low-grade and high-grade gliomas. Integration of 18F-FET PET into
      surgical planning allows better delineation of the extent of resection beyond
      margins visible with standard MRI. For biopsy planning, 18F-FET PET is
      particularly useful in identifying malignant foci within non-contrast-enhancing
      gliomas. 18F-FET PET may improve the radiation therapy planning in patients with
      gliomas. This metabolic imaging method may be useful to evaluate treatment
      response in patients with gliomas and it improves the differential diagnosis
      between brain tumours recurrence and posttreatment changes. 18F-FET PET may
      provide useful prognostic information in high-grade gliomas. CONCLUSION: Based on
      recent literature data 18F-FET PET may provide additional diagnostic information
      compared to standard MRI in neuro-oncology.

PMID- 29173148
TI  - Trends and Prospects of Plant Proteases in Therapeutics.
AB  - The main function of proteases in any living organism is the cleavage of proteins
      resulting in the degradation of damaged, misfolded and potentially harmful
      proteins and therefore providing the cell with amino acids essential for the
      synthesis of new proteins. Besides this main function, proteases may play an
      important role as signal molecules and participate in numerous protein cascades
      to maintain the vital processes of an organism. Plant proteases are no exception
      to this rule. Moreover, in contrast to human-encoded enzymes, many plant
      proteases possess exceptional features such as higher stability, unique substrate
      specificity and a wide pH range for enzymatic activity. These valuable features
      make plant-derived proteolytic enzymes suitable for many biomedical applications,
      and furthermore, the plants can serve as factories for protein production. Plant
      proteases are already applied in the treatment of several pathological conditions
      in the human organism. Some of the enzymes possess antitumour, antibacterial and
      antifungal activity. The collagenolytic activity of plant proteases determines
      important medical applications such as the healing of wounds and burn
      debridement. Plant proteases may affect blood coagulation processes and can be
      applied in the treatment of digestive disorders. The present review summarizes
      recent advances and possible applications for plant proteases in biomedicine, and
      proposes the further development of plant-derived proteolytic enzymes in the
      biotechnology and pharmaceutical industries.

PMID- 29173149
TI  - Current Challenges and Future of Lipid nanoparticles formulations for topical
      drug application to oral mucosa, skin, and eye.
AB  - BACKGROUND: Topical drug administration offers an attractive route with minimal
      invasiveness. It also avoids limitations of intravenous administration such as
      the first pass metabolism and presystemic elimination within the gastrointestinal
      tract. Furthermore, topical drug administration is safe, have few side effects,
      is easy to apply, and offers a fast onset of action. However, the development of
      effective topical formulations still represents a challenge for the desired
      effect to be reached, locally or systemically. Solid lipid nanoparticles and
      nanostructured lipid carriers are particular candidates to overcome the problem
      of topical drug administration. The nanometric particle size of lipid
      nanoparticles favors the physical adhesion to the skin or mucosal, what can also
      be attained with the formation of hybrid (nanoparticles/polymer) systems.
      METHODS: In this review, we discuss the major challenges for lipid nanoparticles
      formulations for topical application to oral mucosa, skin, and eye, highlighting
      the strategies to improve the performance of lipid nanoparticles for topical
      applications. Next, we critically analyzed the in vitro and in vivo approaches
      used to evaluate lipid nanoparticles performance and toxicity. CONCLUSION: We
      addressed some major drawbacks related to lipid nanoparticle topical formulations
      and concluded the key points that have to be overcome to help them to reach the
      market in topical formulations to oral mucosa, skin and eye.

PMID- 29173150
TI  - An Update of Patents, Preclinical and Clinical Outcomes of Lipid Nanoparticulate
      Systems.
AB  - BACKGROUND: Lipid nanoparticles have attracted increased degree of scientific and
      commercial attention in the last decade. The lipidic nanoparticles have emerged
      as a potential alternative to other nano-scale systems due to their various
      advantages over them and also due to overcoming the shortcomings of the already
      available colloidal systems like liposomes, niosomes and polymeric nanoparticles.
      DESCRIPTION: These have been investigated for delivery of macromolecules, genes,
      siRNA and other therapeutic agents for oral, topical, parenteral administration
      and target site specific delivery for various diseases like cancer, ocular
      diseases and brain disorders. The lipid nanoparticles have evolved from SLNs,
      then NLCs and lipid drug conjugates overcoming any issues related to production
      and formulation and adding advantages, if any. The current review article focuses
      on the lipid nanoparticles, their formulation approaches and current advancements
      in the field through recent clinical trials and patents. This manuscript embodies
      various patents, preclinical and clinical aspects related to the lipidic
      nanocarriers. CONCLUSION: Over the years the lipidic nanoparticulate systems have
      evolved as significant carriers for improved therapeutics and in diagnostic
      field. The large number of patents and preclinical trials in the recent years
      suggests that these systems will find immense potential in near future.

PMID- 29173151
TI  - Lipid Based Nanoparticles as Inherent Reversing Agents of Multidrug Resistance in
      Cancer.
AB  - BACKGROUND: Multidrug resistance in cancer is the ability of a cancer cell to
      resist treatment with a wide range of structurally and functionally dissimilar
      chemotherapeutics. The resistant phenotype could arise in response to several
      cellular changes that ultimately result in a decrease in intracellular drug
      accumulation (or effectiveness), either by limiting cellular drug entry, or by
      expulsion of those molecules that have made it into the cell. Both blocking drug
      cellular entry and its expulsion are mostly brought about by the cell membrane.
      Several pharmaceutical excipients (mainly lipids, surfactants and amphililc
      copolymers) have been reported to reverse multidrug resistance by addressing cell
      membrane related changes resulting in low intracellular drug levels in resistant
      cells. These excipients are routinely used in the preparation of lipid based
      nanoparticles endowing inherent multidrug resistance reversing properties to
      these nanoparticles. METHODS: In this review, cell membrane alterations resulting
      in multidrug resistance will be initially reviewed, followed by a discussion of
      the different types of lipid NPs and the potential held by the excipients used in
      their preparation in multidrug resistance reversal. Finally, a discussion on how
      lipid nanoparticles have been engineered and used in different occasions to
      enable multidrug resistance reversal is included. CONCLUSION: The superior role
      held by lipid nanoparticles in comparison to free excipients will be highlighted.

PMID- 29173152
TI  - Lipid-based Nanosized Delivery Systems for Fluoroquinolones: a Review.
AB  - BACKGROUND: The class of fluoroquinolone antibiotics, due to its core chemical
      modifications, is considered as wide-spectrum antibacterial drugs with useful
      pharmacokinetic and pharmacodynamic properties. However, because of their poor
      solubility in water, they are used as salts (lactates or hydrochlorides).
      Fluoroquinolones, bacterial membranes and eukaryotic cell membranes interactions
      are well known and their permeation properties are well investigated. In fact,
      they are concentrated inside the cells and intracellular compartments.
      Nanotechnology in Drug Delivery has developed many supra-molecular structures
      that have been used to improve both pharmacokinetic and pharmacodynamic
      properties. The main results of the published papers showed reduction of
      toxicity, higher intracellular concentrations (both bacteria and eukaryotic),
      enhancement of antimicrobial activity, prolonged drug release, decreased
      mortality in animal model studies, improved water solubility and improved in
      vitro efficacy against intracellular pathogens. METHODS: a literature search was
      performed in the NCBI-PUBMED database, with no time range, using the keywords
      "solid lipid nanoparticles" and 'quinolones' or the name of single antibiotics.
      RESULTS: the most important aspects of lipid-based nanocarrier technology used
      for fluoroquinolones have been highlighted, with a focus on the latest
      formulation developments that have led to significant improvements of
      pharmacokinetics and pharmacodynamics. Both technological and microbiological
      aspects of published papers have been discussed. CONCLUSION: the potentiality of
      using lipid nanoparticles to improve the efficacy and potency of quinolone
      antibiotics has been supported by recent scientific publications, although some
      criticism appeared due to the microbiological investigative methods used and
      because of lack of systematic evaluation about the influence of technological
      approaches to the in vitro and in vivo drug activity.

PMID- 29173153
TI  - Therapeutic potential of drug delivery by means of lipid nanoparticles: reality
      or illusion?
AB  - BACKGROUND: Solid lipid nanoparticles (SLN) are colloidal drug carrier systems
      that contribute several properties required from a sophisticated drug delivery
      system for increasing drug bioavailability and providing effective therapy. Many
      advantages of SLN have been reported over traditional dosage forms and their
      colloidal counterparts in the studies since the early 1990s. They were optimized
      for oral drug delivery for the first time. The first SLN formulations were
      produced by reducing the particle size of solid lipid microparticles by spray
      congealing technique in the late 1980s. Then, studies have been continued
      investigating for their different administration routes else including
      parenteral, transdermal, ocular, nasal, respiratory etc. METHODS: Their foremost
      qualifications such as their biocompatible nature and high drug entrapment
      efficiency make them promising colloidal drug carrier systems for the effective
      treatment of serious disasters like genetic disorders and cancer. CONCLUSION: In
      this review, therapeutic potential of drug delivery of SLN and nanostructured
      lipid carriers (NLC, the second generation of SLN) are summarized considering
      researches and patents on their administration via different routes and their
      preparations in the pharmaceutical market.

PMID- 29173154
TI  - Effective Delivery Routes And Strategies For Solid Lipid Nanoparticles (Sln) And
      Nanostructured Lipid Carriers (Nlc).
AB  - BACKGROUND: SLNs and NLCs have remarkably wide range of properties which make
      them useful for several potential applications in drug delivery, clinical
      medicine, and research, as well as in parenteral, dermal, pulmonary and topical
      delivery of drugs. The unique size-dependent properties of the solid lipid
      nanoparticles make them at the forefront of the rapidly developing field of
      nanotechnology offering development of new therapeutics having reduced toxic side
      effects and increased treatment efficacy. METHODS: SLNs and NLCs are very
      attractive drug delivery candidates, primarily due to their relatively stable
      constituents and probable ease of drug encapsulations. The incorporation of drugs
      into nanocarriers like SLNs and NLCs for several levels of drug targeting offers
      good potential in gene transfer, cosmetic and food industry with great promise
      for reaching the goal of controlled and site-specific drug delivery. Lipid
      nanoparticle drug delivery technology presents considerable opportunities for
      improving medical therapeutics, but the technology's potential remains
      unrealized. RESULTS: The review has focused on the various effective delivery
      routes and strategies for SLNs and NLCs, and their applicability in the
      encapsulation of therapeutics. Number of research works has been successfully
      carried out in this area. It would result in a simultaneous improvement in the
      quality, efficacy, and safety profile of drugs. CONCLUSION: However, because of
      mentioned limitations and difficulties related to them, the total number of
      products on the market is still limited. Although the concept of PEGylation to
      increase half-life of nanoparticles revolutionized the nanoparticle-mediated drug
      delivery field, significant improvements are warranted in this area.

PMID- 29173155
TI  - Imaging of Bacteria: Is there Any Hope for the Future Based on Past Experience?
AB  - Infectious diseases remain a major health problem and cause of death worldwide.
      It is expected that the socio-economic impact will further intensify due to
      escalating resistance to antibiotics, an ageing population and an increase in the
      number of patients under immunosuppressive therapy and implanted medical devices.
      Even though radiolabeled probes and leukocytes are routinely used in clinical
      practice, it might still be difficult to distinguish sterile inflammation from
      inflammation caused by bacteria. Moreover, the majority of these probes are based
      on the attraction of leukocytes which may be hampered in neutropenic patients.
      Novel approaches that can be implemented in clinical practice and allow for swift
      diagnosis of infection by targeting the microorganism directly, are posing an
      attractive strategy. Here we review the current strategies to directly image
      bacteria using radionuclides and we provide an overview of the preclinical
      efforts to develop and validate new approaches. Indeed, significant progress has
      been made in the past years, but very few radiopharmaceuticals (that were
      promising in preclinical studies) have made it into clinical practice. We will
      discuss the challenges that remain to select good candidates for imaging agents
      targeting bacteria.

PMID- 29173156
TI  - Identification of Human Acetylcholinesterase Inhibitors from the Constituents of
      EGb761 by Modeling Docking and Molecular Dynamics Simulations.
AB  - AIM AND OBJECTIVE: EGb761, a standardized and well-defined product extract of
      Ginkgo biloba leaves, has beneficial role in the treatment of multiple diseases,
      particularly Alzheimer's disease (AD). Identification of natural
      acetylcholinesterase (AChE) inhibitors from EGb761 would provide a novel
      therapeutic approach against the Alzheimer's disease. MATERIAL AND METHOD: A
      series of 21 kinds of promising EGb761 compounds were selected, and subsequently
      evaluated for their potential ability to bind AChE enzyme by molecular docking
      and a deep analysis of protein surface pocket features. RESULTS: Docking results
      indicated that these compounds can bind tightly with the active site of human
      AChE, with favorable distinct interactions around several important residues
      Asp74, Leu289, Phe295, Ser293, Tyr341, Trp286 and Val294 in the active pocket.
      Most EGB761 compounds could form the hydrogen bond interactions with the
      negatively charged Asp74 and Phe295 residues. Among these compounds, diosmetin is
      the one with the best-predicted docking score while three key hydrogen bonds can
      be formed between small molecule and corresponding residues of the binding site.
      Besides, other three compounds luteolin, apigenin, and isorhamnetin have better
      predicted docking scores towards AChE than other serine proteases, i.e. Elastase,
      Tryptase, Factor XA, exhibiting specificity for AChE inhibition. The RMSD and MM
      GBSA results from molecular dymamic simulations indicated that the docking pose
      of diosmetin-AChE complex displayed highly stable, which can be used for
      validating the accuracy of molecular docking study. Subsequently, the AChE
      inhibitory activities of these compounds were evaluated by the Ellman's
      colorimetric method. CONCLUSION: The obtained results revealed that all the four
      compounds exhibited modest AChE inhibitory activity, among which Diosmetin
      manifested remarkable anti-AChE activity, comparable with the reference compound,
      Physostigmine. It can be deduced that these EGB761 compounds can be regarded as a
      promising starting point for developing AChE inhibitors against AD.

PMID- 29173157
TI  - In vitro Characterization of NPS Metabolites Produced by Human Liver Microsomes
      and the HepaRG Cell Line Using Liquid Chromatographyhigh Resolution Mass
      Spectrometry (LC-HRMS) Analysis: Application to Furanyl Fentanyl.
AB  - BACKGROUND: Identification of metabolites is of importance in the challenge of
      new psychoactive substances (NPS) as it could improve the detection window in
      biological matrices in clinical and forensic cases of intoxication. Considering
      the numerous and diverse NPS reported each year, producers increasingly appear
      today to be targeting non-controlled synthetic opioids, involving fentanyl
      derivatives such as furanyl fentanyl (Fu-F). OBJECTIVE: This work aims to
      investigate and compare metabolites of Fu-F using two in vitro experimental
      approaches. METHODS: CYP- and UGT-dependent metabolites of Fu-F were investigated
      by means of analyses of both human liver microsome (HLM) and hepatic (HepaRG)
      cell line incubates using liquid chromatography with high-resolution mass
      detection and, subsequently, compared and confronted to recently published data.
      RESULTS: Seventeen Fu-F metabolites were produced and several metabolic pathways
      can be postulated. HLMs and HepaRG cultures appear to be complementary: HepaRG
      cells produced 9 additional metabolites, but which appear to be minor in vivo
      metabolites. Specific* and/or abundant Fu-F metabolites are dihydrodiol-Fu-F*,
      norFu-F* and despropionylfentanyl. However, norFu-F seems to be inconstantly
      observed in in vivo cases. Furthermore, a sulfate metabolite presents at
      significant rate in urine obtained from FU-F users was not identified here, as in
      another in vitro study. CONCLUSION: HLMs represent an acceptable first choice
      tool for a single NPS metabolism study in forensic laboratories. Dihydrodiol-Fu-F
      and despropionylfentanyl could be proposed as reliable metabolites to be recorded
      in HRMS libraries in order to improve detection of Fu-F users. Nevertheless,
      additional verifications of in vivo data remain necessary to confirm relevant
      blood and urinary metabolites of Fu-F.

PMID- 29173158
TI  - Novel Insights into the Molecular Interaction of a Panduratin A Derivative with
      the Non Structural Protein (NS3) of Dengue Serotypes: A Molecular Dynamics Study.
AB  - BACKGROUND: The ligand PKP10 having substitution of Cl- at R2 and R3 positions of
      ring A of Panduratin A i.e., ((1R,2S,5S)-5-(2,3-dichlorophenyl)-3-methyl-2-(3
      methylbut-2-nyl)cyclohex-3- enyl)(2,6-dihydroxy-4-methylphenyl)methanone hydrate)
      has been observed to block the Nuclear Receptor Binding Protein binding site of
      Non Structural protein 3 in all dengue serotypes. In continuation with our
      earlier study, we have reported sixty novel Panduratin A derivatives compounds
      where substitution was done in positions 2 and 3 position of the benzyl ring A of
      Panduratin A with various substituents. METHODS: We selected ((1R,2S,5S)-5-(2,3
      dichlorophenyl)-3-methyl-2-(3-methylbut-2-nyl)cyclohex-3- nyl) (2,6-dihydroxy-4
      methylphenyl) methanone hydrate) (PKP10) for molecular dynamics (MD) simulations
      as it constantly produced lowest CDocker interaction energy of among all the
      sixty five derivatives. The CDocker interaction energy was predicted to be 
      140.804, -79.807, -78.217 and -84.073 Kcalmol-1 respectively against NS3 protein
      of dengue serotypes (DENV1-4). To understand the dynamics of the PKP10 with NS3
      protein, each complex was subjected to molecular dynamics simulations of 50 ns in
      aqueous solution. MD (Molecular Dynamics) simulation study revealed that the
      binding of ligand PKP10 at the active site of NS3 induces a conformational change
      in all serotypes which was well supported by principal component analysis.
      RESULT: To the best of our knowledge, this is first ever study which provided
      atomistic insights into the interaction of PKP10 with NS3 protein of dengue
      serotypes. CONCLUSION: The result from our study along with in vitro studies is
      expected to open up better avenues to develop inhibitors for dengue virus in the
      near future.

PMID- 29173159
TI  - Antioxidant Potential and Wound Healing Activity of Biosurfactant Produced by
      Acinetobacter junii B6.
AB  - BACKGROUND: Recently, the development of a safe bioactive material with
      antioxidant properties, which can improve healing activity are focusing.
      Biosurfactants are very famous for their antimicrobial and free radical
      scavenging activities. Thereof, the main aim of the present study was to
      investigate the antioxidant and wound healing activity of the lipopeptide
      biosurfactant (LBS) produced by Acinetobacter junii B6. DPPH radical scavenging
      activities and FRAP assays were used to measure the antioxidant properties.
      METHODS: For evaluation of the wound healing activity, 36 rats (previously
      wounded in depilated thoracic region) were randomly distributed into six groups
      and chromatic, wound contraction, and histopathological feature were examined.
      The assessment levels of reactive oxygen species (ROS) after LBS exposure were
      determined using malondialdehyde (MDA), hydrogen peroxide (H2O2), and glutathione
      (GSH) assay kits. RESULTS: DPPH assay showed notable scavenging activities at the
      corresponding concentrations with IC50 value of 0.7 mg/ml. The reductive potency
      of the LBS showed lower performance at low concentration, while exhibited a
      remarkable increase at higher concentration. The best histopathological remission
      was achieved following treatment by 5 mg/ml of the LBS. Scar wounds at day 13
      showed the lowest lesion sizes, increased re-epithelialization, hair follicle
      detection, and decreased amounts of neutrophilic inflammation, immaturity of the
      wound bed, erythema, edema, capillary, and retention of necrotic tissue.
      CONCLUSION: Results from MDA, H2O2, and GSH levels of the treated sample
      confirmed the scavenging property of the bacterial derived LBS through ROS. It
      could be concluded that the pharmaceutical formula encourages the wound healing
      because of its notable antioxidant capacity. HIGHLIGHTS: * DPPH and FRAP assays
      showed notable scavenging activity. * MDA, H2O2, and GSH; confirmed the
      scavenging property of the derived biosurfactant through ROS. * Synthesized
      formula encourages the healing of the wound because of its antioxidant capacity.

PMID- 29173160
TI  - Simple and Fast Gas-chromatography Mass Spectrometry Assay to Assess Delta 9
      Tetrahydrocannabinol and Cannabidiol in Dogs Treated with Medical Cannabis for
      Canine Epilepsy.
AB  - BACKGROUND: To date, an increasing number of pet owners, especially in the USA,
      are using cannabis-derived products containing generally delta 9
      tetrahydrocannabinol (THC) and cannabidiol (CBD) to help their animals' health.
      Unfortunately, studies on the clinical use of cannabinoids in veterinary medicine
      are still limited, and the application of analytical methodologies for the
      determination of cannabinoids in animal (especially dog) biological matrices such
      as plasma, is still missing. METHODS: A reliable, fast, accurate, simple gas
      chromatography-mass spectrometry (GC-MS) method was developed and validated for
      the quantification of THC and CBD in plasma samples of eight dogs under
      therapeutic treatment for epilepsy and receiving oral administration of medical
      cannabis (Bediol). RESULTS: The method was linear for both the analytes under
      investigation with coefficients of determination (r2) of at least 0.99. Absolute
      analytical recovery (mean +/- SD) ranged from 80.6 +/- 6.2% for THC and 81.7 +/-
      4.3% for CBD. The matrix effect showed less than 10% analytical suppression due
      to endogenous substances for both the analytes. The intra-assay and inter-assay
      precision values ranged from 4.9% to 12.7%, and from 5.2% to 8.7% respectively.
      The intra-assay and inter-assay accuracy values ranged from 2.3% to 9.6% and from
      3.4% to 13.0%, respectively. CONCLUSION: The validated method was successfully
      applied to real samples; moreover, to assess the potential of the method
      applicability and robustness in future veterinary clinical studies on
      cannabinoids therapy, we attempted to follow the kinetic of THC and CBD in the
      plasma of two dogs under therapy at different times after Bediol administration.

PMID- 29173161
TI  - Analytical Strategies to Disclose Repeated Consumption of New Psychoactive
      Substances by Hair Analysis.
AB  - BACKGROUND: New psychoactive substances (NPS) are a heterogenic group of
      substances with different chemical structures and psychotropic effects. METHOD:
      Many pharmacotoxicological laboratories performing drug testing in conventional
      and nonconventional biological matrices for clinical and forensic purposes do not
      include screening procedures for NPS in their routine protocols. This is mainly
      due to the continued entry in the market of newly synthesized products, the low
      availability of reference standards, in particular of their metabolites, the low
      availability of immunochemical kits, etc. Moreover, many of the new compounds are
      very potent, and low doses ingested will lead to low concentrations in biological
      matrices, especially in hair. RESULTS: Hair analysis has become a powerful tool
      for detecting chronic drug use and has become a routine technique in forensic
      toxicology laboratories. CONCLUSION: The aim of this study was to set up
      analytical strategies to identify repeated consumption of NPS by hair analysis.
      Although UHPLC-MS/MS may represent the elective technique in studying NPS, a
      combination of both GC-MS and UHPLC-MS/MS techniques is useful in creating a
      complete toxicological image.

PMID- 29173163
TI  - Tocopherol and Tocotrienol: Therapeutic Potential in Animal Models of Stress.
AB  - BACKGROUND: Scientific reports had shown that stress is related to numerous
      pathological changes in the body. These pathological changes can bring about
      numerous diseases and can significantly cause negative effects in an individual.
      These include gastric ulcer, liver pathology and neurobehavioral changes. A
      common pathogenesis in many diseases related to stress involves oxidative damage.
      Therefore, the administration of antioxidants such as vitamin E is a reasonable
      therapeutic approach. However, there is conflicting evidence about antioxidant
      supplementation. OBJECTIVE: The aim of this work was to summarize documented
      reports on the effects of tocopherol and tocotrienol on various pathological
      changes induced by stress. RESULTS AND CONCLUSION: This review will reveal the
      scientific evidence of enteral supplementation of vitamin E in the forms of
      tocotrienol and tocopherol in animal models of stress. These models mimic the
      stress endured by critically ill patients in a clinical setting and psychological
      stress in individuals. Positive outcomes from enteral feeding of vitamin E in
      reducing the occurrence of stress-induced pathological changes are discussed in
      this review. These positive findings include their ability to reduced stress
      induced gastric ulcers, elevated liver enzymes and improved locomotors activity.
      Evidences showing tocotrienol and tocopherol effects are not just related to its
      ability to reduce oxidative stress but also acting on other mechanism, are
      discussed.

PMID- 29173162
TI  - Oral Fluid vs. Urine Analysis to Monitor Synthetic Cannabinoids and Classic Drugs
      Recent Exposure.
AB  - BACKGROUND: Urine is a common biological sample to monitor recent drug exposure,
      and oral fluid is an alternative matrix of increasing interest in clinical and
      forensic toxicology. Limited data are available about oral fluid vs. urine drug
      disposition, especially for synthetic cannabinoids. OBJECTIVE: To compare urine
      and oral fluid as biological matrices to monitor recent drug exposure among HIV
      infected homeless individuals. METHODS: Seventy matched urine and oral fluid
      samples were collected from 13 participants. Cannabis, amphetamines,
      benzodiazepines, cocaine and opiates were analyzed in urine by the enzyme
      multipliedimmunoassay- technique and in oral fluid by liquid chromatography
      tandem mass spectrometry (LCMSMS). Eleven synthetic cannabinoids were analyzed in
      urine and in oral fluid by LC-MSMS. RESULTS: Five oral fluid samples were
      positive for AB-FUBINACA. In urine, 4 samples tested positive for synthetic
      cannabinoids PB-22, 5-Fluoro-PB-22, AB-FUBINACA, and metabolites UR-144 5
      pentanoic acid and UR-144 4-hydroxypentyl. In only one case, oral fluid and urine
      results matched, both specimens being AB-FUBINACA positive. For cannabis, 40
      samples tested positive in urine and 30 in oral fluid (85.7% match). For cocaine,
      37 urine and 52 oral fluid samples were positive (75.7% match). Twenty-four urine
      samples were positive for opiates, and 25 in oral fluid (81.4% match). For
      benzodiazepines, 23 samples were positive in urine and 25 in oral fluid (85.7%
      match). CONCLUSION/DISCUSSION: These results offer new information about drugs
      disposition between urine and oral fluid. Oral fluid is a good alternative matrix
      to urine for monitoring cannabis, cocaine, opiates and benzodiazepines recent
      use; however, synthetic cannabinoids showed mixed results.

PMID- 29173164
TI  - Epigenetic Mechanisms: Role in Hematopoietic Stem Cell Lineage Commitment and
      Differentiation.
AB  - Major breakthroughs in the last several decades have contributed to our knowledge
      of the genetic regulation in development. Although epigenetics is not a new
      concept, unfortunately, the role of epigenetics has not come to fruition in the
      past. But the field of epigenetics has exploded within the past decade. Now,
      growing evidences show a complex network of epigenetic regulation in development.
      The epigenetic makeup of a cell, tissue or individual is much more complex than
      their genetic complement. Epigenetic modifications are more important for normal
      development by maintaining the gene expression pattern in tissue- and context
      specific manner. Deregulation of epigenetic mechanism can lead to altered gene
      expression and its function, which result in altered tissue specific function of
      cells and malignant transformation. Epigenetic modifications directly shape
      Hematopoietic Stem Cell (HSC) developmental cascades, including their maintenance
      of self-renewal and multilineage potential, lineage commitment, and aging. Hence,
      there is a growing admiration for epigenetic players and their regulatory
      function in haematopoiesis. Epigenetic mechanisms underlying these modifications
      in mammalian genome are still not completely understood. This review mainly
      explains 3 key epigenetics mechanisms including DNA methylation, histone
      modifications and non-coding RNAs inference in hematopoietic lineage commitment
      and differentiation.

PMID- 29173165
TI  - Exploring Promising Immunomodulatory Potential of Natural and Synthetic 1,3
      Diphenyl-2-propen-1-one Analogs: A Review of Mechanistic Insight.
AB  - The immune system is an intricate and coordinated nexus serving as a natural
      defense to preclude internal and external pathogenic insults. The deregulation in
      the natural balance of immunological functions as a consequence of either over
      expression or under expression of immune cells tends to cause disruption of
      homeostasis in the body and may lead to development of numerous immune system
      disorders. Chalcone moieties (1,3-diphenyl-2-propen-1-one) have been well
      documented as ideal lead compounds or precursors to design a wide range of
      pharmacologically active agents to down-regulate various immune disorders. Owing
      to their unique structural and molecular framework, these alpha, beta-unsaturated
      carbonyl-based moieties have also gained remarkable recognition due to their
      other multifarious pharmacological properties including antifungal, anti
      inflammatory, anti-malarial, antibacterial, anti-tuberculosis, and anticancer
      potential. Though a great number of methodologies are currently being employed
      for their synthesis, this review mainly focuses on the natural and synthetic
      chalcone derivatives that are exclusively synthesized via Claisen-Schmidt
      condensation reaction and their immunomodulatory prospects. We have critically
      reviewed the literature and provided convincing evidence for the promising
      efficacy of chalcone derivatives to modulate functioning of various innate and
      adaptive immune players including granulocytes, mast cells, monocytes,
      macrophages, platelets, dendritic cells, natural killer cells, and T-lymphocytes.

PMID- 29173166
TI  - Anticancer Potential of Thiazole Derivatives: A Retrospective Review.
AB  - This review brings forth the potential of thiazole derivatives for their
      anticancer activities. The emphasis is placed on the structural diversity of
      thiazole derivatives, responsible for their specific anticancer activity.
      Multiple classes of thiazole derivatives such as Schiff base, mono-, di-, tri-,
      and heterocyclic substituents that possess anticancer activity have been
      exemplified. Molecular modelling of compounds that predicts enhanced anticancer
      activity of the modified structures has also been elaborated in the review.
      Significant advancements in synthetic chemistry related to cytotoxicity can now
      better position the drug discovery team to undertake thiazoles as valuable leads.
      The beneficial thiazole derivatives possessing anticancer activity will reignite
      the interest of medicinal chemists in thiazole and their derivatives.

PMID- 29173168
TI  - CRISPR/Cas9 Editing to Facilitate and Expand Drug Discovery.
AB  - INTRODUCTION: The ability of most laboratories to easily access CRISPR/Cas9
      engineering tools has caused a revolution in biology. One of the areas that will
      continue to be impacted by genome editing is the drug discovery process.
      OBJECTIVE: CRISPR/Cas9 will not only serve to accelerate the drug discovery
      pipeline, but also streamline line it by identifying high-value targets,
      facilitating the validation of drug: target interactions and mechanisms of
      action, and stimulating the development of phenotype-based high throughput
      screens as alternatives to target-based assays. CONCLUSION: We review the
      literature and hurdles that have been overcome to develop the current generation
      of tools being used to enrich the drug discovery paradigm.

PMID- 29173167
TI  - A Systematic Review on the Sinomenine Derivatives.
AB  - Sinomenine is one of the most widely known alkaloids owing to different
      therapeutic properties including anti-inflammatory and immunosuppressive
      activities, as well as the potency in neurodegenerative disorders, such as
      Alzheimer's disease and Parkinson's disease. Sinomenine has been studied as a
      potential anti-inflammatory agent through appropriate structural modifications.
      Recently, a number of such approaches have been attempted in various laboratories
      with great success. Several series of derivatives have been synthesized with
      changes at rings A, B, C and D. Herein, we present an up to date review of
      modifications and bioactivities of important modified derivatives. These studies
      offer interesting knowledge on the bioactivity and structural specificity of
      sinomenine, providing better understanding of the structure-activity
      relationships (SAR) between designing and development of sinomenine derivative
      with better therapeutic and lower side effects.

PMID- 29173169
TI  - CRISPR/Cas9 Gene Editing: From Basic Mechanisms to Improved Strategies for
      Enhanced Genome Engineering In Vivo.
AB  - INTRODUCTION: Targeted genome editing using the CRISPR/Cas9 technology is
      becoming a major area of research due to its high potential for the treatment of
      genetic diseases. Our understanding of this approach has expanded in recent years
      yet several new challenges have presented themselves as we explore the boundaries
      of this exciting new technology. Chief among these is improving the efficiency
      but also the preciseness of genome editing. The efficacy of CRISPR/Cas9
      technology relies in part on the use of one of the major DNA repair pathways,
      Homologous recombination (HR), which is primarily active in S and G2 phases of
      the cell cycle. Problematically, the HR potential is highly variable from cell
      type to cell type and most of the cells of interest to be targeted in vivo for
      precise genome editing are in a quiescent state. CONCLUSION: In this review, we
      discuss the recent advancements in improving targeted CRISPR/Cas9 based genome
      editing and the promising ways of delivering this technology in vivo to the cells
      of interest.

PMID- 29173171
TI  - New Developments in CRISPR/Cas-based Functional Genomics and their Implications
      for Research Using Zebrafish.
AB  - INTRODUCTION: Genome editing using CRISPR/Cas9 has advanced very rapidly in its
      scope, versatility and ease of use. Zebrafish (Danio rerio) has been one of the
      vertebrate model species where CRISPR/Cas9 has been applied very extensively for
      many different purposes and with great success. In particular, disease modeling
      in zebrafish is useful for testing specific gene variants for pathogenicity in a
      preclinical setting. Here we describe multiple advances in diverse species and
      systems that can improve genome editing in zebrafish. OBJECTIVE: To achieve
      temporal and spatial precision of genome editing, many new technologies can be
      applied in zebrafish such as artificial transcription factors, drug-inducible or
      optogenetically-driven expression of Cas9, or chemically-inducible activation of
      Cas9. Moreover, chemically- or optogenetically- inducible reconstitution of dead
      Cas9 (catalytically inactive, dCas9) can enable spatiotemporal control of gene
      regulation. In addition to controlling where and when genome editing occurs,
      using oligonucleotides allows for the introduction (knock-in) of precise
      modifications of the genome. CONCLUSION: We review recent trends to improve the
      precision and efficiency of oligo-based point mutation knock-ins and discuss how
      these improvements can apply to work in zebrafish. Similarly to how chemical
      mutagenesis enabled the first genetic screens in zebrafish, multiplexed sgRNA
      libraries and Cas9 can enable the next revolutionary transition in how genetic
      screens are performed in this species. We discuss the first examples and
      prospects of approaches using sgRNAs as specific and effective mutagens.
      Moreover, we have reviewed methods aimed at measuring the phenotypes of single
      cells after their mutagenic perturbation with vectors encoding individual sgRNAs.
      These methods can range from different cell-based reporters to single-cell RNA
      sequencing and can serve as great tools for high-throughput genetic screens.

PMID- 29173170
TI  - First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?
AB  - A prospective first-in-human Phase 1 CRISPR gene editing trial in the United
      States for patients with melanoma, synovial sarcoma, and multiple myeloma offers
      hope that gene editing tools may usefully treat human disease. An overarching
      ethical challenge with first-in-human Phase 1 clinical trials, however, is
      knowing when it is ethically acceptable to initiate such trials on the basis of
      safety and efficacy data obtained from pre-clinical studies. If the pre-clinical
      studies that inform trial design are themselves poorly designed - as a result of
      which the quality of pre-clinical evidence is deficient - then the ethical
      requirement of scientific validity for clinical research may not be satisfied. In
      turn, this could mean that the Phase 1 clinical trial will be unsafe and that
      trial participants will be exposed to risk for no potential benefit. To assist
      sponsors, researchers, clinical investigators and reviewers in deciding when it
      is ethically acceptable to initiate first-in-human Phase 1 CRISPR gene editing
      clinical trials, structured processes have been developed to assess and minimize
      translational distance between pre-clinical and clinical research. These
      processes draw attention to various features of internal validity, construct
      validity, and external validity. As well, the credibility of supporting evidence
      is to be critically assessed with particular attention to optimism bias,
      financial conflicts of interest and publication bias. We critically examine the
      pre-clinical evidence used to justify the first-inhuman Phase 1 CRISPR gene
      editing cancer trial in the United States using these tools. We conclude that the
      proposed trial cannot satisfy the ethical requirement of scientific validity
      because the supporting pre-clinical evidence used to inform trial design is
      deficient.

PMID- 29173172
TI  - Therapeutic Applications of CRISPR/Cas for Duchenne Muscular Dystrophy.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular
      disease caused by the lack of dystrophin due to mutations in the DMD gene. Since
      dystrophin is essential in maintaining the integrity of the sarcolemmal membrane,
      the absence of the protein leads to muscle damage and DMD disease manifestation.
      Currently, there is no cure with only symptomatic management available.
      OBJECTIVE: The most recent advancements in DMD therapies do not provide a
      permanent treatment for DMD. CRISPR/Cas technology poses as an attractive
      platform for DMD gene therapy both dependent and independent of the specific
      mutation. METHOD: CRISPR/Cas technology can be utilized independent of the
      patient mutation by modulating disease modifiers. Regarding DMD duplication
      mutations, full length dystrophin can be restored using a single sgRNA approach.
      For DMD deletion and point mutations, the open reading frame (ORF) can be
      restored by removing or reframing exon(s) to produce a shorter form of
      dystrophin. The full-length wildtype dystrophin can also be restored using
      homologous recombination (HR). The CRISPR/Cas components for these strategies
      were delivered in vivo using the adeno-associated virus (AAV) vector. RESULTS:
      The upregulation of a dystrophin homologue called utrophin can compensate for the
      lack of dystrophin protein, and has been successfully demonstrated in patient
      cells. Full-length dystrophin was restored in patient cells carrying duplication
      mutations. The shorter form and full-length dystrophin was recovered using CRISPR
      strategies in vitro and in vivo. CONCLUSIONS: Restoration of the wild type and
      shorter form of dystrophin highlights the therapeutic potential of CRISPR
      technology for DMD.

PMID- 29173173
TI  - AR Copy Number and AR Signaling-directed Therapies in Castrationresistant
      Prostate Cancer.
AB  - BACKGROUND: Adaptive upregulation of Androgen Receptor (AR) is the most common
      event involved in the progression from hormone sensitive to Castration-Resistant
      Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling
      directed therapies such as abiraterone and enzalutamide in CRPC patients.
      OBJECTIVE: In this review, we discuss general mechanisms of resistance to AR
      targeted therapies, with a focus on the role of AR Copy Number (CN). We reported
      methods and clinical applications of AR CN evaluation in tissue and liquid
      biopsy, thus to have a complete information regarding its role as predictive and
      prognostic biomarker. CONCLUSION: Outcomes of CRPC patients are reported to be
      highly variable as the consequence of tumor heterogeneity. AR CN could contribute
      to patient selection and tumor monitoring in CRPC treated with new anti-cancer
      treatment as abiraterone and enzalutamide. Further studies to investigate AR CN
      effect to these agents and its potential combination with other prognostic or
      predictive clinical factors are necessary in the context of harmonized clinical
      trial design.

PMID- 29173174
TI  - Autophagy after Subarachnoid Hemorrhage: Can Cell Death be Good?
AB  - BACKGROUND: Autophagy is a prosurvival, reparative process that maintainsww
      cellular homeostasis through lysosomal degradation of selected cytoplasmic
      components and programmed death of old, dysfunctional, or unnecessary cytoplasmic
      entities. According to growing evidence, autophagy shows beneficial effects
      following subarachnoid hemorrhage (SAH). SAH is considered one of the most
      devastating forms of stroke. METHODS: In this review lies in revealing the
      pathophysiological pathways and the effects of autophagy. Current results from
      animal studies will be discussed focusing on the effects of inhibitors and
      inducers of autophagy. In addition, this review discusses the clinical
      translation of potential neuropharmacological targets that can help prevent early
      brain injury (EBI) following SAH by incorporating programmed cell death into
      clinical management. RESULTS: Published data showed that autophagy mechanisms
      have a prosurvival effect to reduce apoptotic cell death after SAH. However, if
      SAH exceeds a certain stress threshold, autophagy mechanisms lead to increased
      apoptotic cell death, more brain injury, and worse outcome. CONCLUSION: Future
      investigation on the differences and molecular switches between protective
      mechanisms of autophagy and excessive "self-eating" autophagy leading to cell
      death is needed to achieve more insight into the complex pathophysiology of brain
      injury after SAH. If autophagy after SAH can be controlled to lead to beneficial
      effects only, as the physiological self-control mechanism, this could be an
      important target for treatment.

PMID- 29173176
TI  - The SIV Envelope Glycoprotein, Viral Tropism, and Pathogenesis: Novel Insights
      from Nonhuman Primate Models of AIDS.
AB  - BACKGROUND: Cellular tropism of human immunodeficiency virus (HIV-1) is closely
      linked to interactions between the viral envelope glycoprotein (Env) with CD4 and
      chemokine receptor family members, CCR5 and CXCR4. This interaction plays a key
      role in determining anatomic sites that are infected in vivo and the cascade of
      early and late events that result in chronic immune activation, immunosuppression
      and ultimately, AIDS. CD4+ T cells are critical to adaptive immune responses, and
      their early and rapid infection in gut lamina propria and secondary lymphoid
      tissues in susceptible hosts likely contributes to viral persistence and
      progression to disease. CD4+ macrophages are also infected, although their role
      in HIV-1 pathogenesis is more controversial. METHODS: Pathogenic infection by
      simian immunodeficiency viruses (SIV) in Asian macaques as models of HIV-1
      infection has enabled the impact of cellular tropism on pathogenesis to be
      directly probed. This review will highlight examples in which experimental
      interventions during SIV infection or the introduction of viral mutations have
      altered cellular tropism and, subsequently, pathogenesis. RESULTS: Alterations to
      the interaction of Env and its cellular receptors has been shown to result in
      changes to CD4 dependence, coreceptor specificity, and viral tropism for gut CD4+
      T cells and macrophages. CONCLUSION: Collectively, these findings have yielded
      novel insights into the critical role of the viral Env and tropism as a driver of
      pathogenesis and host control and have helped to identify new areas for targeted
      interventions in therapy and prevention of HIV-1 infection.

PMID- 29173177
TI  - Integrase Strand Transfer Inhibitors and the Emergence of Immune Reconstitution
      Inflammatory Syndrome (IRIS).
AB  - BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a major concern
      when starting highly active anti-retroviral therapy (HAART) in new patients and
      especially late presenters. This study attempts to identify risk factors for IRIS
      and investigate whether certain treatment regimens increase the probability of
      IRIS for patients at risk. METHODS: Retrospective single-centre study of HIV
      patients treated with HAART. RESULTS: A total of 417 patients were included. We
      identified 45 cases of IRIS in 37 patients; an incidence of 13.3 cases over 1000
      person-years. In univariate analysis, IRIS development was significantly
      associated with CDC stage, the presence of an opportunistic infection (OI) at
      diagnosis, CD4 cell count and viral load at diagnosis and HAART initiation and
      the use of integrase strand inhibitors (INSTIs). In multivariate analysis, INSTIs
      use (OR 2.89; 95%CI 1.26-6.64; p=0.012), CD4<=200/mm3 (OR 5.56; 95%CI 2.2-13.98;
      p<0.001), and the presence of an OI (OR 4.74; 95%CI 2.13-10.23; p=0.012) were
      independent risk factors. Among INSTI regimens, dolutegravir (OR 4.99 vs. NNRTI;
      95%CI 1.11-22.55; p=0.037) and elvitegravir (OR 4.82 vs. NNRTI; 95%CI 1.43-16.19;
      p=0.011) seem to carry increased risk. Mortality was 18.9% (7/37) for IRIS
      patients compared to 9.7% (37/380) in the non-IRIS group. Mortality at any given
      time during follow-up was significantly higher in the IRIS group (HR 3.2; 95%CI
      1.39-7.36; p=0.006). CONCLUSION: The use of INSTIs and especially DTG and EVG is
      associated with a higher probability for the development of IRIS in the
      background of late presentation and the presence of OIs. These data highlight the
      need for further research.

PMID- 29173178
TI  - Knowledge, Normative Beliefs and Attitudes Related to Recent HIV Infection among
      People who Inject Drugs in Athens, Greece.
AB  - BACKGROUND: Despite great improvements in prevention over the last years, much
      has to be done to reduce new human immunodeficiency virus (HIV) infections.
      Substantial evidence shows that the six-month period of recent HIV infection
      contributes disproportionately to HIV transmission. OBJECTIVE: This study aims to
      investigate knowledge, normative beliefs, and attitudes of people who inject
      drugs (PWID) regarding recent HIV infection. METHODS: People who inject drugs in
      Athens, Greece were recruited in the fifth round of a respondent- driven sampling
      program (ARISTOTLE). The participants were tested for HIV and answered a
      structured questionnaire, which also included items on knowledge, normative
      beliefs, and attitudes regarding recent infection to address needs of the social
      network-based Transmission Reduction Intervention Project. The multivariable
      analyses included logistic regression models, which produced odds ratios (OR) and
      95% confidence intervals (CI). RESULTS: In total, 1,407 people (mean age: 36.3 +/
      7.9 years old; males: 81.9%) took part in the fifth round of ARISTOTLE. Of
      these, 61.5% knew that HIV-infected people who are not on treatment are more
      likely to transmit HIV during the first six months of their infection and 58.4%
      reported that people in their network would react positively towards a recently
      HIV-infected person. People who inject drugs who were knowledgeable of recent HIV
      infection were more likely to disagree with statements such as that one should
      avoid all contact with a person recently infected by HIV (adjusted OR: 1.510, 95%
      CI: 1.090, 2.091) or more likely to agree with statements such as that an HIV+
      person is much less likely to transmit HIV when h/she is on combination
      antiretroviral treatment (adjusted OR: 2.083, 95% CI: 1.231, 3.523). CONCLUSION:
      A considerable proportion of PWID in Athens, Greece, were aware of the high HIV
      transmission risk of recent HIV infection, although improvement is needed for
      some population segments. People who inject drugs who were knowledgeable of the
      role of recent HIV infection were more likely to have normative beliefs and
      attitudes that favor behaviors that could help rather than harm or stigmatize
      people who have recently been infected with HIV. Interventions that are based on
      the role of recent HIV infection in HIV transmission could be important to HIV
      prevention.

PMID- 29173179
TI  - SIV Coreceptor Specificity in Natural and Non-Natural Host Infection:
      Implications for Cell Targeting and Differential Outcomes from Infection.
AB  - Pathogenic HIV-1 infection of humans and SIVmac infection of macaques are the
      result of zoonotic transfer of primate immunodeficiency viruses from their
      natural hosts into non-natural host species. Natural host infections do not
      result in pathogenesis despite high levels of virus replication, and evidence
      suggests that differences in anatomical location and specific subsets of CD4+ T
      cells infected may underlie distinct outcomes from infection. The coreceptor CCR5
      has long been considered the sole pathway for SIV entry and the key determinant
      of CD4+ cell targeting, but it has also been known that natural hosts express
      exceedingly low levels of CCR5 despite maintaining high levels of virus
      replication. This review details emerging data indicating that in multiple
      natural host species, CCR5 is dispensable for SIV infection ex vivo and/or in
      vivo and, contrary to the established dogma, alternative coreceptors,
      particularly CXCR6, play a central role in infection and cell targeting.
      Infections of non-natural hosts, however, are characterized by CCR5-exclusive
      entry. These findings suggest that alternative coreceptor-mediated cell targeting
      in natural hosts, combined with low CCR5 expression, may direct the virus to
      distinct populations of cells that are dispensable for immune homeostasis,
      particularly extralymphoid and more differentiated CD4+ T cells. In contrast,
      CCR5-mediated entry in non-natural hosts results in targeting of CD4+ T cells
      that are located in lymphoid tissues, critical for immune homeostasis, or
      necessary for gut barrier integrity. Thus, fundamental differences in viral entry
      coreceptor use may be central determinants of infection outcome. These findings
      redefine the normal SIV/host relationship in natural host species, shed new light
      on key features linked to zoonotic immunodeficiency virus transfer, and highlight
      important questions regarding how and why this coreceptor bottleneck occurs and
      the coevolutionary equilibrium is lost following cross-species transfer that
      results in AIDS.

PMID- 29173181
TI  - Misoprostol-induced Acute Coronary Syndrome in a Premenopausal Woman: A Case
      Report with Literature Review.
AB  - BACKGROUND: Misoprostol is a synthetic analog of prostaglandin-E1 and it is the
      most widely used drug for the medical management of incomplete abortion. Acute
      Coronary Syndrome (ACS) rarely occurs in perimenopausal women, in addition, its
      presentation is atypical, so the disease is not always recognized. CASE REPORT:
      We describe a case of 39-year-old woman with no major underlying cardiovascular
      risk factors, who developed an episode of ACS following the administration of two
      doses of misoprostol. After the discontinuation of misoprostol treatment, there
      was a complete resolution of patient's symptoms. The case draws attention to a
      rare side effect of a commonly used drug and alerts the clinicians to be cautious
      in those patients having baseline risk factors which make the patient more
      susceptible to such serious adverse drug effect.

PMID- 29173175
TI  - Imaging the Role of Inflammation in Mood and Anxiety-related Disorders.
AB  - BACKGROUND: Studies investigating the impact of a variety of inflammatory stimuli
      on the brain and behavior have reported evidence that inflammation and release of
      inflammatory cytokines affect circuitry relevant to both reward and threat
      sensitivity to contribute to behavioral change. Of relevance to mood and anxiety
      related disorders, biomarkers of inflammation such as inflammatory cytokines and
      acute-phase proteins are reliably elevated in a significant proportion of
      patients with major depressive disorder (MDD), bipolar disorder, anxiety
      disorders and post-traumatic stress disorder (PTSD). METHODS: This review
      summarized clinical and translational work demonstrating the impact of peripheral
      inflammation on brain regions and neurotransmitter systems relevant to both
      reward and threat sensitivity, with a focus on neuroimaging studies involving
      administration of inflammatory stimuli. Recent translation of these findings to
      further understand the role of inflammation in mood and anxiety-related disorders
      is also discussed. RESULTS: Inflammation was consistently found to affect basal
      ganglia and cortical reward and motor circuits to drive reduced motivation and
      motor activity, as well as anxiety-related brain regions including amygdala,
      insula and anterior cingulate cortex, which may result from cytokine effects on
      monoamines and glutamate. Similar relationships between inflammation and altered
      neurocircuitry have been observed in MDD patients with increased peripheral
      inflammatory markers, and such work is on the horizon for anxiety disorders and
      PTSD. CONCLUSION: Neuroimaging effects of inflammation on reward and threat
      circuitry may be used as biomarkers of inflammation for future development of
      novel therapeutic strategies to better treat mood and anxiety-related disorders
      in patients with high inflammation.

PMID- 29173182
TI  - Lupus Nephritis: Current Treatment Paradigm and Unmet Needs.
AB  - BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder
      characterized by chronic inflammation, which can result in a multitude of
      systemic or organ-limited manifestations, including the skin, lungs, heart, and
      kidney. SLE nephritis is present in an average of 38% of patients at the time of
      diagnosis, and may occur as the initial presentation of disease with progression
      to End-Stage Renal Disease (ESRD) in roughly 10-20% of patients. METHODS: A
      review of the current literature was undertaken to investigate the evolution of
      treatment of SLE nephritis based on randomized trials and robust observational
      studies. We aimed to provide a timeline of the development of current induction
      and maintenance therapy, as well as the development of novel targeted therapies,
      all leading to current guidelines. RESULTS: Based on all available current data
      on standard of care therapies for SLE nephritis, there is at best a complete
      remission rate of 50-60%, and roughly 13-25% of patients experience periods of
      relapse during maintenance therapy for SLE nephritis. Therefore, the need for
      newer, targeted therapies has been the focus of many current, ongoing clinical
      trials. CONCLUSION: Standard induction and maintenance therapies at present are
      anti-proliferative and nonspecific, that is, interfering with the process of
      autoantigen presentation and activation of autoreactive leukocytes. However,
      newer agents with specific T-cell, B-cell, or proteasome targets are currently
      being investigated.

PMID- 29173180
TI  - The Neutralizing Antibody Response to the HIV-1 Env Protein.
AB  - BACKGROUND: A vaccine able to elicit broadly neutralizing antibodies capable of
      blocking infection by global viruses has not been achieved, and remains a key
      public health challenge. OBJECTIVE: During infection, a robust strain-specific
      neutralizing response develops in most people, but only a subset of infected
      people develop broadly neutralizing antibodies. Understanding how and why these
      broadly neutralizing antibodies develop has been a focus of the HIV-1 vaccine
      field for many years, and has generated extraordinary insights into the
      neutralizing response to HIV-1 infection. RESULTS: This review describes the
      features, targets and developmental pathways of early strainspecific antibodies
      and later broadly neutralizing antibodies, and explores the reasons such broad
      antibodies are not more commonly elicited during infection. CONCLUSION: The
      insights from these studies have been harnessed for the development of pioneering
      new vaccine approaches that seek to drive B cell maturation towards breadth.
      Overall, this review describes how findings from infected donors have impacted on
      active and passive immunization approaches that seek to prevent HIV-1 infection.

PMID- 29173183
TI  - A comparison of fucoidan conjugated to paclitaxel and curcumin for the dual
      delivery of cancer therapeutic agents.
AB  - The aim of this study was to develop and compare polymeric micelles of fucoidan,
      a sulfated polysaccharide, and hydrophobic drugs such as paclitaxel and curcumin.
      Paclitaxel and curcumin are both known for their medicinal properties, including
      anticancer efficacy. However, their very low water solubility, absorption and
      rapid metabolism leads to reduced bioavailability. To redress these problems and
      enhance anti-cancer therapeutics using fucoidan, polymeric micelles were
      synthesized from conjugates of fucoidan and hydrophobic drugs. The chemical
      conjugation of fucoidan and hydrophobic drugs has been achieved by utilizing
      reactive functional groups on the molecules, such as carboxylic groups and
      hydroxyl groups. The micelles revealed a homogeneous spherical morphology, size,
      negative surface charge. Fourier transform infrared spectroscopy was used to
      investigate the physicochemical properties of the polymeric micelles, which form
      a self-assembled polymeric micelle in aqueous medium. The results of the in vitro
      release of curcumin and fucoidan showed that their release rates were higher at a
      pH of 4.5 than at a pH of 7.4. In contrast, the paclitaxel conjugate had a
      similar release profile at pH of 4.5 and pH of 7.4. In the present work, we also
      found an effective drug delivery system that had the ability to release two types
      of anticancer drugs, fucoidan and hydrophobic drugs, in the tumour environment.

PMID- 29173184
TI  - Natural Compounds in the Chemoprevention of Malignant Melanoma.
AB  - Malignant melanoma is a very aggressive form of skin cancer, with increasing
      rates every year, with an etiology that derives from the transformation and
      uncontrolled growth of melanocytes. There are several treatment options which can
      be used as unique treatment or combined, depending upon the stage of melanoma
      including surgical excision, chemotherapy, immunotherapy, targeted therapy. Plant
      Kingdom displays an unequalled potential for the synthesis of highly diversified
      chemical structures. Although natural compounds are synthesized in order to help
      the plant to interact with the environment, a large number of phytochemicals act
      as drugs within the human or animal body by activating various biochemical
      pathways. The study aims to review another approach in the management of this
      highly aggressive form of skin cancer, namely the effect of natural compounds in
      the chemoprevention of malignant melanoma.

PMID- 29173185
TI  - A Review on Melatonin's Effects in Cancer: Potential Mechanisms
AB  - This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy
      tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal
      gland secretory product, an evolutionarily highly conserved molecule; it is also
      an antioxidant and an impressive protector of mitochondrial bioenergetic
      activity. MLT is characterized by an ample range of activities, modulating the
      physiology and molecular biology of the cell. Its physiological functions relate
      principally to the interaction of G protein-coupled MT1 and MT2 trans-membrane
      receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has
      been demonstrated to suppress the growth of various tumours both, in vivo and in
      vitro. In this review, we analyze in depth, the antioxidant activity of
      melatonin, aiming to illustrate the cancer treatment potential of the molecule,
      by limiting or reversing the changes occurring during cancer development and
      growth.

PMID- 29173186
TI  - Comparison of Physicochemical Properties of Generic Doxorubicin HCl Liposome
      Injection with the Reference Listed Drug.
AB  - BACKGROUND: Liposomal doxorubicin is widely used for treating ovarian cancer and
      Kaposi's sarcoma. Encapsulation of doxorubicin in highly complex polyethylene
      glycol-coated (stealth) liposomes prolongs residence time and avoids the systemic
      toxicity associated with administration of the free drug. Small variations in
      physicochemical properties introduced during manufacture of liposomes can
      influence the payload of encapsulated drug, stability of liposomes under
      physiological conditions, and release of drug at the target tissue. Accordingly,
      the US Food and Drug Administration and the European Medicines Agency have issued
      guidance for manufacturers of generic liposomal doxorubicin that is designed to
      ensure that more than 30 physicochemical parameters that influence its safety and
      efficacy should be similar in the generic and reference listed drugs. OBJECTIVE:
      This study aims to describe the physicochemical characterization procedures used
      to ensure consistency between batches of generic liposomal doxorubicin and with
      the reference listed drug. METHODS: A range of spectroscopic, chromatographic,
      and other physicochemical tests was used to compare relative concentrations of
      liposome components, liposome morphology, ratios of free/entrapped doxorubicin,
      stability, and in vitro doxorubicin release rates in physiologically and
      clinically relevant media. RESULTS: The tests established that generic and
      reference liposomes contained similar concentrations of drug, lipids, and
      excipients and that their physical forms were also similar. CONCLUSION: The
      results of the tests demonstrate the physicochemical equivalence of generic
      liposomal doxorubicin hydrochloride and the reference listed drug,
      Doxil(r)/Caelyx(r). Biochemical and clinical equivalence must also be
      demonstrated to fully meet regulatory requirements for generic liposomal
      medicines, and these are the subjects of separate studies.

PMID- 29173187
TI  - Trichinella spiralis and tumors: cause, coincidence or treatment?
AB  - Conventional therapeutic strategies for tumors have had limited success, and
      innovative and more effective approaches to treatment are urgently required. The
      ancient idea that various biological, bacterial, yeast, viral, and parasitic
      agents can be used as cancer therapeutics has gradually attracted considerable
      interest. Certain parasites have been widely discussed in association with human
      and animal tumors. Many researches have provided proofs that Trichinella spiralis
      (T. spiralis) possesses antitumor activities. The antitumor effect of T. spiralis
      was first described in the 1970s. However, its research has been inconsistent,
      and little progress has been made in this field. Therefore, the mechanisms
      underlying these inhibitory effects are still unclear, and convincing evidence of
      the links between T. spiralis and the prevention or treatment of tumors from
      clinical trials is absent. Meanwhile, some other researches also suggested that
      T. spiralis may cause or contribute to coinfection with a tumors. In this review,
      evidence for T. spiralis to act as a pro- or antitumorigenic agent is summarized
      and discussed, in hope of contributing to a better understanding of the relations
      between T. spiralis and tumors.

PMID- 29173188
TI  - Innate Immune Surveillance in the Central Nervous System Following Legionella
      pneumophila Infection.
AB  - BACKGROUND & OBJECTIVE: The innate immune response is a common occurrence in many
      neuroinflammatory diseases. Central Nervous System (CNS) resident immune cells
      are able to detect and react to infections and sterile trauma. Peripheral immune
      cell migration into CNS is regulated by the blood-brain barrier, although
      peripheral immune cells can invade CNS through meninges, choroid plexus,
      perivascular spaces, and cerebrospinal fluid. Consequently, in the brain, immune
      reactions can be mediated by both resident and peripheral immune cells. Both in
      the periphery and within the CNS, innate immune response is regulated by a wide
      array of pattern recognition receptors, including Tolllike, scavenger, Retinoic
      Acid-inducible Gene-1 like, and nucleotide-binding oligomerization domainslike
      responsible for inflammasome formation. Inflammasome pathway activation induces
      pyroptosis, a highly inflammatory cell death pattern that occurs to remove
      intracellular pathogens. Legionella pneumophila is an intracellular microorganism
      responsible for Legionnaires' disease, a lung infection always associated to
      neurological dysfunctions. Recent studies have been shown that Toll-like
      receptors, nucleotide-binding oligomerization domains-like receptors, and RIG-1
      like, are activated by L. pneumophila. This flagellated bacterium is able to
      replicate in phagocytic cells, including macrophages and microglia, responding by
      activating inflammasome pathways that may be the cause of CNS dysfunction
      detected in several infected patients. CONCLUSION: The aim of this review is to
      bring together the latest findings concerning L. pneumophila infection and innate
      immune host cell responses. A deeper knowledge of these processes could allow the
      use of immunomodulatory compounds able to counteract CNS involvement following L.
      pneumophila infection.

PMID- 29173189
TI  - Quality of Life in Individuals Affected by Arnold Chiari Malformation: Comparison
      and Validation of a Measurement Instrument.
AB  - BACKGROUND: Introduction. Arnold Chiari Malformation (ACM) type I is a pathology
      whose symptomatology has repercussions for the quality of life of those affected
      by it. Quality-of-life measurement instruments can allow the severity of the
      impact of Chiari type I malformation on patients' lives to be monitored. The
      Chiari Symptom Profile (CSP) is a valid and reliable instrument designed for this
      purpose. The aim of the study was to adapt the CSP to Spanish and to explore the
      reliability and validity of this construct in the context of Spanish-speaking
      patients with ACM. METHODS: The English CSP instrument has a good internal
      validity and consistency. We used a standardized procedure for the linguistic
      validation of the translated scale. For the psychometric validation, we recruited
      215 individuals with ACM and calculated the Cronbach's alpha for the sample. The
      construct was validated by analyzing the age, sex, and presence of syringomyelia,
      as well as by correlating the results with the sickness impact profile 30 (SIP
      30) questionnaire, which can also evaluate quality of life in this type of
      patient. RESULTS: The Spanish version of the CSP has good internal consistency
      and validity (Cronbach's alpha of 0.90); age, sex, and the presence of
      syringomyelia does not significantly affect the quality of life of patients with
      ACM. There was a direct and significant correlation between the Spanish CSP and
      the validated SIP-30 questionnaire results (p < 0.05). Further analysis showed a
      positive correlation for the physical and psychological scopes of the CSP and SIP
      30 questionnaires, but not for their functional and social scopes. CONCLUSION:
      This version of the CSP is a valid and reliable instrument for measuring quality
      of life in patients with ACM in the Spanish context.

PMID- 29173190
TI  - Migraine in Systemic Autoimmune Diseases.
AB  - BACKGROUND AND OBJECTIVE: Migraine and systemic autoimmune diseases are 2-3-fold
      more common in women and various studies have reported an association between the
      two pathologies. METHODS: This review takes into account epidemiological studies
      involving migraine and systemic lupus erythematosus, antiphospholipid syndrome,
      Sjogren's syndrome, and other diffuse connective tissue diseases. This scientific
      literature analysis consists of the main articles found in Medline with a search
      up to April 2017. RESULTS: Many epidemiological studies were carried out on
      patients suffering from systemic lupus erythematosus. Results showed that
      headache and migraine are more prevalent in systemic lupus erythematosus patients
      compared to controls, especially migraine with aura. Patients with Lupus and
      migraine show a higher lupus activity and association with Raynaud and/or
      antiphospholipids in these populations are contradictory. There are not enough
      data to establish an association between antiphospholipid syndrome and migraine.
      However, data are more consistent between antiphospholipid carrier condition and
      migraine. Systemic sclerosis is a rare disease, for this reason the amount of
      available data on this disorder are scanty. However, some studies reported an
      association between headache, migraine and systemic sclerosis, especially where
      gliotic brain lesions and Raynaud are coexisting. Finally, large propensity
      cohort population based studies suggested that systemic autoimmune diseases are
      more frequent in patients suffering from migraine. CONCLUSION: An attempt at
      explaining the possible link between these disorders and migraine is discussed at
      the end of the review. Several autoimmune alterations are shared by most
      autoimmune diseases and headache types. Endothelial dysfunction is the only
      alteration that is common among all these disorders.

PMID- 29173191
TI  - Relevant Patented Biotechnological Applications of Ecotin : An Update.
AB  - BACKGROUND: Ecotins are serine protease inhibitors which are generally found in
      the periplasmic compartment. These inhibitors act on a wide range of serine
      proteases with different efficiencies. Actually, only few Ecotins were studied,
      and the main characterized proteins derived from Escherichia coli. Functional
      studies of this latter protein allowed the development of numerous patents
      related to Ecotin relevant biotechnological applications. OBJECTIVE: This review
      aims to give an update on the relevant Ecotins already described and to provide a
      concise overview concerning the relevant patented applications of these serine
      protease inhibitors. METHOD: In this review, we focus on the analysis of Ecotin
      diversity and their distribution using Pfam protein data base. Moreover, we
      report a detailed overview regarding the biotechnological applications of the
      Ecotins based on all patents associated to Ecotins and their biotechnological
      applications searched in European Patent Office (Espacenet), United States Patent
      and National Patent Collections (WIPO) patents databases. RESULTS: On the basis
      of this analysis we demonstrate that Ecotins are mostly present in bacteria.
      Study of Ecotin sequences and their biochemical properties reveals that they are
      a small serine protease inhibitor group. The high stability and specificity of
      Ecotins promote their biotechnological uses in several fields. The original
      structure organization of Ecotin-protease complexes and their flexibility leads
      to several patented applications. CONCLUSION: This review showed that Ecotins
      have many attractive biotechnological applications. Potential of Ecotins needs to
      be more investigated seeing the limited available data related to this protein
      family. Thus, further functional analyses will promote the use of Ecotins.

PMID- 29173192
TI  - The Ecstacy of Gold: Patent Expirations for Trastuzumab, Bevacizumab, Rituximab,
      and Cetuximab.
AB  - OBJECTIVE: Fully humanized monoclonal antibodies have revolutionized the
      treatment of many solid tumors, including ovarian, lung, colorectal, and breast
      cancer. Among the most widely used monoclonal antibodies in clinical oncology are
      cetuximab, trastuzumab, rituximab, and bevacizumab. METHODS: This is a review
      article focusing on the drug patents for cetuximab, trastuzumab, rituximab, and
      bevacizumab. RESULTS: These four monoclonal antibodies are used in both first and
      second line treatment regimens for multiple common malignancies. With recent
      patent expirations, pharmaceutical companies involved in biosimilar manufacture
      are looking to establish ownership over these financial monopolies. CONCLUSION:
      This article will review these four notable monoclonal antibodies, their role in
      clinical oncology, and the drug patents that are nearing expiration. There are
      currently only two biosimilars approved in the United States: the trastuzumab
      biosimilar trastuzumab-dkst (Ogivri) and the bevacizumab biosimilar bevacizumab
      awwb (Mvasi). In Europe, SB3, a trastuzumab biosimilar, is approved for use as
      well as two rituzimab biosimilars, truxima and rixathon.

PMID- 29173194
TI  - Sex similarities and differences in risk factors for recurrence of major
      depression.
AB  - BACKGROUND: Major depression (MD) occurs about twice as often in women as in men,
      but it is unclear whether sex differences subsist after disease onset. This study
      aims to elucidate potential sex differences in rates and risk factors for MD
      recurrence, in order to improve prediction of course of illness and understanding
      of its underlying mechanisms. METHODS: We used prospective data from a general
      population sample (n = 653) that experienced a recent episode of MD. A diverse
      set of potential risk factors for recurrence of MD was analyzed using Cox models
      subject to elastic net regularization for males and females separately. Accuracy
      of the prediction models was tested in same-sex and opposite-sex test data.
      Additionally, interactions between sex and each of the risk factors were
      investigated to identify potential sex differences. RESULTS: Recurrence rates and
      the impact of most risk factors were similar for men and women. For both sexes,
      prediction models were highly multifactorial including risk factors such as
      comorbid anxiety, early traumas, and family history. Some subtle sex differences
      were detected: for men, prediction models included more risk factors concerning
      characteristics of the depressive episode and family history of MD and
      generalized anxiety, whereas for women, models included more risk factors
      concerning early and recent adverse life events and socioeconomic problems.
      CONCLUSIONS: No prominent sex differences in risk factors for recurrence of MD
      were found, potentially indicating similar disease maintaining mechanisms for
      both sexes. Course of MD is a multifactorial phenomenon for both males and
      females.

PMID- 29173193
TI  - Polygenic prediction of the phenome, across ancestry, in emerging adulthood.
AB  - BACKGROUND: Identifying genetic relationships between complex traits in emerging
      adulthood can provide useful etiological insights into risk for psychopathology.
      College-age individuals are under-represented in genomic analyses thus far, and
      the majority of work has focused on the clinical disorder or cognitive abilities
      rather than normal-range behavioral outcomes. METHODS: This study examined a
      sample of emerging adults 18-22 years of age (N = 5947) to construct an atlas of
      polygenic risk for 33 traits predicting relevant phenotypic outcomes. Twenty
      eight hypotheses were tested based on the previous literature on samples of
      European ancestry, and the availability of rich assessment data allowed for
      polygenic predictions across 55 psychological and medical phenotypes. RESULTS:
      Polygenic risk for schizophrenia (SZ) in emerging adults predicted anxiety,
      depression, nicotine use, trauma, and family history of psychological disorders.
      Polygenic risk for neuroticism predicted anxiety, depression, phobia, panic,
      neuroticism, and was correlated with polygenic risk for cardiovascular disease.
      CONCLUSIONS: These results demonstrate the extensive impact of genetic risk for
      SZ, neuroticism, and major depression on a range of health outcomes in early
      adulthood. Minimal cross-ancestry replication of these phenomic patterns of
      polygenic influence underscores the need for more genome-wide association studies
      of non-European populations.

PMID- 29173195
TI  - Primary versus secondary tracheoesophageal puncture: systematic review and meta
      analysis.
AB  - BACKGROUND: Tracheoesophageal puncture represents the 'gold standard' for voice
      restoration following laryngectomy. Tracheoesophageal puncture can be undertaken
      primarily during laryngectomy or in a separate secondary procedure. There is no
      current consensus on which approach is superior. The current evidence comparing
      primary and secondary tracheoesophageal puncture was assessed. METHODS: A
      systematic review and meta-analysis of articles comparing outcomes for primary
      and secondary tracheoesophageal puncture after laryngectomy were conducted.
      Outcome measures were: voice success, overall complication rate and
      pharyngocutaneous fistula rate. RESULTS: Eleven case series met the inclusion
      criteria, two prospective and nine retrospective. Meta-analysis did not
      demonstrate statistically significant differences in overall complication rate or
      voice outcomes, though it suggested a significantly increased risk of
      pharyngocutaneous fistula in primary compared to secondary tracheoesophageal
      puncture. CONCLUSION: Primary tracheoesophageal puncture is a safe and efficient
      approach for voice rehabilitation. However, secondary tracheoesophageal puncture
      should be preferred where there is a higher risk of pharyngocutaneous fistula.

PMID- 29173196
TI  - Person-fit feedback on inconsistent symptom reports in clinical depression care.
AB  - BACKGROUND: Depressive patients can present with complex and different symptom
      patterns in clinical care. Of these, some may report patterns that are
      inconsistent with typical patterns of depressive symptoms. This study aimed to
      evaluate the validity of person-fit statistics to identify inconsistent symptom
      reports and to assess the clinical usefulness of providing clinicians with person
      fit score feedback during depression assessment. METHODS: Inconsistent symptom
      reports on the Inventory of Depressive Symptomatology Self-Report (IDS-SR) were
      investigated quantitatively with person-fit statistics for both intake and follow
      up measurements in the Groningen University Center of Psychiatry (n = 2036).
      Subsequently, to investigate the causes and clinical usefulness of on-the-fly
      person-fit alerts, qualitative follow-up assessments were conducted with three
      psychiatrists about 20 of their patients that were randomly selected. RESULTS:
      Inconsistent symptom reports at intake (12.3%) were predominantly characterized
      by reporting of severe symptoms (e.g. psychomotor slowing) without mild symptoms
      (e.g. irritability). Person-fit scores at intake and follow-up were positively
      correlated (r = 0.45). Qualitative interviews with psychiatrists resulted in an
      explanation for the inconsistent response behavior (e.g. complex comorbidity,
      somatic complaints, and neurological abnormalities) for 19 of 20 patients.
      Psychiatrists indicated that if provided directly after the assessment, a person
      fit alert would have led to new insights in 60%, and be reason for discussion
      with the patient in 75% of the cases. CONCLUSIONS: Providing clinicians with
      automated feedback when inconsistent symptom reports occur is informative and can
      be used to support clinical decision-making.

PMID- 29173197
TI  - Prevalence of breast-feeding and exclusive breast-feeding at 48 h after birth and
      up to the sixth month in Cyprus: the BrEaST start in life project.
AB  - OBJECTIVE: To assess the prevalence and sociodemographic determinants of breast
      feeding (BF) and exclusive breast-feeding (EBF) in Cyprus up to the sixth month.
      DESIGN: Cross-sectional and longitudinal descriptive study. BF and EBF were
      estimated based on mothers' self-reported BF status in line with Step 7 of the
      WHO/UNICEF Baby-Friendly Hospital Initiative questionnaire and based on 24 h
      recall. SETTING: Maternity wards in all public hospitals and twenty-nine (of
      thirty-five) private maternity clinics nationwide. SUBJECTS: Consecutive sample
      of 586 mothers recruited within 48 h from birth, followed up by telephone
      interview at the first, fourth and sixth month. RESULTS: Although 84.3 % of
      mothers initiated BF before discharge, prevalence of BF at the sixth month was
      32.4 %, with the highest reduction observed between the first and fourth months.
      Prevalence of EBF at 48 h was 18.8 % and fell gradually to 5.0 % at the sixth
      month. Mothers with higher educational attainment or higher family income were
      more likely to breast-feed until the sixth month. In terms of EBF, an association
      was observed only with education, which persisted until the sixth month. Other
      than social gradient, mode of delivery was the strongest determinant of BF
      initiation, exclusivity and continuation. Mothers who gave birth vaginally were
      three to four times more likely to initiate BF (OR=3.1; 95 % CI 1.7, 5.4) and EBF
      (OR=4.3; 95 % CI 2.7, 6.8). CONCLUSIONS: The low prevalence of BF and EBF in
      Cyprus, together with the fact that caesarean section rates are currently among
      the highest in Europe, suggest the need for further research to understand this
      multidimensional phenomenon and for interdisciplinary policy action to protect,
      promote and support BF.

PMID- 29173198
TI  - Maternal dietary supplementation with ferrous N-carbamylglycinate chelate affects
      sow reproductive performance and iron status of neonatal piglets.
AB  - Iron-deficiency anemia is a public health concern that frequently occurs in
      pregnant mammals and neonatal offspring. Ferrous N-carbamylglycinate chelate (Fe
      CGly) is a newly designed iron fortifier with proven effects in iron-deficient
      rats and weanling piglets. However, the effects of this new compound on pregnant
      mammals are unknown. Therefore, this experiment was conducted to evaluate the
      effects of Fe-CGly on sow reproductive performance and iron status of both sows
      and neonatal piglets. A total of 40 large-white sows after second parity were
      randomly assigned to two groups (n=20). They were receiving a diet including 80
      mg Fe/kg as FeSO4 or Fe-CGly, respectively, from day 85 of gestation to
      parturition. The serum (day 110 of pregnancy) and placentas of sows were sampled.
      Litter size, mean weight of live born piglets, birth (live) litter weight, number
      of live born piglets, and the number of still-born piglets, mummies, and weak
      born piglets were recorded. Once delivered, eight litters were randomly selected
      from the 20 litters per treatment, and one new-born male piglet (1.503+/-0.142
      kg) from each selected litter was slaughtered within 3 h after birth from the
      selected litters, without colostrum ingestion. The serum, longissimus muscle,
      liver and kidneys of the piglets were collected. The iron status of the serum
      samples and the messenger RNA level of iron-related genes in the placenta, liver
      and kidney were analyzed. The results showed that litter weight of live born
      piglets was higher (P=0.030) in the Fe-CGly group (19.86 kg) than in the FeSO4
      group (17.34 kg). Fe-CGly significantly increased placental iron concentration
      (P<0.05) of sows. It also significantly increased iron saturation and reduced the
      total iron-binding capacity of piglets (P<0.05) at birth. However, the results
      revealed that supplementation of Fe-CGly in sows reduced liver and kidney iron
      concentration of neonatal piglets (P<0.05), indicating decreased iron storage. In
      addition, the concentration of iron in the colostrum was not significantly
      changed. Therefore, the present results suggested that replacement of maternal
      FeSO4 supplement with Fe-CGly in the late-gestating period for sows could improve
      litter birth weight, probably via enhanced iron transportation in the placenta.

PMID- 29173199
TI  - Effects of prenatal n-3 fatty acid supplementation on offspring resolvins at
      birth and 12 years of age: a double-blind, randomised controlled clinical trial.
AB  - Resolution of inflammation is an active process involving specialised pro
      resolving mediators (SPM) generated from the n-3 fatty acids EPA and DHA. n-3
      Fatty acid supplementation during pregnancy may provide an intervention strategy
      to modify these novel SPM. This study aimed to assess the effect of n-3 fatty
      acid supplementation in pregnancy on offspring SPM at birth and 12 years of age
      (12 years). In all, ninety-eight atopic pregnant women were randomised to 3.7 g
      daily n-3 fatty acids or a control (olive oil), from 20 weeks gestation until
      delivery. Blood was collected from the offspring at birth and at 12 years. Plasma
      SPM consisting of 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins,
      17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14
      hydroxydocosahexaenoic acid (14-HDHA), 10 S,17S-dihydroxydocosahexaenoic acid,
      maresins and protectin 1, were measured by liquid chromatography-tandem MS. We
      identified the resolvins RvE1, RvE2, RvE3, RvD1, 17R-RvD1 and RvD2 for the first
      time in human cord blood. n-3 Fatty acids increased cord blood 18-HEPE (P<0.001)
      derived from EPA relative to the control group. DHA-derived 17-HDHA at birth was
      significantly increased in the n-3 fatty acid group relative to the controls
      (P=0.001), but other SPM were not different between the groups. n-3 Fatty acid
      supplementation during pregnancy was associated with an increase in SPM
      precursors in the offspring at birth but the effects were not sustained at 12
      years. The presence of these SPM, particularly at birth, may have functions
      relevant in the newborn that remain to be established, which may be useful for
      future investigations.

PMID- 29173200
TI  - New microsatellites revealed strong gene flow among populations of a new outbreak
      pest, Athetis lepigone (Moschler).
AB  - Athetis lepigone (Moschler) (Lepidoptera: Noctuidae) is a new outbreak pest in
      China. Consequently, it is unclear whether the emergence and spread of the
      outbreak of this pest are triggered by rapid in situ population size increases in
      each outbreak area, or by immigrants from a potential source area in China. In
      order to explore the outbreak process of this pest through a population genetics
      approach, we developed ten novel polymorphic expressed sequence tags (EST)
      derived microsatellites. These new microsatellites had moderately high levels of
      polymorphism in the tested population. The number of alleles per locus ranged
      from 3 to 19, with an average of 8.6, and the expected heterozygosity ranged from
      0.269 to 0.783. A preliminary population genetic analysis using these new
      microsatellites revealed a lack of population genetic structure in natural
      populations of A. lepigone. The estimates of recent migration rate revealed
      strong gene flow among populations. In conclusion, our study developed the first
      set of EST-microsatellite markers and shed a new light on the population genetic
      structure of this pest in China.

PMID- 29173201
TI  - Duration of untreated psychosis and neurocognitive functioning in first-episode
      psychosis: a systematic review and meta-analysis.
AB  - BACKGROUND: Previous reviews suggest there is minimal evidence for an association
      between duration of untreated psychosis (DUP) and neurocognition. This is based
      on tallied findings of studies with small samples and neurocognition viewed as a
      single construct. We aimed to conduct a systematic review and meta-analysis
      examining the association between DUP and individual neurocognitive domains and
      tests in first-episode psychosis (FEP). METHOD: MOOSE and PRISMA guidelines were
      followed. Forty-three studies involving 4647 FEP patients were included. For
      studies providing correlations between DUP and neurocognition, 12 separate meta
      analyses were performed based on neurocognitive domains/indices. The influence of
      demographic/clinical variables was tested using weighted linear meta-regression
      analyses. RESULTS: The relationship between DUP and most neurocognitive
      domains/indices was not significant. Longer DUP was associated with a larger
      cognitive deterioration index, i.e. current minus premorbid intellectual
      functioning (N = 4; mean ES -0.213, 95% confidence interval (CI) (-0.344 to 
      0.074), p = 0.003). Findings were homogeneous, with no evidence of publication
      bias or significant influence from moderators. For studies providing mean and
      standard deviations for neurocognitive measures and DUP, 20 meta-regressions were
      performed on individual neurocognitive tests. One significant finding emerged
      showing that longer DUP was associated with fewer Wisconsin Card Sorting Test
      perseverative errors (mean ES -0.031, 95% CI (-0.048 to -0.013), p < 0.001).
      Exploratory meta-regressions in studies with mean DUP <360 days showed longer DUP
      was significantly associated with poorer performance on Trail Making Test A and B
      and higher Full-Scale IQ. CONCLUSION: There may not be a generalised association
      between DUP and neurocognition, however, specific cognitive functions may be
      associated with longer DUP or delayed help-seeking.

PMID- 29173202
TI  - Necrotising otitis externa in the immunocompetent patient: case series.
AB  - BACKGROUND: Necrotising otitis externa can be a devastating form of otitis
      externa. It typically tends to affect patients who are immunocompromised or
      diabetic. To date, there is very little in the literature about necrotising
      otitis externa in the immunocompetent patient population. CASE REPORTS: The
      present paper discusses both the clinical and radiological findings in three
      cases of necrotising otitis externa in an immunocompetent patient cohort. The
      common factor among all three patients was their advanced age. CONCLUSION:
      Diagnosing necrotising otitis externa can be challenging because of the
      potentially non-specific symptoms and the absence of early radiological signs,
      particularly if patients are neither immunocompromised nor diabetic. Elderly
      patients should be considered in the same light as immunocompromised and diabetic
      patients in the context of necrotising otitis externa.

PMID- 29173204
TI  - Limitations of the Echinococcus granulosus genome sequence assemblies for
      analysis of the gene family encoding the EG95 vaccine antigen.
AB  - Echinococcus granulosus is an important zoonotic parasite that is distributed
      worldwide. The EG95 vaccine was developed to assist with control of E. granulosus
      transmission through the parasite's livestock intermediate hosts. The vaccine is
      based on a recombinant antigen encoded by a gene which is a member of a multi
      gene family. With the recent availability of two E. granulosus draft genomes, we
      sought to map the eg95 gene family to the genomes. We were unable to map
      unequivocally any of the eg95 gene family members which had previously been
      characterized by cloning and sequencing both strands of genomic DNA fragments.
      Our inability to map EG95-related genes to the genomes has revealed limitations
      in the assembled sequence data when utilized for gene family analyses. This study
      contrasts with the expectations expressed in often high-profile publications
      describing draft genomes of parasitic organisms, highlighting deficiencies in
      currently available genomic resources for E. granulosus and provides a cautionary
      note for research which seeks to utilize these genome datasets.

PMID- 29173203
TI  - 25(OH)D3-enriched or fortified foods are more efficient at tackling inadequate
      vitamin D status than vitamin D3.
AB  - The ability to synthesise sufficient vitamin D through sunlight in human subjects
      can be limited. Thus, diet has become an important contributor to vitamin D
      intake and status; however, there are only a few foods (e.g. egg yolk, oily fish)
      naturally rich in vitamin D. Therefore, vitamin D-enriched foods via
      supplementing the animals' diet with vitamin D or vitamin D fortification of
      foods have been proposed as strategies to increase vitamin D intake. Evidence
      that cholecalciferol (vitamin D3) and calcifediol (25(OH)D3) content of eggs,
      fish and milk increased in response to vitamin D3 supplementation of hens, fish
      or cows' diets was identified when vitamin D-enrichment studies were reviewed.
      However, evidence from supplementation studies with hens showed only dietary
      25(OH)D3, not vitamin D3 supplementation, resulted in a pronounced increase of
      25(OH)D3 in the eggs. Furthermore, evidence from randomised controlled trials
      indicated that a 25(OH)D3 oral supplement could be absorbed faster and more
      efficiently raise serum 25(OH)D concentration compared with vitamin D3
      supplementation. Moreover, evidence showed the relative effectiveness of
      increasing vitamin D status using 25(OH)D3 varied between 3.13 and 7.14 times
      that of vitamin D3, probably due to the different characteristics of the
      investigated subjects or study design. Therefore, vitamin D-enrichment or
      fortified foods using 25(OH)D3 would appear to have advantages over vitamin D3.
      Further well-controlled studies are needed to assess the effects of 25(OH)D3
      enriched or fortified foods in the general population and clinical patients.

PMID- 29173205
TI  - Effect of maternal dyslipidaemia on the cardiorespiratory physiology and
      biochemical parameters in male rat offspring.
AB  - The present study evaluated the effects of maternal dyslipidaemia on blood
      pressure (BP), cardiorespiratory physiology and biochemical parameters in male
      offspring. Wistar rat dams were fed either a control (CTL) or a dyslipidaemic
      (DLP) diet during pregnancy and lactation. After weaning, both CTL and DLP
      offspring received standard diet. On the 30th and 90th day of life, blood samples
      were collected for metabolic analyses. Direct measurements of BP, respiratory
      frequency (RF), tidal volume (VT) and ventilation (VE) under baseline condition,
      as well as during hypercapnia (7 % CO2) and hypoxia (KCN, 0.04 %), were recorded
      from awake 90-d-old male offspring. DLP dams exhibited raised serum levels of
      total cholesterol (TC) (4.0-fold), TAG (2.0-fold), VLDL+LDL (7.7-fold) and
      reduced HDL-cholesterol (2.4-fold), insulin resistance and hepatic steatosis at
      the end of lactation. At 30 d of age, the DLP offspring showed an increase in the
      serum levels of TC (P<0.05) and VLDL+LDL (P<0.05) in comparison with CTL
      offspring. At 90 d of age, DLP offspring exhibited higher mean arterial pressure
      (MAP, approximately 34 %). In the spectral analysis, the DLP group showed
      augmented low-frequency (LF) power and LF:high-frequency (HF) ratio when compared
      with CTL offspring. In addition, the DLP animals showed a larger delta variation
      in arterial pressure after administration of the ganglionic blocker (P=0.0003).
      We also found that cardiorespiratory response to hypercapnia and hypoxia was
      augmented in DLP offspring. In conclusion, the present data show that maternal
      dyslipidaemia alters cardiorespiratory physiology and may be a predisposing
      factor for hypertension at adulthood.

PMID- 29173206
TI  - Duration of untreated prodromal symptoms in a Chinese sample at a high risk for
      psychosis: demographic, clinical, and outcome.
AB  - BACKGROUND: The duration of untreated psychosis (DUP) has been widely studied.
      However, for individuals with attenuated psychosis syndrome (APS), it is unclear
      whether the duration of untreated prodromal symptoms (DUPrS) also has a negative
      effect on the progression of psychosis. Our aim was to identify demographic and
      clinical factors contributing to the DUPrS in a large sample of individuals with
      APS, and to evaluate the association between DUPrS and the conversion to
      psychosis. METHOD: A sample of 391 individuals with APS, who were identified
      through a structured interview for prodromal syndromes, were included in this
      study, of whom a total of 334 patients had completed at least a 1-year clinical
      follow-up. A total of 57 individuals had converted to psychosis. RESULTS: The
      average DUPrS was 4.8 months for the whole sample. Individuals with a longer
      DUPrS were likely to be men, non-local residents, with abnormal thought symptoms,
      a higher severity level of negative symptoms, the lower severity level of general
      symptoms, and lower level of general function before the onset of attenuated
      positive symptoms. A DUPrS of less than 2 months, or more than 6 months, lowered
      the risk for conversion to psychosis. CONCLUSIONS: Our data suggested that the
      association between the DUPrS and outcome in individuals with APS were likely to
      be different, which is either long or short DUPrS was not related to future
      psychosis onset. Individuals with APS were more likely to have a group of
      features associated with a longer DUPrS.

PMID- 29173207
TI  - Impact of an intervention programme on knowledge, attitudes and practices of
      population regarding severe fever with thrombocytopenia syndrome in endemic areas
      of Lu'an, China.
AB  - Knowledge, attitudes and practices (KAP) of the population regarding severe fever
      with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were
      assessed before and after an intervention programme. The pre-intervention phase
      was conducted using a sample of 425 participants from the 12 selected villages
      with the highest rates of endemic SFTS infection. A predesigned interview
      questionnaire was used to assess KAP. Subsequently, an intervention programme was
      designed and applied in the selected villages. KAP was re-assessed for each
      population in the selected villages using the same interview questionnaire.
      Following 2 months of the programme, 339 participants had completed the re
      assessed survey. The impact of the intervention programme was evaluated using
      suitable statistical methods. A significant increase in the KAP and total KAP
      scores was noted following the intervention programme, whereas the proportion of
      correct knowledge, the positive attitudes and the effective practices toward SFTS
      of respondents increased significantly. The intervention programme was effective
      in improving KAP level of SFTS in populations that were resident in endemic
      areas.

PMID- 29173208
TI  - Dietary supplementation with cysteine prevents adverse metabolic outcomes of
      repeated cures with paracetamol in old rats.
AB  - Cysteine (Cys), a conditionally indispensable amino acid, is required for the
      detoxification of paracetamol (acetaminophen, N-acetyl-para-aminophenol, 4
      hydroxy-acetanilide, APAP), a drug of widespread use in older persons. We
      recently reported that repeated APAP cures could worsen sarcopenia in old rats,
      likely to be due to the impairment of Cys/GSH homoeostasis. The aim of the study
      was to evaluate whether a dietary Cys supplementation during APAP cures could
      improve Cys/GSH homoeostasis and thus preserve skeletal muscle. Male 21.5-month
      old Wistar rats received three 2-week-long cures of APAP (1 % of diet) alone or
      with extra Cys (0.5 % of diet), intercalated with washout periods of 2 weeks
      (APAP and APAP-Cys groups, respectively). They were compared with untreated
      control rats (CT group). CT and APAP-Cys groups were pair-fed to the APAP group.
      Dietary Cys supplementation was efficient to prevent increase in liver mass
      (P<0.0001), decrease in liver GSH (P<0.0001), increase in blood GSH concentration
      (P<0.0001), and to some extent, decrease in plasma free Cys concentration
      (P<0.05), all induced by repeated APAP cures. The addition of Cys to APAP cures
      decreased plasma alanine transaminase (P<0.05), the fractional synthesis rate of
      liver proteins (P<0.01), and increased masses of extensor digitorum longus
      (P<0.01), and soleus (P<0.05), compared with the APAP group. Cys supplementation
      prevented alteration in Cys/GSH homoeostasis and increased some muscle masses in
      old rats under repeated cures with a non-toxic dose of APAP.

PMID- 29173209
TI  - Time-series responses of swine plasma metabolites to ingestion of diets
      containing myo-inositol or phytase.
AB  - The effect of the ingestion of diets containing either myo-inositol or exogenous
      phytase on plasma metabolites was examined using 29 kg barrows. The diets were:
      control (maize, soya, rapeseed, rice bran), control plus 2 g/kg myo-inositol,
      control plus 1000 phytase units (FYT)/kg or 3000 FYT/kg exogenous phytase. Pigs
      were housed in a PigTurn device and blood was collected, from jugular catheters,
      via an automated system at -30, (30 min before feeding), 0, 15, 30, 45, 60, 90,
      120, 150, 180, 240, 300 and 360 min post-feeding. The addition of 2 g/kg myo
      inositol to the basal diet resulted in an increase in plasma myo-inositol
      concentration that was evident 45-60 min after diet introduction and persisted to
      360 min post-feeding. Similarly, supplementation of the basal diet with either
      1000 or 3000 FYT/kg exogenous phytase resulted in an increase in plasma myo
      inositol concentration that was still rising 360 min post-feeding. Plasma P
      concentration was increased over time by the addition of 1000 and 3000 FYT/kg
      phytase, but not by the addition of myo-inositol. Other plasma metabolites
      examined were not affected by dietary treatment. It can be concluded that oral
      delivery of myo-inositol results in rapid increase in plasma myo-inositol
      concentrations that peak approximately 45-60 min after feeding. Use of
      supplemental phytase achieves similar increases in myo-inositol concentration in
      plasma but the appearance is more gradual. Furthermore, supplementation of pig
      diets with exogenous phytase results in rapid appearance of P in plasma that may
      be sustained over time relative to diets with no added phytase.

PMID- 29173211
TI  - Associations between Trauma, Dissociation, Adult Attachment and Proneness to
      Hallucinations.
AB  - BACKGROUND: Childhood adversity, dissociation and adult attachment have all been
      implicated in the development of hallucinations or 'voice-hearing'. Testing
      psychological models in relation to subclinical phenomena, such as proneness to
      hallucinations in non-clinical samples, provides a convenient methodology to
      develop understanding of the processes and mechanisms underlying clinical
      symptoms. AIMS: This paper investigates the relative contribution of childhood
      adversity, dissociation and adult attachment in explaining hallucination
      proneness in a non-clinical sample. METHODS: Students and staff with no previous
      contact with secondary care at the University of Manchester were recruited.
      Participants completed a series of self-report measures: the Launay-Slade
      Hallucination Scale (LSHS), the Relationship Scale Questionnaire (RSQ), the
      Childhood Trauma Questionnaire (CTQ), the Dissociative Experiences Schedule (DES
      II) and the Positive and Negative Affect Schedule (PANAS). RESULTS: As
      hypothesized, insecure attachment, childhood adversity and dissociative symptoms
      were correlated with hallucination proneness. Multiple regression analysis,
      controlling for confounds of age and negative affect, indicated that the RSQ, CTQ
      and DES II predicted hallucination proneness. Only DES II and RSQ avoidant
      attachment were significant independent predictors in the final model.
      CONCLUSIONS: This study provides further evidence to support the idea that
      attachment and dissociation are important psychological mechanisms involved in
      voice-hearing proneness. Further testing is required with a clinical population.

PMID- 29173210
TI  - Psychosocial functioning among regular cannabis users with and without cannabis
      use disorder.
AB  - BACKGROUND: In the United States, cannabis accessibility has continued to rise as
      the perception of its harmfulness has decreased. Only about 30% of regular
      cannabis users develop cannabis use disorder (CUD), but it is unclear if
      individuals who use cannabis regularly without ever developing CUD experience
      notable psychosocial impairment across the lifespan. Therefore, psychosocial
      functioning was compared across regular cannabis users with or without CUD and a
      non-user control group during adolescence (age 17; early risk) and young
      adulthood (ages 18-25; peak CUD prevalence). METHOD: Weekly cannabis users with
      CUD (n = 311), weekly users without CUD (n = 111), and non-users (n = 996) were
      identified in the Minnesota Twin Family Study. Groups were compared on alcohol
      and illicit drug use, psychiatric problems, personality, and social functioning
      at age 17 and from ages 18 to 25. Self-reported cannabis use and problem use were
      independently verified using co-twin informant report. RESULTS: In both
      adolescence and young adulthood, non-CUD users reported significantly higher
      levels of substance use problems and externalizing behaviors than non-users, but
      lower levels than CUD users. High agreement between self- and co-twin informant
      reports confirmed the validity of self-reported cannabis use problems.
      CONCLUSIONS: Even in the absence of CUD, regular cannabis use was associated with
      psychosocial impairment in adolescence and young adulthood. However, regular
      users with CUD endorsed especially high psychiatric comorbidity and psychosocial
      impairment. The need for early prevention and intervention - regardless of CUD
      status - was highlighted by the presence of these patterns in adolescence.

PMID- 29173212
TI  - Substitutions between dairy product subgroups and risk of type 2 diabetes: the
      Danish Diet, Cancer and Health cohort.
AB  - The aim of this study was to investigate the associations for specified
      substitutions between different subgroups of dairy products and the risk of type
      2 diabetes. We used data from the Danish Diet, Cancer and Health cohort including
      54 277 men and women aged 50-64 years at baseline. Information regarding intake
      of dairy products was obtained from a validated FFQ, and cases of type 2 diabetes
      were identified through the Danish National Diabetes Register. Cox proportional
      hazards regressions were used to estimate associations. During a median follow-up
      of 15.3 years, 7137 cases were identified. Low-fat yogurt products in place of
      whole-fat yogurt products were associated with a higher rate of type 2 diabetes
      (hazard ratio (HR) 1.17; 95 % CI 1.06, 1.29) per serving/d substituted. Whole-fat
      yogurt products in place of low-fat milk, whole-fat milk or buttermilk were
      associated with a lower rate of type 2 diabetes (HR 0.89; 95 % CI 0.83, 0.96; HR
      0.89; 95 % CI 0.82, 0.96; HR 0.89; 95 % CI 0.81, 0.97; per serving/d substituted,
      respectively). The pattern of associations was similar when intake was expressed
      as kJ/d (kcal/d). These findings suggest that intake of whole-fat yogurt products
      in place of low-fat yogurt products, low-fat milk, whole-fat milk and buttermilk
      are associated with a lower rate of type 2 diabetes.

PMID- 29173213
TI  - Evaluation of reference genes for reverse transcription-quantitative PCR assays
      in organs of zebrafish exposed to glyphosate-based herbicide, Roundup.
AB  - Roundup is a glyphosate-based herbicide (GBH) widely used in agriculture and may
      cause toxic effects in non-target organisms. Model organisms, as zebrafish, and
      analysis of gene expression by reverse transcription-quantitative PCR (RT-qPCR)
      could be used to better understand the Roundup toxicity. A prerequisite for RT
      qPCR is the availability of appropriate reference genes; however, they have not
      been described for Roundup-exposed fish. The aim of this study was to evaluate
      the expression stability of six reference genes (rpl8, beta-act, gapdh, b2m,
      ef1alpha, hprt1) and one expressed repetitive element (hatn10) in organs of males
      (brain, gill, testis) and females (ovary) of zebrafish exposed to Roundup WG at
      three concentrations (0.065, 0.65 and 6.5 mg N-(phosphonomethyl) glycine/l) for 7
      days. Genes were ranked by geNorm, NormFinder, BestKeeper, Delta C t and
      RefFinder, and their best combinations were determined by geNorm and NormFinder
      programs. The two most stable ranked genes were specific to each organ: gill
      (beta-act; rpl8); brain (rpl8; beta-act); testis (ef1alpha; gapdh); and ovary
      (rpl8; hprt1). The cat transcript level was used to evaluate the effect of
      normalization with these reference genes. These are the first suitable reference
      genes described for the analysis of gene expression in organs of Roundup-exposed
      zebrafish, and will allow investigations of the molecular mechanisms of Roundup
      toxicity.

PMID- 29173214
TI  - Appetitive drives for ultra-processed food products and the ability of text
      warnings to counteract consumption predispositions.
AB  - OBJECTIVE: The present study aimed to (i) assess the appetitive drives evoked by
      the visual cues of ultra-processed food and drink products and (ii) investigate
      whether text warnings reduce appetitive drives and consumers' reported intentions
      to eat or drink ultra-processed products. DESIGN: In Study I, a well-established
      psychometric tool was applied to estimate the appetitive drives associated with
      ultra-processed products using sixty-four image representations. Sixteen product
      types with four exemplars of a given product were included. Pictures from the
      International Affective Picture System (IAPS) served as controls. The two
      exemplars of each product type rated as more appetitive were selected for
      investigation in the second study. Study II assessed the impact of textual
      warnings on the appetitive drive towards these thirty-two exemplars. Each
      participant was exposed to two picture exemplars of the same product type
      preceded by a text warning or a control text. After viewing each displayed
      picture, the participants reported their emotional reactions and their intention
      to consume the product. SETTING: Controlled classroom experiments SUBJECTS:
      Undergraduate students (Study I: n 215, 135 women; Study II: n 98, 52 women).
      RESULTS: In Study I, the pictures of ultra-processed products prompted an
      appetitive motivation associated with the products' nutritional content. In Study
      II, text warnings were effective in reducing the intention to consume and the
      appetitive drive evoked by ultra-processed products. CONCLUSIONS: This research
      provides initial evidence favouring the use of text warnings as a public policy
      tool to curb the powerful influence of highly appetitive ultra-processed food
      cues.

PMID- 29173215
TI  - Quantity and species of fish consumed shape breast-milk fatty acid concentrations
      around Lake Victoria, Kenya.
AB  - OBJECTIVE: Long-chain PUFA (LCPUFA) found in breast milk are derived from dietary
      sources and critical for optimal infant development. We examined associations
      between fish consumption and concentrations of LCPUFA and essential n-3 and n-6
      fatty acids in breast milk among mothers living around Lake Victoria. DESIGN: We
      used cross-sectional analyses of associations between recent fish consumption and
      breast-milk fatty acid concentrations. SETTING: The study was conducted around
      Lake Victoria on Mfangano Island, Kenya, where multiple fish species are key
      dietary components and also are widely exported. SUBJECTS: Breast-feeding mothers
      (n 60) provided breast-milk samples, anthropometric measurements and
      questionnaire responses. RESULTS: In the previous 3 d, 97 % of women consumed a
      mean of 178 (sd 111) g fish (~2 servings/3 d). Mean breast-milk concentrations
      included DHA (0.75 % of total fatty acids), EPA (0.16 %), alpha-linolenic acid
      (ALA; 0.54 %), arachidonic acid (AA; 0.44 %) and linoleic acid (LA; 12.7 %).
      Breast-milk DHA concentrations exceeded the global average of 0.32 % in fifty
      nine of sixty samples. We found native cichlids (Cichlidae) and dagaa
      (Rastrineobola argentea) contributed high levels of DHA, EPA and AA to local
      diets. We also found evidence for associations between fish species consumed and
      breast-milk LCPUFA concentrations when controlling for intake of other fish
      species, maternal body mass, maternal age, child age and exclusive breast
      feeding. CONCLUSIONS: The fatty acid composition of breast milk was influenced by
      the fish species consumed. Ensuring access to diverse fish and particularly
      inexpensive, locally available species, may be important for diet quality as well
      as infant growth and development.

PMID- 29173216
TI  - Letter to the Editor: Are older studies lost in database searches for systematic
      reviews?

PMID- 29173217
TI  - Behavioral consequences of mild traumatic brain injury in preschoolers.
AB  - BACKGROUND: Pediatric traumatic brain injury (TBI) is a leading cause of long
      term disability in children and adolescents worldwide. Amongst the wide array of
      consequences known to occur after pediatric TBI, behavioral impairments are among
      the most widespread and may particularly affect children who sustain injury early
      in the course of development. The aim of this study was to investigate the
      presence of internalizing and externalizing behavioral problems 6 months after
      preschool (i.e. 18-60 months old) mild TBI. METHODS: This work is part of a
      prospective, longitudinal cohort study of preschool TBI. Participants (N = 229)
      were recruited to one of three groups: children with mild TBI, typically
      developing children and orthopedic injured (OI) children. Mothers of children in
      all three groups completed the Child Behavior Checklist as a measure of
      behavioral outcomes 6-month post-injury. Demographics, injury-related
      characteristics, level of parental distress, and estimates of pre-injury
      behavioral problems were also documented. RESULTS: The three groups did not
      differ on baseline characteristics (e.g. demographics and pre-injury behavioral
      problems for the mild TBI and OI groups) and level of parental distress. Mothers'
      ratings of internalizing and externalizing behaviors were higher in the mild TBI
      group compared with the two control groups. Pre-injury behavioral problems and
      maternal distress were found to be significant predictors of outcome. CONCLUSION:
      Our results show that even in its mildest form, preschool TBI may cause
      disruption to the immature brain serious enough to result in behavioral changes,
      which persist for several months post-injury.

PMID- 29173218
TI  - Improving the implementation of nutrition guidelines in childcare centres
      improves child dietary intake: findings of a randomised trial of an
      implementation intervention.
AB  - OBJECTIVE: Evidence suggests that improvements to the childcare nutrition
      environment can have a positive impact on child dietary intake. The primary aim
      of the present study was to assess, relative to usual care, the effectiveness of
      a multi-strategy implementation intervention in improving childcare compliance
      with nutrition guidelines. As a secondary aim, the impact on child dietary intake
      was assessed. DESIGN: Parallel-group, randomised controlled trial design. The 6
      month intervention was designed to overcome barriers to implementation of the
      nutrition guidelines that had been identified by applying the theoretical domains
      framework. SETTING: Hunter New England region, New South Wales, Australia.
      SUBJECTS: Forty-five centre-based childcare services. RESULTS: There were no
      differences between groups in the proportion of services providing food servings
      (per child) compliant with nutrition guideline recommendations for all five (5/5)
      food groups at follow-up (i.e. full compliance). Relative to control services,
      intervention services were more likely to be compliant with guidelines (OR; 95 %
      CI) in provision of fruit (10.84; 1.19, 551.20; P=0.0024), meat and meat
      alternatives (8.83; 1.55, -; P=0.023), dairy (8.41; 1.60, 63.62; P=0.006) and
      discretionary foods (17.83; 2.15, 853.73; P=0.002). Children in intervention
      services consumed greater servings (adjusted difference; 95 % CI) of fruit (0.41;
      0.09, 0.73; P=0.014) and vegetables (0.70; 0.33, 1.08; P<0.001). CONCLUSIONS:
      Findings indicate that service-level changes to menus in line with dietary
      guidelines can result in improvements to children's dietary intake. The study
      provides evidence to advance implementation research in the setting as a means of
      enhancing child public health nutrition.

PMID- 29173219
TI  - Multidisciplinary family-centred psychosocial care for patients with CHD:
      consensus recommendations from the AEPC Psychosocial Working Group - ERRATUM.

PMID- 29173221
TI  - Convenience-based food purchase patterns: identification and associations with
      dietary quality, sociodemographic factors and attitudes.
AB  - OBJECTIVE: The present study aimed to derive food purchase patterns considering
      the convenience level of foods. Associations between identified patterns and
      dietary quality were analysed, as well as household characteristics associated
      with the dietary patterns. DESIGN: A Convenience Food Classification Scheme
      (CFCS) was developed. After classifying basic food groups into the CFCS, the
      formed groups were used to apply a factor analysis to identify convenience-based
      food purchase patterns. For these patterns nutrient and energy densities were
      examined. Using regression analysis, associations between the adherence to the
      patterns and household characteristic and attitude variables were analysed.
      SUBJECTS: The study used representative German food purchase data from 2011.
      Approximately 12 million purchases of 13 131 households were recorded in these
      data. RESULTS: Three convenience-based patterns were identified: a low
      convenience, a semi-convenience and a ready-to-eat food pattern. Tighter
      adherence to the semi-convenience pattern was shown to result in the lowest
      nutrient and highest energy densities. Important factors influencing adherence to
      the patterns were household size, presence of children and attitudes. Working
      full-time was negatively associated with adherence to the low-convenience pattern
      and positively with the ready-to-eat pattern. CONCLUSIONS: Convenience foods were
      an important part of households' food baskets which in some cases led to lower
      nutritional quality. Therefore, it is important to offer convenience foods higher
      in nutrient density and lower in energy density. Interventions targeted on
      enhancing cooking skills could be an effective strategy to increase purchases of
      unprocessed foods, which, in turn, could also contribute to an improved diet
      quality.

PMID- 29173220
TI  - Manganese influences the expression of fatty acid synthase and malic enzyme in
      cultured primary chicken hepatocytes.
AB  - Two experiments were designed to investigate the effects of Mn source and
      concentration on the mRNA expression and enzymatic activities of fatty acid
      synthase (FAS) and malic enzyme (ME) in cultured primary broiler hepatocytes. In
      Expt 1, primary broiler hepatocytes were treated with 0 (control), 0.25, 0.50 or
      0.75 mmol/l of Mn as inorganic manganese chloride (MnCl2.4H2O) for 24 and 48 h.
      In Expt 2, primary broiler hepatocytes were incubated with 0 (control), 0.25 or
      0.50 mmol/l of Mn as either manganese chloride or Mn-amino acid chelate for 48 h.
      The mRNA levels and activities of FAS and ME in the hepatocytes were measured in
      Expts 1 and 2. The results in Expt 1 showed that only at 48 h mRNA expression
      levels of FAS and ME in the hepatocytes decreased linearly (P0.33) on any of the
      measured cellular parameters. The results suggested that Mn might reduce cell
      damage and regulate FAS and ME expression at a transcriptional level in primary
      cultured broiler hepatocytes.

PMID- 29173222
TI  - Maternal conjugated linoleic acid modulates TAG metabolism in adult rat
      offspring.
AB  - Conjugated linoleic acid (CLA) might regulate the lipid depots in liver and
      adipose tissue. As there is an association between maternal nutrition, fat depots
      and risk of offspring chronic disease, the aim was to investigate the effect of
      maternal CLA consumption on TAG regulation and some inflammatory parameters in
      adult male rat offspring receiving or not receiving CLA. Female Wistar rats were
      fed control (C) or CLA-supplemented (1 %, w/w) diets during 4 weeks before and
      throughout pregnancy and lactation. After weaning, male offspring of CLA rats
      were fed C or CLA diets (CLA/C and CLA/CLA groups, respectively), whereas C male
      rat offspring were fed a C diet (C/C group) for 9 weeks. Serum TAG levels were
      increased in the CLA/CLA and CLA/C groups, associated with a reduction of
      lipoprotein lipase activity and weights of adipose tissue. The liver TAG levels
      were decreased in the CLA/CLA group, related to a significant reduction of fatty
      acid synthase (FAS), acetyl-CoA carboxylase (ACC) and glucose-6-phosphate
      dehydrogenase enzyme activities, as well as to the mRNA levels of FAS, ACC,
      stearoyl-CoA desaturase-1 and sterol regulatory element-binding protein-1c. Even
      though normal TAG levels were found in the liver of CLA/C rats, a reduction of
      lipogenesis was also observed. Thus, these results demonstrated a programming
      effect of CLA on the lipid metabolic pathways leading to a preventive effect on
      the TAG accretion in adipose tissue and the liver of male rat offspring. This
      knowledge could be important to develop some dietary strategies leading to a
      reduced incidence of obesity and fatty acid liver disease in humans.

PMID- 29173223
TI  - Epidemiology and genetic diversity of human parechoviruses circulating among
      children hospitalised with acute gastroenteritis in Pune, Western India: a 5
      years study.
AB  - Human parechoviruses (HPeVs) are known to cause various clinical manifestations
      including acute gastroenteritis. Although HPeV infections and their genotypes
      have been detected in human patients worldwide, no such reports are available
      from India to ascertain the association of HPeVs in acute gastroenteritis. The
      present study was conducted to determine the clinical features and genetic
      diversity of HPeVs detected in children hospitalised for acute gastroenteritis.
      Stool specimens (n = 979) collected from children aged ?5 years hospitalised for
      acute gastroenteritis in Pune, western India during January 2006-December 2010
      were included. HPeV RNA was detected by reverse transcription-polymerase chain
      reaction (RT-PCR) (5'UTR) followed by genotyping using VP1 gene-based PCR and
      phylogenetic analysis. HPeV was detected in 13.9% (136/979) of the cases, co
      infections with other enteric viruses were found in 43.4%. HPeV was more frequent
      in children ?1 year age with infections reported throughout the year. A total of
      102/136 (75%) HPeV strains were genotyped, which comprised 13 different HPeV
      genotypes. Of these, HPeV1 was the most predominant genotype detected and
      phylogenetically clustered with the Harris strain which is rarely reported. The
      study documents circulation of heterogeneous HPeV genotypes. Two variant strains
      of HPeV4 and 'RGD absent' HPeV5 and 6 strains were also detected. This is the
      first report of HPeV with diversified genotypes identified in acute
      gastroenteritis patients from India.

PMID- 29173224
TI  - Occupational therapy for functional neurological disorders: a scoping review and
      agenda for research.
AB  - Functional neurological disorders (FND)-also called psychogenic, nonorganic,
      conversion, and dissociative disorders-constitute one of the commonest problems
      in neurological practice. An occupational therapist (OT) is commonly involved in
      management, but there is no specific literature or guidance for these
      professionals. Classification now emphasizes the importance of positive diagnosis
      of FND based on physical signs, more than psychological features. Studies of
      mechanism have produced new clinical and neurobiological ways of thinking about
      these disorders. Evidence has emerged to support the use of physiotherapy and
      occupational therapy as part of a multidisciplinary team for functional movement
      disorders (FMD) and psychotherapy for dissociative (nonepileptic) attacks. The
      diagnosis and management of FND has entered a new evidence-based era and deserves
      a standard place in the OT neurological curriculum. We discuss specific
      management areas relevant to occupational therapy and propose a research agenda.

PMID- 29173225
TI  - Preventing Respiratory Viral Transmission in Long-Term Care: Knowledge,
      Attitudes, and Practices of Healthcare Personnel.
AB  - OBJECTIVE To examine knowledge and attitudes about influenza vaccination and
      infection prevention practices among healthcare personnel (HCP) in a long-term
      care (LTC) setting. DESIGN Knowledge, attitudes, and practices (KAP) survey.
      SETTING An LTC facility in St Louis, Missouri. PARTICIPANTS All HCP working at
      the LTC facility were eligible to participate, regardless of department or
      position. Of 170 full- and part-time HCP working at the facility, 73 completed
      the survey, a 42.9% response rate. RESULTS Most HCP agreed that respiratory viral
      infections were serious and that hand hygiene and face mask use were protective.
      However, only 46% could describe the correct transmission-based precautions for
      an influenza patient. Correctly answering infection prevention knowledge
      questions did not vary by years of experience but did vary for HCP with more
      direct patient contact versus less patient contact. Furthermore, 42% of
      respondents reported working while sick, and 56% reported that their coworkers
      did. In addition, 54% reported that facility policies made staying home while ill
      difficult. Some respondents expressed concerns about the safety (22%) and
      effectiveness (27%) of the influenza vaccine, and 28% of respondents stated that
      they would not get the influenza vaccine if it was not required. CONCLUSIONS This
      survey of staff in an LTC facility identified several areas for policy
      improvement, particularly sick leave, as well as potential targets for
      interventions to improve infection prevention knowledge and to address HCP
      concerns about influenza vaccination to improve HCP vaccination rates in LTCs.
      Infect Control Hosp Epidemiol 2017;38:1449-1456.

PMID- 29173226
TI  - Drug addiction and alcoholism as predictors for tuberculosis treatment default in
      Brazil: a prospective cohort study.
AB  - This study aimed to evaluate the risk factors for tuberculosis (TB) treatment
      default in a priority city for disease control in Brazil. A cohort of TB cases
      diagnosed from 2008 to 2009 was followed up from patients' entry into three
      outpatient sites, in Juiz de Fora, Minas Gerais (Brazil), until the recording of
      the outcomes. Drug addiction, alcoholism and treatment site appeared to be
      independently associated with default. Current users of crack as the hardest drug
      (odds ratio (OR) 12.25, 95% confidence interval (CI) 3.04-49.26) were more likely
      to default than other hard drug users (OR 5.67, 95% CI 1.34-24.03), former users
      (OR 4.12, 95% CI 1.11-15.20) and those not known to use drugs (reference group).
      Consumers at high risk of alcoholism (OR 2.94, 95% CI 1.08-7.99) and those
      treated in an outpatient hospital unit (OR 8.22, 95% CI 2.79-24.21%) also were
      more likely to default. Our results establish that substance abuse was
      independently associated with default. National TB programmes might be more
      likely to achieve their control targets if they include interventions aimed at
      improving adherence and cure rates, by diagnosing and treating substance abuse
      concurrently with standard TB therapy.

PMID- 29173227
TI  - Improving nutrition to support healthy ageing: what are the opportunities for
      intervention?
AB  - Alongside declining activity levels, energy needs fall in older age and eating
      less is expected. However, as total food consumption declines, intakes of many
      nutrients are also likely to fall; while energy requirements may be met, other
      nutrient needs may not. Although this highlights the importance of nutrient-dense
      foods and overall diet quality in older age to ensure nutrient intakes are
      sufficient, maintaining or increasing diet quality may be difficult at a time
      when food access and preparation are becoming more challenging, and diets may be
      more monotonous. Poor nutrition, even in developed settings, is common. Older
      malnourished adults are more likely to have poorer health outcomes, longer
      hospital stays and increased mortality. Thus, apart from the evident personal
      costs, the economic burden of disease-related malnutrition is significant, and
      effective preventive strategies to promote good nutrition among older populations
      are needed. In particular, there is a need for wider recognition of malnutrition
      risk among older adults, including implementation of routine screening of
      nutritional status and early diagnosis. Design of future interventions to support
      older community-dwelling adults requires a clear understanding of the personal
      and contextual influences that affect patterns of food choice and consumption,
      including consideration of the importance of social and psychological factors. In
      addition, there are opportunities to intervene earlier in the lifecourse; the
      most effective preventive efforts to promote good nutrition in older age may need
      to start ahead of age-related changes in physiology and function, including
      younger adulthood and at the retirement transition.

PMID- 29173228
TI  - Colistin-Resistant Klebsiella Infections Among Pediatric Oncology and
      Hematopoietic Stem Cell Transplantation Patients in Eastern India.

PMID- 29173229
TI  - Prothymosin alpha expression in the vertebrate testis: a comparative review.
AB  - Prothymosin alpha (PTMA) is a highly acidic, intrinsically disordered protein
      that was first extracted from rat thymus and characterized as an immunogenic
      factor but soon detected in a variety of mammalian tissues. The presence of a
      nuclear localization signal and the adoption of a peculiar random-coil
      conformation are among the reasons behind its interaction with several molecular
      partners, hence at this time PTMA is known to be a very conserved and widely
      expressed molecule, involved in numerous and diverse biological processes. Only
      few studies have tried to weigh its possible involvement in reproduction,
      specifically in male gametogenesis: first reports have suggested that PTMA might
      be associated with the proliferative and early-meiotic phases of mammal
      spermatogenesis. Some years later, a comparative project on vertebrate
      spermatogenesis reported the isolation, for the first time, of prothymosin in a
      non-mammalian species, the amphibian Pelophylax esculentus. PTMA transcript and
      protein are localized in the germinal compartment, from spermatocytes to
      spermatozoa. A congruent pattern has been highlighted in studies on the fish
      Torpedo marmorata and Danio rerio, and in the mammal Rattus norvegicus, in which
      the expression of PTMA has been found in meiotic and post-meiotic germ cells
      inside testicular cysts and tubules. Moreover, its presence has been confirmed in
      rat and human spermatozoa (associated with the acrosome); its retention in the
      apical region of the head after the acrosome reaction revealed a striking
      conservation of the pattern during phylogenesis and suggested a possible role for
      the protein in gametogenesis and in fertilization.

PMID- 29173230
TI  - Water Cultures Are More Sensitive Than Swab Cultures for the Detection of
      Environmental Legionella.
AB  - Water cultures were significantly more sensitive than concurrently collected swab
      cultures (n=2,147 each) in detecting Legionella pneumophila within a Veterans
      Affairs healthcare system. Sensitivity for water versus swab cultures was 90%
      versus 30% overall, 83% versus 48% during a nosocomial Legionnaires' disease
      outbreak, and 93% versus 22% post outbreak. Infect Control Hosp Epidemiol
      2018;39:108-110.

PMID- 29173231
TI  - Association between overweight/obesity and eating habits while watching
      television among primary-school children in the city of Shiraz, Iran.
AB  - OBJECTIVE: It has been reported that television (TV) viewing is associated with
      childhood obesity in Western countries. The present study aimed to investigate
      the relationship between obesity and eating habits while watching TV among
      primary-school children in the Middle East. DESIGN: Cross-sectional. SETTING:
      Children were recruited from primary schools of four educational districts in
      Shiraz, Iran. Anthropometric indices of mass (kg) and height (m) were measured,
      and BMI (percentile) was calculated. Demographic characteristics, TV viewing
      behaviours and physical activity data were collected from parents during face-to
      face interviews and a 3d dietary record was completed. Subject Children (n 607)
      aged 6-10 years. RESULTS: Mean (sd) age of children was 8.16 (1.37) years, of
      whom 9.1 and 8.4 % were overweight and obese, respectively. Children who spent
      >=2 h watching TV on weekdays (OR=1.99; 95 % CI 1.09, 3.60) and weekend days
      (OR=1.86; 95 % CI 1.01, 3.43) had higher odds of being obese, even after
      adjusting for physical activity. Children who ate breakfast while watching TV had
      higher odds of being overweight v. those who did not watch TV while eating
      breakfast (OR=2.70; 95 % CI 1.02, 7.60). There were no associations between TV
      viewing during other meals (lunch and dinner) and overweight/obesity.
      CONCLUSIONS: TV viewing for >=2 h daily increases the risk of being obese in
      Iranian children aged 6-10 years, independent of physical activity. Further,
      breakfast consumption while watching TV may increase the risk of
      overweight/obesity, independent of total TV viewing time.

PMID- 29173232
TI  - DO IN UTERO SHOCKS HAVE ADVERSE EFFECTS ON CHILD HEALTH OUTCOMES AND CAN WELFARE
      SCHEMES AMELIORATE SUCH EFFECTS? EVIDENCE FROM ANDHRA PRADESH, INDIA.
AB  - This study aimed to assess whether shocks experienced by children in the mother's
      womb can have an adverse effect on their future health, and whether these effects
      can be ameliorated by government welfare schemes. Data were taken from three
      phases of the Young Lives Survey carried out in the Indian state of Andhra
      Pradesh in 2002, 2007 and 2009-2010. Different types of in utero shock were
      distinguished from the data. Using ordinary least squares (OLS) estimation, it
      was observed that multiple in utero shocks reduced children's weight-for-age and
      height-for-age z-scores by 0.07-0.08 and 0.08-0.15 units respectively. The roles
      of two Indian government welfare schemes - the Midday Meal Scheme (MDMS) and the
      National Rural Employment Guarantee Scheme (NREGS) - in mitigating the adverse
      effects of in utero shocks were examined. While the effect of the MDMS was
      statistically insignificant, that of the NREGS was significant. Although not
      designed to protect child health, the NREGS has been playing a more effective
      role than the MDMS in acting as a buffer against the damaging effects of in utero
      shocks on child health. The study points to the need for greater co-ordination
      between the two welfare schemes.

PMID- 29173233
TI  - Fact or fiction: reducing the proportion and impact of false positives.
AB  - False positive findings in science are inevitable, but are they particularly
      common in psychology and psychiatry? The evidence that we review suggests that
      while not restricted to our field, the problem is acute. We describe the concept
      of researcher 'degrees-of-freedom' to explain how many false-positive findings
      arise, and how the various strategies of registration, pre-specification, and
      reporting standards that are being adopted both reduce and make these visible. We
      review possible benefits and harms of proposed statistical solutions, from
      tougher requirements for significance, to Bayesian and machine learning
      approaches to analysis. Finally we consider the organisation and methods for
      replication and systematic review in psychology and psychiatry.

PMID- 29173234
TI  - Dietary alpha-lactalbumin induced fatty liver by enhancing nuclear liver X
      receptor alphabeta/sterol regulatory element-binding protein-1c/PPARgamma
      expression and minimising PPARalpha/carnitine palmitoyltransferase-1 expression
      and AMP-activated protein kinase alpha phosphorylation associated with
      atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c
      mice.
AB  - The effect and the role played by dietary alpha-lactalbumin (alpha-LAC) on
      hepatic fat metabolism are yet to be fully elucidated. We reported previously
      that alpha-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim
      of the present study was to investigate if this atherogenic effect could be due
      to a possible alpha-LAC-induced hepatic steatosis. We examine the ability of
      dietary alpha-LAC to induce liver steatosis, identifying the molecular mechanisms
      underlying hepatic lipid metabolism in association with the lipid profile,
      peripheral insulin resistance (IR) and changes in the hepatic oxidative
      environment. Male Balb/c mice (n 6) were fed with diets containing either chow or
      14 % alpha-LAC for 4 weeks. The alpha-LAC-fed mice developed abdominal adiposity
      and IR. Moderate liver steatosis with increased TAG and NEFA contents was
      correlated with atherogenic dyslipidaemia. There was increased nuclear expression
      of liver X receptor alphabeta (LXRalphabeta), sterol regulatory element-binding
      protein-1c (SREBP-1c) and PPARgamma transcription factors and of the cytosolic
      enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the
      hepatic de novo lipogenesis. The opposite was found for the nuclear receptor
      PPARalpha and the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1),
      leading to reduced fatty acid beta-oxidation (FAO). These changes were associated
      with a significant decrease in both p-Thr172-AMP-activated protein kinase alpha
      (AMPKalpha) (inactivation) and p-Ser79-ACC1 (activation) and with a more
      oxidative liver environment increasing lipid peroxidation and protein oxidation
      and reducing GSH:GSSG ratio in the alpha-LAC-fed mice. In conclusion, 4 weeks of
      14 % alpha-LAC feeding induced liver steatosis associated with atherogenic
      dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRalphabeta/SREBP
      1c/PPARgamma expression and diminishing PPARalpha/CPT-1 expression and AMPKalpha
      phosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c
      mice.

PMID- 29173235
TI  - Delaying meiotic resumption during transportation of bovine cumulus-oocyte
      complexes: effects on development, apoptosis and caspases activity of in vitro
      produced embryos.
AB  - This study examined the effects of meiosis inhibition during bovine oocyte
      transportation on developmental competence and quality of produced embryos. The
      transportation medium was supplemented with: 100 MUM butyrolactone I (BL), 500
      MUM IBMX + 100 MUM forskolin (mSPOM), 100 MUM milrinone (MR) or follicular fluid
      (bFF), and was carried out in a portable incubator for 6 h. Next, oocytes were in
      vitro matured (IVM) for 18 h, without the meiotic inhibitors, with the exception
      of mSPOM group, in which was added 20 MUM cilostamide. The three control groups
      were IVM with 10% fetal calf serum (FCS) (Control Lab FCS) or 0.6% bovine serum
      albumin (BSA) (Control Lab BSA) in a CO2 in air incubator or in the portable
      incubator with 0.6% BSA (Control Transp BSA). Higher cleavage rates (P 0.05) to
      the other groups (23.6 +/- 3.3% to 28.8 +/- 2.7%). The total number of
      blastomeres was higher (P 0.05) from bFF (67.7 +/- 4.2). No differences (P >
      0.05) were found in apoptosis by the activity of caspases (139.0 +/- 3.2 to 152.4
      +/- 6.5, expressed in fluorescence intensity) as well as the percentage of TUNEL
      positive cells (12.3 +/- 2.0% to 15.7 +/- 1.7%). In conclusion, the
      transportation of oocytes over 6 h with BL, mSPOM or bFF enabled the acquisition
      of developmental competence at similar rates to the Control Lab FCS group.

PMID- 29173236
TI  - Attributable Cost of Clostridium difficile Infection in Pediatric Patients.
AB  - OBJECTIVES The attributable cost of Clostridium difficile infection (CDI) in
      children is unknown. We sought to determine a national estimate of attributable
      cost and length of stay (LOS) of CDI occurring during hospitalization in
      children. DESIGN AND METHODS We analyzed discharge records of patients between 2
      and 18 years of age from the Agency for Healthcare Research and Quality (AHRQ)
      Kids' Inpatient Database. We created a logistic regression model to predict CDI
      during hospitalization based on demographic and clinical characteristics.
      Predicted probabilities from the logistic regression model were then used as
      propensity scores to match 1:2 CDI to non-CDI cases. Charges were converted to
      costs and compared between patients with CDI and propensity-score-matched
      controls. In a sensitivity analysis, we adjusted for LOS as a confounder by
      including it in both the propensity score and a generalized linear model
      predicting cost. RESULTS We identified 8,527 pediatric hospitalizations (0.53%)
      with a diagnosis of CDI and 1,597,513 discharges without CDI. In our matched
      cohorts, the attributable cost of CDI occurring during a hospitalization ranged
      from $1,917 to $8,317, depending on whether model was adjusted for LOS. When not
      adjusting for LOS, CDI-associated hospitalizations cost 1.6 times more than non
      CDI associated hospitalizations. Attributable LOS of CDI was approximately 4
      days. CONCLUSIONS Clostridium difficile infection in hospitalized children is
      associated with an economic burden similar to adult estimates. This finding
      supports a continued focus on preventing CDI in children as a priority. Pediatric
      CDI cost analyses should account for LOS as an important confounder of cost.
      Infect Control Hosp Epidemiol 2017;38:1472-1477.

PMID- 29173237
TI  - Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and
      metabolome in mice.
AB  - n-3 PUFA are lipids that play crucial roles in immune-regulation, cardio
      protection and neurodevelopment. However, little is known about the role that
      these essential dietary fats play in modulating caecal microbiota composition and
      the subsequent production of functional metabolites. To investigate this, female
      C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented
      (n3+) or n-3 deficient (n3-)) during gestation, following which their male
      offspring were continued on the same diets for 12 weeks. Caecal content of
      mothers and offspring were collected for 16S sequencing and metabolic
      phenotyping. n3- male offspring displayed significantly less % fat mass than n3+
      and CON. n-3 Status also induced a number of changes to gut microbiota
      composition such that n3- offspring had greater abundance of Tenericutes,
      Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in
      caecal metabolites involved in energy metabolism in n3+ including alpha
      ketoglutaric acid, malic acid and fumaric acid. n3- animals displayed
      significantly reduced acetate, butyrate and total caecal SCFA production. These
      results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis
      whereby n-3 deficiency may induce a state of disturbance. Further studies are
      warranted to examine whether these microbial and metabolic disturbances are
      causally related to changes in metabolic health outcomes.

PMID- 29173238
TI  - Toward a Two-Dimensional Model of Social Cognition in Clinical Neuropsychology: A
      Systematic Review of Factor Structure Studies.
AB  - OBJECTIVE: Social cognition has received growing interest in many conditions in
      recent years. However, this construct still suffers from a considerable lack of
      consensus, especially regarding the dimensions to be studied and the resulting
      methodology of clinical assessment. Our review aims to clarify the
      distinctiveness of the dimensions of social cognition. METHOD: Based on Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements, a
      systematic review was conducted to explore the factor structure of social
      cognition in the adult general and clinical populations. RESULTS: The initial
      search provided 441 articles published between January 1982 and March 2017.
      Eleven studies were included, all conducted in psychiatric populations and/or
      healthy participants. Most studies were in favor of a two-factor solution. Four
      studies drew a distinction between low-level (e.g., facial emotion/prosody
      recognition) and high-level (e.g., theory of mind) information processing. Four
      others reported a distinction between affective (e.g., facial emotion/prosody
      recognition) and cognitive (e.g., false beliefs) information processing.
      Interestingly, attributional style was frequently reported as an additional
      separate factor of social cognition. CONCLUSIONS: Results of factor analyses add
      further support for the relevance of models differentiating level of information
      processing (low- vs. high-level) from nature of processed information (affective
      vs. cognitive). These results add to a significant body of empirical evidence
      from developmental, clinical research and neuroimaging studies. We argue the
      relevance of integrating low- versus high-level processing with affective and
      cognitive processing in a two-dimensional model of social cognition that would be
      useful for future research and clinical practice. (JINS, 2018, 24, 391-404).

PMID- 29173239
TI  - First phylogenetic analysis of dengue virus serotype 4 circulating in Espirito
      Santo state, Brazil, in 2013 and 2014.
AB  - The purpose of the present study was to reconstruct the phylogeny of dengue virus
      serotype 4 (DENV-4) that was circulating in Espirito Santo state, Brazil, in 2013
      and 2014, and to discuss the epidemiological implications associated with this
      evolutionary hypothesis. Partial envelope gene of eight DENV-4 samples from
      Espirito Santo state were sequenced and aligned with 72 worldwide DENV-4
      reference sequences from GenBank. A phylogenetic tree was reconstructed through
      Bayesian Inference and the Time of the Most Recent Common Ancestor was estimated.
      The study detected the circulation of DENV-4 genotype II in Espirito Santo state,
      which was closely related to strains from the states of Mato Grosso collected in
      2012 and of Sao Paulo sampled in 2015. This cluster emerged around 2011,
      approximately 4 years after the entry of the genotype II in Brazil through its
      northern states, possibly imported from Venezuela and Colombia. This is so far
      the first phylogenetic study of the DENV-4 circulating in Espirito Santo state
      and shows the importance of an internal route of dengue viral circulation in
      Brazil to the introduction of the virus into this state.

PMID- 29173240
TI  - Overweight negatively affects outcome of superovulation treatment in female mice.
AB  - Superovulatory response is characterized by a high degree of variability and
      unpredictability. The aim of the present experimental study was to examine
      whether the amount of maternal body fat can influence the efficiency of ovarian
      stimulation with gonadotropins. Female mice of two body condition types, normal
      and obese, produced in a standardized two-generation model, were subjected to
      ovarian stimulation using eCG and hCG followed by natural mating. Produced ova
      and embryos were recovered on day 1 and day 4 of pregnancy respectively, and
      several quantitative, qualitative and developmental parameters were evaluated in
      them. The overall response of mouse females with normal and elevated amounts of
      body fat to superovulation was similar: They produced almost the same numbers of
      ova and embryos on average. Conversely, a higher number of immature oocytes, non
      fertilized mature oocytes and lower-stage zygotes were collected from fat
      females. In both groups, the majority of fertilized oocytes was able to cleave
      and reach the higher stages of development. However, in the group of fat mice, a
      lower number of blastocysts was collected, and these blastocysts showed increased
      incidence of apoptotic cell death. In conclusion, although the response of normal
      and fat mice to superovulatory treatment was similar, the quality and
      developmental capacities of produced ova were lower in the group of fat donors.

PMID- 29173241
TI  - X-Ray Excited Optical Luminescence and Portable Electron Probe Microanalyzer
      Cathodoluminescence (EPMA-CL) Analyzers for On-Line and On-Site Analysis of
      Nonmetallic Inclusions in Steel.
AB  - The potential of the application of an X-ray excited optical luminescence (XEOL)
      analyzer and portable analyzers, composed of a cathodoluminescence (CL)
      spectrometer and electron probe microanalyzer (EPMA), to the on-line and on-site
      analysis of nonmetallic inclusions in steel is investigated as the first step
      leading to their practical use. MgAl2O4 spinel and Al2O3 particles were
      identified by capturing the luminescence as a result of irradiating X-rays in air
      on a model sample containing MgAl2O4 spinel and Al2O3 particles in the size range
      from 20 to 50 MUm. We were able to identify the MgAl2O4 spinel and Al2O3
      particles in the same sample using the portable CL spectrometer. In both cases,
      not all of the particles in the sample were identified because the luminescence
      intensities of the smaller Al2O3 in particular were too low to detect. These
      problems could be solved by using an X-ray tube with a higher power and
      increasing the beam current of the portable CL spectrometer. The portable EPMA
      distinguished between the MgAl2O4 spinel and Al2O3 particles whose luminescent
      colors were detected using the portable CL spectrometer. Therefore, XEOL analysis
      has potential for the on-line analysis of nonmetallic inclusions in steel if we
      have information on the luminescence colors of the nonmetallic inclusions. In
      addition, a portable EPMA-CL analyzer would be able to perform on-site analysis
      of nonmetallic inclusions in steel.

PMID- 29173243
TI  - Brain correlates of recognition of communicative interactions from biological
      motion in schizophrenia.
AB  - BACKGROUND: Recognition of communicative interactions is a complex social
      cognitive ability which is associated with a specific neural activity in healthy
      individuals. However, neural correlates of communicative interaction processing
      from whole-body motion have not been known in patients with schizophrenia (SCZ).
      Therefore, the current study aims to examine the neural activity associated with
      recognition of communicative interactions in SCZ by using displays of the dyadic
      interactions downgraded to minimalistic point-light presentations. METHODS:
      Twenty-six healthy controls (HC) and 25 SCZ were asked to judge whether two
      agents presented only by point-light displays were communicating or acting
      independently. Task-related activity and functional connectivity of brain
      structures were examined with General Linear Model and Generalized
      Psychophysiological Interaction approach, respectively. RESULTS: HC were
      significantly more efficient in recognizing each type of action than SCZ. At the
      neural level, the activity of the right posterior superior temporal sulcus (pSTS)
      was observed to be higher in HC compared with SCZ for communicative v. individual
      action processing. Importantly, increased connectivity of the right pSTS with
      structures associated with mentalizing (left pSTS) and mirroring networks (left
      frontal areas) was observed in HC, but not in SCZ, during the presentation of
      social interactions. CONCLUSION: Under-recruitment of the right pSTS, a structure
      known to have a pivotal role in social processing, may also be of importance for
      higher-order social cognitive deficits in SCZ. Furthermore, decreased task
      related connectivity of the right pSTS may result in reduced use of additional
      sources of information (for instance motor resonance signals) during social
      cognitive processing in schizophrenia.

PMID- 29173242
TI  - Evidence of multiple intraspecific transmission routes for Leptospira acquisition
      in Norway rats (Rattus norvegicus).
AB  - Infectious diseases frequently have multiple potential routes of intraspecific
      transmission of pathogens within wildlife and other populations. For pathogens
      causing zoonotic diseases, knowing whether these transmission routes occur in the
      wild and their relative importance, is critical for understanding maintenance,
      improving control measures and ultimately preventing human disease. The Norway
      rat (Rattus norvegicus) is the primary reservoir of leptospirosis in the urban
      slums of Salvador, Brazil. There is biological evidence for potentially three
      different transmission routes of leptospire infection occurring in the rodent
      population. Using newly obtained prevalence data from rodents trapped at an urban
      slum field site, we present changes in cumulative risk of infection in relation
      to age-dependent transmission routes to infer which intra-specific transmission
      routes occur in the wild. We found that a significant proportion of animals leave
      the nest with infection and that the risk of infection increases throughout the
      lifetime of Norway rats. We did not observe a significant effect of sexual
      maturity on the risk of infection. In conclusion, our results suggest that
      vertical and environmental transmission of leptospirosis both occur in wild
      populations of Norway rats.

PMID- 29173244
TI  - Socio-economic variations in the mental health treatment gap for people with
      anxiety, mood, and substance use disorders: results from the WHO World Mental
      Health (WMH) surveys.
AB  - BACKGROUND: The treatment gap between the number of people with mental disorders
      and the number treated represents a major public health challenge. We examine
      this gap by socio-economic status (SES; indicated by family income and respondent
      education) and service sector in a cross-national analysis of community
      epidemiological survey data. METHODS: Data come from 16 753 respondents with 12
      month DSM-IV disorders from community surveys in 25 countries in the WHO World
      Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and
      treatment of these disorders were assessed with the WHO Composite International
      Diagnostic Interview (CIDI). RESULTS: Only 13.7% of 12-month DSM-IV/CIDI cases in
      lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8%
      in high-income countries received treatment. Highest-SES respondents were
      somewhat more likely to receive treatment, but this was true mostly for specialty
      mental health treatment, where the association was positive with education
      (highest treatment among respondents with the highest education and a weak
      association of education with treatment among other respondents) but non
      monotonic with income (somewhat lower treatment rates among middle-income
      respondents and equivalent among those with high and low incomes). CONCLUSIONS:
      The modest, but nonetheless stronger, an association of education than income
      with treatment raises questions about a financial barriers interpretation of the
      inverse association of SES with treatment, although future within-country
      analyses that consider contextual factors might document other important
      specifications. While beyond the scope of this report, such an expanded analysis
      could have important implications for designing interventions aimed at increasing
      mental disorder treatment among socio-economically disadvantaged people.

PMID- 29173245
TI  - Toward understanding chronic kidney disease in African Americans.

PMID- 29173246
TI  - Obesity counseling: Beyond 'eat less, move more'.

PMID- 29173247
TI  - Can effective obesity counseling fit into the 20-minute appointment?

PMID- 29173248
TI  - 2017 Update in perioperative medicine: 6 questions answered.
AB  - The authors performed a MEDLINE search to identify articles published between
      January 2016 and April 2017 that had significant impact on perioperative care.
      They identified 6 topics for discussion.

PMID- 29173249
TI  - ADHD: Overdiagnosed and overtreated, or misdiagnosed and mistreated?
AB  - In today's changing medical climate, physicians need to treat attention
      deficit/hyperactivity disorder (ADHD) better and more cost-effectively. The
      authors review recommendations supported by recent research and offer simple
      practices that integrate medicine and behavioral health for patients with ADHD.

PMID- 29173250
TI  - Abdominal pain and bloody diarrhea in a 32-year-old woman.

PMID- 29173251
TI  - Fever after recent travel.

PMID- 29173252
TI  - Chronic kidney disease in African Americans: Puzzle pieces are falling into
      place.
AB  - Recent decades have seen great advances in the understanding of chronic kidney
      disease, spurred by standardizing disease definitions and large-scale patient
      surveillance. African Americans are disproportionately affected by the disease,
      and recently discovered genetic variants in APOL1 that protect against sleeping
      sickness in Africa provide an important explanation for the increased burden.
      Studies are now under way to determine if genetic testing of African American
      transplant donors and recipients is advisable.

PMID- 29173253
TI  - Iliopsoas abscess.

PMID- 29173255
TI  - Dr. Louis Kristal at 100: witness to the evolution of surgery in Canada.

PMID- 29173254
TI  - Scapular rash and endocrine neoplasia.

PMID- 29173256
TI  - Le Dr Louis Kristal a 100 ans : temoin de l'evolution de la chirurgie au Canada.

PMID- 29173257
TI  - Training Canadian surgeons in oncoplastic breast surgery: Where do we stand?
AB  - SUMMARY: Breast-conserving surgery with adjuvant radiation therapy is widely
      accepted as a universal standard of care for women with early-stage breast
      cancer. Oncoplastic breast-conserving surgery (OPS) techniques have emerged in
      recent years, facilitating the achievement of better cosmetic results while
      adhering to good oncological principles. Compared with the rest of the
      international community, Canada has been fairly slow in its clinical uptake of
      OPS. This commentary discusses how Canada can increase its capacity for OPS.

PMID- 29173258
TI  - The 1917 Halifax Explosion: the first coordinated local civilian medical response
      to disaster in Canada.
AB  - SUMMARY: The 1917 Halifax Explosion was an unfortunate but predictable tragedy,
      given the sea traffic and munitions cargo, resulting in sudden large-scale damage
      and catastrophic injuries, with 1950 dead and 8000 injured. Although generous
      support was received from the United States, the bulk of the medical work was
      undertaken using local resources through an immediate, massive, centrally
      coordinated medical response. The incredible care provided 100 years ago by these
      Canadian physicians, nurses and students is often forgotten, but deserves
      attention. The local medical response to the 1917 disaster is an early example of
      coordinated mass casualty relief, the first in Canada, and remains relevant to
      modern disaster preparedness planning. This commentary has an appendix, available
      at canjsurg.ca/016317-a1.

PMID- 29173259
TI  - Optimizing associated liver partition and portal vein ligation for staged
      hepatectomy outcomes: Surgical experience or appropriate patient selection?
AB  - BACKGROUND: Early reports of associated liver partition and portal vein ligation
      for staged hepatectomy (ALPPS) outcomes have been suboptimal. The literature has
      confirmed that learning curves influence surgical outcomes. We have 54 months of
      continuous experience performing ALPPS with strict selection criteria. This study
      aimed to evaluate the impact of the learning curve on ALPPS outcomes. METHODS: We
      retrospectively compared patients who underwent ALPPS between April 2012 and
      March 2016. Patients were grouped into 2 24-month (early and late) periods. All
      candidates had a high tumour load requiring staged hepatectomy after chemotherapy
      response, a predicted future liver remnant (FLR) less than 30% and good
      performance status. RESULTS: Thirty-three patients underwent ALPPS during the
      study period: 16 in the early group (median age 65 yr, mean body mass index [BMI]
      27) and 17 in the late group (median age 60 yr, mean BMI 25). Bilobar disease was
      comparable in both groups (94% v. 88%, p > 0.99). Duration of surgery was not
      statistically different. Intraoperative blood loss and need for transfusion were
      significantly lower in the late group (200 +/- 109 mL v. 100 +/- 43 mL, p <
      0.05). The late group had a higher proportion of monosegment ALPPS (4:1). There
      were no deaths within 90 days in either cohort. Rates of postoperative
      complications were not statistically significant between groups. The R0 resection
      rate was similar. The entire 1-year disease-free and overall survival were 52%
      and 84%, respectively. CONCLUSION: Excellent results can be obtained in
      innovative complex surgery with careful patient selection and good technical
      skills. Additionally, the learning curve brought confidence to perform more
      complex procedures while maintaining good outcomes.

PMID- 29173261
TI  - The importance of cognitive map placement in bile duct injuries.
AB  - SUMMARY: Bile duct injuries often occur because of surgeon spatial
      disorientation. The psychological concept of cognitive map misplacement is a
      useful explanation of how this disorientation and injury occurs. Surgeons may
      find that using a "bile duct time out" is a helpful way to orient. Based on the
      mnemonic B-SAFE, they can use 5 subhepatic landmarks (B, bile duct; S, sulcus of
      Rouviere; A, hepatic artery; F, umbilical fissure; E, enteric/duodenum) to
      correctly place their cognitive map.

PMID- 29173260
TI  - Transanal minimally invasive surgery for benign large rectal polyps and early
      malignant rectal cancers: experience and outcomes from the first Canadian centre
      to adopt the technique.
AB  - BACKGROUND: Transanal minimally invasive surgery (TAMIS) has emerged as a
      relatively new technique in treating early cancer and benign lesion of the
      rectum. The technique is likely to be widely adopted, surpassing other comparable
      techniques owing to its simple setup and cost-effectiveness. We assessed the
      outcomes of TAMIS at our centre. METHODS: We retrospectively reviewed
      prospectively collected data on 50 patients who underwent TAMIS for benign,
      malignant T1 or T2 cancers that were unfit for radical surgery over a 4-year
      period. Outcomes, including 30-day complications and recurrence, as well as our
      ability to implement and integrate this technique at our centre were assessed.
      RESULTS: All 50 TAMIS procedures were successful. The average lesion was 7 cm
      from the anal verge, the average tumour size was 2.5 cm, the average duration of
      surgery was 73 minutes, the average length of stay was 1.1 days, and the margin
      negativity was 84%. Major indications in our series included 25 lesions that were
      too large for endoscopic resection, 14 early cancers or high-grade dysplasia, 10
      margin checks postpolypectomy, 6 cases of recurrent polyposis, and 4 medically
      unfit patients. There were no deaths. The rate of short-term complications,
      including rectal bleeding, reoperation and urinary retention, was 16%. The rate
      of long-term complications, including anal incontinence and stenosis, was 4%.
      Benign and malignant recurrence rates were 2% and 6%, respectively. Overall long
      term requirement for invasive procedures, low anterior resection or
      abdominoperineal resection, was 12%. CONCLUSION: To our knowledge, this is the
      first Canadian study showing TAMIS to be an efficient and safe procedure for the
      treatment of well-selected patients with rectal lesions. Outcomes from our centre
      are comparable with those found in the literature.

PMID- 29173263
TI  - Response to: Attitudes and factors contributing to attrition in Canadian surgical
      specialty residency programs.

PMID- 29173262
TI  - Users' guide to the surgical literature: how to assess a noninferiority trial.
AB  - SUMMARY: A well-planned randomized controlled trial (RCT) is the most optimal
      study design to determine if a novel surgical intervention is any different than
      a prevailing one. Traditionally, when we want to show that a new surgical
      intervention is superior to a standard one, we analyze data from an RCT to see if
      the null hypothesis of "no difference" can be rejected (i.e., the 2 surgical
      interventions have the same effect). A noninferiority RCT design seeks to
      determine whether a new intervention is not worse than a prevailing (standard)
      one within an acceptable margin of risk or benefit, referred to as the
      "noninferiority margin." In the last decade, we have observed an increase in the
      publication of noninferiority RCTs. This article explores this type of study
      design and discusses the tools that can be used to appraise such a study.

PMID- 29173264
TI  - Author response.

PMID- 29173265
TI  - Evaluation of the influence of student-led surgery interest groups: a pan
      Canadian survey.

PMID- 29173266
TI  - Case: Testicular oligometastasis from prostate cancer - Report of rare isolated
      recurrence after radiotherapy and intermittent androgen-deprivation therapy.

PMID- 29173267
TI  - Treatment effectiveness in interstitial cystitis/bladder pain syndrome: Do
      patient perceptions align with efficacy-based guidelines?
AB  - INTRODUCTION: We sought to determine if patients' perceptions of success or
      failure of interstitial cystitis/bladder pain syndrome (IC/BPS) therapies
      proposed in treatment guidelines align with the evidence from available clinical
      trial treatment data. METHODS: A total of 1628 adult females with a self-reported
      diagnosis of IC completed a web-based survey in which patients described their
      perceived outcomes with the therapies they were exposed to. Previously published
      literature, used in part to develop IC/BPS guidelines, provided the clinical
      trial data outcomes. Patient-reported outcomes were compared to available
      clinical trial outcomes and published treatment guidelines. RESULTS: Based on
      patient perceived outcomes (benefit:risk ratio), the most effective treatments
      were opioids, phenazopyridine, and alkalizing agents, with amitriptyline and
      antihistamines reported as moderately effective. The only surgical procedure with
      any effectiveness was electrocautery of Hunner's lesions. In order of efficacy
      reported in the literature, the therapies for IC/BPS with predicted superior
      outcomes should be: cyclosporine A, amitriptyline, hyperbaric oxygen, pentosan
      polysulfate plus subcutaneous heparin, botulinum toxin A plus hydrodistension,
      and L-arginine. While some of the guideline recommendations aligned with patient
      reported effectiveness data, there was a general disconnect between guidelines
      and effectiveness reported in clinical practice. CONCLUSIONS: There is a
      disconnect between real-world patient perceived effectiveness of IC/BPS
      treatments compared to the efficacy reported from clinical trial data and
      subsequent guidelines developed from this efficacy data. Optimal therapy must
      include the best evidence from clinical research, but should also include real
      life clinical practice implementation and effectiveness.

PMID- 29173268
TI  - Case: Pediatric paratesticular soft tissue perineurinoma - A rare entity.

PMID- 29173269
TI  - Transrectal ultrasound-guided prostate biopsies vs. magnetic resonance imaging
      ultrasound fusion targeted biopsies: Who are the best candidates?
AB  - INTRODUCTION: The aim of this study was to compare the results of ultrasound
      guided prostate biopsies (US-PB) and magnetic resonance imaging-ultrasound fusion
      biopsies (MRI-PB) in two contemporary cohorts and to describe the parameters
      orienting the choice of technique. METHODS: Two contemporary cohorts of patients
      undergoing US-PB or MR-PB using the Urostation(r) (Koelis, Grenoble, France)
      between November 2010 and July 2015 were analyzed retrospectively. Patients with
      metastatic cancer or recurrence after treatment, saturation biopsies, and US-PB
      performed after a negative MRI were excluded. Comparison of populations, biopsy
      results, and clinical and biological parameters guiding the choice of technique
      were studied on multivariate analysis (logistic regression) taking into account
      the following confounding factors: age, prostate-specific antigen (PSA) rate,
      prostatic volume, number of previous biopsies, and abnormal digital rectal
      examination. RESULTS: One hundred fourteen patients were included in the US-PB
      group and 118 in the MR-PB group. Prostate cancer was diagnosed among 65 patients
      in the US-PB group (detection rate 57.0%) and 70 patients in the MR-PB group
      (detection rate 59.3%) (odds ratio [OR] 3.00; 95% confidence interval [CI] 1.52
      6.17; p=0.002). Among the cancers diagnosed in the MR-PB group, 21 were diagnosed
      by the two targeted biopsy cores only (15.5%). Patients undergoing MR-PB were
      significantly younger (p=0.0005), with a higher number of previous biopsy
      sessions (p<10-7) and larger prostate volume (p=0.001). PSA rate alone (p=0.23)
      and digital rectal examination (p=0.48) did not significantly interfere with the
      choice of a technique. CONCLUSIONS: Younger patients with larger prostates and
      prior negative biopsy were more likely to be offered the MR-PB technique. On
      multivariate analysis, the detection rate was higher in the MR-PB group.

PMID- 29173270
TI  - Clinical outcomes of the sequential use of pazopanib followed by everolimus for
      the treatment of metastatic renal cell carcinoma: A multicentre study in Korea.
AB  - INTRODUCTION: The aim of this study was to investigate the real-world clinical
      outcomes of first-line pazopanib and second-line everolimus in Korean patients
      with metastatic renal cell carcinoma (mRCC). METHODS: Data of patients who had
      mRCC with clear-cell component between 2001 and 2015 at multiple institutions
      were collected retrospectively. To be included in the analysis, patients had to
      meet the following criteria: age >=18 years; received first-line targeted therapy
      with pazopanib; and received second-line targeted therapy with everolimus. The
      primary outcomes included overall survival (OS), progression-free survival (PFS),
      and adverse events (AEs). RESULT: A total of 36 patients were included in the
      analysis. The median followup period was 33.5 months (range 17-49.5). The median
      PFS was eight months (95% confidence interval [CI] 6.4-9.6) after treatment with
      pazopanib and three months (95% CI 1.9-4.1) with everolimus. The median OS was 27
      months (95% CI 16.6-37.4). The median treatment duration was seven months (range
      4.3-10.8) after treatment with pazopanib and 3.5 months (range 3-4) with
      everolimus. Multivariate analysis revealed that the Heng risk criteria were
      independently associated with OS (p<0.001). Almost every patient experienced some
      form of AE, the majority of which were mostly mild or moderate in severity. The
      most common AEs were diarrhea (50%), hypertension (44.4%), and fatigue (41.7%)
      after treatment with pazopanib, and anemia (47.2%), stomatitis (41.7%), and
      fatigue (38.9%) with everolimus. CONCLUSIONS: The outcomes for the patients
      treated with pazopanib followed by everolimus in Korea as observed by us were
      consistent with those reported by previous studies. The Heng risk criteria were
      significantly associated with the prognosis of patients with mRCC. AEs were
      mainly mild to moderate and readily managed.

PMID- 29173271
TI  - Case: Spontaneous bladder rupture presenting as sudden-onset abdominal pain in a
      child after many years in remission from bladder rhabdomyosarcoma.

PMID- 29173272
TI  - Case: Bacillus Calmette-Guerin (BCG)-induced Reiter syndrome with an attempt at
      repeat BCG induction.

PMID- 29173273
TI  - Incidence of bleeding in children undergoing circumcision with ketorolac
      administration.
AB  - INTRODUCTION: Circumcision is the most common surgical procedure performed by
      pediatric urologists. Ketorolac has been shown to have an efficacy similar to
      morphine in multimodal analgesic regimens without the commonly associated adverse
      effects. Concerns with perioperative bleeding limit the use of ketorolac as an
      adjunct for pain control in surgical patients. As such, we sought to evaluate our
      institutional outcomes with respect to ketorolac and postoperative bleeding.
      METHODS: We retrospectively reviewed all pediatric patients undergoing
      circumcision from January 1, 2014 to December 31, 2015 at the Alberta Children's
      Hospital. Demographics, perioperative analgesic regimens, and return to emergency
      department or clinic for bleeding were gathered through chart review. RESULTS: A
      total of 475 patients undergoing circumcisions were studied, including 150 (32%)
      who received perioperative ketorolac and 325 (68%) who received standard
      analgesia. Patients receiving ketorolac were more likely to return to the
      emergency department or clinic for bleeding (ketorolac group 19/150 [13%], non
      ketorolac group 16/325 [5.0%]; p=0.005). Patients receiving ketorolac were more
      likely to have postoperative sanguineous drainage (ketorolac group 96/150 [64%],
      non-ketorolac group 150/325 [46%]; p<0.001). There was no significant difference
      in the number of patients requiring postoperative admission or further medical
      intervention. CONCLUSIONS: Although a promising analgesic, ketorolac requires
      additional investigation for safe usage in circumcisions due to possible
      increased risk of bleeding.

PMID- 29173274
TI  - Single lower calyceal percutaneous tract combined with flexible nephroscopy: A
      valuable treatment paradigm for staghorn stones.
AB  - INTRODUCTION: We evaluated the efficacy and safety of single lower calyceal tract
      combined with flexible nephroscopy for the management of staghorn renal stones by
      percutaneous nephrolithotomy. METHODS: The medical records of patients who
      underwent percutaneous nephrolithotomy for the management of staghorn stones were
      analyzed. We included patients aged >18 years, while patients with incomplete
      data and renal anatomical anomalies were excluded from the study. Stone-free
      rate, postoperative complications, procedure duration, fluoroscopy time, and
      length of hospitalization were recorded. Postoperative outcomes were evaluated by
      non-contrast computed tomography scan 4-6 weeks after the operation. Stone-free
      status was defined as the absence of residual stones >4 mm. RESULTS: The study
      cohort consisted of 103 consecutive patients. Stone-free rate was 65.0%. No
      complications were observed in 69.9% of the cases; most postoperative
      complications were Grade 1 (13.6%) and 2 (10.7%). Five patients (4.9%) suffered a
      Grade 3a complication and another patient (1.0%) suffered a Grade 3b
      complication. CONCLUSIONS: Percutaneous nephrolithotomy through a single lower
      calyceal tract combined with flexible nephroscopy can be a valuable treatment
      option for the treatment of staghorn calculi, providing efficacy and safety.
      Nevertheless, the present study is limited by both its retrospective nature and
      being conducted at a single centre and, thus, proper prospective studies with
      head-on comparisons are needed to prove or disprove the advantages and
      disadvantages of either approach.

PMID- 29173275
TI  - Images in urology: Localized primary amyloidosis of the urinary bladder.

PMID- 29173276
TI  - Do antibiotics decrease prostate-specific antigen levels and reduce the need for
      prostate biopsy in type IV prostatitis? A systematic literature review.
AB  - INTRODUCTION: Inflammation of the prostate can be a cause of elevated prostate
      specific antigen (PSA) in men referred for suspected prostate cancer. This
      systematic review assesses the evidence for antibiotic therapy in patients with
      type IV (asymptomatic) prostatitis with regard to reduction of PSA levels and
      discrimination between prostate cancer and inflammation. METHODS: MEDLINE,
      EMBASE, and the Cochrane registry were searched for papers reporting on cohorts
      of men with elevated PSA and type IV prostatitis that were treated with
      antibiotics. RESULTS: The search yielded 160 papers, of which 11 met the
      inclusion criteria: two randomized trials and nine cohort studies. In total, the
      studies reported on 1011 patients with type IV prostatitis, of whom 926 were
      treated with antibiotics. PSA normalization was seen after antibiotic treatment
      in 33.2% of patients (95% confidence interval [CI] 24.9-42.8). Meta-analysis of
      the randomized trials did not demonstrate a higher likelihood of PSA
      normalization in the antibiotics arm as compared to the control arm (odds ratio
      [OR] 1.27; 95% CI 0.58-2.76; p=0.553). Four studies performed prostate biopsies
      in all patients. Although three of these studies demonstrated lower prevalence of
      prostate cancer in patients in whom PSA had normalized, meta-analysis failed to
      show a statistically significant difference (OR 0.39; 95% CI 0.06-2.49; p=0.319).
      CONCLUSIONS: The available evidence does not support antibiotic therapy for
      differentiation between benign and malignant cause of elevated PSA in men with
      type IV prostatitis.

PMID- 29173277
TI  - Exogenous tumor necrosis factor-alpha could induce egress of Toxoplasma gondii
      from human foreskin fibroblast cells.
AB  - Toxoplasma gondii is an intra-cellular protozoan parasite that can infect almost
      all nucleated cells, eliciting host immune responses against infection. Host
      tissue damage is mainly caused by cellular lysis when T. gondii egresses from
      infected cells. However, the effects of cytokines released by host immune cells
      on egression of T. gondii remain elusive. This study aimed to investigate the
      role of tumor necrosis factor-alpha (TNF-alpha) on the egress of T. gondii from
      infected human foreskin fibroblast (HFF) cells and to elucidate the underlying
      mechanisms that regulate TNF-alpha-induced egress. Using flow cytometry to count
      tachyzoites of T. gondii released into cell culture medium, we found that egress
      of T. gondii from infected HFF cells could be induced by 10 ng/mL TNF-alpha in a
      time-dependent manner. Pre-treatment of infected HFF cells with BAPTA-AM to
      chelate intra-parasitic calcium could greatly inhibit TNF-alpha-induced egress.
      Similar results were obtained when using cytochalasin D to block parasite
      motility before the TNF-alpha-induced egress assay. In addition, blocking host
      apoptosis by Z-VAD-FMK could decrease TNF-alpha induced egress, while blocking
      necroptosis by necrostatin-1 has little impact on TNF-alpha-induced egress. The
      egressed tachyzoites displayed a normal growth rate and lost no virulence. Our
      results suggest that host cytokines could influence the cellular lytic processes
      of T. gondii, providing new insights into the relationship between host TNF-alpha
      and T. gondii pathogenesis.

PMID- 29173278
TI  - Comparison of the in vitro anthelmintic effects of Acacia nilotica and Acacia
      raddiana.
AB  - Gastrointestinal nematodes are a major threat to small ruminant rearing in the
      Sahel area, where farmers traditionally use bioactive plants to control these
      worms, including Acacia nilotica and Acacia raddiana. The main aim of this study
      was to screen the potential anthelmintic properties of aqueous and acetone
      extracts of leaves of these two plants based on three in vitro assays: (1) the
      egg hatch inhibition assay (EHA); (2) the larvae exsheathment inhibition assay
      (LEIA) using Haemonchus contortus as a model; and (3) an adult mortality test
      (AMT) applied on Caenorhabditis elegans. For the EHA, only A. raddiana was
      effective with IC50 = 1.58 mg/mL for aqueous extract, and IC50 = 0.58 mg/mL for
      acetonic extract. For the LEIA, all extracts inhibited the exsheathment of larvae
      compared to the controls, and the aqueous extract of A. nilotica was more
      larvicidal with IC50 = 0.195 mg/mL. In general, all responses to the substances
      were dose-dependent and were significantly different from the control group (p <
      0.05). For the AMT, the extracts of the two Acacia species were effective but A.
      raddiana showed greater efficacy with 100% mortality at 2.5 mg/mL and LC50 = 0.84
      mg/mL (acetonic extract). The addition of polyvinyl polypyrrolidone (PVPP) to the
      extracts suggested that tannins were responsible for blocking egg eclosion and
      inducing adult mortality but were not responsible for exsheathment inhibition.
      These results suggest that the leaves of these Acacia species possess ovicidal
      and larvicidal activities in vitro against H. contortus, and adulticidal effects
      against C. elegans.

PMID- 29173279
TI  - Are we immune by chance?
AB  - The sooner the immune system launches, the greater the chances the host has of
      survival.

PMID- 29173280
TI  - Predicting non-linear dynamics by stable local learning in a recurrent spiking
      neural network.
AB  - The brain needs to predict how the body reacts to motor commands, but how a
      network of spiking neurons can learn non-linear body dynamics using local, online
      and stable learning rules is unclear. Here, we present a supervised learning
      scheme for the feedforward and recurrent connections in a network of
      heterogeneous spiking neurons. The error in the output is fed back through fixed
      random connections with a negative gain, causing the network to follow the
      desired dynamics. The rule for Feedback-based Online Local Learning Of Weights
      (FOLLOW) is local in the sense that weight changes depend on the presynaptic
      activity and the error signal projected onto the postsynaptic neuron. We provide
      examples of learning linear, non-linear and chaotic dynamics, as well as the
      dynamics of a two-link arm. Under reasonable approximations, we show, using the
      Lyapunov method, that FOLLOW learning is uniformly stable, with the error going
      to zero asymptotically.

PMID- 29173282
TI  - Using Bioinformatics to Treat Hospitalized Smokers: Successes and Challenges of a
      Tobacco Treatment Service.
AB  - BACKGROUND: Hospitals face increasing regulations to provide and document
      inpatient tobacco treatment, yet few blueprint data exist to implement a tobacco
      treatment service (TTS). METHODS: A hospitalwide, opt-out TTS with three full
      time certified counselors was developed in a large tertiary care hospital to
      proactively treat smokers according to Chronic Care Model principles and national
      treatment guidelines. A bioinformatics platform facilitated integration into the
      electronic health record to meet evolving Centers for Medicare & Medicaid
      Services meaningful use and Joint Commission standards. TTS counselors visited
      smokers at the bedside and offered counseling, recommended smoking cessation
      medication to be ordered by the primary clinical service, and arranged for
      postdischarge resources. RESULTS: During a 3.5-year span, 21,229 smokers (31,778
      admissions) were identified; TTS specialists reached 37.4% (7,943), and 33.3%
      (5,888) of daily smokers received a smoking cessation medication order. Adjusted
      odds ratios (AORs) of receiving a chart order for smoking cessation medication
      during the hospital stay and at discharge were higher among patients the TTS
      counseled > 3 minutes and recommended medication: inpatient AOR = 7.15 (95%
      confidence interval [CI] = 6.59-7.75); discharge AOR = 5.3 (95% CI = 4.71-5.97).
      As implementation progressed, TTS counseling reach and medication orders
      increased. To assess smoking status <= 1 month postdischarge, three methods were
      piloted, all of which were limited by low follow-up rates (4.5%-28.6%).
      CONCLUSION: The TTS counseled approximately 3,000 patients annually, with
      increases over time for reach and implementation. Remaining challenges include
      the development of strategies to engage inpatient care teams to follow TTS
      recommendations, and patients postdischarge in order to optimize postdischarge
      smoking cessation.

PMID- 29173283
TI  - Using Lean Quality Improvement Tools to Increase Delivery of Evidence-Based
      Tobacco Use Treatment in Hospitalized Neurosurgical Patients.
AB  - BACKGROUND: Health care providers routinely undertreat tobacco dependence,
      indicating a need for innovative ways to increase delivery of evidence-based
      care. Lean, a set of quality improvement (QI) tools used increasingly in health
      care, can help streamline processes, create buy-in for use of evidence-based
      practices, and lead to the identification of solutions on the basis of a
      problem's root causes. To date, no published research has examined the use of
      Lean tools in tobacco dependence. A 12-month QI project using Lean tools was
      conducted to increase delivery of evidence-based tobacco use treatment (TUT) to
      hospitalized neurosurgical patients. METHODS: The study team developed a nicotine
      replacement therapy (NRT) and counseling protocol for neurosurgery inpatients who
      indicated current tobacco use and used Lean tools to increase protocol adherence.
      Rates of NRT prescription, referrals to counseling, and follow-up phone calls
      were compared pre- and postintervention. Secondary measures included patient
      satisfaction with intervention, quit rates, and reduction rates at 4 weeks
      postdischarge. RESULTS: Referrals to counseling doubled from 31.7% at baseline to
      62.0% after implementation of the intervention, and rates of nicotine replacement
      therapy (NRT) prescriptions during hospitalization and at discharge increased
      from 15.3% to 28.5% and 9.0% to 19.3%, respectively. Follow-up phone call rates
      also dramatically increased. The majority of satisfaction survey respondents
      indicated that counseling had a positive or neutral impact on stress level and
      overall satisfaction. CONCLUSION: Lean tools can dramatically increase use of
      evidence-based TUT in hospitalized patients. This project is easily replicable by
      professionals seeking to improve delivery of tobacco treatment. These findings
      may be particularly helpful to inpatient surgical departments that have
      traditionally been reticent to prescribe NRT.

PMID- 29173281
TI  - AKT isoforms have distinct hippocampal expression and roles in synaptic
      plasticity.
AB  - AKT is a kinase regulating numerous cellular processes in the brain, and
      mutations in AKT are known to affect brain function. AKT is indirectly implicated
      in synaptic plasticity, but its direct role has not been studied. Moreover, three
      highly related AKT isoforms are expressed in the brain, but their individual
      roles are poorly understood. We find in Mus musculus, each AKT isoform has a
      unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in
      neurons but displaying local differences, while AKT2 is in astrocytes. We also
      find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic
      plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through
      regulating activity-induced protein synthesis. Interestingly, AKT activity
      inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our
      studies identify distinct expression patterns and roles in synaptic plasticity
      for AKT isoforms in the hippocampus.

PMID- 29173284
TI  - Development of Patient-Centered Disability Status Questions to Address Equity in
      Care.
AB  - BACKGROUND: Patients with disabilities experience disparities in accessing and
      receiving high-quality health care services as compared to patients without
      disabilities. To address the disparities, health care organizations need to
      identify which of their patients have disabilities to track quality of care and
      provide appropriate health care accommodations. To date, no evidence-based sets
      of disability questions exist that serve these purposes. A study was conducted to
      identify patient-centered disability questions for health care organizations to
      determine which patients require health care accommodations and to track the
      quality of care experienced by patients with disabilities. METHODS: In the first
      of three phases, a focus group with patients and caregivers (N = 54) and
      interviews with providers (N = 15) were conducted to explore the disability
      questions that they believed were important. In the second phase, nationally
      recognized experts (N = 17) participated in a modified Delphi panel to develop a
      set of disability questions. The third phase entailed cognitive interviews (N =
      46) with patients with and without disabilities to refine the wording of the
      disability questions identified through the previous rounds. RESULTS: Through the
      three phases, six essential questions and three additional recommended questions
      were identified. Questions addressed hearing, visual, motor, cognitive,
      communication, and learning disabilities, and the ability to conduct activities
      of daily living. An overall question for disabilities not included in the
      previous questions was also identified. CONCLUSION: Through a rigorous, three
      stage process that engaged multiple stakeholders, patient-centered disability
      questions were identified for health care organizations to use to identify
      disparities within their organizations and accommodations that address these
      disparities.

PMID- 29173285
TI  - Expanding the Scope of the Rapid Response System.

PMID- 29173286
TI  - An Airway Rapid Response System: Implementation and Utilization in a Large
      Academic Trauma Center.
AB  - BACKGROUND: Rapid response teams mobilize resources to patients experiencing
      acute deterioration. Failed airway management results in death or anoxic brain
      injury. A codified, systems-based approach to bring personnel and equipment to
      the bedside for multidisciplinary airway assessment and rescue was reflected in
      the initial implementation of an airway rapid response (ARR) team. METHODS: A
      retrospective review of records of 117 ARR events in a 40-month period (August
      2011-November 2014) was undertaken at the Hospital of the University of
      Pennsylvania, a 789-bed, academic, urban, tertiary care, Level 1 trauma center.
      RESULTS: Of the 117 ARR events, 60 (51.3%) were called in the ICU, and 43 (36.8%)
      in the general ward. A definitive airway was secured in all patients for whom
      airway management was attempted. A new surgical airway was performed in five of
      the patients. Seven patients went to the operating room for airway management.
      Nine patients died or had care withdrawn shortly after the ARR. CONCLUSION:
      Difficult airway emergencies represent a small but critical element of airway
      rescue scenarios. Before the implementation of the ARR system, the process to
      bring the right team, equipment, expertise, and consensus on the right actions to
      critical airway emergencies was ad hoc. ARR activation, which brings
      multidisciplinary airway consultation, expert skills, and advanced airway
      equipment to the bedside, contributed to definitive airway management for
      surgical and nonsurgical airways. Performance of a bedside emergency surgical
      airway was uncommon. The ARR system represents a significant enhancement of the
      "anesthesia stat" system that typifies the airway emergency system at many
      institutions.

PMID- 29173287
TI  - Pragmatic Insights on Patient Safety Priorities and Intervention Strategies in
      Ambulatory Settings.

PMID- 29173288
TI  - Improving the Quality of Data for Inpatient Claims-Based Measures Used in Public
      Reporting and Pay-for-Performance Programs.

PMID- 29173289
TI  - User-Centered Collaborative Design and Development of an Inpatient Safety
      Dashboard.
AB  - Patient safety remains a key concern in hospital care. This article summarizes
      the iterative participatory development, features, functions, and preliminary
      evaluation of a patient safety dashboard for interdisciplinary rounding teams on
      inpatient medical services. This electronic health record (EHR)-embedded
      dashboard collects real-time data covering 13 safety domains through web services
      and applies logic to generate stratified alerts with an interactive check-box
      function. The technological infrastructure is adaptable to other EHR
      environments. Surveyed users perceived the tool as highly usable and useful.
      Integration of the dashboard into clinical care is intended to promote
      communication about patient safety and facilitate identification and management
      of safety concerns.

PMID- 29173290
TI  - Advances in Rapid Response, Patient Monitoring, and Recognition of and Response
      to Clinical Deterioration.

PMID- 29173291
TI  - Combination immune-based therapy for chronic ITP.

PMID- 29173292
TI  - Put down that smartphone and read to me!

PMID- 29173294
TI  - 50 Years Ago in The Journal of Pediatrics: Some Factors Related to Size and
      Intelligence in an Institutionalized Mentally Retarded Population.

PMID- 29173293
TI  - Genetic Testing in Children with Recurrent and Chronic Pancreatitis.

PMID- 29173295
TI  - 50 Years Ago in The Journal of Pediatrics: Subacute Sclerosing Panencephalitis.

PMID- 29173296
TI  - Waist Circumference and Body Mass Index in Children with Chronic Kidney Disease
      and Metabolic, Cardiovascular, and Renal Outcomes.
AB  - OBJECTIVE: To describe the prevalence of obesity as estimated by waist
      circumference (WC) and body mass index (BMI) and compare associations of WC and
      BMI with indicators of metabolic, cardiovascular, and renal health in children
      with chronic kidney disease (CKD). STUDY DESIGN: Cross-sectional analysis
      stratified by CKD etiology (nonglomerular or glomerular) of 737 subjects. The
      kappa statistic was used to assess agreement between the 2 measures of obesity.
      Linear regression models were performed using WC and BMI as separate independent
      variables. Dependent variables included lipid measures, insulin resistance, blood
      pressure, left ventricular mass index, proteinuria, and estimated glomerular
      filtration rate. Associations were scaled to SD and interpreted as the change in
      dependent variable associated with a 1-SD change in WC or BMI. RESULTS: There was
      good agreement (kappa statistic = 0.68) between WC and BMI in identifying
      obesity. Approximately 10% of subjects had obesity by 1 measure but not the
      other. BMI was more strongly associated with estimated glomerular filtration rate
      than WC. BMI was more strongly associated with left ventricular mass index in the
      nonglomerular CKD group compared with WC, but both had significant associations.
      The associations between WC and BMI with the remainder of the dependent variables
      were not significantly different. CONCLUSIONS: Measurement of WC added limited
      information to BMI in this cohort. Further longitudinal study is needed to
      determine how WC and BMI compare in predicting outcomes, particularly for
      children with CKD identified as having obesity by 1 measure but not the other.

PMID- 29173297
TI  - The Clinical Utility and Safety of a New Strategy for the Treatment of Refractory
      Kawasaki Disease.
AB  - OBJECTIVE: To assess the clinical utility and safety of a strategy for refractory
      Kawasaki disease, defined by Egami score >=3. STUDY DESIGN: First-line treatment
      was with intravenous methylprednisolone (30 mg/kg, 2 hours, 1 dose) plus
      intravenous immunoglobulin (2 g/kg, 24 hours) treatment. Patients resistant to
      first-line treatment received additional intravenous immunoglobulin as a second
      line treatment. Patients resistant to second-line treatment who had received
      Bacillus Calmette-Guerin vaccination 6 months earlier were treated with
      infliximab; otherwise, plasma exchange was performed. A total of 71 refractory
      patients with Kawasaki disease (median age: 2.4 years) of 365 patients with
      Kawasaki disease were treated according to our strategy from April 2007 to April
      2016. Treatment resistance was defined as a persistent fever at 36 hours after
      treatment. We evaluated coronary artery lesions at the time of the diagnosis, at
      1 month, and at 1 year after the diagnosis in accordance with the American Heart
      Association guidelines and the criteria of the Japanese Ministry of Health,
      Labour, and Welfare. RESULTS: First-line therapy was effective for 58 of 71
      patients (81.6%), and second-line therapy was effective for 9 of 13 patients
      (69.2%). At third line, 3 patients were treated by infliximab, and 1 was treated
      with plasma exchange. Of the 18 patients with coronary artery abnormalities at
      diagnosis, 13 patients at 1 month and 6 patients at 1 year had coronary artery
      dilatation (median z score 3.0, 2.6, and 1.4, respectively). There were no
      patients with coronary artery aneurysm (CAA). CONCLUSIONS: Our strategy for
      refractory Kawasaki disease was safe and effective in preventing CAA.

PMID- 29173298
TI  - Management of Congenital Heart Disease Associated with Ellis-van Creveld Short
      rib Thoracic Dysplasia.
AB  - OBJECTIVE: To evaluate clinical outcome of patients with Ellis-van Creveld
      syndrome (EVC) in whom congenital heart disease (CHD) repair was delayed
      intentionally to reduce the risk of postoperative respiratory morbidity and
      mortality. STUDY DESIGN: This retrospective review of 51 EVC c.1886+5G>T
      homozygotes born between 2005 and 2014 focused on 18 subjects who underwent
      surgery for CHD, subdivided into early (mean, 1.3 months) vs delayed (mean, 50.1
      months) repair. RESULTS: Growth trajectories differed between control subjects
      and patients with EVC, and CHD was associated with slower weight gain. Relative
      to controls, infants with EVC had a 40%-75% higher respiratory rates (independent
      of CHD) accompanied by signs of compensated respiratory acidosis. Blood gases and
      respiratory rates approached normal values by age 4 years. Hemodynamically
      significant CHD was present in 23 children, 18 (78%) of whom underwent surgical
      repair. Surgery was performed at 1.3 +/- 1.3 months for children born between
      2005 and 2009 (n = 9) and 50.1 +/- 40.2 months (P = .009) for children born
      between 2010 and 2014 (n = 9). The latter had shorter postoperative mechanical
      ventilation (1.1 +/- 2.4 days vs 49.6 +/- 57.1 days; P = .075), shorter intensive
      care duration of stay (16 +/- 24 days vs 48.6 +/- 44.2 days; P = .155), and no
      postoperative tracheostomies (vs 60%; P = .028) or deaths (vs 44%; P = .082).
      CONCLUSION: Among children with EVC and possibly other short-rib thoracic
      dysplasias, delayed surgical repair of CHD reduces postoperative morbidity and
      improves survival. Respiratory rate serves as a simple indicator for optimal
      timing of surgical repair.

PMID- 29173299
TI  - Chronic Pulmonary Insufficiency of Prematurity: Developing Optimal Endpoints for
      Drug Development.

PMID- 29173300
TI  - Persistent High Non-High-Density Lipoprotein Cholesterol in Early Childhood: A
      Latent Class Growth Model Analysis.
AB  - OBJECTIVES: To examine patterns of non-high-density lipoprotein (HDL) cholesterol
      in early childhood and identify factors associated with persistent high non-HDL
      cholesterol in healthy urban children. STUDY DESIGN: We identified all children
      enrolled in a primary care practice-based research network called TARGet Kids!
      (The Applied Research Group for Kids) with >=3 laboratory measurements of non-HDL
      cholesterol. Latent class growth model analysis was performed to identify
      distinct trajectory groups for non-HDL cholesterol. Trajectory groups were then
      categorized into "normal" vs "persistent-high" non-HDL cholesterol based on
      guideline cut-off values and logistic regression was completed to examine the
      association between trajectory group and the presence of anthropometric and
      cardiometabolic risk factors. RESULTS: A total of 608 children met inclusion
      criteria for the trajectory analysis (median age at enrolment = 18.3, IQR = 27.9
      months). Four trajectory groups were identified with 2 groups (n = 451)
      categorized as normal non-HDL cholesterol and 2 groups (n = 157) as persistent
      high non-HDL cholesterol. Family history of high cholesterol (OR 2.04, 95% CI
      1.27-3.28) was associated significantly with persistent high non-HDL cholesterol,
      whereas East/Southeast Asian vs European ethnicity (OR 0.33, 95% CI 0.14-0.78),
      longer breastfeeding duration (OR 0.96, 95% CI 0.93-1.00), and greater birth
      weight (OR 0.69, 95% CI 0.48-1.00) were associated with lower odds of persistent
      high non-HDL cholesterol. CONCLUSIONS: Patterns of non-HDL cholesterol are
      identified during early childhood, and family history of high cholesterol was
      associated most strongly with persistent high non-HDL cholesterol. Future
      research should inform the development of a clinical prediction tool for lipids
      in early childhood to identify children who may benefit from interventions to
      promote cardiovascular health.

PMID- 29173302
TI  - 50 Years Ago in The Journal of Pediatrics: Prevention and Management of Acute
      Hyperuricemia in Childhood Leukemia.

PMID- 29173301
TI  - Targeted Gene Next-Generation Sequencing in Chinese Children with Chronic
      Pancreatitis and Acute Recurrent Pancreatitis.
AB  - OBJECTIVE: To identify causal mutations in certain genes in children with acute
      recurrent pancreatitis (ARP) or chronic pancreatitis (CP). STUDY DESIGN: After
      patients were enrolled (CP, 55; ARP, 14) and their clinical characteristics were
      investigated, we performed next-generation sequencing to detect nucleotide
      variations among the following 10 genes: cationic trypsinogen protease serine 1
      (PRSS1), serine protease inhibitor, Kazal type 1 (SPINK1), cystic fibrosis
      transmembrane conductance regulator gene (CFTR), chymotrypsin C (CTRC), calcium
      sensing receptor (CASR), cathepsin B (CTSB), keratin 8 (KRT8), CLAUDIN 2 (CLDN2),
      carboxypeptidase A1 (CPA1), and ATPase type 8B member 1 (ATP8B1). Mutations were
      searched against online databases to obtain information on the cause of the
      diseases. Certain novel mutations were analyzed using the SIFT2 and Polyphen-2 to
      predict the effect on protein function. RESULTS: There were 45 patients with CP
      and 10 patients with ARP who harbored 1 or more mutations in these genes; 45
      patients had at least 1 mutation related to pancreatitis. Mutations were observed
      in the PRSS1, SPINK1, and CFTR genes in 17 patients, the CASR gene in 5 patients,
      and the CTSB, CTRC, and KRT8 genes in 1 patient. Mutations were not found in the
      CLDN, CPA1, or ATP8B1 genes. We found that mutations in SPINK1 may increase the
      risk of pancreatic duct stones (OR, 11.07; P = .003). The patients with CFTR
      mutations had a higher level of serum amylase (316.0 U/L vs 92.5 U/L; P = .026).
      CONCLUSION: Mutations, especially those in PRSS1, SPINK1, and CFTR, accounted for
      the major etiologies in Chinese children with CP or ARP. Children presenting
      mutations in the SPINK1 gene may have a higher risk of developing pancreatic duct
      stones.

PMID- 29173303
TI  - Are We Using Abdominal Radiographs Appropriately in the Management of Pediatric
      Constipation?
AB  - OBJECTIVE: To identify the reasons why pediatric gastroenterologists obtain
      abdominal radiographs in the management of pediatric constipation. STUDY DESIGN:
      This was a prospective study surveying providers regarding their rationale,
      interpretation, resultant change, and confidence in their management before and
      after obtaining KUBs in patients seen for suspected constipation. Demographics
      and clinical findings were obtained from medical records. RESULTS: A total of 24
      providers were surveyed after 72 patient encounters. Reasons for obtaining an
      abdominal radiograph included evaluation of stool burden (70%), need for a clean
      out (35%), fecal impaction (27%), cause of abdominal pain (24%), demonstration of
      stool burden to families (14%), assessment of response to therapy (13%), or
      encopresis (10%). The plan was changed in 47.6% of cases based on radiographic
      findings. In cases in which a plan was outlined before obtaining the radiograph
      (69%), the initial plan was implemented on average in 52.5%. In cases with no
      plans before obtaining the radiograph, previously unconsidered plans were
      implemented in 8.7%. Provider confidence in the management plan increased from
      2.4 +/- 2.7 to 4.1 +/- 1.8 (P < .05) after the abdominal radiograph. CONCLUSION:
      Abdominal radiographs commonly are obtained by pediatric gastroenterologists in
      the evaluation and management of constipation. The majority used it to make a
      diagnosis, and nearly one-half changed their management based on the imaging
      findings. Overall, they reported an improved confidence in their management plan,
      despite evidence that radiographic findings poorly correlate with clinical
      severity. This study highlights the need for further provider education regarding
      the recommendations delineated in existing constipation guidelines.

PMID- 29173304
TI  - Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute
      Asthma Exacerbations.
AB  - OBJECTIVE: To determine whether 2 doses of dexamethasone is as effective as 5
      days of prednisolone/prednisone therapy in improving symptoms and quality of life
      of children with asthma exacerbations admitted to the emergency department (ED).
      STUDY DESIGN: We conducted a randomized, noninferiority trial including patients
      aged 1-14 years who presented to the ED with acute asthma to compare the efficacy
      of 2 doses of dexamethasone (0.6 mg/kg/dose, experimental treatment) vs a 5-day
      course of prednisolone/prednisone (1.5 mg/kg/d, followed by 1 mg/kg/d on days 2
      5, conventional treatment). Two follow-up telephone interviews were completed at
      7 and 15 days. The primary outcome measures were the percentage of patients with
      asthma symptoms and quality of life at day 7. Secondary outcomes were unscheduled
      returns, admissions, adherence, and vomiting. RESULTS: During the study period,
      710 children who met the inclusion criteria were invited to participate and 590
      agreed. Primary outcome data were available in 557 patients. At day 7,
      experimental and conventional groups did not show differences related to
      persistence of symptoms (56.6%, 95% CI 50.6-62.6 vs 58.3%, 95% CI 52.3-64.2,
      respectively), quality of life score (80.0 vs 77.7, not significant [ns]),
      admission rate (23.9% vs 21.7%, ns), unscheduled ED return visits (4.6% vs 3.3%,
      ns), and vomiting (2.1% vs 4.4%, ns). Adherence was greater in the dexamethasone
      group (99.3% vs 96.0%, P < .05). CONCLUSION: Two doses of dexamethasone may be an
      effective alternative to a 5-day course of prednisone/prednisolone for asthma
      exacerbations, as measured by persistence of symptoms and quality of life at day
      7. CLINICAL TRIAL REGISTRATION: clinicaltrialsregister.eu: 2013-003145-42.

PMID- 29173306
TI  - Sex in journals.

PMID- 29173305
TI  - Epilepsy or a Seizure Disorder? Parental Knowledge and Misconceptions About
      Terminology.
AB  - OBJECTIVE: To assess primary caregiver understanding of the term epilepsy. STUDY
      DESIGN: A cross-sectional telephone survey evaluated understanding of the term
      epilepsy among primary caregivers of children diagnosed with epilepsy at an urban
      referral center during a 24-month period. Three measures of primary caregiver
      understanding were used: (1) identifying if their child had a seizure disorder,
      epilepsy, or both; (2) providing an open-ended definition of epilepsy; and (3)
      selecting from a multiple-choice definition of epilepsy. Caregivers with 3
      correct answers were assigned the greatest knowledge score. Associations with
      possible predictor variables were analyzed. RESULTS: Caregivers for 75 of 116
      eligible patients were contacted successfully. Of those, 55 of 75 met eligibility
      criteria; 45 of the eligible caregivers completed the survey. Twenty-six of 45
      caregivers (58%) identified that their child had both a seizure disorder and
      epilepsy, 5 of 45 (11%) provided a correct open-ended definition of epilepsy, and
      16 of 45 (36%) selected the correct multiple-choice definition. Fifteen
      caregivers (33%) had no correct answers. Seventeen (38%) answered 1, 9 (20%)
      answered 2, and 4 (9%) answered all 3 measures correctly. Caregivers with greater
      self-rated understanding had greater epilepsy knowledge scores (P = .008). Having
      a child neurologist as the first person to discuss the diagnosis with the
      caregiver also predicted a greater epilepsy knowledge score (P = .04).
      CONCLUSIONS: Most primary caregivers of children with epilepsy have a poor
      understanding of the term epilepsy. Changes are needed in how we educate
      caregivers about the meaning of this term.

PMID- 29173307
TI  - Chronic pulmonary insufficiency of prematurity: definitions matter.

PMID- 29173308
TI  - Shared Reading Quality and Brain Activation during Story Listening in Preschool
      Age Children.
AB  - OBJECTIVE: To explore the relationship between maternal shared reading quality
      (verbal interactivity and engagement) and brain function during story listening
      in at-risk, preschool-age children, in the context of behavioral evidence and
      American Academy of Pediatrics, recommendations. STUDY DESIGN: In this cross
      sectional study, 22 healthy, 4-year-old girls from low socioeconomic status
      households completed functional magnetic resonance imaging using an established
      story listening task, followed by videotaped observation of uncoached mother
      daughter reading of the same, age-appropriate picture book. Shared reading
      quality was independently scored applying dialogic reading and other evidence
      based criteria reflecting interactivity and engagement, and applied as a
      predictor of neural activation during the functional magnetic resonance imaging
      task, controlling for income and maternal education. RESULTS: Shared reading
      quality scores were generally low and negatively correlated with maternal
      distraction by smartphones (P < .05). Scores were positively correlated with
      activation in left-sided brain areas supporting expressive and complex language,
      social-emotional integration, and working memory (P <.05, false discovery rate
      corrected). CONCLUSIONS: Maternal shared reading quality is positively correlated
      with brain activation supporting complex language, executive function, and social
      emotional processing in at-risk, preschool-age children. These findings represent
      novel neural biomarkers of how this modifiable aspect of home reading environment
      may influence foundational emergent literacy skills, reinforce behavioral
      evidence and American Academy of Pediatrics, recommendations, and underscore the
      potential of dialogic reading interventions to promote healthy brain development,
      especially in at-risk households.

PMID- 29173309
TI  - Delirium in Hospitalized Children with Cancer: Incidence and Associated Risk
      Factors.
AB  - OBJECTIVE: To assess the incidence of delirium and its risk factors in
      hospitalized children with cancer. STUDY DESIGN: In this cohort study, all
      consecutive admissions to a pediatric cancer service over a 3-month period were
      prospectively screened for delirium twice daily throughout their hospitalization.
      Demographic and treatment-related data were collected from the medical record
      after discharge. RESULTS: A total of 319 consecutive admissions, including 186
      patients and 2731 hospital days, were included. Delirium was diagnosed in 35
      patients, for an incidence of 18.8%. Risk factors independently associated with
      the development of delirium included age <5 years (OR = 2.6, P = .026), brain
      tumor (OR = 4.7, P = .026); postoperative status (OR = 3.3, P = .014), and
      receipt of benzodiazepines (OR = 3.7,P < .001). Delirium was associated with
      increased hospital length of stay, with median length of stay for delirious
      patients of 10 days compared with 5 days for patients who were not delirious
      during their hospitalization (P < .001). CONCLUSIONS: In this cohort, delirium
      was a frequent complication during admissions for childhood cancer, and was
      associated with increased hospital length of stay. Multi-institutional
      prospective studies are warranted to further characterize delirium in this high
      risk population and identify modifiable risk factors to improve the care provided
      to hospitalized children with cancer.

PMID- 29173310
TI  - The Effectiveness of Trivalent Inactivated Influenza Vaccine in Children with
      Acute Leukemia.
AB  - OBJECTIVE: The objective of this study was to determine the effectiveness of
      trivalent inactivated influenza vaccine (TIV) for the prevention of laboratory
      confirmed influenza and influenza-like illnesses (ILI) among children and
      adolescents receiving therapy for acute leukemia. STUDY DESIGN: A retrospective
      review of the demographic and clinical characteristics of 498 patients at a
      pediatric cancer center who received therapy for acute leukemia during 3
      successive influenza seasons (2010-2011 through 2012-2013). RESULTS: In 498
      patient seasons with a known immunization history (median age, 6 years; range, 1
      21), 354 patients (71.1%) were immunized with TIV and 98 (19.7%) received a
      booster dose of vaccine. Vaccinated and unvaccinated patients had generally
      similar demographic characteristics. There were no differences in the overall
      rates of influenza or ILI between vaccinated and unvaccinated patients overall,
      or in any individual season. There was no difference in the rates of influenza or
      ILI between patients who received 1 dose of vaccine and those who received 2
      doses. Time to first influenza infection and time to first ILI in vaccinated and
      unvaccinated patients were not different. CONCLUSION: TIV did not protect
      children and adolescents with acute leukemia against laboratory-confirmed
      influenza or ILI. Future prospective studies should assess TIV effectiveness in
      high-risk subpopulations and alternative strategies to prevent influenza should
      be considered in this population.

PMID- 29173311
TI  - Predicting Mortality or Intestinal Failure in Infants with Surgical Necrotizing
      Enterocolitis.
AB  - OBJECTIVE: To compare existing outcome prediction models and create a novel model
      to predict death or intestinal failure (IF) in infants with surgical necrotizing
      enterocolitis (NEC). STUDY DESIGN: A retrospective, observational cohort study
      conducted in a 2-campus health system in Atlanta, Georgia, from September 2009 to
      May 2015. Participants included all infants <=37 weeks of gestation with surgical
      NEC. Logistic regression was used to model the probability of death or IF, as a
      composite outcome, using preoperative variables defined by specifications from 3
      existing prediction models: American College of Surgeons National Surgical
      Quality Improvement Program Pediatric, Score for Neonatal Acute Physiology
      Perinatal Extension, and Vermont Oxford Risk Adjustment Tool. A novel
      preoperative hybrid prediction model was also derived and validated against a
      patient cohort from a separate campus. RESULTS: Among 147 patients with surgical
      NEC, discrimination in predicting death or IF was greatest with American College
      of Surgeons National Surgical Quality Improvement Program Pediatric (area under
      the receiver operating characteristic curve [AUC], 0.84; 95% CI, 0.77-0.91) when
      compared with the Score for Neonatal Acute Physiology Perinatal Extension II
      (AUC, 0.60; 95% CI, 0.48-0.72) and Vermont Oxford Risk Adjustment Tool (AUC,
      0.74; 95% CI, 0.65-0.83). A hybrid model was developed using 4 preoperative
      variables: the 1-minute Apgar score, inotrope use, mean blood pressure, and
      sepsis. The hybrid model AUC was 0.85 (95% CI, 0.78-0.92) in the derivation
      cohort and 0.77 (95% CI, 0.66-0.86) in the validation cohort. CONCLUSIONS:
      Preoperative prediction of death or IF among infants with surgical NEC is
      possible using existing prediction tools and, to a greater extent, using a newly
      proposed 4-variable hybrid model.

PMID- 29173312
TI  - Treatment of Children with Persistent and Chronic Idiopathic Thrombocytopenic
      Purpura: 4 Infusions of Rituximab and Three 4-Day Cycles of Dexamethasone.
AB  - OBJECTIVES: To assess initial and long-term outcome of children with
      persistent/chronic idiopathic thrombocytopenic purpura (ITP) treated with 4
      infusions of rituximab and three 4-day cycles of dexamethasone (4R+3Dex)
      including cohorts with most benefit and/or treatment associated toxicity. STUDY
      DESIGN: All pediatric patients with ITP at Weill-Cornell who received 4R+3Dex
      were included in this retrospective study. Duration was median time from first
      rituximab infusion to treatment failure. Patient cohort included 33 children ages
      1-18 years with persistent/chronic ITP; 19 were female, 10 of whom were
      adolescents. Every patient had failed more than 1 and usually several ITP
      treatments. RESULTS: Children were treated with rituximab, 375 mg/m2 weekly for 4
      weeks and three 4-day courses of dexamethasone 28 mg/m2 (40 mg max). Average age
      of nonresponders was 7.75 years, and initial responders averaged 12.7 years (P =
      .0073); 30% maintained continuing response at 60 months or last check-up. Eight
      of the 10 patients who underwent remission were female with ITP <24 months prior
      to initiating 4R+3Dex. All responding male patients except 2 relapsed.
      CONCLUSIONS: Durable unmaintained ITP remission after 4R+3Dex was seen almost
      exclusively in female adolescents with <24 months duration of ITP. This provides
      a new therapeutic paradigm for a subpopulation with hard-to-treat chronic ITP.
      The pathophysiology of ITP underlying this distinction requires further
      elucidation.

PMID- 29173313
TI  - Urgent Care Utilization in the Pediatric Medicaid Population.
AB  - OBJECTIVE: To assess healthcare utilization patterns associated with high (>=3
      visits/year) urgent care utilization. STUDY DESIGN: Retrospective analysis of 2
      723 792 children who were less than 19 years of age in the 2013 Marketscan
      Medicaid database. Healthcare utilization categorized as inpatient, emergency
      department, urgent care, well-child primary care provider (PCP), acute PCP, and
      specialist visits was documented for 4 groups. We hypothesized that children with
      high urgent care utilization would have decreased utilization at other sites of
      care. Multivariable logistic models compared the odds of high urgent care
      utilization. RESULTS: Of children in the study population, 92.0% had no urgent
      care visits; 4.7% had 1; 1.5% had 2; and 1.0% had >=3. Patient attributes of high
      urgent care utilization were: ages 1-2 years (aOR = 2.32, 95% CI: 2.18-2.36,
      reference group: 13-18 years), presence of a complex chronic condition (CCC) (aOR
      = 1.98, 95% CI: 1.88-2.07, reference group: no CCC) and no CCC but >=3 chronic
      conditions (aOR = 2.85, 95% CI: 2.73-2.97, reference group: no CCC, no chronic
      conditions). High urgent care utilization was associated with >=5 PCP visits for
      acute care (aOR = 1.16, 95% CI: 1.11-1.20, reference group: 0 visits), and >=3
      emergency department visits (aOR = 2.15, 95% CI: 2.10-2.23, reference group: 0
      visits). CONCLUSIONS: Increased urgent care utilization was associated with an
      increase in overall healthcare utilization. Even though those with higher urgent
      care utilization had more visits for acute care, patients continued to see their
      PCP for both well-child and acute care visits.

PMID- 29173314
TI  - Risky Business: Meeting the Structural Needs of Transdisciplinary Science.

PMID- 29173315
TI  - Chlorhexidine-Induced Chemical Burns in Very Low Birth Weight Infants.
AB  - Skin disinfection with chlorhexidine gluconate has not been standardized in
      preterm infants. We present 5 cases of chemical burns that occurred within the
      first 2 days of life in very low birth weight neonates after skin disinfection
      with aqueous and alcohol-based chlorhexidine solutions.

PMID- 29173316
TI  - A Novel Mutation in Junctional Plakoglobin Causing Lethal Congenital
      Epidermolysis Bullosa.
AB  - We report a case of neonatal generalized erythema and epidermolysis resulting
      from a novel mutation in the junctional plakoglobin gene causing truncation of
      the plakoglobin protein. Expedited genetic testing enabled diagnosis while the
      patient was in the neonatal intensive care unit, providing valuable information
      for the clinicians and family.

PMID- 29173317
TI  - Dosing wisely: caffeine and the preterm infant.

PMID- 29173318
TI  - Congenital diaphragmatic hernia: is the heart the problem?

PMID- 29173320
TI  - Pulmonary Artery Pressures in School-Age Children Born Prematurely.
AB  - OBJECTIVES: To test the hypothesis that pulmonary artery pressures were higher in
      school aged children born extremely premature than those born at term. We also
      wanted to assess whether pulmonary artery pressures differed between children
      born prematurely with or without bronchopulmonary dysplasia (BPD) or between
      those randomized in the neonatal period to different ventilation modes. STUDY
      DESIGN: Transthoracic echocardiography was performed on 193 children born
      extremely premature (106 had BPD) and 110 children born at term when they were 11
      14 years of age. Ninety-nine children born extremely premature had been supported
      by high-frequency oscillation and 94 by conventional ventilation. Tricuspid
      regurgitation was assessed in the apical 4-chamber and modified parasternal long
      axis views. Continuous-wave Doppler of the peak regurgitant jet velocity was used
      to estimate the right-ventricular-to-right-atrial systolic pressure gradient.
      RESULTS: Tricuspid regurgitation was measurable in 71% (137/193) of the children
      born preterm and 75% (83/110) of the children born at term (P .23). The children
      born prematurely compared with the children born at term had a greater peak
      tricuspid regurgitation velocity (2.21 vs 1.95 m/s, P < .001) and the children
      born prematurely who had BPD vs those without BPD had a greater peak tricuspid
      regurgitation velocity (P = .023). There were no significant differences in
      pulmonary artery pressures according to neonatal ventilation mode. CONCLUSIONS:
      Pulmonary artery pressures were estimated to be greater in 11- to 14-year-old
      children born extremely prematurely compared with those born at term and in those
      born prematurely who developed BPD compared with those who did not but did not
      differ significantly by neonatal ventilation mode.

PMID- 29173322
TI  - 50 Years Ago in The Journal of Pediatrics: Public Knowledge of Ipecac Syrup in
      the Management of Accidental Poisonings.

PMID- 29173321
TI  - Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in
      Preterm Neonates.
AB  - OBJECTIVE: To identify dosing strategies that will assure stable caffeine
      concentrations in preterm neonates despite changing caffeine clearance during the
      first 8 weeks of life. METHODS: A 3-step simulation approach was used to compute
      caffeine doses that would achieve stable caffeine concentrations in the first 8
      weeks after birth: (1) a mathematical weight change model was developed based on
      published weight distribution data; (2) a pharmacokinetic model was developed
      based on published models that accounts for individual body weight, postnatal,
      and gestational age on caffeine clearance and volume of distribution; and (3)
      caffeine concentrations were simulated for different dosing regimens. RESULTS: A
      standard dosing regimen of caffeine citrate (using a 20 mg/kg loading dose and 5
      mg/kg/day maintenance dose) is associated with a maximal trough caffeine
      concentration of 15 mg/L after 1 week of treatment. However, trough
      concentrations subsequently exhibit a clinically relevant decrease because of
      increasing clearance. Model-based simulations indicate that an adjusted
      maintenance dose of 6 mg/kg/day in the second week, 7 mg/kg/day in the third to
      fourth week and 8 mg/kg/day in the fifth to eighth week assures stable caffeine
      concentrations with a target trough concentration of 15 mg/L. CONCLUSIONS: To
      assure stable caffeine concentrations during the first 8 weeks of life, the
      caffeine citrate maintenance dose needs to be increased by 1 mg/kg every 1-2
      weeks. These simple adjustments are expected to maintain exposure to stable
      caffeine concentrations throughout this important developmental period and might
      enhance both the short- and long-term beneficial effects of caffeine treatment.

PMID- 29173319
TI  - Impact of the Neonatal Resuscitation Program-Recommended Low Oxygen Strategy on
      Outcomes of Infants Born Preterm.
AB  - OBJECTIVE: To evaluate the impact of the Neonatal Resuscitation Program (NRP)
      recommended low oxygen strategy (LOX) on neonatal morbidities, mortality, and
      neurodevelopmental outcomes in neonates born preterm. STUDY DESIGN: In March
      2011, Parkland Hospital changed from a high oxygen strategy (HOX) of
      resuscitation with initial 100% oxygen and targeting 85%-94% oxygen saturation
      for delivery room resuscitation to a LOX with initial 21% oxygen and titrating
      oxygen to meet NRP-recommended transitional target saturations. Neonates <=28
      weeks' gestational age born between August 2009 and April 2012 were identified.
      In this retrospective, observational study, neonates exposed to LOX vs HOX were
      compared for short-term morbidity, mortality, and long-term neurodevelopmental
      outcomes. Regression analysis was performed to control for confounding variables.
      RESULTS: Of 199 neonates, 110 were resuscitated with HOX and 89 with LOX.
      Compared with HOX, neonates exposed to LOX had lower oxygen exposure in the
      delivery room (5.2 +/- 1.5 vs 7.8 +/- 2.8 [?FiO2 * time min], P < .01), spent
      fewer days on oxygen (30 [5, 54] vs 46 [11, 82], P = .01), and had lower odds of
      developing bronchopulmonary dysplasia (aOR 0.4 [0.2, 0.9]). There was no
      difference in mortality (17 [20%] vs 20 [18%]), but neonates exposed to LOX had
      greater motor composite scores on Bayley Scales of Infant and Toddler Development
      Third edition assessment (91 [85, 97] vs 88 [76, 94], P < .01). CONCLUSION: The
      NRP-recommended LOX strategy was associated with improved respiratory morbidities
      and neurodevelopmental outcomes with no increase in mortality. Prospective trials
      to confirm the optimal oxygen strategy for the resuscitation of neonates born
      preterm are needed.

PMID- 29173324
TI  - Probiotics for Colic-Is the Gut Responsible for Infant Crying After All?

PMID- 29173323
TI  - Delayed Breastfeeding Initiation Is Associated with Infant Morbidity.
AB  - OBJECTIVE: To assess the relationship between breastfeeding initiation time and
      postneonatal mortality, morbidity, and growth through 24 months in a cohort of
      Tanzanian infants. STUDY DESIGN: We included 4203 infants from 2 trials of
      micronutrient supplementation. We used Cox proportional hazards models or general
      estimating equations to estimate relative risks. RESULTS: A total of 13% of
      infants initiated breastfeeding >1 hour after birth (n = 536). There was no
      association between breastfeeding initiation time and risk of all-cause or cause
      specific mortality, nor infant growth failure, from 6 weeks to 2 years of age.
      However, delayed breastfeeding was associated with an increased risk of several
      common infectious morbidities in early infancy, including upper respiratory
      infection symptoms and vomiting. Compared with those who initiated breastfeeding
      within the first hour of birth, delayed breastfeeding initiation was associated
      with an 11% increased risk of cough (relative risk 1.11, 95% CI 1.02-1.21) and a
      48% increased risk of difficulty breathing (relative risk 1.48, 95% CI 1.09-2.01)
      during the first 6 months. Delayed initiation was associated with a greater risk
      of difficulty breathing from 6 to 12 months of age, but it was not associated
      with risk of any other morbidity during this time, nor any morbidity between 12
      and 24 months. CONCLUSION: Delayed breastfeeding initiation is associated with an
      increased risk of infant morbidity during the first 6 months of life. Early
      breastfeeding initiation, along with exclusive and prolonged breastfeeding,
      should be prioritized and promoted in efforts to improve child health.

PMID- 29173325
TI  - Intestinal Microbiota Composition in Sudden Infant Death Syndrome and Age-Matched
      Controls.
AB  - OBJECTIVE: To assess whether features of the infant intestinal microbiome,
      including the carriage of toxigenic bacteria, are associated with sudden infant
      death syndrome (SIDS). STUDY DESIGN: We undertook a case-controlled analysis of
      fecal microbiology in SIDS. Fecal material was obtained from 44 cases and 44 aged
      matched controls. Microbiota composition was determined by 16S ribosomal RNA gene
      amplicon sequencing and comparisons between cases and controls made based on both
      bacterial alpha diversity measures and unconstrained ordination. Specific
      quantitative polymerase chain reaction assays were used to determine intestinal
      carriage of Staphylococcus aureus, toxigenic Clostridium difficile, and
      pathogenic and nonpathogenic Escherichia coli. RESULTS: The microbial composition
      for the study population as a whole was consistent with previous studies of
      infants <12 months of age, with a correlation between alpha diversity and age (r2
      = 0.08; P = .007). However, no difference was observed in alpha diversity between
      SIDS cases and controls (P > .4). Nonmetric multidimensional scaling also
      revealed no evidence of differences in microbiota dispersal between SIDS cases
      and controls (P = .4, permutational multivariate ANOVA test; Pseudo-F = 0.9), nor
      was a difference observed in microbiota dispersion (P = .19, PERMDISP test; F =
      1.9). There were no significant intergroup differences in the carriage of S
      aureus, toxigenic C difficile, total E coli, or pathogenic E coli. CONCLUSIONS:
      We found no evidence of an association between altered intestinal microbiology
      and SIDS, or to support the development of strategies to reduce the incidence of
      SIDS that target intestinal microbiology.

PMID- 29173326
TI  - Capillary Blood Ketone Levels as an Indicator of Inadequate Breast Milk Intake in
      the Early Neonatal Period.
AB  - OBJECTIVE: To determine the utility of capillary blood ketone levels as an
      indicator of inadequate intake of breast milk in the early postnatal period.
      STUDY DESIGN: Levels of capillary blood beta-hydroxybutyrate (betaOHB), the main
      ketone body in the blood, were measured with a bedside ketone meter in 585 full
      term neonates aged 48-95 hours who were breastfed exclusively. Relationships
      between weight-loss percentage, blood sodium, glucose, pH, partial pressure of
      carbon dioxide, base-deficit levels, and betaOHB levels were investigated. The
      diagnostic accuracy of betaOHB for predicting excessive weight loss (weight loss
      >=10% of birth weight) and hypernatremic dehydration (blood sodium level >=150
      mEq/L) was determined. RESULTS: betaOHB levels were correlated positively with
      weight-loss percentage and blood sodium levels and were correlated negatively
      with blood glucose levels. The diagnostic accuracy of betaOHB was 0.846 (optimal
      cut off, 1.55 mmol/L; sensitivity, 80.9%, specificity, 74.0%) for predicting
      excessive weight loss and 0.868 (optimal cut off, 1.85 mmol/L; sensitivity,
      94.3%; specificity, 69.9%) for predicting hypernatremic dehydration according to
      the area under the receiver operating characteristic curve. Multiple logistic
      analysis revealed that betaOHB and weight loss percentage were the only
      independent predictors of hypernatremic dehydration. Increases in betaOHB levels
      also were associated with worsening metabolic acidosis and hypocapnia.
      CONCLUSION: High betaOHB levels were associated with inadequate intake of breast
      milk in the early postnatal period. The use of bedside capillary blood ketone
      levels may be clinically useful as an indicator of dehydration, energy depletion,
      and acid-base imbalance in breastfeeding infants in the early postnatal period.

PMID- 29173327
TI  - Cardiac Biomarker Release after Endurance Exercise in Male and Female Adults and
      Adolescents.
AB  - OBJECTIVES: To compare the responses of high-sensitivity cardiac troponin T (hs
      cTnT) and NH2-terminal probrain natriuretic peptide (NT-proBNP) after 60 minutes
      of swimming in male and female adults and adolescents with different pubertal
      status. STUDY DESIGN: Adolescent swimmers (25 male and 25 female) and adult
      swimmers (7 male and 9 female) participated in a 60-minute maximal swimming test
      with serial assessment of hs-cTnT and NT-proBNP at rest, immediately
      postexercise, and at 1, 3, 6, 12, and 24 hours postexercise. Adolescents were
      classified according to pubertal status: Tanner stages 3 (n = 14), 4 (n = 22),
      and 5 (n = 14). RESULTS: Exercise resulted in an increase in both biomarkers. hs
      cTnT responses to exercise were similar in adolescents with different pubertal
      status and adults, although there was substantial individual variability in peak
      hs-cTnT, with the upper reference limit exceeding in 62% of the participants.
      Postexercise kinetics for hs-cTnT were largely consistent across all groups with
      a return to near baseline levels 24 hours postexercise. The male participants
      showed higher values of hs-cTnT at baseline and postexercise. All groups had
      similar NT-proBNP responses to acute exercise and recovery. One swimmer exceeded
      the upper reference limit for NT-proBNP. CONCLUSIONS: An exercise-associated
      increase in hs-cTnT and NT-proBNP occurred in response to a 60-minute maximal
      swimming test that was independent of pubertal status/adolescent vs adults. The
      present data also suggests that baseline and postexercise hs-cTnT values are
      higher in male compared with female, with no sex differences in NT-proBNP values.

PMID- 29173328
TI  - Editorial overview: Autoimmunity: New genomics approaches are improving our
      understanding of autoimmunity.

PMID- 29173329
TI  - A cause celebre: Can we agree on a common definition or model for causation?

PMID- 29173330
TI  - Correction.

PMID- 29173331
TI  - Dental disease before radiotherapy in patients with head and neck cancer:
      Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients.
AB  - BACKGROUND: No evidence-based guidelines exist for preventive dental care before
      radiation therapy (RT) in patients with head and neck cancer (HNC). An ongoing
      multicenter, prospective cohort study, Clinical Registry of Dental Outcomes in
      Head and Neck Cancer Patients (OraRad), is addressing this knowledge gap. The
      authors evaluated the level of dental disease before RT in the OraRad cohort,
      factors associated with dental disease, and dental treatment recommendations made
      before RT. METHODS: As part of OraRad, the authors assessed caries, periodontal
      disease, dental recommendations, and dental interventions performed before RT.
      RESULTS: Baseline measures were reported for 356 participants (77% men) with mean
      (standard deviation) age of 59.9 (11.0) years. Measures included mean number of
      teeth (22.9), participants with at least 1 tooth with caries (37.2%), and
      participants with at least 1 tooth with probing depth 5 millimeters or greater
      (47.4%). Factors associated with less extensive dental disease before RT included
      having at least a high school diploma, having dental insurance, history of
      routine dental care, and a smaller tumor size (T1 or T2). Based on the dental
      examination before RT, 163 (49.5%) participants had dental treatment recommended
      before RT, with extractions recommended most frequently. CONCLUSION: Many
      patients with HCN require dental treatment before RT; more than one-third require
      extractions. PRACTICAL IMPLICATIONS: Most patients have some level of dental
      disease at the start of RT, indicating the importance of dental evaluation before
      RT. By observing dental outcomes after RT, OraRad has the potential to determine
      the best dental treatment recommendations for patients with HCN.

PMID- 29173332
TI  - Oral health status and longitudinal cardiometabolic risk in a national sample of
      young adults.
AB  - BACKGROUND: Dental and cardiometabolic diseases are highly prevalent, share many
      common risk factors, and begin during youth. Despite poor dental health being
      known to influence dietary behaviors that are in turn linked to cardiometabolic
      health, the role of oral health on concomitant and future cardiometabolic disease
      is understudied. We sought to determine the association of oral health with
      cardiometabolic markers during adolescence and early adulthood. METHODS: Our
      sample included 11,556 participants with data from waves 1 (when participants
      were aged 12 to 19 years) and 4 (when they were aged 26 to 32 years) of the
      National Longitudinal Study of Adolescent to Adult Health. Multivariable linear
      and logistic regression separately examined associations between different
      markers of oral health (that is, missing teeth, periodontal disease, and deferred
      dental care) and markers of cardiometabolic health (that is, lipids, blood
      pressure, and body mass index), adjusting for sociodemographic characteristics.
      RESULTS: Mean age was 29 years at follow-up (wave 4). In adjusted analyses,
      deferred dental care during both adolescence (beta = 1.25; 95% confidence
      interval [CI], 0.6 to 2.0; P = .001) and early adulthood (beta = 0.9; 95% CI, 0.4
      to 1.3; P < .001) was associated with an increased body mass index during early
      adulthood. Deferred dental care in early adulthood was also associated with
      increased systolic (beta = 0.9; 95% CI, 0.4 to 1.5; P = .002) and diastolic (beta
      = 1.0; 95% CI, 0.5 to 1.5; P < .001) blood pressure values and an increased
      likelihood of being hypertensive (odds ratio = 1.2; 95% CI, 1.0 to 1.3; P = .03).
      CONCLUSIONS: In this nationally representative study deferred dental care during
      adolescence and concurrently in early adulthood was associated with poorer
      cardiometabolic disease during early adulthood. Providing better access to dental
      care may have benefits not only for oral health but also for long-term
      cardiometabolic health. PRACTICAL IMPLICATIONS: Deferred dental care during
      adolescence and early adulthood, but not recent tooth loss or periodontal
      disease, is associated with increased risk of cardiometabolic disease.

PMID- 29173333
TI  - Knocking tobacco out.

PMID- 29173334
TI  - Recent Court Ruling in Japan Exemplifies Another Layer of Regulation for
      Regenerative Therapy.

PMID- 29173335
TI  - Invited Commentary.

PMID- 29173336
TI  - Lung Cancer Screening: Where Do Surgeons Stand?

PMID- 29173337
TI  - Medical Rules of Disengagement.

PMID- 29173338
TI  - Organ Donation and Ethical Practices.

PMID- 29173339
TI  - Fibrinolysis Shutdown in Severely Injured Trauma Patients: A New World to
      Explore.

PMID- 29173340
TI  - Persistent Fibrinolysis Shutdown: In reply to Tonglet and colleagues.

PMID- 29173341
TI  - December 2017 Featured Articles, Volume 225.

PMID- 29173342
TI  - Correction.

PMID- 29173343
TI  - Multifaceted processes controlling the distribution of hazardous compounds in the
      spontaneous combustion of coal and the effect of these compounds on human health.
AB  - Pollution generated by hazardous elements and persistent organic compounds that
      affect coal fire is a major environmental concern because of its toxic nature,
      persistence, and potential risk to human health. The coal mining activities are
      growing in the state of Santa Catarina in Brazil, thus the collateral impacts on
      the health and economy are yet to be analyzed. In addition, the environment is
      also enduring the collateral damage as the waste materials directly influence the
      coal by-products applied in civil constructions. This study was aimed to
      establish the relationships between the composition, morphology, and structural
      characteristics of ultrafine particles emitted by coal mine fires. In Brazil, the
      self-combustions produced by Al-Ca-Fe-Mg-Si coal spheres are rich in chalcophile
      elements (As, Cd, Cu, Hg, Pb, Sb, Se, Sn, and Zn), lithophile elements (Ce, Hf,
      In, La, Th, and U), and siderophile elements (Co, Cr, Mo, Fe, Ni, and V). The
      relationship between nanomineralogy and the production of hazardous elements as
      analyzed by advanced methods for the geochemical analysis of different materials
      were also delineated. The information obtained by the mineral substance analysis
      may provide a better idea for the understanding of coal-fire development and
      assessing the response of particular coal in different combustion processes.

PMID- 29173344
TI  - Consider Making Public Policy a Part of Your New Year.

PMID- 29173345
TI  - Prepare for a New Year with Real Solutions You Can Use.

PMID- 29173347
TI  - Dietary Energy Density in the Australian Adult Population from National Nutrition
      Surveys 1995 to 2012.
AB  - BACKGROUND: It is hypothesized that the observed proliferation of energy-dense,
      nutrient-poor foods globally is an important contributing factor to the
      development of the obesity epidemic. However, evidence that the population's
      dietary energy density has increased is sparse. The World Cancer Research Fund
      recommends that dietary energy density be <1.25 kcal/g to prevent weight gain.
      OBJECTIVE: The aim of this research was to determine whether the dietary energy
      density of the Australian population has changed between 1995 and 2012. DESIGN: A
      secondary analysis of two cross-sectional Australian national nutrition surveys
      from 1995 and 2011/2012 was conducted. PARTICIPANTS/SETTING: Participants of the
      surveys included adults aged 18 years and older (1995 n=10,986 and 2011/2012
      n=9,435) completing 24-hour dietary recalls, including a second recall for a
      subset of the population (10.4% in 1995 and 64.6% in 2011/2012). MAIN OUTCOME
      MEASURES: Outcome measures included the change in dietary energy density
      (calculated as energy/weight of food [kcal/g] for food only) between surveys.
      STATISTICAL ANALYSIS: The National Cancer Institute method for "estimating ratios
      of two dietary components that are consumed nearly every day" was used to
      determine the usual distribution and the percentage of participants reporting
      energy density <1.25 kcal/g. RESULTS: The mean (standard deviation) dietary
      energy density was 1.59 (0.26) kcal/g and 1.64 (0.32) kcal/g (P<0.0001) in 1995
      and 2011/2012, respectively, with 13% and 5% (P<0.0001) of the population meeting
      dietary energy-density recommendations. For those aged 70 years and older, the
      percentage with energy density <1.25 kcal/g decreased from 22% to 6% (P<0.0001)
      for men and from 33% to 11% (P<0.0001) for women in 1995 and 2011/2012,
      respectively. Among those aged 18 to 29 years, 1% of men in both surveys (P=0.8)
      and 4% of women in 1995 and 2% in 2011/2012 (P=0.01) reported energy density
      <1.25 kcal/g. CONCLUSIONS: Dietary energy density has increased between the two
      surveys and few people consumed low energy-dense diets in line with
      recommendations. The change was largely due to increased energy density of older
      adult's diets, while young adults had high dietary energy density at both time
      points. These data suggest efforts now focus on the evaluation of the role of
      modifying energy density of the diet to reduce the risk of weight gain in adults.

PMID- 29173346
TI  - From Neighborhood to Genome: Three Decades of Nutrition-Related Research from the
      Atherosclerosis Risk in Communities Study.

PMID- 29173348
TI  - Use of Added Sugars Instead of Total Sugars May Improve the Capacity of the
      Health Star Rating System to Discriminate between Core and Discretionary Foods.
AB  - BACKGROUND: The Australian Government has introduced a voluntary front-of-package
      labeling system that includes total sugar in the calculation. OBJECTIVE: Our aim
      was to determine the effect of substituting added sugars for total sugars when
      calculating Health Star Ratings (HSR) and identify whether use of added sugars
      improves the capacity to distinguish between core and discretionary food
      products. DESIGN: This study included packaged food and beverage products
      available in Australian supermarkets (n=3,610). The product categories included
      in the analyses were breakfast cereals (n=513), fruit (n=571), milk (n=309), non
      alcoholic beverages (n=1,040), vegetables (n=787), and yogurt (n=390). Added
      sugar values were estimated for each product using a validated method. HSRs were
      then estimated for every product according to the established method using total
      sugar, and then by substituting added sugar for total sugar. The scoring system
      was not modified when added sugar was used in place of total sugar in the HSR
      calculation. Products were classified as core or discretionary based on the
      Australian Dietary Guidelines. To investigate whether use of added sugar in the
      HSR algorithm improved the distinction between core and discretionary products as
      defined by the Australian Dietary Guidelines, the proportion of core products
      that received an HSR of >=3.5 stars and the proportion of discretionary products
      that received an HSR of <3.5 stars, for algorithms based upon total vs added
      sugars were determined. RESULTS: There were 2,263 core and 1,347 discretionary
      foods; 1,684 of 3,610 (47%) products contained added sugar (median 8.4 g/100 g,
      interquartile range=5.0 to 12.2 g). When the HSR was calculated with added sugar
      instead of total sugar, an additional 166 (7.3%) core products received an HSR of
      >=3.5 stars and 103 (7.6%) discretionary products received a rating of >=3.5
      stars. The odds of correctly identifying a product as core vs discretionary were
      increased by 61% (odds ratio 1.61, 95% CI 1.26 to 2.06; P<0.001) when the
      algorithm was based on added compared to total sugars. CONCLUSIONS: In the six
      product categories examined, substitution of added sugars for total sugars better
      aligned the HSR with the Australian Dietary Guidelines. Future work is required
      to investigate the impact in other product categories.

PMID- 29173349
TI  - Position of the Academy of Nutrition and Dietetics: Food Insecurity in the United
      States.
AB  - It is the position of the Academy of Nutrition and Dietetics that systematic and
      sustained action is needed to achieve food and nutrition security in the United
      States. To achieve food security, effective interventions are needed, along with
      adequate funding for, and increased utilization of, food and nutrition assistance
      programs; inclusion of nutrition education in such programs; strategies to
      support individual and household economic stability; and research to measure
      impact on food insecurity- and health-related outcomes. Millions of individuals
      living in the United States experience food insecurity. Negative nutritional and
      non-nutritional outcomes are associated with food insecurity across the lifespan,
      including substandard academic achievement, inadequate intake of key nutrients,
      increased risk for chronic disease, and poor psychological and cognitive
      functioning. Registered dietitian nutritionists and nutrition and dietetics
      technicians, registered, play key roles in addressing food insecurity and are
      uniquely positioned to make valuable contributions through competent and
      collaborative practice, provision of comprehensive food and nutrition education
      and training, innovative research related to all aspects of food insecurity, and
      advocacy efforts at the local, state, regional, and national levels.

PMID- 29173350
TI  - The Distribution of Plasma Electrolytes.

PMID- 29173351
TI  - Is Healthcare a Human Right? No.

PMID- 29173352
TI  - Is Healthcare a Human Right? Yes.

PMID- 29173353
TI  - Extracellular Microvesicles as Game Changers in Better Understanding the
      Complexity of Cellular Interactions-From Bench to Clinical Applications.
AB  - Recent research has led to wide acceptance and better understanding of a novel
      mechanism for cell-cell communication that employs a network of extracellular
      microvesicles (ExMVs). Derived from the plasma membrane or the endosomal membrane
      compartment, these small, spherical membrane fragments are secreted from the cell
      surface or in the process of exocytosis from endosomal membrane compartment and
      (1) with ligands expressed on their surface directly stimulate target cells in a
      paracrine manner, (2) transfer cell membrane receptors to target cells or (3)
      deliver encapsulated messenger RNA, microRNA, proteins and bioactive lipids to
      target cells. This represents an evolutionarily ancient mechanism by which cells
      signal their presence in the microenvironment, communicate with each other and
      affect the biology of neighboring cells. Evidence suggests the pivotal role of
      ExMVs in almost all biological processes within the body as well as their
      involvement in certain pathologies. Moreover, liquid biopsies based on
      deciphering the molecular signature of ExMVs promise to revolutionize laboratory
      diagnostics. At the same time, there are ongoing attempts to employ them as
      delivery vehicles for drugs as well as therapeutics in regenerative medicine,
      oncology and immunotherapy.

PMID- 29173354
TI  - Plasma Electrolyte Distributions in Humans-Normal or Skewed?
AB  - BACKGROUND: It is widely believed that plasma electrolyte levels are normally
      distributed. Statistical tests and calculations using plasma electrolyte data are
      often reported based on this assumption of normality. Examples include t tests,
      analysis of variance, correlations and confidence intervals. The purpose of our
      study was to determine whether plasma sodium (Na+), potassium (K+), chloride (Cl
      ) and bicarbonate [Formula: see text] distributions are indeed normally
      distributed. METHODS: We analyzed plasma electrolyte data from 237 consecutive
      adults (137 women and 100 men) who had normal results on a standard basic
      metabolic panel which included plasma electrolyte measurements. The skewness of
      each distribution (as a measure of its asymmetry) was compared to the zero
      skewness of a normal (Gaussian) distribution. RESULTS: The plasma Na+
      distribution was skewed slightly to the right, but the skew was not significantly
      different from zero skew. The plasma Cl- distribution was skewed slightly to the
      left, but again the skew was not significantly different from zero skew. On the
      contrary, both the plasma K+ and [Formula: see text] distributions were
      significantly skewed to the right (P < 0.01 zero skew). There was also a
      suggestion from examining frequency distribution curves that K+ and [Formula: see
      text] distributions were bimodal. CONCLUSIONS: In adults with a normal basic
      metabolic panel, plasma potassium and bicarbonate levels are not normally
      distributed and may be bimodal. Thus, statistical methods to evaluate these 2
      plasma electrolytes should be nonparametric tests and not parametric ones that
      require a normal distribution.

PMID- 29173355
TI  - Bedside Blood Glucose Monitoring in Critically Ill Patients: Comparison Between
      Arterial and Capillary Glucose.
AB  - BACKGROUND: Critically ill patients are at high risk of hypoglycemia and are
      particularly vulnerable to unrecognized hypoglycemia. Close blood glucose
      monitoring is therefore crucial. There are several options to conduct frequent
      blood glucose measurement and a number of conditions in intensive care unit
      patients may affect the accuracy of blood glucose measurement. The aim of the
      study was to compare the accuracy of capillary glucose by bedside glucometer with
      arterial samples by bedside glucometer and arterial samples by blood gas analyzer
      in critically ill patients through a prospective case-control study. MATERIALS
      AND METHODS: Arterial and capillary samples from 60 patients were taken
      simultaneously and were tested immediately at the bedside. Results of the paired
      measurements were compared and expressed as a correlation coefficient. RESULTS:
      Capillary glucose in the study group and control group were 9.73 +/- 2.28mmol/L
      and 8.9 +/- 1.86mmol/L, respectively; mean arterial glucose measured by
      glucometer in the study group and control group were 9.25 +/- 2.05mmol/L and 8.4
      +/- 1.89mmol/L, respectively; and mean arterial glucose measured by blood gas
      analyzer in the study group and control group were 8.41 +/- 1.9mmol/L and 8.24 +/
      1.5mmol/L, respectively. Correlation between capillary values and arterial
      values measured by glucometer was less in the study group (r = 0.936, P < 0.001
      and r = 0.973, P < 0.001). Correlation between capillary values measured by
      glucometer and arterial values measured by blood gas analyzer was also less in
      the study group (r = 0.897, P = 0.001 and r = 0.964, P < 0.001). CONCLUSIONS:
      Capillary blood glucose monitoring is reliable only in a selected group of
      critically ill patients.

PMID- 29173356
TI  - Contrast-Induced Nephropathy After Cardiac Catheterization: Culprits,
      Consequences and Predictors.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is a common complication after
      radiocontrast exposure. METHODS: A retrospective medical record review of 513
      hospitalized patients who underwent cardiac catheterization from June-December
      2014 was done, of which 38 patients with end-stage renal disease and 57 patients
      without preprocedural creatinine were excluded. Serum creatinine concentration
      before the procedure and each day for 3 days after the procedure was recorded.
      CIN was defined as an increase in serum creatinine concentration by >=25% or
      >=0.5mg/dL from the preprocedural value within 72hours of contrast exposure.
      RESULTS: A total of 418 patients (mean age: 69.1 +/- 13.8 years, 55% males) were
      included in the study. Mean incidence of CIN was 3.7% (n = 16). CIN accounted for
      longer duration of hospitalization, lengthier intensive care unit admission,
      requirement of hemodialysis and higher mortality. Incidence of CIN was higher in
      the presence of preexisting atrial fibrillation (AF), congestive heart failure
      (CHF) and chronic kidney disease (CKD). When tested by univariate analysis,
      incidence of CIN was 13.8% in the AF group (P < 0.001), 8.6% in CHF group (P <
      0.01) and 8.9% in CKD group (P < 0.002), compared with 2.3%, 1.9% and 2.4% in the
      absence of preexisting AF, CHF and CKD, respectively. On further testing using
      multivariate logistic regression model using AF, CHF and CKD as independent
      variables, development of CIN was strongly associated with preexisting AF with an
      odds ratio of 4.11, 95% CI: 1.40-12.07, P = 0.01. CONCLUSION: Identifying
      patients at risk is an important step in preventing CIN. Preexisting AF,
      independent of traditional risk factors, may increase the risk for CIN.

PMID- 29173357
TI  - Ischemia Modified Albumin Test to Detect Early Diabetic Complications.
AB  - BACKGROUND: The objective of this study was to assess the albumin cobalt binding
      (ACB) test in a cohort of type 2 diabetes patients. The ACB test is a simple,
      inexpensive, sensitive and robust test that could have important clinical
      application in detecting complications of type 2 diabetes mellitus. MATERIALS AND
      METHODS: We tested patients with type 2 diabetes without any clinically
      detectable complications or without any other comorbid conditions for serum ACB
      levels along with an equal number of age- and sex-matched healthy control
      subjects. ACB levels were compared after the patients with diabetes were
      investigated for various complications using standard statistical tests of
      significance. RESULTS: A total of 100 patients with type 2 diabetes were studied
      with age- and sex-matched healthy control subjects. Of the 100 patients, 78 had
      different complications on detailed laboratory testing. The patients with
      complications had significantly higher ACB test results when compared to the
      patients with diabetes without complications and to that of the control subjects
      (0.62 +/- 0.04, 0.42 +/- 0.07, 0.30 +/- 0.05absorbance units (ABSU)/mL,
      respectively. P < 0.001). All values in diabetics were significantly higher than
      that of controls. CONCLUSIONS: The serum ACB test is a sensitive indicator of
      complications developed in type 2 diabetes mellitus. Patients may be followed up
      with ACB results to detect early complications in this disease.

PMID- 29173358
TI  - Bacterial Etiology of Lower Respiratory Tract Infections and Their Antimicrobial
      Susceptibility.
AB  - BACKGROUND: Lower respiratory tract infection (LRTI) is one of the common major
      health problems in Nigeria causing morbidity and mortality. The study was
      conducted to determine the current trends of bacterial etiology of LRTIs among
      patients who attended the University of Nigeria Teaching Hospital (UNTH) and
      their antimicrobial susceptibility profile with special interest on pandrug
      resistance. MATERIALS AND METHODS: The study was conducted between February 2014
      and June 2016 in the bacteriology laboratory of UNTH. Sputum samples of 954
      patients with suspected LRTIs were received, after obtaining patients' informed
      consent and ethical clearance from the UNTH. The samples were collected and
      processed according to standard laboratory procedures. RESULTS: The mean age of
      the patients was 42.6 +/- 16.8 years. Of the total 954 sputum samples, 431
      (45.2%) were positive for micro-organisms. A single, unique pathogen was
      recovered in 415 patients (96.3%), and 16 (3.7%) were polymicrobial. The most
      predominant single pathogen was Klebsiella pneumoniae, 215 (49.9%), and the most
      prevalent bacterial combination was Klebsiella spp and Pseudomonas aeruginosa, 6
      (1.4%). Antimicrobial susceptibility testing shows that most isolates of K
      pneumoniae were susceptible to imipenem (94.8%). Among the bacteria, Escherichia
      coli (13.3%) ranked highest, followed by P aeruginosa (12.5%), and the least was
      Staphylococcus aureus (2.1%). CONCLUSIONS: Knowledge of the diversity of
      pathogens responsible for LRTIs and their susceptibility patterns to antibiotics,
      as well as antibiotic resistance surveillance, are important in the effective
      management of LRTI with prompt clinical and laboratory diagnosis along with
      appropriate treatment strategies.

PMID- 29173359
TI  - Effectiveness of Bulking Agent (Solesta) Therapy in Fecal Incontinence in
      Patients Refractory to Conventional Therapies.
AB  - BACKGROUND: Fecal incontinence is a problem that imposes considerable
      socioeconomic consequences. Despite many medical therapies, unmet needs remain. A
      new treatment option is a biocompatible bulking agent (Solesta) administered by
      submucosal injection in the distal rectum. The aims of this study are as follows:
      (1) To evaluate the efficacy and safety of this bulking agent in decreasing the
      severity of fecal incontinence (FI) and improving quality of life. (2) To obtain
      objective evidence of changes in anorectal physiology by high-resolution
      anorectal manometry pretreatment and posttreatment. MATERIALS AND METHODS: From
      January 2014 to June 2015, 17 patients who had failed medical therapy for FI
      received stabilized hyaluronate injected submucosally into the rectum under
      direct anoscopic visualization. The treatment was considered successful if
      patients achieved >50% reduction in FI events during monitoring for up to 12
      months. RESULTS: After the first treatment session, 14 patients (82.3%) had a
      successful outcome. The remaining 3 patients received a second therapy 3 months
      later to achieve this result. At last follow-up, 7 of the 17 patients (41%) were
      having no FI events. The remaining patients had reduction in fecal accidents from
      a mean of 6.4/week baseline to 2.8/week during follow-up. CONCLUSIONS:
      Intrarectal injection of stabilized hyaluronate is effective for treating FI in
      patients who had failed standard medical treatments and is technically easy and
      safely performed as an outpatient procedure.

PMID- 29173360
TI  - Combined Assessment of Relaxin and B-Type Natriuretic Peptide Improves Diagnostic
      Value in Patients With Congestive Heart Failure.
AB  - BACKGROUND: To improve the poor prognosis of congestive heart failure (CHF),
      early and accurate diagnosis is necessary. Relaxin is an endogenous
      cardiovascular peptide, and its plasma level is usually increased in patients
      with CHF. In this pilot study, we aimed to determine the diagnostic value of
      relaxin and B-type natriuretic peptide (BNP) in patients with and without CHF.
      MATERIALS AND METHODS: The plasma level of relaxin was measured by enzyme-linked
      immunosorbent assay and plasma level of BNP by fluorescence immunoassay. The area
      under the receiver operating characteristic curve was used to assess the
      diagnostic value of relaxin and BNP. RESULTS: We included 81 patients with
      decompenstated CHF and 36 controls. Plasma levels of relaxin and BNP were both
      higher in CHF patients than in controls. The correlation between plasma levels of
      relaxin and BNP and between relaxin or BNP and cardiac function was nonlinear.
      Relaxin had medium diagnostic value, and BNP had higher value for cardiac
      function and CHF. At a cutoff of 39.76pg/mL relaxin, sensitivity was 82.7%,
      specificity 55.6%, sum of the highest positive predictive value 80.5% and
      negative predictive value 58.8%. Although the diagnostic value was not better for
      relaxin than BNP, their combined assessment improved the sensitivity and
      specificity of diagnosis for CHF as compared with BNP alone. CONCLUSIONS:
      Combined assessment of relaxin and BNP may improve the diagnosis of decompensated
      CHF, which may have potential application in the clinic.

PMID- 29173361
TI  - Eosinophilic Myocarditis.
AB  - Persistent eosinophilia can cause cardiac tissue damage, typically in the form of
      eosinophilic myocarditis, whether the underlying cause is reactive, a clonal
      myeloid disorder, or idiopathic hypereosinophilic syndrome (HES). Eosinophilic
      myocarditis ranges from mild localized disease to multifocal widespread
      infiltrates associated with myocardial necrosis, thrombotic complications and
      endomyocardial fibrosis. Systemic treatment varies widely depending on the
      underlying cause, so thorough investigation and precise diagnosis are essential.
      Evaluation includes assessment for reactive causes of eosinophilia (vasculitis
      such as eosinophilic granulomatosis and polyangiitis or Churg-Strauss, parasitic
      infection, autoimmune disease, immunoglobulinG4-related disease, medications and
      other causes), genetic lesions characteristic of clonal myeloid disorders
      (platelet-derived growth factor receptor-alpha, platelet-derived growth factor
      receptor-beta and fibroblast growth factor receptor 1) and flow cytometry and
      molecular studies for the aberrant T cells characteristic of lymphocyte-variant
      HES . Patients with reactive eosinophilia require treatment for the underlying
      cause, such as antiparasitic therapy for helminthic infection or
      immunosuppression for eosinophilic granulomatosis and polyangiitis or Churg
      Strauss. Those with a myeloid clone often benefit from the tyrosine kinase
      inhibitor imatinib. Steroids are the first-line treatment for idiopathic HES and
      lymphocyte-variant HES, and hydroxyurea or (pegylated) interferon-alpha may be
      used for relapsed or refractory disease. Mepolizumab, an anti-interleukin-5
      monoclonal antibody, is an effective steroid-sparing agent in HES but is not
      widely available for this indication.

PMID- 29173362
TI  - Propofol Potentiates Sevoflurane-Induced Inhibition of Nuclear Factor--kappaB
      Mediated Inflammatory Responses and Regulation of Mitogen-Activated Protein
      Kinases Pathways via Toll-like Receptor 4 Signaling in Lipopolysaccharide-Induced
      Acute Lung Injury in Mice.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4)-induced initiation of mitogen-activated
      protein kinases and the nuclear factor-kappa B signaling cascade is reportedly
      involved in inflammatory responses during lung injury. Studies have found that
      volatile anesthetics, such as isoflurane and sevoflurane, inhibit inflammation.
      This investigation explored the protective effects of propofol and whether
      propofol potentiates the protective effects of sevoflurane against
      lipopolysaccharide (LPS)-induced acute lung injury. MATERIALS AND METHODS: Male
      BALB/c mice were treated with LPS (10MUg/mouse; intranasal instillation) to
      induce acute lung injury. Mice were exposed to sevoflurane (3%; 6 hours) alone or
      combined with propofol (10 or 20mg/kg body weight; subcutaneously) followed by
      sevoflurane for 1 hour before the LPS challenge. RESULTS: Sevoflurane with or
      without propofol attenuated pulmonary edema, restored altered lung architecture
      and reduced influx of inflammatory cells into bronchoalveolar lavage fluid after
      the LPS challenge. LPS-mediated overproduction of the proinflammatory cytokines
      tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 as well as
      nitric oxide, were reduced. Sevoflurane either alone or with propofol
      downregulated TLR4 and TLR4-mediated mitogen-activated protein kinase and nuclear
      factor-kappa B signaling. CONCLUSIONS: Combined exposure to propofol and
      sevoflurane was more effective than sevoflurane administered alone, suggesting
      the positive effects of propofol on sevoflurane-mediated anti-inflammatory
      effects.

PMID- 29173363
TI  - Novel Survivin-Targeted Small Interfering RNA Delivered by Nanoparticles.
AB  - BACKGROUND: The aim of the present study was to investigate the antitumor effect
      of our novel survivin-targeted small interfering RNA (siRNA) nanoliposomes on
      xenograft mouse models with human cervical carcinoma HeLa cells, and to evaluate
      pharmacokinetics. MATERIALS AND METHODS: siRNA nanoliposome was prepared and
      transfected into xenograft mouse models. Tumor growth in mice was determined and
      survivin expression was analyzed by using histologic and immunohischemical
      staining. Furthermore, low, moderate and high doses of survivin siRNA
      nanoliposomes were injected in 3 groups, and plasma concentrations were detected
      at various time points by reverse transcription quantitative polymerase chain
      reaction. Biodistribution of siRNA in tumor and other important organs were also
      determined. RESULTS: Survivin expression was significantly downregulated by
      survivin siRNA delivery mediated by nanoliposome, along with significant
      suppression of cell growth. Peak concentrations were obtained at 15 minutes after
      injection in each group, with 1,042,538.00, 6,837,099.54 and 14,631,333.15pg/mL,
      respectively, and the plasma concentration decreased significantly after 24
      hours. The half-time life of survivin siRNA nanoliposomes in each group was 3.60,
      2.64 and 2.80 hours, respectively. The area under curve values were 952,190.88,
      6,800,687.79 and 13,803,680.96h/pg/mL, and the total drug clearance were
      1,050.12, 441.13 and 434.67mL/h/kg. A significant accumulation of Cy5-labeled
      siRNA was found in the tumor, and a nonspecific accumulation was reduced
      significantly in lung. CONCLUSIONS: Our findings revealed that survivin
      suppression by siRNA may contribute to tumor inhibition through both
      proliferation inhibition and apoptosis promotion effect, and the pharmacokinetic
      characteristics serve as a fundamental role for further studies on its
      applicability for cancer therapy.

PMID- 29173364
TI  - Painless Aortic Dissection.
AB  - Painless aortic dissection (PAoD) has been previously linked to poor outcomes. We
      recently encountered a case of a patient with PAoD presenting with dyspnea; the
      clue to diagnosis was the presence of a loud aortic diastolic murmur. A
      systematic review of the literature revealed 86 other cases, 62% of which
      occurred in men with a mean age of 65 years. Left-sided neurologic deficits were
      the most common presentation, followed by dyspnea and bilateral lower extremity
      deficits. Pulse asymmetry was found in 53% of patients, as 29% had right-left
      asymmetry and 24% had upper-lower asymmetry. Cumulatively, 88% of the cases were
      type A dissection and 51% of the patients died. Erroneous application of
      fibrinolysis and anticoagulation occurred in multiple instances. PAoD is rare but
      potentially fatal; a high index of suspicion and a thorough cardiovascular
      examination are needed to establish the diagnosis before applying possible
      harmful interventions such as fibrinolysis, vasodilation or anticoagulation.

PMID- 29173365
TI  - Actinomyces Peritonitis: A Unique Therapy.

PMID- 29173366
TI  - Synovial Sarcoma With Intracranial Metastasis as the Site of Reoccurrence.

PMID- 29173367
TI  - Uremic Leontiasis Ossea.

PMID- 29173368
TI  - Broken Heart, Indomitable Spirit: De Oppresso Liber.

PMID- 29173369
TI  - Anal Fistulas Due to Pseudomyxoma Anorectum.

PMID- 29173370
TI  - Exercise as antidepressant treatment: Time for the transition from trials to
      clinic?

PMID- 29173371
TI  - Embrace Action: Use Holidays to Strengthen Social Bonds.

PMID- 29173372
TI  - Partnering With Perioperative Colleagues to Prevent Infection.

PMID- 29173373
TI  - Results of the 2017 AORN Salary and Compensation Survey.
AB  - AORN conducted its 15th annual compensation survey for perioperative nurses in
      June 2017. A multiple regression model was used to examine how several variables,
      including job title, educational level, certification, experience, and geographic
      region, affect nurse compensation. Comparisons between the 2017 data and data
      from previous years are presented. The effects of other forms of compensation
      (eg, on-call compensation, overtime, bonuses, shift differentials, benefits) on
      base compensation rates are examined. Additional analyses explore the current
      state of the nursing shortage and the sources of job satisfaction and
      dissatisfaction.

PMID- 29173374
TI  - Minimizing Sources of Airborne, Aerosolized, and Contact Contaminants in the OR
      Environment.
AB  - Surgical site infections are unintended consequences of surgery that can cause
      harm to patients and place financial burdens on health care organizations.
      Extrinsic factors in the OR-including health care providers' behavior and
      practices that modify air movement, the physical environment, equipment, or
      surgical instruments-can increase microbial contamination. Microbes can be
      transported into the surgical incision by airborne or contact routes and
      contribute to a surgical site infection. Simple practices to prevent infection
      such as minimizing airborne particles and contaminants, maintaining equipment
      according to the manufacturer's recommendations, cleaning and disinfecting the
      environment and surgical instruments, and performing proper hand hygiene-can
      reduce the degree of microbial contamination. Perioperative leaders and health
      care providers can help decrease the patient's risk of surgical site infection
      with proactive preventive practices that break the chain of infection.

PMID- 29173375
TI  - Operation Clean Air: Implementing a Surgical Smoke Evacuation Program.
AB  - Surgical smoke is a hazardous byproduct of any surgery involving a laser or an
      electrosurgical unit. Although research and professional organizations identified
      surgical smoke as harmful many years ago, this byproduct continues to be a safety
      hazard in the OR. An interdisciplinary team at a large academic medical center
      sought to address the exposure of patients and perioperative team members to
      surgical smoke. The team used the nursing process to resolve the lack of smoke
      evacuator equipment and surgical smoke staff member knowledge. To increase
      awareness of the hazards of surgical smoke, we gave presentations to nursing
      staff members and surgeons, who then completed educational modules. We conducted
      audits in all ORs to monitor compliance. The use of smoke evacuation supplies has
      more than quadrupled since education began. Additional unit-based education
      continues every day and is a constant reminder that safety is the responsibility
      of all perioperative team members.

PMID- 29173376
TI  - Evaluation of a Brief Team Training Intervention in Surgery: A Mixed-Methods
      Study.
AB  - The aim of this study was to evaluate a brief team training program in relation
      to teams' observed nontechnical skills (NTSs) in surgery, teams' perceptions of
      safety culture, and the training implementation. We used mixed methods to analyze
      structured observations of 179 surgeries, semistructured interviews with surgical
      team members from four selected surgical specialties, and a survey. There were
      significant (P < .001) improvements in surgical teams' observed NTSs and in the
      use of the World Health Organization's Surgical Safety Checklist after
      participation in the training program. Nonsignificant results included increased
      perceived safety climate and decreased perceived teamwork climate. From
      participant interviews, we identified that production pressure and time
      constraints were the biggest barriers to implementation and the greatest enabler
      was the organization's support for staff education initiatives. Most participants
      perceived the content of the program to be useful. These results highlight the
      complexities inherent in the development and evaluation of interdisciplinary
      patient safety interventions.

PMID- 29173377
TI  - Navigating Nursing Education.
AB  - All nurses must embrace lifelong learning and engage in academic progression to
      help transform health care. This article explores the various forms of nursing
      education and focuses on the types of degrees available, different practice roles
      and pathways, types of educational institutions and programs, and accreditation
      and its governing bodies. The benefits to nurses who pursue additional education
      include career mobility, additional responsibilities, and personal satisfaction.
      The benefits to patients include receiving the most current evidence-based care
      from a more highly educated and competent workforce.

PMID- 29173378
TI  - Health Care Workers' Use and Cleaning of X-Ray Aprons and Thyroid Shields.
AB  - We evaluated the use and cleaning of x-ray aprons and thyroid shields by
      surveying rural hospital system health care workers who wear x-ray aprons and
      thyroid shields. One hundred fifty-five of the 173 respondents were RNs (89.6%),
      and 94 respondents were from inpatient or outpatient surgical settings (54.3%).
      One hundred thirty-five respondents (78.0%) reported soiled x-ray aprons or
      thyroid shields, and 52 (30.1%) reported shield odors. Eighty-three participants
      (48.0%) indicated they never spot cleaned. Standard department cleaning never
      occurred for 37 x-ray aprons or thyroid shields (21.4%); and 114 x-ray aprons or
      thyroid shields (65.9%) contacted a patient or patient item 1 to 10 times per
      shift. Twenty-six participants (15%) specified there were policies and procedures
      for cleaning x-ray aprons and thyroid shields. Use of evidence-based cleaning
      guidelines and manufacturer's requirements for effective spot and standard
      cleaning of the protective aprons and thyroid shields are warranted.

PMID- 29173379
TI  - Clinical Ethics: Patient and Provider Safety.

PMID- 29173380
TI  - Clinical Issues-December 2017.
AB  - Bed bugs Key words: bed bugs, pest management, infestation, transmission. Warming
      irrigation fluids Key words: irrigation fluid, warming fluid, hypothermia,
      warming cabinet. Fasting before surgery Key words: fasting, NPO, liquids, solids.
      Advanced cardiac life support requirements for perioperative nurses Key words:
      advanced cardiac life support, ACLS certification, pediatric advanced life
      support, PALS certification, basic life support.

PMID- 29173381
TI  - Evidence appraisal of Erestam S, Haglind E, Bock D, Andersson AE, Angenete E.
      Changes in safety climate and teamwork in the operating room after implementation
      of a revised WHO checklist: a prospective interventional study.: Patient Saf
      Surg. 2017;11:4. doi:10.1186/s13037-017-0120-6.

PMID- 29173382
TI  - Guideline at a Glance: Energy-Generating Devices.

PMID- 29173383
TI  - Falling Through the Crack (in the Bedrails).

PMID- 29173384
TI  - Life's defining moment: Christiaan Barnard and the first human heart transplant.

PMID- 29173385
TI  - Conquering the first hurdles in cardiac transplantation: In the footprints of
      giants.

PMID- 29173386
TI  - The dark early years of heart transplantation: Some lessons learned.

PMID- 29173387
TI  - Evolutionary perspective of mechanical circulatory support as a bridge to heart
      transplantation.

PMID- 29173388
TI  - Clinical trials in heart transplantation: The evolution of evidence in
      immunosuppression.

PMID- 29173389
TI  - The scourge and enigmatic journey of cardiac allograft vasculopathy.

PMID- 29173390
TI  - Insurance coverage of heart transplantation in the United States: The dilemma,
      the debate and the definitive decision that ultimately determined the future of
      transplantation.

PMID- 29173392
TI  - The role of nurses in understanding and enhancing quality of life: A journey from
      advanced heart failure to heart transplantation.

PMID- 29173391
TI  - Advances in the immunology of heart transplantation.

PMID- 29173393
TI  - The life and the legacy of Hamilton Naki: Experimental heart transplant surgeon
      and teacher.

PMID- 29173395
TI  - Challenges, diligence, and a breakthrough in donation after circulatory death in
      heart transplantation.

PMID- 29173394
TI  - Outcome after heart transplantation from donation after circulatory-determined
      death donors.
AB  - BACKGROUND: The requirement for heart transplantation is increasing, vastly
      outgrowing the supply of hearts available from donation after brain death (DBD)
      donors. Transplanting hearts after donation after circulatory-determined death
      (DCD) may be a viable additive alternative to DBD donors. This study compared
      outcomes from the largest single-center experience of DCD heart transplantation
      against matched DBD heart transplants. METHODS: DCD hearts were retrieved using
      normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP).
      During NRP, perfusion was restored to the arrested heart within the donor with
      the exclusion of the cerebral circulation, whereas DPP hearts were removed
      directly. All hearts were maintained on machine perfusion during transportation.
      A retrospective cohort of DBD heart transplants, matched for donor and recipient
      characteristics, was used as a comparison group. The primary outcome measure of
      this study (set by the United Kingdom regulatory body) was 90-day survival.
      RESULTS: There were 28 DCD heart transplants performed during the 25-month study
      period. Survival at 90 days was not significantly different between DCD and
      matched DBD transplant recipients (DCD, 92%; DBD, 96%; p = 1.0). Hospital length
      of stay, treated rejection episodes, allograft function, and 1-year survival
      (DCD, 86%; DBD, 88%; p = 0.98) were comparable between groups. The method of
      retrieval (NRP or DPP) was not associated with a difference in outcome.
      CONCLUSIONS: These results suggest that heart transplantation from DCD heart
      donation provides comparable short-term outcomes to traditional DBD heart
      transplants and can serve to increase heart transplant activity in well-selected
      patients.

PMID- 29173396
TI  - [The ear: This organ with two senses!]

PMID- 29173397
TI  - Global impact of radiotherapy in oncology: Saving one million lives by 2035.

PMID- 29173398
TI  - Sudden Cardiac Death: Interface Between Pathophysiology and Epidemiology.
AB  - The population incidence of sudden cardiac arrest (SCA) and sudden cardiac death
      have not changed appreciably during the decades of improvement in general
      outcomes from cardiovascular diseases, but the age, clinical circumstances, and
      pathophysiologic mechanisms have. The epidemiology and pathophysiology of SCA are
      linked, in that mechanisms of SCA can be modeled based on substrate and
      expression characteristics. The goal for the future is to expand pathophysiologic
      and epidemiologic interactions to achieve strong individual risk prediction, to
      complement the limits of application of population risk data to individuals.

PMID- 29173399
TI  - Basic Electrophysiologic Mechanisms of Sudden Cardiac Death Caused by Acute
      Myocardial Ischemia and Infarction.
AB  - Sudden cardiac death caused by acute ischemia results from electrophysiologic
      changes in myocardium deprived of its blood supply. These changes include a
      reduction in resting potential and phase 0 depolarization and an increase in
      intercellular resistivity that slow conduction, cause conduction block, and lead
      to reentrant excitation and ventricular fibrillation. Reperfusion of a coronary
      artery after a short period of occlusion leads to similar changes.

PMID- 29173400
TI  - Channelopathies as Causes of Sudden Cardiac Death.
AB  - This article reviews the main clinical aspects of 3 channelopathies: the long QT
      syndrome, the catecholaminergic polymorphic ventricular tachycardia, and the
      Brugada syndrome. The text summarizes our views on clinical presentation and
      diagnosis, on risk stratification, and on therapy. Special attention is given to
      the progress in the understanding of the genetic bases and on the growing impact
      of genetics on therapy, which, at least in the case of long QT syndrome, now
      allows gene-specific management.

PMID- 29173401
TI  - Public Access Defibrillation: Is This Making Any Difference? Controversial Issues
      in Resuscitation from Cardiac Arrest.
AB  - Public access defibrillation is particularly valuable in witnessed cardiac
      arrests that occur in public places. Bystander and police use of automated
      external defibrillators (AEDs) has increased over the past 15 years, resulting in
      improved survival with normal or near-normal neurologic function. There is great
      promise for increasing bystander use of defibrillators as the technology is
      applied to linking patients with shockable arrests to volunteers committed to
      bringing AEDs to the patients. There continues to be controversy as to the value
      of epinephrine, antiarrhythmic drugs, hypothermia, and mechanical chest
      compression in resuscitative efforts.

PMID- 29173402
TI  - Sudden Cardiac Death During Sports Activities in the General Population.
AB  - Regular exercise reduces cardiovascular and overall mortality. Participation in
      sports is an important determinant of cardiovascular health and fitness. Regular
      sports activity is associated with a smaller risk of sudden cardiac death (SCD).
      However, there is a small risk of sports-related SCD. Sports-related SCD accounts
      for approximately 5% of total SCD. SCD among athletes comprises only a fraction
      of all sports-related SCD. Sport-related SCD has a male predominance and an
      average age of affliction of 45 to 50 years. Survival is better than for other
      SCD. This review summarizes links between sports and SCD and discusses current
      knowledge and controversies.

PMID- 29173403
TI  - Sudden Cardiac Death in Children and Adolescents.
AB  - Sudden cardiac death (SCD) is a rare but devastating event in children and
      adolescents. Etiologies include congenital heart disease, cardiomyopathies,
      primary arrhythmia syndromes, and miscellaneous conditions. Challenges in the
      diagnosis and prevention of SCD in the young are reviewed.

PMID- 29173404
TI  - Sudden Cardiac Death in Genetic Cardiomyopathies.
AB  - Sudden cardiac death (SCD) caused by ventricular arrhythmias is common in
      patients with genetic cardiomyopathies (CMs) including dilated CM, hypertrophic
      CM, and arrhythmogenic right ventricular CM (ARVC). Phenotypic features can
      identify individuals at high enough risk to warrant placement of an implantable
      cardioverter-defibrillator, although risk stratification schemes remain
      imperfect. Genetic testing is valuable for family cascade screening but with few
      exceptions (eg, LMNA mutations) do not identify higher risk for SCD. Although
      randomized trials are lacking, observational data suggest that ICDs can be
      beneficial. Vigorous exercise can exacerbate ARVC disease progression and
      increase likelihood of ventricular arrhythmias.

PMID- 29173405
TI  - Electrocardiographic Markers of Sudden Cardiac Death (Including Left Ventricular
      Hypertrophy).
AB  - Although the electrocardiograph (ECG) was invented more than 100 years ago, it
      remains the most commonly used test in clinical medicine. It is easy to perform,
      relatively cheap, and results are readily available. Interpretation, however,
      needs expertise and knowledge. New data, phenomenon, and syndromes are
      continually discovered by the ECG. It is important to differentiate between
      normal and abnormal ECGs first and then try to correlate the findings with
      clinical pathologies. Furthermore, the ECG is an integral part of the screening
      model for a variety of conditions such as channelopathies, athletes, preoperative
      risk profile, and remains the cardiologist's best friend.

PMID- 29173406
TI  - Prediction and Prevention of Sudden Cardiac Death.
AB  - Sudden death is a major problem, with significant impact on public health. Many
      conditions predispose to sudden cardiac death and sudden cardiac arrest (SCA),
      foremost among them coronary artery disease, and an effective therapy exists in
      the form of the implantable cardioverter defibrillator. Risk stratification for
      SCA remains imperfect, especially for patients with nonischemic cardiomyopathy.
      Ongoing trials may make it easier to identify those at high risk, and potentially
      those at very low risk, in the future.

PMID- 29173407
TI  - Role of Cardiac Imaging in Evaluating Risk for Sudden Cardiac Death.
AB  - Sudden cardiac death (SCD) is a major cause of death from cardiovascular disease.
      Our ability to predict patients at the highest risk of developing lethal
      ventricular arrhythmias remains limited. Despite recent studies evaluating risk
      stratification tools, there is no optimal strategy. Cardiac imaging provides the
      opportunity to assess left ventricular ejection fraction, strain, fibrosis, and
      sympathetic innervation, all of which are pathophysiologically related to SCD
      risk. These modalities may play a role in the identification of vulnerable
      anatomic substrates that provide the pathophysiologic basis for SCD. Further
      studies are required to identify optimal imaging platform for risk assessment.

PMID- 29173408
TI  - Biomarkers to Predict Cardiovascular Death.
AB  - This article reviews biomarkers that have been shown to identify subjects at
      increased risk for cardiovascular death within the general population, in those
      with established coronary artery disease, and in those with heart failure. Use of
      biomarkers for risk stratification for sudden cardiac death continues to evolve.
      It seems that a multimarker strategy for risk stratification using simple
      measures of circulating proteins and usual clinical risk factors, particularly in
      patients with known coronary artery disease, can be used to identify patients at
      near-term risk of death. Whether similar strategies in the general population
      will prove to be cost-effective needs to be investigated.

PMID- 29173410
TI  - Sudden Cardiac Death in Ischemic Heart Disease: Pathophysiology and Risk
      Stratification.
AB  - Sudden cardiac death (SCD) accounts for approximately 360,000 deaths annually in
      the United States. Ischemic heart disease is the major cause of death in the
      general adult population. SCD can be due to arrhythmic or nonarrhythmic cardiac
      causes. Arrhythmic SCD may be caused by ventricular tachyarrhythmia or pulseless
      electrical activity/asystole. This article reviews the most recent
      pathophysiology and risk stratification strategies for SCD, emphasizing
      electrophysiologic surrogates of conduction disorder, dispersion of
      repolarization, and autonomic imbalance. Factors that modify arrhythmic death are
      addressed.

PMID- 29173411
TI  - Ventricular Arrhythmias and Sudden Cardiac Death.
AB  - Ventricular arrhythmias remain a significant cause of sudden cardiac death (SCD),
      and knowledge of their cause and high-risk features is important. SCD occurs when
      the interaction between vulnerable substrates and acute triggers results in
      sustained ventricular tachycardia progressing to ventricular fibrillation. Here,
      the authors aim to review the role of ventricular arrhythmias in SCD, first by
      approaching the substrates that support ventricular arrhythmias, and then by
      exploring features of these substrates and the acute triggers that may lead to
      SCD.

PMID- 29173412
TI  - Heart Failure and Sudden Cardiac Death.
AB  - The Centers for Diseases Control and Prevention estimates that 5.7 million adults
      in the United States suffer from heart failure and 1 in 9 deaths in 2009 cited
      heart failure as a contributing cause. Almost 50% of patients who are diagnosed
      with heart failure die within 5 years of diagnosis. Cardiovascular disease is a
      public health burden. The prognosis of patients with heart failure has improved
      significantly. However, the risk for death remains high. Managing sudden death
      risk and intervening appropriately with primary or secondary prevention
      strategies are of paramount importance.

PMID- 29173409
TI  - Cardiac Innervation and the Autonomic Nervous System in Sudden Cardiac Death.
AB  - Neural remodeling in the autonomic nervous system contributes to sudden cardiac
      death. The fabric of cardiac excitability and propagation is controlled by
      autonomic innervation. Heart disease predisposes to malignant ventricular
      arrhythmias by causing neural remodeling at the level of the myocardium, the
      intrinsic cardiac ganglia, extracardiac intrathoracic sympathetic ganglia,
      extrathoracic ganglia, spinal cord, and the brainstem, as well as the higher
      centers and the cortex. Therapeutic strategies at each of these levels aim to
      restore the balance between the sympathetic and parasympathetic branches.
      Understanding this complex neural network will provide important therapeutic
      insights into the treatment of sudden cardiac death.

PMID- 29173413
TI  - Sudden Cardiac Death in Acute Coronary Syndromes.
AB  - Sudden cardiac death in acute coronary syndromes mostly results from complex
      ventricular arrhythmias. Although the incidence has fallen with contemporary
      management, they still pose a threat for many patients. Treatment consists of
      immediate termination by electrical cardioversion and prompt coronary
      revascularization for relief of ischemia. Beta-blockers administered
      prophylactically have a protective effect. For recurrent episodes, pharmacologic
      treatment consists of beta-blockers and amiodarone, or, in nonresponsive
      patients, lidocaine. Other antiarrhythmic drugs play only a marginal role.
      Catheter ablation performed in qualified centers can be effective in recurrent
      episodes of ventricular tachycardia or ventricular fibrillation triggered by
      premature ventricular contractions.

PMID- 29173414
TI  - Neuromuscular Disease: Cardiac Manifestations and Sudden Death Risk.
AB  - Cardiovascular complications of neuromuscular diseases disproportionately affect
      the cardiac conduction system. Cardiomyopathy and cardiac arrhythmias produce
      significant morbidity and mortality. Patients with neuromuscular diseases should
      be carefully and frequently evaluated for the presence of bradycardia, heart
      block, and tachyarrhythmias. Preemptive treatment with permanent pacemakers or
      implanted defibrillators is appropriate in patients with conduction system
      disease or who are at risk for ventricular arrhythmias.

PMID- 29173415
TI  - Sudden Cardiac Death: Lessons Learned from Cardiac Implantable Rhythm Devices.
AB  - Trials have demonstrated that implantable-cardioverter defibrillators (ICDs) are
      effective in preventing sudden cardiac death (SCD). The degree of left
      ventricular dysfunction is the only parameter to identify primary prevention
      populations at higher risk of SCD in which ICDs may reduce longitudinal mortality
      risk. Clinical application of current stratification approaches based on left
      ventricular ejection fraction (LVEF) alone has failed to prevent most SCD in the
      general population. This lack of specificity has resulted in a significant number
      of potentially unnecessary ICDs. Future studies should focus on newer risk
      markers to improve the predictive value of LVEF and SCD prevention.

PMID- 29173416
TI  - Primary Prevention Implantable Cardiac Defibrillator Trials: What Have We
      Learned?
AB  - Patients with impaired left ventricular systolic function frequently die suddenly
      because of arrhythmic and nonarrhythmic causes. Nine trials have evaluated the
      utility of implantable cardioverter-defibrillator (ICDs) primary prevention of
      sudden cardiac death. Individuals with stable ischemic heart disease (no recent
      myocardial infarction), especially those with inducible arrhythmias, seem to
      derive the highest mortality benefit from prophylactic ICD use. The role of ICDs
      in other patient populations is much less clear and may even be harmful. The use
      of antiarrhythmic medications has not been shown to improve survival in any
      patient population at risk for sudden death.

PMID- 29173417
TI  - The Subcutaneous Defibrillator.
AB  - The transvenous implantable cardioverter-defibrillator (ICD) has been shown in
      multiple studies to be effective in the prevention of sudden cardiac death in
      select populations. The Achilles heel of traditional ICD technology has been the
      transvenous lead. The subcutaneous ICD provides effective sudden death protection
      while avoiding lead-related complications of traditional transvenous systems. The
      subcutaneous ICD is a reasonable option for patients with an ICD indication who
      do not need bradycardia pacing or cardiac resynchronization therapy.

PMID- 29173418
TI  - Future Directions: Management of Sudden Cardiac Death.
AB  - There will always be a need to optimize early recognition and treatment of sudden
      cardiac arrest. For out-of-hospital cardiac arrest, this requires a complex
      system of care involving bystanders, 911 dispatchers, and emergency medical
      service and hospital-based providers. Optimizing this system is fundamental to
      improving outcomes. In addition, personnel and resources are needed to develop
      and sustain a research pipeline that will bring new scientific discoveries and
      technologies to the field. The 2015 Institute of Medicine report, "Strategies to
      Improve Cardiac Arrest Survival: A Time to Act," provides a roadmap.

PMID- 29173419
TI  - Sudden Cardiac Death: Back to the Future.

PMID- 29173420
TI  - Sudden Cardiac Death: Contemporary Challenges.

PMID- 29173421
TI  - Epidemiology and Overview of the Clinical Spectrum of Degenerative Cervical
      Myelopathy.
AB  - Degenerative cervical spondylosis (DCM) is an umbrella term used to describe
      myelopathy caused by various degenerative changes in the cervical spine. This
      article outlines the spectrum of DCM and reviews the epidemiology of each factor
      composing DCM. The uniform term of DCM is expected to elucidate the epidemiology
      of myelopathy caused by degenerative changes of the cervical spine."

PMID- 29173422
TI  - History and Evolution of Laminoplasty.
AB  - Techniques of expansive laminoplasty for degenerative cervical myelopathy and
      ossified posterior longitudinal ligament are described, focusing on the history
      of the surgical procedure. Laminectomy was the only approach for posterior
      decompression before Japanese orthopedic surgeons introduced laminoplasty from
      the 1970s to the 1980s to overcome the poor outcomes of laminectomy. Recent
      laminoplasty techniques offer less invasive maneuvers to the posterior cervical
      muscle structures to reduce axial neck pain and to obtain better functional
      outcome, but every operation is carried out based on the unchanged initial
      concept. Some recent attempts to improve the surgical results are also discussed.

PMID- 29173423
TI  - Significant Predictors of Outcome Following Surgery for the Treatment of
      Degenerative Cervical Myelopathy: A Systematic Review of the Literature.
AB  - This systematic review aims to summarize important clinical predictors of
      outcomes in patients undergoing surgery for the treatment of degenerative
      cervical myelopathy. Based on the results of this article, patients with a longer
      duration of symptoms and more severe myelopathy are likely to have worse surgical
      outcomes. With respect to age, several studies have indicated that elderly
      patients are less likely to translate neurologic recovery into functional
      improvements. However, many other studies have failed to identify a significant
      association between age and outcomes. Finally, smoking status and presence of
      comorbidities may be important predictors of outcomes.

PMID- 29173424
TI  - Neurologic Complications in Managing Degenerative Cervical Myelopathy:
      Pathogenesis, Prevention, and Management.
AB  - Degenerative cervical myelopathy is a common neurologic condition induced by
      compression of the spinal cord due to degenerative changes of the cervical spine.
      It is one of the leading causes of acquired disability in adults and manifests as
      a slow deterioration of the symptoms in a majority of the patients. A variety of
      nonsurgical and surgical treatments have been performed to ameliorate or halt the
      symptoms, and a number of articles describe their methods, efficacy, and
      complications. In this article, the pathogenesis, prevention, and management of
      the neurologic complications are reviewed.

PMID- 29173425
TI  - Pathobiology of Degenerative Cervical Myelopathy.
AB  - Degenerative cervical myelopathy (DCM) is a common spinal cord disease caused by
      chronic mechanical compression of the spinal cord. The mechanism by which
      mechanical stress results in spinal cord injury is poorly understood. The most
      common mechanisms involved in the pathobiology of DCM include apoptosis,
      inflammation, and vascular changes leading to loss of neurons, axonal
      degeneration, and myelin changes. However, the exact pathophysiologic mechanisms
      of DCM are unclear. A better understanding of the pathogenesis of DCM is required
      for the development of treatments to improve outcomes. This review highlights the
      mechanisms of injury and pathology in DCM.

PMID- 29173426
TI  - Options of Management of the Patient with Mild Degenerative Cervical Myelopathy.
AB  - Surgical management of patients with mild degenerative cervical myelopathy (DCM)
      is controversial. This article reviews 84 subjects with cervical spondylotic
      myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL)
      who underwent surgical treatment. Nine had mild myelopathy: 6 CSM and 3 OPLL.
      Seven presented with pain or numbness of upper extremities. MRI revealed
      intramedullary hyperintensity in 55.6%. Five underwent anterior decompression and
      fusion, whereas 4 were operated posteriorly. Pain and intramedullary signal
      change on MRI are important. Management of patients with mild DCM should be
      determined individually, considering benefits and risks in long-term conservative
      treatment and surgery.

PMID- 29173427
TI  - Management of the Patient with Cervical Cord Compression but no Evidence of
      Myelopathy: What Should We do?
AB  - Degenerative cervical myelopathy (DCM) eventually affects not only activities of
      daily living but also quality of life. DCM is usually a gradually progressive,
      sometimes irreversible, disease of the cervical spinal cord, although there is
      always a risk of acute deterioration caused by minor trauma. There is still not
      enough evidence regarding the prognosis of mild DCM without surgical treatment,
      and conservative treatment seems a reasonable option, although patients need to
      be followed closely because some do deteriorate over time. Surgeons need to
      understand, however, the importance of decision making in the surgical management
      of mild DCM.

PMID- 29173428
TI  - Clinical Characteristics and Management of C3-4 Degenerative Cervical Myelopathy.
AB  - Single-level anterior cervical discectomy and fusion (ACDF) was performed at C3
      4; non-C3-4 ACDF patients of the authors' random sample of ACDF patients were
      compared with C3-4 ACDF patients. The radiological study of C3-4 ACDF patients
      shows that they had significant cervical lordosis, and cervical motion was
      dependent on the C3-4 segment, which accounted for 39.8% of C2-7 range of
      intervertebral motion (total motion). In C3-4 ACDF patients, not only static
      factors but also dynamic factors (instability) at the C3-4 level contributed to
      the major causes of degenerative cervical myelopathy.

PMID- 29173429
TI  - Intraoperative Neurophysiologic Monitoring for Degenerative Cervical Myelopathy.
AB  - Multimodal intraoperative neurophysiologic monitoring is a reliable tool for
      detecting intraoperative spine injury and is recommended during surgery for
      degenerative cervical myopathy (DCM). Somatosensory evoked potential (SEP) can be
      used to monitor spine and peripheral nerve injury during positioning in surgery
      for DCM. Compensation technique for transcranial evoked muscle action potentials
      (tcMEPs) should be adopted in intraoperative monitoring during surgery for DCM.
      Free-running electromyography is a useful real-time monitoring add-on modality in
      addition to SEP and tcMEP.

PMID- 29173430
TI  - Health Economics and the Management of Degenerative Cervical Myelopathy.
AB  - Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord
      impairment worldwide. Surgical intervention has been demonstrated to be effective
      and is becoming standard of care. Spine surgery, however, is costly and value
      needs to be demonstrated. This review serves to summarize the key health economic
      concepts as they relate to the assessment of the value of surgery for DCM. This
      is followed by a discussion of current health economic research on DCM, which
      suggests that surgery is likely to be cost effective. The review concludes with a
      summary of future questions that remain unanswered, such as which patient
      subgroups derive the most value from surgery and which surgical approaches are
      the most cost effective.

PMID- 29173431
TI  - Managing the Complex Patient with Degenerative Cervical Myelopathy: How to Handle
      the Aging Spine, the Obese Patient, and Individuals with Medical Comorbidities.
AB  - Degenerative cervical myelopathy (DCM) is the most common cause of nontraumatic
      spinal cord injury worldwide. Even relatively mild impairment in functional
      scores can significantly impact daily activities. Surgery is an effective
      treatment for DCM, but outcomes are dependent on more than technique and
      preoperative neurologic deficits.

PMID- 29173432
TI  - Future Directions and New Technologies for the Management of Degenerative
      Cervical Myelopathy.
AB  - The diagnosis and treatment of degenerative cervical myelopathy (DCM) has been
      evolving over the past 5 decades as a result of collaborations between clinicians
      and scientists. The most recent trends in basic and clinical research include
      advances in imaging, clinical diagnostic tools, molecular genetics, surgical
      techniques, and reparative/regenerative strategies. Spine surgeons are witnessing
      a fast-paced evolution, which is reshaping the management strategies available
      for an aging population that suffers increasingly from this degenerative
      condition.

PMID- 29173433
TI  - The Natural History of Degenerative Cervical Myelopathy.
AB  - Despite being the leading cause of spinal cord dysfunction among adults
      worldwide, little is known about the natural history of degenerative cervical
      myelopathy (DCM). There is mounting evidence of the effectiveness of surgery for
      DCM in halting progression of symptoms, and in fact, in improving neurologic
      outcomes, functional status, and quality of life. However, surgical decision
      making relies on a weighing of the risks and benefits of alternative strategies.
      We reviewed the available literature pertaining to the natural course of DCM and
      the predictors of outcome of nonoperative approaches.

PMID- 29173434
TI  - Imaging Evaluation of Degenerative Cervical Myelopathy: Current State of the Art
      and Future Directions.
AB  - Degenerative cervical myelopathy (DCM) is a common neurologic condition that is
      often treated with surgery. Imaging plays a central role in the management of
      DCM, including diagnosis, preoperative planning, postoperative assessment, and
      prognostication. Radiographs, CT, and MRI offer unique and complementary
      assessments, and all have important uses in current clinical practice. Emerging
      microstructural and functional MRI techniques have the potential to have a major
      impact, potentially transforming practice by offering earlier and more accurate
      diagnosis, monitoring for deterioration, and prediction of outcomes. In the
      future, it can be expected that imaging will play an even greater role in DCM
      management.

PMID- 29173435
TI  - Pathophysiology of Calcification and Ossification of the Ligamentum Flavum in the
      Cervical Spine.
AB  - Calcification of the ligamentum flavum (CLF) and ossification of the ligamentum
      flavum (OLF) in the cervical spine are differential diagnoses in patients with
      posterior extradural compressive lesions related to cervical degenerative
      disease. Preoperative computed tomography can facilitate the detection of
      characteristic findings and help to distinguish between CLF and OLF. Although
      these are rare entities in the cervical spine, adequately timed surgical
      decompression is required in most patients who present with radiculomyelopathy.

PMID- 29173436
TI  - Radiologic Evaluation of Ossification of the Posterior Longitudinal Ligament with
      Dural Ossification.
AB  - There are 3 basic radiological patterns of dural ossification (DO). Although
      double-layer DO is most common, when examining neuroimaging of ossification of
      the posterior longitudinal ligament (OPLL), isolated DO or masse DO should be
      kept in mind. Bone window computed tomography (CT) is most sufficient in
      identifying any type of DO associated with OPLL. Sagittal reformation of CT has
      replaced polytomography. MRI is not optimal for identification of DO and OPLL.
      Surgical approaches should be determined based on this important radiological
      information to avoid an unexpected complication. Expansive laminoplasty is the
      procedure of choice when DO is predominant.

PMID- 29173437
TI  - Ossification of the Ligaments in the Cervical Spine, Including Ossification of
      the Anterior Longitudinal Ligament, Ossification of the Posterior Longitudinal
      Ligament, and Ossification of the Ligamentum Flavum.
AB  - Ossification of the posterior longitudinal ligament (OPLL), ossification of the
      anterior longitudinal ligament (OALL), and ossification of the ligamentum flavum
      (OLF) sometimes are seen in the same patients, but the exact coexisting
      frequencies are not clear especially in the cervical region. The most frequent
      combination is OPLL and OALL. Cervical OPLL can coexist with thoracic OLF but is
      rarely associated with cervical OLF. All of these ossifying diseases of the
      cervical spinal ligaments are influenced by dynamic factors of the spinal column.
      The most frequent levels in the cervical spine affected by OPLL, OALL, and OLF
      are different because of anatomic differences inherent to each ligament.

PMID- 29173438
TI  - Importance of Sagittal Alignment of the Cervical Spine in the Management of
      Degenerative Cervical Myelopathy.
AB  - Cervical spine sagittal malalignment correlates with worse symptoms and outcomes
      in patients with degenerative cervical myelopathy (DCM), and should influence
      surgical management. An anterior versus posterior surgical approach may not
      significantly change outcomes in patients with preoperative lordosis; however,
      most studies suggest improved neurologic recovery among kyphotic patients after
      adequate correction of local sagittal alignment through an anterior or combined
      anterior-posterior approach. There are no comprehensive guidelines for DCM
      management in the setting of cervical malalignment; therefore, surgical
      management should be tailored to individual patients and decisions made at the
      discretion of treating surgeons with attention to basic principles.

PMID- 29173439
TI  - Anterior Cervical Option to Manage Degenerative Cervical Myelopathy.
AB  - Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord
      dysfunction in the world. There are multiple types of anterior approaches for
      treating patients with DCM. Many strategies have been developed to reduce
      complications for multilevel anterior surgery. Posterior approaches are sometimes
      used to supplement more extensive anterior approaches. More recently, multilevel
      cervical arthroplasty has been used for this condition. More data soon will be
      available comparing anterior and posterior approaches with the goal of optimizing
      patient-related quality of life and reducing complications, which include
      dysphagia, weakness, and instrumentation failure in some cases.

PMID- 29173440
TI  - Laminectomy with or Without Fusion to Manage Degenerative Cervical Myelopathy.
AB  - Stand-alone cervical laminectomy for degenerative cervical myelopathy (DCM) has
      become increasingly rare due to risk of postlaminectomy kyphosis. This article
      discusses the biomechanics of cervical degeneration and how laminectomy effects
      spine stability, and summarizes relevant clinical studies to help guide surgical
      decision-making for the posterior treatment of DCM. Laminectomy and fusion
      remains a safe and efficacious treatment. Stand-alone laminectomy should only be
      used for a highly selected patient population with relative stiff lordotic
      cervical spines, using care to not disrupt facets and C2 and C7 muscle
      attachments.

PMID- 29173441
TI  - Current Knowledge in Degenerative Cervical Myelopathy.

PMID- 29173442
TI  - Clinical diagnosis of idiopathic pleuroparenchymal fibroelastosis: A
      retrospective multicenter study.
AB  - BACKGROUND: Although the accurate diagnosis of pleuroparenchymal fibroelastosis
      (PPFE) requires pathologic evaluation, this diagnosis is often suggested when the
      radiologic findings are consistent with typical PPFE and when pulmonary apical
      cap, which radiologically and pathologically mimics PPFE, can be excluded by
      confirming disease progression. The aim of this study was to evaluate the
      validity of the clinical diagnosis of idiopathic PPFE. METHODS: We recruited 44
      patients with idiopathic PPFE according to our modified diagnostic criteria: 1) a
      radiologic PPFE pattern (i.e., bilateral subpleural dense consolidation with or
      without pleural thickening in the upper lobes and less marked or absent
      involvement of the lower lobes), 2) radiologic confirmation of disease
      progression, and 3) exclusion of other lung diseases with identifiable
      etiologies. The patients' baseline characteristics and clinical course were
      reviewed. RESULTS: The median age was 70 years, and 28 patients were males. The
      majority revealed emaciation, hypercapnia, and a high ratio of residual volume to
      total lung capacity. On chest computed tomography, 39 patients showed abnormal
      shadows in the lower lobes; more than half were classified as having usual
      interstitial pneumonia (UIP)/possible UIP pattern. Pneumothorax was the most
      frequent complication (33/44). The median overall survival time after diagnosis
      was 35.3 months. The presence of lower lobe UIP/possible UIP pattern did not show
      a significant prognostic impact. CONCLUSIONS: Using our diagnostic criteria, we
      could recruit relatively many patients with similar characteristics to those of
      idiopathic PPFE patients in the literature. The possibility of clinical diagnosis
      of idiopathic PPFE should be further discussed.

PMID- 29173443
TI  - Omalizumab treatment for allergic bronchopulmonary aspergillosis in young
      patients with cystic fibrosis.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a severe lung
      disease complication caused by an Aspergillus fumigatus-induced hypersensitivity
      that affects 2-15% of patients with cystic fibrosis (CF). The mainstay treatment
      consists of a combination of corticosteroids and antifungals. However, repeated
      or long-term corticosteroid therapies can lead to serious side effects. The
      monoclonal anti-IgE antibody, omalizumab, has demonstrated its efficacy in
      allergic asthma. As ABPA results from a hypersensitivity to a specific allergen,
      omalizumab might benefit CF patients with ABPA. Therefore, we conducted a
      retrospective study to investigate the effects of omalizumab on ABPA in CF
      patients. METHODS: We retrospectively analyzed the clinical records of young
      patients with CF treated with omalizumab for an ABPA in several French CF
      centers. The clinical data were collected 3 months before the start of omalizumab
      treatment, at initiation, and every 3 months up to 12 following initiation. These
      data comprised clinical, biological, nutritional, and functional parameters.
      RESULTS: Eighteen patients were included (mean age: 17.1 +/- 5.2 yrs). Under
      omalizumab was observed a stabilization of the lung function decline associated
      with a significant decrease in the corticosteroid daily dose (p = 0.0007) and an
      improvement in the nutritional status (p = 0.01). No serious side effect of
      omalizumab was reported. CONCLUSIONS: This study suggests that omalizumab might
      be an interesting therapeutic strategy in ABPA, associated with less side effects
      compared to long-term corticosteroids. Further randomized-controlled trials are
      needed to ascertain the efficacy of omalizumab in CF patients with ABPA.

PMID- 29173444
TI  - Combined effects of multiple risk factors on asthma in school-aged children.
AB  - BACKGROUND: Little is known about synergistic effects of several risk factors on
      asthma. We developed a risk score in Puerto Rican children, and then used this
      score to estimate the combined effects of multiple risk factors on asthma at
      school age in Puerto Rican and Swedish children. METHODS: Case-control study in
      609 Puerto Rican children (aged 6-14 years) and longitudinal birth cohort study
      of 2290 Swedish children followed up to age 12 years (The Children, Allergy,
      Milieu, Stockholm, Epidemiological Survey [BAMSE] Study). In both cohorts, there
      was data on parental asthma, sex, obesity, allergic rhinitis, and early-life
      second-hand smoke (SHS); data on diet and (in children >=9 years) lifetime
      exposure to gun violence were also available in the Puerto Rico study. Asthma was
      defined as physician-diagnosed asthma and >=1 episode of wheeze in the previous
      year. RESULTS: In a multivariable analysis in Puerto Rican children, male sex,
      parental asthma, allergic rhinitis, early-life SHS, an unhealthy diet and (in
      children >=9 years) gun violence were each significantly associated with asthma.
      We next created a risk score using these variables (range, 0 to 5-6 in Puerto
      Rico and 0 to 4 in BAMSE). Compared with Puerto Rican children without any risk
      factors (i.e. a score of 0), Puerto Rican children with 2, 3, and at least 4 risk
      factors had 3.6 times (95% CI = 1.4-9.2), 10.4 times (95% CI = 4.0-27.0), and
      21.6 times (95% CI = 7.2-64.9) significantly higher odds of asthma, respectively.
      In BAMSE, the presence of 2, 3, and at least 4 risk factors was significantly
      associated with 4.1 times (95% CI = 2.3-7.4), 6.3 times (95% CI = 3.0-13.3), and
      17.2 times (95% CI = 4.1-73.2) increased odds of asthma at age 12 years.
      CONCLUSIONS: Our findings emphasize the multifactorial etiology of asthma, and
      suggest that concurrent eradication or reduction of several modifiable risk
      factors may better prevent or reduce the burden of childhood asthma.

PMID- 29173445
TI  - An international comparison of asthma, wheeze, and breathing medication use among
      children.
AB  - BACKGROUND: There is variation in childhood asthma between countries with
      typically higher prevalence in "Westernized" nations. We compared asthma,
      respiratory symptoms, and medication prevalence in Eastern and Central European
      regions and Canada. METHODS: We conducted a cross-sectional survey study of
      children (5-15 years) from one urban centre in each of Canada, Belarus, Poland,
      Republic of Georgia (Adjara), Republic of Macedonia, and Ukraine. Surveys were
      distributed through randomly selected schools to parents (2013-2015). RESULTS:
      The prevalence of asthma differed by country from 20.6% in Canada to 1.5% in
      Ukraine (p < 0.001). This association remained after confounder adjustment.
      Except for Canada (58.7%) and Poland (42.5%), less than 10% of children with a
      history of wheeze had a diagnosis of asthma. Regardless of country, more than 50%
      of children with a diagnosis of asthma used breathing medications in the past
      year. Finally, except for Georgia (12.1%), all countries had a prevalence of ever
      wheeze above 20% (23.8% in Poland to 30.9% in Macedonia). CONCLUSIONS: Despite
      large differences in asthma prevalence, respiratory morbidity was more comparable
      suggesting asthma prevalence may be underestimated. Further validation of asthma
      diagnosis is needed. It is important to promote best diagnostic practices among
      first contact physicians.

PMID- 29173446
TI  - Serum folate concentrations, asthma, atopy, and asthma control in Peruvian
      children.
AB  - BACKGROUND: The relationship between folate status and asthma-related outcomes
      has not been carefully examined in low- and middle-income countries where folate
      deficiency is common. METHODS: Ancillary analysis of an unmatched case-control
      study in which we analyzed serum folate concentrations in 412 children with
      asthma and 342 controls living in peri-urban communities in Lima, Peru. We
      examined baseline associations between folate and asthma, atopy, total serum IgE,
      pulmonary function, and fractional exhaled nitric oxide. We then followed
      children with asthma longitudinally for 6-9 months and assessed associations
      between folate and odds of uncontrolled asthma (defined as Asthma Control Test
      score <= 19) and of >=1 emergency visits during follow-up. RESULTS: A 10 ng/mL
      decrease in serum folate was associated with 45% higher adjusted odds of asthma
      (OR = 1.45, 95% CI 1.05-2.02). The folate-asthma relationship differed by atopic
      status: a 10 ng/mL decrease in serum folate was associated with a 2.4-fold higher
      odds of asthma among children without atopy (2.38, 1.20-4.72) and 23% higher odds
      of asthma in children with atopy (1.23, 0.85-1.80). Among children with asthma, a
      10 ng/mL decrease in serum folate was associated with 62% higher odds of
      uncontrolled asthma (1.62, 1.02-2.56) and 73% higher odds of >=1 emergency visits
      during follow-up (1.73, 1.05-2.85). CONCLUSIONS: Serum folate concentrations were
      inversely associated with asthma, but this effect was stronger in children
      without atopy. Among children with asthma, lower serum folate concentrations were
      associated with higher risk of uncontrolled asthma.

PMID- 29173447
TI  - Clinical characteristics and treatment outcomes of pleural effusions in patients
      with nontuberculous mycobacterial disease.
AB  - BACKGROUND: The incidence of nontuberculous mycobacterial (NTM) infection has
      increased over the last 10 years. However, the clinical characteristics and
      treatment outcomes of patients with NTM pleuritis have not been well defined.
      METHODS: Patients with pleural effusion and NTM lung disease diagnosed between
      1997 and 2013 were enrolled and their medical records were reviewed
      retrospectively. The subjects were divided into definite (n = 9, NTM isolated
      from the pleura or pleural effusion) and possible (n = 5, NTM lung disease with
      pleural effusion and improvement of effusion after anti-NTM treatment) groups.
      Clinical characteristics and treatment outcomes were analyzed. Patients with
      Mycobacterium avium complex (MAC) lung disease but without pleuritis were
      selected (the MAC-LD group) and compared with the MAC pleuritis (MAC-PD) group.
      RESULTS: The median age of the 14 NTM pleuritis patients was 68 years, and the
      majority were men (9/14, 64.3%). Mycobacterium intracellulare was the most common
      species detected (50.0%), followed by M. avium (35.7%), M. abscessus (7.1%) and
      M. kansasii (7.1%). The median lymphocyte frequency and adenosine deaminase level
      in the effusion were 83% and 97 IU/L, respectively. Eight patients successfully
      completed treatment, although 2 patients died as a consequence of uncontrolled
      NTM disease. The MAC-PD group had less nodular bronchiectatic lung features and a
      lower treatment success rate than the MAC-LD group. CONCLUSION: The laboratory
      characteristics of pleural effusions from patients with NTM disease were similar
      to those of patients with tuberculous pleuritis. The treatment outcome of MAC-PD
      appears to be worse than that of MAC-LD. Therefore, clinicians need to be alert
      to successfully manage patients with MAC-PD.

PMID- 29173448
TI  - Fractional exhaled nitric oxide and multiple breath nitrogen washout in preschool
      healthy and asthmatic children.
AB  - INTRODUCTION: Objectively assessing pulmonary disease is challenging in preschool
      children with asthma. We evaluated the feasibility of measuring fractional
      exhaled nitrogen oxide (FeNO) and multiple breath nitrogen washout (N2MBW) in
      children. We compared their capacities for discriminating between children with
      asthma and healthy controls. METHODS: We measured FeNO and N2MBW-derived indices
      of lung clearance (LCI2.5) and conductive and acinar ventilation heterogeneity
      (Scond and Sacin) in 65 preschool children; 35 with physician-diagnosed asthma
      and 30 healthy. FeNO was measured with a portable device (sampling time, 6 s). We
      employed data quality control guidelines on N2MBW. Feasibility was evaluated in a
      maximum of 8 attempts for both methods. Atopic co-morbidity and first-degree
      disposition were evaluated with the ISAAC-questionnaire. RESULTS: FeNO and N2MBW
      testing were feasible in 45% and 91% of children, respectively. Feasibility was
      highly age-dependent. In children under 4 years old, FeNO was not feasible, but
      N2MBW was 85% feasible. Children with asthma had significantly elevated Scond
      values (median; 95% CI) (0.024; 0.020; 0.029) compared to healthy controls
      (0.019; 0.016; 0.023), but similar FeNO, LCI2.5 and Sacinvalues. CONCLUSION: The
      feasibility of measuring FeNO was highly age-dependent and not applicable in
      children under age 4. N2MBW was feasible in the majority of preschool children.
      Scond, but not FeNO, could discriminate between children with asthma and healthy
      controls.

PMID- 29173449
TI  - Hyponatremia in infants with new onset moderate-severe bronchiolitis: A cross
      sectional study.
AB  - BACKGROUND: The reported cumulative prevalence of hyponatremia (sodium <135
      mmol/L) in bronchiolitis is 28%. However, sodium level was never measured by
      direct potentiometry, the method recommended by the International Federation of
      Clinical Chemistry and Laboratory Medicine. Aim of this study was to assess the
      prevalence of hyponatremia, measured by direct potentiometry, in infants with
      moderate-severe bronchiolitis. METHODS: A prospective cross-sectional study was
      conducted in infants >=1month and <=24months of age with bronchiolitis. RESULTS:
      160 consecutive infants were enrolled. Hyponatremia was observed in 91 (57%)
      patients and occurred more commonly in infants <=6 months than in older infant (P
      < 0.005). CONCLUSION: The first study on sodium level measured by the direct
      potentiometry in infants with bronchiolitis points out that the prevalence of
      hyponatremia is two-fold higher than so far reported.

PMID- 29173451
TI  - Editorial.

PMID- 29173450
TI  - Outcomes of pulmonary tuberculosis in patients with discordant phenotypic
      isoniazid resistance testing.
AB  - INTRODUCTION: The discrepancy rates of drug susceptibility testing (DST) results
      between solid and liquid media have been reported to range from 2.4 to 7.4% for
      isoniazid. Most isolate with isoniazid DST discrepancies between solid and liquid
      media test as susceptible on solid medium and resistant in liquid medium,
      however, the optimal management of patients with discordant testing is unknown.
      This study was conducted to evaluate the effect of treatment regimen on treatment
      outcomes when patients with rifampicin-susceptible pulmonary tuberculosis have
      isoniazid resistance (INH-R) in liquid medium but isoniazid susceptibility (INH
      S) on solid medium. METHOD: This study was retrospectively conducted by reviewing
      patient medical records on the liquid compared to solid culture based phenotypic
      testing at Samsung Medical Center between January 2009 and December 2015. The
      study population which have INH-R in liquid medium and INH-S on solid medium was
      divided into two groups: group A (n = 30), which included patients treated for
      INH-S tuberculosis by discontinuing pyrazinamide (and ethambutol), and group B (n
      = 56), which included patients treated for INH-R tuberculosis by continuing
      pyrazinamide and/or adding fluoroquinolone. Unfavorable outcomes included
      treatment failure and relapse. RESULTS: There were no statistically significant
      differences between the two groups including demographic data, comorbidities,
      radiologic data, and treatment duration. However, baseline smear positive rates
      were more frequent in group A (19/30, 63.3%) than in group B (22/56, 39.3%; P =
      0.033). Only three patients had unfavorable outcomes; one was bacteriologically
      proven treatment failure and the other two were clinically judged as unfavorable
      outcomes. All of them were in the group A (3/30, 10%); no unfavorable outcomes
      occurred in the group B (0/56, 0%; P = 0.040). CONCLUSIONS: Unfavorable outcomes
      were less frequent in the group B than in the group A, indicating that treatment
      regimen modification according to DST results on liquid medium could improve
      treatment outcomes in patients with rifampicin-susceptible pulmonary
      tuberculosis. Further studies are required to confirm these findings to overcome
      the small number of unfavorable outcomes.

PMID- 29173452
TI  - Practical evaluation of an RNA-based saliva identification method.
AB  - Identifying saliva in samples found at crime scenes is important to clarify the
      tissue origin of DNA obtained for identification of individuals. Recently, a
      novel messenger RNA-based approach using two saliva-specific markers, Statherin
      (STATH) and Histatin 3 (HTN3), has been reported. This method can identify saliva
      more specifically than conventional amylase-based methods. Here, we performed
      several evaluations related to applying this method to real-world forensic work.
      First, we evaluated the effects of exposure to blue light (450nm) or to the
      reagent on Phadebas paper, which are direct methods used to locate saliva stains,
      on the stability of the RNA markers. The results demonstrate that exposure to the
      two direct tests did not affect the stability of the RNA markers. Second, we
      performed a comparative analysis of RNA-based and amylase-based conventional
      methods to examine the sensitivity and stability of the markers under various
      storage conditions. Although there was no difference in the sensitivity of the
      two methods for detecting 1-day-old saliva stains, a time-course study
      demonstrated that the RNA saliva markers were less stable than amylase,
      especially in wet conditions. During this time-course experiment, the stability
      of human DNA was also investigated. Although DNA was also unstable in wet
      conditions, it was more stable than the RNA markers in dry conditions. Taking the
      above results into consideration, we suggest that the RNA method could be
      introduced to current saliva identification procedures and should be used as a
      supplementary method to strongly support identification of saliva by the amylase
      based method.

PMID- 29173453
TI  - Design, optimisation and preliminary validation of a human specific loop-mediated
      amplification assay for the rapid detection of human DNA at forensic crime
      scenes.
AB  - The identification of samples at a crime scene which require forensic DNA typing
      has been the focus of recent research interest. We propose a simple, but
      sensitive analysis system which can be deployed at a crime scene to identify
      crime scene stains as human or non-human. The proposed system uses the isothermal
      amplification of DNA in a rapid assay format, which returns results in as little
      as 30min from sampling. The assay system runs on the Genie II device, a proven in
      field detection system which could be deployed at a crime scene. The results
      presented here demonstrate that the system was sufficiently specific and
      sensitive and was able to detect the presence of human blood, semen and saliva on
      mock forensic samples.

PMID- 29173454
TI  - Strengthening forensic DNA decision making through a better understanding of the
      influence of cognitive bias.
AB  - Cognitive bias may influence process flows and decision making steps in forensic
      DNA analyses and interpretation. Currently, seven sources of bias have been
      identified that may affect forensic decision making with roots in human nature;
      environment, culture, and experience; and case specific information. Most of the
      literature and research on cognitive bias in forensic science has focused on
      patterned evidence; however, forensic DNA testing is not immune to bias,
      especially when subjective interpretation is involved. DNA testing can be
      strengthened by recognizing the existence of bias, evaluating where it influences
      decision making, and, when applicable, implementing practices to reduce or
      control its effects. Elements that may improve forensic decision making regarding
      bias include cognitively informed education and training, quality assurance
      procedures, review processes, analysis and interpretation, and context management
      of irrelevant information. Although bias exists, reliable results often can be
      (and have been) produced. However, at times bias can (and has) impacted the
      interpretation of DNA results negatively. Therefore, being aware of the dangers
      of bias and implementing measures to control its potential impact should be
      considered. Measures and procedures that handicap the workings of the crime
      laboratory or add little value to improving the operation are not advocated, but
      simple yet effective measures are suggested. This article is meant to raise
      awareness of cognitive bias contamination in forensic DNA testing and to give
      laboratories possible pathways to make sound decisions to address its influences.

PMID- 29173455
TI  - Rapid identification information and its influence on the perceived clues at a
      crime scene: An experimental study.
AB  - Crime scenes can always be explained in multiple ways. Traces alone do not
      provide enough information to infer a whole series of events that has taken
      place; they only provide clues for these inferences. CSIs need additional
      information to be able to interpret observed traces. In the near future, a new
      source of information that could help to interpret a crime scene and testing
      hypotheses will become available with the advent of rapid identification
      techniques. A previous study with CSIs demonstrated that this information had an
      influence on the interpretation of the crime scene, yet it is still unknown what
      exact information was used for this interpretation and for the construction of
      their scenario. The present study builds on this study and gains more insight
      into (1) the exact investigative and forensic information that was used by CSIs
      to construct their scenario, (2) the inferences drawn from this information, and
      (3) the kind of evidence that was selected at the crime scene to (dis)prove this
      scenario. We asked 48 CSIs to investigate a potential murder crime scene on the
      computer and explicate what information they used to construct a scenario and to
      select traces for analysis. The results show that the introduction of rapid ID
      information at the start of an investigation contributes to the recognition of
      different clues at the crime scene, but also to different interpretations of
      identical information, depending on the kind of information available and the
      scenario one has in mind. Furthermore, not all relevant traces were recognized,
      showing that important information can be missed during the investigation. In
      this study, accurate crime scenarios where mainly build with forensic
      information, but we should be aware of the fact that crime scenes are always
      contaminated with unrelated traces and thus be cautious of the power of rapid ID
      at the crime scene.

PMID- 29173456
TI  - Recognition of computerized facial approximations by familiar assessors.
AB  - Studies testing the effectiveness of facial approximations typically involve
      groups of participants who are unfamiliar with the approximated individual(s).
      This limitation requires the use of photograph arrays including a picture of the
      subject for comparison to the facial approximation. While this practice is often
      necessary due to the difficulty in obtaining a group of assessors who are
      familiar with the approximated subject, it may not accurately simulate the
      thought process of the target audience (friends and family members) in comparing
      a mental image of the approximated subject to the facial approximation. As part
      of a larger process to evaluate the effectiveness and best implementation of the
      ReFace facial approximation software program, the rare opportunity arose to
      conduct a recognition study using assessors who were personally acquainted with
      the subjects of the approximations. ReFace facial approximations were generated
      based on preexisting medical scans, and co-workers of the scan donors were tested
      on whether they could accurately pick out the approximation of their colleague
      from arrays of facial approximations. Results from the study demonstrated an
      overall poor recognition performance (i.e., where a single choice within a pool
      is not enforced) for individuals who were familiar with the approximated
      subjects. Out of 220 recognition tests only 10.5% resulted in the assessor
      selecting the correct approximation (or correctly choosing not to make a
      selection when the array consisted only of foils), an outcome that was not
      significantly different from the 9% random chance rate. When allowed to select
      multiple approximations the assessors felt resembled the target individual, the
      overall sensitivity for ReFace approximations was 16.0% and the overall
      specificity was 81.8%. These results differ markedly from the results of a
      previous study using assessors who were unfamiliar with the approximated
      subjects. Some possible explanations for this disparity in performance were
      examined, and it was ultimately concluded that ReFace facial approximations may
      have limited effectiveness if used in the traditional way. However, some
      promising alternative uses are explored that may expand the utility of facial
      approximations for aiding in the identification of unknown human remains.

PMID- 29173457
TI  - Blast injury prevalence in skeletal remains: Are there differences between
      Bosnian war samples and documented combat-related deaths?
AB  - Court cases at the International Criminal Tribunal for the Former Yugoslavia
      (ICTY) have seen questions raised about the recognition and causes of blast
      related trauma and the relationship to human rights abuses or combat. During
      trials, defence teams argued that trauma was combat related and prosecutors
      argued that trauma was related to executions. We compared a sample of 81 cases
      (males between 18 and 75) from a Bosnian mass grave investigation linked to the
      Kravica warehouse killings to published combat-related blast injury data from
      World War One, Vietnam, Northern Ireland, the first Gulf War, Operation Iraqi
      Freedom and Afghanistan. We also compared blast fracture injuries from Bosnia to
      blast fracture injuries sustained in bombings of buildings in two non-combat
      'civilian' examples; the Oklahoma City and Birmingham pub bombings. A Chi-squared
      statistic with a Holm-Bonferroni correction assessed differences between
      prevalence of blast-related fractures in various body regions, where data were
      comparable. We found statistically significant differences between the Bosnian
      and combat contexts. We noted differences in the prevalence of head, torso,
      vertebral area, and limbs trauma, with a general trend for higher levels of more
      widespread trauma in the Bosnian sample. We noted that the pattern of trauma in
      the Bosnian cases resembled the pattern from the bombing in buildings civilian
      contexts. Variation in trauma patterns can be attributed to the influence of
      protective armour; the context of the environment; and the type of munition and
      its injuring mechanism. Blast fracture injuries sustained in the Bosnian sample
      showed patterns consistent with a lack of body armour, blast effects on people
      standing in enclosed buildings and the use of explosive munitions.

PMID- 29173458
TI  - Can we continue to effectively police digital crime?
AB  - Now approximately 30years old, the field of digital forensics is arguably facing
      some of its greatest challenges to date. Whilst currently supporting law
      enforcement in numerous criminal cases annually, questions are beginning to
      emerge regarding whether it can sustain this contribution, with digital crime
      remaining prevalent. In his first live interview in September 2015, Head of MI5,
      Andrew Parker indicated that individuals are now engaging in computing acts which
      are beyond the control of authorities, confirming earlier remarks made by British
      Prime Minister David Cameron in the wake of the Charlie Hebdo attacks. Such
      comments cast doubt on the future effectiveness of the digital forensic
      discipline and its ability to effectively investigate those who implement the
      latest forms of technology to carry out illicit acts. This article debates the
      controversial question, could we be facing an era where digital crime can no
      longer be effectively policed?

PMID- 29173459
TI  - Conceptualising forensic science and forensic reconstruction. Part I: A
      conceptual model.
AB  - There has been a call for forensic science to actively return to the approach of
      scientific endeavour. The importance of incorporating an awareness of the
      requirements of the law in its broadest sense, and embedding research into both
      practice and policy within forensic science, is arguably critical to achieving
      such an endeavour. This paper presents a conceptual model (FoRTE) that outlines
      the holistic nature of trace evidence in the 'endeavour' of forensic
      reconstruction. This model offers insights into the different components
      intrinsic to transparent, reproducible and robust reconstructions in forensic
      science. The importance of situating evidence within the whole forensic science
      process (from crime scene to court), of developing evidence bases to underpin
      each stage, of frameworks that offer insights to the interaction of different
      lines of evidence, and the role of expertise in decision making are presented and
      their interactions identified. It is argued that such a conceptual model has
      value in identifying the future steps for harnessing the value of trace evidence
      in forensic reconstruction. It also highlights that there is a need to develop a
      nuanced approach to reconstructions that incorporates both empirical evidence
      bases and expertise. A conceptual understanding has the potential to ensure that
      the endeavour of forensic reconstruction has its roots in 'problem-solving'
      science, and can offer transparency and clarity in the conclusions and inferences
      drawn from trace evidence, thereby enabling the value of trace evidence to be
      realised in investigations and the courts.

PMID- 29173460
TI  - Conceptualising forensic science and forensic reconstruction. Part II: The
      critical interaction between research, policy/law and practice.
AB  - This paper builds on the FoRTE conceptual model presented in part I to address
      the forms of knowledge that are integral to the four components of the model.
      Articulating the different forms of knowledge within effective forensic
      reconstructions is valuable. It enables a nuanced approach to the development and
      use of evidence bases to underpin decision-making at every stage of a forensic
      reconstruction by enabling transparency in the reporting of inferences. It also
      enables appropriate methods to be developed to ensure quality and validity. It is
      recognised that the domains of practice, research, and policy/law intersect to
      form the nexus where forensic science is situated. Each domain has a distinctive
      infrastructure that influences the production and application of different forms
      of knowledge in forensic science. The channels that can enable the interaction
      between these domains, enhance the impact of research in theory and practice,
      increase access to research findings, and support quality are presented. The
      particular strengths within the different domains to deliver problem solving
      forensic reconstructions are thereby identified and articulated. It is argued
      that a conceptual understanding of forensic reconstruction that draws on the full
      range of both explicit and tacit forms of knowledge, and incorporates the
      strengths of the different domains pertinent to forensic science, offers a
      pathway to harness the full value of trace evidence for context sensitive,
      problem-solving forensic applications.

PMID- 29173461
TI  - Response paper to "The likelihood of encapsulating all uncertainty": The
      relevance of additional information for the LR.
AB  - In this response paper, part of the Virtual Special Issue on "Measuring and
      Reporting the Precision of Forensic Likelihood Ratios", we further develop our
      position on likelihood ratios which we described previously in Berger et al.
      (2016) "The LR does not exist". Our exposition is inspired by an example given in
      Martire et al. (2016) "On the likelihood of encapsulating all uncertainty", where
      the consequences of obtaining additional information on the LR were discussed. In
      their example, two experts use the same data in a different way, and the LRs of
      these experts change differently when new data are taken into account. Using this
      example as a starting point we will demonstrate that the probability distribution
      for the frequency of the characteristic observed in trace and reference material
      can be used to predict how much an LR will change when new data become available.
      This distribution can thus be useful for such a sensitivity analysis, and address
      the question of whether to obtain additional data or not. But it does not change
      the answer to the original question of how to update one's prior odds based on
      the evidence, and it does not represent an uncertainty on the likelihood ratio
      based on the current data.

PMID- 29173462
TI  - What should a forensic practitioner's likelihood ratio be? II.
AB  - In the debate as to whether forensic practitioners should assess and report the
      precision of the strength of evidence statements that they report to the courts,
      I remain unconvinced by proponents of the position that only a subjectivist
      concept of probability is legitimate. I consider this position counterproductive
      for the goal of having forensic practitioners implement, and courts not only
      accept but demand, logically correct and scientifically valid evaluation of
      forensic evidence. In considering what would be the best approach for evaluating
      strength of evidence, I suggest that the desiderata be (1) to maximise
      empirically demonstrable performance; (2) to maximise objectivity in the sense of
      maximising transparency and replicability, and minimising the potential for
      cognitive bias; and (3) to constrain and make overt the forensic practitioner's
      subjective-judgement based decisions so that the appropriateness of those
      decisions can be debated before the judge in an admissibility hearing and/or
      before the trier of fact at trial. All approaches require the forensic
      practitioner to use subjective judgement, but constraining subjective judgement
      to decisions relating to selection of hypotheses, properties to measure, training
      and test data to use, and statistical modelling procedures to use - decisions
      which are remote from the output stage of the analysis - will substantially
      reduce the potential for cognitive bias. Adopting procedures based on relevant
      data, quantitative measurements, and statistical models, and directly reporting
      the output of the statistical models will also maximise transparency and
      replicability. A procedure which calculates a Bayes factor on the basis of
      relevant sample data and reference priors is no less objective than a frequentist
      calculation of a likelihood ratio on the same data. In general, a Bayes factor
      calculated using uninformative or reference priors will be closer to a value of 1
      than a frequentist best estimate likelihood ratio. The bound closest to 1 based
      on a frequentist best estimate likelihood ratio and an assessment of its
      precision will also, by definition, be closer to a value of 1 than the
      frequentist best estimate likelihood ratio. From a practical perspective, both
      procedures shrink the strength of evidence value towards the neutral value of 1.
      A single-value Bayes factor or likelihood ratio may be easier for the courts to
      handle than a distribution. I therefore propose as a potential practical
      solution, the use of procedures which account for imprecision by shrinking the
      calculated Bayes factor or likelihood ratio towards 1, the choice of the
      particular procedure being based on empirical demonstration of performance.

PMID- 29173463
TI  - The meaning of justified subjectivism and its role in the reconciliation of
      recent disagreements over forensic probabilism.
AB  - In this paper we reply to recent comments in this Special Issue according to
      which subjective probability is not considered to be a concept fit for use in
      forensic evaluation and expert reporting. We identify the source of these
      criticisms to lie in a misunderstanding of subjective probability as
      unconstrained subjective probability; a lack of constraint that neither
      corresponds to the way in which we referred to subjective probability in our
      previous contributions, nor to the way in which probability assignment is
      understood by current evaluative guidelines (e.g., of ENFSI). Specifically, we
      explain that we understand subjective probability as a justified assertion, i.e.
      a conditional assessment based on task-relevant data and information, that may be
      thought of as a constrained subjective probability. This leads us to emphasise
      again the general conclusion that there is no gap between justified (or,
      reasonable) subjective probability and other concepts of probability in terms of
      its ability to provide assessments that are soundly based on whatever relevant
      information available. We also note that the challenges an expert faces in
      reporting probabilities apply equally to all interpretations of probability, not
      only to subjective probability.

PMID- 29173464
TI  - Manganese modulates the physiological and biochemical responses of Mentha
      aquatica L. to ultraviolet radiation.
AB  - Ultraviolet (UV) radiation as an environmental factor alters the physiological
      and metabolic processes in plants. Manganese (Mn) is an essential element that is
      required for plant growth and development. This experiment was conducted in order
      to determine the effects of Mn supply and UV radiation on the physiological and
      metabolic responses in Mentha aquatica. With this aim, three levels of Mn and UV
      treatments were used as follows: basic Hoagland's nutrient solution without UV
      radiation (control), Mn supply (100MUM), UV radiation (2h daily), and UV+100MUM
      Mn. After three weeks of treatments, the root and shoot dry weights and the
      contents of photosynthetic pigments were decreased under UV radiation condition.
      However, the contents of flavonoids, soluble carbohydrate, anthocyanins,
      malonaldehyde (MDA), hydrogen peroxide (H2O2), and the activity of antioxidant
      enzymes (superoxide dismutase, catalase, and peroxidase) were increased.
      Interestingly, Mn at 100MUM concentration decreased the harmful effects of UV
      radiation on M. aquatica. In addition, the clear differences were observed in the
      terpene constituents of M. aquatica after the Mn and UV treatments. In this
      study, 1, 8-cineole, menthofuran and beta-caryophyllene were the most abundant
      constituents of essential oils in both the control and treated plants. The
      correlation analysis between pairs of the primary and secondary metabolites
      showed that there were positive and negative correlations among the variables
      under the Mn supply and UV radiation conditions. These findings clearly display a
      positive effect of external Mn up to 100MUM in the nutrient solution on the
      resistant of M. aquatica to UV radiation.

PMID- 29173465
TI  - The chemical speciation, spatial distribution and toxicity of mercury from
      Tibetan medicine Zuotai,beta-HgS and HgCl2 in mouse kidney.
AB  - Zuotai, a famous Tibetan medicinal mixture containing beta-HgS, has been used to
      combine with herbal remedies for treating diseases for more than 1 300 years. The
      target organ for inorganic mercury toxicity is generally considered to be the
      kidney. Therefore, it is crucial to reveal the chemical speciation, spatial
      distribution and potential nephrotoxicity of mercury from Zuotai in kidney. To
      date, this remains poorly understood. We used X-ray absorption spectroscopy (XAS)
      and micro X-ray fluorescence (MU-XRF) imaging based on synchrotron radiation to
      study mercury chemical forms and mercury special distribution in kidney after
      mice were treated orally with Zuotai, beta-HgS or HgCl2. Meanwhile, the
      histopathology of kidney was observed. Mice exposed with Zuotai showed kidney
      with significant proportion of mercury ions bound to sulfydryl biomolecules (e.g.
      Cys-S-Hg-S-Cys) plus some of unknown species, but without methylmercury cysteine,
      which is the same as beta-HgS and HgCl2. The mercury is mainly deposited in renal
      cortex in mouse treated with Zuotai, beta-HgS or HgCl2, but with a low level of
      mercury in medulla. The total mercury in kidney of mice treated with HgCl2 was
      much higher than that of beta-HgS, and the later was higher than that of Zuotai.
      And, HgCl2 cause severe impairments in mouse kidney, but that was not observed in
      the Zuotai and beta-HgS groups. Meanwhile, the bio-metals (Ca, Zn, Fe and Cu)
      micro-distributions in kidney were also revealed. These findings elucidated the
      chemical nature, spatial distribution and toxicity difference of mercury from
      Zuotai, beta-HgS and HgCl2 in mouse kidney, and provide new insights into the
      appropriate methods for biological monitoring.

PMID- 29173466
TI  - Nutritional management can assist a significant role in alleviation of
      arsenicosis.
AB  - Consumption of arsenic contaminated water causes serious skin disease and cancer
      in a significant number of exposed people. Chelating agents, consider an
      expensive therapy, are employed in the treatment of arsenic intoxication. There
      are reports which suggest that the poorest suffer the most from arsenicosis. This
      may be due to improper diet intake, consist of low protein and micronutrients
      which increase the vulnerability to arsenic-related disorders. Several human
      studies demonstrated the associations between malnourishment and the development
      of arsenic-caused skin lesions, skin cancer and cardiovascular effects. Thus,
      there is an urgent need of implementation of mitigation strategies for improving
      the health of exposed populations. Nutrition enhances the detoxification process
      so food rich in vitamins, protein, antioxidants help in its detoxification
      process. Methylation is the detoxification process which takes place via S
      adenosylmethionine (SAM). It is a methyl group donor and it derived its methyl
      group from diet. Nutritional intervention thus may appear as a practical and
      inexpensive approach. Nutrition provides protection from toxic effect of arsenic
      by two ways (i) methylation of As (ii) antioxidants which provides protection
      against free radical species. The governments and NGOs may run awareness
      programmes in arsenic affected area regarding prevention and alternate therapy
      which can decrease the susceptibility of the exposed population. They could also
      help in distributing cheaper, high protein diets particularly to the masses who
      cannot afford such foods. Thus, to prevent arsenicosis alternate therapy and
      proper nutrition could be the important strategy for alleviating its toxic
      effects. This mini review provides an insight on the importance of nutrition in
      preventing adverse effect cause by arsenic to suffer population.

PMID- 29173467
TI  - Augmentation of antioxidant and iron(III) chelation properties of tertiary
      mixture of bioactive ligands.
AB  - The excess of iron in plasma and cellular compartment pose direct and indirect
      toxic effects. In the present investigation, we proposed additive function of
      nutritional bioactive ligands in combination which has shown enhanced antioxidant
      and iron(III) chelation property. The optimal interaction and in vitro
      antioxidant activity of tertiary mixture comprising of curcumin+quercetin+gallic
      acid was validated by central composite design (CCD) based on ferric reducing
      antioxidant power assay (FRAP). The additive denticity of nutritional bioactive
      ligands was investigated by UV-vis, FTIR & MALDI-TOF-MS analysis, which has given
      substantial evidence for the formation of tris-bidentate [curcumin-quercetin
      gallic acid-Fe(III)] co-ordination complex. The in vivo proof of concept of the
      hypothesis was tested in iron intoxicated male wistar rats intoxicated with iron
      dextran. Co-administration curcumin+quercetin+gallic acid (CQG) exhibit dose
      dependent response & found effective in subsiding acute iron intoxication both at
      plasma and cellular level, evaluated by studies including serum ferritin, ICP
      OES, lipid peroxidation and histopathology studies among others. Thus, we
      conclude that in vitro and in vivo studies supported our hypothesis to deduce
      additive function nutritional ligands to counteract direct and indirect effects
      of iron(III).

PMID- 29173468
TI  - Spatially resolved quantification of gadolinium deposited in the brain of a
      patient treated with gadolinium-based contrast agents.
AB  - Due to its paramagnetic properties resulting from seven unpaired f-electrons, Gd
      is frequently applied in magnetic resonance imaging examinations. Due to the
      acute toxicity of free Gd3+, ligand ions based on polyaminocarboxylic acids are
      used to create thermodynamically stable linear or macrocyclic complexes. The
      highly water soluble Gd-based contrast agents (GBCAs) are known to be excreted
      fast and unmetabolized, mostly via the kidneys. Nevertheless, recent studies
      showed that Gd traces persists not only in animal but also in human brain. Aim of
      this study was the development and application of an analytical method for the
      spatially resolved quantification of gadolinium traces in human brain thin
      sections of a patient treated with GBCAs. For this retrospective study different
      human brain regions were selected to analyze the distribution of gadolinium. An
      additional patient served as control sample, as no GBCA was administered. Deep
      frozen brain thin sections were analyzed by laser ablation-inductively coupled
      plasma-mass spectrometry (LA-ICP-MS) and matrix-matched gelatin standards were
      prepared to quantify the gadolinium deposits via an external calibration. LA-ICP
      MS analyses with high spatial resolution showed gadolinium deposits in different
      brain regions with highest concentrations above 800ngg-1 more than two years
      after the last application of a GBCA. An excellent limit of quantification of
      7ngg-1, which is far below the limits of detection of MRI methods, could be
      achieved. The found concentrations confirm recent reports on gadolinium
      depositions in human brain, which were obtained without high spatial resolution.
      LA-ICP-MS provides limits of quantification, which are well suited to detect
      ultratrace amounts of gadolinium in human brain. Therefore, it provides valuable
      information on the distribution of gadolinium traces in the human brain even
      after single administration of GBCAs.

PMID- 29173469
TI  - The possible protective effects of vitamin E and selenium administration in
      oxidative stress caused by high doses of glucocorticoid administration in the
      brain of rats.
AB  - Acute exposure to high doses of glucocorticoids (GCs) may potentially increase
      the basal levels of reactive oxygen species (ROS) by altering the defence
      capacity against oxidative damage. Also, antioxidants may affect the oxidative
      breakdown of tissues. Therefore, the aim of this work was to determine the
      effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation (LPO)
      as thiobarbituric acid reactive substances (TBARS) and on the antioxidative
      defence mechanisms in the brain of rats treated with high doses of prednisolone.
      Two hundred and fifty adult male Wistar rats were randomly divided into five
      groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily
      supplement in their drinking water of 20mg vitamin E, 0.3mg Se, and a combination
      of vitamin E and Se, respectively, for 30days. For 3days subsequently, the
      control (group 1) was treated with a placebo, and the remaining 4 groups were
      injected intramuscularly with 100mg/kg body weight (bw) prednisolone. After the
      last administration of prednisolone, 10 rats from each group were killed at 4, 8,
      12, 24, and 48h and the activities of enzymes selenium-glutathione peroxidase (Se
      GSH-Px) and catalase (CAT), and the levels of reduced glutathione (reduced GSH)
      and TBARS in their brains were measured. Se-GSH-Px and CAT enzyme activities, and
      reduced GSH levels in the prednisolone treatment group (group 2) began to
      decrease gradually at 4h (p<0.01, p<0.05, respectively), falling respectively to
      60, 50, and 40% of the control levels by 24h (p<0.001, p<0.01), and recovering to
      the control levels at 48h. In contrast, prednisolone administration caused an
      increase in the brain TBARS, reaching up to six times the level of the control at
      24h (p<0.001). However, supplementation with vitamin E and Se had a preventive
      effect on the elevation of the brain TBARS and improved the diminished activities
      of antioxidative enzymes and the levels of reduced GSH. Therefore, the present
      study attempts to determine the sequence of cellular membrane damage in the brain
      of the rats after high doses GC administration and the possible roles in vivo of
      vitamin E and Se, and their combination.

PMID- 29173470
TI  - Effect of long-term aerobic, anaerobic and aerobic-anaerobic physical training in
      seric toxic minerals concentrations.
AB  - BACKGROUND: Many substances poured out from industries can be toxic to humans and
      can impair physical performance. Besides, physical training may modify the body
      concentrations of these substances as a result of physiological adaptations.
      OBJECTIVES: The aim of the study was to determine if different modalities of
      exercise might affect serum concentrations of toxic trace elements in sportsmen.
      METHODS: 80 Spanish national sportsmen were recruited before the start of their
      training period. All the athletes had been training regularly for the previous
      two years with a rigorous training target at high-level competition. 31 sedentary
      participants from the same geographic area formed the control group. Serum
      arsenic, beryllium, cadmium, cesium and lead samples were analyzed with an ICP
      MS. RESULTS: Serum concentrations were higher among the sportsmen group than
      among the control group, being highly significant in cases of Be from 0.043+/
      0.019 to 0.074+/-0.029MUg/L, Cs from 0.693+/-0.305 to 1.358+/-0.569MUg/L and Pb
      from 0.162+/-0.171 to 2.375+/-1.699MUg/L; and significant in the case of Cd from
      0.046+/-0.027 to 0.067+/-0.059MUg/L. However, if they were separated according to
      different sport modalities, it was found that, although they had higher
      concentrations than controls, there were elements that changed their
      concentrations in relation to the metabolic type of activity performed.
      CONCLUSIONS: In some cases physical exercise induces favorable adaptations to
      avoid environmental pollution damage. Endurance training (65-75% VO2max) can be
      considered the most effective exercise to prevent toxicity effects. However,
      integral-matrixes analysis are required in further research to overcome some
      controversial behaviors of some elements.

PMID- 29173471
TI  - The combined effect of supplementary Cr(III) propionate complex and iron
      deficiency on the chromium and iron status in female rats.
AB  - The aim of the study was to evaluate the combined effect of supplementary
      chromium(III) and iron deficiency on the chromium and iron status in female rats.
      The study was carried out on female Wistar rats, which were divided into 6
      experimental groups with different Fe levels (deficient 10% RDA and recommended
      (adequate) 100% RDA). Simultaneously, for six weeks their diets were supplemented
      with Cr(III) at doses of 1, 50 and 500mgkg-1. The tissular chromium and iron
      levels were measured with the AAS method. The serum iron and TIBC were measured
      with colorimetric methods The serum ferritin level was measured by means of
      electrochemiluminescence immunoassay. The serum transferrin level was measured
      with the ELISA method. The haematology was measured with an automated blood
      analyser. Supplementary Cr3 increased the Cr content in the tissues. This effect
      was weaker in the Fe-deficient groups than in those with the recommended Fe
      level, but it did not affect the Fe status. Fe deficiency significantly reduced
      the Fe content in the tissues. Simultaneously, Cr3 supplementation mitigated the
      symptoms of Fe deficiency. Fe deficiency increased TIBC and transferrin levels
      but reduced ferritin and most haematological parameters. However, simultaneous
      addition of high doses of Cr3 did not deepen these adverse changes. Our results
      show that the trend of changes in the Fe-Cr interaction depends on the content of
      these elements in the body.

PMID- 29173472
TI  - Levels of aqueous humor trace elements in patients with open-angle glaucoma.
AB  - PURPOSE: Trace elements might play a role in the complex multifactorial
      pathogenesis of open-angle glaucoma. The aim of this study was to analyze
      concentrations of trace elements in aqueous humor samples of patients with
      primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG).
      PATIENTS AND METHODS: Thirty-three aqueous humor samples were obtained from
      patients undergoing cataract surgery: 12 patients with POAG (age 65.3+/-10.50,
      female 8, male 4), 10 patients with PEXG (age 65.9+/-11.27, female 6, male 4) and
      11 patients without glaucoma (age 69.5+/-13.70, female 7, male 4) serving as
      controls. Aqueous humor levels of cadmium, iron, manganese, cobalt, copper and
      zinc were measured by Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry
      (FI-ICP-MS). RESULTS: From the statistical evaluation, we observed that patients
      with POAG had significantly higher aqueous humor levels of zinc (p=0.006)
      compared to controls. Increased aqueous humor levels of zinc were also observed
      in patients with PEXG in relation to control (p=0.0006). For iron we observed a
      significantly reduction in PEXG compared to control (p=0.002) and a significant
      difference between POAG and PEXG (p=0.0091). No significant differences were
      observed in aqueous humor levels of manganese, cobalt, copper, cadmium between
      glaucoma and control patients. No differences were seen for iron (POAG vs.
      controls). Analysis of trace element ratios was added. CONCLUSION: Significant
      differences in aqueous humor levels of zinc and iron between glaucoma and control
      patients support the hypothesis that these trace elements are involved in the
      pathogenesis of open-angle glaucoma.

PMID- 29173473
TI  - The importance of boron in biological systems.
AB  - Boron is an essential element for plants and probably essential for human and
      animal health. Boron has a broad range of physiological effects on biological
      systems at low concentrations, whereas it is toxic to at high concentrations.
      Eventhough there are many studies on boron's biological effects and toxicity,
      more information is needed to understand the mechanisms of its action. The aim of
      the current work is to review boron's function, transport and toxicity in
      different biological systems.

PMID- 29173474
TI  - Metallothionein 2A gene polymorphism and trace elements in mother-newborn pairs
      in the Croatian population.
AB  - The main source of exposure for all essential and toxic elements in the general
      population is diet. In smokers, the main route for cadmium (Cd) and lead (Pb)
      intake is the inhalation of tobacco smoke. Besides gender, age, nutrition,
      lifestyle, and physiological conditions such as pregnancy, specific genetic
      characteristics also influence individual element uptake. Metallothionein MT2 is
      a cysteine-rich low-weight protein found ubiquitously throughout the body.
      Specific gene polymorphism may influence MT2 expression and subsequent binding,
      transfer and organ accumulation of metals, though data on these influences are
      lacking, especially in human mother-newborn pairs. The objective of this study
      was to determine selected toxic (Cd, Pb, Hg) and essential (Fe, Zn, Cu, Se)
      elements in maternal blood, placenta, and cord blood (by ICP-MS), and MT2 levels
      in maternal serum (by ELISA) in relation to maternal MT2A -5A/G (rs28366003)
      polymorphism (by RFLP-PCR and electrophoresis). Study participants were healthy
      postpartum women in Croatia (n=268, mean age 29 years) with term vaginal
      childbirth in a maternity ward assigned into two study groups by self-reporting
      about their smoking habit (by questionnaire). Smokers vs. non-smokers had
      increased levels of Cd and Pb in all measured samples, Fe and Cu in cord blood,
      Zn in placenta, and MT2 in maternal serum. Among subjects with AG/GG genotype,
      placental Fe was significantly lower only among non-smokers, while MT2 levels in
      serum were lower, though not significantly, regardless of maternal smoking habit.
      There was no impact of MT2A -5A/G SNP on any element in maternal or cord blood.
      In conclusion, the results confirmed maternal smoking-related increases in Cd and
      Pb levels in the maternal-placental-foetal unit. They also provided additional
      data on concomitant metal concentrations in representative samples of maternal
      blood, placenta, and cord blood, as well as increased cord blood Fe and Cu,
      placental Zn, and maternal serum MT2 in smokers. New evidence is that MT2A -5A/G
      SNP was associated with decreased placental Fe levels in non-smokers. For a final
      conclusion on the influence of the MT2A -5A/G polymorphism on toxic and essential
      element levels in mother-newborn pairs, further research would require a larger
      number of participants divided across subgroups defined by the main source of
      particular toxic metal exposure (such as specific food intake, cigarette smoking,
      air pollution and/or occupational exposure).

PMID- 29173475
TI  - Mechanism of insulin-like effect of chromium(III) ions on glucose uptake in C2C12
      mouse myotubes involves ROS formation.
AB  - Chromium is considered a trace element which improves glucose tolerance, but
      mechanism accounting for this insulin-like action is not recognized. The main
      purpose of this study was to examine the role of reactive oxygen species (ROS) in
      chromium and insulin stimulated glucose transport using antioxidants. Effect of
      chromium ions on phosphatases, enzymes involved in inhibition of insulin
      signaling was also investigated. Experiments were performed in vitro on C2C12
      mouse myotubes. ROS level was measured with the use of confocal microscope and
      2',7' dichlorodihydrofluorescein diacetate (DCFH-DA). Glucose metabolism was
      assayed by the measurement of 2-[3H]-deoxyglucose uptake. Cr3+ ions and insulin
      treatment caused significant increase of ROS formation and also stimulated
      glucose uptake in C2C12 cells in concentration dependent manner. Antioxidants (L
      ascorbic acid and N-acetyl cysteine 100MUM) and DPI (diphenyleneiodonium-NADPH
      oxidase inhibitor, 10MUM) abolished insulin- and Cr-inducted glucose transport.
      Our results confirm the hypothesis that the ROS are integral part of insulin
      signaling pathway and that the insulin mimetic effect of Cr3+ ions depends on the
      antioxidant status of the cells. Surprisingly, chromium treatment resulted in
      increased activity of membrane phosphatases.

PMID- 29173476
TI  - Free copper in serum: An analytical challenge and its possible applications.
AB  - Copper (Cu), as an essential metal, plays a crucial role in biochemical reactions
      and in physiological regulations. Cu in plasma is mostly bound to proteins; about
      65-90% of Cu is tightly binds with caeruloplasmin and the rest of Cu is loosely
      binds with albumin and transcuprein. A small but significant relatively "free"
      fraction, probably complexed with amino acids, is present at around 5% of the
      total concentration. We developed and validated a new method for direct
      measurement of free Cu in serum by ultrafiltration with AMICON(r)Ultra 100K
      device and determination with AAS. Also, we checked that there is no trace of
      albumin in the ultrafiltrates and we demonstrated the ultrafiltration of a known
      concentration of Cu added in artificial serum without albumin and, on the
      contrary, the retention of the Cu in artificial serum with albumin. The
      ultrafiltration procedure and the instrumental determination showed a good
      repeatability and a very low limit of detection (1MUg/L). The method was applied
      to 30 healthy subjects, the mean value of the total Cu (994.8MUg/L) is included
      in the normal range for healthy people and the values of free Cu (23.6MUg/L)
      corresponding to 2.37% of the Cu total. The determination of free Cu by this
      simple and cheap method may be useful to measure the most bioavailable Cu
      fraction possibly implicated in neuro-degenerative and oxidative-stress related
      diseases.

PMID- 29173477
TI  - Copper dyshomeostasis in Wilson disease and Alzheimer's disease as shown by serum
      and urine copper indicators.
AB  - Abnormal handling of copper is the cause of Wilson disease (WD), a rare disorder
      typified by increased levels in plasma copper not-bound to ceruloplasmin (nCp-Cu,
      also known as 'free' copper). In Alzheimer's disease (AD), meta-analyses show
      that copper decreases in brain but increases in serum, due to the nCp Cu
      component increase. Despite the similarities, a direct comparison of copper
      biological status in the two diseases has never been carried out. To fill this
      gap, we evaluated serum copper, ceruloplasmin, nCp-Cu and Cu:Cp in 385 CE and 336
      healthy controls previously investigated that were compared with 9 newly
      diagnosed WD patients. We then assessed 24h copper urinary excretion in 24 WD
      patients under D-penicillamine (D-pen) treatment and in 35 healthy controls, and
      compared results with those of AD patients participating to a D-pen phase II
      clinical trial previously published. After adjusting for sex and age, serum nCp
      Cu and Cu:Cp resulted higher in AD and in WD than in healthy controls (both
      p<0.001). While nCp-Cu was similar between AD and WD, Cu:Cp was higher in WD
      (p<0.016). 24h urinary copper excretion in AD patients (12.05MUg/day) was higher
      than in healthy controls (4.82MUg/day; p<0.001). 77.8% of the AD patients under D
      pen treatment had a 24h urinary excretion higher than 200MUg/day, suggestive of a
      failure of copper control. This study provides new insight into the
      pathophysiology of copper homeostasis in AD, showing a failure of copper control
      and the Cu:Cp ratio as an eligible marker.

PMID- 29173478
TI  - Staphylococcal infections in atopic dermatitis and nickel allergy: Immunologic
      implications and elemental opportunities.

PMID- 29173479
TI  - Trace elements in struvite equine enteroliths: Concentration, speciation and
      influence of diet.
AB  - Equine enteroliths ~1.5cm in diameter were collected from an Arabian horse in
      Louisville, Kentucky, United States. Scanning electron microscopy (SEM) and light
      microscope imaging of a sectioned enterolith showed two distinct regions of
      concentric growth outward from the central nidus, a small pebble. After initial
      growth, acidic colonic fluids permeated the stone inducing recrystallization and
      alteration of crystals closest to the nidus. A second growth event, when mineral
      crystallization was again favorable, produced an outer region of unaltered
      crystals at the rim. The mineral was identified as struvite (MgNH4PO4?6H2O) by
      powder X-ray diffraction (XRD) and Fourier transform infrared (FTIR)
      spectroscopy. Elemental analysis confirmed concentrations of P, Mg and N
      consistent with the struvite composition, and detected trace elements Fe (1050
      1860mgkg-1), Mn (262-280mgkg-1) and Zn (197-238mgkg-1). All elements were traced
      to dietary sources, with the Fe:Mn:Zn ratio of the enterolith consistent with
      that of the horse feed. X-ray absorption fine structure (XAFS) spectroscopy at
      the Zn K-edge revealed distorted ZnO4 tetrahedra located between crystallographic
      planes in the struvite structure forming bidentate linkages to struvite phosphate
      groups. Emplacement of Zn in structural cavities likely occurs during struvite
      crystallization. Trace elements and organic impurities increase susceptibility of
      the enterolith to heat-induced decomposition relative to pure struvite, which
      could be a consideration for treatment. Results reveal enterolith growth
      processes, composition and mechanisms of trace metal accumulation that can inform
      management and prevention of equine enteroliths.

PMID- 29173480
TI  - Changed expressions of N-methyl-d-aspartate receptors in the brains of rats and
      primary neurons exposed to high level of fluoride.
AB  - Expressions of N-methyl-d-aspartic acid receptors (NMDARs) in the brains of rats
      and primary neurons exposed to high fluoride were investigated. Sprague-Dawley
      rats were divided randomly into a fluorosis group (50ppm fluoride in the drinking
      water for 6 months) and controls (<0.5ppm fluoride) and the offspring from these
      rats sacrificed on postnatal days 1, 7, 14, 21 and 28. The primary cultured
      neurons from the hippocampus of neonatal rats were treated with 5 and 50ppm
      fluoride for 48h. NMDAR subunits at protein or mRNA levels were quantified by
      Western blotting or real-time PCR. The phosphorylated calmodulin-protein kinase
      II (CaMKII) was determined by Western blotting, concentration of Ca2+ in neurons
      by laser confocal microscopy and apoptosis by flow cytometry. In the brains of
      adult rats and pups as well as in primary neurons exposed to high fluoride, the
      mRNAs encoding GluN1 and GluN2B subunits and the corresponding proteins were
      elevated, the GluN3A lowered and the GluN2A unchanged. In addition, the level of
      phosphor-CaMKII was reduced, and Ca2+ influx and apoptosis enhanced in the brains
      of rats and cultured neurons exposed to high fluoride. The results indicate that
      such modifications may involve brain damage induced by chronic fluorosis.

PMID- 29173482
TI  - Excessive iodine status among Saharawi refugees.

PMID- 29173481
TI  - Manganese in blood cells as an exposure biomarker in manganese-exposed workers
      healthy cohort.
AB  - Elevated exposure to manganese (Mn) has long been a public health concern.
      However, there is currently no consensus on the best exposure biomarker. Here we
      aimed to investigate the exposomic characteristics of plasma metals among Mn
      exposed workers and explore the potential biomarkers of Mn exposure in the blood
      pool. First, total sixteen plasma metals (Calcium, Magnesium, Iron, Zinc, Copper,
      Selenium, Lead, Chromium, Arsenic, Manganese, Nickel, Molybdenum, Cadmium,
      Mercury, Thallium, and Cobalt) were determined among 40 occupationally Mn-exposed
      subjects. Second, Mn levels in both plasma and blood cells were detected among
      234 workers from the manganese-exposed workers healthy cohort (MEWHC),
      respectively. Analysis of plasma metal exposome showed that the plasma Mn
      concentrations were positively correlated to plasma Fe (r=0.361), Ni (r=0.363),
      Cr (r=0.486), and Hg (r=0.313) (all p<0.05). Mn concentrations in plasma were not
      significantly correlated to external exposure levels (ptrend=0.200), and it was
      further confirmed among the 234 subjects (ptrend=0.452). However, Mn
      concentrations in blood cells progressively increased as the external exposure
      dose increased (low-exposure group vs high-exposure group, median 11.53MUg/L vs
      20.41MUg/L, ptrend=0.001). Our results suggest that Mn in blood cells, but not
      plasma, could serve as a potential internal exposure biomarker. Larger validation
      studies are needed to establish the utility of this biomarker.

PMID- 29173483
TI  - Assessing the boron nutritional status by analyzing its cummulative frequency
      distribution in the hair and whole blood.
AB  - Boron is a non-essential ubiquitous trace element in the human body. The aim of
      this study was to assess boron nutritional status by analyzing boron frequency
      distribution in the long-term biological indicator tissue of hair and the short
      term biological indicator of whole blood. Hair samples were analyzed in 727
      apparently healthy subjects (263 ? and 464 ?) and the whole blood boron was
      analyzed in the random subsample of them (80 ? and 152 ?). Samples were analyzed
      by the ICP-MS at the Center for Biotic Medicine, Moscow, Russia. The adequate
      reference range for hair boron concentration was (MUg?g-1) 0.771- 6.510 for men
      and distinctly lower 0.472-3.89 for women; there was no detectable difference in
      the whole blood boron for the adequate reference range between men (0.020-.078)
      and women (0019-0.062). Boron may play an essential role in the metabolism of the
      connective tissue of the biological bone matrix.

PMID- 29173484
TI  - Strontium and oxidative stress in normal pregnancy.
AB  - BACKGROUND: Pregnancy brings about metabolic and oxidative changes that involve
      various trace elements and oxidative stress. Strontium (Sr) is a trace element
      scarcely studied in this context, although it has been suggested that it may play
      a role in the pathophysiology of preeclampsia. The main aim of this study was to
      evaluate Sr concentrations and oxidative status in normal pregnancy. METHODS: The
      study population included non-pregnant women (n=31), healthy pregnant women in
      the first (n=50), second (n=51) and third (n=53) trimesters of gestation, and
      women in postpartum period (n=31). Additionally, samples from another twenty
      pregnant women were obtained in the three trimesters. Strontium, copper, selenium
      and zinc were measured by inductively coupled plasma-mass spectrometry. Calcium
      (Ca), uric acid (UA), lipid peroxidation and total antioxidant activity (TAA)
      were measured by spectrophotometric assays. RESULTS: Strontium remained unchanged
      until the third trimester of pregnancy, in which significantly higher levels were
      found (p=0.001). The other elements showed diverse trends during pregnancy. Uric
      acid levels were significantly different in all groups (p<0.001), increasing
      gradually as the pregnancy progresses. In serial samples, there was a
      statistically significant positive correlation between Sr and gestational week of
      sampling (r=0.31, p=0.01), UA (r=0.40, p=0.001) and lipid peroxidation/TAA ratio
      (r=0.38, p=0.0002). Additionally, Sr correlated negatively with TAA (r=-0.40,
      p=0.0001). CONCLUSION: Strontium seems to play a physiological role in the
      oxidative status of the human organism. Further studies involving Sr and
      pathologies of pregnancy are warranted.

PMID- 29173485
TI  - High serum selenium levels are associated with impaired fasting glucose and
      elevated fasting serum glucose in Linyi, China.
AB  - BACKGROUND: The relationship between selenium level and impaired fasting glucose
      or elevated fasting serum glucose remains controversial. This study aimed to
      evaluate these associations in China. METHODS: This observational population
      study adopted a cluster sampling approach to enroll participants. Baseline
      information on selenium categories was tested using one-way analysis of variance
      and Kruskal-Wallis equality-of-populations rank tests. Multivariable logistic
      regression was used to investigate the association between serum selenium level
      and impaired fasting glucose or elevated fasting serum glucose. RESULTS: The mean
      serum selenium concentration was 121.5MUg/L which in a relatively high baseline
      Se status. Differences were observed among individuals with normal, impaired
      fasting glucose and elevated fasting serum glucose levels in their basic
      information, physical examination results and laboratory findings. After
      adjusting for their basic information, physical examination results and
      laboratory findings, compared with the low-selenium group, the high-selenium
      groups (124.9-143.9 and above 143.9MUg/L) had ORs for elevated fasting serum
      glucose of 2.31 (1.37-3.90) and 2.67 (1.59-4.48), respectively (both P<0.05). A
      sex-difference was observed, and a significant association between selenium
      levels and impaired fasting glucose was observed for males but not for females.
      CONCLUSIONS: The findings of this observational study suggest that relatively
      high selenium levels might be positively associated with elevated fasting serum
      glucose and relatively high selenium levels might be positively associated with
      impaired fasting glucose in men.

PMID- 29173486
TI  - Liver tissue trace element levels in HepB patients and the relationship of these
      elements with histological injury in the liver and with clinical parameters.
AB  - AIM: In this study, the relationship of liver tissue trace element concentrations
      with hepatitis B disease and the effects of several environmental factors were
      analysed. METHOD: The liver tissue concentrations of Al, Fe, Cd, Mn, Cr, Cu, Pb,
      Ni, Zn, Ag, and Co were evaluated in 92 patients with hepatitis B using the
      Inductively Coupled Plasma - Mass Spectrometry (ICP/MS) method in the analyses.
      The patients were divided into the following two groups: low-high Ishak
      histologic activity index (HAI) (0-6: Low Histologic Activity, 7-18: High
      Histologic Activity) and low-high fibrosis (FS) (Fibrosis 1,1,2 and Fibrosis
      3,4,5,6). The metal levels were compared between the groups. RESULTS: The Cd
      concentration was found to be statistically higher in the group with low HAI
      scores (p=0.019). The hepatic Cu concentration was found to be higher in women
      than in men (p=0.046). The hepatic Fe concentration was found to be higher in the
      group with increased FS compared to the group with decreased FS (p=0.033). Cd was
      found to be higher in patients who worked in positions involving exposure to
      heavy metals and in individuals with an ALT level above 40 IU/L (p=0.008).
      Several correlations have been found between the hepatic tissue metal levels in
      our study. In a linear regression analysis, Fe and Zn were found to be correlated
      with the fibrosis scores (p=<0.001 and p=0.029), and Cu was correlated with HAI
      (p=0.023). In the linear regression model, Ni (p=0.018) and Cr (p=0.011) were
      correlated with gender. There was a correlation between the hepatic Fe level and
      the location where hepatitis B patients were living (village/city) (p=0.001),
      frequency of fish consumption (p=0.045) and smoking (p=0.018) according to the
      linear regression analysis. Using a logistic regression analysis, Cr (p=0.029),
      Ni (p=0.031) and Pb (p=0.027) were found to be correlated with smoking habit, and
      Zn (p=0.010), Ag (p=0.026), Cd (p=0.007) and Al (p=0.005) were correlated with
      fish consumption. CONCLUSION: The liver tissue trace element levels are
      correlated with disease activity and histologic damage in patients with HepB
      disease. Additionally, smoking, the environment in which the patient works and
      the amount of fish consumption affect the accumulation of trace elements in the
      liver.

PMID- 29173488
TI  - Multi-elemental composition and antioxidant properties of strawberry tree
      (Arbutus unedo L.) honey from the coastal region of Croatia: Risk-benefit
      analysis.
AB  - The concentration of 23 major and trace elements, total phenolic content (TPC)
      and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were
      determined in nine samples of strawberry tree honey and compared to other types
      of unifloral honeys. The most abundant elements in strawberry tree honey were
      potassium, calcium, magnesium and sodium, ranging between 1276 and 2367, 95.2
      154, 14.4-74.4 and 13.4-64.3mg/kg, respectively. Strawberry tree honey had
      generally higher TPC (range: 0.314-0.522g GA/kg) and DPPH (1.94-4.45mM TE/kg)
      compared to other analysed unifloral honeys. A strong positive relationship was
      found between TPC and DPPH, TPC and concentration of homogentisic acid (HGA),
      chemical marker of strawberry tree honey, and between DPPH and HGA. Regarding
      daily intake of essential elements, strawberry tree honey can be considered
      nutritionally richer than the majority of unifloral honeys available in Croatia,
      while contribution to tolerable intake set for potentially toxic elements was
      very low, corresponding to pristine areas.

PMID- 29173487
TI  - Serum and whole blood Zn, Cu and Mn profiles and their relation to redox status
      in lung cancer patients.
AB  - Disturbed redox status may be critical to lung cancerogenesis, however little
      research has been conducted on general changes in total redox status in lung
      cancer. Levels and activities of antioxidants, especially enzymatic ones, are
      related to trace element concentration. Trace element status is often disturbed
      in cancers, however no studies concerning the association between redox and trace
      element status have been performed for lung cancer. We hypothesized that
      disturbed redox status in lung cancer patients is partially determined by trace
      elements while their distribution amongst blood compartments may differ compared
      to healthy subjects. Blood samples from lung cancer patients (n=44) and control
      subjects (n=44) were collected to assess redox and trace element status. Serum
      and whole blood Cu and Mn levels were determined with GF-AAS, and Zn-with F-AAS.
      In serum the total antioxidant status (TAS) was determined with the commercial
      kit TAS (Randox, UK), total oxidant status (TOS) was determined based on the
      method developed by Erel and the oxidative stress index (OSI) was calculated.
      Total protein (T-Prot), albumin (Alb), uric acid (UA) and total bilirubin (T-Bil)
      concentrations were measured with an auto-analyser (Konelab 20i,
      Thermoscientific, USA), SOD and CAT activity - with commercially available kits
      (Cayman, USA). The level of TAS, T-Prot, Alb, T-Bil, the activity of SOD, the
      concentration of whole blood Mn as well as serum and whole blood Zn were lower
      while TOS, OSI, serum Cu levels and serum Cu:Zn ratios were higher in lung cancer
      patients compared to the control group. In the lung cancer group TAS correlated
      positively with Alb and UA, serum Zn and negatively with whole blood Mn.
      Additionally, SOD positively correlated with the whole blood Mn and Cu:Zn ratio,
      while CAT - negatively with the whole blood Cu:Zn ratio. In the lung cancer sub
      group at clinical stage I-II, TOS additionally negatively correlated with whole
      blood Zn, and CAT negatively with serum Cu and Cu:Zn ratio. In advanced lung
      cancer, we found a positive correlation between TAS and serum Zn, and a negative
      one - with serum Cu:Zn ratio. We observed a similar correlation between
      endogenous non-enzymatic antioxidants and TAS in the control group, however
      considerably fewer correlations between trace elements and antioxidants were
      observed. This study supports the hypothesis that disturbed redox status in lung
      cancer patients is linked with alterations in trace element status regarding Zn,
      Mn and Cu. Moreover, the type of biological fluid influences both - alterations
      in the metal profile and relationships with redox status parameters.

PMID- 29173489
TI  - Bacterial exopolysaccharide (EPS)-coated ZnO nanoparticles showed high
      antibiofilm activity and larvicidal toxicity against malaria and Zika virus
      vectors.
AB  - In this study, a novel and effective approach was performed to synthesize ZnO
      nanoparticles (ZnO NPs) using the exopolysaccharides (EPS) from the probiotic
      strain Bacillus licheniformis Dahb1. EPS acted as reducing and stabilizing agent
      for the formation of EPS-ZnO NPs by co-precipitation method. Structural
      characterization was investigated by a surface plasma resonance centered at 375nm
      in UV-vis spectrum. FTIR spectrum exhibited functional groups with strong
      absorption peak at 3814.7-420cm-1. XRD showed the crystalline nature of EPS-ZnO
      NPs. TEM showed that the EPS-ZnO NPs were hexagonal in shape, with size within
      the range of 10-100nm. The presence of Zn was confirmed by EDX analysis.
      Antibacterial activity of EPS-ZnO NPs was demonstrated as 100MUg/ml significantly
      inhibited the effective growth control of Gram-negative (Pseudomonas aeruginosa
      and Proteus vulgaris) and Gram-positive (Bacillus subtilis and Bacillus pumilus)
      bacteria. Light microscopy and confocal laser scanning microscopy evidenced that
      the antibiofilm activity of EPS-ZnO NPs was higher against Gram-negative bacteria
      over Gram positive bacteria. EPS-ZnO NPs also inhibited the biofilm growth of
      Candida albicans at the concentration of 75MUg/ml. The hemolytic test showed low
      cytotoxicity of EPS-ZnO NPs at 5mg/ml. In addition, EPS-ZnO NPs achieved 100%
      mortality against third instars mosquito larvae of Anopheles stephensi and Aedes
      aegypti at very low doses. Moreover, histology studies revealed the presence of
      damaged cells and tissues in the mid-gut of treated mosquito larvae. The
      multipurpose properties of EPS-ZnO NPs revealed in the present study can be
      further considered for pharmaceutical, parasitological and entomological
      applications.

PMID- 29173490
TI  - Is a national registry of dyslipidaemia necessary?

PMID- 29173491
TI  - Results of the REVEAL study. Why Should we not welcome a new lipid lowering
      agent?

PMID- 29173492
TI  - Corrigendum to: Hepatitis C virus (HCV) infection of peripheral blood mononuclear
      cells in patients with type II cryoglobulinemia. Hum Immunol. 2013;74(12):1559
      62.

PMID- 29173493
TI  - Nanoparticles: "magic bullets" for targeting the immune system.

PMID- 29173494
TI  - The lymphocyte cytokinesis block micronucleus test in human populations
      occupationally exposed to vinyl chloride: A systematic review and meta-analysis.
AB  - Vinyl chloride (VC) is widely used in industry in the production of polyvinyl
      chloride (PVC), which is used to manufacture a large variety of materials. VC was
      classified as a known (Group 1) human carcinogen by IARC on the basis of
      increased risk for liver angiosarcoma and hepatocellular cancer, and the
      carcinogenicity of VC was shown to be mediated by a genotoxic mechanism.
      Following inhalation, the compound is rapidly absorbed and metabolized in the
      liver to the electrophilic metabolites chloroethylene-oxide and
      chloroacetaldehyde, which form DNA adducts that can be processed into point
      mutations in cancer-related genes detected in humans and rats exposed to VC. A
      number of genotoxicity biomarkers were applied in workers exposed to VC to detect
      early biological responses associated with the carcinogenesis process. The
      present systematic review analyzed the published studies in which the cytokinesis
      block micronucleus assay in peripheral lymphocytes (L-CBMN) was applied in VC
      exposed subjects. Thirteen out of fifteen retrieved studies performed in China
      showed increased MN frequencies (FR 1.92-3.98) associated with increased
      cumulative exposure or employment time. Twofold and more than threefold increases
      were detected in PVC-exposed workers exposed to a mean of 50ppm of VC in the
      former Yugoslavia and in South India, respectively. The meta-analysis of MN
      frequency from six eligible studies confirmed this tendency (pooled MR 2.32 - 95%
      CI 1.64-3.27). The benchmark dose lower limit for 10% excess risk (BMDL 10)
      calculated from three studies resulted in an estimated exposure limit of 0.03
      0.07mg/m3. Overall the results of this review showed the need for further
      studies, especially because PVC products from China may contain high levels of
      uncoupled VCM that could represent a source of exposure to workers and consumers.
      Moreover, the results underline the importance of re-evaluating the recommended
      exposure limits using new biomonitoring methods in addition to MN.

PMID- 29173495
TI  - Inflammation and the chemical carcinogen benzo[a]pyrene: Partners in crime.
AB  - Exposure to benzo[a]pyrene (B[a]P) is known to play a role in lung carcinogenesis
      and the underlying processes can be modified by the presence of inflammation. The
      inflammatory process can for instance enhance the concentration of reactive
      metabolites that bind to DNA and may also diminish DNA repair. Additionally,
      during the inflammatory process mediators are released that create a
      microenvironment which is suitable for further stimulation of cancer development.
      Various transcriptional pathways are activated by inflammation, including
      pathways that are mediated via nuclear factor kappa-light-chain-enhancer of
      activated B cells (NF-kappaB), signal transducer and activator of transcription 3
      (STAT-3), and hypoxia-inducible factor-1 (HIF-1). Crosstalk between these
      pathways and the aryl hydrocarbon receptor (AhR) occurs at multiple levels and
      thereby boosts B[a]P induced carcinogenesis. This review focuses on inflammatory
      mediators, including cytokines, chemokines and extracellular enzymes that
      modulate molecular events in B[a]P induced cancers.

PMID- 29173496
TI  - The interaction of iron and the genome: For better and for worse.
AB  - Iron, as an essential nutrient, and the DNA, as the carrier of genetic
      information which is physically compacted into chromosomes, are both needed for
      normal life and well-being. Therefore, it is not surprising that close
      interactions exist between iron and the genome. On the one hand, iron, especially
      when present in excess, may alter genome stability through oxidative stress, and
      may favor cell cycle abnormalities and the development of malignant diseases. The
      genome also receives a feedback signal from the systemic iron status, leading to
      promotion of expression of genes that regulate iron metabolism. Conversely, on
      the other hand, DNA mutations may cause genetic iron-related diseases such as
      hemochromatosis, archetype of iron-overload diseases, or refractory iron
      deficiency anemia (IRIDA).

PMID- 29173497
TI  - Breast cancer genetics in young women: What do we know?
AB  - Breast cancer (BC) in young women, generally defined in oncology as women who are
      40 years of age or younger, represents 2 out of 10 BC cases in developing
      countries. Several research studies, including genetic cancer panel tests, genome
      wide association studies, expression analyses and polymorphisms reports, have
      found that young women with BC exhibit a higher genetic susceptibility and
      specific genomic signature compared to postmenopausal women with BC. Thus,
      international guidelines recommend genetic counseling for this age population.
      This review presents the current state of the art of genetics and genomics with
      regards to young women with BC.

PMID- 29173498
TI  - Carcinogenic potential of sanguinarine, a phytochemical used in 'therapeutic'
      black salve and mouthwash.
AB  - Black salves are escharotic skin cancer therapies in clinical use since the mid
      19th century. Sanguinaria canadensis, a major ingredient of black salve
      formulations, contains a number of bioactive phytochemicals including the
      alkaloid sanguinarine. Despite its prolonged history of clinical use, conflicting
      experimental results have prevented the carcinogenic potential of sanguinarine
      from being definitively determined. Sanguinarine has a molecular structure
      similar to known polyaromatic hydrocarbon carcinogens and is a DNA intercalator.
      Sanguinarine also generates oxidative and endoplasmic reticulum stress resulting
      in the unfolded protein response and the formation of 8-hydroxyguanine genetic
      lesions. Sanguinarine has been the subject of contradictory in vitro and in vivo
      genotoxicity and murine carcinogenesis test results that have delayed its
      carcinogenic classification. Despite this, epidemiological studies have linked
      mouthwash that contains sanguinarine with the development of oral leukoplakia.
      Sanguinarine is also proposed as an aetiological agent in gallbladder carcinoma.
      This literature review investigates the carcinogenic potential of sanguinarine.
      Reasons for contradictory genotoxicity and carcinogenesis results are explored,
      knowledge gaps identified and a strategy for determining the carcinogenic
      potential of sanguinarine especialy relating to black salve are discussed. As
      patients continue to apply black salve, especially to skin regions suffering from
      field cancerization and skin malignancies, an understanding of the genotoxic and
      carcinogenic potential of sanguinarine is of urgent clinical relevance.

PMID- 29173499
TI  - Good value care: when less is more.

PMID- 29173500
TI  - Atrial fibrillation and type 1 diabetes.

PMID- 29173501
TI  - Atrial fibrillation and type 1 diabetes.

PMID- 29173502
TI  - Atrial fibrillation and type 1 diabetes - Authors' reply.

PMID- 29173504
TI  - Correction to Lancet Diabetes Endocrinol 2016; 4: 963-64.

PMID- 29173503
TI  - transCampus London-Dresden: a new model for international collaborative research.

PMID- 29173505
TI  - Correction to Lancet Diabetes Endocrinol 2017; 5: 864-76.

PMID- 29173506
TI  - Correction to Lancet Diabetes Endocrinol 2016; 4: 1004-16.

PMID- 29173507
TI  - Following new task instructions: Evidence for a dissociation between knowing and
      doing.
AB  - The ability to follow new instructions is crucial for acquiring behaviors and the
      cultural transmission of performance-related knowledge. In this article, we
      discuss the observation that successful instruction following seems to require
      both the capacity to understand verbal information, but also the ability to
      transform this information into a procedural format. Here we review the
      behavioral and neuroimaging literature on following new instructions and discuss
      how it contributes to our understanding of the functional mechanisms underlying
      instruction following. Based on this review, we distinguish three phases of
      instruction following. In the instruction phase, the declarative information of
      the task instruction is transformed into a task model consisting of a structured
      representation of the relevant condition-action rules. In the implementation
      phase, elements of this task model are transformed into a highly accessible state
      guiding behavior. In the application phase, the relevant condition-action rules
      are applied. We discuss the boundary conditions and capacity limits of these
      phases, determine their neural correlates, and relate them to recent models of
      working memory.

PMID- 29173509
TI  - Virtuous aging and existential vulnerability.
AB  - In its efforts to overcome problematic views that associate aging with inevitable
      decline, contemporary gerontology shows a tendency to focus predominantly on age
      related vulnerabilities that science may try to remedy and control. However,
      gerontology should also offer languages to address vulnerabilities that cannot be
      remedied because they intrinsically belong to the human condition. After all,
      these are increasingly radically encountered in later life and should therefore
      be reflected upon in the study of aging. Humanistic gerontology seems to be the
      most promising field to look for languages capable of contemplating such
      existential vulnerabilities. The potential contribution of philosophy in this
      field remains underdeveloped so far, however. This article therefore aims to
      introduce insights from the philosophical tradition to (humanistic) gerontology.
      More specifically, it focuses on the tradition of virtue ethics, arguing that
      virtue is a particularly relevant notion to explore in dealing with existential
      vulnerability in later life. The notion of virtue is clarified by discussing a
      selection of philosophical perspectives on this topic, by Aristotle, MacIntyre
      and Swanton. Next a brief overview will be given of some of the ways the notion
      of virtue has found its way into gerontological discourse so far. The article
      ends with an analysis of the merits of virtue-ethical discourse for the study of
      aging and later life, and pleads for more inclusion of philosophical ideas such
      as virtue in gerontology, as these can enrich our conceptual frameworks and help
      us relate to deep existential questions regarding the experience of aging.

PMID- 29173510
TI  - Understanding functional ability: Perspectives of nurses and older people living
      in long-term care.
AB  - The functional ability of older people has come to play a significant role in
      their care. Policies and public debate promote active aging and the need to
      maintain functioning in old age, including among older people living in long-term
      care. This study explores the meanings given to functional ability in the
      interview talk of long-term care nurses (n=24) and older people living in long
      term care (n=16). The study is based on discourse analysis and positioning
      theory. In this study, accounts of functioning differed between nurses and older
      residents. For the nurses, functional ability was about the basic functions of
      everyday life, and they often used formal and theoretical language, whereas for
      older long-term care residents, functional ability was a more versatile concept.
      Being active was promoted, particularly in the nurses' talk but also sometimes in
      residents' talk, thereby reflecting the public discourse about functioning. In
      their talk, the nurses positioned themselves in relation to functional ability as
      competent professionals and active caregivers. In residents' talk, we found three
      positions: an active individual taking care of him or herself, a recipient of
      help, and a burden to nurses. To move in a direction that promotes activity and
      rehabilitative care, a better understanding of older people's individual needs
      and their own views of functional ability is needed.

PMID- 29173511
TI  - Evaluating dementia home care practices: The reification of care norms.
AB  - This critical ethnographic study examined how power relations shape the nature
      and enactment of caregivers' evaluation of home-based dementia care practices. As
      the home care sector continues to evolve and prepare itself as a key element in
      caring for people living with dementia and their families, this study grounds our
      understanding of how dementia home care practices are enacted and evaluated,
      particularly at the interface of formal and familial caregiving. The critical
      finding from our data is that not all evaluations of care practices were
      considered equally meaningful or relevant, and, moreover, their significance
      depended on whether the evaluation was made by someone in a position of power.
      Renewed awareness of and attention to power relations, such as class and gender,
      are implicated in the evaluation of care practices. Consequently, challenging how
      power is enacted in ways that (re)produces and reifies care norms is vital in
      order to foster equitable and supportive partnerships in home-based dementia
      care.

PMID- 29173512
TI  - From home to 'home': Mapping the caregiver journey in the transition from home
      care into residential care.
AB  - Family caregivers play a pivotal role in supporting the functional independence
      and quality of life of older relatives, often taking on a wide variety of care
      related activities over the course of their caregiving journey. These activities
      help family members to remain in the community and age-in-place for as long as
      possible. However, when needs exceed family capacities to provide care, the older
      family member may need to transition from one care environment to another (e.g.,
      home care to nursing home care), or one level of care to another (from less
      intense to more intensive services). Drawing upon qualitative interview data
      collected in a populous health region in British Columbia, Canada, this study
      explores the roles and responsibilities of family caregivers for family members
      making the care transition from home care to residential care. A thematic
      analysis of the interview transcripts resulted in the development of a conceptual
      framework to characterize the "Caregiver Journey" as a process that could be
      divided into at least three phases: 1) Precursors to transition - recognizing
      frailty in family members and caregivers prior to transition; 2) Preparing to
      transition into residential nursing home care (RC) and 3) Post-transition:
      Finding a new balance - where caregivers adjust and adapt to new caregiving
      responsibilities. Our analyses revealed that the second phase is the most complex
      involving a consideration of the various activities, and roles that family
      caregivers take on to prepare for the care transition including: information
      gathering, advocacy and system navigation. We conclude that there is a need for
      family caregivers to be better supported during care transitions; notably through
      ongoing and enhanced investments in strategies to support caregiver communication
      and education.

PMID- 29173508
TI  - What's in a word? How instructions, suggestions, and social information change
      pain and emotion.
AB  - Instructions, suggestions, and other types of social information can have
      powerful effects on pain and emotion. Prominent examples include observational
      learning, social influence, placebo, and hypnosis. These different phenomena and
      their underlying brain mechanisms have been studied in partially separate
      literatures, which we discuss, compare, and integrate in this review. Converging
      findings from these literatures suggest that (1) instructions and social
      information affect brain systems associated with the generation of pain and
      emotion, and with reinforcement learning, and that (2) these changes are mediated
      by alterations in prefrontal systems responsible for top-down control and the
      generation of affective meaning. We argue that changes in expectation and
      appraisal, a process of assessing personal meaning and implications for
      wellbeing, are two potential key mediators of the effects of instructions and
      social information on affective experience. Finally, we propose a tentative model
      of how prefrontal regions, especially dorsolateral and ventromedial prefrontal
      cortex may regulate affective processing based on instructions and socially
      transmitted expectations more broadly.

PMID- 29173513
TI  - Enabling at-homeness for residents living in a nursing home: Reflected experience
      of nursing home staff.
AB  - Older people are often living the last period of their lives in institutions such
      as nursing homes. Knowledge of this period, specifically related to at-homeness
      which can be described as wellbeing in spite of illness and has been regarded as
      one of the goals in palliative care, has been very little researched in the
      context of nursing homes and the experience of nursing home staff. The aim of
      this study was to explore the experiences of nursing home staff of how to enable
      at-homeness for residents. Qualitative interpretive description methodology
      guided the design. The data generation was conducted in winter 2014-2015, when
      seven repetitive reflective group discussions with staff in a nursing home were
      held. The results show five patterns for how healthcare staff enabled at-homeness
      for the residents: Striving to know the resident, Showing respect for the
      resident's integrity, Creating and working in family-like relationships, Helping
      to find a new ordinariness and Preparing and making plans to ensure continuity.
      Nursing home staff seem to have collegial knowledge of how to enable at-homeness
      for the residents in a nursing home. Close relationships with respect for the
      resident's integrity stand out as enabling at-homeness.

PMID- 29173514
TI  - Is longevity a value for older adults?
AB  - Longevity is an aspiration at the population level, a goal of public health
      policy and research. In the later decades of life, longevity goals also deserve
      scrutiny at the personal level to understand whether people welcome longer lives.
      Contradictory preferences could be expected, both the embrace of longevity and
      hesitation. The desire for extended life was examined using qualitative
      interviews in parallel designs among 90 persons aged 62 and older at sites in
      Germany, China, and the United States. Just over one third of the participants
      declined to express aspirations for longer life, some because they felt that
      their lives had reached a stage of completion and some as a form of fate
      acceptance. A larger number did indeed want extended lives but less than half
      estimated an amount of time that they desired. Moreover, there was strong opinion
      that longer lives were desirable only if current or acceptable levels of health
      were maintained. These replies indicate that future time is welcome so long as it
      occurs in the "third age" of independent living and not in the "fourth age" of
      vulnerability and decline. Replies also reveal that many older adults in these
      three cultures conceptually map the future not as a smooth continuum of time but
      rather as segmented into states, one kind of which is wanted and one which is
      not.

PMID- 29173515
TI  - Precarity in late life: Understanding new forms of risk and insecurity.
AB  - Population aging and longevity in the context of declining social commitments,
      raises concerns about disadvantage and widening inequality in late life. This
      paper explores the concept of precarity as a means to understand new and
      sustained forms of risk and insecurity that affect late life. The article begins
      with a review of the definition and uses of precarity in a range of scholarly
      fields including social gerontology. It then draws on illustrations from three
      locations of experience including older women, aging with a disability, and the
      foreign-born, to outline how precarity renders visible the disadvantages carried
      into late life, and new insecurities that emerge at the moment of needing care in
      the context of austerity. The argument being put forward is that precarity can be
      used to illustrate how risks and insecurities, experienced over time, in
      longevity, and the context of austerity, can deepen disadvantage. This lens thus
      holds the potential to challenge individual interpretations of risk, and situate
      experiences of disadvantage in the economic and political context. We conclude
      that contemporary conditions of austerity and longevity intersect to produce and
      sustain risk and disadvantage into late life.

PMID- 29173516
TI  - Use of Complementary and Alternative Medicine in Inflammatory Bowel Disease
      Around the World.
AB  - Use of complementary sand alternative medicine (CAM) is common among patients
      with inflammatory bowel disease (IBD). CAM can be broadly categorized as whole
      medical systems, mind-body interventions, biologically based therapies,
      manipulative and body-based methods, and energy therapies. Most do not use it to
      treat IBD specifically, and most take it as an adjunct to conventional therapy
      not in place of it. However, patients are frequently uncomfortable initiating a
      discussion of CAM with their physicians, which may impact adherence to
      conventional therapy. A greater emphasis on CAM in medical education may
      facilitate patient-physician discussions regarding CAM.

PMID- 29173518
TI  - Dietary Therapies in Pediatric Inflammatory Bowel Disease: An Evolving
      Inflammatory Bowel Disease Paradigm.
AB  - Nutrition has long been recognized as a critical component in the treatment of
      pediatric inflammatory bowel disease (IBD). Formerly, nutritional interventions
      have focused on targeting improved weight gain and linear growth, as well as
      correction of micronutrient deficiencies. Recently, there has been growing
      interest and study of dietary interventions for induction and maintenance of
      remission. In addition to exclusive enteral nutrition, successes have been
      achieved with specific exclusion diets. This article evaluates current literature
      regarding the role of diet and nutrition in pathogenesis of disease, as well as
      the role of diet as primary therapy for pediatric IBD.

PMID- 29173520
TI  - Probiotics in Inflammatory Bowel Disease.
AB  - Evidence indicates that the gut microbiota and/or interactions between the
      microbiota and the host immune system are involved in the pathogenesis of
      inflammatory bowel disease (IBD). Strategies that target the microbiota have
      emerged as potential therapies and, of these, probiotics have gained the greatest
      attention. Data derived from animal models of IBD have revealed the potential of
      several bacterial strains to modify the natural history of IBD. However, thought
      there is some evidence for efficacy in ulcerative colitis and in pouchitis, in
      particular, there has been little indication that probiotics exert any benefit in
      Crohn disease. More targeted approaches involving live bacteria, genetically
      modified bacteria, and bacterial products are now being evaluated.

PMID- 29173521
TI  - Prebiotics and Inflammatory Bowel Disease.
AB  - Dietary fiber, specifically prebiotics, is the primary source of energy for the
      gut microbiota and thus has the potential to beneficially modify microbiota
      composition. Prebiotics have been used in both in vitro studies and with animal
      models of colitis with largely positive results. Human studies are few and have
      been conducted with only a few select prebiotics, primarily fructan-containing
      fibers. Although disease activity and inflammatory markers have improved, more
      needs to be learned about the specific prebiotic compounds and how they can be
      used to best improve the gut microbiota to counter changes induced by
      inflammatory bowel disease.

PMID- 29173519
TI  - Diet as a Therapeutic Option for Adult Inflammatory Bowel Disease.
AB  - There are many mechanisms to explain how food may drive and ameliorate
      inflammation. Although there are no consistent macronutrient associations
      inflammatory bowel disease (IBD) development, many exclusion diets have been
      described: IgG-4 guided exclusion diet; semivegetarian diet; low-fat, fiber
      limited exclusion diet; Paleolithic diet; Maker's diet; vegan diet; Life without
      Bread diet; exclusive enteral nutrition (EEN), the Specific Carbohydrate Diet
      (SCD) and the low FODMAP diet. The literature on diet and IBD is reviewed with a
      particular focus on EEN, SCD, and low FODMAP diets. Lessons learned from the
      existing observations and strengths and shortcomings of existing data are
      presented.

PMID- 29173522
TI  - Vitamins and Minerals in Inflammatory Bowel Disease.
AB  - Indiscriminate use of multivitamin/mineral supplements in the general population
      may be misguided, but patients with chronic Inflammatory Bowel Diseases (IBD)
      should be monitored and compensated for nutritional deficiencies. Mechanistic
      links between vitamin/mineral deficiencies and IBD pathology has been found for
      some micronutrients and normalizing their levels is clinically beneficial.
      Others, like vitamin A, although instinctively desirable, produced disappointing
      results. Restoring normal levels of the selected micronutrients requires elevated
      doses to compensate for defects in absorptive or signaling mechanisms. This
      article describes some aspects of vitamin and mineral deficiencies in IBD, and
      summarizes pros and cons of supplementation.

PMID- 29173523
TI  - Herbs and Inflammatory Bowel Disease.
AB  - Although herbal preparations are widely used by patients with inflammatory bowel
      disease (IBD), evidence for their efficacy is limited and they may not always be
      safe. Mainly small studies of varying quality have suggested that several herbal
      preparations could be of benefit in IBD, but larger better-designed trials are
      needed to establish their place in inducing and maintaining remission. Patients
      and health care workers need to be made more aware of the limitations and risks
      of using herbal products for IBD.

PMID- 29173524
TI  - Fecal Transplant in Inflammatory Bowel Disease.
AB  - Patients with inflammatory bowel disease (IBD) have differences in their
      gastrointestinal microbiome compared with healthy individuals, although it is
      unclear whether this is a cause or consequence of chronic inflammation. There is
      hope that manipulation of the gut microbiome through fecal microbiota transplant
      (FMT), commonly used to treat patients with Clostridium difficile infection, may
      also be an effective therapy in IBD. This article reviews the evidence supporting
      FMT in IBD, including case reports, case series, and randomized controlled
      trials. The article also focuses on questions of safety and speculates on the
      future of this therapy.

PMID- 29173525
TI  - The Brain-Gut Axis and Stress in Inflammatory Bowel Disease.
AB  - The brain-gut axis serves as a circuit that incorporates the human experience,
      the state of mind, the gut microbiome, and the immune response that ultimately
      drives the phenotypic expression of inflammatory bowel disease (IBD). There are
      several biological pathways through which stress can play a deleterious role,
      including through increasing intestinal permeability, which can facilitate
      intestinal translocation of bacteria. Stress has an impact on symptoms in IBD;
      however, there is limited evidence that stress triggers increased intestinal
      inflammation. Although attention to stress and psychiatric comorbidity is
      important in the management of IBD, there are few clinical trials to direct
      management.

PMID- 29173517
TI  - Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota
      Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.
AB  - The human gut microbiome exerts a major impact on human health and disease, and
      therapeutic gut microbiota modulation is now a well-advocated strategy in the
      management of many diseases, including inflammatory bowel disease (IBD).
      Scientific and clinical evidence in support of complementary and alternative
      medicine, in targeting intestinal dysbiosis among patients with IBD, or other
      disorders, has increased dramatically over the past years. Delivery of
      "artificial" stool replacements for fecal microbiota transplantation (FMT) could
      provide an effective, safer alternative to that of human donor stool.
      Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and
      future investigations are essential.

PMID- 29173527
TI  - Mindfulness-Based Interventions in Inflammatory Bowel Disease.
AB  - Mindfulness-based interventions may be beneficial psychosocial treatments for
      improving the health and well-being of patients with inflammatory bowel disease.
      This article reviews eight studies, assessing seven psychosocial interventions,
      which include mindfulness and/or meditation components. Strongest effects of the
      interventions were found in quality of life and anxiety/depression, with
      inconsistent or minimal changes in other psychosocial areas, such as perceived
      stress and in disease-related outcomes and other physiologic functioning.
      Mindfulness interventions for patients with inflammatory bowel disease may be a
      supplemental treatment option to improve quality of life and distress in this
      population, although results are preliminary and interventions require additional
      testing.

PMID- 29173526
TI  - Psychological Considerations and Interventions in Inflammatory Bowel Disease
      Patient Care.
AB  - The presence of psychological comorbidities, specifically anxiety and depression,
      is well documented in inflammatory bowel disease (IBD). The drivers of these
      conditions typically reflect 4 areas of concern: disease impact, treatment
      concerns, intimacy, and stigma. Various demographic and disease characteristics
      increase risk for psychological distress. However, the risk for anxiety and
      depression is consistent throughout IBD course and is independent of disease
      activity. Early intervention before psychological distress becomes uncontrolled
      is ideal, but mental health often is unaddressed during patient visits.
      Understanding available psychological treatments and establishing referral
      resources is an important part of the evolution of IBD patient care.

PMID- 29173528
TI  - Massage Acupuncture, Moxibustion, and Other Forms of Complementary and
      Alternative Medicine in Inflammatory Bowel Disease.
AB  - Complementary and alternative medicine is frequently used by inflammatory bowel
      disease (IBD) patients; most common are massage, acupuncture, and moxibustion
      therapy. Massage therapy is poorly studied in IBD patients; therefore, its
      benefits remain unknown. Acupuncture and moxibustion therapy have been shown to
      improve inflammation and symptoms in animal and human studies. However, current
      clinical trials of acupuncture and moxibustion are of insufficient quality to
      recommend them as alternative therapy. Nonetheless, because these therapies seem
      generally to be safe, they may have a role as complementary to conventional
      therapy.

PMID- 29173529
TI  - Sleep and Circadian Hygiene and Inflammatory Bowel Disease.
AB  - There is increasing evidence that sleep and circadian disruption can worsen the
      disease course in inflammatory bowel disease (IBD). Sleep and circadian
      disruption are prevalent in society and are associated with worse outcomes in
      IBD. Emerging research suggests sleep and circadian disruption can impact key
      components in IBD disease flares, including intestinal permeability,
      translocation of bacterial endotoxins, intestinal dysbiosis, and proinflammatory
      cytokines. Much of this research has been conducted in animal models. There is a
      clear need for large randomized controlled trials in human patients with IBD,
      where the potential for chronotherapeutic strategies to improve disease course
      can be tested.

PMID- 29173530
TI  - Exercise and Inflammatory Bowel Disease: Insights into Etiopathogenesis and
      Modification of Clinical Course.
AB  - There is sparse information regarding exercise and inflammatory bowel disease
      (IBD). Furthermore, the importance of regular exercise in the optimal management
      of IBD has not received attention in guidelines and is often overlooked by
      practitioners. This article summarizes evidence regarding health benefits of
      exercise, guidelines regarding exercise in the general population and chronic
      inflammatory disorder populations, limitations regarding exercise capacity in
      patients with IBD, the association of lack of exercise with IBD pathogenesis, the
      role of exercise in beneficially modulating IBD clinical course, and
      extraintestinal benefits of exercise in patients with IBD.

PMID- 29173531
TI  - The Practical Pros and Cons of Complementary and Alternative Medicine in
      Practice: Integrating Complementary and Alternative Medicine into Clinical Care.
AB  - Complementary and alternative medicine (CAM) is changing health care for
      individuals with inflammatory bowel disease. The move toward increasing patient
      autonomy and addressing lifestyle and psychosocial factors contributes to this
      shift. Numerous clinics and centers are offering new models to incorporate these
      elements. There is need for better and more robust data regarding CAM efficacy
      and safety. CAM offers a test kitchen for new approaches to care and care
      delivery, which are now being developed and studied, and has the possibility to
      affect patient quality of life, disease morbidity, cost, and use of health care.

PMID- 29173532
TI  - Complementary and Alternative Treatments Are Needed to Enhance the Care of the
      Inflammatory Bowel Disease Patient.

PMID- 29173533
TI  - Strongyloides westeri worm and egg counts in naturally infected young horses.
AB  - Strongyloides westeri is a threadworm parasite found in the small intestine
      mainly in foals at up to about 4 months of age. This parasite is associated with
      small intestinal enteritis and diarrhea as well as skin irritation and a clinical
      syndrome called "frenzied behavior" due to percutaneous invasion. The aim of this
      study was to investigate S. westeri parasite burdens in age groups older than the
      initial lactogenic transmission phase. Secondary aims were to examine the impact
      of host age and gender on worm burden and egg output in naturally infected foals.
      Thirteen foals were enrolled in the study, exposed to natural infection with S.
      westeri and were humanely euthanized at ages ranging from 89 to 221days old. Egg
      counts per gram of feces were determined using the Mini-FLOTAC method. Worms were
      retrieved from the mucosa of the anterior half of the small intestine using a
      digestion method and enumerated. The foals were all observed to be healthy with
      no signs of parasitic disease. Foals at 4-5 months of age had significantly
      higher S. westeri worm and egg counts compared to those aged 6-8 months (p<0.05).
      Fecal egg counts were significantly associated with worm counts (p=0.0045). While
      egg and worm counts declined markedly in the 6-8 month age range, they were not
      eliminated completely. This could either reflect a new infection acquired orally
      or transcutaneously, or a subset of adult intestinal parasites acquired via the
      lactogenic route and surviving for longer time periods. This study provided new
      information about S. westeri infection patterns in young horses at 4-8 months of
      age.

PMID- 29173534
TI  - Canine neutrophils activate effector mechanisms in response to Leishmania
      infantum.
AB  - Canine leishmaniosis caused by L. infantum is a severe zoonotic disease. Although
      macrophages are the definitive host cells, neutrophils are the first cells to
      encounter the parasite soon after its inoculation in the dermis by the
      phlebotomine vector. To study the interaction of dog neutrophils and L. infantum
      promastigotes, blood neutrophils were isolated from healthy donors and the
      infection was established in vitro. In the majority of the dogs, L. infantum was
      efficiently phagocytized by neutrophils, and oxidative (superoxide production)
      and non-oxidative (neutrophil elastase exocytosis) intracellular effector
      mechanisms were activated, but the release of neutrophil extracellular traps was
      minimized. Furthermore, promastigotes and culture supernatants induced neutrophil
      migration, but the prior contact with Leishmania inhibits chemotaxis, which might
      contribute to neutrophil retention at the inoculation site. Neutrophil-parasite
      interaction resulted in a decrease in parasite viability, although some
      intracellular promastigotes survive and maintain their proliferative capacity.
      These findings indicate that dog neutrophils are competent effector cells able to
      control the initial L. infantum infection. However, some parasites evade
      intracellular effector mechanisms and can be transferred to the definitive host
      cell, the macrophage, contributing to the development of canine leishmaniosis.

PMID- 29173535
TI  - Ticks circulate Anaplasma, Ehrlichia, Babesia and Theileria parasites in North of
      Iran.
AB  - Ticks serve as important vectors of some pathogens of medical importance all over
      the world and identification of their rate of infection plays an important role
      for further control of diseases. In the current study, we investigated on ticks
      collected from north of Iran where raising and caring livestock are the main task
      of the people in order to find evidences of infection of Babesia, Theileria,
      Anaplasma and Ehrlichia microbial agents. Totally, 609 hard tick species from two
      genera Hyalomma and Rhipicephalus including; Hy. scupense, Hy. dromedarii, Hy.
      rufipes, Hy. marginatum, Hy. asiaticum, Hy. anatolicum, R. bursa, R. sanguineus
      and R. turanicus were identified. Molecular analysis revealed the presence of
      Anaplasma, Ehrlichia, Babesia and Theileria microorganism agents in all collected
      tick species except Hy. asiaticum and R. turanicus. To the best of our knowledge,
      this is the first report on identification of B. occultans in Hyalomma anatolicum
      and B. ovis in Hyalomma sp in Iran.

PMID- 29173536
TI  - Molecular confirmation of Sarcocystis gigantea in a naturally infected sheep in
      Argentina: A case report.
AB  - The work describes a case of Sarcocystis gigantea infection in a 3-years-old
      Corriedale ewe from Buenos Aires Province, Argentina. The ewe was found dead with
      a poor body condition. Pathological and molecular studies were carried out in
      order to try and confirm the causative agent of the infection. At necropsy,
      approx. 100 whitish elliptic (3-5mm to 5-8mm) macrocysts with a hard consistency
      were observed along the esophageal and pharyngeal muscular layers.
      Microscopically, the macrocysts consisted of an eosinophilic wall, internal septa
      originated from the eosinophilic wall and basophilic parasitic cells were located
      among the septa. The sarcocysts were identified molecularly through PCR
      amplification and sequencing of a short segment of the 18S rRNA gene. Sequence
      analysis of the amplified DNA demonstrated 100% identity to S. gigantea sequences
      previously published. To our knowledge this is the first molecular confirmation
      of S. gigantea infection in sheep in the Americas.

PMID- 29173537
TI  - A newly described strain of Eimeria arloingi (strain A) belongs to the
      phylogenetic group of ruminant-infecting pathogenic species, which replicate in
      host endothelial cells in vivo.
AB  - Coccidiosis caused by Eimeria species is an important disease worldwide,
      particularly in ruminants and poultry. Eimeria infection can result in
      significant economic losses due to costs associated with treatment and slower
      growth rates, or even with mortality of heavily infected individuals. In goat
      production, a growing industry due to increasing demand for caprine products
      worldwide, coccidiosis is caused by several Eimeria species with E. arloingi and
      E. ninakohlyakimovae the most pathogenic. The aims of this study were genetic
      characterization of a newly isolated European E. arloingi strain (A) and
      determination of phylogenetic relationships with Eimeria species from other
      ruminants. Therefore, a DNA sequence of E. arloingi strain (A) containing 2290
      consensus nucleotides (the majority of 18S rDNA, complete ITS-1 and 5.8S
      sequences, and the partial ITS-2) was amplified and phylogenetic relationship
      determined with the most similar sequences available on GenBank. The phylogenetic
      tree presented a branch constituted by bovine Eimeria species plus E. arloingi,
      and another one exclusively populated by ovine Eimeria species. Moreover, E.
      arloingi, E. bovis and E. zuernii, which all replicate in host intestinal
      endothelial cells of the lacteals, were found within the same cluster. This study
      gives new insights into the evolutionary phylogenetic relationships of this newly
      described caprine Eimeria strain and confirmed its close relationship to other
      highly pathogenic ruminant Eimeria species characterized by macromeront formation
      in host endothelial cells of the central lymph capillaries of the small
      intestine.

PMID- 29173538
TI  - Serological detection of Ascaris suum at fattening pig farms is linked with
      performance and management indices.
AB  - The aim of the present study was to determine the association between the
      presence of Ascaris suum at fattening pig farms, using different serological
      methods and the percentage of affected livers at slaughter, with performance and
      management indices. In total, 21 fattening pig farms from the North of Spain were
      included in the study. Serum samples were collected from pigs at slaughter and
      analysed for the presence of anti-Ascaris antibodies. For this, two different
      ELISAs were used. The first was based on the antibody recognition of the A. suum
      haemoglobin (As-Hb) molecule whereas the second test used the total extract of A.
      suum lung stage L3. The serological results were subsequently correlated with the
      percentage of condemned livers at slaughter, management practices and technical
      performance parameters including average daily gain (ADG) and feed conversion
      ratio (FCR). According to the data from the slaughterhouse, 12 out of the 21
      farms had livers condemned due to liver white spots. A total of 10 farms (48%)
      had an average optical density ratio (ODr) exceeding the test cutoff when the As
      Hb ELISA was used. This number increased to 18 farms (81%) when using the As-Lung
      L3 ELISA. The average ODr of the farms on both ELISAs correlated positively with
      the percentage of affected livers (P<0.01). Only the average ODr values obtained
      with the As-Lung-L3 ELISA were positively correlated with the FCR (P<0.01). No
      correlation was found between percentage of affected livers or serology and the
      ADG. In relation to management practices, farms with greater than or equal to 50%
      slatted flooring and that applied the 'all-in/all-out' flow system showed a lower
      percentage of liver condemnations (P<0.01), lower average ODr results on the As
      Lung-L3 ELISA (P<0.05) and lower FCR (P<0.01) compared with those with less than
      50% slatted flooring. This study emphasizes that serology is a promising
      diagnostic tool for diagnosing ascariasis at fattening pig farms. It also
      supports earlier findings that the presence of A. suum can have a significant
      negative impact on farm productivity and that stable infrastructure or management
      practices can have a considerable impact on the control of this parasite.

PMID- 29173539
TI  - Leishmania infantum-specific IFN-gamma production in stimulated blood from dogs
      with clinical leishmaniosis at diagnosis and during treatment.
AB  - There is limited data regarding Leishmania infantum specific T cell mediated
      immunity in naturally infected sick dogs at the time of diagnosis and during anti
      Leishmania treatment. Our aim was to investigate the kinetics of L. infantum
      specific IFN-gamma production in dogs with leishmaniosis at the time of diagnosis
      and during treatment and to correlate it with specific L. infantum antibodies,
      blood parasitemia and clinicopathological findings. Thirty-four dogs were
      diagnosed with leishmaniosis based on physical examination, routine laboratory
      tests and L. infantum-specific antibody levels by quantitative ELISA. Heparinized
      whole blood was stimulated with L. infantum soluble antigen (LSA) and
      concanavalin A (ConA) and incubated for 5days. IFN-gamma concentration was
      evaluated in supernatants of stimulated blood using a commercial sandwich ELISA.
      Leishmania real-time PCR was also performed for assessing blood parasitemia. Dogs
      were treated with meglumine antimoniate and allopurinol. Sixteen dogs were
      classified as IFN-gamma non-producers after LSA stimulation (mean+/-SD: 0+/
      0pg/mL) and 18 dogs as IFN-gamma producers (mean+/-SD: 2885.3+/-4436.1pg/mL) at
      the time of diagnosis (P<0.0001). IFN-gamma non-producers were classified in a
      more severe clinical staging than IFN-gamma producers that presented a mild to
      moderate clinical staging (P=0.03). In the IFN-gamma non-producer group,
      production of IFN-gamma after LSA stimulation was significantly increased during
      treatment especially at day 365 (P=0.018) together with clinical improvement when
      compared with day 0. In contrast, IFN-gamma producers maintained their IFN-gamma
      production after LSA stimulation and no statistically significant changes were
      found during treatment follow-up. At diagnosis, IFN-gamma non-producers showed a
      significantly higher blood parasitemia versus IFN-gamma -producers (P=0.005). IFN
      gamma non-producers drastically reduced blood parasitemia to minimum values at
      day 365 when compared with day 0 (P=0.017). No significant differences were found
      at day 365 in blood parasitemia of IFN-gamma producers compared to pre-treatment.
      At diagnosis, L. infantum specific antibodies were higher in IFN-gamma non
      producers than IFN-gamma producers (P=0.014). A marked reduction of antibody
      levels was found at day 365 when compared with day 0 in IFN-gamma non-producers
      (P=0.005) and producers (P=0.001). These results demonstrate that IFN-gamma
      concentration increases with long-term anti-Leishmania treatment together with
      clinical improvement in dogs that do not produce IFN-gamma at diagnosis. Together
      with clinical recovery, reduction in blood parasitemia and L. infantum specific
      antibodies, tracking IFN-gamma concentration could constitute an important
      prognostic tool for immune monitoring in CanL.

PMID- 29173540
TI  - Characterization of multiple life stages of two Australian Fasciola hepatica
      isolates in sheep.
AB  - Information on the susceptibility status of Fasciola hepatica isolates is lacking
      in the literature, even for those isolates considered to be laboratory reference
      strains. Four controlled efficacy studies were conducted on two Fasciola hepatica
      isolates from Australia, viz. 'Oberon' and 'Sunny Corner' with treatment at
      either 2, 6 or 10 weeks post-infection (wpi) as defined in each study. Fluke
      burdens and examination of livers occurred at necropsy in weeks 12 (Study 1) or
      13 (Studies 2, 3 and 4) post-infection. The triclabendazole (TCBZ) resistance
      status of the Oberon isolate was confirmed in 6 and 10-week old F. hepatica,
      utilizing the drug alone (Fasinex; 71.5% and 31.1%, respectively) and in
      combination with oxfendazole (Flukazole C; 79.9% and 0%, respectively). The
      susceptibility of this isolate to albendazole, as well as salicylanilide and
      sulphonamide drugs was confirmed. The Sunny Corner isolate was confirmed as
      susceptible to TCBZ (>99% all stages) and closantel (>90% at >=6 wpi).

PMID- 29173541
TI  - Progesterone inhibits the in vitro L3/L4 molting process in Haemonchus contortus.
AB  - We evaluated the direct effects of progesterone on the morphology, maturation and
      behavior of Haemonchus contortus larvae in vitro. The presence and location of
      possible progesterone receptors in these larvae were also determined. The
      addition of 8ng/mL of progesterone to larval cultures over 10days reduced larval
      enlargement, while the addition of 160ng/mL of the hormone increased the
      enlargement. Up to 62% and 65% of the H. contortus larvae molted from third-stage
      larvae (L3) to fourth-stage larvae (L4) when cultured in RPMI-1640 media without
      hormone for 5 and 10days, respectively. The addition of different progesterone
      concentrations (1, 8, 16, 80 and 160ng/mL) to the larval cultures significantly
      inhibited the molting process within the same periods. The addition of 8ng/mL or
      higher progesterone concentrations to the cultures significantly increased larval
      motility (p<0.05) compared with unstimulated larvae. Flow cytometry showed the
      expression of progesterone receptors (P4-R) in 15% of the cells from newly
      isolated H. contortus larvae. When the larvae were cultured for 5days in the
      presence of the hormone, the percentage of P4-R+ cells remained the same. In
      contrast, unstimulated larvae showed a significant reduction in the number of P4
      R+ cells. Using confocal microscopy, a greater concentration of P4-Rs was
      immunolocated in the anterior portion of the alimentary tract of the larvae,
      suggesting that the cells in this region are targeted by the hormone. The results
      of the present study show that H. contortus larvae have possible P4-Rs and
      respond to this hormone by inhibiting their molting process, thereby suggesting
      the participation of progesterone in the larval arrest phenomenon.

PMID- 29173542
TI  - Regression models to assess the risk factors of canine gastrointestinal
      parasitism.
AB  - Gastrointestinal parasites, protozoa and helminths, remain a common important
      finding in dogs presented to veterinary medical practices. Moreover, dogs may
      play an active role in the transmission of enteric parasites to humans, given
      their cohabitation, making canine gastrointestinal parasitism an issue of major
      concern for public health. To get an overview of the current state of canine
      gastrointestinal parasites' prevalence in Greece, a total of 1036 faecal samples
      were collected from dogs either presented in veterinary clinics or in animal
      shelters. Samples were examined by a combined sedimentation-flotation technique.
      Possible risk factors (age, ownership status, co-existence with other animals,
      coinfection with other parasites) were assessed using binary regression models
      for each one of the most prevalent parasites. The overall gastrointestinal
      parasite prevalence in dogs' faecal samples was 39%. A total of 11 intestinal
      parasitic species were detected and up to five different parasites were isolated
      in the same faecal sample. Toxocara canis was the most prevalent parasite in the
      studied population, followed by Isospora spp., Giardia spp., Uncinaria spp.,
      Trichuris vulpis, Ancylostoma spp., Toxascaris leonina, and Dipylidium caninum.
      Additionally, other genera (Taenia, Capillaria and Angiostrongylus) were also
      detected in very low percentages. Young, stray, living without other dogs,
      coinfected with T. vulpis or T. canis and free of Isospora spp. dogs were more
      likely to be infected by Giardia spp. Likewise, young, stray, coinfected with T.
      vulpis or T. canis but free of Giardia spp. dogs were more likely to be infected
      by Isospora spp. T. canis infections were more common in dogs coinfected with
      Isospora spp., Giardia spp., D. caninum, Tauaenia spp., T. vulpis and T. leonina
      Finally, T. vulpis more often infected older dogs and dogs coinfected with
      Isospora spp., Giardia spp. and T. canis Consequently, the prevalence of
      parasitized dogs was high and the diversity of parasites found was notable, which
      calls for a greater awareness among veterinarians and pet owners. The proposed
      prediction models should be taken under consideration in diagnostic approach of
      clinical cases, as well as in planning sustainable antiparasitic strategies.

PMID- 29173543
TI  - Canine visceral leishmaniasis follow-up: a new anti-IgG serological test more
      sensitive than ITS-1 conventional PCR.
AB  - Visceral leishmaniasis (VL) is a neglected tropical disease with dogs serving as
      reservoirs for one of its etiological agents, Leishmania infantum. In Brazil, VL
      control involves culling of seropositive dogs, among other actions. However, the
      most employed serological tests lack accuracy, and are not able to detect canine
      visceral leishmaniasis (CVL) during the early stages of infection. Early
      detection of CVL is highly desirable in order to shorten the contact time between
      the infected reservoirs and the vectors. In this study, we investigated the
      ability of two multiepitope proteins, PQ10 and PQ20, to detect CVL at earlier
      stages than currently employed methods, including ITS-1 conventional PCR. Using
      serum samples from naturally infected dogs, we observed that ELISA-PQ10 and ELISA
      PQ20 were able to detect Leishmania infection at earlier time points as compared
      with kDNA PCR-RFLP in anti-IgG and anti-IgM assays. Using sera from
      experimentally infected dogs, we monitored seroconversion using multiepitope
      proteins, ELISA-crude antigen, as well as ITS-1 conventional and real-time PCR.
      While seroconversion was detected by ELISA-crude antigen in 16.6% of the dogs,
      multiepitope proteins were able to detect seroconversion in more than 80% of
      them. Moreover, the ability of ELISA-PQ10 and ELISA-PQ20 to detect Leishmania
      infection at earlier time points as compared with conventional PCR was also
      confirmed in experimental infection dogs' sera. Immunofluorescence to Babesia
      canis and Ehrlichia canis did not show cross-reactions with ELISA-PQ10/PQ20
      positive samples. Results of real-time PCR and ELISA with multiepitope proteins
      were very similar, with concordances between 80 and 100%. Furthermore, our
      findings indicated that PQ10 and PQ20 immunoassays can be related to parasite
      load. ELISA-PQ10 and ELISA-PQ20 are more sensitive diagnostic tools for early CVL
      detection as compared with other methods They could potentially be used in
      screening tests due to easy execution and low costs facilities.

PMID- 29173544
TI  - Zoonotic and host-adapted genotypes of Cryptosporidium spp., Giardia duodenalis
      and Enterocytozoon bieneusi in dairy cattle in Hebei and Tianjin, China.
AB  - A total of 1040 fecal samples, collected from 12 dairy cattle farms in Hebei and
      Tianjin, near the Bohai area of China, were screened for Cryptosporidium spp.,
      Giardia duodenalis and Enterocytozoon bieneusi by polymerase chain reaction. The
      overall prevalence for Cryptosporidium, G. duodenalis and E. bieneusi was 1.0%
      (n=10), 4.7% (n=49) and 19.4% (n=202), respectively. Ten Cryptosporidium-positive
      samples were identified as C. parvum by DNA sequence analysis of the small
      subunit rRNA (SSU rRNA) gene. DNA sequencing of the 60-kDa glycoprotein gene
      revealed that the C. parvum samples were all subtype IIdA19G1. Forty-nine G.
      duodenalis-positive samples belonged to assemblage E (n=47) and assemblage E
      mixed with A (n=2), based on the sequenced SSU rRNA, triosephosphate isomerase,
      and glutamate dehydrogenase genes. Sequence analysis of the internal transcribed
      spacer (ITS) gene identified six known E. bieneusi genotypes, I (n=87), J (n=83),
      BEB4 (n=18), BEB6 (n=3), N (n=1) and Ebpc (n=1), along with three new genotypes,
      CHC6 (n=1), CHC7 (n=1) and CHC8 (n=7). Phylogenetic analysis showed that Ebpc
      belonged to zoonotic group 1, whereas the other E. bieneusi genotypes clustered
      within group 2. More studies are needed to better understand the species
      distributions and public health significance of these pathogens in the study
      areas.

PMID- 29173545
TI  - Anthelminthic activity of methanol extracts of Diospyros anisandra and Petiveria
      alliacea on cyathostomin (Nematoda: Cyathostominae) larval development and egg
      hatching.
AB  - Methanol extracts of plant structures are promising alternatives to traditional
      pharmaceutical anthelminthic treatments. An in vitro evaluation was done of how
      methanol extracts of Diospyros anisandra bark and leaves, and Petiveria alliacea
      stems and leaves, collected during the rainy and dry seasons, effected
      cyathostomin larval development and egg hatching. Seven concentrations (600, 300,
      150, 75, 37.5, 18.7 and 9.3MUg/ml) were tested using the egg hatch assay. An
      ANOVA was applied to identify differences between the concentrations and the
      controls. Fifty percent lethal concentration (LC50) and the 95% confidence
      interval were calculated with a probit analysis. At and above 37.5MUg/ml, the D.
      anisandra bark extracts from both seasons exhibited >=95% egg hatch inhibition
      (EHI), while the D. anisandra leaf extracts had >90% EHI at and above 75MUg/ml.
      For P. alliacea, the extracts from leaves and stems from either season exhibited
      >97% EHI at and above 300MUg/ml, although similar efficacy was also observed at
      lower concentrations with the rainy season stems (75MUg/ml) and leaves
      (150MUg/ml). Values for LC50 were lowest for the rainy season D. anisandra bark
      (10.2MUg/ml) and leaf extracts (18.4MUg/ml), followed by the rainy season P.
      alliacea stems extract (28.2MUg/ml). In the D. anisandra extracts, EHI was
      largely due to its ovicidal activity (>=96% beginning at 37.5MUg/ml), whereas in
      the P. alliacea extracts it was due to L1 larval hatch failure (>=90% beginning
      at 75MUg/ml). Overall, the rainy season D. anisandra bark extracts had a strong
      in vitro anthelminthic effect against cyathostomins by inhibiting larval
      development, and the rainy season P. alliacea stem extracts had a strong effect
      by preventing egg hatching. Both are possible control alternatives for these
      nematodes.

PMID- 29173546
TI  - Season-long control of flea and tick infestations in a population of cats in the
      Aeolian archipelago using a collar containing 10% imidacloprid and 4.5%
      flumethrin.
AB  - Cats that have outdoor access are highly exposed to ticks, fleas, mites and
      flying insects, though the risk to become infested by arthropods is less
      perceived in cats than in dogs. This has resulted in fewer treatment and
      prevention options being available for cats than for dogs. A collar containing a
      combination of 10% imidacloprid and 4.5% flumethrin (Seresto(r), Bayer Animal
      Health) is available for cats and licensed with claims against ticks and fleas
      for 7-8 months. Following the assessment of the efficacy of the collar against
      Leishmania infantum infection in privately owned cats living in the Aeolian
      archipelago, herein we report the efficacy of the collar in the treatment and
      prevention of tick and flea infestations in the same population of cats over a
      period of one year of observation. At the inclusion day (Study Day 0, SD 0), cats
      were visited and examined for ectoparasites (i.e., flea combing and tick thumb
      counts) and allocated to group 1 (G1; n=104; cats treated with Seresto(r) collar)
      or group 2 (G2; n=100; untreated controls) and further checked at SDs 210, 270
      and 360 (study closure). At SD 0, G1 and G2 had a comparable percentage of cats
      infested by fleas (45.2% and 49.0%; chi2=0.164; P=0.6859) and ticks (6.7% and
      14.0%; chi2=2.946; P=0.0861). The number of cats infested by fleas was reduced in
      G1, being 8.3%, 0% and 3.8% on SDs 210, 270 and 360, respectively, resulting in
      efficacies against fleas of 79.4%, 100% and 93.6% on SDs 210, 270 and 360. None
      of the cats in G1 was found infested by ticks after the application of the
      collar, whereas in G2 ticks were observed on 15.7%, 4.8%, 17.5% of the cats at
      the different follow up visits, leading to an overall efficacy against ticks of
      100%. A total of 375 ectoparasites were collected from cats, being 249 fleas (six
      Ctenocephalides canis, 240 Ctenocephalides felis and three Nosopsyllus fasciatus)
      and 126 ticks (87 Ixodes ventalloi and 39 Rhipicephalus pusillus). Field data
      gathered herein confirm a high efficacy of the collar in the prevention of tick
      and flea infestations on cats. This is of great importance both for the primary
      role of fleas and ticks as blood feeding parasites and, more importantly, because
      of their role as vectors of pathogens causing diseases of veterinary and medical
      importance.

PMID- 29173547
TI  - Bobcats (Lynx rufus) are natural definitive host of Besnoitia darlingi.
AB  - Bovine besnoitiosis, caused by Besnoitia besnoiti, is an economically important
      disease of cattle in many countries but its transmission remains a mystery. Wild
      felids are suspected to be its definitive hosts. The domestic cat (Felis catus)
      is known experimental definitive host for Besnoitia species of rodents. Here, we
      report for Besnoitia darlingi the first identification of a natural definitive
      host, the bobcat (Lynx rufus). Oocysts resembling Toxoplasma gondii
      (unsporulated; 10.9+/-0.8*12.1+/-0.2MUm; n=5) were detected microscopically in
      the feces of two of 25 free ranging wild bobcats from Mississippi, USA. After
      detailed investigation, we identified these oocysts as B. darlingi and not T.
      gondii. The IFN-gamma gene knockout (KO) mice fed oocysts from bobcats died of
      acute besnoitiosis and tachyzoites were found in their tissues. Oocysts were also
      mildly pathogenic to outbred Swiss Webster mice (SW) (Mus musculus). The SW mice
      fed oocysts became ill but generally survived and developed characteristic thick
      walled Besnoitia tissue cysts in their tongue and heart muscles and brains. Two
      laboratory-raised domestic cats (Felis catus) excreted B. darlingi oocysts after
      ingesting murine tissues infected with bobcat-derived oocysts. The parasite was
      successfully cultivated in African green monkey kidney fibroblast cells (CV-1
      cell line) seeded with infected murine tissue homogenate. The multilocus PCR-DNA
      sequencing (18S rDNA, 28S rDNA, and ITS-1) from culture-derived tachyzoites
      confirmed the parasite as B. darlingi. Our results suggest that bobcats may be an
      important link in the sylvatic cycle of Besnoitia species and bioassay or
      molecular tests are needed to differentiate Toxoplasma gondii-like oocysts in
      feces of felids, both domestic and wild cats.

PMID- 29173548
TI  - Haemonchus contortus beta-tubulin isotype 1 gene F200Y and F167Y SNPs are both
      selected by ivermectin and oxfendazole treatments with differing impacts on
      anthelmintic resistance.
AB  - Parasitism by Haemonchus contortus is one of the main limiting factors in small
      ruminant production in tropical areas. Benzimidazoles (BZ) and macrocyclic
      lactones (ML) are the most used anthelmintic classes in gastrointestinal
      nematodes control. There is considerable scientific evidence of a possible
      relation between the anthelmintic resistance to BZ and ML. This study aimed to
      characterize the dynamics of anthelmintic resistance in an H. contortus
      susceptible isolate under selection pressure for BZ and ML alone or in
      combination and the role of isotype 1 beta-tubulin gene SNPs in these situations.
      A total of 12 Somali sheep were infected with 5000 third stage larvae of H.
      contortus Inbred-Susceptible Edinburgh (ISE) isolate. Once infection was
      established, animals were distributed in three groups (n=4), each treated with
      crescent doses of oxfendazole (OXF), ivermectin (IVM) and oxfendazole plus
      ivermectin (IVMOXF). An additional control group with untreated animals was
      maintained during the entire experiment. After each treatment, eggs were
      collected and real-time PCR was performed to identify single nucleotide
      polymorphisms (SNPs) F167Y, F200Y and E198A, in addition to egg hatch test (EHT)
      for BZ and larval development test (LDT) for ivermectin resistance. All
      treatments led to increased resistance allelic frequencies at SNPs F200Y and
      F167Y (p <0.05). In vitro results showed increased phenotypic resistance against
      both anthelmintic classes in groups IVM and IVMOXF while group OXF only developed
      resistance against BZ. Finally, we provide evidence that while isotype 1 beta
      tubulin gene SNPs may have some involvement with ML resistance, the presence of
      these beta-tubulin SNPs alone are not sufficient to develop ML resistance.

PMID- 29173549
TI  - A Layered Anatomic Description of the Anterolateral Complex of the Knee.
AB  - Variability in anatomic terminology, dissection protocols, and use of embalmed as
      opposed to fresh frozen specimens has led to the controversy surrounding the
      "anterolateral ligament of the knee." Conceptually the complex anatomy of the
      anterolateral knee is made up of the superficial, middle, deep, and capsulo
      osseous layers of the iliotibial band. The anterolateral capsule is deep to these
      tissues and is directly attached to the lateral meniscus. These structures
      collectively form the anterolateral complex of the knee. The anterolateral
      complex in conjunction with the anterior cruciate ligament function to prevent
      anterolateral rotatory instability of the knee.

PMID- 29173550
TI  - The Role of an Extra-Articular Tenodesis in Revision of Anterior Cruciate
      Ligament Reconstruction.
AB  - Patients who present for anterior cruciate ligament (ACL) revision with a high
      grade pivot shift at the time of an index ACL revision procedure and subsequent
      reconstruction failure or a high-grade pivot shift at revision surgery, patients
      with generalized joint laxity, and those requiring softs tissue grafts should be
      considered candidates for lateral tenodesis to supplement intraarticular graft
      revision. Although there is no consensus regarding the optimal lateral tenodesis
      technique, due to the tibial positioning associated with tensioning and fixation
      of extra-articular procedures, a lateral tenodesis should not be used in patients
      with posterolateral corner injuries or lateral compartment articular disease.

PMID- 29173551
TI  - Extra-Articular Plasty for Revision Anterior Cruciate Ligament Reconstruction.
AB  - Recent studies have renewed interest in the structures of the anterolateral
      aspect of the knee. Concomitant damage to these structures in the setting of
      anterior cruciate ligament rupture has led to various surgical techniques to
      address these combined injuries. This article is a description of the rationale
      and the indications for lateral extra-articular tenodesis as well as surgical
      technique.

PMID- 29173552
TI  - The Influence of Tibial and Femoral Bone Morphology on Knee Kinematics in the
      Anterior Cruciate Ligament Injured Knee.
AB  - Bone morphology is one feature that contributes to knee kinematics. The geometry
      of the tibia and femur vary across individuals, and these differences can
      influence the risk of anterior cruciate ligament (ACL) injury and of failure
      after isolated ACL reconstruction. There has been renewed interest in lateral
      extra-articular stabilization procedures to supplement an ACL reconstruction,
      although which patients benefit most from these procedures remains unclear. This
      article reviews the impact of bone morphology on knee kinematics, including
      tibial slope, depth of the medial tibial plateau, intercondylar notch shape,
      tibial eminence volume, and sphericity of the femoral condyles.

PMID- 29173553
TI  - What Is the State of the Evidence in Anterolateral Ligament Research?
AB  - The anterolateral ligament (ALL) is a capsular structure of the knee that is the
      subject of increasing academic interest. This article reviewed recent ALL
      literature in terms of subject matter and quality. Although current literature
      focusing on the ALL is small and limited to level 4 and 5 evidence, it is rapidly
      expanding. Cadaveric studies describing ALL biomechanics are the most common
      study design, followed by radiographic studies. The methodologic quality of
      cadaveric studies focusing on the ALL is high. Clinically oriented research
      pertaining to the diagnosis, therapy, prevalence, or prognosis of injury to the
      ALL is presently lacking.

PMID- 29173554
TI  - Biomechanics of the Anterolateral Structures of the Knee.
AB  - This article describes the complex anatomic structures that pass across the
      lateral aspect of the knee, particularly the iliotibial tract and the underlying
      anterolateral ligament and capsule. It provides data on their strength and roles
      in controlling tibiofemoral joint laxity and stability. These findings are
      discussed in relation to surgery to repair or reconstruct the anatomic
      structures, or to create tenodeses with similar effect.

PMID- 29173555
TI  - Biomechanical Proof for the Existence of the Anterolateral Ligament.
AB  - With the recent "description" of the anterolateral ligament (ALL) of the knee,
      its role in controlling rotational stability has reemerged. An improved
      understanding of the anatomy of the anterolateral complex of the knee has led to
      an expansion of the literature on the biomechanics of many structures, including
      the contribution of the iliotibial band and its deep (Kaplan) fibers, the capsulo
      osseous layer, the ALL, and the lateral meniscal posterior root to knee
      stability. This article describes the primary and secondary roles of key anatomic
      structures at the anterolateral aspect of the knee.

PMID- 29173556
TI  - Structural Properties of the Anterolateral Complex and Their Clinical
      Implications.
AB  - The role of the anterolateral complex of the knee in providing static and
      rotatory knee stability has been a source of renewed interest in the literature.
      Several studies have established a role of the anterolateral complex in
      controlling knee rotational stability. Although the objective quantification of
      knee kinematics and stability has been investigated, understanding of the
      structural properties of the anterolateral complex is evolving. This article
      highlights recent evidence pertaining to the structural properties of the
      anterolateral structures. The biomechanical evaluation of the structural
      properties of the anterolateral complex of the knee yielded minimal involvement
      in controlling knee rotational stability.

PMID- 29173557
TI  - Secondary Stabilizers of Tibial Rotation in the Intact and Anterior Cruciate
      Ligament Deficient Knee.
AB  - The controversy regarding the existence and function of the anterolateral
      ligament or anterolateral complex has reinvigorated interest in rotational
      stability of the knee joint. This is particularly true of anterolateral rotary
      instability, as many patients, despite anatomic reconstruction of their anterior
      cruciate ligament, continue to experience instability. Many experts point toward
      compromised anterolateral restraints as the underlying culprit, namely, the
      anterolateral complex, which includes the iliotibial band, anterolateral capsule,
      lateral meniscus, and lateral collateral ligament. This article provides a
      breakdown of these structures, their function, biomechanical properties, and
      clinical importance, based on a thorough review of available literature.

PMID- 29173558
TI  - Do We Need Extra-Articular Reconstructive Surgery?
AB  - With renewed interest in the lateral soft tissue envelope anatomy, there is also
      a rise in the popularity of extra-articular anterolateral procedures. There is
      reasonable laboratory-based evidence for additional benefit of such procedures,
      but clinical data are not sufficient to judge outcome in the long term for better
      or worse. Furthermore, the decision-making process to decide when to add an extra
      articular procedure is lacking; there are no clinical tests or investigations to
      guide the clinician. This article presents an overview of the literature and
      reflections from the authors on the subject.

PMID- 29173559
TI  - Anterolateral Ligament Reconstruction or Extra-Articular Tenodesis: Why and When?
AB  - Residual rotational laxity following anterior cruciate ligament (ACL)
      reconstruction has been identified as significant concern in many patients,
      despite evolution of techniques. The expanding body of knowledge on the anatomy
      and biomechanics of the anterolateral soft tissue restraints in rotational
      control of the knee has reignited an interest in extra-articular reconstruction
      techniques for augmenting ACL reconstruction. Reconstruction techniques currently
      used can be broadly categorized as either lateral extra-articular tenodesis or
      reconstruction of the anterolateral ligament. In this article, we outline the
      relevant anatomy, biomechanics, and rationale behind the indications and
      technique of our current extra-articular augmentation procedure.

PMID- 29173560
TI  - Extra-Articular Tenodesis in Combination with Anterior Cruciate Ligament
      Reconstruction: An Overview.
AB  - Anterior cruciate ligament (ACL) reconstruction is a successful procedure with
      high rates of return to sport. However, some patients experience persistent
      instability and graft failure. These adverse events have a significant impact,
      especially on high-level athletes. In an effort to improve outcomes for these
      patients, more attention is being paid to the anatomic structures at the
      anterolateral aspect of the knee. The anterolateral structures of the knee have
      been shown to play a major role in decreasing rotatory knee instability and
      forces across the ACL graft following reconstruction. This article discusses the
      indications and techniques for anterolateral ligament reconstruction or lateral
      extra-articular tenodesis, along with the newest anatomic and biomechanics
      concepts.

PMID- 29173561
TI  - The Anterolateral Ligament Does Exist: An Anatomic Description.
AB  - The debate around the existence, anatomy, and role of the so-called anterolateral
      ligament of the knee represents one of the main sources of recent controversy
      among orthopedic surgeons. In the modern era of sports medicine, several content
      experts have contributed to the understanding of the anatomy of the anterolateral
      aspect of the knee. This article analyzes the historical, phylogenetic, anatomic,
      arthroscopic, and radiological evidence regarding the anterolateral ligament. The
      existence of the anterolateral ligament as a distinct ligamentous structure and
      its exact anatomic features are still matters of controversy and ongoing study.

PMID- 29173562
TI  - Erratum.

PMID- 29173563
TI  - ALL or None?

PMID- 29173565
TI  - ?

PMID- 29173564
TI  - Structures of the Anterolateral Knee: Why All the Confusion?

PMID- 29173566
TI  - [Adolescent writing, becoming the narrator of one's own life].
AB  - Mediation through writing is a valuable tool to be used as a means of
      symbolisation in the period of psychological and physical tensions common to
      adolescence. By creating their own space in which to create, the evolving written
      account enables young people to think about their psychological life by
      considering the place of each individual. Each clue in the writing is to be
      understood in relation to the way the adolescent functions psychologically.

PMID- 29173567
TI  - [Initiating psychiatric care for young, isolated foreigners].
AB  - The various traumatic events experienced by young isolated foreigners can weaken
      them psychologically and cause psychiatric decompensation. A qualitative study,
      carried out by the Maison de Solenn and the Avicenne hospital, aimed to provide
      better understanding of the conditions for initiating psychiatric care with these
      adolescents. The different results show that this type of care for these young
      migrants must be cross-cultural and multi-disciplinary.

PMID- 29173568
TI  - [Support group for hospitalised adolescents: support for growing up].
AB  - The theme of growing up is addressed through the presentation of the support
      group for around twenty hospitalised adolescents at the Maison de Solenn. In this
      weekly group, the subjects discussed are diverse in terms of their content and
      tone, depending on the atmosphere or changes: sharing daily life in hospital, the
      tastes and ideas of each participant, issues related to adolescence, to topics
      bordering on the philosophical or existential. The analysis of the themes
      discussed over the course of a year revealed that many provide the basis for
      thinking about the process of separation/individuation.

PMID- 29173569
TI  - [Different perspectives of educational systems with a cross-cultural assessment].
AB  - In the framework of cross-cultural assessments, the nursing team is instructed by
      the family court judge to provide a clinical assessment taking into account the
      cultural dimension of the young person concerned. The aim is also to define
      appropriate psychoeducational support for certain migrant families, notably those
      describing a brutal confrontation between the educational worlds of here and
      elsewhere. The situation of a Togolese family, whose adolescent daughter is taken
      into care due to a practice judged to be abuse in France, is analysed in order to
      provide some keys to understanding and to discuss the anthropological aspects
      relevant to the educational and psychological care.

PMID- 29173570
TI  - [Refusal of care by a HIV-positive adolescent: role of the cross-cultural
      approach].
AB  - The refusal of treatment is frequent in human immunodeficiency virus-positive
      adolescents. The clinical history of a teenage girl presenting severe
      immunodepression secondary to the virus, a depressive disorder and a refusal of
      treatment, illustrates the benefit of combined paediatric, child psychiatric and
      cross-cultural care as proposed by the Cochin-Paris Adolescent Centre. Working on
      the meaning of the refusal was a prerequisite for the construction of a care
      project forming part of a life project, as the psychopathological work could only
      begin once somatic care ensuring the patient's protection was in place.

PMID- 29173571
TI  - [Adolescents at play: the benefit of individual psychoanalytic psychodrama].
AB  - An individual psychoanalytic psychodrama session with an adolescent treated at
      the Maison de Solenn shows the benefit of psychodrama role playing. Using the
      body, the imagination and 'pretend play', this therapy gives access to
      symbolisation and facilitates the care process.

PMID- 29173572
TI  - [When the psychotic person is an alcoholic: working on acceptance].
AB  - Alcohol dependence in a person with psychosis is a complex question.
      Paradoxically, by trying to stay alive, the person places themselves in serious
      danger, without consideration for their body or their life. Withdrawal could have
      worse effects than the continuation of alcohol use. The support within a French
      service for the medical-social support of mentally disabled adults (SAMSAH)
      therefore involves going not towards the change that we want for the person, but
      towards acceptance of what they are, in order to open up the future.

PMID- 29173573
TI  - [A global approach to therapeutic education for patients with schizophrenia].
AB  - Thanks to the wealth of multiple competencies, it is now possible to undertake a
      global approach with the patient with schizophrenia based on therapeutic
      education. An 'a la carte' evolutive programme can respond to the issues inherent
      to this disorder, on condition that the caregivers have developed a common
      culture and values. An example of a programme implemented in La Chartreuse
      hospital in Dijon.

PMID- 29173574
TI  - ?

PMID- 29173575
TI  - ?

PMID- 29173576
TI  - Preterm delivery trends by maternal race/ethnicity in the United States, 2006
      2012.
AB  - PURPOSE: To estimate changes in preterm delivery (PTD) in the United States from
      2006 to 2012 by clinical circumstance, timing of delivery, and race/ethnicity.
      METHODS: We used vital statistics natality data on all singleton live births from
      the 18 U.S. states continuously using the 2003 birth certificate from 2006 to
      2012. We estimated change in PTD overall and by clinical circumstance
      (spontaneous vs. medically indicated) and delivery timing among all women and by
      race/ethnicity, using descriptive and multivariable regression methods. RESULTS:
      Overall, indicated, and spontaneous PTD declined by 10.31%, 8.40%, and 11.52%,
      respectively. Late-preterm, early-term, and post-term deliveries decreased
      substantially (12.13%, 18.37%, and 32.20%, respectively), with simultaneous
      increase (13.57%) in full-term deliveries. Non-Hispanic white, non-Hispanic
      black, and Asian/Pacific Islander women experienced larger declines in PTD
      compared with Hispanic and American Indian/Alaska Native women. Non-Hispanic
      white women experienced larger declines in late and medically indicated PTD,
      while non-Hispanic black women experienced larger declines in early and moderate
      and spontaneous PTD. CONCLUSIONS: Overall, spontaneous, and indicated PTD
      declined from 2006 to 2012. Declines were lower than previously reported and
      differed substantially by race/ethnicity.

PMID- 29173577
TI  - Body mass index trajectories during infancy and pediatric obesity at 6 years.
AB  - PURPOSE: The purpose of the article was to examine the relationship between body
      mass index (BMI) trajectories during infancy and risk of obesity at the age of 6
      years. METHODS: We used data on 1169 children with at least two BMI measures
      during their first year of life from the Infant Feeding Practices Survey II and
      its Year 6 Follow-Up. Latent class growth analysis was used to identify distinct
      trajectories of BMI, and multiple logistic regression analyses were used to
      assess the association of the identified trajectories with obesity at the age of
      6 years. RESULTS: Three trajectories of BMI were identified during the first year
      of life: low stable (80.2%), high stable (16.9%), and rising (2.8%). Obesity at
      the age of 6 years was highest among children with a high-stable trajectory
      (17.2%), followed by the low-stable (9.6%) and rising (9.1%) groups. Compared
      with those in the low-stable trajectory, the adjusted odds ratio for obesity at
      the age of 6 years was 1.79 (95% confidence interval 1.13-2.84) in children with
      the high-stable growth trajectory and 0.84 (0.26-2.72) in children with the
      rising growth trajectory. CONCLUSIONS: High-stable BMI trajectory in infancy
      resulted in a higher risk for obesity at the age of 6 years, but had low accuracy
      for identifying obese children at the age of 6 years.

PMID- 29173578
TI  - Examining racial disparities in colon cancer clinical delay in the Colon Cancer
      Patterns of Care in Chicago study.
AB  - PURPOSE: We explored a potential racial disparity in clinical delay among non
      Hispanic (nH) Black and White colon cancer patients and examined factors that
      might account for the observed disparity. METHODS: Patients aged 30-79 years with
      a newly diagnosed colon cancer from 2010 to 2014 (n = 386) were recruited from a
      diverse sample of nine public, private, and academic hospitals in and around
      Chicago. Prolonged clinical delay was defined as 60 days or more or 90 days or
      more between medical presentation (symptoms or a screen-detected lesion) and
      treatment initiation (surgery or chemotherapy). Multivariable logistic regression
      with model-based standardization was used to estimate the disparity as a
      difference in prevalence of prolonged delay by race. RESULTS: Prevalence of delay
      in excess of 60 days was 12 percentage points (95% confidence interval: 2%, 22%)
      higher among nH Blacks versus Whites after adjusting for age, facility, and
      county of residence. Travel burden (time and distance traveled from residence to
      facility) explained roughly one-third of the disparity (33%, P = .05), individual
      and area-level socioeconomic status measures explained roughly one-half (51%, P =
      .21), and socioeconomic measures together with travel burden explained roughly
      four-fifths (79%, P = .08). CONCLUSIONS: Low socioeconomic status and increased
      travel burden are barriers to care disproportionately experienced by nH Black
      colon cancer patients.

PMID- 29173579
TI  - Contextual effects and cancer outcomes in the United States: a systematic review
      of characteristics in multilevel analyses.
AB  - PURPOSE: There is increasing call for the utilization of multilevel modeling to
      explore the relationship between place-based contextual effects and cancer
      outcomes in the United States. To gain a better understanding of how contextual
      factors are being considered, we performed a systematic review. METHODS: We
      reviewed studies published between January 1, 2002 and December 31, 2016 and
      assessed the following attributes: (1) contextual considerations such as
      geographic scale and contextual factors used; (2) methods used to quantify
      contextual factors; and (3) cancer type and outcomes. We searched PubMed, Scopus,
      and Web of Science and initially identified 1060 studies. One hundred twenty-two
      studies remained after exclusions. RESULTS: Most studies utilized a two-level
      structure; census tracts were the most commonly used geographic scale.
      Socioeconomic factors, health care access, racial/ethnic factors, and rural-urban
      status were the most common contextual factors addressed in multilevel models.
      Breast and colorectal cancers were the most common cancer types, and screening
      and staging were the most common outcomes assessed in these studies. CONCLUSIONS:
      Opportunities for future research include deriving contextual factors using more
      rigorous approaches, considering cross-classified structures and cross-level
      interactions, and using multilevel modeling to explore understudied cancers and
      outcomes.

PMID- 29173580
TI  - Building the pipeline: programs to introduce middle school, high school, medical,
      and veterinary students to careers in epidemiology and public health.
AB  - PURPOSE: This report describes Centers for Disease Control and Prevention
      programs that expose students to epidemiology and public health sciences (EPHS).
      METHODS: The Science Ambassador workshop targets middle and high school teachers
      and promotes teaching EPHS in the classroom. The National Science Olympiad
      Disease Detectives event is an extracurricular science competition for middle and
      high school students based on investigations of outbreaks and other public health
      problems. The Epidemiology Elective Program provides experiential learning
      activities for veterinary and medical students. RESULTS: As of 2016, 234 teachers
      from 37 states and territories and three other countries participated in SA
      workshops. Several are teaching units or entire courses in EPHS. The National
      Science Olympiad Disease Detectives event exposed approximately 15,000 middle and
      high school students to EPHS during the 2015-2016 school year. The Epidemiology
      Elective Program has exposed 1,795 veterinary and medical students to EPHS.
      CONCLUSIONS: Students can master fundamental concepts of EPHS as early as middle
      school and educators are finding ways to introduce this material into their
      classrooms. Programs to introduce veterinary and medical students to EPHS can
      help fill the gap in exposing older students to the field. Professional
      organizations can assist by making their members aware of these programs.

PMID- 29173581
TI  - SUB-GROUPS? BEAR WITH ME!

PMID- 29173582
TI  - Staphylococcus agnetis, a potential pathogen in broiler breeders.
AB  - In this study, four broiler parent flocks have been followed from the onset of
      the production period (week 20) until slaughter (week 60). Every week,
      approximately ten dead broiler breeders, randomly selected among birds dead on
      their own, were collected and subjected to a full post mortem analysis including
      bacteriological examination. In total 997 breeders were investigated and for the
      first time Staphylococcus agnetis was isolated in pure culture from cases of
      endocarditis and septicemia from 16 broiler breeders. In addition, the cloacal
      flora from newly hatched chickens originating from the same four flocks were
      characterized and S. agnetis was found in pure culture of several newly hatched
      chickens (n=12) and only in one case in combination with another species.
      Clonality of the isolates was examined by pulsed-field-gel-electrophoresis which
      showed indistinguishable patterns in isolates from both broiler breeders and
      broilers. Three isolates were whole genome sequenced to obtain knowledge on
      virulence genes. The isolates harbored a number of genes encoding different
      fibrinogen binding proteins and toxins which might be important for virulence.
      The present findings demonstrate that S. agnetis may be associated with mortality
      in broiler breeders. No disease was associated with the broilers which were found
      positive for S. agnetis in the cloaca.

PMID- 29173583
TI  - Pathogenicity and transmissibility of a highly pathogenic avian influenza virus
      H5N6 isolated from a domestic goose in Southern China.
AB  - Since the first outbreak of H5N6 reported in Laos at 2013, there has been a
      dramatic increase in H5N6 strains isolated from waterfowl in China, particularly
      Southern China. However, pathogenicity and transmissibility of the virus in
      different birds remain largely unknown. In this study, a novel H5N6 virus, termed
      QY01, that belonged to group C in 2.3.4.4 was isolated from an apparently healthy
      domestic goose in Guangdong province, southern China in 2016. In order to
      simulate the natural transmission of different kinds of birds, we evaluated its
      pathogenicity and transmissibility in chickens, domestic geese and pigeons. To
      investigate the replication and shedding of QY01 in poultry, chickens, geese and
      pigeons were inoculated intranasally with 106 EID50 of virus. In addition, to
      measure intra-species transmission of QY01, three sentinel birds were housed with
      each group. The results demonstrated that QY01 exhibited a highly pathogenic
      phenotype, and was transmissible among in chickens and geese. However, the virus
      did not appear to be pathogenic in pigeons, indicating that this novel H5N6 virus
      exhibited different host ranges and tissue tropisms, and may pose a substantial
      risk for the chicken and goose industry. Therefore, continued surveillance for
      H5N6 AIVs is necessary, and increased attention should be paid to cross-species
      transmission between waterfowl and terrestrial birds.

PMID- 29173584
TI  - Candida parapsilosis complex in veterinary practice: A historical overview,
      biology, virulence attributes and antifungal susceptibility traits.
AB  - The Candida genus is composed by yeast that commensally live as part of human and
      animal microbiota. In the last years, C. parapsilosis complex, composed by the
      cryptic species C. parapsilosis sensu stricto, C. orthopsilosis and C.
      metapsilosis, has been frequently implicated in human nosocomial infections in
      Europe and Latin America. In veterinary medicine, C. parapsilosis sensu lato
      infections have been reported in different animal species. Several putative
      virulence factors have been associated with the pathogenicity of this species
      complex, including biofilm formation and the production of proteases,
      phospholipases, lipases and other hydrolytic enzymes. Additionally, these species
      have developed antifungal resistance, especially to azole derivatives and
      echinocandins. Thus, considering the pathogenic potential of the C. parapsilosis
      species complex, along with the emergence of antifungal resistant strains, this
      review was designed to approach historical and biological aspects,
      microbiological features, virulence factors and antifungal susceptibility traits
      of C. parapsilosis complex from animals.

PMID- 29173585
TI  - European surveillance of emerging pathogens associated with canine infectious
      respiratory disease.
AB  - Canine infectious respiratory disease (CIRD) is a major cause of morbidity in
      dogs worldwide, and is associated with a number of new and emerging pathogens. In
      a large multi-centre European study the prevalences of four key emerging CIRD
      pathogens; canine respiratory coronavirus (CRCoV), canine pneumovirus (CnPnV),
      influenza A, and Mycoplasma cynos (M. cynos); were estimated, and risk factors
      for exposure, infection and clinical disease were investigated. CIRD affected 66%
      (381/572) of the dogs studied, including both pet and kennelled dogs. Disease
      occurrence and severity were significantly reduced in dogs vaccinated against
      classic CIRD agents, canine distemper virus (CDV), canine adenovirus 2 (CAV-2)
      and canine parainfluenza virus (CPIV), but substantial proportions (65.7%;
      201/306) of vaccinated dogs remained affected. CRCoV and CnPnV were highly
      prevalent across the different dog populations, with overall seropositivity and
      detection rates of 47% and 7.7% for CRCoV, and 41.7% and 23.4% for CnPnV,
      respectively, and their presence was associated with increased occurrence and
      severity of clinical disease. Antibodies to CRCoV had a protective effect against
      CRCoV infection and more severe clinical signs of CIRD but antibodies to CnPnV
      did not. Involvement of M. cynos and influenza A in CIRD was less apparent.
      Despite 45% of dogs being seropositive for M. cynos, only 0.9% were PCR positive
      for M. cynos. Only 2.7% of dogs were seropositive for Influenza A, and none were
      positive by PCR.

PMID- 29173586
TI  - Differential immune-related gene expression in the spleens of duck Tembusu virus
      infected goslings.
AB  - Flaviviruses pose a significant threat to public health worldwide. Recently, a
      novel flavivirus, duck Tembusu virus (TMUV), was identified as the causative
      agent of a serious duck viral disease in Asia. Its rapid spread and expanded host
      range have raised substantial concerns regarding its potential threat to non
      avian hosts, including humans. However, the specific molecular host responses to
      this virus are poorly understood. In this study, we used the RNA-sequencing
      technique to analyse the differential gene expression in the spleens of infected
      goslings 5days post-infection. In total, 2878 upregulated unigenes and 2943
      downregulated unigenes were identified. The Gene Ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed
      that different pattern recognition receptor (PRR) signalling pathways
      simultaneously participated in the sensing of the pathogen-associated molecular
      patterns (PAMPs) of TMUV, and the antigen presentation pathway and acquired
      immunity were activated. Then, the signals were transduced by the NF-kappa B (NF
      kappaB) or the Janus kinase/signal transducers and activators of transcription
      (JAK/STAT) pathways, resulting in the enormous production of various cytokines
      and interferon-stimulated genes (ISGs). We further investigated the immune
      response patterns in the liver and brain tissue using RT-qPCR. The bacterial
      peptidoglycan sensor nucleotide-binding oligomerization domain-containing protein
      1 (NOD1) receptor was significantly upregulated, especially in the brain tissue,
      suggesting that NOD1 likely induces an inflammatory response by interacting with
      dsRNA, which is similar to its actions during hepatitis C viral (HCV) infection.
      However, major histocompatibility complex II (MHCII) was downregulated only in
      the spleen, indicating that the downregulation of MHCII in the spleen may be an
      immune evasion strategy of TMUV to facilitate pathogenesis during infection.
      Here, we are the first to report a transcriptome analysis of the host immune
      response to TMUV infection, and the data reported herein may help elucidate the
      molecular mechanisms of the gosling-TMUV interaction.

PMID- 29173587
TI  - Interferon alpha inhibits replication of a live-attenuated porcine reproductive
      and respiratory syndrome virus vaccine preventing development of an adaptive
      immune response in swine.
AB  - Type I interferons, such as interferon alpha (IFN-alpha), contribute to innate
      antiviral immunity by promoting production of antiviral mediators and are also
      involved in promoting an adaptive immune response. Porcine reproductive and
      respiratory syndrome virus (PRRSV) is one of the most devastating and costly
      viruses to the swine industry world-wide and has been shown to induce a meager
      IFN-alpha response. Previously we administered porcine IFN-alpha using a
      replication-defective adenovirus vector (Ad5-IFN-alpha) at the time of challenge
      with virulent PRRSV and demonstrated an increase in the number of virus-specific
      IFNgamma secreting cells, indicating that the presence of IFN-alpha at the time
      of infection can alter the adaptive immune responses to PRRSV. In the current
      experiment, we explored the use of IFN-alpha as an adjuvant administered with
      live-attenuated PRRSV vaccine as a method to enhance immune response to the
      vaccine. Unlike the previous studies with fully virulent virus, one injection of
      the Ad5-IFN-alpha abolished replication of the vaccine virus and as a result
      there was no detectible adaptive immune response. Although IFN-alpha did not have
      the desired adjuvant effect, the results further highlight the use of IFN-alpha
      as a treatment for PRRSV infection.

PMID- 29173588
TI  - A comprehensive study of hepatitis E virus infection in pigs entering a
      slaughterhouse in Slovenia.
AB  - Hepatitis E is a zoonotic viral disease of pigs with increasing public health
      concern in industrialized countries. Presented broad study of hepatitis E virus
      (HEV) presence in pigs in Slovenia is the first attempt to overview the HEV
      situation in pigs entering a slaughterhouse and, further, to analyse the
      possibility of HEV entering into the food supply chain. 2433 samples from 811
      clinically healthy pigs were collected at four slaughterhouses in Slovenia.
      Sampling covered three different age groups of pigs and three different types of
      samples (faeces, bile and liver) important for tracing HEV in a pig population.
      In addition, 63 swab samples were collected systematically from three different
      sites on the slaughter line, as well as 22 samples of minced meat and 30
      bratwurst samples. All the samples were screened for the presence of HEV nucleic
      acids by specific real-time RT-PCR assay. In the group of three month old pigs
      13.7% of faeces, 13.0% of bile and 2.1% of liver samples were HEV positive. In
      the group of six months old pigs only 0.25% of liver and 0.25% of bile samples
      were positive. In the category of sows, no positive samples were found. Two out
      of 63 swab samples collected on the slaughter line were HEV positive. All tested
      samples of minced meat and bratwurst were negative. The phylogenetic analysis of
      50 HEV positive samples, with comparison of 366 nucleotides in ORF1 region,
      revealed high diversity of identified strains of HEV in pigs, belonging into
      subtypes 3a, 3b, 3c and 3e.

PMID- 29173589
TI  - EIF3i affects vesicular stomatitis virus growth by interacting with matrix
      protein.
AB  - The matrix protein of vesicular stomatitis virus (VSV) performs multiple
      functions during viral genome replication and virion production and is involved
      in modulating multiple host signaling pathways that favor virus replication. To
      perform numerous functions within infected cells, the M protein needs to recruit
      cellular partners. To better understand the role of M during VSV replication, we
      looked for interacting partners by using the two-hybrid system. The eukaryotic
      translation initiation factor 3, subunit i (eIF3i) was identified to be an M
      binding partner, and this interaction was validated by GST pull-down and laser
      confocal assays. Through a mutagenesis analysis, we found that some mutants of M
      between amino acids 122 and 181 impaired but did not completely abolish the M
      eIF3i interaction. Furthermore, the knockdown of eIF3i by RNA interference
      decreased viral replication and transcription in the early stages but led to
      increase in later stages. VSV transcription was increased at 4h post-infection
      but was not changed at 8 and 12h post-infection after the over-expression of
      eIF3i. Finally, we also demonstrated that VSV could inhibit the activity of Akt1
      and that the knockdown of eIF3i inhibited the expression of the ISGs regulated by
      phospho-Akt1. These results indicated that eIF3i may affect VSV growth by
      regulating the host antiviral response in HeLa cells.

PMID- 29173590
TI  - Gene expression profiling of chicken cecal tonsils and ileum following oral
      exposure to soluble and PLGA-encapsulated CpG ODN, and lysate of Campylobacter
      jejuni.
AB  - Campylobacter jejuni (C. jejuni) is a leading bacterial cause of food-borne
      illness in humans. Contaminated chicken meat is an important source of infection
      for humans. Chickens are not clinically affected by colonization, and immune
      responses following natural infection have limited effects on bacterial load in
      the gut. Induction of intestinal immune responses may possibly lead to a
      breakdown of the commensal relationship of chickens with Campylobacter. We have
      recently shown that soluble and poly D, L-lactic-co-glycolic acid (PLGA)
      encapsulated CpG oligodeoxynucleotide (ODN) as well as C. jejuni lysate, are
      effective in reducing the intestinal burden of C. jejuni in chickens; however,
      the mechanisms behind this protection have yet to be determined. The present
      study was undertaken to investigate the mechanisms of host responses conferred by
      these treatments. Chickens were treated orally with soluble CpG ODN, or PLGA
      encapsulated CpG ODN, or C. jejuni lysate, and expression of cytokines and
      antimicrobial peptides was evaluated in cecal tonsils and ileum using
      quantitative RT-PCR. Oral administration of soluble CpG ODN upregulated the
      expression of interferon (IFN)-gamma, interleukin (IL)-1beta, CXCLi2,
      transforming growth factor (TGF)-beta4/1, IL-10 and IL-13, while treatment with
      PLGA-encapsulated CpG ODN upregulated the expression of IL-1beta, CXCLi2, TGF
      beta4/1, IL-13, avian beta-defensin (AvBD) 1, AvBD2 and cathelicidin 3 (CATHL-3).
      C. jejuni lysate upregulated the expression of IFN-gamma, IL-1beta, TGF-beta4/1,
      IL-13, AvBD1, and CATHL-3. In conclusion, induction of cytokine and antimicrobial
      peptides expression in intestinal microenvironments may provide a means of
      reducing C. jejuni colonization in broiler chickens, a key step in reducing the
      incidence of campylobacteriosis in humans.

PMID- 29173591
TI  - Immunogenicity of a recombinant adenovirus expressing porcine reproductive and
      respiratory syndrome virus polyepitopes.
AB  - The objective of this work was to evaluate the immunogenicity of a chimeric
      antigen containing characterized PRRSV epitopes. A synthetic gene, designated
      HEJ, encoding defined epitopes was used to generate a recombinant adenovirus
      designed Ad-HEJ. The chimeric antigen included T-cell epitopes from structural
      and nonstructural proteins, and a neutralizing B-cell epitope. Following a
      homologous prime-boost immunization, the Ad-HEJ virus elicited significant
      (p<0.05) epitope-specific IFN-gamma responses compared to sham-treatment. Two
      weeks post-challenge, this response was significantly (p<0.05) higher compared to
      the negative control treatment. IFN-gamma response to PRRSV stimulation in vitro
      were observed in both groups only after challenge. Antibodies against PRRSV and
      peptides were detectable following prime-boost immunization in the Ad-HEJ
      treatment group and the responses increased post-challenge against the virus and
      against most of the peptides. All the swine were viremic one week post-challenge,
      but four weeks later, five out of the seven Ad-HEJ vaccinees had cleared the
      PRRSV, whereas only two of the six negative controls had cleared the virus. The
      outcome suggests that the adenovirus expressing defined epitopes induced a strong
      immune response against the peptides, but this response was not sufficient to
      confer protection against PRRSV challenge.

PMID- 29173592
TI  - West Nile virus in horses during the summer and autumn seasons of 2015 and 2016,
      Portugal.
AB  - West Nile fever (WNF) is an emergent disease in Europe, under surveillance in the
      European Union. Following a 5-year period of apparent silence (autumn 2010 to
      summer 2015), West Nile virus (WNV) reemerged in the South of Portugal, in July
      2015. Here we present data from the onset, geographic location within mainland
      Portugal, and outcome of clinical cases of WNV infection in horses in 2015 and
      2016. During the transmission seasons of 2015 and 2016, twenty-seven horses, most
      symptomatic (n=20) were found positive to IgM, pr-E immunoglobulins and VNT,
      leading to the subsequent report to Animal Disease Notification System of the
      European Commission (ADNS) by the Portuguese National Authority for Animal
      Health. Outbreaks occurred in the middle summer (August) and early/mid autumn
      (October/November) of 2015 and 2016, in the southern regions of the country
      (Alentejo and Algarve). Compared with the previous WNV transmission seasons of
      2004 and 2010, a higher number of cases were reported in 2015 and 2016. The
      results of our study contribute to increase information concerning the geographic
      areas affected and time period for WNV transmission risk in Portugal.

PMID- 29173593
TI  - Molecular and phylogenetic analyses of Salmonella Gallinarum trace the origin and
      diversification of recent outbreaks of fowl typhoid in poultry farms.
AB  - Fowl typhoid (FT) and pullorum disease (PD) are two important poultry infections
      caused by Salmonella enterica subsp. enterica serotype Gallinarum (S.
      Gallinarum). S. Gallinarum strains are adapted to birds and classified into
      biovars Gallinarum (bvGA) and Pullorum (bvPU) as they are the causative agent of
      FT and PD, respectively. In Brazil, FT/PD outbreaks have been reported along the
      last 50 years, but there was a recent increase of FT field reports with the
      suspicion it could be due to virulence reversion of the attenuated live vaccine
      SG9R. In this study, we applied molecular biology assays and phylogenetic methods
      to detect and investigate S. Gallinarum isolates from commercial poultry flocks
      in order to understand the evolutionary history and origin of the recent FT
      outbreaks in Brazil. S. Gallinarum isolates were obtained from thirteen different
      poultry flocks with clinical signs of FT/PD from 2013 to 2015. These isolates
      were serotyped, tested with three specific PCR (for the detection of bvGA, bvPU
      and live vaccine strain SG9R) and submitted to sequencing of a variable genome
      region (ISR analysis). The complete genome of one bvGA strain (BR_RS12) was also
      compared to other S. Gallinarum complete genomes (including other two Brazilian
      ones: bvGA 287/91 and bvPU FCVA198). PCR detected all thirteen isolates as S.
      Gallinarum (eight bvGA and five bvPU), none positive for SG9R strain. ISR
      analysis revealed that all eight bvGA isolates showed exactly the same nucleotide
      sequences with 100% similarity to reference strains, while two patterns were
      observed for bvPU. Genome phylogeny demonstrated distinct clades for bvGA and
      bvPU, with the bvGA clade showing a clear subdivision including three genomes:
      SG9R vaccine, the respective SG9 parent strain and one SG9R revertant field
      isolate (MB4523). The evolutionary rate of the total S. Gallinarum genome was
      calculated at 6.15*10-7 substitutions/site/year, with 2.8 observed substitutions
      per year per genome (1 SNP per 4292 bases). Phylodynamics analysis estimated that
      at least two introductions of S. Gallinarum bvGA happened in Brazil, the first in
      1885 and the second in 1950. The Brazilian bvGA genomes 287/91 and BR_RS12
      analyzed here were related to the early and the late introductions, respectively.
      In conclusion, these results indicate the occurrence of S. Gallinarum strains
      associated with FT outbreaks that have been circulating for more than 50 years in
      Brazil and are not originated from virulence reversion of the SG9R vaccine.

PMID- 29173594
TI  - Serological evidence of hepatitis E virus infection in zoo animals and
      identification of a rodent-borne strain in a Syrian brown bear.
AB  - Hepatitis E virus (HEV) is the causative agent of hepatitis E, an emerging
      infectious disease of humans. HEV infections have also been described in various
      animal species. Whereas domestic pigs and wild boars are well-known animal
      reservoirs for HEV, the knowledge on natural HEV infection in zoo animals is
      scarce so far. Here, we analysed 244 sera from 66 mammal species derived from
      three zoos in Germany using a commercial double antigen sandwich ELISA. HEV
      specific antibodies were detected in 16 animal species, with the highest
      detection rates in suids (33.3%) and carnivores (27.0%). However, RNA of the
      human pathogenic HEV genotypes 1-4 was not detected in the serum samples from
      suids or carnivores. Using a broad spectrum RT-PCR, a ratHEV-related sequence was
      identified in a sample of a female Syrian brown bear (Ursus arctos syriacus).
      Subsequent serum samples within a period of five years confirmed a HEV
      seroconversion in this animal. No symptoms of hepatitis were recorded. In a
      follow-up investigation at the same location, closely related ratHEV sequences
      were identified in free-living Norway rats (Rattus norvegicus), whereas feeder
      rats (Rattus norvegicus forma domestica) were negative for HEV-specific
      antibodies and RNA. Therefore, a spillover infection of ratHEV from free-living
      Norway rats is most likely. The results indicate that a wide range of zoo animals
      can be naturally infected with HEV or HEV-related viruses. Their distinct role as
      possible reservoir animals for HEV and sources of HEV infection for humans and
      other animals remains to be investigated.

PMID- 29173595
TI  - Do All Patients With Atrial Fibrillation Need a Cardiologist?

PMID- 29173596
TI  - The Placebo Effect in Cardiology: Understanding and Using It.
AB  - The placebo effect is the clinical benefit caused by interaction with a caregiver
      and health care system in the absence of a biologically active intervention and
      has been used successfully for millennia. The placebo response results from the
      interaction of psychosocial mechanisms, human relationships, and preconceptions
      functioning in specific neuroanatomic locations with known genes and
      neurotransmitters. It occurs with or without the administration of an inactive
      substance to deliberately deceive patients. Our purpose is to review the history,
      benefits, and mechanisms of the placebo effect. The placebo response results from
      classic conditioning and positive expectations about outcome expressed by the
      caregiver. The outcomes are usually symptoms such as pain rather than biological
      outcomes such as death, and the powerful placebo may account for more than half
      the effect of treatment in many situations. The placebo effect results from
      activation of opioid, cannabinoid, and dopaminergic pathways involved in reward,
      expectancy, conditioning, and pain modulation. Eleven specific anatomic features
      in the brain identified by positron emission tomography and magnetic resonance
      imaging are involved. Polymorphisms in the structural genes for catecholamine O
      methyltransferase and fatty acid amide oxidase significantly influence the
      placebo response. The placebo effect may be important in symptom suppression in
      angina, paroxysmal atrial fibrillation, and congestive heart failure. In the
      absence of deliberate deception, there are no ethical issues and given its
      potency, the time has come to consider how best to use the placebo in clinical
      practice.

PMID- 29173597
TI  - Congenital Heart Disease and Neurodevelopment: Clinical Manifestations, Genetics,
      Mechanisms, and Implications.
AB  - Children with congenital heart disease (CHD) are at increased risk of
      neurodevelopmental disorders (NDDs) and psychiatric conditions. These include
      cognitive, adaptive, motor, speech, behavioural, and executive functioning
      deficits, as well as autism spectrum disorder and psychiatric conditions.
      Structural and functional neuroimaging have demonstrated brain abnormalities in
      young children with CHD before undergoing surgical repair, likely as a result of
      an in utero developmental insult. Surgical factors do not seem to play a
      significant role in neurodevelopmental outcomes. Specific genetic abnormalities,
      particularly copy number variants, have been increasingly implicated in both CHD
      and NDDs. Variations in genes involved in apolipoprotein E (APOE) production, the
      Wnt signalling pathway, and histone modification, as well as in the 1q21.1,
      16p13.1-11, and 8p23.1 genetic loci, have been associated with CHD and NDDs and
      are important targets for future research. Understanding these associations is
      important for risk stratification, disease classification, improved screening,
      and pharmacologic management of individuals with CHD.

PMID- 29173598
TI  - Mechanisms, Clinical Significance, and Prevention of Cognitive Impairment in
      Patients With Atrial Fibrillation.
AB  - Atrial fibrillation (AF) and dementia are major health issues, with growing
      evidence suggesting a consistent association between AF and all forms of
      dementia. Although dementia and AF share several risk factors, the association
      appears to be independent of a history of clinical stroke and other comorbidities
      such as hypertension, heart failure, and diabetes. Proposed mechanisms linking AF
      to cognitive decline include altered hemodynamics resulting in cerebral
      hypoperfusion, inflammation, genetic factors, and silent cerebral ischemia due to
      subclinical microemboli. Evidence in support of the microembolization hypothesis
      includes the much higher incidence of silent cerebral ischemia detected in
      imaging studies in patients with AF, the association between presence of silent
      cerebral ischemia and cognitive dysfunction, and a "dose response" relationship
      between extent of silent cerebral ischemia and degree of cognitive impairment.
      Preventive therapies are currently being investigated and include
      anticoagulation, antiplatelet therapy, statins, pharmacological rhythm and rate
      control treatment strategies for AF, and catheter ablation procedures. Blinded
      Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive
      Impairment in Atrial Fibrillation (BRAIN-AF) trial is currently assessing whether
      oral anticoagulation can prevent cognitive decline in patients at low risk of
      overt stroke. Considering the strong and independent association between AF and
      neurocognitive outcomes and the major clinical implications, evidence-based
      preventive approaches are critically required to diminish the health burden from
      the scourge of dementia and related conditions.

PMID- 29173599
TI  - Bipolar Disorder and the Vascular System: Mechanisms and New Prevention
      Opportunities.
AB  - Bipolar disorder (BD) is associated with excessive prevalence and premature onset
      of cardiovascular disease (CVD). This association is observed internationally in
      clinical as well as predominantly untreated epidemiologic samples. A number of
      factors might explain this association in part, including excessive rates of
      traditional cardiovascular risk factors (CVRFs), suboptimal lifestyle behaviour s
      relating to physical activity, nutrition, and use of alcohol, tobacco, and drugs,
      and the use of psychiatric medications with propensity for causing CVRFs.
      Nonetheless, compelling findings from predominantly untreated representative
      population samples indicate the increased risk of CVD among people with BD likely
      exceeds what can be explained by these factors. In this narrative review, I
      summarize the clinical epidemiology linking BD and CVD, and the previously
      reviewed biological processes that might be contributory, including excessive
      inflammation, and summarize a growing body of literature from the author's
      research group regarding vascular factors among adolescents with BD, a group of
      patients that is highly amenable to the potential benefits of preventive
      cardiology approaches. Finally, I elaborate on a hypothesis that microvascular
      phenotypes might explain in part the "extra" risk of CVD that is not explained by
      traditional CVRFs.

PMID- 29173600
TI  - A Practical Approach to Avoiding Cardiovascular Adverse Effects of Psychoactive
      Medications.
AB  - Drugs that act on mental state, generally termed "psychoactive agents," are among
      the most widely used medications in medicine. Psychoactive agents can affect the
      cardiovascular system and must be used carefully to avoid negative cardiovascular
      consequences. In the present article we review the potential adverse
      cardiovascular consequences of psychoactive medications and provide suggestions
      for practical approaches to avoiding them. We consider adverse reactions in terms
      of: (1) arrhythmias (particularly acquired long QT syndrome); (2) blood pressure;
      (3) ventricular function; (4) effect on risk factors; (5) teratogenicity; and (6)
      drug interactions. Minimizing QT liability requires a consideration of patient
      specific risk factors and the risk profile of drugs available to treat the
      psychiatric condition. Drugs with QT-prolonging properties can be used safely,
      provided that appropriate precautions are taken. Fear of QT-prolongation should
      not deprive patients of needed psychiatric therapy. For example, one large study
      reported substantially increased all-cause mortality/hospitalization,
      death/depression-hospitalization, and death/arrhythmia-hospitalization in
      patients for whom citalopram dosage was reduced over QT-concerns after the Food
      and Drug Administration Black Box Warning. In general, attention to drug-specific
      cardiac adverse effect risks is needed, along with appropriate patient-related
      drug selection and follow-up, to detect adverse reactions early and adjust
      accordingly. Treatment should begin with low doses, followed by careful dose
      titration and adjustment of drug regimen according to clinical responses.
      Particular care is needed to minimize negative consequences on
      cardiovascular/metabolic risk profile, which might have very detrimental long
      term effects on cardiovascular health. It is crucial that fear of cardiovascular
      adverse effects not deprive patients of appropriate psychoactive drug-therapy.

PMID- 29173601
TI  - Autologous Bone Marrow Stem Cell Therapy in Patients With ST-Elevation Myocardial
      Infarction: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Randomized controlled trials (RCTs) on bone marrow stem cell (BMSC)
      therapy in ST-elevation myocardial infarction (STEMI) patients have reported
      conflicting results. Our main objective was to critically appraise and meta
      analyze best-available evidence on efficacy and safety of intracoronary
      administration of autologous BMSC therapy in STEMI patients after primary
      percutaneous coronary intervention. METHODS: We conducted a search of MEDLINE,
      PubMed, EMBASE, CENTRAL, Global Health, CINAHL, and conference proceedings in
      February 2017. Our primary outcome was all-cause mortality. Secondary and safety
      outcomes included cardiac death, heart failure, arrhythmias, repeat myocardial
      infarction, or target vessel revascularizations; or improved health-related
      quality of life, left ventricular ejection fraction, or infarct size. Summary
      relative and absolute risks were obtained using random effects models. We also
      evaluated the strength of evidence. RESULTS: A comprehensive database search
      identified 42 RCTs (3365 STEMI patients). BMSC therapy did not significantly
      decrease mortality (risk ratio, 0.71; 95% confidence interval, 0.45-1.11; I2, 0%;
      absolute risk reduction, 0.1%; 95% confidence interval, -0.71 to 0.91; 40 trials;
      3289 participants; I2, 0%; low strength of evidence). BMSC therapy had no effect
      on secondary or adverse outcomes. Trial sequential analysis for all-cause
      mortality showed no evidence of a clinically important difference, with a very
      low probability that future studies can change the current conclusion.
      CONCLUSIONS: On the basis of evidence from 42 RCTs published in the past 15
      years, we provide conclusive evidence for a lack of beneficial effect for
      autologous BMSC therapy in patients with STEMI.

PMID- 29173602
TI  - Association Between Circulating Oxidized LDL and Atherosclerotic Cardiovascular
      Disease: A Meta-analysis of Observational Studies.
AB  - BACKGROUND: Although basic research has suggested that oxidized low-density
      lipoprotein (ox-LDL) is involved in the pathogenesis of atherosclerosis,
      population observational studies have yielded conflicting results about the
      association between circulating ox-LDL and atherosclerotic cardiovascular disease
      (ASCVD). Therefore, we performed a systematic review and meta-analysis of
      currently available observational studies to verify the association between
      circulating ox-LDL and ASCVD. METHODS: We systematically searched PubMed and the
      Cochrane Library from their inception to March 27, 2017, for nested case-control
      studies, case-cohort studies, and prospective cohort studies on the relationship
      between ox-LDL and ASCVD. Studies that did not assess the hazard ratio, relative
      risk, or odds ratio of ox-LDL or did not adjust for other risk factors, or those
      without examination of ox-LDL before collection of ASCVD occurrences were
      excluded. The summarized effect size was combined using fixed effect models.
      Subgroup analyses were performed on the basis of study quality, study design,
      definition of ASCVD events, effect size types, types of ox-LDL assay, ox-LDL
      contrast level, and whether low-density lipoprotein cholesterol was adjusted in a
      multivariate model. RESULTS: A total of 12 included studies consisted of 3 nested
      case-control studies, 1 case-cohort study, 5 hospital-based cohort studies, and 3
      community-based cohort studies. The summary effect size of increased circulating
      ox-LDL was 1.79 (95% confidence interval, 1.56-2.05) for ASCVD. Similar
      associations were shown in all subgroups. CONCLUSIONS: Our findings indicate that
      increased levels of circulating ox-LDL are associated with clinical ASCVD events.
      Further well designed community-based cohort studies or intervention studies are
      needed to confirm our findings.

PMID- 29173603
TI  - Comparison of Different Automated Office Blood Pressure Measurement Devices:
      Evidence of Nonequivalence and Clinical Implications.
AB  - BACKGROUND: Automated office blood pressure (AOBP) measuring devices are
      increasingly recommended as preferred blood pressure (BP) diagnostic tools, but
      it is unclear how they compare and how clinical environments impact their
      performance. METHODS: This prospective randomized factorial parallel 4-group
      study compared BP estimates by BpTRU (VSM MedTech, Vancouver, BC, Canada) and
      Omron HEM 907 (Omron Healthcare, Kyoto, Japan) devices in closed vs open areas.
      Patients diagnosed with hypertension were recruited during office visits. After
      baseline open-room AOBP measurement with the BpTRU, patients had a second BP
      measurement with either the BpTRU or HEM 907 in either open or closed areas.
      Absolute BP levels and differences between the first and second measurements were
      compared. Diagnostic performance was also assessed. RESULTS: Two hundred fifty
      eight patients were studied. Their mean age was 66.2 +/- 12.0 years, and 62% were
      men. The mean of first AOBP estimates was 127.4/73.3 mm Hg. Analyses of
      subsequent measurements revealed no influence of open or closed areas on BP means
      and diagnostic performance. Conversely, the Omron HEM 907 exceeded BpTRU systolic
      BP measurements by 4.6 mm Hg (< 0.01) in closed areas and by 3.9 mm Hg (< 0.01)
      in open areas. The discrepancy between devices was amplified at lower BP levels.
      CONCLUSIONS: Although different areas did not influence BP estimates, the Omron
      HEM 907 significantly exceeded BpTRU measurements on average and especially at
      lower BP levels. These differences should be considered when interchanging
      devices and could have clinical decision impacts in a population of patients
      treated for hypertension. Our results support the constant use of only 1 device
      type in a given clinic.

PMID- 29173604
TI  - The Impact of Burst Exercise on Cardiometabolic Status of Patients Newly
      Diagnosed With Type 2 Diabetes.
AB  - BACKGROUND: The impact of burst high-intensity exercise on physiological,
      cardiometabolic, and biochemical variables compared with traditional moderate
      intensity continuous exercise training (MICT) has yet to be assessed in patients
      with type 2 diabetes (T2D). We compared the impact of multiple short-duration,
      high-intensity burst exercise sessions to MICT on cardiometabolic variables in
      patients with T2D. METHODS: Forty newly diagnosed patients with T2D not receiving
      lipid lowering or hypoglycemic medications were randomized to 40 minutes of MICT
      (60% of maximal heart rate) 5 days per week or 3 continuous bursts of 12 minutes
      of high-intensity exercise (85% of maximal heart rate) 5 days per week for 3
      months. Body mass index, hemoglobin A1C (HbA1C), and lipid profile were assessed
      before and after 3 months of exercise training. RESULTS: Burst exercise resulted
      in greater body mass index reduction than did MICT (-2.1 +/- 1.2 kg/m2 vs -0.7 +/
      0.7 kg/m2, respectively; P < 0.05). There was a greater reduction at 3 months (P
      < 0.05) in HbA1C levels in the burst exercise group (8.14% +/- 0.49% to 7.32% +/-
      0.39%) compared with the MICT group (8.18% +/- 0.35% to 7.94% +/- 0.41%).
      Compared with MICT, burst exercise was associated with a greater reduction in low
      density lipoprotein cholesterol (-11 vs -4%; P < 0.05) and a greater increase in
      high-density lipoprotein cholesterol (22% vs 3%; all P < 0.05). After 3 months,
      patients in the burst exercise group attained greater exercise time on the
      treadmill (exercise capacity) than did those prescribed MICT (6.87 +/- 1.44
      minutes vs 5.40 +/- 1.96 minutes; P < 0.001). CONCLUSIONS: Findings from the
      current study support better cardiometabolic benefits of burst exercise compared
      with MICT over 3 months in patients with newly diagnosed T2D.

PMID- 29173605
TI  - Prognostic Value of Psoas Muscle Area and Density in Patients Who Undergo
      Cardiovascular Surgery.
AB  - BACKGROUND: Low skeletal muscle density, determined using computed tomography
      (CT), has yet to be examined in terms of muscle function and prognostic
      capability in patients who require open cardiovascular surgery. This study was
      performed to examine whether psoas muscle area and density, determined using CT,
      are associated with postoperative mortality in patients who undergo
      cardiovascular surgery. METHODS: We reviewed the findings in 773 consecutive
      patients who underwent preoperative CT imaging, including the level of the third
      lumbar vertebra for clinical purposes. We measured grip strength, gait speed, and
      6-minute walking distance to assess muscle function before hospital discharge.
      Skeletal muscle area was calculated from psoas muscle cross-sectional area (in
      squared centimeters) on preoperative CT images at the level of the third lumbar
      vertebra divided by the square of the patient's height in metres to give the
      skeletal muscle index (SMI). Skeletal muscle density determined by muscle
      attenuation (MA) was calculated by measuring the average Hounsfield units of the
      psoas muscle cross-sectional area. RESULTS: The mean age of the study population
      was 65.0 +/- 13.1 years, and 64.7% of the patients were male. Multivariate
      logistic regression analysis and multivariate Cox regression analysis showed that
      low MA, but not SMI, was significantly associated with muscle function, and all
      cause mortality (P < 0.05). Kaplan-Meier analysis showed that low MA, but not low
      SMI, predicted mortality (P = 0.014). CONCLUSIONS: Low skeletal muscle density,
      but not skeletal muscle area, predicted poorer muscle function and mortality in
      patients who undergo cardiac surgery.

PMID- 29173606
TI  - Antiplatelet Effect of Different Loading Doses of Ticagrelor in Patients With Non
      ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary
      Intervention: The APELOT Trial.
AB  - BACKGROUND: We hypothesized that a high ticagrelor loading dose (LD) may improve
      platelet inhibition in patients with non-ST-elevation acute coronary syndrome
      (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: This
      interventional multicentre open-label trial randomized 278 patients with NSTE-ACS
      to a high (360 mg) or conventional (180 mg) ticagrelor LD. The primary outcome
      was the platelet reactivity index (PRI) 1 hour after administration of the LD.
      Secondary outcomes included PRI at 0.5 hour, 1 hour, 8 hours, and 24 hours;
      periprocedural myocardial infarction (PMI); major cardiac adverse events; and
      bleeding events. RESULTS: Two hundred sixty-two patients completed the major end
      points. PRI was lower in the high-LD group than in the conventional-LD group at
      any time point (all, P < 0.05), including at 1 hour (12.2% vs 16.7%; P = 0.023).
      At 0.5 hour, the high-LD group showed a lower high-platelet reactivity rate
      (49.6% vs 60.2%; P = 0.013) and a higher low-platelet reactivity rate (24.8% vs
      12.8%; P = 0.017) than did the conventional LD group. No significant differences
      in the bleeding rates were found between the 2 groups (14% vs 14.3%). Four cases
      of PMI and 1 death in each group, as well as 1 acute myocardial infarction in the
      conventional LD group, occurred. There was no stroke, target lesion
      revascularization, or target vessel revascularization. CONCLUSIONS: Doubling the
      ticagrelor LD achieved faster onset and greater platelet inhibition without an
      increase in adverse events in patients with NSTE-ACS undergoing PCI.

PMID- 29173607
TI  - Clinical Features and Outcomes of Acute Coronary Syndrome in Women With Previous
      Pregnancy Complications.
AB  - BACKGROUND: Women with previous cardiometabolic complications of pregnancy
      experience double the risk of cardiovascular disease. However, few data exist on
      the clinical effect of these complications at the time of an acute coronary
      syndrome (ACS). The objective of this work was to compare risk factors, clinical
      features, and outcomes among women with premature ACS with or without previous
      pregnancy complications (gestational diabetes and/or hypertensive disorders of
      pregnancy). METHODS: Data were obtained from a multicentre cohort of individuals
      hospitalized with premature ACS. A total of 251 parous women were included and
      provided obstetric history and blood samples. They were followed for the
      development of major adverse cardiac events at 12 months. RESULTS: At
      presentation with ACS, women with a previous pregnancy complication (38%) were
      slightly younger than were women without such complications (47.4 +/- 6.2 vs 49.1
      +/- 5.6 years; P = 0.002). They also had more traditional atherosclerotic risk
      factors. Specifically, women with previous preeclampsia were more likely to have
      chronic hypertension and an elevated ratio of soluble fms-like tyrosine
      kinase:placental growth factor. There was no between-group difference in Global
      Registry of Acute Coronary Events (GRACE) score or troponin tertile but there was
      a trend toward higher risk of ST-elevation myocardial infarction in women who had
      a previous pregnancy complication (odds ratio, 1.80; 95% confidence interval,
      1.00-3.23; P = 0.05). There was also an increased risk of recurrent ACS at 12
      months in women with previous preeclampsia (hazard ratio, 6.79; 95% confidence
      interval, 1.37-33.63; P = 0.02). CONCLUSIONS: Among a cohort of women with ACS,
      previous pregnancy complications were associated with more severe disease and
      poorer outcome.

PMID- 29173608
TI  - The Relationship Between Cardiologist Care and Clinical Outcomes in Patients With
      New-Onset Atrial Fibrillation.
AB  - BACKGROUND: Increased mortality is well described in patients with atrial
      fibrillation (AF), primarily related to death from cardiovascular causes. One may
      hypothesize that cardiology care may be associated with a reduction in
      cardiovascular deaths in patients with AF, thereby improving their overall
      survival. The aim of this study was to assess the association between
      cardiologist care and clinical outcomes, including all-cause mortality, in
      patients with new-onset AF. METHODS: This was a retrospective population-level,
      propensity score-matched cohort study of patients aged 20-80 years with new-onset
      AF presenting to an emergency department in Ontario, Canada between 2010 and
      2012. Patients who saw a cardiologist within 1 year of the initial diagnosis were
      matched to patients who did not see a cardiologist. Linked administrative
      databases were used for cohort construction and allow for 1-year follow-up to
      assess for the clinical end points of death, hospitalization for AF, stroke
      syndromes, bleeding, and heart failure. RESULTS: Cardiologist care was associated
      with a lower 1-year rate of death (5.3% vs 7.7%; hazard ratio, 0.68; 95%
      confidence interval, 0.55-0.84), despite an increased rate of hospitalizations
      for AF (17.9% vs 8.2%), stroke syndromes (1.7% vs 0.5%), bleeding (3.1% vs 2.0%),
      and heart failure (3.2% vs 1.4%). CONCLUSIONS: Cardiologist care was associated
      with a reduction in death in patients with new-onset AF. Further study to obtain
      a greater understanding of the processes of care associated with the observed
      survival improvement is warranted.

PMID- 29173609
TI  - Effects of Patent Foramen Ovale Closure on Obstructive Sleep Apnea Syndrome:
      PCOSA Study.
AB  - BACKGROUND: Previous studies have shown a higher prevalence of patent foramen
      ovale (PFO) in patients with obstructive sleep apnea syndrome (OSAS). Right to
      left shunting through a PFO may be encouraged by the respiratory physiology of
      OSAS, contributing to the disease pathophysiology. We assessed whether PFO
      closure would improve respiratory polygraphy parameters compared with baseline
      measurements in patients with OSAS. METHODS: Twenty-six patients with newly
      diagnosed OSAS and a moderate-large PFO (prevalence, 18% of 143 patients
      screened) were referred for PFO closure. The oxygen desaturation index (ODI),
      apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), 6-minute walk test
      (6MWT), and Sleep Apnea Quality of Life Index (SAQLI) results were compared in
      these patients at baseline (before continuous positive pressure ventilation
      [CPAP]) and at 6-month follow-up (after interrupting CPAP for 1 week). RESULTS:
      All PFOs were safely sealed at 6 months, as confirmed by repeated transthoracic
      echocardiography. The ODI (44.8 [interquartile range (IQR), 31.2-63.5) vs 42.3
      [IQR, 34.0-60.8]; P = 0.89) and AHI (47.9 [IQR, 31.5-65.2] vs 42.3 [IQR, 32.1
      63]; P = 0.99) did not change after PFO closure nor did the 6MWT, although the
      ESS (13.0 [IQR, 12.0-16.8] vs 6.0 [IQR, 4.0-8.8]; P < 0.001) and the SAQLI (3.4
      [IQR, 2.8-4.3] vs 4.4 [IQR, 3.9-5.3]; P < 0.001) did improve. CONCLUSIONS: The
      prevalence of PFO in OSAS appears to be no higher than that in the general
      population. Although PFO closure is safe and effective, it did not improve
      respiratory polygraphy measures of OSAS severity. The improvement in the ESS and
      SAQLI likely reflect residual benefits from CPAP.

PMID- 29173610
TI  - Endothelial Nitric Oxide Synthase-Induced Hypertrophy and Vascular Dysfunction
      Contribute to the Left Ventricular Dysfunction in Caveolin-1-/- Mice.
AB  - BACKGROUND: Caveolin-1 (Cav1)-/- mice display impaired development of left
      ventricular pressure and increased left ventricular wall thickness but no dilated
      ventricle; these are typical findings in patients with heart failure with
      preserved ejection fraction (HfpEF). Aiming to clarify if dysfunctional
      endothelial nitric oxide synthase (eNOS) influences cardiomyocyte contractility,
      cardiac conduction system, or afterload/vascular resistance, we studied Cav1-/
      /eNOS-/- mice. METHODS: Cardiac function was assessed in vivo by pressure-volume
      catheterization of the left ventricle, echocardiography and electrocardiography.
      In addition, isolated tissue experiments were performed to evaluate cardiomyocyte
      contractility (atria) and vessel morphology and function (aorta). Histology,
      immunoblotting and quantitative polymerase chain reaction were applied to
      characterise radical formation and oxidative stress in the heart. RESULTS:
      Cardiac hypertrophy was completely reversed in Cav1-/-/eNOS-/- mice. The impaired
      pump function in Cav1-/- mice was significantly improved in Cav1-/-/eNOS-/- mice,
      but no complete alignment with eNOS-/- controls was achieved, indicating an
      additional eNOS-independent mechanism contributing to HFpEF in Cav1-/- mice. It
      is unlikely that frequently occurring arrhythmias contributed to HFpEF in Cav1-/-
      mice. In contrast, numerous eNOS-dependent and eNOS-independent vascular
      abnomalities could explain the cardiac phenotypes of Cav1-/- mice. CONCLUSIONS:
      Synergistic effects between eNOS-related cardiac hypertrophy and vascular
      hypercontractility appear to underlie the left ventricular dysfunction in Cav1-/
      mice. These findings provide insights relevant to the poorly understood
      pathophysiology of HFpEF.

PMID- 29173611
TI  - A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch
      Immediately Beyond the Conduction Block.
AB  - This report demonstrates the feasibility of pacing the left bundle branch (LBB)
      immediately beyond the conduction block to functionally restore the impaired His
      Purkinje conduction system in a patient with heart failure and left bundle branch
      block (LBBB). The pacing required only a low pacing output (0.5 volts/0.5 ms) to
      correct the LBBB with accompanying right BBB on the electrocardiogram. Over 1
      year of follow-up, the patient had a significant improvement in clinical outcome
      and echocardiographic measurements. The case shows a novel pacing strategy for
      patients with BBB that affects many patients with heart failure.

PMID- 29173612
TI  - A Case of Spontaneous Coronary Artery Dissection Complicated by Free Wall
      Rupture.
AB  - Spontaneous coronary artery dissection (SCAD) is an unusual and underdiagnosed
      cause of nonatherosclerotic acute coronary syndrome (ACS). Patients might present
      in various ways including chest pain, ST-elevation ACS, ventricular arrhythmia,
      and sudden cardiac death. In a few reports, it manifested initially as cardiac
      tamponade. The association of SCAD with free wall rupture is extremely rare. We
      present a unique case of a 70-year-old woman who initially presented with non-ST
      elevation ACS and was found to have SCAD on angiography, which was subsequently
      complicated by cardiac tamponade with free wall rupture.

PMID- 29173613
TI  - Pregnancy in Women With Repaired Truncus Arteriosus: A Case Series.
AB  - Pregnancy in women with repaired truncus arteriosus (TA) is rare. We report the
      outcomes of 8 pregnancies in 4 women with surgically repaired TA. None of the
      women had adverse cardiac events during pregnancy. Two pregnancies, both in the
      same woman, were complicated by hypertensive disorders of pregnancy. The birth
      weight was less than the 10th percentile for gestational age in 3 pregnancies.
      Although women with repaired TA can do well during pregnancy, they require
      careful preconception assessment and surveillance.

PMID- 29173615
TI  - Inactivation of murine norovirus and hepatitis A virus on fresh raspberries by
      gaseous ozone treatment.
AB  - Raspberries are vulnerable products for which industrial treatment solutions
      ensuring both food safety and sensory quality are not easily applicable.
      Raspberries have been associated with numerous foodborne outbreaks in recent
      decades. Ozone has been proven effective as a drinking water treatment against
      pathogenic microorganisms. Nevertheless, to date, little information is available
      regarding the effect of gaseous ozone on viruses in food matrices. A comparison
      of the effect of gaseous ozone on murine norovirus (MNV-1) and hepatitis A virus
      (HAV) adsorbed on fresh raspberries was performed. Infectious MNV-1 was highly
      inactivated (>3.3 log10) by ozone (3 ppm, 1 min). The raspberry matrix seems to
      enhance inactivation by ozone compared to water. The same treatment was observed
      to have little effect on HAV even for the highest dose under the tested
      conditions (5 ppm, 3 min). Ozone treatment (5 ppm, 3 min) did not affect the
      appearance of raspberries even after three days post-treatment. No ozone effect
      was observed on the genomes detected by RT-PCR on both tested viruses,
      irrespective of the matrix or tested doses used. Gaseous ozone could therefore be
      a good candidate for human norovirus inactivation on raspberries but new
      conditions are needed for it to have significant effects on HAV inactivation.

PMID- 29173614
TI  - Pregnancy After Transcatheter Pulmonary Valve Implantation.
AB  - Transcatheter pulmonary valve implantation (TPVI) is a relatively new method of
      treating patients with significant pulmonary regurgitation or pulmonary stenosis,
      or both, after reconstruction of the right ventricular outflow tract. It is an
      attractive alternative to conduit replacement in this group of patients, who are
      typically young and active. This report includes 4 young women who after
      successful TPVI became pregnant and gave birth. Transthoracic echocardiography,
      cardiopulmonary exercise testing, and cardiac magnetic resonance imaging were
      performed in all patients. The results suggest that pregnancy and delivery after
      successful TPVI is safe when the appropriate precautions have been taken.

PMID- 29173616
TI  - Efficacy of Pseudomonas graminis CPA-7 against Salmonella spp. and Listeria
      monocytogenes on fresh-cut pear and setting up of the conditions for its
      commercial application.
AB  - Pseudomonas graminis CPA-7 has been reported to control foodborne pathogens on
      fresh-cut apple, peach and melon. The first aim of this study was to assess its
      antagonistic activity against Salmonella spp. and L. monocytogenes on fresh-cut
      pear. CPA-7 was able to control both pathogens on fresh-cut pear stored in air
      conditions at 5, 10 and 20  degrees C. However, when CPA-7 antagonistic effect
      was tested by simulating commercial application (with antioxidant solution and
      passive modified atmosphere packaging), its effect decreased and no reductions of
      foodborne pathogens were reported at 10  degrees C. Therefore, the second aim was
      to optimise the antioxidant solution and the packaging in order to retain its
      antagonistic capacity. The selected antioxidant solution was 2% ascorbic acid +2%
      sodium citrate +1% CaCl2 according to growth and effect of CPA-7. Film
      permeability, which affects gas composition inside fruit packages, influenced CPA
      7 efficacy. If the biopreservative strain is used, film has to be sufficiently
      gas permeable to allow CPA-7 function and at the same time to maintain product
      quality.

PMID- 29173617
TI  - Identification of Brucella genus and eight Brucella species by Luminex bead-based
      suspension array.
AB  - Globally, unpasteurized milk products are vehicles for the transmission of
      brucellosis, a zoonosis responsible for cases of foodborne illness in the United
      States and elsewhere. Existing PCR assays to detect Brucella species are
      restricted by the resolution of band sizes on a gel or the number of fluorescent
      channels in a single real-time system. The Luminex bead-based suspension array is
      performed in a 96-well plate allowing for high throughput screening of up to 100
      targets in one sample with easily discernible results. We have developed an array
      using the Bio-Plex 200 to differentiate the most common Brucella species: B.
      abortus, B. melitensis, B. suis, B. suis bv5, B. canis, B. ovis, B. pinnipedia,
      and B. neotomae, as well as Brucella genus. All probes showed high specificity,
      with no cross-reaction with non-Brucella strains. We could detect pure DNA from
      B. abortus, B. melitensis, and genus-level Brucella at concentrations of <=5
      fg/MUL. Pure DNA from all other species tested positive at concentrations well
      below 500 fg/MUL and we positively identified B. neotomae in six artificially
      contaminated cheese and milk products. An intra-laboratory verification further
      demonstrated the assay's accuracy and robustness in the rapid screening (3-4 h
      including PCR) of DNA.

PMID- 29173618
TI  - Association between bacterial survival and free chlorine concentration during
      commercial fresh-cut produce wash operation.
AB  - Determining the minimal effective free chlorine (FC) concentration for preventing
      pathogen survival and cross-contamination during produce washing is critical for
      developing science- and risk-based food safety practices. The correlation between
      dynamic FC concentrations and bacterial survival was investigated during
      commercial washing of chopped Romaine lettuce, shredded Iceberg lettuce, and
      diced cabbage as pathogen inoculation study during commercial operation is not
      feasible. Wash water was sampled every 30 min and assayed for organic loading,
      FC, and total aerobic mesophilic bacteria after chlorine neutralization. Water
      turbidity, chemical oxygen demand, and total dissolved solids increased
      significantly over time, with more rapid increases in diced cabbage water.
      Combined chlorine increased consistently while FC fluctuated in response to rates
      of chlorine dosing, product loading, and water replenishment. Total bacterial
      survival showed a strong correlation with real-time FC concentration. Under
      approximately 10 mg/L, increasing FC significantly reduced the frequency and
      population of surviving bacteria detected. Increasing FC further resulted in the
      reduction of the aerobic plate count to below the detection limit (50 CFU/100
      mL), except for a few sporadic positive samples with low cell counts. This study
      confirms that maintaining at least 10 mg/L FC in wash water strongly reduced the
      likelihood of bacterial survival and thus potential cross contamination of washed
      produce.

PMID- 29173619
TI  - Predictive modeling of bacterial growth in ready-to-use salted napa cabbage
      (Brassica pekinensis) at different storage temperatures.
AB  - The objectives of the current study were to investigate the fate of microbial
      indicators [aerobic plate counts (APC), total coliforms (TC), and lactic acid
      bacteria (LAB)] in commercial salted napa cabbages during storage conditions at
      different temperatures (5, 22, and 30  degrees C, for up to 72 h) and to develop
      a predictive growth model using the modified Gompertz equation to determine shelf
      life. Microbial population sizes (initial log CFU g-1: APC, 5.1; TC, 3.0; LAB,
      3.7) remained stable at 5  degrees C, but rapidly increased by 2-4 log CFU g-1
      within 12 h at 22 and 30  degrees C; furthermore, the pH of salted napa cabbages
      decreased significantly (P < 0.05: initial pH 6.3; final pH 4.1-4.4) due to LAB
      fermentation. The pH showed a negative correlation with all bacterial groups and
      did not prevent the growth of TC during storage. According to the modified
      Gompertz model (R2 ? 0.97), the highest MUmax was observed for LAB at 30  degrees
      C [0.61 log CFU h-1], while the lowest was noted for TC at 5  degrees C [0.04 log
      CFU h-1]. Shelf-life was determined using APC (7.7 log CFU g-1) and LAB (6.0 log
      CFU g-1) limits; the microbiological acceptability period of salted napa cabbage
      was predicted to be 12.6 and 9.3 h at 22 and 30  degrees C, respectively. Thus,
      consumers should use the product within 12 h of storage at room temperature (more
      quickly in the summer (9 h)), or store it in a refrigerator. The presented
      research proposes a shelf-life modeling of commercial salted napa cabbages, which
      may be used as a scientific basis for product quality control and issuing
      appropriate guidance for consumer use at home.

PMID- 29173620
TI  - Loop-Mediated Isothermal Amplification-Lateral-Flow Dipstick (LAMP-LFD) to detect
      Toxoplasma gondii oocyst in ready-to-eat salad.
AB  - The apicomplexan parasite Toxoplasma gondii is the causative agent of
      toxoplasmosis, a foodborne zoonosis with a global distribution and estimated to
      cause up to 20% of the total foodborne disease burden in Europe. Association
      between T. gondii infection and the consumption of unwashed raw fruits and
      vegetables contaminated with oocysts has been reported and the increasing habit
      to eat pre-washed ready-to-eat salads poses a new potential risk for consumers.
      It is therefore important to trace the occurrence of potential contamination with
      this parasite to guarantee the safety of ready-to-eat vegetables. Detection of T.
      gondii in vegetables by molecular techniques has been achieved but low
      sensitivity (PCR) or expensive equipments (qPCR) limit routine applicability.
      Here, we describe the development and validation of a sensitive and robust method
      relying on a LAMP assay, targeting the 529 bp locus, to detect T. gondii oocysts
      down to 25 oocysts/50 g in ready-to-eat baby lettuce. The LAMP has been also
      adapted for a faster visualization of the result by a lateral flow dipstick
      chromatographic detection method.

PMID- 29173621
TI  - Polyphasic approach to study physico-chemical, microbiological and sensorial
      characteristics of artisanal Nicastrese goat's cheese.
AB  - Nicastrese goat's cheese is produced in the South of Italy under traditional
      procedures, from raw goat milk without any starter cultures addition. Samples
      from milk to ripened cheese provided by 4 different farms were subjected to a
      polyphasic approach to study their physico-chemical, microbiological and
      sensorial characteristics. In addition, volatile organic compounds formation in
      the final products was studied. Overall, gross composition and microbiological
      data revealed a significant variability among samples, which was confirmed by
      both the volatile organic compounds generated in the final products and by the
      sensorial data. Conventional technique allowed us to identify 720 isolates,
      mainly belonging to Lactococcus lactis, Lactobacillus plantarum, Lactobacillus
      casei, Lactobacillus brevis, Leuconostoc mesenteroides, and Enterococcus
      faecalis. Culture-independent methods revealed shifts in the microbial community
      structure, with an increase in biodiversity of metabolically active bacterial
      species, from milk to cheese samples. Analysis of volatile organic compounds
      (VOCs) allowed the identification of 36 compounds; free fatty acids and ketones
      represented the main detected, followed by alcohols and esters. Moreover,
      statistical analysis was performed in order to correlate VOCs to bacterial
      species. Data showed that ester compounds as well as alcohol and aldehydes were
      positively correlated to NSLAB, indicating that the occurrence of L. casei, L.
      plantarum and L. brevis species is relevant for the VOCs formation in the final
      product.

PMID- 29173622
TI  - Impact of relative humidity, inoculum carrier and size, and native microbiota on
      Salmonella ser. Typhimurium survival in baby lettuce.
AB  - The effects of relative humidity (RH), fluctuating climate conditions, inoculum
      size and carrier on the survival of Salmonella enterica serovar Typhimurium on
      baby lettuce in environmental test chambers were studied. Buffered peptone water
      (BPW), distilled water (DW), and irrigation water (IW) were compared as inoculum
      carriers. Additionally, survival of Salmonella in suspensions prepared using
      filtered and unfiltered IW was assessed. Salmonella Typhimurium survived better
      on baby lettuce plants at high RH independently of the inoculum size. When
      lettuce plants were grown under fluctuating environmental conditions, Salmonella
      survival was similar under both RH conditions. Regarding the inoculum carrier,
      the inoculated microorganism survived better on lettuce plants when BPW was used
      as carrier both at high and low RH. Survival rate of Salmonella in IW was
      affected by the presence of native microbiota. Native microbiota present in IW
      did not affect survival of Salmonella or the levels of mesophilic bacteria on the
      baby lettuce leaves. The information obtained in the present study contributes to
      the knowledge on the effect of environmental conditions on pathogenic bacteria
      survival on growing edible plants. These results are useful when selecting the
      methodology to carry out experimental studies on the survival of microbial
      pathogens under different pre-harvest conditions.

PMID- 29173623
TI  - Wheat endophytic lactobacilli drive the microbial and biochemical features of
      sourdoughs.
AB  - The aim of this study was to assess whether wheat endophytic lactic acid bacteria
      (LAB) are able to dominate in sourdough ecosystem. To do that, a first
      experimental phase considered doughs produced under semi-sterile conditions and
      singly inoculated with different strains of endophytic LAB and Lactobacillus
      sanfranciscensis A4 isolated from sourdough. Notwithstanding the high frequency
      of Lactobacillus plantarum in the sourdoughs prepared in laboratory, only one of
      the starter strains, L. plantarum LB2, was detected after five days of back
      slopping. Subsequently, the ability of this strain to dominate traditional
      sourdoughs was evaluated at bakery and laboratory level. Contamination of
      sourdoughs with L. plantarum LB2 caused an increased number of LAB and,
      accordingly, higher acidification, compared to the sourdoughs before this event.
      After six days of propagation, the wheat endophytic strain L. plantarum LB2 was
      retrieved as a component of the bacterial population, in all the sourdoughs and
      regardless of the place of propagation. In addition, the contamination event
      caused a modification of the lactic acid bacterium biota, which in turn
      influenced some sourdoughs biochemical features. In conclusion, this study showed
      that wheat endophytic LAB could represent a potential reservoir for selecting
      robust strains to be used as sourdough starters.

PMID- 29173624
TI  - Causal agents of Fusarium head blight of durum wheat (Triticum durum Desf.) in
      central Italy and their in vitro biosynthesis of secondary metabolites.
AB  - Durum wheat samples harvested in central Italy (Umbria) were analyzed to:
      evaluate the occurrence of the fungal community in the grains, molecularly
      identify the Fusarium spp. which are part of the Fusarium head blight (FHB)
      complex and characterize the in vitro secondary metabolite profiles of a subset
      of Fusarium strains. The Fusarium genus was one of the main components of the
      durum wheat fungal community. The FHB complex was composed of eight species:
      Fusarium avenaceum (61%), F. graminearum (22%), F. poae (9%), F. culmorum (4%),
      F. proliferatum (2%), F. sporotrichioides (1%), F. sambucinum (0.5%) and F.
      langsethiae (0.5%). F. graminearum population was mainly composed of the 15
      acetyldeoxynivalenol chemotype, while, F. culmorum population was composed of the
      3-acetyldeoxynivalenol chemotype. In vitro characterization of secondary
      metabolite biosynthesis was conducted for a wide spectrum of substances, showing
      the mycotoxigenic potential of the species complex. F. avenaceum strains were
      characterized by high enniantin and moniliformin production. F. graminearum
      strains were in prevalence deoxynivalenol producers. F. poae strains were
      characterized by a high biosynthesis of beauvericin like the F. sporotrichioides
      strain which was also found to be a high T-2/HT-2 toxins producer. Production of
      aurofusarin, butenolide, gibepyrone D, fusarin C, apicidin was also reported for
      the analyzed strains.

PMID- 29173625
TI  - Biofilm formation by Salmonella spp. in catfish mucus extract under industrial
      conditions.
AB  - The objective of this study was to determine the effect of strain and temperature
      on the growth and biofilm formation of Salmonella spp. in high and low
      concentrations of catfish mucus extract on different food-contact surfaces at 22 
      degrees C and 10  degrees C. The second objective of this study was to evaluate
      the efficacy of disinfectants at recommended concentrations and contact times for
      removing Salmonella biofilms cells on a stainless steel surface containing
      catfish mucus extract. Growth and biofilm formation of all Salmonella strains
      increased with higher concentrations of catfish mucus extract at both 10  degrees
      C and 22  degrees C. In 15 MUg/ml of catfish mucus extract inoculated with 3 log
      CFU/ml, the biofilm levels of Salmonella on stainless steel surface reached to
      3.5 log CFU/cm2 at 10  degrees C or 5.5 log CFU/cm2 at 22  degrees C in 7 days.
      In 375 MUg/ml of catfish mucus extract inoculated with 3 log CFU/ml, the biofilm
      levels of Salmonella on the stainless steel surface reached 4.5 log CFU/cm2 at 10
      degrees C and 6.5 log CFU/cm2 at 22  degrees C in 7 days. No differences were
      observed between Salmonella strains tested for biofilm formation in catfish mucus
      extract on the stainless steel surface. The biofilm formation by Salmonella
      Blockley (7175) in catfish mucus extract was less (P < 0.05) on buna-N rubber
      when compared to stainless steel, polyethylene and polyurethane surfaces.
      Salmonella biofilm cells were not detectable on the stainless steel surface after
      treatment with a mixture of disinfectants but were still present when single
      compound disinfectants were used.

PMID- 29173626
TI  - Microbial dynamics during production of lesser mealworms (Alphitobius diaperinus)
      for human consumption at industrial scale.
AB  - In this study, the microbial dynamics during an industrial production cyle of
      lesser mealworms (Alphitobius diaperinus), sold for human consumption, were
      characterised. The microbial numbers as well as the microbial diversity were
      generally higher for the substrate, existing of remaining feed, faeces and
      exuviae, than for the larvae. Most of the species-level operational taxonomic
      units, identified using Illumina MiSeq sequencing, that were present in the feed
      were also detected in the larvae and vice versa. However, bacterial diversity
      decreased in the larvae during rearing. These results suggested that the feed is
      an important determinant of the insect bacterial community, but that some
      bacterial species show a competitive advantage inside the insect gut and become
      dominant. A blanching treatment of the larvae after harvest reduced most
      microbial counts, but the number of aerobic endospores remained at 4.0 log cfu/g.
      Whereas food pathogens Salmonella spp., Listeria monocytogenes, Bacillus cereus
      or coagulase-positive staphylococci were not detected in our study, fungal
      isolates corresponding to the genera Aspergillus and Fusarium were recovered.
      Therefore, it cannot be excluded that mycotoxins were present. The results of
      this study contribute to a better understanding of the microbial dynamics and
      food safety aspects during the production of edible insects.

PMID- 29173627
TI  - Correlation between slaughter practices and the distribution of Salmonella and
      hygiene indicator bacteria on pig carcasses during slaughter.
AB  - This study investigated the distribution of hygiene indicator bacteria and
      Salmonella on pig carcasses. Moreover, the relation between hygiene indicator
      counts and Salmonella presence as well as associations between specific slaughter
      practices and carcass contamination were determined for each carcass area. Seven
      Belgian pig slaughterhouses were visited three times to swab five randomly
      selected carcasses at nine different areas, after evisceration and trimming.
      Information about slaughter practices was collected using a questionaire. In all
      samples, the E. coli and Salmonella presence was analyzed and Enterobacteriaceae
      and total aerobic bacteria were quantified. Average total aerobic counts ranged
      from 3.1 (loin, pelvic duct, ham) to 4.4 log10 CFU/cm2 (foreleg). Median
      Enterobacteriaceae numbers varied between 0.4 (ham) an 1.8 log10 CFU/cm2
      (foreleg). E. coli and Salmonella presence ranged from 15% (elbow) to 89%
      (foreleg) and 5% (elbow) to 38% (foreleg), respectively. Positive relations were
      found between hygiene indicator counts and Salmonella presence at the head,
      sternum, loin and throat. Several slaughter practices, such as splitting the head
      and incising tonsils, were associated with higher levels of hygiene indicator
      bacteria and Salmonella. These findings can be used to educate slaughterhouse
      personnel and estimate the public health risk involved in consumption of
      different pork cuts.

PMID- 29173628
TI  - Survival of Escherichia coli O157:H7 during the manufacture and ripening of
      Cacioricotta goat cheese.
AB  - The aim of this study was to assess the growth and survival of Escherichia coli
      O157:H7 during the manufacturing and ripening of Cacioricotta goat cheese. Goat
      milk was artificially contaminated with E. coli O157:H7 and the bacterial load
      was monitored from production up to 90 days of ripening. Goat milk was inoculated
      with 102 cfu ml-1 of E. coli O157:H7 and the bacterial count of the curd at time
      zero was 2.31 log10 cfu g-1. During the first day of ripening, the bacterial load
      has increased to 5.73 log10 cfu g-1 to more than 6.20 log10 cfu g-1 during the
      first week. The bacterial load remained constant up to 28 days and then slightly
      decreased until the end of ripening, with values of aw and pH of 0.88 and 5.41
      respectively. The results of this study highlighted that E. coli O157:H7 is able
      to survive the manufacturing process and they suggest that the 90-day period of
      ripening alone is insufficient to remove E. coli O157:H7 in contaminated
      Cacioricotta goat cheese. Moreover, these results support the assumption that the
      presence of a low contamination of milk with E. coli O157:H7 could represent a
      potential source of infection and a threat to consumers.

PMID- 29173629
TI  - Hydrogen sulfide synthesis in native Saccharomyces cerevisiae strains during
      alcoholic fermentations.
AB  - In order to diminish the undesirable impact of hydrogen sulfide (H2S) on wine,
      H2S synthesis was evaluated at phenotypic and transcriptional levels in 16
      strains of Saccharomyces cerevisiae, which comprised 12 natural isolates, three
      commercial strains, and one laboratory heterozygote. Strain-dependent and multi
      gene participation traits were evident, and high gene activity did not
      necessarily elevated H2S levels. When the variation of gene expression was
      analyzed between fermentation stages in each strain, similarities among some
      strains related to H2S formation. UCD522 and seven strains with low H2S
      production were grouped together based on cluster analysis and fold-change
      analysis. They displayed a negative relationship between activity of MET17, HOM2,
      SER33 and CYS4 and H2S formation, suggesting the role of biosynthesis of sulfur
      containing amino acids. In the CECLFE1225, CECLFE1226 and UCD819 strains,
      transcriptional variation in MET3, MET5 and MET10 might account for the changes
      in H2S amount. High levels of HOM2 and SER33 expression were implicated with the
      H2S phenotype of CECGM1 (H2S-free strain). MET1 may be a key gene in sulfide
      biosynthesis owing to its involvement in almost all strains. This study furthers
      the understanding of H2S formation in different S. cerevisiae strains and the
      industrial application of natural isolates.

PMID- 29173630
TI  - Aroma profiling of an aerated fermentation of natural grape must with selected
      yeast strains at pilot scale.
AB  - The use of non-Saccharomyces strains in aerated conditions has proven effective
      for alcohol content reduction in wine during lab-scale fermentation. The process
      has been scaled up to 20 L batches, in order to produce lower alcohol wines
      amenable to sensory analysis. Sequential instead of simultaneous inoculation was
      chosen to prevent oxygen exposure of Saccharomyces cerevisiae during
      fermentation, since previous results indicated that this would result in
      increased acetic acid production. In addition, an adaptation step was included to
      facilitate non-Saccharomyces implantation in natural must. Wines elaborated with
      Torulaspora delbrueckii or Metschnikowia pulcherrima in aerated conditions
      contained less alcohol than control wine (S. cerevisiae, non-aerated). Sensory
      and aroma analysis revealed that the quality of mixed fermentations was affected
      by the high levels of some yeast amino acid related byproducts, which suggests
      that further progress requires a careful selection of non-Saccharomyces strains
      and the use of specific N-nutrients.

PMID- 29173631
TI  - The microbiota of eight species of dehydrated edible seaweeds from North West
      Spain.
AB  - The microbiota of eight species (Chondrus crispus, Himanthalia elongata,
      Laminaria ochroleuca, Palmaria palmata, Porphyra umbilicalis, Saccharina
      latissima, Ulva lactuca and Undaria pinnatifida) of edible seaweeds collected in
      North West Spain, marketed as dehydrated product, was quantitatively determined
      on nine solid media. Representative colonies were selected from solid culture
      media. The isolated microorganisms were identified by means of morphological
      characteristics, 16S rDNA sequencing and biochemical tests. U. pinnatifida was
      the seaweed species showing the most abundant microbial population, with counts
      on Marine agar up to 7.7 log cfu/g in individual samples and 5.0 log cfu/g as the
      mean value, and counts of coliforms up to 4.6 log cfu/g in individual samples and
      2.4 log cfu/g as the mean value. The 225 identified bacterial isolates belonged
      to 11 families, 27 genera and 56 species. Bacillaceae was the family accounting
      for the highest number of isolates (111) followed by Enterobacteriaceae (60),
      Bacillales Family XII Incertae Sedis (20), Planococcaceae (11), Moraxellaceae
      (7), Paenibacillaceae (5) and Pseudomonadaceae (5). Bacterial species showing the
      highest occurrence in dehydrated seaweeds were Bacillus megaterium, B.
      licheniformis, Pantoea sp. and termoresistant Pantoea sp. Four of the Bacillus
      species isolated from dehydrated seaweeds (B. cereus, B. licheniformis, B.
      pumilus and B. subtilis) are among those containing strains considered to be
      foodborne pathogens and nine of the isolated non-Bacillales bacterial species
      have been reported to contain human opportunistic pathogenic strains.

PMID- 29173632
TI  - Microbiological, chemical and sensory spoilage analysis of raw Atlantic cod
      (Gadus morhua) stored under modified atmospheres.
AB  - During fish spoilage, microbial metabolism leads to the production of volatile
      organic compounds (VOCs), characteristic off-odors and eventual consumer
      rejection. The aim of the present study was to contribute to the development of
      intelligent packaging technologies by identifying and quantifying VOCs that
      indicate spoilage of raw Atlantic cod (Gadus morhua) under atmospheres (%v/v
      CO2/O2/N2) 60/40/0, 60/5/35 and air. Spoilage was examined by microbiological,
      chemical and sensory analyses over storage time at 4 or 8  degrees C. Selected
      ion flow-tube mass spectrometry (SIFT-MS) was used for quantifying selected VOCs
      and amplicon sequencing of the 16S rRNA gene was used for the characterization of
      the cod microbiota. OTUs classified within the Photobacterium genus increased in
      relative abundance over time under all storage conditions, suggesting that
      Photobacterium contributed to spoilage and VOC production. The onset of
      exponential VOC concentration increase and sensory rejection occurred at high
      total plate counts (7-7.5 log). Monitoring of early spoilage thus calls for
      sensitivity for low VOC concentrations.

PMID- 29173633
TI  - Virgin olive oil yeasts: A review.
AB  - This review summarizes current knowledge on virgin olive oil yeasts. Newly
      produced olive oil contains solid particles and micro drops of vegetation water
      in which yeasts reproduce to become the typical microbiota of olive oil. To date,
      about seventeen yeast species have been isolated from different types of olive
      oils and their by-products, of which six species have been identified as new
      species. Certain yeast species contribute greatly to improving the sensorial
      characteristics of the newly produced olive oil, whereas other species are
      considered harmful as they can damage the oil quality through the production of
      unpleasant flavors and triacylglycerol hydrolysis. Studies carried out in certain
      yeast strains have demonstrated the presence of defects in olive oil treated with
      Candida adriatica, Nakazawaea wickerhamii and Candida diddensiae specific
      strains, while other olive oil samples treated with other Candida diddensiae
      strains were defect-free after four months of storage and categorized as extra
      virgin. A new acetic acid producing yeast species, namely, Brettanomyces
      acidodurans sp. nov., which was recently isolated from olive oil, could be
      implicated in the wine-vinegary defect of the product. Other aspects related to
      the activity of the lipase-producing yeasts and the survival of the yeast species
      in the flavored olive oils are also discussed.

PMID- 29173634
TI  - Influence of surface polysaccharides of Escherichia coli O157:H7 on plant defense
      response and survival of the human enteric pathogen on Arabidopsis thaliana and
      lettuce (Lactuca sativa).
AB  - This study aimed to determine the influence of bacterial surface polysaccharides
      (cellulose, colanic acid, and lipopolysaccharide; LPS) on the colonization or
      survival of Escherichia coli O157:H7 on plants and the plant defense response.
      Survival of E. coli O157:H7 were evaluated on Arabidopsis thaliana and romaine
      lettuce as a model plant and an edible crop (leafy vegetable), respectively. The
      population of the wild-type strain of E. coli O157:H7 on Arabidopsis plants and
      lettuce was significantly (P < 0.05) greater compared with the colanic acid
      deficient and LPS-truncated mutants on day 1 and day 5 post-inoculation. This
      result indicates that colanic acid and LPS structures may contribute to the
      ability of bacterial survival or persistence on plants. The wild-type strain of
      E. coli O157:H7 produced approximately twice the amount (P < 0.05) of capsular
      polysaccharide (CPS) than the colanic acid and LPS-truncated mutants. The
      significantly lower production of CPS was associated with significantly greater
      (2-fold) expression of pathogenesis-related gene (PR1) compared with the wild
      type and cellulose-deficient mutant (P < 0.05). Collectively, the results of this
      study may suggest that specific surface polysaccharides of E. coli O157:H7
      differentially induce the plant defense response, consequently affecting the
      survival of the human pathogen on plants. The survival and persistence of E. coli
      O157:H7 was similar on Arabidopsis and lettuce regardless of day post
      inoculation.

PMID- 29173635
TI  - Appropriate vacuolar acidification in Saccharomyces cerevisiae is associated with
      efficient high sugar fermentation.
AB  - Vacuolar acidification serves as a homeostatic mechanism to regulate
      intracellular pH, ion and chemical balance, as well as trafficking and recycling
      of proteins and nutrients, critical for normal cellular function. This study
      reports on the importance of vacuole acidification during wine-like fermentation.
      Ninety-three mutants (homozygous deletions in lab yeast strain, BY4743), which
      result in protracted fermentation when grown in a chemically defined grape juice
      with 200 g L-1 sugar (pH 3.5), were examined to determine whether fermentation
      protraction was in part due to a dysfunction in vacuolar acidification (VA)
      during the early stages of fermentation, and whether VA was responsive to the
      initial sugar concentration in the medium. Cells after 24 h growth were dual
      labelled with propidium iodide and vacuolar specific probe 6-carboxyfluorescein
      diacetate (6-CFDA) and examined with a FACS analyser for viability and impaired
      VA, respectively. Twenty mutants showed a greater than two-fold increase in
      fluorescence intensity; the experimental indicator for vacuolar dysfunction; 10
      of which have not been previously annotated to this process. With the exception
      of Deltahog1, Deltapbs2 and Deltavph1 mutants, where dysfunction was directly
      related to osmolality; the remainder exhibited increased CF-fluorescence,
      independent of sugar concentration at 20 g L-1 or 200 g L-1. These findings offer
      insight to the importance of VA to cell growth in high sugar media.

PMID- 29173636
TI  - Development of a PCR-RFLP method based on the transcription elongation factor 1
      alpha gene to differentiate Fusarium graminearum from other species within the
      Fusarium graminearum species complex.
AB  - Fusarium head blight (FHB) is a destructive disease of cereals crops worldwide
      and a major food safety concern due to grain contamination with trichothecenes
      and other mycotoxins. Fusarium graminearum, a member of the Fusarium graminearum
      species complex (FGSC) is the dominant FHB pathogen in many parts of the world.
      However, a number of other Fusarium species, including other members of the FGSC,
      may also be present for example in Argentina, New Zealand, Ethiopia, Nepal,
      Unites States in cereals such as wheat and barley. Proper species identification
      is critical to research aimed at improving disease and mycotoxin control
      programs. Identification of Fusarium species is are often unreliable by
      traditional, as many species are morphologically cryptic. DNA sequence-based
      methods offer a reliable means of species identification, but can be expensive
      when applied to the analyses of population samples. To facilitate identification
      of the major causative agent of FHB, this work describes an easy and inexpensive
      method to differentiate F. graminearum from the remaining species within the FGSC
      and from the other common Fusarium species causing FHB in cereals. The developed
      method is based on a PCR-RFLP of the transcription elongation factor (TEF 1
      alpha) gene using the restriction enzyme BsaHI.

PMID- 29173638
TI  - Detection and identification of Penicillium spp. in a frozen chicken nuggets
      production facility.
AB  - Frozen chicken nuggets can be stored over a long period, during which time they
      may be exposed to temperature abuse conditions leading to spoilage by
      psychrophilic filamentous fungi. The purpose of this study was to investigate the
      main sources of chicken nugget spoilage. Mycological analyses were performed
      using raw materials and products from each stage of processing, as well as from
      the industry's indoor air environment. The species were identified through
      observation of macroscopic and microscopic characteristics of isolates. The
      powder coating of samples showed counts between 101 and 104 CFU/g, predominantly
      of the species Penicillium polonicum, Aspergillus flavus, Aspergillus candidus,
      Aspergillus (Eurotium) amstelodami and Penicillium citrinum. During chicken
      nugget processing, a reduction in fungal counts to 101 CFU/g was observed, with
      P. polonicum as the most dominant species present. Penicillium glabrum was the
      only species isolated from the final product analyzed (10%). Additionally, it was
      also the predominant species in the factory's air environment. According to the
      results, two possible sources of contamination of frozen chicken nuggets were
      detected, one from the lack of quality of the powder coatings used and another
      from the lack of clean air from the factory environment between the stages of
      baking and packaging.

PMID- 29173637
TI  - Screening of adjunct cultures and their application in ester formation in
      Camembert-type cheese.
AB  - The ethanol content and esterase and alcohol acyltransferase activities are the
      limiting factors in the synthesis of ethyl esters in Camembert-type cheeses. This
      study aimed to investigate the effects of alcohol, esterase and alcohol
      acyltransferase activities on ethyl ester formation in Camembert-type cheeses.
      Five experimental cheeses were prepared with three adjunct cultures with
      different enzyme activities and two levels of ethanol content (400 or 800 MUg/g).
      The cheeses were aged for 4 weeks and analysed weekly for basic physicochemical,
      textural, volatile and sensory properties. The results showed that both the
      enzyme activity and ethanol content were limiting factors in the synthesis of
      ethyl esters in the Camembert-type cheeses. Variation in the esterase synthesis
      activity was observed among lactic acid bacteria, and the starter culture
      Lactococcus lactis MA 14 LYO distinguished itself through its high acidifying and
      esterase hydrolysis abilities. The addition of CCFM 12, a lactic acid bacteria
      strain with high esterase and alcohol acyltransferase activity, along with 400 or
      800 MUg/g of ethanol, notably enhanced the generation of ethyl esters and the
      corresponding fruity flavour, without causing dramatic changes in the basic
      physicochemical indices and microbial profile. In addition, cohesiveness was
      influenced by the addition of 400 and 800 MUg/g of ethanol, and more resilience
      with 800 MUg/g of ethanol had been found. The results showed that the addition of
      CCFM12 with 400 and 800 MUg/g of ethanol may be applied in the production of
      Camembert cheese to enhance its fruity flavour.

PMID- 29173639
TI  - Escherichia coli and Cronobacter sakazakii in 'Tommy Atkins' minimally processed
      mangos: Survival, growth and effect of UV-C and electrolyzed water.
AB  - These studies were aimed at assessing the growing capacity of Escherichia coli
      and Cronobacter sakazakii and the effectiveness of Ultraviolet-C (UV-C)
      radiation, acidic electrolyzed (AEW) and neutral electrolyzed (NEW) waters in the
      inhibition of these bacteria on minimally processed 'Tommy Atkins' mangoes (MPM).
      The fruits were contaminated by dip inoculation and kept 10 days at 4, 8, 12 and
      20  degrees C while enumerating bacteria. Contaminated mangoes were disinfected
      using UV-C (2.5, 5, 7.5 and 10 kJ/m2), AEW, NEW and sodium hypochlorite (SH) and
      the microorganisms were monitored. None of the enterobacteria grew at 4, 8 and 12
      degrees C regardless of having persisted during the 10-day period. At 20 
      degrees C, E. coli and C. sakazakii grew, after adaption phases of 48 h and 24 h,
      to values of 8.7 and 8.5 log cfu/g at day eight, respectively. E. coli showed the
      highest reduction counts on the MPM washed with NEW and SH (2.2 log cfu/g). UV-C
      was more effective in reducing C. sakazakii (2.4-2.6 log cfu/g), when compared to
      AEW, NEW and SH (1.2-1.8 log cfu/g). The efficacy of decontamination technologies
      depends on microorganisms, highlighting the importance of preventing
      contamination at the primary production and of combining different methods to
      increase the safety of fresh-cut fruits.

PMID- 29173640
TI  - Effect of high pressure processing on the survival of Salmonella Enteritidis and
      shelf-life of chicken fillets.
AB  - High pressure processing (HPP) is a preservation technology alternative to heat
      treatment that is mild for food, but effectively inactivates the spoilage
      microbiota and foodborne pathogens of several foods. The purpose of the current
      study was to evaluate the effect of HPP on Salmonella ser. Enteritidis,
      indigenous microbiota and shelf-life of chicken fillets. Chicken fillets were
      inoculated with S. Enteritidis at three different initial inocula (3, 5, 7 log
      CFU/g), packed under vacuum, treated or not with HPP (500 MPa/10 min) and stored
      at 4 and 12  degrees C. Total viable counts, S. Enteritidis, pseudomonads,
      Brochothrix thermosphacta, lactic acid bacteria, Enterobacteriaceae and
      yeasts/molds populations were determined in parallel with sensory analysis of non
      inoculated samples. The HPP resulted in the reduction of the pathogen population
      below the detection limit of the enumeration method (0.48 log CFU/g),
      irrespective of the inoculum. During the shelf life of the HPP samples, the
      pathogens population remained below or near the detection limit of the
      enumeration method at both temperatures, except from the high inoculum case that
      an increase was observed at 12  degrees C. At the low inoculum level, the
      pathogen could not be detected with the enrichment method after the first storage
      days (2nd day for 4  degrees C and 0 day for 12  degrees C). The survival of
      Salmonella strains was assessed by pulsed field gel electrophoresis and it was
      shown that the survival of the different strains depended on the inoculum and
      storage temperature. Regarding the indigenous microbiota, Br. thermosphacta was
      reported for the first time to be the main spoilage microorganism that survived
      and dominated after the HPP. From the results it was evident that, HPP may
      enhance the safety and increase the shelf life (6 at 4  degrees C and 2 days at
      12  degrees C) of chicken meat.

PMID- 29173641
TI  - Microbial biodiversity of Sardinian oleic ecosystems.
AB  - The olives are rich in microorganisms that, during the extraction process may
      persist in the oils and can influence their physicochemical and sensory
      characteristics. In this work, and for the first time, we isolated and identified
      microbial species, yeast and bacteria, present during the production process in
      four Sardinian (Italy) oleic ecosystems. Among these varieties, we found that
      Nera di Gonnos was associated to the highest microbial biodiversity, which was
      followed by Bosana, Nocellara del Belice and Semidana. Among the different
      microbial species isolated, some are specific of olive ecological niches, such as
      Cryptococcus spp and Serratia spp; and others to olive oils such as Candida spp
      and Saccharomyces. Some other species identified in this work were not found
      before in oleic ecosystems. The enzymatic analyses of yeast and bacteria showed
      that they have good beta-glucosidase activity and yeast also showed good beta
      glucanase activity. The majority of bacteria presented lipolytic and catalase
      activities while in yeast were species-specific. Interestingly, yeast and
      bacteria isolates presented a high resistance to bile acid, and about 65% of the
      yeast were able to resist at pH 2.5 for 2 h. Finally, bacteria showed no biofilm
      activity compared to yeast.

PMID- 29173642
TI  - Diversity of bacterial communities in French chicken cuts stored under modified
      atmosphere packaging.
AB  - Poultry meat, the second most consumed meat in France, is commercialized mainly
      as portions of chicken cuts with various quality labels, stored under various
      modified atmosphere packaging (MAP), with shelf-life ranging from 9 to 17 days.
      We used 16S rDNA pyrosequencing to describe microbiota of chicken legs. Ten
      samples representing a wide diversity of labels and MAP available on the market
      were collected from local supermarkets and stored at 4  degrees C. Microbiota
      were collected, total DNA was extracted, and V1-V3 fragment of 16S rRNA genes
      were amplified and sequenced. For data analysis several pipelines were compared.
      The Qiime pipeline was chosen to cluster reads and we used a database previously
      developed for a meat and fish microbial ecology study. Variability between
      samples was observed and a listing of bacteria present on chicken meat was
      established. The structure of the bacterial communities were compared with
      traditional cultural methods and validated with quantitative real time PCR.
      Brochothrix thermosphacta, Pseudomonas sp., and Carnobacterium sp. were dominant
      and the nature of the gas used for packaging influenced the relative abundance of
      each suggesting a MAP gas composition dependent competition between these
      species. We also noticed that slaughterhouse environment may influence the nature
      of the contaminants.

PMID- 29173643
TI  - Primary souring: A novel bacteria-free method for sour beer production.
AB  - In the beverage fermentation industry, especially at the craft or micro level,
      there is a movement to incorporate as many local ingredients as possible to both
      capture terroir and stimulate local economies. In the case of craft beer, this
      has traditionally only encompassed locally sourced barley, hops, and other
      agricultural adjuncts. The identification and use of novel yeasts in brewing lags
      behind. We sought to bridge this gap by bio-prospecting for wild yeasts, with a
      focus on the American Midwest. We isolated 284 different strains from 54 species
      of yeast and have begun to determine their fermentation characteristics. During
      this work, we found several isolates of five species that produce lactic acid and
      ethanol during wort fermentation: Hanseniaspora vineae, Lachancea fermentati,
      Lachancea thermotolerans, Schizosaccharomyces japonicus, and Wickerhamomyces
      anomalus. Tested representatives of these species yielded excellent attenuation,
      lactic acid production, and sensory characteristics, positioning them as viable
      alternatives to lactic acid bacteria (LAB) for the production of sour beers.
      Indeed, we suggest a new LAB-free paradigm for sour beer production that we term
      "primary souring" because the lactic acid production and resultant pH decrease
      occurs during primary fermentation, as opposed to kettle souring or souring via
      mixed culture fermentation.

PMID- 29173644
TI  - Seafood pathogens and information on antimicrobial resistance: A review.
AB  - Seafood-borne diseases are a major public health hazard in the United States and
      worldwide. Per capita, seafood consumption has increased globally during recent
      decades. Seafood importation and domestic aquaculture farming has also increased.
      Moreover, several recent outbreaks of human gastroenteritis have been linked to
      the consumption of contaminated seafood. Investigation of seafood-borne illnesses
      caused by norovirus, and Vibrio, and other bacteria and viruses require a
      concrete knowledge about the pathogenicity and virulence properties of the
      etiologic agents. This review explores pathogens that have been associated with
      seafood and resulting outbreaks in the U.S. and other countries as well as the
      presence of antimicrobial resistance in the reviewed pathogens. The spectrum of
      such resistance is widening due to the overuse, misuse, and sub-therapeutic
      application of antimicrobials in humans and animals.

PMID- 29173645
TI  - Different Lactobacillus populations dominate in "Chorizo de Leon" manufacturing
      performed in different production plants.
AB  - "Chorizo de Leon" is a high-value Spanish dry fermented sausage traditionally
      manufactured without the use of starter cultures, owing to the activity of a
      house-specific autochthonous microbiota that naturally contaminates the meat from
      the environment, the equipment and the raw materials. Lactic acid bacteria
      (particularly Lactobacillus) and coagulase-negative cocci (mainly Staphylococcus)
      have been reported as the most important bacterial groups regarding the
      organoleptic and safety properties of the dry fermented sausages. In this study,
      samples from raw minced meat to final products were taken from five different
      producers and the microbial diversity was investigated by high-throughput
      sequencing of 16S rRNA gene amplicons. The diverse microbial composition observed
      during the first stages of "Chorizo de Leon" evolved during ripening to a
      microbiota mainly composed by Lactobacillus in the final product. Oligotyping
      performed on 16S rRNA gene sequences of Lactobacillus and Staphylococcus
      populations revealed sub-genus level diversity within the different
      manufacturers, likely responsible of the characteristic organoleptic properties
      of the products from different companies.

PMID- 29173646
TI  - Schisandra chinensis berry extract protects against steatosis by inhibiting
      histone acetylation in oleic acid-treated HepG2 cells and in the livers of diet
      induced obese mice.
AB  - We hypothesized that hepatic steatosis could be mitigated by the hypolipidemic
      activity of Schisandra chinensis berry ethanol extract (SCE) via the inhibition
      of histone acetyltransferase (HAT) activity. HepG2 cells treated with oleic acid
      (OA) in the presence of SCE exhibited reduced OA-induced lipid accumulation,
      which was likely mediated by reductions in SREBP-1c expression. SCE attenuated
      the acetylation of total lysine and H3K9 that was otherwise increased by OA. Male
      obese mice fed with either a low-fat diet or Western diet exhibited reduced body
      and liver weights when supplemented with 1% SCE. The SCE-mediated attenuation of
      hepatic lipid accumulation was accompanied by a decrease in the expression of
      lipogenic genes. SCE also attenuated the expression of acetylated lysine and non
      acetylated forms of H3K9 acetylation in the livers of these mice. Taken together,
      these results suggest that SCE has potential for further development as a novel
      therapeutic agent for the prevention of steatosis.

PMID- 29173647
TI  - Diet-induced obesity and weight loss alter bile acid concentrations and bile acid
      sensitive gene expression in insulin target tissues of C57BL/6J mice.
AB  - Bile acids (BAs) influence the metabolism of glucose, lipids, and energy
      expenditure. We hypothesized that BA concentrations and related gene expression
      would be altered in lean (low-fat diet fed; LFD) vs diet-induced obese (high-fat
      diet fed; HFD) groups of mice and that some detected changes would remain after
      weight loss in an HFD group switched to the LFD (SW). Taurine conjugates
      dominated the bile acid composition of the liver, epididymal white adipose tissue
      (eWAT), and hypothalamus, with the latter having lower levels (~95%, ~95%, and
      ~80%, respectively; P<.05). Plasma conjugated bile acids were elevated in the HFD
      relative to the LFD and SW animals. Total hepatic BA concentrations decreased in
      obese mice fed HFD, and levels returned to preobese levels in the SW group.
      Subtle changes in unconjugated bile acids were detected in the eWAT,
      hypothalamus, and muscle. Liver expression of a variety of enzymes involved in BA
      synthesis (eg, Cyp27a1, Acox2), BA transport (eg, Slc22a8), and BA-sensitive
      receptors (Fxr, Tgr5) were unchanged by HFD feeding but decreased with SW. Other
      hepatic enzymes were induced in the SW group (eg, Amacr and Bal). In eWAT,
      Cyp27a1 and Acox2 also declined in the SW group, whereas the HFD group showed
      reduced expression of BA transporters (eg, Abcc3), and changes in Fxr and Tgr5
      were unclear. Therefore, although most detectable changes in BA metabolism
      associated with diet-induced obesity are reversed by diet-induced weight loss,
      some effects on BA composition, concentrations, and gene expression can persist
      after weight loss.

PMID- 29173648
TI  - In silico identification of milk antihypertensive di- and tripeptides involved in
      angiotensin I-converting enzyme inhibitory activity.
AB  - Identification of bioactive milk peptides could improve food technology through
      improved selection of food supplements with a focus on antihypertensive
      properties. We hypothesized that angiotensin I-converting enzyme (ACE) inhibitory
      activities of milk di- and tripeptides could be predicted using 3-dimensional
      quantitative structure activity relationship methods and that these activities
      could be explained through evaluation of structural features (hydrogen bond
      donor/acceptor, hydrophobic, steric, and electrostatic) that are responsible for
      this bioactivity. We aimed to build comparative molecular field analysis (CoMFA)
      models combined with in silico digestion to predict the peptide sequences
      released from enzymatic digestion and to evaluate peptides without experimental
      data. Furthermore, molecular docking simulation was performed with the aim to
      evaluate structural features. Molecular docking simulations revealed that the
      most potent inhibitory peptides contain hydrophobic amino acids that enter deep
      into the hydrophobic pocket of the ACE active site and make interactions with its
      residues. CoMFA results point out favorable steric interactions and
      electronegativity at the C-terminus of the milk dipeptides. The CoMFA model
      appears to favor electropositive amino acids at the second place in tripeptides
      and electronegative interaction with Tyr520. Furthermore, predicted values of ACE
      inhibitory activity of dipeptides obtained by peptide cutter are relatively high,
      which recommend them for application as functional food supplements and natural
      alternatives to ACE inhibitory drugs. This research suggests that obtained 3
      dimensional quantitative structure activity relationship models are able to
      successfully identify milk-derived di- and tripeptides that have significant
      antihypertensive activity and provide information for screening and design of
      novel ACE inhibitors that could be used as supplements in human nutrition.

PMID- 29173649
TI  - An obesogenic diet enriched with blue mussels protects against weight gain and
      lowers cholesterol levels in C57BL/6 mice.
AB  - Obesity is linked to several health complications, such as cardiovascular
      disease, insulin resistance, and hypertension. Dyslipidemia in obesity is one of
      the prime causes for health complications. We have previously shown that blue
      mussels (BM) are a rich source of omega (n)-3 polyunsaturated fatty acids (PUFA)
      and increase the mRNA expression of peroxisome-proliferator activated receptor
      and adiponectin, thereby inducing anti-obesity and insulin sensitizing effects in
      vitro. However, the in vivo effects of BM on obesity and metabolic regulation are
      not known. We hypothesized that dietary intake of BM will prevent weight gain and
      improve lipid profile of C57BL/6 mice fed a high-fat diet (HFD). Mice were fed a
      HFD supplemented with 5% w/w BM (BM-HFD) for 4 weeks, and then switched to a HFD
      for 4 weeks. Mice fed a BM-HFD showed significantly lower body weight gain and
      abdominal fat, compared to the HFD. Furthermore, a BM-HFD significantly reduced
      plasma and hepatic total and low-density lipoprotein (LDL)-cholesterol, compared
      to HFD. The decrease in cholesterol levels coincided with inhibition of hepatic
      sterol regulatory element-binding protein-2 and HMG-CoA reductase mRNA
      expression, and an increase in LDL-receptor gene expression in the BM-HFD group,
      compared to the HFD group. In conclusion, our findings have established that BM
      reduces body weight gain in mice. BM may have potential to lower cholesterol
      levels by inhibiting cholesterol synthesis, thereby protecting against obesity
      and perhaps heart disease.

PMID- 29173650
TI  - Evidence for the effectiveness of pomegranate supplementation for blood pressure
      management is weak: A systematic review of randomized clinical trials.
AB  - Hypertension is one of the most important preventable causes of premature death.
      Studies have been conducted assessing the impact of pomegranate on blood
      pressure, with varying results. The aim of this review was to critically appraise
      and evaluate the effect of pomegranate on blood pressure in adults, using
      evidence from randomized clinical trials (RCTs). We conducted electronic searches
      in Medline, Embase, Amed, and The Cochrane Library, and included RCTs assessing
      the effectiveness of pomegranate on blood pressure. We assessed the reporting
      quality using the Cochrane criteria. We included 8 RCTs comprising 619
      participants. The studies varied in their reporting quality, and compared
      pomegranate juice or capsules with a control. Two studies reported significant
      reductions in systolic blood pressure favoring pomegranate: p = .002 and p < .001
      respectively; 3 studies reported no significant differences between groups; and 3
      studies failed to report between-group differences. Two studies reported
      significant reductions in diastolic blood pressure favoring pomegranate: p =
      .038, p < .001, respectively; 4 studies reported no significant between-group
      differences; and 2 studies did not report between group differences. No adverse
      events were observed. The limited evidence from clinical trials to date fails to
      convincingly show a beneficial effect of pomegranate on blood pressure. We have
      identified evidence gaps and highlight areas for future research to be conducted,
      including performing studies of high quality and longer duration.

PMID- 29173651
TI  - Foreword.

PMID- 29173653
TI  - Cystic lesions of the liver-A review.

PMID- 29173654
TI  - Editorial: High Pressure Bioscience and Biotechnology.

PMID- 29173655
TI  - Management of Well-differentiated Gastroenteropancreatic Neuroendocrine Tumors
      (GEPNETs): A Review.
AB  - PURPOSE: Neuroendocrine tumors (NETs) are heterogeneous tumors that arise from
      the neuroendocrine cells of the digestive tract and other organs, such as the
      lung, ovary, and thyroid glands. They can be well differentiated or poorly
      differentiated, and management of these tumors differs for each histologic
      subtype. We have performed a review of NETs and focused on management of well
      differentiated gastroenteropancreatic neuroendocrine tumors (GEPNETs) and
      carcinoid syndrome. METHODS: A PubMed search was performed to obtain articles on
      the management of well-differentiated NETs. Using the key words neuroendocrine
      tumors, carcinoid, pNET, octreotide, somatostatin analogues, and radiolabeled
      therapy, we reviewed Phase II and III trials that were published over the past 30
      years. We also reviewed guidelines from the European Neuroendocrine Tumor
      Society, North America Neuroendocrine Tumor Society, and National Comprehensive
      Cancer Network in our search. FINDINGS: NETs are usually slow-growing tumors that
      remain asymptomatic for a long duration and can be either nonfunctioning or
      functioning. Surgical resection is recommended for locoregional disease,
      impending obstruction, symptom control, and advanced disease. Nonsurgical
      treatment options include somatostatin analogues (SSAs), multikinase inhibitors,
      targeted therapy, chemotherapy, and radiolabeled SSAs. Carcinoid syndrome is
      mainly treated with SSAs. IMPLICATIONS: Although GEPNETs are slow-growing tumors,
      most patients are diagnosed with metastatic disease, and therefore it is
      important that the management of each patient be discussed in a multidisciplinary
      setting to optimize the treatment strategy. Patients should be considered for
      clinical trials and refractory cases referred to a specialty center.

PMID- 29173656
TI  - Cervical Epidural Steroid Injection: Techniques and Evidence.
AB  - Cervical epidural steroid injections are a common treatment of cervical radicular
      pain. Important safety considerations include attention to the possibility of
      spinal cord infarction and spinal epidural hematoma. When appropriate,
      radiographic, technical, and pharmacologic principals are used, these procedures
      are relatively safe. Cervical epidural steroid injections are effective for the
      short-term treatment of radicular pain. More rigorously designed clinical
      outcomes studies of both cervical interlaminar and transforaminal epidural
      steroid injections are needed.

PMID- 29173657
TI  - Sonographic Guide for Botulinum Toxin Injections of the Neck Muscles in Cervical
      Dystonia.
AB  - Intramuscular botulinum toxin (BoTX) injection is the first-line treatment of
      cervical dystonia. Poor treatment outcomes and some side effects, however, have
      been reported after BoTX applications. One of the most important reasons is
      incorrect localization of the needle during toxin injections. Without imaging, it
      is impossible to verify precise needle positioning in the proper muscle.
      Ultrasound has been recommended because of its high capability in illustrating
      most of the neck muscles. This review article discusses how ultrasound imaging
      can be used to scan/access neck muscles, mainly from the perspective of BoTX
      injections.

PMID- 29173658
TI  - Prolotherapy for the Thoracolumbar Myofascial System.
AB  - Prolotherapy has focused on entheses as a key source of chronic low back pain,
      even without clear diagnosis of enthesopathy. Treatment has traditionally been
      guided by anatomic knowledge and careful palpation. This article integrates
      ultrasonographic diagnosis of fascial injury with examination findings taught in
      traditional prolotherapy technique. Thoracolumbar fascial anatomy and
      biotensegrity theory are used to explain patient presentation and response to
      treatment at these pathologic findings. Detailed case reports provide proof of
      concept for the 60-year history of prolotherapy in the treatment of chronic low
      back pain.

PMID- 29173659
TI  - Radiofrequency Denervation of the Cervical and Lumbar Spine.
AB  - Facet or zygapophysial joint pain is commonly seen in the aging population.
      Interventional procedures, such as facet joint nerve blocks, facet intraarticular
      injections, and radiofrequency denervation, are used for the diagnosis and
      treatment of axial spinal chronic neck and low back pain. The focus of this
      article is to understand how radiofrequency denervation works in the cervical and
      lumbar spine and to be able to properly select appropriate patients who might
      benefit from this safe and effective procedure.

PMID- 29173660
TI  - Safety and Complications of Cervical Epidural Steroid Injections.
AB  - Serious neurologic complications following cervical transforaminal epidural
      steroid injections (CTFESI) and cervical interlaminar epidural steroid injections
      (CILESI) have been reported. For CILESI, this is caused by aberrant needle
      placement or space-occupying lesions, such as hematoma or abscess. For CTFESI,
      this is caused by embolic infarct when inadvertent intra-arterial injection of
      particulate steroids has occurred. Multiple safety techniques are used to
      mitigate the risk of these serious complications. The most common adverse events
      that occur following CTFESI or CILESI are procedural-related pain, steroid side
      effects, and vasovagal reactions, which are relatively minor and self-limited.

PMID- 29173661
TI  - Sacroiliac Joint Interventions.
AB  - Sacroiliac joint (SIJ) pain is an important cause of lower back problems.
      Multiple SIJ injection techniques have been proposed over the years to help in
      the diagnosis and treatment of this condition. However, the SIJ innervation is
      complex and variable, and truly intra-articular injections are sometimes
      difficult to obtain. Different sacroiliac joint injections have shown to provide
      pain relief in patients suffering this ailment. Various techniques for
      intraarticular injections, sacral branch blocks and radiofrequency ablation, both
      fluoroscopy guided and ultrasound guided are discussed in this paper. Less common
      techniques like prolotherapy, platelet rich plasma injections and botulism toxin
      injections are also discussed.

PMID- 29173662
TI  - Image and Contrast Flow Pattern Interpretation for Attempted Epidural Steroid
      Injections.
AB  - Fluoroscopically guided, contrast-enhanced epidural steroid injections (ESIs) are
      frequently performed for radicular symptoms. Interventionalists performing these
      procedures should have a thorough and detailed understanding of spinal anatomy to
      safely and effectively deliver the desired injectate to the targeted site. Being
      able to differentiate epidural from nonepidural contrast flow is vital as is
      recognizing flow to undesired locations. This article summarizes the
      characteristics that distinguish between ideal epidural flow patterns and
      nonideal subarachnoid, intradural, and other suboptimal contrast flow patterns.
      Recognizing these patterns is essential for safe and successful ESIs and to
      prevent avoidable complications.

PMID- 29173663
TI  - Lumbosacral Transitional Segments: An Interventional Spine Specialist's Practical
      Approach.
AB  - The presence of a lumbosacral transitional vertebrae (LSTV) should prompt a more
      detailed preprocedural evaluation of the vertebral column to accurately determine
      spinal levels. An LSTV should prompt the use of corroborating intraprocedural
      imaging to verify morphology. The most important factors in treating lumbosacral
      transitional segments are communication among treating physicians to ensure
      segmental enumeration consistency and associated appropriate patient treatment.

PMID- 29173664
TI  - Ultrasound for Lumbar Spinal Procedures.
AB  - Ultrasonography has become an increasingly valuable and promising tool for
      performing image-guided spine interventions. The increase in the use of
      ultrasound utilization has led to more studies evaluating ultrasound-guided
      interventional spine procedures in comparison to fluoroscopy and computed
      tomography. Several studies have investigated the use of ultrasound for
      lumbosacral pain management procedures with favorable outcomes.

PMID- 29173665
TI  - Peripheral Nerve Radiofrequency Neurotomy: Hip and Knee Joints.
AB  - Intra-articular hip and knee pain is a common cause of physical and psychosocial
      disability. Many conservative treatment options provide only short-term relief.
      Recent research studies have shown improvement in pain and function with minimal
      complications after radiofrequency neurotomy of the hip and the knee, especially
      in patients who have failed conservative treatment or are not surgical
      candidates. More quality research studies are needed to establish the efficacy
      and safety of these procedures in patients with refractory hip and knee pain.

PMID- 29173666
TI  - Lumbar Epidural Steroid Injections.
AB  - Lumbar epidural steroid injections under fluoroscopic guidance are used very
      commonly for the treatment of low back and lower extremity radicular pain. These
      procedures have been shown to be effective for pain relief in the short term and
      are relatively safe. The indications, evidence, and safety considerations for 2
      different techniques-namely, interlaminar and transforaminal-are discussed.

PMID- 29173667
TI  - Ultrasound-Guided Interventions of the Cervical Spine and Nerves.
AB  - High-resolution ultrasound (US) enables prompt depiction of muscles, tendons,
      ligaments, and peripheral nerves. It seems to be the best imaging modality for
      guiding perineural injections. The most complicated neurovascular network of the
      musculoskeletal system surrounds the cervical spine; so injection to that region
      is never an easy task. This article elaborates the regional anatomy and the use
      of US scanning and guidance for cervical interventions; for example, cervical
      root, superficial cervical plexus, stellate ganglion, cervical medial branch,
      greater occipital nerve, and third occipital nerve. The article aims to lead
      readers to practice US-guided cervical injections precisely and safely.

PMID- 29173668
TI  - Foreword.

PMID- 29173669
TI  - Preface.

PMID- 29173670
TI  - Evaluation of Chest Pain and Acute Coronary Syndromes.
AB  - Chest pain is a common complaint in the emergency department, and it is the job
      of clinicians to rule out life-threatening diagnoses such as acute coronary
      syndrome. The history, physical examination, cardiac risk factors,
      electrocardiogram findings, and clinician judgment are often not enough to
      distinguish between causes of chest pain syndromes and to reliably rule out acute
      myocardial ischemia. New cardiac troponin assays, especially in conjunction with
      clinical decision algorithms, help clinicians rapidly exclude acute myocardial
      infarction. For further risk stratification, stress testing or coronary computed
      tomography angiography can be used in the emergency department.

PMID- 29173671
TI  - Acute Myopericardial Syndromes.
AB  - Acute myopericardial syndromes are common but can be challenging to manage and
      potentially have life-threatening complications. Careful clinical history,
      physical examination, electrocardiogram interpretation, and application of
      diagnostic criteria are needed to make an accurate diagnosis, exclude concomitant
      disease, and properly treat patients. Therapy for acute pericarditis should be
      guided per the underlying cause. For the most common causes, nonsteroidal
      antiinflammatory drugs or aspirin with the addition of colchicine remains the
      mainstay of therapy. Patients with hemodynamic compromise who are resistant to
      therapy or display high-risk features should prompt hospitalization and
      initiation of more aggressive and/or invasive therapy.

PMID- 29173672
TI  - Acute Valvular Heart Disease.
AB  - Valvular heart disease (VHD) is a common clinical entity. Recognition of
      decompensated VHD is crucial to instituting appropriate workup and management.
      Initial evaluation focuses on hemodynamics, peripheral perfusion, volume
      overload, and active myocardial ischemia. Initial therapy is targeted at
      improving hemodynamics, fluid status, and decreasing myocardial ischemia before
      intervention. Echocardiography can rapidly identify VHD etiology and severity
      along with physical examination findings. Owing to improved survival with cardiac
      surgery over the past several decades, prosthetic valve dysfunction should be
      recognized and initial treatment understood. Mechanical circulatory support is
      increasingly part of clinical practice in stabilizing patients with decompensated
      VHD.

PMID- 29173673
TI  - Ventricular Arrhythmias.
AB  - Ventricular tachycardia (VT) is the most common form of wide complex tachycardia
      and is associated with a high mortality rate. Electrocardiographic analysis
      remains paramount in diagnosis and helps to direct therapy. Antiarrhythmic
      agents, although effective in reducing arrhythmia burden, have never demonstrated
      a mortality benefit. The implantable cardioverter-defibrillator aids not only in
      the acute termination of ventricular arrhythmia, but provides a wealth of
      information for the long-term management of patients with VT. Contemporary
      treatment options such as catheter ablation are increasingly used and effective,
      but often remain imperfect, with recurrent VT being not uncommon.

PMID- 29173674
TI  - Evolving Electrocardiographic Indications for Emergent Reperfusion.
AB  - Chest pain or other symptoms concerning for acute coronary syndrome continues to
      remain a major reason for presentation to the emergency department. However,
      there is significant heterogeneity in the spectrum of risk severity of these
      patients. The electrocardiogram (ECG) remains a critically valuable tool in the
      physician's arsenal to diagnose patients and help with risk stratification. There
      are multiple high-risk ECG findings that are suggestive of adverse outcome and
      may benefit from rapid transfer for coronary angiography. This article reviews
      specific high-risk ECG patterns that may represent acute myocardial infarction or
      identify impending acute myocardial infarction that benefit from early diagnostic
      coronary angiography.

PMID- 29173675
TI  - Acute Management of Atrial Fibrillation: From Emergency Department to Cardiac
      Care Unit.
AB  - The prevalence of atrial fibrillation is increasing rapidly, resulting in more
      patients presenting for care in the emergency department and in-hospital
      settings. To reduce morbidity and mortality, and improve patient quality of life,
      clinicians working in these settings need to be both current and facile in their
      approach to management of these patients. Frequent updates to guideline
      recommendations (based on emerging research) make this challenging for practicing
      physicians. This article reviews the acute management of atrial fibrillation in
      the emergency and in-hospital settings, including practical approaches to rhythm
      and rate control, anticoagulation, and special situations, incorporating the most
      up-to-date guidelines.

PMID- 29173676
TI  - A New Face of Cardiac Emergencies: Human Immunodeficiency Virus-Related Cardiac
      Disease.
AB  - The human immunodeficiency virus epidemic is a major health challenge of the
      twenty-first century as the transition from infectious complications to
      noncommunicable disease becomes more evident. These patients may present to the
      emergency department with a variety of cardiovascular diseases, such as acute
      coronary syndromes, heart failure, pericardial disease, infective endocarditis,
      venothromboembolism, and other conditions. Increased awareness is needed among
      health care professionals to enhance adequate identification and promote prompt
      management of these patients.

PMID- 29173677
TI  - Cardiovascular Emergencies in Pregnancy.
AB  - Heart disease in pregnancy may manifest as acute coronary syndromes,
      decompensated valvular disease, and acute heart failure. These disease processes
      may represent progression of preexisting disease versus newly developed disease
      resulting from the physiologic changes of pregnancy. Early recognition of
      clinical presentations, judicious use of diagnostic studies, and
      multidisciplinary management of patient and fetal considerations can lead to
      optimal outcomes in this unique patient subset.

PMID- 29173678
TI  - Blunt Cardiac Trauma Review.
AB  - Patients suffering blunt cardiac trauma vary widely in the severity of their
      condition on presentation. Although some may present with mild sternal bruising,
      others may present with acute valvular rupture or malignant arrhythmia.
      Disposition for these patients ranges from discharge home to admission for urgent
      cardiac surgery. This article discusses some of the common types of blunt cardiac
      trauma and reviews the current literature and guidelines for their triage and
      initial management.

PMID- 29173679
TI  - Cardiac Biomarkers in Emergency Care.
AB  - This article critically reviews the latest evidence to guide the use of
      biomarkers for the diagnosis of acute coronary syndromes in practice. It shows
      how modern cardiac troponin assays can enable diagnoses to be ruled in or ruled
      out with a single blood test, with many more diagnoses confirmed or refuted in as
      little as 1 hour later. Finally, this article appraises the latest evidence for
      other cardiac biomarkers, such as heart-type fatty acid-binding protein and
      copeptin.

PMID- 29173680
TI  - Non-ST-Segment Acute Coronary Syndromes.
AB  - Acute coronary syndrome (ACS) represents an umbrella of ischemic myocardial
      disease and diagnoses encompassing unstable angina (UA), non-ST-elevation
      myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI).
      UA and NSTEMI for all intents and purposes, share similar pathophysiology, but at
      increasing severity. This article focuses on the diagnosis, risk stratification,
      management, and strategies that impact outcomes in NSTEMI.

PMID- 29173681
TI  - Cardiogenic Shock.
AB  - Cardiogenic shock (CS) is a physiologic state in which cardiac pump function is
      inadequate to perfuse the tissues. If CS is not rapidly recognized and treated,
      tissue hypoperfusion can quickly lead to organ dysfunction and patient death.
      Evaluation of patients with suspected CS should include an electrocardiogram,
      chest radiograph, laboratory studies, and bedside echocardiogram. Initial
      resuscitation is directed toward restoring cardiac output and tissue perfusion.
      Mechanical circulatory support is indicated for patients with CS who do not
      respond to pharmacologic therapy. Ultimately, these patients should undergo
      emergent reperfusion therapy with either percutaneous coronary intervention or
      coronary artery bypass grafting.

PMID- 29173682
TI  - Acute Dyspnea and Decompensated Heart Failure.
AB  - The majority of patients hospitalized with acute heart failure (AHF) initially
      present to the emergency department (ED). Correct diagnosis followed by prompt
      treatment ensures optimal outcomes. Paradoxically, identification of high risk is
      not the unmet need, given nearly all ED AHF patients are hospitalized; rather, it
      is identification of low-risk. Currently, no risk-stratification instrument can
      be universally recommended to safely discharge ED patients. With the exception of
      diagnosis, management recommendations are largely expert opinion, informed by
      existing evidence and tradition. In the absence of robust evidence, we propose a
      framework for management to guide the busy clinician.

PMID- 29173683
TI  - Evolving Strategies in Cardiac Arrest Management.
AB  - Cardiac arrest is a leading cause of death in the United States, with a hospital
      discharge rate of approximately 10%. International resuscitation guidelines offer
      standardized cardiac arrest management approaches, but beyond the guidelines, are
      promising innovations to improve resuscitative care. Although clinical data do
      not yet support the routine use of mechanical chest compressions,
      corticosteroids, thrombolytics, and adjunctive ventilation devices during arrest,
      these therapies may have an important role in select patients. Extracorporeal
      membrane oxygenation during cardiopulmonary resuscitation is a promising
      advancement and may have survival benefit in select patients. The evidence for
      standard therapies and these innovations is discussed.

PMID- 29173684
TI  - Multidisciplinary Management of the Post-Cardiac Arrest Patient.
AB  - Cardiac arrest afflicts more than 300,000 persons annually in North America
      alone. Improving outcomes after cardiac arrest requires an integrated and
      multidisciplinary approach to postresuscitation intensive care and subsequent
      recovery. This article reviews components of injury within the post-cardiac
      arrest syndrome, the salient features of brain-oriented intensive care, best
      practices in neurologic prognostication, and a rational approach to emergency
      revascularization and hemodynamic support.

PMID- 29173686
TI  - Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with
      familial Mediterranean fever.
AB  - AIM: Various mutations have been identified in the Mediterranean fever (MEFV)
      gene which is reported to be responsible from Familial Mediterranean fever (FMF).
      In our study, we aimed to determine the frequency of the MEFV mutations in our
      region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A
      (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease.
      METHODS: One hundred and sixteen patients diagnosed with FMF and 95 control
      subjects were included in this study. We used the DNA sequence analysis method to
      identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene.
      RESULTS: As a result of the MEFV mutation analysis, the most common mutation was
      the M694V mutation allele with a frequency rate of 41.8%. When the patients group
      and control group were compared in terms of frequency of both polymorphic alleles
      (G polymorphic allele, observed in G138G and the A polymorphic allele, observed
      in A165A), the variation was observed to be statistically significant (p<0.001).
      It was found that the MEFV mutation types have no relation with clinical findings
      and amyloidosis (p>0.05). CONCLUSIONS: To our knowledge, our study is the first
      study in the Southern Marmara region that reports the frequency of MEFV
      mutations. Our findings imply that the polymorphisms of G138G and A165A may have
      an impact on progress of the disease. We think that more studies, having higher
      number of cases and investigating the polymorphisms of MEFV gene, are needed.

PMID- 29173687
TI  - Development of rheumatology training in Brazil: the option for a medical
      residency program.
AB  - OBJECTIVE: To describe the characteristics and progression of the supply of new
      rheumatologists in Brazil, from 2000 to 2015. METHODS: Consultations to databases
      and official documents of institutions related to training and certification of
      rheumatologists in Brazil took place. The data were compared, summarized and
      presented descriptively. RESULTS: From 2000 to 2015, Brazil qualified 1091
      physicians as rheumatologists, of which 76.9% (n=839) completed a medical
      residency program in rheumatology (MRPR); the others (n=252) achieved this title
      without MRPR training. There was an expansion of MRPR positions. At the same
      time, there was a change in the profile of the newly qualified doctors. Early in
      the series, the fraction of new rheumatologists without MRPR, entering the market
      annually, was approaching 50%, dropping to about 15% in recent years. In 2015,
      Brazil offered 49 MRPR accredited programs, with 120 positions per year for
      access. There was an imbalance in the distribution of MRPR positions across the
      country, with a strong concentration in the southeast region, which in 2015 held
      59.2% of the positions. Public institutions accounted for 94% (n=789) of
      graduates in MRPR during the study period, while still maintaining 93.3% (n=112)
      of seats for admission in 2015. CONCLUSIONS: In the last sixteen years, in
      parallel with the expansion of places of access, MRPR has established itself as
      the preferred route for rheumatology training in Brazil, mainly supported by
      public funds. Regional inequalities in the provision of MRPR positions still
      persist, as challenges that must be faced.

PMID- 29173688
TI  - Use of pamidronate for osteoporosis treatment in public health care in Brazil.
AB  - PURPOSE: The use of bisphosphonates for osteoporosis is effective in reducing the
      risk of fractures. However, oral formulations are sometimes not well tolerated or
      are contraindicated. Due to its availability in Brazilian public health system,
      pamidronate is frequently prescribed for osteoporosis, despite the lack of
      studies demonstrating its anti-fracture efficacy and the absence of FDA or EMEA
      approval for this purpose. The aim of this study was to evaluate the bone mineral
      density (BMD) response to pamidronate in a group of women with osteoporosis in a
      tertiary care hospital. PATIENTS AND METHODS: The medical records of women with
      osteoporosis who received pamidronate for up to two years of treatment were
      reviewed. Patients were stratified at high or intermediate risk of fracture.
      RESULTS: A total of 70 women were in treatment with pamidronate. Among them, 74%
      were at high risk of fracture. A significant gain in spine BMD after 24 months of
      treatment was observed (p=0.012). There was no difference between the groups of
      high and not high risk of fracture. At the femur, no significant increase in BMD
      was present, though, a strong negative correlation with high PTH levels (r=-0.61;
      p=0.003) was seen. In the multivariate analysis BMI at 12 months had impact in
      the response to the treatment. CONCLUSION: The intravenous pamidronate in a group
      of postmenopausal women with predominant high risk of fracture promoted an
      isolated gain in the spine BMD, even though, clinical randomized trials are
      needed to confirm its anti-fracture efficacy.

PMID- 29173689
TI  - Esophageal abnormalities in juvenile localized scleroderma: is it associated with
      other extracutaneous manifestations?
AB  - OBJECTIVE: To assess esophageal involvement (EI) in juvenile localized
      scleroderma (JLS) population and the possible association between this
      gastrointestinal manifestation and demographic data, clinical features,
      laboratory exams, treatments and outcomes. METHODS: For a period of 30 years,
      5881 patients with rheumatic diseases were followed in our Pediatric Rheumatology
      Division. EI was defined by the presence of symptoms (solid/liquid dysphagia,
      heartburn, esophageal regurgitation, nausea/vomiting and epigastralgia) and
      confirmed by at least one EI exam abnormality: barium contrast radiography, upper
      gastrointestinal endoscopy and 24-hour esophageal pH-monitoring. RESULTS: JLS was
      observed in 56/5881 patients (0.9%), mainly linear morphea subtype. EI was
      observed in 23/56(41%) of JLS patients. Eight(35%) of 23 EI patients with JLS
      were symptomatic and presented heartburn(5/8), solid and liquid dysphagia(3/8),
      nausea and epigastralgia(1/8). The frequency of any cumulative extracutaneous
      manifestations (calcinosis, arthritis/arthralgia, central nervous system,
      interstitial pneumonitis, mesangial nephritis and/or arrhythmia) was
      significantly higher in JLS patients with EI compared to those without this
      complication (56% vs. 24%, p=0.024). No differences were evidenced in demographic
      data, JLS subtypes and in each extracutaneous manifestation in both groups
      (p>0.05). The frequency of methotrexate use was significantly higher in JLS
      patients with EI compared to those without (52% vs. 12%, p=0.002). Autoantibody
      profile (antinuclear antibodies, anti-SCL-70, rheumatoid factor, anticentromere,
      anti-cardiolipin, anti-Ro/SSA and anti-La/SSB) was similar in both groups
      (p>0.05). CONCLUSIONS: Our study demonstrated that EI was frequently observed in
      JLS patients, mainly in asymptomatic patients with linear subtype. EI occurred in
      JLS patients with other extracutaneous manifestations and required methotrexate
      therapy.

PMID- 29173690
TI  - Omega-3 fatty acids, inflammatory status and biochemical markers of patients with
      systemic lupus erythematosus: a pilot study.
AB  - BACKGROUND: Studies have shown that omega-3 fatty acids reduce the concentrations
      of eicosanoids, cytokines, chemokines, C-reactive protein (CRP) and other
      inflammatory mediators. OBJECTIVE: To investigate the effects of omega-3 fatty
      acids on circulating levels of inflammatory mediators and biochemical markers in
      women with systemic lupus erythematosus (SLE). METHODS: Experimental clinical
      study (clinical trial: NCT02524795); 49 women with SLE (ACR1982/1997) were
      randomized: 22 to the omega-3 group (daily intake of 1080mg EPA+200mg DHA, for 12
      weeks) and 27 to the control group. The inflammatory mediators and biochemical
      markers at T0 and T1 in omega-3 group were compared using Wilcoxon test. U-Mann
      Whitney test was used to compare variations of measured variables [DeltaV=pre
      treatment (T0)-post-treatment (T1) concentrations] between groups. p<0.05 was
      considered significant. RESULTS: The median (interquartile range - IQR) of age
      was 37 (29-48) years old, of disease duration was 7 (4-13) years, and of SLEDAI
      2K was 1 (0-2). The median (IQR) of variation in CRP levels between the two
      groups showed a decrease in omega-3 group while there was an increase in control
      group (p=0.008). The serum concentrations of IL-6 and IL-10, leptin and
      adiponectin did not change after a 12 week treatment. CONCLUSIONS:
      Supplementation with omega-3 had no impact on serum concentrations of IL-6, IL
      10, leptin and adiponectin in women with SLE and low disease activity. There was
      a significant decrease of CRP levels as well as evidence that omega-3 may impact
      total and LDL-cholesterol.

PMID- 29173691
TI  - Clinical outcomes and survival in AA amyloidosis patients.
AB  - AIM: Amyloid A amyloidosis is a rare complication of chronic inflammatory
      conditions. Most patients with amyloid A amyloidosis present with nephropathy and
      it leads to renal failure and death. We studied clinical characteristics and
      survival in patients with amyloid A amyloidosis. METHODS: A total of 81 patients
      (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were
      analyzed retrospectively. The patients were divided into good and poor outcomes
      groups according to survival results. RESULTS: Most of the patients (55.6%) had
      nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were
      familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good
      outcome group and malignancy (20%) in the poor outcome group. Only diastolic
      blood pressure in the good outcome group and phosphorus level in the poor outcome
      group was higher. Serum creatinine levels increased after treatment in both
      groups, while proteinuria in the good outcome group decreased. Increase in serum
      creatinine and decrease in estimated glomerular filtration rate of the poor
      outcome group were more significant in the good outcome group. At the time of
      diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease
      (stage 4 and 5, respectively). Median duration of renal survival was 65+/-3.54
      months. Among all patients, 27.1% were started dialysis treatment during the
      follow-up period and 7.4% of all patients underwent kidney transplantation.
      Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence
      interval: 1-1.06, p=0.036], serum creatinine (hazard ratios 1.25, 95% confidence
      interval: 1.07-1.46, p=0.006) and urinary protein excretion (hazard ratios 1.08,
      95% confidence interval: 1.01-1.16, p=0.027) were predictors of end-stage renal
      disease. Median survival of patients with organ involvement was 50.3+/-16 months.
      CONCLUSION: Our study indicated that familial Mediterranean fever constituted a
      large proportion of cases and increased number of patients with idiopathic
      amyloid A amyloidosis. Additionally, it was observed that patient survival was
      not affected by different etiological causes in amyloid A amyloidosis.

PMID- 29173692
TI  - Socioeconomic and therapy factor influence on self-reported fatigue, anxiety and
      depression in rheumatoid arthritis patients.
AB  - INTRODUCTION: Fatigue, anxiety and depression are very frequent symptoms in
      patients with rheumatoid arthritis (RA). GOALS: In this study we evaluated the
      influence of socioeconomic characteristics, therapy and comorbidities on the self
      reported high fatigue, anxiety and depression in patients with RA. METHOD:
      Multicenter cross-sectional study was performed in 22 health institutions in
      Serbia during the period from April-August 2014 in population of older RA
      patients. Self-reported patients health status was measured by: Fatigue
      Assessment Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder
      7. Treatment modalities were defined as: (1) non-steroidal anti-inflammatory
      drugs (NSAIDs) and/or analgesics and/or corticosteroids; (2) synthetic disease
      modifying antirheumatic drugs (DMARDs) alone or in combination with
      corticosteroids and/or NSAIDs and (3) any RA treatment which includes biologic
      DMARDs. RESULTS: There were significant predictors of high depression: synthetic
      DMARDs therapy in combination with corticosteroids and/or NSAIDs, physiotherapist
      self-payment, frequent taxi use, alternative treatment and employment status. The
      need for another person's assistance, supplemental calcium therapy and
      professional qualifications were the predictors of a high fatigue, whereas the
      age above 65 years had the protective effect on it. Anxiety was an independent
      high fatigue predictor. The predictors of a high anxiety were: gastroprotection
      with proton-pump inhibitors and patient occupation. CONCLUSION: Socioeconomic
      predictors of self-reported high depression, anxiety or fatigue are different for
      each of the mentioned outcomes, while accompanied with the basic RA treatment
      they exclusively explain a high depression. The anxiety, jointed with the
      socioeconomic variables and supplemental therapy, is a significant fatigue
      predictor in RA patients.

PMID- 29173693
TI  - Three cases of anti-TNF induced myositis and literature review.
AB  - Anti-tumor necrosis factor drugs are frequently preferred in the treatment of
      rheumatologic diseases and other inflammatory diseases. The development of
      myositis after using anti-tumor necrosis factor drugs is a rare clinical
      condition. Here we aimed to report cases who developed myositis after using anti
      tumor necrosis factor drugs and review the current literature. We report two
      cases of rheumatoid arthritis and a case of ankylosing spondylitis developed
      idiopathic inflammatory myopathy following anti-tumor necrosis factor therapy. In
      conclusion, myositis could develop during anti-tumor necrosis factor therapy, so
      these patients should be evaluated carefully initially for myositis and should be
      closely monitored due to the potential for developing myositis in treatment
      process.

PMID- 29173694
TI  - Cyclophosphamide administration routine in autoimmune rheumatic diseases: a
      review.
AB  - Cyclophosphamide is an alkylating agent widely used for the treatment of
      malignant neoplasia and which can be used in the treatment of multiple rheumatic
      diseases. Medication administration errors may lead to its reduced efficacy or
      increased drug toxicity. Many errors occur in the administration of injectable
      drugs. The present study aimed at structuring a routine for cyclophosphamide use,
      as well as creating a document with pharmacotherapeutic guidelines for the
      patient. The routine is schematized in three phases: pre-chemotherapy,
      administration of cyclophosphamide, and post-chemotherapy, taking into account
      the drugs to be administered before and after cyclophosphamide in order to
      prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse
      reactions can alter laboratory tests; thus, this routine included clinical
      management for changes in white blood cells, platelets, neutrophils, and sodium,
      including cyclophosphamide dose adjustment in the case of kidney disease.
      Cyclophosphamide is responsible for other rare - but serious - side effects, for
      instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse
      reactions include hair loss, amenorrhea and menopause. In this routine, we also
      entered guidelines to post-chemotherapy patients. The compatibility of injectable
      drugs with the vehicle used has been described, as well as stability and infusion
      times. The routine aimed at the rational use of cyclophosphamide, with prevention
      of adverse events and relapse episodes, factors that may burden the health care
      system.

PMID- 29173695
TI  - Scientific people named in the classification of vasculitis.
AB  - The first International Chapel Hill Consensus Conference was held in 1994. There
      have been suggestions about the nomenclature of systemic vasculitis. Important
      categories were added to the classification of vasculitis, and many changes were
      made for disease names in the second Chapel Hill Consensus Conference 2012, which
      were not included in the Chapel Hill Consensus Conference 1994. The new
      nomenclature was introduced instead of being referred to by many names such as
      Churg-Strauss and Wegener"s. New categories such as Behcet"s and Cogan etc. were
      also added. These people are honored by the classification. They contribute to
      science through their case studies, scientific articles, and observations. This
      article reviews only eponyms present in the current classification of vasculitis.
      The aim of this paper is to give information about scientists mentioned in the
      classification of vasculitis.

PMID- 29173696
TI  - Presence of riziform bodies in a patient with juvenile idiopathic arthritis: case
      report and literature review.

PMID- 29173697
TI  - Nephrotic syndrome as the first manifestation of juvenile systemic scleroderma.

PMID- 29173698
TI  - Reduced activation and CD3 lymphocyte recruitment after TNF-inhibitor use:
      evaluation of clinical and 99mTc-OKT3 scintigraphic response in a patient with
      juvenile idiopathic arthritis.

PMID- 29173699
TI  - Lyme disease and juvenile idiopathic arthritis - A pediatric case report.

PMID- 29173700
TI  - Relapsing polychondritis and lymphocytic meningitis with varied neurological
      symptoms.

PMID- 29173701
TI  - Initial isolated Takayasu's arteritis of bilateral pulmonary artery branches.

PMID- 29173702
TI  - Leprosy simulating systemic sclerosis: a case report.

PMID- 29173703
TI  - Case-control study of vitamin D receptor gene polymorphism in Pakistani
      rheumatoid arthritis patients.

PMID- 29173704
TI  - Hepcidin-25 gives an indication of the therapeutic effectiveness of tocilizumab
      in rheumatoid arthritis - Relationship between disease activity of rheumatoid
      arthritis and anemia.

PMID- 29173705
TI  - Intracellular Signaling Pathways Involved in (S)- and (R)-Ketamine Antidepressant
      Actions.

PMID- 29173706
TI  - Stress, Depression, and Inflammation: Molecular and Microglial Mechanisms.

PMID- 29173707
TI  - Risks for Major Depression: Searching for Stable Traits.

PMID- 29173708
TI  - Small RNAs May Answer Big Questions in Mental Illness.

PMID- 29173709
TI  - New Insight Into the Mechanisms of Fast-Acting Antidepressants: What We Learn
      From Scopolamine.

PMID- 29173710
TI  - The Journey to Interprofessional Collaborative Practice: Are We There Yet?
AB  - Interprofessional collaborative practice (IPCP) is a service delivery approach
      that seeks to improve health care outcomes and the patient experience while
      simultaneously decreasing health care costs. The current article reviews the core
      competencies and current trends associated with IPCP, including challenges faced
      by health care practitioners when working on interprofessional teams. Several
      conceptual frameworks and empirically supported interventions from the fields of
      organizational psychology and organization development are presented to assist
      health care professionals in transitioning their teams to a more
      interprofessionally collaborative, team-based model of practice.

PMID- 29173711
TI  - Otitis Media: Beyond the Examining Room.
AB  - The management of hearing loss associated with otitis media is multifaceted.
      Clinical practice guidelines set the collaborative prescriptive standards for the
      medical management of otitis media in children. Treatment of this condition does
      not end with the medical practitioner. There are far-reaching effects of otitis
      media and its sequelae that permeate every aspect of patients' lives including
      physiological, educational, and psychosocial. Therefore, a comprehensive
      interprofessional treatment plan must be designed taking into consideration best
      practices from a range of professions to maximize clinical outcomes, including
      the treating physician, speech-language pathologist, clinical audiologist,
      educational audiologist, and professionals in the educational setting.

PMID- 29173712
TI  - Using the International Classification of Functioning, Disability and Health
      Framework to Achieve Interprofessional Functional Outcomes for Young Children: A
      Speech-Language Pathology Perspective.
AB  - The International Classification of Functioning, Disability and Health (ICF)
      framework is an excellent tool to facilitate the writing of functional goals for
      children who exhibit communication disorders and other developmental problems
      that require services from professionals in multiple therapeutic areas. The
      holistic view of children provides each professional with an approach that
      integrates how one's specific health conditions and contextual factors influence
      a child's functioning and participation in daily activities. This allows the
      interprofessional team to view the child as a person, recognizing how one need
      influences another within his or her environment.

PMID- 29173713
TI  - Late Talkers: Why the Wait-and-See Approach Is Outdated.
AB  - From a speech-language pathology perspective, there is a gap in interprofessional
      education/practice (IPE/IPP) that leads to a wait-and-see approach with late
      talkers (LT). In line with the American Speech-Language-Hearing Association's
      Strategic Pathway to Excellence, this article attempts to bridge the gap,
      reexamining the panoptic view that most LT "catch up" to their peers. The LT who
      persist with language disorder should not be overlooked. Late talking can impact
      socialization and school readiness, and can place some toddlers at risk for life
      long disability. Each state's early intervention program has an established IPP
      infrastructure. Parent-implemented intervention addresses risks and maximizes
      protective factors.

PMID- 29173714
TI  - Developmental and Interprofessional Care of the Preterm Infant: Neonatal
      Intensive Care Unit Through High-Risk Infant Follow-up.
AB  - Practices in the neonatal intensive care unit (NICU) that reduce infant stress
      and respond to behavioral cues positively influence developmental outcomes.
      Proactive developmental surveillance and timely introduction of early
      intervention services improve outcomes for premature infants. A model that
      emphasizes infant development and a continuum of care beginning in the NICU with
      transition to outpatient monitoring and provision of early intervention services
      is hypothesized to support the most optimal outcomes for premature infants.

PMID- 29173715
TI  - Interprofessional Collaborative Practice in Early Intervention.
AB  - Professionals in pediatric practice encounter infants and toddlers with
      developmental delays, disabilities, or complex chronic health conditions eligible
      for Part C early intervention (EI) services. The most frequently identified
      concern by families is communication emphasizing the importance of the role of
      the speech language pathologist (SLP). This article provides a conceptual
      framework for SLP services in early intervention, based on the principles of
      interprofessional collaboration. The history of collaboration, EI, and the role
      of SLPs as members of the EI team are summarized. The competencies mandated for
      interprofessional education and practice are juxtaposed with the principles of EI
      and guidelines for SLPs.

PMID- 29173716
TI  - The Role of the Speech-Language Pathologist in Creating a Model for
      Interprofessional Practice in an Ambulatory Care Clinic.
AB  - There is a need to better coordinate services for children in urban settings who
      are at risk for communication disorders. This article addresses the barriers to
      obtaining services and discusses the process for creating a model for
      interprofessional practice to better serve patients from lower socioeconomic
      backgrounds.

PMID- 29173717
TI  - The Future of Pediatric Speech-Language Pathology in a More Collaborative World.
AB  - Examining interprofessional practice through the lens of speech-language
      pathology identifies a number of challenges to and opportunities for
      interprofessional practice. While practitioners believe they practice
      interprofessionally, health services are often distributed across a network
      within which collaboration can falter. Certain professions, like speech-language
      pathology, are well-positioned to work across this network and improve care.
      Barriers to collaboration are interpersonal, structural, regulatory, and
      governmental. To enhance interprofessional practice, students should receive
      interprofessional education; practitioners should engage in interprofessional
      continuing education based on their practice environment; and leaders and
      researchers should identify frameworks to support better interprofessional
      practice.

PMID- 29173718
TI  - A Pediatrician's Guide to Communication Disorders Secondary to Cleft Lip/Palate.
AB  - This article describes how different types of clefts affect the child's function
      and, in particular, the child's communication abilities. This article also
      describes the evaluation process and various options for the treatment of
      affected speech. Because these children have many complicated needs over their
      entire growth period, it is important that they are referred by the pediatrician
      to a cleft palate/craniofacial team for the best care and best ultimate outcomes.

PMID- 29173719
TI  - Supporting Children with Autism and Their Families: A Culturally Responsive
      Family-Driven Interprofessional Process.
AB  - This article describes the Coaching in Context (CinC) process, a family-driven,
      culturally responsive structure that facilitates family identification and
      achievement of goals. CinC focuses on modification of the demands of an activity
      with guidance from a health care professional who coaches the family to increase
      their participation in everyday activities. An interprofessional team is key in
      this process. Working as a team and communicating effectively across professions
      supports the health professional who serves as the coach. Effective
      interprofessional team collaboration is possible; health professions share values
      for the delivery of the highest quality of care.

PMID- 29173720
TI  - Feeding Problems in Infants and Children: Assessment and Etiology.
AB  - Feeding problems in infants and young children are common. In healthy children
      who are developing and growing normally, feeding problems are usually not serious
      and can be managed conservatively by reassuring the family and providing them
      with anticipatory guidance and follow-up. A majority of serious childhood feeding
      problems occur in children who have other medical, developmental, or behavioral
      problems. These are best evaluated and treated by an interprofessional team who
      can identify and address issues in the medical and/or developmental history,
      problems with oral motor control and function, problems with swallowing, and
      behavioral and/or sensory issues that may interfere with normal feeding.

PMID- 29173721
TI  - An Interprofessional Team Approach to the Differential Diagnosis of Children with
      Language Disorders.
AB  - The ability to communicate effectively with others is central to children's
      development. Delays or disruptions due to isolated expressive language delay,
      articulation errors, multiple sound production errors with motor planning
      deficits, or mixed expressive and receptive language delay, often bring
      widespread consequences. Physical anomalies, neurologic and genetic disorder,
      cognitive and intellectual disabilities, and emotional disturbances may affect
      speech and language development. Communication disorders may be misdiagnosed as
      intellectual impairment or autism. Interdisciplinary evaluation should include
      speech and language assessment, physical and neurologic status, cognitive and
      emotional profile, and family and social history. This article describes
      assessment and reviews common pediatric communication disorders.

PMID- 29173722
TI  - Open Up and Let Us In: An Interprofessional Approach to Oral Health.
AB  - Dental caries is the single most common chronic disease of childhood in the
      United States. Access to dental care is one of the barriers to improved oral
      health for children. Primary care providers who routinely treat children have an
      established role in prevention and early identification of health problems; thus,
      they are ideal front-line providers who can detect oral health discrepancies and
      begin the process of care and prevention.

PMID- 29173723
TI  - Pediatric Speech and Language: Perspectives on Interprofessional Practice.

PMID- 29173724
TI  - Pediatric Speech and Language Perspectives on Interprofessional Practice.

PMID- 29173725
TI  - Hyaluronan and Hyaluronan Fragments.
AB  - The glycosaminoglycan hyaluronan (HA) is a key component of the microenvironment
      surrounding cells. In healthy tissues, HA molecules have extremely high molecular
      mass and consequently large hydrodynamic volumes. Tethered to the cell surface by
      clustered receptor proteins, HA molecules crowd each other, as well as other
      macromolecular species. This leads to severe nonideality in physical properties
      of the biomatrix, because steric exclusion leads to an increase in effective
      concentration of the macromolecules. The excluded volume depends on both polymer
      concentration and hydrodynamic volume/molecular mass. The biomechanical
      properties of the extracellular matrix, tissue hydration, receptor clustering,
      and receptor-ligand interactions are strongly affected by the presence of HA and
      by its molecular mass. In inflammation, reactive oxygen and nitrogen species
      fragment the HA chains. Depending on the rate of chain degradation relative to
      the rates of new synthesis and removal of damaged chains, short fragments of the
      HA molecules can be present at significant levels. Not only are the physical
      properties of the extracellular matrix affected, but the HA fragments decluster
      their primary receptors and act as endogenous danger signals. Bioanalytical
      methods to isolate and quantify HA fragments have been developed to determine
      profiles of HA content and size in healthy and diseased biological fluids and
      tissues. These methods have potential use in medical diagnostic tests.
      Therapeutic agents that modulate signaling by HA fragments show promise in wound
      healing and tissue repair without fibrosis.

PMID- 29173726
TI  - The Synthesis and Biological Characterization of Acetal-Free Mimics of the Tumor
      Associated Carbohydrate Antigens.
AB  - Carcinomas express unique carbohydrates, known as tumor-associated carbohydrate
      antigens (TACAs), on their surface. These are potential targets for anticancer
      vaccines; however, to date, no such vaccine has reached the clinic. One factor
      that may complicate the success of this effort is the lability of the glycosidic
      bond. Acetal-free carbohydrates are analogues that lack the glycosidic linkage by
      replacing either the endo or exo oxygen with a methylene. This chapter summarizes
      the seminal syntheses of the mucin TACAs, provides an overview of common
      techniques for the synthesis of carbasugars and C-glycosides, reviews the
      syntheses published to date of acetal-free TACA analogues, and provides an
      overview of their observed biological activity. We conclude by offering a
      summation of the challenges remaining to the field biologically and the potential
      that acetal-free TACAs have of answering several basic questions in carbohydrate
      immunology.

PMID- 29173727
TI  - Application of Porous Materials to Carbohydrate Chemistry and Glycoscience.
AB  - There is a growing interest in using a range of porous materials to meet research
      needs in carbohydrate chemistry and glycoscience in general. Among the
      applications of porous materials reviewed in this chapter, enrichment of glycans
      from biological samples prior to separation and analysis by mass spectrometry is
      a major emphasis. Porous materials offer high surface area, adjustable pore
      sizes, and tunable surface chemistry for interacting with glycans, by boronate
      affinity, hydrophilic interactions, molecular imprinting, and polar interactions.
      Among the materials covered in this review are mesoporous silica and related
      materials, porous graphitic carbon, mesoporous carbon, porous polymers, and
      nanoporous gold. In some applications, glycans are enzymatically or chemically
      released from glycoproteins or glycopeptides, and the porous materials have the
      advantage of size selectivity admitting only the glycans into the pores and
      excluding proteins. Immobilization of lectins onto porous materials of suitable
      pore size allows for the use of lectin-carbohydrate interactions in capture or
      separation of glycoproteins. Porous material surfaces modified with carbohydrates
      can be used for the selective capture of lectins. Controlled release of
      therapeutics from porous materials mediated by glycans has been reported, and so
      has therapeutic targeting using carbohydrate-modified porous particles.
      Additional applications of porous materials in glycoscience include their use in
      the supported synthesis of oligosaccharides and in the development of biosensors
      for glycans.

PMID- 29173728
TI  - Preface.

PMID- 29173729
TI  - Andres Martin, MD, MPH, JAACAP Editor-in-Chief, 2008-2017.

PMID- 29173730
TI  - From Here to There: The Journal's Other Pipeline.

PMID- 29173731
TI  - Gene Genie of Bipolar Disorder, We Have a Few More Wishes.

PMID- 29173732
TI  - Clinical Relevance Versus Statistical Significance.

PMID- 29173733
TI  - Exposure Tasks in Anxiety Treatment: A Black Box That Still Needs Unpacking.

PMID- 29173734
TI  - Partnering With Child-Serving Professional Organizations: The Example of Early
      Childhood Mental Health Policy.

PMID- 29173735
TI  - Efficacy and Safety of Lurasidone in Children and Adolescents With Bipolar I
      Depression: A Double-Blind, Placebo-Controlled Study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of lurasidone in children and
      adolescents with bipolar depression. METHOD: Patients 10 to 17 years old with a
      DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double
      blind treatment with flexible doses of lurasidone 20 to 80 mg/day. The primary
      endpoint was change from baseline to week 6 in the Children's Depression Rating
      Scale-Revised (CDRS-R) total score, evaluated by a mixed-model repeated-measures
      analysis. RESULTS: A total of 347 patients were randomized and received at least
      1 dose of lurasidone (n = 175; mean age 14.2 years; mean dose 33.6 mg/day) or
      placebo (n = 172; mean age 14.3 years). At week 6, treatment with lurasidone was
      associated with statistically significant improvement compared with placebo in
      CDRS-R total score (-21.0 versus -15.3; p < .0001; effect size 0.45). Lurasidone
      also was associated with statistically significant improvement in the Clinical
      Global Impression-Bipolar Severity depression score (key secondary measure) and
      in measures of anxiety, quality of life, and global functioning. Study completion
      rates were 92.0% in the lurasidone group and 89.7% in the placebo group;
      discontinuation rates due to adverse events were the same for the 2 groups
      (1.7%). The 2 most common adverse events on lurasidone were nausea and
      somnolence. Treatment with lurasidone was associated with few effects on weight
      and metabolic parameters. CONCLUSION: In this placebo-controlled study,
      monotherapy with lurasidone, in the dose range of 20 to 80 mg/day, significantly
      decreased depressive symptoms in children and adolescents with bipolar
      depression. Lurasidone was well tolerated, with minimal effects on weight and
      metabolic parameters. Clinical trial registration information-Lurasidone
      Pediatric Bipolar Study; http://Clinicaltrials.gov; NCT02046369.

PMID- 29173736
TI  - Clinical Implications From the Treatment of Severe Childhood Aggression (TOSCA)
      Study: A Re-Analysis and Integration of Findings.
AB  - OBJECTIVE: The Treatment of Severe Childhood Aggression (TOSCA) project examined
      augmentation of stimulant treatment and parent training (PT) with risperidone for
      severe physical aggression. This article summarizes the clinical implications;
      reanalyzes the data to examine the utility of 4 criteria for deciding to augment;
      and presents a treatment algorithm. METHOD: The newly analyzed 4 criteria for
      augmenting after 3 weeks of stimulant and PT treatment consisted of not meeting a
      Clinical Global Impressions-Improvement (CGI-I) score of 1 and a normal score
      (<=15) on the Nisonger Child Behavior Rating Form Disruptive-Total (D-Total); a
      CGI-I score of 1 or 2 plus 25% improvement in D-Total score; a D-Total score no
      higher than 15; and a CGI-Severity score of 3 (mild) or better. Effect sizes were
      calculated. Prior TOSCA publications were reviewed for clinically relevant
      findings. RESULTS: All 4 criteria resulted in medium or better effect sizes (d =
      0.59-0.72) when comparing risperidone with placebo. Providing risperidone to
      children who did not reach a CGI-I score of 1 plus a D-Total score no higher than
      15 resulted in the greatest benefit. In addition, a review of clinically relevant
      data suggests that stimulant plus PT shows further improvement after 3 weeks even
      without augmentation. CONCLUSION: For those children who did not attain a CGI-I
      score of 1 and a D-total score no higher than 15, adding risperidone maximized
      the number of children benefitting from treatment and the average amount of
      benefit. Unless clinical circumstances dictate otherwise, practitioners should
      delay an antipsychotic drug for at least 1 month after the optimal stimulant dose
      is achieved and PT has commenced. Clinical trial registration information
      Treatment of Severe Childhood Aggression (The TOSCA Study);
      http://clinicaltrials.gov; NCT00796302.

PMID- 29173737
TI  - Targeted Family Intervention for Complex Cases of Pediatric Obsessive-Compulsive
      Disorder: A Randomized Controlled Trial.
AB  - OBJECTIVE: Although evidence-based treatments for pediatric obsessive-compulsive
      disorder (OCD) exist, many youth fail to respond, and interventions tailored to
      the needs of specific subsets of patients are lacking. This study examines the
      efficacy of a family intervention module designed for cases of OCD complicated by
      poor family functioning. METHOD: Participants were 62 youngsters aged 8 to 17
      years (mean age = 12.71 years; 57% male; 65% white) with a primary diagnosis of
      OCD and at least 2 indicators of poor family functioning. They were randomized to
      receive 12 sessions of individual child cognitive-behavioral therapy (CBT) plus
      weekly parent psychoeducation and session review (standard treatment [ST]) or the
      same 12 child sessions plus 6 sessions of family therapy aimed at improving OCD
      related emotion regulation and problem solving (positive family interaction
      therapy [PFIT]). Blinded raters evaluated outcomes and tracked responders to 3
      month follow-up. RESULTS: Compared to ST, PFIT demonstrated better overall
      response rates on the Clinician Global Impression-Improvement scale (CGI-I; 68%
      versus 40%, p = .03, phi = 0.28) and rates of remission (58% PFIT versus 27% ST,
      p = .01, phi = 0.32). PFIT also produced significantly greater reductions in
      functional impairment, symptom accommodation, and family conflict, and
      improvements in family cohesion. As expected, these shifts in family functioning
      constitute an important treatment mechanism, with changes in accommodation
      mediating treatment response. CONCLUSION: PFIT is efficacious for reducing OCD
      symptom severity and impairment and for improving family functioning. Findings
      are discussed in terms of personalized medicine and mechanisms of change in
      pediatric OCD treatment. Clinical trial registration information-Family Focused
      Treatment of Pediatric Obsessive Compulsive Disorder; http://clinicaltrials.gov/;
      NCT01409642.

PMID- 29173738
TI  - Therapist-Reported Features of Exposure Tasks That Predict Differential Treatment
      Outcomes for Youth With Anxiety.
AB  - OBJECTIVE: Exposure tasks are recognized widely as a key component of cognitive
      behavioral therapy (CBT) for child and adolescent anxiety. However, little
      research has examined specific exposure characteristics that predict outcomes for
      youth with anxiety and that may guide its application in therapy. METHOD: This
      study draws on a sample of 279 children and adolescents (48.4% male; 79.6% white)
      with a principal anxiety disorder who received 14 sessions of CBT, either alone
      or in combination with medication, through the Child/adolescent Anxiety
      Multimodal treatment Study (CAMS). The present study examines therapist-reported
      quantity, difficulty level, compliance, and mastery of exposure tasks as they
      related to CBT response (i.e., Clinical Global Impressions-Improvement ratings).
      Secondary treatment outcomes included reduction in anxiety symptom severity on
      the Pediatric Anxiety Rating Scale, global impairment measured via the Children's
      Global Assessment Scale, and parent-report of anxiety-specific functional
      impairment on the Child Anxiety Impairment Scale. RESULTS: Regression analyses
      indicated a dose-response relationship between therapist-reported quantity of
      exposure and independent evaluations of treatment outcome, with more time devoted
      to exposure linked to better outcomes. Similarly, greater time spent on more
      difficult (rather than mild or moderate) exposure tasks predicted better
      outcomes, as did therapist ratings of child compliance and mastery. CONCLUSION:
      The present findings highlight the importance of challenging children and
      adolescents with difficult exposure tasks and of collaborating to ensure
      compliance and mastery.

PMID- 29173739
TI  - A Two-Week Psychosocial Intervention Reduces Future Aggression and Incarceration
      in Clinically Aggressive Juvenile Offenders.
AB  - OBJECTIVE: There is a largely unmet need for evidence-based interventions that
      reduce future aggression and incarceration in clinically aggressive juvenile
      offenders serving probation. We addressed this gap using a group randomized
      controlled trial. Offenders both with and without clinical aggression were
      included, enabling comparison of intervention effects. METHOD: Juveniles 13 to 17
      years old (N = 310, mean = 16 years, 90% African-American, 66% male) on probation
      were assigned to a 2-week intervention targeting psychosocial factors implicated
      in risky behavior (e.g., learning strategies to manage "hot" emotions that prompt
      risk taking) or to an equally intensive health promotion control. Participants
      completed aggression measures at baseline, 6-, and 12-month follow-up and
      reported on incarceration at 12 months. Spline regression tested symptom change.
      RESULTS: Among clinically aggressive offenders (n = 71), the intervention arm
      showed significantly greater reductions in aggression over the first 6 months
      compared with controls. Juveniles from the intervention no longer met clinical
      criteria, on average, but clinically significant symptoms persisted in the
      control group. By 12 months, participants from the intervention appeared to
      maintain treatment gains, but their symptom levels no longer differed
      significantly from those in the control. However, the intervention group was
      nearly 4 times less likely than controls to report incarceration. Intervention
      effects were significantly stronger for offenders with clinical than with
      nonclinical (n = 239) baseline aggression. CONCLUSION: A 2-week intervention
      expedited improvements in aggression and reduced incarceration in clinically
      aggressive juvenile offenders. The findings underscore the importance of
      directing intervention resources to the most aggressive youth. Clinical trial
      registration information-PHAT Life: Preventing HIV/AIDS Among Teens in Juvenile
      Justice (PHAT Life); http://clinicaltrials.gov/; NCT02647710.

PMID- 29173740
TI  - The Dissociative Subtype of Posttraumatic Stress Disorder (PTSD) Among
      Adolescents: Co-Occurring PTSD, Depersonalization/Derealization, and Other
      Dissociation Symptoms.
AB  - OBJECTIVE: The purpose of this study was to examine the co-occurrence of
      posttraumatic stress disorder (PTSD) and dissociation in a clinical sample of
      trauma-exposed adolescents by evaluating evidence for the
      depersonalization/derealization dissociative subtype of PTSD as defined by the
      DSM-5 and then examining a broader set of dissociation symptoms. METHOD: A sample
      of treatment-seeking, trauma-exposed adolescents 12 to 16 years old (N = 3,081)
      from the National Child Traumatic Stress Network Core Data Set was used to meet
      the study objectives. Two models of PTSD/dissociation co-occurrence were
      estimated using latent class analysis, one with 2 dissociation symptoms and the
      other with 10 dissociation symptoms. After model selection, groups within each
      model were compared on demographics, trauma characteristics, and psychopathology.
      RESULTS: Model A, the depersonalization/derealization model, had 5 classes:
      dissociative subtype/high PTSD; high PTSD; anxious arousal; dysphoric arousal;
      and a low symptom/reference class. Model B, the expanded dissociation model,
      identified an additional class characterized by dissociative amnesia and detached
      arousal. CONCLUSION: These 2 models provide new information about the specific
      ways PTSD and dissociation co-occur and illuminate some differences between adult
      and adolescent trauma symptom expression. A dissociative subtype of PTSD can be
      distinguished from PTSD alone in adolescents, but assessing a wider range of
      dissociative symptoms is needed to fully characterize adolescent traumatic stress
      responses.

PMID- 29173741
TI  - Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk
      for Suicide Attempts.
AB  - OBJECTIVE: Bipolar disorder (BD) is one of the most heritable psychiatric
      conditions and is associated with high suicide risk. To explore the reasons for
      this link, this study examined the interaction between traumatic stress and BD
      polygenic risk score in relation to suicidal ideation, suicide attempt, and
      nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and
      relatives of persons with BD (BD-relatives) compared with adolescent and young
      adult offspring of individuals without psychiatric disorders (controls). METHOD:
      Data were collected from 4 sites in the United States and 1 site in Australia
      from 2006 through 2012. Generalized estimating equation models were used to
      compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and
      controls (n = 166) and to determine the contribution of demographic factors,
      traumatic stress exposure, lifetime mood or substance (alcohol/drug) use
      disorders, and BD polygenic risk score. RESULTS: After adjusting for demographic
      characteristics and mood and substance use disorders, BD-relatives were at
      increased risk for suicidal ideation and attempts but not for NSSI. Independent
      of BD-relative versus control status, demographic factors, or mood and substance
      use disorders, exposure to trauma within the past year (including bullying,
      sexual abuse, and domestic violence) was associated with suicide attempts (p =
      .014), and BD polygenic risk score was marginally associated with attempts (p =
      .061). Importantly, the interaction between BD polygenic risk score and traumatic
      event exposures was significantly associated with attempts, independent of
      demographics, relative versus control status, and mood and substance use
      disorders (p = .041). CONCLUSION: BD-relatives are at increased risk for suicide
      attempts and ideation, especially if they are exposed to trauma and have evidence
      of increased genetic vulnerability.

PMID- 29173742
TI  - Developmental Psychopathology in a Racial/Ethnic Minority Group: Are Cultural
      Risks Relevant?
AB  - OBJECTIVE: The current study examined (a) the mediating role of parenting
      behaviors in the relationship between parental risks and youth antisocial
      behaviors (YASB), and (b) the role of youth cultural stress in a racial/ethnic
      minority group (i.e., Puerto Rican [PR] youth). METHOD: This longitudinal study
      consisted of 3 annual interviews of PR youth (N = 1,150; aged 10-14 years at wave
      1) and their caretakers from the South Bronx (SB) in New York City and from San
      Juan, Puerto Rico. Parents reported on parental risks, parenting behaviors, and
      YASB. Youth also self-reported on YASB and youth cultural stress. A lagged
      structural equation model examined the relationship between these variables
      across 3 yearly waves, with youth cultural stress as a moderator of the
      association between effective parenting behaviors and YASB. RESULTS: Findings
      supported the positive influence of effective parenting on YASB, independently of
      past parental risks and past YASB: higher effective parenting significantly
      predicted lower YASB at the following wave. Parenting also accounted for
      (mediated) the association between the composite of parental risks and YASB.
      Youth cultural stress at wave 1 was cross-sectionally associated with higher YASB
      and moderated the prospective associations between effective parenting and YASB,
      such that for youth who perceived higher cultural stress, the positive effect of
      effective parenting on YASB was weakened compared to those with lower/average
      cultural stress. CONCLUSION: Among PR families, both parental and cultural risk
      factors influence YASB. Such findings should be considered when treating
      racial/ethnic minority youth for whom cultural factors may be a relevant
      influence on determining behaviors.

PMID- 29173743
TI  - Clinical Correlates of Carbon Dioxide Hypersensitivity in Children.
AB  - OBJECTIVE: Hypersensitivity to carbon dioxide (CO2)-enriched air may be a
      promising risk marker for anxiety disorders. Among adult and adolescent samples,
      heterogeneity in distress response to the CO2 challenge task indexes 3 underlying
      classes of individuals, which distinguish between sustained and acute threat
      response as markers for internalizing disorders, broadly, and anxiety disorders,
      specifically. The present study examines latent classes in children's response to
      the CO2 challenge task to clarify the association of CO2 hypersensitivity with
      anxiety and internalizing symptomatology in childhood. METHOD: Healthy children
      from a community twin sample (N = 538; age 9-13 years) rated anxious distress
      every 2 minutes while breathing air enriched to 7.5% CO2 for 8 minutes. Latent
      growth mixture modeling evaluated potential classes of individuals with
      characteristic trajectories of distress during the task to clarify the
      association with internalizing disorder symptoms and related traits (e.g.,
      anxiety sensitivity, irritability). RESULTS: Although all participants reported
      increased distress during the task, interindividual heterogeneity in distress
      indexed 3 underlying classes: a consistently low class ("low"), a consistently
      high class ("high"), and participants who demonstrated markedly increased acute
      distress ("acute"). Compared to the low class, the high class reported greater
      internalizing psychopathology, whereas membership in the acute class was
      associated with experiencing a panic-like event during the task. CONCLUSION: As
      in older individuals, 3 distinct trajectories emerged to capture interindividual
      heterogeneity in children's distress during the CO2 challenge task. These classes
      were distinguished by clinical validators that reinforce the association of CO2
      hypersensitivity and internalizing disorder phenotypes in children.

PMID- 29173744
TI  - A Neurobehavioral Mechanism Linking Behaviorally Inhibited Temperament and Later
      Adolescent Social Anxiety.
AB  - OBJECTIVE: Behavioral inhibition (BI) is a temperament identified in early
      childhood that is a risk factor for later social anxiety. However, mechanisms
      underlying the development of social anxiety remain unclear. To better understand
      the emergence of social anxiety, longitudinal studies investigating changes at
      behavioral neural levels are needed. METHOD: BI was assessed in the laboratory at
      2 and 3 years of age (N = 268). Children returned at 12 years, and an
      electroencephalogram was recorded while children performed a flanker task under 2
      conditions: once while believing they were being observed by peers and once while
      not being observed. This methodology isolated changes in error monitoring (error
      related negativity) and behavior (post-error reaction time slowing) as a function
      of social context. At 12 years, current social anxiety symptoms and lifetime
      diagnoses of social anxiety were obtained. RESULTS: Childhood BI prospectively
      predicted social-specific error-related negativity increases and social anxiety
      symptoms in adolescence; these symptoms directly related to clinical diagnoses.
      Serial mediation analysis showed that social error-related negativity changes
      explained relations between BI and social anxiety symptoms (n = 107) and
      diagnosis (n = 92), but only insofar as social context also led to increased post
      error reaction time slowing (a measure of error preoccupation); this model was
      not significantly related to generalized anxiety. CONCLUSION: Results extend
      prior work on socially induced changes in error monitoring and error
      preoccupation. These measures could index a neurobehavioral mechanism linking BI
      to adolescent social anxiety symptoms and diagnosis. This mechanism could relate
      more strongly to social than to generalized anxiety in the peri-adolescent
      period.

PMID- 29173745
TI  - Adieuvalence.

PMID- 29173746
TI  - Handoff: Editor's Annual Report-Volume 56, 2017.

PMID- 29173747
TI  - Invisible Allies: Thanking Our Reviewers.

PMID- 29173748
TI  - Transparency: Disclosure of Financial Interests.

PMID- 29173749
TI  - Introduction.

PMID- 29173750
TI  - Role of Immunotherapy in Head and Neck Cancer.
AB  - Immune system dysfunction plays a role in both the development and progression of
      head and neck squamous cell carcinoma (HNSCC), highlighting the potential role
      for immunotherapy to improve outcomes in this disease. The application of anti-PD
      1 therapies for recurrent or metastatic HNSCC has found promising results. This
      has led to interest in combining immunotherapy with radiation therapy (RT) for
      the primary treatment of locally advanced HNSCC. RT with concurrent cetuximab is
      an option for patients who are medically unfit to receive cisplatin, and ongoing
      trials seek to determine to role of cetuximab-RT in treatment de-intensification
      for HPV+ oropharyngeal HNSCC. Other ongoing trials are evaluating the use of anti
      PD-1 and anti-PD-L1 therapies in the upfront setting for newly diagnosed high
      risk, locally advanced HNSCC, in an effort to improve disease control. Finally,
      early phase I studies are now investigating the use of anti-PD-1 therapy in
      conjunction with RT for refractory recurrent or metastatic HNSCC.

PMID- 29173751
TI  - The Current State of Biological and Clinical Implications of Human Papillomavirus
      Related Oropharyngeal Cancer.
AB  - In the effort to control human papillomavirus-related oropharyngeal cancer, the
      head and neck oncology community has devoted much effort to understanding its
      disease biology and clinical behavior, and refining strategies to address early
      diagnosis and optimal management for the affected population. This review
      identifies articles published up to March 2017 on tumor biology and clinical
      implications of human papillomavirus-related oropharyngeal cancer, and summarizes
      the findings in some key areas. These include potential screening strategies,
      possible anatomical features responsible for early lymph node involvement and its
      implication for staging, biological mechanisms to explain superior outcomes
      compared to traditional nonviral-related mucosal cancers, re-appreciation of
      traditional prognostic factors (eg, hypoxia, extranodal extension, and smoking),
      and current efforts to optimize management for this patient population. The
      review reflects the global effort to mitigate the influence of this burgeoning
      disease.

PMID- 29173752
TI  - Therapeutic Implications of the Genetic Landscape of Head and Neck Cancer.
AB  - Large-scale sequencing studies of head and neck squamous cell carcinoma (HNSCC)
      have elucidated the genetic changes that characterize HNSCC. These findings have
      supported the development of therapeutic strategies that target key components of
      aberrant signaling pathways and immune dysregulation. Cumulative evidence
      suggests that these agents in combination with radiotherapy may have synergistic
      effects. This review highlights the predictive biomarkers that have been
      identified from HNSCC genomic studies and implications on the development of
      molecular-targeting agents that may effectively treat patients with HNSCC,
      especially when used in combination with radiation.

PMID- 29173753
TI  - Current Status and Future Directions of Treatment Deintensification in Human
      Papilloma Virus-associated Oropharyngeal Squamous Cell Carcinoma.
AB  - The prevalence of patients with human papilloma virus (HPV)-associated
      oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing, and it is
      now well known that these patients have a significantly better prognosis than
      patients with HPV-negative OPSCC. Though standard treatments result in excellent
      cancer control, they are also associated with substantial long-term toxicity.
      There is now great interest in evaluating less intensive (ie, deintensified)
      treatment regimens to improve the therapeutic ratio (maintain excellent cancer
      control and decrease toxicity). There are many different approaches that are
      being studied, and each have their own caveats, with varying degrees of actual
      deintensification. In this article, we critically review the current landscape of
      emerging deintensified treatment paradigms and future direction of the treatment
      of HPV-associated OPSCC.

PMID- 29173754
TI  - Molecular Imaging-Guided Radiotherapy for the Treatment of Head-and-Neck Squamous
      Cell Carcinoma: Does it Fulfill the Promises?
AB  - With the routine use of intensity modulated radiation therapy for the treatment
      of head-and-neck squamous cell carcinoma allowing highly conformed dose
      distribution, there is an increasing need for refining both the selection and the
      delineation of gross tumor volumes (GTV). In this framework, molecular imaging
      with positron emission tomography and magnetic resonance imaging offers the
      opportunity to improve diagnostic accuracy and to integrate tumor biology mainly
      related to the assessment of tumor cell density, tumor hypoxia, and tumor
      proliferation into the treatment planning equation. Such integration, however,
      requires a deep comprehension of the technical and methodological issues related
      to image acquisition, reconstruction, and segmentation. Until now, molecular
      imaging has had a limited value for the selection of nodal GTV, but there are
      increasing evidences that both FDG positron emission tomography and diffusion
      weighted magnetic resonance imaging has a potential value for the delineation of
      the primary tumor GTV, effecting on dose distribution. With the apprehension of
      the heterogeneity in tumor biology through molecular imaging, growing evidences
      have been collected over the years to support the concept of dose escalation/dose
      redistribution using a planned heterogeneous dose prescription, the so-called
      "dose painting" approach. Validation trials are ongoing, and in the coming years,
      one may expect to position the dose painting approach in the armamentarium for
      the treatment of patients with head-and-neck squamous cell carcinoma.

PMID- 29173755
TI  - Organ-Sparing in Radiotherapy for Head-and-Neck Cancer: Improving Quality of
      Life.
AB  - This is an overview of select studies characterizing the effect of radiation on
      normal tissues in the treatment of head-and-neck cancer. Recommendations for
      organ-at-risk dose constraints aiming to reduce risks of xerostomia and
      dysphagia, the factors which have the highest effect on patient quality of life,
      are discussed, along with their supporting evidence. Recent advances in
      technology and biology, and their implications for reducing toxicity are
      explored. Considerations related to organ-sparing in the setting of treatment
      deintensification for good-prognosis head-and-neck cancer are also discussed.

PMID- 29173756
TI  - Proton Therapy for Head and Neck Cancers.
AB  - Because of its sharp lateral penumbra and steep distal fall-off, proton therapy
      offers dosimetric advantages over photon therapy. In head and neck cancer, proton
      therapy has been used for decades in the treatment of skull-base tumors. In
      recent years the use of proton therapy has been extended to numerous other
      disease sites, including nasopharynx, oropharynx, nasal cavity and paranasal
      sinuses, periorbital tumors, skin, and salivary gland, or to reirradiation. The
      aim of this review is to present the physical properties and dosimetric benefit
      of proton therapy over advanced photon therapy; to summarize the clinical benefit
      described for each disease site; and to discuss issues of patient selection and
      cost-effectiveness.

PMID- 29173757
TI  - Head and Neck Cancer Survivorship: Learning the Needs, Meeting the Needs.
AB  - Cancers of the head and neck and the treatments required to control them
      frequently result in serious and persistent impairments that can affect
      participation and quality of life. Increased recognition of the needs of cancer
      survivors and their caregivers has prompted research focused on the unique
      concerns of this complex group. Unmet needs have been identified among 60-70% of
      patients and a similar proportion of their partners; impacts can include profound
      social effects, isolation, and psychiatric conditions. Interprofessional teams,
      supplementing oncology nursing and physicians with physical rehabilitation,
      occupational therapy, speech-language pathology, nutrition and psychological
      disciplines is important to address the spectrum of emotional, cognitive,
      physical and functional, and pragmatic issues. In addition to investigating
      modified anti-cancer therapy intended to reduce the frequency of long-term
      toxicities, supportive care strategies that may be effective include physical
      activity, nutritional intervention, behavioral and cognitive-behavioral therapy,
      psycho-education and goal management therapy. This article addresses identified
      needs across varied domains, the current state of research surrounding them, and
      their impact on quality of life, while also describing one cancer center's
      approach to head and neck cancer survivorship.

PMID- 29173758
TI  - Correction.

PMID- 29173759
TI  - Early detection of lung cancer using ultra-low-dose computed tomography in
      coronary CT angiography scans among patients with suspected coronary heart
      disease.
AB  - OBJECTIVES: To assess whether an additional chest ultra-low-dose CT scan to the
      coronary CT angiography protocol can be used for lung cancer screening among
      patients with suspected coronary artery disease. METHODS: 175 patients underwent
      coronary CT angiography for assessment of coronary artery disease, additionally
      undergoing ultra-low-dose CT screening to early diagnosis of lung cancer in the
      same scanner (80kVp and 15mAs). Patients presenting pulmonary nodules were
      followed-up for two years, repeating low-dose CTs in intervals of 3, 6, or 12
      months based on nodule size and growth rate in accordance with National
      Comprehensive Cancer Network guidelines. RESULTS: Ultra-low-dose CT identified 71
      patients with solitary pulmonary nodules (41%), with a mean diameter of 5.50+/
      4.00mm. Twenty-eight were >6mm, and in 79% (n=22) of these cases they were false
      positive findings, further confirmed by follow-up (n=20), resection (n=1), or
      biopsy (n=1). Lung cancer was detected in six patients due to CT screening
      (diagnostic yield: 3%). Among these, four cases could not be detected in the
      cardiac field of view. Most patients were in early stages of the disease. Two
      patients diagnosed at advanced stages died due to cancer complications. The
      addition of the ultra-low-dose CT scan represented a radiation dose increment of
      1.22+/-0.53% (effective dose, 0.11+/-0.03mSv). CONCLUSIONS: Lung cancer might be
      detected using additional ultra-low-dose protocols in coronary CT angiography
      scans among patients with suspected coronary artery disease.

PMID- 29173760
TI  - Targeting DNA damage in SCLC.
AB  - SCLC accounts for 15% of lung cancer worldwide. Characterised by early
      dissemination and rapid development of chemo-resistant disease, less than 5% of
      patients survive 5 years. Despite 3 decades of clinical trials there has been no
      change to the standard platinum and etoposide regimen for first line treatment
      developed in the 1970's. The exceptionally high number of genomic aberrations
      observed in SCLC combined with the characteristic rapid cellular proliferation
      results in accumulation of DNA damage and genomic instability. To flourish in
      this precarious genomic context, SCLC cells are reliant on functional DNA damage
      repair pathways and cell cycle checkpoints. Current cytotoxic drugs and
      radiotherapy treatments for SCLC have long been known to act by induction of DNA
      damage and the response of cancer cells to such damage determines treatment
      efficacy. Recent years have witnessed improved understanding of strategies to
      exploit DNA damage and repair mechanisms in order to increase treatment efficacy.
      This review will summarise the rationale to target DNA damage response in SCLC,
      the progress made in evaluating novel DDR inhibitors and highlight various
      ongoing challenges for their clinical development in this disease.

PMID- 29173761
TI  - Matched-pair analysis of a multi-institutional cohort reveals that epidermal
      growth factor receptor mutation is not a risk factor for postoperative recurrence
      of lung adenocarcinoma.
AB  - OBJECTIVE: It is unclear whether epidermal growth factor receptor (EGFR) mutation
      status is a risk factor for postoperative recurrence of surgically resected lung
      adenocarcinoma (ADC). Therefore, we conducted a multi-institutional study
      employing matched-pair analysis to compare recurrence-free survival (RFS) and
      overall survival (OS) of patients with lung ADC according to EGFR mutation
      status. METHODS: We collected the records of 909 patients who underwent surgical
      resection for lung ADC between 2005 and 2012 at five participating institutions
      and were also examined their EGFR mutation status. For each patient with an EGFR
      mutation, we selected one with the wild-type EGFR sequence and matched them
      according to institution, age, gender, smoking history, pathological stage
      (pStage), and adjuvant treatment. We compared RFS and OS of the matched cohort.
      RESULTS: The patients were allocated into groups (n=181 each) with mutated or
      wild-type EGFR sequences. Both cohorts had identical characteristics as follows:
      institution, median age (68 years), men (85, 47%), ever smokers (77, 43%), and
      pStage (IA, 108, 60%; IB, 48, 27%; II, 14, 8%; III, 11, 6%). The 3- and 5-year
      RFS rates of patients with mutated or wild-type EGFR sequence were 79%, 68% and
      77%, 68%, respectively (p=0.557). The respective OS rates were 92%, 81%, and 89%,
      79% (p=0.574). CONCLUSION: Matched-pair and multi-institutional analysis reveals
      that an EGFR mutation was not a significant risk factor for recurrence of
      patients with surgically resected lung adenocarcinoma.

PMID- 29173762
TI  - Quantification of plasma EGFR mutations in patients with lung cancers: Comparison
      of the performance of ARMS-Plus and droplet digital PCR.
AB  - OBJECTIVES: EGFR mutation is a key factor to predict EGFR-TKI efficacy. However,
      a significant number of advanced patients do not have sufficient tumor specimens
      for molecular testing. Also, there is a lack of quantitative assay to analyze the
      mutant abundance. This study aims to evaluate the detection efficiency and
      clinical feasibility of a new platform, namely ARMS-Plus, for the detection and
      quantification of EGFR mutations in plasma. MATERIALS AND METHODS: The detection
      limit of ARMS-Plus was assessed by detecting spiked mutant plasmids which were
      serially diluted with normal human genomic DNA. The cutoff values were defined by
      examining the mutant copy numbers presented in 134 healthy controls. Plasma
      samples from 65 lung cancer patients were collected to evaluate the clinical
      performance of ARMS-Plus. EGFR mutations were concurrently tested by droplet
      digital PCR (ddPCR) for the plasma samples and conventional amplification
      refractory mutation system-PCR (ARMS-PCR) for the matched tumor tissue specimens
      to serve as a standard for comparison. RESULTS: In this study, the analytical
      sensitivity of ARMS-Plus was 0.015%. The cutoff values of EGFR 19Del, L858R,
      T790M mutations were defined as 2, 5, and 3 copies/mL, respectively. With tumor
      specimens as the standard, the sensitivity, specificity, and concordance rate of
      ARMS-Plus and ddPCR were 60.7%, 94.6%, and 80.0%; and 50.0%, 97.3%, and 76.9%,
      respectively. For quantification, the plasma 19Del and L858R mutant abundance
      detected by ARMS-Plus and ddPCR were consistent (Spearman R=0.7956 and 0.7710,
      P<0.0001). CONCLUSION: ARMS-Plus is a reliable, convenient and cost-effective
      method for the detection and quantification of plasma EGFR mutations.

PMID- 29173763
TI  - Vasculature surrounding a nodule: A novel lung cancer biomarker.
AB  - PURPOSE: To investigate whether the vessels surrounding a nodule depicted on non
      contrast, low-dose computed tomography (LDCT) can discriminate benign and
      malignant screen detected nodules. MATERIALS AND METHODS: We collected a dataset
      consisting of LDCT scans acquired on 100 subjects from the Pittsburgh Lung
      Screening study (PLuSS). Fifty subjects were diagnosed with lung cancer and 50
      subjects had suspicious nodules later proven benign. For the lung cancer cases,
      the location of the malignant nodule in the LDCT scans was known; while for the
      benign cases, the largest nodule in the LDCT scan was used in the analysis. A
      computer algorithm was developed to identify surrounding vessels and quantify the
      number and volume of vessels that were connected or near the nodule. A
      nonparametric receiver operating characteristic (ROC) analysis was performed
      based on a single nodule per subject to assess the discriminability of the
      surrounding vessels to provide a lung cancer diagnosis. Odds ratio (OR) were
      computed to determine the probability of a nodule being lung cancer based on the
      vessel features. RESULTS: The areas under the ROC curves (AUCs) for vessel count
      and vessel volume were 0.722 (95% CI=0.616-0.811, p<0.01) and 0.676 (95% CI=0.565
      0.772), respectively. The number of vessels attached to a nodule was
      significantly higher in the lung cancer group 9.7 (+/-9.6) compared to the non
      lung cancer group 4.0 (+/-4.3) CONCLUSION: Our preliminary results showed that
      malignant nodules are often surrounded by more vessels compared to benign
      nodules, suggesting that the surrounding vessel characteristics could serve as
      lung cancer biomarker for indeterminate nodules detected during LDCT lung cancer
      screening using only the information collected during the initial visit.

PMID- 29173764
TI  - Clinical outcomes of black vs. non-black patients with locally advanced non-small
      cell lung cancer.
AB  - OBJECTIVES: The black population remains underrepresented in clinical trials
      despite reports suggesting greater incidence and deaths from locally advanced non
      small cell lung cancer (NSCLC). We determined outcomes for black and non-black
      patients in a well-annotated cohort treated with either definitive chemoradiation
      (CRT; bimodality) or CRT followed by surgery (trimodality therapy). MATERIALS AND
      METHODS: A retrospective analysis of 355 stage III NSCLC patients treated with
      curative intent at the University of Maryland, Medical Center, between January
      2000-December 2013 was performed. The Kaplan-Meier approach and the Cox
      proportional hazards models were used to analyze overall survival (OS) and
      freedom-from-recurrence (FFR) in black and non-black patients. The chi-square
      test was used to compare categorical variables. RESULTS: Black patients comprised
      42% of the cohort and were more likely to be younger (p<0.0001), male (p=0.030),
      single (p<0.0001), reside in lower household income zipcodes (p<0.0001), have an
      Eastern Cooperative Oncology Group (ECOG) performance status >0 (p<0.001), and
      less likely to undergo surgery (p<0.0001). With a median follow-up of 15 months
      for all patients and 89 months for surviving patients (range:1-186 months),
      median OS times for black and non-black patients were 22 and 24 months,
      respectively (p=0.698). FFR rates were also comparable between the two groups
      (p=0.468). Surgery improved OS in both cohorts. Race was not a significant
      predictor for OS or FFR even when adjusted for other factors. CONCLUSIONS: We
      found similar oncologic outcomes in black and non-black NSCLC patients when
      treated with curative intent in a comprehensive cancer center setting, despite
      epidemiologic differences in presentation and receipt of care. Future efforts to
      improve outcomes in black patients could focus on addressing modifiable social
      disparities.

PMID- 29173765
TI  - Esophageal ultrasound (EUS) assessment of T4 status in NSCLC patients.
AB  - BACKGROUND: Mediastinal and central large vessels (T4) invasion by lung cancer is
      often difficult to assess preoperatively due to the limited accuracy of computed
      tomography (CT) scan of the chest. Esophageal ultrasound (EUS) can visualize the
      relationship of para-esophageally located lung tumors to surrounding mediastinal
      structures. AIM: To assess the value of EUS for detecting mediastinal invasion
      (T4) of centrally located lung tumors. METHODS: Patients who underwent EUS for
      the diagnosis and staging of lung cancer and in whom the primary tumor was
      detected by EUS and who subsequently underwent surgical- pathological staging
      (2000-2016) were retrospectively selected from two university hospitals in The
      Netherlands. T status of the lung tumor was reviewed based on EUS, CT and
      thoracotomy findings. Surgical- pathological staging was the reference standard.
      RESULTS: In 426 patients, a lung malignancy was detected by EUS of which 74
      subjects subsequently underwent surgical- pathological staging. 19 patients (26%)
      were diagnosed with stage T4 based on vascular (n=8, 42%) or mediastinal (n=8,
      42%) invasion or both (n=2, 11%), one patient (5%) had vertebral involvement.
      Sensitivity, specificity, PPV and NPV for assessing T4 status were: for EUS
      (n=74); 42%, 95%, 73%, 83%, for chest CT (n=66); 76%, 61%, 41%, 88% and the
      combination of EUS and chest CT (both positive or negative for T4, (n=34); 83%,
      100%, 100% 97%. CONCLUSION: EUS has a high specificity and NPV for the T4
      assessment of lung tumors located para-esophageally and offers further value to
      chest CT scan.

PMID- 29173766
TI  - Changing costs of metastatic non small cell lung cancer in the Netherlands.
AB  - OBJECTIVES: The primary objective of this study was to identify the total
      intramural cost of illness of metastatic non-small cell lung cancer (NSCLC) in
      the Netherlands between 2006-2012. Secondary objective was to identify whether
      changes in cost patterns of metastatic NSCLC have occurred over the last years.
      METHODS: Patients diagnosed with metastatic NSCLC between 1-1-2006 and 31-12
      2012, who had follow-up to death or the date of data cut-off and no trial
      participation were included. A structured chart review was performed using a case
      report form. Data collection started after diagnosis of metastatic NSCLC and
      ended at death or April first, 2015. Data regarding outpatient visits, clinical
      attendance, oncolytic drug use, imaging, lab tests, radiotherapy and surgery were
      collected. RESULTS: Sixty-seven patients were included with a median age of 67
      years. The median follow-up was 234days. On average patients had 28 outpatient
      visits and 11 inpatient days. Oncolytic drugs were administered to 76% of the
      patients. Mean per patient expenditures amounted up to ?17,463, with oncolytic
      drugs (?6,390) as the main cost driver. In comparison with the time-period of
      2003-2005 total per patient per year expenses decreased by 44%. The contribution
      to total yearly costs of oncolytic drugs increased from 18% to 35%, while costs
      for inpatient stay decreased from 52% to 28% of total expenditures. CONCLUSION:
      Outcomes in this study demonstrate that average treatment costs for metastatic
      NSCLC in the Netherlands Cancer Institute amount to ?17,463. Compared to a prior
      study the average cost for metastatic NSCLC over time in the Netherlands has
      decreased. A shift of main cost drivers seems to have occurred from inpatient
      stay, to oncolytic drugs as main contributor. The shift towards treatment cost
      might become more visible with the introduction of immunotherapy. These results
      mark the importance of up-to-date cost of illness studies.

PMID- 29173767
TI  - Identification of a serum microRNA expression signature for detection of lung
      cancer, involving miR-23b, miR-221, miR-148b and miR-423-3p.
AB  - OBJECTIVES: Serum mircoRNAs (miRNAs), with their noticeable stability and unique
      expression pattern in patients with various diseases, are powerful novel non
      invasive biomarkers for cancer detection. The objective of this study was to
      identify specific serum miRNAs as potential diagnostic markers for detection of
      lung cancer. MATERIALS AND METHODS: The expression of serum miRNA from treatment
      naive lung cancer patients (LC), benign pulmonary disease patients (PD) and
      healthy controls (HC) were examined by PCR array. The study was divided into two
      phases: the biomarker-screening phase and the biomarker-validation phase.
      Logistic regression and receiver operating characteristics curve analyses were
      used to identify differentially expressed miRNA signatures that could distinguish
      LC from PD and HC. In addition, target genes of miRNAs were predicted using
      bioinformatic assays. RESULTS: Ten miRNAs (let-7f, miR-126-3p, miR-148b, miR-151
      5p, miR-199a-3p, miR-221, miR-23b, miR-26a, miR-27b, and miR-423-3p) in LC were
      significantly increased compared to those in PD and HC in biomarker-validation
      phase (P<0.05). Bioinformatic analyses showed that predicted targets of these
      miRNAs might have a correlation with formation and development of cancer.
      Furthermore, we have developed classifiers including 4 miRNAs (miR-23b, miR-221,
      miR-148b and miR-423-3p) that can be demonstrated as a signature for LC
      detection, yielding a receiver operating characteristic curve area of 0.885.
      CONCLUSION: our findings define a distinct miRNA expression profile in LC cases.
      These 4-miRNA signatures (miR-23b, miR-221, miR-148b and miR-423-3p) may be
      considered as novel, non-invasive biomarker for LC diagnosis.

PMID- 29173768
TI  - C-reactive protein-albumin ratio is an independent prognostic predictor of tumor
      recurrence in stage IIIA-N2 lung adenocarcinoma patients.
AB  - OBJECTIVE: To systematically evaluate the prognostic value of
      nutrition/inflammation-based markers for recurrence-free survival (RFS) in pN2
      stage IIIA lung adenocarcinoma patients. MATERIALS AND METHODS: Data from 156
      patients who had pathologically confirmed pN2-stage IIIA primary lung
      adenocarcinoma and received complete surgical resection from 2010 to 2014 were
      retrospectively analyzed. The data for Glasgow prognostic score (GPS), modified
      GPS (mGPS), high-sensitivity mGPS, C-reactive protein/albumin ratio (CAR),
      neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and prognostic
      nutritional index were analyzed. Univariate and multivariate Cox proportional
      hazards regression analyses were used to identify the prognostic factors
      associated with RFS. RESULTS: The optimal cutoff value for the CAR was set at
      0.6. A significant correlation was found between the CAR and RFS (P=0.001) by
      univariate analysis. Multivariate analysis between RFS and the factors selected
      from univariate analysis showed that ECOG performance status, pneumonectomy,
      multi-level N2, and high CAR were independent predictors of RFS. CONCLUSION: The
      CAR was the best prognostic marker to predict tumor recurrence in pN2-stage IIIA
      lung adenocarcinoma patients among the 7 nutrition/inflammation-based markers.
      The preoperative CAR may identify patients with a high risk of postoperative
      tumor recurrence.

PMID- 29173769
TI  - Durable response to osimertinib in EGFR mutated T790M wildtype non-small cell
      lung cancer with leptomeningeal metastases: A case report.
AB  - In patients with non-small cell lung cancer (NSCLC) progression with
      leptomeningeal (LM) metastases is a catastrophic event with limited treatment
      options. We report a patient who developed leptomeningeal disease while on front
      line erlotinib. High-dose tyrosine kinase inhibitor was started but ineffective.
      She was transitioned to third-generation TKI osimertinib, despite lacking a T790M
      mutation, and responded with complete resolution of symptoms and malignant
      cytology in the cerebrospinal fluid (CSF). Recent phase one data and our case
      indicate osimertinib should be viewed as a best practice for treatment of LM
      disease in epidermal growth factor receptor (EGFR) mutated NSCLC regardless of
      T790M status.

PMID- 29173770
TI  - Circulating metabolite profiles to predict overall survival in advanced non-small
      cell lung cancer patients receiving first-line chemotherapy.
AB  - OBJECTIVES: The prognosis for advanced-stage non-small cell lung cancer (NSCLC)
      is usually poor. However, survival may be variable and difficult to predict. In
      the current study, we aimed to identify circulating metabolites as potential
      predictive biomarkers for overall survival of advanced-stage (III/IV) NSCLC
      patients treated with first-line platinum-based chemotherapy. MATERIALS AND
      METHODS: Using two-stage study design, we performed global metabolomic profiling
      in blood of 220 advanced-stage NSCLC patients, including 110 with poor survival
      and 110 with good survival. Metabolomic profiling was conducted using Metabolon
      platform. The association of each metabolite with survival was assessed by Cox
      proportional hazard regression model with adjustment for covariates. RESULTS AND
      CONCLUSION: We found levels of 4 metabolites, caffeine, paraxanthine,
      stachydrine, and methyl glucopyranoside (alpha+beta), differed significantly
      between NSCLC patients with poor and good survival in both discovery and
      validation phases (P<0.05). Interestingly, majority of the identified metabolites
      are involved in caffeine metabolism, and 2 metabolites are related to coffee
      intake. In fact, caffeine metabolism pathway was the only significant pathway
      identified which significantly differed between NSCLC patients with poor and good
      survival (P=1.48E-07) in the pathway analysis. We also found 4 metabolites whose
      levels were significantly associated with good survival in both discovery and
      validation phases. Strong cumulative effects on overall survival were observed
      for these 4 metabolites. In conclusion, we identified a panel of metabolites
      including metabolites in caffeine metabolism pathway that may predict survival
      outcome in advanced-stage NSCLC patients. The identified small metabolites may be
      useful biomarker candidates to help identify patients who may benefit from
      platinum-based chemotherapy.

PMID- 29173771
TI  - Genetic predisposition to lung adenocarcinoma among never-smoking Chinese with
      different epidermal growth factor receptor mutation status.
AB  - OBJECTIVES: The inconsistent findings from genetic association studies may be
      related to the heterogeneity in different molecular subtypes of lung cancer. This
      study evaluated the predisposing single-nucleotide polymorphisms (SNPs) in
      epidermal growth factor receptor (EGFR) mutant and EGFR wild-type lung
      adenocarcinoma separately among never-smokers. MATERIALS AND METHODS: This was a
      two-stage case-control study. Never-smokers with pathologically confirmed lung
      adenocarcinoma and healthy controls were recruited in Hong Kong and Macau.
      Genomic DNA was extracted and genotyped by MassARRAY. In the discovery stage, 51
      SNPs were investigated at the SNP, gene and pathway level among 103 EGFR mutant
      and 78 EGFR wild-type lung adenocarcinoma cases compared with matched controls.
      In the validation stage, SNPs that were identified with significant lung cancer
      risk were replicated in a separate cohort of 84 lung adenocarcinoma cases and
      compared with 103 Chinese Han, Beijing and 105 Chinese Han, Southern public
      controls from the 1000 genome database. RESULTS AND CONCLUSION: The genetic
      association of IL-6 rs2069840 with EGFR mutant lung adenocarcinoma was
      ascertained. In the discovery stage, haplotype GGG in three SNPs (rs2069840,
      rs2069852, rs2066992) of IL-6, synergetic effects of IL-6 rs2069840 and
      environmental tobacco smoke in the workplace were found to be related to EGFR
      mutant lung adenocarcinoma. ERCC2 rs238406 showed a marginally significant
      association with EGFR mutant lung adenocarcinoma in the validation stage
      (P=0.096). ERCC2 rs50871 and ATM rs611646 showed significant association with
      EGFR wild-type lung adenocarcinoma in the discovery stage. In conclusion, IL-6
      rs2069840 conferred susceptibility to EGFR mutant lung adenocarcinoma in a Hong
      Kong and Macau never-smoking Chinese population.

PMID- 29173772
TI  - Clinical characteristics and sequence complexity of anaplastic lymphoma kinase
      gene fusions in Chinese lung cancer patients.
AB  - OBJECTIVES: To investigate the clinical characteristics of anaplastic lymphoma
      kinase (ALK) rearrangements and sequence complexity of the ALK fusion gene in
      Chinese lung cancer patients. METHODS: We prospectively screened ALK
      rearrangements in 1474 lung cancer specimens, including 1387 cases of non-small
      cell lung cancer (NSCLC), 54 cases of small cell lung cancer (SCLC), and 33 cases
      of cancer with lung metastasis from other organs by both standard polymerase
      chain reaction (PCR) and rapid amplification of cDNA ends (RACE)-coupled PCR.
      Fifteen cases of ALK-positive RACE-coupled PCR products were transformed into
      Escherichia coli for molecular cloning and sequenced for complexity analysis.
      RESULTS: The overall frequency of ALK rearrangements was 5.1% (71/1387) in NSCLC.
      In 71 positive cases, the coexistence of epidermal growth factor receptor (EGFR)
      and ALK variations was found in 6 cases (8.5%), and the coexistence of different
      ALK variants was found in 2 cases (2.8%) (1 case with variants 1 and 9; the other
      case with variants 3 and 2) by PCR analysis. Furthermore, through sequence
      cloning analysis of 15 cases of non-selective ALK-positive samples, two cases
      with variants 1 and 3 harbored the coexistence of three subtypes (variant 1
      subtypes: E13; A20, E13del63; A20 and E7E12E13; A20 and variant 3 subtypes: E6;
      A20, E6ins33; A20 and E3E6; A20). Variant 3a and 3b subtypes were always
      coexistent and had the same proportion of ALK variant 3 rearrangements. ALK
      rearrangement was associated with young age, female gender, never-smokers, those
      with adenocarcinoma, advanced stage, and EGFR mutations. No ALK fusion was
      detected in 54 cases of SCLC or 33 cases of cancer with lung metastasis from
      other organs. CONCLUSIONS: The identification of novel ALK variants, the
      coexistence of EGFR mutations and ALK fusions, the coexistence of ALK variants,
      and the coexistence of subtypes reveal the diversity and sequence complexity of
      ALK fusions.

PMID- 29173774
TI  - Audacious Goals - 2.0 The Global Initiative for Children's Surgery.
AB  - This is the Presidential Address given at the 48th Annual Meeting of the American
      Pediatric Surgical Association (APSA) held in Hollywood, Florida, from May 4-7,
      2017.

PMID- 29173773
TI  - A comprehensive review of uncommon EGFR mutations in patients with non-small cell
      lung cancer.
AB  - INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) harboring uncommon
      epidermal growth factor receptor (EGFR) mutations are a heterogeneous group
      exhibiting differential responses to EGFR inhibitors. This retrospective study
      reviews the prevalence of uncommon EGFR mutations in a Chinese NSCLC cohort and
      the clinical characteristics and efficacy of EGFR tyrosine kinase inhibitors
      (TKIs) associated with these patients. MATERIALS ANDMETHODS: A total of 5363 lung
      cancer patients were screened and underwent EGFR genotyping at the Guangdong Lung
      Cancer Institute. Of those with uncommon EGFR mutations, the clinical
      characteristics and responses to EGFR-TKIs were reviewed retrospectively.
      RESULTS: Uncommon EGFR mutations were observed in 218 patients, comprising 11.9%
      of all patients with documented EGFR mutations. More smokers (30.7% vs. 24.3%,
      P=0.039) and males (54.1% vs. 44.4%, P=0.007) were among the patients with
      uncommon mutations compared with common mutations. The most frequent uncommon
      mutations were exon 20 insertions (30.7%, n=67), followed by G719X mutations
      (21.1%, n=46) and compound L858R mutations (17.0%, n=37). Favorable efficacy was
      observed in patients harboring compound L858R or G719X mutations, with a median
      progression-free survival (PFS) of 15.2 (95% CI: 8.7-21.7) or 11.6 (95% CI: 3.6
      19.6) months, respectively. The median PFS of those with the T790M mutation or an
      exon 20 insertion was 1.0 (95% CI: 0.0-2.2) and 3.0 (95% CI: 1.3-4.7) months,
      respectively. CONCLUSION: This study reviewed the prevalence of uncommon EGFR
      mutations and their sensitivity to EGFR-TKIs. Favorable responses were observed
      in patients with G719X and compound L858R mutations, indicating that they may
      benefit from EGFR-TKIs as a first-line therapy.

PMID- 29173775
TI  - Comparison of early versus delayed strategies for repair of congenital
      diaphragmatic hernia on extracorporeal membrane oxygenation.
AB  - PURPOSE: For the last seven years, our institution has repaired infants with CDH
      that require ECMO early after cannulation. Prior to that, we attempted to
      decannulate before repair, but repaired on ECMO if we were unable to wean after
      two weeks. This study compares those strategies. METHODS: From 2002 to 2016, 65
      infants with CDH required ECMO. 67.7% were repaired on ECMO, and 27.7% were
      repaired after decannulation. Data were compared between patients repaired
      <=5days after cannulation ("early protocol", n=30) and >5days after cannulation
      or after de-cannulation ("late protocol", n=35). We used Cox regression to assess
      differences in outcomes between groups. RESULTS: Survival for the early and late
      protocol groups was 43.3% and 68.8%, respectively (p=0.0485). For patients that
      were successfully decannulated before repair, survival was 94.4%. Moreover, the
      early repair protocol was associated with prolongation of ECMO (16.8+/-7.4 vs.
      12.6+/-6.8days, p=0.0216). After multivariate regression, the early repair
      protocol was an independent predictor of both mortality (HR=3.48, 95% CI=1.28
      9.45, p=0.015) and days on ECMO (IRR=1.39, 95% CI=1.07-1.79, p=0.012). All
      bleeding occurred in patients repaired on ECMO (29.5%, 13/44). CONCLUSIONS: Our
      data suggest that protocolized CDH repair early after ECMO cannulation may be
      associated with increased mortality and prolongation of ECMO. However, early
      repair is not necessarily harmful for those patients who would otherwise be
      unable to wean from ECMO before repair. Further work is needed to better move
      towards individualized patient care. TYPE OF STUDY: Treatment Study. LEVEL OF
      EVIDENCE: Level III.

PMID- 29173776
TI  - Out of Africa: Insights from a prospective pediatric surgery database.
AB  - In this year's Robert E. Gross lecture, I describe how experiences early in my
      career at a government referral hospital in Banjul, The Gambia, influenced my
      research. Collecting prospective data on all children presenting to the hospital
      with surgical problems allowed me to gain an understanding of the epidemiology of
      childhood surgical conditions in sub-Saharan Africa and an appreciation for the
      inherent challenges of delivering surgical care in settings of limited resources.
      Based on findings from this database, my research over the past 20years has
      focused on developing strategies for improving surgical care in low-income
      countries and better understanding the geographical variations that occur in some
      of the most common surgical conditions in high-income countries (e.g.,
      appendicitis). Although this research continues to be a work-in-progress, it has
      the potential to improve the surgical care of children in both high- and low
      income countries. Much of this research would not have been possible had I not
      ventured off the usual path for an academic surgeon.

PMID- 29173777
TI  - Surgical excision is the treatment of choice for cervical lymphatic malformations
      with mediastinal expansion.
AB  - BACKGROUND: Lymphatic malformations (LMs) in the mediastinum are uncommon.
      However, cervical LMs may expand into the mediastinum. The aim of this study was
      to review our experience with the management of patients with LMs involving the
      mediastinum and to propose a treatment algorithm to guide the management of these
      rare malformations. MATERIAL AND METHODS: This was a descriptive retrospective
      chart review of all patients with LMs involving the mediastinum treated at our
      Institution between 2009 and 2015. We collected demographic data, data on
      investigations, management, and complications of the treatment, as well as
      outcomes at follow-up. Complications were defined and described according to the
      Clavien-Dindo classification. The clinical outcome was assessed using a clinical
      assessment scale. RESULTS: The cohort consisted of seven patients. Airway
      compromise at the time of diagnosis was seen in 4 patients. Three patients had
      anatomical compression of the trachea and two patients had sub-total compression
      of the right lung. All three patients with tracheoscopy-verified compression of
      the trachea had compromise of the distal trachea, and a tracheostomy would not
      have been protective. All patients received sclerotherapy. The median time with
      mechanical ventilation at the neonatal intensive care unit after each
      sclerotherapy was eleven days (range 8-31). Each patient received sclerotherapy
      in median three times (range 1-9). Five of the patients (71%) were operated with
      excision of the LM in the mediastinum. Two of the patients were operated
      primarily and three patients were operated after major complications to
      sclerotherapy. The patients treated with sclerotherapy and the operated patients
      had comparable amount of mild complications, Clavien-Dindo grade I-II
      complications. Severe complications, Clavien-Dindo grade III-IV, were seen five
      times more commonly after sclerotherapy than after surgery. The clinical outcome
      was excellent for the operated patients and fair to good for the patients
      receiving only sclerotherapy. CONCLUSION: Patients with cervical LM involving the
      mediastinum represent a high-risk group with respect to the severity of
      complications following sclerotherapy. The swelling is unpredictable and requires
      extended observation at an intensive care unit with ventilation support.
      Tracheostomy does not prevent tracheal compression in mediastinal LM, as the
      malformation may compress trachea distal to the stoma. Surgical resection of the
      LM in the mediastinum is recommended, with the possibility of intra-operative
      sclerotherapy as an adjunctive. LEVEL OF EVIDENCE: IV.

PMID- 29173778
TI  - Assessing the long term manometric outcomes in patients with previous
      laparoscopic anorectoplasty (LARP) and posterior sagittal anorectoplasty (PSARP).
AB  - BACKGROUND/PURPOSE: The objective of this study is to compare the long term
      manometric outcomes in patients with previous laparoscopic anorectoplasty (LARP)
      and posterior sagittal anorectoplasty (PSARP). METHODS: This is a single-centered
      retrospective study and the participants were born with various types of
      anorectal malformation. Manometric assessment was carried out with high
      resolution anorectomanometry performed as a day procedure. In addition, a seven
      itemed bowel function score (BFS) was utilized to assess the functional outcomes.
      RESULTS: A total of 30 patients were included in this study (PSARP=14, LARP=16)
      and the median follow up periods were 15.5years and 9years in the PSARP and LARP
      groups respectively (p=0.06). The median value of BFS was significantly lower in
      the PSARP group (PSARP=12.5, range: 8-18; LARP=16, range: 10-20, p=0.03). The
      median value of sphincteric resting pressure was 20mmHg (range: 10-50mmHg) in the
      PSARP group and 40mmHg (range: 10-70mmHg) in the LARP group (p=0.05). There was
      no significant difference in following measurements: the percentage of patient
      having a normal sphincteric resting pressure (PSARP vs LARP=50% vs 75%, p=0.28);
      the median sphincteric squeeze pressure (PSARP vs LARP=30mmHg, range: 10-100 vs
      50mmHg, range: 20-140mmHg, p=0.08); the incidence of rectoanal inhibitory reflex
      (RAIR) (PSARP vs LARP=42.9% vs 31.3%, p=0.14) and the median value for volume of
      air to elicit the first anal sensation (PSARP vs LARP=30ml, range: 20-60ml vs
      40ml, range: 20-80ml, p=0.18). CONCLUSION: Anorectomanometry is a useful follow
      up study after anorectoplasty and majority of the patients with previous LARP
      could retain a normal sphincteric resting pressure during long term follow up.
      Comparing the two surgical approaches, patients with previous LARP could achieve
      a higher bowel function score as well as sphincter resting pressure in manometric
      assessment. LEVEL OF EVIDENCE: Level III.

PMID- 29173779
TI  - Development of Drug Therapies for Newborns and Children: The Scientific and
      Regulatory Imperatives.
AB  - Pediatric legislation has generated information about the efficacy, safety, and
      dosing of more than 600 products in children. Extrapolation of adult efficacy
      data has been an integral part of pediatric drug development. Advances in our
      understanding of physiology and pharmacology have improved the approach to
      pediatric dose selection. However, a high percentage of pediatric trials do not
      meet their primary efficacy endpoint. Delays in initiating completing pediatric
      studies persist. This article describes these advances and provides innovative
      approaches to optimize pediatric drug development.

PMID- 29173780
TI  - Approaching Current and New Drug Therapies for Pediatric Asthma.
AB  - As new therapies for pediatric asthma are approved by the Food and Drug
      Administration, clinicians should be aware of their benefits and limitations.
      Accompanying these therapies are potential obstacles, including the delivery of
      inhaled therapies and age-specific issues regarding implementation and adherence.
      New insights are being added to well-established controller medications,
      including inhaled corticosteroids and long-acting beta-agonists, while new
      medications previously approved in adults, including tiotropium and biologics,
      are now being evaluated for use in children. These drugs can be useful additive
      therapies to treat patients who are currently not responding to guidelines-based
      therapy.

PMID- 29173781
TI  - Psychopharmacology of Bipolar Disorders in Children and Adolescents.
AB  - Bipolar disorder is a debilitating illness that often leads to functional
      impairment when untreated. Monotherapy with mood stabilizers is preferable,
      although combination therapy may be necessary in refractory cases. Most studies
      focus on the use of lithium, anticonvulsants, and second-generation
      antipsychotics in the treatment of acute manic or depressive phases, as well as
      maintaining adequate response after the episode. More research is needed in the
      area of psychopharmacology of pediatric bipolar disorder to bridge the gap
      between clinical needs and the available data.

PMID- 29173782
TI  - New Psychoactive Substances in Pediatric Patients.
AB  - New psychoactive substances (NPS), namely cannabinoids, cathinones, and opioids,
      have surged in popularity among school-age children, resulting in serious
      morbidity and mortality globally. In the last decade, there has been a rapid
      evolution of NPS resulting in hundreds of new compounds. Little to no evidence
      for humans is available on most compounds. The clinical presentations of patients
      intoxicated with cannabinoids and cathinones are highly variable but most
      commonly present with a sympathomimetic toxidrome, for example, agitation,
      delirium, and tachycardia. Those with opioids present with a classic opioid
      toxidrome: coma, dilated pupils, and respiratory failure.

PMID- 29173783
TI  - Dietary Supplements in Children.
AB  - High-quality systematic reviews of use of herbal or homeopathic remedies in
      children often suffer from design flaws, such as not following PRISMA guidelines,
      inconsistent outcome measurements, and paucity of high-quality studies. Herbal
      remedies have modest demonstrated benefits with insufficient evidence to
      recommend any particular supplement. Homeopathic remedies have no role in
      treatment of pediatric conditions, and have been associated with great harm in
      infants given homeopathic teething products. Two types of herbal supplements are
      associated with high risk in adolescents, energy drinks and adulterated weight
      loss products. Parents should be counseled about risks of these products.

PMID- 29173784
TI  - Anticoagulation Therapies in Children.
AB  - Venous thromboembolism is occurring with increasing frequency in children
      resulting in the more widespread use of anticoagulation in pediatrics.
      Antithrombotic drugs in children can be divided into the standard and alternative
      agents. This review discusses standard and alternative anticoagulants. Because
      standard anticoagulants have significant limitations, including variable
      pharmacokinetics, issues with therapeutic drug monitoring, frequency of
      administration, efficacy, and adverse effects, it is expected that the use of
      alternative anticoagulants will increase over time. With their improved
      properties and recent prospective clinical trial data, the current and future use
      of these agents will likely slowly replace of the standard anticoagulants.

PMID- 29173785
TI  - Probiotics in Newborns and Children.
AB  - Microbes and humans have been closely associated throughout evolution; this
      symbiotic and/or commensal relationship is crucial for normal development and
      health. The use of probiotics has been the topic of intense investigation in the
      past couple of decades because they have the capability to promote health. Based
      on these studies, it can be debated whether they are being used to promote
      overall health or to treat and prevent diseases. This review provides an overview
      and analysis of evidence about what is currently known about the health benefits
      of these agents that are marketed for use in children and neonates.

PMID- 29173786
TI  - Drug Treatment of Seizures and Epilepsy in Newborns and Children.
AB  - The mainstay of treatment of childhood epilepsy is to administer antiepileptic
      drugs (AEDs). This article provides an overview of the clinical approach to drug
      treatment of childhood epilepsy, focusing on general principles of therapy and
      properties of recently introduced medications. Initiation and cessation of
      therapy, adverse medication effects, drug interactions, indications for the
      various AEDs, and off-label use of AEDs are reviewed. The distinct challenges in
      treatment of epileptic spasms and neonatal seizures are addressed. Finally, ideas
      for the future of drug treatment of childhood epilepsy are presented, with
      particular attention to precision medicine.

PMID- 29173787
TI  - Therapeutic Drug Monitoring in Inflammatory Bowel Disease: History and Future
      Directions.
AB  - Clinical trials for the most effective drugs in the armamentarium of medications
      for inflammatory bowel disease (IBD) have shown only a 50-60% response rate, and
      this drops to 30% in maintenance. However, therapeutic drug monitoring (TDM) to
      adjust dosing to account for patient-specific characteristics, which has been
      shown to improve outcomes, was not utilized in these trials. This review will
      detail the development of TDM within the IBD space as it evolved from thiopurines
      to biologics and continues to evolve with loftier treat-to-target goals and more
      sophisticated dashboard systems.

PMID- 29173788
TI  - Non-steroidal Anti-inflammatory Drugs in Newborns and Infants.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen are used in young
      infants and newborns for pain and fever control, patent ductus closure,
      prevention of intraventricular hemorrhage, and potentially for prevention of
      retinopathy of prematurity. These drugs inhibit cyclooxygenase 1 (COX-1), COX-2,
      and peroxidases, thus, blocking prostaglandin (PG) synthesis. PGs are eicosanoids
      that regulate several physiologic, pathologic, and cellular processes, including
      vasomotor tone, platelet aggregation, sensitization of neurons to pain, and many
      molecular events critical to physiologic homeostasis. NSAIDs inhibit caspases and
      cell death. Increasing knowledge of these molecular entities may allow targeted
      drug development to prevent or minimize neonatal morbidities.

PMID- 29173789
TI  - Metformin Use in Children and Adolescents with Prediabetes.
AB  - With the increasing incidence of childhood obesity, clinicians need to understand
      its comorbidities and their management. The American Diabetes Association
      recommends pediatricians screen high-risk overweight and obese children.
      Identifying and treating prediabetic children and adolescents can help to reduce
      the burden of type 2 diabetes. Lifestyle interventions are pivotal. Metformin is
      the only oral medication approved for diabetes treatment in children. It has been
      studied in clinical trials in nondiabetic children and has been shown to have
      beneficial effects on body weight. Effects on diabetes prevention have not been
      studied and long-term data are limited in the pediatric population.

PMID- 29173790
TI  - Inhaled Drugs and Systemic Corticosteroids for Bronchopulmonary Dysplasia.
AB  - All definitions of bronchopulmonary dysplasia (BPD) have limitations and a new
      definition for the purpose of clinical research, benchmarking, and prognostic
      prediction is needed. Different inhaled and systemic drugs are currently used to
      prevent or treat BPD. Despite some positive effects on BPD, more information
      about the effects of inhaled corticosteroids is required to assess overall
      efficacy and associated risks. One needs to balance the risks of
      neurodevelopmental impairment owing to systemic corticosteroids against those of
      BPD itself. Future studies should, therefore, focus on infants with a very high
      risk of developing BPD and include pharmacokinetics and long-term developmental
      outcomes.

PMID- 29173791
TI  - New Antimicrobial Agents for the Treatment of Staphylococcal Infections in
      Children.
AB  - Several new antimicrobial agents-daptomycin, ceftaroline, telavancin,
      dalbavancin, and-tedizolid have been approved for the treatment of staphylococcal
      infections, including methicillin-resistant Staphylococcus aureus (MRSA), in
      adults. Ceftaroline and daptomycin have been approved by the US Food and Drug
      Administration for use in children. Ceftaroline, a beta-lactam antibiotic with
      activity against MRSA, has been approved for treatment of community-acquired
      bacterial pneumonia and complicated skin and skin structure infections.
      Daptomycin has been approved for treatment of complicated skin and skin structure
      infections. In this article, we review the pharmacokinetics and pharmacodynamics
      of these antibiotics and available data on use in children.

PMID- 29173792
TI  - Antifungal Drugs in Newborns and Children.
AB  - Invasive fungal infections are a significant cause of morbidity and mortality in
      infants and children. Early diagnosis is critical, and treatment with the
      appropriate drug and dose should be initiated promptly. Although an increasing
      number of studies have examined dosing of antifungals in this population,
      pediatric safety and efficacy data are lacking.

PMID- 29173793
TI  - Antiviral Drugs in Newborn and Children.
AB  - This article focuses on the clinically relevant approved antiviral medications
      available for the treatment of infants and children. A brief overview of drug
      categories, mechanism of action, resistance, pharmacokinetics, and side effects
      is provided for the more commonly prescribed antivirals. The patient categories
      addressed are treatment and prophylaxis of influenza, neonatal herpes simplex
      virus and congenital cytomegalovirus, treatment and prophylaxis of viral disease
      in the immunocompromised host, and a brief introduction to the antivirals
      available to treat hepatitis B and hepatitis C in children.

PMID- 29173794
TI  - Drug Dosing in Obese Children: Challenges and Evidence-Based Strategies.
AB  - With the alarming increase of obesity in children, pediatricians are increasingly
      being confronted with difficult dosing decisions. Many drug labels do not provide
      specific dosing instructions for children who are obese. In this article, we
      describe the physiologic parameters altered by obesity and their influences on
      drug disposition and effect. We review the principles of allometry, and the key
      pharmacokinetic parameters that can be used to derive age appropriate dosing
      regimens. Last, we illustrate how appropriate weight descriptors can be selected,
      and how important PK parameters can be extrapolated for dosing in obese children
      when pediatric pharmacokinetic information is available.

PMID- 29173795
TI  - Evolution of Pharmacotherapeutics and Pharmacotoxidromes in Newborns and
      Children: Progress and Challenges.

PMID- 29173796
TI  - The Perils of Predatory Publishing: Views and Advice from an Editor and a Health
      Sciences Librarian.

PMID- 29173797
TI  - The Effects of Massage Therapy on Pain and Anxiety after Surgery: A Systematic
      Review and Meta-Analysis.
AB  - Pain management is critical for patients after surgery, but current pain
      management methods are not always adequate. Massage therapy may be a therapeutic
      complementary therapy for pain. Many researchers have investigated the effects of
      massage therapy on post-operative pain, but there have been no systematic reviews
      and meta-analysis of its efficacy for post-operative patients. Our objective was
      to assess the effects of massage therapy on pain management among post-operative
      patients by conducting a systematic review and meta-analysis. The databases
      searched included MEDLINE, CINAHL, and the Cochrane Library's CENTRAL. To assess
      the effects of massage therapy on post-operative pain and anxiety, we performed a
      meta-analysis and calculated standardized mean difference with 95% CIs
      (Confidential Intervals) as a summary effect. Ten randomized controlled trials
      were selected (total sample size = 1,157). Meta-analysis was conducted using
      subgroup analysis. The effect of single dosage massage therapy on post-operative
      pain showed significant improvement (-0.49; 95% confidence intervals -0.64, 
      0.34; p < .00001) and low heterogeneity (p = .39, I2 = 4%), sternal incisions
      showed significant improvement in pain (-0.68; -0.91, -0.46; p< .00001) and low
      heterogeneity (p = .76, I2 = 0%). The anxiety subgroups showed substantial
      heterogeneity. The findings of this study revealed that massage therapy may
      alleviate post-operative pain, although there are limits on generalization of
      these findings due to low methodological quality in the reviewed studies.

PMID- 29173798
TI  - Portable CT Pulmonary Angiogram in an Infant on Veno-Arterial Extracorporeal
      Membrane Oxygenation in the Pediatric Intensive Care Unit.
AB  - PURPOSE: Computed tomography (CT) has been shown to change management in children
      on extracorporeal membrane oxygenation (ECMO). Although techniques have been
      described to transport these critically ill patients to the CT suite in the
      radiology department, transport out of the intensive care setting is not without
      risk, and using portable CT is a practical alternative. However, obtaining a CT
      pulmonary angiogram (CTPA) in a patient on veno-arterial (VA) ECMO presents
      unique challenges due to bypass of the cardiopulmonary system, which may lead to
      suboptimal opacification of the pulmonary arteries. METHODS: We describe a method
      to obtain a diagnostic CTPA study in an infant on VA ECMO in the intensive care
      unit using portable CT. Our solution involved temporary withholding ECMO and
      using the venous cannula to deliver a compact contrast bolus to the right atrium
      to adequately opacify the pulmonary arteries. Special attention was given to the
      delivery of the contrast bolus, which was given by hand injection, to ensure it
      coincided with image acquisition and minimized the time ECMO was withheld.
      RESULTS: We were able to successfully obtain a diagnostic CTPA study in an infant
      on VA ECMO in the intensive care unit using portable CT. CONCLUSION: This case
      demonstrates that in select instances CTPA in infants on VA ECMO can be achieved
      using a portable CT system.

PMID- 29173799
TI  - Microtubule-Organizing Centers: Towards a Minimal Parts List.
AB  - Despite decades of molecular analysis of the centrosome, an important microtubule
      organizing center (MTOC) of animal cells, the molecular basis of microtubule
      organization remains obscure. A major challenge is the sheer complexity of the
      interplay of the hundreds of proteins that constitute the centrosome. However,
      this complexity owes not only to the centrosome's role as a MTOC but also to the
      requirements of its duplication cycle and to various other functions such as the
      formation of cilia, the integration of various signaling pathways, and the
      organization of actin filaments. Thus, rather than using the parts lists to
      reconstruct the centrosome, we propose to identify the subset of proteins
      minimally needed to assemble a MTOC and to study this process at non-centrosomal
      sites.

PMID- 29173801
TI  - Corrigendum to ''Preserving privacy of online digital physiological signals using
      blind and reversible steganography'' [Computer Methods and Programs in
      Biomedicine 151C (2017) 159-170].

PMID- 29173800
TI  - Zebrafish Infection: From Pathogenesis to Cell Biology.
AB  - The study of host-pathogen interactions has illuminated fundamental research
      avenues in both infection and cell biology. Zebrafish (Danio rerio) larvae are
      genetically tractable, optically accessible, and present a fully functional
      innate immune system with macrophages and neutrophils that mimic their mammalian
      counterparts. A wide variety of pathogenic bacteria have been investigated using
      zebrafish models, providing unprecedented resolution of the cellular response to
      infection in vivo. In this review, we illustrate how zebrafish models have
      contributed to our understanding of cellular microbiology by providing an in vivo
      platform to study host-pathogen interactions from the single cell to whole animal
      level. We also highlight discoveries made from zebrafish infection that hold
      great promise for translation into novel therapies for humans.

PMID- 29173802
TI  - White blood cells identification system based on convolutional deep neural
      learning networks.
AB  - BACKGROUND AND OBJECTIVES: White blood cells (WBCs) differential counting yields
      valued information about human health and disease. The current developed
      automated cell morphology equipments perform differential count which is based on
      blood smear image analysis. Previous identification systems for WBCs consist of
      successive dependent stages; pre-processing, segmentation, feature extraction,
      feature selection, and classification. There is a real need to employ deep
      learning methodologies so that the performance of previous WBCs identification
      systems can be increased. Classifying small limited datasets through deep
      learning systems is a major challenge and should be investigated. METHODS: In
      this paper, we propose a novel identification system for WBCs based on deep
      convolutional neural networks. Two methodologies based on transfer learning are
      followed: transfer learning based on deep activation features and fine-tuning of
      existed deep networks. Deep acrivation featues are extracted from several pre
      trained networks and employed in a traditional identification system. Moreover, a
      novel end-to-end convolutional deep architecture called "WBCsNet" is proposed and
      built from scratch. Finally, a limited balanced WBCs dataset classification is
      performed through the WBCsNet as a pre-trained network. RESULTS: During our
      experiments, three different public WBCs datasets (2551 images) have been used
      which contain 5 healthy WBCs types. The overall system accuracy achieved by the
      proposed WBCsNet is (96.1%) which is more than different transfer learning
      approaches or even the previous traditional identification system. We also
      present features visualization for the WBCsNet activation which reflects higher
      response than the pre-trained activated one. CONCLUSION: a novel WBCs
      identification system based on deep learning theory is proposed and a high
      performance WBCsNet can be employed as a pre-trained network.

PMID- 29173803
TI  - 1H-detected MAS solid-state NMR experiments enable the simultaneous mapping of
      rigid and dynamic domains of membrane proteins.
AB  - Magic angle spinning (MAS) solid-state NMR (ssNMR) spectroscopy is emerging as a
      unique method for the atomic resolution structure determination of native
      membrane proteins in lipid bilayers. Although 13C-detected ssNMR experiments
      continue to play a major role, recent technological developments have made it
      possible to carry out 1H-detected experiments, boosting both sensitivity and
      resolution. Here, we describe a new set of 1H-detected hybrid pulse sequences
      that combine through-bond and through-space correlation elements into single
      experiments, enabling the simultaneous detection of rigid and dynamic domains of
      membrane proteins. As proof-of-principle, we applied these new pulse sequences to
      the membrane protein phospholamban (PLN) reconstituted in lipid bilayers under
      moderate MAS conditions. The cross-polarization (CP) based elements enabled the
      detection of the relatively immobile residues of PLN in the transmembrane domain
      using through-space correlations; whereas the most dynamic region, which is in
      equilibrium between folded and unfolded states, was mapped by through-bond INEPT
      based elements. These new 1H-detected experiments will enable one to detect not
      only the most populated (ground) states of biomacromolecules, but also sparsely
      populated high-energy (excited) states for a complete characterization of protein
      free energy landscapes.

PMID- 29173804
TI  - Coagulation profile following liver resection: Does liver cirrhosis affect
      thromboelastography?
AB  - BACKGROUND: Thromboelastography has called into question the coagulopathy seen
      following partial hepatectomy. However the coagulation profile in cirrhotic
      livers has not been studied. Our objective was to determine the coagulation
      profile following partial hepatectomy in normal and cirrhotic livers. METHODS:
      Patients undergoing liver resection were prospectively enrolled in the study. The
      prothrombin time and international normalized ratio, as well as the
      thromboelastogram, were obtained preoperatively, post-operatively, and on post
      operative days 1, 3, and 5. RESULTS: 22 noncirrhotic and 11 cirrhotic patients
      undergoing liver resection were enrolled. Postoperatively the thromboelastogram
      demonstrated a hypercoagulable profile in 64%, 33%, 39% and 36% of patients on
      post-operative days 0, 1, 3 and 5 respectively. There was no difference between
      patients with cirrhosis and those without underlying liver disease. CONCLUSION:
      Patients appear to have a similar coagulation profile after liver resection
      regardless of underlying cirrhosis with many having a hypercoagulable profile.

PMID- 29173805
TI  - Cardiac Amyloidosis: An Updated Review With Emphasis on Diagnosis and Future
      Directions.
AB  - Cardiac amyloidosis occurs because of abnormal protein (amyloid) deposition in
      the cardiac tissue. Even with advanced diagnostic techniques and treatments, the
      prognosis of amyloidosis remains poor. The diagnosis of cardiac amyloidosis
      particularly needs to be in the differential in patients presenting with heart
      failure with preserved ejection fraction. This entity remains underdiagnosed due
      to lack of suspicion on the part of many clinicians. Involvement of cardiac
      tissue is the utmost determinant factor for available treatment options and
      prognosis. Many cases of cardiac amyloidosis usually remain undiagnosed or
      diagnosed only in advanced stages when treatment options are limited and
      associated with poor survival. Hence, early recognition of cardiac amyloidosis is
      indispensable in halting the disease process before irreversible changes occur.
      The purpose of this review is to summarize the recent updates in the evaluation
      and management of cardiac amyloidosis and to discuss potential future treatments
      options.

PMID- 29173806
TI  - Cerebral ring enhancing lesion with diffusion restriction in a South American
      patient.

PMID- 29173807
TI  - Association between hemostatic markers, serum lipid fractions and progression of
      cerebral small vessel disease: A 2-year follow-up study.
AB  - INTRODUCTION: Little is known if hemostatic markers and serum lipid fractions can
      predict further radiological progression beyond vascular risk factors in cerebral
      small vessel disease (SVD). We investigated whether they are associated with SVD
      radiological progression and if they are related to different SVD clinical
      manifestations. METHODS: A single-center, prospective, cohort study with 2 years
      of radiological follow-up was performed in consecutive patients with different
      SVD manifestations. The study group consisted of 123 patients: 49 with lacunar
      stroke (LS), 48 with vascular dementia (VaD) and 26 with vascular parkinsonism
      (VaP). We assessed SVD progression by a visual SVD scale. We determined the
      relationship between serum or plasma concentrations of tissue factor (TF),
      thrombomodulin, beta-thromboglobulin (BTG), fibrinogen, D-dimer and total
      cholesterol, HDL-C, LDL-C, triglycerides and SVD progression by logistic
      regression analysis. RESULTS: 34.9% patients had SVD radiological progression:
      43% had isolated WMLs progression, 23.2% had new lacunes, 34.8% had both WMLs
      progression and new lacunes. Fibrinogen [OR 1.02 (95% CI 1.006-1.011] was
      significantly associated with risk of new lacunes or WMLs progression regardless
      of the clinical SVD manifestation. While low HDL [OR 0.96 (0.93-1)] and TF [OR
      1.07 (0.99-1.1)] were marginally associated with new lacunes, BTG [OR 1.005 (0.99
      1.01)] was associated with WMLs progression. CONCLUSION: We found a relationship
      between fibrinogen and risk of radiological progression of SVD regardless of the
      clinical SVD manifestation. In addition, lower HDL and increased TF predicted
      development of new lacunes, and higher BTG was associated with risk of WMLs
      progression.

PMID- 29173808
TI  - Epigenetic and microenvironmental alterations in bone marrow associated with ROS
      in experimental aplastic anemia.
AB  - Aplastic anemia or bone marrow failure often develops as an effect of
      chemotherapeutic drug application for the treatment of various pathophysiological
      conditions including cancer. The long-term bone marrow injury affects the basic
      hematopoietic population including hematopoietic stem/progenitor cells (HSPCs).
      The present study aimed in unearthing the underlying mechanisms of
      chemotherapeutics mediated bone marrow aplasia with special focus on altered
      redox status and associated effects on hematopoietic microenvironment and
      epigenetic status of hematopoietic cells. The study involves the development of
      busulfan and cyclophosphamide mediated mouse model for aplastic anemia,
      characterization of the disease with blood and marrow analysis, cytochemical
      examinations of bone marrow, flowcytometric analysis of hematopoietic population
      and microenvironmental components, determination of ROS generation, apoptosis
      profiling, expressional studies of Notch-1 signaling cascade molecules,
      investigation of epigenetic modifications including global CpG methylation of
      DNA, phosphorylation of histone-3 with their effects on bone marrow kinetics and
      expressional analysis of the anti-oxidative molecules viz; SOD-2 and Sdf-1.
      Severe hematopoietic catastrophic condition was observed during aplastic anemia
      which involved peripheral blood pancytopenia, marrow hypocellularity and
      decreased hematopoietic stem/progenitor population. Generation of ROS was found
      to play a central role in the cellular devastation in aplastic marrow which on
      one hand can be correlated with the destruction of hematopoiesis supportive niche
      components and alteration of vital Notch-1 signaling and on other hand was found
      to be associated with the epigenetic chromatin modifications viz; global DNA CpG
      hypo-methylation, histone-3 phosphorylation promoting cellular apoptosis. Decline
      of anti-oxidant components viz; Sdf-1 and SOD-2 hinted towards the irreversible
      nature of the oxidative damage during marrow aplasia. Collectively, the findings
      hinted towards the mechanistic correlation among ROS generation,
      microenvironmental impairment and epigenetic alterations that led to
      hematopoietic catastrophe under aplastic stress. The findings may potentiate
      successful therapeutic strategy development for the dreadful condition concerned.

PMID- 29173809
TI  - The feasibility study of 177Lu production in Miniature Neutron Source Reactors
      using a multi-stage approach in Isfahan, Iran.
AB  - Miniature neutron source reactors (MNSRs) are among the safest and economic
      research reactors with potentials to be used for neutron studies. This manuscript
      explores the feasibility of 177Lu production in Isfahan MNSR reactor using direct
      production route. In this study, to assess the specific activity of the produced
      radioisotope, a simulation was carried out through the MCNPX2.6 code. The
      simulation was validated by irradiating a lutetium disc-like (99.98 chemical
      purity) at the thermal neutron flux of 5 * 1011 ncm2s-1 and an irradiation time
      of 4min. After the spectrometry of the irradiated sample, the experimental
      results of 177Lu production were compared with the simulation results. In
      addition, factor from the simulation was extracted by replacing it in the related
      equations in order to calculate specific activity through a multi-stage approach,
      and by using different irradiation techniques. The results showed that the
      simulation technique designed in this study is in agreement with the experimental
      approach (with a difference of approximately 3%). It was also found that the
      maximum 177Lu production at the maximum flux and irradiation time allows access
      to 723.5mCi/g after 27 cycles. Furthermore, the comparison of irradiation
      techniques showed that increasing the irradiation time is more effective in 177Lu
      production efficiency than increasing the number of irradiation cycles. In a way
      that increasing the irradiation time would postpone the saturation of the
      productions. On the other hand, it was shown that the choice of an appropriate
      irradiation technique for 177Lu production can be economically important in term
      of the effective fuel consumption in the reactor.

PMID- 29173810
TI  - Monte Carlo simulation of the full energy peak efficiency of an HPGe detector.
AB  - This paper presents a Monte Carlo method to obtain the full energy peak
      efficiency (FEPE) curve for a High Purity Germanium (HPGe) detector, as it is
      difficult and time-consuming to measure the FEPE curve experimentally. The Geant4
      simulation toolkit was adopted to establish a detector model since detector
      specifications provided by the nominal manufacturer are usually insufficient to
      calculate the accurate efficiency of a detector. Several detector parameters were
      optimized. FEPE curves for a given HPGe detectors over the energy range of 59.50
      1836keV were obtained and showed good agreements with those measured
      experimentally. FEPE dependences on detector parameters and source-detector
      distances were investigated. A best agreement with experimental result was
      achieved for a certain detector geometry and source-detector distance.

PMID- 29173811
TI  - Neutronic design study of accelerator driven system (ADS) for Jordan subcritical
      reactor as a neutron source for nuclear research.
AB  - In this paper, a preliminary neutronic design study of an accelerator driven
      subcritical system for Jordan Subcritical Assembly (JSA) is presented. The
      conceptual design of coupling the JSA core with proton accelerator and spallation
      target is investigated, and its feasibility as a neutron source for nuclear
      research, and possibly for target irradiation and isotope production evaluated.
      3D MCNPX model of the JSA reactor, the accelerator beam, and the Pb target was
      developed, based on actual reactor parameters. MCNPX calculations were carried
      out to estimate the absolute radial and axial neutron flux in the reactor, and to
      calculate the multiplication factor Keff and heat generated in the reactor.
      Numerical results showed an enormous increase in the neutron flux, by seven
      orders of magnitude, compared to the current JSA core design using Pu-Be source.
      In this research the results obtained are discussed and compared with those of
      the JSA, and do confirm the feasibility of utilizing the JSA as a viable nuclear
      research facility with adequate neutron flux.

PMID- 29173812
TI  - Activity measurement of 222Rn gas for a key comparison.
AB  - The Korea Research Institute of Standards and Science (KRISS) participated, in
      2015, in an international Key Comparison (KC) of gaseous radon-222 activity named
      CCRI (II) -K2.Rn-222 to confirm international equivalence of KRISS-established
      gaseous radon-222 measurement standards. LNHB acted as KC pilot laboratory. This
      paper describes the KC measurement procedure followed at KRISS using the defined
      solid angle counting method together with auxiliary relative measurement methods
      and presents the results.

PMID- 29173813
TI  - An approach to derive some simple empirical equations to calibrate nuclear and
      acoustic well logging tools.
AB  - A set of three pads was constructed from primary materials (sand, gravel and
      cement) to calibrate the gamma-gamma density tool. A simple equation was devised
      to convert the qualitative cps values to quantitative g/cc values. The neutron
      neutron porosity tool measures the qualitative cps porosity values. A direct
      equation was derived to calculate the porosity percentage from the cps porosity
      values. Cement-bond log illustrates the cement quantities, which surround well
      pipes. This log needs a difficult process due to the existence of various
      parameters, such as: drilling well diameter as well as internal diameter,
      thickness and type of well pipes. An equation was invented to calculate the
      cement percentage at standard conditions. This equation can be modified according
      to varying conditions.

PMID- 29173814
TI  - Absorbed doses in humans from 188Re-Rituximab in the free form and bound to
      superparamagnetic iron oxide nanoparticles: Biodistribution study in mice.
AB  - Absorbed doses to human organs from 188Re-Rituximab in the free form and bound to
      superparamagnetic iron oxide nanoparticles were predicted from results of the
      radiopharmaceutical biodistribution studies in mice by the RADAR method. Overall,
      equivalent and effective doses to human organs from the radiopharmaceutical on
      the nanoparticles were higher because of the enhanced permeability and retention
      effect. Liver, spleen and kidneys received higher equivalent doses than other
      organs (5.29, 3.70 and 3.06mSv/MBq, respectively, for the free
      radiopharmaceutical and 6.12, 3.96 and 3.93mSv/MBq for the drug on the
      nanoparticles).

PMID- 29173815
TI  - [Focusing on kidney transplantation in the elderly].
AB  - Due to the increase in life expectancy and the ageing of end-stage renal disease
      patients, the number of patients older than 65 years receiving a kidney
      transplant has been continuously growing over the last fifteen years. The
      benefits of renal transplantation compared to dialysis in terms of survival and
      quality of life have been shown in selected recipients over 65, or 70 years.
      However, the age remains the main limiting factor for the access to the waiting
      list, and the reluctance of the clinicians can be explained by the multiple
      comorbidities of these candidates, their limited life expectancy or the shortage
      of grafts. The challenge is to select the candidates who can benefit from renal
      transplantation, thanks to rigorous cardiovascular and neoplastic evaluation
      before enrolment and by taking into account the specific characteristics of
      elderly patients. The living donor appears to be the ideal option for elderly
      recipients, the alternative being the extended criteria donor, allowing waiting
      times to be limited. The choice of immunosuppressive therapy is also crucial in
      these patients at high risk of infectious and cardiovascular complications in
      whom the occurrence of acute rejection can have severe consequences. There are
      currently no specific recommendations for immunosuppression in elderly
      recipients, and we would need large-scale randomized studies to improve the
      prognosis of renal transplantation in this population.

PMID- 29173816
TI  - The Prediction of Body Composition in African Americans From Spine and Hip Dual
      Energy Absorptiometry.
AB  - Body composition, the makeup of the body's fat and lean tissue, is associated
      with important health outcomes and provides useful clinical information. Although
      body composition can be measured with total body dual-energy X-ray absorptiometry
      (DXA), this is rarely performed. As an alternative to total body DXA measurement,
      methods for estimation of body composition have been developed. These methods use
      soft tissue measures from spine and hip DXA to predict body composition and
      include prediction equations previously published by Leslie and proprietary
      equations within General Electric densitometry software. However, these estimates
      have not been tested in African Americans (AA), an ethnicity with a different
      distribution of fat than Caucasians (CA). Therefore, we examined the performance
      of the existing models in 99 CA and 162 AA subjects over the age of 40 who had
      total body, spine, and hip DXA measurements. We observed that existing models
      estimated body composition well in CA but underestimated fat mass and
      overestimated lean mass in AA. AA subjects were then randomly divided into 2
      equal-sized subgroups-the first to develop new prediction equations and the
      second to independently validate them. We found that body composition can be more
      accurately estimated using either a new model that we derived in AA subjects
      using backward stepwise elimination or by adding a fixed offset for AA to the
      previously published model. Our results demonstrate that body composition
      estimates from spine and hip DXA require consideration of race/ethnicity.

PMID- 29173817
TI  - Adaptive Bone Remodeling With New Design of the ABG Stem. Densitometric Study.
AB  - To establish the pattern of bone remodeling caused by a cementless, anatomic
      implant, we intend to evaluate the changes in bone mineral density observed after
      surgery in the Gruen zones. A controlled, prospective study was carried out, in
      which a group of 37 patients with primary coxarthrosis were densitrometrically
      analyzed over the 1 year period following the implant of an ANATO stem (Stryker).
      The patient's healthy hip was taken as the control. Any differences in the
      remodeling pattern were compared according to age, body mass index, and implant
      size. Decreases in bone mineral density were observed after 3 months in all of
      the zones studied. However, this bone mineral density loss was recovered in all
      zones by the end of the study, except in zone 7 where a decrease of 7.2% in bone
      mass was observed. In zones 2 and 6, where more loads are transmitted, bone mass
      preservation, in accordance with Wolff's law, can be seen. No differences were
      found in the remodeling pattern in relation to age and body mass index. There
      were also no differences related to stem size except in zones 1 and 7. The ANATO
      stem achieves an efficient transmission of loads between the stem and the
      proximal femur, providing enough mechanical loads for bone preservation. It is
      only in zone 7 where significant bone atrophy can be observed, attributable to
      the damage that this area suffers during the surgical process and the subsequent
      stress-shielding caused by the implant design.

PMID- 29173818
TI  - The enigma of stem cell-based therapies - how to conquer the death valley of
      therapy development.

PMID- 29173820
TI  - ORP-Mediated ER Contact with Endocytic Sites Facilitates Actin Polymerization.
AB  - Oxysterol binding protein-related proteins (ORPs) are conserved lipid binding
      polypeptides, enriched at ER contacts sites. ORPs promote non-vesicular lipid
      transport and work as lipid sensors in the context of many cellular tasks, but
      the determinants of their distinct localization and function are not understood.
      Here, we demonstrate that the yeast endocytic invaginations associate with the ER
      and that this association specifically requires the ORPs Osh2 and Osh3, which
      bridge the endocytic myosin-I Myo5 to the ER integral-membrane VAMP-associated
      protein (VAP) Scs2. Disruption of the ER contact with endocytic sites using ORP,
      VAP, myosin-I, or reticulon mutants delays and weakens actin polymerization and
      interferes with vesicle scission. Finally, we provide evidence suggesting that
      ORP-dependent sterol transfer facilitates actin polymerization at endocytic
      sites.

PMID- 29173819
TI  - Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface
      Invaginations.
AB  - Cell migration is essential for morphogenesis, organ formation, and homeostasis,
      with relevance for clinical conditions. The migration of primordial germ cells
      (PGCs) is a useful model for studying this process in the context of the
      developing embryo. Zebrafish PGC migration depends on the formation of cellular
      protrusions in form of blebs, a type of protrusion found in various cell types.
      Here we report on the mechanisms allowing the inflation of the membrane during
      bleb formation. We show that the rapid expansion of the protrusion depends on
      membrane invaginations that are localized preferentially at the cell front. The
      formation of these invaginations requires the function of Cdc42, and their
      unfolding allows bleb inflation and dynamic cell-shape changes performed by
      migrating cells. Inhibiting the formation and release of the invaginations
      strongly interfered with bleb formation, cell motility, and the ability of the
      cells to reach their target.

PMID- 29173821
TI  - Assessment of quality of life in patients surgically treated for penile cancer:
      Impact of aggressiveness in surgery.
AB  - PURPOSE: Health-related quality of life (HRQoL) evaluations are being
      increasingly used for clinical assessment of cancer treatment outcomes. For a
      patient, not only is life expectancy important, but also a general sense of
      sustained global health. Intuitively, the more disfiguring the treatment, the
      more pronounced could be the deterioration in the QoL. We aimed to compare
      various aspects of QoL in three groups of patients surgically treated for penile
      cancer by local excision, partial penectomy, or total penectomy. METHODS: HRQoL
      was assessed in 51 patients surgically treated for penile cancer. Total
      penectomy, partial penectomy, or wide local excision was performed in 11, 27, and
      13 patients, respectively. The EORTC QLQ-C30 questionnaire was used for HRQoL
      assessment. Relations between the patients and their partners were also assessed.
      RESULTS: Statistically significant negative correlation was found between
      aggressiveness of the surgical procedure and both, assessment of global health
      status (p = 0.04) and physical functioning (p = 0.047). The more aggressive the
      surgery, the lower was the patients' assessment of their QoL. Among the patients
      who maintained their partner relations postsurgery, 58.9% declared that their
      relations postoperatively were not inferior compared to those preoperatively.
      There was no statistically significant effect of the surgery type on relations
      with female partners (p = 0.619). CONCLUSION: The magnitude of disfigurement
      caused by surgical treatment of penile cancer had a significant impact on the
      selected QoL domains assessed by the EORTC QLQ C-30 questionnaire. There was no
      correlation between the scope of surgical intervention and partner relations.

PMID- 29173822
TI  - The effectiveness of a clinical and home-based physical activity program and
      simple lymphatic drainage in the prevention of breast cancer-related lymphedema:
      A prospective randomized controlled study.
AB  - PURPOSE: To investigate the effectiveness of a clinical and home-based, nurse-led
      physical activity program (PAP) and simple lymphatic drainage (SLD) in the
      prevention of breast cancer-related lymphedema. METHODS: A total of 52 breast
      cancer patients were randomized to either a PAP and SLD program (n = 25) or a
      control group (n = 27). Patients in both groups were also provided training for
      lymphedema. The PAP and SLD were administered through home visits by the
      investigators, twice a week for six weeks, in the intervention group. The control
      group did not undergo intervention. The circumference of the upper extremity,
      symptom severity, and physical function were measured in both groups. RESULTS:
      The upper extremity circumference increased by about two times from the baseline,
      in the control group, especially in the sixth week (p < 0.05). Lymphedema-related
      symptom severity scores were found to decrease significantly in the intervention
      group, compared to those at the baseline (p < 0.05). CONCLUSION: It was
      recommended that PAP and SLD, with a follow-up program, be used for patients who
      planned to undergo breast cancer surgery, starting from before surgery and
      continuing until after, to prevent breast cancer-related lymphedema.

PMID- 29173823
TI  - Barriers and facilitators of cervical cancer screening practices among African
      immigrant women living in Brisbane, Australia.
AB  - PURPOSE: To describe barriers and facilitators of cervical screening practices
      among African immigrant women living in Brisbane, Australia. METHOD: Nineteen
      African immigrant women (10 refugee and 9 non-refugee) were recruited using
      convenience sampling. The interviews were conducted with a semi-structured and
      open-ended questionnaire guide. All the interviews were audio recorded and
      transcribed verbatim. The data was manually analysed using interpretative
      thematic analysis. Thematic categories were identified and organised into
      coherent broader areas. RESULTS: Lack of knowledge about cervical cancer and Pap
      smear, the absence of warning signs, embarrassment, fear, concern about the
      gender of the service provider, lack of privacy, cultural and religious beliefs,
      and healthcare system factors were identified as barriers to screening. The
      results did not show any major differences between refugee and non-refugee women.
      Recommendation of the test by health professionals, provision of standardised
      information on the test, and preferences for female service providers were
      identified as facilitators of cervical screening. CONCLUSION: There is a need to
      provide culturally appropriate approaches to cervical screening practices and to
      enhance cultural competence among health professionals to apply service delivery
      models that honour group cultures.

PMID- 29173824
TI  - From vulnerability to passion in the end-of-life care: The lived experience of
      nurses.
AB  - PURPOSE: End-of-life (EOL) care is considered to be inherently difficult and
      vulnerable for patients and nurses. It also seems hard to develop passion for
      care during these problematic times. This study elucidates how EOL nurses
      interpret their care experience and how they transform their experience and
      mindset. METHODS: This study was conducted by organizing a reflective group based
      on the concept of group analysis for oncology and hospice nurses to share their
      experience. Thirteen registered nurses were enrolled from a medical center in
      northern Taiwan. Data drawn from the group dialogue was derived from six
      digitally recorded sessions and then analysed alone with the researcher's diaries
      and participants' feedback sheets. Interpretative Phenomenological Analysis (IPA)
      was used to analyze the data. RESULTS: The results showed that nurses who provide
      EOL care actually experience suffering by witnessing patients' suffering.
      However, the suffering authentically drives the nurses to encounter their own
      inner selves, to induce the shift of mindset, and then allow them to continuously
      provide and maintain the passion in EOL care. CONCLUSIONS: This study provides a
      new viewpoint for understanding of EOL nurses' experiences, indicating that this
      line of work may be recognized as a privilege. We recommend that the setting of a
      nurse reflective group is important and it may be considered in providing EOL
      care training for nurses. Hopefully the study results could shed lights for
      future policies regarding EOL care.

PMID- 29173825
TI  - Use of a symptom diary during chemotherapy: A mixed-methods evaluation of the
      patient perspective.
AB  - PURPOSE/OBJECTIVES: Patients' perceptions about tools for self-reporting symptoms
      experienced at home may influence both the patients' use of the tool and
      ultimately the efficacy of the interventions. The aim of this study was to
      determine the extent patients use a paper-pencil symptom-monitoring diary during
      chemotherapy treatment, to identify factors that mediate its use at home, and to
      determine perceptions patients have of the diary. METHODS: A quantitative survey
      assessed patients' use of the diary, their experiences and opinions. A secondary
      analysis of semi-structured interviews used was performed to determine how
      patients perceived being offered the diary for tracking symptoms and, if they did
      use it, their experiences with the diary. RESULTS: Eighty-seven patients (78%)
      used or had been using the diary during their chemotherapy treatment. Most
      patients felt that the diary supported them in discussing treatment-related
      symptoms with their doctors and nurses during hospital visits and helped them to
      deal with symptoms at home. However, diary users felt that their professional
      caregivers viewed the diary differently, specifically not valuing it enough to
      actively use it in their care. CONCLUSIONS: This study indicates that the
      majority of chemotherapy patients at our hospital perceive the symptom diary to
      be a feasible tool in terms of ease of use and time investment and that it is
      helpful. However, from the patient perspective, healthcare professionals'
      implementation of the diary in their behalf is lacking.

PMID- 29173826
TI  - Effect of an intervention based on basic Buddhist principles on the spiritual
      well-being of patients with terminal cancer.
AB  - PURPOSE: To evaluate the effect of an intervention based on basic Buddhist
      principles on the spiritual well-being of patients with terminal cancer. METHODS:
      This quasi-experimental research study had pre- and post-test control groups. The
      experimental group received conventional care and an intervention based on basic
      Buddhist principles for three consecutive days, including seven activities based
      on precept activities, concentration activities and wisdom activities. The
      control group received conventional care alone. RESULTS: Forty-eight patients
      participated in this study: 23 in the experimental group and 25 in the control
      group. Their mean age was 53 (standard deviation 10) years. The spiritual well
      being of participants in the experimental group was significantly higher than
      that of participants in the control group at the second post-test (P < 0.05).
      CONCLUSIONS: An intervention based on basic Buddhist principles improved the
      spiritual well-being of patients with terminal cancer. This result supports the
      beneficial effects of implementing this type of intervention for patients with
      terminal cancer.

PMID- 29173827
TI  - Hoping to reach a safe haven - Swedish families' lived experience when a family
      member is diagnosed with breast cancer.
AB  - PURPOSE: When a woman is diagnosed with breast cancer, it affects all family
      members. Therefore, the aim of this study was to elucidate family members lived
      experience when a family member is diagnosed with breast cancer. METHOD: The
      study had a hermeneutic phenomenological design including individual
      conversational interviews conducted face-to-face with six women with breast
      cancer and their family members at two different points of time, in order to
      elucidate families' lived experience, both as individuals and as a unit, from
      each family member's perspective. RESULTS: Living as a family in the presence of
      breast cancer is a challenging endeavour to regain an ordinary, safe life, hoping
      to reach a safe haven. The families felt that life as they knew it had
      disappeared and they were fumbling in the dark, trying to find support and
      guidance on their path to ordinary life. The family members were pursuing balance
      by attempting to keep the family together and maintaining a positive attitude
      while battling against fear and treatment-related side effects. Finally, the
      families were struggling with guilt and inadequacy, due to their difficulties in
      communicating the emotional distress that the illness brought upon them, at the
      same time as they felt abandoned by the healthcare professionals. CONCLUSIONS:
      Families experience an unmet need of information and support, which implies that
      healthcare professionals may want to acknowledge and include the family already
      at the time of diagnosis in order to help them endure and cope with the
      distressing experience and thus increase their wellbeing.

PMID- 29173828
TI  - Employing patient-reported outcome (PRO) measures to support newly diagnosed
      patients with melanoma: Feasibility and acceptability of a holistic needs
      assessment intervention.
AB  - PURPOSE: Living with a melanoma diagnosis can be challenging. We aimed to assess
      the feasibility, acceptability, and perceived value of a nurse-led intervention
      that utilised patient-reported outcome (PRO) measures to identify and address the
      supportive care needs of newly diagnosed patients with Stage I/II melanoma over
      the first 4 months post-diagnosis. METHODS: We conducted an exploratory, repeated
      measures, single-arm, feasibility trial. One baseline (4 weeks post-diagnosis;
      T1) and one follow-up intervention session (4 weeks after wide local excision;
      T3) took place, two months apart. Patient survey data were collected monthly, at
      four assessment points (T1-T4), followed by exit interviews. RESULTS: A
      recruitment rate of 55% (10/18) was achieved. The skin cancer nurse specialist
      (CNS) performed 19 in-clinic patient assessments within 6 months. One patient
      missed their follow-up intervention session (90% retention rate). Three
      participants (30%) were lost to follow-up at T4. Patients endorsed the
      standardised use of easy-to-use PRO measures as a means to help them shortlist,
      report and prioritise their needs. The CNS viewed the intervention as a highly
      structured activity that allowed tailoring support priority needs. A sizeable
      reduction in information needs was found from T1 to T4 (Standardised Response
      Mean [SRM] change = -0.99; p < 0.05). From T1 to T2, significant reductions in
      psychological (SRM change = -1.18; p < 0.001), practical (SRM change = -0.67; p <
      0.05) and sexuality needs (SRM change = -0.78; p < 0.05) were observed.
      CONCLUSIONS: The intervention appears to be feasible in clinical practice and
      acceptable to both patients with newly diagnosed melanoma and clinicians. Future
      research is warranted to test its effectiveness against standard care.

PMID- 29173829
TI  - Recruiting participants to a randomized controlled trial testing an intervention
      in palliative cancer care - The perspectives of health care professionals.
AB  - PURPOSE: The recruitment of participants to randomized controlled trials (RCTs)
      in palliative cancer care by health care professionals is often unsuccessful,
      which could result in failure to achieve study power. The purpose of this paper
      is to describe how health care professionals experienced recruiting patients and
      family caregivers to an RCT in palliative cancer care. METHODS: The study had a
      qualitative explorative design. Ten palliative home care settings were involved
      in the RCT and data were generated through focus group discussions and interviews
      with health care professionals who were responsible for the recruitment. The
      transcripts were analyzed with interpretive descriptive principles. RESULTS: The
      experiences of the health care professionals reveal that communicating the RCT
      design to patients and family caregivers was a challenging part of the
      recruitment but was considered a process of learning over time. The delicate
      situation that participants were living under added to the challenge and health
      care professionals believed that the randomized design was contrary to their
      normal approach to always offer the best possible support. CONCLUSIONS: The
      results contribute valuable knowledge for future trials in palliative cancer
      care. To promote successful recruitment, health care professionals may be in need
      of more training to improve their communication skills and it may be necessary to
      consider other research designs than the RCT.

PMID- 29173830
TI  - The lived experiences of patients with post-operative rectal cancer who suffer
      from altered bowel function: A phenomenological study.
AB  - PURPOSE: Altered bowel function is a common consequence of anal sphincter-saving
      surgery in rectal cancer patients, and bowel symptoms influence patients' daily
      life and psychosocial status. Patients have inadequate professional support
      because care specialists fail do fully appreciate the impact of the patients'
      symptoms. In-depth exploration of the individual's experience is essential to
      improve the quality of patient care. The purpose of this study was to explore the
      lived experiences of post-operative rectal cancer patients with altered bowel
      function. METHODS: This Husserlian descriptive phenomenological study recruited
      16 post-operative rectal cancer patients with altered bowel function. Data was
      collected through purposive sampling and one-on-one in-depth, semi-structured
      interviews. Narratives were analyzed thematically using Colaizzi's seven-step
      method. RESULTS: Three themes emerged, namely: "living in the restroom", "never
      backward", and "rebalancing on a new road". "Living in the restroom" described
      how patients frequent the restroom due to post-operative physical changes. "Never
      backward" outlined that such changes disturbed their mood, interrupted their
      daily activities, and affected their family life. "Rebalancing on a new road"
      described the patients' coping strategies, which included spiritual
      reconstruction, a new excrement model, an adjusted lifestyle, and peer support.
      CONCLUSIONS: Post-operative rectal cancer patients with altered bowel function
      frequent the restroom for prolonged periods, which disturbs their psychosocial
      status. However, they are forced to develop coping methods by themselves.
      Specialists can offer effective early post-operative interventions by thoroughly
      understanding each patient's symptomatic experience, symptom-related
      interferences, and primary concerns.

PMID- 29173831
TI  - An exploration of medical emergency team intervention at the end of life for
      people with advanced cancer.
AB  - PURPOSE: Recent advances in cancer therapies offer survival benefit when cure is
      no longer possible. The contribution of the Medical Emergency Teams (METs) in the
      context of advancing disease has received little empirical consideration. This
      study set out to explore MET intervention at the end of life for people with
      advanced cancer in an Australian comprehensive cancer centre, and its impact on
      quality of death. METHOD: A retrospective medical chart review was undertaken to
      explore MET response for people with advanced (incurable) cancer nearing end of
      life. Occurrence of MET interventions at the end of life and a quality of death
      score were recorded for two randomly selected cohorts of patients, those who
      experienced a MET response within their last week of life (n = 50) and those who
      did not (n = 50). RESULTS: The cohort who did not receive MET intervention had a
      significantly higher (better) quality of death score when compared with patients
      who did receive a MET intervention (p = 0.01). Within the cohort who received a
      MET intervention, a subgroup (n = 19) where the MET influenced end-of-life
      decision-making had a significantly higher quality of death score (p = 0.02) than
      patients in the MET cohort (n = 31) where the MET did not influence end-of-life
      care. CONCLUSION: The contribution of the MET to end-of-life care for patients
      with cancer has not previously been reported. Further research is now needed to
      prospectively examine MET involvement at the end of life with consideration to
      quality of patient care and death, family experience, and support requirements of
      MET members.

PMID- 29173832
TI  - The psychometric properties of the Turkish version of the Chemotherapy-Induced
      Peripheral Neuropathy Assessment Tool (CIPNAT).
AB  - PURPOSE: Chemotherapy-induced peripheral neuropathy is a common treatment-related
      adverse effect. It adversely affects the quality of life. Therefore, it is
      important to evaluate symptoms. The purpose of this study was to evaluate the
      validity and reliability of Chemotherapy-Induced Peripheral Neuropathy Assessment
      Tool in Turkish patients. METHODS: A convenience sample of 327 patients, being
      treated with peripheral neurotoxic chemotherapeutic agents were asked to fill in
      the questionnaire. The data was evaluated using SPSS 21 (SPSS Inc., Chicago IL,
      USA) statistical software. The verification of the structure obtained with CFA
      was provided by AMOS 21.0. Psychometric testing included internal consistency
      reliability (Cronbach's alpha coefficient and item-total correlations), test
      retest reliability, validity (exploratory factor analysis, confirmatory factor
      analysis and concurrent validity). RESULTS: The Cronbach alpha value of the scale
      was 0.97. The test-retest reliability results were significantly high. The CIPNAT
      significantly correlated with the European Organization for the Research and
      Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral
      Neuropathy. The model was validated by confirmatory factor analysis (chi2/sd =
      2.74, GFI = 0.95, AGFI = 0.92, CFI = 0.98, RMSEA = 0.07, and RMR = 0.009).
      CONCLUSIONS: The Turkish version of the CINAT was found to be reliable and valid
      with Turkish patients receiving chemotherapy. Use of the CIPNAT may lead to a
      better understanding of symptom. The CIPNAT can be used in future nursing
      research and practice as an assessment tool for peripheral neuropathy in patients
      with cancer who undergo chemotherapy.

PMID- 29173833
TI  - Effect of parental depression level on children's quality of life after
      haematopoietic stem cell transplantation.
AB  - PURPOSE: This descriptive cross-sectional study aimed to determine the impact of
      parental depression level on children's quality of life after haematopoietic stem
      cell transplantation (HSCT). METHOD: This study was conducted in a bone marrow
      transplantation unit of a children's hospital in Ankara, Turkey. The research
      sample consisted of 82 parents. Children aged 2-18 years and monitored in
      polyclinics 100 days after HSCT were included in the study. A sociodemographic
      data form, parent forms of the Pediatric Quality of Life Inventory, and the Beck
      Depression Inventory (BDI) were used. RESULTS: Forty (48%) mothers and 42 (51.2%)
      fathers participated in the study. Of the children, 30 (36.6%) were female and 52
      (63.4%) were male, and their mean age was 10.68 [standard deviation (SD) 4.80]
      years. Twenty-six children (31.7%) had been diagnosed with thalassaemia, and 29
      children (35.4%) had undergone HSCT in the previous 25-36 months. The mean total
      scale score on the Pediatric Quality of Life Inventory was 61.37 (SD 21.85), and
      the mean parental BDI Score was 14.57 (SD 11.03). Fourteen (17.1%) parents had
      severe depression and 10 (12.2%) parents had moderate depression. Low statistical
      correlation was found between the parental BDI score and the total scale score on
      the Pediatric Quality of Life (r = -0.281; P = 0.011). CONCLUSION: Parental
      depression level affects children's quality of life after HSCT. Following
      transplantation, it is important to evaluate parental depression level and
      provide support.

PMID- 29173834
TI  - Academy of Nutrition and Dietetics: Revised 2017 Scope of Practice for the
      Registered Dietitian Nutritionist.
AB  - The Academy of Nutrition and Dietetics (Academy) is the world's largest
      organization of food and nutrition professionals and the association that
      represents credentialed nutrition and dietetics practitioners-registered
      dietitian nutritionists (RDNs) and nutrition and dietetics technicians,
      registered (NDTRs). RDNs integrate research, professional development, and
      practice to stimulate innovation and discovery; collaborate to solve the greatest
      food and nutrition challenges now and in the future; focus on systemswide impact
      across the food, wellness, and health sectors; have a global impact in
      eliminating all forms of malnutrition; and amplify the contribution of nutrition
      and dietetics practitioners and expand workforce capacity and capability. The
      Revised 2017 Scope of Practice for the RDN reflects the position of the Academy
      on the essential role of the RDN in the direction and delivery of food and
      nutrition services. The scope of practice for the RDN is composed of education
      and credentialing, practice resources, Academy Standards of Practice and
      Professional Performance, codes of ethics, accreditation standards, state and
      federal regulations, national guidelines, and organizational policy and
      procedures. The Revised 2017 Scope of Practice for the RDN is used in conjunction
      with the Revised 2017 Standards of Practice (SOP) in Nutrition Care and the
      Standards of Professional Performance (SOPP) for RDNs. The SOP address activities
      related to direct patient and client care. The SOPP address behaviors related to
      the professional role of RDNs. These standards reflect the minimum competent
      level of nutrition and dietetics practice and professional performance for RDNs.
      A companion document addresses the scope of practice for the NDTR.

PMID- 29173835
TI  - Academy of Nutrition and Dietetics: Revised 2017 Standards of Practice in
      Nutrition Care and Standards of Professional Performance for Registered Dietitian
      Nutritionists.
AB  - Registered dietitian nutritionists (RDNs) face complex situations every day.
      Competently addressing the unique needs of each situation and applying standards
      appropriately are essential to providing safe, timely, patient-/client-/customer
      centered, quality nutrition and dietetics care and services. The Academy of
      Nutrition and Dietetics (Academy) leads the profession by developing standards
      that can be used by RDNs (who are credentialed by the Commission on Dietetic
      Registration) for self-evaluation to assess quality of practice and performance.
      The Standards of Practice reflect the Nutrition Care Process and workflow
      elements as a method to manage nutrition care activities with
      patients/clients/populations that include nutrition screening, nutrition
      assessment, nutrition diagnosis, nutrition intervention/plan of care, nutrition
      monitoring and evaluation, and discharge planning and transitions of care. The
      Standards of Professional Performance consist of six domains of professional
      performance: Quality in Practice, Competence and Accountability, Provision of
      Services, Application of Research, Communication and Application of Knowledge,
      and Utilization and Management of Resources. Within each standard, specific
      indicators provide measurable action statements that illustrate how the standard
      can be applied to practice. The Academy's Revised 2017 Standards of Practice and
      Standards of Professional Performance for RDNs, along with the Academy's Code of
      Ethics and the Revised 2017 Scope of Practice for the RDN, provide minimum
      standards and tools for demonstrating competence and safe practice and are used
      collectively to gauge and guide an RDN's performance in nutrition and dietetics
      practice.

PMID- 29173836
TI  - Alzheimer's disease combination treatment.

PMID- 29173837
TI  - Guest editorial: Mobile genetic elements and horizontal gene transfer in
      prokaryotes.

PMID- 29173838
TI  - Guest editorial: Microbiota: Microbiota and animal ecology, evolution and
      physiology: back to the future.

PMID- 29173839
TI  - Report of the 2017 meeting of the German Society for Protozoology.

PMID- 29173840
TI  - Report of the 2017 Protistology-UK Spring Meeting.

PMID- 29173843
TI  - International Items of Interest.

PMID- 29173841
TI  - Improving perceptions of empathy in patients undergoing low-yield computerized
      tomographic imaging in the emergency department.
AB  - OBJECTIVE: We assessed emergency department (ED) patient perceptions of how
      physicians can improve their language to determine patient preferences for 11
      phrases to enhance physician empathy toward the goal of reducing low-value
      advanced imaging. METHODS: Multi-center survey study of low-risk ED patients
      undergoing computerized tomography (CT) scanning. RESULTS: We enroled 305
      participants across nine sites. The statement "I have carefully considered what
      you told me about what brought you here today" was most frequently rated as
      important (88%). The statement "I have thought about the cost of your medical
      care to you today" was least frequently rated as important (59%). Participants
      preferred statements indicating physicians had considered their "vital signs and
      physical examination" (86%), "past medical history" (84%), and "what prior
      research tells me about your condition" (79%). Participants also valued
      statements conveying risks of testing, including potential kidney injury (78%)
      and radiation (77%). CONCLUSION: The majority of phrases were identified as
      important. Participants preferred statements conveying cognitive reassurance,
      medical knowledge and risks of testing. PRACTICE IMPLICATIONS: Our findings
      suggest specific phrases have the potential to enhance ED patient perceptions of
      physician empathy. Further research is needed to determine whether statements to
      convey empathy affect diagnostic testing rates.

PMID- 29173844
TI  - "Alternative facts" and orthodontic advertising in the United Kingdom.

PMID- 29173845
TI  - Tooth health should be considered when selecting which teeth to extract.

PMID- 29173846
TI  - Author's response.

PMID- 29173847
TI  - Malocclusion and health care.

PMID- 29173848
TI  - Oral health-related quality of life in surgery-first vs traditional orthognathic
      approach.

PMID- 29173850
TI  - Erratum.

PMID- 29173849
TI  - Authors' response.

PMID- 29173851
TI  - Erratum.

PMID- 29173853
TI  - Mixed messages.

PMID- 29173854
TI  - Alignment efficiency and esthetic performance of 4 coated nickel-titanium
      archwires in orthodontic patients over 8 weeks: A multicenter randomized clinical
      trial.
AB  - INTRODUCTION: The objective of this 4-arm parallel study was to evaluate the
      alignment efficiency and esthetic performance of 4 coated nickel-titanium
      archwires over an 8-week period. METHODS: Patients in the permanent dentition
      requiring maxillary and mandibular fixed orthodontic treatment with a preadjusted
      edgewise appliance were eligible for inclusion. Patients attending 4 hospital
      departments (United Kingdom and Italy) were randomly allocated to 1 of 4
      treatment interventions: (1) BioCosmetic (Forestadent, Pforzheim, Germany), 0.017
      in; (2) Titanol (Forestadent), 0.016 in; (3) TP Aesthetic (TP Orthodontics, La
      Porte, Ind), 0.014 in; and (4) Tooth Tone (Ortho Organizers, Calsbad, Calif)
      0.016 in. Block randomization with block sizes of 4 and 8 was used to ensure an
      allocation ratio of 1:1:1:1. The primary outcome was alignment efficiency
      determined by the reduction in Little's irregularity index (mm). Secondary
      outcomes were color change using the Commission Internationale de L'Eclairage
      L*a*b* system and percentage of coating loss. Blinding was only applicable to
      outcome assessment of alignment efficiency. Regression models with Sidak's
      multiple comparison of means were used to analyze the data. RESULTS: One hundred
      fifty patients (300 dental arches) were allocated to the treatment interventions,
      including 61 male and 89 female subjects with a mean age of 16.60 years. The
      average duration of follow-up was 63.65 days. Baseline characteristics for the
      archwire groups were similar. One patient was lost to follow-up. Five percent (n
      = 15) of the archwires fractured: BioCosmetic, 5.3% (n = 4); Titanol, 6.8% (n =
      5); TP Aesthetic, 5.3% (n = 4); and Tooth Tone, 2.7% (n = 2). We analyzed 283
      dental arches for alignment efficiency. There was no statistically significant
      difference for mean reduction in irregularity between the archwire groups (P =
      0.627): BioCosmetic (n = 71), 3.86 mm (95% CI, 3.31-4.41); Titanol (n = 69), 4.51
      mm (95% CI, 4.00-5.02); TP Aesthetic (n = 71), 4.13 mm (95% CI, 3.49-4.78); and
      Tooth Tone (n = 72), 4.21 mm (95% CI, 3.89-4.46). There was a statistically
      significant difference between archwire groups for color change (P = 0.001) and
      percentage of coating loss (P = 0.001), with BioCosmetic performing best in both
      parameters. CONCLUSIONS: There was no difference between the archwires for
      alignment efficiency. BioCosmetic performed statistically significantly better
      than did the other groups for both color change and coating loss. REGISTRATION:
      This trial was registered with the East Midlands NHS Research Ethics Committee
      (12/EM/0190). PROTOCOL: The protocol was not published before trial commencement.

PMID- 29173855
TI  - Short-term and long-term effectiveness of powered toothbrushes in promoting
      periodontal health during orthodontic treatment: A systematic review and meta
      analysis.
AB  - INTRODUCTION: Although powered toothbrushes have been reported to reduce
      gingivitis more than manual toothbrushes in the general population, the evidence
      regarding orthodontic patients has been inconclusive. Thus, we aimed to compare
      their effectiveness in relation to any available parameter regarding oral health
      in orthodontic patients with fixed appliances. METHODS: Searches without
      restrictions for published and unpublished literature and hand searching took
      place up to August 2017. Oral-health relevant data from randomized controlled
      trials of at least 4-weeks duration comparing powered and manual tooth brushing
      without supervision were reviewed. Data were classified as short term
      (assessments at 1-3 months) and long term (assessments at >3 months), and the
      random-effects method was used to combine treatment effects. Individual study
      risk of bias was assessed using the Cochrane Risk of Bias Tool, and the quality
      of evidence was evaluated according to the Grades of Recommendation, Assessment,
      Development and Evaluation approach. RESULTS: The initially identified articles
      were finally reduced to 9 randomized controlled trials investigating the
      periodontal health in 434 patients. Eight studies followed patients up to 3
      months, and 1 up to 12 months during treatment. One study was at low and the rest
      at unclear risk of bias. Overall, in the short term, there was low-quality
      evidence that powered toothbrushes provide a statistically significant benefit
      compared with manual brushing with regard to the gingival index (weighted mean
      difference, -0.079; 95% confidence interval, -0.146 to -0.012; P = 0.021) and
      indexes assessing gingival bleeding (standardized mean difference, -0.637; 95%
      confidence interval, -1.092 to -0.183; P = 0.006). In the long term, only 1
      available study showed a statistically significant benefit of powered over manual
      toothbrushes with regard to gingival index and bleeding. No differences were
      observed in probing pocket depth and relative attachment loss. For the rotation
      oscillation brushes that involved the greatest body of evidence, statistically
      significant reductions in gingival index and bleeding were demonstrated only in
      the long-term study. No included study provided quantified measurements regarding
      caries activity. CONCLUSIONS: Overall, powered toothbrushes may promote gingival
      health better than manual toothbrushes in orthodontic patients. However, no type
      demonstrated clear superiority. Better study standardization and reporting in
      longer follow-up studies are necessary to elucidate the clinical relevance of
      these results.

PMID- 29173856
TI  - Changes of bite force and occlusal contacts in the retention phase of orthodontic
      treatment: A controlled clinical trial.
AB  - INTRODUCTION: We aimed to determine whether appliance type affects changes in
      maximum voluntary bite force (MVBF) and the number of occlusal contacts (NOC)
      during retention, controlling for sex, age, and body mass index. METHODS: The
      sample comprised 176 examinees (70 male, 106 female) aged 14 to 20 years: 30 had
      maxillary and mandibular Essix retainers, 30 had wrap-around retainers, and 30
      had a combination of fixed mandibular canine-to-canine retainers bonded on each
      tooth separately (double twisted, 0.254 mm in diameter, stainless steel ligature
      wire) and Essix retainer in the maxillary arch; 86 with normal occlusion were not
      treated. MVBF and the NOC were measured immediately after removal of preadjusted
      edgewise appliances (Roth prescription), 6 weeks after that, and after the next 4
      weeks. RESULTS: Increases in MVBF and the NOC were demonstrated, but subjects
      with 2 Essix retainers showed lower values than did the others. Changes were
      related to type of appliance, sex, and age (P <0.05) but not to body mass index.
      The increase in NOC occurred faster than the increase of MVBF, more and sooner
      with the wrap-around retainer and in male subjects than with the Essix and in
      female subjects. MVBF and NOC nearly reached the values of the control subjects.
      CONCLUSIONS: Settling of the occlusion depends on appliance type: it takes longer
      in female patients and with Essix in both dental arches than with the other
      tested appliances.

PMID- 29173857
TI  - Effect of malocclusion on adults seeking orthodontic treatment.
AB  - INTRODUCTION: Our objective was to examine the Teen Oral Health-related Quality
      of Life (TOQOL) questionnaire for use in adults receiving orthodontic treatment
      and assess validity and reliability by age group. METHODS: Teenagers from 10 to
      18 years and adults 18 and over completed surveys at the orthodontic clinic at
      Boston University. The survey consisted of sociodemographic information, dental
      behavior questions, and the TOQOL instrument. Malocclusion severity was assessed
      using the Index of Orthodontic Treatment Need. RESULTS: Overall, 161 teens and
      146 adults participated. The mean ages were 13 years for the teens and 32 years
      for the adults. Subjects were represented by both sexes and diverse racial and
      ethnic backgrounds. In general, scores overall and by domains were higher for
      adults than for teens, signifying a greater effect of the malocclusion on the
      quality of life. Mean TOQOL scores as well as emotional and social domain scores
      (P <0.001) were worse (17.6) in adults than in teens (11.9; P <0.01). Construct
      validity was supported by strong a association of TOQOL scores with self-reported
      oral health. The Cronbach alpha was higher in adults overall and for all domains
      (0.75 in adults compared with 0.68 in teens). CONCLUSIONS: Adults who come for
      orthodontic treatment appear to be more affected by their malocclusion than are
      teens. The total TOQOL score and the emotional and social domains were
      significantly higher for adults. The total TOQOL score and the emotional and
      social domains were significantly higher (worse) for adults than teens. This
      project suggested that TOQOL may be a useful way to measure the impact of
      malocclusion on the quality of life in both adults and teens.

PMID- 29173858
TI  - Comparison of different midsagittal plane configurations for evaluating
      craniofacial asymmetry by expert preference.
AB  - INTRODUCTION: In this study, we aimed to compare 8 candidate midsagittal planes
      (MSPs) constructed from different median landmarks to determine the most
      appropriate one for evaluating craniofacial asymmetry. METHODS: We included 30
      patients (18 men, 12 women; mean age, 25.7 +/- 6.03 years) who visited the
      National Health Insurance Service Ilsan Hospital in Gyeonggi-do, Korea, with a
      complaint of facial asymmetry. Four MSPs passing through 2 median landmarks
      perpendicular to the Frankfort horizontal plane and 4 other MSPs passing through
      3 median landmarks were constructed. Menton, anterior nasal spine, and anterior
      nasal spine-to-posterior nasal spine line deviations were evaluated using these 8
      MSPs. Eight MSPs from 30 subjects were shown to 6 experts, who selected the
      planes that they considered the most appropriate. RESULTS: Experts most
      frequently selected the plane passing through nasion and basion perpendicular to
      the Frankfort horizontal plane (66 of 180 times; P <0.05). In evaluating
      craniofacial asymmetry, using MSPs passing through 3 median landmarks in the
      cranial base can lead to underestimation of the asymmetry of the menton, anterior
      nasal spine, and anterior nasal spine-to-posterior nasal spine line. CONCLUSIONS:
      We suggest using MSPs perpendicular to the Frankfort horizontal plane or a plane
      passing through anterior nasal spine in clinical practice.

PMID- 29173859
TI  - Relapse of anterior crowding 3 and 33 years postretention.
AB  - INTRODUCTION: The aim of this study was to evaluate the relapse of occlusal
      characteristics and maxillary and mandibular anterior crowding 3 and 33 years
      postretention. METHODS: The sample comprised 28 patients, 15 Class I and 13 Class
      II, treated with 4 premolar extractions, with a mean initial age of 12.72 years
      (SD, 0.99), a mean final age of 14.74 years (SD, 1.26), and a mean treatment time
      of 2.02 years (SD, 0.66). The mean short-term postretention age was 20.15 years
      (SD, 1.34), and the mean long-term postretention age was 49.40 years (SD, 4.54).
      The mean time of short-term postretention evaluation was 3.70 years (SD, 0.87)
      and the mean long-term postretention evaluation was 32.95 years (SD, 4.31). The
      maxillary and mandibular irregularity indexes were assessed on the initial,
      final, short-term, and long-term postretention stage dental casts. Peer
      Assessment Rating and the Little indexes were compared among the 4 stages by
      repeated measures analysis of variance and Tukey tests. RESULTS: Peer Assessment
      Rating index and maxillary anterior crowding were significantly improved with
      treatment, had significant relapses in the short term, and a slight and not
      statistically significant increase from short-term to long-term postretention
      evaluation. The mandibular irregularity index significantly decreased with
      treatment, and then significantly and progressively increased in the
      postretention stages. CONCLUSIONS: The occlusal characteristics and maxillary
      anterior crowding had significant relapses in the short term and remained stable
      from the short-term to the long-term postretention stages. Mandibular anterior
      crowding significantly decreased with treatment, showed a significant relapse in
      the short term, and continued to significantly increase in the long-term
      postretention stage.

PMID- 29173860
TI  - Differences in distances between maxillary posterior root apices and the sinus
      floor according to skeletal pattern.
AB  - INTRODUCTION: The aim of this study was to evaluate the distances from the
      maxillary posterior root apices to the inferior wall of the maxillary sinus using
      cone-beam computed tomography images and the relationships between roots and
      maxillary sinus according to age, sex, and skeletal pattern. METHODS: Three
      dimensional images of each root were checked, and the distances were measured
      along the true vertical axis from the apex of the root to the sinus floor in 118
      patients (63 male, 55 female) aged 10 to 28 years. Compare-means statistic tests
      were done to assess the differences between groups classified according to age,
      sex, and skeletal pattern. RESULTS: The frequency of root contact with the sinus
      floor increased from 70% at the second premolar to more than 80% at the buccal
      roots of the first and second molars. Male and older age (20-28 years) groups had
      significantly smaller distances or more protrusion of the root into the sinus
      than female and younger age (10-20 years) groups. The distances were shorter, or
      there was more protrusion of the root into the sinus in the hyperdivergent, down
      canted palatal plane, and large gonial angle groups. CONCLUSIONS: Male, older
      age, hyperdivergent skeletal pattern, and large gonial angle groups had
      significantly closer distances between maxillary root tips and the sinus floor or
      more protrusion of the roots into the sinus. The intrusion of the maxillary
      molars in those situations may be difficult and slow because of the pneumatized
      maxillary sinus.

PMID- 29173861
TI  - Possible alternative treatment for mandibular asymmetry by local unilateral IGF-1
      injection into the mandibular condylar cavity: Experimental study in mice.
AB  - INTRODUCTION: The purpose of this study was to investigate whether a local
      unilateral IGF-1 injection into the mandibular condylar cavity can induce
      unilateral endochondral mandibular growth without any systemic adverse effects.
      METHODS: Seventy-five 3-week-old male Jcl:ICR mice were used in this study. The
      mice were divided into 2 groups: control group (n = 22) and IGF-1 group (n = 53).
      In the IGF-1 group, human IGF-1 was injected into the right mandibular condylar
      cavity, and phosphate-buffered saline solution was injected into the left cavity,
      3 times per week for 10 weeks. RESULTS: There was no significant difference in
      body weight, serum human IGF-1 concentration, and soft tissue thickness of the
      cheeks including the masseter muscles between the 2 groups. Unilateral IGF-1
      injection induced a lateral shift of the mandible to the contralateral side, and
      microcomputed tomogtraphy analysis showed that unilateral IGF-1 injection induced
      endochondral growth in the condyle. Col2, Ihh, and Runx2 were extensively
      upregulated by the local unilateral IGF-1 injection in real-time reverse
      transcription polymerase chain reaction analysis. Proliferation marker KI67, IGF
      1 signaling molecule AKT1, and chondrogenic differentiation marker Col2 were
      strongly expressed in the IGF-1 injected condyle by immunohistochemistry. Vital
      labeling showed that the distance between the labels was increased in the IGF-1
      injection group compared with that of the control group. CONCLUSIONS: The results
      verified in this study indicated that local unilateral IGF-1 injection into the
      mandibular condylar cavity successfully induced unilateral endochondral
      mandibular growth in mice without any systemic adverse effects. Thus, local
      unilateral IGF-1 injection into the mandibular condylar cavity could be a useful
      alternative for mandibular asymmetry therapy during the growth period. However,
      additional experimental and clinical studies will be necessary to prove the real
      effect of this new therapy.

PMID- 29173862
TI  - Effects of vacuum-formed retainers on periodontal status and their retention
      efficiency.
AB  - INTRODUCTION: The stability of treatment results is a major concern in
      orthodontics. Numerous retention regimens to maintain stability have been
      introduced. The objectives of this study were to evaluate the effects of vacuum
      formed retainers (VFRs) on periodontal tissues and the retention efficiency of
      VFRs. METHODS: Forty patients were included in this study. Clinical effectiveness
      of VFRs for nighttime use only over a 12-month period was assessed by using the
      American Board of Orthodontics' Objective Grading System. Periodontal
      measurements and indexes were recorded and evaluated immediately after removal of
      the braces and after 1, 6, and 12 months of VFR use. RESULTS: There was no
      significant change in the total Objective Grading System score between the end of
      the active treatment period and the end of the 12-month retention period.
      However, regarding periodontal measurements, the plaque and gingival indexes
      decreased, whereas the bleeding on probing, probing depth, calculus index, and
      clinical attachment loss increased between the evaluated periods. CONCLUSIONS: In
      terms of periodontal health, the use of VFRs resulted in a slight periodontal
      attachment loss that seemed to be clinically insignificant, without gingival
      inflammation or recession. In terms of stability, VFRs were found to be effective
      in orthodontic retention.

PMID- 29173863
TI  - Two-dimensional vs 3-dimensional comparison of alveolar bone over maxillary
      incisors with A-point as a reference.
AB  - INTRODUCTION: Our objectives were to compare, relative to A-point, (1) bone
      thickness over the most forward maxillary incisor (MFMI) in 2 dimensions vs 3
      dimensions, and (2) bone thickness and inclination of each maxillary incisor in 3
      dimensions. METHODS: Thirty-four cone-beam computed tomography (CBCT) images were
      coded, and 2-dimensional (2D) cephalograms were derived from each image using
      Dolphin software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). A
      point and the MFMI crown were located. After reliability tests, alveolar bone
      buccal to 3 points on the MFMI root, bone to reference line Frankfort horizontal
      (FH)-A-point, and incisor inclination were measured. This procedure was repeated
      on the 3-dimensional (3D) CBCT images comparing MFMI with all maxillary incisors.
      The 2D and 3D measurements were compared using paired t tests, and 3D
      measurements were compared with analysis of variance. A 5% significance level was
      used for all tests. RESULTS: The MFMI's buccal bone thickness at the root apices
      and the distance between buccal bone and FH-A-point line at 2 root points were
      significantly greater in 2 dimensions than in 3 dimensions. In 3 dimensions, bone
      thickness at MFMI's root apex and the distance from FH-A-point line at all root
      points were significantly greater than those of the lateral incisors. Bone buccal
      to MFMI was significantly smaller than at the lateral incisors 3 mm from the
      cementoenamel junction. CONCLUSIONS: Evaluation of 2D CBCT derivations can result
      in overestimation of alveolar bone buccal to the maxillary incisor root apices
      compared with 3D evaluations. The anterior nasal spine obscures bone measurements
      over the maxillary incisors in 2 dimensions.

PMID- 29173864
TI  - Effect of temporomandibular joint articular disc repositioning on anterior open
      bite malocclusion: An orthodontic-surgical approach.
AB  - An anterior open bite is a challenge to orthodontic treatment; it has a
      multifactorial etiology and a wide range of intervention options.
      Temporomandibular joint (TMJ) disorders are a risk factor for the development of
      malocclusions such as the anterior open bite, especially in patients who have TMJ
      osteoarthritis with disc displacement. Articular disc repositioning surgery is an
      available option for treating this pathology, and it contributes to maintaining
      the condyles in a more stable position. The aim of this article was to report the
      case of a 20-year-old woman diagnosed with anterior open bite and TMJ
      osteoarthritis with bilateral disc displacement. The patient received both
      orthodontic treatment and TMJ disc repositioning surgery. Cone-beam computed
      tomography was used to create 3-dimensional models of the condyles with regional
      superposition, and assessment of bone remodeling was performed at different time
      intervals. Complete orthodontic and surgical treatment time was approximately 12
      months. The results provided a stable correction of the patient's anterior open
      bite with a 2-year follow-up and favorable bone remodeling of the condyles due to
      functional improvement of the TMJ.

PMID- 29173865
TI  - Application of palatal plate for nonextraction treatment in an adolescent boy
      with severe overjet.
AB  - A modified C-palatal plate (MCPP) is introduced as a treatment option for
      adolescent patients with Class I malocclusion and severe overjet. A boy, 10 years
      11 months old, was successfully treated without extractions in 22 months.
      Indications for clinical application of the MCPP as well as procedures and
      biomechanical analysis of the treatment effects are described in detail. The MCPP
      was used to distalize the maxillary dentition. The results were stable 1 year
      after retention. Clinicians should consider the application of MCPP as a
      nonextraction treatment option for adolescents with Class I malocclusion and
      severe overjet when the patient or parent refuses extractions.

PMID- 29173866
TI  - Computer-aided design and manufacture of hyrax devices: Can we really go digital?
AB  - The aim of this pilot study was to illustrate the feasibility of a new digital
      procedure to fabricate metallic orthodontic appliances. Hyrax appliances for
      rapid palatal expansion were produced for 3 patients using a CAD/CAM procedure
      without physical impressions or printed models. The work flow consisted of
      intraoral scanning, digital design with incorporation of a scanned prefabricated
      expansion screw, direct 3-dimensional metal printing via laser melting, welding
      of an expansion screw, insertion, and finally activation in the patients' mouths.
      Finite element analyses of the actual hyrax appliances were performed to ensure
      that the printable material used in combination with the chosen design would
      withstand the stress generated during activation. The results of these analyses
      were positive. The clinical results showed that this procedure is an efficient
      and viable digital way for constructing metallic orthodontic appliances. The
      flexibility of the digital appliance design, together with the biocompatibility
      and strength of the chosen material, offers a huge potential for more advanced
      appliance design.

PMID- 29173867
TI  - When things don't "ad" up.

PMID- 29173868
TI  - Compartmentalized Antimicrobial Defenses in Response to Flagellin.
AB  - Motility is often a pathogenicity determinant of bacteria targeting mucosal
      tissues. Flagella constitute the machinery that propels bacteria into appropriate
      niches. Besides motility, the structural component, flagellin, which forms the
      flagella, targets Toll-like receptor 5 (TLR5) to activate innate immunity. The
      compartmentalization of flagellin-mediated immunity and the contribution of
      epithelial cells and dendritic cells in detecting flagellin within luminal and
      basal sides are highlighted here, respectively. While a direct stimulation of the
      epithelium mainly results in recruitment of immune cells and production of
      antimicrobial molecules, TLR5 engagement on parenchymal dendritic cells can
      contribute to the stimulation of innate lymphocytes such as type 3 innate
      lymphoid cells, as well as T helper cells. This review, therefore, illustrates
      how the innate and adaptive immunity to flagellin are differentially regulated by
      the epithelium and the dendritic cells in response to pathogens that either
      colonize or invade mucosa.

PMID- 29173869
TI  - Human Gut Microbiome: Function Matters.
AB  - The human gut microbiome represents a complex ecosystem contributing essential
      functions to its host. Recent large-scale metagenomic studies have provided
      insights into its structure and functional potential. However, the functional
      repertoire which is actually contributed to human physiology remains largely
      unexplored. Here, by leveraging recent omics datasets, we challenge current
      assumptions regarding key attributes of the functional gut microbiome, in
      particular with respect to its variability. We further argue that the closing of
      existing gaps in functional knowledge should be addressed by a most-wanted gene
      list, the development and application of molecular and cellular high-throughput
      measurements, the development and sensible use of experimental models, as well as
      the direct study of observable molecular effects in the human host.

PMID- 29173870
TI  - A reappraisal of small- and large-fiber damage in carpal tunnel syndrome: New
      insights into the value of the EMLA test for improving diagnostic sensitivity.
AB  - OBJECTIVES: To reappraise the respective involvement of small- and large-fiber
      damage in carpal tunnel syndrome (CTS) and to determine the diagnostic
      sensitivity of autonomic tests compared to conventional nerve conduction study
      (NCS). METHODS: Thirty-two manual workers complaining of at least unilateral CTS
      were enrolled. They underwent clinical interview and completed the symptom
      severity scale of the Boston CTS Questionnaire (sssBCTQ) and the Neuropathic Pain
      Symptom Inventory (NPSI). In addition, transcarpal NCS was performed to
      investigate large sensory and motor fibers of the median nerve, while small
      autonomic fibers were assessed by recording sympathetic skin reflexes (SSR) at
      the palm and by grading skin wrinkling in response to eutectic mixture of local
      anesthetic (EMLA) cream application at the pulp of the index finger. For each
      neurophysiological variable, sensitivity and specificity values for the diagnosis
      of CTS were calculated and clinical correlations were studied. RESULTS: Among 64
      hands examined, 36 were clinically symptomatic, while 22 were clinically
      asymptomatic and served as controls. Among all the neurophysiological variables
      studied, only the values of transcarpal sensory nerve conduction velocity and the
      EMLA test grade were found to be more altered in clinically symptomatic hands,
      with also a trend towards prolonged distal motor latency. Overall, for the
      diagnosis of clinically symptomatic CTS, NCS, SSR, and the EMLA test had a
      sensitivity of 66.7%, 22.2%, and 69.4%, respectively, and a specificity of 72.7%,
      90.9%, and 50%, respectively. Combining NCS and the EMLA test led to a
      sensitivity of 88.9% and a specificity of 45.4%. The sssBCTQ (r=-0.34, P=0.009)
      and the total NPSI score (r=-0.41, P=0.001) correlated to a more altered EMLA
      test grade, but not to any NCS or SSR variables. In symptomatic hands, burning
      sensation was associated with more severe small-fiber lesion, while other pain
      and sensory symptoms were rather found to be reduced in case of large-fiber
      damage, evidenced by NCS alteration. CONCLUSIONS: This study confirms the
      discrepancy between conventional NCS results and clinical presentation of CTS,
      but still suggests a major involvement of Abeta fibers in the positive sensory
      symptoms of CTS, excepting burning sensation. On the other hand, the EMLA test
      was found to correlate with clinical data and to be able to improve sensitivity
      of neurophysiological investigation in diagnosing CTS.

PMID- 29173871
TI  - Erythema Multiforme Caused by Treatment With Topical Imiquimod 5% in a Patient
      With Gorlin Syndrome.

PMID- 29173872
TI  - Application of intraoperative transluminal core-biopsy for diagnosis of
      pancreatic head mass: A single center 15-year experience.
AB  - BACKGROUND: Pathology is the gold standard for diagnosis of pancreatic cancer.
      Preoperative endoscopic ultrasound-guided biopsy is an expensive procedure that
      is not routine in developing countries, hence a cheap, reliable alternative is
      required. AIM: To evaluate the effectiveness and safety of a new technique of
      intraoperative biopsy from pancreatic head mass. METHODS: Patients undergoing
      intraoperative transluminal core-biopsy (TLCB) for pancreatic head mass from
      January 2000 to June 2015 were included in this study. Following Kocher's
      maneuver, a biopsy was taken from the mass through the duodenum transluminally,
      using a commercial 16G automatic core-biopsy needle. Multiple tissue specimens
      were obtained for intraoperative frozen section examination. Depending on the
      pathological results, a decision was taken to either perform
      pancreaticoduodenectomy, duodenum-preserving pancreatic head resection, bypass
      surgery, or to just terminate the operation. The malignancy status of the lesion
      was confirmed by postoperative pathological examination and/or long-term follow
      up of the patients. RESULTS: A total of 525 patients were included.
      Intraoperative pathological reports revealed 436 malignant cases and 89 cases
      without evidence of malignancy. The sensitivity, specificity, false positive
      rate, and false negative rate were 97.7%, 100%, 0%, and 2.3%, respectively.
      Complications occurred in 2 patients. CONCLUSION: TLCB is a quick, safe,
      effective, and accurate method for intraoperative diagnosis method in patients
      with pancreatic head mass; it can provide reliable evidence for surgical decision
      making.

PMID- 29173873
TI  - Preoperative factors associated with technical difficulties of laparoscopic
      cholecystectomy in acute cholecystitis.
AB  - OBJECTIVE: To identify preoperative factors associated with surgical time and
      conversion of the laparoscopic cholecystectomy (LC) to open surgery in subjects
      with acute cholecystitis (AC). METHOD: We developed a cross-sectional study that
      included 99 subjects older than 17 years with definitive diagnosis of AC who had
      undergone to LC. Preoperative variables such as clinical data, laboratory markers
      and ultrasound findings as wall thickness, the size of the major calculus and the
      presence of: perivesicular fluid, multiple cholelithiasis, biliary mud or
      microlithiasis were registered. We consider indirect measures of technical
      difficulties of LC the total surgical time and the need for conversion to open
      surgery. We used the square chi and Mann-Whitney U test to stablish the
      correlation between preoperative variables and the technical difficulties of LC.
      We build ROC curves of the variables with significant statistical association (p
      <=0.05 and 95% confidence interval [95%CI]) to determine the cut-off points of
      better sensitivity and specificity to predict conversion of LC to open surgery.
      RESULTS: A gallbladder wall thickness >=6mm detected by ultrasound has a
      sensitivity of 87.5% and a specificity of 62.6% with OR 11.71 (95%CI: 1.38-99; p
      = 0.008) for predict conversion to open surgery. There was no relationship
      between surgical time and the preoperative evaluated variables. CONCLUSION: The
      gallbladder wall thickness detected by the ultrasound is associated with the need
      of conversion of LC to open surgery in subjects with AC, furthermore this finding
      could warn the surgeon on the complexity with a particular patient.

PMID- 29173874
TI  - Climate change: the role of the infectious disease community.

PMID- 29173875
TI  - Emergence of Plasmodium falciparum triple mutant in Cambodia.

PMID- 29173876
TI  - Can defective interfering RNAs affect the live attenuated influenza vaccine?

PMID- 29173877
TI  - Scabies and mortality.

PMID- 29173878
TI  - Can defective interfering RNAs affect the live attenuated influenza vaccine? -
      Authors' reply.

PMID- 29173879
TI  - Diagnostic algorithm for low-volume CSF samples in tuberculous meningitis.

PMID- 29173880
TI  - Prediction and prevention of tuberculosis in contacts.

PMID- 29173881
TI  - Prediction and prevention of tuberculosis in contacts.

PMID- 29173882
TI  - Prediction and prevention of tuberculosis in contacts - Authors' reply.

PMID- 29173883
TI  - Proton-pump inhibitors and glecaprevir plus pibrentasvir in HCV infection.

PMID- 29173885
TI  - Plague in Madagascar.

PMID- 29173884
TI  - Proton-pump inhibitors and glecaprevir plus pibrentasvir in HCV infection -
      Authors' reply.

PMID- 29173886
TI  - Marseilles' lazaretto for the 21st century.

PMID- 29173887
TI  - Highlights from IDWeek 2017.

PMID- 29173890
TI  - Tuberculosis of the tonsil simulating a cancer.

PMID- 29173891
TI  - A travelling camper with a spiking fever, headache, myalgia, hepatitis, and
      intracellular inclusions.

PMID- 29173892
TI  - Pilates workouts can reduce pain in pregnant women.
AB  - OBJECTIVE: This study aims to evaluate the effects of Pilates exercises for a
      decreasing pain in pregnant women. METHODS: A total of 40 pregnant women were
      divided into two groups, a control group (followed a standard pregnancy exercise
      regimen) and a Pilates group (completed a Pilates exercise regimen). A pain
      assessment was carried out after exercise, using a visual analog scale. The
      Pilates group workout program lasted 70-80 min per day, once a week, for 8 weeks.
      RESULTS: The reduction in the level of pain was found to be significantly greater
      in the group of pregnant women who completed the Pilates workout (p < 0.05).
      CONCLUSIONS: The results of this study indicated that Pilates is an effective,
      healthy, and feasible method of reducing pain in pregnancy, and is therefore a
      beneficial alternative workout for the suppression of pain in the third trimester
      of pregnancy.

PMID- 29173893
TI  - A novel in-hospital meal service improves protein and energy intake.
AB  - BACKGROUND & AIMS: Improvement of hospital meal services is a strategy to
      optimize protein and energy intake and prevent or treat malnutrition during
      hospitalization. FoodforCare (FfC) is a new concept comprising 6-protein-rich
      meals per day, provided directly at the bedside following proactive advice from a
      nutritional assistant. Our aim is to investigate whether this new concept, FfC,
      improves dietary intake and patient satisfaction, compared to the traditional 3
      meals a day service (TMS). METHODS: We performed a quasi experimental study at
      medical (Gastroenterology) and surgical (Gynecology, Urology, Orthopedics) wards.
      Patients were offered TMS (July 2015-May 2016; n = 326) or FfC meal service
      (after stepwise introduction per ward from January 2016-December 2016; n = 311).
      Primary outcome was the mean percentage of protein and energy intake relative to
      requirements, between patients receiving TMS and those receiving FfC, on the
      first and fourth day of full oral intake. Patient satisfaction comprised rating
      of the experienced quality of the meals and the meal service by means of a
      validated questionnaire. RESULTS: Patient characteristics were similar between
      groups, with the exception that the FfC group contained more oncology patients (p
      = 0.028). FfC improved mean daily protein intake (in g/day) relative to
      requirements (1.2 g/kg/day) at day 1 (mean % +/-SD: 79 +/- 33 vs. 59 +/- 28; p <
      0.05) and day 4 (73 +/- 38 vs. 59 +/- 29; p < 0.05). Mean daily energy intake (in
      kcal/day) relative to requirements improved at day 1 (88 +/- 34 vs. 70 +/- 30; p
      < 0.05) and day 4 (84 +/- 40 vs. 73 +/- 31; p = 0.05). On a scale of 1-10,
      patient satisfaction remained unchanged, in terms of food quality (7.7 +/- 1.5
      vs. 7.4 +/- 1.4; p = 0.09) and meal service (7.8 +/- 1.3 vs. 7.7 +/- 1.1; p =
      0.29). The FfC group was more satisfied with the appearance and smell of the
      meals (both p < 0.05). CONCLUSIONS: Implementation of this novel meal service
      substantially improved protein and energy intake while maintaining, and to some
      extent, improving patient satisfaction. REGISTRATION NO: NCT03195283.

PMID- 29173894
TI  - Generation of "Off-the-Shelf" Natural Killer Cells from Peripheral Blood Cell
      Derived Induced Pluripotent Stem Cells.
AB  - Current donor cell-dependent strategies can only produce limited "made-to-order"
      therapeutic natural killer (NK) cells for limited patients. To provide unlimited
      "off-the-shelf" NK cells that serve many recipients, we designed and demonstrated
      a holistic manufacturing scheme to mass-produce NK cells from induced pluripotent
      stem cells (iPSCs). Starting with a highly accessible human cell source,
      peripheral blood cells (PBCs), we derived a good manufacturing practice
      compatible iPSC source, PBC-derived iPSCs (PBC-iPSCs) for this purpose. Through
      our original protocol that excludes CD34+ cell enrichment and spin embryoid body
      formation, high-purity functional and expandable NK cells were generated from PBC
      iPSCs. Above all, most of these NK cells expressed no killer cell immunoglobulin
      like receptors (KIRs), which renders them unrestricted by recipients' human
      leukocyte antigen genotypes. Hence, we have established a practical "from blood
      cell to stem cells and back with less (less KIRs)" strategy to generate abundant
      "universal" NK cells from PBC-iPSCs for a wide range of patients.

PMID- 29173895
TI  - Mode of Surgical Injury Influences the Source of Urothelial Progenitors during
      Bladder Defect Repair.
AB  - The bladder urothelium functions as a urine-blood barrier and consists of basal,
      intermediate, and superficial cell populations. Reconstructive procedures such as
      augmentation cystoplasty and focal mucosal resection involve localized surgical
      damage to the bladder wall whereby focal segments of the urothelium and
      underlying submucosa are respectively removed or replaced and regeneration
      ensues. We demonstrate using lineage-tracing systems that urothelial regeneration
      following augmentation cystoplasty with acellular grafts exclusively depends on
      host keratin 5-expressing basal cells to repopulate all lineages of the de novo
      urothelium at implant sites. Conversely, repair of focal mucosal defects not only
      employs this mechanism, but in parallel host intermediate cell daughters
      expressing uroplakin 2 give rise to themselves and are also contributors to
      superficial cells in neotissues. These results highlight the diversity of
      urothelial regenerative responses to surgical injury and may lead to advancements
      in bladder tissue engineering approaches.

PMID- 29173896
TI  - The aPKC-CBP Pathway Regulates Post-stroke Neurovascular Remodeling and
      Functional Recovery.
AB  - Epigenetic modifications have emerged as attractive molecular substrates that
      integrate extrinsic changes into the determination of cell identity. Since stroke
      related brain damage releases micro-environmental cues, we examined the role of a
      signaling-induced epigenetic pathway, an atypical protein kinase C (aPKC)
      mediated phosphorylation of CREB-binding protein (CBP), in post-stroke
      neurovascular remodeling. Using a knockin mouse strain (CbpS436A) where the aPKC
      CBP pathway was defective, we show that disruption of the aPKC-CBP pathway in a
      murine focal ischemic stroke model increases the reprogramming efficiency of
      ischemia-activated pericytes (i-pericytes) to neural precursors. As a consequence
      of enhanced cellular reprogramming, CbpS436A mice show an increased transient
      population of locally derived neural precursors after stroke, while displaying a
      reduced number of i-pericytes, impaired vascular remodeling, and perturbed motor
      recovery during the chronic phase of stroke. Together, this study elucidates the
      role of the aPKC-CBP pathway in modulating neurovascular remodeling and
      functional recovery following focal ischemic stroke.

PMID- 29173897
TI  - A COUP-TFII Human Embryonic Stem Cell Reporter Line to Identify and Select Atrial
      Cardiomyocytes.
AB  - Reporter cell lines have already proven valuable in identifying, tracking, and
      purifying cardiac subtypes and progenitors during differentiation of human
      pluripotent stem cells (hPSCs). We previously showed that chick ovalbumin
      upstream promoter transcription factor II (COUP-TFII) is highly enriched in human
      atrial cardiomyocytes (CMs), but not ventricular. Here, we targeted mCherry to
      the COUP-TFII genomic locus in hPSCs expressing GFP from the NKX2.5 locus. This
      dual atrial NKX2.5EGFP/+-COUP-TFIImCherry/+ reporter line allowed identification
      and selection of GFP+ (G+)/mCherry+ (M+) CMs following cardiac differentiation.
      These cells exhibited transcriptional and functional properties of atrial CMs,
      whereas G+/M- CMs displayed ventricular characteristics. Via CRISPR/Cas9-mediated
      knockout, we demonstrated that COUP-TFII is not required for atrial specification
      in hPSCs. This new tool allowed selection of human atrial and ventricular CMs
      from mixed populations, of relevance for studying cardiac specification,
      developing human atrial disease models, and examining distinct effects of drugs
      on the atrium versus ventricle.

PMID- 29173898
TI  - Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor
      Cells.
AB  - Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell
      differentiation and function. Here, we induced differentiation of hPSCs (both
      embryonic and induced) to proepicardial/epicardial progenitor cells that cover
      the heart during development. Addition of retinoic acid (RA) and bone
      morphogenetic protein 4 (BMP4) promoted expression of the mesodermal marker
      PDGFRalpha, upregulated characteristic (pro)epicardial progenitor cell genes, and
      downregulated transcription of myocardial genes. We confirmed the (pro)epicardial
      like properties of these cells using in vitro co-culture assays and in ovo
      grafting of hPSC-epicardial cells into chick embryos. Our data show that RA +
      BMP4-treated hPSCs differentiate into (pro)epicardial-like cells displaying
      functional properties (adhesion and spreading over the myocardium) of their in
      vivo counterpart. The results extend evidence that hPSCs are an excellent model
      to study (pro)epicardial differentiation into cardiovascular cells in human
      development and evaluate their potential for cardiac regeneration.

PMID- 29173900
TI  - Movers and Stayers: Novel Assemblages in Changing Environments.
AB  - Increased attention to species movement in response to environmental change
      highlights the need to consider changes in species distributions and altered
      biological assemblages. Such changes are well known from paleoecological studies,
      but have accelerated with ongoing pervasive human influence. In addition to
      species that move, some species will stay put, leading to an array of novel
      interactions. Species show a variety of responses that can allow movement or
      persistence. Conservation and restoration actions have traditionally focused on
      maintaining or returning species in particular places, but increasingly also
      include interventions that facilitate movement. Approaches are required that
      incorporate the fluidity of biotic assemblages into the goals set and
      interventions deployed.

PMID- 29173899
TI  - Distinct Gene Expression and Epigenetic Signatures in Hepatocyte-like Cells
      Produced by Different Strategies from the Same Donor.
AB  - Hepatocyte-like cells (HLCs) can be generated through directed differentiation or
      transdifferentiation. Employing two strategies, we generated induced pluripotent
      stem cell (iPSC)-HLCs and hiHeps from the same donor cell line. Both types of
      HLCs clustered distinctly from each other during gene expression profiling. In
      particular, differences existed in gene expression for phase II drug metabolism
      and lipid accumulation, underpinned by H3K27 acetylation status in iPSC-HLCs and
      hiHeps. While distinct phenotypes were achieved in vitro, both types of HLCs
      demonstrated similar phenotypes following transplantation into Fah-deficient
      mice. In conclusion, functional HLCs can be obtained from the same donor using
      two strategies. Global gene expression defined the differences between those
      populations in vitro. Importantly, both HLCs displayed partial but markedly
      improved hepatic function following transplantation in vivo, demonstrating
      plasticity and the potential for cell-based modeling in the dish and cell-based
      therapy in the future.

PMID- 29173901
TI  - Clinical impact of dosimetric changes for volumetric modulated arc therapy in log
      file-based patient dose calculations.
AB  - PURPOSE: A log file-based method cannot detect dosimetric changes due to linac
      component miscalibration because log files are insensitive to miscalibration.
      Herein, clinical impacts of dosimetric changes on a log file-based method were
      determined. METHODS AND MATERIALS: Five head-and-neck and five prostate plans
      were applied. Miscalibration-simulated log files were generated by inducing a
      linac component miscalibration into the log file. Miscalibration magnitudes for
      leaf, gantry, and collimator at the general tolerance level were +/-0.5mm, +/-1
      degrees , and +/-1 degrees , respectively, and at a tighter tolerance level
      achievable on current linac were +/-0.3mm, +/-0.5 degrees , and +/-0.5 degrees ,
      respectively. Re-calculations were performed on patient anatomy using log file
      data. RESULTS: Changes in tumor control probability/normal tissue complication
      probability from treatment planning system dose to re-calculated dose at the
      general tolerance level was 1.8% on planning target volume (PTV) and 2.4% on
      organs at risk (OARs) in both plans. These changes at the tighter tolerance level
      were improved to 1.0% on PTV and to 1.5% on OARs, with a statistically
      significant difference. CONCLUSIONS: We determined the clinical impacts of
      dosimetric changes on a log file-based method using a general tolerance level and
      a tighter tolerance level for linac miscalibration and found that a tighter
      tolerance level significantly improved the accuracy of the log file-based method.

PMID- 29173902
TI  - Impact of deformable image registration accuracy on thoracic images with
      different regularization weight parameter settings.
AB  - PURPOSE: We assessed the deformable image registration (DIR) accuracy of thoracic
      images under different regularization weights using commercially available DIR
      software. METHODS: The thoracic 4-dimensional (4D) CT images of 10 patients were
      used. The datasets for these patients were provided by DIR-lab (www.dir-lab.com)
      and included a coordinate list of 300 anatomic landmarks that had been manually
      identified. The ANAtomically CONstrained Deformation Algorithm (ANACONDA) of
      RayStation (RaySearch Laboratories, Stockholm, Sweden) was used to deform the
      peak-inhale to peak-exhale images under different regularization weights (4, 40,
      400-default setting, 1500, 4000, 10,000, 15,000, 20,000, 30,000, and 40,000). The
      regularization weights were changed using a script. The registration error (RE)
      was determined by calculating the difference at each landmark point between the
      displacement calculated by the DIR software and that calculated by the landmark.
      We measured the computation time for each regularization weight setting. RESULTS:
      High regularization weights resulted in a smaller RE than that observed with
      lower regularization weights. The RE decreases rapidly with increase in
      regularization weight before reaching a plateau. No significant difference was
      found between a regularization weight of 400 and regularization weights of 4, 40,
      4000 or 40,000 (P value >0.05). The range of the average time was 8.4-12.2s.
      CONCLUSIONS: We concluded that the default setting for ANACONDA is stable with
      respect to regularization weight in the thoracic region.

PMID- 29173903
TI  - Radioluminescence from Tc-99m in glass predicts local dose.
AB  - The widely-used gamma-emitter Tc-99m has been shown to lead to optical emissions
      in mice and glass. We investigated the possibility that these emissions are due
      to the Cerenkov effect and whether the light emitted is proportional to local
      dose. By using a Geant4 Monte Carlo model matched to an experimental measurement,
      we show that the light detected by a small animal optical imaging system provides
      a 2D map of the dose throughout a glass sample. We conclude that
      radioluminescence from Tc-99m can be used to quantitatively measure dose in
      transparent materials, which could have applications in dosimetry and quality
      assurance.

PMID- 29173904
TI  - A novel method for assessment of fragmentation and beam-material interactions in
      helium ion radiotherapy with a miniaturized setup.
AB  - Radiotherapy with protons and carbon ions enables to deliver dose distributions
      of high conformation to the target. Treatment with helium ions has been suggested
      due to their physical and biological advantages. A reliable benchmarking of the
      employed physics models with experimental data is required for treatment
      planning. However, experimental data for helium interactions is limited, in part
      due to the complexity and large size of conventional experimental setups. We
      present a novel method for the investigation of helium interactions with matter
      using miniaturized instrumentation based on highly integrated pixel detectors.
      The versatile setup consisted of a monitoring detector in front of the PMMA
      phantom of varying thickness and a detector stack for investigation of outgoing
      particles. The ion type downstream from the phantom was determined by high
      resolution pattern recognition analysis of the single particle signals in the
      pixelated detectors. The fractions of helium and hydrogen ions behind the used
      targets were determined. As expected for the stable helium nucleus, only a minor
      decrease of the primary ion fluence along the target depth was found. E.g. the
      detected fraction of hydrogen ions on axis of a 220MeV/u 4He beam was below 6%
      behind 24.5cm of PMMA. Monte-Carlo simulations using Geant4 reproduce the
      experimental data on helium attenuation and yield of helium fragments
      qualitatively, but significant deviations were found for some combinations of
      target thickness and beam energy. The presented method is promising to contribute
      to the reduction of the uncertainty of treatment planning for helium ion
      radiotherapy.

PMID- 29173905
TI  - Optimization of imaging protocols for myocardial blood flow (MBF) quantification
      with 18F-flurpiridaz PET.
AB  - The new PET tracer, 18F-flurpiridaz, with high myocardial extraction allows
      quantitative myocardial blood flow (MBF) estimation from dynamic PET data and
      tracer kinetic modeling. The goal of this study is to determine the optimal
      imaging protocols and parameters using a realistic simulation study. The time
      activity curves (TACs) of different tissue organs from a 30-s infusion time (IT)
      of 18F-flurpiridaz in a dynamic PET study were extracted from a previous study.
      The TACs at different time points were incorporated in a series of realistic 3D
      XCAT phantoms from which the parameters of a 2-compartment model and the 'true'
      MBF of 18F-flurpiridaz were determined. The compartmental model was used to
      generate TACs from 7 additional ITs. PET projection data from the XCAT phantoms
      were generated using Monte Carlo simulation. They were reconstructed using an OS
      EM reconstruction algorithm with different update number (N) to obtain dynamic
      PET images. The blood and myocardial TACs were derived from the dynamic images
      from which the MBF and %MBF error was estimated. The %MBF error decreases with
      increasing N of the OS-EM and levels off after ~42. The 30-s IT gave the smallest
      %MBF error that decreases from ~0.57% to ~19.40%. The MBF for 2-min, 4-min, 8-min
      and 16-min IT were statistically significant different from the MBF for 30-s IT
      (P<0.05). Too fast or too slow infusion time gave higher %MBF error. The optimal
      imaging protocol in dynamic 18F-flurpiridaz PET for accurate quantitative MBF
      estimation was 30-s IT and N of ~42 for the OS-EM.

PMID- 29173906
TI  - Optimization of the exposure parameters in digital mammography using contrast
      detail metrics.
AB  - PURPOSE: Optimization studies in digital mammography aid to assure the image
      quality and radiological protection of the patient. The aim of this work is to
      test effectiveness and applicability of a method based on a Figure of Merit
      (FOM=(IQFinv)2/AGD) to improve all the exposure parameters (Target/Filter
      combination, kVp and mAs) in order to improve the image acquisition technique
      that will provide the best compromise between image quality and the average
      glandular dose (AGD). METHODS: A contrast-detail analysis, employing the test
      object CDMAM, was carried out for the digital mammography unit manufactured by
      Lorad Hologic - model Selenia. We simulated two breast thicknesses using phantoms
      and a Figure of Merit as optimization tool, which includes an indicator of image
      quality, the IQFinv and the average glandular dose. Images of the ACR and TORMAM
      phantoms were obtained with both, automatic and optimized exposure parameters. In
      order to compare the image quality, the SNR (Signal to Noise Ratio) was measured
      in each image. RESULTS: In the two phantoms, for both 4.5 and 7.5cm thicknesses,
      the AGDs obtained with the optimized parameters show a reduction. In addition,
      the images obtained with the optimized exposure parameters, had the same or a
      better image quality when compared to the images obtained using the automatic
      mode. CONCLUSIONS: The proposed optimization methodology proved to be an
      effective tool to improve the digital mammography unit, due to the use of
      objective metrics for evaluation and validation of the results.

PMID- 29173907
TI  - A software platform for statistical evaluation of patient respiratory patterns in
      radiation therapy.
AB  - AIM: The aim of this work was to design and evaluate a software tool for analysis
      of a patient's respiration, with the goal of optimizing the effectiveness of
      motion management techniques during radiotherapy imaging and treatment. MATERIALS
      AND METHODS: A software tool which analyses patient respiratory data files (.vxp
      files) created by the Varian Real-Time Position Management System (RPM) was
      developed to analyse patient respiratory data. The software, called RespAnalysis,
      was created in MATLAB and provides four modules, one each for determining
      respiration characteristics, providing breathing coaching (biofeedback training),
      comparing pre and post-training characteristics and performing a fraction-by
      fraction assessment. The modules analyse respiratory traces to determine signal
      characteristics and specifically use a Sample Entropy algorithm as the key means
      to quantify breathing irregularity. Simulated respiratory signals, as well as 91
      patient RPM traces were analysed with RespAnalysis to test the viability of using
      the Sample Entropy for predicting breathing regularity. RESULTS: Retrospective
      assessment of patient data demonstrated that the Sample Entropy metric was a
      predictor of periodic irregularity in respiration data, however, it was found to
      be insensitive to amplitude variation. Additional waveform statistics assessing
      the distribution of signal amplitudes over time coupled with Sample Entropy
      method were found to be useful in assessing breathing regularity. CONCLUSIONS:
      The RespAnalysis software tool presented in this work uses the Sample Entropy
      method to analyse patient respiratory data recorded for motion management
      purposes in radiation therapy. This is applicable during treatment simulation and
      during subsequent treatment fractions, providing a way to quantify breathing
      irregularity, as well as assess the need for breathing coaching. It was
      demonstrated that the Sample Entropy metric was correlated to the irregularity of
      the patient's respiratory motion in terms of periodicity, whilst other metrics,
      such as percentage deviation of inhale/exhale peak positions provided insight
      into respiratory amplitude regularity.

PMID- 29173908
TI  - Impact of pixel-based machine-learning techniques on automated frameworks for
      delineation of gross tumor volume regions for stereotactic body radiation
      therapy.
AB  - The aim of this study was to investigate the impact of pixel-based machine
      learning (ML) techniques, i.e., fuzzy-c-means clustering method (FCM), and the
      artificial neural network (ANN) and support vector machine (SVM), on an automated
      framework for delineation of gross tumor volume (GTV) regions of lung cancer for
      stereotactic body radiation therapy. The morphological and metabolic features for
      GTV regions, which were determined based on the knowledge of radiation
      oncologists, were fed on a pixel-by-pixel basis into the respective FCM, ANN, and
      SVM ML techniques. Then, the ML techniques were incorporated into the automated
      delineation framework of GTVs followed by an optimum contour selection (OCS)
      method, which we proposed in a previous study. The three-ML-based frameworks were
      evaluated for 16 lung cancer cases (six solid, four ground glass opacity (GGO),
      six part-solid GGO) with the datasets of planning computed tomography (CT) and
      18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images using
      the three-dimensional Dice similarity coefficient (DSC). DSC denotes the degree
      of region similarity between the GTVs contoured by radiation oncologists and
      those estimated using the automated framework. The FCM-based framework achieved
      the highest DSCs of 0.79+/-0.06, whereas DSCs of the ANN-based and SVM-based
      frameworks were 0.76+/-0.14 and 0.73+/-0.14, respectively. The FCM-based
      framework provided the highest segmentation accuracy and precision without a
      learning process (lowest calculation cost). Therefore, the FCM-based framework
      can be useful for delineation of tumor regions in practical treatment planning.

PMID- 29173909
TI  - Voxel-by-voxel correlation between radiologically radiation induced lung injury
      and dose after image-guided, intensity modulated radiotherapy for lung tumors.
AB  - PURPOSE: To correlate radiation dose to the risk of severe radiologically-evident
      radiation-induced lung injury (RRLI) using voxel-by-voxel analysis of the follow
      up computed tomography (CT) of patients treated for lung cancer with
      hypofractionated helical Tomotherapy. METHODS AND MATERIALS: The follow-up CT
      scans from 32 lung cancer patients treated with various regimens (5, 8, and 25
      fractions) were registered to pre-treatment CT using deformable image
      registration (DIR). The change in density was calculated for each voxel within
      the combined lungs minus the planning target volume (PTV). Parameters of a Probit
      formula were derived by fitting the occurrences of changes of density in voxels
      greater than 0.361gcm-3 to the radiation dose. The model's predictive capability
      was assessed using the area under receiver operating characteristic curve (AUC),
      the Kolmogorov-Smirnov test for goodness-of-fit, and the permutation test
      (Ptest). RESULTS: The best-fit parameters for prediction of RRLI 6months post RT
      were D50 of 73.0 (95% CI 59.2.4-85.3.7)Gy, and m of 0.41 (0.39-0.46) for
      hypofractionated (5 and 8 fractions) and D50 of 96.8 (76.9-123.9)Gy, and m of
      0.36 (0.34-0.39) for 25 fractions RT. According to the goodness-of-fit test the
      null hypothesis of modeled and observed occurrence of RRLI coming from the same
      distribution could not be rejected. The AUC was 0.581 (0.575-0.583) for
      fractionated and 0.579 (0.577-0.581) for hypofractionated patients. The
      predictive models had AUC>upper 95% band of the Ptest. CONCLUSIONS: The
      correlation of voxel-by-voxel density increase with dose can be used as a support
      tool for differential diagnosis of tumor from benign changes in the follow-up of
      lung IMRT patients.

PMID- 29173910
TI  - EPID-based in vivo dosimetry for stereotactic body radiotherapy of non-small cell
      lung tumors: Initial clinical experience.
AB  - PURPOSE: EPID-based in vivo dosimetry (IVD) has been implemented for stereotactic
      body radiotherapy treatments of non-small cell lung cancer to check both
      isocenter dose and the treatment reproducibility comparing EPID portal images.
      METHODS: 15 patients with lung tumors of small dimensions and treated with
      volumetric modulated arc therapy were enrolled for this initial experience. IVD
      tests supplied ratios R between in vivo reconstructed and planned isocenter
      doses. Moreover a gamma-like analysis between daily EPID portal images and a
      reference one, in terms of percentage of points with gamma-value smaller than 1,
      Pgamma<1, and mean gamma-values, gammamean, using a local 3%-3mm criteria, was
      adopted to check the treatment reproducibility. Tolerance levels of 5% for R
      ratio, Pgamma<1 higher than 90% and gammamean lower than 0.67 were adopted.
      RESULTS: A total of 160 EPID images, two images for each therapy session, were
      acquired during the treatment of the 15 patients. The overall mean of the R
      ratios was equal to 1.005+/-0.014 (1 SD), with 96.9% of tests within+/-5%. The 2D
      image gamma-like analysis showed an overall gammamean of 0.39+/-0.12 with 96.1%
      of tests within the tolerance level, and an average Pgamma<1 value equal to
      96.4+/-3.6% with 95.4% of tests with Pgamma<1>90%. Paradigmatic discrepancies
      were observed in three patients: a set-up error and a patient morphological
      change were identified thanks to CBCT image analysis whereas the third
      discrepancy was not fully justified. CONCLUSIONS: This procedure can provide
      improved patient safety as well as a first step to integrate IVD and CBCT dose
      recalculation.

PMID- 29173911
TI  - Medical image segmentation based on level set and isoperimetric constraint.
AB  - Level set based methods are being increasingly used in image segmentation. In
      these methods, various shape constraints can be incorporated into the energy
      functionals to obtain the desired shapes of the contours represented by their
      zero level sets of functions. Motivated by the isoperimetric inequality in
      differential geometry, we propose a segmentation method in which the
      isoperimetric constrain is integrated into a level set framework to penalize the
      ratio of its squared perimeter to its enclosed area of an active contour. The new
      model can ensure the compactness of segmenting objects and complete missing
      or/and blurred parts of their boundaries simultaneously. The isoperimetric shape
      constraint is free of explicit expressions of shapes and scale-invariant. As a
      result, the proposed method can handle various objects with different scales and
      does not need to estimate parameters of shapes. Our method can segment lesions
      with blurred or/and partially missing boundaries in ultrasound, Computed
      Tomography (CT) and Magnetic Resonance (MR) images efficiently. Quantitative
      evaluation also confirms that the proposed method can provide more accurate
      segmentation than two well-known level set methods. Therefore, our proposed
      method shows potential of accurate segmentation of lesions for applying in
      diagnoses and surgical planning.

PMID- 29173912
TI  - Generation of synthetic CT using multi-scale and dual-contrast patches for brain
      MRI-only external beam radiotherapy.
AB  - PURPOSE: To create a synthetic CT (sCT) from conventional brain MRI using a patch
      based method for MRI-only radiotherapy planning and verification. METHODS:
      Conventional T1 and T2-weighted MRI and CT datasets from 13 patients who
      underwent brain radiotherapy were included in a retrospective study whereas 6
      patients were tested prospectively. A new contribution to the Non-local Means
      Patch-Based Method (NMPBM) framework was done with the use of novel multi-scale
      and dual-contrast patches. Furthermore, the training dataset was improved by pre
      selecting the closest database patients to the target patient for computation
      time/accuracy balance. sCT and derived DRRs were assessed visually and
      quantitatively. VMAT planning was performed on CT and sCT for hypothetical PTVs
      in homogeneous and heterogeneous regions. Dosimetric analysis was done by
      comparing Dose Volume Histogram (DVH) parameters of PTVs and organs at risk
      (OARs). Positional accuracy of MRI-only image-guided radiation therapy based on
      CBCT or kV images was evaluated. RESULTS: The retrospective (respectively
      prospective) evaluation of the proposed Multi-scale and Dual-contrast Patch-Based
      Method (MDPBM) gave a mean absolute error MAE=99.69+/-11.07HU (98.95+/-8.35HU),
      and a Dice in bones DIbone=83+/-0.03 (0.82+/-0.03). Good agreement with
      conventional planning techniques was obtained; the highest percentage of DVH
      metric deviations was 0.43% (0.53%) for PTVs and 0.59% (0.75%) for OARs. The
      accuracy of sCT/CBCT or DRRsCT/kV images registration parameters was <2mm and <2
      degrees . Improvements with MDPBM, compared to NMPBM, were significant.
      CONCLUSION: We presented a novel method for sCT generation from T1 and T2
      weighted MRI potentially suitable for MRI-only external beam radiotherapy in
      brain sites.

PMID- 29173913
TI  - Temporally separating Cherenkov radiation in a scintillator probe exposed to a
      pulsed X-ray beam.
AB  - Cherenkov radiation is generated in optical systems exposed to ionising
      radiation. In water or plastic devices, if the incident radiation has components
      with high enough energy (for example, electrons or positrons with energy greater
      than 175keV), Cherenkov radiation will be generated. A scintillator dosimeter
      that collects optical light, guided by optical fibre, will have Cherenkov
      radiation generated throughout the length of fibre exposed to the radiation field
      and compromise the signal. We present a novel algorithm to separate Cherenkov
      radiation signal that requires only a single probe, provided the radiation source
      is pulsed, such as a linear accelerator in external beam radiation therapy. We
      use a slow scintillator (BC-444) that, in a constant beam of radiation, reaches
      peak light output after 1 microsecond, while the Cherenkov signal is detected
      nearly instantly. This allows our algorithm to separate the scintillator signal
      from the Cherenkov signal. The relative beam profile and depth dose of a linear
      accelerator 6MV X-ray field were reconstructed using the algorithm. The
      optimisation method improved the fit to the ionisation chamber data and improved
      the reliability of the measurements. The algorithm was able to remove 74% of the
      Cherenkov light, at the expense of only 1.5% scintillation light. Further
      characterisation of the Cherenkov radiation signal has the potential to improve
      the results and allow this method to be used as a simpler optical fibre dosimeter
      for quality assurance in external beam therapy.

PMID- 29173914
TI  - Conversion factors of effective and equivalent organ doses with the air kerma
      area product in patients undergoing coronary angiography and percutaneous
      coronary interventions.
AB  - To derive effective dose (E), organ dose (HT) and conversion factors with the air
      kerma area product (KAP) in coronary angiography (CA) and percutaneous coronary
      intervention (PCI) by the radial route, using the ICRP 103 tissue weighting
      factors. The study included 34 patients referred for CA and 31 for PCI. E and HT
      were derived from in-the-field KAP measurements using Montecarlo methods. Median
      KAP of 23.2 and 56.8Gycm2 and E of 6.9 and 20.0mSv were found for CA and PCI,
      respectively. Mean KAP and E were significantly higher in males than in females
      (52.4+/-40.0 vs 32.3+/-16.6Gycm2; p=0.02) and (16.8+/-13.6 vs 10.7+/-5.8mSv;
      p=0.04). KAP (r=0.39; p=0.001) and E (r=0.34; p=0.005) showed a significant
      correlation with the patient's weight. Conversion factors between KAP and E
      (E/KAP) were 0.30+/-0.04mSvGy-1cm-2 for CA and 0.33+/-0.05mSvGy-1cm-2 for PCI. No
      significant differences in the E/KAP between males and females were found (0.31+/
      0.05 vs 0.33+/-0.05; p=0.08). Again, no significant correlation was found between
      E/KAP and patient's weight (r=0.23; p=0.07). The correlation between E and KAP
      was excellent for CA (r=0.99) and PCI (r=0.96). The correlation between HT and
      KAP ranged from r=0.87 to r=1 and from r=0.71 to r=0.98 for CA and PCI,
      respectively. A single factor, the total KAP, could be used for a specific
      acquisition protocol to reliably estimate E and HT without the need of a
      patient's specific analysis. Conversion factors might be installation, X-ray beam
      quality or protocol dependent.

PMID- 29173915
TI  - Optimization of a large-area detector-block based on SiPM and pixelated LYSO
      crystal arrays.
AB  - We present the performance evaluation of a large-area detector module based on
      the ArrayC-60035-64P, an 8*8 array of tileable, 7.2mm pitch, silicon
      photomultipliers (SiPM) by SensL, covering a total area of 57.4mm*57.4mm. We
      characterized the ArrayC-60035-64P, operating at room temperature, using LYSO
      pixelated crystal arrays of different pitch sizes (1.075, 1.430, 1.683, 2.080 and
      2.280mm) to determine the resolvable crystal size. After an optimization process,
      a 7mm thick coupling light guide was used for all crystal pitches. To identify
      the interaction position a 16-channel (8 columns, 8 rows) symmetric charge
      division (SCD) readout board together with a center-of-gravity algorithm was
      used. Based on this, we assembled the detector modules using a 40*40 LYSO, 1.43mm
      pitch array, covering the total detector area. Calibration was performed using a
      137Cs source resulting in excellent crystal maps with minor geometric distortion,
      a mean 4.1 peak-to-valley ratio and 9.6% mean energy resolution for 662keV
      photons in the central region. The resolvability index was calculated in the x
      and y directions with values under 0.42 in all cases. We show that these large
      area SiPM arrays, combined with a 16-channel SCD readout board, can offer high
      spatial resolution, without processing a big number of signals, attaining
      excellent energy resolution and detector uniformity.

PMID- 29173916
TI  - Dosimetric effect of uncorrected rotations in lung SBRT with stereotactic imaging
      guidance.
AB  - PURPOSE: To evaluate the dosimetric impact of uncorrected rotations on the
      planning target volume (PTV) coverage for early stage non-small cell lung cancer
      patients treated with stereotactic body radiotherapy using Brainlab ExacTrac
      image guidance. METHODS: Twenty-two patients were retrospectively selected. Two
      scenarios of uncorrected rotations were simulated with magnitude of 1 degrees , 2
      degrees , 3 degrees  and 5 degrees : (1) rotation around the treatment isocenter;
      and (2) roll and yaw rotations around a setup isocenter. The D95 of PTV from
      recalculated dose on the rotated CT was compared to that from the clinical plan.
      A logistic regression model was used to predict the probability of dose
      differences between recalculated and original plans that are less than 2% based
      on the rotation angle, PTV volume, and distance between the treatment and setup
      isocenter. RESULTS: Logistic regression model showed the uncorrected isocentric
      rotations of up to 2.5 degrees  in all directions have negligible dosimetric
      impact. For non-isocentric rotations, a rotational error of 2 degrees  may cause
      significant under-dose of the PTV. Statistically significant (p<0.05) parameters
      in the logistic regression model were angle for isocentric rotations, angle and
      distance for non-isocentric roll rotations, and angle, distance and the PTV
      volume for non-isocentric yaw rotations. CONCLUSIONS: The severity of the dose
      deviations due to uncorrected rotations depends on the type and magnitude of the
      rotation, the volume of the PTV, and the distance between the treatment and setup
      isocenter, which should be taken into consideration when making clinical judgment
      of whether the rotational error could be ignored.

PMID- 29173917
TI  - Comparison between new-generation SiPM-based and conventional PMT-based TOF
      PET/CT.
AB  - PURPOSE: This study aimed to determine whether the SiPM-PET/CT, Discovery MI
      (DMI) performs better than the PMT-PET/CT system, Discovery 710 (D710). METHODS:
      The physical performance of both systems was evaluated using NEMA NU 2 standards.
      Contrast (%), uniformity and image noise (%) are criteria proposed by the
      Japanese Society of Nuclear Medicine (JSNM) for phantom tests and were determined
      in images acquired from Hoffman and uniform phantoms using the DMI and D710.
      Brain and whole-body [18F]FDG images were also acquired from a healthy male using
      the DMI and D710. RESULTS: The spatial resolution at 1.0cm off-center in the DMI
      and D710 was 3.91 and 4.52mm, respectively. The sensitivity of the DMI and D710
      was 12.62 and 7.50cps/kBq, respectively. The observed peak noise-equivalent count
      rates were 185.6kcps at 22.5kBq/mL and 137.0kcps at 29.0kBq/mL, and the scatter
      fractions were 42.1% and 37.9% in the DMI and D710, respectively. The D710 had
      better contrast recovery and lower background variability. Contrast, uniformity
      and image noise in the DMI were 61.0%, 0.0225, and 7.85%, respectively. These
      outcomes were better than those derived from the D710 and satisfied the JSNM
      criteria. Brain images acquired by the DMI had better grey-to-white matter
      contrast and lower image noise at the edge of axial field of view. CONCLUSIONS:
      The DMI offers better sensitivity, performance under conditions of high count
      rates and image quality than the conventional PMT-PET/CT system, D710.

PMID- 29173918
TI  - Evaluation of digital tomosynthesis reconstruction algorithms used to reduce
      metal artifacts for arthroplasty: A phantom study.
AB  - To investigate methods to reduce metal artifacts during digital tomosynthesis for
      arthroplasty, we evaluated five algorithms with and without metal artifact
      reduction (MAR)-processing tested under different radiation doses (0.54, 0.47,
      and 0.33mSv): adaptive steepest descent projection onto convex sets (ASD-POCS),
      simultaneous algebraic reconstruction technique total variation (SART-TV),
      filtered back projection (FBP), maximum likelihood expectation maximization
      (MLEM), and SART. The algorithms were assessed by determining the artifact index
      (AI) and artifact spread function (ASF) on a prosthesis phantom. The AI data were
      statistically analyzed by two-way analysis of variance. Without MAR-processing,
      the greatest degree of effectiveness of the MLEM algorithm for reducing
      prosthetic phantom-related metal artifacts was achieved by quantification using
      the AI (MLEM vs. ASD-POCS, SART-TV, SART, and FBP; all P<0.05). With MAR
      processing, the greatest degree of effectiveness of the MLEM, ASD-POCS, SART-TV,
      and SART algorithms for reducing prosthetic phantom-related metal artifacts was
      achieved by quantification using the AI (MLEM, ASD-POCS, SART-TV, and SART vs.
      FBP; all P<0.05). When assessed by ASF, metal artifact reduction was largest for
      the MLEM algorithm without MAR-processing and ASD-POCS, SART-TV, and SART
      algorithm with MAR-processing. In ASF, the effect of metal artifact reduction was
      always greater at reduced radiation doses, regardless of which reconstruction
      algorithm with and without MAR-processing was used. In this phantom study, the
      MLEM algorithm without MAR-processing and ASD-POCS, SART-TV, and SART algorithm
      with MAR-processing gave improved metal artifact reduction.

PMID- 29173919
TI  - Dosimetric evaluation near lung and soft tissue interface region during
      respiratory-gated and non-gated radiotherapy: A moving phantom study.
AB  - Challenges in treating lung tumours are related to the respiratory-induced tumour
      motion and the accuracy of dose calculation in charged particle disequilibrium
      condition. The dosimetric characteristics near the interface of lung and Perspex
      media in a moving phantom during respiratory-gated and non-gated radiotherapy
      were investigated using Gafchromic EBT2 and the MOSkin detector. The MOSkin
      detectors showed good agreement with the EBT2 films during static and gated
      radiotherapy. In static radiotherapy, the penumbral widths were found to be
      3.66mm and 7.22mm in Perspex and lung media, respectively. In non-gated (moving)
      radiotherapy with 40mm respiratory amplitude, dose smearing effect was observed
      and the penumbral widths were increased to 28.81mm and 26.40mm, respectively.
      This has been reduced to 6.85mm and 9.81mm, respectively, in gated radiotherapy
      with 25% gating window. There were still some dose discrepancies as compared to
      static radiotherapy due to the residual motion. This should be taken into account
      in the margin generation for the target tumour.

PMID- 29173920
TI  - Evaluation and clinical implementation of in vivo dosimetry for kV radiotherapy
      using radiochromic film and micro-silica bead thermoluminescent detectors.
AB  - PURPOSE: kV radiotherapy treatment calculations are based on flat, homogenous,
      full-scatter reference conditions. However, clinical treatments often include
      surface irregularities and inhomogeneities, causing uncertainty. Therefore,
      confirmation of actual delivered doses in vivo is valuable. The current study
      evaluates, and implements, radiochromic film and micro silica bead TLD for in
      vivo kV dosimetry. METHODS: The kV energy and dose response of EBT3 film and
      silica bead TLD was established and uncertainty budgets determined. In vivo
      dosimetry measurements were made for a consecutive series of 30 patients using
      the two dosimetry systems. RESULTS: Energy dependent calibration factors were
      required for both dosimetry systems. The standard uncertainty estimate for in
      vivo measurement with film was 1.7% and for beads was 1.5%. The mean measured
      dose was -2.1% for film and -2.6% for beads compared to prescription. Deviations
      up to -9% were found in cases of large surface irregularity, or with underlying
      air cavities or bone. Dose shielding by beads could be clinically relevant at low
      kV energies and superficial depths. CONCLUSIONS: Both film and beads may be used
      to provide in vivo verification of delivered doses in kV radiotherapy,
      particularly for complex situations that are not well represented by standard
      reference condition calculations.

PMID- 29173921
TI  - Multi-institutional comparison of simulated treatment delivery errors in ssIMRT,
      manually planned VMAT and autoplan-VMAT plans for nasopharyngeal radiotherapy.
AB  - PURPOSE: To quantify the impact of simulated errors for nasopharynx radiotherapy
      across multiple institutions and planning techniques (auto-plan generated
      Volumetric Modulated Arc Therapy (ap-VMAT), manually planned VMAT (mp-VMAT) and
      manually planned step and shoot Intensity Modulated Radiation Therapy (mp
      ssIMRT)). METHODS: Ten patients were retrospectively planned with VMAT according
      to three institution's protocols. Within one institution two further treatment
      plans were generated using differing treatment planning techniques. This resulted
      in mp-ssIMRT, mp-VMAT, and ap-VMAT plans. Introduced treatment errors included
      Multi Leaf Collimator (MLC) shifts, MLC field size (MLCfs), gantry and collimator
      errors. A change of more than 5% in most selected dose metrics was considered to
      have potential clinical impact. The original patient plan total Monitor Units
      (MUs) were correlated to the total number of dose metrics exceeded. RESULTS: The
      impact of different errors was consistent, with ap-VMAT plans (two institutions)
      showing larger dose deviations than mp-VMAT created plans (one institution).
      Across all institutions' VMAT plans the significant errors included; +/-5 degrees
      for the collimator angle, +/-5mm for the MLC shift and +1, +/-2 and +/-5mm for
      the MLC field size. The total number of dose metrics exceeding tolerance was
      positively correlated to the VMAT total plan MUs (r=0.51, p<0.001), across all
      institutions and techniques. CONCLUSIONS: Differences in VMAT robustness to
      simulated errors across institutions occurred due to planning method differences.
      Whilst ap-VMAT was most sensitive to MLC errors, it also produced the best
      quality treatment plans. Mp-ssIMRT was most robust to errors. Higher VMAT
      treatment plan complexity led to less robust plans.

PMID- 29173922
TI  - On the re-calibration process in radiochromic film dosimetry.
AB  - PURPOSE: The accuracy and precision of the dose estimates obtained with
      radiochromic film dosimetry are investigated in a clinical environment. The
      improvement in the accuracy of dose estimates reached with corrective methods is
      analyzed. Two novel re-calibration algorithms for radiochromic film dosimetry are
      presented. METHODS: Two different EBT3 lots are evaluated in two different
      centres. They are calibrated in Varian linacs and read in two different EPSON
      scaners. Once the lots are calibrated, three films per lot are considered and
      divided into stripes that are exposed to known doses. Several dosimetry protocols
      usually employed in radiochromic film dosimetry are used to convert film
      responses to absorbed doses. These protocols are characterized by different
      choices of the film responses or different sensitometric curves. Finally, the
      accuracy and reproducibility of the dose estimates is investigated with and
      without the corrective methods. RESULTS AND CONCLUSIONS: The variabilities that
      affect radiochromic film dosimetry, such as intra-lot variability, inter-scan
      variability, post-exposure time and film autodevelopment may give rise to
      inaccuracies in the dose estimates. However, the implementation of re-calibration
      methods leads to more accurate dose estimates. All the investigated protocols
      showed more accurate and reproducible results when the re-calibrated methods were
      employed. So, the novel re-calibration methods may be applied in order to improve
      the accuracy and reproducibility of radiochromic film dosimetry.

PMID- 29173923
TI  - Microdosimetry in 3D realistic mitochondria phantoms: Geant4 Monte Carlo tracking
      of 250keV photons in phantoms reconstructed from microscopic images.
AB  - Mitochondria are considered to be sensitive radiation targets since they control
      processes vital to the cell's functioning. These organelles are starting to get
      attention and some studies are investigating the radiation dose inside them. In
      previous studies, mitochondria are represented as simple ellipsoids inside the
      cell not taking into consideration the complexity of their shape. In this study,
      realistic phantoms are built based on deconvolved widefield fluorescent
      microscopic images of the mitochondrial networks of fibroblast cells. The
      phantoms are imported into Geant4 as tessellated volumes taking into account the
      geometrical complexity of these organelles. Irradiation with 250keV photons is
      performed and the lineal energy is calculated. The lineal energy distributions
      inside the produced phantoms are compared with those calculated inside simple
      volumes, a sphere and an ellipsoid, where the effect of the shape and volume is
      clearly seen on lineal energies.

PMID- 29173924
TI  - A review of GPU-based medical image reconstruction.
AB  - Tomographic image reconstruction is a computationally demanding task, even more
      so when advanced models are used to describe a more complete and accurate picture
      of the image formation process. Such advanced modeling and reconstruction
      algorithms can lead to better images, often with less dose, but at the price of
      long calculation times that are hardly compatible with clinical workflows.
      Fortunately, reconstruction tasks can often be executed advantageously on
      Graphics Processing Units (GPUs), which are exploited as massively parallel
      computational engines. This review paper focuses on recent developments made in
      GPU-based medical image reconstruction, from a CT, PET, SPECT, MRI and US
      perspective. Strategies and approaches to get the most out of GPUs in image
      reconstruction are presented as well as innovative applications arising from an
      increased computing capacity. The future of GPU-based image reconstruction is
      also envisioned, based on current trends in high-performance computing.

PMID- 29173925
TI  - Nuclear and radiological emergencies: Building capacity in medical physics to
      support response.
AB  - Medical physicists represent a valuable asset at the disposal of a structured and
      planned response to nuclear or radiological emergencies (NREs), especially in the
      hospital environment. The recognition of this fact led the International Atomic
      Energy Agency (IAEA) and the International Organization for Medical Physics
      (IOMP) to start a fruitful collaboration aiming to improve education and training
      of medical physicists so that they may support response efforts in case of NREs.
      Existing shortcomings in specific technical areas were identified through
      international consultations supported by the IAEA and led to the development of a
      project aiming at preparing a specific and standardized training package for
      medical physicists in support to NREs. The Project was funded through extra
      budgetary contribution from Japan within the IAEA Nuclear Safety Action Plan.
      This paper presents the work accomplished through that project and describes the
      current steps and future direction for enabling medical physicists to better
      support response to NREs.

PMID- 29173926
TI  - Measurement of the influence of titanium hip prosthesis on therapeutic electron
      beam dose distributions in a novel pelvic phantom.
AB  - PURPOSE: To investigate the degree of 18 and 22MeV electron beam dose
      perturbations caused by unilateral hip titanium (Ti) prosthesis. METHODS:
      Measurements were acquired using Gafchromic EBT2 film in a novel pelvic phantom
      made out of Nylon-12 slices in which a Ti-prosthesis is embedded. Dose
      perturbations were measured and compared using depth doses for 8*8, 10*10 and
      11*11cm2 applicator-defined field sizes at 95cm source-surface-distance (SSD).
      Comparisons were also made between film data at 100cm SSD for a 10*10cm2 field
      and dose calculations made on CMS XiO treatment planning system utilizing the
      pencil beam algorithm. The extent of dose deviations caused by the Ti prosthesis
      based on film data was quantified through the dose enhancement factor (DEF),
      defined as the ratio of the dose influenced by the prosthesis and the unchanged
      beam. RESULTS: At the interface between Nylon-12 and the Ti implant on the
      prosthesis entrance side, the dose increased to values of 21+/-1% and 23+/-1% for
      18 and 22MeV electron beams, respectively. DEFs increased with increasing
      electron energy and field size, and were found to fall off quickly with distance
      from the nylon-prosthesis interface. A comparison of film and XiO depth dose data
      for 18 and 22MeV gave relative errors of 20% and 25%, respectively. CONCLUSION:
      This study outlines the lack of accuracy of the XiO TPS for electron planning in
      highly heterogeneous media. So a dosimetric error of 20-25% could influence
      clinical outcome.

PMID- 29173927
TI  - Violence Research.

PMID- 29173928
TI  - The Community Impact Violence: A Time to Stop Killing.

PMID- 29173929
TI  - Lessons Learned from 50 Years of Violence Prevention Activities in the African
      American Community.
AB  - PURPOSE: This article covers violence prevention (homicide and suicide)
      activities in the African American community for nearly 50 years. METHOD: Drawing
      on lived experience the works of early and recent efforts by African American
      physicians, the author illustrates we know a great deal about violence prevention
      in the African American community. RESULTS: There remains challenges of
      implementation and political will. Further, most physicians, like the public, are
      confused about the realities of homicide and suicide because of the two different
      presentations both are given in the media and scientific literature. CONCLUSIONS:
      Responses to homicide and suicides should be based on science not distorted media
      reports. There are violence prevention principles that, if widely implemented,
      could stem the tide of violence.

PMID- 29173930
TI  - Birth Outcomes in Relation to Intimate Partner Violence.
AB  - OBJECTIVES: Intimate partner violence (IPV)during pregnancy is a significant
      public health problem. Approximately 324,000 IPV victimizations occur during
      pregnancy each year. However, research on the impact of IPV on birth outcomes
      yields conflicting findings. This study examines the association of IPV with
      birth outcomes among pregnant women. STUDY DESIGN: We used a retrospective cohort
      study design to analyze data from chart reviews of a random sample of 1542
      pregnant women. These women were seen between 2003 and 2009 at an urban
      university affiliated prenatal clinic and gave birth at the on-site hospital.
      Victims of IPV were defined as those who scored equal to or higher than 10 on an
      IPV screening tool: HITS (Hit, Insult, Threaten, and Scream). Three measures were
      included in birth outcomes. Preterm delivery was defined as gestational age less
      than 37 weeks. Low birth weight was defined as infants born weighing <2500 g.
      Neonatal intensive care was measured by prevalence of receiving intensive care.
      RESULTS: The prevalence of IPV was 7.5%. Compared to non-abused women, abused
      women were more likely to have preterm deliveries (18.3% vs. 10.3%; p = .016).
      Compared to infants of non-victims, infants of victims were more likely to have
      low birth weight (21.5% vs. 11.0%; p = .003) and to receive neonatal intensive
      care (23.4% vs. 7.8%; p = .000). Results from multivariate analyses indicated
      that victims were more likely to have preterm deliveries than non-victims (OR =
      1.72; 95% CI: 1.22-2.95). More infants of victims had low birth weight (OR =
      2.03; 95% CI: 1.22-3.39) and received neonatal intensive care than those of non
      victims (OR = 4.04; 95% CI: 2.46-6.61). CONCLUSIONS: Abused pregnant women had
      poorer birth outcomes compared to non-abused pregnant women. Healthcare providers
      should be trained to screen and identify women for IPV, and interventions should
      be designed to reduce and prevent IPV and thereby improve health outcomes for
      victims and their children.

PMID- 29173931
TI  - Infant Deaths and Mortality from Gun Violence: Causal or Casual?
AB  - OBJECTIVE: Describe trends in non-Hispanic black infant mortality (IM) in the New
      York City (NYC) counties of Bronx, Kings, Queens, and Manhattan and correlations
      with gun-related assault mortality. METHODS: Linked Birth/Infant Death data (1999
      2013) and Compressed Mortality data at ages 1 to >=85 years (1999-2013). NYC and
      United States (US) Census data for income inequality and poverty. Pearson
      coefficients were used to describe correlations of IM with gun-related assault
      mortality and other causes of death. RESULTS: In NYC, the risk of non-Hispanic
      black IM in 2013 was 49% lower than in 1995 (rate ratio: 0.51; 95% CI: 0.43,
      0.61). Yearly declines between 1999 and 2013 were significantly correlated with
      declines in gun-related assault mortality (correlation coefficient (r) = 0.70, p
      = 0.004), drug-related mortality (r = 0.59, p = 0.020), major heart disease and
      stroke (r = 0.85, p < 0.001), malignant neoplasms (r = 0.57, p = 0.026), diabetes
      mellitus (r = 0.63, p = 0.011), and pneumonia and influenza (r = 0.78, p <
      0.001). There were no significant correlations of IM with chronic lower
      respiratory or liver disease, non-drug-related accidental deaths, and non-gun
      related assault. Yearly IM (1995-2012) was inversely correlated with income share
      of the top 1% of the population (r = -0.66, p = 0.007). CONCLUSIONS: In NYC, non
      Hispanic black IM declined significantly despite increasing income inequality and
      was strongly correlated with gun-related assault mortality and other major causes
      of death. These data are compatible with the hypothesis that activities related
      to overall population health, including those pertaining to gun-related homicide,
      may provide clues to reducing IM. Analytic epidemiological studies are needed to
      test these and other hypotheses formulated from these descriptive data.

PMID- 29173932
TI  - Influence of Intimate Partner Violence (IPV) Exposure on Cardiovascular and
      Salivary Biosensors: Is There a Relationship?
AB  - BACKGROUND/PURPOSE: Intimate partner violence (IPV) is a global public health
      epidemic that initiates/exacerbates health consequences affecting a victim's
      lifespan. IPV can significantly predispose women to a lifetime risk of developing
      cardiovascular disease (CVD) due to the effects of stress and inflammation. This
      study investigates the correlation among IPV exposure, in-vivo CVD events, and
      inflammatory biomarkers as predictor indices(s) for CVD in female dental
      patients. METHODS: Of 37 women enrolled in this study, 19 were African-American
      (AA) and 18 non-African-American (non-AA) and their ages ranged from 19 to 63
      years. IPV-exposure and stress-induced in-vivo CVD events such as Chest Pain (CP)
      and Heart palpitations were recorded from all enrolled subjects. Cardiovascular
      events were obtained through surveys by patient self-report. Saliva specimens
      were obtained from all women and were analyzed for CVD biomarkers using multiplex
      ELISA. RESULTS: The prevalence of IPV was 51% (19/37) and statistically
      equivalent for AA and non-AA. The results show differences in experience of 1) CP
      (p < 0.01) and 2) heart palpitations (p < 0.02) when IPV + participants are
      compared with IPV- AA and non-AA cohorts. Of 10 CVD biomarkers analyzed,
      significant correlations between IPV+ and IPV- subjects were observed for
      biomarkers that include Interleukin-1beta/sCD40L; TNFalpha/sCD40L; Myoglobin/IL
      1beta; CRP/sCD40L; CRP/IL-6; CRP/TNFalpha; TNFalpha/siCAM; CRP/MMP9; TNF
      alpha/Adiponectin (p < 0.01). DISCUSSION/IMPLICATIONS: Analysis of in vivo CVD
      status showed that significant race/health disparities exist in IPV + cohorts, as
      well as increased expression of inflammatory mediators, specifically CRP, IL
      1beta, IL-6, MMP9. Women who have experienced IPV may be a target cohort for
      primary prevention of CVD. The use of salivary biomarkers and our protocol may
      provide a less invasive method to help increase identification of victims at risk
      for IPV and CVD and potentially decrease other health injuries associated with
      IPV exposure.

PMID- 29173933
TI  - Elder Abuse in the African Diaspora: A Review.
AB  - BACKGROUND: As with many other populations, abuse of older adults is a growing
      problem across the Africa Diaspora. Modernization and urbanization are eroding
      the traditional values of respect for older adults. Also, older adults living in
      environments with limited social and economic resources, and having no means of
      economic support create a recipe for elder abuse and neglect. METHODS: This
      article reviews the current literature on the epidemiology, risk factors, and
      interventions used for elder abuse across the African Diaspora. RESULTS: Reports
      of elder abuse range from 24.9% to 81.1% across the Diaspora. Risk factors
      include cognitive and physical impairment, social isolation, lack of resources
      and widowhood. CONCLUSION: Community-based programs using the unique social
      networks of older populations of African descent can provide a venue to improve
      caregiver training and support, reinforce traditional filial and informal
      caregiving practices, increase the utilization of available governmental and
      institutional.

PMID- 29173934
TI  - Methods and Findings from the National Violent Death Reporting System for
      Identifying Gang-Like Homicides, 2005-2008.
AB  - BACKGROUND: The National Violent Death Reporting System (NVDRS) captures
      homicides that law enforcement or coroner/medical examiners deem as gang-related
      but the criteria used may vary across locations. Also, the existing gang-related
      variable likely underestimates the number of homicides that are associated with
      gang activity. This study utilizes NVDRS data to identify "gang-like" homicides
      which are not currently captured as "gang-related." METHODS: A set of criteria
      recommended by a panel of experts in gang violence, was applied to homicides
      collected in the NVDRS. These criteria, termed "gang-like" characteristics, were
      developed in order to better identify homicides consistent with gang activity.
      The narratives of the identified cases were then reviewed to refine the
      operational standard. After the reviews were complete, the typology was modified
      to finalize the operationalization of "gang-like" homicides. RESULTS: A total of
      481 gang-like homicides were identified using the "gang-like" criteria. This
      represents an increase of almost 69% over the 696 gang-related homicides captured
      in NVDRS dataset. Gang-like and gang-related homicides combined represented 6.6%
      of homicides that occurred from 2005 to 2008. Among the 16 states included in
      this analysis, Colorado (15.5%) and Oklahoma (14%) had the highest percentage of
      homicides that were either gang-related or gang-like. Maryland had the greatest
      relative increase (227.3%) between gang related and gang-like homicides.
      CONCLUSION: The new "gang-like" variable complements the existing "gang-related"
      variable by providing an automated, standardized way to identify homicides that
      have circumstances consistent with gang activity. This new variable might be
      useful to states and localities seeking an efficient way to monitor homicides
      potentially resulting from gang activity. Additional efforts are needed to
      standardize the reporting of homicides associated with gang activity.

PMID- 29173935
TI  - Racial/Ethnic and Social Inequities in Sleep Medicine: The Tip of the Iceberg?
AB  - PURPOSE: It is known that racial disparities exist in terms of disease prevalence
      and access to health care. However, the link between race/ethnicity and sleep
      quality is often under-recognized. RESULTS: Current evidence shows that
      differences exist between Blacks and Whites in terms of sleep duration, sleep
      quality, and the likelihood of acquiring a sleep disorder. It has been argued
      that the adverse effects of ethnicity on sleep quality or duration interact with
      other social or personal factors (such as employment) and that the effects of
      these factors are interactive and need to be analyzed simultaneously. There is a
      growing body of evidence showing that disturbed sleep is a mediator of the effect
      of environmental stressors on personal health, which is more pronounced in ethnic
      minorities. CONCLUSIONS: These findings support the notion that perceived
      discrimination or unfair treatment has significant associations with complaints
      of sleep disturbance and disturbed objective measures of sleep quality and sleep
      architecture. Hence, greater efforts are needed to demonstrate how racial/ethnic
      factors influence different sleep processes.

PMID- 29173936
TI  - Factors Perceived to Influence the Decision for African Americans to Become
      Registered Organ Donors at the Department of Motorized Vehicles.
AB  - BACKGROUND: African Americans (AA) are a third as likely as Caucasians to become
      registered organ donors at the Department of Motorized Vehicles (DMV). The
      Department of Health and Human Services has set the goal that at least 50% of
      adults in each state are registered donors. AIMS: The purpose of this study was
      to explore the personal, behavioral and environmental factors associated with AA
      donor registration decision-making at the DMV. METHODS: Guided by the Social
      Cognitive Theory, 13 focus groups (n = 100 participants) were conducted with AAs
      within 3 months of visiting a DMV and making a decision regarding whether to
      become or to not become a registered donor. The data were analyzed using
      inductive thematic and qualitative content analyses. RESULTS: Study participants
      expressed a desire to learn more information while waiting in line at the DMV.
      Knowing a family member or friend in need of an organ transplant, and the desire
      to make one's own decision were two salient factors associated with the decision
      to become a registered organ donor. Several aspects of the DMV environment (e.g.,
      noisy, overcrowded, lacking privacy) were cited as deterrents to becoming a
      registered donor. DISCUSSION: This study highlights the personal, behavioral and
      environmental factors associated with AA organ donor registration decision-making
      at the DMV. CONCLUSION: The DMV is a setting where many adults make a decision
      about organ donation. Policies that create an environment in the DMV to support
      informed decision-making (e.g., privacy, informed clerks, available educational
      materials, etc.) are indicated.

PMID- 29173937
TI  - Relationship between Ultrasonic Marker of Fetal Lung Maturity and Lamellar Body
      Count.
AB  - BACKGROUND: The aim of this study was prediction the fetal lung maturity by
      ultrasonic markers and comparison by lamellar body count and fetal outcome.
      METHODS: A prospective Longitudinal study Department of perinatology of performed
      Emam Khomeini hospital and Mirza Kochak Khan Hospital in Tehran, Iran from March
      2013 to January 2014. 100 pregnant women (37-40 weeks of gestation) who were
      admitted for elective cesarean section and referred for an obstetric ultrasound
      scan at the same day of their elective cesarean section were included. Scanning
      with linear ultrasound with convex transducer frequency of 3.5 MHZ was utilized
      to measure the biparietal diameter, Amniotic fluid vernix and placental grading.
      Statistical analysis was performed using Spss version 20. Validity of the
      indicators compared with lamellar body count and fetal outcome. RESULTS: In this
      study, from 100 patients under study, 8 cases were hospitalized in NICU (neonatal
      intensive care unit) which all of them had LAMELAR BODY COUNT < 14000 (10000
      14000). There were 6 boys and 2 girls. In this study, there was no perinatal
      mortality. CONCLUSIONS: In study we used ultrasonic marker of fetal lung maturity
      and related this to lamellar body count and neo natal outcome. The ultrasonic
      marker of fetal lung maturity can reduce mortality and morbidity in neonate.

PMID- 29173938
TI  - Evaluation of Incidental Thyroid Nodules in Cancer Patients.
AB  - OBJECTIVE: Frequency of thyroid cancer in incidental thyroid nodules identified
      by imaging techniques in cancer patients is higher than that in the normal
      population. In the retrospective study, we have both investigated the incidence
      of thyroid cancer in incidentally identified nodules and compared the imaging
      techniques to determine whether there is any difference between them in detection
      of malign nodules. METHODS: A total of 7319 patients who underwent thyroid fine
      needle aspiration biopsy (FNAB) were included in the study. The data of 174
      patients who had previously been diagnosed with a hematologic or solid malignancy
      prior to the FNAB procedure and had incidentally identified thyroid nodules were
      evaluated retrospectively. RESULTS: Eighty-six (49.5%) of the incidental nodules
      were identified with ultrasonography (USG), 62 (35.6%) with positron emission
      tomography (PET) or PET/computed tomography (PET/CT), and 26 (14.9%) with CT. As
      a result of thyroidectomy, papillary carcinoma was identified in 8 (4.6%)
      patients, and metastasis to the thyroid of a primary cancer was found in 3 (1.7%)
      patients. While the papillary carcinoma proportion in the nodules identified by
      USG was 3.4%, PET/CT was 8.9%. A cut-off maximal standardized uptake value of
      11.6 in PET/CT indicated malignancy achieving a sensitivity of 83.3% and a
      specificity of 91.1%. CONCLUSION: Whether the nodule in the incidental thyroid
      nodules of cancer patients is identified using USG or PET/CT, the risk of thyroid
      cancer is similar. However, cancer risk is higher in the event of a higher focal
      uptake in the nodules identified by PET/CT.

PMID- 29173939
TI  - Wire rope tension control of hoisting systems using a robust nonlinear adaptive
      backstepping control scheme.
AB  - This paper concerns wire rope tension control of a double-rope winding hoisting
      system (DRWHS), which consists of a hoisting system employed to realize a
      transportation function and an electro-hydraulic servo system utilized to adjust
      wire rope tensions. A dynamic model of the DRWHS is developed in which parameter
      uncertainties and external disturbances are considered. A comparison between
      simulation results using the dynamic model and experimental results using a
      double-rope winding hoisting experimental system is given in order to demonstrate
      accuracy of the dynamic model. In order to improve the wire rope tension
      coordination control performance of the DRWHS, a robust nonlinear adaptive
      backstepping controller (RNABC) combined with a nonlinear disturbance observer
      (NDO) is proposed. Main features of the proposed combined controller are: (1)
      using the RNABC to adjust wire rope tensions with consideration of parameter
      uncertainties, whose parameters are designed online by adaptive laws derived from
      Lyapunov stability theory to guarantee the control performance and stability of
      the closed-loop system; and (2) introducing the NDO to deal with uncertain
      external disturbances. In order to demonstrate feasibility and effectiveness of
      the proposed controller, experimental studies have been conducted on the DRWHS
      controlled by an xPC rapid prototyping system. Experimental results verify that
      the proposed controller exhibits excellent performance on wire rope tension
      coordination control compared with a conventional proportional-integral (PI)
      controller and adaptive backstepping controller.

PMID- 29173940
TI  - Lymph node stromal and vascular proliferations.
AB  - The recognition and reporting of stromal and vascular lesions of the lymph node
      is rife with difficulties including relative rarity, a lack of familiarity with
      lesions and the challenges of using ancillary studies appropriately. In this
      manuscript, we highlight a range of benign stromal and vascular abnormalities
      that can be identified in nodal specimens.

PMID- 29173941
TI  - 150th anniversary of the Bethel epilepsy center in Germany: An important
      milestone in the evolution of epilepsy care.

PMID- 29173943
TI  - Feasibility of Using a Community-Supported Agriculture Program to Increase Access
      to and Intake of Vegetables among Federally Qualified Health Center Patients.
AB  - OBJECTIVE: This study explored the feasibility of using a 23-week subsidized
      community-supported agriculture program to increase access to and intake of
      vegetables among Federally Qualified Health Center patients. METHODS: Outcomes
      were measured using pre-post intervention surveys (n = 9). Process data were
      collected in post-intervention surveys and focus groups (n = 15). RESULTS: Most
      participants (77%) indicated that the program improved their health and all
      (100%) reported that they were eating a greater variety of vegetables because of
      their participation in the program. Three themes emerged from the focus groups:
      increased access to fresh and/or organic vegetables, improved diet quality, and
      the importance of social support during the program. CONCLUSIONS AND
      IMPLICATIONS: Linking subsided community-supported agriculture programs with
      Federally Qualified Health Centers has the potential to increase access to and
      intake of vegetables among low-income patients. However, further research is
      needed with a larger sample size and a more robust study design.

PMID- 29173942
TI  - Establishing consensus on survey measures for electronic nicotine and non
      nicotine delivery system use: Current challenges and considerations for
      researchers.
AB  - The development and validation of survey measures for electronic nicotine and non
      nicotine delivery system (ENDS) use has not kept pace with the burgeoning
      research on them. This, along with the diverse and evolving nature of ENDS,
      presents several unique measurement challenges and hampers surveillance and
      tobacco regulatory research efforts. In this commentary, we identify four
      important areas related to ENDS use (describing ENDS products; defining current
      use; evaluating frequency and quantity of use; and characterizing devices and e
      liquids) and summarize a selective review of the measurement and definitions of
      these constructs across prominent national tobacco use surveys and 30 projects
      within the 14 federally-funded Tobacco Centers of Regulatory Science. Across
      these national, regional, and local studies, there was considerable variability
      and relatively little consensus in ENDS use measures - thus highlighting the need
      for caution when comparing findings across studies or over time until more
      research is available to evaluate the sensitivity of findings to differing
      measures. Drawing from the nascent ENDS use measurement research literature and
      our experiences, we conclude with general considerations for measuring ENDS use
      for tobacco researchers as an initial step towards the development of consensus
      measures.

PMID- 29173944
TI  - Isosteric ribavirin analogues: Synthesis and antiviral activities.
AB  - The novel isosteric ribavirin analogues were synthesized by two different ways.
      Some of them showed significant antiviral action against hepatitis C virus (HCV),
      herpes simplex (HCV-1) and influenza A virus comparable to that of ribavirin
      itself. The data obtained confirm the proposed theory of the ribavirin possible
      antiviral activity mechanism related with bioisosterism.

PMID- 29173945
TI  - Synthesis and in vitro evaluations of 6-(hetero)-aryl-imidazo[1,2-b]pyridazine-3
      sulfonamide's as an inhibitor of TNF-alpha production.
AB  - Tumor necrosis factor-alpha is an important pro-inflammatory cytokine having a
      key role in hosts defensive process of immune systems and its over expression led
      to a diverse range of inflammatory diseases such as Rheumatoid arthritis, Cronh's
      disease, psoriasis, etc. This paper describes our medicinal chemistry efforts on
      imidazo[1,2-b]pyridazine scaffold: design, synthesis and biological evaluation.
      By the introducing sulfonamide functionality at 3 positions and substituting 6
      positions with (hetero)-aryl groups', a small library of compounds was prepared.
      All synthesized compounds were screened for lipopolysaccharide (LPS) mediated TNF
      alpha production inhibitory activity. Biological data revealed that the majority
      of the compounds of this series showed moderate to potent TNF-alpha production
      inhibitory activity. Compound 5u and 5v are the most potent compounds from the
      series with activity of IC50 = 0.5 uM and 0.3 uM respectively. A short SAR
      demonstrates that 3-sulfonyl-4-arylpiperidine-4-carbonitrile moiety on
      imidazo[1,2-b]pyridazine showed better activity compared to the 3-(4
      aryllpiperazin-1-yl) sulfonyl) in hPBMC assay. The molecular modeling studies
      revealed that the potent TNF-alpha production inhibitory activity 5v due to the
      extra stability of complex because of an extra pi-pi (pi-pi) stacking, hydrogen
      bonding interactions.

PMID- 29173946
TI  - Jumping from Association to Causation and Relying on Intermediate Outcomes Are
      Hazardous.

PMID- 29173947
TI  - A Negative Finding on Digital Rectal Examination Reduces the Need for Endoscopy?

PMID- 29173948
TI  - Rectal Examination May Not be Necessary in Gastrointestinal Bleeding.

PMID- 29173949
TI  - The Reply.

PMID- 29173950
TI  - Alternative Trends Estimate and Stakeout Synthetic Marijuana Use.

PMID- 29173951
TI  - The Reply.

PMID- 29173952
TI  - Corrigendum to "Advanced morphological neuroimaging study in lateral temporal
      lobe epilepsy: A multicentric study" [Epilepsy Behav 74 (2017) Pages 69-72].

PMID- 29173953
TI  - Corrigendum to "Acid-base reaction-based dispersive liquid-liquid microextraction
      method for extraction of three classes of pesticides from fruit juice samples"
      [J. Chromatogr. A 1431 (2016) 8-16].

PMID- 29173954
TI  - Novel thin-layer chromatographic method of screening the anthocyanes containing
      alimentary products and precautions taken at the method development step.
AB  - The purpose of this study was to develop a novel and cost-effective thin-layer
      chromatographic method (TLC) using cellulose powder as stationary phase for
      authentication of the selected fruit-based alimentary products and targeting
      anthocyanes as the authenticity markers. Our method outperformed the HPTLC method
      earlier developed by another research team using silica gel as stationary phase.
      It was demonstrated that due to a limited chemical stability of anthocyanes,
      employing them as authenticity markers is burdened with a non-negligible
      uncertainty risk. Hydrolytic split of the glycosides into the aglycone and
      carbohydrate moieties can lead to a confusing multiplication of chromatographic
      bands and therefore it is advisable to use for the authentication purposes a
      limited set of well selected and stable enough anthocyane markers. Cyanin
      chloride, keracyanin chloride, pelargonidin chloride and delphinidin chloride
      were selected as the external standards and for the development of the
      calibration curves. The TLC-obtained LOD and LOQ values were 0.025 and
      0.075MUgspot-1 for cyanin, 0.055 and 0.166MUgspot-1 for keracyanin, 0.047 and
      0.140MUgspot-1 for pelargonidin, and 0.171 and 0.513MUgspot-1 for delphinidin,
      respectively. The analogous HPTLC-obtained LOD and LOQ values were 0.107 and
      0.321MUgspot-1 for cyanin, 0.189 and 0.566MUgspot-1 for keracyanin, and 0.161 and
      0.484MUgspot-1 for pelargonidin, respectively. Delphinidin was not detectable
      with use of the HPTLC method. Consequently, quantification of anthocyanes in the
      alimentary products carried out with use of TLC allowed identification of more
      target compounds and in a higher number of alimentary products than it was
      possible with use of HPTLC, apparently due to the LOD levels by one magnitude
      order lower for TLC than HPTLC.

PMID- 29173955
TI  - Speedy standing wave design and simulated moving bed splitting strategies for the
      separation of ternary mixtures with linear isotherms.
AB  - Simulated Moving Bed (SMB) has advantages over batch chromatography in terms of
      productivity and solvent efficiency. However, SMB applications in large scale
      production are still limited because of the many design parameters that must be
      specified and the multiple splitting strategies that can be implemented. To
      overcome these barriers, this study extends the Speedy Standing Wave Design
      (SSWD) method of Weeden and Wang for binary linear systems to ternary linear
      adsorption systems. The dimensionless operating parameters, sorbent productivity,
      and solvent efficiency can be quickly calculated without process simulations.
      SSWD also gives an overview of the productivity and solvent efficiency as a
      function of two key dimensionless groups. This overview can be used for
      optimization of separation costs and for comparison of splitting strategies. The
      SSWD method was verified using rate model simulations for the separation of three
      amino acids. The simulated yields agree with the SSWD target yields within 1% for
      all components. The example was also used to illustrate the key design rules for
      ternary separations. High productivity and solvent efficiency can be achieved
      with a large difference in the retention factors of the heavy key and light key,
      which are the components that define the split of the feed between extract and
      raffinate products. For ternary ideal systems, solvent efficiency is inversely
      proportional to the largest difference in retention factors. For this reason,
      minimizing the overall range of retention factors can significantly improve the
      solvent efficiency and product concentration without sacrificing productivity. If
      more than one SMB is needed, the easiest split should be done first for higher
      productivity, solvent efficiency, and product concentration. In the example case
      study, both the productivity and solvent efficiency were about an order of
      magnitude higher when the easiest split was done in the first ring. The SSWD
      method can be used to design a wide array of multi-component separations with
      high yield, productivity, and solvent efficiency.

PMID- 29173956
TI  - Corrigendum to "Development of a new microextraction method based on elevated
      temperature dispersive liquid-liquid microextraction for determination of
      triazole pesticides residues in honey by gas chromatography-nitrogen phosphorus
      detection" [J. Chromatogr. A 1347 (2014) 8-16].

PMID- 29173957
TI  - A review on chiral separation by counter-current chromatography: Development,
      applications and future outlook.
AB  - Chiral separation has been a remarkably active area of research over the past
      long time and it still stays that way. Over the last few decades, counter-current
      chromatography (CCC) was successfully applied to the field of chiral separation.
      It provides an attractive approach to obtain pure enantiomer, particularly in
      preparative application because of its unique advantages of high load capacity,
      low solvent consumption and easy scale-up. The last several years great strides
      have been made in chiral separation by CCC, ranging from novel elution modes such
      as recycling elution mode and multiple dual mode elution to more specialized
      approaches such as pH-zone-refining and biphasic chiral recognition technologies.
      These developments have greatly improved the resolution of enantiomers and
      promoted the application of CCC in the field of chiral separation. Although not
      as popular as its application to the field of separation of natural product, the
      development of chiral separation by CCC should not be underrated. In this review
      article, we refer to the development, applications and future outlook of chiral
      separation by CCC, with emphasis on topics of its history, mechanism, advantages,
      limitations, current development and challenges. Meanwhile, its orientation of
      continued evolution and future outlook also have been discussed. While some
      scientific and technological problems have not yet been solved thoroughly, chiral
      separation by CCC has demonstrated potential advantages and prospects in this
      field and has good chance at preparative enantioseparation.

PMID- 29173958
TI  - Ion-pairing reversed-phase chromatography coupled to inductively coupled plasma
      mass spectrometry as a tool to determine mercurial species in freshwater fish.
AB  - Most of analytical community is focused on reversed phase high performance liquid
      chromatography (RP-HPLC) for mercury speciation by employing mobile phases
      comprising of high salts and moderate amounts of organic solvents. This study
      aims at rapid mercury speciation analysis by ion-pairing RP-HPLC with inductively
      coupled plasma mass spectrometry (ICP-MS) detection only using low salts for the
      sake of green analytical chemistry. Two ion-pairing HPLC methods were developed
      on individual usage of positively and negatively charged ion-pairing reagents
      (tetrabutylammonium hydroxide -TBAH and sodium dodecylbenzene sulfonate -SDBS),
      where sodium 3-mercapto-1-propysulfonate (MPS) and l-cysteine (Cys) were
      individually added in mobile phases to transform mercury species into negative
      and positive Hg-complexes for good resolution. Addition of phenylalanine was also
      utilized for rapid baseline separation in combination of short C18 guard columns.
      Optimum mobile phases of 2.0mM SDBS+2.0mM Cys+1.0mM Phe (pH 3.0) and 4.0mM
      TBAH+2.0mM MPS+2.0mM Phe (pH 6.0) both achieved baseline separation of inorganic
      mercury (Hg2+), methylmercury (MeHg), ethylmercury (EtHg) and phenylmercury
      (PhHg) on two consecutive 12.5-mm C18 columns. The former mobile phase was
      selected for mercury speciation in freshwater fish because of short separation
      time (3.0min). Detection limits of 0.015 for Hg2+, 0.014 for MeHg, 0.028 for EtHg
      and 0.042MUgL-1 for PhHg were obtained along with satisfactory precisions of peak
      height and area (1.0-2.8% for 5.0MUgL-1 Hg-mixture standard). Good accordance of
      determined values of MeHg and total mercury in certified reference materials of
      fish tissue (GBW 10029) and tuna fish (BCR-463) with certified values as well as
      good recoveries (91-106%) proved good accuracy of the proposed method. An example
      application to freshwater fish indicated its potential in routine analysis, where
      MeHg was presented at 3.7-20.3MUgkg-1 as the dominate species.

PMID- 29173959
TI  - Aspects influencing patients' preferences for the management of drug-drug
      interactions: A focus group study.
AB  - OBJECTIVE: The management of drug-drug interactions (DDIs) involves a complex
      risk-benefit assessment, in which patients' preferences should be taken into
      account. The aim of this study was to examine the aspects influencing patients'
      preferences with regard to DDI management options. METHODS: A qualitative study
      consisting of five focus groups with patients chronically using cardiovascular
      drugs was conducted. Key questions concerned preferences regarding DDI management
      options for a provided fictitious DDI. Thematic analysis of the verbatim
      transcripts was performed. RESULTS: Despite their limited knowledge with respect
      to DDIs, patients easily chose a management option for the presented DDI. When
      additional information was provided, preferences showed to be fluid. Ten
      interdependent aspects influencing preferences were derived from patients'
      argumentations: risk perception, fear, acceptance of uncertainty, openness to
      change, willingness to take risk, trust in health care professional, financial &
      practical burdens, health condition, experience, and knowledge & assumptions.
      CONCLUSION: Patients' preferences regarding DDI management options were often
      determined by provided information. Preferences were dependent on an interplay of
      diverse aspects. PRACTICE IMPLICATIONS: Tailored provision of information and
      individualized counseling is needed for active patient involvement in DDI
      decision making.

PMID- 29173960
TI  - Face-to-face communication between patients and family physicians in Canada: A
      scoping review.
AB  - OBJECTIVE: Patient-provider communication is critical in primary care. Canada's
      unique health system, population distribution, and cultural context suggest there
      is value in addressing the topic in the Canadian context. We conducted a scoping
      review to synthesize recent Canadian literature to inform practice in primary
      care settings and identify research agendas for patient-provider communication in
      Canada. METHODS: Using Arksey and O'Malley's framework we searched four
      literature databases: Medline, Web of Science, CINAHL and EMBASE. We extracted
      21,932 articles published between 2010 and 2017. A total of 108 articles met the
      inclusion criteria. The articles were analyzed qualitatively using thematic
      analysis to identify major themes. RESULTS: Four major themes were identified:
      information sharing, relationships, health system challenges, and development and
      use of communication tools. CONCLUSION: Our review identified a need for Canadian
      research regarding: communication in primary care with Aboriginal, immigrant, and
      rural populations; the impact of medical tourism on primary care; and how to
      improve communication to facilitate continuity of care. PRACTICE IMPLICATIONS:
      Challenges providers face in primary care in Canada include: communicating with
      linguistically and culturally diverse populations; addressing issues that emerge
      with the rise of medical tourism; a need for decision aids to improve
      communication with patients.

PMID- 29173961
TI  - Direct adaptive robust tracking control for 6 DOF industrial robot with enhanced
      accuracy.
AB  - A direct adaptive robust tracking control is proposed for trajectory tracking of
      6 DOF industrial robot in the presence of parametric uncertainties, external
      disturbances and uncertain nonlinearities. The controller is designed based on
      the dynamic characteristics in the working space of the end-effector of the 6 DOF
      robot. The controller includes robust control term and model compensation term
      that is developed directly based on the input reference or desired motion
      trajectory. A projection-type parametric adaptation law is also designed to
      compensate for parametric estimation errors for the adaptive robust control. The
      feasibility and effectiveness of the proposed direct adaptive robust control law
      and the associated projection-type parametric adaptation law have been
      comparatively evaluated based on two 6 DOF industrial robots. The test results
      demonstrate that the proposed control can be employed to better maintain the
      desired trajectory tracking even in the presence of large parametric
      uncertainties and external disturbances as compared with PD controller and
      nonlinear controller. The parametric estimates also eventually converge to the
      real values along with the convergence of tracking errors, which further validate
      the effectiveness of the proposed parametric adaption law.

PMID- 29173962
TI  - Intraoperative lateral wall fractures during Dynamic Hip Screw fixation for
      intertrochanteric fractures-Incidence, causative factors and clinical outcome.
AB  - INTRODUCTION: The intact lateral wall plays a key role in stabilization of
      trochanteric fracture. Hence extreme precaution should be taken to prevent
      lateral wall damage during DHS fixation. Present study is aimed at evaluating the
      determinants of lateral wall fracture and its effect on outcome in
      intertrochanteric fracture femur treated with DHS. MATERIAL AND METHODS: This is
      a prospective study involving intertrochanteric fractures treated with DHS
      fixation from July 2013 to June 2014. Out of 135 patients 49(36.3%) had stable
      fractures and 86(63.7%) unstable fractures. Cortical thickness index (CTI) was
      measured to evaluate osteoporosis. Lateral wall thickness in anteroposterior
      radiograph was also measured.All patients underwent 135 degrees  DHS
      fixation.Postoperative x-rays are assessed for implant position, intactness of
      the lateral wall, tip apex distance (TAD) and medialization. Functional outcome
      was measured at the end of fracture union by modified Harris hip score and
      Parkers mobility score. Clinical information including age, gender, fracture
      classification, TAD, lateral wall thickness and functional outcome of the
      patients were subjected to statistical analysis. RESULTS: 34 (19.5%) patients had
      lateral wall fractures. Medialization was found in 22 out of these 34 (64.7%)
      patients. The mean preoperative lateral wall thickness of these patients is
      19.2mm, compared with 26.8mm in patients with intact lateral wall (p<0.001). The
      mean values of CTI and TAD are comparable in both the groups. In patients with
      intact lateral wall, mean Harris hip score is 73.1 compared to 65.5 in lateral
      wall fracture group (p<0.001). Preinjury mobility status was achieved in 70.2% of
      intact lateral wall patients, whereas only 32.3% (11) achieved that in lateral
      wall fracture group. Threshold for lateral wall thickness that could predict
      lateral wall fracture was found to be 21mm with 95% sensitivity and 88.2%
      specificity. CONCLUSION: Lateral wall fractures during DHS fixation are not
      uncommon and osteoporosis has no bearing on its occurrence. It alone can lead to
      poor radiological and functional outcome independent of TAD. Lateral wall
      thickness is a reliable predictor of intra operative lateral wall fracture during
      DHS fixation and nailing is a good option especially when lateral wall thickness
      is <21mm.

PMID- 29173963
TI  - Acute Kidney Injury: It's not just the 'big' burns.
AB  - BACKGROUND: Acute Kidney Injury (AKI) complicates the management of at least 25%
      of patients with severe burns and is associated with long term complications.
      Most research focuses on the patients with more severe burns, and whether the
      same factors are associated with the development of AKI in patients with burns
      between 10 and 19% total body surface area (TBSA) is unknown. The aims of this
      study were to examine the incidence of, and factors associated with, the
      development of AKI in patients with %TBSA>=10, as well as the relationship with
      hospital metrics such as length of stay (LOS). METHODS: Retrospective medical
      record review of consecutive burns patients admitted to The Alfred Hospital, the
      major adult burns centre in Victoria, Australia. Demographic and injury details
      were recorded. Factors associated with AKI were determined using multiple
      logistic regression. RESULTS: Between 2010 and June 2014, 300 patients were
      admitted with burn injury and data on 267 patients was available for analysis.
      Median age was 54.5 years with 78% being male. Median %TBSA was 15 (IQR 12, 20).
      The AKI incidence, as measured by the RIFLE criteria, was 22.5%, including 15%
      (27/184) in patients with %TBSA 10-19. Factors associated with AKI included
      increasing age and %TBSA (OR 1.05 p<0.001) as well as increased surgeries
      (p<0.041) and a cardiac comorbidity (p<0.01). All patients with renal comorbidity
      developed AKI. In the %TBSA 10-19 cohort, only increasing age (OR 1.05 p<0.001)
      was associated with AKI. After accounting for confounding factors, the
      probability of discharge from hospital in Non-AKI group was greater than for the
      AKI patients at all time points (P<0.001). CONCLUSION: This is the first study to
      show an association between patients with %TBSA 10-19 and AKI. Given the
      association between AKI and complications, prospective research is needed to
      further understand AKI in burns with the aim of risk reduction.

PMID- 29173964
TI  - Outcomes after resection versus non-resection management of penetrating grade III
      and IV pancreatic injury: A trauma quality improvement (TQIP) databank analysis.
AB  - BACKGROUND: High-grade traumatic pancreatic injuries are associated with
      significant morbidity and mortality. Non-resection management is associated with
      fewer complications in pediatric patients. The present study evaluates outcomes
      following resection versus non-resection management of severe pancreatic injury
      caused by penetrating trauma. METHODS: A retrospective study of the Trauma
      Quality Improvement Program (TQIP) database was performed from 1/2010 to 12/2014.
      Patients with AAST Organ Injury Scale pancreatic grade III and IV injuries caused
      by penetrating trauma were included in the study. Demographics, vital signs on
      admission, Abbreviated Injury Scale per body region, Injury Severity Score,
      transfusion and therapeutic modality were obtained. Mortality, length of stay
      (LOS), pseudocyst, pancreatitis, sepsis, thromboembolism, renal failure, ARDS and
      unplanned ICU admission or re-operation were stratified according to injury grade
      and treatment modality. Patients were stratified into those who did/did not
      undergo pancreatic resection. RESULTS: A total of 4,098 patients had a pancreatic
      injury of which 15.9% (n=653) had a grade III and 6.7% (n=274) a grade IV
      pancreatic injury. There were no differences in patient demographics or overall
      injury severity between the resected and non-resected cohorts within each
      pancreatic injury grade. Forty-two percent of grade III and 38.0% of grade IV
      injuries underwent pancreatic resection. The total LOS was longer in the
      resection arm irrespective of pancreatic injury severity. There was no
      significant difference in morbidity between cohorts. Similarly, mortality was not
      significantly different between the two management approaches for grade III:
      15.1% (95% CI 11.0-19.9) vs. 18.4% (95% CI 14.6-22.6), p=0.32 and grade IV: 24.0%
      (95% CI: 16.2-33.4) vs. 27.1% (95% CI: 20.5-34.4), p=0.68. CONCLUSION: Resection
      for treatment of grade III and IV pancreatic injury is not associated with a
      significant decrease in mortality but is associated with an increase in hospital
      LOS.

PMID- 29173965
TI  - Complications and patient-injury after ankle fracture surgery. -A closed claim
      analysis with data from the Patient Compensation Association in Denmark.
AB  - BACKGROUND: The Patient Compensation Association (PCA) receives claims for
      financial compensation from patients who believe they have sustained damage from
      their treatment in the Danish health care system. In this study, we have analysed
      closed claims in which patients suffered injuries due to the surgical treatment
      of their ankle fracture. We identified causalities contributing to these injuries
      and malpractices, as well as the economic consequences of these damages. METHODS:
      Fifty-one approved closed claims from the PCA database from the years 2004-2009
      were analysed in a retrospective systematic review. All patients were adults with
      an iatrogenic injury, and received compensation. A root cause analysis was
      performed to identify whether the patient suffered the damage preoperatively,
      during surgery or postoperatively, and to determine the level of education of the
      injurious doctor. Economic compensation, co-morbidities and end-result
      complications were registered. RESULTS: In 9 of the cases the injuries happened
      preoperatively, but the majority of the injuries, namely 34 occurred during
      surgery. In 21 of the cases the damage happened postoperatively. Thirty
      percentages of the patients were mistreated in more than one phase. Level of
      competence was medical specialists in 2/3 and junior doctors in 1/3 of the cases.
      In the preoperative phase both groups were equally responsible for the inflicted
      damage. In the perioperative- and postoperative group, medical specialists
      inflicted the majority of damages. General recommendations regarding ORIF were
      not followed in 21/49 of the perioperative damages. The pronation fracture was
      the most common. The patients received a total average compensation of 17.561 USD
      each. CONCLUSION: Managing the complex ankle fracture, requires considerable
      experience. This study indicates that extra attention should be paid to the most
      technically demanding fractures as the pronation-external-rotation-, diabetic-
      and fragility fractures. Surgeons should follow the recommendations for ORIF.
      Emphasis should also focus on adequate postoperative plans. This study finds a
      high readmission-burden, re-operation rate and great expenses in form of
      compensation.

PMID- 29173966
TI  - Sometimes we can see some mental states: Comment on "Seeing mental states: An
      experimental strategy for measuring the observability of other minds" by Cristina
      Becchio, Atesh Koul, Caterina Asuini, Cesare Bertone, and Andrew Cavallo.

PMID- 29173967
TI  - Biosynthesis of polyhydroxyalkanoates containing 2-hydroxy-4-methylvalerate and 2
      hydroxy-3-phenylpropionate units from a related or unrelated carbon source.
AB  - The discovery of the lactate-polymerizing enzyme (LPE) enabled the biosynthesis
      of a polyhydroxyalkanoate (PHA) containing 2-hydroxyalkanoate (2HA). Amino acids
      are potential precursors of 2HA with various side chain structures if appropriate
      enzymes are used to convert amino acids to 2HA-coenzyme A (CoA) as the substrate
      for LPE. In this study, the suitability and utility of (R)-2-hydroxy-4
      methylvalerate (2H4MV) dehydrogenase (LdhA) and 2H4MV-CoA transferase (HadA) from
      Clostridium difficile as 2HA-CoA-supplying enzymes were investigated. By
      expressing LPE, LdhA, and HadA in Escherichia coli DH5alpha, we successfully
      produced poly(3-hydroxybutyrate-co-2HA) [P(3HB-co-2HA)] from a related or
      unrelated carbon source. The 2HA units incorporated into PHA from unrelated
      carbon sources were primarily 2H4MV and 2-hydroxy-3-phenylpropionate (2H3PhP),
      which were assumed to be derived from endogenous leucine and phenylalanine,
      respectively. Furthermore, P(3HB-co-22 mol% 2HA) synthesis was demonstrated by
      means of saccharified sugars, which are an abundant and renewable feedstock for
      polymer production from hemicellulosic biomass (Japanese cedar) as the carbon
      source. Our study shows that several types of 2HA units such as 2H4MV and 2H3PhP
      are endogenous monomers for PHA biosynthesis in E. coli expressing LdhA and HadA.

PMID- 29173968
TI  - Causality test of ambient fine particles and human influenza in Taiwan: Age group
      specific disparity and geographic heterogeneity.
AB  - Influenza is a major global public health problem, with serious outcomes that can
      result in hospitalization or even death. We investigate the causal relationship
      between human influenza cases and air pollution, quantified by ambient fine
      particles <2.5MUm in aerodynamic diameter (PM2.5). A modified Granger causality
      test is proposed to ascertain age group-specific causal relationship between
      weekly influenza cases and weekly adjusted accumulative PM2.5 from 2009 to 2015
      in 11 cities and counties in Taiwan. We examine the causal relationship based on
      posterior probabilities of the log-linear integer-valued GARCH (generalized
      autoregressive conditional heteroscedastic) model with covariates, which enable
      us to handle characteristics of influenza data such as integer-value, lagged
      dependence, and over-dispersion. The resulting posterior probabilities show that
      the adult age group (25-64) and the elderly group in New Taipei in the north and
      cities in southwestern part of Taiwan are strongly affected by ambient fine
      particles. Moreover, the elderly group is clearly affected in all study sites.
      Globalization and economic growth have resulted in increased ambient air
      pollution (including PM2.5) and subsequently substantial public health concerns
      in the West Pacific region. Minimizing exposure to air pollutants is particularly
      important for the elderly and susceptible individuals with respiratory diseases.

PMID- 29173969
TI  - The Dreadful Knowledge of Truth: Newborn Screening in the Modern Age.

PMID- 29173970
TI  - Answer to The incidence and clinical associated factors of interval colorectal
      cancers in Southern Taiwan: Methodological issues.

PMID- 29173971
TI  - Beyond bystanders: Myeloid cells in chronic lymphocytic leukemia.
AB  - Tumor-promoting inflammation and escape from immune-mediated tumor destruction
      have been recognized as hallmarks of cancer, and myeloid cells are key players in
      these processes. By exploiting the tremendous plasticity of myeloid cells, tumors
      induce a variety of tumor-supportive and immunosuppressive cell phenotypes like
      tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs).
      The relevance of these cell types in hematopoietic malignancies has only recently
      gained a stronger attention. Chronic lymphocytic leukemia (CLL) is a malignancy
      of mature B cells that expand in secondary lymphoid organs and the bone marrow,
      and accumulate in the blood of patients. A large body of evidence suggests that
      the interactions between CLL cells and non-malignant cells in the tumor
      microenvironment play a key role in the pathology of this disease. CLL is
      associated with an inflammatory milieu and defective immune responses. A severe
      skewing of myeloid and T cells toward leukemia-supportive and immunosuppressive
      phenotypes have been observed in patient samples and the EMU-TCL1 mouse model of
      CLL. Myeloid cells were thereby shown to enhance survival of CLL cells and
      contribute to apoptosis-resistance, to suppress anti-tumoral immunity, and to be
      involved in immune deficiency of leukemia patients. In addition, treatment
      regimens that are currently used for CLL target not only directly the malignant
      cells, but have also an impact on non-malignant bystander cells, including
      myeloid cells. This review summarizes current literature on these aspects and
      gives a perspective on how our current knowledge might be used to design novel
      immunotherapeutic approaches that can be combined with CLL-targeting drugs to
      achieve better therapeutic responses in CLL patients.

PMID- 29173972
TI  - [Mechanisms of resistance of cancer stem cells to chemotherapy].

PMID- 29173973
TI  - [Allogeneic haematopoietic cell transplantation for indolent lymphomas:
      Guidelines from the Francophone Society Bone Marrow Transplantation and Cellular
      Therapy (SFGM-TC)].
AB  - Despite great improvements in the outcome of patients with lymphoma, some may
      still relapse or present with primary refractory disease. In these situations,
      allogeneic hematopoietic cell transplantation is a potentially curative option,
      this is true particularly the case of relapse after autologous stem cell
      transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have
      started to challenge the use of allogeneic hematopoietic cell transplantation for
      relapsed or refractory lymphoma. During the 2016 annual workshop of the
      Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM
      TC), we performed a comprehensive review of the literature published in the last
      10 years and established guidelines to clarify the indications and transplant
      modalities in this setting. This paper specifically reports on our conclusions
      regarding indolent lymphomas, mainly follicular lymphoma and chronic lymphocytic
      leukemia.

PMID- 29173974
TI  - [Indications and follow-up for autologous hematopoietic stem cell transplantation
      in autoimmune and autoinflammatory diseases: Guidelines from the Francophone
      Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].
AB  - The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM
      TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical
      practices harmonization workshop series in September 2017 in Lille, France and
      updated recommendations for indications and follow-up in autologous hematopoietic
      stem cell transplantation in autoimmune and autoinflammatory diseases, previously
      published under the auspices of SFGM-TC.

PMID- 29173975
TI  - [Non eligibility criteria for hematopoietic stem cell donors: Guidelines from the
      Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM
      TC)].
AB  - The evolution of HLA typing and transplantation techniques makes it easier to
      identify a donor for hematopoietic stem cell (HSC) transplantation. This
      activity, strongly regulated by regulatory or normative texts, implies in
      addition biological, medical, para-medical and sometimes psychological
      evaluations. The benefit/risk discussion is complicated because it must take into
      account the benefit/risk ratio for the recipient, and the donor risk. No Evidence
      Based Medicine data is available and serious events are very rare situations.
      Biovigilance declarations and their analysis are of fundamental importance.
      Certain obvious and definite contraindications could be detected very early in
      the process. It is important to assess whether a risk factor or pathology
      contributes to increasing the risk associated with collection. In case of
      recipient risk, the situation should be discussed with the patient team. These
      recommendations focus on adult peripheral blood HSC donors. They refer to donor
      information, confidentiality of exchanges, the impact of moral or material
      pressures, declarations of biovigilance, collegiality and traceability of
      difficult decisions, desirable experience and training for doctors in charge, use
      of expert advice informed by an explicit exchange on the possible risks,
      parsimony of therapeutic interventions and minimization of risks for the donor.
      We also recommend creation, availability and use by the community of tools and
      documents (registries, questionnaires, synthetic recommendations, feedback, and
      collegial qualification meetings) useful for practice.

PMID- 29173976
TI  - Phase 2 Study of Weekly Paclitaxel Plus Estramustine in Metastatic Hormone
      Refractory Prostate Carcinoma: ECOG-ACRIN Cancer Research Group (E1898) Trial.
AB  - INTRODUCTION: This multicenter phase 2 study assessed the combination of
      estramustine and weekly paclitaxel with metastatic castration-resistant prostate
      cancer (CRPC). PATIENTS AND METHODS: We enrolled 77 patients who had received no
      prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were
      eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided
      intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral
      estramustine 280 mg twice daily for 3 days beginning 24 hours before the first
      dose of paclitaxel. The primary end point was rate of objective or prostate
      specific antigen (PSA) response at 16 weeks. A 50% response rate was considered
      of further interest. RESULTS: Eligible patients received a median of 3 cycles
      (range, 1-10 cycles). The response rate among patients with measurable disease
      was 34% (95% confidence interval [CI], 19-52). The PSA response rate was 58% (95%
      CI, 47-70). Clinical benefit rate was 45% (95% CI, 33-57). The median progression
      free survival was 5.9 months (95% CI, 4.4-6.7). The median overall survival was
      17.6 months (95% CI, 14.6-20.8). The most common clinical grade 3/4 toxicities
      were fatigue (14%) and sensory neuropathy (7%). Grade 3/4 hematologic toxicities
      included lymphopenia (21%) and anemia (9%). There was one toxicity-related death.
      Quality-of-life scores improved by week 8, but the change was not statistically
      significant. CONCLUSION: The combination has activity defined by PSA declines in
      CRPC but did not meet the protocol-specified end point for efficacy as defined by
      objective response rate. Since this study was conducted, more effective, better
      tolerated regimens have been developed.

PMID- 29173977
TI  - [European guidelines (ESMO-ESGO-ESTRO consensus conference) for the management of
      endometrial cancer].
AB  - Endometrial cancer (EC) is a major source of morbidity and mortality in women
      worldwide. In France, in 2015, EC was the first gynecological cancer in terms of
      incidence. Its prognosis is considered favorable because it is most often limited
      to the uterus at diagnosis. Nevertheless, it is a heterogeneous pathology and 5
      year overall survival can vary from 92 % to 42 % in FIGO stage I depending on its
      histological characteristics. This great heterogeneity leads to important
      disparities in its surgical management as well as in indications for adjuvant
      therapies. A consensus conference including three different European learned
      societies (ESMO-ESGO-ESTRO) has recently established new recommendations in order
      to standardize its management. One of the main points is the emergence of a new
      subgroup of patients at risk of recurrence (high-intermediate risk group).
      Concerning nodal staging, indications are still somewhat blurred for intermediate
      and high-intermediate risk groups. The sentinel lymph node biopsy remains an
      experimental procedure in contrast with American guidelines. Concerning adjuvant
      therapies, the place of chemotherapy and its combination with external beam
      radiotherapy should be explored, especially for patients with high risk EC and
      for certain histological subtypes.

PMID- 29173978
TI  - [Allogeneic hematopoietic cell transplantation for Hodgkin's disease, mantle cell
      lymphoma and other rare entities: Guidelines from the Francophone Society of Bone
      Marrow Transplantation and Cellular Therapy (SFGM-TC)].
AB  - Despite great improvements in the outcome of patients with lymphoma, some may
      still relapse or present with primary refractory disease. In these situations,
      allogeneic haematopoietic cell transplantation is a potentially curative option,
      in particular in the case of relapse after autologous stem cell transplantation.
      Recently, novel agents such as anti-PD1 and BTK inhibitors have started to
      challenge the use of allogeneic haematopoietic cell transplantation for relapsed
      or refractory lymphoma. During the 2016 annual workshop of the Francophone
      Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we
      performed a comprehensive review of the literature published in the last 10 years
      and established guidelines to clarify the indications and transplant modalities
      in this setting. This manuscript specifically reports on our conclusions
      regarding Hodgkin's lymphoma as well as rarer entities, such as T cell lymphomas.

PMID- 29173979
TI  - [Dose adaptation of the drugs used for hematopoietic stem-cell transplantation in
      patients with comorbidity: Obesity, chronic renal disease or hepatopathy:
      Guidelines from the Francophone Society of Bone Marrow Transplantation and
      Cellular Therapy (SFGM-TC)].
AB  - In September 2016 in Lille, France, the Francophone Society of Bone Marrow
      Transplantation and Cellular Therapy (SFGM-TC) organized the 7th Allogeneic Stem
      Cell Transplantation Clinical Practices Harmonization Workshop Series. Our work
      group focused on chemotherapy drug dose adaptation for hematopoietic stem cell
      transplantation patients presenting a comorbidity. The purpose of this workshop
      was to provide recommendations on chemotherapy drug dose adaptation for patient
      populations receiving hematopoietic stem cell transplantation who also had the
      following comorbidities: obesity, chronic kidney disease and hepatopathy.

PMID- 29173980
TI  - [Allogeneic haematopoietic cell transplantation for diffuse large B cell
      lymphoma: Guidelines from the Francophone Society of Bone Marrow Transplantation
      and Cellular Therapy (SFGM-TC)].
AB  - Despite great improvements in the outcome of patients with lymphoma, some may
      still relapse or present with primary refractory disease. In these situations,
      allogeneic hematopoietic cell transplantation is a potentially curative option,
      this is true particularly in the case of after autologous stem cell
      transplantation if remission can be achieved. Recently, novel agents such as anti
      PD1 and BTK inhibitors have started to challenge the use of allogeneic
      hematopoietic cell transplantation for relapsed or refractory lymphoma. During
      the 2016 annual workshop of the Francophone Society of Bone Marrow
      Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive
      review of the literature published in the last 10 years and established
      guidelines to clarify the indications and transplant modalities in this setting.
      This section specifically reports on our conclusions regarding diffuse large B
      cell lymphoma.

PMID- 29173982
TI  - Silencing of CEMIP suppresses Wnt/beta-catenin/Snail signaling transduction and
      inhibits EMT program of colorectal cancer cells.
AB  - Cell migration inducing hyaluronan binding protein (CEMIP) is a hyaluronic acid
      binding protein, the abnormal elevation of which is suggested as a contributor in
      the carcinogenesis of colorectal cancer (CRC). Cancer cells lose their adhesive
      properties and acquire an enhanced mobility by undergoing epithelial-mesenchymal
      transition (EMT). This study is performed to investigate whether and how CEMIP
      orchestrates the EMT process of CRC cells. To avoid the unexpected off-target
      effects possibly caused by one single shRNA, two shRNAs targeting different mRNA
      regions of CEMIP gene were used to knock down the mRNA and protein expression of
      CEMIP. Our data showed that the proliferation, migration and invasion of two CRC
      cell lines, HCT116 and SW480 cells, were inhibited by CEMIP shRNA. We here
      defined EMT as the complete or partial loss of E-cadherin and zona occludens
      protein 1 (ZO-1) (epithelial markers) and the gain of Vimentin and N-cadherin
      (mesenchymal markers), and found that the EMT process was attenuated in CEMIP
      silenced SW480 cells. Snail, a direct target of beta-catenin/T cell factor
      complex, is known to activate the EMT program during cancer metastasis. CEMIP
      shRNA was further found to suppress the Wnt/beta-catenin/Snail signaling
      transduction in CRC cells as manifested by the decreased nuclear beta-catenin and
      Snail. Collectively, our work demonstrates that CEMIP contributes to metastatic
      phenotype of CRC cells in vitro.

PMID- 29173983
TI  - [How to explain glomerular filtration rate decrease in intra-abdominal
      hypertension?]
AB  - Intra-abdominal hypertension (IAH) is a frequent and serious condition affecting
      critical care patients. IAH diagnostic needs intravesical pressure (IVP)
      measurement which is recommended for monitoring patients presenting IAH risk
      factors. IVP monitoring is probably insufficient in daily practice. This could be
      explained by lack of knowledge about IAH physiopathology, which leads to absence
      of therapeutic target. Acute kidney injury (AKI) is the earliest and most
      described organ dysfunction associated with IAH. Moreover, AKI gravity seems to
      correlates with IAH severity. Physiopathological aspects explaining glomerular
      filtration rate (GFR) decrease with IAH are probably multifactorial and not
      completely understood. The role of renal venous congestion is essential to
      explain AKI in IAH. GFR decrease may reflect a "glomerular capillary shunt" due
      to a decrease of renal plasmatic flow. Monitoring IVP in daily practice in
      patients presenting risk factors of IAH would improve knowledge about this
      condition and the associated AKI.

PMID- 29173984
TI  - Black spot or "tache noire" in mediterranean spotted fever.

PMID- 29173981
TI  - Glucocerebrosidase haploinsufficiency in A53T alpha-synuclein mice impacts
      disease onset and course.
AB  - Mutations in GBA1 encountered in Gaucher disease are a leading risk factor for
      Parkinson disease and associated Lewy body disorders. Many GBA1 mutation
      carriers, especially those with severe or null GBA1 alleles, have earlier and
      more progressive parkinsonism. To model the effect of partial glucocerebrosidase
      deficiency on neurological progression in vivo, mice with a human A53T alpha
      synuclein (SNCAA53T) transgene were crossed with heterozygous null gba mice
      (gba+/-). Survival analysis of 84 mice showed that in gba+/-//SNCAA53T
      hemizygotes and homozygotes, the symptom onset was significantly earlier than in
      gba+/+//SNCAA53T mice (p-values 0.023-0.0030), with exacerbated disease
      progression (p-value <0.0001). Over-expression of SNCAA53T had no effect on
      glucocerebrosidase levels or activity. Immunoblotting demonstrated that gba
      haploinsufficiency did not lead to increased levels of either monomeric SNCA or
      insoluble high molecular weight SNCA in this model. Immunohistochemical analyses
      demonstrated that the abundance and distribution of SNCA pathology was also
      unaltered by gba haploinsufficiency. Thus, while the underlying mechanism is not
      clear, this model shows that gba deficiency impacts the age of onset and disease
      duration in aged SNCAA53T mice, providing a valuable resource to identify
      modifiers, pathways and possible moonlighting roles of glucocerebrosidase in
      Parkinson pathogenesis.

PMID- 29173985
TI  - Effects of a resistance training program on balance and fatigue perception in
      patients with Parkinson's disease: A randomized controlled trial.
AB  - INTRODUCTION AND OBJECTIVE: Fatigue and balance impairment leads to a loss of
      independence and are important to adequately manage. The objective of this study
      was to examine the effects of a resistance training program on dynamic balance
      and fatigue in patients with Parkinson's disease (PD). PATIENTS AND METHODS:
      Randomized controlled trial. Forty-six patients with PD were randomly allocated
      to an intervention group receiving a 8-week resistance training program focused
      on lower limbs or to a control group. Balance was assessed using the Mini-BESTest
      and fatigue was assessed by the Piper Fatigue Scale. RESULTS: Patients in the
      intervention group improved significantly (p<0.05) on dynamic balance (reactive
      postural control and total values) and perceived fatigue. CONCLUSIONS: An 8-week
      resistance training program was found to be effective at improving dynamic
      balance and fatigue in patients with PD.

PMID- 29173986
TI  - Contributions about the use of intravenous iron.

PMID- 29173987
TI  - Epidemiological, clinical, microbiological and therapeutic differences in
      tuberculosis disease in patients with and without HIV infection.
AB  - BACKGROUND AND OBJECTIVE: Our objective is to analyze the incidence of
      tuberculosis (TB) in our population and to compare the characteristics of
      patients with and without HIV infection. PATIENTS AND METHODS: Clinical
      epidemiological retrospective cohort study that included patients diagnosed with
      TB with and without HIV infection between 2005-2016 in the province of
      Guadalajara (Spain). Epidemiological, clinical, microbiological and therapeutic
      variables were assessed, including microbiological resistances. RESULTS: TB was
      diagnosed in 261 patients. There were 25 patients (9.6%) who had HIV infection.
      Patients with HIV infection were predominantly males, had higher incidence of
      hepatitis C virus, a higher percentage of extrapulmonary TB, a higher prevalence
      of resistance to isoniazid and rifampicin, a greater paradoxical response and a
      longer average hospital stay. On the other hand, they had a lower percentage of
      positive tuberculin skin test and positive sputum smear (microscopy). A
      significant percentage of TB patients had no serology for HIV. CONCLUSION:
      Patients with HIV infection show remarkable differences in epidemiological,
      clinical and resistance variables to antituberculosis drugs. A high percentage of
      patients with TB were not tested for HIV.

PMID- 29173988
TI  - Non compaction cardiomyopathy: Review of a controversial entity.
AB  - Non-compaction cardiomyopathy is a heterogeneous and complex entity concerning
      which there are still many doubts to be resolved. While the American Heart
      Association includes it among genetic cardiomyopathies, the European Society of
      Cardiology treats it as an unclassified cardiomyopathy. It may present in a
      sporadic or familial form, isolated or associated with other heart diseases,
      affecting only the left ventricle or both and can sometimes appear as a mixed
      phenotype in patients with other cardiomyopathies. Different forms of clinical
      presentation are also associated with its different morphological manifestations,
      and even non-compaction of the left ventricle may be triggered by other
      physiological or pathological processes. The purpose of this review is an update
      of this entity and its controversies.

PMID- 29173989
TI  - Use of Monte Carlo Techniques in Nuclear Medicine.

PMID- 29173990
TI  - Reimbursement Anxiety Disorder.

PMID- 29173991
TI  - Practicing Radiology During a Hurricane.

PMID- 29173992
TI  - Good, Better, Better Still . . .

PMID- 29173993
TI  - Letter to the Editor: Regarding Foster et al., Neonatal C57BL/6J and parkin mice
      respond differently following developmental manganese exposure: Result of a high
      dose pilot study.

PMID- 29173994
TI  - Neurotoxicity of carbon monoxide targets caudate-mediated dopaminergic system.
AB  - The clinical features of parkinsonism in carbon monoxide (CO) intoxication have
      been associated with striatal-related neuronal networks. As parkinsonian and
      neuropsychiatric features are both related to presynaptic dopaminergic integrity,
      the aim of this study was to explore the clinical significance of 99mTcTRODAT-1
      in grading neurobehavioral scores and parkinsonian severity in CO intoxication.
      We enrolled 64 patients with CO intoxication, including 29 with parkinsonism
      (parkinsonism[+] group) and 35 without (parkinsonism[-] group). All of the
      patients received 99mTcTRODAT-1 neuroimaging evaluations, comprehensive
      neurobehavioral tests and assessments of the severity of parkinsonism using
      Unified Parkinson's Disease Rating Scale (UPDRS)-part III motor score. Univariate
      and multivariate regression analyses were used to test the predictive factors and
      scores for a diagnosis of parkinsonism and its severity. The parkinsonism(+)
      group had significantly lower cognitive scores and higher neuropsychiatric total
      scores compared with the parkinsonism(-) group, both of which were independently
      related to the severity of parkinsonism. 99mTcTRODAT-1 regional caudate signals
      were correlated with tremors at rest, action or postural tremors of the hands,
      bradykinesia and hypokinesia, and visuospatial, verbal fluency, abstract thinking
      and digit backwards scores. Scores of the neurobehavioral tests and UPDRS items
      were highly correlated (p<0.01). Our results validated the initial hypothesis in
      that neurobehavioral deficits and parkinsonian symptoms were highly related. This
      association was independent of demographic factors and initial carboxyhemoglobin
      level. Within the presynaptic dopaminergic circuit, the clinical role of the
      caudate in mediating the clinical symptoms in CO intoxication may outweigh the
      putamen.

PMID- 29173995
TI  - Reflectance Confocal Microscopy: A Promising Tool to Identify Malignancy in
      Melanocytic Lesions Exhibiting a Dermoscopic Island.
AB  - The dermoscopic island is described as a well-defined area in a melanocytic
      lesion, with a different dermoscopic pattern from the rest of the lesion. It is
      predictive of melanoma, particularly when the pattern of the island is atypical.
      We present the reflectance confocal microscopy (RCM) findings in 3 lesions with
      dermoscopic islands: nevus-associated melanoma, melanocytic nevus, and in situ
      melanoma. The nevus-associated melanoma and in situ melanoma presented cellular
      atypia (atypical cells in isolation or forming nests) and architectural
      distortion on RCM. The nevus presented a dermoscopic island with a typical
      globular pattern with dense nests and no atypia on RCM. Dermoscopic island is
      mainly associated with in situ and nevus-associated melanomas. RCM offers good
      cellular resolution to the depth of the reticular dermis and is useful for
      diagnosing of melanomas presenting a dermoscopic island.

PMID- 29173996
TI  - Ulcerated Penile Lesion.

PMID- 29173997
TI  - The impact of different torques for the insertion of immediately loaded implants
      on the peri-implant levels of angiogenesis- and bone-related markers.
AB  - The aim of this split-mouth, randomized, double-blind, controlled clinical trial
      was to evaluate the influence of different insertion torque values for dental
      implants on bone- and angiogenesis-related marker profiles. Eighteen edentulous
      patients received dental implants and fixed complete-arch mandibular prostheses.
      The implants (n=36) were assigned randomly to two groups: reduced torque (n=18),
      with insertion torque <30Ncm; and conventional torque (n=18), with insertion
      torque >=30Ncm. Levels of vascular endothelial growth factor (VEGF), placental
      growth factor, bone morphogenetic protein 9 (BMP-9), periostin, osteoprotegerin
      (OPG), and tartrate-resistant acid phosphatase (TRAP) in the peri-implant fluid
      were quantified at 7, 14, 30, and 120days after implant placement. Inter-group
      comparisons showed that VEGF and OPG levels were higher in the low-level torque
      group than in the conventional torque group on days 7 and 30, respectively
      (P<0.05). BMP-9 and periostin levels were higher in the conventional group than
      in the low-level torque group on day 120, and TRAP was up-regulated around
      implants inserted with conventional torque when compared to those inserted with
      lower-level torque at all time points evaluated (P<0.05). In conclusion, the use
      of different levels of torque for implantation of immediately loaded implants
      significantly influenced the levels of bone- and angiogenesis-related markers
      during early peri-implant repair.

PMID- 29173998
TI  - [Rehabilitation in elderly frail patients with acute heart failure. Training in
      REHAB-HF Pilot Study].

PMID- 29173999
TI  - Chocolate intake in pre-menopausal women.

PMID- 29174000
TI  - Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic
      circuits and causes body weight increase.
AB  - OBJECTIVE: Leptin is a cytokine produced by adipose tissue that acts mainly on
      the hypothalamus to regulate appetite and energy homeostasis. Previous studies
      revealed that the leptin receptor is expressed not only in neurons, but also in
      glial cells. Microglia are resident immune cells in the brain that play an
      essential role in immune defense and neural network development. Previously we
      reported that microglial morphology and cytokine production are changed in the
      leptin receptor deficient db/db mouse, suggesting that leptin's central effects
      on metabolic control might involve signaling through microglia. In the current
      study, we aimed to uncover the role of leptin signaling in microglia in systemic
      metabolic control. METHODS: We generated a mouse model with leptin receptor
      deficiency, specifically in the myeloid cells, to determine the role of
      microglial leptin signaling in the development of metabolic disease and to
      investigate microglial functions. RESULTS: We discovered that these mice have
      increased body weight with hyperphagia. In the hypothalamus, pro-opiomelanocortin
      neuron numbers in the arcuate nucleus (ARC) and alpha-MSH projections from the
      ARC to the paraventricular nucleus (PVN) decreased, which was accompanied by the
      presence of less ramified microglia with impaired phagocytic capacity in the PVN.
      CONCLUSIONS: Myeloid cell leptin receptor deficient mice partially replicate the
      db/db phenotype. Leptin signaling in hypothalamic microglia is important for
      microglial function and a correct formation of the hypothalamic neuronal circuit
      regulating metabolism.

PMID- 29174001
TI  - Hot spots for the protein engineering of Baeyer-Villiger monooxygenases.
AB  - Baeyer-Villiger monooxygenases (BVMOs) are versatile biocatalysts for the
      conversion of ketones to lactones or esters while also being able to efficiently
      oxidize sulfides to sulfoxides. However, there are limitations for the
      application of BVMOs in synthesis. In this review we provide an overview of the
      protein engineering studies aiming at optimizing different properties of BVMOs.
      We describe hot spots in the active sites of certain BVMOs that have been
      successfully targeted for changing the substrate scope, as well as the
      possibility to influence this property by allosteric effects. The identified hot
      spots in the active sites for controlling enantio- and regioselectivity are shown
      to be transferable to other BVMOs and we describe concepts to influence
      heteroatom oxidation, improve protein stability and change the cofactor
      dependency of BVMOs. Summarizing all these different studies enabled the
      identification of BVMO- or property-dependent as well as universal hot spots.

PMID- 29174002
TI  - Small-diameter compression screws completely embedded in bone for rigid internal
      fixation of the condylar head of the mandible.

PMID- 29174003
TI  - Response to Correspondence on "A Better Understanding of Brain Involvement in
      22q11.2 Deletion Syndrome".

PMID- 29174004
TI  - Chasing Zebras: A Child with Skin Stripes and Whorls.

PMID- 29174005
TI  - Quick Brain Magnetic Resonance Imaging With Diffusion-Weighted Imaging as a First
      Imaging Modality in Pediatric Stroke.
AB  - BACKGROUND: Diagnostic delay hinders management of pediatric arterial ischemic
      stroke. Quick brain MRI with diffusion-weighted imaging sequences may provide a
      rapid diagnosis without the ionizing radiation of a computed tomography (CT)
      scan. METHODS: This was a single center retrospective chart review of children
      one month to 18 years old with acute arterial ischemic stroke hospitalized
      between January 2010 and January 2017. We evaluated sensitivity and the time to
      diagnostic study based on the first imaging study (CT or quick brain MRI with
      diffusion-weighted imaging). RESULTS: Twenty-five patients were included. Eleven
      patients (44%) were initially assessed with CT, 10 (40%) with quick brain MRI
      with diffusion-weighted imaging, and four (16%) with a full MRI. Compared with
      children undergoing CT, children with quick brain MRI with diffusion-weighted
      imaging as first study were younger (5.8 versus 14.1 years, P < 0.001) and were
      more likely to be hospitalized at stroke onset (70% versus 18.2%, P = 0.03).
      Quick brain MRI with diffusion-weighted imaging was more sensitive for ischemia
      than CT (100% versus 27.3%). The median time from presentation to diagnostic
      imaging was 4.3 hours, with no differences between CT and quick brain MRI with
      diffusion-weighted imaging groups, although the quick brain MRI with diffusion
      weighted imaging group had a shorter median time from first imaging to diagnostic
      imaging (P = 0.002). There were no significant missed findings on quick brain MRI
      with diffusion-weighted imaging. CONCLUSIONS: Quick brain MRI with diffusion
      weighted imaging was more sensitive than CT for detecting ischemia and may be
      considered as the first study for some children presenting with suspected
      arterial ischemic stroke.

PMID- 29174006
TI  - Premature Termination of Treatment in Neonatal Herpes Simplex Virus Encephalitis.

PMID- 29174007
TI  - [Acute hemorrhagic edema of infancy associated with Coxsackie virus infection].
AB  - Acute hemorrhagic edema of infancy is a rare but benign vasculitis occurring in
      infants aged from 4 to 24 months. Skin lesions can take various forms, including
      extensive hemorrhagic purpura, and can therefore be mistaken for purpura
      fulminans if associated with fever, which leads to initiating broad-spectrum
      antibiotic treatment. In the present case, we describe a 7-month-old boy with
      acute hemorrhagic edema of infancy and rapidly extensive purpura lesions that led
      to intravenous cefotaxime and amikacin treatment. Diagnosis was made on the next
      day by a dermatologist, based on the typical aspect of skin lesions, hemodynamic
      stability, and negative bacteriological samples. Coxsackie virus B5, a pathogenic
      enterovirus, was found by specific PCR in cerebrospinal fluid. The outcome was
      spontaneously favorable after discontinuation of antibiotics on day 2. We discuss
      the imputability of the enterovirus in triggering this case of acute hemorrhagic
      edema of infancy.

PMID- 29174008
TI  - [The use of the Debriefing Assessment for Simulation in Healthcare (DASH) in a
      simulation-based team learning program for newborn resuscitation in the delivery
      room].
AB  - OBJECTIVE: To evaluate the contribution of the Debriefing Assessment for
      Simulation in Healthcare (DASH, Centre for Medical Simulation, Harvard) in a high
      fidelity simulation in situ program used for newborn resuscitation training.
      METHODS: The DASH was scored by trainees and instructors at the end of the
      session. The instructors' feedback and opinions were collected. RESULTS: The
      study included 16 training sessions (ten maternity units) with 156 trainees and
      ten instructors (45 DASH). The mean DASH score was rated at 6.6/7 by the learners
      and 5.4/7 by the instructors. For each element, the instructors scored the DASH
      lower than the learners (P<0.001). For each session, the instructors' DASH scores
      were lower than the learners' score (P<0.001). The instructors' DASH scores
      progressed during the first three sessions of the study. The instructors
      evaluated the DASH's usefulness at 3.6/7 in self-evaluation and at 6.3/7 if used
      collectively. CONCLUSION: The trainees evaluated the debriefing with high-level
      DASH scores, thus validating the educational aim of the program. In contrast, the
      instructors' DASH scores were lower and heterogeneous. Debriefing high-fidelity
      simulations remains a complex exercise. The use of the DASH can be a helpful
      measure for instructors in regard of their own practice. Its main advantage could
      be in providing a validated tool that will allow a "debriefing of debriefing".

PMID- 29174009
TI  - Guidelines for the clinical management and follow-up of infants with inconclusive
      cystic fibrosis diagnosis through newborn screening.
AB  - Neonatal screening for cystic fibrosis (CF) can detect infants with elevated
      immunoreactive trypsinogen (IRT) levels and inconclusive sweat tests and/or CFTR
      DNA results. These cases of uncertain diagnosis are defined by (1) either the
      presence of at most one CF-associated cystic fibrosis transmembrane conductance
      regulator (CFTR) mutation with sweat chloride values between 30 and 59mmol/L or
      (2) two CFTR mutations with at least one of unknown pathogenic potential and a
      sweat chloride concentration below 60mmol/L. This encompasses various clinical
      situations whose progression cannot be predicted. In these cases, a sweat
      chloride test has to be repeated at 12 months, and if possible at 6 and 24 months
      of life along with extended CFTR sequencing to detect rare mutations. When the
      diagnosis is not definite, CFTR functional explorations may provide a better
      understanding of CFTR dysfunction. The initial evaluation of these infants must
      be conducted in dedicated CF reference centers and should include bacteriological
      sputum analysis, chest radiology, and fecal elastase assay. The primary care
      physicians in charge of these patients should be familiar with the current
      management of CF and should work in collaboration with CF centers. A follow-up
      should be performed in a CF reference center at 3, 6, and 12 months of life and
      every year thereafter. Any symptom indicative of CF requires immediate
      reevaluation of the diagnosis. These guidelines were established by the "neonatal
      screening and difficult diagnoses" working group of the French CF society. Their
      objective is to standardize the management of infants with unclear diagnosis.

PMID- 29174010
TI  - Evaluation of photosynthetic activities in thylakoid membranes by means of
      Fourier transform infrared spectroscopy.
AB  - Light-induced Fourier transformed infrared (FTIR) difference spectroscopy is a
      powerful method to study the structures and reactions of redox cofactors involved
      in the photosynthetic electron transport chain. So far, most of the FTIR studies
      of the reactions of oxygenic photosynthesis have been performed using isolated
      photosystem I (PSI) and photosystem II (PSII) preparations, which, however, could
      be modified during isolation procedures. In this study, we developed a
      methodology to evaluate the photosynthetic activities of thylakoids using FTIR
      spectroscopy. FTIR difference spectra upon successive flashes using thylakoids
      from spinach exhibited signals typical of the S-state cycle at the Mn4CaO5
      cluster and QB reactions in PSII with period-four and -two oscillations,
      respectively. Similar measurement in the presence of an artificial quinone as an
      exogenous electron acceptor showed features specific to the S-state cycle.
      Simulations of the oscillation patterns provided the quantum efficiencies of the
      S-state cycle and electron transfer in PSII. Moreover, FTIR measurement under
      continuous illumination on thylakoids in the presence of DCMU showed signals due
      to QA reduction and P700 oxidation simultaneously. From the relative amplitudes
      of marker bands of QA- and P700+, the molar ratio of photoactive PSII and PSI
      centers in thylakoids was estimated. FTIR analyses of the photo-reactions in
      thylakoids, which are more intact than isolated photosystems, will be useful in
      investigations of the photosynthetic mechanism especially by genetic modification
      of photosystem proteins.

PMID- 29174011
TI  - Apoprotein heterogeneity increases spectral disorder and a step-wise modification
      of the B850 fluorescence peak position.
AB  - It has already been established that the quaternary structure of the main light
      harvesting complex (LH2) from the photosynthetic bacterium Rhodopseudomonas
      palustris is a nonameric 'ring' of PucAB heterodimers and under low-light
      culturing conditions an increased diversity of PucB synthesis occurs. In this
      work, single molecule fluorescence emission studies show that different classes
      of LH2 'rings' are present in "low-light" adapted cells and that an unknown
      chaperon process creates multiple sub-types of 'rings' with more conformational
      sub-states and configurations. This increase in spectral disorder significantly
      augments the cross-section for photon absorption and subsequent energy flow to
      the reaction centre trap when photon availability is a limiting factor. This work
      highlights yet another variant used by phototrophs to gather energy for cellular
      development.

PMID- 29174012
TI  - Peripapillary and Macular Vessel Density in Patients with Primary Open-Angle
      Glaucoma and Unilateral Visual Field Loss.
AB  - PURPOSE: To characterize OCT angiography (OCT-A) vessel density of patients with
      primary open-angle glaucoma (POAG) with unilateral visual field (VF) loss.
      DESIGN: Cross-sectional study. PARTICIPANTS: A total of 33 patients with POAG
      with a VF defect in 1 eye (mean VF mean deviation [MD], -3.9+/-3.1 decibels [dB])
      and normal VF in the other eye (mean VF MD, -0.2+/-0.9 dB) and 33 healthy eyes.
      METHODS: All subjects underwent OCT-A imaging, spectral-domain (SD)-OCT imaging,
      and VF testing. OCT-A retinal vascular measurements were summarized as whole
      image vessel density (wiVD), circumpapillary vessel density (cpVD), and
      parafoveal vessel density (pfVD). Inter-eye differences in vascular measures, as
      well as SD OCT retinal nerve fiber layer (RNFL), macular ganglion cell complex
      (mGCC) thickness, and rim area measurements in glaucoma and healthy eyes were
      compared. Areas under the receiver operating characteristic curves (AUROCs) were
      used to evaluate diagnostic accuracy for differentiating between unaffected eyes
      of patients with POAG and healthy eyes. MAIN OUTCOME MEASURES: Difference in OCT
      A vessel density and SD OCT structural parameters between unaffected eyes of
      patients with POAG with the fellow affected eyes and healthy controls. RESULTS:
      Mean wiVD in unaffected eyes of patients with POAG (52.0%) was higher than in
      their fellow affected eyes (48.8%) but lower than in healthy eyes (55.9%; P <
      0.001). Mean circumpapillary RNFL (cpRNFL) thickness, mGCC thickness, and rim
      area measurement in unaffected eyes of patients with POAG (87.5 MUm, 87.7 MUm,
      and 1.0 mm2) were also higher than those measurements in their fellow eyes (76.5
      MUm, 79.5 MUm, and 0.8 mm2; P < 0.001) and lower than in healthy eyes (98.0 MUm,
      94.5 MUm, and 1.4 mm2; P < 0.001). The AUROCs for differentiating unaffected eyes
      of patients with POAG from healthy eyes were highest for wiVD (0.84), followed by
      mGCC (0.78), cpRNFL (0.77), and pfVD (0.69). CONCLUSIONS: OCT-A measures detect
      changes in retinal microvasculature before VF damage is detectable in patients
      with POAG, and these changes may reflect damage to tissues relevant to the
      pathophysiology of glaucoma. Longitudinal studies are needed to determine whether
      OCT-A measures can improve the detection or prediction of the onset and
      progression of glaucoma.

PMID- 29174013
TI  - The minor histocompatibility antigen 1 (HMHA1)/ArhGAP45 is a RacGAP and a novel
      regulator of endothelial integrity.
AB  - Endothelial cells line the vasculature and act as gatekeepers that control the
      passage of plasma, macromolecules and cells from the circulation to the
      interstitial space. Dysfunction of the endothelial barrier can lead to
      uncontrolled leak or edema. Vascular leakage is a hallmark of a range of diseases
      and despite its large impact no specialized therapies are available to prevent or
      reduce it. RhoGTPases are known key regulators of cellular behavior that are
      directly involved in the regulation of the endothelial barrier. We recently
      performed a comprehensive analysis of the effect of all RhoGTPases and their
      regulators on basal endothelial integrity. In addition to novel positive
      regulators of endothelial barrier function, we also identified novel negative
      regulators, of which the ArhGAP45 (also known as HMHA1) was the most significant.
      We now demonstrate that ArhGAP45 acts as a Rac-GAP (GTPase-Activating Protein) in
      endothelial cells, which explains its negative effect on endothelial barrier
      function. Silencing ArhGAP45 not only promotes basal endothelial barrier
      function, but also increases cellular surface area and induces sprout formation
      in a 3D-fibrin matrix. Our data further shows that loss of ArhGAP45 promotes
      migration and shear stress adaptation. In conclusion, we identify ArhGAP45
      (HMHA1) as a novel regulator, which contributes to the fine-tuning of the
      regulation of basal endothelial integrity.

PMID- 29174014
TI  - Nanotechnology and primary hemostasis: Differential effects of nanoparticles on
      platelet responses.
AB  - Despite the numerous advantages offered by diverse platforms based on
      nanomedicine, several nanomaterials have shown significant cell toxicity that
      could induce chronic adverse effects on human health. Blood compatibility is one
      of the leading factors to consider for the design and development of nanosystems
      as therapeutics. Aforementioned is because systemic circulation is the gateway
      for most nano-drug therapeutic systems and its interactions with the blood
      components such as platelets could influence the maintenance of hemostasis and
      thrombus formation. Unfortunately, the thrombotoxicity of some nanomaterials
      regarding the activation/inhibition of platelets limits their biomedical
      applications. Additionally, the critical factors that drive those effects on
      platelet function are still not entirely elucidated. In this work, we describe
      the effect of different nanomaterials on the platelet function, its action
      mechanisms, and future potential as nanotherapeutics.

PMID- 29174015
TI  - Effect of statin therapy on the prevention of new-onset acute coronary syndrome
      in patients with rheumatoid arthritis.
AB  - BACKGROUND: The aim of this study is to investigate whether statin therapy can
      reduce new-onset acute coronary syndrome (ACS) in patients with rheumatoid
      arthritis (RA). METHODS: We used a database from the Registry for Catastrophic
      Illness from the National Health Research Institute (NHRI) in Taiwan. All RA
      patients aged 18 or older, diagnosed between 1995 and 2013, without previous
      cardiovascular events were included. We divided participants into quartiles
      according to the accumulated statin equivalent dosage and tertiles of period of
      days of statin treatment to examine the possible dose-response effect. To avoid
      confounding effects, a 1:4 propensity score matching and Cox's proportional
      hazard regression models were applied to estimate the hazard ratios for ACS
      events in patients with and without statin use. RESULTS: Total 49,227 patients
      were included and PS matching identified 5483 patients receiving statins and
      21,932 who did not. RA patients treated with statins had lower incidence of first
      ACS event (IRR 0.779, 95% CI: 0.654-0.927, p=0.005) after PS matching. Statin
      therapy is associated with reduced risk of new ACS before PS matching (HR=0.847,
      95% CI: 0.737-0.973, p=0.019) and the beneficial effect is correlated with
      accumulated dose and therapy duration (HRs from Q1 to Q4 are 1.215, 0.825, 0.716
      and 0.611, p<0.001 for trend; HRs from T1 to T3 are 1.100, 0.841 and 0.611,
      p<0.001 for trend). These results remained robust after propensity matching.
      Comparison between 6 different statins, rosuvastatin seems to be associated with
      better outcome on ACS primary prevention after excluding participants taking more
      than one kind of statin. CONCLUSIONS: Our study demonstrated that statin therapy
      is associated with lower event rate of new-onset ACS in RA patients and the
      beneficial effect is dose-responsive.

PMID- 29174016
TI  - De novo mitral regurgitation as a cause of heart failure exacerbation in patients
      with hypertrophic cardiomyopathy.
AB  - AIMS: To determine the prevalence and mechanisms of de novo severe MR due to
      mitral valve structural abnormalities causing clinical deterioration in patients
      with HCM. METHODS AND RESULTS: This is an observational study based on HCM
      registry comprising consecutive HCM patients (n=397) who have been evaluated and
      followed in the Cardiomyopathy Clinic of Sheba Medical Center. Sixteen patients
      (4.0%), 8 males, mean age 65+/-14 years, developed acute clinical deterioration
      due to development of severe mitral regurgitation unrelated to mitral valve
      systolic anterior motion. Compared to the remaining HCM population, those
      patients were older at their initial diagnosis (51+/-20 vs. 38+/-18 years) and
      more often females. Most frequently (in 10 patients, 63%) mitral regurgitation
      resulted from a flail posterior leaflet, while 4 patients had severe prolapse and
      2 had isolated mitral annular/leaflet calcifications. Fourteen underwent surgery;
      myxomatous changes were found in all excised valves (n=9). On age-adjusted
      univariate analysis, 3 clinical parameters remained significantly associated with
      the development of de novo MR, female gender, LVOT obstruction and significant MR
      at baseline. On multivariable analysis, only LVOT obstruction (HR=3.8) and MR at
      baseline evaluation (HR=8.2) predicted development of severe MR. CONCLUSIONS: De
      novo severe MR leading to acute heart failure was repeatedly observed in our HCM
      series. This etiology needs to be considered as a cause of acute clinical
      deterioration in these patients.

PMID- 29174017
TI  - Additive and independent prognostic role of abnormal right ventricle and
      pulmonary hypertension in mitral-tricuspid surgery.
AB  - OBJECTIVE: To evaluate the additive and independent prognostic value of abnormal
      right ventricle (aRV) and pulmonary hypertension (PH) in patients undergoing
      mitral-tricuspid surgery. METHODS: From January 2009 to December 2012, 541
      patients underwent mitro-tricuspid surgery. The entire cohort was divided into 6
      subgroups: 63 cases had normal RV and no PH (Group A), 180 normal RV but moderate
      PH (Group B), 101 normal RV but severe PH (Group C), 15 abnormal RV and no-PH
      (Group D), 86 abnormal RV and moderate PH (Group E) and 96 abnormal RV and severe
      PH (Group F). RESULTS: Forty-two (7.8%) patients died in hospital due to any
      cause: 1.6% in group A, 3.9% in group B, 8.9% in group C, 13.3% in group D, 9.3%
      in group E, 15.6% in group E, p = 0.005. Among 78 patients with no-PH, mortality
      was significantly higher in patients with aRV (1.6%vs 13.3%. p = 0.03). Among 344
      patients with normal RV, mortality was significantly higher in patients with
      severe PH (1.6% vs 3.9% vs 8.9%. p = 0.03). Comparing the presence of both
      abnormal RV and severe PH with the remaining patients, mortality was
      significantly higher in the first group (15.6% 6.1%, p = 0.004). Multivariable
      analysis confirmed either the independent or the additive role of RV and PH.
      CONCLUSIONS: In patients undergoing mitral-tricuspid valve surgery, the presence
      of either RV dysfunction/dilatation or severe pulmonary hypertension, might play
      an independent prognostic role for mortality. The worst scenario is surely the
      contemporary presence of both conditions.

PMID- 29174018
TI  - Interobserver and intraobserver reliability of radiographic classification of
      acromioclavicular joint dislocations.
AB  - HYPOTHESIS AND BACKGROUND: The classification and treatment of acromioclavicular
      (AC) joint dislocations remain controversial. The purpose of this study was to
      determine the interobserver and intraobserver reliability of the Rockwood
      classification system. We hypothesized poor interobserver and intraobserver
      reliability, limiting the role of the Rockwood classification system in
      determining severity of AC joint dislocations and accurately guiding treatment
      decisions. METHODS: We identified 200 patients with AC joint injuries using the
      International Classification of Diseases, Ninth Revision code 831.04. Fifty
      patients met inclusion criteria. Deidentified radiographs were compiled and
      presented to 6 fellowship-trained upper extremity orthopedic surgeons. The
      surgeons classified each patient into 1 of the 6 classification types described
      by Rockwood. A second review was performed several months later by 2 surgeons. A
      kappa value was calculated to determine the interobserver and intraobserver
      reliability. RESULTS: The interobserver and intraobserver kappa values were fair
      (kappa = 0.278) and moderate (kappa = 0.468), respectively. Interobserver results
      showed that 4 of the 50 radiographic images had a unanimous classification.
      Intraobserver results for the 2 surgeons showed that 18 of the 50 images were
      rated the same on second review by the first surgeon and 38 of the 50 images were
      rated the same on second review by the second surgeon. CONCLUSION: We found that
      the Rockwood classification system has limited interobserver and intraobserver
      reliability. We believe that unreliable classification may account for some of
      the inconsistent treatment outcomes among patients with similarly classified
      injuries. We suggest that a better classification system is needed to use
      radiographic imaging for diagnosis and treatment of AC joint dislocations.

PMID- 29174019
TI  - Collar occupancy: A new quantitative imaging tool for morphometric analysis of
      oligodendrocytes.
AB  - BACKGROUND: Oligodendrocytes (OL) are the myelinating cells of the central
      nervous system. OL differentiation from oligodendrocyte progenitor cells (OPC) is
      accompanied by characteristic stereotypical morphological changes. Quantitative
      imaging of those morphological alterations during OPC differentiation is commonly
      used for characterization of new molecules in cell differentiation and
      myelination and screening of new pro-myelinating drugs. Current available imaging
      analysis methods imply a non-automated morphology assessment, which is time
      consuming and prone to user subjective evaluation. NEW METHOD: Here, we describe
      an automated high-throughput quantitative image analysis method entitled collar
      occupancy that allows morphometric ranking of different stages of in vitro OL
      differentiation in a high-content analysis format. Collar occupancy is based on
      the determination of the percentage of area occupied by OPC/OL cytoplasmic
      protrusions within a defined region that contains the protrusion network, the
      collar. RESULTS: We observed that more differentiated cells have higher collar
      occupancy and, therefore, this parameter correlates with the degree of OL
      differentiation. COMPARISON WITH EXISTING METHODS: In comparison with the method
      of manual categorization, we found the collar occupancy to be more robust and
      unbiased. Moreover, when coupled with myelin basic protein (MBP) staining to
      quantify the percentage of myelinating cells, we were able to evaluate the role
      of new molecules in OL differentiation and myelination, such as Dusp19 and Kank2.
      CONCLUSIONS: Altogether, we have successfully developed an automated and
      quantitative method to morphologically characterize OL differentiation in vitro
      that can be used in multiple studies of OL biology.

PMID- 29174020
TI  - Looking for Alzheimer's Disease morphometric signatures using machine learning
      techniques.
AB  - BACKGROUND: We present our results in the International challenge for automated
      prediction of MCI from MRI data. We evaluate the performance of MRI-based
      neuromorphometrics features (nMF) in the classification of Healthy Controls (HC),
      Mild Cognitive Impairment (MCI), converters MCI (cMCI) and Alzheimer's Disease
      (AD) patients. NEW METHODS: We propose to segregate participants in three groups
      according to Mini Mental State Examination score (MMSEs), searching for the main
      nMF in each group. Then we use them to develop a Multi Classifier System (MCS).
      We compare the MCS against a single classifier scheme using both MMSEs+nMF and
      nMF only. We repeat this comparison using three state-of-the-art classification
      algorithms. RESULTS: The MCS showed the best performance on both Accuracy and
      Area Under the Receiver Operating Curve (AUC) in comparison with single
      classifiers. The multiclass AUC for the MCS classification on Test Dataset were
      0.83 for HC, 0.76 for cMCI, 0.65 for MCI and 0.95 for AD. Furthermore, MCS's
      optimum accuracy on Neurodegenerative Disease (ND) detection (AD+cMCI vs MCI+HC)
      was 81.0% (AUC=0.88), while the single classifiers got 71.3% (AUC=0.86) and 63.1%
      (AUC=0.79) for MMSEs+nMF and only nMF respectively. COMPARISON WITH EXISTING
      METHOD: The proposed MCS showed a better performance than using all nMF into a
      single state-of-the-art classifier. CONCLUSIONS: These findings suggest that
      using cognitive scoring, e.g. MMSEs, in the design of a Multi Classifier System
      improves performance by allowing a better selection of MRI-based features.

PMID- 29174021
TI  - Sudden cardiac death preceded by ST segment elevations during ECG patch
      monitoring.
AB  - A 58-year-old male underwent ambulatory ECG monitoring with continuous patch
      monitoring (Zio XT Patch) for the complaint of episodic dyspnea. In the period of
      monitoring the patient suffered sudden cardiac death (SCD) with continuous ECG
      recording showing pronounced ST segment elevations followed by bradycardia and
      death. This report highlights the growing potential of continuous ST segment
      monitoring, and features the infrequent entity of ischemic electromechanical
      dissociation with bradyarrhythmia as a cause of SCD.

PMID- 29174022
TI  - Patients with left bundle branch block and left axis deviation show a specific
      left ventricular asynchrony pattern: Implications for left ventricular lead
      placement during CRT implantation.
AB  - BACKGROUND: Left bundle branch block (LBBB) and left axis deviation (LAD)
      patients may have poor response to resynchronization therapy (CRT). We sought to
      assess if LBBB and LAD patients show a specific pattern of mechanical asynchrony.
      METHODS: CRT candidates with non-ischemic cardiomyopathy and LBBB were
      categorized as having normal QRS axis (within -30 degrees  and +90 degrees ) or
      LAD (within -30 degrees  and -90 degrees ). Patients underwent tissue Doppler
      imaging (TDI) to measure time interval between onset of QRS complex and peak
      systolic velocity in ejection period (Q-peak) at basal segments of septal,
      inferior, lateral and anterior walls, as expression of local timing of mechanical
      activation. RESULTS: Thirty patients (mean age 70.6years; 19 males) were
      included. Mean left ventricular ejection fraction was 0.28+/-0.06. Mean QRS
      duration was 172.5+/-13.9ms. Fifteen patients showed LBBB with LAD (QRS duration
      173+/-14; EF 0.27+/-0.06). The other 15 patients had LBBB with a normal QRS axis
      (QRS duration 172+/-14; EF 0.29+/-0.05). Among patients with LAD, Q-peak interval
      was significantly longer at the anterior wall in comparison to each other walls
      (septal 201+/-46ms, inferior 242+/-58ms, lateral 267+/-45ms, anterior 302+/-50ms;
      p<0.0001). Conversely, in patients without LAD Q-peak interval was longer at
      lateral wall, when compared to each other (septal 228+/-65ms, inferior 250+/
      64ms, lateral 328+/-98ms, anterior 291+/-86ms; p<0.0001). CONCLUSIONS: Patients
      with heart failure, presenting LBBB and LAD, show a specific pattern of
      ventricular asynchrony, with latest activation at anterior wall. This finding
      could affect target vessel selection during CRT procedures in these patients.

PMID- 29174023
TI  - Antibiotic treatment of asymptomatic bacteriuria prior to hip and knee
      arthroplasty; a systematic review of the literature.
AB  - BACKGROUND: There is significant debate as to whether routine antibiotic
      treatment of asymptomatic bacteriuria (ASB) in arthroplasty patients reduces the
      risk of subsequent PJI. No previous systematic reviews have been undertaken on
      this subject. The aim of this systematic review was to investigate whether
      antibiotic treatment of asymptomatic bacteriuria in arthroplasty patients reduces
      the risk of prosthetic joint infection and to investigate whether the organisms
      cultured in peri-operative urine samples are the same as those responsible for
      subsequent prosthetic joint infections. METHODS: Medline and SCOPUS databases
      were searched using a systematic search strategy. Inclusion Criteria were that
      the paper must present data detailing infection rates in patients with
      asymptomatic bacteriuria versus those without and must provide information on
      infection rates for ASB patients treated with antibiotics versus those not
      treated. Non-English Language papers and Conference Abstracts in which a full
      manuscript was not published were excluded. Two hundred and five papers were
      returned - three papers were included in the review, comprising 3267 patients.
      RESULTS: Only 3 studies met the inclusion criteria. The published literature does
      not support the routine antibiotic treatment of asymptomatic bacteriuria in
      arthroplasty patients. The organisms responsible for peri-prosthetic joint
      infection in patients with pre-operative asymptomatic bacteriuria are different
      from that cultured in their urine during the pre-operative period. This means
      that, although biologically possible, a direct causal relationship appears
      extremely unlikely. CONCLUSIONS: The evidence base supporting antibiotic
      treatment of asymptomatic bacteriuria prior to arthroplasty surgery is weak.
      Given the lack of evidence to support a direct causal relationship, routine
      antibiotic treatment of ASB in arthroplasty patients is not justified.

PMID- 29174024
TI  - In vitro antitumor effect of a lignan isolated from Combretum fruticosum,
      trachelogenin, in HCT-116 human colon cancer cells.
AB  - The use of natural products in therapeutics has been growing over the years.
      Lignans are compounds with large pharmaceutical use, which has aroused interest
      in the search for new drugs to treat diseases. The present study evaluated the
      cytotoxicity of (-)-trachelogenin, a dibenzylbutyrolactone type lignan isolated
      from Combretum fruticosum, against several tumor and non-tumor cell lines using
      the MTT assay and its possible mechanism of action. (-)-Trachelogenin showed IC50
      values ranging of 0.8-32.4MUM in SF-295 and HL-60 cell lines, respectively and
      IC50 values >64MUM in non-tumor cell lines. (-)-trachelogenin persistently
      induced autophagic cell death, with cytoplasmic vacuolization and formation of
      autophagosomes mediated by increasing LC3 activation and altering the expression
      levels of Beclin-1.

PMID- 29174025
TI  - A systematic review of the effect of dietary saturated and polyunsaturated fat on
      heart disease.
AB  - AIMS: Over the last 7 years there has been intense debate about the advice to
      reduce saturated fat and increase polyunsaturated fat to reduce CVD risk. The aim
      of this review was to examine systematic reviews and meta-analyses since 2010 on
      this topic plus additional cohort studies and interventions not included in these
      reviews. DATA SYNTHESIS: High saturated and trans fat intake (which elevates LDL
      like saturated fat) in the Nurses and Health Professional Follow-Up Studies
      combined is associated with an 8-13% higher mortality and replacement of
      saturated fat with any carbohydrate, PUFA and MUFA is associated with lower
      mortality with PUFA being more effective than MUFA (19% reduction versus 11%).
      With CVD mortality only PUFA and fish oil replacement of saturated fat lowers
      risk with a 28% reduction in CVD mortality per 5% of energy. Replacing saturated
      fat with PUFA or MUFA is equally effective at reducing CHD events and replacement
      with whole grains will lower events while replacement with sugar and starch
      increases events. Replacement of saturated fat with carbohydrate has no effect on
      CHD events or death. Only PUFA replacement of saturated fat lowers CHD events and
      CVD and total mortality. Replacing saturated fat with linoleic acid appears to be
      beneficial based on the Hooper Cochrane meta-analysis of interventions although
      other analyses with fewer studies have shown no effect. CONCLUSIONS: Reducing
      saturated fat and replacing it with carbohydrate will not lower CHD events or CVD
      mortality although it will reduce total mortality. Replacing saturated fat with
      PUFA, MUFA or high-quality carbohydrate will lower CHD events.

PMID- 29174026
TI  - Adverse events with sodium-glucose co-transporter-2 inhibitors: A global analysis
      of international spontaneous reporting systems.
AB  - BACKGROUND AND AIMS: We assessed post-marketing safety of sodium-glucose co
      transporter-2 inhibitors (SGLT2-Is) by analyzing adverse events (AEs) reported in
      international pharmacovigilance databases. METHODS AND RESULTS: Eudravigilance,
      WHO-Vigibase (as of Feb 25, 2017) and the FDA Adverse Event Reporting System
      (FAERS, from 2004 to 2016 second quarter) were queried to extract AEs recording
      SGLT2-Is as suspect. Disproportionality analyses (case/non-case method) were
      performed in FAERS by calculating the reporting odds ratios (RORs) from System
      Organ Classes (SOCs) to Preferred Terms (PTs) (precise clinical entities).
      Potential signals were defined by statistically-significant ROR (lower limit of
      the 95% confidence interval - LL95%CI - >1) undetected by literature analysis (as
      of December 2016). SGLT2-Is were recorded in 7972, 19,775, 11,137 reports
      (Eudravigilance, WHO-Vigibase and FAERS, respectively); in FAERS, statistically
      significant ROR emerged for the following SOCs: "infections and infestations" (N
      = 2162; LL95%CI = 3.25), "metabolism and nutrition disorders" (2278; 1.36),
      "renal and urinary disorders" (1665; 2.31), "reproductive system and breast
      disorders" (471; 4.85), "skin and subcutaneous tissue disorders" (1136; 1.52).
      Skin toxicity emerged as potential signal (e.g., rash, photosensitivity,
      urticaria as PTs), both for SGLT2-Is as a class and as individual drugs. Severe
      adverse skin events (81 reports, 7% of the skin cases) mainly occurred in females
      aged 18-65 using SGLT2-Is as single antidiabetic regimen. CONCLUSION: Among
      antidiabetics, SGLT2-Is are associated with higher reporting of infections,
      metabolism, renal and reproductive AEs, corroborating clinical trial evidence.
      Their large reporting patterns and the unexpected signal of skin toxicity justify
      active vigilance by clinicians and "real-time" monitoring by pharmacovigilance
      experts.

PMID- 29174027
TI  - Association of serum fibroblast growth factor 19 levels with visceral fat
      accumulation is independent of glucose tolerance status.
AB  - BACKGROUND AND AIMS: Recent studies suggested that circulating fibroblast growth
      factor (FGF) 19 levels might be associated with the fat content and distribution,
      and varied with different glucose tolerance status. This study aimed to
      investigate the association of serum FGF19 levels with obesity and visceral fat
      accumulation in a Chinese population with differing glucose tolerance status.
      METHODS AND RESULTS: The 2383 participants were divided into subgroups of glucose
      tolerance status: normal glucose tolerance (NGT, n = 1754), impaired glucose
      regulation (IGR, n = 499), and newly diagnosed diabetes mellitus (DM, n = 130).
      They were further stratified into quartiles of serum FGF19 levels (Q1-Q4).
      Visceral fat area (VFA) and subcutaneous fat area were measured using magnetic
      resonance imaging. FGF19 were detected via quantitative sandwich enzyme-linked
      immunosorbent assay. Serum FGF19 levels showed a downtrend across the NGT, IGR,
      and DM groups (P for trend = 0.016). VFA was an independent and negative factor
      of serum FGF19 levels (standardized beta = -0.108, P = 0.001). After adjustment
      for glucose tolerance status, VFA differed significantly among FGF19 quartiles (P
      < 0.001), showing a downtrend from Q1-Q4. The associations of serum FGF19 levels
      and glucose tolerance status with VFA were independent of each other. After
      adjustment for insulin resistance and secretory function separately, VFA still
      decreased significantly from Q1-Q4 (all P < 0.001). CONCLUSION: Serum FGF19
      levels were related to visceral fat accumulation. Independent of glucose
      tolerance status, serum FGF19 levels were inversely associated with VFA.

PMID- 29174029
TI  - Interrelationship of the rs7903146 TCF7L2 gene variant with measures of glucose
      metabolism and adiposity: The NEO study.
AB  - BACKGROUND AND AIMS: We investigated the interrelationship of rs7903146-T in
      TCF7L2 with measures of glucose metabolism and measures of adiposity. METHODS AND
      RESULTS: This cross-sectional analysis was conducted in 5744 middle-aged
      participants (mean (standard deviation [SD]) age is 55.9 (6.0) years) from the
      Netherlands Epidemiology of Obesity (NEO) Study. Associations between rs7903146-T
      and Type 2 diabetes mellitus (T2D) were assessed with logistic regression.
      Additive (per-allele) associations with measures of glucose metabolism (e.g.,
      fasting insulin) and adiposity (e.g., body mass index [BMI]) were examined with
      multivariable linear regression. In the total study population, rs7903146-T was
      associated with a higher risk of T2D (additive odds ratio: 1.42; 95% confidence
      interval: 1.17; 1.72), and specifically with T2D treated with insulin analogs
      (2.31 [1.19; 4.46]). After exclusion of participants treated with glucose
      lowering medication, rs7903146-T was associated with lower mean insulin
      concentration (additive mean difference: -0.07 SD [-0.14; 0.00]), but not with
      higher mean glucose concentration (0.03 SD [-0.01; 0.07]). Furthermore, rs7903146
      T was associated with, among other measures of adiposity, a lower mean BMI (-0.04
      SD [-0.09; -0.00]), and a lower mean total body fat (-0.04 SD [-0.08; -0.00]).
      The association between rs7903146-T and T2D increased after adjustment for BMI
      (odds ratio: 1.51 [1.24; 1.86]); the association between rs7903146-T and fasting
      insulin diminished after adjustment (-0.05 SD [-0.11; 0.02]). CONCLUSION:
      rs7903146-T is associated with a decreased insulin concentration and increased
      risk of T2D with opposing effects of adjustment for adiposity.

PMID- 29174030
TI  - Position paper on vegetarian diets from the working group of the Italian Society
      of Human Nutrition.
AB  - BACKGROUND: Interest in vegetarian diets is growing in Italy and elsewhere, as
      government agencies and health/nutrition organizations are emphasizing that
      regular consumption of plant foods may provide health benefits and help prevent
      certain diseases. METHODS AND RESULTS: We conducted a Pubmed search, up to
      September, 2015, for studies on key nutrients (proteins, vitamin B12, iron, zinc,
      calcium, vitamin D, and n-3 fatty acids) in vegetarian diets. From 295 eligible
      publications the following emerged: Vegetarians should be encouraged to
      supplement their diets with a reliable source of vitamin B12 (vitamin-fortified
      foods or supplements). Since the plant protein digestibility is lower than that
      of animal proteins it may be appropriate for vegetarians to consume more proteins
      than recommended for the general population. Vegetarians should also be
      encouraged to habitually consume good sources of calcium, iron and zinc -
      particularly vegetables that are low in oxalate and phytate (e.g. Brassicaceae),
      nuts and seeds, and calcium-rich mineral water. Calcium, iron, and zinc
      bioavailability can be improved by soaking, germination, and sour-dough leavening
      that lower the phytate content of pulses and cereals. Vegetarians can ensure good
      n-3 fatty acid status by habitually consuming good sources of a-linolenic acid
      (walnuts, flaxseeds, chia seeds, and their oils) and limiting linoleic acid
      intake (corn and sunflower oils). CONCLUSIONS: Well-planned vegetarian diets that
      include a wide variety of plant foods, and a reliable source of vitamin B12,
      provide adequate nutrient intake. Government agencies and health/nutrition
      organizations should provide more educational resources to help Italians consume
      nutritionally adequate vegetarian diets.

PMID- 29174031
TI  - Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of
      the FDA adverse event report system database.
AB  - BACKGROUND AND AIMS: Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have
      recently been approved for the treatment of type II diabetes mellitus (T2DM). It
      has been proposed that these agents could induce acute renal failure (ARF) under
      certain conditions. This study aimed to evaluate the association between SGLT2
      inhibitors and ARF in the FDA adverse event report system (FAERS) database.
      METHODS AND RESULTS: We analyzed adverse event cases submitted to FAERS between
      January 2013 and September 2016. ARF cases were identified using a structured
      medical query. Medications were identified using both brand and generic names.
      During the period evaluated, 18,915 reports (out of a total of 3,832,015
      registered in FAERS) involved the use of SGLT2-inhibitors. SGLT2-inhibitors were
      reportedly associated with ARF in 1224 of these cases (6.4%), and were defined as
      the "primary" or "secondary" cause of the adverse event in 96.8% of these cases.
      The proportion of reports with ARF among reports with SGLT2 inhibitor was almost
      three-fold higher compared to reports without these drugs (ROR 2.88, 95% CI 2.71
      3.05, p < 0.001). The proportion of ARF reports among cases with SGLT2-inhibitors
      was significantly greater than the proportion of ARF among cases with T2DM
      without SGLT2-inhibitors (ROR 1.68, 95% CI 1.57-1.8, p < 0.001). Among the SGLT2
      inhibitors, canagliflozin was associated with a higher proportion of reports of
      renal failure (7.3%), compared to empagliflozin and dapagliflozin (4.7% and 4.8%
      respectively, p < 0.001). CONCLUSION: SGLT2-inhibitors are associated with an
      increase in the proportion of reports of ARF compared to other medications. SGLT2
      inhibitor agents may differ from one another in their respective risk for ARF.

PMID- 29174032
TI  - Associations between neck symptoms and LDL cholesterol in a cross-sectional
      population-based study.
AB  - BACKGROUND: Studies have reported associations between neck pain and degenerative
      changes in the cervical spine in women, and between neck pain and obesity or
      metabolic syndrome. The present study investigated associations between neck pain
      or stiffness and lipid profiles in subjects recruited from the general population
      of a Japanese community. METHODS: The 1122 volunteers who participated in this
      study included 426 men (age 52.6 +/- 15.5 years; body mass index 23.6 +/- 3.2)
      and 696 women (age 55.3 +/- 15.3 years; body mass index 22.2 +/- 3.4). Each
      subject filled out a questionnaire about any neck pain or neck-shoulder stiffness
      experienced in the previous 3 months. We recorded the following laboratory
      results related to metabolic factors, including lipid profiles: total
      cholesterol, LDL and HDL cholesterol, triglycerides, free fatty acids, glucose,
      and hemoglobin A1c. We conducted logistic and linear regression analyses using
      the prevalence of neck pain or neck-shoulder stiffness as the dependent variable
      and age, sex, body mass index, and laboratory data as independent variables.
      RESULTS: There was no significant difference in the prevalence of neck pain
      between men (20.5%) and women (21.5%). However, the prevalence of neck and
      shoulder stiffness was significantly higher in women (60.3%) than in men (38.0%;
      P < 0.05). Logistic and linear regression analyses showed a significant negative
      correlation between the prevalence of neck pain and LDL cholesterol (odds ratio
      [OR], 0.958; 95% CI, 0.921-0.997), and between the prevalence of neck-shoulder
      stiffness and age (OR, 1.025; 95% CI, 1.013-1.038) and gender (OR, 0.362; 95% CI,
      0.25-0.494). CONCLUSION: LDL cholesterol was correlated with neck pain in this
      cross-sectional population-based study.

PMID- 29174033
TI  - Anti-cancer and anti-angiogenic effects of partially purified lectin from
      Praecitrullus fistulosus fruit on in vitro and in vivo model.
AB  - Praecitrullus fistulosus, belonging to the family of Cucurbitaceae is a tropical
      vegetable and medicinal plant, grown and consumed extensively in subtropical
      countries, including the subcontinent India. However, there are limited reports
      on the medicinal properties of the plant and need to be explored. The lectin
      identified from the fruit sap of Praecitrullus fistulosus, named as PfLP,
      possesses potent agglutinating activity against trypsinized rabbit erythrocytes
      and exhibited its functional role against tumor progression, on in vitro &in vivo
      models. Experimental results revealed that PfLP shows a promising cytotoxic
      effect against multiple cancer cell lines. Further, we examined the in vivo
      anticancer and anti-angiogenic properties of PfLP against EAC bearing mice. PfLP
      treatment resulted in tumor growth inhibition and increased the life-span of the
      EAC bearing mice, without showing any detectable side effects, as revealed by
      histological parameters. Further, a significant decrease in the ascites VEGF
      secretion level was parallel with a drastic reduction in tumoral neovasculature
      as evidence for angiogenic parameters. Gelatin zymogram study reveals that PfLP
      inhibits metalloproteinases (MMP-2 & MMP-9) activity in order to execute its anti
      angiogenic effect. PfLP has also inducing apoptosis, in cancer cells was revealed
      by DNA fragmentation assay followed by Giemsa and AO/EBr staining method, showed
      the apoptotic bodies and condensed nuclei compared to control cells. More
      interestingly, PfLP did not exhibit any adverse side effects or secondary
      complications in normal mice. These results clearly exhibit the potential role of
      PfLP in regressing the tumor progression by targeting angiogenesis and inducing
      cell death in mouse transplantable tumor.

PMID- 29174028
TI  - Inflammation in metabolically healthy and metabolically abnormal adolescents: The
      HELENA study.
AB  - BACKGROUND AND AIMS: Inflammation may influence the cardio-metabolic profile
      which relates with the risk of chronic diseases. This study aimed to assess the
      inflammatory status by metabolic health (MH)/body mass index (BMI) category and
      to assess how inflammatory markers can predict the cardio-metabolic profile in
      European adolescents, considering BMI. METHODS AND RESULTS: A total of 659
      adolescents (295 boys) from a cross-sectional European study were included.
      Adolescents were classified by metabolic health based on age- and sex-specific
      cut-off points for glucose, blood pressure, triglycerides, high density
      cholesterol and BMI. C-reactive protein (CRP), tumor necrosis factor alpha (TNF
      alpha), interleukin (IL-6), complement factors (C3, C4) and cell adhesion
      molecules were assessed. RESULTS: Metabolically abnormal (MA) adolescents had
      higher values of C3 (p < 0.001) and C4 (p = 0.032) compared to those
      metabolically healthy (MHy). C3 concentrations significantly increased with the
      deterioration of the metabolic health and BMI (p < 0.001). Adolescents with
      higher values of CRP had higher probability of being in the overweight/obese-MH
      group than those allocated in other categories. Finally, high C3 and C4
      concentrations increased the probability of having an unfavorable metabolic/BMI
      status. CONCLUSIONS: Metabolic/BMI status and inflammatory biomarkers are
      associated, being the CRP, C3 and C4 the most related inflammatory markers with
      this condition. C3 and C4 were associated with the cardio-metabolic health
      consistently.

PMID- 29174034
TI  - Panax notoginseng saponins reduce high-risk factors for thrombosis through
      peroxisome proliferator-activated receptor -gamma pathway.
AB  - The classic Virchow theory suggests that blood stasis, hypercoagulability and
      endothelial dysfunction are three major factors that cause venous thrombosis
      (VT). It is a complicated biological process involved multi-factors. Platelet
      plays a central role and participates in multiple links of this process. Panax
      notoginseng saponins (PNS), the principal constituents derived from panax
      notoginseng, has been widely described for its anti-platelet activity. However,
      its potential mechanism against platelet aggregation has not been clarified. In
      this present study, we evaluated the anti-platelet effects of PNS on thrombin
      induced platelet activation and its possible molecular mechanism of action, and
      further explored the therapeutic action of PNS on thrombin induced
      hypercoagulability in rat. Our results showed that PNS treatment inhibited
      platelet aggregation induced by thrombin, which was accompanied with over
      expression of Peroxisome proliferator-activated receptor gamma (PPAR-gamma)
      protein, mRNA and upregulation of phosphatidylinositol 3 kinase (PI3K)/ protein
      kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) pathway in platelet, and
      this effect could be reversed by PPAR-gamma inhibitor T0070907. In vivo, PNS
      significantly reversed thrombin-induced hypercoagulable state in rat which was
      accompanied by PPAR-gamma protein and mRNA upregulation in rat lung. In
      conclusion, these data suggested that PNS could suppress thrombin-induced
      platelet aggregation in vitro and effectively improve hypercoagulable state in
      vivo and PNS-induced activation of PPAR-gamma and its downstream PI3K/Akt/eNOS
      pathway played the central role.

PMID- 29174035
TI  - Effects of standard ethanolic extract from Erythrina velutina in acute cerebral
      ischemia in mice.
AB  - The objective of this study was to verify a possible neuroprotective effect of
      the ethanolic extract of Erythrina velutina (EEEV). Male Swiss mice were
      submitted to transient cerebral ischemia by occlusion of both carotid arteries
      for 30 min and treated for 5 days with EEEV (200 or 400 mg/kg) or Memantine (MEM)
      10 mg/kg, with initiation of treatment 2 or 24 h after Ischemia. On the 6th day
      after the induction of ischemia, the animals were submitted to evaluation of
      locomotor activity and memory and then sacrificed. The brains were dissected for
      the removal of the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST)
      for determination of amino acid concentrations. In the step down and Y-maze
      tests, ischemia caused damage to the animals and treatment with EEEV or MEM
      reversed this effect. The animals submitted to ischemia also showed memory
      deficit in the object recognition test, an effect that was reverted by EEEV400
      and MEM10. Amino acid dosage showed an increase in excitatory amino acid
      concentrations in the PFC of the ischemic animals and this effect was reversed by
      the treatment with EEEV400/24H. Regarding the inhibitory amino acids, ischemia
      caused an increase of taurine in the PFC while treatment with MEM10/24H or
      EEEV400/24H reversed this effect. In HC, an increase in excitatory amino acids
      was also observed in ischemiated animals having treatment with EEEV200/2H or
      EEEV400/24H reversed this effect. Similar effect was also observed in the same
      area in relation to the inhibitory amino acids with treatment with MEM10/24H or
      EEEV400/24H. In the ST, ischemia was also able to cause an increase in excitatory
      amino acids that was reversed more efficiently by the treatments with MEM10/24H
      and EEEV200. Also in this area, an increase of taurine and GABA was observed and
      only the treatment with EEEV200/2H showed a reversion of this effect. In view of
      these findings, EEEV presents a neuroprotective effect possibly due to its action
      on amino acid concentrations, and is therefore a potential therapeutic tool in
      reducing the damage caused by ischemia.

PMID- 29174036
TI  - Increase in renal erythropoietin receptors in diabetic rats is mainly mediated by
      hyperglycemia associated with the STAT3/GATA-1 signaling pathway.
AB  - Erythropoietin (EPO) produces cytoprotection in many tissues by activating the
      EPO receptor (EPOR); these effects include anti-oxidative stress and the
      inhibition of apoptosis in renal tubular cells. Moreover, EPO is clinically used
      in diabetic patients who suffer from chronic renal disease. However, the effect
      of hyperglycemia on renal EPOR expression remains unknown. Therefore, we
      determined the changes in renal EPOR expression in diabetic rats and investigated
      the role of potential factors using cultured cells. Streptozotocin-induced
      hyperglycemic rats (STZ rats) treated with insulin or phloridzin to correct
      hyperglycemia were used to investigate treated with insulin or phloridzin to
      correct hyperglycemia were used to investigate the EPOR changes. Potential
      factors, including the transducer and activator of transcription 3 (STAT3) and
      GATA binding protein 1 (GATA1), were identified in cultured NRK-49F cells after
      incubation with high glucose (HG) levels to mimic diabetic animals. Renal EPOR
      expression was reduced by insulin and phloridzin in STZ rats, and hyperglycemia
      recovered. An increase in EPORs was also reproduced in hyperglycemia-exposed NRK
      49F cells and HK-2 cells, which showed a higher expression of STAT3 or GATA1.
      Furthermore, the application of siRNA specific to STAT3 or GATA1 attenuated the
      higher expression of EPORs in HG-incubated NRK-49F cells. Moreover, stattic
      administered at a dose that was sufficient to inhibit STAT3 restored the level of
      renal EPORs in diabetic rats. Taken together, the expression of renal EPORs is
      increased by hyperglycemia via the STAT3/GATA1 pathway and has been characterized
      in both diabetic rats and cultured cells.

PMID- 29174037
TI  - Cellular senescence and liver disease: Mechanisms and therapeutic strategies.
AB  - Cellular senescence is a fundamental cell fate caused by several cellular
      injuries which results in irreversible cell cycle arrest yet remaining
      metabolically active across all species. Cellular senescence not only can prevent
      tumor occurrence by inhibiting the proliferation of injured cells, but also can
      affect the surrounding cells through the senescence-associated secretory
      phenotype (SASP). Attractively, accumulating evidence shows that cellular
      senescence is closely related to various liver diseases. Therapeutic
      opportunities based on targeting senescent cells and the SASP are considered to
      be potential strategy for liver diseases. However, although research on cell
      senescence has attracted widespread attention, the overview on detailed mechanism
      and biological function of cell senescence in liver disease is still largely
      unknown. The present review summarizes the specific role of cell senescence in
      various liver diseases, and updates the molecular mechanisms underlying cell
      senescence. Moreover, the review also explores new strategies for prevention and
      treatment of liver disease through promoting senescence or counteracting
      excessive pathological senescence.

PMID- 29174038
TI  - Lycopene amends LPS induced oxidative stress and hypertriglyceridemia via
      modulating PCSK-9 expression and Apo-CIII mediated lipoprotein lipase activity.
AB  - This study was undertaken to uncover the regulatory role of lycopene in targeting
      lipopolysaccharide (LPS) induced oxidative stress and inflammatory cascades and
      subsequent regulation of proprotein convertase subtilisin/kexin type-9 (PCSK-9)
      expression via sterol regulatory element binding protein-2 (SREBP-2) and
      hepatocyte nuclear factor-1alpha (HNF-1alpha). Further, protein-protein
      interaction (PPI) studies for Lycopene-Apo-CIII complex against lipoprotein
      lipase (LPL) were also performed to assess its regulatory role behind the
      enhanced circulatory TG/TRLs clearance. Lycopene treatment down-regulated
      hepatocyte PCSK-9 expression via down-regulation of HNF-1alpha, whereas, LDL
      receptor (LDL-R) was up-regulated by subsequent up-regulation of SREBP-2. PPI
      studies showed that lycopene diminishes the affinity of Apo-CIII to complex with
      LPL (DeltaG: -917.1 Kcal/mol) resulting in increased LPL functionality and TRLs
      clearance. Moreover, lycopene also ameliorated LPS stimulated oxidative-stress
      via enhanced total antioxidant and HDL associated PON-1 activity in addition to
      down-regulate the expression and plasma level of inflammatory mediators. Based on
      above findings, we concluded that lycopene exhibits dual role in targeting LPS
      induced oxidative stress and hypertriglyceridemia via down-regulation of PCSK-9,
      making greater no. of surface LDL-R available for LPS processing and clearance,
      as well as increased LPL activity through inhibition of Apo-CIII.

PMID- 29174039
TI  - Lavatera critica, a green leafy vegetable, controls high fat diet induced hepatic
      lipid accumulation and oxidative stress through the regulation of lipogenesis and
      lipolysis genes.
AB  - BACKGROUND: Lipid accumulation is the most vital risk factor for inducing
      nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. Thus, the
      development of novel drugs is urgently needed to control obesity related
      diseases. OBJECTIVE: Here, we investigated the protective role of Lavatera
      critica (LC), a green vegetable, in male C57BL/6J mice fed with high fat (HF)
      diet for 10 weeks to induce hepatic lipid accumulation and oxidative cellular
      damage. RESULTS: After oral administration of chloroform (CFLC), ethyl acetate
      (EFLC), or methanol (MFLC) fractions of Lavatera critica to the HF group, EALC
      alone significantly reduced the activities of hepatic markers such as alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST); moreover, the
      results showed that 50 mg/kg dose has the maximum activity. Thus, this active
      dose of EFLC was used for further analysis. Moreover, EFLC reduced the level of
      hepatic triglycerides (TG), total cholesterol (TC), free fatty acids (FFA), and
      prevented further increase in the body weight. Intriguingly, EFLC treatment also
      reversed the mRNA expression of fatty acid oxidative genes, such as peroxisome
      proliferator activated receptor-alpha (PPAR-alpha), carnitine
      palmitoyltransferase-1 (CPT-1), and acetyl-CoA carboxylase (ACO), and fatty acid
      synthesis genes such as fatty acid synthase (FAS), sterol-regulatory-element
      binding protein-1c (SREBP-1c), and acetyl-CoA carboxylase (ACC). Furthermore,
      EFLC treatment also decreased the production of oxidative stress biomarkers, such
      as conjugated diene (CD), thiobarbituric acid reactive substances (TBARS), and
      lipid hydroperoxide (LOOH), and significantly enhanced the level of enzymatic
      antioxidants, such as glutathione peroxidase (GPx), superoxide dismutase (SOD),
      and catalase (CAT), as well as non-enzymatic antioxidants, such as reduced
      glutathione (GSH), vitamin C, and vitamin E in the liver. CONCLUSION: Taken
      together, we conclude that EFLC has a protective effect against HF diet induced
      hepatic lipid accumulation and oxidative cellular damage through the regulation
      of lipogenesis and lipolysis genes.

PMID- 29174040
TI  - The impact of the 2008 economic crisis on the increasing number of young
      psychiatric inpatients.
AB  - BACKGROUND: Little is published about the impact of the 2008 economic crisis on
      mental health services in Spain. METHOD: An interrupted time series analysis was
      conducted to investigate a potential short-term association between the 2008
      economic crisis and the number of psychiatric hospital admissions. The timing of
      the intervention (April 2008) was based on observed changes in Gross Domestic
      Product (GDP). Data on 1,152,880 psychiatric inpatients from the national
      Hospital Morbidity Survey, 69 months before and after the onset of the economic
      crisis (April 2008), were analyzed. RESULTS: Age-adjusted psychiatric (ICD9 290
      319) hospital discharge rates significantly increased from April 2008, matching
      the onset of the crisis, especially for inpatients aged 15-24 years old and to a
      less extend for inpatients aged 25-34 years old. Other age groups were not
      affected. There was a significant increase in diagnoses for disturbance of
      conduct and emotions, depression, neurotic and personality disorders and alcohol
      and drug disorders; however, diagnoses for mental retardation and organic
      psychosis for 15-34 years old inpatients were unaffected. CONCLUSIONS:
      Psychiatric hospital admissions abruptly increased in April 2008, coinciding with
      the onset of the economic crisis. We identified age groups and diagnoses
      affected. Increased hospitalizations were found only at the age-ranges most
      affected by the rise in unemployment. The diagnoses affected were those most
      sensitive to environmental changes.

PMID- 29174041
TI  - Quasi-static pulmonary P-V curves of patients with ARDS, Part I:
      Characterization.
AB  - Quasi-static, pulmonary pressure-volume (P-V) curves are combined with a
      respiratory system model to analyze characteristics of patients with acute
      respiratory distress syndrome (ARDS). It is shown that there exist distinct
      differences between healthy- and injured-respiratory system in the order of
      magnitudes of parameters of their P-V model equation. Four stages of ARDS (Early
      ARDS, Deep knee, Advanced ARDS and Baby lung) are defined quantitatively in terms
      of these parameters.

PMID- 29174042
TI  - Lipid Microbubbles as Ultrasound-Stimulated Oxygen Carriers for Controllable
      Oxygen Release for Tumor Reoxygenation.
AB  - Microbubbles are proposed as a potentially novel method for oxygen delivery in
      vivo in initial studies. The lack of commercial microbubbles for oxygen delivery
      in preclinical research prompted us to fabricate an oxygen-loaded lipid
      microbubble. We aimed to extend the innovative strategy to modulate the tumor
      hypoxic microenvironment, using microbubbles intravenously as an oxygen carrier
      for the controllable tumor-specific delivery of oxygen by ultrasound (US). In our
      experiment, an oxygen-loaded lipid-coated microbubble (OLM) with mixed gas (O2/C3
      F8, 5:1 v/v) was fabricated and exhibited a higher rate of oxygen release to a
      desaturated solution through burst by US than that in the absence of US. Although
      in in vivo studies, OLMs could be imaged and triggered by US to elevate the pO2
      level in the breast VX2 tumor dramatically within a matter of minutes. The added
      presence of US-activated OLMs elicited a nearly six-fold increase in pO2 levels
      within 1 min compared with that of the pre-injection. Owing to the high oxygen
      payload, great acoustic stability and acoustic properties, OLMs may be proposed
      as an ideal radio-sensitizer. We conclude that oxygen release mediated by
      ultrasound-targeted microbubble destruction is feasible and shows potential in
      image-guided, site-specific cancer radiotherapy.

PMID- 29174043
TI  - Quantitative Evaluation of Denervated Muscle Atrophy with Shear Wave Ultrasound
      Elastography and a Comparison with the Histopathologic Parameters in an Animal
      Model.
AB  - This study explored the efficacy of shear wave ultrasound elastography (SWUE) for
      quantitative evaluation of denervated muscle atrophy in a rabbit model. The
      elastic modulus of the triceps surae muscle was measured with SWUE and compared
      with histopathologic parameters at baseline and at various post-denervation times
      (2, 4 and 8 wk) with 10 animals in each group. Our results revealed that the
      elastic modulus of denervated muscle was significantly lower at 2 wk but higher
      at 8 wk compared with that at the baseline (p <0.05), and no significant
      difference was found between the elastic modulus at 4 wk and that at the baseline
      (p > 0.05). The wet-weight ratio and the muscle fiber cross-sectional area of the
      denervated muscle decreased gradually during the 8 wk post-denervation together
      with a gradual increase of the collagen fiber area (p <0.05). In conclusion, SWUE
      was useful for quantitative evaluation of muscle denervation. The decreased
      elastic modulus might be an early sign of denervated muscle atrophy.

PMID- 29174044
TI  - Repeatability of Contrast-Enhanced Ultrasonography of the Kidneys in Healthy
      Cats.
AB  - Contrast-enhanced ultrasound can be used to image and quantify tissue perfusion.
      It holds great potential for the use in the diagnosis of various diffuse renal
      diseases in both human and veterinary medicine. Nevertheless, the technique is
      known to have an inherent relatively high variability, related to various factors
      associated with the patient, the contrast agent and machine settings. Therefore,
      the aim of this study was to assess week-to-week intra- and inter-cat variation
      of several perfusion parameters obtained with CEUS of both kidneys of 12 healthy
      cats. Repeatability was determined by calculating the coefficient of variation
      (CV). The contrast-enhanced ultrasound parameters with the lowest variation for
      the renal cortex were time-to-peak (CV 6.0%), rise time (CV 13%), fall time (CV
      19%) and mean transit time (24%). Intensity-related parameters and parameters
      related to the slope of the time-intensity curve had a CV of >35%. Lower
      repeatability was present for perfusion parameters derived from the renal medulla
      compared with the renal cortex. Normalization to the inter-lobar artery does not
      cause a reduction in variation. In conclusion, time-related parameters for the
      cortex show a reasonable repeatability; whereas poor repeatability is present for
      intensity-related parameters and parameters related to in- and outflow of
      contrast agent. Poor repeatability is also present for all perfusion parameters
      for the renal medulla, except for time to peak, which has a good repeatability.

PMID- 29174046
TI  - Simulation as a learning tool for continuing education on cardiorespiratory
      arrest.
AB  - OBJECTIVE: To evaluate the level of knowledge and the degree of satisfaction
      obtained through continuous training in simulation-debriefing methods as a
      learning tool in the care of cardiopulmonary arrest (CPA). METHOD: A quasi
      experimental study. Evaluation by ad hoc questionnaire (pre and post, and
      reassessment at 4 months) to all professionals (physicians and nurses) who passed
      any of the 6 editions of the course: 'Simulation of situations of cardiopulmonary
      arrest or peri-arrest in hospitalisation units'. Descriptive and inferential
      statistics. RESULTS: 133 participants, 16 physicians, and 117 nurses. Before the
      course started, the level of knowledge was 78.5%, at the end of training it was
      94.6% (P<.001), and after 4 months, it was 88% (P<.05). The satisfaction achieved
      was 91.8% at the end of the course, and subsequently 88.4%; this was significant
      (P<.05) among the younger professionals, with less experience and with a
      temporary contract. Eighty one point two percent of the participants expressed
      that they changed the way they acted during a cardiopulmonary arrest.
      CONCLUSIONS: Continuous education in CPA, performed through simulation
      debriefing, is consolidated in our field as an effective tool to acquire a
      suitable level of knowledge that lasts over time. The level of satisfaction
      achieved was high since this method of learning meets the expectations of the
      professionals and resembles real care practice.

PMID- 29174045
TI  - Effect of Temperature on the Size Distribution, Shell Properties, and Stability
      of Definity(r).
AB  - Physical characterization of an ultrasound contrast agent (UCA) aids in its safe
      and effective use in diagnostic and therapeutic applications. The goal of this
      study was to investigate the impact of temperature on the size distribution,
      shell properties, and stability of Definity(r), a U.S. Food and Drug
      Administration-approved UCA used for left ventricular opacification. A Coulter
      counter was modified to enable particle size measurements at physiologic
      temperatures. The broadband acoustic attenuation spectrum and size distribution
      of Definity(r) were measured at room temperature (25  degrees C) and physiologic
      temperature (37  degrees C) and were used to estimate the viscoelastic shell
      properties of the agent at both temperatures. Attenuation and size distribution
      was measured over time to assess the effect of temperature on the temporal
      stability of Definity(r). The attenuation coefficient of Definity(r) at 37 
      degrees C was as much as 5 dB higher than the attenuation coefficient measured at
      25  degrees C. However, the size distributions of Definity(r) at 25  degrees C
      and 37  degrees C were similar. The estimated shell stiffness and viscosity
      decreased from 1.76 +/- 0.18 N/m and 0.21 * 10-6 +/- 0.07 * 10-6 kg/s at 25 
      degrees C to 1.01 +/- 0.07 N/m and 0.04 * 10-6 +/- 0.04 * 10-6 kg/s at 37 
      degrees C, respectively. Size-dependent differences in dissolution rates were
      observed within the UCA population at both 25  degrees C and 37  degrees C.
      Additionally, cooling the diluted UCA suspension from 37  degrees C to 25 
      degrees C accelerated the dissolution rate. These results indicate that although
      temperature affects the shell properties of Definity(r) and can influence the
      stability of Definity(r), the size distribution of this agent is not affected by
      a temperature increase from 25  degrees C to 37  degrees C.

PMID- 29174047
TI  - Neonatal nurses' perceptions of pain management.
AB  - OBJECTIVES: To describe the perceptions of nurses in neonatal units on pain
      management, meet the educational profile and describe the use of pain assessment
      tools and non-pharmacological management for treatment. METHODS: Cross-sectional
      descriptive multicentre study, developed during the months of February to
      September 2015, in the neonatology services of three hospitals at the Community
      of Madrid, Spain. Data collection was performed through an ad hoc questionnaire
      on paper or electronically using Survey Monkey platform. RESULTS: The sample
      consisted of 142 professionals, with a response rate of 55%: 47.9% (68) confirmed
      they had received specific training in pain management; 39.5% (56) stated that
      pain is regularly assessed in the unit; only 43.6% reported using validated
      scales, the most used being the Premature Infant Pain Profile (PIPP). As for the
      non-pharmacological management, swaddling and non-nutritive sucking it is the
      most used, followed by sucrose. Intravenous cannulation was identified as the
      most painful procedure. CONCLUSIONS: Pain management is in the process of
      improvement, because of training and because there is little pain assessment
      using validated scales. The improvement in the use of non-pharmacological
      management for the relief of pain in minor procedures is noteworthy.

PMID- 29174048
TI  - Degradation of 2,4-dichlorophenol by activating persulfate and peroxomonosulfate
      using micron or nanoscale zero-valent copper.
AB  - The ability of persulfate (PS) and peroxymonosulfate (PMS) activated by micron or
      nanoscale zero-valent copper (ZVC or nZVC) to degrade 2,4-dichlorophenol (2,4
      DCP) was quantified under various conditions. Mechanism investigation revealed
      that PS and PMS accelerated the corrosion of ZVC or nZVC to release Cu+ under
      acidic conditions. The in-situ generated Cu+ further decomposed PS or PMS to
      produce SO4- and OH, which then dramatically degraded 2,4-DCP. The kobs for 2,4
      DCP removal followed pseudo-first-order kinetics, kobs of ZVC/PMS and nZVC/PMS
      systems were 10~30 times greater than these in ZVC/PS and nZVC/PS systems. The
      nZVC/PMS system was most effective to remove 2,4-DCP which even did better than
      the nZVI/PMS system, with rate constant values ranging from 0.041 to 1.855min-1.
      At higher pH ZVC is ineffective, but nZVC can activate PS and PMS to
      significantly degrade 2,4-DCP at pH up to 7.3. The 2,4-DCP degradation pathway
      was found to involve dechloridation, dehydrogenation, hydroxylation, ring open
      and mineralization. 56.7% and 45.3% of TOC removals were respectively obtained in
      the ZVC/PMS and nZVC/PMS systems within 120min. This study helps to comprehend
      the application of zero-valent metals in reactive radicals-based oxidation
      processes and the reactivity of Cu+ as an activator of PS and PMS.

PMID- 29174049
TI  - Neural responses to one's own name under mortality threat.
AB  - Recent behavioral research has shown evidence for greater inclination to avoid
      symbolic cues of mortality threats in nonbelievers than Christians. However, the
      neurocognitive mechanisms underlying religious influences on behavioral tendency
      to avoid mortality threats remain unknown. We tested the hypothesis of distinct
      arousal/attention-related brain responses to self-related information under
      mortality in nonbelievers and Christians. We recorded event-related brain
      potentials (ERPs) from Christians and nonbelievers while they viewed their own
      names and a stranger's name (i.e., Zuma) that flashed around a cue word (i.e.,
      death, pain or life) located at the center of a screen. While own name vs. a
      stranger's name induced faster responses and larger P3 amplitudes, the P3
      amplitudes to own name showed distinct patterns of modulations by the cue words
      in nonbelievers and Christians. Specifically, own name elicited larger P3
      amplitudes in the death than pain/life cue conditions in nonbelievers but not in
      Christians. Moreover, the differential P3 amplitude to own names in the death vs.
      life cue conditions predicted greater inclination to avoid mortality threats in
      nonbelievers but not in Christians. Our findings provide a neurocognitive account
      of increased behavioral tendency to avoid mortality threats in nonbelievers than
      in Christians.

PMID- 29174050
TI  - Phonological working memory and FOXP2.
AB  - The discovery and description of the affected members of the KE family (aKE)
      initiated research on how genes enable the unique human trait of speech and
      language. Many aspects of this genetic influence on speech-related cognitive
      mechanisms are still elusive, e.g. if and how cognitive processes not directly
      involved in speech production are affected. In the current study we investigated
      the effect of the FOXP2 mutation on Working Memory (WM). Half the members of the
      multigenerational KE family have an inherited speech-language disorder,
      characterised as a verbal and orofacial dyspraxia caused by a mutation of the
      FOXP2 gene. The core phenotype of the affected KE members (aKE) is a deficiency
      in repeating words, especially complex non-words, and in coordinating oromotor
      sequences generally. Execution of oromotor sequences and repetition of
      phonological sequences both require WM, but to date the aKE's memory ability in
      this domain has not been examined in detail. To do so we used a test series based
      on the Baddeley and Hitch WM model, which posits that the central executive (CE),
      important for planning and manipulating information, works in conjunction with
      two modality-specific components: The phonological loop (PL), specialized for
      processing speech-based information; and the visuospatial sketchpad (VSSP),
      dedicated to processing visual and spatial information. We compared WM
      performance related to CE, PL, and VSSP function in five aKE and 15 healthy
      controls (including three unaffected members of the KE family who do not have the
      FOXP2 mutation). The aKE scored significantly below this control group on the PL
      component, but not on the VSSP or CE components. Further, the aKE were impaired
      relative to the controls not only in motor (i.e. articulatory) output but also on
      the recognition-based PL subtest (word-list matching), which does not require
      speech production. These results suggest that the aKE's impaired phonological WM
      may be due to a defect in subvocal rehearsal of speech-based material, and that
      this defect may be due in turn to compromised speech-based representations.

PMID- 29174051
TI  - Body mass estimation from the skeleton: An evaluation of 11 methods.
AB  - Estimating an individual body mass (BM) from the skeleton is a challenge for
      forensic anthropology. However, identifying someone's BMI (Body Mass Index)
      category, i.e. underweight, normal, overweight or obese, could contribute to
      identification. Individual BM is also known to influence the age-at-death
      estimation from the skeleton. Several methods are regularly used by both
      archaeologists and forensic practitioners to estimate individual BM. The most
      commonly used methods are based on femoral head breadth, or stature and bi-iliac
      breadth. However, those methods have been created from mean population BMs and
      are therefore meant to estimate the average BM of a population. Being that they
      are based on individual BM data and estimated femoral cortical areas, the newest
      published methods are supposed to be more accurate. We evaluated the accuracy and
      reliability of the most commonly used and most recent BM estimation methods
      (n=11) on a sample of 64 individuals. Both sexes and all BMI categories are
      represented, as well as a wide range of BM. Ages in this sample range from 20 to
      87 years of age. Absolute and real differences between actual BM and estimated BM
      were assessed; they determined the accuracy for individual BM estimation and for
      average BM estimation of a population, respectively. The proportion of the sample
      whose estimated BM falls within +/-10% and +/-20% of their actual BM determines
      the reliability of the methods in our sample for, respectively, individual BM
      estimation and average BM of a population. The tested methods result in an
      absolute difference of 11kg-26kg+/-10kg with regards to prediction of individuals
      actual BM. The real differences are very variable from method to method, ranging
      from -14kg to 25kg. None of the tested methods is able to estimate BM of half of
      the sample within +/-10% of their actual BM but most of them can estimate BM of
      more than half of the sample within +/-20% of their actual BM. The errors
      increase with increasing BM, demonstrating a bias in all the methods. No bone
      variable tested correlated with BM. BMI categories were correctly predicted for
      less than 50% of the sample in most cases. In conclusion, our study demonstrates
      that the 11 methods tested are not suited for estimating individual BM or for
      predicting BMI categories. However, they are accurate and reliable enough for
      estimating the average BM of a population.

PMID- 29174052
TI  - Development and validation of a Partial Least Squares-Discriminant Analysis (PLS
      DA) model based on the determination of ethyl glucuronide (EtG) and fatty acid
      ethyl esters (FAEEs) in hair for the diagnosis of chronic alcohol abuse.
AB  - The chronic intake of an excessive amount of alcohol is currently ascertained by
      determining the concentration of direct alcohol metabolites in the hair samples
      of the alleged abusers, including ethyl glucuronide (EtG) and, less frequently,
      fatty acid ethyl esters (FAEEs). Indirect blood biomarkers of alcohol abuse are
      still determined to support hair EtG results and diagnose a consequent liver
      impairment. In the present study, the supporting role of hair FAEEs is compared
      with indirect blood biomarkers with respect to the contexts in which hair EtG
      interpretation is uncertain. Receiver Operating Characteristics (ROC) curves and
      multivariate Principal Component Analysis (PCA) demonstrated much stronger
      correlation of EtG results with FAEEs than with any single indirect biomarker or
      their combinations. Partial Least Squares Discriminant Analysis (PLS-DA) models
      based on hair EtG and FAEEs were developed to maximize the biomarkers information
      content on a multivariate background. The final PLS-DA model yielded 100% correct
      classification on a training/evaluation dataset of 155 subjects, including both
      chronic alcohol abusers and social drinkers. Then, the PLS-DA model was validated
      on an external dataset of 81 individual providing optimal discrimination ability
      between chronic alcohol abusers and social drinkers, in terms of specificity and
      sensitivity. The PLS-DA scores obtained for each subject, with respect to the PLS
      DA model threshold that separates the probabilistic distributions for the two
      classes, furnished a likelihood ratio value, which in turn conveys the strength
      of the experimental data support to the classification decision, within a
      Bayesian logic. Typical boundary real cases from daily work are discussed, too.

PMID- 29174053
TI  - Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two
      photon photodynamic therapy.
AB  - The proof of concept for two-photon activated photodynamic therapy has already
      been achieved for cancer treatment but the efficiency of this approach still
      heavily relies on the availability of photosensitizers combining high two-photon
      absorption and biocompatibility. In this line we recently reported on a series of
      porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production
      quantum yield as well as high two-photon absorption cross-sections but with a
      very poor cellular internalization. We present herein new photosensitizers of the
      same porphyrin-triphenylamine hybrid series but bearing cationic charges which
      led to strongly enhanced water solubility and thus cellular penetration. In
      addition the new compounds have been found localized in mitochondria that are
      preferential target organelles for photodynamic therapy. Altogether the strongly
      improved properties of the new series combined with their specific mitochondrial
      localization lead to a significantly enhanced two-photon activated photodynamic
      therapy efficiency.

PMID- 29174054
TI  - Effect of polyphenols from coffee and grape on gene expression in myoblasts.
AB  - Coffee and grape contain various bioactive compounds like polyphenols that may
      exert beneficial effects, especially antioxidant activity, on human health upon
      consumption. However, the molecular mechanisms through which these effects are
      achieved are not fully elucidated. Thus, in the present study in order to
      investigate these mechanisms, a whole genome expression DNA microarray analysis
      was carried out in myoblasts treated with polyphenols of coffee and grape pomace
      at concentrations that improved the redox status. Grape was composed of catechin,
      epicatechin, cyanidin, malvidin, delphinidin, petunidin, myrtillin, kuromanin,
      oenin, peonidin, quercetin, gallic acid and caftaric acid as LC-MS revealed, with
      a total polyphenolic content (TPC) of 648 mg of gallic acid equivalents/g of dry
      matter. Coffee had a TPC of 42.61 mg GAE/g coffee and was composed of 3
      chlorogenic acid (16.61 mg/g), 4- and 5-chlorogenic acids (13.62 mg/g), as UHPLC
      HRMS revealed. According to the results, grape polyphenols altered mainly the
      expression of cytoskeleton and differentiation-associated genes, while coffee
      compounds had a more profound effect, on the expression levels of many metabolic
      and antioxidant genes possibly through the nuclear factor (erythroid-derived 2)
      like-2 (Nrf2) pathway.

PMID- 29174055
TI  - Regression equations for the estimation of stature and body mass using a Greek
      documented skeletal collection.
AB  - Body size is an important variable in bioarchaeological and forensic studies,
      making the accurate calculation of stature and body mass imperative. Given that
      anatomical and morphometric approaches offer accurate results but require a
      particularly good preservation of the skeletal material, whereas mathematical and
      mechanical methods are more easily applicable but they are largely population
      specific, the present paper uses a 'hybrid' approach in order to generate
      regression equations for the prediction of stature and body mass in a modern
      Greek sample. Specifically, anatomical and morphometric methods were used to
      calculate the stature and body mass of the individuals and regression equations
      using the Ordinary Least Squares and Reduced Major Axis methods were generated
      with long bone lengths and femoral head breadth as predictors. The obtained
      equations exhibit low random and directional error and perform better than
      existing equations designed using different samples from the United States,
      Europe, and the Balkans. Therefore, these equations are more appropriate for
      modern Greek material.

PMID- 29174056
TI  - Impact of the time interval from completion of neoadjuvant chemotherapy to
      initiation of postoperative adjuvant chemotherapy on the survival of patients
      with advanced ovarian cancer.
AB  - OBJECTIVE: To investigate the relationship of the time interval from the
      completion of neoadjuvant chemotherapy (NAC) to the initiation of postoperative
      adjuvant chemotherapy (POAC) with the survival outcomes in patients with ovarian
      cancer. METHODS: We retrospectively investigated 220 patients with pathologically
      confirmed epithelial ovarian cancer who received NAC at Yonsei Cancer Hospital
      between 2006 and 2016. The time interval was defined as the period from the
      completion of NAC, spanning interval debulking surgery (IDS), to the initiation
      of POAC. RESULTS: The median time interval was 42 (range 16-178) days; 103
      patients (53.1%) received POAC within 42days after NAC while 91 patients (46.9%)
      received it after 42days. There were no significant differences in patient
      characteristics between these 2 groups. Kaplan-Meier analysis showed that
      patients with longer time intervals (>42days) had poorer progression-free
      survival and overall survival (P=0.039 and 0.005, respectively). In the
      multivariate analysis, patients with longer time intervals had significantly
      poorer progression-free (hazard ratio, 1.41; 95% confidence interval, 0.98-2.03;
      not significant) and overall survivals (hazard ratio, 2.03; 95% confidence
      interval, 1.16-3.54). When the patients were categorized according to time
      interval quartiles (<=37, 38-42, 43-50, and >50days), longer time intervals were
      associated with higher risks of recurrence and death (P for trend: 0.006 and
      <0.001, respectively). CONCLUSION: The time interval from the completion of NAC
      to the initiation of POAC appears to influence survival. Efforts to reduce the
      time interval might improve the outcomes in ovarian cancer patients undergoing
      NAC.

PMID- 29174057
TI  - Curbing opioid requirements after inguinal hernia repair.

PMID- 29174058
TI  - Intraoperative parathormone spikes during parathyroidectomy may be associated
      with multiglandular disease.
AB  - BACKGROUND: The importance of intraoperative parathormone "spikes" during
      parathyroidectomy remains unclear. This study compared patients with and without
      intraoperative parathormone spikes during parathyroidectomy using the criterion
      of a > 50% parathormone and determined the effect of intraoperative parathormone
      spikes on operative outcome. METHODS: We performed a retrospective review of
      prospectively collected data on 683 patients who underwent parathyroidectomy
      guided by intraoperative parathormone monitoring. An intraoperative parathormone
      "spike value" was calculated by subtracting the preincision intraoperative
      parathormone value from the pre-excision intraoperative parathormone value (SV =
      PE - PI). An intraoperative parathormone spike was defined as having a positive
      spike value >=9 pg/mL (>=10th percentile of all spike values). RESULTS: Of 683
      patients, 224 (33%) had intraoperative parathormone spikes and a greater rate of
      multiglandular disease (8% vs. 3%, P < 0.05) and bilateral neck exploration (10%
      vs. 5%, P < 0.05) compared with patients without intraoperative parathormone
      spikes. Overall, there were no differences between parathyroidectomy patients
      with and without intraoperative parathormone spikes in terms of operative success
      (98.2% vs. 98.0%), failure (1.8% vs. 2.0%), or recurrence rates (0.4% vs. 1.3%).
      CONCLUSIONS: Although the presence of intraoperative parathormone spikes may
      increase suspicion for multiglandular disease, the ability of intraoperative
      parathormone monitoring to predict operative success after parathyroidectomy is
      not affected by spikes.

PMID- 29174059
TI  - Vibratory movements in contests between females of the feather-legged spider
      (Uloborus plumipes).
AB  - Females of the feather-legged spider Uloborus plumipes invade, and compete for,
      each other's orb webs. In the context of these competitive interactions the
      question arose how the spiders communicate. Since substrate-borne vibrations are
      the most important component of the sensory environment of web-building spiders,
      we investigated vibratory movements that might serve as signals of communication.
      Three behaviors were found to be associated with female-female contests and to
      cause propagating vibrations in the spider webs: thread pulling, abdominal
      trembling, and web shaking. While thread pulling and abdominal trembling were
      also observed when prey insects were caught in the webs, web shaking occurred
      only in response to the presence of a competing conspecific. Caused by flexing of
      the first legs and a vigorous rotary movement of the opisthosoma, web shaking
      creates a short burst of strong oscillations of the orb web. This behavior always
      elicited a behavioral reaction by the competitor and may serve as an
      intraspecific signal in the mutual assessment of competing spiders. We suggest
      that web shaking communicates resource holding potential in U. plumipes.

PMID- 29174060
TI  - Feasibility of a 6-Month Yoga Program to Improve the Physical and Psychosocial
      Status of Persons with Multiple Sclerosis and their Family Members.
AB  - CONTEXT: To the best of our knowledge, there has been no study on yoga that
      includes both persons with multiple sclerosis (MS) and their family members.
      Because yoga has therapeutic effects in both persons with MS and healthy persons,
      we hypothesized that it would be an effective method to improve not only the
      physical and psychosocial status but also the time persons with MS and their
      family members spend together. OBJECTIVE: To examine the feasibility of a 6-month
      (long-term) yoga program to improve the physical and psychosocial status of
      persons with MS and their family members. DESIGN: Uncontrolled clinical trial.
      SETTING: The protocol was developed at the Department of Neurology, Faculty of
      Medicine, and School of Physical Therapy and Rehabilitation, Dokuz Eylul
      University, Izmir, Turkey. PARTICIPANTS: Persons with MS and healthy family
      members. MAIN OUTCOME MEASURES: Walking, balance, fatigue, health-related quality
      of life, depression, pain, and kinesiophobia. INTERVENTIONS: Yoga training was
      given once a week (at least 1h) for 6 months. The same assessors who assessed at
      baseline also performed the same assessments immediately after the end of the
      training (i.e., after 6 months). RESULTS: In total, 44 participants (27 persons
      with MS and 17 healthy family members) participated in the study. Twelve persons
      with MS and three healthy family members completed the 6-month yoga intervention.
      The completion rate for persons with MS and healthy subjects was 44.4% and 17.6%,
      respectively. In persons with MS, the mental dimension of health-related quality
      of life, walking speed, fatigue, and depression levels significantly improved
      after the yoga program (p < .05). However, there was no significant change in the
      self-reported walking impact, balance, pain, physical dimension of health-related
      quality of life, and kinesiophobia levels in the persons with MS (p > .05). This
      study suggests that a 6-month yoga program can improve the mental dimension of
      health-related quality of life, walking speed, fatigue, and depression in the
      persons with MS. However, the 6-month yoga program does not appear to be a
      feasible method to increase the time that persons with MS spend together with
      their family members.

PMID- 29174062
TI  - Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of
      T2 Phenotype.
AB  - BACKGROUND: Adding tiotropium to existing inhaled corticosteroid (ICS)
      maintenance therapy with or without a long-acting beta2-agonist (LABA) has been
      shown to be beneficial in patients with symptomatic asthma. OBJECTIVE: To assess
      whether responses to tiotropium Respimat add-on therapy were influenced by
      patients' T2 status. METHODS: In this exploratory study, data from 4 phase III
      trials were analyzed: once-daily tiotropium 5 MUg or placebo as add-on to ICS +
      LABA (PrimoTinA-asthma; 2 replicate trials; NCT00772538/NCT00776984; n = 912);
      once-daily tiotropium 5 MUg or 2.5 MUg, twice-daily salmeterol 50 MUg, or placebo
      as add-on to ICS (MezzoTinA-asthma; 2 replicate trials; NCT01172808/NCT01172821;
      n = 2100). The prespecified efficacy outcomes of these studies have been reported
      previously. Here, further exploratory subgroup analyses were performed to study
      whether these coprimary end points were influenced by serum IgE levels, blood
      eosinophil counts, and clinician judgment of allergic asthma. In addition, for
      the continuous parameters, namely, IgE and blood eosinophils, their influence on
      the treatment effect was modeled over the whole range of values. RESULTS:
      Tiotropium was efficacious in improving peak FEV1 within 3 hours postdose and
      trough FEV1, independent of T2 status. Tiotropium significantly reduced the risk
      of severe asthma exacerbations and asthma worsening, independent of T2 phenotype;
      Cox regression modeling supported a beneficial effect of tiotropium on
      exacerbations, independent of IgE levels or eosinophil counts. Numerical
      improvements in the 7-question Asthma Control Questionnaire (ACQ-7) responder
      rate with tiotropium versus placebo were observed in T2high and T2low patients;
      logistic regression modeling provided further evidence for improvement in ACQ-7
      responder rates with tiotropium, independent of IgE levels or eosinophil counts.
      CONCLUSIONS: The results of our exploratory analyses suggest that the
      improvements seen with tiotropium Respimat as add-on to ICS +/- LABA in patients
      with symptomatic asthma on lung function, exacerbation risk, and symptom control
      are independent of T2 phenotype.

PMID- 29174061
TI  - Pathobiological expression of the brain-derived neurotrophic factor (BDNF) in
      cerebellar cortex of sudden fetal and infant death victims.
AB  - Brain-derived neurotrophic factor (BDNF), a neurotrophin of the central nervous
      system, is able to regulate neuronal differentiation and modulate synaptic
      plasticity, being particularly involved in the development of the cerebellar
      cortical structure. The main aim of this study was to delineate, by
      immunohistochemistry, the BDNF expression in human cerebellar cortex of victims
      of fetal and infant death. The study was performed on a total of 45 cases, aged
      between 25 gestational weeks and 6 postnatal months, including 29 victims of
      sudden fetal and infant death and 16 age-matched subjects who died of known
      causes (Controls). We observed, in sudden death groups compared with Controls, a
      significantly higher incidence of defective BDNF expression in granule layers of
      the cerebellar cortex, which was particularly evident in the posterior lobule, a
      region that participates in respiratory control. These results were related to
      maternal smoking, allowing to speculate that nicotine, in addition to the well
      known damages, can exert adverse effects during cerebellar cortex development, in
      particular in hindering the BDNF expression in the posterior lobule. This implies
      modifications of synaptic transmission in the respiratory circuits, with obvious
      deleterious consequences on survival.

PMID- 29174063
TI  - Health Care Resource Utilization and Costs Among Adults with Atopic Dermatitis in
      the United States: A Claims-Based Analysis.
AB  - BACKGROUND: Data on health care resource utilization (HCRU) and costs for
      patients with atopic dermatitis (AD) are lacking. OBJECTIVE: The objective of
      this study was to determine HCRU and costs associated with AD in US adults.
      METHODS: This retrospective study identified patients with AD from the Truven
      Health Marketscan Commercial Claims and Encounters database during 2013 based on
      >=2 claims with International Classification of Diseases, Ninth Revision code
      691.8 (n = 10,533; first claim = index event); 1-year continuous enrollment
      before and after index was required. Patients were age- and gender-matched in a
      1:3 ratio to controls without AD (n = 31,599). Patients with AD were further
      categorized into 2 groups, with treatment regimens as surrogates for increasing
      disease severity: claim for phototherapy or systemic immunomodulatory agents
      (more severe) or no claim for either (less severe). Incremental differences in
      resource use and costs were evaluated using multivariate analysis. RESULTS: AD
      was associated with higher utilization and costs across resource categories (all
      P < .0001); adjusted total incremental annual costs were $3,302. Resource
      utilization and costs were higher in the more severe group, with adjusted total
      incremental annual costs of $4,463. CONCLUSION: AD is associated with significant
      incremental health care utilization and costs, which are higher in patients with
      more severe disease.

PMID- 29174064
TI  - The health economics of ankle and foot sprains and fractures: A systematic review
      of English-language published papers. Part 2: The direct and indirect costs of
      injury.
AB  - BACKGROUND: Ankle and foot sprains and fractures are prevalent injuries, which
      may result in substantial physical and economic consequences for the patient and
      place a financial burden on the health care system. Therefore, the objectives of
      this paper are to examine the direct and indirect costs of treating ankle and
      foot injuries (sprains, dislocations, fractures), as well as to provide an
      overview of the outcomes of full economic analyses of different treatment
      strategies. METHODS: A systematic review was carried out among seven databases to
      identify English language publications on the health economics of ankle and foot
      injury treatment published between 1980 and 2014. The direct and indirect costs
      were abstracted by two independent reviewers. All costs were adjusted for
      inflation and reported in 2016 US dollars (USD). RESULTS: Among 2047 identified
      studies, 32 were selected for analysis. The direct costs of ankle sprain
      management ranged from $292 to $2268 per patient (2016 USD), depending on the
      injury severity and treatment strategy. The direct costs of managing ankle
      fractures were higher ($1908-$19,555). Foot fracture treatment had similar direct
      costs ranging from $998 to $21,801. The economic evaluations were conducted from
      the societal or payer's perspectives. CONCLUSION: The costs of treating ankle and
      foot sprains and fractures varied among the studies, mostly due to differences in
      injury type and study characteristics, which impacted the ability of directly
      comparing the financial burden of treatment. Nonetheless, the review showed that
      the costs experienced by the patient and the health care system increased with
      injury complexity.

PMID- 29174065
TI  - Critique of inaccurate reporting in Edlavitch article on "Publishing negative
      findings and the challenge of avoiding type II errors in studies of suspect
      teratogens: Example of a recent ondansetron publication".

PMID- 29174066
TI  - A flexible control system designed for lab-scale simulations and optimization of
      composting processes.
AB  - Understanding and optimization of composting processes can benefit from the use
      of controlled simulators of various scales. The Agricultural Research
      Organization Composting Simulator (ARO-CS) was recently built and it is flexibly
      automated by means of a programmable logic controller (PLC). Temperature, carbon
      dioxide, oxygen and airflow are monitored and controlled in seven 9-l reactors
      that are mounted into separate 80-l water baths. The PLC program includes three
      basic heating modes (pre-determined temperature profile, temperature-feedback
      ("self-heating"), and carbon dioxide-dependent temperature), three basic aeration
      modes (airflow dependence on temperature, carbon dioxide, or oxygen) and enables
      all possible combinations among them. This unique high flexibility provides a
      robust and valuable research tool to explore a wide range of research questions
      related to the science and engineering of composting. In this article the logic
      and flexibility of the control system is presented and demonstrated and its
      potential applications are discussed.

PMID- 29174067
TI  - Recycled concrete aggregate as road base: Leaching constituents and
      neutralization by soil Interactions and dilution.
AB  - Recycled Concrete Aggregate (RCA) is often used as a replacement for natural
      aggregate in road construction activities because of its excellent mechanical
      properties, and this trend should increase as more transportation departments
      include RCA in specifications and design manuals. Concerns raised by some
      engineers and contractors include impacts from leachate generated by RCA, both
      from transport of metals to water sources and the impact of a high pH leachate on
      corrosion of underlying metal drainage pipes. In this study, RCA collected from
      various regions of Florida exhibited pH ranging from 10.5 to 12.3. Concentrations
      of Al, Ba, Cr, Fe, Mo, Na, Ni, Sb, and Sr measured using batch leaching tests
      exceeded applicable risk-based thresholds on at least some occasions, but the
      concentrations measured suggest that risk to water supplies should be controlled
      because of dilution and attenuation. Two mechanisms of pH neutralization were
      evaluated. Soil acidity plays a role, but laboratory testing and chemical
      modeling found that at higher liquid-to-solid ratios the acidity is exhausted. If
      high pH leachate did reach groundwater, chemical modeling indicated that
      groundwater dilution and carbonation would mitigate groundwater pH effects.

PMID- 29174068
TI  - [The impact of therapeutic inertia and the degree of the medication adherence on
      the control goals for patients with diabetes].
AB  - OBJECTIVE: The purpose of this study was to analyse both the impact of low
      therapeutic adherence (TA) and therapeutic inertia (TI) on poor blood glucose
      control and on risk factors for heart disease in patients with DM2. MATERIAL AND
      METHODS: A cross-sectional study was conducted in a Primary Halth Care centre. A
      total of 320 patients with DM2 were included and an assessment was made of
      control goals (HbA1c<=7%, blood pressure <=130/80mmHg, and LDL
      cholesterol<=100mg/dl). A pharmacy retrieval <80% was considered as a lack of TA
      and the non-modification of treatment in badly controlled patient as TI. RESULTS:
      The percentage of patients with good control of HbA1c, blood pressure and LDL
      cholesterol was 62.5%, 40.9%, and 35.9%, respectively. Lower figures of TA were
      present in poorly controlled patients, and TI was not found to be related to TA.
      In the patients with poor HbA1c control, 25.8% had TI, 24.8% poor TA, and 11.9%
      had both of them. As regards LDL-cholesterol, 3.6% presented poor TA, 70.4%
      showed TI, and 16% with poor TA and TI (P<.001). As for blood pressure, 3.5% of
      patients had poor TA, 54.6% had TI, and 21.5% of them had poor TA as well as TI
      (P<.01). CONCLUSIONS: Lack of therapeutic adherence and therapeutic inertia were
      found in a high percentage of poorly-controlled DM2 patients with bad control.
      Therapeutic inertia was found to be of great relevance in this study.

PMID- 29174069
TI  - [Risk of acute hypocalcaemia in a patient after total thyroidectomy and during
      endurance exercise: A case report].

PMID- 29174071
TI  - Exchange transfusions for extreme hypertriglyceridemia in a 7-week-old infant
      with multi-organ failure.
AB  - Severe hypertriglyceridemia is the third most common cause of acute pancreatitis
      and is strongly associated with an increased risk of cardiovascular disease. In
      infants, the most common cause of severe hypertriglyceridemia is lipoprotein
      lipase deficiency. We describe a 7-week-old infant with severe
      hypertriglyceridemia, who presented with frequent gastrointestinal bleeding,
      respiratory distress, a decreased level of consciousness and lipemia retinalis.
      Triglycerides were reduced from 734 to 2 mmol/L (64,956-177 mg/dL), by exchange
      transfusions. The infant made a remarkable recovery with no sequelae. This case
      highlights atypical, protean presentations and a potential treatment when
      established therapies are unavailable.

PMID- 29174070
TI  - ACS NSQIP risk calculator reliability in head and neck oncology: The effect of
      prior chemoradiation on NSQIP risk estimates following laryngectomy.
AB  - PURPOSE: To determine whether inclusion of chemoradiation history increases
      estimated risk for complications following total laryngectomy using the American
      College of Surgeons National Surgical Quality Improvement Program (NSQIP)
      Surgical Risk Calculator. MATERIALS AND METHODS: A retrospective review of 96
      patients with laryngeal cancer, approximately half of who had received prior
      chemoradiation, who underwent laryngectomy between January 2010 and December
      2014. NSQIP estimates were calculated and compared to actual event occurrence
      using receiver operating characteristic (ROC) curves, Brier scores, and risk
      estimates. RESULTS: Patients who had received prior chemoradiation were at
      significantly greater risk for complication postoperatively (OR=2.63, 95%
      CI=1.145-6.043). NSQIP Calculator discriminability and accuracy were generally
      poor for this sample. While NSQIP estimates significantly predicted risk for any
      postoperative complication, pneumonia, and discharge to nursing care for primary
      laryngectomy patients, predictive capability was lost among salvage laryngectomy
      patients. NSQIP adjustments to both Somewhat Higher and Significantly Higher Risk
      categories did not improve predictive capability. Of the risk factors considered
      by NSQIP, preoperative functional status (p=0.041), age at time of surgery
      (p<0.008), and inclusion of neck dissection (p=0.035) emerged as significant
      predictors of actual postoperative complications, though again estimates lost
      significance among salvage laryngectomy patients. CONCLUSIONS: The NSQIP
      Calculator may be poorly calibrated to estimate postoperative complication risk
      for patients previously exposed to chemoradiation undergoing salvage
      laryngectomy. Caution should be used when estimating postoperative risk among
      patients undergoing salvage procedures, especially those of older age, poorer
      functional status, and those requiring neck dissection.

PMID- 29174072
TI  - Acute myocardial infarction in a 25-year-old woman with sitosterolemia.
AB  - We report the case of acute myocardial infarction in a 25-year-old woman with
      sitosterolemia. She was treated using statins, but her low-density lipoprotein
      cholesterol (LDL-C) levels did not decrease appreciably. Genetic analysis
      revealed mutations in the ABCG8 gene. Ezetimibe treatment was initiated, and her
      LDL-C levels decreased substantially. Sitosterolemia must be considered in the
      differential diagnosis of familial hypercholesterolemia in case of early onset
      cardiovascular disease patient with high LDL-C.

PMID- 29174073
TI  - Lumbar Medial Branch Block Volume-Dependent Dispersion Patterns as a Predictor
      for Ablation Success: A Cadaveric Study.
AB  - BACKGROUND: Lumbar facet arthropathy is a common cause of low back pain.
      Literature supports treatment with radiofrequency ablation (RFA) of associated
      nerves that innervate lumbar facets when alternative conservative therapies have
      failed. Diagnostic local anesthetic blocks precede therapeutic ablation, but have
      a false-positive rate of 27%-63%, and some authors have questioned their utility
      in predicting therapeutic response to RFA. The authors of the current study
      believe that injectate volume may be a contributing factor to false positivity.
      OBJECTIVE: To evaluate the difference in volume dispersion between 0.25 mL and
      0.5 mL of injectate when performing lumbar medial branch blocks. We hypothesized
      that injection volumes greater than 0.25 mL during lumbar medial branch blocks
      would affect the distal branches of the adjacent medial branches, thus decreasing
      the specificity of the procedure. Thus, we attempted to demonstrate that
      injection volumes greater than 0.25 mL during lumbar medial branch blocks would
      affect the distal branches of the adjacent medial branches, which might increase
      false positivity of the blocks. STUDY DESIGN: Cadaveric investigation. SETTING:
      Tertiary care center. PARTICIPANTS: Not applicable. OUTCOME MEASUREMENTS: To
      demonstrate that the spread of lumbar medial branch blocks using commonly
      injected volume coats adjacent structures that are not affected by radiofrequency
      ablation. METHODS: Six cadavers were chosen with nondissected lumbar spines.
      Fluoroscopically guided medial branch injections were performed bilaterally using
      the posterior oblique approach. A volume of 0.25 mL or 0.50 mL of a 9:1 solution
      of Omnipaque 240 and 1% medical grade methylene blue were delivered to the left
      and right sides, respectively. Postinjection computed tomographic imaging was
      performed, followed by dissection. RESULTS: Both volumes adequately coated the
      medial branches, but in the 0.5-mL injectate cohort there was consistent spread
      dorsally to the superficial muscles and distal segments of the dorsal branches
      distant to the target nerves, whereas in the 0.25-mL injectate cohort the spread
      was contained in the deep and intermediate muscular lumbar layers, close to the
      intended target. CONCLUSION: We suggest that a 0.5-mL injectate volume in
      clinical practice may produce an adjacent-level nerve block in addition to the
      intended injection level, thus decreasing the specificity of a targeted lumbar
      medial branch block. A 0.25-mL quantity of injectate reliably contacted the
      lumbar medial branches without extensive extravasation. Presumably, this means
      that 0.25 mL total volume for a lumbar medial branch block may provide greater
      specificity for RFA planning. LEVEL OF EVIDENCE: NA.

PMID- 29174074
TI  - Sister Elizabeth Kenny and Polio in America: Doyenne or Demagogue in Her Role in
      Rehabilitation Medicine?

PMID- 29174075
TI  - Medication non-adherence in the context of situated uncertainty: Moving beyond
      simple, dichotomous approaches.

PMID- 29174076
TI  - Characteristics and Progression of Hearing Loss in Children with Down Syndrome.
AB  - OBJECTIVES: To evaluate hearing impairment in children with Down syndrome, and to
      describe the factors that influence the severity of hearing loss or changes in
      hearing over time. STUDY DESIGN: Using the Audiological and Genetic Database
      (AudGenDB), audiograms of children with Down syndrome were analyzed
      retrospectively for type, severity, and laterality of hearing loss, as well as
      changes over time. Medical charts and imaging results were reviewed to identify
      factors influencing hearing loss. RESULTS: Among the 1088 patients with Down
      syndrome included in the study, 921 had hearing loss in at least 1 ear, 91.1% had
      bilateral hearing loss, and 8.9% had unilateral hearing loss (1760 total ears
      with hearing loss). Of the ears with hearing loss, 18.8% (n = 180) had moderate
      or worse hearing loss. "Undefined" hearing loss and pure conductive hearing loss
      (CHL) were the most common types, followed by mixed hearing loss and
      sensorineural hearing loss (SNHL). Three-quarters (75.4%) of the children had
      experienced chronic otitis media or more than 2 episodes of acute otitis media.
      Patients with bilateral, mixed hearing loss or a history of seizures were at risk
      for more severe hearing loss. CHL, absence of cholesteatoma, and placement of
      first ear tubes before age 2 years were associated with greater improvement in
      hearing over time, whereas SNHL and mixed hearing loss were associated with
      progressive decline. CONCLUSION: Children with Down syndrome who have bilateral,
      mixed hearing loss or a history of seizures are at risk for more severe hearing
      loss. SNHL and mixed hearing loss should not be overlooked in patients with CHL.
      All patients with Down syndrome will benefit from serial audiograms, especially
      those children with SNHL or mixed hearing loss, which is likely to worsen over
      time.

PMID- 29174077
TI  - Occipital Dermal Sinus Tract.

PMID- 29174078
TI  - Acute Pancreatitis Admission Trends: A National Estimate through the Kids'
      Inpatient Database.
AB  - OBJECTIVES: To evaluate national health care use and costs for pediatric acute
      pancreatitis. STUDY DESIGN: The Kids' Inpatient Database for 2006, 2009, and 2012
      was queried for patients with a principal diagnosis of acute pancreatitis. Cases
      were grouped by age: preschool (<5 years of age), school age (5-14 years of age),
      and adolescents (>14 years of age). RESULTS: A total of 27 983 discharges for
      acute pancreatitis were found. The number of admissions increased with age: young
      n = 1279, middle n = 8012, and older n = 18 692. Duration of stay was highest in
      preschool children (median, 3.47 days; IQR, 2.01-7.35), compared with school age
      (median, 3.22 days; IQR, 1.81-5.63) and adolescents (median, 2.87 days; IQR, 1.61
      4.81; P < .001). The median cost of hospitalization varied with age: $6726 for
      preschoolers, $5400 for school-aged children, and $5889 for adolescents (P <
      .001). Acute pancreatitis-associated diagnoses varied by age. The presence of
      gallstone pancreatitis, alcohol, and hypertriglyceridemia was more common among
      older children compared with younger children (P < .001). There was an increasing
      trend in acute pancreatitis, chronic pancreatitis, and obesity for the 2 older
      age groups (P < .001). CONCLUSION: Admission of children for acute pancreatitis
      constitutes a significant healthcare burden, with a rising number of admissions
      with age. However, the cost and duration of stay per admission are highest in
      young children.

PMID- 29174079
TI  - Laryngeal Mask Airway for Surfactant Administration in Neonates: A Randomized,
      Controlled Trial.
AB  - OBJECTIVE: To determine if preterm infants with moderate respiratory distress
      syndrome on continuous positive airway pressure (CPAP) who received surfactant
      via a laryngeal mask airway (LMA) would have a decreased rate of intubation and
      mechanical ventilation compared with those on CPAP who did not receive
      surfactant. STUDY DESIGN: In this prospective, multicenter, randomized controlled
      trial, 103 premature infants 280/7-356/7 weeks gestation, >=1250 g and <=36 hours
      old on CPAP requiring fraction of inspired oxygen 0.30-0.40 were assigned to
      receive surfactant administered through an LMA then placed back on CPAP (LMA
      group) or maintained on CPAP with no surfactant administered (control group). The
      primary outcome was treatment failure necessitating intubation and mechanical
      ventilation in the first 7 days of life. RESULTS: Surfactant administration
      through an LMA (n = 50) significantly decreased the rate of intubation and
      mechanical ventilation compared with controls (n = 53): 38% vs 64%, respectively,
      OR 0.30 (95% CI 0.13, 0.70), P = .006, number needed to treat: 4). There were no
      serious adverse events associated with placement of the LMA or surfactant
      administration. CONCLUSIONS: In premature neonates with moderate respiratory
      distress syndrome, surfactant administered through an LMA decreased the rate of
      intubation and mechanical ventilation. This intervention may have significant
      impact on clinical care in both high and low resource settings. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01116921.

PMID- 29174080
TI  - Patterns of Care at the End of Life for Children and Young Adults with Life
      Threatening Complex Chronic Conditions.
AB  - OBJECTIVE: To characterize patterns of care at the end of life for children and
      young adults with life-threatening complex chronic conditions (LT-CCCs) and to
      compare them by LT-CCC type. STUDY DESIGN: Cross-sectional survey of bereaved
      parents (n = 114; response rate of 54%) of children with noncancer, noncardiac LT
      CCCs who received care at a quaternary care children's hospital and medical
      record abstraction. RESULTS: The majority of children with LT-CCCs died in the
      hospital (62.7%) with more than one-half (53.3%) dying in the intensive care
      unit. Those with static encephalopathy (AOR, 0.19; 95% CI, 0.04-0.98), congenital
      and chromosomal disorders (AOR, 0.28; 95% CI, 0.09-0.91), and pulmonary disorders
      (AOR, 0.08; 95% CI, 0.01-0.77) were significantly less likely to die at home
      compared with those with progressive central nervous system (CNS) disorders.
      Almost 50% of patients died after withdrawal or withholding of life-sustaining
      therapies, 17.5% died during active resuscitation, and 36% died while receiving
      comfort care only. The mode of death varied widely across LT-CCCs, with no
      patients with pulmonary disorders dying receiving comfort care only compared with
      66.7% of those with CNS progressive disorders. A majority of patients had
      palliative care involvement (79.3%); however, in multivariable analyses, there
      was distinct variation in receipt of palliative care across LT-CCCs, with
      patients having CNS static encephalopathy (AOR, 0.07; 95% CI, 0.01-0.68) and
      pulmonary disorders (AOR, 0.07; 95% CI, 0.01-.09) significantly less likely to
      have palliative care involvement than those with CNS progressive disorders.
      CONCLUSIONS: Significant differences in patterns of care at the end of life exist
      depending on LT-CCC type. Attention to these patterns is important to ensure
      equal access to palliative care and targeted improvements in end-of-life care for
      these populations.

PMID- 29174081
TI  - Tdap Vaccination Among Healthcare Personnel-21 States, 2013.
AB  - INTRODUCTION: Outbreaks of pertussis can occur in healthcare settings.
      Vaccinating healthcare personnel may be helpful in protecting healthcare
      personnel from pertussis and potentially limiting spread to others in healthcare
      settings. METHODS: Data from 21 states using the 2013 Behavioral Risk Factor
      Surveillance System industry/occupation module were analyzed in 2016. Tetanus,
      diphtheria, and acellular pertussis (Tdap) vaccination status was self-reported
      by healthcare personnel along with their occupation, healthcare setting/industry,
      demographics, and access to care factors. To compare groups, t-tests were used.
      The median state response rate was 44.0%. RESULTS: Among all healthcare
      personnel, 47.2% were vaccinated for Tdap. Physicians had higher Tdap coverage
      (66.8%) compared with all other healthcare personnel except nurse practitioners
      and registered nurses (59.5%), whose coverage did not statistically differ from
      that of physicians. Tdap vaccination coverage was higher among workers in
      hospitals (53.3%) than in long-term care facilities (33.3%) and other clinical
      settings, such as dentist, chiropractor, and optometrist offices (39.3%).
      Healthcare personnel who were younger, who had higher education, higher annual
      household income, a personal healthcare provider, and health insurance had higher
      Tdap vaccination coverage compared with reference groups. Tdap vaccination
      coverage among healthcare personnel in 21 states ranged from 30.6% in Mississippi
      to 65.9% in Washington. CONCLUSIONS: Improvement in Tdap vaccination among
      healthcare personnel is needed to potentially reduce opportunities for spread of
      pertussis in healthcare settings. On-site workplace vaccination, offering
      vaccines free of charge, and promoting vaccination may increase vaccination among
      healthcare personnel.

PMID- 29174082
TI  - Multiple reaction monitoring mass spectrometry to identify novel plasma protein
      biomarkers of treatment response in cystic fibrosis pulmonary exacerbations.
AB  - BACKGROUND: Systemic inflammation decreases with IV antibiotics during the
      treatment of CF pulmonary exacerbations (PEx). We used multiple reaction
      monitoring mass spectrometry and immunoassays to monitor blood proteins during
      PEx treatment to determine if early changes could be used to predict PEx outcomes
      following treatment. METHODS: Blood samples from 25 PEx (22 unique adults) were
      collected within 24h of admission, day 5, day 10, and at IV antibiotic
      completion. Ninety-two blood proteins involved in host immunity and inflammation
      were measured. RESULTS: Levels of several blood proteins changed from admission
      to end of IV antibiotics, most increasing with treatment. Early changes
      (admission to day 5) in fibrinogen levels had the strongest correlation with
      overall improvement in CFRSD-CRISS and FEV1% predicted by the end of treatment.
      CONCLUSIONS: Several plasma proteins changed significantly with IV antibiotics.
      Future studies will evaluate fibrinogen as an early biomarker of PEx treatment
      response in CF.

PMID- 29174083
TI  - Addition of an EGFP-tag to the N-terminal of influenza virus M1 protein impairs
      its ability to accumulate in ND10.
AB  - A previous report demonstrated that influenza virus infection induces
      accumulation of EGFP-tagged M1 protein (EGFP-M1) in the sub-nuclear domain ND10.
      Here, we show that the transfection of four viral protein (NP, PB2, PB1, PA)
      expression vectors and eight RNA segment expression vectors induced the formation
      of nuclear dots of EGFP-M1 as seen in virus infections. Omission of the segment 7
      RNA expression vector, however, abolished the nuclear dots of EGFP-M1. This
      result suggests an essential role for authentic M1 protein and/or M2 protein,
      both of which are encoded in segment 7, in the formation of nuclear dots of EGFP
      M1. Co-expression of M1 protein but not M2 protein with EGFP-M1 induced the
      formation of nuclear dots of EGFP-M1. The dots co-localized with PML protein,
      which is an indicator of ND10. When only M1 protein was expressed, immunostaining
      of M1 protein clearly revealed the nuclear dots and their colocalization with PML
      protein. These results demonstrate that the accumulation in ND10 is an intrinsic
      characteristic of M1 protein and EGFP addition abolishes this characteristic. The
      addition of EGFP to M1 protein induced a defect in M1 protein.

PMID- 29174085
TI  - Resistance to first-line ART and a role for dolutegravir.

PMID- 29174086
TI  - Utility of Liquid Biopsy by Improved PNA-LNA PCR Clamp Method for Detecting EGFR
      Mutation at Initial Diagnosis of Non-Small-Cell Lung Cancer: Observational Study
      of 190 Consecutive Cases in Clinical Practice.
AB  - BACKGROUND: The clinical benefit of liquid biopsy for unselected patients at
      initial diagnosis has thus far been unclear. We aimed to evaluate the utility of
      liquid biopsy at initial diagnosis, as well as the efficacy of epidermal growth
      factor receptor-tyrosine kinase inhibitor (EGFR-TKI) based on liquid biopsy
      results in clinical practice, using the improved peptide nucleic acid-locked
      nucleic acid (PNA-LNA) PCR clamp method. PATIENTS AND METHODS: We routinely
      performed liquid biopsy using the improved PNA-LNA PCR clamp method for all
      patients diagnosed with non-small-cell lung cancer (NSCLC) between June 2015 and
      October 2016. We retrospectively evaluated the reliability of liquid biopsy based
      either on clinical stage or between sensitizing EGFR mutation and T790M mutation,
      and the clinical benefit of EGFR-TKI based on the liquid biopsy results in
      practice. RESULTS: A total of 244 patients underwent liquid biopsies, with 168
      patients tested at diagnosis and 22 tested for T790M after pretreatment of EGFR
      TKI. For detecting a sensitizing EGFR mutation, the sensitivity, specificity,
      positive predictive value, and negative predictive value were 72.7%, 100%, 100%,
      and 93.7% in the group with advanced-stage NSCLC and 0, 100%, not evaluable, and
      70.5% in the group with early-stage NSCLC. The positive predictive value and
      negative predictive value for T790M were 33.3% and 55.6%, respectively. Fourteen
      patients in the liquid-positive group and 16 patients in the tissue-positive
      group received EGFR-TKI. The objective response rates of first- and second
      generation EGFR-TKI for the liquid-positive and tissue-positive groups were 90.0%
      and 90.9%, respectively. There was no significant difference in median
      progression-free survival between the liquid-positive and tissue-positive groups
      (P = .839). CONCLUSION: Patients with early-stage NSCLC should not be candidates
      for this liquid biopsy method. We recommend tissue biopsy as the preferred
      initial method of molecular analysis, with the exception of patients who are
      T790M positive or patients who are unable to tolerate invasive biopsy.

PMID- 29174087
TI  - Learning curve for transbronchial lung cryobiopsy in diffuse lung disease.
AB  - INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used in the
      diagnosis of diffuse lung disease (DLD), but no data have yet been published on
      the learning curve associated with this technique. AIM: To evaluate diagnostic
      yield, lung tissue sample length and area, and procedure-related complications in
      a cohort of TBLC procedures to define the learning curve and threshold for
      proficiency. METHODS: Retrospective analysis of the first 100 TBLCs performed in
      different segments of the same lobe in patients with suspected DLD. We compared
      diagnostic yield, sample length and area, and complications between consecutive
      groups of patients. RESULTS: The overall diagnostic yield for TBLC was 82%.
      Median sample length was 5.4mm (IQR, 5-6) and median area was 19.5mm2 (IQR, 13.3
      25). Pneumothorax was the most common complication (18%). On comparing the two
      groups of 50 consecutive patients, a significant difference was found for
      diagnostic yield (74% vs 90%; p=0.04), sample length (5.0mm [2.5-16] vs 6.0mm [4
      12;] p<0.01) and area (17.5mm2 [6-42] vs 21.5mm2 [10-49]; p<0.01). Logarithm
      regression was applied to median diagnostic yield and sample length and area for
      groups of 10 consecutive patients to define the learning curve, which plateaued
      after approximately 70 procedures. CONCLUSIONS: Our findings suggest that
      proficiency in TBLC is achieved at approximately the 70th procedure; however they
      need to be validated in more series and cohorts.

PMID- 29174084
TI  - Cost-effectiveness of public-health policy options in the presence of
      pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study.
AB  - BACKGROUND: There is concern over increasing prevalence of non-nucleoside reverse
      transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral
      therapy (ART) in low-income and middle-income countries. We assessed the
      effectiveness and cost-effectiveness of alternative public health responses in
      countries in sub-Saharan Africa where the prevalence of pretreatment drug
      resistance to NNRTIs is high. METHODS: The HIV Synthesis Model is an individual
      based simulation model of sexual HIV transmission, progression, and the effect of
      ART in adults, which is based on extensive published data sources and considers
      specific drugs and resistance mutations. We used this model to generate multiple
      setting scenarios mimicking those in sub-Saharan Africa and considered the
      prevalence of pretreatment NNRTI drug resistance in 2017. We then compared
      effectiveness and cost-effectiveness of alternative policy options. We took a 20
      year time horizon, used a cost effectiveness threshold of US$500 per DALY
      averted, and discounted DALYs and costs at 3% per year. FINDINGS: A transition to
      use of a dolutegravir as a first-line regimen in all new ART initiators is the
      option predicted to produce the most health benefits, resulting in a reduction of
      about 1 death per year per 100 people on ART over the next 20 years in a
      situation in which more than 10% of ART initiators have NNRTI resistance. The
      negative effect on population health of postponing the transition to dolutegravir
      increases substantially with higher prevalence of HIV drug resistance to NNRTI in
      ART initiators. Because of the reduced risk of resistance acquisition with
      dolutegravir-based regimens and reduced use of expensive second-line boosted
      protease inhibitor regimens, this policy option is also predicted to lead to a
      reduction of overall programme cost. INTERPRETATION: A future transition from
      first-line regimens containing efavirenz to regimens containing dolutegravir
      formulations in adult ART initiators is predicted to be effective and cost
      effective in low-income settings in sub-Saharan Africa at any prevalence of pre
      ART NNRTI resistance. The urgency of the transition will depend largely on the
      country-specific prevalence of NNRTI resistance. FUNDING: Bill & Melinda Gates
      Foundation, World Health Organization.

PMID- 29174088
TI  - Platelets are involved in in vitro swine granulosa cell luteinization and
      angiogenesis.
AB  - During corpus luteum formation, impressive biological events take place to
      guarantee the transition from original follicular to luteal cells and to support
      required massive angiogenesis. It has been demonstrated that these phenomena
      resemble those essential for wound healing. After ovulation, blood vessels
      release their content in the antral cavity and coagulation takes place.
      Involvement of platelets in corpus luteum growth has been hypothesized both in
      human and in rat. On this basis, using platelet lysate (PL), a blood derivative
      with a higher platelet concentration, we aimed to assess a potential involvement
      of platelets in swine granulosa cell luteinization and on new blood vessel
      growth. Our results demonstrate, for the first time in the swine, that platelets
      could be directly involved in granulosa cell physiological luteinization, since
      the treatment with PL shifted steroid production from estradiol 17beta to
      progesterone. Moreover, PL stimulated angiogenesis. Nitric oxide could be
      involved in these effects. These results are important to clarify complex
      intrafollicular molecular machinery. A better understanding of these mechanisms
      can be useful to develop more focused therapeutic strategies to contrast sow
      infertility. In addition, since the pig represents a model for translational
      studies, collected data could be of interest for human medicine because
      reproductive pathologies such as Polycystic Ovary Syndrome (PCOS) and
      endometriosis are often accompanied by platelet dysfunctions.

PMID- 29174089
TI  - Uncommon runs of homozygosity disclose homozygous missense mutations in two
      ciliopathy-related genes (SPAG17 and WDR35) in a patient with multiple brain and
      skeletal anomalies.
AB  - We describe a patient severely affected with multiple congenital anomalies,
      including brain malformations and skeletal dysplasia suggestive of
      cranioectodermal dysplasia (CED) ciliopathy, who unusually carries several
      homozygosity tracts involving homozygous missense mutations in SPAG17 (exon 8;
      c.1069G > C; p.Asp357His) and WDR35 (exon 13; c.1415G > A; p.Arg472Gln) as
      revealed by homozygosity mapping and next generation sequencing. SPAG17 is
      essential for the function and structure of motile cilia, while WDR35 belongs to
      the same intraflagellar transport (IFT) gene family whose protein products are
      part of functional IFT A and B complexes. Formerly, SPAG17 was related - through
      polymorphic variants - to an influence on individuals' height; more recently,
      Spag17-/- mice models were reported to present skeletal and bone defects, reduced
      mucociliary clearance, respiratory distress, and cerebral ventricular
      enlargement. Homozygous or compound heterozygous mutations in WDR35 have mainly
      been related to CED2 or short-rib thoracic dysplasia 7, with only three cases
      showing some brain anomalies. Given that our patient presents these clinical
      features and the close functional relationship between SPAG17 and WDR35, it is
      feasible that the combined effects from both mutations contribute to his
      phenotype. To our knowledge, this patient is the first to harbor a likely
      pathogenic homozygous mutation in both genes at the same time. Thus, the
      resulting complex phenotype of this patient illustrates the heterogeneity
      associated with ciliopathies and further expands the clinical and mutational
      spectrum of these diseases. Finally, we highlight the combined use of high
      throughput tools to diagnose and support the proper handling of this and other
      patients.

PMID- 29174090
TI  - Molecular cytogenetics characterization of seven small supernumerary marker
      chromosomes derived from chromosome 19: Genotype-phenotype correlation and review
      of the literature.
AB  - Only a few subjects carrying supernumerary marker chromosomes derived from 19
      chromosome (sSMC(19)) have been described to date and for a small portion of them
      the genic content has been defined at the molecular level. We present seven new
      different sSMCs(19) identified in eight individuals, seven of whom unrelated. The
      presence of the sSMC is associated with a clinical phenotype in five subjects,
      while the other three carriers, two of whom related, are normal. All sSMCs(19)
      have been characterized by means of conventional and molecular cytogenetics. We
      compare the sSMCs(19) carriers with a clinical phenotype to already described
      patients with gains (sSMCs or microduplications) of overlapping genomic regions
      with the aim to deepen the pathogenicity of the encountered imbalances and to
      assess the role of the involved genes on the phenotype. The present work supports
      the correlation between the gain of some chromosome 19 critical regions and
      specific phenotypes.

PMID- 29174091
TI  - Pancreatic hemi-agenesis in MEN1: A clinical report.
AB  - We first describe a patient with multiple endocrine neoplasia type 1 (MEN1) and
      dorsal pancreatic hemi-agenesis. Previously, pancreas divisum has been reported
      in MEN1. Recent data in mice have elucidated the molecular mechanisms of
      pancreatic endoderm specification. Disinhibition of hedgehog signaling appears to
      be important in how Gata4 and Gata6 variants cause pancreatic agenesis.
      Disinhibition of hedgehog signaling has also been observed in Men1 knockout
      pancreatic islets. Although we cannot exclude a spurious association between
      dorsal pancreatic hemi-agenesis and MEN1 in our patient, we argue that
      developmental abnormalities of the pancreas may have to be considered as possibly
      related to the MEN1 phenotype.

PMID- 29174093
TI  - Novel GNB1 de novo mutation in a patient with neurodevelopmental disorder and
      cutaneous mastocytosis: Clinical report and literature review.
AB  - De novo monoallelic mutations in the GNB1 gene, encoding a beta subunit of
      heterotrimeric G proteins, cause a newly recognized disorder with the typical
      clinical picture of severe developmental delay/intellectual disability, hypotonia
      and extrapyramidal symptoms. We describe another case of the condition with
      manifestations of cutaneous mastocytosis associated with a novel do novo mutation
      GNB1NM_001282539.1: c.230G > T; p.(Gly77Val). We also present the detailed
      clinical and etiopathogenetic discussion on previously diagnosed patients as well
      as suggestions for the link of the mutation with skin disease.

PMID- 29174092
TI  - Rare copy number variants identified in prune belly syndrome.
AB  - Prune belly syndrome (PBS), also known as Eagle-Barrett syndrome, is a rare
      congenital disorder characterized by absence or hypoplasia of the abdominal wall
      musculature, urinary tract anomalies, and cryptorchidism in males. The etiology
      of PBS is largely unresolved, but genetic factors are implicated given its
      recurrence in families. We examined cases of PBS to identify novel pathogenic
      copy number variants (CNVs). A total of 34 cases (30 males and 4 females) with
      PBS identified from all live births in New York State (1998-2005) were genotyped
      using Illumina HumanOmni2.5 microarrays. CNVs were prioritized if they were
      absent from in-house controls, encompassed >=10 consecutive probes, were >=20 Kb
      in size, had <=20% overlap with common variants in population reference controls,
      and had <=20% overlap with any variant previously detected in other birth defect
      phenotypes screened in our laboratory. We identified 17 candidate autosomal CNVs;
      10 cases each had one CNV and four cases each had two CNVs. The CNVs included a
      158 Kb duplication at 4q22 that overlaps the BMPR1B gene; duplications of
      different sizes carried by two cases in the intron of STIM1 gene; a 67 Kb
      duplication 202 Kb downstream of the NOG gene, and a 1.34 Mb deletion including
      the MYOCD gene. The identified rare CNVs spanned genes involved in mesodermal,
      muscle, and urinary tract development and differentiation, which might help in
      elucidating the genetic contribution to PBS. We did not have parental DNA and
      cannot identify whether these CNVs were de novo or inherited. Further research on
      these CNVs, particularly BMP signaling is warranted to elucidate the pathogenesis
      of PBS.

PMID- 29174094
TI  - Missense mutation of TTC7A mimicking tricho-hepato-enteric (SD/THE) syndrome in a
      patient with very-early onset inflammatory bowel disease.
AB  - Tricho-hepato-enteric syndrome (SD/THE) and Multiple intestinal atresia with
      combined immune deficiency (MIA-CID) are autosomal recessive disorders that
      present immunological and gastrointestinal features. There are two different
      phenotypes of patients with TTC7A mutations: the severe form, caused by null
      mutations and leading to the classical MIA-CID; and the mild form, caused by
      missense mutations and leading to predominant features of VEO-IBD, less severe
      immunological involvement and hair abnormalities. We expand the knowledge about
      TTC7A deficiency, describing a patient with the mild phenotype of TTC7A
      deficiency but presenting overlapping features of SD/THE and MIA-CID: intestinal
      atresia and inflammatory bowel disease evocative of MIA-CID, but also dental
      abnormalities, huge forehead, liver abnormalities, autoimmune thyroiditis and
      hypogammaglobulinemia, evocative of SD/THE.

PMID- 29174095
TI  - Prevention, Diagnosis, and Treatment of Implant Infection in the Distal Upper
      Extremity.
AB  - Implant related infection is relatively unusual in surgery to the hand and distal
      upper limb. When such infections occur, the consequences can be devastating. We
      review the latest guidance and research on the prevention, diagnosis, and
      management of implant-associated infections in the hand and distal upper limb.

PMID- 29174096
TI  - Surgical and Nonsurgical Management of Mallet Finger: A Systematic Review.
AB  - PURPOSE: The current literature describes multiple surgical and nonsurgical
      techniques for the management of mallet finger injuries, and there is no
      consensus on the indications for surgical treatment. The objective of this study
      was to determine, through a literature review, if any conclusions can be drawn
      concerning the indications for surgery in mallet finger injuries; the treatment
      outcomes of surgical versus nonsurgical management; the most effective methods of
      surgical and nonsurgical treatment; and the most common treatment complications
      of mallet finger injuries. METHODS: A systematic review of multiple databases was
      performed. English language clinical studies evaluating therapeutic interventions
      for mallet fingers that reported objective, standardized outcome measures were
      included. Basic science studies, cadaveric studies, conference abstracts, level V
      evidence studies, studies lacking statistical data, and tendinous injuries other
      than mallet fingers were excluded. Salvage procedures and studies evaluating
      exclusively chronic lesions were also excluded. RESULTS: Forty-four studies that
      reported clinical outcomes for the treatment of mallet finger injuries, 22
      evaluating surgical treatments and 17 studies investigating nonsurgical
      treatments were included. The average distal interphalangeal joint extensor lag
      was 5.7 degrees  after surgical treatment and 7.6 degrees  after nonsurgical
      treatment. Complication rates of surgical and nonsurgical interventions were
      comparable (14.5% and 12.8%, respectively). Five studies directly compared the
      outcomes of surgical with nonsurgical management, with mixed results and
      recommendations. CONCLUSIONS: Both surgical and nonsurgical treatments of mallet
      finger injuries lead to excellent clinical outcomes. Insufficient evidence is
      available to determine when surgical intervention is indicated. Based on our
      literature review, it appears that these treatments are equivalent and should be
      individualized to the patient. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 29174097
TI  - Effects of propofol on ventricular repolarization and incidence of malignant
      arrhythmias in adults.
AB  - BACKGROUND: Propofol is commonly used for procedural sedation in interventional
      electrophysiology. However, ventricular arrhythmias under Propofol have been
      reported. Our aim was to investigate ventricular repolarization and incidence of
      ventricular arrhythmias under Propofol infusion in adults with cardiac
      arrhythmias. METHODS: QRS, QTcB (Bazett), QTcFri (Fridericia), JTc, measurement
      of T peak to Tend time (Tp-e) at baseline and under Propofol infusion was
      performed in 235 patients. Screening for unexpected ventricular arrhythmias was
      performed in 1165 patients undergoing EP procedures under Propofol. RESULTS: A
      significant prolongation of Tp-e under Propofol infusion (79.7+/-17.3 vs. 86.4+/
      22.5ms, p<0.001) and of QTcFri (429.3+/-35.8 vs. 435.5+/-36.5, p=0.033) was
      detected. No significant change of the QTcB interval, JTc interval or QRS
      duration was observed. One case (0.09%) of ventricular fibrillation during rapid
      ventricular pacing under Propofol occurred. CONCLUSION: Although transmural
      dispersion of ventricular repolarisation is increased under Propofol, incidence
      of malignant ventricular arrhythmias is low. For evaluation of QT interval under
      Propofol, Fridericia's correction formula should be used rather than Bazett's
      formula.

PMID- 29174098
TI  - Which admission electrocardiographic parameter is more powerful predictor of no
      reflow in patients with acute anterior myocardial infarction who underwent
      primary percutaneous intervention?
AB  - BACKGROUND: Acute transmural ischemia due to left anterior descending artery
      (LAD) occlusion changes precordial R and Q wave durations owing to depressed
      intramyocardial activation. We investigated the prognostic value of sum of
      precordial Q wave duration/sum of precordial R wave duration ratio (Q/R) in
      patients with first acute anterior myocardial infarction (AAMI) treated with
      primary percutaneous coronary intervention (PPCI). METHODS: In this prospective
      analysis, we evaluated the no-reflow predictive value of Q/R on 403 patients with
      first AAMI. Patients were divided into two as no-reflow group (n=32) and control
      (n=371) group according to post-PPCI flow status. RESULTS: The patients in the no
      reflow group had significantly higher Q/R on admission electrocardiography (ECG)
      compared to patients in the control group (p<0.001). When admission ECG
      parameters were compared according to no-reflow prediction, Q/R was stronger than
      other well-accepted parameters. The best cut-off value of the Q/R to predict no
      reflow was 1.08 with 76% sensitivity and 73% specificity (AUC: 0.78; 95% CI: 0.72
      0.83; p<0.001). CONCLUSION: In patients with first AAMI treated with PPCI, Q/R in
      admission ECG may have a role as an independent predictive marker of no-reflow.

PMID- 29174099
TI  - Smartphone ECG for evaluation of ST-segment elevation myocardial infarction
      (STEMI): Design of the ST LEUIS International Multicenter Study.
AB  - In patients experiencing an ST-elevation myocardial infarction (STEMI), rapid
      diagnosis and immediate access to reperfusion therapy leads to optimal clinical
      outcomes. The rate-limiting step in STEMI diagnosis is the availability and
      performance of a 12-lead ECG. Recent technology has provided access to a reliable
      means of obtaining an ECG reading through a smartphone application (app) that
      works with an attachment providing all 12-leads of a standard ECG system. The ST
      LEUIS study was designed to validate the smartphone ECG app and its ability to
      accurately assess the presence or absence of STEMI in patients presenting with
      chest pain compared with the gold standard 12-lead ECG. We aimed to support the
      diagnostic utility of smartphone technology to provide a timely diagnosis and
      treatment of STEMI. The study will take place over 12months at five institutions.
      Approximately 60 patients will be enrolled per institution, for a total
      recruitment of 300 patients.

PMID- 29174100
TI  - Cable Bacteria Take a New Breath Using Long-Distance Electricity.
AB  - Recently, a new group of multicellular microorganisms was discovered, called
      'cable bacteria', which are capable of generating and mediating electrical
      currents across centimetre-scale distances. By transporting electrons from cell
      to cell, cable bacteria can harvest electron donors and electron acceptors that
      are widely separated in space, thus providing them with a competitive advantage
      for survival in aquatic sediments. The underlying process of long-distance
      electron transport challenges some long-held ideas about the energy metabolism of
      multicellular organisms and entails a whole new type of electrical cooperation
      between cells. This review summarizes the current knowledge about these
      intriguing multicellular bacteria.

PMID- 29174101
TI  - Antibacterial Toxins: Gram-Positive Bacteria Strike Back!
AB  - Bacteria live in communities where strains compete with each other by deploying
      an arsenal of antibacterial toxins. While the past decade revealed the vast array
      of antibacterial toxins secreted by Gram-negative bacteria, several recent
      studies have begun to uncover the ability of Gram-positive bacteria to battle
      with their own weapons.

PMID- 29174102
TI  - Corrigendum to "Craniofacial implants at a single centre 2005-2015: retrospective
      review of 451 implants" [Br J Oral Maxillofac Surg 2017;55:242-5].

PMID- 29174103
TI  - Is a fractured mandible an emergency?
AB  - We retrospectively audited the records of 708 patients who presented with the
      diagnosis of fractured mandible between January 2009 and July 2013 at the Queen
      Elizabeth Hospital, Birmingham. We assessed the different factors that may have
      altered their outcomes, and found that delay before definitive fixation caused no
      harm in either the short or the long term.

PMID- 29174104
TI  - Reconstruction of intraoral defects after resection of cancer with two types of
      submental artery perforator flaps.
AB  - The submental island flap is a common choice for reconstruction of intraoral
      defects. To obtain a thinner, more pliable flap and get a better oncological
      result, the submental artery perforator flap has been proposed, and to assess its
      feasibility for closure of defects after resection of cancers of the oral cavity
      we studied 20 patients, each of whom was treated in this way. All the flaps were
      classified into those with septocutaneous perforators (n=16) and those with
      musculocutaneous perforators (n=4), and the main veins that drained the flaps
      were two submental veins (n=17). There were two patterns of venous drainage: in
      pattern 1 (n=9) the external jugular vein provided the primary venous drainage,
      and in pattern 2, the submental veins drained mainly into the facial vein, the
      common facial vein, and the internal jugular (n=10). In one patient the submental
      veins bypassed the facial vein to drain into the internal jugular. Eighteen of
      the 20 patients had no postoperative complications. The remaining two developed
      mild venous congestion of the flaps, which was resolved with conservative
      management and no skin loss. No local or regional recurrence was detected after a
      mean (range) follow-up of 21 (4-35) months. This is a simple, reliable flap that
      can be used for the reconstruction of intraoral defects after resections for
      cancer, but its oncological outcome still requires proof in long-term, large
      scale, clinical trials.

PMID- 29174105
TI  - Clinical outcomes of dental implants after use of tenting for bony augmentation:
      a systematic review.
AB  - The reconstruction of severely atrophic ridges is often challenging and
      complicated. We searched the Medline, Embase, and Cochrane databases for articles
      up to October 2015 that reported the success of all types of tenting for bony
      regeneration. We extracted data on the size and site of the defect, the number of
      patients, vertical and horizontal augmentation, survival of dental implants, and
      complications. Thirteen studies were included, which yielded data on 423 patients
      with 1111 dental implants. Follow-up periods were more than five years, severely
      resorbed mandibles were augmented vertically by up to 10mm, and the survival rate
      of the implants was over 97%. The mean (SD) gain in horizontal width by screw
      tenting was 3 (0.63)mm, and over 97.6% of dental implants in cortical tenting
      investigations survived. A tenting approach may reduce the need for large
      autogenous bone grafts in the reconstruction of severely atrophic ridges and
      local bony defects, and improves the survival of implants.

PMID- 29174106
TI  - A rapid qualitative assessment of oral cholera vaccine anticipated acceptability
      in a context of resistance towards cholera intervention in Nampula, Mozambique.
AB  - INTRODUCTION: While planning an immunization campaign in settings where public
      health interventions are subject to politically motivated resistance, designing
      context-based social mobilization strategies is critical to ensure community
      acceptability. In preparation for an Oral Cholera Vaccine campaign implemented in
      Nampula, Mozambique, in November 2016, we assessed potential barriers and levers
      for vaccine acceptability. METHODS: Questionnaires, in-depth interviews, and
      focus group discussions, as well as observations, were conducted before the
      campaign. The participants included central and district level government
      informants (national immunization program, logistics officers, public health
      directors, and others), community leaders and representatives, and community
      members. RESULTS: During previous well chlorination interventions, some
      government representatives and health agents were attacked, because they were
      believed to be responsible for spreading cholera instead of purifying the wells.
      Politically motivated resistance to cholera interventions resurfaced when an OCV
      campaign was considered. Respondents also reported vaccine hesitancy related to
      experiences of problems during school-based vaccine introduction, rumors related
      to vaccine safety, and negative experiences following routine childhood
      immunization. Despite major suspicions associated with the OCV campaign,
      respondents' perceived vulnerability to cholera and its perceived severity seem
      to override potential anticipated OCV vaccine hesitancy. DISCUSSION: Potential
      hesitancy towards the OCV campaign is grounded in global insecurity, social
      disequilibrium, and perceived institutional negligence, which reinforces a
      representation of estrangement from the central government, triggering suspicions
      on its intentions in implementing the OCV campaign. Recommendations include a
      strong involvement of community leaders, which is important for successful social
      mobilization; representatives of different political parties should be equally
      involved in social mobilization efforts, before and during campaigns; and public
      health officials should promote other planned interventions to mitigate the lack
      of trust associated with perceived institutional negligence. Successful past
      initiatives include public intake of purified water or newly introduced
      medication by social mobilizers, teachers or credible leaders.

PMID- 29174107
TI  - Assessing the safety of hepatitis B vaccination during pregnancy in the Vaccine
      Adverse Event Reporting System (VAERS), 1990-2016.
AB  - BACKGROUND: The safety of hepatitis B vaccination during pregnancy has not been
      well studied. OBJECTIVE: We characterized adverse events (AEs) after hepatitis B
      vaccination of pregnant women reported to the Vaccine Adverse Event Reporting
      System (VAERS), a spontaneous reporting surveillance system. METHODS: We searched
      VAERS for AEs reports involving pregnant women who received hepatitis B vaccine
      from January 1, 1990-June 30, 2016. All reports and available medical records
      were reviewed by physicians. Observed AEs were compared to expected AEs and known
      rates of pregnancy outcomes to assess for any unexpected safety concern. RESULTS:
      We found 192 reports involving pregnant women following hepatitis B vaccination
      of which 110 (57.3%) described AEs; 12 (6.3%) were classified as serious; one
      newborn death was identified in a severely premature delivery, and there were no
      maternal deaths. Eighty-two (42.7%) reports did not describe any AEs. Among
      pregnancies for which gestational age was reported, most women were vaccinated
      during the first trimester, 86/115 (74.7%). Among reports describing an AE, the
      most common pregnancy-specific outcomes included spontaneous abortion in 23
      reports, preterm delivery in 7 reports, and elective termination in 5 reports.
      The most common non-pregnancy specific outcomes were general disorders and
      administration site conditions, such as injection site and systemic reactions, in
      21 reports. Among 22 reports describing an AE among infants born to women
      vaccinated during pregnancy, 5 described major birth defects each affecting
      different organ systems. CONCLUSION: Our analysis of VAERS reports involving
      hepatitis B vaccination during pregnancy did not identify any new or unexpected
      safety concerns.

PMID- 29174108
TI  - Association of prior HPV vaccination with reduced preterm birth: A population
      based study.
AB  - BACKGROUND: Emerging evidence suggests that HPV infection is associated with
      negative pregnancy outcomes such as preterm birth (PTB), and pre-eclampsia. We
      aimed to determine if prior HPV vaccination reduced adverse pregnancy outcomes.
      METHODS: A New Zealand population-based retrospective study linking first
      pregnancy outcome data (2008-2014 n = 35,646) with prior quadrivalent HPV
      vaccination status. Primary outcomes were likelihood (odds ratios, ORs) of PTB,
      pre-eclampsia, and stillbirth. Exposure groups were based on HPV vaccination.
      Adjusted ORs were calculated for each outcome, controlling for mother's age at
      delivery, ethnicity, socioeconomic status, health board region at time of
      delivery, and body mass index and smoking status at time of registration with
      maternity care provider. RESULTS: Mother's mean age at delivery was 19 (SD 2.1)
      years. Of 34,994 the pregnancies included in the final study analyses 62.3% of
      women were unvaccinated, 11.0% vaccinated with one or two doses and 27.7%
      vaccinated with three doses prior to pregnancy. PTB (OR: 0.87; CI 0.78, 0.96))
      was significantly lower for women who previously received the HPV vaccine. A dose
      response effect was found with each successive dose received decreasing the
      likelihood of PTB. No associations between the vaccinated and unvaccinated groups
      were shown for pre-eclampsia or stillbirth. CONCLUSIONS: Prior receipt of the
      quadrivalent HPV vaccine was associated with a significant reduction in PTB
      (13%); suggesting that HPV vaccination may be effective in reducing PTB. The
      potential global public health impact is considerable and there is urgency to
      undertake further research to replicate and explore these findings.

PMID- 29174109
TI  - Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04
      adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose
      schedules in girls aged 9-14 years: Results to month 36 from a randomized trial.
AB  - : This observer-blind study (clinicaltrials.gov NCT01462357) compared the
      immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted
      vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or
      3D of 4vHPV] in 1075 healthy girls aged 9-14 years. Girls were randomized (1:1:1)
      to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0,
      6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls,
      respectively, returned for the concluding visit at M36. Superiority was
      demonstrated at M7 and M12; comparison of the immune response to both vaccine
      antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at
      subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I;
      N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18
      specific T-cell- and B-cell-mediated immune responses and safety were also
      investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18
      group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC,
      geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for
      2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18)
      higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based
      neutralisation assay. Numbers of circulating CD4+ T cells and B cells appeared
      similar across groups. Safety was in line with the known safety profiles of both
      vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by
      2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls
      aged 9-14 years. CLINICAL TRIAL REGISTRATION: NCT0146235.

PMID- 29174110
TI  - [Do analgesic sweet solutions in neonates influence glycemia? A literature
      review].
AB  - Sweet solutions are one of the most widely used nonpharmacologic analgesics used
      for newborns. They alleviate mild to moderate pain induced by painful procedures.
      They are used daily in neonatal intensive care units before a venepuncture or a
      heel stick, especially for a blood-sugar measurement. It is agreed that analgesic
      sweet solutions do not modify glycemia results. This nevertheless remains a
      recurrent question that the present review attempts to answer.

PMID- 29174111
TI  - [Pseudomonas aeruginosa in post-piercing perichondritis: Two case reports].
AB  - The frequency of body piercing has increased in France over the past few years,
      particularly among teenagers. Piercing can be performed at different sites on the
      body, especially in the cartilage of the ears. We relate two cases of Pseudomonas
      aeruginosa chondritis. A 10-year retrospective study at the Marseille University
      Hospital found no additional pediatric cases. These infectious complications can
      sometimes be necrotizing. It is therefore important to inform the medical staff
      on the hygiene measures that need to be respected and the patients on the
      treatment to follow after the piercing as well as the signs to watch for,
      possibly indicating chondritis. The esthetic consequences depend on early
      diagnosis.

PMID- 29174112
TI  - Mechanism of Rhinella icterica (Spix, 1824) toad poisoning using in vitro
      neurobiological preparations.
AB  - The biological activity of Rhinella icterica toxic secretion (RITS) was evaluated
      on chick neuromuscular junctions, rat hearts tissue and mice hippocampal slices.
      At chick biventer cervicis preparation, RITS (5, 10 and 20MUg/mL) produced a
      concentration-independent irreversible neuromuscular blockade, which was preceded
      by a transitory increase of muscle twitch tension with the lowest concentration,
      in 120min recordings. In this set of experiments, RITS incubation partially
      prevented the curare neuromuscular blockade. The assessment of chick biventer
      cervicis muscle acetylcholinesterase (AChE) in the presence of RITS showed a
      significant inhibition of the enzyme, similarly to neostigmine. The incubation of
      muscles with digoxin or ouabain mimicked the poison activity by increasing the
      amplitude of the twitches followed by a progressive depression of the muscle
      strength. In addition, RITS demonstrated a digitalic-like activity, by inhibiting
      significantly the cardiac Na+, K+-ATPase. When the central nervous system was
      accessed, RITS induced an increase in the cell viability, in the lowest
      concentration. In addition, the poison protected slices subject to oxygen/glucose
      deprivation. Altogether, these data indicate that the poisonous extract of R.
      icterica is able to interfere with peripheral and central neurotransmission,
      probably due to a direct interaction with AChE, calcium channels and Na+, K+
      ATPase. A further investigation upon the poison toxic components will unveil the
      components involved in such a pharmacological activity and the potential
      biotechnological application of this poison.

PMID- 29174113
TI  - Ghrelin protects retinal ganglion cells against rotenone via inhibiting
      apoptosis, restoring mitochondrial function, and activating AKT-mTOR signaling.
AB  - Ghrelin, a 28-amino acid peptide hormone, has protective effects on neuronal
      cells. The present study aimed to examine the neuroprotective effects of ghrelin
      on the rat retinal ganglion cells in the rotenone-induced in vitro model of
      Parkinson's disease (PD). Cell viability and cell apoptosis were determined by
      MTT assay and flow cytometry, respectively. Mitochondrial functions were detected
      by mitochondrial complex I activity assay and mitochondrial membrane potential
      (MMP) assay. The mRNA and protein expression levels were determined by qRT-PCR
      and western blot, respectively. Rotenone significantly suppressed cell viability
      and increased cell apoptosis, also decreased the mitochondrial complex I activity
      as well as MMP in rat retinal ganglion cell line (RGC-5). Growth hormone
      secretagogue receptor (Ghsr) siRNA transfection significantly suppressed the
      expression of Ghsr in RGC-5 cells. Ghrelin treatment attenuated the effects of
      rotenone-induced changes in cell viability, cell apoptosis and mitochondrial
      functions in RGC-5 cells. Post-transcriptional suppression by Ghsr siRNA
      transfection and treatment with GHS-R antagonist, YIL781, both significantly
      attenuated the effects of ghrelin in RGC-5 cells. Rotenone decreased the protein
      levels of Bcl-2 and increased the protein levels of Bax, cleaved caspase-3 and
      cleaved caspase-9, and this effect was reversed by ghrelin treatment. Ghrelin
      also prevented the inhibitory effects of rotenone on the AKT-mTOR signaling. The
      effects of ghrelin on the rotenone-induced changes in apoptosis-related protein
      levels and AKT-mTOR signaling were attenuated by Ghsr siRNA transfection and
      treatment with YIL781 in the RGC-5 cells. In addition, both rapamycin and AKT
      inhibitor IV pre-treatment significantly attenuated the effects of ghrelin on
      rotenone-induced changes in cell viability and cell apoptosis. In conclusion,
      ghrelin by acting on the GSH-R to protect rat retinal ganglion cells against
      rotenone via inhibiting apoptosis and restore mitochondrial functions in RGC-5
      cells, and this effect was partially associated with the AKT-mTOR signaling
      pathway in RGC-5 cells.

PMID- 29174114
TI  - The mechanism of skin lipids influencing skin status.
AB  - Skin lipids, compose of sebocyte-, keratinocyte-, and microbe- derived lipids,
      dramatically influence skin status by different mechanisms. (I) Physical
      chemistry function: They are "mortar" to establish the physico-chemical barrier
      function of skin; (II) Biochemistry function: They function as signals in the
      complex signaling network originating at the epidermal level; (III) Microecology
      function: Sebocyte- and keratinocyte-derived lipids vary the composition of
      microbial skin flora, and microorganisms metabolize them to produce lipids as
      signal starting signaling transduction. Importantly, further research needs
      lipidiomics, more powerful analytical ability and high-throughput manner, to
      identify skin lipid components into individual species. The validation of lipid
      structure and function to research the process that lipid species involved in.
      Additional, the integration of lipidomics data with other omics strategies can
      develop the power to study the mechanism of skin lipids influencing skin status.

PMID- 29174115
TI  - Modeling clinical efficacy of the S1P receptor modulator ponesimod in psoriasis.
AB  - BACKGROUND: Ponesimod is currently the only S1P receptor modulator studied in
      psoriasis. In a dose-finding study, the active doses showed similar efficacy.
      OBJECTIVE: Prediction of efficacy at lower doses to aid clinical phase 3 planning
      with respect to dose selection, duration of treatment, and patient inclusion
      criteria based on pharma-co-kinetic/pharmacodynamic (PK/PD) modeling and
      simulation. METHODS: The dose-finding study treated 326 patients (67 on placebo,
      126 on 20mg, and 133 on 40mg) over 16 weeks. PK/PD modeling of steady-state
      trough concentrations and longitudinal PASI scores was employed to characterize
      data and simulate scenarios. RESULTS: PASI score continually decreased with time
      on ponesimod treatment, reaching a plateau at 16 weeks. Absolute and relative
      (percent) PASI score change was larger in patients with higher PASI score at
      baseline. Doses below 10mg were predicted to show lower efficacy than doses of
      10mg and higher. CONCLUSION: Concentration-response modeling was able to predict
      the efficacy of doses that were not studied. In psoriasis patients, a dose of
      10mg (not administered in the study) was predicted to show efficacy similar to
      20mg. Disease status (PASI score at baseline) as study inclusion criterion has
      pronounced influence on study outcome.

PMID- 29174116
TI  - Hardening of particle/oil/water suspensions due to capillary bridges:
      Experimental yield stress and theoretical interpretation.
AB  - Suspensions of colloid particles possess the remarkable property to solidify upon
      the addition of minimal amount of a second liquid that preferentially wets the
      particles. The hardening is due to the formation of capillary bridges (pendular
      rings), which connect the particles. Here, we review works on the mechanical
      properties of such suspensions and related works on the capillary-bridge force,
      and present new rheological data for the weakly studied concentration range 30-55
      vol% particles. The mechanical strength of the solidified capillary suspensions,
      characterized by the yield stress Y, is measured at the elastic limit for various
      volume fractions of the particles and the preferentially wetting liquid. A
      quantitative theoretical model is developed, which relates Y with the maximum of
      the capillary-bridge force, projected on the shear plane. A semi-empirical
      expression for the mean number of capillary bridges per particle is proposed. The
      model agrees very well with the experimental data and gives a quantitative
      description of the yield stress, which increases with the rise of interfacial
      tension and with the volume fractions of particles and capillary bridges, but
      decreases with the rise of particle radius and contact angle. The quantitative
      description of capillary force is based on the exact theory and numerical
      calculation of the capillary bridge profile at various bridge volumes and contact
      angles. An analytical formula for Y is also derived. The comparison of the
      theoretical and experimental strain at the elastic limit reveals that the
      fluidization of the capillary suspension takes place only in a deformation zone
      of thickness up to several hundred particle diameters, which is adjacent to the
      rheometer's mobile plate. The reported experimental results refer to water
      continuous suspension with hydrophobic particles and oily capillary bridges. The
      comparison of data for bridges from soybean oil and hexadecane surprisingly
      indicate that the yield strength is greater for the suspension with soybean oil
      despite its lower interfacial tension against water. The result can be explained
      with the different contact angles of the two oils in agreement with the
      theoretical predictions. The results could contribute for a better understanding,
      quantitative prediction and control of the mechanical properties of three-phase
      capillary suspensions solid/liquid/liquid.

PMID- 29174117
TI  - RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect
      metabolic changes and insulin resistance after a standard hypocaloric diet.
AB  - BACKGROUND: Role of BDNF variants on change in body weight and cardiovascular
      risk factors after weight loss remains unclear in obese patients. OBJECTIVE: Our
      aim was to analyze the effects of rs10767664 BDNF gene polymorphism on body
      weight, cardiovascular risk factors and serum adipokine levels after a standard
      hypocaloric diet in obese subjects. DESIGN: A Caucasian population of 80 obese
      patients was analyzed before and after 3months on a standard hypocaloric diet.
      RESULTS: Fifty patients (62.5%) had the genotype AA and 30 (37.5%) subjects had
      the next genotypes; AT (25 patients, 31.3%) or TT (5 study subjects, 6.3%)
      (second group). In non T allele carriers, the decreases in weight-3.4+/-2.9kg (T
      allele group -1.7+/-2.0kg:p=0.01), BMI -1.5+/-0.2kg (T allele group -1.2+/
      0.5kg:p=0.02), fat mass-2.3+/-1.1kg (T allele group -1.7+/-0.9kg:p=0.009), waist
      circumference-3.8+/-2.4cm (T allele group -2.1+/-3.1cm:p=0.008), triglycerides 
      13.2+/-7.5mg/dl (T allele group +2.8+/-1.2mg/dl:p=0.02), insulin -2.1+/-1.9mUI/L
      (T allele group -0.3+/-1.0mUI/L:p=0.01), HOMA-IR -0.9+/-0.4 (T allele group 
      0.1+/-0.8:p=0.01) and leptin -10.1+/-9.5ng/dl (T allele group -3.1+/
      0.2ng/dl:p=0.01) were higher than T allele carriers. CONCLUSION: rs10767664
      variant of BDNF gene modify anthropometric and biochemical changes after weight
      loss with a hypocaloric diet.

PMID- 29174118
TI  - Poor performance of clinical prediction models: the harm of commonly applied
      methods.
AB  - OBJECTIVE: To evaluate limitations of common statistical modeling approaches in
      deriving clinical prediction models and explore alternative strategies. STUDY
      DESIGN AND SETTING: A previously published model predicted the likelihood of
      having a mutation in germline DNA mismatch repair genes at the time of diagnosis
      of colorectal cancer. This model was based on a cohort where 38 mutations were
      found among 870 participants, with validation in an independent cohort with 35
      mutations. The modeling strategy included stepwise selection of predictors from a
      pool of over 37 candidate predictors and dichotomization of continuous
      predictors. We simulated this strategy in small subsets of a large contemporary
      cohort (2,051 mutations among 19,866 participants) and made comparisons to other
      modeling approaches. All models were evaluated according to bias and
      discriminative ability (concordance index, c) in independent data. RESULTS: We
      found over 50% bias for five of six originally selected predictors, unstable
      model specification, and poor performance at validation (median c = 0.74). A
      small validation sample hampered stable assessment of performance. Model
      prespecification based on external knowledge and using continuous predictors led
      to better performance (c = 0.836 and c = 0.852 with 38 and 2,051 events
      respectively). CONCLUSION: Prediction models perform poorly if based on small
      numbers of events and developed with common but suboptimal statistical
      approaches. Alternative modeling strategies to best exploit available predictive
      information need wider implementation, with collaborative research to increase
      sample sizes.

PMID- 29174119
TI  - Engaging the Front Line: Tapping into Hospital-Wide Quality and Safety
      Initiatives.
AB  - Healthcare increasingly is moving from volume- to value-based care, with an
      emphasis on linking a larger percentage of payments to the quality of care
      provided. There is a renewed interest in designing a focused, strategic approach
      to quality and safety education and engagement of trainees in hospital-wide
      quality, safety, and patient experience initiatives. Hospitals, trainees, and
      patients benefit as a result of engaging frontline learners in these activities.
      Hospitals can leverage the intelligence from the front line to contribute to
      improved hospital safety, increased employee and patient engagement, and better
      identification of vulnerable areas of safety risks. Trainees benefit from
      increased engagement by acquiring fundamentals in quality and safety; are able to
      satisfy Clinical Learning Environment Review recommendations; have an opportunity
      to practice a number of skill sets (leadership, communication, collaboration);
      and complete quality and safety hands-on projects. Patients benefit from a more
      engaged work force, safer environment for their healthcare, and an improved
      overall experience. In this article, the current state of the Johns Hopkins
      Department of Anesthesiology and Critical Care Medicine's efforts to engage its
      front line in quality, safety, and patient experience initiatives that are in
      evolutionary phases of implementation is presented. Evolutionary concepts relate
      to the Johns Hopkins Health System and the aim of its training program to
      continuously improve and innovate.

PMID- 29174120
TI  - Regional Cerebral Oxygen Saturation Level in Left Ventricular Assist Device
      Surgery: Is This the Crystal Ball?

PMID- 29174121
TI  - Pro: Third-Generation Hydroxyethyl Starch Solution Is Safe and Effective for
      Plasma Volume Expansion During Cardiac Surgery.

PMID- 29174122
TI  - Myopathy and Noncompaction Detected After Malignant Hyperthermia During Cardiac
      Surgery.

PMID- 29174123
TI  - Intraoperative Anesthetic Management of Lung Transplantation: Center-Specific
      Practices and Geographic and Centers Size Differences.
AB  - OBJECTIVE: Although increasing evidence in lung transplantation (LTx) suggests
      that intraoperative management could influence outcomes, there are no guidelines
      available regarding intraoperative management of LTx. The overall goal of the
      study was to assess geographic and center volume-specific clinical practices in
      perioperative management. DESIGN: Prospective data analysis. SETTING: Online
      survey from a single-center university hospital. PARTICIPANTS: European and non
      European LTx centers. INTERVENTIONS: An online survey was sent to 176 centers
      currently performing LTx procedures. It covered organizational data, general
      anesthesia considerations, fluid therapy and coagulation, antioxidant and anti
      inflammatory therapies, and ventilation strategies. MEASUREMENTS AND MAIN
      RESULTS: The response rates were 57.5% (n = 42) from European and 32% (n = 33)
      from non-European countries. Significant differences between European and non
      European countries were use of volatile hypnotics (p = 0.016), use of sufentanil
      (p < 0.001), inotropic agents (p = 0.001) and colloid infusion (p < 0.001), use
      of calibrated pulse contour analysis (p = 0.004), use of intraoperative
      traditional laboratory-based coagulation tests (p = 0.001) and platelet function
      analysis (p = 0.005), and use of higher peak inspiratory pressure (p = 0.009).
      Center volume-specific differences were use of fentanyl (p = 0.03) and the use of
      higher peak inspiratory pressure (p = 0.005) for ventilation. Induction of
      anesthesia and use of advanced hemodynamic monitoring, therapy for pulmonary
      hypertension, antioxidant and anti-inflammatory therapies, and ventilation
      strategies were not different among the centers. CONCLUSIONS: This survey
      demonstrated for the first time statistically significant differences among
      European and non-European centers and among low- versus high-volume centers
      regarding intraoperative management during LTx. These observations will be of
      some guidance for the LTx community and may trigger more extensive studies.

PMID- 29174124
TI  - Fallacies of CT Scan in Assessment of Mediastinal Mass Causing Difficult Airway.

PMID- 29174125
TI  - Refractory Heart Failure After Failed Subcutaneous Implantable Cardioverter
      Defibrillator Defibrillation Testing: The Potential Value of Early Mechanical
      Circulatory Support.

PMID- 29174126
TI  - In Response To: Myopathy and Noncompaction Detected After Malignant Hyperthermia
      During Cardiac Surgery.

PMID- 29174127
TI  - Heart failure in an ageing population.

PMID- 29174129
TI  - Department of Error.

PMID- 29174130
TI  - Stimulated intrauterine insemination for unexplained subfertility.

PMID- 29174128
TI  - Intrauterine insemination with ovarian stimulation versus expectant management
      for unexplained infertility (TUI): a pragmatic, open-label, randomised,
      controlled, two-centre trial.
AB  - BACKGROUND: Women with unexplained infertility are often offered intrauterine
      insemination (IUI) with ovarian stimulation as an alternative to in-vitro
      fertilisation (IVF). However, little evidence exists that IUI is an effective
      treatment. In 2013, the UK National Institute for Health and Care Excellence
      recommended that IUI should not be routinely offered for couples with unexplained
      infertility. METHODS: For this pragmatic, open-label, randomised, controlled, two
      centre study, we enrolled women attending two fertility clinics in New Zealand
      with unexplained infertility and an unfavourable prognosis of natural conception.
      Participants were randomly assigned (1:1) using a computer-generated
      randomisation sequence, prepared by an independent statistician, to either three
      cycles of IUI with ovarian stimulation (with either oral clomifene citrate [50
      150 mg, days 2-6] or oral letrozole [2.5-7.5 mg, days 2-6], with choice of
      ovarian stimulation made by the clinic) or three cycles of expectant management
      (couples advised to be sexually active around the likely time of ovulation and
      provided with a diary to record the first day of each menstrual cycle and dates
      of sexual activity) in blocks of four, six, and ten, without stratification. The
      participating couple and the clinicians were informed of treatment allocation.
      The primary outcome was cumulative livebirth rate in the intention-to-treat
      population. The safety analyses were done in the intention-to-treat population.
      This study was prospectively registered with the Australian and New Zealand
      Clinical Trials Register, number ACTRN12612001025820. FINDINGS: Between March 12,
      2013, and May 12, 2016, we randomly assigned 101 women to IUI with ovarian
      stimulation and 100 to expectant management, all of whom were included in the
      primary efficacy analysis and safety analyses. Women assigned to IUI had a higher
      cumulative livebirth rate than women assigned to expectant management (31 [31%]
      livebirths among 101 women vs nine [9%] livebirths among 100 women; risk ratio
      [RR] 3.41, 95% CI 1.71-6.79; p=0.0003). Of 31 livebirths in the IUI group, 23
      resulted from IUI cycles and eight were conceived without assistance before or
      between IUI cycles. Of nine livebirths in the expectant management group, one
      patient was pregnant from IUI with ovarian stimulation at study entry and one had
      received off-protocol treatment (IVF). Two sets of twins were born, both in the
      IUI group (one from a cancelled cycle for over-response). INTERPRETATION: IUI
      with ovarian stimulation is a safe and effective treatment for women with
      unexplained infertility and an unfavourable prognosis for natural conception.
      FUNDING: Auckland Medical Research Foundation, Evelyn Bond Fund of Auckland
      District Health Board, Mercia Barnes Trust of Royal Australian and New Zealand
      College of Obstetricians and Gynaecologists, Maurice and Phyllis Paykel Trust,
      and The Nurture Foundation for Reproductive Research.

PMID- 29174131
TI  - Phase 1b/2a Trial of the Superoxide Dismutase Mimetic GC4419 to Reduce
      Chemoradiotherapy-Induced Oral Mucositis in Patients With Oral Cavity or
      Oropharyngeal Carcinoma.
AB  - PURPOSE: To assess the safety of the superoxide dismutase mimetic GC4419 in
      combination with radiation and concurrent cisplatin for patients with oral cavity
      or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce
      severe oral mucositis (OM). PATIENTS AND METHODS: Patients with locally advanced
      OCC treated with definitive or postoperative intensity modulated radiation
      therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion,
      ending <60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose
      and duration escalation study. Oral mucositis was assessed twice weekly during
      and weekly after IMRT. RESULTS: A total of 46 patients received GC4419 in 11
      separate dosing and duration cohorts: dose escalation occurred in 5 cohorts
      receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in 3 cohorts
      receiving 112 mg/d over 4 to 6 weeks (n=12), and then 3 additional cohorts
      receiving 30 or 90 mg/d over 6 to 7 weeks (n=14). A maximum tolerated dose was
      not reached. One dose-limiting toxicity (grade 3 gastroenteritis and vomiting
      with hyponatremia) occurred in each of 2 separate cohorts at 112 mg.
      Nausea/vomiting and facial paresthesia during infusion seemed to be GC4419 dose
      related. Severe OM occurred through 60 Gy in 4 of 14 patients (29%) dosed for 6
      to 7 weeks, with median duration of only 2.5 days. CONCLUSIONS: The safety of
      GC4419 concurrently with chemoradiation for OCC was acceptable. Toxicities
      included nausea/vomiting and paresthesia. Doses of 30 and 90 mg/d administered
      for 7 weeks were selected for further study. In an exploratory analysis, severe
      OM seemed less frequent and briefer than expected.

PMID- 29174132
TI  - Development of magnetic dispersive solid phase extraction using toner powder as
      an efficient and economic sorbent in combination with dispersive liquid-liquid
      microextraction for extraction of some widely used pesticides in fruit juices.
AB  - In this study, for the first time, a magnetic dispersive solid phase extraction
      method using an easy-accessible, cheap, and efficient magnetic sorbent (toner
      powder) combined with dispersive liquid-liquid microextraction has been developed
      for the extraction and preconcentration of some widely used pesticides (diazinon,
      ametryn, chlorpyrifos, penconazole, oxadiazon, diniconazole, and fenazaquin) from
      fruit juices prior to their determination by gas chromatography-flame ionization
      detection. In this method, the magnetic sorbent is mixed with an appropriate
      dispersive solvent (methanol-water, 80:20, v/v) and then injected into an aqueous
      sample containing the analytes. By this action the analytes are rapidly adsorbed
      on the sorbent by binding to its carbon. The sorbent particles are isolated from
      the aqueous solution in the presence of an external magnetic field. Then an
      appropriate organic solvent (acetone) is used to desorb the analytes from the
      sorbent. Finally, the obtained supernatant is mixed with an extraction solvent
      and injected into deionized water in order to achieve high enrichment factors and
      sensitivity. Several significant factors affecting the performance of the
      introduced method were investigated and optimized. Under the optimum experimental
      conditions, the extraction recoveries of the proposed method for the selected
      analytes ranged from 49-75%. The relative standard deviations were <=7% for intra
      (n = 6) and inter-day (n = 4) precisions at a concentration of 10 MUg L-1 of
      each analyte. The limits of detection were in the range of 0.15-0.36 MUg L-1.
      Finally, the applicability of the proposed method was evaluated by analysis of
      the selected analytes in some fruit juices.

PMID- 29174133
TI  - Optimization for quick, easy, cheap, effective, rugged and safe extraction of
      mycotoxins and veterinary drugs by response surface methodology for application
      to egg and milk.
AB  - A multiclass method was proposed for the simultaneous determination of various
      classes of veterinary drugs (n = 65), mycotoxins and metabolites (n = 39) in egg
      and milk by ultra-high performance liquid chromatography-tandem mass
      spectrometry. The contaminants were extracted by QuEChERS-based strategy
      including salt-out partitioning and dispersive solid-phase extraction for cleanup
      further. With the aim of maximizing throughput and extraction efficiency,
      Plackett-Burman design was employed initially for screening significant
      variables. And response surface methodology based on central composite design was
      conducted to achieve optimal conditions in details: 3.35% (v/v) of formic acid in
      acetonitrile, 1.2 g of NaCl, 0.5 g of anhydrous NaAc, 300 mg of C18 and 140 mg of
      primary secondary amine. Satisfactory analytical characteristics in validation,
      in aspects of accuracy (70%-105% for mycotoxins and quinolones, 55%-80% for
      sulphonamides and 40%-105% for other veterinary drugs), precision (inter-day RSDs
      < 14%) and sensitivity (LOQs ranged from 0.01 MUg/kg to 31 MUg/kg), were achieved
      under the optimized conditions. The matrix effects were evaluated and compensated
      by the use of matrix-matched calibration curves (R2 > 0.987). In practice, 45
      eggs and 30 milk samples were investigated by the established method, of which
      positive finding aflatoxin in milk and sterigmatocystin in eggs.

PMID- 29174134
TI  - Design of two-column batch-to-batch recirculation to enhance performance in ion
      exchange chromatography.
AB  - Preparative liquid chromatography is a separation technique widely used in the
      manufacturing of fine chemicals and pharmaceuticals. A major drawback of
      traditional single-column batch chromatography step is the trade-off between
      product purity and process performance. Recirculation of impure product can be
      utilized to make the trade-off more favorable. The aim of the present study was
      to investigate the usage of a two-column batch-to-batch recirculation process
      step to increase the performance compared to single-column batch chromatography
      at a high purity requirement. The separation of a ternary protein mixture on ion
      exchange chromatography columns was used to evaluate the proposed process. The
      investigation used modelling and simulation of the process step, experimental
      validation and optimization of the simulated process. In the presented case the
      yield increases from 45.4% to 93.6% and the productivity increases 3.4 times
      compared to the performance of a batch run for a nominal case. A rapid
      concentration build-up product can be seen during the first cycles, before the
      process reaches a cyclic steady-state with reoccurring concentration profiles.
      The optimization of the simulation model predicts that the recirculated salt can
      be used as a flying start of the elution, which would enhance the process
      performance. The proposed process is more complex than a batch process, but may
      improve the separation performance, especially while operating at cyclic steady
      state. The recirculation of impure fractions reduces the product losses and
      ensures separation of product to a high degree of purity.

PMID- 29174135
TI  - Analyses of simulated moving bed with internal temperature gradients for binary
      separation of ketoprofen enantiomers using multi-objective optimization: Linear
      equilibria.
AB  - Gradient operation of a simulated moving bed (SMB) can improve the separation and
      purification performance by adjusting adsorption strength in each individual zone
      according to its functional role. The feasibility of an internal temperature
      gradient (ITG) established by a difference between feed and desorbent
      temperatures for binary separation of ketoprofen enantiomers was investigated
      based on simultaneous optimization of purity and productivity of S-ketoprofen,
      the preferentially adsorbed species and desired product. ITG operation with a
      temperature difference of 20K has a unit productivity higher than isothermal mode
      by about 20%. Due to the combined effects of temperature transition and
      downstream dilution, concentration profile may exhibit a remarkable peak and a
      pattern of two-step drop in the temperature descending and ascending areas,
      respectively. Both areas, if properly located under optimal conditions, are
      favorable for unit productivity, which cannot be predicted by the direct use of
      triangle theory and average Henry's constants. Modifications of the SMB
      operations to reduce solvent consumption were also discussed based on analyses of
      parametric sensitivity and internal concentration profiles.

PMID- 29174136
TI  - Mixed functional monomers-based monolithic adsorbent for the effective extraction
      of sulfonylurea herbicides in water and soil samples.
AB  - Effective extraction is a key step in the determination of sulfonylurea
      herbicides (SUHs) in complicated samples. According to the chemical properties of
      SUHs, a new monolithic adsorbent utilizing acrylamidophenylboronic acid and
      vinylimidazole as mixed functional monomers was synthesized. The new adsorbent
      was employed as the extraction phase of multiple monolithic fiber solid-phase
      microextraction (MMF-SPME) of SUHs, and the extracted SUHs were determined by
      high-performance liquid chromatography with diode array detection (HPLC-DAD).
      Results well evidence that the prepared adsorbent could extract SUHs in
      environmental waters and soil effectively through multiply interactions such as
      boronate affinity, dipole-dipole and pi-pi interactions. Under the optimized
      extraction conditions, the limits of detection for target SUHs in environmental
      water and soil samples were 0.018-0.17MUg/L and 0.14-1.23MUg/kg, respectively. At
      the same time, the developed method also displayed some analytical merits
      including wide linear dynamic ranges, good method reproducibility, satisfactory
      sensitivity and low consume of organic solvent. Finally, the developed were
      successfully applied to monitor trace SUHs in environmental water and soil
      samples. The recoveries at three fortified concentrations were in the range of
      70.6-119% with RSD below 11% in all cases. The obtained results well demonstrate
      the excellent practical applicability of the developed MMF-SPME-HPLC-DAD method
      for the monitoring of SUHs in water and soil samples.

PMID- 29174137
TI  - Multimodality Imaging Spectrum of the Extranodal Lymphomas in the Head and Neck-A
      Pictorial Review.
AB  - Lymphoma is the second most common malignant neoplasm of the head and neck
      region, involving the nodal and/or extranodal sites or both in a variable
      fashion. Lymphoma may mimic a variety of tumors in this region depending on the
      subsite involved. The usual presentation of lymphomatous disease is presence of
      multiple enlarged, often conglomerate, lymph nodes without significant necrosis.
      Extranodal lymphomas demonstrate more complex radiologic features, but careful
      evaluation can identify distinct imaging patterns to suggest extranodal
      lymphomatous disease from other more common lesions. Knowledge of these imaging
      features can help raise suspicion for lymphoma as a differential consideration.
      This can be of critical importance since further work-up and management can be
      vastly different between lymphomatous disease and other disease entities. The
      authors present a pictorial review of the spectrum of imaging findings in
      extranodal head and neck lymphomas.

PMID- 29174138
TI  - Development and Assessment of a Multidisciplinary Radiology ContrastReaction
      Training Course: Our Experience and Future Directions.

PMID- 29174139
TI  - Altered TGF-beta endocytic trafficking contributes to the increased signaling in
      Marfan syndrome.
AB  - The main cardiovascular alteration in Marfan syndrome (MFS) is the formation of
      aortic aneurysms in which augmented TGF-beta signaling is reported. However, the
      primary role of TGF-beta signaling as a molecular link between the genetic
      mutation of fibrillin-1 and disease onset is controversial. The
      compartmentalization of TGF-beta endocytic trafficking has been shown to
      determine a signaling response in which clathrin-dependent internalization leads
      to TGF-beta signal propagation, and caveolin-1 (CAV-1) associated internalization
      leads to signal abrogation. We here studied the contribution of endocytic
      trafficking compartmentalization to increased TGF-beta signaling in vascular
      smooth muscle cells (VSMC) from MFS patients. We examined molecular components
      involved in clathrin- (SARA, SMAD2) and caveolin-1- (SMAD7, SMURF2) dependent
      endocytosis. Marfan VSMC showed higher recruitment of SARA and SMAD2 to membranes
      and their increased interaction with TGF-beta receptor II, as well as higher
      colocalization of SARA with the early endosome marker EEA1. We assessed TGF-beta
      internalization using a biotinylated ligand (b-TGF-beta), which colocalized
      equally with either EEA1 or CAV-1 in VSMC from Marfan patients and controls.
      However, in Marfan cells, colocalization of b-TGF-beta with SARA and EEA1 was
      increased and accompanied by decreased colocalization with CAV-1 at EEA1-positive
      endosomes. Moreover, Marfan VSMC showed higher transcriptional levels and
      membrane enrichment of RAB5. Our results indicate that increased RAB5-associated
      SARA localization to early endosomes facilitates its TGF-beta receptor binding
      and phosphorylation of signaling mediator SMAD2 in Marfan VSMC. This is
      accompanied by a reduction of TGF-beta sorting into multifunctional vesicles
      containing cargo from both internalization pathways.

PMID- 29174140
TI  - Relation of Coronary Artery Calcium and Extra-Coronary Aortic Calcium to Incident
      Hypertension (from the Multi-Ethnic Study of Atherosclerosis).
AB  - Arterial calcification reflects an atherosclerotic process associated with
      vascular stiffness. Whether baseline coronary artery calcium (CAC) and extra
      coronary calcium (ECC), measured using noncontrast computed tomography imaging,
      are associated with incident hypertension is poorly understood. We studied
      participants from the Multi-Ethnic Study of Atherosclerosis without measured or
      self-reported hypertension at baseline. Incident hypertension was defined by
      blood pressure criteria (BP, >=140/90 mmHg), BP medication use, or both, and was
      assessed at in-person visits. We analyzed incident hypertension using
      multivariable-adjusted discrete-time proportional hazards models. Net
      reclassification improvement (NRI) assessed whether CAC reclassified hypertension
      risk when added to the Framingham hypertension risk score. Among 3,304 subjects
      analyzed, mean age was 59 +/- 10 years; 48% were male and 42% were white. There
      were 1,283 incident hypertension cases over a median (interquartile range) follow
      up time of 10.6 (4.5, 11.5) years. Each 1-unit increase in ln(CAC+1) was
      independently associated with a 12% higher risk of hypertension (95% confidence
      interval [CI] 9% to 16%). Relative to CAC = 0, patients with CAC >400 had a
      hazard ratio for incident hypertension of 2.2 (95% CI 1.8 to 2.9). There was no
      interaction by age, gender, or baseline BP (p = 0.43, 0.19, 0.09, respectively).
      Continuous NRI analyses demonstrated that CAC can reclassify risk of incident
      hypertension; NRI = 0.19 (95% CI 0.10 to 0.26). Furthermore, all measurements of
      ECC were significantly associated with incident hypertension, even after
      adjustment for CAC (hazard ratios ranging from 1.36 to 1.38). In conclusion,
      patients with CAC and ECC are at markedly higher risk of incident hypertension
      and may benefit from more intensified prevention efforts.

PMID- 29174141
TI  - Stability of virus-like particles of red-spotted grouper nervous necrosis virus
      in the aqueous state, and the vaccine potential of lyophilized particles.
AB  - Virus-like particles (VLPs) are multi protein complexes mimicking the structural
      properties of the native virus. The development of freeze-dried formulations of
      such complex protein structures remains a challenge. Red-spotted grouper nervous
      necrosis virus (RGNNV) causes mass mortality in fish culture, and RGNNV VLPs have
      been suggested to be promising vaccine candidates. In the present study, the
      stability of RGNNV VLPs in the liquid state was investigated over a 4-week
      period, along with the influence of freeze-drying on VLP stability. RGNNV VLPs
      were completely degraded after one week at 37  degrees C followed by 3 weeks at
      ambient temperature, and they were partially degraded after 4 weeks at 4  degrees
      C. Therefore, the inherent stability of RGNNV VLP in an aqueous milieu is
      insufficient for long-term storage. When RGNNV VLPs were freeze-dried in the
      presence or absence of sugar stabilizers, sorbitol was found to improve VLP
      stability whereas mannitol reduced it. VLP preparations freeze-dried with
      sorbitol or without stabilizer were as immunogenic as control (non-freeze dried)
      VLPs, whereas VLPs freeze-dried in mannitol were less immunogenic. These results
      indicate that freeze-dried RGNNV VLPs have potential as vaccines.

PMID- 29174142
TI  - Estimating probability of insemination success using milk progesterone
      measurements.
AB  - The aim of this study was to quantify the effects of progesterone profile
      features and other cow-level factors on insemination success to provide a real
      time predictor equation of probability of insemination success. Progesterone
      profiles from 26 dairy herds were analyzed and the effects of profile features
      (progesterone slope, cycle length, and cycle height) and cow traits (milk yield,
      parity, insemination during the previous estrus) on likelihood of artificial
      insemination success were estimated. The equation was fitted on a training data
      set containing data from 16 herds (6,246 estrous cycles from 3,404 lactations).
      The equation was tested on a testing data set containing data from 10 herds
      (8,105 estrous cycles from 3,038 lactations). Predictors were selected to be
      implemented in the final equation if adding them to a base model correcting for
      timing of insemination and parity decreased the overall likelihood distance of
      the model. Selected variables (cycle length, milk yield, cycle height, and
      insemination during the previous estrus) were used to build the final model using
      a stepwise approach. Predictors were added 1 by 1 in different order, and the
      model that had the smallest likelihood distance was selected. The final equation
      included the variables timing of insemination, parity, milk yield, cycle length,
      cycle height, and insemination during the previous estrus, respectively. The
      final model was applied to the testing data set and area under the curve (AUC)
      was calculated. On the testing data set, the final model had an AUC of 58%. When
      the farm effect was taken into account, the AUC increased to 63%. This equation
      can be implemented on farms that monitor progesterone and can support the farmer
      in deciding when to inseminate a cow. This can be the first step in moving the
      focus away from the current paradigm associated with poorer estrus detection,
      where each detected estrus is automatically inseminated, to near perfect estrus
      detection, where the question is which estrous cycle is worth inseminating?

PMID- 29174143
TI  - Intramammary infections with different non-aureus staphylococci in dairy cows.
AB  - Subclinical mastitis causes an increase in milk somatic cell count (SCC) and can
      lead to reduced milk production and early culling. In many countries, non-aureus
      staphylococci (NAS) is the most common bacterial finding in subclinical mastitis
      of dairy cows. New methodology makes it possible to identify NAS species, but
      knowledge about the epidemiology is limited. The objective of this project was to
      improve advisory services for mastitis control by investigating associations
      between NAS and SCC, milk production, and persistence of intramammary infections
      (IMI). Farmers who had sent milk samples to the Swedish National Veterinary
      Institute (Uppsala, Sweden) were asked to participate if NAS was identified in
      the samples. Participating farmers were asked to resample all udder quarters of
      the cow once within 1 mo. Regression models were used to investigate associations
      between NAS and cow factors, udder quarter California mastitis test and SCC, and
      persistence of IMI. Associations with cow composite milk yield and SCC were also
      investigated. In total, 671 cows from 201 herds were enrolled in the study, and
      19 NAS species were identified, of which the 4 most common were Staphylococcus
      epidermidis, Staphylococcus simulans, Staphylococcus chromogenes, and
      Staphylococcus haemolyticus. Persistent IMI was more common in udder quarters
      with Staphylococcus hyicus and S. simulans and less common in those with
      Staphylococcus saprophyticus IMI. beta-Lactamase production by the different NAS
      species varied from 0 to 100%. There was a significant association between NAS
      species and California mastitis test and SCC of udder quarters, and this varied
      depending on parity. The cow composite milk SCC at the test milking before the
      initial sample was taken differed significantly with NAS species, but not at the
      subsequent test milking. Milk yield-at the test milking before or after the
      initial sample-did not differ significantly for NAS species. There were no
      significant associations between milk yield or SCC and persistent NAS IMI. In
      conclusion, the NAS species affects SCC and persistent IMI differently but not
      milk yield.

PMID- 29174144
TI  - Factors associated with herd bulk milk composition and technological traits in
      the Italian dairy industry.
AB  - The aim of the present study was to investigate sources of variation of milk
      composition and technological characteristics routinely collected in field
      conditions in the Italian dairy industry. A total of 40,896 bulk milk records
      from 620 herds and 10 regions across Italy were analyzed. Composition traits were
      fat, protein, and casein percentages, urea content, and somatic cell score; and
      technological characteristics were rennet coagulation time, curd firming time,
      curd firmness 30 min after rennet addition to milk, and titratable acidity. Data
      of herd bulk milks were analyzed using a model that included fixed effects of
      region, herd nested within region, and season of milk analysis. An average good
      milk quality was reported in the dairy industry (especially concerning fat,
      protein, and casein percentages), and moderate to high correlations between
      composition and technological traits were observed. All factors included in the
      statistical model were significant in explaining the variation of the studied
      traits except for region effect in the analysis of casein and somatic cell score.
      Northeast and central-southern Italian regions showed the best performance for
      composition and technological features, respectively. Traits varied greatly
      across regions, which could reflect differences in herd management and
      strategies. Overall, less suitable milk for dairy processing was observed in
      summer. Results of the present study suggested that a constant monitoring of
      technological traits in the dairy industry is necessary to improve production
      quality at herd level and it may be a way to segregate milk according to its
      processing characteristics.

PMID- 29174145
TI  - Using video microscopy to improve quantitative estimates of protozoal motility
      and cell volume.
AB  - The objective of this study was to apply digital imaging to improve
      quantification of rumen protozoal biomass and distinguish treatment differences
      in cell motility and volume among ruminal protozoa. Observations of protozoa in
      rumen fluid treated with essential oils (CinnaGar, CIN; Provimi North America,
      Brookville, OH) or an ionophore (monensin, MON) indicated possible cell
      shrinkage. We hypothesized that MON would decrease protozoal motility and
      interact with CIN on cell volume. In addition, we hypothesized that analysis of
      still frames from video of swimming protozoa would improve volume prediction
      accuracy. Flocculated rumen fluid was incubated in batch culture dosed with N
      free feed only (control), MON, CIN, or a combination of MON+CIN. Samples were
      taken at 0, 3, or 6 h post-treatment and wet-mounted on a microscope fitted with
      a high-definition camera. At 3 h post-inoculation, there was a treatment
      interaction for average speed such that CIN attenuated the effect of MON, with
      treatment means of 243, 138, 211, and 183 um/s for control, MON, CIN, and
      MON+CIN, respectively. At 6 h post-inoculation, MON decreased average speed by
      79.2 um/s compared with the main effect mean without MON. We measured both
      minimum and maximum diameters (depth and width, respectively) perpendicular to
      the longitudinal axis of swimming protozoa, yielding a 3-dimensional estimate of
      protozoal volume. The ellipsoid formula (4/3)piabc, where a = 1/2 length, b = 1/2
      width, and c = 1/2 depth, was compared with previously published volume
      estimations using genera-specific coefficients (genera-specific coefficient *
      length * width2). Residuals (genera-specific coefficients - ellipsoid) were
      plotted against predicted (ellipsoid) and centered to the mean (Xi-x-) to
      evaluate both mean and slope biases. For Entodinium spp., Y = 0.248 (+/-0.037)
      (Xi - 7.98 * 104) + 1.97 * 104 (+/-1.48 * 103); n = 100; r2 [coefficient of
      determination (squared correlation coefficient)] = 0.31, with significant slope
      and mean biases. For family Isotrichidae, Y = -0.124 (+/-0.068) (Xi - 2.54 * 106)
      - 1.21 * 104 (+/-4.86 * 104); n = 32; r2 = 0.10, where slope tended to be
      different from zero but with no mean bias. For Epidinium spp., Y = 0.375 (+/
      0.056) (Xi - 2.45 * 105) + 6.65 * 104 (+/-0.28 * 104); n = 64; r2 = 0.43, with
      both mean and slope biases. The present regression analyses demonstrate that the
      genera-specific coefficient-based method more likely overestimates volume for
      Entodinium and Epidinium than for the teardrop-shaped Isotrichidae. Based on
      simulations derived from previous literature reporting treatments that depress
      protozoal populations or among-animal changes in protozoal population structures,
      our proposed ellipsoid method offers potential to advance the prediction of
      treatment effects on protozoal volume and to shift focus from the number of cells
      present to the diversity, function, and biomass of protozoa under various
      treatment conditions.

PMID- 29174146
TI  - Characteristics of feed efficiency within and across lactation in dairy cows and
      the effect of genetic selection.
AB  - The objective of the present study was to investigate the phenotypic inter- and
      intra-relationships within and among alternative feed efficiency metrics across
      different stages of lactation and parities; the expected effect of genetic
      selection for feed efficiency on the resulting phenotypic lactation profiles was
      also quantified. A total of 8,199 net energy intake (NEI) test-day records from
      2,505 lactations on 1,290 cows were used. Derived efficiency traits were either
      ratio based or residual based; the latter were derived from least squares
      regression models. Residual energy intake (REI) was defined as NEI minus
      predicted energy requirements based on lactation performance; residual energy
      production (REP) was defined as net energy for lactation minus predicted energy
      requirements based on lactation performance. Energy conversion efficiency was
      defined as net energy for lactation divided by NEI. Pearson phenotypic
      correlations among traits were computed across lactation stages and parities, and
      the significance of the differences was determined using the Fisher r-to-z
      transformation. Sources of variation in the feed efficiency metrics were
      investigated using linear mixed models, which included the fixed effects of
      contemporary group, breed, parity, stage of lactation, and the 2-way interaction
      of parity by stage of lactation. With the exception of REI, parity was associated
      with all efficiency and production traits. Stage of lactation, as well as the 2
      way interaction of parity by stage of lactation, were associated with all
      efficiency and production traits. Phenotypic correlations among the efficiency
      and production traits differed not only by stage of lactation but also by parity.
      For example, the strong phenotypic correlation between REI and energy balance
      (EB; 0.89) for cows in parity 3 or greater and early lactation was weaker for
      parity 1 cows at the same lactation stage (0.81), suggesting primiparous cows use
      the ingested energy for both milk production and growth. Nonetheless, these
      strong phenotypic correlations between REI and EB suggested negative REI animals
      (i.e., more efficient) are also in more negative EB. These correlations were
      further supported when assessing the effect on phenotypic performance of animals
      genetically divergent for feed intake and efficiency based on parental average.
      Animals genetically selected to have lower REI resulted in cows who consumed less
      NEI but were also in negative EB throughout the entire lactation. Nonetheless,
      such repercussions of negative EB do not imply that selection for negative REI
      (as defined here) should not be practiced, but instead should be undertaken
      within the framework of a balanced breeding objective, which includes traits such
      as reproduction and health.

PMID- 29174147
TI  - Predicting nutrient digestibility in high-producing dairy cows.
AB  - Our objective was to determine the effects of dry matter intake (DMI), body
      weight (BW), and diet characteristics on total tract digestibilities of dry
      matter, neutral detergent fiber, and starch (DMD, NDFD, and StarchD,
      respectively) in high-producing dairy cows. Our database was composed of 1,942
      observations from 662 cows in 54 studies from Michigan, Ohio, and Georgia. On
      average, cows ate 23 +/- 4.5 kg of dry matter/d, weighed 669 +/- 79 kg, and
      produced 38 +/- 10 kg of milk/d. Diets were 31 +/- 5% neutral detergent fiber, 27
      +/- 6% starch, 2.6 +/- 1.2% fatty acids, and 17 +/- 1.4% crude protein.
      Digestibility means were 66 +/- 6, 42 +/- 11, and 93 +/- 5% for DMD, NDFD, and
      StarchD, respectively. Forage sources included corn silage, alfalfa, and grasses.
      Corn source was classified by its ruminal fermentability. Data were analyzed
      using a mixed effects model, including diet chemical composition, forage source,
      and corn source, all expressed as percentage of dry matter, except for DMI, which
      was expressed as percentage of BW (DMI%BW); location and 2-way interactions were
      fixed effects. Cow, block, period, treatment, and study were included as random
      effects. Best fitting candidate models were generated using backward and stepwise
      regression methods. Additionally, the simplest model was generated using only DMI
      and location as fixed effects and all random effects. Candidate models were cross
      validated across studies, and the resulting predictive correlation coefficients
      across studies (PC) and root mean square error of prediction (RMSEP) were
      compared by t-test. For each nutrient, the digestibility model that resulted in
      the highest PC and lowest RMSEP was determined to be the best fitting model. We
      observed heterogeneous coefficients among the different locations, suggesting
      that specific location factors influenced digestibilities. The overall location
      averaged best fitting prediction equations were: DMD = 69 - 0.83 * DMI%BW (PC =
      0.22, RMSEP = 5.39); NDFD = 53 + 0.26 * grass %DM - 0.59 * starch %DM + 3.06 *
      DMI%BW - 0.46 * DMI%BW2 (PC = 0.53, RMSEP = 9.70); and StarchD = 96 + 0.19 *
      HFERM%DM - 0.12 * starch %DM - 1.13 * DMI%BW (PC = 0.34, RMSEP = 4.77); where
      HFERM%DM is highly-fermentable corn source as percentage of DM. Our results
      confirm that digestibility is reduced as DMI increases, albeit at a lower rate
      than that reported in National Research Council. Furthermore, dietary starch
      depresses NDFD. Whereas DMD can be predicted based on DMI only, the best
      predictions for NDFD and StarchD require diet characteristics in addition to DMI.

PMID- 29174148
TI  - Short communication: Does early-life administration of a Megasphaera elsdenii
      probiotic affect long-term establishment of the organism in the rumen and alter
      rumen metabolism in the dairy calf?
AB  - Megasphaera elsdenii is a bacterial species of the rumen that can utilize lactate
      to produce butyrate, a key volatile fatty acid often implicated in driving calf
      rumen development. Because lactate is abundant in the rumen of young calves,
      administration of M. elsdenii to increase butyrate production and thus promote
      calf rumen development is an appealing possibility. The main objective of this
      study was to determine whether M. elsdenii administration to calves via oral
      drench at 14 d of age affected its long-term establishment at 70 d
      postadministration. Ruminal volatile fatty acid and lactate profiles and blood
      glucose and beta-hydroxybutyrate concentrations were also examined to determine
      potential influence on rumen metabolism. Six neonatal Holstein heifer calves were
      blocked on d 1 by body weight (41.3 +/- 1.8 kg) and total serum protein (5.23 +/-
      0.16 g/dL) and assigned to either the M. elsdenii (n = 3) or control (n = 3)
      treatment groups. On d 14, calves in the M. elsdenii group orally received 25 mL
      of a commercially available M. elsdenii suspension, whereas calves in the control
      group received 25 mL of the same product that had been autoclaved. Rumen contents
      and blood samples were collected weekly from each animal until 84 d of age. The
      oral administration of M. elsdenii at 14 d did not increase the abundance of M.
      elsdenii 70 d postdosing, alter rumen fermentation, or change blood metabolites
      associated with butyrate. These results suggest that a single administration of
      the M. elsdenii probiotic may not affect the rumen establishment of the organism.

PMID- 29174149
TI  - Plasma calcium concentrations are decreased at least 9 hours before parturition
      in multiparous Holstein-Friesian cattle in a herd fed an acidogenic diet during
      late gestation.
AB  - Calcium homeostatic mechanisms are challenged in periparturient multiparous dairy
      cattle due to the rapid transport of large amounts of calcium into the mammary
      gland associated with colostrogenesis, resulting in decreased plasma total
      calcium concentration ([Ca]). An unresolved issue is the timing of the decrease
      in plasma [Ca] relative to the time of parturition, with the consensus view being
      that plasma [Ca] does not decrease until after parturition. The objective of this
      study, therefore, was to characterize the change in plasma [Ca] over time in
      periparturient dairy cattle. Plasma and mid-stream urine samples were collected
      daily starting 3 d before calving from 104 periparturient Holstein-Friesian dairy
      cows in a herd fed an acidogenic total mixed ration during the late dry period.
      Mixed-models ANOVA and linear and multivariable regression analyses were
      conducted. Plasma [Ca] decreased in periparturient multiparous cattle (n = 70)
      but not in primiparous cattle (n = 34). Compared with mean values approximately
      72 h before parturition ([Ca] = 2.32 mmol/L), mean plasma [Ca] in multiparous
      cattle first decreased at 9 h before parturition (2.13 mmol/L) and remained
      decreased for up to 48 h after parturition, with the lowest mean value (1.87
      mmol/L) occurring at 28 h after parturition. Mean 24-h urine Ca excretion was
      calculated to decrease by 3.5 to 3.8 g in periparturient multiparous cattle.
      Regression analysis indicated that plasma [Ca] in the 12-h period before and 24-h
      period after parturition was strongly and negatively associated with age but was
      also negatively associated with milk production indices. We conclude that plasma
      [Ca] was decreased at least 9 h before parturition in multiparous dairy cattle
      fed an acidogenic diet in late gestation, and that calcium homeostasis was
      disrupted for 2 to 3 d around parturition.

PMID- 29174150
TI  - Short communication: Decreasing the dietary ratio of n-6 to n-3 fatty acids
      increases the n-3 concentration of peripheral blood mononuclear cells in weaned
      Holstein heifer calves.
AB  - Utilization of nutrients to improve overall heifer health is of interest because
      of the importance of replacement heifers to the dairy industry. The objective of
      our study was to compare the effect of supplementation of dietary n-3 and n-6
      fatty acids (FA) on FA concentrations in peripheral blood mononuclear cells
      (PBMC) of Holstein calves. Twenty-seven Holstein heifer calves (107 +/- 2.6 d of
      age; 142.6 +/- 6.5 kg of body weight) from the university research and teaching
      herd were randomly assigned to a common TMR supplemented with 1 of 3 treatments:
      Ca salts of flaxseed FA (Virtus Nutrition, Corcoran, CA) containing 35% 18:3 n-3
      (N3), Ca salts of soybean FA (Virtus Nutrition) containing 50% 18:2 n-6 (N6), or
      a 50:50 mix of N3 and N6. Treatments were supplemented with FA at 4% of dietary
      dry matter and fed for 30 d. Feed intake was recorded daily, and body weight,
      wither height, and body condition score were measured weekly throughout the
      study. On d 28 heifers were vaccinated with a Pasteurella vaccine and the
      temperature response to the vaccine was recorded. Blood was collected on d 0 and
      28 for PBMC isolation. After total lipid extraction and FA methyl ester
      preparation, FA composition of PBMC was measured. We observed no effect of
      treatment on body weight gain, body condition score change, or wither height
      change. Heifers receiving the N3 diet had a lower temperature response to
      Pasteurella challenge compared with both the mix and N6 diets. Heifers consuming
      the N3 diet had a greater content of total n-3 FA, alpha-linolenic acid, and
      eicosapentaenoic acid in PBMC compared with heifers fed the N6 and mix diets.
      Heifers receiving the N3 diet also had a lower content of total n-6 FA, linoleic
      acid, and arachidonic acid in PBMC than heifers fed the N6 and mix diets. In
      conclusion, our study determined that feeding weaned female Holstein heifers a
      diet high in n-3 FA increased concentrations of n-3 FA in PBMC.

PMID- 29174151
TI  - Meta-analysis of the effect of white clover inclusion in perennial ryegrass
      swards on milk production.
AB  - There is increased demand for dairy products worldwide, which is coupled with the
      realization that consumers want dairy products that are produced in a sustainable
      and environmentally benign manner. Forage legumes, and white clover (Trifolium
      repens L.; WC) in particular, have the potential to positively influence the
      sustainability of pasture-based ruminant production systems. Therefore, there is
      increased interest in the use of forage legumes because they offer opportunities
      for sustainable pasture-based production systems. A meta-analysis was undertaken
      to quantify the milk production response associated with the introduction of WC
      into perennial ryegrass swards and to investigate the optimal WC content of dairy
      pastures to increase milk production. Two separate databases were created. In the
      grass-WC database, papers were selected if they compared milk production of
      lactating dairy cows grazing perennial ryegrass-WC (GC) swards with that of cows
      grazing perennial ryegrass-only swards (GO). In the WC-only database, papers were
      selected if they contained milk production from lactating dairy cows grazing on
      GC swards with varying levels of WC content. Data from both databases were
      analyzed using mixed models (PROC MIXED) in SAS (SAS Institute, Cary, NC). Within
      the grass-WC database, where mean sward WC content was 31.6%, mean daily milk and
      milk solids yield per cow were increased by 1.4 and 0.12 kg, respectively,
      whereas milk and milk solids yield per hectare were unaffected when cows grazed
      GC compared with GO swards. Stocking rate and nitrogen fertilizer application
      were reduced by 0.25 cows/ha and 81 kg/ha, respectively, on GC swards compared
      with GO swards. These results highlight the potential of GC production systems to
      achieve similar levels of production to GO systems but with reduced fertilizer
      nitrogen inputs, which is beneficial from both an economic and environmental
      point of view. In the context of increased demand for dairy products, there may
      be potential to increase the productivity of GC systems by increasing fertilizer
      nitrogen use to increase stocking rate and carrying capacity while also retaining
      the benefit of WC inclusion on milk production per cow.

PMID- 29174152
TI  - Predicting omasal flow of nonammonia N and milk protein yield from in vitro
      determined utilizable crude protein at the duodenum.
AB  - This study evaluated the relationship between utilizable crude protein (uCP) at
      the duodenum estimated in vitro and omasal flow of crude protein (CP; omasal flow
      of nonammonia N * 6.25) measured in lactating dairy cows. In vivo data were
      obtained from previous studies estimating omasal digesta flow using a triple
      marker method and 15N as microbial marker. A total of 34 different diets based on
      grass and red clover silages were incubated with buffered rumen fluid previously
      preincubated with carbohydrates for 3 h. The buffer solution was modified to
      contain 38 g of NaHCO3 and 1 g of (NH4)HCO3 in 1,000 mL of distilled water.
      Continuous sampling of the liquid phase for determination of ammonia-N was
      performed at 0.5, 4, 8, 12, 24, and 30 h after the start of incubation. The
      ammonia N concentrations after incubation were used to calculate uCP. The natural
      logarithm of uCP [g/kg of dry matter (DM)] at time points 0.5, 4, 8, 12, 24, and
      30 h of incubation was plotted against time to estimate the concentration of uCP
      (g/kg of DM) at time points 16, 20, and 24 h using an exponential function. Fixed
      model regression analysis and mixed model regression analysis with random study
      effect were used to evaluate the relationships between predicted uCP (supply and
      concentration) and observed omasal CP flow and milk protein yield. Residual
      analysis was also conducted to evaluate whether any dietary factors influenced
      the relationships. The in vitro uCP method ranked the diets accurately in terms
      of total omasal CP flow (kg/d) or omasal CP flow per kilogram of DM intake. We
      also noted a close relationship between estimated uCP supply and adjusted omasal
      CP flow, as demonstrated by a coefficient of determination of 0.87, although the
      slope of 0.77 indicated that estimated uCP supply (kg/d) was greater than the
      value determined in vivo. The linear bias with mixed model analysis indicated
      that uCP supply overestimated the difference in omasal CP flow between the diets
      within a study, an error most likely related to study differences in feed intake,
      animals, and methodology. Predicting milk protein yield from uCP supply showed a
      positive relationship using a mixed model (coefficient of determination = 0.79),
      and we observed no difference in model fit between the time points of incubation
      (16, 20, or 24 h). The results of this study indicate that the in vitro method
      can be a useful tool in evaluating protein value of ruminant diets.

PMID- 29174153
TI  - Technical note: Development and evaluation of a standard operating procedure for
      ultrasound-based measurements of teat canal dimensions in dairy cows.
AB  - The objectives were to (1) develop a standard operating procedure (SOP) for
      ultrasound-based measurements of teat canal dimensions and (2) determine the
      precision of ultrasound-based measurements of teat canal dimensions in dairy
      cows. Teat scans (n = 64) of the right hind and left front teats from 16 cows
      were obtained with a portable ultrasound device before and after machine milking.
      Teat dimensions measured were teat canal length (TCL), teat canal diameter at the
      proximal end of the teat canal (TCDPROX), teat canal diameter at the midpoint
      between the proximal and distal ends of the teat canal (TCDMID), teat canal
      diameter at the distal end of the teat canal (TCDDIS), teat end diameter at the
      midpoint between the proximal and distal ends of the teat canal (TMD), and teat
      canal cross-sectional area (TCLAREA). An SOP was developed, reviewed, and
      modified by 3 operators. Measurements were performed by the same 3 operators
      using an open source software program. To assess the effect of implemented
      modifications and the precision of ultrasound-based measurements, concordance
      correlation coefficients (CCC) were calculated to determine interoperator
      reproducibility and intraoperator repeatability. Through modifications in the
      SOP, interoperator CCC increased from 0.45 to 0.86 for TCL, from 0.14 to 0.66 for
      TCDPROX, from 0.24 to 0.66 for TCDMID, from 0.06 to 0.56 for TCDDIS, from 0.64 to
      0.91 for TMD, and from 0.17 to 0.64 for TCLAREA. Intraoperator CCC over all
      operators were 0.91 for TCL, 0.73 for TCDPROX, 0.80 for TCDMID, 0.69 for TCDDIS,
      0.94 for TMD, and 0.75 for TCLAREA. Our results indicate that measurements of
      teat canal dimensions can be conducted with satisfactory precision when following
      an SOP. Development and strict implementation of an SOP has the potential to
      decrease inadvertent variability of ultrasound-based measurements among operators
      for ultrasonographic assessment of teat dimensions.

PMID- 29174155
TI  - Genetic parameters for yield, fitness, and type traits in US Brown Swiss dairy
      cattle.
AB  - The objective of this research was to evaluate heritabilities and genetic
      correlations among yield, fitness, and type traits for US Brown Swiss cattle born
      in 2000 and later. The data set used consisted of 108,633 first through fifth
      lactation records from 45,464 cows for yield, somatic cell score (SCS), days
      open, and productive life. Approximately half of the records had observations for
      17 type traits and 41,074 had observations for milking speed. These data were
      analyzed using a series of 3 trait models. Heritability estimates of each trait
      were similar to previously reported values for both Holsteins, and Brown Swiss in
      other countries. Milk, fat, and protein yield had strong positive genetic
      correlations with productive life (0.67 to 0.71), whereas days open and SCS had
      strong negative correlations with productive life (-0.60 and -0.69,
      respectively). Days open was more unfavorably correlated with dairy form
      (angularity) than with yield. The genetic correlation of udder depth and milk
      yield was unfavorable (-0.40), whereas rear udder height (0.20) and width (0.48)
      were favorably correlated with milk yield. Udder depth had a favorable genetic
      correlation with SCS (-0.26). Type traits with the strongest genetic correlations
      with productive life were fore udder attachment, mobility, and final score (0.44,
      0.50, and 0.57, respectively). These updated genetic parameters will allow for
      improved genetic selection within the Brown Swiss breed.

PMID- 29174154
TI  - Reduced serum vitamin D concentrations in healthy early-lactation dairy cattle.
AB  - Cattle obtain vitamin D by ingestion or cutaneous exposure to UV light. Dairy
      cattle diets are frequently supplemented with vitamin D to compensate for limited
      sun exposure or during times of increased metabolic demands, such as the
      periparturient period, to maintain calcium homeostasis. Whether housing and
      supplemental vitamin D practices supply adequate amounts of vitamin D to
      optimally support the transition from gestation to lactation in dairy cattle is
      unknown. Our objective was to determine how serum vitamin D concentrations of
      dairy cows change with season, age, parity, and stage of lactation. Clinically
      healthy cows (n = 183) from 5 commercial dairies were enrolled in the study.
      Serum samples were collected at dry off, within 7 d of entering the close-up
      group, and within 7 d after calving (calving+7). Vitamin D status was determined
      by measuring serum 25-hydroxyvitamin D [25(OH)D] by radioimmunoassay. We
      performed repeated-measures mixed-effects linear regression to determine the
      effects of season, age, parity, and lactation stage (dry off, close-up, and
      calving+7) on 25(OH)D concentrations in serum. Bivariable analysis indicated that
      parity, age, and season were not associated with serum 25(OH)D concentrations.
      Sample period affected 25(OH)D concentrations, with the highest 25(OH)D levels at
      dry off (99.7 +/- 1.9 ng/mL) followed by close up (93.8 +/- 2.1 ng/mL), with the
      lowest levels at calving+7 (82.6 +/- 1.7 ng/mL). These data showed a large
      depletion of 25(OH)D in dairy cattle postpartum compared with late prepartum,
      although the biological significance of this change in these healthy cattle is
      unclear. Consumption of serum 25(OH)D by immune system functions and calcium
      homeostasis in early lactation likely caused the reduction in serum 25(OH)D
      concentrations after calving. These results suggest that determining whether
      serum 25(OH)D concentrations are associated with the incidence of transition
      period disease is an appropriate next step. Assessing the effects of enhanced
      vitamin D supplementation of cows in early lactation on postpartum diseases may
      be warranted.

PMID- 29174156
TI  - Comprehensive analysis of proteolysis during 8 months of ripening of high-cooked
      Old Saare cheese.
AB  - We applied capillary electrophoresis, liquid chromatography coupled with tandem
      mass-spectrometry (MS/MS), and ultra-performance liquid chromatography to
      determine the composition of water-insoluble and water-soluble proteinaceous
      fractions of the cheese and to study in detail the degradation of caseins during
      8 mo of ripening of Estonian high-temperature cooked hard cheese Old Saare. The
      application of high-resolution and high-accuracy MS/MS enabled identification of
      more than 3,000 small peptides, representing a fairly full casein peptidome
      containing peptides of 4 to 25 AA in length: 1,049 from beta-casein (CN), 944
      from alphaS1-CN, 813 from alphaS2-CN, and 234 from kappa-CN. The majority of beta
      CN- and alphaS1-CN-derived peptides originated from the N-terminal parts of the
      molecule, f6-93 and f1-124, respectively; peptides from alphaS2-CN arose
      predominantly from the C-terminal end f100-162. At the beginning of ripening, we
      found a relatively high amount of peptides originating from the glycomacropeptide
      part of kappa-CN, whereas peptides from para-kappa-CN prevailed during the later
      stages of ripening of the cheese. The cleavage patterns of beta-CN, alphaS2-CN,
      as well as alphaS1-CN, showed that primary proteolysis was started mainly by
      plasmin, although a low proteolytic activity of chymosin was also evident. Based
      on the analysis of cleavage sites, we observed a significant participation of
      proteolytic enzymes, including amino- and carboxypeptidases, of both mesophilic
      and thermophilic starter bacteria in further hydrolysis of oligopeptides during
      the ripening. Several new phosphopeptides were detected in the result of MS/MS
      data analysis. The profiles of the estimated concentrations of phosphopeptides
      revealed that those originating from beta-CN and alphaS1-CN accumulated during
      cheese maturation. In contrast, we did not notice any generation of
      phosphopeptides from the highly phosphorylated part of alphaS2-CN, f25-80,
      presumably due to the inaccessibility of this region to the action of plasmin and
      chymosin. The analysis of cleavage sites and the combination of principal
      component and clustering analyses provided a characterization of the complex
      dynamics of formation and degradation of peptides during cheese maturation. We
      made an attempt to obtain a comprehensive picture of proteolysis during Old Saare
      cheese ripening on the basis of the detailed peptidomic data, including also the
      less abundant peptides determined by MS/MS, and complemented by the data on
      intact caseins and free AA and reported the results in the paper.

PMID- 29174157
TI  - The contribution of previous lameness events and body condition score to the
      occurrence of lameness in dairy herds: A study of 2 herds.
AB  - It has been demonstrated that low body condition and previous occurrence of
      lameness increase the risk of future lameness in dairy cows. To date the
      population attributable fraction (PAF), which provides an estimate of the
      contribution that a risk factor makes toward the total number of disease events
      in a population, has not been explored for lameness using longitudinal data with
      repeated measures. Estimation of PAF helps to identify control measures that
      could lead to the largest improvements on-farm. The aim of this study was to use
      longitudinal data to evaluate the proportion of lameness that could be avoided in
      2 separate herds (2 populations) through (1) reduced recurrence of previous
      lameness events, (2) and moving body condition score (BCS) into more optimal
      ranges. Data were obtained from 2 UK dairy herds: herd A, a 200-cow herd with 8
      yr of data from a total of 724 cows where lameness events were based on weekly
      locomotion scores (LS; 1 to 5 scale), and herd B, a 600-cow herd with data
      recorded over 44 mo from a total of 1,040 cows where treatment of clinical cases
      was used to identify lameness events. The PAF for categories of BCS were
      estimated using a closed equation appropriate for multiple exposure categories.
      Simulation models were used to explore theoretical scenarios to reflect changes
      in BCS and recurrence of previous lameness events in each herd. For herd A, 21.5%
      of the total risk periods (cow-weeks) contained a lameness event (LS 3, 4, or 5),
      96% of which were repeat events and 19% were recorded with BCS <2 (3 wk
      previously; 0 to 5 scale). When lameness events were based on 2 consecutive weeks
      of LS 4 or 5, 4% of risk periods were recorded as lame, of which 89.5% were
      repeat events. For herd B, 16.3% of the total risk periods (consecutive 30 d)
      contained a lameness event (72.6% were repeat events) and 20% were recorded with
      BCS <=2 (0 to 120 d previously). The median PAF for all previous lameness was
      between 79 and 83% in the 2 herds. Between 9 and 21% of lameness events could be
      attributed to previous lameness occurring >16 wk before a risk period. The median
      PAF estimated for changes in BCS were in the region of 4 to 11%, depending on
      severity of lameness. Repeated bouts of lameness made a very large contribution
      to the total number of lameness events. This could either be because certain cows
      are initially susceptible and remain susceptible, due to the increased risk
      associated with previous lameness events, or due to interactions with
      environmental factors. This area requires further research.

PMID- 29174158
TI  - Symposium review: Lipids as regulators of conceptus development: Implications for
      metabolic regulation of reproduction in dairy cattle.
AB  - Pregnancy losses are substantial in dairy cattle and threaten reproductive
      efficiency. A substantial proportion of these losses occur during early stages of
      conceptus development, including the elongation phase. Elongation of the
      preimplantation conceptus is a prerequisite for maternal recognition,
      implantation, and survival of pregnancy. The onset of elongation occurs when
      concentrations of lipids in endometrial epithelial cells are increased, and it
      requires substantial coordination of lipid metabolism by conceptus cells. The
      nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      seems to have a central role in coordinating gene expression in trophectoderm
      cells at the onset of elongation, particularly of genes involved in lipid
      metabolism. Numerous fatty acids are natural ligands of PPARgamma and their
      concentrations in the histotroph are likely important to PPARgamma activity and
      its downstream effects on conceptus biology. Changes in concentration or
      composition of fatty acids in the histotroph could alter conceptus development.
      Inflammatory diseases and excessive loss of body reserves are prevalent problems
      in postpartum dairy cows and represent important risk factors for early pregnancy
      loss in the subsequent breeding period. Although cows affected by these
      conditions likely have reduced developmental capacity of oocytes, embryo transfer
      studies indicate that impaired uterine environment also contributes to their
      subfertility. Long-lasting effects of these conditions on energy and lipid
      homeostasis might alter composition of the histotroph and could help explain
      developmental failures occurring during conceptus formation attributable to
      impaired uterine environment. Targeting of uterine lipid metabolism and PPARgamma
      activity during preimplantation conceptus development through prevention of
      disease and optimized feed intake postpartum and through nutraceutical diets at
      the time of breeding are potential strategies to improve pregnancy survival and
      consequently reproductive efficiency in dairy cows.

PMID- 29174159
TI  - Fluctuations in milk yield are heritable and can be used as a resilience
      indicator to breed healthy cows.
AB  - Automatic milking systems record an enormous amount of data on milk yield and the
      cow itself. These type of big data are expected to contain indicators for health
      and resilience of cows. In this study, the aim was to define and estimate
      heritabilities for traits related with fluctuations in daily milk yield and to
      estimate genetic correlations with existing functional traits, such as udder
      health, fertility, claw health, ketosis, and longevity. We used daily milk yield
      records from automatic milking systems of 67,025 lactations in the first parity
      from 498 herds in the Netherlands. We defined 3 traits related to the number of
      drops in milk yield using Student t-tests based on either a rolling average (drop
      rolling average) or a regression (drop regression) and the natural logarithm of
      the within-cow variance of milk yield (LnVar). Average milk yield was added to
      investigate the relationships between milk yield and these new traits. ASReml was
      used to estimate heritabilities, breeding values (EBV), and genetic correlations
      among these new traits and average milk yield. Approximate genetic correlations
      were calculated using correlations between EBV of the new traits and existing EBV
      for health and functional traits correcting for nonunity reliabilities using the
      Calo method. Partial genetic correlations controlling for persistency and average
      milk yield and relative contributions to reliability were calculated to
      investigate whether the new traits add new information to predict fertility,
      health, and longevity. Heritabilities were 0.08 for drop rolling average, 0.06
      for drop regression, and 0.10 for LnVar. Approximate genetic correlations between
      the new traits and the existing health traits differed quite a bit, with the
      strongest correlations (-0.29 to -0.52) between LnVar and udder health, ketosis,
      persistency, and longevity. This study shows that fluctuations in daily milk
      yield are heritable and that the variance of milk production is best among the 3
      fluctuations traits tested to predict udder health, ketosis, and longevity. Using
      the residual variance of milk production instead of the raw variance is expected
      to further improve the trait to breed healthy, resilient, and long-lasting dairy
      cows.

PMID- 29174160
TI  - Effects of replacement of late-harvested grass silage and barley with early
      harvested silage on ruminal digestion efficiency in lactating dairy cows.
AB  - The objective of this experiment was to quantify the effects of graded
      replacement of late-harvested grass silage and barley with early-harvested silage
      on nutrient digestion and rumen fermentation. Four experimental diets were fed to
      4 multiparous rumen-cannulated Nordic Red cows in 4 * 4 Latin square design with
      21-d periods. Dietary treatments consisted of late-cut grass silage (LS) and
      rolled barley, which was gradually replaced with early-cut grass silage [ES; 0,
      33, 67, and 100% of the forage component (ES + LS) of the diet]. With increased
      proportion of ES in the diet, the proportion of barley decreased from 47.2 to
      26.6% on a dry matter basis. Early- and late-cut silages were harvested at 2-wk
      intervals (predicted concentrations of metabolizable energy 11.0 and 9.7 MJ/kg of
      dry matter). The 4 diets were formulated to support the same milk production.
      Nutrient flows were quantified using omasal sampling technique applying the
      triple-marker method (Cr, Yb, and indigestible neutral detergent fiber) and 15N
      as a microbial marker. Feed intake decreased with graded replacement of LS and
      barley with ES, but milk production was not influenced by diet. Digestibility of
      nutrients improved with graded addition of ES in the diet with the greatest
      difference observed in digestibility of neutral detergent fiber (NDF) and
      potentially digestible NDF (pdNDF). The results suggested that improved cell wall
      digestibility with graded level of ES in the diet was partly related to higher
      intrinsic digestibility of ES than LS, and partly due to negative associative
      effects with an increased proportion of LS and barley in the diet. Efficiency of
      microbial N synthesis was not influenced by the diet, but ruminal protein
      degradability increased with ES in the diet. Rumen fermentation pattern was not
      affected by the diet despite large difference in the profile of dietary
      carbohydrates. Rumen pool size of NDF and pdNDF, and ruminal turnover time of NDF
      decreased with graded addition of ES in the diet, whereas digestion rate of pdNDF
      improved. The results of this study indicate that increased CH4 yield in a
      parallel production study with graded addition of ES in the diet were more
      related to greater ruminal and total digestibility of organic matter than to the
      changes in rumen fermentation pattern.

PMID- 29174161
TI  - A Role for Fc-Mediated Humoral Immunity in Reducing HIV Transmission Rates
      between HIV Serodiscordant Heterosexual Couples.

PMID- 29174162
TI  - Moving skills training closer to application: In-rotation skills curriculum is
      feasible and effective.
AB  - PURPOSE: Using simulation can help surgical trainees acquire surgical skills but
      at the expense of clinical learning time. We postulate an in-rotation skills
      curriculum is feasible and minimizes time away from clinical experiences.
      METHODS: Surgical residents (PGY2-5) were allotted two hours of weekly protected
      time for rotation specific simulation modules that included assessment,
      mentoring, and practice. Between September 2015 and February 2016 performance
      data was collected and participants were surveyed. RESULTS: Completion rates of
      87-100% were achieved and post-test scores improved significantly, indicating
      improved performance. The survey (29/30 RR) revealed that 81.5% felt 2 hours a
      week was 'just right' and 79.3% agreed or strongly agreed the in-rotation aspect
      was a benefit. Improved confidence in the OR was reported by 86.2% of residents
      Intra-operative skill was self-assessed as improved in 79.3%. CONCLUSION: In
      rotation skills curriculum with high completion rates is feasible and allows
      training in close proximity to clinical application. Performance in the simulated
      environment significantly improved with corresponding improvements in confidence
      and self-assessed skill in the operating room.

PMID- 29174163
TI  - Cancer history: A predictor of IPMN subtype and dysplastic status?
AB  - INTRODUCTION: The aim of this study was to determine the association of PMH and
      FH of pancreatic (PDAC) and non-pancreatic cancers with IPMN malignant risk.
      METHODS: A retrospective review of a prospective database of IPMN patients
      undergoing resection was performed to assess FH and PMH. RESULTS: FH of PDAC was
      present in 13% of 362 included patients. Of these, 8% had at least one first
      degree relative (FDR) with PDAC. The rate of PDAC positive FH in non-invasive
      versus invasive IPMN patients was 14% and 8%, respectively (p = 0.3). In main
      duct IPMN patients, FH (44%) and PMH of non-pancreatic cancer (16%) was higher
      than that seen in branch duct IPMN (FH 29%; PMH 6%; p = 0.004 and 0.008).
      CONCLUSIONS: FH of PDAC is not associated with IPMN malignant progression. FH and
      PMH of non-pancreatic cancer is associated with main duct IPMN, the subtype with
      the highest rate of invasive transformation.

PMID- 29174164
TI  - Resident attitudes and compliance towards robotic surgical training.
AB  - BACKGROUND: Adoption of robotics in general surgery has expanded but there is no
      mandatory national standardized curriculum for general surgery residents (GSR).
      METHODS: A survey was administered to all GSRs in 2014 addressing future practice
      and robotic experience. A non-mandatory robotic curriculum was available for
      residents to train. Compliance was assessed. In 2016, the same survey was re
      administered. Barriers to completing the curriculum were identified. RESULTS:
      Interest in improving robotic skills remained high (2014 = 97.8% vs 2016 = 95.9%,
      p = 0.608), and the majority planned to incorporate robotics into future practice
      (77.8% vs 69.4%; p = 0.358). Only 11 residents (18%) voluntarily completed the
      curriculum while 36 (60%) started but did not complete. A trend toward increased
      procedure participation was seen (60.0%-77.6%, p = 0.066). The perceived barriers
      to completion of the curriculum were length of time required (80%) and lack of
      access to a simulator (60%). CONCLUSIONS: A structured robotic training
      curriculum that is non-mandatory is insufficient in helping residents gain
      fundamental robotic skills.

PMID- 29174165
TI  - The negative impact of understaging rectal cancer patients.
AB  - BACKGROUND: Neo-adjuvant chemoradiation followed by surgery and adjuvant therapy
      is standard treatment of clinical node positive rectal cancer. Understaging leads
      to delay in treatment with possible detrimental results. This study analyses
      effects of understaging stage III rectal cancer on long-term outcomes. METHODS: A
      consecutive series of patients, operated on in MGH between 2004 and 2015 was
      included. Outcomes of non-neoadjuvantly treated clinical stage I patients who
      turned out to have pathological stage III disease and neoadjuvantly treated
      clinical stage III patients were retrospectively reviewed. The latter group was
      subdivided into patients who had persistent nodal disease (ypN+) and patients
      without positive lymph nodes after neoadjuvant treatment (ypN0). RESULTS: Of the
      204 included patients, 30 had unexpected nodal disease on pathology. Clinical
      stage I-patients had higher rates of local recurrence, and rectal cancer and
      overall mortality than ypN0-patients. CONCLUSION: Understaging stage III rectal
      cancer led to poorer oncologic outcomes, when compared to patients without
      positive lymph nodes on pathology after neoadjuvant. Future research should focus
      on identifying patients with treatment susceptible lymph node involvement.

PMID- 29174166
TI  - Pre-simulation orientation for medical trainees: An approach to decrease anxiety
      and improve confidence and performance.
AB  - BACKGROUND: We assessed the effect of basic orientation to the simulation
      environment on anxiety, confidence, and clinical decision making. METHODS: Twenty
      four graduating medical students participated in a two-week surgery preparatory
      curriculum, including three simulations. Baseline anxiety was assessed pre
      course. Scenarios were completed on day 2 and day 9. Prior to the first
      simulation, participants were randomly divided into two groups. Only one group
      received a pre-simulation orientation. Before the second simulation, all students
      received the same orientation. Learner anxiety was reported immediately preceding
      and following each simulation. Confidence was assessed post-simulation.
      Performance was evaluated by surgical faculty. RESULTS: The oriented group
      experienced decreased anxiety following the first simulation (p = 0.003); the
      control group did not. Compared to the control group, the oriented group reported
      less anxiety and greater confidence and received higher performance scores
      following all three simulations (all p < 0.05). CONCLUSIONS: Pre-simulation
      orientation reduces anxiety while increasing confidence and improving
      performance.

PMID- 29174167
TI  - Progress in the diagnosis and management of adolescent endometriosis: an opinion.
AB  - Increasing evidence indicates that early onset endometriosis (EOE), starting
      around menarche or early adolescence, may have an origin different from the adult
      variant, originating from neonatal uterine bleeding (NUB). This implies seeding
      of naive endometrial progenitor cells into the pelvic cavity with NUB; these can
      then activate around thelarche. It has its own pathophysiology, symptomatology
      and risk factors, warranting critical management re-evaluation. It can also be
      progressive, endangering future reproductive capacity. This variant seems to be
      characterized by the presence of ovarian endometrioma. Today, the diagnosis of
      endometriosis in young patients is often delayed for years; if rapidly
      progressive, it can severely affect pelvic organs, even in the absence of serious
      symptoms. Given the predicament, great attention must be paid to symptomatology
      that is often non-specific, justifying a search for new, simple, non-invasive
      markers of increased risk. Better use of modern imaging techniques will aid
      considerably in screening for the presence of EOE. Traditional laparoscopy should
      be limited to cases in which imaging gives rise to suspicion of severity and a
      stepwise, minimally invasive approach should be used, followed by medical
      treatment to prevent recurrence. In conclusion, EOE represents a condition
      necessitating early diagnosis and stepwise management, including medical
      treatment.

PMID- 29174168
TI  - Advanced glycation end product concentrations in follicular fluid of women
      undergoing IVF/ICSI with a GnRH agonist protocol.
AB  - The accumulation of advanced glycation end products (AGE) is associated with
      ovarian dysfunction. This study examines whether the accumulation of AGE in
      follicular fluid affects ovarian responsiveness and embryo quality during
      IVF/intracytoplasmic sperm injection (IVF/ICSI) with a gonadotrophin-releasing
      hormone (GnRH) agonist protocol. The levels of AGE in follicular fluid were
      measured in 127 women undergoing IVF/ICSI in GnRH agonist cycles. Plasma hormones
      were also measured. Embryos were graded using standard approaches. There were
      inverse associations between follicular fluid AGE concentration and number of
      oocytes retrieved, number of fertilized oocytes, number of high-quality embryos,
      fertilization rate and high-quality embryo rate, adjusted for potential
      confounders. AGE concentration in follicular fluid was significantly higher in
      women with an ovarian response below the target (<7 oocytes) compared with those
      reaching the target (7-15 oocytes) or above the target (>15 oocytes). The cut-off
      value of 15.3 ug/ml for follicular fluid AGE showed 84.6% sensitivity and 55.5%
      specificity in evaluating the response to ovarian stimulation as below the
      target. The results suggest that ovarian responsiveness and embryo quality are
      related to intraovarian exposure to AGE.

PMID- 29174169
TI  - Severe camptocormia due to myositis of paraspinal muscles as an early
      manifestation of Parkinson's disease.

PMID- 29174170
TI  - Kinsbourne syndrome associated with cryptococcosis infection.

PMID- 29174171
TI  - Helicobacter pylori infection is associated with an increased risk of Parkinson's
      disease: A population-based retrospective cohort study.
AB  - BACKGROUND: Several studies have evaluated the association of Parkinson's disease
      with Helicobacter pylori (HP) infection, although no cohort studies have
      evaluated this association among the general population. OBJECTIVE: This study
      aimed to investigate the risk of Parkinson's disease after HP infection in the
      general Taiwanese population. METHODS: This study of Taiwanese health insurance
      data (2000-2012) evaluated 9105 cases of HP infection and 9105 controls matched
      with propensity scoring. Univariate and multivariate Cox proportional hazards
      regression models were used to assess the risk of subsequent Parkinson's disease.
      RESULTS: We observed 64 cases of Parkinson's disease in the HP infection group
      (1.7/1000 person-years), and 25 cases in the control group (0.7/1000 person
      years). Overall, there was a significantly higher risk of Parkinson's disease in
      the HP infection group (adjusted hazard ratio [aHR]: 2.29, 95% confidence
      interval [CI]: 1.44-3.66). HP infection was significantly associated with an
      increased risk of Parkinson's disease among individuals who were >=60 years old
      (aHR: 2.53, 95% CI: 1.47-4.35), but not among those <60 years old (aHR: 1.86, 95%
      CI: 0.69-4.98). Furthermore, HP infection was associated with an increased risk
      of Parkinson's disease among both men (aHR: 2.14, 95% CI: 1.15-3.96) and women
      (aHR: 2.84, 95% CI: 1.37-5.89). Nonetheless, eradication therapy was not
      significantly associated with the risk of Parkinson's disease (aHR: 1.07, 95% CI:
      0.63-1.82). CONCLUSION: Although HP infection was associated with an increased
      risk of Parkinson's disease, eradication therapy did not ameliorate this
      association. Further research is needed to explore the underlying biological
      mechanisms.

PMID- 29174172
TI  - Juvenile-onset parkinsonism with pyramidal signs due to compound heterozygous
      mutations in the F-Box only protein 7 gene.
AB  - BACKGROUND: Juvenile-onset parkinsonism is often caused by genetic factors.
      Mutations in several autosomal genes, including the F-box only protein 7 (FBXO7)
      gene, have been found in patients suffering from juvenile-onset parkinsonism with
      pyramidal signs. Only five types of FBXO7 mutations have been described. Here, we
      present a case report about a Chinese patient presenting with juvenile-onset
      parkinsonism likely caused by FBXO7 mutations. METHODS: The patient was a 32-year
      old Chinese male. DNA samples were extracted from the patient and his parents.
      Exons in parkinsonism-related genes were amplified and sequenced. RESULTS: The
      patient began experiencing a progressive involuntary tremor in his left hand at
      16 years of age, which was followed by the development of gait dysfunction,
      dysarthria, and rapid eye movement sleep behavior disorder. A neurological
      examination of the patient revealed cogwheel rigidity, bradykinesia, static and
      postural tremor and bilateral Babinski signs. The patient responded to
      dopaminergic therapies but was affected by psychiatric side effects. Further
      genetic analysis of the patient and his parents revealed compound heterozygous
      mutations of the FBXO7 gene (NM_012179.3) in the patient (a nonsense c.1408G > T
      (p.E470X) mutation and a missense c.152A > G (p.N51S) mutation coming from the
      patient's mother and father, respectively). CONCLUSIONS: This is the first case
      harboring FBXO7 mutations that presented with juvenile-onset parkinsonism in the
      Chinese population.

PMID- 29174174
TI  - Significant association of rheumatoid arthritis-related inflammatory markers with
      non-surgical periodontal therapy.
AB  - BACKGROUND/PURPOSE: Chronic periodontitis (CP) and rheumatoid arthritis (RA) are
      the most common chronic inflammatory diseases and their immunopathogenesis is
      similar. The aim of this study was to evaluate the effect of non-surgical
      periodontal treatment on the serum levels of RA-related inflammatory markers in
      patients with chronic periodontitis. METHODS: Thirty-one Taiwanese adults with CP
      were included. Demographics and periodontal parameters, including probing depth,
      clinical attachment level, and number of remaining teeth in the oral cavity, were
      recorded. All subjects received non-surgical periodontal treatment such as
      scaling and subgingival root planing. Serum samples were collected before and
      after the treatment. Serum levels of anti-citrullinated protein antibodies
      (ACPA), rheumatoid factor, tumor necrosis factor-alpha (TNF-alpha), C-reactive
      protein, interleukin-1beta (IL-1beta), and Interleukin-6 (IL-6) were measured
      using an enzyme-linked immunosorbent assay. RESULTS: Non-surgical periodontal
      treatment significantly reduced the serum ACPA (p = 0.015) and TNF-alpha levels
      (p = 0.026) in CP patients, particularly in patients with generalized CP.
      Furthermore, there was a significant and positive correlation between the number
      of extracted teeth and the reduction in the serum ACPA (p = 0.05) and IL-1beta
      levels (p = 0.029) after non-surgical periodontal treatment. CONCLUSION: Non
      surgical periodontal therapy may aid in the control of RA-related inflammatory
      markers in patients with CP. A large-scale study with well-defined populations is
      needed to clarify the benefit of non-surgical periodontal therapy.

PMID- 29174173
TI  - Spatiotemporal Control of Acetyl-CoA Metabolism in Chromatin Regulation.
AB  - The epigenome is sensitive to the availability of metabolites that serve as
      substrates of chromatin-modifying enzymes. Links between acetyl-CoA metabolism,
      histone acetylation, and gene regulation have been documented, although how
      specificity in gene regulation is achieved by a metabolite has been challenging
      to answer. Recent studies suggest that acetyl-CoA metabolism is tightly regulated
      both spatially and temporally to elicit responses to nutrient availability and
      signaling cues. Here we discuss evidence that acetyl-CoA production is
      differentially regulated in the nucleus and cytosol of mammalian cells. Recent
      findings indicate that acetyl-CoA availability for site-specific histone
      acetylation is influenced through post-translational modification of acetyl-CoA
      producing enzymes, as well as through dynamic regulation of the nuclear
      localization and chromatin recruitment of these enzymes.

PMID- 29174175
TI  - Imaging appearances of hepatic tuberculosis: experience with 12 patients.
AB  - AIM: To review computed tomography (CT), ultrasound (US), magnetic resonance
      cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography
      (ERCP) and percutaneous transhepatic cholangiogram (PTC) appearances and their
      diagnostic value in hepatic tuberculosis. MATERIALS AND METHODS: The imaging
      studies for 12 patients with biopsy-proven hepatic tuberculosis from January 2012
      till March 2014 were reviewed retrospectively. These cases were confirmed via
      ultrasound-guided biopsy. RESULTS: The patients were aged 24-72 years. Four
      patients had parenchymal tuberculosis only and eight patients had mixed
      parenchymal and biliary duct involvement. The parenchymal tuberculosis patients
      showed poorly enhancing, hypodense nodules on CT with central calcification and
      adjacent dilated intrahepatic ducts. Most patients had multiple lesions except
      for two patients with a single lesion. The size of the lesions ranged from 0.5 to
      6 cm. Seven patients with biliary duct involvement showed a hilar strictures
      involving the intrahepatic ducts and common bile duct. Nine of the patients
      showed hilar stricture with atrophy of the ipsilateral lobe of the liver and
      compensatory hypertrophy of the contralateral lobe. Hepatolithiasis was seen in
      five patients. Tuberculous lung involvement was seen in seven patients.
      CONCLUSION: The presence of calcified and hypodense nodules with biliary duct
      dilatation associated with lobar atrophy were the most consistent features of
      hepatic tuberculosis, especially in the presence of active lung disease.

PMID- 29174176
TI  - Communicating Biotech Advances: Fiction versus Reality.
AB  - Bioscience novels use selected technologies of genetic engineering and synthetic
      biology to create entertaining stories. These novels are usually based on
      scientific knowledge, but they may arouse public concerns about technology and
      drive public reluctance to accept innovative technologies. The scientific
      community must adopt more efficient communication and transparency.

PMID- 29174177
TI  - Long-term outcomes of six patients after partial internal biliary diversion for
      progressive familial intrahepatic cholestasis.
AB  - BACKGROUND: Partial internal biliary diversion (PIBD) is an alternative approach
      for the treatment of devastating pruritus in patients with progressive familial
      intrahepatic cholestasis (PFIC). In these patients quality of life can be
      improved and progression of liver disease can be delayed while waiting for liver
      transplantation. The aim of our study was to evaluate six patients with PFIC who
      have undergone PIBD in long-term follow-up. METHODS: Retrospective review of the
      records of six patients who underwent PIBD for PFIC between 2008 and 2010 was
      conducted to evaluate age, growth, clinical and laboratory studies for long-term
      outcome. RESULTS: Serum postoperative bile acid levels were reduced from a mean
      340.1MUmol/L (range 851-105) preoperatively to a mean of 96.3MUmol/L at
      postoperative fifth year. The difference between pre- and postoperative bile acid
      levels was statistically significant (p=0.018). AST decreased from 79.1U/L (range
      43-150U/L) to 64.6U/L (range 18-172U/L), ALT decreased from 102.8U/L (range 35
      270U/L) to 84.6U/L and total bilirubin decreased from 2.9MUmol/L (range 0.35
      6.4MUmol/L) to 1.53MUmol/L (range 0.3-2.4). Again, the decrease in total
      bilirubin levels was significant (p=0.043). Pruritus was diminished from a mean
      of +4 (range 4-4) preoperatively to a mean of +2 (4-0). One patient who underwent
      liver transplantation owing to relapsing pruritus died from postoperative sepsis
      in the early postoperative period at the fifth year after PBID. Five symptom-free
      patients have not required liver transplantation at a mean period of 6.1+/
      0.83years (5.1-7.0years) follow-up. CONCLUSION: PBID is an effective surgical
      procedure in the long-term and can delay the need for liver transplantation in
      children with PFIC by reducing jaundice and pruritus.

PMID- 29174178
TI  - Radiation burden of pediatric ultrasound-guided percutaneous central venous
      access devices: A prospective cohort study.
AB  - : Permanent central venous access is essential for the management of many
      pediatric patients. Knowing the amount of ionizing radiation used during the
      insertion of these devices is important. Our aim was to identify the radiation
      used in percutaneous insertion of central venous access devices, and to correlate
      radiation exposure to patient weight. METHODS: Data was prospectively collected
      during a 12-month period from August 2015 to August 2016 on all ultrasound-guided
      percutaneous central venous access device insertions. An image intensifier was
      used in all insertions with data on radiation dose and screening time extracted,
      when available. The total radiation dose was measured in mGym2 and the total
      radiation time in seconds. A p-value <0.05 was used to denote statistical
      significance. RESULTS: A total of 145 central venous access devices were inserted
      (82 portacaths, 43 double lumen lines, 16 single lumen lines and 4 hemocaths) in
      127 patients (Median Age: 5.5years (Range 0-17); Median Weight 21kg (Range 1.9
      100)) with 15 patients requiring multiple insertions over the course of the
      study. Of these, 88 had data captured for total radiation dose and time used and
      a further 23 had screening time only recorded. Median radiation dose was 0.00599
      mGym2 (range 0.000543-0.148) with a median fluoroscopic screening time of 18s
      (range 2-479). Median dose was higher for children <10kg compared to larger
      children, 0.00661 mGym2 (range 0.00202-0.0468) versus 0.005715 mGym2 (range
      0.000543-0.148) respectively. Left-sided internal jugular vein (IJV) insertions
      also had a higher median radiation dose of 0.0091 mGym2 (range 0.00142-0.148
      mGym2) versus 0.005245 mGym2 (range 0.000543-0.0285 mGym2) for right-sided IJV
      insertions. CONCLUSION: The radiation burden to children from percutaneous
      ultrasound-guided central venous access device insertions is small, in the order
      of that received during a chest radiograph. Weight<10kg and access of the left
      IJV are associated with receiving higher doses. STUDY TYPE: Cohort Study (Level
      of Evidence: II).

PMID- 29174179
TI  - Erratum to "Cell death pathways of particulate matter toxicity" Chemosphere 188C
      (2017) 32-48.

PMID- 29174180
TI  - [Occupational hazards due to exposure to waste anesthetic gases].

PMID- 29174181
TI  - Overall survival in MERiDiAN, a double-blind placebo-controlled randomised phase
      III trial evaluating first-line bevacizumab plus paclitaxel for HER2-negative
      metastatic breast cancer.

PMID- 29174182
TI  - Corrigendum to "Loss of tight junction plaque molecules in breast cancer tissues
      is associated with a poor prognosis in patients with breast cancer" [Eur J Cancer
      40 (18) (2004) 2717-2725].

PMID- 29174183
TI  - Speech induced cervical dystonia: An unusual task specific dystonia.

PMID- 29174184
TI  - Competitive interaction between chronic obstructive pulmonary disease and CHA2DS2
      VASc score in predicting incident atrial fibrillation.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of
      morbidity and mortality, and an emerging risk factor for atrial fibrillation
      (AF). CHADS2 and CHA2DS2-VASc scores are significantly associated with incident
      AF independently of other risk factors. The aim of this study was to demonstrate
      a possible interaction between COPD and CHA2DS2-VASc in predicting incident AF.
      METHODS: This observational prospective cohort study included 4322 Caucasians
      with cardiovascular risk factors, stratified by CHA2DS2-VASc score (>2 vs <2) and
      presence/absence of COPD. To detect AF appearance, patients underwent, every
      6months, physical examination, standard 12-lead electrocardiogram and routine
      laboratory tests. RESULTS: COPD prevalence was significantly higher in patients
      with CHA2DS2-VASc>=2 vs CHA2DS2-VASc<2 category (13.3% vs 10.5%, P=0.009). During
      the follow-up, 589 cases of AF were documented (3.8 events/100 patients-year).
      COPD+ showed a significantly higher incidence of AF vs COPD- patients (17.4 vs
      8.4 events/100 patients-year, P<0.0001). In Cox regression models both CHA2DS2
      VASc score (HR=4.70, 95% CI=3.63-6.08) and COPD (HR=2.04, 95% CI=1.69-2.48)
      significantly predicted the incidence rate of AF; this was also confirmed
      introducing the two variables into the same Cox model. A significant competitive
      interaction between CHA2DS2-VASc and COPD was found in a Cox model in patients
      with CHA2DS2-VASc<2 (HR=8.45, 95% CI=5.20-13.74) than in those with CHA2DS2
      VASc>=2. CONCLUSIONS: COPD is an independent and strong predictor of incident AF.
      The presence of COPD increases the HR for incident AF about five times in
      patients with CHA2DS2VASc score<2, while the coexistence of a CHA2DS2Vasc
      score>=2 minimizes the prognostic significance of COPD.

PMID- 29174185
TI  - Specific motor patterns of arousal disorders in adults: a video-polysomnographic
      analysis of 184 episodes.
AB  - OBJECTIVE: To compile an objective accurate description of the motor patterns of
      adult arousal disorders (ADs). METHODS: We reviewed 59 nocturnal video
      polysomnographic (VPSG) recordings of 30 adult patients (>15 years) with a
      history of sleepwalking (SW). We scrutinized the semeiology of all 184 episodes
      recorded, classifying them into three groups according to three semeiological
      motor patterns characterized by increasing intensity and complexity: simple
      arousal movements (pattern I), characterized by head flexion/extension, head
      flexion/extension and limb movement or head flexion/extension and partial trunk
      flexion/extension; rising arousal movements (pattern II), characterized by a
      complete trunk flexion with patient sitting up in bed; and complex arousal with
      ambulatory movements (pattern III) characterized by SW. The VPSG recordings were
      compared to those of 10 healthy controls. RESULTS: AD patients presented with 169
      pattern I, 37 pattern II, and nine pattern III episodes. Pattern I developed into
      pattern II in 17 cases and into pattern II followed by pattern III in five
      patients. Pattern II developed into pattern III in four patients. Onset was
      abrupt in 55% of the episodes. Episodes lasted a mean (+/-standard deviation) of
      33 +/- 35 s. Movements tended to halt temporarily during 72% of the episodes. We
      recorded 248 movements during sleep in the healthy controls, none of whom
      presented with AD patterns. CONCLUSION: We identified three specific motor
      patterns in AD patients not previously reported and not observed in healthy
      controls. Identification of these patterns could be important for diagnosis and
      serve as the basis for a new definition of AD in adults.

PMID- 29174186
TI  - Safety and efficacy of eribulin for "real-world" older patients with metastatic
      breast cancer.

PMID- 29174187
TI  - Risk of cancer death by comorbidity severity and use of adjuvant chemotherapy
      among women with locoregional breast cancer.
AB  - OBJECTIVES: To examine the associations of comorbidity and chemotherapy with
      breast cancer- and non-breast cancer-related death. MATERIALS AND METHODS:
      Included were women with invasive locoregional breast cancer diagnosed in 2004
      from seven population-based cancer registries. Data were abstracted from medical
      records and verified with treating physicians when there were inconsistencies and
      missing information on cancer treatment. Comorbidity severity was quantified
      using the Adult Comorbidity Evaluation 27. Treatment guideline concordance was
      determined by comparing treatment received with the National Comprehensive Cancer
      Network guidelines. Kaplan-Meier method and multivariable Cox proportional
      hazards regressions were employed for statistical analyses. RESULTS: Of 5852
      patients, 76% were under 70years old and 69% received guideline concordant
      adjuvant chemotherapy. Comorbidity was more prevalent in women age 70 and older
      (79% vs. 51%; p<0.001). After adjusting for tumor characteristics and treatment,
      severe comorbidity burden was associated with significantly higher cancer-related
      mortality in older patients (Hazard Ratio [HR]=2.38, 95% CI 1.08-5.24), but not
      in younger patients (HR=1.78, 95% CI 0.87-3.64). Among patients receiving
      guideline adjuvant chemotherapy, cancer-related mortality was significantly
      higher in older patients (HR=2.35, 95% CI 1.52-3.62), and those with severe
      comorbidity (HR=3.79, 95% CI 1.72-8.33). CONCLUSIONS: Findings suggest that,
      compared to women with no comorbidity, patients with breast cancer age 70 and
      older with severe comorbidity are at increased risk of dying from breast cancer,
      even after adjustment for adjuvant chemotherapy and other tumor and treatment
      differences. This information adds to risk-benefit discussions and emphasizes the
      need for further study of the role for adjuvant chemotherapy in these patient
      groups.

PMID- 29174188
TI  - Impact of Radiation Dose Reduction in Abdominal Computed Tomography on Diagnostic
      Accuracy and Diagnostic Performance in Patients with Suspected Appendicitis: An
      Intraindividual Comparison.
AB  - RATIONALE AND OBJECTIVES: To determine the intraindividual impact of radiation
      dose reduction in abdominal computed tomography (CT) on diagnostic performance in
      patients with suspected appendicitis. MATERIALS AND METHODS: This study was
      approved by the institutional review board. Seventy-five patients who underwent
      standard contrast-enhanced abdominal CT for suspected appendicitis between 2004
      and 2009 were retrospectively included. Low-dose CT reconstructions with 75%,
      50%, and 25% of the original radiation dose level were generated by applying
      realistic reduced-dose simulation. Two blinded, independent readers assessed
      image quality, signal-to-noise ratio, and diagnostic confidence on each dataset.
      Diagnostic accuracy for detection of appendicitis and complications were
      calculated for each reader. Paired univariate tests were used to determine
      intraindividual differences. RESULTS: Among 75 subjects included in the analysis
      (57% female, mean age: 41 +/- 18 years), the prevalence of histopathologically
      confirmed appendicitis was 59%. Signal-to-noise ratio and subjective image
      quality of 50% and 25% reduced-dose CTs were significantly lower than the
      reference datasets (all P < .005). Appendicitis was correctly identified in all
      reference and low-dose datasets (sensitivity: 100%, negative predictive value:
      100%). Presence of complications was correctly detected in all reference, 75%,
      and 50% datasets, but was decreased in 25% datasets (sensitivity: 77.8% and
      negative predictive value: 97.4%). Diagnostic confidence was high for original
      and 75% datasets, but significantly lower for 50% and 25% datasets (P < .001).
      CONCLUSIONS: Our results indicate that diagnostic accuracy in abdominal CT
      acquisitions acquired at 75% and 50% of radiation dose is maintained in patients
      with suspected appendicitis, whereas further reduction of radiation exposition is
      associated with decreased diagnostic performance.

PMID- 29174189
TI  - Regional Heterogeneity of Lobar Ventilation in Asthma Using Hyperpolarized Helium
      3 MRI.
AB  - RATIONALE AND OBJECTIVES: To determine lobar ventilation patterns in asthmatic
      lungs with hyperpolarized 3He magnetic resonance imaging (HP 3He MRI). MATERIALS
      AND METHODS: Eighty-two subjects (14 normal, 48 mild-to-moderate asthma, and 20
      severe asthma) underwent HP 3He MRI, computed tomography (CT), and pulmonary
      function testing. After registering proton to 3He images, we segmented the lungs
      from proton MRI and further segmented the five lung lobes (right upper lobe
      [RUL], right middle lobe [RML], and right lower lobe [RLL]; left upper lobe and
      left lower lobe [LLL]) by referring to the lobar segmentation from CT. We
      classified the gas volume into four signal intensity levels as follows:
      ventilation defect percent (VDP), low ventilation percent, medium ventilation
      percent, and high ventilation percent. The local signal intensity variations in
      the ventilated volume were estimated using heterogeneity score (Hs). We compared
      each ventilation level and Hs measured in the whole lung and lobar regions across
      the three subject groups. RESULTS: In mild-to-moderate asthma, the RML and RUL
      showed significantly greater VDP than the two lower lobes (RLL and LLL) (P <=
      .047). In severe asthma, the pattern was more variable with the VDP in the RUL
      significantly greater than in the RLL (P = .026). In both asthma groups, the
      lower lobes (RLL and LLL) showed significantly higher high ventilation percent
      and Hs compared to the three upper lobes (all P <= .015). CONCLUSIONS: In asthma,
      the RML and RUL showed greater ventilation abnormalities, and the RLL and LLL
      were more highly ventilated with greater local heterogeneity. These findings may
      facilitate guided bronchoscopic sampling and localized airway treatment in future
      studies.

PMID- 29174190
TI  - Communicating Radiology Test Results: Are Our Phone Calls Excessive, Just Right,
      or Not Enough?
AB  - RATIONALE AND OBJECTIVES: This study aimed to determine the preferences of
      radiology and referring provider residents regarding direct communication of
      radiology test results. METHODS: This Health Insurance Portability and
      Accountability Act-compliant quality improvement effort was exempt from
      institutional review board oversight. An anonymous survey was emailed to 44
      radiology residents and 364 referring resident providers who routinely provide or
      receive direct communication of test results at our quaternary care medical
      center. The survey focused on the frequency, indication, clinical utility, and
      methods of direct communication of radiology results. Proportions were compared
      to chi-square or Fisher exact test. RESULTS: The response rates were 86% (37 of
      43) (radiology) and 41% (151 of 364) (referring providers). Approximately half of
      radiology residents (49% [18 of 37]) thought the frequency of direct verbal
      communication was excessive, and none (0 of 37) thought more communication was
      needed. In contrast, only 1.3% (2 of 151; P < .001) of referring providers felt
      the frequency was excessive, and 24% (36 of 151; P < .001) desired more. The
      majority (66% [100 of 151]) of referring providers felt phone calls from
      radiologists often or always added value beyond a timely radiology report, and
      59% (44 of 74) felt it is the radiologist's responsibility to call about abnormal
      findings. Furthermore, 83% (125 of 151) of referring providers preferred to
      receive a phone call about non-emergent unexpected findings, although preferences
      varied for various example abnormalities. For outpatients with non-emergent
      unexpected findings, most providers (90% [64 of 71]) prefer written communication
      rather than a phone call. CONCLUSIONS: Referring providers prefer direct
      communication of radiology results, even for non-urgent unexpected findings,
      whereas radiology residents prefer less direct communication and are more likely
      to consider radiologist-to-provider communication superfluous.

PMID- 29174191
TI  - Expanding the Definition of a Benign Renal Cyst on Contrast-enhanced CT: Can
      Incidental Homogeneous Renal Masses Measuring 21-39 HU be Safely Ignored?
AB  - RATIONALE AND OBJECTIVE: We aimed to determine the frequency and clinical
      significance of homogeneous renal masses measuring 21-39 Hounsfield units on
      contrast-enhanced computed tomography (CT). METHODS: Subjects 40-69 years old
      undergoing portal-venous-phase contrast-enhanced abdominal CT from January 1,
      2006 to December 31, 2010 with slice thickness <=5 mm and no prior CT or magnetic
      resonance imaging were identified (n = 1387) for this institutional review board
      approved retrospective cohort study. Images were manually reviewed by three
      radiologists in consensus to identify all circumscribed homogeneous renal masses
      (maximum of three per subject) >=10 mm with a measured attenuation of 21-39
      Hounsfield units. Exclusion criteria were known renal cancer or imaging performed
      for a renal indication. The primary outcome was retrospective characterization as
      a clinically significant mass, defined as a solid mass, a Bosniak IIF/III/IV
      mass, or extirpative therapy or metastatic renal cancer within 5 years' follow
      up. RESULTS: Eligible masses (n = 74) were found in 5% (63/1387) of subjects. Of
      those with a reference standard (n = 42), none (0% [95% CI: 0.0%-8.4%]) were
      determined to be clinically significant. CONCLUSION: Incidental renal masses on
      contrast-enhanced CT that are homogeneous and display an attenuation of 21-39
      Hounsfield units are uncommon in patients 40-69 years of age, unlikely to be
      clinically significant, and may not need further imaging evaluation. If these
      results can be replicated in an independent and larger population, the practical
      definition of a benign cyst on imaging may be able to be expanded.

PMID- 29174192
TI  - Implementation of an antimicrobial stewardship program for patients with febrile
      neutropenia.
AB  - BACKGROUND: We aimed to describe the effectiveness of our standardized protocol
      for febrile neutropenia (FN), which was targeted to minimize unintended outcomes
      and reduce antimicrobial consumption. METHODS: The study was performed in a
      private hospital with 300 beds. We included all adult hematologic and oncologic
      cancer inpatients admitted between January 1, 2015-December 31, 2015, and January
      1, 2016-May 31, 2017. The outcomes of the study were fatality, infections, and
      adherence to the antimicrobial stewardship program (ASP). RESULTS: We included
      152 FN attacks of 95 adult inpatients from hematology and oncology wards; of
      these, 43% were women, and the median age was 57 years. The case fatality rate
      was 30% in the pre-ASP period and decreased to 11% in the post-ASP period (P =
      .024). The appropriate adding or changing (P = .006) and appropriate continuation
      or de-escalation or discontinuation of antimicrobials improved (P < .001). In the
      post-ASP period, Staphylococcus spp infections (from 22% to 8%, P = .02) and gram
      negative infections decreased (from 43% to 20%, P = .003). In the multivariate
      analysis, appropriate continuation or de-escalation or discontinuation was
      increased in the post-ASP period (odds ratio [OR], 4.3; 95% confidence interval
      [CI], 1.82-10.41; P = .001), and gram-positive infections were decreased (OR,
      0.32; 95% CI, 0.11-0.95, P = .041). Vancomycin and fluoroquinolone use decreased
      significantly. CONCLUSIONS: After implementation of the ASP, the case fatality
      rate among the patients with FN decreased. Appropriate antimicrobial use
      increased and overall antimicrobial consumption was reduced. Bacterial infections
      and Candida infections decreased.

PMID- 29174193
TI  - Environmental and body contamination from cleaning vomitus in a health care
      setting: A simulation study.
AB  - BACKGROUND: Environmental service workers may be exposed to pathogens during the
      cleaning of pathogen-containing bodily fluids. METHODS: Participants with
      experience cleaning hospital environments were asked to clean simulated,
      fluorescein-containing vomitus using normal practices in a simulated patient
      room. Fluorescein was visualized in the environment and on participants under
      black lights. Fluorescein was quantitatively measured on the floor, in the air,
      and on gloves and shoe covers. RESULTS: In all 21 trials involving 7
      participants, fluorescein was found on the floor after cleaning and on
      participants' gloves. Lower levels of floor contamination were associated with
      the use of towels to remove bulk fluid (rho = -0.56, P = .01). Glove
      contamination was not associated with the number or frequency of contacts with
      environmental surfaces, suggesting contamination occurs with specific events,
      such as picking up contaminated towels. Fluorescein contamination on shoe covers
      was measured in 19 trials. Fluorescein was not observed on participants' facial
      personal protective equipment, if worn, or faces. Contamination on other body
      parts, primarily the legs, was observed in 8 trials. Fluorescein was infrequently
      quantified in the air. CONCLUSIONS: Using towels to remove bulk fluid prior to
      mopping is part of the recommended cleaning protocol and should be used to
      minimize residual contamination. Contamination on shoes and the floor may serve
      as reservoirs for pathogens.

PMID- 29174194
TI  - Nerve growth factor is elevated in the CSF of patients with multiple sclerosis
      and central neuropathic pain.
AB  - Central neuropathic pain (CNP) is common and disabling among patients with
      multiple sclerosis (MS). The pathological mechanisms underlying CNP in MS are not
      well understood. We explored whether NGF is implicated in the pathogenesis of CNP
      in MS. We measured NGF concentration in the CSF of 73 patients affected by MS, 15
      with and 58 without CNP and 14 controls. We found increased levels of NGF in the
      CSF of patients with CNP compared to patients without and to controls. This
      finding supports the hypothesis that NGF plays a role in MS related CNP.

PMID- 29174195
TI  - Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of
      white matter-rich regions without altering flow in brain-irrigating arteries:
      Relationship to blood-brain barrier breakdown?
AB  - To better understand brain dysfunction during sepsis, cerebral arterial blood
      flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with
      Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance
      Imaging in rats after intraperitoneal administration of bacterial
      lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion
      of the corpus callosum region and diffusion parallel to its fibers were higher
      after lipopolysaccharide administration as compared to saline injection. In
      parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity
      in white matter. These findings indicate that systemic inflammation can result in
      increased perfusion, blood-brain barrier breakdown and altered water diffusion in
      white matter.

PMID- 29174196
TI  - Associations between intra-individual variability and Montreal Cognitive
      Assessment (MoCA) in cognitive ageing and prodromal dementia: A domain-specific
      perspective.

PMID- 29174197
TI  - Comparison of cardiac measurements by multi-detector computed tomography
      angiography and transthoracic echocardiography in English bulldogs.
AB  - INTRODUCTION: Transthoracic echocardiography (TTE) is the primary tool for the
      assessment of cardiac structure and function in dogs but is challenging in
      English bulldogs due to dorsoventral compression of the thorax, obesity, and
      narrow intercostal spaces. Multi-detector computed tomography angiography (CTA)
      may overcome the conformational obstacles of cardiac imaging in this breed.
      ANIMALS: Eleven client-owned English bulldogs. MATERIALS AND METHODS: Prospective
      clinical trial with paired analysis of TTE and CTA studies. RESULTS: Eight of the
      25 linear cardiac dimensional measurements were significantly different between
      TTE and CTA (p<0.033). Intraobserver agreement was strong with average
      coefficients of variation (CV) of 5.34% for TTE and 2.50% for CTA. Interobserver
      agreement CV averaged 6.5% for TTE and 8.75% CTA. Ejection fraction, stroke
      volume, and end-systolic volume were significantly different between modalities
      (all p<0.002). No significant difference was present between end-diastolic volume
      for TTE compared with CTA. DISCUSSION: High-quality cardiac angiographic studies
      were accomplished using CTA without the use of general anesthesia in English
      bulldogs. Multi-detector computed tomography angiography and TTE are not
      interchangeable modalities in the clinical setting. CONCLUSION: Multi-detector-CT
      ECG-gated cardiac angiography is possible in sedated, non-intubated English
      bulldogs. Differences were found between some cardiac dimensions as measured by
      TTE in the awake dog and compared with sedated CTA, indicating the two
      methodologies are not equivalent. Sedated, non-intubated CTA yielded high-quality
      imaging with strong intraobserver and interobserver measurement repeatability in
      English bulldogs.

PMID- 29174198
TI  - Management of benign papilloma without atypia diagnosed at ultrasound-guided core
      needle biopsy: Scoring system for predicting malignancy.
AB  - BACKGROUND: The management of benign intraductal papilloma diagnosed on core
      needle biopsy (CNB) remains unclear. This study was designed to evaluate factors
      predicting malignancy in patients diagnosed with benign papilloma without atypia
      at ultrasound-guided CNB and to develop a scoring system predicting malignancy
      based on clinical, radiological and pathological factors on further excisional
      biopsy. METHODS: The study enrolled patients diagnosed with benign papillomas
      (including benign and atypical papillary lesions) at CNB. Multivariate analysis
      was used to identify relevant clinical, radiological and pathological factors
      that may predict malignancy. RESULTS: A total of 520 CNBs were diagnosed with
      benign or atypical papilloma. Of these, 452 were benign papilloma without atypia.
      Of the 250 lesions subsequently excised surgically from 234 women, 17 (6.8%) were
      diagnosed with malignancy. Multivariate analysis revealed that bloody nipple
      discharge, size on imaging >=15 mm, BI-RADS>=4b, peripheral location and
      palpability were independent predictors of malignancy. A scoring system was
      developed based on logistic regression models and beta coefficients for each
      variable. The area under the ROC curve was 0.947 (95% CI: 0.913-0.981, p < 0.001)
      and a negative predictive value was 100%. In a validation set of 62 patients, an
      area under the ROC curve was 0.926 (95% CI: 0.857-0.995, p < 0.001). CONCLUSIONS:
      A scoring system predicting malignancy in patients diagnosed by CNB with benign
      papilloma without atypia was developed. This system was able to identify a subset
      of patients with lesions likely to be benign, indicating that imaging follow-up
      rather than surgical excision may be appropriate.

PMID- 29174199
TI  - Erratum to "Impact of Oncotype DX Breast Recurrence Score testing on adjuvant
      chemotherapy use in early breast cancer: Real world experience in Greater
      Manchester, UK" [Eur J Surg Oncol 43 (5) (2017) 931-937].

PMID- 29174200
TI  - Group 2: Adrenal insufficiency: screening methods and confirmation of diagnosis.
AB  - A diagnosis of adrenal insufficiency should be suspected in the presence of a
      number of non-specific symptoms (fatigue, anorexia, weight loss, hypotension,
      hyponatremia and hyperkalemia amongst adrenal causes of insufficiency). The
      diagnosis should be considered in case of pituitary disease or a state of shock.
      Treatment should be commenced immediately without waiting for confirmation from
      biochemical tests, which rely on cortisol level at 8am (expected to be low) and
      on ACTH level (expected to be high in the case of primary adrenal insufficiency).
      If these tests are inconclusive, a Synacthen test should be carried out. The
      threshold limits are provided as a guide. Low plasma cortisol and normal to low
      plasma ACTH indicates a pituitary origin for the deficiency. In this situation,
      the Synacthen test can give a false normal result, and if this adrenal
      insufficiency is strongly suspected, an insulin hypoglycemia test or metyrapone
      (Metopirone(r)) test should be carried out. In children younger than 2yr,
      hypoglycemia, dehydration and convulsions are frequently observed and in young
      girls, virilization is suspect of congenital adrenal hyperplasia . The circadian
      rhythm of cortisol is not present until after 4months of age and the Synacthen
      test is the only one that is feasible. In children older than 2yrs, the signs and
      diagnostic methods are the same as in the adult. Cessation of corticosteroid
      treatment is a frequent circumstance however there is little published data and
      no evidence for definitive guidelines. After ceasing a short period of
      corticosteroid treatment, patient education is all that is required. After longer
      treatment, consensus leaves the choice up to the physician, between educating the
      patient and prescribing hydrocortisone in case of stress, or prescribing low
      daily dose hydrocortisone and evaluating the ACTH axis over time until normal
      function is recovered.

PMID- 29174201
TI  - Group 5: Acute adrenal insufficiency in adults and pediatric patients.

PMID- 29174202
TI  - Graduate entry students' early perceptions of their future nursing careers.
AB  - Graduate entry nursing programs designed for individuals with prior degrees in
      other disciplines are becoming increasingly popular internationally. They provide
      entry into nursing for people with unique skill-sets. Yet, little is known about
      why these individuals choose career change into nursing and what they expect from
      their new careers. This component of a larger study sought to explore graduate
      entry nursing students' short and longer term career intentions on commencement
      of their courses. A cross-sectional survey was used. Descriptive frequencies were
      used to analyse demographic data, while summative content analysis was used with
      the open-ended questions. Participants were drawn from eight cohorts of
      commencing students from enrolled in one graduate entry masters program in
      Australia between 2009 and 2015. Content analysis identified three main
      categories: professional role, work location, and work context. Longer term
      responses were categorised under four categories: professional role, work
      location, work context and personal and professional goals. Many students had
      clear directions about their future nursing careers. On graduation, many
      envisioned working in advanced roles or in clinical specialty areas, primarily in
      hospital settings. However, in the longer term, there was diversity among with
      many envisaging work outside traditional hospital settings, and some in other
      health disciplines.

PMID- 29174203
TI  - Phase I/II Trial of Combined Pegylated Liposomal Doxorubicin and Cyclophosphamide
      in Metastatic Breast Cancer.
AB  - INTRODUCTION: Doxorubicin in combination with cyclophosphamide is active in
      breast cancer; however, its use in metastatic cancer is limited owing to
      cardiotoxicity. Pegylated liposomal doxorubicin (PLD) was formulated to decrease
      the toxicity of conventional doxorubicin. We evaluated the safety and efficacy of
      PLD with metronomic oral cyclophosphamide. PATIENTS AND METHODS: We conducted a
      single-arm open-label phase I/II study of PLD and oral cyclophosphamide in
      patients with metastatic breast cancer. In phase I, 3 escalating doses of PLD
      were planned (30, 35, and 40 mg/m2) with cyclophosphamide (60 mg/m2 orally daily)
      to determine the maximum tolerated dose (MTD). In phase II, the MTD of PLD in
      combination of oral cyclophosphamide was used to assess the primary endpoint of
      overall clinical response rate and secondary endpoints of progression-free
      survival, overall survival, and adverse events. RESULTS: Thirty patients were
      enrolled in the study (n = 6 in phase I and n = 24 in phase II). The MTD of PLD
      from phase I was 30 mg/m2. The median progression-free and overall survival for
      the entire cohort were 6.4 months (95% confidence interval, 3.9 months to N/A)
      and 18.7 months (95% confidence interval, 15.1-31.5 months), respectively. A
      total of 21 (75%) patients had clinical benefit, including 6 (21%) patients with
      partial response and 15 (54%) patients with stable disease. The majority of
      toxicities were uncomplicated myelosuppression, and no infection or febrile
      neutropenia were noted in any patient. CONCLUSION: PLD in combination with daily
      oral cyclophosphamide is an active and tolerable regimen in metastatic breast
      cancer.

PMID- 29174204
TI  - Leveraging Mega-trends in Medicine Today to Enhance Patient Care in Radiology
      Tomorrow.

PMID- 29174205
TI  - The Current State of Radiology Call Assistant Triage Programs Among US Radiology
      Residency Programs.
AB  - RATIONALE AND OBJECTIVES: Given increasing volume and workflow interruptions in
      radiology, we sought to identify and characterize radiology call assistant triage
      (RCAT) programs among US radiology residency programs. MATERIALS AND METHODS: A
      survey was created using Qualtrics survey software and emailed to all members of
      the Association of Program Directors in Radiology listserv. A total of 296 active
      members belong to this listserv, including program directors and assistant
      program directors. The survey included questions about the existence and
      specifics of a call triage assistant program. RESULTS: Data were obtained from 88
      active members of the Association of Program Directors in Radiology (30% response
      rate). Of those, 20 programs (23%) have an RCAT program. Triage assistant
      staffing includes nonmedical or clerical staff (60%), medical students (30%),
      first-year radiology residents (5%), and technologists (5%). All respondents with
      RCAT programs report satisfaction with their program and plan to continue. A
      significant majority (75%) have no plans to change, whereas the remaining 25% are
      considering program expansion and pay increases. Among residency programs without
      RCAT programs, none reported termination of their triage program. The most common
      reasons for not having triage assistants include cost, lack of awareness,
      differing opinions on utility, and the presence of 24/7 attending coverage.
      CONCLUSION: Twenty US radiology residency programs report having an RCAT program.
      All report satisfaction with their program despite different staffing models.
      RCAT programs may represent an effective measure in limiting interruptions and
      potentially decreasing interpretative errors made by residents on call.

PMID- 29174206
TI  - Selecting Cases for Resident Interpretation to Enhance the Teaching Experience.

PMID- 29174207
TI  - Detection of the Tram Track Lesion in the Ankle Joint: Comparing 3.0-Tesla
      Magnetic Resonance Imaging and Arthroscopy.
AB  - PURPOSE: To show the effectiveness of magnetic resonance imaging (MRI) for the
      detection of tram track lesions in the ankle compared with ankle arthroscopy.
      METHODS: We retrospectively assessed all patients who underwent arthroscopic
      ankle surgery between January 2013 and July 2015. Patients with anterior
      impingement spurs were included, but those with an osteochondral lesion or
      arthritis were excluded. Anterior ankle bony spurs on preoperative weight-bearing
      radiographs were scored using an impingement classification system. The 3.0-tesla
      MRIs were reviewed for tram track lesions (defined as focal high signal intensity
      along the talar dome cartilage surface on coronal views) and compared with
      arthroscopic findings. The cartilage defect grade at arthroscopy was stratified
      according to the International Cartilage Repair Society (ICRS) grading system.
      RESULTS: Overall, 175 ankles in 170 patients were evaluated. Tram track lesions
      were identified on MRI in 14 ankles (8.0%) and at arthroscopy in 16 ankles
      (9.1%). The overall sensitivity of MRI for the detection of tram track lesions
      was 87.5% and the specificity was 100%. On plain weight-bearing radiographs, of
      the 16 patients with confirmed tram track lesions on arthroscopy, 4 patients had
      grade 1, 2 had grade 2, and 10 had grade 3 impingement spurs. Under the ICRS
      grading system, 4 patients had grade II, 4 had grade III, and 8 had grade IV
      cartilage defects at arthroscopy. On MRI, 2 patients had grade II (50% of
      arthroscopy), 4 had grade III (100% of arthroscopy), and 8 had grade IV defects
      (100% of arthroscopy). The impingement spur grade showed no significant
      correlation with the arthroscopic ICRS grade of the tram track lesion (P = .609).
      CONCLUSION: Tram track lesions can be confidently detected on MRI with high
      sensitivity and specificity. The impingement spur grade did not correlate with
      the severity of cartilage injury of the talar dome. LEVEL OF EVIDENCE: Level III,
      diagnostic evaluation study.

PMID- 29174208
TI  - Does Azathioprine induce endoscopic and histologic healing in pediatric
      inflammatory bowel disease? A prospective, observational study.
AB  - BACKGROUND: The new concept of disease remission for pediatric inflammatory bowel
      diseases (IBD) implies the achievement of mucosal healing. AIMS: We aimed to
      evaluate endoscopic and histologic healing in children with Ulcerative Colitis
      (UC) and Crohn's disease (CD) in clinical remission after 52 weeks of
      Azathioprine. METHODS: From December 2012 to July 2015 we prospectively enrolled
      IBD children starting Azathioprine. Enrolled patients in clinical remission
      underwent colonoscopy after 52 weeks. Macroscopic assessment was described with
      Mayo score and the simplified endoscopic score for UC and CD, respectively. For
      microscopic assessment, an average histology score was used. Data on inflammatory
      markers and fecal calprotectin were also collected. RESULTS: Fourty-seven
      patients were included in the analysis. Endoscopic healing was detected in 20/26
      (76.9%) UC children and 10/21 (47.6%) CD patients. Median Mayo score and
      simplified endoscopic score were significantly decreased at week 52 (p<0.001;
      p=0.005). Median average histology score was not significantly different at week
      52 in both diseases. Fecal calprotectin was directly correlated with simplified
      endoscopic score (T0: r=0.4, p=0.05; T52: r=0.5, p=0.01), but not with Mayo
      score. No correlation was found between endoscopic and histologic scores.
      CONCLUSIONS: IBD children under Azathioprine reach endoscopic healing, but not
      histological remission.

PMID- 29174209
TI  - Intranasal fentanyl for acute severe pain episodes control in a dog.

PMID- 29174210
TI  - Ultrasound guided spinal catheter insertion in piglet: preliminary results.
AB  - OBJECTIVE: To describe the ultrasound (US) evaluation of the cervical, thoracic
      and lumbar spinal tracts in piglets and to evaluate the feasibility of the
      ultrasound guided spinal catheter placement in newborn and paediatric piglets.
      STUDY DESIGN: Prospective experimental study. ANIMALS: A total of two piglet
      cadavers (age, 7 and 14 days) and eight commercial crossbreed piglets divided
      into four groups according to age: 7 (P7), 14 (P14), 21 (P21) and 28 (P28) days.
      METHODS: In the first part of the study an ultrasound examination of the spinal
      tract was performed in piglet cadavers applying the transverse and the
      longitudinal approaches in sternal and lateral recumbencies. In the second phase,
      the piglets were anaesthetized with sevoflurane. A US examination with a 10 MHz
      linear probe was performed and a spinal catheter was introduced between the
      spinous processes of L2 and L3 lumbar vertebrae using an in-plane technique and
      its advancement was monitored with the probe. At the end of procedure, the
      catheter was removed. The piglets recovered from anaesthesia and were monitored
      for one week. RESULTS: In phase I the authors identified the paramedian
      longitudinal approach as the most feasible for spinal structure evaluation in
      piglets. In phase II, the paramedian longitudinal views enabled a good
      visualization of the spinal cord and of the catheter advancement up to the
      cisterna magna in groups P7 and P14. In groups P21 and P28 it was not possible to
      visualize the neuroaxial structures and the spinal catheter using the same
      approach. No clinical alterations were recorded during the procedure or the
      following days. CONCLUSIONS AND CLINICAL RELEVANCE: US-guided spinal catheter
      placement appeared a feasible technique in piglets younger than 14 days but it is
      not useful in older piglets.

PMID- 29174211
TI  - Retrospective study of intra-anesthetic predictors of prolonged hospitalization,
      increased cost of care and mortality for canine patients at a veterinary teaching
      hospital.
AB  - OBJECTIVE: To determine the impact of intraoperative anesthetic variables on the
      length of hospitalization, cost of care and mortality in dogs. STUDY DESIGN:
      Retrospective, observational study. ANIMALS: A total of 235 dogs undergoing
      general anesthesia. METHODS: Medical records of dogs undergoing general
      anesthesia between 2007 and 2014 at the University of Georgia Veterinary Teaching
      Hospital were reviewed. Data collected included demographic data, American
      Society of Anesthesiologists (ASA) physical status, type and duration of
      anesthesia, hemodynamic variables, temperature, ventilation, fluid therapy and
      adjunctive drugs administered. Outcome variables were length of hospitalization
      in the intensive care unit (ICU), hospital charges and survival to discharge.
      RESULTS: The only factor significantly associated with duration of ICU care was
      higher ASA status (p<0.0001). Factors associated with increased cost of
      hospitalization were ICU duration (p<0.0001), anesthesia duration (p<0.0001),
      hemorrhage amount (p<0.0001), colloid use (p=0.0081), increased age (p=0.0253),
      increased weight (p = 0.0293) and presence of hypertension (p=0.0179). Overall
      mortality rate was 5.1%. The only factors negatively associated with survival
      were the administration of colloids (p<0.0008) and ASA status (p=0.0314).
      CONCLUSIONS AND CLINICAL RELEVANCE: Several intrinsic patient factors and
      intraoperative hemodynamic variables were significantly associated with
      postoperative morbidity and mortality in dogs. These factors might have
      prognostic value in conjunction with preoperative risk assessment, and patient
      outcome may be improved by stricter intraoperative control of these variables.

PMID- 29174212
TI  - Women's Behaviors Toward Mammogram and Pap Test: Opportunities to Increase
      Cervical Cancer Screening Participation Rates among Older Women.
AB  - OBJECTIVES: Screening rates for cervical cancer remain moderate among women over
      50 years of age. Because cervical and breast screening interventions can be
      linked, evaluating screening factors relating to both is important. This study
      evaluates factors associated with breast and cervical screening participation in
      women aged 52 to 69. METHODS: A cross-sectional study was used to describe
      characteristics associated with screening behaviors of 1,173,456 eligible women
      in Ontario, Canada. Overdue for screening was defined as more than 2.5 years from
      last mammogram or more than 3.5 years from last Pap test. Factors that might
      influence uptake of mammogram or Pap test were included as covariates in a
      multivariable multinomial logistic regression model. RESULTS: Overall, 52.4% of
      eligible women were up-to-date for both, 21.3% were overdue for both, 14.4% were
      overdue for Pap test but were up-to-date with mammogram, and 11.9% were overdue
      for mammogram but were up-to-date with Pap test. There was an opposite effect of
      age on likelihood of being overdue for Pap test only versus mammogram only. Women
      aged 67 to 69 compared with those 52 to 54 were more likely to be overdue for Pap
      test only (adjusted odds ratio, 2.3; 95% confidence interval, 2.3-2.4) and less
      likely to be overdue for mammogram only (adjusted odds ratio, 0.5; 95% confidence
      interval, 0.5-0.6). A greater proportion of women rostered to a female physician
      versus a male physician were up-to-date for both (63.7% vs. 51.5%). CONCLUSIONS:
      Comparing screening patterns may provide physician- and patient-directed
      strategies to increase cervical screening participation by recruiting women who
      are overdue for Pap test but undergoing breast cancer screening.

PMID- 29174213
TI  - Treatment with levothyroxin in subclinical hypothyroidism is associated with
      increased mortality in the elderly.
AB  - INTRODUCTION: It is uncertain whether subclinical hypothyroidism should be
      treated with levothyroxine, particularly in the elderly. This study evaluated the
      association between levothyroxine treatment and mortality in individuals 65years
      or older with subclinical hypothyroidism and TSH values <10mIU/L. METHODS: A case
      control study in which patients 65years or older with TSH levels of 4.2-10mIU/L
      who died in the years 2012-2016 ('cases') were compared with matched individuals
      who did not die during this period ('controls'). Matching was based on gender,
      age, Charlson comorbidity index, date of TSH testing, duration of follow-up and
      TSH quartile. All cases of known thyroid disease or cases in which anti-thyroid
      medications or glucocorticoids were dispensed in the year preceding the TSH
      evaluation were excluded. Use of levothyroxine was compared between groups.
      RESULTS: During the follow-up period, 419 individuals died and these were matched
      with 1558 individuals who did not. Factors found to be associated with mortality
      were age, senile dementia, congestive heart failure, chronic renal failure and a
      history of cerebrovascular disease. On multivariate analysis, treatment with
      levothyroxine was associated with significantly increased mortality (HR=1.19 CI
      1.03-1.38). Femoral fractures and atrial fibrillation following initiation of
      levothyroxine therapy were not more prevalent in individuals who died during the
      follow-up period. CONCLUSIONS: Treatment with levothyroxine is associated with
      significantly increased mortality in individuals 65years or older with
      subclinical hypothyroidism and TSH<10.

PMID- 29174214
TI  - Impact of Left Atrial Appendage Exclusion on Cardiovascular Outcomes in Patients
      with Atrial Fibrillation Undergoing Coronary Artery Bypass Grafting (from the
      National Inpatient Sample Database).

PMID- 29174215
TI  - Choosing Dipeptidyl Peptidase-4 Inhibitors, Sodium-glucose Cotransporter-2
      Inhibitors, or Both, as Add-ons to Metformin: Patient Baseline Characteristics
      Are Crucial.
AB  - PURPOSE: Type 2 diabetes remains a poorly managed disease, with only about half
      of individuals with type 2 diabetes meeting guideline-recommended glycosylated
      hemoglobin (HbA1C) targets. A major proportion of those who have not met HbA1C
      goals have an HbA1C <8.0% to 8.5%. In practice, it is quite common to have to
      decide between dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose
      cotransporter-2 inhibitors (SGLT2i) as add-ons to metformin to help these
      individuals meet their HbA1C goals. This commentary reviews and provides guidance
      on how baseline factors can assist in the decision between the 2 classes or using
      both as add-ons to metformin. METHODS: The important clinical studies comparing
      the glycemic efficacy of DPP-4i versus SGLT2i or their combination as add-ons to
      metformin with a focus on the influence of baseline HbA1C on glycemic efficacy
      will be discussed and interpreted. The impact of estimated glomerular filtration
      rate and age on the glycemic efficacy of DPP-4i and SGLT2i will also be put into
      perspective. FINDINGS: At HbA1C <8.0% to 8.5%, HbA1C lowering is slightly greater
      with DPP-4i than with SGLT2i as an add-on to metformin; SGLT2i are associated
      with larger HbA1C improvements than DPP-4i at higher HbA1C levels. In cases of
      HbA1C >=8.0%, dual DPP-4i-SGLT2i add-on therapy to metformin should be considered
      to help more patients achieve glycemic targets. The glycemic efficacy of SGLT2i,
      but not DPP-4i, declines with progressive renal insufficiency. In older adults,
      DPP-4i maintain their tolerability and efficacy, while SGLT2i may become less
      efficacious due to reduced renal function, and may be associated with higher
      rates of volume-related adverse effects. IMPLICATIONS: Although both DPP-4i and
      SGLT2i are effective add-on antihyperglycemic therapies to metformin monotherapy,
      baseline characteristics, such as HbA1C, renal function, and age, should be
      considered when choosing between the 2 classes to allow for optimal and timely
      diabetes management.

PMID- 29174216
TI  - Pharmacokinetics of a New Amphetamine Extended-release Oral Liquid Suspension
      Under Fasted and Fed Conditions in Healthy Adults: A Randomized, Open-label,
      Single-dose, 3-treatment Study.
AB  - PURPOSE: A new amphetamine extended-release liquid formulation (AMP XR-OS),
      intended for the treatment of attention-deficit/hyperactivity disorder, has been
      developed. This study was performed to determine if administration with food
      affected the rate of absorption or bioavailability of AMP XR-OS. The formulation
      was also compared with an equivalent dose of an extended-release mixed
      amphetamine salts reference product (30 mg) under fed conditions. METHODS: Thirty
      adult volunteers participated in this single-dose, open-label, randomized, 3
      period, 3-treatment crossover study. Each participant received a single 15-mL
      dose of AMP XR-OS (equivalent to 30 mg of the reference drug) under fasted
      conditions, a single 15-mL dose of AMP XR-OS under fed conditions, and a single
      dose of the reference drug under fed conditions. A 7-day washout separated the 3
      treatment periods. Blood samples were collected at predetermined time points and
      analyzed for d- and l-amphetamine. Pharmacokinetic parameters reported are AUC0
      5, AUC0-last, AUC5-last, and AUC0-infinity; Cmax; elimination t1/2; and Tmax. The
      geometric mean ratios and 90% CIs of Cmax, AUC0-last, and AUC0-infinitywere
      determined for the comparison of AMP XR-OS fed and fasted, and Cmax, AUC0-5, AUC5
      last, and AUC0-infinity were calculated for AMP XR-OS compared with the reference
      drug under fed conditions. Safety was also assessed. FINDINGS: Twenty-nine
      subjects completed the study. Subjects were mostly male, white, and of
      Hispanic/Latino ethnicity with a mean age of 35.83 years and a mean BMI of
      25.36kg/m2. The 90% CIs of Cmax, AUC0-last, and AUC0-infinity for AMP XR-OS
      fasted versus fed were within the accepted 80% to 125% range, indicating lack of
      a food effect. In the comparison of AMP XR-OS fed versus the reference product,
      Cmax, AUC5-last, and AUC0-infinity were within the range to establish
      bioequivalence; however, AUC0-5 was significantly higher for AMP XR-OS compared
      with that of the reference drug. This difference between products was likely due
      to the known delay of Tmax and decreased exposure when the extended-release mixed
      amphetamine salts reference product is administered with food. A total of 36 mild
      or moderate adverse events were reported; 1 subject withdrew due to an adverse
      event, and no deaths occurred. These adverse events were consistent with the
      known pharmacodynamic effects of amphetamine. IMPLICATIONS: The absence of a food
      effect may allow for AMP XR-OS to be administered with or without a meal.

PMID- 29174217
TI  - Highlights of the Twelfth Annual Scientific Meeting of the Society of
      Cardiovascular Computed Tomography.
AB  - The 12th Annual Scientific Meeting of the SCCT, held from July 6 to July 9 in
      Washington, DC, was one of the largest to date with 724 attendants from 34
      countries, 130 invited talks, 4 "Read with the Experts" sessions, 42 oral
      abstracts presented, 20 rapid fire posters and 164 poster presentations with the
      abstracts of all of these published in the JCCT. This article summarises the many
      themes and topics of presentation and discussion in this meeting, and the many
      technical advances that are likely to impact future clinical practice and feature
      in future meetings.

PMID- 29174218
TI  - Individual differences in fear relapse.
AB  - Vulnerability to anxiety disorders might be due to enhanced acquisition of
      aversive associations, impaired inhibition of those associations (extinction),
      and/or vulnerability to the return of fear (relapse). Animal research
      investigating the processes underpinning fear learning, extinction, and relapse
      will be critical to further advancing our understanding of anxiety disorders and
      their treatment. Here we examined whether individual differences in the rate of
      extinction might be related to vulnerability to relapse. Relapse of fear was
      examined by testing animals for conditioned freezing using renewal,
      reinstatement, and spontaneous recovery procedures. Across all three experiments
      we found that when tested under "milder" relapse conditions (in a novel context,
      after a mild reinstatement procedure, or 8 days after extinction training) Slow
      Extinguishers exhibited relapse of fear whereas Fast Extinguishers did not.
      However, when tested under "stronger" relapse conditions (in the training
      context, after a strong reinstatement procedure, or 29 days after extinction
      training) both Fast and Slow Extinguishers exhibited comparable relapse of fear.
      These results show that Slow Extinguishers are more vulnerable to relapse than
      Fast Extinguishers. These findings have clinical implications for identifying
      those most at risk of relapse following treatment and highlight the importance of
      developing further strategies to reduce relapse.

PMID- 29174219
TI  - Familial diabetes of adulthood: A bin of ignorance that needs to be addressed.
AB  - AIMS: The aim of this article was to share with a wide readership some data and
      related reasoning about a multigenerational form of diabetes mellitus of
      adulthood. DATA SYNTHESIS: We have recently described a familial form of diabetes
      mellitus, which in the routine clinical setting of adult individuals is
      simplistically diagnosed as type 2 diabetes. Such misdiagnosis involves as much
      as 3% of adult unrelated diabetic patients with no evidence of autoimmune
      disease. More recent data, obtained by means of a next-generation sequencing,
      indicate that approximately 25% of such patients carry mutations in the genes
      involved in monogenic diabetes, thus leaving unraveled the molecular causes of
      the remaining 75% individuals. CONCLUSIONS: Our proposal is to define the latter
      patients as being affected by familial diabetes of adulthood (FDA), a clear
      admission of ignorance and a limbo where adult patients with multigenerational
      diabetes with no genetic definition of their hyperglycemia have to wait for
      better times.

PMID- 29174220
TI  - Outcomes of children supported with devices labeled as "temporary" or short term:
      A report from the Pediatric Interagency Registry for Mechanical Circulatory
      Support.
AB  - BACKGROUND: Historically, the "temporary" or short-term ventricular assist device
      (VAD) was used only as a quick bridge to recovery for children with an acute
      process. In the current era, the devices that were originally used for temporary
      support are now being used to support children for longer durations and for a
      variety of indications. In this study we aimed to describe the overall use,
      patients' characteristics and outcomes of "temporary" VAD use in children.
      METHODS: The Pediatric Interagency Registry for Mechanical Circulatory Support
      (PediMACS) is a National Institutes of Health-supported national registry for
      United States Food and Drug Administration-approved VADs in patients <19 years of
      age at the time of VAD implantation (either durable or temporary VAD). Patients
      undergoing placement of a device classified as a temporary VAD between September
      19, 2012 and June 30, 2016 were included. RESULTS: Temporary VADs were implanted
      in 63 patients at 20 centers, accounting for 19% of all pediatric VAD patients
      entered into PediMACS. The median age at implantation was 3.7 (range <1 day to
      18) years. The underlying diseases were: congenital heart disease in 26 (41%), 20
      of whom were classified as single ventricle; cardiomyopathy in 25 (40%); and
      myocarditis/rejection in 12 (19%). Patients were predominately Interagency
      Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1
      (51%), and 10 patients (16%) had previously been supported with extracorporeal
      membrane oxygenation. Median duration of support was 15 (range <1 day to 227)
      days, with 41 patients (65%) being on support for >=10 days. The most frequent
      adverse events were bleeding (29% of patients) and neurologic dysfunction (24% of
      patients). Overall, 71% (45) achieved a positive outcome (defined as bridge to
      recovery [30%], transplantation [17%], alive on device [2%] or transition to
      durable VAD [22%]). Eighty-eight percent (n = 22) of the cardiomyopathy patients
      and 60% (n = 12) of the single-ventricle patients achieved a favorable outcome.
      CONCLUSION: Devices historically classified as "temporary" pumps are being used
      not only as a short-term mechanical circulatory support strategy but also as a
      longer term support strategy. In this multi-institutional, high-acuity, complex
      patient cohort, the use of "temporary" VADs resulted in a positive outcome
      (bridge to transplant, recovery durable device or alive) in 71% of patients.

PMID- 29174221
TI  - Lung Toxicity in Non-Small-Cell Lung Cancer Patients Exposed to ALK Inhibitors:
      Report of a Peculiar Case and Systematic Review of the Literature.
AB  - Lung toxicity is a potential fatal effect involving non-small-cell lung cancer
      (NSCLC) patients exposed to tyrosine kinase inhibitors (TKIs). Moving from our
      experience regarding a patient who developed lung toxicity while receiving 2
      different anaplastic lymphoma kinase (ALK)-TKIs, we performed a systematic review
      to assess the epidemiologic magnitude and the clinical significance of such
      toxicity in NSCLC patients treated with ALK-TKIs. Studies were identified using
      MEDLINE and additional sources (European Society for Medical Oncology, American
      Society of Clinical Oncology, and World Conference on Lung Cancer abstracts) in
      agreement with Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      and Cochrane guidelines. Lung toxicity was reported in 105 of 4943 NSCLC patients
      (2.1%). Crizotinib was responsible for pulmonary adverse events (AEs) in 1.8% of
      exposed patients (49 of 2706). With the limit of a lower number of treated
      patients (n = 359), brigatinib resulted as the most frequently involved in lung
      toxicity (7%; n = 25). Pulmonary AEs during therapy with ceritinib, alectinib,
      and lorlatinib occurred in 1.1%, 2.6%, and 1.8% of the patients, respectively.
      Sixty-five percent of cases accounted for Grade 3 or 4 events, with a mortality
      rate of 9%. Radiological patterns of pneumonia were reported in 25 patients,
      whereas imaging evocative of interstitial lung disease in 37. Overall, 26 of 105
      patients (25%) permanently discontinued treatment because of lung toxicity. Lung
      toxicity is a rare albeit potentially severe side effect in NSCLC patients
      receiving ALK-TKIs, apparently more frequent with brigatinib. Its early
      recognition and treatment are crucial for the best outcome of this subgroup of
      patients, whose overall prognosis is being improved by the availability of
      several targeted agents.

PMID- 29174222
TI  - Inter- and intrarater reliability of two proprioception tests using clinical
      applicable measurement tools in subjects with and without knee osteoarthritis.
AB  - BACKGROUND: The therapeutic value of proprioceptive-based exercises in knee
      osteoarthritis (KOA) management warrants investigation of proprioceptive testing
      methods easily accessible in clinical practice. OBJECTIVE: To estimate inter- and
      intrarater reliability of the knee joint position sense (KJPS) test and knee
      force sense (KFS) test in subjects with and without KOA. DESIGN: Cross-sectional
      test-retest design. METHOD: Two blinded raters performed independently repeated
      measures of the KJPS and KFS test, using an analogue inclinometer and handheld
      dynamometer, respectively, in eight KOA patients (12 symptomatic knees) and 26
      healthy controls (52 asymptomatic knees). Intraclass correlation coefficients
      (ICCs; model 2,1), standard error of measurement (SEM) and minimal detectable
      change with 95% confidence bounds (MDC95) were calculated. RESULTS: For KJPS,
      results showed good to excellent test-retest agreement (ICCs 0.70-0.95 in KOA
      patients; ICCs 0.65-0.85 in healthy controls). A 2 degrees  measurement error
      (SEM 1 degrees ) was reported when measuring KJPS in multiple test positions and
      calculating mean repositioning error. Testing KOA patients pre and post therapy a
      repositioning error larger than 4 degrees  (MDC95) is needed to consider true
      change. Measuring KFS using handheld dynamometry showed poor to fair interrater
      and poor to excellent intrarater reliability in subjects with and without KOA.
      CONCLUSIONS: Measuring KJPS in multiple test positions using an analogue
      inclinometer and calculating mean repositioning error is reliable and can be used
      in clinical practice. We do not recommend the use of the KFS test to clinicians.
      Further research is required to establish diagnostic accuracy and validity of our
      KJPS test in larger knee pain populations.

PMID- 29174223
TI  - Novel Areas for Prevention and Control of Canine Leishmaniosis: (Trends in
      Parasitology 33, 718-730; 2017).

PMID- 29174224
TI  - Spotlight on CRISPR in Strongyloides Parasitic Nematodes.
AB  - Parasitic nematodes are biomedically and economically important, but many are
      genetically intractable which limits our understanding of their molecular and
      cellular biology. Gang et al. report CRISPR/Cas9 genome editing in parasites of
      the genus Strongyloides, generating both knock-outs and knock-ins, and
      demonstrated heritability of the modifications, a crucial advance in the field.

PMID- 29174225
TI  - Diagnostic Accuracy of Digital Breast Tomosynthesis in the Evaluation of Palpable
      Breast Abnormalities.
AB  - RATIONALE AND OBJECTIVES: The role of digital breast tomosynthesis (DBT) in
      evaluating palpable abnormalities has not been evaluated and its accuracy
      compared to 2D mammography is unknown. The purpose of this study was to evaluate
      combined 2D mammography, DBT, and ultrasound (US) at palpable sites. MATERIALS
      AND METHODS: Two breast imagers reviewed blinded consecutive cases with combined
      2D mammograms and DBT examinations performed for palpable complaints. By
      consensus, 2D and DBT findings were recorded and compared to US. Patient
      characteristics, demographics, subsequent workup, and outcome were recorded.
      RESULTS: A total of 229 sites in 188 patients were included, with 50 biopsies
      performed identifying 18 cancers. All 18 cancers were identified on 2D and US,
      whereas 17 cancers were identified on DBT. Cancer detection sensitivities for 2D,
      DBT, and US were 100.0%, 94.4%, and 100.0%. The negative predictive value, when
      combined with US, was 100% for both. The sensitivity and the specificity for both
      benign and malignant findings with 2D and DBT were 70.5% versus 75.4% (P = 0.07)
      and 95.3% versus 99.1% (P = 0.125). Palpable findings not identified by 2D and
      DBT were smaller than those identified (11.5 +/- 8.3 mm vs 23.9 +/- 12.8 mm, P <
      0.001). Patients with dense breasts were more likely to have mammographically
      occult findings than patients with nondense breasts (27.4% vs 8.3%). CONCLUSIONS:
      DBT did not improve cancer detection over 2D or US. Both mammographic modalities
      failed to identify sonographically confirmed findings primarily in dense breasts.
      The diagnostic use of DBT at palpable sites provided limited benefit over
      combined 2D and US. When utilizing DBT, US should be performed to adequately
      characterize palpable sites.

PMID- 29174226
TI  - Optical Coherence Tomography: A Novel Imaging Method for Post-lumpectomy Breast
      Margin Assessment-A Multi-reader Study.
AB  - RATIONALE AND OBJECTIVES: This study aimed to assess whether different breast
      cancer subspecialty physicians can be trained to distinguish non-suspicious from
      suspicious areas of post-lumpectomy specimen margin in patients with breast
      cancer using optical coherence tomography (OCT) images (a near-infrared based
      imaging technique) with final histology as the reference standard. MATERIALS AND
      METHODS: This institutional review board-exempt, Health Insurance Portability and
      Accountability Act-compliant study was performed on 63 surgically excised breast
      specimens from 35 female patients, creating a 90-case atlas containing both non
      suspicious and suspicious areas for cancer. OCT images of the specimens were
      performed, providing 6.5-15 um resolution with tissue visualization 1-2 mm
      subsurface. From the 90-case atlas, 40 cases were chosen for training and 40 were
      randomly selected for reader assessment. Three breast imaging radiologists, two
      pathologists, two breast surgeons, and one non-clinical reader were trained and
      assessed for ability to distinguish non-suspicious from suspicious findings
      blinded to clinical data and corresponding histology slides. Duration of training
      and assessment, sensitivity, specificity, positive predictive value, negative
      predictive value, and the area under the curve for each reader were calculated as
      well as averages by subspecialty. RESULTS: The average training time was 3.4
      hours (standard deviation, 1.2). The average assessment time was 1.9 hours
      (standard deviation, 0.7). The overall average reader sensitivity, specificity,
      and accuracy for detecting suspicious findings with histologic confirmation of
      cancer at the surgical margin for all eight readers were 80%, 87%, and 87%,
      respectively. Radiologists demonstrated the highest average among the
      disciplines, 85%, 93%, and 94%, followed by pathologists, 79%, 90%, and 84%, and
      surgeons, 76%, 84%, and 82% respectively. CONCLUSIONS: With relatively short
      training (3.4 hours), readers from different medical specialties were able to
      distinguish suspicious from non-suspicious OCT imaging findings in ex vivo breast
      tissue as confirmed by histology. These results support the potential of OCT as a
      real-time intraoperative tool for post-lumpectomy specimen margin assessment.

PMID- 29174227
TI  - Angiogenic and antiangiogenic factors in preeclampsia.
AB  - BACKGROUND: Pre-eclampsia is a multifactorial hypertensive disorder that is
      triggered by placental insufficiency and that accounts for up to 15% of maternal
      deaths. In normal pregnancies, this process depends on the balance between the
      expression of angiogenic factors and antiangiogenic factors, which are
      responsible for remodeling the spiral arteries, as well as for neoangiogenesis
      and fetal development. PURPOSE: The aim of this review is to discuss the main
      scientific findings regarding the role of angiogenic and antiangiogenic factors
      in the etiopathogenesis of preeclampsia. METHODS: An extensive research was
      conducted in the Pubmed database in search of scientific manuscripts discussing
      potential associations between angiogenic and antiangiogenic factors and
      preeclampsia. Ninety-one papers were included in this review. RESULTS: There is
      an increased expression of soluble fms-like tyrosine kinase receptor and soluble
      endoglin in pre-eclampsia, as well as reduced placental expression of vascular
      endothelial growth factor and placental growth factor. Systemic hypertension,
      proteinuria and kidney injury - such as enlargement and glomerular fibrin
      deposit, capillary occlusion due to edema, and hypertrophy of endocapillary cells
      - are some of these changes. The complex etiopathogenesis of preeclampsia
      instigates research of different biomarkers that allow for the early diagnosis of
      this entity, such as vascular endothelial growth factor, placental growth factor,
      soluble fms-like tyrosine kinase receptor, soluble endoglin, placental
      glycoprotein pregnancy-associated plasma protein-A and protein 13. CONCLUSION:
      Even though it is possible to establish an efficient and effective diagnostic
      tool, three key principles must be observed in the management of preeclampsia:
      prevention, early screening and treatment.

PMID- 29174228
TI  - Rare Concurrent Retroclival and Pan-Spinal Subdural Empyema: Review of Literature
      with an Uncommon Illustrative Case.
AB  - BACKGROUND: Subdural empyema can present as a spinal subdural empyema (SSE) or a
      cranial subdural empyema (CSE). Although they differ somewhat in epidemiology,
      etiology, pathophysiology, and symptomatology and occur separately, they rarely
      manifest together. The aim of this article is to review the literature concerning
      the clinical presentation, clinical course, and treatment options for managing
      concurrently occurring SSE and CSE. METHODS: The literature in the Medline
      database was reviewed with key words including but not limited to subdural
      empyema, retroclival empyema, and Streptococcus mitis. No similar reports were
      found in the database involving infection with this type of microorganism in this
      anatomical region. RESULTS: Only 3 cases with concurrent CSE and SSE were found
      in the literature caused by various etiologic agents. Two of the patients
      recovered with no neurologic deficit, whereas one fatality was reported. One new
      illustrative case caused by Streptococcus mitis is also presented. CONCLUSIONS:
      CSE and SSE are neurosurgical emergencies, often requiring prompt surgical
      evacuation. Although very rare, Streptococcus mitis can cause spinal subdural
      empyema or retroclival abscesses. Natural history of this disease is grave
      without treatment. Delays in diagnosis and treatment are directly related to
      mortality and severe morbidity in patients with intracranial and spinal subdural
      empyema. Prompt recognition and treatment are essential to preclude severe
      neurologic disabilities or in rare cases a fatal outcome. A treatment paradigm
      for cranio-spinal empyema is proposed.

PMID- 29174229
TI  - Repair of Cerebrospinal Fluid Leakage Using a Transfrontal, Radial Adipofascial
      Flap: An Individual Approach Supported by Three-Dimensional Printing for Surgical
      Planning.
AB  - BACKGROUND: Leakage of cerebrospinal fluid (CSF) because of large prolactinomas
      represents a complex issue. Because of limited anatomic space, multiple leakage
      sites, and scarce locally available tissue for repair, surgical possibilities are
      limited. We report an initial case of using a radial fasciocutaneous flap applied
      subfrontally to cover a large skull base defect, supported by preoperative three
      dimensional (3D) printing for surgical planning. CASE DESCRIPTION: A 29-year-old
      woman developed severe nuchal pain that was caused by destruction of large parts
      of her skull base by a prolactinoma. After occipitocervical fusion, medical
      treatment showed good tumor response but led to CSF leakage after 12 months. An
      endoscopic approach and ventriculoperitoneal shunt implantation failed to stop
      the leakage. A 3D model of the skull improved the understanding of the expanded
      osseous destruction and multiple CSF leakage sites and supported surgical
      planning. For an extensive coverage of the former clivus and sella region, an
      intracranially applied radial flap was planned. Dopamine-agonist medication was
      increased before the operation. Intraoperatively, the flap was brought into
      position subchiasmatically and wound around the pituitary stalk. CSF leakage was
      not observed on follow-up (10 weeks). Long-term follow-up will determine the
      effectiveness of this method.

PMID- 29174230
TI  - Utility of the Lateral Base Dural Tacking Method in Cord Tumor Surgery Performed
      Using Unilateral Hemilaminectomy: A Comparison of Dural Window Widths.
AB  - OBJECTIVE: Unilateral hemilaminectomy, which is used to remove spinal cord
      tumors, is simpler than laminoplastic laminotomy and affords certain
      biomechanical advantages. However, both incomplete tumor removal and inadvertent
      infliction of spinal cord damage attributable to the narrow surgical corridor
      remain of concern. When a spinal cord tumor is to be removed, it is important to
      ensure that the dural window along the surgical corridor is of adequate width.
      This study aimed to determine that the utility of lateral base dural tacking
      (LBT) method when cord tumor surgery is performed using a unilateral
      hemilaminectomy-a comparison of dural window widths with a traditional dural tack
      up and a suspending-out (DSO) method with the aid of digital image-analysis
      software. METHODS: Twenty-one consecutive patients who had intradural
      extramedullary spinal cord tumors removed using a unilateral hemilaminectomy were
      included in the study and analyzed retrospectively. We acquired DSO and LBT dural
      window images using surgical microscopes under identical conditions in
      consecutive order and then removed the tumors using the LBT method. We used
      digital image-analysis software to analyze the images quantitatively. The pixel
      numbers of LBT and DSO window were compared using a paired t test. RESULTS:
      Twenty-one tumorous lesions were successfully removed without any major problems
      using a unilateral hemilaminectomy through LBT windows. The mean pixel numbers of
      the LBT and DSO windows were 126,787 +/- 41,938 and 85,940 +/- 21,638. The LBT
      windows were 46% larger than the DSO windows (P < 0.001). CONCLUSIONS: We
      objectively proved that the utility of the LBT method for widening the surgical
      corridor created during hemilaminectomy.

PMID- 29174231
TI  - Angiographic Appearance of Pulsatile Blister Aneurysm.
AB  - A male with detected subarachnoid hemorrhage was admitted to our center. During
      the first angiography, a pulsatile blister aneurysm was revealed and the aneurysm
      was also noticeably enlarged during the surveillance angiography. The patient
      accepted balloon-assisted clipping successfully. Blister aneurysms are at a high
      risk of rupture, high risk of regrowth, and need for multimodal management.

PMID- 29174232
TI  - Endovascular Mechanical Thrombectomy in Large-Vessel Occlusion Ischemic Stroke
      Presenting with Low National Institutes of Health Stroke Scale: Systematic Review
      and Meta-Analysis.
AB  - INTRODUCTION: Mechanical thrombectomy has become the standard of care for
      management of most large vessel occlusion (LVO) strokes. When patients with LVO
      present with minor stroke symptomatology, no consensus on the role of mechanical
      thrombectomy exists. METHODS: A systematic review and meta-analysis were
      performed to identify studies that focused on mechanical thrombectomy, either as
      a standalone treatment or with intravenous tissue plasminogen activator (IV tPA),
      in patients with mild strokes with LVO, defined as a baseline National Institutes
      of Health Stroke Scale score <=5 at presentation. Data on methodology, quality
      criteria, and outcome measures were extracted, and outcomes were compared using
      odds ratio as a summary statistic. RESULTS: Five studies met the selection
      criteria and were included. When compared with medical therapy without IV tPA,
      mechanical thrombectomy and medical therapy with IV tPA were associated with
      improved 90-day modified Rankin Scale (mRS) score. Among medical patients who
      were not eligible for IV tPA, those who underwent mechanical thrombectomy were
      more likely to experience good 90-day mRS than those who were not. There was no
      significant difference in functional outcome between mechanical thrombectomy and
      medical therapy with IV tPA, and no treatment subgroup was associated with
      intracranial hemorrhage or death. CONCLUSIONS: In patients with mild strokes due
      to LVO, mechanical thrombectomy and medical therapy with IV tPA led to better 90
      day functional outcome. Mechanical thrombectomy plays an important role in the
      management of these patients, particularly in those not eligible for IV tPA.

PMID- 29174233
TI  - Effectiveness of Gamma Knife Radiosurgery in Improving Psychophysical Performance
      and Patient's Quality of Life in Idiopathic Trigeminal Neuralgia.
AB  - OBJECTIVE: To assess effectiveness of Gamma Knife Radiosurgery (GKRS) in
      improving quality of life (QoL) in patients with idiopathic trigeminal neuralgia
      (TN). METHODS: Between January 2001 and October 2013, 166 patients with medically
      resistant TN were treated at our institution with GKRS. Patients were divided
      into 2 groups: patients with typical TN (TTN) and patients with atypical TN
      (ATN). All patients underwent clinical evaluation using Marseille and Barrow
      Neurological Institute pain and numbness scales; in addition, they completed the
      Short-Form 36 Health Survey, Activities of Daily Living, and Excellent Good Fair
      Poor questionnaires and underwent psychological and neurologic examination.
      RESULTS: Mean follow-up time was 64.7 months. All Short-Form 36 domains were
      significantly improved in both groups after treatment, with an evident trend to
      reach the median values of healthy Italian population. Mean postoperative
      Activities of Daily Living score in the TTN group and ATN group were 5.8 and 5.4,
      respectively, and Karnofsky Performance Status increased to 94.2 and 86.4,
      respectively. Pain recurrence negatively affected patients' QoL and
      psychofunctional performance without reaching statistical significance. At the
      last follow-up, 73% of patients were clustered in the pain-relief group.
      CONCLUSIONS: GKRS significantly improves QoL and functional and psychosocial
      performance of patients with idiopathic trigeminal neuralgia. A trend was
      observed toward a more favorable outcome in patients with TTN, compared with
      patients with ATN, without reaching a statistically significant distinction.

PMID- 29174234
TI  - In Situ Side-to-Side Anastomosis: Surgical Technique and Complication Avoidance.
AB  - In situ side-to-side (STS) anastomosis is a unique technique used for
      intracranial artery-intracranial artery revascularization. Over a 7-year period,
      7 STS anastomoses were performed for anterior cerebral artery aneurysms in 6
      patients and a posteroinferior cerebellar artery aneurysm in 1 patient. We
      provide a step-by-step guide for suturing techniques from arteriotomy to vessel
      wall sutures based on clinical experiences, with detailed illustrations.
      Technical considerations in each stage are also discussed. The current technique
      provides a viable option for treatment of complex aneurysms.

PMID- 29174235
TI  - Hybrid Recanalization for Symptomatic Long-Segmental Occlusion Post Vertebral
      Artery Stenting.
AB  - BACKGROUND: A hybrid operation combining endovascular and open surgery procedures
      is supposed to achieve recanalization for post-stenting long-segmental occlusion
      of the vertebral artery (VA) ostium simultaneously. CASE DESCRIPTION: One patient
      with post-stenting long-segmental occlusion in VA ostium was reported. His
      symptoms could not be relieved by medical therapy. Recanalization combining
      endovascular and open surgery procedures simultaneously was performed. The hybrid
      recanalization was successful, and the patient demonstrated no symptoms attacked
      during the follow-up. CONCLUSIONS: Hybrid operation is a potential and feasible
      method to recanalize the long-segmental occlusion in the VA ostium post-stenting
      treatment.

PMID- 29174236
TI  - Paradoxical Distraction with Upright Position After Halo Fixation in 2 Patients
      with Atlanto-Occipital Dislocation.
AB  - BACKGROUND: Atlanto-occipital dislocation (AOD) is the most uncommon form of
      traumatic cervical spine injury. The majority of patients die before reaching
      higher-level care, and only a small percentage of patients with AOD survive the
      initial injury after receiving tertiary care. As such, there is a paucity of
      evidence-based management guidelines for treating this condition. Halo vest
      fixation has been a proposed method for interim stability while these patients
      undergo medical optimization for surgical intervention. There have been several
      reports of worsening AOD after halo placement. Reverse Trendelenburg position
      after halo fixation has been previously described to aid in the reduction of AOD,
      as well as concomitant atlantoaxial dislocation by gravitational downward force.
      CASE DESCRIPTION: In this series we present 2 cases of obese patients (body mass
      index >30) with AOD treated by halo fixation that had increased distraction after
      head of bed elevation. CONCLUSION: Our theorized mechanism for this phenomenon is
      due to the downward pull of subaxial forces secondary to a large body habitus.

PMID- 29174237
TI  - Midline Ligamentum Flavum Cyst of Lumbar Spine.
AB  - BACKGROUND: Ligamentum flavum cysts are thought to develop due to facet joint
      hypermobility; however, the etiology of these lesions is not completely
      elucidated. These cysts may lead to compressive pathologies of the spine
      requiring surgical intervention. CASE REPORT: We report the case of a 63-year-old
      male with chronic back pain and progressive neurogenic claudication for 6 months.
      He was found to have a ligamentum flavum cyst situated along the dorsal midline
      of the lumbar spinal canal contributing to spinal stenosis. The patient underwent
      a decompressive L4 laminectomy and en bloc excision of the ligamentum flavum cyst
      with complete resolution of his symptoms postoperatively. CONCLUSIONS: We suggest
      that chronic mechanical stress leads to degeneration of the ligamentum flavum and
      contributes directly to cyst formation.

PMID- 29174238
TI  - Association of Hospital Teaching Status with Neurosurgical Outcomes: An
      Instrumental Variable Analysis.
AB  - BACKGROUND: The interpretation of the results of prior studies on the association
      of hospital teaching status with surgical outcomes is limited by selection bias.
      We investigated whether undergoing surgical operations in teaching hospitals is
      associated with improved outcomes. METHODS: We performed a cohort study of all
      patients undergoing spine and cranial operations who were registered in the New
      York Statewide Planning and Research Cooperative System database from 2009 to
      2013. We examined the association of teaching status (defined as academic
      affiliation for the primary analysis) with inpatient case fatality, discharge to
      a facility, and length of stay (LOS). An instrumental variable analysis was used
      to control for unmeasured confounding and to simulate the effect of a randomized
      trial. RESULTS: During the study period, 186,483 patients underwent surgical
      operations that met the inclusion criteria. Instrumental variable analysis
      demonstrated that hospitalization in teaching hospitals was associated with
      higher rates of case fatality (adjusted difference, 25%; 95% confidence interval
      [CI], 4%-46%), discharge to a facility (adjusted difference, 5.7%; 95% CI, 4.5%
      7.0%), and longer LOS (adjusted difference, 31.4%; 95% CI, 16.0%-46.1%) in
      comparison with nonteaching hospitals. The same associations were present in
      propensity score adjusted mixed effects models. These persisted in prespecified
      subgroups stratified on particular operations and for different definitions of
      teaching hospitals. CONCLUSIONS: Using a comprehensive all-payer cohort of
      surgical patients in New York State, we identified an association of treatment in
      teaching hospitals with increased case fatality, rate of discharge to
      rehabilitation, and longer LOS. Further research into the factors contributing to
      superior outcomes in nonteaching institutions is warranted.

PMID- 29174239
TI  - Efficiency and Safety of Autologous Fat Grafts in Reconstructing Skull Base
      Defects After Resection of Skull Base Meningiomas.
AB  - BACKGROUND: Reconstruction of the skull base after resection of skull base
      meningiomas is of paramount importance. Here we describe a safe and effective
      method of skull base reconstruction using autologous free fat grafts. METHODS: In
      this retrospective analysis of patients operated for skull base meningioma from
      2007 to 2014. We analyzed the surgical technique, efficiency and safety as well
      as the graft-related complications. RESULTS: Autologous free fat grafts were used
      in 55 patients, including 39 patients with posterior fossa meningiomas related to
      the petrous bone and 16 patients with anterior fossa meningiomas related to the
      paranasal sinuses. Three patients experienced postoperative cerebrospinal fluid
      (CSF) leak and were managed with temporary continuous lumbar drainage. One
      patient developed pneumocephalus and required revision. The occurrence of CSF
      leak was related to aggressive resection with resulting large skull base defects,
      especially in anterior skull base meningiomas. There were no donor site-related
      complications. CONCLUSIONS: The use of autologous free fat grafts is an effective
      and safe technique for reconstructing skull base defects after microsurgical
      resection of skull base meningiomas.

PMID- 29174240
TI  - Predicting Resident Performance from Preresidency Factors: A Systematic Review
      and Applicability to Neurosurgical Training.
AB  - BACKGROUND: Neurosurgical educators strive to identify the best applicants, yet
      formal study of resident selection has proved difficult. We conducted a
      systematic review to answer the following question: What objective and subjective
      preresidency factors predict resident success? METHODS: PubMed, ProQuest, Embase,
      and the CINAHL databases were queried from 1952 to 2015 for literature reporting
      the impact of preresidency factors (PRFs) on outcomes of residency success (RS),
      among neurosurgery and all surgical subspecialties. Due to heterogeneity of
      specialties and outcomes, a qualitative summary and heat map of significant
      findings were constructed. RESULTS: From 1489 studies, 21 articles met inclusion
      criteria, which evaluated 1276 resident applicants across five surgical
      subspecialties. No neurosurgical studies met the inclusion criteria. Common
      objective PRFs included standardized testing (76%), medical school performance
      (48%), and Alpha Omega Alpha (43%). Common subjective PRFs included aggregate
      rank scores (57%), letters of recommendation (38%), research (33%), interviews
      (19%), and athletic or musical talent (19%). Outcomes of RS included faculty
      evaluations, in-training/board exams, chief resident status, and research
      productivity. Among objective factors, standardized test scores correlated well
      with in-training/board examinations but poorly correlated with faculty
      evaluations. Among subjective factors, aggregate rank scores, letters of
      recommendation, and athletic or musical talent demonstrated moderate correlation
      with faculty evaluations. CONCLUSION: Standardized testing most strongly
      correlated with future examination performance but correlated poorly with faculty
      evaluations. Moderate predictors of faculty evaluations were aggregate rank
      scores, letters of recommendation, and athletic or musical talent. The ability to
      predict success of neurosurgical residents using an evidence-based approach is
      limited, and few factors have correlated with future resident performance. Given
      the importance of recruitment to the greater field of neurosurgery, these data
      provide support for a national, prospective effort to improve the study of
      neurosurgery resident selection.

PMID- 29174241
TI  - A Novel Skin and Fascia Opening for Subfascial Inserting of Intrathecal Baclofen
      Pump.
AB  - OBJECTIVE: The aim of this article is to introduce a new skin and fascia opening
      for intrathecal baclofen pump implantation in the abdomen, with the purpose of
      reducing complications related to wound breakdown. METHODS: We introduce a novel
      way of cutaneous and fascial opening that leads two opposed "L shaped" incisions.
      RESULTS: This method entails numerous advantages. The first advantage is avoiding
      the direct alignment of overlapped sutures, which creates a locus minoris
      resistentiae that can weaken and break under the push of the pump. Another
      advantage consists of an increased obstruction against deep extension of
      infective processes from cutaneous origin. The wide opening of the subfascial
      pocket permits the implantation of any type of pump available, and it reduces
      complexities in reopening the pouch for pump replacement. It also permits the
      fastening of all anchoring systems usually present in pumps. Another advantage is
      the improved possibility of careful muscle cauterization thanks to the wide
      fascia opening, with reduced risk of postsurgical hematoma. Our results showed a
      reduction of wound complications with this method. CONCLUSIONS: This method could
      contribute to reducing the rate of wound complications and patient discomfort.

PMID- 29174242
TI  - Bioresorbable scaffold -fourth revolution or failed revolution: Is low scaffold
      strut thickness the wrong target?
AB  - Bioresorbable scaffold (BRS) technology has currently fallen into disrepute
      because of inordinately high risk of scaffold thrombosis and post-procedure
      myocardial infarction. Low tensile and radial strengths of polymeric BRS
      contributing to improper strut embedment have been identified as major correlates
      of poor outcomes following BRS implantation. Magnesium has a better
      tensile/radial strength compared with polymeric BRS but it is still far lower
      than cobalt-chromium. Newers innovations utilizing alteration in polymer
      composition and orientation or even newer polymers have focused on attempts to
      reduce strut thickness but may have little effect on tensile/radial strength of
      finished product and therefore may not impact the BRS outcome on long run.
      Currently, newer generation BRS usage may be restricted to suitable low risk
      younger patients with proper vessel preparation and application of technique.

PMID- 29174243
TI  - Evaluation and efficacy of long length Pronova XR Bioabsorbable Polymer stent in
      the treatment of long coronary lesions.
AB  - AIM: The study aims an observational registry of the long and extra-long length
      (>33mm) Pronova XR stents in patients with long coronary lesions (>30mm) in a
      prospective real world study. METHODS AND RESULTS: Current study was conducted at
      Ruby Hall Clinic Pune, between July 2012 and July 2013 including 30 patients who
      underwent PTCA using long and extra-long Pronova XR stents. Among the stents
      used, one stent - 33mm, 2 stents - 38mm, 5 stents - 43mm and 25 stents were of
      48mm in length. In particular average stent length for the study was 46.03mm and
      the average stent diameter was 3.09+/-0.41mm. For this study coronary angioplasty
      was performed using femoral approach and standard practice. Lesions were
      predilated using undersized balloons and study stent was deployed at pressure 7
      26atm. (12.8+/-3.2atm.) The successful delivery of stent at the intended lesion
      with visual residual stenosis less than 50% was defined as Procedural success.
      Follow up studies were conducted for all the patients at 30days, 3 months and 6
      months intervals. The predefined QCA parameters were calculated using Sanders
      Data System QCA plus software (Palo Alto, CA, USA). No procedural complication
      was observed during the whole study. 100% successful stent placement was achieved
      in all patients. Six months clinical follow-up was available for all patients. No
      adverse events (Acute closure, angina, REPCI, MI, death, sub acute stent
      thrombosis) or hospitalization was reported for any of the patients except one.
      The Quantative Coronary Core Lab analysis post 6 months showed well-flowing stent
      with average late lumen loss 0.10mm +/-0.26. CONCLUSION: In patients with long
      coronary lesions and very long length stent implantation series, Pronova XR
      showed excellent in 6 months results. This is for the first time reported that
      use of long length Pronova XR stents has shown so low restenosis rate and absent
      of mortality in six month period. These results offer a new opportunity to single
      long length stenting.

PMID- 29174244
TI  - Left ventricular global longitudinal strain following revascularization in acute
      ST elevation myocardial infarction - A comparison of primary angioplasty and
      Streptokinase-based pharmacoinvasive strategy.
AB  - OBJECTIVE: Tenecteplase-based pharmacoinvasive percutaneous coronary intervention
      (PCI) has been shown to yield outcomes comparable to primary PCI in the setting
      of acute ST elevation myocardial infarction (STEMI). This study was designed to
      compare the efficacy of pharmacoinvasive PCI following successful thrombolysis
      with Streptokinase versus primary PCI in patients with STEMI. METHODOLOGY: We
      conducted a prospective single center observational study in 120 patients with
      STEMI who underwent primary PCI (n=60) and Streptokinase-based pharmacoinvasive
      PCI (n=60). Patients with Killips class 3 or 4 at presentation, and those with
      evidence of failed fibrinolysis were excluded. The primary outcome was LV
      systolic function after angioplasty, as assessed by 2D global longitudinal strain
      (GLS) using speckle tracking echocardiography (STE), as well as 2D LVEF using
      Simpson's biplane method. RESULTS: LV systolic function after PCI was
      significantly lower in the pharmacoinvasive arm as compared to the primary PCI
      arm, both by 2D STE (GLS: -9% vs -11%; p=0.03) and 2D Simpson's biplane method
      (LVEF: 40.7% vs 45.1%; p=0.02). TIMI flow in the culprit vessel prior to
      angioplasty was better in the pharmacoinvasive arm indicating successful
      thrombolysis, whereas post angioplasty flow was not different. There was no in
      hospital mortality in either group. There was a trend toward increased incidence
      of acute kidney injury in the pharmacoinvasive arm. CONCLUSION: LV systolic
      function is significantly better after primary angioplasty as compared to
      pharmacoinvasive PCI following successful thrombolysis with Streptokinase.

PMID- 29174245
TI  - Volume-outcome relationships for transcatheter aortic valve replacement-risk
      adjusted and volume stratified analysis of TAVR outcomes.
AB  - OBJECTIVES: This purpose of the study was to evaluate TAVR outcomes at low,
      intermediate and high volume institutions. BACKGROUND: For the care of complex
      patients, volume-outcome effect is well described. The initial US TAVR experience
      was limited to a few centers of excellence. The impact of institutional volume on
      outcomes after TAVR has not been systematically studied. METHODS: Within the
      Banner Health system, TAVR is performed at 3 institutions-a low volume, an
      intermediate volume and a high volume institution. 181 consecutive patients
      undergoing TAVR within these 3 institutions were the study cohort. To adjust for
      bias and confounders between the 3 groups, risk-adjusted multivariate logistic
      regression and propensity score analysis was performed. The primary endpoint was
      a composite of mortality, dialysis-dependent renal failure, cerebrovascular
      accident, need for new permanent pacemaker and readmission within 30days.
      RESULTS: The primary endpoint was reached in 38.8% of patients at the high volume
      institution and 76.2% of patients at the low volume institution (p<0.01). Having
      a TAVR procedure at a larger volume institution was an independent predictor of
      having improved outcomes (OR 0.33, 95% CI 0.16-0.68; p=0.003). These improved
      outcomes after the TAVR procedure noted at the large volume institution were seen
      in the most complex patients: age >=80years, BMI >30, diabetes, hypertension,
      prior CAD, CKD and NYHA class III/IV heart failure. CONCLUSIONS: High-risk
      patients undergoing TAVR at a large volume institution have better 30-day
      outcomes compared to outcomes at intermediate and low volume centers.

PMID- 29174246
TI  - Incidence of drug-induced torsades de pointes with intravenous amiodarone.
AB  - AIM: To define the incidence, presentation, and outcomes of drug-induced Torsades
      de Pointes (TdP) with intravenous (IV) amiodarone. METHODS: From January 2014 to
      August 2016 a total of 268 patients received IV amiodarone, 142 for ventricular
      tachycardia, 104 for atrial flutter/fibrillation, and 22 for incessant atrial
      tachycardia. A uniform dosing of amiodarone to yield 1gm/day was used in all
      patients. RESULTS: Four of the 268 patients (M:F 1:3) with mean age of
      51.25+9.17years developed pause dependent TdP degenerating to VF, after a mean
      dose of 690+176.63mg, infused over 12+5.88h. The QTc that was 505+9.02ms at the
      time of TdP normalized to 433.75+6.13ms 48-72h after stopping amiodarone. There
      was no immediate or late mortality, and patients are well at 5-10 months of
      follow-up. None of the patients tested positive for LQTS genes. CONCLUSION: The
      incidence of drug-induced TdP with IV amiodarone is about 1.5%. Risk factors
      include female sex, left ventricular dysfunction, electrolyte abnormalities,
      baseline prolonged QTc, concomitant beta-blocker, and digoxin therapy. Amiodarone
      induced TdP has favorable prognosis if recognized and treated promptly, and these
      patients should not receive amiodarone by any route in future.

PMID- 29174247
TI  - Atrial electrical abnormality in patients with Brugada syndrome assessed by
      signal-averaged electrocardiography.
AB  - BACKGROUND: Ventricular fibrillation and atrial fibrillation are well-known
      arrhythmias in patients with Brugada syndrome. This study evaluated the
      characteristics of the atrial arrhythmogenic substrate using the signal-averaged
      electrogram (SAECG) in patients with Brugada syndrome. METHODS: SAECGs were
      performed during normal sinus rhythm in 23 normal volunteers (control group), 21
      patients with paroxysmal atrial fibrillation (PAF; PAF group), and 21 with
      Brugada syndrome (Brugada group). RESULTS: The filtered P wave duration (fPd) in
      the control, Brugada, and PAF groups was 113.9+/-12.9ms, 125.3+/-15.0ms, and
      137.1+/-16.3ms, respectively. The fPd in the PAF group was significantly longer
      compared to that in the control and Brugada groups (p<0.05). The fPd in the
      Brugada group was significantly longer than that in the control group (p<0.05)
      and significantly shorter than that in the PAF group (p<0.05). CONCLUSION:
      Patients with Brugada syndrome had abnormal P waves on the SAECG. The abnormal P
      waves on the SAECG in Brugada syndrome patients may have intermediate
      characteristics between control and PAF patients.

PMID- 29174248
TI  - Electrocardiographic characteristics in young male patients with left primary
      spontaneous pneumothorax estimated by the collins equation.
AB  - OBJECTIVE: To investigate the 12-lead surface electrocardiographic (ECG) findings
      in young male patients with left primary spontaneous pneumothorax (PSP) estimated
      by the Collins equation. METHODS: From 2003 through 2008, 60 young male patients
      who had left PSP and 61 age-matched unaffected males were included for 12-lead
      ECG analyses. The PSP size was estimated by the Collins equation. Those with left
      PSP were divided into two groups: 1) large PSP >=30% (n=37), and 2) small PSP
      <30% (n=23). The ECG in the unaffected was used as the normal control. Baseline
      demographic, anthropometric, and electrocardiographic findings including heart
      rate, P-QRS-T axes, wave intervals, and RS voltages were compared among three
      groups. RESULTS: As compared to the unaffected, patients with left PSP had faster
      heart rate, longer QTc interval, greater QRS and T axes. With regard to RS
      amplitudes, greater R in lead aVR and V1, and deeper S in lead II indicating
      predominant rightward forces, and smaller R in lead I and V3-V6 indicating
      inferior leftward forces were present in patients with left PSP. Of these ECG
      findings, heart rate, S voltage in lead II and R voltage in V1 in the large PSP
      but not in the small PSP had greater values than that in the unaffected group.
      CONCLUSION: Among young male patients with left PSP estimated by the Collins
      method, the ECG showed faster heart beat and predominant rightward forces
      especially for those with large PSP.

PMID- 29174249
TI  - Low interatrial septal pacing: A simple method.
AB  - BACKGROUND: Sinus node disease is associated with widespread structural and
      electrophysiological changes in the atria in addition to abnormalities at the
      sinus node. The atrial conduction disorder in patients with atrial pacing results
      in higher incidence of atrial fibrillation. Studies have shown that low
      interatrial septal pacing is superior to right atrial appendage pacing in
      preventing persistent or permanent atrial fibrillation in these patients.
      However, implantation of active fixation lead in low interatrial septal position
      is difficult and time consuming with conventional stylet, inhibiting application
      of this method in routine practice. METHOD: The technique of implanting atrial
      pacing lead in low interatrial septum with hand-made stylet is presented in this
      study with emphasis on fluoroscopic landmark and electrocardiographic P wave
      pattern. RESULTS: The results indicate acute and short-term success of low
      interatrial septal pacing in 10 patients out of 11 patients without major
      complications. Pacing parameters during implantation and 3 months post procedure
      were within normal limits. CONCLUSION: The initial favorable results of this
      study indicate low interatrial septal pacing with conventional active fixation
      lead using fluoroscopic landmark and electrocardiographic characteristics is
      feasible and reproducible with a simple technique.

PMID- 29174250
TI  - Assessment of right ventriclular systolic function prior to cardiac
      resynchronization therapy: Does it make any difference?
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment for
      patients with advanced heart failure (HF). Nearly 30% of candidates are
      inadequate responders. The benefit of patients with right sided heart failure
      from CRT is still a matter of debate. We examined the effect of CRT on right
      ventricular (RV) dimensions and overall systolic function and whether RV function
      prior to CRT could have an impact on CRT response. METHODS: 94 patients with a
      mean age of 53.7+/-14.6 years including 19 (20%) females, with advanced HF
      (EF<35%, LBBB>120ms, or non-LBBB>150ms, with NYHA -III or ambulatory class IV)
      were enrolled and underwent CRT implantation. Standard two dimensional (2D)
      echocardiography, tissue Doppler imaging, for assessment of Left ventricular (LV)
      end-diastolic (LVEDV), and end-systolic volumes (LVESV), ejection fraction, RV
      maximum basal (RVD basal), maximum mid (RVD mid) transverse, maximum longitudinal
      (RVD long) diameters, TAPSE, fractional area change (FAC), and tricuspid lateral
      annular systolic velocity (S'), in addition to RV global longitudinal strain
      (RVGLS) measured by speckle tracking echocardiography, were done before CRT
      implantation and at the end of the follow up period (5.9+/-1.2 months). Patients
      presenting with reductions of LVESV of >15% were termed volumetric responders for
      further statistical analysis. RESULTS: 63 (67%) cases were volumetric responders.
      Both groups were matched regarding demographic, clinical, ECG, and
      echocardiographic criteria apart from the RV significantly smaller transverse
      diameters and significantly better systolic function parameters in the responders
      group prior to CRT compared to non-responders (NR) group. At the end of the
      follow up, only the responders group had further significant reduction in RV
      basal, mid and longitudinal diameters (33.6+/-7.1 vs 40.7+/-8.6, 21.4+/-4.9 vs
      27+/-6.1, 68.3+/-10.8 vs 81.2+/-15, respectively), p<0.01, together with
      significant improvement in RV systolic performance: FAC (47.7+/-7.3 vs 40.9+/
      6.4), TAPSE (25.2+/-4.6 vs 22.1+/-4.9), S' (15.3+/-2.3 vs 12.8+/-2.3), and GLS
      (26.1+/-2.1 vs 18.5+/-1.6), P<0.01, compared to baseline readings. S' and GLS
      were the only independent predictors of CRT response by multivariate analysis.
      S'>9cm/s, and GLS >12.45% had 100% sensitivity and 70%, 99.7% specificity,
      respectively for prediction of response to CRT. CONCLUSIONS: CRT induces RV
      reverse remodeling and improves RV systolic function particularly in cardiac
      volumetric responders. RV systolic dysfunction before CRT implantation could
      identify patients that might not benefit from CRT thus helping proper patient
      selection and optimizing CRT response.

PMID- 29174251
TI  - Effect of ferric carboxymaltose on hospitalization and mortality outcomes in
      chronic heart failure: A meta-analysis.
AB  - INTRODUCTION: Iron administration especially intravenous iron therapy is
      associated with improvements in exercise capacity and quality of life in patients
      with chronic heart failure (CHF). Our aim was to assess effect of ferric
      carboxymaltose (FCM) on hospitalization and mortality outcomes in CHF. MATERIALS
      AND METHODS: A literature search across PUBMED, Google Scholar and trials
      database www.clinicaltrials.gov was conducted to search for randomized controlled
      trials (till August 2016) comparing FCM to placebo in CHF with or without
      anaemia. Published human studies in English language which reported data on
      mortality and hospitalization rates were included. Primary outcome was rates of
      HF hospitalizations and secondary outcomes were hospitalization due to any
      cardiovascular (CV) cause, death due to worsening HF and any CV death. RESULTS:
      From 17 studies identified, two were included in final analysis (n=760; 455 in
      FCM and 305 in placebo arms). We observed significantly lower rates of
      hospitalization for worsening HF in FCM arm [Risk Ratio (RR) 0.34, 95% confidence
      interval (CI) 0.19, 0.59, p=0.0001] as well as for any CV hospitalizations [RR
      0.49, 95% CI 0.35, 0.70; p<0.0001] (figure). No heterogeneity in studies was seen
      for these two outcomes (I2=0%, p>0.05). No significant treatment effect with FCM
      was noted in mortality from worsening HF (RR 0.41, 95% CI 0.02, 7.36; p=0.55) or
      any CV death (RR 0.80, 95% CI 0.40, 1.57; p=0.51). CONCLUSION: FCM reduces
      hospitalization rates in CHF but may not reduce mortality outcome. This finding
      needs further evaluation in a large, prospective, randomized controlled trial.

PMID- 29174252
TI  - Prevalence and prognostic significance of left ventricular myocardial late
      gadolinium enhancement in severe aortic stenosis.
AB  - BACKGROUND: Myocardial fibrosis occurs in aortic stenosis (AS) as part of the
      hypertrophic response. It can be detected by LGE, which is associated with an
      adverse prognosis in the form of increased mortality and morbidity. OBJECTIVES:
      To assess the prevalence of LGE patterns using cardiac magnetic resonance (CMR)
      in severe AS patients and to study its prognostic significance. METHODS: Patients
      enrolled into the study from June 2012 to November 2014. All the patients
      underwent CMR and various patterns of LGE studied. These patients if symptomatic
      were advised AVR and others were managed conservatively. All patients were
      followed up and watched for outcomes like mortality, heart
      failure/hospitalization for cardiovascular cause, fall in left ventricular
      ejection fraction (LVEF) >=20% and arrhythmia. RESULTS: A total of 109 patients
      (mean age-57.7+/-12.5yrs) underwent CMR with 63 males. These patients were
      followed up for a mean of 13 months. Among 38 patients who underwent AVR, 6 died
      (5-cardiovascular cause, 1-non cardiovascular). 71 patients were managed
      conservatively out of which 18 died (17-cardiovascular cause, 1-non
      cardiovascular cause). LGE patterns were seen in 46 patients (43%); mid
      myocardial enhancement was seen in 31.1% of cases (33 patients). No LGE pattern
      was seen in 57%(63 patients). Basal and mid regions were maximally involved with
      mid myocardial enhancement in 66% & 68.3% respectively. LV ejection fraction
      (p=0.002), peak aortic systolic velocity (p=0.01) and peak aortic systolic
      gradient (p=0.02) were the main predictors of LGE. Main predictors of primary
      outcome were NYHA class [OR- 13.4(2.8-26.1), p<=0.001], age- 62+/-
      9.6yrs(p=0.001), EF simpson-50.9+/-13%(p<= 0.001), LGE[OR 2.8 (1.27
      6.47),p=0.01], number of segments involved [2.37+/-2.1,P<=0.001] & CMR LV mass
      (151.73+/-32gms, p=0.007). LGE predicted heart failure/hospitalization for
      cardiovascular cause [OR- 3.8(1.2-11.9), p=0.01] and fall in LVEF [OR- 5.8(1.5
      22.5), p=0.005]. Patients with LGE had 2.87 times risk of adverse outcomes and
      patients with more than 3 segment LGE involvement had again increased chances for
      adverse outcomes. CONCLUSIONS: LGE was detected by CMR in 43% of patients with
      severe AS. It predicted recurrent heart failure, hospitalization for
      cardiovascular cause and fall in LV ejection fraction. Our study has laid a path
      to larger prospective studies with long term follow up to assess the prognostic
      impact of CMR in patients with severe AS.

PMID- 29174253
TI  - The association of the Syntax score II with carotid intima media thickness and
      epicardial fat tissue.
AB  - AIM: Syntax score II (SSII) is a highly predictive scoring system, which is used
      to improve individualized assessment of patients with complex coronary artery
      disease and facilitates clinical decision making. Surrogate markers [carotid
      intima-media thickness (CIMT), epicardial fat tissue (EFT)] are also used for
      risk assessment, but their relation with SSII is not well established. METHOD: We
      enrolled 543 consecutive patients, who underwent coronary angiography for stable
      angina pectoris and acute coronary syndrome, in the study. SSII was calculated
      for each patient and the patients were divided into two groups as low SSII group
      and high SSII group according to their median SSII. RESULTS: The average age of
      the patients was 61.4 years and 75% of the patients were male. The multivariate
      analysis indicated that only EFT (p: 0,035), CIMT (p:0,04) and Hypertension (HT)
      (p: 0,014) were independently associated with high SSII. DISCUSSION: EFT and
      CIMT, the surrogate markers which can be simply and non-invasively determined,
      are of the independent predictors of high SSII. The inclusion of these parameters
      in the risk classification may provide additional clinical benefit.

PMID- 29174254
TI  - "Correlation of red blood cell distribution width with the severity of coronary
      artery disease-A single center study".
AB  - OBJECTIVE: Coronary Artery Disease (CAD) is the leading cause of morbidity and
      mortality all around the world. We evaluated the correlation of Red blood cell
      Distribution Width (RDW) with the severity of lesion on coronary angiography as
      assessed by Modified Gensini score (MGS) in CAD patients. METHODS: A total of 576
      consecutive patients admitted in Department of Cardiology over a period of one
      year, who underwent coronary angiography after diagnosis of CAD or presence of
      angina like chest pain and/or positive treadmill test were enrolled in the study
      (August 2014-May 2015). Patients were divided into two groups, with CAD (Group A)
      and without CAD (Group B). The RDW Cofficience of variance (RDW CV) and RDW
      standard deviatiton (RDW SD) of each patient, and their correlation with severity
      of CAD was assessed. RESULTS: Of the total 576 patients enrolled, 438 were in
      Group A and 138 were in Group B. The mean age of presentation in Group A and
      Group B was (53.64+/-10.36 vs 49.4+/-9.73)years (p<0.0001). The Male and Female
      ratio overall was 2.42:1. Patients in Group A had significantly elevated RDW CV
      and RDW SD levels compared with those in Group B [(14.59+/-1.04)% vs (13.6+/
      0.68)%, p<0.0001], [(45.78+/-4.76) vs (40.77+/-3.01), p<0.0001 respectively]. A
      significant positive correlation between RDW CV, RDW SD and MGS was noted
      (r=0.33, p<0.0001) (r=0.43, p<0.0001) respectively. On multivariate logistic
      regression analysis, RDW was demonstrated to be an independent predictor for
      angiographic CAD (OR=4.17, 95% CI 3.05-5.69, p<0.0001). On receiver operating
      characteristic curve (ROC) analysis, an RDW value of 14.3% was identified as an
      effective cut off point in diagnosing CAD with a sensitivity of 58.9% and
      specificity of 84.8%. CONCLUSIONS: RDW is an independent predictor of CAD and
      severity of coronary stenosis, suggesting that it can be a readily available
      marker for prediction and severity of CAD.

PMID- 29174255
TI  - The impact of severity of initial illness, determined by SOFA score, and presence
      of anemia on outcomes among patients requiring Extra Corporal Membrane
      Oxygenation (ECMO) support: A single center experience.
AB  - INTRODUCTION: ECMO provides respiratory and circulatory support in critically ill
      patients. In our study, we report on a single center experience with ECMO and aim
      to identify the prognostic markers for survival to discharge from hospital.
      METHODS: A registry was maintained on all patients who underwent ECMO
      implantation from September 2012 till January 2016 at a single institution. The
      collected data was analyzed to identify baseline characteristics, outcomes
      including clinical variables predictive of poor outcome. RESULTS: A total of 29
      patients underwent ECMO implantation. The average age of patients was 42+/
      18years. 59% were males (N=17). 19 cases had a cardiac indication for ECMO (66%)
      while 10 cases had a pulmonary indication (34%). On univariate analysis; presence
      of Multi-organ failure, SOFA score more than 18 and hemoglobin less than 10g/dl
      at baseline and after ECMO removal were associated with increased 30day
      mortality. Pearson correlation with 30day mortality showed a positive correlation
      with MOF (+0.562, p=0.002) and SOFA score >18 (+0.448, p=0.015) and a negative
      correlation with anemia (-0.507, p=0.005). 15 out of the total 29 patients (52%)
      died within 30days of admission. Patients with MOF (log rank: 10.926, p=0.001),
      SOFA score >18 (log rank: 7.758, p=0.005) and hemoglobin <10g/dl (log rank:
      5.595, p=0.018) had decreased survival on 30day follow up. CONCLUSIONS: Although
      the use of ECMO as a last line in the treatment of critical patients refractory
      to conventional treatment measures constitutes an important improvement in their
      care; with 48% overall survival; patient selection and timing of ECMO initiation
      remains challenging. Patients who already had signs of MOF and a high SOFA score
      portended a poor response. Similarly for anemic patients. Hence the importance of
      consideration for ECMO use earlier in course of illness rather than later.
      Screening and aggressive treatment of anemia in those patients may help improve
      the outcomes.

PMID- 29174256
TI  - Mid-term results of correction of Tetralogy of Fallot with absent pulmonary
      valve.
AB  - BACKGROUND: Tetralogy of Fallot and absent pulmonary valve (TOF/APV) is
      associated with significant pulmonary artery dilatation and airway compression.
      METHODS: We performed a retrospective review of 73 consecutive patients who
      underwent repair for TOF/APV between January 2005-August 2015. Mean age was 6.4+/
      5.6years (28days-22years). The right ventricular outflow tract (RVOT) was
      reconstructed using varied techniques. Freedom from RVOT gradients and re
      operation was studied. RESULTS: There were four (5.5%) early deaths, two each in
      infants and older children. Median ICU stay was 2days (range, 1-12days). Mean ICU
      stay for, infants, children and adults, was 6.5+/-6.04, 2.75+/-2.45, and 2.33+/
      1.03days, respectively (p=0.0762). Median hospital stay was 6days (range, 4 to
      15days). Mean hospital stay for, infants and children and adults was 7+/-2,
      6.75+/-2.39, and 6.33+/-1.63days, respectively (p=0.325). Mean follow up was 65+/
      36.6months (median 56 months, range 7-126 months). On follow up echocardiography,
      14 (21.21%) had no pulmonary regurgitation. 21 (31.81%) had mild PR patients, 8
      (12.12%) moderate PR and 19 (28.78%) had severe PR. There were five (7.5%)
      reoperations. Five and ten-year survival was 95%+/-2.12 and 92.3%+/-3.45
      respectively. Freedom from RVOT reoperation was 93+/-2.62% and 89+/-3.87% at 5
      and 10 years. CONCLUSIONS: In contrast to children and adults with TOF/APV,
      infants carry significant early mortality. But the mid-term outcome for patients
      who survive the initial repair of TOF/APV is acceptable. However, these patients
      require constant surveillance and irrespective of the methods of RVOT management,
      the reoperation rates are expected to be high as more of these patients survive
      into adulthood.

PMID- 29174257
TI  - Use of nitroglycerin and verapamil solution by organ bath technique in
      preparation of left internal thoracic artery for coronary artery bypass surgery.
AB  - BACKGROUND: The aim of this prospective study was to compare the effect of
      application of nitroglycerin and verapamil solution (GV) by organ bath technique
      with other methods of applications and solutions on the free blood flow of LITA.
      The technique was not described for in situ graft before. METHOD: The patients
      were randomly assigned to four groups: group I (n_32, GV solution by organ bath
      technique), group II (n_30, papaverine solution by organ bath technique), group
      III (n_29, topical GV solution) or group IV (n_29, topical papaverine solution).
      In each patient, pedicled LITA was harvested; thereafter applied with the
      randomized different methods and solutions. The free flow from the distal end of
      the divided LITA was measured for 15s under controlled hemodynamic conditions
      after harvesting (Flow 1). The flow of LITA was measured again just prior to
      anastomosing the conduit (Flow 2). RESULT: The mean blood flow in LITA was 56.2+/
      5.0ml/min before application of solutions. After application, the mean blood flow
      in group I:102.3+/-7.0ml/min, in group II: 92.7+/-3.4ml/min, and in group III:
      88.6+/-2.2ml/min and in group IV: 81.4+/-2.1. Proportional increases in blood
      flow observed in group I (82.6%)>group II (65.1%)>group III (57.6)>group IV
      (44.8%) (p<0.05). CONCLUSIONS: GV solution by organ bath technique is effective
      and superior in comparison to use of papaverine using organ bath technique or
      topical spray of GV or papaverine solution.

PMID- 29174258
TI  - The design and rationale of the primary angioplasty registry of Kerala.
AB  - BACKGROUND: ST-elevation myocardial infarction (STEMI) continues to be a major
      cause of cardiovascular mortality in Kerala, India. Timely primary percutaneous
      coronary intervention (PCI) is the recommended reperfusion strategy for STEMI.
      There is limited data on the safety, effectiveness, equity and efficiency of
      regional primary PCI services in India. METHODS/DESIGN: The primary angioplasty
      registry of Kerala is a clinician-initiated prospective state-wide longitudinal
      hospital-based registry of patients undergoing primary PCI for STEMI. The
      registry aims to document the efficacy and safety of the real world use of
      primary PCI in Indian patients presenting with STEMI, in order to achieve
      regional adoption of global standard performance indicators. In addition, the
      registry would analyze procedural variations in the performance of primary PCI
      and assess its impact on relevant patient centered outcomes. We plan to enroll
      6000 STEMI patients, undergoing primary PCI, across 48 hospitals. These patients
      would be followed up for a minimum of 1year. CONCLUSIONS: The primary angioplasty
      registry of Kerala would help analyze the quality and outcomes of primary PCI
      services in Kerala, thereby yielding insights that can help limit unacceptable
      procedural variations in the performance of primary PCI. Identifying deviations
      from guideline based therapies can form the basis of quality improvement
      programs, which in turn will enable hospitals to achieve better patient outcomes.

PMID- 29174259
TI  - Cardiac cachexia in sub-Saharan Africa.
AB  - Cachexia is a public health challenge around the Globe but data on prevalence
      rates in developing countries are very scarce. In sub-Saharan Africa wasting
      syndrome is mainly related to malaria, HIV infections, tuberculosis and end-stage
      heart disease and always associated with high-mortality and dismal quality of
      life regardless of age, urban or rural setting. We report two different cases
      affected by cardiac cachexia related to end-stage heart disease. The large age
      gap between patients highlights the current impact of medical services in Uganda
      ranging from low-resource rural settings to urban areas of the capital city under
      epidemiologic transition. The wasting syndrome occurring in both patients
      emphasizes as cachexia remains largely neglected and underestimated in most sub
      Saharan African countries.

PMID- 29174260
TI  - Ambulatory blood pressure monitoring in daily practice.
AB  - Ambulatory blood pressure monitoring is a useful diagnostic tool that still
      underutilized by community physicians. It is a cost effective, diagnostic and
      prognostic tool that had been emphasized by the guidelines.

PMID- 29174261
TI  - Know thy neighbors: The status of cardiac surgery in the South Asian countries
      around India.
AB  - OBJECTIVES: The South Asian neighboring countries of India include Bangladesh,
      Bhutan, Nepal, The Maldives, Pakistan and Sri Lanka. Interestingly all these
      countries possess either a land or a sea border with India and no border among
      themselves. These countries have historic, cultural, ethnic and genetic links
      with India. The paper describes the developmental history and current status of
      cardiac surgery in these countries. METHODS: Thorough search of the printed and
      electronic materials has been made. The authors visited all these countries and
      contacted the eminent surgeons personally or through mails. All the information
      is cross-checked and compiled. Record keeping is not well organized in most of
      these countries. Best information often came from unusual sources like
      Anesthetists' society or the corporate houses. RESULTS: Four of these countries
      Bangladesh, Nepal, Pakistan and Sri Lanka have their cardiac surgical programs.
      Collectively they perform around 38000 cardiac operations a year which is a
      quarter of the cases performed in India. These countries are important sources of
      medical tourism in India which is worth 3 billion US$ of business annually.
      CONCLUSION: When the number of operations per million populations is considered,
      Bangladesh and Nepal are lagging behind India where as Pakistan has a comparable
      figure. Sri Lanka with 265 cardiac operations/million populations has the best
      figures in the region. However when compared with the Western countries even the
      Lankan figures also look quite inadequate.

PMID- 29174262
TI  - Perioperative plasma mitochondrial DNA dynamics and correlation with inflammation
      during infantile cardiopulmonary bypass.
AB  - OBJECTIVE: Numerous studies in animals and humans have demonstrated that
      inflammatory mediators such as tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-6, and IL-8 play a role in cardiopulmonary bypass (CPB), which might affect
      surgical outcomes. Plasma mitochondrial DNA (mtDNA), a recently discovered pro
      inflammatory agent, is released by cells upon insult. This study aimed to detect
      changes in plasma mtDNA levels at different time points after infantile CPB and
      explore its potential association with inflammatory mediators. METHODS: In the
      present study, we analyzed the perioperative plasma mtDNA and inflammatory
      cytokine levels of 48 infants undergoing ventricular septal defect closure. Blood
      samples were collected before aortic cross-clamping (T1), at the end of CPB (T2),
      and 6h (T3), 12h (T4), and 24h (T5) post-CPB. Reverse transcription-polymerase
      chain reaction and specific enzyme-linked immunosorbent assay were used to
      quantify the plasma mtDNA and inflammatory cytokines, respectively. Bivariate
      correlation analysis was used to determine the correlations between plasma mtDNA
      and inflammatory cytokines. RESULTS: Plasma mtDNA levels increased at T2 and
      peaked at T3. Significant positive correlations were found between peak plasma
      mtDNA (at T3) and several inflammatory biomarkers, including IL-6 (at T3)
      (r=0.62, P<0.001), IL-8 (at T2) (r=0.53, P<0.001), and TNF-alpha (at T3) (r=0.61,
      P<0.001). CONCLUSION: Here we report that mtDNA may participate in a systemic
      inflammatory response to CPB.

PMID- 29174263
TI  - First ever transmitral valve in valve replacement in India.

PMID- 29174264
TI  - Flap like structure at SVC orifice: SVC valve or atypical chiari network?

PMID- 29174265
TI  - Sub-acute stent thrombosis secondary to ticagrelor resistance-Myth or reality!!

PMID- 29174266
TI  - Coronary artery disease - The greatest threat to women's health.

PMID- 29174267
TI  - Coronary artery disease in women.

PMID- 29174268
TI  - SMS campaign - Can it facilitate prevention of cardiovascular diseases in India?

PMID- 29174269
TI  - Letter to Editor.

PMID- 29174270
TI  - Are e-cigarettes beneficial for public health: Hume's guillotine - The debate
      continues?
AB  - Cigarette smoking is the most common preventable cause of death which has led to
      a search for healthier alternatives to tobacco smoke. Electronic cigarettes are
      devoid of many harmful constituents found in cigarette smoke and are therefore
      being positioned as safer alternative to tobacco smoke. The carcinogenic
      potential may be of lower magnitude compared with cigarette smoke, but it is
      still there. The use of e-cigarettes, however, is fairly new, so its long-term
      effects are still unknown. Moreover, they continue to posses the cardiovascular
      side-effects and are certainly as addicting. Thus on one hand while their
      substitution could lead to reduction of some side-effects of tobacco smoke, its
      use may be just shifting the modality of addiction and will be unlikely to lead
      to total abstinence from tobacco products. On the other hand there is a fear that
      its use could lead to loosening of the taboo currently associated with use of
      tobacco products and so the benefits of years of advocacy to ban tobacco products
      might be lost. Thus currently the scientific community is divided about role of e
      cigarettes.

PMID- 29174272
TI  - Editorial Comment.

PMID- 29174271
TI  - Effects of pulsed electromagnetic field therapy at different frequencies and
      durations on rotator cuff tendon-to-bone healing in a rat model.
AB  - BACKGROUND: Rotator cuff tears affect millions of individuals each year, often
      requiring surgical intervention. However, repair failure remains common. We have
      previously shown that pulsed electromagnetic field (PEMF) therapy improved tendon
      to-bone healing in a rat rotator cuff model. The purpose of this study was to
      determine the influence of both PEMF frequency and exposure time on rotator cuff
      healing. METHODS: Two hundred ten Sprague-Dawley rats underwent acute bilateral
      supraspinatus injury and repair followed by either Physio-Stim PEMF or high
      frequency PEMF therapy for 1, 3, or 6 hours daily. Control animals did not
      receive PEMF therapy. Mechanical and histologic properties were assessed at 4, 8,
      and 16 weeks. RESULTS: Improvements in different mechanical properties at various
      endpoints were identified for all treatment modalities when compared with
      untreated animals, regardless of PEMF frequency or duration. Of note, 1 hour of
      Physio-Stim treatment showed significant improvements in tendon mechanical
      properties across all time points, including increases in both modulus and
      stiffness as early as 4 weeks. Collagen organization improved for several of the
      treatment groups compared with controls. In addition, improvements in type I
      collagen and fibronectin expression were identified with PEMF treatment. An
      important finding was that no adverse effects were identified in any mechanical
      or histologic property. CONCLUSIONS: Overall, our results suggest that PEMF
      therapy has a positive effect on rat rotator cuff healing for each
      electromagnetic fundamental pulse frequency and treatment duration tested in this
      study.

PMID- 29174273
TI  - Placentophagy's effects on mood, bonding, and fatigue: A pilot trial, part 2.
AB  - BACKGROUND: Human maternal placentophagy is gaining popularity among a growing
      number of women who believe it provides maternal benefits, including prevention
      of postpartum blues/depression, improved maternal bonding, and reduced fatigue.
      METHODS: We conducted a randomized, double-blind, placebo-controlled pilot study
      (N=27) in which participants consumed either their processed, encapsulated
      placenta (n=12), or similarly prepared placebo (n=15). Maternal mood, bonding,
      and fatigue were assessed via validated scales across four time points during
      late pregnancy and early postpartum. Psychometric data were analyzed for changes
      between and within both groups over time. RESULTS: No significant main effects
      related to maternal mood, bonding, or fatigue were evident between placenta and
      placebo group participants. However, examination of individual time points
      suggested that some measures had specific time-related differences between
      placenta and placebo groups that may warrant future exploration. Though
      statistical significance should not be interpreted in these cases, we did find
      some evidence of a decrease in depressive symptoms within the placenta group but
      not the placebo group, and reduced fatigue in placenta group participants at the
      end of the study compared to the placebo group. CONCLUSIONS: No robust
      differences in postpartum maternal mood, bonding, or fatigue were detected
      between the placenta and placebo groups. This finding may be especially important
      for women considering maternal placentophagy as a 'natural' (i.e., non
      pharmacological) means of preventing or treating blues/depression. Given the
      study limitations, these findings should be interpreted as preliminary. Small,
      time-related improvements in maternal mood and lower fatigue post-supplementation
      among placenta group participants may warrant further research.

PMID- 29174274
TI  - Effects of placentophagy on maternal salivary hormones: A pilot trial, part 1.
AB  - BACKGROUND: Recent studies show that human placenta, processed and encapsulated
      for postpartum consumption, contains a host of trace minerals and hormones that
      could conceivably affect maternal physiology. Our objective was to investigate
      whether salivary hormone concentrations of women ingesting their own encapsulated
      placenta during the early postpartum differed from those of women consuming a
      placebo. METHODS: Randomly assigned participants (N=27) were given a supplement
      containing either their dehydrated and homogenized placenta (n=12), or placebo
      (n=15). Saliva samples were collected during late pregnancy and early postpartum.
      Samples of participants' processed placenta, and the encapsulated placebo, were
      also collected. Hormone analyses were conducted on all samples utilizing liquid
      chromatography-tandem mass spectrometry. RESULTS: There were no significant
      differences in salivary hormone concentrations between the placenta and placebo
      groups post-supplementation that did not exist pre-supplementation. There were,
      however, significant dose-response relationships between the concentration of all
      15 detected hormones in the placenta capsules and corresponding salivary hormone
      measures in placenta group participants not seen in the placebo group. The higher
      salivary concentrations of these hormones in the placenta group reflects the
      higher concentrations of these hormones in the placenta supplements, compared to
      the placebo. CONCLUSIONS: Some hormones in encapsulated placenta lead to small
      but significant differences in hormonal profiles of women taking placenta
      capsules compared to those taking a placebo, although these dose-response changes
      were not sufficient to result in significant hormonal differences between groups.
      Whether modest hormonal changes due to placenta supplementation are associated
      with therapeutic postpartum effects, however, awaits further investigation.

PMID- 29174276
TI  - Insufficient evidence about long-term success of glass-fiber versus titanium
      posts in severely damaged teeth owing to large proportion of participants lost to
      follow-up in a randomized clinical trial.

PMID- 29174275
TI  - [Sense of coherence and subjective overload, anxiety and depression in caregivers
      of elderly relatives].
AB  - OBJECTIVE: To analyze the relationship between the sense of coherence and
      subjective overload, anxiety and depression in caregivers of dependent elderly
      relatives. METHOD: Cross-sectional study in an area of the province of Jaen
      (Andalusia, Spain) with a probabilistic sample of 132 caregivers of dependent
      elderly. MAIN MEASURES: sense of coherence (Life Orientation Questionnaire),
      subjective burden (Caregiver Strain Index), anxiety and depression (Goldberg
      Scale), objective burden (Dedication to Care Scale), sex and kinship. Main
      analyses: bivariate analysis using the Pearson correlation coefficient and
      multivariate analysis using multiple linear regression. RESULTS: Most of the
      caregivers studied were women (86.4%), daughter or son of the care recipient
      (74.2%) and shared home with the latter (69.7%). When controlling for objective
      burden, sex and kinship, we found that the sense of coherence was inversely
      related to subjective burden (beta = -0.46; p <0.001), anxiety (beta = -0.57; p =
      0.001) and depression (beta = -0.66; p <0.001). CONCLUSIONS: The sense of
      coherence might be an important protective factor of subjective burden, anxiety
      and depression in caregivers of dependent elderly relatives.

PMID- 29174277
TI  - High proportion of implant and prostheses survive after 5 years in patients
      treated with the All-on-4 strategy in the maxilla.

PMID- 29174278
TI  - Use of short implants or long implants with bone grafting may not result in
      different outcomes.

PMID- 29174279
TI  - Uncertainty about whether periodontal therapy improves oral health-related
      quality of life owing to serious limitations in systematic review addressing this
      question.

PMID- 29174280
TI  - Physician staffing needs in critical care departments.
AB  - Departments of Critical Care Medicine are characterized by high medical
      assistance costs and great complexity. Published recommendations on determining
      the needs of medical staff in the DCCM are based on low levels of evidence and
      attribute excessive significance to the structural/welfare approach (physician-to
      beds ratio), thus generating incomplete and minimalistic information. The Spanish
      Society of Intensive Care Medicine and Coronary Units established a Technical
      Committee of experts, the purpose of which was to draft recommendations regarding
      requirements for medical professionals in the ICU. The Technical Committee
      defined the following categories: 1) Patient care-related aspects; 2) Activities
      outside the ICU; 3) Patient safety and clinical management aspects; 4) Teaching;
      and 5) Research. A subcommittee was established with experts pertaining to each
      activity category, defining criteria for quantifying the percentage time of the
      intensivists dedicated to each task, and taking into account occupational
      category. A quantitative method was applied, the parameters of which were the
      number of procedures or tasks and the respective estimated indicative times for
      patient care-related activities within or outside the context of the DCCM, as
      well as for teaching and research activities. Regarding non-instrumental
      activities, which are more difficult to evaluate in real time, a matrix of range
      versus productivity was applied, defining approximate percentages according to
      occupational category. All activities and indicative times were tabulated, and a
      spreadsheet was created that modified a previously designed model in order to
      perform calculations according to the total sum of hours worked and the hours
      stipulated in the respective work contract. The competencies needed and the tasks
      which a Department of Critical Care Medicine professional must perform far exceed
      those of a purely patient care-related character, and cannot be quantified using
      structural criteria. The method for describing the 5 types of activity, the
      quantification of specific tasks, the respective times needed for each task, and
      the generation of a spreadsheet led to the creation of a management instrument.

PMID- 29174281
TI  - Controversies and recommendations regarding sentinel lymph node biopsy in primary
      breast cancer: A comprehensive review of current data.
AB  - In primary breast cancer, sentinel lymph node biopsy has been established as the
      gold standard for regional axillary staging. A robust body of randomized data
      support its accuracy and safety in patients with early, clinically node negative
      disease. However, the role of SLNB remains debatable in various patient
      subgroups, and recent advances in histopathology, dedicated axillary ultrasound
      imaging and chemotherapy regimens, put its role under a new perspective. Herein,
      we review the current literature data on the indications for SLNB and discuss the
      challenges in management germane to special patient subgroups and patterns of
      disease. We also present emerging data on the optimal management of the SLN+
      patient, in light of recent trials challenging the dogma of completion axillary
      dissection after a positive sentinel node biopsy.

PMID- 29174282
TI  - Intranasal dexmedetomidine in termination of first trimester pregnancy of suction
      evacuation.
AB  - BACKGROUND AND AIM: Deep sedation without intubation for termination of first
      trimester pregnancy of suction evacuation entails use of sedatives such as
      propofol or a combination of propofol and sulfentanil, with unwanted
      complications. Dexmedetomidine is an alpha2-adrenoreceptor agonist which provides
      sedation, anxiolysis and analgesia, without any of the complications associated
      with the popular sedatives. METHODS: A total number of 90 patients were
      randomized to three groups: 1. group P, treated with intranasal saline,
      intravenous saline and propofol; 2. group DP, treated with intranasal
      dexmedetomidine, intravenous saline and propofol; and 3. group SP, treated with
      intranasal saline, intravenous sulfentanil and propofol. The primary outcome was
      the consumption of propofol, and the secondary outcomes were numeric rating scale
      (NRS) anxiety score, NRS pain score of uterine cramping, amount of blood loss,
      use of oxytocin and NRS satisfaction scores of obstetric and gynecological
      (ob/gyn) physicians and patients. RESULTS: The consumption of propofol, NRS pain
      score of uterine cramping after surgery, NRS anxiety score, and amount of blood
      loss in group DP were significantly lower than those in group P and group SP.
      Ob/gyn physicians' satisfaction score in group DP was significantly higher
      compared with group SP and group P. CONCLUSION: Sedation with intranasal
      dexmedetomidine (1 MUg/kg) provided effective analgesia and anxiolysis, reduced
      consumption of propofol and lower blood loss in termination of first trimester
      pregnancy of suction evacuation. Compared with propofol or the combination of
      propofol and sulfentanil, intranasal dexmedetomidine was associated with higher
      satisfaction score of ob/gyn physicians. No unforeseen perioperative respiratory
      and cardiovascular adverse events occurred. REGISTRY NUMBER FOR CLINICAL TRIALS:
      ChiCTR-IPR-14005654.

PMID- 29174283
TI  - Response to the Letter to the Editor-in-Chief on Manuscript Entitled: Transbulbar
      B-Mode Sonography in Multiple Sclerosis: Clinical and Biological Relevance.

PMID- 29174284
TI  - Early benefits of sacubitril/valsartan: Hype or hope.

PMID- 29174286
TI  - Structural basis of activation of mammalian heme peroxidases.
AB  - The mammalian heme peroxidases including lactoperoxidase (LPO), myeloperoxidase
      (MPO), eosinophil peroxidase (EPO) and thyroid peroxidase (TPO) contain a
      covalently linked heme moiety. Initially, it was believed that the heme group was
      fully cross-linked to protein molecule through at least two ester linkages
      involving conserved glutamate and aspartate residues with 1-methyl and 5-methyl
      groups of pyrrole rings A and C respectively. In MPO, an additional sulfonium ion
      linkage was present between 2-vinyl group of pyrrole ring A of the heme moiety
      and a methionine residue of the protein. These linkages were formed through a
      self processing mechanism. Subsequently, biochemical studies indicated that the
      heme moiety was partially attached to protein. The recent structural studies have
      shown that the covalent linkage involving glutamate and 1-methyl group of pyrrole
      ring of heme moiety was partially formed. When glutamate is not covalently linked
      to heme moiety, its side chain occupies a position in the substrate binding site
      on the distal heme side and blocks the substrate binding site leading to
      inactivation. However, an exposure to H2O2 converts it to a fully covalently
      linked state with heme. Thus in mammalian heme peroxidases, the Glu-heme linkage
      is essential for catalytic action.

PMID- 29174285
TI  - Longitudinal association among endothelial function, arterial stiffness and
      subclinical organ damage in hypertension.
AB  - OBJECTIVES: To examine the longitudinal mutual association between endothelial
      dysfunction and arterial stiffness, and also to determine which of the two
      variables was more closely associated with the progression of subclinical organ
      damage. METHODS: The brachial-ankle pulse wave velocity (baPWV), carotid intima
      media thickness (CIMT), estimated glomerular filtration rate, microalbuminuria
      and flow-mediated vasodilatation of the brachial artery (FMD) were measured three
      times at 1.5-year intervals in 674 Japanese patients receiving antihypertensive
      treatment. RESULTS: The change of the baPWV during the study period was larger in
      the subjects with baseline FMD values in the lowest tertile as compared to those
      with baseline FMD values in the highest tertile. The change of the CIMT was
      smaller in the subjects with baseline baPWV values in the lowest tertile than in
      those with baseline baPWV values in the highest tertile. After the adjustment,
      the FMD value at the baseline was inversely associated with the baPWV at the end
      of the study period (beta=-0.07, p=0.01), although, the reverse association was
      not significant. The baPWV, but not the FMD value, at the baseline was associated
      with the CIMT (beta=0.06, p=0.04) measured at the end of the study period.
      CONCLUSIONS: In hypertension, endothelial dysfunction was associated with the
      progression of arterial stiffness, although the reverse association was not
      confirmed. The increased arterial stiffness rather than endothelial dysfunction
      may be more closely associated with the progression of atherosclerotic vascular
      damage, and the endothelial dysfunction-arterial stiffness-atherosclerosis
      continuum may be important in hypertension.

PMID- 29174287
TI  - On the use of on-cow accelerometers for the classification of behaviours in dairy
      barns.
AB  - Analysing behaviours can provide insight into the health and overall well-being
      of dairy cows. Automatic monitoring systems using e.g., accelerometers are
      becoming increasingly important to accurately quantify cows' behaviours as the
      herd size increases. The aim of this study is to automatically classify cows'
      behaviours by comparing leg- and neck-mounted accelerometers, and to study the
      effect of the sampling rate and the number of accelerometer axes logged on the
      classification performances. Lying, standing, and feeding behaviours of 16
      different lactating dairy cows were logged for 6h with 3D-accelerometers. The
      behaviours were simultaneously recorded using visual observation and video
      recordings as a reference. Different features were extracted from the raw data
      and machine learning algorithms were used for the classification. The
      classification models using combined data of the neck- and the leg-mounted
      accelerometers have classified the three behaviours with high precision (80-99%)
      and sensitivity (87-99%). For the leg-mounted accelerometer, lying behaviour was
      classified with high precision (99%) and sensitivity (98%). Feeding was
      classified more accurately by the neck-mounted versus the leg-mounted
      accelerometer (precision 92% versus 80%; sensitivity 97% versus 88%). Standing
      was the most difficult behaviour to classify when only one accelerometer was
      used. In addition, the classification performances were not highly influenced
      when only X, X and Z, or Z and Y axes were used for the classification instead of
      three axes, especially for the neck-mounted accelerometer. Moreover, the accuracy
      of the models decreased with about 20% when the sampling rate was decreased from
      1Hz to 0.05Hz.

PMID- 29174288
TI  - [Update on the respiratory management of patients with chronic neuromuscular
      disease].
AB  - BACKGROUND: Neuromuscular diseases include a wide range of conditions that may
      involve potentially life-threatening respiratory complications (infection,
      respiratory failure). SURVEILLANCE AND PULMONARY FUNCTION TESTS: For patients
      with neuromuscular diseases, clinical assessment of respiratory function and
      regular pulmonary function tests are needed to screen for nocturnal respiratory
      disorders, weakness of the diaphragm and potential restrictive disorders and/or
      chronic hypercapnic respiratory insufficiency, possibly with couch deficiency.
      MANAGEMENT OF NOCTURNAL RESPIRATORY DISORDERS AND CHRONIC RESPIRATORY FAILURE:
      Nocturnal respiratory assistance is an important phase of care for nocturnal
      respiratory disorders and chronic respiratory failure. This may involve
      continuous positive airway pressure, adaptative servo-ventilation or non-invasive
      ventilation with a facial or nasal mask. As needed, diurnal assistance may be
      proposed by mouthpiece ventilation. Should non-invasive ventilation prove
      insufficient, or if significant swallowing disorders or recurrent bronchial
      obstruction develop, or in case of prolonged intubation, tracheotomy may be
      required. LOWER AIRWAY OBSTRUCTION: In case of lower airway infection with
      ineffective cough, physical therapy, associated with air stacking, intermittent
      positive pressure breathing or mechanical in-exsufflation may be proposed.
      PATIENT-CENTERED MANAGEMENT: Care for swallowing disorders, nutritional
      counseling (cachexia, obesity), vaccinations and therapeutic education are
      integral elements of patient-centered management aiming to prevent the negative
      impact of infection and to manage respiratory failure of chronic neuromuscular
      disease.

PMID- 29174289
TI  - Derivation and Validation of the Emergency Medical Stroke Assessment and
      Comparison of Large Vessel Occlusion Scales.
AB  - BACKGROUND: This study aims to develop a simple scale to identify patients with
      prehospital stroke with large vessel occlusion (LVO), without losing sensitivity
      for other stroke types. METHODS: The Emergency Medical Stroke Assessment (EMSA)
      was derived from the National Institutes of Health Stroke Scale (NIHSS) items and
      validated for prediction of LVO in a separate cohort. We compared the EMSA with
      the 3-item stroke scale (3I-SS), Cincinnati Prehospital Stroke Severity Scale (C
      STAT), Rapid Arterial oCclusion Evaluation (RACE) scale, and Field Assessment
      Stroke Triage for Emergency Destination (FAST-ED) for prediction of LVO and
      stroke. We surveyed paramedics to assess ease of use and interpretation of
      scales. RESULTS: The combination of gaze preference, facial asymmetry,
      asymmetrical arm and leg drift, and abnormal speech or language yielded the EMSA.
      An EMSA less than 3, 75% sensitivity, and 50% specificity significantly reduced
      the likelihood of LVO (LR- = .489, 95% confidence interval .366-0.637) versus 3I
      SS less than 4 (.866, .798-0.926). A normal EMSA, 93% sensitivity, and 47%
      specificity significantly reduced the likelihood of stroke (LR- = .142, .068
      0.299) versus 3I-SS (.476, .330-0.688) and C-STAT (.858, .717-1.028). EMSA was
      rated easy to perform by 72% (13 of 18) of paramedics versus 67% (12 of 18) for
      FAST-ED and 6% (1 of 18) for RACE (chi2 = 27.25, P < .0001), and easy to
      interpret by 94% (17 of 18) versus 56% (10 of 18) for FAST-ED and 11% (2 of 18)
      for RACE (chi2 = 21.13, P < .0001). CONCLUSIONS: The EMSA has superior abilities
      to identify LVO versus 3I-SS and stroke versus 3I-SS and C-STAT. The EMSA has
      similar ability to triage patients with stroke compared with the FAST-ED and
      RACE, but is simpler to perform and interpret.

PMID- 29174290
TI  - Associations of Mitral and Aortic Valve Calcifications with Complex Aortic
      Atheroma in Patients with Embolic Stroke of Undetermined Source.
AB  - BACKGROUND: This study investigated the associations of mitral and aortic valve
      calcification with complex aortic atheroma among patients with embolic stroke of
      undetermined source. METHODS: We included 52 consecutive patients (mean age 58.1
      years; 75.0% male) with embolic stroke of undetermined source. Mitral annular
      calcification, aortic annular calcification, and aortic valve sclerosis were
      assessed by transthoracic echocardiography. Complex aortic atheroma was assessed
      by transesophageal echocardiography and was defined as plaque protruding greater
      than or equal to 4 mm into the lumen or with ulcerated or mobile components.
      RESULTS: Ten patients (19.2%) had complex aortic atheroma. Patients with and
      without complex aortic atheroma showed significant differences in terms of
      hypertension (80.0% versus 38.1%, P = .017), dyslipidemia (90.0% versus 31.0%, P
      <.01), chronic kidney disease (60.0% versus 14.3%, P <.01), previous coronary
      artery disease (30.0% versus 4.8%, P = .013), prior stroke (40.0% versus 7.1%, P
      <.01), left atrial dimension (4.0 cm versus 3.6 cm, P = .023), aortic valve
      sclerosis (80.0% versus 26.2%, P <.01), aortic valve calcification (aortic
      annular calcification or aortic valve sclerosis) (80.0% versus 26.0%, P <.01),
      and left-sided valve calcification (mitral annular calcification or aortic
      annular calcification or aortic valve sclerosis) (80.0% versus 28.6%, P <.01). In
      multivariate analysis, left-sided valve calcification was independently
      associated with complex aortic atheroma (odds ratio 4.1, 95% confidence interval
      1.3-26.1, P = .049). CONCLUSIONS: Mitral or aortic valve calcification detected
      by transthoracic echocardiography can be a useful marker for predicting complex
      aortic atheroma in patients with embolic stroke of undetermined source.

PMID- 29174291
TI  - Rising incidence of heart failure demands action.

PMID- 29174293
TI  - Improvements in the CRISPR/Cas9 system for high efficiency gene disruption in
      Trypanosoma cruzi.
AB  - Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects
      millions of individuals around the world. Although it has been known for more
      than a century, the study of T. cruzi has been a challenge, particularly due to
      the scarcity of tools for genome inquiries. Recently, strategies have been
      described allowing gene disruption in T. cruzi by the CRISPR/Cas9 nuclease
      system. Although these strategies demonstrated success in deleting some genes,
      several aspects could be improved to increase the efficiency of the CRISPR/Cas9
      system in T. cruzi. Here, we report a strategy, based on adaptations and
      improvements of the two previously described systems, that results in efficient
      gene disruption that can be applied to any target, including the study of
      essential genes.

PMID- 29174292
TI  - Temporal trends and patterns in heart failure incidence: a population-based study
      of 4 million individuals.
AB  - BACKGROUND: Large-scale and contemporary population-based studies of heart
      failure incidence are needed to inform resource planning and research
      prioritisation but current evidence is scarce. We aimed to assess temporal trends
      in incidence and prevalence of heart failure in a large general population cohort
      from the UK, between 2002 and 2014. METHODS: For this population-based study, we
      used linked primary and secondary electronic health records of 4 million
      individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is
      representative of the UK population in terms of age and sex. Eligible patients
      were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec
      31, 2014, had an acceptable record according to CPRD quality control, were
      approved for CPRD and Hospital Episodes Statistics linkage, and were registered
      with their general practice for at least 12 months. For patients with incident
      heart failure, we extracted the most recent measurement of baseline
      characteristics (within 2 years of diagnosis) from electronic health records, as
      well as information about comorbidities, socioeconomic status, ethnicity, and
      region. We calculated standardised rates by applying direct age and sex
      standardisation to the 2013 European Standard Population, and we inferred crude
      rates by applying year-specific, age-specific, and sex-specific incidence to UK
      census mid-year population estimates. We assumed no heart failure for patients
      aged 15 years or younger and report total incidence and prevalence for all ages
      (>0 years). FINDINGS: From 2002 to 2014, heart failure incidence (standardised by
      age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per
      100 000 person-years; adjusted incidence ratio 0.93, 95% CI 0.91-0.94). However,
      the estimated absolute number of individuals with newly diagnosed heart failure
      in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due
      to an increase in population size and age. The estimated absolute number of
      prevalent heart failure cases in the UK increased even more, by 23% (from 750 127
      to 920 616). Over the study period, patient age and multi-morbidity at first
      presentation of heart failure increased (mean age 76.5 years [SD 12.0] to 77.0
      years [12.9], adjusted difference 0.79 years, 95% CI 0.37-1.20; mean number of
      comorbidities 3.4 [SD 1.9] vs 5.4 [2.5]; adjusted difference 2.0, 95% CI 1.9
      2.1). Socioeconomically deprived individuals were more likely to develop heart
      failure than were affluent individuals (incidence rate ratio 1.61, 95% CI 1.58
      1.64), and did so earlier in life than those from the most affluent group
      (adjusted difference -3.51 years, 95% CI -3.77 to -3.25). From 2002 to 2014, the
      socioeconomic gradient in age at first presentation with heart failure widened.
      Socioeconomically deprived individuals also had more comorbidities, despite their
      younger age. INTERPRETATION: Despite a moderate decline in standardised incidence
      of heart failure, the burden of heart failure in the UK is increasing, and is now
      similar to the four most common causes of cancer combined. The observed
      socioeconomic disparities in disease incidence and age at onset within the same
      nation point to a potentially preventable nature of heart failure that still
      needs to be tackled. FUNDING: British Heart Foundation and National Institute for
      Health Research.

PMID- 29174294
TI  - The Kv7/KCNQ channel blocker XE991 protects nigral dopaminergic neurons in the 6
      hydroxydopamine rat model of Parkinson's disease.
AB  - The excitability of dopaminergic neurons in the substantia nigra pars compacta
      (SNc) that supply the striatum with dopamine (DA) determines the function of the
      nigrostriatal system for motor coordination. We previously showed that 4
      pyridinylmethyl-9(10H)-anthracenone (XE991), a specific blocker of Kv7/KCNQ
      channels, enhanced the excitability of nigral DA neurons and resulted in
      attenuation of haloperidol-induced catalepsy in a Parkinson's disease (PD) rat
      model. However, whether XE991 exhibits neuroprotective effects towards DA neuron
      degeneration remains unknown. The aim of this study was to investigate the
      effects of Kv7/KCNQ channel blocker, XE991, on 6-hydroxydopamine (6-OHDA)-induced
      nigral DA neuron degeneration and motor dysfunction. Using immunofluorescence
      staining and western blotting, we showed that intracerebroventricular
      administration of XE991 prevented the 6-OHDA-induced decrease in tyrosine
      hydroxylase (TH)-positive neurons and TH protein expression in the SNc. High
      performance liquid chromatography with electrochemical detection (HPLC-ECD) also
      revealed that XE991 partly restored the levels of DA and its metabolites in the
      striatum. Moreover, XE991 decreased apomorphine (APO)-induced contralateral
      rotations, enhanced balance and coordination, and attenuated muscle rigidity in 6
      OHDA-treated rats. Importantly, all neuroprotective effects by XE991 were
      abolished by co-application of Kv7/KCNQ channel opener retigabine and XE991.
      Thus, Kv7/KCNQ channel inhibition by XE991 can exert neuroprotective effects
      against 6-OHDA-induced degeneration of the nigrostriatal DA system and motor
      dysfunction.

PMID- 29174295
TI  - [Lisch corneal dystrophy: Astigmatism that blurs].

PMID- 29174297
TI  - The N-terminal pro brain natriuretic peptide as a predictor of mortality in
      patients with community acquired pneumonia.

PMID- 29174296
TI  - [Reliability and reproducibility of introcular pressure (IOP) measurement with
      the Icare(r) Home rebound tonometer (model TA022) and comparison with Goldmann
      applanation tonometer in glaucoma patients].
AB  - PURPOSE: The Icare(r) Home tonometer is a new rebound tonometer, developed for
      intraocular pressure (IOP) self-monitoring. The main objective of our study was
      to evaluate the reliability and reproducibility of measurements taken with the
      Icare(r) Home tonometer in glaucoma patients compared to the Goldmann applanation
      tonometer. A secondary objective was to investigate factors that could influence
      the reproducibility of these measurements. MATERIALS AND METHODS: Fifty-two
      glaucoma patients were included in this prospective, non-randomized, monocentric
      study. IOP measurements were performed on the right eye and then on the left eye
      in the following order (3 measurements of IOP for each method): air tonometer (T
      Air), Icare(r) Home tonometer by the patient (RT-P), Icare(r) Home tonometer by
      an ophthalmologist (RT-O), Goldmann applanation tonometer (GAT). RESULTS: Forty
      four patients (85%) managed to take their IOP on both eyes with the Icare(r) Home
      tonometer. Mean IOPs were 14.35+/-3.93mmHg (T-Air), 13.43+/-4.65mmHg (RT-P),
      14.13+/-4.29mmHg (RT-O), 14.74+/-3.84mmHg (GAT). The intraclass correlation
      indices (ICC) on the 3 repeated IOP measurements were 0.924, 0.872, 0.947 and
      0.957, respectively. Bland-Altman analysis found a mean difference (bias) between
      GAT and RT-P, between GAT and RT-O, and between RT-O and RT-P, respectively, of
      1.31, 0.61 and 0.70mmHg, with a 95% confidence interval of -3.34 to 5.96, -3.91
      to 5.14 and -3.44 to 4.84mmHg, respectively. The reproducibility of the
      measurements taken with the Icare(r) Home tonometer did not vary according to
      corneal thickness or age of the patients. CONCLUSION: The Icare(r) Home tonometer
      provides reliable and reproducible IOP values in glaucoma patients, although it
      appears to slightly underestimate the IOP measurements compared to the Goldmann
      applanation tonometer.

PMID- 29174298
TI  - Predatory journals: a serious complication in the scholarly publishing landscape.

PMID- 29174299
TI  - How do professional Australian Football League (AFL) players utilise social media
      during periods of injury? A mixed methods analysis.
AB  - OBJECTIVES: The objective of this study was to explore how social media is used
      by a population of injured professional athletes, by comparing the content and
      frequency of posts on social media, pre and post-injury. DESIGN: A retrospective
      mixed methods design was utilised. METHODS: Professional Australian Football
      League (AFL) players, injured during the 2015 season, were included in the study.
      Publicly accessible social media profiles for these players were identified on
      Twitter and Instagram. All posts published on verified profiles, from four weeks
      prior to injury until return to play, were extracted. Thematic analysis was used
      to investigate the content of these posts, while univariate and multivariate
      linear regression was used to investigate the frequency of posts during this time
      period. RESULTS: Two reoccurring themes were identified exclusively post-injury;
      'supporting team from the sideline' and 'sharing information about injury and
      rehabilitation'. The frequency of total posts did not differ significantly pre
      and post-injury, but the frequency of injury related posts increased in the
      immediate post-injury phase, then decreased between 4-8 weeks and 8-12 weeks post
      injury. The frequency of injury related posts was higher with more severe
      injuries. CONCLUSIONS: The findings of this study suggest that injured players
      use social media to seek social support from their followers, especially in the
      immediate post-injury period and after sustaining a severe injury. The role of
      social media in injury rehabilitation may warrant further investigation, to
      determine if it could be used to facilitate return to play.

PMID- 29174300
TI  - Long-term treatment with metformin in type 2 diabetes and methylmalonic acid:
      Post hoc analysis of a randomized controlled 4.3year trial.
AB  - AIMS: Metformin treatment is associated with a decrease of serum vitamin B12, but
      whether this reflects tissue B12 deficiency is controversial. We studied the
      effects of metformin on serum levels of methylmalonic acid (MMA), a biomarker for
      tissue B12 deficiency, and on onset or progression of neuropathy. METHODS: In the
      HOME trial, 390 insulin-treated patients with type 2 diabetes were treated with
      metformin or placebo for 52months. In a post hoc analysis, we analyzed the
      association between metformin, MMA and a validated Neuropathy Score (NPS).
      RESULTS: Metformin vs placebo increased MMA at the end of the study (95%CI: 0.019
      to 0.055, p=0.001). Mediation analysis showed that the effect of metformin on the
      NPS consisted of a beneficial effect through lowering HbA1c (-0.020 per gram
      year) and an adverse effect through increasing MMA (0.042 per gram year),
      resulting in a non-significant net effect (0.032 per gram year, 95% CI: -0.121 to
      0.182, p=0.34). CONCLUSION: Metformin not only reduces serum levels of B12, but
      also progressively increases serum MMA. The increase of MMA in metformin users
      was associated with significant worsening of the NPS. These results provide
      further support that metformin-related B12 deficiency is clinically relevant.
      Monitoring of B12 in users of metformin should be considered.

PMID- 29174301
TI  - Dynamic changes in retinal vessel diameter during acute hyperglycemia in type 1
      diabetes.
AB  - AIMS: To investigate changes in retinal vessel diameter during acute
      hyperglycemia in patients with type 1 diabetes. METHODS: We conducted a study on
      11 subjects with type 1 diabetes. Euglycemia was maintained for 3h followed by
      induction of hyperglycemia and simultaneous bolus of rapid acting insulin. Two
      fundus photos were captured during euglycemia and five fundus photos, blood
      glucose and blood pressure were taken every 30min for 2.5h post-prandial. Central
      retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were
      measured over the study visit and examined using generalized linear mixed models.
      RESULTS: In a multivariate mixed model, mean CRAE and CRVE were reduced at 90min
      post-prandial in both zones B and C. In repeated measures analysis, arterioles
      exhibited a significant association with change in vessel caliber per change in
      blood glucose. Inconsistent effects of blood pressure on vessel diameter were
      also measured. CONCLUSIONS: We document a change in retinal vessel diameter
      during acute hyperglycemia in persons with type 1 diabetes. Larger controlled
      studies are required to further investigate this phenomenon and to more
      accurately assess if hyperglycemia has direct effects on retinal vessel diameter.

PMID- 29174302
TI  - The interaction of pulse width and current intensity on the extent of cortical
      plasticity evoked by vagus nerve stimulation.
AB  - BACKGROUND: Repeatedly pairing a tone with a brief burst of vagus nerve
      stimulation (VNS) results in a reorganization of primary auditory cortex (A1).
      The plasticity-enhancing and memory-enhancing effects of VNS follow an inverted-U
      response to stimulation intensity, in which moderate intensity currents yield
      greater effects than low or high intensity currents. It is not known how other
      stimulation parameters effect the plasticity-enhancing effects of VNS. OBJECTIVE:
      We sought to investigate the effect of pulse-width and intensity on VNS efficacy.
      Here, we used the extent of plasticity induced by VNS-tone pairing to assess VNS
      efficacy. METHODS: Rats were exposed to a 9 kHz tone paired to VNS with varying
      current intensities and pulse widths. Cortical plasticity was measured as changes
      in the percent of area of primary auditory cortex responding to a range of sounds
      in VNS-treated rats relative to naive rats. RESULTS: We find that a combination
      of low current intensity (200 MUA) and short pulse duration (100 MUs) is
      insufficient to drive cortical plasticity. Increasing the pulse duration to 500
      MUs results in a reorganization of receptive fields in A1 auditory cortex. The
      extent of plasticity engaged under these conditions is less than that driven by
      conditions previously reported to drive robust plasticity (800 MUA with 100 MUs
      wide pulses). CONCLUSION: These results suggest that the plasticity-enhancing and
      memory-enhancing effects of VNS follow an inverted-U response of stimulation
      current that is influenced by pulse width. Furthermore, shorter pulse widths may
      offer a clinical advantage when determining optimal stimulation current. These
      findings may facilitate determination of optimal VNS parameters for clinical
      application.

PMID- 29174303
TI  - Transcranial Direct Current Stimulation (tDCS) paired with a decision-making task
      reduces risk-taking in a clinically impulsive sample.
AB  - BACKGROUND: Impulsivity is a multidimensional personality trait observed across a
      variety of psychiatric disorders. Transcranial direct current stimulation (tDCS)
      applied over dorsolateral prefrontal cortex (DLPFC) has shown promise as an
      intervention to reduce impulsivity. OBJECTIVE: To investigate the effects of tDCS
      paired with a decision-making task on risk-taking in Veterans with a clinical
      history of impulsive behavior. METHODS: This was a randomized, single-blind, sham
      controlled study. Participants performed the Balloon Analogue Risk Task (BART)
      while concurrently receiving either active or sham tDCS (right anodal/left
      cathodal over DLPFC) twice a day for five days. To evaluate generalization, the
      Risk Task was performed before and after the complete course of intervention. To
      evaluate durability, the BART and Risk Task were administered again at one and
      two month follow-up sessions. RESULTS: Thirty Veterans participated: 15 received
      active tDCS and 15 received sham tDCS. For the trained BART task, individual
      growth curve analysis (IGC) examining individual variation of the growth rates
      over time showed no significant variations in individual trajectory changes over
      time (beta = 0.02, p > 0.05). For the untrained Risk Task, IGC showed that the
      active tDCS group had a significant 46% decrease in risky choice from pre-to post
      intervention, which persisted through the one and two month follow-up sessions.
      The sham tDCS group showed no significant change in risky choice from pre-to post
      intervention. CONCLUSIONS: tDCS over DLPFC paired with a decision-making task
      effectively reduced risk-taking behavior in a group of Veterans with clinically
      relevant impulsivity. Results suggest that this approach may be an effective
      neuroplasticity-based intervention for patients affected by impulsivity.

PMID- 29174304
TI  - Simultaneous rTMS and psychotherapy in major depressive disorder: Clinical
      outcomes and predictors from a large naturalistic study.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is considered an
      efficacious non-invasive neuromodulation treatment for major depressive disorder
      (MDD). However, little is known about the clinical outcome of combined rTMS and
      psychotherapy (rTMS + PT). Through common neurobiological brain mechanisms, rTMS
      + PT may exert enhanced antidepressant effects compared to the respective
      monotherapies. OBJECTIVE: The current naturalistic study aimed to evaluate
      feasibility and clinical outcome of rTMS + PT in a large group of MDD patients.
      The second aim was to identify clinical predictors of response and remission.
      METHODS: A total of 196 patients with MDD were treated with at least 10 sessions
      of simultaneous rTMS and PT. rTMS was applied over the DLPFC, either 10 Hz left
      or 1 Hz right. Psychotherapy was based on principles of cognitive behavioral
      therapy (CBT). Symptoms were measured using the BDI each fifth session until end
      of treatment and at 6-month follow-up. Comparisons were made between responders
      and non-responders, as well as between the 10 Hz and 1 Hz protocol. Additionally,
      baseline variables and early BDI change were evaluated as predictors of
      response/remission. MAJOR FINDINGS AND CONCLUSIONS: 1) Combining rTMS and PT
      resulted in a 66% response and a 56% remission rate at the end of treatment with
      60% sustained remission at follow-up. Compared to previous findings in RCTs,
      these rates are relatively high; 2) No differences were found between the 10 Hz
      and 1 Hz TMS regarding clinical outcome; 3) Clinical baseline variables were not
      predictive of treatment outcomes; 4) Early symptom improvement (at session 10)
      was highly predictive of response, and may therefore be used to guide rTMS + PT
      continuation; 5) Based on the current findings in a large naturalistic study,
      future studies employing a more standardized method are warranted to draw solid
      conclusions on the unique effect of rTMS + PT.

PMID- 29174305
TI  - Perinatal hypothyroidism increases play behaviors in juvenile rats.
AB  - Thyroid hormones play an instrumental role in the development of the central
      nervous system. During early development, the fetus is dependent on maternal
      thyroid hormone production due to the dysfunction of its own thyroid gland. Thus,
      maternal thyroid dysfunction has been shown to elicit significant abnormalities
      in neural development, neurochemistry, and behavior in offspring. Previous
      reports have suggested that human maternal hypothyroidism may increase the
      chances of having children with autism spectrum disorder and attention
      deficit/hyperactivity disorder. However, very few studies have evaluated social
      behaviors in animal models of perinatal hypothyroidism. To evaluate the
      possibility that hypothyroidism during development influences the expression one
      of the most commonly observed non-reproductive social behaviors, juvenile play,
      we used the validated rat model of perinatal hypothyroidism by methimazole
      administration (MMI; 0.025% in drinking water) from GD12-PD23. Control animals
      had regular drinking water. During adolescence (PD33-35), we tested subjects for
      juvenile play behavior by introducing them to a same-sex, unfamiliar (since
      weaning) littermate for 30min. Play behaviors and other behaviors (sleep, social
      contact, locomotion) were then scored. MMI-treated subjects played more than
      twice as much as control animals, and the increase in some behaviors was
      particularly dramatic in males. Locomotor and other affiliative social behaviors
      were unaffected. These data suggest that perinatal hypothyroidism may alter the
      organization of the neural networks regulating play behaviors, but not other
      social behaviors. Moreover, this implicates perinatal hypothyroidism as a
      potential etiological factor in the development of neurobehavioral disorders,
      particularly those characterized by heightened social interactions and
      impulsivity.

PMID- 29174307
TI  - Testing the effectiveness of cognitive interventions in alleviating accelerated
      long term forgetting (ALF).
AB  - It is well established that when retrieval or other forms of testing follow
      shortly after the acquisition of new information, long-term memory is improved in
      healthy subjects (Roediger & Karpicke, 2006). It is not known whether such early
      interventions would alleviate ALF, a condition in which early retention is
      normal, but there is a steep decline over longer intervals. A different
      behavioral intervention (i.e., an interposed recall of a story after a longer
      delay) was found to prevent subsequent memory loss in a single case with ALF
      (Jansari, Davis, McGibbon, Firminger, & Kapur, 2010; McGibbon & Jansari, 2013),
      but this has yet to be replicated. In the present study, we sought to test the
      effectiveness of early rehearsal as well as a later interposed recall on long
      term memory. Three men with ALF and 10 matched, healthy males (mean age = 67 yr;
      mean education = 15 yr) were compared for story recall following 3 early
      intervention conditions. There were two early rehearsal conditions: Repeated
      Recall (2 additional recalls were requested in the initial 30 min interval) and
      Repeated Recall With Discussion (2 additional recalls plus discussion occurred in
      the initial 30 min interval) as well as a Control condition, in which there was
      no additional rehearsal in the first 30 min. Memory for 6 stories (2 in each
      condition) was tested at 0 min, 30 min, 1 day, 1 week and 4 weeks. In addition,
      to evaluate the possible sustaining effect of an additional retrieval ("booster
      recall") between 1 wk and 4 wk delays, 1 story from each of the early
      intervention conditions was recalled at 2 weeks' delay. Consistent with the
      profile characteristic of ALF, nonparametric statistics revealed no group
      differences at 0 or 30 min recalls. For Control stories, the ALF group's recall
      was impaired by 24 h delay. For stories in either of the early rehearsal
      conditions, the patients showed better retention, performing within normal limits
      until the 4 week recall. The "booster recall" session at 2 weeks benefitted the
      patients' retention at 4 weeks, with patients' mean recall remaining within
      normal limits only for those stories recalled at 2 weeks. These results indicate
      that behavioral interventions including early rehearsal in the first several min
      and a booster recall at a much later time point help to prevent ALF. Confirmation
      of the usefulness of these interventions in other cases and investigating whether
      these cognitive techniques can be extended to "real world" applications are the
      logical next steps.

PMID- 29174308
TI  - Effectiveness of extended release naltrexone to reduce alcohol cravings and use
      behaviors during treatment and at follow-up.
AB  - Changes in cravings to drink alcohol and alcohol use behaviors were examined
      among 337 patients who were administered extended-release naltrexone (XR-NTX) in
      conjunction with psychosocial treatment in community-based substance use disorder
      treatment programs. Cravings and use behaviors were assessed at multiple time
      points (baseline; weeks 1, 2, and 3 after the first dose; monthly after the first
      four assessments; and at 30- and 60-days after the last dose). A total of 863
      doses (M=2.6, SD=1.8) were administered and the majority of patients (65%) took
      more than one dose. Alcohol craving scores decreased from 19 to 5.7 after the
      first dose of XR-NTX. Days of primary alcohol use at admission (M=10.5, SD=10.1)
      were reduced at discharge (M=to 1.2, SD=4.6). At the first follow-up, 79.8%
      reported no alcohol use and 77.8% reported no alcohol use at the second follow
      up. The expected side effects were reported but the medication was well tolerated
      and there was no relationship between side effects and subsequent dose.
      Unexamined or unaccounted for variables (e.g., motivation, external pressures to
      remain in treatment) are "real world" consequences that may have impacted the
      outcome of this study. Results indicated that use of the antagonist medication XR
      NTX may be related to significant decreases in alcohol craving and use while a
      patient is in treatment, as well as at 30- and 60-days after the final dose.

PMID- 29174306
TI  - Sex and gender differences in substance use disorders.
AB  - The gender gap in substance use disorders (SUDs), characterized by greater
      prevalence in men, is narrowing, highlighting the importance of understanding sex
      and gender differences in SUD etiology and maintenance. In this critical review,
      we provide an overview of sex/gender differences in the biology, epidemiology and
      treatment of SUDs. Biological sex differences are evident across an array of
      systems, including brain structure and function, endocrine function, and
      metabolic function. Gender (i.e., environmentally and socioculturally defined
      roles for men and women) also contributes to the initiation and course of
      substance use and SUDs. Adverse medical, psychiatric, and functional consequences
      associated with SUDs are often more severe in women. However, men and women do
      not substantively differ with respect to SUD treatment outcomes. Although several
      trends are beginning to emerge in the literature, findings on sex and gender
      differences in SUDs are complicated by the interacting contributions of
      biological and environmental factors. Future research is needed to further
      elucidate sex and gender differences, especially focusing on hormonal factors in
      SUD course and treatment outcomes; research translating findings between animal
      and human models; and gender differences in understudied populations, such as
      those with co-occurring psychiatric disorders and gender-specific populations,
      such as pregnant women.

PMID- 29174309
TI  - Lung cancer's real adjuvant EGFR targeted therapy questions.

PMID- 29174311
TI  - Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental
      traumatic brain injury by mitigating autophagy dysfunction and mitophagy
      activation.
AB  - Dynamin-related protein 1 (Drp1) is a key regulator of mitochondrial fission. Our
      previous studies proved that the inhibition of Drp1 may help attenuate traumatic
      brain injury (TBI)-induced functional outcome and cell death through maintaining
      normal mitochondrial morphology and inhibiting activation of apoptosis. However,
      the molecular mechanisms of Drp1 after TBI remain poorly understood. In this
      study, we investigated the role of mitochondrial division inhibitor 1 (Mdivi-1),
      a small molecule inhibitor of Drp1, in underlying mechanisms of general autophagy
      and mitochondria autophagy (mitophagy) after experimental TBI. In vivo, we found
      that autophagosomes accumulated in cortical neurons at 24h after TBI, owing to
      the enhanced autophagy indicated by the accumulation of LC3 and the decrease of
      p62; but Mdivi-1 reversed the enhancement. Mdivi-1 also alleviated the number of
      LC3 puncta and TUNEL-positive structures in cells, indicating that autophagy
      maybe involved in Mdivi-1's anti-apoptosis effects. Then, the expression level of
      mitochondrial dynamics related and mitophagy related proteins was assessed using
      the isolated mitochondria. The results showed that TBI-induced mitochondrial
      fission (represented by Drp1), mtDNA concentration down-regulation and PTEN
      induced putative kinase 1 (PINK1)-Parkin mediated mitophagy activation were all
      inhibited by Mdivi-1. In addition, TBI-induced blood-brain barrier (BBB)
      disruption and matrix metalloproteinases (MMP)-9 expression up-regulation were
      inhibited following Mdivi-1 treatment. In vitro, Mdivi-1 significantly alleviated
      the scratch injury-induced cell death, loss of mitochondrial membrane potential,
      reactive oxygen species (ROS) production and ATP reduction in primary cortical
      neurons (PCNs). Additionally, the lysosome inhibitor chloroquine (CQ) abrogated
      the Mdivi-1-induced decrease in autophagosomes accumulation and cell death at 24h
      both in the basal state and under the conditions of scratch cell injury.
      Together, these data demonstrate that Mdivi-1 mitigates TBI-induced BBB
      disruption and cell death at least in part by a mechanism involving inhibiting
      autophagy dysfunction and mitophagy activation.

PMID- 29174310
TI  - Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II
      IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label,
      phase 3 study.
AB  - BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for
      patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT
      and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected
      NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We
      aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus
      cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2)
      NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in
      China. We enrolled patients aged 18-75 years with completely resected (R0), stage
      II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC.
      Patients were stratified by N stage and EGFR mutation status and randomised (1:1)
      by Pocock and Simon minimisation with a random element to either gefitinib (250
      mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and
      8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles.
      The primary endpoint was disease-free survival in the intention-to-treat
      population, which comprised all randomised patients; the safety population
      included all randomised patients who received at least one dose of study
      medication. Enrolment to the study is closed but survival follow-up is ongoing.
      The study is registered with ClinicalTrials.gov, number NCT01405079. FINDINGS:
      Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222
      patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin.
      Median follow-up was 36.5 months (IQR 23.8-44.8). Median disease-free survival
      was significantly longer with gefitinib (28.7 months [95% CI 24.9-32.5]) than
      with vinorelbine plus cisplatin (18.0 months [13.6-22.3]; hazard ratio [HR] 0.60,
      95% CI 0.42-0.87; p=0.0054). In the safety population, the most commonly reported
      grade 3 or worse adverse events in the gefitinib group (n=106) were raised
      alanine aminotransferase and asparate aminotransferase (two [2%] patients with
      each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus
      cisplatin group (n=87), the most frequently reported grade 3 or worse adverse
      events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia
      (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events
      were reported for seven (7%) patients who received gefitinib and 20 (23%)
      patients who received vinorelbine plus cisplatin. No interstitial lung disease
      was noted with gefitinib. No deaths were treatment related. INTERPRETATION:
      Adjuvant gefitinib led to significantly longer disease-free survival compared
      with that for vinorelbine plus cisplatin in patients with completely resected
      stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free
      survival, reduced toxicity, and improved quality of life, adjuvant gefitinib
      could be a potential treatment option compared with adjuvant chemotherapy in
      these patients. However, the duration of benefit with gefitinib after 24 months
      might be limited and overall survival data are not yet mature. FUNDING: Guangdong
      Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health
      and Family Planning Commission of People's Republic of China; Guangzhou Science
      and Technology Bureau; AstraZeneca China.

PMID- 29174313
TI  - The effect of cool water pack preparation on vaccine vial temperatures in
      refrigerators.
AB  - Cool water packs are a useful alternative to ice packs for preventing
      unintentional freezing of vaccines during outreach in some situations. Current
      guidelines recommend the use of a separate refrigerator for cooling water packs
      from ambient temperatures to prevent possible heat degradation of adjacent
      vaccine vials. To investigate whether this additional equipment is necessary, we
      measured the temperatures that vaccine vials were exposed to when warm water
      packs were placed next to vials in a refrigerator. We then calculated the effect
      of repeated vial exposure to those temperatures on vaccine vial monitor status to
      estimate the impact to the vaccine. Vials were tested in a variety of
      configurations, varying the number and locations of vials and water packs in the
      refrigerator. The calculated average percentage life lost during a month of
      repeated warming ranged from 20.0% to 30.3% for a category 2 (least stable)
      vaccine vial monitor and from 3.8% to 6.0% for a category 7 (moderate stability)
      vaccine vial monitor, compared to 17.0% for category 2 vaccine vial monitors and
      3.1% for category 7 vaccine vial monitors at a constant 5  degrees C. The number
      of vials, number of water packs, and locations of each impacted vial warming and
      therefore percentage life lost, but the vaccine vial monitor category had a
      higher impact on the average percentage life lost than any of the other
      parameters. The results suggest that damage to vaccines from repeated warming
      over the course of a month is not certain and that cooling water packs in a
      refrigerator where vaccines are being stored may be a useful practice if safe
      procedures are established.

PMID- 29174312
TI  - Association of Corynebacterium pseudotuberculosis recombinant proteins rCP09720
      or rCP01850 with rPLD as immunogens in caseous lymphadenitis immunoprophylaxis.
AB  - Caseous lymphadenitis (CLA) is a chronic disease responsible for significant
      economic losses in sheep and goat breeding worldwide. The treatment for this
      disease is not effective, and an intense vaccination schedule would be the best
      control strategy. In this study, we evaluated the associations of rCP09720 or
      rCP01850 proteins from Corynebacterium pseudotuberculosis with recombinant
      exotoxin phospholipase D (rPLD) as subunit vaccines in mice. Four experimental
      groups (10 animals each) were immunized with a sterile 0.9% saline solution (G1),
      rPLD (G2), rPLD + rCP09720 (G3), and rPLD + rCP01850 (G4). The mice received two
      doses of each vaccine at a 21-day interval and were challenged 21 days after the
      last immunization. The animals were evaluated daily for 40 days after the
      challenge, and mortality rate was recorded. The total IgG production level
      increased significantly in the experimental groups on day 42 after the first
      vaccination. Similarly, higher levels of specific IgG2a were observed in
      experimental groups G2, G3, and G4 compared to the IgG1 levels on day 42. G4
      showed a significant (p < .05) humoral response against both antigens of the
      antigenic formulations. The cellular immune response induced by immunization was
      characterized by a significant (p < .05) production of interferon-gamma compared
      to that in the control, while the concentrations of interleukin (IL)-4 and IL-12
      were not significant in any group. A significant increase of tumor necrosis
      factor was observed only in G4. The survival rates after the challenge were 30%
      (rPLD), 40% (rPLD + rCP09720), and 50% (rPLD + rCP01850). Thus, the association
      of rCP01850 with rPLD resulted in the best protection against the challenge with
      C. pseudotuberculosis and induced a more intense type 1 T-helper cell immune
      response.

PMID- 29174314
TI  - Development of a broadly protective modified-live virus vaccine candidate against
      porcine reproductive and respiratory syndrome virus.
AB  - Modified-live virus (MLV) vaccines are widely used to protect pigs against
      porcine reproductive and respiratory syndrome virus (PRRSV). However, current MLV
      vaccines do not confer adequate levels of heterologous protection, presumably due
      to the substantial genetic diversity of PRRSV isolates circulating in the field.
      To overcome this genetic variation challenge, we recently generated a synthetic
      PRRSV strain containing a consensus genomic sequence of PRRSV-2. We demonstrated
      that our synthetic PRRSV strain confers unprecedented levels of heterologous
      protection. However, the synthetic PRRSV strain at passage 1 (hereafter
      designated CON-P1) is highly virulent and therefore, is not suitable to be used
      as a vaccine in pigs. In the present study, we attenuated CON-P1 by continuously
      passaging the virus in MARC-145 cells, a non-natural host cell line. Using a
      young pig model, we demonstrated that the synthetic virus at passages 90 and 122
      (designated as CON-P90 and CON-P122, respectively) were fully attenuated, as
      evidenced by the significantly reduced viral loads in serum and tissues and the
      absence of lung lesion in the infected pigs. Most importantly, CON-P90 confers
      similar levels of heterologous protection as its parental strain CON-P1. Taken
      together, the results indicate that CON-P90 is an excellent candidate for the
      formulation of next generation of PRRSV MLV vaccines with improved levels of
      heterologous protection.

PMID- 29174315
TI  - Workshop report: Nucleic acid delivery devices for HIV vaccines: Workshop
      proceedings, National Institute of Allergy and Infectious Diseases, Bethesda,
      Maryland, USA, May 21, 2015.
AB  - On May 21st, 2015, the U.S. National Institute of Allergy and Infectious Diseases
      (NIAID) convened a workshop on delivery devices for nucleic acid (NA) as vaccines
      in order to review the landscape of past and future technologies for
      administering NA (e.g., DNA, RNA, etc.) as antigen into target tissues of animal
      models and humans. Its focus was on current and future applications for
      preventing and treating human immunodeficiency virus (HIV) infection and acquired
      immune deficiency syndrome (AIDS) disease, among other infectious-disease
      priorities. Meeting participants presented the results and experience of
      representative clinical trials of NA vaccines using a variety of alternative
      delivery devices, as well as a broader group of methods studied in animal models
      and at bench top, to improve upon the performance and/or avoid the drawbacks of
      conventional needle-syringe (N-S) delivery. The subjects described and discussed
      included (1) delivery targeted into oral, cutaneous/intradermal, nasal, upper and
      lower respiratory, and intramuscular tissues; (2) devices and techniques for jet
      injection, solid, hollow, and dissolving microneedles, patches for topical
      passive diffusion or iontophoresis, electroporation, thermal microporation, nasal
      sprayers, aerosol upper-respiratory and pulmonary inhalation, stratum-corneum
      ablation by ultrasound, chemicals, and mechanical abrasion, and kinetic/ballistic
      delivery; (3) antigens, adjuvants, and carriers such as DNA, messenger RNA,
      synthesized plasmids, chemokines, wet and dry aerosols, and pollen-grain and
      microparticle vectors; and (4) the clinical experience and humoral, cellular, and
      cytokine immune responses observed for many of these target tissues,
      technologies, constructs, and carriers. This report summarizes the presentations
      and discussions from the workshop
      (https://web.archive.org/web/20160228112310/https://www.blsmeetings.net/NucleicAc
      dDeliveryDevices/), which was webcast live in its entirety and archived online
      (http://videocast.nih.gov/summary.asp?live=16059).

PMID- 29174316
TI  - A phase II randomized study to determine the safety and immunogenicity of the
      novel PIKA rabies vaccine containing the PIKA adjuvant using an accelerated
      regimen.
AB  - BACKGROUND: Human Rabies infection continues to be potentially fatal despite the
      availability of post-exposure prophylaxis with rabies vaccine. The PIKA Rabies
      vaccine adjuvant is a TLR3 agonist and has been shown to be safe and immunogenic
      in clinical phase I studies. METHODS: We conducted a phase II, open label,
      randomized study in healthy adults to assess the safety and immunogenicity of the
      PIKA rabies vaccine under an accelerated regimen. 126 subjects were randomized
      into two groups: control vaccine classic regimen ("control-classic") and PIKA
      vaccine accelerated regimen ("PIKA-accelerated"). Subjects were followed up for
      safety and rabies virus neutralizing antibodies (RVNA). RESULTS: Both the control
      and PIKA vaccines were generally well tolerated. 57.6% of subjects in the PIKA
      vaccine group, compared with 43.8% of subjects in the control-classic group,
      achieved the target RVNA titer of >=0.5 IU/mL by Day 7. All subjects achieved the
      target RVNA titer by Day 14. The RVNA geometric mean titer at Day 7 was 0.60
      IU/ml in the PIKA vaccine group and 0.39 IU/ml in the control-classic group. At
      Day 14, the RVNA geometric mean titer was 18.25 IU/ml in the PIKA-accelerated
      group and 19.24 IU/ml in the control-classic group. The median time taken to
      reach the target RVNA titer level of >=0.5 IU/mL was 7.0 days (95% CI: 7.0-42.0
      days) in the PIKA-accelerated group and 14.0 days (95% CI: 7.0-42.0 days) in the
      control-classic group. CONCLUSION: The accelerated regimen using the
      investigational PIKA Rabies vaccine was well-tolerated and demonstrated non
      inferior immunogenicity compared to the classic regimen using the commercially
      available vaccine in healthy adults. Clinical trial registry: The study was
      registered with clinicaltrials.gov (NCT02956421).

PMID- 29174317
TI  - Status and progress of hepatitis B control through vaccination in the South-East
      Asia Region, 1992-2015.
AB  - In 2016, the Immunization Technical Advisory Group of the South-East Asia Region
      (SEAR) endorsed a regional goal to achieve <=1% prevalence of hepatitis B surface
      antigen (HBsAg) among 5-year-old children by 2020. Chronic hepatitis B virus
      (HBV) infection is largely preventable with a birth dose of hepatitis B vaccine
      (HepB-BD) followed by two to three additional doses. We reviewed the progress
      towards hepatitis B control through vaccination in SEAR during 1992-2015. We
      summarized hepatitis B vaccination data and reviewed the literature to determine
      the prevalence of chronic HBV infection pre- and post-vaccine introduction. We
      used a mathematical model to determine post-vaccine prevalence of HBsAg among 5
      year olds in countries lacking national serosurvey data and estimated the impact
      of vaccination on disease burden. Regional coverage with three doses of hepatitis
      B vaccine (HepB3) increased from 56% in 2011 to 87% in 2015. By 2016, 7 of 11
      countries had introduced universal HepB-BD. Regional HepB-BD coverage increased
      from 9% in 2011 to 34% in 2015. In 2015, estimated HBsAg among 5 year olds was
      1.1% with variability among countries. Myanmar (3.8%), Timor-Leste (2.7%),
      Indonesia (1.8%), and India (1%) had the highest prevalence of HBsAg. During 1992
      2015, vaccination prevented approximately 16 million chronic HBV infections and
      2.6 million related deaths. In 2015, around 197,640 perinatal HBV infections
      occurred in SEAR with majority occurring in India (62%), Bangladesh (24%), and
      Myanmar (8%). Myanmar had the highest rate of perinatal chronic HBV infections at
      16 per 1000 live births. Despite significant progress in the control of HBV, SEAR
      needs to secure political commitment for elimination and consider additional
      strategies, such as promoting health facility births, universal birth dose
      administration, developing strong coordination between health sectors, and using
      alternative vaccine delivery methods, to improve HepB-BD coverage and
      subsequently achieve HBV control and elimination.

PMID- 29174318
TI  - Factors influencing on influenza vaccination and its trends of coverage in
      patients with diabetes in Korea: A population-based cross-sectional study.
AB  - BACKGROUND: Influenza infection is a contagious disease and annual influenza
      vaccination is recommended to the patients with chronic diseases. Although
      diabetes is an indication for influenza vaccination, the global rate of influenza
      vaccination is insufficient. Therefore, our study aimed to elucidate influenza
      vaccination statuses among patients with diabetes and the related factors in
      Korea. METHODS: A total of 32,268 subjects (4,540 with and 27,728 without
      diabetes) from the Korea National Health and Nutrition Examination Survey III-VI
      (2005-2015) were included. Socioeconomic factors and health-related factors were
      analyses for the relation of influenza vaccination by Student's t-test, the chi
      squared test and a multivariate logistic regression analysis. RESULTS: The
      influenza vaccination coverage rates were 50.0% in the diabetes mellitus (DM)
      group and 38.2% in the non-DM group. The trends in influenza vaccination rates
      during KNHANES III-VI were not significant in each group (P trend  =  0.24 in the
      DM group, 0.30 in the non-DM group). Socioeconomic (older age, female sex, higher
      family income, and medical aid insurance) and health-related factors (lack of
      risky alcohol consumption, obesity, and recent health check-ups) were associated
      with influenza vaccination among patients with DM. CONCLUSIONS: The rate of
      influenza vaccination among patients with diabetes is insufficient in Korea. More
      efforts are needed to increase the influenza vaccination rates among vulnerable
      at-risk populations.

PMID- 29174319
TI  - Different Dietary Patterns and New-Onset Diabetes Mellitus After Kidney
      Transplantation: A Cross-Sectional Study.
AB  - OBJECTIVE: To verify the association of dietary patterns and dietary components
      with new-onset diabetes mellitus after transplantation (NODAT). DESIGN: Cross
      sectional study. SUBJECTS: Adult kidney transplant recipients, without history of
      diabetes before transplantation, who received a kidney transplant and were
      followed up for at least 1 year. One hundred and sixteen subjects recruited
      between January 2013 and August 2014. Diagnosis of NODAT was established
      according to the American Diabetes Association criteria for type 2 diabetes.
      METHODS: Demographic, clinical, and anthropometric data were collected. Dietary
      intake was assessed by food frequency questionnaire, administered by a registered
      dietitian. Dietary patterns were identified by cluster analysis. Chi-square test
      was used to verify the association between dietary patterns and NODAT. Total
      energy, fiber, and cholesterol intake were calculated. Consumption of
      macronutrients, carbohydrates, proteins, and fats (total fats and saturated,
      monounsaturated, polyunsaturated and trans fatty acids), were expressed in
      percentage of total energy intake. RESULTS: Twenty-eight patients developed NODAT
      in the follow-up period. They presented higher body mass index and body fat
      percentage, as well as higher levels of triglycerides and urinary
      protein/creatinine ratio than the non-NODAT group. Two dietary patterns, I and
      II, were identified. Pattern II was characterized by higher intake of total,
      saturated, monounsaturated, and trans fats than pattern I. No association between
      the dietary patterns and NODAT was identified (P = .905), and there was no
      difference in the distribution of macronutrients, dietary fiber, and dietary
      cholesterol between the groups with and without NODAT. CONCLUSION: Posttransplant
      dietary patterns were not different between patients with and without NODAT.
      Further larger and prospective studies are needed to evaluate a possible
      relationship between dietary components and NODAT incidence in kidney transplant
      recipients.

PMID- 29174320
TI  - [Prerequisite for hematopoietic cellular therapy programs to set up chimeric
      antigen receptor T-cell therapy (CAR T-cells): Guidelines from the Francophone
      Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].
AB  - CAR T-cells are autologous or allogeneic human lymphocytes that are genetically
      engineered to express a chimeric antigen receptor targeting an antigen expressed
      on tumor cells such as CD19. CAR T-cells represent a new class of medicinal
      products, and belong to the broad category of Advanced Therapy Medicinal Products
      (ATMPs), as defined by EC Regulation 2007-1394. Specifically, they are
      categorized as gene therapy medicinal products. Although CAR T-cells are cellular
      therapies, the organization for manufacturing and delivery is far different from
      the one used to deliver hematopoietic cell grafts, for different reasons
      including their classification as medicinal products. Currently available
      clinical observations were mostly produced in the context of trials conducted
      either in the USA or in China. They demonstrate remarkable efficacy for patients
      presenting advanced or poor-prognosis hematological malignancies, however with
      severe side effects in a significant proportion of patients. Toxicities can and
      must be anticipated and dealt with in the context of a full coordination between
      the clinical cell therapy ward in charge of the patient, and the neighboring
      intensive care unit. The present workshop aimed at identifying prerequisites to
      be met in order for French hospitals to get efficiently organized and fulfill
      sponsors' expectations before initiation of clinical trials designed to
      investigate CAR T-cells.

PMID- 29174321
TI  - [Management of the chronic graft versus host disease: Guidelines from the
      Francophone society of bone marrow transplantation and cellular therapies (SFGM
      TC)].
AB  - The Francophone society of bone marrow transplantation and cellular therapy (SFGM
      TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical
      practices harmonization workshop series in September 2016 in Lille, France. The
      objective of our workshop is to discuss chronic graft versus host disease and to
      provide recommendations for the indications and treatment of this condition.

PMID- 29174322
TI  - Comparison of Patient Survival Between Hemodialysis and Peritoneal Dialysis Among
      Patients Eligible for Both Modalities.
AB  - BACKGROUND: Although peritoneal dialysis (PD) costs less to the health care
      system compared to in-center hemodialysis (HD), it is an underused therapy.
      Neither modality has been consistently shown to confer a clear benefit to patient
      survival. A key limitation of prior research is that study patients were not
      restricted to those eligible for both therapies. STUDY DESIGN: Retrospective
      cohort study. SETTING & PARTICIPANTS: All adult patients developing end-stage
      renal disease from January 2004 to December 2013 at any of 7 regional dialysis
      centers in Ontario, Canada, who had received at least 1 outpatient dialysis
      treatment and had completed a multidisciplinary modality assessment. PREDICTOR:
      HD or PD. OUTCOMES: Mortality from any cause. RESULTS: Among all incident
      patients with end-stage renal disease (1,579 HD and 453 PD), PD was associated
      with lower risk for death among patients younger than 65 years. However, after
      excluding approximately one-third of all incident patients deemed to be
      ineligible for PD, the modalities were associated with similar survival
      regardless of age. This finding was also observed in analyses that were
      restricted to patients initiating dialysis therapy electively as outpatients. The
      impact of modality on survival did not vary over time. LIMITATIONS: The
      determination of PD eligibility was based on the judgment of the
      multidisciplinary team at each dialysis center. CONCLUSIONS: HD and PD are
      associated with similar mortality among incident dialysis patients who are
      eligible for both modalities. The effect of modality on survival does not appear
      to change over time. Future comparisons of dialysis modality should be restricted
      to individuals who are deemed eligible for both modalities to reflect the
      outcomes of patients who have the opportunity to choose between HD and PD in
      clinical practice.

PMID- 29174324
TI  - When less is more: how many doses of PCV are enough?

PMID- 29174323
TI  - Pneumococcal conjugate vaccine 13 delivered as one primary and one booster dose
      (1 + 1) compared with two primary doses and a booster (2 + 1) in UK infants: a
      multicentre, parallel group randomised controlled trial.
AB  - BACKGROUND: Infants in the UK were first offered a pneumococcal conjugate vaccine
      (PCV7) in 2006, given at 2 and 4 months of age and a booster dose at 13 months (2
      + 1 schedule). A 13-valent vaccine (PCV13) replaced PCV7 in 2010. We aimed to
      compare the post-booster antibody response in UK infants given a reduced priming
      schedule of PCV13 (ie, a 1 + 1 schedule) versus the current 2 + 1 schedule and to
      assess the potential effect on population protection. METHODS: In this
      multicentre, parallel group, randomised controlled trial, we recuited infants due
      to receive their primary immunisations aged up to 13 weeks on first vaccinations
      by information booklets mailed out via the NHS Child Health Information Service
      and the UK National Health Application and Infrastructure Services. Eligible
      infants were randomly assigned (1:1) to receive PCV13 at 2, 4, and 12 months (2 +
      1 schedule) or 3 and 12 months of age (1 + 1 schedule) delivered with other
      routine vaccinations. Randomisation was done by computer-generated permuted block
      randomisation, with a block size of six. Participants and clinical trial staff
      were not masked to treatment allocation. The primary endpoint was serotype
      specific immunoglobulin G concentrations values (geometric mean concentrations
      [GMC] in MUg/mL) measured in blood samples collected at 13 months of age.
      Analysis was by modified intention to treat with all individuals included by
      randomised group if they had a laboratory result. This trial is registered on the
      EudraCT clinical trial database, number 2015-000817-32, and ClinicalTrials.gov,
      number NCT02482636. FINDINGS: Between September, 2015, and June, 2016, 376
      infants were assessed for eligibility. 81 infants were excluded for not meeting
      the inclusion criteria (n=50) or for other reasons (n=31). 213 eligible infants
      were enrolled and randomly allocated to group 1 (n=106; 2 + 1 schedule) or to
      group 2 (n=107; 1 + 1 schedule). In group 1, 91 serum samples were available for
      analysis 1 month after booster immunisation versus 86 in group 2. At month 13,
      post-booster, GMCs were equivalent between schedules for serotypes 3 (0.61 MUg/mL
      in group 1 vs 0.62 MUg/mL in group 2), 5 (1.74 MUg/mL vs 2.11 MUg/mL), 7F (3.98
      MUg/mL vs 3.36 MUg/mL), 9V (2.34 MUg/mL vs 2.50 MUg/mL), and 19A (8.38 MUg/mL vs
      8.83 MUg/mL). Infants given the 1 + 1 schedule had significantly greater
      immunogenicity post-booster than those given the 2 + 1 schedule for serotypes 1
      (8.92 MUg/mL vs 3.07 MUg/mL), 4 (3.43 MUg/mL vs 2.55 MUg/mL), 14 (16.9 MUg/mL vs
      10.49 MUg/mL), and 19F (14.76 MUg/mL vs 11.12 MUg/mL; adjusted p value range
      <0.001 to 0.047). The 2 + 1 schedule was superior for serotypes 6A, 6B, 18C and
      23F (adjusted p value range <0.0001 to 0.017). In a predefined numerical subset
      of all of the infants recruited to the study (n=40 [20%]), functional serotype
      specific antibody was similar between schedules. 26 serious adverse events were
      recorded in 21 (10%) infants across the study period; 18 (n=13) were in the 2 + 1
      group and eight (n=8) in the 1 + 1 group. Only one serious adverse event, a high
      temperature and refusal to feed after the first vaccination visit in a child on
      the 2+1 schedule was considered related to vaccine. INTERPRETATION: Our findings
      show that for nine of the 13 serotypes in PCV13, post-booster responses in
      infants primed with a single dose are equivalent or superior to those seen
      following the standard UK 2 + 1 schedule. Introducing a 1 + 1 schedule in
      countries with a mature PCV programme and established herd immunity is likely to
      maintain population control of vaccine-type pneumococcal disease. FUNDING: NIHR
      and the Bill & Melinda Gates Foundation.

PMID- 29174325
TI  - Corrections.

PMID- 29174326
TI  - Goodbye to the SIRS, the reason why we do not need you.

PMID- 29174327
TI  - Cardiac arrest associated with aortic valve regurgitation.
AB  - Blunt chest trauma can cause not only damage to the thoracic cage, but can also
      injure intracardiac structures including the papillary muscles, chordae
      tendineae, and valve leaflets. Aortic valve (AV) injury secondary to blunt chest
      trauma is a rare occurrence. Clinically, AV injury may be missed during the
      initial post-trauma assessment due to the lack of suspicion of cardiac
      involvement. Thus, the diagnosis of AV injury is often delayed or missed for a
      time interval of days to months. As a consequence, the traumatic AV regurgitation
      can rapidly or progressively lead to congestive heart failure unless surgically
      corrected. Therefore, emergency physicians should be aware of the possibility of
      intracardiac structure injury, such as valvular injuries, after blunt chest
      trauma. Guidelines for the appropriate use of bedside cardiac ultrasound (BCU)
      recommend BCU should be performed in all patients with new murmurs for clinically
      significant valvular lesions that could potentially change management. We
      described the case of a 73-year-old female patient with AV injury after blunt
      trauma. She experienced cardiac arrest (CA) secondary to a moderate-to-severe
      traumatic AR, which was successfully treated with emergency AV replacement. We
      discuss how to diagnose and manage a CA patient, aided by BCU, with ventricular
      failure associated with persistent AV regurgitation. To the best of our
      knowledge, this is the first case report on CA associated with isolated rupture
      of bicuspid AV rupture and AV regurgitation secondary to blunt chest trauma
      because of the lack of early suspicion of AV injury.

PMID- 29174328
TI  - Variation in hospital admission rates between a tertiary care and two
      freestanding emergency departments.
AB  - BACKGROUND: Recently, freestanding emergency departments (FSEDs) have grown
      significantly in number. Critics have expressed concern that FSEDs may increase
      healthcare costs. OBJECTIVE: We determined whether admission rates for identical
      diagnoses varied among the same group of physicians according to clinical
      setting. METHODS: This was a retrospective comparison of adult admission rates
      (n=3230) for chest pain, chronic obstructive pulmonary disease (COPD), asthma,
      and congestive heart failure (CHF) between a hospital-based ED (HBED) and two
      FSEDs throughout 2015. Frequency distribution and proportions were reported for
      categorical variables stratified by facility type. For categories with cell
      frequency less or equal to 5, Fisher's Exact test was used to calculate a P
      value. Chi square tests were used to assess difference in proportions of
      potential predictor variables between the HBED and FSEDs. For continuous
      variables, the mean was reported and Student's t-test assessed the difference in
      means between HBED and FSED patients. Multivariate logistic regression analyses
      were performed to estimate the unadjusted and adjusted prevalence odds ratio with
      95% confidence interval (CI) for patient disposition outcomes associated with
      type of ED facility visited. RESULTS: Of 3230 patients, 53% used the HBED and 47%
      used the FSED. Patients visiting the HBED and FSED varied significantly in
      gender, acuity levels, diagnosis, and number of visits. Age was not significantly
      different between facilities. Multivariable adjusted estimated prevalence odds
      ratio for patients admitted were 1.2 [95%CI: 1.0-1.4] in the HBED facility
      compared to patients using FSEDs. CONCLUSION: In our healthcare system, FSEDs
      showed a trend towards a 20% lower admission rate for chest pain, COPD, asthma
      and CHF.

PMID- 29174329
TI  - Initial inferior vena cava diameter predicts massive transfusion requirements in
      blunt trauma patients: A retrospective cohort study.
AB  - OBJECTIVES: The inferior vena cava (IVC) diameter is associated with shock and
      increased mortality in trauma patients. However, there are no reports examining
      the association between the IVC diameter and massive transfusion (MT)
      requirements in trauma patients. The aim of this study was to evaluate the
      association between IVC diameter and MT requirements in patients with blunt
      trauma. METHODS: We retrospectively reviewed all patients who were consecutively
      hospitalized with blunt trauma (Injury Severity Score [ISS] >=16) between from
      November 1, 2011 to March 30, 2016. Univariate and multivariate analyzes were
      performed to identify the independent predictors of MT (defined as >10units of
      red cell concentrate transfusions within 24h of admission). Receiver operating
      characteristic curve and the area under the curve (AUC) were estimated. RESULTS:
      Of the 222 patients included in this study, MT occurred in 22.5% patients. On
      multiple regression analysis, IVC diameter [Odds ratio (OR), 0.88; 95% confidence
      interval (CI), 0.80-0.96; p<0.01], fibrin degradation product (FDP; OR, 1.01; 95%
      CI, 1.00-1.01; p<0.01), and fibrinogen level (OR, 0.99; 95% CI, 0.98-1.00;
      p<0.01) were strong predictors of MT. IVC diameter demonstrated moderate accuracy
      (AUC, 0.74; cutoff level, 13.0mm; sensitivity, 67%; specificity, 73%). Combined
      cutoff levels of FDP <80.5MUg/ml, fibrinogen >=165mg/dl, and IVC diameter >=13mm
      could also determine how unnecessary a MT was with 100% accuracy. CONCLUSIONS:
      Initial IVC diameter is a predictor of MT in blunt trauma patients.

PMID- 29174330
TI  - Association between commercial vehicle driver at-fault crashes involving
      sleepiness/fatigue and proximity to rest areas and truck stops.
AB  - INTRODUCTION: There is ongoing concern at the national level about the
      availability of adequate commercial vehicle rest areas and truck stops for
      commercial vehicle drivers to rest or to wait for a delivery window. METHODS: A
      retrospective case-control study was conducted to determine the association
      between the occurrence of sleepiness/fatigue-related (cases) vs. all other human
      factor-related commercial vehicle driver at-fault crashes (controls) and
      proximity to rest areas, weigh stations with rest havens, and truck stops.
      RESULTS: Commercial vehicle driver at-fault crashes involving sleepiness/fatigue
      were more likely to occur on roadways where the nearest rest areas/weigh stations
      with rest havens/truck stops were located 20 miles or more from the commercial
      vehicle crash site (Odds Ratio [OR]=2.32; Confidence Interval [CI] 1.615, 3.335]
      for 20-39.9 miles vs. <20 miles; and OR=6.788 [CI 2.112, 21.812] for 40+ miles)
      compared to commercial vehicle at-fault driver crashes with human factors other
      than sleepiness/fatigue cited in crash reports. Commercial vehicle driver at
      fault crashes involving sleepiness/fatigue also were more likely to occur on
      parkways compared to interstates (adjusted OR=3.747 [CI 2.83, 4.95]), during
      nighttime hours (adjusted OR=6.199 [CI 4.733, 8.119]), and on dry pavement
      (adjusted OR 1.909, [CI 1.373, 2.655]). CONCLUSIONS: The use of statewide crash
      data analysis coupled with ArcGIS mapping capabilities provided the opportunity
      to both statistically determine and to visualize the association between rest
      area/weigh station with rest haven/truck stop distance and the occurrence of
      commercial vehicle driver at-fault crashes involving sleepiness/fatigue.
      Implementation and evaluation of commercial vehicle employer policies and
      interventions such as the use of commercial vehicle driver fatigue alert systems
      may help to reduce fatigue and sleepiness in commercial vehicle drivers. These
      results can be used by state and local highway transportation officials to inform
      and increase truck parking availability, especially on parkways.

PMID- 29174331
TI  - Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription
      Factor-Mediated Cellular Reprogramming.
AB  - Reprogramming of cellular identity using exogenous expression of transcription
      factors (TFs) is a powerful and exciting tool for tissue engineering, disease
      modeling, and regenerative medicine. However, generation of desired cell types
      using this approach is often plagued by inefficiency, slow conversion, and an
      inability to produce mature functional cells. Here, we show that expression of
      constitutively active SMAD2/3 significantly improves the efficiency of induced
      pluripotent stem cell (iPSC) generation by the Yamanaka factors. Mechanistically,
      SMAD3 interacts with reprogramming factors and co-activators and co-occupies OCT4
      target loci during reprogramming. Unexpectedly, active SMAD2/3 also markedly
      enhances three other TF-mediated direct reprogramming conversions, from B cells
      to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons,
      highlighting broad and general roles for SMAD2/3 as cell-reprogramming
      potentiators. Our results suggest that co-expression of active SMAD2/3 could
      enhance multiple types of TF-based cell identity conversion and therefore be a
      powerful tool for cellular engineering.

PMID- 29174332
TI  - Injury Induces Endogenous Reprogramming and Dedifferentiation of Neuronal
      Progenitors to Multipotency.
AB  - Adult neurogenesis in the olfactory epithelium is often depicted as a
      unidirectional pathway during homeostasis and repair. We challenge the
      unidirectionality of this model by showing that epithelial injury unlocks the
      potential for Ascl1+ progenitors and Neurog1+ specified neuronal precursors to
      dedifferentiate into multipotent stem/progenitor cells that contribute
      significantly to tissue regeneration in the murine olfactory epithelium (OE). We
      characterize these dedifferentiating cells using several lineage-tracing strains
      and single-cell mRNA-seq, and we show that Sox2 is required for initiating
      dedifferentiation and that inhibition of Ezh2 promotes multipotent progenitor
      expansion. These results suggest that the apparent hierarchy of neuronal
      differentiation is not irreversible and that lineage commitment can be overridden
      following severe tissue injury. We elucidate a previously unappreciated pathway
      for endogenous tissue repair by a highly regenerative neuroepithelium and
      introduce a system to study the mechanisms underlying plasticity in the OE that
      can be adapted for other tissues.

PMID- 29174334
TI  - Is there a common vulnerability in cannabis phenomenology and schizotypy? The
      role of the N170 ERP.
AB  - Cannabis use is a known risk factor for the development of psychosis, although
      the precise nature of this relationship is unclear. The phenomenological
      experiences associated with cannabis use vary dramatically, and for some resemble
      certain features of psychosis. We hypothesized that individuals who report
      particularly unusual experiences associated with cannabis use would demonstrate
      similar electrophysiological patterns to those who score high on schizotypal
      personality traits. The Cannabis Experiences Questionnaire (CEQ) and the
      Schizotypal Personality Questionnaire (SPQ) were used to measure these
      experiences and traits. A sample of 97 individuals were placed into one of three
      experimental or two control groups based on their questionnaire scores. These
      were the "High CEQ", "High SPQ", "High on Both", "Average Users" and "Control"
      (non-using) groups. Participants completed a visual face perception task.
      Electroencephalography was used to measure the neural response to the stimuli.
      The N170 event-related potential (ERP) was used to measure perceptual encoding of
      the stimulus. The experimental groups elicited significantly reduced N170 ERPs
      compared to the Control group. The Average User group did not significantly
      differ from the Control group, and approached significance with the High SPQ
      group. None of the high scoring groups significantly differed in N170 ERP
      response from each other. Replicating past research, the CEQ and SPQ scales
      moderately correlated with each other. The attenuated N170 ERP demonstrated by
      the high scoring experimental groups may reflect a manifestation of an underlying
      shared vulnerability.

PMID- 29174333
TI  - Injury Activates Transient Olfactory Stem Cell States with Diverse Lineage
      Capacities.
AB  - Tissue homeostasis and regeneration are mediated by programs of adult stem cell
      renewal and differentiation. However, the mechanisms that regulate stem cell
      fates under such widely varying conditions are not fully understood. Using single
      cell techniques, we assessed the transcriptional changes associated with stem
      cell self-renewal and differentiation and followed the maturation of stem cell
      derived clones using sparse lineage tracing in the regenerating mouse olfactory
      epithelium. Following injury, quiescent olfactory stem cells rapidly shift to
      activated, transient states unique to regeneration and tailored to meet the
      demands of injury-induced repair, including barrier formation and proliferation.
      Multiple cell fates, including renewed stem cells and committed differentiating
      progenitors, are specified during this early window of activation. We further
      show that Sox2 is essential for cells to transition from the activated to
      neuronal progenitor states. Our study highlights strategies for stem cell
      mediated regeneration that may be conserved in other adult stem cell niches.

PMID- 29174335
TI  - Identification of genes carrying rare variants of moderate to large effect in
      schizophrenia: A replication study.

PMID- 29174336
TI  - Relationship between objectively measured sedentary behavior and health outcomes
      in schizophrenia patients: The PsychiActive project.
AB  - This study aimed to investigate possible relationships between sedentary behavior
      and body mass index (BMI), cardiorespiratory fitness (CRF), and health-related
      quality of life (HRQoL) in schizophrenia patients. Variables contributing to the
      variability in sedentary behavior were identified. Eighty-two schizophrenia
      outpatients (mean age+/-SD: 41.0+/-8.7years, 87% men, mean illness duration+/-SD:
      17.1+/-8.9years) wore a multisensor armband for 7 consecutive full days to
      objectively measure sedentary behavior. BMI, walking capacity (6-minute walking
      test) as a proxy for CRF estimation and HRQoL (Short Form 36-Item Health Survey
      questionnaire version 2) were also assessed. Correlation (Pearson or Spearman
      coefficients) and multiple regression analysis were used. Sedentary behavior was
      significantly associated with BMI, CRF, and the physical component summary score
      of HRQoL (r values, -0.34-0.41; all P<0.001) and remained significant after
      adjustments for age, illness duration, symptom severity, adherence to
      Mediterranean diet, smoking, and antipsychotic medication (all P<0.05). BMI, CRF
      and vitality were identified as determinants of sedentary behavior. Consistent
      relationships between sedentary behavior and BMI, CRF, and the physical component
      summary score of HRQoL were found in schizophrenia patients. All the identified
      determinants of sedentary behavior are modifiable and may be important areas for
      future interventions in this population.

PMID- 29174338
TI  - Authors' Reply.

PMID- 29174337
TI  - Arterial Thickness and Stiffness Are Independently Associated with Left
      Ventricular Strain.
AB  - BACKGROUND: The aim of this study was to examine the association between
      myocardial strain and arterial thickness and stiffness in young adults. Increased
      common carotid artery intima media thickness and peripheral arterial stiffness
      are known to precede coronary artery disease and cardiovascular (CV) events such
      as myocardial infarction and congestive heart failure. However, subclinical
      cardiac dysfunction can be detected in high-risk adults by myocardial strain
      echocardiography. The authors hypothesized that increased carotid artery intima
      media thickness would be associated with abnormal myocardial strain in young
      subjects who had obesity and type 2 diabetes mellitus. METHODS: CV risk factors
      were collected in 338 young adults participating in a prospective, cross
      sectional study. The CV parameters collected included intima-media thickness,
      peripheral arterial stiffness by brachial distensibility, and myocardial strain
      and strain rate. General linear models were constructed to determine if vascular
      structure and function measures were independently associated with myocardial
      strain and strain rate. RESULTS: A linear relationship was found between global
      longitudinal strain obtained from the four-chamber view and global strain rate in
      systole and carotid intima-media thickness (four-chamber global longitudinal
      strain: beta = 3.0, CV risk factor-adjusted R2 = 0.34; global strain rate in
      systole: beta = 0.0053, R2 = 0.21; P <= .0001) and between four-chamber global
      longitudinal strain and lower brachial distensibility (beta = -0.42, R2 = 0.22; P
      < .001). CONCLUSIONS: Adverse changes in vascular structure and function are
      simultaneously present with reduced myocardial systolic function.

PMID- 29174339
TI  - Feasibility of Left Ventricular Global Longitudinal Strain Measurements from
      Contrast-Enhanced Echocardiographic Images.
AB  - BACKGROUND: Although left ventricular global longitudinal strain (GLS) is an
      index of systolic function recommended by the guidelines, poor image quality may
      hamper strain measurements. While contrast agents are commonly used to improve
      endocardial visualization, no commercial speckle-tracking software is able to
      measure strain in contrast-enhanced images. This study aimed to test the accuracy
      of speckle-tracking software when applied to contrast-enhanced images in patients
      with suboptimal image quality. METHODS: We studied patients with a wide range of
      GLS values who underwent transthoracic echocardiography. Protocol 1 included 44
      patients whose images justified use of contrast but still allowed noncontrast
      speckle-tracking echocardiography (STE), which was judged as accurate and used as
      a reference. Protocol 2 included 20 patients with poor image quality that
      precluded noncontrast STE; cardiac magnetic resonance- (CMR-) derived strain was
      used as the reference instead. Half the manufacturer recommended dose of a
      commercial contrast agent (Definity/Optison/Lumason) was used to provide partial
      contrast enhancement. Higher than normal mechanical indices (0.6-0.7) and lowest
      frequency range for maximal penetration settings were used for imaging. GLS was
      measured (Epsilon) with and without contrast-enhanced images and by CMR-derived
      feature tracking (TomTec). Comparisons included linear regression and Bland
      Altman analyses. RESULTS: The contrast STE analysis failed in 4/64 patients (6%).
      Manual corrections were needed to optimize tracking with contrast in all
      patients. GLS measurements were in good agreement between contrast and
      noncontrast images (r = 0.85; mean GLS in the contrast images, -12.9% +/- 4.7%;
      bias, 0.34% +/- 2.4%). Good agreement was also noted between contrast STE- and
      CMR-derived strain (r = 0.83; mean, GLS -13.5% +/- 4.0%; bias, 0.72% +/- 2.5%).
      CONCLUSIONS: We found that GLS measurements from contrast-enhanced images are
      feasible and accurate in most patients, even in those with poor image quality
      that precludes strain measurements without contrast enhancement.

PMID- 29174340
TI  - Echocardiographic Estimation of Mean Pulmonary Artery Pressure: A Comparison of
      Different Approaches to Assign the Likelihood of Pulmonary Hypertension.
AB  - BACKGROUND: Current guidelines advise using echocardiography for noninvasive
      estimation of the likelihood that a patient has pulmonary hypertension (PH). To
      estimate the echocardiographic probability of PH, the maximal tricuspid
      regurgitation velocity (TR Vmax) is recommended as the main parameter to use over
      more complex algorithms that provide an estimation of pulmonary artery pressure.
      This preference is based on concerns about inaccuracies and amplification of
      measurement errors that can occur from using derived variables. However, this has
      not been examined systematically. METHODS: A retrospective database analysis was
      performed of invasively determined measurements of right heart pressure in 90
      patients, corresponding echocardiographic estimations of pulmonary artery
      pressure, and additional parameters obtained within 24 hours. Several algorithms
      were compared for their correlations and accuracy parameters. RESULTS: Although a
      Bland-Altman analysis demonstrated that all examined algorithms exhibited
      inaccuracies that could be clinically relevant in individuals, algorithms
      estimating mean pulmonary artery pressure (PAPm) on the basis of tricuspid
      regurgitation generally exhibited stronger correlations with invasively
      determined PAPm and more accurate identification of PH than did TR Vmax.
      Echocardiographic estimation of right atrial pressure >15 mm Hg exhibited the
      highest odds ratio for invasively confirmed PH, suggesting that this parameter is
      of additional diagnostic value. Indeed, algorithms that also considered right
      atrial pressure performed best, whereas empirical algorithms, TR Vmax, and
      methods relying on pulmonary acceleration time exhibited weaker performance.
      CONCLUSIONS: Although all methods are associated with inaccuracies,
      echocardiographically determined PAPm was superior to the current guideline
      recommendation of using TR Vmax with regard to its correlation with invasively
      determined PAPm and the presence of PH. PAPm may be considered as an alternative
      to TR Vmax for evaluating the echocardiographic probability of PH.

PMID- 29174341
TI  - Feasibility, Accuracy, and Reproducibility of Aortic Annular and Root Sizing for
      Transcatheter Aortic Valve Replacement Using Novel Automated Three-Dimensional
      Echocardiographic Software: Comparison with Multi-Detector Row Computed
      Tomography.
AB  - BACKGROUND: In transcatheter aortic valve replacement (TAVR), multi-detector row
      computed tomography (MDCT) is currently the standard imaging modality for correct
      prosthesis sizing, despite risks of radiation and contrast-induced renal injury.
      Three-dimensional (3D) transesophageal echocardiography (TEE) has been proposed
      as a potential alternative imaging technique, and recently, automated 3D
      transesophageal echocardiographic software (Aortic Valve Navigator [AVN], an
      unreleased prototype from Philips) has been developed for assessment of the
      aortic annulus and root. The aim of this study was to assess the feasibility,
      accuracy, and reproducibility of AVN measurements in TAVR candidates by
      performing a comparison with MDCT. METHODS: In 150 patients with severe,
      symptomatic aortic stenosis referred for TAVR, data on aortic annular and root
      dimensions prospectively acquired using 3D TEE and MDCT were retrospectively
      analyzed. Image quality on 3D TEE and the duration of analysis with AVN were
      recorded, as well as the aortic valve Agatston score on MDCT. RESULTS: Data were
      obtained using 3D TEE and MDCT in 100% of patients for aortic annular dimensions
      and in 89% for aortic root dimensions. The mean duration of analysis using AVN
      was 4.2 +/- 1.0 min, but it was significantly shorter with better 3D
      echocardiographic image quality and lower Agatston score on MDCT. Correlation of
      measurements between 3D TEE and MDCT was good to excellent for all anatomic
      locations (sinotubular junction mean diameter, R = 0.71; sinus of Valsalva mean
      diameter, R = 0.87; aortic annular mean diameter, R = 0.75; aortic annular
      perimeter, R = 0.83; aortic annular area, R = 0.91), with low inter- and
      intraobserver variability (intraclass correlation coefficient >= 0.93 and r >=
      0.90 for all locations). Comparison based on conventional prosthesis sizing
      charts yielded excellent agreement in prosthesis size choice (kappa = 0.90).
      CONCLUSIONS: New automated 3D transesophageal echocardiographic software allows
      accurate modeling and reproducible quantification of aortic annular and root
      dimensions with high feasibility. An excellent correlation between measurements
      with AVN and MDCT and agreement in prosthesis sizing suggests the use of AVN in
      clinical practice as potential alternative to MDCT before TAVR.

PMID- 29174342
TI  - Serum fetuin-A levels in obese and non-obese subjects with and without type 2
      diabetes mellitus.
AB  - BACKGROUND: Higher fetuin-A expression is linked to both obesity and type 2
      diabetes mellitus (T2DM), However, studies in non-obese patients with T2DM are
      scarce. METHODS: 345 newly diagnosed T2DM patients and 300 subjects with normal
      glucose tolerance (NGT) were divided into obese and non-obese subgroups,
      respectively. Serum fetuin-A and adiponectin levels and related parameters were
      measured. RESULTS: T2DM patients with obesity had higher fetuin-A levels compared
      with non-obese patients and obese NGT subjects (p<0.001). Significant
      correlations were observed between fetuin-A and most metabolic parameters in
      obese NGT and T2DM subjects, but which was not in non-obese patients with T2DM.
      The independent associations were found between fetuin-A and free fatty acids,
      HOMA-IR, C-reactive protein and adiponectin only in obese NGT and T2DM subjects
      (all p<0.05). The adjusted odds ratios for obesity were increased with increasing
      quartile of fetuin-A in both T2DM and NGT subjects in logistic regression models
      (p for trend<0.001), but which was more significant in T2DM patients. CONCLUSION:
      Higher serum fetuin-A levels in obese T2DM patients compared with non-obese
      patients and obese NGT subjects supports the hypothesis that fetuin-A may be as a
      bridge connecting obesity and obesity-related T2DM.

PMID- 29174343
TI  - Tim-3 expression predicts the abnormal innate immune status and poor prognosis of
      glioma patients.
AB  - Malignant glioma, the most common and devastating primary brain tumor, has
      serious effects on human health with high risk of recurrence and short survival
      periods. Recently, the exploitation of immunological mechanisms shed new lights
      for developing novel therapeutic strategies for glioma pathogenesis. Tim-3, a
      member of T cell immunoglobulin and mucin domain family, has been involved in
      multiple diseases, including tumor, by regulating the viability and function of
      immunocytes. In the present study, we detected Tim-3 expression on peripheral
      innate immunocytes from glioma patients and analyzed their correlation with
      clinical indices. We found that the number of CD3-CD56+ NK cells decreased in
      glioma patients. Compared with healthy controls, glioma patients had higher Tim-3
      expression on peripheral CD3-CD56+ NK cells and CD14+ monocytes. Tim-3+ NK cells
      had decreased capability of IFN-r secretion, while Tim-3+ monocytes showed a M2
      like phenotype. Importantly, Tim-3 level on both NK cells and monocytes
      positively correlated with the ratio of Ki-67+ tumor cells. Moreover, patients
      with high percentage of Tim-3+ monocytes showed high risk of recurrence or death.
      Our present work gives new insights into the innate immune mechanisms in glioma
      and might provide new evidences for the clinical practice of Tim-3-based
      immunotherapy in glioma.

PMID- 29174344
TI  - The role of plasma lipoprotein lipase, hepatic lipase and GPIHBP1 in the
      metabolism of remnant lipoproteins and small dense LDL in patients with coronary
      artery disease.
AB  - BACKGROUND: The relationship between plasma lipoprotein lipase (LPL), hepatic
      triglyceride lipase (HTGL), glycosylphosphatidylinositol anchored HDL binding
      protein1 (GPIHBP1) concentration and the metabolism of remnant lipoproteins (RLP)
      and small dense LDL (sdLDL) in patients with coronary artery disease (CAD) is not
      fully elucidated. METHODS: One hundred patients who underwent coronary
      angiography were enrolled. The plasma LPL, HTGL and GPIHBP1 concentrations were
      determined by ELISA. The time dependent changes in those lipases, lipids and
      lipoproteins were studied at a time-point just before, and 15min, 4h and 24h
      after heparin administration. RESULTS: The LPL concentration exhibited a
      significant positive correlation with HDL-C, and inversely correlated with TG and
      RLP-C. The HTGL concentration was positively correlated with RLP-C and sdLDL-C.
      The HTGL ratio of the pre-heparin/post-heparin plasma concentration and sdLDL
      C/LDL-C ratio were significantly greater in CAD patients than in non-CAD
      patients. GPIHBP1 was positively correlated with LPL and inversely correlated
      with RLP-C and sdLDL-C. CONCLUSION: The HTGL concentration was positively
      correlated with RLP-C and sdLDL-C, while LPL and GPIHBP1 were inversely
      correlated with RLP-C and sdLDL-C. These results suggest that elevated HTGL is
      associated with increased CAD risk, while elevated LPL is associated with a
      reduction of CAD risk.

PMID- 29174346
TI  - Self-reported adverse food reactions and anaphylaxis in the SchoolNuts study: A
      population-based study of adolescents.
AB  - BACKGROUND: Adolescents are at the highest risk of death from anaphylaxis, yet
      few population-based studies have described the frequencies and risk factors for
      allergic reactions caused by accidental allergen ingestion in this group.
      METHODS: We describe the prevalence, frequency, and associated risk factors for
      recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia,
      recruited from a stratified, random, population-based sample of schools
      (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse
      reaction details, including anaphylaxis, were identified by using a student
      questionnaire over the past year. RESULTS: Of 547 students with possible IgE
      mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to
      a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93
      anaphylaxis episodes. Peanut and tree nuts were the most common food triggers.
      Among students with current IgE-mediated food allergy, those with resolved or
      current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI,
      1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1])
      were at greatest risk of any adverse food reaction, and those with nut allergy
      were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or
      current asthma was not associated with increased risk of severe reactions (aOR,
      0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7]). CONCLUSIONS: Adolescents with
      food allergy are frequently exposed to food allergens. Those with asthma and more
      than 2 food allergies were at the greatest risk for adverse food reactions. Those
      with nut allergies were most at risk of severe reactions.

PMID- 29174345
TI  - Effective exercise intervention period for improving body function or activity in
      patients with knee osteoarthritis undergoing total knee arthroplasty: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Various systematic reviews and/or meta-analyses examining the effects
      of pre- or postoperative exercise on body function or activity in patients
      undergoing total knee arthroplasty (TKA) have been published. However, the
      interventional period needed to at least improve outcomes is unknown. OBJECTIVE:
      The aim of this systematic review and meta-analysis was to investigate the
      exercise intervention period needed to effectively improve body function or
      activity before and after TKA in patients with knee osteoarthritis (OA). METHODS:
      Studies published until July 2017 were included in the review. The Grading of
      Recommendations Assessment, Development, and Evaluation (GRADE) approach was
      applied to each meta-analysis to determine the quality of the evidence. RESULTS:
      Twenty-seven randomized controlled trials were identified. A meta-analysis
      indicated that exercises performed for 8 weeks after discharge in addition to
      standard postoperative intervention effectively improved body function as
      assessed using pain level; physical function, and stiffness on the Western
      Ontario and McMaster Universities Arthritis Index; extension strength; active
      knee flexion range of motion; timed up and go test; and gait speed. CONCLUSION:
      Overall, we found low- to moderate-quality evidence that an 8-week exercise
      period was needed after discharge to improve body function and activity in
      patients with knee OA undergoing TKA.

PMID- 29174349
TI  - A Meta-Analysis of HIV Postexposure Prophylaxis Among Sexually Assaulted Patients
      in the United States.
AB  - Sexual assault (SA) is a major public health problem that leaves patients at risk
      for HIV. The gold standard of medical treatment for SA patients includes
      prophylactic treatment to prevent HIV. A meta-analysis was conducted and examined
      the rates of nonoccupational postexposure prophylaxis (n-PEP) offered to,
      accepted, and completed by SA patients who presented to emergency departments in
      the United States. Four points of data were analyzed: (a) SA patients who met the
      criteria and were offered n-PEP, (b) SA patients who were offered n-PEP and
      accepted the medication, (c) SA patients who accepted n-PEP treatment and
      completed at least one follow-up appointment, and (d) SA patients who completed
      the entire course of n-PEP. Results of the meta-analysis indicated that
      approximately half of the patients who were offered n-PEP accepted the
      medication. However, only 25.7% of SA patients who accepted n-PEP completed the
      full course.

PMID- 29174348
TI  - Addressing Prevention Among HIV-Uninfected Women in PMTCT Programs in South
      India.
AB  - With nearly one million HIV-infected women in India, prevention of mother-to
      child transmission (PMTCT) programs serve an important role. While PMTCT programs
      focus on mothers living with HIV infection, offering them to uninfected pregnant
      women may prevent maternal HIV infections. To inform future efforts to offer
      PMTCT programs to uninfected women, we conducted focus groups with 24 uninfected
      women in the South Indian state of Karnataka who had given birth within the
      previous 2 years to explore their perceptions and experiences about HIV education
      and screening during pregnancy. Although all the participants had undergone HIV
      testing at a public health facility during pregnancy, they reported little
      knowledge about HIV transmission or prevention. Revisions are needed in existing
      PMTCT program curricula and instruction methods before they can be offered to
      uninfected women as an HIV prevention strategy.

PMID- 29174347
TI  - Discovery of 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425), a
      potent and orally bioavailable tissue-nonspecific alkaline phosphatase (TNAP)
      inhibitor.
AB  - Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme crucial for bone
      matrix mineralization via its ability to hydrolyze extracellular inorganic
      pyrophosphate (ePPi), a potent mineralization inhibitor, to phosphate (Pi). By
      the controlled hydrolysis of ePPi, TNAP maintains the correct ratio of Pi to ePPi
      and therefore enables normal skeletal and dental calcification. In other areas of
      the body low ePPi levels lead to the development of pathological soft-tissue
      calcification, which can progress to a number of disorders. TNAP inhibitors have
      been shown to prevent these processes via an increase of ePPi. Herein we describe
      the use of a whole blood assay to optimize a previously described series of TNAP
      inhibitors resulting in 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide
      (SBI-425), a potent, selective and oral bioavailable compound that robustly
      inhibits TNAP in vivo.

PMID- 29174350
TI  - Predicting Pediatric Patients Who Require Care at a Trauma Center: Analysis of
      Injuries and Other Factors.
AB  - BACKGROUND: Triage decision correctness for children in motor vehicle crashes can
      be affected by occult injuries. There is a need to develop a transfer score (TS)
      metric for children that can help quantify the likelihood that an injury is
      present that would require transfer to a trauma center (TC) from a non-TC, and
      improve triage decision making. Ultimately, the TS metric might be useful in an
      advanced automatic crash notification algorithm, which uses vehicle telemetry
      data to predict the risk of serious injury after a motor vehicle crash using an
      approach that includes metrics to describe injury severity, time sensitivity, and
      predictability. STUDY DESIGN: Transfer score metrics were calculated in 4
      pediatric age groups (0 to 4, 5 to 9, 10 to 14, 15 to 18 years) for the most
      frequent motor vehicle crash injuries using the proportions of children
      transferred to a TC or managed at a non-TC using the National Inpatient Sample
      years 1998 to 2007. To account for the maximum Abbreviated Injury Scale (MAIS)
      injury, a co-injury adjusted transfer score (TSMAIS) was calculated. The TS and
      TSMAIS range from 0 to 1, with 1 indicating highly transferred injuries. RESULTS:
      Injuries in younger patients were more likely to be transferred (median TS 0.48,
      0.35, 0.25, and 0.23 for 0 to 4, 5 to 9, 10 to 14, and 15 to 18 years,
      respectively). Injuries more likely to be transferred in younger children
      occurred in the thorax and abdomen. Regardless of age, spine (median TSMAIS
      0.59), head (median TSMAIS 0.48), and thorax (median TSMAIS 0.46) injuries had
      the highest frequency for transfer. CONCLUSIONS: The TS metrics quantitatively
      describe age-specific transfer practices for children with particular injuries.
      This information can be useful in advanced automatic crash notification systems
      to alert first responders to the possibility of occult injuries and reduce
      undertriage of commonly missed injuries.

PMID- 29174351
TI  - Suicide by intravenous kerosene: A case report in Bangladesh.

PMID- 29174352
TI  - Influence of oxygen on the biosynthesis of polyunsaturated fatty acids in
      microalgae.
AB  - As one of the most important environmental factors, oxygen is particularly
      important for synthesis of n-3 polyunsaturated fatty acids (n-3 PUFA) in
      microalgae. In general, a higher oxygen supply is beneficial for cell growth but
      obstructs PUFA synthesis. The generation of reactive oxygen species (ROS) under
      aerobic conditions, which leads to the peroxidation of lipids and especially
      PUFA, is an inevitable aspect of life, but is often ignored in fermentation
      processes. Irritability, microalgal cells are able to activate a number of anti
      oxidative defenses, and the lipid profile of many species is reported to be
      altered under oxidative stress. In this review, the effects of oxygen on the PUFA
      synthesis, sources of oxidative damage, and anti-oxidative defense systems of
      microalgae were summarized and discussed. Moreover, this review summarizes the
      published reports on microalgal biotechnology involving direct/indirect oxygen
      regulation and new bioreactor designs that enable the improved production of
      PUFA.

PMID- 29174353
TI  - A new enrichment diagnostic platform for semen culture.
AB  - Urogenital bacterial infections have been described in literature as a potential
      cause of infertility. For the consequences that a failure in diagnosis could have
      on the evolution of male urogenital infectious disease, an accurate
      microbiological procedure to investigate the bacterial species composition of
      seminal fluid plays a crucial role to better understand the eventual correlation
      with infertility. In order to improve the quality of semen culture
      investigations, we have developed a new enrichment diagnostic platform. Semen
      samples of 540 infertile men were simultaneously analyzed using the standard
      microbiological semen culture method and an alternative new experimental
      technique (Brain Heart Infusion broth, BHI, enrichment). Our results established
      the possibility to apply BHI enrichment to detect bacteria from semen samples
      with higher sensitivity (100%) and negative predictive value (100%) than the
      standard technique.

PMID- 29174354
TI  - Purification and characterization of novel bi-functional GH3 family beta
      xylosidase/beta-glucosidase from Aspergillus niger ADH-11.
AB  - beta-Xylosidase plays an important role in xylan degradation by relieving the end
      product inhibition of endo-xylanase caused by xylo-oligosaccharides. beta
      Xylosidase has a wide range of applications in food, feed, paper and pulp,
      pharmaceutical industries and in bioconversion of lignocellulosic biomass. Hence,
      in the present study focused on purification, biochemical characterization and
      partial sequencing of purified beta-xylosidase from xylanolytic strain
      Aspergillus niger ADH-11. Acetone precipitation followed by GPC using Sephacryl S
      200 yielded 20.59-fold purified beta-xylosidase with 58.30% recovery. SDS-PAGE
      analysis of purified beta-xylosidase relieved a monomeric subunit with a
      molecular weight 120.48kDa. Kinetic parameters of purified beta-xylosidase viz
      Km, Vmax, Kcat and catalytic efficiency were assessed. Purified beta-xylosidase
      was additionally active on p-nitrophenyl-beta-d-glucopyranoside substrate also.
      Moreover, peptide mass fingerprinting analysis support our biochemical studies
      and showed that the purified protein is a novel beta-xylosidase with beta
      glucosidase activity and belongs to the bi-functional GH3 superfamily. Besides,
      tolerance of purified beta-xylosidase towards glucose and xylose was also
      assessed.

PMID- 29174355
TI  - A novel inhibition based biosensor using urease nanoconjugate entrapped
      biocomposite membrane for potentiometric glyphosate detection.
AB  - A potentiometric biosensor based on agarose-guar gum (A-G) entrapped bio
      nanoconjugate of urease with gold nanoparticles (AUNps), has been reported for
      the first time for glyphosate detection. The biosensor is based on inhibition of
      urease activity by glyphosate, which was measured by direct potentiometry using
      ammonium ion selective electrode covered with A-G-urease nanoconjugate membrane.
      TEM and FTIR analysis revealed nanoconjugate formation and its immobilization in
      A-G matrix respectively. The composite biopolymer employed for immobilization
      yields thin, transparent, flexible membrane having superior mechanical strength
      and stability. It retains the maximum activity (92%) of urease with negligible
      leaching. The conjugation of urease with AUNps allows improvement in response
      characteristics for potentiometric measurement. The biosensor shows a linear
      response in the glyphosate concentration range from 0.5ppm-50ppm, with limit of
      detection at 0.5ppm, which covers maximum residual limit set by WHO for drinking
      water. The inhibition of catalytic activity of urease nanoconjugate by gyphosate
      was confirmed by FTIR analysis. The response of fabricated biosensor is selective
      towards glyphosate as against various other pesticides. The biosensor exhibits
      good performance in terms of reproducibility and prolonged storage stability of
      180days. Thus, the present biosensor provides an alternative method for simple,
      selective and cost effective detection of glyphosate based on urease inhibition.

PMID- 29174356
TI  - Separation, purification, structures and anticoagulant activities of fucosylated
      chondroitin sulfates from Holothuria scabra.
AB  - In this study, a new fucosylated chondroitin sulfate (HsG) with an average
      molecular weight of 69.1 kDa was isolated from sea cucumber Holothuria scabra. We
      investigated the structure of the HsG by adopting monosaccharide composition
      analysis, disaccharide composition analysis, IR,1H and13C NMR spectra and
      methylation analysis. According to methylation results of desulfated/carboxyl
      reduced polysaccharides and the analysis of unsaturated disaccharides generated
      through the enzymolysis of the defucosed polysaccharides, it is shown that each
      branch is formed by one fucopyranosyl residue, wherein 55.7% of the fucopyranosyl
      residues are linked to the O-6 position of the N-acetylgalactosamine moiety,
      21.2% of the fucopyranosyl residues are linked to the O-3 position of beta-d
      glucuronic acid, 13.0% of the fucopyranosyl residues are linked to the O-4
      positions of the N-acetylgalactosamine moiety, and 10.1% of the fucopyranosyl
      residues are not linked to sulfate groups on the backbone. The backbone 
      >4)GlcUAbeta(1 -> 3)GalNAcbeta(1-> and sulfated fucose branches were composed of
      the beta-d-glucuronic acid, N-acetyl-beta-d- galactosamine, alpha-l-fucose and
      sulfate groups by the molar ratio of 1:1.72:2.34:3.29. The anticoagulant
      activities of the HsG was evaluated and compared with heparin. The result showed
      that the HsG could prolong the activated partial thromboplastin time.

PMID- 29174357
TI  - A novel detergent additive: Organic solvent- and thermo-alkaline-stable
      recombinant subtilisin.
AB  - In the present work, subtilisin gene from Bacillus subtilis PTTC 1023 was
      synthesized, cloned into the vector pD441-NH and expressed in E. coli BL21 (DE3).
      Recombinant subtilisin was purified in a single-step procedure by affinity
      chromatography. The molecular mass of the purified protein was determined to be
      about 40kDa by SDS-PAGE. The optimum pH and temperature values of its proteolytic
      activity were 10.5 and 50 degrees C, respectively and retained more than 70% and
      89% of its activity in pH range of 7-12 and 30-60 degrees C, respectively. Enzyme
      purity was estimated to be about 200- fold greater than that of the crude extract
      and subtilisin had a specific activity of 56.16U/mg, with a yield of about 87.9%.
      It was completely inhibited by phenylmethanesulfonyl fluoride, which strongly
      suggests its belonging to serine protease family. Interestingly, subtilisin
      protease displayed a significant compatibility with commercial detergents, and
      tolerance organic solvents, metallic ions and surfactants. The findings obtained
      demonstrated that protease of B. subtilis could potentially be used in future
      applications as an additive in detergent formulations.

PMID- 29174358
TI  - Structure analysis of a heteropolysaccharide from fruits of Lycium barbarum L.
      and anti-angiogenic activity of its sulfated derivative.
AB  - Angiogenesis plays a crucial role in tumor growth and development. Blocking
      angiogenesis of tumor cells has become one of the most promising approaches in
      cancer therapy. Here, an acidic polysaccharide designated LBP1B-S-2 with an
      average molecular weight of 80.00kDa, was extracted and purified from dried
      mature fruits of Lycium barbarum L. by DEAE SepharoseTM Fast Flow and Sephacryl S
      300 HR columns. Monosaccharide composition analysis indicated that the LBP1B-S-2
      was composed of rhamnose, arabinose, galactose and glucuronic acid in a molar
      ratio of 3.13: 53.55: 39.37: 3.95. The backbone of LBP1B-S-2 was consisted of 1,
      3-linked beta-d-Galp, 1, 6-linked beta-d-Galp and branches contained 1, 4-linked
      beta-d-GlcpA, T-linked beta-d-Galp, 1, 6-linked beta-d-Galp, T-linked alpha-l
      Araf, T-linked beta-l-Araf, 1, 5-linked alpha-l-Araf and T-linked beta-l-Rhap
      directly or indirectly attached to C-3 position of 1, 6-linked beta-d-Galp or C-6
      position of 1, 3-linked beta-d-Galp, according to the results of partial acid
      hydrolysis analysis, methylation analysis, IR and NMR spectra. The sulfated
      derivative of LBP1B-S-2, could significantly inhibit the tube formation of human
      microvascular endothelial cells (HMEC-1) in vitro at concentration of (95nM)
      without significant cytotoxicity.

PMID- 29174360
TI  - Impact of ionic liquid type on the structure, morphology and properties of silk
      cellulose biocomposite materials.
AB  - Microcrystalline cellulose and Bombyx mori silk blended biocomposite films were
      regenerated using various imidazolium-based ionic liquids. The films were
      characterized to understand the effect of the inter- and intra-molecular
      interactions upon the morphology and thermal properties. Various techniques were
      implemented to investigate structural, morphological and thermal properties of
      the biocomposite films, including Fourier transform infrared spectroscopy (FTIR),
      scanning electron microscope (SEM), thermal gravimetric analysis (TGA),
      differential scanning calorimetry (DSC) and X-ray scattering. Results show that
      the type of ionic liquid has strong influence on the structure of silk-cellulose
      composites that can form either amorphous or semicrystalline structures. While
      the thermal properties are independent of the type of cation in ionic liquids,
      the levels of beta-sheet configuration are dependent on the type of anion, which
      further causes changes on the biocomposite thermal properties. The topological
      image provided information to support morphological effects on the varying ionic
      liquids and X-ray scattering allowed for insight on the role of ionic liquids on
      the crystallinity and the spacing differences in biocomposite films. The results
      have demonstrated that there is a direct relationship between the intermolecular
      interactions in films and the anion structure of the ionic liquids.

PMID- 29174359
TI  - Expression of catalytically efficient xylanases from thermophilic fungus
      Malbranchea cinnamomea for synergistically enhancing hydrolysis of
      lignocellulosics.
AB  - In this study, two xylanase genes (GH10 and GH11) derived from Malbranchea
      cinnamomea, designated as XYN10A_MALCI and XYN11A_MALCI, respectively, were
      expressed in Pichia pastoris X33. The maximum level of xylanase expression was
      found to be 24.3U/ml for rXYN10A_MALCI and 573.32U/ml for rXYN11A_MALCI. The
      purified recombinant rXYN11A_MALCI was stable at 70 degrees C and catalytically
      active against a variety of substituted (arabinoxylans) as well as unsubstituted
      xylans. The hydrolytic potential of recombinant xylanases for enhancing the
      hydrolysis of acid/alkali pretreated lignocellulosics (rice straw and bagasse) by
      the commercial cellulase Cellic CTec2 was assessed which revealed that both
      rXYN10A_MALCI and rXYN11A_MALCI act synergistically with commercial cellulases
      and resulted in 1.54 and 1.58 folds improved hydrolysis of acid treated rice
      straw and alkali treated rice straw using cocktail comprising of Cellic CTec2 and
      XYN11A_MALCI (8:2 ratio) when compared to Cellic CTec2 alone at same protein
      loading rate of (~5.7mg/g biomass).

PMID- 29174362
TI  - Rupture of sinus of Valsalva aneurysm: Two case reports and a concise review of
      the literature.
AB  - BACKGROUND: The rupture of sinus of Valsalva aneurysm (RSoVA) is a rare disorder
      that affects the integrity of the cardiovascular system, disrupting its dynamics
      and resulting in a variety of manifestations. In this report, we discuss two
      cases of RSoVA that we encountered and review similar cases reported in the
      literature. METHODS: literature review of reported cases of RSoVA in PubMed and
      Google Scholar. RESULTS: A total of 223 cases were found and the final analysis
      included 225 cases, of which 69% occurred in males and the mean age was 38.9
      years. Dyspnea was the most common presenting symptom and 76% of the cases
      described continuous murmur on examination. The right sinus was affected in 61%
      of the cases and the fistula connected to the right chambers of the heart 73% of
      the time. CONCLUSION: RSoVA is a rare condition that is difficult to diagnose, it
      should be considered in the right context, particularly in young patients with
      symptoms of heart failure and the presence of continuous murmur on cardiac
      examination.

PMID- 29174363
TI  - Prognostic significance of late gadolinium enhancement on cardiac magnetic
      resonance in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Late gadolinium enhancement (LGE) on cardiac MRI indicates the
      myocardial fibrosis in hypertrophic cardiomyopathy (HCM), and the prognostic
      value of LGE in HCM has been described in several studies, but controversy exists
      given the limited power of these studies to predict future adverse cardiac
      events. The objective of this study was to perform a meta-analysis to
      systematically evaluate the predictive value of LGE on cardiac magnetic resonance
      (CMR) for future adverse cardiac events. METHODS: We systematically searched
      multiple database including PubMed, EMBASE, and Cochrane Library for cohort
      studies of the effects of LGE on clinical outcomes (sudden cardiac death
      (SCD)/aborted SCD, all cardiac death, and all-cause mortality) in patients with
      HCM. We performed a meta-analysis to determine pooled odds ratios (OR), weighted
      average annualized event rates, and summary receiver-operating characteristic
      (SROC) curves for these clinical events. RESULTS: We identified nine clinical
      studies, examining 1734 patients with LGE and 2036 without LGE, and an average
      follow-up of 2.9 years. The weighted average annualized event rates of
      SCD/aborted SCD in patients with HCM (positive LGE versus negative LGE) was 1.28%
      versus 0.32% (p < 0.001), and the pooled OR was 3.40 (95% CI: 1.90, 6.08; p <
      0.001). The sensitivity and specificity of predicting future cardiac events were
      0.83 (95% CI: 0.66, 0.93) and 0.45 (95% CI: 0.31, 0.59), respectively. The 5-year
      risk of SCD/aborted SCD was 6.4% in patients with LGE. The all cardiac death and
      all-cause mortality were also significantly increased in patients with LGE.
      However, the extent of LGE was not significantly related to the risk of
      SCD/aborted SCD. CONCLUSIONS: LGE is significantly associated with SCD/aborted
      SCD risk, all cardiac death and all-cause mortality in patients with HCM.
      Implantable cardioverter defibrillators (ICD) can be considered for those
      patients with LGE.

PMID- 29174361
TI  - Glycol chitosan assisted in situ reduction of gold on polymeric template for anti
      cancer theranostics.
AB  - Multifunctional biodegradable nanomaterials that could be used for both imaging
      and therapy are being researched extensively. A simple technique to synthesize
      multifunctional nanoparticles without compromising on any of their functionality
      is a challenge. We have attempted to optimize a two-step procedure of gold coated
      polymeric template involving 1) Single pot synthesis of PLGA nanoparticles with
      cationic surface charge using glycol chitosan and 2) in situ gold coating for
      formation of gold coated PLGA nanoshell (AuPLGA-NS). These gold-coated PLGA
      nanoparticles were explored for photothermal therapy (PTT) and as X-ray/CT
      contrast agents. Biocompatibility and photothermal cytotoxicity of AuPLGA-NS were
      evaluated in-vitro and results confirmed the therapeutic efficacy of these
      particles resulting in 80% cancer cell death. Besides, it also showed potential X
      ray/CT imaging ability with contrast equivalent to that of Iodine. The results
      demonstrated that these gold-coated PLGA nanoparticles synthesized by a simple
      approach could be used as a multifunctional nanosystem for cancer theranostics.

PMID- 29174364
TI  - Identification and characterization of interchangeable cross-species functional
      promoters between Babesia gibsoni and Babesia bovis.
AB  - The development of transgenic techniques has been reported in many protozoan
      parasites over the past few years. We recently established a successful transient
      transfection system for Babesia gibsoni based on Bg 5'-ef-1alpha promoter. This
      study investigated 6 homologous and 6 heterologous promoters for B. gibsoni and
      B. bovis and identified novel interchangeable cross-species functional promoters
      between B. gibsoni and B. bovis. Ten out of twelve promoters had heterologous
      promoter function. In particular, Bg 5'-ef-1alpha and Bg 5'-actin heterologous
      promoters resulted in a significantly higher luciferase activity than Bb 5'-ef
      1alpha homologous promoter in B. bovis. The present study showed that Bg 5'-actin
      promoted the highest luciferase activity in both B. gibsoni and B. bovis. The
      study further indicates that heterologous promoter function widely exists between
      B. gibsoni and B. bovis. This finding is an important step for future stable
      transfection construct design and for the production of vaccines based on
      transfected B. gibsoni and B. bovis parasites.

PMID- 29174365
TI  - Rickettsia diversity in southern Africa: A small mammal perspective.
AB  - Worldwide, including Africa, rickettsioses are recognized as emerging or re
      emerging infections. To date, little is known about the diversity of Rickettsia
      species that are naturally associated with small mammals in southern Africa. The
      aim of the study was to screen a diversity of small mammals for the presence of
      rickettsial DNA. Animals were trapped at 38 localities in South Africa and
      Namibia. In total, 1616 ear-tissue samples from 23 species representing 17 genera
      were tested using real-time (rt)PCR and multi-locus sequence typing (MLST). Of
      the 1616 samples 251 (15.5%) were positive in an initial rtPCR. In 16 of the 23
      investigated animal species rickettsial DNA was detected with an average
      prevalence of 15.7%. We herein describe for the first time four Rickettsia (R.)
      species known to be pathogenic for humans in rodents from South Africa, R.
      conorii, R. massiliae, R. felis and R. helvetica. In addition, by MLST and
      subsequent phylogenetic analyses so far undescribed Rickettsia species,
      Candidatus Rickettsia africaustralis, Candidatus Rickettsia rhabdomydis, and
      Candidatus Rickettsia muridii were confirmed. Further four new genotypes,
      genotype Rickettsia hofmannii, genotype Rickettsia stutterheimensis, genotype
      Rickettsia hogsbackensis and genotype Rickettsia kaalplaasensis, respectively,
      are described. The data indicate a surprisingly high diversity of Rickettsia in
      small mammals in South Africa and might indicate their possible role as
      reservoirs for Rickettsia. Ecological questions concerning their natural hosts
      such as small mammals, but also the role of livestock or pet animals, require
      further investigation. Particularly, data on the relevance of these rickettsiae
      for diseases in humans are of further interest.

PMID- 29174366
TI  - DNAJC12 deficiency: A new strategy in the diagnosis of hyperphenylalaninemias.
AB  - Patients with hyperphenylalaninemia (HPA) are detected through newborn screening
      for phenylketonuria (PKU). HPA is known to be caused by deficiencies of the
      enzyme phenylalanine hydroxylase (PAH) or its cofactor tetrahydrobiopterin (BH4).
      Current guidelines for the differential diagnosis of HPA would, however, miss a
      recently described DNAJC12 deficiency. The co-chaperone DNAJC12 is, together with
      the 70kDa heat shock protein (HSP70), responsible for the proper folding of PAH.
      All DNAJC12-deficient patients investigated to date responded to a challenge with
      BH4 by lowering their blood phenylalanine levels. In addition, the patients
      presented with low levels of biogenic amine in CSF and responded to
      supplementation with BH4, L-dopa/carbidopa and 5-hydroxytryptophan. The
      phenotypic spectrum ranged from mild autistic features or hyperactivity to severe
      intellectual disability, dystonia and parkinsonism. Late diagnosis result in
      permanent neurological disability, while early diagnosed and treated patients
      develop normally. Molecular diagnostics for DNAJC12 variants are thus mandatory
      in all patients in which deficiencies of PAH and BH4 are genetically excluded.

PMID- 29174367
TI  - Exercising with blocked muscle glycogenolysis: Adaptation in the McArdle mouse.
AB  - BACKGROUND: McArdle disease (glycogen storage disease type V) is an inborn error
      of skeletal muscle metabolism, which affects glycogen phosphorylase
      (myophosphorylase) activity leading to an inability to break down glycogen.
      Patients with McArdle disease are exercise intolerant, as muscle glycogen-derived
      glucose is unavailable during exercise. Metabolic adaptation to blocked muscle
      glycogenolysis occurs at rest in the McArdle mouse model, but only in highly
      glycolytic muscle. However, it is unknown what compensatory metabolic adaptations
      occur during exercise in McArdle disease. METHODS: In this study, 8-week old
      McArdle and wild-type mice were exercised on a treadmill until exhausted.
      Dissected muscles were compared with non-exercised, age-matched McArdle and wild
      type mice for histology and activation and expression of proteins involved in
      glucose uptake and glycogenolysis. RESULTS: Investigation of expression and
      activation of proteins involved in glycolytic flux revealed that in glycolytic,
      but not oxidative muscle from exercised McArdle mice, the glycolytic flux had
      changed compared to that in wild-type mice. Specifically, exercise triggered in
      glycolytic muscle a differentiated activation of insulin receptor, 5' adenosine
      monophosphate-activated protein kinase, Akt and hexokinase II expression, while
      inhibiting glycogen synthase, suggesting that the need and adapted ability to
      take up blood glucose and use it for metabolism or glycogen storage is different
      among the investigated muscles. CONCLUSION: The main finding of the study is that
      McArdle mouse muscles appear to adapt to the energy crisis by increasing
      expression and activation of proteins involved in blood glucose metabolism in
      response to exercise in the same directional way across the investigated muscles.

PMID- 29174368
TI  - An Integrative Review of Interventions to Support Parents When Managing Their
      Child's Pain at Home.
AB  - To identify interventions aimed at helping parents manage their child's pain at
      home and to establish which aspects of interventions were effective. Integrative
      narrative review. MEDLINE, CINAHL Plus, PsychINFO, PsychArticles, AMED, PubMed,
      Scopus and Web of Knowledge databases were searched in 2016. This narrative
      synthesis followed Centre for Reviews and Dissemination and Economic and Social
      Research Council guidance. Reasons attributed to intervention success were
      analyzed using content analysis. From 2,534 papers, 17 were included. A majority
      were randomized controlled trials (n = 13) and most addressed postoperative pain
      (n = 15). A range of interventions were found that directly targeted parents,
      including child-parent interactions and health care professional-parent
      interactions, as well as complex interventions. Three studies were successful in
      reducing child pain at home and seven in increasing appropriate analgesic drug
      administration. Analysis of reasons attributed to interventions success revealed
      characteristics of interventions, components of parental pain management, and key
      features of research that aid researchers in designing and evaluating
      interventions. Risk of bias was present because of inadequate randomization, lack
      of a control group, and underpowered studies. Nurses should be aware that
      targeting parents directly is the most effective way of reducing child pain at
      home. Nurses need to advocate for effective analgesics for their child patients
      because the ineffectiveness of many interventions was attributed to inadequate
      analgesic drugs. Once this is achieved, success in increasing analgesic drug
      administration is most likely reached via parent-targeted interventions and those
      targeting health care professional-parent interactions. Successful interventions
      will be tailored to the child and adequately powered. Including a measure of
      sedation will ensure sedation is not mistaken for analgesic effectiveness.
      Interventions should address multiple facets of pain management and include a
      measure of pain over a period as opposed to a snapshot in time.

PMID- 29174369
TI  - Analyzing the Genetic Spectrum of Vascular Anomalies with Overgrowth via Cancer
      Genomics.
AB  - Vascular anomalies are variably associated with overgrowth, skeletal anomalies,
      and abnormalities of the brain, leptomeninges, and eye. We assembled a 16
      institution network to determine the range of genetic variants associated with a
      spectrum of vascular anomalies with overgrowth, ranging from mild to severe.
      Because of the overlap between cancer-associated variants and previously
      described somatic variants in vascular overgrowth syndromes, we employed tumor
      genetic profiling via high-depth next-generation sequencing using a panel to
      assay affected tissue from a diverse cohort of subjects with vascular anomalies
      with overgrowth. Seventy-five percent (43/57) harbored pathogenic or likely
      pathogenic variants in 10 genes. We identified two genes (mTOR, PIK3R1) and
      several variants previously described in the setting of cancer but that, to our
      knowledge, have not been described in vascular malformations. All were identified
      at low variant allele frequency consistent with somatic mosaic etiology. By
      leveraging somatic variant detection technology typically applied to cancer in a
      cohort inclusive of broad phenotypic severity, we demonstrated that most vascular
      anomalies with overgrowth harbor postzygotic gain-of-function mutations in
      oncogenes. Furthermore, continued interrogation of oncogenes in benign
      developmental disorders could provide insight into fundamental mechanisms
      regulating cell growth.

PMID- 29174370
TI  - Decreased Skin Barrier Lipid Acylceramide and Differentiation-Dependent Gene
      Expression in Ichthyosis Gene Nipal4-Knockout Mice.
AB  - NIPAL4 is one of the causative genes for autosomal recessive congenital
      ichthyosis. However, the role of NIPAL4 in skin barrier formation and the
      molecular mechanism of ichthyosis pathology caused by NIPAL4 mutations, have not
      yet been determined. Here, we found that Nipal4-knockout (KO) mice exhibited
      neonatal lethality due to skin barrier defects. Histological analyses showed
      several morphological abnormalities in the Nipal4-KO epidermis, including
      impairment of lipid multilayer structure formation, hyperkeratosis, immature
      keratohyalin granules, and developed heterochromatin structures. The levels of
      the skin barrier lipid acylceramide were decreased in Nipal4-KO mice. Expression
      of genes involved in skin barrier formation normally increases during
      keratinocyte differentiation, in which chromatin remodeling is involved. However,
      the induction of Krt1, Lor, Flg, Elovl1, and Dgat2 was impaired in Nipal4-KO
      mice. NIPAL4 is a putative Mg2+ transporter, and Mg2+ concentration in
      differentiated keratinocytes of Nipal4-KO mice was indeed lower than that of wild
      type mice. Our results suggest that low Mg2+ concentration causes aberration in
      the proper chromatin remodeling process, which in turn leads to failure of
      differentiation-dependent gene induction in keratinocytes. Our findings provide
      insights into Mg2+-dependent regulation of gene expression and skin barrier
      formation during keratinocyte differentiation.

PMID- 29174371
TI  - Cooperativity of HOXA5 and STAT3 Is Critical for HDAC8 Inhibition-Mediated
      Transcriptional Activation of PD-L1 in Human Melanoma Cells.
AB  - Although the expression of programmed death-ligand 1 (PD-L1) is an important
      mechanism by which cancer cells evade the immune system, PD-L1 expression in
      cancer cells is commonly associated with patients' responses to treatment with
      anti-programmed death 1/PD-L1 antibodies. However, how PD-L1 expression is
      regulated in melanoma cells remains to be fully elucidated. Here we report that
      the class I histone deacetylase (HDAC) HDAC8 controls transcriptional activation
      of PD-L1 by a transcription complex consisting of transcription factors homeobox
      A5 and signal transducer and activator of transcription 3. Inhibition of HDAC8
      upregulated PD-L1 in melanoma cells. This was due to an increase in the activity
      of a fragment of the PD-L1 gene promoter that is enriched with binding sites for
      both homeobox A5 and signal transducer and activator of transcription 3. Indeed,
      knockdown of homeobox A5 or signal transducer and activator of transcription 3
      abolished upregulation of PD-L1 by HDAC8 inhibition. Moreover, homeobox A5 and
      signal transducer and activator of transcription 3 were physically associated and
      appeared interdependent in activating PD-L1 transcription. Functional studies
      showed that HDAC8-mediated regulation of PD-L1 expression participated in
      modulating anti-melanoma T-cell responses. Collectively, these results identify
      HDAC8 as an important epigenetic regulator of PD-L1 expression, with implications
      for better understanding of the interaction between melanoma cells and the immune
      system.

PMID- 29174372
TI  - Changing health care costs for NSCLC, what does it mean?

PMID- 29174373
TI  - Sara Lustigman: Developing a vaccine to accelerate onchocerciasis elimination.

PMID- 29174374
TI  - Tracheobronchial stenting for airway malacia.
AB  - Tracheobronchomalacia is a rare but clinically troublesome condition in
      paediatrics. The softening of the major airways - which can include some or all
      of the tracheobronchial tree can lead to symptoms ranging from the minor (harsh
      barking cough, recurrent chest infections) to severe respiratory difficulties
      including prolonged ventilator support and 'near death attacks'. The causes are
      broadly divided into intrinsic softening of the airway wall which is considered a
      primary defect (e.g. syndromes; post tracheo-oesophageal fistula repair; extreme
      prematurity) or secondary malacia due to external compression from vascular
      structures or cardiac components. These secondary changes can persist even when
      the external compression is relieved, for example, following the repair of a
      pulmonary artery sling or double aortic arch. For children with severe clinical
      symptoms attributed to malacia, consideration is given to possible surgical
      remedies such as an aortopexy for short limited areas of malacia, or long term
      positive pressure support with CPAP either by non invasive or tracheostomy
      interface. More recently the role of stenting in children is receiving attention,
      especially with the development of newer techniques such as bioabsorbable stents
      which buy time for a natural history of improvement in the malacia to occur. This
      paper reviews the stents available and discusses the pros and cons of stenting in
      paediatric airway malacia.

PMID- 29174375
TI  - Actinidia arguta extract attenuates inflammasome activation: Potential
      involvement in NLRP3 ubiquitination.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Actinidia arguta (A. arguta) has been widely used
      in Asian countries as a traditional medicinal herb to treat inflammation-related
      diseases, such as gastritis, bronchitis, and arthritis. AIM OF THE STUDY: The
      inhibitory effect of A. arguta leaves' extract (AA) on inflammasome activation
      was investigated to verify its traditional use in treating inflammation-related
      diseases. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) primed
      by lipopolysaccharide (LPS) were activated by selective inflammasome stimulators,
      and the effect of AA on inflammasome activation was investigated. A monosodium
      urate crystal (MSU)-induced peritonitis mouse model was used to study the in vivo
      efficacy of AA on inflammasome activation. RESULTS: In the in vitro study, AA
      regulated NLRP3 ubiquitination and apoptosis-associated speck-like protein
      containing a CARD (ASC) oligomerization, leading to the inhibition of NLRP3
      inflammasome-mediated interleukin (IL)-1beta secretion. The inhibitory effect of
      AA on inflammasome activation in vitro was further confirmed in vivo using an MSU
      induced peritonitis mouse model. CONCLUSION: AA provided scientific evidence,
      substantiating the traditional claims for its use in the treatment of
      inflammation and inflammation-mediated metabolic disorders, including gout.

PMID- 29174376
TI  - Evidence of reduced bladder capacity during nighttime in children with
      monosymptomatic nocturnal enuresis.
AB  - INTRODUCTION: Bladder capacity in children with nocturnal enuresis is assessed by
      maximal voided volumes (MVV) obtained through daytime frequency volume (FV)
      charts. Although a degree of association has been demonstrated, daytime MVV does
      not consistently correspond with the nocturnal bladder capacity (NBC) in
      monosymptomatic nocturnal enuresis (MNE). It was hypothesized that isolated
      reduced NBC is a common phenomenon in children with nocturnal enuresis, despite
      normal daytime bladder function. OBJECTIVE: The aim of this study was to evaluate
      NBC in children with MNE and normal daytime voided volumes. Specifically, it
      aimed to determine the prevalence and degree of reduced NBC when using nocturnal
      urine production (NUP) during wet nights as a surrogate estimate of NBC.
      Furthermore, it aimed to investigate the relationship between NBC and
      desmopressin response. MATERIALS AND METHODS: Data from 103 children aged 5-15
      years consecutively treated for MNE in a tertiary referral centre and with normal
      MVV on daytime FV charts were collected for this cohort study. Home recordings
      were completed for 2 weeks at baseline and during desmopressin dose titration.
      Estimated nocturnal bladder capacity (eNBC) was assessed separately each night as
      the total NUP causing a wet night. If NUP during a wet night was less than MVV,
      it was considered to be reduced eNBC during that particular night. RESULTS:
      Surprisingly, 82% (n = 84) of the children with MNE and normal daytime MVV
      experienced at least one wet night, with NUP below the daytime MVV indicative of
      a reduced eNBC. For 84 patients, mean percentage of wet nights with reduced eNBC
      (NUP below MVV) was 49% (SD +/- 31). A total of 11% of children with frequently
      reduced eNBC (>40% of wet nights with reduced eNBC) responded to desmopressin
      (Summary Fig.). Of the children with frequently reduced NBC, 91% experienced wet
      nights, with NUP <65% of expected bladder capacity (EBC). CONCLUSIONS: A
      significant proportion of children with MNE and normal MVV during the daytime
      frequently experienced wet nights, with a NUP well below their MVV and even <65%
      of EBC. This indicated that bladder reservoir dysfunction during sleep is
      relatively common in MNE. This abnormality was not reflected on daytime
      recordings, and thus nighttime data with NUP must be collected. This phenomenon
      may explain treatment failure to desmopressin, despite adequate antidiuretic
      response.

PMID- 29174377
TI  - Testosterone prior to hypospadias repair: Postoperative complication rates and
      long-term cosmetic results, penile length and body height.
AB  - INTRODUCTION: The use of hormonal therapy was first described in 1971 before
      hypospadias surgery, and it has been debated ever since. The long-term outcomes
      after puberty of patients treated with pre-operative testosterone in childhood
      are lacking. OBJECTIVES: Possible long-term effects of testosterone are often
      asked about in daily practice. The current study investigated the long-term
      outcomes regarding height, penile length and penile cosmesis in adult men after
      hypospadias surgery in childhood with and without pre-operative testosterone.
      METHODS: Adult men (n = 121) who underwent primary hypospadias repair in
      childhood were included. Pre-operative penile appearance, judged by a paediatric
      urologist, determined the use of pre-operative testosterone. Data on hypospadias
      characteristics, healing complications, surgical repair, and testosterone use
      were collected retrospectively. At adult age, stretched penile length and body
      height were measured, and penile cosmesis was evaluated using the Pediatric
      Penile Perception Score (PPPS). RESULTS: Postoperative complication rates in
      patients (n = 121) with and without testosterone were similar (50% vs. 43%; P =
      0.54). Sixty adult patients (50%) with a median age of 19.8 years and follow-up
      time of 18.3 years were examined at the outpatient clinic at adult age. Of this
      group, testosterone was applied in 12/43 patients with distal, 3/6 patients with
      midshaft, and 9/11 patients with proximal hypospadias. Adult stretched penile
      length (12.0 cm vs. 12.4 cm; P = 0.47) and adult height (180.1 cm vs. 179.0 cm P
      = 0.65) showed no difference between patients with and without testosterone
      treatment. Penile cosmesis was (very) satisfactory in all PPPS domains, and
      showed no difference between the testosterone group and the non-testosterone
      group. Univariate and multivariate analysis was conducted to determine if the
      hypospadias type or pre-operative testosterone therapy had more influence on the
      long-term outcomes. None of the long-term outcomes were significantly associated
      with pre-operative testosterone therapy on multivariate analysis. DISCUSSION:
      This was the first study reporting long-term outcomes of hypospadias patients
      after puberty who received pre-operative hormonal therapy. Validated instruments
      were used as much as possible. Shortcomings of this study were the 50% response
      rate, the retrospective design, and the lack of objective inclusion criteria
      reported to indicate pre-operative testosterone therapy. CONCLUSION: This study
      suggested that the long-term results of patients receiving pre-operative
      testosterone treatment, who often had more challenging hypospadias, were similar
      to those who did not. However, a randomised controlled study is needed to confirm
      these results.

PMID- 29174379
TI  - A new pathway to eSCAPe lipotoxicity.
AB  - The molecular mechanisms underlying fatty liver progression towards more severe
      syndromes are complex and only partially understood. Studies have recently
      reported that lipotoxic fatty acid metabolites are instrumental in the
      development of hepatocyte injury in the context of fatty liver disease. The
      recent study by Papazyan et al. published in Cell Metabolism (2016;24(6):863-874)
      addresses this issue and reveals that rescuing de novo fatty acid synthesis
      (lipogenesis) through the activation of the transcription factor SREBP-1c can
      prevent lethality as well as severe lipotoxicity caused by a combined deficiency
      in lipogenesis and beta-oxidation. Altogether, this study reveals that optimizing
      lipid signals generated by lipogenesis through SREBP-1c can help redirect fatty
      acids toward beneficial actions, by buffering lipotoxic lipid intermediates even
      in the setting of lipid overload.

PMID- 29174378
TI  - Standardization of pediatric uroradiological terms: A multidisciplinary European
      glossary.
AB  - To promote the standardization of nephro-uroradiological terms used in children,
      the European Society of Pediatric Radiology uroradiology taskforce wrote a
      detailed glossary. This work has been subsequently submitted to European experts
      in pediatric urology and nephrology for discussion and acceptance to improve the
      quality of radiological reports and communication among different clinicians
      involved in pediatric urology and nephrology.

PMID- 29174380
TI  - Effect of heme oxygenase-1 on the protection of ischemia reperfusion injury of
      bile duct in rats after liver transplantation.
AB  - OBJECTIVE: To investigate the effect of heme oxygenase-1 (HO-1) on the ischemic
      reperfusion injury (IRI) of bile duct in rat models after liver transplantation.
      METHODS: 320 SD rats were equally and randomly divided into 5 groups, which were
      group A receiving injection of 3*108/pfu/ml adenovirus (adv), group B with donor
      receiving Adv-HO-1 and recipient receiving Adv-HO-1-siRNA, group C with donor and
      recipient both receiving Adv-HO-1, group D with donor receiving Adv-HO-1-siRNA
      and recipient receiving Adv-HO-1, and group E with donor and recipient both
      receiving Adv-HO-1-siRNA at 24h before liver transplantation. Donor liver was
      stored in UW liquid at 4 degrees C followed by measuring HO-1 level by western
      blot before transplantation. On d1, d3, d7 and d14, serum and liver was isolated
      for analysis of liver function, inflammatory cell infiltration by H&E staining,
      ultrastructure of liver by transmission electron microscopy as well as the
      expression of HO-1, Bsep, Mrp2 and Ntcp by western blot. RESULTS: Compared with
      group D and E, group B and C displayed improved liver function as demonstrated by
      lower level of ALT, AST, LDH, TBIL, ALP and GGT, increased secretion of TBA and
      PL as well as expression of transporter proteins (Bsep, Mrp2 and Ntcp), reduced
      inflammatory cells infiltration and liver injury. CONCLUSION: Our study
      demonstrated that overexpression of HO-1 in donor liver can ameliorate the damage
      to bile duct and liver, and improved liver function, suggesting HO-1 might be a
      new therapeutic target in the treatment of IRI after liver transplantation.

PMID- 29174381
TI  - Anti-neuroinflammatory effect of 6,8,1'-tri-O-methylaverantin, a metabolite from
      a marine-derived fungal strain Aspergillus sp., via upregulation of heme
      oxygenase-1 in lipopolysaccharide-activated microglia.
AB  - In the course of searching for anti-neuroinflammatory metabolites from marine
      derived fungi, three fungal metabolites, 6,8,1'-tri-O-methylaverantin, 6,8-di-O
      methylaverufin, and 5-methoxysterigmatocystin were isolated from a marine-derived
      fungal strain Aspergillus sp. SF-6796. Among these, 6,8,1'-tri-O-methylaverantin
      induced the expression of heme oxygenase (HO)-1 protein in BV2 microglial cells.
      The induction of HO-1 protein was mediated by the activation of nuclear
      transcription factor erythroid-2 related factor 2 (Nrf2), and was regulated by
      the p38 mitogen-activated protein kinase and phosphatidylinositol 3
      kinase/protein kinase B signaling pathways. Furthermore, 6,8,1'-tri-O
      methylaverantin suppressed the overproduction of pro-inflammatory mediators, such
      as nitric oxide, prostaglandin E2, inducible nitric oxide synthase, and
      cyclooxygenase-2 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells.
      These anti-neuroinflammatory effects were mediated through the negative
      regulation of the nuclear factor kappa B pathway, repressing the phosphorylation
      and degradation of inhibitor kappa B-alpha, translocation into the nucleus of
      p65/p50 heterodimer, and DNA-binding activity of p65 subunit. The anti
      neuroinflammatory effect of 6,8,1'-tri-O-methylaverantin was partially blocked by
      a selective HO-1 inhibitor, suggesting that its anti-neuroinflammatory effect is
      at least partly mediated by HO-1 induction. In this study, 6,8,1'-tri-O
      methylaverantin also induced HO-1 protein expression in primary microglial cells,
      and this correlated with anti-neuroinflammatory effects observed in LPS
      stimulated primary microglial cells. In conclusion, 6,8,1'-tri-O-methylaverantin
      represents a potential candidate for use in the development of therapeutic agents
      for the regulation of neuroinflammation in neurodegenerative diseases.

PMID- 29174382
TI  - Methylated flavonoids as anti-seizure agents: Naringenin 4',7-dimethyl ether
      attenuates epileptic seizures in zebrafish and mouse models.
AB  - Epilepsy is a neurological disease that affects more than 70 million people
      worldwide and is characterized by the presence of spontaneous unprovoked
      recurrent seizures. Existing anti-seizure drugs (ASDs) have side effects and fail
      to control seizures in 30% of patients due to drug resistance. Hence, safer and
      more efficacious drugs are sorely needed. Flavonoids are polyphenolic structures
      naturally present in most plants and consumed daily with no adverse effects
      reported. These structures have shown activity in several seizure and epilepsy
      animal models through allosteric modulation of GABAA receptors, but also via
      potent anti-inflammatory action in the brain. As such, dietary flavonoids offer
      an interesting source for ASD and anti-epileptogenic drug (AED) discovery, but
      their pharmaceutical potential is often hampered by metabolic instability and low
      oral bioavailability. It has been argued that their drug-likeness can be improved
      via methylation of the free hydroxyl groups, thereby dramatically enhancing
      metabolic stability and membrane transport, facilitating absorption and highly
      increasing bioavailability. Since no scientific data is available regarding the
      use of methylated flavonoids in the fight against epilepsy, we studied naringenin
      (NRG), kaempferol (KFL), and three methylated derivatives, i.e., naringenin 7-O
      methyl ether (NRG-M), naringenin 4',7-dimethyl ether (NRG-DM), and kaempferide
      (4'-O-methyl kaempferol) (KFD) in the zebrafish pentylenetetrazole (PTZ) seizure
      model. We demonstrate that the methylated flavanones NRG-DM and NRG-M are highly
      effective against PTZ-induced seizures in larval zebrafish, whereas NRG and the
      flavonols KFL and KFD possess only a limited activity. Moreover, we show that NRG
      DM is active in two standard acute mouse seizure models, i.e., the timed i.v. PTZ
      seizure model and the 6-Hz psychomotor seizure model. Based on these results, NRG
      DM is proposed as a lead compound that is worth further investigation for the
      treatment of generalized seizures and drug-resistant focal seizures. Our data
      therefore highlights the potential of methylated flavonoids in the search for new
      and improved ASDs.

PMID- 29174383
TI  - Intracerebroventricular streptozotocin impairs adult neurogenesis and cognitive
      functions via regulating neuroinflammation and insulin signaling in adult rats.
AB  - Neurogenesis is a complex process involved in memory formation and is known to be
      altered in Alzheimer's disease (AD). Neuroinflammation and insulin signaling
      dysfunction, key players during intracerebroventricular Streptozotocin (ICV-STZ)
      induced dementia variedly affects neurogenesis. The aim of this work was to study
      the variation in neurogenic process associated with AD in ICV STZ induced
      dementia. Adult male Sprague Dawley rats weighing 180-200 g were given two
      different doses of ICV STZ (3 mg/kg on Day 1 and 3, & 1 mg/kg on Day 1) in two
      different experimental setup. Memory functions were assessed by Morris Water
      Maze. Immunofluorescence and western blotting was done to study the variation in
      neurogenesis, amyloid and tau pathology, neuroinflammation and insulin signaling.
      ICV STZ 6 mg/kg (3 mg/kg twice on Day 1 and 3 of 21 days study) caused impairment
      in learning and memory and severe atrophy of the neurogenic areas. Modified dose
      of ICV STZ (1 mg/kg once on Day 1) caused a significant decline in neurogenesis
      in subventricular zone (SVZ) and dentate gyrus (DG) as indicated by decrease in
      the number of (5-Bromo-2'-deoxyuridine) BrdU+ Nestin+ cells, Doublecortin (DCX+)
      cells and BrdU+ NeuN+ cells after day 11 and 18 of ICV STZ injection. However,
      impairment in learning and memory was observed only during 18 days study post ICV
      STZ injection (1 mg/kg on Day 1). Up regulation of proteins of amyloid and tau
      pathology (Amyloid precursor protein (APP), beta site amyloid precursor protein
      cleaving enzyme 1 (BACE1) & p-Tau Ser 396) was observed at this time point with
      no significant change in amyloid beta42 (Abeta42) expression. Enhanced
      neuroinflammation (increased Glial fibrillary acidic protein (GFAP) & nuclear
      factor kappa-light-chain-enhancer of activated B cells (NFkappaB)) and diminished
      insulin signaling was also observed in our study in both neurogenic areas,
      however the extent to which they may have negative impact on neurogenes is yet to
      be explored.

PMID- 29174384
TI  - Reduction of MRI signal distortion from titanium intracavitary brachytherapy
      applicator by optimizing pulse sequence parameters.
AB  - PURPOSE: To demonstrate that optimized pulse sequence parameters for a T2
      weighted (T2w) fast spin echo acquisition reduced artifacts from a titanium
      brachytherapy applicator compared to conventional sequence parameters. METHODS
      AND MATERIALS: Following Institutional Review Board approval and informed
      consent, seven patients were successfully imaged with both standard sagittal T2w
      fast spin echo parameters (voxel size of 0.98 * 0.78 * 4.0 mm3; readout bandwidth
      of 200 Hz/px; repetition time of 2800 ms; echo time of 91 ms; echo train length
      of 15; 36 slices; and imaging time of 3:16 min) and an additional optimized T2w
      sequence (voxel size of 0.98 * 0.98 * 4.0 mm3; readout bandwidth of 500 Hz/px;
      repetition time of 3610 ms; echo time of 91 ms; echo train length of 25; 18-36
      slices; and imaging time of 1:15-2:30 min), which had demonstrated artifact
      reduction in prior phantom work. Visualized intracavitary tandem was hand
      segmented by two of the authors. Three body imaging radiologists assessed image
      quality and intraobserver agreement scores were analyzed. RESULTS: The average
      segmented volume of the intracavitary applicator significantly (p < 0.05)
      decreased with the experimental pulse sequence parameters as compared to the
      standard pulse sequence. Comparison of experimental and standard T2w sequence
      qualitative scores for each reviewer showed no significant differences between
      the two techniques. CONCLUSIONS: This study demonstrated that pulse sequence
      parameter optimization can significantly reduce distortion artifact from titanium
      applicators while maintaining image quality and reasonable imaging times.

PMID- 29174385
TI  - Dose warping uncertainties for the accumulated rectal wall dose in cervical
      cancer brachytherapy.
AB  - PURPOSE: Structure-based deformable image registration (DIR) can be used to
      calculate accumulated dose volume histogram parameters for cervical cancer
      brachytherapy (BT). The purpose of this study is to investigate dose warping
      uncertainties for the accumulated dose to the 2 cm3 receiving the highest dose
      [Formula: see text] in the rectal wall, using a physically realistic model (PRM)
      describing rectal wall deformation. METHODS AND MATERIALS: For 10 patients,
      treated with MRI-guided pulsed dose rate BT (two times 24 * 0.75 Gy, given in two
      applications BT1 and BT2), the planning images were registered with structure
      based DIR. The resulting transformation vectors were used to accumulate the total
      rectum dose from BT. To investigate the dose warping uncertainty, a PRM
      describing rectal deformation was used. For point pairs on rectumBT1 and
      rectumBT2 that were at the same location according to the PRM, the dose for BT1
      and BT2 was added (DPRM) and compared to the DIR-accumulated dose (DDIR) in the
      BT2 point. The remaining distance after DIR between corresponding point pairs,
      defined as the residual distance, was calculated. RESULTS: For points within the
      [Formula: see text] volume, more than 75% was part of the [Formula: see text]
      volume according to both PRM and DIR. The absolute dose difference was <7.3
      GyEQD2, and the median (95th percentile) of the residual distance was 8.7 (22)
      mm. CONCLUSIONS: DIR corresponded with the PRM for on average 75% of the
      [Formula: see text] volume. Local absolute dose differences and residual
      distances were large. Care should therefore be taken with DIR for dose-warping
      purposes in BT.

PMID- 29174386
TI  - Expression and cellular localization of double sex and mab-3 related
      transcription factor 1 in testes of postnatal Small-Tail Han sheep at different
      developmental stages.
AB  - : Double sex and mab-3 related transcription factor 1 (Dmrt1), an evolutionarily
      conserved gene, is a sex-related gene expressed in male gonads, that is involved
      in the regulation of sex differentiation, testicular development and reproductive
      function maintenance. Until now, functional studies on the Dmrt1 gene in sheep
      (Ovis aries) have been lacking. In this study, testis, heart, liver, spleen,
      lung, kidney and longissimus dorsi muscle tissues were collected from Small-Tail
      Han sheep at 0, 2, 5, 12 and 24months after birth (mab). Dmrt1 expression and
      cellular localization were detected in various testicular tissues by quantitative
      real time PCR (qRT-PCR), western blot and immunohistochemistry methods. The
      morphological structures of testicular tissues at different developmental stages
      were observed by hematoxylin & eosin (HE) staining. The Dmrt1 mRNA expression
      levels in 12 and 24 mab sheep were significantly higher than those in 0 and 2 mab
      sheep (P<0.05), and Dmrt1 protein expression showed a similar trend. The qRT-PCR
      results in various tissues at 12 mab showed that Dmrt1 mRNA was predominantly
      expressed in testes. Immunohistochemical staining in testes at different
      developmental stages showed that Dmrt1 protein immunoreactive responses were
      mainly localized in Sertoli cells and gonocytes at 0, 2 and 5 mab, while they
      were localized in spermatocytes, sperm cells and some spermatogonia and Sertoli
      cells at 12 and 24 mab. We speculate that the Dmrt1 gene plays a vital role in
      postnatal sheep spermatogenesis, perhaps by regulating the maturation and
      functional maintenance of Sertoli cells, the proliferation and differentiation of
      gonocytes in prepubertal sheep testes, and the mitosis and meiosis of germ cells
      in adult sheep, but the specific mechanisms underlying these phenomena must be
      further studied and verified. ABBREVIATIONS: 

PMID- 29174387
TI  - Role of tumor necrosis factor-alpha in epithelial-to-mesenchymal transition in
      transplanted kidney cells in recipients with chronic allograft dysfunction.
AB  - BACKGROUND: Chronic allograft dysfunction (CAD) is characterized by allograft
      kidney interstitial fibrosis, the underlying mechanism of which is unclear. Our
      aim was to elucidate the role and mechanism of TNF-alpha-induced epithelial-to
      mesenchymal transition (EMT) in transplant kidney tubular interstitial fibrosis.
      METHODS: Human kidney tissues from normal volunteers and CAD patients were
      assessed using periodic acid-Schiff, Masson trichrome and immunohistochemical
      staining. mRNA and protein expression of E-cadherin, alpha-smooth muscle actin
      (SMA) and fibronectin(FN) in renal proximal tubule epithelial (HK-2) cells after
      treatment with TNF-alpha under different conditions were assessed using western
      blot and qRT-PCR analysis. Cell motility and migration were assessed using wound
      healing and transwell assays. Expression of Smurf2 and TNF-alpha-signaling
      pathway-related proteins in HK-2 cells treated with TNF-alpha was detected by
      western blotting. E-cadherin and alpha-SMA expression was also assessed in Smurf2
      plasmid-transfected or Smurf2 siRNA-treated HK-2 cells. RESULTS: The expression
      of TNF-alpha, Smurf2, alpha-SMA, and fibronectin was significantly upregulated,
      while the expression of E-cad was downregulated in the CAD group compared with
      the normal group. The in vitro results showed that TNF-alpha remarkably
      upregulated the expression of Smurf2, alpha-SMA and fibronectin and downregulated
      the expression of E-cadherin in HK-2 cells and enhanced motility and migration in
      HK-2 cells. Overexpression of Smurf2 could promote the expression of alpha-SMA
      and inhibit the expression of E-cad, whereas knockdown of Smurf2 expression
      reversed TNF-alpha-induced upregulation of alpha-SMA and prohibited the reduction
      of E-cad expression. Furthermore, TNF-alpha-induced Smurf2 expression promoted
      EMT through the Akt signaling pathway. CONCLUSIONS: TNF-alpha induced EMT via the
      TNF-alpha/Akt/Smurf2 signaling pathways, and it may play a role in aggravating
      allograft kidney interstitial fibrosis in CAD patients.

PMID- 29174388
TI  - Smokers' identity and quit advice in general practice: General practitioners need
      to focus more on female smokers.
AB  - OBJECTIVE: We examined smoker and non-smoker self-identities among smokers
      visiting their general practitioner (GP) for other reasons than smoking cessation
      counselling. We determined whether identity impacted on patients' appreciation of
      GP-initiated conversations about smoking and quit advice, and subsequent quit
      attempts, and examined the role of gender. METHODS: Secondary analyses of a
      cluster-randomised controlled trial in which baseline and 12-month follow-up data
      were collected among 527 daily (n=450) and non-daily smokers (n=77). RESULTS:
      Participants identified more with smoking than non-smoking. Participants with
      stronger non-smoker self-identities were more often female, appreciated the
      conversation about smoking more, were more likely to receive quit-advice and to
      have attempted to quit at 12-month follow-up. Participants with stronger smoker
      self-identities were also more often female, and appreciated the conversation
      more. Men with stronger non-smoker self-identities were more often asked about
      smoking and advised to quit, and appreciated the conversation more than women.
      CONCLUSION: Non-smoker identity was more important for receiving quit-advice,
      appreciation, and quit attempts than smoker identity. Future research needs to
      unravel why female smokers appreciated the conversation less than male smokers.
      PRACTICE IMPLICATIONS: We suggest to incorporate an identity-component in smoking
      cessation interventions. GPs should increase their focus on female patients who
      smoke.

PMID- 29174389
TI  - Temporal variability in lipoprotein(a) levels in patients enrolled in the placebo
      arms of IONIS-APO(a)Rx and IONIS-APO(a)-LRx antisense oligonucleotide clinical
      trials.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] levels are primarily genetically determined,
      but their natural variability is not well known. OBJECTIVE: The aim of the study
      was to evaluate the short-term temporal variability in Lp(a) in 3 placebo groups
      from the IONIS-APO(a)Rx and IONIS-APO(a)-LRx trials. METHODS: The placebo groups
      comprised 3 studies: Study 1 with 10 subjects with any Lp(a) concentration; Study
      2 with 13 subjects with Lp(a) >=75 nmol/L (~30 mg/dL); and Study 3 with 29
      patients with Lp(a) >=125 nmol/L (>=~50 mg/dL). Lp(a) was measured in serial
      blood samples (range 7-12 samples up to 190 days of follow-up) and analyzed as
      absolute change and mean percent change from baseline. Outliers were defined as
      having a > +/-25% difference in Lp(a) from baseline at any future time point.
      RESULTS: No significant temporal differences in mean absolute Lp(a) levels were
      present in any group. However, among individuals, the mean change in absolute
      Lp(a) levels at any time point ranged from -16.2 to +7.0 nmol/L in Study 1, -15.8
      to +9.8 nmol/L in Study 2, and -60.2 to +16.6 nmol/L in Study 3. The mean percent
      change from baseline ranged from -9.4% to +21.6% for Study 1, -13.1% to 2.8% for
      Study 2, and -12.1% to +4.9% in Study 3. A total of 21 of 52 subjects (40.4%)
      were outliers, with 13 (62%) >25% up and 8 (38%) >25% down. Significant
      variability was also noted in other lipid parameters, but no outliers were noted
      with serum albumin. CONCLUSION: In subjects randomized to placebo in Lp(a)
      lowering trials, modest intra-individual temporal variability of mean Lp(a)
      levels was present. Significant number of subjects had > +/-25% variation in
      Lp(a) in at least 1 time point. Although Lp(a) levels are primarily genetically
      determined, further study is required to define additional factors mediating
      short-term variability.

PMID- 29174390
TI  - Direct Aortic Access for Transcatheter Aortic Valve Replacement Using a Self
      Expanding Device.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) using a self-expanding
      valve has been shown to be superior to an open operation in high-risk patients.
      Extensive iliofemoral peripheral vascular disease can prohibit femoral access. In
      these cases, direct aortic (DA) implantation may be a suitable option. METHODS:
      The current analysis compared outcomes in patients undergoing TAVR with the self
      expanding CoreValve prosthesis (Medtronic, Minneapolis, MN) by direct aortic (DA)
      access vs iliofemoral (IF) access. Patients treated in the CoreValve US High Risk
      and Extreme Risk Pivotal Trials and Continued Access Study were included.
      Propensity score matching was used to account for differences in baseline
      characteristics between groups. Clinical outcomes were compared at 30 days and 1
      year. RESULTS: We identified 394 matched pairs of IF and DA patients. The all
      cause mortality rate was significantly higher in the DA group than in the IF
      group at 30 days (10.9% vs 4.1%, p < 0.001), but this difference was reduced at 1
      year (28.1% vs 23.2%, p = 0.063). All-cause mortality or major stroke was
      significantly higher for DA vs IF access at 30 days (13.5% vs 5.3%, p < 0.001)
      and at 1 year (30.4% vs 24.2%, p = 0.025). Major/life-threatening bleeding and
      acute kidney injury were significantly greater in the DA group at 30 days (66.7%
      vs 35.4% and 19.7% vs 10.0%, respectively, both p < 0.001). CONCLUSIONS: When
      femoral access is not feasible, DA access allows effective delivery of the valve
      but incurs an increased risk of death and adverse events, potentially the result
      of procedural differences.

PMID- 29174391
TI  - Prediction of Long-Term Survival After Lung Cancer Surgery for Elderly Patients
      in The Society of Thoracic Surgeons General Thoracic Surgery Database.
AB  - BACKGROUND: Prior risk models using the STS General Thoracic Surgery database
      (STS-GTSD) have been limited to 30-day outcomes. We have now linked STS data to
      Medicare data and sought to create a risk prediction model for long-term
      mortality after lung cancer resection in patients older than 65 years. METHODS:
      The STS-GTSD was linked to Medicare data for lung cancer resections from 2002 to
      2013 as previously reported. Successful linkage was performed in 29,899 lung
      cancer resection patients. Cox proportional hazards modeling was used to create a
      long-term survival model. Variable selection was performed using statistically
      significant univariate factors and known clinical predictors of outcome.
      Calibration was assessed by dividing the cohort into deciles of predicted
      survival and discrimination assessed with a C-statistic corrected for optimism
      via 1,000 bootstrap replications. RESULTS: Median age was 73 years (interquartile
      range, 68 to 78 years), and 48% of the patients were male. Of the 29,094 patients
      with nonmissing pathologic stage, 69% were stage I, 18% stage II, 11% stage III,
      and 2% stage IV. Procedure performed was lobectomy in 69%, bilobectomy in 3%,
      pneumonectomy in 3%, segmentectomy in 7%, sleeve lobectomy in 1%, and wedge
      resection in 17%. Thoracoscopic approach was performed in 47% of resections. The
      final Cox model reveals that stage and age are the strongest predictors of long
      term survival. Even after controlling for stage, wedge resection, segmentectomy,
      bilobectomy, and pneumonectomy are all associated with increased hazard of death
      in comparison with lobectomy. Thoracoscopic approach is associated with improved
      long-term survival in comparison with thoracotomy. Other modifiable predictive
      factors include smoking and low body mass index. Calibration of the model
      demonstrates excellent performance across all survival deciles and a C-statistic
      of 0.694. CONCLUSIONS: The STS-GTSD-Medicare long-term risk model includes
      several novel factors associated with mortality. Although medical factors predict
      long-term survival, age and stage are the strong predictors. Despite this,
      procedure choice and thoracoscopic/open approach are potentially modifiable
      predictors of long-term survival after lung cancer resection.

PMID- 29174392
TI  - Reply to: "Prognostic value of lipoprotein-associated phospholipase A2 mass for
      all-cause mortality and vascular events within one year after acute ischemic
      stroke: Methodological issues".

PMID- 29174393
TI  - Reply to: "PCSK9 antagonists and inflammation".

PMID- 29174394
TI  - Visual and binocular status in elementary school children with a reading problem.
AB  - PURPOSE: This descriptive study provides a summary of the binocular anomalies
      seen in elementary school children identified with reading problems. METHODS: A
      retrospective chart review of all children identified with reading problems and
      seen by the University of Waterloo, Optometry Clinic, from September 2012 to June
      2013. RESULTS: Files of 121 children (mean age 8.6 years, range 6-14 years) were
      reviewed. No significant refractive error was found in 81% of children. Five and
      8 children were identified as strabismic at distance and near respectively.
      Phoria test revealed 90% and 65% of patients had normal distance and near phoria.
      Near point of convergencia (NPC) was <5cm in 68% of children, and 77% had
      stereoacuity of <=40seconds of arc. More than 50% of the children had normal
      fusional vergence ranges except for near positive fusional vergencce (base out)
      break (46%). Tests for accommodation showed 91% of children were normal for
      binocular facility, and approximately 70% of children had an expected accuracy of
      accommodation. CONCLUSION: Findings indicate that some children with an
      identified reading problem also present with abnormal binocular test results
      compared to published normal values. Further investigation should be performed to
      investigate the relationship between binocular vision function and reading
      performance.

PMID- 29174395
TI  - Normalization of mass spectrometry data (NOMAD).
AB  - iTRAQ and TMT reagent-based mass spectrometry (MS) are commonly used technologies
      for quantitative proteomics in biological samples. Such studies are often
      performed over multiple MS runs, potentially resulting in introduction of MS run
      bias that could affect downstream analysis. Such MS data have therefore commonly
      been normalized using a reference sample which is included in each MS run. We
      show, however, that reference normalization does not effectively remove
      systematic MS run bias. A linear model approach was previously proposed to
      improve on the reference normalization approach but does not computationally
      scale to larger data sets. Here we describe the NOMAD (normalization of mass
      spectrometry data) R package which implements a computationally efficient ANOVA
      normalization approach with protein assembly functionality. NOMAD provides the
      same advantages as the linear regression solution but is more computationally
      efficient which allows superior scaling to larger sample sizes. Moreover, NOMAD
      effectively removes bias which improves valid across MS run comparisons.

PMID- 29174396
TI  - PLCgamma1: Potential arbitrator of cancer progression.
AB  - Phospholipase C (PLC) is an essential mediator of cellular signaling. PLC
      regulates multiple cellular processes by generating bioactive molecules such as
      inositol-1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These products
      propagate and regulate cellular signaling via calcium (Ca2+) mobilization and
      activation of protein kinase C (PKC), other kinases, and ion channels. PLCgamma1,
      one of the primary subtypes of PLC, is directly activated by membrane receptors,
      including receptor tyrosine kinases (RTKs), and adhesion receptors such as
      integrin. PLCgamma1 mediates signaling through direct interactions with other
      signaling molecules via SH domains, as well as its lipase activity. PLCgamma1 is
      frequently enriched and mutated in various cancers, and is involved in the
      processes of tumorigenesis, including proliferation, migration, and invasion.
      Although many studies have suggested that PLCgamma functions in cell mobility
      rather than proliferation in cancer, questions remain as to whether PLCgamma
      regulates mitogenesis and whether PLCgamma promotes or inhibits proliferation.
      Moreover, how PLCgamma regulates cancer-associated cellular processes and the
      interplay among other proteins involved in cancer progression have yet to be
      fully elucidated. In this review, we discuss the current understanding of the
      role of PLCgamma1 in cancer mobility and proliferation.

PMID- 29174397
TI  - [Case-non case studies: Principles, methods, bias and interpretation].
AB  - Case-non case studies belongs to the methods assessing drug safety by analyzing
      the disproportionality of notifications of adverse drug reactions in
      pharmacovigilance databases. Used for the first time in the 1980s, the last few
      decades have seen a significant increase in the use of this design. The principle
      of the case-non case study is to compare drug exposure in cases of a studied
      adverse reaction with that of cases of other reported adverse reactions and
      called "non cases". Results are presented in the form of a reporting odds ratio
      (ROR), the interpretation of which makes it possible to identify drug safety
      signals. This article describes the principle of the case-non case study, the
      method of calculating the ROR and its confidence interval, the different
      modalities of analysis and how to interpret its results with regard to the
      advantages and limitations of this design.

PMID- 29174398
TI  - Assessment of the transmembrane domain structures in GPCR Dock 2013 models.
AB  - The community-wide blind prediction of G-protein coupled receptor (GPCR)
      structures and ligand docking has been conducted three times and the quality of
      the models was primarily assessed by the accuracy of ligand binding modes. The
      seven transmembrane (TM) helices of the receptors were taken as a whole; thus the
      model quality within the 7TM domains has not been evaluated. Here we evaluate the
      7TM domain structures in the models submitted for the last round of prediction -
      GPCR Dock 2013. Applying the 7 * 7 RMSD matrix analysis described in our prior
      work, we show that the models vary widely in prediction accuracy of the 7TM
      structures, exhibiting diverse structural differences from the targets. For the
      prediction of the 5-hydroxytryptamine receptors, the top 7TM models are rather
      close to the targets, which however are not ranked top by ligand-docking. On the
      other hand, notable deviations of the TMs are found in in the previously
      identified top docking models that closely resemble other receptors. We further
      reveal reasons of success and failure in ligand docking for the models. This
      current assessment not only complements the previous assessment, but also
      provides important insights into the current status of GPCR modeling and ligand
      docking.

PMID- 29174399
TI  - Better together: Contrasting the hypotheses explaining the one-target advantage.
AB  - Movement times are significantly shorter when moving from a start position to a
      single target, compared to when one has to continue onto a second target (i.e.,
      the one-target advantage [OTA]). To explain this movement time difference, both
      the movement integration and the movement constraint hypotheses have been
      proposed. Although both hypotheses have been found to have explanatory power as
      to why the OTA exists, the support for each has been somewhat equivocal. The
      current review evaluated the relative support in the literature for these two
      hypotheses. Ultimately, preferential support for each theoretical explanation was
      found to be related to the higher indices of difficulty (IDs: Fitts, 1954)
      employed. That is, studies that included higher IDs (i.e., 6-8 bits) were more
      likely to provide more support for the movement constraint hypothesis, whereas
      studies employing lower IDs (i.e., 1-4 bits) were more likely to provide more
      support for the movement integration hypothesis. When the IDs employed were
      relatively intermediate (i.e., 5 bits), both hypotheses were mostly supported.
      Thus, task difficulty is crucial when determining which hypothesis better
      explains the planning and control of sequential goal-directed movements.
      Critically, the OTA most likely always involves integration but may also involve
      constraining if the accuracy demands are sufficiently high.

PMID- 29174400
TI  - Self-assembled monolayer-based immunoassays for okadaic acid detection in
      seawater as monitoring tools.
AB  - Rapid and cost-effective methods to monitor the presence of diarrhetic shellfish
      poisoning (DSP) toxins in seawater samples in an easy and reliable manner are
      required to protect human health and avoid economic losses to shellfish industry.
      Immunoassays for the detection of okadaic acid (OA) and dinophysistoxin-1 and
      dinophysistoxin-2 are developed by immobilising OA on self-assembled monothiols
      or dithiols in an ordered and oriented way, providing an effective limit of
      detection of ~1 ng OA equiv./mL seawater. The immunoassays are applied to the
      analysis of the particulate fraction of seawater samples from two Catalan
      harbours (NW Mediterranean) and samples collected periodically from the Galician
      Rias (E Atlantic), as well as a reference mussel sample. Results are in agreement
      with LC-MS/MS and the certified values. OA concentration in seawater correlates
      with Dinophysis cell abundance, with a 1-2 weeks lag. The immunoassays provide
      powerful high-throughput analytical methods potentially applicable as alternative
      monitoring tools.

PMID- 29174401
TI  - The Gut Microbiota Facilitates Drifts in the Genetic Diversity and Infectivity of
      Bacterial Viruses.
AB  - The intestinal microbiota and human health are intimately linked, but
      interactions between bacteria and bacteriophages in the context of the mammalian
      intestine remain largely unexplored. We used comparative population genomics to
      study a tripartite network consisting of a virulent bacteriophage, its bacterial
      host, and a phage-insensitive bacterial strain both in vitro and within the
      murine gut. The bacteriophage adapted to infect the insensitive strain when the
      three partners co-existed in the gut of conventional mice, but not in dixenic
      mice or in planktonic cultures. The molecular changes associated with
      modifications in the bacteriophage host spectrum included single amino acid
      substitutions and an unusual homologous intragenomic recombination event within
      the genome of the bacteriophage. An intermediate bacterial host isolated from the
      murine microbiota mediated bacteriophage adaptation. Our data indicate that by
      offering access to new hosts, the microbiota shifts the genetic diversity of
      bacteriophages, thereby promoting long-term persistence of bacteriophage
      populations.

PMID- 29174402
TI  - Commensal Fungi Recapitulate the Protective Benefits of Intestinal Bacteria.
AB  - Commensal intestinal microbes are collectively beneficial in preventing local
      tissue injury and augmenting systemic antimicrobial immunity. However, given the
      near-exclusive focus on bacterial species in establishing these protective
      benefits, the contributions of other types of commensal microbes remain poorly
      defined. Here, we show that commensal fungi can functionally replace intestinal
      bacteria by conferring protection against injury to mucosal tissues and
      positively calibrating the responsiveness of circulating immune cells.
      Susceptibility to colitis and influenza A virus infection occurring upon
      commensal bacteria eradication is efficiently overturned by mono-colonization
      with either Candida albicans or Saccharomyces cerevisiae. The protective benefits
      of commensal fungi are mediated by mannans, a highly conserved component of
      fungal cell walls, since intestinal stimulation with this moiety alone overrides
      disease susceptibility in mice depleted of commensal bacteria. Thus, commensal
      enteric fungi safeguard local and systemic immunity by providing tonic microbial
      stimulation that can functionally replace intestinal bacteria.

PMID- 29174404
TI  - Does Time to Surgery Affect Outcomes for Periprosthetic Femur Fractures?
AB  - BACKGROUND: Periprosthetic femur fractures around total hip (THA) and total knee
      (TKA) arthroplasties are difficult complications to manage. With native hip
      fractures, delay to fixation has been correlated with an increase in
      postoperative mortality. The effect of time to definitive fixation of
      periprosthetic femur fractures around THA and TKA is not well established. The
      aim of our study is to evaluate the effect of time to definitive fixation on
      postoperative length of stay and mortality for patients with periprosthetic femur
      fractures around THA and TKA. METHODS: A review of 2537 arthroplasty patient
      charts yielded 235 patients who were diagnosed with a periprosthetic femur
      fracture at our institution from 2005 to 2014. Time to surgical management,
      length of stay, demographics, referral status, fracture classification, and
      fixation modality along with mortality was recorded for all patients. RESULTS:
      One hundred eighty patients met study inclusion (111 THAs, 69 TKAs). Average age
      was 79.2 years and 72.2% were female. The average time from admission to
      definitive fixation was 96.5 hours with 31.1% of patients having surgery within
      48 hours after presenting to hospital. Postoperative length of stay and mortality
      were not affected by time to definitive fixation greater than 48 hours for either
      of the periprosthetic TKA or THA patient cohorts. Postoperative mortality within
      1 year was 5.5% for all patients (6.3% THA, 4.3% TKA). CONCLUSION: The timing of
      fixation of periprosthetic femur fractures does not appear to affect
      postoperative length of stay or mortality within 1 year.

PMID- 29174403
TI  - A Bacterial Type III Effector Targets the Master Regulator of Salicylic Acid
      Signaling, NPR1, to Subvert Plant Immunity.
AB  - Most plant bacterial pathogens rely on type III effectors to cause diseases.
      Although it is well known that the plant hormone salicylic acid (SA) plays an
      essential role in defense, whether the master regulator of SA signaling, NPR1, is
      targeted by any plant pathogen effectors is unknown. SA facilitates the reduction
      of cytosolic NPR1 oligomers into monomers, which enter the nucleus and function
      as transcriptional coactivators of plant defense genes. We show that SA promotes
      the interaction between the Pseudomonas syringae type III effector AvrPtoB and
      NPR1. In the presence of SA, AvrPtoB mediates the degradation of NPR1 via the
      host 26S proteasome in a manner dependent on AvrPtoB's E3 ligase activity.
      Intriguingly, we found that NPR1 plays an important role in MAMP-triggered
      immunity (MTI), inducing the expression of MTI marker genes. Thus, this work
      uncovers a strategy in which AvrPtoB targets NPR1 and represses NPR1-dependent SA
      signaling, thereby subverting plant innate immunity.

PMID- 29174405
TI  - Mixing of Head-Stem Components in Total Hip Arthroplasty.
AB  - BACKGROUND: Implant manufacturers proclaim that the tapers of modular total hip
      arthroplasty are not standardized and can vary from manufacturer to manufacturer.
      That is why the combination of various components from different manufacturers
      ("Mix and Match") is not permitted. In this study, different taper combinations
      were investigated experimentally to assess the effect of "Mix and Match"
      regarding the taper connection strength. METHODS: Torque-off tests using hip
      stems and metal femoral heads from 6 different implant manufacturers were
      performed. First the components were tested as intended and afterwards the stems
      were combined with metal heads from other manufacturers. RESULTS: There was no
      significant difference in taper connection strength when stems from the
      manufacturers Link, Smith & Nephew, and Zimmer were combined with heads from
      other manufacturers. The Biomet stems showed a significantly reduced taper
      connection strength if femoral heads of Aesculap, DePuy, or Smith & Nephew were
      used. On the contrary, the DePuy stems in combination with the originally
      intended femoral heads showed a significantly lower taper connection strength
      compared to the use of heads from Link, Biomet, and Zimmer. The same was observed
      for the Aesculap stems in combination with Zimmer heads. CONCLUSION: The results
      of this study suggest that mixing components from different manufacturers may
      affect the taper connection strength and could reduce the stability. As safety
      should be a high priority in patient treatment, any potential risks should be
      avoided. Therefore, mixing and matching of heads and femoral stems from different
      manufacturers cannot be recommended.

PMID- 29174406
TI  - Total Hip Arthroplasty in Patients With Previous Lumbar Fusion Surgery: Are There
      More Dislocations and Revisions?
AB  - BACKGROUND: The purpose of this study was to determine whether the risk of
      dislocation and/or revision following THA is increased in patients with a history
      of prior lumbar fusion given the alterations in dynamic pelvic motion following
      LSF. METHODS: A total of 62,387 patients (5% Medicare part B claims database)
      were identified from 1997 to 2014 with primary THA. From this group, 1809
      patients (2.9%) were stratified to identify those with prior lumbar fusion within
      5 years of primary THA to compare risk of dislocation and revision with those
      without lumbar fusion. Multivariate cox regression analysis was performed
      adjusting for age, socioeconomic status, race, census, region, gender, Charlson
      score, preexisting conditions, and type of fusion. RESULTS: Between years 2002
      and 2014, there was a 293% increase in the number of patients with prior lumbar
      fusion undergoing THA. Prevalence of hip dislocation in patients with lumbar
      fusion before THA was 7.4% compared to 4.8% without fusion, P < .001. There was
      an 80% increase in dislocation in the fusion group at 6 months, 71% at 1 year,
      and 60% at 2 years. There was a 48% increased risk of failure leading to revision
      hip surgery in patients with fusion at 6 months, 41% at 1 year, and 47% at 2
      years. Dislocation was the most common mode of failure leading to revision in
      both the fusion group (20.8%) and the nonfusion group (16%). CONCLUSION: Results
      of this study demonstrate that lumbar fusion before THA is an independent risk
      factor for dislocation leading to increased risk of revision THA.

PMID- 29174407
TI  - Hypothyroidism Increases 90-Day Complications and Costs Following Primary Total
      Knee Arthroplasty.
AB  - BACKGROUND: Thyroid disease is common and often remains undetected in the US
      population. Thyroid hormone has an array of metabolic, immunologic, and
      musculoskeletal functions crucial to well-being. The influence of thyroid disease
      on perioperative outcomes following primary total knee arthroplasty (TKA) is
      poorly understood. We hypothesized that hypothyroidism was associated with a
      higher risk of postoperative complications and 90-day costs following primary
      TKA. METHODS: The Medicare standard analytical files were queried using
      International Classification of Disease codes between 2005 and 2014 to identify
      patients undergoing primary TKA. Patients with a diagnosis of hypothyroidism were
      matched by age and gender on a 1:1 ratio. Ninety-day postoperative complication
      rates, day of surgery, and 90-day global period charges and reimbursements were
      compared between matched cohorts. RESULTS: A total of 2,369,594 primary TKAs were
      identified between 2005 and 2014. After age and gender matching, each cohort
      consisted of 98,555 patients. Hypothyroidism was associated with greater odds of
      postoperative complications compared to matched controls (odds ratio 1.367, 95%
      confidence interval 1.322-1.413). The 90-day incidence of multiple postoperative
      medical and surgical complications, including periprosthetic joint infection, was
      higher among patients with hypothyroidism. Day of surgery and 90-day episode of
      care costs were significantly higher in the hypothyroidism cohort. CONCLUSION:
      This study demonstrated an increased risk of multiple postoperative complications
      and higher costs among patients with hypothyroidism following primary TKA.
      Surgeons should counsel patients on these findings and seek preoperative
      optimization strategies to reduce these risks and lower costs in this patient
      population.

PMID- 29174408
TI  - Survivorship and Outcomes in Patients With Multiple Sclerosis Undergoing Total
      Joint Arthroplasty.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) frequently require total joint
      arthroplasty (TJA). The outcomes of TJA in patients with MS, who are frequently
      on immunomodulatory medications and physically deconditioned, remain largely
      unknown. The aim of this study is to elucidate the survivorship and reasons for
      failure in this patient population. METHODS: A single-institution retrospective
      review of 108 TJAs (46 knees and 62 hips) was performed from 2000 to 2016. An
      electronic chart query based on MS medications and International Classification
      of Diseases, Ninth Revision codes was used to identify this population followed
      by a manual review to confirm the diagnosis. Outcomes were then assessed using
      revision for any reason as the primary end point. Functional outcomes were
      assessed using Short Form 12 scores. Survivorship curves were generated using the
      Kaplan-Meier method. RESULTS: At an average follow-up of 6.2 years, 19.4%
      (21/108) of patients required a revision surgery. Instability (5.6%, P = .0278)
      and periprosthetic joint infection (4.6%, P = .0757) were among the most common
      reasons for revision. The overall survivorship of TJA at years 2, 5, and 7,
      respectively, was 96.5% (95% confidence interval [CI], 92.6-100), 86.3% (95% CI,
      77.7-94.5), and 75.3% (95% CI, 63.5-87.0). Functional score improvement was less
      in MS cohort than patients without MS. CONCLUSION: Patients with MS are at
      increased risk of complications, particularly instability and periprosthetic
      joint infection. Despite this increased risk of complications, patients with MS
      can demonstrate improved functional outcomes, but not as much as patients without
      MS. Patients with MS should be counseled appropriately before undergoing TJA.

PMID- 29174409
TI  - Operating Room Traffic Increases Aerosolized Particles and Compromises the Air
      Quality: A Simulated Study.
AB  - BACKGROUND: Strategies to prevent bacterial fallout and reduce particle count in
      the operating room (OR) are key components of preventing periprosthetic joint
      infection. Although OR traffic control is an important factor, a quantitative
      study has not been performed to investigate the influence of personnel and door
      opening on OR air quality. This simulated study aimed to examine the influence of
      these 2 factors on particle density in OR with and without the laminar air flow
      (LAF). METHODS: Both experiments took place within an empty OR of an arthroplasty
      unit equipped with an LAF system. First, the number of particles in the air was
      counted using a particle counting apparatus while 9 persons entered the room, one
      every 15 minutes. Second, the door was opened and closed starting with zero door
      openings per minute and increasing to 4 in 15-minute increments. Both experiments
      were performed once with the LAF turned on and once without. RESULTS: The number
      of personnel in the OR and the number of door openings per minute correlate with
      the density of particles. Both relationships were significantly reduced by
      turning the LAF on (correlation coefficients <0.4). With the LAF being turned on,
      the particle density per person decreased from 211.19 to 18.19 particles/ft3 (P <
      .001) and the particle density per rate of door openings declined from 117.80 to
      1.90 particles/ft3 (P = .017). CONCLUSION: This study confirms that personnel and
      door opening are a major source of particles in the OR air. Controlling traffic
      is critical for reduction of particles and is likely to be a key preventative
      strategy in reducing periprosthetic joint infection. LAF is protective against
      the negative influence of number of people and door openings.

PMID- 29174410
TI  - A government policy on full-time nursing employment in Ontario, Canada: An
      evaluation.
AB  - PURPOSE: To evaluate the impact of a government full-time employment policy
      targeting new graduate nurses in the province of Ontario, Canada, by comparing
      participants with non-participants. METHODS: The Policy Impact on Nurse
      Employment (PINEP) survey was administered in 2014 to nurses who graduated
      between 2007 and 2012. Backward multiple logistic regression analysis was
      conducted to determine the effect of participation in the policy on key outcomes:
      full-time employment, retention and perceptions of clinical proficiency. RESULTS:
      A total of 2369 nurses responded to the survey. Policy participants were 1.5
      times more likely to be employed full-time and 2.3 times more likely to be
      retained in their initial position at the time of survey compared to non
      participants. Participants also perceived their clinical proficiency to be
      higher. CONCLUSIONS: The evidence is converging around the importance of
      providing full-time employment to nurses to sustain the workforce, increase
      clinical proficiency and improve patient outcomes. In Ontario, the government
      created a policy to stimulate full-time employment for nurses. Results
      demonstrate that nursing employment has become more stable. Yet more needs to be
      done particularly in relation to the precarious employment trend.

PMID- 29174412
TI  - How do we manage overdiagnosis/overtreatment in breast screening?
AB  - Overdiagnosis is the inevitable flip side of early detection resulting in
      unnecessary labelling of well women with a diagnosis of cancer and possible
      unnecessary treatment. Overdiagnosis occurs because breast cancers have different
      rates of growth and slow-growing cancers are preferentially detected by
      screening. Some of these slow-growing screen-detected cancers may never have been
      clinically apparent during an individual's lifetime. Evaluating the benefits and
      risks of screening are complex, but this has been performed for the UK population
      by an independent review led by Professor Marmot. It might be possible to limit
      overdiagnosis by identifying women with "low-risk disease" earlier, either at the
      point of screening when additional investigations could be delayed (possibly for
      ever) so that they are not subjected to additional diagnostic tests, or at the
      point of diagnosis. Both these options would require major re-education of
      clinicians and the public who would need to accept that screening is
      "deliberately ignoring a cancer". There is a long surgical history of reducing
      the burden of treatment, which continues today with trials of management of the
      axilla and reducing or even omitting radiotherapy for low-risk disease. The Low
      Risk Ductal Carcinoma In Situ trial (LORIS) has started to identify a group of
      breast cancer patients who could avoid surgery and be offered active monitoring.
      We need to consider planning a similar trial for low-risk invasive breast cancer.

PMID- 29174414
TI  - Introduction to special issue: Body mass estimation - Methodological issues and
      fossil applications.

PMID- 29174413
TI  - MRI-measured myocardial iron load in patients with severe diabetic heart failure.
AB  - AIM: To investigate whether a correlation exists between abnormal myocardial iron
      status and cardiac lipid deposition as well as other biomarkers in patients with
      diabetic heart failure (DHF). MATERIALS AND METHODS: Seventeen volunteers (Group
      1), 26 patients with non-severe DHF (Group 2), and 25 patients with severe DHF
      (Group 3) were recruited for this study. Myocardial middle-section T2* mapping
      and septal 1H magnetic resonance spectroscopy (1H-MRS) were performed using a 3 T
      magnetic resonance imaging (MRI) machine to assess the iron status and lipid
      deposition individually. Fasting venous blood was used to examine serum
      biomarkers. RESULTS: Cardiac T2* (ms) of the three groups were 22.8+/-2.1, 21.7+/
      1.8, and 18.6+/-1.3, respectively. The value of Group 3 was significantly lower
      than that of the other two groups (p<0.001). Myocardial triglyceride (%) levels
      differed among the three groups (Group 1, 0.53+/-0.13; Group 2, 1.11+/-0.29;
      Group 3, 1.47+/-0.12; p<0.001). Cardiac T2* was inversely correlated with both
      cardiac triglycerides and left ventricular ejection fraction (LVEF) in overall
      participants (Groups 1-3) or Group 3 (each p<0.001). CONCLUSIONS: Abnormal
      myocardial iron status was found in patients with severe diabetic heart failure.
      Myocardial lipotoxicity may be responsible for this process.

PMID- 29174411
TI  - Gestational intermittent hypoxia increases susceptibility to neuroinflammation
      and alters respiratory motor control in neonatal rats.
AB  - Sleep disordered breathing (SDB) and obstructive sleep apnea (OSA) during
      pregnancy are growing health concerns because these conditions are associated
      with adverse outcomes for newborn infants. SDB/OSA during pregnancy exposes the
      mother and the fetus to intermittent hypoxia. Direct exposure of adults and
      neonates to IH causes neuroinflammation and neuronal apoptosis, and exposure to
      IH during gestation (GIH) causes long-term deficits in offspring respiratory
      function. However, the role of neuroinflammation in CNS respiratory control
      centers of GIH offspring has not been investigated. Thus, the goal of this hybrid
      review/research article is to comprehensively review the available literature
      both in humans and experimental rodent models of SDB in order to highlight key
      gaps in knowledge. To begin to address some of these gaps, we also include data
      demonstrating the consequences of GIH on respiratory rhythm generation and
      neuroinflammation in CNS respiratory control regions. Pregnant rats were exposed
      to daily intermittent hypoxia during gestation (G10-G21). Neuroinflammation in
      brainstem and cervical spinal cord was evaluated in P0-P3 pups that were injected
      with saline or lipopolysaccharide (LPS; 0.1mg/kg, 3h). In CNS respiratory control
      centers, we found that GIH attenuated the normal CNS immune response to LPS
      challenge in a gene-, sex-, and CNS region-specific manner. GIH also altered
      normal respiratory motor responses to LPS in newborn offspring brainstem-spinal
      cord preparations. These data underscore the need for further study of the long
      term consequences of maternal SDB on the relationship between inflammation and
      the respiratory control system, in both neonatal and adult offspring.

PMID- 29174415
TI  - Neuroinflammation induced by amyloid beta25-35 modifies mucin-type O
      glycosylation in the rat's hippocampus.
AB  - Amyloid-beta (Abeta) plays a relevant role in the neurodegenerative process of
      Alzheimer's disease (AD). The 25-35 peptide of amyloid-beta (Abeta25-35) induces
      the inflammatory response in brain experimental models. Mucin-type O
      glycosylation has been associated with inflammation of brain tissues in AD, thus
      in this work, we aimed at identifying changes in the glycosylation profile
      generated by the injection of Abeta25-35 into the CA1 of the hippocampus of rats,
      using histochemistry with lectins. Our results indicate that 100MUM Abeta25-35
      induce increased recognition of the Amaranthus leucocarpus lectin (ALL) (specific
      for Galbeta1,3-GalNAcalpha1,0-Ser/Thr); whereas concanavalin A (Con A) (specific
      for alpha-Man) showed no differences among treated and control groups of rats.
      Jacalin and peanut agglutinin (Galbeta1,3GalNAcalpha1,0-Ser/Thr) showed no
      recognition of brain cells of control or treated rats. After 6-h treatment of the
      tissue with trypsin or with 200mM GalNAc, the interaction with ALL was inhibited.
      Immunohistochemistry showed positive anti-NeuN and ALL-recognition of neurons;
      however, anti-GFAP and anti-CD11b showed no co-localization with ALL. The ALL+
      neurons revealed the presence of cytochrome C in the cytosol and active caspase 3
      in the cytosol and nucleus. Administration of the interleukin-1 receptor
      antagonist (IL-1RA) to Abeta25-35-treated rats diminished neuroinflammation and
      ALL recognition. These results suggest a close relationship among over-expression
      of mucin-type O-glycosylation, the neuroinflammatory process, and neuronal death.

PMID- 29174416
TI  - Unrelated donor umbilical cord blood transplant versus unrelated hematopoietic
      stem cell transplant in patients with acute leukemia: A meta-analysis and
      systematic review.
AB  - Acute leukemia is a global disease with a poor prognosis for many patients. While
      an increasing number of patients with acute leukemia are being treated with
      unrelated hematopoietic stem cell transplants (HSCT) or umbilical cord blood
      transplants (UCBT), recent comparative reports of these 2 procedures are lacking.
      Therefore, we conducted a meta-analysis of the safety and efficacy of unrelated
      HSCT and unrelated single-unit UCBT for the treatment of pediatric and adult
      patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).
      The primary outcomes were the rates of relapse, overall survival (OS),
      progression-free survival (PFS), and days to neutrophil and platelet recovery.
      Pooled effects (odds ratios [OR] or difference in means) were determined with
      either random- or fixed-effects models. Our meta-analysis included 9 studies that
      enrolled 6762 patients (UCBT: n=2026; HSCT: n=4736). The risk of relapse for
      patients undergoing UCBT was similar to that of patients who received an HSCT
      (OR=1.030; 95%CI, 0.767 to 1.383, P=0.847). We also found no difference between
      HSCT and UCBT for OS (pooled OR=1.417; 95%CI, 0.936 to 2.146; P=0.100) or PFS
      (OR=1.165; 95%CI, 0.996 to 1.362; P=0.056). However, neutrophil and platelet
      recovery periods were both shorter after HSCT than after UCBT (neutrophil
      recovery: difference in means=-3.420, 95% CI: -5.491 to -1.349, P=0.001; platelet
      recovery: difference in means -20.350, 95% CI: -33.656 to -7.044, P=0.003).
      Collectively, our data provide strong evidence to support increased use of cord
      blood transplants for both adults and children with acute leukemia.

PMID- 29174417
TI  - Phenylpropanoids isolated from Piper sarmentosum Roxb. induce apoptosis in breast
      cancer cells through reactive oxygen species and mitochondrial-dependent
      pathways.
AB  - The aim of the present study is to isolate bioactive compounds from the roots of
      Piper sarmentosum and examine the mechanism of action using human breast cancer
      cell line (MDA-MB-231). Bioassay guided-fractionation of methanolic extract led
      to the isolation of asaricin (1) and isoasarone (2). Asaricin (1) and isoasarone
      (2) had significant cytotoxicity towards MDA-MB-231. MCF-10A (human normal breast
      epithelial cells) cells are less sensitive than MDA-MB-231, but they respond to
      the treatment with the same unit of measurement. Both compounds increase reactive
      oxygen species (ROS), decrease mitochondrial membrane potential (MMP) and enhance
      cytochrome c release in treated MDA-MB-231 cells. Isoasarone (2) markedly
      elevated caspase -8 and -3/7 activities and caused a decline in nuclear NF-kappaB
      translocation, suggesting extrinsic, death receptor-linked apoptosis pathway.
      Quantitative PCR results of MDA-MB-231 treated with asaricin (1) and isoasarone
      (2) showed altered expression of Bcl-2: Bax level. The inhibitory potency of
      these isolates may support the therapeutic uses of these compounds in breast
      cancer.

PMID- 29174418
TI  - Responses of human ankle muscles to mediolateral balance perturbations during
      walking.
AB  - During walking our balance is maintained by muscle action. In part these muscle
      actions automatically respond to the imbalance. This paper considers responses to
      balance perturbations in muscles around the ankle, peroneus longus (PL), tibialis
      anterior (TA) and soleus (SO). It is investigated if their action is related to
      previously observed balance mechanisms: the 'braking reaction' and the
      mediolateral ankle strategy. Subjects walked on a treadmill and received pushes
      to the left and pulls to the right in various phases of the gait cycle. Muscle
      actions were divided into medium latency R1 (100-150 ms), long latency R2 (170
      250 ms), and late action R3 (270-350 ms). Short latency responses, before 100 ms,
      were not observed but later responses were prominent. With inward perturbations
      (e.g. pushes to the left shortly before or during stance of the right foot)
      responses in RPL were seen. The forward roll-over of the CoP was briefly stalled
      in mid stance, so that the heel was not lifted. Stance was shortened. With
      outward perturbations, pushes to the left shortly before or during stance of the
      left foot, responses in all three muscles, LTA, LSO, and LPL were seen. Our
      interpretation is that these muscle activations induce a 'braking reaction' but
      could also contribute to the 'mediolateral ankle strategy'. The resultant balance
      correction is small but fast, and so diminishes the need for later corrections by
      the stepping strategy.

PMID- 29174419
TI  - Co-infection with influenza-associated acute respiratory distress syndrome
      requiring extracorporeal membrane oxygenation.
AB  - The co-infection frequency and impact among influenza-associated acute
      respiratory distress syndrome (ARDS) patients requiring extracorporeal membrane
      oxygenation (ECMO) are not known. This retrospective observational analysis
      concerned data prospectively collected from patients admitted to our medical
      intensive care unit (ICU) who received ECMO support for influenza-associated ARDS
      between 2009-2016. Co-infection was defined as occurring within 48 h following
      ICU admission. Among the 77 ARDS patients requiring ECMO support, 39 (51%)
      developed co-infections, with Staphylococcus aureus [18 (46%) of the co-infected
      patients] being the most prevalent pathogen. Panton-Valentin leukocidin (PVL)
      producing S. aureus was isolated from 10 patients (56% of S. aureus co-infections
      and 26% of all co-infections). Co-infected patients were comparable with those
      without co-infection, except for BMI, initial disease severity and antibiotic
      treatment prior to admission. Co-infection was associated with higher in-ICU
      mortality (62% vs. 29%; P = 0.006) and with fewer ECMO-free days [median (IQR) 0
      (0-19) vs. 23 (0-46); P = 0.004] and fewer mechanical ventilation-free days [0 (0
      0) vs. 6 (0-35); P = 0.003] on Day 60. Multivariable analysis retained age >49
      years, pre-ECMO Simplified Acute Physiology Score (SAPS) II score >70 and co
      infection as independent predictors of hospital mortality. In conclusion, co
      infection is frequent in ECMO-treated patients with influenza-associated ARDS,
      affecting ca. 50%, and is independently associated with poor outcome.
      Staphylococcus aureus was the most frequently identified pathogen, with a high
      rate of PVL-positive S. aureus. Whether specific therapy targeting PVL-producing
      S. aureus should be given remains to be determined.

PMID- 29174421
TI  - Morphological changes of vertebral compression fracture with intra-vertebral
      cleft treated with percutaneous vertebroplasty.
AB  - BACKGROUND: Vertebroplasty represents an established treatment option for
      osteoporotic vertebral compression fracture (OVCF), but its radiographic and
      clinical outcomes have not been clearly described in patients with intra
      vertebral cleft (IVC). The aim of this study was to assess vertebral height
      restoration, recollapse and change of back pain in OVCF patients with or without
      IVC. METHODS: The records of 108 patients with IVC (group I) and 233 patients
      without IVC (group II) were included in our analysis between March 2001 and
      February 2014. The heights of the anterior, middle, and posterior columns, as
      well as the wedge angle (WA) of the fractured vertebral body were measured. For
      each vertebral column, the mean height of the superior and inferior vertebral
      body served as reference. Pre-operative, postoperative, and final compression
      rates (CR), as well as restoration and recollapse rates were calculated for each
      column. Subjective back pain was assessed as the numeric rating scale (NRS)
      score. RESULTS: The overall incidence of IVC in OVCF patients who underwent
      vertebroplasty was 20.8% (127/611 patients). Group I showed significantly higher
      CR over the entire follow-up period, with the exception of CR for the anterior
      column at final follow-up, and CR for the posterior column throughout the follow
      up. The mean restoration rates at the anterior and middle column immediately
      after vertebroplasty were also significantly larger in group I. Recollapse rate
      in all columns was similar for groups I and II. The mean wedge angle was
      significantly larger in group I over the entire follow-up period. The groups did
      not differ in terms of NRS score at final follow-up. CONCLUSIONS: Vertebroplasty
      restores vertebral body heights and WA more effectively in OVCF patients with
      IVC, and provides satisfactory radiographic and clinical outcomes regardless of
      the presence of IVC.

PMID- 29174420
TI  - Panton-Valentine leukocidin-positive Staphylococcus aureus: a position statement
      from the International Society of Chemotherapy.

PMID- 29174422
TI  - Bioabsorbable magnesium versus standard titanium compression screws for fixation
      of distal metatarsal osteotomies - 3 year results of a randomized clinical trial.
AB  - BACKGROUND: For the treatment of hallux valgus commonly distal metatarsal
      osteotomies are performed. Persistent problems due to the hardware and the
      necessity of hardware removal has led to the development of absorbable implants.
      To overcome the limitations of formerly used materials for biodegradable
      implants, recently magnesium has been introduced as a novel implant material.
      This is the first study showing mid-term clinical and radiological (MRI) data
      after using magnesium implants for fixation of distal metatarsal osteotomies.
      MATERIAL AND METHODS: 26 patients with symptomatic hallux valgus were included in
      the study. They were randomly selected to be treated with a magnesium or standard
      titanium screw for fixation of a modified distal metatarsal osteotomy. The
      patients had a standardized clinical follow up and MRI investigation 3 years'
      post-surgery. The clinical tests included the range of motion of the MTP 1, the
      AOFAS, FAAM and SF-36 scores. Further on the pain was evaluated on a VAS.
      RESULTS: Eight patients of the magnesium group and 6 of the titanium group had a
      full clinical and MRI follow up 3 years postoperatively. One patient was lost to
      follow-up. All other patients could be interviewed, but denied full study
      participation. There was a significant improvement for all tested clinical scores
      (AOFAS, SF-36, FAAM, Pain-NRS) from pre-to postoperative investigation, but no
      statistically relevant difference between the groups. Magnesium implants showed
      significantly less artifacts in the MRI, no implant related cysts were found and
      the implant was under degradation three years postoperatively. CONCLUSION: In
      this study, bioabsorbable magnesium implants showed comparable clinical results
      to titanium standard implants 3 years after distal modified metatarsal osteotomy
      and were more suitable for radiologic analysis. LEVEL OF EVIDENCE: 2.

PMID- 29174423
TI  - Posterior spinal fusion for scoliosis after Fontan procedure: A case series.
AB  - BACKGROUND: As the surgical treatment of scoliosis after a Fontan procedure is
      very challenging due to the risk of various perioperative complications, case
      reports are scarce. We herein describe three patients who were successfully
      treated for scoliosis following a Fontan procedure and discuss their clinical and
      radiological outcomes. METHODS: We retrospectively reviewed three cases of
      scoliosis treated by posterior spinal fusion after a Fontan procedure. RESULTS:
      Mean preoperative major curve Cobb angle was 83.7 degrees , mean surgical time
      was 233.0 min, and mean blood loss was 1167 g. The mean correction rate of the
      major curve was 48.0%. Surgical outcome as evaluated by Scoliosis Research
      Society-22 patient questionnaires revealed acceptable results without any severe
      complications. CONCLUSIONS: Corrective surgery for scoliosis after a Fontan
      procedure becomes a stronger option if cardiac insufficiency is prevented during
      the perioperative period and a conservative plan is carried out with minimal
      invasiveness and operation time.

PMID- 29174424
TI  - Hemi-arthroplasty performed in a 109-year-old patient with intertrochanteric
      fracture: A case report.
AB  - The mortality of conservative treatment and the risk resulting from operation for
      elderly patients with femoral intertrochanteric fractures are high. Safety in the
      perioperative period and quicker recovery should be placed at the top priority
      for elderly patients with hip fractures. We reported a case of 109-year-old
      female patient with intertrochanteric fracture who has undergone the
      hemiarthroplasty in our center recently. With sciatic nerve and lateral cutaneous
      nerve block anesthesia, she was offered the artificial femoral head replacement
      in the lumbar plexus block after sufficient preoperative preparation. The surgery
      went well with minimally invasive cut, and the patient's recovery was
      satisfactory.

PMID- 29174425
TI  - Physiological response of a red tide alga (Skeletonema costatum) to nitrate
      enrichment, with special reference to inorganic carbon acquisition.
AB  - A classical red tide alga Skeletonema costatum was cultured under various nitrate
      levels to investigate its physiological response to nitrate enrichment combined
      with CO2 limitation. The higher nitrate levels increased content of
      photosynthetic pigments (Chl a and Chl c), electron transport rate in photosystem
      II, photosynthetic O2 evolution, and thus growth rate in S. costatum. On the
      other hand, the lower CO2 levels (3.5-4.4 MUmol kg-1 seawater) and higher pH
      (8.56-8.63) values in seawater were observed under higher nitrate conditions.
      Redox activity of plasma membrane and carbonic anhydrase in S. costatum was
      enhanced to address the reduced CO2 level at higher nitrate levels. In addition,
      the pH compensation point was enhanced and direct HCO3- use was induced at higher
      nitrate levels. These findings indicate that nitrate enrichment would stimulate
      the breakout of S. costatum dominated red tides via enhancing its photosynthetic
      performances, and maintain a quick growth rate under CO2 limitation conditions
      through improving its inorganic carbon acquisition capability. Our study sheds
      light on the mechanisms of S. costatum defeating CO2 limitation during algal
      bloom.

PMID- 29174426
TI  - Corrigendum to "Evaluation of in vivo and in vitro toxicological and genotoxic
      potential of aluminum chloride" [Chemosphere 175 (2017), 130-137].

PMID- 29174427
TI  - The serum leptin level in non-obese patients with obstructive sleep apnea.
AB  - OBJECTIVE: This study aimed to determine the association between the severity of
      obstructive sleep apnea (OSA) and the serum leptin level in non-obese OSA
      patients. METHODS: This prospective case-control study included non-obese OSA
      patients that presented with sleep-related disturbances and underwent
      polysomnography (PSG) between April 2015 and June 2016. The serum leptin level
      was measured and its relationship to PSG parameters was investigated. RESULTS:
      The study included 73 OSA patients (20 female and 53 male) with a mean age of
      41.1+/-11.5 years and mean body-mass index (BMI) of 26.4+/-2.7kgm-2. The serum
      leptin level in 44 patients with moderate/severe OSA (AHI >=15) was 3.4+/-2.6ngmL
      1, versus 4.5+/-3.8ngmL-1 in 29 patients with snoring/mild OSA (AHI <15)
      (P=0.20). There were not any correlations between any of the PSG parameters and
      the serum leptin level, but there was a significant correlation between the
      leptin level and BMI (r=0.345, P<0.01). CONCLUSION: The serum leptin level does
      not differ significantly between non-obese OSA patients with moderate/severe and
      snoring/mild OSA. Obesity is the primary factor associated with the serum leptin
      level.

PMID- 29174428
TI  - Radiation Dose, Local Disease Progression, and Overall Survival in Patients With
      Inoperable Non-Small Cell Lung Cancer After Concurrent Chemoradiation Therapy.
AB  - PURPOSE: To identify predictors of local control and overall survival (OS) for
      patients with inoperable non-small cell lung cancer treated with concurrent
      chemoradiation therapy. METHODS AND MATERIALS: We identified 491 patients with
      newly diagnosed stage IIIA-IIIB non-small cell lung cancer who had received 60 to
      74 Gy (with concurrent chemotherapy) from January 2005 through December 2013 and
      grouped them by radiation dose received: 60 to 63 Gy, 64 to 66 Gy, 67 to 70 Gy,
      or 71 to 74 Gy. Local progression (LP) was that appearing within the high-dose
      volume (planning target volume plus 1-cm margin). Times to events were calculated
      from the completion of radiation therapy. Potential predictors of LP and OS were
      analyzed with a Cox regression model. RESULTS: Rates of LP for all patients were
      16.2% at 1 year, 26.2% at 2 years, 31.0% at 3 years, 32.9% at 4 years, and 32.9%
      at 5 years; corresponding OS rates were 85.3%, 61.2%, 44.5%, 37.0%, and 31.6%.
      Median OS time was 21 months (range, 2.9-99.9 months). In multivariate analysis,
      receipt of 67 to 70 Gy was associated with improved LP-free survival (LPFS)
      relative to 60 to 63 Gy (hazard ratio [HR] 1.83, 95% confidence interval [CI]
      1.062-3.150, P=.030) or 64 to 66 Gy (HR 2.14, 95% CI 1.159-3.969, P=.015). Non
      squamous histology (HR 0.23, 95% CI 0.114-0.478, P=.000), gross tumor volume (HR
      1.00, 95% CI 1.000-1.003, P=.018) and induction chemotherapy (HR 1.86, 95% CI
      1.239-2.778, P=.003) were independent predictors of LPFS. Local progression-free
      survival was the only independent predictor of OS (HR 2.71, 95% CI 1.331-5.512,
      P=.006). Incidence of grade >=3 radiation pneumonitis was no different among dose
      groups (P=.307). CONCLUSIONS: Squamous histology, large tumor volumes, and
      receipt of induction chemotherapy all predicted worse LPFS. Doses of 67 to 70 Gy
      were associated with improved LP-free survival after chemoradiotherapy. The link
      between LP and reduced OS suggests that more effective local control strategies
      are warranted.

PMID- 29174430
TI  - The expanding role of innate lymphoid cells and their T-cell counterparts in
      gastrointestinal cancers.
AB  - Innate lymphoid cells (ILCs) contribute to the regulation of gastrointestinal
      (GI) homeostasis. Over the past 15 years, there has been a large effort to
      dissect the mechanisms required for GI homeostasis, with a major focus on
      different immune cell populations and the cytokines that they produce. In
      contrast to T-helper (Th) cells, ILCs respond rapidly to cytokines in their
      microenvironment in the absence of specific antigens; however, once activated
      both cell populations have similar effector functions. Two effector cytokines
      produced by both ILC3 and Th17 cell populations, Interleukin (IL)-17 and IL-22,
      have taken center stage for their ability to signal directly to GI epithelial
      cells and promote epithelial cell survival. In this review, we outline our
      current understanding of ILCs in the GI tract, and focus on GI cancers associated
      with aberrant production of IL-17 and IL-22. We highlight evidence from both
      mouse and patient-based analyses and discuss how tumor cells may hijack the
      potential evolutionary redundancy of these two cell populations.

PMID- 29174429
TI  - Evaluating the evidence for non-monotonic dose-response relationships: A
      systematic literature review and (re-)analysis of in vivo toxicity data in the
      area of food safety.
AB  - This study aims to evaluate the evidence for the existence of non-monotonic dose
      responses (NMDRs) of substances in the area of food safety. This review was
      performed following the systematic review methodology with the aim to identify in
      vivo studies published between January 2002 and February 2015 containing evidence
      for potential NMDRs. Inclusion and reliability criteria were defined and used to
      select relevant and reliable studies. A set of six checkpoints was developed to
      establish the likelihood that the data retrieved contained evidence for NMDR. In
      this review, 49 in vivo studies were identified as relevant and reliable, of
      which 42 were used for dose-response analysis. These studies contained 179 in
      vivo dose-response datasets with at least five dose groups (and a control group)
      as fewer doses cannot provide evidence for NMDR. These datasets were extracted
      and analyzed using the PROAST software package. The resulting dose-response
      relationships were evaluated for possible evidence of NMDRs by applying the six
      checkpoints. In total, 10 out of the 179 in vivo datasets fulfilled all six
      checkpoints. While these datasets could be considered as providing evidence for
      NMDR, replicated studies would still be needed to check if the results can be
      reproduced to rule out that the non-monotonicity was caused by incidental
      anomalies in that specific study. This approach, combining a systematic review
      with a set of checkpoints, is new and appears useful for future evaluations of
      the dose response datasets regarding evidence of non-monotonicity.

PMID- 29174431
TI  - Pediatric thyroid cancer patients referred to high-volume facilities have
      improved short-term outcomes.
AB  - BACKGROUND: Thyroid cancer is the most common endocrine malignancy in children,
      albeit still rare. This study sought to measure the association between outcomes
      and case volume of the treatment facility for pediatric patients with thyroid
      cancer. METHODS: The National Cancer Data Base (1998-2011) was queried for all
      pediatric patients (age <= 18 years) with thyroid cancer. Demographic, clinical,
      and pathologic features were evaluated for all patients. Case volume of the
      treating facility was defined as the number of pediatric thyroid cancer patients
      at that facility during the study period. Restricted cubic spline modeling was
      used to determine a volume threshold associated with decreased risk of 30-day
      readmission. Patients were assigned to volume groups based on this threshold.
      Logistic regression was utilized to estimate the effect of volume on 30-day
      readmission. RESULTS: In total, 4,466 patients met inclusion criteria. The
      majority were girls (79.1%), white (86.1%), and underwent total thyroidectomy
      (86.9%). Compared with patients treated at the low-volume facilities, those
      treated at the high-volume facilities were more likely to have medullary thyroid
      cancer (10.7% versus 3.7%) and undergo total thyroidectomy (90.8% versus 86.3%)
      (all P < .01). After adjustment, treatment at low-volume facilities was
      associated with an increased likelihood of readmission after operative treatment
      (odds ratio = 3.52, P = .01). CONCLUSION: Pediatric patients with thyroid cancer
      treated at low-volume facilities are more likely to be readmitted after thyroid
      surgery than patients treated at high-volume facilities. Providers should
      consider the case volume status at the treating facility when referring these
      children for thyroid surgery.

PMID- 29174432
TI  - Primary aldosteronism: making sense of partial data sets from failed adrenal
      venous sampling-suppression of adrenal aldosterone production can be used in
      clinical decision making.
AB  - BACKGROUND: It has been suggested that accurate clinical decisions may be made in
      patients with primary aldosteronism (PA) in the setting of failed cannulation of
      an adrenal vein, thereby utilizing only data from either right or left adrenal
      venous sampling (AVS) alone. METHODS: Retrospective analysis was performed for
      all patients with PA who underwent successful bilateral AVS. Adrenal
      vein/inferior vena cava index (AV/IVC index) was calculated by dividing
      aldosterone/cortisol ratio of the adrenal vein by aldosterone/cortisol ratio in
      the inferior vena cava, as described in a previously published study. We examined
      the rates of inappropriate adrenalectomy and failure to recognize unilateral
      disease when previously published cutoffs are used. RESULTS: Inclusion criteria
      were met in 150 patients; 61 with bilateral and 89 with unilateral disease.
      AV/IVC index cutoff of <=0.5 to predict contralateral disease would have not led
      to any inappropriate adrenalectomies and would have missed 19% of patients with
      unilateral disease; AV/IVC index cutoff of >=5.5 to predict ipsilateral
      unilateral disease would have resulted in inappropriate adrenalectomy in 18% of
      patients (95% CI 8-34%, P < .01) and would have not recognized 55% of patients
      with unilateral disease (P < .01). CONCLUSION: The cortisol-corrected adrenal
      vein/inferior vena cava aldosterone index with a cutoff value of <=0.5 performed
      well in identifying patients with contralateral unilateral disease. AV/IVC index
      of >=5.5 cannot be used to reliably diagnose ipsilateral unilateral disease
      because 18% of patients undergoing adrenalectomy based on this cutoff would have
      bilateral disease.

PMID- 29174433
TI  - Novel chimeric parapoxvirus CF189 as an oncolytic immunotherapy in triple
      negative breast cancer.
AB  - BACKGROUND: Triple-negative breast cancer is an aggressive subtype of breast
      cancer with high recurrence rate and poor prognosis. Here we describe a novel,
      genetically engineered parapoxvirus that efficiently kills triple-negative breast
      cancer. METHODS: A novel chimeric parapoxvirus (CF189) was generated via
      homologous recombination and identified through high-throughput screening.
      Cytotoxicity was assayed in vitro in 4 triple-negative breast cancer cell lines.
      Viral replication was examined through standard plaque assay. Orthotopic triple
      negative breast cancer xenografts were generated by MDA-MB-468 implantation into
      the 2nd and 4th mammary fat pads of athymic nude mice and treated with the virus.
      RESULTS: Chimeric parapoxvirus (CF189) demonstrated dose-dependent cytotoxicity
      at low multiplicity of infection, with > 80% cell death 6 days after treatment.
      Significant reductions in tumor size were observed 2 weeks after intratumoral
      injection at doses as low as 103 plaque-forming units (PFU) compared with control
      (P < 0.01). In addition, abscopal effect (shrinkage of noninjected remote tumors)
      was clearly demonstrated. CONCLUSION: Chimeric parapoxvirus (CF189) demonstrated
      efficient cytotoxicity in vitro and potent antitumor effect in vivo at doses as
      low as 103 PFU. These are data encouraging of clinical development for this
      highly potent agent against triple-negative breast cancer.

PMID- 29174434
TI  - Incidence and impact of adverse drug events contributing to hospital readmissions
      in kidney transplant recipients.
AB  - BACKGROUND: The incidence and impact of adverse drug events (ADEs) leading to
      hospitalization and as a predominant risk factor for late graft loss has not been
      studied in transplantation. METHODS: This was a longitudinal cohort study of
      adult kidney recipients transplanted between 2005 and 2010 and followed through
      2013. There were 3 cohorts: no readmissions, readmissions not due to an adverse
      drug event, and adverse drug events contributing to readmissions. The rationale
      of the adverse drug events contribution to the readmission was categorized in
      terms of probability, preventability, and severity. RESULTS: A total of 837
      patients with 963 hospital readmissions were included; 47.9% had at least one
      hospital readmission and 65.0% of readmissions were deemed as having an ADE
      contribute. The predominant causes of readmissions related to ADEs included non
      opportunistic infections (39.6%), opportunistic infections (10.5%), rejection
      (18.1%), and acute kidney injury (11.8%). Over time, readmissions due to under
      immunosuppression (rejection) significantly decreased (-1.6% per year), while
      those due to over-immunosuppression (infection, cancer, or cytopenias)
      significantly increased (2.1% increase per year [difference 3.7%, P = .026]).
      Delayed graft function, rejection, creatinine, graft loss, and death were all
      significantly greater in those with an ADE that contributed to a readmission
      compared the other two cohorts (P < .05). CONCLUSION: These results demonstrate
      that ADEs may be associated with a significant increase in the risk of hospital
      readmission after kidney transplant and subsequent graft loss.

PMID- 29174435
TI  - Dopamine in high-risk populations: A comparison of subjects with 22q11.2 deletion
      syndrome and subjects at ultra high-risk for psychosis.
AB  - Striatal dopamine (DA) dysfunction has been consistently reported in psychotic
      disorders. Differences and similarities in the pathogenesis between populations
      at clinical and genetic risk for developing psychosis are yet to be established.
      Here we explored markers of dopamine (DA) function in subjects meeting clinically
      ultra-high risk criteria for psychosis (UHR) and in subjects with 22q11.2
      deletion syndrome (22q11DS), a genetic condition associated with significant risk
      for developing psychotic disorders. Single Photon Emission Computed Tomography
      (SPECT) with 123I-labelled iodobenzamide ([123I]IBZM) was used to measure
      striatal DA D2/3 receptor binding potential (D2R BPND). Also, peripheral DAergic
      markers were assessed in serum and urine (plasma prolactin (pPRL), plasma
      homovanillic acid (pHVA) and urine DA(uDA)). No significant difference in
      striatal D2R BPND was found between UHR and 22q11DS subjects. Compared to UHR
      subjects, pPRL and pHVA were lower and uDA levels were higher in the 22q11DS
      subjects. However, after correcting for age and gender, only pPRL as
      significantly lower in the 22q11DS patients. These results may suggest that there
      are differences in DAergic markers between subjects with UHR and with 22q11DS
      that may reflect differences in the pathways to psychosis. However, bigger
      samples are needed to replicate these findings.

PMID- 29174436
TI  - Reduced frontal grey matter, life history of aggression, and underlying genetic
      influence.
AB  - Physically healthy, adult, same-sexed twins (n = 287) from a population-based
      twin cohort underwent high-resolution magnetic resonance imaging (MRI) to
      identify fronto-limbic brain regions significantly associated with lifetime
      history of aggression. MRI scans used a 3D magnetization-prepared rapid
      acquisition gradient-echo (MP-RAGE) sequence, for voxel-based morphometry (VBM)
      and history of aggressive behavior was assessed using the Life History of
      Aggression measure. Aggression had modest, inverse associations with grey matter
      volume (GMV) in medial prefrontal cortex (mPFC, b = -0.20, se = 0.05, p < 0.001)
      and lateral prefrontal cortex (lPFC, b = -0.23, se = 0.06, p < 0.001). These
      associations were not confounded by other demographic, psychiatric, or
      personality factors. Biometrical twin analyses revealed significant
      heritabilities of 0.57 for GMV in the mPFC cluster and 0.36 for GMV in the lPFC
      cluster. Genetic factors accounted for the majority of the phenotypic
      correlations between aggression and mPFC GMV (85.3%) and between aggression and
      lPFC GMV (63.7%). Reduced GMV of prefrontal brain regions may be a neuronal
      characteristic of individuals with substantial histories of aggressive behavior
      regardless of psychiatric diagnosis. As such, these data suggest an anatomical
      correlate, with a possible genetic etiology, associated with functional deficits
      in social-emotional information processing.

PMID- 29174437
TI  - Neural simulation mechanisms and social-emotional function in schizophrenia.
AB  - Impairment in simulation, i.e., the generation of internal representations of
      experiences, may contribute to social dysfunction in schizophrenia spectrum
      disorders (SZ). Using a novel fMRI task, we identified neural representations
      generated during simulation of sensorimotor experiences and evaluated their
      associations with socioemotional function in 19 individuals with SZ and 24
      psychiatrically-healthy controls (HC). Participants watched videos depicting a
      painful sensorimotor experience in the hand or foot of another person and were
      then asked to imagine how unpleasant it would be to undergo that experience
      themselves, eliciting simulation. A localizer task identified regions-of-interest
      (ROIs) within each participant's sensorimotor cortices (SC) recruited by
      firsthand sensory experiences in hands and feet. Simulation engaged these ROIs in
      HC and SZ. Simulation-related activation in ROIs did not differ between groups
      but was associated with participants' social function. Findings indicate that
      simulation elicits specific neural representations within the SC and the strength
      of these representations might be linked to social function.

PMID- 29174438
TI  - Mendelian randomization analysis of cholesteryl ester transfer protein and
      subclinical atherosclerosis: A population-based study.
AB  - BACKGROUND: Several trials to prevent cardiovascular disease by inhibiting
      cholesteryl ester transfer protein (CETP) have failed, except Randomized
      EValuation of the Effects of Anacetrapib through Lipid-modification. Thus far, it
      is unclear to what extent CETP is causally related to measures of
      atherosclerosis. OBJECTIVE: The aim of the article was to study the causal
      relationship between genetically determined CETP concentration and carotid intima
      media thickness (cIMT) in a population-based cohort study. METHODS: In the
      Netherlands Epidemiology of Obesity study, participants were genotyped, and cIMT
      was measured by ultrasonography. We examined the relation between a weighted
      genetic risk score for CETP concentration, based on 3 single-nucleotide
      polymorphisms that have previously been shown to largely determine CETP
      concentration and cIMT using Mendelian randomization in the total population and
      in strata by sex, Framingham 10-year risk, (pre)diabetes, high-density
      lipoprotein cholesterol, triglycerides, and statin use. RESULTS: We analyzed 5655
      participants (56% women) with a mean age of 56 (range 44-66) years, body mass
      index of 26 (range 17-61) kg/m2, and serum CETP of 2.47 (range 0.68-5.33) MUg/mL.
      There was no evidence for a causal relation between genetically determined CETP
      and cIMT in the total population, but associations were differently directed in
      men (16 MUm per MUg/mL increase in genetically determined CETP; 95% confidence
      interval: -8, 39) and women (-8 MUm; -25, 9). Genetically determined CETP
      appeared to be associated with cIMT in normoglycemic men (26 MUm; -1, 52) and in
      (pre)diabetic women (48 MUm; -2, 98). CONCLUSION: In this population-based study,
      there was no causal relation between genetically determined CETP concentration
      and cIMT in the total population although we observed directionally differing
      effects in men and women. Stratified results suggested associations in
      individuals with different cardiometabolic risk factor profiles, which require
      replication.

PMID- 29174439
TI  - Vascular inflammation and metabolic activity in hematopoietic organs and liver in
      familial combined hyperlipidemia and heterozygous familial hypercholesterolemia.
AB  - BACKGROUND: Familial dyslipidemias of either heterozygous (heFH) or combined
      (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk.
      OBJECTIVE: The aim of this study was to investigate in statin-naive adult
      patients with familial dyslipidemias whether inflammatory activation and liver,
      spleen and bone marrow metabolic activity differ compared with normolipidemic
      subjects and between dyslipidemic groups. METHODS: Fourteen patients with FCH, 14
      with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high
      sensitivity C-reactive protein, and fibrinogen levels were measured, followed by
      18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging.
      Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was
      quantified as tissue-to-background ratio (TBR). RESULTS: Patients with heFH had
      significantly higher low-density lipoprotein levels compared with those with FCH
      and controls (P < .001). However, aortic TBRs were higher in FCH compared with
      heFH patients and controls (P = .02 and P < .001, respectively). FCH patients
      exhibited higher FDG uptake in the spleen compared with controls (P = .05). In
      addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients
      and controls (P = .03 and P = .02, respectively). FCH had higher liver uptake
      compared with heFH patients and controls (P < .001 for both). Significant
      correlations were observed between inflammatory biomarkers and imaging indices as
      well as between aortic TBR and FDG uptake of hematopoietic organs and liver.
      CONCLUSIONS: Systemic, as well as vascular inflammation and spleen, bone marrow,
      and hepatic metabolic activity are increased in patients with FCH despite lower
      levels of low-density lipoprotein.

PMID- 29174440
TI  - Immunochemotherapy mediated by thermosponge nanoparticles for synergistic anti
      tumor effects.
AB  - The efficacy of immunotherapy was demonstrated to be compromised by reduced
      immunogenicity of tumor cells and enhanced suppressive properties of the tumor
      microenvironment in cancer treatment. There is growing evidence that low-dose
      chemotherapy can modulate the immune system to improve the anti-tumor effects of
      immunotherapy through multiple mechanisms, including the enhancement of tumor
      immunogenicity and reversal of the immunosuppressive tumor microenvironment.
      Here, we fabricated thermosponge nanoparticles (TSNs) for the co-delivery of
      chemotherapeutic drug paclitaxel (PTX) and immunostimulant interleukin-2 (IL-2)
      to explore the synergistic anti-tumor effects of chemotherapy and immunotherapy.
      The distinct temperature-responsive swelling/deswelling character facilitated the
      effective post-entrapment of cytokine IL-2 in nanoparticles by a facile non
      solvent mild incubation method with unaffected bioactivity and favorable
      pharmacokinetics. PTX and IL-2 co-loaded TSNs exhibited significant inhibition on
      tumor growth and metastasis, and prolonged overall survival for tumor-bearing
      mice compared with the corresponding monotherapies. The synergistic effect was
      evidenced from the remodeled tumor microenvironment in which low-dose
      chemotherapeutics disrupted the immunosuppressive tumor microenvironment and
      enhanced tumor immunogenicity, and immunostimulant cytokine promoted the anti
      tumor immune response of immune effector cells. The immunochemotherapy mediated
      by this thermosponge nanoplatform may provide a promising treatment strategy
      against cancer.

PMID- 29174441
TI  - Hollow microneedle-mediated micro-injections of a liposomal HPV E743-63 synthetic
      long peptide vaccine for efficient induction of cytotoxic and T-helper responses.
AB  - Recent studies have shown that intradermal vaccination has great potential for T
      cell-mediated cancer immunotherapy. However, classical intradermal immunization
      with a hypodermic needle and syringe has several drawbacks. Therefore, in the
      present study a digitally controlled hollow microneedle injection system (DC-hMN
      iSystem) with an ultra-low dead volume was developed to perform micro-injections
      (0.25-10MUL) into skin in an automated manner. A synthetic long peptide derived
      from human papilloma virus formulated in cationic liposomes, which was used as a
      therapeutic cancer vaccine, was administered intradermally by using the DC-hMN
      iSystem. Fused silica hollow microneedles with an inner diameter of 50MUm and a
      bevel length of 66+/-26MUm were successfully fabricated via hydrofluoric acid
      etching. Upon piercing these microneedles into the skin using a protrusion length
      of 400MUm, microneedles were inserted at a depth of 350+/-55MUm. Micro-injections
      of 1-10MUL had an accuracy between 97 and 113% with a relative standard deviation
      (RSD) of 9%, and lower volumes (0.25 and 0.5MUL) had an accuracy of 86-103% with
      a RSD of 29% in ex vivo human skin. Intradermal administration of the therapeutic
      cancer vaccine via micro-injections induced strong functional cytotoxic and T
      helper responses in mice, while requiring much lower volumes as compared to
      classical intradermal immunization. In conclusion, by using the newly developed
      DC-hMN-iSystem, very low vaccine volumes can be precisely injected into skin in
      an automated manner. Thereby, this system shows potential for minimally-invasive
      and potentially pain-free therapeutic cancer vaccination.

PMID- 29174442
TI  - Health policy: A reflection and look forward.

PMID- 29174443
TI  - Persistent Dentoalveolar Pain Disorder: A Comprehensive Review.
AB  - INTRODUCTION: Persistent dentoalveolar pain of idiopathic origin represents a
      diagnostic challenge for the dentist and physician alike. Disagreement on
      taxonomy and diagnostic criteria presents a significant limit to the advancement
      of research in the field. Patients struggle with a lack of knowledge by dental
      and medical professionals, diagnostic delays, and unnecessary treatments.
      METHODS: A PubMed search was performed as of January 1, 2017 by using the terms
      atypical odontalgia, phantom tooth pain, persistent idiopathic facial pain,
      painful posttraumatic trigeminal neuropathy, idiopathic toothache, persistent
      dentoalveolar pain disorder, nonodontogenic tooth pain, and continuous
      neuropathic orofacial pain. Three hundred forty-five abstracts were screened, and
      128 articles that were pertinent to the topic went through full-text reading.
      RESULTS: Case reports and narrative reviews constitute the majority of available
      literature. Several retrospective case-control studies investigated the clinical
      characteristics, pathophysiology, and diagnostic processes. Treatment strategies
      were evaluated in only 7 open-label and 2 randomized controlled trials.
      CONCLUSIONS: Persistent dentoalveolar pain disorder is likely neuropathic in
      origin, but pathophysiological mechanisms to explain the onset and persistence of
      the pain are still far from understood. A correct diagnosis should be established
      before treatments are performed. Researchers should reach an agreement on the
      diagnostic criteria to enable a coherent research path to better understand the
      condition and reduce patient suffering.

PMID- 29174444
TI  - Clinical outcome of patients with suicide attempts: 1098 patients.

PMID- 29174445
TI  - Burn injury models of care: A review of quality and cultural safety for care of
      Indigenous children.
AB  - Safety and quality in the systematic management of burn care is important to
      ensure optimal outcomes. It is not clear if or how burn injury models of care
      uphold these qualities, or if they provide a space for culturally safe healthcare
      for Indigenous peoples, especially for children. This review is a critique of
      publically available models of care analysing their ability to facilitate safe,
      high-quality burn care for Indigenous children. Models of care were identified
      and mapped against cultural safety principles in healthcare, and against the
      National Health and Medical Research Council standard for clinical practice
      guidelines. An initial search and appraisal of tools was conducted to assess
      suitability of the tools in providing a mechanism to address quality and cultural
      safety. From the 53 documents found, 6 were eligible for review. Aspects of
      cultural safety were addressed in the models, but not explicitly, and were
      recorded very differently across all models. There was also limited or no
      cultural consultation documented in the models of care reviewed. Quality in the
      documents against National Health and Medical Research Council guidelines was
      evident; however, description or application of quality measures was inconsistent
      and incomplete. Gaps concerning safety and quality in the documented care
      pathways for Indigenous peoples' who sustain a burn injury and require burn care
      highlight the need for investigation and reform of current practices.

PMID- 29174446
TI  - Protective effect of ethyl acetate fraction of Drynaria quercifolia against CCl4
      induced rat liver fibrosis via Nrf2/ARE and NFkappaB signalling pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Drynaria quercifolia rhizome is traditionally
      used as hepatoprotective drug especially in chronic jaundice. AIM OF THE STUDY:
      The present study was undertaken to scientifically evaluate the efficacy of D.
      quercifolia rhizome against liver fibrosis. MATERIALS AND METHODS: D. quercifolia
      rhizome crude extract (DQ) and its fractions of hexane (HDQ), ethyl acetate
      (EDQ), butanol (BDQ) were evaluated in vitro using primary hepatocytes and RAW
      264.7 cells. In vivo anti-liver fibrotic activity of EDQ was assessed using CCl4
      induced liver fibrosis in Wistar rats and serum biochemical parameters (AST, ALT,
      ALP, SB, cholesterol), MDA, PT, INR, GSH, SOD, CAT, liver glycogen, serum albumin
      levels were monitored. qRT-PCR analysis of TNF-alpha, COX-2, iNOS were performed.
      ELISA method was used to estimate TNF-alpha, COX-1 & 2. Histopathological studies
      like H & E, Masson's trichrome, immunohistochemistry staining for alpha-SMA, TIMP
      1, Nrf2 were conducted. LC-Q-TOF-MS analysis of EDQ was conducted. RESULTS: In
      vitro activity guided fractionation of D. quercifolia revealed EDQ as active
      fraction when compared to other extracts. EDQ treatment significantly inhibited
      the expression of alpha-SMA, TIMP-1, COX-2, TNF-alpha, iNOS and increased the
      levels of Nrf2 in rat liver fibrosis. LC-Q-TOF-MS analysis of EDQ confirmed the
      presence of naringin and naringenin. CONCLUSION: The anti-liver fibrotic activity
      of EDQ is via inhibition of NFkappaB signalling pathway, antioxidant response
      through Nrf2 activation and further inhibition of HSC activation.

PMID- 29174447
TI  - Genetic diversity of Hepatozoon spp. in Hydrochoerus hydrochaeris and Pecari
      tajacu from eastern Amazon.
AB  - This study aimed to identify and characterize genetically species of the genus
      Hepatozoon detected in Hydrochoerus hydrochaeris (capybaras) and Pecari tajacu
      (collared peccaries) from two localities from the Eastern Amazon. Blood samples
      from 196 free-living H. hydrochaeris from Marajo Island and 109 P. tajacu kept in
      captivity in Belem, Para, were collected and analyzed for the presence of
      Hepatozoon spp. Partial sequences of the 18S rRNA gene were obtained and analyzed
      in comparison to others available in the NCBI database. Our results demonstrated
      a high prevalence of Hepatozoon canis in both mammals and the existence of four
      haplotypes of Hepatozoon spp., three of Hepatozoon canis and one of Hepatozoon
      cuestensis, found only in H. hydrochaeris. In addition, these data increase the
      genetic diversity of H. canis from the Eastern Amazon, as well as reporting, for
      the first time, the infection of mammals by H. cuestensis and P. tajacu by H.
      canis.

PMID- 29174448
TI  - Conspecific hyperparasitism: An alternative route for Borrelia hermsii
      transmission by the tick Ornithodoros hermsi.
AB  - Ixodid and argasid ticks may hyperparasitize other individuals of their own
      species to acquire a blood meal, however most accounts are based on single
      observations and the behavior has rarely been studied. While maintaining
      laboratory colonies of Ornithodoros species, we noticed that unfed ticks
      occasionally fed on other ticks that were feeding on mice, and unfed ticks
      parasitized engorged ticks when confined together in tubes. Therefore, we
      investigated hyperparasitism by Ornithodoros hermsi and the ability of these
      ticks to acquire and transmit the relapsing fever spirochete Borrelia hermsii
      when feeding on other ticks. Various combinations of unfed and recently engorged
      male, female and nymphal ticks were confined for 1-2h as individual pairs or in
      groups, then examined to determine the number of ticks that acquired blood by
      feeding on others. Unfed O. hermsi males were far more likely to hyperparasitize
      other ticks than were females and nymphs, as 78.6% of males (114 of 145 ticks)
      fed when confined with recently engorged ticks. Unfed females and nymphs also
      hyperparasitized other ticks but far less frequently (only 6.7% combined; 17 of
      254 ticks). Infection experiments demonstrated that unfed males acquired B.
      hermsii when parasitizing nymphs that had recently engorged on a spirochetemic
      mouse, and unfed infected males transmitted spirochetes to recently engorged
      nymphs. Some ticks infected via hyperparasitism subsequently transmitted B.
      hermsii to mice. Hyperparasitism by O. hermsi occurred more frequently than
      expected, although possibly influenced by our experimental design. The
      significance of this behavior as it may influence the horizontal transfer of B.
      hermsii in nature is not known but worthy of future consideration.

PMID- 29174449
TI  - Risk factors for tick exposure in suburban settings in the Northeastern United
      States.
AB  - Prevention of tick-borne diseases requires an understanding of when and where
      exposure to ticks is most likely. We used an epidemiologic approach to define
      these parameters for residents of a Lyme-endemic region. Two persons in each of
      500 Connecticut households were asked to complete a log each night for one week
      during June, 2013. Participants recorded their whereabouts in 15min increments
      (indoors, outdoors in their yard, outdoors on others' private property, or
      outdoors in public spaces) and noted each day whether they found a tick on
      themselves. Demographic and household information was also collected. Logs were
      completed for 934 participants in 471 households yielding 51,895 time-place
      observations. Median participant age was 49 years (range 2-91 years); 52% were
      female. Ninety-one participants (9.8%) reported finding a tick during the week,
      with slightly higher rates among females and minors. Household factors positively
      associated with finding a tick included having indoor/outdoor pets (odds ratio
      (OR)=1.7; 95% confidence interval (CI): 1.1-2.9), the presence of a bird feeder
      in the yard (OR=1.9; CI:1.2-3.2), and presence of an outdoor dining area (OR=2.2;
      CI:1.1-4.3). Individual factors associated with finding a tick on a given day
      were bathing or showering (OR=3.7; CI:1.3-10.3) and hours spent in one's own yard
      (OR=1.2, CI:1.1-1.3). Nineteen participants found ticks on multiple days, more
      than expected assuming independence (p<0.001). Participants who found ticks on
      multiple days did not spend more time outdoors but were significantly more likely
      to be male than those finding ticks on a single day (p<0.03). Our findings
      suggest that most tick exposures in the study area occurred on private property
      controlled by the respective homeowner. Interventions that target private yards
      are a logical focus for prevention efforts.

PMID- 29174450
TI  - We all make choices: A decision analysis framework for disposition decision in
      the ED.
AB  - BACKGROUND: Emergency Department (ED) providers' disposition decision impacts
      patient care and safety. The objective of this brief report is to gain a better
      understanding of ED providers' disposition decision and risk tolerance of
      associated outcomes. METHODS: We synthesized qualitative and quantitative methods
      including decision mapping, survey research, statistical analysis, and word
      clouds. Between July 2017 and August 2017, a 10-item survey was developed and
      conducted at the study hospital. Descriptive and statistical analyses were used
      to assess the relationship between the participant characteristics (age, gender,
      years of experience in the ED, and level of expertise) and risk tolerance of
      outcomes (72-h return and negative outcome) associated with disposition decision.
      Word clouds facilitated prioritization of qualitative responses regarding
      information impacting and supporting the disposition decision. RESULTS: Total of
      46 participants completed the survey. The mean age was 39.5 (standard deviation
      (SD) 10years), and mean years of experience was 9.6years (SD 8.7years). Decision
      map highlighted the connections between patient-, provider-, and system-related
      factors. Survey results showed that negative outcome resulted in less risk
      tolerance compared to 72-h return. Chi-square tests did not provide sufficient
      evidence to indicate that the responses are independent of participants
      characteristics - except age and the risk of 72-h return (p=0.046). CONCLUSION:
      Discharge decision making in the ED is complex as it involves interconnected
      patient, provider, and system factors. Synthesizing qualitative and quantitative
      methods promise enhanced understanding of how providers arrive to disposition
      decision, as well as safety and quality of care in the ED.

PMID- 29174451
TI  - Revolutionizing ECMO simulation with affordable yet high-Fidelity technology.

PMID- 29174452
TI  - Diagnosing centrally located pulmonary embolisms in the emergency department
      using point-of-care ultrasound.
AB  - OBJECTIVE: The study objective was to investigate the combined accuracy of right
      heart strain on focused cardiac ultrasound (FOCUS) and deep vein thrombosis (DVT)
      on compression ultrasound (CUS) for identification of centrally located pulmonary
      embolism (PE) diagnosed on computed tomography pulmonary angiography (CTPA).
      METHODS: This was a prospective observational study using a convenience sample of
      patients undergoing CTPA in the emergency department (ED) for evaluation of PE.
      Patients received a FOCUS looking for right heart strain (McConnell's sign,
      septal flattening, right ventricular enlargement or tricuspid annular plane
      systolic ejection (TAPSE) <17mm) and a CUS looking for DVT. Ultrasounds were
      interpreted by both the investigator performing the ultrasound and the principal
      investigator independently. RESULTS: There were 199 patients enrolled in the
      study, with 46/199 (23.1%) positive for a PE. Of these, 20/46 (43.5%) PE's were
      located centrally. Of those with a PE, 20/46 (43.5%) had an associated DVT
      identified on bedside ultrasound. Among patients with a proximal PE, 18/20
      (90.0%) had evidence of right heart strain and the combination of lower extremity
      CUS and FOCUS was 100% sensitive. Diagnostic accuracy of ultrasound was much
      lower for peripherally located PEs. CONCLUSIONS: Emergency physician-performed
      bedside ultrasound may be sufficient to exclude the presence of centrally located
      PE, as the sensitivity in this study was 100%. Additionally, several patients
      with PE may qualify for early anticoagulation when DVT is identified, and further
      research in indicated to determine whether these patients ultimately require CTPA
      given identical treatment algorithms in the absence of RV strain or biomarker
      elevation.

PMID- 29174453
TI  - Correlation of high flow nasal cannula outlet area with gas clearance and
      pressure in adult upper airway replicas.
AB  - BACKGROUND: Primary benefits of high flow nasal cannula therapy include washout
      of carbon dioxide rich exhaled gas and increased airway pressures during tidal
      breathing. This work reports on the influence of high flow nasal cannula outlet
      area on upper airways gas clearance and tracheal pressures using measurements in
      five realistic adult nose-throat airway replicas. METHODS: Two commercial high
      flow nasal cannulas and one generic nasal cannula of varying size were compared.
      100% oxygen was supplied via cannulas at flow rates ranging from 30 to 90l/min to
      replicas originally filled with air, and oxygen concentrations at the larynx and
      trachea were compared over time. Additionally, and separately, replicas were
      connected to a mechanical lung simulator to simulate tidal breathing while
      undergoing high flow nasal cannula therapy, with tracheal pressure-time waveforms
      recorded. FINDINGS: Faster gas clearance corresponded with higher flow rates
      (P<0.001), and with smaller cannula outlet area (P<0.001). Observed pressures
      were in approximate agreement with limited available in-vivo data in the
      literature. Between 0 and 60L/min cannula flow rates, tracheal positive end
      expiratory pressures increase was greater with the smallest cannula
      (?PPEEP=785SD(185) Pa) compared to the largest cannula (?PPEEP=380SD(120)Pa).
      Regression analysis indicates that positive end expiratory pressure is
      proportional to the square of flow velocities exiting the cannula and nares
      (R2=0.906). INTERPRETATION: Since increased pressure and clearance rate have been
      associated with improved clinical outcomes in previous studies, our results
      suggest that smaller cannula outlet area may be preferable.

PMID- 29174454
TI  - Closed incision negative pressure therapy decreases complications after
      periprosthetic fracture surgery around the hip and knee.
AB  - INTRODUCTION: Periprosthetic fractures (PPFXs) are becoming increasingly common
      following total hip arthroplasty (THA) and total knee arthroplasty (TKA).
      Patients sustaining PPFXs face considerable perioperative morbidity, with
      relatively increased rates of surgical site infection. We sought to evaluate the
      efficacy of closed-incision negative-pressure wound therapy (ciNPT) in decreasing
      perioperative wound complications following lower extremity periprosthetic
      fracture surgery. METHODS: We performed a retrospective review of 69 consecutive
      patients who underwent surgery to address lower extremity periprosthetic
      fractures around hip or knee implants performed over a 6.5-year period. The
      population was divided into two groups based on the surgical dressing used at the
      conclusion of the procedure: (1) a sterile, antimicrobial hydrofiber dressing, or
      (2) ciNPT. There were no baseline demographic differences between the two groups.
      Rates of wound complications, surgical site infection, and reoperation related to
      the surgical site were compared between groups. Continuous variables were
      analyzed using a student's t-test, and categorical variables using either chi
      square or fisher's exact test. RESULTS: Patients treated with ciNPT developed
      fewer wound complications (4% vs. 35%; p=0.002), fewer deep infections (0% vs.
      25%; p=0.004), and underwent fewer reoperations related to the surgical site (4%
      vs. 25%; p=0.021) compared to patients treated with standard of care.
      CONCLUSIONS: Our findings suggest that ciNPT may reduce wound complications,
      SSIs, and reoperations in patients undergoing lower extremity periprosthetic
      fracture surgery. This is the first study to investigate ciNPT as a treatment for
      periprosthetic fracture surgery, and has the potential to change the
      postoperative management of these patients.

PMID- 29174455
TI  - High power beta electron device - Beyond betavoltaics.
AB  - Developing watt level power sources with beta emitting radioisotopes has been
      limited by the inability to utilize high energy (> 100KeV) beta emitters at high
      radioisotope loadings without damaging the energy conversion materials. A new
      type of beta electron power source is described that removes those restrictions.
      The approach contains the radioisotope in a beta transparent titanium tube and
      confines beta electrons emitted through the tube wall to spiral trajectories
      around the tube with an axial magnetic field. The confined beta electrons
      dissipate energy though multiple interactions with surrounding excimer precursor
      gas atoms to efficiently generate photons. Photovoltaic cells convert the photons
      to electrical power. Since the beta electrons dissipate energy in the excimer
      precursor gas, the device can be loaded with more than 1013Bq of radioisotope to
      generate 100 milliwatt to watt levels of electrical power without damaging the
      device materials or degrading its performance. The power source can use a variety
      of beta radioisotopes and scales by stacking the devices.

PMID- 29174456
TI  - Prevalence of and risk factors for mental disorders in refugees.
AB  - Given the increasing numbers of refugees worldwide, the prevalence of their
      mental disorders is relevant for public health. Prevalence studies show that, in
      the first years of resettlement, only post-traumatic stress disorder (PTSD) rates
      are clearly higher in refugees than in host countries' populations. Five years
      after resettlement rates of depressive and anxiety disorders are also increased.
      Exposure to traumatic events before or during migration may explain high rates of
      PTSD. Evidence suggests that poor social integration and difficulties in
      accessing care contribute to higher rates of mental disorders in the long-term.
      Policy and research implications are discussed.

PMID- 29174457
TI  - What does the shape of our back tell us? Correlation between sacrum orientation
      and lumbar lordosis.
AB  - BACKGROUND CONTEXT: Sacral slope and lumbar lordosis (LL) have been studied
      extensively in recent years via X-ray examinations and strongly correlate with
      each other. This raises, first, the question of the reproducibility of this
      correlation in multiple standing phases and, second, if this correlation can be
      achieved using non-radiological measurement tools. PURPOSE: This study aimed (1)
      to determine the extent to which the back-shape measurements correspond to the
      correlations between the sacral slope and LL found in previous radiological
      investigations, (2) to identify a possible effect of age and gender on this
      correlation, and (3) to evaluate the extent to which this correlation is affected
      by repeated standing phases. STUDY DESIGN/SAMPLE: This is an observational cohort
      study. PATIENT SAMPLE: A total of 410 asymptomatic subjects (non-athletes), 21
      asymptomatic soccer players (athletes), and 176 patients with low back pain (LBP)
      were included. OUTCOME MEASURES: The correlation between sacrum orientation (SO)
      and LL was determined in six repetitive upright standing postures. MATERIALS AND
      METHODS: A non-invasive strain-gauge based measuring system was used. RESULTS:
      Back-shape measurements yielded a similar correlation to that measured in
      previous X-ray examinations. The coefficient of determination (R2) between SO and
      LL ranged between 0.76 and 0.79 for the asymptomatic cohort. Athletes showed the
      strongest correlation (0.76<=R2<=0.84). For patients with LBP, the correlation
      substantially decreased (0.18<=R2<=0.39). R2 was not strongly affected by
      repeated standing phases. CONCLUSIONS: The correlation between SO and LL can be
      assessed by surface measurements of the back shape and is not influenced by
      natural variations in the standing posture.

PMID- 29174458
TI  - Anterior cement augmentation of adjacent levels after vertebral body replacement
      leads to superior stability of the corpectomy cage under cyclic loading-a
      biomechanical investigation.
AB  - BACKGROUND: In the operative treatment of osteoporotic vertebral body fractures,
      a dorsal stabilization in combination with a corpectomy of the fractured
      vertebral body might be necessary with respect to the fracture morphology,
      whereby the osteoporotic bone quality may possibly increase the risk of implant
      failure. To achieve better stability, it is recommended to use cement-augmented
      screws for dorsal instrumentation. Besides careful end plate preparation, cement
      augmentation of the adjacent end plates has also been reported to lead to less
      reduction loss. PURPOSE: The aim of the study was to evaluate biomechanically
      under cyclic loading whether an additional cement augmentation of the adjacent
      end plates leads to improved stability of the inserted cage. STUDY
      DESIGN/SETTING: Methodical cadaver study. MATERIALS AND METHODS: Fourteen fresh
      frozen human thoracic spines with proven osteoporosis were used (T2-T7). After
      removal of the soft tissues, the spine was embedded in Technovit (Kulzer,
      Germany). Subsequently, a corpectomy of T5 was performed, leaving the dorsal
      ligamentary structures intact. After randomization with respect to bone quality,
      two groups were generated: Dorsal instrumentation (cemented pedicle screws,
      Medtronic, Minneapolis, MN, USA)+cage implantation (CAPRI Corpectomy Cage, K2M,
      Leesburg, VA, USA) without additional cementation of the adjacent endplates
      (Group A) and dorsal instrumentation+cage implantation with additional cement
      augmentation of the adjacent end plates (Group B). The subsequent axial and
      cyclic loading was performed at a frequency of 1 Hz, starting at 400 N and
      increasing the load within 200 N after every 500 cycles up to a maximum of 2,200
      N. Load failure was determined when the cages sintered macroscopically into the
      end plates (implant failure) or when the maximum load was reached. RESULTS: One
      specimen in Group B could not be clamped appropriately into the test bench for
      axial loading because of a pronounced scoliotic misalignment and had to be
      excluded. The mean strength for implant failure was 1,000 N+/-258.2 N in Group A
      (no cement augmentation of the adjacent end plates, n=7); on average, 1,622.1+/
      637.6 cycles were achieved. In Group B (cement augmentation of the adjacent end
      plates, n=6), the mean force at the end of loading was 1,766.7 N+/-320.4 N; an
      average of 3,572+/-920.6 cycles was achieved. Three specimens reached a load of
      2,000 N. The differences between the two groups were significant (p=.006 and
      p=.0047) regarding load failure and number of cycles. CONCLUSIONS: Additional
      cement augmentation of the adjacent end plates during implantation of a vertebral
      body replacement in osteoporotic bone resulted in a significant increased
      stability of the cage in the axial cyclic loading test.

PMID- 29174459
TI  - Prognosis of sciatica and back-related leg pain in primary care: the ATLAS
      cohort.
AB  - BACKGROUND CONTEXT: Evidence is lacking on the prognosis and prognostic factors
      of back-related leg pain and sciatica in patients seeing their primary care
      physicians. This evidence could guide timely appropriate treatment and referral
      decisions. PURPOSE: The present study aims to describe the prognosis and
      prognostic factors in primary care patients with low back-related leg pain and
      sciatica. STUDY DESIGN: This is a prospective cohort study. PATIENT SAMPLE: The
      present study included adults visiting their family doctor with back-related leg
      pain in the United Kingdom. OUTCOME MEASURES: Information about pain, function,
      psychological, and clinical variables, was collected. Good outcome was defined as
      30% or more reduction in disability (Roland-Morris Disability Questionnaire).
      METHODS: Participants completed the questionnaires, underwent clinical
      assessments, received a magnetic resonance imaging scan, and were followed-up 12
      months later. Mixed-effects logistic regression evaluated the prognostic value of
      six a priori defined variable sets (leg pain duration, pain intensity,
      neuropathic pain, psychological factors, clinical examination, and imaging
      variables). A combined model, including variables from all models, examined
      independent effects. The National Institute for Health Research funded the study.
      There are no conflicts of interest. RESULTS: A total of 609 patients were
      included. At 12 months, 55% of patients improved in both the total sample and the
      sciatica group. For the whole cohort, longer leg pain duration (odds ratio [OR]
      0.41; confidence interval [CI] 0.19-0.90), higher identity score (OR 0.70; CI
      0.53-0.93), and patient's belief that the problem will last a long time (OR 0.27;
      CI 0.13-0.57) were the strongest independent prognostic factors negatively
      associated with improvement. These last two factors were similarly negatively
      associated with improvement in the sciatica subgroup. CONCLUSIONS: The present
      study provides new evidence on the prognosis and prognostic factors of back
      related leg pain and sciatica in primary care. Just over half of patients
      improved at 12 months. Patient's belief of recovery timescale and number of other
      symptoms attributed to the pain are independent prognostic factors. These factors
      can be used to inform and direct decisions about timing and intensity of
      available therapeutic options.

PMID- 29174460
TI  - Long-term outcomes of transforaminal lumbar interbody fusion in patients with
      spinal stenosis and degenerative scoliosis.
AB  - BACKGROUND CONTEXT: Patients with spinal deformity may present with complaints
      related to either the deformity itself or the manifestations of the coexisting
      spinal stenosis. There are reports of successful management of lumbar pathology
      in the absence of global sagittal or coronal imbalance, with limited
      decompression and fusion, addressing only the symptomatic segment. PURPOSE: Our
      study examined the long-term outcomes of transforaminal lumbar interbody fusion
      (TLIF), a less extensive procedure, based on the experience of the senior author
      over the past 10 years. STUDY DESIGN/SETTING: This was a retrospective study of
      symptomatic lumbar spinal stenosis and spinal deformity managed by one surgeon at
      The Cleveland Clinic since 2003. PATIENT SAMPLE: Forty-one patients were included
      in the study. OUTCOME MEASURES: The present study measures the long-term clinical
      functional outcomes of these patients through EQ-5D (EuroQol five dimensions
      questionnaire), PHQ-9 (Patient Health Questionnaire), and PDQ (Pain Disability
      Questionnaire) forms, along with documented radiographic parameters and Charlson
      Comorbidity Index (CCI). METHODS: There were no funding or potential conflicts of
      interest associated biases in the present study. Patients with symptomatic lumbar
      spinal stenosis with neutral global alignment in the sagittal and coronal planes
      and symptomatic stenosis at the deformity level were treated by limited fusion
      and TLIF, and had a follow-up period of at least 5 years. Excluded were patients
      under 18 years of age, had more than three levels of fusion, and had an active
      spinal malignancy or recent spinal trauma. The grouping variables were curve
      magnitude, revision surgeries, and TLIF levels. Clinical outcomes were compared
      in all the grouping variables. Analysis of variance (ANOVA) and chi-square tests
      were utilized; p<.05 was considered statistically significant. RESULTS: The
      average age and follow-up period were 66+/-10 and 7.5 years, respectively. There
      was no statistical difference between patients with curves measuring between 10
      degrees  and 20 degrees  and greater than 20 degrees  for EQ-5D, PHQ-9, and PDQ.
      Patients had worse PDQ data with larger curves compared with smaller curves at
      both 5 years and final follow-up. Although there was no statistical significance
      between preoperative coronal curve magnitude and revision surgeries, patients
      with curves greater than 20 degrees  had higher rates of revision surgeries (75%;
      p=.343) in the global lumbar curve deformity group. Although there was no
      statistical significance for patients who underwent revision surgeries,those
      patients had low PHQ-9 values at the final follow-up (p=.09). The revision
      surgery rate was 48% in one-level TLIF and 18% in two-level TLIF. Moderate pain
      disability scores were noticed for one-level TLIF patients (mean=75) compared
      with two-level TLIF patients (mean=27) at the final follow-up, and approached
      statistical significance in this comparison (p=.06). CONCLUSION: Although this
      topic has a limited audience to spinal deformity surgeons, the prevalence of
      patients who present with adult spinal deformities has been increasing. Short
      segment fusion, in the setting of modest spinal deformity, is a reasonable and
      safe option. Further study on the concept of short segment fusions in the growing
      patient population is required as more comprehensive fusions do have noted
      complication rates, and a compromise must be reached between the extent of
      surgery that is enough to provide pain relief and disability and the degree of
      surgery that is too much to be tolerated in terms of complication rates.

PMID- 29174461
TI  - Multivariate optimization of solvent bar microextraction combined with HPLC-UV
      for determination of trace amounts of vincristine in biological fluids.
AB  - In the current work, an efficient method named solvent bar microextraction-high
      performance liquid chromatography-UV detection (HPLC-UV) was developed for
      preconcentration and determining the trace amount of vincristine (VCR) in
      biological samples such as plasma and urine. Briefly, VCR was extracted from an
      aqueous sample with pH 10.7 (donor phase) into 1-octanol as the supported liquid
      membrane (SLM) which is inserted into the pores of the hollow fiber and followed
      by back extraction into an aqueous receiving phase (pH=3.1). Studying the factors
      affecting the extraction performance in order to achieve a high extraction
      efficiency, requires the design of experiments (DOE) approach. In this regards,
      diverse factors' effects including the pH value of donor and acceptor phases,
      extraction time, extraction temperature, stirring rate and salt content of the
      donor phase were considered. The optimum experimental condition was as following:
      pH of the source phase, 10.7; pH of the receiving phase, 3.1; stirring rate,
      1000rpm; extraction temperature, 51 degrees C; extraction time, 60min and 11.3%
      w/v NaCl in the sample solution. Under the optimal; extraction condition, a
      favorable preconcentration factor equal to 98.5 was achieved. The linearity range
      was obtained in the domain of 0.05-5mgL-1. The limits of detection and
      quantification were 0.015 and 0.05mgL-1. Within-day and between-day RSDs of the
      proposed SBME method were 4.1% and 12.5%, respectively. Finally, the
      applicability of the implemented SBME method was evaluated by the extraction and
      quantification of VCR from biological samples such as urine and plasma and
      satisfactory results were obtained.

PMID- 29174462
TI  - Critical Care and Personalized or Precision Medicine: Who needs whom?
AB  - The current paradigm of modern healthcare is a reactive response to patient
      symptoms, subsequent diagnosis and corresponding treatment of the specific
      disease(s). This approach is predicated on methodologies first espoused by the
      Cnidean School of Medicine approximately 2500years ago. More recently escalating
      healthcare costs and relatively poor disease treatment outcomes have fermented a
      rethink in how we carry out medical practices. This has led to the emergence of
      "P-Medicine" in the form of Personalized and Precision Medicine. The terms are
      used interchangeably, but in fact there are significant differences in the way
      they are implemented. The former relies on an "N-of-1" model whereas the latter
      uses a "1-in-N" model. Personalized Medicine is still in a fledgling and
      evolutionary phase and there has been much debate over its current status and
      future prospects. A confounding factor has been the sudden development of
      Precision Medicine, which has currently captured the imagination of policymakers
      responsible for modern healthcare systems. There is some confusion over the terms
      Personalized versus Precision Medicine. Here we attempt to define the key
      differences and working definitions of each P-Medicine approach, as well as a
      taxonomic relationship tree. Finally, we discuss the impact of Personalized and
      Precision Medicine on the practice of Critical Care Medicine (CCM). Practitioners
      of CCM have been participating in Personalized Medicine unknowingly as it takes
      the protocols of sepsis, mechanical ventilation, and daily awakening trials and
      applies it to each individual patient. However, the immediate next step for CCM
      should be an active development of Precision Medicine. This developmental process
      should break down the silos of modern medicine and create a multidisciplinary
      approach between clinicians and basic/translational scientists.

PMID- 29174463
TI  - Critical care of tropical disease in low income countries: Report from the Task
      Force on Tropical Diseases by the World Federation of Societies of Intensive and
      Critical Care Medicine.
AB  - Tropical disease results in a great burden of critical illness. The same life
      saving and supportive therapies to maintain vital organ functions that comprise
      critical care are required by these patients as for all other diseases. In low
      income countries, the little available data points towards high mortality rates
      and big challenges in the provision of critical care. Improving critical care in
      low income countries requires a focus on hospital design, training, triage,
      monitoring & treatment modifications, the basic principles of critical care,
      hygiene and the involvement of multi-disciplinary teams. As a large proportion of
      critical illness from tropical disease is in low income countries, the impact and
      reductions in mortality rates of improved critical care in such settings could be
      substantial.

PMID- 29174464
TI  - Major contraindication to the endotoxemia activity assay in septic shock patients
      - Authors' reply.

PMID- 29174465
TI  - Reply to Joshua A. Linscott, Angela B. Smith, and Jesse D. Sammon's Letter to the
      Editor re: Woonyoung Choi, Andrea Ochoa, David J. McConkey, et al. Genetic
      Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the
      Cancer Genome Atlas Dataset. Eur Urol 2017;72:354-65.

PMID- 29174466
TI  - Re: Effect of Longer-interval Versus Standard Dosing of Zoledronic Acid on
      Skeletal Events in Patients with Bone Metastases.

PMID- 29174467
TI  - Medical Expulsive Therapy for Distal Ureteral Stones: The Verdict is In.

PMID- 29174468
TI  - Identification and characterization of the novel m.8305C>T MTTK and m.4440G>A
      MTTM gene mutations causing mitochondrial myopathies.
AB  - We report on two novel mtDNA mutations in patients affected with mitochondrial
      myopathy. The first patient, a 44-year-old woman, had bilateral eyelid ptosis and
      the m.8305C>T mutation in the MTTK gene. The second patient, a 56-year-old man,
      had four-limb muscle weakness and the MTTM gene m.4440G>A mutation. Muscle
      biopsies in both patients showed ragged red fibers and numerous COX-negative
      fibers as well as a combined defect of complex I, III and IV activities. The two
      mutations were heteroplasmic and detected only in muscle tissue, with a higher
      mutation load in COX-negative fibers. Additionally, both mutations occurred in
      highly conserved mt-tRNA sites, and were not found by an in silico search in
      30,589 human mtDNA sequences. Our report further expands the mutational and
      phenotypic spectrum of diseases associated with mutations in mitochondrial tRNA
      genes and reinforces the notion that mutations in mitochondrial tRNAs represent
      hot spots for mitochondrial myopathies in adults.

PMID- 29174469
TI  - Boundary cap cells in development and disease.
AB  - Broad plasticity of the peripheral glia is an emerging concept during development
      of the peripheral nervous system (PNS). Recent studies have identified the neural
      crest-derived boundary caps (BCs), as a multitask stem cell population of the
      developing PNS. BC progeny migrate along the nerves to provide the major glial
      component of nerve roots and nerve terminals in the skin. Strikingly, those two
      locations constitute the privileged sites for development of benign peripheral
      nerve sheath tumors called neurofibromas in patients with neurofibromatosis type
      1 (NF1), making BCs attractive candidates for the 'cell of origin' of this
      disease. Here, we review these exciting findings, focusing on the origin and
      novel functions of BCs. We further discuss the heterogeneity of BCs, and address
      their implication in the pathogenesis of NF1.

PMID- 29174470
TI  - Associations Between Prostate Volume and Oncologic Outcomes in Men Undergoing
      Focal Cryoablation of the Prostate.
AB  - INTRODUCTION: The purpose of this study was to assess the relationship of total
      prostate volume (TPV) and oncologic outcomes following focal prostate
      cryoablation. MATERIALS AND METHODS: A query of the Cryo On-Line Database (COLD)
      registry for men who underwent primary focal prostate cryoablation revealed 829
      patients with complete data. The impact of TPV on oncologic outcomes including
      progression-free survival (PFS) and post-cryoablation biopsy outcome was assessed
      using Kaplan-Meier curves and Cox and logistic regression models. RESULTS: The
      median follow-up time was 25.2 months (interquartile range [IQR], 12.7-48.2
      months). The median age at time of treatment was 68 years (IQR, 63-74 years) with
      median prostate-specific antigen (PSA) 5.6 ng/mL (IQR, 4.4-7.5 ng/mL), and median
      TPV 35 mL (IQR, 26.5-46 mL). PFS was achieved in 83.2%, with positive post
      cryoablation biopsy detected in 81 (35.7%) of 228 patients. Higher TPV was
      associated with higher biochemical progression (BP) using the Phoenix definition
      (39 vs. 34.5 mL; P = .003) and was an independent predictor of BP (hazard ratio,
      1.01; P = .02). Conversely, men who had a positive post-cryoablation biopsy had
      significantly smaller median TPV on univariate and multivariate analyses (31 vs.
      39 mL; P < .001), (odds ratio, 0.97; P = .001), respectively. Higher median
      pretreatment PSA density was associated with higher BP (0.18 vs. 0.16; P = .005)
      and positive post-cryoablation biopsy rates (0.2 vs. 0.16; P = .003). CONCLUSION:
      Prostate volume has contradictory effects on BP and post-cryoablation biopsy
      outcome in men who underwent primary focal prostate cryoablation. Remnant viable
      tissue in larger prostates continues to produce more PSA over time, which may
      impact BP. This may raise the need to develop a new definition for oncologic
      success following focal gland therapy rather than the American Society for
      Radiation Oncology (ASTRO) and Phoenix definitions.

PMID- 29174471
TI  - Oncologic Outcomes of Partial Nephrectomy for Stage T3a Renal Cell Cancer.
AB  - BACKGROUND: Partial nephrectomy (PN) for clinical stage T3 tumors is
      controversial. Radical nephrectomy (RN) has been associated with a greater rate
      of chronic kidney disease, an increased risk of cardiovascular disease, and
      increased mortality compared with PN. We present our long-term 2-center
      experience with PN for stage pT3a tumors and compare the oncologic outcomes with
      those of similar patients treated with RN. MATERIALS AND METHODS: We reviewed the
      data from all patients who had undergone nephrectomy for renal cell carcinoma
      from 1987 to 2015 in 2 medical centers. The study included 134 patients with
      pathologic stage T3a tumors, of whom 48 and 86 underwent PN and RN, respectively.
      We compared the 2 groups (PN and RN) using univariate and multivariate analyses.
      RESULTS: The tumors of all patients with pathologic stage T3a who had undergone
      PN had been pathologically upstaged from clinical stage T1 or T2. Univariate and
      multivariate analyses revealed tumor size was significantly different
      statistically between the study groups (median, 7.0 cm in RN group vs. 4.0 cm in
      PN group; P < .001). Surgery type was not a predictor of local recurrence (P =
      .978), metastatic progression (P = .972), death from renal cancer (P = .626), or
      death from all causes (P = .974) at the 5-year follow-up point. CONCLUSION: The
      results of the present study have shown similar oncologic outcomes between 48
      patients with stage pT3a renal cancer who underwent PN and 86 patients who
      underwent RN. Although PN was not performed on clinical T3a tumors, our findings
      suggest that PN can also be considered for these tumors and, thus, avoid the long
      term complications of RN. However, strict follow-up protocols are mandatory.

PMID- 29174472
TI  - The influence of biodegradable magnesium implants on the growth plate.
AB  - : Mg-based biodegradable materials are considered promising candidates in the
      paediatric field due to their favourable mechanical and biological properties and
      their biodegrading potential that makes a second surgery for implant removal
      unnecessary. In many cases the surgical fixation technique requires a crossing of
      the growth plate by the implant in order to achieve an adequate fragment
      replacement or fracture stabilisation. This study investigates the kinetics of
      slowly and rapidly degrading Mg alloys in a transphyseal rat model, and also
      reports on their dynamics in the context of the physis and consecutive bone
      growth. Twenty-six male Sprague-Dawley rats received either a rapidly degrading
      (ZX50; n = 13) or a slowly degrading (WZ21; n = 13) Mg alloy, implanted
      transphyseal into the distal femur. The contralateral leg was drilled in the same
      manner and served as a direct sham specimen. Degradation behaviour, gas
      formation, and leg length were measured by continuous in vivo micro CT for up to
      52 weeks, and additional high-resolution uCT (HRS) scans and histomorphological
      analyses of the growth plate were performed. The growth plate was locally
      destroyed and bone growth was significantly diminished by the fast degradation of
      ZX50 implants and the accompanying release of large amounts of hydrogen gas. In
      contrast, WZ21 implants showed homogenous and moderate degradation performance,
      and the effect on bone growth did not differ significantly from a single drill
      hole defect. STATEMENT OF SIGNIFICANCE: This study is the first that reports on
      the effects of degrading magnesium implants on the growth plate in a living
      animal model. The results show that high evolution of hydrogen gas due to rapid
      Mg degradation can damage the growth plate substantially. Slow degradation,
      however, such as seen for WZ21 alloys, does not affect the growth plate more than
      drilling alone, thus meeting one important prerequisite for deployment in
      paediatric osteosynthesis.

PMID- 29174473
TI  - Distribution of cervical metastasis in tongue cancer: Are occult metastases
      predictable? A retrospective study of 117 oral tongue carcinomas.
AB  - PURPOSE: The aims of this study were to evaluate the pattern of distribution of
      cervical metastasis in tongue cancer and to analyze the various therapeutic
      options available. Moreover, numerous histological features were analyzed to
      assess the impact of each factor on overall survival. MATERIALS AND METHODS: A
      retrospective analysis was conducted using the records of patients diagnosed with
      oral tongue cancer between 2004 and 2010 in the Virgen de las Nieves University
      Hospital (HUVN). A total of 117 patients with squamous cell carcinoma of the
      tongue treated with glossectomy and selective neck dissection were included in
      the study. The pattern of distribution of cervical metastases and numerous
      histological features such as T-stage, N stage, surgical margins, tumor
      thickness, extracapsular spread (ECS) and vascular invasion were analyzed.
      RESULTS: Level IIA was the most affected, followed by level III. The rate of skip
      metastasis was 7,4%. T and N stage, tumor thickness, ECS, surgical margins and
      nerve and vascular invasion were associated with poorer outcomes in terms of
      overall survival (p < 0,001). CONCLUSION: Cervical nodal involvement represents
      the major prognostic factor in tongue cancer. A total of 51,2% of N+ patients
      presented T1 and T2 tumors in this series. We recommend performing neck
      dissection at the early stages in clinically N0 patients when a tumor thickness
      >0,4 cm is suspected. Level IV should be included in the neck dissection of
      clinically N0 tongue cancer.

PMID- 29174474
TI  - Iron overload in hematological disorders.
AB  - While most common symptom of impairment of iron homeostasis is iron deficiency
      anemia, some hematological disorders are associated with iron overload (IO).
      These disorders are related mainly to chronic severe hemolytic anemia, where red
      blood cells (RBC) or their precursors are destroyed prematurely (hemolyzed),
      leading to anemia that cannot be compensated by increased production of new RBC.
      In such cases, IO is mainly due to repeated RBC transfusions and/or increased
      uptake of iron in the gastrointestinal tract. Normally, iron is present in the
      plasma and in the cells bound to compounds that render it redox inactive. Iron
      overload leaves a fraction of the iron free (labile iron pool) and redox active,
      leading to the generation of excess free radicals such as the reactive oxygen
      species. This condition upsets the cellular redox balance between oxidants and
      antioxidants, leading to oxidative stress. The free radicals bind to various
      cellular components, thereby becoming toxic to vital organs. Oxidative stress may
      also affect blood cells, such as RBC, platelets and neutrophils, exacerbating the
      anemia, and causing recurrent infections and thrombotic events, respectively. The
      toxic effect of IO can be decreased by treating the patients with iron chelators
      that enter cells, bind free iron and remove it from the body through the urine
      and feces. Iron toxicity may be also ameliorated by treatment with anti-oxidants
      that scavenge free radicals and/or correct their damage. The use of iron
      chelators is widely accepted when started in young patients with severe chronic
      anemia, but is still debatable as a therapeutic modality for older patients
      suffering from IO due to myelodysplastic syndromes. It should be noted that in
      addition to preventing iron toxicity, some compounds with iron chelator activity
      may also benefit other aspects of hematological disorders. These aspects include
      stimulation of platelet production, inhibition of leukemic cell proliferation and
      induction of their differentiation. Compounds with such multiple activities may
      prove beneficial for at least some patients with leukemia and myelodysplastic
      syndromes.

PMID- 29174475
TI  - Temporal trends in the premorbid use of preventive treatments in patients with
      acute ischemic cerebrovascular events and a history of vascular disease: The
      Dijon Stroke Registry (1985-2010).
AB  - INTRODUCTION: Although secondary prevention in patients with arterial vascular
      diseases has improved, a gap between recommendations and clinical practice may
      exist. OBJECTIVES: We aimed to evaluate temporal trends in the premorbid use of
      preventive treatments in patients with ischemic cerebrovascular events (ICVE) and
      prior vascular disease. METHODS: Patients with acute ICVE (ischemic stroke/TIA)
      were identified through the population-based stroke registry of Dijon, France
      (1985-2010). Only those with history of arterial vascular disease were included
      and were classified into four groups: patients with previous coronary artery
      disease only (CAD), previous peripheral artery disease only (PAD), previous ICVE
      only, and patients with at least two different past vascular diseases
      (polyvascular group). We assessed trends in the proportion of patients who were
      treated with antihypertensive treatments and antithrombotics at the time of their
      ICVE using multivariable logistic regression models. RESULTS: Among the 5309
      patients with acute ICVE, 2128 had a history of vascular disease (mean age 77.3+/
      11.9, 51% men; 25.1% CAD 7.5% PAD, 39.8% ICVE, and 27.5% poylvascular). A total
      of 45.8% of them were on antithrombotics, 64.1% on antihypertensive treatment,
      and 34.4% on both. Compared with period 1985-1993, periods 1994-2002 and 2003
      2010 were associated with a greater frequency of prior-to-ICVE use of
      antithrombotics (adjusted OR=5.94; 95% CI: 4.61-7.65, P<0.01, and adjusted
      OR=6.92; 95% CI: 5.33-8.98, P<0.01, respectively) but not of antihypertensive
      drugs. Consistent results were found when analyses were stratified according to
      the type of history of arterial vascular disease. CONCLUSION: Patients with ICVE
      and previous vascular disease were still undertreated with recommended preventive
      therapies.

PMID- 29174476
TI  - Brown-Sequard syndrome caused by hyperextension in a patient with atlantoaxial
      subluxation due to an os odontoideum.
AB  - Brown-Sequard syndrome is an uncommon complication of atlantoaxial arthrodesis. A
      50-year-old female visited our emergency department after falling from a ladder.
      Radiologic evaluations revealed chronic C1-2 instability with acute spinal cord
      injury. The day after atlantoaxial fusion was performed, she developed left-sided
      motor weakness and the loss of right-sided pain and temperature sensation. Based
      on physical examination and radiologic findings, we diagnosed her as having Brown
      Sequard syndrome. Spine surgeons performing this procedure should therefore
      consider Brown-Sequard syndrome if a patient displays signs of postoperative
      hemiplegia.

PMID- 29174477
TI  - The effect of hip reconstruction on gross motor function levels in children with
      cerebral palsy.
AB  - OBJECTIVE: The aim of this study was to determine whether the hip reconstruction
      has an effect on gross motor function classification system (GMFCS) levels in
      patients with hip instability in cerebral palsy (CP). METHODS: A total of 45 hips
      of 30 patients (mean age: 8.7 (4-17) years) with CP operated due to hip
      instability with a minimum of 2 years of follow-up were included into the study.
      Migration index was used for classification of the severity of hip instability.
      Clinical evaluation included sitting and walking ability, existence of pressure
      sores, difficulty in perineal care, and hip pain. The functional gains from the
      surgery were evaluated with changes in GMFCS levels. Wilcoxon T test, chi-square
      test and Spearman correlation test were used. RESULTS: Mean follow-up time was 57
      (24-132) months. The distribution of preoperative GMFCS was level I in 1 patient,
      level II in 4 patients, level III in 5 patients, level IV in 9 patients and level
      V in 11 patients. The complaints resolved in 25 patients, and persisted in 5
      postoperatively. There was no correlation between the changes in GMFCS levels and
      the postoperative complaints (p = 0.504). The GMFCS levels did not change in 20
      patients, improved in 8, and worsened in 2. There were no significant differences
      between the preoperative and postoperative GMFCS levels (p = 0.052). Positive
      correlations were found between the preoperative GMFCS-MI, the type of CP-MI
      respectively (p = 0.001, p = 0.015). CONCLUSION: There was an improvement in
      preoperative complaints. GMFCS levels remained stable after surgery. Relief in
      symptoms was not consistent with the changes in GMFCS in children with cerebral
      palsy after hip reconstruction. LEVEL OF EVIDENCE: Level IV, Therapeutic study.

PMID- 29174478
TI  - Amygdala Inhibitory Circuits Regulate Associative Fear Conditioning.
AB  - Associative memory formation is essential for an animal's survival by ensuring
      adaptive behavioral responses in an ever-changing environment. This is
      particularly important under conditions of immediate threats such as in fear
      learning. One of the key brain regions involved in associative fear learning is
      the amygdala. The basolateral amygdala is the main entry site for sensory
      information to the amygdala complex, and local plasticity in excitatory
      basolateral amygdala principal neurons is considered to be crucial for learning
      of conditioned fear responses. However, activity and plasticity of excitatory
      circuits are tightly controlled by local inhibitory interneurons in a spatially
      and temporally defined manner. In this review, we provide an updated view on how
      distinct interneuron subtypes in the basolateral amygdala contribute to the
      acquisition and extinction of conditioned fear memories.

PMID- 29174480
TI  - Intravenous insulin therapy as a therapeutic option for severe
      hypertriglyceridaemia in a non-diabetes patient.

PMID- 29174479
TI  - Practical implementation, education and interpretation guidelines for continuous
      glucose monitoring: A French position statement.
AB  - The use by diabetes patients of real-time continuous interstitial glucose
      monitoring (CGM) or the FreeStyle Libre(r) (FSL) flash glucose monitoring (FGM)
      system is becoming widespread and has changed diabetic practice. The working
      group bringing together a number of French experts has proposed the present
      practical consensus. Training of professionals and patient education are crucial
      for the success of CGM. Also, institutional recommendations must pay particular
      attention to the indications for and reimbursement of CGM devices in populations
      at risk of hypoglycaemia. The rules of good practice for CGM are the precursors
      of those that need to be enacted, given the oncoming emergence of artificial
      pancreas devices. It is necessary to have software combining user-friendliness,
      multiplatform usage and average glucose profile (AGP) presentation, while
      integrating glucose and insulin data as well as events. Expression of CGM data
      must strive for standardization that facilitates patient phenotyping and their
      follow-up, while integrating indicators of variability. The introduction of CGM
      involves a transformation of treatment support, rendering it longer and more
      complex as it also includes specific educational and technical dimensions. This
      complexity must be taken into account in discussions of organization of diabetes
      care.

PMID- 29174481
TI  - A Comparison of Regorafenib and TAS-102 for Metastatic Colorectal Cancer: A
      Systematic Review and Network Meta-analysis.
AB  - BACKGROUND: Regorafenib and TAS-102 have shown to be superior to placebo in
      refractory metastatic colorectal cancer. However, no studies have directly
      compared both drugs. Giving the lack of standard options in this scenario, a
      systematic review to compare the efficacy and safety of regorafenib and TAS-102
      was performed. MATERIALS AND METHODS: A systematic review using the PubMed,
      Medline, Embase, Scopus, and Cochrane databases to identify published and
      unpublished studies up to November 2015 for randomized controlled trials for
      patients with metastatic colorectal cancer, involving regorafenib or TAS-102, was
      performed. Data including overall survival, progression-free survival, and
      toxicity were extracted. Pairwise direct meta-analyses (regorafenib vs. placebo
      and TAS-102 vs. placebo) and indirect comparison (regorafenib vs. TAS-102) using
      network meta-analyses methods to preserve randomization were performed using
      random effects. RESULTS: Three randomized controlled trials fulfilled eligibility
      criteria (regorafenib monotherapy for previously treated metastatic colorectal
      cancer [CORRECT]: an international, multicentre, randomised, pacebo-controlled,
      phase 3 trial, regorafenib plus best supportive care versus placebo plus best
      supportive care in Asian patients with previously treated metastatic colorectal
      cancer [CONCUR]: a randomised, double-blind, placebo-controlled, phase 3 trial,
      and randomized trial of TAS-102 for refractory metastatic colorectal cancer
      [RECOURSE] trials) involving 1764 patients (regorafenib, 641; TAS-102, 534;
      placebo, 589). Subgroups of patients (1659) who had not received prior
      regorafenib or TAS-102 were used to perform meta-analyses for efficacy. In the
      indirect comparison, no statistically significant differences were observed
      between regorafenib and TAS-102 in overall survival (hazard ratio, 0.96; 95%
      confidence interval [CI], 0.57-1.66; P = .91) or progression-free survival
      (hazard ratio, 0.85; 95% CI, 0.40-1.81; P = .67). However, regorafenib has
      statistically more all grade any toxicity (risk difference, 0.31; 95% CI, 0.25
      0.38; P = .001) compared with TAS-102. Subgroup analysis of adverse events showed
      a different toxicity profile between both drugs. CONCLUSION: In this indirect
      comparison, regorafenib and TAS-102 appeared to have similar efficacy. However,
      regorafenib was associated with more toxicity compared with TAS-102.

PMID- 29174482
TI  - Re: Follow-up of Prostatectomy Versus Observation for Early Prostate Cancer.

PMID- 29174483
TI  - How glucocorticoids change life in Duchenne muscular dystrophy.

PMID- 29174485
TI  - Navigation of Fluorescence Cameras during Soft Tissue Surgery-Is it Possible to
      Use a Single Navigation Setup for Various Open and Laparoscopic Urological
      Surgery Applications?
AB  - PURPOSE: Real-time visualization fluorescence imaging can guide surgeons during
      tissue resection. Unfortunately tissue induced signal attenuation limits the
      value of this technique to superficial applications. By positioning the
      fluorescence camera via a dedicated navigation setup we reasoned that the
      technology could be made compatible with deeper lesions, increasing its impact on
      clinical care. Such an impact would benefit from the ability to implement the
      navigation technology in different surgical settings. For that reason we
      evaluated whether a single fluorescence camera could be navigated toward targeted
      lesions during open and laparoscopic surgery. MATERIALS AND METHODS: A
      fluorescence camera with scopes available for open and laparoscopic procedures
      was integrated with a navigation platform. Lymph nodes identified on SPECT/CT
      (single photon emission computerized tomography/computerized tomography) or free
      hand single photon emission computerized tomography acted as navigation targets
      and were displayed as augmented overlays in the fluorescence camera video feed.
      The accuracy of this setup was evaluated in a phantom study of 4 scans per single
      photon emission computerized tomography imaging modality. This was followed by 4
      first in human translations into sentinel lymph node biopsy procedures for penile
      (open surgery) and prostate (laparoscopic surgery) cancer. RESULTS: Overall the
      phantom studies revealed a tool-target distance accuracy of 2.1 mm for SPECT/CT
      and 3.2 mm for freehand single photon emission computerized tomography, and an
      augmented reality registration accuracy of 1.1 and 2.2 mm, respectively.
      Subsequently open and laparoscopic navigation efforts were accurate enough to
      localize the fluorescence signals of the targeted tissues in vivo. CONCLUSIONS:
      The phantom and human studies performed suggested that the single navigation
      setup is applicable in various open and laparoscopic urological surgery
      applications. Further evaluation in larger patient groups with a greater variety
      of malignancies is recommended to strengthen these results.

PMID- 29174484
TI  - Long-term effects of glucocorticoids on function, quality of life, and survival
      in patients with Duchenne muscular dystrophy: a prospective cohort study.
AB  - BACKGROUND: Glucocorticoid treatment is recommended as a standard of care in
      Duchenne muscular dystrophy; however, few studies have assessed the long-term
      benefits of this treatment. We examined the long-term effects of glucocorticoids
      on milestone-related disease progression across the lifespan and survival in
      patients with Duchenne muscular dystrophy. METHODS: For this prospective cohort
      study, we enrolled male patients aged 2-28 years with Duchenne muscular dystrophy
      at 20 centres in nine countries. Patients were followed up for 10 years. We
      compared no glucocorticoid treatment or cumulative treatment duration of less
      than 1 month versus treatment of 1 year or longer with regard to progression of
      nine disease-related and clinically meaningful mobility and upper limb
      milestones. We used Kaplan-Meier analyses to compare glucocorticoid treatment
      groups for time to stand from supine of 5 s or longer and 10 s or longer, and
      loss of stand from supine, four-stair climb, ambulation, full overhead reach,
      hand-to-mouth function, and hand function. Risk of death was also assessed. This
      study is registered with ClinicalTrials.gov, number NCT00468832. FINDINGS: 440
      patients were enrolled during two recruitment periods (2006-09 and 2012-16). Time
      to all disease progression milestone events was significantly longer in patients
      treated with glucocorticoids for 1 year or longer than in patients treated for
      less than 1 month or never treated (log-rank p<0.0001). Glucocorticoid treatment
      for 1 year or longer was associated with increased median age at loss of mobility
      milestones by 2.1-4.4 years and upper limb milestones by 2.8-8.0 years compared
      with treatment for less than 1 month. Deflazacort was associated with increased
      median age at loss of three milestones by 2.1-2.7 years in comparison with
      prednisone or prednisolone (log-rank p<0.012). 45 patients died during the 10
      year follow-up. 39 (87%) of these deaths were attributable to Duchenne-related
      causes in patients with known duration of glucocorticoids usage. 28 (9%) deaths
      occurred in 311 patients treated with glucocorticoids for 1 year or longer
      compared with 11 (19%) deaths in 58 patients with no history of glucocorticoid
      use (odds ratio 0.47, 95% CI 0.22-1.00; p=0.0501). INTERPRETATION: In patients
      with Duchenne muscular dystrophy, glucocorticoid treatment is associated with
      reduced risk of losing clinically meaningful mobility and upper limb disease
      progression milestones across the lifespan as well as reduced risk of death.
      FUNDING: US Department of Education/National Institute on Disability and
      Rehabilitation Research; US Department of Defense; National Institutes of
      Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases; and
      Parent Project Muscular Dystrophy.

PMID- 29174486
TI  - Accumulation of steroid hormones in the eggshells of Japanese quail (Coturnix
      coturnix japonica).
AB  - Oviparous mother transfer significant amounts of steroid to egg yolk during
      oviposition and the amounts may vary throughout the embryonic development.
      Eggshell may contain steroid hormones and the amounts could be different during
      embryonic development inside the egg. This study was designed to quantify the
      steroid concentrations in the eggshells of Japanese quail. We hypothesized that
      the steroids would be accumulated in the eggshells in a sex-dependent manner.
      Eggshells were obtained from three different stages (after laying, 15 days of
      incubation, and after hatching). The internal contents of the shells were
      carefully removed, completely dried and pulverized. The steroid contents of the
      eggshells were then measured by RIA. Physiologic variations in steroids were
      analyzed according to the amounts accumulated in the eggshells with the different
      embryonic stages. Results indicate that eggshell testosterone concentrations were
      high after laying. However, the concentrations were decreased during embryonic
      development and hatching and no difference was found in eggshell testosterone
      levels between male and female. However, eggshell estradiol concentrations were
      undetectable at laying time and the amounts were significantly increased at 15
      days of incubation and slightly after hatching. Eggshell estradiol levels were
      significantly high in female eggshells than male during embryonic development. In
      contrast, eggshell corticosterone levels were significantly higher in males than
      in females after hatching. These results clearly demonstrated that eggshells
      accumulated steroid hormones, and the amounts varied during embryonic development
      concomitant with changes the internal contents of the eggs.

PMID- 29174487
TI  - miRNAome, mRNAome and degradome analysis of Tibetan minipigs anterior pituitary.
AB  - Tibetan minipig is an important animal model for human diseases. The anterior
      pituitary is the master gland responsible for growth, reproduction, and
      metabolism and is regulated by thousands of miRNAs/mRNAs molecules. However,
      little is known about miRNAs and their relationships with mRNAs in Tibetan
      minipig anterior pituitary. Using microarray and mRNA-Sequencing, we identified
      203 miRNAs and 12,040 mRNA transcripts from the anterior pituitary of Tibetan
      minipigs. These miRNAs were corresponding to 194 hairpin precursors, 25 miRNA
      clusters and 24 miRNA families. In addition, 64 intragenic miRNAs were annotated.
      Using three bioinformatic algorithms (TargetScan, miRanda and RNAhybrid), 359,184
      possible miRNA-mRNA interactions were predicted, and an integrated network of
      miRNAs and pituitary-specific mRNA transcripts was established. To validate the
      predicted results, the degradome sequencing was employed to confirm miRNA-mRNA
      interactions, totally, 30 miRNA-mRNA pairs were identified. The present study
      provided a general overview of miRNA and mRNA annotation in Tibetan minipig
      anterior pituitary and established a miRNA-mRNA interactions database at the
      whole genome scale, which helps shed light on the molecular mechanisms in the
      anterior pituitary of pigs even other mammals.

PMID- 29174488
TI  - Endpoints in sarcoidosis: More like IPF or asthma?

PMID- 29174489
TI  - Social transmission and shared reality in cultural dynamics.
AB  - Micro cultural dynamics are concerned with the mechanisms of transmission,
      retention, and modification of cultural information in social networks. When
      interacting individuals mutually recognize that they share psychological
      reactions to given cultural information, it may be grounded as an aspect of their
      shared reality under specifiable conditions. The interpretation of cultural
      information as socially verified shared reality provides a basis for further
      dissemination of the information and coordinated social action. We review the
      recent literature that supports this general contention, while highlighting the
      role of emotion-a somewhat under-recognized aspect of shared reality research-and
      emphasizing the mediating role of cultural dynamics in the mutual constitution of
      social reality and shared reality.

PMID- 29174490
TI  - Risk of Cardiac Events Associated With Antidepressant Therapy in Patients With
      Long QT Syndrome.
AB  - Patients with long QT syndrome (LQTS) are at a high risk of cardiac events. Many
      patients with LQTS are treated with antidepressant drugs (ADs). We investigated
      the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs)
      associated with AD therapy. The study included 59 LQT1 and 72 LQT2 patients from
      the Rochester-based LQTS Registry with corrected QT (QTc) prolongation and a
      history of AD therapy. Using multivariate Anderson-Gill models, we estimated the
      LQTS genotype-specific risk of recurrent CAEs (ventricular tachyarrhythmias,
      aborted cardiac arrest, or sudden cardiac death) associated with time-dependent
      ADs. Specifically, we examined the risk associated with all ADs, selective
      serotonin reuptake inhibitor (SSRI), and ADs classified on the CredibleMeds list
      (www.CredibleMeds.org) as "Conditional" or "Known risk of Torsades de pointes
      (TdP)." After adjusting for baseline QTc duration, sex, and time-dependent beta
      blocker usage, there was an increased risk of recurrent CAEs associated with ADs
      in LQT1 patients (hazard ratio = 3.67, 95% confidence interval 1.98-6.82, p <
      0.001) but not in LQT2 patients (hazard ratio = 0.89, 95% confidence interval
      0.49-1.64, p = 0.716; LQT1 vs LQT2 interaction, p < 0.001). Similarly, LQT1
      patients who were on SSRIs or ADs with "Known risk of TdP" had a higher risk of
      recurrent CAEs than those patients off all ADs, whereas there was no association
      in LQT2 patients. ADs with "Conditional risk of TdP" were not associated with the
      risk of recurrent CAEs in any of the groups. In conclusion, the risk of recurrent
      CAEs associated with time-dependent ADs is higher in LQT1 patients but not in
      LQT2 patients. Results suggest a LQTS genotype-specific effect of ADs on the risk
      of arrhythmic events.

PMID- 29174491
TI  - Oxyneurography: A non-invasive NIRS technique to measure nerve oxygenation.

PMID- 29174492
TI  - Optimal use of EEG montages to identify inferior temporal epileptiform activity.

PMID- 29174493
TI  - Surgical resection versus transarterial chemoembolization for BCLC intermediate
      stage hepatocellular carcinoma: a systematic review and meta-analysis.
AB  - BACKGROUND & OBJECTIVE: Transarterial chemoembolization (TACE) is recommended as
      the first-line therapy for intermediate stage hepatocellular carcinoma (HCC)
      according to the Barcelona Clinic Liver Cancer (BCLC) algorithm. However, in
      clinical practice, many such patients undergo surgical resection. A meta-analysis
      with a systematic search of the medical literature was conducted to compare these
      two procedures for BCLC intermediate stage HCC. METHODS: PubMed, Embase, Medline
      and Cochrane library were searched for studies comparing surgical resection with
      TACE for BCLC intermediate stage HCC that were published before December 2016.
      The primary outcome was overall survival, and the secondary outcomes were
      postoperative complications and 30-day mortality. RESULTS: This meta-analysis
      included 9 studies with 2619 patients (surgical resection, n = 1204 (46%) and
      TACE, n = 1415 (54%)). When compared with the TACE group, the pooled hazard ratio
      (HR) for the 1, 3 and 5-year OS rates in patients who underwent surgical
      resection were 0.62 (95% CI 0.51-0.75, P = 0.39; I2 = 6%, P < 0.001), 0.58 (95%
      CI 0.51-0.67, P = 0.25; I2 = 22%, P < 0.001) and 0.59 (95% CI 0.54-0.64, P =
      0.18; I2 = 20%, P < 0.001). No significant differences in the pooled odds ratios
      (OR) were found between surgical resection and TACE in postoperative
      complications and 30-day mortality [OR 1.23 (95% CI 0.87 to 1.74, P = 0.390; I2 =
      0%, P = 0.240) and OR 1.11 (95% CI 0.60 to 2.04, P = 0.89; I2 = 0%, P = 0.740),
      respectively]. CONCLUSION: This meta-analysis on studies on Asian HCC patients
      demonstrated surgical resection had better overall survival than TACE for
      patients with intermediate stage HCC, without any significant increase in
      postoperative complication or 30-day mortality rates. Further studies are needed
      to validate these results on Western patients, moreover, a reappraisal of the
      recommended treatments for BCLC intermediate stage HCC should be considered.

PMID- 29174495
TI  - Global spread of mouse-adapted Staphylococcus aureus lineages CC1, CC15, and CC88
      among mouse breeding facilities.
AB  - We previously reported that laboratory mice from all global vendors are
      frequently colonized with Staphylococcus aureus (S. aureus). Genotyping of a snap
      sample of murine S. aureus isolates from Charles River, US, showed that mice were
      predominantly colonized with methicillin-sensitive CC88 strains. Here, we
      expanded our view and investigated whether laboratory mice from other global
      animal facilities are colonized with similar strains or novel S. aureus lineages,
      and whether the murine S. aureus isolates show features of host adaptation. In
      total, we genotyped 230 S. aureus isolates from various vendor facilities of
      laboratory mice around the globe (Charles River facilities in the USA, Canada,
      France, and Germany; another US facility) and university- or company-associated
      breeding facilities in Germany, China and New Zealand. Spa typing was performed
      to analyse the clonal relationship of the isolates. Moreover, multiplex PCRs were
      performed for human-specific virulence factors, the immune-evasion cluster (IEC)
      and superantigen genes (SAg). We found a total of 58 different spa types that
      clustered into 15 clonal complexes (CCs). Three of these S. aureus lineages had
      spread globally among laboratory mice and accounted for three quarters of the
      isolates: CC1 (13.5%), CC15 (14.3%), and CC88 (47.0%). Compared to human
      colonizing isolates of the same lineages, the murine isolates frequently lacked
      IEC genes and SAg genes on mobile genetic elements, implying long-term adaptation
      to the murine host. In conclusion, laboratory mice from various vendors are
      colonized with host-adapted S. aureus-strains of a few lineages, predominantly
      the CC88 lineage. S. aureus researchers must be cautioned that S. aureus
      colonization might be a relevant confounder in infection and vaccination studies
      and are therefore advised to screen their mice before experimentation.

PMID- 29174496
TI  - Is it safe for people with epilepsy to donate blood? A systematic review.
AB  - OBJECTIVE: In many countries people with epilepsy are temporarily or permanently
      excluded from blood donation. This exclusion is based on the assumption that they
      are more likely to experience adverse donor reactions such as epileptic seizures,
      and not on scientific evidence. A systematic review was therefore performed to
      critically examine the evidence with regard to adverse effects of blood donation
      on epilepsy patients. METHODS: Five databases (MEDLINE, Embase, The Cochrane
      Library, Web of Science and CINAHL) were searched for studies from the date of
      inception until December 2014. Two of the authors screened the articles and
      extracted the data independently and used the GRADE approach to assess the
      quality of evidence. RESULTS: The literature search yielded 7283 references.
      Following title and abstract screening in the first phase, and full text
      screening in the second phase, only three observational studies were finally
      withheld: one cohort study and two case series. None of the three studies could
      demonstrate that a blood donation resulted in adverse events in epilepsy
      patients. However, the studies were of poor methodological quality and lacked a
      solid statistical analysis. CONCLUSIONS: Limited low quality studies could not
      demonstrate that blood donors with epilepsy are at an increased risk of adverse
      events. Further research is necessary to determine whether and how long epilepsy
      patients have to be excluded from blood donation.

PMID- 29174497
TI  - Antioxidant action of grape seed polyphenols and aerobic exercise in improving
      neuronal number in the hippocampus is associated with decrease in lipid
      peroxidation and hydrogen peroxide in adult and middle-aged rats.
AB  - The present study explored the effects of swimming training and grape seed
      proanthocyanidin extract (GSPE) on neuronal survival in the hippocampus (HC) of
      middle-aged rats along with oxidative stress (OS) parameters. Further, the
      bioavailability of the GSPE, catechin, epicatechin and gallic acid were measured
      in the HC and plasma. Male Wistar rats were grouped into: sedentary control, SE
      C; swimming trained, SW-T; SE-C, supplemented sedentary, SE-C(PA) and swimming
      trainees, SW-T(PA). The supplement was a daily dose of 400mg GSPE/kg body weight.
      Swimming training lasted for 2h/day and for 14weeks. Glutathione level was
      increased in response to single and combined interventions in the middle-aged
      rats. Adult trainees showed increased glutathione peroxidase activity unlike
      middle-aged wherein increase was seen in SE-C(PA) alone. Lowered catalase
      activity with age in the HC increased in response to the combined interventions
      although single interventions were also effective. HC from both ages showed
      decrease in lipid peroxidation and hydrogen peroxide levels in response to the
      interventions. GSPE constituents were seen in the HC of swimming trained middle
      aged and adult rats. The study suggests that combined intervention is effective
      in decreasing LPO and H2O2 generation in the HC. Further, the neuronal numbers
      and planimetric volumes of CA1 pyramidal layer was significantly reduced in
      middle-aged rats compared to adults. Interestingly, both interventions enhanced
      the numbers and volumes in adult and middle-aged rats. Thus, age-associated
      decrease in CA1 neurons could be restored by both the interventions. The results
      of the present study will help in developing effective therapies for age
      associated degenerative changes and cognitive deficits.

PMID- 29174498
TI  - Response to "letter to the editor in response to "Our unrequited love for natural
      ingredients" by Burdock and Wang".

PMID- 29174494
TI  - Validation of Structures in the Protein Data Bank.
AB  - The Worldwide PDB recently launched a deposition, biocuration, and validation
      tool: OneDep. At various stages of OneDep data processing, validation reports for
      three-dimensional structures of biological macromolecules are produced. These
      reports are based on recommendations of expert task forces representing
      crystallography, nuclear magnetic resonance, and cryoelectron microscopy
      communities. The reports provide useful metrics with which depositors can
      evaluate the quality of the experimental data, the structural model, and the fit
      between them. The validation module is also available as a stand-alone web server
      and as a programmatically accessible web service. A growing number of journals
      require the official wwPDB validation reports (produced at biocuration) to
      accompany manuscripts describing macromolecular structures. Upon public release
      of the structure, the validation report becomes part of the public PDB archive.
      Geometric quality scores for proteins in the PDB archive have improved over the
      past decade.

PMID- 29174499
TI  - Preclinical evaluation of a paclitaxel-incorporated nanoparticle-coated balloon
      in rabbit and porcine models.
AB  - BACKGROUND: The main drawback of current available drug coated balloons (DCB) is
      that a certain percentage of the coated drug is lost in the bloodstream during
      its delivery to the target lesion. We integrated the nanoparticle-mediated drug
      delivery technology and polydimethylsiloxane (PDMS) as a new excipient to
      facilitate an efficient drug delivery and uptake by endothelial cells. The
      present study aimed to evaluate the efficacy of the new DCB. METHOD AND RESULTS:
      The novel DCB were coated with 5.6mg of paclitaxel-incorporated nanoparticles
      using PDMS. The efficacy of the new DCB was examined in rabbit iliac stent model
      (n=12) and in the swine in-stent restenosis model (n=8) by quantitative coronary
      angiography (QCA) and optical coherence tomography (OCT). At 28days follow-up in
      the swine in-stent restenosis model, the area stenosis was significantly lower in
      DCB group as compared with that of the control group in OCT analysis (0.31+/-0.05
      vs 0.49+/-0.06, p=0.04) though there was no significant differences observed in
      the rabbit iliac stent model in QCA and OCT analysis. CONCLUSION: The study
      results indicated that the paclitaxel-incorporated nanoparticle-coated balloon
      using PDMS has an inhibitory effect for the proliferation of smooth muscle cell
      in a swine coronary in-stent restenosis model.

PMID- 29174500
TI  - Long-term results of a sirolimus-eluting stent with biodegradable polymer
      (RAPSTROMTM) in de novo coronary stenoses.
AB  - OBJECTIVES: To report long-term results of a novel sirolimus-eluting stent with
      biodegradable polymer BACKGROUND: Newer generation drug-eluting stents are
      characterized by thin struts, improved platform design and highly biocompatible
      polymer carrying the antiproliferative drug. The RapstromTM stent, sharing these
      features, showed promising outcomes in preclinical models and in a first-in-man
      trial. METHODS: The present study is a multicenter, non-randomized post-market
      registry, including patients with de novo coronary artery disease treated with
      implantation of one or more Rapstrom stents. Primary endpoint of the study was
      the rate of major adverse cardiac events (MACE) at three-year follow-up. RESULTS:
      1073 patients were enrolled, with a high prevalence of diabetes (35%) and acute
      coronary syndrome at presentation (82%); at three-year follow up, MACE rate was
      14.8%, with a low incidence of definite or probable stent thrombosis (0.75%).
      CONCLUSIONS: These data confirm the good clinical performance of the Rapstrom
      stent, supporting the concept that the combination of thin struts and
      biodegradable polymer is associated with positive clinical outcomes.

PMID- 29174501
TI  - Active Surveillance for Low and Intermediate Risk Prostate Cancer: Opinions of
      North American Genitourinary Oncology Expert Radiation Oncologists.
AB  - INTRODUCTION: The ProtecT trial has provided level 1 evidence supporting active
      surveillance for prostate cancer patients with low-risk and intermediate-risk
      disease. The effect of these findings on the opinions of North American
      genitourinary (GU) experts regarding the role of active surveillance for these
      patients has not been previously examined. MATERIALS AND METHODS: A survey was
      distributed to 88 practicing North American GU physicians serving on decision
      making committees of cooperative group research organizations. Questions
      pertained to appropriateness of active surveillance in patients with low-risk and
      intermediate-risk (Gleason 3+4) disease. Opinions regarding active surveillance
      were correlated with practice patterns using Fisher exact test. RESULTS: Forty
      two radiation oncologists completed the survey. Forty percent had been in
      practice for more than 20 years; 90% practice at an academic center. Forty-five
      percent see >= 20 patients per month in consultation. More than 95% (40 of 42)
      recommended active surveillance for Gleason 6 disease, whereas only 17%
      recommended active surveillance for Gleason 3+4 disease. There were no
      demographic differences between supporters or opponents regarding active
      surveillance with regard to monthly patient volume, practice type, likelihood of
      self-identifying as an expert brachytherapist, belief in advanced imaging
      techniques, or preferred default external beam radiation therapy
      dose/fractionation for either low-risk or intermediate-risk disease. However,
      there was a trend toward greater support of active surveillance for Gleason 3+4
      disease among experts having practiced < 10 years versus >= 10 years (P = .085).
      CONCLUSION: Active surveillance is almost universally supported by North American
      GU expert radiation oncologists for low-risk prostate cancer. However, there is
      very weak support for this strategy in Gleason 3+4 disease despite the ProtecT
      trial providing level 1 evidentiary support in both risk groups. There were no
      significant differences between experts supporting versus opposing active
      surveillance for either low-risk or intermediate-risk disease. These preferences
      might affect the design of future clinical studies, influencing the adoption of
      active surveillance in North American clinical practice.

PMID- 29174502
TI  - Lymph Node Response in a Patient With Metastatic Castration-resistant Prostate
      Cancer Treated With Radium-223.

PMID- 29174503
TI  - External Validation of the Arterial-Based Complexity Score and First Head-to-Head
      Comparison With the R.E.N.A.L. and PADUA Scores and C-index.
AB  - INTRODUCTION: We performed an external validation of the arterial-based
      complexity (ABC) score using a head-to-head comparison with the R.E.N.A.L.
      (radius, exophytic/endophytic tumor properties, nearness of tumor to deepest
      portion of collecting system or sinus, anterior/posterior descriptor, location
      relative to the polar line), PADUA (preoperative aspects and dimension for
      anatomic classification of renal tumors), and C-index scores for the prediction
      of surgical outcomes after partial nephrectomy. MATERIALS AND METHODS: The data
      from a series of consecutive open or robot-assisted partial nephrectomies
      performed from January 2014 to July 2016 by 4 expert surgeons at a tertiary
      academic institution were reviewed. After dedicated training, 1 urologist not
      involved in the surgical procedures evaluated the cross-sectional imaging studies
      and assigned the nephrometry score using the 4 nephrometry scoring systems. The
      predictive performance of the ABC and other scoring systems was tested in
      univariate and multivariable fashion. RESULTS: Overall, 234 patients were
      recruited (148 men and 86 women; age, 63 +/- 10.9 years). The scores were all
      related to the estimated blood loss, use of hilar clamping, ischemia time,
      operative time, length of stay, and MIC (margin status, ischemia time,
      complications) score. They were not related to the occurrence of postoperative
      complications or, for the C-index and ABC score, the length of stay. In a head-to
      head comparison, the ABC was not inferior only to the C-index relative to the
      occurrence of complications and MIC score, with borderline statistical
      significance. On multivariate analysis, the ABC score provided significant
      improvement only for the prediction of the operative and ischemia times. However,
      its performance was inferior to that of the other scoring systems. In addition,
      only the PADUA score improved the prediction of artery clamping and MIC score,
      and only the R.E.N.A.L. score showed an advantage for the prediction of the
      estimated blood loss. CONCLUSION: The predictive ability of ABC was inferior to
      that of well-established existing nephrometry scoring systems, such as the PADUA
      and R.E.N.A.L. scores.

PMID- 29174504
TI  - Intravesical Immunomodulatory Imiquimod Enhances Bacillus Calmette-Guerin
      Downregulation of Nonmuscle-invasive Bladder Cancer.
AB  - BACKGROUND: The Toll-like receptor (TLR)2/4 agonist bacillus Calmette-Guerin
      (BCG), although not failure proof, has been the most efficient immunomodulatory
      treatment of immunogenic nonmuscle-invasive bladder cancer (NMIBC) for > 40
      years. We investigated the role of the immunomodulatory molecule TLR7 agonist
      imiquimod through the BCG key receptors TLR2/4 and the main downstream molecules
      of the mammalian target of rapamycin pathway in NMIBC treatment. MATERIALS AND
      METHODS: A total of 40 Fischer-344 rats, 7 weeks old, received 4 doses of 1.5
      mg/kg N-methyl-N-nitrosourea intravesically on weeks 0, 2, 4, and 6 for cancer
      induction. At week 8, the rats were randomized into 4 groups (10 per group) and
      treated intravesically once a week for 6 weeks: control (0.2 mL of vehicle); BCG
      (2 * 106 colony-forming units Connaught strain in 0.2 mL); imiquimod (20 mg/kg in
      0.2 mL), and associated treatment BCG plus imiquimod in 0.2 mL. The bladders were
      extracted and analyzed for histopathology, immunohistochemistry, cell
      proliferation (Ki-67), apoptosis (terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling [TUNEL]), and immunoblotting for
      TLR2, TLR4, p-P70S6K, and p-4E-BP1 proteins. RESULTS: The histopathology results
      showed that BCG and imiquimod decreased bladder tumorigenesis compared with the
      control group, with a proliferation decrease (Ki-67) and an apoptosis increase
      (TUNEL). BCG upregulated TLR2/4, imiquimod upregulated TLR4, and both
      downregulated P70S6K1. CONCLUSION: Imiquimod is able to efficiently decrease
      bladder carcinogenesis through upregulation of TLR7/4 and downregulation of
      P70S6K1 protein, generating new perspectives to boost BCG effects in the future.

PMID- 29174505
TI  - Protective effect of quercetin and rutin encapsulated liposomes on induced
      oxidative stress.
AB  - Natural antioxidants show many pharmacological properties, but poor solubility
      and inability to cross cell membrane. Liposomes are biocompatible and
      phospholipid vesicles able to carry hydrophilic, hydrophobic, and amphiphilic
      molecules. This paper focus on the synthesis of anionic, cationic and
      zwitterionic liposomes, loaded with quercetin or rutin, and on the evaluation of
      their cytotoxicity and protective effects against oxidative stress. Chemical
      characterization was obtained by dynamic light scattering and z-potential
      experiments. In vitro cell behavior was evaluated by Neutral Red Uptake test. All
      liposomes, empty and loaded with antioxidants, are stable. The cytotoxicity of
      both quercetin and rutin encapsulated in zwitterionic and anionic liposomes is
      higher than that of their solutions. Quercetin and rutin loaded in cationic
      liposomes are able to inhibit the toxic effect of empty liposomes. The
      encapsulation of rutin at 5.0*10-5 and 5.0*10-4M, in zwitterionic and anionic
      liposomes, protects fibroblasts by H2O2 treatment, while the loading with
      quercetin does not have effect on improving cell viability. All data suggest that
      the tested liposomes are stable and able to include quercetin and rutin. The
      liposomes encapsulation of antioxidants makes easier their internalization by
      cells. Moreover, zwitterionic and anionic liposomes loaded with rutin protect
      cells by oxidative stress. Liposomes stability together with their good in vitro
      cytocompatibility, both empty and loaded with antioxidant molecules, makes these
      systems suitable candidates as drug delivery systems. Moreover, the encapsulation
      of rutin, is able to protect cells by oxidative stress.

PMID- 29174506
TI  - Discovery of novel purine nucleoside derivatives as phosphodiesterase 2 (PDE2)
      inhibitors: Structure-based virtual screening, optimization and biological
      evaluation.
AB  - Phosphodiesterase 2 (PDE2) has received much attention for the potential
      treatment of the central nervous system (CNS) disorders and pulmonary
      hypertension. Herein, we identified that clofarabine (4), an FDA-approved drug,
      displayed potential PDE2 inhibitory activity (IC50 = 3.12 +/- 0.67 MUM) by
      structure-based virtual screening and bioassay. Considering the potential
      therapeutic benefit of PDE2, a series of purine nucleoside derivatives based on
      the structure and binding mode of 4 were designed, synthesized and evaluated,
      which led to the discovery of the best compound 14e with a significant
      improvement of inhibitory potency (IC50 = 0.32 +/- 0.04 MUM). Further molecular
      docking and molecular dynamic (MD) simulations studies revealed that 5'-benzyl
      group of 14e could interact with the unique hydrophobic pocket of PDE2 by forming
      extra van der Waals interactions with hydrophobic residues such as Leu770,
      Thr768, Thr805 and Leu809, which might contribute to its enhancement of PDE2
      inhibition. These potential compounds reported in this article and the valuable
      structure-activity relationships (SARs) might bring significant instruction for
      further development of potent PDE2 inhibitors.

PMID- 29174507
TI  - N-Arylsulfonylsubstituted-1H indole derivatives as small molecule dual inhibitors
      of signal transducer and activator of transcription 3 (STAT3) and tubulin.
AB  - Signal transducer and activator of transcription (STAT3) is a proposed
      therapeutic target for the development of anti-cancer agents. In this report, a
      series of N-arylsulfonylsubstituted-1H indole derivatives were designed and
      synthesized as STAT3 inhibitors, their anti-proliferative activities were
      evaluated against a number of tumor cells, some potent compounds exhibited IC50
      values less than 10 MUM. The most potent compound 4a was further confirmed to
      inhibit STAT3 phosphorylation at Tyr705. It was further revealed that 4a arrested
      the cell cycle at the G2/M phase and inhibited tubulin polymerization. This study
      describes a series of N-arylsulfonylsubstituted-1H indole derivatives as potent
      anti-cancer agents targeting both STAT3 and tubulin.

PMID- 29174508
TI  - Microwave-assisted diastereoselective two-step three-component synthesis for
      rapid access to drug-like libraries of substituted 3-amino-beta-lactams.
AB  - Large, diverse compound libraries are an essential requisite in target-based drug
      development. In this work, a robust microwave-assisted synthesis for the
      diastereoselective generation of 3-saccharinyl-trans-beta-lactams is reported.
      The method is optimised for combinatorial library synthesis in which decoration
      of the scaffold is varied on both the beta-lactam and the saccharine moiety.
      Within the European Lead Factory (ELF) consortium, a library of 263 compounds was
      efficiently produced using the developed methodology.

PMID- 29174509
TI  - TLR8 activation and inhibition by guanosine analogs in RNA: Importance of
      functional groups and chain length.
AB  - Toll-like receptor 8 (TLR8) is an important component of the human innate immune
      system that recognizes single stranded RNA (ssRNA). Recent X-ray crystal
      structures of TLR8 bound to ssRNA revealed a previously unrecognized binding site
      for a 5'-UpG-3' dinucleotide. Here we use an atomic mutagenesis strategy coupled
      with a cellular TLR8 activation assay to probe the importance of specific
      functional groups present on the guanine base in RNA-mediated receptor agonism
      and antagonism. Results from RNA analogs containing 7-deazaguanosine, 2
      aminopurine and inosine confirm the importance of guanine N7, O6 and N2,
      respectively, in TLR8 activation. Nevertheless, these RNAs each retained TLR8
      antagonism activity. RNA containing 7-deaza-8-azainosine (7d8aI) was prepared
      from a novel phosphoramidite and found to be a weaker TLR8 activator than
      guanosine-containing RNA. However, 7d8aI-containing RNA also retained TLR8
      antagonism activity indicating that removal of multiple TLR8 H-bonding sites on
      guanine is insufficient for blocking TLR8 antagonism by guanine-containing RNA.
      We also identified an oligoribonucleotide length dependence on both TLR8
      activation and antagonism. These studies extend our understanding of the effects
      of nucleobase modification on immune stimulation and will inform the design of
      novel RNA-based therapeutics.

PMID- 29174510
TI  - Bioluminescence probe for gamma-glutamyl transpeptidase detection in vivo.
AB  - To detect gamma-Glutamyl Transpeptidase (GGT) activity in vitro and in vivo, a
      bioluminescence probe with high sensitivity and specificity was well designed and
      synthesized. This probe can be recognized by GGT and release strong
      bioluminescence with its further reaction with luciferase. The performance of
      this probe was demonstrated in vitro and in cells. Finally, we applied the probe
      for detection of GGT activity in xenograft model.

PMID- 29174511
TI  - Cardiorespiratory Fitness and Health Outcomes: A Call to Standardize Fitness
      Categories.
AB  - An inverse association between physical activity or fitness status and health
      outcomes has been reported by several cohort studies. When fitness categories are
      established in quartiles or quintiles based on the peak exercise capacity
      achieved, the association is graded. Although significant health benefits of
      increased cardiorespiratory fitness (CRF) have been uniformly reported, the
      degree of protection has varied substantially between studies. This variability
      is likely due to varying methods used to define CRF categories, and not
      considering age, despite its strong effect on CRF. To ameliorate these
      methodological discrepancies, we propose standardized guidelines by which age
      specific CRF categories should be defined.

PMID- 29174512
TI  - Biosynthesis of selenium-nanoparticles and -nanorods as a product of selenite
      bioconversion by the aerobic bacterium Rhodococcus aetherivorans BCP1.
AB  - The wide anthropogenic use of selenium compounds represents the major source of
      selenium pollution worldwide, causing environmental issues and health concerns.
      Microbe-based strategies for metal removal/recovery have received increasing
      interest thanks to the association of the microbial ability to detoxify toxic
      metal/metalloid polluted environments with the production of nanomaterials. This
      study investigates the tolerance and the bioconversion of selenite (SeO32-) by
      the aerobically grown Actinomycete Rhodococcus aetherivorans BCP1 in association
      with its ability to produce selenium nanoparticles and nanorods (SeNPs and
      SeNRs). The BCP1 strain showed high tolerance towards SeO32- with a Minimal
      Inhibitory Concentration (MIC) of 500mM. The bioconversion of SeO32- was
      evaluated considering two different physiological states of the BCP1 strain, i.e.
      unconditioned and/or conditioned cells, which correspond to cells exposed for the
      first time or after re-inoculation in fresh medium to either 0.5 or 2mM of
      Na2SeO3, respectively. SeO32- bioconversion was higher for conditioned grown
      cells compared to the unconditioned ones. Selenium nanostructures appeared
      polydisperse and not aggregated, as detected by electron microscopy, being
      embedded in an organic coating likely responsible for their stability, as
      suggested by the physical-chemical characterization. The production of smaller
      and/or larger SeNPs was influenced by the initial concentration of provided
      precursor, which resulted in the growth of longer and/or shorter SeNRs,
      respectively. The strong ability to tolerate high SeO32- concentrations coupled
      with SeNP and SeNR biosynthesis highlights promising new applications of
      Rhodococcus aetherivorans BCP1 as cell factory to produce stable Se
      nanostructures, whose suitability might be exploited for biotechnology purposes.

PMID- 29174513
TI  - Nutrient removal from hydroponic wastewater by a microbial consortium and a
      culture of Paracercomonas saepenatans.
AB  - The potential of microbial processes for removal of major nutrients (e.g., N, P)
      and inorganic cations (e.g., Ca2+, Mg2+, and Fe2+) from hydroponic systems was
      investigated. Microbial consortium- and axenic culture-based experiments were
      conducted in a waste nutrient solution (WNS). A microbial consortium grown in the
      WNS and selected microalgae species of Paracercomonas saepenatans were inoculated
      in two different synthetic media (Bold's Basal Medium (BBM) and synthetic WNS) in
      batch systems, and the microbial growth characteristics and the rate and extent
      of nutrient removal were determined for each system. No toxicity or growth
      inhibition was observed during microbial growth in either media. Both the waste
      nutrient-grown microbial consortium and Paracercomonas saepenatans can be grown
      effectively in BBM and WNS, and both remove most ions from both media (e.g.,>99%
      removal of NO3- and 41-100% removal of PO43-) within 16days. Significant nutrient
      removal was observed during the growth phase of the microbial communities (4
      10days period), indicating major nutrient utilization for microbial growth as
      well as chemical mineral precipitation. Furthermore, MINEQL+4.6 modeling showed
      higher PO43- removal in WNS during microbial growth (compared to BBM) due to
      precipitation of phosphate minerals (e.g., hydroxyapatite, vivianite). The
      dominant microbial species in both systems were also identified. DNA sequencing
      showed that Vorticella (58%) and Scenedesmus (33%) in WNS and Scenedesmus (89%)
      in BBM were the predominant species. This study demonstrates the potential
      application of microbial consortium (predominantly algae and protozoan)-based
      treatment techniques for hydroponic systems.

PMID- 29174514
TI  - Multi-spectral imaging for the estimation of shooting distances.
AB  - Multispectral images of clothing targets shot at seven different distances (from
      10 to 220cm) were recorded at 18 specific wavelengths in the 400-1000nm range to
      visualize the gunshot residue (GSR) pattern. Principal component analysis (PCA)
      showed that the use of violet-blue wavelengths (430, 450 and 470nm) provided the
      largest contrast between the GSR particles and the white cotton fabric. Then, the
      correlation between the amount of GSR particles on clothing targets and the
      shooting distance was studied. By selecting the blue frame of multispectral
      images (i.e. the blue frame in the red-green-blue (RGB) system which falls at
      470nm), the amount of pixels containing GSR particles was accounted based on the
      intensity of pixels in that frame. Results demonstrated that the number of pixels
      containing GSR exponentially decreases with the shooting distance from 30 to
      220cm following a particular exponential equation. However, the targets shot at
      the shortest distance (10cm) did not satisfy the above equation, probably due to
      the noticeable differences of the GSR-pattern of these targets (e.g. high
      presence of soot). Then, the equation was applied to validation samples to
      estimate the shooting distances, obtaining results with an error below 10%.

PMID- 29174515
TI  - Comparison and evaluation of the quick purification methods of methamphetamine
      hydrochloride from dimethyl sulfone for spectroscopic identification.
AB  - Methods to quickly purify methamphetamine hydrochloride from the cutting agent
      dimethyl sulfone for subsequent identification of confiscated crystalline samples
      using infrared absorption spectroscopy were compared and evaluated. Although
      sequential solvation and reprecipitation methods were simple, spectral
      contamination from dimethyl sulfone was inevitable and might affect the
      interpretation of the spectra. In addition, methamphetamine hydrochloride and
      dimethyl sulfone could form a solid solution because of solvation of both
      crystals into a single solution layer. By contrast, sublimation was an effective
      method for separation of methamphetamine hydrochloride and dimethyl sulfone.
      Sublimation combined with infrared absorption spectroscopy enabled rapid
      identification of crystalline methamphetamine hydrochloride.

PMID- 29174516
TI  - RETRACTED: Delayed Hemolytic Transfusion Reaction and Hyperhemolysis Syndrome
      without Detectable Alloantibodies or Autoantibodies in a Patient with Sickle Cell
      Disease: A Fatal Case Report and Literature Review.
AB  - L'editeur a le regret de vous informer que cet article a deja ete publie dans:
      Journal of Blood Disorders & Transfusion, 2017, 8:4. DOI: 10.4172/2155
      9864.1000388. Cette seconde publication faite par erreur a ete retiree.

PMID- 29174517
TI  - Longitudinal associations of the alternative and terminal pathways of complement
      activation with adiposity: The CODAM study.
AB  - OBJECTIVE: To investigate longitudinal associations of components of the
      alternative (C3, C3a, Bb, factor D [FD], factor H [FH], and properdin) and the
      terminal complement pathway (C5a, sC5b-9) with adiposity. METHODS: A prospective
      human cohort study (n=574 at baseline, n=489 after 7 years follow-up) was
      analyzed. Generalized estimating equations were used to evaluate the longitudinal
      associations between complement components (standardized values) and adiposity
      (main outcome BMI [kg/m2]). Multiple linear regression models were used to
      investigate the associations between change in complement levels and change in
      BMI. Analyses were adjusted for age, sex, medication and lifestyle. RESULTS: Over
      the 7-year period, baseline C3 was positively associated with BMI (beta=1.72 [95%
      confidence interval (CI): 1.35; 2.09]). Positive associations were also observed
      for C3a (beta=0.64 [0.31; 0.97]), FD (beta=1.00 [0.59; 1.42]), FH (beta=1.17
      [0.82; 1.53]), and properdin (beta=0.60 [0.28; 0.92]), but not for Bb, C5a or
      sC5b-9. Moreover, changes in C3 (beta=0.52 [0.34; 0.71]) and FH (beta=0.51 [0.32;
      0.70]) were significantly associated with changes in BMI. CONCLUSIONS: The
      complement system, particularly activation of the alternative pathway, may be
      involved in development of adiposity. Whether individual aspects of alternative
      pathway activation have a causal role in human obesity, remains to be
      investigated.

PMID- 29174518
TI  - The anterolateral thigh flap with kiss technique for microsurgical reconstruction
      of oncological scalp defects.

PMID- 29174519
TI  - Importance of sentinel lymphatic node biopsy in detection of early
      micrometastases in patients with cutaneous squamous cell carcinoma.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is the second most common
      malignant skin cancer with a tendency to spread through the lymphogenic pathway.
      Metastases are found in 2-6% of cases. The aim of this study was to determine
      CSCC micrometastases when non-invasive examination methods do not detect them.
      METHOD: A total of 88 patients were included in the study with clinically
      diagnosed, histologically confirmed CSCC and no distant or regional lymph node
      metastases detected during instrumental tests. The patients were grouped into low
      and high-risk CSCC groups. They underwent one-stage surgery - radical tumour
      excision and sentinel lymph node/nodes biopsy (SLNB). Significance level of 0.05
      was chosen for testing statistical hypotheses. RESULTS: One hundred and fifty
      three sentinel lymph nodes (SLNs) were detected and excised in 88 patients.
      Micrometastases were found in five SLNs of three patients with high-risk CSCC.
      The rate of micrometastases was 3.4%; however, in the high-risk group it was
      6.5%. The mean diameter of CSCC with micrometastases in SLN was 5.6 +/- 3.5 cm,
      and that without micrometastases was 1.5 +/- 1.1 cm (p = 0.003). The depth of
      CSCC according to Breslow in the patients with detected micrometastases in SLN
      was 3.5 +/- 1.2 mm, and that without detected micrometastases was 2.2 +/- 1.4 mm
      (p = 0.047). Patients with micrometastases in sentinel lymphatic nodes underwent
      radical lymphadenectomy. There was neither recurrence of CSCC metastases in
      regional lymph nodes nor distant metastases during the research period detected.
      CONCLUSIONS: In patients with CSCC the rate of micrometastases directly
      correlates with the depth and diameter of the tumour. In patients with high-risk
      CSCC the rate of micrometastases is 6.5%.

PMID- 29174521
TI  - Influence of recent altitude exposure on sea level sympathetic neural &
      hemodynamic responses to orthostasis.
AB  - Although it has been shown that muscle sympathetic nerve activity increases
      during high altitude exposure, mechanisms of sympathoexcitation and blood
      pressure control after return from altitude are not well described. We
      hypothesized that: (1) living for 12days at 4300m (Pikes Peak, Colorado) would
      result in increased muscle sympathetic nerve activity 24h after return to sea
      level; (2) post-Pikes Peak sympathetic neural and hemodynamic responses to
      orthostasis would be decreased due to a potential 'ceiling effect' on sympathetic
      activity; and (3) the magnitude of individual increases in sympathetic nerve
      activity post-Pikes Peak would be inversely related to baseline sympathetic nerve
      activity before traveling to altitude. Muscle sympathetic nerve activity, heart
      rate and blood pressure were measured in 9 healthy individuals (24+/-8years) in
      supine, 30 degrees  and 45 degrees  head-up tilt positions. Measurements were
      conducted twice at sea level, once before (pre-Pikes Peak) a 12day residence at
      4300m, and once within 24h of return (post-Pikes Peak). Supine muscle sympathetic
      nerve activity was higher (post: 27+/-5 vs pre: 17+/-6bursts/min) upon return
      from altitude (p<0.05). Individual values for pre-Pikes Peak sympathetic activity
      were inversely related to post-altitude sympathoexcitation (r=-0.69, p<0.05).
      There were no differences in neural or cardiovascular responses to tilt between
      pre and post- Pikes Peak (p>0.05). We conclude that 12days' residence at 4300m
      causes a sustained sympathoexcitation which does not impair the ability of muscle
      sympathetic nerves to respond appropriately to orthostasis.

PMID- 29174520
TI  - Liver Dysfunction during Pregnancy and Its Association of With Preterm Birth in
      China: A Prospective Cohort Study.
AB  - BACKGROUND: Liver dysfunction is common in pregnancy but its association with
      adverse pregnancy outcomes such as preterm birth (PTB) remains unclear. METHODS:
      A prospective cohort of HBV-infected or uninfected pregnant women attending
      antenatal care was recruited at Nantong Maternal and Child Health Hospital
      between January 1, 2012, and June 30, 2016. Liver function tests (LFTs) were
      monitored through pregnancy. The primary outcomes were PTB and very PTB (delivery
      prior 37 and 32weeks' gestation respectively). Poisson regression was used to
      estimate adjusted risk ratios (RR) for women with HBV infection and LFT
      abnormalities. RESULTS: Among 36,755 pregnant women (1,113 HBV carriers and
      35,642 non-HBV subjects), 3,519 (9.57%) had abnormal LFTs. The commonest cause
      for liver dysfunction during pregnancy was non-alcoholic fatty liver diseases
      (NAFLD, 51.3%). Abnormal aspartate aminotransferase (AST), gamma
      glutamyltransferase (GGT) and two folds upper limit of normal total bilirubin (RR
      and 95%CI: 2.73, 1.30-5.76; 2.24, 1.35-3.31; 2.01, 1.22-3.31 respectively),
      rather than HBsAg positivity, were identified as independent risk factors for
      preterm birth. Besides, GGT abnormality was associated with increased risk of
      very PTB. CONCLUSIONS: We suggest that surveillance of LFTs among pregnant women
      should be warranted, given the increased risk of PTB.

PMID- 29174522
TI  - [Differences in the management of patients with atrial fibrillation according to
      whether primary care or the specialist initiates treatment with direct oral
      anticoagulants. The SILVER-AP and BRONCE-AP studies].
AB  - OBJECTIVES: To determine the clinical characteristics and management of patients
      with non-valvular atrial fibrillation (NVAF) treated with direct oral
      anticoagulants (DOAC) according to who initiates their prescription, the Primary
      Care (PC) physician or referring the patient to a specialist. MATERIAL AND
      METHODS: Two observational, cross-sectional and multicentre studies were compared
      for this purpose. The SILVER-AP study was performed in those autonomous
      communities in which the PC physician can prescribe DOAC directly, and the BRONCE
      AP study in those autonomous communities in which the PC physician has to refer
      the patient to the specialist to start treatment with DOAC. Patients on chronic
      treatment with anticoagulants, in whom therapy was changed, and those that were
      on current treatment with DOAC for at least 3months, were included. RESULTS: A
      total of 1,036 patients (790 from SILVER-AP study and 246 from BRONCE-AP study)
      were included. Compared with the BRONCE-AP study, those patients included in
      SILVER-AP were older and had more comorbidities, as well as a higher
      thromboembolic and haemorrhagic risk (CHA2DS2-VASc 4.3+/-1.6 vs. 3.8+/-1.8;
      P<.001; HAS-BLED 2.1+/-0.8 vs. 1.8+/-1.0; P<.001). Therapeutic adherence and
      satisfaction with treatment were high. Low doses of DOAC were frequently
      prescribed, particularly with dabigatran. CONCLUSIONS: Those patients in whom the
      PC physician can prescribe DOAC directly have a worse clinical profile, as well
      as a higher thromboembolic and haemorrhagic risk than those patients in whom the
      PC physician has to refer to the specialist.

PMID- 29174523
TI  - Transvenous Coil Embolization for the Treatment of Carotid Cavernous Fistula
      after Pipeline Placement: A Case Report.
AB  - The Pipeline embolization device (PED), a type of flow diverter, has become an
      appealing alternative treatment option for large or giant and wide-necked
      intracranial aneurysms. Carotid cavernous fistula (CCF) resulting from delayed
      aneurysmal rupture is a rare complication of PED placement with unknown
      pathophysiology. Here, we describe a case of CCF resulting from aneurysmal
      rupture following PED placement, and present the details of treatment by
      transvenous coil embolization. An 81-year-old woman was referred to our hospital
      for treatment of an 18.0 * 10.3 mm intracranial aneurysm located in the cavernous
      segment of the left internal carotid artery, noted during an examination of her
      diplopia. Endovascular treatment was conducted by positioning a single PED (4.75
      * 25 mm) across the neck of the aneurysm. The postoperative course was
      uneventful, and the patient was discharged 8 days post procedure. On post
      procedure day 10, her left oculomotor nerve palsy had worsened and she had
      developed left abducens nerve palsy, left exophthalmos, and left chemosis.
      Angiography demonstrated left direct CCF because of rupture of the aneurysm that
      had been treated with PED. Transvenous coil embolization was performed on post
      procedure day 11 to treat the CCF, and complete resolution of the CCF and
      significant thrombus formation within the aneurysm sac were confirmed 11 days
      after the second procedure. Our angiographic results suggest that the aneurysmal
      rupture was caused by aneurysmal volume expansion associated with PED-induced
      thrombosis. Transvenous coil embolization for the treatment of CCF following PED
      placement constitutes a new challenge.

PMID- 29174524
TI  - Engineering cell wall synthesis mechanism for enhanced PHB accumulation in E.
      coli.
AB  - The rigidity of bacterial cell walls synthesized by a complicated pathway limit
      the cell shapes as coccus, bar or ellipse or even fibers. A less rigid bacterium
      could be beneficial for intracellular accumulation of poly-3-hydroxybutyrate
      (PHB) as granular inclusion bodies. To understand how cell rigidity affects PHB
      accumulation, E. coli cell wall synthesis pathway was reinforced and weakened,
      respectively. Cell rigidity was achieved by thickening the cell walls via
      insertion of a constitutive gltA (encoding citrate synthase) promoter in front of
      a series of cell wall synthesis genes on the chromosome of several E. coli
      derivatives, resulting in 1.32-1.60 folds increase of Young's modulus in
      mechanical strength for longer E. coli cells over-expressing fission ring FtsZ
      protein inhibiting gene sulA. Cell rigidity was weakened by down regulating
      expressions of ten genes in the cell wall synthesis pathway using CRISPRi,
      leading to elastic cells with more spaces for PHB accumulation. The regulation on
      cell wall synthesis changes the cell rigidity: E. coli with thickened cell walls
      accumulated only 25% PHB while cell wall weakened E. coli produced 93% PHB.
      Manipulation on cell wall synthesis mechanism adds another possibility to
      morphology engineering of microorganisms.

PMID- 29174525
TI  - Clinical phenotypes and trajectories of disease progression in type 1 spinal
      muscular atrophy.
AB  - The advent of clinical trials has highlighted the need for natural history
      studies reporting disease progression in type 1 spinal muscular atrophy. The aim
      of this study was to assess functional changes using the Children's Hospital of
      Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scale in a
      cohort of type 1 infants. Nutritional and respiratory longitudinal data were also
      recorded. Patients were classified according to the severity of the phenotype and
      age of onset. SMN2 copies were also assessed. Twenty patients were included,
      eight with early onset most severe phenotype, eight with the more typical type 1
      phenotype and 4, who achieved some head control, with a milder phenotype. Both
      baseline values and trajectories of progression were different in the three
      subgroups (p = 0.0001). Infants with the most severe phenotype had the lowest
      scores (below 20) on their first assessment and had the most rapid decline. Those
      with the typical phenotype had scores generally between 20 and 40 and also had a
      fast decline. The infants with the milder phenotype had the highest scores,
      generally above 35, and a much slower deterioration. Infants with three SMN2
      copies had an overall milder phenotype and milder progression while two SMN2
      copies were found in all three subgroups.

PMID- 29174526
TI  - Timed function tests, motor function measure, and quantitative thigh muscle MRI
      in ambulant children with Duchenne muscular dystrophy: A cross-sectional
      analysis.
AB  - The development of new therapeutic agents for the treatment of Duchenne muscular
      dystrophy has put a focus on defining outcome measures most sensitive to capture
      treatment effects. This cross-sectional analysis investigates the relation
      between validated clinical assessments such as the 6-minute walk test, motor
      function measure and quantitative muscle MRI of thigh muscles in ambulant
      Duchenne muscular dystrophy patients, aged 6.5 to 10.8 years (mean 8.2, SD 1.1).
      Quantitative muscle MRI included the mean fat fraction using a 2-point Dixon
      technique, and transverse relaxation time (T2) measurements. All clinical
      assessments were highly significantly inter-correlated with p < 0.001. The
      strongest correlation with the motor function measure and its D1-subscore was
      shown by the 6-minute walk test. Clinical assessments showed no correlation with
      age. Importantly, quantitative muscle MRI values significantly correlated with
      all clinical assessments with the extensors showing the strongest correlation. In
      contrast to the clinical assessments, quantitative muscle MRI values were highly
      significantly correlated with age. In conclusion, the motor function measure and
      timed function tests measure disease severity in a highly comparable fashion and
      all tests correlated with quantitative muscle MRI values quantifying fatty muscle
      degeneration.

PMID- 29174527
TI  - Genotypic and phenotypic spectrum of the most common causative genes of Charcot
      Marie-Tooth disease in Hungarian patients.
AB  - Charcot-Marie-Tooth neuropathy (CMT) is a genetically and clinically
      heterogeneous group of neuromuscular disorders with an overall prevalence of 1
      per 2500. Here we report the first comprehensive genetic epidemiology study of
      Hungarian CMT patients. 409 CMT1 and 122 CMT2 patients were enrolled and genetic
      testing of PMP22, GJB1, MPZ, EGR2 and MFN2 genes were performed routinely. NDRG1
      and CTDP1 genes were screened only for founder mutations in Roma patients.
      Causative genetic mutations were identified in 67.2% of the CMT1 and in 33.6% of
      the CMT2 cases, which indicates an overall success rate of 59.9% in the study
      population. Considering all affected individuals, alterations were most
      frequently found in PMP22 (40.5%), followed by GJB1 (9.2%), MPZ (4.5%), MFN2
      (2.5%), NDRG1 (1.5%), EGR2 (0.8%) and CTDP1 (0.8%). The phenotypic spectrum and
      the disease severity of the studied patients also varied broadly. Deafness and
      autoimmune disorders were more often associated with PMP22 duplication, while
      MFN2 and GJB1 mutations were frequently present with central nervous system
      abnormalities. Our study may be helpful in determining the strategy of genetic
      diagnostics in Hungarian CMT patients.

PMID- 29174528
TI  - Food allergy in the developing world.

PMID- 29174529
TI  - Adjunctive azapirone for schizophrenia: A meta-analysis of randomized, double
      blind, placebo-controlled trials.
AB  - Azapirones, which are serotonin1A (5-HT1A) receptor partial agonists, have been
      used as an adjunctive treatment for schizophrenia with mixed results. This is a
      meta-analysis of the efficacy and tolerability of azapirones for schizophrenia
      based on randomized, double-blind, placebo-controlled trials (RCTs). English and
      Chinese databases were systematically and independently searched by two
      investigators. Data were extracted and analyzed using the RevMan software
      (version 5.3). Seven RCTs (n = 368) of azapirones (buspirone in 6 RCTs and
      tandospirone in 1 RCT) were identified and analyzed. Only adjunctive buspirone
      outperformed placebo regarding total psychopathology [standardized mean
      difference: -1.03 (95% confidence interval (CI): -1.91, -0.15), P = 0.02; I2 =
      92%], but the significance disappeared in sensitivity analysis after removing two
      outlying studies, and in 10 of the 12 subgroup analyses. In 5 RCTs examining
      neurocognitive function of azapirones, only 2 RCTs found the superiority of
      buspirone in improving attention/speeded motor performance, verbal and
      performance intelligence. Adjunctive buspirone outperformed placebo regarding
      extrapyramidal symptoms [SMD:-0.51, (95%CI: -0.99, -0.02), P = 0.04; I2 = 0%].
      Similar rates of discontinuation [risk ratio:1.06 (95%CI:0.54, 2.07), P = 0.86,
      I2 = 0%] and adverse drug reactions were found between both groups. Adjunctive
      buspirone and tandospirone failed to show efficacy for psychotic symptoms, but
      adjunctive buspirone may be associated with improvement in extrapyramidal
      symptoms and cognitive deficits in schizophrenia. Due to the preliminary nature
      of this meta-analysis, larger sample size and higher quality RCTs are needed to
      confirm these finding.

PMID- 29174531
TI  - Can we increase speed and efficacy of antidepressant treatments? Part I: General
      aspects and monoamine-based strategies.
AB  - Major depressive disorder (MDD) is a severe psychiatric syndrome with high
      prevalence and socioeconomic impact. Current antidepressant treatments are based
      on the blockade of serotonin (5-hydroxytryptamine, 5-HT) and/or noradrenaline
      transporters. These drugs show slow onset of clinical action and limited
      efficacy, partly due to the activation of physiological negative feed-back
      mechanisms operating through autoreceptors (5-HT1A, 5-HT1B, alpha2-adrenoceptors)
      and postsynaptic receptors (e.g., 5-HT3). As a result, clinically-relevant doses
      of reuptake inhibitors increase extracellular (active) 5-HT concentrations in the
      midbrain raphe nuclei but not in forebrain, as indicated by rodent microdialysis
      studies and by PET-scan studies in primate/human brain. The prevention of these
      self-inhibitory mechanisms by antagonists of the above receptors augments
      preclinical and clinical antidepressant effects. Hence, the mixed beta
      adrenoceptor/5-HT1A antagonist pindolol accelerated, and in some cases enhanced,
      the clinical action of selective serotonin reuptake inhibitors (SSRI). This
      strategy has been incorporated into two new multi-target antidepressant drugs,
      vilazodone and vortioxetine, which combine 5-HT reuptake inhibition and partial
      agonism at 5-HT1A receptors. Vortioxetine shows also high affinity for other 5-HT
      receptors, including excitatory 5-HT3 receptors located in cortical and
      hippocampal GABA interneurons. 5-HT3 receptor blockade by vortioxetine enhances
      pyramidal neuron activity in prefrontal cortex as well as cortical and
      hippocampal 5-HT release. It is still too soon to know whether these new
      antidepressants will represent a real advance over existing drugs in the real
      world. However, their development opened the way to future antidepressant drugs
      based on the prevention of local and distal self-inhibitory mechanisms
      attenuating monoamine activity.

PMID- 29174532
TI  - Acute kidney injury and 1-year mortality after left ventricular assist device
      implantation.
AB  - BACKGROUND: Data on the consequences of acute kidney injury (AKI) after
      continuous-flow left ventricle assist device (LVAD) implantation are scarce and
      inconsistent. In this study, we evaluated the incidence, predictors and the
      impact of AKI on mortality and renal function in the first year after LVAD
      implantation. METHODS: A retrospective, multicenter cohort study was conducted,
      including all patients (age >=18 years) undergoing LVAD implantation (91% with a
      HeartMate II device and 9% with a HeartWare device). The definition proposed by
      the Kidney Disease Improving Global Outcome (KDIGO) criteria was used to define
      AKI. RESULTS: Overall, 241 patients (mean age 52.4 +/- 12.9 years, 76% males)
      were included in the study. AKI criteria were met in 169 (70%) patients, of whom
      109 (45%) were in AKI Stage I, 22 (9%) in Stage II and 38 (16%) in Stage III. Two
      factors, the need for pre-operative inotropic support and pre-existent chronic
      kidney disease Stage <=II (estimated glomerular filtration rate [eGFR] <30
      ml/min/1.73 m2), were independently associated with the development of AKI and
      the severity of AKI stages. One-year mortality rates in patients without AKI and
      AKI Stages I, II and III were 18.7%, 26.4%, 23%, and 51%, respectively (log rank,
      p = 0.001). In the multivariable analysis, AKI Stage >=II was independently
      associated with mortality (hazard ratio 2.2 [95% confidence interval 1.1 to 4.5],
      p = 0.027) and worse renal function (beta = -7.4 [95% confidence interval -12.6
      to -2.1], p < 0.01) at 1 year. CONCLUSION: AKI is highly frequent after LVAD
      implantation. More severe AKI stages are associated with higher mortality rates
      and impaired renal function at 1 year after LVAD implantation.

PMID- 29174530
TI  - Increased cortical neuronal responses to NMDA and improved attentional set
      shifting performance in rats following prebiotic (B-GOS(r)) ingestion.
AB  - We have previously shown that prebiotics (dietary fibres that augment the growth
      of indigenous beneficial gut bacteria) such as BimunoTM galacto-oligosaccharides
      (B-GOS(r)), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat
      brain. The current investigation examined the functional correlates of these
      changes in B-GOS(r)-fed rats by measuring cortical neuronal responses to NMDA
      using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the
      attentional set-shifting task. Adult male rats were supplemented with B-GOS(r) in
      the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing.
      Cortical neuronal responses to NMDA iontophoresis, were greater (+30%) in B
      GOS(r) administered rats compared to non-supplemented controls. The intake of B
      GOS(r) also partially hindered the reduction of NMDA responses by the glycine
      site antagonist, HA-966. In the attentional set-shifting task, B-GOS(r) -fed rats
      shifted from an intra-dimensional to an extra-dimensional set in fewer trials
      than controls, thereby indicating greater cognitive flexibility. An initial
      exploration into the mechanisms revealed that rats ingesting B-GOS(r) had
      increased levels of plasma acetate, and cortical GluN2B subunits and Acetyl Co-A
      Carboxylase mRNA. These changes were also observed in rats fed daily for 3 weeks
      with glyceryl triacetate, though unlike B-GOS(r), cortical histone deacetylase
      (HDAC1, HDAC2) mRNAs were also increased which suggested an additional epigenetic
      action of direct acetate supplementation. Our data demonstrate that a pro
      cognitive effect of B-GOS(r) intake in rats is associated with an increase in
      cortical NMDA receptor function, but the role of circulating acetate derived from
      gut bacterial fermentation of this prebiotic requires further investigation.

PMID- 29174533
TI  - Impact of declining renal function on outcomes in pulmonary arterial
      hypertension: A REVEAL registry analysis.
AB  - BACKGROUND: Renal dysfunction is associated with abnormal cardiopulmonary
      hemodynamics, in-hospital death and poor survival in patients with pulmonary
      arterial hypertension (PAH), and thus it may be a prognostic biomarker. In our
      analysis we assess the relationship between change in estimated glomerular
      filtration rate (eGFR) and outcomes in PAH patients in the Registry to Evaluate
      Early and Long-term PAH Disease Management (REVEAL). METHODS: Overall 2,368
      patients were classified into chronic kidney disease (CKD) stages based on
      baseline eGFR: normal or Stages 1 or 2 (n = 1,699); Stage 3a (n = 399); Stage 3b
      (n = 196); and Stages 4 or 5 (n = 74). We evaluated the relationship between
      baseline CKD stage and survival, as well as the composite end-point of survival
      and freedom from all-cause hospitalization. The relationships between change in
      eGFR at >=1 year and these clinical end-points were also evaluated. RESULTS:
      Patients with a >=10% decline in eGFR from baseline over >=1 year had a
      significantly increased risk of death (hazard ratio 1.66; p < 0.0001) and the
      composite of all-cause hospitalization and death (hazard ratio 1.33; p = 0.002).
      This decline predicted survival independently of changes in 6-minute walk
      distance and functional class. However, a >=10% increase in eGFR was not
      significantly associated with either end-point. CONCLUSION: In REVEAL, a >=10%
      decline in eGFR over >=1 year independently predicted poorer survival. Thus, eGFR
      may be a simple and economical biomarker in PAH.

PMID- 29174534
TI  - Subject-specific toe-in or toe-out gait modifications reduce the larger knee
      adduction moment peak more than a non-personalized approach.
AB  - The knee adduction moment (KAM) is a surrogate measure for medial compartment
      knee loading and is related to the progression of knee osteoarthritis. Toe-in and
      toe-out gait modifications typically reduce the first and second KAM peaks,
      respectively. We investigated whether assigning a subject-specific foot
      progression angle (FPA) modification reduces the peak KAM by more than assigning
      the same modification to everyone. To explore the effects of motor learning on
      muscle coordination and kinetics, we also evaluated the peak knee flexion moment
      and quadriceps-hamstring co-contraction during normal walking, when subjects
      first learned their subject-specific FPA, and following 20 min of training. Using
      vibrotactile feedback, we trained 20 healthy adults to toe-in and toe-out by 5
      degrees  and 10 degrees  relative to their natural FPA, then identified the
      subject-specific FPA as the angle where each subject maximally reduced their
      larger KAM peak. When walking at their subject-specific FPA, 18 subjects
      significantly reduced their larger KAM peak; 8 by toeing-in and 10 by toeing-out.
      On average, subjects reduced their larger KAM peak by 18.6 +/- 16.2% when walking
      at their subject-specific FPA, which was more than the reductions achieved when
      all subjects toed-in by 10 degrees  (10.0 +/- 17.1%, p = .013) or toed-out by 10
      degrees  (11.0 +/- 18.3%, p = .002). Quadriceps-hamstring co-contraction and the
      peak knee flexion moment increased when subjects first learned their subject
      specific FPA, but only co-contraction returned to baseline levels following
      training. These findings demonstrate that subject-specific gait modifications
      reduce the peak KAM more than uniformly assigned modifications and have the
      potential to slow the progression of medial compartment knee osteoarthritis.

PMID- 29174535
TI  - Prediction of inter-individual variability on the pharmacokinetics of CYP2C8
      substrates in human.
AB  - Inter-individual variability in pharmacokinetics can lead to unexpected side
      effects and treatment failure, and is therefore an important factor in drug
      development. CYP2C8 is a major drug-metabolizing enzyme known to be involved in
      the metabolism of over 100 drugs. In this study, we predicted the inter
      individual variability in AUC/Dose of CYP2C8 substrates in healthy volunteers
      using the Monte Carlo simulation. Inter-individual variability in the hepatic
      intrinsic clearance of CYP2C8 substrates (CLint,h,2C8) was estimated from the
      inter-individual variability in pharmacokinetics of pioglitazone, which is a
      major CYP2C8 substrate. The coefficient of variation (CV) of CLint,h,2C8 was
      estimated to be 40%. Using this value, the CVs of AUC/Dose of other major CYP2C8
      substrates, rosiglitazone and amodiaquine, were predicted to validate the
      estimated CV of CLint,h,2C8. As a result, the reported CVs of both substrates
      were within the 2.5-97.5 percentile range of the predicted CVs. Furthermore, the
      CVs of AUC/Dose of the CYP2C8 substrates loperamide and chloroquine, which are
      affected by renal clearance, were also successfully predicted. Combining this
      value with previously reported CVs of other CYPs, we were able to successfully
      predict the inter-individual variability in pharmacokinetics of various drugs in
      clinical.

PMID- 29174536
TI  - Monophosphorylation by deoxycytidine kinase affects apparent cellular uptake of
      decitabine in HCT116 colon cancer cells.
AB  - Decitabine (DAC), a nucleoside-related DNA methylation inhibitor, is taken up
      into cancer cells via equilibrative nucleoside transporter 1 (ENT1), and is then
      monophosphorylated by deoxycytidine kinase (dCK). In the present study, we
      examined the contribution of dCK to the uptake of DAC in HCT116 colon cancer
      cells. Irinotecan and etoposide inhibited the uptake of [3H]-uridine and [3H]-DAC
      at 10 s and 5 min, while cytarabine and gemcitabine only inhibited that of [3H]
      DAC at 5 min. Irinotecan and etoposide inhibited [3H]-DAC uptake in negative
      control small interfering RNA (siRNA)- or dCK siRNA-transfected cells at 10 s,
      whereas cytarabine and gemcitabine did not. Cytarabine and gemcitabine inhibited
      DAC monophosphate generation by the cytosolic proteins of HCT116 cells and
      recombinant human dCK protein, assessed using polyethylenimine cellulose thin
      layered chromatography. Simulations using simple kinetic models showed that
      apparent DAC uptake in dCK and ENT1 siRNA-treated cells was attributed to its
      conversion to monophosphates or a decrease in the cellular flux, respectively,
      and that the apparent uptake of DAC in dCK-knockdown and ENT1-knockdown cells was
      similar at longer times, but differed at a very short time. These results suggest
      that the apparent uptake of DAC is affected by ENT1 and dCK in HCT116 cells.

PMID- 29174537
TI  - Flow cytometry-based method for rapid and high-throughput screening of hybridoma
      cells secreting monoclonal antibody.
AB  - Monoclonal antibodies (mAbs) are a valuable biomaterial for basic life sciences
      and industrial purposes. The production of the mAb is time and effort intensive.
      In this report, we established a time- and labor-saving method for the mAb
      production. Because membrane-type immunoglobulin on a hybridoma cell surface and
      its secreted form, called as antibody, share the same binding property to the
      antigen, the fluorescence-labeled antigen bound to membrane-type immunoglobulin
      can be used as a screening marker. In the method, a hybridoma labeled by a
      fluorescent antigen was selected and sorted singly into 96-well plate using flow
      cytometer. Model experiments indicated that the method is highly efficient to
      obtain good mAbs suitable for Western blotting and immunofluorescence. Notably,
      most mAbs established by this method belonged to the IgG isotype, which is
      preferred over the IgM counterpart. Using a high-throughput flow cytometer, the
      method avoids tedious repeated screening and cloning processes. Because the
      method uses conventional myeloma for cell fusion and all reagents required in
      this method are commercially available, all research laboratories can apply the
      method to obtain mAbs efficiently.

PMID- 29174539
TI  - Innovation in the Delivery of Perinatal Health Care.

PMID- 29174538
TI  - Attendance at Mental Health Appointments by Women Who Were Referred During
      Pregnancy or the Postpartum Period.
AB  - OBJECTIVE: To describe characteristics of women referred to mental health care
      during pregnancy or the year after giving birth and to identify characteristics
      associated with attendance at mental health intake visits. DESIGN: Retrospective
      record review of referral documentation. SETTING: Women's health practices and
      perinatal mental health clinics in urban areas. PARTICIPANTS: The sample included
      647 women during pregnancy or the year after giving birth who were referred for
      mental health treatment. METHODS: We reviewed the referral data sent from women's
      health care providers to perinatal mental health clinics to determine if mental
      health visits occurred. RESULTS: Fifty percent of the 647 women who accepted
      perinatal mental health referrals had intake appointments. Women were more likely
      to participate in an intake appointment if in-home services were offered (p <
      .01). Those with lower income were also more likely to participate (p < 0.05).
      Those with histories of perinatal loss and those who self-referred tended to be
      more likely to participate, although these relationships were statistically
      nonsignificant. CONCLUSION: Even among women who accepted referrals to mental
      health services, only half attended intake appointments. For this group of
      pregnant women and those in the first year after birth, in-home mental health
      visits were most likely to result in care engagement, which has important
      implications for service delivery.

PMID- 29174540
TI  - Small-Molecule Kinase Downregulators.
AB  - New opportunities to advance small-molecule kinase ligands that downregulate
      their cognate target binding proteins are discussed. Rationally designed
      heterobifunctional kinase degraders are compared with ATP site ligands that were
      serendipitously found to cause kinase downregulation. These approaches could be
      particularly useful in the treatment of cancers since many kinases are known to
      remodel pro-oncogenic protein-protein interactions, which could be destroyed by
      small-molecule-mediated kinase depletion.

PMID- 29174541
TI  - Engineered Multivalent Sensors to Detect Coexisting Histone Modifications in
      Living Stem Cells.
AB  - The regulation of fundamental processes such as gene expression or cell
      differentiation involves chromatin states, demarcated by combinatorial histone
      post-translational modification (PTM) patterns. The subnuclear organization and
      dynamics of chromatin states is not well understood, as tools for their detection
      and modulation in live cells are lacking. Here, we report the development of
      genetically encoded chromatin-sensing multivalent probes, cMAPs, selective for
      bivalent chromatin, a PTM pattern associated with pluripotency in embryonic stem
      cells (ESCs). cMAPs were engineered from a set of PTM-binding (reader) proteins
      and optimized using synthetic nucleosomes carrying defined PTMs. Applied in live
      ESCs, cMAPs formed discrete subnuclear foci, revealing the organization of
      bivalent chromatin into local clusters. Moreover, cMAPs enabled direct monitoring
      of the loss of bivalency upon treatment with small-molecule epigenetic
      modulators. cMAPs thus provide a versatile platform to monitor chromatin state
      dynamics in live cells.

PMID- 29174543
TI  - New Models to Study Hepatitis E Virus Replication and Particular Characteristics
      of Infection: The Needle Hides in the Hay Stack.

PMID- 29174542
TI  - Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the
      Effect of Cellular ATP on Target Engagement.
AB  - For kinase inhibitors, intracellular target selectivity is fundamental to
      pharmacological mechanism. Although a number of acellular techniques have been
      developed to measure kinase binding or enzymatic inhibition, such approaches can
      fail to accurately predict engagement in cells. Here we report the application of
      an energy transfer technique that enabled the first broad-spectrum, equilibrium
      based approach to quantitatively profile target occupancy and compound affinity
      in live cells. Using this method, we performed a selectivity profiling for
      clinically relevant kinase inhibitors against 178 full-length kinases, and a
      mechanistic interrogation of the potency offsets observed between cellular and
      biochemical analysis. For the multikinase inhibitor crizotinib, our approach
      accurately predicted cellular potency and revealed improved target selectivity
      compared with biochemical measurements. Due to cellular ATP, a number of putative
      crizotinib targets are unexpectedly disengaged in live cells at a clinically
      relevant drug dose.

PMID- 29174544
TI  - Copper Directly Affects Intestinal Lipid Turnover.

PMID- 29174547
TI  - Living Like an Academic Athlete: How to Improve Clinical and Academic
      Productivity as a Gastroenterologist.

PMID- 29174546
TI  - Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients
      Coinfected With HBV.
AB  - BACKGROUND & AIMS: There have been reports of reactivation of hepatitis B virus
      (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct
      acting antiviral agents. We performed a prospective study of risks and outcomes
      of HCV infection treatment with ledipasvir and sofosbuvir in patients with HBV
      infection. METHODS: We performed a phase 3b, multicenter, open-label study in
      Taiwan of 111 patients with HCV infection (61% HCV genotype 1, 39% HCV genotype 2
      infection; 62% women, 16% with compensated cirrhosis) along with HBV infection.
      All but 1 were positive for the hepatitis B surface antigen (HBsAg); 1 patient
      who was HBsAg-positive at screening was found to be HBsAg-negative at baseline.
      Overall, 33% of participants had received prior treatment for HCV and 5% had
      previously been treated for HBV; no patient was on HBV therapy at the start of
      the study. All patients received a fixed-dose combination of 90 mg of the HCV
      NS5A inhibitor ledipasvir with 400 mg of the NS5B nucleotide analogue inhibitor
      sofosbuvir, once daily for 12 weeks. The primary endpoint was sustained virologic
      response 12 weeks after the end of therapy. RESULTS: All 111 patients (100%)
      achieved a sustained virologic response. Of the 37 patients with baseline HBV DNA
      below 20 IU/mL, 31 (84%) had at least 1 episode of quantifiable HBV DNA through
      posttreatment week 12. Of the 74 patients with baseline HBV DNA levels of 20
      IU/mL or more, 39 (53%) had increases of HBV DNA greater than 1 log10 IU/mL
      through posttreatment week 12. Overall, 5 patients had increased levels of HBV
      DNA concomitant with a level of alanine aminotransferase >2 times the upper limit
      of normal through posttreatment week 12. Of these, 3 patients started HBV
      treatment. In addition, 1 patient with HBV reactivation since week 8 and
      concomitant alanine aminotransferase elevation >2 times upper limit of normal at
      posttreatment week 48 started treatment at posttreatment week 53. This patient
      had clinical signs and symptoms associated with HBV reactivation. The most common
      adverse events were headache, upper respiratory infection, and fatigue.
      CONCLUSIONS: In a prospective study, the combination of ledipasvir and sofosbuvir
      for 12 weeks produced a sustained virologic response in 100% of patients with HCV
      infection who were coinfected with HBV. Most patients had an increase in level of
      HBV DNA not associated with signs or symptoms. ClinicalTrials.gov no:
      NCT02613871.

PMID- 29174548
TI  - The Role of Transforming Growth Factor-beta in Human Hepatocarcinogenesis:
      Mechanistic and Therapeutic Implications From an Integrative Multiomics Approach.

PMID- 29174549
TI  - Identification and characterization of potential druggable targets among
      hypothetical proteins of extensively drug resistant Mycobacterium tuberculosis
      (XDR KZN 605) through subtractive genomics approach.
AB  - Among the resistant isolates of tuberculosis (TB), the multidrug resistance
      tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) are
      the areas of growing concern for which the front-line antibiotics are no more
      effective. As a result, the search of new therapeutic targets against TB is an
      imperative need of time. On the other hand, the target identification is an a
      priori step in drug discovery based research. Furthermore, the availability of
      the complete proteomic data of extensively drug resistant Mycobacterium
      tuberculosis (XDR-MTB) made it possible to carry out in silico analysis for the
      discovery of new drug targets. In the current study, we aimed to prioritize the
      potential drug targets among the hypothetical proteins of XDR-TB via subtractive
      genomics approach. In the subtractive genomics, we stepwise reduced the complete
      proteome of XDR-MTB to only two hypothetical proteins and evidently proposed them
      as new therapeutic targets. The 3D structure of one of the two target proteins
      was predicted via homology modeling and later on, validated by various analysis
      tools. Our study suggested that the domains identified and the motif hits found
      in the sequences of the shortlisted drug targets are crucial for the survival of
      the XDR-MTB. To the best of our knowledge, the current study is the first attempt
      in which the complete proteomic data of XDR-MTB was subjected to the
      computational subtractive genomics approach and therefore, would provide an
      opportunity to identify the unique therapeutic targets against deadly XDR-MTB.

PMID- 29174550
TI  - Three-dimensional changes of scleral show after surgical treatment of endocrine
      orbitopathy.
AB  - PURPOSE: Surgery in endocrine orbitopathy should address exophthalmos and adjunct
      stigmata such as increased lid aperture and scleral show. Secondary to
      decompression, rehabilitative surgical treatment such as blepharoplasty is
      routinely used to achieve this goal. Until now, however, there has been no
      investigation to measure the effect of decompression surgery on scleral show and
      lid aperture 3-dimensionally. MATERIALS AND METHODS: Ocular surface area (OSA)
      and lid aperture of 34 patients (67 orbits) were measured pre and post
      decompression surgery in a retrospective investigation using 3-dimensional (3D)
      stereophotogrammetry. The mean follow-up after decompression was 6 +/- 4 months.
      RESULTS: Mean OSA ranged between 3.1 +/- 1.5 cm2 (pre orbital decompression) and
      2.5 +/- 0.6 cm2 (post orbital decompression). Orbital decompression caused a
      statistically significant reduction of the surface area of about 19.4% (p <
      0.001). Lid apertures showed average values between 12.7 +/- 3.3 mm (pre orbital
      decompression) and 11.3 +/- 2.2 mm (post orbital decompression). Thus orbital
      decompression led to a statistically significant reduction of the palpebral
      fissure of about 11% (p < 0.001). OSA correlated with lid aperture pre and post
      surgery (p < 0.001). The extent of OSA reduction showed no correlation with the
      amount of exophthalmos reduction. CONCLUSION: Our results show that surgical
      decompression, besides correcting exophthalmos, leads to a significant reduction
      of scleral show and lid aperture. However, it is not possible to estimate its
      effect on an individual basis.

PMID- 29174551
TI  - Surgical management of severe osteoradionecrosis of the mandibular bone by using
      double free flap reconstruction.
AB  - PURPOSE: Osteoradionecrosis (ORN) of the jaws represents one of the most severe
      complications after primary or adjuvant radiation therapy (RT) of large head and
      neck tumors. In advanced ORN cases, surgical management is generally considered
      the therapy of choice. However, in several severe ORN patients with extensive
      bone and soft tissue defects, functional and aesthetic reconstruction represents
      a huge challenge for any surgeon, with an increased risk of post-operative wound
      healing disorders. Our aim here was to perform a double free flap technique as a
      therapeutic option in this difficult patient collective and to evaluate the post
      operative outcome. MATERIALS AND METHODS: 15 patients with advanced and severe
      ORN undergoing mandibular and soft tissue reconstruction with a double free flap
      were retrospectively reviewed. In one single operation involving a three-team
      approach, an obligatory free fibular flap (FFF) was freely combined with another
      free flap according to the desired features: anterolateral thigh (ALT) or vastus
      lateralis flap (VLF), radial forearm flap (RFF) and latissimus dorsi flap (LDF).
      RESULTS: We found sufficient wound healing in the head and neck region in all
      patients with no need for any additional surgical intervention. The overall flap
      success rate was 93.3%, although three revisions of anastomosis were necessary.
      Furthermore, prolonged stay on the intensive care unit (ICU) and extended
      hospitalisation were avoided. CONCLUSION: The double free flap technique with an
      obligatory FFF provides a suitable surgical solution for the treatment of
      patients with severe ORN of the mandibular bone for which other conservative or
      surgical therapy strategies have reached their limits.

PMID- 29174552
TI  - Simultaneous reconstruction of columella and philtrum using prolabial flap
      combined with Abbe flap in secondary bilateral cleft lip and nasal deformity.
AB  - Open rhinoplasty and Abbe flap techniques are traditionally useful tools for the
      reconstruction of secondary bilateral cleft lip nasal (BCLN) deformity. We aimed
      to investigate the long-term outcomes of simultaneous columella and philtrum
      reconstruction using prolabial flap combined with Abbe flap in secondary BCLN
      deformity. From January 2009 to July 2014, 26 patients (17 males and 9 females;
      mean age 21 years) with secondary BCLN deformity were recruited. All patients had
      severe short columella and philtrum deficiency. The whole superiorly based
      prolabial flap was harvested and trimmed for columella reconstruction. An Abbe
      flap from the central lower lip was elevated to reconstruct the esthetic philtral
      unit. No flap necrosis occurred postoperatively. The average follow-up was 2.7
      years. The columella length was 4.7 +/- 1.3 mm preoperatively and 10.4 +/- 2.1 mm
      postoperatively. The philtrum length increased to 14.4 +/- 2.6 mm postoperatively
      from a preoperative 8.9 +/- 2.4 mm. Regarding the overall impression of the
      reconstruction, 22 patients ranked it as very good or good. In secondary BCLN
      deformity, the prolabial flap combined with Abbe flap technique is an effective
      alternative for the treatment of severe short columella complicated with severe
      philtrum deficiency.

PMID- 29174553
TI  - Primary aesthetic correction of nasal anomaly with costal graft in treating
      orbital hypertelorism.
AB  - : Orbital hypertelorism is a common congenital craniofacial anomaly in Asians. As
      Tessier pointed out, the correction of hypertelorism is effectively the
      correction of the nasal deformity, which is characterized by a broad, flat nose
      accompanying an increased interorbital distance and a lack of nasal projection.
      OBJECTIVES: To measure the changes in the orbital and nasal parameters after
      Tessier box osteotomy and primary aesthetic rhinoplasty, performed concurrently
      with otogenous costochondral graft. METHODS: From 2009 to 2013, 49 hypertelorism
      patients were treated in our craniofacial unit. Correction involved a classic
      Tessier box osteotomy combined with aesthetic augmentation and reconstruction of
      the nasal dorsum using a costochondral graft. All patients underwent photographic
      and tomographic documentation both before and 12 months after surgery. Patients
      underwent morphometric analysis to document the change in interorbital distance,
      IOD, hypertelorism index, and aesthetic nasal parameters, including the nasal
      dorsum and alar width, the nasal dorsal height, and the index of nasal apex
      protrusion versus nasal length. RESULTS: All patients were satisfied with the
      outcome of the combined orbital and nasal repair. Morphometric analysis indicated
      that the IOD, hypertelorism index, and aesthetic nasal parameters all improved
      following surgery. The resorption rate of the costochondral graft was 16-19%, and
      graft warpage was nearly absent. Although complications included infection,
      cerebrospinal fluid leak, and hyposomia, no severe or life-threatening
      complications occurred. CONCLUSION: Tessier box osteotomy with primary aesthetic
      rhinoplasty using costochondral grafts has shown to be efficacious in the
      treatment of patients with hypertelorism.

PMID- 29174554
TI  - Novel computer vision analysis of nasal shape in children with unilateral cleft
      lip.
AB  - BACKGROUND: Optimization of treatment of the unilateral cleft lip nasal deformity
      (uCLND) is hampered by lack of objective means to assess initial severity and
      changes produced by treatment and growth. The purpose of this study was to
      develop automated 3D image analysis specific to the uCLND; assess the correlation
      of these measures to esthetic appraisal; measure changes that occur with
      treatment and differences amongst cleft types. METHODS: Dorsum Deviation, Tip
      Alar Volume Ratio, Alar-Cheek Definition, and Columellar Angle were assessed
      using computer-vision techniques. Subjects included infants before and after
      primary cleft lip repair (N = 50) and children aged 8-10 years with previous
      cleft lip (N = 50). Two expert surgeons ranked subjects according to esthetic
      nose appearance. RESULTS: Computer-based measurements strongly correlated with
      rankings of infants pre-repair (r = 0.8, 0.75, 0.41 and 0.54 for Dorsum
      Deviation, Tip-Alar Volume Ratio, Alar-Cheek Definition, and Columellar Angle, p
      < 0.01) while all measurements except Alar-Cheek Definition correlated moderately
      with rankings of older children post-repair (r ~ 0.35, p < 0.01). Measurements
      were worse with greater severity of cleft type but improved following initial
      repair. Abnormal Dorsum Deviation and Columellar Angle persisted after surgery
      and were more severe with greater cleft type. CONCLUSIONS: Four fully-automated
      measures were developed that are clinically relevant, agree with expert
      evaluations and can be followed through initial surgery and in older children.
      Computer vision analysis techniques can quantify the nasal deformity at different
      stages, offering efficient and standardized tools for large studies and data
      driven conclusions.

PMID- 29174556
TI  - Risk of borderline ovarian tumors among women with benign ovarian tumors: A
      cohort study.
AB  - OBJECTIVE: A growing number of studies suggest that some ovarian cancers can
      arise from benign and borderline ovarian tumors. However, studies on the
      association between benign and borderline ovarian tumors are lacking. We studied
      the overall- and histotype-specific risk of borderline ovarian tumors among women
      with a benign ovarian tumor. METHODS: This nationwide cohort study included all
      Danish women diagnosed with a benign ovarian tumor (n=139,466) during 1978-2012.
      The cohort was linked to the Danish Pathology Data Bank and standardized
      incidence ratios (SIR) with 95% confidence intervals (CI) were calculated.
      RESULTS: Women with benign ovarian tumors had increased risks for subsequent
      borderline ovarian tumors (SIR 1.62, 95% CI 1.43-1.82), and this applied to both
      serous (SIR 1.69, 95% CI 1.39-2.03) and mucinous (SIR 1.75, 95% CI 1.45-2.10)
      histotypes of borderline ovarian tumors. The risk for borderline ovarian tumors
      was primarily increased for women diagnosed with a benign ovarian tumor before
      40years of age. The risk remained increased up to 9years after a benign ovarian
      tumor diagnosis. Finally, the associations did not change markedly when analyzed
      for the different histotypes of benign (solid and cystic tumors) and borderline
      (serous and mucinous tumors) ovarian tumors. CONCLUSIONS: Women with benign
      ovarian tumors have a long-term increased risk for borderline ovarian tumors.
      However, as all associations in this study were only adjusted for age and
      calendar period of diagnosis, more studies that are able to adjust for additional
      potential confounding variables are required to further understand these
      associations.

PMID- 29174557
TI  - Not all is noticed: Kinematic cues of emotion-specific gait.
AB  - Perceiving emotions from gait can serve numerous socio-environmental functions
      (e.g. perceiving threat, sexual courting behaviours). Participant perceivers were
      asked to report their strategies for identifying happiness, sadness, anger and
      fear in point-light walkers. Perceivers claimed they identified happiness by a
      bouncing gait with increased arm movement, sadness by a slow slouching gait,
      anger by a fast stomping gait and fear by both fast and slow gaits. The emotion
      specific point-light walker stimuli were kinematically analysed to verify the
      presence of the gait cues perceivers reported using to identify each emotion.
      Happy and angry walkers both displayed long strides with increased arm movement
      though angry strides had a faster cadence. Fearful walkers walked with fast short
      strides reminiscent of a scurrying gait. Sad walkers walked with slow short
      strides consequently creating the slowest walking pace. However, fearful and sad
      walkers showed less arm movement in their gait in different ways. Sad walkers
      moved their entire arms whilst fearful walkers primarily moved their lower arms
      throughout their gait.

PMID- 29174555
TI  - Predictive modeling for determination of microscopic residual disease at primary
      cytoreduction: An NRG Oncology/Gynecologic Oncology Group 182 Study.
AB  - OBJECTIVE: Microscopic residual disease following complete cytoreduction (R0) is
      associated with a significant survival benefit for patients with advanced
      epithelial ovarian cancer (EOC). Our objective was to develop a prediction model
      for R0 to support surgeons in their clinical care decisions. METHODS:
      Demographic, pathologic, surgical, and CA125 data were collected from GOG 182
      records. Patients enrolled prior to September 1, 2003 were used for the training
      model while those enrolled after constituted the validation data set. Univariate
      analysis was performed to identify significant predictors of R0 and these
      variables were subsequently analyzed using multivariable regression. The
      regression model was reduced using backward selection and predictive accuracy was
      quantified using area under the receiver operating characteristic area under the
      curve (AUC) in both the training and the validation data sets. RESULTS: Of the
      3882 patients enrolled in GOG 182, 1480 had complete clinical data available for
      the analysis. The training data set consisted of 1007 patients (234 with R0)
      while the validation set was comprised of 473 patients (122 with R0). The reduced
      multivariable regression model demonstrated several variables predictive of R0 at
      cytoreduction: Disease Score (DS) (p<0.001), stage (p=0.009), CA125 (p<0.001),
      ascites (p<0.001), and stage-age interaction (p=0.01). Applying the prediction
      model to the validation data resulted in an AUC of 0.73 (0.67 to 0.78, 95% CI).
      Inclusion of DS enhanced the model performance to an AUC of 0.83 (0.79 to 0.88,
      95% CI). CONCLUSIONS: We developed and validated a prediction model for R0 that
      offers improved performance over previously reported models for prediction of
      residual disease. The performance of the prediction model suggests additional
      factors (i.e. imaging, molecular profiling, etc.) should be explored in the
      future for a more clinically actionable tool.

PMID- 29174558
TI  - Anesthesia and sleep apnea.
AB  - Due to its low rate of diagnosis, in the general population over half of those
      experiencing obstructive sleep apnea (OSA) are unaware that they have the
      condition. However, any acute medical event may exacerbate OSA and could have
      serious health consequences. In this context the management of the perioperative
      period, from anesthesia through the surgery itself and into the postoperative
      period, is more problematic for patients with sleep disordered breathing than for
      others. There is prolific literature in this area although large randomized
      trials are few due to the high sample size needed and possible ethical
      difficulties of withholding OSA treatment in the perioperative period. In 2014
      the American Society of Anesthesiologists published an updated set of
      recommendations to guide OSA management during the perioperative period. In this
      present review we provide an overview of the different issues that practitioners
      face with regard to OSA, from the initial consultation with the anesthesiologist
      to the extended post-operative period. There is considerable evidence that OSA
      patients are at high risk of perioperative complications, though the inherent
      risks from OSA per se and its comorbidities remain difficult to discern.
      Nevertheless, appropriate screening and management allow clinicians to minimize
      OSA associated risk.

PMID- 29174559
TI  - Assessment of the severity of native mitral valve regurgitation.
AB  - Mitral regurgitation (MR) is a major cause of cardiovascular morbidity and
      mortality. MR is classified as primary (organic) if it is due to an intrinsic
      valve abnormality, or secondary (functional) if the etiology is because of
      remodeling of left ventricular geometry and/or valve annulus. Transthoracic
      echocardiography (TTE) is the initial modality for MR evaluation. Parameters used
      for the assessment of MR include valve structure, cardiac remodeling, and color
      and spectral Doppler. Quantitative measurements include effective regurgitant
      orifice area, regurgitant volume, and regurgitant fraction. Knowledge of
      advantages and limitations of echo-Doppler parameters is essential for accurate
      results. An integrative approach is recommended in overall grading of MR as mild,
      moderate, or severe since singular parameters may be affected by several factors.
      When the mechanism and/or grade of MR is unclear from the TTE or is discrepant
      with the clinical scenario, further evaluation with transesophageal
      echocardiography or cardiac magnetic resonance imaging is recommended, the latter
      emerging as a powerful MR quantitation tool.

PMID- 29174561
TI  - Successful Ageing in Nonagenarians: Bio-psychosocial Factors Determining
      Successful Ageing in Long-Lived Older Adults.

PMID- 29174560
TI  - Resident Vignettes for Assessing Care Quality in Nursing Homes.
AB  - OBJECTIVES: Validated process measures that correlate with patient outcomes are
      needed for research and quality improvement. DESIGN: Cross-sectional analysis
      within a cluster-randomized fall prevention study. SETTING: Nursing homes in
      North Carolina (n = 16). PARTICIPANTS: Nursing home staff (n = 541) and residents
      with 1 or more falls in 6 months (n = 597). MEASUREMENTS: Fall-prevention process
      measures in 4 categories derived from Assessing Care of Vulnerable Elders quality
      indicators were measured in 2 ways: (1) chart abstraction; and (2) staff
      responses to clinical vignettes of hypothetical residents at risk for falls.
      Recurrent fall rates (falls/resident/year) were measured. The proportion of the
      total variation in falls rates explained by the scores for each method (chart
      abstraction or vignette) was calculated using multilevel adjusted models.
      RESULTS: Chart and vignette measures of comorbidity management were moderately
      correlated (Pearson correlation coefficient 0.43), whereas other process measure
      categories had low or negative correlation between the 2 methods (psychoactive
      medication reduction 0.13, environmental modification -0.42, and
      exercise/rehabilitation -0.08). Measures of environmental modification and
      comorbidity management explained a moderate amount of the total variation in
      recurrent fall fates, vignettes (7%-10% variation explained) were superior to
      chart abstraction (2%-6% variation explained). Vignette responses from unlicensed
      staff (nurse aides and rehabilitation aides) explained more variance than
      registered nurses, licensed practical nurses, or other licensed staff in these
      categories. Process measures for psychoactive medication reduction and
      exercise/rehabilitation did not explain any of the variation in fall outcomes.
      Overall, vignette process measures explained 3.9% and chart abstraction measures
      explained 0% of the variation in fall outcomes. CONCLUSIONS: Clinical vignettes
      completed by nursing home staff had greater association with resident recurrent
      fall rates than traditional chart abstraction process measures.

PMID- 29174562
TI  - An Even Distribution of Protein Intake Daily Promotes Protein Adequacy but Does
      Not Influence Nutritional Status in Institutionalized Elderly.
AB  - OBJECTIVE: Although it has been established that sufficient protein is required
      to maintain good nutritional status and support healthy aging, it is not clear if
      the pattern of protein consumption may also influence nutritional status,
      especially in institutionalized elderly who are at risk of malnutrition.
      Therefore, we aim to determine the association between protein intake
      distribution and nutritional status in institutionalized elderly people. DESIGN:
      Cross-sectional study among 481 institutionalized older adults. METHODS: Dietary
      data from 481 ambulant elderly people (68.8% female, mean age 87.5 +/- 6.3 years)
      residing in 52 aged-care facilities in Victoria, Australia, were assessed over 2
      days using plate waste analysis. Nutritional status was determined using the Mini
      Nutritional Assessment tool and serum (n = 208) analyzed for albumin, hemoglobin,
      and IGF-1. Protein intake distribution was classified as: spread (even
      distribution across 3 meals, n = 65), pulse (most protein consumed in one meal, n
      = 72) or intermediate (n = 344). Regression analysis was used to investigate
      associations. RESULTS: Mean protein intakes were higher in the spread (60.5 +/-
      2.0 g/d) than intermediate group (56.0 +/- 0.8 g/d, P = .037), and tended to be
      higher than those in the pulse group (55.9 +/- 1.9 g/d, P = .097). Residents with
      an even distribution of protein intake achieved a higher level of the recommended
      daily intake for protein (96.2 +/- 30.0%) than the intermediate (86.3 +/- 26.2%,
      P = .008) and pulse (87.4 +/- 30.5%, P = .06) groups, and also achieved a greater
      level of their estimated energy requirements (intermediate; P = .039, pulse; P =
      .001). Nutritional status (Mini-Nutritional Assessment score) did not differ
      between groups (pulse; 20.5 +/- 4.5, intermediate; 21.0 +/- 2.5, spread; 20.5 +/-
      3.5), nor did any other indices of nutritional status. CONCLUSIONS: Meeting
      protein requirements is required before protein distribution may influence
      nutritional status in institutionalized elderly. Achieving adequate protein and
      energy intakes is more likely when protein is distributed evenly throughout the
      day. Provision of high protein foods especially at breakfast, and in the evening,
      may support protein adequacy and healthy aging, especially for institutionalized
      elderly.

PMID- 29174563
TI  - Invasive fungi-derived defensins kill drug-resistant bacterial pathogens.
AB  - Fungi-derived defensins are a class of antimicrobial peptides with therapeutic
      potential due to their high antibacterial efficacy and low toxicity. Based on the
      genomic strategy, we have identified 68 fungal defensin-like peptides (fDLPs) in
      five new genera, including Trichosporon, Apophysomyces, Lichtheimia, Beauveria
      and Scedosporium and characterized a new synthetic defensin (scedosporisin) from
      an invasive fungus. It was active against Gram-positive bacteria but not active
      against negative bacteria. Importantly, it killed several clinical resistant
      isolates such as methicillin-resistant Staphylococcus aureus and vancomycin
      resistant Enterococci at low molecular concentrations. Scedosporisin showed low
      hemolysis and cytotoxicity and high serum stability. The killing kinetics of
      scedosporisin-2 against a clinical isolate of MRSA showed that it killed the
      bacteria more rapidly than that of vancomycin. Homology modeling analysis show
      that scedosporisin adopted a typical cysteine stabilized alpha-helical and beta
      sheet fold with a local hydrophobic patch. Scedosporisin significantly improved
      the survival rate of mice in the peritonitis model. This work has greatly
      expanded the library of fDLPs, and successfully selected leading molecules for
      antimicrobial drug reserves.

PMID- 29174564
TI  - Crispr-Cas9 engineered osteogenesis imperfecta type V leads to severe skeletal
      deformities and perinatal lethality in mice.
AB  - Osteogenesis imperfecta (OI) type V is caused by an autosomal dominant mutation
      in the IFITM5 gene, also known as BRIL. The c.-14C>T mutation in the 5'UTR of
      BRIL creates a novel translational start site adding 5 residues (MALEP) in frame
      with the natural coding of BRIL. A neomorphic function has been proposed for the
      MALEP-BRIL but the mechanisms at play are still unknown. In order to further
      understand the effects of MALEP-BRIL in vivo, we generated a knockin (KI) mouse
      model having the exact genetic -14C>T replica of patients with OI type V. Live KI
      descendants were never obtained from 2 male mosaic founders. Skeletal staining
      with alizarin red/alcian blue and MUCT imaging of KI embryos revealed striking
      skeletal anomalies such as hypomineralized skull, short and bent long bones, and
      frail and wavy ribs. Histology and histochemical labeling revealed that midshaft
      of long bones was filled with hypertrophic chondrocytes, lacked a defined primary
      ossification center with the absence of defined cortices. Gene expression
      monitoring at E15.5 and E17.5 showed no change in Osx but decreased Bril itself
      as well as other differentiated osteoblast markers (Ibsp, Bglap, Sost). However,
      upregulation of Ptgs2 and Nr4a3 suggested that a pro-inflammatory reaction was
      activated. Primary osteoblasts from KI calvaria showed delayed differentiation
      and mineralization, with decreased abundance of BRIL. However, the upregulation
      AdipoQ and Fabp4 in young cultures indicated a possible switch in fate towards
      adipogenesis. Altogether our data suggest that the low level expression of MALEP
      BRIL in Osx+ mesenchymal progenitors blunted their further differentiation into
      mature osteoblasts, which may have resulted in part from an inflammatory
      response.

PMID- 29174565
TI  - The use of patient-reported outcome tools in Gynecologic Oncology research,
      clinical practice, and value-based care.
AB  - Patient-reported outcomes (PRO) are defined as a report of a patient's symptoms,
      function and general well-being that comes directly from the patient, without
      interpretation of the response by a medical provider. As greater emphasis is
      placed on high-quality, patient-centered care, the importance of PROs has become
      widely accepted by policymakers, third party payers, medical societies, health
      care systems and clinical researchers. Despite increased recognition of the
      importance of PROs, they have not become a widely-implemented part of clinical
      care and their use in clinical research has been limited by methodological
      concerns. Health service researchers and providers are working to standardize and
      develop new methods to improve implementation of PROs in clinical and research
      settings. This article reviews the development of PRO measurement tools,
      implementation in the healthcare setting and relevance in clinical trials, with a
      focus on clinical care and research in gynecologic oncology.

PMID- 29174567
TI  - The unrecognized burden of cardiovascular risk factors in women newly diagnosed
      with endometrial cancer: A prospective case control study.
AB  - BACKGROUND: Cardiovascular disease is a major cause of death in endometrial
      cancer survivors. The aim of this study was to determine whether women newly
      diagnosed with endometrial cancer have a higher prevalence of cardiovascular risk
      factors than the general population. METHODS: The prevalence of adequately
      treated and unrecognized/inadequately treated cardiovascular risk factors and the
      corresponding 10-year cardiovascular risk by QRISK2 score was measured in 150
      consecutive women undergoing primary treatment for endometrioid endometrial
      cancer in the North West of England, and 746 age and ethnicity-matched control
      women from the Health Survey for England 2014. RESULTS: Women with endometrial
      cancer had higher proportions of obesity (BMI>=30 60.7% vs. 32.4%, p<0.0001) and
      a preponderance of unrecognized and inadequately treated cardiovascular risk
      factors. Compared with controls, endometrial cancer cases had a higher prevalence
      of incident hyperglycemia (57.2%vs.11.5%, p<0.0001), total: HDL cholesterol
      ratio>4.5 (26.7%vs.13.7%, p<0.0001), and were more likely to have three or more
      cardiovascular risk factors (22%vs.6%, p<0.0001). This equates to a higher 10
      year cardiovascular risk (median QRISK2 score 12.6% vs. 8.8%, p<0.0001).
      Optimization of risk factors would have a greater impact on absolute
      cardiovascular disease risk for cases than controls (QRISK2 score reduction 1.8%
      vs. 0.7%). CONCLUSIONS: Women undergoing primary treatment for endometrial cancer
      have a higher prevalence of cardiovascular risk factors than women without the
      disease. Early identification and treatment of these risk factors could improve
      outcomes for endometrial cancer survivors.

PMID- 29174566
TI  - The roles of pathology in targeted therapy of women with gynecologic cancers.
AB  - The role of the pathologist in the multidisciplinary management of women with
      gynecologic cancer has evolved substantially over the past decade. Pathologists'
      evaluation of parameters such as pathologic stage, histologic subtype, grade and
      microsatellite instability, and their identification of patients at risk for
      Lynch syndrome have become essential components of diagnosis, prognostic
      assessment and determination of optimal treatment of affected women. Despite the
      use of multimodality treatment and combination cytotoxic chemotherapy, the
      prognosis of women with advanced-stage gynecologic cancer is often poor.
      Therefore, expanding the arsenal of available systemic therapies with targeted
      therapeutic agents is appealing. Anti-angiogenic therapies, immunotherapy and
      poly ADP ribose polymerase (PARP) inhibitors are now routinely used for the
      treatment of advanced gynecologic cancer, and many more are under investigation.
      Pathologists remain important in the clinical management of patients with
      targeted therapy, by identifying potentially targetable tumors on the basis of
      their pathologic phenotype, by assessing biomarkers that are predictive of
      response to targeted therapy (e.g. microsatellite instability, PD1/PDL1
      expression), and by monitoring treatment response and resistance. Pathologists
      are also vital to research efforts exploring novel targeted therapies by
      identifying homogenous subsets of tumors for more reliable and meaningful
      analyses, and by confirming expression in tumor tissues of novel targets
      identified in genomic, epigenetic or other screening studies. In the era of
      precision gynecologic oncology, the roles of pathologists in the discovery,
      development and implementation of targeted therapeutic strategies remain as
      central as they are for traditional (surgery-chemotherapy-radiotherapy)
      management of women with gynecologic cancers.

PMID- 29174568
TI  - Small bowel adenocarcinoma: French intergroup clinical practice guidelines for
      diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED,
      SFRO).
AB  - BACKGROUND: This document is a summary of the French intergroup guidelines
      regarding the management of small bowel adenocarcinoma published in October 2016.
      METHOD: This collaborative work, co-directed by most French Medical Societies,
      summarizes clinical practice recommendations (guidelines) on the management of
      small bowel adenocarcinoma. Given the lack of specific data in the literature,
      all references are given by analogy with colon cancer. The classification used is
      the AJCC (American Joint Committee on Cancer) pTNM classification (7th edition
      2009). RESULTS: Small bowel adenocarcinoma has a poor prognosis; less than 30% of
      patients survive for 5 years after the (first) diagnosis (5-year survival of less
      than 30%). Due to the rarity of the disease and the retrospective data, most
      recommendations are based on expert agreement. The initial evaluation is based on
      chest-abdomen-pelvis CT scan, CEA assay, GI endoscopy and colonoscopy in order
      detect lesions associated with a predisposing disease. Surgical treatment is
      currently the only curative option for stage I and II. Adjuvant chemotherapy can
      be discussed for Stage III and Stage II with T4 (expert agreement). With regard
      to metastatic tumors, treatment with fluoropyrimidine combined with platinum
      salts should be considered (expert agreement). CONCLUSION: Few specific data
      exist in the literature on this type of tumor; most of the recommendations come
      from expert agreements or by analogy with colon cancer. Thus, each case must be
      discussed within a multidisciplinary team.

PMID- 29174569
TI  - A modified Poisson-Boltzmann equation applied to protein adsorption.
AB  - Ion-exchange chromatography has been widely used as a standard process in
      purification and analysis of protein, based on the electrostatic interaction
      between the protein and the stationary phase. Through the years, several
      approaches are used to improve the thermodynamic description of colloidal
      particle-surface interaction systems, however there are still a lot of gaps
      specifically when describing the behavior of protein adsorption. Here, we present
      an improved methodology for predicting the adsorption equilibrium constant by
      solving the modified Poisson-Boltzmann (PB) equation in bispherical coordinates.
      By including dispersion interactions between ions and protein, and between ions
      and surface, the modified PB equation used can describe the Hofmeister effects.
      We solve the modified Poisson-Boltzmann equation to calculate the protein-surface
      potential of mean force, treated as spherical colloid-plate system, as a function
      of process variables. From the potential of mean force, the Henry constants of
      adsorption, for different proteins and surfaces, are calculated as a function of
      pH, salt concentration, salt type, and temperature. The obtained Henry constants
      are compared with experimental data for several isotherms showing excellent
      agreement. We have also performed a sensitivity analysis to verify the behavior
      of different kind of salts and the Hofmeister effects.

PMID- 29174570
TI  - Synthesis of short-chain hydroxyaldehydes and their 2,4-dinitrophenylhydrazone
      derivatives, and separation of their isomers by high-performance liquid
      chromatography.
AB  - An easy to handle high-performance liquid chromatography (HPLC) method for the
      separation of structural isomers of short-chain aldehydes as their hydrazones is
      presented. Some aldehydes were not available as reference compounds, therefore,
      synthesis routes for these hydroxy-aldehydes and their dinitrophenylhydrazone
      derivatives are reported. The reported method has a detection limit of 2.4
      16.1MUg/L for the hydrazones and shows good linearity and reproducibility for
      various tested aldehydes.

PMID- 29174571
TI  - A chromatographic study on the exceptional chiral recognition of 2
      (benzylsulfinyl)benzamide by an immobilized-type chiral stationary phase based on
      cellulose tris(3,5-dichlorophenylcarbamate).
AB  - In previous studies, Okamoto et al. described the results of the exceptionally
      large chiral recognition of 2-(benzylsulfinyl)benzamide onto a coated-type chiral
      stationary phase based on cellulose tris(3,5-dichlorophenylcarbamate). As a
      continuation and deepening of those studies, here the sulfoxide and a small set
      of its structural analogues were analyzed on the commercially available Chiralpak
      IC-3 chiral stationary phase based upon the same polysaccharide derivative as the
      chiral selector but immobilized onto silica support. The chromatographic results
      obtained using different mobile phases consisting of pure methanol, ethanol and 2
      propanol or binary mixtures n-hexane-2-propanol, which are prohibited with the
      progenitor coated-type chromatographic support, permitted to identify the NH2 of
      the amide group as the key structural element of the (S)-enantiomer of 2
      (benzylsulfinyl)benzamide for obtaining a very high affinity for the IC-3 chiral
      stationary phase.

PMID- 29174572
TI  - Applications of 2, 2, 2 trifluoroethanol as a versatile co-solvent in
      supercritical fluid chromatography for purification of unstable boronate esters,
      enhancing throughput, reducing epimerization, and for additive free
      purifications.
AB  - Analysis and purification of boronic acid pinacol esters by RPLC is very
      challenging due to their degradation in aqueous and alcoholic solvents. These
      compounds are difficult to purify by SFC too as they are equally sensitive to
      traditional co-solvents like methanol, ethanol, and 2-propanol. 2,2,2
      trifluoroethanol (TFE), which has been reported for the purification of a few
      alcohol sensitive compounds, was evaluated as a co-solvent in this study for the
      purification of chiral and achiral boronate esters by SFC. Examples of twelve
      compounds were presented in this paper where degradation of boronic acid pinacol
      esters was successfully controlled by replacing methanol with TFE as the co
      solvent in SFC. A separate study showed that TFE can also control the
      epimerization of the enantiomers of 3 substituted 1,4 benzodiazepine analogues
      during the purification process. In addition to above benefits,
      2,2,2trifloroethanol showed improved selectivity and resolution for most of the
      compounds. With its stronger solvent strength compared to other alcohols, TFE
      could also be used to reduce the co-solvent percentage needed for elution and to
      shorten retention time of highly polar samples which did not elute even in 50% of
      other co-solvents in SFC. A case study of compound B demonstrated that TFE
      provided a reduced co-solvent percentage and a shorter cycle time with much
      improved resolution as compared to methanol, thus resulting in higher loading and
      throughput with reduction of total solvent consumption.

PMID- 29174573
TI  - [6th congress of the Association francaise des chirurgiens de la face. Honfleur
      22 to 24 June 2017].

PMID- 29174574
TI  - Enhanced neurogenesis in degenerated hippocampi following pretreatment with miR
      302/367 expressing lentiviral vector in mice.
AB  - Astrogliosis is the main landmark of neurodegenerative diseases. In vivo
      reprogramming of reactive astrocytes to functional neurons opened a new horizon
      in regenerative medicine. However there is little evidence that show possible
      application of in vivo reprogramming approaches for enhancement of neurogenesis.
      Cluster miR-302/367 showed high capability in cell reprogramming. Here we show
      that application of lentiviral particles expressing cluster miR-302/367 along
      with systemic valproate (VPA) enhanced the capability of mice brains for
      neurogenesis in CA3 area following kainic acid (KA) induced hippocampal
      neurodegeneration. Following pretreatment with miR-302/367 expressing viral
      particles and VPA, transduced cells showed neuroblast and mature neuron markers
      when neuronal loss was induced by KA. Comparing the neuron counts in CA3 region
      also showed that neurogenesis was increased in CA3 region in animals which were
      pretreated with miR-302/367 vector and VPA, only in injected side of the brain.
      Our data suggest that targeted application of miR-302/367 expressing vector may
      enhance the capacity of hippocampus and other brain structures for regeneration
      following neuronal loss.

PMID- 29174575
TI  - Obeticholic acid protects mice against lipopolysaccharide-induced liver injury
      and inflammation.
AB  - BACKGROUND: Cholestasis, as a main manifestation, induces liver injury during
      sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile
      acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is
      contributed to improve sepsis-induced liver injury remains unknown. OBJECTIVE:
      The aim of the present study was to investigate the effect of OCA on
      lipopolysaccharide (LPS)-induced acute liver injury in mice. RESULTS: 8-week old
      male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA
      group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were
      collected for further analysis. Serum levels of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin
      (TBIL) were measured at indicated time after LPS administration. Liver sections
      were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated
      the expression of FXR and BSEP in livers and protected mice from LPS-induced
      hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced
      higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA
      administration. Meanwhile, the mRNA levels of interleukin 1beta (IL-1beta), tumor
      necrosis factor alpha (TNF-alpha) and IL-6 were decreased in livers of mice in
      LPS + OCA group compared with LPS group. Further investigation indicated that the
      higher expression of ATF4 and LC3II/I were associated with the protective effect
      of OCA on LPS-induced liver injury. CONCLUSION: Orally OCA pretreatment protects
      mice from LPS-induced liver injury possibly contributed by improved bile acid
      homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity
      in hepatocytes.

PMID- 29174576
TI  - DNA binding and Topoisomerase inhibition: How can these mechanisms be explored to
      design more specific anticancer agents?
AB  - DNA is considered one of the most promising targets of molecules with anticancer
      activity potential. Its key role in various cell division mechanisms, which
      commands the intense multiplication of tumor cells, is considered in studies with
      compounds whose mechanisms of action suggest likeliness of interaction. In
      addition, inhibition of enzymes that actively participate in biological functions
      of cells such as Topoisomerase, is seen as a primary factor for conducting
      several events that result in cell death. Discovery of new anticancer
      chemotherapeutical capable of interacting with DNA and inhibiting Topoisomerase
      enzymes is highlighted in anticancer research. The present review aims at showing
      through distinct biological tests the performance of different candidates to
      anticancer drugs and their respective chemical modifications, which are crucial
      and/or determinant for DNA affinity and inhibition of important enzymes in cells'
      vital processe to either separately or synergistically optimize anticancer
      activity.

PMID- 29174577
TI  - Caffeic acid and licochalcone A interfere with the glyoxylate cycle of
      Trichophyton rubrum.
AB  - Trichophyton rubrum is the most common causative agent of dermatomycoses
      worldwide. Despite the increasing incidence of fungal infections, the number of
      commercially available antifungal drugs is limited, mainly because of the
      biochemical similarities between fungal and mammalian cells. Biomolecules of
      different origins might lead to the discovery of new pharmacological targets that
      are more specific to the fungal cell. In this respect, caffeic acid (CA) and
      licochalcone A (LicoA) exhibit activity against some human pathogenic fungi by
      acting on important fungal molecular targets. The glyoxylate cycle is involved in
      the adaptation of fungal cells inside the human cell and is well established for
      some fungi of clinical interest. Activation of this cycle is related to the
      survival of fungi in nutrient-limited environments. However, little is known
      about the involvement of the glyoxylate cycle in this process in dermatophytes.
      The objective of this study was to evaluate the antifungal activity of CA and
      LicoA against T. rubrum, investigating specifically the effect of these compounds
      on important antifungal targets such as ergosterol synthesis, cell wall and
      glyoxylate cycle. The minimum inhibitory concentration was 86.59 MUM for CA and
      11.52 MUM for LicoA. Plasma membrane damage and a reduction in ergosterol levels
      were observed after the exposure of T. rubrum to CA, but not to LicoA. Evaluation
      of gene expression in T. rubrum co-cultured with human keratinocytes (HaCat) in
      the absence of the antifungal compounds showed induction of genes related to the
      ergosterol biosynthesis pathway and genes encoding enzymes involved in cell wall
      synthesis and in the glyoxylate cycle. The same genes were significantly
      repressed after exposure of the co-culture to subinhibitory concentrations of CA
      and LicoA. The enzymatic activity of isocitrate lyase was reduced in the presence
      of LicoA and a moderate reduction was observed in the presence of CA. These
      results indicate that CA and LicoA act on targets that play important roles in
      pathogen-host interactions, in antifungal activity and, especially, in the
      glyoxylate cycle.

PMID- 29174578
TI  - "The Pink Cloud": Can Technology Curb Addiction.

PMID- 29174579
TI  - Factors Affecting the Cost of Radical Cystectomy in the USA: Some Centres Are
      More Equal than Others.

PMID- 29174580
TI  - A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti
      inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal
      Colic.
AB  - CONTEXT: Renal colic is a common, acute presentation of urolithiasis that
      requires immediate pain relief. European Association of Urology guidelines
      recommend nonsteroidal anti-inflammatory drugs (NSAIDs) as the preferred
      analgesia. However, the fear of NSAID adverse effects and the uncertainty about
      superior analgesic effect have maintained the practice of advocating intravenous
      opioids as the initial analgesia. OBJECTIVE: The objective of this systematic
      review and meta-analysis was to compare the safety and efficacy of NSAIDs with
      opioids and paracetamol (acetaminophen) for the management of acute renal colic.
      EVIDENCE ACQUISITION: Cochrane Central Register of Controlled Trials, MEDLINE,
      EMBASE, World Health Organization International Clinical Trials Registry
      Platform, Google Scholar, and the reference list of retrieved articles were
      searched up to December 2016 without language restrictions. Two reviewers
      independently assessed eligible studies using the Cochrane Collaboration tool for
      assessing and reporting the risk of bias and abstracted data using predefined
      data fields. EVIDENCE SYNTHESIS: From 468 potentially relevant studies, 36
      randomized controlled trials (RCTs) including 4887 patients, published between
      1982 and 2016, were included in this systematic review. The treatment effect
      observed indicated marginal benefit of NSAIDs over opioids in initial pain
      reduction at 30min (11 RCTs, n=1985, mean difference [MD] -5.58, 95% confidence
      interval [CI] -10.22 to -0.95; heterogeneity I2=81%). In the subgroup analyses by
      the route of administration, NSAIDs required fewer rescue treatments (seven RCTs,
      n=541, number needed to treat [NNT] 11, 95% CI 6-75) and had lower vomiting rates
      compared with opioids (five RCTs, n=531, NNT 5, 95% CI 4-8). Comparisons of
      NSAIDs with paracetamol showed no difference for both drugs at 30min (four RCTs,
      n=1325, MD -5.67, 95% CI -17.52 to 6.18, p=0.35; I2=89%). Patients treated with
      NSAIDs required fewer rescue treatments (two trials, n=1145, risk ratio 0.56, 95%
      CI 0.42-0.74, p<0.001; I2=0%). CONCLUSIONS: NSAIDs were equivalent to opioids or
      paracetamol in the relief of acute renal colic pain at 30min. There was less
      vomiting and fewer requirements for rescue analgesia with NSAIDs compared with
      opioids. Patients treated with NSAIDs required less rescue analgesia compared
      with paracetamol. Despite observed heterogeneity among the included studies and
      the overall quality of evidence, the findings of a lower need for rescue
      analgesia and fewer adverse events, in conjunction with the practical advantages
      of ease of delivery, suggest that NSAIDs should be the preferred analgesic option
      for patients presenting to the emergency department with renal colic. PATIENT
      SUMMARY: In kidney stone-related acute pain episodes in patients with adequate
      renal function, treatment with nonsteroidal anti-inflammatory drugs offers
      effective and most sustained pain relief, with fewer side effects, when compared
      with opioids or paracetamol.

PMID- 29174581
TI  - Comparison of lung diffusing capacity in young elite athletes and their
      counterparts.
AB  - BACKGROUND: The influence of exercise on the pulmonary function is controverse,
      some studies have reported no sports influence, while the others have found
      positive correlation. AIM: To evaluate and compare the sports influence on
      pulmonary function: spirometry (VC, FVC, FEV1, FEV1/FVC), lung diffusing capacity
      (DLCO) and coefficient of the CO gas transfer (KCO) in two elite athletes groups
      and healthy sedentary controls. METHOD: Equally divided into aerobic and
      anaerobic group, 60 elite athletes were recruited, as well as 43 age-matched,
      healthy sedentary controls. All of the participants performed basic
      anthropometric measurements, spirometry, DLCO and KCO at rest. Kruskal-Wallis one
      way ANOVA test was used to determine differences between groups; Mann-Whitney U
      test was used for inter-groups differences and Pearson coefficient for pulmonary
      variables and anthropometric parameters correlation. Statistical analyses were
      performed using the SPSS computer statistic program, version 20. RESULTS: No
      differences were found in pulmonary characteristics (spirometric function values,
      DLCO and KCO) in athletes and non-athletes at rest, as well as between aerobics
      and anaerobics. There were no correlations between the anthropometric parameters
      and the investigated respiratory function tests. DLCO (%) correlated positively
      with height in athletes playing anaerobic type of sport (karate and taekwondo)
      (p=0.036; r=0.544), and negatively in sedentary control group (p=0.030; r=
      0.560). Regarding KCO, no differences were found. CONCLUSION: Spirometry indices
      and DLCO are not influenced either by aerobic or anaerobic training type, so
      benefits of sports on pulmonary indices or DLCO was not confirmed.

PMID- 29174582
TI  - Macitentan in daily clinical practice: A single centre, 1-year experience.
AB  - The effectiveness and safety of macitentan, a dual endothelin-receptor antagonist
      (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), were
      shown in an extensive clinical trial oriented towards morbidity and mortality
      events. Our aim was to describe a single centre's experience of the utilization
      of macitentan in patients with PAH in clinical practice settings. Thirteen
      patients with different aetiologies and previous PAH treatments were studied.
      After 12 months of macitentan treatment, 11 patients improved their functional
      class (FC), all patients improved their 6-minute walk distance (6MWD) test, and
      10 patients lowered their NT-proBNP plasma levels. Additionally, cardiac imaging
      parameters were also improved. No cases resulted in hospitalization, septostomy,
      transplant or death.

PMID- 29174583
TI  - The protective effects of whortleberry extract against cisplatin-induced
      ototoxicity in rats.
AB  - INTRODUCTION: Cisplatin is one of the main chemotherapeutic agents used for the
      treatment of many types of cancer. However, ototoxicity, one of the most serious
      side effects of cisplatin, restricts its usage. OBJECTIVE: We aimed to
      investigate the protective effects of whortleberry extract against cisplatin
      induced ototoxicity by evaluating hearing and histopathological cochlear damage
      and by measuring the biochemical parameters affected byoxidative stress. METHODS:
      Forty-eight male rats were included in the study after performing Distortion
      Product Otoacoustic Emission test to confirm that their hearing levels were
      normal. The rats were randomly divided into six groups: the control group, the
      sham group, and, which received only whortleberry extract, only cisplatin,
      cisplatin+100mg whortleberry extract, cisplatin+200mg whortleberry extract,
      respectively. Audiologic investigation was performed by performing the Distortion
      Product Otoacoustic Emission test at the beginning and at the eighth day of the
      study. Cardiac blood samples were collected for biochemical analysis, and the
      rats were sacrificed to obtain cochlear histopathological specimens on the eighth
      day. RESULTS: The results revealed that whortleberry protects hearing against
      cisplatin-induced ototoxicity independent of the dose. However, high doses of
      whortleberry extract are needed to prevent histopathological degeneration and
      oxidative stress. CONCLUSION: The results obtained in this study show that
      whortleberry extract has a protective effect against cisplatin-induced
      ototoxicity.

PMID- 29174584
TI  - Vocal assessment of addicts on methadone therapy via the RBH scale and objective
      acoustic parameters.
AB  - INTRODUCTION: A large number of people around the world struggle daily to become
      free of their addiction to illegal psychoactive substances. In order to create an
      atmosphere of improved supervision, established communication and improved
      quality of life for drug addicts, centers have been set up to provide methadone
      as a substitute. OBJECTIVE: The aim of the research was to assess the vocal
      features of drug addicts on methadone therapy via subjective and objective
      parameters, to ascertain if vocal damage has occurred and to determine whether
      subjective and objective acoustic vocal parameters are related, and how. METHODS:
      The research included 34 adults of both genders who were undergoing methadone
      treatment. A subjective vocal evaluation assessed voice pitch and clarity, while
      the subjective acoustic analysis utilized the Roughness-Breathiness-Hoarseness
      scale of roughness-breathiness-hoarseness. Objective acoustic analysis was
      conducted after recording and analyzing an uninterrupted vocal /a/ of at least
      three seconds duration, using the "GllotisController" software. RESULTS: The
      subjective acoustic analysis using the Roughness-Breathiness-Hoarseness scale
      showed pathological values in 52.9% male and 47% female participants. The average
      values of the roughness-breathiness-hoarseness for the entire sample were 0.91,
      0.38 and 0.50, respectively. Lower roughness was associated with a higher
      fundamental frequency (f0) and lower jitter and shimmer values (p<0.05). There
      was a statistically significant correlation between breathiness, jitter (p<0.01)
      and shimmer (p<0.05), and between hoarseness and jitter (p<0.01). CONCLUSION: A
      statistically significant correlation was found between the two subjective vocal
      assessments, voice clarity and pitch, and Roughness-Breathiness-Hoarseness scale,
      and the parameters of the objective acoustic vocal assessment.

PMID- 29174585
TI  - Current Trends and Future Perspectives in the Treatment of Pulmonary Arterial
      Hypertension.
AB  - Pulmonary hypertension continues to be a life-threatening illness with
      debilitating physical and emotional consequences affecting around 1% of global
      population. The progression of this devastating disease is characterized by
      increase in pulmonary vascular resistance resulting in elevated pulmonary
      pressure, eventually leading to right heart failure and death. Better
      understanding of pathophysiology has led to substantial improvements in terms of
      availability of treatment options. The purpose of this review is to summarize the
      currently available treatment options along with pertinent trials and possible
      future therapies of pulmonary arterial hypertension.

PMID- 29174586
TI  - Aortic Valve Regurgitation: A Comprehensive Review.
AB  - Aortic regurgitation (AR) has an estimated prevalence of 4.9% in the Framingham
      study, with moderate or severe AR occurring in 0.5% of the study population. The
      incidence and severity of AR increases with age, and may occur acutely or as a
      chronic valvular disease with distinct presentations, natural history and
      management strategy. Our review is a comprehensive description of the varied
      presentation of aortic regurgitation and its management.

PMID- 29174587
TI  - Effects of mesenchymal stromal cells play a role the oxidant/antioxidant balance
      in a murine model of asthma.
AB  - Asthma is a heterogeneous disease characterised by chronic airway inflammation.
      One of the most devastating consequences of this inflammatory process is the
      generation of reactive oxygen and nitrogen species responsible for oxidative
      stress. The aim of this study is to analyse the efficiency of treatment with
      human bone marrow-derived mesenchymal stromal cells (hMSC) in maintaining the
      oxidative balance in a murine model of allergic asthma by quantifying
      nitrotyrosine in lung tissues. After confirmation of asthma in the experimental
      model, samples of lung parenchyma were submitted to immunohistochemical
      assessment. Intravenous administration of hMSC reduced the levels of
      nitrotyrosine in the ASTHMA-hMSC group compared to those in the ASTHMA-SAL group.
      In conclusion, therapeutic administration of hMSC had a beneficial effect on
      oxidative stress, reducing the levels of nitrotyrosine in lung tissues in a model
      of allergic asthma.

PMID- 29174588
TI  - Trimethylene carbonate-caprolactone conduit with poly-p-dioxanone microfilaments
      to promote regeneration after spinal cord injury.
AB  - : Spinal cord injury (SCI) is often associated with scarring and cavity formation
      and therefore bridging strategies are essential to provide a physical substrate
      for axonal regeneration. In this study we investigated the effects of a
      biodegradable conduit made from trimethylene carbonate and epsilon-caprolactone
      (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves
      on regeneration after SCI in adult rats. In vitro studies demonstrated that
      different cell types including astrocytes, meningeal fibroblasts, Schwann cells
      and adult sensory dorsal root ganglia neurons can grow on the TC and PDO
      material. For in vivo experiments, the TC/PDO conduit was implanted into a small
      2-3 mm long cavity in the C3-C4 cervical segments immediately after injury (acute
      SCI) or at 2-5 months after initial surgery (chronic SCI). At 8 weeks after
      implantation into acute SCI, numerous 5HT-positive descending raphaespinal axons
      and sensory CGRP-positive axons regenerated across the conduit and were often
      associated with PDO microfilaments and migrated host cells. Implantation into
      chronically injured SCI induced regeneration mainly of the sensory CGRP-positive
      axons. Although the conduit had no effect on the density of OX42-positive
      microglial cells when compared with SCI control, the activity of GFAP-positive
      astrocytes was reduced. The results suggest that a TC/PDO conduit can support
      axonal regeneration after acute and chronic SCI even without addition of
      exogenous glial or stem cells. STATEMENT OF SIGNIFICANCE: Biosynthetic conduits
      can support regeneration after spinal cord injury but often require addition of
      cell therapy and neurotrophic factors. This study demonstrates that biodegradable
      conduits made from trimethylene carbonate and epsilon-caprolactone with poly-p
      dioxanone microfilaments alone can promote migration of different host cells and
      stimulate axonal regeneration after implantation into acute and chronic spinal
      cord injury. These results can be used to develop biosynthetic conduits for
      future clinical applications.

PMID- 29174589
TI  - Focal adhesion signaling affects regeneration by human nucleus pulposus cells in
      collagen- but not carbohydrate-based hydrogels.
AB  - : Hydrogel-based 3D cell cultures are an emerging strategy for the regeneration
      of cartilage. In an attempt to regenerate dysfunctional intervertebral discs,
      nucleus pulposus (NP) cells can be cultured in hydrogels of various kinds and
      physical properties. Stiffness sensing through focal adhesions is believed to
      direct chondrogenesis, but the mechanisms by which this works are largely
      unknown. In this study we compared focal adhesion formation and glycosaminoglycan
      (GAG) deposition by NP cells in a range of hydrogels. Using a focal adhesion
      kinase (FAK) inhibitor, we demonstrated that focal adhesion signaling is involved
      in the response of NP cells in hydrogels that contain integrin binding sites
      (i.e. methacrylated gelatin (gelMA) and type II collagen), but not in hydrogels
      deplete from integrin binding sites such as alginate and agarose, or CD44-binding
      hydrogels based on hyaluronic acid. As a result of FAK inhibition we
      observedenhanced proteoglycan production in gelMA, but decreased production in
      type II collagen hydrogels, which could be explained by alteration in cell fate
      as supported by the increase in the adipogenic marker peroxisome proliferator
      activated receptor gamma (PPARy). Furthermore, GAG deposition was inversely
      proportional to polymer concentration in integrin-binding gelMA, while no direct
      relationship was found for the non-integrin binding gels alginate and agarose.
      This corroborates our finding that focal adhesion formation plays an important
      role in NP cell response to its surrounding matrix. STATEMENT OF SIGNIFICANCE:
      Biomaterials are increasingly being investigated for regenerative medicine
      applications, including regeneration of the nucleus pulposus. Cells interact with
      their environment and are influenced by extracellular matrix or polymer
      properties. Insight in these interactions can improve regeneration and helps to
      understand degeneration processes. The role of focal adhesion formation in the
      regenerative response of nucleus pulposus cells is largely unknown. Therefore,
      the relation between materials, stiffness and focal adhesion formation is studied
      here.

PMID- 29174590
TI  - Double outlet right ventricle with subpulmonary ventricular septal defect
      (Taussig-Bing anomaly) and other complex congenital cardiac malformations in an
      American Quarter Horse foal.
AB  - A 4-week-old American Quarter Horse colt presented with a recent history of
      diarrhea and decreased activity level. On initial physical examination, the
      animal was bright and alert and major findings were limited to a loud systolic
      heart murmur radiating widely over both sides of the thorax. While in the
      hospital, the clinical condition of the foal warranted further imaging to
      determine the cause and extent of cardiac disease. A variety of congenital
      cardiac malformations were identified during echocardiographic examination and
      autopsy, including a double outlet right ventricle and a subpulmonary
      interventricular septal defect (Taussig-Bing anomaly), ventricular inversion with
      atrioventricular discordance, tricuspid valve atresia, a septum primum
      interatrial septal defect, mitral valve dysplasia with a cleft in the septal
      mitral valve cusp, aortic, and subaortic stenosis, tubular hypoplasia of the
      ascending aorta and the aortic arch, a patent ductus arteriosus, an aberrant
      circumflex coronary artery, and aberrant left and right subclavian arteries.
      Echocardiographic and postmortem findings of the cardiac defects in this foal are
      presented and discussed.

PMID- 29174591
TI  - Antidepressants Rescue Stress-Induced Disruption of Synaptic Plasticity via
      Serotonin Transporter-Independent Inhibition of L-Type Calcium Channels.
AB  - BACKGROUND: Long-term synaptic plasticity is a basic ability of the brain to
      dynamically adapt to external stimuli and regulate synaptic strength and
      ultimately network function. It is dysregulated by behavioral stress in animal
      models of depression and in humans with major depressive disorder.
      Antidepressants have been shown to restore disrupted synaptic plasticity in both
      animal models and humans; however, the underlying mechanism is unclear. METHODS:
      We examined modulation of synaptic plasticity by selective serotonin reuptake
      inhibitors (SSRIs) in hippocampal brain slices from wild-type rats and serotonin
      transporter (SERT) knockout mice. Recombinant voltage-gated calcium (Ca2+)
      channels in heterologous expression systems were used to determine the modulation
      of Ca2+ channels by SSRIs. We tested the behavioral effects of SSRIs in the
      chronic behavioral despair model of depression both in the presence and in the
      absence of SERT. RESULTS: SSRIs selectively inhibited hippocampal long-term
      depression. The inhibition of long-term depression by SSRIs was mediated by a
      direct block of voltage-activated L-type Ca2+ channels and was independent of
      SERT. Furthermore, SSRIs protected both wild-type and SERT knockout mice from
      behavioral despair induced by chronic stress. Finally, long-term depression was
      facilitated in animals subjected to the behavioral despair model, which was
      prevented by SSRI treatment. CONCLUSIONS: These results showed that
      antidepressants protected synaptic plasticity and neuronal circuitry from the
      effects of stress via a modulation of Ca2+ channels and synaptic plasticity
      independent of SERT. Thus, L-type Ca2+ channels might constitute an important
      signaling hub for stress response and for pathophysiology and treatment of
      depression.

PMID- 29174592
TI  - Common Neurotransmission Recruited in (R,S)-Ketamine and (2R,6R)
      Hydroxynorketamine-Induced Sustained Antidepressant-like Effects.

PMID- 29174594
TI  - Prediction of filamentous process performance attributes by CSL quality
      assessment using mid-infrared spectroscopy and chemometrics.
AB  - Every biopharmaceutical production process aims for control strategies to achieve
      process robustness in order to ensure consistent product quality. Process
      variability can origin from process parameters, the biological nature as well as
      from high lot-to-lot variability of raw materials. In filamentous processes raw
      materials with very complex matrices, such as corn steep liquor (CSL), are used,
      which are especially challenging to characterize. In this study, CSL was
      characterized in detail for its ingredients presenting an overall composition of
      its matrix of 50 analyzed components (19 amino acids, 5 organic acids, 8 reducing
      sugars, 7 water-soluble vitamins and 11 trace elements/minerals) in order to
      facilitate analytical reduction to fingerprinting methods FT-MIR was evaluated as
      fast and non-destructive spectroscopic fingerprinting method for adequate
      assessment of CSL quality. Feasibility of this method was shown by the
      correlation of certain bands in the spectra to substance groups present in CSL,
      such as the Amide I and II band and amino acids, respectively. Additionally,
      applicability of FT-MIR could be shown for classification of different CSL lots
      differing in provider and corn quality as well as for predictability of process
      performance attributes. The latter was demonstrated on a fed-batch filamentous
      fungi process for the production of antibiotics. By multivariate data analysis,
      it could be shown that CSL quality assessment via FT-MIR can be used for the
      prediction of maximal biomass generated in the process, with a correlation
      coefficient R2 of 0.964, as well as for the prediction of an unwanted impurity.
      The combination of a fast and easy method for CSL quality assessment and
      correlations of this quality with process performance attributes may facilitate
      the establishment of a risk-based acceptance criteria for raw material quality
      release of CSL. As CSL is a frequent used raw material, we believe that this
      method will also be useful for other processes and that CSL quality assessment is
      of high relevance in academia and industry.

PMID- 29174595
TI  - Impact of everolimus-eluting stent length on long-term clinical outcomes of
      percutaneous coronary intervention.
AB  - BACKGROUND: Even though longer stented lengths may increase the risk of
      restenosis, full coverage of diffuse long lesions with longer stents seems to be
      the optimal strategy for percutaneous coronary intervention (PCI) in the new drug
      eluting stent (DES) era. However, it remains unclear whether this strategy will
      indicate favorable outcome or not. This study evaluated the impact of stent
      length on two-year clinical outcomes after PCI with the XIENCE Alpine everolimus
      eluting stent. METHODS: This was a retrospective, non-randomized, observational
      study. Four patient groups were classified according to implanted overall total
      stent length (short, <15mm; middle, 15-23mm; long, 24-32mm; and ultra-long,
      >32mm). The primary outcome of this study was major adverse cardiac events
      (MACE), defined as the composite of cardiac death, recurrent myocardial
      infarction (MI), target vessel revascularization (TVR), and stent thrombosis
      (ST). Angiographic restenosis by quantitative coronary angiography was defined as
      >50% diameter stenosis at 10 months after PCI. RESULTS: A total of 730 patients
      who received intravascular ultrasound (IVUS)-guided PCI were enrolled. The short,
      middle, long, and ultra-long stent groups included 138 patients (149 lesions),
      210 patients (235 lesions), 190 patients (209 lesions), and 192 patients (208
      lesions), respectively. The primary outcome at two years did not differ among the
      four groups (MACE: 4.4% in short, 3.3% in middle, 4.7% in long, and 4.7% in ultra
      long groups, p=0.402); TVR, ST, MI, and cardiac mortality also did not differ
      among groups. CONCLUSIONS: Long stenting using the XIENCE stent which was guided
      by IVUS for diffuse, long lesions was associated with favorable clinical outcomes
      at two years in daily clinical practice.

PMID- 29174596
TI  - Author's reply.

PMID- 29174593
TI  - Brain Regions Showing White Matter Loss in Huntington's Disease Are Enriched for
      Synaptic and Metabolic Genes.
AB  - BACKGROUND: The earliest white matter changes in Huntington's disease are seen
      before disease onset in the premanifest stage around the striatum, within the
      corpus callosum, and in posterior white matter tracts. While experimental
      evidence suggests that these changes may be related to abnormal gene
      transcription, we lack an understanding of the biological processes driving this
      regional vulnerability. METHODS: Here, we investigate the relationship between
      regional transcription in the healthy brain, using the Allen Institute for Brain
      Science transcriptome atlas, and regional white matter connectivity loss at three
      time points over 24 months in subjects with premanifest Huntington's disease
      relative to control participants. The baseline cohort included 72 premanifest
      Huntington's disease participants and 85 healthy control participants. RESULTS:
      We show that loss of corticostriatal, interhemispheric, and intrahemispheric
      white matter connections at baseline and over 24 months in premanifest
      Huntington's disease is associated with gene expression profiles enriched for
      synaptic genes and metabolic genes. Corticostriatal gene expression profiles are
      predominately associated with motor, parietal, and occipital regions, while
      interhemispheric expression profiles are associated with frontotemporal regions.
      We also show that genes with known abnormal transcription in human Huntington's
      disease and animal models are overrepresented in synaptic gene expression
      profiles, but not in metabolic gene expression profiles. CONCLUSIONS: These
      findings suggest a dual mechanism of white matter vulnerability in Huntington's
      disease, in which abnormal transcription of synaptic genes and metabolic
      disturbance not related to transcription may drive white matter loss.

PMID- 29174598
TI  - Acute coronary syndrome - Still a valid contraindication to perform rotational
      atherectomy? Early and one-year outcomes.
AB  - BACKGROUND: Rotational atherectomy (RA) is an acknowledged method of percutaneous
      treatment of highly calcified or fibrotic coronary lesions. However, using the
      rotablator system in patients presenting with acute coronary syndromes (ACS)
      remains controversial and is considered as a relative contraindication. The aim
      of our study was to assess in-hospital and 1-year outcomes in patients undergoing
      RA presenting with ACS, in comparison to elective RA procedures. METHODS: This
      single-center observational study included all consecutive patients who underwent
      RA and PCI in our institution from April 2008 to October 2015. All patients were
      subsequently divided into two groups based on clinical presentation: stable
      angina group (SA) and ACS group. Primary endpoints were in-hospital and 1-year
      all-cause mortality and 1-year major adverse cardiac events (MACE). Secondary
      endpoints were procedural success and in-hospital complications. RESULTS: The
      study included 207 patients, 164 (79%) in SA group and 43 (21%) in ACS group. In
      hospital mortality was higher in patients with ACS (4.7% vs. 0%, p=0.01).
      Procedural success was similar in both groups, 93% in ACS groups vs. 92.7% in SA
      group, p=0.94. There were no significant differences in the rate of
      periprocedural complications (4.7% vs. 10.4%, p=0.25), however postprocedural
      complications were more frequent in ACS group. At 1-year follow-up MACE rate and
      mortality were numerically higher, however statistically not significant (25.6%
      vs. 16.5%, p=0.17 and 16.3% vs. 7.9%, p=0.10; respectively). CONCLUSIONS: Despite
      higher mortality and complication rate in ACS group observed in postprocedural
      period, we found no significant difference in 1-year outcomes in comparison to
      elective patients. Procedural success of RA in ACS patients is similar to
      elective patients with SA and this procedure should be considered in case of
      urgent indications, if no other options of treatment exist.

PMID- 29174597
TI  - Intravascular hemolysis in patients with mitral regurgitation: Evaluation by
      erythrocyte creatine.
AB  - BACKGROUND: Intravascular hemolysis has been reported in patients with cardiac
      valve prostheses, but intravascular hemolysis in patients with mitral
      regurgitation with native valve has not been evaluated in detail. We designed a
      study to elucidate the impact of regurgitation flow on intravascular hemolysis in
      patients with primary mitral regurgitation by measuring erythrocyte creatine.
      METHODS: Erythrocyte creatine was enzymatically assayed in 29 patients with
      moderate to severe primary mitral regurgitation and 12 age-matched healthy
      volunteers. The size and characteristics of mitral regurgitation were determined
      by color Doppler echocardiography. RESULTS: Erythrocyte creatine was
      significantly higher in patients with eccentric jet (n=17, 2.64+/-0.77MUmol/g Hb)
      than that of central jet (n=12, 1.68+/-0.13MUmol/g Hb) and control subjects
      (1.39+/-0.25MUmol/g Hb). Patients with eccentric jet had a significantly lower
      erythrocyte count and hemoglobin (385+/-58 x104/MUL and 116+/-19g/l) compared to
      those with central jet (450+/-47*104/MUL and 137+/-14g/l) and control subjects
      (433+/-31*104/MUL and 134+/-19g/l). There were no significant differences in age,
      estimated glomerular filtration rate, pulmonary artery systolic pressure, left
      atrial size and left ventricular end-diastolic dimension between patients with
      eccentric jet and central jet. CONCLUSIONS: Intravascular hemolysis associated
      with subclincal anemia in patients with eccentric jet was due to the destruction
      of erythrocyte by collision of the eccentric jet to the atrial wall.

PMID- 29174599
TI  - Strategy of delayed surgery for ventricular septal perforation after acute
      myocardial infarction.
AB  - BACKGROUND: The timing of surgical repair for ventricular septal perforation
      (VSP) is important because patients are susceptible to bleeding from fragile
      myocardial tissue or residual shunt during the acute phase of acute myocardial
      infarction (AMI). This study aimed to assess the results of delayed surgery for
      VSP performed 2 weeks after AMI. METHODS: In total, 24 consecutive postinfarction
      patients with VSP (mean age: 72.6+/-10.4 years; 13 males) underwent operation
      between May 2003 and June 2016. We postponed surgery during the acute phase and
      performed an elective surgery if the patient could wait for 2 weeks with support
      from intra-aortic balloon pumping (IABP) and respiratory management. If we could
      not control heart failure and organ function worsened during that period, we
      performed emergency surgery. Postoperative outcomes included complications, 30
      day mortality rate, long-term hospital death, reoperation rate, and risk factors
      for hospital mortality. We examined whether organ function was maintained by
      delaying the surgery. RESULTS: Of the 24 patients, 11 (45.8%) required emergency
      surgery, and 13 (54.2%) could wait 2 weeks for surgery. The average time from AMI
      onset to diagnosis of VSP was 4.5+/-1.6 days, and the average time from VSP
      diagnosis to surgery was 9.0+/-6.0 days; 5 patients (20.8%) required resurgery
      for VSP due to residual shunt, recurrent VSP, or pseudoaneurysm of the left
      ventricle. The 30-day mortality rate was 4.2% (1 patient), and long-term hospital
      mortality rate was 12.5% (3 patients). Organ function was maintained in 10
      patients (76.9%) who underwent elective surgery, and organ dysfunction was not
      advanced by delaying the surgery. CONCLUSIONS: We could delay surgery for an
      average of 9 days from VSP onset by means of IABP or respiratory management
      without the deterioration of organ function. The 30-day mortality and long-term
      outcome were favorable.

PMID- 29174600
TI  - Hybrid combinations containing natural products and antimicrobial drugs that
      interfere with bacterial and fungal biofilms.
AB  - BACKGROUND: Biofilms contribute to the pathogenesis of many chronic and difficult
      to eradicate infections whose treatment is complicated due to the intrinsic
      resistance to conventional antibiotics. As a consequence, there is an urgent need
      for strategies that can be used for the prevention and treatment of biofilm
      associated infections. The combination therapy comprising an antimicrobial drug
      with a low molecular weight (MW) natural product and an antimicrobial drug
      (antifungal or antibacterial) appeared as a good alternative to eradicate
      biofilms. PURPOSE: The aims of this review were to perform a literature search on
      the different natural products that have showed the ability of potentiating the
      antibiofilm capacity of antimicrobial drugs, to analyze which are the
      antimicrobial drugs most used in combination, and to have a look on the microbial
      species most used to prepare biofilms. RESULTS: Seventeen papers, nine on
      combinations against antifungal biofilms and eight against antibacterial biofilms
      were collected. Within the text, the following topics have been developed: breaf
      history of the discovery of biofilms; stages in the development of a biofilm; the
      most used methodologies to assess antibiofilm-activity; the natural products with
      capacity of eradicating biofilms when acting alone; the combinations of low MW
      natural products with antibiotics or antifungal drugs as a strategy for
      eradicating microbial biofilms and a list of the low MW natural products that
      potentiate the inhibition capacity of antifungal and antibacterial drugs against
      biofilms. CONCLUSIONS AND PERSPECTIVES: Regarding combinations against antifungal
      biofilms, eight over the nine collected works were carried out with in vitro
      studies while only one was performed with in vivo assays by using Caenorhabditis
      elegans nematode. All studies use biofilms of the Candida genus. A 67% of the
      potentiators were monoterpenes and sesquiterpenes and six over the nine works
      used FCZ as the antifungal drug. The activity of AmpB and Caspo was enhanced in
      one and two works respectively. Regarding combinations against bacterial
      biofilms, in vitro studies were performed in all works by using several different
      methods of higher variety than the used against fungal biofilms. Biofilms of both
      the gram (+) and gram (-) bacteria were prepared, although biofilm of
      Staphylococcus spp. were the most used in the collected works. Among the
      discovered potentiators of antibacterial drugs, 75% were terpenes, including
      mono, di- and triterpenes, and, among the atibacterial drugs, several
      structurally diverse types were used in the combinations: aminoglycosides, beta
      lactams, glucopeptides and fluoroquinolones. The potentiating capacity of natural
      products, mainly terpenes, on the antibiofilm effect of antimicrobial drugs opens
      a wide range of possibilities for the combination antimicrobial therapy. More in
      vivo studies on combinations of natural products with antimicrobial drugs acting
      against biofilms are highly required to cope the difficult to treat biofilm
      associated infections.

PMID- 29174601
TI  - Food-derived 1,2-dicarbonyl compounds and their role in diseases.
AB  - Reactive 1,2-dicarbonyl compounds (DCs) are generated from carbohydrates during
      food processing and storage and under physiological conditions. In the recent
      decades, much knowledge has been gained concerning the chemical formation
      pathways and the role of DCs in food and physiological systems. DCs are formed
      mainly by dehydration and redox reactions and have a strong impact on the
      palatability of food, because they participate in aroma and color formation.
      However, they are precursors of advanced glycation end products (AGEs), and
      cytotoxic effects of several DCs have been reported. The most abundant DCs in
      food are 3-deoxyglucosone, 3-deoxygalactosone, and glucosone, predominating over
      methylglyoxal, glyoxal, and 3,4-dideoxyglucosone-3-ene. The availability for
      absorption of individual DCs is influenced by the release from the food matrix
      during digestion and by their reactivity towards constituents of intestinal
      fluids. Some recent works suggest formation of DCs from dietary sugars after
      their absorption, and others indicate that certain food constituents may scavenge
      endogenously formed DCs. First works on the interplay between dietary DCs and
      diseases reveal an ambiguous role of the compounds. Cancer-promoting but also
      anticancer effects were ascribed to methylglyoxal. Further work is still needed
      to elucidate the reactions of DCs during intestinal digestion and
      pathophysiological effects of dietary DCs at doses taken up with food and in
      "real" food matrices in disease states such as diabetes, uremia, and cancer.

PMID- 29174602
TI  - Editorial Comment.

PMID- 29174604
TI  - Editorial Comment.

PMID- 29174605
TI  - Insecticidal activity of the metalloprotease AprA occurs through suppression of
      host cellular and humoral immunity.
AB  - The biochemical characterization of virulence factors from entomopathogenic
      bacteria is important to understand entomopathogen-insect molecular interactions.
      Pseudomonas entomophila is a typical entomopathogenic bacterium that harbors
      virulence factors against several insects. However, the molecular actions of
      these factors against host innate immune responses are not clearly elucidated. In
      this study, we observed that bean bugs (Riptortus pedestris) that were injected
      with P. entomophila were highly susceptible to this bacterium. To determine how
      P. entomophila counteracts the host innate immunity to survive within the insect,
      we purified a highly enriched protein with potential host insect-killing activity
      from the culture supernatant of P. entomophila. Then, a 45-kDa protein was
      purified to homogeneity and identified as AprA which is an alkaline zinc
      metalloprotease of the genus Pseudomonas by liquid chromatography mass
      spectrometry (LC-MS). Purified AprA showed a pronounced killing effect against
      host insects and suppressed both host cellular and humoral innate immunity.
      Furthermore, to show that AprA is an important insecticidal protein of P.
      entomophila, we used an aprA-deficient P. entomophila mutant strain (DeltaaprA).
      When DeltaaprA mutant cells were injected to host insects, this mutant exhibited
      extremely attenuated virulence. In addition, the cytotoxicity against host
      hemocytes and the antimicrobial peptide-degrading ability of the DeltaaprA mutant
      were greatly decreased. These findings suggest that AprA functions as an
      important insecticidal protein of P. entomophila via suppression of host cellular
      and humoral innate immune responses.

PMID- 29174606
TI  - Driving behavior recognition using EEG data from a simulated car-following
      experiment.
AB  - Driving behavior recognition is the foundation of driver assistance systems, with
      potential applications in automated driving systems. Most prevailing studies have
      used subjective questionnaire data and objective driving data to classify driving
      behaviors, while few studies have used physiological signals such as
      electroencephalography (EEG) to gather data. To bridge this gap, this paper
      proposes a two-layer learning method for driving behavior recognition using EEG
      data. A simulated car-following driving experiment was designed and conducted to
      simultaneously collect data on the driving behaviors and EEG data of drivers. The
      proposed learning method consists of two layers. In Layer I, two-dimensional
      driving behavior features representing driving style and stability were selected
      and extracted from raw driving behavior data using K-means and support vector
      machine recursive feature elimination. Five groups of driving behaviors were
      classified based on these two-dimensional driving behavior features. In Layer II,
      the classification results from Layer I were utilized as inputs to generate a k
      Nearest-Neighbor classifier identifying driving behavior groups using EEG data.
      Using independent component analysis, a fast Fourier transformation, and linear
      discriminant analysis sequentially, the raw EEG signals were processed to extract
      two core EEG features. Classifier performance was enhanced using the adaptive
      synthetic sampling approach. A leave-one-subject-out cross validation was
      conducted. The results showed that the average classification accuracy for all
      tested traffic states was 69.5% and the highest accuracy reached 83.5%,
      suggesting a significant correlation between EEG patterns and car-following
      behavior.

PMID- 29174607
TI  - Upregulation of SERT and ADORA1 in broilers with acute right ventricular failure.
AB  - Pulmonary hypertension (PH), remains a challenging disease with a large impact on
      both humans and meat-type chickens. PH is characterized by the onset of
      idiopathic pulmonary arterial hypertension leading to right ventricular failure.
      In this experiment relative gene expression of adenosine A1 receptor (ADORA1),
      serotonin transporter (SERT), phosphodiesterase 5A (PDE5) and troponin T2 were
      compared in hearts from broilers with acute right ventricular failure and from
      healthy birds. There were major increases in adenosine A1 receptor (177%) and
      serotonin transporter (475%), and more modest but significant increases in PDE5
      (146%) and troponin T2 (140%) gene expressions in broilers with right ventricular
      failure compared to healthy birds (P<0.01). This novel report shows that
      pulmonary hypertension related gene expression in broilers is similar to that in
      humans. This molecular similarity between PH in broilers and human patients
      suggests, first, that they will make a suitable animal model for study PH in
      humans, but also that the literature on PH in humans may be profitably applied to
      the study of PH in broilers.

PMID- 29174608
TI  - Effect of surfactants and hydrophilic polymers on the stability of an
      antihypertensive drug candesartan cilexetil: Evaluation by HPLC.
AB  - OBJECTIVES: The objective of this study is to investigate the effect of
      surfactants (polysorbate 80 and sodium lauryl sulphate) and hydrophilic polymers
      (polyvinylpyrrolidone and polyethylene glycol 6000) on the stability of
      candesartan cilexetil under isothermal stress conditions (100 degrees C, 48h).
      METHODS: HPLC method was employed to evaluate the drug content and formation of
      degradation products in stress samples. Drug and degradation products were
      separated on Hypersil BDS C18 (250*4.6mm, 5MU) column using acetonitrile-water
      (pH 2.8) in the ratio of 85:15% v/v as a mobile phase. RESULT: Similar
      degradation behaviour of drug was observed with polyvinylpyrrolidone,
      polyethylene glycol 6000 and polysorbate 80; four common degradation peaks were
      observed at the retention time of 3.7, 4.5, 7.8 and 11minutes. One extra common
      degradation peak of very low intensity was also observed with polyethylene glycol
      6000 and polysorbate 80 at the retention time of 4.2min. The drug was eluting at
      the retention time of 5.4min. In the case of sodium lauryl sulphate, two
      prominent degradation peaks were observed at the retention time of 3.7 and
      13.25min along with few very low-intensity degradation peaks. CONCLUSION: The
      drug showed 41%, 64%, 72% and 98% degradation in presence of
      polyvinylpyrrolidone, polyethylene glycol 6000, polysorbate 80 and sodium lauryl
      sulphate, respectively.

PMID- 29174609
TI  - [Impact of an automated dispensing system for medical devices in cardiac surgery
      department].
AB  - To secure medical devices' management, the implementation of automated dispensing
      system in surgical service has been realized. The objective of this study was to
      evaluate security, organizational and economic impact of installing automated
      dispensing system for medical devices (ASDM). The implementation took place in a
      cardiac surgery department. Security impact was assessed by comparing
      traceability rate of implantable medical devices one year before and one year
      after installation. Questionnaire on nurses' perception and satisfaction
      completed this survey. Resupplying costs, stocks' evolution and investments for
      the implementation of ASDM were the subject of cost-benefit study. After one
      year, traceability rate is excellent (100%). Nursing staffs were satisfied with
      87.5% by this new system. The introduction of ASDM allowed a qualitative and
      quantitative decrease in stocks, with a reduction of 30% for purchased medical
      devices and 15% for implantable medical devices in deposit-consignment. Cost
      benefit analysis shows a rapid return on investment. Real stock decrease
      (purchased medical devices) is equivalent to 46.6% of investment. Implementation
      of ASDM allows to secure storage and dispensing of medical devices. This system
      has also an important economic impact and appreciated by users.

PMID- 29174610
TI  - Toxoplasma and Africa: One Parasite, Two Opposite Population Structures.
AB  - Exploring the genetic diversity of Toxoplasma gondii is essential for an
      understanding of its worldwide distribution and the determinants of its
      evolution. Africa remains one of the least studied areas of the world regarding
      T. gondii genetic diversity. This review has compiled published data on T. gondii
      strains from Africa to generate a comprehensive map of their continent-wide
      geographical distribution. The emerging picture about T. gondii strain
      distribution in Africa suggests a geographical separation of the parasite
      populations across the continent. We discuss the potential role of a number of
      factors in shaping this structure. We finally suggest the next steps towards a
      better understanding of Toxoplasma epidemiology in Africa in light of the strains
      circulating on this continent.

PMID- 29174611
TI  - Preventing tuberculosis-related death in children with HIV.

PMID- 29174613
TI  - Oncologic Safety of Robotic Partial Nephrectomy: Setting Tiles in the Mosaic of
      Evidence While Designing Future Research Projects.

PMID- 29174614
TI  - Marketing and Testosterone Treatment in the USA: A Systematic Review.
AB  - CONTEXT: Testosterone replacement therapy (TRT) is currently approved by the Food
      and Drug Administration only for classic hypogonadism, although off-label
      indications have resulted in a dramatic expansion in prescriptions in the USA.
      Marketing may significantly affect prescriber behavior. OBJECTIVE: To
      systematically review all available evidence on marketing and TRT in the USA.
      EVIDENCE ACQUISITION: PubMed, Embase, and Scopus were searched up to July 2017
      for all relevant publications reporting on assessments of the TRT market size,
      economic costs associated with hypogonadism, trends in TRT prescriptions, drug
      discontinuation rates, and advertising and sales efforts in the USA. EVIDENCE
      SYNTHESIS: Twenty retrospective studies were included in the final analysis. The
      market size for hypogonadism constitutes 5.6-76.8% of men in the USA, with the
      lower end of the range representing the strictest criteria for diagnosis. Men
      with a diagnosis of hypogonadism consume $14 118 in direct and indirect costs to
      the payer. Over the last 2 decades, TRT prescriptions have increased between 1.8-
      and 4-fold. After 1 yr, 80-85% of men discontinue TRT. There is an association
      between direct-to-consumer advertising and testosterone testing, TRT
      prescriptions, and TRT without testosterone testing. There is a high prevalence
      of misinformation on Internet advertising. CONCLUSIONS: Off-label indications
      have driven the dramatic expansion of TRT prescriptions over the last 2 decades.
      Direct-to-consumer advertising poses a unique challenge in the USA. Overtreatment
      can be avoided by applying strict diagnostic criteria for hypogonadism, which
      limits the addressable market for TRT. PATIENT SUMMARY: In this report, we
      reviewed the relationship between marketing and testosterone therapy in the USA.
      We found that many patients are prescribed testosterone without an appropriate
      diagnosis of hypogonadism, which may be related to the marketing efforts for off
      label prescribing.

PMID- 29174615
TI  - Can Focal Treatment Replace Radical Treatment in Prostate Cancer? For Focal
      Therapy.

PMID- 29174616
TI  - Surgical Treatment of Male Postprostatectomy Incontinence: Current Concepts.
AB  - CONTEXT: Radical prostatectomy is the most common reason for male stress urinary
      incontinence. There is still insecurity about its therapeutic management.
      OBJECTIVE: To evaluate current evidence regarding therapy of postprostatectomy
      incontinence (PPI). EVIDENCE ACQUISITION: In October 2017, a nonsystematic review
      of the literature published within the last 2 yr was performed using the
      PubMed/Medline database. In total, 58 articles were included in the current
      analysis. EVIDENCE SYNTHESIS: Regarding invasive management of moderate-to-severe
      PPI, artificial urinary sphincter (AUS) is still the treatment of choice. Recent
      studies focused on efficacy, but also a plethora of potential predictive features
      for treatment success has been investigated. Owing to inconsistent results, there
      still is no consensus about valid risk factors of AUS treatment success to date.
      There are increasing efficacy data about the use of adjustable slings, and long
      term follow-up results are now available for the AdVanceXP male sling. Evidence
      addressing the use of the quadratic Virtue male sling needs further evaluation.
      To date, there is no randomized controlled trial investigating the outcome of one
      specific surgical treatment or comparing the outcome of different surgical
      treatment options. Limitations include the nonsystematic approach. CONCLUSIONS:
      Level of evidence addressing the surgical management of PPI is increasing but
      still unsatisfying. PATIENT SUMMARY: In this review article, we look at current
      research regarding surgical management of stress urinary incontinence following
      radical prostatectomy. Many studies focus on how to predict treatment failure and
      outcomes after artificial urinary sphincter implantation. In addition, more
      information on the long-term results after male sling implantation is now
      available.

PMID- 29174612
TI  - Mortality and its determinants in antiretroviral treatment-naive HIV-infected
      children with suspected tuberculosis: an observational cohort study.
AB  - BACKGROUND: Tuberculosis is a major cause of morbidity and mortality in HIV
      infected children, but is difficult to diagnose. We studied mortality and its
      determinants in antiretroviral treatment (ART)-naive HIV-infected children
      presenting with suspected tuberculosis. METHODS: In this observational cohort
      study, HIV-infected children aged 13 years or younger with suspected tuberculosis
      were followed up for 6 months as part of the ANRS 12229 PAANTHER 01 cohort in
      eight hospitals in four countries (Burkina Faso, Cambodia, Cameroon, and
      Vietnam). Children started ART and antituberculosis treatment at the clinician's
      discretion and were retrospectively classified into one of three groups by
      tuberculosis documentation: confirmed by culture or Xpert MTB/RIF, unconfirmed,
      and unlikely. We assessed mortality and associated factors using Kaplan-Meier
      methods and Cox proportional hazard models. The ANRS 12229 PAANTHER 01 study is
      registered at ClinicalTrials.gov, number NCT01331811. FINDINGS: 266 (61%) of 438
      children enrolled in the study between April 27, 2011, and May 31, 2014, were ART
      naive and included in the analysis (40 had confirmed tuberculosis, 119
      unconfirmed tuberculosis, and 107 unlikely tuberculosis). 112.5 person-years of
      follow-up were available. 154 children (58%) started antituberculosis treatment
      and 212 (80%) started ART. 50 children (19%) died. Mortality by 6 months was
      higher in children with confirmed tuberculosis (14 deaths; 2 month survival
      probability 65.0% [95% CI 50.2-79.8]) compared with unconfirmed tuberculosis (19
      deaths; 83.5% [76.8-90.3]) and unlikely tuberculosis (17 deaths; 83.5% [76.3
      90.7]; log-rank p=0.0141) and was lower in children with confirmed or unconfirmed
      tuberculosis who started antituberculosis treatment (p<0.0001 for both). In a
      multivariate analysis, ART started during the first month of follow-up (hazard
      ratio 0.08; 95% CI 0.01-0.67), confirmed tuberculosis (6.33; 2.15-18.64), young
      age (5.90; 2.02-17.19), CD4 less than 10% (2.63; 1.25-5.53), miliary features
      (4.08; 1.56-10.66), and elevated serum transaminases (4.40; 1.82-10.65) were all
      independently associated with mortality. INTERPRETATION: In our cohort, mortality
      was high in the first 6 months after suspicion of tuberculosis in ART-naive
      children. ART should be started early, particularly in children with factors
      associated with high mortality. Documented or empirical tuberculosis treatment
      decision should be accelerated to reduce mortality and allow early ART
      initiation. FUNDING: ANRS and Fondation Total.

PMID- 29174617
TI  - miR-302/367-induced neurons reduce behavioral impairment in an experimental model
      of Alzheimer's disease.
AB  - In vivo reprogramming of reactive glial cells to neurons has opened a new horizon
      in regenerative medicine. Our previous study showed that astrocytes could be
      converted to neurons by the microRNA-302/367 (miR-302/367) cluster in adult
      brains. In this study, we investigated the possible contribution of miR-302/367
      induced neurons in behavioral improvement and neural repair in an Alzheimer's
      disease (AD) animal model. The AD model was induced by an intracerebroventricular
      (i.c.v) injection of streptozotocin (STZ). GFP-only or miR-302/367+GFP expressing
      lentiviral particles were injected into the dentate gyrus of the hippocampus
      along with intraperitoneal (i.p) valproate (VPA) injection, 3weeks after the STZ
      administration. We assessed short-term and spatial memories by the Y-maze and
      Morris water maze (MWM) tasks, respectively. Electrophysiological activities of
      induced neuron-like cells were investigated using a whole-cell patch clamp
      technique, 6months after injection of miR-302/367. Behavioral analysis showed
      that the STZ injection significantly impaired short-term memory and increased
      escape latency parameter in the MWM task. Compared to STZ and STZ+VPA groups, miR
      302/367 combined with VPA significantly improved the spontaneous alternation and
      spatial memory. Immunostaining against NeuN, as a mature neuronal marker, and its
      quantification indicated that co-labeled GFP and NeuN significantly increased in
      the miR-302/367+VPA group. Induced neurons were detected 6months after the miR
      302/367 injection. The patch-clamp recording suggested that induced neurons could
      fire repetitive action potential like endogenous neurons. In conclusion, our
      results indicated that in vivo reprogramming of reactive astrocytes to neurons by
      the miR-302/367 cluster might be considered as a novel strategy to restore
      learning and memory in AD patients.

PMID- 29174618
TI  - A Randomized Trial of Endovascular Embolization Treatment in Pelvic Congestion
      Syndrome: Fibered Platinum Coils versus Vascular Plugs with 1-Year Clinical
      Outcomes.
AB  - PURPOSE: To compare safety and efficacy of vascular plugs (VPs) and fibered
      platinum coils (FPCs) for embolization in pelvic congestion syndrome (PCS).
      MATERIALS AND METHODS: A randomized, prospective, single-center study enrolled
      100 women with PCS from January 2014 to January 2015. Patients were randomly
      assigned to 2 groups, and embolization was performed with FPCs (n = 50) or VPs (n
      = 50). Mean age of patients was 42.7 years +/- 7.60, and mean visual analog scale
      (VAS) score for pelvic pain before treatment was 7.4 +/- 7.60. Primary outcome
      (clinical success at 1 y using a VAS), number of devices, procedure and
      fluoroscopy times, radiation doses, costs, and complications were compared, and
      participants were followed at 1, 3, 6, and 12 months. RESULTS: Clinical success
      and subjective improvement were not significantly different at 1-year follow-up
      (89.7% for FPCs vs 90.6% for VPs; P = .760). Mean number of devices per case was
      18.2 +/- 1.33 for FPCs and 4.1 +/- 0.31 for VPs (P < .001). Three FPCs and 1 VP
      migrated to pulmonary vasculature approximately 3-6 months after the embolization
      procedure; all were retrieved without complications. The FPC group had a
      significantly longer fluoroscopy time (33.4 min +/- 4.68 vs 19.5 min +/- 6.14)
      and larger radiation dose (air kerma 948.0 mGy +/- 248.45 vs 320.7 mGy +/-
      134.33) (all P < .001). CONCLUSIONS: Embolization for PCS resulted in pain relief
      in 90% of patients; clinical success was not affected by embolic device. VPs were
      associated with decreased fluoroscopy time and radiation dose.

PMID- 29174619
TI  - An elemental approach to modelling the mechanics of the cochlea.
AB  - The motion along the basilar membrane in the cochlea is due to the interaction
      between the micromechanical behaviour of the organ of Corti and the fluid
      movement in the scalae. By dividing the length of the cochlea into a finite
      number of elements and assuming a given radial distribution of the basilar
      membrane motion for each element, a set of equations can be separately derived
      for the micromechanics and for the fluid coupling. These equations can then be
      combined, using matrix methods, to give the fully coupled response. This
      elemental approach reduces to the classical transmission line model if the
      micromechanics are assumed to be locally-reacting and the fluid coupling is
      assumed to be entirely one-dimensional, but is also valid without these
      assumptions. The elemental model is most easily formulated in the frequency
      domain, assuming quasi-linear behaviour, but a time domain formulation, using
      state space method, can readily incorporate local nonlinearities in the
      micromechanics. Examples of programs are included for the elemental model of a
      human cochlea that can be readily modified for other species.

PMID- 29174620
TI  - Numerical study of temperature effects on the poro-viscoelastic behavior of
      articular cartilage.
AB  - This paper presents a new approach to study the effects of temperature on the
      poro- elastic and viscoelastic behavior of articular cartilage. Biphasic solid
      fluid mixture theory is applied to study the poro-mechanical behavior of
      articular cartilage in a fully saturated state. The balance of linear momentum,
      mass, and energy are considered to describe deformation of the solid skeleton,
      pore fluid pressure, and temperature distribution in the mixture. The mechanical
      model assumes both linear elastic and viscoelastic isotropic materials,
      infinitesimal strain theory, and a time-dependent response. The influence of
      temperature on the mixture behavior is modeled through temperature dependent mass
      density and volumetric thermal strain. The fluid flow through the porous medium
      is described by the Darcy's law. The stress-strain relation for time-dependent
      viscoelastic deformation in the solid skeleton is described using the generalized
      Maxwell model. A verification example is presented to illustrate accuracy and
      efficiency of the developed finite element model. The influence of temperature is
      studied through examining the behavior of articular cartilage for confined and
      unconfined boundary conditions. Furthermore, articular cartilage under partial
      loading condition is modeled to investigate the deformation, pore fluid pressure,
      and temperature dissipation processes. The results suggest significant impacts of
      temperature on both poro- elastic and viscoelastic behavior of articular
      cartilage.

PMID- 29174621
TI  - Re: Russel et al: Minimally Invasive Inguinal Lymphadenectomy in the Management
      of Penile Carcinoma (Urology 2017;106:113-118).

PMID- 29174622
TI  - Reply by the Authors.

PMID- 29174623
TI  - Conservatively Managed Peyronie's Disease-Long-term Survey Results From Patients
      Undergoing Nonsurgical and Noninjection Therapies.
AB  - OBJECTIVE: To evaluate patient-reported temporal changes in penile curvature,
      pain, shortening, sexual function, and quality of life in men undergoing
      conservative treatment for PD. MATERIALS AND METHODS: Of 3840 patients who
      underwent evaluation at our institution between 1990 and 2012, 719 were randomly
      selected to receive a mail-in questionnaire with topics including penile
      curvature, pain, shortening, sexual function, and quality of life. Men endorsing
      prior intralesional or surgical therapy were excluded. RESULTS: A total of 125
      patients completed the survey and met the inclusion criteria. The median duration
      between onset of PD symptoms and survey completion was 8.4 years. Overall, 38%
      felt that their condition had overall improved and 26% felt that their condition
      had worsened since onset. Penile curvature resolved in 43%, remained stable in
      37%, and worsened in 20%. Twelve percent of the men developed a second de novo
      curvature. Penile pain occurred in 42%, among whom the pain worsened in 18% and
      completely resolved in 64%. Sixty-five percent reported penile shortening.
      Subjective erectile function decreased in 60%, and >40% experienced difficulties
      with penetrative intercourse. Sexual frequency decreased in 68% of the patients
      and 59% reported decreased relationship satisfaction. Approximately 50% described
      negative psychological impacts on self-esteem and image. CONCLUSION: The current
      report provides the most comprehensive and longest-term data on patient-reported
      outcomes in men undergoing nonsurgical and noninjection therapies. Although
      approximately 40% of the men reported overall and curvature improvement at a
      median 8.4-year follow-up, penile length loss, worsening sexual function,
      relationship dissatisfaction, and psychosocial distress occurred in the majority
      of PD men.

PMID- 29174624
TI  - Clinical Utility of Routine Follow-up Cystography in the Management of Traumatic
      Bladder Ruptures.
AB  - OBJECTIVE: To evaluate if follow-up cystography alters clinical management in
      patients after treatment of traumatic bladder ruptures. METHODS: Patients with
      uncomplicated blunt trauma bladder ruptures between 2000 and 2014 were identified
      in our institutional trauma registry. Primary management strategies consisted of
      either cystorrhaphy or catheter drainage. Primary outcome analyzed was occurrence
      of positive follow-up cystogram. Secondary outcomes were use of follow-up
      cystography and time to negative cystogram. RESULTS: One hundred forty patients
      were identified with a median follow-up of 6.2 months (interquartile range [IQR]
      3.0-32.4). Eighty-two patients (58.6%) had extraperitoneal (EP) ruptures, 49 had
      intraperitoneal (IP) ruptures (35.0%), and 9 had combined EP/IP rupture (6.4%).
      Fifty-six EP patients were managed with catheter drainage, whereas all other
      patients underwent cystorrhaphy. Thirty-five cystorrhaphy patients (42%) had no
      imaging before catheter removal. Forty-nine patients (58%) had cystograms at a
      median of 15.0 days (IQR 10.0-22.0) after cystorrhaphy, with only 1 patient
      having a persistent leak. Forty-six catheter drainage EP patients (82%) had
      negative cystograms at a median of 19.0 days (IQR 15.0-33.0). Of the 10 patients
      with persistent extravasation, 7 required operations for related complications,
      whereas 3 had negative imaging at a median of 38.0 days (IQR 25.8-66.8), with a
      mean of 2.8 cystograms before a negative study. CONCLUSION: Follow-up cystography
      after cystorrhaphy for uncomplicated blunt trauma-associated bladder ruptures
      rarely, if ever, provides unanticipated clinical information. For catheter
      drainage EP patients, cystography remains clinically valuable, as at least 18% of
      patients will have signs of continued extravasation. The optimal timing of
      cystography and catheter removal remains unknown.

PMID- 29174625
TI  - Congenital Stenosis of the External Orifice of the Urethra in a Female Child.
AB  - Limited numbers of pediatric stenosis of the external orifice of the urethra have
      been reported. We report a case of congenital stenosis of the external orifice of
      the urethra in a female child who underwent meatoplasty. As an initial strategy
      for congenital stenosis of the external orifice of the urethra in girls,
      dilatation of the stenosed urethral meatus may be another management of choice.

PMID- 29174626
TI  - [Impact of interventions in the pressure ulcer rate].
AB  - OBJECTIVE: To evaluate the impact of a risk management program for prevention of
      pressure ulcers (PUs) in an adult Intensive Care Unit (ICU). MATERIAL AND
      METHODS: A quantitative, prospective study performed with a "before and after"
      evaluation, and designed in three stages: 1) PU incidence study; 2) Intervention
      by implementing a risk management program, and 3) Assessment of the impact.
      RESULTS: Adherence to the preventive measures showed a significant increase
      (11.7%) between the first month of the program and the final month (58.5%) of the
      assessment. Initial PU rate was 20.9, with a decrease in the rate to 14.0 per
      1000 bed occupancy days (P<.05) after the risk management program. CONCLUSIONS:
      The data show that the risk management program, using prevention measures, was
      effective in reducing the rate of PU in the period under study by more than 33%.

PMID- 29174627
TI  - Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers
      of ketamine.
AB  - We investigated the rapid and sustained antidepressant effects of enantiomers of
      ketamine in N-methyl-d-aspartate (NMDA) receptor GluN2D subunit knockout (GluN2D
      KO) mice. Intraperitoneal administration of ketamine or its enantiomers 10 min
      before the tail-suspension test exerted significant antidepressant effects on
      restraint stress-induced depression in both wildtype and GluN2D-KO mice. The
      antidepressant effects of (RS)-ketamine and (S)-ketamine were sustained 96 h
      after the injection in both wildtype and GluN2D-KO mice, but such sustained
      antidepressant effects of (R)-ketamine were only observed in wildtype mice. These
      data suggest that the GluN2D subunit is critical for the sustained antidepressant
      effects of (R)-ketamine.

PMID- 29174628
TI  - Overexpression of MUC13, a Poor Prognostic Predictor, Promotes Cell Growth by
      Activating Wnt Signaling in Hepatocellular Carcinoma.
AB  - Recently RNA sequencing revealed high mucin 13 (MUC13) expression in
      hepatocellular carcinoma (HCC) tissues. To understand the clinicopathologic
      significance of MUC13 in HCC, quantitative PCR and immunohistochemistry were used
      to detect its expression in paired tumor tissues and nontumor tissues. The
      oncoprotein role of MUC13 was determined by in vitro and in vivo assays.
      Overexpression of MUC13 was detected in 74 of 168 primary HCC cases (44%) and was
      significantly associated with tumor size (P = 0.027), stage (P = 0.006),
      encapsulation (P = 0.044), venous invasion (P = 0.024), and poor outcome (P =
      0.004). Functional studies demonstrated MUC13 had strong oncogenic activity by
      promoting cell growth, colony formation, cell migration, and tumor formation in
      nude mice. The pro-oncogenic effect of MUC13 were effectively inhibited by RNA
      interference. MUC13 promoted cellular G1/S phase transition by activating Wnt
      signaling. Mechanistically, MUC13 bound to beta-catenin and increased its
      phosphorylation at Ser552 and Ser675 sites, which subsequently promoted nuclear
      translocation of beta-catenin and up-regulation of its downstream target genes
      Axin2, c-Myc, and CyclinD1. Knockdown of AKT with shRNA in MUC13-overexpressing
      cells nullified the elevated phosphorylation of beta-catenin by MUC13. In
      clinical HCC samples, nuclear translocation of beta-catenin was significantly
      associated with MUC13 overexpression (P = 0.001). Overexpression of MUC13 plays a
      critical role in the development and progression of HCC by activating Wnt
      signaling.

PMID- 29174629
TI  - Effect of transformational leadership on job satisfaction and patient safety
      outcomes.
AB  - BACKGROUND: Improving patient safety within health care organizations requires
      effective leadership at all levels. PURPOSE: The objective of this study was to
      investigate the effects of nurse managers' transformational leadership behaviors
      on job satisfaction and patient safety outcomes. METHODS: A random sample of
      acute care nurses in Ontario (N = 378) completed the crosssectional survey.
      Hypothesized model was tested using structural equation modeling. FINDING: The
      model fit the data acceptably. Transformational leadership had a strong positive
      influence on workplace empowerment, which in turn increased nurses' job
      satisfaction and decreased the frequency of adverse patient outcomes.
      Subsequently, job satisfaction was related to lower adverse events. CONCLUSION:
      The findings provide support for managers' use of transformational leadership
      behaviors as a useful strategy in creating workplace conditions that promote
      better safety outcomes for patients and nurses.

PMID- 29174630
TI  - Is the adjustable transobturator system ATOMS(r) useful for the treatment of male
      urinary incontinence in low to medium volume urological centers?
AB  - INTRODUCTION: Urinary incontinence (UI) is a complication of radical
      prostatectomy (RP) and transurethral resection of the prostate (TURP). The gold
      standard treatment is the artificial urinary sphincter, however, new treatments
      have been investigated. OBJECTIVE: To examine the outcome of an adjustable
      transobturator male system (ATOMS(r)) in men with UI after prostatic surgery in a
      low to medium volume continence center. MATERIALS AND METHODS: Twenty-five men
      with UI were implanted with ATOMS(r) system between 2012 and 2014. The most
      common indication was UI after RP (92%), followed by UI after TURP (8%). Eleven
      patients (44%) had received adjuvant external beam radiotherapy (RT). Patients
      were considered to be 'dry' if they stopped wearing pads or needed just one
      protective pad per day; and improved if the daily number of pads used decreased
      by at least half. The Incontinence Quality of Life questionnaire (ICIQ-SF) was
      used, adding a verbal question about the satisfaction of the patient considering
      the outcome. RESULTS: After a mean follow-up of 21.56 months, 64% were dry and 8%
      revealed a significant improvement. The success of the procedure was negatively
      correlated with the severity of the previous UI and with previous treatment with
      RT. Concerning patients satisfaction, 84% of the patients would repeat the
      procedure. CONCLUSION: ATOMS(r) offers good rates of cure and improvement of UI
      after prostatic surgery with a reasonable rate of minor complications. The
      results of this study, performed in a low to medium volume continence center, are
      comparable to the results achieved in high volume continence centers.

PMID- 29174631
TI  - Corrigendum to "X-linked elliptocytosis with impaired growth is related to
      mutated AMMECR1" [Gene 606C (2017) 47-52].

PMID- 29174632
TI  - Recent cancer treatment and memory decline in older adults: An analysis of the
      2002-2012 Health and Retirement Study.
AB  - OBJECTIVE: Few studies have examined the impact of cancer treatment on cognitive
      trajectories in the growing population of older adults diagnosed with and
      surviving cancer. This study examined whether recent cancer and its treatment
      accelerated memory decline in older adults. MATERIALS AND METHODS: We conducted a
      secondary analysis of observations drawn from the Health and Retirement Study
      (2002-2012), a population-based sample of older adults in the United States.
      Changes in immediate (IWR) and delayed word recall (DWR) scores were estimated by
      latent growth modeling in individuals who never had cancer (n=10,939) or had been
      diagnosed with cancer between 2000 and 2002 and received treatment with some
      combination of radiation and/or surgery (n=240), chemotherapy only (n=34), or
      chemotherapy and some combination of radiation and/or surgery (n=64). RESULTS: In
      the period immediately following treatment, individuals reporting a recent cancer
      treated with chemotherapy and surgery/radiation experienced significantly more
      rapid decline in IWR (b =-0.34, SE =0.17, p=0.047) and DWR (b=-0.38, SE=0.19,
      p=0.049) than the non-cancer group. Sensitivity analyses addressing mortality
      selection and memory-related disease at baseline attenuated the strength of these
      associations. There were no other statistically significant differences in
      estimated linear or quadratic slope by cancer status or treatment. CONCLUSION:
      Our results support a potential association between recent cancer treatment and
      trajectories of memory decline in older adults and provide guidance on the
      interpretation of statistical estimates from panel studies of health and aging.

PMID- 29174633
TI  - Regulation of innate immune functions by guanylate-binding proteins.
AB  - Guanylate-binding proteins (GBP) are a family of dynamin-related large GTPases
      which are expressed in response to interferons and other pro-inflammatory
      cytokines. GBPs mediate a broad spectrum of innate immune functions against
      intracellular pathogens ranging from viruses to bacteria and protozoa. Several
      binding partners for individual GBPs have been identified and several different
      mechanisms of action have been proposed depending on the organisms, the cell type
      and the pathogen used. Many of these anti-pathogenic functions of GBPs involve
      the recruitment to and the subsequent destruction of pathogen containing vacuolar
      compartments, the assembly of large oligomeric innate immune complexes such as
      the inflammasome, or the induction of autophagy. Furthermore, GBPs often
      cooperate with immunity-related GTPases (IRGs), another family of dynamin-related
      GTPases, to exert their anti-pathogenic function, but since most IRGs have been
      lost in the evolution of higher primates, the anti-pathogenic function of human
      GBPs seems to be IRG-independent. GBPs and IRGs share biochemical and structural
      properties with the other members of the dynamin superfamily such as low
      nucleotide affinity and a high intrinsic GTPase activity which can be further
      enhanced by oligomerisation. Furthermore, GBPs and IRGs can interact with lipid
      membranes. In the case of three human and murine GBP isoforms this interaction is
      mediated by C-terminal isoprenylation. Based on cell biological studies, and in
      analogy to the function of other dynamins in membrane scission events, it has
      been postulated that both GBPs and IRGs might actively disrupt the outer membrane
      of pathogen-containing vacuole leading to the detection and destruction of the
      pathogen by the cytosolic innate immune system of the host. Recent evidence,
      however, indicates that GBPs might rather function by mediating membrane
      tethering events similar to the dynamin-related atlastin and mitofusin proteins,
      which mediate fusion of the ER and mitochondria, respectively. The aim of this
      review is to highlight the current knowledge on the function of GBPs in innate
      immunity and to combine it with the recent progress in the biochemical
      characterisation of this protein family.

PMID- 29174634
TI  - A parametric interpretation of Bayesian Nonparametric Inference from Gene
      Genealogies: Linking ecological, population genetics and evolutionary processes.
AB  - Using a nonparametric Bayesian approach Palacios and Minin (2013) dramatically
      improved the accuracy, precision of Bayesian inference of population size
      trajectories from gene genealogies. These authors proposed an extension of a
      Gaussian Process (GP) nonparametric inferential method for the intensity function
      of non-homogeneous Poisson processes. They found that not only the statistical
      properties of the estimators were improved with their method, but also, that key
      aspects of the demographic histories were recovered. The authors' work represents
      the first Bayesian nonparametric solution to this inferential problem because
      they specify a convenient prior belief without a particular functional form on
      the population trajectory. Their approach works so well and provides such a
      profound understanding of the biological process, that the question arises as to
      how truly "biology-free" their approach really is. Using well-known concepts of
      stochastic population dynamics, here I demonstrate that in fact, Palacios and
      Minin's GP model can be cast as a parametric population growth model with density
      dependence and environmental stochasticity. Making this link between population
      genetics and stochastic population dynamics modeling provides novel insights into
      eliciting biologically meaningful priors for the trajectory of the effective
      population size. The results presented here also bring novel understanding of GP
      as models for the evolution of a trait. Thus, the ecological principles
      foundation of Palacios and Minin (2013)'s prior adds to the conceptual and
      scientific value of these authors' inferential approach. I conclude this note by
      listing a series of insights brought about by this connection with Ecology.

PMID- 29174635
TI  - The independent loss model with ordered insertions for the evolution of CRISPR
      spacers.
AB  - Today, the CRISPR (clustered regularly interspaced short palindromic repeats)
      region within bacterial and archaeal genomes is known to encode an adaptive
      immune system. We rely on previous results on the evolution of the CRISPR arrays,
      which led to the ordered independent loss model, introduced by Kupczok and
      Bollback (2013). When focusing on the spacers (between the repeats), new elements
      enter a CRISPR array at rate theta at the leader end of the array, while all
      spacers present are lost at rate rho along the phylogeny relating the sample.
      Within this model, we compute the distribution of distances of spacers which are
      present in all arrays in a sample of size n. We use these results to estimate the
      loss rate rho from spacer array data for n=2 and n=3.

PMID- 29174636
TI  - Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer:
      Methodological issues.

PMID- 29174637
TI  - Apolipoprotein E4 exacerbates ethanol-induced neurotoxicity through augmentation
      of oxidative stress and apoptosis in N2a-APP cells.
AB  - Neuronal loss is a prominent phenomenon in Alzheimer's disease (AD) and alcohol
      induced brain damage. Alcohol abuse is associated with an increased risk of AD,
      regardless of the type of alcoholic beverage. Furthermore, the detrimental effect
      of excessive alcohol consumption on the risk of AD is exacerbated among people
      carrying apolipoprotein E (APOE) epsilon4 allele, the major genetic risk factor
      for AD. However, how APOE epsilon4 and alcohol abuse synergistically enhance the
      possibility of AD is unclear. Here we show that in N2a cells stably expressing
      human APP695 (N2a-APP), high-concentration ethanol-induced neurotoxicity was
      significantly augmented in the presence of apoE4 protein, compared with apoE3
      protein. Early and late apoptotic cells were apparently more in cells treated
      with the combination of apoE4 and ethanol, compared with that of apoE3 and
      ethanol. Inhibition of apoptosis using a pan-caspase inhibitor z-vad resulted in
      abolishment of the apoE isoform-specific effect on high-concentration ethanol
      induced neurotoxicity. Moreover, compared with apoE3, apoE4 augmented ethanol
      induced cellular oxidative stress, and pre-incubation with a reactive oxygen
      species (ROS) scavenger NAC abrogated the specific effect of apoE4 on ethanol
      induced neurotoxicity. Taken together, our results for the first time demonstrate
      that apoE4 and high-concentration ethanol synergistically enhance neurotoxicity
      through elevating cellular oxidative stress and increasing neuronal apoptosis,
      and support the notion that avoiding excessive alcohol consumption can help to
      prevent AD especially in APOE epsilon4 carriers.

PMID- 29174638
TI  - Upregulation of CCL7 and CCL2 in reward system mediated through dopamine D1
      receptor signaling underlies methamphetamine-induced place preference in mice.
AB  - We previously showed that the CC-chemokine ligand 2 (CCL2)-CC-chemokine receptor
      2 (CCR2) system is responsible for conditioned place preference (CPP) by
      methamphetamine (Meth). In this study, we investigated the roles for other
      chemokines mediating Meth-induced CPP and the upstream factors upregulating
      chemokines in mice. We found that CCL7 mRNA level was upregulated in the
      prefrontal cortex (PFC) after Meth administration (3mg/kg, subcutaneous), and
      increased CCL7 immunoreactivity was localized to the PFC NeuN-positive neurons.
      Meth-induced CPP was blocked by the dopamine D1 receptor antagonist SCH 23390 but
      not by the D2 receptor antagonists raclopride or haloperidol. The D1 receptor
      agonist SKF 81297 alone elicited CPP, suggesting a critical role of D1 receptor
      signaling in Meth-induced reward. Consistent with these results, the Meth-induced
      upregulation of CCL7 and CCL2 were attenuated by SCH 23390, and a single
      administration of SKF 81297 upregulated mRNA expression levels of CCL7 and CCL2
      in the PFC. Furthermore, Meth-induced CPP was prevented by INCB 3284, a selective
      antagonist of CCR2, a receptor that binds both CCL7 and CCL2. Collectively, we
      identified two CC-chemokines (i.e., CCL7 and CCL2) as key regulatory factors in
      Meth-induced reward. Pharmacological inhibitors of these chemokines may warrant
      development as novel therapeutics for ameliorating Meth addiction.

PMID- 29174639
TI  - Callosotomy affects performance IQ: A meta-analysis of individual participant
      data.
AB  - Morphometric neuroimaging studies on healthy adult individuals regularly report a
      positive association between intelligence test performance (IQ) and structural
      properties of the corpus callosum (CC). At the same time, studies examining the
      effect of callosotomy on epilepsy patients report only negligible changes in IQ
      as result of the surgery, partially contradicting the findings of the morphometry
      studies. Objective of the present meta-analysis of individual participant data
      (IPD) of 87 cases from 16 reports was to re-investigate the effect of callosotomy
      on full scale IQ as well as on the verbal and performance subscale under special
      consideration of two possible moderating factors: pre-surgical IQ levels and the
      extent of the surgery (complete vs. anterior transsection). The main finding was
      that callosotomy selectively affects performance IQ, whereby the effect is
      modulated by the pre-surgical level of performance. Patients with an above-median
      pre-surgery performance IQ level show a significant average decrease of -5.44
      (CI95%: - 8.33 to - 2.56) IQ points following the surgery, while the below-median
      group does not reveal a significant change in IQ (mean change: 1.01 IQ points;
      CI95%: -1.83 to 3.86). Thus, the present analyses support the notion that
      callosotomy has a negative effect on the patients' performance IQ, but only in
      those patients, who at least have an average performance levels before the
      surgery. This observation also lends support to the findings of previous
      morphometry studies, indicating that the frequently observed CC-IQ correlation
      might indeed reflect a functional contribution of callosal interhemispheric
      connectivity to intelligence-test performance.

PMID- 29174640
TI  - Dorsal raphe nucleus glucocorticoid receptors inhibit tph2 gene expression in
      male C57BL/6J mice.
AB  - The serotonergic dorsal raphe nucleus (DRN) expresses glucocorticoid receptors
      (GR), and systemic glucocorticoids have been shown to regulate expression and
      activity of tryptophan hydroxylase isoform 2, the rate-limiting enzyme for
      serotonin synthesis in brain. We have used intra-DRN injection of pseudotyped
      adeno-associated virus AAV2/9 transducing either green fluorescent protein (GFP
      control) or Cre recombinase (DRN GR deletion) in floxed GR mice to determine if
      DRN GR directly regulate DRN mRNA levels of tryptophan hydroxylase 2 (tph2). In a
      separate set of similarly-treated floxed GR mice, we also measured limbic
      forebrain region concentrations of serotonin (5-hydroxytryptamine; 5-HT) and its
      major metabolite, 5-hydroxyindoleacetic acid (5-HIAA). DRN GR deletion increased
      tph2 mRNA levels in the dorsal, lateral wing, and caudal parts of the DRN without
      altering tissue concentrations of 5-HT, 5-HIAA, or the 5-HIAA/5-HT ratio in
      limbic forebrain regions. We conclude that DRN GR inhibit DRN tph2 gene
      expression in mice without marked effects on serotonin metabolism, at least under
      basal conditions at the circadian nadir. These data provide the first evidence of
      localized control of DRN tph2 mRNA expression by DRN GR in mice.

PMID- 29174642
TI  - Source data supported high resolution carbon emissions inventory for urban areas
      of the Beijing-Tianjin-Hebei region: Spatial patterns, decomposition and policy
      implications.
AB  - This paper developed internationally compatible methods for delineating
      boundaries of urban areas in China. By integrating emission source data with
      existing official statistics as well as using rescaling methodology of data
      mapping for 1 km grid, the authors constructed high resolution emission gridded
      data in Beijing-Tianjin-Hebei (Jing-Jin-Ji) region in China for 2012. Comparisons
      between urban and non-urban areas of carbon emissions from industry, agriculture,
      household and transport exhibited regional disparities as well as sectoral
      differences. Except for the Hebei province, per capita total direct carbon
      emissions from urban extents in Beijing and Tianjin were both lower than
      provincial averages, indicating the climate benefit of urbanization, comparable
      to results from developed countries. Urban extents in the Hebei province were
      mainly industrial centers while those in Beijing and Tianjin were more service
      oriented. Further decomposition analysis revealed population to be a common major
      driver for increased carbon emissions but climate implications of urban design,
      economic productivity of land use, and carbon intensity of GDP were both cluster-
      and sector-specific. This study disapproves the one-size-fits-all solution for
      carbon mitigation but calls for down-scaled analysis of carbon emissions and
      formulation of localized carbon reduction strategies in the Jing-Jin-Ji as well
      as other regions in China.

PMID- 29174641
TI  - Effects of sequential ethanol exposure and repeated high-dose methamphetamine on
      striatal and hippocampal dopamine, serotonin and glutamate tissue content in
      Wistar rats.
AB  - Alcohol (ethanol) and methamphetamine (METH) co-abuse is a major public health
      issue. Ethanol or METH exposure has been associated with changes in
      neurotransmitter levels in several central brain regions. However, little is
      known about the effect of sequential exposure to ethanol and METH on glutamate,
      dopamine and serotonin tissue content in striatum and hippocampus. In this study,
      we investigated the effects of sequential exposure to ethanol and METH on tissue
      content of these neurotransmitters. Male Wistar rats were orally gavaged with
      either ethanol (6g/kg) or water for seven days. Rats were administered with high
      dose of METH (10mg/kg, i.p. every 2h*4) or saline on Day 8 and euthanized 48h of
      last METH or saline i.p. injection. In the striatum, sequential exposure to
      ethanol and METH increased glutamate tissue content while reducing dopamine and
      serotonin tissue content as compared to the group exposed to ethanol alone. In
      the hippocampus, sequential exposure to ethanol and METH decreased serotonin
      tissue content as compared to the group that was exposed to ethanol alone.
      However, this study showed that ethanol has no additive effect to METH on tissue
      content of dopamine and serotonin as compared to METH in the striatum and
      hippocampus. This study demonstrated that sequential exposure of ethanol and METH
      has an additive effect on tissue content of certain neurotransmitters in the
      brain.

PMID- 29174643
TI  - Inactivation of Bacillus anthracis spores to decontaminate subway railcar and
      related materials via the fogging of peracetic acid and hydrogen peroxide
      sporicidal liquids.
AB  - The inactivation of Bacillus anthracis spores on subway and used subway railcar
      materials was evaluated using fogged peracetic acid/hydrogen peroxide (PAA) and
      hydrogen peroxide (H2O2). A total of 21 separate decontamination tests were
      conducted using bacterial spores of both B. anthracis Ames (B.a.) and Bacillus
      atrophaeus (B.g.) inoculated onto several types of materials. Tests were
      conducted using commercial off-the-shelf fogging equipment filled with either PAA
      or H2O2 to fumigate a ~15 cubic meter chamber under uncontrolled ambient relative
      humidity and controlled temperature (10 or 20  degrees C) from 8 to 168 h. For
      the present study, no conditions were found that resulted in complete
      inactivation of either B.a. Ames or B.g. on all test materials. Approximately 41%
      and 38% of the decontamination efficacies for B.a. and B.g., respectively,
      exhibited >=6 log10 reduction (LR); efficacy depended greatly on the material.
      When testing at 10  degrees C, the mean LR was consistently lower for both B.a.
      and B.g. as compared to 20  degrees C. Based on the statistical comparison of the
      LR results, B.g. exhibited equivalent or greater resistance than B.a. for
      approximately 92% of the time across all 21 tests. The efficacy data suggest that
      B.g. may be a suitable surrogate for B.a. Ames when assessing the decontamination
      efficacy of fogged PAA or H2O2. Moreover, the results of this testing indicate
      that in the event of B.a. spore release into a subway system, the fogging of PAA
      or H2O2 represents a decontamination option for consideration.

PMID- 29174644
TI  - Does the reduction of inferior turbinate affect lower airway functions?
AB  - INTRODUCTION: Although the nose and lungs are separate organs, numerous studies
      have reported that the entire respiratory system can be considered as a single
      anatomical and functional unit. The upper and lower airways affect each other
      either directly or through reflex mechanisms. OBJECTIVE: In this study, we aimed
      to evaluate the effects of the radiofrequency ablation of persistent inferior
      turbinate hypertrophy on nasal and pulmonary function. METHODS: Twenty-seven
      patients with bilateral persistent inferior turbinate hypertrophy without septal
      deviation were included in this study. All of the patients were evaluated using
      anterior rhinoscopy, nasal endoscopy, acoustic rhinometry, a visual analogue
      scale, and flow-sensitive spirometry on the day before and 4 months after the
      radiofrequency ablation procedure. RESULTS: The post-ablation measurements
      revealed that the inferior turbinate ablation caused an increase in the mean
      cross-sectional area and volume of the nose, as well as in the forced expiratory
      volume in 1s, forced vital capacity, and peak expiratory flow of the patients.
      These differences between the pre- and post-ablation results were statistically
      significant. The post-ablation visual analogue scale scores were lower when
      compared with the pre-ablation scores, and this difference was also statistically
      significant. CONCLUSION: This study demonstrated that the widening of the nasal
      passage after the reduction of the inferior turbinate size had a favorable effect
      on the pulmonary function tests.

PMID- 29174645
TI  - The attitudes of emergency department nurses towards patient safety.
AB  - This research was planned to identify the attitudes of emergency department
      nurses towards patient safety. The study was performed as descriptive. The
      universe of the research the universe comprised hospitals defined as 3rd level
      according to Turkish health care classification, which provides service to all
      health disciplines in Istanbul. The sample consisted of emergency department (ED)
      nurses who work in those hospitals. The data was collected by using tools such as
      the "Information Questionnaire" and the "Patient Safety Attitudes Scale". In this
      study, the attitudes of ED nurses towards patient safety were found to be average
      and was not related to age, gender, education level, nursing experience, ED
      experience, ED certification, patient safety training, nurse's self sufficiency
      perception of patient safety, hospital's quality certification or ED quality
      certification. The attitudes of nurses towards patient safety were compared by
      age, gender, marital status, education level, ED experience and there was no
      meaningful difference. However, a meaningful difference was found between the age
      groups and the "defining stress" sub-dimension of the Patient Safety Attitudes
      Scale. ED nurses' status of certification for emergency care, patient safety
      training, training of quality, hospitals' or ED's quality certification status
      had no significant statistical difference.

PMID- 29174646
TI  - Exploring pharmacist experiences of delivering individualised prescribing error
      feedback in an acute hospital setting.

PMID- 29174647
TI  - Stabilization of axisymmetric liquid bridges through vibration-induced pressure
      fields.
AB  - Previous theoretical studies have indicated that liquid bridges close to the
      Plateau-Rayleigh instability limit can be stabilized when the upper supporting
      disk vibrates at a very high frequency and with a very small amplitude. The major
      effect of the vibration-induced pressure field is to straighten the liquid bridge
      free surface to compensate for the deformation caused by gravity. As a
      consequence, the apparent Bond number decreases and the maximum liquid bridge
      length increases. In this paper, we show experimentally that this procedure can
      be used to stabilize millimeter liquid bridges in air under normal gravity
      conditions. The breakup of vibrated liquid bridges is examined experimentally and
      compared with that produced in absence of vibration. In addition, we analyze
      numerically the dynamics of axisymmetric liquid bridges far from the Plateau
      Rayleigh instability limit by solving the Navier-Stokes equations. We calculate
      the eigenfrequencies characterizing the linear oscillation modes of vibrated
      liquid bridges, and determine their stability limits. The breakup process of a
      vibrated liquid bridge at that stability limit is simulated too. We find
      qualitative agreement between the numerical predictions for both the stability
      limits and the breakup process and their experimental counterparts. Finally, we
      show the applicability of our technique to control the amount of liquid
      transferred between two solid surfaces.

PMID- 29174648
TI  - A new three-dimensional zinc-based metal-organic framework as a fluorescent
      sensor for detection of cadmium ion and nitrobenzene.
AB  - In this study, a novel three-dimensional zinc-based metal-organic framework (Zn
      MOF), i.e., {Zn2(L)2(DMF)2H2O}n (L = 2,5-bis(phenylamino)-1,4-benzenedicarboxylic
      acid) was designed and developed under solvothermal condition. As a proof-of
      principle, a pi-conjugated framework of carboxylate ligand capable of "bottom up"
      synthesis was integrated with metal ion to construct a novel MOF for sensing
      applications. As expected, the synthesized Zn-MOF exhibited fluorescence
      enhancement for cadmium ion (Cd2+) and sensing of nitrobenzene (NB) through
      fluorescence quenching. The detection limits were calculated to be 0.12 MUM for
      Cd2+ and 1.19 MUg mL-1 for NB based on signal-to-noise ratio of 3:1. Moreover,
      various techniques and density functional theory investigations verified that the
      possible sensing mechanisms for Cd2+ and NB included ion exchange and
      photoinduced electron transfer, respectively. Finally, their practical
      applications on real samples also demonstrated that the Zn-MOF-based sensor can
      be effectively utilized for detection and imaging of Cd2+ present in the real
      water samples and living cells. This study may inspire future research and design
      of target fluorescent MOFs with specific functions.

PMID- 29174649
TI  - From fly ash waste slurry to functional adsorbent for valuable rare earth ion
      separation: An ingenious combination process involving modification, dewatering
      and grafting.
AB  - Acid extracting aluminum from fly ash would produce pestilent secondary fly ash
      slurry with strong acidity, high content of Cl- and residual Al3+ that is
      difficult to be further used. In order to achieve the zero emission, a potential
      integrated treatment process for reutilization was proposed in this paper. By
      intelligent use of residual Al3+ in sludge as catalyst, hydrophobic modification
      of solid particle was taken with fatty acid via a heterogeneous esterification at
      normal temperature. Due to the solvophobic force, moisture content of its filter
      cake was 36.46%, which reduced 11.14% compared with the unmodified one,
      hydrophobicity scale can achieve 100% with modifier accounting for only 0.8% of
      solid content and the Cl- concentrations decreased from 20 to 0.102 g/L in wash
      liquor, thus greatly saving water for washing and energy for drying.
      Subsequently, based on the appearance of hydrocarbon chains on particle surface,
      a high-efficiency ultraviolet-induced grafting polymerization was implemented to
      fabricate density polyacrylic acid decorated fly ash particles from the surface
      "CH" sites, the resultant composite was proved to efficiently separate valuable
      rare-earth Gd3+ from wastewater with outstanding adsorption and regeneration
      performance, hence bringing high added-value utilization for these hazardous
      waste.

PMID- 29174651
TI  - Cancer combination therapy of the sesquiterpenoid artesunate and the selective
      EGFR-tyrosine kinase inhibitor erlotinib.
AB  - BACKGROUND: The shift from cytotoxic to targeted chemotherapy led to improved
      treatment outcomes in oncology. Nevertheless, many cancer patients cannot be
      cured from their disease because of the development of drug resistance and side
      effects. PURPOSE: There is an ongoing quest for novel compounds, which raised not
      only the interest in natural products but also in novel combination therapy
      regimens. STUDY DESIGN: In this review, we report on the inhibition epidermal
      growth factor receptor (EGFR) by targeted small molecules and their combination
      with natural products from medicinal plants. RESULTS: The combination of
      erlotinib with artesunate leads to synergistic inhibition of cell growth in
      isobologram analyses. Artesunate is an approved anti-malaria drug, which is also
      active against cancer as shown in vitro, in vivo and in preliminary clinical
      phase I/II trials. CONCLUSION: The combination of natural products (e.g. the
      sesquiterpenoid artesunate) and synthetic compounds (e.g. the small molecule EGFR
      tyrosine kinase inhibitor erlotinib) may lead to improved clinical success rates
      in oncology.

PMID- 29174650
TI  - Orphan neuropeptides and receptors: Novel therapeutic targets.
AB  - Neuropeptides are the largest class of intercellular signaling molecules,
      contributing to a wide variety of physiological processes. Neuropeptide receptors
      are therapeutic targets for a broad range of drugs, including medications to
      treat pain, addiction, sleep disorders, and nausea. In addition to >100 peptides
      with known functions, many peptides have been identified in mammalian brain for
      which the cognate receptors have not been identified. Similarly, dozens of
      "orphan" G protein-coupled receptors have been identified in the mammalian
      genome. While it would seem straightforward to match the orphan peptides and
      receptors, this is not always easily accomplished. In this review we focus on
      peptides named PEN and big LEN, which are among the most abundant neuropeptides
      in mouse brain, and their recently identified receptors: GPR83 and GPR171. These
      receptors are co-expressed in some brain regions and are able to interact.
      Because PEN and big LEN are produced from the same precursor protein and co
      secreted, the interaction of GPR83 and GPR171 is physiologically relevant. In
      addition to interactions of these two peptides/receptors, PEN and LEN are co
      localized with neuropeptide Y and Agouti-related peptide in neurons that regulate
      feeding. In this review, using these peptide receptors as an example, we
      highlight the multiple modes of regulation of receptors and present the emerging
      view that neuropeptides function combinatorially to generate a network of
      signaling messages. The complexity of neuropeptides, receptors, and their
      signaling pathways is important to consider both in the initial deorphanization
      of peptides and receptors, and in the subsequent development of therapeutic
      applications.

PMID- 29174652
TI  - Introduction: Novel hybrid combinations containing synthetic or antibiotic drugs
      with plant-derived phenolic or terpenoid compounds.
AB  - BACKGROUND: There is a paradigm shift in chemotherapy from mono-drug therapy
      towards multidrug combination regimens. Natural products from medicinal plants
      may play an important role for the design of novel combination therapy protocols.
      HYPOTHESIS: We introduce the novel term "hybrid combination" for the therapeutic
      combination of chemically defined plant-derived constituents (e.g. phenolic or
      terpenoid compounds with synthetic or antibiotic drugs to increase
      pharmacological activity and simultaneously toxic side effects. STUDY DESIGN:
      Several literature databases were screened on the combination of
      phenolic/terpenoid compounds with synthetic/antibiotic drugs. RESULTS: Phenolic
      compounds are water soluble and interact with target proteins due to their OH
      groups. They reveal antioxident, antiinflammatory and sometimes apoptotic
      activities whereas the terpenoids possess due to their lipophilic nature together
      with the phenolics amphiphilic properties and thereby good cell-penetrating
      features. They reveal antioxidant properties, anti-inflammatory and sometimes
      apoptotic activities as well as cell-penetrating features due to their
      amphiphilicity. Synergistic or antagonistic interactions with synthetic or
      antibiotic drugs have to be demonstrated by using suitable methods (e.g.
      isobologram analysis). The molecular modes of action may be elucidated by
      approaches of network pharmacology (e.g. protein-protein interaction networks).
      CONCLUSION: There is convincing evidence for the improvement of pharmacological
      activity at reduced side effects by hybrid combinations. Future efforts should
      focus on clinical trials with hybrid combinations to treat a broad range of
      diverse diseases such as cardiometabolic and neurotropic syndromes, drug
      resistance phenotypes, and so-called neglected infectious diseases.

PMID- 29174653
TI  - Color-coded LED microscopy for quantitative phase imaging: Implementation and
      application to sperm motility analysis.
AB  - Color-coded light-emitting diode (LED) microscopy (cLEDscope) is a novel
      computational microscopy technique capable of multi-contrast and quantitative
      phase imaging of biological specimens using color-multiplexed illumination. Using
      specially designed LED patterns, it is capable of recording multiple differential
      phase contrast (DPC) images in a single exposure and employs a computational
      algorithm to retrieve the phase distribution of the specimens. Herein, we
      describe the detailed procedures in the cLEDscope implementation for quantitative
      phase imaging. Several notable features and caveats in the cLEDscope setup and
      image processing are also outlined. The imaging model is derived for our specific
      configuration, and the associated phase-retrieval algorithms are presented on the
      basis of a weak-object transfer function. As an illustrative application of the
      quantitative cLEDscope, we demonstrate its utility as a sperm-motility analyzer
      by exploiting its real-time quantitative imaging capability.

PMID- 29174654
TI  - Systems to study codon effect on post-transcriptional regulation of gene
      expression.

PMID- 29174655
TI  - Evaluation of an automated ultraviolet-C light disinfection device and patient
      hand hygiene for reduction of pathogen transfer from interactive touchscreen
      computer kiosks.
AB  - Touchscreens are a potential source of pathogen transmission. In our facility,
      patients and visitors rarely perform hand hygiene after using interactive
      touchscreen computer kiosks. An automated ultraviolet-C touchscreen disinfection
      device was effective in reducing bacteriophage MS2, bacteriophage phiX174,
      methicillin-resistant Staphylococcus aureus, and Clostridium difficile spores
      inoculated onto a touchscreen. In simulations, an automated ultraviolet-C
      touchscreen disinfection device alone or in combination with hand hygiene reduced
      transfer of the viruses from contaminated touchscreens to fingertips.

PMID- 29174656
TI  - Do donated linens put patients at risk for fungal infections during
      hospitalization? A pediatric case investigation and subsequently implemented
      process changes.

PMID- 29174657
TI  - Serious unintended outcomes associated with cesarean section.
AB  - BACKGROUND: Serious unintended outcomes (SUOs) associated with cesarean section
      (CS), defined in this study as sepsis, endometritis, or wound disruption,
      occurring during the admission to deliver an infant by CS, or on readmission for
      wound disruption, are not routinely measured in a manner that continuously
      evaluates their impact on women's health. METHODS: The Texas Healthcare
      Information Collection Public Use Data File was used to investigate trends in the
      diagnosis of SUOs over a 5-year period from January 1, 2010-December 31, 2014.
      RESULTS: CS-associated SUOs affected 9.24 women for every 1,000 CSs. During the
      study period, a large decrease in the rate of SUOs occurred (R2 = 0.60). This was
      potentially influenced by a large decrease in the rate of endometritis (R2 =
      0.41). Decreases in the diagnosis of and readmission for CS wound disruption were
      not as large (R2 = 0.06 and R2 = 0.03, respectively). A large increase in CS
      associated sepsis (R2 = .32) was identified. Administrative coded data used to
      identify SUOs in this study may have utility for the identification of serious
      unintended outcomes associated with CS at the population level. CONCLUSIONS:
      Increases in length of stay and utilization of critical care were noted among
      women affected by CS-associated SUOs. Additional study is needed to determine
      factors that increase the likelihood of the development of SUO and to evaluate
      the preventability of these events.

PMID- 29174658
TI  - [Management of endometrioma].
AB  - Preoperative evaluation: clinical examination, and research for associated
      lesions. Laparoscopic approach. Cystectomy: gold standard, conformed to the
      endometrioma pathophysiology (3 zones). Laser CO2 Plasmajet(r) vaporisation:
      important data lead to legitimate utilisation. Haemostasis: be patient! Use of
      bipolar energy sparingly. Look for other endometriotic lesions, and systematic
      treatment. Preoperative medical treatment not always useful. Postoperative
      treatment: decrease recurrence. Especially for patients with no immediate
      pregnancy desire.

PMID- 29174659
TI  - Impact of a Monoplane Hemodynamic TEE (hTEE) Monitoring Device on Decision Making
      in a Heterogeneous Hemodynamically Unstable Intensive Care Unit Population: A
      Prospective, Observational Study.
AB  - OBJECTIVE: This prospective observational study was undertaken to evaluate the
      utility of a miniature transesophageal echocardiography probe (ImaCor hemodynamic
      [hTEE]) in the management of hemodynamically unstable intensive care unit
      patients with and without various forms of mechanical circulatory support.
      DESIGN: A prospective observational study. SETTING: A single tertiary care
      cardiothoracic and surgical intensive care unit. PARTICIPANTS: Fifty-three
      cardiothoracic and surgical intensive care unit patients undergoing miniature
      transesophageal echocardiography examinations. All patients had hemodynamic
      instability as defined by necessity of mechanical circulatory support (MCS)
      devices or vasoactive medications. INTERVENTIONS: From April 2012 to February
      2014, 53 hemodynamically unstable intensive care unit patients received an
      examination with the miniature transesophageal echocardiography probe when deemed
      necessary by the intensivist for rapid and/or ongoing transesophageal
      echocardiographic examinations. Twenty-eight of the examinations were performed
      in patients with MCS devices (53%). The remainder of examinations (n = 25, 47%)
      were performed in patients after other cardiothoracic surgery or noncardiac
      surgery with cardiac complications. MEASUREMENTS AND MAIN RESULTS: The measured
      endpoint was determination of usefulness of management guidance due to the
      miniature transesophageal echocardiographic examination as assessed by the
      intensivist caring for the patient. The incidence of hTEE imaging provoking a
      change in management also was recorded. Overall, of the 53 examinations, 77% (n =
      41) provided useful information to the management. Of the 25 examinations in
      patients without MCS, 92% (n = 23) of the examinations were useful in guiding
      management. Among the 28 examinations in patients with MCS devices, 64% (n = 18)
      of examinations were useful in guiding management (odds ratio = 0.156; 95%
      confidence interval, 0.015-0.899; p = 0.022). Eight of the 53 examinations (15%)
      were deemed to have "poor image quality" by the echocardiographer. Age, sex, and
      body mass index did not significantly affect the usefulness of the hTEE
      examinations. CONCLUSION: Examination of a heterogeneous hemodynamically unstable
      intensive care population with a miniature transesophageal echocardiography probe
      provided useful information beyond standard intensive care unit monitoring data,
      which influenced post-hTEE medical decision making. The examinations were more
      useful in patients without MCS devices than in those with MCS. Of the patients
      with MCS, patients with durable ventricular assist devices had the lowest rate of
      useful examinations.

PMID- 29174661
TI  - Anesthetic Considerations for Mediastinal Staging Procedures for Lung Cancer.
AB  - Tumor staging is critical for the treatment of lung malignancies. Invasive
      techniques of lung tumor staging can be accomplished via mediastinoscopy,
      endobronchial ultrasound, and video-assisted thoracoscopy. Anesthesiologists
      taking care of patients undergoing mediastinal staging procedures might face
      different challenges. In this narrative review, the authors summarize the
      literature on the anesthetic considerations for mediastinal staging procedures.

PMID- 29174660
TI  - The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights From
      2017.

PMID- 29174662
TI  - Keep Ventilating the Lungs While the Heart is Still Ejecting on Femoro-femoral
      Cardiopulmonary Bypass.
AB  - Femoro-femoral cardiopulmonary bypass (CPB) followed by deep hypothermic
      circulatory arrest is one of the modalities used for ascending aortic
      pseudoaneurysm repair to achieve cardiac unloading and to avoid severe hemorrhage
      due to the risk of rupture during the sternal entry. However, due to the limited
      size of the cannulas, it can be challenging to achieve total cardiopulmonary
      support. Therefore, despite the achievement of total cardiopulmonary support, the
      heart may still be able to eject antegrade blood flow that meets the retrograde
      blood flow from the arterial side of the CPB. The point where the blood flow
      meets in the aorta is called the watershed area. If the antegrade blood flow is
      large due to a left ventricular ejection, the watershed area will be located in
      the descending aorta. Therefore, if ventilation is stopped, deoxygenated blood
      will be ejected to the cerebral circulation. Cerebral near-infrared spectroscopy
      (NIRS) may be used as a noninvasive and continuous measurement of regional brain
      oxygen saturation (rSO2). This case demonstrates that cerebral desaturation due
      to discontinued mechanical ventilation, when the heart was still ejecting during
      the initial phase of femoro-femoral CPB, immediately was detected by a pronounced
      drop bilaterally: In the left frontal lobe, rSO2 fell from 56% to 21%, and in the
      right frontal lobe it fell from 47% to 25%. The authors recommend monitoring
      cerebral saturation using NIRS in the case of femoro-femoral CPB.

PMID- 29174663
TI  - A nationwide survey of French dentists' knowledge and implementation of current
      guidelines for antibiotic prophylaxis of infective endocarditis in patients with
      predisposing cardiac conditions.
AB  - OBJECTIVES: To prevent infective endocarditis in patients with predisposing
      cardiac conditions, antibiotic prophylaxis is recommended worldwide, except in
      the United Kingdom. To determine the relevance of this strategy, investigating
      how the current guidelines are applied is crucial. The first aim of this study
      was to assess dentists' implementation of the current guidelines. The secondary
      aims were to identify relevant areas to improve the training of dentists and to
      determine temporal trends in practitioners' attitudes by comparison with 2
      previous surveys conducted in 1991 and 2001. STUDY DESIGN: An electronic national
      survey was sent to the 12,000 member practitioners of the French Union for Oral
      Health. RESULTS: Even though 58.9% of the respondents stated that their knowledge
      of current guidelines was good, a scoring system showed that only 34.5% had
      overall knowledge of these guidelines. CONCLUSIONS: This study revealed relevant
      areas to improve the training of dentists, such as knowledge of some cardiac
      conditions, the potential side effects of the antibiotics used, and the
      pathogenesis of infective endocarditis. Consequently, dentists' knowledge should
      be improved before any conclusions can be drawn on the relevance of this
      antibiotic prophylaxis strategy and its influence on infective endocarditis
      incidence.

PMID- 29174664
TI  - Measuring E-cigarette dependence: Initial guidance.
AB  - E-cigarette use rates are increasing among youth and adults, despite limited
      knowledge about the safety, risks, and potential for this product in substituting
      for or reducing other tobacco use. Understanding how to characterize and assess e
      cigarette dependence will be important for evaluating the public health impact of
      e-cigarettes and considering prevention and intervention strategies. To provide
      an initial review of constructs to consider when assessing e-cigarette
      dependence, a content expert group within the Tobacco Center for Regulatory
      Science (TCORS) Measurement Workgroup engaged in a review of published
      manuscripts and 12 tobacco dependence measures, followed by review of suggested
      dependence domains by a 10-person external subject-matter expert panel. The final
      domains selected to be considered in the development of a measure of e-cigarette
      dependence included: 1) Quantity and frequency of use, 2) Tolerance, 3) Perceived
      benefits, 4) Withdrawal symptoms, 5) Craving/urge to use, 6) Use despite harm, 7)
      Impaired control, 8) Automaticity, 9) Preferred over competing rewards, and 10)
      Sensory dependence. Similarities and differences in potential features of e
      cigarette dependence compared with dependence on other tobacco products is
      discussed. Future work will evaluate these dependence items and constructs in a
      sample of e-cigarette users with a goal of developing a valid, brief,
      standardized measure of e-cigarette dependence.

PMID- 29174665
TI  - Pro-tobacco advertisement exposure among African American smokers: An ecological
      momentary assessment study.
AB  - INTRODUCTION: Many African Americans live in communities with a
      disproportionately high density of tobacco advertisements compared to Whites.
      Some research indicates that point-of-sale advertising is associated with impulse
      purchases of cigarettes and smoking. Ecological Momentary Assessment (EMA) can be
      used to examine associations between tobacco advertisement exposure and smoking
      variables in the natural environment. METHODS: Non-treatment seeking African
      American smokers were given a mobile device for 2weeks (N=56). They were prompted
      four times per day and responded to questions about recent exposure to tobacco
      advertisements. Participants were also asked to indicate the number of cigarettes
      smoked, and if they made any purchase, or an impulse purchase, since the last
      assessment. Linear mixed models (LMMs) analyzed between- and within-subject
      associations between exposure and outcomes. RESULTS: Participants reported seeing
      at least one advertisement on 33% of assessments. Of those assessments, they
      reported seeing menthol advertisements on 87% of assessments. Between-subject
      analyses revealed that participants who on average saw more advertisements were
      generally more likely to report purchasing cigarettes and to purchase cigarettes
      on impulse. Within-subject analyses revealed that when an individual participant
      reported seeing more advertisements than usual they were more likely to have
      reported purchasing cigarettes, making an impulse purchase and smoking more
      cigarettes during the same period, but not the subsequent time period.
      CONCLUSIONS: Many African American smokers are frequently exposed to pro-tobacco
      marketing. Advertisement exposure is cross-sectionally associated with impulse
      purchases and smoking. Future research should assess prospective associations in
      more detail.

PMID- 29174667
TI  - Metal-organic gel enhanced fluorescence anisotropy for sensitive detection of
      prostate specific antigen.
AB  - In this contribution, we demonstrated that Cu-based metal-organic gel (Cu-MOG)
      was able to serve as a novel amplification platform for fluorescence anisotropy
      (FA) assay for the first time, which was confirmed by the sensitive detection of
      a common cancer biomarker, prostate specific antigen (PSA). The dye-labeled probe
      aptamer (PA) product was adsorbed onto the benzimidazole derivative-containing Cu
      MOG via electrostatic incorporation and strong pi-pi stacking interactions, which
      significantly increased the FA value due to the enlargement of the molecular
      volume of the PA/Cu-MOG complex. With the introduction of target PSA, the FA
      value was obviously decreased on account of the specific recognition between PSA
      and PA which resulted in the detachment of PA from the surface of MOG. The linear
      range was from 0.5-8ng/mL, with a detection limit of 0.33ng/mL. Our work has thus
      helped to demonstrate promising application of MOG material in the fields of
      biomolecules analysis and disease diagnosis.

PMID- 29174668
TI  - Investigation of mode assignment on YVO4 crystal in high temperature region by
      polarized Raman spectroscopy and first principles calculations.
AB  - Polarized Raman spectra for 11 modes in the YVO4 crystal were measured in the
      temperature range from room temperature to 473K, and the mode assignment on Raman
      modes was analyzed using the first-principles calculations. We found that the
      calculated frequency values are in good agreement with the experimental ones. The
      large difference of the temperature line broadening between two peaks (380cm-1
      and 891cm-1) of A1g mode has been reported and it is thought to be due to band
      gap effect in PDOS.

PMID- 29174666
TI  - Combining ecological momentary assessment with objective, ambulatory measures of
      behavior and physiology in substance-use research.
AB  - Whereas substance-use researchers have long combined self-report with objective
      measures of behavior and physiology inside the laboratory, developments in
      mobile/wearable electronic technology are increasingly allowing for the
      collection of both subjective and objective information in participants' daily
      lives. For self-report, ecological momentary assessment (EMA), as implemented on
      contemporary smartphones or personal digital assistants, can provide researchers
      with near-real-time information on participants' behavior and mood in their
      natural environments. Data from portable/wearable electronic sensors measuring
      participants' internal and external environments can be combined with EMA (e.g.,
      by timestamps recorded on questionnaires) to provide objective information useful
      in determining the momentary context of behavior and mood and/or validating
      participants' self-reports. Here, we review three objective ambulatory monitoring
      techniques that have been combined with EMA, with a focus on detecting drug use
      and/or measuring the behavioral or physiological correlates of mental events
      (i.e., emotions, cognitions): (1) collection and processing of biological samples
      in the field to measure drug use or participants' physiological activity (e.g.,
      hypothalamic-pituitary-adrenal axis activity); (2) global positioning system
      (GPS) location information to link environmental characteristics
      (disorder/disadvantage, retail drug outlets) to drug use and affect; (3)
      ambulatory electronic physiological monitoring (e.g., electrocardiography) to
      detect drug use and mental events, as advances in machine learning algorithms
      make it possible to distinguish target changes from confounds (e.g., physical
      activity). Finally, we consider several other mobile/wearable technologies that
      hold promise to be combined with EMA, as well as potential challenges faced by
      researchers working with multiple mobile/wearable technologies simultaneously in
      the field.

PMID- 29174669
TI  - Application of terahertz spectroscopy and theoretical calculation in dimethylurea
      isomers investigation.
AB  - The characteristic absorption spectra of two structural isomers of
      dimethylurea(DMU) in 0.6-1.8 THz region have been measured using terahertz time
      domain spectroscopy (THZ-TDS) at room temperature. Significant differences have
      been found between their terahertz spectra and implied that the THZ-TDS is an
      effective means of identifying structural isomers. To simulate their spectra,
      calculations on single molecule and cluster of 1,1-DMU and 1,3-DMU were
      performed, and we found that the cluster calculations using DFT-D3 method are
      better to predict the experimental spectra. Using the normal mode as
      displacements in redundant internal coordinates and the GaussView program, most
      observed THz vibrational modes are assigned to bending and rocking modes related
      to the intermolecular hydrogen bonding interactions, and twisting mode of ethyl
      groups. The different spectral features of two isomers mainly arise from
      different intermolecular hydrogen bonds resulting from different atom
      arrangements in molecules and different molecule arrangements in crystals. Using
      the reduced-density-gradient (RDG) analysis, the positions and types of
      intermolecular hydrogen bonding interactions in 1,1-DMU and 1,3-DMU crystals are
      visualized. Therefore, we can confirm that THz-TDS can be used as an effective
      means for the recognition of structural isomers and detection of intermolecular
      hydrogen bonding interactions in these crystals.

PMID- 29174670
TI  - Neuroleptic malignant syndrome (NMS) associated with amisulpride and sertraline
      use: A case report and discussion.

PMID- 29174672
TI  - [Aluminic intoxication in chronic hemodialysis. A diagnosis rarely evoked
      nowadays. Clinical case and review of the literature].
AB  - Aluminum intoxication in chronic hemodialysis patients has virtually vanished
      over the last decade. Therefore, the diagnosis is rarely advocated at present.
      Aluminum intoxication in dialysis patients associates to different degrees with
      dialysis encephalopathy, bone disorders and microcytic anemia. We report here the
      observation of a patient receiving intermittent hemodialysis therapy who
      presented with acute encephalopathy. It turned out to be caused by aluminum
      intoxication secondary to a defect in dialysis water treatment. Whatever the
      therapeutic approach, the prognosis of this dramatic complication in hemodialysis
      patients remains poor. In severe cases, only renal transplantation can be able to
      improve clinical outcome. Major sources of aluminum are tap water used for
      dialysis together with a defective water treatment system, and to a minor extent
      oral aluminum-containing phosphate binders and antacids. In the absence of a bone
      biopsy, the diagnosis can be made by measuring serum aluminum or better after a
      desferrioxamine test. Prevention of aluminum overload is of utmost importance. It
      is the responsibility of dialysis centers to provide aluminum-free water and
      dialysis fluid. In case of proven aluminum intoxication, the K/DOQI guidelines
      indicated how to best treat hemodialysis patients, based on long-term
      desferrioxamine infusions during the hemodialysis session. It is recommended to
      implement a stepwise increasing desferrioxamine dosage to prevent an acute
      decompensation with irreversible neurological lesions.

PMID- 29174673
TI  - Surface self-assembly of colloidal crystals for micro- and nano-patterning.
AB  - The controlled patterning of polymeric surfaces at the micro- and nanoscale
      offers potential in the technological development of small-scale devices,
      particularly within the fields of photovoltaics, micro-optics and lab- and organ
      on-chip, where the topological arrangement of the surface can influence a
      system's power generation, optical properties or biological function - such as,
      in the latter case, biomimicking surfaces or topological control of cellular
      differentiation. One of the most promising approaches in reducing manufacturing
      costs and complexity is by exploitation of the self-assembling properties of
      colloidal particles. Self-assembly techniques can be used to produce colloidal
      crystals onto surfaces, which can act as replicative masks, as has previously
      been demonstrated with colloidal lithography, or templates in mold-replication
      methods with resolutions dependent on particle size. Within this context, a
      particular emerging interest is focused on the use of self-assembled colloidal
      crystal surfaces in polymer replication methods such as soft lithography, hot and
      soft embossing and nano-imprint lithography, offering low-cost and high
      resolution alternatives to conventional lithographic techniques. However, there
      are still challenges to overcome for this surface patterning approach to reach a
      manufacturing reliability and process robustness comparable to competitive
      technologies already available in the market, as self-assembly processes are not
      always 100% effective in organizing colloids within a structural pattern onto the
      surface. Defects often occur during template fabrication. Furthermore, issues
      often arise mainly at the interface between colloidal crystals and other surfaces
      and substrates. Particularly when utilized in high-temperature pattern
      replication processes, poor adhesion of colloidal particles onto the substrate
      results in degradation of the patterning template. These effects can render
      difficulties in creating stable structures with little defect that are well
      controlled such that a large variety of shapes can be reproduced reliably. This
      review presents an overview of available self-assembly methods for the creation
      of colloidal crystals, organized by the type of forces governing the self
      assembly process: fluidic, physical, external fields, and chemical. The main
      focus lies on the use of spherical particles, which are favorable due to their
      high commercial availability and ease of synthesis. However, also shape
      anisotropic particle self-assembly will be introduced, since it has recently been
      gaining research momentum, offering a greater flexibility in terms of patterning.
      Finally, an overview is provided of recent research on the fabrication of polymer
      nano- and microstructures by making use of colloidal self-assembled templates.

PMID- 29174671
TI  - Human IGF-I propeptide A promotes articular chondrocyte biosynthesis and employs
      glycosylation-dependent heparin binding.
AB  - BACKGROUND: Insulin-like growth factor I (IGF-I) is a key regulator of
      chondrogenesis, but its therapeutic application to articular cartilage damage is
      limited by rapid elimination from the repair site. The human IGF-I gene gives
      rise to three IGF-I propeptides (proIGF-IA, proIGF-IB and proIGF-IC) that are
      cleaved to create mature IGF-I. In this study, we elucidate the processing of IGF
      I precursors by articular chondrocytes, and test the hypotheses that proIGF-I
      isoforms bind to heparin and regulate articular chondrocyte biosynthesis.
      METHODS: Human IGF-I propeptides and mutants were overexpressed in bovine
      articular chondrocytes. IGF-I products were characterized by ELISA, western blot
      and FPLC using a heparin column. The biosynthetic activity of IGF-I products on
      articular chondrocytes was assayed for DNA and glycosaminoglycan that the cells
      produced. RESULTS: Secreted IGF-I propeptides stimulated articular chondrocyte
      biosynthetic activity to the same degree as mature IGF-I. Of the three IGF-I
      propeptides, only one, proIGF-IA, strongly bound to heparin. Interestingly,
      heparin binding of proIGF-IA depended on N-glycosylation at Asn92 in the EA
      peptide. To our knowledge, this is the first demonstration that N-glycosylation
      determines the binding of a heparin-binding protein to heparin. CONCLUSION: The
      biosynthetic and heparin binding abilities of proIGF-IA, coupled with its
      generation of IGF-I, suggest that proIGF-IA may have therapeutic value for
      articular cartilage repair. GENERAL SIGNIFICANCE: These data identify human pro
      insulin-like growth factor IA as a bifunctional protein. Its combined ability to
      bind heparin and augment chondrocyte biosynthesis makes it a promising
      therapeutic agent for cartilage damage due to trauma and osteoarthritis.

PMID- 29174674
TI  - Knowledge, attitudes, and practices of private sector immunization service
      providers in Gujarat, India.
AB  - BACKGROUND: India is responsible for 30% of the annual global cohort of
      unvaccinated children worldwide. Private practitioners provide an estimated 21%
      of vaccinations in urban centers of India, and are important partners in
      achieving high vaccination coverage. METHODS: We used an in-person questionnaire
      and on-site observation to assess knowledge, attitudes, and practices of private
      immunization service providers regarding delivery of immunization services in the
      urban settings of Surat and Baroda, in Gujarat, India. We constructed a
      comprehensive sampling frame of all private physician providers of immunization
      services in Surat and Baroda cities, by consulting vaccine distributors, local
      branches of physician associations, and published lists of private medical
      practitioners. All providers were contacted and asked to participate in the study
      if they provided immunization services. Data were collected using an in-person
      structured questionnaire and directly observing practices; one provider in each
      practice setting was interviewed. RESULTS: The response rate was 82% (121/147) in
      Surat, and 91% (137/151) in Baroda. Of 258 participants 195 (76%) were
      pediatricians, and 63 (24%) were general practitioners. Practices that were
      potential missed opportunities for vaccination (MOV) included not strictly
      following vaccination schedules if there were concerns about ability to pay (45%
      of practitioners), and not administering more than two injections in the same
      visit (60%). Only 22% of respondents used a vaccination register to record
      vaccine doses, and 31% reported vaccine doses administered to the government. Of
      237 randomly selected vaccine vials, 18% had expired vaccine vial monitors.
      CONCLUSIONS: Quality of immunization services in Gujarat can be strengthened by
      providing training and support to private immunization service providers to
      reduce MOVs and improve quality and safety; other more context specific
      strategies that should be evaluated may involve giving feedback to providers on
      quality of services delivered and working through professional societies to adopt
      standards of practice.

PMID- 29174675
TI  - Designing an immunocyte-targeting delivery system by use of beta-glucan.
AB  - A beta-1,3-d-glucan called Schizophyllan (SPG) can form a novel complex with homo
      oligodeoxynucleotides (ODNs) via the combination of hydrogen bonding and
      hydrophobic interactions. Dectin-1 is a major receptor involved in the
      recognition of beta-1,3-d-glucans and expressed on antigen presenting cells
      (APCs) including macrophages, dendritic cells, monocytes, neutrophils, and a
      subset of T cells. Therefore, the SPG/ODN complex can be used as APCs cell
      specific delivery of functional ODNs including unmethylated CpG sequences (CpG
      ODNs). In fact, CpG-ODN/SPG complex induced high antibody titers when it was
      administered to cynomolgus monkeys as adjutant of influenza vaccine. These
      results indicate that SPG can be an excellent immunocyte-targeting drug delivery
      system.

PMID- 29174676
TI  - Leaf saponins of Quillaja brasiliensis enhance long-term specific immune
      responses and promote dose-sparing effect in BVDV experimental vaccines.
AB  - Saponin-based adjuvants are promising adjuvants that enhance both humoral and T
      cell-mediated immunity. One of the most used natural products as vaccine
      adjuvants are Quillaja saponaria bark saponins and its fraction named Quil A(r).
      Despite that, its use has been restricted for human use due to safety issues. As
      an alternative, our group has been studying the congener species Quillaja
      brasiliensis saponins and its performance as vaccine adjuvants, which have shown
      to trigger humoral and cellular immune responses comparable to Quil A(r) but with
      milder side effects. Here, we studied a semi purified aqueous extract (AE) and a
      previously little characterized saponin-enriched fraction (QB-80) from Q.
      brasiliensis as vaccine adjuvants and an inactivated virus (bovine viral diarrhea
      virus, BVDV) antigen co-formulated in experimental vaccines in mice model. For
      the first time, we show the spectra pattern of the Q. brasiliensis saponins by
      MALDI-TOF, a novel and cost-effective method that could be used to characterize
      different batches during saponins production. Both AE and QB-80 exhibited
      noteworthy chemical similarities to Quil A(r). In addition, the haemolytic
      activity and toxicity were assessed, showing that both AE and QB-80 were less
      toxic than Quil A(r). When subcutaneously inoculated in mice, both fractions
      promoted long-term strong antibody responses encompassing specific IgG1 and
      IgG2a, enhanced the avidity of IgG antibodies, induced a robust DTH reaction and
      significantly increased IFN-gamma production in T CD4+ and T CD8+ cells.
      Furthermore, we have proven herein that AE has the potential to promote dose
      sparing, substantially reducing the dose of antigen required for the BVDV
      vaccines and still eliciting a mixed Th1/Th2 strong immune response. Based on
      these results, and considering that AE is a raw extract, easier and cheaper to
      produce than commercially available saponins, this product can be considered as
      candidate to be escalated from experimental to industrial uses.

PMID- 29174677
TI  - In vivo electroporation enhances vaccine-mediated therapeutic control of human
      papilloma virus-associated tumors by the activation of multifunctional and
      effector memory CD8+ T cells.
AB  - In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines
      as immunotherapeutic approaches to control different types of cancer. EP has been
      associated with increased immune response potency, but its capacity in
      influencing immunomodulation remains unclear. Here we evaluated the impact of in
      vivo EP on the induction of cellular immune responses and therapeutic effects of
      a DNA vaccine targeting human papillomavirus-induced tumors. Our results
      demonstrate that association of EP with the conventional intramuscular
      administration route promoted a more efficient activation of multifunctional and
      effector memory CD8+ T cells with enhanced cytotoxic activity. Furthermore, EP
      increased tumor infiltration of CD8+ T cells and avoided tumor recurrences.
      Finally, our results demonstrated that EP promotes local migration of antigen
      presenting cells that enhances with vaccine co-delivery. Altogether the present
      evidences shed further light on the in vivo electroporation action and its impact
      on the immunogenicity of DNA vaccines.

PMID- 29174678
TI  - An in vitro cell-based potency assay for pharmaceutical type A botulinum
      antitoxins.
AB  - Botulism therapy relies on passive immunization with antitoxin. The mouse
      neutralization test is the only pharmacopeia assay to measure the potency of
      antitoxin preparations. Herein, we present an in vitro cell-based assay for the
      measurement of pharmaceutical type A antitoxin potency. Accuracy, reproducibility
      and compatibility with the mouse bioassay were demonstrated using different
      batches of standard antitoxin and toxin preparations. The established assay may
      substantially reduce the use of laboratory animals in the process of
      pharmaceutical antitoxin production.

PMID- 29174679
TI  - Molecular epidemiology of influenza B virus and implications in immunization
      strategy, Southern Brazil.
AB  - Epidemiological indicators have shown the substantial impact of influenza B (Flu
      B) on the development of severe acute respiratory infection (SARI) and on
      mortality rates. In Brazil, the trivalent vaccine, composed of only one Flu B
      lineage is available. We investigated Flu B infections in clinical samples
      collected by the epidemiological surveillance service of Parana State, Brazil,
      from 2013 to 2016. The Flu B lineages Yamagata- (B/Yam) and Victoria-like (B/Vic)
      were identified using the qRT-PCR assay, and notification forms were reviewed.
      Among 379 Flu B positive samples evaluated, 370 (98%) were characterized as B/Yam
      or B/Vic lineages. Both co-circulated with a frequency of 47% and 53%,
      respectively. B/Yam infected equally both genders, while B/Vic was more frequent
      in females (71%). The median age of patients infected by B/Vic (23y; 11-35) was
      lower than that of patients infected by B/Yam (32y; 12-50). Mismatch between the
      vaccine and the circulating strain was observed in the 2013 season, with a high
      number of SARI cases. B/Vic lineage was associated with a larger number of SARI
      cases (62%), while B/Yam with influenza-like illness (ILI) (61%). Differences
      were observed in the strains circulating in separate regions of Parana State.
      B/Vic was prevalent in the northwestern (67%) and B/Yam in the southeastern
      region (60%). The unpredictability of Flu B lineage circulation causes a
      substantial increase in severe disease during epidemics in a vaccine mismatch
      season. In addition, the differences in the epidemiological profile of the target
      population of Flu B infections in relation to other respiratory viruses, as well
      as among the B/Vic and B/Yam lineages may also be associated to an increase in
      disease burden. These findings have direct consequences on vaccination
      strategies. Therefore, further molecular epidemiology studies of Flu B in Brazil
      are required to corroborate these primary results.

PMID- 29174680
TI  - Impact of measles supplementary immunization activities on reaching children
      missed by routine programs.
AB  - BACKGROUND: Measles supplementary immunization activities (SIAs) are vaccination
      campaigns that supplement routine vaccination programs with a recommended second
      dose opportunity to children of different ages regardless of their previous
      history of measles vaccination. They are conducted every 2-4 years and over a few
      weeks in many low- and middle-income countries. While SIAs have high vaccination
      coverage, it is unclear whether they reach the children who miss their routine
      measles vaccine dose. Determining who is reached by SIAs is vital to
      understanding their effectiveness, as well as measure progress towards measles
      control. METHODS: We examined SIAs in low- and middle-income countries from 2000
      to 2014 using data from the Demographic and Health Surveys. Conditional on a
      child's routine measles vaccination status, we examined whether children
      participated in the most recent measles SIA. RESULTS: The average proportion of
      zero-dose children (no previous routine measles vaccination defined as no
      vaccination date before the SIA) reached by SIAs across 14 countries was 66%,
      ranging from 28% in Sao Tome and Principe to 91% in Nigeria. However, when also
      including all children with routine measles vaccination data, this proportion
      decreased to 12% and to 58% when imputing data for children with vaccination
      reported by the mother and vaccination marks on the vaccination card across
      countries. Overall, the proportions of zero-dose children reached by SIAs
      declined with increasing household wealth. CONCLUSIONS: Some countries appeared
      to reach a higher proportion of zero-dose children using SIAs than others, with
      proportions reached varying according to the definition of measles vaccination
      (e.g., vaccination dates on the vaccination card, vaccination marks on the
      vaccination card, and/or self-reported data). This suggests that some countries
      could improve their targeting of SIAs to children who miss other measles vaccine
      opportunities. Across all countries, SIAs played an important role in reaching
      children from poor households.

PMID- 29174681
TI  - Parental perceptions, attitudes and acceptance of childhood immunization in Saudi
      Arabia: A cross sectional study.
AB  - OBJECTIVES: The widespread availability and use of vaccines have tremendously
      reduced morbidity, mortality and health care costs associated with infectious
      diseases. However, parental beliefs about vaccination are one of the major
      factors in achieving high vaccination rates. Thus, this study aims to assess the
      perceptions and attitudes regarding routine childhood immunization among Saudi
      parents. METHODS: A cross sectional study with a pre-tested 18-item questionnaire
      was conducted using 467 randomly selected parents from the Hail region of Saudi
      Arabia in the period between February 1st, 2016, and February 1st, 2017. The
      validated questionnaire consisted of three sections that collected information on
      participants' demographics, parents' awareness of vaccine benefits, and parents'
      practices regarding the immunization of their children. RESULTS: Female and male
      parents comprised 54.5% (255) and 45.5% (212) of the sample, respectively, and
      the response and completion rates were 97%. The majority of the respondents had
      received a formal education (94.1%, 439), were gainfully employed (62.9%, 294)
      and had a regular monthly income (73.3%). The majority of the respondents were
      aware of childhood vaccinations (78.9%), completed vaccinations mandated for
      children up to 5 years (86.2%), encouraged other parents to do so (89.9%), and
      had easy access to vaccines (90.5%). Sixty to ninety percent of the respondents
      were knowledgeable regarding the health benefits of vaccinations in children,
      even though 18.4% of their children had experienced vaccination-related minor
      adverse effects during or after vaccination of which 23.2% required doctor's
      visits. Health care professionals were the most frequent source of parents'
      vaccine-related information (65.2%), and vaccination reminder services provided
      by the Ministry of Health (MOH) via mobile phones were cited by 57.5% of
      respondents. CONCLUSIONS: Confidence in and acceptance of childhood vaccinations,
      perceptions of vaccine-related health benefits and ease of access to
      immunizations appeared to be quite good among Saudi parents.

PMID- 29174682
TI  - Herpes zoster vaccine live: A 10 year review of post-marketing safety experience.
AB  - BACKGROUND: Zoster vaccine is a single dose live, attenuated vaccine (ZVL)
      indicated for individuals >=50 years-old for the prevention of herpes zoster
      (HZ). Safety data from clinical trials and post-licensure studies provided
      reassurance that ZVL is generally safe and well tolerated. The objective of this
      review was to provide worldwide post-marketing safety information following 10
      years of use and >34 million doses distributed. METHODS: All post-marketing
      adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May
      2016 from healthcare professionals following vaccination with ZVL and submitted
      to the MSD AE global safety database, were analyzed. RESULTS: A total of 23,556
      AE reports, 93% non-serious, were reported. Local injection site reactions
      (ISRs), with a median time-to-onset of 2 days, were the most frequently reported
      AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of
      vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data
      from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ
      confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an
      immunocompetent individual 8 months postvaccination and in 4 immunocompromised
      individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in
      immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as
      VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive
      conditions and/or therapy at the time of vaccination. CONCLUSIONS: The safety
      profile of ZVL, following 10 years of post-marketing use, was favorable and
      consistent with that observed in clinical trials and post-licensure studies.

PMID- 29174684
TI  - Food wasters: Profiling consumers' attitude to waste food in Italy.
AB  - Scientific literature suggests that in developed countries food is predominantly
      wasted at the consumption stage of the food supply chain. This study aims to
      profile consumers' attitude to waste food in Italy investigating households'
      behaviours leading to food waste generation by addressing what is being wasted
      and why it is wasted. The work is based on a survey performed in Italy on a
      heterogeneous sample of 3,087 respondents. A cluster analysis was performed to
      detect consumers' profiles. Results, based on self-reporting, allow to sketch
      different 'waster' types, providing a picture of food waste related to eating,
      shopping, and storage behaviours and suggesting a number of differences existing
      in terms of perceived quantities and causes of generated food waste. Out of seven
      profiles identified, four are the most representative ones in terms of size: the
      conscious-fussy type, who wastes because food doesn't smell or look good; the
      conscious-forgetful type, who forgets what is in the fridge or on the shelves;
      the frugal consumer who tends not to consume fruits and vegetables and declares
      to waste nothing (or almost nothing); and the exaggerated cook, who overbuys and
      overcooks. Profiling specific waste types can help to better understand if groups
      with common characteristics exist, what their specific features are and what
      levers can be employed to stimulate a change in their behaviour.

PMID- 29174683
TI  - Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes
      zoster subunit vaccine administered 2, 6 or 12 months apart in older adults:
      Results of a phase III, randomized, open-label, multicenter study.
AB  - BACKGROUND: In phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine
      (HZ/su; 50 ug varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant
      System) administered 2-months apart in older adults (>=50 and >=70 years)
      demonstrated >90% efficacy in preventing HZ and had a clinically acceptable
      safety profile. Here we report immunogenicity, reactogenicity and safety
      following administration of 2 HZ/su doses at intervals longer than 2 months.
      METHODS: In this Phase III, open-label trial conducted in the US and Estonia, 354
      adults >=50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12
      months apart. gE-specific humoral immune responses were evaluated at pre
      vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare
      immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months
      apart to those administered 2-months apart. For each participant, safety
      information was collected from dose 1 to 12 months post-dose 2. RESULTS: 346
      participants completed the study and 343 were included in the according-to
      protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates
      were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI:
      87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules
      meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean
      concentrations was demonstrated for HZ/su administered on 0, 6-month compared to
      a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did
      not meet the non-inferiority criterion. Injection site pain was the most commonly
      reported solicited adverse event (AE). 26 participants each reported at least 1
      serious AE; none were assessed as related to vaccination. CONCLUSIONS: Immune
      responses to HZ/su administered at 0, 6-month were non-inferior to those elicited
      by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile
      for all dosing intervals. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov
      (NCT01751165).

PMID- 29174685
TI  - Influence on anaerobic digestion by intermediate thermal hydrolysis of waste
      activated sludge and co-digested wheat straw.
AB  - This paper analyses time (30 and 60 min) and temperature (120-190  degrees C)
      effects of intermediate thermal hydrolysis (ITHP) in a two-step anaerobic
      digestion of waste activated sludge (WAS) with and without wheat straw as a co
      substrate. Effects were analyzed by measuring biochemical methane potential for
      60 days and assessing associated kinetic and chemical data. Compared to non
      treatment, ITHP increased the secondary step methane yield from 52 to 222 L CH4
      kg VS-1 and from 147 to 224 L CH4 kg VS-1 for pre-digested WAS and pre-co
      digested WAS respectively at an optimum of 170  degrees C and 30 min. The
      hydrolysis coefficients (khyd) increased by up to 127% following treatment.
      Increasing ITHP time from 30 to 60 min showed ambiguous results regarding methane
      yields, whilst temperature had a clear and proportional effect on the
      concentrations of acetic acid. The energy balances were found to be poor and
      dewatering to increase total solids above the values tested here is necessary for
      this process to be energetically feasible.

PMID- 29174686
TI  - Theory and practice of corrosion related to ashes and deposits in a WtE boiler.
AB  - Corrosion of heat-exchanging components is one of the main operational problems
      in Waste-to-Energy plants, limiting the electrical efficiency that can be
      reached. Corrosion is mainly related to the devolatilization and/or formation of
      chlorides, sulphates and mixtures thereof on the heat-exchanging surfaces.
      Theoretical considerations on this corrosion were already put forward in
      literature, but this paper now for the first time combines theory with a large
      scale sampling campaign of several Waste-to-Energy plants. Based on the outcome
      of elemental and mineralogical analysis, the distribution of Cl and S in ashes
      sampled throughout the plant during normal operation is explained. Cl
      concentrations are high (15-20%) in the first empty pass, decrease in the second
      and third empty pass, but increase again in the convective part, whereas the S
      concentrations show an inverse behavior, with the highest concentrations (30%)
      observed in the second and third empty pass. Sampling of deposits on specific
      places where corrosion possibly occurred, gives a better insight in the
      mechanisms related to corrosion phenomena in real-scale WtE plants and provides
      practical evidence for some phenomena that were only assumed on the basis of
      theory or lab scale experiments before. More specific, it confirms the role of
      oxygen content, temperatures in the different stages of the boiler, the presence
      of polysulphates, Pb and Zb, and the concentrations of HCl and SO2 in the flue
      gas for different types of boiler corrosion.

PMID- 29174687
TI  - Membrane-anchored stalk domain of influenza HA enhanced immune responses in mice.
AB  - Current strategies for influenza virus vaccines primarily aim to elicit immune
      responses towards the globular head domain of the hemagglutinin (HA) protein so
      that binding of the virus to membrane receptors on the host cells is inhibited.
      In the present study, we show a novel strategy to generate immunity against the
      highly conserved region of the influenza virus. The globular head domain was
      replaced by different linkers to generate a headless HA (stalk domain) and then
      coexpressed with influenza M1 proteinin Tni insect cells. The expression was
      validated by western blot analysis, and stalk domain with peptides (GGGGS)4
      linkers was identified to anchor in a stable way to the cell membrane. An
      immunoelectron microscope showed that stalk domain with (GGGGS)4 linkers were
      steadily incorporated to the surface of influenza virus-like particles (VLPs).
      Mice immunized with these VLPs exhibited enhanced systemic antibody responses
      with increased binding avidity and study found high titers of ADCC antibodies to
      the influenza virus, these VLPs also induced mucosal immune responses and
      produced antigen-specific IgG and IgA in nasal and lung washes. In addition,
      antigen-specific IgG antibody-secreting cells (ASCs) increased significantly in
      the spleen and lymph node. The results of this study suggest that the headless HA
      is a useful target in developing a universal vaccine against influenza virus.

PMID- 29174688
TI  - Comparative transcriptome analysis reveals induction of apoptosis in chicken
      kidney cells associated with the virulence of nephropathogenic infectious
      bronchitis virus.
AB  - Avian infectious bronchitis virus (IBV) that causes respiratory and nephritic
      diseases in chicken is a major poultry pathogen leading to serious economic loss
      worldwide. The nephropathogenic IBV strains cause nephritis and kidney lesions
      intrinsically and the pathogenic mechanism is still unclear. In the present
      study, SPF chicks were infected with three nephropathogenic IBVs of different
      virulence and their gene expression profiles in chicken kidney were compared at
      transcriptome level. As a result, 1279 differentially expressed (DE) genes were
      found in very virulent SCDY2 inoculated group, 145 in virulent SCK2 group and 74
      in non-virulent LDT3-A group when compared to mock infected group. Gene Ontology
      (GO) and KEGG pathway enrichment analysis on SCDY2 group displayed that the up
      regulated DE genes were mainly involved in cell apoptosis, and the down-regulated
      genes were involved in metabolic processes and DNA replication. Protein-Protein
      Interaction (PPI) analysis showed that DE genes in SCDY2 group formed a network,
      and the core of the network was composed by cell apoptosis and immune response
      proteins. The clustering of gene expression profile among the three virus
      inoculated groups indicated that the majority of up-regulated DE genes on
      apoptosis in very virulent SCDY2 group were up-regulated more or less in virulent
      SCK2 group and those down-regulated on innate immune response in SCDY2 group were
      also down-regulated differently in SCK2 group. In addition, the number of
      apoptotic cells detected experimentally in kidney tissue were very different
      among the three virus inoculated groups and were positively accordant with the
      viral titer, kidney lesions and viral virulence of each group. Taken all
      together, the present study revealed that virulent nephropathogenic IBV infection
      modified a number of gene expression and induction of apoptosis in kidney cells
      may be a major pathogenic determinant for virulent nephropathogenic IBV.

PMID- 29174689
TI  - Mortality risks from a spectrum of causes associated with wide-ranging exposure
      to fine particulate matter: A case-crossover study in Beijing, China.
AB  - BACKGROUND: Exposure to fine particulate matter (<=2.5MUm in aerodynamic
      diameter; PM2.5) has been shown to be associated with an increased risk of
      mortality due to cardiovascular, respiratory, and other pulmonary diseases.
      However, fewer studies have investigated the relationship between ambient PM2.5
      and human mortality for a wider range of causes of death, or for more specific
      causes of death within these broader categories, especially at the high PM2.5
      concentrations currently experienced in Chinese megacities. Beijing, China, has a
      very large population and a wide range of PM2.5 exposures, allowing a prime
      opportunity to estimate such risks across a broad spectrum of causes, including
      rarer causes of death. OBJECTIVE: To estimate the relative risk of cause-specific
      mortality associated with PM2.5 for a spectrum of causes of death, as well as
      characterize the time course of cause-specific mortality following PM2.5
      exposure, in a location where PM2.5 concentrations are representative of common
      exposures in Chinese megacities. METHODS: We collected daily data on mortality
      counts of Beijing residents and Beijing weather and air pollution measurements
      for January 1, 2009 to December 31, 2012. We used a time-stratified case
      crossover study design to estimate the association between ambient PM2.5
      concentrations and risk of death from several broad causes of death and from more
      refined specific causes within these broader categories. Primary results were
      estimated for risks the day of and the day following exposure (lag 0-1), but the
      time pattern of associated risk was also explored up to seven days following
      exposure. RESULTS: Increased concentrations of PM2.5 were associated with
      increased risks at lag days 0-1 of all-cause mortality (0.26% increase per
      10MUg/m3; 95% confidence interval [CI]: 0.12%-0.39%), non-accidental deaths
      (0.25%; 95% CI: 0.11%-0.38%), circulatory deaths (0.39%; 95% CI: 0.21%-0.59%),
      respiratory deaths (0.43%; 95% CI: 0.05%-0.81%), intentional self-harm deaths
      (1.94%; 95% CI: 0.19%-3.73%) and nervous system deaths (0.9%; 95% CI: -0.2%-2%),
      although the observed increase was not statistical significant for the final one
      rarer cause of death. In addition to these five broad death outcomes, risk also
      increased following PM2.5 exposure at lag days 0-1 for deaths from several
      specific causes, including most of the specific circulatory causes considered.
      The largest observed increased risk by far was for one of the rarest causes of
      death considered, extrapyramidal and movement disorders (2.35%; 95% CI: 0.03%
      4.72%). CONCLUSIONS: This study indicates that exposure to PM2.5 in a study
      location more representative of exposures in developing cities is associated with
      an increased risk of mortality from broad range of causes of death, including
      some causes rarely studied previously in association with PM2.5 exposure.

PMID- 29174690
TI  - Lithium Toxicity after Roux-en-Y Gastric Bypass is Not Just Limited to
      Perioperative Period.

PMID- 29174691
TI  - [Comparison of operative and oncologic results between partial nephrectomy and
      radiofrequency ablation for treatment of renal tumors in patients older than 75].
AB  - INTRODUCTION: Elderly patients represent a growing part of our society for who
      treatment strategy for localized renal tumors has to be chosen knowing iatrogen
      effects and renal function morbidity. The aim was to analyze oncological and
      functional results of nephron sparing surgery (PN) versus radiofrequency ablation
      (RFA). MATERIALS AND METHODS: All patients aged more than 75 treated by partial
      nephrectomy or radiofrequency ablation between 2007 and 2014 in our centre were
      included. Patient and tumors data were compared and these criteria were analyzed:
      survival (overall and without recurrence) and loss of renal function (pre- and
      postoperative MDRD). RESULTS: In total, 100 patients were included (26 partial
      nephrectomies, group 1 and 74 radiofrequency ablation, group 2) with a 32-months
      medium follow-up. Medium age and tumor size were significantly different
      (respectively, 78 versus 81 years old, P=0.001, 38mm versus 29mm, P=0.003).
      Perioperative results showed no differences in complications. Transfusion rate
      and duration of hospital stay were significantly higher in the PN group. Median
      overall survival were 45 vs. 27 months (P=0.23) for PN and RFA and median
      recurrence-free survival were 28 vs. 10 months (P=0.34). On a multivariate
      analysis, operative technique (PN or RFA) were not significantly linked to
      survival (HR 2.37 [95% CI: 0.66-8.5]), P=0.19. Loss of renal function were 1.5+/
      14mL/min/1.73m2 for PN and 3+/-14mL/min/1.73m2 for RFA (P=0.69). CONCLUSION: Our
      study showed better perioperative results for RFA than for PN, without
      significant different survival. Loss of renal function were little and similar.
      LEVEL OF EVIDENCE: 4.

PMID- 29174692
TI  - Increased serum production of soluble CD163 and CXCL5 in patients with moyamoya
      disease: Involvement of intrinsic immune reaction in its pathogenesis.
AB  - Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by a
      progressive stenosis at the terminal portion of the internal carotid artery and
      an abnormal vascular network at the base of the brain. Although its etiology is
      still unknown, intrinsic immune reactions such as autoimmune response has been
      implicated in the pathogenesis of MMD. Recently, the RING finger protein 213
      (RNF213) was found to be an important risk gene for MMD, and is predominantly
      expressed in blood cells and the spleen. Thus, we hypothesized that patients with
      MMD represent an intrinsic autoimmune status mediated by M2-polarized
      macrophages, which play an important role in tissue remodeling and angiogenesis.
      We compared the serum level of soluble (s)CD163, an activating marker for CD163+
      M2-polarized macrophages that has been implicated in a variety of autoimmune
      disorders, between MMD patients and healthy controls. We also analyzed serum
      levels of CXCL5, an augmented cytokines that has been correlated with the
      severity of autoimmune diseases. As a result, the serum sCD163 levels of MMD
      patients (281,465 pg/ml) were significantly higher than those of healthy controls
      (174,842 pg/ml) (p = .004). The serum CXCL5 levels of MMD patients (679.02 pg/ml)
      were significantly higher than those of healthy controls (401.79 pg/ml) (p =
      .046). There were no differences in the serum sCD163 and CXCL5 levels between
      each genotype of the RNF213 polymorphism (wild-type or variant) among MMD
      patients. Although this is a pilot study and further validation with larger
      number of samples is necessary, our results indicate that patients with MMD may
      have increased autoimmune activity, and our results shed light on the
      pathogenesis of MMD via CD163+ M2-polarized macrophages.

PMID- 29174693
TI  - Impact of 36 h of total sleep deprivation on resting-state dynamic functional
      connectivity.
AB  - Resting-state functional magnetic resonance imaging (fMRI) studies using static
      functional connectivity (sFC) measures have shown that the brain function is
      severely disrupted after long-term sleep deprivation (SD). However, increasing
      evidence has suggested that resting-state functional connectivity (FC) is dynamic
      and exhibits spontaneous fluctuation on a smaller timescale. The process by which
      long-term SD can influence dynamic functional connectivity (dFC) remains unclear.
      In this study, 37 healthy subjects participated in the SD experiment, and they
      were scanned both during rested wakefulness (RW) and after 36 h of SD. A sliding
      window based approach and a spectral clustering algorithm were used to evaluate
      the effects of SD on dFC based on the 26 qualified subjects' data. The outcomes
      showed that time-averaging FC across specific regions as well as temporal
      properties of the FC states, such as the dwell time and transition probability,
      was strongly influenced after SD in contrast to the RW condition. Based on the
      occurrences of FC states, we further identified some RW-dominant states
      characterized by anti-correlation between the default mode network (DMN) and
      other cortices, and some SD-dominant states marked by significantly decreased
      thalamocortical connectivity. In particular, the temporal features of these FC
      states were negatively correlated with the correlation coefficients between the
      DMN and dorsal attention network (dATN) and demonstrated high potential in
      classification of sleep state (with 10-fold cross-validation accuracy of 88.6%
      for dwell time and 88.1% for transition probability). Collectively, our results
      suggested that the temporal properties of the FC states greatly account for
      changes in the resting-state brain networks following SD, which provides new
      insights into the impact of SD on the resting-state functional organization in
      the human brain.

PMID- 29174694
TI  - Synergistic promoting effects of bone morphogenetic protein 12/connective tissue
      growth factor on functional differentiation of tendon derived stem cells and
      patellar tendon window defect regeneration.
AB  - Current study investigated bone morphogenetic protein 12 (BMP12) and connective
      tissue growth factor (CTGF) activate tendon derived stem cells (TDSCs) tenogenic
      differentiation, and promotion of injured tendon regeneration. TDSCs were
      transfected with BMP12 and CTGF via recombinant adenovirus (Ad) infection. Gene
      transfection efficiency, cell viability and cytotoxicity, tenogenic gene
      expression, collagen I/III synthesis were evaluated in vitro. For the in vivo
      study, the transfected cells were transplanted into the rat patellar tendon
      window defect. At weeks 2 and 8 of post-surgery, the repaired tendon tissues were
      harvested for histological and biomechanical examinations. The transfected TDSCs
      revealed relatively stable transfection efficiency (80-90%) with active cell
      viability means while rare cytotoxicity in each group. During days 1 and 5, BMP12
      and CTGF transfection caused tenogenic differentiation genes activation in TDSCs:
      type I/III collagen, tenascin-C, and scleraxis were all up-regulated, whereas
      osteogenic, adipogenic, and chondrogenic markers were all down-regulated
      respectively. In addition, BMP12 and CTGF overexpression significantly promote
      type I/III collagen synthesis. After in vivo transplantation, at 2 and 8 weeks
      post-surgery, BMP12, CTGF and co-transfection groups showed more integrated
      tendon tissue structure versus control, meanwhile, the ultimate failure loads and
      Young's were all higher than control. Remarkably, at 8 weeks post-surgery, the
      biomechanical properties of co-transfection group was approaching to normal rat
      patellar tendon, moreover, the ratio of type III/I collagen maintained about 20%
      in each transfection group, meanwhile, the type I collagen were significantly
      increased with co-transfection treatment. In conclusion, BMP12 and CTGF
      transfection stimulate tenogenic differentiation of TDSCs. The synergistic
      effects of simultaneous transfection of both may significantly promoted rat
      patellar tendon window defect regeneration.

PMID- 29174695
TI  - Use of oral cholera vaccine as a vaccine probe to define the geographical
      dimensions of person-to-person transmission of cholera.
AB  - BACKGROUND: Cholera is known to be transmitted from person to person, and
      inactivated oral cholera vaccines (OCVs) have been shown to confer herd
      protection via interruption of this transmission. However, the geographic
      dimensions of chains of person-to-person transmission of cholera are uncertain.
      The ability of OCVs to confer herd protection was used to define these dimensions
      in two cholera-endemic settings, one in rural Bangladesh and the other in urban
      India. METHODS: Two large randomized, placebo-controlled trials of inactivated
      OCVs, one in rural Matlab, Bangladesh and the other in urban Kolkata, India, were
      reanalyzed. Vaccine herd protection was evaluated by relating the risk of cholera
      in placebo recipients to vaccine coverage of surrounding residents residing
      within concentric rings. In Matlab, concentric rings in 100-m increments up to
      700m were evaluated; in Kolkata, 50-m increments up to 350m were evaluated.
      RESULTS: One hundred and eight cholera cases among 24667 placebo recipients were
      detected during 1year of post-vaccination follow-up at Matlab; 128 cholera cases
      among 34968 placebo recipients were detected during 3 years of follow-up in
      Kolkata. Consistent inverse relationships were observed between vaccine coverage
      of the ring and the risk of cholera in the central placebo recipient for rings
      with radii up to 500m in Matlab and up to 150m in Kolkata. CONCLUSIONS: These
      results suggest that the dimensions of chains of person-to-person transmission in
      endemic settings can be quite large and may differ substantially from setting to
      setting. Using OCVs as 'probes' to define these dimensions can inform
      geographical targeting strategies for the deployment of these vaccines in endemic
      settings.

PMID- 29174696
TI  - Corrigendum to "Mathematical analysis of a cholera model with public health
      interventions" [Biosystems, 105 (3) (2011), 190-200].

PMID- 29174697
TI  - Prevalence of Nonmedical Use of Prescription Opioids and Association With Co
      occurring Substance Use Disorders Among Adolescents in Substance Use Treatment.
AB  - PURPOSE: We sought to describe the prevalence of the nonmedical use of
      prescription opioids (NMUPO) and its association with co-occurring substance use
      disorders in a sample of adolescents in substance treatment. METHODS: Adolescents
      in two substance treatment programs were recruited for participation between 2009
      and 2013. The Composite International Diagnostic Interview-Substance Abuse Module
      (CIDI-SAM) was administered to assess substance use patterns and lifetime abuse
      or dependence. RESULTS: A total of 378 adolescents completed the CIDI-SAM (mean
      age 16.1 [standard deviation = 1.1], 78% male, 50% white, non-Hispanic). Of the
      378 adolescents, 62 (16.4%) reported NMUPO and 59 (15.6%) were diagnosed with
      opioid/heroin abuse or dependence. The mean age at first NMUPO was 14.3 (standard
      deviation = 1.4). NMUPO was associated with a 3.31-fold (95% confidence interval:
      2.83-3.79) increase in having three or more co-occurring substance use diagnoses.
      CONCLUSIONS: NMUPO is quite prevalent among adolescents in substance use
      treatment. Intervention to interrupt NMUPO from progressing to heroin use or
      developing into a disorder is critical.

PMID- 29174698
TI  - Biofabrication of gold nanoparticles by Lyptolyngbya JSC-1 extract as super
      reducing and stabilizing agents: Synthesis, characterization and antibacterial
      activity.
AB  - This study describes the first ever utilization of cell free aqueous extract of
      cyanobacterium Leptolyngbya JSC-1 as a source of strong reducing and stabilizing
      agents for the optimal biofabrication of gold nanoparticles (AuNPs) through an
      eco-friendly synthetic route. Well dispersed crystalline AuNPs of spherical
      morphology with a particle size of 100-200 nm were prepared. FTIR spectral
      analysis was then performed to characterize the possible functionalities of JSC-1
      extract, mainly involved in stabilizing and formation of AuNPs. Based on the
      redox potential of JSC-1 extract, it was further confirmed that the extract
      provide a strong reducing environment in the reaction medium and causes reduction
      of gold ions. The resultant AuNPs were then explored to find out their photo
      catalytic activity for methylene blue and antibacterial activities against E.
      coli (18 +/- 2 mm) and S. aureus (14 +/- 2 mm). It has been mechanistically
      identified that AuNPs caused bacterial membrane damage and cell disruption by
      inducing the production of intracellular reactive oxygen species (ROS). Together,
      these finding reveals that biochemically capped AuNPs are the promising
      antibacterial agents that induce oxidative stress in the two bacterial species
      evaluated and cause their membrane disruption leading to cell leakage and death.

PMID- 29174699
TI  - Neoteric advancement in TB drugs and an overview on the anti-tubercular role of
      peptides through computational approaches.
AB  - Tuberculosis (TB) is a devastating threat to human health whose treatment without
      the emergence of drug resistant Mycobacterium tuberculosis (M. tuberculosis) is
      the million-dollar question at present. The pathogenesis of M. tuberculosis has
      been extensively studied which represents unique defence strategies by infecting
      macrophages. Several anti-tubercular drugs with varied mode of action and
      administration from diversified sources have been used for the treatment of TB
      that later contributed to the emergence of multidrug-resistant tuberculosis (MDR
      TB) and extensively drug-resistant tuberculosis (XDR-TB). However, few of potent
      anti-tubercular drugs are scheduled for clinical trials status in 2017-2018.
      Peptides of varied origins such as human immune cells and non-immune cells,
      bacteria, fungi, and venoms have been widely investigated as anti-tubercular
      agents for the replacement of existing anti-tubercular drugs in future. In the
      present review, we spotlighted not only on the mechanisms of action and mode of
      administration of currently available anti-tubercular drugs but also the recent
      comprehensive report of World Health Organization (WHO) on TB epidemic,
      diagnosis, prevention, and treatment. The major excerpt of the study also
      inspects the direct contribution of different computational tools during drug
      designing strategies against M. tuberculosis in order to grasp the interplay
      between anti-tubercular peptides and targeted bacterial protein. The potentiality
      of some of these anti-tubercular peptides as therapeutic agents unlocks a new
      portal for achieving the goal of end TB strategy.

PMID- 29174700
TI  - Sub-inhibitory concentrations of fluoroquinolones increase conjugation frequency.
AB  - Bacteria are subjected to sub-minimal inhibitory concentrations (sub-MIC) of
      antibiotics in various niches where the low-dosage treatment plays a key role in
      antibiotic resistance selection. However, the mechanism of sub-MIC of antibiotics
      on the resistant gene transfer is largely unknown. Here, we used Escherichia coli
      SM10lambdapir in which the RP4 plasmid was chromosomally-integrated as the donor
      strain, to investigate the effects of sub-MIC of Ciprofloxacin(Cip) or
      Levofloxacin(Lev) on conjugational transfer of mobilisable plasmid-pUCP24T from
      SM10lambdapir to Pseudomonas aeruginosa. The results showed that the transfer
      frequency was significantly increased by treating E. coli with sub-MIC of Cip or
      Lev. To investigate the molecular mechanisms, complete transcriptome sequencing
      was performed. We found that the sub-MIC of Cip or Lev enhanced the expression of
      several genes on the RP4 plasmid, which was consistent with the conjugation
      efficiency. Moreover, the expression of genes associated with SOS response in
      donor SM10lambdapir was increased, but had no correlation with conjugation
      efficiency. These findings suggested that sub-MIC of Cip or Lev may promote
      conjugational transfer by up-regulating the expression of conjugation associated
      genes via an SOS-independent mechanism.

PMID- 29174701
TI  - Tadpoles fed supplemented diet with probiotic bacterium isolated from the
      intestinal tract of bullfrog Lithobates catesbeianus: Haematology, cell activity
      and electron microscopy.
AB  - The aim of this study is to select and isolate autochthonous bacteria with
      probiotic potential for use in a supplemented diet for bullfrog tadpoles,
      Lithobates catesbeianus. A total of 20 strains of lactic acid bacteria were
      isolated. Nine out of these were used in the following in vitro assays:
      antagonism against pathogenic bacteria (ANT), antimicrobial activity from
      extracellular compounds (MIC), tolerance to bile salts (TBS), pH reduction,
      protease production, sensitivity to antimicrobial tetracycline, cell viability,
      growth rate and doubling time. Using these data was defined an ideotype (ideal
      strain) based on the best results. Distances were estimated with the Mahalanobis
      (D2) test, and the best candidates, presenting the shortest ideotype distances,
      were considered to be used. The best strain was found to be Lactobacillus
      plantarum because it presented 10.00 +/- 0.50 mm of ANT against Aeromonas
      hydrophila, 3.99 +/- 0.01 of MIC independent of pathogenic bacteria, 85.07 +/-
      0.01 of TBS, 4.20 +/- 0.02 of final pH, 17.67 +/- 1.15 of protease production,
      13.50 +/- 2.00 sensitivity to antimicrobial tetracycline, 9.36 +/- 0.04 of cell
      viability, 0.20 +/- 0.00 of growth rate and 3.46 +/- 0.00 doubling time.
      Therefore this probiotic candidate was then supplemented (2.045 +/- 1.07 * 107
      colony forming unities. g-1) into the diets of bullfrog tadpoles for a period of
      42 days. At the end of the trial, samples of blood and intestines were collected
      to verify the haematological alterations and the intestinal morphology using
      transmission and scanning electron microscopy. Tadpoles fed the supplemented diet
      showed successful lactic acid bacterium colonisation, an increased number of
      circulating thrombocytes, monocytes, eosinophil and LG-PAS+ and also an increase
      in the length and density of intestinal microvilli. This study shows the
      feasibility of using probiotics isolated from farmed bullfrogs as a supplement in
      the diets of tadpoles, providing a promising alternative for modulating the
      health of these animals.

PMID- 29174702
TI  - Cytokine induction of peripheral blood mononuclear cells by biofilms and biofilm
      supernatants of Granulicatella and Abiotrophia spp.
AB  - Granulicatella and Abiotrophia species are the normal oral flora bacteria that
      can occasionally cause infective endocarditis. Although substantial data exists
      in the literature demonstrating occurrence of these species in infective
      endocarditis, only a few mechanistic studies on their pathogenicity are found.
      The aim of this study was to investigate the ability of Granulicatella and
      Abiotrophia species to elicit immune response from human peripheral blood
      mononuclear cells (PBMC). Biofilms and biofilm supernatants of Granulicatella
      elegans CCUG 38949, Granulicatella adiacens CCUG 27809 and Abiotrophia defectiva
      CCUG 27639 were used to stimulate PBMCs for 24 h. Cytokines produced were first
      screened using a human cytokine membrane array kit. Further, pro-inflammatory
      cytokines TNF-alpha, IL-beta, and IL-17 were quantified by ELISA. The cytokine
      profiler array showed the induction of 15 different cytokines/chemokines
      including IL-1beta, IL-6, IL-8, TNF-alpha, MCP-1, MIP-1alpha/MIP-1beta and
      RANTES. ELISA quantification revealed that G. adiacens biofilm induced
      significantly higher (P < 0.05) levels of IL-1beta, i.e., 1931 (183) pg/ml than
      G. elegans or A. defectiva. However, in the case of biofilm supernatants A.
      defectiva was the strongest, inducing 2104 (574) pg/ml. Biofilm supernatants, but
      not biofilms from all three species induced TNF-alpha only weakly. IL-17 was
      undetectable from any of the stimulated samples. In conclusion, Granulicatella
      and Abiotrophia are potent inducers of inflammatory mediators from human PBMCs.
      However, biofilms and biofilm supernatants from these species seem to selectively
      elicit stimulation of certain cytokines.

PMID- 29174703
TI  - Heterogeneity of cytolethal distending toxin sequence types of Campylobacter
      jejuni and correlation to invasion/cytotoxicity potential: The first molecular
      survey from Iran.
AB  - The aim of this study was to evaluate the cytotoxicity and attachment/invasion
      potential of thermophilic Campylobacter isolates regarding their cdtABC sequence
      types and virulence-associated gene content. A total of 33 Campylobacter spp.
      were identified from 750 stool samples isolated from patients characterized with
      diarrhea. The prevalence rates of flaA, ciaB, and pldA genes among the isolates
      were 97, 100, and 15%, respectively. The iam gene was found in 100% of the C.
      coli isolates while it was not detected in C. jejuni isolates. Four PCR primer
      pairs jointly amplifying the entire cdtABC genes array and sequence analysis
      revealed variations dispersed along the sequence array. The isolates attachment
      to HeLa cells ranged from 89 +/- 2-100%, and the range of invasions was also from
      0 to 11 +/- 0.04%. The cytotoxicity value was between 2 and 32 in cdt+ isolates
      with no significant correlation to any of the cdtABC sequence types. Moreover,
      the cdtABC encoding strains had increased invasion to HeLa cells, and all of the
      related patients presented much higher white and red blood cell shedding in stool
      specimens (P-value<= 0.001). No significant difference was observed between cdt+
      and cdt- isolates in their attachment rate to HeLa cells. About 48% of all the
      Iranian Campylobacter population lacked a complete set of cdtABC genes array,
      suggesting low invasion and cytotoxicity potential of the isolates which are
      heterogeneous in their cdt genes and virulence.

PMID- 29174704
TI  - Diagnostic and therapeutic approach to the hypertensive crisis.
AB  - High blood pressure is a problem with elevated prevalence in the world
      population. The acute forms of presentation are "hypertensive crises," which
      represent a frequent cause for emergency room and primary care consultations.
      Hypertensive crises are divided into hypertensive emergencies and hypertensive
      urgencies, depending on whether or not there is acute damage to the target organ,
      respectively. Each situation has a different prognosis and treatment. More
      specifically, hypertensive emergencies are potentially serious and usually
      require rapid reductions in blood pressure, whereas hypertensive urgencies can be
      treated as outpatients by reducing blood pressure in hours or days. A significant
      number of patients who consult medical professionals regarding a hypertensive
      crisis do not have a prior diagnosis of hypertension; therefore, it is important
      to periodically monitor blood pressure levels in the community.

PMID- 29174705
TI  - Associations between ECG changes and echocardiographic findings in patients with
      acute non-ST elevation myocardial infarction.
AB  - BACKGROUND: ST segment depression (STD) and T wave inversion (TWI) are typical
      electrocardiographic (ECG) findings in non-ST elevation myocardial infarction
      (NSTEMI). In ST elevation myocardial infarction, ST changes represent transmural
      ischemia. The pathophysiological mechanisms of the ECG changes in NSTEMI are
      unclear. PURPOSE: We studied the associations between ECG and the
      echocardiographic findings in NSTEMI patients. METHODS: Twenty patients with
      acute NSTEMI were recruited during their hospital stay. A comprehensive
      echocardiography study was performed. The findings were compared with blinded ECG
      analyses. RESULTS: Nine (45%) patients had STD, and 16 (85%) patients had TWI. In
      multivariable analysis, STD was independently associated with a lower global
      early diastolic strain rate (beta=-5.061, p=0.033). TWI was independently
      associated with lower circumferential strain (beta=0.132, p=0.032). CONCLUSIONS:
      The typical ECG changes in NSTEMI patients were associated with subtle
      echocardiographic changes. STD was related to changes in diastolic function, and
      TWI was associated with systolic deterioration.

PMID- 29174706
TI  - Electrocardiographic scores of severity and acuteness of myocardial ischemia
      predict myocardial salvage in patients with anterior ST-segment elevation
      myocardial infarction.
AB  - BACKGROUND: Terminal "QRS distortion" on the electrocardiogram (ECG) (based on
      Sclarovsky-Birnbaum's Grades of Ischemia Score) is a sign of severe ischemia,
      associated with adverse cardiovascular outcome in ST-segment elevation myocardial
      infarction (STEMI). In addition, ECG indices of the acuteness of ischemia (based
      on Anderson-Wilkins Acuteness Score) indicate myocardial salvage potential. We
      assessed whether severe ischemia with or without acute ischemia is predictive of
      infarct size (IS), myocardial salvage index (MSI) and left ventricular ejection
      fraction (LVEF) in anterior versus inferior infarct locations. METHODS: In STEMI
      patients, the severity and acuteness scores were obtained from the admission ECG.
      Based on the ECG patients were assigned with severe or non-severe ischemia and
      acute or non-acute ischemia. Cardiac magnetic resonance (CMR) was performed 2
      6days after primary percutaneous coronary intervention (pPCI). LVEF was measured
      by echocardiography 30days after pPCI. RESULTS: ECG analysis of 85 patients with
      available CMR resulted in 20 (23%) cases with severe and non-acute ischemia, 43
      (51%) with non-severe and non-acute ischemia, 17 (20%) with non-severe and acute
      ischemia, and 5 (6%) patients with severe and acute ischemia. In patients with
      anterior STEMI (n=35), ECG measures of severity and acuteness of ischemia
      identified significant and stepwise differences in myocardial damage and
      function. Patients with severe and non-acute ischemia had the largest IS,
      smallest MSI and lowest LVEF. In contrast, no difference was observed in patients
      with inferior STEMI (n=50). CONCLUSIONS: The applicability of ECG indices of
      severity and acuteness of myocardial ischemia to estimate myocardial damage and
      salvage potential in STEMI patients treated with pPCI, is confined to anterior
      myocardial infarction.

PMID- 29174707
TI  - Brugada phenocopy associated with diabetic ketoacidosis in two pediatric
      patients.
AB  - Two patients without cardiac history demonstrated type 1 Brugada pattern during
      hospitalization for diabetic ketoacidosis (DKA). Both patients had normalization
      of their ECGs after treatment of marked electrolyte abnormalities and metabolic
      acidosis. In this report, we describe two cases of Brugada phenocopy associated
      with DKA in children.

PMID- 29174708
TI  - Outcomes following completion and salvage surgery for early rectal cancer: A
      systematic review.
AB  - OBJECTIVES: To establish outcomes after completion and salvage surgery following
      local excision in literature published since 2005, to inform decision-making when
      offering local excision. BACKGROUND: Local excision of early rectal cancer aims
      to offer cure while maintaining quality of life through organ preservation.
      However, some patients will require radical surgery, prompted by unexpected poor
      pathology or local recurrence. Consistent definition and reporting of these
      scenarios is poor. We propose the term "salvage surgery" for recurrence after
      local excision and "completion surgery" for poor pathology. METHODS: Electronic
      databases were searched in February 2016. Studies since 2005 describing outcomes
      for radical surgery following local excision of rectal cancer were included.
      Pooled and average values were obtained. RESULTS: A total of 23 studies included
      262 completion and 165 salvage operations. Most completion operations were done
      within 4 weeks; local recurrence rate was 5% and overall disease recurrence rate
      was 14%. The majority of salvage operations for local recurrence were within 15
      months of local excision, often following adjuvant treatment. Re-do local
      excision was used in 15%; APR was the most common radical procedure. Further
      local recurrence was uncommon (3%) but overall disease recurrence rate was 13%.
      Estimated 5-year survival was in the order of 50%. Heterogeneity was high among
      the studies. CONCLUSIONS: Patients undergoing local excision must be informed of
      risks and expected outcomes, but better data on completion and salvage surgery
      are required to achieve this. SYSTEMATIC REVIEW REGISTRATION NUMBER:
      CRD42014014758.

PMID- 29174709
TI  - Exome sequencing of synchronously resected primary colorectal tumours and
      colorectal liver metastases to inform oncosurgical management.
AB  - BACKGROUND: Next generation sequencing technology has facilitated mapping of the
      colorectal cancer genotype and furthered our understanding of metastogenesis. The
      aim of this study was to investigate for conserved and different mutations in the
      exomes of synchronously resected primary colorectal tumour and liver metastases.
      This information could potentially be utilised to guide the treatment of advanced
      disease with the help of biological information from the primary tumour. METHODS:
      We performed exome sequencing of synchronously resected primary colorectal cancer
      and colorectal liver metastases as well as normal colonic mucosa and liver
      parenchyma, from four patients who had received neo-adjuvant chemotherapy, at a
      depth of 50X using the Ion Proton platform. Raw data was mapped to the reference
      genome prior to variant calling, annotation and downstream analysis. RESULTS:
      Exome sequencing identified 585 non-synonymous missense single nucleotide
      variants (SNVs), of which 215 (36.8%) were unique to the primary tumour, 226
      (38.6%) unique to the metastasis and 81 (13.8%) present in patient matched pairs.
      SNVs identified in the ErbB pathway appear to be concordant between primary and
      metastatic tumours. CONCLUSION: Only 13.8% of the metastatic exome can be
      predicted by the genotype of the primary tumour. We have demonstrated concordance
      of a number of SNVs in the ErbB pathway, which may inform selection of
      therapeutic agents in advanced colorectal cancer.

PMID- 29174710
TI  - Understanding the impact and challenges of secondary data analysis.
AB  - Secondary data analysis is commonly defined as the use of datasets, which were
      not collected for the purpose of the scientific hypothesis being tested. Examples
      of datasets range from private insurance claims to nationally administered health
      surveys. The use of secondary data confer several benefits, most notably by
      eliminating many of the financial and logistical obstacles related to primary
      data collection. The issues in using secondary data to answer important clinical
      and health policy questions are complex, but with appropriate and rigorous
      approaches there is an opportunity to produce high-effect research which can
      improve the care of patients with urologic malignancies.

PMID- 29174711
TI  - High immunoexpression of Ki67, EZH2, and SMYD3 in diagnostic prostate biopsies
      independently predicts outcome in patients with prostate cancer.
AB  - INTRODUCTION: Overtreatment is a major concern in patients with prostate cancer
      (PCa). Prognostic biomarkers discriminating indolent from aggressive disease in
      prostate biopsy are urgently needed. We aimed to evaluate the prognostic value of
      Ki67, EZH2, LSD1, and SMYD3 immunoexpression in diagnostic biopsies from a cohort
      of PCa patients with long term follow-up. MATERIALS AND METHODS: A series of 189
      consecutive prostate biopsies diagnosed with PCa (1997-2001) in a cancer center
      was included in the study, with follow-up last updated in November 2016. Biopsies
      were reviewed and graded according to 2016 WHO criteria. Immunohistochemistry was
      performed in the most representative block. Nuclear staining was assessed using
      digital image analysis. Study outcomes included disease-specific, disease-free,
      and progression-free survival. Statistical analysis was tabulated using SPSS
      version 22.0. Survival curves and hazard ratios (HRs) were estimated using Kaplan
      Meyer and Cox-regression models, respectively. Statistical significance was set
      at P<0.05. RESULTS: The proportion of patients who completed the study was
      177/189 (94%). In univariable analysis, high Ki67, EZH2, and SMYD3
      immunoexpression associated with significantly worse disease-specific survival
      (HR = 1.86, 95% CI: 1.05-3.29; HR = 1.87, 95% CI: 1.10-3.27; HR = 2.68, 95% CI:
      1.02-7.92). In multivariable analysis, the 3 biomarkers displayed significantly
      worse DSS adjusted for CAPRA score (HR = 1.78, 95% CI: 1.01-3.16; HR = 1.93, 95%
      CI: 1.12-3.32; HR = 2.71, 95% CI: 1.04-7.10). Among patients with
      low/intermediate risk CAPRA score, high Ki67 immunoexpression identified those
      more prone to experience disease recurrence (HR = 9.20, 95% CI: 1.27-66.44) and
      progression (HR = 2.97, 95% CI: 1.05-8.43). CONCLUSIONS: High Ki67, EZH2, and
      SMYD3 immunoexpression, adjusted for standard clinicopathological parameters,
      independently predicts outcome in patients with PCa, at diagnosis. This might
      assist in discriminating indolent from aggressive PCa, improving treatment
      selection.

PMID- 29174712
TI  - Lugol Chromoendoscopy Detects Esophageal Dysplasia With Low Levels of Sensitivity
      in a High-Risk Region of China.
AB  - BACKGROUND & AIMS: Chromoendoscopy with Lugol dye is used to screen for early
      stage esophageal squamous dysplasia (ESD) and esophageal cancer. However, the
      sensitivity with which Lugol chromoendoscopy detects ESD or esophageal cancer has
      not been fully assessed in large populations in China. METHODS: From 2012 to
      2016, a total of 15,264 residents in rural Hua County, Henan Province, which is a
      high-incidence area of esophageal cancer in China, were screened by Lugol
      chromoendoscopy. Biopsies were collected from endoscopically visualized lesions,
      identified before and after Lugol chromoendoscopy, and analyzed histologically.
      Biopsies were also collected from standard sites in the esophagus (28 and 33 cm
      distal to the incisors) if no abnormalities were found. We calculated the
      sensitivity with which Lugol chromoendoscopy detects esophageal dysplasia and
      carcinoma, using findings from biopsy analysis as the reference standard.
      RESULTS: A total 586 participants were found by biopsy analysis to have ESD or
      more severe lesions. After endoscopy images were reviewed twice, Lugol
      chromoendoscopy sensitivity values for the detection of mild, moderate, and
      severe dysplasia, and esophageal cancer, were 45.9%, 55.3%, 87.0%, and 97.7%,
      respectively. ESDs were most frequently missed by Lugol chromoendoscopy in
      younger patients and men with moderate levels of dysplasia. CONCLUSION: In a
      screening analysis of a general population in China, we found Lugol
      chromoendoscopy to identify individuals with ESD with lower levels of sensitivity
      (46%-87%) than previously believed, although it identified patients with
      esophageal cancer with almost 98% sensitivity. Prospective studies are needed to
      evaluate the clinical significance of esophageal lesions that are not detected by
      endoscopy.

PMID- 29174713
TI  - Fatigue in Inflammatory Bowel Disease Reflects Mood and Symptom-Reporting
      Behavior Rather Than Biochemical Activity or Anemia.

PMID- 29174714
TI  - [Critical view and argumentation on chronic care programs in Primary and
      Community Care].
AB  - The detailed analysis of the chronic care plans developed by the Spanish regional
      health services show a surprising level of uniformity in their design and
      deployment, despite differences between these services. The reviews about
      theoretical models that support it and tools they develop does not provide
      conclusive evidence to support the chronic care models achieve better results
      than another alternatives of care. Although the whole Spanish chronic care plans
      includes assessment proposals no rigorous studies on their effect have been
      published to date. Given that, on the contrary, there is a strong and repeated
      evidence that health systems with Primary Care high performance obtains better
      outcomes, it is necessary to ask about the need to look for alternative models,
      when the proposed goals could be reached strengthen Primary Care.

PMID- 29174715
TI  - The co-occurrence of adverse childhood experiences among children investigated
      for child maltreatment: A latent class analysis.
AB  - Children investigated for maltreatment are particularly vulnerable to
      experiencing multiple adversities. Few studies have examined the extent to which
      experiences of adversity and different types of maltreatment co-occur in this
      most vulnerable population of children. Understanding the complex nature of
      childhood adversity may inform the enhanced tailoring of practices to better meet
      the needs of maltreated children. Using cross-sectional data from the National
      Survey of Child and Adolescent Well-Being II (N=5870), this study employed latent
      class analysis to identify subgroups of children who had experienced multiple
      forms of maltreatment and associated adversities among four developmental stages:
      birth to 23 months (infants), 2-5 (preschool age), 6-10 (school age), and 11-18
      years-old (adolescents). Three latent classes were identified for infants,
      preschool-aged children, and adolescents, and four latent classes were identified
      for school-aged children. Among infants, the groups were characterized by
      experiences of (1) physical neglect/emotional abuse/caregiver treated violently,
      (2) physical neglect/household dysfunction, and (3) caregiver divorce. For
      preschool-aged children, the groups included (1) physical neglect/emotional
      abuse/caregiver treated violently, (2) physical neglect/household dysfunction,
      and (3) emotional abuse. Children in the school-age group clustered based on
      experiencing (1) physical neglect/emotional neglect and abuse/caregiver treated
      violently, (2) physical neglect/household dysfunction, (3) emotional abuse, and
      (4) emotional abuse/caregiver divorce. Finally, adolescents were grouped based on
      (1) physical neglect/emotional abuse/household dysfunction, (2) physical
      abuse/emotional abuse/household dysfunction, and (3) emotional abuse/caregiver
      divorce. The results indicate distinct classes of adversity experienced among
      children investigated for child maltreatment, with both stability across
      developmental periods and unique age-related vulnerabilities. Implications for
      practice and future research are discussed.

PMID- 29174716
TI  - Interaction of HLA-DRB1* alleles and CTLA4 (+49 AG) gene polymorphism in
      Autoimmune Thyroid Disease.
AB  - Autoimmune Thyroid Diseases (AITDs), including Hashimoto's thyroiditis (HT) and
      Graves' disease (GD), arise by the complex interaction of genes and environmental
      factors. The aim of present study was to study the susceptible associations of
      HLA-DRB1* alleles and CTLA4 +49 AG polymorphism in AITD in south India. AITD
      patients (n=235; HT=180; GD=55) and age/sex matched healthy controls (n, 235)
      were enrolled to type HLA-DRB1* alleles and 'CTLA4 +49 AG' by PCR-SSP and PCR
      RFLP methods respectively. Analysis revealed CTLA4 +49 'GG' genotype was
      increased significantly in patients (PL: p=8.7*10-8; HT: p=9.3*10-6; GD:
      p=0.006). Decreased frequencies of 'AA' genotype was observed in patients (PL:
      p=9.4*10-6; HT: p=0.008; GD: p=9.0*10-6). Increased frequencies were observed for
      HLA alleles DRB1*12 (PL: p=1.42*10-10; HT: p=5.75*10-8; GD: p=0.002) and DRB1*11
      (PL: p=0.0025; HT: p=0.013) in patients. Decreased frequencies for alleles
      DRB1*10 (PL: p=0.00002; HT: p=0.018; GD: p=1.63*10-5) and DRB1*03 (PL: p=0.003;
      HT: p=0.003) were observed, suggesting a protective association.
      Combinatorial/Synergistic analysis have revealed an increased frequencies for
      'DRB1*11+AG' (PL: p=0.022), 'DRB1*12+AG' (PL: p=6.1*10-5; HT: p=0.0001),
      'DRB1*04+GG' (PL: p=0.003; HT: p=0.008), 'DRB1*07+GG' (PL: p=0.009; HT: p=0.014)
      and 'DRB1*12+GG' (PL: p=0.005; HT: p=0.005) in patients. However, the
      combinations such as 'DRB1*10+AA' (PL: p=1.8*10-6; HT: p=0.003) and 'DRB1*15+AA'
      (PL: p=0.006; GD: p=0.011) were decreased in patients showing a protective
      association. The 'GG/G' of CTLA4 +49AG SNP, HLA-DRB1*11/-DRB1*12 (DR5) alleles
      and the combinations of DRB1*11/DRB1*12 alleles with AG/GG genotype and
      DRB1*04/07/12 alleles with GG genotype may act as synergistic manner to confer
      the strong susceptibility to AITD in south India.

PMID- 29174717
TI  - Comparison of CyTOF assays across sites: Results of a six-center pilot study.
AB  - For more than five years, high-dimensional mass cytometry has been employed to
      study immunology. However, these studies have typically been performed in one
      laboratory on one or few instruments. We present the results of a six-center
      study using healthy control human peripheral blood mononuclear cells (PBMCs) and
      commercially available reagents to test the intra-site and inter-site variation
      of mass cytometers and operators. We used prestained controls generated by the
      primary center as a reference to compare against samples stained at each
      individual center. Data were analyzed at the primary center, including
      investigating the effects of two normalization methods. All six sites performed
      similarly, with CVs for both Frequency of Parent and median signal intensity
      (MSI) values<30%. Increased background was seen when using the premixed antibody
      cocktail aliquots at each site, suggesting that cocktails are best made fresh.
      Both normalization methods tested performed adequately for normalizing MSI values
      between centers. Clustering algorithms revealed slight differences between the
      prestained and the sites-stained samples, due mostly to the increased background
      of a few antibodies. Therefore, we believe that multicenter mass cytometry assays
      are feasible.

PMID- 29174719
TI  - Contaminant source identification using semi-supervised machine learning.
AB  - Identification of the original groundwater types present in geochemical mixtures
      observed in an aquifer is a challenging but very important task. Frequently, some
      of the groundwater types are related to different infiltration and/or
      contamination sources associated with various geochemical signatures and origins.
      The characterization of groundwater mixing processes typically requires solving
      complex inverse models representing groundwater flow and geochemical transport in
      the aquifer, where the inverse analysis accounts for available site data.
      Usually, the model is calibrated against the available data characterizing the
      spatial and temporal distribution of the observed geochemical types. Numerous
      different geochemical constituents and processes may need to be simulated in
      these models which further complicates the analyses. In this paper, we propose a
      new contaminant source identification approach that performs decomposition of the
      observation mixtures based on Non-negative Matrix Factorization (NMF) method for
      Blind Source Separation (BSS), coupled with a custom semi-supervised clustering
      algorithm. Our methodology, called NMFk, is capable of identifying (a) the
      unknown number of groundwater types and (b) the original geochemical
      concentration of the contaminant sources from measured geochemical mixtures with
      unknown mixing ratios without any additional site information. NMFk is tested on
      synthetic and real-world site data. The NMFk algorithm works with geochemical
      data represented in the form of concentrations, ratios (of two constituents; for
      example, isotope ratios), and delta notations (standard normalized stable isotope
      ratios).

PMID- 29174718
TI  - Z-FA-FMK demonstrates differential inhibition of aquatic orthoreovirus (PRV),
      aquareovirus (CSRV), and rhabdovirus (IHNV) replication.
AB  - Benzyloxycarbonyl-phenylalanyl-alanyl-fluoromethyl ketone (Z-FA-FMK) is a
      protease inhibitor that has been shown to strongly inhibit mammalian
      orthoreovirus replication. Here we explore the ability of Z-FA-FMK to inhibit
      three important yet genetically discrete aquatic fish viruses: chum salmon
      aquareovirus (CSRV), piscine orthoreovirus (PRV), and the rhabdovirus infectious
      hematopoietic necrosis virus (IHNV). Z-FA-FMK significantly attenuated CSRV in
      vitro transcription and infectious yield following low-dose (2-20MUM) exposure,
      yet a relatively high dose (200MUM) was required to completely block CSRV
      replication. For PRV and IHNV, no significant attenuation of in vitro viral
      transcription was observed following low-dose (2-20MUM) exposure; and although
      high dose (200MUM) exposure significantly attenuated both PRV and IHNV
      transcription, neither was completely inhibited. These transcriptional results
      were similarly reflected in IHNV infectious titre observed at 7days post
      exposure. PRV titre is currently undeterminable in vitro; however, in vivo intra
      peritoneal injection of PRV into juvenile Atlantic salmon (Salmo salar) in
      conjunction with 1.5mg/kg Z-FA-FMK did not affect PRV replication as measured by
      blood associated viral transcripts at 14days post challenge. These results
      indicate that aquatic ortho- and aqua-reoviruses appear to possess resilience to
      Z-FA-FMK relative to mammalian orthoreoviruses and suggest that environmental
      parameters or alternative mechanisms for viral replication may affect the
      efficacy of Z-FA-FMK as an antireoviral compound. Further, as Z-FA-FMK has been
      shown to irreversibly inhibit cysteine proteases such as cathepsins B and L in
      vitro at concentrations of <=100MUM, continued replication of IHNV (and possibly
      PRV) at 200MUM Z-FA-FMK suggests that replication of these viruses can occur in a
      cathepsin-independent manner whereas CSRV likely requires cathepsins or similar
      cysteine proteases for successful replication.

PMID- 29174720
TI  - Fungal feruloyl esterases: Functional validation of genome mining based enzyme
      discovery including uncharacterized subfamilies.
AB  - Feruloyl esterases (FAEs) are a diverse group of enzymes that specifically
      catalyze the hydrolysis of ester bonds between a hydroxycinnamic (e.g. ferulic)
      acid and plant poly- or oligosaccharides. FAEs as auxiliary enzymes significantly
      assist xylanolytic and pectinolytic enzymes in gaining access to their site of
      action during biomass saccharification for biofuel and biochemical production. A
      limited number of FAEs have been functionally characterized compared to over 1000
      putative fungal FAEs that were recently predicted by similarity-based genome
      mining, which divided phylogenetically into different subfamilies (SFs). In this
      study, 27 putative and six characterized FAEs from both ascomycete and
      basidiomycete fungi were selected and heterologously expressed in Pichia pastoris
      and the recombinant proteins biochemically characterized to validate the previous
      genome mining and phylogenetical grouping and to expand the information on
      activity of fungal FAEs. As a result, 20 enzymes were shown to possess FAE
      activity, being active towards pNP-ferulate and/or methyl hydroxycinnamate
      substrates, and covering 11 subfamilies. Most of the new FAEs showed activities
      comparable to those of previously characterized fungal FAEs.

PMID- 29174721
TI  - Adjuvant breast radiotherapy: How to trade-off cost and effectiveness?
AB  - INTRODUCTION: A series of health economic evaluations (HEE) has analysed the
      efficiency of new fractionation schedules and techniques for adjuvant breast
      radiotherapy. This overview assembles the available evidence and evaluates to
      what extent HEE-results can be compared. METHODS: Based on a systematic
      literature review of HEEs from 1/1/2000 to 30/10/2016, all cost comparison (CC)
      and cost-effectiveness analyses (CEA) comparing different adjuvant breast
      radiotherapy approaches were analysed. Costs were extracted and converted to Euro
      2016 and costs per QALY were summarized in cost-effectiveness planes. RESULTS:
      Twenty-four publications are withheld, comparing different fractionation
      schedules and/or irradiation techniques or evaluating the value of adding
      radiotherapy. Normofractionation and intensity-modulated, interstitial or
      intraluminal techniques are important cost-drivers. Highest reimbursements are
      observed in the US, but may overestimate the real cost. Hypofractionation is cost
      effective compared to normofractionation, the results of partial breast
      irradiation are less unequivocal. Intra-operative and external beam approaches
      seem the most cost-effective for favourable risk groups, but whole breast
      irradiation is superior in terms of health effect and omission of radiotherapy in
      terms of costs. CONCLUSION: Hypofractionation may be considered the most relevant
      comparator for new strategies in adjuvant breast radiotherapy, with omission of
      radiotherapy as an interesting alternative in the very favourable subcategories,
      especially for partial breast techniques. Although comparison of CC and CEA is
      hampered by the variability in clinical and economic settings, HEE-based evidence
      can guide decision-making to tailor-made strategies, allocating the optimal
      treatment in terms of effectiveness as well as efficiency to the right
      indication.

PMID- 29174722
TI  - Functional progression of patients with neurological diseases in a tertiary
      paediatric intensive care unit: Our experience.
AB  - INTRODUCTION: Neurological diseases explain a considerable proportion of
      admissions to paediatric intensive care units (PICU), and are a significant cause
      of morbidity and mortality. This study aims to analyse the functional progression
      of children with critical neurological conditions. MATERIAL AND METHODS:
      Retrospective descriptive study of children admitted to PICU with neurological
      diseases over a period of 3 years (2012-2014), assessing vital and functional
      prognosis at PICU discharge and at one year according to the Pediatric Cerebral
      and Overall Performance Category scales (PCPC-POPC) and the Functional Status
      Scale (FSS). The results are compared with our previous data (1990-1999), and
      those of the international multicentre PANGEA study. RESULTS: A total of 266
      children were studied. The mortality rate was 3%; the PRISM-III and PIM2 models
      did not show predictive ability. Clinically significant worsening was observed in
      functional health at discharge in 30% of the sample, according to POPC, 15%
      according to PCPC, and 5% according to FSS. After one year, functional
      performance improved according to PCPC-POPC, but not according to FSS. Children
      with no underlying neurological disease had a higher degree of functional
      impairment; this was prolonged over time. We observed a decrease in overall and
      neurocritical mortality compared with our previous data (5.60 vs. 2.1%, P=.0003,
      and 8.44 vs. 2.63%, P=.0014, respectively). Compared with the PANGEA study, both
      mortality and cerebral functional impairment in neurocritical children were lower
      in our study (1.05 vs. 13.32%, P<.0001, and 10.47% vs. 23.79%, P<.0001,
      respectively). CONCLUSIONS: Nearly one-third of critically ill children have
      neurological diseases. A significant percentage, mainly children without
      underlying neurological diseases, had a clinically significant functional impact
      at PICU discharge and after a year. Neuromonitoring and neuroprotection measures
      and the evaluation of functional progression are necessary to improve critical
      child care.

PMID- 29174723
TI  - Corrections.

PMID- 29174724
TI  - Corrections.

PMID- 29174725
TI  - Epstein-Barr Virus (EBV) associated reactive and indeterminate lymphoid
      proliferations in the lymph node.

PMID- 29174726
TI  - Caveats do not constitute contraindications for early excision and grafting of
      deep burns in a well equipped burn centre.

PMID- 29174727
TI  - Evaluation of a multidisciplinary burn care journal club: Lessons learned.
AB  - BACKGROUND: Journal clubs allow discussion of the quality and findings of recent
      publications. However, journal clubs have not historically been
      multidisciplinary. Burn care is recognized as a true collaborative care model,
      including regular multidisciplinary rounds. Since 2011 we have offered a
      multidisciplinary burn journal club at our institution. We present an evaluation
      of the factors that have made the sessions successful to facilitate others to
      commence their own club. METHODS: At the end of each journal club session
      participants anonymously completed a structured evaluation. Five-point scales
      were used to evaluate understanding, meeting objectives, presentation and
      appropriateness of information. Qualitative questions were asked to identify
      beneficial factors, suggestions for improvements, ideas for future sessions and
      feedback for the facilitator. RESULTS: Attendance grew from six to a maximum of
      19. Members included physicians, nurses, dieticians, physiotherapists,
      occupational therapists, social workers, basic scientists and students.
      Presentations were undertaken by all of these disciplines. Ratings improved
      steadily over time. Understanding increased from a score of 4.5 to 4.8; meeting
      objectives from 4 to 4.9; satisfaction with method of presentation from 4.3 to
      4.9 and with level of information from 3 to 4.9. CONCLUSIONS: Over time, the
      journal club has evolved to better meet the needs of our team. Successful
      multidisciplinary journal club implementation requires identification of
      champions and ongoing evaluation. APPLICABILITY OF RESEARCH TO PRACTICE: The
      success of the journal club has been possible through the engagement of the
      entire burn team. Champions within each discipline, facilitated discussion and
      evaluation tools have helped nurture a nonthreatening team based learning
      environment.

PMID- 29174728
TI  - Brain activity elicited by viewing pictures of the own virtually amputated body
      predicts xenomelia.
AB  - BACKGROUND: Xenomelia is a rare condition characterized by the persistent desire
      for the amputation of physically healthy limbs. Prior studies highlighted the
      importance of superior and inferior parietal lobuli (SPL/IPL) and other
      sensorimotor regions as key brain structures associated with xenomelia. We
      expected activity differences in these areas in response to pictures showing the
      desired body state, i.e. that of an amputee in xenomelia. METHODS: Functional
      magnetic resonance images were acquired in 12 xenomelia individuals and 11
      controls while they viewed pictures of their own real and virtually amputated
      body. Pictures were rated on several dimensions. Multivariate statistics using
      machine learning was performed on imaging data. RESULTS: Brain activity when
      viewing pictures of one's own virtually amputated body predicted group membership
      accurately with a balanced accuracy of 82.58% (p = 0.002), sensitivity of 83.33%
      (p = 0.018), specificity of 81.82% (p = 0.015) and an area under the ROC curve of
      0.77. Among the highest predictive brain regions were bilateral SPL, IPL, and
      caudate nucleus, other limb representing areas, but also occipital regions.
      Pleasantness and attractiveness ratings were higher for amputated bodies in
      xenomelia. CONCLUSIONS: Findings show that neuronal processing in response to
      pictures of one's own desired body state is different in xenomelia compared with
      controls and might represent a neuronal substrate of the xenomelia complaints
      that become behaviourally relevant, at least when rating the pleasantness and
      attractiveness of one's own body. Our findings converge with structural
      peculiarities reported in xenomelia and partially overlap in task and results
      with that of anorexia and transgender research.

PMID- 29174729
TI  - Prevalence of the Clostridium difficile BI/NAP1/027 strain across the United
      States Veterans Health Administration.
AB  - OBJECTIVES: The increased incidence and severity of Clostridium difficile
      infection (CDI) are thought to result partly from the emergence of the
      hypervirulent BI/NAP1/027 strain. Limited recent data are available on the
      prevalence of BI/NAP1/027 in the United States (US). The objective of this study
      was to assess the recent prevalence of BI/NAP1/027 within the US Veterans Health
      Administration (VHA). METHODS: Patients with CDI at any Veterans Affairs Medical
      Center found to routinely test for the presence of BI/NAP1/027 during the study
      period were included between 1 June 2011 and 30 June 2016 in this retrospective,
      observational, nationwide study. RESULTS: In total, 7571 patients had 8224
      positive C. difficile tests that had a corresponding BI/NAP1/027 test. Of those,
      there were 1810 (22.0%) presumptive positive for BI/NAP1/027. The overall
      prevalence of BI/NAP1/027 decreased from a high of 26.2% in 2013 to 16.9% in
      2016. Statistically significant reductions in rates from 2012 to 2016 occurred in
      seven of nine US Census Bureau regions. CONCLUSIONS: The prevalence of C.
      difficile with the BI/NAP1/027 strain was 22.0% across the VHA between 2012 and
      2016. Further studies are needed to confirm these results and for continued
      monitoring of the trends in BI/NAP1/027 prevalence.

PMID- 29174730
TI  - How to: identify non-tuberculous Mycobacterium species using MALDI-TOF mass
      spectrometry.
AB  - BACKGROUND: The implementation of MALDI-TOF MS for microorganism identification
      has changed the routine of the microbiology laboratories as we knew it. Most
      microorganisms can now be reliably identified within minutes using this
      inexpensive, user-friendly methodology. However, its application in the
      identification of mycobacteria isolates has been hampered by the structure of
      their cell wall. Improvements in the sample processing method and in the
      available database have proved key factors for the rapid and reliable
      identification of non-tuberculous mycobacteria isolates using MALDI-TOF MS. AIMS:
      The main objective is to provide information about the proceedings for the
      identification of non-tuberculous isolates using MALDI-TOF MS and to review
      different sample processing methods, available databases, and the interpretation
      of the results. SOURCES: Results from relevant studies on the use of the
      available MALDI-TOF MS instruments, the implementation of innovative sample
      processing methods, or the implementation of improved databases are discussed.
      CONTENT: Insight about the methodology required for reliable identification of
      non-tuberculous mycobacteria and its implementation in the microbiology
      laboratory routine is provided. IMPLICATIONS: Microbiology laboratories where
      MALDI-TOF MS is available can benefit from its capacity to identify most
      clinically interesting non-tuberculous mycobacteria in a rapid, reliable, and
      inexpensive manner.

PMID- 29174732
TI  - Disinhibition in learning and memory circuits: New vistas for somatostatin
      interneurons and long-term synaptic plasticity.
AB  - Neural circuit functions involve finely controlled excitation/inhibition
      interactions that allow complex neuronal computations and support high order
      brain functions such as learning and memory. Disinhibition, defined as a
      transient brake on inhibition that favors excitation, recently appeared to be a
      conserved circuit mechanism implicated in various functions such as sensory
      processing, learning and memory. Although vasoactive intestinal polypeptide (VIP)
      interneurons are considered to be the main disinhibitory cells, recent studies
      highlighted a pivotal role of somatostatin (SOM) interneurons in inhibiting
      GABAergic interneurons and promoting principal cell activation. Interestingly,
      long-term potentiation of excitatory input synapses onto hippocampal SOM
      interneurons is proposed as a lasting mechanism for regulation of disinhibition
      of principal neurons. Such regulation of network metaplasticity may be important
      for hippocampal-dependent learning and memory.

PMID- 29174731
TI  - Increased hippocampal fissure width is a sensitive indicator of rat hippocampal
      atrophy.
AB  - OBJECTIVES: Volume loss within the hippocampus is known as the most replicated
      finding of structural brain imaging studies of neuropsychiatric diseases.
      Although voxel-based auto or semi-auto volumetric measurements are widely used in
      the determination of the human hippocampus, the detection of hippocampal atrophy
      in rats is still a dilemma as it relies on a relatively primitive and complex
      approach. In this study, we aimed to develop a convenient way to measure the
      atrophy of the hippocampus in rats. METHODS: Twenty-four male Wistar rats were
      exposed to chronic unpredictable mild stress (CUMS) and a wheel running test
      (WRT) to simulate the conditions of hippocampal volume atrophy and improvement.
      The hippocampal volume and hippocampal fissure (HiF) width were dynamically
      measured using 7 T structural magnetic resonance imaging (MRI) with the grayscale
      method at week 0, 2, 4, and 8. The changes in the hippocampal volume and HiF
      width in rats were compared. In addition, hematoxylin-eosin (HE) staining of the
      HiF was used to verify the MRI findings. RESULTS: The hippocampal volume and the
      HiF width presented opposite trends based on the MRI findings and the histology
      data. The atrophy of the hippocampal subfields was closely related to the
      corresponding increase in the HiF width. CONCLUSION: Determination of the HiF
      width may serve as a sensitive and convenient indicator of rat hippocampal
      atrophy.

PMID- 29174733
TI  - Comparison of the Cepheid GeneXpert CT/NG assay to the Hologic Aptima Combo2
      assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in
      self-collected rectal swabs.
AB  - Self-collected rectal-swabs were tested for CT and NG on GeneXpert CT/NG as
      compared to APTIMA Combo2. Of 448 rectal-swabs, 22 were positive for CT; 7 for NG
      on both assays; two were discordant. Sensitivity and specificity of GeneXpert was
      95.5% and 99.7% for chlamydia, respectively; for gonorrhea both were 100%.

PMID- 29174734
TI  - rpoB gene sequencing highlights the prevalence of an E. miricola cluster over
      other Elizabethkingia species among UK cystic fibrosis patients.
AB  - Difficulties in distinguishing species of the Elizabethkingia genus by MALDI-TOF
      prompted use of rpoB sequencing to investigate species distribution among 44
      isolates from cystic fibrosis (CF) patients. Forty-three isolates from 38
      patients formed a cluster comprising E. miricola and proposed novel species E.
      bruuniana sp. nov., the exception clustering with proposed species E. ursingii
      sp. nov., also part of this wider cluster. All 44 isolates were PCR-positive for
      urease gene ureG, whereas only one of 23 E. anophelis isolates from non-CF
      patients was positive, suggesting that this gene is largely associated with the
      E. miricola cluster. Antibiotic susceptibilities of 12 CF isolates revealed all
      were resistant to beta-lactams with the exception of piperacillin-tazobactam, and
      were only susceptible to minocycline and co-trimoxazole. Pulsed-field gel
      electrophoresis analysis revealed 4 shared strains among 17 CF patients in one
      pediatric clinic, but epidemiological investigations did not support patient-to
      patient transmission except between one sibling pair.

PMID- 29174735
TI  - Comparative study of 3 carbapenem-hydrolysis methods for the confirmation of
      carbapenemase production in Enterobacteriaceae.
AB  - The goals of the study were to examine the analytic and performance parameters of
      2 commercial rapid carbapenem-hydrolysis assays, the beta-CARBA test (Bio-Rad)
      and the Rapid CARB Blue Kit (ROSCO) in comparison with an in-house CARBA NP assay
      for the detection of Carbapenemase-Producing Enterobacteriaceae (CPE). Their
      performance was evaluated following growth on 2 chromogenic CPE screening media.
      The sensitivity was highest (91%) in the beta-CARBA test when used from the
      mSuperCARBATM plates and was lowest when the same test was used from the
      chromIDTM CARBA plates (75%). The specificity was highest in the NP CARBA test in
      both media (96%), followed by the beta CARBA/mSuperCARBATM combination (92%). The
      specificity of the Rapid CARB Blue Kit was as low as 36% when used with the
      chromIDTM CARBA plates. The beta-CARBA test was simple to use and had the
      shortest turn-around time and hand-on time.

PMID- 29174736
TI  - Protein kinase A mediates scopolamine-induced mTOR activation and an
      antidepressant response.
AB  - BACKGROUND: Clinical reports have shown that scopolamine produces a rapid (3-4 d)
      and potent anti-depressive response without severe adverse effects. Animal
      experiments have proven that scopolamine induces mTOR pathway activation in an
      AMPAR dependent manner. The present study aimed to determine the role of PKA in
      scopolamine-induced potentiation of AMPAR, as well as in mTOR pathway activation
      and rapid antidepressant effects. METHODS: We utilized electrophysiological
      recording, Western blotting, and behavior tests to examine the effects of
      scopolamine, the selective M2 cholinergic receptor antagonist methoctramine, and
      H89, a PKA specific inhibitor on AMPAR potentiation, mTOR pathway activation, and
      behavioral responses in a rat depression model of learned helplessness. RESULTS:
      Scopolamine (1MUM) rapidly increased AMPAR-fEPSP amplitudes and membrane GluA1
      expression in CA1 region of hippocampal slices, both of which were abolished by
      H89. Moreover, scopolamine promoted AMPAR phosphorylation on GluA1 ser845, a PKA
      site involved in GluA1 membrane insertion. H89 disrupted both GluA1 ser845
      phosphorylation and mTOR activation, as well as the antidepressant effects of
      scopolamine as determined via forced swim test. Additionally, methoctramine
      mimicked the effects of scopolamine on phosphorylation and counter-depressive
      action in a PKA-dependent manner. LIMITATIONS: Only one test was used to evaluate
      depressive behavior, and gene knock-out rats were not yet utilized to refine our
      hypotheses. CONCLUSION: Our findings revealed that PKA pathway is necessary for
      scopolamine-induced synaptic plasticity and mTOR pathway activation, and
      indicated that a potential M2-PKA mechanism underlies scopolamine's
      antidepressant effects. Such findings suggest that GluA1 ser845 phosphorylation
      may be a trigger event for scopolamine's actions, and that PKA may represent a
      novel target for the treatment of depressive symptoms.

PMID- 29174737
TI  - The role of media in preventing student suicides: A Hong Kong experience.
AB  - INTRODUCTION: In view of the surge of student suicides in March 2016, a large
      scale media involvement was engaged to minimize copycat effects and to
      extensively spread more preventive information. METHODS: Trend differences
      between student suicides in overall as well as youth suicides between 2003 and
      2016 were examined. Impacts of media involvement were examined as to the changes
      of their intensities in reporting student suicides in different manners. Local
      polynomial smoothing method was used to estimate the intensities throughout the
      study period. RESULTS: The intensity of students' suicides has been slowly
      increasing since 2006, which was in contrast to the decreasing trend of overall
      suicide intensity. After our engagement with the media, acute descriptive
      reporting in student suicide news has sharply dropped and remained low since
      then, whereas preventive-reporting has increased sharply in March and April 2016,
      but dropped back to normal afterwards. The higher intensity of preventive
      reporting seemed to have a protective effect on student suicide. LIMITATIONS:
      Data of student suicides in 2016 were substantially extracted from the local
      news, which may not contain complete information. The analyses suggested, but
      could not confirm, a causal relationship between the changes of student suicide
      news-reporting and the incidents of suicides themselves. CONCLUSIONS: The recent
      surge of student suicides in Hong Kong was statistically abnormal. Media
      engagement has changed local suicide news-reporting to become more preventive,
      which could have contributed to the drop of student suicides. It is essential to
      sustain the media's coverage of preventive reporting to maintain its enduring
      effect.

PMID- 29174738
TI  - Symptoms and functioning with aripiprazole once-monthly injection as maintenance
      treatment for bipolar I disorder.
AB  - BACKGROUND: Effects of maintenance treatment with aripiprazole once-monthly 400mg
      (AOM 400) on symptoms and functioning were assessed in adults with bipolar I
      disorder (BP-I) after a manic episode. METHODS: Patients were stabilized on oral
      aripiprazole, cross-titrated to AOM 400, then randomized in a 52-week, double
      blind, placebo-controlled, withdrawal phase. Prespecified secondary outcomes are
      reported: time to hospitalization for mood episode, Young Mania Rating Scale
      (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global
      Impression-Bipolar scale, Functioning Assessment Short Test (FAST), and Brief
      Quality of Life in Bipolar Disorder questionnaire. Time to hospitalization for
      mood episode was analyzed using log-rank test and changes from baseline using
      mixed model for repeated measures or analysis of covariance. RESULTS: AOM 400
      significantly increased time to hospitalization for any mood episode versus
      placebo (P=0.0002). YMRS total scores decreased with oral aripiprazole;
      improvements were maintained with AOM 400. After randomization, YMRS scores
      changed little with AOM 400 but worsened with placebo (P=0.0016), and MADRS
      scores, already low at trial initiation, did not differ between groups. FAST
      score improvements were maintained with AOM 400 but not placebo (P=0.0287).
      LIMITATIONS: Results are generalizable to patients with BP-I stabilized on
      aripiprazole following a manic episode. CONCLUSIONS: Patients with BP-I
      experiencing an acute manic episode exhibited symptomatic and functional
      improvements during stabilization with oral aripiprazole and AOM 400 that were
      maintained with continued AOM 400 treatment but not placebo. AOM 400 is the first
      once-monthly long-acting injectable antipsychotic to demonstrate efficacy in
      maintenance treatment of the manic phase of BP-I.

PMID- 29174739
TI  - Episode accumulation associated with hastened recurrence and delayed recovery in
      bipolar disorder.
AB  - AIMS: Assess episode accumulation (>= 10 prior mood episodes) associations with
      demographic/baseline clinical characteristics and mood episode
      recurrence/recovery in bipolar disorder (BD). METHODS: Stanford BD Clinic
      outpatients enrolled during 2000-2011 were assessed with Systematic Treatment
      Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Among
      recovered and syndromal mood episode patients, we assessed episode accumulation
      associations with demographic/baseline clinical characteristics and with
      recurrence/recovery (by Kaplan-Meier survival analyses, with mediators assessed
      with Cox Proportional Hazard Ratio (HR) analyses). RESULTS: Among all 450 BD
      outpatients, almost twice as many had versus lacked episode accumulation (65.8%
      versus 34.2%), which was less common among 92 recovered versus 193 syndromal mood
      episode patients (51.1% versus 69.9%). Among recovered patients, episode
      accumulation was associated with 14/18 (77.7%) demographic/other baseline
      clinical characteristics, and hastened mood episode recurrence. Among syndromal
      mood episode patients, episode accumulation was associated with 13/18 (72.2%)
      demographic/other baseline clinical characteristics, and delayed mood episode
      recovery. LIMITATIONS: American tertiary BD clinic referral sample. CONCLUSION:
      Studies are needed to confirm episode accumulation is associated with hastened
      mood episode recurrence and delayed mood episode recovery in BD, and to further
      explore its' associations with hastened mood elevation recurrence and delayed
      recovery from depressive and mood elevation episodes, considered separately.

PMID- 29174740
TI  - Retinal changes in patients with major depressive disorder - A controlled optical
      coherence tomography study.
AB  - BACKGROUND: Recent studies on the pathophysiology of major depression (MD)
      indicate that degenerative and inflammatory processes may play a role. This
      finding is supported by magnetic resonance imaging (MRI)-based meta-analysis that
      show volume reductions in circumscribed areas of the brain in patients with MD.
      Using optical coherence tomography (OCT), retinal changes have been demonstrated
      in neurodegenerative disorders. In light of this inflammatory/degenerative
      hypothesis, we tested whether patients with MD exhibit retinal alterations that
      might correlate with the severity and duration of the disease. METHODS: Patients
      with MD and age- and gender-matched healthy controls were recruited for the
      measurement of the total volume and thickness of their retina as well as the
      thicknesses and volumes of five different retinal layers using single-layer
      analysis provided by the spectral-domain-OCT. RESULTS: OCT data from 28 patients
      with MD and 20 healthy controls were available for evaluation. The exploratory
      intra-individual group comparison of the two eyes showed a small but significant
      difference in the retinal total volume (right = 8.69mm3; left = 8.72mm3; p =
      0.03) only in patients with MD. There were no other significant differences
      between the patients with MD and the healthy controls with respect to the OCT
      measurements. LIMITATIONS: The small group size as well as the absence of
      correction for multiple testing due to the exploratory design should be
      considered as limitations of our study. CONCLUSION: While retinal total volume
      differs between the eyes of patients with MD, the comparison of retinal
      parameters between these patients and age- and gender-matched healthy volunteers
      did not show any differences.

PMID- 29174741
TI  - Antidepressant-like effect of zileuton is accompanied by hippocampal
      neuroinflammation reduction and CREB/BDNF upregulation in lipopolysaccharide
      challenged mice.
AB  - BACKGROUND: Recent studies demonstrated beneficial effects of zileuton, a 5
      lipoxygenase (5LO) inhibitor, on some brain diseases in animal models, but the
      role of zileuton in the depression remains unknown. METHODS: We investigated the
      effects of zileuton on depressive behaviors using tail suspension test (TST),
      forced swimming test (FST) and novelty-suppressed feeding test (NSFT) in mice
      injected with lipopolysaccharide (LPS). The 5LO level, activation of microglia,
      NF-kappaB p65, TNF-alpha, IL-1beta, brain-derived neurotrophic factor (BDNF), and
      c-AMP response element-binding protein (CREB) were determined in the mouse
      hippocampus. RESULTS: We firstly found that the expression of hippocampal 5LO was
      gradually increased over LPS exposure and was reversed by fluoxetine
      administration. Zileuton significantly suppressed LPS-induced depressive
      behaviors, evidenced by the decreases in immobility time in TST and FST, as well
      as the latency to feed in NSFT. This treatment pronouncedly alleviated LPS
      induced neuroinflammatory response, characterized by decreased 5LO, suppressed
      activation of microglia, decreased NF-kappaB p65, TNF-alpha and IL-1beta, and
      significantly increased the ratio of p-CREB/CREB or mBDNF/proBDNF in the
      hippocampus of the LPS-challenged mice. CONCLUSIONS: Zileuton abrogates LPS
      induced depressive-like behaviors and neuroinflammation, and enhances CREB/BDNF
      signaling in the hippocampus, suggesting that zileuton could have potential
      therapeutic value for depression.

PMID- 29174742
TI  - Predictors and outcomes of somatization in bipolar I disorder: A latent class
      mixture modeling approach.
AB  - BACKGROUND: Mood disorders are often associated with somatic symptoms. The role
      of somatic symptoms on disease progression in unipolar depression is
      substantially better characterized than that role in bipolar disorder. Moreover,
      the contribution of comorbid anxiety disorders and medical illness is not well
      understood. METHOD: We investigated 527 patients with bipolar I disorder
      clustered within 102 families using a latent class approach. Predictors were
      added stepwise into the model. Anxiety and commonly associated medical illnesses
      were added as covariates. RESULTS: The rate of somatic symptoms in this sample
      was 73% (mean 1.7 symptoms), and 27.3% had a comorbid anxiety disorder. A two
      class model, with a subgroup at high-risk for somatization, gave the best fit to
      the data. Multilevel mixture modeling accounted for family clusters. Somatic
      symptoms were independently associated with disease severity, defined as earlier
      age of first seeking psychiatric help (x = 21.7 vs x = 24.7, p = 0.005) and first
      psychiatric hospitalization (x = 25.7 vs x = 28.2, p = 0.03), greater probability
      of attempting suicide (x = 0.41 vs x = 0.32, p = 0.047), and rapid-cycling
      disease course (x = 0.57 vs x = 0.36, p < 0.001). Persons with few or no somatic
      symptoms were more likely to be hospitalized for severe mania (x = 0.63 vs x =
      0.51; p = 0.013), but did not significantly differ in hospitalization for severe
      depression. LIMITATIONS: The study is correlational. Information on pharmacologic
      interventions and comorbid diseases was limited. CONCLUSIONS: Somatic symptoms in
      bipolar disorder could be an independent indicator for disease severity,
      suicidality, and rapid-cycling disease course. In severe mental illness, somatic
      and psychological symptoms must be jointly addressed.

PMID- 29174743
TI  - Prefrontal glutamatergic emotion regulation is disturbed in cluster B and C
      personality disorders - A combined 1H/31P-MR spectroscopic study.
AB  - BACKGROUND: Personality disorders (PD) belong to the most common and most serious
      mental disorders as regards social dysfunction, inability to work, occurrence of
      comorbidity and suicidal risk. PDs also crucially influence the incidence,
      clinical course and treatment response of mental disorders with high suicidal
      risk, such as depression or substance abuse. One key issue of PD concerns the
      regulation of emotions. METHODS: Both 1H-/31P-Chemical Shift Imaging (CSI) was
      applied in a single session to assess neurochemical markers of glutamate function
      (NAA, Glu) and local energy metabolism (PCr, ATP) in two patient cohorts
      encompassing 22 cluster B (CB) and 21 cluster C (CC) PD patients, whereby 10
      patients of each group were on low-dose antidepressants, and in 60 healthy
      controls (HC). Non-parametric statistical tests and correlation analyses were
      performed to assess disease effects on the metabolites and their relation to
      symptomatology as assessed by SCL-90R self-ratings. RESULTS: Overall comparison
      including Bonferroni correction revealed significant differences of Glu across
      all groups in the dorsolateral prefrontal cortex (DLPFC). The following
      uncorrected results of pairwise tests were obtained: (i) Glu was bilaterally
      increased in the DLPFC in CB patients, whereas it was - together with NAA -
      bilaterally decreased in the DLPFC in CC patients and accompanied by increased
      PCr in the left DLPFC. (ii) NAA and Glu, accompanied by increased PCr, were
      significantly decreased in the dorsomedial prefrontal cortex (DMPFC) in CC
      patients. (iii) NAA was decreased in the right anterior cingulate cortex (ACC) in
      CB patients, and in the left ACC in CC patients with PCr being increased
      bilaterally. (iv) No associations were observed between metabolites and
      psychopathology measures. CONCLUSION: The observations in the DLPFC may reflect a
      neurobiochemical correlate of disturbed cognitive control function in CB and CC
      PD. While the alterations in CB patients suggest increased basal activity, the
      observed patterns in CC patients likely reflect decreased or inhibited activity.
      The alterations of NAA and Glu levels in the ACC and DMPFC indirectly support the
      assumption of disturbed neuronal function in regions involved in social cognition
      and mentalizing abilities in both CB and CC PD. Further studies should include
      the investigation of metabolites of neuronal inhibition (GABA) and the
      examination of treatment effects.

PMID- 29174744
TI  - Distinguishing transient versus stable aspects of depression in New Zealand
      Pacific Island children using Generalizability Theory.
AB  - BACKGROUND: The distinction between temporary versus enduring or state/trait
      aspects of depression is important. More precise distinction would improve
      understanding of the aetiology of depression and those aspects most amenable to
      intervention thus identifying more homogeneous, dynamic targets for clinical
      trials. Generalizability Theory has been proposed as useful for disentangling
      state and trait components of psychopathology. METHODS: We applied
      Generalizability Theory to determine the relative contributions of temporary and
      enduring aspects of depression in a widely used screening measure of depression
      the - 10-item Children's Depression Inventory (CDI-10; Kovacs, 1985).
      Participants were children of Pacific Island descent living in New Zealand (n =
      668). Data were collected at ages - 9, 11, and 14 years. RESULTS: The CDI-10
      demonstrated acceptable generalizability across occasions (G = 0.79) with about
      one third of variance in total scores attributed to temporary and two thirds to
      more enduring aspects of depression. There were no other significant sources of
      error variance. Two items were identified as more sensitive than the remaining
      eight to more dynamic symptoms. LIMITATIONS: Studies with briefer test-retest
      intervals are warranted. Use of this Pacific Island cohort limits
      generalizability of findings to other cultures and ethnicities. No data were
      collected on whether participants had received intervention for depression.
      CONCLUSIONS: While the CDI-10 reliably measures both stable and transient aspects
      of depression in children, the scale does not permit clear distinction between
      them. We advocate application of Generalizability Theory for developing
      state/trait depression measures and determining which existing measures are most
      suitable for capturing modifiable features of depression.

PMID- 29174745
TI  - Stroke After Transcatheter Aortic Valve Replacement: Incidence, Definitions,
      Etiologies and Management Options.
AB  - Neurologic complications after transcatheter aortic valve replacement are
      devastating. The etiologies of stroke in this setting are best addressed in an
      integrated fashion during each phase of the perioperative pathway. The conduct of
      this triphasic approach will continue to be refined to reduce the stroke risks
      even further, given the major focus on aspects such as embolic protection devices
      and valve thrombosis. This neurologic focus in transcatheter aortic valve
      replacement has transformed the investigational approach to neurologic events in
      cardiovascular clinical trials, resulting in novel guidelines for the diagnosis
      and assessment of neurologic injury after cardiovascular interventions.

PMID- 29174746
TI  - Evaluating the Effect on Mortality of a No-Tranexamic acid (TXA) Policy for
      Cardiovascular Surgery.
AB  - OBJECTIVES: The authors stopped using tranexamic acid (TXA) in April 2013. The
      present study aimed to examine the impact of a "no-TXA-use" policy by comparing
      the adverse effects of TXA and clinical outcomes before and after the policy
      change in patients undergoing cardiovascular surgery. DESIGN: A single center
      retrospective cohort study. SETTING: A single cardiovascular center.
      PARTICIPANTS: Patients undergoing cardiovascular surgery between January 2008 and
      July 2015 (n = 3,535). INTERVENTIONS: Patients' outcomes before and after the
      policy change were compared to evaluate the effects of the change. MEASUREMENTS
      AND MAIN RESULTS: The seizure rate decreased significantly after the policy
      change (6.9% v 2.7%, p < 0.001). However, transfusion volumes and blood loss
      volumes increased significantly after the policy change (1,840 mL v 2,030 mL, p =
      0.001; 1,250 mL v 1,372 mL, p < 0.001, respectively). Thirty-day mortality was
      not statistically different (1.6% v 1.4%, p = 0.82), nor were any of the other
      outcomes. Propensity-matched analysis and segmented regression analysis showed
      similar results. CONCLUSIONS: The mortality rate remained the same even though
      the seizure rate decreased after the policy change. Blood loss volume and
      transfusion volume both increased after the policy change. TXA use provides an
      advantageous benefit by reducing the need for blood transfusion.

PMID- 29174747
TI  - Validation of a Mathematical Model of Bidirectional Glenn Circulation With
      Aortopulmonary Collaterals and the Implications for QP/QS Calculation.
AB  - OBJECTIVES: A mathematical model of the oxygen delivery kinetics of the
      bidirectional Glenn (BDG) shunt circulation incorporating aortopulmonary
      collateral (APC) flow was created. The model was used to characterize oxygen
      delivery and compare modeled data to actual patient data obtained using cardiac
      magnetic resonance imaging (MRI) and catheterization. In addition, cardiac MRI
      and catheterization assessment of pulmonary blood flow in the presence of APC
      flow were compared. DESIGN: Mathematical model and retrospective data analysis of
      patients who underwent cardiac MRI and catheterization. The mathematical model is
      based on the concept that APC flow to the lungs is recirculated pulmonary venous
      blood flow, which does not contribute to systemic oxygen delivery. SETTING:
      Single-center, university teaching hospital. PARTICIPANTS: The study included 98
      patients with BDG shunt undergoing cardiac MRI and cardiac catheterization.
      MEASUREMENTS AND MAIN RESULTS: In the absence of APC flow, the pulmonary blood
      flow to systemic blood flow ratio (Qp/Qs) calculated using cardiac
      catheterization data closely matched that obtained with cardiac MRI. In the
      presence of APC flow, Qp/Qs calculated using cardiac catheterization data
      systematically underestimated values obtained with cardiac MRI. A mathematical
      model of BDG shunt oxygen delivery incorporating variable APC flow was created.
      The model provided reasonable prediction of actual patient data for arterial
      blood oxygen, superior vena cava oxygen saturation, and oxygen delivery obtained
      at the time of cardiac catheterization in patients. CONCLUSION: The oxygen
      delivery kinetics of a BDG shunt incorporating variable APC flow can be modeled
      mathematically. Model output can be used to predict blood oxygen saturation after
      coil embolization of APC flow in the cardiac catheterization laboratory.

PMID- 29174748
TI  - Unusual Echolucency Seen After Bacterial Endocarditis.

PMID- 29174749
TI  - Takotsubo Cardiomyopathy Following Induction of Anesthesia for Lung
      Transplantation, an Unexpected Complication.

PMID- 29174750
TI  - Assessment of Pulmonary Edema: Principles and Practice.
AB  - Pulmonary edema increasingly is recognized as a perioperative complication
      affecting outcome. Several risk factors have been identified, including those of
      cardiogenic origin, such as heart failure or excessive fluid administration, and
      those related to increased pulmonary capillary permeability secondary to
      inflammatory mediators. Effective treatment requires prompt diagnosis and early
      intervention. Consequently, over the past 2 centuries a concentrated effort to
      develop clinical tools to rapidly diagnose pulmonary edema and track response to
      treatment has occurred. The ideal properties of such a tool would include high
      sensitivity and specificity, easy availability, and the ability to diagnose early
      accumulation of lung water before the development of the full clinical
      presentation. In addition, clinicians highly value the ability to precisely
      quantify extravascular lung water accumulation and differentiate hydrostatic from
      high permeability etiologies of pulmonary edema. In this review, advances in
      understanding the physiology of extravascular lung water accumulation in health
      and in disease and the various mechanisms that protect against the development of
      pulmonary edema under physiologic conditions are discussed. In addition, the
      various bedside modalities available to diagnose early accumulation of
      extravascular lung water and pulmonary edema, including chest auscultation, chest
      roentgenography, lung ultrasonography, and transpulmonary thermodilution, are
      examined. Furthermore, advantages and limitations of these methods for the
      operating room and intensive care unit that are critical for proper modality
      selection in each individual case are explored.

PMID- 29174751
TI  - Pellagra.

PMID- 29174752
TI  - Acute Coronary Syndrome in Octogenarians: Expect the Unexpected.
AB  - BACKGROUND: Ischemic heart disease is the leading cause of death in the United
      States and the world. Advanced age is the strongest risk factor for ischemic
      heart disease and the best independent predictor for poor outcomes after acute
      coronary syndrome (ACS). Elderly patients are at high risk for ACS, and numerous
      studies have shown that octogenarians in particular experience increased
      morbidity and mortality compared to younger patients. CASE REPORT: We describe a
      case of an 83-year-old woman who presented to the emergency department with a
      chief complaint of sore throat and was found to have a non-ST elevation
      myocardial infarction (NSTEMI) and was treated successfully with primary coronary
      intervention (PCI). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Chest
      pain is a common presenting symptom for ACS, but elderly patients with MI are
      more likely to present with other chief complaints. Only 40% of patients in the
      National Registry of Myocardial Infarction database >= 85 years of age had chest
      pain on initial presentation. Recent studies comparing invasive therapy (PCI or
      coronary artery bypass graft) with optimal medical therapy for patients > 75
      years of age diagnosed with NSTEMI have reported a reduced risk of death and
      major cardiac events with invasive therapy. Emergency physicians should have a
      high level of suspicion for ACS in octogenarians, even in those presenting
      without chest pain. Timely diagnosis and management can improve morbidity and
      mortality in these patients.

PMID- 29174753
TI  - An Unusual Case of Acute Retroperitoneal Hemorrhage: Dissecting Aneurysm of the
      Inferior Pancreaticoduodenal Artery.

PMID- 29174754
TI  - A Randomized Controlled Trial of a Single Dose Furosemide to Improve Respiratory
      Distress in Moderate to Severe Bronchiolitis.
AB  - BACKGROUND: Bronchiolitis is one of the most common disorders of the lower
      respiratory tract in infants. While historically diuretics have been used in
      severe bronchiolitis, no studies have looked directly at their early use in
      children in the emergency department. OBJECTIVE: The primary objective of this
      study was to determine whether a single early dose of a diuretic in infants with
      moderate to severe bronchiolitis would improve respiratory distress. Secondary
      objectives examined whether it reduced the use of noninvasive ventilation and
      hospital length of stay. METHODS: Patients diagnosed with clinical bronchiolitis
      were enrolled at a tertiary care, academic children's hospital over a 3-year
      period. This was a double-blind, randomized controlled trial in which subjects
      were randomly assigned to either furosemide or placebo. Respiratory rate and
      oxygen saturation at the time of medication delivery and at 2 and 4 h post
      intervention were recorded, as well as other data. Exact logistic regression was
      used to examine associations. RESULTS: There were 46 subjects enrolled and
      randomized. There was no difference in respiratory rates, measured as a decrease
      of >= 25%, at both 2 and 4 h after intervention between furosemide and placebo
      groups (odds ratios 1.13 and 1.13, respectively). There was also no difference in
      oxygen saturation, intensive care unit admission rate, or hospital length of stay
      between groups. CONCLUSIONS: While theoretically a single dose of a diuretic to
      reduce lung fluid would improve respiratory distress in children with
      bronchiolitis, our randomized controlled medication trial showed no difference in
      outcomes. ClinicalTrials.gov ID: NCT02469597.

PMID- 29174755
TI  - Cerebral plasticity after contralateral cervical nerve transfer in human by
      longitudinal PET evaluation.
AB  - OBJECT: The treatment of brachial plexus avulsion injury remains a challenging
      problem. Admittedly, central nervous mechanisms play a significant role in the
      motor recovery of the paralyzed hand after peripheral nerve surgery. The present
      study aimed at investigating the relationship between cerebral reorganization and
      motor recovery after a unique peripheral crossing nerve transfer surgery in
      brachial plexus injury patients. METHODS: In the present study, two brachial
      plexus avulsion injury patients with were followed up for 4 years after
      contralateral C7 nerve transfer surgery. In the surgery, an intact nerve root
      from the intact limb was transferred to repair the injured nerves. One patient
      showed a good motor recovery in the paralyzed hand while the other showed
      relatively poor outcomes. In the longitudinal follow-up, 9 PET scans of the brain
      were conducted in both patients at regular intervals of every 6 months. A
      correlation analysis between cerebral glucose metabolism and flexion power of the
      paralyzed wrists and fingers was performed to investigate the involvement of
      brain reorganization during the process of motor recovery. RESULTS: The cerebral
      glucose metabolism in the corpus callosum, premotor cortex (Broadmann Area 6) and
      the precuneus were found positively correlated with the motor recovery of the
      paralyzed hand in Patient A (P < .01). Positive correlation between the cerebral
      glucose metabolism and the motor recovery of the paralyze hand was only present
      in the corpus callosum in Patient B (P < .01). CONCLUSION: Corpus callosum,
      premotor cortex and precuneus were related with motor recovery after
      contralateral cervical nerve transfer surgery. The accumulating activation of
      these cortical regions potentially represented the recovery of high-order motor
      networks and may have facilitated the motor recovery.

PMID- 29174756
TI  - Differentiating meningioma grade by imaging features on magnetic resonance
      imaging.
AB  - Atypical meningioma has an aggressive clinical course. Distinguishing atypical
      from benign meningioma preoperatively could affect surgical planning and improve
      treatment outcomes. In this study, we examined whether pre-operative magnetic
      resonance imaging (MRI) features could distinguish between benign and atypical
      meningioma. Imaging factors analyzed included peritumoral edema, the presence of
      a draining vein, tumor necrosis, tumor location and tumor volume. Using
      univariate analysis, the most striking predictor of grade was tumor volume (p <
      .001). When adjusting for the degree of peritumoral edema, volume remained a
      positive predictor of higher histological grade meningioma (p = .042) and was the
      strongest single predictor of higher-grade meningioma in this study. Additional
      imaging features associated with increased risk for atypical pathology in
      univariate analysis included the presence of tumor necrosis (p = .012),
      peritumoral edema (p = .022) and location along the falx and convexity (p =
      .026). Despite statistically significant associations using univariate analysis,
      in multivariate analysis, we found that only presence of peritumoral edema was
      predictive of a higher-grade meningioma. Further multivariate analyses suggests
      that edema, draining vein and necrosis are all positive predictors of tumor
      volume (p < .0001). Overall, these data suggest that radiographic features
      including presence of tumor necrosis, and tumor location along the falx or
      convexity may be predictive of higher-grade meningioma when considered alone.
      However, most strikingly, our data point to tumor volume as the most robust pre
      operative indicator of higher-grade meningioma.

PMID- 29174757
TI  - Anterior transcorporeal tunnel approach for cervical myelopathy guided by CT
      based intraoperative spinal navigation: Technical note.
AB  - Cervical spondylotic myelopathy (CSM) is the most common degenerative disease of
      the spine in elderly patients. Although there are several surgical options for
      the treatment of this disease, minimally invasive techniques for localized
      decompression of the true clinical generator of the patient's disease has
      revolutionized spinal surgery recently. This article presents an alternate
      application of the anterior transcorporeal tunnel approach in combination with
      computed tomography (CT)-based intraoperative navigation in the treatment of
      patients with cervical myelopathy secondary to spondylosis. Three clinical cases
      are used as examples to demonstrate how this procedure can be used to decompress
      a localized target in cervical spondylotic myelopathy. Clinical images of each
      case are shown. Cervical decompression was successfully achieved in all three
      patients, with the improvement of preoperative symptoms. The anterior
      transcorporeal tunnel approach combined with the use of CT-based intraoperative
      spinal navigation may be a feasible minimally invasive procedure for the
      treatment of cervical spondylotic myelopathy in selected cases.

PMID- 29174758
TI  - A Proactive Approach to High Risk Delirium Patients Undergoing Total Joint
      Arthroplasty.
AB  - BACKGROUND: Delirium is a common complication among elderly patients undergoing
      total joint arthroplasty (TJA). Its incidence has been reported from 4% to 53%.
      The Centers for Medicare and Medicaid Services consider delirium following TJA a
      "never-event." The purpose of this study is to evaluate a simple perioperative
      protocol used to identify delirium risk patients and prevent its incidence
      following TJA. METHODS: Our group developed a protocol to identify and prevent
      delirium in patients undergoing TJA. All patients were screened and scored in the
      preoperative assessment, on criteria such as age, history of forgetfulness,
      history of agitation or visual hallucinations, history of falls, history of
      postoperative confusion, and inability to perform higher brain functions.
      Patients were scored on performance in a simple mental examination. The patients
      were classified as low, medium, or high risk. Patients who were identified as
      high risk were enrolled in a delirium avoidance protocol that minimized narcotics
      and emphasized nursing involvement and fluids administration. RESULTS: Five of
      7659 (0.065%) consecutive TJA patients from 2010 to 2015 developed delirium. A
      total of 422 patients were identified as high risk. All 5 patients who suffered
      delirium were within the high risk group. No low or medium risk patients suffered
      a delirium complication. Three (0.039%) patients suffered drug-induced delirium,
      1 (0.013%) had delirium related to alcohol withdrawal, and 1 (0.013%) had
      delirium after a systemic infection. CONCLUSION: This protocol is effective in
      identifying patients at high delirium risk and diminishing the incidence of this
      complication by utilizing a simple screening tool and perioperative protocol.

PMID- 29174759
TI  - Change in Body Mass Index After Total Knee Arthroplasty and Its Influence on
      Functional Outcome.
AB  - BACKGROUND: There is often an assumption by patients that weight loss will occur
      once their knee pain is relieved by total knee arthroplasty (TKA). This study
      aims to evaluate (1) the change in patients' body mass index (BMI) after TKA; (2)
      if postoperative change in BMI influences functional outcome and survival rate of
      TKA; and (3) the predictive factors associated with change in BMI. METHODS: Seven
      thousand seven hundred thirty-three patients who underwent a primary TKA between
      2001 and 2010 were included in this study. Functional outcome scores collected at
      2 years after surgery include the Oxford Knee Score, Knee Society Function Score,
      Knee Society Knee Score, Physical Component Score, and Mental Component Score of
      short form 36. RESULTS: Among these patients, 1067 (14%) had reduction in BMI,
      5045 (65%) maintained their BMI, and 1621 (21%) had gain in BMI. The differences
      in improvement in Oxford Knee Score, Knee Society Function Score, Knee Society
      Knee Score, and Physical Component Score among the 3 groups of patients were less
      than the known minimal clinically important difference of these scores. The 10
      year survival rate of TKA was not influenced by patients' change in BMI after
      surgery (P = .435). Obese class I, II, and III patients were more likely to
      reduce their BMI after TKA than those with normal preoperative BMI (P = .002, P =
      .012, and P = .004, respectively), while older patients were less likely to have
      gain in BMI after surgery (P = .001). CONCLUSION: A change in BMI after TKA did
      not influence the functional outcome clinically or the survival rate of the TKA
      implant.

PMID- 29174760
TI  - Increased Serum Ion Levels After Ceramic-on-Metal Bearing Total Hip Arthroplasty:
      Influence of an Asian Lifestyle.
AB  - BACKGROUND: Recent clinical studies have suggested that systemic metal ion levels
      are significantly elevated at midterm follow-up in patients with ceramic-on-metal
      (COM) bearing. However, it is not clear whether there is a correlation between
      patient-related factors including the lifestyle and elevated levels of serum
      metal ions following COM total hip arthroplasty (THA). METHODS: Serum metal
      levels were measured in 201 patients (234 hips) including 121 COM patients (140
      hips) and 80 non-COM patients (94 hips). The Harris Hip Score, University of
      California, Los Angeles activity scale score, and Western Ontario and McMaster
      Universities Osteoarthritis Index score were measured and radiographs were
      obtained for the analysis. RESULTS: Significantly higher levels of cobalt (Co)
      and chromium (Cr) were detected in the serum of the COM THA group (Co: 1.86 +/-
      4.0 MUg/L; Cr: 1.81 +/- 2.87 MUg/L) than those of the non-COM THA group (Co: 0.27
      +/- 0.14 MUg/L; Cr: 0.19 +/- 0.25 MUg/L; P < .001). The serum metal levels of
      patients who achieved the squatting position and the kneeling position were
      significantly higher than those of patients who could not squat (Co: P = .033;
      Cr: P = .074) and kneel (Co: P = .049; Cr: P = .031). The metal ion levels of the
      COM THA group correlated with the total range of motion (Co: P = .0293; Cr: P =
      .0399). CONCLUSION: Patients who underwent a 36-mm COM THA showed high serum
      metal levels although good clinical outcomes at the midterm follow-up. We found
      that COM THA patients who were capable of greater range of motion, squatting, and
      kneeling are at risk of metal ion-related problems.

PMID- 29174761
TI  - Vancomycin Povidone-Iodine Protocol Improves Survivorship of Periprosthetic Joint
      Infection Treated With Irrigation and Debridement.
AB  - BACKGROUND: Irrigation and debridement with modular component and liner exchange
      (IDLE) is a low morbidity procedure for treatment of periprosthetic joint
      infection (PJI) with reported failure rates exceeding 50%. Dilute povidone-iodine
      lavage has been shown to be safe and effective in decreasing acute PJI in primary
      total joint arthroplasty. Vancomycin powder has also shown to be effective in
      preventing infection in spine surgery. We hypothesize that a vancomycin povidone
      iodine protocol (VIP) used in conjunction with IDLE can increase infection-free
      survivorship after acute PJI. METHODS: This is a single institution retrospective
      review of all PJIs treated with IDLE and VIP since March 2014. A consecutive
      matched control group of patients treated with IDLE for PJI for 2 years prior to
      March 2014 was also included for analysis. Primary outcome was failure, defined
      as return to operating room for an infection-related problem. Secondary outcome
      was chronic suppression with antibiotics at final follow-up. Minimum follow-up
      was 1 year. RESULTS: A total of 36 patients in the VIP group and 38 patients in
      control group were identified. In the VIP group, 16.7% (6/36) failed at final
      follow-up compared to 37% failure rate (14/38) in the control group (P < .05).
      Three patients in the VIP group were on chronic antibiotic suppression at final
      follow-up. There were no medical complications secondary to the VIP. CONCLUSIONS:
      The VIP group demonstrated a significant reduction in reinfection and failure
      rate following IDLE. The authors believe that a VIP is an effective adjunct for
      treating PJI with irrigation and debridement.

PMID- 29174762
TI  - Efficacy of Intravenous Acetaminophen for Postoperative Analgesia in Primary
      Total Knee Arthroplasty.
AB  - BACKGROUND: The use of intravenous acetaminophen has seen recent enthusiasm as
      one component of a multimodal approach to pain management. However, there is a
      lack of literature examining the efficacy of intravenous acetaminophen for pain
      control in total joint arthroplasty. The purpose of this study was to evaluate
      the efficacy of intravenous acetaminophen following primary total knee
      arthroplasty. METHODS: This is a retrospective review of 38 patients undergoing
      primary total knee arthroplasty by a single surgeon at one institution. Twenty
      five patients received 1 gram of intravenous acetaminophen every 6 hours for 24
      hours postoperatively. Thirteen patients received no additional intervention.
      Exclusion criteria were bilateral or concomitant procedures, allergy to
      medications included in the standard postoperative protocol, neuropathy or
      sensory disturbances, history of opioid dependence or abuse, deviations from
      protocol, revision procedures, and incomplete data. Primary outcomes were change
      in patient-reported visual analog scale (VAS) pain score, overall opioid
      consumption measured in morphine milligram equivalents, and hospital length of
      stay. RESULTS: We found no difference in length of stay, at 3.3 days in the
      control group and 2.9 days in the intervention group. There was a significant
      difference in VAS score between 16 and 24 hours. There was a statistically
      significant decrease in overall opioid consumption in the intravenous
      acetaminophen group 37.6 vs 18.6 morphine milligram equivalents. CONCLUSION:
      Intravenous acetaminophen is effective in significantly reducing opioid
      requirements in the first 24 hours following primary total knee arthroplasty.
      Additionally, there is a clinically significant decrease in VAS pain scores in
      patients receiving this intervention.

PMID- 29174763
TI  - Publication Rates in Podium and Poster Presentations at the 2012-2014 American
      Association of Hip and Knee Surgeons Annual Meetings.
AB  - BACKGROUND: Subspecialty conferences are an important forum for disseminating the
      latest research relevant to clinical practice. The purpose of this study was to
      identify publication rates in podium and poster abstracts for the American
      Association of Hip and Knee Surgeons (AAHKS) Annual Meeting and to identify the
      most common journals of publication and the reasons for nonpublication. METHODS:
      Six hundred ten accepted abstracts (182 podium presentations, 428 posters) from
      the 2012-2014 AAHKS meetings were searched using Google, Google Scholar, and
      PubMed. If an abstract could not be found after efforts by multiple searchers,
      the first author was emailed to determine where the research was published or why
      it was not published. For articles that were published, the journal, time to
      publication, and journal impact factor were noted. RESULTS: The overall rate of
      publication was 71% (436/610). Podium presentations (164/182, 90%) were published
      at a higher rate than posters (271/428, 63%). The most common journal of
      publication was the Journal of Arthroplasty (218/436, 50%), followed by Clinical
      Orthopaedics and Related Research (77/436, 18%) and The Journal of Bone and Joint
      Surgery (40/436, 9%). Average time to publication was 14.5 months (range, -4 to
      44 months) from the date of the conference in which it was presented. CONCLUSION:
      Presentations at the AAHKS annual meeting have an impressive rate of publication.
      The research presented at the meeting is impactful and high quality, warranting
      consideration for future publication.

PMID- 29174764
TI  - Evidence that reduced gray matter volume in psychotic disorder is associated with
      exposure to environmental risk factors.
AB  - The aim of this study was to examine whether cannabis use, childhood trauma and
      urban upbringing are associated with total gray matter volume (GMV) in
      individuals with (risk for) psychotic disorder and whether this is sex-specific.
      T1-weighted MRI scans were acquired from 89 patients with a psychotic disorder,
      95 healthy siblings of patients with psychotic disorder and 87 controls.
      Multilevel random regression analyses were used to examine main effects and
      interactions between group, sex and environmental factors in models of GMV. The
      three-way interaction between group, sex and cannabis (chi2 =12.43, p<0.01), as
      well as developmental urbanicity (chi2 = 6.29, p = 0.01) were significant,
      indicating that cannabis use and developmental urbanicity were associated with
      lower GMV in the male patient group (cannabis: B= -32.54, p < 0.01; developmental
      urbanicity: B= -10.23, p=0.03). For childhood trauma, the two-way interaction
      with group was significant (chi2 = 5.74, p = 0.02), indicating that childhood
      trauma was associated with reduced GMV in the patient group (B=-9.79, p=0.01).
      The findings suggest that reduction of GMV in psychotic disorder may be the
      outcome of differential sensitivity to environmental risks, particularly in male
      patients.

PMID- 29174766
TI  - Brain choline in major depression: A review of the literature.
AB  - The focus of this review is to provide a synthesis of the current literature on
      the role of brain choline, as measured by proton magnetic resonance spectroscopy
      (1H-MRS), in major depressive disorder (MDD). The most recent 1H-MRS literature
      review took place over 10 years ago and, reflecting the high level of research on
      this topic, much has been learned since then. Higher brain choline levels have
      been linked to an increase in depression, and a cholinergic model for MDD
      development has been postulated. However, current 1H-MRS studies have been
      inconclusive regarding the role of choline in depression. Data from eighty-six
      peer-reviewed studies were analyzed for a random-effects model meta-analysis. Two
      significant findings are reported. Papers that did not report segmentation had a
      significant, moderate effect size. Higher choline concentrations in the frontal
      lobe were found in depressed patients, both in those who responded to treatment
      and those who did not, after treatment with psychiatric medication, repetitive
      transcranial magnetic stimulation, or electroconvulsive therapy. Findings from
      this review may add to existing information regarding the role of brain choline
      in MDD. This may provide a future target for treatment and drug development. It
      also may serve as a biomarker for treatment progress.

PMID- 29174765
TI  - Attention training modulates resting-state neurophysiological abnormalities in
      posttraumatic stress disorder.
AB  - Recent research indicates the relative benefits of computerized attention control
      treatment (ACT) and attention bias modification treatment (ABMT) for
      posttraumatic stress disorder (PTSD); however, neural changes underlying these
      therapeutic effects remain unknown. This study examines how these two types of
      attention training modulate neurological dysfunction in veterans with PTSD. A
      community sample of 46 combat veterans with PTSD participated in a randomized
      double-blinded clinical trial of ACT versus ABMT and 32 of those veterans also
      agreed to undergo resting-state magnetoencephalography (MEG) recordings. Twenty
      four veterans completed psychological and MEG assessments at pre- and post
      training to evaluate treatment effects. MEG data were imaged using an advanced
      Bayesian reconstruction method and examined using statistical parametric mapping.
      In this report, we focus on the neural correlates and the differential treatment
      effects observed using MEG; the results of the full clinical trial have been
      described elsewhere. Our results indicated that ACT modulated occipital and ABMT
      modulated medial temporal activity more strongly than the comparative treatment.
      PTSD symptoms decreased significantly from pre- to post-test. These initial
      neurophysiological outcome data suggest that ACT modulates visual pathways, while
      ABMT modulates threat-processing regions, but that both are associated with
      normalizing aberrant neural activity in veterans with PTSD.

PMID- 29174767
TI  - Sorcin ablation plus beta-adrenergic stimulation generate an arrhythmogenic
      substrate in mouse ventricular myocytes.
AB  - Sorcin, a penta-EF hand Ca2+-binding protein expressed in cardiomyocytes, is
      known to interact with ryanodine receptors and other Ca2+ regulatory proteins. To
      investigate sorcin's influence on cardiac excitation-contraction coupling and its
      role in the development of cardiac malfunctions, we generated a sorcin knockout
      (KO) mouse model. Sorcin KO mice presented ventricular arrhythmia and sudden
      death when challenged by acute stress induced by isoproterenol plus caffeine.
      Chronic stress, which was induced by transverse aortic constriction,
      significantly decreased the survival rate of sorcin KO mice. Under isoproterenol
      stimulation, spontaneous Ca2+ release events were frequently observed in sorcin
      KO cardiomyocytes. Sorcin KO hearts of adult, but not young mice developed
      overexpression of L-type Ca2+ channel and Na+-Ca2+ exchanger, which enhanced ICa
      and INCX. Consequently, spontaneous Ca2+ release events in sorcin KO
      cardiomyocytes were more likely to induce arrhythmogenic delayed
      afterdepolarizations. Our study demonstrates sorcin deficiency may trigger
      cardiac ventricular arrhythmias due to Ca2+ disturbances, and evidences the
      critical role of sorcin in maintaining Ca2+ homeostasis, especially during the
      adrenergic response of the heart.

PMID- 29174768
TI  - Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development.
AB  - TBX5 plays a critical role in heart and forelimb development. Mutations in TBX5
      cause Holt-Oram syndrome, an autosomal dominant condition that affects the
      formation of the heart and upper-limb. Several studies have provided significant
      insight into the role of TBX5 in cardiogenesis; however, how TBX5 activity is
      regulated by other factors is still unknown. Here we report that histone
      acetyltransferases KAT2A and KAT2B associate with TBX5 and acetylate it at
      Lys339. Acetylation potentiates its transcriptional activity and is required for
      nuclear retention. Morpholino-mediated knockdown of kat2a and kat2b transcripts
      in zebrafish severely perturb heart and limb development, mirroring the tbx5a
      knockdown phenotype. The phenotypes found in MO-injected embryos were also
      observed when we introduced mutations in the kat2a or kat2b genes using the
      CRISPR-Cas system. These studies highlight the importance of KAT2A and KAT2B
      modulation of TBX5 and their impact on heart and limb development.

PMID- 29174769
TI  - Variation in training and use of the focused assessment with sonography in trauma
      (FAST).
AB  - BACKGROUND: Training in ultrasound is variable among residents and practicing
      traumatologists. Focused Assessment with Sonography in Trauma (FAST) may be
      underused in non-urbanized areas, possibly due to lack of training. METHODS:
      State trauma registry data from January 2014-June 2016 were reviewed for FAST
      results. Trauma practitioners were surveyed querying training, confidence, and
      obstacles to performing FAST. RESULTS: 12,855 records revealed highest FAST use
      at the urban Level II center (39%, p < 0.0001). Despite similar injury patterns,
      non-urban/Level III centers' frequency of FAST was only 1-28%. 39 practitioners
      were surveyed, those with training (54%) were more likely to use FAST (p < 0.05).
      61% of practitioners outside the Level II center cited lack of confidence in
      their ability to perform FAST as the primary reason for omitting the exam.
      CONCLUSIONS: FAST is relatively underused in non-urbanized areas of the state.
      Lack of confidence in ability to perform FAST was cited as the primary barrier.

PMID- 29174770
TI  - Can parathyroid hyperplasia be predicted preoperatively?
AB  - INTRODUCTION: The purpose of this study was to determine if there are clinical
      features that raise suspicion for parathyroid hyperplasia. MATERIALS & METHODS:
      We retrospectively reviewed patients with primary hyperparathyroidism who
      underwent parathyroidectomy from 1991 to 2017, analyzing demographics, calcium
      and PTH, and localizing studies for patients with hyperplasia and single adenoma.
      RESULTS: 549 patients underwent parathyroidectomy: 464 (85%) with adenoma, 44
      (8%) with double adenoma, 38 (7%) with hyperplasia, and 3 (1%) with cancer.
      Compared to patients with a single adenoma, patients with hyperplasia were more
      likely to have negative sestamibi, ultrasound or both exams (92% vs 6%, p <
      0.001; 96% vs 4%, p < 0.001; and 91% vs 2%, p < 0.001) and lower gland weights
      (619 +/- 1067 mg vs. 1466 +/- 1899 mg, p < 0.001). CONCLUSION: Parathyroid
      hyperplasia should be suspected in patients with lower gland weights and negative
      imaging.

PMID- 29174771
TI  - Surgery residents recognized less frequently over time by medical students: A
      twelve year study of the Arnold P. Gold Humanism and Excellence in Teaching
      Award.
AB  - BACKGROUND: There is a decreasing institutional percentage of surgical resident
      recipients of The Arnold P. Gold Humanism and Excellence in Teaching Award over
      time. The hypothesis was that this trend was a national phenomenon. METHODS: This
      was a retrospective study from 2004 - 2015, utilizing data from the Arnold P.
      Gold Foundation. Multiple regression was performed using the estimated ratio of
      eligible surgical to non-surgical residents and the year as explanatory
      variables, utilizing an alpha = 0.05. RESULTS: The percentage of surgical award
      winners was lower in the second study half compared to the first half (40.2% vs.
      47.2%) (p = 0.02). Multiple regression showed that when controlling for the
      number of eligible residents, the number of resident awardees decreased over time
      (p = 0.01). CONCLUSION: There is a clear national trend that surgical residents
      are receiving the Arnold P. Gold Humanism and Excellence in Teaching Award less
      over time.

PMID- 29174772
TI  - Leaders by example: Best practices and advice on establishing a state-of-the art
      surgical simulation center that optimizes available resources.
AB  - BACKGROUND: The role of simulation-based education continues to expand
      exponentially. To excel in this environment as a surgical simulation leader
      requires unique knowledge, skills, and abilities that are different from those
      used in traditional clinically-based education. METHODS: Leaders in surgical
      simulation were invited to participate as discussants in a pre-conference course
      offered by the Association for Surgical Education. Highlights from their
      discussions were recorded. RESULTS: Recommendations were provided on topics such
      as building a simulation team, preparing for accreditation requirements, what to
      ask for during early stages of development, identifying tools and resources
      needed to meet educational goals, expanding surgical simulation programming, and
      building educational curricula. CONCLUSION: These recommendations provide new
      leaders in simulation with a unique combination of up-to-date best practices in
      simulation-based education, as well as valuable advice gained from lessons
      learned from the personal experiences of national leaders in the field of
      surgical simulation and education.

PMID- 29174773
TI  - The diagnosis and staging of pancreatic cancer: A comparison of endoscopic
      ultrasound and computed tomography with pancreas protocol.
AB  - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death
      in United States. We compared Computed Tomography (CT) with pancreas protocol and
      Endoscopic Ultrasound (EUS) in terms of mass detection, mass size, vascular
      involvement and lymph node involvement. METHODS: We retrospectively evaluated 93
      patients. Concordance between CT and EUS, and accuracy of CT and EUS were
      assessed using a retrospective chart review and statistical analysis. RESULTS: CT
      and EUS agreed on mass detection in 88% of the cases and mass size in 67% of the
      cases. They agreed in 74% of cases about the presence or absence of vascular
      involvement and 82% in lymph node involvement. Cohen's kappa indicated that the
      concordance between two tests was moderately reliable. CONCLUSION: CT and EUS
      agree moderately well in identifying characteristics of pancreatic masses, but
      discrepancies between the two modalities are common, particularly with respect to
      involvement of specific blood vessels and lymph nodes. Clinicians should use
      caution in relying on a single modality to make decisions.

PMID- 29174774
TI  - Do not break up the surgical team! Familiarity and expertise affect operative
      time in complex surgery.
AB  - BACKGROUND: The effects of replacing a surgeon's familiar, experienced certified
      surgical assistant (CSA) on perioperative outcomes in complex surgery were
      investigated. METHODS: An interrupted time series of totally laparoscopic
      pancreatoduodenectomies performed by a single surgeon was retrospectively
      studied. Segmented regression analysis estimated replacement effects on estimated
      blood loss (EBL) and operative time. RESULTS: The cohort was composed of the last
      100 cases with the familiar CSA and the first 100 cases with the replacement CSA.
      Study groups were similar. Unadjusted segmented regression of operative time and
      EBL predicted replacement effects of 70 min (95%CI, 18-122; p = 0.008) and 114 cc
      (95%CI, -93-320; p = 0.3), respectively. Adjusted regression predicted
      replacement effects of 40 min (95%CI, 0.9-78; p = 0.04) and 27 cc (95%CI, -156
      210; p = 0.3). CONCLUSIONS: The replacement of a familiar, experienced CSA was
      associated with longer operative times. Despite confinement to a single surgeon
      and procedure, these results suggest what all surgeons know: excellent help is
      priceless.

PMID- 29174775
TI  - Novel Automated Suturing Technology for Minimally Invasive Aortic Valve
      Replacements.
AB  - PURPOSE: Annular suture placement during minimally invasive right anterior
      thoracotomy aortic valve replacements (MI-AVR) can be challenging. We present the
      early clinical experience with novel automated suturing technology that may
      reduce the technical difficulty of this operation. DESCRIPTION: The technology
      presented involves an automated articulating suturing device that simultaneously
      drives dual-curved needles through the aortic annulus to place a pledgeted
      horizontal mattress suture remotely; a second device with 2 straight needles
      places suture through the sewing cuff of a prosthetic heart valve. EVALUATION:
      Automated annular suturing was used in five MI-AVR procedures, which were
      successfully completed, with no paravalvular leaks detected and a mean aortic
      valve gradient of 6.4 mm Hg postprocedure. Mean aortic cross-clamp and
      cardiopulmonary bypass times were 100 and 134 minutes, respectively. All 5
      patients were successfully discharged home, with a mean intensive care unit and
      total length of stay of 2 and 7 days, respectively. CONCLUSIONS: Automated
      suturing during MI-AVRs is feasible and may reduce the technical challenge of
      this operation. Further research is necessary to determine its effect on patient
      outcomes.

PMID- 29174776
TI  - Management of Surge in Extracorporeal Membrane Oxygenation Transport.
AB  - BACKGROUND: Transporting patients receiving extracorporeal membrane oxygenation
      (ECMO) support is safe and reliable with a dedicated program and established
      management protocols. As our program has grown, our teams have had to adapt to
      manage surges in transport volume while maintaining patient safety. We assessed
      the outcomes at peak use of our ECMO transport services during surges. METHODS:
      We conducted a single-center retrospective review of all patients transported to
      our institution while supported with ECMO from September 2008 to September 2016.
      Survival to discharge was the primary outcome. Surge patients were defined as
      those transported during months with at least 8 transports or patients
      transported within 24 hours of another patient in nonsurge months. RESULTS: From
      2008 to 2016, 222 patients were transported to our institution while supported
      with ECMO. Baseline characteristics and indices of disease severity were
      comparable between surge and nonsurge patients. Of the 84 patients transported
      during surges, 59 surge patients (70%) survived to hospital discharge vs 86 (63%)
      of nonsurge patients (p = 0.31). Multivariable logistic regression showed that
      age and APACHE II (Acute Physiology and Chronic Health Evaluation) severity index
      score were predictors of in-hospital death (p < 0.05), but transportation during
      a surge was not (odds ratio, 0.91; 95% confidence interval, 0.46 to 1.80; p =
      0.79). CONCLUSIONS: Patient safety and clinical outcomes can be maintained during
      surges in ECMO transport volume if the ECMO program has developed plans for
      handling transient increases in volume and considers staff fatigue and burnout.
      Standardizing interhospital communication, patient selection, and management
      protocols are critical to maintaining quality of care.

PMID- 29174777
TI  - Cardiac Surgery Outcomes in Abdominal Solid Organ Transplant Recipients.
AB  - BACKGROUND: Cardiovascular disease is a cause of morbidity and mortality in organ
      transplant recipients. Cardiac surgery after organ transplantation is not
      uncommon in this population. We evaluated 30-day outcomes and long-term survival
      of abdominal transplant recipients undergoing cardiac surgery at our institution.
      METHODS: In all, 138 patients with previous kidney, kidney-pancreas, and liver
      transplants underwent cardiac surgery from 2000 to 2016. Propensity score (ratio
      1:3) matched 115 abdominal transplant with 345 patients undergoing cardiac
      surgery without a history of abdominal transplant. They were matched for type and
      year of cardiac surgery, age, sex, body mass index, history of diabetes mellitus,
      and creatinine level before cardiac surgery. RESULTS: Median time from abdominal
      transplant to cardiac surgery was 7 years (interquartile range, 3 to 12 years).
      Perioperative variables, including surgery and cardiopulmonary bypass time,
      aortic cross-clamp and intubation time, and intensive care unit stay did not
      differ between the groups. Hospital length of stay and rate of 30-day hospital
      readmissions did not differ between the groups. Patients with abdominal
      transplants had more strokes (4% versus 0.6%; p = 0.005) within 30 days after
      surgery. There were no differences in renal failure, bleeding, site infections,
      atrial fibrillation, and pneumonia between the groups. Five patients (4%) died
      within 30 days after surgery in the abdominal transplant group (4 kidneys, 1
      liver, 0 kidney-pancreas), and 7 patients (2%) died in the nontransplanted group
      (p = 0.24). CONCLUSIONS: Previous history of abdominal transplant is associated
      with an increased 30-day incidence of stroke after cardiac surgery. Abdominal
      transplant does not affect 30-day mortality after cardiac surgery, whereas long
      term survival is significantly reduced. Regular patient follow-up and prevention
      and early treatment of postoperative complications are key to patient survival.

PMID- 29174778
TI  - Association of Donor Tricuspid Valve Repair With Outcomes After Cardiac
      Transplantation.
AB  - BACKGROUND: Tricuspid regurgitation after cardiac transplantation is associated
      with worse clinical outcomes. This study sought to determine the association of
      donor tricuspid valve repair (dTVR) with outcomes after cardiac transplantation.
      METHODS: Patients who underwent cardiac transplantation between January 20, 2002,
      and December 31, 2016, were included. Multivariable Cox regression modeling was
      performed to determine the association between dTVR and the composite outcome of
      death, posttransplant TVR, kidney transplant after cardiac transplant, or chronic
      dialysis, and included propensity scoring to control for baseline differences in
      likelihood of undergoing dTVR. RESULTS: The analysis included 330 patients, with
      173 (52.4%) undergoing dTVR. dTVR performance varied by surgeon and also
      increased over time, with 71 (83.5%) performed during January 1, 2011, to
      November 30, 2013. Transplant year and surgeon were significantly associated with
      the baseline likelihood of undergoing dTVR. Although fewer composite outcomes
      occurred in the dTVR vs no dTVR group (39 [22.5%] vs 56 [36.4%], p = 0.006), dTVR
      was not significantly associated with the composite outcome in multivariable
      modeling. Lower risk for the composite outcome was associated with greater number
      of biopsies during the first posttransplant year, whereas higher risk was
      associated with more high-grade biopsy specimens and higher creatinine.
      CONCLUSIONS: There was no significant benefit or harm with regards to the
      composite of death, posttransplant TVR, or dialysis associated with dTVR.

PMID- 29174779
TI  - External Suction and Fluid Output in Chest Drains After Lobectomy: A Randomized
      Clinical Trial.
AB  - BACKGROUND: Even when air leakage has ceased completely after lobectomy, chest
      drains are often not removed because of high fluid output. Accepted thresholds
      for removal vary between institutions but typically range between 200 and 500
      mL/d. There is little knowledge whether external suction influences the amount of
      fluid. METHODS: We randomly assigned (1:1) 106 patients who underwent lobectomy
      to either low (-5 cm H2O) or high (-20 cm H2O) external suction using an
      electronic chest drainage system. Only one chest drain was allowed, and we used
      strict algorithms for chest drain removal, which was delegated to staff nurses:
      air leakage less than 20 mL/min for 6 hours regardless of fluid output, provided
      it was serous. The primary end point was fluid output after 24 and 48 hours.
      RESULTS: Mean fluid output was significantly higher with high suction after both
      24 (338 +/- 265 mL versus 523 +/- 215 mL) and 48 hours (616 +/- 366 mL versus
      1067 +/- 387 mL (p < 0.001). Repeated measure analysis (mixed model) demonstrated
      that in addition to suction level the surgical approach (video-assisted
      thoracoscopic surgery/thoracotomy, p = 0.04) and affected lobe (upper/lower, p =
      0.001) were significant predictors of fluid production. CONCLUSIONS: Increased
      suction levels lead to increased fluid output. Thoracotomy and lower lobectomy
      are associated with increased fluid output in chest drains, which should be taken
      into consideration if algorithms for chest drain removal include an upper limit
      of fluid output.

PMID- 29174780
TI  - Hospitalization Costs After Surgery in High-Risk Patients With Early Stage Lung
      Cancer.
AB  - BACKGROUND: We previously reported that early stage lung cancer patients who are
      considered high risk for surgery can undergo resection with favorable
      perioperative results and long-term mortality. To further elucidate the role of
      surgical resection in this patient cohort, this study evaluated the length of
      stay and total hospitalization cost among patients classified as standard or high
      risk with early stage lung cancer who underwent pulmonary resection. METHODS: A
      total of 490 patients from our institutional Society of Thoracic Surgeons data
      from 2009 to 2013 underwent resection for clinical stage I lung cancer. High-risk
      patients were identified by American College of Surgeons Oncology Group z4032
      z4099 criteria. Demographics, length of stay, and hospitalization cost between
      high-risk and standard-risk patients undergoing lobectomy and sublobar resection
      were compared. Univariate analysis was performed using the chi-square test or
      Fisher's exact test. Multivariate analysis was performed using a linear
      regressions model. RESULTS: A total of 180 (37%) of patients were classified as
      high risk. These patients were older (70 years of age vs. 65 years of age; p <
      0.0001), had worse forced expiratory volume in 1 second (57% vs. 85%; p <
      0.0001), and had worse diffusion capacity of carbon dioxide (47% vs. 77%; p <
      0.0001). The baseline cost and length of stay was represented by a thoracoscopic
      wedge resection in a standard-risk patient. A larger extent of resection,
      thoracotomy, or high-risk classification increased the cost and length of stay.
      CONCLUSIONS: Our previous study showed that good clinical outcomes after surgery
      for early stage lung cancer can be achieved in patients classified as high risk.
      In this study, although surgery in high-risk patients led to slightly increased
      costs, these costs seemed negligible when viewed along with the patients'
      excellent short-term and long-term results. This study suggests that surgical
      resection on high-risk patients with early stage lung cancer is associated with
      acceptable hospital lengths of stay and overall cost when compared with standard
      risk patients.

PMID- 29174781
TI  - Utilization of Veno-Arterial Extracorporeal Membrane Oxygenation for Massive
      Pulmonary Embolism.
AB  - BACKGROUND: The management of massive pulmonary embolism remains challenging,
      with a considerable mortality rate. Although veno-arterial extracorporeal
      membrane oxygenation (VA-ECMO) for massive pulmonary embolism has been reported,
      its use as salvage therapy has been associated with poor outcomes. We reviewed
      our experience utilizing an aggressive, protocolized approach of VA-ECMO to
      triage, optimize, and treat these patients. METHODS: All patients with a massive
      pulmonary embolism who were placed on VA-ECMO, as an initial intervention
      determined by protocol, were retrospectively reviewed. ECMO support was continued
      until organ optimization was achieved or neurologic status was determined. At
      that time, if the thrombus burden resolved, decannulation was performed. If
      substantial clot burden was still present with evidence of right ventricular (RV)
      strain, operative therapy was undertaken. RESULTS: Twenty patients were
      identified. Before cannulation, all patients had an RV-to-left ventricular ratio
      greater than 1.0 and severe RV dysfunction. The median duration of ECMO support
      was 5.1 days, with significant improvement in end-organ function. Ultimately, 40%
      received anticoagulation alone, 5% underwent catheter-directed therapy, and 55%
      underwent surgical pulmonary embolectomy. Care was withdrawn in 1 patient with a
      prolonged pre-cannulation cardiac arrest after confirmation of neurologic death.
      In-hospital and 90-day survival was 95%. At discharge, 18 of 19 patients had
      normal RV function, and 1 patient, who received catheter-directed therapy, had
      mild dysfunction. CONCLUSIONS: VA-ECMO appears to be an effective tool to
      optimize end-organ function as a bridge to recovery or intervention, with
      excellent outcomes. This approach may allow clinicians to better triage patients
      with massive pulmonary embolism to the appropriate therapy on the basis of
      recovery of RV function, residual thrombus burden, operative risk, and neurologic
      status.

PMID- 29174782
TI  - Pericardial Blood as a Trigger for Postoperative Atrial Fibrillation After
      Cardiac Surgery.
AB  - BACKGROUND: Prevention strategies have long been sought to reduce the incidence
      and burden of postoperative atrial fibrillation (POAF) after heart surgery.
      However, none has emerged as a dominant and widely applicable prophylactic
      measure. The purpose of this review is to consider the biological mechanisms by
      which shed mediastinal blood leads to oxidation and inflammation within the
      postoperative pericardial environment and how this might trigger POAF in
      susceptible persons, as well as how it could represent a new target for
      prevention of POAF. METHODS: We conducted a structured research of literature
      using PubMed and MEDLINE databases to May 2016. Biomolecular and clinical
      articles focused on assessing the contribution of pericardial blood, or the
      resulting inflammation within the pericardial space and its potential role in
      triggering POAF, were included in this review. RESULTS: Evidence suggests that
      shed mediastinal blood through breakdown products, activation of coagulation
      cascade, and oxidative burst contributes to a highly pro-oxidant and
      proinflammatory milieu found within the pericardial space that can trigger
      postoperative atrial fibrillation in susceptible persons. The extent of this
      reaction could be blunted by reducing the exposition of pericardium to blood
      either through posterior pericardiotomy or improved chest drainage. CONCLUSIONS:
      Shed mediastinal blood undergoing transformation within the pericardium appears
      to be an important contributing factor to POAF. Strategies to prevent shed
      mediastinal blood from pooling around the heart might be considered in developing
      future paradigms for prevention of POAF.

PMID- 29174783
TI  - Improving Results of Surgery for Ebstein Anomaly: Where Are We After 235 Cone
      Repairs?
AB  - BACKGROUND: Ebstein anomaly has heterogeneous anatomy and numerous operative
      techniques are described. Cone repair provides a near anatomic tricuspid valve
      repair. The purpose of this study was to examine our experience with cone repair.
      METHODS: Cone repair was performed in 235 consecutive patients with Ebstein
      anomaly, 134 children (57%) and 101 adults (43%), from June 2007 to October 2015.
      Median age was 15.6 years (range, 6 months to 73 years). Cone repair was the
      first operation in 192 patients (82%), the second in 41 (17%), and the third in 2
      (1%). Previous tricuspid valve repair had been performed in 27 (12%).
      Echocardiograms were obtained preoperatively and at hospital dismissal for all
      patients and for a subgroup of patients at least 6 months after cone repair (n =
      81). RESULTS: Leaflet augmentation was done in 67 patients (28%), Sebening stitch
      in 57 (24.2%), neochordae in 49 (21%), and annuloplasty band in 158 (67%).
      Bidirectional cavopulmonary shunt was performed in 46 patients (20%). There was 1
      early death (0.4%). Early reoperation was required in 14 patients (5.9%); re
      repair was possible in 7 (50%). The majority of early reoperations (11 of 14;
      79%) occurred in the first third of the series. Mean follow-up was 3.5 +/- 2.5
      years. There was sustained reduction in tricuspid regurgitation (p < 0.0001), a
      progressive decline in right ventricle size (p < 0.0001), and late increase in
      right ventricle fractional area change after initial decline (p < 0.0001).
      Freedom from late reoperation was 97.9% at 6 years. CONCLUSIONS: Cone repair is
      safe, and the learning curve is significant. Sustained reduction in tricuspid
      regurgitation and favorable changes in the right ventricle at follow-up suggest
      that cone repair has an advantageous impact on right ventricular remodeling.

PMID- 29174784
TI  - Colonization With Multiresistant Bacteria: Impact on Ventricular Assist Device
      Patients.
AB  - BACKGROUND: Although the effect of infections with multidrug-resistant bacteria
      (MDRB) in left ventricular assist device (LVAD) recipients is well characterized,
      the influence of perioperative colonization on the development of infections in
      this patient cohort remains unknown. The study evaluated the effect of MDRB
      colonization on patient outcomes after LVAD implantation. METHODS: We
      retrospectively analyzed the microbiological screening studies of nasal, throat,
      wound, and rectal swabs in 82 consecutive patients who received an LVAD at our
      center between 2010 and 2015. Four categories of MDRB were determined:
      methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus,
      and Gram-negative bacterium resistant to three or four of four predefined
      pharmacologic categories of antibiotics. We also compared the long-term outcome
      of patients with and without colonization. RESULTS: There were 28 patients
      (34.1%) diagnosed as being colonized with at least 1 species of an MDRB. MDRB
      colonization was associated with the occurrence of fatal infections from any
      pathogen (MDRB positive, 63.2%; MDRB negative, 34.4%; p = 0.04) and fatal MDRB
      specific infections (MDRB positive, 31.6%; MDRB negative, 6.3%; p = 0.04),
      significantly longer intensive care unit stay (p < 0.0001), and longer cumulative
      hospital stay (p = 0.04). CONCLUSIONS: Our study demonstrates that the
      colonization with MDRB is a highly prevalent risk factor for infection-associated
      death in the vulnerable LVAD population. Routine screening for MDRB before and
      after LVAD implantation should be considered to identify high-risk individuals
      and facilitate effective prevention of infectious complications.

PMID- 29174786
TI  - Endothelial Shear Stress of the Saphenous Vein Composite Graft Based on the
      Internal Thoracic Artery.
AB  - BACKGROUND: Endothelial shear stress (ESS) has been suggested as a factor
      affecting atherosclerosis and remodeling of native vessels and bypass conduits.
      We compared ESS levels of internal thoracic artery (ITA) and saphenous vein (SV)
      composite grafts intraoperatively and 1 year after coronary artery bypass
      grafting (CABG). METHODS: Intraoperative ESS was calculated by measuring flow
      volumes and diameters of proximal and distal ITAs and SV conduits in 23 patients
      who received SV Y-composite grafts based on the in situ left ITA. Early (1.2 +/-
      0.5 days) and 1-year (12.9 +/- 1.1 months) postoperative angiograms were
      performed in 23 and 15 patients, respectively. An intragraft Doppler-guidewire
      study for ESS measurement was performed in 6 patients during 1-year angiography.
      RESULTS: Intraoperative diameters of proximal and distal ITAs and SV conduits
      were 2.0 +/- 0.2 mm, 1.8 +/- 0.3 mm, and 3.2 +/- 0.4 mm, respectively. ESS levels
      were significantly different between them (41.0 +/- 21.0, 28.4 +/- 25.2, and 4.3
      +/- 3.0 dyne/cm2, respectively). Proximal and distal ITA diameters increased
      significantly on early angiograms and remained unchanged, but SV diameter
      increased to 3.7 mm (95% confidence interval, 3.5 to 4.0 mm; p < 0.001) on the
      early angiogram and decreased to 2.9 mm (95% confidence interval, 2.7 to 3.2 mm;
      p < 0.001) at 1 year. Significant correlations were found between the initial ESS
      and proportional changes in conduit diameters during postoperative year 1. SV ESS
      increased in all 6 patients at 1 year, with no significant differences in ESS
      levels between the 3 conduits (29.9 +/- 7.9, 28.8 +/- 7.9, and 21.6 +/- 16.3
      dyne/cm2, respectively). CONCLUSIONS: Initial ESS appears to be associated with
      proportional changes in conduit diameters in the first year after CABG. ESS
      values of SV composite grafts were similar to left ITA conduits 1 year after
      CABG.

PMID- 29174787
TI  - Updated Trends in Gallbladder and Other Biliary Tract Cancers Worldwide.

PMID- 29174785
TI  - Determinants of Variation in Pneumonia Rates After Coronary Artery Bypass
      Grafting.
AB  - BACKGROUND: Although conventional wisdom suggests that differences in patient
      risk profiles drive variability in postoperative pneumonia rates after coronary
      artery bypass grafting (CABG), this teaching has yet to be empirically tested. We
      determined to what extent patient risk factors account for hospital variation in
      pneumonia rates. METHODS: We studied 324,085 patients undergoing CABG between
      July 1, 2011, and December 31, 2013, across 998 hospitals using The Society of
      Thoracic Surgeons Adult Cardiac Database. We developed 5 models to estimate our
      incremental ability to explain hospital variation in pneumonia rates. Model 1
      contained patient demographic characteristics and admission status, while Model 2
      added patient risk factors. Model 3 added measures of pulmonary function, Model 4
      added measures of cardiac anatomy and function and medications, and Model 5
      further added measures of intraoperative and postoperative care. RESULTS:
      Although 9,175 patients (2.83%) experienced pneumonia, the median estimated
      distribution of pneumonia rates across hospitals was 2.5% (25th to 75th
      percentile: 1.5% to 4.0%). Wide variability in pneumonia rates was evident, with
      some hospitals having rates more than 6 times higher than others (10th to 90th
      percentile: 1.0% to 6.1%). Among all five models, Model 2 accounted for the most
      variability at 4.24%. In total, 2.05% of hospital variation in pneumonia rates
      was explained collectively by traditional patient factors, leaving 97.95% of
      variation unexplained. CONCLUSIONS: Our findings suggest that patient risk
      profiles only account for a fraction of hospital variation in pneumonia rates;
      enhanced understanding of other contributory factors (eg, processes of care) is
      required to lessen the likelihood of such nosocomial infections.

PMID- 29174788
TI  - Different Cutpoints for Transient Elastography Lead to Different Associations
      With Cirrhosis.

PMID- 29174789
TI  - Simplifying Resect and Discard Strategies for Real-Time Assessment of Diminutive
      Colorectal Polyps.
AB  - BACKGROUND & AIMS: During endoscopy, the resect and discard strategy, if
      performed with high confidence, can be used to determine histologic features of
      diminutive colorectal polyps (5 mm or less). These polyps can then be removed and
      discarded without pathology assessment. However, the complexities of real-time
      optical assessment and follow-up management have provided challenges to
      widespread use of this approach. We aimed to determine the outcomes of simple
      alternative strategies, in which all diminutive polyps can be resected and
      discarded. METHODS: We collected data from 2 previous studies that used narrow
      band imaging to assess polyps, performed at 5 medical centers (1658 patients with
      2285 diminutive polyps; 15 endoscopists). We compared 3 resect and discard
      strategies: the currently used optical strategy, which relies on high confidence
      optical assessment of all diminutive polyps; a location-based strategy that
      classifies all recto-sigmoid diminutive polyps a priori as hyperplastic and all
      polyps proximal to the recto-sigmoid colon a priori as neoplastic; and a
      simplified optical strategy, in which all recto-sigmoid diminutive polyps are
      classified as hyperplastic unless confidently assessed as neoplastic, and all
      polyps proximal to the recto-sigmoid colon are classified as neoplastic unless
      confidently assessed as hyperplastic polyps. The primary outcome was the
      agreement of the surveillance interval calculated for each strategy with the
      surveillance interval determined by pathology analysis. RESULTS: The proportion
      of surveillance intervals that agreed with pathology-based surveillance
      recommendations was slightly higher when the optical strategy was used compared
      to the location-based strategy or simplified optical strategy (94% vs 89% and
      90%, respectively; P < .001). When the 5-10 year recommendations for patients
      with low-risk polyps were applied as a 10-year surveillance interval, all 3
      strategies resulted in surveillance interval agreement compared to pathology
      above 90% (the quality benchmark). Use of the simplified or location-based
      strategy could have avoided pathology analysis for 77% of all polyps, compared to
      59% if the optical strategy was used (P < .001). In addition, a higher proportion
      of patients could receive recommendations immediately after colonoscopy with use
      of the simplified or location based strategy (65%) compared to the optical
      strategy (40%) (P < .001). CONCLUSION: A location-based and a simplified optical
      resect and discard strategy produced surveillance recommendations that were in
      agreement with those from pathology analysis for at least 90% of patients,
      assuming a 10-year surveillance interval for patients with low-risk polyps. These
      strategies could further reduce the number of pathology examinations and provide
      more patients with immediate surveillance recommendations. Optical assessment
      might be reduced or might not be required for resect and discard. Clintrials.gov
      no: NCT01935180 and NCT01288833.

PMID- 29174790
TI  - Towards measuring the semantic capacity of a physical medium demonstrated with
      elementary cellular automata.
AB  - The organic code concept and its operationalization by molecular codes have been
      introduced to study the semiotic nature of living systems. This contribution
      develops further the idea that the semantic capacity of a physical medium can be
      measured by assessing its ability to implement a code as a contingent mapping.
      For demonstration and evaluation, the approach is applied to a formal medium:
      elementary cellular automata (ECA). The semantic capacity is measured by counting
      the number of ways codes can be implemented. Additionally, a link to information
      theory is established by taking multivariate mutual information for quantifying
      contingency. It is shown how ECAs differ in their semantic capacities, how this
      is related to various ECA classifications, and how this depends on how a meaning
      is defined. Interestingly, if the meaning should persist for a certain while, the
      highest semantic capacity is found in CAs with apparently simple behavior, i.e.,
      the fixed-point and two-cycle class. Synergy as a predictor for a CA's ability to
      implement codes can only be used if context implementing codes are common. For
      large context spaces with sparse coding contexts synergy is a weak predictor.
      Concluding, the approach presented here can distinguish CA-like systems with
      respect to their ability to implement contingent mappings. Applying this to
      physical systems appears straight forward and might lead to a novel physical
      property indicating how suitable a physical medium is to implement a semiotic
      system.

PMID- 29174791
TI  - Patient-perceived health service needs in inflammatory arthritis: A systematic
      scoping review.
AB  - BACKGROUND: Care that is patient-centred is more likely to be sustainable and
      associated with improved health outcomes. This approach to care requires an
      understanding of patients' health service needs, yet few studies have directly
      investigated the perceived health service needs of people with inflammatory
      arthritis. OBJECTIVES: To systematically identify the existing literature
      relating to patient perceived health service needs for inflammatory arthritis.
      METHODS: A systematic review of MEDLINE, EMBASE, CINAHL, and PsycINFO was
      conducted (1990-2016). Studies examining patients' perceived needs relating to
      health services for inflammatory arthritis were identified. Descriptive data
      regarding study design and methodology were extracted and risk of bias assessed.
      Findings were collated and categorized thematically. RESULTS: In total, 27 of
      1405 (16 qualitative, 9 quantitative, and 2 mixed-methods) studies were relevant.
      The main areas of perceived need related to (1) Communication: consumers wanted
      clear, empathic communication, and to be involved with decision-making. (2)
      Characteristics of ongoing care: adequate consultation length with continuity and
      timely care were valued. (3) Factors influencing care-seeking included individual
      attitudes, disease severity, finances and family expectations. (4) Allied health
      and complementary and alternative medicines (CAM) were perceived as useful by
      many. The reporting of CAM use to doctors was variable, with several factors
      contributing to under-reporting. CONCLUSIONS: This review identified patients'
      perceived needs for better communication with their health providers, the
      heterogeneity of influences determining when care is sought and preferences
      regarding non-pharmacologic therapies. Aligning patients' perceived needs with
      evidence-based therapy for people with inflammatory arthritis will be important
      in optimizing patient outcomes.

PMID- 29174793
TI  - Footwear interventions for foot pain, function, impairment and disability for
      people with foot and ankle arthritis: A literature review.
AB  - OBJECTIVE: To conduct a literature review on the effectiveness of footwear on
      foot pain, function, impairment and disability for people with foot and ankle
      arthritis. METHODS: A search of the electronic databases Scopus, Medline, CINAHL,
      SportDiscus and the Cochrane Library was undertaken in September 2017. The key
      inclusion criteria were studies reporting on findings of footwear interventions
      for people with arthritis with foot pain, function, impairment and/or disability.
      The Quality Index Tool was used to assess the methodological quality of studies
      included in the qualitative synthesis. The methodological variation of the
      included studies was assessed to determine the suitability of meta-analysis and
      the grading of recommendations, assessment, development and evaluation (GRADE)
      system. Between and within group effect sizes were calculated using Cohen's d.
      RESULTS: 1440 studies were identified for screening with 11 studies included in
      the review. Mean (range) quality scores were 67% (39-96%). The majority of
      studies investigated rheumatoid arthritis (n = 7), but also included gout (n =
      2), and 1st metatarsophalangeal joint osteoarthritis (n = 2). Meta-analysis and
      GRADE assessment were not deemed appropriated based on methodological variation.
      Footwear interventions included off-the-shelf footwear, therapeutic footwear and
      therapeutic footwear with foot orthoses. Key footwear characteristics included
      cushioning and a wide toe box for rheumatoid arthritis; cushioning, midsole
      stability and a rocker-sole for gout; and a rocker-sole for 1st
      metatarsophalangeal joint osteoarthritis. Between group effect sizes for outcomes
      ranged from 0.01 to 1.26. Footwear interventions were associated with reductions
      in foot pain, impairment and disability for people with rheumatoid arthritis.
      Between group differences were more likely to be observed in studies with shorter
      follow-up periods in people with rheumatoid arthritis (12 weeks). Footwear
      interventions improved foot pain, function and disability in people with gout and
      foot pain and function in 1st metatarsophalangeal joint osteoarthritis. Footwear
      interventions were associated with changes to plantar pressure in people with
      rheumatoid arthritis, gout and 1st metatarsophalangeal joint osteoarthritis and
      walking velocity in people with rheumatoid arthritis and gout. CONCLUSION:
      Footwear interventions are associated with reductions in foot pain, impairment
      and disability in people with rheumatoid arthritis, improvements to foot pain,
      function and disability in people with gout and improvements to foot pain and
      function in people with 1st metatarsophalangeal joint osteoarthritis. Footwear
      interventions have been shown to reduce plantar pressure rheumatoid arthritis,
      gout and 1st metatarsophalangeal joint osteoarthritis and improve walking
      velocity in rheumatoid arthritis and gout.

PMID- 29174792
TI  - A randomized, double-blind, placebo-controlled trial of infliximab in refractory
      polymyositis and dermatomyositis.
AB  - OBJECTIVE: To investigate in a pilot study the safety and efficacy of infliximab
      in patients with refractory dermatomyositis (DM) and polymyositis (PM). METHODS:
      A randomized, double-blind, placebo-controlled trial including subjects with
      active DM or PM. Participants had stable doses of immunosuppressive medication
      and prednisone (<=0.5mg/kg/day), and exhibited clinical signs of muscle weakness
      for at least 4 weeks prior to study entry. Participants received infusions of
      either placebo or infliximab 5mg/kg at 0, 2, 6, and 14 weeks in blinded manner.
      The primary outcome was a >=15% manual muscle strength (MMT) improvement at week
      16 compared to week 0. The secondary outcome measures were improvement defined by
      the International Myositis Assessment and Clinical Studies Group (IMACS)
      criteria. At week 16, responders in each arm had the option of either continuing
      the same treatment or changing to the non-responder treatment for that study arm.
      Non-responders in the 5mg/kg infliximab arm were increased to infliximab 7.5mg/kg
      for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received
      infliximab 5mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at
      week 40. RESULTS: Twelve subjects completed the study to week 16. Six of the 12
      subjects received infliximab treatment at the dose of 5mg/kg with only one
      subject meeting the responder criteria at that dose. Of the remaining five
      subjects on infliximab, three crossed over to the infliximab 7.5mg/kg dose. One
      of those three subjects responded. All six patients in the placebo arm crossed
      over to the 5mg/kg dosing regimen after week 16, and two of those responded to
      infliximab. CONCLUSIONS: Infliximab therapy for patients with refractory PM and
      DM was well tolerated and may benefit a subset of patients.

PMID- 29174795
TI  - Need for positive airway pressure re-titration with changes in mask style.

PMID- 29174794
TI  - Survivin improves the early recognition of rheumatoid arthritis among patients
      with arthralgia: A population-based study within two university cities of Sweden.
AB  - OBJECTIVES: The aim of this study was to validate the use of survivin for
      preclinical recognition of rheumatoid arthritis (RA) among patients with
      unexplained arthralgia. METHODS: Serum levels of survivin and the arthritis
      specific autoantibodies RF and ACPA were measured in total of 5046 patients with
      musculoskeletal complains during 12 consecutive months in Gothenburg and in Umea.
      Among them, 303 arthralgia patients were identified and prospectively followed.
      RESULTS: After 48 months, 12.2% of the arthralgia patients developed RA. Most of
      RA cases had high serum survivin, which increased the relative risk for RA (RR =
      5.90, p = 3 * 10-7). Combination of survivin with autoantibodies was present in
      only 4.6% of the arthralgia patients and increased further the risk of RA and
      shortened time to RA development. Presence of any single autoantibody in the
      survivin-negative patients was associated with a minor risk for RA and had RA
      free survival similar to the reference group. CONCLUSION: This study shows that
      measurement of survivin in serum improves estimation of RA risk and prospectively
      predicts RA development in patients with arthralgia. Survivin may indicate a
      phase preceding autoantibody production.

PMID- 29174796
TI  - Knowledge-based treatment planning and its potential role in the transition
      between treatment planning systems.
AB  - Commissioning a new treatment planning system (TPS) involves many time-consuming
      tasks. We investigated the role that knowledge-based planning (KBP) can play in
      aiding a clinic's transition to a new TPS. Sixty clinically treated
      prostate/prostate bed intensity-modulated radiation therapy (IMRT) plans were
      exported from an in-house TPS and were used to create a KBP model in a newly
      implemented commercial application. To determine the benefit that KBP may have in
      a TPS transition, the model was tested on 2 groups of patients. Group 1 consisted
      of the first 10 prostate/prostate bed patients treated in the commercial TPS
      after the transition from the in-house TPS. Group 2 consisted of 10 patients
      planned in the commercial TPS after 8 months of clinical use. The KBP-generated
      plan was compared with the clinically used plan in terms of plan quality (ability
      to meet planning objectives and overall dose metrics) and planning efficiency
      (time required to generate clinically acceptable plans). The KBP-generated plans
      provided a significantly improved target coverage (p = 0.01) compared with the
      clinically used plans for Group 1, but yielded plans of comparable target
      coverage to the clinically used plans for Group 2. For the organs at risk, the
      KBP-generated plans produced lower doses, on average, for every normal-tissue
      objective except for the maximum dose to 0.1 cc of rectum. The time needed for
      the KBP-generated plans ranged from 6 to 15 minutes compared to 30 to 150 and 15
      to 60 minutes for manual planning in Groups 1 and 2, respectively. KBP is a
      promising tool to aid in the transition to a new TPS. Our study indicates that
      high-quality treatment plans could have been generated in the newly implemented
      TPS more efficiently compared with not using KBP. Even after 8 months of the
      clinical use, KBP still showed an increase in plan quality and planning
      efficiency compared with manual planning.

PMID- 29174797
TI  - The American Society for Apheresis (ASFA) disease registry: Past, present and
      future.

PMID- 29174798
TI  - Current status of art mobilization in Myeloma.
AB  - Multiple myeloma is the leading indication of autologous hematopoietic cell
      transplantation (AHCT) worldwide. Hematopoietic progenitor cell mobilization
      (HPCM) is the first step of a successful AHCT. A minimum of 2*106 CD34+ cells/kg
      are needed for successful engraftment. Growth factors have been used both alone
      or in combination with chemotherapy for HPCM of patients with myeloma.
      Mobilization failures result in delays in AHCT and increased cost and resource
      utility. Strategies to mobilize progenitor cells were mainly chemotherapy and
      growth factor or growth factor-only mobilization until the advent of plerixafor.
      Plerixafor is successfully integrated into both growth factor-only and
      cyclophosphamide and growth factor mobilization strategies with significantly
      reducing the mobilization failure rate in myeloma patients. The best strategy to
      mobilize progenitor cells with the highest yield and lowest toxicity and cost in
      patients with multiple myeloma has not yet been determined. This review aims to
      summarize the current status of art mobilization in myeloma comparing the pros
      and cons of different mobilization strategies.

PMID- 29174799
TI  - The emerging functions and roles of circular RNAs in cancer.
AB  - Circular RNAs (circRNAs) are a class of single-stranded closed RNA molecules that
      undergo a specific backsplicing from pre-mRNA. With the application of high
      throughput sequencing and bioinformatics, circRNAs are found to be widely
      expressed across species. Some functionally characterized circRNAs have critical
      roles in gene regulation through various actions, including sponging microRNAs
      and proteins as well as regulating transcription and splicing. Moreover, most
      circRNAs are aberrantly expressed in different cancer types, and some of them
      have been reported to play important roles in the development and progression of
      cancer. Given the lack of a 5' cap structure and evidence of their ability to
      bind with ribosomes, circRNAs were generally considered as noncoding RNA.
      Notably, recent studies reported that endogenous circRNAs can be translated with
      a cap-independent manner, which redefines the functional roles of circRNA,
      further expanding the complexity of eukaryotic transcriptomes. This review aims
      to re-evaluate the functions and roles of circRNA from the cancer perspective. It
      discusses the current understanding of circRNA functions, the emerging roles of
      circRNA in cancer, and the challenges of future studies.

PMID- 29174800
TI  - ETS1 induction by the microenvironment promotes ovarian cancer metastasis through
      focal adhesion kinase.
AB  - Metastatic colonization involves paracrine/juxtacrine interactions with the
      microenvironment inducing an adaptive response through transcriptional
      regulation. However, the identities of transcription factors (TFs) induced by the
      metastatic microenvironment in ovarian cancer (OC) and their mechanism of action
      is poorly understood. Using an organotypic 3D culture model recapitulating the
      early events of metastasis, we identified ETS1 as the most upregulated member of
      the ETS family of TFs in metastasizing OC cells as they interacted with the
      microenvironment. ETS1 was regulated by p44/42 MAP kinase signaling activated in
      the OC cells interacting with mesothelial cells at the metastatic site. Human OC
      tumors had increased expression of ETS1, which predicted poor prognosis. ETS1
      regulated OC metastasis both in vitro and in mouse xenografts. A combination of
      ChIP-seq and RNA-seq analysis and functional rescue experiments revealed FAK as
      the key transcriptional target and downstream effector of ETS1. Taken together,
      our results indicate that ETS1 is an essential transcription factor induced in OC
      cells by the microenvironment, which promotes metastatic colonization though the
      transcriptional upregulation of its target FAK.

PMID- 29174801
TI  - Dual targeting c-met and VEGFR2 in osteoblasts suppresses growth and osteolysis
      of prostate cancer bone metastasis.
AB  - Prostate cancer characteristically induces osteoblastic bone metastasis, for
      which no therapies are available. A dual kinase inhibitor of c-Met and VEGFR-2
      (cabozantinib) was shown to reduce prostate cancer growth in bone, with evidence
      for suppressing osteoblastic activity. However, c-Met and VEGFR2 signaling in
      osteoblasts in the context of bone metastasis remain unclear. Here we show using
      cultured osteoblasts that hepatocyte growth factor (HGF) and VEGF-A increased
      receptor activator of NFkappaB ligand (RANKL) and M-CSF, two essential factors
      for osteoclastogenesis. Insulin-like growth factor-1 (IGF1) also increased RANKL
      and M-CSF via c-Met transactivation. The conditioned media from IGF1-, HGF-, or
      VEGFA-treated osteoblasts promoted osteoclastogenesis that was reversed by
      inhibiting c-Met and/or VEGFR2 in osteoblasts. In vivo experiments used
      cabozantinib-resistant prostate cancer cells (PC-3 and C4-2B) to test the effects
      of c-Met/VEGFR2 inhibition specifically in osteoblasts. Cabozantinib (60 mg/kg, 3
      weeks) suppressed tumor growth in bone and reduced expression of RANKL and M-CSF
      and subsequent tumor-induced osteolysis. Collectively, inhibition of c-Met and
      VEGFR2 in osteoblasts reduced RANKL and M-CSF expression, and associated with
      reduction of tumor-induced osteolysis, suggesting that c-Met and VEGFR2 are
      promising therapeutic targets in bone metastasis.

PMID- 29174802
TI  - Targeting signaling pathways in multiple myeloma: Pathogenesis and implication
      for treatments.
AB  - Multiple myeloma (MM), which is characterized by osteolytic bone lesions, anemia,
      hypercalcemia, and renal failure, accounts for approximately 10% of all
      hematologic malignancies. Although the therapeutic landscape of MM has evolved
      spectacularly over the past decades with 5-year median survival over 50%, most of
      these patients relapse eventually. The widely recognized therapeutic approaches
      include chemotherapy, radiation, stem cell transplant, and monoclonal antibody
      therapy. Former studies have implied that the proliferation, survival, migration
      and drug resistance of MM cells are in association with the activation of several
      signaling pathways. In this review, we intended to focus on the major signaling
      pathways such as PI3K/Akt/mTOR, Ras/Raf/MEK/MAPK, JAK/STAT, NF-kappaB, Wnt/beta
      catenin, and RANK/RANKL/OPG, that contribute to the pathogenesis of the MM and
      the therapeutic approaches developed to target them.

PMID- 29174803
TI  - HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer
      via inhibiting tumor suppressor let-7g.
AB  - Methyltransferase-like 3 (METTL3) is involved in RNA metabolism through N6
      methyladenosine (m6A) modification. However, whether METTL3 participates in the
      progression of breast cancer is unclear. Aberrant expression of Mammalian
      hepatitis B X-interacting protein (HBXIP) drives the aggressiveness of breast
      cancer. Here, we are interested in the potential links between HBXIP and METTL3
      in breast cancer. We showed that the expression of METTL3 was positively related
      to that of HBXIP in clinical breast cancer tissues. Moreover, HBXIP could up
      regulate METTL3 in breast cancer cells. Mechanistically, HBXIP modulated METTL3
      by inhibiting miRNA let-7g, which down-regulated the expression of METTL3 by
      targeting its 3'UTR. Strikingly, we found that METTL3 promoted the expression of
      HBXIP through m6A modification. Furthermore, overexpressed HBXIP could rescue the
      inhibited-proliferation and enhanced-apoptosis induced by silencing of METTL3 in
      breast cancer cells. Thus, we conclude that HBXIP up-regulates METTL3 by
      suppressing let-7g, in which METTL3 increased HBXIP expression forming a positive
      feedback loop of HBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell
      proliferation in breast cancer. Our finding provides new insights into the
      mechanism of the mutual regulation between HBXIP and METTL3 in the progression of
      breast cancer.

PMID- 29174804
TI  - Organoids: An intermediate modeling platform in precision oncology.
AB  - Cancer harbors variable heterogeneity and plasticity. Thus far, our comprehension
      is greatly based on cell lines, organoids, and patient-derived tumor xenografts
      (PDTXs). Organoids are a three-dimensional in vitro culture platform constructed
      from self-organizing stem cells. They can almost accurately recapitulate tumor
      heterogeneity and microenvironment "in a dish," which surpass established cell
      lines and are not as expensive and time-consuming as PDTXs. As an intermediate
      model, tumor organoids are also used to study the fundamental issues of
      tumorigenesis and metastasis. They are specifically applied for drug testing and
      stored as "living biobanks." In this review, we highlight the translational
      applications of organoid technologies in tumor research and precision medicine,
      discuss the advantages and limitations compared with other mentioned methods, and
      provide our outlook on its future.

PMID- 29174805
TI  - Corrigendum to "Schneider membrane thickness classification evaluated by cone
      beam computed tomography and its importance in the predictability of perforation.
      Retrospective analysis of 200 patients" [Br. J. Oral Maxillofac. Surg. 54 (10)
      (December 2016) 1106-1110].

PMID- 29174806
TI  - Is routine holistic assessment with a prompt list feasible during consultations
      after treatment for oral cancer?
AB  - The head and neck cancer Patient Concerns Inventory (PCI-HN) is a holistic, self
      reported list of items that can help patients to disclose their needs and
      concerns during routine follow-up consultations. The aim of this study was to
      report how often it was used during the first three years of follow up after
      treatment for oral cancer, and the range of issues that were raised. The sample
      comprised consecutive patients treated over a three-year period with curative
      intent. All clinic attendances were reviewed until October 2015 or until patients
      had a recurrence, a subsequent primary, metastases, or were discharged home or to
      follow up at a peripheral hospital, or started palliative care. We identified 92
      patients and data were available for 88 of them. The median (IQR) age at the time
      of treatment was 65 (57-76) years, and 48 (55%) were men. Reviews alternated
      between the surgeon and oncologist, and typically there were 4.4 surgical reviews
      in year one, 2.8 in year two, and 1.6 in year three. The inventory was completed
      157 times; at least once by 71% (55/77) during year one, 57% (29/51) during year
      two, and 37% (13/35) during year three. Of those who completed none, nearly half
      (7/17) died within 12 months, and another six were over 80 years of age. In
      conclusion, the diversity of concerns raised by patients highlights the need for
      holistic assessment during follow up, and integration of the inventory into
      routine consultations will mean that we can repeat it.

PMID- 29174807
TI  - Impact of hydration and nutrition on personal performance in the clinical
      workplace.
AB  - As clinicians we sometimes fail to look after ourselves at work. We often do not
      drink enough during the day or miss lunch breaks while caring for patients, and
      this can be particularly evident during an all-day operating list when procedures
      are long and complex. Some operating theatre staff do not even eat breakfast
      regularly. Inadequate intake of fluids or nutrition can impair performance, lead
      to tiredness and headaches, and may compromise both our own health and the care
      we provide to patients. Other high-risk organisations, including aviation, have
      recognised that employees must look after themselves if they are to optimise
      their performance. In this review, we discuss the importance of adequate
      hydration and nutrition at work to raise awareness that this is essential if we
      are to provide the best care for our patients.

PMID- 29174808
TI  - Evaluation of the morphology of the genial tubercle using cone-beam computed
      tomography.

PMID- 29174809
TI  - Discovery of novel 2,4-diarylaminopyrimidine analogues as ALK and ROS1 dual
      inhibitors to overcome crizotinib-resistant mutants including G1202R.
AB  - Aiming to explore novel anaplastic lymphoma kinase (ALK) and proto-oncogene
      tyrosine-protein kinase ROS (ROS1) dual inhibitors to overcome crizotinib
      resistant mutants, two series of 2,4-diarylaminopyrimidine (DAAP) analogues
      bearing thiazole or 1,2,3-triazole moieties were designed and synthesized based
      upon the cocrystal structure of ceritinib with ALKWT (PDB 4MKC) as well as the
      binding model of ceritinib with ALKG1202R. The cellular and enzymatic assays
      validated 34c (WY-135) as a promising ALK (IC50 = 1.4 nM) and ROS1 (IC50 = 1.1
      nM) dual inhibitor superior to crizotinib and ceritinib. 34c showed significantly
      inhibitory activities on ALK-dependent cell lines KARPAS299 (IC50 = 21 nM) and
      H2228 (IC50 = 95 nM) as well as ROS1-positive cell line HCC78 (IC50 = 40 nM). In
      particular, 34c was potent against a variety of frequently observed crizotinib
      resistant mutants, particularly the L1196M mutant (IC50 = 3.1 nM) identified as
      the "gatekeeper" mutation and the G1202R mutant (IC50 = 8.7 nM) which conferred
      resistance to all clinical stage ALK inhibitors. Furthermore, 34c was capable of
      inducing cell apoptosis and strongly inhibiting cellular ALK and ROS1 activity.
      In addition, the binding models of 34c with ALKWT, ALKL1196M and ALKG1202R
      provided structural bases for SARs observations.

PMID- 29174810
TI  - Design, synthesis, and biological evaluation of new 1,2,3-triazolo-2'-deoxy-2'
      fluoro- 4'-azido nucleoside derivatives as potent anti-HBV agents.
AB  - Novel drugs are urgently needed to combat hepatitis B virus (HBV) infection due
      to drug-resistant virus. In this paper, a series of novel 4-monosubstituted 2'
      deoxy-2'-beta-fluoro-4'-azido-beta-d-arabinofuranosyl 1,2,3-triazole nucleoside
      analogues (1a-g) were designed, synthesized and screened for in vitro anti-HBV
      activity. At 5.0 MUM in the cellular model, all the synthetic compounds display
      activities comparable to that of the positive control, lamivudine at 20 MUM. Of
      the compounds tested, the amide-substituted analogue (1a) shows the most
      promising anti-HBV activity and low cytotoxicity in the cell model. In
      particular, it retains excellent activity against lamivudine-resistant HBV
      mutants. In duck HBV (DHBV)-infected duck models, both the serum and liver DHBV
      DNA levels (67.4% and 53.3%, respectively) were reduced markedly by the treatment
      with 1a. Analysis of the structure of HBV polymer/1a-triphosphate (1a-TP) complex
      shows that 1a-TP is stabilized by specific van der Waals interactions with the
      enzyme residues arising from 4-amino-1,2,3-triazole and the 4'-azido group.

PMID- 29174811
TI  - Microwave-promoted facile access to 4-aminoquinoline-phthalimides: Synthesis and
      anti-plasmodial evaluation.
AB  - Microwave promoted high yielding synthesis of 4-aminoquinoline-phthalimides was
      developed with an aim to evaluate their anti-plasmodial potential. The scaffolds
      with longer spacer length (n = 6, 8) between two pharmacophores and a halogen
      substituent on the phthalimide ring displayed good antiplasmodial activity.
      Compound 5w, with an optimum combination of hexyl chain as spacer along with a
      tetra-bromophthalimide ring proved to be most potent and non-cytotoxic among the
      series exhibiting an IC50 value of 0.10 MUM.

PMID- 29174812
TI  - Amino acid and peptide prodrugs of diphenylpropanones positive allosteric
      modulators of alpha7 nicotinic receptors with analgesic activity.
AB  - alpha7 Nicotinic acetylcholine receptors (nAChRs) are ion channels implicated in
      a number of CNS pathological processes, including pain and psychiatric, cognitive
      and inflammatory diseases. Comparing with orthosteric agonism, positive
      allosteric modulation of these channels constitutes an interesting approach to
      achieve selectivity versus other nicotinic receptors. We have recently described
      new chalcones and 1,3-diphenylpropanones as positive allosteric modulators (PAMs)
      of alpha7 nAChRs, which proved to have good analgesic activities but poor
      pharmacokinetic properties. Here we report the preparation of amino acid and
      peptide derivatives as prodrugs of these modulators with the aim of improving
      their in vivo biological activity. While the valine derivative showed very short
      half life in aqueous solutions to be considered a prodrug, Val-Val and Val-Pro
      Val are suitable precursors of the parent 1,3-diphenylpropanones, via chemical
      and enzymatic transformation, respectively. Compounds 19 (Val-Val) and 21 (Val
      Pro-Val), prodrugs of the 2',5',4-trihydroxy-1,3-diphenylpropan-1-one 3, showed
      significant antinociceptive activity in in vivo assays. The best compound, 21,
      displayed a better profile in the analgesia test than its parent compound 3,
      exhibiting about the same potency but long-lasting effects.

PMID- 29174813
TI  - Synthesis and biological evaluation of sulfur-containing shikonin oxime
      derivatives as potential antineoplastic agents.
AB  - As a continuation of our research on developing potent and potentially safe
      antineoplastic agents, a set of forty five sulfur-containing shikonin oxime
      derivatives were synthesized and evaluated for their in vitro cytotoxic activity
      against human colon cancer (HCT-15), gastric carcinoma (MGC-803), liver
      (Bel7402), breast (MCF-7) cancer cells and human skin fibroblast (HSF) cells. All
      the synthesized compounds exhibited potent cytotoxic activity selectively towards
      HCT-15 cells and did not display apparent toxicity to the normal HSF cells, some
      of which were more or comparatively effective to the parent compound against HCT
      15, MGC-803 and Bel7402 cells. The most active agent 9m displayed high potency
      against human cancer cells with IC50 ranging from 0.27 +/- 0.02 to 9.23 +/- 0.12
      MUM. The structure-activity relationships (SARs) studies suggested that the
      nature of substituent group in the side chain is important for antitumor potency
      in vitro. Additionally, nitric oxide release studies revealed that the amount of
      nitric oxide generated from these oxime derivatives was relatively low.
      Furthermore, cellular mechanism investigations indicated that compound 9m could
      arrest cell cycle at G1 phase and induce a strong apoptotic response in HCT-15
      cells. Moreover, western blot studies revealed that compound 9m induced apoptosis
      through the down-regulation of Bcl-2 and up-regulation of Bax, caspase 3 and 9.
      For all these reasons, compound 9m hold promising potential as antineoplastic
      agent.

PMID- 29174814
TI  - Design, synthesis, biological evaluation and molecular modeling of novel 2-amino
      4-(1-phenylethoxy) pyridine derivatives as potential ROS1 inhibitors.
AB  - With the aim of discovering potential and selective inhibitors targeting ROS1
      kinase, we rationally designed, synthesized and evaluated two series of novel 2
      amino-pyridine derivatives with 1-phenylethoxy at C-3 and C-4 position. The
      enzymic assays results indicated that six of the new compounds 13b-13d and 14a
      14c showed remarkably higher inhibitory activities against ROS1 kinase. The most
      promising compounds, 13d and 14c displayed the most desired ROS1 inhibitory
      activity with IC50 values of 440 nM and 370 nM respectively. Furthermore, 13d and
      14c displayed ROS1 inhibitory selectivity of about 7-fold and 12-fold, relative
      to that of ALK sharing about 49% amino acid sequence homology in the kinase
      domains. They also showed good anti-proliferative effects against ROS1-addicted
      HCC78 cell lines with the IC50 values of 8.1 MUM and 65.3 MUM, respectively.
      Moreover, molecular docking and molecular dynamics simulation studies disclosed
      that compound 14c and 13d shared similar binding poses with Crizotinib except the
      selective binding site of ROS1. It also gave a probable molecular explanation for
      their activity and selectivity, which the methoxyl group in benzene ring was the
      crucial to the selectivity to ROS1 versus ALK.

PMID- 29174815
TI  - Design, synthesis, and biological evaluation of 1,3-diarylisoquinolines as novel
      topoisomerase I catalytic inhibitors.
AB  - With a goal of identifying potent topoisomerase (topo) inhibitor, the C4-aromatic
      ring of the anticancer agent, 3,4-diarylisoquinolone, was strategically shifted
      to design 1,3-diarylisoquinoline. Twenty-two target compounds were synthesized in
      three simple and efficient steps. The 1,3-diarylisoquinolines exhibited potent
      anti-proliferative effects on cancer cells but few compounds spared non-cancerous
      cells. Inhibition of topo I/IIalpha-mediated DNA relaxation by several
      derivatives was greater than that by camptothecin (CPT)/etoposide even at low
      concentration (20 MUM). In addition, these compounds had little or no effect on
      polymerization of tubulin. A series of biological evaluations performed with the
      most potent derivative 4cc revealed that the compound is a non-intercalative topo
      I catalytic inhibitor interacting with free topo I. Collectively, the potent
      cytotoxic effect on cancer cells including the drug resistance ones, absence of
      lethal effect on normal cells, and different mechanism of action than topo I
      poisons suggest that the 1,3-diarylisoquinolines might be a promising class of
      anticancer agents worthy of further pursuit.

PMID- 29174816
TI  - Synthesis and biological evaluation of curcumin inspired imidazo[1,2-a]pyridine
      analogues as tubulin polymerization inhibitors.
AB  - With an aim to develop new curcumin inspired analogues as potent anticancer
      agents, we synthesized a series of (1E,4E)-1-phenyl-5-(3-phenylimidazo[1,2
      a]pyridin-2-yl)penta-1,4-dien-3-ones (12a-t) as tubulin polymerization
      inhibitors. An initial screening was carried out to evaluate their cytotoxic
      potential on a panel of six cancer cell lines namely, cervical (HeLa), gastric
      (HGC-27), lung (NCI-H460), prostate (DU-145 and PC-3) and breast (4T1), using MTT
      assay. Among the compounds tested, compounds 12e, 12r and 12t showed potent
      growth inhibition and 12t {(1E,4E)-1-(3-(3,4-difluorophenyl)imidazo[1,2-a]pyridin
      2-yl)-5-(2,4,6-trimethoxyphenyl)penta-1,4-dien-3-one} being the most active
      member of the series inhibited the growth of all the tested cell lines with IC50
      values varying from 1.7 - 2.97 MUM. Moreover, 12t showed promising cytotoxicity
      on PC-3, HGC-27 and HeLa cell lines with IC50 values of 2.11 +/- 0.27 MUM, 2.21
      +/- 0.25 MUM and 2.53 +/- 0.01 MUM respectively. The results from aqueous
      solubility test showed that compounds 12e and 12t have 1.7 and 2.8 times more
      aqueous solubility than curcumin. Interestingly, the most active compound 12t was
      found to be nearly 2 times more selective on PC-3 cells as well as safe on normal
      human prostate (RWPE-1) cells. In addition, compound 12t efficiently inhibited
      tubulin polymerization with IC50 value of 8.44 +/- 0.13 MUM and molecular
      modelling studies disclosed that 12t binds at the colchicine binding site of the
      tubulin. Cell cycle analysis revealed that 12t arrests PC-3 cells in G2/M phase
      in a dose dependant manner. Further, treatment of PC-3 cells with 12t showed
      typical apoptotic morphology, also led to the impairment of mitochondrial
      membrane potential (DPsim) and increased levels of reactive oxygen species (ROS).
      Altogether, the results from acridine orange/ethidium bromide (AO-EB) and DAPI
      staining studies, annexin V-FITC/propidium iodide staining assay, analysis of
      mitochondrial membrane potential (DPsim) and reactive oxygen species (ROS) levels
      undoubtedly demonstrated the induction of apoptosis in PC-3 cells by compound
      12t.

PMID- 29174817
TI  - [Bladder cancer in neurogenic patients: A retrospective study of management and
      follow-up].
AB  - INTRODUCTION: The prevalence of bladder cancer (BC) in neurological patients
      seems to be similar to that of the general population. However, they are more
      aggressive with a higher rate of muscle-invasive forms and squamous cells
      carcinomas. The aim of the current study was to report etiologies, management and
      outcomes of BC in neurological population. MATERIAL AND METHOD: Were enrolled all
      neurological patients with a BC diagnosed between 2004 and 2017. The following
      data were retrospectively reported: age, gender, duration of the disease, mode of
      discovery, histological type, treatment and outcomes. RESULTS: In total, 27
      patients were included: 11 spinal cord injuries, 7 Parkinson's disease, 5
      multiple sclerosis, 3 head trauma, 3 brain strokes, 2 cerebral palsies and 1
      spina bifida. The histological subtypes were as follows: 22 transitional cells
      carcinomas, 4 squamous cell carcinomas (SCC), one mucinous adenocarcinoma, one
      sarcomatoid and one neuroendocrine with 19 high-grade tumors and 15 muscle
      invasive bladder cancer. Seven patients (26%) were diagnosed before 15 years
      history of neurogenic bladder. The mean follow-up was 14 months (1-210 months).
      Eight deaths were observed, with 5 related to bladder cancer. In our study,
      smoking habits, voiding mode, lithiasis or infection histories were not related
      with a more aggressive pattern, such as SCC. CONCLUSION: The high rate of muscle
      invasive bladder cancer and aggressive patterns justify neuro-urological follow
      up, even before 15 years of neurogenic bladder. LEVEL OF EVIDENCE: 4.

PMID- 29174818
TI  - Inhibition of advanced glycation endproduct (AGE) rescues against streptozotocin
      induced diabetic cardiomyopathy: Role of autophagy and ER stress.
AB  - Diabetes mellitus leads to oxidative stress and contractile dysfunction in the
      heart. Although several rationales have been speculated, the precise mechanism
      behind diabetic cardiomyopathy remains elusive. This study was designed to assess
      the role of inhibition of advanced glycation endproducts (AGE) in streptozotocin
      (STZ)-induced diabetic cardiac dysfunction. Cardiac contractile function was
      assessed in normal C57BL/6 and STZ (200mg/kg, single injection and maintained for
      2 wks)-induced diabetic mice treated with or without the AGE inhibitor
      aminoguanidine (50mg/kg/d in drinking water) for 2 weeks using echocardiography
      and IonOptix MyoCam techniques. Diabetes compromised cardiac contractile function
      shown as reduced fractional shortening and ejection fraction, enlarged left
      ventricular end systolic/diastolic diameters, decreased peak shortening, maximal
      velocity of shortening/relengthening, prolonged shortening and relengthening
      duration as well as impaired intracellular Ca2+ homeostasis, the effects of which
      were alleviated or reversed by aminoguanidine treatment. Diabetes also inhibited
      autophagy, increased ER stress and phosphorylation of pro-hypertrophic signaling
      molecules Akt and mTOR, the effect of which was reversed by aminoguanidine. In
      vitro study revealed that methylglyoxal-derived AGE (MG-AGE) incubation in
      isolated cardiomyocytes promoted oxidation of sarco(endo)plasmic reticulum Ca2+
      ATPase (SERCA2a) and production of superoxide, the effects of which were negated
      by the autophagy inducer rapamycin, the ER stress chaperone TUDCA or the
      antioxidant N-acetylcysteine. Taken together, these data revealed that inhibition
      of AGE formation rescues against experimental diabetes-induced cardiac remodeling
      and contractile dysfunction possible through regulation of autophagy and ER
      stress.

PMID- 29174820
TI  - Effect of rat parental morphine exposure on passive avoidance memory and morphine
      conditioned place preference in male offspring.
AB  - Drug addiction is a chronic disorder resulted from complex interaction of
      genetic, environmental, and developmental factors. Epigenetic mechanisms play an
      important role in the development and maintenance of addiction and also memory
      formation in the brain. We have examined passive avoidance memory and morphine
      conditioned place preference (CPP) in the offspring of male and/or female rats
      with a history of adulthood morphine consumption. Adult male and female animals
      received chronic oral morphine for 21days and then were maintained drug free for
      10days. After that, they were let to mate with either an abstinent or control
      rat. Male offspring's memory was evaluated by step through test. Besides,
      rewarding effects of morphine were checked with CCP paradigm. Offspring of
      abstinent animals showed significant memory impairment compared to the control
      group which was more prominent in the offspring of abstinent females.
      Conditioning results showed that administration of a high dose of morphine
      (10mg/kg) that could significantly induce CPP in control rats, was not able to
      induce similar results in the offspring of morphine abstinent parents; and CPP
      was much more prominent when it was induced in the offspring of morphine exposed
      females compared to the progeny of morphine exposed males. It is concluded that
      parental morphine consumption in adulthood even before mating has destructive
      effects on memory state of the male offspring and also leads to tolerance to the
      rewarding effects of morphine. These effects are greater when the morphine
      consumer parent is the female one.

PMID- 29174821
TI  - The impact of care management information technology model on quality of care
      after percutaneous coronary intervention: "Bridging the Divides".
AB  - BACKGROUND: Reducing readmissions and improving metrics of care are a national
      priority. Supplementing traditional care with care management may improve
      outcomes. The Bridges program was an initial evaluation of a care management
      platform (CareLinkHub), supported by information technology (IT) developed to
      improve the quality and transition of care from hospital to home after
      percutaneous coronary intervention (PCI) and reduce readmissions. METHODS:
      CareLink is comprised of care managers, patient navigators, pharmacists and
      physicians. Information to guide care management is guided by a middleware layer
      to gather information, PLR (ColdLight Solutions, LLC) and presented to CareLink
      staff on a care management platform, AerialTM (Medecision). An additional
      analytic engine [NeuronTM (ColdLight Solutions, LLC)] helps, evaluates and guide
      care. RESULTS: The "Bridges" program enrolled a total of 2054 PCI patients with
      2835 admission from April, 1st 2013 through March 1st, 2015. The data of the
      program was compared with those of 3691 PCI patients with 4414 admissions in the
      3years prior to the program. No impact was seen with respect to inpatient and
      observation readmission, or emergency department visits. Similarly no change was
      noticed in LDL control. There was minimal improvement in BP control and only in
      the CTM-3 and SAQ-7 physical limitation scores in the patients' reported
      outcomes. Patient follow-up with physicians within 1week of discharge improved
      during the Bridges years. CONCLUSIONS: The CareLink hub platform was successfully
      implemented. Little or no impact on outcome metrics was seen in the short follow
      up time. The Bridges program suggests that population health management must be a
      long-term goal, improving preventive care in the community.

PMID- 29174822
TI  - Acute procedural outcomes of orbital atherectomy for the treatment of iliac
      artery disease: Sub-analysis of the CONFIRM registries.
AB  - Endovascular intervention is an appealing revascularization strategy for iliac
      artery disease. Atherectomy of the iliac artery is uncommon due to the risk of
      life-threatening perforation but may be necessary if the iliac lesion is heavily
      calcified, preventing stent delivery or optimal expansion. We assessed the
      feasibility and safety of orbital atherectomy for the treatment of iliac artery
      disease. Demographic data, lesion characteristics, and procedure outcomes for the
      CONFIRM patients with at least one iliac artery lesion treated with orbital
      atherectomy (n=62 patients; n=68 lesions) were compared to patients with at least
      one superficial femoral artery (SFA) lesion treated with orbital atherectomy
      (n=1570 patients; n=1809 lesions). The procedural complication rate, defined as
      the composite of flow limiting dissection, perforation, slow flow, vessel
      closure, spasm, embolism, or thrombosis, was compared in iliac lesions versus SFA
      lesions. The iliac artery group had more patients with diabetes, shorter lesions,
      and more severely calcified lesions. The orbital atherectomy run time was
      significantly shorter in the iliac artery group. Additionally, in the iliac group
      there was one reported perforation and one reported vessel closure; the rates of
      slow flow, spasm, embolism, thrombus, and flow limiting dissection were 0%. The
      overall procedural complication rate was significantly lower in the iliac group
      (2.9% vs. 11.2%, p=0.03). Orbital atherectomy of the iliac artery is feasible
      with few reported angiographic complications and compared favorably with the SFA
      group. Orbital atherectomy may be considered to facilitate the delivery and
      expansion of a balloon or stent if the iliac artery is calcified.

PMID- 29174819
TI  - Considering sex differences in the cognitive controls of feeding.
AB  - Women are disproportionately affected by obesity, and obesity increases women's
      risk of developing dementia more so than men. Remarkably little is known about
      how females make decisions about when and how much to eat. Research in animal
      models with males supports a framework in which previous experiences with
      external food cues and internal physiological energy states, and the ability to
      retrieve memories of the consequences of eating, determines subsequent food
      intake. Additional evidence indicates that consumption of a high-fat, high-sugar
      diet interferes with hippocampal-dependent mnemonic processes that operate to
      suppress eating, such as in situations of satiety. Recent findings also indicate
      that weakening this form of hippocampal-dependent inhibitory control may also
      extend to other forms of learning and memory, perpetuating a vicious cycle of
      increased Western diet intake, hippocampal dysfunction, and further impairments
      in the suppression of appetitive behavior that may ultimately disrupt other types
      of memorial interference resolution. How these basic learning and memory
      processes operate in females to guide food intake has received little attention.
      Ovarian hormones appear to protect females from obesity and metabolic
      impairments, as well as modulate learning and memory processes, but little is
      known about how these hormones modulate learned appetitive behavior. Even less is
      known about how a sex-specific environmental factor - widespread hormonal
      contraceptive use - affects associative learning and the regulation of food
      intake. Extending learned models of food intake to females will require
      considerably investigation at many levels (e.g., reproductive status, hormonal
      compound, parity). This work could yield critical insights into the etiology of
      obesity, and its concomitant cognitive impairment, for both sexes.

PMID- 29174823
TI  - Modified balloon aortic valvuloplasty in fragile symptomatic patients unsuitable
      for both surgical and percutaneous valve replacement.
AB  - BACKGROUND: Balloon Aortic valvuloplasty (BAV) is considered as a bridge therapy
      to percutaneous valve implantation or a palliative treatment in patients with
      aortic valve stenosis (AVS). Potential risk of complications, in particular in
      fragile patients, is still not negligible. AIM: To describe the technique and
      outcomes of modified BAV in fragile symptomatic patients unsuitable for other
      treatments using no-pacing and minimally invasive approach. METHODS: Symptomatic
      fragile patients with severe aortic valve stenosis judged unsuitable by the heart
      team for surgical or percutaneous valve implantation from 1 September 2013 to 1
      September 2017 were offered modified BAV. Simplified procedural protocol included
      a 4F right radial artery access for gradient check, a 8F compatible undersized
      balloons, two partial inflations-trial before a full inflation with no-pace maker
      back-up, final pressure gradient recording and aortography. RESULTS: Thirty-four
      symptomatic fragile patients (mean age 80.9+/-4.9, range 73 to 91years, 100% Katz
      >6, mean Euroscore I 30.0+/-11.7%) underwent modified BAV in the last 5years with
      immediate success in all (100%). Mean aortic valve area increased from 0.58+/
      0.2cm2 to 1.1+/-0.2cm2 (p<0.01) whereas mean peak gradient decreased from 75.6+/
      11.3 to 35.8+/-11.2mmHg (p<0.01). Procedural complications were 14.7%. Thirty-day
      mortality was 11.8%. On a mean follow up of 38.4+/-4.6months four patients
      successfully repeated the procedure, while global mortality was 23.5% (8
      patients). The other 22 patients maintained a NYHA class of 2.1+/-0.7.
      CONCLUSIONS: No-pacing minimally invasive BAV seems to have acceptable outcomes
      in patients with severe AVS and no other treatment options.

PMID- 29174824
TI  - Intraprocedural invasive hemodynamic parameters as predictors of short- and long
      term outcomes in patients undergoing transcatheter aortic valve replacement.
AB  - OBJECTIVE: Evaluation of invasive hemodynamic parameters as prognostic markers of
      mortality in patients undergoing TAVR. BACKGROUND: The value of invasive
      intraprocedural hemodynamic evaluation of patients undergoing transcatheter
      aortic valve replacement is unclear. METHODS: Consecutive patients who underwent
      transfemoral TAVR and had complete prospectively collected intraprocedural
      invasive hemodynamic parameters were retrospectively analyzed. Patients with
      alternative access, planned general anesthesia, or baseline >=moderate Tricuspid
      Regurgitation were excluded. Pre- and post-valve implant parameters included
      heart rate, systolic and diastolic blood pressures, cardiac output and index,
      pulmonary arterial systolic and diastolic pressures, transaortic pressure
      gradient and right atrial pressure. The primary end points were the association
      of the intraprocedural hemodynamic changes with all-cause mortality at 30days and
      1year. Extensive Receiver Operating Characteristic analyses yielded dichotomized
      threshold of hemodynamic values in association with the binary outcome of
      mortality. RESULTS: A total of 312 patients (52% male, mean age 83years) were
      evaluated. A significant association with 30-day and 1-year mortality was found
      between intraprocedural post-valve implant cardiac index <1.9 vs. >=1.9L/min/m2
      (Log-ranked p=0.0286 and p=0.0432, respectively). Four subgroups with pre- and
      post-valve implant CI changes (L/min/m2) were compared: [1] pre<1.9,
      stable_post<1.9; [2] pre<1.9, improved_post>=1.9; [3] pre>=1.9, stable_post>=1.9;
      and [4] pre>=1.9, worsened_post<1.9. Group 1 (lower CI with no post-valve
      improvement) had the worst survival, and Group 3 (higher CI and stable post
      valve) had the best survival at 1-year follow-up (Log-ranked p=0.0089).
      CONCLUSIONS: In patients with severe aortic stenosis undergoing TAVR, invasive
      monitoring can assess for hemodynamic prognostic markers of survival.

PMID- 29174825
TI  - When intravascular ultrasound becomes indispensable in percutaneous coronary
      intervention of a chronic total occlusion.
AB  - Percutaneous coronary intervention of chronic total occlusion is a particular
      interventional area which requires high level of operator's experience and the
      support of additional tools based on intracoronary image such as intravascular
      ultrasound in many cases to clarify difficulties during procedures and to
      increase success rate. Implantation of long stents in many cases, the presence of
      stump ambiguity, and the use of specific techniques in this kind of
      interventions, such as reverse controlled antegrade and retrograde subintimal
      tracking (CART) and reverse CART make necessary in many cases the use of
      intravascular ultrasound for a better understanding of the situation, for
      reducing eventual complications and increasing procedural success rate. We made a
      review of literature related to most challenging situations in which the use of
      intravascular ultrasound during chronic total occlusion percutaneous coronary
      intervention becomes rather indispensable to safely continue and finish the
      procedure. Besides, two complex percutaneous coronary interventions of chronic
      total occlusion with unfavourable anatomic features in which intravascular
      ultrasound was crucial for the procedural success are presented in this
      manuscript along with support of the literature.

PMID- 29174826
TI  - Predicting of ultrafiltration performances by advanced data analysis.
AB  - In order to optimize drinking water production operation, membrane users can use
      several analytical tools that help membrane fouling prediction and alleviate
      fouling by a proper feed water resource selection. However, during strong fouling
      event, membrane decision-makers still face short-term deadline to decide between
      different options (e.g. optimization of pretreatment or change in feed water
      quality). Hence, statistical approach might help to better select the most
      relevant analytical parameter related to fouling potential of a specific resource
      in order to speed-up decision taking. In this study, the physical and chemical
      properties and the filtration performances (at lab-scale) of five ground water
      resources, selected as potential resources of a large drinking production site of
      Paris (France), was evaluated through one year. Principal component analysis
      emphasizes the strong link between waters' organic matrix and fouling propensity.
      Cluster analysis of filtration performances allowed classifying the water samples
      into three groups exhibiting strong, low and intermediate fouling. Finally,
      multiple linear regressions performed on all collected data indicated that strong
      fouling events were related to a combined increase of carbon content and protein
      like-substances while intermediate fouling might only be anticipated by an
      increase of fluorescence signal associated to protein like-substances. This study
      demonstrates that advanced data analysis might be a powerful tool to better
      manage water resources selection used for drinking water production and to
      forecast filtration performances in a context of water quality degradation.

PMID- 29174827
TI  - Transport of iron nanoparticles through natural discrete fractures.
AB  - The transport of nano scale iron particles (NIP) in fractures is of concern for
      remediation of both fractured aquifers and porous aquifers when hydro-fracking
      and flow in preferential pathways takes place. In this study the transport of
      various NIP in a natural discrete fractured chalk core was investigated and their
      mass recoveries calculated. Four different types of NIP were tested and
      characterized in two ionic strength (IS) solutions at a particle concentration of
      100-200 mg/l. The effect of IS, stability (sedimentation rate), particle size,
      solution viscosity and stabilizer were studied. NIP stability ranged from 1 to
      100% following 120 min of stability tests and recoveries ranged from about 6 to
      69%. The stabilizer type and concentration were shown to have significant role in
      NIP recoveries, especially at increased IS. It was evident that gravitational
      stability is the most crucial factor dominating transport of NIP. Accordingly,
      stability tests were shown to be a reliable indicator of NIP mobility. The high
      recoveries of some NIP tested, combined with the lack of clogging effect
      illustrates the enhanced mobility of NIP in fractures. The wide range of
      recoveries indicates NIP transport manipulation potential in such media. We
      therefore suggest that application of NIP in contaminated fractures has
      considerable potential as a remediation measure. In order to achieve NIP
      distribution in the aquifer while avoiding leakage to the environment, NIP
      stabilizer concentration should be adjusted according to the site-specific
      hydrogeochemical properties of the contaminated media.

PMID- 29174828
TI  - Wet biowaste digestion: ADM1 model improvement by implementation of known genera
      and activity of propionate oxidizing bacteria.
AB  - Anaerobic digestion of biowaste not only reduces environmental burden but also
      plays an important role for sustainable energy supply. For process optimization
      simulation based on the Anaerobic Digestion Model No. 1 (ADM1) is commonly used.
      The ADM1 was extended to include the known three genera of propionate oxidizing
      bacteria (POB) and the two routes of propionate degradation (methyl-malonyl CoA
      and C6-dismutation pathway). Kinetic parameters for anaerobic propionate
      oxidation by single strains of the three propionate oxidizing genera were
      determined from defined tri-cultures of the POB with hydrogenotrophic and
      acetotrophic methanogens and implemented into ADM1. The such improved model
      ADM1xpro was evaluated with operational data from a full scale wet biowaste
      digestion plant. Predicted amounts of biogas and composition with ADM1xpro (2201
      m3 d-1, 68.1 % CH4 and 31.9 % CO2) correlated well with full-scale process data
      (2171 m3 d-1, 67.5 % CH4 and 31.9 % CO2).

PMID- 29174829
TI  - Intrinsic tradeoff between kinetic and energetic efficiencies in membrane
      capacitive deionization.
AB  - Significant progress has been made over recent years in capacitive deionization
      (CDI) to develop novel system configurations, predictive theoretical models, and
      high-performance electrode materials. To bring CDI to large scale practical
      applications, it is important to quantitatively understand the intrinsic tradeoff
      between kinetic and energetic efficiencies, or the relationship between energy
      consumption and the mass transfer rate. In this study, we employed both
      experimental and modeling approaches to systematically investigate the tradeoff
      between kinetic and energetic efficiencies in membrane CDI (MCDI). Specifically,
      we assessed the relationship between the average salt adsorption rate and
      specific energy consumptions from MCDI experiments with different applied current
      densities but a constant effluent salinity. We investigated the impacts of feed
      salinity, diluted water salinity, diluted water volume per charging cycle, and
      electrode materials on the kinetics-energetics tradeoff. We also demonstrate how
      this tradeoff can be employed to optimize the design and operation of CDI systems
      and compare the performance of different electrode materials and CDI systems.

PMID- 29174830
TI  - Influence of Shift Duration on Cognitive Performance of Emergency Physicians: A
      Prospective Cross-Sectional Study.
AB  - STUDY OBJECTIVE: The relationship between tiredness and medical errors is now
      commonly accepted. The main objective of this study is to evaluate the cognitive
      performance of emergency physicians after a night shift of 14 hours (H14) and
      after a work shift of 24 hours (H24) and to compare it with tests performed after
      a rest night at home (H0). METHODS: Forty emergency physicians (19 staff
      physicians and 21 residents) were randomly evaluated at H0, H14, and H24. Four
      cognitive abilities (processing speed, working memory capacity, perceptual
      reasoning, and cognitive flexibility) were tested according to the Wechsler Adult
      Intelligence Scale and the Wisconsin Card Sorting Test. RESULTS: No cognitive
      ability was significantly altered after H14 compared with H0. Three of 4
      cognitive abilities were impaired at H24 compared with H0: processing speed (11.2
      [SD 2.7] versus 12.4 [SD 3.2]; mean difference=-1.2 [95% confidence interval -1.9
      to -0.5]), working memory capacity (10.1 [SD 2.9] versus 11.6 [SD 3.0]; mean
      difference=-1.5 [95% confidence interval -2.2 to -0.8]), and perceptual reasoning
      (8.4 [SD 2.7] versus 10.6 [SD 2.8]; mean difference=-2.2 [95% confidence interval
      -3.4 to -1.0]). Cognitive abilities were not different between residents and
      staff physicians (except for perceptual reasoning) and were not affected by the
      amount of sleep during the night shift. CONCLUSION: The cognitive abilities of
      emergency physicians were significantly altered after a 24-hour shift, whereas
      they were not significantly different from the rested condition after a 14-hour
      night shift. Limiting 24-hour shift work for emergency physicians should be
      considered and further evaluated.

PMID- 29174831
TI  - Is the Risk of Bleeding Among Older Adults With Atrial Fibrillation Lower With
      Antiplatelet Compared With Oral Anticoagulants?

PMID- 29174832
TI  - The Successes and Challenges of Integrating Emergency Medicine With Critical Care
      Medicine.

PMID- 29174833
TI  - Does Prescription Opioid Shopping Increase Overdose Rates in Medicaid
      Beneficiaries?
AB  - STUDY OBJECTIVE: The link between prescription opioid shopping and overdose
      events is poorly understood. We test the hypothesis that a history of
      prescription opioid shopping is associated with increased risk of overdose
      events. METHODS: This is a secondary analysis of a linked claims and controlled
      substance dispense database. We studied adult Medicaid beneficiaries in 2014 with
      prescription opioid use in the 6 months before an ambulatory care or emergency
      department visit with a pain-related diagnosis. The primary outcome was a
      nonfatal overdose event within 6 months of the cohort entry date. The exposure of
      interest (opioid shopping) was defined as having opioid prescriptions by
      different prescribers with greater than or equal to 1-day overlap and filled at 3
      or more pharmacies in the 6 months before cohort entry. We used a propensity
      score to match shoppers with nonshoppers in a 1:1 ratio. We calculated the
      absolute difference in outcome rates between shoppers and nonshoppers. RESULTS:
      We studied 66,328 patients, including 2,571 opioid shoppers (3.9%). There were
      290 patients (0.4%) in the overall cohort who experienced a nonfatal overdose. In
      unadjusted analyses, shoppers had higher event rates than nonshoppers (rate
      difference of 4.4 events per 1,000; 95% confidence interval 0.8 to 7.9). After
      propensity score matching, there were no outcome differences between shoppers and
      nonshoppers (rate difference of 0.4 events per 1,000; 95% confidence interval 
      4.7 to 5.5). These findings were robust to various definitions of opioid shoppers
      and look-back periods. CONCLUSION: Prescription opioid shopping is not
      independently associated with increased risk of overdose events.

PMID- 29174834
TI  - A Systematic Review and Meta-Analysis of the Management and Outcomes of Isolated
      Skull Fractures in Children.
AB  - STUDY OBJECTIVE: Most studies of children with isolated skull fractures have been
      relatively small, and rare adverse outcomes may have been missed. Our aim is to
      quantify the frequency of short-term adverse outcomes of children with isolated
      skull fractures. METHODS: PubMed, EMBASE, the Cochrane Library, Scopus, Web of
      Science, and gray literature were systematically searched to identify studies
      reporting on short-term adverse outcomes of children aged 18 years or younger
      with linear, nondisplaced, isolated skull fractures (ie, without traumatic
      intracranial injury on neuroimaging). Two investigators independently reviewed
      identified articles for inclusion, assessed quality, and extracted relevant data.
      Our primary outcome was emergency neurosurgery or death. Secondary outcomes were
      hospitalization and new intracranial hemorrhage on repeated neuroimaging. Meta
      analyses of pooled estimate of each outcome were conducted with random-effects
      models, and heterogeneity across studies was assessed. RESULTS: Of the 587
      studies screened, the 21 that met our inclusion criteria included 6,646 children
      with isolated skull fractures. One child needed emergency neurosurgery and no
      children died (pooled estimate 0.0%; 95% confidence interval [CI] 0.0% to 0.0%;
      I2=0%). Of the 6,280 children with known emergency department disposition, 4,914
      (83%; 95% CI 71% to 92%; I2=99%) were hospitalized. Of the 569 children who
      underwent repeated neuroimaging, 6 had new evidence of intracranial hemorrhage
      (0.0%; 95% CI 0.0% to 9.0%; I2=77%); none required operative intervention.
      CONCLUSION: Children with isolated skull fractures were at extremely low risk for
      emergency neurosurgery or death, but were frequently hospitalized. Clinically
      stable children with an isolated skull fracture may be considered for outpatient
      management in the absence of other clinical concerns.

PMID- 29174835
TI  - Diagnosing Patients With Acute-Onset Persistent Dizziness.

PMID- 29174836
TI  - Accuracy and Reliability of Emergency Department Triage Using the Emergency
      Severity Index: An International Multicenter Assessment.
AB  - STUDY OBJECTIVE: We assess accuracy and variability of triage score assignment by
      emergency department (ED) nurses using the Emergency Severity Index (ESI) in 3
      countries. In accordance with previous reports and clinical observation, we
      hypothesize low accuracy and high variability across all sites. METHODS: This
      cross-sectional multicenter study enrolled 87 ESI-trained nurses from EDs in
      Brazil, the United Arab Emirates, and the United States. Standardized triage
      scenarios published by the Agency for Healthcare Research and Quality (AHRQ) were
      used. Accuracy was defined by concordance with the AHRQ key and calculated as
      percentages. Accuracy comparisons were made with one-way ANOVA and paired t test.
      Interrater reliability was measured with Krippendorff's alpha. Subanalyses based
      on nursing experience and triage scenario type were also performed. RESULTS: Mean
      accuracy pooled across all sites and scenarios was 59.2% (95% confidence interval
      [CI] 56.4% to 62.0%) and interrater reliability was modest (alpha=.730; 95% CI
      .692 to .767). There was no difference in overall accuracy between sites or
      according to nurse experience. Medium-acuity scenarios were scored with greater
      accuracy (76.4%; 95% CI 72.6% to 80.3%) than high- or low-acuity cases (44.1%,
      95% CI 39.3% to 49.0% and 54%, 95% CI 49.9% to 58.2%), and adult scenarios were
      scored with greater accuracy than pediatric ones (66.2%, 95% CI 62.9% to 69.7%
      versus 46.9%, 95% CI 43.4% to 50.3%). CONCLUSION: In this multinational study,
      concordance of nurse-assigned ESI score with reference standard was universally
      poor and variability was high. Although the ESI is the most popular ED triage
      tool in the United States and is increasingly used worldwide, our findings point
      to a need for more reliable ED triage tools.

PMID- 29174838
TI  - Lactate Levels in Patients Receiving Hemodialysis: A Confounder in the Assessment
      of Infected Patients.

PMID- 29174837
TI  - Accuracy and Discomfort of Different Types of Intranasal Specimen Collection
      Methods for Molecular Influenza Testing in Emergency Department Patients.
AB  - STUDY OBJECTIVE: While development is under way of accurate, point-of-care
      molecular tests for influenza infection, the optimal specimen type for molecular
      tests remains unclear. Compared with standard nasopharyngeal swab specimens, less
      invasive nasal swab and midturbinate swab specimens may cause less patient
      discomfort and be more suitable for routine emergency department (ED) testing,
      although possibly at the expense of diagnostic accuracy. We compare both the
      accuracy of a polymerase chain reaction molecular influenza test and discomfort
      between these 3 intranasal specimen types. METHODS: A convenience sample of adult
      and pediatric patients with influenza-like illness and presenting to 2 Northern
      California EDs and 2 EDs in Santiago, Chile, was prospectively enrolled during
      the 2015 to 2016 influenza season. Research nurses collected nasopharyngeal swab,
      midturbinate swab, and nasal swab specimens from each subject and assessed
      discomfort on a validated 6-point scale. Specimens were tested for influenza A
      and B by real-time polymerase chain reaction at reference laboratories. Outcome
      measures were comparison of test performance between nasal swab and midturbinate
      swab, when compared with a reference standard nasopharyngeal swab; and comparison
      of discomfort between all 3 specimen types. RESULTS: Four hundred eighty-four
      subjects were enrolled, and all 3 swabs were obtained for each subject; 14% were
      children. The prevalence of influenza (A or B) was 30.0% (95% confidence interval
      [CI] 26.0% to 34.8%). The sensitivity for detecting influenza was 98% (95% CI
      94.25% to 99.65%) with the midturbinate swab versus 84.4% (95% CI 77.5% to 89.8%)
      with the nasal swab, difference 13.6% (95% CI 8.2% to 19.3%). Specificity was
      98.5% (95% CI 96.6% to 99.5%) with the midturbinate swab versus 99.1% (95% CI
      97.4% to 99.8%) with the nasal swab, difference -0.6% (95% CI -1.8% to 0.6%).
      Swab discomfort levels correlated with the depth of the swab type. Median
      discomfort scores for the nasal swab, midturbinate swab, and nasopharyngeal swab
      were 0, 1, and 3, respectively; the median differences were nasopharyngeal swab
      midturbinate swab 2 (95% CI 1 to 2), nasopharyngeal swab-nasal swab 3 (95% CI 2
      to 3), and midturbinate swab-nasal swab 1 (95% CI 1 to 2). CONCLUSION: Compared
      with the reference standard nasopharyngeal swab specimen, midturbinate swab
      specimens provided a significantly more comfortable sampling experience, with
      only a small sacrifice in sensitivity for influenza detection. Nasal swab
      specimens were significantly less sensitive than midturbinate swab. Our results
      suggest the midturbinate swab is the sampling method of choice for molecular
      influenza testing in ED patients.

PMID- 29174839
TI  - A National Study of Outpatient Health Care Providers' Effect on Emergency
      Department Visit Acuity and Likelihood of Hospitalization.
AB  - STUDY OBJECTIVE: Many policymakers believe that expanding access to outpatient
      care will reduce emergency department (ED) use. However, outpatient health care
      providers often refer their patients to EDs for evaluation and management. We
      examine the factors underlying outpatient provider referral, its effect on ED
      visit volume, and whether referred ED visits are more likely to result in
      hospitalization than self-referred visits. METHODS: We conducted a cross
      sectional study of 19,342 adult (>18 years) respondents to the 2012 to 2014
      National Health Interview Survey who reported they had visited an ED at least
      once in the past 12 months, representing an estimated 44,152,870 US adults. We
      categorized individuals as having been referred to the ED by an outside health
      care provider if they responded affirmatively to "your health care provider
      advised you to go" as a reason for their most recent ED visit. We performed
      descriptive analyses and logistic regressions to examine factors associated with
      outpatient health care provider referral to the ED. Respondents could choose
      multiple other reasons for their most recent ED visit, and we used existing
      Centers for Disease Control and Prevention guidelines to group these reasons into
      2 categories: seriousness of the medical condition and lack of access to other
      providers. Our 2 main outcomes were whether an outpatient health care provider
      referred an individual to the ED and whether that ED visit resulted in
      hospitalization. RESULTS: Of the 44,152,870 US adults (18.58%; 95% confidence
      interval [CI] 18.21% to 18.95%) with one or more ED visits in the previous 12
      months, 10,913,271 (24.72%; 95% CI 23.80% to 25.64%) were referred to the ED by
      an outpatient provider. Respondents who reported their ED visit was due to the
      seriousness of their medical condition were more likely to be referred to the ED
      (odds ratio [OR] 2.18; 95% CI 1.91 to 2.49), whereas those reporting a lack of
      access to other providers were less likely to be referred (OR 0.58; 95% CI 0.52
      to 0.64). Visits referred to the ED were more likely to result in hospitalization
      than self-referrals (OR 2.07; 95% CI 1.87 to 2.31). CONCLUSION: Almost one
      quarter of individuals' most recent ED visits were driven by referrals from
      outpatient health care providers. Being referred to the ED by an outpatient
      provider is strongly associated with the seriousness of one's medical condition,
      which also increases the odds of hospitalization compared with ED discharge.
      After controlling for seriousness of medical condition, ED referral by an
      outpatient provider continues to have an independent association with
      hospitalization.

PMID- 29174840
TI  - Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential
      nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis
      therapy via in-silico-in-vitro-in-vivo approach.
AB  - Recent tuberculosis (TB) drug discovery programme involve continuous pursuit for
      new chemical entity (NCE) which can be not only effective against both
      susceptible and resistant strains of Mycobacterium tuberculosis (Mtb) but also
      safe and faster acting with the target, thereby shortening the prolonged TB
      treatments. We have identified a potential nitrofuranyl methyl piperazine
      derivative, IIIM-MCD-211 as new antitubercular agent with minimum inhibitory
      concentration (MIC) value of 0.0072 MUM against H37Rv strain. Objective of the
      present study is to investigate physicochemical, pharmacokinetic, efficacy and
      toxicity profile using in-silico, in-vitro and in-vivo model in comprehensive
      manner to assess the likelihood of developing IIIM-MCD-211 as a clinical
      candidate. Results of computational prediction reveal that compound does not
      violate Lipinski's, Veber's and Jorgensen's rule linked with drug like properties
      and oral bioavailability. Experimentally, IIIM-MCD-211 exhibits excellent
      lipophilicity that is optimal for oral administration. IIIM-MCD-211 displays
      evidence of P-glycoprotein (P-gp) induction but no inhibition ability in
      rhodamine cell exclusion assay. IIIM-MCD-211 shows high permeability and plasma
      protein binding based on parallel artificial membrane permeability assay (PAMPA)
      and rapid equilibrium dialysis (RED) assay model, respectively. IIIM-MCD-211 has
      adequate metabolic stability in rat liver microsomes (RLM) and favourable
      pharmacokinetics with admirable correlation during dose escalation study in Swiss
      mice. IIIM-MCD-211 has capability to appear into highly perfusable tissues. IIIM
      MCD-211 is able to actively prevent progression of TB infection in chronic
      infection mice model. IIIM-MCD-211 shows no substantial cytotoxicity in HepG2
      cell line. In acute toxicity study, significant increase of total white blood
      cell (WBC) count in treatment group as compared to control group is observed.
      Overall, amenable preclinical data make IIIM-MCD-211 ideal candidate for further
      development of oral anti-TB agent.

PMID- 29174841
TI  - New hope for hyperlipidemia management: Inclisiran.

PMID- 29174842
TI  - Oligonucleotide Therapies for the Lung: Ready to Return to the Clinic?

PMID- 29174843
TI  - An Efficient Single-Cell RNA-Seq Approach to Identify Neoantigen-Specific T Cell
      Receptors.
AB  - The adoptive transfer of neoantigen-reactive tumor-infiltrating lymphocytes
      (TILs) can result in tumor regression in patients with metastatic cancer. To
      improve the efficacy of adoptive T cell therapy targeting these tumor-specific
      mutations, we have proposed a new therapeutic strategy, which involves the
      genetic modification of autologous T cells with neoantigen-specific T cell
      receptors (TCRs) and the transfer of these modified T cells back to cancer
      patients. However, the current techniques to isolate neoantigen-specific TCRs are
      labor intensive, time consuming, and technically challenging, not suitable for
      clinical applications. To facilitate this process, a new approach was developed,
      which included the co-culture of TILs with tandem minigene (TMG)-transfected or
      peptide-pulsed autologous antigen-presenting cells (APCs) and the single-cell RNA
      sequencing (RNA-seq) analysis of T cells to identify paired TCR sequences
      associated with cells expressing high levels of interferon-gamma (IFN-gamma) and
      interleukin-2 (IL-2). Following this new approach, multiple TCRs were identified,
      synthesized, cloned into a retroviral vector, and then transduced into donor T
      cells. These transduced T cells were shown to specifically recognize the
      neoantigens presented by autologous APCs. In conclusion, this approach provides
      an efficient procedure to isolate neoantigen-specific TCRs for clinical
      applications, as well as for basic and translational research.

PMID- 29174844
TI  - Neuromuscular adaptations in older males and females with knee osteoarthritis
      during weight-bearing force control.
AB  - BACKGROUND: Females exhibit significantly greater incidence, prevalence, and
      severity of osteoarthritis (OA) compared to males. Despite known biological,
      morphological, and functional differences between males and females, there has
      been little sex-related investigation into sex-specific biomechanical and
      neuromuscular responses to OA. OBJECTIVE: To identify sex-related differences in
      OA-affected adults and within-sex differences between healthy and OA-affected
      adults' muscular activation patterns during lower limb loading. METHODS: Thirty
      adults with OA and 36 controls completed a standing ground reaction force (GRF)
      matching protocol requiring participants to expose equal body weight to each leg
      and modulate horizontal GRFs while maintaining constant joint positions.
      Electromyography was plotted as a function of GRF direction to depict muscle
      activation patterns. Muscles were classified as a general joint stabilizer,
      specific joint stabilizer or moment actuator by quantifying activation patterns
      with a test of asymmetry, specificity index and mean direction of activity. Lower
      limb kinematics and kinetics were also recorded. RESULTS: In general, muscle
      roles as it relates to joint stability did not differ between groups. Compared to
      controls, both males and females with OA demonstrated greater rectus femoris
      activity and reduced knee rotation moments. Females with OA had significantly
      greater biceps femoris and gastrocnemius activity during respective lateral, and
      anterior-medial loading directions compared to males with OA. CONCLUSIONS: We
      identified fundamental differences in muscular stabilization strategies in older
      adults with OA as well as sex-related changes in neuromuscular function that may
      influence joint loading conditions and provide insight into the greater incidence
      of knee OA in females.

PMID- 29174845
TI  - Impact of ventilation systems and energy savings in a building on the mechanisms
      governing the indoor radon activity concentration.
AB  - For a given radon potential in the ground and a given building, the parameters
      affecting the indoor radon activity concentration (IRnAC) are indoor
      depressurization of a building and its air change rate. These parameters depend
      mainly on the building characteristics, such as airtightness, and on the nature
      and performances of the ventilation system. This study involves a numerical
      sensitivity assessment of the indoor environmental conditions on the IRnAC in
      buildings. A numerical ventilation model has been adapted to take into account
      the effects of variations in the indoor environmental conditions
      (depressurization and air change rate) on the radon entry rate and on the IRnAC.
      In the context of the development of a policy to reduce energy consumption in a
      building, the results obtained showed that IRnAC could be strongly affected by
      variations in the air permeability of the building associated with the
      ventilation regime.

PMID- 29174846
TI  - Quantitative proteomics study of host response to virulent and attenuated
      pseudorabies virus infection in mouse brain.
AB  - Bartha, the pseudorabies virus (PRV) vaccine strain, is widely used in studies of
      neuronal circuit-tracing, due to its attenuated virulence and retrograde
      spreading. However, we know little regarding the molecular mechanisms of PRV
      infection and spreading between structurally connected neurons. In this study, we
      systematically analyzed the host brain proteomes after acute infection with PRV,
      attempting to identified the proteins involved in the processes. Mice were
      injected with PRV-Bartha and PRV-Becker (PRV-Bartha's wild-type parent strain) in
      the olfactory system, the proteomes of the brain and synaptosome were analyzed
      and compared at various infection intervals using mass spectrometry-based
      proteomics techniques. In all, we identified >100 PRV-infection regulated
      proteins at the whole-tissue level and the synaptosome level. While at whole
      tissue level, bioinformatics analyses mapped most of the regulations to the
      inflammation pathways, at the synaptosome level, most of those to synaptic
      transmission, cargo transport and cytoskeleton organization. We established
      regulated protein networks demonstrating distinct cellular regulation pattern
      between the global and the synaptosome levels. Moreover, we identified a series
      of potentially PRV-strain-specific regulated proteins with diverse biological
      functions. This study may provide new clues for molecular mechanisms for PRV
      infection and spread.

PMID- 29174848
TI  - [Back loss cover in orthopedic surgery by helical lumbar perforator flaps: About
      6 cases].
AB  - INTRODUCTION: The existence of voluminous paralumbar perforators allows a
      simplification of the coverage of the lumbar region. MATERIALS AND METHODS: The
      authors present a series about lumbar loss substance following orthopedic
      surgery, from 2012 to 2017. Coverage was provided by a fascio-cutaneous lumbar
      perforator flap. RESULTS: Six patients were operated with mean age of 62.3 years,
      with an average follow-up of 16 months (up 6 to 41 months). Substance losses were
      secondary to a carcinologic excision, to a radiodermitis excision and to four
      debridements after infection of the operative site. In five cases, the
      reconstruction was performed by one lumbar perforator flap, and in one case by
      two lumbar perforator flaps. The average size of the substance losses was 171.91
      cm2 (up 78 to 250 cm2). The average size of the flaps taken was 161 cm2 (up 50 to
      250 cm2). The donor site was self-closing without sequelae. The postoperative
      sequences were simple and marked by a single partial necrosis of a flap, with a
      favorable evolution after directed healing. The quality of the cover was good
      with excellent trophicity. CONCLUSION: Lumbar perforator helical fascio-cutaneous
      flaps are a reliable means of covering the loss of substances in the lumbar
      region. The use of these flaps makes it possible to avoid the taking of complex
      myo-cutaneous flaps, causing sequelae of the donor site in a location difficult
      to cover.

PMID- 29174847
TI  - Molecular pathology of total knee arthroplasty instability defined by RNA-seq.
AB  - Total knee arthroplasty (TKA) is a durable and reliable procedure to alleviate
      pain and improve joint function. However, failures related to flexion instability
      sometimes occur. The goal of this study was to define biological differences
      between tissues from patients with and without flexion instability of the knee
      after TKA. Human knee joint capsule tissues were collected at the time of primary
      or revision TKAs and analyzed by RT-qPCR and RNA-seq, revealing novel patterns of
      differential gene expression between the two groups. Interestingly, genes related
      to collagen production and extracellular matrix (ECM) degradation were higher in
      samples from patients with flexion instability. Partitioned clustering analyses
      further emphasized differential gene expression patterns between sample types
      that may help guide clinical interpretations of this complication. Future efforts
      to disentangle the effects of physical and biological (e.g., transcriptomic
      modifications) risk factors will aid in further characterizing and avoiding
      flexion instability after TKA.

PMID- 29174849
TI  - [The advantages in using cyanoacrylate glue over skin staples as a method of skin
      graft fixation in the pediatric burns population].
AB  - INTRODUCTION: Local postoperative care and burn wound management can present with
      a certain degree of difficulty in the pediatric population. While the use of skin
      staples as a method of skin graft fixation is a well-known, rapid and simple
      method, their removal can be painful and may necessitate some sedation or even
      general anesthesia. We studied in this article the advantages and economic value
      of using the cyanoacrylate glue as a fixation method for skin grafts. MATERIALS
      AND METHODS: A comparative study was carried out from 2012 to 2016. Hundred and
      eighteen infants with burns up to 5% of total body surface area were included in
      the study. Seventy-two infants had split thickness skin grafts fixed with skin
      staples. Forty-six infants had split thickness skin grafts fixed with
      cyanoacrylate glue. We compared the quality of graft, the sedation used during
      the first postoperative dressing, the length of hospital stay, the amount of glue
      used and the presence of complications. RESULTS: There is a difference between
      the two groups studied in terms of age and total burn surface area. The rate of
      graft take was 100% in both groups. The first postoperative dressing was carried
      out without the use of powerful analgesia in the cyanoacrylate group, while it
      was necessary to use general anesthesia in 64% of the skin staples group. The
      average length of stay in hospital after skin grafting was 4.9 days for the
      cyanoacrylate glue versus 6.5 days in the skin staples group. No complications
      were noted in the 2 groups. CONCLUSION: The use of cyanoacrylate glue allows
      rapid fixation of skin grafts and avoid general anesthesia for postoperative
      cares. Subsequently the length of hospital stay is reduced within 25%. The medico
      economic value of glue protocol is highly significant compared to skin staples,
      while having similar good results and without significant problems.

PMID- 29174850
TI  - Association Between Pepsin in the Saliva and the Subjective Symptoms in Patients
      With Laryngopharyngeal Reflux.
AB  - OBJECTIVES: Our study was designed to further evaluate the relationships between
      the saliva pepsin level and the symptoms and quality of life of patients with
      laryngopharyngeal reflux (LPR). STUDY DESIGN: A prospective cohort study without
      controls. SETTING: Tertiary teaching hospital. SUBJECTS AND METHODS: We analyzed
      50 patients diagnosed with LPR by 24-hour multichannel intraluminal impedance pH
      monitoring. All subjects were instructed to collect saliva samples upon waking in
      the morning. The saliva pepsin levels were analyzed using enzyme-linked
      immunosorbent assay. The Reflux Symptom Index, Reflux Finding Score,
      Laryngopharyngeal Reflux-Health-Related Quality of Life, and Short Form 36 survey
      were administered. RESULTS: The pepsin was detected in the saliva of 41 patients
      with LPR (17.15 +/- 20.42 ng/mL). Nine patients did not have pepsin in the
      saliva. There were no significant associations between the pepsin level in the
      saliva and Reflux Symptom Index, Laryngopharyngeal Reflux-Health-Related Quality
      of Life, or Short Form 36 of patients with LPR. CONCLUSION: The saliva pepsin
      level is not significantly correlated with LPR symptoms or quality of life in LPR
      patients. It may be true that there is no association between pepsin levels and
      LPR symptoms, but this lack of association does not prove the lack of
      pathophysiological effect.

PMID- 29174851
TI  - Hepatoprotective effect of quercetin via TRAF6/JNK pathway in acute hepatitis.
AB  - Quercetin, as a member of the flavonoids family, has many beneficial properties.
      The aim of our study was to evaluate the protective effect of quercetin in ConA
      induced hepatitis in mice, and to clarify its mechanism of action. Hepatitis was
      induced by using ConA (25 mg/kg), and quercetin was administered intragastrically
      at the dose of 100 mg/kg or 200 mg/kg for 5 days before ConA injection. The serum
      levels of liver enzymes, inflammatory cytokines and other marker proteins were
      determined at 2 h, 8 h and 24 h after ConA injection. Following ConA injection,
      serum levels of liver enzymes and inflammatory cytokines were significantly
      increased. Quercetin ameliorated liver damage and histopathological changes, and
      suppressed the release of inflammatory cytokines. The expression of Bax, Bcl-2,
      Beclin-1, LC3, P62 and caspase 9 were markedly affected by quercetin
      pretreatment. The expression of TRAF6 and p-JNK were decreased in the quercetin
      groups. Quercetin attenuated apoptosis and autophagy in ConA-induced autoimmune
      hepatitis by inhibiting TRAF6/JNK pathway.

PMID- 29174853
TI  - Inonotus obliquus extract induces apoptosis in the human colorectal carcinoma's
      HCT-116 cell line.
AB  - Because of irregular dietary habits and lifestyle in Taiwan, the incidence and
      mortality rate of colorectal cancer have been increasing rapidly these years.
      This study investigated the inhibitory activity against the proliferation of
      human colorectal cancer HCT-116 cells by Inonotus obliquus extracts obtained from
      submerged fermentation. Cell viability was measured by the reduction of MTT and
      cell membrane integrity was determined by lactic dehydrogenase (LDH) release. The
      mRNA expression of proapoptosis and antiapoptosis mediators was assayed by real
      time PCR, and the levels of p53 and NF-kappaB p65 were assessed using Western
      blot analysis. Furthermore, the influences of I. obliquus extracts to HCT-116
      cells were evaluated by caspase-3 activity. The results can be summarized as, for
      the mitochondrial apoptotic pathway, quantitative RT-PCR data showed up
      regulation of proapoptotic genes (Bax, bad, and caspase-3) and increased Bax/bcl
      2 ratio by I. obliquus extracts. Moreover, treating with 20 mg/mL I. obliquus
      extracts augmented caspase-3 activity in HCT-116 cells. Induction of cell cycle
      G0/G1 phase arrest: I. obliquus extracts up-regulated the mRNA expression of
      proapoptotic genes (p53, p21WAF1/CIP1) and down-regulated antiapoptotic gene
      (CyclinD1), while extracts of I. obliquus mycelia increased the expressions of
      p53 protein in HCT-116 cells. I. obliquus extracts decreased the expression of NF
      kappaB p65 protein and COX-2 gene in HCT-116 cells. Taking together, I. obliquus
      extracts may be used as a potentially novel food material for health care to
      improve the treatment of colorectal cancer.

PMID- 29174852
TI  - Activation of Epac alleviates inflammation and vascular leakage in LPS-induced
      acute murine lung injury.
AB  - Exchange protein directly activated by cAMP (Epac) is an important molecule in
      cAMP signal transduction, but the effect of Epac on lipopolysaccharide (LPS)
      induced acute lung injury (ALI) is unclear. In this study, we treated in vitro
      and in vivo models with the Epac activator 8CPT to determine the effect and
      related mechanisms of Epac. The in vitro results indicate that 8CPT inhibits
      lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release
      from mouse macrophages (MH-S), whereas the protein kinase A (PKA) activator 6BnZ
      has no effect. Furthermore, Epac over-expression can significantly suppress TNF
      alpha release from LPS induced MH-S cell, while Epac siRNA can slightly increase
      TNF-alpha release. Moreover, 8CPT reduces LPS-induced microvascular permeability
      in human pulmonary microvascular endothelial cells (HPMVECs), whereas the PKA
      activator 6BnZ has no effect. In mice with LPS-induced ALI, 8CPT significantly
      reduces LPS-induced inflammatory cytokine release, neutrophil recruitment, and
      albumin leakage. LPS simultaneously decreases the Epac but not the PKA levels.
      However, 8CPT reverses the decreased Epac levels. Furthermore, the mechanism
      involves the small GTPase Rac1/2 but not the mitogen-activated protein kinase
      (MAPK) pathway. Thus, Epac activation reduces inflammation and microvascular
      permeability in LPS-induced lung injury and an Epac activator represents a novel
      choice for the early therapy of ALI.

PMID- 29174854
TI  - DUSP19 regulates IL-1beta-induced apoptosis and MMPs expression in rat
      chondrocytes through JAK2/STAT3 signaling pathway.
AB  - Osteoarthritis (OA) is a disease with degeneration of articular cartilage and its
      development and progression is characterized by chondrocyte apoptosis. To examine
      whether DUSP19 and inhibitor of the JAK2/STAT3 will influence the response of rat
      chondrocytes cultured with IL-1beta. Dose-response studies were conducted under
      IL-1beta conditions. In separate experiments, chondrocytes were treated with an
      appropriate concentration of IL-1beta with either DUSP19-expressing constructs or
      AG490, whereas chondrocytes were also treated with DUSP19-RNA interference
      constructs with or without AG490. The expression of DUSP19, apoptosis markers,
      JAK2/STAT3 and phosphorylation of JAK2/STAT3 was measured by Real-time PCR and/or
      western blot assay. CCK-8 assay and Annexin V/propidium iodide staining was used
      to detect chondrocyte viability and apoptosis, respectively. IL-1beta dose
      dependently decreased the expression of DUSP19 and the viability of chondrocytes.
      Chondrocytes with DUSP19 up-regulation inhibited IL-1beta-induced increases in
      the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 expression as well as cell apoptosis.
      However, DUSP19 down-regulation mimicked the effect of IL-1beta on JAK2/STAT3
      activity and chondrocyte apoptosis. AG490 inhibited JAK2/STAT3 activation as well
      as apoptosis in chondrocytes induced by IL-1beta or DUSP19 down-regulation,
      evidenced by decreased expression of Bax, Caspase-3 and increased Bcl-2
      expression as well as MMP-3, -9 and -13 expressions. Taken together, our results
      demonstrate that DUSP19 up-regulation inhibited IL-1beta-induced chondrocytes
      apoptosis and MMPs expression through inactivating JAK2/STAT3 pathway.

PMID- 29174855
TI  - Simulating uni- and bi-directional pedestrian movement on stairs by considering
      specifications of personal space.
AB  - This paper presents an enhanced model that considers the specifications of
      personal space to describe uni- and bi-directional pedestrian movement on stairs.
      The shape of the personal space of each pedestrian is regarded as an oval shape,
      which is composed of four arcs, to precisely quantify movements. Specific models
      that facilitate the simulation of movement include adjustments to individual
      speeds based on the proximity of other members, conflict avoidance, overtaking,
      and direction finding. By implementing these parameters in the simulation, basic
      data concerning these movement behaviours were collected from the experiment,
      which was carried out at one a Shanghai subway station. Twenty-four young college
      students participated in this experiment. Numerical simulation results for a
      stochastic case under those parameters were obtained. The fundamental diagrams
      and moving behaviours according to different proportions of ascending and
      descending pedestrians are analysed and discussed. The results indicate that the
      simulation platform for personal space can serve as a useful tool to evaluate
      pedestrian movement on stairs.

PMID- 29174856
TI  - The Child Neurology Trainee-as-Teacher: A Clinical Teaching Curriculum Tailored
      to Learners' Needs and Developmental Roles.
AB  - BACKGROUND: Clinical teaching skills programs for resident physicians are
      increasingly offered. Less attention has been devoted to the unique educational
      roles of specialty residents and subspecialty fellows, many of whom will become
      academic faculty physicians. These teaching roles, and therefore a trainee's
      learning needs and motivation, also change over the course of training. METHODS:
      We designed and implemented a two-year longitudinal teaching curriculum for child
      neurology and neurodevelopmental disabilities residents using adult learning
      theory principles: experiential learning and immediate applicability to specific
      roles. Core modules included teaching in clinical settings, adult learning, and
      giving feedback. Training-year-specific modules for second-year residents (n =
      11) and final-year residents (n = 10) included teaching through consultation and
      promoting clinical reasoning in supervisory roles. Learners completed an 11-item
      self-assessment before and after intervention. RESULTS: The overall program
      significantly increased residents' self-assessed knowledge of how to assess the
      level of a learner (P = 0.02, Cohen d = 0.84) and comfort and skill in giving
      feedback (P = 0.04, d = 0.64; P = 0.04, d = 0.71). The final-year-specific
      curriculum additionally increased self-assessed skill in teaching same-specialty
      residents (P = 0.05, d = 1.07) and in promoting clinical reasoning (P = 0.03, d =
      1.14). The program was rated highly by trainees and faculty, and has been adopted
      as an ongoing part of our training program. CONCLUSIONS: Our experience offers a
      reproducible model and theoretical framework for child neurology,
      neurodevelopmental disabilities, and other specialty programs to develop
      customized trainee-as-teacher curricula with specialty- and training-year
      specific content.

PMID- 29174857
TI  - The Utility of Collaterals as a Biomarker in Pediatric Unilateral Intracranial
      Arteriopathy.
AB  - BACKGROUND: Intracranial arteriopathies are frequent causes of pediatric stroke
      and important risk factors for stroke recurrence. Without tissue diagnosis,
      vascular imaging is relied upon to identify the underlying etiology and
      prognosis. We hypothesized that children with unilateral intracranial
      arteriopathy with lenticulostriate collaterals would demonstrate distinct
      vascular outcomes compared with children without collaterals. METHODS: We
      retrospectively identified children with unilateral intracranial arteriopathy
      from two institutions. Two blinded raters from each institution reviewed magnetic
      resonance or digital subtraction angiography at baseline and >=12 months.
      Patients were grouped according to presence or absence of lenticulostriate
      collaterals. Clinical features and vascular imaging outcomes were compared using
      univariate analysis and multivariate logistic regression. RESULTS: Forty-four
      children were included: 22 males, median age 8.2 years (range two to 16.9 years),
      and further stratified into the collateral group (n = 20) and non-collateral
      group (n = 24), with median follow-up of 25.5 months and 23 months, respectively.
      Both groups demonstrated similar rates of progression on vascular imaging at >=12
      months, 50% in the collateral group versus 37.5% in the non-collateral group (P >
      0.05). The collateral group was associated with asymptomatic clinical
      presentation, normal brain MRI, border zone infarcts, and either vascular
      stabilization or new contralateral disease. The non-collateral group demonstrated
      either vascular improvement or discordant progression (combination of improved
      and progressive lesions). Using a multivariate model, collaterals continued to be
      an independent predictor of vascular outcome. CONCLUSIONS: This study suggests
      that lenticulostriate collaterals in children with unilateral intracranial
      arteriopathy may serve as a useful neuroimaging biomarker that helps to stratify
      patients with distinct clinical features and patterns of vascular evolution.

PMID- 29174858
TI  - Visualized Evaluation of Blood Flow to the Gastric Conduit and Complications in
      Esophageal Reconstruction.
AB  - BACKGROUND: Evaluation of the blood supply to gastric conduits is critically
      important to avoid complications after esophagectomy. We began visual evaluation
      of blood flow using indocyanine green (ICG) fluorescent imaging in July 2015, to
      reduce reconstructive complications. In this study, we aimed to statistically
      verify the efficacy of blood flow evaluation using our simplified ICG method.
      STUDY DESIGN: A total of 285 consecutive patients who underwent esophagectomy and
      gastric conduit reconstruction were reviewed and divided into 2 groups: before
      and after introduction of ICG evaluation. The entire cohort and 68 patient pairs
      after propensity score matching (PS-M) were evaluated for clinical outcomes and
      the effect of visualized evaluation on reducing the risk of complication.
      RESULTS: The leakage rate in the ICG group was significantly lower than in the
      non-ICG group for each severity grade, both in the entire cohort (285 subjects)
      and after PS-M; the rates of other major complications, including recurrent
      laryngeal nerve palsy and pneumonia, were not different. The duration of
      postoperative ICU stay was approximately 1 day shorter in the ICG group than in
      the non-ICG group in the entire cohort, and approximately 2 days shorter after PS
      M. Visualized evaluation of blood flow with ICG methods significantly reduced the
      rate of anastomotic complications of all Clavien-Dindo (CD) grades. Odds ratios
      for ICG evaluation decreased with CD grade (0.3419 for CD >= 1; 0.241 for CD >=
      2; and 0.2153 for CD >= 3). CONCLUSIONS: Objective evaluation of blood supply to
      the reconstructed conduit using ICG fluorescent imaging reduces the risk and
      degree of anastomotic complication.

PMID- 29174859
TI  - Management of hypogammaglobulinemia and recurrent infections in a chronic
      lymphocytic leukemia patient receiving ibrutinib.

PMID- 29174860
TI  - Ageism and suicide prevention.

PMID- 29174861
TI  - Evaluation of saliva and plasma cytokine biomarkers in patients with oral
      squamous cell carcinoma.
AB  - The aim of this study was to investigate potential biomarkers in human saliva and
      plasma to aid in the early diagnosis of oral squamous cell carcinoma (OSCC).
      Saliva and plasma samples obtained from OSCC patients (n=41) and non-oral cancer
      patients (n=24) were analyzed by Luminex Bead-based Multiplex Assay. Data were
      analyzed using the non-parametric Mann-Whitney U-test, Kruskal-Wallis test, and
      receiver operating characteristics curve (ROC) to evaluate the predictive power
      of 14 biomarkers individually for OSCC diagnosis. The plasma level of IP-10 in
      early OSCC differed significantly from that in controls. Among the salivary
      biomarkers, IL-1beta, IL-6, IL-8, MIP-1beta, eotaxin and IFN-gamma and TNF-alpha
      showed significant differences between OSCC patients and controls. With respect
      to carcinogenesis, significant differences in plasma levels of eotaxin, G-CSF,
      and IL-6 were found between OSCC stages III/IV and OSCC stages I/II. The area
      under the curve (AUC) for OSCC vs. control was greater than 0.7 for plasma IP-10
      and saliva IL-1beta, IL-6, IL-8, and TNF-alpha. The study findings indicate that
      salivary biomarkers may serve a useful role as a complementary adjunct for the
      early detection of oral OSCC. With regard to the evaluation of tumour
      progression, plasma eotaxin, G-CSF, and IL-6 may help in the detection of
      advanced OSCC. However, the correlation between saliva and plasma biomarkers in
      OSCC was weak.

PMID- 29174862
TI  - Clinical implications of taste thresholds in patients with odontogenic maxillary
      sinusitis.
AB  - Patients with odontogenic maxillary sinusitis (OMS) often complain of reduced
      taste sensitivity as well as nasal obstruction. The filter paper disc method (the
      conventional gustatory test) was applied to nine patients who underwent sinus
      surgery to open the inferior nasal meatus and sinus drainage, on three different
      days: 1day prior to surgery, 7days postoperative, and 28days postoperative. The
      same test was applied to nine non-clinical participants with or without clipping
      the nose to interfere with smooth nasal airflow on two different days. Acquired
      recognition thresholds for the four basic tastes of sweet, salty, sour, and
      bitter were assessed. In OMS patients, the recognition thresholds for all four
      tastes were markedly decreased at 7 and 28days postoperative, and subjective
      taste sensitivity and the elimination of nasal obstruction was improved. The mean
      recognition threshold for the four tastes correlated negatively with taste
      satisfaction scores. Clipping the nose in non-clinical participants induced
      increases in gustatory detection and recognition thresholds. Despite the small
      sample size and different ages and sexes of the study subjects, it was
      demonstrated that nasal obstruction in OMS patients and nose clipping in non
      clinical subjects reduce taste reactivity, and surgical intervention to promote
      nasal airflow recovers impaired taste reactivity.

PMID- 29174863
TI  - Adolescent environmental enrichment prevents the emergence of schizophrenia-like
      abnormalities in a neurodevelopmental model of schizophrenia.
AB  - In the present study, we investigated whether exposure to an enriched environment
      (EE) during adolescence might affect the behavioural dysfunction (sensorimotor
      gating deficit, memory and social interaction impairments) and neurochemical
      changes (GAD67 expression, histone methylation) induced by methylazoxymethanol
      (MAM) in the MAM-E17 rat model of schizophrenia. EE was introduced for 7 days in
      early adolescence (days 23-29), and behavioural and biochemical studies were
      performed on adult rats at postnatal day 70. The results showed that exposure to
      EE prevented the development of adult behavioural deficits induced by prenatal
      MAM administration. EE also prevented the decrease in GAD67 mRNA and protein
      levels induced by MAM in the medial prefrontal cortex (mPFC). Moreover, EE
      inhibited the reductions in the amount of Gad1 bound to H3K4me3 and in the total
      H3K4me3 protein level induced by prenatal MAM administration in the adult mPFC.
      However, there was no effect of EE on behaviour or levels of the various
      neurochemical markers in adult rats prenatally treated with vehicle. Thus, these
      results indicate that EE exposure during early adolescence may inhibit the
      development of schizophrenia related symptoms through epigenetic mechanisms that
      regulate the expression of genes (e.g., Gad1) that are impaired in schizophrenia.

PMID- 29174864
TI  - A multi-centre, randomised, double-blind, placebo-controlled clinical trial of
      methylphenidate in the initial treatment of acute mania (MEMAP study).
AB  - : Based on many clinical and preclinical findings the 'vigilance regulation model
      of mania' postulates that an unstable regulation of wakefulness is a pathogenetic
      factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and
      induces hyperactivity and sensation seeking as an autoregulatory attempt to
      stabilize wakefulness. Accordingly, stimulant medications with their vigilance
      stabilizing properties could have rapid antimanic effects similar to their
      beneficial effects in ADHD. The MEMAP study - a multi-center, double-blind,
      placebo-controlled and randomized clinical trial (RCT) - assessed the antimanic
      efficacy and safety of a 2.5-day treatment with methylphenidate (20-40mg/day). Of
      157 screened patients with acute mania, 42 were randomly assigned to receive 20
      40mg per day of methylphenidate in one or two applications, or placebo. The
      primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from
      baseline to day 2.5 in the methylphenidate group compared to the placebo group. A
      group sequential design was chosen to justify early RCT termination based on
      efficacy or futility at an interim analysis after inclusion of 40 patients. In
      the interim analysis, the change from baseline in the YMRS total score at day 2.5
      was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus,
      futility was declared for methylphenidate and the RCT was stopped. In summary,
      although methylphenidate was well tolerated and safe in the full analysis set, it
      failed to show efficacy in the treatment of acute mania. TRIAL REGISTRATION:
      clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number:
      NCT01541605).

PMID- 29174865
TI  - Deep brain stimulation induces antidepressant-like effects in serotonin
      transporter knockout mice.
AB  - BACKGROUND: Some of the antidepressant-like effects of ventromedial prefrontal
      cortex (vmPFC) deep brain stimulation (DBS) in rodents have been attributed to
      the modulation of prefrontal-raphe pathways. This is largely different from
      selective serotonin reuptake inhibitors (SSRIs), which increase serotonin (5-HT)
      levels by inhibiting the serotonin transporter (SERT). SSRIs have limited
      efficacy when given to SERT knockout (KO) mice, or patients with mutations in the
      serotonin transporter promoter gene (5-HTTLPR). HYPOTHESIS: vmPFC DBS will induce
      antidepressant-like effects and serotonin release in SERT KOs. RESULTS: DBS
      treated wild-type and SERT KO mice had a significant 22-26% decrease in
      immobility in the forced swim test. DBS delivered to either group was associated
      with 33-55% increase in 5-HT levels. CONCLUSIONS: DBS induced a significant
      antidepressant-like effect in KO mice. This suggests that it may be reasonable to
      consider DBS in states where SERT is not fully operational.

PMID- 29174866
TI  - Acute Myocardial Infarction Population Incidence and Mortality Rates, and 28-day
      Case-fatality in Older Adults. The REGICOR Study.
AB  - INTRODUCTION AND OBJECTIVES: Our aims were to determine acute myocardial
      infarction (AMI) incidence and mortality rates, and population and in-hospital
      case-fatality in the population older than 74 years; variability in clinical
      characteristics and AMI management of hospitalized patients, and changes in the
      incidence and mortality rates, case-fatality, and management by age groups from
      1996 to 1997 and 2007 to 2008. METHODS: A population-based AMI registry in Girona
      (Catalonia, Spain) including individuals with suspected AMI older than 34 years.
      RESULTS: The incidence rate increased with age from 169 and 28 cases/100 000 per
      year in the group aged 35 to 64 years to 2306 and 1384 cases/100 000 per year in
      the group aged 85 to 94 years, in men and women, respectively. Population case
      fatality also increased with age, from 19% in the group aged 35 to 64 years to
      84% in the group aged 85 to 94 years. A lower population case-fatality was
      observed in the second period, mainly explained by a lower in-hospital case
      fatality. The use of invasive procedures and effective drugs decreased with age
      but increased in the second period in all ages up to 84 years. CONCLUSIONS: Acute
      myocardial infarction incidence, mortality, and case-fatality increased
      exponentially with age. There is still a gap in the use of invasive procedures
      and effective drugs between younger and older patients.

PMID- 29174867
TI  - The synthesis of steroids by Taenia crassiceps WFU cysticerci and tapeworms is
      related to the developmental stages of the parasites.
AB  - Taeniids tapeworms are hermaphroditic helminths that gradually develop testis and
      ovaries in their reproductive units. The larval stage of the tapeworms named
      cysticercus is a vesicle that contains the scolex and proliferates asexually in
      the abdominal cavity of mice. Once in the host, they evaginate, attach to the gut
      and develop into an adult organism, the tapeworm. We have previously reported
      reported that T. crassiceps ORF and solium cysticerci transform steroid
      precursors to androgens and estrogens. Taenia crassiceps WFU cysticerci can also
      synthesize corticosteroids. The aim of the present work is to investigate the
      relationship between steroid synthesis ability and the developmental stage of the
      parasite T. crassiceps WFU. To this purpose, cysticerci were obtained from the
      abdominal cavity of female mice, manually separated in invaginated (IC) and
      evaginated parasites (EC) and preincubated for 24 h in DMEM plus
      antibiotics/antimycotics. Next step consisted in incubation for different periods
      in the fresh media added with tritiated androstenedione (3H-A4) or progesterone
      (3H-P4) and incubated for different periods. Taenia crassiceps WFU tapeworms were
      recovered from the intestine of golden hamsters that had been orally infected
      with cysticerci. The worms were pre-cultured in DMEM plus FBS and antibiotics,
      and then incubated without FBS for different time periods, in the presence of 3H
      A4 or 3H-P4. At the end of the experiments the media from cysticerci and
      tapeworms were analyzed by thin layer chromatography. Results showed that
      testosterone synthesis was significantly higher in the evaginated cysticerci and
      increased with time in culture. The invaginated and evaginated cysticerci also
      synthesized small quantities of 17beta-estradiol (E2) and estrone. The evaginated
      cysticerci synthesized twice more 3H-deoxycorticosterone (3H-DOC) than the
      invaginated parasites, the production increased significantly with time in
      culture. Taenia crassiceps WFU tapeworms synthesized significant quantities of 3H
      testosterone and small amounts of estrone after only 3 h of culture in the
      presence of 3H-A4. The tapeworms also transformed 3H-P4 to 3H-DOC and increased
      its synthesis after 24 h in culture. In summary, our data show the pathways that
      T. crassiceps WFU cysticerci use to synthesize sexual steroids in both larval
      developmental stages and reveals the steroidogenic capacity of the tapeworms.

PMID- 29174868
TI  - Expression of gonadotropin and sex steroid hormone receptor mRNA in the utero
      vaginal junction containing sperm storage tubules of oviduct during sexual
      maturation in Japanese quail.
AB  - Sex steroid hormones play an important role in reproductive tissue development of
      avian species. However, their role in Japanese quail is yet to be established. To
      understand the physiological role of hormones involved in the development of
      sperm storage tubules (SSTs) in quail, we investigated expression profiles of
      gonadotropin (LH-R and FSH-R) and sex steroid hormone (PR-R, ER-alpha and ER
      beta) receptors in the uterovaginal junction (UVJ) containing SSTs before and
      during sexual maturation i.e. four to eight weeks. Every week four birds were
      sacrificed to collect blood and UVJ for sex steroid hormone (progesterone and
      estrogen) estimation and gene expression profiling of sex steroid hormone (PR-R,
      ER-alpha and ER-beta) and gonadotropin receptors (LH-R and FSH-R) using qRT-PCR.
      Receptor expression results showed that the expression of sex steroid receptor
      (PR-R, ER-alpha and ER-beta) genes were upregulated significantly (P < .05) in
      SSTs with the advancement of age. The expression of gonadotropin receptors (LH-R
      and FSH-R) was only high at week 5 and 6 respectively. Serum hormone analysis
      indicated a significant (P < .05) rise in estradiol till 7th week and
      progesterone from 7th week onwards. These results suggest that the gonadotropin
      and sex steroid hormone receptors may have the role in the development and
      maintenance of UVJ that contains predominantly SSTs during sexual maturation.

PMID- 29174869
TI  - Expression characteristics of BMP2, BMPR-IA and Noggin in different stages of
      hair follicle in yak skin.
AB  - Bone morphogenetic protein 2 (BMP2), BMP receptor-IA (BMPR-IA), and the BMP2
      antagonist Noggin are important proteins involved in regulating the hair follicle
      (HF) cycle in skin. In order to explore the expression profiles of BMP2, BMPR-IA,
      and Noggin in the HF cycle of yak skin, we collected adult yak skin in the
      telogen, proanagen, and midanagen phases of HFs and evaluated gene and protein
      expression by real-time quantitative polymerase chain reaction (qRT-PCR), western
      blotting, and immunohistochemistry. qRT-PCR and western blotting results showed
      that BMP2 and BMPR-IA expression levels were highest in the telogen of HFs and
      higher than that of Noggin in the same phase. The expression of Noggin was
      significantly higher in proanagen and midanagen phases of HFs than in the telogen
      phase, with the highest expression observed in the proanagen phase. Moreover, the
      expression of Noggin in the proanagen phase was significantly higher than those
      of BMP2 and BMPR-IA during the same phase. Immunohistochemistry results showed
      that BMP2, BMPR-IA, and Noggin were expressed in the skin epidermis, sweat
      glands, sebaceous glands, HF outer root sheath, and hair matrix. In summary, the
      characteristic expression profiles of BMP2, BMPR-IA, and Noggin suggested that
      BMP2 and BMPR-IA had inhibitory effects on the growth of HFs in yaks, whereas
      Noggin promoted the growth of yak HFs, mainly by affecting skin epithelial cell
      activity. These results provide a basis for further studies of HF development and
      cycle transition in yak skin.

PMID- 29174870
TI  - Molecular cloning, tissue distribution, and effect of fasting and refeeding on
      the expression of neuropeptide Y in Channa argus.
AB  - Neuropeptide Y (NPY) is a 36 amino-acid amidated peptide of the pancreatic
      polypeptide (PP) family, which plays an important role in appetite regulation and
      energy expenditure in mammals. Although several teleost NPY have been identified,
      its roles remain unclear in fish. We herein reported on the molecular cloning,
      tissue distribution and the effect of fasting on the expression of NPY in Channa
      argus, and designated as CaNPY. It consisted of a 300 bp open reading frame
      predicted to encode a prepro-NPY of 99 amino acids. Sequence analysis revealed
      that CaNPY was highly conserved (>60%) with other vertebrate NPY. Phylogenetic
      analysis highly supported CaNPY was closely related to piscine NPY. In addition,
      except for muscle and spleen tissues, CaNPY was found to extensively expressed in
      all other detected tissues, with the highest level in brain. Futhermore, the
      CaNPY transcript was found to significantly increase after short-term and long
      term food deprivation, and dramatically decrease following refeeding. These
      findings suggested that CaNPY might be involved in food intake regulation and it
      could be as a potential target locus to improve commercial production of this
      kind of fish.

PMID- 29174871
TI  - Resection of neurogenic heterotopic ossification (NHO) of the hip.
AB  - Neurogenic heterotopic ossification of the hip is secondary to neurologic lesions
      such as cranial trauma, stroke, medullary injury or cerebral anoxia. We shall not
      deal here with the other etiologies of heterotopic ossification. There are
      numerous locations within the hip, depending on etiology and relations with
      adjacent neurovascular structures are sometimes close. Preoperative work-up
      should include contrast-enhanced CT; scintigraphy is non-contributive.
      Indications for surgery are decided in a multidisciplinary team meeting, with a
      contract laying out expected functional gain. It is this contract that determines
      the extent of resection, without seeking complete resection, which would incur an
      increased risk of complications. The surgical approach and resection strategy
      depend on lesion location and any resulting neurovascular compression. The most
      common complications are infection and postoperative hematoma. No adjuvant
      treatments have demonstrated efficacy against recurrence.

PMID- 29174872
TI  - Monteggia injuries.
AB  - The Monteggia injury is defined as radial head dislocation with a fracture of the
      ulnar shaft. This combination should be sought routinely in patients with ulnar
      fractures, even when the displacement is small. The emergent management is
      simple, as reducing the ulnar fracture is usually sufficient to stabilise the
      radial head. Internal fixation of the ulna deserves to be widely used to fully
      stabilise the radial head. Irreducibility of the radial head at the acute stage
      may indicate an interposition, which requires open surgery on the joint. Radial
      head dislocation may occur even with minimal displacement of the ulnar fragment.
      Chronic Monteggia fractures are more challenging to treat and their outcomes are
      more variable. The radial head becomes irreducible after 2 to 3 weeks. When a
      simple surgical approach fails to ensure stable reduction, the most widely used
      method at present is open reduction of the radial head and proximal osteotomy of
      the ulnar shaft. Stability must be obtained intra-operatively. Without treatment,
      radial head dislocation may be well tolerated for several months or even years.
      In the long term, however, osteoarticular remodelling results in loss of joint
      congruence, pain and, eventually, osteoarthritis. Radiographs must therefore be
      obtained on an emergency basis and analysed with great care to avoid missing a
      Monteggia fracture.

PMID- 29174873
TI  - Oral Sex and Condom Use in a U.S. National Sample of Adolescents and Young
      Adults.
AB  - PURPOSE: The objective of this study was to examine correlates associated with
      condom use at the last oral sex, as well as oral sex behavior, among adolescents
      and young adults (AYAs) aged 15-24 years in the U.S. METHODS: Descriptive
      statistics, logistic regression, and multinomial logistic regression were
      conducted using data collected from 3,816 females and 3,520 males in the 2011
      2015 National Survey of Family Growth. RESULTS: More than half of AYAs had
      engaged in oral sex with an opposite-sex partner. Most youth reported having at
      least one oral sex partner in the last 12 months, with 16% of females and 24% of
      males reporting two or more partners. Condom use at the last oral sex was quite
      low (8% for females and 9% for males). Black males (adjusted odds ratio [AOR] =
      3.46), black females (AOR = 2.65), and females of other race/ethnicities (AOR =
      2.40) were more likely to use a condom at the last oral sex. Females aged 20-24
      years (AOR = .31), females whose mothers had a college education or more (AOR =
      .43), and males and females who reported no intercourse experience were less
      likely to use a condom at the last oral sex (AORs = .46 and .20, respectively).
      CONCLUSIONS: Our study suggests that oral sex with an opposite-sex partner is a
      normative behavior for AYAs; however, condom use during this sexual activity is
      uncommon. Interactive workshops and physician-patient discussions focused on the
      health risk risks associated with oral sex, as well as appropriate methods of
      protection, may help to increase condom uptake.

PMID- 29174874
TI  - Cervical Cancer Screening and Follow-Up Procedures in Women Age <21 Years
      Following New Screening Guidelines.
AB  - PURPOSE: The 2009 American College of Obstetricians and Gynecologists guidelines
      recommended no cervical cancer screening before age 21 years. We examined changes
      in screening, diagnostic, and treatment procedures for cervical dysplasia after
      guideline introduction, and cost implications. METHODS: We studied Davidson
      County women aged 18-20 years, enrolled in Tennessee Medicaid, 2006-2014. We
      identified those with at least one Papanicolaou (Pap) test, human papillomavirus
      detection test, colposcopy, or excisional dysplasia treatment annually via
      Current Procedural Terminology coding. We used rate ratios with 95% confidence
      intervals to compare annual changes in procedure and treatment rates from 2014 to
      2006. We counted total outcomes to estimate annual costs based on 2014 average
      procedural costs. RESULTS: From 2006 to 2014, about 3,800 Davidson County women
      aged 18-20 years were enrolled in Medicaid annually. From 2006 to 2014, there
      were declines in Pap tests from 55.6 to 15.2 per 100 women (rate ratio .27, 95%
      confidence interval .25-.3); human papillomavirus tests from 13.8 to 5.9 per 100
      (.42, .36-.5); colposcopy from 9.4 to 1.1 per 100 (.12, .08-.17); and dysplasia
      treatment from 1.1 to 0 per 100. The estimated cost of screening and procedures
      fell from $53 to $8 per enrolled woman, not accounting for changes in visits or
      complications associated with these procedures. CONCLUSIONS: The 2009 screening
      guidelines were associated with major declines in screening, diagnostic, and
      treatment procedures for cervical dysplasia. Minimum estimated procedure and
      treatment costs saved were $45 per enrolled woman age 18-20 years.

PMID- 29174875
TI  - Insights Into Aspects Behind Internet-Related Disorders in Adolescents: The
      Interplay of Personality and Symptoms of Adjustment Disorders.
AB  - PURPOSE: Problematic Internet use (PIU) that has recently been referred to as
      Internet-related disorder is a growing health concern. Yet, it is unclear why
      some adolescents are developing problematic use, whereas others sustain control.
      Based on previous research, we hypothesize that personality traits (low
      conscientiousness and high neuroticism) act as predispositions for PIU. We
      further hypothesize that PIU can be understood as a maladaptive reaction toward
      critical life events and that these maladaptive reactions are exacerbated by
      dysfunctional personality traits. METHODS: The study investigates the prevalence
      of distinct subtypes of PIU among a sample of adolescents (n = 1,489; 10-17
      years). Personality traits (Big Five Inventory-10 [BFI-10]), perceived stress
      (Perceived Stress Scale 4 [PSS-4]), and their relations to PIU (Scale for the
      Assessment of Internet and Computer Game Addiction [AICA-S]) were examined. As
      novel research questions, associations between PIU and adjustment disorders
      (Adjustment Disorder-New Module [ADNM]-6) and the mediating role of personality
      were investigated. RESULTS: The prevalence of PIU was 2.5%; girls (3.0%) were
      more often affected than boys (1.9%). Social networking sites in girls and online
      games in boys were most often associated with PIU. Low conscientiousness and high
      neuroticism generally predicted PIU. Significantly more adolescents with PIU
      (70%) reported critical life events compared with those without PIU (42%). PIU
      was related to heightened stress and higher adjustment disorder symptoms. These
      associations were exacerbated by conscientiousness and neuroticism. CONCLUSIONS:
      Although the overall prevalence for PIU is in line with previous studies, it
      appeared unexpectedly that girls were affected more often than boys. Adjustment
      disorders and stress showed strong associations with PIU. This bears implications
      for adapting etiopathological assumptions and early intervention strategies.

PMID- 29174876
TI  - Ability of Nontraditional Risk Factors and Inflammatory Biomarkers for
      Cardiovascular Disease to Identify High Cardiometabolic Risk in Adolescents:
      Results From the LabMed Physical Activity Study.
AB  - PURPOSE: Then objective of this study was to evaluate the ability of several
      nontraditional cardiometabolic and inflammatory biomarkers in identifying high
      cardiometabolic risk in adolescents. METHODS: A cross-sectional study was
      conducted with 529 Portuguese adolescents (267 girls) aged 14.3 +/- 1.7 years. A
      clustered cardiometabolic risk score (body fat percentage, systolic blood
      pressure, ratio of total cholesterol to high-density lipoprotein cholesterol,
      triglycerides, homeostatic model assessment of insulin resistance, and negative
      values of cardiorespiratory fitness) was computed. The nontraditional
      cardiometabolic biomarkers assessed were complement factors (C3 and C4), C
      reactive protein (CRP), fibrinogen, leptin, white blood cells (WBCs), albumin,
      interleukin-6, and a clustered score of inflammatory biomarkers (InflaScore) (C3,
      C4, CRP, fibrinogen, and leptin). RESULTS: Receiver operating characteristic
      curves analyses showed that C3, C4, CRP, fibrinogen, leptin, and the InflaScore
      were able to present discriminatory ability in identifying an unfavorable
      cardiometabolic profile in both girls and boys (p <.01 for all). Logistic
      regression analyses showed that C3, C4, CRP, fibrinogen, leptin, the InflaScore
      (in both sexes), and WBC (boys) were associated with high cardiometabolic risk,
      independent of age, pubertal stage, socioeconomic status, or adherence to a
      Mediterranean diet (p <.05 for all). CONCLUSIONS: C3, C4, CRP, fibrinogen, and
      leptin were associated with high cardiometabolic risk in both sexes and WBC in
      boys. In addition, the clustered inflammatory biomarkers seem to have a better
      diagnostic accuracy in identifying an unfavorable cardiometabolic profile than
      single biomarkers. Such biomarkers may have utility in motivating health
      professionals, public health workers, and adolescents' families toward lifestyle
      changes, improving prevention efforts early in life.

PMID- 29174877
TI  - Cholinesterase Inhibitor Discontinuation: The Buck Stops Here.

PMID- 29174879
TI  - Spontaneous Cystic Arteriovenous Malformation-A Novel Treatment Alternative.
AB  - BACKGROUND: Brain arteriovenous malformation (BAVM) is a life-threatening
      vascular congenital malformation due to the risk of intracerebral hemorrhage. The
      formation of a spontaneous cyst within a BAVM, without history of hemorrhage or
      gamma knife surgery, is rare and has an unknown pathophysiology. We suggest a
      novel theory of spontaneous cystic BAVM formation, subsequently treated with
      endovascular embolization followed by surgery with a favorable long-term outcome.
      METHODS: Review of the literature using PUBMED database and comparison between
      clinical presentation, diagnostic imaging studies, and treatment options.
      RESULTS: The high flow causing a shear stress over the drainage vein may be
      responsible for venous ectasia and thus incrementing hydrostatic intranidal
      pressure causing a serous effusion that develops into a pseudocyst. We
      hypothesize that hemodynamic factors may be responsible for both origin and
      growth of such cystic lesions. CONCLUSIONS: Endovascular treatment allowed us to
      achieve cyst volume reduction by managing its unique flow characteristics. To our
      knowledge, this is the first case report of combined treatment with endovascular
      and surgical approach of a cystic BAVM.

PMID- 29174878
TI  - Utility of Fractional Anisotropy in Cerebral Peduncle for Stroke Outcome
      Prediction: Comparison of Hemorrhagic and Ischemic Strokes.
AB  - BACKGROUND: Diffusion-tensor fractional anisotropy (FA) has been used for
      predicting stroke outcome. However, most previous studies focused on patients
      with either hemorrhagic or ischemic stroke. The aim of this study was to assess
      the correlation between FA and outcome for patients with hemorrhagic stroke and
      those with ischemic stroke, and then compare their correlation patterns. METHODS:
      This study sampled 40 hemorrhagic and 40 ischemic stroke patients from our
      previously published reports. Diffusion-tensor images were obtained on days 14
      21, and FA images were generated, after which the ratio of FA within the cerebral
      peduncles of the affected and unaffected hemispheres (rFA) was calculated.
      Outcome was assessed using Brunnstrom stage (BRS), motor component of the
      functional independence measure (FIM-motor), and total length of hospital stay
      (LOS) at discharge from our affiliated rehabilitation hospital. The data were
      then compared between the hemorrhage and the infarct groups. Correlation analyses
      between rFA and outcome assessments were performed separately for both groups and
      then were compared between the groups. RESULTS: The hemorrhage group exhibited
      significantly more severe BRS, longer LOS, and lower rFA than the infarct group.
      The correlations between rFA and outcome measures were all statistically
      significant for both the hemorrhage and the infarct groups. The correlation
      patterns for BRS and LOS were very similar between the hemorrhage and the infarct
      groups. However, such similarity was not evident for FIM-motor. CONCLUSIONS: FA
      in the cerebral peduncles may be used to predict extremity functions and LOS for
      both types of stroke.

PMID- 29174880
TI  - How to Make Pediatric Trials Better: Transparency and Accountability of Trial
      Registration and Reporting.

PMID- 29174881
TI  - Reprint of "Anti-therapeutic antibodies and their clinical impact in patients
      treated with the TNF antagonist adalimumab".
AB  - Patients treated with the TNF antagonist adalimumab develop anti-therapeutic
      antibodies (ATA), the prevalence of which varies depending on the assay used.
      Most assays are compromised due to the presence of adalimumab in the clinical
      samples. Our objective was to develop an antibody assay, applicable for clinical
      testing, which overcomes the limitation of therapeutic interference and to
      further determine the relationship between ATA development, adalimumab levels and
      disease activity in patients with rheumatoid arthritis (RA), psoriatic arthritis
      (PsA) or ankylosing spondylitis (AS). Use of an electrochemiluminescence platform
      permitted development of fit-for-purpose immunoassays. Serum samples from
      patients, taken prior to and at 12 and 24 weeks of treatment, were
      retrospectively analysed for levels of adalimumab and ATA. Overall, the antibody
      prevalence was 43.6% at 12 weeks and 41% at 24 weeks of treatment. Disruption of
      immune complexes by acid dissociation, a strategy often adopted for this purpose,
      only marginally increased the antibody prevalence to 48.7% and 46% at 12 and 24
      weeks respectively. We found that antibody formation was associated with
      decreasing levels of circulating adalimumab, but no direct effect on disease
      activity was evident as assessed using DAS28 for RA patients and BASDAI for PsA
      and AS patients. However, a negative correlation of free adalimumab trough levels
      with disease activity scores was observed. Data showed that adalimumab levels can
      serve as an indicator of ATA development which can then be confirmed by ATA
      testing. Monitoring of both therapeutic and antibodies should be considered
      during adalimumab therapy to allow clinicians to personalise treatments for
      maximal therapeutic outcomes.

PMID- 29174882
TI  - Optimizing intraoperative imaging during proximal femoral fracture fixation - a
      performance improvement program for surgeons.
AB  - INTRODUCTION: Formal training for surgeons regarding intraoperative imaging is
      lacking. This project investigated the effect of an educational intervention
      focusing on obtaining and assessing a standardized lateral view of the proximal
      femur during intramedullary nailing of a pertrochanteric fracture. MATERIALS AND
      METHODS: Anatomical landmarks of the proximal femur that can be identified using
      intraoperative fluoroscopy and criteria for image quality, i.e. quality of
      projection were defined in a consensus process, followed by the development of
      educational materials and a 7-item checklist. Five surgeons from 5 Trauma Centers
      in 4 countries participated. Each surgeon a) assessed 5 of their own
      retrospective cases and 5 retrospective cases from 4 colleagues from their
      clinic, b) viewed an educational video and poster and re-assessed the same cases,
      and c) assessed the intraoperative images of 5 prospectively collected
      consecutive cases of their own and of colleagues afterwards. RESULTS: The
      percentage of positive ratings for image quality increased from 72% prior to
      educational intervention to 88% after intervention (p<0.001), and number of "not
      assessable" images decreased significantly. Percentage agreement between surgeons
      on the assessments increased from 75% to 87%. The proportion of best possible
      ratings for fracture reduction and implant position increased from 58% to 72% and
      from 49% to 66%, respectively. Percentage agreement between surgeons on
      assessment of reduction and implant position increased. DISCUSSION AND
      CONCLUSIONS: A focused educational intervention can improve surgeons' ability to
      obtain and assess lateral view intraoperative images of the proximal femur and
      can improve the quality of reduction and implant positioning.

PMID- 29174883
TI  - Estimating abortion provision and abortion referrals among United States
      obstetrician-gynecologists in private practice.
AB  - OBJECTIVE: The objective was to examine the provision of abortion by obstetrician
      gynecologists in private practice in the United States (U.S.) and their
      willingness to provide referrals for abortion services. STUDY DESIGN: We
      conducted a cross-sectional national survey of 1961 U.S. obstetrician
      gynecologists to estimate the frequency with which abortions and referrals for
      abortion care were provided in private practice settings. Key measures included
      whether respondents had provided any abortions in 2013 or 2014, type of abortions
      provided and willingness to provide abortion referrals. Facility location by
      region was the only measured correlate of abortion provision. RESULTS: We
      received a total of 988 surveys for a response rate of 65%. Sixty-seven (7%)
      obstetrician-gynecologists reported providing at least one abortion in 2013 or
      2014, though this result ranged from 4% (n=23) to 13% (n=44) of obstetrician
      gynecologists depending on survey response type. Among physicians practicing in
      the Northeast and West, 14% and 10%, respectively (n=24 in each region) were
      abortion providers compared to 4% (n=9) and 3% (n=10) of physicians in the
      Midwest and South, respectively. Twenty-three (42%) providers indicated only
      performing surgical abortions, 14 (25%) indicated only medication abortions, and
      18 (33%) reported providing both. Among respondents who did not provide
      abortions, just over half (n=415, 54%) indicated that they referred patients to a
      facility or practice where they could obtain an abortion, but 271 (35%) said they
      would not provide a referral. CONCLUSIONS: Only a small proportion of all
      obstetrician-gynecologists in private practice settings provide abortions. Among
      nonproviders, a substantial minority do not offer abortion referrals.
      IMPLICATIONS: Particularly in geographic areas with few abortion providers,
      continued efforts are needed to equip medical professionals with information and
      training to make direct referrals.

PMID- 29174884
TI  - Preoperative progressive pneumoperitoneum in obese patients with loss of domain
      hernias.
AB  - BACKGROUND: Repair of hernias with loss of domain in obese patients can lead to
      acute respiratory failure. OBJECTIVES: The objective of this study was to analyze
      preoperative progressive pneumoperitoneum (PPP) in increasing abdominal cavity
      volume and its impact on respiratory function. SETTING: The study was conducted
      at the University Hospital, State University of Londrina, Brazil, which is a
      referral center for the treatment of obesity. The patients were hospitalized for
      the duration of the study. METHODS: Sixteen obese patients were evaluated.
      Computed tomography was used to determine hernia sac volume (HSV) and abdominal
      cavity volume (ACV). Respiratory function was evaluated by measuring vital
      capacity and forced expiratory volume in the first second (FEV-1). All data were
      obtained before PPP, on the day before surgery, and on the second postoperative
      day. PPP was performed daily with insufflation of CO2. RESULTS: The number of
      insufflations was 12. The average of total volume inflated was 5.7 L. The HSV was
      2953 cm3 before PPP and 1935 cm3 after PPP. The average ACV increased from 8898
      to 11,317 cm3 after PPP. The relationship between HSV and ACV was 38.2% before
      and 16.3% after PPP. There was a favorable improvement in respiratory function
      with an increase in vital capacity from 1875 to 2760 mL and an increase in FEV-1
      from 1060 to 1670 mL after PPP. Respiratory function tests after surgery showed
      values of 2600 and 1560 mL, respectively, for cavity volume and FEV-1. There were
      no postoperative respiratory complications. CONCLUSIONS: This technique can be
      used safely in the surgical preparation of obese patients with hernias with loss
      of domain, reducing the relation between HSV and ACV and avoiding pulmonary
      complications.

PMID- 29174885
TI  - Assessing risk factors, presentation, and management of portomesenteric vein
      thrombosis after sleeve gastrectomy: a multicenter case-control study.
AB  - BACKGROUND: Portomesenteric vein thrombosis (PMVT) is a rare complication of
      laparoscopic sleeve gastrectomy. OBJECTIVES: To identify incidence, patient
      factors, diagnosis, and treatment of PMVT after laparoscopic sleeve gastrectomy
      in a large administrative data registry. SETTING: Academic Hospitals and Private
      Practices, United States. METHODS: A retrospective chart review of 5538 sleeve
      gastrectomy patients between January 1, 2008 and September 30, 2016 was performed
      at 5 bariatric centers in the United States. A total of 11 patients were
      identified as developing PMVT, and 3 controls for each patient were selected by
      matching age, sex, preoperative body mass index, and center. RESULTS: After
      adjusting for confounding variables, 2 patient factors significantly impacted the
      risk of PMVT after sleeve gastrectomy including personal history of malignancy
      (odds ratio 62, 95% confidence interval (CI) 1.4-99.9), and type 2 diabetes (odds
      ratio 12.7, 95% CI 1.2-137.3) compared with controls. Mean period from
      laparoscopic sleeve gastrectomy to presentation of PMVT was 19.3 +/- 15.11 days
      (range, 8-62). All patients except 1 complained of abdominal pain as the main
      presenting symptom. Other complaints included nausea and vomiting, no bowel
      movement, decreased appetite, diarrhea, and dehydration, and leukocytosis was
      present in 45.5% of the patients. All diagnoses were made by using computed
      tomography. All initial treatments were anticoagulation, heparin drip being the
      most common method (90.9%). Of patients, 9 (81.8%) required a secondary
      anticoagulation therapy, and 1 (9.1%) patient required a reoperation. CONCLUSION:
      Incidence of PMVT is low after sleeve gastrectomy. A personal history of
      malignancy and type 2 diabetes increase the risk of PMVT. Increasing abdominal
      pain in a context of dehydration is common presenting symptoms with diagnosis
      confirmed by computed tomography. Anticoagulation is the standard treatment.
      There was no mortality associated with the occurrence of PMVT in this cohort.

PMID- 29174886
TI  - A New Lineage of Eukaryotes Illuminates Early Mitochondrial Genome Reduction.
AB  - The origin of eukaryotic cells represents a key transition in cellular evolution
      and is closely tied to outstanding questions about mitochondrial endosymbiosis
      [1, 2]. For example, gene-rich mitochondrial genomes are thought to be indicative
      of an ancient divergence, but this relies on unexamined assumptions about
      endosymbiont-to-host gene transfer [3-5]. Here, we characterize Ancoracysta
      twista, a new predatory flagellate that is not closely related to any known
      lineage in 201-protein phylogenomic trees and has a unique morphology, including
      a novel type of extrusome (ancoracyst). The Ancoracysta mitochondrion has a gene
      rich genome with a coding capacity exceeding that of all other eukaryotes except
      the distantly related jakobids and Diphylleia, and it uniquely possesses
      heterologous, nucleus-, and mitochondrion-encoded cytochrome c maturase systems.
      To comprehensively examine mitochondrial genome reduction, we also assembled
      mitochondrial genomes from picozoans and colponemids and re-annotated existing
      mitochondrial genomes using hidden Markov model gene profiles. This revealed over
      a dozen previously overlooked mitochondrial genes at the level of eukaryotic
      supergroups. Analysis of trends over evolutionary time demonstrates that gene
      transfer to the nucleus was non-linear, that it occurred in waves of exponential
      decrease, and that much of it took place comparatively early, massively
      independently, and with lineage-specific rates. This process has led to
      differential gene retention, suggesting that gene-rich mitochondrial genomes are
      not a product of their early divergence. Parallel transfer of mitochondrial genes
      and their functional replacement by new nuclear factors are important in models
      for the origin of eukaryotes, especially as major gaps in our knowledge of
      eukaryotic diversity at the deepest level remain unfilled.

PMID- 29174887
TI  - Fbxl4 Serves as a Clock Output Molecule that Regulates Sleep through Promotion of
      Rhythmic Degradation of the GABAA Receptor.
AB  - The timing of sleep is tightly governed by the circadian clock, which contains a
      negative transcriptional feedback loop and synchronizes the physiology and
      behavior of most animals to daily environmental oscillations. However, how the
      circadian clock determines the timing of sleep is largely unclear. In vertebrates
      and invertebrates, the status of sleep and wakefulness is modulated by the
      electrical activity of pacemaker neurons that are circadian regulated and
      suppressed by inhibitory GABAergic inputs. Here, we showed that Drosophila GABAA
      receptors undergo rhythmic degradation in arousal-promoting large ventral lateral
      neurons (lLNvs) and their expression level in lLNvs displays a daily oscillation.
      We also demonstrated that the E3 ligase Fbxl4 promotes GABAA receptor
      ubiquitination and degradation and revealed that the transcription of fbxl4 in
      lLNvs is CLOCK dependent. Finally, we demonstrated that Fbxl4 regulates the
      timing of sleep through rhythmically reducing GABA sensitivity to modulate the
      excitability of lLNvs. Our study uncovered a critical molecular linkage between
      the circadian clock and the electrical activity of pacemaker neurons and
      demonstrated that CLOCK-dependent Fbxl4 expression rhythmically downregulates
      GABAA receptor level to increase the activity of pacemaker neurons and promote
      wakefulness.

PMID- 29174888
TI  - Trans-endocytosis of Planar Cell Polarity Complexes during Cell Division.
AB  - To coordinate epithelial architecture with proliferation, cell polarity proteins
      undergo extensive remodeling during cell division [1-3]. A dramatic example of
      polarity remodeling occurs in proliferative basal cells of mammalian epidermis
      whereupon cell division, transmembrane planar cell polarity (PCP) proteins are
      removed from the cell surface via bulk endocytosis [4]. PCP proteins form
      intercellular complexes, linked by Celsr1-mediated homophilic adhesion, that
      coordinate polarity non-autonomously between cells [5, 6]. Thus, the mitotic
      reorganization of PCP proteins must alter not only proteins intrinsic to the
      dividing cell but also their interacting partners on neighboring cells. Here, we
      show that intercellular Celsr1 complexes that connect dividing cells with their
      neighbors remain intact during mitotic internalization, resulting in an uptake of
      Celsr1 protein from interphase neighbors. Trans-internalized Celsr1 carries with
      it additional core PCP proteins, including the posteriorly enriched Fz6 and
      anteriorly enriched Vangl2. Cadherin-mediated homophilic adhesion is necessary
      for trans-endocytosis, and adhesive junctional PCP complexes appear to be
      destined for degradation upon internalization. Surprisingly, whereas Fz6 and
      Vangl2 both internalize in trans, Vangl2 proteins intrinsic to the dividing cell
      remain associated with the plasma membrane. Persistent Vangl2 stabilizes Celsr1
      and impedes its internalization, suggesting that dissociation of Vangl2 from
      Celsr1 is a prerequisite for Celsr1 endocytosis. These results demonstrate an
      unexpected transfer of PCP complexes between neighbors and suggest that the
      Vangl2 population that persists at the membrane during cell division could serve
      as an internal cue for establishing PCP in new daughter cells.

PMID- 29174889
TI  - Homing Ants Get Confused When Nest Cues Are Also Route Cues.
AB  - The desert ant Cataglyphis fortis inhabits the salt pans of Tunisia. Individual
      ants leave the nest for foraging trips that can cover distances of more than
      1,500 m [1]. Homing ants use path integration [2, 3], but they also rely on
      visual [4] and olfactory [5] nest-defining cues to locate the nest entrance.
      However, nest cues can become ambiguous when they are ubiquitous in the
      environment. Here we show how ants behave during the nest search when the same
      cues occur at the nest and along the route. Homing ants focused their search
      narrowly around a visual or olfactory cue that in training they had experienced
      only at the nest. However, when ants were trained to the same cue not only at the
      nest but also repeatedly along the foraging route, they later exhibited a less
      focused search around the cue. This uncertainty was eliminated when ants had a
      composite cue at the nest that consisted of two components, one unique to the
      nest and another that also occurred along the route. Here, the ants focused their
      search on that part of the binary blend that was presented only at the nest and
      ignored the other, ubiquitous component. Ants thus not only seem to be able to
      pinpoint their nest by following learned visual and olfactory cues, but also take
      into account which cues uniquely specify the nest and which, due to their
      ubiquity, are less informative and so less reliable. VIDEO ABSTRACT.

PMID- 29174890
TI  - Learning Biases Underlie "Universals" in Avian Vocal Sequencing.
AB  - Biological predispositions in vocal learning have been proposed to underlie
      commonalities in vocal sequences, including for speech and birdsong, but cultural
      propagation could also account for such commonalities [1-4]. Songbirds such as
      the zebra finch learn the sequencing of their acoustic elements ("syllables")
      during development [5-8]. Zebra finches are not constrained to learn a specific
      sequence of syllables, but significant consistencies in the positioning and
      sequencing of syllables have been observed between individuals within populations
      and between populations [8-10]. To reveal biological predispositions in vocal
      sequence learning, we individually tutored juvenile zebra finches with randomized
      and unbiased sequences of syllables and analyzed the extent to which birds
      produced common sequences. In support of biological predispositions, birds
      tutored with randomized sequences produced songs with striking similarities.
      Birds preferentially started and ended their song sequence with particular
      syllables, consistently positioned shorter and higher frequency syllables in the
      middle of their song, and sequenced their syllables such that pitch alternated
      across adjacent syllables. These patterns are reminiscent of those observed in
      normally tutored birds, suggesting that birds "creolize" aberrant sequence inputs
      to produce normal sequence outputs. Similar patterns were also observed for
      syllables that were not used for tutoring (i.e., unlearned syllables), suggesting
      that motor biases could contribute to sequence learning biases. Furthermore,
      zebra finches spontaneously produced acoustic patterns that are commonly observed
      in speech and music, suggesting that sensorimotor processes that are shared
      across a wide range of vertebrates could underlie these patterns in humans.

PMID- 29174891
TI  - Local Signals in Mouse Horizontal Cell Dendrites.
AB  - The mouse retina contains a single type of horizontal cell, a GABAergic
      interneuron that samples from all cone photoreceptors within reach and modulates
      their glutamatergic output via parallel feedback mechanisms. Because horizontal
      cells form an electrically coupled network, they have been implicated in global
      signal processing, such as large-scale contrast enhancement. Recently, it has
      been proposed that horizontal cells can also act locally at the level of
      individual cone photoreceptors. To test this possibility physiologically, we used
      two-photon microscopy to record light stimulus-evoked Ca2+ signals in cone axon
      terminals and horizontal cell dendrites as well as glutamate release in the outer
      plexiform layer. By selectively stimulating the two mouse cone opsins with green
      and UV light, we assessed whether signals from individual cones remain isolated
      within horizontal cell dendritic tips or whether they spread across the dendritic
      arbor. Consistent with the mouse's opsin expression gradient, we found that the
      Ca2+ signals recorded from dendrites of dorsal horizontal cells were dominated by
      M-opsin and those of ventral horizontal cells by S-opsin activation. The signals
      measured in neighboring horizontal cell dendritic tips varied markedly in their
      chromatic preference, arguing against global processing. Rather, our experimental
      data and results from biophysically realistic modeling support the idea that
      horizontal cells can process cone input locally, extending the classical view of
      horizontal cell function. Pharmacologically removing horizontal cells from the
      circuitry reduced the sensitivity of the cone signal to low frequencies,
      suggesting that local horizontal cell feedback shapes the temporal properties of
      cone output.

PMID- 29174892
TI  - Stall in Canonical Autophagy-Lysosome Pathways Prompts Nucleophagy-Based Nuclear
      Breakdown in Neurodegeneration.
AB  - The terminal stages of neuronal degeneration and death in neurodegenerative
      diseases remain elusive. Autophagy is an essential catabolic process frequently
      failing in neurodegeneration. Selective autophagy routes have recently emerged,
      including nucleophagy, defined as degradation of nuclear components by autophagy.
      Here, we show that, in a mouse model for the polyglutamine disease dentatorubral
      pallidoluysian atrophy (DRPLA), progressive acquirement of an ataxic phenotype is
      linked to severe cerebellar cellular pathology, characterized by nuclear
      degeneration through nucleophagy-based LaminB1 degradation and excretion. We find
      that canonical autophagy is stalled in DRPLA mice and in human fibroblasts from
      patients of DRPLA. This is evidenced by accumulation of p62 and downregulation of
      LC3-I/II conversion as well as reduced Tfeb expression. Chronic autophagy
      blockage in several conditions, including DRPLA and Vici syndrome, an early-onset
      autolysosomal pathology, leads to the activation of alternative clearance
      pathways including Golgi membrane-associated and nucleophagy-based LaminB1
      degradation and excretion. The combination of these alternative pathways and
      canonical autophagy blockade, results in dramatic nuclear pathology with
      disruption of the nuclear organization, bringing about terminal cell atrophy and
      degeneration. Thus, our findings identify a novel progressive mechanism for the
      terminal phases of neuronal cell degeneration and death in human
      neurodegenerative diseases and provide a link between autophagy block, activation
      of alternative pathways for degradation, and excretion of cellular components.

PMID- 29174893
TI  - The Stone Age Plague and Its Persistence in Eurasia.
AB  - Yersinia pestis, the etiologic agent of plague, is a bacterium associated with
      wild rodents and their fleas. Historically it was responsible for three
      pandemics: the Plague of Justinian in the 6th century AD, which persisted until
      the 8th century [1]; the renowned Black Death of the 14th century [2, 3], with
      recurrent outbreaks until the 18th century [4]; and the most recent 19th century
      pandemic, in which Y. pestis spread worldwide [5] and became endemic in several
      regions [6]. The discovery of molecular signatures of Y. pestis in prehistoric
      Eurasian individuals and two genomes from Southern Siberia suggest that Y. pestis
      caused some form of disease in humans prior to the first historically documented
      pandemic [7]. Here, we present six new European Y. pestis genomes spanning the
      Late Neolithic to the Bronze Age (LNBA; 4,800 to 3,700 calibrated years before
      present). This time period is characterized by major transformative cultural and
      social changes that led to cross-European networks of contact and exchange [8,
      9]. We show that all known LNBA strains form a single putatively extinct clade in
      the Y. pestis phylogeny. Interpreting our data within the context of recent
      ancient human genomic evidence that suggests an increase in human mobility during
      the LNBA, we propose a possible scenario for the early spread of Y. pestis: the
      pathogen may have entered Europe from Central Eurasia following an expansion of
      people from the steppe, persisted within Europe until the mid-Bronze Age, and
      moved back toward Central Eurasia in parallel with human populations.

PMID- 29174894
TI  - Disruption of Perceptual Learning by a Brief Practice Break.
AB  - Some forms of associative learning require only a single experience to create a
      lasting memory [1, 2]. In contrast, perceptual learning often requires extensive
      practice within a day for performance to improve across days [3, 4]. This
      suggests that the requisite practice for durable perceptual learning is
      integrated throughout each day. If the total amount of daily practice is the only
      important variable, then a practice break within a day should not disrupt across
      day improvement. To test this idea, we trained human listeners on an auditory
      frequency-discrimination task over multiple days and compared the performance of
      those who engaged in a single continuous practice session each day [4] with those
      who were given a 30-min break halfway through each practice session. Continuous
      practice yielded significant perceptual learning [4]. In contrast, practice with
      a rest break led to no improvement, indicating that the integration process had
      decayed within 30 min. In a separate experiment, a 30-min practice break also
      disrupted durable learning on a non-native phonetic classification task. These
      results suggest that practice trials are integrated up to a learning threshold
      within a transient memory store before they are sent en masse into a memory that
      lasts across days. Thus, the oft cited benefits of distributed over massed
      training [5, 6] may arise from different mechanisms depending on whether the
      breaks occur before or after a learning threshold has been reached. Trial
      integration could serve as an early gatekeeper to plasticity, helping to ensure
      that longer-lasting changes are only made when deemed worthwhile.

PMID- 29174896
TI  - Kinetic and thermodynamic analysis of dilute acid hydrolysis of sugarcane
      bagasse.
AB  - This study has investigated kinetic and thermodynamic features of dilute acid (2%
      v/v H2SO4, 1:30 w/v) hydrolysis of sugarcane bagasse. Time profiles of xylose
      formation in range of 100 degrees -130  degrees C and treatment period of 0-120
      min have been analysed with modified biphasic Saeman model. Generation of
      glucose, arabinose and inhibitory products (furfural, 5-HMF and acetic acid) have
      also been analysed. Easy-to-hydrolyse fraction of hemicellulose increased with
      temperature. Activation energies for hydrolysis and xylose degradation were 60.3
      and 83.4 kJ/mol, respectively. Although maximum xylose yield (0.81 g/g
      hemicellulose) was obtained at 130  degrees C, significant fraction of xylose was
      converted to inhibitory products. Thermodynamic analysis revealed DeltaH = 57.06
      kJ/mol and DeltaS = -1.05 kJ/mol for hydrolysis. Moreover, xylose formation is
      thermodynamically more favoured (DeltaG = 468.53 kJ/mol) than degradation (DeltaG
      = 482.17 kJ/mol). Optimum conditions for hydrolysis are: temperature = 120 
      degrees C, time = 30 min, xylose yield = 0.76 g/g hemicellulose.

PMID- 29174895
TI  - A Peptide Signaling System that Rapidly Enforces Paternity in the Aedes aegypti
      Mosquito.
AB  - Female Aedes aegypti mosquitoes typically mate only once with one male in their
      lifetime, a behavior known as "monandry" [1]. This single mating event provisions
      the female with sufficient sperm to fertilize the >500 eggs she will produce
      during her ~4- to 6-week lifespan in the laboratory [2]. Successful mating
      induces lifetime refractoriness to subsequent insemination by other males,
      enforcing the paternity of the first male [3-5]. Ae. aegypti mate in flight near
      human hosts [6], and females become refractory to remating within seconds [1, 3,
      4], suggesting the existence of a rapid mechanism to prevent female remating. In
      this study, we implicate HP-I, an Aedes- and male-specific peptide transferred to
      females [7], and its cognate receptor in the female, NPYLR1 [8], in rapid
      enforcement of paternity. HP-I mutant males were ineffective in enforcing
      paternity when a second male was given access to the female within 1 hr. NPYLR1
      mutant females produced mixed paternity offspring at high frequency, indicating
      acceptance of multiple mates. Synthetic HP-I injected into wild-type, but not
      NPYLR1 mutant, virgins reduced successful matings. Asian tiger mosquito (Ae.
      albopictus) HP-I peptides potently activated Ae. aegypti NPYLR1. Invasive Ae.
      albopictus males are known to copulate with and effectively sterilize Ae. aegypti
      females by causing them to reject future mates [9]. Cross-species transfer of
      sperm and active seminal fluid proteins including HP-I may contribute to this
      phenomenon. This signaling system promotes rapid paternity enforcement within Ae.
      aegypti but may promote local extinction in areas where they compete with Ae.
      albopictus.

PMID- 29174897
TI  - Improving the methane yield of maize straw: Focus on the effects of pretreatment
      with fungi and their secreted enzymes combined with sodium hydroxide.
AB  - In order to improve the methane yield, the alkaline and biological pretreatments
      on anaerobic digestion (AD) were investigated. Three treatments were tested:
      NaOH, biological (enzyme and fungi), and combined NaOH with biological. The
      maximum reducing sugar concentrations were obtained using Enzyme T (2.20 mg/mL)
      on the 6th day. The methane yield of NaOH + Enzyme A was 300.85 mL/g TS, 20.24%
      higher than the control. Methane yield obtained from Enzyme (T + A) and Enzyme T
      pretreatments were 277.03 and 273.75 mL/g TS, respectively, which were as
      effective as 1% NaOH (276.16 mL/g TS) in boosting methane production, and are
      environmentally friendly and inexpensive biological substitutes. Fungal
      pretreatment inhibited methane fermentation of maize straw, 15.68% was reduced by
      T + A compared with the control. The simultaneous reduction of DM, cellulose and
      hemicellulose achieved high methane yields. This study provides important
      guidance for the application of enzymes to AD from lignocellulosic agricultural
      waste.

PMID- 29174898
TI  - Effect of aeration interval on oxygen consumption and GHG emission during pig
      manure composting.
AB  - To verify the optimal aeration interval for oxygen supply and consumption and
      investigate the effect of aeration interval on GHG emission, reactor-scale
      composting was conducted with different aeration intervals (0, 10, 30 and 50
      min). Although O2 was sufficiently supplied during aeration period, it could be
      consumed to <10 vol% only when the aeration interval was 50 min, indicating that
      an aeration interval more than 50 min would be inadvisable. Compared to
      continuous aeration, reductions of the total CH4 and N2O emissions as well as the
      total GHG emission equivalent by 22.26-61.36%, 8.24-49.80% and 12.36-53.20%,
      respectively, was achieved through intermittent aeration. Specifically, both the
      total CH4 and N2O emissions as well as the total GHG emission equivalent were
      inversely proportional to the duration of aeration interval (R2 > 0.902),
      suggesting that lengthening the duration of aeration interval to some extent
      could effectively reduce GHG emission.

PMID- 29174899
TI  - The potential of tailoring the conditions of steam explosion to produce xylo
      oligosaccharides from sugarcane bagasse.
AB  - In this study, the potential of the steam explosion (SE) method to produce high
      levels XOS from sugarcane bagasse, a xylan-rich hemicellulosic feedstock, was
      assessed. The effect of different operating conditions on XOS production yield
      and selectivity were investigated using a mini-pilot scale SE unit. The results
      show that even under a non-optimized condition (190  degrees C, 5 min and 0.5%
      H2SO4 as catalyst), SE led to about 40% xylan recovery as XOS, which was
      comparable to the well-known, multi-step, enzymatic production of XOS from
      alkaline-extracted xylan, and other commonly employed chemical methods. In
      addition, the XOS-rich hydrolysate from SE constituted of greater diversity in
      the degree of polymerization, which has been shown to be desirable for prebiotic
      application.

PMID- 29174900
TI  - Co-combustion of sewage sludge and coffee grounds under increased O2/CO2
      atmospheres: Thermodynamic characteristics, kinetics and artificial neural
      network modeling.
AB  - (Co-)combustion characteristics of sewage sludge (SS), coffee grounds (CG) and
      their blends were quantified under increased O2/CO2 atmosphere (21, 30, 40 and
      60%) using a thermogravimetric analysis. Observed percentages of CG mass loss and
      its maximum were higher than those of SS. Under the same atmospheric O2
      concentration, both higher ignition and lower burnout temperatures occurred with
      the increased CG content. Results showed that ignition temperature and
      comprehensive combustion index for the blend of 60%SS-40%CG increased, whereas
      burnout temperature and co-combustion time decreased with the increased O2
      concentration. Artificial neural network was applied to predict mass loss percent
      as a function of gas mixing ratio, heating rate, and temperature, with a good
      agreement between the experimental and ANN-predicted values. Activation energy in
      response to the increased O2 concentration was found to increase from 218.91 to
      347.32 kJ.mol-1 and from 218.34 to 340.08 kJ.mol-1 according to the Kissinger
      Akahira-Sunose and Flynn-Wall-Ozawa methods, respectively.

PMID- 29174901
TI  - Characterization of diversified Sb(V)-reducing bacterial communities by various
      organic or inorganic electron donors.
AB  - This study aims to enrich Sb(V)-reducing bacterial communities from Sb
      contaminated soils using various electron donors for bioremediation of Sb
      contaminated sites and recovery of Sb from wastewater. When the organic electron
      donors were used, Sb(V) reduction rates were 2-24 times faster but electron
      recoveries were 24-59% lower compared to the culture using inorganic electron
      donor. The morphological crystallizations of the antimony-reduced precipitates
      were completely different depending on the electron donor. Different microbial
      populations were enriched with various electron donors but most commonly, only
      Proteobacteria and Firmicutes phyla were enriched from a diversified soil
      microbial community. Geobacter sp. seemed to be an important bacterium in organic
      electron donors-fed cultures whereas an unclassified Rhodocyclaceae was dominant
      in inorganic electron donor-fed cultures. The results indicated that organic
      electron donors especially sugar groups were preferable options to obtain rapid
      Sb(V)-reduction whereas inorganic electron donor like H2 was better option to
      achieve high electron recovery.

PMID- 29174902
TI  - Antibiotic degradation and microbial community structures during acidification
      and methanogenesis of swine manure containing chlortetracycline or
      oxytetracycline.
AB  - Anaerobic digestion (AD) has been applied to animal manure stabilization, and
      antibiotics is frequently found in animal manure. However, antibiotic degradation
      and microbial community structures during two-stage AD (acidification and
      methanogenesis) remain poorly understood. This experiments on two-stage anaerobic
      swine manure digesters were performed to investigate the degradation mechanisms
      and effects of chlortetracycline (CTC) and oxytetracycline (OTC) on microbial
      community structures. Results showed that acidification and methanogenesis showed
      good degradation performance for manure containing CTC and OTC at 60 and 40
      mg/kg.TS, respectively. CTC and OTC were degraded by 59.8% and 41.3% in the
      acidogenic stage and by 76.3% and 78.3% in the methanogenic stage, respectively.
      CTC and OTC negatively affected bacterial community in methanogenic and
      acidogenic stages, respectively. They also adversely influenced the archaeal
      species in the methanogenic stage. Two-stage AD was proposed to treat manure
      containing antibiotics and to reduce the negative effects of antibiotics on AD.

PMID- 29174903
TI  - Boosting bioethanol production from Eucalyptus wood by whey incorporation.
AB  - The mixture of Eucalyptus globulus wood (EGW) and cheese whey powder (CWP) was
      proposed for intensification of simultaneous saccharification and fermentation
      (SSF) at high temperature and solid loadings using the industrial Saccharomyces
      cerevisiae Ethanol Red(r) strain. High ethanol concentration (93 g/L),
      corresponding to 94% ethanol yield, was obtained at 35  degrees C from 37% of
      solid mixture using cellulase and beta-galactosidase enzymes (24.2 FPU/g and 20.0
      U/g, respectively). The use of CWP mixed with pretreated EGW increased the
      ethanol concentration in 1.5-fold, in comparison with SSF experiments without CWP
      for both Ethanol Red(r) and CEN.PK113-7D strains. Moreover, 1.4-fold higher
      ethanol concentration was obtained with Ethanol Red(r), in comparison with
      CEN.PK113-7D strain. Ethanol Red(r) strain was genetically engineered for beta
      galactosidase production in order to advance towards a fully integrated process.
      This work shows the feasibility of attaining high ethanol concentrations in
      second generation bioprocesses by a multi-waste valorization approach.

PMID- 29174904
TI  - Enhanced effects of maghemite nanoparticles on the flocculent sludge wasted from
      a high-rate anammox reactor: Performance, microbial community and sludge
      characteristics.
AB  - Magnetic nanoparticles (NPs) have been widely applied in environmental
      remediation, biomass immobilization and wastewater treatment, but their potential
      impact on anaerobic ammonium oxidation (anammox) biomass remains unknown. In this
      study, the short-term and long-term impacts of maghemite NPs (MHNPs) on the
      flocculent sludge wasted from a high-rate anammox reactor were investigated.
      Batch assays showed that the presence of MHNPs up to 200 mg L-1 did not affect
      anammox activity, reactive oxygen species production, or cell membrane integrity.
      Moreover, long-term addition of 1-200 mg L-1 MHNPs had no adverse effects on
      reactor performance. Notably, the specific anammox activity, the abundance of
      hydrazine synthase structural genes and the content of extracellular polymeric
      substance were increased with elevated MHNP concentrations. Meanwhile, the
      community structure was shifted to higher abundance of Candidatus Kuenenia
      indicated by high-throughput sequencing. Therefore, MHNPs could be applied to
      enhance anammox flocculent sludge due to their favorable biocompatibility.

PMID- 29174905
TI  - Enzymatic hydrolysis of cactus pear varieties with high solids loading for
      bioethanol production.
AB  - The optimization of enzymatic hydrolysis, with high solids loading, of two
      species of cactus pear for bioethanol production was tested evaluating the
      influence of surfactant Tween 80 and pretreatment with H2O and H2SO4 (1% v/v) (50
      degrees C, 150 rpm, 3 h). XRD and FTIR analyzes were performed. Afterwards, the
      influence of the factors cellulase (FPU g-1), pectinase (U g-1) and solids load
      (% w/v), on the hydrolysis of varieties (50  degrees C, 150 rpm, 48 h), and the
      fermentation of the optimal point (33  degrees C, 8 h) were evaluated. The
      pretreatments and the Tween 80 did not increase the hydrolysis yields and
      Rotacional Central Compound Design indicated that the pectinase factor was not
      significant. The best cellulase and solids load conditions were 10 FPU g-1 of
      biomass and 30% w/v for both species. The fermentation efficiency of hydrolysates
      for Nopalea cochenillifera and Opuntia ficus-indica were 76.3% and 82.8%,
      respectively, showing their potential for bioethanol production.

PMID- 29174906
TI  - Novel anaerobic membrane bioreactor (AnMBR) design for wastewater treatment at
      long HRT and high solid concentration.
AB  - Performance of two novel designed anaerobic membrane bioreactor (AnMBRs) for
      wastewater treatment at long hydraulic retention time (HRT, 47 days) and high
      sludge concentration (22 g.L-1) was investigated. Results showed steady chemical
      oxygen demand (COD) removal (>98%) and mean biogas generation of 0.29 LCH4.g
      1COD. Average permeates flux of 58.70 L.m-2.h-1 and 54.00 L.m-2.h-1 were achieved
      for reactors A and B, respectively. On top of reactor configuration, long HRT
      caused biofilm reduction by heterotrophic bacteria Chloroflexi resulting in high
      membrane flux. Mean total membrane resistances (2.23 * 109 m-1) and fouling rates
      (4.00 * 108 m-1.day-1) of both reactors were low suggesting better membrane
      fouling control ability of both AnMBRs. Effluent quality analysis showed the
      effluent soluble microbial products (SMP) were dominated by proteins compared to
      carbohydrates, and specific ultraviolet absorbance (SUVA) analysis revealed
      effluent from both reactors had low aromaticity with SUVA < 1 (L.mg-1.m-1) except
      for the first ten days.

PMID- 29174907
TI  - The influence of complex fermentation broth on denitrification of saline sewage
      in constructed wetlands by heterotrophic nitrifying/aerobic denitrifying
      bacterial communities.
AB  - An experimental vertical-flow constructed wetland (CW) was tested to treat salt
      containing sewage. CW clogging deposits and withered Pontederia cordata L. were
      collected into a complex fermentation broth to serve as the carbon source and its
      effects on the denitrification capacity and microbial composition of the CW were
      examined. Addition of the complex fermentation broth into the CW influent (1.8%
      salinity) led to high removal efficiencies of NH4+-N > 99.82 +/- 0.00% and TN >
      90.39 +/- 0.05%. Heterotrophic nitrifiers and aerobic denitrifiers were entirely
      dominant in the middle and upper layers of the CW, where obligate halophilic,
      aerobic denitrifiers Zobellella occurred. The CW successfully cultivated and
      enriched heterotrophic nitrifying-aerobic denitrifying bacteria, overcoming the
      effects of salinity and insufficient organic carbon sources on the
      denitrification capacity of CW. This type of complex carbon sources can also
      facilitate the utilization of waste resources, such as CW clogging deposits and
      withered wetland plants.

PMID- 29174908
TI  - Integrated bioethanol production to boost low-concentrated cellulosic ethanol
      without sacrificing ethanol yield.
AB  - Four integrated designs were proposed to boost cellulosic ethanol titer and
      yield. Results indicated co-fermentation of corn flour with hydrolysate liquor
      from saccharified corn stover was the best integration scheme and able to boost
      ethanol titers from 19.9 to 123.2 g/L with biomass loading of 8% and from 36.8 to
      130.2 g/L with biomass loadings of 16%, respectively, while meeting the minimal
      ethanol distillation requirement of 40 g/L and achieving high ethanol yields of
      above 90%. These results indicated integration of first and second generation
      ethanol production could significantly accelerate the commercialization of
      cellulosic biofuel production. Co-fermentation of starchy substrate with
      hydrolysate liquor from saccharified biomass is able to significantly enhance
      ethanol concentration to reduce energy cost for distillation without sacrificing
      ethanol yields. This novel method could be extended to any pretreatment of
      biomass from low to high pH pretreatment as demonstrated in this study.

PMID- 29174909
TI  - Integration process of fermentation and liquid biphasic flotation for lipase
      separation from Burkholderia cepacia.
AB  - Liquid Biphasic Flotation (LBF) is an advanced recovery method that has been
      effectively applied for biomolecules extraction. The objective of this
      investigation is to incorporate the fermentation and extraction process of lipase
      from Burkholderia cepacia using flotation system. Initial study was conducted to
      compare the performance of bacteria growth and lipase production using flotation
      and shaker system. From the results obtained, bacteria shows quicker growth and
      high lipase yield via flotation system. Integration process for lipase separation
      was investigated and the result showed high efficiency reaching 92.29% and yield
      of 95.73%. Upscaling of the flotation system exhibited consistent result with the
      lab-scale which are 89.53% efficiency and 93.82% yield. The combination of
      upstream and downstream processes in a single system enables the acceleration of
      product formation, improves the product yield and facilitates downstream
      processing. This integration system demonstrated its potential for biomolecules
      fermentation and separation that possibly open new opportunities for industrial
      production.

PMID- 29174910
TI  - Corrigendum to "Enhanced expression of caveolin-1 possesses diagnostic and
      prognostic value and promotes cell migration, invasion and sunitinib resistance
      in the clear cell renal cell carcinoma" [Exp. Cell Res. (2017) 269-278].

PMID- 29174911
TI  - Modulation of Corticospinal Excitability of Trunk Muscles in Preparation of Rapid
      Arm Movement.
AB  - Many studies have described the dynamic modulation of corticospinal excitability
      of the prime movers during motor preparation. However although anticipatory
      postural adjustments (APA) are an inherent part of most voluntary movements,
      investigation of trunk muscle corticospinal excitability during motor preparation
      has been neglected in the literature. In the present study, the corticospinal
      excitability of the superficial multifidus (sMF) and rectus abdominis (RA) muscle
      has been assessed during the preparation of rapid arm flexions and extensions in
      fifteen participants. A Warning signal informed participants to prepare to move
      prior to a Go signal. Transcranial magnetic stimulation was applied during
      baseline and at 6 time intervals before (Delay period) or after (Motor execution
      period) the Go signal. Results revealed a significant inhibition of the amplitude
      of sMF motor-evoked potentials in both flexion and extension movements within the
      Delay period compared to baseline, while no significant modulation was observed
      for RA. During the Motor Execution period for arm extension, sMF displayed even
      more inhibition, along with a large and significant facilitation of RA. During
      the Motor execution period for arm flexion, sMF presented a trend toward larger
      motor-evoked potential amplitude compared to Delay period. These results suggest
      the existence of two concurrent mechanisms underlying motor preparation for APA:
      (i) before the Go signal, a nonspecific inhibitory mechanism for sMF, likely to
      preclude motor program release; (ii) after the Go signal, a task-specific
      modulation of corticospinal excitability consistent with the EMG pattern during
      the early phase of movement.

PMID- 29174912
TI  - Behavioral responses and fluid regulation in male rats after combined dietary
      sodium deficiency and water deprivation.
AB  - Most investigators use a single treatment such as water deprivation or dietary
      sodium deficiency to evaluate thirst or sodium appetite, which underlie
      behavioral responses to body fluid challenges. The goal of the present
      experiments was to assess the effects of combined treatments in driving
      behaviors. Therefore, we evaluated the effect of combined overnight water
      deprivation and dietary sodium deficiency on water intake and salt intake by
      adult male rats in 2-bottle (0.5M NaCl and water) tests. Overnight water
      deprivation alone increased water intake, and 10days of dietary sodium deficiency
      increased 0.5M NaCl intake, with a secondary increase in water intake. During
      combined water deprivation and dietary sodium deficiency, water intake was
      enhanced and 0.5M NaCl was reduced, but not eliminated, suggesting that
      physiologically relevant behavioral responses persist. Nonetheless, the pattern
      of fluid intake was altered by the combined treatments. We also assessed the
      effect of these behaviors on induced deficits in body sodium and fluid volume
      during combined treatments and found that, regardless of treatment, fluid
      ingestion partially repleted the induced deficits. Finally, we examined urine
      volume and sodium excretion during dietary sodium deficiency with or without
      overnight water deprivation and found that, whether or not rats were water
      deprived, and regardless of water consumption, sodium excretion was minimal.
      Thus, the combination of water deprivation and dietary sodium deficiency appears
      to arouse drives that stimulate compensatory behavioral responses. These
      behaviors, in conjunction with physiological adaptations to the treatments,
      underlie body sodium and volume repletion in the face of combined water
      deprivation and dietary sodium deficiency.

PMID- 29174913
TI  - Effects of cordycepin on spontaneous alternation behavior and adenosine receptors
      expression in hippocampus.
AB  - Cordycepin, an adenosine analogue, has been reported to improve cognitive
      function. Important roles on learning and memory of adenosine and its receptors,
      such as adenosine A1 and A2A receptors (A1R and A2AR), also have been shown.
      Therefore, we assume that the improvement of learning and memory induced by
      cordycepin is likely related to hippocampal adenosine content and adenosine
      receptor density. Here we investigated the effects of cordycepin on the short
      term spatial memory by using a spontaneous alternation behavior (SAB) test in Y
      maze, and then examined hippocampal adenosine content and A1R and A2AR densities.
      We found that orally administrated cordycepin (at dosages of 5 and 10mg/kg twice
      daily for three weeks) significantly increased the percent of relative
      alternation of mice in SAB but not altered body weight, hippocampus weight and
      hippocampal adenosine content. Furthermore, cordycepin decreased A2AR density in
      hippocampal subareas; however, cordycepin only reduced the A1R density in DG but
      not CA1 or CA3 region. Our results suggest that cordycepin exerts a nootropic
      role possibly through modulating A2AR density of hippocampus, which further
      support the concept that it is mostly A2AR rather than A1R to control the
      adaptive processes of memory performance. These findings would be helpful to
      provide a new window into the pharmacological properties of cordycepin for
      cognitive promotion.

PMID- 29174914
TI  - Src family kinases (SFKs) and cell polarity in the testis.
AB  - Non-receptor Src family kinases (SFKs), most notably c-Src and c-Yes, are
      recently shown to be expressed by Sertoli and/or germ cells in adult rat testes.
      Studies have shown that SFKs are involved in modulating the cell cytoskeletal
      function, and involved in endocytic vesicle-mediated protein endocytosis,
      transcytosis and/or recycling as well as intracellular protein degradation
      events. Furthermore, a knockdown to SFKs, in particular c-Yes, has shown to
      induce defects in spermatid polarity. These findings, coupled with emerging
      evidence in the field, thus prompt us to critically evaluate them to put forth a
      developing concept regarding the role of SFKs and cell polarity, which will
      become a basis to design experiments for future investigations.

PMID- 29174916
TI  - Guidance of retinal axons in mammals.
AB  - In order to navigate through the surrounding environment many mammals, including
      humans, primarily rely on vision. The eye, composed of the choroid, sclera,
      retinal pigmented epithelium, cornea, lens, iris and retina, is the structure
      that receives the light and converts it into electrical impulses. The retina
      contains six major types of neurons involving in receiving and modifying visual
      information and passing it onto higher visual processing centres in the brain.
      Visual information is relayed to the brain via the axons of retinal ganglion
      cells (RGCs), a projection known as the optic pathway. The proper formation of
      this pathway during development is essential for normal vision in the adult
      individual. Along this pathway there are several points where visual axons face
      'choices' in their direction of growth. Understanding how these choices are made
      has advanced significantly our knowledge of axon guidance mechanisms. Thus, the
      development of the visual pathway has served as an extremely useful model to
      reveal general principles of axon pathfinding throughout the nervous system.
      However, due to its particularities, some cellular and molecular mechanisms are
      specific for the visual circuit. Here we review both general and specific
      mechanisms involved in the guidance of mammalian RGC axons when they are
      traveling from the retina to the brain to establish precise and stereotyped
      connections that will sustain vision.

PMID- 29174917
TI  - Non-identical twins: Different faces of CR3 and CR4 in myeloid and lymphoid cells
      of mice and men.
AB  - Integrins are cell membrane receptors that are involved in essential
      physiological and serious pathological processes. Their main role is to ensure a
      closely regulated link between the extracellular matrix and the intracellular
      cytoskeletal network enabling cells to react to environmental stimuli. Complement
      receptor type 3 (CR3, alphaMbeta2, CD11b/CD18) and type 4 (CR4, alphaXbeta2,
      CD11c/CD18) are members of the beta2-integrin family expressed on most white
      blood cells. Both receptors bind multiple ligands like iC3b, ICAM, fibrinogen or
      LPS. beta2-integrins are accepted to play important roles in cellular adhesion,
      migration, phagocytosis, ECM rearrangement and inflammation. Several pathological
      conditions are linked to the impaired functions of these receptors. CR3 and CR4
      are generally thought to mediate overlapping functions in monocytes, macrophages
      and dendritic cells, therefore the potential distinctive role of these receptors
      has not been investigated so far in satisfactory details. Lately it has become
      clear that a functional segregation has evolved between the two receptors
      regarding phagocytosis, cellular adhesion and podosome formation. In addition to
      their tasks on myeloid cells, the expression and function of CR3 and CR4 on
      lymphocytes have also gained interest recently. The picture is further
      complicated by the fact that while these beta2-integrins are expressed by immune
      cells both in mice and humans, there are significant differences in their
      expression level, functions and the pathological consequences of genetic defects.
      Here we aim to summarize our current knowledge on CR3 and CR4 and highlight the
      functional differences between these receptors, involving their expression in
      myeloid and lymphoid cells of both men and mice.

PMID- 29174915
TI  - Midline axon guidance in the Drosophila embryonic central nervous system.
AB  - Studies in the fruit fly Drosophila melanogaster have provided many fundamental
      insights into the genetic regulation of neural development, including the
      identification and characterization of evolutionarily conserved axon guidance
      pathways and their roles in important guidance decisions. Due to its highly
      organized and fast-developing embryonic nervous system, relatively small number
      of neurons, and molecular and genetic tools for identifying, labeling, and
      manipulating individual neurons or small neuronal subsets, studies of axon
      guidance in the Drosophila embryonic CNS have allowed researchers to dissect
      these genetic mechanisms with a high degree of precision. In this review, we
      discuss the major axon guidance pathways that regulate midline crossing of axons
      and the formation and guidance of longitudinal axon tracts, two processes that
      contribute to the development of the precise three-dimensional structure of the
      insect nerve cord. We focus particularly on recent insights into the roles and
      regulation of canonical midline axon guidance pathways, and on additional factors
      and pathways that have recently been shown to contribute to axon guidance
      decisions at and near the midline.

PMID- 29174918
TI  - Response: Nitroblue tetrazolium (NBT) assay.

PMID- 29174920
TI  - Editorial overview: Inequality and social class: The psychological and behavioral
      consequences of inequality and social class: a theoretical integration.

PMID- 29174919
TI  - Chemotherapy for alpha-fetoprotein producing gastric cancers expressing human
      epidermal growth factor receptor 2.
AB  - Although, gastric cancer is one of the most common cancers worldwide, alpha
      fetoprotein (AFP) producing human epidermal growth factor receptor 2 (HER2)
      positive gastric cancers are rare. AFP producing gastric cancer has a poor
      prognosis and an appropriate treatment option has not been established to date. A
      75-year-old woman with AFP- producing gastric cancer was treated with S-1, an
      oral fluoropyrimidine derivative, chemotherapy after distal gastrectomy.
      Recurrence of gastric cancer was observed after 18 months and
      immunohistochemistry analysis showed AFP and HER2 positive gastric cancer. The
      patient received combination therapy containing capecitabine, cisplatin, and
      trastuzumab. Computed tomography scans showed regression of the lymph node
      metastasis. The patient's quality of life substantially improved after the
      treatment. Thus, the present case suggests that AFP and HER2 positive gastric
      cancer can be effectively treated with, capecitabine, cisplatin, and trastuzumab
      combination therapy.

PMID- 29174921
TI  - Embryonic development of GABAergic terminals in the mouse hypothalamic nuclei
      involved in feeding behavior.
AB  - The inhibitory neurotransmitter gamma-amino butyric acid (GABA) plays important
      roles in energy balance and feeding behavior in the hypothalamus. To reveal the
      time course of GABAergic network formation, we examined the immunohistochemical
      localization of glutamic acid decarboxylase (GAD), a GABAergic neuron marker,
      vesicular GABA transporter (VGAT), a marker of inhibitory terminals, and K+-Cl-
      cotransporter2 (KCC2), which shifts GABA action from excitation to inhibition, in
      the developing mouse hypothalamus. GABAergic terminals, seen as GAD- and VGAT
      positive dots, increased in density during embryonic development. Moreover, the
      onset of KCC2 localization was almost concomitant with GABAergic terminal
      formation, and KCC2-positive profiles increased in density during development.
      This suggested that after the formation of GABAergic terminals, GABAergic action
      may change to inhibition in the hypothalamus. This maturation appears to proceed
      as follows: the lateral hypothalamus (LH) matures first, followed by the
      paraventricular nucleus (PVN) by the time of birth, while the ventromedial
      hypothalamus (VMH) and the arcuate nucleus (Arc) are not fully mature at the time
      of birth. Our findings suggest that GABAergic networks in the "feeding center"
      (LH) and the "exit" (PVN) may mature before birth, while those in the "satiety
      center" (VMH) and "higher control center" (Arc) may mature after birth.

PMID- 29174922
TI  - Detecting spinal pyramidal tract of amyotrophic lateral sclerosis patients with
      diffusion tensor tractography.
AB  - The objective of this study was to determine alteration of corticospinal tract in
      patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor
      tractograhy (DTT) focusing on the cervical spinal cord (C5) and transcranial
      magnetic stimulation (TMS). We recruited 38 ALS, 6 spinal and bulbar muscular
      atrophy (SBMA), 7 spastic paraplegia (SP) patients, and 8 age-matched normal
      controls, and then ALS were divided into two subgroups according to their
      clinical type: 28 ALS-limb and 10 ALS-bulbar. DTT was performed using the
      diffusion tensor image (DTI) track module to reconstruct two fiber tracts via C5.
      The fractional anisotropy (FA) values of ALS-total and ALS-limb patients were
      significantly reduced compared with normal controls, and SBMA patients. On the
      other hand, the mean diffusivity (MD) values were not significantly different
      among normal controls and the three disease groups. The rate of disease
      progression (DeltaFRS-R) of ALS patients was significantly correlated with FA
      values and central motor conduction time (CMCT). In conclusion, the present study
      demonstrated a significant reduction of FA values in ALS patients, and the
      DeltaFRS-R of ALS patients showed distinct regressions with FA values and CMCT,
      suggesting that this DTT analysis could be useful for detecting disease
      progression of ALS patients.

PMID- 29174923
TI  - Inorganic nitrite and nitrate in cardiovascular therapy: A better alternative to
      organic nitrates as nitric oxide donors?
AB  - In 1867 the organic nitrite, amyl nitrite, was introduced as a therapeutic agent
      in the treatment of angina pectoris and was later substituted by the organic
      nitrate nitroglycerin (NTG). Despite having a highly potent vasodilator capacity
      in veins>coronary arteries>arterioles, the vasodilator effects NTG are rapidly
      attenuated by the development of nitrate tolerance. We and others established
      that NTG treatment stimulates the production of reactive oxygen species such as
      superoxide and peroxynitrite with subsequent marked attenuation of the NTG
      vasodilator potency. The nitrite anion (NO2-) has more recently been
      characterized to possess novel pharmacotherapeutic actions such as modulation of
      vasodilation under hypoxic conditions, thereby providing protection in ischemia
      reperfusion injury. Administration of NO2-/NO3- has also been shown to improve
      myocardial function in heart failure and to lower blood pressure. Despite these
      positive aspects there is still a great need to study inorganic nitrate and
      nitrite therapy in various cardiovascular diseases in prospective outcome
      directed studies. In case being successful, this kind of therapy would indeed
      represent a cheap, therefore affordable, effective cardiovascular therapy without
      major side effects as observed in response to therapy with organic nitrates.

PMID- 29174925
TI  - The administration of surfactant decreased oxidative stress in lungs of mice
      exposed to cigarette smoke.
AB  - The alveolar surfactant, which composition consists of a unique and complex
      mixture of lipids and proteins, has immunomodulatory action. This study aimed to
      evaluate the effects of exogenous surfactant on pulmonary inflammatory response
      in mice exposed to cigarette smoke (CS). Twenty-four mice C57BL/6 were divided
      into four groups: control group exposed to ambient air (CG); surfactant treated
      group (SG); CS exposed group (CSG) and CS exposed group treated with surfactant
      (CSSG). For five days, CSG and CSSG were exposed to 12 commercial cigarettes/day
      and SG and CSSG received the surfactant by intranasal instillation. At the end of
      the experiment, the animals were euthanatized for the collection of
      bronchoalveolar lavage fluid (BALF) and lungs. The total number of leukocytes in
      BALF increased in CSG compared to CG, however, there was a decrease in CSSG
      compared to CSG. There was an increase in lipid peroxidation in SG and CSG
      compared to CG while there was a decrease in CSSG compared to CSG. Regarding the
      antioxidant enzymes, the catalase (CAT) activity increased in all groups compared
      to CG and the superoxide dismutase (SOD) activity decreased in CSG compared to
      the CG and SG. There was an increase in TNF in SG, CSG and CSSG compared to CG.
      There was an increase in IL-17 in CSSG compared to CG. There was an increase in
      CCL5 in SG and CSSG compared to CG. Therefore, our results demonstrated that the
      administration of exogenous surfactant was able to decrease the oxidative
      processes in the lungs of mice induced by short-term exposure to CS.

PMID- 29174924
TI  - The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA
      Processing Machinery Is Limiting.
AB  - Many eukaryotic genes generate linear mRNAs and circular RNAs, but it is largely
      unknown how the ratio of linear to circular RNA is controlled or modulated. Using
      RNAi screening in Drosophila cells, we identify many core spliceosome and
      transcription termination factors that control the RNA outputs of reporter and
      endogenous genes. When spliceosome components were depleted or inhibited
      pharmacologically, the steady-state levels of circular RNAs increased while
      expression of their associated linear mRNAs concomitantly decreased. Upon
      inhibiting RNA polymerase II termination via depletion of the
      cleavage/polyadenylation machinery, circular RNA levels were similarly increased.
      This is because readthrough transcripts now extend into downstream genes and are
      subjected to backsplicing. In total, these results demonstrate that inhibition or
      slowing of canonical pre-mRNA processing events shifts the steady-state output of
      protein-coding genes toward circular RNAs. This is in part because nascent RNAs
      become directed into alternative pathways that lead to circular RNA production.

PMID- 29174926
TI  - Factors Associated With Response to Teduglutide in Patients With Short-Bowel
      Syndrome and Intestinal Failure.
AB  - BACKGROUND & AIMS: Clinical studies showed teduglutide to increase urine
      production and reduce need for parenteral support volume in patients with short
      bowel syndrome (SBS) with intestinal failure, increasing intestinal wet weight
      absorption and reducing diarrhea. However, the effects of teduglutide on
      parenteral support vary among patients. We performed a post hoc analysis of a
      phase III placebo-controlled study to identify characteristics of patients in
      whom teduglutide has the largest effects on parenteral support volume response.
      METHODS: We collected data from 85 patients with SBS with intestinal failure,
      according to the European Society for Clinical Nutrition and Metabolism
      classification system, who received teduglutide or placebo between November 25,
      2008, and January 4, 2011, at 27 sites in 10 countries. Changes in parenteral
      support volume were evaluated according to baseline parenteral support volume,
      bowel anatomy (group 1, jejunostomy/ileostomy; group 2, >=50% colon-in-continuity
      without stoma; and group 3, other colon anatomies), and disease features (with
      inflammatory bowel disease, mesenteric vascular diseases, or other conditions).
      Correlation analyses were conducted using simple linear regression models, with
      unadjusted r2 values reported. Two-sided t tests were used for comparisons
      between treatment groups. RESULTS: We correlated parenteral support volume
      reduction with teduglutide treatment and baseline parenteral support volume (y = 
      0.3870x + 90.0279, r2 = 0.61; P < .0001). The effects of teduglutide on absolute
      parenteral support volume were significantly greater in group 1 patients
      (reduction of 919 +/- 644 mL/d), not only compared with patients given placebo
      (reduction of 340 +/- 436 mL/d; P = .0112) but also compared with teduglutide
      treated patients in group 2 (reduction of 355 +/- 306 mL/d; P = .0066).
      Teduglutide had an intermediate effect on patients in group 3. A minority of
      patients with SBS and inflammatory bowel diseases had colon-in-continuity (10.5%
      [n = 2/19]), whereas most patients with SBS and vascular or other diseases had
      colon-in-continuity (84.4% [n = 27/32] and 67.6% [n = 23/34], respectively).
      CONCLUSIONS: In a post hoc analysis of data from a phase III study of the effects
      of teduglutide on patients with SBS, we associated reduced parenteral support
      volume with baseline parenteral support volume, bowel anatomy, and SBS features.
      These findings may inform initial parenteral support volume adjustments and
      management of these severely disabled patients. ClinicalTrials.gov no:
      NCT00798967; ClinicalTrialsRegister.eu no: 2008-006193-15.

PMID- 29174927
TI  - Computed Tomography Colonography vs Colonoscopy for Colorectal Cancer
      Surveillance After Surgery.
AB  - BACKGROUND & AIMS: Recommendations for surveillance after curative surgery for
      colorectal cancer (CRC) include a 1-year post-resection abdominal-pelvic computed
      tomography (CT) scan and optical colonoscopy (OC). CT colonography (CTC), when
      used in CRC screening, effectively identifies colorectal polyps >=10 mm and
      cancers. We performed a prospective study to determine whether CTC, concurrent
      with CT, could substitute for OC in CRC surveillance. METHODS: Our study enrolled
      231 patients with resected stage 0-III CRC, identified at 5 tertiary care
      academic centers. Approximately 1 year after surgery, participants underwent
      outpatient CTC plus CT, followed by same-day OC. CTC results were revealed after
      endoscopic visualization of sequential colonic segments, which were re-examined
      for discordant findings. The primary outcome was performance of CTC in the
      detection of colorectal adenomas and cancers using endoscopy as the reference
      standard. RESULTS: Of the 231 participants, 116 (50.2%) had polyps of any size or
      histology identified by OC, and 15.6% had conventional adenomas and/or serrated
      polyps >=6 mm. No intra-luminal cancers were detected. CTC detected patients with
      polyps of >=6 mm with 44.0% sensitivity (95% CI, 30.2-57.8) and 93.4% specificity
      (95% CI, 89.7-97.0). CTC detected polyps >=10 mm with 76.9% sensitivity (95% CI,
      54.0-99.8) and 89.0% specificity (95% CI, 84.8-93.1). Similar values were found
      when only adenomatous polyps were considered. The negative predictive value of
      CTC for adenomas >=6 mm was 90.7% (95% CI, 86.7-94.5) and for adenomas >=10 mm
      the negative predictive value was 98.6% (95% CI, 97.0-100). CONCLUSIONS: In a CRC
      surveillance population 1 year following resection, CTC was inferior to OC for
      detecting patients with polyps >=6 mm. Clinical Trials.gov Registration Number:
      NCT02143115.

PMID- 29174929
TI  - Erratum to "Trans sectoral care of geriatric cancer patients based on
      comprehensive geriatric assessment and patient-reported quality of life - Results
      of a multicenter study to develop and pilot test a patient-centered
      interdisciplinary care concept for geriatric oncology patients (PIVOG)" [J
      Geriatr Oncol 8 (2017) 262-270].

PMID- 29174930
TI  - The use of fine needle aspiration and trends in incidence of thyroid cancer in
      Taiwan.
AB  - BACKGROUND: Thyroid cancer is the most prevalent endocrine malignancy, and the
      incidence of thyroid cancer has increased worldwide. Fine needle aspiration (FNA)
      for cytology of thyroid tissue is used for differentiating thyroid cancers from
      benign thyroid nodules. Overuse of FNA may detect subclinical thyroid cancer and
      play a role in the increased incidence of thyroid cancer. The aim of this study
      was to evaluate trends in incidence of thyroid cancer and the use of palpation
      guided FNA thyroid and ultrasound-guided FNA thyroid in Taiwan. METHODS: By
      retrospectively analyzing a cohort dataset of one million people randomly sample
      to represent as NHI beneficiaries of Taiwan National Health Insurance Research
      Database from 2004 to 2010, patients who received palpation-guided and ultrasound
      guided thyroid FNA were identified. Individuals who were diagnosed as having
      thyroid cancer were determined. Age-standardized, yearly rates of palpation
      guided thyroid FNA and ultrasound-guided FNA, and age-standardized, yearly
      incidence rates of thyroid cancer were calculated. RESULTS: In the study period,
      a total of 541 patients were newly diagnosed with thyroid cancer, 14,240
      individuals received palpation-guided thyroid FNA, and 3823 individuals underwent
      ultrasound-guided thyroid FNA. There was a 94.8% increase in the age-standardized
      annual incidence rate of thyroid cancer. The age-standardized rates of palpation
      guided thyroid FNA and ultrasound-guided thyroid FNA increased by 10.9% and
      349.3%, respectively. CONCLUSION: FNA for cytology of thyroid tissue, especially
      ultrasound-guided FNA, was conducted by physicians more frequently in Taiwan.
      Increased use of FNA, especially ultrasound-guided FNA for cytology of thyroid
      tissue, may attribute to the increased incidence of thyroid cancer in Taiwan.

PMID- 29174931
TI  - Group 1. Epidemiology of primary and secondary adrenal insufficiency: Prevalence
      and incidence, acute adrenal insufficiency, long-term morbidity and mortality.
AB  - The prevalence of primary adrenal insufficiency is estimated at between 82
      144/million, with auto-immunity being the most common cause in adults and genetic
      causes, especially enzyme defects, being the most common cause in children. The
      prevalence of secondary adrenal deficiency is estimated to be between 150
      280/million. The most frequent occurrence is believed to be corticosteroid
      induced insufficiency, despite the incidence of clinically relevant deficiency
      after cessation of glucocorticoid treatment being widely debated. Data on
      mortality in adrenal insufficiency are contradictory, with studies from Sweden
      suggesting a two-fold increase in comparison to the general population, but this
      is not consistently reported in all studies. However, increased mortality has
      been consistently reported in young patients, associated with infection and/or
      acute adrenal insufficiency. Acute adrenal deficiency (adrenal crisis) occurs in
      primary as well as secondary adrenal insufficiency. Its incidence, mostly
      determined in retrospective studies, is estimated in Europe at 6-8/100
      patients/year. A prospective study reported 0.5 deaths/100 patient-years from
      adrenal crisis. Long-term morbidity of adrenal insufficiency is not well
      established, the increased cardiovascular risk or bone demineralization which are
      not consistently reported may also be due to a supraphysiological glucocorticoid
      replacement therapy. However, alteration in quality of life, both in physical and
      mental health components, has been demonstrated by several studies in both
      primary and secondary adrenal insufficiency.

PMID- 29174928
TI  - Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of
      Patients With Ulcerative Colitis.
AB  - BACKGROUND & AIMS: Indigo naturalis (IN) is a traditional Chinese medicine that
      contains ligands for the aryl hydrocarbon receptor and promotes regeneration of
      the mucosa by inducing production of interleukin 22. IN might induce mucosal
      healing in patients with ulcerative colitis (UC). We performed a randomized
      controlled trial to investigate the safety and efficacy of IN in patients with
      UC. METHODS: We performed a multicenter, double-blind trial evaluating the safety
      of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from
      March 30 through December 27, 2016. Patients were randomly assigned to groups and
      given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8
      weeks. The primary endpoint was the rate of clinical response at week 8, defined
      as a 3-point decrease in the Mayo score and a decrease of at least 30% from
      baseline, with a decrease of at least 1 point for the rectal bleeding subscore or
      absolute rectal bleeding score of 0-1. The main secondary endpoint was the rate
      of clinical remission at week 8, defined as a Mayo score or <=2 and no subscores
      with a value >1. Mucosal healing was also assessed at week 8. RESULTS: The trial
      was terminated because of an external reason: a report of pulmonary arterial
      hypertension in a patient who used self-purchased IN for 6 months. In the intent
      to-treat analysis, we observed a significant, dose-dependent linear trend in
      proportions of patients with clinical responses (13.6% with a clinical response
      to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran
      Armitage trend test P < .0001 compared with placebo). Proportions of patients in
      clinical remission at week 8 were significantly higher in the 1.0 g IN group
      (55.0%, P = .0004) and the 2.0 g IN group (38.1%, (P = .0093) than in the placebo
      group (4.5%). Proportions of patients with mucosal healing were 13.6% in the
      placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and
      47.6% in the 2.0 g IN group (P = .0278 compared with placebo). Although mild
      liver dysfunction was observed in 10 patients who received IN, no serious adverse
      events were observed. CONCLUSIONS: In a randomized, placebo-controlled trial, we
      found 8 weeks of IN (0.5-2.0 g per day) to be effective in inducing a clinical
      response in patients with UC. However, IN should not yet be used because of the
      potential for adverse effects, including pulmonary arterial hypertension.
      Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).

PMID- 29174932
TI  - Group 3: Strategies for identifying the cause of adrenal insufficiency:
      diagnostic algorithms.

PMID- 29174933
TI  - Surviving at a distant site: The organotropism of metastatic breast cancer.
AB  - Many cancers demonstrate a non-random distribution of sites for distant relapse
      while others have the propensity to metastasize to multiple organ systems. One of
      the notable recent findings is that the breast cancer subtypes differ not only in
      their biological characteristics as primary tumors but also in their capacity for
      metastatic progression. This information could potentially be utilized in
      treatment decision making and surveillance strategies.

PMID- 29174934
TI  - Primary lesions that may imitate metastatic tumors histologically: A selective
      review.
AB  - Several primary pathologic entities in diverse anatomic locations have the
      potential to simulate metastatic neoplasms histologically. Their
      misinterpretation as such may result in needless and extensive clinical
      evaluations that are intended to detect a presumed malignancy at another site.
      More importantly, mistakes of this type can deprive patients of surgical
      excisions that could be curative. This presentation considers a review of
      selected primary lesions that can simulate metastases. They include
      hemangioblastoma, glioblastoma and meningioma with epithelial metaplasia, choroid
      plexus carcinomas, primary neuroendocrine carcinomas in unusual locations,
      special forms of sinonasal and salivary glandular adenocarcinoma, clear-cell
      thyroid carcinomas, unusual microscopic subtypes of pulmonary adenocarcinoma,
      epithelioid myomelanocytomas ("sugar tumors"), mesotheliomas, primary thymic
      carcinomas, endodermal choristomas of the interatrial myocardium, peripheral
      cholangiocarcinoma, adrenocortical carcinoma, adenocarcinomas of the urinary
      bladder, mucinous and "rhabdoid" tumors of the ovaries, rete testis
      adenocarcinomas, interdigitating dendritic-cell sarcoma of lymph nodes, selected
      sweat gland carcinomas, cutaneous Merkel cell carcinoma, primary dermal and
      subcutaneous melanoma, mucosal and visceral melanomas, epithelioid sarcoma, clear
      cell sarcoma, and adamantinoma of long bones. Differential diagnostic
      observations are emphasized in reference to those lesions.

PMID- 29174935
TI  - The impact of adjuvant vaginal brachytherapy in women with Stage II uterine
      endometrioid carcinoma: Results of a National Cancer Database analysis.
AB  - PURPOSE: To report survival outcomes in women with Stage II uterine endometrioid
      carcinoma who received adjuvant radiation therapy (RT) without chemotherapy using
      the National Cancer Database. METHODS AND MATERIALS: The National Cancer Database
      was queried for women with International Federation of Gynecology and Obstetrics
      Stage II uterine endometrioid carcinoma who underwent hysterectomy followed by
      adjuvant RT without chemotherapy. The chi2 tests were performed to compare
      differences in outcome by type of adjuvant RT (external beam radiation therapy
      [EBRT] alone, vaginal brachytherapy [VBT] alone, or combination of EBRT and VBT).
      Overall survival (OS) was assessed by Kaplan-Meier and log-rank tests. Univariate
      and multivariate analyses were performed to identify predictors of OS. RESULTS:
      We identified 2681 women. Simple hysterectomy was performed on 2261 women (84%).
      Adjuvant EBRT, VBT, and combination RT were administered to 27%, 36%, and 37%,
      respectively. There was a statistically significant difference in OS by modality
      of adjuvant RT (p = 0.01) favoring women who received VBT alone or in combination
      with EBRT. The 5-year OS was 80%, 87%, and 83% for women who received EBRT, VBT,
      and combination RT, respectively (p = 0.001). On multivariate analysis, old age,
      African-American race, no or fewer number of examined lymph nodes, and higher
      tumor grade were independent predictors of worse OS. RT modality did not sustain
      its independent prognostic significance as a predictor of OS. CONCLUSIONS: In
      this nationwide hospital-based study of women with International Federation of
      Gynecology and Obstetrics Stage II uterine endometrioid carcinoma, adjuvant VBT
      alone provided excellent survival outcomes and may be a reasonable adjuvant RT
      modality for properly selected women with adequate lymph node dissection and low
      grade tumors.

PMID- 29174936
TI  - Quantitative CT assessment of a novel direction-modulated brachytherapy tandem
      applicator.
AB  - PURPOSE: The purpose of this study was to quantitatively assess the CT metal
      induced artifacts from a novel direction-modulated brachytherapy (DMBT) tandem
      applicator prototype, recently designed for cervical cancer treatments. METHODS
      AND MATERIALS: A water-based pelvic phantom was constructed for CT scanning. The
      DMBT applicator was imaged using our institutional protocol, one with higher kVp
      and mAs settings, and repetition of these protocols using 3-mm slices. A
      conventional stainless steel applicator was also scanned. In addition to the
      standard reconstructed images, applicator images were reconstructed using a
      commercial metal artifact-reduction (MAR) algorithm and an in-house-developed
      research algorithm. Subsequently, image quality and artifact severity were
      evaluated. RESULTS: Artifact severity, measured in terms of SDs in CT numbers,
      decreased asymptotically to background water levels with the distance away from
      the applicator. Artifact-reduction algorithms lead to significant and visible
      improvements in image quality, with >50% and >20% decrease in artifact severity
      achieved at a 10-mm distance for the DMBT and stainless steel applicators,
      respectively. Differences in artifact severity were minimal between the four
      imaging protocols. DMBT dimensions were the same on images with and without the
      commercial MAR algorithm, within <1 mm of the theoretical value. Both the
      commercial and in-house algorithms restored the CT numbers outside the
      applicator, albeit a better performance was achieved by the in-house algorithm.
      CONCLUSIONS: The artifacts produced by both applicators were minimized with the
      use of MAR algorithms. Adoption of the DMBT and stainless steel applicators for
      CT-guided brachytherapy is anticipated as MAR algorithms are widely available on
      CT scanners.

PMID- 29174938
TI  - Plesiobrachytherapy for chest wall recurrences of breast cancer after mastectomy
      and radiotherapy for breast cancer.
AB  - PURPOSE: The purpose of the study was to evaluate the results of high-dose-rate
      plesiobrachytherapy for local relapse after mastectomy and radiotherapy in terms
      of both local control and survival. METHODS: We reviewed retrospectively 43
      patients who experienced a chest wall relapse of breast cancer after local
      excision (22 patients) or not (21 patients). Patients were treated with an
      individually designed mold with four to six fractions of 3-6 Gy high-dose-rate
      brachytherapy, two fractions per week. Mean total dose was 24 Gy. RESULTS: After
      surgical resection, the 3- and 5-year local control rates were 80% and 73%,
      respectively. For nonresectable patients, the overall response rate was 86%, and
      the 3-year infield local control and chest wall local control were 51% and 26%,
      respectively. The 5-year survival rate was 50.5% for the whole population, 62%
      after surgery, and 45.4% for irresectable patients. Acute Grade 2 or 3 toxicity
      occurred in 43% of the patients, resolving in a few days. Two patients had a
      local necrosis lasting 3 to 7 months. Late toxicity was observed in 5 patients.
      CONCLUSIONS: High-dose-rate plesiobrachytherapy is a simple outpatient technique
      to treat chest wall local relapse of breast cancer. As a reirradiation technique,
      its tolerance is acceptable. This technique may obtain long-term local control
      after incomplete surgery; in case of nonresectable disease, a high response rate
      was observed, which might improve the quality of life of these patients.

PMID- 29174937
TI  - Reductions in prostatic doses are associated with less acute morbidity in
      patients undergoing Pd-103 brachytherapy: Substantiation of the rationale for
      focal therapy.
AB  - PURPOSE: Interest in prostate dose reduction or focal treatment exists due to
      expected reductions in treatment morbidity. Prior analyses have not generally
      corroborated relationships between prostate or urethral dose and urinary toxicity
      after brachytherapy, but such analyses have been performed on cohorts all
      receiving the same prescribed dose. We analyzed patients treated to differing
      prescription doses to assess acute urinary morbidity with dose reduction. METHODS
      AND MATERIALS: Patients treated with Pd-103 to either 125 Gy or 90-100 Gy were
      compared using the International Prostate Symptom Score (IPSS) at 1-month
      postimplant. Patients in the 90-100 Gy cohort began external beam radiation
      therapy after their 1-month assessment; thus, toxicities were measured before
      contribution from external beam radiation therapy. Patient/treatment
      characteristics were compared to verify subgroup homogeneity. Dose and change in
      IPSS 1 month after treatment were assessed using a multivariate linear regression
      model. RESULTS: One hundred ninety-one and 41 patients were treated with 125 Gy
      versus 90-100 Gy, respectively. Preimplant and postimplant prostate volumes and
      initial IPSS were similar between groups. Higher prescription dose and increased
      pretreatment IPSS were independent predictors of increased 1-month IPSS. In
      addition, every 10 percentage point additional prostate volume receiving a given
      dose was associated with increase in IPSS after treatment for the same level of
      pretreatment IPSS. CONCLUSION: Lower prescription dose and decreased volume of
      high-dose regions to the prostate correlated with reduced acute urinary morbidity
      after brachytherapy. Our findings suggest that focal treatment approaches with
      modest dose reductions to subregions of the prostate may reduce acute morbidity
      and potentially expand the number of patients eligible for brachytherapy.

PMID- 29174939
TI  - Physician Intervention to Positive Depression Screens Among Adolescents in
      Primary Care.
AB  - PURPOSE: The objective of this study was to determine the effectiveness of
      computer-based screening and physician feedback to guide adolescent depression
      management within primary care. METHODS: We conducted a prospective cohort study
      within two clinics of the computer-based depression screening and physician
      feedback algorithm among youth aged 12-20 years between October 2014 and October
      2015 in Marion County (Indianapolis), Indiana. RESULTS: Our sample included 2,038
      youth (51% female; 60% black; mean age = 14.6 years [standard deviation = 2.1]).
      Over 20% of youth screened positive for depression on the Patient Health
      Questionnaire-2 and 303 youth (14.8%) screened positive on the Patient Health
      Questionnaire-9 (PHQ-9). The most common follow-up action by physicians was a
      referral to mental health services (34.2% mild, 46.8% moderate, and 72.2% severe
      range). Almost 11% of youth in the moderate range and 22.7% of youth in the
      severe range were already prescribed a selective serotonin reuptake inhibitor.
      When predicting mental health service referral, significant predictors in the
      multivariate analysis included clinic site (40.2% vs. 73.9%; p < .0001) and PHQ-9
      score (severe range 77.8% vs. mild range 47.5%; p < .01). Similarly, when
      predicting initiation of selective serotonin reuptake inhibitors, only clinic
      site (28.6% vs. 6.9%; p < .01) and PHQ-9 score (severe range 46.7% vs. moderate
      range 10.6%; p < .001) were significant. CONCLUSIONS: When a computer-based
      decision support system algorithm focused on adolescent depression was
      implemented in two primary care clinics, a majority of physicians utilized
      screening results to guide clinical care.

PMID- 29174940
TI  - Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review
      of Phase 3 Clinical Trial Published Data.
AB  - OBJECTIVE: To provide an update on SpaceOAR System, a Food and Drug
      Administration-approved hydrogel indicated to create distance between the
      prostate and the rectum which has been studied in phase 2 and 3 clinical trials.
      Here, we review and summarize these clinical results including the safety of
      prostate-rectum spacer application technique, the implant quality and resulting
      rectal dose reduction, acute and long-term rectal, urinary, and sexual toxicity,
      as well as patient-reported outcomes. MATERIALS AND METHODS: A prospective,
      randomized patient-blinded clinical study was performed comparing image-guided
      intensity modulated prostate radiotherapy (79.2 Gy in 44 fractions) in men with
      or without prostate-rectum hydrogel spacer. Patients were followed up for 3
      years, allowing assessment of long-term safety and efficacy. RESULTS: Spacer
      application was well tolerated with a 99% technical success rate. The mean
      additional space created between the prostate and the rectum was just over 1 cm,
      which allowed significant rectum and penile bulb radiation dose reduction,
      resulting in less acute pain, lower rates of late rectal toxicity, and improved
      bowel and urinary quality of life (QOL) scores from 6 months onward. Improvements
      in sexual QOL were also observed at 37 months in baseline-potent men, with 37.5%
      of control and 66.7% of spacer men capable of "erections sufficient for
      intercourse." CONCLUSION: Prostate-rectum hydrogel spacer application is a
      relatively safe technical procedure that is well tolerated and has a high
      technical success rate. Spacer application significantly reduces rectal radiation
      dose and results in long-term reductions in rectal toxicity, as well as
      improvements in bowel, urinary, and sexual QOL.

PMID- 29174941
TI  - Is Delayed Phase Computed Tomography Imaging Necessary After Blunt Renal Trauma
      in Children?
AB  - OBJECTIVE: To characterize the utilization of delayed phase computed tomography
      (CT) imaging in blunt renal trauma and determine if the omission of delayed phase
      CT imaging affected clinical outcomes in children. MATERIALS AND METHODS: A
      prospectively collected trauma database was reviewed between 2006 and 2016 to
      identify patients aged <=21 years with a diagnosis of renal injury from blunt
      trauma. Demographic characteristics, injury grade, Injury Severity Score, non
      kidney organ injuries, radiologic studies, and clinical course were reviewed.
      Patients were categorized into 2 groups: those who received CT with delayed
      images in the emergency room and those who did not. RESULTS: In total, 121
      patients met the inclusion criteria. Delayed scans were obtained in 50 patients
      (41%) but omitted in 71 (59%). Age, weight, non-kidney organ injuries, and
      imaging location did not differ between groups. Injury Severity Score was higher
      in the no-delay group than in the delay group (median 16 vs 10, respectively, P =
      .40). Median length of stay was 3 days without significant differences by cohort
      (P = .24). The proportion of patients who received abdominal CT scans after
      admission, underwent a urologic procedure, or were readmitted did not differ
      significantly between groups. CONCLUSION: This study was unable to demonstrate a
      difference in outcomes between patients who had a CT with delayed imaging and
      patients who did not. This questions the universal necessity for delayed images
      after blunt renal trauma. Future prospective studies are necessary to develop
      pediatric trauma guidelines that balance imaging needs and radiation exposure.

PMID- 29174942
TI  - Comparative Effectiveness of Initial Surgery vs Initial Systemic Therapy for
      Metastatic Kidney Cancer in the Targeted Therapy Era: Analysis of a Population
      based Cohort.
AB  - OBJECTIVE: To use econometric methods to assess comparative overall survival of
      patients with metastatic renal cell carcinoma (mRCC) managed with initial
      cytoreductive nephrectomy (CN) vs initial systemic therapy. Randomized data
      demonstrate improved survival for CN preceding cytokine-based therapy in mRCC.
      This benefit may be attenuated in the contemporary mRCC era given more effective
      systemic therapies. METHODS: Patients over age 65 with mRCC from the
      Surveillance, Epidemiology, and End Results registries linked with Medicare
      claims from 2006 to 2011 were categorized by initial treatment. We applied
      sequential survival analysis methods to assess the association between initial CN
      and overall survival (OS) including Cox proportional hazards models, propensity
      scoring, and instrumental variable analysis to account for measured and
      unmeasured selection bias. RESULTS: Of 537 patients analyzed, 190 had initial CN
      followed by targeted therapy and 347 had initial targeted therapy. Median OS in
      the initial CN group was 17.4 months (interquartile range 9.8-32.0), compared
      with 9.2 months (interquartile range 4.3-18.0) for initial targeted therapy. Cox
      proportional hazards analysis revealed initial CN was associated with improved OS
      (hazard ratio 0.50, 95% confidence interval [CI] 0.38-0.65). Propensity matching
      demonstrated a survival advantage for initial CN of 5.8 months (95% CI 1.9-9.7).
      Accounting for unmeasured confounding with instrumental variable analysis
      demonstrated a trend toward improved survival with initial CN (hazard ratio 0.29
      [95% CI 0.08-1.00]). CONCLUSION: Initial CN is associated with improved survival
      compared with initial systemic therapy in a contemporary population-based mRCC
      cohort.

PMID- 29174943
TI  - Use of 99mTc-sestamibi Single-photon Emission Computed Tomography / X-ray
      Computed Tomography in the Diagnosis of Hybrid Oncocytic / Chromophobe Tumor in a
      Pediatric Patient.
AB  - The differential diagnosis of solid renal neoplasms in adolescence includes
      aggressive malignancy and indolent oncocytic tumors, which are typically
      indistinguishable using conventional imaging. We report the use of 99mTc
      sestamibi single-photon emission computed tomography / x-ray computed tomography
      (SPECT/CT) in characterizing enhancing renal neoplasms in a pediatric patient.
      Genetic testing suggested a hereditary syndrome associated with aggressive
      malignancy, whereas renal mass biopsy suggested an oncocytic tumor. 99mTc
      sestamibi SPECT/CT indicated probable oncocytomas or hybrid oncocytic /
      chomophobe tumors. Enucleative resection was performed with final pathology
      demonstrating hybrid oncocytic / chomophobe tumors. This case highlights the
      potential utility of 99mTc-sestamibi SPECT/CT in characterizing indeterminate
      enhancing renal neoplasm in pediatric patients.

PMID- 29174944
TI  - Is there a benefit to adjuvant radiation in stage III penile cancer after lymph
      node dissection? Findings from the National Cancer Database.
AB  - OBJECTIVE: The role of adjuvant radiation in advanced penile cancer (PC) is
      unknown. We used the National Cancer Database (NCDB) to determine factors
      associated with receiving adjuvant radiation (aXRT) and their influence on
      prognosis in men who underwent inguinal lymph node dissection (ILND) for stage
      III disease. MATERIALS AND METHODS: We queried the NCDB from 1998-2012 for all
      men with PC who had pathologic nodal status and aXRT data available. Clinical and
      pathologic variables associated with aXRT were examined using chi-square testing.
      Logistic regression evaluated the odds of receiving aXRT while multivariate Cox
      regression analysis evaluated the influence of aXRT on overall survival (OS).
      RESULTS: A total of 589 patients underwent ILND for stage III PC with 23% (N =
      136) receiving aXRT. Mean age was 61.8 +/-13.7 years. Factors associated with
      receiving aXRT included higher pathologic nodal stage (MV OR 1.85, 95% CI: 1.13
      3.05), while greater distance of travel (MV OR 0.48, 95% CI: 0.25-0.92), and
      treatment in an academic setting (MV OR 0.53, 95% CI: 0.35-0.81) were inversely
      associated with receiving aXRT. On Cox regression analysis, aXRT improved OS
      (combined HR 0.58, 95% CI: 0.39-0.86), which appeared to have been driven by
      higher nodal burden (N2: HR 0.53, 95% CI: 0.32-0.88; N1: HR 1.36, 95% CI: 0.60
      3.09). CONCLUSIONS: Determinants of aXRT delivery in stage III PC appear to be
      related to the proximity to community cancer centers and greater nodal burden. We
      find evidence of a survival benefit with the use of aXRT, particularly in those
      with higher nodal stage. Multi-institutional studies are needed to confirm these
      findings and improve treatment algorithms for high-stage PC.

PMID- 29174945
TI  - Preoperative predictors of nonorgan-confined disease in upper-tract urothelial
      carcinoma differ between China and the United States.
AB  - OBJECTIVE: To compare preoperative predictors of nonorgan-confined (NOC) disease
      in patients with upper-tract urothelial carcinoma (UTUC) from the United States
      (US) and China. METHODS: Clinicopathologic data of patients with UTUC treated
      surgically at tertiary care facilities in the US or China from 1998 to 2015 were,
      retrospectively, compiled. Patient characteristics, preoperative imaging,
      cytology, ureteroscopic findings, and serum markers (neutrophil-to-lymphocyte
      ratio, estimated glomerular filtration rate, hemoglobin, and albumin) were
      evaluated. After excluding patients who received neoadjuvant chemotherapy, rates
      of NOC disease at definitive surgery were tabulated. Logistic regression and
      receiver operating characteristic analyses were performed to determine predictors
      of NOC for each country using previously published nomograms, and the cohorts
      were compared. RESULTS: Totally, 753 patients with UTUC were included for
      analysis (451 Chinese and 302 US). NOC rates were similar between the 2 countries
      (31% vs. 29%, P = 0.568). On multivariable analysis, cT3 stage (P = 0.001) and
      high-grade pathology on ureteroscopy (P = 0.011) were significant predictors for
      NOC in the US, while male gender (P = 0.034), tumor location on imaging (P =
      0.009), tumor size on imaging (P = 0.044), neutrophil-to-lymphocyte (P = 0.043),
      and preoperative estimated glomerular filtration rate (P = 0.028) were
      significant in China. Areas under the curve differed by nomogram used (Western
      model: 0.750 in US, vs. 0.670 in China; Chinese model: 0.763 in US, vs. 0.828 in
      China). CONCLUSION: Predictors for NOC in UTUC differ between the US and China.
      There may be unique population-based markers that more profoundly influence the
      accuracy of nomograms in certain populations. Our findings highlight the
      importance of considering population differences when clinically applying
      predictive tools in UTUC.

PMID- 29174946
TI  - Fluoxetine, not donepezil, reverses anhedonia, cognitive dysfunctions and
      hippocampal proteome changes during repeated social defeat exposure.
AB  - While anhedonia is considered a core symptom of major depressive disorder (MDD),
      less attention has been paid to cognitive dysfunctions. We evaluated the
      behavioural and molecular effects of a selective serotonin re-uptake inhibitor
      (SSRI, fluoxetine) and an acetylcholinesterase inhibitor (AChEI, donepezil) on
      emotional-cognitive endophenotypes of depression and the hippocampal proteome. A
      chronic social defeat (SD) procedure was followed up by "reminder" sessions of
      direct and indirect SD. Anhedonia-related behaviour was assessed longitudinally
      by intracranial self-stimulation (ICSS). Cognitive dysfunction was analysed by an
      object recognition test (ORT) and extinction of fear memory. Tandem mass
      spectrometry (MSE) and protein-protein-interaction (PPI) network modelling were
      used to characterise the underlying biological processes of SD and SSRI/AChEI
      treatment. Independent selected reaction monitoring (SRM) was conducted for
      molecular validation. Repeated SD resulted in a stable increase of anhedonia-like
      behaviour as measured by ICSS. Fluoxetine treatment reversed this phenotype,
      whereas donepezil showed no effect. Fluoxetine improved recognition memory and
      inhibitory learning in a stressor-related context, whereas donepezil only
      improved fear extinction. MSE and PPI network analysis highlighted functional SD
      stress-related hippocampal proteome changes including reduced glutamatergic
      neurotransmission and learning processes, which were reversed by fluoxetine, but
      not by donepezil. SRM validation of molecular key players involved in these
      pathways confirmed the hypothesis that fluoxetine acts via increased AMPA
      receptor signalling and Ca2+-mediated neuroplasticity in the amelioration of
      stress-impaired reward processing and memory consolidation. Our study highlights
      molecular mediators of SD stress reversed by SSRI treatment, identifying
      potential viable future targets to improve cognitive dysfunctions in MDD
      patients.

PMID- 29174947
TI  - RBFOX1, encoding a splicing regulator, is a candidate gene for aggressive
      behavior.
AB  - The RBFOX1 gene (or A2BP1) encodes a splicing factor important for neuronal
      development that has been related to autism spectrum disorder and other
      neurodevelopmental phenotypes. Evidence from complementary sources suggests that
      this gene contributes to aggressive behavior. Suggestive associations with RBFOX1
      have been identified in genome-wide association studies (GWAS) of anger, conduct
      disorder, and aggressive behavior. Nominal association signals in RBFOX1 were
      also found in an epigenome-wide association study (EWAS) of aggressive behavior.
      Also, variants in this gene affect temporal lobe volume, a brain area that is
      altered in several aggression-related phenotypes. In animals, this gene has been
      shown to modulate aggressive behavior in Drosophila. RBFOX1 has also been
      associated with canine aggression and is upregulated in mice that show increased
      aggression after frustration of an expected reward. Associated common genetic
      variants as well as rare duplications and deletions affecting RBFOX1 have been
      identified in several psychiatric and neurodevelopmental disorders that are often
      comorbid with aggressive behaviors. In this paper, we comprehensively review the
      cumulative evidence linking RBFOX1 to aggression behavior and provide new results
      implicating RBFOX1 in this phenotype. Most of these studies (genetic and
      epigenetic analyses in humans, neuroimaging genetics, gene expression and animal
      models) are hypothesis-free, which strengthens the validity of the findings,
      although all the evidence is nominal and should therefore be taken with caution.
      Further studies are required to clarify in detail the role of this gene in this
      complex phenotype.

PMID- 29174948
TI  - Divergent prefrontal dopaminergic mechanisms mediate drug- and fear-associated
      cue extinction during adolescence versus adulthood.
AB  - Cue-associated learning is vital to guiding behaviour for survival. Adolescence
      represents a key developmental stage for perturbations in cue-related learning,
      including a characteristic deficit in cue extinction learning. The present review
      summarizes evidence from animal and human literature that cue extinction is
      critically mediated by prefrontal dopamine, a system that undergoes dramatic
      reorganization during adolescence. We propose that extinction learning and memory
      is governed by a developmentally dynamic balance of dopamine receptors in the
      prefrontal cortex, which changes across adolescence into adulthood. This is
      contrary to the previous idea that extinction deficits during adolescence reflect
      inefficiency in the same neural circuitry as adults. This leads to proposal of
      the novel theory that cue extinction involves divergent prefrontal dopaminergic
      mechanisms depending on the age of extinction.

PMID- 29174949
TI  - Impaired repair of DNA damage is associated with autistic-like traits in rats
      prenatally exposed to valproic acid.
AB  - Prenatal exposure to the antiepileptic and mood stabilizer valproic acid (VPA) is
      an environmental risk factor for autism spectrum disorders (ASD), although recent
      epidemiological studies show that the public awareness of this association is
      still limited. Based on the clinical findings, prenatal VPA exposure in rodents
      is a widely used preclinical model of ASD. However, there is limited information
      about the precise biochemical mechanisms underlying the link between ASD and VPA.
      Here, we tested the effects of increasing doses of VPA on behavioral features
      resembling core and secondary symptoms of ASD in rats. Only when administered
      prenatally at the dose of 500mg/kg, VPA induced deficits in communication and
      social discrimination in rat pups, and altered social behavior and emotionality
      in the adolescent and adult offspring in the absence of gross malformations. This
      dose of VPA inhibited histone deacetylase in rat embryos and favored the
      formation of DNA double strand breaks (DSB), but impaired their repair. The
      defective DSB response was no more visible in one-day-old pups, thus supporting
      the hypothesis that unrepaired VPA-induced DNA damage at the time of neural tube
      closure may underlie the autistic-like traits displayed in the course of
      development by rats prenatally exposed to VPA. These experiments help to
      understand the neurodevelopmental trajectories affected by prenatal VPA exposure
      and identify a biochemical link between VPA exposure during gestation and ASD.

PMID- 29174950
TI  - A formative evaluation of a coach-based technical assistance model for youth- and
      family-focused programming.
AB  - BACKGROUND: The Children, Youth, and Families At-Risk (CYFAR) initiative provides
      funding and technical support for local community-based programs designed to
      promote positive outcomes among vulnerable populations. In 2013, CYFAR
      implemented significant changes in the way it provides technical assistance (TA)
      to grantees. These changes included introducing a new TA model in which trained
      coaches provide proactive support that is tailored to individual CYFAR projects.
      The purpose of this paper is to describe the evolution of this TA model and
      present preliminary findings from a formative evaluation. METHODS: CYFAR
      Principal Investigators (PIs) were invited to respond to online surveys in 2015
      and 2016. The surveys were designed to assess PI attitudes towards the nature and
      quality of support that they receive from their coaches. RESULTS: CYFAR PIs
      reported that their coaches have incorporated a range of coaching skills and
      techniques into their work. PIs have generally positive attitudes towards their
      coaches, and these attitudes have become more positive over time. CONCLUSIONS:
      Results suggest that CYFAR PIs have been generally supportive of the new TA
      system. Factors that may have facilitated support include a strong emphasis on
      team-building and the provision of specific resources that support program
      design, implementation, and evaluation.

PMID- 29174951
TI  - Vocational training and employability: Evaluation evidence from Romania.
AB  - This study evaluates the direct effects of vocational training, which is a
      popular active labour market policy in a European developing country such as
      Romania. Since the available official statistical microdata were insufficient to
      conduct reliable impact evaluations, the main findings were obtained through a
      counterfactual impact evaluation using newly produced micro survey data.
      Moreover, the research provides a heterogeneity analysis of groups of trainees,
      in order to identify the categories for which the programme performs best. The
      main results reveal that the training measure has a positive, but modest impact
      upon employability in Romania: participation increases employment chances
      properly controlled by 15%. It is most successful for women and for people living
      in urban areas. Measures for increasing the impacts of the vocational training
      programme in Romania are identified in terms of better targeting and profiling
      the trainees and closer adjustment of the programme to the specific needs of the
      labour market.

PMID- 29174953
TI  - Signature Celebration of Gastroenterology, Colorectal Cancer.

PMID- 29174952
TI  - Interactions Between Diet and the Intestinal Microbiota Alter Intestinal
      Permeability and Colitis Severity in Mice.
AB  - BACKGROUND & AIMS: It is not clear how the complex interactions between diet and
      the intestinal microbiota affect development of mucosal inflammation or
      inflammatory bowel disease. We investigated interactions between dietary
      ingredients, nutrients, and the microbiota in specific pathogen-free (SPF) and
      germ-free (GF) mice given more than 40 unique diets; we quantified individual and
      synergistic effects of dietary macronutrients and the microbiota on intestinal
      health and development of colitis. METHODS: C56BL/6J SPF and GF mice were placed
      on custom diets containing different concentrations and sources of protein, fat,
      digestible carbohydrates, and indigestible carbohydrates (fiber). After 1 week,
      SPF and GF mice were given dextran sulfate sodium (DSS) to induce colitis.
      Disease severity was determined based on the percent weight change from baseline,
      and modeled as a function of the concentration of each macronutrient in the diet.
      In unchallenged mice, we measured intestinal permeability by feeding mice labeled
      dextran and measuring levels in blood. Feces were collected and microbiota were
      analyzed by 16S rDNA sequencing. We collected colons from mice and performed
      transcriptome analyses. RESULTS: Fecal microbiota varied with diet; the
      concentration of protein and fiber had the strongest effect on colitis
      development. Among 9 fiber sources tested, psyllium, pectin, and cellulose fiber
      reduced the severity of colitis in SPF mice, whereas methylcellulose increased
      severity. Increasing dietary protein increased the density of the fecal
      microbiota and the severity of colitis in SPF mice, but not in GF mice or mice
      given antibiotics. Psyllium fiber reduced the severity of colitis through
      microbiota-dependent and microbiota-independent mechanisms. Combinatorial
      perturbations to dietary casein protein and psyllium fiber in parallel accounted
      for most variation in gut microbial density and intestinal permeability in
      unchallenged mice, as well as the severity of DSS-induced colitis; changes in 1
      ingredient could be offset by changes in another. CONCLUSIONS: In an analysis of
      the effects of different dietary components and the gut microbiota on mice with
      and without DSS-induced colitis, we found complex mixtures of nutrients affect
      intestinal permeability, gut microbial density, and development of intestinal
      inflammation.

PMID- 29174954
TI  - Cell milieu significantly affects the fate of AApoAI amyloidogenic variants:
      predestination or serendipity?
AB  - BACKGROUND: Specific apolipoprotein A-I variants are associated to severe
      hereditary amyloidoses. The organ distribution of AApoAI amyloidosis seems to
      depend on the position of the mutation, since mutations in residues from 1 to 75
      are mainly associated to hepatic and renal amyloidosis, while mutations in
      residues from 173 to 178 are mostly responsible for cardiac, laryngeal, and
      cutaneous amyloidosis. Molecular bases of this tissue specificity are still
      poorly understood, but it is increasingly emerging that protein destabilization
      induced by amyloidogenic mutations is neither necessary nor sufficient for
      amyloidosis development. METHODS: By using a multidisciplinary approach,
      including circular dichroism, dynamic light scattering, spectrofluorometric and
      atomic force microscopy analyses, the effect of target cells on the conformation
      and fibrillogenic pathway of the two AApoAI amyloidogenic variants AApoAIL75P and
      AApoAIL174S has been monitored. RESULTS: Our data show that specific cell milieus
      selectively affect conformation, aggregation propensity and fibrillogenesis of
      the two AApoAI amyloidogenic variants. CONCLUSIONS: An intriguing picture emerged
      indicating that defined cell contexts selectively induce fibrillogenesis of
      specific AApoAI variants. GENERAL SIGNIFICANCE: An innovative methodological
      approach, based on the use of whole intact cells to monitor the effects of cell
      context on AApoAI variants fibrillogenic pathway, has been set up.

PMID- 29174955
TI  - Cleft lip and palate subjects prevalence of abnormal stylohyoid complex and
      tonsilloliths on cone beam computed tomography.
AB  - INTRODUCTION AND OBJECTIVES: Tonsilloliths and abnormal stylohyoid complex may
      have similar symptoms to others of different aetiology. Individuals with cleft
      lip and palate describe similar symptoms because of the anatomical implications
      that are peculiar to this anomaly. The aim of this study was to determine the
      prevalence of abnormal stylohyoid complex and tonsilloliths on cone beam computed
      tomography in individuals with cleft lip and palate. METHODS: According to the
      inclusion and exclusion criteria, 66 CT scans out of of 2,794 were analysed, on i
      Cat (r) vision software with 0.8 index Kappa intra-examiner. RESULTS: The total
      prevalence of ossification of the incomplete stylohyoid complex in individuals
      with cleft lip and palate was 66.6%; the prevalence of these findings in females
      was 75% and 61.9% in males. The total prevalence of tonsilloliths was 7.5%.
      CONCLUSION: It is important to ascertain calcification of the stylohyoid complex
      and tonsilloliths in the radiological report, due to the anatomical proximity and
      similarsymptomatology to other orofacial impairments inindividuals with cleft lip
      and palate, focusing on females with oral cleft formation, patients with incisive
      trans foramen cleft and incisive post foramen cleft because they are more
      prevalent. Greater knowledge of the anatomical morphometry of individuals with
      cleft lip and palate greatly contributes towards the selection of clinical
      behaviours and the quality of life of these patients, since cleft lip and
      palateis one of the most common anomalies.

PMID- 29174956
TI  - Pristinamycin-induced leukocytoclastic vasculitis: First report of a case in
      Tunisia.

PMID- 29174957
TI  - Alternatives to Testosterone Therapy: A Review.
AB  - INTRODUCTION: Although testosterone therapy (TTh) is an effective treatment for
      hypogonadism, recent concerns regarding its safety have been raised. In 2015, the
      US Food and Drug Administration issued a warning about potential cardiovascular
      risks resulting from TTh. Fertility preservation is another reason to search for
      viable alternative therapies to conventional TTh, and in this review we evaluate
      the literature examining these alternatives. AIMS: To review the role and
      limitations of non-testosterone treatments for hypogonadism. METHODS: A
      literature search was conducted using PubMed to identify relevant studies
      examining medical and non-medical alternatives to TTh. Search terms included
      hypogonadism, testosterone replacement therapy, testosterone therapy,
      testosterone replacement alternatives, diet and exercise and testosterone,
      varicocele repair and testosterone, stress reduction and testosterone, and sleep
      apnea and testosterone. MAIN OUTCOME MEASURES: Review of peer-reviewed
      literature. RESULTS: Medical therapies examined include human chorionic
      gonadotropins, aromatase inhibitors, and selective estrogen receptor modulators.
      Non-drug therapies that are reviewed include lifestyle modifications including
      diet and exercise, improvements in sleep, decreasing stress, and varicocele
      repair. The high prevalence of obesity and metabolic syndrome in the United
      States suggests that disease modification could represent a viable treatment
      approach for affected men with hypogonadism. CONCLUSIONS: These alternatives to
      TTh can increase testosterone levels and should be considered before TTh. Lo EM,
      Rodriguez KM, Pastuszak AW, Khera M. Alternatives to Testosterone Therapy: A
      Review. Sex Med Rev 2018;6:106-113.

PMID- 29174958
TI  - Plant phenolics and terpenoids as adjuvants of antibacterial and antifungal
      drugs.
AB  - BACKGROUND: The intensive use of antibacterial and antifungal drugs has
      dramatically increased the microbial resistance and has led to a higher number of
      difficult-to-eradicate infections. Combination therapy with two or more
      antimicrobial drugs has emerged some years ago to overcome the issue, but it has
      proven to be not completely effective. Natural secondary metabolites of MW <= 500
      represent promising adjuvants for antimicrobials and have been the object of
      several researches that have increased in the last two decades. PURPOSE: The
      purpose of this Review is to do a literature search of the natural compounds that
      showed high enhancing capacity of antibacterials' and antifungals' effects
      against planktonic bacteria and fungi and to analyze which are the natural
      products most used in combination with a focus on polyphenols and terpenoids.
      RESULTS: One hundred of papers were collected for reviewing. Fifty six (56) of
      them deal with combinations of low MW natural products with antibacterial drugs
      against planktonic bacteria and forty four (44) on natural products with
      antifungal drugs against planktonic fungi. Of the antibacterial adjuvants, 41
      (73%) were either polyphenols (27; 48%) or terpenes (14; 25%). The remaining 15
      papers (27%), deal with different class of natural products. Since most natural
      potentiators belong to the terpene or phenolic structural types, a more detailed
      description of the works dealing with these type of compounds is provided here.
      Bacterial and fungal resistance mechanisms, the modes of action of the main
      classes of antibacterial and antifungal drugs and the methodologies most used to
      assess the type of interactions in the combinations were included in the Review
      too. CONCLUSIONS AND PERSPECTIVES: Several promising results on the potentiation
      effects of antifungals' and antibacterials' activities by low MW natural products
      mainly on polyphenols and terpenes were reported in the literature and, in spite
      of that most works included only in vitro assays, this knowledge opens a wide
      range of possibilities for the combination antimicrobial therapy. Further
      research including in vivo assays and clinical trials are required to determine
      the relevance of these antimicrobial enhancers in the clinical area and should be
      the focus of future studies in order to develop new antimicrobial combination
      agents that overpass the drawbacks of the existing antibiotics and antifungals in
      clinical use.

PMID- 29174959
TI  - Blind versus ultrasound-guided maxillary nerve block in donkeys.
AB  - OBJECTIVES: To describe the 'blind' and ultrasound-guided approaches to block the
      maxillary nerve in donkeys. To compare the success and complication rates between
      the 'blind' and ultrasound-guided techniques based on staining of nerves and
      other structures in cadavers and assessing level of analgesia in live animals.
      STUDY DESIGN: Prospective anatomical and experimental study. ANIMALS: Eighteen
      cadaver heads and nine adult live donkeys. METHODS: Phase 1: the anatomical
      characteristics of the maxillary nerve and its related structures were
      investigated within the pterygopalatine fossa in five cadavers. Phase 2: 0.1 mL
      of methylene blue dye was injected blindly and via ultrasound guidance in 13
      cadavers to stain the left and right maxillary nerves, respectively. Nerve
      staining and dye spreading were evaluated through cadaver dissection. Phase 3:
      the former procedures were applied in nine live donkeys using lidocaine
      hydrochloride 2% and the onset of analgesia was verified through needle pricking
      at the naris. RESULTS: Ultrasound-guided deposition of methylene blue dye in
      cadavers and lidocaine injection in live animals were successful in all instances
      (accuracy = 100%) without inadvertent vascular penetration. Using the 'blind'
      technique, misdirection and intravascular deposition of dye were reported in four
      cadavers (accuracy = 69.2%) and neurovascular trauma was observed in live donkeys
      (five cases). Loss of cutaneous sensation in the ipsilateral naris was earlier in
      the ultrasound-guided approach (10.9 +/- 1.8 minutes) than in the 'blind'
      technique (27.8 +/- 3.2 minutes; p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE:
      An ultrasound-guided maxillary nerve blockade proved very practical and can be
      used to block the maxillary nerve with a high degree of accuracy while avoiding
      vascular penetration. Further studies are mandatory to validate its analgesic
      effectiveness in clinical situations.

PMID- 29174960
TI  - The uptake of transdermal fentanyl in a pregnant sheep model.
AB  - OBJECTIVE: To evaluate the maternal and foetal uptake of transdermal fentanyl
      patch applied to the groin of pregnant sheep following surgery. STUDY DESIGN:
      Prospective series. ANIMALS: A group of 16 singleton pregnant sheep underwent
      anaesthesia for laparotomy, hysterotomy and instrumentation of the foetus. Of
      these ewes 10 (101 +/- 12 days of gestation) were used to evaluate the maternal
      uptake of transdermal fentanyl, and the efficacy of the drug in the postoperative
      period (n = 10). To determine the extent of transplacental transfer of fentanyl,
      six ewes from the group of 10, and six other ewes (92 +/- 1 days' gestation) were
      studied. METHODS: A 75 MUg hour-1 fentanyl patch was placed onto the woolless
      skin of the medial thigh close to the groin at the end of surgery. Maternal blood
      samples were collected from the cephalic or jugular vein, and pain and sedation
      scores were determined, prior to application of the patch (time 0) and at 3, 6,
      12, 24, 36 and 48 hours after. A commercial Fentanyl ELISA kit was used to
      determine the concentration of fentanyl. Paired maternal and foetal blood samples
      were collected 48 hours after surgery. Animals were euthanized at the end of the
      study. Data were tested for normality and compared with Student t test or one-way
      anova and are expressed as mean +/- standard deviation or median (range).
      RESULTS: Recovery from anaesthesia and surgery was uneventful in all ewes. The
      dose of fentanyl was 1.4 +/- 0.2 MUg kg-1 hour-1. The maximum maternal plasma
      concentration of fentanyl was 0.547 ng mL-1 (range, 0.349-0.738 ng mL-1) at 12
      hours. After 48 hours, the concentration of fentanyl was 0.381 ng mL-1 (range,
      0.211-0.487 ng mL-1; maternal) and 0.295 ng mL-1 (range, 0.185-0.377 ng mL-1;
      foetal; p = 0.175). The placental transfer rate of fentanyl was 77%. CONCLUSIONS
      AND CLINICAL RELEVANCE: The uptake of fentanyl varied between animals. The
      placental transfer rate of fentanyl was 77%.

PMID- 29174961
TI  - Effect of premedication with butorphanol or methadone on ease of endoscopic
      duodenal intubation in dogs.
AB  - OBJECTIVE: The effect of premedication with butorphanol or methadone on ease of
      endoscopic duodenal intubation. STUDY DESIGN: Prospective, randomized, blinded
      clinical trial. ANIMALS: A group of 20 client-owned dogs. METHODS: Dogs were
      assigned randomly to be administered intravenous (IV) premedication with either
      butorphanol (0.4 mg kg-1) or methadone (0.3 mg kg-1). General anaesthesia was
      induced with propofol to effect and maintained with isoflurane in 100% oxygen.
      Sedation score 20 minutes after premedication administration and induction dose
      of propofol were recorded. Heart rate, mean arterial pressure, haemoglobin oxygen
      saturation, respiratory rate and end-tidal isoflurane concentration were recorded
      every 5 minutes. Spontaneous lower oesophageal and pyloric sphincter opening,
      presence of gastro-oesophageal and duodeno-gastric reflux, antral peristaltic
      contractions and response to endoscopy were recorded as yes or no. Ease of
      duodenal intubation (EDI) was graded on a scale ranging from 1 (immediate entry
      with minimal manoeuvring required) to 4 (no entry after 2 minutes). Time
      (seconds) from the start of pyloric intubation to successfully entering the
      duodenum was recorded. RESULTS: Median EDI score [3 +/- 1 (butorphanol), 4 +/- 1
      (methadone), p = 0.035], time [65 +/- 36 seconds (butorphanol), 120 +/- 38
      seconds (methadone), p = 0.028] and number of dogs with spontaneous pyloric
      sphincter opening [7/10 (butorphanol), 2/10 (methadone), p = 0.035] differed
      between groups. No other significant differences were found. CONCLUSIONS AND
      CLINICAL RELEVANCE: In these clinical cases, duodenal intubation was performed
      with greater ease, shorter time and more frequent spontaneous opening of the
      pyloric sphincter after premedication with butorphanol in comparison to
      methadone. The use of butorphanol facilitated the passage of the endoscope and is
      therefore recommended for premedication prior to upper gastrointestinal tract
      endoscopy.

PMID- 29174962
TI  - The use of atracurium in an anaesthetized ring-tailed lemur (Lemur catta).

PMID- 29174963
TI  - Diagnosis, pathophysiology, and management of cluster headache.
AB  - Cluster headache is a trigeminal autonomic cephalalgia characterised by extremely
      painful, strictly unilateral, short-lasting headache attacks accompanied by
      ipsilateral autonomic symptoms or the sense of restlessness and agitation, or
      both. The severity of the disorder has major effects on the patient's quality of
      life and, in some cases, might lead to suicidal ideation. Cluster headache is now
      thought to involve a synchronised abnormal activity in the hypothalamus, the
      trigeminovascular system, and the autonomic nervous system. The hypothalamus
      appears to play a fundamental role in the generation of a permissive state that
      allows the initiation of an episode, whereas the attacks are likely to require
      the involvement of the peripheral nervous system. Triptans are the most effective
      drugs to treat an acute cluster headache attack. Monoclonal antibodies against
      calcitonin gene-related peptide, a crucial neurotransmitter of the trigeminal
      system, are under investigation for the preventive treatment of cluster headache.
      These studies will increase our understanding of the disorder and perhaps reveal
      other therapeutic targets.

PMID- 29174964
TI  - microRNA-212 promotes lipid accumulation and attenuates cholesterol efflux in THP
      1 human macrophages by targeting SIRT1.
AB  - Macrophage foam cell formation is a key initiating event in the pathogenesis of
      atherosclerosis. This work was conducted to determine the role of microRNA (miR)
      212 in the transformation of foam cells from macrophages. We examined the
      expression of miR-212 in atherosclerotic lesions in an apoE-deficient (apoE-/-)
      mouse model. The effects of miR-212 overexpression and knockdown on lipid
      accumulation and cholesterol homeostasis in THP-1 macrophages after exposure to
      oxidized low-density lipoprotein (oxLDL). The mechanism underlying the activity
      of miR-212 was explored. It was found that miR-212 was downregulated in
      atherosclerotic lesions and macrophages from apoE-/- mice fed high-fat diet,
      compared to the equivalents from apoE-/- mice fed standard diet. Overexpression
      of miR-212 promoted lipid accumulation in oxLDL-treated THP-1 macrophages,
      whereas miR-212 depletion exerted an opposite effect. Macrophage cholesterol
      efflux to apolipoprotein A-I was significantly reduced by miR-212, which was
      accompanied by reduced ABCA1 expression. Mechanistically, miR-212 targeted
      sirtuin 1 (SIRT1) to repress the expression of ABCA1 in THP-1 macrophages. Rescue
      experiments confirmed that co-expression of SIRT1 attenuated lipid accumulation
      and restored cholesterol efflux in miR-212-overexpressing THP-1 macrophages.
      Collectively, miR-212 facilitates macrophage foam cell formation and suppresses
      ABCA1-dependent cholesterol efflux through downregulation of SIRT1. Targeting miR
      212 may provide a potential therapeutic strategy for atherosclerosis.

PMID- 29174965
TI  - IL-6 release of Rv0183 antigen-stimulated whole blood is a potential biomarker
      for active tuberculosis patients.
AB  - OBJECTIVE: New tests for diagnosing active tuberculosis (aTB) are urgently
      needed, and TB antigen-specific cell-mediated immunity can be expected to develop
      new testing methods of aTB. MATERIALS AND METHODS: Rv0183 protein, the only
      monoglyceride lipase identified in mycobacteria, was used to stimulate freshly
      heparin-treated whole blood. The Rv0183-specific cytokines/chemokines response
      associated with aTB was screened firstly with 4 aTB patients and 4 LTBIs, and
      further evaluated in 192 suspected aTB patients and 372 healthy individuals.
      RESULTS: Out of 71 cytokines/chemokines, the response of IL-6 against Rv0183
      protein was found to be associated with aTB. The Rv0183-specific IL-6 response
      was significantly higher in aTB patients (n = 128) than in those with non-TB lung
      disease (n = 64) and in healthy individuals (n = 327) (p < 0.0001), and not
      affected by latent TB infection. In IGRA+ suspected active TB patients, the
      sensitivity, specificity, PPV and NPV of IL-6 response (with cutoff of 235.2
      pg/ml) were 85.7%, 100%, 100% and 51.5% for diagnosing aTB, respectively. While
      in IGRA- ones, they were 87.5%, 80.5%, 60.9% and 95.0% with 174.2 pg/ml IL-6
      response as cutoff, respectively. CONCLUSIONS: These results clearly show that
      the Rv0183 antigen-specific IL-6 response has the potential to be used as an
      immune-diagnosis test for active TB in clinical practice.

PMID- 29174966
TI  - Pentraxin-3 as a marker of sepsis severity and predictor of mortality outcomes: A
      systematic review and meta-analysis.
AB  - OBJECTIVES: Pentraxin-3 (PTX-3) is a multi-functional pattern recognition
      molecule produced by various cell types of peripheral tissues in different
      infections. It is raised in sepsis, but its values in predicting disease severity
      or mortality outcomes have been controversial. Therefore, we conducted a
      systematic review and meta-analysis of these associations. METHODS: PubMed and
      Embase were searched until July 18, 2017 for studies that evaluated the
      relationship between PTX-3 levels and disease severity or mortality in sepsis.
      RESULTS: A total of 23 and 10 entries were retrieved from both databases,
      respectively, of which 16 studies were included in the final meta-analysis. A
      total of 3001 patients (56% male, mean age 63 +/- 15 years; mean follow-up
      duration of 207 days) were analysed. PTX-3 was significantly higher in patients
      with more severe sepsis compared to those with less severe sepsis (standard mean
      difference = 18.5 ng/mL, standard error: 4.5 ng/mL, P < 0.0001) and higher in non
      survivors compared to survivors (standard mean difference = 40.3 ng/mL, standard
      error: 6.8 ng/mL, P < 0.0001). Elevated PTX-3 levels significantly increased the
      risk of all-cause mortality (hazard ratio: 1.91, 95% CI: 1.53 to 2.46, P <
      0.0001). CONCLUSIONS: PTX-3 significantly predicts disease severity and mortality
      in sepsis.

PMID- 29174967
TI  - False positive serum levels of (1-3)-beta-D-Glucan after infusion of intravenous
      immunoglobulins and time to normalisation.
AB  - OBJECTIVES: (1-3)-beta-D-Glucan (BDG) is a marker for invasive fungal diseases
      (IFD). Administration of intravenous immunoglobulin preparations (IVIG) has been
      reported to lead to false positive BDG serum levels >80 pg/ml. The aim of the
      study was to determine the time interval between IVIG infusion and normalisation
      of BDG serum levels. METHODS: In 22 paediatric haemato-/oncologic patients, we
      analysed 92 BDG serum levels obtained within 4 weeks after IVIG administration
      (0.5 to 1 g/kg body weight), correlated them to 54 IVIG episodes and compared
      them to 76 BDG levels obtained in 29 patients without IVIG administration in the
      4 weeks prior to BDG analyses (control group). RESULTS: BDG peak levels within 3
      days after IVIG ranged from 21.47 to 660.38 (median 201.4) pg/ml. BDG serum
      levels at 7, 14 and 21 days (+/-1 day each) after IVIG infusion were
      significantly higher than BDG serum levels in the control group (p < 0.001 each).
      By days 7, 14, and 21 (+/-1 day each) after IVIG infusion, BDG serum levels have
      normalized (<80 pg/ml) in 64.0%, 76.5% and 100%, respectively. CONCLUSIONS: IVIG
      administration leads to false positive BDG levels in the vast majority of
      patients. Elevated BDG levels may be detectable for more than two weeks after
      IVIG administration, while BDG levels normalized within 3 weeks in all patients.
      Therefore, BDG should not be used to diagnose IFD within three weeks after IVIG
      administration.

PMID- 29174968
TI  - Caloric restriction can improve learning and memory in C57/BL mice probably via
      regulation of the AMPK signaling pathway.
AB  - Caloric restriction (CR) is effective in slowing aging and delaying aging-related
      diseases in many species, but the mechanism is complex and not fully elucidated.
      This study aimed to evaluate the beneficial effects of a caloric restriction diet
      on learning and memory, and further to elucidate the mechanisms. Thirty-six week
      old male C57/BL mice were randomly divided into three groups: normal control (NC
      group), high-energy (HE group) and CR group. After 44weeks, the Morris water maze
      was used to examine learning and memory abilities. Western blotting and
      immunohistochemistry were used to detect changes in proteins involved in the
      adenosine monophosphate-activated protein kinase (AMPK) pathway in the mouse
      hippocampus. Compared with NC group, the swimming distance and escape latency
      were shorter in the CR group. The protein and mRNA expression of AMPK and glucose
      transporter type 4 (GLUT4) in the CR group were significantly higher than that in
      HE group. CR increased serum insulin-like growth factor, adiponectin and vaspin,
      decreased blood glucose and serum malondialdehyde, and improved insulin
      sensitivity. Our findings demonstrate that a CR diet may improve hippocampus
      dependent spatial learning ability of C57/BL mice, accompanied with an increase
      in AMPK and GLUT4 expression, which indicates AMPK pathway was associated with
      the neuroprotective effect of CR in mice.

PMID- 29174969
TI  - Resveratrol modulates response against acute inflammatory stimuli in aged mouse
      brain.
AB  - With upcoming age, the capability to fight against harmful stimuli decreases and
      the organism becomes more susceptible to infections and diseases. Here, the
      objective was to demonstrate the effect of dietary resveratrol in aged mice in
      potentiating brain defenses against LipoPolySaccharide (LPS). Acute LPS injection
      induced a strong proinflammatory effect in 24-months-old C57/BL6 mice hippocampi,
      increasing InterLeukin (Il)-6, Tumor Necrosis Factor-alpha (Tnf-alpha), Il-1beta,
      and C-X-C motif chemokine (Cxcl10) gene expression levels. Resveratrol induced
      higher expression in those cytokines regarding to LPS. Oxidative Stress (OS)
      markers showed not significant changes after LPS or resveratrol, although for
      resveratrol treated groups a slight increment in most of the parameters studies
      was observed, reaching signification for NF-kB protein levels and iNOS
      expression. However, Endoplasmic Reticulum (ER) stress markers demonstrated
      significant changes in resveratrol-treated mice after LPS treatment, specifically
      in eIF2alpha, BIP, and ATF4. Moreover, as described, resveratrol is able to
      inhibit the mechanistic Target of Rapamycin (mTOR) pathway and this effect could
      be linked to (eIF2alpha) phosphorylation and the increase in the expression of
      the previously mentioned proinflammatory genes as a response to LPS treatment in
      aged animals. In conclusion, resveratrol treatment induced a different cellular
      response in aged animals when they encountered acute inflammatory stimuli.

PMID- 29174970
TI  - Selective isolation and noninvasive analysis of circulating cancer stem cells
      through Raman imaging.
AB  - Circulating cancer stem cells (CCSCs), a rare circulating tumor cell (CTC) type,
      recently arose as a useful resource for monitoring and characterizing both
      cancers and their metastatic derivatives. However, due to the scarcity of CCSCs
      among hematologic cells in the blood and the complexity of the phenotype
      confirmation process, CCSC research can be extremely challenging. Hence, we
      report a nanoparticle-mediated Raman imaging method for CCSC characterization
      which profiles CCSCs based on their surface marker expression phenotypes. We have
      developed an integrated combinatorial Raman-Active Nanoprobe (RAN) system
      combined with a microfluidic chip to successfully process complete blood samples.
      CCSCs and CTCs were detected (90% efficiency) and classified in accordance with
      their respective surface marker expression via completely distinct Raman signals
      of RANs. Selectively isolated CCSCs (93% accuracy) were employed for both in
      vitro and in vivo tumor phenotyping to identify the tumorigenicity of the CCSCs.
      We utilized our new method to predict metastasis by screening blood samples from
      xenograft models, showing that upon CCSC detection, all subjects exhibited liver
      metastasis. Having highly efficient detection and noninvasive isolation
      capabilities, we have demonstrated that our RAN-based Raman imaging method will
      be valuable for predicting cancer metastasis and relapse via CCSC detection.
      Moreover, the exclusion of peak overlapping in CCSC analysis with our Raman
      imaging method will allow to expand the RAN families for various cancer types,
      therefore, increasing therapeutic efficacy by providing detailed molecular
      features of tumor subtypes.

PMID- 29174971
TI  - A self-powered biosensing device with an integrated hybrid biofuel cell for
      intermittent monitoring of analytes.
AB  - In this work, we propose an integrated self-powered sensing system, driven by a
      hybrid biofuel cell (HBFC) with carbon paper discs coated with multiwalled carbon
      nanotubes. The sensing system has a biocathode made from laccase or bilirubin
      oxidase, and the anode is made from a zinc plate. The system includes a dedicated
      custom-built electronic control unit for the detection of oxygen and catechol
      analytes, which are central to medical and environmental applications. Both the
      HBFC and sensors, operate in a mediatorless direct electron transfer mode. The
      measured characteristics of the HBFC with externally applied resistance included
      the power-time dependencies under flow cell conditions, the sensors performance
      (evaluated by cyclic voltammetry), and chronoamperometry. The HBFC is integrated
      with analytical devices and operating in a pulse mode form long-run monitoring
      experiments. The HBFC generated sufficient power for wireless data transmission
      to a local computer.

PMID- 29174972
TI  - A novel electrochemical sensor based on Cu@Ni/MWCNTs nanocomposite for
      simultaneous determination of guanine and adenine.
AB  - A novel electrochemical sensing platform based on combination of multi-walled
      carbon nanotubes and copper-nickel hybrid nanoparticles (Cu@Ni/MWCNTs) was
      developed for simultaneous detection of guanine (G) and adenine (A). The
      Ni/MWCNTs and Cu@Ni/MWCNTs nanocomposites were characterized by transmission
      electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). The
      electrochemical behaviors of G and A on the modified electrode were explored by
      cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in phosphate
      buffer with pH 3.0. Under the optimal conditions, electrical signals were linear
      over the concentration ranges from 5.0 to 180MUM and 8.0 to 150MUM for
      simultaneous determination G and A with the detection limit as low as 0.35MUM and
      0.56MUM (S/N = 3), respectively. Furthermore, linear concentration ranges in
      individual determination are 1.0-180MUM and 2.0-150MUM with detection limits of
      0.17MUM and 0.33MUM (S/N = 3) for G and A, respectively. The sensor was
      successfully used to quantify G and A in real samples. The Cu@Ni/MWCNTs composite
      presented here can serve as a promising candidate for developing electrochemical
      sensor devices and plays an important role in widespread fields.

PMID- 29174973
TI  - A novel screen-printed mast cell-based electrochemical sensor for detecting
      spoilage bacterial quorum signaling molecules (N-acyl-homoserine-lactones) in
      freshwater fish.
AB  - A novel screen-printed cell-based electrochemical sensor was developed to assess
      bacterial quorum signaling molecules, N-acylhomoserine lactones (AHLs). Screen
      printed carbon electrode (SPCE), which possesses excellent properties such as low
      cost, disposable and energy-efficient, was modified with multi-walled carbon
      nanotubes (MWNTs) to improve electrochemical signals and enhance the sensitivity.
      Rat basophilic leukemia (RBL-2H3) mast cells encapsulated in alginate/graphene
      oxide (NaAgl/GO) hydrogel were immobilized on the MWNTs/SPCE to serve as
      recognition element. Electrochemical impedance spectroscopy (EIS) was employed to
      record the cell impedance signal as-influenced by Pseudomonas aeruginosa quorum
      sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC12-HSL). Experimental
      results show that 3OC12-HSL caused a significant decrease in cell viability in a
      dose dependent manner. The EIS value decreased with concentrations of 3OC12-HSL
      in the range of 0.1-1MUM, and the detection limit for 3OC12-HSL was calculated to
      be 0.094MUM. These results were confirmed via cell viability, SEM, TEM analysis.
      Next, the sensor was successfully applied to monitoring the production of AHLs by
      spoilage bacteria in three different freshwater fish juice samples which
      efficiently proved the practicability of this cell based method. Therefore, the
      proposed cell sensor may serve as an innovative and effective approach to the
      measurement of quorum signaling molecule and thus provides a new avenue for real
      time monitoring the spoilage bacteria in freshwater fish production.

PMID- 29174974
TI  - m-Trifluoromethyl-diphenyl diselenide promotes resilience to social avoidance
      induced by social defeat stress in mice: Contribution of opioid receptors and
      MAPKs.
AB  - Depressive symptoms precipitated by stress are prevalent in population. In
      experimental models of social stress, endogenous opioids mediate different
      aspects of defensive and submissive behaviors. The present study investigated the
      opioid receptors, mitogen-activated protein kinase (MAPKs) and protein kinase B
      (Akt) contribution to m-trifluoromethyl-diphenyl diselenide [(m-CF3-PhSe)2]
      effects on social avoidance induced by social defeat stress (SDS). Adult Swiss
      mice were subjected to SDS and treated with (m-CF3-PhSe)2 (5 to 25mg/kg) for
      7days. After that, the mice performed locomotor and social avoidance tests. The
      opioid receptors, MAPKs and Akt protein contents were determined in the
      prefrontal cortical samples of mice. Firstly, the mice were segregated in
      susceptible or resilient subpopulation based on their social avoidance induced by
      stress. (m-CF3-PhSe)2 (25mg/kg) was effective against the stress-induced social
      avoidance and improved social interaction behavior in mice. SDS increased the MU
      and kappa protein contents but reduced those of delta opioid receptors in
      susceptible mice. Resilient and (m-CF3-PhSe)2-treated mice had no alteration in
      the levels of opioid receptors. Moreover, (m-CF3-PhSe)2 was effective against the
      increase of c-Jun N-terminal kinase (JNK) and the decrease of Akt phosphorylation
      protein contents induced by SDS in susceptible mice. The protein content of
      extracellular signal-regulated kinase (ERK) phosphorylation was reduced in both
      susceptible and resilient mice, whereas p38 mitogen-activated protein kinase (p38
      MAPK) phosphorylation was increased only in resilient mice. (m-CF3-PhSe)2 was
      partially effective against the pERK decrease and ineffective against the
      increase in p38 MAPK phosphorylation in mice subjected to SDS. These results
      suggest that the modulation of protein contents of opioid receptors, JNK and Akt
      phosphorylation is associated with resilience to SDS promoted by (m-CF3-PhSe)2 in
      mice.

PMID- 29174975
TI  - Consumers' perceptions of biocidal products in households.
AB  - Biocidal products are commonly used in households and can pose a risk to human
      health and the environment. The aim of this study was to evaluate consumers' use
      and understanding of biocidal products in order to identify starting points for
      minimising their exposure to these products and reducing possible emissions to
      the environment. In a case study, standardised questionnaires were used to
      interview consumers in 133 households in three neighbourhoods in Northern
      Germany, representing the urban-rural typologies in Europe: predominantly urban,
      intermediate and predominantly rural regions. The questions focussed on the
      comprehension of the term 'biocide', pest control habits, sources of information,
      risk perception of different product groups and possible emission reduction
      measures. Only 21% of the respondents understood the term 'biocide' correctly,
      whereas 29% thought of 'something that had to do with organic pest control', and
      28% were not able to think of a possible meaning. The risk perception of biocidal
      products compared to plant protection products varied depending on the living
      conditions. In the urban neighbourhood, biocidal products were perceived as more
      dangerous than in the rural area. The main pests to be fought were ants, mould
      and fruit fly. The results of the study indicate that there is a considerable
      difference between the types of biocidal products that interviewees claimed to
      own and those that they actually did have in their households. Most notably,
      respondents did not realise that they owned surface disinfectants. This result
      indicates that consumers often seem not to be aware of using specific biocidal
      products. Also, this shows the limitations of collecting data on products owned
      with only one method, as the results from products inventories of the households
      deviate from the data collected in interviews. Our results show that the term
      'biocide' is not fully understood by many people. To communicate possible risks
      of biocidal products, other terms would have to be used. Online information
      regarding general facts on necessary general hygiene measures and biocidal
      products against bacteria and insects are likely to be of highest relevance for
      consumers. However, risk communication for biocidal products in general is
      difficult because consumers are often not aware of using biocidal products. For
      this reason, information and awareness raising campaigns should be accompanied by
      further measures such as sales restrictions for specific user-groups or
      prohibitions of certain uses for a sustainable use of biocidal products.

PMID- 29174976
TI  - Deposition pattern of aerosolized Legionella using an ex vivo human-porcine
      respiratory model.
AB  - Legionella are bacteria responsible for severe lung pathologies. However how they
      enter and are deposited within the respiratory tract remains poorly documented.
      Data using animal testing led to the establishment of mathematical models
      allowing the estimation of aerosol dispersion risks. But direct extrapolation to
      humans is questionable and experimental models more physiologically
      representative of the inhalation route are welcome. The aim of this study was to
      develop a model as close as possible to the human anatomy and physiology allowing
      determining the deposition pattern of aerosolized Legionella while limiting in
      vivo experiments. To that purpose, we adapted the chimeric respiratory tract
      model we previously developed. This original model consisted of a replica of the
      human upper respiratory airways made by additive manufacturing connected to ex
      vivo porcine lungs ventilated by passive expansion, as for humans in
      physiological conditions. These experiments didn't imply specific animal
      sacrifices as pigs were bred for human consumption and lungs were considered as
      wastes by the slaughterhouse. Fluorescent Legionella were aerosolized and
      visualized using Cellvizio(r) Lab (probe-based confocal fluorescence microscope).
      Legionella were found in the whole respiratory tract. Broncho-alveolar lavages
      were also performed and the amount of Legionella reaching the thoracic region was
      quantified by culture and qPCR. Legionella were found preferentially in the left
      upper lobe compared to the right lower lobe. To our knowledge, it is the first
      time that experiments mimicking so closely human exposure by inhalation are
      performed while limiting animal experiments and providing a model for further
      Legionella infectious risk assessment.

PMID- 29174977
TI  - Generation of an induced pluripotent stem cell line from a 39-year-old female
      patient with severe-to-profound non-syndromic sensorineural hearing loss and a
      A1555G mutation in the mitochondrial MTRNR1 gene.
AB  - Sensorineural hearing loss (SNHL) is a prevalent form of deafness commonly
      arising from damage to the cochlear sensory hair cells and degeneration of the
      spiral ganglion neurons. In this study, Sendai virus was used to generate an
      induced pluripotent stem cell (iPSC) line from a 39-year-old female patient
      diagnosed with severe-to-profound, non-syndromic SNHL. The patient also carries a
      A1555G mutation in the mitochondrial 12S ribosome RNA gene (MTRNR1). This iPSC
      line was verified to express pluripotent markers, possess normal karyotype,
      harbor the specific mutation and demonstrated the capacity to differentiate into
      three germ layers.

PMID- 29174978
TI  - Transcription pausing regulates mouse embryonic stem cell differentiation.
AB  - The pluripotency of embryonic stem cells (ESCs) relies on appropriate
      responsiveness to developmental cues. Promoter-proximal pausing of RNA polymerase
      II (Pol II) has been suggested to play a role in keeping genes poised for future
      activation. To identify the role of Pol II pausing in regulating ESC
      pluripotency, we have generated mouse ESCs carrying a mutation in the pause
      inducing factor SPT5. Genomic studies reveal genome-wide reduction of paused Pol
      II caused by mutant SPT5 and further identify a tight correlation between pausing
      mediated transcription effect and local chromatin environment. Functionally, this
      pausing-deficient SPT5 disrupts ESC differentiation upon removal of self-renewal
      signals. Thus, our study uncovers an important role of Pol II pausing in
      regulating ESC differentiation and suggests a model that Pol II pausing
      coordinates with epigenetic modification to influence transcription during mESC
      differentiation.

PMID- 29174979
TI  - MicroRNA-30e-5p suppresses non-small cell lung cancer tumorigenesis by regulating
      USP22-mediated Sirt1/JAK/STAT3 signaling.
AB  - MicroRNA-30e-5p (miR-30e-5p) is a tumor suppressor that is known to be
      downregulated in non-small cell lung cancer (NSCLC). However, how miR-30e-5p
      inhibits NSCLC tumorigenesis is not known. Ubiquitin-specific peptidase 22
      (USP22) is upregulated in NSCLC and promotes tumorigenesis via a Sirt1-JAK-STAT3
      pathway. In this study, we investigated whether miR-30e-5p inhibits tumor growth
      by targeting USP22 in NSCLC. Our results reveal that miR-30e-5p expression was
      correlated negatively with USP22 in NSCLC tissues. Luciferase reporter assays
      showed that miR-30e-5p negatively regulated USP22 expression by binding to a
      specific sequence in the 3'UTR. MiR-30e-5p overexpression and USP22 knockdown
      significantly inhibited tumor growth in vivo and induced cell cycle arrest and
      apoptosis in NSCLC cells in vitro. The effects of miR-30e-5p inhibition were
      prevented by USP22 knockdown. MiR-30e-5p inhibited SIRT1 expression and increased
      expression of p53 and the phosphorylated form of STAT3 (pSTAT3). Furthermore, miR
      30e-5p prevented USP22-mediated regulation of SIRT1, pSTAT3, and p53 expression.
      Taken together, these findings suggest that miR-30e-5p suppresses NSCLC
      tumorigenesis by downregulatingUSP22-mediated Sirt1/JAK/STAT3 signaling. Our
      study has identified miR-30e-5p as a potential therapeutic target for the
      treatment of NSCLC.

PMID- 29174980
TI  - PDGF-mediated PI3K/AKT/beta-catenin signaling regulates gap junctions in corpus
      cavernosum smooth muscle cells.
AB  - Erectile dysfunction (ED) is the most common sexual disorder that men report to
      healthcare providers. Gap junctions (GJs) are thought to be responsible for
      synchronous shrinkage of corpus cavernosum smooth muscle cells (CCSMCs), and play
      thus an important role in the maintenance of an erection. Hypoxia has been
      suggested as a pathological mechanism underlying ED. Here we demonstrate that
      hypoxia increased the expression of platelet-derived growth factor (PDGF) and the
      main GJ component connexin (Cx)43 in CCSMCs. Inhibiting PDGF receptor (PDGFR)
      activity decreased Cx43 expression. Treatment with different concentrations of
      PDGF increased the levels of phosphorylated protein kinase B (AKT), beta-catenin,
      and Cx43, whereas inhibition of PDGFR or activation of phosphatidylinositol 3
      kinase (PI3K)/AKT signaling altered beta-catenin and Cx43 expression. Meanwhile,
      silencing beta-catenin resulted in the downregulation of Cx43. These results
      demonstrate that PDGF secretion by CCSMCs and vascular endothelial cells is
      enhanced under hypoxic conditions, leading to increased Cx43 expression through
      PI3K/AKT/beta-catenin signaling and ultimately affecting GJ function in ED. Thus,
      targeting this pathway is a potential therapeutic strategy for the treatment of
      ED.

PMID- 29174981
TI  - Acetylation of TIP60 at K104 is essential for metabolic stress-induced apoptosis
      in cells of hepatocellular cancer.
AB  - Tumor cells often encounter hypoglycemic microenvironment due to rapid cell
      expansion. It remains elusive how tumors reprogram the genome to survive the
      metabolic stress. The tumor suppressor TIP60 functions as the catalytic subunit
      of the human NuA4 histone acetyltransferase (HAT) multi-subunit complex and is
      involved in many different cellular processes including DNA damage response, cell
      growth and apoptosis. Attenuation of TIP60 expression has been detected in
      various tumor types. The function of TIP60 in tumor development has not been
      fully understood. Here we found that suppressing TIP60 inhibited p53 K120
      acetylation and thus rescued apoptosis induced by glucose deprivation in
      hepatocellular cancer cells. Excitingly, Lys-104 (K104), a previously identified
      lysine acetylation site of TIP60 with unknown function, was observed to be
      indispensable for inducing p53-mediated apoptosis under low glucose condition.
      Mutation of Lys-104 to Arg (K104R) impeded the binding of TIP60 to human NuA4
      complex, suppressed the acetyltransferase activity of TIP60, and inhibited the
      expression of pro-apoptotic genes including NOXA and PUMA upon glucose
      starvation. These findings demonstrate the critical regulation of TIP60/p53
      pathway in apoptosis upon metabolic stress and provide a novel insight into the
      down-regulation of TIP60 in tumor cells.

PMID- 29174982
TI  - CD4+ T cell-mediated cytotoxicity is associated with MHC class II expression on
      malignant CD19+ B cells in diffuse large B cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy with
      approximately 30% of patients present relapsed or refractory disease after first
      line therapy. Research of further treatment options is needed. Cytotoxic CD4+ T
      cells express cytolytic molecules and have potential antitumor function. Here, we
      showed that the CD19+ cells from DLBCL patients presented significantly reduced
      expression of MHC II molecules than those from healthy controls. Three years
      after the first-line treatment, patients that presented relapsed disease had
      significantly lower MHC II expression on their CD19+ cells than patients who did
      not show recurrence. Examining cytotoxic CD4+ T cells show that DLBCL patients
      presented significantly elevated frequencies of granzyme A-, granzyme B-, and/or
      perforin-expressing cytotoxic CD4+ T cells. Also, frequency of cytotoxic CD4+ T
      cells in DLBCL patients was positively correlated with the MHC II expression
      level. Subsequently, the cytotoxic potential of CD4+ T cells against autologous
      CD19+ cells was investigated. We found that the cytotoxic potential of CD4+ T
      cells was highest in MHC II-high, intermediate in MHC II-mid, and lowest in MHC
      II-low patients. The percentage of MHC II-expressing viable CD19+ cells presented
      a significant reduction after longer incubation with cytotoxic CD4+ T cells,
      suggesting that cytotoxic CD4+ T cells preferentially eliminated MHC II
      expressing CD19+ cells. Blocking MHC II on CD19+ cells significantly reduced the
      cytolytic capacity of CD4+ T cells. Despite these discoveries, the frequency of
      cytotoxic CD4+ T cells did not predict the clinical outcome of DLBCL patients.
      Together, these results demonstrated that cytotoxic CD4+ T cells presented an MHC
      II-dependent cytotoxic potential against autologous CD19+ cells and could
      potentially represent a future treatment option for DLBCL.

PMID- 29174983
TI  - Comparison of hepatic transcriptome profiling between acute liver injury and
      acute liver failure induced by acetaminophen in mice.
AB  - Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver
      failure in many countries. In the present study, we developed stable mouse models
      of acute drug-induced hepatic injury (DILI) and acute drug-induced hepatic
      failure (DILF) by sub-lethal and lethal APAP injection respectively. The
      differences in hepatic transcriptome profiling between these two models were
      compared by RNA sequencing, which were validated by qPCR, western-blot and ELISA.
      In results, serum IL-6, TNF-a and IL-10 levels are higher in DILF than in DILI.
      The upregulated genes in DILF compared with DILI were mostly enriched in the
      areas of "cellular development process", "cell division", "multicellular organism
      development," etc. The downregulated genes in DILF compared with DILI were mostly
      enriched in the areas of "cellular response to chemical stimulus", "cellular
      response to stress", "cell activation," etc. Sub-lethal doses of APAP increased
      Myc, Bag3 and Btc expression in mouse liver, but lethal doses of APAP did not,
      which suggested that these three genes might play important roles in adaptive
      protection reactions in DILI. The serum Btc level might be a potential biomarker
      of drug induced liver injury with good prognosis. Our data can help us better
      understand the mechanisms of hepatotoxicity that influence prognosis and seek
      novel prognostic indicators of DILI.

PMID- 29174984
TI  - Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing
      nitrogen mustard-induced injury in ex vivo cultured rabbit cornea.
AB  - Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however,
      there are no effective antidotes available. Using nitrogen mustard (NM), a bi
      functional analog of SM, we have earlier reported that NM-induced corneal injury
      in ex vivo rabbit cornea organ culture model parallels corneal injury reported
      with SM. Using this model, we have demonstrated the therapeutic efficacy of
      dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2h
      exposure)-induced corneal injuries when added immediately after washing NM. In
      the present study, we further examined the efficacy of similar/higher doses of
      these agents when added immediately, 2, or 4h after washing NM following its 2h
      exposure. All three treatment agents caused a reversal in established NM-induced
      injury biomarkers when added immediately or 2h after washing NM following its 2h
      exposure; however, when treatments were carried out 4h after washing NM, there
      was no significant effect. Together, our results further show the beneficial
      effect of these agents in reversing NM-induced corneal injury and indicate the
      time window for effective treatment. This could be useful towards future
      development of targeted therapeutics against vesicant-induced ocular injury.

PMID- 29174985
TI  - Role of P-glycoprotein in deoxynivalenol-mediated in vitro toxicity.
AB  - Deoxynivalenol (DON) is the most prevalent mycotoxin produced by grain-infecting
      Fusarium strains and frequently occurs in small cereals all over the world. After
      ingestion, DON is absorbed in the gut, which leads dose-dependently to critical
      health effects. In the present study, we have further investigated DON's
      previously reported affinity to the efflux transporter P-glycoprotein (Pgp) in
      the apical enterocyte membrane. Interaction with Pgp was studied in human
      colorectal adenocarcinoma (Caco-2) cells and Madin-Darby Canine Kidney wild-type
      (MDCKII-wt) and Pgp-overexpressing (MDCKII-MDR1) cells in different transport and
      cytotoxicity experiments. We found that DON was exported by Pgp and was less
      cytotoxic in Pgp-overexpressing cells. In the fluorometric calcein
      acetoxymethylester (Calcein AM) assay DON reduced intracellular calcein
      retention, indicating a stimulation of Pgp-mediated efflux. In the presence of
      the selective Pgp inhibitors verapamil (Ver) and valspodar (PSC 833) the effect
      was, respectively, distinctive and significant. Verrucarol, a structural analogue
      of DON, was much less effective indicating the importance of the alpha, beta
      conjugated carbonyl group in the DON molecule for Pgp interaction. Our results
      confirmed that Pgp might have the potential to reduce intestinal absorption of
      DON in vivo. Furthermore, we were able to show that DON can modulate Pgp activity
      in vitro.

PMID- 29174986
TI  - Correlation between glucuronidation and covalent adducts formation with proteins
      of nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause idiosyncratic liver
      injury. Mechanisms involved in NSAID-induced liver injury are complex. Previous
      studies have suggested that acyl glucuronide of NSAIDs (NSAIDs-Glu) plays an
      important role in the development of liver injury via covalently binds to
      proteins and the resultant adduct induces immunological toxicity. As only some
      NSAIDs-Glu are commercially available, the evaluation of covalent protein adduct
      formation using ready-made NSAIDs-Glu is difficult and inconvenient. Moreover,
      glucuronidation potency varies with the NSAID, including stereoisomers.
      Therefore, in this study, we simultaneously examined the glucuronidation and
      covalent adduct formation using enantiomers of parent NSAIDs (ibuprofen,
      naproxen, pranoprofen, ketoprofen, and flurbiprofen) in rat liver microsomes.
      Glucuronides and covalent adducts were quantified by HPLC. The amount of covalent
      adduct increased with NSAIDs-Glu formation in the rat liver microsomes in a time
      dependent manner. A significant positive correlation was observed between the AUC
      of NSAIDs-Glu and that of covalent adduct, except ketoprofen. Although ketoprofen
      exhibited the highest glucuronidation rate among the NSAIDs investigated, the
      amount of covalent adduct was similar to that for pranoprofen, which had the
      lowest glucuronidation rate. Thus, it may be difficult for ketoprofen glucuronide
      to covalently bind with proteins in the rat liver microsomes. Our results
      suggested that the amount of glucuronide formed is a key factor in predicting
      covalent bond formation with protein in NSAIDs, in addition to degradability and
      bindability with proteins of NSAIDs-Glu. Further studies are required to confirm
      the relationship between the tendency of glucuronidation and the formation of
      covalent adducts of NSAIDs.

PMID- 29174987
TI  - Drug-excipient compatibility assessment of solid formulations containing
      meloxicam.
AB  - Meloxicam (MLX) is a non-steroidal anti-inflammatory cyclooxygenase (COX)
      inhibitor that is used to relieve inflammation and pain. MLX has a preferential
      affinity for COX-2, which is associated with a lower incidence of
      gastrointestinal side effects. The drug belongs to Class II of the
      Biopharmaceutical Classification System (BCS) in which dissolution is the
      limiting step of its bioavailability. In view of this classification, carrying
      out further studies regarding the compatibility of MLX with excipients and the
      mechanisms and kinetics of its degradation reactions is fundamental because any
      changes would directly influence the quality of the product. The aim of the
      present work is to evaluate solid pharmaceutical formulations containing MLX
      found on the market to define the more suitable excipients to improve the
      stability of the pharmaceutical formulations. Thermal analysis techniques were
      used to characterize and evaluate the compatibility between the drug and the
      excipients present in the market formulations. In the evaluation of its solid
      state kinetics, MLX raw material under inert conditions had a shelf life of
      approximately 6years. In the study of compatibility between the drug and
      excipients, MLX was found to be incompatible with magnesium stearate after DSC
      analysis under binary mixtures, which was confirmed by stress studies and
      chromatographic analyzes.

PMID- 29174988
TI  - Synthesis and characterization of IUdR loaded PEG/PCL/PEG polymersome in mixed
      DCM/DMF solvent: Experimental and molecular dynamics insights into the role of
      solvent composition and star architecture in drug dispersion and diffusion.
AB  - Combined experimental and simulation investigations have provided molecular level
      insights into 5-iodo-2'-deoxyuridine (IUdR) loading behavior for the novel
      PEG/PCL/PEG polymersome-like carriers in mixed dichloromethane/N,N
      dimethylformamide (DCM/DMF) solvent. As with the experiments, a novel approach
      was applied for layer by layer tailoring of polyethylene glycol (PEG) and
      polycaprolactone (PCL) as PEG/PCL/PEG copolymer on the surface of magnetite
      nanoparticles (MNPs) by click chemistry. Experimental results indicated that
      IUdR, as an anti-cancer drug, could be encapsulated up to 80% EE in this
      nanocarrier and could be in-vitro released up to 90% during 120h. Computational
      studies, on the other hand, provide molecular level insights into the optimal
      performance of the carrier in terms of drug "Dispersion" and "Diffusion" patterns
      in equimolar DCM/DMF solvent. Molecular dynamics simulations of the system in
      four distinct solvation scenarios including pure DCM, mixed DCM/DMF, pure DMF and
      water, have proven that while hydrophobic solvents give rise to better
      "dispersion" of drugs, hydrophilic solvents lead for drug molecules to penetrate
      into the carrier and improve "diffusion" properties. Optimal conditions for drug
      encapsulation, as also confirmed through experiments, was observed for mixed
      DCM/DMF solvent in terms of proper diffusion and well dispersion. While drug
      "aggregates" were observed in DCM, poorly stable drug molecules with lowered
      penetrations were observed in pure DMF. Proper release properties with IUdR
      molecules staying on the surface of the carrier was also observed in water. The
      interesting role of the star-linear architecture was further scrutinized through
      distinctions made through analysis of interactions between IUdR molecules with
      "inner" and "outer" PEG sections.

PMID- 29174989
TI  - Adsorption of heavy metals on conventional and nanostructured materials for
      wastewater treatment purposes: A review.
AB  - The problem of water pollution is of a great concern. Adsorption is one of the
      most efficient techniques for removing noxious heavy metals from the solvent
      phase. This paper presents a detailed information and review on the adsorption of
      noxious heavy metal ions from wastewater effluents using various adsorbents -
      i.e., conventional (activated carbons, zeolites, clays, biosorbents, and
      industrial by-products) and nanostructured (fullerenes, carbon nanotubes,
      graphenes). In addition to this, the efficiency of developed materials for
      adsorption of the heavy metals is discussed in detail along with the comparison
      of their maximum adsorption capacity in tabular form. A special focus is made on
      the perspectives of further wider applications of nanostructured adsorbents
      (especially, carbon nanotubes and graphenes) in wastewater treatment.

PMID- 29174990
TI  - Peroxidation and unsaturation indices as potential biomarkers of multifarious
      zinc and copper micro-supplementation in Helix pomatia L.
AB  - The work is a continuation of two previous studies in which biomarker fatty acids
      (12 of 56 FA pools) were analysed in Helix pomatia L. after heterogeneous micro
      supplementation of Zn and Cu (administered in five micro-doses in the form of
      salts and EDTA and lysine chelates). This time, peroxidation (PI) and
      unsaturation coefficients (UI) as biomarker were analysed. These indices were
      calculated based on the FA profile in the foot and hepatopancreas of snails. The
      correlation of frequently used oxidation status indicators of organisms (catalase
      - CAT, glutathione peroxidase - GPx, selenium-dependent peroxidase - se-GPx,
      superoxide dismutase - SOD, glutathione transferase - GST, glutathione reductase 
      GR, glutathione - GSH, carbonyl protein - CP, thiobarbituric acid reactive
      substances - TBARS) with the rarely used UI and PI ratios was analysed. It was
      found that the 12-week micro-exposure to Zn and Cu did not inhibit but rather
      stimulated antioxidative defence at a sufficient level to increase the values of
      peroxidation/unsaturation indices in comparison to the control groups. Induction
      of an opposite process to oxidation of fatty acids was demonstrated. Maximum
      activities and amounts of antioxidants as well as minima of protein and lipid
      decomposition were recorded in groups supplemented with 0.75mg/l Zn and 1.0mg/l
      Cu. The possibility of a direct use of fatty acids as well as
      peroxidation/unsaturation indices as sensitive and reproducible biomarkers of
      exposure and oxidative physiological status in snails was confirmed.

PMID- 29174991
TI  - Heavy metal pollution and health risk assessment of agricultural soils in a
      typical peri-urban area in southeast China.
AB  - Heavy metal pollution in peri-urban areas in China is serious and complex. We
      thus developed an integrated evaluation method to assess heavy metal pollution
      and potential health risk to residents in a typical peri-urban area with diverse
      anthropogenic emission sources and cropping systems. Ecological risk was
      evaluated using Nemerow's synthetical pollution index (Pn) and Potential
      ecological risk index (RI). Then polluted areas and responsible emission sources
      were identified by GIS mapping. Health risk caused by food intake and soil
      exposure was calculated by accounting for the influence of anthropogenic
      emissions and cropping systems. Agricultural soils in the study area were
      polluted by cadmium (Cd), mercury (Hg), lead (Pb), and arsenic (As). High
      concentrations mainly occurred near the mining area and along the roadsides. The
      accumulation of heavy metals in crops followed the order of tea leaves > rice
      grain > vegetables. The hazard index of potential human health risk caused by
      chronic soil exposure and food intake was 15.3, indicating obvious adverse health
      effects. 87.5% of health risk was attributed to food consumption, and
      significantly varied among different cropping systems with the decreasing order
      of rice (10.44) >vegetable (2.86) > tea (0.05). The integrated method of
      ecological and health risk index, which takes consideration of both anthropogenic
      emission and cropping system can provide a practical tool for evaluating of
      agricultural soil in the peri-urban area regrading different risk factors.

PMID- 29174992
TI  - The main factors effecting the efficiency of Zn(II) flotation: Optimum conditions
      and separation mechanism.
AB  - In this study, the effects of chemical conditions on the recovery of Zn(II) and
      water during the ion flotation process were evaluated using a central composite
      design (CCD) of response surface methodology. The optimum effective parameters
      including pH, collector and frother concentration were determined. The results
      showed that the pH and collector concentration were effective factors for the
      efficiency of Zn(II) flotation. The effects of collector and frother
      concentration on the characterization of sublate and the complexation of sodium
      dodecyl sulphate with Zn(II) were studied using scanning electron microscopy
      coupled with energy dispersive X-ray (SEM/EDX) spectroscopy and Fourier transform
      infrared (FTIR) spectroscopy. The results show that foam fractionation occurred
      at a pH of 1.5, 3 and 5.5 and ion flotation at a pH of 8.

PMID- 29174993
TI  - Application of green compost as amendment in an agricultural soil: Effect on the
      behaviour of triasulfuron and prosulfocarb under field conditions.
AB  - Herbicides are essential in agricultural systems for maintaining crop yields, as
      weeds compromise grain production. Furthermore, the application of organic
      amendments to soil is an increasingly frequent agricultural practice for avoiding
      irreversible soil degradation. However, this practice could modify the behaviour
      of the herbicides applied, with implications for their absorption by weeds. This
      study evaluated the dissipation, persistence and mobility of the herbicides
      triasulfuron and prosulfocarb in a sandy clay loam soil unamended and amended
      with green compost (GC) in a field experiment using single or combined commercial
      formulations of both herbicides. The study was carried out in experimental plots
      (eight treatments * three replicates) corresponding to unamended soil and soil
      amended with GC, untreated and treated with the herbicide formulations Logran(r),
      Auros(r) and Auros Plus(r) over 100 days. The half-life (DT50) of triasulfuron
      applied individually was 19.4 days, and increased in the GC-amended soil (46.7
      days) due to its higher adsorption by this soil, although non-significant
      differences between DT50 values were found when it was applied in combination
      with prosulfocarb. Prosulfocarb dissipated faster than triasulfuron under all the
      conditions assayed, but non-significant differences were observed for the
      different treatments. The analysis of the herbicides at different soil depths (0
      50 cm) after their application confirmed the leaching of both herbicides to
      deeper soil layers under all conditions, although larger amounts of residues were
      found in the 0-10 and 10-20 cm layers. The application of GC to the soil
      increased the persistence of both herbicides, and prevented the rapid leaching of
      triasulfuron in the soil, but the leaching of prosulfocarb was not inhibited. The
      influence of single or combined formulations was observed for triasulfuron, but
      not for prosulfocarb. The results obtained highlight the interest of obtaining
      field data to design rational joint applications of GC and herbicides to prevent
      the possible decrease in their effectiveness for weeds or the risk of water
      contamination.

PMID- 29174994
TI  - Learning bundled care opportunities from electronic medical records.
AB  - OBJECTIVE: The traditional fee-for-service approach to healthcare can lead to the
      management of a patient's conditions in a siloed manner, inducing various
      negative consequences. It has been recognized that a bundled approach to
      healthcare - one that manages a collection of health conditions together - may
      enable greater efficacy and cost savings. However, it is not always evident which
      sets of conditions should be managed in a bundled manner. In this study, we
      investigate if a data-driven approach can automatically learn potential bundles.
      METHODS: We designed a framework to infer health condition collections (HCCs)
      based on the similarity of their clinical workflows, according to electronic
      medical record (EMR) utilization. We evaluated the framework with data from over
      16,500 inpatient stays from Northwestern Memorial Hospital in Chicago, Illinois.
      The plausibility of the inferred HCCs for bundled care was assessed through an
      online survey of a panel of five experts, whose responses were analyzed via an
      analysis of variance (ANOVA) at a 95% confidence level. We further assessed the
      face validity of the HCCs using evidence in the published literature. RESULTS:
      The framework inferred four HCCs, indicative of (1) fetal abnormalities, (2) late
      pregnancies, (3) prostate problems, and (4) chronic diseases, with congestive
      heart failure featuring prominently. Each HCC was substantiated with evidence in
      the literature and was deemed plausible for bundled care by the experts at a
      statistically significant level. CONCLUSIONS: The findings suggest that an
      automated EMR data-driven framework conducted can provide a basis for discovering
      bundled care opportunities. Still, translating such findings into actual care
      management will require further refinement, implementation, and evaluation.

PMID- 29174995
TI  - Evaluation of the new restandardized 25-hydroxyvitamin D assay on the iSYS
      platform.
AB  - BACKGROUND: 25-hydroxyvitamin D [25(OH)D] is the most reliable biomarker of
      vitamin D status, but until now 25(OH)D assays have suffered from inter
      laboratory and inter-assay discrepancies. In the setting of the international
      Vitamin D Standardization Program, Immunodiagnostic Systems (IDS) recently
      reformulated and restandardized the 25(OH)D immunoassay available on the
      automated iSYS platform. In the present study, we evaluated this new generation
      of the 25(OH)D immunoassay (IS-2500). METHODS: Repeatability and within
      laboratory imprecision were verified according to the Clinical and Laboratory
      Standards Institute EP15-A3. Results from the sera of 63 patients were compared
      with those obtained with the previous iSYS method (IS-2700S) using Passing-Bablok
      and Bland-Altman analysis. The prevalence and bias-adjusted kappa (PABAK)
      coefficient was calculated to assess the agreement of vitamin D status provided
      by the two iSYS immunoassays. Fourteen Vitamin D External Quality Assessment
      Scheme (DEQAS) samples were used to evaluate inaccuracy. RESULTS: Using the EP15
      A3 protocol, repeatability and within-laboratory imprecision obtained with the
      new iSYS method were lower than 6% and 8%, respectively. These results are
      consistent with the manufacturer's claims. In more adverse conditions (50
      measurements over 15days with multiple calibrations), the within-laboratory
      imprecision was 14.8% (39nmol/L) and 7.7% (155nmol/L). 25(OH)D concentrations
      measured with the new assay showed a strong correlation with those provided by
      the previous version (r=0.969, p<0.0001). The Passing-Bablok regression equation
      was as follows: new assay=1.079 x (previous assay) - 3.6nmol/L. The PABAK
      coefficient of 0.810 reflected almost perfect agreement between the two
      immunoassays to classify patients according to their vitamin D status (85.7% of
      agreement). Using DEQAS samples, the mean inaccuracy bias was lower than 5% when
      the new iSYS method was compared with LC-MS/MS methods and the NIST reference
      measurement procedure. CONCLUSION: The new generation of the iSYS immunoassay
      evaluated in this study meets requirements for routinely measuring 25(OH)D levels
      in clinical laboratories.

PMID- 29174996
TI  - Infants Born with Down Syndrome: Burden of Disease in the Early Neonatal Period.
AB  - OBJECTIVE: To evaluate the incidence of direct admission of infants with Down
      syndrome to the postnatal ward (well newborn nursery) vs the neonatal intensive
      care unit (NICU), and to describe the incidence of congenital heart disease (CHD)
      and pulmonary hypertension (PH). STUDY DESIGN: This retrospective cohort study of
      Down syndrome used the maternal/infant database (2011-2016) at the Rotunda
      Hospital in Dublin, Ireland. Admission location, early neonatal morbidities,
      outcomes, and duration of stay were evaluated and regression analyses were
      conducted to identify risk factors associated with morbidity and mortality.
      RESULTS: Of the 121 infants with Down syndrome, 54 (45%) were initially admitted
      to the postnatal ward, but 38 (70%) were later admitted to the NICU. Low oxygen
      saturation profile was the most common cause for the initial and subsequent
      admission to the NICU. Sixty-six percent of the infants (80/121) had CHD, 34%
      (41/121) had PH, and 6% died. Risk factors independently associated with primary
      NICU admission included antenatal diagnosis of Down syndrome, presence of CHD,
      PH, and the need for ventilation. CONCLUSIONS: Infants with Down syndrome
      initially admitted to the postnatal ward have a high likelihood of requiring NICU
      admission. Overall, high rates of neonatal morbidity were noted, including rates
      of PH that were higher than previously reported. Proper screening of all infants
      with Down syndrome for CHD and PH is recommended to facilitate timely diagnoses
      and potentially shorten the duration of the hospital stay.

PMID- 29174997
TI  - Is It Necessary to Heat and Humidify Respiratory Gases for Resuscitation in
      Preterm Infants?

PMID- 29174998
TI  - Psychosis and Clinical Outcomes in Alzheimer Disease: A Longitudinal Study.
AB  - OBJECTIVE: Psychotic symptoms are a common feature in Alzheimer disease (AD),
      occurring in approximately 40% of patients. These symptoms are associated with
      worse clinical outcomes. Comparatively little research, however, has
      distinguished delusions and hallucinations, which may have distinct clinical,
      neuropathological, and genetic correlates. To address this, the current study
      examined the clinical outcomes associated with delusions and hallucinations in
      AD. DESIGN: Three-year observational study. SETTING: Nine memory clinics in
      Australia. PARTICIPANTS: A total of 445 patients with AD. MEASUREMENTS: Measures
      of neuropsychiatric symptoms, dementia severity, cognition, function, caregiver
      burden, and medication use were completed annually for 3 years with additional
      assessments at 3 months and 6 months in the first year. Mortality data were
      obtained from state registries approximately 5 years after the study. RESULTS: Of
      445 patients, 102 (22.9%) developed only delusions, 39 (8.8%) developed only
      hallucinations, and 84 (18.9%) developed both symptoms. Delusions and
      hallucinations were both associated with greater dementia severity, poorer
      cognition and function, higher levels of other neuropsychiatric symptoms, and
      greater caregiver burden. The presence of both symptoms was associated with worse
      outcomes than only one of these symptoms. Delusions, both by themselves and in
      combination with hallucinations, predicted institutionalization. Antipsychotic
      medication use predicted mortality. CONCLUSIONS: Delusions and hallucinations
      independently and in combination are associated with poor clinical outcomes. The
      findings highlight the challenges managing these patients, particularly given the
      high levels of caregiver burden associated with psychotic symptoms and the likely
      mortality arising from antipsychotic medication.

PMID- 29174999
TI  - Effect of upper body plyometric training on physical performance in healthy
      individuals: A systematic review.
AB  - OBJECTIVE: To determine the impact of upper body plyometric training (UBPT) on
      physical performance parameters such as strength, ball throwing speed, ball throw
      distance and power in healthy individuals. METHODS: PubMed, Scopus, ResearchGate
      and ERIC databases were searched up to August 2017. Selection of articles was
      done if they described the outcomes of an upper body plyometric exercise
      intervention; included measures of strength, ball throwing speed, ball throw
      distance, or power; included healthy individuals; used a randomized control
      trial; and had full text available in English language. The exclusion criteria
      were unpublished research work and clubbing of UBPT with some other type(s) of
      training apart from routine sports training. PEDro scale was used to rate the
      quality of studies eligible for this review. RESULTS: Initially 264 records were
      identified and out of them only 11 articles met the eligibility criteria and were
      selected (PEDro score = 4 to 6). Though large to very small effects observed in
      improving ball throwing velocity, ball throwing distance, power and strength of
      upper limb muscles after UBPT, the results should be implemented with caution.
      CONCLUSION: Inconclusive results obtained preclude any strong conclusion
      regarding the efficacy of UBPT on physical performance in healthy individuals.

PMID- 29175001
TI  - Contribution of the swine model in the study of human sexually transmitted
      infections.
AB  - The pig has garnered more and more interest as a model animal to study various
      conditions in humans. The growing success of the pig as an experimental animal
      model is explained by its similarities with humans in terms of anatomy, genetics,
      immunology, and physiology, by their manageable behavior and size, and by the
      general public acceptance of using pigs for experimental purposes. In addition,
      the immunological toolbox of pigs has grown substantially in the last decade.
      This development led to a boost in the use of pigs as a preclinical model for
      various human infections including sexually transmitted diseases (STIs) like
      Chlamydia trachomatis. In the current review, we discuss the use of animal models
      for biomedical research on the major human STIs. We summarize results obtained in
      the most common animal models and focus on the contributions of the pig model
      towards the understanding of pathogenesis and the host immune response. In
      addition, we present the main features of the porcine model that are particularly
      relevant for the study of pathogens affecting human female and male genital
      tracts. We also inform on the technological advancements in the porcine toolbox
      to facilitate new discoveries in this biologically important animal model. There
      is a continued need for improvements in animal modeling for biomedical research
      inclusive STI research. With all its advantages and the highly improved toolbox,
      the porcine model can play a crucial role in STI research and open the door to
      new exciting discoveries.

PMID- 29175002
TI  - Complete genome sequence of Granulosicoccus antarcticus type strain IMCC3135T, a
      marine gammaproteobacterium with a putative dimethylsulfoniopropionate
      demethylase gene.
AB  - Granulosicoccus, the only genus of the family Granulosicoccaceae, occupies a
      distinct phylogenetic position within the order Chromatiales of the
      Gammaproteobacteria. The genus has been found in various marine regions,
      especially associated with diverse marine macroalgae. No genomes have been
      reported for the genus Granulosicoccus thus far, hampering studies on physiology
      and lifestyles of this genus. Here we report the complete genome sequence of
      strain IMCC3135T, the type strain of Granulosicoccus antarcticus isolated from
      Antarctic coastal seawater. The genome was 7.78Mbp long and harbored many genes
      involved in sulfur metabolism. In particular, a gene for
      dimethylsulfoniopropionate (DMSP) demethylase was found in the genome, rendering
      strain IMCC3135T one of the few marine gammaproteobacteria equipped with the
      potential for DMSP demethylation.

PMID- 29175004
TI  - Editorial.

PMID- 29175003
TI  - Transcranial direct current stimulation (tDCS) prevents chronic stress-induced
      hyperalgesia in rats.
AB  - BACKGROUND: Chronic stress (CS) is associated with a decrease in pain threshold
      caused by the changes in neural pain circuits. It can be associated to
      glucocorticoid imbalance with alterations in neural circuitry. Inhibition of
      stress-induced pain-related neural changes by using techniques that safely induce
      neuroplasticity such as transcranial direct current stimulation (tDCS) may
      prevent hyperalgesia triggered by CS. OBJECTIVE: This study aimed to verify the
      effect of tDCS performed prior to CS exposure on nociceptive response. METHODS:
      Thirty-two rats were distributed in the following groups: control; stress; sham
      tDCS + stress; and tDCS + stress. Bicephalic active tDCS was performed for 8
      consecutive days before the CS exposure. The pain threshold was evaluated using a
      hot plate and tail flick latency (TFL) tests. RESULTS: The tDCS exposure
      increased the pain threshold on stressed rats. CONCLUSION: The data obtained
      indicate that the treatment with bicephalic active tDCS before chronic stress
      exposure prevents stress-induced hyperalgesia.

PMID- 29175005
TI  - Physician perceptions of integrating advanced practice pharmacists into practice.
AB  - OBJECTIVES: Barriers have prevented full integration of advanced practice
      pharmacists (APPs) into collaborative practice in some areas despite evidence
      describing their value. APPs in North Carolina can be recognized as Clinical
      Pharmacist Practitioners (CPPs) under a collaborative practice agreement and
      provide comprehensive medication management under physician supervision. This
      study describes the perceptions of physicians regarding the barriers and benefits
      of integrating CPPs into interprofessional teams and compares physician and CPP
      perceptions. METHODS: This prospective descriptive study surveyed CPP supervising
      physicians in North Carolina. The questionnaire consisted of 17 multiple-choice
      and free-response questions. Questions included demographics, perceived benefits
      and challenges of incorporating CPPs into health care teams, and services
      provided by CPPs. Findings were compared with previously published data that
      assessed CPP perceptions about the same topics to gain insight into common
      perspectives of team members. RESULTS: Fifty-six physicians (23.1%) responded,
      identifying enhanced clinical outcomes (87.5%), access to drug knowledge (58.9%),
      and creation of a multidisciplinary model for learners (57.1%) as the top
      benefits of working with CPPs. Primary barriers included limited reimbursement
      (60.7%) and billing difficulties (51.8%). More CPPs acknowledged provider
      acceptance as a barrier (25.9% vs. 3.6%; P = 0.001). Twelve physicians (21.4%)
      and no CPPs identified space as a barrier. CONCLUSION: Physicians identified
      enhanced clinical outcomes, access to drug knowledge, and creation of a
      multidisciplinary model for learners as the top benefits of incorporating CPPs
      into teams, and billing difficulties and limited reimbursement were the primary
      barriers. These findings were similar to the perceptions of CPPs, with exceptions
      being that physicians were more concerned about space limitations and CPPs noted
      that provider acceptance may be difficult. These findings may provide guidance to
      providers desiring to establish collaborative practice.

PMID- 29175006
TI  - Predicted cumulative dose to firefighters and the offsite public from natural and
      anthropogenic radionuclides in smoke from wildland fires at the Savannah River
      Site, South Carolina USA.
AB  - The contaminated ground surface at Savannah River Site (SRS) is a result of the
      decades of work that has been performed maintaining the country's nuclear
      stockpile and performing research and development on nuclear materials. The
      volatilization of radionuclides during wildfire results in airborne particles
      that are dispersed within the smoke plume and may result in doses to downwind
      firefighters and the public. To better understand the risk that these smoke
      plumes present, we have characterized four regions at SRS in terms of their fuel
      characteristics and radiological contamination on the ground. Combined with
      general meteorological conditions describing typical and extreme burn conditions,
      we have simulated potential fires in these regions and predicted the potential
      radiological dose that could be received by firefighting personnel and the public
      surrounding the SRS. In all cases, the predicted cumulative dose was a small
      percent of the US Department of Energy regulatory limit (0.25 mSv). These
      predictions were conservative and assumed that firefighters would be exposed for
      the duration of their shift and the public would be exposed for the entire day
      over the duration of the burn. Realistically, firefighters routinely rotate off
      the firefront during their shift and the public would likely remain indoors much
      of the day. However, we show that even under worst-case conditions the regulatory
      limits are not exceeded. We can infer that the risks associated with wildfires
      would not be expected to cause cumulative doses above the level of concern to
      either responding personnel or the offsite public.

PMID- 29175007
TI  - High Radon Areas and lung cancer prevalence: Evidence from Ireland.
AB  - This paper examined the relationship between radon risk and lung cancer
      prevalence using a novel dataset combining spatially-coded survey data with a
      radon risk map. A logit model was employed to test for significant associations
      between a high risk of indoor radon and lung cancer prevalence using data on 5590
      people aged 50+ from The Irish Longitudinal Study on Ageing (TILDA) and radon
      risk data from Ireland's Environmental Protection Agency (EPA). The use of data
      at the individual level allowed a wide range of potentially confounding factors
      (such as smoking) to be included. Results indicate that those who lived in an
      area in which 10%-20% of households were above the national reference level (200
      Bq/m3) were 2.9-3.1 times more likely to report a lung cancer diagnosis relative
      to those who lived in areas in which less than 1% of households were above the
      national reference level.

PMID- 29175000
TI  - Cyclic nucleotide signaling changes associated with normal aging and age-related
      diseases of the brain.
AB  - Deficits in brain function that are associated with aging and age-related
      diseases benefit very little from currently available therapies, suggesting a
      better understanding of the underlying molecular mechanisms is needed to develop
      improved drugs. Here, we review the literature to test the hypothesis that a
      break down in cyclic nucleotide signaling at the level of synthesis, execution,
      and/or degradation may contribute to these deficits. A number of findings have
      been reported in both the human and animal model literature that point to brain
      region-specific changes in Galphas (a.k.a. Galphas or Gsalpha), adenylyl cyclase,
      3',5'-adenosine monophosphate (cAMP) levels, protein kinase A (PKA), cAMP
      response element binding protein (CREB), exchange protein activated by cAMP
      (Epac), hyperpolarization-activated cyclic nucleotide-gated ion channels (HCNs),
      atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), soluble and
      particulate guanylyl cyclase, 3',5'-guanosine monophosphate (cGMP), protein
      kinase G (PKG) and phosphodiesterases (PDEs). Among the most reproducible
      findings are 1) elevated circulating ANP and BNP levels being associated with
      cognitive dysfunction or dementia independent of cardiovascular effects, 2)
      reduced basal and/or NMDA-stimulated cGMP levels in brain with aging or
      Alzheimer's disease (AD), 3) reduced adenylyl cyclase activity in hippocampus and
      specific cortical regions with aging or AD, 4) reduced expression/activity of PKA
      in temporal cortex and hippocampus with AD, 5) reduced phosphorylation of CREB in
      hippocampus with aging or AD, 6) reduced expression/activity of the PDE4 family
      in brain with aging, 7) reduced expression of PDE10A in the striatum with
      Huntington's disease (HD) or Parkinson's disease, and 8) beneficial effects of
      select PDE inhibitors, particularly PDE10 inhibitors in HD models and PDE4 and
      PDE5 inhibitors in aging and AD models. Although these findings generally point
      to a reduction in cyclic nucleotide signaling being associated with aging and age
      related diseases, there are exceptions. In particular, there is evidence for
      increased cAMP signaling specifically in aged prefrontal cortex, AD cerebral
      vessels, and PD hippocampus. Thus, if cyclic nucleotide signaling is going to be
      targeted effectively for therapeutic gain, it will have to be manipulated in a
      brain region-specific manner.

PMID- 29175008
TI  - Recall Urticaria in Adalimumab Hypersensitivity.

PMID- 29175009
TI  - Treatment with mTOR inhibitors after liver transplantation enables a sustained
      increase in regulatory T-cells while preserving their suppressive capacity.
AB  - BACKGROUND: The mammalian targets of rapamycin (mTOR) inhibitors (sirolimus [SRL]
      and everolimus [EVR]) are used after transplantation for their immunosuppressive
      activity. Regulatory T-cells (Tregs) play a crucial role in immune tolerance.
      mTOR inhibitors appear to preserve Tregs, unlike Tacrolimus (Tac). AIM: The aim
      of this study was to evaluate the number and function of Tregs in liver
      transplant recipients before and after conversion from Tac to mTOR inhibitors.
      METHODS: Fifteen patients with stable graft function where converted to SRL (n=5)
      or EVR (n=10). Tregs (CD4+ CD25+ FoxP3+ CD127low) number and activity were
      analysed prospectively in blood cells using flow cytometry, and functional assay.
      RESULTS: Patients of both groups displayed a sustained rise in Treg levels after
      introduction of mTOR inhibitors (Treg levels at 3 months: 6.45+/-0.38% of CD4 T
      cells, vs. baseline level of 3.61+/-0.37%, P<0.001; mean fold increase 2.04+/
      0.73). In SRL group, 3-month Treg levels were 6.01+/-0.53 vs. 3.79+/-0.39;
      P=0.037, while in EVR group they were 6.63+/-0.67 vs. 3.54+/-0.51; P=0.001. By
      contrast, no statistical change was observed in an unconverted Tac control group.
      Tregs also preserved their functional ability to suppress activated T-cells.
      CONCLUSION: These results suggest that mTOR inhibitors induce a significant
      increase in Tregs while maintaining suppressive activity after LT.

PMID- 29175011
TI  - Effects of moroxydine hydrochloride and ribavirin on the cellular growth and
      immune responses by inhibition of GCRV proliferation.
AB  - Moroxydine hydrochloride (Mor) and ribavirin (Rib) are known for their multi
      antiviral activities against DNA and RNA viruses but little information is
      available about the pharmacological impact in aquaculture. The present study was
      undertaken to investigate the response of host cells to antiviral compounds
      during the anti-GCRV treatment. The scanning electron microscope results showed
      that Ctenopharyngodon idella kidney (CIK) cells have a higher death rate at 72h
      post virus infection. At the concentration of 40MUgmL-1, Mor and Rib had a
      significant protective effect on virus-infected cells. Moreover, the gene
      expressions of vp5, vp6 and NS66 were significantly inhibited by treatment with
      Mor or Rib, especially gene expression of the vp5. For the immunoregulatory
      action, no distinct induction of the expression of immune genes was observed
      after the addition of Mor and Rib to the virus-free cells. However, the compounds
      significantly decreased the virus-induced gene overexpression of Myd88, Mx1, IL
      1beta, IL-8, I-IFN and TNFalpha in CIK cells. Moreover, Mor and Rib significantly
      inhibited the immune genes upregulation which was induced by GCRV in kidney,
      liver, muscle and gill of grass carp, despite greater partial gene expressions
      were detected than the virus-free control group. Besides, Mor and Rib blocked
      cell cycle changes, cytopathic effects, cellular death and virus proliferation in
      CIK cells thereby maintaining normal morphological structure. Overall, Mor and
      Rib as antiviral compounds are effective for the control of GCRV replication and
      the indirectly regulation of cellular immune response.

PMID- 29175010
TI  - Regulation of B cell fate, survival, and function by mitochondria and autophagy.
AB  - B cells are responsible for protective antibody production after differentiation
      into antibody-secreting cells during humoral immune responses. From early B cell
      development in the bone marrow, to their maturation in the periphery, activation
      in the germinal center, and differentiation into plasma cells or memory B cells,
      B cells display ever-changing functions and properties. Autophagy and
      mitochondria play important roles in B cell development, activation, and
      differentiation to accommodate the phenotypic and environmental changes
      encountered over the lifetime of the cell. Among their many functions,
      mitochondria and autophagy generate energy, mediate cell survival, and
      produce/eliminate reactive oxygen species that can serve as signal molecules to
      regulate differentiation. As B cells mature and differentiate into plasma or
      memory cells, both autophagic and mitochondrial functions undergo significant
      changes. In this review, we aim to provide an overview of the role of the
      autophagosome and mitochondria in regulating B cell fate, survival, and function.
      Moreover, we will discuss the interplay between these two highly metabolic
      organelles during B cell development, maturation, and differentiation.

PMID- 29175012
TI  - Osteogenic differentiation of equine adipose tissue derived mesenchymal stem
      cells using CaCl2.
AB  - Adipose tissue derived mesenchymal stem cells (ASCs) may be used to cure bone
      defects after osteogenic differentiation. In this study we tried to optimize
      osteogenic differentiation for equine ASCs using various concentrations of CaCl2
      in comparison to the standard osteogenic protocol. ASCs were isolated from
      subcutaneous adipose tissue from mixed breed horses. The osteogenic induction
      protocols were (1) the standard osteogenic medium (OM) composed of dexamethasone,
      ascorbic acid and beta-glycerol phosphate; (2) CaCl2 based protocol composed of
      3, 5 and 7.5mM CaCl2. Differentiation and proliferation were evaluated at 7, 10,
      14 and 21days post-differentiation induction using the alizarin red staining
      (ARS) detecting matrix calcification. Semi-quantification of cell protein
      content, ARS and alkaline phosphatase activity (ALP) were performed using an
      ELISA reader. Quantification of the transcription level for the common osteogenic
      markers alkaline phosphatase (ALP) and Osteopontin (OP) was performed using RT
      qPCR. In the presence of CaCl2, a concentration dependent effect on the
      osteogenic differentiation capacity was evident by the ARS evaluation and OP gene
      expression. We provide evidence that 5 and 7mM CaCl2 enhance the osteogenic
      differentiation compared to the OM protocol. Although, there was a clear
      commitment of ASCs to the osteogenic fate in the presence of 5 and 7mM CaCl2,
      cell proliferation was increased compared to OM. We report that an optimized
      CaCl2 protocol reliably influences ASCs osteogenesis while conserving the
      proliferation capacity. Thus, using these protocols provide a platform for using
      ASCs as a cell source in bone tissue engineering.

PMID- 29175013
TI  - The PB2-K627E mutation attenuates H3N2 swine influenza virus in cultured cells
      and in mice.
AB  - PB2-627K is an important amino acid that determines the virulence of some
      influenza A viruses. However, it has not been experimentally investigated in the
      H3N2 swine influenza virus. To explore the potential role of PB2-K627E
      substitution in H3N2 swine influenza virus, the growth properties and
      pathogenicity between H3N2 swine influenza virus and its PB2-K627E mutant were
      compared. For the first time, our results showed that PB2-K627E mutation
      attenuates H3N2 swine influenza virus in mammalian cells and in mice, suggesting
      that PB2-627K is required for viral replication and pathogenicity of H3N2 swine
      influenza virus.

PMID- 29175014
TI  - Influence of sedation on onset and quality of euthanasia in sheep.
AB  - The purpose of this study was to determine if dexmedetomidine administered IV
      prior to euthanasia in sheep affected the speed or quality of euthanasia. Twenty
      clinically healthy Dorset-cross adult ewes between 1 and 3years of age were
      enrolled in a randomized blinded experimental trial. The subjects were randomly
      assigned to receive dexmedetomidine 5MUg/kg IV or an equivalent volume of saline.
      Five minutes later, euthanasia was accomplished with a pentobarbital/phenytoin
      overdose given IV. The time to apnea, asystole, cessation of audible heartbeat,
      and absence of corneal reflex were recorded by two blinded investigators. If any
      muscle spasms, contractions, vocalization, and/or dysrhythmias were noted, the
      time was recorded and type of ECG abnormality was described. An overall score of
      the euthanasia event was assigned using a numeric rating scale (NRS) after the
      animal was declared dead. The time to loss of corneal reflex was significantly
      longer in sheep given dexmedetomidine compared with those who received saline
      (P=0.03). Although vocalization was observed only in some animals premedicated
      with dexmedetomidine, no significance was found for this event and no other
      significant differences between groups were noted. Dexmedetomidine at 5MUg/kg IV
      5min prior to injection of pentobarbital/phenytoin for euthanasia did not
      substantially affect the progress of euthanasia. Dexmedetomidine may be given to
      sedate sheep prior to euthanasia without concern for it adversely affecting the
      progress of euthanasia, however vocalization may occur.

PMID- 29175015
TI  - Intestinal colonisation with extended-spectrum cephalosporin-resistant
      Enterobacteriaceae in different populations in Switzerland: prevalence, risk
      factors and molecular features.

PMID- 29175016
TI  - Optimised Helicobacter pylori antibiotic susceptibility profile using gold
      standard method.

PMID- 29175017
TI  - Inhibitory effects of (+)-spectaline and iso-6-spectaline from Senna spectabilis
      on the growth and ultrastructure of human-infective species Trypanosoma brucei
      rhodesiense bloodstream form.
AB  - In our ongoing work searching for new trypanocidal lead compounds from Malaysian
      plants, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline
      (2) were isolated from the leaves of Senna spectabilis (sin. Cassia spectabilis).
      Analysis of the 1H and 13C NMR spectra showed that 1 and 2 presented analytical
      and spectroscopic data in full agreement with those published in the literature.
      All compounds were screened in vitro against Trypanosoma brucei rhodesiense in
      comparison to the standard drug pentamidine. Compound 1 and 2 inhibited growth of
      T. b. rhodesiense with an IC50 value of 0.41 +/- 0.01 MUM and 0.71 +/- 0.01 MUM,
      without toxic effect on L6 cells with associated a selectivity index of 134.92
      and 123.74, respectively. These data show that piperidine alkaloids constitute a
      class of natural products that feature a broad spectrum of biological activities,
      and are potential templates for the development of new trypanocidal drugs. To our
      knowledge, the compounds are being reported for the first time to have inhibitory
      effects on T. b. rhodesiense. The ultrastructural alterations in the trypanosome
      induced by 1 and 2, leading to programmed cell death were characterized using
      electron microscopy. These alterations include wrinkling of the trypanosome
      surface, formation of autophagic vacuoles, disorganization of kinetoplast, and
      swelling of the mitochondria. These findings evidence a possible autophagic cell
      death.

PMID- 29175018
TI  - Understanding serine proteases implications on Leishmania spp lifecycle.
AB  - Serine proteases have significant functions over a broad range of relevant
      biological processes to the Leishmania spp lifecycle. Data gathered here present
      an update on the Leishmania spp serine proteases and the status of these enzymes
      as part of the parasite degradome. The serine protease genes (n = 26 to 28) in
      Leishmania spp, which encode proteins with a wide range of molecular masses (35
      kDa-115 kDa), are described along with their degrees of chromosomal and allelic
      synteny. Amid 17 putative Leishmania spp serine proteases, only ~18% were
      experimentally demonstrated, as: signal peptidases that remove the signal peptide
      from secretory pre-proteins, maturases of other proteins and with metacaspase
      like activity. These enzymes include those of clans SB, SC and SF. Classical
      inhibitors of serine proteases are used as tools for the characterization and
      investigation of Leishmania spp. Endogenous serine protease inhibitors, which are
      ecotin-like, can act modulating host actions. However, crude or synthetic based
      natural serine protease inhibitors, such as potato tuber extract, Stichodactyla
      helianthus protease inhibitor I, fukugetin and epoxy-alpha-lapachone act on
      parasitic serine proteases and are promising leishmanicidal agents. The
      functional interrelationship between serine proteases and other Leishmania spp
      proteins demonstrate essential functions of these enzymes in parasite physiology
      and therefore their value as targets for leishmaniasis treatment.

PMID- 29175019
TI  - Long-term outcome and quality of life after initial and repeat resection of
      colorectal liver metastasis: A retrospective analysis.
AB  - BACKGROUND: Repeat hepatectomy is a widely accepted treatment for patients with
      recurrent colorectal liver metastasis (CRLM). The aim of this study was to
      compare initial and repeat hepatic resection concerning overall survival,
      prognostic factors and postoperative quality of life. METHODS: Data on patients
      who underwent initial or repeat hepatic resection for CRLM between 2010 and 2016
      were prospectively collected and retrospectively evaluated. Follow-up data, EORTC
      QLQ-C30 and QLQ-LMC21 questionnaire results for quality of life (QoL) evaluation
      were analyzed. RESULTS: 160 patients at a median age of 62.8 +/- 11.8 years were
      analyzed. 122 were initially resected and 38 underwent a repeat hepatic
      resection. Disease-free survival (DSF) was superior in the initial resection
      group (p < 0.001), while there was no difference in overall survival (OS) (p =
      0.288). BMI >30 (p = 0.012), extrahepatic tumor manifestation (p = 0.037), >1
      CRLM manifestation (p = 0.009), and perioperative chemotherapy (p = 0.006) in the
      initial resection group and primary left colon tumor (p = 0.001) in the repeat
      resection group were identified as prognostic factors in multivariate Cox
      regression analysis. EORTC QLQ-LMC-21 module symptom score displayed an increased
      occurrence of a dry mouth in the initial hepatectomy group (p = 0.003). EORTC QLQ
      C30 general functioning and symptom scores showed no difference. CONCLUSION:
      Repeat hepatic resection for CRLM is as effective as primary surgical treatment
      in terms of OS and QoL. Patients should be selected carefully concerning
      prognostic factors as DFS is decreased after repeat hepatic resection.

PMID- 29175020
TI  - Sentinel lymph node biopsy validation for large tumors.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) remains under discussion for large
      size tumors. The aim of this work has been to study the false negative rate (FNR)
      of SLNB for large tumors and predictive factors of false negative (FN). MATERIALS
      AND METHODS: A study of a multicentric cohort, involved patients presenting N0
      breast cancer with a SLNB eventually completed by complementary axillary lymph
      node dissection (cALND). The main criteria were the FNR and the predictive
      factors of FN. RESULTS: 12.415 patients were included: 748 with tumors >=30 mm,
      1101 with tumors >20 and < 30 mm and 10.566 with tumors <=20 mm, with a cALND
      respectively for 501 patients (67%), 523 (62.1%) and 2775 (26.3%). The FNR were
      respectively: 3.05% (IC95%: 1.3-4.8) for tumors >=30 mm*, 3.5% (1.8-5.2) for
      tumors >20 and < 30 mm*, 1.8% (1-2.4) for tumors <=20 mm (p < 0.05) (*Not
      significant). At multivariate analysis, SN number harvested <=2 (OR:2.0, p =
      0.023) and tumor size >20 and < 30 mm (OR:2.07, p = 0.017) were significant
      predictive factors of FN, without significant value for tumor size >=30 mm
      (OR:1.83, p = 0.073). CONCLUSION: The FNR of SLNB was not higher amongst large
      size tumors compared to tumors of a smaller size. These results support the
      validation of SNLB for tumors up to 50 mm.

PMID- 29175022
TI  - Biology and treatment of myeloma related bone disease.
AB  - Myeloma bone disease (MBD) is the most common complication of multiple myeloma
      (MM), resulting in skeleton-related events (SREs) such as severe bone pain,
      pathologic fractures, vertebral collapse, hypercalcemia, and spinal cord
      compression that cause significant morbidity and mortality. It is due to an
      increased activity of osteoclasts coupled to the suppressed bone formation by
      osteoblasts. Novel molecules and pathways that are implicated in osteoclast
      activation and osteoblast inhibition have recently been described, including the
      receptor activator of nuclear factor-kB ligand/osteoprotegerin pathway, activin-A
      and the wingless-type signaling inhibitors, dickkopf-1 (DKK-1) and sclerostin.
      These molecules interfere with tumor growth and survival, providing possible
      targets for the development of novel drugs for the management of lytic disease in
      myeloma but also for the treatment of MM itself. Currently, bisphosphonates are
      the mainstay of the treatment of myeloma bone disease although several novel
      agents such as denosumab and sotatercept appear promising. This review focuses on
      recent advances in MBD pathophysiology and treatment, in addition to the
      established therapeutic guidelines.

PMID- 29175023
TI  - Reliability of measurements for sub-painful and painful perception on artificial
      electrical stimulations.
AB  - Artificial electrical stimulation is a common type of stimulus to induce sub
      painful and painful sensation in clinical or neuroscience experiments. The
      Numerical Rating Scale (NRS) is often used to evaluate subjective perception due
      to external stimulations. Yet the relationship between the intensity levels of
      electrical stimulations and self-perception has seldom been examined. The aim of
      the study was to obtain evidence on the reliability and accuracy of sub-painful
      and painful perceptions of healthy participants using the NRS under different
      levels of electrical stimulus. A total of 72 pain-free healthy volunteers
      (female=44) were recruited. In the first experiment, each participant was given
      different levels of a non-nociceptive or nociceptive electrical stimulus and then
      asked to give a perception rating based on an 11-point NRS. In the second
      experiment, each participant was asked to memorize 5 levels of sub-nociceptive or
      nociceptive stimuli and to recognize the level of stimulus given each time. For
      the NRS rating task, intraclass coefficients (ICCs) reached satisfactory level
      for sub-nociceptive (0.85<ICC<0.93) and nociceptive stimulation (0.90<ICC<0.96).
      The ICCs were the highest for the weakest sub-nociceptive and nociceptive
      stimuli. For the stimulus recognition task, accuracy was also found to be highest
      for the weakest sub-nociceptive stimulus (kappa=0.67) and lowest for the
      strongest nociceptive stimulus (kappa=0.34). The results suggest that, with
      adequate training, NRS can be a reliable measurement tool for both sub-painful
      and painful rating due to electrical stimulation.

PMID- 29175021
TI  - PTEN-Dependent Stabilization of MTSS1 Inhibits Metastatic Phenotype in Pancreatic
      Ductal Adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) presents at metastatic stage in over 50%
      of patients. With a survival rate of just 2.7% for patients presenting with
      distant disease, it is imperative to uncover novel mechanisms capable of
      suppressing metastasis in PDAC. Previously, we reported that the loss of
      metastasis suppressor protein 1 (MTSS1) in PDAC cells results in significant
      increase in cellular migration and invasion. Conversely, we also found that
      overexpressing MTSS1 in metastatic PDAC cell lines corresponds with not only
      decreased metastatic phenotype, but also greater overall survival. While it is
      known that MTSS1 is downregulated in late-stage PDAC, the mechanism behind that
      loss has not yet been elucidated. Here, we build off our previous findings to
      present a novel regulatory mechanism for the stabilization of MTSS1 via the tumor
      suppressor protein phosphatase and tensin homolog (PTEN). We show that PTEN loss
      in PDAC cells results in a decrease in MTSS1 expression and increased metastatic
      potential. Additionally, we demonstrate that PTEN forms a complex with MTSS1 in
      order to stabilize and protect it from proteasomal degradation. Finally, we show
      that the inflammatory tumor microenvironment, which makes up over 90% of PDAC
      tumor bulk, is capable of downregulating PTEN expression through secretion of
      miRNA-23b, potentially uncovering a novel extrinsic mechanism of MTSS1
      regulation. Collectively, these data offer new insight into the role and
      regulation of MTSS1in suppressing tumor cell invasion and migration and help shed
      light as to what molecular mechanisms could be leading to early cell
      dissemination in PDAC.

PMID- 29175024
TI  - Y-type urethral duplication with rectal implantation of the urethra: Which is the
      best approach?
AB  - INTRODUCTION: Y-type urethral duplication describes the condition in which a
      functional urethra is implanted in the rectum, and there is also a dysplastic
      topic urethra which produces mostly urinary dribbling. These patients are at risk
      of urinary tract complications and UTI. We aimed to present the surgical steps of
      a case treated by ASTRA approach in which we separated the urethra from the
      rectum and created a perineal urethrostomy. MATERIAL AND METHODS: We treated a 5
      month-old boy with Y-type (IIA-2) urethral duplication, in whom the orthotopic
      urethra was patent just in the penile segment. The patient had urinary flow per
      anus and minimal dribbling through the orthotopic urethra. We performed a
      combined cystoscopy with retrograde urethrogram and managed to catheterize the
      dysplastic urethra with a guide-wire that showed ectopic implantation in the
      prostatic urethra, below the bladder neck. We performed an ASTRA procedure to
      separate the urethra from the rectum. The urethral stump was further mobilized to
      the perineum and anastomosed to a perineal skin flap to create a stoma and
      minimize the risk of stricture. RESULTS: The patient was followed at 2 month
      intervals, and at 6 months follow-up had an excellent outcome. CONCLUSION: The
      ASTRA approach proved to be an excellent alternative for Y-type urethral
      duplication with functional urethra implanted in the rectum. We believe that
      further efforts to reconstruct the urethra should be avoided, with a better and
      simpler option being to create a definitive perineal urethrostomy.

PMID- 29175025
TI  - Witnessed overdoses and naloxone use among visitors to Rikers Island jails
      trained in overdose rescue.
AB  - With the opioid overdose mortality rates rising nationally, The New York City
      Department of Health and Mental Hygiene (NYC DOHMH) has worked to expand overdose
      rescue training (ORT) and naloxone distribution. This study sought to determine
      rates of overdose witnessing and naloxone use among overdose rescue-trained
      visitors to the NYC jails on Rikers Island. We conducted a six-month prospective
      study of visitors to NYC jails on Rikers Island who received ORT. We collected
      baseline characteristics of study participants, characteristics of overdose
      events, and responses to witnessed overdose events, including whether the victim
      was the incarcerated individual the participant was visiting on the day of
      training. Bivariate analyses compared baseline characteristics of participants
      who witnessed overdoses to those who did not, and of participants who used
      naloxone to those who did not. Overall, we enrolled 283 participants visiting
      NYC's Rikers Island jails into the study. Six months after enrollment, we reached
      226 participants for follow-up by phone. 40 participants witnessed 70 overdose
      events, and 28 participants reported using naloxone. Of the 70 overdose events,
      three victims were the incarcerated individuals visited on the day of training;
      nine additional victims were recently released from jail and/or prison. Visitors
      to persons incarcerated at Rikers Island witness overdose events and are able to
      perform overdose rescues with naloxone. This intervention reaches a population
      that includes not only those recently released, but also other people who
      experienced overdose.

PMID- 29175026
TI  - Measuring E-cigarette use, dependence, and perceptions: Important principles and
      considerations to advance tobacco regulatory science.

PMID- 29175028
TI  - 17beta-estradiol locally increases phasic dopamine release in the dorsal
      striatum.
AB  - Studies using in vivo microdialysis have shown that 17beta-estradiol (E2)
      increases dopamine (DA) transmission in the dorsal striatum. Both systemic
      administration of E2 and local infusion into the dorsal striatum rapidly enhance
      amphetamine-induced DA release. However, it is not known to what degree these
      effects reflect tonic and/or phasic DA release. It was hypothesized that E2 acts
      directly within the DS to rapidly increase phasic DA transmission. In urethane
      anesthetized (1.5mL/kg) female rats, we used fast-scan cyclic voltammetry to
      study the effects of E2 on phasic, electrically-evoked release of DA in the
      dorsal striatum. Rats were ovariectomized and implanted with a silastic tube
      containing 5% E2 in cholesterol, previously shown to mimic low physiological
      serum concentrations of~20-25pg/mL. DA release was evoked every 1min by
      delivering biphasic electrical stimulation in the substantia nigra. Local
      infusions of E2 (244.8pg/MUl) into the dorsal striatum increased the amplitude of
      the electrically evoked DA transients. Behaviorally significant stimuli and
      events trigger phasic release of DA. The present findings predict that E2 would
      boost such signaling in behaving subjects.

PMID- 29175027
TI  - Measuring perceptions related to e-cigarettes: Important principles and next
      steps to enhance study validity.
AB  - Measuring perceptions associated with e-cigarette use can provide valuable
      information to help explain why youth and adults initiate and continue to use e
      cigarettes. However, given the complexity of e-cigarette devices and their
      continuing evolution, measures of perceptions of this product have varied
      greatly. Our goal, as members of the working group on e-cigarette measurement
      within the Tobacco Centers of Regulatory Science (TCORS) network, is to provide
      guidance to researchers developing surveys concerning e-cigarette perceptions. We
      surveyed the 14 TCORS sites and received and reviewed 371 e-cigarette perception
      items from seven sites. We categorized the items based on types of perceptions
      asked, and identified measurement approaches that could enhance data validity and
      approaches that researchers may consider avoiding. The committee provides
      suggestions in four areas: (1) perceptions of benefits, (2) harm perceptions, (3)
      addiction perceptions, and (4) perceptions of social norms. Across these 4 areas,
      the most appropriate way to assess e-cigarette perceptions depends largely on
      study aims. The type and number of items used to examine e-cigarette perceptions
      will also vary depending on respondents' e-cigarette experience (i.e., user vs.
      non-user), level of experience (e.g., experimental vs. established), type of e
      cigarette device (e.g., cig-a-like, mod), and age. Continuous formative work is
      critical to adequately capture perceptions in response to the rapidly changing e
      cigarette landscape. Most important, it is imperative to consider the unique
      perceptual aspects of e-cigarettes, building on the conventional cigarette
      literature as appropriate, but not relying on existing conventional cigarette
      perception items without adjustment.

PMID- 29175029
TI  - Depletion of D3 dopamine receptor affects methamphetamine-induced expression
      patterns of Pde4b and Atf3.
AB  - The role of the D3 dopamine receptor (D3R) and the specific molecular mechanisms
      underlying the regulation of D3R via the cAMP signaling pathway in
      methamphetamine (METH) addiction are still unclear. Here, we measured changes in
      Pde4b and Atf3 in the cAMP signaling pathway of dopaminergic system components,
      including the nucleus accumbens (NAc), caudate putamen (CPu) and hippocampus
      (Hip), in D3R knockout mice(D3R-/-) 1h and 24h after METH-induced behavioral
      sensitization. We found that knocking out D3R attenuated METH-induced behavioral
      sensitization, and Pde4b and Atf3 exhibited different expression patterns in
      brain regions in response to METH. Knocking out D3R suppressed the METH-induced
      increase in Pde4b in the Hip of mice 24h after the final METH injection and
      augmented the METH-induced increase in Atf3 in the CPu of mice 1h after the final
      METH injection. Our study suggests that D3R knockout controls METH-induced
      behavioral sensitization via regulation of Pde4b and Atf3 in different brain
      regions. Furthermore, the responses of Pde4b and Atf3 to METH exposure depend on
      the specific region of the brain involved.

PMID- 29175030
TI  - Changes of the brain activities after chronic restraint stress in rats: A study
      based on 18F-FDG PET.
AB  - As a prevalent disease all over the world, changed functional activities and/or
      structures in many brain regions have been found in depression. In this study, 5
      week chronic restraint stress (CRS) was performed to establish depression rat
      models, and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was
      used to detect brain functional activities. Our study found that CRS induced
      depressive behaviors and increased the expression of serum IL-6. After exposure
      to CRS, rats showed decreased glucose metabolism in the whole-brain and brain
      regions including left medial prefrontal and auditory cortices; right amygdala,
      cingulate cortex, olfactory and AcbCore/Shell; bilateral caudate putamen, dorsal
      hippocampi, insular and entorhinal cortices. Expression of serum IL-6 and glucose
      metabolism in most of the above brain regions were significantly correlated with
      the severity of some CRS-induced depressive behaviors. In conclusion, the
      increased peripheral inflammatory response and decreased brain functional
      activities might be the important pathogenesis of experimental depression induced
      by CRS, and could reflect the severity of depression to some extent.

PMID- 29175031
TI  - Dopamine neuron loss by selective deletion of autophagy-related gene 5 is not
      exacerbated by MPTP toxicity in midbrain.
AB  - Parkinson's disease (PD) is a progressive neurological disease, one of the
      pathological characteristics is a gradual loss of midbrain dopaminergic (mDA)
      neurons in the substantia nigra pars compacta (SNpc). In animals, PD-like
      symptoms can be induced by genetic mutations or by neurotoxins such as 1-methyl-4
      phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). It has been reported that deletion
      of autophagy-related gene 5 (Atg5) in the brain can disrupt neural function and
      is accompanied by the accumulation of cytoplasmic inclusions. However, the exact
      role of autophagy in PD etiology has not fully been asserted. In this study, we
      used tyrosine hydroxylase (TH)-Cre mice to generate conditional knockouts (CKO)
      with the specific deletion of Atg5 in mDA neurons, and found that adult Atg5 CKO
      mice contained ubiquitin- and p62-positive inclusions and fewer TH-positive mDA
      neurons compared with wild-type controls. Interestingly, MPTP-induced loss of mDA
      neurons was not observed in Atg5 CKO mice. Thus, Atg5-associated autophagy is
      required for the survival of mDA neurons, and may be involved in MPTP-induced
      neuronal degeneration.

PMID- 29175032
TI  - Convergent and divergent functional connectivity patterns in patients with long
      term left-sided and right-sided deafness.
AB  - Cortical reorganization may be induced in long-term single-sided deafness (SD);
      however, the influence of the deafness side on the functional changes remains
      poorly understood. Here, we investigated whole-brain functional connectivity
      patterns in long-term SD patients. The normalized voxel-based functional
      connectivity strength (FCS) was determined using resting-state fMRI (rs-fMRI) in
      17 left-sided deafness (LD) patients, 21 right-sided deafness (RD) patients and
      21 healthy controls (HCs). Relative to the HCs, both the LD and RD patients
      exhibited a reduction in the FCS in the ipsilateral visual cortex. However,
      compared to that in the HCs, a significantly higher FCS was observed in some
      regions in the salience and default-mode networks in the RD patients, but this
      FCS alternation pattern was not observed in the LD patients. A direct comparison
      of the two patient groups revealed a significantly increased FCS in the
      supplemental motor area in the LD group. Altogether, the long-term SD groups with
      LD and RD exhibited convergent and divergent functional connectivity patterns in
      whole-brain networks, providing promising evidence that the functional changes in
      long-term SD are highly deafness-side-dependent.

PMID- 29175033
TI  - Evidence of Varroa-mediated deformed wing virus spillover in Hawaii.
AB  - Varroa destructor, a parasitic mite of honey bees, is also a vector for viral
      diseases. The mite displays high host specificity and requires access to colonies
      of Apis spp. to complete its lifecycle. In contrast, the Deformed Wing Virus
      (DWV), one of the many viruses transmitted by V. destructor, appears to have a
      much broader host range. Previous studies have detected DWV in a variety of
      insect groups that are not directly parasitized by the mite. In this study, we
      take advantage of the discrete distribution of the Varroa mite in the Hawaiian
      archipelago to compare DWV prevalence on non-Apis flower visitors, and test
      whether Varroa presence is linked to a "viral spillover". We selected two islands
      with different viral landscapes: Oahu, where V. destructor has been present since
      2007, and Maui, where the mite is absent. We sampled individuals of Apis
      mellifera, Ceratina smaragdula, Polistes aurifer, and Polistes exclamens, to
      assess and compare the DWV prevalence in the Hymenoptera community of the two
      islands. The results indicated that, as expected, honey bee colonies on Oahu have
      much higher incidence of DWV compared to Maui. Correspondingly, DWV was detected
      on the Non-Apis Hymenoptera collected from Oahu, but was absent in the species
      examined on Maui. The study sites selected shared a similar geography, climate,
      and insect fauna, but differed in the presence of the Varroa mite, suggesting an
      indirect, but significant, increase on DWV prevalence in the Hymenoptera
      community on mite-infected islands.

PMID- 29175034
TI  - Characterisation of blaOXA-538, a new variant of blaOXA-48, in Shewanella
      xiamenensis isolated from river water in Algeria.
AB  - OBJECTIVES: In this study, the presence of carbapenemase genes in Shewanella
      xiamenensis strains isolated from river water in Bejaia, Algeria, was
      investigated. METHODS: Four isolates of S. xiamenensis were isolated from water
      from Soummam River. The isolates were identified by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) and
      sequencing of the 16S rRNA and gyrB genes. Isolates were subjected to
      antimicrobial susceptibility testing. Carbapenemase production was screened using
      phenotypic tests. PCR and sequencing were used to identify carbapenemase genes in
      the isolates. The genetic context of the blaOXA-48-like gene was investigated by
      sequencing the whole genome of strain AS58. RESULTS: All four S. xiamenensis
      strains harboured blaOXA-48-like genes. They exhibited different resistance
      patterns and had imipenem minimum inhibitory concentrations (MICs) of >=0.5mg/L.
      Sequencing of blaOXA-48-like genes from the S. xiamenensis isolates showed that
      two strains harboured blaOXA-181, one strain harboured blaOXA-199 and one strain
      exhibited a new variant of the blaOXA-48-like gene, named blaOXA-538. This new
      variant shared 98% nucleotide identity with blaOXA-162, with three amino acid
      changes (G201A, A213G and I219F). Conjugation assays with Escherichia coli J53
      recipient were performed but no transconjugants were obtained. Analysis of the
      genome of AS58 Touati strain confirmed the chromosomal location of the blaOXA-538
      gene. CONCLUSION: This study showed that environmental water holds a diversity of
      S. xiamenensis strains harbouring blaOXA-48-like genes and may play an important
      role in the dissemination and spread of these genes from the environment to
      humans.

PMID- 29175035
TI  - Characterization of a Pseudoxanthoma elasticum-like patient with coagulation
      deficiency, cutaneous calcinosis and GGCX compound heterozygosity.

PMID- 29175036
TI  - Evaluation of postoperative patient satisfaction after covering the nasal dorsum
      with upper lateral cartilage: "upper lateral closing".
AB  - INTRODUCTION: Following nasal hump removal during septorhinoplasty, the middle
      vault should be reconstructed to avoid functional and esthetic problems. Middle
      vault reconstruction, however, may result in widening of the middle vault and may
      need a camouflage graft to cover dorsal irregularities. OBJECTIVE: To present the
      results of reconstructing the middle vault with a technique that covers the nasal
      dorsum with upper lateral cartilage, from the viewpoint of patient satisfaction.
      METHODS: Retrospective study of patients who underwent septorhinoplasty that
      included nasal dorsum closure with upper lateral cartilage from December 1, 2014
      to January 31, 2016. Those with postoperative follow-up of less than 3 months
      were excluded. The final study group included 39 patients. The same surgeon
      performed all septorhinoplasties. The dorsum was closed using an "upper lateral
      closing" technique that approximated upper lateral cartilages to each other over
      the septum. Postoperative patient satisfaction was determined using a visual
      analog scale and the rhinoplasty outcomes evaluation questionnaire. The
      questionnaire evaluates patient esthetic and functional satisfaction with the
      operated nose. High scores indicate improved esthetic results. RESULTS: No dorsal
      irregularities were seen at postoperative follow-up evaluation of the patients.
      For esthetic nasal appearance, the median visual analogue scale scores was 86%,
      and the mean for the questionnaire was 77.03%. CONCLUSION: The natural dome
      shaped anatomy of the nasal dorsum was achieved by approximating the upper
      lateral cartilages to each other. Closing the dorsum with this technique also
      covers any dorsal irregularities and results in a smooth dorsum. Patients
      expressed satisfaction with the esthetic and functional aspects of the smooth,
      attractive nasal dorsum.

PMID- 29175037
TI  - Results from a multicenter registry of heparin-bonded expanded
      polytetrafluoroethylene graft for above-the-knee femoropopliteal bypass.
AB  - OBJECTIVE: The aim of the study was to retrospectively analyze early and follow
      up results of above-the-knee femoropopliteal bypasses (AKb) performed with a
      bioactive heparin-bonded expanded polytetrafluoroethylene (HB-ePTFE) graft in
      patients with peripheral arterial obstructive disease in a multicentric
      retrospective registry involving seven Italian vascular centers. METHODS: During
      a 14-year period ending in March 2016, an HB-ePTFE graft was used in 1401
      interventions performed for peripheral arterial obstructive disease.
      Comorbidities, risk factors, and follow-up outcomes were collected in a
      multicenter registry with a dedicated database. A post hoc analysis of the
      database was performed to identify 364 (25.9%) patients who underwent AKb. Early
      (intraoperative and <30 days) results were analyzed in terms of death,
      thrombosis, amputations, reinterventions, and the occurrence of major local and
      systemic complications. Follow-up results were analyzed by life-table analysis
      (Kaplan-Meier test) in terms of primary and secondary graft patency, assisted
      primary patency, limb preservation, and amputation-free survival. The analysis of
      follow-up results was stopped in December 2016. RESULTS: In 61 (16.7%) patients,
      AKb was performed after the failure of a previous ipsilateral revascularization.
      Critical limb ischemia was present in 164 (45%) cases; the remaining patients had
      life-limiting intermittent claudication. Perioperative mortality occurred in
      three (0.8%) patients: in the hospital (n = 2) due to acute myocardial infarction
      and after discharge (n = 1) due to fatal arrhythmia. Early thromboses occurred in
      six (1.6%) patients; all these patients had primary AKb for critical limb
      ischemia. The cumulative rate of perioperative amputations was 0.5% (2 cases),
      whereas the cumulative rate of early reinterventions was 3% (11 cases). Median
      duration of follow-up was 28 months (range, 1-168 months); the median cumulative
      follow-up index for survival was 0.75 (range, 0.05-1). Estimated survival at 5
      years was 75.3% (standard error [SE], 0.03). Estimated 5-year primary patency was
      64% (SE, 0.04); the corresponding figure in terms of assisted primary patency was
      65% (SE, 0.035). Secondary patency rate at 5 years was 74.5% (SE, 0.03). The rate
      of limb preservation at 5 years was 95% (SE, 0.02); the corresponding figure in
      terms of amputation-free survival was 74% (SE, 0.04). CONCLUSIONS: In an era of
      endovascular enthusiasm, with conflicting results for the treatment of long or
      complex lesions of the superficial femoral artery, AKb with the use of HB-ePTFE
      graft remains an effective option, with low rate of perioperative complications
      and satisfactory long-term results.

PMID- 29175038
TI  - Renin-angiotensin system blockade does not attenuate abdominal aortic aneurysm
      growth, rupture rate, or perioperative mortality after elective repair.
AB  - OBJECTIVE: The objective of this study was to summarize the literature regarding
      the effects of renin-angiotensin system blockade (RASB) using angiotensin
      converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) on
      human abdominal aortic aneurysm (AAA) growth, rupture, and perioperative
      mortality. METHODS: We conducted a systematic review in accordance with Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Our review
      protocol was registered at the International Prospective Register of Systematic
      Reviews (CRD42016054082). We searched the Cochrane Central Register of Controlled
      Trials database, MEDLINE, and Embase from inception to 2017 for studies examining
      the effects of ACEi or ARB treatment on AAA growth, rupture, or perioperative
      mortality. Review, abstraction, and quality assessment were conducted in
      duplicate, and a third author resolved discrepancies. We assessed study quality
      using the Cochrane and Newcastle-Ottawa scales. We used random-effects models to
      calculate pooled mean differences and odds ratios (ORs) with 95% confidence
      intervals (CIs). Heterogeneity was quantified using the I2 statistic. RESULTS:
      Our search yielded 525 articles. One randomized and seven observational studies
      involving 35,448 patients were included. Inter-rater agreement was excellent
      (kappa = 0.78), and risk of bias was low to moderate. All studies investigated
      ACEis, three studies investigated ARBs, and two studies included a composite RASB
      group consisting of ACEi or ARB users. Five studies assessed AAA growth, two
      assessed rupture rate, and one reported 30-day mortality after elective open
      repair. There was no difference in AAA growth rate between RASB and control (mean
      difference, 0.03 mm/y; 95% CI, -0.40 to 0.46; P = .88; I2 = 60%). No protective
      effect of RASB (OR, 0.92; 95% CI, 0.72, 1.16; P = .47; I2 = 90%) was demonstrated
      for AAA rupture. Finally, RASB increased 30-day mortality in patients undergoing
      elective open AAA repair (OR, 5; 95% CI, 1.4, 27) according to a single well
      adjusted study. CONCLUSIONS: RASB does not appear to affect AAA growth and
      rupture rate but increases elective perioperative mortality. The small number of
      heterogeneous, retrospective studies and limited long-term follow-up preclude a
      definitive dismissal of RASB as pharmacotherapy for AAA. Prospective, long-term
      data are needed to clarify the effect of RASB on AAA growth, rupture, and
      perioperative mortality.

PMID- 29175039
TI  - Clostridium difficile Infection Among Individuals With Inflammatory Bowel
      Disease.

PMID- 29175040
TI  - Reply.

PMID- 29175041
TI  - Reply.

PMID- 29175042
TI  - Gallbladder Cancer and Aflatoxin: Do We Have Sufficient Evidence?

PMID- 29175043
TI  - An Extremely Rare Cause of Dysphagia.

PMID- 29175044
TI  - An Unusual Cause of a Retroperitoneal Fluid Collection.

PMID- 29175045
TI  - Prevalence of Helicobacter pylori Infection in Asia: Remembrance of Things Past?

PMID- 29175046
TI  - Serum anion gap predicts lactate poorly, but may be used to identify sepsis
      patients at risk for death: A cohort study.
AB  - PURPOSE: (1) To test whether serum bicarbonate or anion gap can be used to
      predict elevated lactate or mortality in emergency department (ED) patients with
      sepsis, and (2) to define thresholds that may predict elevated lactate and
      mortality. METHODS: Retrospective diagnostic-validation study of adults with
      sepsis treated in a 60,000-visit Midwestern university ED (2010-2015). In the
      derivation sample, 8 experts selected thresholds based on objective measures to
      optimize clinical utility. Test performance was reported using likelihood ratios
      (LR +/-) in the validation cohort. RESULTS: We included 4159 patients. Anion gap
      predicted lactate>2 better than bicarbonate [ROC AUC 0.680 vs. 0.609], and anion
      gap predicted lactate>4 better than lactate>2 [ROC AUC 0.816 vs. 0.680]. In the
      validation cohort, anion gap >=20mEq/L had LR+ for lactate>2 of 3.670 (2.630
      5.122), lactate>4 of 7.019 (5.310-9.278), and mortality of 2.768 (1.922-3.986).
      Anion gap predicted mortality similar to lactate>2 [LR+ 2.768 vs. LR+ 2.09; LR-
      0.823 vs. 0.447]. CONCLUSIONS: Anion gap and serum bicarbonate poorly predict
      changes in lactate and mortality. In resource-limited settings where lactate is
      unavailable, anion gap >=20mEq/L may be used to further risk-stratify patients
      for ongoing sepsis care, but lactate remains a preferred biomarker.

PMID- 29175047
TI  - Hemorrhagic shock drives glycocalyx, barrier and organ dysfunction early after
      polytrauma.
AB  - Polytrauma (PT) is frequently associated with hemorrhagic shock (HS), which
      increases morbidity and mortality. Although various aspects of HS have been
      addressed in PT patients, the impact of an additional HS is largely unknown
      regarding the development of multiple organ dysfunction associated with disturbed
      glycocalyx and barrier function early after trauma. A prospective, longitudinal,
      mono-centered, observational study enrolling severely injured patients (Injury
      Severity Score, ISS=38.1+/-2.6) served for an in-depth analysis of blood (drawn
      on days 0, 1, 2, 3 and 5) and clinical data (up to 21days) of 30 patients who
      were then stratified into PT with and without HS. HS significantly enhanced signs
      of acute organ injury, assessed by increased serum concentrations of novel damage
      markers. Moreover, indicators of glycocalyx and tight-junction dysfunction were
      found in PT patients all of which were significantly enhanced in co-presence of
      HS. These markers revealed multiple significant correlations with specific
      barrier, fluid-balance, coagulation, inflammation, and clinical-outcome
      parameters. Strikingly, mucosa fragments, which affected clotting, could be
      detected in serum after PT/HS. The results point to HS as a main driver for
      glycocalyx and barrier breakdown and suggest novel tools for the monitoring of
      organ dysfunction in the early course after PT.

PMID- 29175048
TI  - Predictive accuracy of medical transport information for in-hospital mortality.

PMID- 29175049
TI  - Managing sepsis.

PMID- 29175050
TI  - Vacuolar protein sorting 13C is a novel lipid droplet protein that inhibits
      lipolysis in brown adipocytes.
AB  - OBJECTIVE: Brown adipose tissue (BAT) thermogenesis depends on the mobilization
      and oxidation of fatty acids from intracellular lipid droplets (LD) within brown
      adipocytes (BAs); however, the identity and function of LD proteins that control
      BAT lipolysis remain incomplete. Proteomic analysis of mouse BAT subcellular
      fractions identified vacuolar protein sorting 13C (VPS13C) as a novel LD protein.
      The aim of this work was to investigate the role of VPS13C on BA LDs. METHODS:
      Biochemical fractionation and high resolution confocal and immuno-transmission
      electron microscopy (TEM) were used to determine the subcellular distribution of
      VPS13C in mouse BAT, white adipose tissue, and BA cell culture. Lentivirus
      delivered shRNA was used to determine the role of VPS13C in regulating lipolysis
      and gene expression in cultured BA cells. RESULTS: We found that VPS13C is highly
      expressed in mouse BAT where it is targeted to multilocular LDs in a subspherical
      subdomain. In inguinal white adipocytes, VPS13C was mainly observed on small LDs
      and beta3-adrenergic stimulation increased VPS13C in this depot. Silencing of
      VPS13C in cultured BAs decreased LD size and triglyceride content, increased
      basal free fatty acid release, augmented the expression of thermogenic genes, and
      enhanced the lipolytic potency and efficacy of isoproterenol. Mechanistically, we
      found that BA lipolysis required activation of adipose tissue triglyceride lipase
      (ATGL) and that loss of VPS13C greatly increased the association of ATGL to LDs.
      CONCLUSIONS: VPS13C is present on BA LDs where is targeted to a distinct
      subdomain. VPS13C limits the access of ATGL to LD and loss of VPS13C elevates
      lipolysis and promotes oxidative gene expression.

PMID- 29175051
TI  - Fatty acid oxidation is required for active and quiescent brown adipose tissue
      maintenance and thermogenic programing.
AB  - OBJECTIVE: To determine the role of fatty acid oxidation on the cellular,
      molecular, and physiologic response of brown adipose tissue to disparate
      paradigms of chronic thermogenic stimulation. METHODS: Mice with an adipose
      specific loss of Carnitine Palmitoyltransferase 2 (Cpt2A-/-), that lack
      mitochondrial long chain fatty acid beta-oxidation, were subjected to
      environmental and pharmacologic interventions known to promote thermogenic
      programming in adipose tissue. RESULTS: Chronic administration of beta3
      adrenergic (CL-316243) or thyroid hormone (GC-1) agonists induced a loss of BAT
      morphology and UCP1 expression in Cpt2A-/- mice. Fatty acid oxidation was also
      required for the browning of white adipose tissue (WAT) and the induction of UCP1
      in WAT. In contrast, chronic cold (15  degrees C) stimulation induced UCP1 and
      thermogenic programming in both control and Cpt2A-/- adipose tissue albeit to a
      lesser extent in Cpt2A-/- mice. However, thermoneutral housing also induced the
      loss of UCP1 and BAT morphology in Cpt2A-/- mice. Therefore, adipose fatty acid
      oxidation is required for both the acute agonist-induced activation of BAT and
      the maintenance of quiescent BAT. Consistent with this data, Cpt2A-/- BAT
      exhibited increased macrophage infiltration, inflammation and fibrosis
      irrespective of BAT activation. Finally, obese Cpt2A-/- mice housed at
      thermoneutrality exhibited a loss of interscapular BAT and were refractory to
      beta3-adrenergic-induced energy expenditure and weight loss. CONCLUSION:
      Mitochondrial long chain fatty acid beta-oxidation is critical for the
      maintenance of the brown adipocyte phenotype both during times of activation and
      quiescence.

PMID- 29175052
TI  - Changing temporal trends in non-AIDS cancer mortality among people diagnosed with
      AIDS: San Francisco, California, 1996-2013.
AB  - BACKGROUND: Antiretroviral therapy (ART) has reduced AIDS-defining cancer (ADC)
      mortality, but its effect on non-AIDS-defining cancer (NADC) mortality is
      unclear. To help inform cancer prevention and screening, we evaluated trends in
      NADC mortality among people with AIDS (PWA) in the ART era. METHODS: This
      retrospective cohort study analyzed AIDS surveillance data, including causes of
      death from death certificates, for PWA in San Francisco who died in 1996-2013.
      Proportional mortality ratios (PMRs), and year, age, race, sex-adjusted
      standardized mortality ratios (SMRs) were calculated for 1996-1999, 2000-2005,
      and 2006-2013, corresponding to advances in ART. RESULTS: The study included 5822
      deceased PWA of whom 90% were male and 68% were aged 35-54 at time of death. Over
      time, the PMRs significantly decreased for ADCs (2.6%, 1.4%, 1.2%) and increased
      for NADCs (4.3%, 7.0%, 12.3%). For all years combined (1996-2013) and compared to
      the California population, significantly elevated SMRs were observed for these
      cancers: all NADCs combined (2.1), anal (58.4), Hodgkin lymphoma (10.5), liver
      (5.2), lung/larynx (3.0), rectal (5.2), and tongue (4.7). Over time, the SMRs for
      liver cancer (SMR 19.8, 11.2, 5.0) significantly decreased while the SMRs
      remained significantly elevated over population levels for anal (SMR 123, 48.2,
      45.5), liver (SMR 19.8, 11.2, 5.0), and lung/larynx cancer (SMR 5.3, 4.7, 3.6).
      CONCLUSION: A decline in ADC PMRs and increase in NADC PMRs represent a shift in
      the cancer burden, likely due to ART use. Moreover, given their elevated SMRs,
      anal, liver, and lung/larynx cancer remain targets for improved cancer
      prevention, screening, and treatment.

PMID- 29175053
TI  - The evolutionary conservation of the bidirectional activity of the NWC gene
      promoter in jawed vertebrates and the domestication of the RAG transposon.
AB  - The RAG-1 and RAG-2 genes form a recombinase complex that is indispensable for
      V(D)J recombination, which generates the diversity of immunoglobulins and T-cell
      receptors. It is widely accepted that the presence of RAGs in the genomes of
      jawed vertebrates and other lineages is a result of the horizontal transfer of a
      mobile genetic element. While a substantial amount of evidence has been gathered
      that clarifies the nature of the RAG transposon, far less attention has been paid
      to the genomic site of its integration in various host organisms. In all genomes
      of the jawed vertebrates that have been studied to date, the RAG genes are
      located in close proximity to the NWC gene. We have previously shown that the
      promoter of the murine NWC genes exhibits a bidirectional activity, which may
      have facilitated the integration and survival of the RAG transposon in the host
      genome. In this study, we characterise the promoters of the NWC homologues that
      are present in the representatives of other jawed vertebrates (H. sapiens, X.
      tropicalis and D. rerio). We show that the features that are characteristic for
      promoters as the hosts of a successful transposon integration (in terms of the
      arrangement, bidirectional and constitutive activity and the involvement of the
      Zfp143 transcription factor in the promoter regulation) are evolutionarily
      conserved, which indicates that the presence of RAG genes in jawed vertebrates is
      a direct result of a successful transposon integration into the NWC locus.

PMID- 29175054
TI  - Phenotypic and functional characterization of porcine bone marrow monocyte
      subsets.
AB  - Monocytes comprise several subsets with distinct phenotypes and functional
      capacities. Based on CD163 expression, two major monocyte subsets can be
      discriminated in the porcine bone marrow. The CD163+ cells expressed higher
      levels of SLA-DR, Siglec-1, CD11R1 and CD16 when compared to CD163- monocytes,
      whereas no remarkable differences were observed in the expression of other
      markers analyzed. Gene expression analysis showed differential expression of
      several chemokine receptor and TLR genes. Both subsets phagocytosed microspheres
      with similar efficiency. However, CD163- cells tended to produce higher levels of
      ROS in response to PMA, whereas CD163+ cells were more efficient in endocytosing
      and processing antigens (DQ-OVA). CD163- monocytes produced higher levels of TNF
      alpha and IL-10 than CD163+ cells when stimulated with LPS or Imiquimod. Both
      subsets produced similar amounts of IL-8 in response to LPS; however, CD163+
      cells produced more IL-8 after Imiquimod stimulation. Whether these subsets
      represent different developmental stages, and how are they related remain to be
      investigated.

PMID- 29175055
TI  - Cortical morphometric changes after spinal cord injury.
AB  - Neuroimaging studies suggest that spinal cord injury (SCI) may lead to
      significant anatomical alterations in the human sensorimotor system. In
      particular, voxel-based morphometry (VBM) of cortical volume has revealed a
      significant gray and white matter atrophy bilaterally in the primary sensory
      cortex (S1). By contrast, some structural studies failed to detect changes in
      gray matter volume (GMV) in the primary motor cortex (M1) following SCI, whereas
      others have reported a substantial decrease of GMV also in M1. In addition to
      direct degeneration of the sensorimotor cortex, SCI can also lead to atrophy of
      the non-sensorimotor cortex, such as anterior cingulate cortex, insular cortex,
      middle frontal gyrus and supplementary motor area. These findings suggest that
      SCI can cause remote atrophy of brain gray matter in the salient network.
      Furthermore, pain-related remodelling may occur in SCI. In fact, structural
      changes in SCI are also related to the presence and degree of below-level pain.
      We performed a systematic review of the neuroimaging studies showing morphometric
      cortical changes and subsequent functional reorganization in humans with SCI.
      Literature search was conducted using PubMed and Embase. We identified 12
      articles matching the inclusion criteria and 195 patients were included in these
      studies. The wide range of disease duration, rehabilitation training, drug
      intervention, and different research methodology, especially the identification
      of region of interest and the statistical approach to correct for multiple
      comparisons, may have contributed to some inconsistencies between the reviewed
      studies. Nevertheless, neuroimaging biomarkers can assess the extent of neural
      damage, elucidate the mechanisms of neural repair, and predict clinical outcome.
      A better understanding of the structural and functional changes that occur at
      cortical level following SCI may be useful in tracking potential treatment
      induced changes and identifying potential therapeutic targets, thus developing
      evidence-based rehabilitation therapies.

PMID- 29175056
TI  - Evaluation of cardiac energetics by non-invasive 31P magnetic resonance
      spectroscopy.
AB  - Alterations in myocardial energy metabolism have been implicated in the
      pathophysiology of cardiac diseases such as heart failure and diabetic
      cardiomyopathy. 31P magnetic resonance spectroscopy (MRS) is a powerful tool to
      investigate cardiac energetics non-invasively in vivo, by detecting phosphorus
      (31P)-containing metabolites involved in energy supply and buffering. In this
      article, we review the historical development of cardiac 31P MRS, the readouts
      used to assess cardiac energetics from 31P MRS, and how 31P MRS studies have
      contributed to the understanding of cardiac energy metabolism in heart failure
      and diabetes. 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- 29175058
TI  - Instituting Ultrasound-Guided FNA for Thyroid Nodules into a General Surgery
      Residency Program: What We Learned.
AB  - BACKGROUND: Evaluation of a thyroid nodule is a common referral seen by surgeons
      and frequently requires ultrasound-guided fine needle aspiration (US-guided FNA).
      While surgical residents may have sufficient exposure to thyroid surgery, many
      lack exposure to office-based procedures, such as US-guided FNA. General surgery
      residents should be provided with knowledge and practical skills in the
      application of diagnostic and interventional neck ultrasound to manage the common
      workup of a thyroid nodule. METHODS: This study sought to instruct and measure
      surgical residents' performance in thyroid US-guided FNA and evaluate their views
      regarding instituting such a formal curriculum. Twelve (n = 12) senior residents
      completed a written pretest and questionnaire, then watched an instructional
      video and practiced a simulated thyroid US-guided FNA on our created model. Then
      residents were evaluated while performing actual thyroid US-guided FNAs on
      patients in our clinic. Residents then completed the same written exam and
      questionnaire for objective measure. RESULTS: Eight of the chief residents (62%)
      felt "not comfortable" with the procedure on the pre-course survey; this was
      reduced to 0% on the post-course survey. Moderate comfort level increased from
      15% to 50% and extreme comfort increased from 0% to 8%. From the 11 residents who
      completed the pre- and post-test exam, 82% (n = 9) significantly improved their
      score through the curriculum (pre-test: 40.9 vs. post-test: 61.8; p = 0.05).
      CONCLUSION: With focused instruction, residents are able to learn ultrasound
      guided thyroid biopsy with improvement in subjective confidence level and
      objective measures. Resident feedback was positive and emphasized the importance
      of such training in surgical residency curriculum.

PMID- 29175057
TI  - Simvastatin blocks soluble SSAO/VAP-1 release in experimental models of cerebral
      ischemia: Possible benefits for stroke-induced inflammation control.
AB  - Beyond cholesterol reduction, statins mediate their beneficial effects on stroke
      patients through pleiotropic actions. They have shown anti-inflammatory
      properties by a number of different mechanisms, including the inhibition of NF
      kappaB transcriptional activity and the consequent increase and release of
      adhesion molecules. We have studied simvastatin's effects on the vascular enzyme
      semicarbazide-sensitive amine oxidase/vascular adhesion protein 1 (SSAO/VAP-1),
      which is involved in stroke-mediated brain injury. SSAO/VAP-1 has leukocyte
      binding capacity and mediates the expression of other adhesion proteins through
      signaling molecules generated by its catalytic activity. Our results indicate
      that soluble SSAO/VAP-1 is released into the bloodstream after an ischemic
      stimulus, in parallel with an increase in E-selectin and VCAM-1 and correlating
      with infarct volume. Simvastatin blocks soluble SSAO/VAP-1 release and prevents E
      selectin and VCAM-1 overexpression as well. Simvastatin also effectively blocks
      SSAO/VAP-1-mediated leukocyte adhesion, although it is not an enzymatic inhibitor
      of SSAO in vitro. In addition, simvastatin-induced changes in adhesion molecules
      are greater in human brain endothelial cell cultures expressing SSAO/VAP-1,
      compared to those not expressing it, indicating some synergic effect with
      SSAO/VAP-1. We think that part of the beneficial effect of simvastatin in stroke
      is mediated by the attenuation of the SSAO/VAP-1-dependent inflammatory response.

PMID- 29175059
TI  - Relationship between temperament and fatness in 11-year-old children and 17-year
      old adolescents from Wroclaw, Poland.
AB  - Childhood obesity is increasing globally, and Poland is no exception. Studies
      indicate that relationship between obesity and psychological well-being is a
      complex issue and this needs further research. The objective of the present cross
      sectional study was to analyze the relationship between some temperament
      components and fatness among children in two developmental periods, approximately
      before and after adolescence. Participants included 122 children aged 11 years
      (57 boys and 65 girls), and 153 adolescents aged 17 years (64 boys and 89 girls)
      from 6 primary and 4 secondary schools in Wroclaw, Poland. Height, weight,
      triceps-, subscapular and abdominal skinfold thicknesses were measured.
      Temperament was assessed by a questionnaire of Buss and Plomin (1984) in two
      versions: EAS-C for children completed by parents and EAS-D for youth and adults.
      Physical activity (PAL) was also assessed by a questionnaire. Mean, median and
      standard deviation (SD) were calculated and Student's t tests were performed to
      test for significance of differences between groups. Chi squared (chi2) statistic
      was used to test the significance of differences in frequencies. Analyses of
      covariance (ANCOVA) were performed to show the effect of the social -
      psychological factors on fatness. Controlling for socioeconomic status and
      physical activity level, activity, as a component of temperament had a
      significant effect on body fatness. The only component of temperament, which
      significantly influenced level of fatness in girls, was emotionality. These
      relationships differed according to sex and the two age groups concerned.

PMID- 29175060
TI  - Evaluation of the contribution of D9S1120 to anthropological studies in Native
      American populations.
AB  - The D9S1120 locus exhibits a population-specific allele of 9 repeats (9RA) in all
      Native American and two Siberian populations currently studied, but it is absent
      in other worldwide populations. Although this feature has been used in
      anthropological genetic studies, its impact on the evaluation of the structure
      and genetic relations among Native American populations has been scarcely
      assessed. Consequently, the aim of this study was to evaluate the anthropological
      impact of D9S1120 when it was added to STR population datasets in Mexican Native
      American groups. We analyzed D9S1120 by PCR and capillary electrophoresis (CE) in
      1117 unrelated individuals from 13 native groups from the north and west of
      Mexico. Additional worldwide populations previously studied with D9S1120 and/or
      15 autosomal STRs (Identifier kit) were included for interpopulation analyses. We
      report statistical results of forensic importance for D9S1120. On average, the
      modal alleles were the Native American-specific allele 9RA (0.3254) and 16
      (0.3362). Genetic distances between Native American and worldwide populations
      were estimated. When D9S1120 was included in the 15 STR population dataset, we
      observed improvements for admixture estimation in Mestizo populations and for
      representing congruent genetic relationships in dendrograms. Analysis of
      molecular variance (AMOVA) based on D9S1120 confirms that most of the genetic
      variability in the Mexican population is attributable to their Native American
      backgrounds, and allows the detection of significant intercontinental
      differentiation attributed to the exclusive presence of 9RA in America. Our
      findings demonstrate the contribution of D9S1120 to a better understanding of the
      genetic relationships and structure among Mexican Native groups.

PMID- 29175061
TI  - Sex-specific reliability and multidimensional stability of responses to tests
      assessing neuromuscular function.
AB  - The objective of this study was to estimate sex-specific effects in the test
      retest cross-reliability of peripheral and central changes in nonlinear and
      linear measures of a surface electromyography signal during a brief (5 second)
      and sustained (2minute) isometric maximal voluntary contraction, combined with
      superimposed electrical stimulation involving the ankle plantar flexors over five
      identical trials. In this study, we repeated the testing protocol used in our
      previous study of 10 women (age 20.9, SD=0.3 years) (Bernecke et al., 2015) in a
      group of 10 men (age 21.2, SD=0.4 years). Despite the central (sex effect;
      p<0.05, etap2>0.71, SP>70%) and peripheral fatigability (sex effect; p<0.01,
      etap2>0.8, SP>90%) during sustained isometric maximal voluntary contraction, and
      lower reliability for central activation ratio during brief (intraclass
      correlation coefficient [ICC]=0.95 for men and ICC=0.82 for women) and sustained
      maximal voluntary contraction (ICC>0.82 for men and ICC>0.66 for women) over
      ankle plantar flexors expressed in women more than in men, all the ICCs of all
      indices measured by tests assessing neuromuscular function across the five
      identical test-retest trials were found as meaningful (correlation significance
      of p<0.05 was reached) and no significant differences were found between trials
      for any of the measured variables. In conclusion, the present study demonstrated
      greater central and peripheral fatigue for female participants following
      sustained (2minute) isometric maximal voluntary contraction of the plantar flexor
      muscles for all repeated trials and indicated an acceptable agreement between
      measurements of the characteristic variables made using the three different
      devices (dynamometry, electrical stimulation, and surface electromyography) over
      time for both sexes.

PMID- 29175062
TI  - Organ/body-on-a-chip based on microfluidic technology for drug discovery.
AB  - Although animal experiments are indispensable for preclinical screening in the
      drug discovery process, various issues such as ethical considerations and species
      differences remain. To solve these issues, cell-based assays using human-derived
      cells have been actively pursued. However, it remains difficult to accurately
      predict drug efficacy, toxicity, and organs interactions, because cultivated
      cells often do not retain their original organ functions and morphologies in
      conventional in vitro cell culture systems. In the MUTAS research field, which is
      a part of biochemical engineering, the technologies of organ-on-a-chip, based on
      microfluidic devices built using microfabrication, have been widely studied
      recently as a novel in vitro organ model. Since it is possible to physically and
      chemically mimic the in vitro environment by using microfluidic device
      technology, maintenance of cellular function and morphology, and replication of
      organ interactions can be realized using organ-on-a-chip devices. So far,
      functions of various organs and tissues, such as the lung, liver, kidney, and gut
      have been reproduced as in vitro models. Furthermore, a body-on-a-chip,
      integrating multi organ functions on a microfluidic device, has also been
      proposed for prediction of organ interactions. We herein provide a background of
      microfluidic systems, organ-on-a-chip, Body-on-a-chip technologies, and their
      challenges in the future.

PMID- 29175063
TI  - Status of nucleolar channel systems in uterine secretions accurately reflects
      their prevalence-a marker for the window of implantation-in simultaneously
      obtained endometrial biopsies.
AB  - OBJECTIVE: To assess whether nucleolar channel systems (NCSs) can be detected in
      exfoliated endometrial epithelial cells (EECs) of uterine secretions and whether
      such noninvasively determined NCS status is associated with significant NCS
      prevalence in simultaneously obtained endometrial biopsies. DESIGN: Prospective
      study (December 2015-February 2017). SETTING: University-affiliated and private
      fertility clinics. PATIENT(S): Luteal-phase patients of reproductive age
      requiring endometrial biopsy for medical indications. INTERVENTION(S): Uterine
      secretion aspiration before endometrial biopsy. Cells in uterine secretions were
      spun onto slides and fixed. NCSs were identified and quantified in cells and
      paraffin-embedded tissue sections by indirect immunofluorescence. MAIN OUTCOME
      MEASURE(S): Comparison of NCS status of uterine secretions with NCS prevalence in
      biopsies. Based on NCS detection, uterine secretions were assigned a status of
      NCS-positive (n = 15) or NCS-negative (n = 7). NCS prevalence in biopsies was
      expressed as a percentage of NCSs per EECs. RESULT(S): NCSs can be detected in
      exfoliated EECs of uterine secretions. Median NCS prevalence in endometrial
      biopsies from patients with NCS-positive secretions was 41.9% (interquartile
      range [IQR], 21.1-53.9) versus 2.0% (IQR, 0-6.9) when secretions were NCS
      negative. The NCS status of secretions identified a significant difference in NCS
      prevalence of simultaneously obtained biopsies. CONCLUSION(S): NCS status of
      secretions accurately reflects NCS prevalence of biopsies, a marker for the
      implantation window. As secretion aspiration is compatible with same-day ET, our
      study provides proof of principle for a minimally invasive approach to determine
      endometrial receptivity for timing frozen ET.

PMID- 29175065
TI  - Effect of the initiation of progesterone supplementation in in vitro
      fertilization-embryo transfer outcomes: a prospective randomized controlled
      trial.
AB  - OBJECTIVE: To analyze the influence of the start point of luteal support on
      clinical pregnancy rate, implantation rate, and live birth rate of in vitro
      fertilization and embryo transfer (IVF-ET) cycles. DESIGN: Single-center
      prospective randomized controlled trial. SETTING: University-affiliated IVF unit.
      PATIENT(S): Women <=35 years of age with day 3 FSH levels <15 mIU/mL, who were
      undergoing their first IVF-ET cycles and received ovarian stimulation with the
      use of a GnRH agonist long protocol. INTERVENTION(S): The patients were
      randomized on the day of hCG trigger to receive luteal phase support either 1 day
      after oocyte retrieval (group A) or on the day of oocyte retrieval (group B).
      MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, implantation rate, miscarriage
      rate in the first trimester of pregnancy, and live birth rate per embryo transfer
      cycle. RESULT(S): Two hundred thirty-three patients were enrolled in this study:
      117 were assigned to group A and 116 to group B. The clinical pregnancy rate
      (group A vs. group B: 55.3% vs. 51.5%), implantation rate (38.4% vs. 38.0%), and
      miscarriage rate (7.7% vs. 7.5%) were similar between the two groups. The live
      birth rate also did not significantly differ between the two groups (45.7% vs.
      46.6%). CONCLUSION(S): Our study indicated that the initiation of progesterone
      supplementation 1 day after oocyte retrieval did not decrease the clinical
      pregnancy rate, implantation rate, or live birth rate in women undergoing IVF-ET
      cycles with the use of the GnRH agonist long protocol. CLINICAL TRIAL
      REGISTRATION NUMBER: ChiCTR-IPR-14005293.

PMID- 29175064
TI  - Difference between mean gestational sac diameter and crown-rump length as a
      marker of first-trimester pregnancy loss after in vitro fertilization.
AB  - OBJECTIVE: To investigate whether the difference between mean gestational sac
      diameter and crown-rump length (mGSD - CRL) is associated with first-trimester
      pregnancy loss or adverse pregnancy outcomes after in vitro fertilization (IVF)
      and to determine if mGSD - CRL is a better predictor of pregnancy loss than
      either measurement alone. DESIGN: Retrospective cohort study. SETTING: University
      hospital. PATIENT(S): A total of 1,243 IVF cycles with fresh or cryopreserved
      autologous embryo transfers resulting in singleton gestations performed at the
      University of Iowa Hospitals and Clinics from January 2005 through December 2014.
      Cycles included ultrasound measurements of mGSD and CRL at 45-56 days' gestation.
      INTERVENTION(S): Mean gestational sac diameter to crown-rump length difference.
      MAIN OUTCOME MEASURE(S): Primary outcomes were first-trimester pregnancy loss and
      gestational age at delivery. Secondary outcomes were infant birth weight and
      pregnancy complications. RESULT(S): First-trimester pregnancy loss rates were
      significantly higher in pregnancies with mGSD - CRL <5 mm (43.7%) compared with 5
      9.99 mm (15.8%), 10-14.99 mm (9.9%), and >=15 mm (7.1%). No correlations were
      found with infant birth weight, gestational age at delivery, or other pregnancy
      complications. mGSD - CRL was not a better predictor of pregnancy loss than mGSD
      or CRL alone. CONCLUSION(S): There is a strong inverse relationship between mGSD 
      CRL and first-trimester pregnancy loss in IVF patients, although the incidence
      of pregnancy loss with a mGSD - CRL <5 mm was significantly lower than previously
      reported. Small mGSD - CRL was not associated with an increased risk of
      complications in pregnancies that continued beyond 20 weeks. The association
      between mGSD, CRL, and miscarriage is complex.

PMID- 29175066
TI  - Randomized controlled trial comparing embryo culture in two incubator systems:
      G185 K-System versus EmbryoScope.
AB  - OBJECTIVE: To study whether the closed culture system, as compared with a
      benchtop incubator with similar culture conditions, has a positive impact on
      intracytoplasmic sperm injection (ICSI) outcomes. DESIGN: Randomized controlled
      trial. SETTING: University hospital. PATIENT(S): A total of 386 patients
      undergoing ICSI cycles with at least six mature oocytes were randomized.
      INTERVENTION(S): Of these patients, 195 were assigned to the group with culture
      in a time-lapse imaging (TLI) system (EmbryoScope) and 191 to the group with
      culture in the G185 K-System (G185). MAIN OUTCOME MEASURE(S): Rate of
      implantation (primary endpoint) and embryo morphology grade. RESULT(S): No
      significant differences were found in the implantation rates. The proportion of
      high-grade embryos on day 2 was significantly higher in the TLI group compared
      with the G185 group (40.4% vs. 35.2%). The impact of the incubator on embryo
      morphology remained significant in multivariate analysis, which took into account
      the woman's age, the rank of attempt, and the smoking status (TLI vs. G185: odds
      ratio = 1.27; 95% confidence interval, [1.04-1.55]). No difference was found in
      the mean number of frozen embryos, even though the total proportion of frozen
      embryos was significantly higher in the TLI group than in the G185 group (29.5%
      vs. 24.8%). CONCLUSION(S): No difference in implantation rate was found between
      the two incubators for fresh cycles. It remains to be determined whether the
      observed differences in embryo morphology and the total number of embryos
      cryopreserved would translate into higher cumulative outcomes with subsequent
      frozen embryo transfers. CLINICAL TRIAL REGISTRATION NO: NCT02722252.

PMID- 29175067
TI  - Quality of life and psychosocial and physical well-being among 1,023 women during
      their first assisted reproductive technology treatment: secondary outcome to a
      randomized controlled trial comparing gonadotropin-releasing hormone (GnRH)
      antagonist and GnRH agonist protocols.
AB  - OBJECTIVE: To compare self-reported quality of life, psychosocial well-being, and
      physical well-being during assisted reproductive technology (ART) treatment in
      1,023 women allocated to either a short GnRH antagonist or long GnRH agonist
      protocol. DESIGN: Secondary outcome of a prospective phase 4, open-label,
      randomized controlled trial. Four times during treatment a questionnaire on self
      reported physical well-being was completed. Further, a questionnaire on self
      reported quality of life and psychosocial well-being was completed at the day of
      hCG testing. SETTING: Fertility clinics at university hospitals. PATIENT(S):
      Women referred for their first ART treatment were randomized in a 1:1 ratio and
      started standardized ART protocols. INTERVENTION(S): Gonadotropin-releasing
      hormone analogue; 528 women allocated to a short GnRH antagonist protocol and 495
      women allocated to a long GnRH agonist protocol. MAIN OUTCOME MEASURE(S): Self
      reported quality of life, psychosocial well-being, and physical well-being based
      on questionnaires developed for women receiving ART treatment. RESULT(S):
      Baseline characteristics were similar, and response rates were 79.4% and 74.3% in
      the GnRH antagonist and GnRH agonist groups, respectively. Self-reported quality
      of life during ART treatment was rated similar and slightly below normal in both
      groups. However, women in the GnRH antagonist group felt less emotional (adjusted
      odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74),
      experienced less unexpected crying (AOR 0.71), and rated quality of sleep better
      (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse
      physically. CONCLUSION(S): Women in a short GnRH antagonist protocol rated
      psychosocial and physical well-being during first ART treatment better than did
      women in a long GnRH agonist protocol. However, the one item on self-reported
      general quality of life was rated similarly. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT00756028.

PMID- 29175068
TI  - Endometrial scratch injury before intrauterine insemination: is it time to re
      evaluate its value? Evidence from a systematic review and meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: To assess the impact of endometrial scratch injury (ESI) on the
      outcomes of intrauterine insemination (IUI) stimulated cycles. DESIGN: Systematic
      review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women
      undergoing one or more IUI stimulated cycles. INTERVENTION(S): Randomized
      controlled trials (RCTs) were identified by searching electronic databases. We
      included RCTs comparing ESI (i.e., intervention group) during the course of IUI
      stimulated cycle (C-ESI) or during the menstrual cycle preceding IUI treatment (P
      ESI) with controls (no endometrial scratch). The summary measures were reported
      as odds ratio (OR) with 95% confidence-interval (CI). MAIN OUTCOME MEASURE(S):
      Clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate, ectopic
      pregnancy rate, miscarriage rate. RESULT(S): Eight trials were included in the
      meta-analysis, comprising a total of 1,871 IUI cycles. Endometrial scratch injury
      was associated with a higher clinical pregnancy rate (OR 2.27) and ongoing
      pregnancy rate (OR 2.04) in comparison with the controls. No higher risk of
      multiple pregnancy (OR 1.09), miscarriage (OR 0.80), or ectopic pregnancy (OR
      0.82) was observed in patients receiving ESI. Subgroup analysis based on ESI
      timing showed higher clinical pregnancy rate (OR 2.57) and ongoing pregnancy rate
      (OR 2.27) in patients receiving C-ESI and no advantage in patients receiving P
      ESI. CONCLUSION(S): Available data suggest that ESI performed once, preferably
      during the follicular phase of the same cycle of IUI with flexible aspiration
      catheters, may improve clinical pregnancy and ongoing pregnancy rates in IUI
      cycles. Endometrial scratch injury does not appear to increase the risk of
      multiple pregnancy, miscarriage, or ectopic pregnancy.

PMID- 29175069
TI  - Quality of life must be taken into account when assessing the efficacy of
      infertility treatment.

PMID- 29175070
TI  - Ovarian tissue transplantation and leukemia.

PMID- 29175071
TI  - IcarisideII improves left ventricular remodeling in spontaneously hypertensive
      rats by inhibiting the ASK1-JNK/p38 signaling pathway.
AB  - Inhibition or removal of excess reactive oxygen species can effectively protect
      cellular function or reduce cell death because oxidative stress is the main cause
      of cellular damage in many diseases. The flavonoid compound IcarisideII having a
      slight inhibitory effect on PDE5, is the main active components of epimedium in
      vivo and has a wide range of pharmacological effects on oxidation and apoptosis.
      However, whether IcarisideII has the same protective effect on ventricular
      remodeling in spontaneously hypertensive rats (SHR) is unknown. We found that
      compared with WKY rats, SHRs exhibited noticeable arterial hypertension.
      Additionally, echocardiography showed that the diameter of the left ventricle was
      enlarged, wall thickness was increased, and ejection fraction and short axis
      shortening rate were reduced. H&E staining demonstrated that SHR cells were
      disordered and noticeably hypertrophic. Masson trichrome staining revealed
      significant myocardial fibrosis in the myocardium. Tunel staining indicated that
      4.39 times the percent of apoptotic cells were present in SHRs compared to WKY
      rats. In our study, intra-gastric administration of IcarisideII decreased blood
      pressure, promoted heart function recovery and improved ventricular remodeling in
      SHRs. Additionally, it reduced myocardial fibrosis, inhibited myocardial
      apoptosis, decreased the generation of reactive oxygen species and improved SOD
      activity. IcarisideII down-regulated the activation of the oxidative stress
      associated proteins ASK1, p38 and JNK; inhibited the expression of p53, Bax and
      cleaved-caspase3 in the mitochondrial apoptosis pathway; and up-regulated the
      expression of Bcl-2. In conclusion, this study indicates that IcarisideII can
      inhibit myocardial apoptosis and improve left ventricular remodeling in SHRs. It
      can be inferred that this mechanism may be related to the inhibition of the ASK1
      JNK/p38 signaling pathway.

PMID- 29175072
TI  - Capsaicin prevents mitochondrial damage, protects cardiomyocytes subjected to
      anoxia/reoxygenation injury mediated by 14-3-3eta/Bcl-2.
AB  - Capsaicin(Cap) is an active component of chili peppers that is extracted from
      capsicum plants. Recent studies have reported that Cap can ameliorate myocardial
      ischemia/reperfusion(I/R) injury. Mitochondria play an important role in pathways
      of apoptosis induced by myocardial I/R injury. However, the underlying mechanisms
      of Cap that improve mitochondrial function during I/R injury is not yet
      understood. The aim of this study was to evaluate whether Cap regained normal
      mitochondrial function in myocardial I/R injury, and to further explore the
      underlying mechanisms of action involved. In this study, an acute myocardial
      anoxia/reoxygenation(A/R) injury model was established using H9c2 cells. The cell
      viability was detected by MTS assay. LDH activity, mitochondrial permeability
      transition pores(mPTP) opening, and caspase-3 activity were analyzed using an
      ultra violet spectrophotometer. Levels of intracellular reactive oxygen species
      and apoptosis were evaluated by flow cytometry. Western blot analysis was used to
      determine the expression of 14-3-3eta, Bcl-2, and Bax. The data showed that
      pretreatment with Cap decreased LDH release and increased cell viability in H9c2
      cells that underwent A/R. Cap pretreatment significantly attenuated generation of
      reactive oxygen species, inhibited mPTP opening and caspase-3 activation,
      downregulated Bax, upregulated 14-3-3eta and Bcl-2, and ultimately reduced
      apoptosis in H9c2 cells that underwent A/R. Moreover, 14-3-3etaRNAi adenovirus
      markedly eliminated the protective effects of Cap in H9c2 cells that underwent
      A/R. In addition, ABT-737(inhibitor of Bcl-2) significantly eliminated Cap
      protection. Taken together, the present study suggested that the cardioprotective
      effect of Cap against A/R injury involves the 14-3-3eta pathway and prevention of
      mitochondrial damage.

PMID- 29175073
TI  - Von Economo neurons of the anterior cingulate across the lifespan and in
      Alzheimer's disease.
AB  - BACKGROUND: Throughout the human aging lifespan, neurons acquire an unusually
      high burden of wear and tear; this is likely why age is considered the strongest
      risk factor for the development of Alzheimer's Disease (AD). Von Economo neurons
      (VENs) are rare, spindle-shaped cells mostly populated in anterior cingulate
      cortex. In a prior study, "SuperAgers" (individuals older than 80 years of age
      with outstanding memory ability) showed higher VEN densities compared to elderly
      controls with average memory, and those with amnestic Mild Cognitive Impairment
      (aMCI). The intrinsic vulnerabilities of these neurons are unclear, and their
      contribution to neurodegeneration is unknown. The current study investigated the
      influence of age and the severity of Alzheimer's disease (AD) on VEN density.
      METHODS: VEN and total neuronal densities were quantitated using unbiased
      stereological methods in the anterior cingulate cortex of postmortem samples from
      the following subject groups: younger controls (age 20-60), SuperAgers,
      cognitively average elderly controls (age 65+), individuals diagnosed antemortem
      with aMCI, and individuals diagnosed antemortem with dementia of AD (N = 5, per
      group). RESULTS: The AD group showed significantly lower VEN density compared to
      younger and older controls (p < .05), but not compared to the aMCI group, and
      VENs bearing neurofibrillary tangles were discovered in AD cases. The aMCI group
      showed lower VEN density than elderly controls, but this was not significant.
      There was a significant negative correlation between VEN density and Braak stages
      of AD (p < .001). Consistent with prior findings, SuperAgers showed highest mean
      VEN density, even when compared to younger cases. CONCLUSIONS: VENs in human
      anterior cingulate cortex are vulnerable to AD pathology, particularly in later
      stages of pathogenesis. Their densities do not change throughout aging in
      individuals with average cognition, and they are more numerous in SuperAgers.

PMID- 29175075
TI  - Aqueous chlorhexidine for surgical hand disinfection?

PMID- 29175074
TI  - Staphylococcus aureus and Staphylococcus epidermidis infections on implants.
AB  - Infections are one of the main reasons for removal of implants from patients, and
      usually need difficult and expensive treatments. Staphylococcus aureus and
      Staphylococcus epidermidis are the most frequently detected pathogens. We
      reviewed the epidemiology and pathogenesis of implant-related infections.
      Relevant studies were identified by electronic searching of the following
      databases: PubMed, ScienceDirect, Academic Google, and CAPES Journal Portal. This
      review reports epidemiological studies of implant infections caused by S. aureus
      and S. epidermidis. We discuss some methodologies used in the search for new
      compounds with antibiofilm activity and the main strategies for biomaterial
      surface modifications to avoid bacterial plaque formation and consequent
      infection. S. aureus and S. epidermidis are frequently involved in infections in
      catheters and orthopaedic/breast implants. Different methodologies have been used
      to test the potential antibiofilm properties of compounds; for example, crystal
      violet dye is widely used for in-vitro biofilm quantification due to its low cost
      and good reproducibility. Changes in the surface biomaterials are necessary to
      prevent biofilm formation. Some studies have investigated the immobilization of
      antibiotics on the surfaces of materials used in implants. Other approaches have
      been used as a way to avoid the spread of bacterial resistance to antimicrobials,
      such as the functionalization of these surfaces with silver and natural
      compounds, as well as the electrical treatment of these substrates.

PMID- 29175076
TI  - Fluoroquinolone prophylaxis in haematopoietic bone marrow transplantation: a
      driver for antimicrobial resistance.

PMID- 29175077
TI  - Detection limit of Mycobacterium chimaera in water samples for monitoring medical
      device safety: insights from a pilot experimental series.
AB  - BACKGROUND: A growing number of Mycobacterium chimaera infections after
      cardiosurgery have been reported by several countries. These potentially fatal
      infections were traced back to contaminated heater-cooler devices (HCDs), which
      use water as a heat transfer medium. Aerosolization of water contaminated with M.
      chimaera from HCDs enables airborne transmission to patients undergoing open
      chest surgery. Infection control teams test HCD water samples for mycobacterial
      growth to guide preventive measures. The detection limit of M. chimaera in water
      samples, however, has not previously been investigated. AIM: To determine the
      detection limit of M. chimaera in water samples using laboratory-based serial
      dilution tests. METHODS: An M. chimaera strain representative of the
      international cardiosurgery-associated M. chimaera outbreak was used to generate
      a logarithmic dilution series. Two different water volumes, 50 and 1000mL, were
      inoculated, and, after identical processing (centrifugation, decantation, and
      decontamination), seeded on mycobacteria growth indicator tube (MGIT) and
      Middlebrook 7H11 solid media. FINDINGS: MGIT consistently showed a lower
      detection limit than 7H11 solid media, corresponding to a detection limit of
      >=1.44 * 104cfu/mL for 50mL and >=2.4cfu/mL for 1000mL water samples. Solid media
      failed to detect M. chimaera in 50mL water samples. CONCLUSION: Depending on
      water volume and culture method, major differences exist in the detection limit
      of M. chimaera. In terms of sensitivity, 1000mL water samples in MGIT media
      performed best. Our results have important implications for infection prevention
      and control strategies in mitigation of the M. chimaera outbreak and healthcare
      water safety in general.

PMID- 29175078
TI  - Limbic brain structures and burnout-A systematic review.
AB  - More profound understanding of the relationship between the burnout and the
      limbic system function can provide better insight into brain structures
      associated with the burnout syndrome. The objective of this review is to explore
      all evidence of limbic brain structures associated with the burnout syndrome. In
      total, 13 studies were selected. Four of them applied the neuroimaging technology
      to investigate the sizes/volumes of the limbic brain structures of burnout
      patients. Six other studies were to investigate the hypothalamus-pituitary
      adrenal (HPA) axis of burnout patients. Based on the results of the studies on
      the HPA-axis and neuroimaging of the limbic brain structures, one can see great
      impact of the chronic occupational stress on the limbic structures in terms of
      HPA dysregulation, a decrease of BDNF, impaired neurogenesis and limbic
      structures atrophy. It can be concluded that chronic stress inhibits the feedback
      control pathway in the HPA axis, causes the decrease of brain-derived
      neurotrophic factor (BDNF), then impaired neurogenesis and eventually neuron
      atrophy.

PMID- 29175079
TI  - Semiconducting polymer-based nanoparticles with strong absorbance in NIR-II
      window for in vivo photothermal therapy and photoacoustic imaging.
AB  - Near-infrared (NIR) light-induced photothermal therapy (PTT) has attracted much
      interest in recent years. In the NIR region, tissue penetration ability of the
      second biological near-infrared window (1000-1350 nm) is recognized to be
      stronger than that of the first window (650-950 nm). However, NIR light absorbers
      in the second NIR region (NIR-II) have been scant even though various NIR light
      absorbers in the first NIR region (NIR-I) have been widely explored. In this
      work, a thieno-isoindigo derivative-based semiconducting polymer, PBTPBF-BT, were
      formulated into PEGylated nanoparticles. The obtained nanoparticle NPPBTPBF-BT
      exhibited strong absorption in NIR-II region, inherent high photothermal
      conversion efficacy, and excellent photostability. The in vitro and in vivo PTT
      study employing 1064 nm laser in NIR-II window revealed that NPPBTPBF-BT could
      efficiently ablate tumor cell at a power density of 0.42 W/cm2 (the skin
      tolerance threshold value). Moreover, NPPBTPBF-BT with excellent photostability
      exhibited enhanced photoacoustic (PA) imaging of tumor in living mice, suggesting
      the great probability of using NPPBTPBF-BT for in vivo PA imaging-guided PTT in
      the NIR-II window.

PMID- 29175080
TI  - Targeted iron nanoparticles with platinum-(IV) prodrugs and anti-EZH2 siRNA show
      great synergy in combating drug resistance in vitro and in vivo.
AB  - Resistance to platinum agents is challenging in cancer treatment with platinum
      drugs. Such resistant cells prevent effective platinum accumulation intracellular
      and alter cellular adaptations to survive from cytotoxicity by regulating
      corresponding proteins expression. Ideal therapeutics should combine resolution
      to these pump and non-pump relevant resistance of cancer cells to achieve high
      efficacy and low side effect. Fe3O4 nanocarrier loaded with drugs could enter
      cells in a more efficient endocytosis manner which circumvents pump-relevant drug
      resistance. EZH2 protein which was previously found to be over-expressed in drug
      resistant cancer cells was reported to be involved in platinum drug resistance
      and play a vital role in anti-apoptosis pathways. Here, we report Fe3O4
      nanoparticles loaded with siEZH2 (siRNA), a platinum prodrug in +4 oxidation
      state (cis, cis, trans-diamminedichlorodisuccinato-platinum-(IV), namely Pt(IV))
      and luteinizing hormone-releasing hormone (LHRH) targeting polypeptides. Results
      show that targeted nanoparticles loading with siEZH2 synergize with Pt(IV) and
      result in similar cell killing performance to A2780/DDP cells (cisplatin
      resistant) compared with non-siEZH2 loaded nanoparticles to A2780 cells
      (cisplatin sensitive). Thus, this Fe3O4@PEI-Pt(IV)-PEG-LHRH@siEZH2 nanoparticles
      reverse the cisplatin resistance from the pump and non-pump relevant aspects,
      fully taking advantage of nanocarrier system.

PMID- 29175082
TI  - SnWO4-based nanohybrids with full energy transfer for largely enhanced
      photodynamic therapy and radiotherapy.
AB  - The "partial matching" between upconversion nanoparticle (UCNP) emission and
      absorption by photosensitizers (PSs) often leads to a theoretically reduced
      therapeutic efficiency in UC-based photodynamic therapy (PDT) strategies in which
      the chosen PSs have limited capabilities and are unable to utilize all the near
      infrared-upconverted light. In this study, needle-like SnWO4 nanocrystals (SWs)
      with a broad UV-vis absorption region were synthesized to solve the problem.
      After covalent conjugation with UCNPs, all the UCNP-emitted light was effectively
      absorbed by SWs, triggering the type-I PDT process to activate ROS maxima. The
      unique nanostructure of the as-formed UCNP-SnWO4 nanohybrids (USWs) also enhanced
      the receiving light intensities of SW, which further boosted the antitumor
      efficacy. Meanwhile, the strong X-ray attenuation capacity of both tungsten and
      tin elements qualified the USWs as excellent radio-sensitizers for radiotherapy
      (RT) enhancement, which played a complementary role with PDT treatment because
      PDT-mediated induction arrested the cells in the G0-G1 cell cycle phase, and RT
      was more damaging toward cells in the G2/M phase. The remarkably enhanced UC
      PDT/RT efficiency of USWs was next validated in vitro and in vivo, and the
      combined NIR light and ionizing irradiation treatment completely suppressed tumor
      growth, revealing its great potential as an efficient anticancer therapeutic
      agent against solid tumors.

PMID- 29175081
TI  - Epithelial-mesenchymal crosstalk influences cellular behavior in a 3D alveolus
      fibroblast model system.
AB  - Interactions between lung epithelium and interstitial fibroblasts are
      increasingly recognized as playing a major role in the progression of several
      lung pathologies, including cancer. Three-dimensional in vitro co-culture systems
      offer tissue-relevant platforms to study the signaling interplay between diseased
      and healthy cell types. Such systems provide a controlled environment in which to
      probe the mechanisms involved in epithelial-mesenchymal crosstalk. To
      recapitulate the native alveolar tissue architecture, we employed a cyst
      templating technique to culture alveolar epithelial cells on photodegradable
      microspheres and subsequently encapsulated the cell-laden spheres within poly
      (ethylene glycol) (PEG) hydrogels containing dispersed pulmonary fibroblasts. A
      fibroblast cell line (CCL-210) was co-cultured with either healthy mouse alveolar
      epithelial primary cells or a cancerous alveolar epithelial cell line (A549) to
      probe the influence of tumor-stromal interactions on proliferation, migration,
      and matrix remodeling. In 3D co-culture, cancerous epithelial cells and
      fibroblasts had higher proliferation rates. When examining fibroblast motility,
      the fibroblasts migrated faster when co-cultured with cancerous A549 cells.
      Finally, a fluorescent peptide reporter for matrix metalloproteinase (MMP)
      activity revealed increased MMP activity when A549s and fibroblasts were co
      cultured. When MMP activity was inhibited or when cells were cultured in gels
      with a non-degradable crosslinker, fibroblast migration was dramatically
      suppressed, and the increase in cancer cell proliferation in co-culture was
      abrogated. Together, this evidence supports the idea that there is an exchange
      between the alveolar epithelium and surrounding fibroblasts during cancer
      progression that depends on MMP activity and points to potential signaling routes
      that merit further investigation to determine targets for cancer treatment.

PMID- 29175083
TI  - Development of a theranostic prodrug for colon cancer therapy by combining ligand
      targeted delivery and enzyme-stimulated activation.
AB  - The high incidence of colorectal cancer worldwide is currently a major health
      concern. Although conventional chemotherapy and surgery are effective to some
      extent, there is always a risk of relapse due to associated side effects,
      including post-surgical complications and non-discrimination between cancer and
      normal cells. In this study, we developed a small molecule-based theranostic
      system, Gal-Dox, which is preferentially taken up by colon cancer cells through
      receptor-mediated endocytosis. After cancer-specific activation, the active drug
      Dox (doxorubicin) is released with a fluorescence turn-on response, allowing both
      drug localization and site of action to be monitored. The therapeutic potency of
      Gal-Dox was also evaluated, both in vivo and ex vivo, thus illustrating the
      potential of Gal-Dox as a colorectal cancer theranostic with great specificity.

PMID- 29175085
TI  - Ventilator Management and Respiratory Care After Cardiac Arrest: Oxygenation,
      Ventilation, Infection, and Injury.
AB  - Return of spontaneous circulation after cardiac arrest results in a systemic
      inflammatory state called the post-cardiac arrest syndrome, which is
      characterized by oxidative stress, coagulopathy, neuronal injury, and organ
      dysfunction. Perturbations in oxygenation and ventilation may exacerbate
      secondary injury after cardiac arrest and have been shown to be associated with
      poor outcome. Further, patients who experience cardiac arrest are at risk for a
      number of other pulmonary complications. Up to 70% of patients experience early
      infection after cardiac arrest, and the respiratory tract is the most common
      source. Vigilance for early-onset pneumonia, as well as aggressive diagnosis and
      early antimicrobial agent administration are important components of critical
      care in this population. Patients who experience cardiac arrest are at risk for
      the development of ARDS. Risk factors include aspiration, pulmonary contusions
      (from chest compressions), systemic inflammation, and reperfusion injury. Early
      evidence suggests that they may benefit from ventilation with low tidal volumes.
      Meticulous attention to mechanical ventilation, early assessment and optimization
      of respiratory gas exchange, and therapies targeted at potential pulmonary
      complications may improve outcomes after cardiac arrest.

PMID- 29175084
TI  - Manipulating human dendritic cell phenotype and function with targeted porous
      silicon nanoparticles.
AB  - Dendritic cells (DC) are the most potent antigen-presenting cells and are
      fundamental for the establishment of transplant tolerance. The Dendritic Cell
      Specific Intracellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN; CD209)
      receptor provides a target for dendritic cell therapy. Biodegradable and high
      surface area porous silicon (pSi) nanoparticles displaying anti-DC-SIGN
      antibodies and loaded with the immunosuppressant rapamycin (Sirolimus) serve as a
      fit-for-purpose platform to target and modify DC. Here, we describe the
      fabrication of rapamycin-loaded DC-SIGN displaying pSi nanoparticles, the uptake
      efficiency into DC and the extent of nanoparticle-induced modulation of phenotype
      and function. DC-SIGN antibody displaying pSi nanoparticles favourably targeted
      and were phagocytosed by monocyte-derived and myeloid DC in whole human blood in
      a time- and dose-dependent manner. DC preconditioning with rapamycin-loaded
      nanoparticles, resulted in a maturation resistant phenotype and significantly
      suppressed allogeneic T-cell proliferation.

PMID- 29175086
TI  - Re-examining Permissive Hypercapnia in ARDS: A Narrative Review.
AB  - Lung-protective ventilation (LPV) has become the cornerstone of management in
      patients with ARDS. A subset of patients is unable to tolerate LPV without
      significant CO2 elevation. In these patients, permissive hypercapnia is used.
      Although thought to be benign, it is becoming increasingly evident that elevated
      CO2 levels have significant physiological effects. In this narrative review, we
      highlight clinically relevant end-organ effects in both animal models and
      clinical studies. We also explore the association between elevated CO2, acute cor
      pulmonale, and ICU mortality. We conclude with a brief review of alternative
      therapies for CO2 management currently under investigation in patients with
      moderate to severe ARDS.

PMID- 29175087
TI  - Iso-risk air no decompression limits after scoring marginal decompression
      sickness cases as non-events.
AB  - Decompression sickness (DCS) in humans is associated with reductions in ambient
      pressure that occur during diving, aviation, or certain manned spaceflight
      operations. Its signs and symptoms can include, but are not limited to, joint
      pain, radiating abdominal pain, paresthesia, dyspnea, general malaise, cognitive
      dysfunction, cardiopulmonary dysfunction, and death. Probabilistic models of DCS
      allow the probability of DCS incidence and time of occurrence during or after a
      given hyperbaric or hypobaric exposure to be predicted based on how the gas
      contents or gas bubble volumes vary in hypothetical tissue compartments during
      the exposure. These models are calibrated using data containing the pressure and
      respired gas histories of actual exposures, some of which resulted in DCS, some
      of which did not, and others in which the diagnosis of DCS was not clear. The
      latter are referred to as marginal DCS cases. In earlier works, a marginal DCS
      event was typically weighted as 0.1, with a full DCS event being weighted as 1.0,
      and a non-event being weighted as 0.0. Recent work has shown that marginal DCS
      events should be weighted as 0.0 when calibrating gas content models. We confirm
      this indication in the present work by showing that such models have improved
      performance when calibrated to data with marginal DCS events coded as non-events.
      Further, we investigate the ramifications of derating marginal events on model
      prescribed air diving no-stop limits.

PMID- 29175088
TI  - Constitutive up-regulation of Turandot genes rather than changes in acclimation
      ability is associated with the evolutionary adaptation to temperature
      fluctuations in Drosophila simulans.
AB  - Most research on thermal adaptation of ectotherms is based on experiments
      performed at constant temperatures. However, for short-lived insects daily
      fluctuations of temperature could be an important environmental parameter
      involved in evolutionary adaptation to thermal heterogeneity. In this study we
      investigated the mechanisms underlying evolutionary adaptation to daily
      fluctuating temperatures. We studied replicated selection lines of Drosophila
      simulans evolved in a constant or a daily fluctuating thermal regime. Previous
      studies of these lines have shown clear acclimation benefits to heat tolerance
      induced by the fluctuating regime. First, we tested the existence of an evolved
      circadian controlled adjustment of heat resistance in selected flies. This was
      done by investigating the daily variation in time to heat knockdown in flies from
      both selection regimes when exposed to either a constant or a daily fluctuating
      thermal regime for a single generation. While daily variation in heat resistance
      was found, the results suggest that there was neither an evolved adaptive
      circadian controlled adjustment of heat resistance nor a continuous acclimation
      response induced by fluctuating temperatures in these lines. Second, in order to
      reveal functional candidates for adaptation to the fluctuating thermal regime, we
      investigated the global transcriptomic response to a high temperature exposure in
      flies from both regimes. We found that flies selected both in constant and
      fluctuating thermal regimes responded similarly to increasing temperature.
      However, we found that evolutionary adaptation to the fluctuating thermal regime
      led to transcriptional enrichment of the GO terms eggshell chorion assembly and
      cellular response to heat. The latter category was constituted by a constitutive
      up-regulation of four Turandot genes and not heat shock protein genes, suggesting
      that Turandot genes could play a prominent role for adaptation to daily
      fluctuating thermal conditions.

PMID- 29175089
TI  - Effects of gender, age, and nutrition on circadian locomotor activity rhythms in
      the flesh fly Sarcophaga crassipalpis.
AB  - In many animal species, circadian rhythms of behavior are not constant throughout
      the lifetime of the individual but rather exhibit at least some degree of
      plasticity. In the present study, we have examined the potential influences of
      gender, age, and nutrition (presence or absence of liver) on the expression of
      circadian locomotor activity rhythms in the flesh fly Sarcophaga crassipalpis. We
      found no significant differences in endogenous circadian period under constant
      dark conditions with respect to gender, nutrition, or age for the duration of our
      experiments. On the other hand, both male and female flesh flies, as expected,
      were predominantly diurnal under light-dark cycles, but the pattern of
      entrainment differed between the sexes. Females also displayed higher activity
      levels than males. Also, in contrast with males, female activity levels increased
      with age. Moreover, females exhibited an extraordinary, but transient (one to
      three days), departure from diurnality which we characterize as "extended dark
      activity" (EDA). This phenomenon appeared as a continuous bout of locomotor
      activity that extended at least three hours into the early half of the dark phase
      at levels at least twice the median of the overall locomotor activity for the
      individual fly. EDA occurred as an age-dependent response to liver consumption,
      never appearing prior to day 4 post-eclosion but, thereafter, transpiring within
      one or two days after a 48-h exposure to liver. These results suggest a linkage
      between physiological events associated with egg provisioning and locomotor
      activity in the anautogenous flesh fly. Furthermore, our findings identify the
      existence of multiple influences on the expression of circadian clock-regulated
      behavior.

PMID- 29175091
TI  - Phosphoprotein DIGE profiles reflect blast differentiation, cytogenetic risk
      stratification, FLT3/NPM1 mutations and therapy response in acute myeloid
      leukaemia.
AB  - : Acute myeloid leukaemia (AML) is an aggressive blood cancer characterized by a
      distinct block in differentiation of myeloid progenitors, recurrent chromosomal
      translocations and gene mutations of which >50% involve signal transduction
      through dysregulated kinases and phosphatases. In search for novel protein
      biomarkers for disease stratification we investigated the phosphoproteome in
      leukaemic cells from 62 AML patients at time of diagnosis using immobilized metal
      affinity chromatography, protein separation by two-dimensional differential gel
      electrophoresis (2D-DIGE) and mass spectrometry before validation by selected
      reaction monitoring (SRM). Unsupervised clustering found 27 phosphoproteins
      significantly discriminating patients according to leukaemic cell differentiation
      (French-American-British (FAB) classification), cytogenetic and mutational (FLT3,
      NPM1) status or response to chemotherapy. Monocytic differentiation (FAB M4-M5)
      correlated with enrichment of proteins involved in apoptosis (MOES, ANXA5 and
      EFHD2). TALDO, a protein associated with thrombocytopenia if down-regulated, was
      elevated in patients with wild type NPM1 compared to patients with NPM1 mutation.
      This study demonstrates the potential of quantitative proteomics in AML
      classification and risk stratification. BIOLOGICAL SIGNIFICANCE: Patients
      diagnosed with AML are currently categorized according to cellular morphology,
      cytogenetic alterations and mutations, although the majority of these cellular
      and genetic alterations have no or unsolved impact on therapy selection or
      prognosis. We therefore explored the phosphoproteome for abundance changes
      associated with traditional classifiers to unravel patterns that could stratify
      patients at the protein level. MOES, ANXA5 and EFHD2 were confirmed by SRM to be
      correlated to monocytic differentiation, whilst TALDO was elevated in NPM1 wild
      type patients.

PMID- 29175090
TI  - Effect of fibrinogen, fibrin, and fibrin degradation products on transendothelial
      migration of leukocytes.
AB  - In spite of numerous studies on the involvement of fibrinogen in transendothelial
      migration of leukocytes and thereby inflammation, there is still no clear
      understanding of which fibrin(ogen) species can stimulate leukocyte
      transmigration. Although we have previously proposed that interaction of fibrin
      with the VLDL receptor (VLDLR) promotes leukocyte transmigration, there is no
      direct experimental evidence for the involvement of fibrin in this process. To
      address these questions, we performed systematic studies of interaction of VLDLR
      with fibrinogen, fibrin, and their isolated recombinant BbetaN- and betaN
      domains, respectively, and the effect of various fibrin(ogen) species on
      transendothelial migration of leukocytes. The results obtained revealed that
      freshly purified fibrinogen does not interact with VLDLR in solution and has
      practically no effect on leukocyte transmigration. They also indicate that the
      VLDLR-binding site is cryptic in fibrinogen and becomes accessible upon its
      adsorption onto a surface or upon its conversion into fibrin. We also found that
      the D-D:E1 complex and higher molecular mass fibrin degradation products, as well
      as soluble fibrin and fibrin polymers (clots) anchored to the endothelial
      monolayer, promote leukocyte transmigration mainly through the VLDL receptor
      dependent pathway. Thus, the results of the present study suggest that fibrin
      degradation products and soluble fibrin that may be present in the circulation in
      vivo, as well as fibrin clots that may be deposited on the surface of inflamed
      endothelium, promote leukocyte transmigration. These findings further clarify the
      molecular mechanisms underlying the fibrin-VLDLR-dependent pathway of leukocyte
      transmigration and provide an explanation for a possible (patho)physiological
      role of this pathway.

PMID- 29175092
TI  - Differences in resistance to nitrogen and phosphorus deficiencies explain male
      biased populations of poplar in nutrient-deficient habitats.
AB  - : In most forest soils, the availability of nitrogen (N) and phosphorus (P)
      nutrients is low and unable to meet the requirement of tree growth. In the past
      decades, sex-based differences in poplar have been investigated in morphology and
      physiology. Proteomic techniques provide new insights into sex-specific
      differences at the molecular level. This review gives a comparative overview of
      the effects of N and P deficiencies on poplar physiological and proteomic
      characteristics. Male poplars are more efficient at photosynthesis and nutrient
      usage than females. Proteins related to carbohydrate metabolism, defence
      responses and transcription and translation processes are changed to adapt
      diversely in males and females. These results provide evidence that male poplar
      have better resistance to nutrient-limiting conditions than females, which may be
      reasonable for the male-biased sex ratio in nutrient-deficient habitats.
      Furthermore, this review also discusses the potential growth-defence trade-offs
      in male and female poplar coping with nutrient limitations. BIOLOGICAL
      SIGNIFICANCE: In the past decades, the physiological and molecular responses of
      individual trees exposed to nutrient deficiency have been well studied. An
      important model woody plant, Populus, is dioecious and shows a male-biased sex
      ratio in nutrient-deficient habitats. Individually, different responses to
      nutrient limitation between the sexes determine the bias of population sex
      ratios. Proteomic techniques provide new insights into sex-based differences in
      the molecular mechanisms underlying nutrient deficiency. This review gives a
      comparative overview of the identification of nitrogen and phosphorus deficiency
      effects on physiological and proteomic characteristics. Male poplars are more
      resistant and have a smaller range of protein changes than females in response to
      N and P deficiency, which explains the observed male-biased sex ratios to a
      certain extent. Furthermore, this review also discusses the possible growth
      defense trade-offs in male and female poplars coping with nutrient deficiency.

PMID- 29175093
TI  - The blind mind: No sensory visual imagery in aphantasia.
AB  - For most people the use of visual imagery is pervasive in daily life, but for a
      small group of people the experience of visual imagery is entirely unknown.
      Research based on subjective phenomenology indicates that otherwise healthy
      people can completely lack the experience of visual imagery, a condition now
      referred to as aphantasia. As congenital aphantasia has thus far been based on
      subjective reports, it remains unclear whether individuals are really unable to
      imagine visually, or if they have very poor metacognition - they have images in
      their mind, but are blind to them. Here we measured sensory imagery in
      subjectively self-diagnosed aphantasics, using the binocular rivalry paradigm, as
      well as measuring their self-rated object and spatial imagery with multiple
      questionnaires (VVIQ, SUIS and OSIQ). Unlike, the general population,
      experimentally naive aphantasics showed almost no imagery-based rivalry priming.
      Aphantasic participants' self-rated visual object imagery was significantly below
      average, however their spatial imagery scores were above average. These data
      suggest that aphantasia is a condition involving a lack of sensory and phenomenal
      imagery, and not a lack of metacognition. The possible underlying neurological
      cause of aphantasia is discussed as well as future research directions.

PMID- 29175094
TI  - Application of optimal control to the onchocerciasis transmission model with
      treatment.
AB  - In this paper, we present a model for onchocerciasis that considers mass
      administration of ivermectin, contact prevention controls and vector elimination.
      The model equilibria are computed and stability analysis carried out in terms of
      the basic reproduction number R0. The model is found to exhibit a backward
      bifurcation so that for R0 less than unity is not sufficient to eradicate the
      disease from the population and the need is to lower R0 to below a certain
      threshold, R0c for effective disease control. The model is fitted to data on
      individuals with onchocerciasis in Ghana. A sensitivity analysis reveals that the
      parameters with the most control over the epidemic are the vector death rate and
      the effective contact rates between susceptible individuals and infected vector
      and susceptible vector with infected individuals. This suggests that programs
      aimed controlling vector will be significantly more effective in combating the
      disease. Optimal control theory is applied to investigate optimal control
      strategies for controlling onchocerciasis using insect repellent and both
      insecticide and larvicide as system control variables. We use Pontryagin's
      Maximum Principle to show the necessary conditions for the optimal control of
      onchocerciasis. Numerical simulations of the model show that restricted and
      proper use of control measures might considerably decrease the number of
      infections in the human population.

PMID- 29175095
TI  - Phylogeny and biogeography of East Asian evergreen oaks (Quercus section
      Cyclobalanopsis; Fagaceae): Insights into the Cenozoic history of evergreen broad
      leaved forests in subtropical Asia.
AB  - The evolutionary history of Quercus section Cyclobalanopsis, a dominant lineage
      in East Asian evergreen broadleaved forests (EBLFs), has not been comprehensively
      studied using molecular tools. In this study, we reconstruct the first
      comprehensive phylogeny of this lineage using a genomic approach (restriction
      site associated DNA sequencing, RAD-seq), sampling 35 of the ca. 90 species
      currently recognized, representing all main morphological groups of section
      Cyclobalanopsis. In addition, 10 other species of Quercus and two outgroups were
      also sampled. Divergence times were estimated using a relaxed clock model and two
      fossil calibrations. Ancestral areas and dispersal routes were inferred using
      statistical dispersal-vicariance analysis and the dispersal-extinction
      cladogenesis (DEC) model. The phylogeny of Quercus section Cyclobalanopsis
      demonstrates the section to be monophyletic, comprising two main lineages and six
      subclades that are well supported by anatomical traits. Biogeographical
      reconstructions indicate that the wide northern hemisphere distribution of
      Quercus was disrupted in the Late Eocene, leading to the main extant groups at
      about 33 Ma. The earliest divergences in section Cyclobalanopsis correspond to
      the phased uplift of the Himalayas and lateral extrusion of Indochina at the
      transition of the Oligocene and Miocene, where the highest rate of
      diversification occurred in the late Miocene. Dispersal from Sino-Himalaya and
      the Palaeotropics to Sino-Japan in the Miocene was facilitated by the increased
      intensity of East Asian summer monsoons and by the Middle Miocene Climatic
      Optimum. Our results highlight the importance of climatic changes and Indo
      Eurasian collision-induced tectonic activities from the Neogene onward to the
      spatial-temporal diversification patterns of Asian EBLF lineages.

PMID- 29175096
TI  - Budgetary Impact of Telotristat Ethyl, a Novel Treatment for Patients with
      Carcinoid Syndrome Diarrhea: A US Health Plan Perspective.
AB  - PURPOSE: Telotristat ethyl (TE) was recently approved for carcinoid syndrome
      diarrhea (CSD) in patients not adequately controlled with somatostatin analog
      long-acting release (SSA LAR) therapy alone. A budget impact model was developed
      to determine the short-term affordability of reimbursing TE in a US health plan.
      METHODS: A budget impact model compared health care costs when CSD is managed per
      current treatment patterns (SSA LAR, reference drug scenario) versus when TE is
      incorporated in the treatment algorithm (SSA LAR + TE, new drug scenario).
      Prevalence of CSD, proportion of patients not adequately controlled on SSA LAR,
      monthly treatment costs (pharmacy and medical), and treatment efficacy were
      derived from the literature. In the reference drug scenario, an escalated monthly
      dose of SSA LAR therapy of 40 mg was assumed to treat patients with CSD not
      adequately controlled on the labeled dose of SSA LAR. In the new drug scenario,
      TE was added to the maximum labeled monthly dose of SSA LAR therapy of 30 mg. The
      incremental budget impact was calculated based on an assumed TE market uptake of
      28%, 42%, and 55% during Years 1, 2, and 3, respectively. One-way sensitivity
      analyses were conducted to test model assumptions. FINDINGS: A hypothetical
      health plan of 1 million members was estimated to have 42 prevalent CSD patients
      of whom 17 would be inadequately controlled on SSA LAR therapy. The monthly
      medical cost per patient not adequately controlled on SSA LAR in addition to
      pharmacotherapy was estimated to be $3946 based on the literature. Based on the
      observed treatment response in a clinical trial of 20% and 44% for the base case
      reference and new drug scenarios, total per patient per month costs were
      estimated to be $7563 and $11,205, respectively. Total annual costs in the new
      drug scenario were estimated to be $2.3 to $2.5 million during the first 3 years.
      The overall incremental annual costs were estimated to be $154,000 in Year 1,
      $231,000 in Year 2, and $302,000 in Year 3. This translated to an incremental per
      patient per month cost of $0.013, $0.019, and $0.025 for Years 1, 2, and 3. These
      results remained robust in 1-way sensitivity analyses. IMPLICATIONS: The
      availability of TE for patients not adequately controlled on SSA LAR therapy
      provides a novel treatment option for CSD. This model showed that providing
      access to this first-in-class oral agent would have a minimal budget impact to a
      US health plan.

PMID- 29175097
TI  - Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced
      Gastric Cancer Progressing After First-line Chemotherapy in Japan.
AB  - PURPOSE: The combination of paclitaxel + ramucirumab is a standard second-line
      treatment in patients with advanced gastric cancer. This therapy has been
      associated with increased median overall survival and progression-free survival
      compared with those with paclitaxel monotherapy. We evaluated the cost
      effectiveness of paclitaxel + ramucirumab combination therapy in patients with
      advanced gastric cancer, from the perspective of health care payers in Japan.
      METHODS: We constructed a Markov model to compare, over a time horizon of 3
      years, the costs and effectiveness of the combination of paclitaxel + ramucirumab
      and paclitaxel alone as second-line therapies for advanced gastric cancer in
      Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted
      (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (Y1 = US
      $17.79) according to the social insurance reimbursement schedule and drug tariff
      of the fee-for-service system in Japan. Model robustness was addressed through 1
      way and probabilistic sensitivity analyses. The costs and QALYs were discounted
      at a rate of 2% per year. The willingness-to-pay threshold was set at the World
      Health Organization's criterion of Y12 million, because no consensus exists
      regarding the threshold for acceptable cost per QALY ratios in Japan's health
      policy. FINDINGS: Paclitaxel + ramucirumab combination therapy was estimated to
      provide an additional 0.09 QALYs (0.10 LYs) at a cost of Y3,870,077, resulting in
      an incremental cost-effectiveness ratio of Y43,010,248/QALY. The incremental cost
      effectiveness ratio for the combination therapy was >Y12 million/QALY in all of
      the 1-way and probabilistic sensitivity analyses. IMPLICATIONS: Adding
      ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced
      gastric cancer is expected to provide a minimal incremental benefit at a high
      incremental cost per QALY. Based on our findings, adjustments in the price of
      ramucirumab, as well as improves in other clinical parameters such as survival
      time and adverse event in advanced gastric cancer therapy, are needed.

PMID- 29175098
TI  - Model-based tracking of the bones of the foot: A biplane fluoroscopy validation
      study.
AB  - Measuring foot kinematics using optical motion capture is technically challenging
      due to the depth of the talus, small bone size, and soft tissue artifact. We
      present a validation of our biplane X-ray system, demonstrating its accuracy in
      tracking the foot bones directly. Using an experimental linear/rotary stage we
      imaged pairs of tali, calcanei, and first metatarsals, with embedded beads,
      through 30 poses. Model- and bead-based algorithms were employed for semi
      automatic tracking. Translational and rotational poses were compared to the
      experimental stage (a reference standard) to determine registration performance.
      For each bone, 10 frames per pose were analyzed. Model-based: The resulting
      overall translational bias of the six bones was 0.058 mm with a precision of +/-
      0.049 mm. The overall rotational bias of the six bones was 0.42 degrees  with a
      precision of +/- 0.41 degrees . Bead-based: the overall translational bias was
      0.037 mm with a precision of +/- 0.032 mm and for rotation was 0.29 degrees  with
      a precision of +/- 0.26 degrees . We validated the accuracy of our system to
      determine the spatial position and orientation of isolated foot bones, including
      the talus, calcaneus, and first metatarsal over a range of quasi-static poses.
      Although the accuracy of dynamic motion was not assessed, use of an experimental
      stage establishes a reference standard.

PMID- 29175099
TI  - Ground-glass nodule segmentation in chest CT images using asymmetric multi-phase
      deformable model and pulmonary vessel removal.
AB  - We propose a ground-glass nodule (GGN) segmentation method that can separate
      solid component and ground-glass opacity (GGO) using an asymmetric multi-phase
      deformable model in chest CT images. First, initial solid component and GGO were
      extracted using intensity-based segmentation with histogram modeling. Second, the
      initial extracted regions were refined using an asymmetric multi-phase deformable
      model with modified energy functional and intensity-constrained averaging
      function. Finally, vessel-like structures are removed based on multi-scale shape
      analysis. In experiments, the segmentation accuracy of the entire GGN was
      evaluated using datasets from SNUH and LIDC/IDRI. The average DSC values of Seoul
      National University Hospital (SNUH) and Lung Image Database Consortium and Image
      Database Resource Initiative (LIDC/IDRI) were 0.85 +/- 0.05 and 0.78 +/- 0.07,
      respectively. The Pearson's correlation coefficient (r) between segmented volumes
      by the proposed method and manual segmentation was evaluated using SNUH dataset.
      The r of solid component, GGO, and entire GGN were 0.931, 0.875 and 0.907. Our
      experimental results show that the proposed method improves segmentation accuracy
      by applying the proposed asymmetric multiphase deformable model and pulmonary
      vessel removal.

PMID- 29175100
TI  - Computational modeling of drug transport across the in vitro cornea.
AB  - A novel quasi-3D (Q3D) modeling approach was developed to model networks of one
      dimensional structures like tubes and vessels common in human anatomy such as
      vascular and lymphatic systems, neural networks, and respiratory airways. Instead
      of a branching network of the same tissue type, this approach was extended to
      model an interconnected stack of different corneal tissue layers with membrane
      junction conditions assigned between the tissues. The multi-laminate structure of
      the cornea presents a unique barrier design and opportunity for investigation
      using Q3D modeling. A Q3D model of an in vitro rabbit cornea was created to
      simulate the drug transport across the cornea, accounting for transcellular and
      paracellular pathways of passive and convective drug transport as well as
      physicochemistry of lipophilic partitioning and protein binding. Lipophilic
      Rhodamine B and hydrophilic fluorescein were used as drug analogs. The model
      predictions for both hydrophilic and lipophilic tracers were able to match the
      experimental measurements along with the sharp discontinuities at the epithelium
      stroma and stroma-endothelium interfaces. This new modeling approach was
      successfully applied towards pharmacokinetic modeling for use in topical
      ophthalmic drug design.

PMID- 29175101
TI  - Direct modeling of blood flow through the vascular network of the germinal
      matrix.
AB  - A premature birth, before completion of the 32nd pregnancy week, increases the
      risk of cerebral hemorrhage. The cause of brain bleeding is very often the
      germinal matrix of the immature brain. The germinal matrix consists of richly
      vascularized neuroepithelial cells and is located over the lower part of the head
      of the caudate nucleus. By 32-36 gestation weeks, the germinal matrix essentially
      disappears so that its hemorrhage is a disease of premature infants. The aim of
      this paper consists in developing a model of the brain vascular network and
      computing the pressure distribution in the germinal matrix, particularly near
      arterioles and venules, where cerebral hemorrhage may occur. Capillary networks
      consisting of several millions of vessels are directly simulated in the present
      study.

PMID- 29175102
TI  - Altered lipid properties of the stratum corneum in Canine Atopic Dermatitis.
AB  - Skin barrier disruption plays a role in the pathogenesis of atopic dermatitis
      (AD) in humans. However, little is known about skin barrier (dys-) function in
      Canine Atopic Dermatitis. The properties of lipids located in the outermost layer
      of the skin, the stratum corneum (SC) are considered to be important for the
      barrier. In the present study the lipid composition and lipid organization of the
      SC of AD dogs and control dogs were examined. The lipid composition of lesional
      AD skin as compared to control skin, showed a reduced free fatty acid level and a
      decreased ratio of ceramide[NS] C44/C34, in which C44 and C34 are the total
      numbers of carbon atoms of the sphingosine (S) and non-hydroxy (N) acyl chains.
      As a consequence of the observed changes in lipid composition in AD lesional skin
      the lamellar organization of lipids altered and a shift from orthorhombic to
      hexagonal lipid packing was monitored. Simultaneously an increased conformational
      disordering occurred. These changes are expected to compromise the integrity of
      the skin barrier. The C44/C34 chain length ratio of ceramide[NS] also showed a
      decreasing nonlinear relationship with the AD severity score (CADESI). Taken
      together, canine atopic skin showed alterations in SC lipid properties, similar
      to the changes observed in atopic dermatitis in humans, that correlated with a
      disruption of the skin barrier. Hence lipids play an important role in the
      pathogenesis of Canine Atopic Dermatitis.

PMID- 29175103
TI  - Antioxidant activity of hydroxytyrosyl esters studied in liposome models.
AB  - The properties and the antioxidant activity of a series of hydroxytyrosyl esters
      having different carbon chain lengths (C4, C8, C12 and C18) have been measured in
      phosphatidylcholine model membrane (liposomes) using specific probes for the
      bilayer and liposome lumen microenvironment, i.e., 1,6-diphenyl-1,3,5-hexatriene
      (DPH) and 2',7'-dichlorodihydrofluorescein (H2DCF), respectively. Antioxidants
      self-assembly and their interaction with liposomes has been evaluated by light
      scattering, fluorescence, turbidimetry, gel filtration chromatography and
      microfiltration measurements, allowing the determination of critical aggregation
      concentration, bound fraction, capacity of crossing the lipid bilayer. The
      distribution of hydroxytyrosyl long chain esters has been proved to depend quite
      specifically on their lipophilic chain length, and this turns to have deep
      effects on their antioxidant behaviour. Shedding new light on the cut off effect
      and antioxidant behaviour of phenolipids, this study also put forward the
      relevance of cell-free liposome-based cellular models, like giant liposomes, for
      further characterization of analogous systems.

PMID- 29175104
TI  - Cramps frequency and severity are correlated with small and large nerve fiber
      measures in type 1 diabetes.
AB  - OBJECTIVES: To explore the correlations between different muscle cramp
      characteristics including cramp frequency and severity and clinical and large and
      small nerve fiber measures in patients with diabetes type 1 (DM 1) and 2 (DM 2).
      METHODS: Prospective cross sectional study of healthy controls and patients with
      DM 1 and DM 2 recruited between April 2009 and November 2012. Participants
      underwent clinical evaluation and large and small nerve fiber studies, and the
      frequency and correlations of muscle cramps were explored. RESULTS: 37 controls,
      51 patients with DM 1, and 69 patients with DM 2 were studied. Muscle cramps were
      the most frequent symptom captured by the Toronto Clinical Neuropathy Score
      (TCNS) in all groups, up to 78% in patients with DM 2. In patients with DM 1, but
      not DM 2, muscle cramp frequency and severity were correlated with clinical
      (TCNS) and both large (electrophysiology and vibration perception thresholds) and
      small nerve fiber measures. CONCLUSIONS: Muscle cramps are frequent in diabetes
      and are correlated with clinical and both small and large nerve fiber measures in
      DM 1, suggesting that their origin and propagation might extend beyond the motor
      nerve. SIGNIFICANCE: Muscle cramps correlate with nerve fiber measures in DM 1.

PMID- 29175105
TI  - Re-evaluating the role of FOXOs in cancer.
AB  - FOXO transcription factors are negatively regulated by the PI3K-PKB/AKT signaling
      pathway and have been mainly considered to be tumor suppressors due to their
      inhibitory effect on cancer cell growth and survival. However, FOXOs can also
      support tumor development and progression by maintaining cellular homeostasis,
      facilitating metastasis and inducing therapy resistance. In agreement with these
      opposing views on the role of FOXOs in cancer, studies using FOXO levels or
      activity as prognostic markers for cancer patient disease progression and
      survival came to contradicting results. While it is clear that FOXOs are involved
      in various aspects of cancer, it is debatable whether FOXOs function as tumor
      suppressors or supporters, or may be both depending on the context. In this
      review, we describe the role of FOXOs in signaling pathways and processes
      relevant to cancer and evaluate recent advances in understanding the role of
      FOXOs in cancer. Based on recent insights it becomes clear that FOXOs may not be
      classical tumor suppressors and that targeting FOXO activity might hold promise
      in cancer therapy.

PMID- 29175106
TI  - Comprehensive pancancer genomic analysis reveals (RTK)-RAS-RAF-MEK as a key
      dysregulated pathway in cancer: Its clinical implications.
AB  - Recent advances in Next Generation Sequencing (NGS) have provided remarkable
      insights into the genomic characteristics of human cancers that have spurred a
      revolution in the field of oncology. The mitogen-activated protein kinase pathway
      (MAPK) and its activating cell receptor, the receptor tyrosine kinases (RTKs),
      which together encompass the (RTK)-RAS-RAF-MEK-ERK axis, are central to
      oncogenesis. A pan-cancer genomics analysis presented in this review is made
      possible by large collaborative projects, including The Cancer Genome Atlas
      (TCGA), the International Cancer Genome Consortium (ICGC), and others. Landmark
      studies contributing to these projects have revealed alterations in cell
      signaling cascades that vary between cancer types and within tumors themselves.
      We review several of these studies in major tumor types to highlight recent
      advances in our understanding of the role of (RTK)-RAS-RAF alterations in cancer.
      Further studies are needed to increase the statistical power to detect clinically
      relevant low-frequency mutations, in addition to the known (RTK)-RAS-RAF pathway
      alterations, and to refine the resolution of the genomic landscape that defines
      these cancer mutations. The (RTK)-RAS-RAF-MEK-ERK mutation status, and their
      prognostic value, are also examined and correlated with clinical phenotypes.
      Treatments targeting various components of this pathway are ongoing, and are
      often effective initially in defined subgroups of patients. However, resistance
      to these agents can develop through adaptive mechanisms. With our steady increase
      in understanding the molecular biology of cancer, ongoing evaluation and
      monitoring through genomic analysis will continue to provide important
      information to the clinician in the context of treatment selection, response,
      resistance and outcomes.

PMID- 29175108
TI  - Nonstructural protein 2A modulates replication and virulence of enterovirus 71.
AB  - Enterovirus 71 (EV71) can cause hand, foot, and mouth disease in children, and
      severe infections can induce neurological complications and even death. However,
      the pathogenesis of EV71 remains unknown. The 2A proteinase (2Apro) of EV71 plays
      an important role in segmenting the precursor polyprotein during viral
      replication, inhibiting host protein synthesis, and evading innate immunity. This
      study was to determine the function of EV71 2Apro in replication and virulence. A
      chimeric strain (SDLY 107-2A-1) was recombined by replacing 2Apro of a severe
      strain (SDLY107) with that of a mild strain (SDLY1) based on an infectious cDNA
      clone. The replication kinetics of the chimeric strain in vitro and in vivo were
      determined by qRT-PCR, which showed that the chimeric strain replicated slower
      and generated less viral RNA than the severe strain. The pathological change and
      viral load of chimeric strain infected mice were intermediate between severe
      strain infected mice and mild strain infected mice. Cellular cytotoxicity assays
      revealed that 2Apro was associated with the neurotoxicity of EV71.
      Histopathological and immunohistochemical assays detected tissue pathological
      damage in the lungs, muscles, brain, and intestinal tissues. Together, these
      results suggest that 2Apro modulates replication and virulence of EV71. This
      provides a theoretical basis for virulence determination of EV71.

PMID- 29175109
TI  - Comments on "Direct quantitative measurement of the kinetics of HLA-specific
      antibody interactions with isolated HLA proteins".

PMID- 29175111
TI  - Metabolomics Approach to Male Lower Urinary Tract Symptoms: Identification of
      Possible Biomarkers and Potential Targets for New Treatments.
AB  - PURPOSE: We identified metabolites using a metabolomics approach and investigated
      the association between these metabolites and lower urinary tract symptoms.
      MATERIALS AND METHODS: We used a 24-hour bladder diary and I-PSS (International
      Prostate Symptom Score) to assess micturition behavior and lower urinary tract
      symptoms in 58 male patients without apparent neurological disease. Lower urinary
      tract symptoms were defined as a total I-PSS score of 8 or greater. Patients with
      a score of 7 or less were placed in the control group. A comprehensive study of
      plasma metabolites was also performed by capillary electrophoresis time-of-flight
      mass spectrometry. Metabolites were compared between the lower urinary tract
      symptoms and control groups using the Mann-Whitney U test. Biomarkers of male
      lower urinary tract symptoms from the metabolites were analyzed using
      multivariable logistic regression analysis to determine the OR. RESULTS: Of the
      58 men 32 were in the lower urinary tract symptoms group and the remaining 26
      were in the control group. The 24-hour bladder diary showed that nocturnal urine
      volume, 24-hour micturition frequency, nocturnal micturition frequency and the
      nocturia index were significantly higher in the lower urinary tract symptoms
      group. Metabolomics analysis identified 60 metabolites from patient plasma.
      Multivariate analysis revealed that increased glutamate and decreased arginine,
      asparagine and inosine monophosphate were significantly associated with lower
      urinary tract symptoms in males. Decreases in citrulline and glutamine could also
      be associated with male lower urinary tract symptoms. CONCLUSIONS: Male lower
      urinary tract symptoms may develop due to abnormal metabolic processes in some
      pathways. Potential new treatments for lower urinary tract symptoms can be
      developed by identifying changes in the amino acid profiles.

PMID- 29175110
TI  - Preclinical and clinical studies for transplant tolerance via the mixed chimerism
      approach.
AB  - Based upon observations in murine models, we have developed protocols to induce
      renal allograft tolerance by combined kidney and bone marrow transplantation
      (CKBMT) in non-human primates (NHP) and in humans. Induction of persistent mixed
      chimerism has proved to be extremely difficult in major histocompatibility
      complex (MHC)-mismatched primates, with detectable chimerism typically
      disappearing within 30-60 days. Nevertheless, in MHC mismatched NHP, long-term
      immunosuppression-free renal allograft survival has been achieved reproducibly,
      using a non-myeloablative conditioning approach that has also been successfully
      extended to human kidney transplant recipients. CKBMT has also been applied to
      the patients with end stage renal disease with hematologic malignancies. Renal
      allograft tolerance and long-term remission of myeloma have been achieved by
      transient mixed or persistent full chimerism. This review summarizes the current
      status of preclinical and clinical studies for renal and non-renal allograft
      tolerance induction by CKBMT. Improving the consistency of tolerance induction
      with less morbidity, extending this approach to deceased donor transplantation
      and inducing tolerance of non-renal transplants, are critical next steps for
      bringing this strategy to a wider range of clinical applications.

PMID- 29175107
TI  - Viruses of archaea: Structural, functional, environmental and evolutionary
      genomics.
AB  - Viruses of archaea represent one of the most enigmatic parts of the virosphere.
      Most of the characterized archaeal viruses infect extremophilic hosts and display
      remarkable diversity of virion morphotypes, many of which have never been
      observed among viruses of bacteria or eukaryotes. The uniqueness of the virion
      morphologies is matched by the distinctiveness of the genomes of these viruses,
      with ~75% of genes encoding unique proteins, refractory to functional annotation
      based on sequence analyses. In this review, we summarize the state-of-the-art
      knowledge on various aspects of archaeal virus genomics. First, we outline how
      structural and functional genomics efforts provided valuable insights into the
      functions of viral proteins and revealed intricate details of the archaeal virus
      host interactions. We then highlight recent metagenomics studies, which provided
      a glimpse at the diversity of uncultivated viruses associated with the ubiquitous
      archaea in the oceans, including Thaumarchaeota, Marine Group II Euryarchaeota,
      and others. These findings, combined with the recent discovery that archaeal
      viruses mediate a rapid turnover of thaumarchaea in the deep sea ecosystems,
      illuminate the prominent role of these viruses in the biosphere. Finally, we
      discuss the origins and evolution of archaeal viruses and emphasize the
      evolutionary relationships between viruses and non-viral mobile genetic elements.
      Further exploration of the archaeal virus diversity as well as functional studies
      on diverse virus-host systems are bound to uncover novel, unexpected facets of
      the archaeal virome.

PMID- 29175112
TI  - Chalcones as putative hepatoprotective agents: Preclinical evidence and molecular
      mechanisms.
AB  - Chalcones form an important group of natural compounds and flavonoid precursors
      which are abundant in fruits, vegetables, and edible plants. These compounds have
      many beneficial properties including anti-inflammatory, anti-microbial,
      antioxidant, anti-cancer, anti-amyloid, anti-diabetic, anti-obesity,
      hypolipidemic, and cytoprotective. Chalcone derivatives have protective effects
      on the liver in nonalcoholic fatty liver disease, alcoholic fatty liver, drug-
      and toxicant-induced liver injury, and liver cancer through several mechanisms.
      Chalcones improve adipocytes function and adiponectin secretion. They inhibit
      triglyceride synthesis, activating factors of hepatic stellate cells and
      extracellular matrix deposition and also elevate fatty acid oxidation. These
      effects of chalcones lead to liver injury improvement. In conclusion, chalcones
      with antioxidant, anti-fibrotic, and anti-inflammatory properties decrease liver
      injury markers and histological abnormality in liver injury.

PMID- 29175113
TI  - Molecular adjuvants that modulate regulatory T cell function in vaccination: A
      critical appraisal.
AB  - Adjuvants are substances used to enhance the efficacy of vaccines. They influence
      the magnitude and alter the quality of the adaptive immune response to vaccine
      antigens by amplifying or modulating different signals involved in the innate
      immune response. The majority of known adjuvants have been empirically
      identified. The limited immunogenicity of new vaccine antigens and the need for
      safer vaccines have increased the importance of identifying single, well-defined
      adjuvants with known cellular and molecular mechanisms for rational vaccine
      design. Depletion or functional inhibition of CD4+CD25+FoxP3+ regulatory T cells
      (Tregs) by molecular adjuvants has become an emergent approach in this field.
      Different successful results have been obtained for specific vaccines, but there
      are still unresolved issues such as the risk of autoimmune disease induction, the
      involvement of cells other than Tregs and optimization for different conditions.
      This work provides a comprehensive analysis of current approaches to inhibit
      Tregs with molecular adjuvants for vaccine improvement, highlights the progress
      being made, and describes ongoing challenges.

PMID- 29175114
TI  - Phytochemical portfolio and anticancer activity of Murraya koenigii and its
      primary active component, mahanine.
AB  - Murraya koenigii, a plant belonging to the Rutaceae family is widely distributed
      in Eastern-Asia and its medicinal properties are well documented in Ayurveda, the
      traditional Indian system of medicine. Through systematic research and
      pharmacological evaluation of different parts of the plant extracts has been
      shown to possess antiviral, anti-inflammatory, antioxidant, antidiabetic,
      antidiarrhoeal, antileishmanial, and antitumor activity. In the plant extracts,
      carbazole alkaloid, mahanine has been identified as the principle bioactive
      component among several other chemical constituents. Scientific evidence derived
      not only from in vitro cellular experiments but also from in vivo studies in
      various cancer models is accumulating for the pronounced anticancer effects of
      mahanine. The primary objective of this review is to summarize research data on
      cytotoxic chemical constituents present in different parts of Murraya koenigii
      and the anticancer activity of mahanine along with the recent understanding on
      the mechanism of its action in diverse cancer models. The information on its
      bioavailability and the toxicity generated from the recent studies have also been
      incorporated in the review.

PMID- 29175115
TI  - Comparison of Four PD-L1 Immunohistochemical Assays in Lung Cancer.
AB  - INTRODUCTION: Four different programmed death ligand 1 immunohistochemical assays
      are approved or in development as companion or complementary diagnostics to
      different immunotherapeutic agents in lung carcinoma. We sought to determine
      whether these assays are technically equivalent and whether one antibody can be
      used on an alternate staining platform. METHODS: Serial sections of tissue
      microarrays constructed from 368 cases of resected lung cancer were stained for
      22C3 and 28-8 on the Dako Link 48 platform (Dako, Carpinteria, Ca) and for SP142
      and SP263 on the Ventana Benchmark Ultra platform (Ventana Medical Systems,
      Tucson, AZ) strictly as per product insert. A protocol was developed to use the
      22C3 antibody on the Ventana Benchmark Ultra platform. RESULTS: Differences in
      mean tumor cell and immune cell staining were observed between the four assays (p
      < 0.001). Differences between 22C3 and 28-8 were not statistically significant.
      Concordance of tumor cell scores was good (intraclass correlation coefficient
      [ICC] = 0.674), particularly when SP142 was excluded as an outlier (ICC = 0.755).
      The highest concordance was seen between 22C3 and 28-8 (ICC = 0.812). Concordance
      was poor for immune cell staining (ICC = 0.212). When dichotomized according to
      clinically relevant cutoffs, pairwise comparisons showed poor to moderate
      concordance (kappa = 0.196-0.578), with positive percent agreement ranging from
      15.1% to 90.0%. The 22C3 antibody performed comparably on the Dako Link 48
      platform and the alternate Ventana Benchmark Ultra platform (ICC = 0.921, kappa =
      0.897). CONCLUSIONS: Concordance between the four programmed death ligand 1
      immunohistochemical assays when performed and scored as intended show that apart
      from 28-8 and 22C3, they cannot be used interchangeably in clinical practice. A
      protocol was successfully developed to use 22C3 on an alternate platform, which
      may help to overcome some barriers to implementation.

PMID- 29175116
TI  - Current and Emergent Therapy Options for Advanced Squamous Cell Lung Cancer.
AB  - Squamous cell lung cancer (SqCLC) is a distinct histologic subtype of NSCLC that
      is challenging to treat because of specific clinicopathologic characteristics,
      which include older age, advanced disease at diagnosis, comorbid diseases, and
      the central location of tumors. These characteristics have a bearing on treatment
      outcomes in advanced SqCLC, resulting in a median survival approximately 30%
      shorter than for patients with other NSCLC subtypes. In the context of the
      specific features of SqCLC, we review challenges of treating SqCLC and the
      current guideline-recommended treatments for advanced (metastatic) SqCLC in
      different patient subpopulations. We also evaluate recently approved treatment
      options, including necitumumab, afatinib, nivolumab, pembrolizumab, and
      atezolizumab; discuss the survival benefits associated with each agent in the
      advanced SqCLC population; and propose a treatment algorithm incorporating these
      agents for this challenging-to-treat disease. Lastly, we review the preliminary
      clinical evidence for immunotherapy agents in development for advanced NSCLC.

PMID- 29175117
TI  - Rossete-like deposits of uncertain etiology on the intraocular lens.

PMID- 29175118
TI  - Metformin and vitamin B12-What's missing from this picture?

PMID- 29175119
TI  - Circulating levels of Hsp27 in microvascular complications of diabetes: Prospects
      as a biomarker of diabetic nephropathy.
AB  - AIM: Heat shock protein 27 (Hsp27) is a small heat shock protein known to protect
      the cells from apoptosis under stress. In the present study, we determined the
      plasma Hsp27 levels in type 2 diabetes subjects without and with microvascular
      complications- diabetic retinopathy (DRe), diabetic nephropathy (DNe), and
      diabetic neuropathy (DNu) to understand if it could serve as a marker for these
      complications. METHODS: This is a hospital-based case-control study with 754
      subjects including 247 controls, 195 subjects with diabetes, 123 with DRe, 80
      with DNe and 109 with DNu. Plasma Hsp27 levels were measured by ELISA. RESULTS:
      The mean plasma Hsp27 was higher in the DNe group (631.5+/-355.2) compared to the
      control (496.55+/-308.54), diabetes (523.41+/-371.01), DRe (494.60+/-391.48) and
      DNu (455.21+/-319.74) groups with a p-value of 0.018. Receiver operating
      characteristic (ROC) curve analysis of Hsp27 in DNe group showed an area under
      the curve (AUC) of 0.617. Spearman correlation analysis shows a positive
      correlation of plasma Hsp27 with serum creatinine (p=0.053, r-value 0.083).
      Gender, age and BMI did not affect the plasma Hsp27 levels. CONCLUSION: The
      plasma Hsp27 levels in the DNe group are higher compared to the control and other
      complications, thereby it could be explored to be used as a potential biomarker
      of DNe.

PMID- 29175120
TI  - Urinary miRNA-377 and miRNA-216a as biomarkers of nephropathy and subclinical
      atherosclerotic risk in pediatric patients with type 1 diabetes.
AB  - BACKGROUND: Urinary microRNAs (miRNAs) play a role in the pathogenesis of chronic
      kidney disease (CKD). AIM: To identify the expression of urinary miR-377 and miR
      216a in 50 children and adolescents with type 1 diabetes (T1DM) compared with 50
      healthy controls and assess their relation to the degree of albuminuria, glycemic
      control and carotid intimal thickness (CIMT) as an index of atherosclerosis.
      METHODS: Diabetic subjects were divided into normoalbuminuric and
      microalbuminuric groups according to urinary albumin creatinine ration (UACR).
      Urinary miRNAs were assessed using real time polymerase chain reaction. CIMT was
      measured using high resolution carotid ultrasound. RESULTS: The expression of
      urinary miR-377 was significantly higher in patients with microalbumiuria
      (median, 3.8) compared with 2.65 and 0.98 in normoalbuminic patients and healthy
      controls, respectively (p<0.05). Urinary miR-216a was significantly lower in all
      patients with type 1 diabetes and the lowest levels were among the
      microalbumiuric group. Significant positive correlations were found between
      urinary miR-377 and HbA1C, UACR and CIMT while urinary miR-216a was negatively
      correlated to these variables. CONCLUSIONS: Urinary miR-377 and miR-216a can be
      considered early biomarkers of nephropathy in pediatric type 1 diabetes. Their
      correlation with CIMT provides insights on the subclinical atherosclerotic
      process that occurs in diabetic nephropathy.

PMID- 29175121
TI  - Elevated unmethylated and methylated insulin DNA are unique markers of A+beta+
      ketosis prone diabetes.
AB  - A+beta+ ketosis prone diabetes (KPD) is associated with slowly progressive
      autoimmune beta cell destruction. Plasma unmethylated and methylated insulin DNA
      (biomarkers of ongoing beta cell damage and systemic inflammation, respectively)
      were elevated in A+beta+ KPD compared to all other KPD subgroups.

PMID- 29175122
TI  - Effect of saturation in phospholipid/fatty acid monolayers on interaction with
      amyloid beta peptide.
AB  - The effect of the saturation of fatty acid (FA) in 1,2-dimyristoyl-sn-glycero-3
      phosphocoline (DMPC)/FA membrane on the interaction between lipid membrane and
      amyloid beta monomer was investigated by using the Langmuir monolayer technique.
      The surface pressure (Pi)-mean molecular area (A) isotherms and fluorescent
      measurements reveal that DMPC and octadecanoic acid (stearic acid, SA) molecules
      were somewhat miscible in the mixed membrane, which was maintained to homogeneous
      gel phase by enhance of the intermolecular hydrophobic interactions because of
      the all trans acyl chains. On the other hand, DMPC and 9Z,12Z-octadecadienoic
      acid (linoleic acid, LA) molecules were considered to be well miscible in the
      mixed membrane, where the membrane partially transferred from gel phase to liquid
      crystalline phase. The Pi-A isotherms of the monolayers on amyloid beta-peptide
      (Abeta) solution indicated that Abeta monomers tend to be inserted into the
      saturated acyl chain region of monolayers at low surface pressure and that the
      Abeta monomers were then extruded from the monolayer at higher surface pressure.
      It was observed that behaviors of Abeta monomers at higher surface pressure
      depended on membrane microstructures. In the DMPC/SA monolayers, Abeta aggregated
      and then was extruded from monolayers at about 20 mN m-1 of surface pressure
      irrespective of the SA proportion. On the other hand, in the DMPC/LA monolayers,
      Abeta, which favors to interact with DMPC, is dispersed in the monolayer even at
      high surface pressure because DMPC and LA molecules were well miscible in the
      monolayer.

PMID- 29175123
TI  - Characterization and application of a novel nicotinamide mononucleotide
      adenylyltransferase from Thermus thermophilus HB8.
AB  - Herein, we describe a novel enzymatic cycling method to measure nicotinamide
      mononucleotide (NMN) or nicotinic acid mononucleotide (NaMN), which are
      precursors of NAD biosynthesis. A gene encoding an NMN adenylyltransferase
      (NMNAT, EC 2.7.7.1) homologue was identified in Thermus thermophilus HB8. The
      gene from T. thermophilus (TtNMNAT) was engineered for expression in Escherichia
      coli and the recombinant enzyme found to be stable, retaining full activity after
      incubation for 45 min at 70 degrees C. The Km values for NMN and ATP were
      calculated to be 0.263 and 1.27 mM, respectively, with a Vmax value of 60.3
      MUmoL/min/mg. TtNMNAT was successfully applied to the colorimetric NMN or NaMN
      assays, which employed (i) adenylation of NMN to NAD by TtNMNAT or adenylation of
      NaMN to deamido-NAD (NaAD) by TtNMNAT followed by amidation of NaAD to NAD by NAD
      synthetase (NADS, EC 6.3.1.5) and (ii) an NAD cycling reaction using 12alpha
      hydroxysteroid dehydrogenase (12alpha-HSD, EC 1.1.1.176) and diaphorase (DI, EC
      1.6.99.3) to accumulate reduced WST-8. This enzymatic cycling method enabled
      detection of 0.5 MUM (12.2 nM in the reaction mixture) NMN or NaMN in an
      automatic clinical analyzer.

PMID- 29175124
TI  - Enhanced cell-surface display of a heterologous protein using SED1 anchoring
      system in SED1-disrupted Saccharomyces cerevisiae strain.
AB  - Yeast displaying enzymes on the cell surface are used for developing whole-cell
      biocatalysts. High enzyme activity on the cell surface is required in certain
      applications such as direct ethanol production from lignocellulosic materials.
      However, the cell surface enzyme activity is limited by several factors, one of
      which is the protein amount of the yeast cell wall. In this study, we attempted
      to improve the incorporation capacity of a displayed heterologous enzyme by
      disrupting a native cell-wall protein. beta-Glucosidase (BGL1) from Aspergillus
      aculeatus was fused with Saccharomyces cerevisiae Sed1 and displayed on the cell
      surface of S. cerevisiae BY4741 strain and its SED1 disruptant. Sed1 is one of
      the most abundant stationary phase yeast cell wall protein. A time course
      analysis revealed that BGL1 activity of the control strain reached saturation
      after 48 h of cultivation. In contrast, the BGL1 activity of the SED1 disruptant
      increased until 72 h of cultivation and was 22% higher than that of the control
      strain. We also performed relative quantification of cell wall proteins of these
      strains by nanoscale ultra pressure liquid chromatography electrospray ionization
      quadrupole time-of-flight tandem mass spectrometry (nano-UPLC-MSE). The amount of
      the cell wall-associated BGL1 per unit dry cell-weight of the SED1 disruptant was
      19% higher than that of the control strain. These results suggested that the
      incorporation capacity of the cell wall for BGL1 was increased by disruption of
      SED1. Disruption of SED1 would be a promising approach for improving display
      efficiency of heterologous protein fused with Sed1.

PMID- 29175125
TI  - Changes in tetracycline partitioning and bacteria/phage-comediated ARGs in
      microplastic-contaminated greenhouse soil facilitated by sophorolipid.
AB  - The emerging mixed contamination of antibiotics and microplastics in greenhouse
      soil has made the control of antibiotic resistant gene (ARG) transmission a novel
      challenge. In this work, surfactant sophorolipid was applied to enhance the
      dissipation of tetracycline (TC) and tet genes in the presence of microplastics
      in greenhouse soil. During 49days of incubation, soil bacteria and phages were
      both found to be the crucial reservoirs of ARGs. Meanwhile, microplastic's
      presence significantly inhibited the dissipation of TC and ARGs in the soil.
      However, sophorolipid application was proved to outweigh the negative impact
      caused by microplastic existence, and lead to the highest dissipation of soil TC
      and ARGs. Significant positive correlation was detected between the dissipation
      rate of water-soluble and exchangeable TC content and bacteria/phage co-mediated
      ARG levels. This also held true between the two fractions of soil TC and the
      ratio of ARG level in the bacteria to that in the phages (BARGs/PARGs). The
      opposite impacts of microplastic presence and sophorolipid amendment on the
      TC/ARG dissipation found in this work provides new information for understanding
      ARG transmission between bacteria and phages in the mixed contaminated greenhouse
      soil.

PMID- 29175126
TI  - Immunolocalization of connective tissue growth factor, transforming growth factor
      beta1 and phosphorylated-SMAD2/3 during the postnatal tooth development and
      formation of junctional epithelium.
AB  - Connective tissue growth factor (CTGF) is a downstream mediator of transforming
      growth factor-beta 1 (TGF-beta1) and TGF-beta1-induced CTGF expression is
      regulated through SMAD pathway. However, there is no literature showing the
      expression of TGF-beta1-SMAD2/3-CTGF signaling pathway during postnatal tooth
      development and the formation of junctional epithelium (JE). Hence, we aimed to
      analyze the localization of TGF-beta1, CTGF and phosphorylated SMAD2/3 (p
      SMAD2/3) in the developing postnatal rat molars. Wistar rats were killed at
      postnatal (PN) 0.5, 3.5, 7, 14 and 21days and the upper jaws were processed for
      immunohistochemistry. At PN0.5 and PN3.5, weak staining for TGF-beta1 and CTGF
      was evident in preameloblasts (PA), while moderate to strong staining was seen in
      odontoblasts (OD), dental papilla (DPL), secretary ameloblasts (SA),
      preodontoblasts (PO) and polarized odontoblasts (PoO). There was no staining for
      p-SMAD2/3 in PA, SA, PO and PoO, although strong staining was localized in DPL.
      OD was initially moderately positive and then negative for p-SMAD2/3. At PN7,
      intense staining for TGF-beta1 and CTGF was observed in SA, OD, dental pulp (DP)
      and predentin respectively. p-SMAD2/3 was strongly expressed in DP and moderately
      expressed in SA and OD. At PN14 and PN21, both reduced enamel epithelium (REE)
      and JE showed a strong reaction for TGF-beta1 and CTGF. p-SMAD2/3 was intensely
      and weakly expressed in REE and JE respectively. These data demonstrate that the
      expression of CTGF, TGF-beta1 and p-SNAD2/3 is tissue-specific and stage
      specific, and indicate a regulatory role for a TGF-beta1-SMAD2/3-CTGF signaling
      pathway in amelogenesis, dentinogenesis and formation of JE.

PMID- 29175127
TI  - Retro-2 and its dihydroquinazolinone derivatives inhibit filovirus infection.
AB  - Members of the family Filoviridae cause severe, often fatal disease in humans,
      for which there are no approved vaccines and only a few experimental drugs tested
      in animal models. Retro-2, a small molecule that inhibits retrograde trafficking
      of bacterial and plant toxins inside host cells, has been demonstrated to be
      effective against a range of bacterial and virus pathogens, both in vitro and in
      animal models. Here, we demonstrated that Retro-2 and its derivatives, Retro-2.1
      and compound 25, blocked infection by Ebola virus and Marburg virus in vitro. We
      show that the derivatives were more potent inhibitors of infection as compared to
      the parent compound. Pseudotyped virus assays indicated that the compounds
      affected virus entry into cells while virus particle localization to Niemann-Pick
      C1-positive compartments showed that they acted at a late step in virus entry.
      Our work demonstrates a potential for Retro-type drugs to be developed into anti
      filoviral therapeutics.

PMID- 29175128
TI  - An evaluation of Chloroquine as a broad-acting antiviral against Hand, Foot and
      Mouth Disease.
AB  - A common childhood affliction of viral origin in young children and
      immunocompromised adults, the Hand, Foot and Mouth Disease (HFMD) has become a
      significant public health concern in the Asia-Pacific Region. Characterized by
      the appearance of vesiculopapular rashes on the hands, feet and mouth, the
      disease is generally mild and self-limiting. In a minority of cases, patients can
      develop neurological complications that could result in permanent morbidity or
      even fatality. In the absence of a specific antiviral for treatment, medical care
      is limited to supportive and symptomatic relief, presenting a need for more
      research into an effective antiviral to be used in the management of the disease.
      In this study, we evaluated the efficacy of chloroquine, a FDA-approved
      lysosomotropic agent, against several serotypes of HFMD-associated enteroviruses,
      including EV-A71, in reducing infectious virus production. We have also evaluated
      chloroquine in a murine model of EV-A71 infection to ascertain its antiviral
      efficacy in vivo. The results suggest that chloroquine could be a broad-acting
      antiviral effective against HFMD-associated enteroviruses.

PMID- 29175129
TI  - Vitamin D metabolic loci and vitamin D status in Black and White pregnant women.
AB  - BACKGROUND: Several candidate genes and genome wide association studies have
      reported significant associations between vitamin D metabolism genes and 25
      hydroxyvitamin D. Few studies have examined these relationships in pregnancy.
      OBJECTIVE: We evaluated the relationship between maternal allelic variants in
      three vitamin D metabolism genes and 25-hydroxyvitamin D (25(OH)D) concentration
      in pregnancy. STUDY DESIGN: In two case-control studies, samples were drawn from
      women who delivered at Magee Womens Hospital in Pittsburgh, PA from 1999 to 2010
      and twelve recruiting sites across the United States from 1959 to 65. For 882
      Black and 1796 White pregnant women from these studies, 25(OH)D concentration was
      measured and single nucleotide polymorphisms (SNPs) were genotyped 50 kilobases
      up- and down-stream in three genes (VDR, GC, and CYP27B1). Using multivariable
      linear regression, we estimated the associations between allelic variation of
      each locus and log-transformed 25(OH)D concentration separately by race and study
      group. Meta-analysis was used to estimate the association across the four groups
      for each SNP. RESULTS: Minor alleles of several variants in VDR, GC, and CYP27B1
      were associated with differences in log-transformed 25(OH)D concentration
      compared to the corresponding major alleles [beta, 95% confidence intervals
      (CI)]. The meta-analysis confirmed the associations for differences in log
      transformed 25(OH)D by allelic loci for one intron VDR variant [rs2853559 0.08
      (0.02, 0.13), p<0.01] and a variant in the GC flanking region [rs13150174: 0.04
      (0.02, 0.07), p<0.01], and a GC missense mutation [rs7041 0.05 (0.01, 0.09),
      p<0.01]. The meta-analysis also revealed possible associations for SNPs in
      linkage disequilibrium with variants in the VDR 3-prime untranslated region,
      another GC missense variant (rs4588), and a variant of the 3-prime untranslated
      region of CYP27B1. CONCLUSION: We observed associations between VDR, GC, and
      CYP27B1 variants and maternal 25-hydroxyvitamin D concentration. Our results
      provide additional support for a possible role of genetic variation in vitamin D
      metabolism genes on vitamin D status during pregnancy.

PMID- 29175130
TI  - Urinary incontinence is strongly associated with depression in middle-aged and
      older Korean women: Data from the Korean longitudinal study of ageing.
AB  - OBJECTIVE: To investigate the relationship between urinary incontinence (UI) and
      depression in middle-aged and older Korean women. STUDY DESIGN: A total of 1116
      participants diagnosed with UI among 7486 respondents were included in this
      study, using data from a well-established survey that investigated a nationally
      representative population: the Korean Longitudinal Study of Ageing (KLoSA).
      Computer-assisted personal interviewing was used to assess the status of UI and
      depression. Depression was assessed using the 10-item Center for Epidemiological
      Studies-Depression (CES-D 10) scale. Odds ratios (ORs) and 95% confidence
      intervals (95% CIs) for depression were adjusted for age, household income level,
      marital status, education level, working status, smoking behavior, alcohol
      drinking behavior, exercise level, residence, and accompanying chronic diseases.
      RESULTS: The proportion of patients with depression was significantly higher
      among women with UI (9.1%) than among women without UI (6.3%) (P<0.0001). The
      depression scores became worse with worsening UI symptoms (OR of better vs. same
      vs. worse, 1.00 vs. 1.51 vs. 2.15, respectively; P for trend=0.0001), with an
      increased number of days experiencing UI during the prior month during the 2
      years of the panel study period (OR of none vs. 1<=days<=10days vs. 10days<were
      1.00 vs. 2.15 vs. 4.36; P for trend=0.003). CONCLUSIONS: Inadequately controlled
      and frequent UI is strongly associated with depression in middle-aged and older
      Korean women. The management of worsening UI may be of value as part of the
      assessment and management of depression.

PMID- 29175131
TI  - Sacrocolpopexy with polyvinylidene fluoride mesh for pelvic organ prolapse: Mid
      term comparative outcomes with polypropylene mesh.
AB  - OBJECTIVE: The aim of this study was to compare the surgical, anatomical, and
      functional outcomes of sacrocolpopexy (SCP) using polyvinylidene fluoride (PVDF)
      mesh versus SCP using the standard polypropylene (PP) mesh. STUDY DESIGN: This
      was a retrospective single centre case-control study including female patients
      who underwent laparoscopic or abdominal SCP for POP with either PP (Cousin
      Biotech(r)) or PVDF (DynaMesh(r)-PRS) mesh between March 2005 and May 2015.
      Anatomical outcomes were assessed by the Pelvic Organ Prolapse Quantification
      (POP-Q) system. Functional outcomes included voiding and storage urinary symptoms
      (VS and SS, respectively), urgency and stress urinary incontinence (UUI and SUI)
      and sexual dysfunction (SD). Symptoms and their impact on patients' quality of
      life (QoL) were assessed using validated questionnaires as Incontinence Impact
      Questionnaire (IIQ-7), Urinary Distress Inventory (UDI-6) and Female Sexual
      Function Index (FSFI). Global patient perception of improvement (PGI-I
      questionnaire) and mesh erosion rates were also recorded. RESULTS: Of the 166
      patients enrolled, 136 could be included in the analysis: 73 in the PP group and
      63 in the PVDF group. The mean follow-up was 94+/- 17.31 months for the PP and
      25.6+/- 13.8 months for the PVDF group. There were no statistically significant
      differences in patient demographics and preoperative clinical characteristics.
      Postoperative anatomical correction were not significantly different between the
      two groups. The PVDF group showed superior results in term of storage symptoms
      (PVDF=0% versus PP=8.2%; p=0.02) and lower rate of sexual dysfunction (PVDF=0%
      versus PP=16,4%; p=0.001). Only 1 patient in PP group and 2 in PVDF group
      (p=0.47) presented a mesh exposure. There was no statistical difference in PGI-I
      scores (PP=1.5+/-1.0 vs PVDF=1.8+/-0.5; p=0.40). CONCLUSIONS: Our findings
      suggest that both meshes can be safely and effectively used with good anatomical
      outcomes. Interestingly, PVDF use was associated with significantly less storage
      symptoms and sexual dysfunction.

PMID- 29175132
TI  - Dutch women's attitudes towards hysterectomy and uterus preservation in surgical
      treatment of pelvic organ prolapse.
AB  - OBJECTIVE: To investigate Dutch women's attitudes and preferences towards
      hysterectomy or uterus preservation in surgical treatment of pelvic organ
      prolapse. STUDY DESIGN: Women's attitude was assessed by a structured
      questionnaire in one university hospital and one non-university teaching hospital
      in the Netherlands. Between December 2013 and November 2014, 102 women referred
      with prolapse complaints, without previous prolapse surgery, responded to the
      questionnaire received by mail prior to gynaecological consultation. Main outcome
      was the preference for uterus preserving surgery versus hysterectomy. Furthermore
      we studied the impact of uterus preservation and hysterectomy on body image and
      sexual function and the importance of treatment success, risk of urinary
      incontinence after surgery, complication risk, recovery time, length of hospital
      stay, costs and the risk of developing endometrial cancer. RESULTS: Assuming that
      functional and anatomical outcomes after hysterectomy and uterus preserving
      surgery were equal, more women expressed preference for uterus preservation (43%,
      44 out of 102 women) compared to hysterectomy (27%, 27 out of 102 women). The
      majority of women expected a similar improvement in sexuality and body image
      after the two treatment modalities. Treatment success, risk for urinary
      incontinence after surgery and complication risk were the most important factors.
      Taken the future risk of endometrial cancer into account, 18% of the women
      preferred hysterectomy because of this risk. CONCLUSIONS: This study demonstrated
      that women referred with prolapse complaints have a preference for uterus
      preservation in case outcomes after both interventions are expected to be equal.
      The majority of women expected that body image and sexual function would equally
      improve after both interventions.

PMID- 29175133
TI  - Rectus femoris branch: An alternative blood supply for a distally based
      anterolateral thigh flap.
AB  - Successful raising of a distally based anterolateral thigh (dALT) flap mainly
      depends on a well-developed lateral circumflex femoral artery (LCFA) descending
      branch and an intact vascular connection between the descending branch and the
      vascular network of the knee. However, in some clinical scenarios, the descending
      branch is hypoplastic or the vascular connection of the knee is compromised. We
      present six cases of using dALT flaps in soft tissue defect reconstruction of the
      knee with either of the above-mentioned conditions. In these cases, the flaps
      relied on the reverse blood flow through the rectus femoris branch and showed
      complete survival postoperatively. We believe that the reverse flow from the
      rectus femoris branch could be an alternative blood supply for the dALT flap in
      the presence of hypoplasia of the LCFA descending branch or compromise of the
      vascular connection between the descending branch and the articular geniculate
      network.

PMID- 29175134
TI  - Rapidly growing mycobacteria infections among "cosmetic tourists" returning to
      the Netherlands.

PMID- 29175135
TI  - A systematic review of near-infrared spectroscopy in flap monitoring: Current
      basic and clinical evidence and prospects.
AB  - BACKGROUND: Near-infrared spectroscopy (NIRS) has been reported to be a reliable
      non-invasive modality for free flap monitoring; however, the history of its
      application in flap monitoring is short, and there is no definite consensus
      regarding its use at present. OBJECTIVES: The aim of this review is to clarify
      the evidence related to post-operative flap monitoring using NIRS and examine its
      appropriateness and usability. MATERIALS AND METHODS: The PubMed and Web of
      Science databases were searched using the strings "flap monitoring AND near
      infrared spectroscopy" and "flap monitoring AND tissue oxygen saturation," with a
      study period from inception to December 31, 2016. Two authors independently
      extracted articles and assessed the quality of the studies. Articles related to
      NIRS for flap perfusion monitoring were classified and selected regardless of
      study type. RESULTS: A total of 15 clinical studies and 8 animal studies were
      identified and reviewed. The evidence and information on various aspects of NIRS
      flap monitoring were summarized. The overall flap success rate was 99.5%, and the
      flap salvage rate was 91.1%, when measuring StO2 at intervals of every 2 h or
      sooner. Single StO2 monitoring was able to detect vascular compromise with 99.1%
      sensitivity and 99.9% specificity, and earlier than other monitoring methods, but
      additional Hb concentration monitoring was useful for avoiding false negatives
      and differentiating arterial and venous occlusion. CONCLUSIONS: NIRS can be used
      for flap monitoring and displays high accuracy in various situations; however,
      further studies are needed to take full advantage of the potential of NIRS.

PMID- 29175136
TI  - The liquid facelift: First hands-on experience with facial water jet-assisted
      liposuction as an additive technique for rhytidectomy - a case series of 25
      patients.
AB  - OBJECTIVE: Recently, water jet-assisted liposuction (WAL) was successfully
      applied by several other authors to remove fat and induce skin contraction in
      nonfacial body areas. Extending the range of indications for this new method, the
      authors of this article report on their first experience with its use in facial
      contouring, fat harvesting, and hydrodissection of the facial skin flap in
      rhytidectomy in a case series of 25 patients. METHODS: Twenty-five patients
      (median age: 56 years) had facelift surgery under sedation, and the WAL technique
      was used for facial contouring, fat harvesting for facial lipotransfer, and
      hydrodissection of the facial skin flap. Patients were monitored for discomfort
      during the procedure. Complications such as bleeding, postoperative swelling, and
      hematoma formation were observed during a 1-week follow-up period, and intensity
      was rated by two independent surgeons using a special grading system.
      Furthermore, a patient survey (FACE-Q) was performed to analyze the patients'
      satisfaction and perception of the postsurgical esthetic results. RESULTS: The
      WAL technique can be applied under intravenous sedation without causing any
      discomfort in all treated patients [mean 1.16, standard deviation (SD) 0.31].
      Intraoperative bleeding during WAL-assisted facial dissection was judged as not
      present at all times (mean 1.3, SD 0.32). Postoperative swelling (day 1: mean
      1.82, SD 0.28; day 7: mean 1.18, SD 0.28) and hematoma formation following
      surgery (day 1: mean 1.58, SD 0.34; day 7: mean 1.18, SD 0.31) were judged as
      minor in all cases. Overall, no skin necrosis was detected. There was no need for
      revision surgery. More than half of our treated patients (n = 13) answered the
      FACE-Q questionnaire, verifying a high satisfaction rate with beneficial
      treatment results without the occurrence of any major complications. CONCLUSIONS:
      The WAL technique seems to offer a safe and efficient treatment approach for
      facial contouring, facial fat harvesting, and simultaneous facial flap
      hydrodissection with only minor postoperative swelling and hematoma formation.
      Therefore, the authors believe that the WAL technique is a powerful and useful
      tool and should be used in modern facial plastic surgery.

PMID- 29175137
TI  - Evaluation of digestion methods for analysis of trace metals in mammalian tissues
      and NIST 1577c.
AB  - Digestion techniques for ICP analysis have been poorly studied for biological
      samples. This report describes an optimized method for analysis of trace metals
      that can be used across a variety of sample types. Digestion methods were tested
      and optimized with the analysis of trace metals in cancerous as compared to
      normal tissue as the end goal. Anthropological, forensic, oncological and
      environmental research groups can employ this method reasonably cheaply and
      safely whilst still being able to compare between laboratories. We examined
      combined HNO3 and H2O2 digestion at 170  degrees C for human, porcine and bovine
      samples whether they are frozen, fresh or lyophilized powder. Little discrepancy
      is found between microwave digestion and PFA Teflon pressure vessels. The
      elements of interest (Cu, Zn, Fe and Ni) yielded consistently higher and more
      accurate values on standard reference material than samples heated to 75  degrees
      C or samples that utilized HNO3 alone. Use of H2SO4 does not improve homogeneity
      of the sample and lowers precision during ICP analysis. High temperature
      digestions (>165  degrees C) using a combination of HNO3 and H2O2 as outlined are
      proposed as a standard technique for all mammalian tissues, specifically, human
      tissues and yield greater than 300% higher values than samples digested at 75 
      degrees C regardless of the acid or acid combinations used. The proposed
      standardized technique is designed to accurately quantify potential discrepancies
      in metal loads between cancerous and healthy tissues and applies to numerous
      tissue studies requiring quick, effective and safe digestions.

PMID- 29175138
TI  - Polymerization of hexamethylene diisocyanate in solution and a 260.23 m/z [M+H]+
      ion in exposed human cells.
AB  - Hexamethylene diisocyanate (HDI) is an important industrial chemical that can
      cause asthma, however pathogenic mechanisms remain unclear. Upon entry into the
      respiratory tract, HDI's N=C=O groups may undergo nucleophilic addition
      (conjugate) to host molecules (e.g. proteins), or instead react with water
      (hydrolyze), releasing CO2 and leaving a primary amine in place of the original
      N=C=O. We hypothesized that (primary amine groups present on) hydrolyzed or
      partially hydrolyzed HDI may compete with proteins and water as a reaction target
      for HDI in solution, resulting in polymers that could be identified and
      characterized using LC-MS and LC-MS/MS. Analysis of the reaction products formed
      when HDI was mixed with a pH buffered, isotonic, protein containing solution
      identified multiple [M+H]+ ions with m/z's and collision-induced dissociation
      (CID) fragmentation patterns consistent with those expected for dimers
      (259.25/285.23 m/z), and trimers (401.36/427.35 m/z) of partially hydrolyzed HDI
      (e.g. ureas/oligoureas). Human peripheral blood mononuclear cells (PBMCs) and
      monocyte-like U937, but not airway epithelial NCI-H292 cell lines cultured with
      these HDI ureas contained a novel 260.23 m/z [M+H]+ ion. LC-MS/MS analysis of the
      260.23 m/z [M+H]+ ion suggest the formula C13H29N3O2 and a structure containing
      partially hydrolyzed HDI, however definitive characterization will require
      further orthogonal analyses.

PMID- 29175139
TI  - In vitro-in vivo correlations for nicotine transdermal delivery systems evaluated
      by both in vitro skin permeation (IVPT) and in vivo serum pharmacokinetics under
      the influence of transient heat application.
AB  - The in vitro permeation test (IVPT) has been widely used to characterize the
      bioavailability (BA) of compounds applied on the skin. In this study, we
      performed IVPT studies using excised human skin (in vitro) and harmonized in vivo
      human serum pharmacokinetic (PK) studies to evaluate the potential in vitro-in
      vivo correlation (IVIVC) of nicotine BA from two, matrix-type, nicotine
      transdermal delivery systems (TDS). The study designs used for both in vitro and
      in vivo studies included 1h of transient heat (42+/-2 degrees C) application
      during early or late time periods post-dosing. The goal was to evaluate whether
      any IVIVC observed would be evident even under conditions of heat exposure, in
      order to investigate further whether IVPT may have the potential to serve as a
      possible surrogate method to evaluate the in vivo effects of heat on the
      bioavailability of a drug delivered from a TDS. The study results have
      demonstrated that the BA of nicotine characterized by the IVPT studies correlated
      with and was predictive of the in vivo BA of nicotine from the respective TDS,
      evaluated under the matched study designs and conditions. The comparisons of
      single parameters such as steady-state concentration, heat-induced increase in
      partial AUCs and post-treatment residual content of nicotine in TDS from the in
      vitro and in vivo data sets showed no significant differences (p>=0.05). In
      addition, a good point-to-point IVIVC (Level A correlation) for the entire study
      duration was achieved by predicting in vivo concentrations of nicotine using two
      approaches: Approach I requiring only an in vitro data set and Approach II
      involving deconvolution and convolution steps. The results of our work suggest
      that a well designed IVPT study with adequate controls can be a useful tool to
      evaluate the relative effects of heat on the BA of nicotine from TDS with
      different formulations.

PMID- 29175140
TI  - Comparison of in vivo targeting ability between cRGD and collagen-targeting
      peptide conjugated nano-carriers for atherosclerosis.
AB  - Atherosclerosis plaque is a major cause of cardiovascular diseases across the
      globe and a silent killer. There are no physical symptoms of the disease in its
      early stage and current diagnostic techniques cannot detect the small plaques
      effectively or safely. Plaques formed in blood vessels can cause serious clinical
      problems such as impaired blood flow or sudden death, regardless of their size.
      Thus, detecting early stage of plaques is especially more important to
      effectively reduce the risk of atherosclerosis. Nanoparticle based delivery
      systems are recognized as a promising option to fight against this disease, and
      various targeting ligands are typically used to improve their efficiency. So, the
      choice of appropriate targeting ligand is a crucial factor for optimal targeting
      efficiency. cRGD peptide and collagen IV targeting peptide, which binds with the
      alphavbeta3 integrin overexpressed in the neovasculature of the plaque and
      collagen type IV present in the plaque, respectively, are frequently used for the
      targeting of nanoparticles. However, at present no study has directly compared
      these two peptides. Therefore, in this study, we have prepared cRGD or collagen
      IV targeting (Col IV-tg-) peptide conjugated and iron oxide nanoparticle (IONP)
      loaded Pluronic based nano-carriers for systemic comparison of their targeting
      ability towards in vivo atherosclerotic plaque in Apolipoprotein E deficient (Apo
      E-/-) mouse model. Nano-carriers with similar size, surface charge, and IONP
      loading content but with different targeting ligands were analyzed through in
      vitro and in vivo experiments. Near infrared fluorescence imaging and magnetic
      resonance imaging techniques as well as Prussian blue staining were used to
      compare the accumulation of different ligand conjugated nano-caariers in the
      aorta of atherosclerotic mice. Our results indicate that cRGD based targeting is
      more efficient than Col IV-tg-peptide in the early stage of atherosclerosis.

PMID- 29175141
TI  - Large neutral amino acid supplementation as an alternative to the phenylalanine
      restricted diet in adults with phenylketonuria: evidence from adult Pah-enu2
      mice.
AB  - Phenylketonuria treatment mainly consists of a phenylalanine-restricted diet but
      still results in suboptimal neuropsychological outcome, which is at least partly
      based on cerebral monoamine deficiencies, while, after childhood, treatment
      compliance decreases. Supplementation of large neutral amino acids (LNAAs) was
      previously demonstrated in young phenylketonuria mice to target all three
      biochemical disturbances underlying brain dysfunction in phenylketonuria.
      However, both its potential in adult phenylketonuria and the comparison with the
      phenylalanine-restricted diet remain to be established. To this purpose, several
      LNAA supplements were compared with a severe phenylalanine-restricted diet with
      respect to brain monoamine and amino acid concentrations in adult C57Bl/6 Pah
      enu2 mice. Adult phenylketonuria mice received a phenylalanine-restricted diet,
      unrestricted diet supplemented with several combinations of LNAAs or AIN-93M
      control diet for 6 weeks. In addition, adult wild-type mice on AIN-93M diet
      served as controls. The severe phenylalanine-restricted diet in adult
      phenylketonuria mice significantly reduced plasma and brain phenylalanine and
      restored brain monoamine concentrations, while brain concentrations of most
      nonphenylalanine LNAAs remained subnormal. Supplementation of eight LNAAs was
      similarly effective as the severe phenylalanine-restricted diet to restore brain
      monoamines, while brain and plasma phenylalanine concentrations remained markedly
      elevated. These results provide biochemical support for the effectiveness of the
      severe phenylalanine-restricted diet and showed the possibilities of LNAA
      supplementation being equally effective to restore brain monoamines in adult
      phenylketonuria mice. Therefore, LNAA supplementation is a promising alternative
      treatment to phenylalanine restriction in adult phenylketonuria patients to
      further optimize neuropsychological functioning.

PMID- 29175142
TI  - Flaxseed oil rich in omega-3 protects aorta against inflammation and endoplasmic
      reticulum stress partially mediated by GPR120 receptor in obese, diabetic and
      dyslipidemic mice models.
AB  - The "first hit" to atherogenesis is driven by toll-like receptor 4, endoplasmic
      reticulum stress and ultimately metabolic dysfunction. In this study, we
      hypothesized that a flaxseed oil-enriched diet (FS) abolishes these inflammatory
      signaling pathway and restore metabolic homeostasis by activating the fatty acid
      receptor GPR120 in aorta of obese mice. Glucose homeostasis was assessed by GTT
      and ITT; lipidomics was performed using a Hybrid Ion Trap-Orbitrap Mass
      Spectrometer; serum lipids were measured using colorimetric assays; GPR120 and
      infiltrating macrophages were analyzed by immunofluorescence; protein
      immunoprecipitation and gene expression were evaluated by Western blot and RT
      PCR, respectively. There were no differences in body weight and food intake
      between the groups from both strains (Swiss and LDLr-KO mice). GTT and
      cholesterol levels were improved by FS in both mice models. Lipidomics showed an
      increase in omega3 (C18:3) content, meanwhile stearic acid (C18:0) was not
      detected in endothelial tissue in response to FS. Moreover, FS markedly decreased
      pro-inflammatory (IL-1beta, TNF-alpha, pIkappaBalpha, pIKKbeta) and unfolded
      protein response markers (ATF6 and GRP78) in aorta. In Swiss mice, GPR120 was
      partially involved in the omega3-mediated anti-inflammatory actions, disrupting
      TLR4 pathway, but not in LDLr-KO mice. Partial replacement of dietary saturated
      by unsaturated omega3 fatty acids contributes to inhibition of cardiovascular
      risk markers, pro-inflammatory cytokines and ER stress sensors and effectors in
      the aorta. However, downregulation of inflammation is not mediated by arterial
      GPR120 activation.

PMID- 29175143
TI  - Electron linear accelerator production and purification of scandium-47 from
      titanium dioxide targets.
AB  - The photonuclear production of no-carrier-added (NCA) 47Sc from solid NatTiO2 and
      the subsequent chemical processing and purification have been developed. Scandium
      47 was produced by the 48Ti(gamma,p)47Sc reaction with Bremsstrahlung photons
      produced from the braking of electrons in a high-Z (W or Ta) convertor.
      Production yields were simulated with the PHITS code (Particle and Heavy Ion
      Transport-code System) and compared to experimental results. Irradiated TiO2
      targets were dissolved in fuming H2SO4 in the presence of Na2SO4 and 47Sc was
      purified using the commercially available Eichrom DGA resin. Typical 47Sc
      recovery yields were >90% with excellent specific activity for small batches
      (<185 MBq batches).

PMID- 29175144
TI  - Association between Helicobacter pylori infection and cognitive impairment in the
      elderly.
AB  - BACKGROUND/PURPOSE: Helicobacter pylori (H. pylori) infection has been positively
      associated with cognitive impairment. However, previous studies have shown
      inconsistent findings. METHODS: This cross-sectional study included 587 elderly
      participants (age ? 65) from the annual elderly health checkup program at the
      National Taiwan University Hospital from 2011 to 2013. Both global and domain
      specific cognition were assessed using various neuropsychiatric tests.
      Multivariable linear regression and logistic regression models were utilized to
      assess the association between the serum H. pylori IgG level and cognitive
      impairment. RESULTS: Compared with the lowest quartile of H. pylori IgG (Q1), the
      highest quartile (Q4) was associated with lower scores on verbal fluency
      vegetables (beta = -0.24), domain-specific attention [digit span-forward: beta = 
      0.19; odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.03-3.24], and
      attention factors (beta = -0.20; OR= 2.67, 95% CI = 1.51-4.73). No significant
      association was observed for global cognition. Stratified analyses revealed that,
      among men, the highest quartile of serum H. pylori IgG (Q4) was associated with
      impaired scores on verbal fluency-vegetables (beta = -0.38; OR = 3.01, 95% CI =
      1.42-6.38). CONCLUSION: Our findings disclosed a positive association between
      serum H. pylori level and cognitive impairment, which provides important
      information for the primary prevention of cognitive impairment through the
      eradication of H. pylori.

PMID- 29175145
TI  - Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer
      bleeding under proton pump inhibitor use: Methodological issues.

PMID- 29175146
TI  - Early HER2-positive breast cancers: time for a new revolution?

PMID- 29175147
TI  - Durvalumab boosts progression-free survival in NSCLC.

PMID- 29175148
TI  - Lenalidomide plus dexamethasone in multiple myeloma.

PMID- 29175150
TI  - 131I radiation exposure and thyroid cancer.

PMID- 29175149
TI  - Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab
      emtansine plus pertuzumab in patients with HER2-positive breast cancer
      (KRISTINE): a randomised, open-label, multicentre, phase 3 trial.
AB  - BACKGROUND: HER2-targeted treatments have improved outcomes in patients with HER2
      positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings;
      however, some patients remain at risk of relapse or death for many years after
      treatment of early-stage disease. Therefore, new strategies are needed. We did a
      phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer
      that replaces traditional systemic chemotherapy with targeted treatment. METHODS:
      We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational
      Research In Oncology centres (hospitals and specialty cancer centres in Asia,
      Europe, USA, and Canada). Eligible participants were aged 18 years or older with
      centrally confirmed HER2-positive stage II-III operable breast cancer (>2 cm
      tumour size), an Eastern Cooperative Oncology Group performance status of 0-1,
      and a baseline left ventricular ejection fraction of at least 55% (by
      echocardiogram or multiple-gated acquisition scan). We randomly assigned
      participants (1:1) to receive either trastuzumab emtansine plus pertuzumab or
      docetaxel, carboplatin, and trastuzumab plus pertuzumab. We did the randomisation
      via an interactive response system under a permuted block randomisation scheme
      (block size of four), stratified by hormone receptor status, stage at diagnosis,
      and geographical location. Patients received six cycles (every 3 weeks) of
      neoadjuvant trastuzumab emtansine plus pertuzumab (trastuzumab emtansine 3.6
      mg/kg; pertuzumab 840 mg loading dose, 420 mg maintenance doses) or docetaxel,
      carboplatin, and trastuzumab plus pertuzumab (docetaxel 75 mg/m2; carboplatin
      area under the concentration-time curve 6 mg/mL * min; trastuzumab 8 mg/kg
      loading dose, 6 mg/kg maintenance doses) plus pertuzumab [same dosing as in the
      other group]). All treatments were administered intravenously. The primary
      objective was to compare the number of patients who achieved a pathological
      complete response (ypT0/is, ypN0), between groups in the intention-to-treat
      population (two-sided assessment), based on local evaluation of tumour samples
      taken at breast cancer surgery done between 14 days and 6 weeks after completion
      of neoadjuvant therapy. Safety was analysed in patients who received at least one
      dose of study medication. This trial is registered with ClinicalTrials.gov,
      number NCT02131064, and follow-up of the adjuvant phase is ongoing. FINDINGS:
      Between June 25, 2014, and June 15, 2015, we randomly assigned 444 patients to
      neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or
      docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221). A pathological
      complete response was achieved by 99 (44.4%) of 223 patients in the trastuzumab
      emtansine plus pertuzumab group and 123 (55.7%) of 221 patients in the docetaxel,
      carboplatin, and trastuzumab plus pertuzumab group (absolute difference -11.3
      percentage points, 95% CI -20.5 to -2.0; p=0.016). During neoadjuvant treatment,
      compared with patients receiving docetaxel, carboplatin, and trastuzumab plus
      pertuzumab, fewer patients receiving trastuzumab emtansine plus pertuzumab had a
      grade 3-4 adverse event (29 [13%] of 223 vs 141 [64%] of 219) or a serious
      adverse event (11 [5%] of 223 vs 63 [29%] of 219). The most common grade 3-4
      adverse events in the trastuzumab emtansine plus pertuzumab group were decreased
      platelet count (three [1%] of 223 patients vs 11 [5%] of 219 with docetaxel,
      carboplatin, and trastuzumab plus pertuzumab), fatigue (three [1%] vs seven
      [3%]), alanine aminotransferase increase (three [1%] vs four [2%]), and
      hypokalaemia (three [1%] vs five [2%]). The most common grade 3-4 adverse events
      in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group were
      neutropenia (55 [25%] of 219 vs one [<1%] of 223 with trastuzumab emtansine plus
      pertuzumab), diarrhoea (33 [15%] vs 2 [<1%]), and febrile neutropenia (33 [15%]
      vs 0). No deaths were reported during neoadjuvant treatment. INTERPRETATION:
      Traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade
      (docetaxel, carboplatin, and trastuzumab plus pertuzumab) resulted in
      significantly more patients achieving a pathological complete response than HER2
      targeted chemotherapy plus HER2-targeted blockade (trastuzumab emtansine plus
      pertuzumab); however, numerically more grade 3-4 and serious adverse events
      occurred in the chemotherapy plus trastuzumab and pertuzumab group. Further
      efforts to improve the efficacy of chemotherapy without imparting more toxicity
      are warranted. FUNDING: F Hoffmann-La Roche and Genentech.

PMID- 29175151
TI  - Osimertinib improves progression-free survival in NSCLC.

PMID- 29175152
TI  - Transplantation of Human Umbilical Cord Blood Mononuclear Cells Attenuated
      Ischemic Injury in MCAO Rats via Inhibition of NF-kappaB and NLRP3 Inflammasome.
AB  - Accumulated evidence displayed that transplantation of stem cells may be a
      promising approach for the treatment of neurological disorders. However, the
      underlying mechanisms remain to be well elucidated. Moreover, some investigators
      cannot reproduce similar results as the previous. The present results showed that
      transplantation of fresh human umbilical cord blood mononuclear cells (cbMNCs)
      attenuated ischemic damage in middle cerebral artery occlusion (MCAO) rats,
      accompanied with improvement of neurologic deficits, learning and memory
      function. The increase in neovascularization and related molecules such as
      vascular endothelial growth factor (VEGF), Angiopoietin-1 (Ang-1) and endothelium
      specific receptor tyrosine kinase 2 (Tie-2) in the injured brain was observed in
      cbMNCs-treated rats. Moreover, nuclear factor-kappaB (NF-kappaB) activation and
      nucleotide binding and oligomerization domain-like receptor family pyrin domain
      containing 3 (NLRP3) inflammasome were also inhibited by the cells graft,
      resulting in reduction in cleaved caspase-1 and mature interleukin-1beta (IL
      1beta) content. These results suggested that the protective actions of the cells
      on the cerebral ischemia may be related to inhibition of NF-kappaB pathway and
      NLRP3 inflammasome.

PMID- 29175153
TI  - Novel Distinctive Roles of Docking Proteins in Short-term Synaptic Plasticity of
      Frog Neuromuscular Transmission Revealed by Botulinum Neurotoxins.
AB  - Short-term synaptic plasticity (SSP) is a basic mechanism for temporal processing
      of neural information in synaptic transmission. Facilitation, the fastest
      component of SSP, has been extensively investigated with regard to Ca2+ signaling
      and other relevant substances. However, systematic analyses on the slower
      components of SSP, originated by Magleby and Zengel, have remained stagnant for
      decades, as few chemicals directly modifying these slower components have been
      identified. In combination with refined experimental protocols designed to study
      the stimulation frequency-dependence of SSP and botulinum neurotoxins A and C
      (BoNT-A and BoNT-C), we investigated SSP of frog neuromuscular transmission to
      clarify the roles of synaptosomal-associated protein of 25 kDa (SNAP-25) and
      syntaxin, SNARE proteins exclusively participating in vesicular events including
      docking, priming and exocytosis. We found that BoNT-A treatment eliminated slow
      potentiation, and BoNT-C poisoning abolished intermediate augmentation, two
      components of SSP. Fast facilitation was maintained after double poisoning with
      BoNT-A and -C, but the postsynaptic response became biphasic. A novel depression,
      termed repression, emerged by double poisoning. Repression was different from
      depletion because it developed even at a low-frequency stimulation of 1 Hz. We
      conclude that SNAP-25 and syntaxin not only play roles as cooperative exocytotic
      machinery, but also have roles in SSP.

PMID- 29175154
TI  - Immature Status Epilepticus: In Vitro Models Reveal Differences in Cholinergic
      Control and HFO Properties of Adult CA3 Interictal Discharges in Temporal vs
      Septal Hippocampus.
AB  - We have earlier demonstrated that a Status Epilepticus (SE) during CNS
      development has long-lasting effects on cholinergic neurotransmission, detectable
      in vitro and in vivo. In this work, we aimed to localize changes in temporal (T)
      vs septal (S) hippocampus and to correlate adult CA3 interictal epileptiform
      discharge (IED) frequency changes to those of Ripples (R) and Fast Ripples (FR)
      of the High-Frequency Oscillations (HFOs). Spontaneous IEDs were induced by
      bathing slices in Mg2+-free ACSF or in 4-Aminopyridine (4-AP, 50 uM) and data
      were analyzed separately for each model. IED frequencies were similar in same
      origin normal (N) slices across models, but differed in SE slices, being lower in
      Mg2+-free ACSF than in 4-AP, suggesting a post-SE long-term increase in a K+
      conductance. Rs and FRs detected within IEDs had generally higher power in 4-AP
      than in Mg2+-free ACSF; FR/R ratio was the highest in T-SE slices in 4-AP and
      similar in all other slice groups. Carbachol or eserine increased IED rates
      universally, but had region- and conditioning-specific effects on HFOs,
      suggesting that IED frequency and HFOs represent possibly independent indices of
      excitability. The muscarinic antagonist atropine depressed IED rates with
      increasing effectiveness in S slices post-SE in both models. In conclusion, the
      long-term effects of an immature SE are region-specific within the hippocampus,
      affect differently synchronizing components like the IED frequency and HFOs and
      may shape neurotransmitter effects (ACh) on neuronal networks, thus affecting
      seizure threshold and information processing, especially in behavioral conditions
      of rising extracellular ACh levels.

PMID- 29175156
TI  - IL-33/ST2 Pathway as a Rational Therapeutic Target for CNS Diseases.
AB  - Interleukin (IL)-33 is a member of the interleukin-1 cytokine family that is
      produced by many different types of tissues including the central nervous system
      (CNS). IL-33 mediates its effects via its heterodimeric receptor complex,
      comprised of ST2 and the IL-1 receptor accessory protein (IL-1RAcp). As a
      pleiotropic nuclear cytokine, IL-33 is a crucial factor in the development of
      cardiovascular diseases, allergic diseases, infectious diseases, and autoimmune
      diseases. Recently, accumulated evidence shows that the IL-33/ST2 axis plays a
      crucial and diverse role in the pathogenesis of CNS diseases, including
      neurodegenerative diseases, cerebrovascular diseases, infectious diseases,
      traumatic CNS injury, chronic pain, etc. In this review, we discuss the recent
      findings in the cellular signaling of IL-33 and advancement of the role of IL-33
      in several CNS diseases, as well as its therapeutic potential for the treatment
      of those diseases.

PMID- 29175155
TI  - Neuroanatomical Distribution of DEK Protein in Corticolimbic Circuits Associated
      with Learning and Memory in Adult Male and Female Mice.
AB  - DEK, a chromatin-remodeling gene expressed in most human tissues, is known for
      its role in cancer biology and autoimmune diseases. DEK depletion in vitro
      reduces cellular proliferation, induces DNA damage subsequently leading to
      apoptosis, and down-regulates canonical Wnt/beta-catenin signaling, a molecular
      pathway essential for learning and memory. Despite a recognized role in cancer
      (non-neuronal) cells, DEK expression and function is not well characterized in
      the central nervous system. We conducted a gene ontology analysis (ToppGene),
      using a cancer database to identify genes associated with DEK deficiency, which
      pinpointed several genes associated with cognitive-related diseases (i.e.,
      Alzheimer's disease, presenile dementia). Based on this information, we examined
      DEK expression in corticolimbic structures associated with learning and memory in
      adult male and female mice using immunohistochemistry. DEK was expressed
      throughout the brain in both sexes, including the medial prefrontal cortex
      (prelimbic, infralimbic and dorsal peduncular). DEK was also abundant in all
      amygdalar subdivisions (basolateral, central and medial) and in the hippocampus
      including the CA1, CA2, CA3, dentate gyrus (DG), ventral subiculum and entorhinal
      cortex. Of note, compared to males, females had significantly higher DEK
      immunoreactivity in the CA1, indicating a sex difference in this region. DEK was
      co-expressed with neuronal and microglial markers in the CA1 and DG, whereas only
      a small percentage of DEK cells were in apposition to astrocytes in these areas.
      Given the reported inverse cellular and molecular profiles (e.g., cell survival,
      Wnt pathway) between cancer and Alzheimer's disease, these findings suggest a
      potentially important role of DEK in cognition.

PMID- 29175159
TI  - Hierarchical microcrack model for materials exemplified at enamel.
AB  - OBJECTIVE: This article investigates the mechanical properties of a material with
      hierarchically arranged microcracks. METHODS: Hierarchically structured
      biomaterials such as enamel exhibit superior mechanical properties as being stiff
      and damage tolerant at the same time. The common mechanical explanation for this
      behavior is based on the hierarchically structured arrangement of hard minerals
      and soft organics and their cooperative deformation mechanisms. In situ
      mechanical experiments with mm-sized bovine enamel bending bars an scanning
      electron microscope reveal that enamel is able to withstand mechanical loading
      even if it contains microcracks on different lengths scales. To clarify this
      issue an analytical hierarchical microcrack model of non-interacting cracks is
      presented. RESULTS AND SIGNIFICANCE: The model predicts a decrease of the elastic
      modulus and the fracture strength with increasing levels of hierarchy. The
      fracture strain on the other hand may decrease or increase with the number of
      hierarchical levels, depending on the microcrack density. This simple
      hierarchical microcrack model is able to explain already published experiments
      with focused ion beam prepared MUm-sized enamel cantilevers on different
      hierarchical levels. In addition it is shown that microcracking during loading in
      hierarchical materials may lead to substantial pseudoplastic behavior.

PMID- 29175157
TI  - Mapping the Structural Determinants Required for AAVrh.10 Transport across the
      Blood-Brain Barrier.
AB  - Effective gene delivery to the CNS by intravenously administered adeno-associated
      virus (AAV) vectors requires crossing the blood-brain barrier (BBB). To achieve
      therapeutic CNS transgene expression, high systemic vector doses are often
      required, which poses challenges such as scale-up costs and dose-dependent
      hepatotoxicity. To improve the specificity and efficiency of CNS gene transfer, a
      better understanding of the structural features that enable AAV transit across
      the BBB is needed. We generated a combinatorial domain swap library using AAV1, a
      serotype that does not traverse the vasculature, and AAVrh.10, which crosses the
      BBB in mice. We then screened individual variants by phylogenetic and structural
      analyses and subsequently conducted systemic characterization in mice. Using this
      approach, we identified key clusters of residues on the AAVrh.10 capsid that
      enabled transport across the brain vasculature and widespread neuronal
      transduction in mice. Through rational design, we mapped a minimal footprint from
      AAVrh.10, which, when grafted onto AAV1, confers the aforementioned CNS phenotype
      while diminishing vascular and hepatic transduction through an unknown mechanism.
      Functional mapping of this capsid surface footprint provides a roadmap for
      engineering synthetic AAV capsids for efficient CNS gene transfer with an
      improved safety profile.

PMID- 29175160
TI  - The effect of chewing simulation on surface roughness of resin composite when
      opposed by zirconia ceramic and lithium disilicate ceramic.
AB  - OBJECTIVE: To assess the change in surface roughness of nanohybrid resin
      composite (Tetric EvoCeram) after antagonist wear against monolithic zirconia and
      lithium disilicate ceramics through a simulated chewing test using a three
      dimensional (3D) profilometer. METHODS: A total of 40 Tetric EvoCeramTM resin
      composite specimens against either a LavaTM Plus zirconia antagonist (n=20) or
      IPS e.max Press lithium disilicate antagonist (n=20) were prepared for the study.
      The surface roughness profiles of each resin composite before and after an in
      vitro simulated chewing test were analysed using a 3D profilometer and Talymap
      software. After the simulated chewing, the surface profiles of representative
      Tetric EvoCeram specimens from each group were analysed using scanning electron
      microscopy. Independent t-test and paired t-test were used for statistical
      analysis. RESULTS: For both lithium disilicate and zirconia groups, all surface
      roughness parameters (Ra, Rt, Sa, Sq,) of Tetric EvoCeram were significantly
      higher post-chewing compared to pre-chewing (p<0.05); the post-chewing surface
      roughness parameters of Tetric EvoCeram for the lithium disilicate group were
      significantly higher (p<0.05) than in the zirconia group. SIGNIFICANCE: This
      chewing simulation test showed that Tetric EvoCeram composites exhibited a
      rougher surface when opposing lithium disilicate ceramic compared to opposing
      zirconia ceramic.

PMID- 29175161
TI  - Induction of DNA double-strand breaks in human gingival fibroblasts by eluates
      from titanium dioxide modified glass ionomer cements.
AB  - OBJECTIVES: (1) To investigate the genotoxicity of a glass ionomer cement (GIC)
      and GIC incorporated with titanium dioxide nanopoarticle (TiO2NPs) and with
      microparticle (TiO2MPs) on DNA double-strand breaks of human gingival fibroblast
      cells (HGFs). (2) To compare the genotoxic differences between GIC and two
      modified cements. METHODS: TiO2NPsGIC and TiO2MPsGIC were prepared by adding 10%
      w/w of TiO2NPs and TiO2MPs to the GIC powder and hand-mixed followed the
      manufacturer instruction. Dulbecco's Minimum Essential Medium (DMEM) was used as
      a culture medium for HGFs and eluate preparation. Eluates from all groups were
      collected for XTT cell viability assay to obtain EC50 values. gamma-H2AX
      immunofluorescence assay was performed to detect DNA double-strand breaks (DSBs)
      of HGFs. RESULTS: EC50 values were from 38% to 60% and eluate concentrations at
      20% and 5% were selected for gamma-H2AX immunofluorescence assay. At both
      concentrations, HGFs exposed to eluates from all cements groups had fewer mean
      foci per cell and higher percentage of free foci cells than H2O2 (p<0.05). At 20%
      concentration, cells exposed to eluates from both TiO2NPsGIC and TiO2MPsGIC
      groups had fewer mean foci per cell and higher percentage of free foci cell than
      GIC and culture medium (p<0.05). SIGNIFICANCE: Neither GIC nor 10% TiO2-modified
      GICs had a genotoxic effect on HGFs. Both TiO2NPsGIC and TiO2MPsGIC demonstrated
      less genotoxic effect than GIC. When comparing between the two modified cements,
      there was no genotoxic difference between the modified cements from different
      particle sizes (nanoparticle and micro-particle) of TiO2.

PMID- 29175158
TI  - Multi-modal Potentiation of Oncolytic Virotherapy by Vanadium Compounds.
AB  - Oncolytic viruses (OV) are an emerging class of anticancer bio-therapeutics that
      induce antitumor immunity through selective replication in tumor cells. However,
      the efficacy of OVs as single agents remains limited. We introduce a strategy
      that boosts the therapeutic efficacy of OVs by combining their activity with
      immuno-modulating, small molecule protein tyrosine phosphatase inhibitors. We
      report that vanadium-based phosphatase inhibitors enhance OV infection in vitro
      and ex vivo, in resistant tumor cell lines. Furthermore, vanadium compounds
      increase antitumor efficacy in combination with OV in several syngeneic tumor
      models, leading to systemic and durable responses, even in models otherwise
      refractory to OV and drug alone. Mechanistically, this involves subverting the
      antiviral type I IFN response toward a death-inducing and pro-inflammatory type
      II IFN response, leading to improved OV spread, increased bystander killing of
      cancer cells, and enhanced antitumor immune stimulation. Overall, we showcase a
      new ability of vanadium compounds to simultaneously maximize viral oncolysis and
      systemic anticancer immunity, offering new avenues for the development of
      improved immunotherapy strategies.

PMID- 29175162
TI  - A pH-stable, detergent and chelator resistant type I pullulanase from Bacillus
      pseudofirmus 703 with high catalytic efficiency.
AB  - Pullulanase with high catalytic efficiency has attracted great attention from
      both the academic and industrial communities for its wide application in cold
      starch hydrolysis. A novel pullulanase gene pul703 was cloned from a mesophilic
      bacteria Bacillus pseudofirmus 703. Pul703 was characterized to be a type I
      pullulanase with maximal activity at 45 degrees C and good low-temperature
      stability, more than 70% of activity was detected after incubation at 25-35
      degrees C for 72h. Pul703 obtained the maximal activity around pH 7.0-8.0, and
      was highly active and stable over a wide pH range of 5.5-9.5, more than 80% of
      activity was retained after 12h incubation in these pHs. Pul703 was EDTA
      resistant and detergent-tolerant, with a relative activity of 100, 99, and 114.8%
      at the presence of 10mM EDTA, 10% of Triton X-100 and Tween 20, respectively.
      Pul703 can efficiently hydrolyze pullulan with a specific activity of 270U/mg,
      which was higher than all reported type I pullulanases. In addition, Pul703 can
      act synergistically with alpha-amylase BLA to efficiently hydrolyze amylopectin.
      These results suggested that Pul703 was a good candidate for cold starch
      hydrolysis.

PMID- 29175163
TI  - Production and characterization of a novel acidophilic and thermostable xylanase
      from Thermoascus aurantiacu.
AB  - The thermostable fungus, Thermoascus aurantiacus M-2, which produces a novel
      acidophilic and thermostable xylanase was isolated and identified based on its
      morphology and comparison of the internal transcribed spacer rDNA gene sequence.
      The culture conditions and components of medium were optimized for T. aurantiacus
      M-2 to produce xylanase. T. aurantiacus M-2 produced xylanase at a maximum level
      of 39.07 U/mL after 8-d fermentation at 45  degrees C in the optimized medium.
      The purified xylanase produced by T. aurantiacus M-2 has a relative molecular
      mass of approximately 31.0 kD. The characteristics of purified xylanase were
      investigated. The purified T. aurantiacus xylanase exhibited maximum activity at
      75  degrees C and pH 5.0, and it was stable after treatment at a pH range from
      2.0 to 10.0 or a temperature range from 30  degrees C to 80  degrees C for 2-h.
      Mn2+ and Ag+ enhanced xylanase activity to 120.0% and 119.6%, respectively, while
      Mn2+ had the highest inhibition ratio, with a residual activity of 20.7%. This
      study provided a foundation for scaled-up production and application of xylanase.

PMID- 29175164
TI  - Antibacterial activity of a new lectin isolated from the marine sponge Chondrilla
      caribensis.
AB  - A new lectin from the marine sponge Chondrilla caribensis (CCL) was isolated by
      affinity chromatography in Sepharose 6B media. CCL is a homotetrameric protein
      formed by subunits of 15,445 +/-2Da. The lectin showed affinity for disaccharides
      containing galactose and mucin. Mass spectrometric analysis revealed about 50% of
      amino acid sequence of CCL, which showed similarity with a lectin isolated from
      Aplysina lactuca. Secondary structure consisted of 10% alpha-helix, 74% beta
      sheet/beta-turn and 16% coil, and this profile was unaltered in a broad range of
      pH and temperatures. CCL agglutinated Staphylococcus aureus, S epidermidis and
      Escherichia coli, and it was able to reduce biofilm biomass, but showed no
      inhibition of planktonic growth of these bacteria. CCL activity was inhibited by
      alpha-lactose, indicating that Carbohydrate Recognition Domain (CRD) of the
      lectin was involved in antibiofilm activity.

PMID- 29175165
TI  - Functional properties of chickpea protein isolates dried by refractance window
      drying.
AB  - In the present study, the effect of Refractance Window (RW) drying on the
      functional properties of chickpea protein isolates was investigated and compared
      to freeze drying at different pH levels. The functional properties investigated
      were protein solubility, water and oil holding capacity, emulsifying properties,
      foaming properties, flocculation and coalescence indices and textural properties.
      The solubility, oil holding capacity and foam stability of the freeze dried
      protein isolates were determined to be higher than the RW dried samples. On the
      other hand, the RW dried samples had better water holding capacity and emulsion
      stability compared to the freeze dried protein isolates. The emulsion activity
      index, flocculation and coalescence indices of the chickpea protein isolates
      prepared by different drying techniques showed different tendencies depending on
      the pH level. Freeze dried protein isolates exhibited higher gelation ability
      than RW dried samples according to the texture profile analysis. This study
      clearly showed that the drying technique used in the preparation of protein
      isolates can affect their functional properties.

PMID- 29175166
TI  - Extraction and physicochemical characterization of chitin and chitosan from
      Zophobas morio larvae in varying sodium hydroxide concentration.
AB  - Large amount of sodium hydroxide (NaOH) is consumed to remove the protein content
      in chitin biomass during deproteinization. However, excessive NaOH concentration
      used might lead to the reduction of cost effectiveness during chitin extraction.
      Hence, the present study aimed to extract and evaluate the physicochemical
      properties of chitin and chitosan isolated from superworm (Zophobas morio) larvae
      using 0.5M-2.0M of NaOH. The extracted chitin and chitosan were subjected to
      Fourier Transform Infrared Spectroscopy (FT-IR), elemental analysis, Scanning
      Electron Microscope (SEM), Thermogravimetric Analysis (TGA), Differential
      Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The 0.5M NaOH treatment
      resulted in the highest yield of chitin (5.43%), but produced the lowest yield
      (65.84%) of chitosan. The extracted chitin samples had relatively high degree of
      acetylation (DA) (82.39%-101.39%). Both chitin and chitosan showed smooth surface
      with tiny pores. The extracted chitin samples were confirmed as alpha-chitin
      based on the FT-IR and TGA. The chitin samples were amorphous with low degree of
      crystallinity. From TGA, the Chitosan 3 extracted was partially deacetylated.
      Both DPPH radical scavenging and ferric-chelating assay showed positive
      correlation with DD of chitosan isolates. However, the chitosan isolates were not
      fully dissolved, resulting in lower radical scavenging and ferric-chelating
      ability compared to commercial chitosan.

PMID- 29175167
TI  - A dual-function chymotrypsin-like serine protease with plasminogen activation and
      fibrinolytic activities from the GRAS fungus, Neurospora sitophila.
AB  - In this study, we have isolated and characterized a fibrinolytic enzyme from the
      GRAS (Generally Recognized as Safe) fungus, Neurospora sitophila. The enzyme was
      purified by fractional ammonium sulfate precipitation, hydrophobic interaction,
      ion exchange and gel filtration chromatography to 45.2 fold with a specific
      activity of 415.6U/mg protein. The native molecular mass of the enzyme was 49kDa,
      while the denatured molecular mass was 30kDa and 17.5kDa, indicating that the
      enzyme was a hetero-dimer. It was optimally active at 50 degrees C and pH 7.4 and
      stable at human physiological temperature and pH. It was found to be a
      chymotrypsin-like serine protease which cleaved the synthetic chromogenic
      substrate, N-Succinyl-Ala-Ala-Pro-Phe-pNA for which the apparent Km and Vmax
      values were 0.24mM and 4.17*10-5mM/s, respectively. The enzyme hydrolyzed all the
      chains of fibrinogen by cleaving alpha chain first, followed by beta chain and
      then gamma chain. Moreover, the enzyme possessed dual function of direct
      fibrinolysis as well as plasminogen activation. Due to its attractive biochemical
      and fibrinolytic properties and being from a GRAS fungus, the fibrinolytic enzyme
      has application as a safe and efficient thrombolytic drug.

PMID- 29175168
TI  - CD8+ T cells are essential for the effects of enriched environment on hippocampus
      dependent behavior, hippocampal neurogenesis and synaptic plasticity.
AB  - Enriched environment (EE) induces plasticity changes in the brain. Recently, CD4+
      T cells have been shown to be involved in brain plasticity processes. Here, we
      show that CD8+ T cells are required for EE-induced brain plasticity in mice, as
      revealed by measurements of hippocampal volume, neurogenesis in the DG of the
      hippocampus, spinogenesis and glutamatergic synaptic function in the CA of the
      hippocampus. As a consequence, EE-induced behavioral benefits depend, at least in
      part, on CD8+ T cells. In addition, we show that spleen CD8+ T cells from mice
      housed in standard environment (SE) and EE have different properties in terms of
      1) TNFalpha release after in vitro CD3/CD28 or PMA/Iono stimulation 2) in vitro
      proliferation properties 3) CD8+ CD44+ CD62Llow and CD62Lhi T cells repartition
      4) transcriptomic signature as revealed by RNA sequencing. CD8+ T cells purified
      from the choroid plexus of SE and EE mice also exhibit different transcriptomic
      profiles as highlighted by single-cell mRNA sequencing. We show that CD8+ T cells
      are essential mediators of beneficial EE effects on brain plasticity and
      cognition. Additionally, we propose that EE differentially primes CD8+ T cells
      leading to behavioral improvement.

PMID- 29175169
TI  - Outcome of pregnancy with new onset proteinuria and progression to pre-eclampsia:
      A retrospective analysis.
AB  - OBJECTIVE: To examine maternal and neonatal outcomes of gestational proteinuria,
      and to identify maternal characteristics for progression to pre-eclampsia. STUDY
      DESIGN: Retrospective cohort. Included all pregnant women who delivered between
      Jan 2014-Feb 2017 with new onset proteinuria in a single obstetric unit.
      Demographic, maternal and neonatal outcomes were compared. RESULTS: Eighteen
      (25%) out of 73 women with new onset gestational proteinuria developed pre
      eclampsia. The incidence of gestational proteinuria was 0.54%. Compared with
      women that remained normotensive, those that developed hypertension had delivery
      at earlier gestation (p = .02), increased risk of fetal growth restriction (p =
      .01) and lower newborn birthweight (p = .002). Maximal proteinuria and fetal
      growth restriction were independent factors associated with development of pre
      eclampsia. In particular, high proteinuria level >= 2 g/d constitute a major
      predictor for progression (p = .03). CONCLUSION: Increased vigilance for
      antenatal surveillance is important in women with gestational proteinuria as a
      substantial portion progress to pre-eclampsia. Serial growth scan and proteinuria
      assay are suggested to predict possible pre-eclampsia development.

PMID- 29175170
TI  - First-trimester mean arterial blood pressure and the risk of preeclampsia: The
      Great Obstetrical Syndromes (GOS) study.
AB  - OBJECTIVE: To estimate the predictive value of first-trimester mean arterial
      pressure (MAP) for the hypertensive disorders of pregnancy (HDP). STUDY METHODS:
      We performed a prospective cohort study of nulliparous women recruited at 110/7
      136/7 weeks. MAP was calculated from blood pressure measured on both arms
      simultaneously using an automated device taking a series of recordings until
      blood pressure stability was reached. MAP was reported as multiples of the median
      adjusted for gestational age. Participants were followed for development of
      gestational hypertension (GH), preeclampsia (PE), preterm PE (<37 weeks) and
      early-onset (EO) PE (<34 weeks). Receiver operating characteristic curves and the
      area under the curve (AUC) were used to estimate the predictive values of MAP.
      Multivariate logistic regressions were used to develop predictive models
      combining MAP and maternal characteristics. RESULTS: We obtained complete follow
      up in 4700 (99%) out of 4749 eligible participants. GH without PE was observed in
      250 (5.3%) participants, and PE in 241 (5.1%), including 33 (0.7%) preterm PE and
      10 (0.2%) EO-PE. First-trimester MAP was associated with GH (AUC: 0.77; 95%CI:
      0.74-0.80); term PE (0.73; 95%CI: 0.70-0.76), preterm PE (0.80; 95%CI: 0.73-0.87)
      and EO-PE (0.79; 95%CI: 0.62-0.96). At a 10% false-positive rate, first-trimester
      MAP could have predicted 39% of GH, 34% of term PE, 48% of preterm PE and 60% of
      EO-PE. The addition of maternal characteristics improved the predictive values
      (to 40%, 37%, 55% and 70%, respectively). CONCLUSION: First-trimester MAP is a
      strong predictor of GH and PE in nulliparous women.

PMID- 29175171
TI  - Early warning system hypertension thresholds to predict adverse outcomes in pre
      eclampsia: A prospective cohort study.
AB  - OBJECTIVES: To evaluate the association between blood pressure (BP) measurements
      and adverse outcomes in women with pre-eclampsia. STUDY DESIGN: A prospective
      cohort study of women with pre-eclampsia admitted to three South African tertiary
      facilities. BP was measured using the CRADLE Vital Signs Alert (VSA),
      incorporated with a traffic light early warning system; green: systolic BP <140
      mmHg and diastolic BP <90 mmHg, yellow: systolic BP 140-159 and/or diastolic BP
      90-109 mmHg (but neither is above the upper threshold), red: systolic BP >=160
      mmHg and/or diastolic BP >=110 mmHg. MAIN OUTCOME MEASURES: Maternal: death,
      eclampsia, stroke, kidney injury; process measures: magnesium sulfate use,
      Critical Care Unit (CCU) admission; perinatal: stillbirth, neonatal death,
      preterm delivery. RESULTS: Of 1547 women with pre-eclampsia (including 42 twin
      pregnancies), 33.0% of women triggered a red light on admission and 78.6% at
      their highest BP. Severe hypertension and adverse outcomes were common across
      yellow and red categories. Comparing admission red to yellow lights, there was a
      significant increase in kidney injury (OR 1.74, CI 1.31-2.33, trend test p =
      .003), magnesium sulfate use (OR 3.40, CI 2.24-5.18, p < .001) and CCU admission
      (OR 1.50, CI 1.18-1.91, p < .001), but not for maternal death, eclampsia,
      extended perinatal death or preterm delivery. CONCLUSION: The CRADLE VSA, with
      integrated traffic light early warning system, can identify women who are
      hypertensive, at increased risk of severe pre-eclampsia complications and in need
      of escalation of care. Women who triggered a red light were at increased risk of
      kidney injury, magnesium sulfate use and CCU admission.

PMID- 29175172
TI  - A diagnostic curiosity of isolated androstenedione elevation due to
      autoantibodies against horseradish peroxidase label of the immunoassay.
AB  - Two sisters with hirsutism presented with mild hirsutism and isolated, grossly
      elevated (>34.9nmol/L) serum concentrations of androstenedione measured by
      competitive, homogeneous immunoassay. The clinically discordant laboratory
      results prompted us to look for assay interference. In this immunoassay,
      horseradish peroxidase (HRP)-conjugated androstenedione competes with endogenous
      androstenedione for binding with the solid-phase polyclonal rabbit IgG
      antibodies. After a wash step, the amount of signal generated by the bound HRP
      conjugate is inversely proportional to the androstenedione concentration.
      Alternative analysis by tandem mass spectrometry (a good first line option for
      troubleshooting) and repeating the competitive immunoassay after polyethylene
      glycol treatment returned androstenedione concentrations within reference limits.
      These findings suggested that the original result was spuriously elevated due to
      assay interference. Additionally, the patient samples were pre-incubated with
      heterophile blocking reagents, normal rabbit IgG antibodies and HRP-conjugated
      normal goat IgG antibodies, followed by repeat measurement using the immunoassay.
      Only samples pre-incubated with HRP-conjugate returned significantly lower
      androstenedione (9.5 and 12.5nmol/L, respectively), implying neutralisation of
      the interfering antibodies. Androstenedione remained grossly elevated in the
      other experiments. This deductive exercise showed that the interference is due to
      autoantibodies against the HRP label used in the immunoassay. Another immunoassay
      using HRP label (5alpha-dihydrotestosterone) also produced gross elevation that
      was normal by tandem mass spectrometry analysis. Assay interferences, though not
      uncommon, are frequently overlooked. Laboratory results discordant with clinical
      features should prompt consideration of assay interference to avoid unnecessary
      investigations and treatment. This is the first report of autoantibodies against
      the HRP label used in immunoassay.

PMID- 29175173
TI  - Diagnostic and clinical significance of the titin fragment in urine of Duchenne
      muscular dystrophy patients.
AB  - Duchenne muscular dystrophy (DMD) is a fatal progressive muscle wasting disease
      of childhood. Titin in sarcomere is digested by calcium dependent protease. To
      explore muscle damage in DMD, the urinary concentrations of the N-terminal
      fragment of titin were determined using a newly developed enzyme linked immune
      sorbent assay kit. The urinary titin concentrations were normalized to creatinine
      (Cr). A total of 145 urine samples were obtained at a single Japanese hospital
      from 113 DMD patients aged 3-29years. Normalized urinary titin concentration was
      965.8+/-1011.9 (Mean+/-SD) pmol/mg Cr in patients with DMD. This was nearly 700
      fold higher than healthy children (1.4+/-0.8pmol/mg Cr). The concentration was
      significantly higher in DMD than in BMD patients who had significantly higher
      urinary titin than normal. Urinary titin in DMD patients tended to decrease with
      age. The median concentration of urinary titin in the youngest (aged 3-7years)
      and oldest (aged >=16years) groups was 1468.3 and 411.3pmol/mg Cr, respectively,
      with significant difference. Urinary concentration of titin correlated
      significantly with serum creatine kinase concentration, the best-known biomarker
      of DMD. The N-terminal fragment of titin in urine has potential as a diagnostic
      and clinical biomarker for DMD.

PMID- 29175174
TI  - Doxycycline, a Well-Tolerated, Economic, and Effective Alternative for the First
      Line Treatment of Bullous Pemphigoid.

PMID- 29175175
TI  - The relationship between circulating concentration of AMH and LH content in the
      follicle stimulating hormone (FSH) preparations on follicular growth and
      ovulatory response to superovulation in water buffaloes.
AB  - The relationship between circulating concentration of anti-mullerian hormone
      (AMH) and the LH content of follicle stimulating hormone (FSH) preparation on
      follicular growth and ovulatory response in water buffaloes was evaluated. A
      single blood sample was taken from cows (N=31; age: 9.06+/-0.98years) to
      determine systemic AMH. Animals with concentrations higher or lower than 194+/
      30pg/ml were placed into LOW and HIGH AMH groups and were assigned randomly to be
      superovulated FSH containing either a high (FSHp, HLH) or low (FolltropinV, LLH)
      LH content. Follicular growth and ovulation were monitored using transrectal
      ultrasonography. In animals with HIGH systemic AMH, treatment with FSH with a
      high LH content was associated with more small follicles (AMH X FSH; P=0.02). AMH
      had no effect on small follicles in animals treated with LLH. Females with a HIGH
      AMH had greater numbers of small follicles (P=0.01) and total follicles (P=0.005)
      than LOW AMH cows. Animals treated with HLH had more small follicles (P=0.001)
      but fewer large (P<0.001) and total follicles (P=0.0005) than those treated with
      LLH. Among animals with HIGH AMH, those treated with LLH, ovulated more follicles
      than those treated with HLH. (AMH X FSH; P=0.03). In conclusion, selecting
      animals with high AMH concentration and the use of FSH preparations with a lower
      LH content may improve the superovulatory response in water buffaloes.

PMID- 29175176
TI  - Expression of sex hormone receptors in the brain of male and female newly hatched
      chicks.
AB  - Chromosomal sex and steroid hormones play a determining role in brain sexual
      differentiation during chick embryonic development. Hormone effects on the brain
      are associated with the expression pattern of their intracellular receptors,
      which is sexually dimorphic in many species. We determined by Western blot the
      content of progesterone, estrogen, and androgen receptors (PR-A and PR-B,
      ERalpha, and AR, respectively) in the cortex, cerebellum, tectum, and
      hypothalamus of female and male newly hatched chicks. Males presented a higher
      content of PR-B in the tectum whereas females exhibited a higher content of PR-A
      in the hypothalamus. ERalpha was only detected as a band of 66kDa, and it showed
      a higher content in the cerebellum and tectum of females as compared to these
      regions in males. Besides, males exhibited a higher content of AR in the tectum
      than females. Our study suggests that newly hatched chicks show a sexual
      dimorphism in the expression of sex hormone receptors in brain regions involved
      in sexual behavior such as the hypothalamus, and in non-sexual behavior such as
      the optic tectum and the cerebellum.

PMID- 29175177
TI  - Associations between management practices and major reproductive parameters of
      Holstein-Friesian replacement heifers.
AB  - The aim of this study was to assess the relationship between the reproductive
      management practices and the performance of replacement heifers on large
      commercial dairy farms. The individual data of 14,763 heifers, first inseminated
      in 2014, were analysed from 33 Holstein-Friesian dairy herds in Hungary. The
      relationships between management practices and major reproductive parameters (age
      at first service, AFS; age at first calving, AFC; conception risk to first
      insemination, CR1; and pregnancy status at 20 months of age) were examined by
      mixed-effects models, with the herd as the random effect. The results showed that
      farms using oestrus detection aids experienced reduced AFS (p<0.001) and AFC
      (p=0.001). Observation of oestrus for shorter periods instead of continuously
      showed a tendency towards lower AFC (p=0.057) and was associated with higher odds
      of pregnancy at 20 months of age (p=0.020). Heifers on farms using sexed semen
      had younger AFS, but poorer CR1, compared to those using conventional semen
      exclusively (p<0.05). In addition, the odds of heifers being pregnant by 20
      months of age was higher on farms with more experience using sexed semen
      (p=0.020). Frequent pregnancy diagnosis (i.e. more than once per week) was
      associated with younger AFC (p=0.023). Our results suggest the use of certain
      advanced reproductive management practices for heifer reproductive management in
      large dairy herds (e.g. oestrus detection aids), which can improve reproductive
      efficiency considerably, but are currently used only to a limited extent.

PMID- 29175178
TI  - Effect of serum paraoxonase-1 (PON1) activity on follicular development and
      pregnancy rate in cattle.
AB  - Paraoxonase-1 (PON1) activity has been associated with improvement in ovarian
      function in early postpartum dairy cows and improved in vitro embryo development.
      The aim of the current study was to evaluate the potential association among PON1
      activity and follicular growth, diameter of the preovulatory follicle and
      pregnancy per artificial insemination (AI) service in cattle. In Experiment 1,
      cows (n=33) were subjected to an estradiol-progesterone based protocol to control
      time of ovulation. Starting on Day 8 of the protocol, follicular growth and serum
      PON1 activity were monitored. Cows were separated according to the occurrence of
      ovulation into two groups: Ovulatory (Ov; n=22) and Anovulatory (Anov; n=11). The
      serum activity of PON1 was not different between Ov and Anov cows (P=0.94). In
      addition, using a regression model there was no effect of serum PON1 activity on
      the diameter of dominant follicle (r2=0.00; P=0.99). In Experiment 2, cows
      (n=193) were submitted to the same hormonal protocol as in Experiment 1. On the
      day of the timed artificial insemination (TAI), the diameter of dominant follicle
      was evaluated and blood samples were collected for analysis of PON1 activity.
      According to the serum PON1 activity, cows were divided into three groups: Low
      (<70U/mL), Medium (70-90U/mL) or High (>90U/mL) PON1 activity. The overall
      pregnancy rate was 62.7% (121/193), with no difference among PON1 activity
      groups. Additionally, using a regression model there was no effect of serum PON1
      activity on the diameter of the preovulatory follicle (r2=0.03; P=0.65) and
      pregnancy rate (r2=0.005; P=0.94). The results of this study indicate that there
      is no effect of serum PON1 activity on the diameter of preovulatory follicle or
      establishment of pregnancy in cows submitted to time of ovulation synchronization
      protocols.

PMID- 29175179
TI  - Effects of oxytocin and PGF2alpha on uterine contractility in cows with and
      without metritis-An in-vitro study.
AB  - The aim of this study was to investigate the effects of PGF2alpha and oxytocin in
      vitro on myometrial contractility in puerperal uteri. Thirteen puerperal uteri
      were removed and perfused after euthanasia of cows with (n=7) and without
      metritis (n=6). Measurement of uterine contractility was done using four
      piezoelectric crystals, which were implanted into the myometrium along the
      greater curvature of the uterine horn where fetal implantation occurred during
      the previous pregnancy. After 30min of equilibration, oxytocin (5 IU) or
      PGF2alpha (2.5mg Dinoprost) was administered randomly into both uterine arteries,
      and 30min later, the second administration of either oxytocin or PGF2alpha
      occurred. Treatment with oxytocin induced contractions in uteri with metritis and
      uteri without metritis (P<0.05). In uteri with metritis, greater uterine
      contractions occurred after stimulation with oxytocin than in uteri without
      metritis (P<0.05). Treatment with PGF2alpha did not (P>0.05) result in increased
      contractions in the uteri without metrtitis, however, induced an initial decrease
      in contractions followed by an increase (P<0.05) in contractions in uteri with
      metritis. Myometrial and endometrial gene expression of PGF2alpha (FPR) and
      oxytocin receptor (OTR) was greater (P<0.05) in uteri with metritis than in uteri
      without metritis. The results suggest that oxytocin, but not PGF2alpha, is an
      effective uterotonic drug in puerperal cows. Uteri in which metritis was
      diagnosed contracted more strongly after treatment with oxytocin than uteri in
      which metritis was not diagnosed. This effect was paralleled by greater gene
      expression of OTR as well as FPR in uteri with metritis compared with uteri in
      which metritis was not diagnosed.

PMID- 29175180
TI  - Efflux transport of estrogen glucuronides by human MRP2, MRP3, MRP4 and BCRP.
AB  - Estrone, estradiol and estriol are endogenous human estrogens that are rapidly
      conjugated with glucuronic acid in both intestinal and hepatic epithelial cells.
      The resulting glucuronides, estrone-3-glucuronide (E1-G), estradiol-3- and 17
      glucuronides (E2-3G and E2-17G), as well as estriol-3- and 16-glucuronides (E3-3G
      and E3-16G) are found in human plasma and urine. Unlike E2-17G, the efflux
      transport of other estrogen glucuronides by human transporters has not yet been
      investigated comprehensively. We have studied the transport of E1-G, E2-3G, E3
      3G, E3-16G and estrone-3-sulfate (E1-S), another important estrogen conjugate,
      using the vesicular transport assay with recombinant human MRP2, MRP3, MRP4, MDR1
      and BCRP that were expressed in insect cells. The transport screening assays
      revealed that whereas E1-S was a good and specific substrate for BCRP, the less
      transporter-specific conjugates, E1-G and E2-3G, were still transported by BCRP
      at 10-fold higher rates than E1-S. BCRP also transported E3-16G at higher rates
      than the studied MRPs, while it transported E3-3G at lower rates than MRP3. MRP2
      exhibited lower or equal transport rates of E1-G, E2-3G, E3-3G and E3-16G in
      comparison to MRP3 and BCRP in the screening assays, mainly due to its high Km
      values, between 180 and 790 MUM. MRP3 transported all the tested glucuronides at
      rather similar rates, at Km values below 20 MUM, but lower Vmax values than other
      transporters. In the case of E3-3G, MRP3 was the most active transporter in the
      screening assay. MRP4 transported only E3-16G at considerable rates, while none
      of the tested estrogen conjugates was transported by MDR1 at higher rates than
      control vesicles. These new results, in combination with previously reported in
      vivo human data, stimulate our understanding on the substrate specificity and
      role of efflux transporters in disposition of estrogen glucuronides in humans.

PMID- 29175181
TI  - Cross-cultural adaptation and measurement properties of the Brazilian Version of
      the Michigan Neuropathy Screening Instrument.
AB  - BACKGROUND: The Michigan Neuropathy Screening Instrument is an easy-to-use
      questionnaire aimed at screening and detecting diabetic polyneuropathy.
      OBJECTIVE: To translate and cross-culturally adapt the MNSI to Brazilian
      Portuguese and evaluate its measurement properties. METHODS: Two bilingual
      translators translated from English into Brazilian Portuguese and made a
      synthetic version. The synthetic version was back translated into English. A
      committee of specialists and the translator checked the cultural adaptations and
      developed a pre-final questionnaire in Brazilian Portuguese (prefinal version).
      In pretesting, the prefinal version was applied to a sample of 34 subjects in
      which each subject was interviewed to determine whether they understood each
      item. For the later assessment of measurement properties, 84 subjects were
      assessed. RESULTS: A final Brazilian Portuguese version of the instrument was
      produced after obtaining 80% agreement (SEM<0.01%) among diabetic patients and
      specialists. We obtained excellent intra-rater reliability (ICC3,1=0.90), inter
      rater reliability (ICC2,1=0.90) and within-subject reliability ICC3,1=0.80,
      excellent internal consistency (Cronbach's alpha>0.92), reasonable construct
      validity for the association between the MNSI and Neuropathy Symptom Score
      (r=0.46, p<0.05) and excellent association between the MNSI and Neuropathy
      Disability Score (r=0.79, p<0.05). We did not detect floor and ceiling effects
      (<9.5% of patients with maximum scores). CONCLUSIONS: The Brazilian Portuguese
      version of the MNSI is suitable for application in the Brazilian diabetic
      population and is a reliable tool for the screening and detection of DPN. The
      MNSI can be used both in clinical practice and also for research purposes.

PMID- 29175182
TI  - Impact of diesel exhaust exposure on the liver of mice fed on omega-3
      polyunsaturated fatty acids-deficient diet.
AB  - Exposure to diesel exhaust (DE) exacerbates non-alcoholic fatty liver disease,
      and may systemically affect lipid metabolism. Omega-3 polyunsaturated fatty acids
      (n-3 PUFA) have anti-inflammatory activity and suppresses hepatic triacylglycerol
      accumulation, but many daily diets are deficient in this nutrient. Therefore, the
      effect of DE exposure in mice fed n-3 PUFA-deficient diet was investigated. Mice
      were fed control chow or n-3 PUFA-deficient diet for 4 weeks, then exposed to
      clean air or DE by inhalation for further 4 weeks. Liver histology, plasma
      parameters, and expression of fatty acid synthesis-related genes were evaluated.
      N-3 PUFA-deficient diet increased hepatic lipid droplets accumulation and
      expression of genes promoting fatty acid synthesis: Acaca, Acacb, and Scd1. DE
      further increased the plasma leptin and the expression of fatty acid synthesis
      related genes: Acacb, Fasn, and Scd1. N-3 PUFA-deficient diet and DE exposure
      potentially enhanced hepatic fatty acid synthesis and subsequently accumulation
      of lipid droplets. The combination of low-dose DE exposure and intake of n-3 PUFA
      deficient diet may be an additional risk factor for the incidence of non
      alcoholic fatty liver disease. The present study suggests an important mechanism
      for preventing toxicity of DE on the liver through the incorporation of n-3 PUFAs
      in the diet.

PMID- 29175183
TI  - Benefit and risk assessment of increasing potassium intake by replacement of
      sodium chloride with potassium chloride in industrial food products in Norway.
AB  - High sodium chloride (NaCl) intake is associated with health risks. NaCl may be
      replaced by potassium chloride (KCl) to decrease sodium intake. However,
      increased potassium may also have negative health effects. We conducted a benefit
      and risk assessment of increasing potassium by ratios of 30:70, 50:50, 70:30
      (weight % K+: weight % Na+) in children, adolescents and adults in Norway, using
      intake data from national food consumption surveys and available literature on
      potassium health effects. An intake of at least 3.5 g/day of potassium decreases
      risk of stroke and hypertension, and this level was used in the benefit
      assessment of the healthy population. Three g/day of potassium added to mean food
      intake is assumed safe, and these levels were used in the risk assessment. Not
      all persons reached the protective level of potassium, and increasing numbers
      exceeded the safe levels, in these scenarios. In addition, elderly above 85 years
      and infants below one year of age, as well as several patient groups and
      medication users, are particularly vulnerable to hyperkalemia. In conclusion, the
      number of Norwegians facing increased risk is far greater than the number likely
      to benefit from this replacement of sodium with potassium in industrially
      produced food.

PMID- 29175184
TI  - Assessment of workers' exposure to microorganisms when using biological
      degreasing stations.
AB  - Biological degreasing stations (BDSs) are used by mechanics. These BDSs use a
      water-based solution with a microbial degradation process. Occupational exposure
      during the use of BDSs has not been reported and few studies have identified the
      bacteria present. The objectives were to measure the concentration of
      microorganisms during BDSs' use and monitor the bacterial community in the liquid
      over time. Five mechanical workshops were studied. Six 30-min samples were taken
      at each workshop over one year. Bioaerosols in the ambient air samples were
      collected with Andersen impactors near the BDS Bioaerosols in the workers'
      breathing zone (WBZ) were collected on filters. Fresh bio-degreasing fluids were
      collected from unopened containers, and used bio-degreasing fluids were collected
      in the BDS. The results show that the use of BDSs does not seem to increase
      bioaerosols concentrations in the WBZ (concentrations lower than 480 CFU/m3) and
      that the bacterial communities (mainly yeasts, Bacillus subtilis and Pseudomonas
      aeruginosa) in the bio-degreasing fluids change through time and differ from the
      original community (B. subtilis). This study established that workers using BDSs
      were exposed to low levels of bioaerosols. No respiratory protection is
      recommended based on bioaerosols concentrations, but gloves and strict personal
      hygiene practices are essential.

PMID- 29175185
TI  - RIFM fragrance ingredient safety assessment, heptanal dimethyl acetal, CAS
      Registry Number 10032-05-0.

PMID- 29175187
TI  - Safety assessment of the use of Bacillus-based cleaning products.
AB  - Non-pathogenic Bacillus species used in cleaning products produce the appropriate
      enzymes to degrade stains and soils. However, there is little scientific data
      regarding the human exposure by inhalation of Bacillus spores during or after use
      of microbial-based cleaning products. Herein, air samples were collected at
      various locations in a ventilated, carpeted, residential room to determine the
      air concentration of viable bacteria and spores during and after the application
      of microbial-based carpet cleaning products containing Bacillus spores. The
      influence of human activities and vacuuming was investigated. Bioaerosol levels
      associated with use and post-application activities of whole room carpet
      treatments were elevated during post-application activity, but quickly returned
      to the indoor background range. Use of trigger spray spot applications generated
      aerosolized spores in the immediate vicinity, however, their use pattern and the
      generation of mostly non-respirable particles suggest minimal risks for pulmonary
      exposure from their use. The aerosol counts associated with use of these
      microbial-based cleaners were below the recommendation for safe exposure levels
      to non-pathogenic and non-toxigenic microorganisms except during application of
      the spot cleaner. The data presented suggest that carpet cleaning products,
      containing non-pathogenic Bacillus spores present a low potential for inhalation
      exposure and consequently minimal risk of adverse effects.

PMID- 29175186
TI  - RIFM fragrance ingredient safety assessment, 4-Hexen-1-ol, (4Z)-, CAS Registry
      Number 928-91-6.

PMID- 29175189
TI  - RIFM fragrance ingredient safety assessment, 3-methyl-1-pentanol, CAS Registry
      Number 589-35-5.

PMID- 29175188
TI  - RIFM fragrance ingredient safety assessment, (Z)-4-hepten-1-ol, CAS Registry
      Number 6191-71-5.

PMID- 29175190
TI  - Inhibition of protein tyrosine phosphatase 1B by flavonoids: A structure -
      activity relationship study.
AB  - The classical non-transmembrane protein tyrosine phosphatase 1B (PTP1B) has
      emerged as a key negative regulator of insulin signaling pathways that leads to
      insulin resistance, turning this enzyme a promising therapeutic target in the
      management of type 2 diabetes mellitus (T2DM). In the present work, the in vitro
      inhibitory activity of a panel of structurally related flavonoids, for
      recombinant human PTP1B was studied and the type of inhibition of the most active
      compounds further evaluated. The majority of the studied flavonoids was tested in
      this work for the first time, including flavonoid C13, which was the most potent
      inhibitor. It was observed that the ability to inhibit PTP1B depends on the
      nature, position and number of substituents in the flavonoid structure, as the
      presence of both 7- and 8-OBn groups in the A ring, together with the presence of
      both 3' and 4'-OMe groups in the B ring and the 3-OH group in the C ring; these
      substituents increase the flavonoids' ability to inhibit PTP1B. In conclusion,
      some of the tested flavonoids seem to be promising PTP1B inhibitors and potential
      effective agents in the management of T2DM, by increasing insulin sensitivity.

PMID- 29175191
TI  - RIFM fragrance ingredient safety assessment, cis-5-octen-1-ol CAS Registry Number
      64275-73-6.

PMID- 29175192
TI  - RIFM fragrance ingredient safety assessment, 3-tert-butylcyclohexyl acetate, CAS
      Registry Number 31846-06-7.

PMID- 29175194
TI  - Brain signature of mild stages of cognitive and behavioral impairment in
      amyotrophic lateral sclerosis.
AB  - We aimed to assess the brain signature of cognitive and behavioral impairment in
      C9orf72-negative non-demented ALS patients. The study included 50 amyotrophic
      lateral sclerosis (ALS) patients (out of 75 initially recruited) and 38 healthy
      controls. High-resolution T1-weighted and spin-echo diffusion tensor images were
      acquired in a 3T MRI scanner. The multi atlas-based analysis protocol and the
      FreeSurfer tool were employed for gray matter assessment, and fiber tractography
      for white matter evaluation. Cognitively impaired ALS patients (n = 12) had
      bilateral amygdalae and left thalamic volumetric reduction compared to non
      impaired ALS patients. Behaviorally impaired ALS patients (n = 14) had lower
      fractional anisotropy (FA) at the fornix in comparison with healthy subjects.
      These parameters did correlate with cognitive/behavioral scores, but not with
      motor-functional parameters in the ALS cohort. We believe that basal ganglia and
      fornix damage might be related to cognitive and behavioral impairment across ALS
      frontotemporal dementia continuum. Also, distinct anatomical areas seem to
      influence the behavioral and cognitive status of these individuals.

PMID- 29175193
TI  - RIFM fragrance ingredient safety assessment, Amylcyclohexyl acetate (mixed
      isomers), CAS Registry Number 67874-72-0.

PMID- 29175195
TI  - Regarding "Does Ulipristal Acetate Affect Surgical Experience at Laparoscopic
      Myomectomy?"

PMID- 29175196
TI  - Authors' Reply.

PMID- 29175197
TI  - Crash laparotomy with supra-celiac aortic clamping.

PMID- 29175198
TI  - Cost of diabetic care in India: An inequitable picture.
AB  - AIM: Diabetes is a growing public health problem in India which is soon going to
      become the 'diabetes capital' of the world. It requires regular care and follow
      up. We aimed to estimate the household out-of-pocket (OOP) expenditure and
      catastrophic expenditure due to hospitalization and outpatient care as a result
      of diabetes. MATERIALS AND METHODS: Secondary analysis of nationally
      representative data for India collected by National Sample Survey Organization in
      2014, reporting on health service utilization and health care related OOP
      expenditure by income quintiles and by type of health facility (public or
      private). RESULTS: The median household OOP expenditure from hospitalization due
      to diabetes was USD 151, and was 3 times higher among the richest quintile
      compared to the poorest quintile (p<0.001). There was a significantly higher
      prevalence (p<0.001) of catastrophic expenditure among the poorest quintile (36%)
      compared to the richest (14%). Median private sector OOP hospitalization
      expenditure was four times higher than the public sector (p<0.001). Medicines
      accounted for 41% and 69% of public sector hospitalization and outpatient care
      respectively. Concentration indices show gross inequity in hospitalization
      expenditure, prevalence of catastrophic expenditure and utilization of public
      health facility. CONCLUSION: Households with diabetic patients incur a high risk
      of catastrophic expenditure, particularly for those in the lowest income
      quintiles and those seeking care in the private sector. Increased availability
      and access to essential drugs and strengthening of public facilities will
      significantly reduce OOP expenditure.

PMID- 29175199
TI  - Towards a neurodynamical understanding of the prodrome in schizophrenia.
AB  - The identification of biomarkers for the early diagnosis of schizophrenia that
      could inform novel treatment developments is an important objective of current
      research. This paper will summarize recent work that has investigated changes in
      oscillatory activity and event-related potentials with
      Electro/Magnetoencephalography (EEG/MEG) in participants at high-risk for the
      development of schizophrenia, highlighting disruptions in sensory and cognitive
      operations prior to the onset of the syndrome. Changes in EEG/MEG-data are
      consistent with evidence for alterations in Glutamatergic and GABAergic
      neurotransmission as disclosed by Magnetic Resonance Spectroscopy and brain
      stimulation, indicating changes in Excitation/Inhibition balance parameters prior
      to the onset of psychosis. Together these data emphasize the importance of
      research into neuronal dynamics as a crucial approach to establish functional
      relationships between impairments in neural circuits and emerging psychopathology
      that together could be fundamental for early intervention and the identification
      of novel treatments for emerging psychosis.

PMID- 29175200
TI  - Quasi-periodic patterns of intrinsic brain activity in individuals and their
      relationship to global signal.
AB  - Quasiperiodic patterns (QPPs) as reported by Majeed et al., 2011 are prominent
      features of the brain's intrinsic activity that involve important large-scale
      networks (default mode, DMN; task positive, TPN) and are likely to be major
      contributors to widely used measures of functional connectivity. We examined the
      variability of these patterns in 470 individuals from the Human Connectome
      Project resting state functional MRI dataset. The QPPs from individuals can be
      coarsely categorized into two types: one where strong anti-correlation between
      the DMN and TPN is present, and another where most areas are strongly correlated.
      QPP type could be predicted by an individual's global signal, with lower global
      signal corresponding to QPPs with strong anti-correlation. After regression of
      global signal, all QPPs showed strong anti-correlation between DMN and TPN. QPP
      occurrence and type was similar between a subgroup of individuals with extremely
      low motion and the rest of the sample, which shows that motion is not a major
      contributor to the QPPs. After regression of estimates of slow respiratory and
      cardiac induced signal fluctuations, more QPPs showed strong anti-correlation
      between DMN and TPN, an indication that while physiological noise influences the
      QPP type, it is not the primary source of the QPP itself. QPPs were more similar
      for the same subjects scanned on different days than for different subjects.
      These results provide the first assessment of the variability in individual QPPs
      and their relationship to physiological parameters.

PMID- 29175201
TI  - Neuroanatomical substrate of noise sensitivity.
AB  - Recent functional studies suggest that noise sensitivity, a trait describing
      attitudes towards noise and predicting noise annoyance, is associated with
      altered processing in the central auditory system. In the present work, we
      examined whether noise sensitivity could be related to the structural anatomy of
      auditory and limbic brain areas. Anatomical MR brain images of 80 subjects were
      parcellated with FreeSurfer to measure grey matter volume, cortical thickness,
      cortical area and folding index of anatomical structures in the temporal lobe and
      insular cortex. The grey matter volume of amygdala and hippocampus was measured
      as well. According to our findings, noise sensitivity is associated with the grey
      matter volume in the selected structures. Among those, we propose and discuss
      particular areas, previously linked to auditory perceptual, emotional and
      interoceptive processing, in which larger grey matter volume seems to be related
      to higher noise sensitivity.

PMID- 29175202
TI  - Brain correlates of constituent structure in sign language comprehension.
AB  - During sentence processing, areas of the left superior temporal sulcus, inferior
      frontal gyrus and left basal ganglia exhibit a systematic increase in brain
      activity as a function of constituent size, suggesting their involvement in the
      computation of syntactic and semantic structures. Here, we asked whether these
      areas play a universal role in language and therefore contribute to the
      processing of non-spoken sign language. Congenitally deaf adults who acquired
      French sign language as a first language and written French as a second language
      were scanned while watching sequences of signs in which the size of syntactic
      constituents was manipulated. An effect of constituent size was found in the
      basal ganglia, including the head of the caudate and the putamen. A smaller
      effect was also detected in temporal and frontal regions previously shown to be
      sensitive to constituent size in written language in hearing French subjects
      (Pallier et al., 2011). When the deaf participants read sentences versus word
      lists, the same network of language areas was observed. While reading and sign
      language processing yielded identical effects of linguistic structure in the
      basal ganglia, the effect of structure was stronger in all cortical language
      areas for written language relative to sign language. Furthermore, cortical
      activity was partially modulated by age of acquisition and reading proficiency.
      Our results stress the important role of the basal ganglia, within the language
      network, in the representation of the constituent structure of language,
      regardless of the input modality.

PMID- 29175203
TI  - Effects of bilingualism on white matter integrity in older adults.
AB  - Bilingualism can delay the onset of dementia symptoms and has thus been
      characterized as a mechanism for cognitive or brain reserve, although the origin
      of this reserve is unknown. Studies with young adults generally show that
      bilingualism is associated with a strengthening of white matter, but there is
      conflicting evidence for how bilingualism affects white matter in older age.
      Given that bilingualism has been shown to help stave off the symptoms of dementia
      by up to four years, it is crucial that we clarify the mechanism underlying this
      reserve. The current study uses diffusion tensor imaging (DTI) to compare
      monolinguals and bilinguals while carefully controlling for potential confounds
      (e.g., I.Q., MMSE, and demographic variables). We show that group differences in
      Fractional Anisotropy (FA) and Radial Diffusivity (RD) arise from multivariable
      interactions not adequately controlled for by sequential bivariate testing. After
      matching and statistically controlling for confounds, bilinguals still had
      greater axial diffusivity (AD) in the left superior longitudinal fasciculus than
      monolingual peers, supporting a neural reserve account for healthy older
      bilinguals.

PMID- 29175204
TI  - Cerebral peak alpha frequency predicts individual differences in pain
      sensitivity.
AB  - The identification of neurobiological markers that predict individual
      predisposition to pain are not only important for development of effective pain
      treatments, but would also yield a more complete understanding of how pain is
      implemented in the brain. In the current study using electroencephalography
      (EEG), we investigated the relationship between the peak frequency of alpha
      activity over sensorimotor cortex and pain intensity during capsaicin-heat pain
      (C-HP), a prolonged pain model known to induce spinal central sensitization in
      primates. We found that peak alpha frequency (PAF) recorded during a pain-free
      period preceding the induction of prolonged pain correlated with subsequent pain
      intensity reports: slower peak frequency at pain-free state was associated with
      higher pain during the prolonged pain condition. Moreover, the degree to which
      PAF decreased between pain-free and prolonged pain states was correlated with
      pain intensity. These two metrics were statistically uncorrelated and in
      combination were able to account for 50% of the variability in pain intensity.
      Altogether, our findings suggest that pain-free state PAF over relevant sensory
      systems could serve as a marker of individual predisposition to prolonged pain.
      Moreover, slowing of PAF in response to prolonged pain could represent an
      objective marker for subjective pain intensity. Our findings potentially lead the
      way for investigations in clinical populations in which alpha oscillations and
      the brain areas contributing to their generation are used in identifying and
      formulating treatment strategies for patients more likely to develop chronic
      pain.

PMID- 29175205
TI  - Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery Presenting
      in Adulthood: A French Nationwide Retrospective Study, an Editorial Commentary.
AB  - Adults with anomalous left coronary artery from the pulmonary artery typically
      have multiple venous and arterial collateral arteries surrounding the artery,
      making precise ligation imperative. Most physicians delay mitral valve repair
      until left ventricular function improves allowing for reperfusion through a 2
      coronary system reimplanting the anomalous left coronary artery from the
      pulmonary artery into the aorta.

PMID- 29175206
TI  - Stochastic simulation of multiscale complex systems with PISKaS: A rule-based
      approach.
AB  - Computational simulation is a widely employed methodology to study the dynamic
      behavior of complex systems. Although common approaches are based either on
      ordinary differential equations or stochastic differential equations, these
      techniques make several assumptions which, when it comes to biological processes,
      could often lead to unrealistic models. Among others, model approaches based on
      differential equations entangle kinetics and causality, failing when complexity
      increases, separating knowledge from models, and assuming that the average
      behavior of the population encompasses any individual deviation. To overcome
      these limitations, simulations based on the Stochastic Simulation Algorithm (SSA)
      appear as a suitable approach to model complex biological systems. In this work,
      we review three different models executed in PISKaS: a rule-based framework to
      produce multiscale stochastic simulations of complex systems. These models span
      multiple time and spatial scales ranging from gene regulation up to Game Theory.
      In the first example, we describe a model of the core regulatory network of gene
      expression in Escherichia coli highlighting the continuous model improvement
      capacities of PISKaS. The second example describes a hypothetical outbreak of the
      Ebola virus occurring in a compartmentalized environment resembling cities and
      highways. Finally, in the last example, we illustrate a stochastic model for the
      prisoner's dilemma; a common approach from social sciences describing complex
      interactions involving trust within human populations. As whole, these models
      demonstrate the capabilities of PISKaS providing fertile scenarios where to
      explore the dynamics of complex systems.

PMID- 29175207
TI  - Dynasore suppresses proliferation and induces apoptosis of the non-small-cell
      lung cancer cell line A549.
AB  - Lung cancer is the leading cause of cancer death worldwide, and most of all cases
      are non-small-cell lung cancer. Lung cancer is associated with dysregulation of
      mitochondrial fusion and fission, and inhibition of the fission regulator Dynamin
      related protein 1 (Drp1) reduces proliferation and increases apoptosis of lung
      cancer cells. Dynasore is a small molecule non-selective inhibitor of the GTPase
      activity of dynamin 1, dynamin 2, and Drp1 in vivo and in vitro. Here, we
      investigated the effects of dynasore on the proliferation and apoptosis of A549
      lung cancer cells, alone and in combination with the chemotherapeutic drug
      cisplatin. We found that cisplatin increased mitochondrial fission and dynamin 2
      expression, whereas dynasore had the opposite effects. However, both cisplatin
      and dynasore independently induced mitochondrial oxidative stress, leading to
      mitochondrial dysfunction, reduced cell proliferation, and enhanced apoptosis.
      Importantly, dynasore significantly augmented the anti-cancer effects of
      cisplatin. To the best of our knowledge, this is the first report that dynasore
      inhibits proliferation and induces apoptosis of lung cancer cells, and enhances
      the inhibitory effects of cisplatin.

PMID- 29175208
TI  - Overexpression of acetyl CoA carboxylase beta exacerbates podocyte injury in the
      kidney of streptozotocin-induced diabetic mice.
AB  - A single nucleotide polymorphism (SNP) within the acetyl CoA carboxylase (ACC)
      beta gene (ACACB), rs2268388, has been shown to be associated with susceptibility
      to development of proteinuria in patients with type 2 diabetes. To investigate
      the biological roles of ACCbeta in the pathogenesis of diabetic nephropathy, we
      examined the effects of overexpression of ACACB using podocyte-specific ACACB
      transgenic mice or ACACB-overexpressing murine podocytes. Podocyte-specific ACACB
      transgenic mice or littermate mice were treated with streptozotocin (STZ) to
      induce diabetes, and 12 weeks after induction of diabetes, we examined the
      expression of podocyte markers to evaluate the degree of podocyte injury in these
      mice. We also examined the effects of ACCbeta on podocyte injury in ACACB- or
      LacZ-overexpressing murine podocytes. Podocyte-specific ACACB overexpression did
      not cause visible podocyte injury in non-diabetic mice. In STZ-induced diabetic
      mice, ACACB-transgenic mice showed a significant increase in urinary albumin
      excretion, accompanied by decreased synaptopodin expression and podocin
      mislocalization in podocytes, compared with wild-type mice. In cultured murine
      podocytes, overexpression of ACACB significantly decreased synaptopodin
      expression and reorganized stress fibers under high glucose conditions, but not
      in normal glucose conditions. The decrease of synaptopodin expression and
      reorganized stress fibers observed in ACACB overexpressing cells cultured under
      high glucose conditions was reversed by a treatment of 5-aminoimidazole-4
      carboxamide-1-beta-4-ribofuranoside (AICAR), activator of AMP-activated protein
      kinase (AMPK). The excess of ACCbeta might contribute to exacerbation of podocyte
      injury in the kidney of an animal model for diabetes mellitus, and the
      AMPK/ACCbeta pathway may be a novel therapeutic target for the prevention of
      diabetes-related podocyte injury.

PMID- 29175209
TI  - The protective role of low-concentration alcohol in high-fructose induced adverse
      cardiovascular events in mice.
AB  - Cardiovascular disease remains a worldwide public health issue. As fructose
      consumption is dramatically increasing, it has been demonstrated that a fructose
      rich intake would increase the risk of cardiovascular disease. In addition,
      emerging evidences suggest that low concentration alcohol intake may exert a
      protective effect on cardiovascular system. This study aimed to investigate
      whether low-concentration alcohol consumption would prevent the adverse effects
      on cardiovascular events induced by high fructose in mice. From the results of
      hematoxylin-eosin staining, echocardiography, heart weight/body weight ratio and
      the expression of hypertrophic marker ANP, we found high-fructose result in
      myocardial hypertrophy and the low-concentration alcohol consumption would
      prevent the cardiomyocyte hypertrophy from happening. In addition, we observed
      low-concentration alcohol consumption could inhibit mitochondria swollen induced
      by high-fructose. The elevated levels of glucose, triglyceride, total cholesterol
      in high-fructose group were reduced by low concentration alcohol. Low expression
      levels of SIRT1 and PPAR-gamma induced by high-fructose were significantly
      elevated when fed with low-concentration alcohol. The histone lysine 9
      acetylation (acH3K9) level was decreased in PPAR-gamma promoter in high-fructose
      group but elevated when intake with low concentration alcohol. The binding levels
      of histone deacetylase SIRT1 were increased in the same region in high-fructose
      group, while the low concentration alcohol can prevent the increased binding
      levels. Overall, our study indicates that low-concentration alcohol consumption
      could inhibit high-fructose related myocardial hypertrophy, cardiac mitochondria
      damaged and disorders of glucose-lipid metabolism. Furthermore, these findings
      also provide new insights into histone acetylation-deacetylation mechanisms of
      low-concentration alcohol treatment that may contribute to the prevention of
      cardiovascular disease induced by high-fructose intake.

PMID- 29175210
TI  - Participation of cysteine 30 residue in the folding process of ovalbumin
      evaluated in a refolding experiment using cysteine mutants.
AB  - To understand the role of cysteine (SH) residues in the folding of hen ovalbumin
      (OVA), SH-mutated OVAs, in which each SH residue was replaced by alanine (C11A,
      C30A, C367A, and C382A), were prepared. SDS-PAGE analysis under non-reducing
      conditions showed that the C11A and C30A mutants produced a disulfide (SS) isomer
      in addition to a protein with a native SS bond (Cys73-Cys120). The susceptibility
      to elastase digestion suggested that the Cys73 residue in the SS isomer
      participates as a counterpart of the SS bond. Upon refolding of the SH-mutated
      OVAs under the denatured and SS-reduced states, only C30A failed to refold into
      an intact form. This indicated that the Cys30 residue plays an important role in
      correct refolding. To confirm this, each of the four SH-mutated OVAs, in which
      the original SS-forming sites (C11/73/120A, C30/73/120A, C73/120/367A, and
      C73/120/382A) were deleted, was constructed and expressed. The C11/73/120A and
      C30/73/120A mutants formed no SS form, in contrast to C73/120A as a control.
      Thus, we concluded that Cys30 participates in the correct folding of OVA, and
      that its SS bond (Cys11-Cys30) is transiently generated during the early folding
      stage to avoid misfolding, and then the native SS form of OVA is regenerated
      through SH-SS exchanges.

PMID- 29175211
TI  - Nutlin sensitizes lung carcinoma cells to interferon-alpha treatment in MDM2
      dependent but p53-independent manner.
AB  - As an anticancer therapeutic, Interferon-alpha (IFNalpha) is used to treat a
      number of malignancies. However, the application of IFNalpha is restricted mostly
      due to its high toxicity. Therefore, novel combination therapeutic regimens are
      required to decrease the toxicity of IFNalpha and enhance its efficacy. Here we
      show that the treatment of p53-deficient human non-small lung carcinoma H1299
      cells with IFNalpha in combination with an inhibitor of MDM2, Nutlin-3a,
      synergistically affects the proliferation of cancer cells. Importantly, Nutlin-3a
      was able to reduce the effective dose of IFNalpha about 3.4 times. Strikingly,
      this phenomenon is p53-independent, because H1299 cells lack p53, but is highly
      dependent on MDM2 because its ablation makes tumor cells completely insensitive
      to IFNalpha alone or in combination with Nutlin-3a. On the contrary,
      overexpression of MDM2 makes H1299 cells more susceptible to both IFNalpha and
      IFNalpha/Nutlin-3a treatments. Mechanistically, treatment with combination of
      IFNalpha and Nutlin-3a attenuates cyclin D1/CDK4 on the protein level and hence
      blocks cell cycle progression. This mechanism may be responsible, at least in
      part, for the anti-proliferative effects on H1299 cells observed. Our data
      suggest that the expression of MDM2 confers sensitivity of cancer cells to
      IFNalpha/Nutlin-3a treatment. Moreover, our data also confirm positive effect of
      Nutlin even on p53-deficient neoplasms.

PMID- 29175212
TI  - Role of pyroptosis in normal cardiac response to calorie restriction and
      starvation.
AB  - AIMS: An unhealthy diet is a major risk factor for cardiac diseases. Most
      researches focus on high fat diet, little is known about the detrimental effects
      of starvation on heart. METHODS: Mice were fed 100%, 40% and 20% of ad libitum to
      mimic the situation of moderate and severe caloric restriction (CR). To further
      evaluate the different effect of CR and starvation on cardiomyocyte, AC16 cells
      were treated with different concentrations of serum or glucose. TUNEL staining
      was performed to evaluate DNA damage in AC16 cells. HE and Masson staining were
      performed to detect the morphology and degree of fibrosis in myocardium from
      mice. Immunohistochemical staining, immunofluorescence staining, western blot and
      real-time PCR were used to detect the protein and mRNA expression of caspase-1,
      IL-1beta and IL-18. RESULTS: CR and starvation decrease body weight of mice in a
      concentration dependent manner. The starvation group showed a remarkable
      myocardial fibrosis with no significant alteration between control and CR groups.
      CR inhibited the activation of caspase-1 as well as the expression of IL-1beta
      and IL-18. On the contrary, starvation plays completely opposite effects, which
      was in accordance with histological changes. Similarly, different levels of serum
      and glucose deprivation were used to mimic the effect of CR and starvation in
      vitro. Moderate level of serum and glucose deprivation exerts protective effect
      on AC16 cells through the inhibition of pyroptosis, whereas high level of serum
      and glucose deprivation induces cell injury through the induction of pyroptosis.
      CONCLUSION: CR alleviates pyroptosis, whereas starvation promotes the progression
      of pyroptosis in myocardial tissues and cells.

PMID- 29175213
TI  - A new therapeutic proposal for inoperable osteosarcoma: Photodynamic therapy.
AB  - BACKGROUND: Osteosarcoma, a malignant tumor characterized by bone or osteoid
      formation, is the second most common primary bone neoplasm. Clinical symptoms
      include local and surrounding pain, unrelieved by rest or anesthesia.
      Osteosarcoma has a poor chemotherapeutic response with prognosis dependent on
      complete tumor excision. Therefore, for inoperable osteosarcoma new therapeutic
      strategies are needed. The present study aimed to develop murine models of
      cranial and vertebral osteosarcoma that facilitate simple clinical monitoring and
      real-time imaging to evaluate the outcome of photodynamic therapy based on a
      previously developed photosensitizer. METHODS: Balb/c nude mice were divided into
      two groups: the cranial and vertebral osteosarcoma groups. Each group was further
      subdivided into the photodynamic therapy-treated and untreated groups. Images
      were obtained by scintigraphy with 99mTc-MIBI and radiography. Tumor growth,
      necrotic area, osteoid matrix area, and inflammatory infiltration were analyzed.
      RESULTS: Cranial and vertebral tumors could be macroscopically observed and
      measured. Radiographic and scintigraphic images showed tumor cells present at the
      inoculation sites. After photodynamic therapy, scintigraphy showed lower tumoral
      radiopharmaceutical uptake, which correlated histologically with increased
      necrosis. Osteoid matrix volume increased, and tumor size decreased in all
      photodynamic therapy-treated animals. CONCLUSION: Cranial and vertebral
      osteosarcoma models in athymic mice are feasible and facilitate in vivo
      monitoring for the development of new therapies. Photodynamic therapy is a
      potential antitumoral treatment for surgically inoperable osteosarcoma.

PMID- 29175214
TI  - Survival in patients with primary dermatofibrosarcoma protuberans: National
      Cancer Database analysis.
AB  - BACKGROUND: The predictors of mortality, second surgery, and postoperative
      radiation therapy for treating dermatofibrosarcoma protuberans (DFSP) are not
      well described. OBJECTIVE: We sought to determine the impact of patient
      demographics, tumor characteristics, and treatment site and modality on survival
      after primary DFSP. METHODS: A retrospective analysis of data from the National
      Cancer Database was performed for patients diagnosed with DFSP during 2003-2012.
      RESULTS: A total of 5249 cases were identified. Of these, 3.1% of patients died
      during an average of 51.4 months of follow-up. After adjusting for relevant
      factors, lack of insurance, Medicaid and Medicare insurance, anaplastic
      histology, and positive postoperative margins all predicted mortality, while
      treatment at an Integrated Network Cancer Program predicted survival (P < .05).
      Higher odds of postoperative radiation therapy were directly associated with
      large tumor size, anaplastic and poorly differentiated histology, and positive
      postoperative margins and inversely associated with treatment at high volume
      facilities, and non-head and neck tumors. Higher second surgery rates were
      associated with Hispanic ethnicity, and lower rates were associated with female
      sex. LIMITATIONS: Survival data was not cancer-specific. CONCLUSION: Better
      understanding of factors affecting survival outcomes might help improve
      management of DFSP and delineate other potential causes of increased morbidity
      and mortality.

PMID- 29175215
TI  - PdPt nanoparticles anchored on the N-G with the integration of PANI nanohybrids
      as novel redox probe and catalyst for the detection of rs1801177.
AB  - Single nucleotide polymorphism (SNP) in lipoprotein lipase (LPL) gene (rs1801177)
      is strongly associated with the increased progression of atherosclerosis,
      threatening global public health. In this work, a relatively simple, specific and
      ultrasensitive electrochemical DNA biosensor was constructed to detect rs1801177
      for the first time. A glass carbon electrode was modified with fullerene
      (C60)/polyamidoamine (PAMAM)/gold (Au) nanoparticles nanocomposites film. In
      addition the nitrogen-doped graphene (N-G)/palladium platinum (PdPt) bimetallic
      nanoparticle/ polyaniline (PANI) nanohybrids were synthesised and used to label
      the signal probes. These nanohybrids have abundant active groups, and efficient
      redox and catalytic activity, allowing them to be used as the nanocarrier for a
      redox nanoprobe without the additional modification of electroactive substance
      and catalyst, which could effectively simplify the operation procedure and
      shorten the analysis time. With the catalysis of H2O2 by nanohybrids, the
      detection signal of N-G/PdPt/PANI itself could be significantly enhanced, lead to
      the improvement of the sensitivity. Under optimal conditions, the electrochemical
      DNA biosensor exhibited desirable performance for the determination of rs1801177
      with a wide linearity ranging from 10 fM to 10nM and a relatively low detection
      limit of 3.33 fM (S/N=3). The proposed biosensor showed excellent selectivity to
      the target DNA compared to possible interfering substances. The results suggested
      that this method has potential applications in clinical research.

PMID- 29175216
TI  - Ultrasensitive electrochemiluminescence assay of tumor cells and evaluation of
      H2O2 on a paper-based closed-bipolar electrode by in-situ hybridization chain
      reaction amplification.
AB  - In this manuscript, a disposable paper-based analytical device comprised of a
      closed bipolar electrode (BPE) was fabricated for the ultrasensitive
      electrochemiluminescence (ECL) detection of intracellular H2O2 and the number of
      cancer cells. In this approach, wax printing was used to fabricated reaction
      zone, and carbon ink-based BPE and driving electrodes were screen-printed into
      the paper. AuPd nanoparticles (NPs), which served as a carrier of the capture
      aptamer and as the catalyst for the ECL reaction of luminol and H2O2, were used
      to modify the BPE. Luminol/Au NPs were attached to the surface of the captured
      cells via hybridation chain reaction with two hairpin structure DNA labelled
      luminol/Au NPs. In the stimulation of phorbol myristate acetate, The coreactant
      H2O2 was released from the target cells. The ECL response of the luminol-H2O2
      system was related to the number of cancer cells in the testing buffer, which
      served as a quantitative signal for the determination of cancer cells and the
      concentration of H2O2. In order to decrease the external voltage, K3[Fe(CN)6] was
      introduced in the cathode resevoir of BPE because it gained electrons at the
      cathode more easily than oxygen. The ECL intensity was quantitatively related to
      the concentration of MCF-7 in the range of 1.0 * 102-1.0 * 107 cells/mL. The
      detection limit was 40 cells/mL and it showed good specificity for cells with
      high overexpression of mucin-1 receptor, it was concluded that the developed
      protocol could be effectively utilized for the detection of MCF-7 cells.

PMID- 29175217
TI  - Superwettable microchips with improved spot homogeneity toward sensitive
      biosensing.
AB  - The high-quality spots in microchips are prerequisites for sensitive and accurate
      detection of biomarkers. In this work, the superwettable micropattern was
      constructed by introducing superhydrophilic microwells onto a superhydrophobic
      substrate. The sample can distribute homogeneously within the well-designed
      superhydrophilic microwells after droplet evaporation and form homogeneous
      deposit spots, which can be ascribed to the enhanced Marangoni effect in
      superwettable micropattern and the suppressed outward flow by 3D nanodendritic
      silica structure. Based on the improved homogeneity of spots, sensitive and
      accurate fluorescence readout could be obtained. The free prostate-specific
      antigen (f-PSA) microchip based on the superwettable micropattern was developed.
      This superwettable f-PSA microchip exhibits high sensitivity, excellent
      specificity and long-term stability, and a limit of detection as low as 10fgmL-1
      is achieved. Moreover, the superwettable f-PSA microchip can accurately detect
      human serum samples with excellent correlations with chemiluminescence
      immunoassay in the clinic, demonstrating its great potential as a sensitive and
      reliable sensing platform for biological analysis and clinical diagnosis.

PMID- 29175218
TI  - A multi-functional gold/iron-oxide nanoparticle-CNT hybrid nanomaterial as virus
      DNA sensing platform.
AB  - Nanoparticle (NP)-carbon nanomaterial hybrid structures have garnered significant
      attention due to their synergistic effects. Based on their interesting
      properties, hybrid nanomaterial-based sensing platforms have been investigated to
      achieve high sensitivity and selectivity detection. In our study, binary-NP
      decorated carbon nanotubes (bNP-CNTs) were successfully synthesized through a
      simple two-step method and applied as a biosensing platform. Gold (Au)/iron-oxide
      magnetic NP-decorated CNTs (Au/MNP-CNT) were used for influenza and norovirus DNA
      sensing channels. To demonstrate biosensing, first, the Au/MNP-CNTs were
      magnetically aligned on a Pt-interdigitated electrode, and then, a thiol-group
      functionalized probe DNA was attached to the Au NP surface on the bNP-CNT hybrid
      structure through thiol chemistry. DNA hybridization between the target influenza
      or norovirus DNA and probe DNA was measured to monitor an electrical conductivity
      change of the Au/MNP-CNTs. Various concentrations of target DNA from 1pM to 10nM
      were monitored, and the limits of detection for influenza virus and norovirus
      were calculated to be approximately 8.4pM and 8.8pM, respectively. The
      specificity was confirmed using different mismatched DNA sequences, showing high
      specificity. Therefore, this Au/MNP-CNT-based DNA sensing system exhibited
      excellent detection potential, and such hybrid materials could be universally
      applied as a highly sensitive and selective biosensing system.

PMID- 29175219
TI  - Effects of religiosity and religious coping on medication adherence and quality
      of life among people with epilepsy.
AB  - The epidemiologic information demonstrates the importance of caring people with
      epilepsy (PWE). Indeed, the impaired quality of life (QoL) and medication
      nonadherence rate among PWE have been reported. However, religiosity and
      religious coping could be potential factors for clinicians to foster appropriate
      intervention on epileptic care. This study investigated two models to further
      understand the relationships between religiosity, religious coping (including
      positive and negative coping), medication adherence, and QoL in an Iranian sample
      with epilepsy. Eligible PWE (n=760) completed the religiosity scale (Duke
      University Religion Index; DUREL) at baseline; the religious coping scale (Brief
      Religious Coping Scale; Brief RCOPE) one month later; the medication adherence
      scale (Medication Adherence Report Scale; MARS-5) two months later; and the QoL
      scale (Quality of Life in Epilepsy; QOLIE-31) twelve months later. Their
      antiepileptic drug serum level was measured during the period they completed the
      MARS. Through structural equation modeling (SEM), we found that religiosity
      directly correlated with negative religious coping and medication adherence, and
      indirectly correlated with medication adherence through negative religious
      coping. Both positive and negative religious coping directly correlated with
      medication adherence and QoL. Therefore, religiosity and religious coping may be
      determinants of medication adherence and QoL in PWE; health professionals may
      consider asking PWE if religion is important to them and how they use it to cope
      with their epilepsy.

PMID- 29175220
TI  - Periictal sign of the cross or Signum Crucis as a lateralizing sign in focal
      epilepsies: Not only a right temporal lobe epilepsy feature.
AB  - INTRODUCTION: The sign of the cross (SC) is a catholic ritual that has been
      described as an automatism during the ictal phase in patients with right temporal
      lobe epilepsy. OBJECTIVE: The study aimed to describe the prevalence of the SC
      and analyze the characteristics of patients who presented this phenomenon during
      the video-electroencephalography (VEEG) admission in our Epilepsy department.
      METHODS: This is a retrospective analysis of 1308 recorded seizures; 14 patients
      presented the SC during the admission. Seizure semiology, electroencephalography
      (EEG), etiology, neuroimaging, and surgical findings were analyzed. RESULTS: A
      prevalence of 1.1% was found, and the sign was not only an ictal finding (21% was
      postictal) but also exclusive of patients with temporal lobe epilepsy (15% were
      extratemporal) in contrast to what has been reported so far. The localizing and
      lateralizing value of the ictal SC was low (sensitivity 75%, specificity 33.3%,
      positive predictive value 60%, negative predictive value 50% for a right temporal
      epileptogenic zone (EZ)) compared with other previously described signs.
      Regardless of the lateralization of the EZ, the sign was always performed with
      the right hand supporting the hypothesis of a possible learned behavioral
      automatism. CONCLUSION: The SC is a rare ictal or postictal manifestation that
      occurs in patients with temporal and extratemporal epilepsies without clear
      localizing and lateralizing value compared with previously described signs.

PMID- 29175221
TI  - Epilepsy is a neurological and a systemic disorder.
AB  - The basic pathophysiology of epilepsy is still not fully understood.
      Epidemiological evidence for epilepsy seems to suggest that it may not only be
      the propensity for seizures to occur. The high prevalence of comorbidity and the
      finding that premature mortality is still increased in those who are in long-term
      remission, suggest that there is a systemic component to the condition. This
      systemic component is an additional shared risk factor that can explain an
      important proportion of the comorbidities of epilepsy as well as how an
      individual with inactive epilepsy remains at an elevated risk of premature
      mortality. This systemic component can be viewed from the perspective of a number
      of fundamental pathophysiological processes: inflammation, oxidative stress,
      glycation, and methylation capacity. These processes are associated with all
      cause mortality and there is also a growing understanding of their impact on
      seizure processes. We propose that epilepsy be considered as the sum of seizures
      and comorbidities caused by systemic dysfunction, and that the comprehensive
      management of epilepsy should also include the management of the systemic
      dysfunction.

PMID- 29175222
TI  - Temporal lobe asymmetry in FDG-PET uptake predicts neuropsychological and seizure
      outcomes after temporal lobectomy.
AB  - OBJECTIVE: The objective of this study was to determine whether preoperative
      [18F]fludeoxyglucose (FDG)-positron emission tomography (PET) asymmetry in
      temporal lobe metabolism predicts neuropsychological and seizure outcomes after
      temporal lobectomy (TL). METHODS: An archival sample of 47 adults with unilateral
      temporal lobe epilepsy who underwent TL of their language-dominant (29 left, 1
      right) or nondominant (17 right) hemisphere were administered neuropsychological
      measures pre- and postoperatively. Post-TL seizure outcomes were measured at
      1year. Regional FDG uptake values were defined by an automated technique, and a
      quantitative asymmetry index (AI) was calculated to represent the relative
      difference in the FDG uptake in the epileptic relative to the nonepileptic
      temporal lobe for four regions of interest: medial anterior temporal (MAT),
      lateral anterior temporal (LAT), medial posterior temporal (MPT), and lateral
      posterior temporal (LPT) cortices. RESULTS: In language-dominant TL, naming
      outcomes were predicted by FDG uptake asymmetry in the MAT (r=-0.38) and LPT (r=
      0.45) regions. For all patients, visual search and motor speed outcomes were
      predicted by FDG uptake asymmetry in all temporal regions (MPT, r=0.42; MAT,
      r=0.34; LPT, r=0.47; LAT, r=0.51). Seizure outcomes were predicted by FDG uptake
      asymmetry in the MAT (r=0.36) and MPT (r=0.30) regions. In all of these
      significant associations, greater hypometabolism in regions of the epileptic
      temporal lobe was associated with better postoperative outcomes. CONCLUSIONS: Our
      results support the conclusion that FDG uptake asymmetry is a useful clinical
      tool in assessing risk for cognitive changes in patients being considered for TL.

PMID- 29175223
TI  - Implementation of a Mindfulness Moment Initiative for Healthcare Professionals:
      Perceptions of Facilitators.
AB  - CONTEXT: Mindfulness practices in the workplace have experienced rapid growth,
      with initial evidence suggesting positive outcomes. Even so, little is known
      about implementing mindfulness-based interventions (MBI), especially internally
      driven programs led by volunteers rather than experts. OBJECTIVE: This study
      qualitatively explores volunteer facilitators' perceptions of a short-dose MBI
      (the mindfulness moment initiative) before and 6 weeks after implementation.
      METHODS: Mindfulness moments were 1-3-minute-guided periods of mindfulness led at
      the beginning of various staff meetings at an inner-city community medical
      center. Facilitators' perceptions were collected through thirty-one 30-minute
      semi-structured interviews before and after the MMI's first 6 weeks. Categorizing
      and connecting strategies were employed to explore the emergence of themes and
      patterns across responses. RESULTS: Mindfulness moment facilitators interviewed
      before the intervention expected their groups to experience several intra- and
      interpersonal benefits. After implementation, they perceived all of these
      benefits to have occurred, but some benefits were mentioned more frequently
      before than after implementation and vice versa. Five of six expected obstacles
      were reported after implementation, with timing issues emerging as the most
      frequently mentioned theme. Facilitators believed that benefits outweighed
      obstacles. Our data also suggested that mindfulness moments may provide managers
      with an additional way to address moments of tension occurring between co
      workers. Most facilitators intended to continue leading mindfulness moments and
      wished to expand the practice to new departments. CONCLUSION: The mindfulness
      moment intervention may provide a way to bring mindfulness into organizations
      that is not dependent on formal training programs, a large time commitment, or a
      commitment to extended training. Prior knowledge of the obstacles and benefits
      found here may result in a more successful intervention.

PMID- 29175224
TI  - The Shock of Charlottesville: Unmasking Racism in Healthcare.

PMID- 29175225
TI  - 'Pastoral practices' for quality improvement in a Kenyan clinical network.
AB  - We explain social and organisational processes influencing health professionals
      in a Kenyan clinical network to implement a form of quality improvement (QI) into
      clinical practice, using the concept of 'pastoral practices'. Our qualitative
      empirical case study, conducted in 2015-16, shows the way practices constructing
      and linking local evidence-based guidelines and data collection processes
      provided a foundation for QI. Participation in these constructive practices gave
      network leaders pastoral status to then inscribe use of evidence and data into
      routine care, through championing, demonstrating, supporting and mentoring, with
      the support of a constellation of local champions. By arranging network meetings,
      in which the professional community discussed evidence, data, QI and
      professionalism, network leaders also facilitated the reconstruction of network
      members' collective professional identity. This consequently strengthened top
      down and lateral accountability and inspection practices, disciplining evidence
      and audit-based QI in local hospitals. By explaining pastoral practices in this
      way and setting, we contribute to theory about governmentality in health care and
      extend Foucauldian analysis of QI, clinical networks and governance into low and
      middle income health care contexts.

PMID- 29175226
TI  - What if the baby doesn't survive? Health-care decision making for ill newborns in
      Ethiopia.
AB  - Despite efforts to improve access to and quality of care for newborns, the first
      month after birth remains the most dangerous period of life. Given high neonatal
      mortality in low-income countries, saving newborn lives is a key priority for
      global and national health policy agendas. However, little is known about how
      these policies resonate with local understandings, experiences and household
      priorities. In this qualitative study we examined families' decision making and
      health-care-seeking in Butajira, Ethiopia. Data were collected through
      observation in hospital, in-depth interviews (41), and focus group discussions
      (7) with family members, health-care workers, and community members (October
      November 2015). Transcripts and field notes were analyzed inductively using
      qualitative content analysis. Findings indicate that newborn health was not
      always the family's priority. Local perceptions of newborns as not yet useful
      members of the household alongside costly health-care services delayed decision
      making and care-seeking. While sickness was recognized as dangerous for the ill
      newborn, seeking health-care could be harmful for the economic survival of the
      family. In a resource-constrained setting, families' focused on productive assets
      in order to minimize long-term risks, and waited before seeking newborn health
      care services. Until the baby had survived the first vulnerable weeks and months
      of life, the unknown newborn was not yet seen as a social person by the
      community. Personhood evolved progressively as the baby became a part of the
      family. A newborn death was surrounded by silence, and families received minimal
      support from traditional financial associations, iddirs. Decisions regarding
      health-care were contingent upon families' understandings of newborns and their
      resource-constrained circumstances. Improving newborn health involves recognizing
      why families choose to (not) seek health-care, and their actual opportunities and
      constraints in making such decisions. The everyday realities of vulnerable
      newborns must be at the center of global and national policy discussions and
      local implementation.

PMID- 29175227
TI  - Does Testosterone Treatment Increase Anger Expression in a Population of
      Transgender Men?
AB  - BACKGROUND: The acquisition of phenotypic male features in transmen with gender
      dysphoria requires testosterone treatment. The suppression of menses is 1 of the
      most desired effects. The relation between testosterone levels and human
      aggressive behavior has been described. However, the effects of testosterone on
      anger expression have been poorly investigated in trans-persons. AIM: To assess
      the effects of testosterone treatment on anger expression in transmen using a
      validated self-report questionnaire (Spielberger's State-Trait Anger Expression
      Inventory-2 [STAXI-2]). METHODS: 52 transmen diagnosed with gender dysphoria were
      evaluated before (T0) and at least 7 months after (T1) initiation of continuous
      gender-affirming testosterone treatment. Sociodemographic characteristics,
      anthropometric parameters, diagnosis of psychiatric disorders, current
      psychopharmacologic treatments, and life events were investigated at T0.
      OUTCOMES: STAXI-2 scores, serum testosterone, and estradiol levels at T0 and T1
      were compared. RESULTS: Most of the sample (61.5%, n = 32) had no Axis I or II
      comorbidity. All subjects at T1 achieved significantly higher serum testosterone
      levels (5.67 +/- 3.88 ng/mL), whereas no significant difference in estradiol
      levels was observed from T0 to T1. At T1 only 46.2% (n = 24) of the sample
      achieved iatrogenic amenorrhea, whereas most of the sample had persistent regular
      bleedings. A significant increase in STAXI anger expression and anger control
      scores from T0 to T1 was recorded. Patients with persistent bleedings and Axis I
      disorders seemed to have higher odds of expressing anger. However, circulating
      testosterone levels at T1 did not influence anger expression. CLINICAL
      IMPLICATIONS: Interestingly, despite the increase of anger expression scores,
      during continuous testosterone treatment, there were no reports of aggressive
      behavior, self-harm, or psychiatric hospitalization. STRENGTHS AND LIMITATIONS: A
      limitation to this study is that although the STAXI-2 is a well-validated
      instrument measuring anger expression, it is a self-report psychometric measure.
      CONCLUSION: This study demonstrates that during 7 months of continuous gender
      affirming hormonal treatment, anger expression and anger arousal control
      increased in transmen. Persistence of menstrual bleedings and Axis I disorders,
      but not circulating testosterone levels, were predictive of the increase in anger
      expression score. Continuous psychological support to transmen during gender
      affirming hormonal treatment was useful to prevent angry behaviors and decrease
      the level of dysphoria. Motta G, Crespi C, Mineccia V, et al. Does Testosterone
      Treatment Increase Anger Expression in a Population of Transgender Men? J Sex Med
      2018;15:94-101.

PMID- 29175229
TI  - Systematic review of mental health measures associated with concussive and
      subconcussive head trauma in former athletes.
AB  - Public concern has been a catalyst for an emerging body of research investigating
      the potential long-term negative health consequences associated with sport
      related concussion and subconcussive impacts. We conducted a systematic review of
      the literature on mental health measures associated with sport-related brain
      injuries in former athletes. Ovid MEDLINE, EMBASE, CINAHL, and PsychINFO
      databases were used. Thirteen studies were included in the final review. We
      identified a consistent positive association between a history of concussion and
      depression among former athletes, although the underlying causation remains
      unclear. Limited and inconsistent findings were observed in studies that
      evaluated subconcussive impacts. Overall, several methodological shortcomings
      were noted, including selection bias, research design, operational definitions,
      and measurement tools. Future research will benefit from employing prospective
      longitudinal studies, surveillance data systems and standardized collection
      methods, and should attempt to account for psychosocial modifiers or confounders
      when reporting the mental health status of former athletes. This area would also
      benefit from studies that include equal representation of male and female
      athletes, examine mental health disorders beyond depression, and assess a variety
      of sports and competition levels.

PMID- 29175228
TI  - Porous silicon based photoluminescence immunosensor for rapid and highly
      sensitive detection of Ochratoxin A.
AB  - A rapid and low cost photoluminescence (PL) immunosensor for the determination of
      low concentrations of Ochratoxin A (OTA) has been developed. This immunosensor
      was based on porous silicon (PSi) and modified by antibodies against OTA (anti
      OTA). PSi layer was fabricated by metal-assisted chemical etching (MACE)
      procedure. Main structural parameters (pore size, layer thickness, morphology and
      nanograins size) and composition of PSi were investigated by means of X-Ray
      diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy. PL
      spectroscopy of PSi was performed at room temperature and showed a wide emission
      band centered at 680 +/- 20nm. Protein A was covalently immobilized on the
      surface of PSi, which in next steps was modified by anti-OTA and BSA in this way
      a anti-OTA/Protein-A/PSi structure sensitive towards OTA was designed. The anti
      OTA/Protein-A/PSi-based immunosensors were tested in a wide range of OTA
      concentrations from 0.001 upto 100ng/ml. Interaction of OTA with anti-OTA/Protein
      A/PSi surface resulted in the quenching of photoluminescence in comparison to
      bare PSi. The limit of detection (LOD) and the sensitivity range of anti
      OTA/Protein-A/PSi immunosensors were estimated. Association constant and Gibbs
      free energy for the interaction of anti-OTA/Protein-A/PSi with OTA were
      calculated and analyzed using the interaction isotherms. Response time of the
      anti-OTA/Protein-A/PSi-based immunosensor toward OTA was in the range of 500
      700s. These findings are very promising for the development of highly sensitive,
      and potentially portable immunosensors suitable for fast determination of OTA in
      food and beverages.

PMID- 29175230
TI  - Respiratory syncytial virus A in haematological patients with prolonged shedding:
      Premature stop codons and deletion of the genotype ON1 72-nucleotide-duplication
      in the attachment G gene.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) can be associated with severe
      disease and prolonged shedding in immunocompromised patients. OBJECTIVE: To
      investigate the genetic variability of RSV in consecutive samples of
      haematological patients with prolonged RSV shedding. STUDY DESIGN: Haematological
      patients at the University Hospital Heidelberg are routinely screened for
      respiratory viruses during winter season. In patients with prolonged RSV shedding
      between 2011 and 2014, Sanger-sequencing of the second hypervariable region of
      the RSV G gene was performed in consecutive samples. Further, deep-sequencing was
      performed in representative samples. RESULTS: Patients with prolonged RSV-A
      shedding were analysed (n=16, mean shedding 90days, 81.2% male). Phylogenetic
      analysis identified RSV genotypes NA1 (2011/12) or ON1 (2012/13). In most
      patients (n=12/16), Sanger-sequencing of the G gene showed identical sequences
      over the course of the shedding period. However, in two patients with
      particularly long viral shedding (333 and 142days), Sanger-sequencing revealed
      the presence of mutations leading to premature stop codons (37 and 70 amino acids
      truncated) in the G gene. In one additional patient, deep-sequencing revealed
      variants with premature stop codons at different positions. All three patients
      received repeatedly intravenous immunoglobulins. Interestingly, deep-sequencing
      revealed also a loss of the characteristic 72-nucleotide-duplication in all
      analysed ON1 strains. CONCLUSIONS: Long shedding periods and lack of immune
      selective pressure in the immunocompromised host seems to allow the persistence
      of viruses stripping a part of the C-terminus of the G glycoprotein. The loss of
      the characteristic 72-nucleotide-duplication in RSV-A ON1 variant strains is here
      described for the first time.

PMID- 29175232
TI  - Cardiovascular complications in patients with Zika virus-induced Guillain-Barre
      syndrome.

PMID- 29175231
TI  - Field performance of the Determine HBsAg point-of-care test for diagnosis of
      hepatitis B virus co-infection among HIV patients in Zambia.
AB  - BACKGROUND: We evaluated the field performance of a rapid point-of-care (POC)
      test for hepatitis B surface antigen (HBsAg) that could support decentralization
      and scale-up of hepatitis B virus (HBV) diagnosis in Africa. OBJECTIVE: To
      determine the field performance of the Determine HBsAg POC test for diagnosis of
      HBV co-infection among HIV patients in Zambia. STUDY DESIGN: Between 2013-2014,
      we screened HIV-infected adults for HBsAg at two urban clinics in Zambia. A
      subset were tested with the POC Determine HBsAg (Alere, USA) by finger prick in
      the clinic and HBsAg serology (Access2Analyzer, Beckman Coulter) at a reference
      laboratory. If either test was reactive, we determined HBV viral load (VL) and
      genotype. We described patient demographic and clinical characteristics
      (including liver fibrosis) and assessed the sensitivity, specificity, positive
      and negative predictive values (PPV and NPV) of the Determine test. In secondary
      analyses, we assessed sensitivity among patients with replicating HBV (i.e.,
      VL>20 IU/ml) and with high HBV VL (i.e.,>20,000IU/ml). RESULTS: Among 412
      participants with both HBsAg tests, median age was 34 years, 51% were women, and
      median CD4 was 208 cells/mm3. By serology, 66 (16%) were HBsAg-positive. Overall
      Determine had 87.9% sensitivity, 99.7% specificity, 98.3% PPV, and 97.7% NPV. Six
      of 8 patients with false negative results had undetectable HBV VL and no evidence
      of significant liver fibrosis. Test sensitivity was 95.9% among the 51 with
      replicating HBV and 100% among the 28 with high HBV VL. CONCLUSIONS: Determine
      HBsAg is a cheaper alternative HBV testing option compared to the gold standard
      ELISA and has high specificity and good sensitivity in the field among HIV
      infected individuals.

PMID- 29175233
TI  - Biological information systems: Evolution as cognition-based information
      management.
AB  - An alternative biological synthesis is presented that conceptualizes evolutionary
      biology as an epiphenomenon of integrated self-referential information
      management. Since all biological information has inherent ambiguity, the
      systematic assessment of information is required by living organisms to maintain
      self-identity and homeostatic equipoise in confrontation with environmental
      challenges. Through their self-referential attachment to information space, cells
      are the cornerstone of biological action. That individualized assessment of
      information space permits self-referential, self-organizing niche construction.
      That deployment of information and its subsequent selection enacted the dominant
      stable unicellular informational architectures whose biological expressions are
      the prokaryotic, archaeal, and eukaryotic unicellular forms. Multicellularity
      represents the collective appraisal of equivocal environmental information
      through a shared information space. This concerted action can be viewed as
      systematized information management to improve information quality for the
      maintenance of preferred homeostatic boundaries among the varied participants.
      When reiterated in successive scales, this same collaborative exchange of
      information yields macroscopic organisms as obligatory multicellular holobionts.
      Cognition-Based Evolution (CBE) upholds that assessment of information precedes
      biological action, and the deployment of information through integrative self
      referential niche construction and natural cellular engineering antecedes
      selection. Therefore, evolutionary biology can be framed as a complex
      reciprocating interactome that consists of the assessment, communication,
      deployment and management of information by self-referential organisms at
      multiple scales in continuous confrontation with environmental stresses.

PMID- 29175234
TI  - Editorial Comment.

PMID- 29175235
TI  - Editorial Comment.

PMID- 29175236
TI  - Predatory Publishing: What Are the Alternatives to Beall's List?

PMID- 29175237
TI  - Severity of Gastrointestinal Bleeding in Patients Treated with Direct-Acting Oral
      Anticoagulants.
AB  - BACKGROUND: Direct-acting oral anticoagulants (DOACs), which have gained approval
      for stroke prevention in nonvalvular atrial fibrillation and treatment of venous
      thromboembolism, have become increasingly preferred over warfarin given their
      predictable pharmacodynamics, lack of required monitoring, and superior outcomes.
      Direct-acting oral anticoagulants have been shown to be associated with an
      increased frequency of gastrointestinal bleeding compared with warfarin, but the
      severity and characteristics of gastrointestinal bleeding in these patients is
      poorly understood. METHODS: We retrospectively evaluated electronic medical
      records of patients with gastrointestinal bleeding (n = 8496) from 2010-2016. We
      identified 61 patients with gastrointestinal bleeding episodes while treated with
      DOACs (rivaroxaban, dabigatran, or apixaban) and 123 patients with
      gastrointestinal bleeding while taking warfarin. We randomly selected a control
      group of 296 patients with gastrointestinal bleeding who were not receiving
      anticoagulation treatment from the same sample. Outcomes included the need for
      hospitalization, blood transfusion, endoscopic or surgical intervention, and 30
      day mortality. RESULTS: The DOAC and warfarin groups were similar in terms of age
      and underlying comorbidity (assessed using the Charlson Comorbidity Index), but
      the DOAC group had greater concomitant aspirin use. Gastrointestinal bleeding was
      classified as upper (n = 186), lower (n = 88), anorectal (n = 183), small bowel
      (n = 9), and indeterminate (n = 14). After adjusting for differences in baseline
      variables, the DOAC group had fewer hospitalizations and required fewer
      transfusions than the warfarin group. The DOAC and control groups were not
      statistically different for all outcomes. There were no significant mortality
      differences among groups. CONCLUSION: Although prior studies have shown a higher
      frequency of gastrointestinal bleeding in patients treated with DOACs compared
      with warfarin, our data suggest that gastrointestinal bleeding in patients taking
      DOACs may be less severe. These differences occurred despite significantly
      greater concomitant aspirin use in the DOAC group compared with warfarin users.

PMID- 29175238
TI  - Which Patent Foramen Ovales Need Closure to Prevent Cryptogenic Strokes?
AB  - Patients with cryptogenic strokes are more likely to have a patent foremen ovale
      than in the general population. It is speculated that these strokes are due to
      paradoxical embolism, that is, passage of a venous thrombus across the patent
      foremen ovale to enter the arterial circulation, resulting in an embolic stroke.
      Venous thromboembolism is rarely present in these cases of cryptogenic stroke.
      Thousands of patients with cryptogenic strokes have undergone transcatheter
      closure of their patent foremen ovale via a variety of devices. The first 3
      randomized clinical trials comparing patent foremen ovale closure with medical
      therapy failed to show a significant advantage of patent foremen ovale closure.
      Three additional trials reported in 2017 had longer years of follow-up and
      demonstrated an advantage of patent foremen ovale closure versus medical therapy.
      Analysis of their data indicated that patent foremen ovale closure in patients
      with an atrial septal aneurysm in addition to a patent foremen ovale had a very
      significant decrease in cryptogenic strokes (P < .001). There was no decrease in
      strokes in patients without an aneurysm of the atrial septum who underwent patent
      foremen ovale closure (P = .37). Aneurysms of the atrial septum are easily
      recognized by echocardiography and are present in approximately one-third of
      patients with patent foremen ovales. These data suggest that closure of patent
      foremen ovales in patients with an atrial septal aneurysm is indicated. In
      patients with a patent foremen ovale without an aneurysm of the atrial septum,
      patent foremen ovale closure is not indicated.

PMID- 29175239
TI  - An Unusual Cause of Exercise-Induced Acute Kidney Injury.

PMID- 29175240
TI  - Reply to: "Energy drinks and adolescents - A hepatic health hazard?"

PMID- 29175241
TI  - Clinical management of polycystic liver disease.
AB  - In this Grand Rounds article, we present a typical case of a woman with
      polycystic liver disease. This case prompts questions which both patients and
      clinicians may face in clinical practice. This article aims to provide guidance
      to clinicians caring for patients with polycystic liver disease, in relation to
      key recent developments in the field. We discuss the latest advances in our
      understanding of pathophysiology, the natural course of disease, complications,
      as well as existing and potential new treatment options.

PMID- 29175242
TI  - Association of non-alcoholic steatohepatitis with subclinical myocardial
      dysfunction in non-cirrhotic patients.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with
      increased cardiovascular risk. Among categories of NAFLD, hepatic fibrosis is
      most likely to affect mortality. Myocardial function and its energy metabolism
      are tightly linked, which might be altered by an insulin resistant condition such
      as NAFLD. We investigated whether hepatic steatosis and fibrosis were associated
      with myocardial dysfunction relative to myocardial glucose uptake. METHODS: A
      total of 308 patients (190 without NAFLD, 118 with NAFLD) were studied in a
      tertiary care hospital. Myocardial glucose uptake was evaluated at fasted state
      using [18F]-fluorodeoxyglucose-positron emission tomography (18FDG-PET). Hepatic
      steatosis and fibrosis were assessed by transient liver elastography
      (Fibroscan(r)) with controlled attenuation parameter, which quantifies hepatic
      fat and by surrogate indices (fatty liver index and NAFLD fibrosis score).
      Cardiac structure and function were examined by echocardiogram. RESULTS: Compared
      to those without NAFLD, patients with NAFLD had alterations in cardiac
      remodeling, manifested by increased left ventricular mass index, left ventricular
      end-diastolic diameter, and left atrial volume index (all p <0.05). Hepatic
      steatosis was significantly associated with left ventricular filling pressure
      (E/e' ratio), which reflects diastolic dysfunction (p for trend <0.05). Those
      without NAFLD were more likely to have higher myocardial glucose uptake compared
      to those with NAFLD. Significant hepatic fibrosis was also correlated with
      diastolic dysfunction and impaired myocardial glucose uptake. Using multivariable
      linear regression, E/e' ratio was independently associated with hepatic fibrosis
      (standardized beta = 0.12 to 0.27; all p <0.05). Association between hepatic
      steatosis and E/e' ratio was also significant (standardized beta = 0.10 to 0.15;
      all p <0.05 excluding the model adjusted for adiposity). CONCLUSIONS: Hepatic
      steatosis and fibrosis are significantly associated with diastolic heart
      dysfunction. This association is linked with myocardial glucose uptake evaluated
      by 18FDG-PET. LAY SUMMARY: Non-alcoholic fatty liver disease is associated with
      an increased risk of cardiovascular disease. More severe forms of non-alcoholic
      fatty liver disease, where hepatic fibrosis occurs, are linked to increased
      mortality. In this study, we have shown that hepatic steatosis and fibrosis are
      associated with subclinical myocardial dysfunction. This association is linked to
      altered myocardial glucose uptake.

PMID- 29175243
TI  - The molecular functions of hepatocyte nuclear factors - In and beyond the liver.
AB  - The hepatocyte nuclear factors (HNFs) namely HNF1alpha/beta, FOXA1/2/3,
      HNF4alpha/gamma and ONECUT1/2 are expressed in a variety of tissues and organs,
      including the liver, pancreas and kidney. The spatial and temporal manner of HNF
      expression regulates embryonic development and subsequently the development of
      multiple tissues during adulthood. Though the HNFs were initially identified
      individually based on their roles in the liver, numerous studies have now
      revealed that the HNFs cross-regulate one another and exhibit synergistic
      relationships in the regulation of tissue development and function. The complex
      HNF transcriptional regulatory networks have largely been elucidated in rodent
      models, but less so in human biological systems. Several heterozygous mutations
      in these HNFs were found to cause diseases in humans but not in rodents,
      suggesting clear species-specific differences in mutational mechanisms that
      remain to be uncovered. In this review, we compare and contrast the expression
      patterns of the HNFs, the HNF cross-regulatory networks and how these liver
      enriched transcription factors serve multiple functions in the liver and beyond,
      extending our focus to the pancreas and kidney. We also summarise the insights
      gained from both human and rodent studies of mutations in several HNFs that are
      known to lead to different disease conditions.

PMID- 29175244
TI  - Early liver transplantation for alcoholic hepatitis: Ready for primetime?

PMID- 29175245
TI  - Characterization of two channel catfish, Ictalurus punctatus, glucocorticoid
      receptors and expression following an acute stressor.
AB  - Two channel catfish glucocorticoid receptor genes, ipGR1 (NR3C1_1) and ipGR2
      (NR3C1_2) were partially characterized. Identification and analysis of the
      genomic organization of two channel catfish glucocorticoid (GC) receptors (GRs)
      revealed differences in the lengths of exons 1 and 2 and the addition of an extra
      27-bp exon inserted after exon 2 in the GR1 gene, yielding a 9-aa insert in the
      receptor protein. Sequence of the 9-aa insert in ipGR1 (WRARQNTHG) is unique
      compared to other teleost fish GRs. Amino acid sequence alignment of the two
      channel catfish GRs, revealed 55% sequence identity between them, with a high
      degree of sequence conservation (82%) in the DNA binding and ligand binding
      domains. Real-time PCR indicated that ipGR1 and ipGR2 were expressed in all
      tissues evaluated. Channel catfish GR1 was predominantly expressed in the gills,
      nearly 25-fold higher than in the liver. GR1 expression was higher than GR2
      expression in gills, intestine, head kidney and heart (P<0.05). Channel catfish
      hepatic GR1 mRNA expression was significantly (P<0.05) increased from pre-stress
      expression 30min following removal of the acute stressor. After 30min of stress
      and during the 2h recovery period, ipGR1 mRNA expression was higher relative to
      ipGR2 expression. Hepatic ipGR2 expression was not affected (P>0.05) by the acute
      stress event. The present study adds to the growing body of information on GR
      evolution and function and further demonstrates the unique regulation of the
      GC/GR system in teleost fish.

PMID- 29175246
TI  - Reply.

PMID- 29175247
TI  - Reply.

PMID- 29175248
TI  - A data extraction algorithm for assessment of contraceptive counseling and
      provision.
AB  - BACKGROUND: Contraception counseling and provision is an essential preventative
      service. Real-time assessment of these services is critical for quality
      improvement and comparative study. Direct observation is not feasible on a large
      scale, so indirect measures (such as chart review) have been determined to be
      acceptable tools for this assessment. Computer-aided chart review has significant
      benefits over manual chart review as far as greater efficiency and ease of
      repeated measurements. The wide use of electronic medical records provides an
      opportunity to create a data extraction algorithm for computer-aided chart review
      that is sharable among institutions. We provide a useful schema for others who
      use electronic medical record systems and are interested in real-time assessment
      of contraception counseling and provision for the purposes of baseline assessment
      of services and quality improvement. OBJECTIVE: The purpose of this study was to
      create a comprehensive and accurate data extraction algorithm that is useful in
      the assessment of contraception counseling and provision rates in the outpatient
      setting. STUDY DESIGN: We included all visits between August 2015 and May 2016 at
      8 outpatient clinics that are affiliated with a large, urban academic medical
      center in which nonpregnant women who were 14-45 years old were seen by a nurse
      practitioner, physician's assistant, or physician. Contraception-related
      prescriptions, International Classification of Diseases codes, current procedural
      terminology codes, and search-term capture were extracted with the use of
      structured query language from electronic medical record data that were stored in
      a relational database. The algorithm's hierarchy was designed to query
      prescription data first, followed by International Classification of Diseases and
      current procedural terminology codes, and finally search-term capture. Visits
      were censored when the first positive evidence of contraceptive service was
      obtained. Search terms were selected based on group discussion of investigators
      and providers. This algorithm was then compared with manual chart review and
      refined 3 times until high sensitivity and specificity, when compared with manual
      chart review, were achieved. RESULTS: There were 22,134 visits of reproductive
      aged women who our inclusion criteria. Electronic medical record evidence of
      contraception counseling or provision was found in 56.9% of these visits. Of
      these, 21.3% were captured by prescriptions; 8.9% were captured by International
      Classification of Diseases codes, and 69.7% were captured by search-term capture
      with the use of our algorithm. Among visits with evidence of contraception
      counseling without provision, 15.7% were captured by diagnosis codes and 84.3%
      were captured by search-term capture. When compared with manual chart review,
      sensitivity and specificity improved from 0.79 and 0.85 to 0.99 and 0.98,
      respectively, over the 3 rounds of testing and revision. CONCLUSION: Data
      extraction algorithms can be used effectively for computer-aided chart review of
      contraception counseling and provision measures, but testing and refinement are
      extremely important. Search-term capture from unstructured data is a critical
      component of a comprehensive algorithm, especially for the capture of instances
      of contraception counseling without provision. The algorithm that we developed
      here could be used by others with an electronic medical record system who are
      interested in real-time assessment, quality improvement, and comparative study of
      the delivery of contraceptive services. The ease of execution of this algorithm
      also allows for its repeated use for ongoing assessments over time.

PMID- 29175249
TI  - Reply.

PMID- 29175250
TI  - SMFM Special Report: Putting the "M" back in MFM: Addressing education about
      disparities in maternal outcomes and care.
AB  - At the 36th Annual meeting of the Society for Maternal-Fetal Medicine (SMFM),
      leaders in the field of maternal-fetal medicine (MFM) convened to address
      maternal outcome and care inequities from 3 perspectives: (1) education, (2)
      clinical care, and (3) research. Meeting attendees identified knowledge gaps
      regarding disparities within the provider community; reviewed possible frameworks
      to address these knowledge gaps; and identified models with which to address key
      clinical issues. Collaboration and communication between all stakeholders will be
      needed to gain a better understanding of these prevailing disparities and
      formulate strategies to eliminate them.

PMID- 29175251
TI  - Reply.

PMID- 29175252
TI  - Comment on confounding, causality, and confusion.

PMID- 29175253
TI  - Limitations of cohort studies with historic controls.

PMID- 29175254
TI  - Second stage cesarean as risk factor for preterm birth: how to manage subsequent
      pregnancies?

PMID- 29175255
TI  - Reply.

PMID- 29175256
TI  - Progesterone therapy in endometrial cancer.

PMID- 29175257
TI  - Migraine with aura and screening for biological thrombophilia.

PMID- 29175258
TI  - Breastfeeding initiation: An in-depth qualitative analysis of the perspectives of
      women and midwives using Social Cognitive Theory.
AB  - OBJECTIVE: to explore women's and midwives' expectations, knowledge and
      experiences of breastfeeding initiation using Social Cognitive Theory. DESIGN: a
      qualitative study using focus group discussions and individual interviews.
      Breastfeeding initiation was defined for this study as a process within the first
      48hours after birth. Data were analysed using qualitative inductive analysis then
      further deductive analysis using Social Cognitive Theory (SCT). SETTING AND
      PARTICIPANTS: a purposefully selected sample of primigravid antenatal and
      postnatal women (n=18) and practising midwives (n=18) from one Health Board area
      in Scotland. FINDINGS: attachment of the baby to the breast at birth was hindered
      by sleepy babies and the busy unfamiliar hospital environment. These resulted in
      mothers struggling to maintain their motivation to breastfeed and to develop low
      self-efficacy. Instinctive attachment was rare. Midwives who considered it was
      normal for babies to be sleepy and unable to attach or feed at birth did not
      facilitate instinctive baby behaviour. Midwives sometimes experienced lack of
      autonomy and environmental circumstances that made women centred care difficult.
      Furthermore caring for high numbers of women, dependent on their help, resulted
      in reduced self-efficacy for providing effective breastfeeding support. KEY
      CONCLUSIONS: interviewing both women and midwives specifically about initiation
      of breastfeeding has allowed for deeper insights into this critical period and
      enabled a comparison between the data obtained from mothers and midwives. The
      findings suggest that instinctive attachment is not an expectation of either
      mothers or midwives and results in a loss of breastfeeding confidence in both.
      IMPLICATIONS FOR PRACTICE: to facilitate initiation there is a need for more
      research to develop appropriate maternal and midwifery skills, and make changes
      to the cultural environment in hospitals. Social Cognitive Theory could be used
      as a framework in both the antenatal and immediate postnatal period to develop
      strategies and materials to increase women's and midwives' self-efficacy
      specifically in initiation.

PMID- 29175259
TI  - Mechanical properties of milk sphingomyelin bilayer membranes in the gel phase:
      Effects of naturally complex heterogeneity, saturation and acyl chain length
      investigated on liposomes using AFM.
AB  - Sphingomyelin (SM) molecules are major lipid components of plasma membranes that
      are involved in functional domains. Among natural SMs, that found in milk (milk
      SM) exhibits important acyl chain heterogeneities in terms of length and
      saturation, which could affect the biophysical properties and biological
      functions of the milk fat globule membrane or of liposome carriers. In this
      study, the thermotropic and mechanical properties of milk-SM, synthetic C16:0-SM,
      C24:0-SM and the binary mixtures C16:0-SM/C24:0-SM (50:50% mol) and C24:0
      SM/C24:1-SM (95:5% mol) bilayer membranes were investigated using differential
      scanning calorimetry and atomic force microscopy, respectively. Results showed
      that acyl chain length, heterogeneity and unsaturation affected i) the
      temperature of phase transition of SM bilayers, and ii) the mechanical properties
      of liposome (diameter<200nm) membranes in the gel phase, e.g. the Young modulus E
      and the bending rigidity kC. This study increases our knowledge about the key
      role of naturally complex lipid compositions in tailoring the physical properties
      of biological membranes. It could be also used in liposomes development e.g. to
      select the suitable lipid composition according to usage.

PMID- 29175260
TI  - Altered interferon-gamma expression in lymphocytes as a potential peripheral
      marker of chronic stress-induced cognitive deficit.
AB  - It is known that long-term exposure to stressful situations can produce severe
      consequences affecting behavioral, endocrine and immunological parameters. We
      have previously shown that stressed BALB/c mice had poor learning performance,
      which was reverted by glatiramer acetate treatment through a mechanism that
      likely involved the regulation of the cytokine balance and adult neurogenesis. In
      addition, recent results suggest that cytokine and neurotrophin expression in the
      hippocampus displayed similar tendencies as those in the serum. However, if
      lymphoid cells could be good candidates as peripheral markers of memory
      impairment have not yet been investigated. For this purpose, we analyzed the
      spatial memory and the neutrophin and cytokine mRNA levels in lymph nodes and
      hippocampus in mice submitted to chronic stress treated or not with glatiramer
      acetate. Results indicated that there was a correlation between the cytokine and
      neurotrophin mRNA levels in the hippocampus and in the peripheral lymph nodes,
      and the cognitive performance in BALB/c mice. In particular, our results suggest
      that altered IFN-gamma levels could be used as peripheral biomarker of cognitive
      deficit and treatment response.

PMID- 29175261
TI  - Th17 cytokine profiling of colorectal cancer patients with or without enterovirus
      71 antigen expression.
AB  - OBJECT: Th17 cytokines have been identified in several types of human cancers. In
      this pilot study, the expression of Th17 cytokines profiling in enteroviruses 71
      (EV71) associated colorectal cancer (CRC) were explored. METHODS: 66 patients
      with CRC were enrolled in this study; immune- histochemical analyses were
      performed on cancerous tissues and adjacent non- cancerous tissues of the
      patients. Serum Th17 cytokines of CRC patients and healthy controls were measured
      using a Luminex 200 analyzer. RESULTS: Cancerous tissues had more positive EV71
      antigen expression than adjacent non- cancerous tissues. In TNM II-III CRC, 59.9%
      of cancerous tissues were observed to be EV71 positive; on the contrary, 65.2% of
      the adjacent non- cancerous epithelium was EV71 negative. In TNM I CRC, all
      adjacent non- cancerous epithelium was virus negative, but in TNM IV, half of
      adjacent non- cancerous tissues were virus positive. Serum IL-10 were
      significantly higher in CRC patients than in healthy controls, and IL-10
      concentrations in the EV71 positive group were higher than those of the EV71
      negative group, with the highest IL-10 levels being observed in CRC patients with
      strong positive group (P < 0.05). Similar results were found for IL-21 and IL-23.
      IL-17 levels were higher in CRC patients than in healthy controls, there was no
      significant difference in IL-17 between the viral positive and viral negative
      groups (P > 0.05). CONCLUSION: Persistent existing EV71 viral antigens in
      intestinal tissues are positively associated with TNM III/IV CRC. EV71 latent
      infection recruits Th17 cells in the colorectal tumor site, stimulating Th17
      cytokine production that closely associated with CRC carcinogenesis.

PMID- 29175262
TI  - Gestational and Postnatal Cortisol Profiles of Women With Posttraumatic Stress
      Disorder and the Dissociative Subtype.
AB  - OBJECTIVE: To test the hypothesis that women with posttraumatic stress disorder
      (PTSD) have greater salivary cortisol levels across the diurnal curve and
      throughout gestation, birth, and the postpartum period than women who do not have
      PTSD. DESIGN: Prospective, longitudinal, biobehavioral cohort study. SETTING:
      Prenatal clinics at academic health centers in the Midwest region of the United
      States. PARTICIPANTS: Women expecting their first infants who fit with one of
      four cohorts: a nonexposed control group, a trauma-exposed control group, a group
      with PTSD, and a group with the dissociative subtype of PTSD. METHODS: In the
      first half of pregnancy, 395 women provided three salivary cortisol specimens on
      a single day for diurnal data. A subsample of 111 women provided three salivary
      cortisol specimens per day, 12 times, from early pregnancy to 6 weeks postpartum
      for longitudinal data. Trauma history, PTSD, and dissociative symptoms were
      measured via standardized telephone diagnostic interviews with the use of
      validated epidemiologic measures. Generalized estimating equations were used to
      determine group differences. RESULTS: Generalized estimating equations showed
      that women with the dissociative subtype of PTSD had the highest and flattest
      gestational cortisol level curves. The difference was greatest in early
      pregnancy, when participants in the dissociative subtype group had cortisol
      levels 8 times greater in the afternoon and 10 times greater at bedtime than
      those in the nonexposed control group. CONCLUSION: Women with the dissociative
      subtype of PTSD, a complex form associated with a history of childhood
      maltreatment, may have toxic levels of cortisol that contribute to
      intergenerational patterns of adverse health outcomes.

PMID- 29175263
TI  - Missing data and chance variation in public reporting of cancer stage at
      diagnosis: Cross-sectional analysis of population-based data in England.
AB  - BACKGROUND: The percentage of cancer patients diagnosed at an early stage is
      reported publicly for geographically-defined populations corresponding to
      healthcare commissioning organisations in England, and linked to pay-for
      performance targets. Given that stage is incompletely recorded, we investigated
      the extent to which this indicator reflects underlying organisational differences
      rather than differences in stage completeness and chance variation. METHODS: We
      used population-based data on patients diagnosed with one of ten cancer sites in
      2013 (bladder, breast, colorectal, endometrial, lung, ovarian, prostate, renal,
      NHL, and melanoma). We assessed the degree of bias in CCG (Clinical Commissioning
      Group) indicators introduced by missing-is-late and complete-case specifications
      compared with an imputed 'gold standard'. We estimated the Spearman-Brown
      (organisation-level) reliability of the complete-case specification. We assessed
      probable misclassification rates against current pay-for-performance targets.
      RESULTS: Under the missing-is-late approach, bias in estimated CCG percentage of
      tumours diagnosed at an early stage ranged from -2 to -30 percentage points,
      while bias under the complete-case approach ranged from -2 to +7 percentage
      points. Using an annual reporting period, indicators based on the least biased
      complete-case approach would have poor reliability, misclassifying 27/209 (13%)
      CCGs against a pay-for-performance target in current use; only half (53%) of CCGs
      apparently exceeding the target would be correctly classified in terms of their
      underlying performance. CONCLUSIONS: Current public reporting schemes for cancer
      stage at diagnosis in England should use a complete-case specification (i.e. the
      number of staged cases forming the denominator) and be based on three-year
      reporting periods. Early stage indicators for the studied geographies should not
      be used in pay-for-performance schemes.

PMID- 29175264
TI  - New methodologies to accurately assess circulating active transforming growth
      factor-beta1 levels: implications for evaluating heart failure and the impact of
      left ventricular assist devices.
AB  - Transforming growth factor-beta1 (TGF-beta1) has been used as a biomarker in
      disorders associated with pathologic fibrosis. However, plasma TGF-beta1
      assessment is confounded by the significant variation in reported normal values,
      likely reflecting variable release of the large pool of platelet TGF-beta1 after
      blood drawing. Moreover, current assays measure only total TGF-beta1, which is
      dominated by the latent form of TGF-beta1 rather than the biologically active
      form. To address these challenges, we developed methodologies to prevent ex vivo
      release of TGF-beta1 and to quantify active TGF-beta1. We then used these
      techniques to measure TGF-beta1 in healthy controls and patients with heart
      failure (HF) before and after insertion of left ventricular assist devices
      (LVAD). Total plasma TGF-beta1 was 1.0 +/- 0.60 ng/mL in controls and 3.76 +/-
      1.55 ng/mL in subjects with HF (P < 0.001), rising to 5.2 +/- 2.3 ng/mL following
      LVAD placement (P = 0.006). These results were paralleled by the active TGF-beta1
      values; controls had 3-16 pg/mL active TGF-beta1, whereas levels were 2.7-fold
      higher in patients with HF before, and 4.2-fold higher after, LVAD implantation.
      Total TGF-beta1 correlated with levels of the platelet-derived protein
      thrombospondin-1 (r = 0.87; P < 0.001), suggesting that plasma TGF-beta1 may
      serve as a surrogate indicator of in vivo platelet activation. von Willebrand
      factor high molecular weight multimers correlated inversely with TGF-beta1 levels
      (r = -0.63; P = 0.023), suggesting a role for shear forces in loss of these
      multimers and platelet activation. In conclusion, accurate assessment of
      circulating TGF-beta1 may provide a valuable biomarker for in vivo platelet
      activation and thrombotic disorders.

PMID- 29175265
TI  - Digital image analysis in breast pathology-from image processing techniques to
      artificial intelligence.
AB  - Breast cancer is the most common malignant disease in women worldwide. In recent
      decades, earlier diagnosis and better adjuvant therapy have substantially
      improved patient outcome. Diagnosis by histopathology has proven to be
      instrumental to guide breast cancer treatment, but new challenges have emerged as
      our increasing understanding of cancer over the years has revealed its complex
      nature. As patient demand for personalized breast cancer therapy grows, we face
      an urgent need for more precise biomarker assessment and more accurate
      histopathologic breast cancer diagnosis to make better therapy decisions. The
      digitization of pathology data has opened the door to faster, more reproducible,
      and more precise diagnoses through computerized image analysis. Software to
      assist diagnostic breast pathology through image processing techniques have been
      around for years. But recent breakthroughs in artificial intelligence (AI)
      promise to fundamentally change the way we detect and treat breast cancer in the
      near future. Machine learning, a subfield of AI that applies statistical methods
      to learn from data, has seen an explosion of interest in recent years because of
      its ability to recognize patterns in data with less need for human instruction.
      One technique in particular, known as deep learning, has produced groundbreaking
      results in many important problems including image classification and speech
      recognition. In this review, we will cover the use of AI and deep learning in
      diagnostic breast pathology, and other recent developments in digital image
      analysis.

PMID- 29175266
TI  - Tumor necrosis factor receptor-associated factor 6 as a nuclear factor kappa B
      modulating therapeutic target in cardiovascular diseases: at the heart of it all.
AB  - Inflammatory and immune signaling has been documented as a root cause of many
      cardiovascular pathologies. In this review, we explore the emerging role of tumor
      necrosis factor receptor-associated factor 6 (TRAF6)-nuclear factor kappa B (NF
      kappaB) signaling axis in atherosclerosis, ischemic heart disease, pathologic
      cardiac hypertrophy or heart failure, myocarditis, and sepsis-induced
      cardiomyopathy. We discuss the current understanding of cardiac inflammation in
      heart disease, present the TRAF6 signaling axis in the heart, then summarize what
      is known about TRAF6 in pathophysiology of heart disease including proof-of
      concept studies that identify the utility of blocking TRAF6 to attenuate cardiac
      dysfunction, which suggests that TRAF6 is a novel, druggable target in treating
      cardiovascular disease incurred by inflammatory processes.

PMID- 29175269
TI  - Sclerostin deficiency modifies the development of CKD-MBD in mice.
AB  - : Sclerostin is a soluble antagonist of canonical Wnt signaling and a strong
      inhibitor of bone formation. We present experimental data on the role of
      sclerostin in chronic kidney disease - bone mineral disorder (CKD-MBD). METHODS:
      We performed 5/6 nephrectomies in 36-week-old sclerostin-deficient (SOST-/-) B6
      mice and in C57BL/6J wildtype (WT) mice. Animals received a high phosphate diet
      for 11weeks. The bones were analyzed by high-resolution micro-computed tomography
      (MUCT) and quantitative bone histomorphometry. Aortic tissue was analyzed
      regarding the extent of vascular calcification. RESULTS: All nephrectomized mice
      had severe renal failure, and parathyroid hormone was highly increased compared
      to corresponding sham animals. All SOST-/- animals revealed the expected high
      bone mass phenotype. Overall, the bone compartment in WT and SOST-/- mice
      responded similarly to nephrectomy. In uremic WT animals, MUCT data at both the
      distal femur and lumbar spine revealed significantly increased trabecular volume
      compared to non-uremic WTs. In SOST-/- mice, the differences between trabecular
      bone volume were less pronounced when comparing uremic with sham animals.
      Cortical thickness and cortical bone density at the distal femur decreased
      significantly and comparably in both genotypes after 5/6 nephrectomy compared to
      sham animals (cortical bone density -18% and cortical thickness -32%). Overall,
      5/6 nephrectomy and concomitant hyperparathyroidism led to a genotype-independent
      loss of cortical bone volume and density. Overt vascular calcification was not
      detectable in either of the genotypes. CONCLUSION: Renal osteodystrophy changes
      were more pronounced in WT mice than in SOST-/- mice. The high bone mass
      phenotype of sclerostin deficiency was detectable also in the setting of chronic
      renal failure with severe secondary hyperparathyroidism.

PMID- 29175268
TI  - Peripheral vascular atherosclerosis in a novel PCSK9 gain-of-function mutant
      Ossabaw miniature pig model.
AB  - Hypercholesterolemia is a major risk factor for atherosclerosis. Remaining
      challenges in the management of atherosclerosis necessitate development of animal
      models that mimic human pathophysiology. We characterized a novel mutant pig
      model with DNA transposition of D374Y gain-of-function (GOF) cDNA of chimp
      proprotein convertase subtilisin/kexin type-9 (PCSK9), and tested the hypothesis
      that it would develop peripheral vascular remodeling and target organ injury in
      the kidney. Wild-type or PCSK9-GOF Ossabaw miniature pigs fed a standard or
      atherogenic diet (AD) (n = 7 each) were studied in vivo after 3 and 6 months of
      diet. Single-kidney hemodynamics and function were studied using multidetector
      computed tomography and kidney oxygenation by blood oxygen level-dependent
      magnetic resonance imaging. The renal artery was evaluated by intravascular
      ultrasound, aortic stiffness by multidetector computed tomography, and kidney
      stiffness by magnetic resonance elastography. Subsequent ex vivo studies included
      the renal artery endothelial function and morphology of abdominal aorta, renal,
      and femoral arteries by histology. Compared with wild type, PCSK9-GOF pigs had
      elevated cholesterol, triglyceride, and blood pressure levels at 3 and 6 months.
      Kidney stiffness increased in GOF groups, but aortic stiffness only in GOF-AD.
      Hypoxia, intrarenal fat deposition, oxidative stress, and fibrosis were observed
      in both GOF groups, whereas kidney function remained unchanged. Peripheral
      arteries in GOF groups showed medial thickening and development of atheromatous
      plaques. Renal endothelial function was impaired only in GOF-AD. Therefore, the
      PCSK9-GOF mutation induces rapid development of atherosclerosis in peripheral
      vessels of Ossabaw pigs, which is exacerbated by a high-cholesterol diet. This
      model may be useful for preclinical studies of atherosclerosis.

PMID- 29175270
TI  - Prevalence of pelvic Paget's disease of bone in France.

PMID- 29175267
TI  - The role of macrophage phenotype in regulating the response to radiation therapy.
AB  - Increasing experimental and clinical evidence has revealed a critical role for
      myeloid cells in the development and progression of cancer. The ability of
      monocytes and macrophages to regulate inflammation allows them to manipulate the
      tumor microenvironment to support the growth and development of malignant cells.
      Recent studies have shown that macrophages can exist in several functional states
      depending on the microenvironment they encounter in the tissue. These functional
      phenotypes influence not only the genesis and propagation of tumors, but also the
      efficacy of cancer therapies, particularly radiation. Early classification of the
      macrophage phenotypes, or "polarization states," identified 2 major states, M1
      and M2, that have cytotoxic and wound repair capacity, respectively. In the
      context of tumors, classically activated or M1 macrophages driven by interferon
      gamma support antitumor immunity while alternatively activated or M2 macrophages
      generated in part from interleukin-4 exposure hinder antitumor immunity by
      suppressing cytotoxic responses against a tumor. In this review, we discuss the
      role that the functional phenotype of a macrophage population plays in tumor
      development. We will then focus specifically on how macrophages and myeloid cells
      regulate the tumor response to radiation therapy.

PMID- 29175272
TI  - Fibrodysplasia ossificans progressiva in China.
AB  - Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare and devastating
      disorder characterized by cumulative episodes of progressive heterotopic
      ossification. It is estimated that there exist 600-700 patients in Mainland
      China. Nevertheless, due to the rarity, many FOP patients were initially
      misdiagnosed. Until now fewer than 150 patients have been identified in Mainland
      China. This review summarizes the epidemiology and clinical features of FOP
      patients, the progress of clinical and basic research in China, and the future of
      FOP care in China.

PMID- 29175271
TI  - Gnathodiaphyseal dysplasia: Severe atypical presentation with novel heterozygous
      mutation of the anoctamin gene (ANO5).
AB  - Gnathodiaphyseal dysplasia (GDD; OMIM #166260) is an ultra-rare autosomal
      dominant disorder caused by heterozygous mutation in the anoctamin 5 (ANO5) gene
      and features fibro-osseous lesions of the jawbones, bone fragility with recurrent
      fractures, and bowing/sclerosis of tubular bones. The physiologic role of ANO5 is
      unknown. We report a 5-year-old boy with a seemingly atypical and especially
      severe presentation of GDD and unique ANO5 mutation. Severe osteopenia was
      associated with prenatal femoral fractures, recurrent postnatal fractures, and
      progressive bilateral enlargement of his maxilla and mandible beginning at
      ~2months-of-age that interfered with feeding and speech and required four
      debulking operations. Histopathological analysis revealed benign fibro-osseous
      lesions resembling cemento-ossifying fibromas of the jaw without psammomatoid
      bodies. A novel, de novo, heterozygous, missense mutation was identified in exon
      15 of ANO5 (c.1553G>A; p.Gly518Glu). Our findings broaden the phenotypic and
      molecular spectra of GDD. Fractures early in life with progressive facial
      swelling are key features. We assessed his response to a total of 7 pamidronate
      infusions commencing at age 15months. Additional reports must further elucidate
      the phenotype, explore any genotype-phenotype correlation, and evaluate
      treatments.

PMID- 29175273
TI  - Nitrate removal from pharmaceutical wastewater using microbial electrochemical
      system supplied through low frequency-low voltage alternating electric current.
AB  - In this study, a microbial electrochemical system (MES) was designed to evaluate
      the effects of a low frequency-low voltage alternating electrical current on
      denitrification efficacy in the presence of ibuprofen as a low biodegradable
      organic carbon source. Cylindrical carbon cloth and stainless steel mesh
      electrodes containing a consortium of heterotrophic and autotrophic bacteria were
      mounted in the wall of the designed laboratory-scale bioreactor. The effects of
      inlet nitrate concentration (50-800mgL-1), retention time (2.5-24h), waveform
      magnitude (0.1-9.6Vp-p), adjustable direct current voltage added to offset
      voltage (0.1-4.9V), alternating current frequency (10-60Hz), and waveforms
      (sinusoidal, square, and ramp) were studied in this work. The results showed that
      the proposed system removes 800mgL-1 nitrate up to 95% during 6.5h. Optimum
      conditions were obtained in the 8Vp-p using a frequency of 10Hz of a sinusoidal
      waveform. The morphology studies confirmed bacterial morphology change when
      applying the alternating current. Dehydrogenase activity of biofilms formed on
      surface of stainless steel electrodes increased to 15.24MUgTFmgbiomasscm-2d. The
      maximum bacterial activity was obtained at a voltage of 8Vp-p. The experimental
      results revealed that the MES using a low frequency-low voltage alternating
      electrical current is a promising technique for nitrate removal from
      pharmaceutical wastewaters in the presence of low biodegradability of carbon
      sources such as ibuprofen.

PMID- 29175274
TI  - Provision of menstrual regulation with medication among pharmacies in three
      municipal districts of Bangladesh: a situation analysis.
AB  - OBJECTIVE: The objective was to assess the provision of the combination of
      mifepristone-misoprostol for menstrual regulation (MR) in randomly selected urban
      pharmacies in Bangladesh. STUDY DESIGN: We conducted a cross-sectional survey
      among 553 pharmacy workers followed by 548 mystery client visits to the same
      pharmacies in 3 municipal districts during July 2014-December 2015. RESULTS: The
      survey found that 99% of pharmacy workers visited had knowledge of MR procedures
      but only two-thirds (67%) could state the legal time limit correctly; they
      mentioned misoprostol (86%) over mifepristone-misoprostol combination (78%) as a
      procedure of MR with medication (MRM); 36% reported knowing the recommended
      dosage of mifepristone-misoprostol combination; 70% reported providing
      information on effectiveness of the medicines; 50% reported recommending at least
      one follow-up visit to them; 63% reported explaining possible complications of
      using the medications; and 47% reported offering any post-MR contraception to
      their clients. In contrast, mystery client visits found that the mifepristone
      misoprostol combination (69%) was suggested over misoprostol (51%) by the
      pharmacy workers; 54% provided the recommended dosage of mifepristone-misoprostol
      combination; 42% provided information on its effectiveness; 12% recommended at
      least one follow-up visit; 11% counseled on possible complications; and only 5%
      offered post-MR contraceptives to the mystery clients. CONCLUSIONS: We found
      knowledge gaps regarding recommended dosage for MRM and inconsistent practice in
      informing women on effectiveness, follow-up visits, possible complications and
      provision of post-MR contraceptives among the pharmacy workers, particularly
      during the mystery client visits. IMPLICATIONS: Pharmacy workers in Bangladesh
      need to be trained on legal time limits for MR services provision, on providing
      accurate information on disbursed medicine, and on proper referral mechanisms. A
      strong monitoring and regulatory system for pharmacy provision of MRM in
      pharmacies should be established.

PMID- 29175275
TI  - Understanding AVATAR therapy: who, or what, is changing?

PMID- 29175276
TI  - AVATAR therapy for auditory verbal hallucinations in people with psychosis: a
      single-blind, randomised controlled trial.
AB  - BACKGROUND: A quarter of people with psychotic conditions experience persistent
      auditory verbal hallucinations, despite treatment. AVATAR therapy (invented by
      Julian Leff in 2008) is a new approach in which people who hear voices have a
      dialogue with a digital representation (avatar) of their presumed persecutor,
      voiced by the therapist so that the avatar responds by becoming less hostile and
      concedes power over the course of therapy. We aimed to investigate the effect of
      AVATAR therapy on auditory verbal hallucinations, compared with a supportive
      counselling control condition. METHODS: We did this single-blind, randomised
      controlled trial at a single clinical location (South London and Maudsley NHS
      Trust). Participants were aged 18 to 65 years, had a clinical diagnosis of a
      schizophrenia spectrum (ICD10 F20-29) or affective disorder (F30-39 with
      psychotic symptoms), and had enduring auditory verbal hallucinations during the
      previous 12 months, despite continued treatment. Participants were randomly
      assigned (1:1) to receive AVATAR therapy or supportive counselling with
      randomised permuted blocks (block size randomly varying between two and six).
      Assessments were done at baseline, 12 weeks, and 24 weeks, by research assessors
      who were masked to therapy allocation. The primary outcome was reduction in
      auditory verbal hallucinations at 12 weeks, measured by total score on the
      Psychotic Symptoms Rating Scales Auditory Hallucinations (PSYRATS-AH). Analysis
      was by intention-to-treat with linear mixed models. The trial was prospectively
      registered with the ISRCTN registry, number 65314790. FINDINGS: Between Nov 1,
      2013, and Jan 28, 2016, 394 people were referred to the study, of whom 369 were
      assessed for eligibility. Of these people, 150 were eligible and were randomly
      assigned to receive either AVATAR therapy (n=75) or supportive counselling
      (n=75). 124 (83%) met the primary outcome. The reduction in PSYRATS-AH total
      score at 12 weeks was significantly greater for AVATAR therapy than for
      supportive counselling (mean difference -3.82 [SE 1.47], 95% CI -6.70 to -0.94;
      p<0.0093). There was no evidence of any adverse events attributable to either
      therapy. INTERPRETATION: To our knowledge, this is the first powered, randomised
      controlled trial of AVATAR therapy. This brief, targeted therapy was more
      effective after 12 weeks of treatment than was supportive counselling in reducing
      the severity of persistent auditory verbal hallucinations, with a large effect
      size. Future multi-centre studies are needed to establish the effectiveness of
      AVATAR therapy and, if proven effective, we think it should become an option in
      the psychological treatment of auditory verbal hallucinations. FUNDING: Wellcome
      Trust.

PMID- 29175277
TI  - The association between child exposure to intimate partner violence (IPV) and
      perpetration of IPV in adulthood-A systematic review.
AB  - Increasingly recognized as a distinct form of childhood maltreatment, children's
      exposure to intimate partner violence (IPV) has been shown to be associated with
      an array of negative psychosocial outcomes, including elevated risk for
      additional violence over the life course. Although studies have identified child
      exposure to IPV as a predictor of IPV perpetration in adulthood, no review has
      critically evaluated the methodology of this quantitative work. The present study
      examines the association between childhood exposure to IPV and the perpetration
      of IPV in adulthood based on a systematic review of the literature from inception
      to January 4, 2016. Databases searched included Medline, Embase, PsycINFO,
      CINAHL, Cochrane Database of Systematic Reviews, Sociological Abstracts and ERIC.
      Database searches were complemented with backward and forward citation chaining.
      Studies were critically appraised using the Quality Assessment Tool for
      Observational Cohort and Cross-Sectional Studies. Of 5601 articles identified by
      the search, 19 studies were included for data extraction. Sixteen of these
      studies found that child exposure to IPV was significantly and positively
      associated with adult IPV perpetration; three studies reported null findings. The
      methodological quality of the studies was low. Work thus far has tended to focus
      on child exposure to physical IPV and the perpetration of physical IPV within
      heterosexual contexts. In addition, measures of child exposure to IPV vary in
      their classification of what exposure entails. We critically discuss the
      strengths and limitations of the existing evidence and the theoretical frameworks
      informing this work.

PMID- 29175278
TI  - Animal cruelty as an indicator of family trauma: Using adverse childhood
      experiences to look beyond child abuse and domestic violence.
AB  - Youth who engage in animal cruelty are known to be at increased risk of
      perpetrating violence on other people in their lives including peers, loved ones,
      and elder family members. These youths have often been exposed to family
      violence, including animal cruelty perpetrated on their beloved pets by violent
      adults. The current study utilizes a data set of 81,000 juvenile offenders whose
      adverse childhood experiences are known and includes 466 youth who self-report
      engaging in animal cruelty. Compared to the larger group of juvenile offenders,
      the children admitting to engaging in animal cruelty are younger at time of first
      arrest, more likely to be male, and more likely to be White. When looking at
      their reports of adverse childhood experiences (ACEs), they are more likely than
      other juvenile offenders to have an array of adverse experiences beyond family
      violence and to have four or more ACEs. Although the youth who are cruel to
      animals are already troubled, the fact that they present to law enforcement at
      early ages provides early opportunities for intervention. Service providers
      outside the law enforcement field, such as teachers, physicians, veterinarians
      and animal control officers may be able to identify these vulnerable youth, and
      refer them to needed services before violence is visited on other humans.

PMID- 29175279
TI  - Genetic screening in two Iranian families with early-onset Alzheimer's disease
      identified a novel PSEN1 mutation.
AB  - A subset of early-onset Alzheimer's disease is inherited as an autosomal-dominant
      trait and is associated with mutations in the genes encoding beta-amyloid
      precursor protein, presenilin 1, or presenilin 2. In this study, we identified 2
      PSEN1 mutations (1 novel and 1 known) in 2 unrelated Iranian families with
      autosomal-dominant Alzheimer's disease. The disease progressed rapidly with a
      mean age at onset of 33 and 42 years and an age at death ranging from 43 to 48
      years.

PMID- 29175280
TI  - Surfing as a risk factor for sensitization to poly(gamma-glutamic acid) in
      fermented soybeans, natto, allergy.
AB  - BACKGROUND: Poly(gamma-glutamic acid) (PGA) is an allergen in natto, fermented
      soybeans, which causes late-onset anaphylaxis. We hypothesized that jellyfish
      stings sensitize adults to PGA because a surfer had allergies to both natto and
      jellyfish, whose sting contains PGA. The aim of the study was to identify
      behavioral factors, such as marine sports, associated with PGA sensitization.
      METHODS: Outpatients diagnosed with food allergies based on relevant clinical
      history, positive skin test and/or food challenge test answered a questionnaire
      during a regular visit in 2016. RESULTS: Questionnaire data from 140 outpatients
      were analyzed. These patients were divided into two groups: natto allergy group
      (13 patients, M:F = 10:3, mean age 40.6 years) and non-natto allergy group (127
      patients, M:F = 46:81, mean age 44.5 years). All patients with natto allergy had
      positive results in skin prick test and basophil activation test with PGA. Of
      these, 92.3% had a marine sport hobby, especially surfing (84.6%). PGA
      sensitization was independently associated with marine sports (odds ratio, 278.0,
      95 percent confidence interval, 36.9-6315.9, p < 0.001) adjusted for male sex and
      sea bathing, but not with male sex or sea bathing. In addition, although there
      was no significant difference in the experience of marine sports between natto
      and non-natto allergy groups, the natto allergy group participated significantly
      more frequently in marine sports than the non-natto allergy group (p < 0.001).
      There was no significant difference between natto consumption amount and PGA
      sensitization. CONCLUSIONS: Surfing is a risk factor for PGA sensitization in
      those with allergy to natto.

PMID- 29175281
TI  - Predicting Survival in Patients With Heart Failure With an Implantable
      Cardioverter Defibrillator: The Heart Failure Meta-Score.
AB  - BACKGROUND: Prognostic evaluation in heart failure (HF) is important to predict
      future events and decide timely management. Many HF patients are treated with the
      use of an implantable cardioverter-defibrillator (ICD). This study aimed to
      validate a meta-analytically derived prognostic score to predict survival in ICD
      HF patients. METHODS AND RESULTS: The HF Meta-score includes 14 independent
      mortality predictors identified in a meta-analysis, including age, sex,
      ethnicity, diabetes, chronic obstructive pulmonary disease, peripheral vascular
      disease, atrial fibrillation, ischemic cardiomyopathy, history of HF admission,
      New York Heart Association functional class, left ventricular ejection fraction,
      renal function, QRS duration, secondary prevention indication, and ICD shocks.
      The HF Meta-score performance was evaluated in comparison with the Seattle Heart
      Failure Model (SHFM) and the SHOCKED predictors in a cohort of 9860 ambulatory
      ICD patients from the Ontario provincial database for 2007-2011. During 3-year
      follow-up, 1816 patients died. The HF Meta-score showed excellent calibration,
      very good discrimination (c-statistic 0.74) and enhanced risk classification
      compared with the SHOCKED predictors, with better reclassifying in 19% and 56% of
      patients for 1- and 3-year survival, respectively. HF Meta-score performance was
      similar to the SHFM. CONCLUSIONS: The HF Meta-score is an evidence-based derived
      model that provides an accurate prognosis assessment in HF patients with ICDs.
      Its development strategy permits further incorporation of new predictors when
      evidence becomes available.

PMID- 29175282
TI  - Comment on: gastric mesenchymal tumors as incidental findings during Roux-en-Y
      gastric bypass.

PMID- 29175283
TI  - Influence of continuous positive airway pressure on postoperative leakage in
      bariatric surgery.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) affects two third of morbidly obese
      individuals undergoing bariatric surgery. Perioperative usage of continuous
      positive airway pressure (CPAP) is advised for moderately and severe OSA to avoid
      respiratory failure and cardiac events. CPAP increases the air pressure in the
      upper airway, but also may elevate the air pressure in the esophagus and stomach.
      Concern exists that this predisposes to mechanical stress resulting in suture or
      staple line disruption (further referred to as suture line disruption).
      OBJECTIVES: To evaluate whether perioperative CPAP usage is associated with an
      increased risk of suture line disruption after bariatric surgery. SETTING:
      Obesity Center Amsterdam, OLVG-west, Amsterdam, the Netherlands. METHODS: All
      patients who underwent bariatric surgery including a suture line were eligible
      for inclusion. Only patients with information regarding OSA severity as defined
      by the apnea-hypopnea-index and postoperative CPAP usage were included. RESULTS:
      From November 2007 to August 2016, postoperative CPAP status was documented in
      2135 patients: 497 (23.3%) used CPAP postoperatively, whereas 1638 (76.7%) used
      no CPAP. Mean body mass index was 44.1 kg/m2 (standard deviation 6.6). Suture
      line disruption occurred in 25 patients (1.2%). The leakage rate was not
      associated with CPAP usage (8 [1.6%] in CPAP group versus 17 [1%] in non-CPAP
      group, P = .300). CPAP was no risk factor for suture line disruption in
      multivariable analysis as well. CONCLUSION: Postoperative CPAP does not appear to
      increase the risk of suture line disruption in bariatric surgery. CPAP is
      recommended in all patients with moderate or severe OSA who undergo bariatric
      surgery.

PMID- 29175284
TI  - Increased Risk of Vitiligo Following Anti-Tumor Necrosis Factor Therapy: A 10
      Year Population-Based Cohort Study.
AB  - Anti-tumor necrosis factor-alpha (anti-TNF) therapy is used to treat a wide range
      of chronic inflammatory conditions. However, there has been an increasing number
      of reports of development of vitiligo and alopecia areata secondary to anti-TNF
      therapy. In this study, we investigated the risks of vitiligo and alopecia areata
      in patients with ankylosing spondylitis, Crohn's disease, or ulcerative colitis,
      who were treated with or without anti-TNF therapy using data from the Korean
      National Health Insurance Claims database from 2007 to 2016. The study comprised
      11,442 patients treated with anti-TNF agents (anti-TNF group), and an equal
      number of age-, sex-, and disease- matched patients treated without anti-TNF
      agents (unexposed group). Multivariable Cox proportional hazards models were used
      to compare the risks of vitiligo and alopecia areata between the two groups. A
      significantly increased risk of vitiligo (hazard ratio = 1.99, 95% confidence
      interval = 1.06-3.75) was observed in the anti-TNF group compared to the
      unexposed group (5.9/10,000 person-years vs. 2.5/10,000 person-years). In
      subgroup analyses, younger patients and those treated with etanercept showed
      higher risks of vitiligo. The risk of alopecia areata was not significantly
      different between the two groups. Our results provide insight on the role of
      cytokine imbalance in the pathogenesis of vitiligo.

PMID- 29175285
TI  - Development of HyBeacon(r) probes for specific mRNA detection using body fluids
      as a model system.
AB  - HyBeacons are linear oligonucleotides which incorporate fluorescent dyes
      covalently linked to internal nucleotides. They have previously been used with
      PCR and isothermal amplification to interrogate SNPs and STRs in fields as
      diverse as clinical diagnostics, food authentication, and forensic DNA profiling.
      This work explores their use for the identification of expressed gene sequences
      through mRNA profiling. The use of mRNA is becoming increasingly common in
      forensic casework to identify body fluids on evidence items, as it offers higher
      specificity and fewer false positives than current chemical presumptive testing
      methods. The work presented here details the development of a single-step one
      tube RT-PCR assay to detect the presence of body fluids of forensic interest
      (saliva, blood, seminal fluid, vaginal fluid and menstrual blood) using
      HyBeacon(r) probes and melt curve analysis. Each assay shows a high degree of
      specificity to the target body fluid mRNA suggesting there is no requirement to
      remove genomic DNA prior to analysis. Of the five assays developed, four were
      able to detect between 10 and 100 copies of target cDNA, the fifth 1000 copies of
      target. The results presented here demonstrate that such an approach can be
      optimised for non-expert users and further areas of work are discussed.

PMID- 29175286
TI  - MicroRNA-34a modulates the Notch signaling pathway in mice with congenital heart
      disease and its role in heart development.
AB  - The objective of the study was to elucidate the mechanism by which microRNA-34a
      (miR-34a) influences heart development and participates in the pathogenesis of
      congenital heart disease (CHD) by targeting NOTCH-1 through the Notch signaling
      pathway. Forty D7 pregnant mice were recruited for the purposes of the study and
      served as the CHD (n=20, successfully established as CHD model) and normal (n=20)
      groups. The positive expression of the NOTCH-1 protein was evaluated by means of
      immunohistochemistry. Embryonic endocardial cells (ECCs) were assigned into the
      normal, blank, negative control (NC), miR-34a mimics, miR-34a inhibitors, miR-34a
      inhibitors+siRNA-NOTCH-1, siRNA-NOTCH-1, miR-34a mimics+NOTCH-1 OE and miR-34a
      mimics+crispr/cas9 (mutant NOTCH-1) groups. The expressions of miR-34a, NOTCH-1,
      Jagged1, Hes1, Hey2 and Csx in cardiac tissues and ECCs were determined by both
      RT-qPCR and western blotting methods. MTT assay and flow cytometry were conducted
      for cell proliferation and apoptosis measurement. A dual luciferase reporter
      assay was applied to demonstrate that NOTCH-1 was the target gene of miR-34a. In
      comparison to the normal group, the expressions of miR-34a, Jagged1, Hes1 and
      Hey2 displayed up-regulated levels, while the expressions of NOTCH-1 and Csx were
      down-regulated in the CHD group. Compared with the blank and NC groups, the miR
      34a mimics and siRNA-NOTCH-1 groups displayed reduced expressions of NOTCH-1 and
      Csx as well as a decreased proliferation rate, higher miR-34a, Jagged1, Hes1 and
      Hey2 expressions and an increased rate of apoptosis; while an reverse trend was
      observed in the miR-34a inhibitors group. The expressions of MiR-34a recorded
      increased levels in the miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9
      (mutant NOTCH-1) groups, however no changes in the expressions of NOTCH-1,
      Jagged1, Hes1, Hey2, Csx, as well as cell proliferation and apoptosis were
      observed when compared to the blank and NC groups. The results of our study
      demonstrated that miR-34a increases the risk of CHD through its downregulation of
      NOTCH-1 by modulating the Notch signaling pathway.

PMID- 29175287
TI  - Energy drinks and adolescents - A hepatic health hazard?

PMID- 29175288
TI  - MRCZ - A file format for cryo-TEM data with fast compression.
AB  - The introduction of fast CMOS detectors is moving the field of transmission
      electron microscopy into the computer science field of big data. Automated data
      pipelines control the instrument and initial processing steps which imposes more
      onerous data transfer and archiving requirements. Here we conduct a technical
      demonstration whereby storage and read/write times are improved 10* at a dose
      rate of 1 e-/pix/frame for data from a Gatan K2 direct-detection device by
      combination of integer decimation and lossless compression. The example project
      is hosted at github.com/em-MRCZ and released under the BSD license.

PMID- 29175289
TI  - Mapping of recent brachiopod microstructure: A tool for environmental studies.
AB  - Shells of brachiopods are excellent archives for environmental reconstructions in
      the recent and distant past as their microstructure and geochemistry respond to
      climate and environmental forcings. We studied the morphology and size of the
      basic structural unit, the secondary layer fibre, of the shells of several extant
      brachiopod taxa to derive a model correlating microstructural patterns to
      environmental conditions. Twenty-one adult specimens of six recent brachiopod
      species adapted to different environmental conditions, from Antarctica, to New
      Zealand, to the Mediterranean Sea, were chosen for microstructural analysis using
      SEM, TEM and EBSD. We conclude that: 1) there is no significant difference in the
      shape and size of the fibres between ventral and dorsal valves, 2) there is an
      ontogenetic trend in the shape and size of the fibres, as they become larger,
      wider, and flatter with increasing age. This indicates that the fibrous layer
      produced in the later stages of growth, which is recommended by the literature to
      be the best material for geochemical analyses, has a different morphostructure
      and probably a lower organic content than that produced earlier in life. In two
      species of the same genus living in seawater with different temperature and
      carbonate saturation state, a relationship emerged between the microstructure and
      environmental conditions. Fibres of the polar Liothyrella uva tend to be smaller,
      rounder and less convex than those of the temperate Liothyrella neozelanica,
      suggesting a relationship between microstructural size, shell organic matter
      content, ambient seawater temperature and calcite saturation state.

PMID- 29175290
TI  - Trends and key correlates of prescription opioid injection misuse in the United
      States.
AB  - BACKGROUND: Despite concerns over increasing harms associated with prescription
      opioid injection misuse, there is a paucity of research on the magnitude,
      characteristics, injection practices, and syringe sources for people who inject
      prescription opioids; limiting the implementation of targeted policy and
      programmatic initiatives. MATERIALS AND METHODS: Data from the 2003 through 2014
      National Surveys on Drug Use and Health were used to estimate prescription opioid
      injection trends and examine risky injection practices and syringe sources for
      people who inject prescription opioids. Multivariable logistic regression was
      used to identify characteristics associated with prescription opioid injection.
      RESULTS: Among people 12years or older, the rate of prescription opioid injection
      misuse increased from 1.6 per 1000 in 2003-2005 to 2.7 per 1000 in 2012-2014 (p
      value for trend <0.05). Groups with increased odds of prescription opioid
      injection included: males, non-Hispanic whites, having an annual household income
      <$50,000, the uninsured, people with Medicaid, and people with past-year use
      disorders for cocaine, heroin, or prescription opioids. Risky injection practices
      such as reusing a needle and sharing needles were common among people with a
      history of prescription opioid injection misuse. CONCLUSION: This study found
      significant increases in prescription opioid injection misuse trends in the U.S.
      These findings underscore the need to bring to scale evidence-based interventions
      to increase the provision of medication-assisted treatment for opioid use
      disorders and expand access to comprehensive risk-reduction services for people
      who inject drugs.

PMID- 29175291
TI  - Testing competing models of injunctive and descriptive norms for proximal and
      distal reference groups on alcohol attitudes and behavior.
AB  - INTRODUCTION: Injunctive norms represent perceptions regarding the extent that
      others approve of a behavior, whereas descriptive norms represent perceptions of
      the extent that others engage in a behavior. This study evaluated competing path
      models, varying in the representation of injunctive and descriptive norm
      constructs, to forecast alcohol attitudes and use. METHODS: College students
      (N=326) answered questions about their normative perceptions regarding three
      relevant reference groups (typical students, friends, and parents) in the form of
      alcohol injunctive and descriptive norms. Personal alcohol attitudes (approval)
      and usage were assessed one month later. RESULTS: The path analysis model
      arranged by injunctive versus descriptive found that injunctive norms explained
      attitudes, but descriptive norms contributed to behavior. In the path analysis
      model of constructs organized by reference groups, friend and parent norms
      uniquely contributed to attitudes, but typical student, friend, and parental
      norms contributed to use. Finally, the comprehensive model based on each
      reference group combination with injunctive and descriptive norms (e.g., typical
      student injunctive) determined that friend injunctive norms and parent injunctive
      norms uniquely forecasted alcohol attitudes, whereas typical student injunctive
      norms, typical student descriptive norms, and friend descriptive norms forecasted
      behavior. CONCLUSIONS: A novel contribution of the study is the scrutiny of
      competing models of alcohol norms using the same multifaceted measures. Disparate
      implications emerge about the role of subjective norms as a function of the
      approach to compute the constructs. The most nuanced insights were obtained in
      the final comprehensive model involving the representation of norms at the finest
      level of specificity.

PMID- 29175292
TI  - Thinking while drinking: Fear of negative evaluation predicts drinking behaviors
      of students with social anxiety.
AB  - College students with social anxiety disorder experience more alcohol-related
      negative consequences, regardless of the amount of alcohol they consume. Social
      anxiety refers to psychological distress and physiological arousal in social
      situations due to an excessive fear of negative evaluation by others. The current
      study examined within-group differences in alcohol-related negative consequences
      of students who met or exceeded clinically-indicated social anxiety symptoms. In
      particular, we tested a sequential mediation model of the cognitive (i.e., fear
      of negative evaluation) and behavioral (protective behavioral strategies)
      mechanisms for the link between social anxiety disorder subtypes (i.e.,
      interaction and performance-type) and alcohol-related negative consequences.
      Participants were 412 traditional-age college student drinkers who met or
      exceeded the clinically-indicated threshold for social anxiety disorder and
      completed measures of fear of negative evaluation, protective behavioral
      strategies (controlled consumption and serious harm reduction), and alcohol
      related negative consequences. Fear of negative evaluation and serious harm
      reduction strategies sequentially accounted for the relationship between
      interaction social anxiety disorder and alcohol-related negative consequences,
      such that students with more severe interaction social anxiety symptoms reported
      more fear of negative evaluation, which was related to more serious harm
      reduction strategies, which predicted fewer alcohol-related negative
      consequences. Future directions and implications are discussed.

PMID- 29175293
TI  - Depression symptoms and reasons for gambling sequentially mediate the
      associations between insecure attachment styles and problem gambling.
AB  - One of the central pathways to problem gambling (PG) is gambling to cope with
      negative moods, which is a cardinal feature of depression. Insecure attachment
      styles are also etiologically related to depression; and, therefore, by
      extension, those who are insecurely attached may engage in excessive gambling
      behaviors to cope with depression. In this study, we aimed to evaluate this and
      to this end predicted that depression severity and coping motives for gambling
      would conjointly mediate the relations between insecure attachment styles and PG.
      Data came from a larger investigation of PG within mood disorders. Participants
      exhibited a lifetime depressive or bipolar disorder and endorsed a mood episode
      within the past ten years. Participants (N=275) completed self-report measures
      during a two-day assessment. Path analysis supported two main indirect effects.
      First, anxious attachment predicted elevated depression, which in turn predicted
      increased coping motives for gambling, which subsequently predicted greater PG
      severity. Second, this double mediational pathway was also observed for avoidant
      attachment. Results suggest that insecure attachment relates to PG via depressive
      symptoms and coping-related gambling motives. Mood symptoms and associated
      gambling motives are malleable and are promising targets of gambling
      interventions for insecurely attached individuals.

PMID- 29175294
TI  - Parachuting psychoactive substances: Pharmacokinetic clues for harm reduction.
AB  - BACKGROUND: Parachuting, also called bombing, is a way to ingest psychoactive
      substances wrapped into cigarette paper, toilet paper, etc. There is little data
      describing parachuting in terms of substances use, context of use and, most
      importantly, the motivations for using such wrappers, although some authors
      hypothesized that parachute could be used for pharmacokinetic reason. However,
      inconsistently, some authors report that parachutes are used for sustained
      release whereas others report that users are looking for an immediate effect.
      RESEARCH DESIGN AND METHODS: Considering parachute as a "home-made" dosage form,
      we have applied the dissolution testing to characterize the dissolution
      performance of a substance wrapped into a parachute and to characterize whether a
      parachute represents an immediate-release form or not. RESULTS: This in-vitro
      study provides the first pharmacokinetic data for drugs wrapped in parachutes. It
      shows that parachute acts as sustained-release form when made with a cigarette
      paper wrapper, but as immediate release form in the presence of alcohol or if
      wrapped with toilet paper. CONCLUSIONS: An important message to harm reduction is
      that users must be aware that a parachute can have unexpected pharmacokinetics
      and have to avoid taking another parachute in the absence of an immediate-effect
      to avoid overdose.

PMID- 29175295
TI  - Pain anxiety differentially mediates the association of pain intensity with
      function depending on level of intolerance of uncertainty.
AB  - Uncertainty about symptom duration, cause, prognosis and treatment is common in
      patients who seek medical care, yet individual ability to manage this uncertainty
      varies. Intolerance of uncertainty is considered an important factor in the
      etiology and persistence of negative emotions- in particular, depression and
      anxiety. We explored the contribution of intolerance of uncertainty to anxiety
      due to pain and physical function in patients seeking care at an orthopedic
      medical practice. Participants (N = 105, mean age of 51 +/- 17, 63% male) were
      administered PROMIS Physical Function v1.2 Upper Extremity CAT, Numerical Rating
      Scale (NRS), Pain Anxiety Symptoms Scale-short form (PASS-20), and the
      Intolerance of Uncertainty Scale-short version (IUS-12). Results showed that the
      mediating role of pain anxiety is contingent upon the level of intolerance of
      uncertainty. Specifically, a minimum level of intolerance of uncertainty is
      required for the development of pain anxiety and its effect on function, and as
      intolerance of uncertainty rises from low to medium to high levels, the effect of
      pain on function goes from being independent of the anxiety to being more and
      more carried by and through anxiety about pain. These findings support the
      contention that intolerance of uncertainty plays a crucial role in the
      relationship between pain, pain anxiety, and physical function. Intolerance of
      uncertainty appears to be a trans-diagnostic target for coping skills training.

PMID- 29175296
TI  - Eating styles in major depressive disorder: Results from a large-scale study.
AB  - Depressed persons have been found to present disturbances in eating styles, but
      it is unclear whether eating styles are different in subgroups of depressed
      patients. We studied the association between depressive disorder, severity,
      course and specific depressive symptom profiles and unhealthy eating styles.
      Cross-sectional and course data from 1060 remitted depressed patients, 309
      currently depressed patients and 381 healthy controls from the Netherlands Study
      of Depression and Anxiety were used. Depressive disorders (DSM-IV based
      psychiatric interview) and self-reported depressive symptoms (Inventory of
      Depressive Symptomatology) were related to emotional, external and restrained
      eating (Dutch Eating Behavior Questionnaire) using analyses of covariance and
      linear regression. Remitted and current depressive disorders were significantly
      associated with higher emotional eating (Cohen's d = 0.40 and 0.60 respectively,
      p < 0.001) and higher external eating (Cohen's d = 0.20, p = 0.001 and Cohen's d
      = 0.32, p < 0.001 respectively). Little differences in eating styles between
      depression course groups were observed. Associations followed a dose-response
      association, with more emotional and external eating when depression was more
      severe (both p-values <0.001). Longer symptom duration was also associated to
      more emotional and external eating (p < 0.001 and p = 0.001 respectively). When
      examining individual depressive symptoms, neuro-vegetative depressive symptoms
      contributed relatively more to emotional and external eating, while mood and
      anxious symptoms contributed relatively less to emotional and external eating. No
      depression associations were found with restrained eating. Intervention programs
      for depression should examine whether treating disordered eating specifically in
      those with neuro-vegetative, atypical depressive symptoms may help prevent or
      minimize adverse health consequences.

PMID- 29175297
TI  - Impulsivity in unaffected adolescent biological relatives of schizophrenia
      patients.
AB  - OBJECTIVE: Although schizophrenia is not a prototypic impulse-control disorder,
      patients report more impulsive behaviors, have higher rates of substance use, and
      show dysfunction in brain circuits that underlie impulsivity. We investigate
      impulsivity in unaffected biological relatives of schizophrenia patients to
      further understand the relationships between schizophrenia risk and impulse
      control during adolescence. METHOD: Group differences in impulsivity (UPPS-P
      Impulsive Behavior Scale and delay discounting) were tested in 210 adolescents
      contrasting 39 first- and 53 second-degree biological relatives of schizophrenia
      patients, and 118 subjects with no schizophrenia family history (NSFH). RESULTS:
      Compared to NSFH adolescents and to second-degree relatives, first-degree
      relatives of schizophrenia patients had increased impulsivity-related behaviors
      (higher UPPS-P Perseverance, Positive Urgency and Premeditation subscale scores)
      and greater preference for immediate rewards (smaller AUC and larger discounting
      constant). Second-degree relatives did not differ significantly from NSFH
      adolescents on self-report impulsive behaviors or on measures of impulsive
      decision-making. These group differences remained even after careful
      consideration of potential confounding factors. CONCLUSION: Impulsivity is
      associated with schizophrenia risk, and its severity increases with greater
      familial relatedness to the schizophrenia proband. Additional studies are needed
      to understand the role impulsivity may play in mediating schizophrenia
      susceptibility during adolescence.

PMID- 29175298
TI  - Does type 2 diabetes affect the on-treatment levels of direct oral anticoagulants
      in patients with atrial fibrillation?
AB  - AIMS: Type 2 diabetes (T2D) is connected with several abnormalities in
      haemostasis; and with higher risk of stroke and systemic embolism in patients
      with non-valvular atrial fibrillation (NV-AF). However, it is recently unknown
      whether T2D affects the activity of direct oral anticoagulants (DOACs). The aim
      of this study was to determine the impact of T2D on DOACs activity in patients
      with NV-AF. METHODS: This pilot prospective study enrolled totally 65 patients
      with NV-AF (20 dabigatran-treated, 110 mg/twice daily; 28 rivaroxaban-treated, 15
      mg/daily; 17 apixaban-treated, 5 mg/twice daily). 25 patients had T2D (8
      dabigatran-treated, 11 rivaroxaban-treated, and 6 apixaban-treated). DOAC
      activity was tested with Hemoclot(r) Thrombin Inhibitor assay in dabigatran
      treated patients, and with factor Xa-calibrated anti-Xa chromogenic analysis in
      rivaroxaban- and apixaban-treated patients prior and two hours after drug
      administration. RESULTS: There were no significant differences in dabigatran
      baseline (62.1 +/- 8.0 vs. 51.8 +/- 38.9 ng/ml, p = .76) and 2-h-post-drug
      administration (91.7 +/- 57.2 vs. 72.2 +/- 33.2 ng/ml, p = .48) activity
      comparing T2D and non-diabetic patients. Similarly, no significant differences
      were found in rivaroxaban baseline (35.9 +/- 22.5 vs. 55.3 +/- 45.1 ng/ml, p =
      .19) and 2-h-post-drug-administration (145.7 +/- 74.1 vs. 202.6 +/- 135.0 ng/ml,
      p = .22) anti-Xa activity. In addition, no significant differences were present
      in apixaban baseline (96.0 +/- 54.5 vs. 63.9 +/- 36.8 ng/ml, p = .24) and 2-h
      post-drug-administration (151.0 +/- 78.3 vs. 151.7 +/- 59.1 ng/ml, p = .98) anti
      Xa activity between T2D and non-diabetic patients. CONCLUSIONS: This pilot study
      did not detect differences in DOACs activity according to T2D status in patients
      with NV-AF.

PMID- 29175299
TI  - Verbal labels facilitate tactile perception.
AB  - One of the key statements of linguistic relativity is that language has a causal
      effect on perception. Although much previous research has addressed such putative
      language perception causality, no firm proof is available thus far which
      demonstrates that verbal labels help or otherwise influence perceptual processes.
      Here, we tested the hypothesis of language perception causality by using novel,
      minimally-different tactile-patterned stimuli applied to the finger, which
      initially could not be discriminated by our participants. By combining novel
      verbal pseudoword- and novel tactile-patterned stimuli in an implicit learning
      experiment, we show a language-induced facilitation in tactile-patterned stimulus
      discrimination. After one week of intensive yet implicit learning of tactile
      stimuli in the presence of irrelevant consistent verbal labels, participants
      demonstrated significant discrimination improvement. In contrast, the same
      participants showed no improvement in discriminating tactile-patterned stimuli
      that had been learnt in the context of variable linguistic stimuli. These results
      show that specific mental links between verbal labels and perceptual information
      brought about by their correlated presentation enable one to better discriminate
      said sensory information (and build percepts).

PMID- 29175300
TI  - Perfluorooctanoic acid and low birth weight: Estimates of US attributable burden
      and economic costs from 2003 through 2014.
AB  - BACKGROUND AND OBJECTIVE: In utero exposure to perfluorooctanoic acid (PFOA) has
      been associated with decreases in birth weight. We aimed to estimate the
      proportion of PFOA-attributable low birth weight (LBW) births and associated
      costs in the US from 2003 to 2014, a period during which there were industry
      initiated and regulatory activities aimed at reducing exposure. METHODS: Serum
      PFOA levels among women 18-49 years were obtained from the National Health and
      Nutrition Examination Survey (NHANES) for 2003-2014; birth weight distributions
      were obtained from the Vital Statistics Natality Birth Data. The exposure
      response relationship identified in a previous meta-analysis (18.9g decrease in
      birth weight per 1ng/mL of PFOA) was applied to quantify PFOA-attributable LBW
      (reference level of 3.1ng/mL for our base case, 1 and 3.9ng/mL for sensitivity
      analyses). Hospitalization costs and lost economic productivity were also
      estimated. RESULTS: Serum PFOA levels remained approximately constant from 2003
      2004 (median: 3.3ng/mL) to 2007-2008 (3.5ng/mL), and declined from 2009-2010
      (2.8ng/mL) to 2013-2014 (1.6ng/mL). In 2003-2004, an estimated 12,764 LBW cases
      (4% of total for those years) were potentially preventable if PFOA exposure were
      reduced to the base case reference level (10,203 cases in 2009-2010 and 1,491 in
      2013-2014). The total cost of PFOA-attributable LBW for 2003 through 2014 was
      estimated at $13.7 billion, with $2.97 billion in 2003-2004, $2.4 billion in 2009
      2010 and $347 million in 2013-2014. CONCLUSIONS: Serum PFOA levels began to
      decline in women of childbearing age in 2009-2010. Declines were of a magnitude
      expected to meaningfully reduce the estimated incidence of PFOA-attributable LBW
      and associated costs.

PMID- 29175301
TI  - A straightforward assay to evaluate DNA integrity and optimize next-generation
      sequencing for clinical diagnosis in oncology.
AB  - Next generation sequencing (NGS) has become an informative tool to guide cancer
      treatment and conduce a personalized approach in oncology. The biopsy collected
      for pathologic analysis is usually stored as formalin-fixed paraffin-embedded
      (FFPE) blocks and then availed for molecular diagnostic, resulting in DNA
      molecules that are invariably fragmented and chemically modified. In an attempt
      to improve NGS based diagnostics in oncology we developed a straightforward DNA
      integrity assessment assay based on qPCR, defining clear parameters to whether
      NGS sequencing results is accurate or when it should be analyzed with caution. We
      performed DNA extraction from 12 tumor samples from diverse tissues and accessed
      DNA integrity by straightforward qPCR assays. In order to perform a cancer panel
      NGS sequencing, DNA library preparation was performed using RNA capture baits.
      Reads were aligned to the reference human genome and mutation calls were further
      validated by Sanger sequencing. Results obtained by the DNA integrity assays
      correlated to the efficiency of the pre-capture library preparation in up to 0.94
      (Pearson's test). Moreover, sequencing results showed that poor integrity DNA
      leads to high rates of false positive mutation calls, specially C:G>T:A and
      C:G>A:T. Poor quality FFPE DNA samples are prone to generating false positive
      mutation calls. These are especially perilous in cases in which subclonal
      populations are expected, such as in advance disease, since it could lead
      clinicians to erroneous conclusions and equivocated conduct.

PMID- 29175302
TI  - Matrix metalloproteinase and heparin-stimulated serine proteinase activities in
      post-prostate massage urine of men with prostate cancer.
AB  - Proteinases secreted by the prostate gland have a reproductive function in
      cleaving proteins in the ejaculate and in the female reproductive tract, but some
      may have a fundamental role in disease and pathological processes including
      cancer. The purpose of this study was to determine if there were differences in
      proteinase activities in urine samples collected following prostate massage of
      men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy
      determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase
      activities were detected using protein substrate zymography. There were no
      differences in activities of MMP-2, proMMP-9, and MMP-9/NGAL (neutrophil
      gelatinase associated lipocalin) complex (gelatin substrate) in men with detected
      prostate cancer, although the latter two were somewhat diminished. A caseinolytic
      activity of about 75kDa inhibited by calcium did not differ between the NEM and
      CaP groups. Heparin stimulated calcium sensitive gelatinolytic activities of
      approximately 22, 42, and 60kDa, but did not affect activities of MMP-2, MMP-9,
      or the 75kDa caseinolytic activity. The 22, 42, and 60kDa activities appear to be
      serine proteinases since they were inhibited by benzamidine. There was a
      significant decrease in the 22kDa heparin-stimulated serine proteinase activity
      in urines of men with cancer. Proteinase expression and activities, perhaps in
      combination with other potential markers, may prove useful in urine for detection
      and evaluation of prostate cancer.

PMID- 29175304
TI  - Age, sex, and TNF associated differences in the gut microbiota of mice and their
      impact on acute TNBS colitis.
AB  - Mouse models are often used to determine the interactions between the microbiota
      and inflammatory processes and overcome the confounding effect of the naturally
      high inter-individual variation of the gut microbiota in humans. However, the
      microbiomes of mice are also variable and data detailing the degree to which
      factors like mouse sex and age contribute to mouse gut microbiota variation is
      limited. Our objective was to determine the impact sex and age have on the mouse
      gut microbiota and the severity of acute 2, 4, 6-trinitrobenzenesulfonic acid
      (TNBS) induced colitis. We used Illumina sequencing of 16S rRNA genes to
      characterize the fecal microbiota of B6.129S wild-type (WT) mice and mice lacking
      tumor necrosis factor (Tnf-/-) before and after acute TNBS colitis. There were
      differences between the fecal microbiota of male and female WT mice as well as
      Tnf-/- mice, both pre-and post-colitis. Male WT mice had more severe colitis than
      female WT mice and Tnf-/- mice of both sexes. We also identified microbial taxa
      differences between 4-5 and 6-7-week old WT and Tnf-/- mice both pre-and post
      colitis. Here we provide evidence that the mouse fecal microbiome is shaped, in
      part, by sex, age and TNF production and that these effects correlate with the
      degree of animals' colitis.

PMID- 29175305
TI  - Balancing precision with inclusivity in meta-analyses: A response to Roos and
      colleagues (2017).
AB  - Roos and colleagues' commentary on our recent meta-analysis examining acute
      stress effects on executive functions is an important delineation of the limits
      of meta-analyses with heterogeneous outcomes. In this response, we wish to both
      clarify the inferences we feel are appropriate given the analyses and address the
      methodological concerns they raise. Additionally, we present new analyses that
      answer questions raised in their commentary. We first discuss the classification
      of a broad array of tasks that depend upon the same construct (e.g., inhibition)
      and note that this allows for inferences regarding the process that underpins all
      of those tasks, but this does not entail that all tasks dependent upon that
      construct will evidence the same effect of stress. Second, we argue that
      requiring that a study present a significant effect of stress on cortisol for
      inclusion in analyses is too stringent for a number of reasons (e.g., some
      studies using validated stressor paradigms correctly do not assay cortisol for
      budgetary reasons) and we present analyses showing that even when studies that
      did not present a cortisol response were removed, the initially observed effects
      still held. Finally, we address concerns raised regarding analyses of time
      dependent effects by presenting new analyses that help to allay those concerns.
      In sum, we applaud Roos and colleagues' exortation for greater methodological and
      conceptual rigor in studies of stress and executive function, and the additional
      analyses prompted by their questions help to clarify observed effects and further
      the field of stress and executive function research.

PMID- 29175303
TI  - EGFR, KRAS, BRAF and HER2 testing in metastatic lung adenocarcinoma: Value of
      testing on samples with poor specimen adequacy and analysis of discrepancies.
AB  - Molecular testing on metastatic lung adenocarcinoma or on non-small cell non
      squamous lung carcinoma often relies on small specimen. In this group of patient
      with poor specimen adequacy, we analyzed the rate of EGFR, KRAS, BRAF and HER2
      mutations compared to their rate in optimal specimen. We analyzed discrepancies
      in molecular testing results in patients with iterative analysis on several
      samples. We performed a retrospective study of 1538 samples consecutively
      analyzed. 263/665 (39,5%) biopsies and 37/708 (5,2%) surgical specimens were
      considered as samples with poor specimen adequacy (p<0,0001). A lower tumor cell
      content was associated with a lower rate of KRAS mutation: 15,8% in samples with
      <10% of tumor cells or <100 tumor cells versus 29,8% in samples with >10% tumor
      cell and >100 tumor cells (p=0,001). KRAS mutational rate was at 11,1% in
      cytology specimens, significantly lower than in biopsy or surgical specimens
      respectively at 28,2% and 28,5% (p=0,0002). Tumor cell content was not associated
      with mutational rate for EGFR, BRAF and HER2 mutations. DNA quantity was not
      associated with mutational rate for EGFR, KRAS, BRAF and HER2. A discrepancy in
      molecular testing was found in 16 patients. For 5 patients there was also a
      discrepancy for TTF-1 expression. On the 11 without TTF-1 discrepancy, specimen
      adequacy was not fulfilled in 10 cases at least for tumor content. Discrepancies
      were found in the case of low cellularity, poor cell content or testing on
      cytological specimens. Tumor cell content is a crucial parameter for molecular
      analysis rather than the type of specimen or the DNA quantity. Discrepancies in
      molecular testing results are rare but might suggest the presence of another
      tumor type, the emergence of another clone or a molecular testing in a sample
      with low cell content.

PMID- 29175306
TI  - Embodiment in the aging mind.
AB  - Bodily awareness is a central component of human sensation, action, and
      cognition. The human body is subject to profound changes over the adult lifespan.
      We live in an aging society: the mean age of people living in industrialized
      countries is currently over 40 years, and further increases are expected.
      Nevertheless, there is a lack of comprehensive knowledge that links changes in
      embodiment that occur with age to neuronal mechanisms and associated sensorimotor
      and cognitive deficits in older adults. Here, we synthesize existing evidence and
      introduce the NFL Framework of Embodied Aging, which links basic neuronal (N)
      mechanisms of age-related sensorimotor decline to changes in functional (F)
      bodily impairments, including deficits in higher-level cognitive functions, and
      impairments in daily life (L). We argue that cognitive and daily life impairments
      associated with old age are often due to deficits in embodiment, which can partly
      be linked to neuronal degradation at the sensorimotor level. The framework may
      encourage the development of novel approaches to improve autonomous living for
      older adults.

PMID- 29175307
TI  - Extracellular vesicles in obesity and diabetes mellitus.
AB  - Cell-to-cell communication happens via diverse mechanisms including the
      synthesis, release and transfer to target cells of extracellular vesicles (EVs).
      EVs include nanovesicles (i.e., exosomes) and microvesicles, including apoptotic
      bodies. The amount and cargo of released EVs, which consist of microRNAs
      (miRNAs), mRNA, proteins, DNA, among other molecules, are altered in obesity and
      diabetes mellitus. EVs from these diseases show with altered cargo including
      several miRNAs and the enrichment with molecules involved in inflammation, immune
      efficiency, and cell activation. The role of EVs in obesity regards with
      adipocytes-released vesicles that may end in a systemic insulin resistance. In
      diabetes mellitus, the exosomes cargo may signal to transform a normal phenotype
      into a diabetic phenotype in endothelial cells. The evidence of EVs as modulators
      of cell function is increasing; however, it is still unclear whether exosomes or
      microvesicles are a trustable and useful marker for the diagnose or early
      detection of obesity or diabetes mellitus. In this review, we summarise the
      reported information regarding EVs involvement in obesity, T1 and T2 diabetes
      mellitus, and gestational diabetes mellitus. We emphasise the fact that studies
      addressing a potential effect of obesity or diabetes mellitus on cell function
      and the severity of the diseases are done in patients suffering simultaneously
      with both of these diseases, i.e., diabesity. Unfortunately, the lack of
      information regarding the biological effects and the potential involved
      mechanisms makes difficult to understand the role of the EVs as a marker of these
      and perhaps other diseases.

PMID- 29175308
TI  - Differential use of danger and safety signals in an animal model of anxiety
      vulnerability: The behavioral economics of avoidance.
AB  - Differential processing of danger and safety signals may underlie symptoms of
      anxiety disorders and posttraumatic stress disorder. One symptom common to these
      disorders is pathological avoidance. The present study examined whether danger
      and safety signals influence avoidance differently in anxiety-vulnerable Wistar
      Kyoto (WKY) rats and Sprague Dawley (SD) rats. SD and WKY rats were tested in a
      novel progressive ratio avoidance task with and without danger or safety signals.
      Two components of reinforcement, hedonic value and motivation, were determined by
      fitting an exponentiated demand equation to the data. Hedonic value of avoidance
      did not differ between SD and WKY rats, but WKY rats had greater motivation to
      avoid than SD rats. Removal of the safety signal reduced motivation to avoid in
      SD, but not WKY, rats. Removal of the danger signal did not alter avoidance in
      either strain. When danger and safety signals were presented simultaneously, WKY
      rats responded to the danger signals, whereas SD rats responded to the safety
      signal. The results provide evidence that 1) safety signals enhance motivation to
      avoid in SD rats, 2) both danger and safety signals influence motivation in WKY
      rats, and 3) danger signals take precedence over safety signals when presented
      simultaneously in WKY rats. Thus, anxiety vulnerability is associated with
      preferential use of danger signals to motivate avoidance. The differential use of
      danger and safety signals has important implications for the etiology and
      treatment of pathological avoidance in anxiety disorders and posttraumatic stress
      disorder.

PMID- 29175310
TI  - No More 'Code Black': Intervention to Improve Inpatient Flow at a Large Public
      Hospital.

PMID- 29175311
TI  - Three of a (Peptic) Kind!

PMID- 29175309
TI  - Altered neuro-inflammatory gene expression in hippocampus in major depressive
      disorder.
AB  - Major Depressive Disorder (MDD) is a common psychiatric disorder for which
      available medications are often not effective. The high prevalence of MDD and
      modest response to existing therapies compels efforts to better understand and
      treat the disorder. Decreased hippocampal volume with increasing duration of
      depression suggests altered gene expression or even a decrease in neurogenesis.
      Tissue punches from the dentate gyrus were collected postmortem from 23 subjects
      with MDD and 23 psychiatrically-normal control subjects. Total RNA was isolated
      and whole transcriptome paired-end RNA-sequencing was performed using an Illumina
      NextSeq 500. For each sample, raw RNA-seq reads were aligned to the Ensembl
      GRCh38 human reference genome. Analysis revealed 30 genes differentially
      expressed in MDD compared to controls (FDR<0.05). Down-regulated genes included
      several with inflammatory function (ISG15, IFI44L, IFI6, NR4A1/Nur-77) and GABBR1
      while up-regulated genes included several with cytokine function (CCL2/MCP-1),
      inhibitors of angiogenesis (ADM, ADAMTS9), and the KANSL1 gene, a histone
      acetyltransferase. Similar analyses of specific subsets of MDD subjects (suicide
      vs. non-suicide, single vs. multiple episodes) yielded similar, though not
      identical, results. Enrichment analysis identified an over-representation of
      inflammatory and neurogenesis-related (ERK/MAPK) signaling pathways significantly
      altered in the hippocampal dentate gyrus in MDD. Together, these data implicate
      neuro-inflammation as playing a crucial role in MDD. These findings support
      continued efforts to identify adjunctive approaches towards the treatment of MDD
      with drugs including anti-inflammatory and neuroprotective properties.

PMID- 29175312
TI  - Splenic Rupture After Same Level Fall.

PMID- 29175313
TI  - Relevance of the chaperone-like protein calreticulin for the biological behavior
      and clinical outcome of cancer.
AB  - The death of cancer cells can be categorized as either immunogenic (ICD) or
      nonimmunogenic, depending on the initiating stimulus. The immunogenic processes
      of immunogenic cell death are mainly mediated by damage-associated molecular
      patterns (DAMPs), which include surface exposure of calreticulin (CRT), secretion
      of adenosine triphosphate (ATP), release of non-histone chromatin protein high
      mobility group box 1 (HMGB1) and the production of type I interferons (IFNs).
      DAMPs are recognized by various receptors that are expressed by antigen
      presenting cells (APCs) and potentiate the presentation of tumor antigens to T
      lymphocytes. Accumulating evidence indicates that CRT exposure constitutes one of
      the major checkpoints, that determines the immunogenicity of cell death both in
      vitro and in vivo in mouse models. Moreover, recent studies have identified CRT
      expression on tumor cells not only as a marker of ICD and active anti-tumor
      immune reactions but also as a major predictor of a better prognosis in various
      cancers. Here, we discuss the recent information on the CRT capacity to activate
      anticancer immune response as well as its prognostic and predictive role for the
      clinical outcome in cancer patients.

PMID- 29175314
TI  - Immunomodulatory properties of umbilical cord vein mesenchymal stromal cells
      influenced by gestational age and in vitro expansion.
AB  - In vivo and in vitro aging of the mesenchymal stromal cells (MSCs) can affects
      their properties. We investigated the immunomodulatory properties of the term and
      preterm human umbilical cord vein MSCs (UCV-MSCs) at the passages (P) 2 and 5.
      Term and preterm UCV-MSCs at P2 and 5 were co-cultured with two-way mixed
      lymphocyte reaction. Proliferation, IFN-gamma and IL-10 protein levels, mRNA
      levels of the COX-2, TGF-beta1, TNF-alpha, IL-4 and FoxP3 were assessed. The term
      UCV-MSCs and P5 of the term and preterm UCV-MSCs had stronger inhibitory effects
      on cell proliferation than the preterm UCV-MSC and P2, respectively (P = 0.001).
      In supernatants of the co-cultures, IFN-gamma was higher in the term UCV-MSC than
      the preterm UCV-MSC, while IL-10 was higher in the preterm UCV-MSCs than the term
      UCV-MSCs. Also in the co-cultures, COX-2 expression in the term UCV-MSCs and P2
      was higher than the preterm UCV-MSCs and P5, respectively and TGF-beta1
      expression in the term UCV-MSCs was higher than preterm. Conclusively it appears
      that the term UCV-MSCs, and P5 of the term and preterm UCV-MSCs showed a higher
      immunomodulatory ability than the preterm UCV-MSCs and P2, respectively.

PMID- 29175315
TI  - Flagellin increases death receptor-mediated cell death in a RIP1-dependent
      manner.
AB  - Efficient adjuvants have the potential to trigger both innate and adaptive immune
      responses simultaneously. Flagellin is a unique pathogen-derived protein, which
      is recognized by pattern recognition receptors (PRRs) as well as by B-cell and T
      cell receptors thus providing an important link between innate and adaptive
      immunity. The aforementioned properties define flagellin as an optimal adjuvant.
      The induction of immunogenic cell death could be an additional expectation for
      adjuvants in the context of cancer immunotherapy due to their ability to activate
      dendritic cells (DC) to present tumor antigens through the engulfment of dying
      cells. The immunostimulatory potential of flagellin in the course of DC and
      lymphocyte activation is well documented, however the exact mechanism is not
      fully explored. Based on this limitation we sought to investigate the potential
      modulatory effects of flagellin on various cell death processes knowing that it
      plays detrimental roles in regulating the final outcome of various types of
      immune responses. Here we provide evidence that the pre-treatment of Jurkat T
      cells with recombinant flagellin is able to increase the degree of cell death
      provoked by FasL or TNF-alpha, and concomitantly increases the cytotoxic
      potential of phytohemagglutinin activated T-lymphocytes in a TLR5 dependent way.
      In contrast to these flagellin-mediated effects on the death receptor-induced
      signaling events, the mitochondrial apoptotic pathway remained unaffected.
      Furthermore, the cell culture supernatant of wild type Salmonella enteritidis
      bacteria, but not their flagellin deficient variant, was able to enhance the Fas
      induced cell death process. To define the molecular mechanisms of flagellin
      mediated elevated levels of cell death we were able to detect the upregulation of
      RIP1-dependent signaling events. These findings demonstrate that the cooperative
      actions of pattern recognition and different death receptors are able to initiate
      the cell death process with the mobilization of RIP-dependent cell death
      modalities. This finding highlights the capability of flagellin to act as a
      potential adjuvant which is relevant for tumor immunotherapy.

PMID- 29175317
TI  - Epitope identification of specific naturally occurring human anti-avidin
      antibodies.
AB  - Human serum contains natural antibodies against avidin. Affinity purified natural
      anti-avidin human IgG exhibits affinity constants comparable to those of
      antibodies produced by active immunization of rabbits. Using a random hexapeptide
      library displayed on the filamentous M13 phage, and rabbit anti-avidin purified
      antibodies as a selector, we searched for epitopes shared by both selector and
      natural human anti-avidin IgG. This approach, enabled the isolation and
      identification of phagotopes bearing consensus motifs similar to sequence
      stretches of the avidin loops and beta-sheet regions. These phagotopes were
      recognized by the natural human anti-avidin antibodies. The fact that natural
      anti-avidin antibodies in human serum have similar epitopes to those of IgG
      elicited by active immunization of animals, led us to suggest that small peptide
      epitopes may prevent deleterious effects caused by antibodies formed against food
      proteins as well as therapeutic proteins.

PMID- 29175316
TI  - Inhibition of tumor growth by mouse ROR1 specific antibody in a syngeneic mouse
      tumor model.
AB  - INTRODUCTION: Immunotherapy with tumor-associated antigens (TAAs) is a
      potentially powerful approach to eradicate tumor cells. The receptor tyrosine
      kinase-like orphan receptor 1 (ROR1) plays a crucial role for survival of tumor
      cells and is overexpressed in various malignancies. In the present study, we
      developed a syngeneic mouse tumor model to assess anti-tumor effect of mouse ROR1
      specific polyclonal antibody (pAb) in vivo. MATERIALS AND METHODS: Mouse ROR1
      specific antibody was produced in rabbit using recombinant ROR1 protein. Tow
      mouse tumor cell lines, (4T1 and CT26), were transfected with full length mouse
      ROR1 construct and stable clones were selected and characterized by
      immunocytochemistry, Western blot and flow cytometry. In vitro and in vivo anti
      tumor activities of anti-ROR1 antibody were assessed by XTT and syngeneic BALB/c
      mouse model, respectively. RESULTS: We successfully established two mouse ROR1
      overexpressing tumor cell lines. The in vitro results indicate that the ROR1pAb
      did not significantly inhibit growth of ROR1+ cell lines. One of these cell lines
      (CT26-ROR1) was implanted in syngeneic BALB/c mice to assess anti-ROR1 tumor
      inhibitory activity in vivo. The tumor size was significantly reduced in mice
      treated with ROR1 specific pAb. CONCLUSION: Our results demonstrated for the
      first time tumor inhibitory effect of mouse ROR1 specific antibody in a syngeneic
      mouse tumor model. This model is a promising tool for preclinical assessment of
      ROR1 therapeutics and investigation of the underling molecular mechanisms.

PMID- 29175318
TI  - Effectiveness of a blended learning course and flipped classroom in first year
      anaesthesia training.
AB  - BACKGROUND: Blended learning, which combines internet-based platform and
      lecturing, is used in anaesthesiology and critical care teaching. However, the
      benefits of this method remain unclear. METHODS: We conducted a prospective,
      multicentre, non-randomised work between 2007 and 2014 to study the effect of
      blended learning on the results of first year anaesthesia and critical care
      residents in comparison with traditional teaching. Blended learning was
      implemented in Rouen University Hospital in 2011 and residents affiliated to this
      university corresponded as the blended learning group. The primary outcome was
      the resident's results as measured with multiple-choice questions between blended
      learning and control groups after beginning blended learning (post-interventional
      stage). The secondary outcomes included residents' results between pre and post
      interventional stages and homework's time. Moreover, comparison between control
      and blended learning group before beginning blended learning (pre-interventional
      stage) was performed. RESULTS: From 2007 to 2014, 308 residents were included.
      For the pre-interventional period, the mean score in the blended learning group
      (n=53) was 176 (CI 95% 163 to 188) whereas the mean score in the control group
      (n=106) was 167 (CI 95% 160 to 174) (no difference). For the post-interventional
      period, the mean score in blended learning group (n=54) was 232 on 300 (CI95% 227
      237) whereas the mean score in the control group (n=95) is 215 (CI95% 209-220)
      (P<0.001). In the two groups, comparison between pre and post-interventional
      stages showed the increase of mean score, stronger for blended learning group
      (32% and 28% in blended learning and control group, P<0.05). The average time of
      homework in the blended learning group was 27h (CI 95% 18.2-35.8) and 10h in the
      control group (CI 95% 2-18) (P<0.05). CONCLUSIONS: This work suggests the
      positive effect of blended learning (associating internet-based learning and
      flipped classroom) on the anaesthesia and critical care residents' knowledge by
      increasing their homework's time.

PMID- 29175319
TI  - SHANK genes in autism: Defining therapeutic targets.

PMID- 29175320
TI  - Mitochondrial activity in the regulation of stem cell self-renewal and
      differentiation.
AB  - Mitochondria are classically known as the essential energy producers in cells. As
      such, the activation of mitochondrial metabolism upon cellular differentiation
      was deemed a necessity to fuel the high metabolic needs of differentiated cells.
      However, recent studies have revealed a direct role for mitochondrial activity in
      the regulation of stem cell fate and differentiation. Several components of
      mitochondrial metabolism and respiration have now been shown to regulate
      different aspects of stem cell differentiation through signaling,
      transcriptional, proteomic and epigenetic modulations. In light of these findings
      mitochondrial metabolism is no longer considered a consequence of cellular
      differentiation, but rather a key regulatory mechanism of this process. This
      review will focus on recent progress that defines mitochondria as the epicenters
      for the regulation of stem cell fate decisions.

PMID- 29175321
TI  - Methods for lineage tracing on the organism-wide level.
AB  - Determining the lineage origin of cell types is a major goal in developmental
      biology. Furthermore, lineage tracing is a powerful approach for understanding
      the origin of developmental defects as well as the origin of diseases such as
      cancer. There is now a variety of complementary approaches for identifying
      lineage relationships, ranging from direct observation of cell divisions by light
      microscopy to genetic labeling of cells using inducible recombinases and
      fluorescent reporters. A recent development, and the main topic of this review
      article, is the use of high-throughput sequencing data for lineage analysis. This
      emerging approach holds the promise of increased multiplexing capacity, allowing
      lineage analysis of large cell numbers up to the organism-wide level combined
      with simultaneous transcription profiling by single cell RNA sequencing.

PMID- 29175322
TI  - Illuminating information transfer in signaling dynamics by optogenetics.
AB  - Cells receive diverse signaling cues from their environment that trigger cascades
      of biochemical reactions in a dynamic manner. Single-cell imaging technologies
      have revealed that not only molecular species but also dynamic patterns of
      signaling inputs determine the fates of signal-receiving cells; however it has
      been challenging to elucidate how such dynamic information is delivered and
      decoded in complex networks of inter-cellular and inter-molecular interactions.
      The recent development of optogenetic technology with photo-sensitive proteins
      has changed this situation; the combination of microscopy and optogenetics
      provides fruitful insights into the mechanism of dynamic information processing
      at the single-cell level. Here, we review recent efforts to visualize the flows
      of dynamic patterns in signaling pathways, which utilize methods integrating
      single-cell imaging and optogenetics.

PMID- 29175323
TI  - Isolation and characterization of ventricular-like cells derived from NKX2
      5eGFP/w and MLC2vmCherry/w double knock-in human pluripotent stem cells.
AB  - Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) are a promising
      source for cell transplantation into the damaged heart, which has limited
      regenerative ability. Many methods have been developed to obtain large amounts of
      functional CMs from hPSCs for therapeutic applications. However, during the
      differentiation process, a mixed population of various cardiac cells, including
      ventricular, atrial, and pacemaker cells, is generated, which hampers the proper
      functional analysis and evaluation of cell properties. Here, we established NKX2
      5eGFP/w and MLC2vmCherry/w hPSC double knock-ins that allow for labeling,
      tracing, purification, and analysis of the development of ventricular cells from
      early to late stages. As with the endogenous transcriptional activities of these
      genes, MLC2v-mCherry expression following NKX2-5-eGFP expression was observed
      under previously established culture conditions, which mimic the in vivo cardiac
      developmental process. Patch-clamp and microelectrode array electrophysiological
      analyses showed that the NKX2-5 and MLC2v double-positive cells possess
      ventricular-like properties. The results demonstrate that the NKX2-5eGFP/w and
      MLC2vmCherry/w hPSCs provide a powerful model system to capture region-specific
      cardiac differentiation from early to late stages. Our study would facilitate
      subtype-specific cardiac development and functional analysis using the hPSC
      derived sources.

PMID- 29175324
TI  - Lixisenatide reduces amyloid plaques, neurofibrillary tangles and
      neuroinflammation in an APP/PS1/tau mouse model of Alzheimer's disease.
AB  - Type 2 diabetes mellitus (T2DM) has been identified as a high risk factor for
      Alzheimer's disease (AD). The impairment of insulin signaling has been found in
      AD brain. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, normalises
      insulin signaling and acts as a neuroprotective growth factor. We have previously
      shown that the long-lasting GLP-1 receptor (GLP-1R) agonist lixisenatide plays an
      important role in memory formation, synaptic plasticity and cell proliferation of
      rats. In the follow-up study, we analysed the neuroprotective effect and
      mechanism of lixisenatide, injected for 60 days at 10 nmol/kg i.p. once daily in
      APP/PS1/tau female mice and C57BL/6J female mice (as control) aged 12 month. The
      results showed that lixisenatide could reduce amyloid plaques, neurofibrillary
      tangles and neuroinflammation in the hippocampi of 12-month-old APP/PS1/tau
      female mice; activation of PKA-CREB signaling pathway and inhibition of p38-MAPK
      might be the important mechanisms in the neuroprotective function of
      lixisenatide. The study demonstrated that GLP-1R agonists such as lixisenatide
      might have the potential to be developed as a novel therapy for AD.

PMID- 29175325
TI  - Fatty acid oxidation alleviates the energy deficiency caused by the loss of MPC1
      in MPC1+/- mice.
AB  - Pyruvate is a central substrate in energy metabolism, paramount to carbohydrate,
      fat, and amino acid catabolic and anabolic pathways. Mitochondrial pyruvate
      carrier 1(MPC1) is one important component of the complex that facilitates
      mitochondrial pyruvate import. Complete MPC1 deficiency is a serious concern, and
      has been shown to result in embryonic lethality in mice. The study outlined in
      this paper generated one mouse line with the MPC1 protein part deficiency by
      using the CRISPR/Cas9 system. Clinical observations, body weight and organ/tissue
      weight, gas exchange, cold-stimulation, blood parameters, as well as
      histopathology analysis were analyzed to evaluate potential physiological
      abnormalities caused by MPC1 deficiency. Results indicate that MPC1+/- mice
      experienced a change in important clinical criteria such as low body weight,
      decreased movement, and low body shell temperature, few adipose accumulate. The
      mice show significant difference in some blood parameters including apo-B100, apo
      A1, HDL, glucagon, insulin. However these changes alleviated while being fed with
      the HFD, which provided metabolites to sustain the TCA cycle and body
      development. The MPC1+/- mice may employ fatty acid oxidation to meet their
      bioenergetic demands. This study suggests that inhibition of MPC1 activity can
      boost fatty acid oxidation to provide sufficient energy to the body. This work
      promotes further studies regarding the interplay between carbohydrate and fat
      metabolism.

PMID- 29175326
TI  - Downregulation of Nedd4L predicts poor prognosis, promotes tumor growth and
      inhibits MAPK/ERK signal pathway in hepatocellular carcinoma.
AB  - Accumulating evidence indicates that the neural precursor cell-expressed,
      developmentally downregulated 4-like (Nedd4L) related with some tumor progression
      pathways and was found abnormally expressed in several kinds of solid cancers.
      However, the role and mechanism of Nedd4L in HCC remain unknown. This study was
      to assess the role of Nedd4L in HCC tumorigenesis and prognosis. The real-time
      quantitative RT-PCR and immunohistochemistry results revealed that Nedd4L was
      downregulated in HCC tissues compared to corresponding peri-noncancerous tissue,
      and HCC patients with low expression of Nedd4L exhibited poor prognosis assessed
      by Kaplan-Meier and Cox regression analysis in 78 HCC patients. Furthermore,
      knockdown of Nedd4L could significantly promote proliferation of HCC cells by CCK
      8 and colony formation assays in vitro; whereas ectopic expression of Nedd4L
      resulted in attenuating proliferation in vitro and tumor growth in vivc
      determined by nude mice xenografts model. Mechanically, Nedd4L could
      phosphorylate ERK1/2 and regulate genes related with apoptosis. Collectively,
      Nedd4L plays a tumor suppressive role in HCC, possibly through triggering
      MAPK/ERK-mediated apoptosis, and Nedd4L downregulation may be a potential
      prognostic biomarker as well as a therapeutic target for HCC.

PMID- 29175327
TI  - Structural basis for the interaction between DJ-1 and Bcl-XL.
AB  - DJ-1 is a multifunctional protein associated with Parkinson's disease (PD) and
      tumorigenesis. In response to ultraviolet B (UVB) irradiation, DJ-1 is
      translocated into the mitochondria, and its interaction with the mitochondrial
      protein Bcl-XL protects cells against death. In this study, we characterized the
      molecular interaction between DJ-1 and Bcl-XL by NMR spectroscopy. The NMR
      chemical shift perturbation data demonstrated that the oxidized but not the
      reduced form of DJ-1 binds to the predominantly hydrophobic groove surrounded by
      the BH1-BH3 domains in Bcl-XL. In addition, our results showed that the C
      terminal alpha8-helix peptide (Cpep) of DJ-1 binds to the pro-apoptotic BH3
      peptide-binding hydrophobic groove in Bcl-XL and, thus, acts as a Bcl-XL-binding
      motif. In combination with the NMR chemical shift perturbation data, a refined
      structural model of the Bcl-XL/DJ-1 Cpep complex revealed that the binding mode
      is remarkably similar to that of other Bcl-XL/pro-apoptotic BH3 peptide
      complexes. Taken together, our results provide a structural basis for the binding
      mechanism between DJ-1 and Bcl-XL, which will contribute to molecular
      understanding of the role of mitochondrial DJ-1 in Bcl-XL regulation in response
      to oxidative stress.

PMID- 29175328
TI  - Construction of a high-yield dengue virus by replacing nonstructural proteins 3
      4B without increasing virulence.
AB  - Producing virus at high yield is critically important for development of whole
      virion inactivated vaccines or live attenuated vaccines. Most dengue virus (DENV)
      clinical isolates, however, replicate at low levels in cultured cells, which
      limits their use for vaccine development. The present study examined differences
      between low-replicating DENV clinical isolates and high-replicating laboratory
      strains with the aim of engineering high-yield DENV clinical isolates.
      Construction of a series of recombinant chimeric viruses derived from a high
      replicating laboratory DENV type 4 (DENV-4) H241 strain and a clinical isolate
      revealed that the NS3-NS4B region of H241 conferred a replication advantage in
      cultured cells. Furthermore, northern blot analysis revealed that this advantage
      was due to more efficient synthesis of viral RNA. Importantly, replacement of the
      NS3-NS4B region of H241 did not increase virulence in mice, suggesting that viral
      production can be increased safely. This study provided information that will
      facilitate engineering of safe and high-yield viruses that can be used for
      vaccine development.

PMID- 29175329
TI  - Inhibition of CIP2A attenuates tumor progression by inducing cell cycle arrest
      and promoting cellular senescence in hepatocellular carcinoma.
AB  - CIP2A is a recent identified oncogene that inhibits protein phosphatase 2A (PP2A)
      and stabilizes c-Myc in cancer cells. To investigate the potential oncogenic role
      and prognostic value of CIP2A, we comprehensively analyzed the CIP2A expression
      levels in pan-cancer and observed high expression level of CIP2A in majority
      cancer types, including hepatocellular carcinoma (HCC). Based on a validation
      cohort including 60 HCC and 20 non-tumorous tissue samples, we further confirmed
      the high mRNA and protein expression levels of CIP2A in HCC, and found high CIP2A
      mRNA expression level was associated with unfavorable overall and recurrence-free
      survival in patients with HCC. Mechanistic investigations revealed that
      inhibition of CIP2A significantly attenuated cellular proliferation in vitro and
      tumourigenicity in vivo. Bioinformatic analysis suggested that CIP2A might be
      involved in regulating cell cycle. Our experimental data further confirmed CIP2A
      knockdown induced cell cycle arrest at G1 phase. We found accumulated cellular
      senescence in HCC cells with CIP2A knockdown, companying expression changes of
      senescence associated proteins (p21, CDK2, CDK4, cyclin D1, MCM7 and FoxM1).
      Mechanistically, CIP2A knockdown repressed FoxM1 expression and induced FoxM1
      dephosphorylation. Moreover, inhibition of PP2A by phosphatase inhibitor rescued
      the repression of FoxM1. Taken together, our results showed that CIP2A was highly
      expressed in HCC. Inhibition of CIP2A induced cell cycle arrest and promoted
      cellular senescence via repressing FoxM1 transcriptional activity, suggesting a
      potential anti-cancer target for patients with HCC.

PMID- 29175330
TI  - Activation of AMP-activated protein kinase by compound 991 protects osteoblasts
      from dexamethasone.
AB  - Dexamethasone (Dex) induces direct cytotoxicity to cultured osteoblasts. The
      benzimidazole derivative compound 991 ("C991") is a novel and highly-efficient
      AMP-activated protein kinase (AMPK) activator. Here, in both MC3T3-E1
      osteoblastic cells and primary murine osteoblasts, treatment with C991 activated
      AMPK signaling, and significantly attenuated Dex-induced apoptotic and non
      apoptotic cell death. AMPKalpha1 knockdown (by shRNA), complete knockout (by
      CRISPR/Cas9 method) or dominant negative mutation (T172A) not only blocked C991
      mediated AMPK activation, but also abolished its pro-survival effect against Dex
      in osteoblasts. Further studies showed that C991 boosted nicotinamide adenine
      dinucleotide phosphate (NADPH) activity and induced mRNA expression of NF-E2
      related factor 2 (Nrf2)-regulated genes (heme oxygenase-1 and NADPH quinone
      oxidoreductase 1). Additionally, C991 alleviated Dex-induced reactive oxygen
      species (ROS) production in osteoblasts. Notably, genetic AMPK inhibition
      reversed the anti-oxidant actions by C991 in Dex-treated osteoblasts. Together,
      we conclude that C991 activates AMPK signaling to protect osteoblasts from Dex.

PMID- 29175331
TI  - Involvement of TRPV3 and TRPM8 ion channel proteins in induction of mammalian
      cold-inducible proteins.
AB  - Cold-inducible RNA-binding protein (CIRP), RNA-binding motif protein 3 (RBM3) and
      serine and arginine rich splicing factor 5 (SRSF5) are RNA-binding proteins that
      are transcriptionally upregulated in response to moderately low temperatures and
      a variety of cellular stresses in mammalian cells. Induction of these cold
      inducible proteins (CIPs) is dependent on transient receptor potential (TRP) V4
      channel protein, but seems independent of its ion channel activity. We herein
      report that in addition to TRPV4, TRPV3 and TRPM8 are necessary for the induction
      of CIPs. We established cell lines from the lung of TRPV4-knockout (KO) mouse,
      and observed induction of CIPs in them by western blot analysis. A TRPV4
      antagonist RN1734 suppressed the induction in wild-type mouse cells, but not in
      TRPV4-KO cells. A TRPV3 channel blocker S408271 and a TRPM8 channel blocker AMTB
      as well as siRNAs against TRPV3 and TRPM8 suppressed the CIP induction in mouse
      TRPV4-KO cells and human U-2 OS cells. A TRPV3 channel agonist 2-APB induced CIP
      expression, but camphor did not. Neither did a TRPM8 channel agonist WS-12. These
      results suggest that TRPV4, TRPV3 and TRPM8 proteins, but not their ion channel
      activities are necessary for the induction of CIPs at 32  degrees C.
      Identification of proteins that differentially interact with these TRP channels
      at 37  degrees C and 32  degrees C would help elucidate the underlying mechanisms
      of CIP induction by hypothermia.

PMID- 29175332
TI  - Ankyrin repeats as a dimerization module.
AB  - Legionella pneumophila is a pathogen, causing severe pneumonia in humans called
      Legionnaires' disease. AnkC (LegA12) is a poorly characterized 495-residue
      effector protein conserved in multiple Legionella species. Here, we report the
      crystal structure of a C-terminally truncated AnkC (2-384) at 3.2 A resolution.
      The structure shows seven ankyrin repeats (ARs) with unique structural features.
      AnkC forms a dimer along the outer surface of loops between ARs. The dimer exists
      both in the crystal form and in solution, as shown by analytical
      ultracentrifugation. This is the first example of ARs as a dimerization module as
      opposed to solely a protein interaction domain. In addition, a novel alpha-helix
      insert between AR3-AR4 is positioned across the surface opposite the ankyrin
      groove. Sequence conservation suggests that the ankyrin groove of AnkC is a
      functional site that interacts with binding targets. This ankyrin domain
      structure is an important step towards a functional characterization of AnkC.

PMID- 29175333
TI  - Distinct roles of Rheb and Raptor in activating mTOR complex 1 for the self
      renewal of hematopoietic stem cells.
AB  - The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) senses a cell's
      energy status and environmental levels of nutrients and growth factors. In
      response, mTORC1 mediates signaling that controls protein translation and
      cellular metabolism. Although mTORC1 plays a critical role in hematopoiesis, it
      remains unclear which upstream stimuli regulate mTORC1 activity in the context of
      hematopoietic stem cells (HSC) maintenance in vivo. In this study, we
      investigated the function of Rheb, a critical regulator of mTORC1 activity
      controlled by the PI3K-AKT-TSC axis, both in HSC maintenance in mice at steady
      state and in HSC-derived hematopoiesis post-transplantation. In contrast to the
      severe hematopoietic dysfunction caused by Raptor deletion, which completely
      inactivates mTORC1, Rheb deficiency in adult mice did not show remarkable
      hematopoietic failure. Lack of Rheb caused abnormalities in myeloid cells but did
      not have impact on hematopoietic regeneration in mice subjected to injury by
      irradiation. As previously reported, Rheb deficiency resulted in defective HSC
      derived hematopoiesis post-transplantation. However, while Raptor is essential
      for HSC competitiveness in vivo, Rheb is dispensable for HSC maintenance under
      physiological conditions, indicating that the PI3K-AKT-TSC pathway does not
      contribute to mTORC1 activity for sustaining HSC self-renewal activity at steady
      state. Thus, the various regulatory elements that impinge upstream of mTORC1
      activation pathways are differentially required for HSC homeostasis in vivo.

PMID- 29175334
TI  - Management of Brodie bite: Note on surgical treatment.
AB  - Described and illustrated by Allan G. Brodie in 1946, Brodie's syndrome
      corresponds to an abnormal transverse occlusal relationship in which the palatal
      cusps of the upper molars lie outside the vestibular cusps of their mandibular
      antagonists. This article covers the diagnosis, clinical presentation, etiology
      (and, particularly, etiopathogenesis) and evolution of this syndrome, and also
      its management, which is often difficult. The main limitations and difficulties
      of orthodontics and surgery are presented, along with the surgical techniques
      used. These points are illustrated by some clinical cases highlighting the
      importance of three-dimensional analyses and 3D planning.

PMID- 29175335
TI  - ?

PMID- 29175336
TI  - Simultaneous flow cytometric immunophenotyping of necroptosis, apoptosis and RIP1
      dependent apoptosis.
AB  - Flow cytometry was been widely used to measure apoptosis for many decades but the
      researcher has no definitive way of determining other forms of cell death using
      this technology. The use of Western Blot technology has numerous drawbacks in
      that all the cells in the sample whether live, dead or maybe undergoing multiple
      discrete forms of cell death are analysed as one population. Flow cytometry given
      that it can analyse different sub-populations of cells within a sample would
      reveal the expression of cell death markers within these sub-populations rather
      than just give a single result from the entire population. Here we describe a
      flow cytometric assay fully realising that potential by the use of anti-RIP-3
      (Receptor-interacting serine/threonine-protein kinase 3) and anti-active caspase
      3 fluorescently tagged antibodies and a fixable live dead fluorescent dye. This
      allows the determination of the degree of necroptosis, apoptosis and RIP1
      dependent apoptosis within live and dead populations. Necroptosis was identified
      by the up-regulation of RIP3, while RIP1-dependent apoptosis was described by
      double positive for RIP3/active Caspase-3 events in live and dead populations.
      Apoptotic cells were defined by an active-Caspase-3+ve/RIP3-ve phenotype. Pan
      caspase blocker zVAD and RIP1 inhibitors GSK'481 or necrostatin-1 revealed
      interesting modulations of such sub-populations of Jurkat cells. This novel flow
      cytometric assay employing two antibodies and a fixable viability probe provides
      the researcher with in-depth analysis of various forms of regulated forms of cell
      death beyond what is currently available and is a major methodological
      advancement in this field.

PMID- 29175337
TI  - Unraveling complex nanoscale lipid dynamics in simple model biomembranes:
      Insights from fluorescence correlation spectroscopy in super-resolution
      stimulated emission depletion mode.
AB  - Dynamic heterogeneity (DH) at nanoscale due to lipid-lipid and/or lipid-protein
      interactions in cell membranes plays a crucial role in determining a broad range
      of important cell functions. In cell membranes, the dimensions of these
      nanodomains have been postulated to be in the order of 10's of nm and transient
      in nature. While the structural features of membranes have been studied in
      detail, little is known about their dynamical characteristics due to paucity of
      techniques which can probe nanoscale phenomena with simultaneous high temporal
      resolution. A combination of super-resolution stimulated emission depletion
      (STED) and fluorescence correlation spectroscopy (FCS) technique can overcome
      this limitation and provide information about the nanoscale dynamic heterogeneity
      in cell membranes. Using STED-FCS and FCS diffusion law, we provide an
      understanding of how nanoscale dynamically organizing lipid platforms can emerge
      in minimal system of model biomembranes. To illustrate the utility of the
      technique we have chosen cholesterol containing supported lipid bilayers and
      demonstrated the role of cholesterol concentration and/or added pore-forming
      protein, Listeriolysin O (LLO) in determining onset of lipid DH. In addition we
      have also looked at multi-component lipid bilayers with and without cholesterol
      to infer about the role of phospholipid and cholesterol composition on lipid
      dynamics. These results on simple biomimetic systems provide insights into
      fundamental pathways for the emergence of complex nanodomain substructures with
      implications for a wide variety of membrane mediated cellular events and depict
      the significant contribution that STED-FCS can make in resolving several
      outstanding issues in membrane biology.

PMID- 29175339
TI  - Molecular mechanisms of deformability of Plasmodium-infected erythrocytes.
AB  - In physiological conditions, normal erythrocytes are highly deformable due to
      their high surface area to volume ratio, their moderate cytoplasmic viscosity and
      the elasticity of their membrane skeleton. Infection with the human malaria
      parasite Plasmodium falciparum induces dramatic changes in cellular deformability
      and membrane elasticity of their host erythrocyte, in part due to the shape and
      the volume of the parasite itself, and to the export of parasite proteins that
      interact with host membrane skeletal proteins. These changes in deformability are
      tightly regulated by the parasite and may reflect a strategy to adapt to
      mechanical constraints encountered by the parasite in the human host. The
      molecular mechanisms underpinning regulation of deformability of P. falciparum
      infected erythrocytes are multifactorial and are being elucidated.

PMID- 29175338
TI  - Host-microbe interactions: commensal fungi in the gut.
AB  - Fungi are ubiquitous microbes that are common in diverse environments including
      as commensal organisms on the human body. In addition to its obvious role as a
      digestive organ, the intestines have been further appreciated as important for
      the development, maintenance, and instruction of the immune system. The gut
      harbors many types of microorganisms including bacteria, archaea, fungi, and
      viruses, and many studies over the past couple of decades have documented an
      important role for intestinal bacteria in immunological function. Recent studies
      are now suggesting that intestinal fungi (the gut 'mycobiome') may similarly play
      important roles in host immunity and inflammation. This review will discuss
      recent studies that will influence our growing understanding of the role(s) of
      intestinal fungi in health and disease.

PMID- 29175340
TI  - Membrane trafficking and remodeling at the host-parasite interface.
AB  - Membrane shape is functionally linked with many cellular processes. The limiting
      membrane of vacuoles containing Toxoplasma gondii and Plasmodium apicomplexan
      parasites lies at the host-parasite interface. This membrane comprises intra
      vacuolar and extra-vacuolar tubulo-vesicular deformations, which influence host
      parasite cross-talk. Here, underscoring specificities and similarities between
      the T. gondii and Plasmodium contexts, we present recent findings about vacuolar
      membrane remodeling and its potential roles in parasite fitness and immune
      recognition. We review in particular the implication of tubulo-vesicular
      structures in trapping and/or transporting host and parasite components.
      Understanding how membrane remodeling influences host-pathogen interactions is
      expected to be critical in the battle against many intracellular pathogens beyond
      parasites.

PMID- 29175341
TI  - Forecasting the burden of type 2 diabetes mellitus in Qatar to 2050: A novel
      modeling approach.
AB  - AIMS: We developed and demonstrated a novel mathematical modeling approach to
      forecast the burden of type 2 diabetes mellitus (T2DM) and to investigate T2DM
      epidemiology for the purpose of informing public health policy and programming.
      METHODS: A population-level compartmental mathematical model was constructed and
      applied to Qatar. The model was stratified according to sex, age group, risk
      factor status, and T2DM status, and was parameterized by nationally
      representative data. RESULTS: T2DM prevalence increased from 16.7% in 2012 to at
      least 24.0% by 2050. The rise in T2DM was most prominent among 45-54 years old.
      T2DM health expenditure was estimated to increase by 200-600% and to account for
      up to 32% of total health expenditure by 2050. Prevalence of obesity, smoking,
      and physical inactivity was predicted to increase from 41.4% to 51.0%, from 16.4%
      to 19.4%, and from 45.9% to 53.0%, respectively. The proportion of T2DM incidence
      attributed to obesity, smoking and physical inactivity was estimated at 57.5%,
      1.8%, and 5.4%, respectively in 2012, and 65.7%, 2.1%, and 6.0%, respectively in
      2050. Exploring different scenarios for the trends in risk factors, T2DM
      prevalence reached up to 37.7% by 2050. CONCLUSIONS: Using our innovative
      approach, a rising T2DM epidemic is predicted to continue in the next decades,
      driven by population growth, ageing and adverse trends in risk factors. Obesity
      was the principal risk factor explaining two-thirds of T2DM incidence. T2DM must
      be a national priority addressed by preventive and therapeutic interventions
      targeting T2DM and its modifiable risk factors.

PMID- 29175342
TI  - A new preparation strategy for surface modified PLA nanoparticles to enhance
      uptake by endothelial cells.
AB  - Nanoparticles are promising drug delivery systems to overcome physiological
      barriers such as the blood-brain barrier. In this respect nanoparticle uptake
      into endothelial or epithelial cells is the first necessary step to overcome
      these obstacles. Therefore, a new strategy for the covalent attachment of drug
      targeting ligands on poly(lactic acid) (PLA) nanoparticles was developed and the
      influence of the resulting surface properties on the uptake behaviour in cerebral
      endothelial cells was investigated. PLA nanoparticles were modified on their
      surface by apolipoprotein E, penetratin, or ovalbumin using a newly developed
      vinyl sulfone-modified poly(vinyl alcohol)-derivative (VS-PVA) as steric
      stabilizer. With this approach an easy option for ligand coupling reactions to
      PVA-stabilized nanoparticles was achieved. All obtained formulations showed a
      favourable behaviour concerning cytotoxic effects on endothelial cells, not
      compromising their viability. Furthermore, a clear relation between cellular
      uptake and surface coupled functional ligand could be determined: Penetratin- and
      apolipoprotein E-modified nanoparticles showed a distinct higher cellular uptake
      than ovalbumin-modified or unmodified nanoparticles, which both can be explained
      by mechanistic reasons. Overall the use of the reactive VS-PVA as stabilizer for
      nanoparticle preparation is an universal and effective approach to couple several
      functional ligands to the particles' surface for targeting applications.

PMID- 29175343
TI  - Diffuse sources of contamination in freshwater fish: Detecting effects through
      active biomonitoring and multi-biomarker approaches.
AB  - Aquatic organisms are usually exposed to a mixture of xenobiotics that may exert
      a large effect even in low concentrations, and when information is obtained
      exclusively from chemical analyses the prediction of the deleterious effects is
      potentially hindered. Therefore, the application of complementary monitoring
      methods is a priority. Here, in addition to chemical analyses, an active
      biomonitoring study using multiple biomarker responses in Nile tilapia
      Oreochromis niloticus was conducted to assess the effects of a contamination
      gradient along four reservoirs in Iguacu River. Chemical analysis in the muscle
      showed high levels of metals in fish from the reservoir closest to an
      industrialized and environmentally degraded area, however fish exposed to all
      studied reservoirs showed hepatic alterations (necrosis and inflammatory
      processes). Also, significant variations of biochemical biomarkers were observed
      with no clear indication of contamination gradient, since an indicative of higher
      impact was found in an intermediary reservoir, including high concentrations of
      biliary polycyclic aromatic hydrocarbons (PAHs). However, nuclear morphological
      alterations (NMA) were less frequent at the same reservoir. Thus, the multi
      biomarker approach allied to active biomonitoring is a practical and important
      tool to assess deleterious effects of contamination in freshwater, providing data
      for monitoring and conservation protocols.

PMID- 29175344
TI  - Inoculation of soil with an Isoproturon degrading microbial community reduced the
      pool of "real non-extractable" Isoproturon residues.
AB  - During pesticides degradation, biogenic non-extractable residues ("apparent NER")
      may not share the same environmental fate and risks with the "real NER" that are
      bound to soil matrix. It is not clear how microbial community (MC) inoculation
      for pesticides degradation would influence the NER composition. To investigate
      degradation efficiency of pesticides Isoproturon (IPU) and NER composition
      following MC inoculation, clay particles harboring MC that contains the IPU
      degrading strain, Sphingomonas sp., were inoculated into soil receiving 14C
      labeled IPU addition. Mineralization of IPU was greatly enhanced with MC
      inoculation that averagely 55.9% of the applied 14C-IPU was consumed up into
      14CO2 during 46 days soil incubation. Isoproturon degradation was more thorough
      with MC than that in the control: much less amount of metabolic products (4.6% of
      applied IPU) and NER (35.4%) formed in MC treatment, while the percentages were
      respectively 30.3% for metabolites and 49.8% for NER in the control. Composition
      of NER shifted with MC inoculation, that relatively larger amount of IPU was
      incorporated into the biogenic "apparent NER" in comparison with "real NER".
      Besides its well-recognized role on enhancing mineralization, MC inoculation with
      clay particles benefits soil pesticides remediation in term of reducing "real
      NER" formation, which has been previously underestimated.

PMID- 29175345
TI  - Quaternary ammonium cationic surfactants increase bioactivity of indoxacarb on
      pests and toxicological risk to Daphnia magna.
AB  - Agricultural researchers have always been pursuing synergistic technique for pest
      control. To evaluate the combined effects of quaternary ammonium compounds (QACs)
      and indoxacarb, their independent and joint toxicities to two insects, Spodoptera
      exigua and Agrotis ipsilon, and the aquatic organism, Daphnia magna, were
      determined. Results showed that all of five tested QACs increased the toxicity of
      indoxacarb to S. exigua and A. ipsilon. Both of benzyldimethyltetradecylammonium
      chloride (TDBAC) and benzododecinium chloride (DDBAC) exhibited significantly
      increased toxicities to S. exigua with synergic ratios of 11.59 and 6.55, while
      that to A. ipsilon were 2.60 and 3.45, respectively. When exposed to binary
      mixtures of QACs and indoxacarb, there was synergism on D. magna when using
      additive index and concentration addition methods, but only TDBAC, STAC and ODDAC
      showed synergistic effect in the equivalent curve method. The results indicate
      that the surfactants can be used as the synergists of indoxacarb in the control
      of Lepidoptera pests. However, their environmental risks should not be neglected
      owing to the high toxicity of all mixtures of indoxacarb and five QACs to D.
      magna.

PMID- 29175346
TI  - Determination of water quality, toxicity and estrogenic activity in a nearshore
      marine environment in Rio de Janeiro, Southeastern Brazil.
AB  - Endocrine disrupting compounds (EDCs) can be found in domestic sewage, wastewater
      treatment plant effluents, natural water, rivers, lakes and in the marine
      environment. Jurujuba Sound, located in the state of Rio de Janeiro, Southeastern
      Brazil, receives untreated sewage into its waters, one the main sources of
      aquatic contamination in this area. In this context, the aim of the present study
      was to evaluate the estrogenic potential of water sampled from different depths
      and from areas with differential contamination levels throughout Jurujuba Sound.
      Water quality was evaluated and acute toxicity assays using Allviibrio fischeri
      were conducted, while estrogenic activity of the water samples was determined by
      a Yeast Estrogen Screening assay (YES). Water quality was mostly within the
      limits established for marine waters by the Brazilian legislation, with only DOC
      and ammoniacal nitrogen levels above the maximum permissible limits. No acute
      toxicity effects were observed in the Allivibrio fisheri assay. The YES assay
      detected moderate estrogenic activity in bottom water samples from 3 sampling
      stations, ranging from 0.5 to 3.2ngL-1, as well as in one surface water sample.
      Estrogenic activity was most frequently observed in samples from the bottom of
      the water column, indicating adsorption of estrogenic compounds to the sediment.

PMID- 29175347
TI  - Adaptation of the white shrimp Litopenaeus vannamei to gradual changes to a low
      pH environment.
AB  - pH variation could cause a stress response in euryhaline penaeids, we evaluated
      the mortality, growth performance, osmoregulation gene expression, digestive
      enzyme activity, histology, and resistance against Vibrio parahemolyticus of
      white shrimp Litopenaeus vannamei reared under conditions of gradual changes to a
      low-pH environment (gradual-low pH, 6.65-8.20) or a high-pH environment (gradual
      high pH, 8.20-9.81) versus a normal pH environment (8.14-8.31) during a 28-d
      experiment. Consequently, under gradual-high pH, the cumulative mortality rate
      (CMR) rose with time until 39.9% on days 28; the weight gain percentage (WGP) and
      length gain percentage (LGP) decreased continuously. However, under gradual-low
      pH, the CMR of shrimp stabilized at 6.67% during 7-28 d; the WGP and LGP
      decreased first and then returned to normal. These results indicated that L.
      vannamei displayed a moderate tolerance to gradual-low pH, compared with gradual
      high pH. Under gradual-low pH, the Na+/K+-ATPase, cytoplasmic carbonic anydrase
      (CAc), and glycosyl-phosphatidylinositol-linked carbonic anhydrase (CAg)
      transcripts of shrimp increased continuously or then back to normal; the amylase,
      lipase, and trypsin activities decreased first and then returned to normal or
      increased; the hepatopancreases and midguts showed histopathological lesions
      first and then got remission. Thus, the major adaptation mechanism of shrimp to
      gradual-low pH might be its high osmoregulation ability, which made shrimp
      achieve a new, balanced steady-state, then promoted longer intestinal villi and
      recuperative hepatopancreases of shrimp with enhanced digestive enzyme activities
      to increase nutrient absorption after long-term exposure. Meanwhile, the enhanced
      resistance against V. parahemolyticus under gradual-low pH would probably inhibit
      disease outbreak in the shrimp farming.

PMID- 29175348
TI  - Safety of methionine, a novel biopesticide, to adult and larval honey bees (Apis
      mellifera L.).
AB  - Methionine is an essential/indispensible amino acid nutrient required by adult
      and larval honey bees (Apis mellifera L. [Hymenoptera: Apidae]). Bees are unable
      to rear broods on pollen deficient in methionine, and reportedly behaviorally
      avoid collecting pollen or nectar from florets deficient in methioinine. In
      contrast, it has been demonstrated that methionine is toxic to certain pest
      insects; thus it has been proposed as an effective biopesticide. As an
      ecofriendly integrated pest management agent, methionine boasts a novel mode of
      action differentiating it from conventional pesticides, while providing non
      target safety. Pesticides that minimize collateral effects on bees are desirable,
      given the economic and ecological concerns about honey bee health. The aim of the
      present study was to assess the potential impact of the biopesticide methionine
      on non-target adult and larval honey bees. Acute contact adult toxicology
      bioassays, oral adult assessments and chronic larval toxicity assessments were
      performed as per U.S. Environmental Protection Agency (EPA) requirements. Our
      results demonstrated that methionine fits the U.S. EPA category of practically
      nontoxic (i.e. lethal dose to 50% mortality or LD50 > 11ug/bee) to adult honey
      bees. The contact LD50 was > 25ug/bee and the oral LD50 was > 100ug/bee.
      Mortality was observed in larval bees that ingested DL-methionine (effective
      concentration to 50% mortality or EC50 560ug/bee). Therefore, we conclude that
      methionine poses little threat to the health of the honey bee, due to unlikely
      exposure at concentrations shown to elicit toxic effects.

PMID- 29175349
TI  - CMI workshop in Shanghai, China.

PMID- 29175350
TI  - Comparison of antipseudomonal beta-lactams for febrile neutropenia empiric
      therapy: authors' response.

PMID- 29175351
TI  - Prevalence, associated factors, outcomes and transmission of extensively drug
      resistant tuberculosis among multidrug-resistant tuberculosis patients in Sao
      Paulo, Brazil: a cross-sectional study.
AB  - OBJECTIVES: To describe the prevalence, associated factors, treatment outcomes
      and transmission of extensively drug-resistant (XDR) tuberculosis (TB) in the
      state of Sao Paulo, Brazil, for 2011 to 2013. METHODS: Drug susceptibility
      testing to first- and second-line drugs was performed by BACTEC MGIT 960 and
      molecular typing, by IS6110 restriction fragment length polymorphism. Clinical,
      epidemiologic and demographic data were obtained from surveillance information
      systems for TB. Patients were divided into three groups: multidrug resistant
      (MDR) TB (resistance to at least isoniazid and rifampicin), pre-XDR-TB (MDR-TB
      resistant to a fluoroquinolone or to at least one of the second-line injectable
      drugs) and XDR-TB (MDR-TB resistant to a fluoroquinolone and to at least one of
      the second-line injectables). RESULTS: Among the 313 MDR-TB patients identified,
      the prevalence of XDR-TB and pre-XDR-TB was 10.2% (n = 32) and 19.2% (n = 60),
      respectively. Compared to MDR-TB patients, XDR-TB patients were more likely to be
      female (odds ratio (OR) = 2.74, 95% confidence interval (CI), 1.29-5.83), have a
      history of TB (OR = 5.16; 95% CI, 1.52-17.51) and present higher death rates (OR=
      3.74; 95% CI 1.70-8.25). XDR-TB transmission was observed in households, between
      neighbours and between a patient and a healthcare worker in a hospital.
      CONCLUSIONS: The prevalence of XDR-TB in the state of Sao Paulo is close to that
      estimated globally. Most of the XDR-TB patients were treated previously for TB
      and presented the lowest successful outcome rates. Because transmission of XDR-TB
      occurred, it is important that timely diagnosis of drug resistance is performed.

PMID- 29175353
TI  - Classification of instability after reverse shoulder arthroplasty guides surgical
      management and outcomes.
AB  - BACKGROUND: Revision of unstable reverse shoulder arthroplasty (RSA) remains a
      significant challenge. The purpose of this study was to determine the reliability
      of a new treatment-guiding classification for instability after RSA, to describe
      the clinical outcomes of patients stabilized operatively, and to identify those
      with higher risk of recurrence. METHODS: All patients undergoing revision for
      instability after RSA were identified at our institution. Demographic, clinical,
      radiographic, and intraoperative data were collected. A classification was
      developed using all identified causes of instability after RSA and allocating
      them to 1 of 3 defined treatment-guiding categories. Eight surgeons reviewed all
      data and applied the classification scheme to each case. Interobserver and
      intraobserver reliability was used to evaluate the classification scheme.
      Preoperative clinical outcomes were compared with final follow-up in stabilized
      shoulders. RESULTS: Forty-three revision cases in 34 patients met the inclusion
      for study. Five patients remained unstable after revision. Persistent instability
      most commonly occurred in persistent deltoid dysfunction and postoperative
      acromial fractures but also in 1 case of soft tissue impingement. Twenty-one
      patients remained stable at minimum 2 years of follow-up and had significant
      improvement of clinical outcome scores and range of motion. Reliability of the
      classification scheme showed substantial and almost perfect interobserver and
      intraobserver agreement among all the participants (kappa = 0.699 and kappa =
      0.851, respectively). DISCUSSION: Instability after RSA can be successfully
      treated with revision surgery using the reliable treatment-guiding classification
      scheme presented herein. However, more understanding is needed for patients with
      greater risk of recurrent instability after revision surgery.

PMID- 29175352
TI  - Behavioral and biochemical sensitivity to low doses of ketamine: Influence of
      estrous cycle in C57BL/6 mice.
AB  - RATIONALE: Low-dose ketamine is a rapid-acting antidepressant, to which female
      rodents are more sensitive as compared to males. However, the mechanism mediating
      this sex difference in ketamine sensitivity remains elusive. OBJECTIVES: We
      sought to determine whether male and female mice differ in their behavioral
      sensitivity to low doses of ketamine, and uncover how ovarian hormones influence
      females' ketamine sensitivity. We also aimed to uncover some of the molecular
      mechanism(s) in mood-related brain regions that mediate sex differences in
      ketamine antidepressant effects. METHODS: Male and female mice (freely-cycling,
      diestrus 1 [D1], proestrus [Pro], or D1 treated with an estrogen receptor (ER)
      alpha, ERbeta, or progesterone receptor (PR) agonist) received ketamine (0, 1.5,
      or 3 mg/kg, intraperitoneally) and were tested in the forced swim test (FST) 30
      min later. Ketamine's influence over synaptic plasticity markers in the
      prefrontal cortex (PFC) and hippocampus (HPC) of males, D1, and Pro females was
      quantified by Western blot 1 h post-treatment. RESULTS: Males, freely cycling
      females, D1 and Pro females exhibited antidepressant-like responses to 3 mg/kg
      ketamine. Pro females were the only group where ketamine exhibited an
      antidepressant effect at 1.5 mg/kg. D1 females treated with an agonist for
      ERalpha or ERbeta exhibited an antidepressant-like response to 1.5 mg/kg
      ketamine. Ketamine (3 mg/kg) increased synaptic plasticity-related proteins in
      the PFC and HPC of males, D1, and Pro females. Yet, Pro females exhibited an
      increase in p-Akt and p-CaMKIIalpha in response to 1.5 and 3 mg/kg ketamine.
      CONCLUSION: Our results indicate that females' enhanced sensitivity to ketamine
      during Pro is likely mediated through estradiol acting on ERalpha and ERbeta,
      leading to greater activation of synaptic plasticity-related kinases within the
      PFC and HPC.

PMID- 29175354
TI  - Interaction of defibrillation waveform with the time to defibrillation or the
      number of defibrillation attempts on survival from out-of-hospital cardiac
      arrest.
AB  - AIM: Early biphasic defibrillation is effective in out-of-hospital cardiac arrest
      (OHCA) cases. In the resuscitation of patients with OHCA, it is not clear how the
      defibrillation waveform interacts with the time to defibrillation to influence
      patient survival. The second, and any subsequent, shocks need to be administered
      by an on-line physician in Japan. Thus, we investigated the interaction between
      the defibrillation waveform and time to or the number of defibrillation on
      resuscitation outcomes. METHODS: This prospective observational study used data
      for all OHCAs that occurred between 2005 and 2014 in Japan. To investigate the
      interaction effect between the defibrillation waveform and the time to
      defibrillation or the number of defibrillations on the return to spontaneous
      circulation (ROSC), 1-month survival, and cerebral performance category (CPC) (1,
      2), we assessed the modifying effects of the defibrillation waveform and the time
      to or the number of defibrillation on additive scale (i.e., the relative
      excessive risk due to interaction, RERI) and multiplicative scale (i.e., ratio of
      odds ratios (ORs)). RESULTS: In total, 71,566 cases met the inclusion criteria.
      For the measure of interaction between the defibrillation waveform and the time
      to defibrillation, ratio of ORs for ROSC was 0.84 (0.75-0.94), implying that the
      effect of time to first defibrillation on ROSC was negatively modified by
      defibrillation waveform. For the interaction between the defibrillation waveform
      and the number of defibrillations, RERI and ratio of ORs for CPC (1, 2) was -0.25
      (-0.47 to -0.06) and 0.79 (0.67-0.93), respectively. It is implied that the
      effect of number of defibrillation on CPC (1, 2) was negatively modified by
      defibrillation waveform. CONCLUSIONS: An increased number of defibrillations was
      associated with a decreased ROSC in the case of biphasic and monophasic
      defibrillation, while an increased number of defibrillations was related to an
      increased 1-month survival rate and CPC (1, 2) only in the case of biphasic
      defibrillation. When two or more defibrillations were performed, a biphasic
      waveform was more effective in terms of long-term survival than a monophasic
      waveform.

PMID- 29175355
TI  - An assessment of ventilation and perfusion markers in out-of-hospital cardiac
      arrest patients receiving mechanical CPR with endotracheal or supraglottic
      airways.
AB  - AIM OF THE STUDY: Mechanical chest compression (MCPR) devices are considered
      equivalent to manual compressions in patient outcomes in out-of-hospital cardiac
      arrest (OHCA). However, recent data suggest possible harm in patients with a
      supraglottic airway device (SGA) during MCPR. The aim of this study was to
      evaluate differences in direct and indirect markers of ventilation and perfusion
      in patients with cardiac arrest receiving MCPR and who had their airway managed
      with an endotracheal tube (ETT) or SGA. METHODS: We retrospectively reviewed
      Emergency Medical Services (EMS) agencies and emergency department (ED) records
      over a two-year period. We included patients with OHCA who underwent MCPR and who
      had an advanced airway placed. The primary outcome was differences in intra
      arrest end-tidal carbon dioxide (etCO2) measurements. Secondary outcomes included
      intra-arrest ventilation rates, rates of prehospital return of spontaneous
      circulation (ROSC), blood pressure upon prehospital ROSC, and 24-h survival.
      RESULTS: Valid data sets were available for 126 patients. Eighty-four (66.7%) had
      an ETT placed, and 42 (33.3%) had a SGA placed. Twenty-eight (22.6%) achieved
      prehospital ROSC. Twenty-four-hour survival data were available for 13 (10.3%) of
      these patients. There were no significant differences in primary or secondary
      outcomes. CONCLUSION: In this retrospective study, we found no evidence of
      differences in markers of ventilation, perfusion or prehospital ROSC and survival
      in patients with OHCA who had their airway managed with either an ETT or SGA
      while receiving MCPR.

PMID- 29175356
TI  - Point-of-care ultrasound use in patients with cardiac arrest is associated
      prolonged cardiopulmonary resuscitation pauses: A prospective cohort study.
AB  - OBJECTIVE: We aim to evaluate if point-of-care ultrasound use in cardiac arrest
      is associated with CPR pause duration. METHODS: This is a prospective cohort
      study of patients with cardiac arrest (CA) presenting to an urban emergency
      department from July 2016 to January 2017. We collected video recordings of
      patients with CA in designated code rooms with video recording equipment. The CAs
      recordings were reviewed and coded by two abstractors. The primary outcome was
      the difference CPR pause duration when POCUS was and was not performed. RESULTS:
      A total of 110 CPR pauses were evaluated during this study. The median CPR pause
      with POCUS performed lasted 17s (IQR 13 - 22.5) versus 11s (IQR 7 - 16) without
      POCUS. In addition, multiple regression analysis demonstrated that POCUS was
      associated with longer pauses (6.4s, 95%CI 2.1- 10.8); ultrasound fellowship
      trained faculty trended towards shorter CPR pauses (-4.1s, 95%CI -8.8-0.6)
      compared to non-ultrasound fellowship trained faculty; and when the same provider
      led the resuscitation and performed the POCUS, pause durations were 6.1s (95%CI
      0.4 -11.8) longer than when another provider performed the POCUS. CONCLUSION: In
      this prospective cohort trial of 24 patients with CA, POCUS during CPR pauses was
      associated with longer interruptions in CPR.

PMID- 29175358
TI  - Variation and correlation of end-tidal CO2 and amplitude spectrum area in a
      refractory ventricular fibrillation. A case from the ReCaPTa study.

PMID- 29175357
TI  - Hemodynamic effects of IV sodium nitrite in hospitalized comatose survivors of
      out of hospital cardiac arrest.
AB  - BACKGROUND: Patients resuscitated from cardiac arrest have brain and cardiac
      injury. Recent animal studies suggest that the administration of sodium nitrite
      after resuscitation from 12min of asystole limits acute cardiac dysfunction and
      improves survival and neurologic outcomes. It has been hypothesized that low
      doses of IV sodium nitrite given during resuscitation of out of hospital cardiac
      arrest (OHCA) will improve survival. Low doses of sodium nitrite (e.g., 9.6mg of
      sodium nitrite) are safe in healthy individuals, however the effect of nitrite on
      blood pressure in resuscitated cardiac arrest patients is unknown. METHODS: We
      performed a single-center, pilot trial of low dose sodium nitrite (1 or 9.6mg
      dose) vs. placebo in hospitalized out-of-hospital cardiac arrest patient to
      determine whether nitrite administration reduced blood pressure and whether whole
      blood nitrite levels increased in response to nitrite administration. RESULTS:
      This is the first reported study of sodium nitrite in cardiac arrest patients.
      Infusion of low doses of sodium nitrite in comatose survivors of OHCA (n=7)
      compared to placebo (n=4) had no significant effects on heart rate within 30min
      after infusion (70+/-20 vs. 78+/-3 beats per minute, p=0.18), systolic blood
      pressure (103+/-20 vs 108+/-15mmHg, p=0.3), or methemoglobin levels (0.92+/-0.33
      vs. 0.70+/-0.26, p=0.45). Serum nitrite levels of 2-4MUM were achieved within
      15min of a 9.6mg nitrite infusion. CONCLUSIONS: Low dose sodium nitrite does not
      cause significant hemodynamic effect in patients with OHCA, which suggests that
      nitrite can be delivered safely in this critically ill patient population. Higher
      doses of sodium nitrite are necessary in order to achieve target serum level of
      10MUM.

PMID- 29175359
TI  - Trial Duration and Risk Reduction in Combination Therapy Trials for Pulmonary
      Arterial Hypertension: A Systematic Review.
AB  - BACKGROUND: Relative risk (RR) and number needed-to-treat (NNT) are frequently
      time-dependant measures. We performed a systematic review and meta-analysis to
      assess whether trial duration influenced the relative and absolute risk of
      worsening in randomized controlled trials (RCTs) comparing combination therapy
      (CT) of pulmonary arterial hypertension (PAH)-specific therapies vs monotherapy
      (MT). METHODS: We searched MEDLINE, Embase, and the Cochrane Library (January
      1990 to September 2016) for RCTs assessing CT compared with MT in PAH. The
      primary outcome was the risk of clinical worsening. We assessed whether trial
      duration correlated with RR and NNT using weighted meta-regression with mixed
      effects. Changes in NNT overtime were also assessed using data from long-term
      event-driven trials. RESULTS: There were 3,801 patients throughout 15 studies
      included. The RR for clinical worsening positively correlated with trial duration
      (R2 = 0.67, P = .0002), whereas the NNT did not (mean NNT, 7; R2 = 0.02; P =
      .65). Among long-term event-driven trials, the mean NNT progressively decreased
      until 52 weeks of follow-up, being stable thereafter. Conversely, the mean RR
      progressively increased from approximately 0.40 at week 16 to approximately 0.68
      at week 104. CONCLUSIONS: Absolute risk reduction of clinical worsening was
      relatively constant beyond 6 to 12 months of treatment in clinical trials
      comparing CT with MT in PAH. These results question the need for CT trials of
      very long duration in PAH.

PMID- 29175360
TI  - Efficacy of Acupuncture Is Noninferior to Nicotine Replacement Therapy for
      Tobacco Cessation: Results of a Prospective, Randomized, Active-Controlled Open
      Label Trial.
AB  - BACKGROUND: We designed and conducted this multicenter randomized active
      controlled open-label trial to evaluate the efficacy of acupuncture, auricular
      point pressing, and nicotine replacement therapy (NRT) on tobacco cessation in
      the Chinese population. METHODS: This randomized controlled trial was conducted
      in seven hospitals in China between October 2013 and February 2016. Eligible
      participants were recruited and randomly assigned to receive acupuncture or
      auricular point pressing or NRT via a central randomization system with a 1:1:1
      ratio. All treatment was given for a total of 8 weeks, and follow-up visit was at
      16 weeks. The primary outcome measure was carbon monoxide (CO)-confirmed 24-h
      point abstinence rate (<10 parts per million), 24 weeks after quit day. RESULTS:
      A total of 300 participants were recruited and 195 participants finished, with a
      dropout rate of 35.00%. Two cases of adverse events in the acupuncture group and
      2 cases in the NRT group were observed. The CO-confirmed 24-h point abstinence
      rate was 43.00% at 24 weeks in the acupuncture group, which was similar to 44.00%
      in the NRT group (P > .05), but significantly higher than the 30.00% in the
      auricular point group (P < .05). At 24 weeks, the Fagerstrom Nicotine Dependence
      Test and the Minnesota Nicotine Withdrawal Scale scores in the acupuncture group
      were significantly lower than those in the auricular point group and in the NRT
      group (P < .05). Kaplan-Meier analysis showed the time to relapse for acupuncture
      (44.12 days) was insignificantly longer than NRT (41.18 days), but significantly
      longer than auricular point pressing (29.53 days). CONCLUSIONS: We found
      acupuncture was safe and a possible treatment for tobacco cessation, but it
      requires further study to establish its role. TRIAL REGISTRY: Chinese Clinical
      Trial Registry; No.: ChiCTR-TRC-13003544; URL:
      http://www.chictr.org.cn/abouten.aspx.

PMID- 29175362
TI  - Systematic review and meta-analyses of useful field of view cognitive training.
AB  - Systematic review and meta-analyses were conducted of Useful Field of View (UFOV)
      training, which was evaluated by Institute of Medicine criteria. Forty-four
      studies of UFOV training from 17 randomized trials conducted among adults were
      identified in systematic review. Results addressing the Institute of Medicine
      criteria indicated that: (a) UFOV training enhanced neural outcomes, speed of
      processing, and attention. (b) UFOV training effects were equivalent when
      compared to active- or no-contact control conditions. (c) UFOV training showed
      far transfer to everyday function. (d) Improvements on the trained skills endured
      across ten years. (e) Half of the clinical trials identified were conducted by
      researchers without financial interests in UFOV training. Results indicated that
      UFOV training effects were larger for adaptive- than non-adaptive training
      techniques, and in community-based as compared to clinical samples. UFOV training
      did not transfer to other neuropsychological outcomes, but positively enhanced
      well-being, health, and quality of life longitudinally. Criticisms of cognitive
      training are addressed. UFOV training should be implemented among older adults to
      improve real-world functional outcomes and well-being.

PMID- 29175361
TI  - The Role of Computed Tomography for the Evaluation of Lung Disease in Alpha-1
      Antitrypsin Deficiency.
AB  - Alpha-1 antitrypsin deficiency (AATD) is characterized by low serum levels of or
      dysfunctional alpha-1 proteinase inhibitor. In the lung parenchyma, this results
      in a loss of protection against the activity of serine proteases, particularly
      neutrophil elastase. The resultant imbalance in protease and antiprotease
      activity leads to an increased risk for the development of early-onset emphysema
      and COPD. As in traditional smoke-related COPD, the assessment of the severity
      and disease progression of lung disease in AATD is conventionally based on lung
      function; however, pulmonary function tests are unable to discriminate between
      emphysema and airways disease, the two hallmark pathologic features of COPD. CT
      imaging has been used as a tool to further characterize lung structure and
      evaluate therapeutic interventions in AATD-related COPD. Moreover, recent
      advances in quantitative CT have significantly improved our assessment of the
      lung architecture, which has provided investigators and clinicians with a more
      detailed evaluation of the extent and severity of emphysema and airways disease
      in AATD. In addition, serial CT imaging measures are becoming increasingly
      important, as they provide a tool to monitor emphysema progression. This review
      describes the principles of CT technology and the role of CT imaging in assessing
      pulmonary disease progression in AATD, including the effect of therapeutic
      interventions.

PMID- 29175364
TI  - Open questions on the 3D structures of collagen containing vertebrate mineralized
      tissues: A perspective.
AB  - Our current understanding of the structures of vertebrate mineralized tissues is
      largely based on light microscopy/histology and projections of 3D structures onto
      2D planes using electron microscopy. We know little about the fine details of
      these structures in 3D at the length scales of their basic building blocks, the
      inherent variations of structure within a tissue and the cell-extracellular
      tissue interfaces. This limits progress in understanding tissue formation,
      relating structure to mechanical and metabolic functions, and obtaining deeper
      insights into pathologies and the evolution of these tissues. In this perspective
      we identify and discuss a series of open questions pertaining to collagen
      containing vertebrate mineralized tissues that can be addressed using appropriate
      3D structural determination methods. By so doing we hope to encourage more
      research into the 3D structures of mineralized vertebrate tissues.

PMID- 29175363
TI  - Bone morphogenetic protein signaling through ACVR1 and BMPR1A negatively
      regulates bone mass along with alterations in bone composition.
AB  - Bone quantity and bone quality are important factors in determining the
      properties and the mechanical functions of bone. This study examined the effects
      of disrupting bone morphogenetic protein (BMP) signaling through BMP receptors on
      bone quantity and bone quality. More specifically, we disrupted two BMP
      receptors, Acvr1 and Bmpr1a, respectively, in Osterix-expressing osteogenic
      progenitor cells in mice. We examined the structural changes to the femora from 3
      month old male and female conditional knockout (cKO) mice using micro-computed
      tomography (micro-CT) and histology, as well as compositional changes to both
      cortical and trabecular compartments of bone using Raman spectroscopy. We found
      that the deletion of Acvr1 and Bmpr1a, respectively, in an osteoblast-specific
      manner resulted in higher bone mass in the trabecular compartment. Disruption of
      Bmpr1a resulted in a more significantly increased bone mass in the trabecular
      compartment. We also found that these cKO mice showed lower mineral-to-matrix
      ratio, while tissue mineral density was lower in the cortical compartment.
      Collagen crosslink ratio was higher in both cortical and trabecular compartments
      of male cKO mice. Our study suggested that BMP signaling in osteoblast mediated
      by BMP receptors, namely ACVR1 and BMPR1A, is critical in regulating bone
      quantity and bone quality.

PMID- 29175365
TI  - Roles of three Fusarium graminearum membrane Ca2+ channels in the formation of
      Ca2+ signatures, growth, development, pathogenicity and mycotoxin production.
AB  - Similar to animals and plants, external stimuli cause dynamic spatial and
      temporal changes of cytoplasmic Ca2+ in fungi. Such changes are referred as the
      Ca2+ signature and control cellular responses by modulating the activity or
      location of diverse Ca2+-binding proteins (CBPs) and also indirectly affecting
      proteins that interact with CBPs. To understand the mechanism underpinning Ca2+
      signaling, therefore, characterization of how Ca2+ moves to and from the
      cytoplasm to create Ca2+ signatures under different conditions is fundamental.
      Three genes encoding plasma membrane Ca2+ channels in a Fusarium graminearum
      strain that expresses a fluorescent protein-based Ca2+ indicator in the cytoplasm
      were mutagenized to investigate their roles in the generation of Ca2+ signatures
      under different growth conditions and genetic backgrounds. The genes disrupted
      include CCH1 and MID1, which encode a high affinity Ca2+ uptake system, and FIG1,
      encoding a low affinity Ca2+ channel. Resulting mutants were also analyzed for
      growth, development, pathogenicity and mycotoxin production to determine how loss
      of each of the genes alters these traits. To investigate whether individual genes
      influence the function and expression of other genes, phenotypes and Ca2+
      signatures of their double and triple mutants, as well as their expression
      patterns, were analyzed.

PMID- 29175366
TI  - Lack of the NAD+-dependent glycerol 3-phosphate dehydrogenase impairs the
      function of transcription factors Sip4 and Cat8 required for ethanol utilization
      in Kluyveromyces lactis.
AB  - The NAD+-dependent glycerol 3-phosphate dehydrogenase (KlGpd1) is an important
      enzyme for maintenance of the cytosolic redox balance in the milk yeast
      Kluyveromyces lactis. The enzyme is localized in peroxisomes and in the cytosol,
      indicating its requirement for the oxidation of NADH in both compartments. Klgpd1
      mutants grow more slowly on glucose than wild-type cells and do not grow on
      ethanol as a sole carbon source. We studied the molecular basis of the latter
      phenotype and found that Gpd1 is required for high expression of KlICL1 and
      KlMLS1 which encode the key enzymes of the glyoxylate pathway isocitrate lyase
      and malate synthase, respectively. This regulation is mediated by CSRE elements
      in the promoters of these genes and the Snf1-regulated transcription factors
      KlCat8 and KlSip4. To study the transactivation function of these factors we
      developed a modified yeast one-hybrid system for K. lactis, using the endogenous
      beta-galactosidase gene LAC4 as a reporter in a lac9 deletion background. In
      combination with ChIP analyses we discovered that Gpd1 controls both the specific
      binding of Cat8 and Sip4 to the target promoters and the capacity of these
      factors to activate the reporter gene expression. We propose a model in which
      KlGpd1 activity is required for maintenance of the redox balance. In its absence,
      genes which function in generating redox balance instabilities are not expressed.
      A comparison of mutant phenotypes further indicates, that this system not only
      operates in K. lactis, but also in Saccharomyces cerevisiae.

PMID- 29175367
TI  - Spatial heterogeneity of glycogen and its metabolizing enzymes in Aspergillus
      nidulans hyphal tip cells.
AB  - Glycogen is a homopolymer of glucose and a ubiquitous cellular-storage carbon.
      This study investigated which Aspergillus nidulans genes are involved in glycogen
      metabolism. Gene disruptants of predicted glycogen synthase (gsyA) and glycogenin
      (glgA) genes accumulated less cellular glycogen than the wild type strain,
      indicating that GsyA and GlgA synthesize glycogen similarly to other eukaryotes.
      Meanwhile, gene disruption of gphA encoding glycogen phosphorylase increased the
      amount of glycogen to a higher degree than wild type during the stationary phase
      that accompanies carbon-source limitation. GFP-tagged GsyA and GphA were
      distributed in the cytosol and formed punctate and filamentous structures,
      respectively. Carbon starvation resulted in elongated GphA-GFP filaments and
      increased numbers of filaments. These structures were more frequently located in
      the basal regions of tip cells and adjacent cells than in the apical regions of
      tip cells. Cellular glycogen visualized by incorporation of a fluorescent glucose
      analog accumulated in cytoplasmic puncta that were more prevalent in the basal
      regions, a pattern similar to that seen for GsyA. The colocalization of glycogen
      and GsyA at punctate structures in tip and sub-apical cells likely represents the
      cellular machinery for synthesizing glycogen. More frequent colocalization in the
      basal, rather than tip cell apical regions indicated that tip cells have
      differentiated subcellular regions for glycogen synthesis. Our findings regarding
      glycogen, GsyA and GphA distribution evoke the spatial heterogeneity of glycogen
      metabolism in fungal hyphae.

PMID- 29175368
TI  - Active Surveillance in Small Renal Masses in the Elderly: A Literature Review.
AB  - CONTEXT: Small renal masses have become increasingly common due to widespread
      imaging; however, optimal management of these lesions in the elderly can be
      complex due to the competing risks of intervention, natural history of disease,
      patient comorbidities, and expectations. In the properly selected elderly
      patient, active surveillance remains an accepted and attractive treatment
      approach. OBJECTIVE: We completed a literature review of small renal masses
      (enhancing, <4cm, T1aN0M0 disease) in the elderly, aged >=70 yr, aimed at
      identifying the utility of active surveillance in this population. The primary
      outcomes were conversion to active treatment while on active surveillance and
      cancer-specific mortality. Secondary outcomes included predictors of treatment,
      type of treatment performed (partial nephrectomy, radical nephrectomy, and
      ablation), progression to metastases, all-cause mortality, tumor growth rate, and
      demographic data including age and Charlson Comorbidity Index. EVIDENCE
      ACQUISITION: A comprehensive search of electronic databases (e.g., MEDLINE,
      EMBASE, SCOPUS, Web of Science, and the Cochrane Library) using search terms
      "small renal mass" OR "SRM", AND "elderly," "senior," "aging," "geriatric," OR
      "octogenarian" was completed. All randomized controlled trials, nonrandomized
      comparison studies, and case series were included and screened by the reviewers.
      All comparison studies included in the systematic review were assessed for
      methodological quality using the Cochrane Risk of Bias tools. EVIDENCE SYNTHESIS:
      Seventeen primary studies including 36495 patients met the inclusion criteria for
      the systematic review. All studies were retrospective institutional chart or the
      Surveillance, Epidemiology, and End Results database reviews. There was a low (4
      26%) rate of conversion to active treatment for active surveillance in the
      identified studies over a follow-up interval of up to 91.5 mo. Overall mortality
      was substantial in this elderly cohort, with 15-51% of patients being deceased
      over the course of study follow-up; however, there was minimal cancer-specific
      mortality due to patients succumbing to alternative comorbid disease. In the
      future, patient comorbidity and biological age versus the natural history of the
      individualized tumor biology may play an increasing role in the discussion
      regarding treatment options and consideration of active surveillance.
      CONCLUSIONS: Active surveillance is an effective management strategy in the
      elderly population. Few patients required the conversion to active treatment and
      there was low cancer-specific mortality. The majority of patients who expired
      over the course of the identified studies succumbed to alternative disease. The
      goal of treatment strategies should include weighing patient-specific prognosis
      relative to their competing health risks and treatment goals against the natural
      history of disease and risks of intervention. PATIENT SUMMARY: In this review
      article, the authors examined the utility of active surveillance in the setting
      of a small localized renal mass in the elderly population. Despite being on
      surveillance, we found that cancer-specific outcomes were excellent, and overall
      mortality was often a result of comorbid disease. However, there is significant
      heterogeneity among elderly patients, and treatment approaches should be focused
      around patient-centered goals and prognosis.

PMID- 29175369
TI  - Serum IgE as an immunological marker to predict response to omalizumab treatment
      in symptomatic chronic urticaria.

PMID- 29175370
TI  - Atopy Is Associated with Age at Asthma Onset in Elderly Patients.
AB  - BACKGROUND: Asthma in the elderly population (60 years of age and older) is
      frequently underdiagnosed, as well as atopy. Atopy, although more prevalent in
      younger patients, can be a major cause of asthma in the elderly. Chronic
      obstructive pulmonary disease (COPD) and cardiovascular disease are common
      differential diagnoses, especially in elderly smokers. OBJECTIVE: The objective
      of this study was to assess atopy and comorbidities in elderly patients with
      asthma. METHODS: This was an observational and retrospective study involving
      elderly asthmatic patients followed up at a tertiary center. Patients were
      assessed for severity of asthma, frequency of atopy, and frequency of
      comorbidities concomitant with asthma. Then, they were classified according to
      their age at asthma onset and the groups compared with each other for atopy,
      spirometric parameters, and comorbidities. RESULTS: This study included 243
      elderly asthmatic patients, 71.8% of them presenting severe disease and 82.3%
      forced expiratory volume in 1 second (FEV1) < 80%. Gastroesophageal reflux
      disease, obesity, and asthma-COPD overlap syndrome were observed, respectively,
      in 64%, 37%, and 13% of these patients. Atopy was observed in 63%, mainly in
      those with early onset disease, and its frequency decreased as the age of asthma
      onset increased (P < .05). Total serum IgE was higher for allergic patients and
      FEV1 values were lower for patients with long-term asthma. Aspirin-exacerbated
      respiratory disease was more frequent in patients with nonallergic asthma.
      CONCLUSIONS: Most elderly asthmatic patients followed up in our tertiary center
      were atopic and higher values of total serum IgE suggest atopy. Atopy was
      inversely correlated with age of asthma onset. The diagnosis of allergic asthma
      in the elderly population is essential to treat patients more properly, improving
      their quality of life and decreasing asthma morbidity and mortality.

PMID- 29175371
TI  - Natural History of Benign Nonimmediate Allergy to Beta-Lactams in Children: A
      Prospective Study in Retreated Patients After a Positive and a Negative
      Provocation Test.
AB  - BACKGROUND: The drug provocation test (DPT) is considered as the gold standard to
      diagnose drug allergy and is particularly important in the diagnosis of
      nonimmediate beta-lactam (BL) allergy in children. The natural history of BL
      allergy remains unknown. OBJECTIVE: Our main aim was to evaluate the natural
      history of nonimmediate BL hypersensitivity and the long-term tolerance
      acquisition, and our secondary objective was to determine the negative predictive
      value (NPV) of the DPT following a 2-day protocol. METHODS: Children developing a
      benign rash while treated by BL were prospectively recruited at the Emergency
      Department of the Geneva University Hospital from 2006 to 2011 and challenged
      with the incriminated BL (initial diagnostic drug provocation test [idDPT])
      following a 2-day protocol. In case of a positive idDPT, the patients underwent a
      follow-up drug provocation test (fuDPT) 3 years later. In case of a negative
      idDPT, we sent a questionnaire to assess tolerance of a subsequent treatment with
      the incriminated BL. RESULTS: Among the 18 children with a positive idDPT, 16
      children (89%) had a negative fuDPT and 2 children developed a benign exanthema.
      Among those 16 children, 11 tolerated a subsequent treatment with the
      incriminated BL without any reaction, suggesting natural antibiotic tolerance
      acquisition. From another point of view, we found that the NPV of the DPT
      following a 2-day protocol was excellent at 96.7%. CONCLUSIONS: Our data strongly
      suggest that a fuDPT is safe and useful to assess tolerance acquisition in
      children with a confirmed benign nonimmediate BL allergy. In addition, our
      results support the use of a short DPT protocol (2 days), which led to a high NPV
      of 96.7% in our population, with a favorable benefit-risk balance.

PMID- 29175373
TI  - Non-invasive T1rho mapping of the human cartilage response to loading and
      unloading.
AB  - OBJECTIVE: To define the physiological response to sequential loading and
      unloading in histologically intact human articular cartilage using serial T1rho
      mapping, as T1rho is considered to indicate the tissue's macromolecular content.
      METHOD: 18 macroscopically intact cartilage-bone samples were obtained from the
      central lateral femoral condyles of 18 patients undergoing total knee
      replacement. Serial T1rho mapping was performed on a clinical 3.0-T MRI system
      using a modified prostate coil. Spin-lock multiple gradient-echo sequences prior
      to, during and after standardized indentation loading (displacement controlled,
      strain 20%) were used to obtain seven serial T1rho maps: unloaded (delta0), quasi
      statically loaded (indentation1-indentation3) and under subsequent relaxation
      (relaxation1-relaxation3). After manual segmentation, zonal and regional regions
      of-interest were defined. ROI-specific relative changes were calculated and
      statistically assessed using paired t-tests. Histological (Mankin classification)
      and biomechanical (unconfined compression) evaluations served as references.
      RESULTS: All samples were histologically and biomechanically grossly intact
      (Mankin sum: 1.8 +/- 1.2; Young's Modulus: 0.7 +/- 0.4 MPa). Upon loading, T1rho
      consistently increased throughout the entire sample thickness, primarily
      subpistonally (indentation1 [M +/- SD]: 9.5 +/- 7.8% [sub-pistonal area, SPA] vs
      4.2 +/- 5.8% [peri-pistonal area, PPA]; P < 0.001). T1rho further increased with
      ongoing loading (indentation3: 14.1 +/- 8.1 [SPA] vs 7.7 +/- 5.9% [PPA]; P <
      0.001). Even upon unloading (i.e., relaxation), T1rho persistently increased in
      time. CONCLUSION: Serial T1rho-mapping reveals distinct and complex zonal and
      regional changes in articular cartilage as a function of loading and unloading.
      Thereby, longitudinal adaptive processes in hyaline cartilage become evident,
      which may be used for the tissue's non-invasive functional characterization by
      T1rho.

PMID- 29175372
TI  - NAD-biosynthetic enzyme NMNAT1 reduces early behavioral impairment in the htau
      mouse model of tauopathy.
AB  - NAD metabolism and the NAD biosynthetic enzymes nicotinamide nucleotide
      adenylyltransferases (NMNATs) are thought to play a key neuroprotective role in
      tauopathies, including Alzheimer's disease. Here, we investigated whether
      modulating the expression of the NMNAT nuclear isoform NMNAT1, which is important
      for neuronal maintenance, influences the development of behavioral and
      neuropathological abnormalities in htau mice, which express non-mutant human tau
      isoforms and represent a model of tauopathy relevant to Alzheimer's disease.
      Prior to the development of cognitive symptoms, htau mice exhibit tau
      hyperphosphorylation associated with a selective deficit in food burrowing, a
      behavior reminiscent to activities of daily living which are impaired early in
      Alzheimer's disease. We crossed htau mice with Nmnat1 transgenic and knockout
      mice and tested the resulting offspring until the age of 6 months. We show that
      overexpression of NMNAT1 ameliorates the early deficit in food burrowing
      characteristic of htau mice. At 6 months of age, htau mice did not show
      neurodegenerative changes in both the cortex and hippocampus, and these were not
      induced by downregulating NMNAT1 levels. Modulating NMNAT1 levels produced a
      corresponding effect on NMNAT enzymatic activity but did not alter NAD levels in
      htau mice. Although changes in local NAD levels and subsequent modulation of NAD
      dependent enzymes cannot be ruled out, this suggests that the effects seen on
      behavior may be due to changes in tau phosphorylation. Our results suggest that
      increasing NMNAT1 levels can slow the progression of symptoms and
      neuropathological features of tauopathy, but the underlying mechanisms remain to
      be established.

PMID- 29175374
TI  - Social capital and preventive care use among the elderly under Taiwan's National
      Health Insurance.
AB  - OBJECTIVE: The National Health Insurance (NHI) system in Taiwan provides free
      annual preventive care services and other disease-specific preventive care
      services under low copayments to people aged 65 and older, yet their utilization
      rates remain low ever since implementation. This study investigates whether
      social capital is associated with preventive care use among people aged 65 and
      older. METHOD: Using the 2009 National Health Interview Study, this study
      measures social capital by the elderly's social network and social participation,
      and employs the logistic regressions to estimate the association between social
      capital and the odds of using a variety of preventive care services. RESULTS: The
      results show that social capital in terms of social network and social
      participation is significantly associated with the use of NHI general preventive
      care services. For disease-specific preventive care, it is social participation,
      rather than social network, that is related to the utilization rate. CONCLUSION:
      The associations between social capital and different types of preventive care
      use found in our study could be considered as an important factor when making
      policies to promote the utilization of preventive care.

PMID- 29175375
TI  - Posttraumatic growth among people with serious mental illness, psychosis and
      posttraumatic stress symptoms.
AB  - Recent research has shown high rates of exposure to trauma among people with
      serious mental illness (SMI). In addition, studies suggest that psychosis and
      mental illness-related experiences can be extremely traumatic. While some
      individuals develop posttraumatic symptomatology related to these experiences,
      some appear to experience posttraumatic growth (PTG). Little is known, however,
      about PTG as a possible outcome among people who experienced psychosis as well as
      posttraumatic stress symptoms (PTSS). For further understanding of the
      relationship between PTSS and PTG among people with SMI who experienced
      psychosis, 121 participants were recruited from community mental health
      rehabilitation centers and administered trauma and psychiatric questionnaires.
      Results revealed that while high levels of traumatic exposure were common, most
      participants experienced some level of PTG which was contingent upon meaning
      making and coping self-efficacy. In addition, posttraumatic avoidance symptoms
      were found to be a major obstacle to PTG. The range of effect sizes for
      significant results ranged from eta2=0.037 to eta2=0.144. These findings provide
      preliminary evidence for the potential role of meaning making and coping self
      efficacy as mediators of PTG in clinical, highly traumatized populations of
      people with SMI and psychosis. Implications of these findings for future research
      and clinical practice are discussed.

PMID- 29175376
TI  - Control of nuclear beta-dystroglycan content is crucial for the maintenance of
      nuclear envelope integrity and function.
AB  - beta-Dystroglycan (beta-DG) is a plasma membrane protein that has ability to
      target to the nuclear envelope (NE) to maintain nuclear architecture.
      Nevertheless, mechanisms controlling beta-DG nuclear localization and the
      physiological consequences of a failure of trafficking are largely unknown. We
      show that beta-DG has a nuclear export pathway in myoblasts that depends on the
      recognition of a nuclear export signal located in its transmembrane domain, by
      CRM1. Remarkably, NES mutations forced beta-DG nuclear accumulation resulting in
      mislocalization and decreased levels of emerin and lamin B1 and disruption of
      various nuclear processes in which emerin (centrosome-nucleus linkage and beta
      catenin transcriptional activity) and lamin B1 (cell cycle progression and
      nucleoli structure) are critically involved. In addition to nuclear export, the
      lifespan of nuclear beta-DG is restricted by its nuclear proteasomal degradation.
      Collectively our data show that control of nuclear beta-DG content by the
      combination of CRM1 nuclear export and nuclear proteasome pathways is
      physiologically relevant to preserve proper NE structure and activity.

PMID- 29175377
TI  - Soft drug-resistant ovarian cancer cells migrate via two distinct mechanisms
      utilizing myosin II-based contractility.
AB  - The failure of chemotherapeutic drugs in treatment of various cancers is
      attributed to the acquisition of drug resistance. However, the migration
      mechanisms of drug-resistant cancer cells remain incompletely understood. Here we
      address this question from a biophysical perspective by mapping the phenotypic
      alterations in ovarian cancer cells (OCCs) resistant to cisplatin and paclitaxel.
      We show that cisplatin-resistant (CisR), paclitaxel-resistant (PacR) and dual
      drug-resistant (i.e., resistant to both drugs) OCCs are more contractile and
      softer than drug-sensitive cells. Protease inhibition suppresses invasion of CisR
      cells but not of PacR cells, indicative of a protease-dependent mode of migration
      in CisR cells and a protease-independent mode of migration in PacR. Despite these
      differences, actomyosin contractility, mediated by the RhoA-ROCK2-Myosin II
      signaling pathway, regulates both modes of migration. Confined migration
      experiments establish the role of myosin IIA and IIB in mediating nuclear
      translocation and regulation of proteolytic activity. Collectively, our results
      highlight the importance of myosin II as a potential therapeutic target for
      treatment of drug-resistant ovarian cancer cells.

PMID- 29175378
TI  - Increased activity of both CDK1 and CDK2 is necessary for the combinatorial
      activity of WEE1 inhibition and cytarabine.
AB  - Inhibition of WEE1 is emerging as a promising chemosensitization strategy in many
      cancers including acute leukemia. Our lab and others have demonstrated that a
      small-molecule inhibitor of WEE1, AZD1775, sensitizes acute leukemia cells to
      cytarabine; however, a mechanism of combinatorial activity has remained elusive.
      Thus, we sought to determine the relative contribution of WEE1 targets CDK1 and
      CDK2 to the combinatorial activity of AZD1775 and cytarabine. To accomplish this,
      we expressed "WEE1 resistant" CDK1 (CDK1-AF) and CDK2 (CDK2-AF) constructs in a T
      ALL cell line. Expression of CDK1/2-AF together, but neither alone, enhanced the
      anti-proliferative effects, DNA damage and apoptosis induced by cytarabine.
      Furthermore, pharmacologic inhibition of CDK1 alone or CDK1 and CDK2 together
      reduced the combinatorial activity of AZD1775 and cytarabine. Thus, increased
      activity of both CDK1 and CDK2 in response to WEE1 inhibition is necessary for
      the combinatorial activity of AZD1775 and cytarabine. This suggests the role of
      WEE1 in cells with accumulated DNA damage extends beyond regulation of CDK1 and
      the G2/M checkpoint and highlights the importance of WEE1 in mediating
      progression through the cell cycle.

PMID- 29175380
TI  - Anodal transcranial direct current stimulation over left inferior frontal gyrus
      enhances sentence comprehension.
AB  - We tested the possibility of enhancing natural language comprehension through the
      application of anodal tDCS (a-tDCS) over the left inferior frontal gyrus, a key
      region for verbal short-term memory and language comprehension. We designed a
      between subjects sham- and task-controlled study. During tDCS stimulation,
      participants performed a sentence to picture matching task in which targets were
      sentences with different load on short-term memory. Regardless of load on short
      term memory, the Anodal group performed significantly better than the Sham group,
      thus providing evidence that a-tDCS over LIFG enhances natural language
      comprehension. To our knowledge, we apply for the first time tDCS to boost
      sentence comprehension. This result is of special interest also from a clinical
      perspective: applying a-tDCS in patients manifesting problems at the sentence
      level due to brain damage could enhance the effects of behavioral rehabilitation
      procedures aimed to improve language comprehension.

PMID- 29175379
TI  - Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid
      leukemia: A pilot study.
AB  - A precision medicine approach is appealing for use in AML due to ease of access
      to tumor samples and the significant variability in the patients' response to
      treatment. Attempts to establish a precision medicine platform for AML, however,
      have been unsuccessful, at least in part due to the use of small compound panels
      and having relatively slow turn over rates, which restricts the scope of
      treatment and delays its onset. For this pilot study, we evaluated a cohort of 12
      patients with refractory AML using an ex vivo drug sensitivity testing (DST)
      platform. Purified AML blasts were screened with a panel of 215 FDA-approved
      compounds and treatment response was evaluated after 72h of exposure. Drug
      sensitivity scoring was reported to the treating physician, and patients were
      then treated with either DST- or non-DST guided therapy. We observed survival
      benefit of DST-guided therapy as compared to the survival of patients treated
      according to physician recommendation. Three out of four DST-treated patients
      displayed treatment response, while all of the non-DST-guided patients progressed
      during treatment. DST rapidly and effectively provides personalized treatment
      recommendations for patients with refractory AML.

PMID- 29175381
TI  - 20-Hydroxyecdysone promotes release of GBP-binding protein from oenocytoids to
      suppress hemocytic encapsulation.
AB  - Growth-blocking peptide (GBP) is an insect cytokine that stimulates plasmatocyte
      adhesion, thereby playing a critical role in encapsulation reaction. It has been
      previously demonstrated that GBP-binding protein (GBPB) is released upon
      oenocytoid lysis in response to GBP and is responsible for subsequent clearance
      of GBP from hemolymph. However, current knowledge about GBPB is limited and the
      mechanism by which insects increase GBPB levels to inactivate GBP remains largely
      unexplored. Here, we have identified one GBP precursor (HaGBP precursor) gene and
      two GBPB (namely HaGBPB1 and HaGBPB2) genes from the cotton bollworm, Helicoverpa
      armigera. The HaGBP precursor was found to be predominantly expressed in fat
      body, whereas HaGBPB1 and HaGBPB2 were mainly expressed in hemocytes.
      Immunological analyses indicated that both HaGBPB1 and HaGBPB2 are released from
      hemocytes into the plasma during the wandering stage. Additionally, 20
      hydroxyecdysone (20E) treatment or bead challenge could promote the release of
      HaGBPB1 and HaGBPB2 at least partly from oenocytoids into the plasma.
      Furthermore, we demonstrate that the N-terminus of HaGBPB1 is responsible for
      binding to HaGBP and suppresses HaGBP-induced plasmatocyte spreading and
      encapsulation. Overall, this study helps to enrich our understanding of the
      molecular mechanism underlying 20E mediated regulation of plasmatocyte adhesion
      and encapsulation via GBP-GBPB interaction.

PMID- 29175382
TI  - The Influence of Social Threat on Pain, Aggression, and Empathy in Women.
AB  - : Only one published study has investigated the effect of a threatening social
      context on the perception and expression of pain, showing that social threat
      leads to increased pain reports but reduced nonverbal pain expression. The
      current study aimed to replicate and extend these findings to further explore the
      effects of a threatening social context. Healthy, female participants (N = 71)
      received 10 electrocutaneous stimuli delivered by a confederate. They were led to
      believe that the confederate was requested to administer 10 painful stimuli
      (control group) or that the confederate deliberately chose to deliver 10 painful
      stimuli when given the choice to deliver between 1 to 10 painful stimuli (social
      threat group). Self-reported pain intensity, unpleasantness, threat value of
      pain, and painful facial expression were assessed. Additionally, empathy and
      aggression toward the confederate were investigated. Social threat did not affect
      painful facial expression or self-reported pain intensity, but led to increased
      aggression toward the confederate. Moreover, perceived social threat predicted
      the threat value of pain and reduced empathy toward the confederate. We were not
      able to replicate the previously reported dissociation between pain reports and
      pain expression as a result of social threat. However, social threat was
      associated with an increased threat value of pain, increased aggression, and
      reduced empathy. PERSPECTIVE: A threatening social context affects how
      threatening pain is perceived and has interpersonal consequences such as
      increased aggression and reduced empathy, thereby creating a double burden on the
      individual suffering from pain.

PMID- 29175383
TI  - An efficient algorithm for dynamic MRI using low-rank and total variation
      regularizations.
AB  - In this paper, we propose an efficient algorithm for dynamic magnetic resonance
      (MR) image reconstruction. With the total variation (TV) and the nuclear norm
      (NN) regularization, the TVNNR model can utilize both spatial and temporal
      redundancy in dynamic MR images. Such prior knowledge can help model dynamic MRI
      data significantly better than a low-rank or a sparse model alone. However, it is
      very challenging to efficiently minimize the energy function due to the non
      smoothness and non-separability of both TV and NN terms. To address this issue,
      we propose an efficient algorithm by solving a primal-dual form of the original
      problem. We theoretically prove that the proposed algorithm achieves a
      convergence rate of O(1/N) for N iterations. In comparison with state-of-the-art
      methods, extensive experiments on single-coil and multi-coil dynamic MR data
      demonstrate the superior performance of the proposed method in terms of both
      reconstruction accuracy and time complexity.

PMID- 29175384
TI  - Neuron-specific enolase and S-100b in prolonged targeted temperature management
      after cardiac arrest: A randomised study.
AB  - BACKGROUND: We aimed to investigate the impact of prolonged targeted temperature
      management (TTM) in cardiac arrest patients on release of serum levels of NSE and
      S-100b and their prognostic performances. METHODS: This is a substudy of the
      Targeted Temperature Management for 24 vs 48h trial. NSE and S-100b levels were
      analysed retrospectively in serum samples collected upon admission, at 24, 48,
      and 72h after reaching the target temperature of 33+/-1 degrees C. The primary
      outcome was biomarker serum concentrations and secondary outcome was the cerebral
      performance category score after 6 months. RESULTS: 115 patients from two centres
      were analysed. NSE and S-100b levels did not differ between TTM groups at any
      single time-point. Poor outcome patients had higher biomarker levels at 24, 48,
      and 72h: NSE: 9.73 (7.2; 10.9) versus 20.40 (12.7; 27.2), 8.86 (6.6; 9.6) versus
      17.47 (11.1; 37.3) and 6.23 (5.3; 8.5) versus 31.05 (12.8; 52.5) respectively and
      S-100b: 0.09 (0.07; 0.11) versus 0.23 (0.19; 0.39), 0.08 (0.07; 0.09) versus 0.18
      (0.15; 0.33) and 0.07 (0.06; 0.08) versus 0.13 (0.09; 0.23). The daily changes in
      NSE from admission to Day 2 after the cardiac arrest (CA) were also related to
      the outcome (p=0.003 and p=0.02). The best prediction of outcome was found at 72h
      for NSE and at 24h as well as 48h for S100b. CONCLUSIONS: No clinically relevant
      differences were found in the levels of NSE or S-100b between standard and
      prolonged TTM. Prognostic reliability of NSE and S-100b was unaltered by
      prolonged TTM.

PMID- 29175385
TI  - Timing of coronary angiography in survivors of out-of-hospital cardiac arrest
      without obvious extracardiac causes.
AB  - BACKGROUND: Indications and timing of coronary angiography in patients surviving
      out-of-hospital cardiac arrest (OHCA) remain controversial. The aim of the
      present study was to assess the impact of an early invasive strategy in patients
      presenting with an OHCA and no obvious extracardiac cause. METHODS: Between
      January 1st 2009 and December 31st 2014 a total 612 survivors of OHCA were
      admitted to our institution. Patients with no obvious extracardiac cause (n=507)
      were stratified into two groups: patients that underwent cardiac catheterization
      <=3h (early invasive; n=291) and patients not undergoing cardiac catheterization
      within 3h (non-early invasive; n=216). Primary endpoint was all-cause mortality
      at 30days. RESULTS: All-cause 30-day mortality was 28.9% in the early invasive
      group vs. 36.6% in the non-early invasive group (log-rank p=0.071). After
      propensity analyses, an early invasive strategy, as compared to a non-early
      strategy, was not associated with 30-day mortality (adjusted Hazard ratio [HR]
      0.69; 95% CI 0.35-1.37; p=0.029). Cox multivariable regression analyses
      demonstrated age (HR 1.04/year; 95% CI 1.02-1.07) and presentation with
      cardiogenic shock (HR 5.1; 95% CI 1.8-14.0) to be the sole independent predictors
      of 30-day mortality. CONCLUSIONS: In this retrospective study, early coronary
      angiography (<3h), as compared to a non-early invasive strategy, was not
      associated with reduced 30-day mortality in patients hospitalized after OHCA,
      irrespective of the presence of ST segment elevation or cardiogenic shock at
      presentation.

PMID- 29175386
TI  - Impact of Clinicopathologic Features on the Efficacy of PD-1/PD-L1 Inhibitors in
      Patients With Previously Treated Non-small-cell Lung Cancer.
AB  - BACKGROUND: The current study aimed to comprehensively investigate the impact of
      various clinicopathologic features on the efficacy of programmed cell death-1 (PD
      1) and ligand (PD-L1) inhibitors in patients with previously treated non-small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Randomized controlled trials that
      compared PD-1/PD-L1-inhibitor monotherapy with chemotherapy or placebo in
      patients with previously treated NSCLC were included. RESULTS: Five trials were
      included (n = 3025). For all studies, PD-1/PD-L1 inhibitors significantly
      prolonged overall survival (OS) (hazard ratio [HR], 0.70; P < .001) and
      progression-free survival (PFS) versus chemotherapy (HR, 0.86; P = .020).
      Subgroup analysis showed that anti-PD-1/PD-L1 monotherapy could markedly improve
      OS in elderly patients (HR, 0.69; P < .001), female patients (HR, 0.70; P <
      .001), never-smoking patients (HR, 0.73; P = .001), and patients with a histology
      of squamous cell carcinoma (HR, 0.67; P < .001), but not PFS in the elderly and
      female patient groups. Notably, PD-1/PD-L1 inhibitors cannot prolong both OS (HR,
      0.76; P = .390) and PFS (HR, 0.74; P = .210) in patients with central nervous
      system (CNS) metastasis, whereas patients without CNS metastasis could benefit
      from anti-PD-1/PD-L1 monotherapy on OS (HR, 0.71; P < .001). CONCLUSION: PD-1/PD
      L1-inhibitor monotherapy could significantly prolong both OS and PFS in patients
      with previously treated NSCLC. Subgroup analyses showed that most patients
      including elderly, females, never-smokers, and patients with squamous cell
      carcinomas do benefit. However, whether patients with CNS metastasis could
      benefit from anti-PD-1/PD-L1 monotherapy requires further validation.

PMID- 29175387
TI  - Baicalein inhibits cervical cancer progression via downregulating long noncoding
      RNA BDLNR and its downstream PI3K/Akt pathway.
AB  - Baicalein, an active flavonoid extracted from the root of Scutellaria baicalensis
      Georgi, has fascinating anti-cancer effects on many cancers. Our previous study
      also found that baicalein inhibited cervical cancer cell proliferation and
      migration, and induced cervical cancer cell apoptosis and cell cycle arrest.
      However, the molecular mechanisms underlying the anti-cancer effects of baicalein
      are largely unknown. In this study, we identified a novel long noncoding RNA
      (lncRNA), which is downregulated by baicalein in a dose- and time-dependent
      manner in cervical cancer. We named this lncRNA as baicalein down-regulated long
      noncoding RNA (BDLNR). Gain-of- and loss-of-function assays showed that BDLNR was
      required for baicalein-induced cell proliferation inhibition, cell death
      induction, migration inhibition, and in vivo tumor growth inhibition of cervical
      cancer. Mechanistically, BDLNR physically bound to YBX1, recruited YBX1 to PIK3CA
      promoter, activated PIK3CA expression and PI3K/Akt pathway. Furthermore, BDLNR
      was upregulated in cervical cancer and associated with poor prognosis of cervical
      cancer patients. Collectively, our data demonstrated that BDLNR mediated the anti
      cancer effects of baicalein in cervical cancer via activating PI3K/Akt pathway,
      and implied that BDLNR would be potential therapeutic target for enhancing the
      anti-cancer effects of baicalein in cervical cancer.

PMID- 29175388
TI  - Functional FRIGIDA allele enhances drought tolerance by regulating the P5CS1
      pathway in Arabidopsis thaliana.
AB  - Flowering at the right time is important for the reproductive success of plants
      and their response to environmental stress. In Arabidopsis, a major determinant
      of natural variation in flowering time is FRIGIDA (FRI). In the present study, we
      show that overexpression of the functional FRIGIDA gene in wild-type Col
      background (ColFRI) positively enhances the drought tolerance by activating P5CS1
      expression and promoting proline accumulation during water stress. Furthermore,
      no significant changes in FRI gene and protein expression levels were observed
      with drought treatment, whereas P5CS1 protein expression significantly increased.
      In contrast, vernalization treatment efficiently reduced P5CS1 expression levels
      and resulted in a decrease in drought tolerance in the ColFRI plants. The flc
      mutants with a functional FRI background also relieved FRI-mediated activation of
      P5CS1 during drought tolerance. Taken together, our findings reveal the novel
      function of FRI in enhancing drought resistance through its downstream P5CS1
      pathway during water-deficit stress, which is dependent on its target, the FLC
      gene.

PMID- 29175389
TI  - Repetitive restraint stress changes spleen immune cell subsets through
      glucocorticoid receptor or beta-adrenergic receptor in a stage dependent manner.
AB  - Immune system is sensitive to stress. Spleen is the largest peripheral immune
      organ innervated with sympathetic nerves and controlled by adrenomedullary system
      in the body. However, the alterations and mechanism of spleen immune cell subsets
      caused by repetitive restraint stress (RRS) is poorly understood. In this study,
      we found that RRS reduced spleen index in mice, and induced an expansion of white
      pulp and involution of the red pulp. Meanwhile, the percentage of CD3+CD8+ T
      lymphocytes, CD11b+F4/80+ macrophages, CD11b+Ly-6G-Ly-6Chi monocytic myeloid
      derived suppressor cells (mMDSCs) and CD11b+Ly-6G+Ly-6Cint granulocytic myeloid
      derived suppressor cells (gMDSCs) in spleen were significantly changed by RRS.
      Mechanistically, we found that the expression of norepinephrine (NE) and beta
      adrenergic receptor (beta-AR) in spleen were up-regulated after 21 days of RRS,
      but not 7 days. The expression of corticosterone (CORT) and glucocorticoid
      receptor (GR) in spleen were up-regulated after 7 days of RRS but were lower
      after 21 days of RRS, even though they were still higher than that in mice
      without stress. By treating the stressed mice with RU486 (antagonist of GR) or
      propranolol (antagonist of beta-AR), we demonstrated that GR was responsible for
      the changes of spleen induced by 7 days of RRS and beta-AR was for 21 days of
      RRS. Our data suggest that RRS changes spleen immune cell subsets through GR or
      beta-AR in a stage dependent manner.

PMID- 29175390
TI  - Human adipose-derived stem cells and simvastatin-functionalized biomimetic
      calcium phosphate to construct a novel tissue-engineered bone.
AB  - To repair bone defects, we evaluate the in-vitro and in-vivo osteogenic
      activities of a novel tissue-engineered bone (TEB) by elaborately combining
      biomimetic calcium phosphate (BioCaP) granules with internally-incorporated
      simvastatin (SIM) and human adipose-derived stem cells (hASCs). First, we
      constructed BioCaP with SIM internally incorporated (SIM-BioCaP). Then we
      characterized the morphology and chemical composition of SIM-BioCaP. The release
      kinetics of SIM was monitored in vitro spectroscopically. Thereafter, we explored
      the in-vitro cellular responses of hASCs to SIM-BioCaP by performing scanning
      electron microscopy observation, proliferation assay, alkaline phosphatase (ALP)
      activity assay, alizarin red staining and real-time PCR. Finally, we investigated
      the in-vivo osteogenic activities of the novel TEB in a subcutaneous bone
      induction model in nude mice. We found that SIM was successfully incorporated
      internally in BioCaP and showed a slow release manner without significantly
      affecting the attachment and proliferation of hASCs. The released SIM from BioCaP
      could significantly enhance the proliferation, ALP activities, mineralized
      nodules formation and osteogenic genes of hASCs. The in-vivo tests showed this
      TEB could induce new bone formation while the other groups could not. Taken
      together, the present data show that this novel TEB represented a very promising
      construct to treat critical-volume bone defects.

PMID- 29175392
TI  - Genetic ancestry effects on the distribution of toll-like receptors (TLRs) gene
      polymorphisms in a population of the Atlantic Forest, Sao Paulo, Brazil.
AB  - The innate immune system governed by toll-like receptors (TLRs) provides the
      first line of defense against pathogens. Surface-localized TLR1 and TLR6 are
      known to detect parasite components. TLR encoding genes were shown to display
      signatures of recent positive selection in Europeans and might be involved in
      local adaptation at immune-related genes. To verify the influence of Brazilian
      population admixture on the distribution of polymorphisms in TLRs, we analyzed
      the genotype frequencies of 24 polymorphisms distributed across five TLR genes in
      a Southeastern Brazilian population where autochthonous cases of malaria occur in
      small foci of transmission. The estimation of ancestry showed mainly European
      ancestry (63%) followed by African ancestry (22%). Mean proportions of European
      ancestry differed significantly between the genotypes of the TLR1 (I602S) gene
      and in the TLR6 (P249S) gene. The chance of having the G allele in TLR1 gene
      increases as European ancestry increases as well as the chance of having the T
      allele in the TLR6 gene. The 602S allele is related to a ''hypo-responsiveness''
      possibly explaining the high prevalence of asymptomatic malaria cases in areas of
      Southeastern Brazil. Our results underline the necessity to include informative
      ancestry markers in genetic association studies in order to avoid biased results.

PMID- 29175393
TI  - Total body and arm bioimpedance in patients with Alzheimer's disease.
AB  - PURPOSE OF THE RESEARCH: To analyse body composition of patients with Alzheimer's
      disease (AD) using total body and localized specific bioelectrical impedance
      vector analysis (specific BIVA). METHOD: 127 patients (50 men, 78.2+/-6.3years;
      77 women, 81.4+/-6.8years) with mild to moderate stages of AD were selected from
      the Geriatric Division, SS. Trinita Hospital of Cagliari (Italy). A sample of 135
      healthy age-matched individuals (74 men, 77.4+/-5.3years; 61 women, 80.4+/
      5.5years) was chosen as control group. Anthropometric measurements were taken and
      body mass index (BMI) was calculated. Bioelectrical measurements were taken on
      the right side of the body for both the whole-body and the arm, using a BIA 101
      analyser (Akern). Body composition was assessed by means of specific
      bioelectrical impedance vector analysis (specific BIVA). The comparison between
      patients and the control group was performed by two-factor analysis of variance
      and Hotelling's T2 test. RESULTS: In comparison with the control group, patients
      with AD showed similar anthropometric characteristics, including BMI, but lower
      lean tissue mass and higher percent fat mass, as indicated by the lower phase
      angles and longer specific vectors. The same body composition peculiarities were
      detected considering only the right arm. CONCLUSION: Patients with AD show
      characteristics - lower lean mass/higher percent fat mass - that can be detected
      by both total body and localized bioimpedance approaches. This suggests the
      possibility of a new, quicker and simpler procedure for body composition
      assessment.

PMID- 29175391
TI  - Integrated functional and mass spectrometry-based flow cytometric phenotyping to
      describe the immune microenvironment in acute myeloid leukemia.
AB  - A hallmark of the development of cancer is its ability to avoid detection and
      elimination by the immune system. There are many identified mechanisms of this
      immune evasion that can be measured both phenotypically and functionally.
      Functional studies directly show the ability of the tumor microenvironment to
      suppress immune responses, typically measured as lymphocyte proliferation,
      cytokine production or killing ability. While a direct measurement of function is
      ideal, these assays require ex vivo activation which may not accurately mimic in
      vivo conditions. Phenotypic assays can directly measure the distribution and
      activation of immune cell types rapidly after isolation, preserving the
      conditions present in the patient. While conventional flow cytometry is a rapid
      and well established assay, it currently allows for measurement of only 12-14
      parameters. Mass spectrometry-based flow cytometry, or CyTOF, offers the ability
      to measure 3-fold more parameters than conventional optical-based modalities
      providing an advantage in depth of analysis that can be crucial for precious
      human samples. The goal of this report is to describe the system our group has
      developed to measure both the phenotype and function of immune cells in the bone
      marrow of patients with acute myeloid leukemia. We hope to explain our system in
      the context of previous studies aimed at measuring immune status in tumors and to
      inform the reader as to some experimental approaches our group has found useful
      in developing the basic data required to rationally pursue immune-based therapies
      for patients with cancer.

PMID- 29175394
TI  - Impact of plant photosystems in the remediation of benzo[a]pyrene and pyrene
      spiked soils.
AB  - The phytoremediation potential of 14 different plant species belonging to C3 and
      C4 carbon fixation pathway for soils spiked with polycyclic aromatic hydrocarbons
      (PAHs) such as benzo[a]pyrene (B[a]P) and pyrene (PYR) was investigated. A
      glasshouse experiment was conducted to measure the changes in morphological,
      physiological, biochemical parameters and the bioaccumulation and biodegradation
      ability of the plants in soils spiked with 48 and 194 mg kg-1 of B[a]P and PYR,
      respectively. The per cent removal efficacy of B[a]P and PYR by the tested plant
      species over a period of 50 days was from 6 to 26% and 14 to 40% respectively.
      The maximum removal of both B[a]P and PYR was observed in Sudan grass (C4),
      vetiver (C4), maize (C4), and sunflower (C3). In terms of accumulation in root
      and shoot, the concentration of PYR was higher in both C3 and C4 plant species
      when compared to B[a]P. Overall the results indicated that C4 plants were more
      efficient than their C3 counterparts in terms of morphological, physiological,
      biochemical and degradation ability of PAHs.

PMID- 29175395
TI  - Sorption of albendazole in sediments and soils: Isotherms and kinetics.
AB  - Albendazole is a broad-spectrum anthelmintic drug effective against
      gastrointestinal parasites in humans and animals. Despite the fact that it has
      been detected in environment (water, sediment and soil), there is no information
      on its fate in the environment. So, in order to understand the sorption process
      of albendazole in environment, the sorption mechanism and kinetic properties were
      investigated through sorption equilibrium and sorption rate experiments. For that
      purpose, batch sorption of albendazole on five sediment samples and five soil
      samples from Croatia's region with different physico-chemical properties was
      investigated. Except physico-chemical properties of used environmental solid
      samples, the effects of various parameters such as contact time, initial
      concentration, ionic strength and pH on the albendazole sorption were studied.
      The Kd parameter from linear sorption model was determined by linear regression
      analysis, while the Freundlich and Langmuir sorption models were applied to
      describe the equilibrium isotherms. The estimated Kd values varied from 29.438 to
      104.43 mLg-1 at 0.01 M CaCl2 and for natural pH value of albendazole solution (pH
      6.6). Experimental data showed that the best agreement was obtained with the
      linear model (R2 > 0.99), while the rate of albendazole sorption is the best
      described with the kinetic model of pseudo-second-order. Obtained results point
      to a medium or even strong sorption of albendazole for soil or sediment
      particles, which is particularly dependent on the proportion of organic matter,
      pH, copper and zinc in them.

PMID- 29175396
TI  - Effects of triclosan (TCS) on hormonal balance and genes of hypothalamus
      pituitary- gonad axis of juvenile male Yellow River carp (Cyprinus carpio).
AB  - Triclosan (TCS) is a broad spectrum antimicrobial agent which has been widely
      dispersed and determinated in the aquatic environment. However, the effects of
      TCS on reproductive endocrine in male fish are poorly understood. In this study,
      male Yellow River carp (Cyprinus carpio) were exposed to 0, 1/5, 1/10 and 1/20
      LC50 (96 h LC50 of TCS to carp) TCS under semi-static conditions for 42 d.
      Vitellogenin (Vtg), 17beta-estradiol (E2), testosterone(T), gonadotropin (GtH),
      and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked
      immunosorbent assay (ELISA). Meanwhile, we also examined the mRNA expressions of
      aromatase, GtHs-beta, GnRH, estrogen receptor (Er), and androgen receptor (Ar) by
      quantitative Real-time Polymerase Chain Reaction (qRT-PCR). TCS induced Vtg
      levels of hepatopancreas, E2 levels of serum, and inhibited Ar and Er mRNA
      levels, suggesting that the induction of Vtg production by TCS was indirectly
      caused by non-Er pathways. TCS-induced Vtg levels by interfering with the
      reproductive axis at plenty of latent loci of male carps: (a) TCS exposure
      increased the aromatase mRNA expression of hypothalamus and gonad aromatase,
      consequently increasing serum concentrations of E2 to induce Vtg in
      hepatopancreas; (b) TCS treatment changed GtH-beta and GnRH mRNA expression and
      secretion, causing the disturbance of reproductive endocrine; (c) TCS exposure
      decreased Ar mRNA levels, indicating potential Ar-mediated antiandrogen action.
      These mechanisms showed that TCS may induce Vtg production in male carp by non-Er
      mediated pathways.

PMID- 29175397
TI  - Effect and mechanism analysis of MnO2 on permeable reactive barrier (PRB) system
      for the removal of tetracycline.
AB  - Effect of manganese dioxide (MnO2) on tetracycline (TC) removal/degradation in
      zero-valent iron (ZVI) based permeable reactive barrier (PRB) system was
      investigated. To analyze the role of MnO2, three different PRB columns packed
      with ZVI, ZVI and a layer of MnO2, and MnO2 were set up to investigate the
      removal effect and reaction mechanism of ZVI coupling with MnO2 on TC removal,
      respectively. The results show that the removal efficiencies of three PRB columns
      are 65%, 85%, and 50%, respectively. MnO2 could accelerate the transformation of
      Fe2+ into Fe3+ and combine with Fe3+ to degrade TC in different reaction sites in
      the ZVI-MnO2 PRB system. Hydroxyl radicals (.OH) were produced in this process,
      which contributed to about 58.3% for the TC degradation. The UV-Vis spectrum
      demonstrated that A ring of TC was the main reaction site for interaction with
      Fe3+ and the BCD rings were crucial for interactions with MnO2. On the basis of
      intermediates identified by LC-ESI-MS, the ring structure of TC was opened, and
      low-molecular-weight compounds were produced in ZVI-MnO2 PRB system.

PMID- 29175398
TI  - Toxic effects and mechanism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on
      Lemna minor.
AB  - To investigate the toxic effect and mechanism of 2,2',4,4'-tetrabromodiphenyl
      ether (BDE-47) in aquatic plants, in vivo and in vitro exposure to BDE-47 were
      conducted. After 14-d exposure to 5-20 MUg/L BDE-47, the growth of Lemna minor
      plants was significantly suppressed, and the chlorophyll and soluble protein
      contents in fronds markedly decreased. Accordingly, the photosynthetic efficiency
      (Fv/Fm, PI) decreased. When the thylakoid membranes isolated from healthy fronds
      was exposed to 5-20 mg/L BDE-47 directly in vitro for 1 h, the photosynthetic
      efficiency also decreased significantly. In both the in vitro (5-20 MUg/L) and in
      vivo (5-20 mg/L) experiments, BDE-47 led to an increased plasma membrane
      permeability. Hence, we concluded that BDE-47 had a direct toxicity to
      photosynthetic membranes and plasma membranes. However, direct effects on the
      activities of peroxidase (POD), malate dehydrogenase (MDH) and nitroreductase
      (NR) were not observed by adding 5-20 mg/L BDE-47 into crude enzyme extracts. The
      malondialdehyde (MDA) and superoxide anion radical (O2-) contents in the BDE-47
      treated fronds were higher than those in the control fronds, suggesting that L.
      minor can not effectively relieve reactive oxygen species (ROS). The data above
      indicates that BDE-47 is toxic to L. minor through acting directly on
      biomembranes, which induces the production of ROS and thus causes remarkable
      oxidative damage to cells.

PMID- 29175399
TI  - Leaching of TCIPP from furniture foam is rapid and substantial.
AB  - A series of laboratory experiments were conducted, in which waste furniture
      polyurethane foam samples containing tris (1-chloro-2-propyl) phosphate (TCIPP)
      were contacted with a range of leaching fluids, formulated to simulate the
      composition of landfill leachate. Leaching was examined under a number of
      different scenarios, such as: dissolved humic matter concentration, pH, and
      temperature, as well as the effect of agitation, and waste:leaching fluid contact
      duration. In addition to single batch (no replenishment of leaching fluid),
      serial batch (draining of leachate and replenishment with fresh leaching fluid at
      various time intervals) experiments were conducted. Leaching of TCIPP from PUF
      appears to be a first order process. Concentrations of TCIPP in leachate
      generated by the experiments in this study ranged from 13 mg L-1 to 130 mg L-1.
      In serial batch leaching experiments, >95% of TCIPP was depleted from PUF after
      168 h total contact with leaching fluid. Our experiments indicate leaching is
      potentially a very significant pathway of TCIPP emissions to the environment.

PMID- 29175400
TI  - Revitalisation of metal-contaminated, EDTA-washed soil by addition of unpolluted
      soil, compost and biochar: Effects on soil enzyme activity, microbial community
      composition and abundance.
AB  - Soil remediation mitigates hazards from contaminants but could deprive soils of
      initial biota and enzymes. Historically contaminated acidic soil from Arnoldstein
      (Austria) and calcareous soil from Meza (Slovenia) were washed with 30 and 100
      mmol kg-1 ethylenediaminetetraacetate (EDTA) to remove 78 and 60% of Pb as a main
      pollutant. Remediation of the Arnoldstein soil decreased urease activity and
      increased beta-glucosidase activity, measured in a 15-week experiment. The
      dehydrogenase activity and microbial gene abundances were not significantly
      impeded compared to the original soil. Conversely, the use of a high dose of EDTA
      in the Meza soil, necessary for effective remediation of calcareous soils,
      resulted in pronouncedly decreased enzyme activities (3.2 times on average) and
      repressed fungal ITS and increased bacterial 16S rRNA gene abundance. Remediation
      shifted the microbial community composition in both soils. For revitalisation,
      the remediated soils were amended with compost, inocula of un-contaminated soil
      and (Arnoldstein soil) biochar enriched with soil extract. Amendments
      inconsistently affected the Arnoldstein soil: compost increased the dehydrogenase
      activity and altered the microbial community composition, biochar enhanced the
      beta-glucosidase activity, and all amendments decreased the microbial abundance
      (1.6 times on average). In contrast, amendments efficiently revitalised the
      remediated Meza soil; compost and soil inoculum returned the enzyme activities
      back to the baseline in the original soil, increased the fungal abundance above
      that in the original soil and restored the microbial community composition.

PMID- 29175401
TI  - Mesoporous nanoplate multi-directional assembled Bi2WO6 for high efficient
      photocatalytic oxidation of NO.
AB  - Herein, a mesoporous nanoplate multi-directional assembled Bi2WO6 architecture
      was successfully prepared and applied for the photocatalytic removal of NOx
      pollutants at low concentrations under visible light and simulated solar light
      irradiation. Bi2WO6-180-C synthesized at a hydrothermal temperature of 180 
      degrees C with calcination exhibited an excellent conversion efficiency in the
      photocatalytic oxidation of gaseous NO. The crystallinity, morphology, specific
      surface area, pore environment, light absorption, and separation of
      photogenerated electrons and holes were investigated by various techniques; the
      excellent photocatalytic performance of Bi2WO6-180-C was attributed to its
      special hierarchical mesoporous structure with an appropriate pore size and
      interconnected porous network, which imparted good gas permeability and fast mass
      transfer of reaction intermediates and final products of NO oxidation.
      Furthermore, hierarchical mesoporous Bi2WO6 showed excellent photocatalytic
      durability and reusability.

PMID- 29175402
TI  - Neurobehavioral assessment of rats exposed to pristine polystyrene nanoplastics
      upon oral exposure.
AB  - The increasing use of plastics has raised concerns about pollution of freshwater
      by these polymeric materials. Knowledge about their potential effects on
      environmental and public health is limited. Recent publications have suggested
      that the degradation of plastics will result in the release of nano-sized plastic
      particles to the environment. Therefore, it is of utmost importance to gain
      knowledge about whether and how nanoplastics affect living organisms. The present
      study aimed to analyse potential neurobehavioral effects of polystyrene
      nanoparticles (PS-NPs) after long-term exposure on rat. Potential effects of PS
      NPs were investigated using four test dosages (1, 3, 6, and 10 mg PS-NPs/kg of
      body weight/day) administrated orally with adult Wistar male rats for five weeks.
      Neurobehavioral tests were chosen to assess a variety of behavioral domains.
      Particle diameters in test suspensions were determined through dynamic light
      scattering and showed an average hydrodynamic diameter of approximately 38.92 nm.
      No statistically significant behavioral effects were observed in all tests
      performed (p > 0.05). In the elevated plus maze, PS-NPs-exposed rats showed
      greater number of entries into open arms compared to controls. Also, PS-NPs had
      no significant influence on body weight of animals. Taking into account the
      subtle and transient nature of neurobehavioral consequences, however, these
      results underline the possibility of even pristine plastic nanoparticles to
      induce behavioral alteration in the rest of the food web, including for marine
      biota and humans. Indeed even though studied neurobehavioral effects in our study
      was not statistically significant, the observed subtle effects may be clinically
      considerable.

PMID- 29175403
TI  - Measuring and modeling surface sorption dynamics of organophosphate flame
      retardants on impervious surfaces.
AB  - Understanding the sorption mechanisms for organophosphate flame retardants
      (OPFRs) on impervious surfaces is important to improve our knowledge of the fate
      and transport of OPFRs in indoor environments. The sorption processes of
      semivolatile organic compounds (SVOCs) on indoor surfaces are heterogeneous
      (multilayer sorption) or homogeneous (monolayer sorption). In this study, we
      adopted simplified Langmuir isotherm and Freundlich isotherm in a dynamic sink
      model to characterize the sorption dynamics of OPFRs on impervious surfaces such
      as stainless steel and made comparisons between the two models through a series
      of empty chamber studies. The tests involve two types of stainless steel chambers
      (53-L small chambers and 44-mL micro chambers) using tris(2-chloroethyl)phosphate
      (TCEP) and tris(1-chloro-2-propyl)phosphate (TCPP) as target compounds. Our test
      results show that the dynamic sink model using Freundlich isotherm can better
      represent the sorption process in the empty small chamber. Micro chamber test
      results from this study show that the sink model using both simplified Langmuir
      isotherm and Freundlich isotherm can well fit the measured gas-phase
      concentrations of OPFRs. We further applied both models and the parameters
      obtained to predict the gas phase concentrations of OPFRs in a small chamber with
      an emission source. Comparisons between model predictions and measurements
      demonstrate the reliability and applicability of the sorption parameters.

PMID- 29175404
TI  - Geochemical sources, hydrogeochemical behavior, and health risk assessment of
      fluoride in an endemic fluorosis area, central Iran.
AB  - The present study is the first attempt to put forward the possible source(s) and
      health risk assessment of fluoride in Bahabad, central Iran. Fluoride
      concentrations ranged from 0.22 to 2.35 mg/L and 292-355 mg/kg in the groundwater
      and soil samples, respectively. Geochemical provenance techniques using major and
      rare earth elements in soils revealed that local shale is the most probable
      source rock of fluoride in the area. A two-step chemical fractionation method
      applied on soil samples demonstrated that residual and water-soluble fractions
      were the most probable modes of fluoride in soil, whereas exchangeable fraction
      had a minor role. The coefficient of aqueous migration showed that fluoride in
      the studied soils behaved as a mobile element. Moreover, the relative mobility
      indicated that soils played a more important role than rocks in releasing
      fluoride into groundwater. In groundwater medium, chemical weathering,
      evaporation, and ion exchange acted as the main geochemical controlling factors
      of fluoride enrichment. Findings of this study signify that the role of NaCl and
      NaSO4-type waters should be considered more to recognize susceptible areas to
      fluoride contamination in groundwater. People in the study area are exposed to
      high levels of fluoride intake through drinking water, thus making dental
      fluorosis a major public health concern in the area. Scanning electron microscopy
      of the dentin's enamel showed morphological modifications (e.g., cracks and
      fissures) in residents' enamel structures. The results of this study may lead to
      suitable management strategies to mitigate the endemic fluorosis problem.

PMID- 29175405
TI  - Arsenic concentrations and speciation in wild birds from an abandoned realgar
      mine in China.
AB  - Birds are at a higher level in the food chain; however, the potential
      bioaccumulation and biotransformation of arsenic (As) in birds in As mines has
      rarely been studied. In this study, four passerine bird species (tree sparrow
      [Passer montanus], light-vented bulbul [Pycnonotus sinensis], Garrulax canorus
      [Leucodioptron canorus], and magpie [Pica pica]) were collected from an abandoned
      As mine in China. The highest recorded As concentrations were 4.95 mg/kg and
      51.65 mg/kg in muscles and feathers, respectively. Detection using high
      performance liquid chromatography inductively coupled plasma mass spectrometry
      (HPLC-ICP-MS) revealed six As species, including arsenite (As(III)), arsenate
      (As(V)), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), arsenobetaine
      (AsB) and arsenocholine (AsC), with the former three species as the dominant
      (>92%) and the latter three as the minor As species (<6.17%). Further analysis of
      the selected bird samples using the X-ray absorption near edge structure (XANES)
      technique revealed the existence of As(III)-tris-glutathione (As(III)-GSH), which
      can be regarded as equivalent to the non-extractable and unidentified As form in
      the HPLC-ICP-MS data. Both methods revealed similar patterns of As species in the
      birds from the As mine, with muscles containing mainly inorganic As and DMA and
      feathers containing mainly inorganic As. The results of this study contribute to
      the knowledge regarding As accumulation and speciation in terrestrial organisms.

PMID- 29175406
TI  - Evaluation of carbon isotope fractionation during anaerobic reductive
      dehalogenation of chlorinated and brominated benzenes.
AB  - Compound specific stable isotope analysis (CSIA) has been established as a useful
      tool to evaluate in situ biodegradation. Here, CSIA was used to determine
      microbial dehalogenation of chloro- and bromobenzenes in microcosms derived from
      Hackensack River sediments. Gas chromatography-isotope ratio mass spectrometry
      (GC-IRMS) was used to measure carbon isotope fractionation during reductive
      dehalogenation of hexachlorobenzene (HCB), pentachlorobenzene (PeCB), 1,2,3,5
      tetrachlorobenzene (TeCB), 1,2,3,5-tetrabromobenzene (TeBB), and 1,3,5
      tribromobenzene (TriBB). Strong evidence of isotope fractionation coupled to
      dehalogenation was not observed in the substrate, possibly due to the low
      solubilities of the highly halogenated benzene substrates and a dilution of the
      isotope signal. Nonetheless, we could measure a depletion of the delta13C value
      in the dichlorobenzene product during dechlorination of HCB, the sequential
      depletion and enrichment of delta13C value for trichlorobenzene in TeCB
      dechlorinating cultures, and the enrichment of delta13C during debromination of
      TriBB. This indicates that a measurable isotope fractionation occurred during
      reductive dehalogenation of highly halogenated chloro- and bromobenzenes in
      aquatic sediments. Thus, although more quantitative measurements will be needed,
      the data suggests that CSIA may have application for monitoring in situ microbial
      reductive dehalogenation of highly halogenated benzenes.

PMID- 29175407
TI  - An in situ study of growth of Lemongrass Cymbopogon flexuosus (Nees ex Steud.) W.
      Watson on varying concentration of Chromium (Cr+6) on soil and its
      bioaccumulation: Perspectives on phytoremediation potential and
      phytostabilisation of chromium toxicity.
AB  - Chromium (Cr) contamination in soil is a growing concern in sustainable
      agricultural production and food safety. Remediation of Cr from contaminated
      soils is a challenging task which may not only help in sustaining agriculture but
      also in minimizing adverse environmental impacts. Pot culture experiments were
      performed with the application of varied concentration of Cr+6 to assess the
      Chromium accumulation potential of Lemongrass and to study the impact of toxic
      concentration of Cr+6 on morphological, physiological and biochemical parameters
      of the plant. The results showed an increasing accumulation trend of Chromium
      with increasing Chromium concentrations in both root and shoot of 60 days old
      Lemongrass plants, while the protein and chlorophyll contents decreased.
      Similarly, accumulation of Cr increased the levels of proline and antioxidant
      enzymes indicating the enhanced damage control activity. The potentiality of the
      plant with the capacity to accumulate and stabilize Cr compound in Cr
      contaminated soil by phytoremediation process has been explored in the present
      investigation.

PMID- 29175408
TI  - Circadian variations in the pharmacokinetics of capecitabine and its metabolites
      in rats.
AB  - Capecitabine, an orally available prodrug of 5-fluorouracil, is widely used to
      treat patients with colorectal cancer. Although various studies have shown
      circadian variations in plasma 5-fluorouracil concentrations during long-term
      infusion, it is still unknown whether circadian variations also exist following
      administration of capecitabine. The present study aimed to investigate whether
      the pharmacokinetics of capecitabine and its metabolites, including 5
      fluorouracil, vary according to administration time in rats. Rats were orally
      administered capecitabine (180mg/kg) at 07:00 (23h after light onset, HALO),
      13:00 (5 HALO), or 19:00h (11 HALO). Plasma concentrations of capecitabine and
      its metabolites, such as 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5
      fluorouridine (5'-DFUR), and 5-fluorouracil, were determined after capecitabine
      administration. The results showed that the t1/2 and AUC0-infinity values of 5
      fluorouracil differed as a function of the dosing time of capecitabine. The
      maximum and minimum mean t1/2 values of 5-fluorouracil were obtained when the
      drug was administered at 07:00h (23 HALO: 3.1+/-1.2h) and 13:00h (5 HALO: 1.5+/
      0.6h), respectively. The AUC0-infinity value of 5-fluorouracil at 07:00h (23
      HALO: 533.9+/-195.7MUmol?h/L) was 1.8-fold higher than the value at 13:00h (5
      HALO: 302.5+/-157.1MUmol?h/L). The clearance of 5-fluorouracil followed a cosine
      circadian curve, and the simulated population mean clearance was highest at rest
      times and lowest during active times in rats. The results for the plasma 5'-DFCR
      and 5'-DFUR levels indicated that circadian variations in the sequential
      metabolism of capecitabine to 5-fluorouracil would also affect plasma 5
      fluorouracil levels following capecitabine administration. In conclusion, the
      pharmacokinetics of capecitabine and its metabolites, including 5-fluorouracil,
      varied according to time of dosing, suggesting that the capecitabine
      administration time is an important factor in achieving sufficient efficacy and
      reducing toxicity in patients.

PMID- 29175409
TI  - Are high-sensitivity cardiac troponin I values stable between preoperative visit
      and day of non-cardiac surgery?
AB  - BACKGROUND: It is unclear if cardiac troponin values are stable in patients prior
      to undergoing non-cardiac surgery, or if they tend to rise towards the day of
      surgery. METHODS: In this small pilot study (n=18) among patients with cardiac
      risk undergoing non-cardiac surgery, we determined if high-sensitivity cardiac
      troponin I (hscTnI) changes between the preoperative clinic visit and the day of
      surgery. HscTnI was measured on an Abbott Architect STAT (Abbott Laboratories,
      USA) platform. RESULTS: The mean duration between preoperative clinic visit and
      day of surgery was 8.7+/-2.8 (SD) days. Median hscTnI was 3.4ng/L [2.0-4.8, IQR]
      at the preoperative visit and 2.8ng/L [2.3-4.4] on the day of surgery (mean
      difference-0.24ng/L, 95% CI - 0.73 to 0.24ng/L, p=0.30). Only one patient had a
      large change (>50%) along with symptoms. DISCUSSION: Evidence from this small
      study suggests that cardiac troponin values are stable in most high-risk
      patients, absent clinical events, within 10days prior to non-cardiac surgery.

PMID- 29175410
TI  - InVitro, Ex Vivo, and In Vivo Evaluation of a Dual pH/Redox Responsive
      Nanoliposomal Sludge for Transdermal Drug Delivery.
AB  - A dual pH/redox responsive copper-glyglycine-prednisolone succinate-loaded
      nanoliposomal (NL) sludge was successfully synthesized and optimized using a Box
      Behnken design of experiments. Preformulation design variables indicated that
      relative ratios of phospholipids, considerably influences NL size, thus altering
      the degree of drug loading in the formulation. In vitro evaluation further
      confirmed optimum release kinetics of the NL sludge, corresponding closely to ex
      vivo permeation studies, demonstrating effective transdermal delivery of
      prednisone succinate (PS) through a pig skin model, which closely resembles human
      skin anatomy. The pH/redox stimuli responsiveness of the NL sludge further
      demonstrated superior properties in vivo using a Sprague-Dawley rat model. The NL
      sludge displayed the greatest release of PS within 24 h of evaluation, falling
      within the acceptable therapeutic range of PS dose efficiency. In vivo results
      further displayed the greatest absorption of PS under inflammatory induced
      conditions, thus confirming the unique pH/redox responsive properties of the NL
      sludge. It was thus confirmed that the copper-glyglycine-prednisolone succinate
      loaded NL sludge has significant potential for application in chronic
      inflammatory conditions such as tumor necrosis factor receptor-associated
      periodic syndrome (TRAPS), designed to release an effective dose of
      corticosteroid, as a transdermal drug delivery formulation, for effective
      therapeutic efficacy.

PMID- 29175411
TI  - Mechanistic Physiologically Based Pharmacokinetic (PBPK) Model of the Heart
      Accounting for Inter-Individual Variability: Development and Performance
      Verification.
AB  - Modern model-based approaches to cardiac safety and efficacy assessment require
      accurate drug concentration-effect relationship establishment. Thus, knowledge of
      the active concentration of drugs in heart tissue is desirable along with inter
      subject variability influence estimation. To that end, we developed a mechanistic
      physiologically based pharmacokinetic model of the heart. The models were
      described with literature-derived parameters and written in R, v.3.4.0. Five
      parameters were estimated. The model was fitted to amitriptyline and
      nortriptyline concentrations after an intravenous infusion of amitriptyline. The
      cardiac model consisted of 5 compartments representing the pericardial fluid,
      heart extracellular water, and epicardial intracellular, midmyocardial
      intracellular, and endocardial intracellular fluids. Drug cardiac metabolism,
      passive diffusion, active efflux, and uptake were included in the model as
      mechanisms involved in the drug disposition within the heart. The model accounted
      for inter-individual variability. The estimates of optimized parameters were
      within physiological ranges. The model performance was verified by simulating 5
      clinical studies of amitriptyline intravenous infusion, and the simulated
      pharmacokinetic profiles agreed with clinical data. The results support the model
      feasibility. The proposed structure can be tested with the goal of improving the
      patient-specific model-based cardiac safety assessment and offers a framework for
      predicting cardiac concentrations of various xenobiotics.

PMID- 29175412
TI  - Dissolving Microneedles Loaded With Etonogestrel Microcrystal Particles for
      Intradermal Sustained Delivery.
AB  - The study design is that lipophilic drug was encapsulated within dissolving
      microneedles (DMNs) for sustained-release delivery over 1 week. Etonogestrel
      (ENG), the progestogen used in hormonal contraceptives, was loaded in 2-layered
      DMNs in the form of microcrystal particles (MPs). In vitro release study
      indicated that ENG in the MP form could sustain drug release compared to
      noncrystal form. Hydroxypropyl methylcellulose and polyvinyl alcohol were used to
      prepare the fast dissolving needle tips and flexible back layer, respectively.
      The mechanical strength of microneedles was not affected even with the drug
      loading efficiency of 50.0% in needle tips. The penetration depth of DMNs in
      skin, observed using a confocal laser scanning microscope, was approximately 280
      MUm. The tips of DMNs could be dissolved in rat skin within 1 h with a drug
      delivery efficiency of 63.8 +/- 2.0%. The pharmacokinetic study of DMN treatment
      in rats showed that the plasma levels of ENG were a dose-dependent profile and
      were much steadier than intradermal (ID) injections. There was no statistical
      difference between bioavailability of ENG treated with DMNs or ID injections (p
      >0.05). Therefore, the novel DMNs loaded with drug MP provided a potential
      minimally invasive route for ID sustained delivery of lipophilic drug.

PMID- 29175413
TI  - Status Epilepticus Decreases Brain Cytochrome P450 2D4 Expression in Rats.
AB  - Status epilepticus (SE) is a life-threatening neurological emergency
      characterized by frequent seizures. The present study aims at elucidating the
      effect of SE on CYP2D4 expression in the rat brain. To create a rat model of SE,
      Sprague-Dawley rats were intraperitoneally administered 10 mg/kg kainic acid. The
      CYP2D4 mRNA levels in the cortex and hippocampus of the SE rats were decreased by
      0.38- and 0.39-fold, respectively. The protein level of octamer transcription
      factor 1 (Oct-1), which is involved in the transcriptional activation of CYP2D4
      by binding to the CYP2D4 regulatory element, was also attenuated by 0.64- and
      0.51-fold in these regions of the SE rat, suggesting that a reduction in Oct-1
      may be involved in the CYP2D4 suppression. Yin yang 1 can function as a cofactor
      of histone deacetylase 1 and inhibit the binding of Oct-1 to the CYP2D4
      regulatory element. The coimmunoprecipitation assay revealed that the interaction
      between yin yang 1 and histone deacetylase 1 in the cortex and hippocampus was
      enhanced during SE, indicating that this interaction is also responsible for the
      CYP2D4 suppression. This study clarified that SE led to a decrease in the
      expression of CYP2D4, thus altering the pharmacokinetics and efficacy of the
      drugs in the brain.

PMID- 29175414
TI  - The Effect of Drug Content Reduction on the In Vitro and In Vivo Properties of
      Levonorgestrel-Releasing Intravaginal Rings.
AB  - Intravaginal rings (IVRs) are an option for continuous administration of drugs in
      women. However, a considerable amount of excess drug often remains in the ring
      upon removal. The current study focuses on comparing 2 IVRs releasing
      levonorgestrel (LNG). Both formulations were designed to release 40 MUg of LNG
      daily, however, with a significant difference in the total amount of drug (10.6
      vs. 176.9 mg). Numerical simulations and in vitro release rate testing were
      utilized in designing the IVRs and confirming the similarity of drug release.
      Moreover, a pharmacokinetic (PK) study was performed in 13 healthy Japanese women
      to investigate both formulations during the intended wearing period of 28 days.
      The primary PK metrics was the average concentration of LNG in plasma at defined
      time points under stable conditions. Statistical evaluation of the ratio of the
      main PK metrics indicated values almost in the bioequivalence range. Furthermore,
      drug content determinations for used and unused IVRs were analyzed for confirming
      the expected drug delivery in vivo. In summary, it was shown that with proper
      design, even major differences in the total drug content of IVR formulations
      might not result in significant effects in the in vitro and in vivo release
      properties.

PMID- 29175415
TI  - Multiple overlapping systematic reviews facilitate the origin of disputes: the
      case of thrombolytic therapy for pulmonary embolism.
AB  - OBJECTIVE: To explore disagreements in multiple systematic reviews (SRs)
      assessing the benefit-to-harm ratio of thrombolytic therapy in patients with
      intermediate-risk pulmonary embolism (PE). STUDY DESIGN AND SETTING: MEDLINE,
      EMBASE, Cochrane Database of Systematic Reviews, and Database of Abstracts and
      Reviews of Effectiveness were searched up to April 14, 2016. We included SRs and
      guidelines that evaluated thrombolytic therapy, compared with anticoagulation
      alone, in intermediate-risk PE. We calculated pooled risk ratio (RR) and absolute
      risk difference (RD), with interquartile range (IQR), for all-cause mortality,
      recurrent PE, and major bleeding. RESULTS: We marked the Pulmonary Embolism
      Thrombolysis trial, the largest trial, as a research milestone. Since its release
      in 2014, 12 SRs (2-15 included trials) and two major guidelines were published.
      Studies were concordant in reporting that thrombolysis reduced all-cause
      mortality (median RD -1.55%, IQR -1.60% to -1.40%; median RR 0.55, IQR 0.48
      0.61). Discordant results were found for major bleeding (median RD 4.70%, IQR
      0.90%-5.70%), with SRs reporting results in opposite directions. Relevant
      magnitude of effects and precision for benefits and harms were never
      prespecified. CONCLUSION: Fourteen evidence syntheses were published within 25
      months. Conclusions suggested mortality reduction associated with thrombolytics.
      Therapy harm was more dispersed and alternatively considered. Interpretation of
      the benefit-to-harm ratio was elusive, and modest incremental advantages might or
      not be important, facilitating the origin of disputes.

PMID- 29175416
TI  - Can Autofluorescence Guide Surgeons in the Treatment of Medication-Related
      Osteonecrosis of the Jaw? A Prospective Feasibility Study.
AB  - PURPOSE: The main limitation of surgical treatment of medication-related
      osteonecrosis of the jaw (MRONJ) is difficulty in defining resection margins. The
      aim of this study was to compare the efficacy of the surgeon's experience and
      autofluorescence-guided bone surgery to delimit resection margins for necrotic
      bone. MATERIALS AND METHODS: MRONJ requiring surgical treatment was classified
      according to American Association of Oral and Maxillofacial Surgeons staging. To
      detect vital bone and resection margins, patients of each stage were randomly
      assigned to 1 of 2 surgical groups: an autofluorescence-guided surgery (AF) group
      and a conventional surgery (non-AF) group based on the surgeon's experience. Bone
      samples from the 2 groups were analyzed histopathologically. The main outcomes
      were defined as the absence of bone exposure or infection at the time of
      evaluation. Infection was defined as the presence of swelling, pain, or numbness
      in the area. Measurements were collected preoperatively and 1 week, 1 month, 6
      months, and 1 year after surgery. Statistical analysis included descriptive
      statistics and the Fisher exact test to evaluate eventual differences between the
      2 surgical protocols. RESULTS: The 36 patients (21 women and 15 men) included in
      this study were equally divided into 2 groups according to the surgical protocol:
      18 patients in the non-AF group and 18 in the AF group. Thirty-nine lesions were
      included in this analysis: 20 lesions in the non-AF group and 19 in the AF group.
      Histopathologic examination confirmed the necrotic nature of all bone samples.
      Statistical analysis showed no differences in necrotic bone exposure or signs of
      infections between the 2 surgical protocols at different times (P > .05).
      CONCLUSIONS: Although the VELscope appears to be useful in guiding bone resection
      margins in patients with MRONJ, autofluorescence does not appear to be superior
      to conventional surgical techniques in mucosal healing and quality of life.

PMID- 29175417
TI  - Association Between Polymorphisms in the Genes of Estrogen Receptors and the
      Presence of Temporomandibular Disorders and Chronic Arthralgia.
AB  - PURPOSE: The high prevalence of painful temporomandibular disorders (TMDs) in
      women suggests that estrogen and its receptors play a fundamental etiologic role
      in the development of this joint pathology through complex action mechanisms. The
      aim of this study was to evaluate the possible association between polymorphisms
      in the ESR1 (estrogen receptor-1) and ESRRB (estrogen-related receptor-beta)
      genes and the risk of simultaneous development of TMDs and pain in other joints
      in the body. MATERIALS AND METHODS: All participants were clinically evaluated
      for the presence of TMD (Research Diagnostic Criteria for TMD) and asked about
      the presence of chronic joint pain. The control group consisted of 72 patients
      without TMD and without pain. Participants with arthralgia were divided into 3
      groups: with muscular TMD (n = 42), with articular TMD (n = 16), and without TMD
      and with systemic arthralgia (n = 82). Eight single-nucleotide polymorphisms in
      the ESR1 (rs12154178, rs1884051, rs2273206, rs7774230) and ESRRB (rs1676303,
      rs4903399, rs10132091, rs7151924) genes were investigated. The chi2 test and
      Student t and Mann-Whitney tests were used to assess the relevance of nominal and
      continuous variables, respectively. A P value less than .05 was considered
      significant. RESULTS: The TT (timin/timin) genotype for the ESR1 (rs2273206) gene
      was strongly associated with the risk of developing muscle TMDs and
      temporomandibular joint pain (P = .04). For the ESRRB (rs1676303) gene, an
      association was observed between the CC (cytosine/cytosine) genotype and the
      presence of articular TMDs associated with other chronic arthralgia (P = .02).
      These results were confirmed by the increased risk of developing articular TMDs
      associated with the C allele (P = .04). CONCLUSIONS: This study supports the
      hypothesis that changes in the ESR1 and ESRRB genes influence the presence of
      TMDs associated with chronic joint pain.

PMID- 29175418
TI  - Src family kinase tyrosine phosphorylates Toll-like receptor 4 to dissociate
      MyD88 and Mal/Tirap, suppressing LPS-induced inflammatory responses.
AB  - Src family kinases (SFKs) are a family of protein tyrosine kinases containing
      nine members: Src, Lyn, Fgr, Hck, Lck, Fyn, Blk, Yes, and Ylk. Although SFK
      activation is a major immediate signaling event in LPS/Toll-like receptor 4
      (TLR4) signaling, its precise role has remained elusive due to various
      contradictory results obtained from a certain SFK member-deficient mice or cells.
      The observed inconsistencies may be due to the compensation or redundancy by
      other SFKs upon a SFK deficiency. The chemical rescuing approach was suggested to
      induce temporal and precise SFK activation in living cells, thereby limiting the
      chance of cellular adaption to a SFK-deficient condition. Using the rescuing
      approach, we demonstrate that restoring SFK activity not only induces tyrosine
      phosphorylation of TLR4, but also inhibits LPS-induced NFkappaB and JNK1/2
      activation and consequently suppresses LPS-induced cytokine production. TLR4
      normally recruits TIR domain-containing adaptors in response to LPS, however,
      temporally restored SFK activation disrupts the LPS-induced association of MyD88
      and Mal/Tirap with TLR4. Additionally, using kinase-dead SFK-Lyn (Y397/508F) and
      constitutively active SFK-Lyn (Y508F), we found that the kinase-dead SFK inhibits
      TLR4 tyrosine phosphorylation with reduced binding affinity to TLR4, while the
      kinase-active SFK strongly binds to TLR4 and promotes TLR4 tyrosine
      phosphorylation, suggesting that SFK kinase activity is required for TLR4
      tyrosine phosphorylation and TLR4-SFK interaction. Together, our results
      demonstrate that SFK activation induces TLR4 tyrosine phosphorylation,
      consequently dissociating MyD88 and Mal/Tirap from TLR4 and inhibiting LPS
      induced inflammatory responses, suggesting a negative feedback loop regulated by
      SFK-induced tyrosine phosphorylation in TLR4.

PMID- 29175419
TI  - Exogenous oxidants activate nuclear factor kappa B through Toll-like receptor 4
      stimulation to maintain inflammatory phenotype in macrophage.
AB  - Disturbances in redox equilibrium in tissue can lead to inflammatory state, which
      is a mediatory factor in many human diseases. The mechanism(s) by which exogenous
      oxidants may activate an inflammatory response is not fully understood. Emerging
      evidence suggests that oxidant-induced Toll-like receptor 4 (TLR4) activation
      plays a major role in "sterile" inflammation. In the present study, we used
      murine macrophage RAW-Blue cells, which are chromosomally integrated with
      secreted embryonic alkaline phosphatase (SEAP) inducible by NF-kappaB. We
      confirmed the expression of TLR4 mRNA and protein in RAW-Blue cells by RT-PCR and
      Western blot, respectively. We showed that oxidants increased intracellular
      reactive oxygen species production and lipid peroxidation, which resulted in
      decreased intracellular total antioxidant capacity. Consistent with the actions
      of TLR4-specific agonist LPS-EK, exogenous oxidants increased transcriptional
      activity of NF-kappaB p65 with subsequent release of NF-kappaB reporter gene
      SEAP. These effects were blocked by pretreatment with TLR4 neutralizing pAb and
      TLR4 signaling inhibitor CLI-095. In addition, oxidants decreased the expression
      of IkappaBalpha with enhanced phosphorylation at the Tyr42 residue. Finally,
      oxidants and LPS-EK increased TNFalpha production, but did not affect IL-10
      production, which may cause imbalance between pro- and anti-inflammatory
      processes, which CLI-095 inhibited. For biological relevance, we confirmed that
      oxidants increased release of TNFalpha and IL-6 in primary macrophages derived
      from TLR4-WT and TLR4-KO mice. Our results support the involvement of TLR4
      mediated oxidant-induced inflammatory phenotype through NF-kappaB activation in
      macrophages. Thus exogenous oxidants may play a role in activating inflammatory
      phenotypes that propagate and maintain chronic disease states.

PMID- 29175420
TI  - alpha1A-Adrenoceptors activate mTOR signalling and glucose uptake in
      cardiomyocytes.
AB  - The capacity of G protein-coupled receptors to modulate mechanistic target of
      rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link
      cell surface receptors with cell survival. Cardiomyocyte viability is linked to
      signalling pathways involving Akt and mTOR, as well as increased glucose uptake
      and utilization. Our aim was to determine whether the alpha1A-adrenoceptor (AR)
      couples to these protective pathways, and increased glucose uptake. We
      characterised alpha1A-AR signalling in CHO-K1 cells co-expressing the human
      alpha1A-AR and GLUT4 (CHOalpha1AGLUT4myc) and in neonatal rat ventricular
      cardiomyocytes (NRVM), and measured glucose uptake, intracellular Ca2+
      mobilization, and phosphorylation of mTOR, Akt, 5' adenosine monophosphate
      activated kinase (AMPK) and S6 ribosomal protein (S6rp). In both systems,
      noradrenaline and the alpha1A-AR selective agonist A61603 stimulated glucose
      uptake by parallel pathways involving mTOR and AMPK, whereas another alpha1-AR
      agonist oxymetazoline increased glucose uptake predominantly by mTOR. All
      agonists promoted phosphorylation of mTOR at Ser2448 and Ser2481, indicating
      activation of both mTORC1 and mTORC2, but did not increase Akt phosphorylation.
      In CHOalpha1AGLUT4myc cells, siRNA directed against rictor but not raptor
      suppressed alpha1A-AR mediated glucose uptake. We have thus identified mTORC2 as
      a key component in glucose uptake stimulated by alpha1A-AR agonists. Our findings
      identify a novel link between the alpha1A-AR, mTORC2 and glucose uptake, that
      have been implicated separately in cardiomyocyte survival. Our studies provide an
      improved framework for examining the utility of alpha1A-AR selective agonists as
      tools in the treatment of cardiac dysfunction.

PMID- 29175422
TI  - Targeting CXCR7 improves the efficacy of breast cancer patients with tamoxifen
      therapy.
AB  - Chemokine (C-X-C motif) receptor 7 (CXCR7) has been established to be involved in
      breast cancer (BCa) progression. However, the role of CXCR7 in different subtype
      of BCa still remains unclear. Here we note that CXCR7 expression is significantly
      amplified in Luminal type BCa tissues as compared with Her2 and TNBC types
      through data-mining in TCGA datasets, and its protein level positively correlates
      with ERalpha expression by staining of human BCa tissue. Interestingly,
      alteration of CXCR7 expression in Luminal type BCa cells is able to modulate the
      expression of ERalpha through ubiquitination at post-translational level.
      Additionally, overexpression of CXCR7 in these cells greatly induces 4-OHT
      insensitivity in vitro and is associated with earlier recurrence in patients with
      tamoxifen therapy. Notably, silencing ERalpha expression potentially rescues the
      sensitivity of the above cells to 4-OHT, suggesting that elevated level of
      ERalpha is responsible for CXCR7-induced 4-OHT insensitivity in Luminal type BCa.
      Finally, mechanistic analyses show that the reduced BRCA1 (ubiquitin E3 ligase)
      and elevated OTUB1 (deubiquitinase) expression, which are regulated by
      CXCR7/ERK1/2 signaling pathway, are responsible for stabilizing ERalpha protein.
      In conclusion, our results suggest that targeting CXCR7 may serve as a potential
      therapeutic strategy for improving the efficacy of BCa patients with tamoxifen
      therapy.

PMID- 29175423
TI  - Tropisetron enhances recognition memory in rats chronically treated with
      risperidone or quetiapine.
AB  - While impairments of cognition in schizophrenia have the greatest impact on long
      term functional outcome, the currently prescribed treatments, antipsychotic drugs
      (APDs), do not effectively improve cognition. Moreover, while more than 20 years
      have been devoted to the development of new drugs to treat cognitive deficits in
      schizophrenia, none have been approved to date. One area that has not been given
      proper attention at the preclinical or clinical stage of drug development is the
      chronic medication history of the test subject. Hence, very little is known about
      how chronic treatment with drugs that affect multiple receptors like APDs
      influence the response to a potential pro-cognitive agent. Therefore, the purpose
      of this study was to evaluate the alpha7 nicotinic acetylcholine receptor (alpha7
      nAChR) partial agonist, tropisetron in rats chronically treated with APDs with
      distinct pharmacological profiles. Rats were treated orally with either
      risperidone (2.5 mg/kg/day) or quetiapine (25.0 mg/kg/day) for 30 or 90 days and
      then an acute injection of vehicle or tropisetron (3.0 mg/kg) was administered
      before training in a novel object recognition (NOR) task. After a 48 h delay
      (when recollection of the familiar object was impaired in vehicle-treated
      animals) neither 30 nor 90 days of risperidone or quetiapine treatment improved
      NOR performance. In contrast, tropisetron markedly improved NOR performance in
      rats treated with either APD for 30 or 90 days. These animal data reinforce the
      argument that two commonly prescribed APDs are not pro-cognitive agents and that
      alpha7 nAChR ligands like tropisetron have potential as adjunctive treatments in
      schizophrenia.

PMID- 29175421
TI  - A review of hydrogen sulfide (H2S) donors: Chemistry and potential therapeutic
      applications.
AB  - Hydrogen sulfide (H2S) is a ubiquitous small gaseous signaling molecule, playing
      an important role in many physiological processes and joining nitric oxide and
      carbon monoxide in the group of signaling agents termed gasotransmitters.
      Endogenous concentrations of H2S are generally low, making it difficult to
      discern precise biological functions. As such, probing the physiological roles of
      H2S is aided by exogenous delivery of the gas in cell and animal studies. This
      need for an exogenous source of H2S provides a unique challenge for chemists to
      develop chemical tools that facilitate the study of H2S under biological
      conditions. Compounds that degrade in response to a specific trigger to release
      H2S, termed H2S donors, include a wide variety of functional groups and delivery
      systems, some of which mimic the tightly controlled endogenous production in
      response to specific, biologically relevant conditions. This review examines a
      variety of H2S donor systems classified by their H2S-releasing trigger as well as
      their H2S release profiles, byproducts, and potential therapeutic applications.

PMID- 29175424
TI  - New spectrophotometric assay for assessments of catalase activity in biological
      samples.
AB  - A novel, simple, and accurate colorimetric assay was established for assessments
      of catalase activity in biological fluids and tissues. H2O2 dissociation rates
      are directly proportional to catalase activity, and the principle of the present
      assay is based on reactions of ammonium metavanadate with H2O2 under acidic
      conditions. The resulting reduction of vanadium (V) to vanadium (III) produces a
      red-orange peroxovanadium complex with absorbance maxima at 452 nm. Biological
      samples containing catalase were incubated with 50-mM phosphate buffer solution
      containing 10-mM H2O2 as a substrate for two min. Subsequently, ammonium
      metavanadate in sulfuric acid was used as an indicator reagent and was added to
      reaction mixtures to determine remaining H2O2 concentrations. The precision of
      the present novel assay was indicated by coefficients of variation of 4.09%
      within runs and 2.56% between runs. Moreover, in experiments with homogenized red
      blood cell solutions, peroxovanate and dichromate assays of catalase activities
      were highly correlated (r = 0.993). In further experiments, we demonstrated
      application of the peroxovanadate method to assessments of catalase activity in
      bacterial and liver homogenates. The present method is accurate, simple, rapid,
      and inexpensive and can be used for routine clinical measurements and scientific
      investigations.

PMID- 29175425
TI  - Modelling the effects of cutting off infected branches and replanting on fire
      blight transmission using Filippov systems.
AB  - Fire blight is one of the most devastating plant diseases in the world. This
      paper proposes a Filippov fire-blight model incorporating cutting off infected
      branches and replanting susceptible trees. The Filippov-type model is formulated
      by considering that no control strategy is taken if the number of infected trees
      is less than an infected threshold level Ic; further, we cut off infected
      branches once the number of infected trees exceeds Ic; meanwhile, we replant
      trees if the number of susceptible trees is less than a susceptible threshold
      level Sc. The global dynamical behaviour of the Filippov system is investigated.
      It is shown that model solutions ultimately converge to the positive equilibrium
      that lies in the region above Ic, or below Ic, or on I=Ic, as we vary the
      susceptible and infected threshold values Sc and Ic. Our results indicate that
      proper combinations of the susceptible and infected threshold values based on the
      threshold policy can lead the number of infected trees to an acceptable level,
      when complete eradication is not economically desirable.

PMID- 29175426
TI  - Competition of energy between active transport and vesicle fusion at the origin
      of intracellular gradient fields.
AB  - It has been reported that the ionic patterns of hyphal growth can be explained by
      a weakening of the active transport at the tip at the expense of other
      biosynthesis processes, from which results energy transport from the proximal
      cells to the apical ones (Potapova et al. 1988). We present here a theory to
      support this hypothesis, whose extent is much more general than the initial frame
      where it has been formulated. It can be summarized in two basics mechanisms, one
      coupling active transport of the plasma membrane, electric potential and vesicle
      fusion, the other coupling the Ca2+-ATPase of the endoplasmic reticulum and
      vesicle fusion. For some values of parameters introduced in the theory, the
      uniform state of the cell becomes unstable, at the origin of intracellular
      gradient fields. Theoretical ionic patterns are spontaneously produced, which can
      be satisfactorily compared to several observed in and around tip-growing cells.

PMID- 29175427
TI  - Therapeutic drug monitoring of ponatinib using a simple high-performance liquid
      chromatography method in Japanese patients.
AB  - A simple and highly sensitive high-performance liquid chromatography (HPLC)
      method was developed for the quantification of ponatinib in human plasma. The
      developed HPLC method was validated based on International D.S. Food and Drug
      Administration guidelines. This technique utilized a solid-phase extraction step
      and required only 200MUL plasma for a single analysis. The lower limit of
      quantification for ponatinib was 1.0ng/mL. Coefficients of variation and
      accuracies for intra- and interday assays were less than 10.8% and within 13.7%,
      respectively. The precision and accuracy of our HPLC assay was suitable for
      pharmacokinetic studies of ponatinib. On day 8 after beginning ponatinib therapy
      with an initial dose of 15mg, patients having a ponatinib C0 of less than 23ng/mL
      by HPLC may require a dose adjustment to 30mg to obtain a C0 of 23ng/mL of more.
      The median ponatinib C0 in 6 Japanese patients taking a 15mg daily dose was
      24.6ng/mL, which was greater than the target concentration of 23ng/mL, and that
      of patients taking 30mg increased to a plasma concentration of 48.0ng/mL. This
      novel treatment strategy using the HPLC method developed herein may be useful for
      routine ponatinib therapy.

PMID- 29175428
TI  - Developing an in vitro artificial sebum model to study Propionibacterium acnes
      biofilms.
AB  - AIM: The aim of the present study was to develop a new model system to study
      Propionibacterium acnes biofilms. This model should be representative for the
      conditions encountered in the pilosebaceous unit. METHODS AND RESULTS: The new
      model, consists of an artificial sebum pellet supported by a silicone disc. Sebum
      pellets were inoculated with various P. acnes strains isolated from both normal
      and acneic skin. Growth and biofilm formation was verified by conventional
      plating at different time points, as well as by resazurin assays and fluorescence
      microscopy after LIVE/DEAD staining. The artificial sebum pellets were also used
      in assays to measure the production of certain virulence factors implicated in
      the pathogenesis of acne, including lipase, protease and the presence of CAMP
      factors. CONCLUSION: The artificial sebum model can sustain biofilm growth of P.
      acnes, as was determined by increasing CFU counts for up to 1 week after
      inoculation. Metabolic activity and biofilm formation were confirmed using
      resazurin staining and fluorescence microscopy respectively. The production of
      virulence factors in this model was demonstrated as well.

PMID- 29175429
TI  - An exploratory open-label, investigator-initiated study to evaluate the efficacy
      and safety of combination sonidegib and buparlisib for advanced basal cell
      carcinomas.

PMID- 29175430
TI  - Medical Students' Acquisition of Adolescent Interview Skills after Coached Role
      Play.
AB  - STUDY OBJECTIVE: To develop and evaluate an educational activity designed to
      teach the adolescent Home, Education and employment, Eating, Activities, Drugs,
      Sexuality, Suicide/depression, and Safety (HEADS) examination. DESIGN, SETTING,
      PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Participants were third
      year medical students in their pediatric clerkships. Students received an article
      on the HEADS interview and attended an adolescent medicine educational session.
      The session included individualized goal-setting and coached role play. Students'
      skills in doing a HEADS interview were evaluated through a standardized patient
      encounter (SPE) with a checklist and a retrospective pre- and post-test survey.
      The SPE checklist was used to assess whether the students included questions in 6
      key areas of a HEADS interview. RESULTS: One hundred fifty-two students
      participated. During the SPE, 90% of students queried the adolescent's home life,
      91% education, 82% activities, 84% drug/substance abuse, 95% sexual history, and
      61% symptoms of depression. Pre- and postintervention data were compared using
      the Kruskal-Wallis Test and showed a statistically significant difference in the
      students' ability to list key topic areas of the HEADS exam (P < .001) and to use
      the skills needed for an adolescent interview using the HEADS exam (P < .001).
      CONCLUSION: After an introduction to the HEADS examination, most students covered
      almost all of the topic areas of this screening interview during a SPE. Only
      three-fifths of the students, however, included questions about symptoms of
      depression. Coached role play with goal-setting facilitated effective learning of
      this approach to adolescent interviewing.

PMID- 29175431
TI  - A cloud-based framework for large-scale traditional Chinese medical record
      retrieval.
AB  - INTRODUCTION: Electronic medical records are increasingly common in medical
      practice. The secondary use of medical records has become increasingly important.
      It relies on the ability to retrieve the complete information about desired
      patient populations. How to effectively and accurately retrieve relevant medical
      records from large- scale medical big data is becoming a big challenge.
      Therefore, we propose an efficient and robust framework based on cloud for large
      scale Traditional Chinese Medical Records (TCMRs) retrieval. METHODS: We propose
      a parallel index building method and build a distributed search cluster, the
      former is used to improve the performance of index building, and the latter is
      used to provide high concurrent online TCMRs retrieval. Then, a real-time multi
      indexing model is proposed to ensure the latest relevant TCMRs are indexed and
      retrieved in real-time, and a semantics-based query expansion method and a multi-
      factor ranking model are proposed to improve retrieval quality. Third, we
      implement a template-based visualization method for displaying medical reports.
      RESULTS: The proposed parallel indexing method and distributed search cluster can
      improve the performance of index building and provide high concurrent online
      TCMRs retrieval. The multi-indexing model can ensure the latest relevant TCMRs
      are indexed and retrieved in real-time. The semantics expansion method and the
      multi-factor ranking model can enhance retrieval quality. The template-based
      visualization method can enhance the availability and universality, where the
      medical reports are displayed via friendly web interface. CONCLUSIONS: In
      conclusion, compared with the current medical record retrieval systems, our
      system provides some advantages that are useful in improving the secondary use of
      large-scale traditional Chinese medical records in cloud environment. The
      proposed system is more easily integrated with existing clinical systems and be
      used in various scenarios.

PMID- 29175432
TI  - DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a
      classical nuclear import pathway.
AB  - MLH1 and PMS2 proteins form the MutLalpha heterodimer, which plays a major role
      in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are
      associated with cancer, especially with colon cancer. The N-terminal region of
      MutLalpha comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal
      region of MutLalpha is composed by the C-termini of PMS2 and MLH1, and the two
      are connected by linker region. The nuclear localization sequences (NLSs)
      necessary for the nuclear transport of the two proteins are found in this linker
      region. However, the exact NLS sequences have been controversial, with different
      sequences reported, particularly for MLH1. The individual components are not
      imported efficiently, presumably due to their C-termini masking their NLSs. In
      order to gain insights into the nuclear transport of these proteins, we solved
      the crystal structures of importin-alpha bound to peptides corresponding to the
      supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to
      study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to
      importin-alpha as monopartite NLSs, which is in agreement with some previous
      studies. However, MLH1-NLS has the highest affinity measured by a natural NLS
      peptide, suggesting a major role of MLH1 protein in nuclear import compared to
      PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the
      MutLalpha heterodimer is discussed.

PMID- 29175433
TI  - Detection of AmpC beta-lactamase-producing Gram-negative bacteria by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - BACKGROUND: Rapid detection of AmpC-producing strains of Gram-negative bacteria
      is beneficial for patient care. Matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF MS) is a novel method that has
      demonstrated the resistance of a strain to beta-lactam antibiotics by determining
      the molecular structure of an antibiotic and its degradation products. AIM: To
      study the detection of AmpC-producing Gram-negative bacteria by MALDI-TOF MS and
      to determine whether the method can be used in clinical practice. METHODS: A
      total of 105 strains were detected by determining their phenotypes and sequence
      analysis. Sixty-nine well-characterized AmpC-producing and 36 non-AmpC-producing
      strains were studied. The bacteria were incubated in different reaction buffer
      solutions (10 mM NH4HCO3/0.005% sodium dodecyl sulphate at pH 8.0) containing
      cefotaxime (0.50 mg/mL), ceftazidime (0.25 mg/mL), ceftriaxone (0.50 mg/mL),
      cefepime (0.50 mg/mL), and cefoxitin (0.25 and 0.50 mg/mL), respectively. The
      mixture was centrifuged at 13,000 g for 2 min, and the supernatant analysed by
      MALDI-TOF MS after incubation for 30, 60, 90, 120, and 240 min. Antibiotic
      hydrolysed and decarboxylated peaks were identified. FINDINGS: When incubated for
      90 min, hydrolysed cefotaxime formed peaks at 434 and 494 Da, and the sensitivity
      and specificity for detection of AmpC-producing strains were 85.5% (59/69) and
      88.9% (32/36). When incubated for 4 h, hydrolysed ceftazidime formed peaks at 563
      and 587 Da, and the sensitivity and specificity were 89.9% (62/69) and 94.5%
      (34/36), respectively. For hydrolysed ceftriaxone (0.5 mg/mL), cefepime (0.5
      mg/mL) and two concentrations of cefoxitin (0.25 and 0.5 mg/mL), no peaks
      amenable to analysis were identified. CONCLUSION: This study demonstrated that
      MALDI-TOF MS can rapidly detect AmpC-producing strains.

PMID- 29175434
TI  - Intensive care unit (ICU)-acquired bacteraemia and ICU mortality and discharge:
      addressing time-varying confounding using appropriate methodology.
AB  - BACKGROUND: Studies often ignore time-varying confounding or may use
      inappropriate methodology to adjust for time-varying confounding. AIM: To
      estimate the effect of intensive care unit (ICU)-acquired bacteraemia on ICU
      mortality and discharge using appropriate methodology. METHODS: Marginal
      structural models with inverse probability weighting were used to estimate the
      ICU mortality and discharge associated with ICU-acquired bacteraemia among
      patients who stayed more than two days at the general ICU of a London teaching
      hospital and remained bacteraemia-free during those first two days. For
      comparison, the same associations were evaluated with (i) a conventional Cox
      model, adjusting only for baseline confounders and (ii) a Cox model adjusting for
      baseline and time-varying confounders. FINDINGS: Using the marginal structural
      model with inverse probability weighting, bacteraemia was associated with an
      increase in ICU mortality (cause-specific hazard ratio (CSHR): 1.29; 95%
      confidence interval (CI): 1.02-1.63) and a decrease in discharge (CSHR: 0.52; 95%
      CI: 0.45-0.60). By 60 days, among patients still in the ICU after two days and
      without prior bacteraemia, 8.0% of ICU deaths could be prevented by preventing
      all ICU-acquired bacteraemia cases. The conventional Cox model adjusting for time
      varying confounders gave substantially different results [for ICU mortality,
      CSHR: 1.08 (95% CI: 0.88-1.32); for discharge, CSHR: 0.68 (95% CI: 0.60-0.77)].
      CONCLUSION: In this study, even after adjusting for the timing of acquiring
      bacteraemia and time-varying confounding using inverse probability weighting for
      marginal structural models, ICU-acquired bacteraemia was associated with a
      decreased daily ICU discharge risk and an increased risk of ICU mortality.

PMID- 29175435
TI  - Antiplatelet effect of aspirin during 24h in patients with type 2 diabetes
      without cardiovascular disease.
AB  - INTRODUCTION: The antiplatelet effect of low-dose aspirin in patients with type 2
      diabetes (T2DM) without cardiovascular disease (CVD) has not been thoroughly
      explored. We investigated if platelet aggregation increased during the standard
      24-hour aspirin dosing interval in patients with T2DM compared to non-diabetic
      controls. Furthermore, we evaluated baseline platelet aggregation, the acute
      effects of aspirin on platelet aggregation and platelet turnover. MATERIALS AND
      METHODS: We included 21 patients with T2DM and 21 age and sex-matched controls.
      Platelet aggregation was measured by impedance aggregometry (Multiplate(r)
      Analyzer) and markers of platelet turnover by flow cytometry (Sysmex(r) XE-5000).
      Blood samples were obtained at baseline and 1h after administration of 75mg of
      aspirin. Participants were then treated for 6days with once-daily aspirin, and
      blood sampling was repeated 1h and 24h after aspirin intake. RESULTS: After 6days
      of treatment, platelet aggregation levels increased during the 24-hour aspirin
      dosing interval in both patients and controls (p<0.001) with no difference
      between patients and controls. At baseline, patients with diabetes had increased
      platelet aggregation compared to controls (p=0.03). Platelet aggregation was
      reduced after the first dose of aspirin and significantly further reduced after
      six days of treatment (p<0.001). Patients with T2DM had numerically higher
      immature platelet count compared to controls (p=0.09), indicating an increased
      platelet turnover. CONCLUSION: Patients with T2DM without a history of CVD and
      controls had increased platelet aggregation at the end of the standard 24-hour
      dosing interval of aspirin. Further, aspirin-naive T2DM patients had increased
      platelet aggregation compared to controls.

PMID- 29175436
TI  - 3D Chromatin Architecture of Large Plant Genomes Determined by Local A/B
      Compartments.
AB  - The spatial organization of the genome plays an important role in the regulation
      of gene expression. However, the core structural features of animal genomes, such
      as topologically associated domains (TADs) and chromatin loops, are not prominent
      in the extremely compact Arabidopsis genome. In this study, we examine the
      chromatin architecture, as well as their DNA methylation, histone modifications,
      accessible chromatin, and gene expression, of maize, tomato, sorghum, foxtail
      millet, and rice with genome sizes ranging from 0.4 to 2.4 Gb. We found that
      these plant genomes can be divided into mammalian-like A/B compartments. At
      higher resolution, the chromosomes of these plants can be further partitioned to
      local A/B compartments that reflect their euchromatin, heterochromatin, and
      polycomb status. Chromatins in all these plants are organized into domains that
      are not conserved across species. They show similarity to the Drosophila
      compartment domains, and are clustered into active, polycomb, repressive, and
      intermediate types based on their transcriptional activities and epigenetic
      signatures, with domain border overlaps with the local A/B compartment junctions.
      In the large maize and tomato genomes, we observed extensive chromatin loops.
      However, unlike the mammalian chromatin loops that are enriched at the TAD
      border, plant chromatin loops are often formed between gene islands outside the
      repressive domains and are closely associated with active compartments. Our study
      indicates that plants have complex and unique 3D chromatin architectures, which
      require further study to elucidate their biological functions.

PMID- 29175437
TI  - An Uncanonical CCCH-Tandem Zinc-Finger Protein Represses Secondary Wall Synthesis
      and Controls Mechanical Strength in Rice.
AB  - Secondary walls, which represent the bulk of biomass, have a large impact on
      plant growth and adaptation to environments. Secondary wall synthesis is switched
      and regulated by a sophisticated signaling transduction network. However, there
      is limited understanding of these regulatory pathways. Here, we report that ILA1
      interacting protein 4 (IIP4) can repress secondary wall synthesis. IIP4 is a
      phosphorylation substrate of an Raf-like MAPKKK, but its function is unknown. By
      generating iip4 mutants and relevant transgenic plants, we found that lesions in
      IIP4 enhance secondary wall formation. Gene expression and transactivation
      activity assays revealed that IIP4 negatively regulates the expression of MYB61
      and CESAs but does not bind their promoters. IIP4 interacts with NAC29/NAC31, the
      upstream regulators of secondary wall synthesis, and suppresses the downstream
      regulatory pathways in plants. Mutagenesis analyses showed that phosphomimic IIP4
      proteins translocate from the nucleus to the cytoplasm, which releases
      interacting NACs and attenuates its repression function. Moreover, we revealed
      that IIPs are evolutionarily conserved and share unreported CCCH motifs, referred
      to as uncanonical CCCH-tandem zinc-finger proteins. Collectively, our study
      provides mechanistic insights into the control of secondary wall synthesis and
      presents an opportunity for improving relevant agronomic traits in crops.

PMID- 29175438
TI  - Gestational 3,3',4,4',5-pentachlorobiphenyl (PCB 126) exposure disrupts
      fetoplacental unit: Fetal thyroid-cytokines dysfunction.
AB  - Exposure to polychlorinated biphenyls (PCBs) is related to several endocrine
      disorders. This study examined the effect of maternal exposure of 3,3',4,4',5
      pentachlorobiphenyl (PCB 126) on the fetoplacental unit and fetal thyroid
      cytokine axis during the pregnancy. Pregnant albino rats received PCB 126 (20 or
      40MUg/kgb.wt.) by oral gavage from gestation day (GD) 1 to 20. Potential effects
      of PCB 126 were evaluated by following the histopathological changes in the
      placenta by Haematoxylin and Eosin (H&E) stain and measuring the maternofetal
      thyroid axis (ELIZA), maternofetal body weight, and fetal growth markers (ELIZA),
      and cytokines (ELIZA) at embryonic day (ED) 20. Placental tissues of both treated
      groups showed hyperemia, hemorrhage, degeneration and apoptosis in labyrinth
      layer and spiral artery at GD 20. Both administrations of PCB 126 elevated serum
      thyrotropin (TSH) concentration, and decreased free thyroxine (FT4) and free
      triiodothyronine (FT3) concentrations, resulting in a maternofetal
      hypothyroidism. The presence of hypothyroidism increased fetal serum
      concentration of transforming growth factor-beta (TGF-beta), leptin (LEP), tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and decreased
      the fetal serum insulin growth factor-I (IGF-I), IGF-II, insulin, adiponectin
      (ADP), and growth hormone (GH) in both treated groups at ED 20. However, the
      increase in resistin (RETN) and interferon-gamma (IFN-gamma) was non-significant
      in low-dose group and highly significant in high-dose group. Simultaneously, the
      reduction in body weight of the dams and fetuses was observed in both PCB 126
      groups of examined day with respect to the control group. The maternal PCB 126
      distorted the fetoplacental unit might disrupt the fetal thyroid-cytokines axis
      and prenatal development.

PMID- 29175439
TI  - Lipid coated chitosan-DNA nanoparticles for enhanced gene delivery.
AB  - Chitosan as a polycationic non-viral vector for gene delivery has the advantage
      of being a biocompatible and biodegradable polymer. However, without laborious
      chemical modifications to its structure, it is of limited use as a gene delivery
      vehicle due to its low ability to efficiently transfect under physiological
      conditions. To address this problem, we developed novel liposome encapsulated
      chitosan nanoparticles; lipochitoplexes (LCPs). Chitosan nanoparticles (CsNPs)
      were obtained using the ionic gelation technique. For this purpose, an ultrapure
      low molecular weight chitosan with a high degree of deacetylation was cross
      linked using polyanionic tripolyphosphate resulting in efficient entrapment of
      plasmid DNA (pDNA) inside the nanoparticles. LCPs were prepared by incubating
      chitosan nanoparticles together with anionic liposomes (DPPC/Cholesterol). The
      LCPs offered better pDNA protection, reduced cytotoxicity and at least twofold
      increase in the transfection efficiency under physiological conditions. The
      efficiency of our delivery vehicle was also proved in vivo in the chorioallantoic
      membrane model (CAM). LCPs were able to transfect the CAM without traumatising
      the surrounding blood vessels. This new biocompatible composite system devoid of
      chemical modifications, organic solvents and harsh production conditions makes it
      an optimal gene delivery vehicle for in vivo applications offering new insights
      into the field of non-viral gene therapy.

PMID- 29175440
TI  - Liposomes encapsulating native and cyclodextrin enclosed paclitaxel: Enhanced
      loading efficiency and its pharmacokinetic evaluation.
AB  - Combination strategy involving cyclodextrin (CD) complexation and liposomal
      system was investigated for Paclitaxel (PTX) to improve loading. Complexation was
      done using 2,6-di-O-methylbetacyclodextrin (DMbetaCD). Sterically stabilized
      double loaded PEGylated liposomes (DLPLs) containing PTX and PTX-DMbetaCD complex
      were prepared by thin film hydration. Physicochemical characterization of complex
      and prepared DLPLs was carried out. Cytotoxic potential, hemolytic potential and
      pharmacokinetics of DLPLs were tested in comparison to Taxol(r). Aqueous
      solubility of PTX increased by almost 3 * 104 folds due to complexation with
      DMbetaCD as compared to pure drug solubility. Liposomal system was found to have
      162.8 +/- 4.1 nm size, zeta potential of -5.6 +/- 0.14 mV and 2-fold increase in
      drug loading to 5.8 mol % for PTX due to double loading. DLPLs had low hemolytic
      potential and higher cytotoxicity on SKOV3 cells with improvement in IC50 value
      by 4.2 folds as compared to Taxol(r) at 48 h. The anti-angiogenic potential of
      DLPLs was confirmed by 1.33 folds lesser wound recovery in SKOV3 cells compared
      to Taxol(r). In-vivo pharmacokinetic evaluation of DLPLs in rats substantiates
      improvement in circulation time, higher plasma concentration and decreased
      clearance rate compared to Taxol(r). An efficacious system with improved loading
      and pharmacokinetics was formulated as potential alternative for currently
      marketed PTX formulation.

PMID- 29175441
TI  - Emotional ratings of high- and low-calorie food are differentially associated
      with cognitive restraint and dietary restriction.
AB  - Dietary restraint is a robust risk factor for binge eating and eating disorders,
      which may partially result from increased reward reactivity to food in
      individuals who attempt to diet. However, research examining the association
      between dietary restraint and reactivity to food cues is mixed. Mixed findings
      may reflect distinct relations between food cue reactivity and different
      dimensions of dietary behavior; attempts to diet (cognitive restraint) may be
      associated with increased positive evaluations of food, whereas actual reduction
      in food intake (dietary restriction) may be achieved through decreased reactivity
      to food cues. The aim of the current study was to examine whether cognitive
      restraint and dietary restriction, as assessed via subscales on a recently
      developed multidimensional measure of eating pathology (i.e., Eating Pathology
      Symptoms Inventory [EPSI]), are differentially associated with emotional
      evaluations of high- and low-calorie food. Female participants (N = 203) viewed
      12 high-calorie (i.e., sweet, savory) and 12 low-calorie (i.e., fruits,
      vegetables) food images, as well as 36 standard emotional images. Images were
      rated on the dimensions of valence, arousal, and craving using the Self
      Assessment Manikin. Cognitive restraint was correlated with greater pleasure and
      craving ratings of low-calorie, but not high-calorie, foods. In contrast, dietary
      restriction was related to reduced pleasure and craving ratings for both high-
      and low-calorie foods. Findings suggest that cognitive restraint may be
      associated with a preference for low-calorie foods; whereas dietary restriction
      may relate to reduced sensitivity to the hedonic and motivational value of food,
      regardless of caloric content. Results also provide support for the distinction
      between cognitive restraint and dietary restriction, as assessed via the EPSI.

PMID- 29175442
TI  - Transcriptome profiling provides gene resources for understanding gill immune
      responses in Japanese flounder (Paralichthys olivaceus) challenged with
      Edwardsiella tarda.
AB  - Marine organisms are commonly under threats from various pathogens. Edwardsiella
      tarda is one of the fish pathogens that seriously infect cultured and wild fish
      species. Bacteremia caused by E. tarda can be a fatal disease in humans. Fish
      gill is a mucosa-associated lymphoid tissue that directly contacted with sea
      water. Generating gill transcriptomic resources that challenged by E. tarda is
      crucial for understanding the molecular mechanisms underlying gill immune
      responses. In this study, we performed transcriptome profiling of gene expression
      in Japanese flounder gills (Paralichthys olivaceus) challenged by E. tarda with
      different stress duration. An average of 40 million clean reads per library were
      obtained, of which approximately 83.2% were successfully mapped to the reference
      genome. 456 and 1037 differential expressed genes (DEGs) were identified at 8 h
      and 48 h post-injection, respectively. Gene annotation analysis and protein
      protein interaction networks were conducted to obtain the key interaction
      relationships of immune-related DEGs during pathogens infection. 24 hub genes
      with multiple protein-protein interaction relationships or involved in multiple
      KEGG signaling pathways were discovered and validated by qRT-PCR. These hub genes
      mainly participated in Leukocyte transendothelial migration signaling pathway, B
      cell receptor signaling pathway, Wnt signaling pathway and Apoptosis signaling
      pathway. This study represents the first gill transcriptomic analysis based on
      protein-protein interaction networks in fish and provides valuable gene resources
      for understanding the fish gill immunity, which can pave the way to understand
      the molecular mechanisms of immune responses with E. tarda infection.

PMID- 29175443
TI  - Intracellular TLR22 acts as an inflammation equalizer via suppression of NF
      kappaB and selective activation of MAPK pathway in fish.
AB  - TLR22, a typical member of the fish-specific TLRs, is a crucial sensor in virally
      triggered innate immune signalling retained from natural selection. To elucidate
      the role of the TLR22-specific signalling cascade mechanism, we provide evidence
      that the double-stranded (ds) RNA-sensor TLR22 positively regulates the ERK
      pathway and negatively regulates the JNK, p38 MAP kinase and NF-kappaB pathway.
      Here, we show that TLR22 restrains NF-kappaB activation and IFN (interferon) beta
      and AP-1 (activator protein-1) promoter binding (impairing "primary response"
      genes (TNF and IL-1)), induces "secondary response" genes (IL-12 and IL-6) and
      mediates the irregular expression of inflammatory genes. Therefore, TLR22
      promotes ERK phosphorylation but impairs the JNK and p38 MAP kinases and IkappaB
      phosphorylation. Additionally, TLR22 controls the excessive generation of
      reactive oxygen species (ROS) to avoid damaging the organism. The specific
      kinetics of TLR22 depends on its distinct cellular localization. We demonstrate
      that TLR22 is an intracellular receptor localized in the endosome, and the TLR22
      TIR domain is the functional structure inducing the signalling cascade post-viral
      replication in the body. As mentioned above, our data reveal a novel mechanism
      whereby TLR22-induced positive adjustment and negative regulation evolved
      independently to avoid harmful and inappropriate inflammatory responses.

PMID- 29175444
TI  - 17beta-estradiol suppresses carboxylesterases by activating c-Jun/AP-1 pathway in
      primary human and mouse hepatocytes.
AB  - In order to study the influence of estrogen on carboxylesterases, we investigated
      the effects of 17beta-estradiol on CES1 (Ces1d) and CES2 (Ces1e) in human and
      mouse hepatocytes. After being treated with 17beta-estradiol, the mRNA levels of
      CES1 and CES2 decreased by 29-39% and 28-55%, respectively, in the human
      hepatocytes from four donors. Consistently, the hydrolysis of para
      nitrophenylacetate decreased markedly by 32% induced by 17beta-estradiol.
      Moreover, 17beta-estradiol decreased CES1 and CES2 by 45% and 47% respectively at
      protein levels. The response of altered expression of Ces1d (CES1) and Ces1e
      (CES2) to 17beta-estradiolin in mouse hepatocytes was very similar to that in the
      human hepatocytes. Further, the decreased Ces1d and Ces1e expression induced by
      17beta-estradiol could be abolished by SP600125, an inhibitor of AP-1, both at
      mRNA and protein levels. Likewise, the increased c-Jun expression induced by
      17beta-estradiol could almost be abolished by SP600125. In vivo, the expression
      of Ces1d, Ces1e and the hydrolytic activity of liver were higher in the
      ovariectomized female mice(OVX) than those in control mice(SHAM). However, when
      17beta-estradiol was administrated, the expression of Ces1d, Ces1e and the
      hydrolytic activity of liver in the ovariectomized female mice (OVX+E2) became
      restored to their normal levels. Taken together, 17beta-estradiol suppresses
      carboxylesterases by activating c-Jun/AP-1 pathway in primary human and mouse
      hepatocytes. The findings can offer the potential gains in the safety and
      efficacy of pharmacotherapy for women, especially for pregnant and menopausal
      women.

PMID- 29175445
TI  - Adipocyte biology in breast cancer: From silent bystander to active facilitator.
AB  - Adipocytes account for the largest proportion among the cells that comprise
      breast tissue; therefore, they are considered to be a critical cell type in the
      tumor microenvironment of breast cancer. In breast cancer, adipocytes are not
      only found adjacent to cancer cells, but they also play an active role in the
      entire process of cancer development, progression, metastasis, and treatment
      response. Factors including the secretion of adipokines such as leptin and
      adiponectin, as well as autotaxin, interleukin 6, tumor necrosis factor alpha,
      and hepatic growth factor, metabolic remodeling that supports the growth of
      breast cancer by transfer of fatty acids to increase mitochondrial beta
      oxidation, extracellular matrix remodeling and endotrophin production from type
      IV collagen, and cancer-associated fibroblast phenotype changes have all been
      implicated in this comprehensive process. Moreover, adipocytes may act as
      obstacles to therapy, as they are involved in mechanisms of resistance against
      various breast cancer treatments. Adipose tissues may also be a reservoir for
      dormant tumor cells during postsurgical autologous fat grafting. Thus,
      adipocytes, and the processes and pathways in which they are involved, could be
      effective therapeutic targets for breast cancer. In this review, we focus on the
      current understanding of adipocyte biology as it affects breast cancer.

PMID- 29175446
TI  - Phencyclidine increased while isolation rearing did not affect progressive ratio
      responding in rats: Investigating potential models of amotivation in
      schizophrenia.
AB  - BACKGROUND: Schizophrenia is a debilitating neurodevelopmental disorder affecting
      1% of the global population with heterogeneous symptoms including positive,
      negative, and cognitive. While treatment for positive symptoms exists, none have
      been developed to treat negative symptoms. Animal models of schizophrenia are
      required to test targeted treatments and since patients exhibit reduced effort
      (breakpoints) for reward in a progressive ratio (PR) task, we examined the PR
      breakpoints of rats treated with the NMDA receptor antagonist phencyclidine or
      those reared in isolation - two common manipulations used to induce schizophrenia
      relevant behaviors in rodents. METHODS: In two cohorts, the PR breakpoint for a
      palatable food reward was examined in Long Evans rats after: 1) a repeated
      phencyclidine regimen; 2) A subchronic phencyclidine regimen followed by drug
      washout; and 3) post-weaning social isolation. RESULTS: Rats treated with
      repeated phencyclidine and those following washout from phencyclidine exhibited
      higher PR breakpoints than vehicle-treated rats. The breakpoint of isolation
      reared rats did not differ from those socially reared, despite abnormalities of
      these rats in other schizophrenia-relevant behaviors. CONCLUSION: Despite their
      common use for modeling other schizophrenia-relevant behaviors neither
      phencyclidine treatment nor isolation rearing recreated the motivational deficits
      observed in patients with schizophrenia, as measured by PR breakpoint. Other
      manipulations, and negative symptom-relevant behaviors, require investigation
      prior to testing putative therapeutics.

PMID- 29175448
TI  - In situ investigation of bismuth nanoparticles formation by transmission electron
      microscope.
AB  - Bismuth (Bi) nanoparticles are prepared by using NaBi(MoO4)2 nanosheets in the
      beam of electrons emitted by transmission electron microscope. The formation and
      growth of Bi nanoparticles are investigated in situ. The sizes of Bi
      nanoparticles are confined within the range of 6-10nm by controlling irradiation
      time. It is also observed that once the diameter of nanoparticles is larger than
      10nm, the Bi particles are stable as a result of the immobility of large
      nanoparticles. In addition, some nanoparticles on the edges form nanorods, which
      are explained as the result of a coalescence process, if the irradiation period
      is longer than 10min. The in situ research on Bi nanoparticles facilitates in
      depth investigations of the physicochemical behavior and provides more potential
      applications in various fields such as sensors, catalysts and optical devices.

PMID- 29175447
TI  - Suppressive and enhancing effects of nicotine on food-seeking behavior.
AB  - The present study examined how systemic low doses of nicotine affect the
      microstructure of reinforced food-seeking behavior in rats. Rats were first given
      an acute saline or nicotine treatment (0.1-0.6mg/kg, with an inter-injection
      interval of at least 48h), and then a chronic saline or nicotine treatment
      (0.3mg/kg/day for 10 consecutive days). Immediately after each injection, rats
      were required to press a lever five times to obtain food that was available at
      unpredictable times (on average every 80s) with constant probability. Acute
      nicotine dose-dependently suppressed behavior prior to the delivery of the first
      reinforcer, but enhanced food-reinforced behavior afterwards. These effects were
      primarily observed in the time it took rats to initiate food-seeking behavior.
      Enhancing effects were also observed in the microstructure of food-seeking
      behavior, with lower nicotine doses (0.1-0.3mg/kg) increasing the rate at which
      response bouts were initiated, and higher doses (0.3-0.6mg/kg) increasing within
      bout response rates. A pre-feeding control suggests that changes in appetite
      alone cannot explain these effects. Over the course of chronic nicotine exposure,
      tolerance developed to the suppressive, but not to the enhancing effects of
      nicotine on food-seeking behavior. These results suggest that (a) lower doses of
      nicotine enhance the reward value of food and/or food-associated stimuli, (b)
      higher doses of nicotine enhance motoric activity, and (c) ostensive
      sensitization effects of nicotine on behavior partially reflect a tolerance to
      its transient suppressive motoric effects.

PMID- 29175449
TI  - Multiplex PCR testing for travelers' diarrhea-friend or foe?

PMID- 29175450
TI  - Crosstalk between mAChRM3 and beta2AR, via acetylcholine PI3/PKC/PBEP1/Raf-1
      MEK1/2/ERK1/2 pathway activation, in human bronchial epithelial cells after long
      term cigarette smoke exposure.
AB  - BACKGROUND: Cigarette smoke extract (CSE) affects the expression of non-neuronal
      components of cholinergic system in bronchial epithelial cells and, as PEBP1/Raf
      mediated MAPK1/2 and ERK1/2 pathway, promotes inflammation and oxidative stress.
      AIMS: We studied whether Acetylcholine (ACh) is involved in the mechanism of
      crosstalk between mAChRM3 and beta2Adrenergic receptors (beta2AR) promoting, via
      PI3/PKC/PBEP1/Raf/MEK1/2/ERK1/2 activation, beta2AR desensitization, inflammation
      and, oxidative stress in a bronchial epithelial cell line (16HBE) after long-term
      exposure to cigarette smoke extract (LECSE). METHODS: We evaluated mAChRM3 and
      Choline Acetyltransferase (ChAT) expression, ACh production, PEBP1, ERk1/2, and
      beta2AR phosphorylation, as well as NOX-4, ROS production and IL-8 release in
      16HBE after LECSE. The inhibitory activity of Hemicholinium (HCh-3) (a potent
      choline uptake blocker), LY294002 (a highly selective inhibitor of PI3 kinase),
      Tiotropium (Spiriva(r)) (anticholinergic drug) and Olodaterol (beta2AR agonist),
      were tested in 16HBE after LECSE. RESULTS: mAChRM3, ChAT, ACh activity, pPEBP1,
      pbeta2AR, pERK1/2, ROS, NOX-4 and IL-8 increased after LECSE in 16HBE LECSE
      compared to untreated cells. HCh-3 and LY294002 (alone or in combination) as well
      as Tiotropium (Spiriva(r)) or Olodaterol (alone or in combination) all reduced
      the levels of pPEBP1, pbeta2AR, pERK1/2, ROS, NOX-4, and IL-8 in 16HBE LECSE
      compared to untreated cells. CONCLUSIONS: LECSE promotes ACh production which
      enhances PI3/PKC/PEBP1/Raf-ERK1/2 pathway activation, heterologous beta2AR
      desensitization, as well as release of inflammatory and oxidative mediators in
      bronchial epithelial cells. The use of anticholinergic drugs and long-acting
      beta2-agonists, alone or in combination may be dampen these inflammatory
      mechanisms when used in combination in some epithelial cell types.

PMID- 29175451
TI  - Short-term Clinical Efficacy of Electric Pudendal Nerve Stimulation on Neurogenic
      Lower Urinary Tract Disease: A Pilot Research.
AB  - OBJECTIVE: To compare the short-term efficacy of electrical pudendal nerve
      stimulation (EPNS) vs anogenital electrical stimulation (AES) for neurogenic
      lower urinary tract disease. PATIENTS AND METHODS: Sixty eligible participants
      were randomized at a ratio of 2:1 to the test group of 40 patients and the
      control group of 20. The test group was treated with EPNS and the control group
      was treated with AES. After 12 sessions of treatment, therapeutic effects were
      evaluated based on self-assessed questionnaire scores. All patients with a
      residual urine volume >50 mL were also assessed by the post-treatment residual
      urine volume. RESULTS: At the end of treatment, the median symptom score and the
      quality of life score were 11 (range 3-23) and 4.26 (range 1.00-5.81) in the test
      group, and the median post-treatment residual urine volume was 46 (range 0-223)
      mL. By contrast, the median severity of symptoms and quality of life scores were
      15 (range 8-33) and 3.84 (range 0.89-5.84) in the control group, and the median
      post-treatment residual urine volume was 105 (range 28-340) mL. Significant
      differences between the test group and the control group could be observed in the
      post-treatment symptom score, the quality of life score, and the residual urine
      volume (with P = .005, P <.001, P = .02, respectively). CONCLUSION: Compared with
      AES, EPNS is more effective in treating neurogenic lower urinary tract disease in
      the short term.

PMID- 29175452
TI  - Changes in expression of cytokines in polyhexamethylene guanidine-induced lung
      fibrosis in mice: Comparison of bleomycin-induced lung fibrosis.
AB  - Inhalation of polyhexamethylene guanidine (PHMG) causes irreversible pulmonary
      injury, such as pulmonary fibrosis. However, the mechanism underlying PHMG
      induced lung injury is unclear. In this study, we compared the difference in time
      dependent lung injury between PHMG- and bleomycin (BLM)-treated mice and
      determined cytokines involved in inducing lung injury by performing cytokine
      antibody array analysis. Mice were treated once with 1.8mg/kg BLM or 1.2mg/kg
      PHMG through intratracheal instillation and were sacrificed on days 7 and 28.
      Bronchoalveolar lavage fluid (BALF) analysis showed that the number of
      neutrophils was significantly higher in PHMG-treated mice than in BLM-treated
      mice on day 7. Histopathological analysis showed inflammatory cell infiltration
      and fibrosis mainly in the terminal bronchioles and alveoli in the lungs of PHMG-
      and BLM-treated mice. However, continuous macrophage infiltration in the alveolar
      space and bronchioloalveolar epithelial hyperplasia (BEH) were only observed in
      PHMG-treated mice. Cytokine antibody array analysis showed that 15 and eight
      cytokines were upregulated in PHMG- and BLM-treated mice, respectively, on day 7.
      On day 28, 13 and five cytokines were upregulated in PHMG and BLM-treated mice,
      respectively. In addition, the expressed cytokines between days 7 and 28 in BLM
      treated mice were clearly different, but were similar in PHMG-treated mice.
      Consequently, between PHMG- and BLM-treated mice, we observed differences in the
      expression patterns and types of cytokines. These differences are considered to
      be a result of the inflammatory processes induced by both substances, which may
      mainly involve macrophage infiltration. Therefore, continuous induction of the
      inflammatory response by PHMG may play an important role in the development of
      pulmonary fibrosis.

PMID- 29175453
TI  - Activation of PPARalpha decreases bile acids in livers of female mice while
      maintaining bile flow and biliary bile acid excretion.
AB  - Fibrates are hypolipidemic drugs that act as activators of peroxisome
      proliferator-activated receptor alpha (PPARalpha). In both humans and rodents,
      females were reported to be less responsive to fibrates than males. Previous
      studies on fibrates and PPARalpha usually involved male mice, but little has been
      done in females. The present study aimed to provide the first comprehensive
      analysis of the effects of clofibrate (CLOF) and PPARalpha on bile acid (BA)
      homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF
      treatment increased liver weight, bile flow, and biliary BA excretion, but
      decreased total BAs in both serum and liver. In contrast, WT female mice were
      less susceptible to these CLOF-mediated responses observed in males. In WT female
      mice, CLOF decreased total BAs in the liver, but had little effect on the mRNAs
      of hepatic BA-related genes. Next, a comparative analysis between WT and
      PPARalpha-null female mice showed that lack of PPARalpha in female mice decreased
      total BAs in serum, but had little effect on total BAs in liver or bile. However,
      lack of PPARalpha in female mice increased mRNAs of BA synthetic enzymes (Cyp7a1,
      Cyp8b1, Cyp27a1, and Cyp7b1) and transporters (Ntcp, Oatp1a1, Oatp1b2, and Mrp3).
      Furthermore, the increase of Cyp7a1 in PPARalpha-null female mice was associated
      with an increase in liver Fxr-Shp-Lrh-1 signaling. In conclusion, female mice are
      resistant to CLOF-mediated effects on BA metabolism observed in males, which
      could be attributed to PPARalpha-mediated suppression in females on genes
      involved in BA synthesis and transport.

PMID- 29175455
TI  - Anxiolytic- and antidepressant-like effects of Silymarin compared to diazepam and
      fluoxetine in a mouse model of mild traumatic brain injury.
AB  - Clinical and experimental studies have shown that mild traumatic brain injury
      (mTBI) is associated with increased anxiety- and depression-related behaviors and
      inflammation in the brain. Unfortunately, there are no specific therapies for
      long-term behavioral consequences of mTBI. This study set out to determine
      whether silymarin treatment compared to diazepam (DZP) and fluoxetine (FLX) can
      reduce neuroinflammation, anxiety- and depression-like behaviors after mTBI
      induction in mice. We used open field, elevated plus maze, light-dark box, zero
      maze, sucrose preference, forced swim, and tail suspension tests to assess
      anxiety and depression-like behaviors in mTBI-induced mice. The levels of tumor
      necrosis factor (TNF)-alpha protein, a marker of inflammation, in the prefrontal
      cortex and hippocampus was also measured. This study identified that the long
      term treatment with DZP, FLX or SIL results in decreased anxiety and depression
      like behaviors in mTBI-induced mice. The results also showed that these drugs
      reduced TNF-alpha levels in the prefrontal cortex and hippocampus. In addition,
      there were no significant differences between the effects of SIL and DZP or SIL
      and FLX on behavioral and cytokine levels in mTBI-induced mice. Our findings
      support the idea that mTBI could be a risk factor for anxiety- and depression
      related disorders and neuroinflammation in the brain. Taken together, this study
      demonstrates that DZP, FLX or SIL can significantly reduce anxiety- and
      depression-like symptoms, and neuroinflammation after mTBI induction in mice.

PMID- 29175454
TI  - Selective inhibition of CTCF binding by iAs directs TET-mediated reprogramming of
      5-hydroxymethylation patterns in iAs-transformed cells.
AB  - Methylation at cytosine (5mC) is a fundamental epigenetic DNA modification
      recently associated with iAs-mediated carcinogenesis. In contrast, the role of 5
      hydroxymethylcytosine (5hmC), the oxidation product of 5mC in iAs-mediated
      carcinogenesis is unknown. Here we assess the hydroxymethylome in iAs-transformed
      cells, showing that dynamic modulation of hydroxymethylated DNA is associated
      with specific transcriptional networks. Moreover, this pathologic iAs-mediated
      carcinogenesis is characterized by a shift toward a higher hydroxymethylation
      pattern genome-wide. At specific promoters, hydroxymethylation correlated with
      increased gene expression. Furthermore, this increase in hydroxymethylation
      occurs concurrently with an upregulation of ten-eleven translocation (TET)
      enzymes that oxidize 5-methylcytosine (5mC) in DNA. To gain an understanding into
      how iAs might impact TET expression, we found that iAs inhibits the binding of
      CTCF at the proximal, weak CTCF binding sites of the TET1 and TET2 gene promoters
      and enhances CTCF binding at the stronger distal binding site. Further analyses
      suggest that this distal site acts as an enhancer, thus high CTCF occupancy at
      the enhancer region of TET1 and TET2 possibly drives their high expression in iAs
      transformed cells. These results have major implications in understanding the
      impact of differential CTCF binding, genome architecture and its consequences in
      iAs-mediated pathogenesis.

PMID- 29175456
TI  - Ecliptal, a promising natural lead isolated from Eclipta alba modulates adipocyte
      function and ameliorates metabolic syndrome.
AB  - A swift increase has been observed in the number of individuals with metabolic
      syndrome worldwide. A number of natural compounds have been identified towards
      combating metabolic syndrome. Adding to this premise, here we report the
      pleiotropic activities of Ecliptal (EC); a natural compound isolated from the
      herb Eclipta alba. Administration of EC was shown to have prominent anti
      adipogenic effects in 3T3-L1 and hMSC derived adipocytes. It was shown to
      activate Wnt-pathway and alter AKT signaling. Additionally, it caused cell cycle
      arrest and inhibited mitotic clonal expansion. EC treatment augmented
      mitochondrial biogenesis as well as function as estimated by expression of
      PGC1alpha, UCP-1, mitochondrial complexes and estimation of oxygen consumption
      rate. EC also reduced LPS-induced inflammation and tunicamycin induced ER stress.
      Further, EC enhanced insulin sensitivity by increasing AKT phosphorylation,
      inhibiting PKCalpha/betaII phosphorylation and reducing leptin/adiponectin ratio.
      Finally, EC administration in Syrian golden hamsters was shown to have potent
      anti-dyslipidemic effects. Cumulatively, encompassing pleiotropic activities of
      EC, it could prove to be a potential drug candidate against obesity, insulin
      resistance and related metabolic syndrome.

PMID- 29175457
TI  - Liposomal nanohybrid cerasomes targeted to PD-L1 enable dual-modality imaging and
      improve antitumor treatments.
AB  - Programmed death ligand-1 (PD-L1) is a central element in cancer therapies
      targeting immune checkpoints, and its expression is an important predictor of the
      therapeutic response. With recent approvals of therapeutic antibodies against PD
      L1 and PD-1, noninvasive detection methods are now urgently needed to quantify PD
      L1 expression in tumors and to evaluate the response to immune therapies.
      However, only few such methods are available. Thus, we fabricated nanohybrid
      liposomal cerasome nanoparticles loaded with the chemotherapeutic drug
      paclitaxel, and evaluated their value as a theranostic agent. The particles are
      also decorated with PD-L1 antibody to enable specific targeting, and are dual
      labeled to enable near-infrared fluorescence (NIRF) and magnetic resonance
      imaging (MRI) in vivo. Results showed that in vivo NIRF and MRI imaging following
      intravenous injection of cerasomes revealed a strong positive contrast for
      tumors, indicating long-lived enhancement of relevant signals. Moreover, the
      cerasomes were more effective against tumors and metastasis in comparison to
      simultaneous but nontargeted delivery of PD-L1 antibody and paclitaxel. Taken
      together, the data indicate that targeted, dual-labeled cerasomes are good
      theranostic agents for MRI/NIRF dual-mode detection and treatment of solid tumors
      in situ.

PMID- 29175458
TI  - TM4SF1 regulates apoptosis, cell cycle and ROS metabolism via the PPARgamma-SIRT1
      feedback loop in human bladder cancer cells.
AB  - Transmembrane-4-L-Six-Family-1 (TM4SF1) is a member of the L6 family and
      functions as a signal transducer to regulate cell development, growth and
      motility. Here we show that TM4SF1 is strongly upregulated in human muscle
      invasive bladder cancer (MIBC) tissues, corroborating the bioinformatical results
      of transcriptome analysis. Moreover, tissue microarray (TMA) shows significant
      correlations (p < 0.05) between high expression of TM4SF1 and T stage, TNM stage,
      lymph node metastasis status and survival rate of MIBC patients, indicating a
      positive association between TM4SF1 expression and poorer prognosis. Furthermore,
      in vitro and in vivo studies indicate that the proliferation of human bladder
      cancer (BCa) cells is significantly suppressed by knockdown of TM4SF1 (p < 0.05).
      Functionally, the reduction of TM4SF1 could induce cell cycle arrest and
      apoptosis possibly via the upregulation of reactive oxygen species (ROS) in BCa
      cells. In addition, these observations could be recovered by treatment with
      GW9662 (antagonist of PPARgamma) and resveratrol (activator of SIRT1). Taken
      together, our results suggest that high expression of TM4SF1 predicts poor
      prognosis of MIBC.

PMID- 29175459
TI  - PPP2R5A: A multirole protein phosphatase subunit in regulating cancer
      development.
AB  - Protein phosphatase 2, regulatory subunit B (B56), alpha isoform (PPP2R5A) is one
      of the regulatory subunits of the protein phosphatase 2A (PP2A), which is a major
      member of protein serine/threonine phosphatases in cells. PPP2R5A can regulate
      the cellular location, substrate specification and protein phosphatase function
      of PP2A, through which PPP2R5A plays an important role in many cellular
      activities. It has been reported that PPP2R5A relates with many diseases
      including some kinds of cancers, but the related mechanisms have a lot remaining
      to be discovered or demonstrated. This review arms to summarize PPP2R5A and its
      relationships with the occurrence and progression of tumors, helping us to
      further understand its significance in the prevention, early diagnosis, targeted
      therapy and prognosis improvement of tumors.

PMID- 29175460
TI  - Bad phosphorylation as a target of inhibition in oncology.
AB  - Bcl-2 agonist of cell death (BAD) is a BH3-only member of the Bcl-2 family which
      possesses important regulatory function in apoptosis. BAD has also been shown to
      possess many non-apoptotic functions closely linked to cancer including
      regulation of glycolysis, autophagy, cell cycle progression and immune system
      development. Interestingly, BAD can be either pro-apoptotic or pro-survival
      depending on the phosphorylation state of three specific serine residues (human
      S75, S99 and S118). Expression of BAD and BAD phosphorylation patterns have been
      shown to influence tumor initiation and progression and play a predictive role in
      disease prognosis, drug response and chemosensitivity in various cancers. This
      review aims to summarize the current evidence on the functional role of BAD
      phosphorylation in human cancer and evaluate the potential utility of modulating
      BAD phosphorylation in cancer.

PMID- 29175461
TI  - The future of mesenchymal stem cell-based therapeutic approaches for cancer -
      From cells to ghosts.
AB  - Mesenchymal stem cells (MSCs) are multipotent stromal cells which can
      differentiate into a variety of cell types including osteoblasts, adipocytes and
      chondrocytes. They are normally resident in adipose tissue, bone marrow and the
      umbilical cord, but can also be found in other tissues and are known to be
      recruited to sites of wound healing as well as growing tumours. The therapeutic
      potential of MSCs has been explored in a number of phase I/II and III clinical
      trials, of which several were targeted against graft-versus-host disease and to
      support engraftment of haematopoietic stem cells (HSCs), but currently only very
      few in the oncology field. There are now three clinical trials either ongoing or
      recruiting patients that use MSCs to treat tumour disease. In these, MSCs target
      gastrointestinal, lung and ovarian cancer, respectively. The first study uses
      MSCs loaded with a HSV-TK expression construct under the control of the CCL5
      promoter, and has recently reported successful completion of Phase I/II. While no
      adverse side effects were seen during this study, no outcomes with respect to
      therapeutic benefits have been published. The other clinical trials targeting
      lung and ovarian cancer will be using MSCs expressing cytokines as therapeutic
      payload. Despite these encouraging early steps towards their clinical use, many
      questions are still unanswered regarding the biology of MSCs in normal and
      pathophysiological settings. In this review, in addition to summarising the
      current state of MSC-based therapeutic approaches for cancer, we will describe
      the remaining questions, obstacles and risks, as well as novel developments such
      as MSC-derived nanoghosts.

PMID- 29175462
TI  - Metabolic adaptation of macrophages in chronic diseases.
AB  - In response to physiological and pathological stimuli, macrophages are able to
      adapt and shape their phenotype, giving rise to a broad range of functional
      activation that is unique in different organs and different pathologies. The
      plasticity of macrophages is accomplished not only by di stinct signalling
      pathways and transcriptional profiles but also by specific engagement of
      preferential metabolic pathways. In the last decade, macrophage metabolism became
      the object of multiple studies showing that, by altering nutrient availability or
      by blocking specific metabolic pathway it is possible to skew macrophage
      phenotype and alter their effector functions. This field of research opens new
      therapeutic windows for the cure of several disease. Here we will give an
      overview of the current knowledge of macrophage metabolism in cancer,
      atherosclerosis and obesity and how this knowledge could be translated in
      therapeutic opportunities.

PMID- 29175463
TI  - Increasing methamphetamine injection among non-MSM who inject drugs in King
      County, Washington.
AB  - BACKGROUND: In King County, Washington, the HIV prevalence among men who have sex
      with men (MSM) who inject methamphetamine is high, while it is low among other
      people who inject drugs (PWID). Local drug problem indicators suggest that
      methamphetamine use is increasing. The extent to which this increase affects MSM
      and non-MSM, and whether MSM and non-MSM networks are connected through injection
      equipment sharing, is unknown. METHODS: We used data from two serial cross
      sectional surveys of PWID including five biannual surveys of Public Health
      Seattle and King County Needle and Syringe Exchange Program clients (NSEP,
      N=2135, 2009-2017) and three National HIV Behavioral Surveillance IDU surveys
      (NHBS, N=1709, 2009-2015). RESULTS: The proportion of non-MSM PWID reporting any
      recent methamphetamine injection increased significantly from approximately 20%
      in 2009 to 65% in 2017. Most of this increase was attributable to injecting
      methamphetamine in combination with heroin (goofballs). PWID who injected
      goofballs were more likely to be younger, homeless or unstably housed, report
      daily injection, and self-report an opioid overdose in the past year than other
      PWID. The majority of PWID who injected methamphetamine reported sharing any
      injection equipment. Among these PWID, 43% of MSM had last shared injection
      equipment with a non-MSM. Eight percent of non-MSM men and 15% of women had last
      shared equipment with an MSM. CONCLUSIONS: Given non-trivial rates of sharing
      injection equipment with methamphetamine-using MSM, a population with an HIV
      prevalence of 40%, non-MSM who inject methamphetamine could be an emerging
      population at risk for acquiring HIV.

PMID- 29175464
TI  - Salience network coupling is linked to both tobacco smoking and symptoms of
      attention deficit hyperactivity disorder (ADHD).
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) symptoms, even
      those below diagnostic threshold, enhance the likelihood of nicotine dependence,
      suggesting a neurobiological link between disorders. Of particular interest is
      the salience network (SN), which mediates attention to salient internal/external
      stimuli to guide behavior and is anchored by the dorsal anterior cingulate cortex
      (dACC) and bilateral anterior insula (AI). Disrupted interactions between the SN
      and the default mode (DMN) and central executive networks (CEN) have been noted
      in both ADHD and nicotine dependence. Further, enhanced intra-SN coupling between
      the dACC-AI influences aspects of nicotine dependence such as reactivity to
      smoking cues. METHODS: To identify links between SN functional connectivity and
      ADHD symptoms in nicotine dependence, we compared 21 nicotine dependent
      individuals with 17 non-smokers on ADHD symptoms as measured by the ADHD self
      report scale (ASRS) and resting state intra and inter-SN functional connectivity.
      RESULTS: Relative to healthy controls, nicotine dependent individuals had
      significantly higher ASRS scores and greater dACC-AI coupling. No group
      differences were noted on inter-SN network coupling. A significant association
      was found between ASRS and dACC-AI coupling both in the entire cohort and
      specifically when evaluating nicotine dependent individuals alone. CONCLUSIONS:
      The greater ASRS scores in nicotine dependent individuals is in line with
      existent literature and the stronger dACC-AI coupling in smokers further supports
      the role of this network in nicotine dependence. The significant association
      between dACC-AI coupling and ASRS suggests that intra-SN coupling strength may
      impact neurocognitive functioning associated with both ADHD symptoms and nicotine
      dependence.

PMID- 29175465
TI  - Effect of photodynamic and laser therapy in the treatment of peri-implant
      mucositis: A systematic review.
AB  - BACKGROUND: The present study systematically reviewed the literature to
      investigate the effect of photodynamic therapy (PDT) or laser therapy (LT) in the
      management of peri-implant mucositis (p-iM). METHODS: The electronic databases
      were searched until October 2017. Outcome measures were bleeding on probing
      (BOP), plaque index (PI), or probing depth (PD). The addressed PICO question was:
      "Is PDT and LT effective in the management of p-iM?" RESULTS: A total of five
      studies included in the qualitative analysis, two of which had a low risk of
      bias. Three studies used PDT while two studies used LT. All studies reported a
      significant improvement in clinical peri-implant inflammatory parameters in p-iM.
      For PDT, one study demonstrated a significant reduction for PDT group as compared
      to manual debridement (MD), while one study indicated comparable outcomes when
      tested with probiotics at follow-up. One study used PDT alone and indicated
      significant improvements in peri-implant parameters at follow-up. However, in the
      studies using LT, one study demonstrated a significant improvement in peri
      implant parameters as compared to scaling and root planing alone, while other
      study indicated comparable outcomes when compared with manual
      debridement/chlorhexidine group at follow-up. CONCLUSION: This systematic review
      demonstrated inconclusive findings to show the effect of PDT or LT in the
      management of p-iM due to methodological heterogeneity such as non-standard
      control groups, laser parameters and short follow-up period. The results of this
      review should be considered preliminary and further, more robust, well-designed
      studies with long-term follow up and standardized comparators with laser
      parameters are warranted.

PMID- 29175466
TI  - Photodynamic therapy for treatment of oral mucositis: Pilot study with pediatric
      patients undergoing chemotherapy.
AB  - BACKGROUND: Oral mucositis has become a major dose-limiting toxicity of
      antineoplastic treatment. AIM: The aim of this study was to evaluate the effect
      of photodynamic therapy (PDT) and low level laser therapy (LLLT) on the treatment
      of chemotherapy-induced mucositis in pediatric patients. METHODS: An open,
      controlled, and blind, randomized clinical trial was conducted with 29 patients,
      from 10 months to 18 years old, who were divided into two groups. Group A was
      submitted to photodynamic therapy (0.01% Methylene Blue and red laser, lambda660
      nm) with 3J energy per point; and Group B submitted to low level laser therapy
      (lambda660 nm) with 1J energy per point. The results were evaluated by using the
      WHO and ChIMES mucositis scales. The Chi-square, Exact Fisher, Student's-t and
      Mann-Whitney tests, and the mixed linear regression model were used for
      comparison between the groups, with the maximum error admitted of 5%. RESULTS:
      There was no difference between the groups as regards the number of sessions
      necessary for clinical cure of the oral lesions (p = 0.954) or reduction in pain
      reported by the patients (p = 0.258; p = 0.486). Within each group, however,
      there was significant reduction in pain (p = 0.032; p = 0.003). The number needed
      to treat (NNT) was 4.75. CONCLUSIONS: PDT or LLLT could be used for treatment of
      oral mucositis in children/young patients. Each were well tolerated and presented
      satisfactory results in reducing pain associated with the lesion.

PMID- 29175467
TI  - Synthesis, in vitro and in vivo evaluation of 18F-fluoronorimatinib as
      radiotracer for Imatinib-sensitive gastrointestinal stromal tumors.
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GIST) have a wide range of
      mutations, but can mostly be treated with Imatinib, until eventually resistance
      towards this tyrosine kinase inhibitor is acquired. Early and non-invasive
      determination of the sensitivity of the tumor and its metastases towards Imatinib
      by positron emission tomography (PET) would be beneficial for therapy planning
      and monitoring. METHODS: We developed a synthesis strategy towards the precursor
      molecule, performed the 18F-synthesis and in the following evaluated the
      radioligand in vitro regarding its lipophilicity, stability and biological
      activity (KIT binding properties) as well as its in vivo properties in GIST tumor
      bearing mice. RESULTS: [18F]fluoronorimatinib could be obtained in an overall
      radiochemical yield of 22.2+/-3.3% within 90min. The radioligand showed high GIST
      cell uptake and was able to distinguish between Imatinib-sensitive and resistant
      tumor cell lines (GIST-T1, GIST882, GIST430) in vitro. Further biological
      evaluations of the ligand towards 9 different GIST-relevant KIT mutations showed
      comparable binding affinities compared to the structural lead Norimatinib (65nM
      vs. 53nM for wt-KIT). The in vivo evaluation of the newly developed radioligand
      showed tumor-to-background-ratios comparable to previously described, similar
      radiotracers. CONCLUSIONS: Thus, [18F]fluoronorimatinib is able to distinguish
      between Imatinib-resistant and sensitive KIT mutations. Although no improvement
      of in vivo tumor-to-background ratios could be achieved compared to formerly
      described radioligands, the hepatic uptake could be considerably reduced, being
      advantageous for the imaging of GIST. Advances in knowledge and implications for
      patient care: We were able to show that it is possible to significantly reduce
      the unfavorably high hepatic uptake of small-molecule radioligands applicable for
      GIST PET imaging. This work can thus be the basis for further work intending to
      develop a PET-radioligand for Imatinib-dependent GIST imaging.

PMID- 29175468
TI  - Difficulties in Pain Management Using Oxycodone and Fentanyl in Enzalutamide
      Treated Patients With Advanced Prostate Cancer.

PMID- 29175469
TI  - Histogram based analysis of lung perfusion of children after congenital
      diaphragmatic hernia repair.
AB  - OBJECTIVES: To investigate a histogram based approach to characterize the
      distribution of perfusion in the whole left and right lung by descriptive
      statistics and to show how histograms could be used to visually explore perfusion
      defects in two year old children after Congenital Diaphragmatic Hernia (CDH)
      repair. METHODS: 28 children (age of 24.2+/-1.7months; all left sided hernia; 9
      after extracorporeal membrane oxygenation therapy) underwent quantitative DCE-MRI
      of the lung. Segmentations of left and right lung were manually drawn to mask the
      calculated pulmonary blood flow maps and then to derive histograms for each lung
      side. Individual and group wise analysis of histograms of left and right lung was
      performed. RESULTS: Ipsilateral and contralateral lung show significant
      difference in shape and descriptive statistics derived from the histogram
      (Wilcoxon signed-rank test, p<0.05) on group wise and individual level. Subgroup
      analysis (patients with vs without ECMO therapy) showed no significant
      differences using histogram derived parameters. CONCLUSIONS: Histogram analysis
      can be a valuable tool to characterize and visualize whole lung perfusion of
      children after CDH repair. It allows for several possibilities to analyze the
      data, either describing the perfusion differences between the right and left lung
      but also to explore and visualize localized perfusion patterns in the 3D lung
      volume. Subgroup analysis will be possible given sufficient sample sizes.

PMID- 29175470
TI  - A comparison of readout segmented EPI and interleaved EPI in high-resolution
      diffusion weighted imaging.
AB  - PURPOSE: To provide a comprehensive understanding of multi-shot EPI diffusion
      imaging methods by comparing Readout segmented EPI (RS-EPI) and interleaved EPI
      (iEPI). MATERIALS AND METHODS: RS-EPI and iEPI were compared on the same 3T
      scanner. A 2D navigator was used for both RS-EPI and iEPI for phase correction.
      Signal to noise ratio (SNR), fractional anisotropy (FA) and distortion level were
      compared using phantom data. Distortion reduction capability and scan efficiency
      were compared with different protocols with simulations. In addition, distortion
      reduction capability and diffusion tensor imaging performance were compared using
      in vivo data. RESULTS: Our phantom data showed that the mean SNRs were 50.5, 86.6
      and 45.4 for RS-EPI using GRAPPA=3, fully sampled iEPI and iEPI using GRAPPA=2
      respectively. The mean FA values were 0.08, 0.05 and 0.09 for RS-EPI using
      GRAPPA=3, fully sampled iEPI and iEPI using GRAPPA=2 respectively. The distortion
      levels were 1.34mm, 1.29mm and 0.61mm for RS-EPI using GRAPPA=3, fully sampled
      iEPI and iEPI using GRAPPA=2 respectively. The effective echo spacing could be
      reduced by increasing the number of shots for both methods but more prominent for
      iEPI. The scan time was approximately proportional to the number of shots for
      both methods and RS-EPI showed a shorter scan time. Our in vivo data for
      distortion comparison showed consistent results with the effective echo spacing
      study. The mean difference of the FA and MD values between the high resolution
      sequences and SS-EPI was all within 7%. CONCLUSION: For high resolution diffusion
      imaging, iEPI has more potential in distortion reduction than RS-EPI when
      increasing the number of shots. RS-EPI can achieve a reasonable SNR with a
      shorter scan time than iEPI. RS-EPI and iEPI have similar performance in FA and
      MD quantifications as well as showing structure details when using eleven shots
      for in vivo diffusion tensor imaging.

PMID- 29175471
TI  - Deletion of mstna and mstnb impairs the immune system and affects growth
      performance in zebrafish.
AB  - Myostatin (Mstn) is a negative regulator of muscle development in vertebrates.
      Although its function in muscle growth has been well studied in mammals and fish,
      it remains unclear whether or how mstn functions in the immune system. In this
      study, mstna-/- and mstnb-/- homozygous zebrafish were firstly generated using
      CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR
      associated protein 9). Deletion of mstnb but not mstna enhanced growth
      performance. Although survival rates under normal conditions were slightly
      decreased in both strains, mortality after dexamethasone-induced stress was
      increased by ~30%. Furthermore, transcriptional levels of several critical immune
      related genes were decreased, and the ability to withstand exposure to pathogenic
      E. tarda was decreased, compared with that of controls. In mstnb-/- but not mstna
      /- zebrafish, expression of NF-kappaB subunits and several pro-inflammatory
      cytokines failed to respond to E. tarda exposure except nfkb1, c-rel and
      tnfalpha. Taken together, these results indicate that mstnb but not mstna plays a
      key role in zebrafish muscle growth. While each paralogue contributes to the
      response to bacterial insult, mstnb affects the immune system through activation
      of the NF-kappaB pathway, and mstna is likely to act upstream of NF-kappaB at
      some as yet unidentified target.

PMID- 29175472
TI  - Vaccination and immune responses of European sea bass (Dicentrarchus labrax L.)
      against betanodavirus.
AB  - This review summarizes the available knowledge on the immune defences of European
      sea bass against antigenic preparations derived from the viral encephalopathy and
      retinopathy virus (betanodavirus), which represents a major threat to the health
      of this fish species. The nodavirus is widely present and differentiates into
      several strains that infect invertebrates (in insects, alphanodavirus) and
      teleost fish, and thus may represent a great problem for farmed fish species.
      Many efforts have been directed to discovering new immunizations to induce
      protection in sea bass, especially at young stages, and these efforts have
      included employing diverse betanodavirus strains, antigen preparation,
      vaccination routes, and the addition of adjuvants and/or immunostimulants. The
      obtained results showed that inactivated preparations of betanodavirus that were
      administered intraperitoneally may induce both immune recognition and protection.
      Attempts at performing mucosal immunization by immersion and/or oral
      administration, which is a vaccination route that is highly preferred for sea
      bass, have shown intriguing results, and more studies are necessary for its
      improvement. Overall, the objective of identifying a reliable vaccine that also
      cross-protects against different genotypes or reassortant viruses for use in
      European sea bass against betanodavirus appears to be an attainable goal in the
      near future.

PMID- 29175473
TI  - Mechanisms underlying the heterogeneity of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) disorders in
      which recurrent chromosome abnormalities and gene mutations define a clonal
      hematopoiesis. The MDS-initiating cell is a rare HSC which transmits the genetic
      abnormalities to its myeloid and lymphoid progeny. The heterogeneity of MDS
      phenotypes could be linked to the diversity of genetic events involving
      epigenetic regulators, chromatin modifiers, splicing factors, transcription
      factors and signaling adaptors, the various combinations and order of mutations
      in cooperating genes, and the variegation of clonal hematopoietic hierarchy.
      Usually, epigenetic and splicing gene mutations occur first. A combination of one
      epigenetic event with a splicing gene alteration is frequent. The HSC compartment
      is invaded by a dominant and few minor clones organized linearly or with a
      branched architecture. The dominant clone containing the first initiating
      mutations produces myeloid and lymphoid lineages in transplanted immune-deficient
      mice. The mutations confer a selective advantage to myeloid progenitors at the
      expense of lymphoid progenitors. In the context of differentiation, one mutation
      may favor the amplification of granulo-monocytic progenitor, which drives the
      transformation into acute myeloid leukemia. Understanding the hierarchy of
      mutations provides insights on the mechanism of transformation. Investigation of
      mutation pattern and distribution along the hematopoietic tree may influence the
      therapeutic decision for targeted therapy.

PMID- 29175474
TI  - Enhanced H3K4me3 modifications are involved in the transactivation of DNA damage
      responsive genes in workers exposed to low-level benzene.
AB  - In this study, we explore whether altered global histone modifications respond to
      low-level benzene exposure as well as their association with the hematotoxicity.
      We recruited 147 low-level benzene-exposed workers and 122 control workers from a
      petrochemical factory in Maoming City, Guangdong Province, China. The internal
      exposure marker level, urinary S-phenylmercapturic acid (SPMA), in benzene
      exposed workers was 1.81-fold higher than that of the controls (P < 0.001). ELISA
      method was established to examine the specific histone modifications in human
      peripheral blood lymphocytes (PBLCs) of workers. A decrease in the counts of
      white blood cells (WBC), neutrophils, lymphocytes, and monocytes appeared in the
      benzene-exposed group (all P < 0.05) compared to the control group. Global
      trimethylated histone 3 lysine 4 (H3K4me3) modification was enhanced in the
      benzene-exposed group (P < 0.05) and was positively associated with the
      concentration of urinary SPMA (beta = 0.103, P = 0.045) and the extent of DNA
      damage (% Tail DNA: beta = 0.181, P = 0.022), but was negatively associated with
      the leukocyte count (WBC: beta = -0.038, P = 0.023). The in vitro study revealed
      that H3K4me3 mark was enriched in the promoters of several DNA damage responsive
      (DDR) genes including CRY1, ERCC2, and TP53 in primary human lymphocytes treated
      with hydroquinone. Particularly, H3K4me3 modification was positively correlated
      with the expression of CRY1 in the PBLCs of benzene-exposed workers. These
      observations indicate that H3K4me3 modification might mediate the transcriptional
      regulation of DDR genes in response to low-dose benzene exposure.

PMID- 29175475
TI  - Elevated ozone affects C, N and P ecological stoichiometry and nutrient
      resorption of two poplar clones.
AB  - The effects of elevated ozone on C (carbon), N (nitrogen) and P (phosphorus)
      ecological stoichiometry and nutrient resorption in different organs including
      leaves, stems and roots were investigated in poplar clones 546 (P. deltoides cv.
      '55/56' * P. deltoides cv. 'Imperial') and 107 (P. euramericana cv. '74/76') with
      a different sensitivity to ozone. Plants were exposed to two ozone treatments, NF
      (non-filtered ambient air) and NF60 (NF with targeted ozone addition of 60 ppb),
      for 96 days in open top chambers (OTCs). Significant ozone effects on most
      variables of C, N and P ecological stoichiometry were found except for the C
      concentration and the N/P in different organs. Elevated ozone increased both N
      and P concentrations of individual organs while for C/N and C/P ratios a
      reduction was observed. On these variables, ozone had a greater effect for clone
      546 than for clone 107. N concentrations of different leaf positions ranked in
      the order upper > middle > lower, showing that N was transferred from the lower
      senescent leaves to the upper ones. This was also indicative of N resorption
      processes, which increased under elevated ozone. N resorption of clone 546 was 4
      times larger than that of clone 107 under ambient air (NF). However, elevated
      ozone (NF60) had no significant effect on P resorption for both poplar clones,
      suggesting that their growth was only limited by N, while available P in the soil
      was enough to sustain growth. Understanding ecological stoichiometric responses
      under ozone stress is crucial to predict future effects on ecological processes
      and biogeochemical cycles.

PMID- 29175476
TI  - Source apportionment of aerosol particles at a European air pollution hot spot
      using particle number size distributions and chemical composition.
AB  - Ostrava in the Moravian-Silesian region (Czech Republic) is a European air
      pollution hot spot for airborne particulate matter (PM), polycyclic aromatic
      hydrocarbons (PAHs), and ultrafine particles (UFPs). Air pollution source
      apportionment is essential for implementation of successful abatement strategies.
      UFPs or nanoparticles of diameter <100 nm exhibit the highest deposition
      efficiency in human lungs. To permit apportionment of PM sources at the hot-spot
      including nanoparticles, Positive Matrix Factorization (PMF) was applied to
      highly time resolved particle number size distributions (NSD, 14 nm-10 MUm) and
      PM0.09-1.15 chemical composition. Diurnal patterns, meteorological variables,
      gaseous pollutants, organic markers, and associations between the NSD factors and
      chemical composition factors were used to identify the pollution sources. The PMF
      on the NSD reveals two factors in the ultrafine size range: industrial UFPs (28%,
      number mode diameter - NMD 45 nm), industrial/fresh road traffic nanoparticles
      (26%, NMD 26 nm); three factors in the accumulation size range: urban background
      (24%, NMD 93 nm), coal burning (14%, volume mode diameter - VMD 0.5 MUm),
      regional pollution (3%, VMD 0.8 MUm) and one factor in the coarse size range:
      industrial coarse particles/road dust (2%, VMD 5 MUm). The PMF analysis of PM0.09
      1.15 revealed four factors: SIA/CC/BB (52%), road dust (18%), sinter/steel (16%),
      iron production (16%). The factors in the ultrafine size range resolved with NSD
      have a positive correlation with sinter/steel production and iron production
      factors resolved with chemical composition. Coal combustion factor resolved with
      NSD has moderate correlation with SIA/CC/BB factor. The organic markers
      homohopanes correlate with coal combustion and the levoglucosan correlates with
      urban background. The PMF applications to NSD and chemical composition datasets
      are complementary. PAHs in PM1 were found to be associated with coal combustion
      factor.

PMID- 29175477
TI  - Surface O3 photochemistry over the South China Sea: Application of a near
      explicit chemical mechanism box model.
AB  - A systematic field measurement was conducted at an island site (Wanshan Island,
      WSI) over the South China Sea (SCS) in autumn 2013. It was observed that mixing
      ratios of O3 and its precursors (such as volatile organic compounds (VOCs),
      nitrogen oxides (NOx = NO + NO2) and carbon monoxide (CO)) showed significant
      differences on non-episode days and episode days. Additional knowledge was gained
      when a photochemical box model incorporating the Master Chemical Mechanism (PBM
      MCM) was applied to further investigate the differences/similarities of O3
      photochemistry between non-episode and episode days, in terms of O3-precursor
      relationship, atmospheric photochemical reactivity and O3 production. The
      simulation results revealed that, from non-O3 episode days to episode days, 1) O3
      production changed from both VOC and NOx-limited (transition regime) to VOC
      limited; 2) OH radicals increased and photochemical reaction cycling processes
      accelerated; and 3) both O3 production and destruction rates increased
      significantly, resulting in an elevated net O3 production over the SCS. The
      findings indicate the complexity of O3 pollution over the SCS.

PMID- 29175478
TI  - Qualitative assessment to determine internal and external factors influencing the
      origin of styrene oligomers pollution by polystyrene plastic in coastal marine
      environments.
AB  - The objective of this study is to investigate the qualitative contribution of
      internal and external factors of the area contaminated by polystyrene (PS) in
      coastal marine environments. This study is based on the extensive results of
      monitoring the styrene oligomers (SOs) present in sand and seawater samples along
      various coastlines of the Pacific Ocean. Here, anthropogenic SOs is derived from
      PS during manufacture and use, and can provide clues about the origin of SOs by
      PS pollution. The monitoring results showed that, if the concentration of SOs in
      water is higher than those concentrations in beach sand, this area could be
      affected by PS plastic caused by an external factor. On the other hand, if the
      concentration of SOs is higher in the beach sand, the region can be mainly
      influenced by PS plastic derived from its own area. Unlike the case of an
      external factor, in this case (internal influence), it is possible to take policy
      measures of the area itself for the PS plastic problem. Thus, this study is
      motivated by the need of policy measures to establish a specific alternative to
      the problems of PS plastic pollution in ocean environments.

PMID- 29175479
TI  - Methane emissions from a landfill in north-east India: Performance of various
      landfill gas emission models.
AB  - Rapid urbanization and economic growth has led to significant increase in
      municipal solid waste generation in India during the last few decades and its
      management has become a major issue because of poor waste management practices.
      Solid waste generated is deposited into open dumping sites with hardly any
      segregation and processing. Carbon dioxide (CO2), methane (CH4) and nitrous oxide
      (N2O) are the major greenhouse gases that are released from the landfill sites
      due to the biodegradation of organic matter. In this present study, CH4 and CO2
      emissions from a landfill in north-east India are estimated using a flux chamber
      during September, 2015 to August, 2016. The average emission rates of CH4 and CO2
      are 68 and 92 mg/min/m2, respectively. The emissions are highest in the summer
      whilst being lowest in winter. The diurnal variation of emissions indicated that
      the emissions follow a trend similar to temperature in all the seasons.
      Correlation coefficients of CH4 and temperature in summer, monsoon and winter are
      0.99, 0.87 and 0.97, respectively. The measured CH4 in this study is in the range
      of other studies around the world. Modified Triangular Method (MTM), IPCC model
      and the USEPA Landfill gas emissions model (LandGEM) were used to predict the CH4
      emissions during the study year. The consequent simulation results indicate that
      the MTM, LandGEM-Clean Air Act, LandGEM-Inventory and IPCC models predict 1.9,
      3.3, 1.6 and 1.4 times of the measured CH4 emission flux in this study. Assuming
      that this higher prediction of CH4 levels observed in this study holds well for
      other landfills in this region, a new CH4 emission inventory (Units:
      Tonnes/year), with a resolution of 0.10 * 0.10 has been developed. This study
      stresses the importance of biodegradable composition of waste and meteorology,
      and also points out the drawbacks of the widely used landfill emission models.

PMID- 29175481
TI  - Purification, characterization and biological effect of lectin from the marine
      sponge Stylissa flexibilis (Levi, 1961).
AB  - SFL, a lectin from the marine sponge Stylissa flexibilis was purified by cold
      ethanol precipitation followed by ion exchange chromatography on DEAE Sepharose
      column and Sephacryl S-200 gel filtration. SFL is a dimeric glycoprotein of 32kDa
      subunits linked by a disulfide bridge with a molecular mass of 64kDa by SDS-PAGE
      and 65kDa by Sephacryl S-200 gel filtration. SFL preferentially agglutinated
      enzyme treated human A erythrocytes. The activity of lectin was strongly
      inhibited by monosaccharide d-galactose and glycoproteins asialo-porcine stomach
      mucin and asialo-fetuin. The lectin was Ca2+ dependent, stable over a range of pH
      from 5 to 8, and up to 60 degrees C for 30min. The N-terminal amino acid sequence
      of SFL was also determined and a blast search on amino acid sequences revealed
      that the protein showed similarity only with lectins from the marine sponge
      Spheciospongia vesparia. SFL caused agglutination of Vibrio alginolyticus and V.
      parahaemolyticus in a dose dependent manner and inhibited the growth rates of the
      virulent bacterial strains. Growth inhibition of V. alginolyticus and V.
      parahaemolyticus with SFL was not observed in the presence of d-galactose or
      asialo-porcine stomach mucin, suggesting that the lectin caused the agglutination
      through binding to the target receptor(s) on the surface of Vibrios. Thus, the
      marine sponge S. flexibilis could promise to be a good source of a lectin(s) that
      may be useful as a carbohydrate probe and an antibacterial reagent.

PMID- 29175482
TI  - Impacts of wastewater treatment plant effluent on energetics and stress response
      of rainbow darter (Etheostoma caeruleum) in the Grand River watershed.
AB  - The objective of this study was to assess the effects of municipal wastewater
      treatment plant effluent on the energetics and stress response of rainbow darter
      (Etheostoma caeruleum). Male and female rainbow darter were collected upstream
      and downstream of the Waterloo WWTP in the Grand River watershed, ON, Canada. To
      assess the effects of wastewater treatment plant effluent on whole-body and
      tissue specific metabolic capacity, closed-chamber respirometry and muscle-enzyme
      activity analyses were performed. Plasma cortisol was also collected from fish
      before and after an acute air-exposure stressor to evaluate the cortisol stress
      response in fish exposed to additional stressors. Male and female rainbow darter
      collected downstream of the effluent had higher oxygen consumption rates, while
      differences in enzyme activities were primarily associated with sex rather than
      collection site. No impairment in the cortisol stress response between downstream
      and upstream fish was observed, however baseline cortisol levels in female fish
      from the downstream site were significantly higher compared to other baseline
      groups. Stress-induced cortisol levels were also higher in female fish from both
      sites when compared to their male counterparts. Overall, this study demonstrates
      that chronic exposure to WWTP effluent impacts whole-body metabolic performance.
      This study was also able to demonstrate that sex-differences are a key
      determinant of various metabolic changes in response to physiological stress,
      thereby, providing a novel avenue to be considered and further explored.

PMID- 29175484
TI  - Effects of hypoxia at different life stages on locomotory muscle phenotype in
      deer mice native to high altitudes.
AB  - Animals native to high altitude must overcome the constraining effects of hypoxia
      on tissue O2 supply to support routine metabolism, thermoregulation in the cold,
      and exercise. Deer mice (Peromyscus maniculatus) native to high altitude have
      evolved an enhanced aerobic capacity in hypoxia, along with increased capillarity
      and oxidative capacity of locomotory muscle. Here, we examined whether exposure
      to chronic hypoxia during development or adulthood affects muscle phenotype. Deer
      mice from a highland population were bred in captivity at sea level, and exposed
      to normoxia or one of four treatments of hypobaric hypoxia (12kPa O2, simulating
      hypoxia at ~4300m): adult hypoxia (6-8weeks), post-natal hypoxia (birth to
      adulthood), pre-natal hypoxia (before conception to adulthood), and parental
      hypoxia (in which mice were conceived and raised in normoxia, but their parents
      were previously exposed to hypoxia). Litter size was similar across treatments,
      and pups survived the hypoxia exposures and grew to similar body masses at ~6
      8months of age. Hypoxia had no effect on the masses of gastrocnemius and soleus
      muscles. There was a strong concordance between two distinct histological methods
      for staining capillaries in the gastrocnemius - alkaline phosphatase activity and
      binding of Griffonia simplicifolia lectin I - each of which showed that
      capillarity and muscle fibre size were largely unaffected by hypoxia. Maximal
      activities of several metabolic enzymes (cytochrome c oxidase, citrate synthase,
      isocitrate dehydrogenase, and lactate dehydrogenase) in the gastrocnemius were
      also largely unaffected by hypoxia. Therefore, the evolved muscle phenotype of
      high-altitude deer mice is relatively insensitive to hypoxia across life stages.

PMID- 29175480
TI  - Diagnostic imaging in the management of patients with metabolic syndrome.
AB  - Metabolic syndrome (MetS) is the constellation of metabolic risk factors that
      might foster development of type 2 diabetes and cardiovascular disease. Abdominal
      obesity and insulin resistance play a prominent role among all metabolic traits
      of MetS. Because intervention including weight loss can reduce these morbidity
      and mortality in MetS, early detection of the severity and complications of MetS
      could be useful. Recent advances in imaging modalities have provided significant
      insight into the development and progression of abdominal obesity and insulin
      resistance, as well as target organ injuries. The purpose of this review is to
      summarize advances in diagnostic imaging modalities in MetS that can be applied
      for evaluating each components and target organs. This may help in early
      detection, monitoring target organ injury, and in turn developing novel
      therapeutic target to alleviate and avert them.

PMID- 29175485
TI  - Short- and Long-term Exposure to Low and High Dose Running Produce Differential
      Effects on Hippocampal Neurogenesis.
AB  - Continuous running wheel (RW) exercise increases adult hippocampal neurogenesis
      in the dentate gyrus (DG) of rodents. Evidence suggests that greater amounts of
      RW exercise does not always equate to more adult-generated neurons in
      hippocampus. It can also be argued that continuous access to a RW results in
      exercise levels not representative of human exercise patterns. This study tested
      if RW paradigms that more closely represent human exercise patterns (e.g. shorter
      bouts, alternating daily exercise) alter neurogenesis. Neurogenesis was measured
      by examining the survival and fate of bromodeoxyuridine (BrdU)-labeled
      proliferating cells in the DG of male Sprague-Dawley rats after acute (14 days)
      or chronic (30 days) RW access. Rats were assigned to experimental groups based
      on the number of hours that they had access to a RW over two days: 0 h, 4 h, 8 h,
      24 h, and 48 h. After acute RW access, rats that had unlimited access to the RW
      on alternating days (24 h) had a stronger neurogenic response compared to those
      rats that ran modest distances (4 h, 8 h) or not at all (0 h). In contrast,
      following chronic RW access, rats that ran a moderate amount (4 h, 8 h) had
      significantly more surviving cells compared to 0 h, 24 h, and 48 h. Linear
      regression analysis established a negative relationship between running distance
      and surviving BrdU+ cells in the chronic RW access cohort (R2 = 0.40). These data
      demonstrate that in rats moderate amounts of RW exercise are superior to
      continuous daily RW exercise paradigms at promoting hippocampal neurogenesis in
      the long-term.

PMID- 29175483
TI  - The effects of dietary beta-guanidinopropionic acid on growth and muscle fiber
      development in juvenile red porgy, Pagrus pagrus.
AB  - beta-guanidinopropionic acid (beta-GPA) has been used in mammalian models to
      reduce intracellular phosphocreatine (PCr) concentration, which in turn lowers
      the energetic state of cells. This leads to changes in signaling pathways that
      attempt to re-establish energetic homeostasis. Changes in those pathways elicit
      effects similar to those of exercise such as changes in body and muscle growth,
      metabolism, endurance and health. Generally, exercise effects are beneficial to
      fish health and aquaculture, but inducing exercise in fishes can be impractical.
      Therefore, this study evaluated the potential use of supplemental beta-GPA to
      induce exercise-like effects in a rapidly growing juvenile teleost, the red porgy
      (Pagrus pagrus). We demonstrate for the first time that beta-GPA can be
      transported into teleost muscle fibers and is phosphorylated, and that this
      perturbs the intracellular energetic state of the cells, although to a lesser
      degree than typically seen in mammals. beta-GPA did not affect whole animal
      growth, nor did it influence skeletal muscle fiber size or myonuclear
      recruitment. There was, however, an increase in mitochondrial volume within
      myofibers in treated fish. GC/MS metabolomic analysis revealed shifts in amino
      acid composition of the musculature, putatively reflecting increases in
      connective tissue and decreases in protein synthesis that are associated with
      beta-GPA treatment. These results suggest that beta-GPA modestly affects fish
      muscle in a manner similar to that observed in mammals, and that beta-GPA may
      have application to aquaculture by providing a more practical means of generating
      some of the beneficial effects of exercise in fishes.

PMID- 29175486
TI  - Targeting the 15-keto-PGE2-PTGR2 axis modulates systemic inflammation and
      survival in experimental sepsis.
AB  - Sepsis is a systemic inflammation accompanied by multi-organ dysfunction due to
      microbial infection. Prostaglandins and their metabolites have long been studied
      for their importance in regulating the innate immune response. 15-keto-PGE2 (15k
      PGE2) is a prostaglandin E2 (PGE2) metabolite, whose further processing is
      catalyzed by prostaglandin reductase 2 (PTGR2). We showed disruption of the Ptgr2
      gene in mice improves the survival rate under both LPS- and cecum
      ligation/puncture (CLP)-induced experimental sepsis. Knockdown of PTGR2 showed
      significant accumulation of intracellular 15k-PGE2 in activated macrophages. Both
      PTGR2 knockdown and exogenous treatment with 15k-PGE2 resulted in reduced pro
      inflammatory cytokines production in LPS-stimulated RAW264.7 cells or bone marrow
      derived macrophages (BMDM). The same treatment in RAW264.7 and BMDM also led to
      increased levels of the anti-oxidative transcription factor, Nuclear factor
      (erythroid-2) related factor-2 (NRF2), augmented anti-oxidant response element
      (ARE)-mediated reporter activity and upregulated expression of the corresponding
      anti-oxidant genes. 15k-PGE2 further demonstrated modification to Kelch-like ECH
      associated protein 1 (Keap1), a negative regulator of Nrf2, at cysteine 288
      (Cys288) site post-translationally. Finally, 15k-PGE2-treated mice were found to
      be more resistant to experimental sepsis. Taken together, our study affirms the
      significance of PTGR2 and 15k-PGE2 in mitigating inflammatory responses and
      suggests a novel anti-oxidative and anti-inflammatory therapy for sepsis through
      targeting PTGR2 and administering15k-PGE2.

PMID- 29175487
TI  - Transconduit puncture without per-procedural echocardiography in nonfenestrated
      extracardiac Fontan using a simplified approach guided by electroanatomic
      mapping.

PMID- 29175488
TI  - Influence of the epileptiform discharge microenvironment on the differentiation
      of oligodendrocyte precursor cells.
AB  - The use of related cell cultured models to investigate the genesis and
      development of epilepsy is beneficial for exploring the mechanism of
      epileptogenesis. Recent reports have described the myelination damage caused by
      epilepsy in animal models; however, limited reports have focused on the influence
      of epilepsy on remyelination in vitro. The current study was designed to
      investigate the effect of the epileptiform discharge microenvironment on the
      differentiation of oligodendrocyte precursor cells (OPCs). Neurons with
      epileptiform discharge released more glutamic acid than normal neurons, which was
      detected by HPLC. The RT-qPCR, immunofluorescence and Western Blot results showed
      myelin basic protein (MBP) loss in the epileptiform discharge neuron
      microenvironment, with increased GluR2 subunit expression. In addition, an alpha
      amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor antagonist
      altered the influence of epilepsy on OPC differentiation. This study confirmed
      the positive effect of epilepsy on the differentiation of OPCs and verified the
      critical role of glutamic acid and the AMPA receptor in this process, which
      provides a potential treatment strategy for epilepsy.

PMID- 29175489
TI  - Diffusion tensor imaging identifies presymptomatic axonal degeneration in the
      spinal cord of ALS mice.
AB  - Extensive pathological evidence indicates that axonal degeneration represents an
      early and critical event in amyotrophic lateral sclerosis (ALS). Unfortunately,
      few MRI studies have focused in the early detection of white matter (WM)
      alterations in the spinal cord region. To unveil these WM changes, we performed
      high resolution diffusion tensor imaging (DTI) and correlated the results with
      histological analysis of adjacent slices taken from the spinal cords of
      presymptomatic mice. The DTI studies demonstrated a significant reduction in
      fractional anisotropy (FA) as well as axial diffusivities (AD) and an increase in
      radial diffusivity (RD), predominantly at lower segments of the spinal cord.
      Increases in FA and a reduction in AD and RD were observed in spinal cord (SC)
      gray matter (GM). Diffusion changes are associated with early and progressive
      alterations in axonal connectivity following a distal to proximal progression.
      Histological data tagging neuronal, axonal and glial cell markers demonstrated
      presymptomatic alterations in spinal cord WM and GM. This study demonstrates that
      DTI methods are optimal preclinical imaging tools to detect structural anomalies
      in WM and GM spinal cord during early stages of the disease.

PMID- 29175490
TI  - Impact of two follow-up schemes on morbidity management and disability prevention
      (MMDP) programme for filarial lymphedema in Matara, Sri Lanka.
AB  - Alleviating morbidity due to lymphatic filariasis (LF)-especially in elderly
      patients who are rather ignorant-is presently the biggest challenge for the
      national filariasis campaign. We introduced two follow-up schemes and compared
      each other to address three key programmatic issues (1) locating patients, (2)
      educating patients, family members on practice of lymphoedema self-care (3) well
      sustained daily self-care. Hundred and seven lymphoedema patients were introduced
      to the new Community Home Based Care (CHBC) programme as a part of MMDP programme
      at their homes. Twenty seven of 107 patients were selected by purposive sampling
      and followed-up under two schemes, 14 in Daily follow-up (DFU) scheme and 13 in
      Monthly follow-up (MFU) scheme. Impact was assessed using a KAP score, number of
      entry lesions (EL) and number of ADL episodes, limb volume, its appearance,
      changes in the quality of life and gained benefits. Visiting patients in their
      homes to introduce lymphoedema care programme was a success. KAP scores of the
      more important activities on lymphoedema care were significantly higher in DFU
      scheme. Number of patients (51.9%; 14/27) who had EL/s at baseline reduced
      significantly to 18.5% (5/27) at one year follow-up. The mean numbers of ADL
      episodes/year reduced significantly in both schemes. Six photographs of 27 showed
      obvious improvement in lymphoedema and its grade. Mean volume of lymphoedema
      reduced significantly in both schemes at one year no significant difference
      between schemes. Benefit score at one year revealed that the patients in DFU
      scheme received significantly higher amount of benefits compared to MFU scheme.
      In conclusion daily instruction has significantly motivated the patient and
      his/her family bringing a new hope.

PMID- 29175491
TI  - Deformation mechanism and mechanical properties of a thermomechanically processed
      beta Ti-28Nb-35.4Zr alloy.
AB  - The effects of thermomechanical treatment on the microstructure and mechanical
      properties of a newly developed beta titanium alloy, i.e., Ti-28Nb-35.4Zr (wt%,
      hereafter denoted Ti-Nb-Zr) were investigated. The as-cast Ti-Nb-Zr alloy was
      subjected to solution treatment at 890 degrees C for 1h, after which its
      thickness was reduced by 20%, 56%, 76%, and 86% via cold rolling. Results
      indicated that annealing at 890 degrees C for 1h after cold rolling at a
      thickness reduction ratio of 86% resulted in a phase transformation from the
      stress-induced alpha" and omega into beta, leading to a recrystallization of a
      uniform single beta phase. The recrystallized Ti-Nb-Zr alloy exhibited a tensile
      strength of 633MPa, Young's modulus of 63GPa, and elongation at rupture of 13%,
      respectively. The cold rolled specimens showed a higher Young's modulus than that
      of the recrystallized specimen due to the stress-induced omega phase.
      Transmission electron microscopy (TEM) analysis revealed that omega, alpha" and
      beta phases co-existed in the microstructure of the cold-rolled specimens.
      Electron backscatter diffraction analysis revealed that the deformation
      mechanisms during thermomechanical processing included kink bands, {332}<113>
      twins and shear bands; and the predominant deformation mechanism depended on the
      extent of CR deformation.

PMID- 29175492
TI  - Shrinkage / stress reduction and mechanical properties improvement in restorative
      composites formulated with thio-urethane oligomers.
AB  - Thio-urethane oligomers (TUs) have been shown to favorably modify methacrylate
      networks to reduce stress and significantly increase fracture toughness. Since
      those are very desirable features in dental applications, the objective of this
      work was to characterize restorative composites formulated with the addition of
      TUs. TUs were synthesized by combining thiols - pentaerythritol tetra-3
      mercaptopropionate (PETMP) or trimethylol-tris-3-mercaptopropionate (TMP) - with
      isocyanates - 1,6-Hexanediol-diissocyante (HDDI) (aliphatic) or 1,3-bis(1
      isocyanato-1-methylethyl)benzene (BDI) (aromatic) or dicyclohexylmethane 4,4'
      Diisocyanate (HMDI) (cyclic), at 1:2 isocyanate:thiol, leaving pendant thiols.
      20wt% TU were added to BisGMA-TEGDMA (70-30%). To this organic matrix, 70wt%
      silanated inorganic fillers were added. Near-IR was used to follow methacrylate
      conversion and rate of polymerization (Rpmax). Mechanical properties were
      evaluated in three-point bending (ISO 4049) for flexural strength/modulus (FS/FM)
      and toughness (T), and notched specimens (ASTM Standard E399-90) for fracture
      toughness (KIC). Polymerization stress (PS) was measured on the Bioman.
      Volumetric shrinkage (VS) was measured with the bonded disk technique. Glass
      transition temperature (Tg) and heterogeneity of network were obtained with
      dynamic mechanical analysis. The addition of TUs led to an increase in mechanical
      properties (except for Tg and FS). Fracture toughness ranged from 1.6-1.94MPam1/2
      for TU-modified groups, an increase of 33-61% in relation to the control (1.21 +/
      0.1MPam1/2). Toughness showed a two-fold increase in relation to the control:
      from 0.91MPa to values ranging from 1.70-1.95MPa. Flexural modulus was
      statistically higher for the TU-modified groups. The Tg, as expected, decreased
      for all TU groups due to the greater flexibility imparted to the network (which
      also explains the increase in toughness and fracture toughness). Narrower tan
      delta peaks suggest more homogeneous networks for the TU-modified materials,
      though differences were marked only for TMP_AL. Degree of conversion was not
      affected by the addition of TUs. VS was similar for all groups, with one
      exception where VS dropped (PETMP-cyclic). Finally, PS showed a reduction of 23
      57% for TU-modified groups (6.7 +/- 1.3 to 11.9 +/- 1.0MPa) in relation to the
      control (15.56 +/- 1.4MPa). The addition of thio-urethane oligomers was able to
      reduce polymerization stress by up to 57% while increasing fracture toughness by
      up to 61%.

PMID- 29175493
TI  - Efficiency and safety of ketamine for pain relief after laparoscopic
      cholecystectomy: A meta-analysis from randomized controlled trials.
AB  - OBJECTIVE: This meta-analysis aims to evaluate the effectiveness of intravenous
      infusion of ketamine for pain control after laparoscopic cholecystectomy (LC).
      METHODS: A systematic search was performed in PubMed (1966-2017.08), Medline
      (1966-2017.08), Embase (1980-2017.08), ScienceDirect (1985-2017.08) and the
      Cochrane Library. Only randomized controlled trials (RCTs) were included. Meta
      analysis was performed using Stata 11.0 software. RESULTS: A total of six RCTs
      were retrieved involving 294 patients. The present meta-analysis showed that
      there were significant differences between groups in terms of visual analogue
      scale scores at 12 h (WMD = -0.478, 95% CI: -0.934 to -0.021, P = 0.040), 24 h
      (WMD = -0.550, 95% CI: -1.099 to -0.002, P = 0.049), and 48 h (WMD = -0.350, 95%
      CI: -0.678 to -0.021, P = 0.037) after LC. Significant differences were found
      regarding opioid consumption at 12 h (WMD = -2.820, 95% CI: -5.170 to -0.470, P =
      0.019), 24 h (WMD = -3.816, 95% CI: -7.155 to -0.478, P = 0.025), and 48 h (WMD =
      -2.210, 95% CI: -4.046 to -0.375, P = 0.018) after LC. CONCLUSION: Intravenous
      ketamine infusion significantly reduced postoperative pain scores and opioid
      consumption after LC. In addition, there were fewer adverse effects in the
      ketamine groups. Higher quality RCTs are still required for further research.

PMID- 29175494
TI  - Unfolding the hippocampus: An intrinsic coordinate system for subfield
      segmentations and quantitative mapping.
AB  - The hippocampus, like the neocortex, has a morphological structure that is
      complex and variable in its folding pattern, especially in the hippocampal head.
      The current study presents a computational method to unfold hippocampal grey
      matter, with a particular focus on the hippocampal head where complexity is
      highest due to medial curving of the structure and the variable presence of
      digitations. This unfolding was performed on segmentations from high-resolution,
      T2-weighted 7T MRI data from 12 healthy participants and one surgical patient
      with epilepsy whose resected hippocampal tissue was used for histological
      validation. We traced a critical image feature composed of the hippocampal sulcus
      and stratum radiatum lacunosum-moleculare, (SRLM) in these images, then employed
      user-guided semi-automated techniques to detect and subsequently unfold the
      surrounding hippocampal grey matter. This unfolding was performed by solving
      Laplace's equation in three dimensions of interest (long-axis, proximal-distal,
      and laminar). The resulting 'unfolded coordinate space' provides an intuitive way
      of mapping the hippocampal subfields in 2D space (long-axis and proximal-distal),
      such that similar borders can be applied in the head, body, and tail of the
      hippocampus independently of variability in folding. This unfolded coordinate
      space was employed to map intracortical myelin and thickness in relation to
      subfield borders, which revealed intracortical myelin differences that closely
      follow the subfield borders used here. Examination of a histological resected
      tissue sample from a patient with epilepsy reveals that our unfolded coordinate
      system has biological validity, and that subfield segmentations applied in this
      space are able to capture features not seen in manual tracing protocols.

PMID- 29175495
TI  - Dynamics of perceptual decisions about symmetry in visual cortex.
AB  - Neuroimaging studies have identified multiple extra-striate visual areas that are
      sensitive to symmetry in planar images (Kohler et al., 2016; Sasaki et al.,
      2005). Here, we investigated which of these areas are directly involved in
      perceptual decisions about symmetry, by recording high-density EEG in
      participants (n = 25) who made rapid judgments about whether an exemplar image
      contained rotation symmetry or not. Stimulus-locked sensor-level analysis
      revealed symmetry-specific activity that increased with increasing order of
      rotation symmetry. Response-locked analysis identified activity occurring between
      600 and 200 ms before the button-press, that was directly related to perceptual
      decision making. We then used fMRI-informed EEG source imaging to characterize
      the dynamics of symmetry-specific activity within an extended network of areas in
      visual cortex. The most consistent cortical source of the stimulus-locked
      activity was VO1, a topographically organized area in ventral visual cortex, that
      was highly sensitive to symmetry in a previous study (Kohler et al., 2016).
      Importantly, VO1 activity also contained a strong decision-related component,
      suggesting that this area plays a crucial role in perceptual decisions about
      symmetry. Other candidate areas, such as lateral occipital cortex, had weak
      stimulus-locked symmetry responses and no evidence of correlation with response
      timing.

PMID- 29175496
TI  - Motion processing after sight restoration: No competition between visual recovery
      and auditory compensation.
AB  - The present study tested whether or not functional adaptations following
      congenital blindness are maintained in humans after sight-restoration and whether
      they interfere with visual recovery. In permanently congenital blind individuals
      both intramodal plasticity (e.g. changes in auditory cortex) as well as
      crossmodal plasticity (e.g. an activation of visual cortex by auditory stimuli)
      have been observed. Both phenomena were hypothesized to contribute to improved
      auditory functions. For example, it has been shown that early permanently blind
      individuals outperform sighted controls in auditory motion processing and that
      auditory motion stimuli elicit activity in typical visual motion areas. Yet it is
      unknown what happens to these behavioral adaptations and cortical reorganizations
      when sight is restored, that is, whether compensatory auditory changes are lost
      and to which degree visual motion processing is reinstalled. Here we employed a
      combined behavioral-electrophysiological approach in a group of sight-recovery
      individuals with a history of a transient phase of congenital blindness lasting
      for several months to several years. They, as well as two control groups, one
      with visual impairments, one normally sighted, were tested in a visual and an
      auditory motion discrimination experiment. Task difficulty was manipulated by
      varying the visual motion coherence and the signal to noise ratio, respectively.
      The congenital cataract-reversal individuals showed lower performance in the
      visual global motion task than both control groups. At the same time, they
      outperformed both control groups in auditory motion processing suggesting that at
      least some compensatory behavioral adaptation as a consequence of a complete
      blindness from birth was maintained. Alpha oscillatory activity during the visual
      task was significantly lower in congenital cataract reversal individuals and they
      did not show ERPs modulated by visual motion coherence as observed in both
      control groups. In contrast, beta oscillatory activity in the auditory task,
      which varied as a function of SNR in all groups, was overall enhanced in
      congenital cataract reversal individuals. These results suggest that intramodal
      plasticity elicited by a transient phase of blindness was maintained and might
      mediate the prevailing auditory processing advantages in congenital cataract
      reversal individuals. By contrast, auditory and visual motion processing do not
      seem to compete for the same neural resources. We speculate that incomplete
      visual recovery is due to impaired neural network turning which seems to depend
      on early visual input. The present results demonstrate a privilege of the first
      arriving input for shaping neural circuits mediating both auditory and visual
      functions.

PMID- 29175497
TI  - Spatiotemporal characterization of breathing-induced B0 field fluctuations in the
      cervical spinal cord at 7T.
AB  - Magnetic resonance imaging and spectroscopy of the spinal cord stand to benefit
      greatly from the increased signal-to-noise ratio of ultra-high field. However,
      ultra-high field also poses considerable technical challenges, especially related
      to static and dynamic B0 fields. Breathing causes the field to fluctuate with the
      respiratory cycle, giving rise to artifacts such as ghosting and apparent motion
      in images. We here investigated the spatial and temporal characteristics of
      breathing-induced B0 fields in the cervical spinal cord at 7T. We analyzed the
      magnitude and spatial profile of breathing-induced fields during breath-holds in
      an expired and inspired breathing state. We also measured the temporal field
      evolution during free breathing by acquiring a time series of fast phase images,
      and a principal component analysis was performed on the measured field evolution.
      In all subjects, the field shift was largest around the vertebral level of C7 and
      lowest at the top of the spinal cord. At C7, we measured peak-to-peak field
      fluctuations of 36 Hz on average during normal free breathing; increasing to on
      average 113 Hz during deep breathing. The first principal component could explain
      more than 90% of the field variations along the foot-head axis inside the spinal
      cord in all subjects. We further implemented a proof-of-principle shim
      correction, demonstrating the feasibility of using the shim system to compensate
      for the breathing-induced fields inside the spinal cord. Effective correction
      strategies will be crucial to unlock the full potential of ultra-high field for
      spinal cord imaging.

PMID- 29175498
TI  - Neuroimaging of stroke recovery from aphasia - Insights into plasticity of the
      human language network.
AB  - The role of left and right hemisphere brain regions in language recovery after
      stroke-induced aphasia remains controversial. Here, we summarize how neuroimaging
      studies increase the current understanding of functional interactions,
      reorganization and plasticity in the language network. We first discuss the
      temporal dynamics across the time course of language recovery, with a main focus
      on longitudinal studies from the acute to the chronic phase after stroke. These
      studies show that the functional contribution of perilesional and spared left
      hemisphere as well as contralesional right hemisphere regions to language
      recovery changes over time. The second section introduces critical variables and
      recent advances on early prediction of subsequent outcome. In the third section,
      we outline how multi-method approaches that combine neuroimaging techniques with
      non-invasive brain stimulation elucidate mechanisms of plasticity and
      reorganization in the language network. These approaches provide novel insights
      into general mechanisms of plasticity in the language network and might
      ultimately support recovery processes during speech and language therapy.
      Finally, the neurobiological correlates of therapy-induced plasticity are
      discussed. We argue that future studies should integrate individualized
      approaches that might vary the combination of language therapy with specific non
      invasive brain stimulation protocols across the time course of recovery. The way
      forward will include the combination of such approaches with large data sets
      obtained from multicentre studies.

PMID- 29175499
TI  - Visualization of porcine eye anatomy by X-ray microtomography.
AB  - The aim of our study is to obtain, as accurately as possible, porcine ocular
      tissue visualization using microtomography (micro-CT) method. We propose image
      contrast enhancement by different staining procedures with combination of micro
      CT scanning. Porcine eye globes were investigated with Bruker-SkyScan 1172 micro
      CT. We used 4F1G and Bouin's as sample fixation solutions and tincture of iodine,
      100% Lugol, phosphotungstic acid and 1% osmium tetroxide solutions for staining.
      Quantitative and qualitative analysis was performed based on micro-CT
      reconstruction images histograms and 3D volume rendering models of investigated
      samples. This investigation showed that staining methods improved micro-CT image
      quality in case of ocular anatomy visualization. Characteristic profiles of the
      grey level distributions and quality of the cross-section and 3D volume rendering
      images confirmed the staining effect. Most significant contrast enhancement was
      obtained after 96 h staining in osmium tetroxide and Lugol solutions. The images
      of eye anatomical structures were characterized: cornea, lens, iris, ciliary
      body, vitreous, retina, choroid and sclera, vasculature and optic nerve. Staining
      of porcine eye globes used in this work leads to quality improvement of the micro
      CT imaging. The most contrast images were obtained for Lugol and osmium tetroxide
      solutions. Different affinity of staining solutions to eye anatomical structures
      has been observed in the obtained images. Osmium tetroxide provides sharper image
      of conjunctiva, sclera, choroid, retina, iris and ciliary body structure. Lugol
      staining leads to more accurate vessels, cornea and optic nerve imagining.

PMID- 29175500
TI  - Stress hormones and verbal memory in young people over the first 12 weeks of
      treatment for psychosis.
AB  - AIMS: Memory impairment in psychosis may be mediated through detrimental effects
      of hypothalamic-pituitary-adrenal (HPA) axis function. This study prospectively
      investigated the relationship between cortisol, sulphate dehydroepiandrosterone
      (DHEA(S) and cortisol: DHEA(S) ratio and memory in 35 first-episode psychosis
      (FEP) patients during the first 12 weeks of treatment and 23 healthy controls
      (HC). METHODS: Morning blood sampling and tests of attention, working memory and
      verbal memory occurred at baseline and 12-week follow-up. RESULTS: FEP and HC
      groups did not significantly differ in levels of cortisol, DHEA(S) or their ratio
      at baseline or over 12-weeks. The FEP group performed significantly below HC on
      all cognitive measures at baseline and over 12-weeks. Cortisol levels were
      unrelated to cognition in both groups. At baseline, DHEA(S) was positively
      associated with attention in HCs, but negatively associated with attention in FEP
      participants. Change in DHEA(S) was negatively associated with change in memory
      over 12-weeks in both groups. At 12-weeks, there was a negative correlation
      between the cortisol: DHEA(S) ratio and attention in both groups. CONCLUSIONS:
      These findings are mostly in contrast to findings in chronic schizophrenia.
      Investigation at different illness phases and over longer-follow-up periods is
      required to determine the complex relationship between HPA-axis and memory
      functioning in psychosis.

PMID- 29175501
TI  - Choice of a suicide method: Trends and characteristics.
AB  - The aim of this study was to examine (1) suicide trends by most prevalent methods
      in Queensland, Australia, during 2000-2015, and (2) characteristics of people by
      choice of suicide method in 2000-2013. Data were obtained from the Queensland
      Suicide Register, which includes police and toxicology reports, post-mortem
      autopsy and Coroner's findings. Poisson and Joinpoint regression were used to
      study the first aim, and uni-variate and multi-variate logistic regression
      analyses were applied to investigate the second aim. Suicide method trends showed
      a significant increase in hanging for both sexes and poisoning with drugs for
      females, while there was a decline for poisoning by other means for both sexes,
      and 'other methods' decreased for males. Changes in the trends have altered the
      order of suicide methods, especially in males. Analyses of 8140 suicides were
      composed by the choice of method, distinguishable profiles by their demographic,
      clinical and social characteristics, such as having mental or physical illness or
      different recent life stressors were identified. This suggests that socio
      cultural acceptability, and availability are the key drivers in the choice of
      suicide methods. Continuing increases in hanging is a big challenge in suicide
      prevention due to its lethality, easy realisation and its increasing
      acceptability.

PMID- 29175502
TI  - The diffusion of the diagnostic term bipolar disorder among the German public.
AB  - In 2005, 15 years after the introduction of the diagnosis in DSM-III, a telephone
      survey in Germany revealed that the public was still unfamiliar with the term
      bipolar disorder. Only 5.3% of those questioned knew at the time that it denotes
      a mental illness. In the meantime, efforts have been made to spread the concept
      among the public. In the media there has been increasing mention of the disorder.
      Another telephone survey in 2017 showed that familiarity with the diagnostic term
      has grown substantially. 54.0% of respondents now connected the term bipolar
      disorder with a mental illness.

PMID- 29175503
TI  - Non literal language comprehension in a large sample of first episode psychosis
      patients in adulthood.
AB  - To date no data still exist on the comprehension of figurative language in the
      early phases of psychosis. The aim of this study is to investigate for the first
      time the comprehension of metaphors and idioms at the onset of the illness. Two
      hundred-twenty eight (228) first episode psychosis (FEP) patients (168 NAP, non
      affective psychosis; 60 AP, affective psychosis) and 70 healthy controls (HC)
      were assessed. Groups were contrasted on: a) type of stimulus (metaphors vs
      idioms) and b) type of response (OPEN = spontaneous explanations vs CLOSED =
      multiple choice answer). Moreover, a machine learning (ML) approach was adopted
      to classifying participants. Both NAP and AP had a poorer performance on OPEN
      metaphors and idioms compared to HC, with worse results on spontaneous
      interpretation of idioms than metaphors. No differences were observed between NAP
      and AP in CLOSED tasks. The ML approach points at CLOSED idioms as the best
      discriminating variable, more relevant than the set of pre-frontal and IQ scores.
      Deficits in non-figurative language may represent a core feature of psychosis.
      The possibility to identify linguistic features discriminating FEP may support
      the early recognition of patients at risk to develop psychosis, guiding provision
      of personalized and timely interventions.

PMID- 29175504
TI  - Neurological soft signs, dissociation and alexithymia in patients with obsessive
      compulsive disorder (OCD) and healthy subjects.
AB  - A body of evidence has supported that patients with obsessive-compulsive disorder
      (OCD) have increased rates of various neurological soft signs (NSS) compared to
      controls. Various lines of research has documented robust relationships between
      OCD and dissociative symptomatology. The study aimed to examine the associations
      between obsessive-compulsive symptoms, dissociative experiences alexithymia, and
      NSS. The study included thirty OCD patients and thirty healthy controls, matched
      for age, marital status, education, and income. The Neurological Evaluation Scale
      (NES), Padua Inventory-Revised (PI-R), Dissociative Experiences Scale (DES) and
      Toronto Alexithymia Scale (TAS-20) were administered. In comparison to healthy
      controls, patients with OCD had difficulty sequencing for complex motor acts and
      greater absorption/ imaginative involvement. Using latent class analysis, the
      study sample was classified into two homogenous subsets as mild NSS (n = 45) and
      severe NSS (n = 15). Majority of the participants who were grouped into severe
      NSS latent class were OCD patient (n = 14, 93.3%). Furthermore, those with severe
      NSS reported greater levels of alexithymia and more severe obsessive-compulsive
      symptoms, particularly precision. We concluded that relationships between OCD
      severity and NSS appear to be of crucial importance. Our data along with
      accumulated evidence suggest that OCD associated with pronounced NSS may
      represent a specific subtype of the disorder.

PMID- 29175505
TI  - Characteristics of induced pluripotent stem cells from clinically divergent
      female monozygotic twins with Danon disease.
AB  - RATIONALE: Induced pluripotent stem cells (iPSCs) have been generated from
      patients with various forms of disease, including Danon disease (DD); however,
      few reports exist regarding disease-specific iPSCs derived from clinically
      divergent monozygotic twins. OBJECTIVE: We examined the characteristics of iPSCs
      and iPSC-derived cardiomyocytes (iPSC-CMs) generated from clinically divergent
      monozygotic female twins with DD. METHODS AND RESULTS: We generated iPSCs derived
      from T-cells isolated from clinically divergent, 18-year-old female twins with DD
      harboring a mutation in LAMP2 at the intron 6 splice site (IVS6+1_4delGTGA). Two
      divergent populations of iPSCs could prepare from each twin despite of their
      clinical divergence: one with wild-type LAMP2 expression (WT-iPSCs) and a second
      with mutant LAMP2 expression (MT-iPSCs). The iPSCs were differentiated into iPSC
      CMs and then autophagy failure was observed only in MT-iPSC-CMs by electron
      microscopy, tandem fluorescent-tagged LC3 analysis, and LC3-II western blotting.
      Under these conditions, X-chromosome inactivation (XCI) was determined by PCR for
      the (CAG)n repeat in the androgen receptor gene, revealing an extremely skewed
      XCI pattern with the inactivated paternal wild-type and maternal mutant X
      chromosomes in MT-iPSCs and WT-iPSCs, respectively, from each twin. CONCLUSION:
      Regardless of their clinical differences, we successfully established two sets of
      iPSC lines that expressed either wild-type or mutant LAMP2 allele from each
      monozygotic twin with DD, of which only the populations expressing mutant LAMP2
      showed autophagic failure.

PMID- 29175506
TI  - CD26 expression is down-regulated on CD8+ T cells in patients with Hashimoto's
      thyroiditis.
AB  - The immune mechanism underlying Hashimoto's thyroiditis (HT) remains unclear.
      CD26, also known as dipeptidyl peptidase 4 (DPP-4), is a multifunctional molecule
      involved in the pathophysiology of autoimmune diseases. This study aimed to
      investigate the role of CD26 in the pathogenesis of HT. Peripheral blood was
      drawn from 20 healthy controls and 31 HT patients (19 mild HT patients and 12
      severe HT patients). Plasma sCD26 concentrations were measured by ELISA, and
      sCD26 enzymatic activity was assessed using a luciferase-based assay. The
      expression levels of membrane-bound CD26 were analyzed by flow cytometry. Plasma
      sCD26 concentrations were lower in HT patients than in healthy controls, although
      the difference in sCD26 concentrations between the two groups did not reach
      statistical significance (P=0.07). The percentages of CD8+ T cells and Tc1 cells
      with CD26 expression were decreased in HT patients compared with those in healthy
      controls, and the mean fluorescence intensity (MFI) values of CD26 on CD8+ T
      cells and Tc17 cells in HT patients were significantly lower than in healthy
      controls (P<0.05). In HT patients, the expression of CD26 on CD8+ T cells and Tc
      subsets was decreased in the hypothyroidism group compared with that in the
      euthyroid group (P<0.05). These results suggest that the sCD26 concentrations and
      membrane-bound CD26 levels on CD8+ T cells are aberrant in HT and that the
      reduced CD26 expression may be involved in the progression of HT.

PMID- 29175507
TI  - The mast cell stabilizing activity of Chaga mushroom critical for its therapeutic
      effect on food allergy is derived from inotodiol.
AB  - While an anti-allergic effect of Chaga mushroom (Inonotus obliquus) has been
      indicated, its therapeutic effect on allergy and immunoregulatory mechanisms and
      chemical constituents directly responsible for that are hardly known. We examined
      the effect of 70% ethanol extract of Chaga mushroom (EE) and its dichloromethane
      (DF) and aqueous (AF) fractions using a mouse model of chicken ovalbumin (cOVA)
      induced food allergy, and found that only EE and DF ameliorated allergy symptoms
      to a significant extent. The in vivo mast cell-stabilizing activity was also
      found only in EE and DF whereas the activities to suppress Th2 and Th17 immune
      responses and cOVA-specific IgE production in the small intestine were observed
      in all three treatment regimens, implying that inhibition of the mast cell
      function by lipophilic compounds was vital for the therapeutic effect. Results
      also indicated that inotodiol, a triterpenoid predominantly present in DF, played
      an active role as a mast cell stabilizer.

PMID- 29175508
TI  - TNFalpha induces tolerant production of CXC chemokines in colorectal cancer
      HCT116 cells via A20 inhibition of ERK signaling.
AB  - Ubiquitin editing enzyme A20 functions as a tumor suppressor in various cancer.
      However, the mechanism for A20 regulation of cancer progress is not fully
      understood. In this study, we found that in human colorectal cancer HCT116 cells,
      TNFalpha induced a tolerant production of CXC chemokines, including CXCL1, 2, and
      8 in a dose and time dependent manner. TNFalpha pre-treatment of HCT116 cells
      down-regulated the chemokine production induced by TNFalpha re-treatment.
      TNFalpha induced the phosphorylation of MAPKs ERK, JNK, P38 and NF-kappaB P65,
      but only ERK inhibition decreased TNFalpha-induced chemokine production. Both RT
      PCR and FACS results showed that TNFalpha treatment did not regulate the
      expression of TNF receptors. However, TNFalpha up-regulated the expression of A20
      at both mRNA and protein levels significantly. TNFalpha pre-treatment inhibited
      the signal transduction of MAPKs induced by TNFalpha re-stimulation, and A20 over
      expression decreased the signal transduction of ERK and P38. Meanwhile, A20
      inhibition by RNA interference reversed chemokine down-regulation induced by
      TNFalpha re-stimulation after TNFalpha pre-treatment. Taken together, these
      results suggested that in human colorectal cancer cells, A20 may function to
      inhibit cancer progression via down-regulation of TNFalpha-induced chemokine
      production by suppression of ERK signaling.

PMID- 29175510
TI  - CT scan assessment in salivary gland lithiasis diagnosis.
AB  - INTRODUCTION: The aim of the study was to assess computed tomography (CT) scan
      efficiency for the diagnosis of salivary lithiasis. METHODS: Patients who were
      included were all the patients who consulted in our department for main salivary
      gland (submandibular and parotid) obstruction symptoms between June 2014 and
      December 2016. A CT scan without injection was prescribed for all of them. The
      163 patients were divided into two groups after the CT scan: patients with and
      without lithiasis. During surgery, we confirmed the presence or absence of the
      lithiasis previously diagnosed on the CT scan. The patients were divided in two
      groups: case and control groups. For statistical analysis, the sensitivity,
      specificity, and the negative and positive predictive values of the preoperative
      CT scan were calculated. RESULTS: A total of 163 patients with a salivary
      obstructive syndrome were included. On the CT scans, we found lithiases
      (hyperdense images) in 157 glands ("CT scan?" group), and we found no lithiasis
      in 6 glands ("CT scan" group). In the "CT scan?" group, 203 lithiases were
      present. During surgery, we found and removed lithiases in 155 patients (case
      group), and 8 patients had no lithiases (control group). The overall sensitivity,
      specificity, positive predictive value, and negative predictive values of the CT
      scan for the detection of lithiasis were 100%, 75%, 99%, and 100%, respectively.
      The specificity of CT scans for the lithiasis located in the anterior and middle
      third of the duct was 100%. DISCUSSION: According to our study, the CT scan is
      very efficient in diagnosing salivary main gland lithiases in patients with an
      obstructive syndrome.

PMID- 29175511
TI  - Speech evaluation after intravelar veloplasty. How to use Borel-Maisonny
      classification in the international literature?
AB  - OBJECTIVE: Comparing functional outcomes after velar repair appeared to be
      difficult because of the absence of international standardized scale. Moreover
      most of the studies evaluating speech after cleft surgery present multiple
      biases. The aim of our study was to assess speech outcomes in a homogeneous group
      of patients, and to define an equivalence table between different speech scales.
      MATERIALS AND METHODS: Patients with isolated cleft lip and palate (CLP),
      operated in our unit by the same senior surgeon were included. All patient were
      operated according to the same protocol (cheilo-rhinoplasty and intravelar
      veloplasty at 6 months, followed by a direct closure of the hard palate at 15
      months). Speech evaluation was performed after 3 year-old and before the alveolar
      cleft repair. Borel-Maisonny scale and nasometry were used for speech evaluation.
      RESULTS: Twenty-four patients were included: 17 unilateral CLP and 7 bilateral
      CLP. According to the Borel-Maisonny classifications, 82.5% were ranged phonation
      1, 1-2 or 2b. Nasometry were normal in almost 60% of cases. CONCLUSIONS: This
      study showed the efficiency of our protocol, and intravelar veloplasty. Moreover
      we proposed an equivalence table for speech evaluation scale.

PMID- 29175512
TI  - Altering D1 receptor activity in the basolateral amygdala impairs fear
      suppression during a safety cue.
AB  - Accurate discrimination among cues signifying reward, danger or safety initiates
      the proper emotional response in order to guide behavior. Appropriate conditioned
      inhibition of fear in the presence of a safety cue would allow an organism to
      engage in reward seeking behaviors. There is currently little known about the
      mechanisms of reward, fear and safety cue discrimination and how a safety cue can
      inhibit fear and release reward seeking from inhibition. Here we assess reward,
      fear and safety cue learning together using a behavioral paradigm that has
      identified neurons that discriminate among these cues in the basolateral amygdala
      (BLA) (Sangha, Chadick, & Janak, 2013). Dopamine signaling in the BLA has been
      implicated in discriminatory reward learning, learned fear responses and fear
      extinction. We tested the hypothesis that D1 receptor activity will influence
      reward-fear-safety cue discrimination by using the D1 receptor agonist, SKF-3839,
      and antagonist, SCH-23390, either systemically or within the BLA during
      discrimination learning in male Long Evans rats. We show that both the agonist
      and antagonist interfered with fear suppression in the presence of the safety
      cue, when administered systemically or when infused directly into the BLA. This
      indicates that altering D1 receptor activity in the basolateral amygdala impairs
      fear suppression during a safety cue. Neither the agonist or antagonist had a
      consistent negative impact on discriminatory reward seeking when infused into the
      BLA. However, systemic administration of the D1 receptor agonist did reduce
      reward seeking behavior during a task that included fear and safety cues. We did
      not observe a negative impact on reward seeking during systemic administration of
      a D1 receptor agonist in a task that only included reward cue + sucrose and
      nonreward cue + no sucrose pairings. This indicates the impairments we saw with
      the systemically applied agonist in the safety-fear-reward cue discrimination
      task were more likely due to effects on fear and/or motivation rather than on cue
      discrimination. Together, our data indicate that altered dopamine D1 receptor
      activity in the BLA may be a potential mechanism that leads to the impairment in
      fear suppression to the safety signal seen with PTSD patients.

PMID- 29175513
TI  - Sleep augments training-induced improvement in working memory in children and
      adults.
AB  - Sleep plays an important role in forming procedural motor memories. Whether sleep
      plays a similar role for cognitive procedures related to working memory function,
      is not yet clear. Here we investigated if sleep enhances training-induced
      improvements in working memory in children. Because children show more intense
      slow wave sleep (e.g., higher slow wave activity, more spindles) we expected
      sleep-related improvements to be greater than in adults. Twenty-four children (10
      12 years) and 24 adults were trained on three sessions of an n-back task
      comprising three runs of blocks (6 blocks with 20 responses each) presented in
      ascending levels of difficulty. The sessions were separated by ~12 h. Between the
      training sessions, participants first spent a full night sleeping and then a
      normal day awake (evening groups) or vice versa (morning groups). We analyzed
      performance on the whole blocks and, to estimate the individual's optimum
      performance, on only the first 10 trials of each block. Results showed a distinct
      gain in training-induced working memory performance with post-training overnight
      sleep compared to wakefulness. The sleep-induced gain was revealed only for
      performance on the first block-halves and, in absolute terms, was closely
      comparable in children and adults. Taking differences in working memory
      performance into account sleep-dependent gains expressed as percentages of
      baseline performance were, however, greater in children than in adults. The data
      thus indicate that sleep after training facilitates cognitive procedures related
      to executive control, i.e., the ability to operate sequences of events in working
      memory, with a particular benefit in developing populations.

PMID- 29175514
TI  - Reward anticipation modulates the effect of stress-related increases in cortisol
      on episodic memory.
AB  - When acute stress is experienced shortly after an event is encoded into memory,
      this can slow the forgetting of the study event, which is thought to reflect the
      effect of cortisol on consolidation. In addition, when events are encoded under
      conditions of high reward they tend to be remembered better than those encoded
      under non-rewarding conditions, and these effects are thought to reflect the
      operation of the dopaminergic reward system. Although both modulatory systems are
      believed to impact the medial temporal lobe regions critical for episodic memory,
      the manner, and even the extent, to which these two systems interact is currently
      unknown. To address this question in the current study, participants encoded
      words under reward or non-reward conditions, then one half of the participants
      were stressed using the social evaluation cold pressor task and the other half
      completed a non-stress control task. After a two-hour delay, all participants
      received a free recall and recognition memory test. There were no significant
      effects of stress or reward on overall memory performance. However, for the non
      reward items, increases in stress-related cortisol in stressed participants were
      related to increases in recall and increases in recollection-based recognition
      responses. In contrast, for the reward items, increases in stress-related
      cortisol were not related to increases in memory performance. The results
      indicate that the stress and the reward systems interact in the way they impact
      episodic memory. The results are consistent with tag and capture models in the
      sense that cortisol reactivity can only affect non-reward items because
      plasticity-related products are already provided by reward anticipation.

PMID- 29175516
TI  - A lucky mistake: the splenic glands of Marcello Malpighi.
AB  - Marcello Malpighi (1628-1694) is one of the most important anatomists and
      physicians in the history of medicine. His contributions to the understanding of
      human anatomy and physiology span from the first description of capillary
      circulation to a thorough analysis of the structure and function of body glands.
      Malpighi believed that most organs consisted of glandular structures, whose
      distribution and microscopic features determine each organ-specific function. He
      also applied this view to the study of spleen anatomy, which he recognized as
      composed of 2 distinct anatomic compartments (ie, the red and the white pulp).
      Malpighi's observations on the structure and function of the spleen were first
      published in 1666 in De Viscerum Structura. In this paper, we pay tribute to this
      work, presenting Malpighi's theory of the spleen as a glandular organ. The
      rationale of Malpighi's view and its value for contemporary pathologists and
      medical researchers will also be elucidated.

PMID- 29175515
TI  - Innate immune control of alphavirus infection.
AB  - Alphaviruses are important human pathogens that cause diseases ranging from acute
      and chronic polyarthralgia to encephalitis. Transmitted by mosquito vectors,
      alphaviruses have high potential for emergence and have initiated several recent
      epidemics. The innate immune response is critical for controlling the acute phase
      of alphavirus disease, and the induction of type I interferon (IFN) is essential
      in this response. In this review, we discuss our current understanding of innate
      host sensors that initiate antiviral responses following alphavirus infection,
      and the IFN-induced effector proteins that limit alphavirus replication and
      dissemination.

PMID- 29175517
TI  - Design and simulation of a microfluidic device for acoustic cell separation.
AB  - Experimental acoustic cell separation methods have been widely used to perform
      separation for different types of blood cells. However, numerical simulation of
      acoustic cell separation has not gained enough attention and needs further
      investigation since by using numerical methods, it is possible to optimize
      different parameters involved in the design of an acoustic device and calculate
      particle trajectories in a simple and low cost manner before spending time and
      effort for fabricating these devices. In this study, we present a comprehensive
      finite element-based simulation of acoustic separation of platelets, red blood
      cells and white blood cells, using standing surface acoustic waves (SSAWs). A
      microfluidic channel with three inlets, including the middle inlet for sheath
      flow and two symmetrical tilted angle inlets for the cells were used to drive the
      cells through the channel. Two interdigital transducers were also considered in
      this device and by implementing an alternating voltage to the transducers, an
      acoustic field was created which can exert the acoustic radiation force to the
      cells. Since this force is dependent to the size of the cells, the cells are
      pushed towards the midline of the channel with different path lines. Particle
      trajectories for different cells were obtained and compared with a theoretical
      equation. Two types of separations were observed as a result of varying the
      amplitude of the acoustic field. In the first mode of separation, white blood
      cells were sorted out through the middle outlet and in the second mode of
      separation, platelets were sorted out through the side outlets. Depending on the
      clinical needs and by using the studied microfluidic device, each of these modes
      can be applied to separate the desired cells.

PMID- 29175518
TI  - Social cognitive dysfunction as a clinical marker: A systematic review of meta
      analyses across 30 clinical conditions.
AB  - Social cognition includes a range of cognitive processes that help individuals to
      understand how others think and feel. There is emerging evidence that social
      cognitive deficits may represent a transdiagnostic issue, potentially serving as
      a marker of neurological abnormality. We performed an electronic database search
      in order to identify published, peer-reviewed meta-analyses that compared facial
      emotion recognition or theory of mind task performance between individuals
      meeting clinical criteria for a psychiatric, neurological or developmental
      condition against healthy controls. We identified 31 meta-analyses eligible for
      inclusion that examined performance across relevant tasks among 30 different
      clinical populations. The results suggest that social cognitive deficits appear
      to be a core cognitive phenotype of many clinical conditions. Across the clinical
      groups, deficits in social cognitive domains were broadly similar in magnitude to
      those previously reported for more established aspects of cognition, such as
      memory and executive function. There is a need to clarify the 'real world' impact
      of these deficits, and to develop effective transdiagnostic interventions for
      those individuals that are adversely affected.

PMID- 29175509
TI  - Retinal energy demands control vascular supply of the retina in development and
      disease: The role of neuronal lipid and glucose metabolism.

PMID- 29175519
TI  - A new tridecapeptide with an octaarginine vector has analgesic therapeutic
      potential and prevents morphine-induced tolerance.
AB  - A growing body of evidence suggests that peptides may possess analgesic effects
      without tolerance development. The synthetic tetrapeptide Tyr-d-Arg-Phe-Gly-NH2
      was modified with the inclusion of a (d-Arg)8 vector to prevent the action of
      endopeptidase and to increase the duration of the analgesic action of the
      tetrapeptide when administered orally. The aim of this study was to estimate the
      analgesic efficacy of the tetrapeptide with (d-Arg)8 (tridecapeptide, TDP) in
      experimental models of acute and chronic pain. The analgesic effects of TDP were
      estimated using a model of acute visceral pain in mice (writhing test) and a
      model of chronic neuropathic pain (chronic constriction injury (CCI) of the
      sciatic nerve) in rats. The intravenous administration of morphine (0.32-1mg/kg)
      and TDP (0.32-1.8mg/kg) produced significant dose-related antinociceptive effects
      in the writhing test. The potency of TDP after i.g. administration was lower than
      that after i.v. administration but comparable with that of i.g. morphine. In the
      CCI model, TDP (0.1, 1 and 10mg/kg, i.g.) induced marked analgesia with repeated
      administration without any signs of tolerance. The single administration of TDP
      after morphine treatment (7days) produced a significant analgesic effect in
      morphine-tolerant rats, indicating the absence of cross-tolerance between these
      two drugs. The combined administration of TDP and morphine resulted in the
      reduction of analgesic tolerance to morphine. The absence of cross-tolerance to
      morphine and the ability to prevent morphine tolerance allows this compound to be
      a prospective candidate for chronic pain therapy. In order to find the target
      receptors for TDP, a docking study was performed. It was found that the molecule
      can bind to the NMDA receptor using electrostatic, hydrogen bonding and
      hydrophobic interactions.

PMID- 29175520
TI  - Alzheimer's disease-associated ubiquitin mutant Ubb+1: Properties of the carboxy
      terminal domain and its influence on biomolecular interactions.
AB  - Ubb+1, a ubiquitin (Ub) mutant protein originating from misreading of the Ub B
      gene, is found accumulated in brain tissues of Alzheimer's disease patients. The
      mutant attracts strong interest due to its possible participation in the
      molecular events leading to neurodegeneration. Ubb+1 is composed of the globular
      domain of Ub, linked to a 19-residue C-terminal peptide. Based on NMR relaxation
      and solvent accessibility measurements we obtained new insight into the molecular
      properties of Ubb+1. We further determined the thermal stability of Ubb+1 in the
      monomeric form, and in Lys48- and Lys63-linked dimers. Finally, we explored the
      influence of the C-terminal fragment on the interactions of Ubb+1 with an
      isolated UBA2 domain and with membrane mimics. Our data indicate that the C
      terminal fragment of Ubb+1 is overall highly flexible, except for a short stretch
      which appears less solvent-exposed. While influencing the hydrodynamic properties
      of the globular domain, the fragment does not establish long-lived interactions
      with the globular domain. It results that the structure and stability of Ub are
      minimally perturbed by the peptide extension. However, binding to UBA2 and to
      membrane mimics are both affected, exemplifying possible changes in biomolecular
      recognition experienced by the disease-associated Ubb+1 compared to the wild-type
      protein.

PMID- 29175521
TI  - Structural analysis of the interaction between free, glycated and fructated
      hemoglobin with propolis nanoparticles: A spectroscopic study.
AB  - Non enzymatic Glycation is the main causes of diabetic complications. Propolis is
      a natural product of different plant exudates and buds which has different
      biological properties such as anti-hyperglycemia. In attention to better
      performance of nanoparticles in treatment, we synthesized propolis nanoparticles
      (PNP) and analyzed their physicochemical properties by dynamic light scattering
      (DLS), scanning electron microscopy (SEM), Zeta potential and FTIR analyses.
      Then, the structural changes of human hemoglobin (Hb), in three different forms
      of free, glycated and fructated Hb upon interaction with PNP at two temperatures
      of 25 and 37 degrees C were investigated using fluorescence and far-UV circular
      dichoroism (CD) spectroscopic techniques. The size distribution of PNP was less
      than 100nm. Fluorescence results indicated that PNP have a strong ability in
      quenching the intrinsic fluorescence of different forms of Hb. The binding
      constants, number of binding sites and thermodynamic parameters of these
      interactions were calculated and compare to each other. The Gibbs free energy
      values for glycated and fructated Hb with PNP were calculated-1635 and 1065J/mol,
      respectively at 25 degrees C which indicates that interaction of Hb with PNP is
      more favorable than interaction of GHb with PNP. CD spectra indicated that PNP
      lead to no significant changes in the secondary structure of different types of
      Hb. So, PNP as a natural product, due to antioxidant properties and lack of
      toxicity, can be used in the drug delivery system.

PMID- 29175522
TI  - Characterization of cellulosic paper coated with chitosan-zinc oxide
      nanocomposite containing nisin and its application in packaging of UF cheese.
AB  - A new antimicrobial bilayer film was developed using chitosan, cellulose, and
      nisin. Chitosan solution containing nisin (500 and 1000MUg/mL) was prepared by
      sol-gel method and then the solution was coated on cellulose paper by dip coating
      method. A chitosan-cellulose film without antimicrobial had no inhibitory effect
      on Listeria monocytogenes, whereas, the incorporation of nisin made a significant
      increase (P<0.05) in antimicrobial characteristics of the films. Moreover, no
      significant differences were shown on antimicrobial activity of developed films
      during the storage at 4 degrees C for one month. However, the addition of nisin
      showed a significant increase in the swelling index and solubility of bilayer
      film. Scanning electron microscope images revealed a uniform coating of chitosan
      solution on cellulose paper. The FTIR analysis also confirmed successful
      introducing and binding of the nisin in double layer film. Films with 1000MUg/mL
      of nisin completely inactivated the initial (~5log10 CFU/g) counts of L.
      monocytogenes on the surface of Ultra-filter white cheese after storage at 4
      degrees C for 14 days. We concluded that nanocomposite film of chitosan-cellulose
      containing nisin has novel antibacterial activity and can be used for packaging
      in cheese.

PMID- 29175523
TI  - Improved mechanical properties and thermal-stability of collagen fiber based film
      by crosslinking with casein, keratin or SPI: Effect of crosslinking process and
      concentrations of proteins.
AB  - This study utilized three different thermo-stable proteins of casein, keratin and
      soy protein isolate (SPI) to improve the thermal stabilities and mechanical
      properties of collagen fiber films using transglutaminase (TGase) crosslinking.
      The crosslinking greatly enhanced the thermal- stability of collagen fiber films,
      especially that of the collagen fiber crosslinking with 50% casein composite
      films, judged from thermogravimetric analysis (TGA). Furthermore, the TGase
      treatment improved the mechanical properties of the collagen fiber films interms
      of tensile strength (TS) and elongation at break (EAB). Importantly, a prominent
      improvement in EAB at wet and heated state was noted when collagen fiber
      crosslinked with 50% keratin or 50% casein, respectively. Moreover, different
      addition patterns of proteins in the collagen fiber films offered altered
      morphology as observed by scanning electron microscopy (SEM). Meanwhile, the
      conformational changes of the films revealed by fourier transform infrared
      spectroscopy (FTIR) confirmed a greater stabilization of film in the group of
      collagen fiber crosslinking with other proteins. In conclusion, the crosslinking
      action induced by TGase between collagen fiber and higher thermo-stable proteins
      promoted heat-resistance and mechanical properties of collagen fiber based film.

PMID- 29175524
TI  - Characterization of L-asparaginase from marine-derived Aspergillus niger AKV
      MKBU, its antiproliferative activity and bench scale production using industrial
      waste.
AB  - L-asparaginase (LA), an enzyme with anticancer activities, produced by marine
      derived Aspergillus niger was subjected to purification and characterization. The
      purified enzyme was observed to have molecular weight ~90KDa. The enzyme retained
      activity over a wide range of pH, i.e. pH 4-10. The enzyme was quite stable in
      temperature range 20-40 degrees C. Tween 80 and Triton X-100 were observed to
      enhance LA activity while inhibition of LA activity was observed in presence of
      heavy metals. The values for Km was found to be 0.8141 mM and Vmax was
      6.228MUM/mg/min. The enzyme exhibited noteworthy antiproliferative activity
      against various cancer cell lines tested. Successful bench scale production (in
      5L bioreacator) of LA using groundnut oil cake as low cost substrate has also
      been carried out.

PMID- 29175525
TI  - Crystallinity and lowering band gap induced visible light photocatalytic activity
      of TiO2/CS (Chitosan) nanocomposites.
AB  - The inhibition of electrons-holes recombination and enhancement of visible light
      photocatalytic activity were accomplished by the synthesized TiO2/CS
      nanocomposites system. In this present work, the different weight ratio of TiO2
      and chitosan (75:25, 50:50 and 25:75) nanocomposites were synthesized via two
      step method. After that, the existing functional groups, size and structure of
      the nanocomposites system were characterized via FT-IR, TEM and XRD measurements.
      The band gap of the prepared materials and its excitation and emission spectra
      were elevated through UV-vis and PL analyses. Moreover, the MO and MB degradation
      capability of the synthesized TiO2/CS nanocomposites was optimized, and the
      outcomes are described in detail.

PMID- 29175526
TI  - Calcium-dependent interaction of monomeric S100P protein with serum albumin.
AB  - S100 proteins are multifunctional (intra/extra)cellular mostly dimeric calcium
      binding proteins engaged into numerous diseases. We have found that monomeric
      recombinant human S100P protein interacts with intact human serum albumin (HSA)
      in excess of calcium ions with equilibrium dissociation constant of 25-50nM, as
      evidenced by surface plasmon resonance spectroscopy and fluorescent titration by
      HSA of S100P labelled by fluorescein isothiocyanate. Calcium removal or S100P
      dimerization abolish the S100P-HSA interaction. The interaction is selective,
      since S100P does not bind bovine serum albumin and monomeric human S100B lacks
      interaction with HSA. In vitro glycation of HSA disables its binding to S100P.
      The revealed selective and highly specific conformation-dependent interaction
      between S100P and HSA shows that functional properties of monomeric and dimeric
      forms of S100 proteins are different, and raises concerns on validity of cell
      based assays and animal models used for studies of (patho)physiological roles of
      extracellular S100 proteins.

PMID- 29175527
TI  - Factors That Contribute to Indeterminate Results From the QuantiFERON-TB Gold In
      Tube Test in Patients With Inflammatory Bowel Disease.
AB  - BACKGROUND & AIMS: The QuantiFERON-Tuberculosis Gold In-Tube (QFT-GIT) (QIAGEN
      Group, Hilden, Germany) test is widely used to screen for latent Mycobacterium
      tuberculosis infection in patients with inflammatory bowel diseases (IBD) before
      treatment with a tumor necrosis factor antagonist. The test frequently produces
      indeterminate results, prompting additional testing. We evaluated factors
      associated with indeterminate results from the QFT-GIT test among patients with
      IBD. METHODS: We conducted a case-control study among eligible adults with QFT
      GIT test results and a concomitant diagnosis of IBD receiving care at a tertiary
      referral center from 2011 through 2013. We compared patients with IBD with
      indeterminate and determinate (positive or negative) results from the QFT-GIT
      test. We collected data on patient demographics, clinical features, laboratory
      parameters, and medication use from medical charts. We calculated odds ratios
      (OR) and 95% CIs using multivariate logistic regression models. RESULTS: A total
      of 400 patients with IBD (265 Crohn's disease and 135 ulcerative colitis) were
      included in the final analyses. Indeterminate results were noted in 11.5% of
      patients. At the time of testing, a higher proportion of patients with
      indeterminate results from the QFT-GIT test were on systemic corticosteroid
      therapy (60.9% vs 30.5% of patients with conclusive test results; P < .001), had
      levels of C-reactive protein above 0.8 mg (62.2% vs 39.9% of patients with clear
      test results; P = .005), had an erythrocyte sedimentation rate above 15 mm/h
      (55.6% vs 35.8% of patients with clear test results; P = .01), had serum levels
      of albumin below 3.5 g/dL (33.3% vs 6.3% of patients with clear test results; P <
      .001), and had low levels of hemoglobin (52.2% vs 28.3% of patients with clear
      test results; P = .001). In multivariable analysis, corticosteroid use (adjusted
      OR, 2.92; 95% CI, 1.44-5.88; P = .003) and serum levels of albumin below 3.5 g/dL
      (adjusted OR, 3.62; 95% CI, 1.36-9.60; P = .009) were independently associated
      with increased risk of indeterminate QFT-GIT test results. We did not identify a
      dose-related effect with corticosteroid therapy and the odds of indeterminate QFT
      GIT test results. CONCLUSIONS: In a case-control study of patients with IBD, we
      associated systemic corticosteroid therapy and low levels of albumin with an
      increased likelihood of having indeterminate QFT-GIT test result.

PMID- 29175529
TI  - Thyroid hormone receptors and ligands, tissue distribution and sexual behavior.

PMID- 29175528
TI  - Excellent Outcomes of Liver Transplantation Following Down-Staging of
      Hepatocellular Carcinoma to Within Milan Criteria: A Multicenter Study.
AB  - BACKGROUND & AIMS: Single-center studies have reported excellent outcomes of
      patients who underwent liver transplantation for hepatocellular carcinoma (HCC)
      after successful down-staging (reduction of tumor burden with local-regional
      therapy), but multi-center studies are lacking. We performed a multi-center
      study, applying a uniform down-staging protocol, to assess outcomes of liver
      transplantation and performed an intention to treat analysis. We analyzed factors
      associated with treatment failure, defined as dropout from the liver transplant
      waitlist due to tumor progression, liver-related death without transplant, or
      recurrence of HCC after transplant. METHODS: We performed a retrospective multi
      center study of 187 consecutive adults with HCC enrolled in the down-staging
      protocol at 3 liver transplant centers in California (Region 5), from 2002
      through 2012. All patients underwent abdominal imaging 1 month after each local
      regional treatment, and at a minimum of once every 3 months. The primary outcome
      was probability of treatment failure. RESULTS: Liver transplantation was
      performed after successful down staging in 109 patients (58%). Tumor explant from
      only 1 patient had poorly differentiated grade and 7 (6.4%) had vascular
      invasion. Based on Kaplan-Meier analysis of data collected a median 4.3 years
      after liver transplantation, 95% of patients would survive 1 year and 80% of
      patients would survive 5 years; probabilities of recurrence-free survival were
      95% and 87%, respectively. There were no center-specific differences in survival
      in the intention to treat analysis (P = .62), in survival after liver
      transplantation (P = .95), or in recurrence of HCC (P = .99). Patients were
      removed from the liver transplantation waitlist due to tumor progression in (n =
      59; 32%) or liver-related death without liver transplantation (n = 9; 5%).
      Factors associated with treatment failure, based on multivariable analysis, were
      pre-treatment levels of alpha-fetoprotein (AFP) >1000 ng/mL (hazard ratio, 3.3; P
      < .001) and Child Pugh class B or C (hazard ratio, 1.6; P < .001). The
      probability of treatment failure at 2 years from the first down-staging procedure
      was 100% for patients with levels of AFP >1000 and Child Pugh class B or C vs
      29.4% for patients with neither risk factor (P < .001). CONCLUSIONS: In a
      retrospective, multi-center study on HCC down staging under a uniform protocol,
      we found patients to have excellent outcomes following liver transplantation,
      with no center-specific effects. Our findings support application of the down
      staging protocol on a broader scale. Patients with Child Pugh class B or C and
      AFP >1000 are unlikely to benefit from down staging.

PMID- 29175530
TI  - Increased tolerance of Beauveria bassiana and Metarhizium anisopliae conidia to
      high temperature provided by oil-based formulations.
AB  - The influence of the temperature of aqueous conidial sprays on conidial viability
      and virulence against Diatraea saccharalis was evaluated for pure conidia, rice +
      fungus (technical concentrates) and oil-based formulations of Beauveria bassiana
      s.s. and Metarhizium anisopliae s.s. under laboratory conditions. The fungal
      preparations were suspended in water and maintained at 26  degrees C, 36  degrees
      C and 46  degrees C for one, four and six hours. Conidial viability was
      determined by plating aliquots of each suspension onto PDA medium followed by
      incubation for 20-22 h and observing for viable conidia (germ tubes longer than
      diameter of conidia). Fungal virulence was determined by spraying suspensions
      onto third-instar larvae of D. saccharalis. In general, germination and
      virulence, particularly for unformulated conidia, were negatively affected by
      increases in water temperature and exposure time in suspension. However, the
      decrease in conidial viability in the oil-in-water emulsion was less than 7% for
      both species after 6 h of exposure at 36  degrees C, in contrast to reductions of
      7-21% and 28-60% for the oil-free suspensions of B. bassiana and M. anisopliae,
      respectively. For the sprays of conidia in an oil-in-water emulsion previously
      exposed to elevated water temperatures for longer periods, the levels of insect
      mortality were higher than those of pure conidia or technical concentrates under
      identical conditions. Our results indicate that emulsifiable oil-based
      formulations can protect the conidia of both species of fungi from the adverse
      effects of high water temperatures before spraying in the field.

PMID- 29175531
TI  - Olfactory cues play a significant role in removing fungus from the body surface
      of Drosophila melanogaster.
AB  - Many insects and Dipterans in particular are known to spend considerable time
      grooming, but whether these behaviors actually are able to remove pathogenic
      fungal conidia is less clear. In this study, we examined whether grooming serves
      to protect flies by reducing the risk of fungal infection in Drosophila
      melanogaster. First, we confirmed that fungi were removed by grooming.
      Entomopathogenic, opportunistic, and plant pathogenic fungi were applied on the
      body surface of the flies. To estimate grooming efficiency, the number of removal
      conidia through grooming was quantified and we successfully demonstrated that
      flies remove fungal conidia from their body surfaces via grooming behavior.
      Second, the roles of gustatory and olfactory signals in fungus removal were
      examined. The wildtype fly Canton-S, the taste deficiency mutant poxn 70, and the
      olfactory deficiency mutant orco1 were used in the tests. Comparisons between
      Canton-S and poxn 70 flies indicated that gustatory signals do not have a
      significant role in fungal removal via grooming behavior in D. melanogaster. In
      contrast, the efficiency of conidia removal in orco1 flies was drastically
      decreased. Consequently, this study indicated that flies rely on mechanical
      stimulus for the induction of grooming and olfaction for more detailed removal.

PMID- 29175532
TI  - Mitochondrial dynamics tracking with iridium(III) complexes.
AB  - Since the discovery of mitochondrial dynamics, demand for dyes able to track this
      process has been a great. In contrast to static imaging, dynamic tracking
      requires superior photostability, low cytotoxicity and high resistance to the
      loss of mitochondrial membrane potential as well as appreciable tolerance to
      environmental changes. Recently, a variety of phosphorescent Ir(III) complexes
      have been found to localize in mitochondria and their applications as
      mitochondrial dynamics trackers have been assessed in cell monolayers, 3D MCSs
      and live animals. The examples presented here demonstrate that Ir(III) complexes
      constitute ideal candidates to meet the challenges of this topic.

PMID- 29175533
TI  - Large-scale evaluation of a rapid diagnostic test for diarrhea caused by
      enterotoxigenic Escherichia coli targeting the heat-labile toxin.
AB  - We standardized an immunochromatographic test (IC) for heat-labile toxin I (LT-I)
      detection using LT-I antibodies and a specific platform containing the apparatus
      for application, assembly and cutting. IC detected as little as 62.5ng/mL of
      purified LT-I toxin and presented 91% sensitivity, 99.5% specificity and 96.0%
      accuracy, thereby proving to be an excellent point-of-care test for the diagnosis
      of enterotoxigenic E. coli infection in low-income countries.

PMID- 29175534
TI  - A highly efficient Agrobacterium tumefaciens-mediated transformation system for
      the postharvest pathogen Penicillium digitatum using DsRed and GFP to visualize
      citrus host colonization.
AB  - Penicillium digitatum is a major postharvest pathogen of citrus crops. This
      fungus broadly spreads worldwide and causes green mold disease, which results in
      severe losses for citrus production. Understanding of the citrus infection by P.
      digitatum may help develop effective strategies for controlling this pathogen. In
      this study, we have characterized a virulent strain of P. digitatum isolated in
      Vietnam and established a highly efficient Agrobacterium tumefaciens-mediated
      transformation (ATMT) system for this fungal strain with two newly constructed
      binary vectors. These binary vectors harbor dominant selectable markers for
      hygromycin or nourseothricin resistance, and expression cassettes for the red
      fluorescent protein (DsRed) or the green fluorescent protein (GFP), respectively.
      Using the established ATMT system, the transformation efficiency of the
      Vietnamese strain could reach a very high yield of 1240+/-165 transformants per
      106 spores. Interestingly, we found that GFP is much better than DsRed for in
      situ visualization of citrus fruit colonization by the fungus. Additionally, we
      showed that the transformation system can also be used to generate T-DNA
      insertion mutants for screening non-pathogenic or less virulent strains. Our work
      provides a new platform including a virulent tropical strain of P. digitatum, an
      optimized ATMT method and two newly constructed binary vectors for investigation
      of the postharvest pathogen. This platform will help develop strategies to
      dissect molecular mechanisms of host-pathogen interactions in more detail as well
      as to identify potential genes of pathogenicity by either insertional mutagenesis
      or gene disruption in this important pathogenic fungus.

PMID- 29175535
TI  - Application of prognostic scores in the STOPAH trial: Discriminant function is no
      longer the optimal scoring system in alcoholic hepatitis.
AB  - BACKGROUND & AIMS: 'Static' prognostic models in alcoholic hepatitis, using data
      from a single time point, include the discriminant function (DF), Glasgow
      alcoholic hepatitis score (GAHS), the age, serum bilirubin, international
      normalized ratio and serum creatinine (ABIC) score and the model of end-stage
      liver disease (MELD). 'Dynamic' scores, incorporating evolution of bilirubin at
      seven days, include the Lille score. The aim of this study was to assess these
      scores' performance in patients from the STOPAH trial. METHODS: Predictive
      performance of scores was assessed by area under the receiver operating curve
      (AUC). The effect of different therapeutic strategies upon survival was assessed
      by Kaplan-Meier analysis and tested using the log-rank test. RESULTS: A total of
      1,068 patients were studied. The AUCs for the DF were significantly lower than
      for MELD, ABIC and GAHS for both 28- and 90-day outcomes: 90-day values were
      0.670, 0.704, 0.726 and 0.713, respectively. 'Dynamic' scores and change in
      'static' scores by Day 7 had similar AUCs. Patients with consistently low
      'static' scores had low 28-day mortalities that were not improved with
      prednisolone (MELD <25: 8.6%; ABIC <6.71: 6.6%; GAHS <9: 5.9%). In patients with
      high 'static' scores without gastrointestinal bleeding or sepsis, prednisolone
      reduced 28-day mortality (MELD: 22.2% vs. 28.9%, p = 0.13; ABIC 14.6% vs. 21%, p
      = 0.02; GAHS 21% vs. 29.3%, p = 0.04). Overall mortality from treating all
      patients with a DF >=32 and Lille assessment (90-day mortality 26.8%) was greater
      than combining newer 'static' and 'dynamic' scores (90-day mortality: MELD/Lille
      21.8%; ABIC/Lille 23.7%; GAHS/Lille 20.6%). CONCLUSION: MELD, ABIC and GAHS are
      superior to the DF in alcoholic hepatitis. Consistently low scores have a
      favourable outcome not improved with prednisolone. Combined baseline 'static' and
      Day 7 scores reduce the number of patients exposed to corticosteroids and improve
      90-day outcome. LAY SUMMARY: Alcoholic hepatitis is a life-threatening condition.
      Several scores exist to determine the outcome of these patients as well as to
      identify those who may benefit from treatment. This study looked at the
      performance of existing scores in patients who had been recruited to the largest
      alcoholic hepatitis clinical trial: STOPAH. 'Static' scores are calculable at the
      start of assessment. The three newer static scores (ABIC, GAHS and MELD) were
      shown to be superior to the oldest score (DF). ABIC and GAHS could also identify
      patients who had a survival benefit 28 days after starting prednisolone
      treatment. 'Dynamic' scores relate to the change in disease over the first week
      of treatment. Combination of the 'static' scores 'with the 'dynamic' scores or
      change in 'static' scores allowed identification of patients who could benefit
      from prednisolone up to 90 days.

PMID- 29175536
TI  - Stomach reduction or gastric bypass as risk factor for treatment failure after
      DAA therapy for hepatitis C?

PMID- 29175537
TI  - Vitrification of human pronuclear oocytes by direct plunging into cooling agent:
      Non sterile liquid nitrogen vs. sterile liquid air.
AB  - In fact, a full sterilization of commercially-produced liquid nitrogen
      contaminated with different pathogens is not possible. The aim of this study was
      to compare the viability of human pronuclear oocytes subjected to cooling by
      direct submerging of open carrier in liquid nitrogen versus submerging in clean
      liquid air (aseptic system). One- and three-pronuclei stage embryos (n = 444)
      were cryopreserved by direct plunging into liquid nitrogen (vitrified) in
      ethylene glycol (15%), dimethylsulphoxide (15%) and 0.2M sucrose. Oocytes were
      exposed in 20, 33, 50 and 100% vitrification solution for 2, 1 and 1 min, and 30
      50 s, respectively at room temperature. Then first part of oocytes (n = 225) were
      directly plunged into liquid nitrogen, and second part of oocytes (n = 219) into
      liquid air. Oocytes were thawed rapidly at a speed of 20,000  degrees C/min and
      then subsequently were placed into a graded series of sucrose solutions (0.5,
      0.25, 0.12 and 0.06M) at 2.5 min intervals and cultured in vitro for 3 days. In
      both groups, the rate of high-quality embryos (Grade 6A: 6 blastomeres, no
      fragmentation; Grade 8A: 8 blastomeres, no fragmentation; Grade 8A compacting: 8
      blastomeres, beginning of compacting) was noted. The rates of high-quality
      embryos developed from one-pronuclear oocytes vitrified by cooling in liquid
      nitrogen and liquid air were: 39.4% +/- 0.6 and 38.7% +/- 0.8, respectively (P >
      0.1). These rates for three-pronuclear oocytes were: 45.8 +/- 0.8% and 52.0 +/-
      0.7%, respectively (P < 0.05). In conclusion, vitrification by direct submerging
      of oocytes in clean liquid air (aseptic system) is a good alternative for using
      of not sterile liquid nitrogen.

PMID- 29175540
TI  - The Effect of Family Assistance to Wake Children with Monosymptomatic Enuresis in
      Alarm Therapy: A Pilot Study.
AB  - PURPOSE: Alarm therapy is widely used as first line treatment for nocturnal
      enuresis. However, some children do not wake when nocturnal urination activates
      the alarm. It is currently unclear whether waking the child when the alarm is
      activated improves the efficacy of alarm therapy. In this study we investigated
      the efficacy of alarm therapy for nocturnal enuresis when children do not wake in
      response to the sound and their parents do not wake them. MATERIALS AND METHODS:
      Detailed information regarding incontinence was retrospectively obtained from 78
      of 112 patients who underwent alarm therapy between 2006 and 2016, and completed
      a questionnaire and a 14-day bladder diary. The enrolled patients were divided
      into 2 groups. In the family assisted group (44) the children were awakened by
      family members when the alarm sounded. In the alarm control group (34) the
      children were self-responsible for waking to the alarm. The groups were compared
      to investigate differences at 16 weeks after alarm therapy began. The efficacy
      rate was calculated using the International Children's Continence Society
      criteria. RESULTS: The efficacy was similar between the groups. Full response and
      partial response were observed in 36.4% and 20.5% of patients in the family
      assisted group, and 26.5% and 29.4% of patients in the alarm control group (p =
      1.00), respectively. There was no significant difference in the percentage of
      children who woke spontaneously to the alarm in the 2 groups (56.7% and 64.0%,
      respectively). CONCLUSIONS: Family assisted alarm therapy and self-responsible
      alarm therapy are equally efficacious in the treatment of childhood nocturnal
      enuresis.

PMID- 29175541
TI  - A Randomized Comparative Study Evaluating Various Cough Stress Tests and 24-Hour
      Pad Test with Urodynamics in the Diagnosis of Stress Urinary Incontinence.
AB  - PURPOSE: The cough stress test is a common and accepted tool to evaluate stress
      urinary incontinence but there is no agreement on how the test should be
      performed. We assessed the diagnostic ability of different cough stress tests
      performed when varying patient position and bladder volume using urodynamic
      stress urinary incontinence as the gold standard. The 24-hour pad test was also
      evaluated. MATERIALS AND METHODS: We recruited women who presented to specialty
      outpatient clinics with the complaint of urinary incontinence and who were
      recommended to undergo urodynamic testing. A total of 140 patients were
      randomized to 4 cough stress test groups, including group 1-a comfortably full
      bladder, group 2-an empty bladder, group 3- a bladder infused with 200 cc saline
      and group 4-a bladder filled to half functional capacity. The sequence of
      standing and sitting was randomly assigned. The groups were compared by 1-way
      ANOVA or the generalized Fisher exact test. The kappa statistic was used to
      evaluate agreement between the sitting and standing positions. The 95% CIs of
      sensitivity and specificity were calculated using the Wilson method. ROC analysis
      was done to evaluate the performance of the 24-hour pad test. RESULTS: The cough
      stress test performed with a bladder filled to half functional capacity was the
      best performing test with 83% sensitivity and 90% specificity. There was no
      statistically significant evidence that the sensitivity or specificity of 1 cough
      stress test differed from that of the others. The pad test had no significant
      predictive ability to diagnose urodynamic stress urinary incontinence (AUC 0.60,
      p = 0.08). CONCLUSIONS: Cough stress tests were accurate to diagnose urodynamic
      stress urinary incontinence. The 24-hour pad test was not predictive of
      urodynamic stress urinary incontinence and not helpful when used in conjunction
      with the cough stress test.

PMID- 29175538
TI  - White matter structural connectivity and episodic memory in early childhood.
AB  - Episodic memory undergoes dramatic improvement in early childhood; the reason for
      this is poorly understood. In adults, episodic memory relies on a distributed
      neural network. Key brain regions that supporting these processes include the
      hippocampus, portions of the parietal cortex, and portions of prefrontal cortex,
      each of which shows different developmental profiles. Here we asked whether
      developmental differences in the axonal pathways connecting these regions may
      account for the robust gains in episodic memory in young children. Using
      diffusion weighted imaging, we examined whether white matter connectivity between
      brain regions implicated in episodic memory differed with age, and were
      associated with memory performance differences in 4- and 6-year-old children.
      Results revealed that white matter connecting the hippocampus to the inferior
      parietal lobule significantly predicted children's performance on episodic memory
      tasks. In contrast, variation in the white matter connecting the hippocampus to
      the medial prefrontal cortex did not relate to memory performance. These findings
      suggest that structural connectivity between the hippocampus and lateral parietal
      regions is relevant to the development of episodic memory.

PMID- 29175539
TI  - Intact perceptual ability, but impaired familiarity judgment, after neonatal
      perirhinal lesions in rhesus macaques.
AB  - The perirhinal cortex is known to support high-level perceptual abilities as well
      as familiarity judgments that may affect recognition memory. We tested whether
      poor perceptual abilities or a loss of familiarity judgment contributed to the
      recognition memory impairments reported earlier in monkeys with PRh lesions
      received in infancy (Neo-PRh) (Weiss and Bachevalier, 2016; Zeamer et al., 2015).
      Perceptual abilities were assessed using a version of the Visual Paired
      Comparison task with black&white (B&W) stimuli, and familiarity judgments were
      assessed using the Constant Negative task requiring repeated familiarization
      exposures. Adult monkeys with Neo-PRh lesions were able to recognize B&W stimuli
      after short delays, suggesting that their perceptual abilities were within the
      range of control animals. However, the same Neo-PRh monkeys were slower to
      acquire the Constant Negative task, requiring more exposures to objects before
      judging them as familiar compared to control animals. Taken together, the data
      help to account for the differential patterns of functional compensation on
      previously reported recognition tasks following neonatal versus adult-onset PRh
      lesions, and provide further support to the view that the PRh is involved in
      familiarity processes.

PMID- 29175542
TI  - Defining a Cohort that May Not Require Repeat Prostate Biopsy Based on PCA3 Score
      and Magnetic Resonance Imaging: The Dual Negative Effect.
AB  - PURPOSE: Prostate cancer over diagnosis and overtreatment are concerns for
      clinicians and policy makers. Multiparametric magnetic resonance imaging and the
      PCA3 (prostate cancer antigen 3) urine test select for clinically significant
      cases. We explored how well the tests performed together with previous biopsies.
      MATERIALS AND METHODS: In accordance with ethics committee approval we collected
      clinicopathological data on all patients in whom a PCA3 test was done from
      January 2011 to June 2016. This included patients on active surveillance for low
      risk prostate cancer and those without prostate cancer who had previous negative
      biopsies and suspicion of occult disease. We explored whether age, prostate
      specific antigen, PCA3 score, multiparametric magnetic resonance imaging, digital
      rectal examination, family history and prostate size would predict clinically
      significant prostate cancer on repeat biopsy. The negative predictive value of
      multiparametric magnetic resonance imaging and PCA3 score was calculated.
      RESULTS: A total of 470 patients were included in study. The PCA3 score was
      abnormal at 35 or greater in 32.5% of cases. In the multivariate model including
      154 men only age (OR 1.08, 95% CI 1.01-1.16), multiparametric magnetic resonance
      imaging PI-RADSTM (Prostate Imaging-Reporting and Data System) score 4 (OR 16.6,
      95% CI 3.9-70.0) or 5 (OR 28.3, 95% CI 5.7-138) and PCA3 score (OR 2.9, 95% CI
      1.0-8.8) predicted clinically significant cancer on biopsy. No patient with
      negative multiparametric magnetic resonance imaging and a normal PCA3 score had
      clinically significant prostate cancer on biopsy for a negative predictive value
      of 100% (p <0.0001). CONCLUSIONS: In patients with dual negative tests
      (multiparametric magnetic resonance imaging and PCA3 score) clinically
      significant prostate cancer was never found on biopsy, which may be unnecessary
      in this group. This study was limited by its retrospective design, selection bias
      and lack of cost-effectiveness data.

PMID- 29175543
TI  - High mobility group box-1 (HMGB1) is increased in injured mouse spinal cord and
      can elicit neurotoxic inflammation.
AB  - Inflammation is a ubiquitous but poorly understood consequence of spinal cord
      injury (SCI). The mechanisms controlling this response are unclear but culminate
      in the sequential activation of resident and recruited immune cells.
      Collectively, these cells can exert divergent effects on cell survival and tissue
      repair. HMGB1 is a ubiquitously expressed DNA binding protein and also a potent
      inflammatory stimulus. Necrotic cells release HGMB1, but HMGB1 also is actively
      secreted by inflammatory macrophages. A goal of this study was to quantify spatio
      temporal patterns of cellular HMGB1 expression in a controlled mouse model of
      experimental SCI then determine the effects of HMGB1 on post-SCI
      neuroinflammation and recovery of function. We documented SCI-induced changes in
      nuclear and cytoplasmic distribution of HMGB1 in various cell types after SCI.
      The data reveal a time-dependent increase in HMGB1 mRNA and protein with protein
      reaching maximal levels 24-72 h post-injury then declining toward baseline 14-28
      days post-SCI. Although most cells expressed nuclear HMGB1, reduced nuclear
      labeling with increased cytoplasmic expression was found in a subset of CNS
      macrophages suggesting that those cells begin to secrete HMGB1 at the injury
      site. In vitro data indicate that extracelluar HMGB1 helps promote the
      development of macrophages with a neurotoxic phenotype. The ability of HMGB1 to
      elicit neurotoxic macrophage functions was confirmed in vivo; 72 h after
      injecting 500 ng of recombinant HMGB1 into intact spinal cord ventral horn,
      inflammatory CNS macrophages co-localized with focal areas of neuronal killing.
      However, attempts to confer neuroprotection after SCI by blocking HMGB1 with a
      neutralizing antibody were unsuccessful. Collectively, these data implicate HMGB1
      as a novel regulator of post-SCI inflammation and suggest that inhibition of
      HMGB1 could be a novel therapeutic target after SCI. Future studies will need to
      identify better methods to deliver optimal concentrations of HMGB1 antagonists to
      the injured spinal cord.

PMID- 29175544
TI  - Comparative systemic analysis of the cellular growth of leaves and roots in
      controlled conditions.
AB  - The comparative cytological analysis of the leaf/root growth of Lolium
      multiflorum has been performed. It revealed differences of the mentioned
      above/under-ground organs that express the whole plant's polarity. To perform
      accurate and simultaneous growth comparison a climatic-hydroponics system has
      been implemented. A sharp increase in the epidermis cell length of the leaf
      meristem has been detected for the first time. It allows the proposal of a new
      way to demarcate the boundary of the meristem and suggests a lengthed leaf
      meristem, that is 4 times longer than the root meristem. As the cell cycle
      duration in leaves and roots is similar, the prolonged leaf meristem and a higher
      leaf growth rate could be determined by the longer life span of cells in
      meristem, resulting in more cell cycles. The prolonged meristem provides a
      significantly higher leaf growth rate, ensuring a functional balance with roots.
      The elongation zone of the roots is significantly shorter than in leaves, which
      is caused by the larger relative root elongation rate and the slower meristemic
      root growth rate. The novelty formulated, i.e., the prolonged leaf meristem,
      opens theoretical perspectives in longitudinal zonation, in finding molecular
      markers and provides practical significance for the biology of productivity.

PMID- 29175545
TI  - In vivo cytological and chemical analysis of Casparian strips using stimulated
      Raman scattering microscopy.
AB  - The Casparian strip, a barrier to the apoplastic movement of solutes from the
      cortex to the stele, is essential for the exclusion of salts, selective nutrient
      uptake, and many other processes. To date, extensive studies have focused on the
      physiological functions of endodermal Casparian strips. However, the chemical
      deposition nature of Casparian strips, as well as its relevance with respect to
      diffusion barrier functions, remains to be further elucidated. Here, we revealed
      three developmental stages of Casparian strips in maize primary roots using a
      traditional fluorescent staining method. Apoplastic permeability tests
      demonstrated that the barrier function of Casparian strips is largely related to
      their developmental stage and the pattern of lignin and suberin deposits. Fourier
      transform infrared (FTIR) analysis showed that the Casparian strips from the
      roots exhibited significant absorption bands characteristic of lignin and
      suberin, implying that the Casparian strips in maize primary roots consist
      largely of lignin and suberin. Furthermore, we developed a new method for label
      free, in vivo structural, and biochemical analysis of Casparian strips based on
      stimulated Raman scattering (SRS) microscopy. Using SRS microscopy, we found that
      lignin and suberin accumulate simultaneously during the Casparian strip formation
      process. Based on these results, we propose a potential application of SRS for
      the chemical composition analysis of plant Casparian strips in situ.

PMID- 29175547
TI  - ZTE MRI in high magnetic field as a time effective 3D imaging technique for
      monitoring water ingress in porous rocks at sub-millimetre resolution.
AB  - Zero echo time magnetic resonance imaging (ZTE MRI) at 9.4T was used to assess
      the local distribution of water in dolomite rocks under different saturation
      conditions. The results were compared with the industry standard Single Point
      Imaging (SPI) at 0.6T. 3D maps of the local amount of water saturating
      heterogeneous rock were obtained from the imaging data, and correlated with the
      corresponding structural images from high resolution micro-CT (MUCT). The method
      can be applicable in the investigation of spatial kinetics of water saturation
      processes in porous, heterogeneous rocks where imaging methods based on spin
      echo, such as RARE, have failed due to short T2, while SPI is often impractical
      due to its long acquisition time.

PMID- 29175546
TI  - How many pygmy marmoset (Cebuella Gray, 1870) species are there? A taxonomic re
      appraisal based on new molecular evidence.
AB  - The pygmy marmoset, Cebuella pygmaea, the smallest of the New World monkeys, has
      one of the largest geographical distributions of the Amazonian primates. Two
      forms have been recognized: Cebuella pygmaea pygmaea (Spix, 1823), and C. p.
      niveiventris Lonnberg, 1940. In this study, we investigated if the separation of
      pygmy marmosets into these two clades can be corroborated by molecular data. We
      also examine and compare coloration of the pelage in light of the new molecular
      results. We analyzed the mtDNA cytochrome b gene and, for the first time for any
      Neotropical primate, we used a reduced representation genome sequencing approach
      (ddRADseq) to obtain data for recently collected, geographically representative
      samples from the Rio Japura, a northern tributary of the Rio Solimoes and from
      the Javari, Jutai, Jurua, Madeira and Purus river basins, all tributaries south
      of the Solimoes. We estimated phylogenies and diversification times under both
      maximum likelihood and Bayesian inference criteria. Our analysis showed two
      highly supported clades, with intraclade divergences much smaller than interclade
      divergences, indicating two species of Cebuella: one from the Rio Japura and one
      to the south of Solimoes. The interpretation of our results in light of the
      current taxonomy is not trivial however. Lonnberg stated that the type of Spix's
      pygmy marmoset (type locality 'near Tabatinga') was obtained from the south of
      the Solimoes, and his description of the distinct niveiventris from Lago Ipixuna,
      south of the Solimoes and several hundred kilometres east of Tabatinga, was based
      on a comparison with specimens that he determined as typical pygmaea that were
      from the upper Rio Jurua (south of the Solimoes). As such it remains uncertain
      whether the name pygmaea should be applicable to the pygmy marmosets north of the
      Rio Solimoes (Tabatinga type locality) or south (near Tabatinga but across the
      Solimoes). Finally, our analysis of pelage coloration revealed three phenotypic
      forms: (1) south of the Rio Solimoes, (2) Eirunepe-Acre, upper Jurua basin; and
      (3) Japura. More samples from both sides of Solimoes in the region of Tabatinga
      will be necessary to ascertain the exact type locality for Spix's pygmaea and to
      resolve the current uncertainties surrounding pygmy marmoset taxonomy.

PMID- 29175548
TI  - Radiology report annotation using intelligent word embeddings: Applied to multi
      institutional chest CT cohort.
AB  - We proposed an unsupervised hybrid method - Intelligent Word Embedding (IWE) that
      combines neural embedding method with a semantic dictionary mapping technique for
      creating a dense vector representation of unstructured radiology reports. We
      applied IWE to generate embedding of chest CT radiology reports from two
      healthcare organizations and utilized the vector representations to semi-automate
      report categorization based on clinically relevant categorization related to the
      diagnosis of pulmonary embolism (PE). We benchmark the performance against a
      state-of-the-art rule-based tool, PeFinder and out-of-the-box word2vec. On the
      Stanford test set, the IWE model achieved average F1 score 0.97, whereas the
      PeFinder scored 0.9 and the original word2vec scored 0.94. On UPMC dataset, the
      IWE model's average F1 score was 0.94, when the PeFinder scored 0.92 and word2vec
      scored 0.85. The IWE model had lowest generalization error with highest F1
      scores. Of particular interest, the IWE model (trained on the Stanford dataset)
      outperformed PeFinder on the UPMC dataset which was used originally to tailor the
      PeFinder model.

PMID- 29175550
TI  - Molecular modeling study on resistance of WT/D473H SMO to antagonists LDE-225 and
      LEQ-506.
AB  - The smoothened (SMO) receptor, an essential signal transducer in the Hedgehog
      pathway, was targeted with antagonists to suppress the tumor. It is interesting
      that SMO D473H mutation confers resistance on inhibitor LDE-225 rather than LEQ
      506. In this paper, the binding modes of them against the wild type and mutant
      SMO receptors were identified to gain insights into the resistant and non
      resistant factors, based on a comprehensive protocol involving molecular docking,
      molecular dynamic simulations, free energy calculation and decomposition. A
      comparison of resistant LDE-225 and non-resistant LEQ-506 indicates that the
      volume of the binding cavity decreases seriously in the mutant complex with
      resistant LDE-225. In addition, the D473H mutation disrupts the hydrogen bond
      network with residues R400 and Q477, which results in the TM6 conformation
      inward. Owing to the absence of the hydrogen bond, residues R400 and Q477 make
      weak contributions to LDE-225. However, the D473H mutation along with TM6
      conformational change has no effect on non-resistant LEQ-506. Finally, the
      resistance ascribes to adverse interaction between the greater polarity of mutant
      residue H473 and the nonpolar phenmethyl of LDE-225. The elaborate insights into
      structural and energetic mechanism of drug resistance provide an effective
      strategy to design rationally non-resistant antagonists.

PMID- 29175549
TI  - Integrated analytical assets aid botanical authenticity and adulteration
      management.
AB  - This article reviews and develops a perspective for the meaning of authenticity
      in the context of quality assessment of botanical materials and the challenges
      associated with discerning adulterations vs. contaminations vs. impurities.
      Authentic botanicals are by definition non-adulterated, a mutually exclusive
      relationship that is confirmed through the application of a multilayered set of
      analytical methods designed to validate the (chemo)taxonomic identity of a
      botanical and certify that it is devoid of any adulteration. In practice, the
      ever-increasing sophistication in the process of intentional adulteration, as
      well as the growing number of botanicals entering the market, altogether
      necessitate a constant adaptation and reinforcement of authentication methods
      with new approaches, especially new technologies. This article summarizes the set
      of analytical methods - classical and contemporary - that can be employed in the
      authentication of botanicals. Particular emphasis is placed on the application of
      untargeted metabolomics and chemometrics. An NMR-based untargeted metabolomic
      model is proposed as a rapid, systematic, and complementary screening for the
      discrimination of authentic vs. potentially adulterated botanicals. Such
      analytical model can help advance the evaluation of botanical integrity in
      natural product research.

PMID- 29175551
TI  - Retrograded starch/pectin coated gellan gum-microparticles for oral
      administration of insulin: A technological platform for protection against
      enzymatic degradation and improvement of intestinal permeability.
AB  - Gellan gum microparticles coated with colon-specific films based on retrograded
      starch and pectin was developed for enhancing the oral release of insulin (INS).
      The system developed promoted an impressive protection of INS (80%) after 120 min
      of incubation with trypsin and alpha-chymotrypsin, while only 3% of free INS
      remained intact after the same time, possibility due to the calcium chelating
      activity of the polymers in inhibiting the proteolytic activity. In vitro INS
      release in media simulating the gastrointestinal portions revealed a pH-dependent
      behavior, as well as the significance of the coating in lowering the release
      rates in relation to their counterparts. The permeability of INS on Caco-2 cells
      monolayers and excised rat intestine were significantly improved, mainly due to
      the influence of the anionic polymers on tight junctions opening, along with the
      excellent mucoadhesive properties of the gellan gum. All these features together
      contributed greatly to the hypoglycemic effect observed after the oral
      administration of the INS-loaded MP in diabetic rats, with reduction of up to 51%
      of blood glucose levels. The important findings of this work should contribute to
      the advances about the search of alternatives for oral administration of INS.

PMID- 29175552
TI  - Long pentraxin 3: A novel multifaceted player in cancer.
AB  - Since its discovery in 1992, long pentraxin 3 (PTX3) has been characterized as
      soluble patter recognition receptor, a key player of the innate immunity arm with
      non-redundant functions in pathogen recognition and inflammatory responses. As a
      component of the extra-cellular matrix milieu, PTX3 has been implicated also in
      wound healing/tissue remodeling, cardiovascular diseases, fertility, and
      infectious diseases. Consequently, PTX3 levels in biological fluids have been
      proposed as a fluid-phase biomarker in different pathological conditions. In the
      last decade, experimental evidences have shown that PTX3 may exert a significant
      impact also on different aspects of cancer biology, including tumor onset,
      angiogenesis, metastatic dissemination and immune-modulation. However, it remains
      unclear whether PTX3 acts as a good cop or bad cop in cancer. In this review, we
      will summarize and discuss the scientific literature data focusing on the role of
      PTX3 in experimental and human tumors, including its putative translational
      implications.

PMID- 29175554
TI  - Determination of ZSTK474, a novel Pan PI3K inhibitor in mouse plasma by LC-MS/MS
      and its application to Pharmacokinetics.
AB  - ZSTK474, a promising novel anticancer molecule derived from s-triazine, found to
      have antitumor activities against different cancer cell lines. However, neither
      LCMS method nor pharmacokinetics of ZSTK474 has been reported till now. A
      sensitive, simple, short and specific liquid chromatography tandem mass
      spectrometry (LCMS/MS) method was developed for the quantification of ZSTK474 in
      mouse plasma accordance with the US Food and Drug Administration guidelines.
      Extraction of drug molecule was carried out using protein precipitation.
      Chromatographic analyte separation was achieved on Atlantis dC18 (4.6*50mm,
      3MUm). Composition of isocratic mobile phase consists of 90% acetonitrile and
      0.2% formic acid, at 0.7mL/min flow rate, having short 2.5min run time. Method
      development was validated and found to be linear over a dynamic range between 1.9
      1000ng/mL; having a correlation coefficient (r 2)>=0.9978. The analyte was found
      to be stable under short and long term storage conditions. LCMS/MS method
      developed was validated and found to be selective, reproducible, precise and
      accurate to quantify ZSTK474 in plasma samples, and first time successfully
      applied to pharmacokinetic studies. Pharmacokinetic data showed fast absorption
      attaining Cmax at 0.25h and half life (t1/2) 5.18h after oral administration of
      ZSTK474 at 20mg/kg in mouse.

PMID- 29175555
TI  - Pharmacokinetics of doxorubicin in glioblastoma multiforme following ultrasound
      Induced blood-brain barrier disruption as determined by microdialysis.
AB  - The goal of this study was to investigate the in vivo extracellular kinetics of
      doxorubicin (Dox) in glioblastoma multiforme (GBM)-bearing mice following focused
      ultrasound (FUS)-induced blood-brain barrier (BBB) disruption using
      microdialysis. An intracranial brain tumor model in NOD-scid mice using human
      brain GBM 8401 cells was used in this study. Prior to each sonication,
      simultaneous intravenous administration of Dox and microbubbles, and the Dox
      concentration in the brains was quantified by high performance liquid
      chromatography (HPLC). Drug administration with sonication elevated the tumor-to
      normal brain Dox ratio of the target tumors by about 2.35-fold compared with the
      control tumors. The mean peak concentration of Dox in the sonicated GBM dialysate
      was 10 times greater than without sonication, and the area under the
      concentration-time curve was 3.3 times greater. This study demonstrates that
      intracerebral microdialysis is an effective means of evaluating real-time target
      BBB transport profiles and offers the possibility of investigating the
      pharmacokinetics of drug delivery in the sonicated brain.

PMID- 29175556
TI  - Rapid and simple procedure for the determination of cathinones, amphetamine-like
      stimulants and other new psychoactive substances in blood and urine by GC-MS.
AB  - In the last few years an increasing number of new psychoactive substances (NPS),
      with different chemical structures (of which 37% are stimulants), have been
      released into the illicit drug market. Their detection and identification in
      biological samples is hence of great concern. The aim of this work was to develop
      a high-throughput and rapid method for the determination of different classes of
      stimulants (amphetamine-type stimulants, cathinones, phenethylamines and ketamine
      analogues) from blood and urine samples using GC-MS. The proposed method allows
      the almost simultaneous derivatization and extraction of analytes from biological
      samples in a very short time, by using hexyl chloroformate as derivatization
      agent. The extraction of analytes was performed by Dispersive Liquid Liquid
      Microextraction (DLLME), a very rapid, cheap and efficient extraction technique
      that employs microliter amounts of organic solvents. The chromatographic method
      allowed for the separation of 26 stimulants including positional isomers (3-MMC
      and 4-MMC). The method was validated on urine and blood samples with the ability
      to detect and quantify all analytes with satisfactory limits of detection (LODs)
      ranging between 1 and 10ng/mL, limits of quantification (LOQs) between 2 and
      50ng/mL, selectivity and linearity (5-1000ng/mL). The method was then applied to
      real samples from forensic cases, demonstrating its suitability for the screening
      of a wide number of stimulants in biological specimens.

PMID- 29175557
TI  - Meniscal repair: Technique.
AB  - Meniscal repair aims to achieve meniscal healing, avoiding the adverse effects of
      meniscectomy. Longitudinal vertical tears in a vascularized area are the
      reference indication. The technique generally uses hybrid all-inside implants.
      The outside-in technique has other indications in more anterior tears. Healing
      has been demonstrated on CT-arthrography and arthroscopy. Specific techniques
      have been developed for other pathological situations. Posterior meniscosynovial
      lesions in a context of chronic anterior laxity are identified by exploration of
      the posterior compartment, and fixed by all-inside hook suture. Horizontal
      lesions in young athletes can be treated by open meniscal suture. Radial tears,
      when deep, can be repaired. Root tears, when traumatic, can be treated by
      transosseous pullout reinsertion.

PMID- 29175553
TI  - The key role of extracellular vesicles in the metastatic process.
AB  - Extracellular vesicles (EVs), including exosomes, have a key role in the
      paracrine communication between organs and compartments. EVs shuttle virtually
      all types of biomolecules such as proteins, lipids, nucleic acids, metabolites
      and even pharmacological compounds. Their ability to transfer their biomolecular
      cargo into target cells enables EVs to play a key role in intercellular
      communication that can regulate cellular functions such as proliferation,
      apoptosis and migration. This has led to the emergence of EVs as a key player in
      tumor growth and metastasis through the formation of "tumor niches" in target
      organs. Recent data have also been shown that EVs may transform the
      microenvironment of primary tumors thus favoring the selection of cancer cells
      with a metastatic behavior. The release of EVs from resident non-malignant cells
      may contribute to the metastatic processes as well. However, cancer EVs may
      induce malignant transformation in resident mesenchymal stem cells, suggesting
      that the metastatic process is not exclusively due to circulating tumor cells. In
      this review, we outline and discuss evidence-based roles of EVs in actively
      regulating multiple steps of the metastatic process and how we can leverage EVs
      to impair metastasis.

PMID- 29175558
TI  - A complex phenotype in a family with a pathogenic SOX3 missense variant.
AB  - Duplications and deletions of Xq26-27 including SOX3 (Xq27.1) have been
      associated with X-linked mental retardation and isolated growth hormone
      deficiency (OMIM 300123) or X-linked panhypopituitarism (OMIM 312000). Yet,
      pathogenic point mutations seem to be extremely rare. We report a family with
      three affected males with several clinical features including mild intellectual
      disability, microphthalmia, coloboma, hypopituitarism, facial dysmorphology and
      dental anomalies, including microcephaly, retrognathia and a solitary median
      maxillary central incisor amongst other features. Using Whole Exome Sequencing a
      missense variant in SOX3, NM_005634.2:c.449C>A; p.(Ser150Tyr) was identified.
      Segregation analysis in the family demonstrated that the variant was inherited
      through healthy females with its origin in the maternal grandmother showing
      germline mosaicism. Thus, we report one of the first cases of a pathogenic
      variant in SOX3 and germline mosaicism of this variant.

PMID- 29175559
TI  - Desmosterolosis presenting with multiple congenital anomalies.
AB  - Desmosterolosis is a rare multiple congenital anomaly syndrome caused by a defect
      in the enzyme 3-beta-hydroxysterol delta-24-reductase (DHCR24) in the cholesterol
      biosynthesis pathway. Defects in this enzyme cause increased level of the
      cholesterol precursor desmosterol while disrupting development of cholesterol,
      impacting embryogenesis. A total of 9 cases of desmosterolosis have been reported
      to date. We report a 20-month-old male from consanguineous parents with multiple
      congenital anomalies including corpus callosum hypoplasia, facial dysmorphism,
      cleft palate, pectus deformity, short and wide neck and distal contractures. On
      analysis of the regions of homozygosity found by microarray, we identified DHCR24
      as a candidate gene. Sterol quantitation showed a desmosterol level of 162 MUg/mL
      (nl: 0.82 +/- 0.48). Genetic testing confirmed the diagnosis with a homozygous
      likely pathogenic mutation (p.Glu191Lys) in the DHCR24 gene. Our case expands the
      known diagnostic spectrum for Desmosterolosis. We suggest considering
      Desmosterolosis in the differential diagnosis of patients who present with
      concurrent agenesis of the corpus callosum with white matter atrophy and
      ventriculomegaly, retromicrognathia with or without cleft palate, hand
      contractures, and delay of growth and development. Children of consanguineous
      mattings may be at higher risk for rare recessive disorders and testing for
      cholesterol synthesis defect should be a consideration for affected children.
      Initial evaluation can be performed using sterol quantitation, followed by
      genetic testing.

PMID- 29175560
TI  - Protocol and pilot testing: The feasibility and acceptability of a nurse-led
      telephone-based palliative care intervention for patients newly diagnosed with
      lung cancer.

PMID- 29175561
TI  - Corrigendum to "Single-molecule in vivo imaging of bacterial respiratory
      complexes indicates delocalized oxidative phosphorylation" [Biochim. Biophys.
      Acta 1837(6) (2014) 811-824 DOI: 10.1016/j.bbabio.2014.01.020].

PMID- 29175562
TI  - Utilisation and polypharmacy aspects of antiepileptic drugs in elderly versus
      younger patients with epilepsy: A pharmacoepidemiological study of CNS-active
      drugs in Norway, 2004-2015.
AB  - BACKGROUND AND PURPOSE: Many patients with epilepsy use antiepileptic drugs
      (AEDs) in combination. The elderly is a vulnerable group regarding polypharmacy.
      The purpose of this study was to investigate changes in utilisation of AEDs, and
      the extent of polypharmacy with other CNS-active drugs in elderly versus younger
      patients in Norway. METHODS: This pharmacoepidemiological study included all
      prescriptions of antiepileptic, antidepressant and antipsychotic drugs from
      Norwegian pharmacies in the Norwegian Prescription Database (NorPD) (2004-2015).
      Variables included number of patients, utilisation in defined daily doses, age,
      gender, and diagnosis specific reimbursement codes for AEDs. RESULTS: The use of
      AEDs has increased in all age groups in this population-based study in Norway. In
      the elderly, AEDs used in neuropathic pain (mainly gabapentin and pregabalin)
      have increased more than 10-fold (from 0.7 to 9.6 DDDs/1000 elderly/day, 2004
      2015), while the prevalence of users is four times more than in younger patients.
      Polypharmacy between antiepileptic, antidepressant and antipsychotic drugs
      occurred in 35% of elderly and 38% of younger patients with epilepsy. The use of
      enzyme-inducers was common, and occurred more often in elderly patients. A total
      of 42 different interactions that may have clinical implications were identified
      among these drugs. CONCLUSION: The use of AEDs in elderly compared to younger
      patients is increasing, especially in neuropathic pain. Polypharmacy with
      antiepileptic, antidepressant and/or antipsychotic drugs was documented in more
      than one third of the patients. Awareness of increased drug utilisation,
      polypharmacy with potential drug interactions, and focus on elderly patients are
      important for increased patient safety.

PMID- 29175563
TI  - Do neurologists around the world agree when diagnosing epilepsy? - Results of an
      international EpiNet study.
AB  - OBJECTIVE: Previous studies have shown moderate agreement between physicians when
      diagnosing epilepsy, but have included small numbers. The EpiNet study group was
      established to undertake multicentre clinical trials in epilepsy. Before
      commencing trials, we wanted to determine levels of agreement between physicians
      from different countries and different health systems when diagnosing epilepsy,
      specific seizure types and etiologies. METHODS: 30 Case scenarios describing six
      children and 24 adults with paroxysmal events (21 epileptic seizures, nine non
      epileptic attacks) were presented to physicians with an interest in epilepsy.
      Physicians were asked how likely was a diagnosis of epilepsy; if seizures were
      generalised or focal; and the likely etiology. For 23 cases, clinical information
      was presented in Step 1, and investigations in Step 2. RESULTS: 189 Participants
      from 36 countries completed the 30 cases. Levels of agreement were determined for
      154 participants who provided details regarding their clinical experience. There
      was substantial agreement for diagnosis of epilepsy (kappa=0.61); agreement was
      fair to moderate for seizure type(s) (kappa=0.40) and etiology (kappa=0.41). For
      23 cases with two steps, agreement increased from step 1 to step 2 for diagnosis
      of epilepsy (kappa 0.56-0.70), seizure type(s) (kappa 0.38-0.52), and etiology
      (kappa 0.38-0.47). Agreement was better for 53 epileptologists (diagnosis of
      epilepsy, kappa=0.66) than 56 neurologists with a special interest in epilepsy
      (kappa=0.58). Levels of agreement differed slightly between physicians practicing
      in different parts of the world, between child and adult neurologists, and
      according to one's experience with epilepsy. CONCLUSION: Although there is
      substantial agreement when epileptologists diagnose epilepsy, there is less
      agreement for diagnoses of seizure types and etiology. Further education of
      physicians regarding semiology of different seizure types is required.
      Differences in approach to diagnosis, both between physicians and between
      countries, could impact negatively on clinical trials of anti-epileptic drugs.

PMID- 29175564
TI  - Shear horizontal wave propagation in a periodic stubbed plate and its application
      in rainbow trapping.
AB  - The high-order waveguide modal theory, usually used in electromagnetics and
      acoustics, is adopted to investigate the propagation properties of shear
      horizontal waves in a periodic stubbed plate. Beyond the sub-wavelength regime,
      higher-order modes are included to calculate the exact band structures caused by
      the stubs. Theoretical solutions are obtained in a closed form, in which both the
      dynamic governing equations and the boundary conditions are strictly satisfied.
      It is shown that the proposed modelling approach exhibits good convergence and
      accuracy, in agreement with results obtained from the finite element method.
      After a systematic investigation on the influence of the stub on the evolution of
      the band structures, the so-called rainbow trapping phenomenon of SH waves is
      revealed and explored in a graded stubbed plate with monotonously increasing
      height or width of the stubs, featuring an obvious reduction of the group
      velocity and blocking of the wave propagation at different locations for SH waves
      of different frequencies. The proposed model is expected to provide a useful
      theoretical tool for the physical mechanism exploration, structural design and
      eventually system optimization to guide various engineering applications of SH
      waves.

PMID- 29175565
TI  - 3D ultrasound imaging in frequency domain based on concepts of array beam and
      synthetic aperture.
AB  - The high frame rate (HFR) imaging method has the ability to achieve a high frame
      rate. In this method, only one transmission is required to construct a frame of
      image. In our previous work, using a moved one-dimensional (1D) array transducer,
      a three-dimensional (3D) ultrasound imaging method in frequency domain was
      developed. This imaging method was designed based on the concepts of array beam
      and synthetic aperture, which can simplify the two-dimensional (2D) array
      transducer. In this paper, based on array beam and synthetic aperture, the HFR
      imaging method is demonstrated from a novel view. From this view, the
      relationship between the HFR imaging method and synthetic aperture is established
      with the weighting function of array beam. Besides, the HFR imaging method, the
      imaging method with a moved 1D array transducer, and the synthetic aperture
      imaging method with a moved single element transducer are unified in the same
      analytical method with different weighting functions. The same frequency domain
      signal processing flow can be applied to these imaging methods. Comparisons to
      these imaging methods are implemented with simulations. Simulation results show
      that, in the imaging depth of 45 mm, the resolutions calculated as the total
      width of the -6 dB main lobe in x-direction are 1.099 mm, 1.056 mm and 0.596 mm
      for the methods with 1D transducer, 2D transducer and the single element
      transducer, respectively. The resolution in y-direction is 1.054 mm for the
      methods with 2D transducer, and 0.565 mm, 0.593 mm for the 1D and single element
      transducers, respectively. The resolutions in z-direction are 0.493 mm, 0.451 mm
      and 0.452 mm for the 2D, 1D and single element transducers, respectively. The
      resolution in the moved-direction is improved with a moved transducer, but the
      contrast of the image is decreased.

PMID- 29175566
TI  - Quality Enhancement of Ultrasonic TOFD Signals from Carbon Steel Weld Pad with
      Notches.
AB  - Welding is an integral part of component fabrication in industry. Even though the
      science and art of welding are more than 100 years old, defects continue to occur
      during welding. Codes of practice require that the welds be tested and evaluated.
      Conventionally ultrasonic testing has been widely applied in industry for the
      detection and evaluation of the flaws/defects in the weldments. With advances in
      sensor and signal analysis technologies, the last two decades have seen extensive
      developments in the field of ultrasonic testing. We have advanced techniques such
      as Time of Flight Diffraction (TOFD) which has better probability of detection
      for linear defects. A major irritant during the application of TOFD, especially
      for the testing of carbon steel weldments, is the presence of noise. A variety of
      approaches has been used internationally for the suppression of such noise and
      each has its own merits and demerits. This paper focuses on a method of enhancing
      the TOFD A-scan signals in carbon steel weldments by suppressing the noise from
      them using the discrete wavelet transform (DWT). The analysis clearly indicates
      that the DWT gives better signal-to-noise ratio improvement using higher-order
      wavelet filters with 4-level DWT decomposition. However the computational cost of
      this signal enhancement depends on the wavelet filter chosen along with the
      chosen level of DWT decomposition.

PMID- 29175567
TI  - Flat-Detector Computed Tomography for Evaluation of Intracerebral Vasculature for
      Planning of Stereoelectroencephalography Electrode Implantation.
AB  - OBJECTIVE: Stereoelectroencephalography (sEEG) requires extensive preoperative
      planning to optimize placement of electrodes and limit the potential for
      complications. Flat-detector computed tomography (FD-CT) has previously been used
      for perioperative vascular imaging to guide the treatment of vascular lesions.
      This imaging modality provides a detailed depiction of cerebrovascular and bony
      cranial anatomy, which can be used to guide intracranial electrode implantation.
      We have developed a novel method to improve preoperative planning for sEEG
      electrode implantation and limit the potential for postoperative complications by
      using FD-CT imaging merged with preoperative magnetic resonance imaging (MRI).
      METHODS: All patients underwent preoperative FD-CT with selective intra-arterial
      iodinated contrast dye injection through the late arterial and capillary phases
      for evaluation of cerebrovascular anatomy. These results were merged with thin
      cut MRI for trajectory planning of intracranial sEEG electrodes. All patients
      underwent routine CT and MRI after electrode placement. RESULTS: 39 patients have
      undergone sEEG implantation according to this protocol, with a total of 541
      electrodes placed. Additionally, 25 (64.1%) patients underwent implantation of 70
      oblique insular electrodes. There were no clinically significant complications
      after the implantations. Thirty-six (92.3%) patients underwent operative
      intervention, including surgical resection in 27 (69.2%) patients. CONCLUSION: FD
      CT imaging allows for a detailed depiction of cortical cerebrovascular anatomy
      through the capillary phase, in addition to bony cranial anatomy. This enables
      the safe planning of complex trajectories, including high-obliquity insular
      electrodes and transsulcal trajectories through "empty sulci" while also
      providing concurrent imaging of bony anatomy to allow for preoperative planning
      of drill depth and anchor placement.

PMID- 29175568
TI  - Borderline Alberta Stroke Programme Early CT Score Patients with Acute Ischemic
      Stroke Due to Large Vessel Occlusion May Find Benefit with Endovascular
      Thrombectomy.
AB  - OBJECTIVE: Selection of patients with acute ischemic stroke for endovascular
      thrombectomy (EVT) is complex and time-critical. Benefits of EVT are well
      established for patients with small core infarcts. The aim of this study was to
      compare clinical outcomes of EVT in patients with larger established infarcts
      (Alberta Stroke Programme Early CT Score [ASPECTS] <=6) with patients with
      smaller infarcts (ASPECTS 7-10). METHODS: The study included 355 patients with
      acute ischemic stroke due to large vessel occlusion who underwent EVT. ASPECTS
      was assigned to baseline noncontrast computed tomography, and collateral
      perfusion scores were assigned to multiphase computed tomography angiography.
      Baseline stroke severity, collateral grading, and clinical outcome data
      (complication rate, symptomatic intracranial hemorrhage and 90-day modified
      Rankin Scale score) were compared between patients with borderline (<=6) and high
      (7-10) ASPECTS. RESULTS: There were 34 (10%) patients with borderline ASPECTS.
      There was no difference in rate of good clinical outcome (37% vs. 46%, P =
      0.852), symptomatic intracerebral hemorrhage (9% vs. 9%, P = 0.984), or mortality
      (20% vs. 22%, P = 0.818) between patients with borderline ASPECTS and high
      ASPECTS at 90 days. Moreover, there was no significant difference in collateral
      perfusion grade. CONCLUSIONS: This study identifies similar clinical benefit of
      EVT in patients with acute large vessel occlusion stroke with borderline ASPECTS
      and high ASPECTS.

PMID- 29175569
TI  - A Randomized Controlled Trial of Low-Dose Tranexamic Acid versus Placebo to
      Reduce Red Blood Cell Transfusion During Complex Multilevel Spine Fusion Surgery.
AB  - BACKGROUND: Multilevel spine fusion surgery for adult deformity correction is
      associated with significant blood loss and coagulopathy. Tranexamic acid reduces
      blood loss in high-risk surgery, but the efficacy of a low-dose regimen is
      unknown. METHODS: Sixty-one patients undergoing multilevel complex spinal fusion
      with and without osteotomies were randomly assigned to receive low-dose
      tranexamic acid (10 mg/kg loading dose, then 1 mg.kg-1.hr-1 throughout surgery)
      or placebo. The primary outcome was the total volume of red blood cells
      transfused intraoperatively. RESULTS: Thirty-one patients received tranexamic
      acid, and 30 patients received placebo. Patient demographics, risk of major
      transfusion, preoperative hemoglobin, and surgical risk of the 2 groups were
      similar. There was a significant decrease in total volume of red blood cells
      transfused (placebo group median 1460 mL vs. tranexamic acid group 1140 mL;
      median difference 463 mL, 95% confidence interval 15 to 914 mL, P = 0.034), with
      a decrease in cell saver transfusion (placebo group median 490 mL vs. tranexamic
      acid group 256 mL; median difference 166 mL, 95% confidence interval 0 to 368 mL,
      P = 0.042). The decrease in packed red blood cell transfusion did not reach
      statistical significance (placebo group median 1050 mL vs. tranexamic acid group
      600 mL; median difference 300 mL, 95% confidence interval 0 to 600 mL, P =
      0.097). CONCLUSIONS: Our results support the use of low-dose tranexamic acid
      during complex multilevel spine fusion surgery to decrease total red blood cell
      transfusion.

PMID- 29175570
TI  - Reliability of Tokuhashi Score to Predict Prognosis: Comparison of 117 Patients.
AB  - BACKGROUND: Spinal metastatic disease compromises the quality of life and
      prognosis of the patients. Prognosis is an important factor for the decision
      making process and needs to be precise in order to adjust the intensity of
      therapy. The Tokuhashi score is a universal instrument to determine the
      prognosis. The objective was to analyze the effectiveness of the Tokuhashi score
      in determining the prognosis of the patients with spine metastasis by comparing
      the expected survival time from the Tokuhashi score with the survival time
      observed among surgical patients. METHODS: This retrospective study was performed
      from October 2008 to October 2015. The inclusion criteria were symptomatic
      patients with spinal metastasis who underwent spinal cord decompression and had a
      minimum of 1-year follow-up. The exclusion criteria were patients without
      histologic confirmation and were lost to follow-up. The Tokuhashi score was
      applied, and once the expected survival was defined, it was compared with the
      survival time observed in the follow-up. RESULTS: The sample studied was 117
      patients. The commonly female (58%) and breast spinal metastasis was often
      observed (25.6%). The patients were followed for a minimum period of 12 months.
      The actual survival was beyond that estimated by the Tokuhashi score (P < 0.05).
      CONCLUSION: The Tokuhashi score was not reliable to predict the prognosis.
      Patients with lower scores that surgical treatment was not recommended by the
      Tokuhashi score had better quality of life and longer survival after surgery.
      Tokuhashi score is not a precise tool to establish the best therapy and survival
      in patients with spinal metastasis.

PMID- 29175571
TI  - Hypoglossal Schwannoma of Neck: Case Report and Review of Literature.
AB  - BACKGROUND: Schwannomas are benign, slow-growing neoplasms of the myelin
      producing Schwann cells of peripheral nervous system that most commonly affect
      sensory nerves. Hypoglossal schwannomas, tumors of purely motor nerves, comprise
      <5% of all head and neck schwannomas. Since the first description of a
      hypoglossal schwannoma in 1933, there have been few case reports of extracranial
      origins. The most common location of an extracranial hypoglossal schwannoma is in
      the parapharyngeal space and can mimic paragangliomas. We describe the case of a
      woman presenting with an enlarging neck mass originally thought to be a
      paraganglioma but ultimately discovered to be a hypoglossal schwannoma at
      surgery. CASE DESCRIPTION: A 63-year-old woman had a well-circumscribed, mobile,
      nontender, 3-cm firm mass at the mandibular angle. On computed tomography, the
      mass was at the level of the carotid bifurcation, splaying the branching vessels.
      It was further evaluated with magnetic resonance imaging, which revealed a
      homogeneous, T2-hyperintense, T1-isointense mass with homogeneous contrast
      enhancement and scant flow voids. Biopsy revealed a spindle cell mass with
      positive S-100 staining. She underwent resection with the mass originating from
      the hypoglossal nerve. CONCLUSIONS: Hypoglossal schwannomas are rare lesions with
      a variable location along the course of the nerve. An extracranial lesion was
      described here, which was initially mistaken for a paraganglioma. Surgical
      resection is the consensus recommendation and is often well tolerated with low
      risk of long-term recurrence.

PMID- 29175572
TI  - Gamma Knife Surgery for Recurrent Trigeminal Neuralgia in Cases with Previous
      Microvascular Decompression.
AB  - BACKGROUND: Microvascular decompression (MVD) and Gamma Knife surgery (GKS) are
      the primary treatments for trigeminal neuralgia (TN). However, many patients
      require further surgical treatment after initial surgery for recurrent TN. The
      aim of this study was to evaluate efficacy and safety of GKS for recurrent TN
      cases with prior MVD. METHODS: From October 2008 to June 2015, 658 patients at
      West China Hospital underwent GKS as the only surgical treatment, and 42 patients
      underwent GKS with prior MVD. The single 4-mm isocenter was located at the
      cisternal portion of the trigeminal nerve in all patients. Median maximum
      prescription dose was 85 Gy (range, 70-90 Gy). RESULTS: Median follow-up time was
      6.2 years (range, 1.1-10 years). The percentage of patients with or without
      previous MVD within 1 year was 56.81%, and the percentage of patients who were
      pain-free was 74.74%. The recurrence rates within 10 years were 49.11% and 43.74%
      for patients with and without MVD, respectively. Also, 9.52% and 11.04% of
      patients with and without previous MVD experienced complications as a result of
      GKS during the long-term follow-up period. Patients who underwent previous MVD
      showed a significantly lower pain-free rate compared with patients without
      previous MVD (P = 0.01). There was no statistical significance in the recurrence
      rate (P = 0.82) or the complications (P = 0.93) in the 2 groups during the long
      term follow-up period. CONCLUSIONS: For patients with recurrent TN who previously
      underwent MVD, GKS remains an efficacious and safe mode of treatment.

PMID- 29175573
TI  - Cost-Effectiveness of Postoperative Ketamine in Chiari Decompression.
AB  - INTRODUCTION: In Chiari I patients, postoperative pain and discomfort frequently
      slow the transition back to the home setting. OBJECTIVE: We sought to determine
      the effect of standardized ketamine infusion protocols on hospital length of stay
      (LOS). METHODS: This retrospective cohort study reviewed 100 consecutive adult
      patients undergoing Chiari I decompression. Fifty-nine patients were placed on a
      2-3 mg/hr ketamine drip until postoperative day 1. This group was compared with a
      group who received 2-3 mg/hr of ketamine until postoperative day 2 (19 patients)
      and patients who did not receive ketamine at all (22 patients). Clinical
      characteristics, opioid use, LOS, and relative hospitalization costs were
      assessed. All narcotic amounts were converted into milligram equivalents of
      morphine. RESULTS: LOS of the short-ketamine group was 46.5 hours when compared
      with the long-ketamine group (66.8 hours) and no-ketamine group (56.9 hours).
      There was a statistically significant difference when comparing the short
      ketamine group with the long-ketamine group and no-ketamine group together (P <
      0.001), as well as when compared individually (P = 0.001 and 0.004). The mean
      cost of hospitalization was 20% less when a short-ketamine protocol was used (P <
      0.001). Mean morphine milligram equivalents used postoperatively were 148 mg in
      the short-ketamine group, 196 mg in the long-ketamine group, and 187 mg in the no
      ketamine group (P = 0.65). No adverse events from ketamine were noted.
      CONCLUSIONS: Ketamine at subanesthetic levels may be an effective tool to
      facilitate early return home postoperatively and may significantly reduce medical
      costs.

PMID- 29175574
TI  - Surgical Management and Long-Term Seizure Outcome After Surgery for Temporal Lobe
      Epilepsy Associated with Cerebral Cavernous Malformations.
AB  - OBJECTIVE: Operative strategies for cerebral cavernous malformation (CCM)
      associated temporal lobe epilepsy and timing of surgical intervention continue to
      be debated. This study aimed to establish an algorithm to evaluate the efficacy
      of surgical intervention strategies, to maximize positive surgical outcomes and
      minimize postsurgical neurologic deficits. METHODS: 47 patients having undergone
      operation for CCM-associated temporal lobe epilepsy were retrospectively
      reviewed. They had received a diagnostic series for seizure localization,
      including long-term video electroencephalography (vEEG), high-resolution magnetic
      resonance imaging (MRI), and positron emission tomography-computed tomography
      (PET-CT). In patients with mesial temporal lobe CCMs, the involved structures
      (amygdala, hippocampus, or parahippocampal gyrus) were resected in addition to
      the lesions. Patients with neocortical epileptogenic CCM underwent extended
      lesionectomy guided by intraoperative electrocorticography; further performance
      of amygdalohippocampectomy depended on the extent of hippocampal
      epileptogenicity. RESULTS: The study cohort contained 28 patients with drug
      resistant epilepsy (DRE), 12 with chronic epilepsy (CE), and 7 with sporadic
      seizure (SS). Normal temporal lobe metabolism was seen in 7/7 patients of the SS
      group. Hypometabolism was found in all patients with chronic disease except for
      those with posterior inferior and middle temporal gyrus cavernous malformations
      (CMs). Of the 31 patients with superficial neocortical CCM, 7 had normal PET
      without hippocampal sclerosis, 14 had ipsilateral temporal lobe hypometabolism
      without hippocampal sclerosis, and 10 had obvious hippocampal sclerosis and
      hypometabolism. Seizure freedom in DRE, CE, and SS was 82.1%, 75%, and 100%,
      respectively. A significant difference was found between lesion laterality and
      postoperative seizure control; the rate was lower in left-sided cases because of
      less aggressive resection. CONCLUSIONS: Our study demonstrates that the data from
      the presurgical evaluation, particularly regarding CM location, responsiveness to
      antiepileptic drugs, and temporal lobe metabolism, are crucial parameters for
      choosing surgical approaches to CCM-associated temporal lobe epilepsy. By this
      operative strategy, patients may receive maximized seizure control and minimized
      postsurgical neurologic sequelae.

PMID- 29175575
TI  - Brain Granuloma: Rare Complication of a Retained Catheter.
AB  - BACKGROUND: Ventriculoperitoneal (VP) shunt is the most frequent treatment for
      hydrocephalus. VP shunt malfunction is a very common problem in neurosurgical
      practice, often requiring shunt revision procedures. In some cases, complete
      removal of a VP shunt may present difficulties, leading the surgeon to leave the
      ventricular catheter in situ. This decision is often made to avoid possible
      adverse events, primarily risk of life-threatening hemorrhage. However, a
      nonfunctioning catheter left in the ventricular system may lead to further
      complications. CASE DESCRIPTION: We report the case of an adult man who presented
      with a tumor-like cystic lesion, with mural and nodular postcontrast enhancement,
      caused by a huge granuloma formed around the tip of a retained ventricular
      catheter. CONCLUSIONS: This occurrence is extremely rare, and this is the first
      reported case in the literature. Preoperative differential diagnosis was
      challenging and included infection, metastasis, dysembryogenetic lesions, and
      rare reversible porencephalic cysts. According to several physiopathogenetic
      theories recently reported in the literature, the granuloma may develop as the
      result of persistent chronic inflammatory reactions between the ventricular
      catheter left in situ and the brain parenchyma. Application of neuroendoscopic
      techniques is improving management of VP shunt revisions, allowing safe removal
      of catheters stuck or lost in the ventricular system. Neuroendoscopy may
      represent an additional option to avoid possible complications related to
      retained ventricular catheters.

PMID- 29175576
TI  - Potential role of the mitochondria as a target for the hepatotoxic effects of (-)
      epigallocatechin-3-gallate in mice.
AB  - Green tea and (-)-epigallocatechin-3-gallate (EGCG) have been studied for their
      obesity-related health effects. Many green tea extract (GTE)-based dietary
      supplements are commercially-available. Although green tea beverage has a long
      history of safe use, a growing number of case-reports have linked GTE-based
      supplements to incidents of hepatotoxicity. Animal studies support the
      hepatotoxic potential of GTE and EGCG, but the mechanisms remain unclear. Here,
      we examined the hepatotoxic effects of EGCG in C57BL/6J mice and evaluated
      changes in hepatic antioxidant response and mitochondria structure and function.
      Intragastric dosing with EGCG (500 - 750 mg/kg) once daily for 3 d caused hepatic
      inflammation, necrosis, and hemorrhage. Hepatotoxicity was associated with
      increased oxidative stress and decreased superoxide dismutase and glutathione
      peroxidase levels. Real-time PCR and transmission electron microscopy showed
      decreased hepatic mitochondria copy number in EGCG-treated mice. The mRNA levels
      of marker genes of respiratory complex I and III, sirtuin 3, forkhead box O3a,
      and peroxisome-EGCG-treated mice. Sirtuin 3 protein levels were also decreased by
      EGCG. Our data indicate the mitochondria may be a target for EGCG, and that
      inhibition of mitochondria function/antioxidant response may be important for the
      hepatotoxicity of bolus EGCG.

PMID- 29175577
TI  - Aflatoxin exposure in Nigerian children with severe acute malnutrition.
AB  - Aflatoxin exposure is an important public health concern in sub-Saharan Africa as
      well as parts of Latin America and Asia. In addition to hepatocellular carcinoma,
      chronic aflatoxin exposure is believed to play a role in childhood growth
      impairment. The most reliable biomarker of chronic aflatoxin exposure is the
      aflatoxin-albumin adduct, as measured by ELISA or isotope dilution mass
      spectrometry (IDMS). In this report, we have used high resolution LC-MS/MS with
      IDMS to quantitate AFB1-lysine in an extremely vulnerable population of Nigerian
      children suffering from severe acute malnutrition. To increase the sensitivity
      and reliability of the analyses, a labelled AFB1-13C615N2-lysine internal
      standard was synthesized. AFB1-lysine concentrations in this population ranged
      between 0.2 and 59.2 pg/mg albumin, with a median value of 2.6 pg/mg albumin.
      AFB1-lysine concentrations were significantly higher in stunted children (median
      = 4.6 pg/mg) compared to non-stunted (1.2 pg/mg), as well as in children with
      severe acute malnutrition (4.3 pg/mg) compared to controls (0.8 pg/mg). The
      median concentrations were also higher in children with kwashiorkor (6.3 pg/mg)
      compared to those suffering from marasmus (0.9 pg/mg). This is the first report
      of the use of high-resolution mass spectrometry to quantitate AFB1-lysine in
      humans.

PMID- 29175581
TI  - Application of SHAPE reveals in vivo RNA folding under normal and growth-stressed
      conditions in the human parasite Entamoeba histolytica.
AB  - Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) is a
      versatile sequence independent method to probe RNA structure in vivo and in
      vitro. It has so far been tried mainly with model organisms. We show that cells
      of Entamoeba histolytica, a protozoan parasite of humans are hyper-sensitive to
      the in vivo SHAPE reagent, NAI, and show rapid loss of viability and RNA
      integrity. We optimized treatment conditions with 5.8S rRNA and Eh_U3 snoRNA to
      obtain NAI-modification while retaining RNA integrity. The modification patterns
      were highly reproducible. The in vivo folding was different from in vitro and
      correlated well with known interactions of 5.8S rRNA with proteins in vivo. The
      Eh_U3 snoRNA also showed many differences in its in vivo versus in vitro folding,
      which correlated with conserved interactions of this RNA with 18S rRNA and 5'
      ETS. Further, Eh_U3 snoRNA obtained from serum-starved cells showed an open 3'
      hinge structure, indicating disruption of 5'-ETS interaction. This could
      contribute to the observed slow processing of pre-rRNA in starved cells. Our work
      shows the applicability of SHAPE to study in vivo RNA folding in a parasite and
      will encourage the use of this reagent for RNA structure analysis in other such
      organisms.

PMID- 29175578
TI  - Exposure to permethrin promotes high fat diet-induced weight gain and insulin
      resistance in male C57BL/6J mice.
AB  - Permethrin is a pyrethroid pesticide that was previously reported to promote fat
      accumulation and insulin resistance in vitro. A recent study in female mice also
      found that permethrin could promote high fat-induced insulin resistance. The
      effects of permethrin on glucose and lipid metabolisms in male mice, however,
      remain unknown. The purpose of this study was to investigate the effects and
      interactions of permethrin exposure (50, 500, and 5000 MUg/kg body weight/day)
      and dietary fat (low fat, 4% w/w; high fat, 20% w/w) on development of obesity
      and insulin resistance in male C57BL/6J mice. Our results showed that permethrin
      treatment significantly increased body weight, fat mass, and insulin resistance
      with high fat diet, but not with low fat diet, without influencing energy intake.
      Permethrin treatment also significantly increased serum levels of insulin,
      glucose, leptin, triglycerides and cholesterol. Further results showed that
      permethrin inhibited AMP-activated protein kinase in white adipose tissue. These
      results suggest that permethrin interacts with dietary fat to alter lipid and
      glucose metabolisms in male C57BL/6J mice.

PMID- 29175580
TI  - RIFM fragrance ingredient safety assessment, l-menthyl lactate, CAS Registry
      Number 59259-38-0.

PMID- 29175579
TI  - RIFM fragrance ingredient safety assessment, dodecanal dimethyl acetal, CAS
      Registry Number 14620-52-1.

PMID- 29175582
TI  - Usefulness of coronary postmortem computed tomography angiography to detect
      lesions in the coronary artery and myocardium in cases of sudden death.
AB  - Coronary postmortem computed tomography angiography (coronary PMCTA) has been
      introduced as a routine examination procedure for autopsy at our department.
      Here, we reviewed eight autopsy cases in which apparent histopathological changes
      including acute myocardial infarction (AMI), anomalous aortic origin of a
      coronary artery (AAOCA), hypertrophic obstructive cardiomyopathy (HOCM) and acute
      myocarditis were involved in the cause of death. For investigation of the
      coronary artery and shape of the heart, coronary PMCTA was valuable in detecting
      narrowing or obstruction of coronary artery in AMI, indicating an anomalous
      aortic origin of the left coronary artery in AAOCA, and demonstrating septal
      hypertrophy and intracavitary obstruction in HOCM. However, it was debatable
      whether the hypervascularity demonstrated by coronary PMCTA in the case of acute
      myocarditis was more prominent than the vascular images obtained in other cases
      without inflammation. Thus, coronary PMCTA appeared to be useful not only for
      detection of coronary artery stenosis, but also for indicating other distinctive
      changes involved in AAOCA and HOCM.

PMID- 29175583
TI  - Assessing the FBI's Native American STR database for random match probability
      calculations.
AB  - In forensic statistics, the random match probability (RMP) is the probability
      that a "match" would occur by coincidence while the likelihood ratio (LR)
      describes the strength of DNA evidence. Using these statistics to assess the
      weight of DNA evidence requires an appropriate and well-characterized population
      specific short tandem repeat (STR) database to reliably estimate allele
      frequencies. This study compared several Native American-specific STR datasets,
      including those not represented in the CODIS Native American database, and
      revealed that increasing the number of STR markers resulted in lower RMP values
      while a theta adjustment from 0.03 to 0.04 generated increases in RMP. To prevent
      biases that may arise from the underrepresentation of tribes in the current CODIS
      Native American database, data derived from tribes in different geographic
      regions and language families are necessary to ensure inclusive representation of
      the Native American population and generate more reliable statistical results.

PMID- 29175584
TI  - Coronary artery tuberculosis: An unusual case of sudden death.

PMID- 29175585
TI  - Unprotected primary sulfonamide group facilitates ring-forming cascade en route
      to polycyclic [1,4]oxazepine-based carbonic anhydrase inhibitors.
AB  - 4-Chloro-3-nitrobenzenesulfonamide reacted cleanly at room-temperature with a
      range of bis-electrophilic phenols bearing an NH-acidic functionality (secondary
      carboxamide or pyrazole) in the ortho-position. This produced a novel class of
      [1,4]oxazepine-based primary sulfonamides which exhibited strong inhibition of
      therapeutically relevant human carbonic anhydrases. 2-Chloronitrobenzene did not
      enter a similar cyclocondensation process, even under prolonged heating. Thus,
      the primary sulfonamide functionality plays a dual role by enabling the
      [1,4]oxazepine ring construction and acting as a enzyme prosthetic zinc-binding
      group when the resulting [1,4]oxazepine sulfonamides are employed as carbonic
      anhydrase inhibitors.

PMID- 29175586
TI  - Design, synthesis of novel Triazolones and bis-Triazolones derivatives under
      ultrasound irradiation and evaluation as potent angiotensin converting enzyme
      (ACE) inhibitors.
AB  - The condensation of several primary amines and diamines with various N1
      ethoxycarbonyles N1-tosylhydrazonates (1a-b), triazolones (2) and bis-triazolone
      (3) resulted in ethanol under ultrasound irradiation. Compared with the
      conventional methods, the main advantages of the present procedure are milder
      conditions, shorter reaction time and higher yields. The newly synthesized
      compounds were evaluated for angiotensin I-converting enzyme (ACE) inhibition.
      The results were compared to Captopril as a reference drug. Compounds 3b, 2h, 3a,
      2d, and 2f showed not only inhibition activity with IC50 values of 0.162, 0.253,
      0.253, 0.281 and 0.382 uM, respectively, but also minimal toxicity. The docking
      of chemical compounds in the ACE active site showed possible inhibitory effect of
      all compounds on the catalytic activity of the enzyme, which would satisfactorily
      explain the anti-hypertensive effect of these compounds.

PMID- 29175587
TI  - Design, synthesis and molecular modeling studies of new series of antitumor 1,2,4
      triazines with potential c-Met kinase inhibitory activity.
AB  - The receptor tyrosine kinase c-Met is an attractive target for therapeutic
      treatment of cancers nowadays. Herein we describe the design and synthesis of a
      novel series of 1,2,4-triazine derivatives based on our lead NCI 748494/1,
      possessing different N-linkers to aromatic and heterocyclic rings. In addition, a
      molecular hybrid series combining the 1,2,4-triazine scaffold to the well-known
      anticancer drug 6-mercaptopurine (6-MP) was synthesized in order to explore its
      "double-drug" antitumor effect. The synthesized compounds were evaluated for
      their in vitro antitumor activity against three c-Met addicted cancer cell lines
      (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antitumor
      activity. Compound 3d showed potent inhibitory activity more than reference
      Foretinib, BMS-777607 and NCI 748494/1 with IC50 values in the range 0.01-0.31 uM
      against the cancer cell lines. The calculated IC50 of 3d against c-Met kinase was
      found to be 2.71 uM, which is more potent than NCI 748494/1 (IC50 = 31.70 uM).
      Docking studies were performed to identify the binding mode of 3d with c-Met
      kinase domain in comparison to moderate and weak derivatives. The present study
      clearly demonstrates that 1,2,4-triazine ring exhibits promising antitumor
      activity and the double-drug optimization strategy led to identifying 3d as a
      potent c-Met kinase inhibitor suitable for further development.

PMID- 29175588
TI  - Modification of Bischler-Mohlau indole derivatives through palladium catalyzed
      Suzuki reaction as effective cholinesterase inhibitors, their kinetic and
      molecular docking studies.
AB  - Due to the immense importance of aryl indole nucleus, herein we report the
      palladium-catalyzed arylation of N-substituted 2-aryl indole utilizing Suzuki
      Miyaura cross coupling methodology. The biological screening for cholinesterase
      inhibition of the resulted biaryl indole moieties was carried out to evaluate
      their pharmacological potential, expecting to involve the development of new
      therapeutics for various inflammatory, cardiovascular, gastrointestinal and
      neurological diseases. This research work also involved the use of utilization of
      microwave-assisted organic synthesis (MAOS) for the synthesis of Bischler-Mohlau
      indole which is further biarylated via palladium-catalyzed cross coupling
      reaction. All the synthetic compounds (3a-n) were tested for cholinesterase
      inhibition and exhibited high level of AChE inhibitory activities. Interestingly,
      compounds 3m and 3n were found to be dual inhibitors, however, remaining compound
      exhibited no inhibitory activity against BChE. The biological potential of the
      resulted compounds was explained on the basis of molecular docking studies,
      performed against AChE and BChE, exploring the probable binding modes of most
      potent inhibitors.

PMID- 29175589
TI  - Design, synthesis, monoamine oxidase inhibition and docking studies of new
      dithiocarbamate derivatives bearing benzylamine moiety.
AB  - A new series of thirteen 2-[(4-fluorophenyl)(4-nitrobenzyl)amino]-2-oxoethyl-1
      substituted-carbodithioate derivatives (4a-4m) were synthesized and tested for
      their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory potential by
      an in vitro fluorometric method. Most of the compounds have found to be selective
      towards MAO-B than MAO-A. Compound 4j that carrying 4-nitrophenyl piperazine
      moiety, was detected as the most active agent amongst all compounds with the IC50
      value of 0.097 +/- 0.003 uM for MAO-B while that of selegiline was 0.040 +/-
      0.002 uM. The enzyme kinetic study reported that compound 4j is a reversible and
      non-competitive inhibitor. Interaction modes between the hMAO-B and compound 4j
      were determined by docking studies. The study also revealed that compound 4j has
      the highest binding scores. Besides, compound 4j has not cytotoxicity at its
      effective concentration against hMAO-B.

PMID- 29175590
TI  - Recovering Wood and McCarthy's ERP-prototypes by means of ERP-specific procrustes
      rotation.
AB  - BACKGROUND: The misallocation of treatment-variance on the wrong component has
      been discussed in the context of temporal principal component analysis of event
      related potentials. There is, until now, no rotation-method that can perfectly
      recover Wood and McCarthy's prototypes without making use of additional
      information on treatment-effects. NEW METHOD: In order to close this gap, two new
      methods: for component rotation were proposed. After Varimax-prerotation, the
      first method identifies very small slopes of successive loadings. The
      corresponding loadings are set to zero in a target-matrix for event-related
      orthogonal partial Procrustes- (EPP-) rotation. The second method generates
      Gaussian normal distributions around the peaks of the Varimax-loadings and
      performs orthogonal Procrustes-rotation towards these Gaussian distributions.
      Oblique versions of this Gaussian event-related Procrustes- (GEP) rotation and of
      EPP-rotation are based on Promax-rotation. RESULTS: A simulation study revealed
      that the new orthogonal rotations recover Wood and McCarthy's prototypes and
      eliminate misallocation of treatment-variance. In an additional simulation study
      with a more pronounced overlap of the prototypes GEP Promax-rotation reduced the
      variance misallocation slightly more than EPP Promax-rotation. Comparison with
      Existing Method(s): Varimax- and conventional Promax-rotations resulted in
      substantial misallocations of variance in simulation studies when components had
      temporal overlap. A substantially reduced misallocation of variance occurred with
      the EPP-, EPP Promax-, GEP-, and GEP Promax-rotations. CONCLUSIONS: Misallocation
      of variance can be minimized by means of the new rotation methods: Making use of
      information on the temporal order of the loadings may allow for improvements of
      the rotation of temporal PCA components.

PMID- 29175591
TI  - Linking T cell epitopes to a common linear B cell epitope: A targeting and
      adjuvant strategy to improve T cell responses.
AB  - Immune complexes are potent mediators of cellular immunity and have been
      extensively studied for their disease mediating properties in humans and for
      their role in anti-cancer immunity. However, a viable approach to use antibody
      complexed antigen as vehicle for specific immunotherapy has not yet reached
      clinical use. Since virtually all people have endogenous antibodies against
      tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates
      to utilize for immune modulation. As an initial proof-of-concept we investigated
      if anti-tetanus IgG could induce potent cross-presentation of a conjugate with
      SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd. This
      protein conjugate enhanced OVA-specific CD8+ T cell responses when administrated
      to seropositive mice. Since TTd is poorly defined, we next investigated whether a
      synthetic peptide-peptide conjugate, with a chemically defined linear B cell
      epitope of tetanus toxin (TTx) origin, could improve cellular immune responses.
      Herein we identify one linear B cell epitope, here after named MTTE thru a
      screening of overlapping peptides from the alpha and beta region of TTx, and by
      assessment of the binding of pooled IgG, or individual human IgG from high-titer
      TTd vaccinated donors, to these peptides. Subsequently, we developed a chemical
      protocol to synthesize defined conjugates containing multiple copies of MTTE
      covalently attached to one or more T cell epitopes of choice. To demonstrate the
      potential of the above approach we showed that immune complexes of anti-MTTE
      antibodies with MTTE-containing conjugates are able to induce DC and T cell
      activation using model antigens.

PMID- 29175592
TI  - Role of extracellular vesicles in rheumatoid arthritis.
AB  - Cell-derived extracellular vesicles (EVs) are involved in the pathogenesis of
      rheumatoid arthritis (RA), playing important roles in antigen presentation,
      inflammation, angiogenesis, cell-cell signal communication, thrombosis, and
      articular cartilage extracellular matrix degradation. Understanding the
      pathogenic mechanism of RA is important for developing therapies. The pathogenic
      indicators of RA, such as submicron-sized EVs, represent promising biomarkers for
      evaluating RA activity. This review summarizes the recent advances in
      understanding the pathogenesis of RA, and sheds light on the pathogenic as well
      as anti-inflammatory or immunosuppressive roles of EVs. We suggest that EVs could
      be harnessed as tools for drug delivery or targets for RA therapies.

PMID- 29175593
TI  - Rational selection of immunodominant and preserved epitope Sm043300e from
      Schistosoma mansoni and design of a chimeric molecule for biotechnological
      purposes.
AB  - Human schistosomiasis is a neglected tropical disease of great importance in
      public health. A large number of people are infected with schistosomiasis, making
      vaccine development and effective diagnosis important control strategies. A
      rational epitope prediction workflow using Schistosoma mansoni hypothetical
      proteins was previously presented by our group, and an improvement to that
      approach is presented here. Briefly, immunodominant epitopes from parasite
      membrane proteins were predicted by reverse vaccinology strategy with additional
      in silico analysis. Furthermore, epitope recognition was evaluated using sera of
      individuals infected with S. mansoni. The epitope that stood out in both in
      silico and in vitro assays was used to compose a rational chimeric molecule to
      improve immune response activation. Out of 2185 transmembrane proteins, four
      epitopes with high binding affinities for human and mouse MHCII molecules were
      selected through computational screening. These epitopes were synthesized to
      evaluate their ability to induce TCD4+ lymphocyte proliferation in mice.
      Sm204830e and Sm043300e induced significant TCD4+ proliferation. Both epitopes
      were submitted to enzyme-linked immunosorbent assay to evaluate their recognition
      by IgG antibodies from the sera of infected individuals, and epitope Sm043300 was
      significantly recognized in most sera samples. Epitope Sm043300 also showed good
      affinity for human MHCII molecules in molecular docking, and its sequence is
      curiously highly conserved in four S. mansoni proteins, all of which are
      described as G-protein-coupled receptors. In addition, we have demonstrated the
      feasibility of incorporating this epitope, which showed low similarity to human
      sequences, into a chimeric molecule. The stability of the molecule was evaluated
      by molecular modeling aimed at future molecule production for use in diagnosis
      and vaccination trials.

PMID- 29175594
TI  - Reduced PTEN involved in primary immune thrombocytopenia via contributing to B
      cell hyper-responsiveness.
AB  - Phosphatase and tensin homolog (PTEN) is thought to mediate B cell activation by
      negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway.
      This pathway is important for activation, growth, and proliferation. Although
      enhanced B cell receptor (BCR) signaling contributes to increased B cell activity
      in immune thrombocytopenia (ITP), the role of PTEN is unclear. In this study, we
      analyzed B cells of ITP patients using flow cytometry and found that all B cell
      subsets, excluding memory B cells, showed lower PTEN expression than cells from
      healthy controls (HCs). PTEN expression was also positively-correlated with blood
      platelet count, although levels were lower in patients who were platelet
      autoantibody-positive compared with those who were negative. We next evaluated
      the effects of IL-21, anti-IgM, and CD40L on PTEN expression, demonstrating that
      they were potent inducers of PTEN expression in normal B cells. Induction of PTEN
      expression was lower in B cells of ITP patients. We also found that IL-21
      increased the proportion of plasma cells in peripheral blood mononuclear cells
      (PBMCs) of ITP patients, independent of BCR signaling. This effect was
      reproducible using PTEN inhibitors with cells from HCs. In summary, defective
      PTEN expression, regulation, and function all contribute to the B cell hyper
      responsiveness that associates with ITP.

PMID- 29175595
TI  - The development of an instructional video for the teaching of acupressure for
      pain management in acute musculoskeletal injuries: A knowledge translation study.
AB  - OBJECTIVES: To survey potential stakeholders to obtain information relevant to
      the production of a video on teaching acupressure for sports injury management,
      and gain feedback from potential users on the prototype video. DESIGN: Focus
      groups and online survey methods nested within a knowledge translation framework.
      PARTICIPANTS: Four focus groups (n = 24) were conducted, two with sports medics
      and two with sports physiotherapists as a part of the development of a prototype
      video. Nineteen stakeholders viewed the prototype video and participated in the
      subsequent online survey. MAIN OUTCOME MEASURES: Focus groups' transcripts were
      analysed to develop themes using a general inductive approach. Survey data
      analysis incorporated quantitative and qualitative analysis. RESULTS: Three key
      themes concerning the design of the video emerged from the focus groups: 1) the
      recommendation for both demonstration and verbal instructions on the acupressure
      technique; 2) keeping the content of the video to a minimum; and 3) the need for
      professionalism in the production of the video, and highlighting the presenter's
      expertise and qualifications. The survey participants found the video to be clear
      and professional. CONCLUSIONS: Collectively these studies described the
      development and assessment of a user-oriented instructional video on teaching of
      acupressure for the management of sports injuries.

PMID- 29175596
TI  - Evaluation of cardiovascular responses to silver nanoparticles (AgNPs) in
      spontaneously hypertensive rats.
AB  - Silver nanoparticles (AgNPs) are used in the medical, pharmaceutical and food
      industry. Adverse effects and toxicity induced by AgNPs upon cardiac function
      related to nitric oxide (NO) and oxidative stress (OS) are described. AgNPs
      toxicity may be influenced by cardiovascular pathologies such as hypertension.
      However, the molecules involved under pathophysiological conditions are not well
      studied. The aim of this work was to evaluate perfusion pressure (PP) and left
      ventricle pressure (LVP) as physiological parameters of cardiovascular function
      in response to AgNPs, using isolated perfused hearts from spontaneously
      hypertensive rats (SHR), and identify the role of NO and OS. The results suggest
      that AgNPs reduced NO derived from endothelial/inducible NO-synthase and
      increased OS, leading to increased and sustained vasoconstriction and myocardial
      contractility. Additionally, the hypertension condition alters phenylephrine
      (Phe) and acetylcholine (ACh) classic effects. These data suggest that
      hypertension intensified AgNPs-cardiotoxicity. Nevertheless, the precise
      mechanism of action is still under elucidation.

PMID- 29175597
TI  - Delivery of NF-kappaB shRNA using carbamate-mannose modified PEI for eliminating
      cancer stem cells.
AB  - The presence of cancer stem cells (CSCs) is one of the main reasons that cause
      cancer relapse and metastasis. In this study, NF-kappaB shRNA was delivered to
      target CSCs using carbamate-mannose modified PEI (CMP) as a non-viral gene
      vector. The polymer was synthesized by blocking primary amine groups of branched
      PEI (10kDa) through nucleophilic addition between PEI and protected mannose
      functionalized cyclic carbonate, followed by mannose deprotection. CMP/control
      shRNA nanocomplexes showed lower cytotoxicity and higher transfection efficiency
      in 4T1 murine breast cancer cells than unmodified PEI/control shRNA
      nanocomplexes. Importantly, CMP/NF-kappaB shRNA nanocomplexes (CMPN) were capable
      of inhibiting migration and invasion, decreasing mammosphere and colony formation
      and lowering ALDH+ CSC population. Furthermore, CMPN not only induced apoptosis
      and inhibited cell proliferation, but also sensitized the cells to the treatment
      with doxorubicin-loaded micellar nanoparticles. Therefore, CMPN may provide a
      promising approach for eliminating CSCs to prevent cancer relapse and metastasis.

PMID- 29175598
TI  - Low immunogenic bio-nanocapsule based on hepatitis B virus escape mutants.
AB  - Bio-nanocapsules (BNCs) consisting of hepatitis B virus surface antigen (HBsAg) L
      proteins and phospholipids are used as efficient non-viral carriers for liver
      specific delivery of genes and drugs. Considering the administration to HB
      vaccinees and HB patients, endogenous anti-HBsAg immunoglobulins (HBIGs) may
      reduce the delivery efficacy and prevent repetitive administration. Therefore,
      low immunogenic BNCs were generated by inserting two point mutations in the HBsAg
      L protein, which were found in HBV escape mutants. Escape mutant-type BNC (emBNC)
      showed 50% lower HBIG binding capacity than that of parental BNC (wtBNC). It
      induced HBIG production to a lesser extent than that associated with wtBNC in
      BALB/c mice. The emBNC could accumulate into human hepatocyte-derived tumor in
      mice pre-treated with HBIGs. The complex of emBNC and cationic liposomes could
      deliver plasmid DNA to HepG2 cells efficiently in the presence of HBIGs. Thus,
      emBNC could evade HBIG-neutralizing antibodies, expanding the clinical utility of
      BNC-based nanomedicine.

PMID- 29175599
TI  - Multimodal imaging for a theranostic approach in a murine model of B-cell
      lymphoma with engineered nanoparticles.
AB  - Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and
      theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active
      groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic
      cells express on their surfaces a clone-specific immunoglobulin receptor (Ig
      BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20
      lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan
      HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the
      tumor burden in a murine xenograft model. We monitored tumor growth using high
      frequency ultrasonography and demonstrated targeting specificity and kinetics of
      the NPs via in vivo fluorescent reflectance imaging. This result was also
      confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In
      conclusion, we demonstrated the ability of NPs loaded with fluorescent and
      paramagnetic tracers to act as multimodal imaging contrast agents and hence as a
      non-toxic, highly specific theranostic system.

PMID- 29175600
TI  - Forensic DNA methylation profiling from minimal traces: How low can we go?
AB  - Analysis of human DNA methylation (DNAm) can provide additional investigative
      leads in crime cases, e.g. the type of tissue or body fluid, the chronological
      age of an individual, and differentiation between identical twins. In contrast to
      the genetic profile, the DNAm level is not the same in every cell. At the single
      cell level, DNAm represents a binary event at a defined CpG site (methylated
      versus non-methylated). The DNAm level from a DNA extract however represents the
      average level of methylation of the CpG of interest of all molecules in the
      forensic sample. The variance of DNAm levels between replicates is often
      attributed to technological issues, i.e. degradation of DNA due to bisulfite
      treatment, preferential amplification of DNA, and amplification failure. On the
      other hand, we show that stochastic variations can lead to gross fluctuation in
      the analysis of methylation levels in samples with low DNA levels. This
      stochasticity in DNAm results is relevant since low DNA amounts (1pg - 1ng) is
      rather the norm than the exception when analyzing forensic DNA samples. This
      study describes a conceptual analysis of DNAm profiling and its dependence on the
      amount of input DNA. We took a close look at the variation of DNAm analysis due
      to DNA input and its consequences for different DNAm-based forensic applications.
      As can be expected, the 95%-confidence interval of measured DNAm becomes narrower
      with increasing amounts of DNA. We compared this aspect for two different DNAm
      based forensic applications: body fluid identification and chronological age
      determination. Our study shows that DNA amount should be well considered when
      using DNAm for forensic applications.

PMID- 29175601
TI  - Sciatica due to hydroxyapatite deposition disease.

PMID- 29175602
TI  - Synthesis, molecular docking, antimicrobial, antioxidant and toxicity assessment
      of quinoline peptides.
AB  - A series of quinoline based peptides were synthesized by a one-pot reaction
      through Ugi-four component condensation of lipoic acid, cyclohexyl isocyanide,
      aniline derivatives and 2-methoxy quinoline-3-carbaldehyde derivatives under
      microwave irradiation. The products were obtained in excellent yields and high
      purity. Solvent optimization and the effect of microwave irradiation with various
      powers were also observed. All the synthesized compounds were characterized by
      FTIR, NMR spectral data and elemental analysis. A total of eight peptides were
      subjected to antimicrobial, antioxidant and toxicity evaluation. Among them, four
      peptides showed potential towards antibacterial screening with Bacillus cereus,
      Staphylococcus aureus, Escherichia coli, Enterococcus faecalis and Candida
      albicans, Candida utilis and three peptides showed antioxidant test positive
      (DPPH). Besides, toxicity of all the peptides were evaluated by using brine
      shrimp and it was observed that four peptides showed mortality rate less than 50%
      up to 48h. Molecular docking studies revealed that the higher binding affinity of
      the two peptides toward DNA gyrase than ciprofloxacin based on Libdock score. The
      described chemistry represents a facile tool to synthesize complex heterocycles
      of pharmaceutical relevance in a highly efficient and one-pot fashion. The
      advantages of this method are its green approach, inexpensive solvent, shorter
      reaction times and excellent yields.

PMID- 29175603
TI  - Monitoring of hydrogen peroxide production under photodynamic treatment using
      protein sensor HyPer.
AB  - An interest to H2O2 accumulation under photodynamic treatment can be explained by
      its participation in intracellular signal cascades. It is important not only to
      detect H2O2 generation, but also to trace the dynamics of its intracellular
      content. In the present study the dynamics of cellular H2O2 content under
      photodynamic treatment was analyzed using genetically encoded reversible H2O2
      sensitive sensor HyPer. Real-time detecting of H2O2 production after photodynamic
      treatment was performed using the protein sensor and individual features of
      action of different photosensitizers were revealed. Photodynamic treatment with a
      number of chlorin and phthalocyanine photosensitizers was found to induce
      secondary production of H2O2 in the cells. Three types of dynamic responses were
      registered: monotonous increase of H2O2 level during the entire observation time
      in the presence of Fotoditazin and Holosens; transient short-term accumulation in
      the presence of Radachlorin and Phthalosens; and relatively low-level stable
      increase in the presence of Photosens. The listed photosensitizers differ
      significantly in intracellular localization and physicochemical properties, which
      can determine the differences in the response of H2O2 after the photodynamic
      treatment. In general, it has been shown that the rapid transient H2O2 response
      is typical for hydrophobic compounds localized in membrane cell structures,
      whereas in the presence of more hydrophilic dyes a prolonged monotonous H2O2
      accumulation occurs.

PMID- 29175604
TI  - Harnessing the wine dregs: An approach towards a more sustainable synthesis of
      gold and silver nanoparticles.
AB  - In recent years, the management of food waste processing has emerged as a major
      concern. One such type of food waste, grape pomace, has been shown to be a great
      source of bioactive compounds which might be used for more environmentally -
      friendly processes for the synthesis of nanomaterials. In this study, grape
      pomace of Vitis vinifera has been used for the obtainment of an aqueous extract.
      Firstly, the reducing activity, total phenolic content and DPPH scavenging
      activity of the aqueous extract were determined. Then, the aqueous extract was
      used for the synthesis of gold and silver nanoparticles. The formation of
      spherical and stable nanoparticles with mean diameters of 35.3+/-5.2nm for Au@GP
      and 42.9+/-6.4nm for Ag@GP was confirmed by UV-vis spectroscopy and transmission
      electron microscopy. Furthermore, the functional group of biomolecules present in
      grape pomace extract, Au@GP and Ag@GP, were characterized by Fourier transform
      infrared spectroscopy prior to and after the synthesis, in order to obtain
      information about the biomolecules involved in the reducing and stabilization
      process. This study is the first to deal with the use of Vitis vinifera grape
      pomace in obtaining gold and silver nanoparticles through an eco-friendly, quick,
      one-pot synthetic route.

PMID- 29175605
TI  - Elevated CO2 leads to carbon sequestration by modulating C4 photosynthesis
      pathway enzyme (PPDK) in Suaeda monoica and S. fruticosa.
AB  - The C4 halophytic species Suaeda monoica and S. fruticosa, possess the C4
      photosynthesis pathway without Kranz anatomy were grown at ambient (470ppm CO2)
      and elevated (850ppm CO2) atmospheric CO2 under control containment facility to
      study the plant response under CO2 stress condition. The relative growth of both
      Suaeda species was enhanced with atmospheric CO2 enrichment compared to control
      (ambient) condition. The photosynthesis rate was found 2.5MUmolCO2m-2s-1 in both
      species under stress condition compared to about 1.9MUmolCO2m-2s-1 under control
      conditions. About 0.3molH2Om-2s-1 conductance was detected under an unstressed
      condition which decreased significantly to ~0.07molH2Om-2s-1 on the 6th day of
      stress treatment. Similarly, transpiration rate was also decreased significantly
      from 4.4-5.2mmolH2Om-2s-1 to 1.7-1.9 under stress condition. In contrast, VpdL
      increased significantly from 1.9kPa to 2.5kPa under stress condition. A higher
      total chlorophyll content observed in S. monoica (56.36mgg-1 tissue) compared to
      S. fruticosa (33.12mgg-1 tissue) under unstressed (control) condition. A
      significant increase was found in the total chlorophyll content of S. fruticosa
      (45.47mgg-1 tissue) with stress treatment compared to control (33.12mgg-1
      tissue). In contrast, the total chlorophyll decreased in S. monoica (51.58mgg-1
      tissue) under similar stress condition compared to control plants (56.36mgg-1
      tissue). About 6-6.8mg total sugar per gram tissue found under control condition
      which enhanced further (7.5 to 11mgg-1 tissue) under stress condition. Similarly,
      total reducing sugar (~2mgg-1 tissue) and total starch content (6.5-11mgg-1
      tissue) increased under stress condition. About 6.5- and 3- fold higher
      expression of PPDK gene was observed for S. monoica and S. fruticosa,
      respectively under CO2 stress condition. PPDK (1.2- and 1.5- fold) and
      antioxidant enzymes; APX (12.7- and two-fold), CAT (2.2- and 6.4- fold) and SOD
      (4.6- and 94- fold) enhanced significantly in S. fruticosa and S. monoica,
      respectively under high CO2 stress condition compared to control plants. Overall,
      it was observed that PPDK enzyme plays a key role in C4 photosynthesis pathway
      and S. monoica is a potential candidate to be explored further for the saline
      agricultural and CO2 capture.

PMID- 29175606
TI  - High rates of colonisation by ampicillin-resistant enterococci in residents of
      long-term care facilities in Porto, Portugal.
AB  - This study evaluated the occurrence of enterococci resistant to clinically
      relevant antibiotics in long-term care facility (LTCF) residents in Porto,
      Portugal, a region with high rates of multidrug-resistant enterococci in infected
      patients and healthy carriers. Faecal samples from 48 residents in two LTCFs
      (2015-2016) were enriched (with/without antibiotics) and plated on Slanetz
      Bartley with/without the same antibiotics (ampicillin/vancomycin/linezolid). Two
      colonies per morphology/sample were selected for susceptibility testing and
      species identification. Clonality was established by PFGE and MLST. Genes coding
      for vancomycin resistance (vanA/vanB), virulence and plasmids (replicases) were
      searched by PCR. A total of 285 isolates were obtained, comprising Enterococcus
      faecalis, Enterococcus faecium, Enterococcus raffinosus and Enterococcus avium
      colonising 83%, 77%, 27% and 10% of residents, respectively. Residents from both
      LTCFs were colonised with vancomycin-resistant E. faecium (VanA-VREfm) (4
      residents; 8%) and/or ampicillin-resistant (AmpR) (24 residents; 50%) E.
      raffinosus, E. faecium and E. avium. Enterococcus faecium previously associated
      with major human clonal lineages (ST18/ST78) or animal clones (ST393) were
      identified. Some PFGE types of E. faecium, E. raffinosus and E. avium were shared
      by residents of both LTCFs. Recent antibiotic exposure was significantly
      associated with colonisation by AmpR enterococci. Residents from Portuguese LTCFs
      were colonised with high rates of AmpR enterococci and similar rates of VREfm
      compared with other EU countries. A high colonisation rate with widespread
      enterococcal lineages that could be selected by antibiotic consumption in LTCFs
      was uncovered. These findings suggest that antimicrobial stewardship is warranted
      in LTCFs, which constitutes a significant challenge in a home-based setting.

PMID- 29175607
TI  - Stability of two-species communities: Drift, environmental stochasticity, storage
      effect and selection.
AB  - The dynamics of two competing species in a finite size community is one of the
      most studied problems in population genetics and community ecology. Stochastic
      fluctuations lead, inevitably, to the extinction of one of the species, but the
      relevant timescale depends on the underlying dynamics. The persistence time of
      the community has been calculated both for neutral models, where the only driving
      force of the system is drift (demographic stochasticity), and for models with
      strong selection. Following recent analyses that stress the importance of
      environmental stochasticity in empirical systems, we present here a general
      theory of the persistence time of a two-species community where drift,
      environmental variations and time independent selective advantage are all taken
      into account.

PMID- 29175608
TI  - Temporal ordering of substitutions in RNA evolution: Uncovering the structural
      evolution of the Human Accelerated Region 1.
AB  - The Human Accelerated Region 1 (HAR1) is the most rapidly evolving region in the
      human genome. It is part of two overlapping long non-coding RNAs, has a length of
      only 118 nucleotides and features 18 human specific changes compared to an
      ancestral sequence that is extremely well conserved across non-human primates.
      The human HAR1 forms a stable secondary structure that is strikingly different
      from the one in chimpanzee as well as other closely related species, again
      emphasizing its human-specific evolutionary history. This suggests that positive
      selection has acted to stabilize human-specific features in the ensemble of HAR1
      secondary structures. To investigate the evolutionary history of the human HAR1
      structure, we developed a computational model that evaluates the relative
      likelihood of evolutionary trajectories as a probabilistic version of a
      Hamiltonian path problem. The model predicts that the most likely last step in
      turning the ancestral primate HAR1 into the human HAR1 was exactly the
      substitution that distinguishes the modern human HAR1 sequence from that of
      Denisovan, an archaic human, providing independent support for our model. The
      MutationOrder software is available for download and can be applied to other
      instances of RNA structure evolution.

PMID- 29175609
TI  - Corrigendum to "Inconsistency in 9mm bullets: Correlation of jacket thickness to
      post-impact geometry measured with non-destructive X-ray computed tomography"
      [Forensic Sci. Int. 234C (2014) 111-119].

PMID- 29175610
TI  - Large-scale coupling dynamics of instructed reversal learning.
AB  - The ability to rapidly learn from others by instruction is an important
      characteristic of human cognition. A recent study found that the rapid transfer
      from initial instructions to fluid behavior is supported by changes of functional
      connectivity between and within several large-scale brain networks, and
      particularly by the coupling of the dorsal attention network (DAN) with the
      cingulo-opercular network (CON). In the present study, we extended this approach
      to investigate how these brain networks interact when stimulus-response mappings
      are altered by novel instructions. We hypothesized that residual stimulus
      response associations from initial practice might negatively impact the ability
      to implement novel instructions. Using functional imaging and large-scale
      connectivity analysis, we found that functional coupling between the CON and DAN
      was generally at a higher level during initial than reversal learning. Examining
      the learning-related connectivity dynamics between the CON and DAN in more detail
      by means of multivariate patterns analyses, we identified a specific subset of
      connections which showed a particularly high increase in connectivity during
      initial learning compared to reversal learning. This finding suggests that the
      CON-DAN connections can be separated into two functionally dissociable yet
      spatially intertwined subsystems supporting different aspects of short-term task
      automatization.

PMID- 29175611
TI  - Resting-state functional connectivity remains unaffected by preceding exposure to
      aversive visual stimuli.
AB  - While much is known about immediate brain activity changes induced by the
      confrontation with emotional stimuli, the subsequent temporal unfolding of
      emotions has yet to be explored. To investigate whether exposure to emotionally
      aversive pictures affects subsequent resting-state networks differently from
      exposure to neutral pictures, a resting-state fMRI study implementing a two-group
      repeated-measures design in healthy young adults (N = 34) was conducted. We
      focused on investigating (i) patterns of amygdala whole-brain and hippocampus
      connectivity in both a seed-to-voxel and seed-to-seed approach, (ii) whole-brain
      resting-state networks with an independent component analysis coupled with dual
      regression, and (iii) the amygdala's fractional amplitude of low frequency
      fluctuations, all while EEG recording potential fluctuations in vigilance. In
      spite of the successful emotion induction, as demonstrated by stimuli rating and
      a memory-facilitating effect of negative emotionality, none of the resting-state
      measures was differentially affected by picture valence. In conclusion, resting
      state networks connectivity as well as the amygdala's low frequency oscillations
      appear to be unaffected by preceding exposure to widely used emotionally aversive
      visual stimuli in healthy young adults.

PMID- 29175612
TI  - Making sense of objects lying around: How contextual objects shape brain activity
      during action observation.
AB  - Action recognition involves not only the readout of body movements and involved
      objects but also the integration of contextual information, e.g. the environment
      in which an action takes place. Notably, inferring superordinate goals and
      generating predictions about forthcoming action steps should benefit from
      screening the actor's immediate environment, in particular objects located in the
      actor's peripersonal space and thus potentially used in following action steps.
      Critically, if such contextual objects (COs) afford actions that are semantically
      related to the observed action, they may trigger or facilitate the inference of
      goals and the prediction of following actions. This fMRI study investigated the
      neural mechanisms underlying the integration of COs in semantic and spatial
      relation to observed actions. Specifically, we tested the hypothesis that the
      inferior frontal gyrus (IFG) subserves this integration. Participants observed
      action videos in which COs and observed actions had common overarching goals or
      not (goal affinity) and varied in their location relative to the actor. High goal
      affinity increased bilateral activity in action observation network nodes, i.e.
      the occipitotemporal cortex and the intraparietal sulcus, but also in the
      precuneus and middle frontal gyri. This finding suggests that the semantic
      relation between COs and actions is considered during action observation and
      triggers (rather than facilitates) processes beyond those usually involved in
      action observation. Moreover, COs with high goal affinity located close to the
      actor's dominant hand additionally engaged bilateral IFG, corroborating the view
      that IFG is critically involved in the integration of action steps under a common
      overarching goal.

PMID- 29175613
TI  - Chronic kidney disease after acute kidney injury associated with intravenous
      colistin use in survivors of severe infections: A comparative cohort study.
AB  - PURPOSE: The use of colistin for multi-drug resistant (MDR) infections has led to
      an increase of colistin-associated acute kidney injury (AKI). Nevertheless,
      information on long-term renal prognosis is scarce. We aimed to determine the
      predictors of chronic kidney disease (CKD) in survivors of MDR-infections with
      colistin-associated AKI. METHODS: A retrospective cohort of patients with
      colistin-associated AKI was compared with controls (survivors of severe
      infections who developed AKI matched by age, sex, diabetes, vancomycin exposure,
      and baseline kidney function). The primary outcome was the development of CKD
      after 6months of follow-up. RESULTS: From 2011 to 2015, 122 patients with MDR
      infections received colistin. Among 72 survivors, 29 (40%) had colistin
      associated AKI. After 6months, 22 of them (75%) progressed to CKD (G3 in 21/22)
      compared with 16 (27%) in 58 controls (P<0.001). Independent predictors of
      progression to CKD were colistin use [odds ratio (OR): 8.86; 95% CI: 2.8-27.8]
      and age (OR: 1.04, 95% CI: 1.01-1.07). In patients exposed to colistin, a total
      dose of colistin >5g was an independent predictor of progression to CKD (OR:
      14.1, 95% CI: 2.6-75.7). CONCLUSION: Colistin-associated AKI had a substantial
      risk for the latter development CKD, and consequently, these patients should be
      tightly monitored.

PMID- 29175614
TI  - To eat or not to eat-the metabolic flavor of ferroptosis.
AB  - Ferroptosis is a newly defined iron-dependent, non-apoptotic mode of cell death
      with necrotic morphology. Distinctive from other death mechanisms, ferroptosis
      requires cellular iron and lipid peroxides, and is dictated by specific cellular
      metabolic processes. Importantly, ferroptosis has been implicated in a plethora
      of human diseases. This paper reviews the recent advances and outstanding
      questions of the field by focusing on the role of cellular metabolism in
      ferroptosis. The relevance of ferroptosis to disease and therapy is also
      discussed.

PMID- 29175615
TI  - Characterization of tissue stiffness of the infraspinatus, erector spinae, and
      gastrocnemius muscle using ultrasound shear wave elastography and superficial
      mechanical deformation.
AB  - The aim of this study was to compare measurement methods of tissue stiffness
      using ultrasound shear wave elastography (SWE) and superficial mechanical
      deformation (MyotonPRO) in the infraspinatus, erector spinae, and gastrocnemius
      muscles. Thirty healthy volunteers were assessed during rest, 40% and 80% maximum
      voluntary isometric contraction (MVIC). Correlation of the two methods in the
      three muscle regions was significant (r = 0.23-0.71, p < .05), and strongest in
      the gastrocnemius. MyotonPRO reliability was excellent (ICC > 0.93), and
      demonstrated ability to discriminate between the three levels of muscle
      contraction. SWE demonstrated good reliability in the resting condition (ICC >
      0.88), but lower during the 2 MVIC conditions. The utility of SWE during
      isometric contraction may be limited due to the inability to discriminate between
      40% and 80% MVIC.

PMID- 29175616
TI  - Difficulty concentrating in generalized anxiety disorder: An evaluation of
      incremental utility and relationship to worry.
AB  - Difficulty concentrating is one of the most common diagnostic criteria across DSM
      5 categories, especially within the emotional (mood- and anxiety-related)
      disorders. A substantial literature has characterized cognitive functioning in
      emotional disorders using objective (behavioral) computerized cognitive tasks.
      However, diagnoses are typically formed on the basis of subjective (self
      reported; clinician-rated) assessments of symptoms, and little is known about
      difficulty concentrating as a symptom. These questions are particularly important
      for generalized anxiety disorder (GAD), which has long been the subject of
      nosological debates, and for which several theoretical models that suggest a
      central role for cognitive impairments (including difficulty concentrating) in
      the maintenance of psychopathology have been proposed. The present study
      evaluated the incremental utility of difficulty concentrating and its
      relationship to worry and other symptoms in 175 GAD-diagnosed adults. Clinician
      assessed difficulty concentrating incrementally predicted clinician-rated GAD,
      anxiety, and depression severity even after other GAD symptoms were controlled.
      Consistent with theoretical models of GAD that propose a direct relationship
      between worry and cognitive impairment, difficulty concentrating mediated the
      relationship between trait worry and clinical severity. These findings suggest
      that difficulty concentrating has value as a diagnostic criterion and is a
      potential mechanism by which worry increases distress and impairment.

PMID- 29175617
TI  - Bioaccessibility of PBDEs present in indoor dust: A novel dialysis membrane
      method with a Tenax TA(r) absorption sink.
AB  - Human uptake of flame retardants (FRs) such as polybrominated diphenyl ethers
      (PBDEs) via indoor dust ingestion is commonly considered as 100% bioaccessible,
      leading to potential risk overestimation. Here, we present a novel in vitro colon
      extended physiologically-based extraction test (CE-PBET) with Tenax TA(r) as an
      absorptive "sink" capable to enhance PBDE gut bioaccessibility. A cellulose-based
      dialysis membrane (MW cut-off 3.5kDa) with high pH and temperature tolerance was
      used to encapsulate Tenax TA(r), facilitating efficient physical separation
      between the absorbent and the dust, while minimizing re-absorption of the
      ingested PBDEs to the dust particles. As a proof of concept, PBDE-spiked indoor
      dust samples (n=3) were tested under four different conditions; without any Tenax
      TA(r) addition (control) and with three different Tenax TA(r) loadings (i.e.
      0.25, 0.5 or 0.75g). Our results show that in order to maintain a constant
      sorptive gradient for the low MW PBDEs, 0.5g of Tenax TA(r) are required in CE
      PBET. Tenax TA(r) inclusion (0.5g) resulted in 40% gut bioaccessibility for
      BDE153 and BDE183, whereas greater bioaccessibility values were seen for less
      hydrophobic PBDEs such as BDE28 and BDE47 (~60%). When tested using SRM 2585
      (n=3), our new Tenax TA(r) method did not present any statistically significant
      effect (p>0.05) between non-spiked and PBDE-spiked SRM 2585 treatments. Our study
      describes an efficient method where due to the sophisticated design, Tenax TA(r)
      recovery and subsequent bioaccessibility determination can be simply and reliably
      achieved.

PMID- 29175618
TI  - Human footprint in Tibet: Assessing the spatial layout and effectiveness of
      nature reserves.
AB  - Humanity is causing dramatic changes to the Earth, and we may be entering a human
      dominated era referred to as the Anthropocene. Mapping the human footprint and
      assessing the spatial layout and effectiveness of protected areas facilitate
      sustainable development. As the core region of the third pole, Tibet is an
      important area for biodiversity and the provision of ecosystem services. In this
      study, five categories of human pressure were summed cumulatively to map the
      human footprint in Tibet for 1990 and 2010, and the spatial relationship between
      the human footprint and national and provincial nature reserves (NRs) in Tibet
      was analyzed. In addition, the human footprint map was also used to evaluate the
      effectiveness of national and provincial NRs for reducing the impact of human
      activities. A comprehensive assessment was undertaken for the Yarlung Zangbo
      Grand Canyon (YZGC) NR. There were several key findings from this study. First,
      the human footprint scores (HFS) in Tibet for 1990 and 2010 were low, and
      increased by 32.35% during 1990-2010, which was greater than the global value of
      9% for 1993-2009, indicating that Tibet is seriously threatened by human
      pressure. Grazing intensity and road disturbance intensity contributed
      significantly to the increase in the HFS. Second, the average HFS for 1990 in NRs
      was lower than that for the entire Tibet, but the spatial layout and extent of
      some reserves (e.g., the Qomolangma NR) needs to be optimized further. Third, the
      establishment of NRs in Tibet was effective in reducing human activities. No
      leakage phenomena were identified in the regions surrounding the YZGC reserve.
      However, the management of NRs in Tibet is still challenging in terms of reducing
      human activities.

PMID- 29175619
TI  - Plant growth and arbuscular mycorrhizae development in oil sands processing by
      products.
AB  - Soil pollutants such as hydrocarbons can induce toxic effects in plants and
      associated arbuscular mycorrhizal fungi (AMF). This study was conducted to
      evaluate if the legume Lotus corniculatus and the grass Elymus trachycaulus and
      arbuscular mycorrhizal fungi could grow in two oil sands processing by-products
      after bitumen extraction from the oil sands in northern Alberta, Canada.
      Substrate treatments were coarse tailings sand (CTS), a mix of dry mature fine
      tailings (MFT) with CTS (1:1) and Pleistocene sandy soil (hydrocarbon free);
      microbial treatments were without AMF, with AMF and AMF plus soil bacteria
      isolated from oil sands reclamation sites. Plant biomass, root morphology, leaf
      water content, shoot tissue phosphorus content and mycorrhizal colonization were
      evaluated. Both plant species had reduced growth in CTS and tailings mix relative
      to sandy soil. AMF frequency and intensity in roots of E. trachycaulus was not
      influenced by soil hydrocarbons; however, it decreased significantly over time in
      roots of L. corniculatus without bacteria in CTS. Mycorrhizal inoculation alone
      did not significantly improve plant growth in CTS and tailings mix; however,
      inoculation with mycorrhizae plus bacteria led to a significantly positive
      response of both plant species in CTS. Thus, combined inoculation with selected
      mycorrhizae and bacteria led to synergistic effects. Such combinations may be
      used in future to improve plant growth in reclamation of CTS and tailings mix.

PMID- 29175620
TI  - Introducing the Green Protein Footprint method as an understandable measure of
      the environmental cost of anchovy consumption.
AB  - In a global framework of growing concern for food security and environmental
      protection, the selection of food products with higher protein content and lower
      environmental impact is a challenge. To assess the reliability of different
      strategies along the food supply chain, a measure of food cost through the
      environmental impact-protein content binomial is necessary. This study proposes a
      standardized method to calculate the Green Protein Footprint (GPF) index, a
      method that assesses both the environmental impact of a food product and its
      protein content provided to consumers. Life Cycle Assessment (LCA) was used to
      calculate the environmental impact of the selected food products, and a Life
      Cycle Protein Assessment (LCPA) was performed by accounting for the protein
      content along the supply chain. Although the GPF can be applied to all food chain
      products, this paper is focused on European anchovy-based products for indirect
      human consumption (fishmeal) and for direct human consumption (fresh, salted and
      canned anchovies). Moreover, the circular economy concept was applied considering
      the valorization of the anchovy residues generated during the canning process.
      These residues were used to produce fishmeal, which was employed in bass
      aquaculture. Hence, humans are finally consuming fish protein from the residues,
      closing the loop of the original product life cycle. More elaborated, multi
      ingredient food products (salted and canned anchovy products), presented higher
      GPF values due to higher environmental impacts. Furthermore, the increase of food
      loss throughout their life cycle caused a decrease in the protein content.
      Regarding salted and canned products, the packaging was the main hotspot. The
      influence of the packaging was evaluated using the GPF, reaffirming that plastic
      was the best alternative. These results highlighted the importance of improving
      packaging materials in food products.

PMID- 29175621
TI  - Effects of soil type and rainfall intensity on sheet erosion processes and
      sediment characteristics along the climatic gradient in central-south China.
AB  - Soil erosion poses a major threat to the sustainability of natural ecosystems.
      The main objective of this study was to investigate the effects of soil type and
      rainfall intensity on sheet erosion processes (hydrological, erosional processes
      and sediment characteristics) from temperate to tropical climate. Field plot
      experiments were conducted under pre-wetted bare fallow condition for five soil
      types (two Luvisols, an Alisol, an Acrisol and a Ferralsol) with heavy textures
      (silty clay loam, silty clay and clay) derived separately from loess deposits,
      quaternary red clays and basalt in central-south China. Rainfall simulations were
      performed at two rainfall intensities (45 and 90mmh-1) and lasted one hour after
      runoff generation. Runoff coefficient, sediment concentration, sediment yield
      rate and sediment effective size distribution were determined at 3-min intervals.
      Runoff temporal variations were similar at the high rainfall intensity, but
      exhibited a remarkable difference at the low rainfall intensity among soil types
      except for tropical Ferralsol. Illite was positively correlated with runoff
      coefficient (p<0.05). Rainfall intensity significantly contributed to the
      erosional process (p<0.001). Sediment concentration and yield rate were the
      smallest for the tropical Ferralsol and sediment concentration was the largest
      for the temperate Luvisol. The regimes (transport and detachment) limiting
      erosion varied under the interaction of rainfall characteristics (intensity and
      duration) and soil types, with amorphous iron oxides and bulk density jointly
      enhancing soil resistance to erosive forces (Adj-R2>88%, p<0.001). Sediment size
      was dominated by <0.1mm size fraction for the Luvisols and bimodally distributed
      with the peaks at <0.1mm and 1-0.5mm size for the other soil types. Exchangeable
      sodium decreased sediment size while rainfall intensity and clay content
      increased it (Adj-R2=96%, p<0.01). These results allow to better understand the
      climate effect on erosion processes at the spatial-temporal scale from the
      perspective of soil properties.

PMID- 29175622
TI  - Methylated arsenic species throughout a 4-m deep core from a free-floating peat
      island.
AB  - Arsenic (As) occurs in soils mostly in inorganic forms, whereas the organic forms
      usually occur only in trace amounts. Peatlands are waterlogged, generally anoxic,
      organic soils representing the first step in coal formation; the contribution of
      organic vs. inorganic As species in this environment has received little research
      attention. Here, 57 peat samples collected throughout a 4-m deep, free-floating
      mire were analysed for total As and for its organic species, including
      dimethylarsinic acid (DMA), methylarsonic acid (MA), trimethylarsine oxide (TMAO)
      and arsenobetaine (AB), by HPLC-ICPMS. Aqueous trifluoroacetic acid was used as
      extractant, resulting in an average extraction efficiency of almost 80%. Total As
      concentration throughout the profile ranged between 0.2 and 9.8mg/kgpeat (mean:
      1.4+/-1.2mg/kgpeat). Organic As species (DMA+MA+TMAO+AB) accounted, on average,
      for 28+/-10% of total As (range: 6-51%), and for 37+/-13% of the extracted As
      (range: 7-64%). The relative abundance of organoarsenicals generally followed the
      order DMA>TMAO~MA?AB. A positive correlation (p<0.001) was found among all
      organic As compounds, whereas their concentrations were negatively correlated
      with total sulfur content. The submerged zone (bottom 300cm) showed average and
      maximum concentrations of organoarsenic compounds that were almost twice those
      found in the top 100cm. This study shows that significant proportions of
      methylated As species occur even in peat samples characterized by low total As
      concentration (mostly <2mg/kg). Finally, this work provides the first evidence of
      organoarsenic species in free-floating mires, i.e., a globally distributed but
      scarcely investigated ecosystem.

PMID- 29175623
TI  - Evidence from SINPHONIE project: Impact of home environmental exposures on
      respiratory health among school-age children in Romania.
AB  - BACKGROUND: Exposure to indoor air pollutants at home was found to be associated
      with respiratory diseases. As lifestyle changes with rapid economic growth in
      Romania, the aim of our study is to describe the characteristics of Romanian
      homes and their impact on children's respiratory health. METHODS: Self-reported
      information on respiratory symptoms was collected from 280 Romanian elementary
      school students in 2011, and the symptoms were categorized into allergy, asthma
      like, and flu-like symptoms. Home characteristics and demographic information
      were collected from questionnaires answered by parents. The association between
      home characteristics and respiratory health was assessed through multivariate
      logistic regression controlling for school indoor exposure. RESULTS: As compared
      to U.S. households, Romanian homes have a higher percentage of smokers, limited
      use of indoor climate control, and higher use of iron stoves. Exposure to
      environmental tobacco smoke was associated with both asthma and allergy symptoms.
      Additional risk factors identified for allergy symptoms include living in
      apartments, near pesticide sprayed areas, and the use of incense sticks. The
      significantly higher risk of flu-like symptoms was associated with mold and
      dampness issues, the use of air conditioner, gas heater/iron stove in children's
      bedroom. CONCLUSION: Our findings suggest that an increase in respiratory
      symptoms among Romanian school-age children can be partly related to their
      environmental exposure at home. Since most of the identified risk factors are
      preventable, our results provide critical information and evidence for
      policymakers, to develop target intervention and education strategies.

PMID- 29175624
TI  - Copper isotopic record in soils and tree rings near a copper smelter, Copperbelt,
      Zambia.
AB  - The copper (Cu) content and isotopic composition were studied in soils and in
      pine tree rings at locations close to and far from the Cu smelter, located at
      Kitwe, Zambia. The soil in the remote area contained 25-75mgkg-1 Cu, whereas the
      soil close to the smelter contained 207-44,000mgkg-1 Cu. The delta65Cu at the
      remote area and close to the smelter varied in the range -0.40 to -0.110/00, and 
      0.44 to 0.010/00 respectively. The delta65Cu of the surface soil at both profiles
      (-0.44 to -0.400/00) is similar to the isotopic composition of the concentrates
      processed in the smelter (-0.75 to -0.450/00), i.e. both locations are affected
      by Cu ore dust. The increase in the delta65Cu in the direction towards the centre
      of the profile is caused by the oxidative dissolution of Cu(I) from ore minerals,
      during which heavier Cu is released. In deeper parts of the profile, there is a
      slight decrease in delta65Cu because of easier mobilisation of the lighter
      isotope. The tree rings at the two locations differ in the total contents and
      isotopic composition. At the less contaminated site, the Cu contents equal 0.4 to
      1.1mgkg-1 while, at the polluted site, the Cu contents vary in the range 3 to
      47mgkg-1. Whereas, at the less contaminated location, the tree rings are
      substantially enriched in lighter Cu (delta65Cu=-0.76 to -2.20/00), at locations
      close to the smelter the tree rings have an isotopic composition (-0.31 to 
      0.880/00) similar to that of the contaminated soil or processed ore. The isotopic
      compositions of the tree rings close to the smelter are affected particularly by
      interception of dust containing Cu ore. The delta13C in tree rings demonstrate
      the interconnection of acidification and Cu mobility.

PMID- 29175626
TI  - Modeling the pathology, immune responses, and kinetics of HSV-1 replication in
      the lip scarification model.
AB  - The lip scarification model of herpes simplex virus type 1 (HSV-1) infection can
      be used to study acute infection in the orofacial tissue and the establishment of
      viral latency. In this study, mice were inoculated with HSV-1 and tissue
      harvested during the acute phase of infection. Clinical presentation of classical
      open sores on the lip of infected mice was observed. We defined the
      histopathology, disease scores, and immune infiltration of the lower lip during
      the formation and resolution of the clinical lesions. Finally, the kinetics of
      virus replication and transport of viral genomes to the trigeminal ganglia were
      established. With the virological and pathologic events of acute infection
      defined, the HSV-1 lip scarification model can now be used to study primary HSV-1
      infection, invasion of the trigeminal ganglia, and establishment of latency.

PMID- 29175627
TI  - Establishment of robust HCV genotype 4d, 5a, and 6a replicon systems.
AB  - Hepatitis C Virus (HCV) is a diverse human pathogen which displays ~15%
      divergence at the subtype level. To facilitate development of antivirals with pan
      genotype activity, we developed the first genotype 4d subgenomic replicon, as
      well as new replicons for genotypes 5a, and 6a. Adaptive mutations developed in
      these replicons differ greatly across genotypes. Their impacts on the replication
      capacity were tested using site-directed mutants. In the genotype 4d replicon,
      single mutations have moderate effect, but the double mutation NS4A-Q34R+NS5A
      S232G increased the replication capacity by 161-fold. These new stable replicon
      cell lines were used to determine the antiviral activity of HCV inhibitors. The
      NS3 protease inhibitor voxilaprevir, NS5A second generation inhibitor
      velpatasvir, and NS5B nucleoside analog inhibitor sofosbuvir, had similar
      antiviral activities across the different genotypes/subtypes tested, while the
      NS5A first generation inhibitor, ledipasvir, had very good antiviral activity
      against GT1, 4, 5, and 6 in vitro.

PMID- 29175625
TI  - Increased surface expression of HIV-1 envelope is associated with improved
      antibody response in vaccinia prime/protein boost immunization.
AB  - HIV-1 envelope (Env)-based vaccines have so far largely failed to induce
      antibodies that prevent HIV-1 infection. One factor proposed to limit the
      immunogenicity of cell-associated Env is its low level of expression on the cell
      surface, restricting accessibility to antibodies. Using a vaccinia prime/protein
      boost protocol in mice, we explored the immunologic effects of mutations in the
      Env cytoplasmic tail (CT) that increased surface expression, including partial
      truncation and ablation of a tyrosine-dependent endocytosis motif. After vaccinia
      primes, CT-modified Envs induced up to 7-fold higher gp120-specific IgG, and
      after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1
      neutralizing antibody titers, although results were variable between isolates.
      These data indicate that the immunogenicity of HIV-1 Env in a prime/boost vaccine
      can be enhanced in a strain-dependent manner by CT mutations that increase Env
      surface expression, thus highlighting the importance of the prime in this vaccine
      format.

PMID- 29175628
TI  - Neuronal death/apoptosis induced by intracellular zinc deficiency associated with
      changes in amino-acid neurotransmitters and glutamate receptor subtypes.
AB  - In the present study, a model of zinc deficiency was developed by exposing
      primary neurons to an N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN)
      containing medium. The cell survival rate, apoptosis rate, intracellular and
      extracellular concentrations of 4 amino acids, and the expression of 2 glutamate
      receptor subtypes alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor
      (GluR2)and N-methyl-d-aspartate receptor subtype 2B (NR2B) were evaluated in zinc
      deficient cells. The results revealed that zinc deficiency led to a decrease in
      cell viability and an increase in the apoptosis rate. Additionally, in cultured
      neurons, zinc deficiency led to an increase in the concentration of aspartic acid
      (Asp) and a decrease in the concentrations of glutamate (Glu), glycine (Gly), and
      gamma-aminobutyric acid (GABA). These changes were reversed by concurrent zinc
      supplementation. Furthermore, zinc deficiency led to an increase in the secreted
      amounts of Glu, Gly, and Asp but a decrease in secreted amounts of GABA, as
      measured using the concentrations of these amino acids in the cell-culture
      medium. These changes were partially reversed by zinc supplementation. Finally,
      zinc deficiency led to a significant decrease in GluR2 expression and an increase
      in NR2B expression in cultured neurons, whereas simultaneous treatment with zinc
      sulfate (ZnSO4) prevented these changes. These results suggest that zinc
      deficiency-induced neuronal death/apoptosis involves changes in the
      concentrations of 4 amino acid neurotransmitters and the expression of 2
      glutamate receptor subtypes.

PMID- 29175629
TI  - Effects of polar substituents on the biological activity of thiosemicarbazone
      metal complexes.
AB  - In this paper, citronellal, vanillin and pyridoxal thiosemicarbazones were
      modified with polar substituents, namely ethylmorpholine and glucose, to increase
      their polarity and compare the effects of these moieties on their biological
      activity. Altogether, nine ligands were synthesized and for each of them also
      their copper(II) and nickel(II) complexes were prepared and used for the
      biological tests. Eventually, assays on proliferation inhibition were conducted
      using leukemic cell line U937, already used as a model for previous citronellal
      thiosemicarbazone tests. Biological tests were also performed on solid tumor cell
      line HT29. From the first screenings, two of the metal complexes showed
      remarkable interesting properties, and, therefore, were also tested for
      histosensitivity.

PMID- 29175630
TI  - Predicting Treatment Response of Breast Cancer to Neoadjuvant Chemotherapy Using
      Ultrasound-Guided Diffuse Optical Tomography.
AB  - PURPOSE: To prospectively investigate ultrasound-guided diffuse optical
      tomography (US-guided DOT) in predicting breast cancer response to neoadjuvant
      chemotherapy (NAC). MATERIALS AND METHODS: Eighty-eight breast cancer patients,
      with a total of 93 lesions, were included in our study. Pre- and post-last
      chemotherapy, size and total hemoglobin concentration (THC) of each lesion were
      measured by conventional US and US-guided DOT 1 day before biopsy (time point t0,
      THC THC0, SIZE S0) and 1 to 2 days before surgery (time point tL, THCL, SL). The
      relative changes in THC and SIZE of lesions after the first and last NAC cycles
      were considered as the variables DeltaTHC and DeltaSIZE. Receiver operating
      characteristic curve was performed to calculate DeltaTHC and DeltaSIZE cutoff
      values to evaluate pathologic response of 93 breast cancers to NAC, which were
      then prospectively used to predicate response of 61 breast cancers to NAC.
      RESULTS: The cutoff values of DeltaTHC and DeltaSIZE for evaluation of breast
      cancers NAC treatment response were 23.9% and 42.6%. At DeltaTHC 23.9%, the
      predicted treatment response in 61 breast lesions for the time points t1 to t3
      was calculated by area under the curve (AUC), which were AUC1 0.534 (P=.6668),
      AUC2 0.604 (P=.1893), and AUC3 0.674(P =. 0.027), respectively; for DeltaSIZE
      42.6%, at time points t1 to t3, AUC1 0.505 (P=.9121), AUC2 0.645 (P=.0115), and
      AUC3 0.719 (P=.0018). CONCLUSION: US-guided DOT DeltaTHC 23.9% and US DeltaSIZE
      42.6% can be used for the response evaluation and earlier prediction of the
      pathological response after three rounds of chemotherapy.

PMID- 29175631
TI  - The inhibitory effect of chitosan oligosaccharides on beta-site amyloid precursor
      protein cleaving enzyme 1 (BACE1) in HEK293 APPswe cells.
AB  - Amyloid precursor protein (APP) proteolysis is essential for the production of
      beta-amyloid peptides (Abeta) that form senile plaques in Alzheimer's disease
      (AD) brains. The beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) is
      the rate limiting enzyme in the generation of Abeta from APP, inhibition of BACE1
      is thereby considered as an attractive strategy for anti-AD drug discovery.
      Chitosan oligosaccharides (COS) has been shown to possess various biological
      activities. Here we investigated the potential inhibitory effect of COS on both
      BACE1 expression in HEK293 APPswe cells and BACE1 enzymatic activity in vitro.
      The results showed that COS (100-500MUg/ml) dose-dependently decreased the cell
      apoptosis, and potently repressed the secretion of both Abeta40 and Abeta42 as
      determined by ELISA. Moreover, treatment with COS resulted in a dramatic
      reduction in BACE1 mRNA and protein expression level, eIF2alpha phosphorylation
      as well as BACE1 enzymatic activity. Taken together, our findings indicate that
      COS can ameliorate Abeta-associated neurotoxicity, which may be, at least in
      part, attributable to reductions in BACE1 enzymatic activity and expression.

PMID- 29175632
TI  - Intravenous administration of the adeno-associated virus-PHP.B capsid fails to
      upregulate transduction efficiency in the marmoset brain.
AB  - Intravenous administration of adeno-associated virus (AAV)-PHP.B, a capsid
      variant of AAV9 containing seven amino acid insertions, results in a greater
      permeability of the blood brain barrier (BBB) than standard AAV9 in mice, leading
      to highly efficient and global transduction of the central nervous system (CNS).
      The present study aimed to examine whether the enhanced BBB penetrance of AAV
      PHP.B observed in mice also occurs in non-human primates. Thus, a young adult
      (age, 1.6 years) and an old adult (age, 7.2 years) marmoset received an
      intravenous injection of AAV-PHP.B expressing enhanced green fluorescent protein
      (EGFP) under the control of the constitutive CBh promoter (a hybrid of
      cytomegalovirus early enhancer and chicken beta-actin promoter). Age-matched
      control marmosets were treated with standard AAV9-capsid vectors. The animals
      were sacrificed 6 weeks after the viral injection. Based on the results, only
      limited transduction of neurons (0-2%) and astrocytes (0.1-2.5%) was observed in
      both AAV-PHP.B- and AAV9-treated marmosets. One noticeable difference between AAV
      PHP.B and AAV9 was the marked transduction of the peripheral dorsal root ganglia
      neurons. Indeed, the soma and axons in the projection from the spinal cord to the
      nucleus cuneatus in the medulla oblongata were strongly labeled with EGFP by AAV
      PHP.B. Thus, except for the peripheral dorsal root ganglia neurons, the AAV-PHP.B
      transduction efficiency in the CNS of marmosets was comparable to that of AAV9
      vectors.

PMID- 29175633
TI  - DL-3-n-butylphthalide alleviates vascular cognitive impairment induced by chronic
      cerebral hypoperfusion by activating the Akt/Nrf2 signaling pathway in the
      hippocampus of rats.
AB  - Oxidative stress induced by chronic cerebral hypoperfusion (CCH) plays an
      important role in the pathogenesis of vascular cognitive impairment (VCI). The
      Akt/Nrf2 signaling pathway is one of the most important antioxidative stress
      pathways. To explore whether NBP (DL-3-n-butylphthalide) could alleviate VCI
      induced by CCH via activating the Akt/Nrf2 signaling pathway and modifying the
      levels of apoptosis-related proteins, adult male Sprague-Dawley rats were
      subjected to permanent occlusion of bilateral common carotid arteries (BCCAO) and
      treated either with vehicle or NBP (applied in two doses, 40 mg/kg and 80 mg/kg)
      while sham operated animals were treated with vehicle. Treatments were
      administered daily for 28 days. The obtained results indicate that both
      administrated doses of NBP significantly ameliorated the spatial learning and
      memory impairments as indicated by the Morris water maze test while Hematoxylin
      Eosin staining revealed that morphological defects in the CA1 area of hippocampus
      were improved. Moreover, NBP reversed the BCCAO-induced downregulation of
      investigated oxidative stress-related proteins (p-Akt, t-Nrf2, n-Nrf2 and HO-1)
      along with the upregulation of pro-apoptotic molecule, Bax and reduction of the
      expression of anti-apoptotic protein, Bcl-2. According to presented results, NBP
      may have a protective effect against cognitive and morphological impairments
      induced by CCH via activation of Akt/Nrf2 signaling pathway and inhibition of
      apoptotic cascade.

PMID- 29175634
TI  - Barrier-relevant crash modification factors and average costs of crashes on
      arterial roads in Indiana.
AB  - The objective of this study was to develop crash modification factors (CMFs) and
      estimate the average crash costs applicable to a wide range of road-barrier
      scenarios that involved three types of road barriers (concrete barriers, W-beam
      guardrails, and high-tension cable barriers) to produce a suitable basis for
      comparing barrier-oriented design alternatives and road improvements. The
      intention was to perform the most comprehensive and in-depth analysis allowed by
      the cross-sectional method and the crash data available in Indiana. To accomplish
      this objective and to use the available data efficiently, the effects of barrier
      were estimated on the frequency of barrier-relevant (BR) crashes, the types of
      harmful events and their occurrence during a BR crash, and the severity of BR
      crash outcomes. The harmful events component added depth to the analysis by
      connecting the crash onset with its outcome. Further improvement of the analysis
      was accomplished by considering the crash outcome severity of all the individuals
      involved in a crash and not just drivers, utilizing hospital data, and pairing
      the observations with and without road barriers along same or similar road
      segments to better control the unobserved heterogeneity. This study confirmed
      that the total number of BR crashes tended to be higher where medians had
      installed barriers, mainly due to collisions with barriers and, in some cases,
      with other vehicles after redirecting vehicles back to traffic. These undesirable
      effects of barriers were surpassed by the positive results of reducing cross
      median crashes, rollover events, and collisions with roadside hazards. The
      average cost of a crash (unit cost) was reduced by 50% with cable barriers
      installed in medians wider than 50ft. A similar effect was concluded for concrete
      barriers and guardrails installed in medians narrower than 50ft. The studied
      roadside guardrails also reduced the unit cost by 20%-30%. Median cable barriers
      were found to be the most effective among all the studied barriers due to the
      smaller increase in the crash frequency caused by these barriers and the less
      severe injury outcomes. More specifically, the occupants of vehicles colliding
      with near-side cable barriers tended to have less severe injuries than occupants
      of vehicles entering the median from median's farther side. The near-side cable
      barriers provided protection against rollover inside the median and against a
      potentially dangerous collision with or running over the median drain; therefore,
      the greatest safety benefit can be expected where cable barriers are installed at
      both edges of the median. The CMFs and unit crash costs for 48 road-barrier
      scenarios produced in this study are included in this paper.

PMID- 29175635
TI  - Correlates of fatality risk of vulnerable road users in Delhi.
AB  - Pedestrians, cyclists, and users of motorised two-wheelers account for more than
      85% of all the road fatality victims in Delhi. The three categories are often
      referred to as vulnerable road users (VRUs). Using Bayesian hierarchical approach
      with a Poisson-lognormal regression model, we present spatial analysis of road
      fatalities of VRUs with wards as areal units. The model accounts for spatially
      uncorrelated as well as correlated error. The explanatory variables include
      demographic factors, traffic characteristics, as well as built environment
      features. We found that fatality risk has a negative association with socio
      economic status (literacy rate), population density, and number of roundabouts,
      and has a positive association with percentage of population as workers, number
      of bus stops, number of flyovers (grade separators), and vehicle kilometers
      travelled. The negative effect of roundabouts, though statistically
      insignificant, is in accordance with their speed calming effects for which they
      have been used to replace signalised junctions in various parts of the world.
      Fatality risk is 80% higher at the density of 50 persons per hectare (pph) than
      at overall city-wide density of 250 pph. The presence of a flyover increases the
      relative risk by 15% compared to no flyover. Future studies should investigate
      the causal mechanism through which denser neighborhoods become safer. Given the
      risk posed by flyovers, their use as congestion mitigation measure should be
      discontinued within urban areas.

PMID- 29175636
TI  - Effects of Rhizophagus clarus and P availability in the tolerance and
      physiological response of Mucuna cinereum to copper.
AB  - Arbuscular mycorrhizal fungi (AMF) improve plant ability to uptake P and tolerate
      heavy metals. This study aimed to evaluate the effect of available P and the
      inoculation of Rhizophagus clarus in a Cu-contaminated soil (i) on the activity
      of acid phosphatases (soil and plant), the presence of glomalin, and (ii) in the
      biochemical and physiological status of Mucuna cinereum. A Typic Hapludalf soil
      artificially contaminated by adding 60 mg kg-1 Cu was used in a 3 * 2 factorial
      design with three replicates. Treatments consisted of three P levels: 0, 40, and
      100 mg kg-1 P. Each P treatment level was inoculated (+AMF)/non-inoculated (-AMF)
      with 200 spores of R. clarus per pot, and plants grown for 45 days. The addition
      of at least 40 mg kg-1 P and the inoculation of plants with R. clarus proved to
      be efficient to reduce Cu phytotoxicity and increase dry matter yield.
      Mycorrhization and phosphate fertilization reduced the activity of enzymes
      regulating oxidative stress (SOD and POD), and altered the chlorophyll a
      fluorescence parameters, due to the lower stress caused by available Cu. These
      results suggest a synergism between the application of P and the inoculation with
      R. clarus, favoring the growth of M. cinereum in a Cu-contaminated soil. This
      study shows that AMF inoculation represents an interesting alternative to P
      fertilization to improve plant development when exposed to excess Cu.

PMID- 29175637
TI  - Pectin and cellulose cell wall composition enables different strategies to leaf
      water uptake in plants from tropical fog mountain.
AB  - Leaf water uptake (LWU) has been observed in plants of different ecosystems and
      this process is distinct among different species. Four plant species from the
      Brazilian fog mountain fields were evaluated in order to detect if leaf water
      uptake capacity is related to the cell wall composition of leaf epidermis. LWU
      measurements and their relation to anatomical and biochemical traits were
      analyzed. Cell wall composition was verified through immunocytochemistry using
      monoclonal antibodies recognizing pectin compounds, and histochemistry with
      calcofluor white to track cellulose. Differences in LWU among the four species
      were clearly revealed. Two species presented higher maximum leaf water content
      and the lowest values of water absorption speed. The other two species presented
      opposite behavior, namely, low leaf water uptake and the highest values of water
      absorption speed. The anatomical traits associated with the cell wall composition
      corroborated the data on the different LWU strategies. The species with abundant
      detection of cellulose in their epidermal cell walls absorbed more water, but
      more slowly, while those with abundant detection of pectins absorbed water at a
      higher speed. These results indicate that cell wall composition regarding pectin
      and cellulose are significant for water uptake by the leaf epidermis. Pectin
      provides greater porosity and absorption speed, while cellulose provides greater
      hydrophilicity and greater water uptake capacity. Current data indicate that the
      composition of epidermal cell walls is a relevant trait for leaf water uptake.

PMID- 29175638
TI  - Links between gendered leisure time in childhood and adolescence and gendered
      occupational aspirations.
AB  - The world of work remains gender-segregated, and research is needed to identify
      factors that may give rise to women's and men's vocational choices. This study
      explored bidirectional relations between youth's gendered career aspirations and
      the proportions of youth's leisure time spent in stereotypically gendered
      activities and gendered social contexts. Participants were 203 youth (52% girls)
      from predominantly white, working and middle class families living in the US, who
      reported on their occupational aspirations and gendered interests in home
      interviews and on their daily activities in a series of 7 nightly phone
      interviews on two occasions, in middle childhood (Mage = 10.9) and in adolescence
      (Mage = 17.3). Path models revealed that aspirations predicted youth's time use
      more so than the reverse. Time in gendered social contexts, specifically time in
      female-only contexts, but not time in gender-typed activities, predicted career
      aspirations. Implications of these findings and suggestions for future research
      are discussed.

PMID- 29175639
TI  - Joint mechanical asymmetries during low- and high-demand mobility tasks:
      Comparison between total knee arthroplasty and healthy-matched peers.
AB  - Chronic inter-limb joint mechanical asymmetry has been reported following total
      knee arthroplasty (TKA) during low-demand mobility tasks such as level walking.
      However, no study has compared the inter-limb asymmetry during a high-demand
      mobility task such as decline walking. The objective of this cross-sectional
      study was to compare inter-limb asymmetry differences during both level and
      decline walking tasks at six months following TKA compared to asymmetry present
      in an age, gender, body mass index and activity level matched healthy cohort.
      Kinetic and kinematic gait analysis was conducted on 42 patients with TKA and 15
      healthy-matched peers. Our inter-limb asymmetry results demonstrated
      significantly (p<0.05) greater combined limb support moment (MS) (mean
      differences [MD]=0.17; 95% CI=0.07, 0.22), knee extensor moment (MK) (MD=0.05;
      95% CI=0.02, 0.09) and vertical ground reaction force (vGRF) (MD=0.03; 95%
      CI=0.01, 0.08) differences during decline walking compared to level walking in
      patients with TKA. Greater MS (MD=0.24; 95% CI=0.13, 0.35), MK (MD=0.08; 95%
      CI=0.03, 0.18), vGRF (MD=0.04; 95% CI=0.01, 0.08) and knee joint angle (MD=2.4;
      95% CI=0.37, 3.80) differences were present in patients with TKA compared to
      healthy-matched peers during decline walking. Greater MS (MD=0.13; 95% CI=0.05,
      0.20) and plantarflexor moment (MD=0.06; 95% CI=0.04, 0.16) differences were
      present in patients with TKA compared to healthy-matched peers during level
      walking. Post-TKA inter-limb asymmetry during level walking worsens as the
      physical demands of the task are increased. Thus, even patients with good self
      reported outcomes after TKA exhibit substantial deficits in their mobility
      reserves that could limit their independence and community mobility as they age.

PMID- 29175640
TI  - An exploratory study examining factors underpinning postural instability in older
      adults with idiopathic neck pain.
AB  - There is limited understanding of potential mechanisms underpinning postural
      control deficits in people with neck pain. This study examined several
      characteristics that might explain impaired postural stability in a group of
      older adults with neck pain, and compared the results in this cohort with that of
      asymptomatic controls. In this cross-sectional study we compared physical
      activity, lower limb motor and sensory function, vestibular and visual function,
      falls efficacy and dizziness handicap in 84 older adults with (n=35, age 69.6+/
      6.3) and without (n=49, age 69.4+/-4.7) idiopathic neck-pain. Additionally,
      dynamic balance was assessed using the dynamic gait index (DGI) and standard and
      wavelet analysis of static balance was computed after data capture. Physical
      activity levels, lower limb motor and sensory function, vestibular function and
      visual contrast sensitivity were not different between groups (p>0.05). The neck
      pain group demonstrated higher falls efficacy (p=0.01), greater levels of
      dizziness handicap (p<0.01), and higher CoP velocity measures in the moderate
      (1.56-6.25Hz) and low (0.39-1.56Hz) frequency bandwidths. Our results suggest
      that neck-pain induced postural control deficits in older adults may not be
      associated with the physical activity levels, lower limb motor and sensory
      function, or vestibular and visual function. Inferring from wavelet analysis
      results, we speculated that sensory re-weighting may have occurred to compensate
      for the deficits in neck proprioception. Further research is warranted to
      determine neck specific mechanisms underpinning postural control dysfunction in
      neck pain.

PMID- 29175641
TI  - Effect of tibia marker placement on knee joint kinematic analysis.
AB  - Variability of kinematic measures determined by different marker sets among sites
      participating in a collaborative study is necessary for determining the
      reliability of a multi-site gait analysis research. We compared knee kinematics
      based on different marker sets on the tibia, calculating by segmental
      optimization (SO) and multi-body optimization (MBO) methods respectively, in
      order to assess the effect of marker locations on the methods. 11 healthy
      subjects participated in the study with 33 markers attached to the lower
      extremity segments, and 4 groups were identified according to markers on the
      tibia. Knee joint kinematics during level walking were measured and then compared
      among the 4 groups using statistical parametric mapping. For SO method, the
      results showed that there were no significant differences in the knee joint
      angles when used different marker sets on the tibia. However, significant
      differences were found in the transverse plane kinematics for MBO method. It was
      concluded that MBO method was more likely to be influenced by different marker
      sets. More attention should be paid to marker sets, specifically for MBO method,
      when three-dimensional gait analysis data are shared and interpreted among sites
      for clinical decision-making.

PMID- 29175642
TI  - A simple and rapid measurement method of encapsulation efficiency of doxorubicin
      loaded liposomes by direct injection of the liposomal suspension to liquid
      chromatography.
AB  - A simple and rapid chromatographic measurement method for determining doxorubicin
      (DOX) encapsulation efficiency (EE) into PEGylated liposomes using nanoparticle
      exclusion chromatography (nPEC) was developed. In this work, Doxil(r) and two
      PEGylated liposomes spiked with DOX were employed as model liposomes, and
      unencapsulated DOX was measured by high performance liquid chromatography with
      diode-array detector using an N-vinylpyrrolidone modified nPEC column without any
      sample pretreatment. Only 5 MUL of an intact liposomal suspension and 3 min
      analysis time were required for the determination of the quantity of
      unencapsulated DOX. The method was validated in terms of linearity, accuracy,
      precision, and recovery in the range from 0.00-1.0 mg/mL (corresponding to 100
      50% EE). Applicability of the method was confirmed using the measurement of time
      dependent DOX loading% into the liposomes with the remote loading method using an
      ammonium sulfate gradient. Furthermore, it was found that the peak area of DOX
      loaded liposomes in the chromatogram was proportional to DOX EE%. As this simple
      and rapid analytical method can measure the EE precisely, it is expected that
      this method will be applicable to the in-process control of liposome preparation
      manufacturing and the quality control of the liposome drug products.

PMID- 29175643
TI  - Sustained-release multiparticulates for oral delivery of a novel peptidic ghrelin
      agonist: Formulation design and in vitro characterization.
AB  - There is an impetus to provide appropriate sustained release oral delivery
      vehicles to protect biofunctional peptide loads from gastric degradation in vivo.
      This study describes the generation of a high load capacity pellet formulation
      for sustained release of a freely water-soluble dairy-derived hydrolysate, FHI
      2571. The activity of this novel peptidic ghrelin receptor agonist is reported
      using in vitro calcium mobilization assays. Conventional extrusion spheronization
      was then used to prepare peptide-loaded pellets which were subsequently coated
      with ethylcellulose (EC) film coats using a fluid bed coating system in bottom
      spray (Wurster) mode. Aqueous-based EC coating dispersions produced mechanically
      brittle coats which fractured due to osmotic pressure build-up within pellets in
      simulated media. In contrast, an ethanolic-based EC coating solution provided
      robust, near zero-order release in both USP Type 1 and Type 4 dissolution
      studies. Interestingly, the functionality of aqueous-based EC film coats was
      restored by first layering pellets with a methacrylic acid copolymer (MA)
      subcoat, thereby hindering pellet core swelling in acidic media. Broadband
      Acoustic Resonance Dissolution Spectroscopy (BARDS) was utilised as a
      complementary technique to confirm the results seen in USP dissolution studies.
      Retention of activity of the ghrelinergic peptide hydrolysate in the final
      encapsulated product was confirmed as being greater than 80%. The described
      pellet formulation is amenable to oral dosing in small animal studies in order to
      assess in vivo efficacy of the whey-derived ghrelinergic hydrolysate. In more
      general terms, it is also suitable as a delivery vehicle for peptide-based
      bioactives to special population groups e.g paediatric and geriatric.

PMID- 29175644
TI  - Active freeze drying for production of nanocrystal-based powder: A pilot study.
AB  - Active Freeze Drying allows for producing lyophilised powders by progressive
      agitation of frozen blocks undergoing sublimation. One potential application of
      this process is the formulation design of unstable nanosuspensions for oral drug
      delivery, as here shown for nanocrystal-based ketoconazole powder. With this
      technique, a critical vapour flow needs to be achieved in order to obtain
      reasonable process yields (>78%). The size distribution of powder particles
      (median size between 21 and 44 MUm) was affected by the nanocrystal concentration
      and the drug-to-stabilizer ratio. This was assumed to be related to the
      mechanical strength of the solid network from which the powder particles break
      off. The adjustments of the drug-to-stabilizer ratio and the freezing procedure
      proved to play a major role in improving powder redispersibility. However,
      differences in powder redispersibility did not translate into significant changes
      in in-vitro dissolution rates. Active Freeze Drying has confirmed to be a
      promising tool to efficiently produce redispersible nanocrystal powders.

PMID- 29175645
TI  - Multivariate analysis for the optimization of microfluidics-assisted
      nanoprecipitation method intended for the loading of small hydrophilic drugs into
      PLGA nanoparticles.
AB  - Design of Experiment-assisted evaluation of critical process (total flow rate,
      TFR, flow rate ratio, FRR) and formulation (polymer concentration and structure,
      drug:polymer ratio) variables in a novel microfluidics-based device, a staggered
      herringbone micromixer (SHM), for poly(lactic-co-glycolic acid) copolymer (PLGA)
      nanoparticles (NPs) manufacturing was performed in order to systematically
      evaluate and mathematically describe their effects on NPs sizes and drug
      encapsulation; a small hydrophilic moiety, N-acetylcysteine, was chosen as
      challenging model drug. SHM-assisted nanoprecipitation method consistently
      yielded NPs with tailor made sizes (in the range of 100-900 nm) and
      polydispersity index range from 0.061 to 0.286. Significant effects on NPs sizes
      were highlighted for TFR and FRR: increasing TFR (from 5 to 15 mL/min) and
      decreasing FRR (from 1:1 to 1:5 v/v, acetonitrile: buffer) NPs with mean diameter
      <200 nm were obtained. SHM technique allowed for flexible, application-specific
      tuning of PLGA NPs size using organic solvents with relatively low toxicity
      (acetone, acetonitrile), varying aqueous phase composition (Tris buffer vs PVA
      aqueous solution) and PLGA characteristics (Mw ranging from 25-90 kDa, capped or
      un-capped PLGA, different lactide:glycolide molar ratio). A very satisfactory N
      Ac encapsulation efficiency (more than 67%) and a prolonged release (by 168 h)
      were achieved.

PMID- 29175646
TI  - Communication of genetic information to families with inherited rhythm disorders.
AB  - Given the dynamic nature of the electrical activity of the heart and ongoing
      challenges in the diagnostics of inherited heart rhythm disorders, genetic
      information can be a vital aspect of family management. Communication of genetic
      information is complex, and the responsibility to convey this information to the
      family lies with the proband. Current practice falls short, requiring additional
      support from the clinician and multidisciplinary team. Communication is a 2-part
      iterative process, reliant on both the understanding of the probands and their
      ability to effectively communicate with relatives. With the surge of high
      throughput genetic testing, results generated are increasingly complex, making
      the task of communication more challenging. Here we discuss 3 key issues. First,
      the probabilistic nature of genetic test results means uncertainty is inherent to
      the practice. Second, secondary findings may arise. Third, personal preferences,
      values, and family dynamics also come into play and must be acknowledged when
      considering how best to support effective communication. Here we provide insight
      into the challenges and provide practical advice for clinicians to support
      effective family communication. These strategies include acknowledging and
      managing genetic uncertainty, genetic counseling and informed consent, and
      consideration of personal and familial barriers to effective communication. We
      will explore the potential for developing resources to assist clinicians in
      providing patients with sufficient knowledge and support to communicate complex
      information to their at-risk relatives. Specialized multidisciplinary clinics
      remain the best equipped to manage patients and families with inherited heart
      rhythm disorders given the need for a high level of information and support.

PMID- 29175647
TI  - Gamma-glutamyl transferase and the risk of atherosclerosis and coronary heart
      disease.
AB  - Gamma-glutamyl transferase (GGT) is a ubiquitous cell surface enzyme that cleaves
      extracellular glutathione (G-SH) or other gamma-glutamyl compounds. GGT serves to
      increase the availability of amino acids, primarily cysteine, for intracellular G
      SH synthesis and plays a crucial role in maintaining G-SH homeostasis and defense
      against oxidative stress in organisms. Measurement of circulating GGT activity is
      widely used for the diagnosis of liver and obstructive biliary diseases and as an
      indicator of alcohol consumption. Epidemiological studies suggest an association
      between elevated GGT activity level and a risk of incident coronary heart disease
      (CHD) or CHD-related mortality. Elevated GGT activity level is associated with a
      plethora of cardio-metabolic risk factors, including traditional cardiovascular
      risk factors, metabolic syndrome, systemic inflammation, oxidative stress burden
      and various comorbidities that incur a negative impact on patient risk profile
      and prognosis. Experimental studies and studies of human atherosclerotic plaques
      have revealed not only the presence of catalytically active GGT in
      atherosclerotic plaques, but also a correlation between GGT activity and indices
      of plaque instability, suggesting direct involvement in the pathophysiology of
      atherosclerosis and related clinical events via promotion of pro-oxidant
      reactions by the enzyme. However, it remains unknown whether GGT plays a direct
      role in the pathophysiology of atherosclerosis and CHD or is merely a correlate
      of coexisting cardiovascular risk factors. The exact molecular mechanisms of GGT
      participation in atherosclerosis or CHD and assessment of GGT-lowering therapies,
      as well as their impact on clinical outcomes, remain to be investigated in
      longitudinal studies.

PMID- 29175648
TI  - Prognostic significance of neutrophil to lymphocyte ratio in patients with
      gastrointestinal stromal tumors: A meta-analysis.
AB  - BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is reported to be a
      prognostic factor in multiple malignancies. However, its prognostic value in
      patients with gastrointestinal stromal tumors (GISTs) remains controversial. This
      study aims to evaluate the prognostic value of preoperative NLR in GISTs.
      METHODS: MEDLINE, EMBASE, and, Cochrane databases were searched until February
      2017. Eligible articles were defined as studies assessing the prognostic role of
      preoperative NLR in GISTs. The end points were overall survival (OS), disease
      free survival (DFS), recurrence-free survival (RFS), and clinicopathological
      parameters. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence
      intervals (CIs) were calculated using fixed-effects/random-effects models.
      RESULTS: A total of eight studies comprising 1676 patients with GISTs were
      included. Elevated NLR had an association with decreased DFS/RFS (HR: 2.18, 95%
      CI: 1.30-3.67, P=0.003), but not OS (HR: 1.74, 95% CI: 0.63-4.84, P=0.29). The
      findings from most subgroup analyses were consistent with those from the overall
      analysis. Moreover, high NLR was significantly correlated with male, stomach
      lesion, tumor size (>5cm), tumor rupture (+), tumor recurrence (+), mitotic index
      (>5/50HPF), and NIH risk category (high/intermediate). CONCLUSIONS: Elevated
      preoperative NLR may be an unfavorable prognostic biomarker in patients with
      GISTs.

PMID- 29175649
TI  - Anti-Mullerian Hormone: genetic and environmental effects.
AB  - Anti-Mullerian hormone (AMH) is a homodimeric glycoprotein produced by granulosa
      cells of growing ovarian follicles. AMH appears to have an inhibitory effect on
      both primordial follicle recruitment and responsiveness of growing follicles to
      follicle-stimulating hormone (FSH). This hormone is considered to be a reliable
      marker of ovarian reserve; therefore, it is crucial to determine which factors
      influence AMH levels for prognostic and diagnostic purposes. In this review we
      intend to discuss the effect of genetic and environmental factors which may lead
      to AMH interindividual variability.

PMID- 29175650
TI  - The Asparagine-Rich Protein NRP Facilitates the Degradation of the PP6-type
      Phosphatase FyPP3 to Promote ABA Response in Arabidopsis.
AB  - The phytohormone abscisic acid (ABA) plays critical roles in abiotic stress
      responses and plant development. In germinating seeds, the phytochrome-associated
      protein phosphatase, FyPP3, negatively regulates ABA signaling by
      dephosphorylating the transcription factor ABI5. However, whether and how FyPP3
      is regulated at the posttranscriptional level remains unclear. Here, we report
      that an asparagine-rich protein, NRP, interacts with FyPP3 and tethers FyPP3 to
      SYP41/61-positive endosomes for subsequent degradation in the vacuole. Upon ABA
      treatment, the expression of NRP was induced and NRP-mediated FyPP3 turnover was
      accelerated. Consistently, ABA-induced FyPP3 turnover was abolished in an nrp
      null mutant. On the other hand, FyPP3 can dephosphorylate NRP in vitro, and
      overexpression of FyPP3 reduced the half-life of NRP in vivo. Genetic analyses
      showed that NRP has a positive role in ABA-mediated seed germination and gene
      expression, and that NRP is epistatic to FyPP3. Taken together, our results
      identify a new regulatory circuit in the ABA signaling network, which links the
      intracellular trafficking with ABA signaling.

PMID- 29175651
TI  - Subclinical cerebrovascular disease in NAFLD without overt risk factors for
      atherosclerosis.
AB  - BACKGROUND AND AIMS: Non-alcoholic fatty liver disease is recognized not only as
      part of the metabolic syndrome but also as an independent predictor of
      cardiovascular disease. METHODS: In this study, NMR spectroscopy method, together
      with perfusion techniques, was used to detect subclinical brain vascular damage
      in subjects with NAFLD without overt atherosclerosis risk factors (i.e.
      hypertension, diabetes, hypercholesterolemia, obesity). RESULTS: The results
      suggest that subjects with histologically proven NAFLD have a reduced cerebral
      perfusion (CBFr) confined to limited brain areas, i.e., left semioval center and
      posterior cingulate cortex. No statistically significant differences in CBFr
      values were found, dividing the NAFLD cohort into subgroups, considering NAS
      score, presence/absence of NASH/fibrosis, and degree of steatosis. CONCLUSIONS:
      Our data suggest that NAFLD per se may be involved in cerebral atherosclerotic
      disease. It will be interesting to draw longitudinal studies to determine whether
      these changes could evolve in more serious cerebral injury.

PMID- 29175652
TI  - Serum amyloid A3 is pro-atherogenic.
AB  - BACKGROUND AND AIMS: Serum amyloid A (SAA) predicts cardiovascular events.
      Overexpression of SAA increases atherosclerosis development; however, deficiency
      of two of the murine acute phase isoforms, SAA1.1 and SAA2.1, has no effect on
      atherosclerosis. SAA3 is a pseudogene in humans, but is an expressed acute phase
      isoform in mice. The goal of this study was to determine if SAA3 affects
      atherosclerosis in mice. METHODS: ApoE-/- mice were used as the model for all
      studies. SAA3 was overexpressed by an adeno-associated virus or suppressed using
      an anti-sense oligonucleotide approach. RESULTS: Over-expression of SAA3 led to a
      4-fold increase in atherosclerosis lesion area compared to control mice (p =
      0.01). Suppression of SAA3 decreased atherosclerosis in mice genetically
      deficient in SAA1.1 and SAA2.1 (p < 0.0001). CONCLUSIONS: SAA3 augments
      atherosclerosis in mice. Our results resolve a previous paradox in the literature
      and support extensive epidemiological data that SAA is pro-atherogenic.

PMID- 29175653
TI  - IgM antibodies against phosphorylcholine promote polarization of T regulatory
      cells from patients with atherosclerotic plaques, systemic lupus erythematosus
      and healthy donors.
AB  - BACKGROUND AND AIMS: IgM antibodies against phosphorylcholine (anti-PC) are
      negatively associated with atherosclerosis, cardiovascular disease (CVD) and
      systemic lupus erythematosus (SLE), where the risk of CVD and atherosclerosis is
      high. We here study the effects of IgM anti-PC immune regulation. METHODS:
      Mononuclear leukocytes were isolated from peripheral blood (PBMC) obtained from
      healthy blood donors, six SLE patients with age- and sex-matched controls, and
      symptom-giving human atherosclerotic plaques. The proportion of Th17 (CD4+CCR6+)
      and Treg (CD4+CD25+CD127dim/-) cells was determined by flow cytometry in CD4+T
      cells after 6 days of culture with Th17 or Treg-polarizing cytokines, with PMA
      and Ionomycin stimulation. IgM anti-PC were extracted from total IgM, with flow
      through IgM as controls. Dendritic cells (DC) were differentiated from PBMC.
      Antibody peptide/protein characterization was done by a proteomics de novo
      sequencing approach. RESULTS: IgM anti-PC increased significantly the proportion
      of Tregs from healthy donors, SLE patients and atherosclerotic plaque cells while
      control antibodies did not. T cells from SLE patients had a significantly lower
      proportion of Tregs and a higher proportion of Th17 cells as compared to matched
      controls. IgM anti-PC, but not control antibodies, significantly reduced the
      production of IL-17 and TNF-alpha in cell cultures from SLE patients and
      atherosclerotic plaque cells. IgM anti-PC interacted with CD40 and kept DCs in an
      immature stage, potentially being tolerogenic. We observed differences in the IgM
      peptide expression levels in anti-PC compared to control antibodies. CONCLUSIONS:
      IgM anti-PC promote polarization of Tregs, which could represent a novel
      protective mechanism in atherosclerosis and autoimmune conditions as SLE.

PMID- 29175654
TI  - Arterial inflammation measured by 18F-FDG-PET-CT to predict coronary events in
      older subjects.
AB  - BACKGROUND AND AIMS: Although 18F-fluorodeoxyglucose (FDG) uptake has emerged as
      a sensitive and reliable marker of atherosclerotic inflammation, its additive
      predictive value for future coronary disease in older subjects is unknown. The
      aim of this study was to test the prognostic value of aortic inflammation
      detected via FDG-positron emission tomography (PET)-computed tomography (CT) in
      older subjects. METHODS: We retrospectively utilized the records of 309 subjects
      aged over 65 years, without a history of coronary artery disease, who underwent
      18F-FDG-PET-CT mostly due to the clinical suspicion of cancer, but eventually
      turned out to be cancer-free. Target-to-background ratio (TBR) was calculated at
      the ascending aorta. The endpoint was occurrence of coronary heart disease (CHD)
      events. RESULTS: During a median follow-up of 3.9 years, 28 subjects experienced
      CHD events and 12 patients died due to non-CHD causes. The highest TBR tertile
      was associated with a high CHD event rate, accounting for death due to non-CHD
      causes as a competing risk (Gray test, p = 0.005). In a Fine and Gray competing
      risk proportional hazard regression model, TBR was associated with significantly
      high CHD events independently of FRS, with a hazard ratio (HR) of 1.19 per 0.1
      TBR increase (p < 0.001). Likewise, a significant increase in the area under the
      curve (from 0.57 to 0.73, p = 0.028) and a significant improvement in net
      reclassification (0.42, p = 0.038) were observed when TBR was added to the model
      with FRS alone. CONCLUSIONS: In older subjects with no history of malignant
      disease or overt coronary artery disease, arterial inflammation evaluated by FDG
      uptake provides information on future occurrence of coronary artery events.

PMID- 29175655
TI  - Thrombogenicity and central pulse pressure to enhance prediction of ischemic
      event occurrence in patients with established coronary artery disease: The MAGMA
      ischemia score.
AB  - BACKGROUND AND AIMS: Conventional cardiovascular risk estimators based on
      clinical demographics have limited prediction of coronary events. Markers for
      thrombogenicity and vascular function have not been explored in risk estimation
      of high-risk patients with coronary artery disease. We aimed to develop a
      clinical and biomarker score to predict 3-year adverse cardiovascular events.
      METHODS: Four hundred eleven patients, with ejection fraction >=40% undergoing
      coronary angiography, and found to have a luminal diameter stenosis >=50%, were
      included in the analysis. Thrombelastography indices and central pulse pressure
      (CPP) were determined at the time of catheterization. RESULTS: We identified
      predictors of death, myocardial infarction (MI) or stroke and developed a
      numerical ischemia risk score. The primary endpoint of cardiovascular death, MI
      or stroke occurred in 22 patients (5.4%). The factors associated with events were
      age, prior PCI or CABG, diabetes, CPP, and thrombin-induced platelet-fibrin clot
      strength, and were included in the MAGMA-ischemia score. The MAGMA-ischemia score
      showed a c-statistic of 0.85 (95% Confidence Interval [CI] 0.80-0.87; p<0.001)
      for the primary endpoint. In the subset of patients who underwent
      revascularization, the c-statistic was 0.90 (p<0.001). Patients with MAGMA
      ischemia score greater than 5 had highest risk to develop clinical events, hazard
      ratio for the primary endpoint: 13.9 (95% CI 5.8-33.1, p<0.001) and for the
      secondary endpoint: 4.8 (95% CI 2.3-9.6, p<0.001). When compared to previous
      models, the MAGMA-ischemia score yielded a higher discrimination. CONCLUSIONS:
      Inclusion of CPP and assessment of thrombogenicity in a novel score for patients
      with documented CAD enhanced the prediction of events.

PMID- 29175656
TI  - Pyranose ring puckering in aldopentoses, ketohexoses and deoxyaldohexoses. A
      molecular dynamics study.
AB  - Conformation of monosaccharides, including the ring shape, has for years been the
      subject of intensive research. Although d-aldohexopyranoses are the most
      extensively studied pyranoses, there also exist other groups of saccharides that
      contain analogous chemical system of the six-membered ring. Here we describe in
      details the results of the molecular dynamics-based conformational analysis
      concerning a series of pyranoses, namely: d-aldopentoses, d-ketohexoses as well
      as deoxy- (d-quinovose, l-fucose, l-rhamnose) and dideoxy- (abequose, paratose,
      tyvelose, digitoxose) derivatives of aldohexoses. By using the carbohydrate
      dedicated GROMOS 56a6CARBO force field, we determined the conformational
      properties of both the lactol and hydroxymethyl groups as well as the anomeric
      populations for all considered compounds. The orientation of the lactol group
      follows the trend expected on the basis of the exo-anomeric effect for all
      compounds whereas the conformation of the hydroxymethyl group in d-ketohexoses is
      represented by the two gauche (with respect to the ring oxygen atom) rotamers.
      The special emphasis is put on the ring-inversion properties studied in the
      context of both the full chair-chair inversion and the chair-boat/skew-boat
      rearrangement. The calculated ring-distortion energies, compared with those
      obtained for regular d-aldohexopyranoses allowed for estimating the influence of
      particular substituents on the ring flexibility. Overall, such influence is
      correlated with the dimension of the substituent and its orientation but is
      limited to the case of the chair-chair inversion whereas the chair-to-boat/skew
      boat rearrangement exhibits roughly the same properties for all pyranoses. For
      all d-aldopyranoses the alpha anomers exhibit lower ring-inversion free energies
      in comparison to the beta anomers whereas this trend is inverted in the case of d
      ketohexopyranoses.

PMID- 29175657
TI  - A combined variable temperature 600 MHz NMR/MD study of the calcium release agent
      cyclic adenosine diphosphate ribose (cADPR): Structure, conformational analysis,
      and thermodynamics of the conformational equilibria.
AB  - A combined variable temperature 600 MHz NMR/molecular dynamics study of the Ca2+
      release agent cyclic adenosine 5'-diphosphate ribose (cADPR) was conducted. In
      addition to elucidating the major and minor orientations of the conformationally
      flexible furanose rings, gamma- (C4'-C5'), and beta- (C5'-O5') bonds, the
      thermodynamics (DeltaHo, DeltaSo) associated with each of these conformational
      equilibria were determined. Both furanose rings were biased towards a south
      conformation (64-74%) and both beta-bonds heavily favored trans conformations.
      The R-ring gamma-bond was found to exist almost exclusively as the gamma+
      conformer, whereas the A-ring gamma-bond was a mixture of the gamma+ and gammat
      conformers, with the trans conformer being slightly favored. Enthalpic factors
      accounted for most of the observed conformational preferences, although the R
      ring furanose exists as its major conformation based solely on entropic factors.
      There was excellent agreement between the NMR and MD results, particularly with
      regard to the conformer identities, but the MD showed a bias towards gamma+
      conformers. The MD results showed that both N-glycosidic chi-bonds are
      exclusively syn. Collectively the data allowed for the construction of a model
      for cADPR in which many of the conformationally flexible units in fact
      effectively adopt single orientations and where most of the conformational
      diversity resides in its A-ring furanose and gamma-bond.

PMID- 29175658
TI  - Sonformational study of persulfated propyl glucuronide.
AB  - Glucuronic acid is an important constituting block of biologically active
      glycosaminoglycans where it can be present in non-sulfated, mono-sulfated and di
      sulfated forms. Despite that some investigators reported previously that the
      exhaustively sulfated glucuronic acid moiety was characterized with unusual 1H-1H
      coupling constants and some times chemical shifts, these were just qualitative
      studies in which their authors suggested that the mentioned deviations in NMR
      spectra might mean complete inversion of the normal D-pyranoside chair
      conformation 4C1 to 1C4. Herein we outline a detailed conformational
      investigation showing that the distortion in the pyranoside ring of the
      persulfated glucuronic acid cannot be described simply with 4C1<->1C4 inversion.
      Instead, the experimental NOE data clearly indicate that two skew-boat
      conformers, OS2 and 3S1, provide significant contribution to the conformational
      equilibrium.

PMID- 29175659
TI  - DIDMH in combination with triflic acid - A new promoter system for thioglycoside
      glycosyl donors.
AB  - We have explored the possibility of using 1,3-diiodo-5,5-dimethylhydantoin
      (DIDMH) as an alternative to N-iodosuccinimide (NIS) for activation of glycosyl
      donors of the thioglycoside type in various glycosylation reactions. DIDMH was
      found to match NIS when it comes to the capability to activate thioglycosides and
      provide glycosylation products in good yields. Notably, with the two equivalents
      of reactive iodonium ions per molecule of DIDMH less mass needs to be added
      making this activator a more atom economically alternative to NIS. Furthermore,
      DIDMH was found to be stable upon storage for weeks and comparably priced to NIS.
      With this knowledge in hand we therefore encourage the carbohydrate community to
      consider using DIDMH for activation of thioglycosides in glycosylation reactions.

PMID- 29175660
TI  - Chemo-enzymatic synthesis of the glucagon containing N-linked oligosaccharide and
      its characterization.
AB  - The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of
      glucagon, a peptide hormone that regulates the blood sugar level, is described.
      We synthesized the glycosylated glucagon by chemical synthesis of an N
      acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the
      transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis
      endo-beta-N-acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as
      a donor substrate. The sialo-oligosaccharide-attached glucagon synthesized showed
      high resistance against protease degradation and stimulated the release of
      glucose from mouse hepatocytes when added to cells. The synthetic glucagon showed
      slightly higher activity than native glucagon and has potential as a therapeutic
      agent for treating diabetic patients.

PMID- 29175661
TI  - Virtual journal club: an example of the growing importance of social media in
      pathology.

PMID- 29175662
TI  - Comorbidities in relation to fatality of first myocardial infarction.
AB  - INTRODUCTION: Present knowledge concerning potential associations between
      comorbidities and the fatality of a first myocardial infarction (MI) is limited.
      AIM: To identify comorbidities in 45-70-year-old individuals who suffered a first
      MI and died within 7 days in Stockholm County from 1992-1994. In addition, to
      assess how each of the comorbidities identified, as well as the number of
      hospitalizations during the 10-year period prior to the MI, was associated with
      MI fatality. METHODS: The data collected on our inception cohort of 1984 first
      MI, of which 524 were fatal within 7 days, were primarily self-reported, proxy
      reported by questionnaire and/or extracted from comprehensive national registers.
      Comorbidities among fatal cases with a prevalence >2% were identified. Risk
      ratios (with 95% confidence intervals) for the association of MI fatality with
      number of prior hospitalizations and specific comorbidities were calculated using
      binomial regression with log link. A structured review of autopsy reports on
      fatal cases was performed in order to identify additional indicators of
      comorbidities. RESULTS: After adjusting for sex, age and disposable income, the
      number of previous hospitalizations was associated with 7-day MI fatality. Of the
      comorbidities identified as prevalent in fatal cases, the following were
      associated with 7-day fatality in crude analysis: epilepsy, heart failure,
      stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases,
      diabetes, and rheumatoid arthritis. Indicators of comorbidities identified from
      autopsy data included a silent MI, severe atherosclerosis of the abdominal aorta,
      and hepatic steatosis. Adjustments for sex and age (although not possible for
      epilepsy and alcoholism), did not substantially alter results. CONCLUSIONS: Our
      current findings indicate that in connection with a first MI, particular
      attention should be paid to those with repeated prior hospitalizations and/or
      epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma,
      psychiatric diseases, diabetes and rheumatoid arthritis.

PMID- 29175663
TI  - Changes in neurofilament 200 and tyrosine hydroxylase expression in the cardiac
      innervation of diabetic rats during aging.
AB  - Changes in sensory and sympathetic innervation during diabetes mellitus (DM) can
      be a predictor of arrhythmias, silent myocardial ischemia, and chronic heart
      failure, but knowledge about these changes is still unsatisfactory. We analyzed
      whether prolonged DM induces changes in density of sensory and sympathetic nerve
      terminals of rat's heart and whether it contributes to cardiomyopathy during
      aging. DM was induced by i/p injecting 55 mg/kg streptozotocin to male Sprague
      Dawley rats, while a control group received a citrate buffer. DM in the rats was
      validated by measuring blood glucose level. Animals were sacrificed after 2
      weeks, 2 months, 6 months, and 12 months. Five areas of cardiac sections were
      analyzed. Antibodies raised against tyrosine hydroxylase (TH) and neurofilament
      200 kDa (NF 200) were used to detect sympathetic and sensory fibers. TH
      immunoreactive fiber density increased in DM groups 2 weeks after induction,
      reaching a peek after 2 months, while in the later stages of DM (6 and 12
      months), there was no significant difference compared to control. NF 200
      immunoreactive fiber density increased 2 weeks after induction compared to
      control. There was no consistent pattern of change during the given period in
      both the DM or control groups. In the DM group, we found thickening of the left
      ventricle wall (P<.05) as the sign of cardiomyopathy. Our findings suggest that
      hyperglycemia as a hallmark of DM in early stages can lead to proliferation of
      sympathetic and sensory nerve terminals. This finding can contribute to a better
      understanding of the occurrence of arrhythmias and silent myocardial ischemia in
      DM.

PMID- 29175664
TI  - Severe type B lactic acidosis and insulin-resistant hyperglycemia related to
      cadaveric kidney transplantation.

PMID- 29175665
TI  - Use of dexmedetomidine in a cardiac intensive care unit.

PMID- 29175666
TI  - Bilateral adductor canal block catheters in patients undergoing simultaneous
      bilateral knee arthroplasty: A series of 17 patients.

PMID- 29175667
TI  - Vitamin K1 inversely correlates with glycemia and insulin resistance in patients
      with type 2 diabetes (T2D) and positively regulates SIRT1/AMPK pathway of glucose
      metabolism in liver of T2D mice and hepatocytes cultured in high glucose.
AB  - There is no previous study in the literature that has examined the relationship
      between circulating vitamin K1 (VK1) with glycemic status in type 2 diabetes
      (T2D). Moreover, scientific explanation for the beneficial role of VK1
      supplementation in lowering glycemia in diabetes is yet to be determined. This
      study for the first time demonstrated that circulating VK1 was significantly
      lower in T2D patients compared to age-matched control subjects, and VK1 levels in
      T2D were significantly and inversely associated with fasting glucose and insulin
      resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], which
      suggest that boosting plasma VK1 may reduce the fasting glucose and insulin
      resistance in T2D patients. Using high-fat-diet-fed T2D animal model, this study
      further investigated the positive effect of VK1 supplementation on glucose
      metabolism and examined the underlying molecular mechanism. Results showed that
      VK1 supplementation [1, 3, 5 MUg/kg body weight (BW), 8 weeks] dose dependently
      improved the glucose tolerance; decreased BW gain, fasting glucose and insulin,
      glycated hemoglobin, HOMA-IR and cytokine secretion (monocyte chemoattractant
      protein-1 and interleukin-6); and regulated the signaling pathway of hepatic
      glucose metabolism [sirtuin 1 (SIRT1)/AMP-activated protein kinase
      (AMPK)/phosphoinositide 3-kinase/phosphatase and tensin homolog/glucose
      transporter 2/glucokinase/glucose 6 phosphatase], lipid oxidation (peroxisome
      proliferator-activated receptor alpha/carnitine palmitoyltransferase 1A) and
      inflammation (nuclear factor kappa B) in T2D mice. Comparative signal silencing
      studies also depicted the role of SIRT1/AMPK in mediating the effect of VK1 on
      glucose metabolism, lipid oxidation and inflammation in high-glucose-treated
      cultured hepatocytes. In conclusion, this study demonstrates that circulating VK1
      has a positive effect on lowering fasting glucose and insulin resistance in T2D
      via regulating SIRT1/AMPK signaling pathway.

PMID- 29175668
TI  - Grape seed procyanidin extract ameliorates lead-induced liver injury via miRNA153
      and AKT/GSK-3beta/Fyn-mediated Nrf2 activation.
AB  - Lead-induced hepatotoxicity is characterized by an extensive oxidative stress.
      Grape seed procyanidin extract (GSPE) possesses abundant biological activities.
      Herein, we investigated the protective role of GSPE against lead-induced liver
      injury and determined the potential molecular mechanisms. In vivo, rats were
      treated with/without lead acetate (PbAc) (0.05%, w/v) in the presence/absence of
      GSPE (200 mg/kg). In vitro, hepatocytes were pretreated with/without GSPE (100
      MUg/ml) in the presence/absence of PbAc (100 MUM). PbAc administration to rats
      resulted in anemia, liver dysfunction, lead accumulation in the bone and liver,
      oxidative stress, DNA damage and apoptosis. GSPE significantly attenuated these
      adverse effects, except lead accumulation in liver. GSPE also decreased the
      expression of miRNA153 and increased the translocation of nuclear factor
      erythroid 2-related factor 2 (Nrf2) and levels of its downstream protein, and
      protein kinase B (AKT) phosphorylation in PbAc-induced liver injury. In primary
      hepatocytes treated with PbAc, GSPE increased hepatocyte viability and decreased
      lactate dehydrogenase release and reactive oxygen species levels. Dietary GSPE
      attenuated PbAc-induced liver injury in rats via an integrated mechanism
      associated with the miRNA153 and AKT/glycogen synthase kinase 3 beta/Fyn-mediated
      Nrf2 activation.

PMID- 29175669
TI  - Euterpe oleracea Mart. (acai) seed extract associated with exercise training
      reduces hepatic steatosis in type 2 diabetic male rats.
AB  - Type 2 diabetes mellitus contributes to an increased risk of metabolic and
      morphological changes in key organs, such as the liver. We aimed to assess the
      effect of the acai seed extract (ASE) associated with exercise training on
      hepatic steatosis induced by high-fat (HF) diet plus streptozotocin (STZ) in
      rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5
      weeks, followed by a single low dose of STZ (35 mg/kg i.p.). Control and diabetic
      groups were subdivided into four groups that were fed with standard chow diet for
      4 weeks. Control (C) group was subdivided into Sedentary C, Training C, ASE
      Sedentary C and ASE Training C. Diabetic (D) group was subdivided into Sedentary
      D, Training D, ASE Sedentary D and ASE Training D. ASE (200 mg/kg/day) was
      administered by intragastric gavage, and the exercise training was performed on a
      treadmill (30 min/day; 5 days/week). Treatment with ASE associated with exercise
      training reduced the blood glucose (70.2%), total cholesterol (81.2%), aspartate
      aminotransferase (51.7%) and hepatic triglyceride levels (66.8%) and steatosis
      (72%) in ASE Training D group compared with the Sedentary D group. ASE associated
      with exercise training reduced the hepatic lipogenic proteins' expression (77.3%)
      and increased the antioxidant defense (63.1%), pAMPK expression (70.2%),
      cholesterol transporters (71.1%) and the pLKB1/LKB1 ratio (57.1%) in type 2
      diabetic rats. In conclusion, ASE treatment associated with exercise training
      protects against hepatic steatosis in diabetic rats by reducing hepatic
      lipogenesis and increasing antioxidant defense and cholesterol excretion.

PMID- 29175670
TI  - ApoE is a major determinant of hepatic bile acid homeostasis in mice.
AB  - Apolipoprotein E (ApoE) plays a central role in lipid transport and cholesterol
      metabolism, with surplus cholesterol being removed from the liver through bile
      acid (BA) synthesis. Furthermore, BAs are of critical importance in fat
      absorption by forming intestinal lipid-bile salt mixed micelles. To define ApoE's
      role in BA homeostasis, the metabolism of cholesterol and BA was investigated in
      liver tissue and gallbladder bile of ApoE-deficient mice given a chow or high
      cholesterol/high-fat diet (HCHF) diet for 6 months. When compared to wild-type
      mice, muricholic acid (MCA) and chenodeoxycholic acid (CDCA) increased
      approximately 15-, 82-, 22- and 38-fold, respectively, in hepatic tissue of ApoE
      deficient mice given a chow or HCHF diet. Moreover, ApoE-deficient mice on an
      HCHF diet increased the amounts of hepatic free cholesterol, MCA and CDCA by 61%,
      61% and 50% (P<.05). Conversely, total cholesterol and cholesterol esters were
      unchanged, and the bile acids taurohyodeoxycholic acid, taurodeoxycholic acid and
      hyodeoxycholic acid decreased to one third as compared to the chow diet (P<.05).
      Additionally, quantitative reverse-transcription polymerase chain reaction assays
      revealed induced expression of the bile acid receptor (Fxr) and associated
      transcription factors, i.e.Fxr, Lrh, Lxra and Srebp1c. Transcript expression of
      Cyp2a12, Cyp1b1, Cyp2e1, Cyp3a16 and Cyp4a10 was also induced. Note that Cyp4a10
      catalyzes omega-hydroxylation of arachidonic acid to epoxy- and
      hydroxyeicosatrienoic acids to control vascular tone. Altogether, MCA and CDCA
      synthesis is selectively induced in ApoE-deficient mice. These hydrophilic BAs
      alter micellar size and structure to lower intestinal cholesterol solubilization.
      Furthermore, CDCA and MCA are potent FXR agonist and antagonist, respectively,
      and function in a regulatory loop to mitigate impaired ApoE function.

PMID- 29175672
TI  - Effect of minimally-invasive implantation of unicompartmental knee arthroplasty
      on cement penetration and biomechanical stability. An experimental study in human
      tibiae.

PMID- 29175671
TI  - Dietary omega-3 and omega-6 polyunsaturated fatty acids modulate hepatic
      pathology.
AB  - Recent evidence has suggested that dietary polyunsaturated fatty acids (PUFAs)
      modulate inflammation; however, few studies have focused on the pathobiology of
      PUFA using isocaloric and isolipidic diets and it is unclear if the associated
      pathologies are due to dietary PUFA composition, lipid metabolism or obesity, as
      most studies compare diets fed ad libitum. Our studies used isocaloric and
      isolipidic liquid diets (35% of calories from fat), with differing compositions
      of omega (omega)-6 or long chain (Lc) omega-3 PUFA that were pair-fed and
      assessed hepatic pathology, inflammation and lipid metabolism. Consistent with an
      isocaloric, pair-fed model we observed no significant difference in diet
      consumption between the groups. In contrast, the body and liver weight, total
      lipid level and abdominal fat deposits were significantly higher in mice fed an
      omega-6 diet. An analysis of the fatty acid profile in plasma and liver showed
      that mice on the omega-6 diet had significantly more arachidonic acid (AA) in the
      plasma and liver, whereas, in these mice omega-3 fatty acids such as
      eicosapentaenoic acid (EPA) were not detected and docosahexaenoic acid (DHA) was
      significantly lower. Histopathologic analyses documented that mice on the omega-6
      diet had a significant increase in macrovesicular steatosis, extramedullary
      myelopoiesis (EMM), apoptotic hepatocytes and decreased glycogen storage in
      lobular hepatocytes, and hepatocyte proliferation relative to mice fed the Lc
      omega-3 diet. Together, these results support PUFA dietary regulation of hepatic
      pathology and inflammation with implications for enteral feeding regulation of
      steatosis and other hepatic lesions.

PMID- 29175673
TI  - Astrocytic gamma-aminobutyric acid (GABA) transporters mediate guanidinoacetate
      transport in rat brain.
AB  - Guanidinoacetate (GAA) is a biosynthetic precursor of creatine, which plays a
      critical role in homeostasis of high-energy phosphates in the brain, but cerebral
      accumulation of GAA leads to neurological complications, such as epilepsy and
      seizures. The purpose of the present study was to clarify the contribution of the
      gamma-aminobutyric acid (GABA) transport systems to GAA transport in astrocytes
      by means of uptake studies in rat brain slices, primary astrocyte cultures and
      Chinese hamster ovary (CHO) cells expressing human GABA transporters (GATs). GAA
      uptake by rat brain slices was Na+- and Cl--dependent, and GABA-sensitive. The
      inhibitory effect of GABA, a common substrate of GATs, on GAA uptake by the brain
      slices was similar to that of beta-alanine, a selective substrate of
      GAT2/Slc6a13, GAT3/Slc6a11, and taurine transporter (TauT)/Slc6a6. Taurine, a
      high-affinity substrate of TauT/Slc6a6, exhibited a lesser inhibitory effect. In
      contrast, betaine, a substrate of betaine-GABA transporter 1 (BGT1)/Slc6a12, and
      creatine, a substrate of creatine transporter (CRT)/Slc6a8, had little inhibitory
      effect. A similar inhibition profile was observed in primary-cultured astrocytes.
      CHO cells expressing human GAT2/SLC6A13, GAT3/SLC6A11 and BGT1/SLC6A12 exhibited
      GAA transport, whereas CHO cells expressing GAT1/SLC6A1 did not. The Michaelis
      Menten values in CHO cells expressing GAT2/SLC6A13 and GAT3/SLC6A11 were similar
      to those in primary-cultured astrocytes. Overall, our results suggest that
      astrocytic GAT2/Slc6a13 and GAT3/Slc6a11 play major roles in GAA uptake as
      regulatory mechanisms of GAA in rat brain, while TauT/Slc6a6, BGT1/Slc6a12, and
      CRT/Slc6a8 make relatively small contributions.

PMID- 29175674
TI  - Deleterious effects of prenatal exposure to morphine on the spatial learning and
      hippocampal BDNF and long-term potentiation in juvenile rats: Beneficial
      influences of postnatal treadmill exercise and enriched environment.
AB  - Prenatal morphine exposure causes a variety of neurobehavioral alterations
      observed in later life. The present study investigated the effects of postnatal
      exercise and enriched environment (EE) on alterations in water maze learning and
      hippocampal long-term potentiation (LTP) and brain derived neurotrophic factor
      (BDNF) levels induced by exposure to morphine during prenatal period in rats. On
      gestation days 11-18, pregnant rats were injected twice daily with saline or
      morphine. Offspring were subjected to postnatal exercise and EE for 30 days and
      afterward, spatial learning and hippocampal LTP and BDNF levels were
      investigated. Prenatal morphine-exposure impaired the spatial learning and
      hippocampal LTP in both male and female offspring. Interestingly, postnatal
      exercise and EE increased performance in the water maze and improved LTP in both
      prenatally saline and morphine-exposed male and female rats. Prenatal morphine
      exposure also caused a reduction in the hippocampal BDNF levels in the female,
      but not male rats, and postnatal exercise and EE alleviated this deficit. Our
      results demonstrate that postnatal exercise and EE can improve deficits in water
      maze learning and hippocampal LTP and BDNF levels caused by prenatal morphine
      exposure.

PMID- 29175675
TI  - Recent developments in anti-Trichomonas research: An update review.
AB  - Trichomonas vaginalis is a major non-viral sexually-transmitted infection
      resulted into serious obstetrical and gynecological troubles. The increasing
      resistance to nitroimidazole therapy and recurrence makes it crucial to develop
      new drugs against trichomoniasis. Over the past few years, a large number of
      research articles highlighting the synthetic and natural product research to
      combat Trichomonas vaginalis have been published. Electronic databases were
      searched to collect all data from the year 2006 through June 2017 for anti
      Trichomonas activity potential of synthetic and natural products. This review
      article put together the synthetic and natural product research to find out an
      effective metronidazole alternative to cure trichomoniasis.

PMID- 29175676
TI  - Meta-analysis of the efficacy of modafinil versus placebo in the treatment of
      multiple sclerosis fatigue.
AB  - BACKGROUND: Clinical trials examining the therapeutic benefit of modafinil in MS
      fatigue provide conflicting data. The goal of this study was to systematically
      evaluate the efficacy of modafinil using a meta-analytic method. METHODS: A
      systematic literature search was performed on published peer reviewed articles
      from 2000 to 2017 using the Cochrane Library, PubMed, and EMBASE. This review
      included double blind, randomized controlled trials, which evaluated modafinil in
      MS fatigue. The primary outcome measure was the estimated treatment difference in
      the Modified Fatigue Impact Scale score (MFIS) and Fatigue Severity Scale score
      (FSS). A secondary outcome measure was the estimated treatment difference in the
      Symbol Digit Modalities Test (SDMT). RESULTS: A total of 303 patients from five
      randomized controlled trials were included in the analyses. Modafinil was
      superior to placebo with an estimated treatment difference according to the MFIS
      (MD = -5.27, 95% CI: -8.51 to -2.03, P = 0.001). For the FSS, there was no
      significant difference between the two groups (MD = 2.50, 95%CI: -0.70 to 5.70, P
      = 0.13). For the secondary outcome, there was no significant difference between
      groups studied using the SDMT (MD = 0.23, 95% CI: -0.25 to 0.71, P = 0.35).
      CONCLUSIONS: Our meta-analysis showed that modafinil was an effective
      pharmacologic therapy for MS fatigue. Additional research is required to
      determine optimal dosing and treatment schedules.

PMID- 29175677
TI  - Efficacy and safety of regorafenib in the treatment of metastatic colorectal
      cancer: A systematic review.
AB  - PURPOSE: Despite advances in the treatment of colorectal cancer, third-line
      treatment options are still limited. Regorafenib was approved in 2012 for the
      treatment of patients with metastatic colorectal cancer previously treated with
      approved standard therapy. The purpose of this review is to present existing
      clinical data on regorafenib. METHOD: We systematically searched the PubMed and
      Embase databases, as well as ASCO and ESMO conference abstracts, for studies in
      English including >=30 patients, evaluating the efficacy and safety of
      regorafenib in patients with metastatic colorectal cancer. A meta-analysis was
      conducted on the published, randomized phase III trials. RESULTS: 24 eligible
      studies were included. In two phase III trials, regorafenib significantly
      increased overall survival (OS), progression free survival (PFS), and disease
      control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months
      were presented. The meta-analysis indicated a significant greater treatment
      effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to
      placebo. The non-randomized studies mostly supported these results. The most
      frequently reported adverse events were hand-foot-skin reaction (25%-86%),
      hypertension (11%-47%) and fatigue (2%-73%). CONCLUSION: Large phase III
      randomized trials indicate that regorafenib provides a benefit in OS and PFS when
      compared to placebo. Adverse events were common, but manageable and typical of
      multi-target tyrosine kinase inhibitors. Further research is needed to
      investigate alternative approaches to the dosing of regorafenib and to explore
      clinical and molecular biomarkers that can guide patient selection.

PMID- 29175678
TI  - Systematic review of the clinical and economic value of gene expression profiles
      for invasive early breast cancer available in Europe.
AB  - Gene expression profiles with prognostic capacities have shown good performance
      in multiple clinical trials. However, with multiple assays available and numerous
      types of validation studies performed, the added value for daily clinical
      practice is still unclear. In Europe, the MammaPrint, OncotypeDX, PAM50/Prosigna
      and Endopredict assays are commercially available. In this systematic review, we
      aim to assess these assays on four important criteria: Assay development and
      methodology, clinical validation, clinical utility and economic value. We
      performed a literature search covering PubMed, Embase, Web of Science and
      Cochrane, for studies related to one or more of the four selected assays. We
      identified 147 papers for inclusion in this review. MammaPrint and OncotypeDX
      both have evidence available, including level IA clinical trial results for both
      assays. Both assays provide prognostic information. Predictive value has only
      been shown for OncotypeDX. In the clinical utility studies, a higher reduction in
      chemotherapy was achieved by OncotypeDX, although the number of available studies
      differ considerably between tests. On average, economic evaluations estimate that
      genomic testing results in a moderate increase in total costs, but that these
      costs are acceptable in relation to the expected improved patient outcome.
      PAM50/prosigna and EndoPredict showed comparable prognostic capacities, but with
      less economical and clinical utility studies. Furthermore, for these assays no
      level IA trial data are available yet. In summary, all assays have shown
      excellent prognostic capacities. The differences in the quantity and quality of
      evidence are discussed. Future studies shall focus on the selection of
      appropriate subgroups for testing and long-term outcome of validation trials, in
      order to determine the place of these assays in daily clinical practice.

PMID- 29175680
TI  - Inductive reasoning and doubt in obsessive compulsive disorder.
AB  - BACKGROUND AND OBJECTIVES: Previous studies show that individuals with obsessive
      compulsive disorder (OCD) accord more importance than healthy controls (HC) to
      alternative conclusions, resulting in increased doubt regarding an initial
      conclusion. The goal of the present study was to replicate and extend this
      finding. METHODS: Eighteen participants diagnosed with OCD and 16 HC completed
      the Reasoning with Inductive Arguments Task (RIAT), which operationalizes doubt
      as change in confidence towards a conclusion after alternative conclusions are
      presented. To examine conditions that facilitate doubt, the impact of alternative
      conclusions that both supported and contradicted the initial conclusion was
      compared, as well as the effect of neutral and OCD-relevant item content.
      RESULTS: Both the OCD and HC groups decreased confidence after contradicting
      conclusions, but only the HC group increased confidence when presented with
      supporting conclusions. Furthermore, decrease in confidence in the OCD group
      correlated with OCD symptom severity. LIMITS: The RIAT could be adapted to better
      take into account of OCD subtypes. CONCLUSION: Doubt generation may contribute to
      obsessional doubting.

PMID- 29175679
TI  - Monitoring microbial communities using light sheet fluorescence microscopy.
AB  - Microbes often live in dense, dynamic, multi-species communities whose
      architecture and function are intimately intertwined. Imaging these complex,
      three-dimensional ensembles presents considerable technical challenges, however.
      In this review, I describe light sheet fluorescence microscopy, a technique that
      enables rapid acquisition of three-dimensional images over large fields of view
      and over long durations, and I highlight recent applications of this method to
      microbial systems that include artificial closed ecosystems, bacterial biofilms,
      and gut microbiota. I comment also on the history of light sheet imaging and the
      many variants of the method. Light sheet techniques have tremendous potential for
      illuminating the workings of microbial communities, a potential that is just
      beginning to be realized.

PMID- 29175681
TI  - In vitro inoculation of Aeromonas hydrophila and Pseudomonas fluorescens in
      cryopreserved silver barb (Barbodes gonionotus) milt: Effect on fertilization
      capacity and transmission potential to embryos.
AB  - Purposive use of cryopreserved sperm contaminated with pathogenic agents has
      increased the risk of spreading of fish diseases. The objective of this study was
      to investigate the effects of A. hydrophila subsp. hydrophila and P. fluorescens
      inoculations into cryostored milt on fertilization capacity and transmission
      potential to embryos of silver barb (Barbodes gonionotus) with or without 0.25%
      penicillin-streptomycin (PS) administration. The experiment comprised six
      treatments: addition of milt into T1) extender only, T2) extender with 0.25% PS,
      T3) extender with A. hydrophila subsp. hydrophila (BG19), T4) extender with A.
      hydrophila subsp. hydrophila (BG19) and 0.25% PS, T5) extender with P.
      fluorescens (BG20) and T6) extender with P. fluorescens (BG20) and 0.25% PS. Milt
      were loaded into 0.25-mL straws and cryostored in the controlled-rate
      programmable freezer. After a cryostorage for 28 d, post-thawed sperm were
      evaluated for the fertilization capacity and risk of pathogen transmission to
      embryos. Inoculation of A. hydrophila subsp. hydrophila and P. fluorescens into
      extended milt (T3 and T5) caused a reduction (P < 0.05) in fertilization capacity
      of cryopreserved sperm. Cryopreserved sperm inoculated with the two pathogenic
      bacteria and 0.25% PS (T4 and T6) did not fertilize the eggs. The two pathogenic
      bacteria could be transmitted into embryos after artificial insemination of eggs
      with bacterial-inoculated cryopreserved sperm, suggesting that the risks of
      disease transmission via cryopreserved fish sperm would exist. This is the first
      study reporting pathogenic bacterial transmission on in vitro fish embryos
      through artificial insemination of cryopreserved sperm.

PMID- 29175682
TI  - Expression of progesterone receptor protein in the ovine uterus during the
      estrous cycle: Effects of nutrition, arginine and FSH.
AB  - To evaluate expression of progesterone receptor (PGR) AB in follicle stimulating
      hormone (FSH)-treated or non-treated sheep administered with arginine (Arg) or
      saline (Sal) fed a control (C), excess (O) or restricted (U) diet, uterine
      tissues were collected at the early, mid and/or late luteal phases. In exp. 1,
      ewes from each diet were randomly assigned to one of two treatments, Arg or Sal
      administration three times daily from day 0 of the first estrous cycle until
      uterine tissue collection. In exp. 2, ewes were injected twice daily with FSH on
      days 13-15 of the first estrous cycle. Uterine tissues were immunostained to
      detect PGR followed by image analysis. PGR were detected in luminal epithelium
      (LE), endometrial glands (EG), endometrial stroma (ES), myometrium (Myo), and
      endometrial and myometrial blood vessels. The percentage of PR-positive cells
      and/or intensity of staining were affected by phase of the estrous cycle, plane
      of nutrition, and/or FSH but not by Arg. In exp. 1, percentage of PGR-positive
      cells in LE and EG but not in ES and Myo was greater at the early and mid than
      late luteal phase, was not affected by plane of nutrition, and was similar in LE
      and EG. Intensity of staining was affected by phase of the estrous cycle and
      plane of nutrition in LE, EG and Myo, and was the greatest in LE, less in EG, and
      least in ES and Myo. In exp. 2, percentage of PGR-positive cells in LE, EG, ES
      and Myo was affected by phase of the estrous cycle, but not by plane of
      nutrition; was greater at the early than mid luteal phase; and was greatest in LE
      and EG, less in luminal (superficial) ES and Myo and least in deep ES. Intensity
      of staining was affected by phase of the estrous cycle and plane of nutrition in
      all compartments but ES, and was the greatest in LE and luminal EG, less in deep
      EG, and least in ES and Myo. Comparison of data for FSH (superovulated) and Sal
      treated (non-superovulated) ewes demonstrated that FSH affected PR expression in
      all evaluated uterine compartments depending on plane of nutrition and phase of
      the estrous cycle. Thus, PGR are differentially distributed in uterine
      compartments, and PGR expression is affected by nutritional plane and FSH, but
      not Arg depending on phase of the estrous cycle. Such changes in dynamics of PGR
      expression indicate that diet plays a regulatory role and that FSH-treatment may
      alter uterine functions.

PMID- 29175683
TI  - PET microplastics do not negatively affect the survival, development, metabolism
      and feeding activity of the freshwater invertebrate Gammarus pulex.
AB  - Over the past decade, microscopic plastic debris, known as microplastics, emerged
      as a contaminant of concern in marine and freshwater ecosystems. Although
      regularly detected in aquatic environments, the toxicity of those synthetic
      particles is not well understood. To address this, we investigated whether the
      exposure to microplastics adversely affects the amphipod Gammarus pulex, a key
      freshwater invertebrate. Juvenile (6-9 mm) and adult (12-17 mm) individuals were
      exposed to irregular, fluorescent polyethylene terephthalate fragments (PET, 10
      150 MUm; 0.8-4,000 particles mL-1) for 24 h. Results show that body burden after
      24 h depends on the dose and age of G. pulex with juveniles ingesting more
      microplastics than adults. After chronic exposure over 48 d, microplastics did
      not significantly affect survival, development (molting), metabolism (glycogen,
      lipid storage) and feeding activity of G. pulex. This demonstrates that even high
      concentrations of PET particles did not negatively interfere with the analyzed
      endpoints. These results contradict previous research on marine crustaceans.
      Differences may result from variations in the exposure regimes (e.g., duration,
      particle concentrations), plastic characteristics (e.g., type, size, shape,
      additives) as well as the species-specific morphological, physiological and
      behavioral traits. As a detritivorous shredder G. pulex is adapted to feed on non
      digestible materials and might, therefore, be less sensitive towards exposure to
      synthetic particles. Accordingly, we argue that the autecology needs to be taken
      into account and that research should focus on identifying traits that render
      species susceptible to microplastic exposure.

PMID- 29175684
TI  - Removal of pharmaceutical compounds in water and wastewater using fungal
      oxidoreductase enzymes.
AB  - Due to recalcitrance of some pharmaceutically active compounds (PhACs),
      conventional wastewater treatment is not able to remove them effectively.
      Therefore, their occurrence in surface water and potential environmental impact
      has raised serious global concern. Biological transformation of these
      contaminants using white-rot fungi (WRF) and their oxidoreductase enzymes has
      been proposed as a low cost and environmentally friendly solution for water
      treatment. The removal performance of PhACs by a fungal culture is dependent on
      several factors, such as fungal species, the secreted enzymes, molecular
      structure of target compounds, culture medium composition, etc. In recent 20
      years, numerous researchers tried to elucidate the removal mechanisms and the
      effects of important operational parameters such as temperature and pH on the
      enzymatic treatment of PhACs. This review summarizes and analyzes the studies
      performed on PhACs removal from spiked pure water and real wastewaters using
      oxidoreductase enzymes and the data related to degradation efficiencies of the
      most studied compounds. The review also offers an insight into enzymes
      immobilization, fungal reactors, mediators, degradation mechanisms and
      transformation products (TPs) of PhACs. In brief, higher hydrophobicity and
      having electron-donating groups, such as amine and hydroxyl in molecular
      structure leads to more effective degradation of PhACs by fungal cultures. For
      recalcitrant compounds, using redox mediators, such as syringaldehyde increases
      the degradation efficiency, however they may cause toxicity in the effluent and
      deactivate the enzyme. Immobilization of enzymes on supports can enhance the
      performance of enzyme in terms of reusability and stability. However, the
      immobilization strategy should be carefully selected to reduce the cost and
      enable regeneration. Still, further studies are needed to elucidate the
      mechanisms involved in enzymatic degradation and the toxicity levels of TPs and
      also to optimize the whole treatment strategy to have economical and technical
      competitiveness.

PMID- 29175685
TI  - Does maternal environmental tobacco smoke interact with social-demographics and
      environmental factors on congenital heart defects?
AB  - Congenital heart defects (CHDs) are a major cause of death in infancy and
      childhood. Major risk factors for most CHDs, particularly those resulting from
      the combination of environmental exposures with social determinants and
      behaviors, are still unknown. This study evaluated the main effect of maternal
      environmental tobacco smoke (ETS), and its interaction with social-demographics
      and environmental factors on CHDs in China. A population-based, matched case
      control study of 9452 live-born infants and stillborn fetuses was conducted using
      the Guangdong Registry of Congenital Heart Disease data (2004-2014). The CHDs
      were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by
      cardia tomography/catheterization. Controls were randomly chosen from singleton
      newborns without any malformation, born in the same hospital as the cases and 1:1
      matched by infant sex, time of conception, and parental residence (same city and
      town to ensure sufficient geographical distribution for analyses). Face-to-face
      interviews were conducted to collect information on demographics, behavior
      patterns, maternal disease/medication, and environmental exposures. Conditional
      logistic regression was used to estimate odds ratios and 95% confidence intervals
      of ETS exposure on CHDs while controlling for all risk factors. Interactive
      effects were evaluated using a multivariate delta method for maternal
      demographics, behavior, and environmental exposures on the ETS-CHD relationship.
      Mothers exposed to ETS during the first trimester of pregnancy were more likely
      to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25-1.66).
      We also observed a significant dose-response relationship when mothers were
      exposed to ETS and an increasing number of risk factors and CHDs. There were
      greater than additive interactions for maternal ETS and migrant status, low
      household income and paternal alcohol consumption on CHDs. Maternal low education
      also modified the ETS-CHD association on the multiplicative scale. These findings
      may help to identify high-risk populations for CHD, providing an opportunity for
      targeted preventive interventions.

PMID- 29175686
TI  - Nest-defense behaviors in fathead minnows after lifecycle exposure to the
      antidepressant venlafaxine.
AB  - Venlafaxine is an antidepressant and anti-anxiety drug that has been detected in
      municipal wastewater at low MUg/L concentrations. In this study, the nest-defense
      behavior of adult male fathead minnows (Pimephales promelas) was observed in fish
      exposed for a full lifecycle to venlafaxine nominal concentrations of 0.88, 8.8,
      and 88 MUg/L (i.e. 1, 9.3, 75 MUg/L mean measured concentrations). Nest-defense
      behaviors quantified were the time taken to contact a dummy intruder fish (on a
      flexible stick, held near each nest) and the number of contacts made during a 1
      min period. In male fathead minnows exposed to venlafaxine over a full lifecycle
      at environmentally relevant nominal concentrations (i.e. 0.88 and 8.8 MUg/L) no
      significant effects were observed in behavior. However, in males exposed over a
      full lifecycle to the highest concentration of venlafaxine (i.e. 88 MUg/L), nest
      defense behaviors were increased in males with empty nests, as shown by the
      significantly elevated percentage of empty-nest males that made contact with the
      dummy intruder fish (89%) relative to the lower percentage of contacts (65%)
      among the Control males (p = 0.046). Lifecycle exposure to high venlafaxine (88
      MUg/L) caused males to over-protect their empty nests. Environmental venlafaxine
      concentrations are approximately 70 x lower than this, so it is unlikely that
      behavioral changes from venlafaxine exposure would occur in the environment.
      Normal nest defense behaviours in control males varied, depending on whether they
      were protecting empty nests or nests with eggs. Compared to Control males with
      empty nests, more Control males with eggs in their nests made contact with the
      dummy intruder fish (p = 0.014), contact was faster (i.e. <10 s, p = 0.011), and
      they hit the dummy intruder fish more times in 1 min (p = 0.031) This study is
      the first to assess reproductive behaviors in fish exposed to an antidepressant
      over a full lifecycle.

PMID- 29175687
TI  - Biouptake, toxicity and biotransformation of triclosan in diatom Cyclotella sp.
      and the influence of humic acid.
AB  - Triclosan is one of the most frequently detected emerging contaminants in aquatic
      environment. In this study, we investigated the biouptake, toxicity and
      biotransformation of triclosan in freshwater algae Cyclotella sp. The influence
      of humic acid, as a representative of dissolved organic matter, was also
      explored. Results from this study showed that triclosan was toxic to Cyclotella
      sp. with 72 h EC50 of 324.9 MUg L-1. Humic acid significantly reduced the
      toxicity and accumulation of triclosan in Cyclotella sp. SEM analysis showed that
      Cyclotella sp. were enormously damaged under 1 mg L-1 triclosan exposure and
      repaired after the addition of 20 mg L-1 humic acid. Triclosan can be
      significantly taken up by Cyclotella sp. The toxicity of triclosan is related to
      bioaccumulated triclosan as the algal cell numbers decreased when intracellular
      triclosan increased. A total of 11 metabolites were identified in diatom cells
      and degradation pathways are proposed. Hydroxylation, methylation,
      dechlorination, amino acids conjunction and glucuronidation contributed to the
      transformative reactions of triclosan in Cyclotella sp., producing biologically
      active products (e.g., methyl triclosan) and conjugation products (e.g.,
      glucuronide or oxaloacetic acid conjugated triclosan), which may be included in
      the detoxification mechanism of triclosan.

PMID- 29175688
TI  - Language-specific skills in intercultural healthcare communication: Comparing
      perceived preparedness and skills in nurses' first and second languages.
AB  - BACKGROUND: Interactions between people from different cultures are becoming
      increasingly commonplace in contemporary healthcare settings. To date, most
      research evaluating cross-cultural preparedness has assumed that medical
      professionals are speaking their first language (L1). However, as healthcare
      workers are increasingly mobile and patient populations are increasingly diverse,
      more and more interactions are likely to occur in a professional's non-native
      language (L2). OBJECTIVES: This study assessed and compared nurses' perceived
      cross-cultural preparedness and skillfulness in their interactions with patients
      from other cultures when speaking both their L1 and L2. The goal of this project
      was to inform the creation of a communication skills training program. DESIGN:
      Nurses reported their perceived cross-cultural preparedness and skillfulness
      (scales adapted from Park et al., 2009) in their L1 and L2 via an online
      questionnaire. SETTINGS: This questionnaire was distributed among nurses working
      in Vienna, Austria, through the Vienna Hospital Association (VHA). PARTICIPANTS:
      Nurses and nurses-in-training working in VHA hospitals participated. Most
      participants who provided demographic information were currently nurses (n=179)
      with an average of 16.88years (SD=11.50) of professional experience (range: 0
      40); n=40 were nurses-in-training with an average of 2.13years (SD=0.88) of
      experience (range: 1-5). METHODS: Descriptive statistics for each cross-cultural
      preparedness and skillfulness (in each language) are reported; comparisons
      between L1 and L2 responses were also conducted. Multiple regression analyses
      were used to identify predictors of preparedness and L1/L2 skillfulness. RESULTS:
      Nurses reported feeling significantly less confident in their skills when working
      in an L2, across a range of culture-related issues. Having had previous
      communication skills training predicted (better) self-reported L2 skillfulness,
      although it did not predict L1 skillfulness. CONCLUSIONS: These results indicate
      that there is a language-specific component to cross-cultural skillfulness. Thus,
      there is a need for language-specific skills training to address L2 skill
      deficits.

PMID- 29175689
TI  - Reflective seminaries grounded in caring science and lifeworld theory - A
      phenomenological study from the perspective of nursing students.

PMID- 29175690
TI  - Human trafficking education for nurse practitioners: Integration into standard
      curriculum.
AB  - BACKGROUND: Human trafficking is a crime resulting in serious negative health
      outcomes for the victims. To provide optimal care, thus improving health
      outcomes, healthcare providers must be able to identify victims as they seek care
      for acute and chronic physical illness, communicable diseases, sexually
      transmitted infections, and mental health disorders (Lederer and Wetzel, 2014;
      Oram et al., 2012). Unfortunately, healthcare providers lack appropriate
      knowledge of clues that would lead to victim identification. This may result in a
      failure to identify victims (Beck et al., 2015; Ross et al., 2015;
      Konstantopoulos et al., 2013; Chisolm-Straker et al., 2012). Increasing the
      number of healthcare providers able to identify, treat, and refer victims of
      trafficking for further care is imperative. OBJECTIVES: The study evaluated the
      knowledge level of student nurse practitioners enrolled in an adult, family, or
      pediatric clinical course. Knowledge domains included the definitions, laws,
      prevalence, identification, treatment, and community and social service
      resources. DESIGN/SETTING/PARTICIPANTS: The study was designed as a non
      probability sampling of adult, family, and pediatric nurse practitioner students
      (n=73). Participants included students enrolled in the Adult & Older Adult I or
      the Primary Care of the Child & Adolescent I course at a large public university.
      METHODS: The study was designed as a one hour educational intervention intended
      for presentation in a lecture-style format. The educational intervention included
      a PowerPoint lecture and embedded videos. The pre-survey, designed as a paper
      survey, contained a demographic section followed by six survey questions covering
      the six domains of interest. Following the intervention, participants completed
      the post-survey prior to leaving the classroom. RESULTS: Pre-survey results
      pinpointed knowledge gaps across all six domains under investigation. Post-survey
      results revealed an increase in knowledge across all six domains of interest.
      CONCLUSIONS: The educational intervention increased knowledge of human
      trafficking among students enrolled in a nurse practitioner program. Informed
      nurse practitioners have the ability to identify, treat, and refer victims of
      trafficking. As an integral part of the health care team, nurse practitioners
      should receive trafficking education as part of the standard course curricula.

PMID- 29175691
TI  - A theory of planned behaviour perspective on practitioners' beliefs toward the
      integration of the WIXX communication campaign messages and activities into daily
      practice.
AB  - OBJECTIVES: To favour the dissemination and the implementation of the WIXX
      multimedia communication campaign, the aim of this study was to examine
      practitioners' beliefs towards the integration of the WIXX campaign activities
      into daily practice. STUDY DESIGN: An exploratory qualitative study. METHODS:
      Overall, 58 community-based practitioners completed an online questionnaire based
      on the theory of planned behaviour guidelines pertaining to perceived
      advantages/disadvantages and perceived barriers/facilitators toward the campaign.
      A content analysis was performed by two independent coders to extract modal
      beliefs. Results were validated by a third coder. RESULTS: Local partners had a
      positive attitude toward the WIXX campaign, but significant barriers remained and
      needed to be addressed to ensure full implementation of this campaign (e.g. lack
      of time or resources, additional workload, complexity of the registration process
      and so forth). Beliefs were fragmented and diversified, indicating that they were
      highly context dependent. CONCLUSIONS: To conclude, some remaining challenges
      regarding the full implementation of the WIXX communication campaign were
      identified, suggesting that additional efforts might be needed to ensure the full
      adoption of the campaign by local practitioners.

PMID- 29175692
TI  - Interpreting microbiologically assisted cracking with Ee-pH diagrams.
AB  - Although many mechanisms have been proposed to explain the microbiologically
      assisted cracking (MAC) of steel and copper, a theoretical interpretation is
      necessary. In this paper, we attempt to give a theoretical interpretation of
      sulfate/nitrate reducing bacteria (SRB/NRB)-assisted cracking using Ee-pH
      diagrams. Under the combined actions of SRB/NRB and external stress, the cell
      potential (Ecell) and the corrosion current density of the corrosion reaction
      increase, such that the corrosion reactions become more thermodynamically
      favorable. This is the nature of MAC. Nitrate is a far more potent oxidant than
      sulfate, and thus, the NRB-assisted cracking of iron is a more thermodynamically
      favorable process than the SRB-assisted cracking. Furthermore, the thermodynamic
      interpretation is attempted to implicate into the classical stress corrosion
      cracking mechanisms of pipeline steel.

PMID- 29175693
TI  - Influence of valproate on language functions in children with epilepsy.
AB  - The aim of the current study was to assess the influences of valproate (VPA) on
      the language functions in newly diagnosed pediatric patients with epilepsy. We
      reviewed medical records of 53 newly diagnosed patients with epilepsy, who were
      being treated with VPA monotherapy (n=53; 22 male patients and 31 female
      patients). The subjects underwent standardized language tests, at least twice,
      before and after the initiation of VPA. The standardized language tests used were
      The Test of Language Problem Solving Abilities, a Korean version of The
      Expressive/Receptive Language Function Test, and the Urimal Test of Articulation
      and Phonology. Since all the patients analyzed spoke Korean as their first
      language, we used Korean language tests to reduce the bias within the data. All
      the language parameters of the Test of Language Problem Solving Abilities
      slightly improved after the initiation of VPA in the 53 pediatric patients with
      epilepsy (mean age: 11.6+/-3.2years), but only "prediction" was statistically
      significant (determining cause, 14.9+/-5.1 to 15.5+/-4.3; making inference,
      16.1+/-5.8 to 16.9+/-5.6; prediction, 11.1+/-4.9 to 11.9+/-4.2; total score of
      TOPS, 42.0+/-14.4 to 44.2+/-12.5). The patients treated with VPA also exhibited a
      small extension in mean length of utterance in words (MLU-w) when responding, but
      this was not statistically significant (determining cause, 5.4+/-2.0 to 5.7+/
      1.6; making inference, 5.8+/-2.2 to 6.0+/-1.8; prediction, 5.9+/-2.5 to 5.9+/
      2.1; total, 5.7+/-2.1 to 5.9+/-1.7). The administration of VPA led to a slight,
      but not statistically significant, improvement in the receptive language function
      (range: 144.7+/-41.1 to 148.2+/-39.7). Finally, there were no statistically
      significant changes in the percentage of articulation performance after taking
      VPA. Therefore, our data suggested that VPA did not have negative impact on the
      language function, but rather slightly improved problem-solving abilities.

PMID- 29175694
TI  - Diagnostic accuracy of paroxysmal spells: Clinical history versus observation.
AB  - Our goal was to evaluate how accurate neurologists are at differentiating between
      different paroxysmal events based on clinical history versus observation of the
      spell in question. Forty-seven neurologists reviewed 12 clinical histories and
      videos of recorded events of patients admitted in the Epilepsy Monitoring Unit
      (EMU). They were asked to diagnose events as epileptic seizures, non-epileptic
      behavioral spells (NEBS), or other physiologic events as well as rate their
      confidence in their diagnosis. The median diagnostic accuracy for all paroxysmal
      events was 67% for clinical history and 75% for observation (p=.001). This was
      largely due to the difference in accuracy within the subgroup of patients with
      NEBS (67% history vs. 83% observation, p<.001). There were trends for higher
      diagnostic accuracy and increased inter-rater agreement with higher levels of
      training. Physicians with higher levels of training were more confident with
      diagnosis based on observation. In summary, reviewing videos of paroxysmal spells
      may improve diagnostic accuracy and enhance the evaluation of patients.
      Neurologists at all levels of training should encourage the recording and review
      of videos of recurrent spells to aid in medical decision-making especially when
      there is high concern that the spells in question are NEBS.

PMID- 29175695
TI  - Determination of non-liposomal and liposomal doxorubicin in plasma by LC-MS/MS
      coupled with an effective solid phase extraction: In comparison with
      ultrafiltration technique and application to a pharmacokinetic study.
AB  - Liposomal formulation of doxorubicin has been widely applied in clinic for
      treatment of various cancers. The separation and measurement of free drug (drug
      which is not entrapped in liposomes) and liposomal drug in the plasma after
      injection of liposomal doxorubicin is of prime importance due to toxicity and
      activity concerns. In this study, a rapid and convenient method was developed to
      isolate and determine the non-liposomal and liposomal drugs in plasma. Plasma
      samples were prepared by solid phase extraction (SPE) using Oasis HLB cartridges.
      Liposomal doxorubicin (L-DOX) was collected in the aqueous eluate with its
      internal standard (IS), metformin; and non-liposomal doxorubicin (NL-DOX) and its
      isotope labelling IS were eluted from the cartridge by methanol containing 0.5%
      formic acid. After SPE separation, L-DOX and NL-DOX were subsequently quantified
      by a validated sensitive LC-MS/MS method individually. The calibration curves
      were found to be linear for L-DOX in the range of 0.156-40.0MUg/mL and for NL-DOX
      in the range of 3.13-200ng/mL. The extraction recovery was about 97% for L-DOX
      and about 65% for NL-DOX. This method was further applied to investigate the
      pharmacokinetics of doxorubicin in Beagle dogs after an intravenous dose of
      1.0mg/kg Doxil(r). After injection of Doxil(r), L-DOX was the predominant
      component circulating in plasma, whose amount was about 1000-fold higher than
      that of NL-DOX. The analytical method might be helpful in pharmacokinetics and
      toxicity assessment of liposomal formulation.

PMID- 29175696
TI  - Determination of adrenaline, noradrenaline and corticosterone in rodent blood by
      ion pair reversed phase UHPLC-MS/MS.
AB  - A novel ion pair reversed phase ultra high performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of
      the stress hormones adrenaline, noradrenaline and corticosterone in rodent blood
      was developed and fully validated. Separations were performed on an Acquity HSS
      T3 column (2.1mm i.d.*100mm, 1.8MUm) with gradient elution and a runtime of
      5.5min. The retention of adrenaline and noradrenaline was substantially increased
      by employing the ion pair reagent heptafluorobutyric acid (HFBA). Ion pair
      reagents are usually added to the mobile phase only, but we demonstrate for the
      first time that including HFBA to the sample reconstitution solvent as well, has
      a major impact on the chromatography of these compounds. The stability of
      adrenaline and corticosterone in rodent blood was investigated using the
      surrogate analytes adrenaline-d3 and corticosterone-d8. The applicability of the
      described method was demonstrated by measuring the concentration of stress
      hormones in rodent blood samples.

PMID- 29175697
TI  - In vivo study of erysolin metabolic profile by ultra high performance liquid
      chromatography coupleded to Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - An ultra high performance liquid chromatography coupled to Fourier transform ion
      cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) method was developed for
      the first time to study the in vivo metabolism of erysolin, a compound derived
      from cruciferous plants which has a definite effect of anti-tumor and anti-nerve
      injury. In this research, the chromatographic separation was performed on an
      ACQUITY UPLC(r) BEH C18 column (2.1 mm*100mm, 1.7MUm, Waters, USA) and eluted by
      a gradient program, the identification work was achieved on a Bruker ultra-high
      resolution spectrometer in positive ion mode. Plasma, urine, feces and bile
      samples were collected from rats to screen metabolites after an intragastric
      administration of erysolin at the dose of 100mg/kg. As a result, the parent drug
      and a total of six phase II metabolites were detected and preliminarily
      identified by analyzing their MS and MS/MS spectrometry profiles. Our results
      indicated that erysolin mainly metabolized via the mercapturic acid metabolic
      pathway, erysolin first react with glutathione to form glutathione conjugate,
      followed by taking off the glutamic acid and glycine to form cysteine conjugate,
      then the N-acetylation reaction occurs, the product would be excreted out of the
      body at last. In conclusion, results obtained in our study may contribute to a
      better understanding of the metabolism process and characteristics of erysolin in
      vivo, and provide an important reference for future research.

PMID- 29175698
TI  - Lipophilicity assessement in drug discovery: Experimental and theoretical methods
      applied to xanthone derivatives.
AB  - For the last several years, searching of new xanthone derivatives (XDs) with
      potential pharmacological activities has remained one of the main areas of
      interest of our group. The optimization of biological activity and drug-like
      properties of hits and leads is crucial at early stage of the drug discovery
      pipeline. Lipophilicity is one of the most important drug-like properties having
      a great impact in both pharmacokinetics and pharmacodynamics processes. In this
      work, we describe the lipophilicity of a small library of bioactive XDs,
      previously synthesized by our group, using different methods: computational,
      vortex-assisted liquid-liquid microextraction coupled with high-performance
      liquid chromatography (VALLME-HPLC), reversed-phase high-performance thin layer
      chromatography (RP-HPTLC), reversed-phase high-performance liquid chromatography
      (RP-HPLC), and biomembrane model by the partition between micelles and aqueous
      phase. The different results obtained by the used methods were compared and
      discussed. The methodologies and data gathered in this study will expand the
      investigation of lipophilicity of XDs, an important class of compounds in
      medicinal chemistry.

PMID- 29175699
TI  - "Do-it-yourself": Vaccine rejection and complementary and alternative medicine
      (CAM).
AB  - In this article, we elucidate a symbiotic relationship between complementary and
      alternative medicine (CAM) and rejection of, or hesitancy towards, vaccination.
      In Fremantle, Western Australia, and Adelaide, South Australia, we conducted in
      depth interviews from September 2013-December 2015 with 29 parents who had
      refused or delayed some or all of their children's vaccines. Our qualitative
      analysis found that for many, their do-it-yourself ethic and personal agency was
      enhanced by self-directed CAM use, alongside (sometimes informal) CAM
      practitioner instruction. Reifying 'the natural,' these parents eschewed vaccines
      as toxic and adulterating, and embraced CAM as a protective strategy for immune
      systems before, during and after illness. Users saw CAM as harm-free, and when it
      came to experiences that non-users might interpret as demonstrating CAM's
      ineffectiveness, they rationalised to the contrary. They also generally glossed
      over its profit motive. CAM emerged as part of an expert system countering
      Western medicine. CAM's faces were trusted and familiar, and its cottage
      capitalism appeared largely free from the taint of "Big Pharma." A few parents
      employed a scientific critique of CAM modalities - and a minority were dubious of
      its profit motive - but others rejected the epistemology underpinning
      biomedicine, framing CAM as a knowledge not poisoned by avarice; a wisdom whose
      very evidence-base (anecdote and history) was demeaned by an arrogant scientific
      process only permitting belief in that which could be quantified. However, all
      parents engaged with Western medicine for broken bones and, sometimes, medical
      diagnoses. Our analysis suggests that pro-vaccination health professionals,
      policymakers and information-providers seeking to address the role of CAM in
      vaccine rejection face significant challenges due to the epistemic basis of some
      parents' decisions. However, we make some suggestions for professional practice
      and policy to enhance trust in vaccination.

PMID- 29175700
TI  - Social capital, income inequality and the social gradient in self-rated health in
      Latin America: A fixed effects analysis.
AB  - Latin America is the most unequal region in the world. The current sustainable
      development agenda increased attention to health inequity and its determinants in
      the region. Our aim is to investigate the social gradient in health in Latin
      America and assess the effects of social capital and income inequality on it. We
      used cross-sectional data from the World Values Survey and the World Bank. Our
      sample included 10,426 respondents in eight Latin American countries. Self-rated
      health was used as the outcome. Education level was the socioeconomic position
      indicator. We measured social capital by associational membership, civic
      participation, generalized trust, and neighborhood trust indicators at both
      individual and country levels. Income inequality was operationalized using the
      Gini index at country-level. We employed fixed effects logistic regressions and
      cross-level interactions to assess the impact of social capital and income
      inequality on the heath gradient, controlling for country heterogeneity.
      Education level was independently associated with self-rated health, representing
      a clear social gradient in health, favoring individuals in higher socioeconomic
      positions. Generalized and neighborhood trust at country-level moderated the
      effect on the association between socioeconomic position and health, yet favoring
      individuals in lower socioeconomic positions, especially in lower inequality
      countries, despite their lower individual social capital. Our findings suggest
      that collective rather than individual social capital can impact the social
      gradient in health in Latin America, explaining health inequalities.

PMID- 29175701
TI  - From therapeutic landscapes to healthy spaces, places and practices: A scoping
      review.
AB  - The term 'therapeutic landscapes' was first coined by health geographer, Wilbert
      Gesler, in 1992 to explore why certain environments seem to contribute to a
      healing sense of place. Since then, the concept and its applications have evolved
      and expanded as researchers have examined the dynamic material, affective and
      socio-cultural roots and routes to experiences of health and wellbeing in
      specific places. Drawing on a scoping review of studies of these wider
      therapeutic landscapes published between 2007 and 2016, this paper explores how,
      where, and to what benefit the 'therapeutic landscapes' concept has been applied
      to date, and how such applications have contributed to its critical evolution as
      a relevant and useful concept in health geography. Building on themes included in
      two earlier (1999, 2007) edited volumes on Therapeutic Landscapes, we summarise
      the key themes identified in the review, broadly in keeping with the core
      material, social, spiritual and symbolic dimensions of the concept initially
      posited by Gesler. Through this process, we identify strengths and limitations of
      the concept and its applications, as well as knowledge gaps and promising future
      directions for work in this field, reflecting critically on its value within
      health geography and its potential contribution to wider interdisciplinary
      discussions and debates around 'healthy' spaces, places, and related practices.

PMID- 29175702
TI  - Government health insurance and spatial peer effects: New evidence from India.
AB  - What is the role of spatial peers in diffusion of information about health care?
      We use the implementation of a health insurance program in Karnataka, India that
      provided free tertiary care to poor households to explore this issue. We use
      administrative data on location of patient, condition for which the patient was
      hospitalized and date of hospitalization (10,507 observations) from this program
      starting November 2009 to June 2011 for 19 months to analyze spatial and temporal
      clustering of tertiary care. We find that the use of healthcare today is
      associated with an increase in healthcare use in the same local area (group of
      villages) in future time periods and this association persists even after we
      control for (1) local area fixed effects to account for time invariant factors
      related to disease prevalence and (2) local area specific time fixed effects to
      control for differential trends in health and insurance related outreach
      activities. In particular, we find that 1 new hospitalization today results in
      0.35 additional future hospitalizations for the same condition in the same local
      area. We also document that these effects are stronger in densely populated areas
      and become pronounced as the insurance program becomes more mature suggesting
      that word of mouth diffusion of information might be an explanation for our
      findings. We conclude by discussing implications of our results for healthcare
      policy in developing economies.

PMID- 29175703
TI  - Omics-based natural product discovery and the lexicon of genome mining.
AB  - Genome sequencing and the application of omic techniques are driving many
      important advances in the field of microbial natural products research. Despite
      these gains, there remain aspects of the natural product discovery pipeline where
      our knowledge remains poor. These include the extent to which biosynthetic gene
      clusters are transcriptionally active in native microbes, the temporal dynamics
      of transcription, translation, and natural product assembly, as well as the
      relationships between small molecule production and detection. Here we touch on a
      number of these concepts in the context of continuing efforts to unlock the
      natural product potential revealed in genome sequence data and discuss
      nomenclatural issues that warrant consideration as the field moves forward.

PMID- 29175704
TI  - Synthesis and mechanistic investigation of iron(II) complexes of isoniazid and
      derivatives as a redox-mediated activation strategy for anti-tuberculosis
      therapy.
AB  - The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MTB)
      represents a major threat to global health. Isoniazid (INH) is a prodrug used in
      the first-line treatment of tuberculosis. It undergoes oxidation by a catalase
      peroxidase KatG, leading to generation of an isonicotinoyl radical that reacts
      with NAD(H) forming the INH-NADH adduct as the active metabolite. A redox
      mediated activation of isoniazid using an iron metal complex was previously
      proposed as a strategy to overcome isoniazid resistance due to KatG mutations.
      Here, we have prepared a series of iron metal complexes with isoniazid and
      analogues, containing alkyl substituents at the hydrazide moiety, and also with
      pyrazinamide derivatives. These complexes were activated by H2O2 and studied by
      ESR and LC-MS. For the first time, the formation of the oxidized INH-NAD adduct
      from the pentacyano(isoniazid)ferrate(II) complex was detected by LC-MS,
      supporting a redox-mediated activation, for which a mechanistic proposition is
      reported. ESR data showed all alkylated hydrazides, in contrast to non
      substituted hydrazides, only generated alkyl-based radicals. The structural
      modifications did not improve minimal inhibitory concentration (MIC) against MTB
      in comparison to isoniazid iron complex, providing support to isonicotinoyl
      radical formation as a requirement for activity. Nonetheless, the pyrazinoic acid
      hydrazide iron complex showed redox-mediated activation using H2O2 with
      generation of a pyrazinoyl radical intermediate and production of pyrazinoic
      acid, which is in fact the active metabolite of pyrazinamide prodrug. Thereby,
      this strategy can also unveil new opportunities for activation of this type of
      drug.

PMID- 29175706
TI  - Implicit memory of locations and identities: A developmental study.
AB  - Objects in the environment have both location and identity properties. However,
      it is unclear how these independent properties are processed and combined in the
      implicit domain. The current study investigated the development of the implicit
      memory of object locations and object identities, both independently and
      combined, and the relation between implicit memory and working memory (WM) for
      these properties. Three age groups participated: 6- and 7-year-old children, 9-
      and 10-year-old children, and adults. Children and adults completed a repeated
      search paradigm. In the learning phase, targets' locations were consistently
      predicted by both the identities and locations of the distracters. In the test
      phase, either both remained predictive or just the identities or just the
      locations of the distracters predicted the location of the target. All groups
      showed significant implicit learning when both the identities and locations of
      the distracters remained predictive. When only the locations but not the
      identities of the distracters were predictive, adults and 9- and 10-year-olds
      showed significant learning, whereas 6- and 7-year-olds did not. When only the
      identities but not the locations of the distracters were predictive, none of the
      groups showed significant learning effects. In evaluating the contributions of
      either visual or spatial WM to implicit learning and memory, we found that
      children with smaller visual WM exhibited larger implicit memory effects for
      object identities than did children with larger visual WM. Taken together, the
      results indicate that children's ability to differentiate identity and location
      undergoes development even in the implicit domain.

PMID- 29175707
TI  - Using the glycan toolbox for pathogenic interventions and glycan immunotherapy.
AB  - Glycans play a crucial role to discern between self and foreign entities by
      providing key recognition elements for C-type lectin receptors (CLRs) and Siglec
      receptors expressed on immune cells. The glycan recognition of CLRs has
      illustrated a potent immune modulatory role affecting not only innate pathogen
      binding and immune signalling, but also Thelper differentiation, cytokine
      production and antigen presentation. This broad range of influence has implicated
      glycans in the pathogenesis of infectious diseases but also revealed their
      extraordinary properties in cancer. Glycan binding by CLRs and Siglecs can be
      exploited for immunotherapy and the design of glycan-based therapeutics and their
      multivalent requirements will aspire new biotechnological approaches to
      effectively interfere in immunological processes in cancer and infectious
      diseases.

PMID- 29175705
TI  - Quantifying attentional effects on the fidelity and biases of visual working
      memory in young children.
AB  - Attentional control enables us to direct our limited resources to accomplish
      goals. The ability to flexibly allocate resources helps to prioritize information
      and inhibit irrelevant/distracting information. We examined developmental changes
      in visual working memory (VWM) fidelity in 4- to 7-year-old children and the
      effects that a distracting non-target object can exert in biasing their memory
      representations. First, we showed that VWM fidelity improves from early childhood
      to adulthood. Second, we found evidence of working memory load on recall
      variability in children and adults. Next, using cues to manipulate attention, we
      found that older children are able to construct a more durable memory
      representation for an object presented following a non-target using a pre-cue
      (that biases encoding before presentation) compared with a retro-cue (that
      signals which item to recall after presentation). In addition, younger children
      had greater difficulties maintaining an item in memory when an intervening item
      was presented. Lastly, we found that memory representations are biased toward a
      non-target when it is presented following the target and away from a non-target
      when it precedes the target. These bias effects were more pronounced in children
      compared with adults. Together, these results demonstrate changes in attention
      over development that influence VWM memory fidelity.

PMID- 29175708
TI  - Engineering of biomolecules by bacteriophage directed evolution.
AB  - Conventional in vivo directed evolution methods have primarily linked the
      biomolecule's activity to bacterial cell growth. Recent developments instead rely
      on the conditional growth of bacteriophages (phages), viruses that infect and
      replicate within bacteria. Here we review recent phage-based selection systems
      for in vivo directed evolution. These approaches have been applied to evolve a
      wide range of proteins including transcription factors, polymerases, proteases,
      DNA-binding proteins, and protein-protein interactions. Advances in this field
      expand the possible applications of protein and RNA engineering. This will
      ultimately result in new biomolecules with tailor-made properties, as well as
      giving us a better understanding of basic evolutionary processes.

PMID- 29175709
TI  - Alpha7 nicotinic acetylcholine receptor-specific agonist DMXBA (GTS-21)
      attenuates Abeta accumulation through suppression of neuronal gamma-secretase
      activity and promotion of microglial amyloid-beta phagocytosis and ameliorates
      cognitive impairment in a mouse model of Alzheimer's disease.
AB  - We previously demonstrated that stimulation of nicotinic acetylcholine receptors
      (nAChRs) increases amyloid-beta (Abeta) phagocytosis in rat microglia and is
      closely associated with the decrease of brain Abeta and amelioration of memory
      dysfunction in a transgenic mouse model of Alzheimer's disease (AD). Here, we
      examined the subtypes of nAChRs involved in these beneficial effects. In primary
      cultures of rat microglia, the alpha7 nAChR selective agonist 3-[(2,4
      dimethoxy)benzylidene]-anabaseine dihydrochloride (DMXBA) promoted Abeta and
      fluorescent latex bead phagocytosis, whereas selective alpha7 nAChR antagonists
      suppressed the enhanced Abeta phagocytosis. In a transgenic mouse model of AD,
      administration of DMXBA attenuated brain Abeta burden and memory dysfunction.
      Moreover, DMXBA suppressed gamma-secretase activity in solubilized fractions of
      human neuroblastoma cells and transgenic mouse brain. These results suggested
      that selective activation of alpha7 nAChRs promoted microglial Abeta phagocytosis
      and suppressed neuronal gamma-secretase activity to contribute to the attenuation
      of the brain Abeta burden and cognitive impairment. Thus, we propose neuronal and
      microglial alpha7 nAChRs as new therapeutic targets in the treatment of AD.

PMID- 29175710
TI  - EEG correlates of visual short-term memory in older age vary with adult lifespan
      cognitive development.
AB  - Visual short-term memory (vSTM) is a cognitive resource that declines with age.
      This study investigated whether electroencephalography (EEG) correlates of vSTM
      vary with cognitive development over individuals' lifespan. We measured vSTM
      performance and EEG in a lateralized whole-report task in a healthy birth cohort,
      whose cognitive function (intelligence quotient) was assessed in youth and late
      middle age. Higher vSTM capacity (K; measured by Bundesen's theory of visual
      attention) was associated with higher amplitudes of the contralateral delay
      activity (CDA) and the central positivity (CP). In addition, rightward hemifield
      asymmetry of vSTM (Klambda) was associated with lower CDA amplitudes.
      Furthermore, more severe cognitive decline from young adulthood to late-middle
      age predicted higher CDA amplitudes, and the relationship between K and the CDA
      was less reliable in individuals who show higher levels of cognitive decline
      compared to individuals with preserved abilities. By contrast, there was no
      significant effect of lifespan cognitive changes on the CP or the relationship
      between behavioral measures of vSTM and the CP. Neither the CDA, nor the CP, nor
      the relationships between K or Klambda and the event-related potentials were
      predicted by individuals' current cognitive status. Together, our findings
      indicate complex age-related changes in processes underlying behavioral and EEG
      measures of vSTM and suggest that the K-CDA relationship might be a marker of
      cognitive lifespan trajectories.

PMID- 29175711
TI  - Evidence for estrogeno-mimetic effects of a mixture of low-dose pollutants in a
      model of ovariectomized mice.
AB  - We recently hypothesized that a mixture of low-dosed dioxin, polychlorobiphenyl,
      phthalate and bisphenol may induce estrogeno-mimetic activities in a model of
      lifelong-exposed female mice. Herein, we evaluated the impact of this mixture in
      estrogen deficiency conditions. Based on the protective effects of estrogens
      against metabolic disorders, we reasoned that exposure to pollutants should
      attenuate the deleterious metabolic effects induced by ovariectomy. In line with
      the hypothesis, exposure to pollutants was found to reduce the impact of
      ovariectomy on glucose intolerance and insulin resistance, to enhance the
      expression levels of the hepatic estrogen receptor alpha and to attenuate the
      ovariectomy-induced enhancement of the chemokine MCP-1/CCL2 considered as an
      indicator of estrogen signalling. Because of the very low doses of pollutants
      used in mixture, these findings may have strong implications in terms of
      understanding the potential role of environmental contaminants in the development
      of metabolic diseases, specifically in females during menopausal transition.

PMID- 29175712
TI  - Fabrication of capsaicin functionalized reduced graphene oxide and its effect on
      proliferation and differentiation of osteoblasts.
AB  - Herein, we report a new simple and biological approach for the preparation of
      capsaicin adsorbed reduced graphene oxide (RGO), where capsaicin acts as a
      stabilizing and deoxygenating agent. The capsaicin that is decorated on graphene
      surface plays an important role as a capping agent to avoid the aggregation of
      graphene sheets. The capsaicin functionalized RGO stimulated the differentiation
      and proliferation of osteoblasts to a larger extent, which is a significant
      feature for the use of biomaterials in biomedical application such as in bone
      tissue engineering, more speciafically in the case of diseases such as
      osteoporosis.

PMID- 29175713
TI  - Lateral habenula in the pathophysiology of depression.
AB  - Depression is a devastating disorder with a combination of diverse symptoms such
      as low self-esteem, lack of motivation, anhedonia, loss of appetite, low energy,
      and discomfort without a clear cause. Depression has been suggested to be the
      result of maladaptive changes in specific brain circuits. Recently, the lateral
      habenula (LHb) has emerged as a key brain region in the pathophysiology of
      depression. Increasing evidence from rodent, non-human primate and human studies
      indicates that the aberrant activity of the LHb is associated with depressive
      symptoms such as helplessness, anhedonia, and excessive negative focus. Revealing
      the molecular, cellular and circuit properties of the LHb will help explain how
      abnormalities in LHb activity are linked to depressive disorders, and shed light
      on developing novel strategies for depression treatment.

PMID- 29175714
TI  - The effect of additional activation of the plantar intrinsic foot muscles on foot
      dynamics during gait.
AB  - BACKGROUND: The plantar intrinsic foot muscles (PIFMs) contribute to support the
      medial longitudinal arch. But the functional role of the PIFMs during dynamic
      activities is not clear. The purpose of this study was to examine the change in
      the foot dynamics during gait accompanied with the change in the PIFMs activity
      to determine the functional role of the PIFMs during gait. METHODS: Twenty
      healthy male subjects were randomly assigned to the electrical stimulation group
      (ESG) or control group (CG). In the ESG, the electrical stimulation to the PIFMs
      was provided from mid-stance to pre-swing using surface electrodes to simulate
      reinforcement of the PIFMs. The foot dynamics during the stance phase of gait was
      measured using a 3D motion analysis, and the amount of change from baseline
      (electrical stimulation was not provided) was compared between groups using an
      independent sample t-test. RESULTS: In the ESG, the timing for the navicular
      height to reach the minimum value was significantly later, and the vertical
      ground reaction force (2nd peak) significantly decreased more. There were no
      group differences in the amount of change from baseline on gait velocity, stance
      phase duration, minimum navicular height and ground reaction force in other
      directions. CONCLUSION: Results from this study showed that the functions of the
      PIFMs most likely include shock absorption and facilitation of efficient foot
      ground force transmission during the stance phase of gait.

PMID- 29175715
TI  - Manual therapy for plantar heel pain.
AB  - BACKGROUND: Manual therapy employed in the treatment of plantar heel pain
      includes joint or soft tissue mobilizations. Efficacy of these methods is still
      under debate. AIMS: To determine whether manual therapy, consisting of deep
      massage, myofascial release or joint mobilization is effective in treating
      plantar heel pain. METHODS: A critical review of all available studies with an
      emphasis on randomized controlled trials (RCTs) was performed. PubMed, PEDro, and
      Google Scholar databases were searched for keywords relating to plantar heel
      pain, joint, and soft tissue mobilizations. There were no search limitations or
      language restrictions. The reference lists of all retrieved articles were
      searched. The PEDro score was used to assess the quality of the reviewed papers.
      RESULTS: A total of six relevant RCTs were found: two examined the effectiveness
      of joint mobilization on plantar heel pain and four the effectiveness of soft
      tissue techniques. Five studies showed a positive short-term effect after manual
      therapy treatment, mostly soft tissue mobilizations, with or without stretching
      exercises for patients with plantar heel pain, compared to other treatments. One
      study observed that adding joint mobilization to the treatment of plantar heel
      pain was not effective. The quality of all studies was moderate to high.
      CONCLUSIONS: According to reviewed moderate and high-quality RCTs, soft tissue
      mobilization is an effective modality for treating plantar heel pain. Outcomes of
      joint mobilizations are controversial. Further studies are needed to evaluate the
      short and long-term effect of different soft tissue mobilization techniques.

PMID- 29175716
TI  - Diabetes foot screening: Current practice and the future.

PMID- 29175717
TI  - Tibio-calcaneal fusion by retrograde intramedullary nailing in charcot
      neuroarthropathy.
AB  - INTRODUCTION: Charcot's neuroarthropathy of ankle leads to instability,
      destruction of the joint with significant morbidity that may require an
      amputation. Aim of surgical treatment is to achieve painless stable plantigrade
      foot through arthrodesis. Achieving surgical arthrodesis in Charcot's
      neuroarthropathy has a high failure rate. We assess the outcomes of retrograde
      intramedullary interlocked nailing in tibio-talar arthrodesis for Charcot's
      neuroarthropathy. MATERIALS AND METHODS: 42 diabetic patients with a mean age of
      49 year underwent ankle tibio-talar arthrodesis using retrograde nailing for
      Charcot's neuroarthropathy. The postoperative complications have been discussed
      and their management outlined. The outcomes were measured radiologically and
      clinically. Follow up was done after 6 weeks, 3 months, 6 months and 1 year.
      RESULTS: 14 patients (33.3%) achieved uneventful uncomplicated fusion. Thirty
      three patients had varus deformity. Nine patients had valgus deformity. Using
      Paired t test, it showed statistically significant improvement in the functional
      outcomes (AOFAS& EQ-5D-5L) over the follow up time, despite of the mild
      deterioration of radiological angles in the final follow up visit compared to the
      postoperative radiological findings. CONCLUSION: Retrograde nailing is one of the
      best options for tibio-talo-calcaneal arthrodesis in the high-risk Charcot's
      neuroarthropathy population. It could be done through small incisions with lower
      soft tissue complications, its load-sharing properties allows a considerable
      compression across the ankle and talocalcaneal joints with early weight bearing
      and with satisfactory functional outcomes.

PMID- 29175718
TI  - Does sound structure affect word learning? An eye-tracking study of Danish
      learning toddlers.
AB  - Previous research has shown that Danish-learning children lag behind in early
      lexical acquisition compared with children learning a number of other languages.
      This delay has been ascribed to the opaque phonetic structure of Danish, which
      appears to have fewer reliable segmentation cues than other closely related
      languages. In support of this hypothesis, recent work has shown that the phonetic
      properties of Danish negatively affect online language processing in young Danish
      children. In this study, we used eye-tracking to investigate whether the
      challenges associated with processing Danish also affect how Danish-learning
      children between 24 and 35 months of age establish and learn novel label-object
      mappings. The children were presented with a series of novel mappings, either
      ostensively (one novel object presented alone on the screen) or ambiguously (one
      novel object presented together with a familiar one), through carrier phrases
      with different phonetic structures (more vs less opaque). Our results showed two
      main trends. First, Danish-learning children performed poorly on the task of
      mapping novel labels onto novel objects. Second, when learning did occur,
      accuracy was affected by the phonetic opacity of the speech stimuli. We suggest
      that this finding results from the interplay of a perceptually challenging speech
      input and a slower onset of early vocabulary experience, which in turn may delay
      the onset of word learning skills in Danish-learning children.

PMID- 29175719
TI  - Does chronic ankle instability influence lower extremity muscle activation of
      females during landing?
AB  - Much remains unclear about how chronic ankle instability (CAI) could affect knee
      muscle activations and interact with knee biomechanics. Therefore, the purpose of
      this study was to assess the influence of CAI on the lower extremity muscle
      activation at the ankle and knee joints during landings on a tilted surface. A
      surface electromyography system and two force plates were used to collect lower
      extremity muscle activation of 21 young female individuals with CAI and 21 pair
      matched controls during a double-leg landing with test limb landing on the tilted
      surface. In the pre-landing phase, compared to controls, CAI participants
      displayed a reduced ankle evertor activation that could place CAI at a high risk
      of giving way or sprain injury. In the landing phase, an increased tibialis
      anterior activation of CAI led to increased co-contraction of ankle muscles in
      the sagittal and frontal plane. A greater ankle muscle co-contraction could
      increase the ankle stability during landings but may adversely influence the knee
      muscle activations (e.g., a greater co-contraction ratio of quadriceps to
      hamstrings). Relevant training programs (e.g., increasing pre-landing peroneal
      activation, and optimizing activation ratio of quadriceps to hamstrings) may help
      individuals with CAI improving ankle stability and reduce atypical knee loading
      during landings.

PMID- 29175720
TI  - T4 and waist:hip ratio as biomarkers of antipsychotic-induced weight gain in Han
      Chinese inpatients with schizophrenia.
AB  - Second-generation antipsychotic agents (SGAs) cause serious metabolic side
      effects, including weight gain, dyslipidemia, and glucose metabolism
      abnormalities, which occur by unknown mechanisms. Therefore, the search for
      prospective markers for antipsychotic-induced weight gain (AIWG) has been of
      major interest. So far, predictive factors predisposing patients to the develop
      obesity and related metabolic disturbances induced by SGAs have been relatively
      less studied among large samples of Chinese schizophrenic patients. In this
      study, 264 Han Chinese inpatients diagnosed with schizophrenia or schizoaffective
      disorder initiated treatment with olanzapine (n=131) or risperidone (n=133) and
      were followed for 12weeks. Anthropometric measurements and laboratory analyses of
      thyroid hormone, fasting plasma glucose (FPG), and lipid levels were conducted as
      part of routine medical care. The results showed baseline thyroxine (T4) and
      waist:hip ratio (WHR)were negatively correlated to AIWG (T4: rs=-0.154, P=0.014;
      WHR: rs=-0.199, P=0.008). Correlations remained significant after multiple
      regression analyses. The two treatment groups statistically differed for changes
      in body mass index, WHR, LDL cholesterol, and FPG; in both groups FPG decreased
      at first and then increased. Our findings suggest basal T4 and WHR may serve as
      early biomarkers for weight gain as a side effect of single-SGA treatment.

PMID- 29175721
TI  - De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with
      affective function.
AB  - Despite the high prevalence of panhypopituitarism and diabetes insipidus in
      patients with craniopharyngioma (CP), little is known about the functioning of
      the neuropeptide oxytocin in these patients. This is of special interest as tumor
      associated lesions often impair sites critical for oxytocin production and
      release, and affective dysfunction in CP links with elsewhere reported prosocial,
      antidepressant and anxiolytic oxytocin effects. Using a prospective study-design,
      we tested whether oxytocin is reduced in CP-patients, and whether altered
      oxytocin levels account for affective and emotional dysfunction. 26 adult CP
      patients and 26 healthy controls matched in sex and age underwent physical
      exercise, a stimulus previously shown to induce oxytocin release. Baseline and
      stimulated salivary oxytocin levels, as well as empathy, depression and anxiety
      scores were measured. Results showed that patients overall did not present with
      lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but
      baseline oxytocin levels were indeed reduced in patients with hypothalamic
      damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response
      to exercise-induced stimulation, all CP-patients showed a blunted oxytocin
      release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with
      oxytocin levels. Regarding affective function, unexpectedly, higher baseline
      oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020,
      CI[.478; 5.292]); the positive link with higher depression failed to reach
      statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A
      blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=
      2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin
      measures. In conclusion, we observed reduced baseline oxytocin levels only in CP
      patients with hypothalamic damage. Exercise-induced stimulation de-masked an
      oxytocin-deficiency in all CP-patients. Baseline oxytocin levels and stimulated
      OT-responses might have different effects on affective function, which should be
      considered in future substitution paradigms.

PMID- 29175722
TI  - Significance of systemic immune-inflammation index in the differential diagnosis
      of high- and low-grade gliomas.
AB  - OBJECTIVE: Circulating biomarkers have been increasingly appreciated in the
      grading of gliomas. This study aimed to assess the value of the systemic immune
      inflammation index (SII) as a possible marker in the grading of gliomas.
      MATERIALS AND METHODS: In our study, 153 patients with gliomas were included-53
      patients had histologically verified low grade gliomas (LGG) and 100 patients had
      high grade gliomas (HGG). Preoperative complete blood count (CBC) and
      clinicopathological data were collected. The optimal SII cut-off value for
      grading of gliomas was calculated by receiver operating characteristics curve
      (ROC) analysis. RESULTS: Based on the ROC analysis, the most optimal cut-off
      value of SII to distinguish HGG and LGG was determined as 392.48*109/L. For this
      cut-off value, SII had a sensitivity of 75%, specificity of 66%, and area under
      the curve (AUC) of 0.773. Furthermore, we found that patients in the high-SII
      group had a significantly higher Ki-67 index than that in patients in the low-SII
      group (P=0.002). CONCLUSION: Our results demonstrate that SII has a moderate
      diagnostic accuracy for differentiating HGG from LGG. More studies are needed to
      confirm these results.

PMID- 29175723
TI  - Brain tumors associated with psychogenic non-epileptic seizures: Case series.
AB  - OBJECTIVE: The association of psychogenic non-epileptic seizures (PNES) with
      primary or secondary brain tumors has not been well described in the literature.
      We aim to discuss their association, and their impact in brain tumor treatment.
      PATIENTS AND METHODS: We identified four patients retrospectively from our
      practice. The diagnosis of PNES was based on clinical suspicion and standard EEG,
      supplemented with video-EEG recording in 2 patients. RESULTS: The initial
      diagnosis of brain tumor was associated with a new onset seizure prior to
      diagnosis. The majority of the patients presented with ES followed by recurrent
      PNES during the course of their disease. Patients were treated with multiple anti
      epileptic drugs, requiring frequent schedule adjustments. The preferred tumor
      treatment modality was chemotherapy, followed by surgical resection. The patients
      were offered psychological consultation achieving partial control of their
      events. These patients manifested recurrent disabling clinical events that
      required multiple medical consultations. None of these patients presented
      clinical evidence of tumor progression at the time of PNES presentation.
      CONCLUSION: A high index of suspicion and early psychological consultation
      referral will likely mitigate the quality of life impact of PNES in these
      patients.

PMID- 29175724
TI  - A right amygdalohippocampectomy: A diagnostic challenge.
AB  - OBJECTIVE: Amygdalohippocampectomy (AHE) is the resective surgery for medically
      intractable mesial temporal lobe epilepsy. To date no study has investigated a
      wide range of neuropsychiatric symptoms in right AHE outpatients. PATIENTS AND
      METHODS: Three patients with right AHE participated in this study. The control
      group are patients with cognitive complaints with no history of epilepsy or
      neurological impairment and no structural abnormalities on the MRI/CT. We
      expected no difference in verbal memory compared to the controls. Concerning
      affective Theory of Mind (ToM) we expect a difference between controls and AHE
      patients. In terms of behavior it is expected that coping and behavioral
      questionnaires do not significantly differ between AHE and controls, but that
      proxies of AHE patients do report more behavioral/psychiatric symptoms. RESULTS:
      No significant difference was found between groups concerning the cognitive
      functions. For affective ToM we did find a significant difference (p=0.044). A
      significant difference for the use of more reassuring thoughts (p=0.006) and a
      trend for less passive reactions on the coping questionnaire, suggesting an
      'active coping style'. Overall, AHE patients report fewer problems the self-
      reported questionnaires. Proxies of the AHE patients reported a trend for more
      behavioral disinhibition compared to proxy ratings of the control group.
      CONCLUSION: Right AHE patients underestimate their behavioral and emotional
      changes due to self-awareness deficits. Ratings of significant others are of
      immense importance for the detection of psychiatric and behavioral problems.
      Lesions in the amygdala- orbitofrontal cortex connection disrupt the emotional
      network, which might explain our results.

PMID- 29175725
TI  - Estimation of the number of contributors of theoretical mixture profiles based on
      allele counting: Does increasing the number of loci increase success rate of
      estimates?
AB  - DNA mixtures are more frequently encountered in casework due to increased kit
      sensitivity, protocols with increased cycle number, and requests for low copy
      number DNA samples to be tested. Generally, the first step in mixture
      interpretation is determining the number of contributors, with the most common
      approach of maximum allele count. Although there are previous studies regarding
      the accuracy of this approach, none have evaluated the accuracy with the newly
      expanded U.S. core STR loci. In this work, 4,976,355 theoretical mixture
      combinations were generated with the PowerPlex(r) Fusion 6C system which includes
      23 autosomal STR loci and three Y-STR loci. The number of contributors could be
      correctly assumed for 100% two-person and 99.99% three-person mixtures, whereas,
      four-, five-, and six-person mixtures were correctly assumed in 89.7%, 57.3%, and
      7.8% of mixtures, respectively. Y-STR analysis showed the 3 Y-STR markers are
      only accurate for two-person male mixtures (96.7%). This work demonstrates that
      maximum allele count using the expanded U.S. core loci is not much improved from
      previous smaller panels, reiterating that this method is not as accurate beyond
      three contributors.

PMID- 29175726
TI  - The redesigned Forensic Research/Reference on Genetics-knowledge base, FROG-kb.
AB  - The Forensic Resource/Reference on Genetics-knowledge base (FROG-kb) web site
      <https://frog.med.yale.edu/FrogKB/> was introduced in 2011 and in the five years
      since the previous publication ongoing research into how the database can better
      serve forensics has resulted in extensive redesign of the database interface and
      functionality. Originally designed as a prototype to support forensic use of
      single nucleotide polymorphisms (SNPs), FROG-kb provides a freely accessible web
      interface that facilitates forensic practice and can be useful for teaching and
      research. Based on knowledge gained through its use, the web interface has been
      redesigned for easier navigation through the multiple components. The site also
      has functional enhancements, extensive new documentation, and new reference
      panels of SNPs with new curated data. FROG-kb focuses on single nucleotide
      polymorphisms (SNPs) and provides reference population data for several published
      panels of individual identification SNPs (IISNPs) and several published panels of
      ancestry inference SNPs (AISNPs). For each of the various marker panels with
      reference population data, FROG-kb calculates random match probabilities (RMP)
      and relative likelihoods of ancestry for a user-entered genotype profile (either
      completely or partially specified). Example genotype profiles are available and
      the User's Manual presents interpretation guidelines for the calculations. The
      extensive documentation along with ongoing updates makes FROG-kb a comprehensive
      tool in facilitating use of SNPs in forensic practice and education. An overview
      of the new FROG-kb with examples and material explaining the results of its use
      are presented here.

PMID- 29175727
TI  - A step towards a holistic assessment of soil degradation in Europe: Coupling on
      site erosion with sediment transfer and carbon fluxes.
AB  - Soil degradation due to erosion is connected to two serious environmental
      impacts: (i) on-site soil loss and (ii) off-site effects of sediment transfer
      through the landscape. The potential impact of soil erosion processes on
      biogeochemical cycles has received increasing attention in the last two decades.
      Properly designed modelling assumptions on effective soil loss are a key pre
      requisite to improve our understanding of the magnitude of nutrients that are
      mobilized through soil erosion and the resultant effects. The aim of this study
      is to quantify the potential spatial displacement and transport of soil sediments
      due to water erosion at European scale. We computed long-term averages of annual
      soil loss and deposition rates by means of the extensively tested spatially
      distributed WaTEM/SEDEM model. Our findings indicate that soil loss from Europe
      in the riverine systems is about 15% of the estimated gross on-site erosion. The
      estimated sediment yield totals 0.164 +/- 0.013Pgyr-1 (which corresponds to 4.62
      +/- 0.37Mgha-1yr-1 in the erosion area). The greatest amount of gross on-site
      erosion as well as soil loss to rivers occurs in the agricultural land (93.5%).
      By contrast, forestland and other semi-natural vegetation areas experience an
      overall surplus of sediments which is driven by a re-deposition of sediments
      eroded from agricultural land. Combining the predicted soil loss rates with the
      European soil organic carbon (SOC) stock, we estimate a SOC displacement by water
      erosion of 14.5Tg yr-1. The SOC potentially transferred to the riverine system
      equals to 2.2Tgyr-1 (~15%). Integrated sediment delivery-biogeochemical models
      need to answer the question on how carbon mineralization during detachment and
      transport might be balanced or even off-set by carbon sequestration due to
      dynamic replacement and sediment burial.

PMID- 29175728
TI  - On the contributions of photorespiration and compartmentation to the contrasting
      intramolecular 2H profiles of C3 and C4 plant sugars.
AB  - Compartmentation of C4 photosynthetic biochemistry into bundle sheath (BS) and
      mesophyll (M) cells, and photorespiration in C3 plants is predicted to have
      hydrogen isotopic consequences for metabolites at both molecular and site
      specific levels. Molecular-level evidence was recently reported (Zhou et al.,
      2016), but evidence at the site-specific level is still lacking. We propose that
      such evidence exists in the contrasting 2H distribution profiles of glucose
      samples from naturally grown C3, C4 and CAM plants: photorespiration contributes
      to the relative 2H enrichment in H5 and relative 2H depletion in H1 & H6 (the
      average of the two pro-chiral Hs and in particular H6,pro-R) in C3 glucose, while
      2H-enriched C3 mesophyll cellular (chloroplastic) water most likely contributes
      to the enrichment at H4; export of (transferable hydrogen atoms of) NADPH from C4
      mesophyll cells to bundle sheath cells (via the malate shuttle) and incorporation
      of 2H-relatively unenriched BS cellular water contribute to the relative
      depletion of H4 & H5 respectively; shuttling of triose-phosphates (PGA:
      phosphoglycerate dand DHAP: dihydroacetone phosphate) between C4 bundle sheath
      and mesophyll cells contributes to the relative enrichment in H1 & H6 (in
      particular H6,pro-R) in C4 glucose.

PMID- 29175729
TI  - RNA regulons in cancer and inflammation.
AB  - Gene expression is the fundamental driving force that coordinates normal cellular
      processes and adapts to dysfunctional conditions such as oncogenic development
      and progression. While transcription is the basal process of gene expression, RNA
      transcripts are both the templates that encode proteins as well as perform
      functions that directly regulate diverse cellular processes. All levels of gene
      expression require coordination to optimize available resources, but how global
      gene expression drives cancers or responds to disrupting oncogenic mutations is
      not understood. Post-transcriptional coordination is controlled by RNA regulons
      that are governed by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs) that
      bind and regulate multiple overlapping groups of functionally related RNAs. RNA
      regulons have been demonstrated to affect many biological functions and diseases,
      and many examples are known to regulate protein production in cancer and immune
      cells. In this review, we discuss RNA regulons demonstrated to coordinate global
      post-transcriptional mechanisms in carcinogenesis and inflammation.

PMID- 29175730
TI  - Formation and function of tissue-resident memory T cells during viral infection.
AB  - Memory T cells are an important component of the adaptive immune response. Tissue
      resident memory T cells (TRM) are a recently described subset of memory T cells
      that reside in peripheral tissues and are maintained independently of circulating
      subsets of memory T cells. Importantly, TRM are frequently found in barrier
      tissues that commonly serve as entry portals for pathogens such as viruses.
      Mounting evidence shows that TRM are superior to their circulating counterparts
      in conferring protective immunity against a wide range of viruses. In this
      review, we will discuss the role of TRM in controlling viral infection with a
      focus on CD8+ TRM, the factors that regulate differentiation and a potential role
      for TRM in future vaccine development.

PMID- 29175731
TI  - Consequences of perinatal infections with rubella, measles, and mumps.
AB  - Measles, mumps, and rubella have recently taken the stage as re-emerging diseases
      of public health importance-particularly in regards to the consequences seen with
      perinatal infections. Effective vaccination strategies have successfully reduced
      the spread of measles, mumps, and rubella in the United States, but a current
      trend of increased vaccination hesitancy, fear of vaccine safety, and spread of
      misconceptions surrounding the science of vaccines have led to a relative
      resurgence of these diseases in the developed world. This article aims to explore
      why measles, mumps, and rubella should continue to be on the radar of medical
      professionals, and why the study of these diseases is important for understanding
      other teratogenic viruses of public health importance.

PMID- 29175732
TI  - The precision of predicting the time of onset of parturition in the bitch using
      the level of progesterone in plasma during the preparturient period.
AB  - Precise prediction of the time of onset of parturition in the bitch is of
      clinical importance. Many parturition management cases in clinical practice are
      presented in the last two weeks of pregnancy without a reliable estimate of the
      parturition date. The aim of this study was to assess the value of a single
      progesterone level in the blood plasma from a preparturient bitch to predict the
      time of onset of parturition. The temporal relationship between the decrease in
      the plasma progesterone levels and the time of cervical dilatation (TCD)-which
      correlates to the onset of stage 1 of parturition-was evaluated in 25 bitches in
      the preparturient period. Among bitches destined to reach TCD within 12 h there
      is a 2% probability of having a plasma progesterone level of 15.8 nmoL/L or above
      and a 6% probability of having a level of 8.7 nmoL/L or above. Conversely, if the
      level is below 8.7 nmoL/L there is a 99% probability of reaching TCD within 48 h
      and if the level is below 3.18 nmoL/L there is a 100% probability of reaching TCD
      within 24 h. These results allow the veterinary obstetrician to make prompt
      decisions in the management of parturition.

PMID- 29175733
TI  - Examining the role of attachment in the relationship between childhood adversity,
      psychological distress and subjective well-being.
AB  - Childhood adversity is associated with a wide range of detrimental psychological
      consequences. This study examined the mediating role of relationship-specific
      attachment (avoidance and anxiety) in the associations between childhood
      adversity and both psychological distress and subjective well-being. University
      students (N=190) across the Republic of Ireland completed self-report measures
      including the Adverse Childhood Experiences scale, Experiences in Close
      Relationships - Relationship Structures scale, Depression Anxiety and Stress
      scales and measures of subjective well-being. One hundred and twenty-eight
      participants (67.4%) reported experiencing at least one adverse childhood
      experience. Childhood adversity was associated with symptoms of psychological
      distress and subjective well-being. All such associations were mediated by
      certain relationship-specific attachment dimensions. Of these, attachment anxiety
      in general relationships was the most prominent mediator for both psychological
      distress and subjective well-being. Attachment to one's father and to one's
      romantic partner did not mediate any association. These findings indicate that
      attachment, in particular relationships, is an important factor in the
      associations between childhood adversity and both psychological distress and
      subjective well-being as an adult. One's attachment anxiety in general
      relationships is particularly important in these associations. Therapeutic
      interventions addressing these attachment domains may offset the detrimental
      effects of childhood adversity. Future research is required using a longitudinal
      design.

PMID- 29175734
TI  - Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and
      a prognostic biomarker for survival in metastatic melanoma patients.
AB  - INTRODUCTION: Tumour burden is a prognostic biomarker in metastatic melanoma.
      However, tumour burden is difficult to measure and there are currently no
      reliable surrogate biomarkers to easily and reliably determine it. The aim of
      this study was to assess the potential of plasma total cell free DNA as biomarker
      of tumour burden and prognosis in metastatic melanoma patients. MATERIALS AND
      METHODS: A prospective biomarker cohort study for total plasma circulating cell
      free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients.
      For 38 patients, paired blood collections and scan assessments were available
      before treatment and at first response evaluation. Tumour burden was calculated
      as the sum of volumes from three-dimensional radiological measurements of all
      metastatic lesions in individual patients. RESULTS: Baseline cfDNA concentration
      correlated with pre-treatment tumour burden (rho = 0.52, P < 0.001). Baseline
      cfDNA levels correlated significantly with hazard of death and overall survival,
      and a cut off value of 89 pg/MUl identified two distinct prognostic groups (HR =
      2.22 for high cfDNA, P = 0.004). Patients with cfDNA >=89 pg/MUl had shorter OS
      (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the
      significance was maintained when compared with lactic dehydrogenase (LDH) in a
      multivariate analysis. We also found a correlation between the changes of cfDNA
      and treatment-related changes in tumour burden (rho = 0.49, P = 0.002). In
      addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR =
      2.7 for cfDNA/tumour volume >=8 pg/(MUl*cm3), P = 0.024). CONCLUSIONS: We have
      demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic
      melanoma patients, and that it is prognostic for overall survival.

PMID- 29175736
TI  - Brain structural connectivity during adrenarche: Associations between hormone
      levels and white matter microstructure.
AB  - Levels of the adrenal hormones dehydroepiandrosterone (DHEA), its sulfate
      (DHEAS), and testosterone, have all been linked to behavior and mental health
      during adrenarche, and preclinical studies suggest that these hormones influence
      brain development. However, little is known about how variation in these hormones
      is associated with white matter structure during this period of life. The current
      study aimed to examine associations between DHEA, DHEAS, and testosterone, and
      white matter microstructure during adrenarche. To avoid the confounding effect of
      age on hormone levels, we tested these associations in 87 children within a
      narrow age range (mean age 9.56 years, SD=0.34) but varying in hormone levels.
      All children provided saliva samples directly after waking and completed a
      diffusion-weighted MRI scan. Higher levels of DHEA were associated with higher
      mean diffusivity (MD) in a widespread cluster of white matter tracts, which was
      partially explained by higher radial diffusivity (RD) and partially by higher
      axial diffusivity (AD). In addition, there was an interaction between DHEA and
      testosterone, with higher levels of testosterone being associated with higher
      fractional anisotropy (FA) and lower MD and RD when DHEA levels were relatively
      high, but with lower FA and higher MD and RD when DHEA levels were low. These
      findings suggest that relatively early exposure to DHEA, as well as an imbalance
      between the adrenal hormones, may be associated with alterations in white matter
      microstructure. These findings highlight the potential relevance of adrenarcheal
      hormones for structural brain development.

PMID- 29175735
TI  - Prognostic impact of interval breast cancer detection in women with pT1a N0M0
      breast cancer with HER2-positive status: Results from a multicentre population
      based cancer registry study.
AB  - BACKGROUND: Although human epidermal growth factor receptor 2 (HER2)
      overexpression is associated with poor prognosis, patients (pts) with pT1a N0M0
      breast cancers (BCs) have an excellent outcome across all subtypes. Interval
      cancers (ICs) have poorer survival than screen-detected (SD) tumours, and an
      association has been reported between ICs and HER2 overexpression. We aimed to
      determine, in a general population of pT1a N0M0 BCs with known screening status,
      whether HER2-positive ICs have a poorer outcome than HER2-positive SD cancers.
      METHODS: We evaluated all incident pT1a N0M0 BCs (n = 874) collected in the
      Emilia-Romagna region (Italy) from 2003 to 2009 and diagnosed in women aged 50
      69. Pts unexposed to screening, with unknown HER2 status and/or treated with
      adjuvant trastuzumab were excluded from analysis. RESULTS: Sixty-one percent of
      the BCs were SD, whereas 19% were ICs. BCs with high histologic grade, hormone
      receptor-negative or HER2-positive status (odds ratio=1.7; 95% confidence
      interval [CI]: 1.1-2.7) were more likely ICs. Median follow-up was 115 months.
      The 10-year invasive disease-free survival (iDFS) for HER2-positive ICs was lower
      than that for HER2-positive SD cancers: 75.0% (95% CI: 55.5%-94.5%) versus 93.8%
      (95% CI: 86.5%-100%). An interaction between ICs and HER2-positive status was
      found for poorer iDFS after adjusting for prognostic variables (HR = 5.3; 95% CI:
      1.6-16.7). CONCLUSIONS: IC detection may identify pts with HER2-positive pT1a
      N0M0 tumours in whom the rate of recurrence justifies consideration for
      conventional, anti-HER2, adjuvant treatment.

PMID- 29175737
TI  - Contrastive study on porphyrinic iron metal-organic framework supported on
      various carbon matrices as efficient electrocatalysts.
AB  - Porphyrinic iron metal-organic framework (pFeMOF) was combined with different
      kinds of carbon matrices, including porous graphene (PG), ordered mesoporous
      carbon (OMC) and macroporous carbon (MPC) via a simple one-step hydrothermal
      method. The introduction of carbon substrates improves the electrical
      conductivity and stability of pFeMOF. The presence of carbon also reduces the
      size of pFeMOF crystallites, leading to more active sites. The catalysts were
      used to electrocatalysis of hydrogen evolution reaction (HER) and the reduction
      of hydrogen peroxide (H2O2). Electrochemical measurements show that pFeMOF/PG has
      better electrocatalytic efficiency than pFeMOF/OMC, pFeMOF/MPC and pFeMOF. The
      HER on pFeMOF/PG displays a small onset potential of -34.37 mV vs. reversible
      hydrogen electrode (RHE), a low Tafel slope of 73.06 mV dec-1, a small over
      potential of 154.71 mV at 10 mA cm-2. The catalytic effect for H2O2 is also
      satisfied. The linearity range of H2O2 is as wide as 5-4310 MUM, and the
      sensitivity is as high as 77.38 MUA mM-1. Such splendid performances may be
      attributed to the crumpled structure of PG leading to evenly and smaller pFeMOF.
      Furthermore, abundant hierarchical pores of pFeMOF/PG result in larger
      electrochemically surface areas. Our work may provide a new approach to design
      efficient non-precious metal catalysts.

PMID- 29175738
TI  - Hierarchical hollow MnO2 nanofibers with enhanced supercapacitor performance.
AB  - One dimensional (1D) hollow nanostructures have been considered as one of the
      most fascinating materials for supercapacitors. Herein, the hollow MnO2
      nanofibers are successfully synthesized through a two-step process, in which the
      electrospun carbon nanofibers acted as sacrificial template. The resulting hollow
      nanofibers are composed of ultrathin MnO2 nanosheets, which can offer rich
      electrochemical active sites for electrochemical reactions. Importantly, the open
      and free interspaces among these ultrathin MnO2 nanosheets can significantly
      enhance the utilization of the active material even at high current density. Such
      unique hollow nanostructure endow the hollow MnO2 nanofibers electrode better
      electrochemical performance with specific capacitance of 291 F/g at 1 A/g,
      superior rate capability of ~73% (from 1 to 10 A/g), and excellent cycling
      stability of 90.9% retention after 5000 cycles, demonstrating the potential for
      practical application in energy storage devices.

PMID- 29175740
TI  - Attachment of Pt nanoparticles to a metal oxide surface using a thiol-carboxyl
      bifunctional molecule.
AB  - HYPOTHESIS: Molecular attachments to platinum have received far less study than
      binding to gold. Of particular interest is whether the binding of bifunctional
      molecules, containing both thiol and carboxyl groups, can attach platinum to
      surfaces such as metal oxides. EXPERIMENTS: Attachment of 4-mercaptobenzoic acid
      (4-MBA) to bulk and nanoparticulate platinum was studied by cyclic voltammetry
      (CV), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). Platinum
      nanoparticles were attached to TiO2 using 4-MBA and probed for Pt loading and
      electrocatalytic activity. FINDINGS: Currents for reduction and oxidation of a
      standard redox couple on a Pt wire are sharply decreased when the Pt is
      previously exposed to 4-MBA, indicating bonding. This effect is not observed for
      benzoic acid. The absence of the SH stretching vibrational mode in Raman spectra
      of 4-MBA-modified Pt nanoparticles is consistent with sulfur-bonding of the
      molecules to the nanoparticle surface. High-resolution XPS studies of S and Pt
      core electrons show the formation of SPt bonds. Therefore, 4-MBA binds to Pt via
      the S atom but not via the carboxyl group, enabling Pt attachment to other
      surfaces such as metal oxides. 4-MBA increased both the amount of Pt bound to a
      TiO2 surface and the rate of a redox reaction on the surface.

PMID- 29175739
TI  - One-pot aqueous fabrication of reduced graphene oxide supported porous PtAg alloy
      nanoflowers to greatly boost catalytic performances for oxygen reduction and
      hydrogen evolution.
AB  - Herein, reduced graphene oxide supported porous PtAg alloy nanoflowers (PtAg
      NFs/rGO) were synthesized by a simple one-pot aqueous method using pyridinium
      based dicationic ionic liquid (1,4-bis(pyridinium)butane dibromide, Bpb-2Br) as
      the new structure-director and stabilizing agent. The products were characterized
      by a series of techniques. The obtained nanocomposite had more positive onset
      potential (1.03 V) for oxygen reduction reaction (ORR) in alkaline electrolyte
      than those of commercial Pt/C (50 wt%, 0.96 V) and home-made Pt nanoparticles
      (NPs)/rGO (Pt NPs/rGO, 0.97 V), showing the enhanced catalytic performance for
      hydrogen evolution reaction (HER) with the positive onset potential (-26 mV) and
      a small Tafel slope (31 mV dec-1) relative to Pt/C (-18 mV, 31 mV dec-1) and Pt
      NPs/rGO (-42 mV, 36 mV dec-1) in 0.5 M H2SO4.

PMID- 29175741
TI  - Responsive complex capsules prepared with polymerization of dopamine, hydrogen
      bonding assembly, and catechol dismutation.
AB  - Complex capsules were fabricated by combining the polymerization of dopamine with
      hydrogen-bonding layer-by-layer assembly (LbL) of dopamine-modified poly(acrylic
      acid) (PAA-dopa) and poly(vinylpyrrolidone) (PVPON). PDA(PAA-dopa/PVPON)n shell
      was cross-linked by dismutation reaction among catechol groups of polydopamine
      (PDA) and PAA-dopa. During LbL assembly, PAA-dopa and PVPON diffuse in the robust
      PDA pre-layer, and hence the complex capsules become soft and flexible. With the
      change of environmental pH value, the hydrogen bonds in PDA(PAA-dopa/PVPON)n
      capsules would dissociate or reconstruct, and thus the complex capsules exhibit
      pH-responsive swelling-shrinking behavior. With only one assembled bilayer,
      PDA(PAA-dopa/PVPON)1 capsules show a volume swelling ratio of 1.34 from pH 2.0 to
      pH 8.5. In addition, the complex capsules display controlled loading and release
      of Rhodamine 6G (R6G) as pH value changed, which can be considered as a potential
      candidate for drug delivery.

PMID- 29175742
TI  - Facile hydrothermal synthesis of carbon-coated cobalt ferrite spherical
      nanoparticles as a potential negative electrode for flexible supercapattery.
AB  - Battery type electrodes would replace the currently available pseudocapacitive
      electrodes by the cause of high energy density and long discharge time. In this
      regard, battery type carbon coated CoFe2O4 spherical nanoparticles is prepared by
      the facile hydrothermal method and tested as the possible negative electrode for
      supercapattery applications. The phase purity, electronic states of elements, and
      the presence of carbon is inferred through various sophisticated techniques. The
      calculated surface area of CoFe2O4 and carbon coated CoFe2O4 are found to be 9
      and 26 m2 g-1, respectively. The morphological analysis confirms the formation of
      uniform CoFe2O4 nanospheres (~25 nm) with a thin layer of carbon coating (~2 nm).
      The amorphous carbon coating over CoFe2O4 nanosphere is identified via high
      resolution transmission electron microscope. The observed peak and plateau
      regions in the cyclic voltammogram and galvanostatic charge/discharge curves
      reveals the battery-type charge storage behaviour of the material. The carbon
      coated CoFe2O4 delivers the maximum length capacitance of 9.9 F m-1 at 1 mV s-1
      with a useful lifespan over 5000 cycles. The electrochemical impedance
      spectroscopy reveals that the carbon-coated CoFe2O4 delivers the low charge
      transfer resistance than CoFe2O4. Further, the fabricated supercapattery provides
      the energy density of 160 * 10-8 Wh cm-1 at a power density of 67.2 MUW cm-1. As
      well as, the device shows 93% of coulombic efficiency and 75% of the specific
      capacitance retention over 11,000 cycles. Overall, it is believed that the carbon
      coated CoFe2O4 can serve as a good candidate for flexible supercapatteries.

PMID- 29175743
TI  - Metabolomics and transcriptomics reveal the toxicity of difenoconazole to the
      early life stages of zebrafish (Danio rerio).
AB  - Difenoconazole is widely used to inhibit the growth of fungi, but its residue in
      the water environment may threaten ecosystem and human health. Here, 1H nuclear
      magnetic resonance (NMR) and LC-MS/MS based metabolomics and transcriptomics
      approaches were used to assess the response of zebrafish to difenoconazole
      exposure. Early life stages of zebrafish were exposed to difenoconazole at
      environmentally relevant concentrations for 168h. Their comparison with the
      control group suggested an adverse development and disturbance of steroid
      hormones and VTG. KEGG pathway analysis identified five biological processes on
      the basis of differentially expressed genes (DEGs), as well as altered
      metabolites and amino acids in zebrafish following difenoconazole exposure. These
      affected processes included energy metabolism, amino acids metabolism, lipid
      metabolism, nucleotide metabolism, and an immune-related pathway. Collectively,
      these results bring us closer to an incremental understanding of the toxic
      effects of difenoconazole on zebrafish in its early development, and lend support
      to the continued use of the early life stages of zebrafish as a classical model
      to evaluate underlying environmental risks of xenobiotics in aquatic organisms.

PMID- 29175744
TI  - Third-rank chromatic aberrations of electron lenses.
AB  - In this paper the third-rank chromatic aberration coefficients of round electron
      lenses are analytically derived and numerically calculated by Mathematica.
      Furthermore, the numerical results are cross-checked by the differential
      algebraic (DA) method, which verifies that all the formulas for the third-rank
      chromatic aberration coefficients are completely correct. It is hoped that this
      work would be helpful for further chromatic aberration correction in electron
      microscopy.

PMID- 29175745
TI  - Dynamical scattering image simulations for two-phase gamma-gamma'
      microstructures: A theoretical model.
AB  - We introduce an extension of the Darwin-Howie-Whelan (DHW) equations for the case
      of coherent L12 precipitates in an FCC matrix. The equations are similar in form
      to the conventional DHW equations and are sufficiently general to account for the
      different translational variants of the precipitate phase as well as for the
      displacement fields of arbitrary lattice defects. An approximate scheme to
      perform fast and accurate image simulations using a pre-computed list of
      scattering matrices is also introduced. Finally, the results of diffraction
      pattern and image simulations are shown for two synthetic microstructures for a
      Ni-Al alloy generated using phase field simulations. The dynamical scattering
      equations reveal that the precipitate phase superlattice beams can propagate
      through the disordered matrix, but they are fully decoupled from the fundamental
      waves.

PMID- 29175746
TI  - DNA barcoding in concentrated Chinese medicine granules using adaptor ligation
      mediated polymerase chain reaction.
AB  - The use of DNA barcodes for species identification is a common laboratory
      practice. However, PCR amplification of full-length DNA barcode in processed
      material is difficult because of severe DNA fragmentation. In this study, an
      adaptor ligation-mediated PCR protocol was derived to amplify sets of target DNA
      fragments isolated from two CCMG products. The specially designed adaptor with
      asymmetric strands and terminal modification avoids amplification of non-target
      DNA sequences. DNA extracted from Angelica sinensis and Panax notoginseng CCMG
      were ligated with the adaptors and amplified by an adaptor primer and a single
      universal barcode primer to obtain partial ITS2 sequence. Results showed that
      various length of DNA fragments within the ITS2 region were amplified and could
      be used to identify the concerned species. The adaptor ligation-mediated PCR is
      therefore a promising universal method for species identification in highly
      processed herbal products.

PMID- 29175747
TI  - Development and validation of a new HPLC-MS method for meglumine impurity
      profiling.
AB  - We report a new High Performance Liquid Chromatography-Mass Spectrometry (HPLC
      MS) method to rapidly detect and quantify meglumine by-products (specifically
      reducing sugar(s) and nitrogen impurities) that could be present in the meglumine
      samples. Meglumine is a secondary amine obtained from glucose and it is an
      excipient used as counter-ion in several pharmaceutical formulations, especially
      when the concentration of the active pharmaceutical ingredient (API) is so high
      that the sodium is not a suitable option. Moreover, the increased use of
      meglumine is related to its ability to improve solubility in aqueous solutions
      due to the presence of a large number of hydroxyl groups. Thus, even if meglumine
      is widely used as excipient in pharmaceutical formulations, its impurity profile
      has never been fully evaluated. Here, we propose the use of a commercial agent
      that specifically reacts with carbonyl compounds, 1-(4-aminobenzyl)-1,2,4
      triazole, with the aim of improving the detection of reducing sugars, such as
      glucose, after an easy derivatization procedure. Finally, we describe the method
      validation and the analysis of the impurity profile of meglumine samples from
      different manufacturers.

PMID- 29175748
TI  - The reason leading to the increase of icariin in Herba Epimedii by heating
      process.
AB  - Icariin (ICA), a major flavonoid responsible for the pharmacological actions of
      Herba Epimedii, was found to be increased significantly after the heating
      process. The increase of ICA was considered to be due to the transformation of
      other flavonoids, in particular, epimedin (EPI) A-C. This novel study
      demonstrated that the increase of ICA in Epimedium. koreanum was induced mainly
      through the conversion of 3'''-carbonyl-2''-beta-l-quinovosyl icariin (CQICA) by
      deglycosylation during the heating process. Furthermore, the comparative analysis
      of the changes of CQICA and ICA in four raw Epimedium species (EPs) designated in
      the Chinese Pharmacopoeia revealed that the increase of ICA during the heating
      process was associated with the presence of CQICA in EPs. The present study
      provided scientific evidence for the conversion of CQICA into ICA, correcting the
      understanding of the transformation of EPI A-C into ICA. The results provided a
      reasonable scientific basis for the traditional use of processed Herba Epimedii,
      and might be helpful for the quality assessment of EPs.

PMID- 29175749
TI  - The effectiveness of Baby-CIMT in infants younger than 12 months with clinical
      signs of unilateral-cerebral palsy; an explorative study with randomized design.
AB  - AIM: To explore the effectiveness of baby-CIMT (constraint-induced movement
      therapy) and baby-massage for improving the manual ability of infants younger
      than 12 months with unilateral cerebral palsy (CP). METHOD: Infants eligible for
      inclusion were 3-8 months old with asymmetric hand function and at high risk of
      developing unilateral CP. Thirty-seven infants were assigned randomly to receive
      baby-CIMT or baby-massage. At one year of age 31 children were diagnosed with
      unilateral CP, 18 (8 boys, 6.1+/-1.7months) of these had received baby-CIMT and
      13 (8 boys, 5.0+/-1.6months) baby-massage. There were two 6-week training periods
      separated by a 6-week pause. The Hand Assessment for Infants (HAI), Assisting
      Hand Assessment (AHA), the Parenting Sense of Competence Scale (PSCS) and a
      questionnaire concerning feasibility were applied. RESULTS: There was improvement
      in the "Affected hand score" of HAI from median 10 (6;13 IQR) to 13 (7;17 IQR)
      raw score in the baby-CIMT group and from 5 (4;11 IQR) to 6 (3;12 IQR) for baby
      massage with a significant between group difference (p=0.041). At 18-month of
      age, the median AHA score were 51 (38;72 IQR) after baby-CIMT (n=18) compared to
      24 (19;43 IQR) baby-massage (n=9). The PSCS revealed an enhanced sense of
      competence of being a parent among fathers in the baby-CIMT group compared to
      fathers in the baby-massage (p=0.002). Parents considered both interventions to
      be feasible. CONCLUSION: Baby-CIMT appears to improve the unimanual ability of
      young children with unilateral CP more than massage.

PMID- 29175750
TI  - Incidence of lower-extremity muscle weakness after quadratus lumborum block.

PMID- 29175751
TI  - Lidocaine post-nasal dripping (LPND): An easy way for awake nasal intubation.

PMID- 29175752
TI  - Lack of generalizability of observational studies' findings for turnover time
      reduction and growth in surgery based on the State of Iowa, where from one year
      to the next, most growth was attributable to surgeons performing only a few cases
      per week.
AB  - STUDY OBJECTIVE: Three observational studies at large teaching hospitals found
      that reducing turnover times resulted in the surgeons performing more cases. We
      sought to determine if these findings are generalizable to other hospitals,
      because, if so, reducing turnover times may be an important mechanism for
      hospitals to use for growing caseloads. DESIGN: Observational cohort study.
      SETTING: 116 hospitals in Iowa with inpatient or outpatient surgery from July 1,
      2013 through June 30, 2015. SUBJECTS: Surgeons in Iowa, each with a unique
      identifier among hospitals. MEASUREMENTS: The independent variable was the number
      of inpatient and outpatient cases that each surgeon performed each week during
      the first fiscal year beginning July 1, 2013. The dependent variables were
      surgeons' number of inpatient and outpatient surgical cases, and intraoperative
      work relative value units (RVU's) for outpatient cases, during the second fiscal
      year. MAIN RESULTS: The average hospital in Iowa had less than half of its growth
      from year 1 to year 2 in numbers of cases among surgeons who performed >2 cases
      per week in the baseline year (23.0%+/-2.5% [SE], P<0.0001 comparing mean to
      50%). Less than half the growth in RVU's was among those surgeons (18.1%+/-2.2%,
      P<0.0001). The average hospital in Iowa had less than half of its growth in
      numbers of cases among surgeons who performed 2 or fewer cases per week at the
      hospital during the baseline year and >2 cases per week at other hospitals in the
      state during that year (24.4%+/-2.6%, P<0.0001). Less than half the growth in
      RVU's was among those surgeons (21.3%+/-2.5%, P<0.0001). CONCLUSIONS: Most
      (>=50%) annual growth in surgery, both based on the number of total inpatient and
      outpatient surgical cases, and on the total outpatient RVU's, was attributable to
      surgeons who performed 2 or fewer cases per week at each hospital statewide
      during the preceding year. Therefore, the strategic priority should be to assure
      that the many low-caseload surgeons have access to convenient OR time (e.g., by
      allocating sufficient OR time, and assigning surgeon blocks, in a mathematically
      sound, evidence-based way). Although reducing turnover times and anesthesia
      controlled times to promote growth will be beneficial for a few surgeons, the
      effect on total caseload will be small.

PMID- 29175756
TI  - Shared identity in organizational stress and change.
AB  - The social identity approach has been found very useful for the understanding of
      a range of phenomena within and across organizations. It has been applied in
      particular to analyze employees' stress and well-being at work and their
      reactions to organizational change. In this paper, we argue that there is a
      mismatch between the theoretical notion of shared identities in teams and
      organizations and empirical research, which largely focuses on the individual
      employee's identification with his or her social categories at work. We briefly
      review the literature in the two areas of stress and change and conclude with an
      agenda for future research.

PMID- 29175753
TI  - Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and
      migration by suppressing ROS/NFkappaB/mTOR/P70S6K signaling cascade.
AB  - Phenotypic switch of vascular smooth muscle cells (VSMCs) is characterized by
      increased expressions of VSMC synthetic markers and decreased levels of VSMC
      contractile markers, which is an important step for VSMC proliferation and
      migration during the development and progression of cardiovascular diseases
      including atherosclerosis. Chicoric acid (CA) is identified to exert powerful
      cardiovascular protective effects. However, little is known about the effects of
      CA on VSMC biology. Herein, in cultured VSMCs, we showed that pretreatment with
      CA dose-dependently suppressed platelet-derived growth factor type BB (PDGF-BB)
      induced VSMC phenotypic alteration, proliferation and migration. Mechanistically,
      PDGF-BB-treated VSMCs exhibited higher mammalian target of rapamycin (mTOR) and
      P70S6K phosphorylation, which was attenuated by CA pretreatment,
      diphenyleneiodonium chloride (DPI), reactive oxygen species (ROS) scavenger N
      acetyl-l-cysteine (NAC) and nuclear factor-kappaB (NFkappaB) inhibitor Bay117082.
      PDGF-BB-triggered ROS production and p65-NFkappaB activation were inhibited by
      CA. In addition, both NAC and DPI abolished PDGF-BB-evoked p65-NFkappaB nuclear
      translocation, phosphorylation and degradation of Inhibitor kappaBalpha
      (IkappaBalpha). Of note, blockade of ROS/NFkappaB/mTOR/P70S6K signaling cascade
      prevented PDGF-BB-evoked VSMC phenotypic transformation, proliferation and
      migration. CA treatment prevented intimal hyperplasia and vascular remodeling in
      rat models of carotid artery ligation in vivo. These results suggest that CA
      impedes PDGF-BB-induced VSMC phenotypic switching, proliferation, migration and
      neointima formation via inhibition of ROS/NFkappaB/mTOR/P70S6K signaling cascade.

PMID- 29175755
TI  - Catalytic efficiency is a better predictor of arsenic toxicity to soil alkaline
      phosphatase.
AB  - Arsenic (As) is an inhibitor of phosphatase, however, in the complex soil system,
      the substrate concentration effect and the mechanism of As inhibition of soil
      alkaline phosphatase (ALP) and its kinetics has not been adequately studied. In
      this work, we investigated soil ALP activity in response to As pollution at
      different substrate concentrations in various types of soils and explored the
      inhibition mechanism using the enzyme kinetics. The results showed that As
      inhibition of soil ALP activity was substrate concentration-dependent. Increasing
      substrate concentration decreased inhibition rate, suggesting reduced toxicity.
      This dependency was due to the competitive inhibition mechanism of As to soil
      ALP. The kinetic parameters, maximum reaction velocity (Vmax) and Michaelis
      constant (Km) in unpolluted soils were 0.012-0.267mMh-1 and 1.34-3.79mM
      respectively. The competitive inhibition constant (Kic) was 0.17-0.70mM, which
      was lower than Km, suggesting higher enzyme affinity for As than for substrate.
      The ecological doses, ED10 and ED50 (concentration of As that results in 10% and
      50% inhibition on enzyme parameter) for inhibition of catalytic efficiency
      (Vmax/Km) were lower than those for inhibition of enzyme activity at different
      substrate concentrations. This suggests that the integrated kinetic parameter,
      catalytic efficiency is substrate concentration independent and more sensitive to
      As than ALP activity. Thus, catalytic efficiency was proposed as a more reliable
      indicator than ALP activity for risk assessment of As pollution.

PMID- 29175754
TI  - 8-Oxoguanine DNA glycosylase 1: Beyond repair of the oxidatively modified base
      lesions.
AB  - Oxidative stress and the resulting damage to genomic DNA are inevitable
      consequences of endogenous physiological processes, and they are amplified by
      cellular responses to environmental exposures. One of the most frequent reactions
      of reactive oxygen species with DNA is the oxidation of guanine to pre-mutagenic
      8-oxo-7,8-dihydroguanine (8-oxoG). Despite the vulnerability of guanine to
      oxidation, vertebrate genes are primarily embedded in GC-rich genomic regions,
      and over 72% of the promoters of human genes belong to a class with a high GC
      content. In the promoter, 8-oxoG may serve as an epigenetic mark, and when
      complexed with the oxidatively inactivated repair enzyme 8-oxoguanine DNA
      glycosylase 1, provide a platform for the coordination of the initial steps of
      DNA repair and the assembly of the transcriptional machinery to launch the prompt
      and preferential expression of redox-regulated genes. Deviations/variations from
      this artful coordination may be the etiological links between guanine oxidation
      and various cellular pathologies and diseases during ageing processes.

PMID- 29175757
TI  - Identification and characterization of chemosensory gene families in the bark
      beetle, Tomicus yunnanensis.
AB  - The bark beetle, Tomicus yunnanensis (Coleoptera: Scolytinae), is a seriously
      destructive pest of Yunnan pine (Pinus yunnanensis) and is distributed solely in
      Southwestern China. It has been a challenge to control this pest owing to its
      resistance to chemical pesticides, which have been used as the main control
      strategy of this species in recent years. Since this approach will continue until
      an alternative mitigation strategy is implemented, it is essential to develop
      novel or improved biocontrol approaches. In the current study, we aimed to
      identify most, if not all, of the bark beetle's chemosensory genes, and to
      address their respective phylogenetic relationships and expression
      characteristics. Digital gene expression (DGE) profiling and a comparison of the
      profiles at three developmental stages yielded 40,287,265 clean reads and a large
      number of differentially expressed genes (DEGs), with 21 up- and 20 down
      regulated DEGs involved in chemoreception. Transcriptome of the three mixed
      stages revealed a total of 80 transcripts encoding chemosensory-related proteins
      comprising 45 odorant-binding proteins (OBPs), 12 chemosensory proteins (CSPs),
      20 receptor proteins [9 odorant receptors (ORs), 8 gustatory receptors (GRs) and
      3 ionotropic receptors (IRs)] and 3 sensory neuron membrane proteins (SNMPs). As
      many as 38 full-length sequences were acquired with a combination of
      transcriptomic analysis and rapid amplification of cDNA ends (RACE) strategy.
      Phylogenetic analysis showed that T. yunnanensis OBPs were clustered into four
      sub-groups: 27 Minus-C OBPs, 5 antennal binding proteins (ABPIIs), 10 Classic
      OBPs and one Plus-C OBP; meanwhile, the ORs were grouped into four clades (1, 2,
      7b and Orco). Expression profiles revealed that 66 of 80 genes were detected in
      the three DGE libraries, and 15 soluble olfactory proteins were antennae
      predominant, possibly guiding olfactory-associated behaviors of this beetle.
      Taken together, our study has provided valuable data for further functional
      studies of this beetle and will facilitate the identification of potential
      molecular targets associated with chemosensory reception for use in biocontrol
      strategies.

PMID- 29175758
TI  - Photoprotective potential of metabolites isolated from algae-associated fungi
      Annulohypoxylon stygium.
AB  - Natural products, or secondary metabolites, obtained from fungal species
      associated with marine algae have been widely used in sunscreens due to their
      antioxidant activity and protective potential against solar radiation. The
      endophytic fungus isolated from Bostrychia radicans algae collected in the Rio
      Escuro mangrove, Sao Paulo State, Brazil, Annulohypoxylon stygium (Xylariaceae
      family) was studied to evaluate the photoprotective potential of its metabolites.
      The Annulohypoxylon genus can produce secondary metabolites with interesting
      cytotoxic, antibacterial and antioxidant properties and was never isolated before
      from a marine alga or had its metabolites studied for UV protection. The fungal
      culture (code As) extracted with dichloromethane: methanol (2:1) yielded 9
      fractions (Asa to Asi) which were submitted to different chromatographic
      methodologies to obtain pure compounds, and to spectroscopic methodologies to
      elucidate their structures. Also, a screening was conducted to evaluate the
      qualitative production of the metabolites, besides the absorption in the UVA/UVB
      range, their photostability and phototoxicity potential using the 3T3 NRU
      phototoxicity test (OECD TG 432). This study led to the isolation of a novel
      compound, 3-benzylidene-2-methylhexahydropyrrolo [1,2-alpha] pyrazine-1,4-dione
      (1), from fractions Ase3 and Asf3; Ase1 was identified as 1-(1,3-Benzodioxol-5
      yl)-1,2-propanediol (2), two metabolites were isolated as diastereomers (1S,2R)-1
      phenyl-1,2-propanediol (3) from Asd2 and (1R,2R)-1-phenyl-1,2-propanediol (4)
      from Asd3, and Ase1 and 1,3-benzodioxole-5-methanol (5) from Asc1. The results
      obtained showed a great potential source of new molecules to be used as UVB
      filters in sunscreens, since substances 1-2 presented UVB absorption, had no
      phototoxic potential and were considered photostable. In conclusion, these
      compounds can be considered as a potential new class of molecules for
      photoprotection, since their photosafety and non-cytotoxicity were predicted
      using in vitro methods for topical use. Meanwhile, further efficacy assays shall
      be conducted for the establishment of their Sun Protection Factor (SPF). Also,
      this work provided new information concerning the metabolic profile of A.
      stygium, since it was possible to obtain two enantiomer compounds (3) and (4).
      One of them belonged to the same skeleton, but with a methylenedioxy moiety,
      showing the richest enzymatic pattern for this microorganism.

PMID- 29175759
TI  - A membrane bioreactor with iron dosing and acidogenic co-fermentation for
      enhanced phosphorus removal and recovery in wastewater treatment.
AB  - A novel phosphorous (P) removal and recovery process using a membrane bioreactor
      (MBR) with ferric iron dosing and acidogenic co-fermentation was developed for
      municipal wastewater treatment. The very different solubility of Fe(III)-P and
      Fe(II)-P complex and the microbial transformation of Fe(III) to Fe(II) were
      utilized for P removal and recovery. By means of Fe-induced precipitation,
      chemical P removal was effectively achieved by an MBR with a flat-plate ceramic
      membrane; however, the Fe(III)-P solids accumulated in the MBR that constituted a
      significant fraction of the activated sludge. Anaerobic co-fermentation of the
      MBR sludge and food waste in a side-stream allowed the extraction of P and Fe
      from the sludge into the supernatant. The P in the supernatant was recovered as a
      fertilizer resource, while the sludge was returned to the MBR tank. The
      experimental results show that by adding FeCl3 at 20 mg Fe/L into the influent of
      domestic wastewater, about 95.6% of total P could be removed by the MBR. One
      fifth (20%) of the sludge in the MBR was circulated daily through the side-stream
      fermenters for co-fermentation with cooked rice as the model food waste. The
      sludge underwent acidogenesis and dissimilatory iron reduction, resulting in a
      drop of the pH to below 5.0 and reduction of Fe(III) to Fe(II). Owing to the high
      solubility of the Fe(II)-P complex, P and Fe were then dissolved and released
      from the sludge into the supernatant. By simply adjusting the solution pH to 8.0,
      the P and Fe(II) in the supernatant readily re-precipitated to form vivianite for
      the P recovery. Using the iron dosing MBR and side-stream sludge fermentation, an
      overall P recovery efficiency of 62.1% from wastewater influent can be achieved,
      and the problem of inorganic build-up in the MBR is effectively alleviated.

PMID- 29175760
TI  - Inventory, loading and discharge of synthetic phenolic antioxidants and their
      metabolites in wastewater treatment plants.
AB  - Little is known about the occurrence and fate of synthetic phenolic antioxidants
      (SPAs) and their metabolites in wastewater treatment plants (WWTPs). In this
      study, inventory, source, mass loading, and discharge of five SPAs, including 2,6
      di-tert-butyl-4-methylphenol (BHT) and four of its metabolites were examined,
      based on the concentrations determined in wastewater influent, primary effluent,
      final effluent, suspended particulate matter (SPM), and sludge collected from two
      WWTPs (denoted as WWTPA and WWTPB) in the Albany area of New York State. The
      respective median concentrations of sum of SPAs (SigmaSPAs = 6 compounds
      including metabolites) and SPA-metabolites (Sigmametabolites = 4 metabolites)
      were 2455-3330 and 290-465 ng/L in influents, and 1580-1604 and 511-822 ng/L in
      final effluents. Adsorption to sludge (SigmaSPAs ranged as 2420-4680 ng/g dry wt)
      accounted for ~1% of the SPA removal. The removal efficiency (RE) for BHT in
      WWTPs ranged between 62.3% and 76.2%, whereas negative REs were found for SPA
      metabolites ([-3020%]-[-65.6%]). WWTP-based mass loading of BHT accounted for ~4%
      10% of the total production volume reported in the USA, whereas ~1.0% of the
      annual production of BHT was discharged from WWTP through effluents. BHT present
      in personal care products was estimated to explain for >91% of the mass loading
      source into WWTPs.

PMID- 29175761
TI  - An improved protocol for extracting extracellular polymeric substances from
      granular filter media.
AB  - Extracellular polymeric substances (EPS) are an important parameter in drinking
      water biofilters, and, to date, this is the first study to compare protocols from
      the literature for extracting EPS from granular filter media. Five extraction
      protocols were compared, and one was improved by varying the type of initial
      physical treatment and the shaking intensity, temperature, and time of
      incubation. Extracting EPS from granular filter media in triplicate by combining
      2 g (wet weight) of filter media with 10 mL of extraction buffer (10 mM Tris, 10
      mM EDTA, 2.5% NaCl, pH 8), vortexing for 1 min, and incubating for 4 h at 35 
      degrees C with shaking at 200 rpm yielded significantly higher EPS polysaccharide
      and/or protein concentrations than did protocols from the literature. This
      improved protocol extracted a significant fraction of the biofilm attached to
      sand but was less effective on biofilm attached to anthracite or granular
      activated carbon (GAC). A survey of 11 full-scale biofilters from the U.S. and
      Canada revealed that EPS polysaccharide and protein concentrations can vary over
      one order of magnitude, from 0.02 to 0.60 mg glucose/g total solids (TS) and 0.27
      to 3.38 mg bovine serum albumin/g TS, respectively. Backwashing significantly
      lowered the biomass and EPS polysaccharide concentrations, but the majority of
      the biofilm remained attached to the filter media after backwashing, as expected.
      The fraction of EPS polysaccharides and proteins removed during backwashing did
      not differ between anthracite and GAC biofilters. The improved EPS extraction
      protocol can be utilized to investigate the role of EPS in biofilter performance.

PMID- 29175762
TI  - Chemical nanocavitation of surfaces to enhance the utility of stainless steel as
      a medical material.
AB  - While stainless steel is a broadly used alloy with interesting mechanical
      properties, its applications in medicine suffers from inherent biocompatibility
      limitations. An attractive opportunity to improve its performance is to alter its
      surface, but this has proven challenging. We now show how high range anodization
      conditions using H2SO4/H2O2 as an atypical electrolyte can efficiently
      nanocavitate the surface of both stainless steel SS304 and SS316 and create a
      topography with advantageous biomedical characteristics. We describe the
      structural and chemical features of the resulting surfaces, and propose a
      nanocorrosion/transpassivation/repassivation mechanism for its creation. Our
      approach creates a thin mesoporous layer of crystalline oxide that selectively
      promotes mammalian cell activity and limits bacterial adhesion. The modified
      surfaces favor the formation and maturation of focal adhesion plaques and
      environment-sensing filopodia with abundant extra small lateral membrane
      protrusions, suggesting an increase in membrane fluidity. These protrusions
      represent a yet undescribed cellular response. Such surfaces promise to
      facilitate the integration of implantable SS devices, in general. In addition,
      our strategy simultaneously provides a simple, commercially attractive way to
      control the adhesion of microorganisms, making nanostructured stainless steel
      broadly useful in hospital environments, in manufacturing medical devices, as
      well as offering possibilities for non-medical applications.

PMID- 29175763
TI  - Novel insights into microbial community dynamics during the fermentation of
      Central European ice wine.
AB  - Culture-dependent and culture-independent strategies were applied to investigate
      the microbiota of autumn undamaged and damaged berries, winter berries and ice
      wine must samples of Gruner Veltliner (Veltlinske zelene) from Small Carpathian
      wine-producing region. One hundred twenty-six yeasts and 242 bacterial strains
      isolated from several microbiological media (YPD, PDA, R2A, GYC, MRS and MRS-T)
      were clustered by ITS-PCR and subsequent Qiaxcel electrophoresis. Representatives
      of each cluster were identified by sequencing. The extracellular hydrolytic
      properties and intracellular activities of esterase and beta-glucosidase of
      isolates were assayed. The culture-independent approach permitted the analysis of
      extracted DNA and RNA coupling DGGE fingerprinting with construction of clone
      libraries (bacterial and fungal; DGGE-cloning). The combination of the two
      approaches provided comprehensive data that evidenced the presence of a complex
      microbiota in each analyzed sample. RNA and DNA analyses facilitated
      differentiation of living microorganisms from the entire microbiota. Diverse
      microbial communities colonized the autumn and winter berries. Generally, the
      combination of results obtained by the methods suggested that the must samples
      contained mainly Saccharomyces cerevisiae, Metschnikowia spp., Hanseniaspora
      uvarum, Lactococcus lactis and Leuconostoc spp. The strains exhibited interesting
      esterase and beta-glucosidase properties, which are important for aroma formation
      in wine. Fermentation strategies utilising these microorganisms, could be
      attempted in the future in order to modulate the ice wine characteristics.

PMID- 29175764
TI  - The effect of essential oils on microbial composition and quality of grass carp
      (Ctenopharyngodon idellus) fillets during chilled storage.
AB  - Antimicrobial and antioxidant effects of essential oils (oregano, thyme, and star
      anise) on microbial composition and quality of grass carp fillets were
      investigated. Essential oils treatment was found to be effective in inhibiting
      microbial growth, delaying lipid oxidation, and retarding the increase of TVB-N,
      putrescine, hypoxanthine, and K-value. Based on sensory analysis, shelf-life of
      grass carp fillets was 6days for control and 8days for treatment groups. Among
      the essential oils, oregano essential oil exhibited the highest antimicrobial and
      antioxidant activities. GC-MS analysis of essential oils components revealed that
      carvacrol (88.64%) was the major component of oregano essential oil. According to
      the results of high-throughput sequencing, Aeromonas, Glutamicibacter, and
      Aequorivita were the predominant microbiota in fresh control samples. However,
      oregano essential oil decreased the relative abundance of Aeromonas, while thyme
      and star anise essential oils decreased the relative abundance of Glutamicibacter
      and Aequorivita in fresh treated samples. The microbial composition of both
      control and treatment groups became less diverse as storage time increased.
      Aeromonas and Pseudomonas were dominant in spoiled samples and contributed to
      fish spoilage. Compared to the control, essential oils effectively inhibited the
      growth of Aeromonas and Shewanella in grass carp fillets during chilled storage.

PMID- 29175765
TI  - Consumer interest in environmental impact, safety, health and animal welfare
      aspects of modern pig production: Results of a cross-national choice experiment.
AB  - Are consumers interested in aspects of pig production and do they take these into
      account in their buying decisions when such information is available? Samples of
      consumers in Germany and Poland selected the two - for them - most important out
      of a list of ten production characteristics, relating to animal welfare, health
      and safety, and environmental issues. In a subsequent choice experiment, the
      relative weight these characteristics had in consumers' choices was estimated.
      Relative importance of production characteristics varied between consumer
      segments, with the production interested segment being bigger in Germany than in
      Poland. With the exception of one animal welfare related criterion in Germany,
      those production characteristics that consumers perceive as most important relate
      to health and safety aspects rather than to animal welfare and environmental
      impact.

PMID- 29175766
TI  - Estimation of pork quality in live pigs using biopsied muscle fibre number
      composition.
AB  - Here, we newly provided the parameters for estimating meat quality in live pigs
      using the muscle biopsy. The biopsied longissimus thoracis muscle was used to
      identify the muscle fibre characteristics (MFCs). Of the various MFCs in biopsied
      muscle, muscle fibre number (MFN) composition showed the greatest correlation
      with the MFCs in postmortem muscle (P<0.001). Moreover, the pigs cluster groups,
      based on the biopsied MFN composition, demonstrated statistically significant
      differences in meat quality traits such as muscle pH, drip loss, and meat colour
      (P<0.05). Therefore, we conclude that the MFN parameters in live pigs are closely
      related to the postmortem muscle metabolic rate and ultimately with the quality
      of meat. We suggest that the higher type I and lower type IIB MFN in biopsied
      muscle will result in better pork quality.

PMID- 29175768
TI  - Step-by-step manual for planning and performing bifurcation PCI: a resource
      tailored approach.
AB  - As bifurcation PCI can often be resource-demanding due to the use of multiple
      guidewires, balloons and stents, different technical options are sometimes being
      explored, in different local settings, to meet the need of optimally treating a
      patient with a bifurcation lesion, while being confronted with limited material
      resources. Therefore, it seems important to keep a proper balance between what is
      recognised as the contemporary state of the art, and what is known to be
      potentially harmful and to be discouraged. Ultimately, the resource-tailored
      approach to bifurcation PCI may be characterised by the notion of minimum
      technical requirements for each step of a successful procedure. Hence, this paper
      describes the logical sequence of steps when performing bifurcation PCI with
      provisional SB stenting, starting with basic anatomy assessment and ending with
      the optimisation of MB stenting and the evaluation of the potential need to stent
      the SB, suggesting, for each step, the minimum technical requirement for a
      successful intervention.

PMID- 29175769
TI  - Valve-in-valve transcatheter aortic valve implantation into a novel, sutureless
      bioprosthesis: technical considerations.

PMID- 29175767
TI  - Effects of noise overexposure on tone detection in noise in nonhuman primates.
AB  - This report explores the consequences of acoustic overexposures on hearing in
      noisy environments for two macaque monkeys trained to perform a reaction time
      detection task using a Go/No-Go lever release paradigm. Behavioral and non
      invasive physiological assessments were obtained before and after narrowband
      noise exposure. Physiological measurements showed elevated auditory brainstem
      response (ABR) thresholds and absent distortion product otoacoustic emissions
      (DPOAEs) post-exposure relative to pre-exposure. Audiograms revealed frequency
      specific increases in tone detection thresholds, with the greatest increases at
      the exposure band frequency and higher. Masked detection was affected in a
      similar frequency specific manner: threshold shift rates (change of masked
      threshold per dB increase in noise level) were lower than pre-exposure values at
      frequencies higher than the exposure band. Detection thresholds in sinusoidally
      amplitude modulated (SAM) noise post-exposure showed no difference from those in
      unmodulated noise, whereas pre-exposure masked detection thresholds were lower in
      the presence of SAM noise compared to unmodulated noise. These frequency
      dependent results were correlated with cochlear histopathological changes in
      monkeys that underwent similar noise exposure. These results reveal that
      behavioral and physiological effects of noise exposure in macaques are similar to
      those seen in humans and provide preliminary information on the relationship
      between noise exposure, cochlear pathology and perceptual changes in hearing
      within individual subjects.

PMID- 29175770
TI  - Catheter-based therapies in acute pulmonary embolism.
AB  - AIMS: To provide a systematic review of catheter-based therapies of acute
      pulmonary embolism. METHODS AND RESULTS: Studies published in peer-reviewed
      journals before February 2017 were included and categorized according to the
      mechanism of thrombus removal: fragmentation, rheolytic therapy, aspiration or
      catheter-directed thrombolysis. Strengths, challenges and the level of evidence
      of each device were evaluated. We found 16 different catheter-based therapies for
      acute PE; all but one being used off-label. The majority of procedures involve
      catheter-directed thrombolysis. Aspiration therapy shows promise, but limited
      data are available. Rheolytic therapy should be used with caution, if at all, due
      to the high number of associated complications. CONCLUSIONS: Catheter-based
      therapies show promise as a treatment for acute PE, though evidence is lacking.
      Further research into the efficacy and safety of devices is needed.

PMID- 29175771
TI  - Recovery of absolute coronary flow and resistance one week after percutaneous
      coronary intervention of a chronic totally occluded coronary artery using the
      novel RayFlow(c) infusion catheter.

PMID- 29175772
TI  - Antibacterial, anticandidal and antioxidant properties of Tanacetum argenteum
      (Lam.) Willd. subsp. flabellifolium (Boiss. & Heldr.) Grierson.
AB  - In the present study hydrodistilled essential oil and total methanol extracts of
      Tanacetum argenteum subsp. flabellifolium have been evaluated for their
      antimicrobial and antioxidant effects. The chemical composition of the oil and
      the crude extract were determined by GC/FID, GC/MS and LC/DAD/ESI-MS systems
      respectively. beta-thujone (47.1%), alpha-pinene (19.1%) and alpha-thujone
      (10.5%) were the main compounds of the essential oil while the 5-Ocaffeoylquinic
      acid, 1,5-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid were identified as
      flavonoid content of the crude extract. The oil and the methanol extract were
      demonstrated moderate antimicrobial effects (MIC range; 0,062-2,0 mg/mL) against
      21 different pathogenic micro organism. Total phenolic content was determined as
      63 mg GAE in g extract and the DPPH radical scavenging effect was determined as
      0.16 mg/mL (IC50) and TEAC was determined as 0.21mMol.

PMID- 29175773
TI  - Hyper-production of levansucrase from Zymomonas mobilis KIBGEIB14 using submerged
      fermentation technique.
AB  - The industrial utilization of enzymes requires the high yield of enzyme
      production for the synthesis of polymers by microorganisms. Therefore, it is
      necessary to optimize different production parameters of levansucrase in order to
      increase its industrial applications. Zymomonas mobilis KIBGE-IB14 was considered
      as a promising candidate for the large scale production of levan among wide range
      of microorganisms. The current investigation is aimed to optimize the production
      parameters of levansucrase by Z. mobilis KIBGE-IB14 isolated from molasses. The
      results indicated that bacterial growth as well as enzyme production was greatly
      influenced by both physical and chemical conditions. It was revealed that high
      enzyme titers were achieved at 30 degrees C with pH 6.5 after 24 hours of
      incubation in a modified medium. Moreover, the enzyme exhibited its induction in
      the presence of sucrose used as a substrate. Thus, the present study demonstrated
      that newly isolated Z. mobilis KIBGE-IB14 can be used as a plausible producer of
      levansucrase for industrial applications.

PMID- 29175774
TI  - Enhancement in spatial and recognition memory functions following long term oral
      administration of ginger extract in rats.
AB  - Ginger (Zingiber Officinale) is known over the centuries for its medicinal
      properties and has been used worldwide as health supplement and for treatment of
      several diseases. The purpose of this study was to evaluate the effects of whole
      ginger extract administration on spatial and recognition memory using
      experimental animal models. The antimicrobial properties of ginger extract
      against various pathogenic fungal and bacterial species were also examined.
      Aqueous extract of ginger at a dose of 500 mg/kg was orally administered to test
      rats and water was orally given to control rats for 6 weeks. Water Maze task (WM)
      was used to assess spatial memory and recognition memory of rats was evaluated by
      the Novel Object Recognition (NOR) task. Time spent with novel object was
      significantly increased in ginger treated rats as compared to control animals in
      novel object recognition task exhibiting enhanced recognition memory in ginger
      treated rats. Ginger treated rats exhibited significantly enhanced both short
      term memory and long term memory as evidenced by decrease in time to reach the
      hidden platform 1h and 24 h after training as compared to control rats. Short
      term memory functions of ginger treated rats were more enhanced than long term
      memory functions. Our findings suggest that ginger consumption may lead to an
      improvement in spatial and recognition memory. Significant activity of aqueous
      ginger extract was observed against pathogenic bacteria as well as fungal
      species. It is therefore suggested in this study that ginger extract can be used
      in microbial infections and as a memory enhancing drug in various memory
      disorders.

PMID- 29175775
TI  - Neuroprotective effect of Bacopa monnieri against morphine-induced
      histopathological changes in the cerebellum of rats.
AB  - Opioid addiction is associated with oxidative cell injury in neuronal cells. In
      this study, Bacopa monnieri (L.), a reputed nootropic plant, was evaluated
      against morphine-induced histopathological changes in the cerebellum of rats. B.
      monnieri methanolic extract (mBME) (40 mg/kg, p.o) and ascorbic acid (50 mg/kg,
      i.p) were administered two hours before morphine (20 mg/kg, i.p) for 14 and 21
      days. The in vitro antioxidant activity of mBME was determined by 2,2-diphenyl-1
      picrylhydrazyl (DPPH) free-radical scavenging assay. Morphine produced
      vacuolization of basket and stellate cells and reduced the size of Purkinje cells
      in the cerebellum after 14 days. However, treatment for 21 days was associated
      with severe shrinkage of Purkinje cells with loss of their characteristic flask
      shaped appearance as well as degeneration of basket, stellate and granule cells.
      Pretreatment with mBME and ascorbic acid for 14 and 21 days attenuated the
      morphine-induced histopathological changes in the cerebellum. The EC50 for the
      DPPH free-radical scavenging assay of mBME (39.06 MU/mL) as compared to ascorbic
      acid (30.25 MU/mL) and BHT (34.34 MU/mL) revealed that mBME strongly scavenged
      the free-radicals and thus possessed an efficient antioxidant propensity. These
      results concluded that B. monnieri having strong antioxidant activity exerted a
      protective effect against morphineinduced cerebellar toxicity.

PMID- 29175776
TI  - Formulation design and in vitro ex vivo evaluation of transdermal patches of
      Cinnarizine.
AB  - The aim of this study was to develop a Transdermal patch containing Cinnarizine
      using different ratios of hydrophilic and hydrophobic polymeric systems by
      solvent evaporation technique employing Polyethylene glycol (PEG 400) as
      plasticizer. The physicochemical compatibility of the drug and the polymers were
      studied by performing FT-IR spectroscopic analysis. Formulated patches were
      evaluated for physicochemical properties, skin irritation, in vitro drug release,
      ex-vivo permeation studies across rat abdominal skin and stability studies. The
      results of FT-IR studies revealed that there were no interactions between drug
      and polymers used. All the formulations exhibited uniformity in physicochemical
      properties. In vitro permeation studies of the formulations were performed by
      using Franz diffusion cells. Formulation F3 showed better permeation through rat
      skin (i.e., 8527.5+/-1.25MU/cm2 /hr) compared to rest of formulations and
      followed Fick's diffusion mechanism. On the basis of in-vitro drug release and ex
      vivo skin permeation performance, Formulation F3 containing the polymeric blend
      19:1 Hydroxypropylmethyl Cellulose (HPMC E 50cps: Eudragit RL 100) has shown
      optimum release in comparison to other formulations and indicated good physical
      stability. So it has been demonstrated that Cinnarizine can be designed as matrix
      type transdermal drug delivery system (TDDS) and further in-vivo evaluations were
      required.

PMID- 29175777
TI  - Synthesis, characterization and antinociceptive activities of Novel 2-(2,4
      dichlorophenyl)-4H-chromen-4-one.
AB  - A novel flavone derivative has been synthesized in good yield from ketone and
      aldehyde. The structure has been established by different spectroscopic
      techniques like 1H NMR, 13C NMR, IR and elemental analysis. The compound was then
      screened for its acute toxicity and antinociceptive activity studies on animal
      model. The novel compound was safe upto a maximum dose of 500mg/kg body weight
      oral dose in mice and showed 65.92 and 82.18% pheriperal analgesic activity at 15
      and 30mg/kg body weight doses. Central antinociceptive activity of the compound
      was 53.13 and 64.44% at 15 and 30mg/kg body weight respectively.

PMID- 29175778
TI  - Characterization of pathogens involved in ventilator associated pneumonia in
      surgical and medical intensive care units - A single center experience.
AB  - In the present study 60 samples were collected from lower respiratory tract of
      patients suffering from Ventilator Associated Pneumonia (VAP) admitted in
      surgical and medical Intensive Care Units (ICUs) of Khyber Teaching Hospital,
      Peshawar, Pakistan. Recovered pathogens were characterized and their
      susceptibility pattern against commonly used antibacterial agents investigated.
      Most frequent bacterial pathogen found was methicillin- resistant Staphylococcus
      aureus (MRSA) (40%) followed by members of Enterobacteriaceae (22%; of which
      Escherichia coli (50%), Klebsiella pneumonia (30%), Enterobacter cloacae (10%)
      and Citrobacter freundii (10%), Pseudomonas aeruginosa 20% and Acinetobacter
      baumannii 18%. Majority of the specimens yielded polymicrobial growth (85.75%
      polymicrobial growth compared to 14.25% specimens yielding monomicrobial growth).
      The susceptibility pattern showed that A. baumannii was the most resistant
      bacterial pathogen. Based on the results of susceptibility pattern obtained in
      the present study, combination of linezolid with meropenem and colistin has been
      found to be the best combination option for empirical therapy for VAP pathogens
      in this region.

PMID- 29175779
TI  - Growth patterns of monosodium urate monohydrate (gouty and urinary) crystals in
      gel: An in vitro study.
AB  - Monosodium urate monohydrate crystals are deposited in peripheral joints causing
      gout and elicit an intense localized inflammatory attack whereas in collecting
      ducts and medullary interstitium as a urinary calculi which causes dysuria,
      nausea and hematuria. The purpose of present study is to observe possible growth
      patterns of monosodium urate monohydrate crystals. The crystals were grown in
      test tubes by single diffusion gel technique and were observed at 7th, 14th,
      21st, 28th and 40th day. Needle and spherulite type crystals were observed at
      14th day, while arboresque, crystal sheaves, densely branched, dumbbell, mushroom
      type spherulites, plumose and hexagonal prismatic crystals were observed for the
      first time. After 40th day complete spherulites were observed with their
      aggregates. The crystals were characterized by Scanning Electron Microscopy,
      Energy-Dispersive X-ray and Fourier Transform infra Red spectroscopies. The
      pattern of MSUM will be helpful to determine the role of different natural
      products in the modulation, inhibition or promotion of these crystals by
      affecting the shape, size, transparency, approximate number and total mass of
      growing crystals. In case of inhibition or modulation it will be helpful for
      evaluation the prophylactic management whereas the promotion of the crystal will
      give an idea about the risk factors of gout and kidney stones.

PMID- 29175780
TI  - Spondias mombin L. (Anacardiaceae) enhances detoxification of hepatic and
      macromolecular oxidants in acetaminophen-intoxicated rats.
AB  - Oxidative stress is a common pathological condition associated with drug-induced
      hepatotoxicity. This study investigated Spondias mombin L. aqueous leaf extract
      on reactive oxygen species and acetaminophen-mediated oxidative onslaught in
      rats' hepatocytes. Hepatotoxic rats were orally administered with the extract and
      vitamin C for 4 weeks. The extract dose-dependently scavenged DPPH, hydrogen
      peroxide and hydroxyl radicals, with IC50 values of 0.13, 0.66, and 0.64 mg/mL,
      and corresponding % inhibitions of 89, 80, and 90%, respectively at 1.0 mg/mL.
      Ferric ion was also significantly reduced. The marked (p<0.05) increases in the
      activities of alkaline phosphatase, alanine aminotransferase and aspartate
      aminotransferase were reduced following treatment with the extract. The extract
      also significantly (p<0.05) induced the activities of antioxidant enzymes. These
      inductions reversed the acetaminophen-enhanced reduction in the specific
      activities of these enzymes as well as attenuated the observed elevated
      concentrations of autooxidized products and rived DNA in the acetaminophen
      intoxicated animals. The observed effects competed with those of vitamin C and
      are suggestive of hepatoprotective and antioxidative attributes of the extract.
      Overall, the data from the present findings suggest that S. Mombin aqueous leaf
      extract is capable of ameliorating acetaminophen-mediated oxidative hepatic
      damage via enhancement of antioxidant defense systems.

PMID- 29175781
TI  - In-silico identification and evaluation of plant flavonoids as dengue NS2B/NS3
      protease inhibitors using molecular docking and simulation approach.
AB  - Dengue infection is prevailing among the people not only from the developing
      countries but also from the developed countries due to its high morbidity rate
      around the globe. Hence, due to the unavailability of any suitable vaccine for
      rigorous dengue virus (DENV), the only mode of its treatment is prevention. The
      circumstances require an urgent development of efficient and practical treatment
      to deal with these serotypes. The severe effects and cost of synthetic vaccines
      simulated researchers to find anti-viral agents from medicinal plants. Flavonoids
      present in medicinal plants, holds anti-viral activity and can be used as vaccine
      against viruses. Therefore, present study was planned to find anti-viral
      potential of 2500 flavonoids inhibitors against the DENVNS2B/NS3 protease through
      computational screening which can hinder the viral replication within the host
      cell. By using molecular docking, it was revealed that flavonoids showed strong
      and stable bonding in the binding pocket of DENV NS2B/NS3 protease and had strong
      interactions with catalytic triad. Drug capability and anti-dengue potential of
      the flavonoids was also evaluated by using different bioinformatics tools. Some
      flavonoids effectively blocked the catalytic triad of DENV NS2B/NS3 protease and
      also passed through drug ability evaluation. It can be concluded from this study
      that these flavonoids could act as potential inhibitors to stop the replication
      of DENV and there is a need to study the action of these molecules in-vitro to
      confirm their action and other properties.

PMID- 29175782
TI  - Improved in vitro and in vivo performance of carbamazepine enabled by using a
      succinic acid cocrystal in a stable suspension formulation.
AB  - Currently cocrystals are considered as an established approach for making
      crystalline solids with overall improved physico-chemical properties. However,
      some otherwise well behaving cocrystals undergo rapid dissociation during
      dissolution, with ultimate conversion to parent drug and thus apparent loss of
      improved solubility. The polymeric carriers are long known to manipulate this
      conversion during dissolution to parent crystalline drug, which may hinder or
      accelerate the dissolution process if used in a dosage form. The goal of this
      study was to deliver in vivo a more soluble carbamazepine-succinic acid (CBZ-SUC)
      cocrystal in suspension formulation utilizing Hydroxypropyl methyl cellulose
      (HPMC-AS) as a crystallization inhibitor and Polyvinyl carpolactam-polyvinyl
      acetate-polyethylene glycol graft copolymer (r) as solubilizer. The concentration
      of these polymers were systemically varied during in vitro dissolution studies,
      while selected formulations from dissolution studies were tested in vivo.
      Pharmacokinetic studies (PK) in rabbits demonstrated that formulation F7-X (1%
      cocrystal, 1% HPMC-AS and 2% Polyvinyl carpolactam-polyvinyl acetatepolyethylene
      glycol graft co-polymer(r)) caused almost 6fold improvement in AUC0-72 (***P k
      0.05) as well as much higher Cmax of 4.73MU.mL-1 to that of 1.07MU.mL-1 of
      unformulated 'neat' cocrystal given orally. When reference formulation of CBZ (F5
      X) with similar composition to F7-X were given to rabbits, cocrystal formulation
      gave 1.37fold (***P k 0.05) bioavailability than CBZ reference formulation. Cmax
      of reference formulation observed was 3.9MUmL-1.

PMID- 29175783
TI  - Total antioxidant capacity of commonly used fruits, vegetables, herbs and spices
      of Pakistan.
AB  - The current study was aimed at investigating the total antioxidant activity (TAC)
      of various fruits, vegetables, herbs and spices habitat in Pakistan. The ferric
      reducing ability of plasma (FRAP) assay was used to measure the TAC of various
      extracts (aqueous, ethanolic and aqueous-ethanolic). Following is the potency
      order for fruits (guava >strawberry >Pomegranate >apple >kinnow >melon >lemon
      >banana), vegetables (spinach >Cabbage (Purple) >Jalapeno >Radish >Brinjal >Bell
      Pepper >Lettuce >Carrot >Cabbage (White) >Onion >Potato >Tomato >Cucumber) and
      herbs/spices (clove >Rosemary >Thyme >Oregano >Cinnamon >Cumin >Kalonji >Paprika
      >Neem (Flower) >Fennel >Black Cardamom >Turmeric >Coriander >Ginger >Garlic). In
      conclusion, the guava, spinach and clove provide the best natural dietary option
      for treatment / prevention of oxidative stress and thus could alleviate several
      associated ailments.

PMID- 29175784
TI  - Antioxidant activity of different extracts from the aerial part of Moringa
      peregrina (Forssk.) Fiori, from Jordan.
AB  - The antioxidant activities of methanol (M), ethyl acetate (E) and hexane (H)
      extracts from leaves (L) and seeds (S) of Moringa (Moringa peregrina) were
      evaluated using different model systems in vitro. Free radical scavenging
      activities were assessed by measuring the scavenging activities of leaves and
      seeds different polar extracts separately using ABTS, Hydroxyl (OH) and DPPH
      radicals. Effect of extracts on ferrous ions chelating ability and total
      antioxidant capacity were also investigated for each extract. In addition, total
      phenolics, flavonoids and flavonols content of Moringa leaves and seeds extracts
      were determined. The leaves methanol (LM) extract showed significantly the
      highest DPPH radical scavenging activity (IC50value of 5.3+/-0.2MU/ml), followed
      by leaves ethylacetate extract (LE) and seeds methanolic extract (SM) with IC50
      values of 7.1+/-0.2 and 7.2+/-0.4MU/ml, respectively. LE extract showed the
      highest ABTS radical scavenging activity with IC50value of 49.1+/-2.7MU/ml,
      followed by LM extract with IC50value of 61.2+/-1.2 MU/ml, whereas the highest
      hydroxyl radical (OH.) inhibition activity was found for LM and SM extracts with
      IC50 values of 76.9+/-0.8 and 77.5+/-1.2MU/ml, respectively. The total
      antioxidant activity was the highest in LM, LE and SM extracts (294.3, 244.5 and
      231.6MU ascorbic acid equivalent for 1mg extract, respectively). LM, LE and SM
      extracts at concentration of 100MU/ml showed the highest chelating activity
      against ferrous ions (98.4, 91.1 and 90.7%, respectively). All Moringa leaves and
      seeds extracts showed pronounced antioxidant activities in a dose dependent
      manner and the effects depend strongly on the solvent used for extraction. The
      results showed that extracts of both leaves and seeds of Moringa exhibit
      antioxidant potential suggesting that M. peregrina is a promising plant.

PMID- 29175785
TI  - Does adherence to the therapeutic regimen associate with health related quality
      of life: Findings from an observational study of type 2 diabetes mellitus
      patients in Pakistan.
AB  - Patient adherence with a therapeutic regimen predicts successful treatment and
      reduces the severity of negative complications. The purpose of this work was to
      find the relationship between general Health Related Quality of Life (HRQoL) and
      compliance to the treatment among type 2 diabetes mellitus patients (T2DM) in
      Sargodha, Pakistan. The research was planned as a cross-sectional survey. T2DM
      patients attending a tertiary care institute in Sargodha, Pakistan were targeted
      for the study. The Urdu version of the Morisky Medication Adherence Scale (MMAS
      Urdu) and EuroQol Quality of Life Scale were employed to evaluate adherence to
      treatment regimen and HRQoL correspondingly. Descriptive statistics were used for
      the elaboration of socio-demographic characteristics. The Spearman rank order
      test was employed to determine the relationship between medicine adherence and
      HRQoL. P<0.05 was considered statistically significant. A total of 392 patients
      were selected for the survey. Most participants were males (n=222, 56.6%) with
      5.58+/-4.09 years of history of T2DM. Majority of respondents (n=137, 34.9%) were
      categorized in age group of 51 to 60 years with mean age of 50.77+/-9.671 years.
      The present study highlighted that individuals with type 2 diabetes mellitus had
      decreased HRQoL (0.4715+/-0.3360) and poor medication adherence (4.44+/-1.8).
      Significant, yet weak positive correlations were observed between medication
      adherence and HRQoL (r=0.217 and 0.136 for EQ-5D and EQVAS respectively).
      Although the association between adherence to therapeutic regimen and HRQoL in
      the present study cohort was significant, it was rated as weak, hence failed in
      producing an overall impression on quality of life. The study highlights the need
      of identifying other individual factors affecting HRQoL among T2DM patients in
      Pakistan.

PMID- 29175786
TI  - Evaluation of cytotoxic and antiviral activities of aqueous leaves extracts of
      different plants against foot and mouth disease virus infection in farming
      animals.
AB  - Cytotoxic and antiviral activity of aqueous leaves extracts of three plants:
      Azadirachta indica, Moringa oleifera and Morus alba against Foot and Mouth
      disease virus (FMDV) were determined using MTT assay (3-(4, 5-Dimethylthiazol-2
      yl)-2, 5-diphenyltetrazolium bromide). Eight different concentrations of each
      plant were evaluated. Cytotoxic and antiviral activity of each extract was
      evaluated as cell survival percentage and results were expressed as Means +/-
      S.D. From the tested plant extracts, Azadirachta indica & Moringa oleifera
      exhibited cytotoxicity at 200 & 100 MU/ml respectively. In case of antiviral
      assay, Moringa oleifera showed potent antiviral activity (p<0.05) while
      Azadirachta indica showed significant antiviral activity in the range of 12.5-50
      MU/ml & 50-100 MU/ml respectively. In contrast no anti-FMDV activity in the
      present study was observed with Morus alba, although all the tested
      concentrations were found to be safe.

PMID- 29175787
TI  - Effect of medicinal plants, Heavy metals and antibiotics against pathogenic
      bacteria isolated from raw, Boiled and pasteurized milk.
AB  - Present study has been undertaken to isolate and identify the bacterial flora in
      raw, boiled and pasteurized milk. Agar disc diffusion method was used to
      determine their sensitivity using medicinal plants, antibiotics and heavy metals.
      Methylene blue reduction test was used to test the quality of milk samples. Total
      10 pathogenic strains were isolated, five strains were isolated from raw milk,
      three from boiled milk and 2 two from pasteurized milk. To determine optimum
      conditions for growth, these pathogenic microorganisms were incubated at various
      temperatures and pH. Gram's staining and biochemical tests revealed that these
      pathogenic bacteria include Lactobacillus sp., E. coli, Salmonella sp.,
      Pseudomonas sp., Streptococcus sp. and Staphylococcus. Ribotyping revealed S2 as
      Pseudomonas fluorescens, S5 as Lactococcus lactis and S9 as Lactobacillus
      acidophilus. Prevalence of pathogenic organisms provided the evidence that
      contamination of milk arises during milking, transportation and storage of milk.
      Raw milk is more contaminated than other two types of milk because it contains
      highest percentage of pathogenic organisms and pasteurized milk was found to be
      of best quality among three types. So it is recommended to drink milk after
      proper boiling or pasteurization. Proper pasteurization and hygienic packing of
      milk is essential to minimize contamination in milk which can save human beings
      from many milk borne diseases. Our study suggests that antimicrobial use in
      animal husbandry should be minimized to reduce the hazard of antibiotic
      resistance. Plant extracts are better alternative against pathogenic bacteria in
      milk.

PMID- 29175788
TI  - Abrogation of carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats
      by Ajwa date fruit extract through ameliorating oxidative stress and apoptosis.
AB  - Ajwa, a variety of date palme Phoenix dactylifera L., has long been used and
      considered as one of the most popular fruits in the North Africa and Middle East
      region. For Muslims this fruit is of religious importance and is mentioned
      several times in Quran. Besides being a part of the Arabian essential diet, dates
      have been used traditionally for number of complications. This study aimed to
      evaluate the possible potential of Ajwa date extract to guard against carbon
      tetrachloride (CCL4)-induced liver damage in rats. Adult male Sprague-Dawley rats
      were given Ajwa date extract and silymarin (a standard reference drug) at doses
      of 300 & 50mg/kg, p.o., respectively for 2 weeks before CCl4 (2 ml/kg, s. c.,
      twice weekly for 8 consecutive weeks), and concomitantly administered with CCl4
      for 8 consecutive weeks. Like silymarin, Ajwa date extract produced significant
      decrease in serum levels of alanine transaminase (ALT), aspartate transaminase
      (AST), alkaline phosphatase (ALP), total cholesterol, triglycerides (TG) and LDL
      cholesterol as well as lipid peroxides measured as malondialdehyde (MDA),
      hydroxyproline and caspase-3 contents of liver tissue with marked increase in
      serum albumin, HDL-cholesterol and reduced glutathione (GSH) content as well as
      enzyme activities of super oxide dismutase (SOD), catalase (CAT) and glutathione
      S-transferase (GST). In conclusion, Ajwa date extract afforded significant
      protection against CCl4-induced hepatocellular injury; an effect that could be
      attributed to its antioxidant, antiapoptotic and antifibrotic activities.

PMID- 29175789
TI  - Quality surveillance of immediate release aceclofenac tablets (100 mg) available
      in local market.
AB  - Aceclofenac is considered to be an effective drug that has been widely prescribed
      for multi-medical complaints globally. Owing to high demand many generic
      counterpart of aceclofenac tablets are now available in the commercial market.
      The aim of the present work is to evaluate and compare the quality attributes of
      various national/local brands of aceclofenac immediate release tablets (100mg)
      with the standard multi-national brand available in Pakistan. Physico-chemical
      evaluation was performed by determining the average tablet weight, thickness,
      hardness, disintegration time, percent dissolution and assay. Moreover, brands
      and reference formulation were exposed to multipoint dissolution. The in vitro
      drug release pattern was examined in various pH environment (1.2, 4.5 and 6.8)
      using USP dissolution apparatus 2 (paddle) at 50 rpm. The data was then analyzed
      by model dependent (Zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer &
      Peppas, and Weibull model), pair wise procedure (f1 & f2) and one-way ANOVA
      methods. Results showed that the all aceclofenac brands and the reference tablets
      followed Weibull kinetics at pH 6.8. f1 & f2 were also found to be within the
      acceptable FDA limits. Furthermore, the values of One-way ANOVA also confirmed
      the absence of any significant difference among various aceclofenac brands.

PMID- 29175790
TI  - In vitro antimicrobial, antiprotozoal activities and heavy metals toxicity of
      different parts of Ballota pseudodictamnus (L.) Benth.
AB  - The study was done to check the antimicrobial and antiprotozoal activity of
      different parts of Ballota pseudodictamnus (L.) Benth. These activities were then
      compared with the heavy metals toxicity of different parts, which plants
      accumulate in different concentrations in different parts. In in-vitro
      antileishmanial results ethanolic extract, chloroform and ethyl acetate fractions
      in roots of Ballota pseudodictamnus (L.) Benth showed antileishmanial activity.
      The ethanol, n-butanol and ethyl acetate fraction in stem revealed inhibition of
      amastigote form of leishmania. The ethanolic extract, chloroform, and n-butanol
      fraction in leaves showed inhibition of leishmanial parasite. In heavy metals
      study, Chromium was above permissible value in all parts except in leaves. Nickel
      was above WHO limit in roots. Cadmium and lead were beyond permissible limits in
      entire plant parts. Results revealed that different parts of the plant have
      different inhibition properties. So each part of plant should be checked for
      antimicrobial and antiprotozoal assay separately. It is concluded that various
      metals accumulates with miscellaneous concentrations in different plant parts.

PMID- 29175791
TI  - Cardamom extract induces cell proliferation by increasing potassium currents in
      NIH3T3 cell line.
AB  - Amommum subulatum (Roxb.) or Cardamom extract is known to have anti-inflammatory
      and neuroprotective effects towards many gastrointestinal related problems.
      However, uptill now different fractions of cardamom extract on fibroblasts with
      respect to potassium channel activity have not been investigated. Therefore,
      present study investigated the effects of different fractions of cardamom extract
      on potassium channels in non-tumor NIH3T3 cell line. Phytochemical analysis of
      hydroalcoholic, n-hexane, butane and ethyl acetate fractions of cardamom extracts
      were purified and isolated by thin layer chromatography (TLC). 3T3 cells were
      cultured and incubated with hydroalcohol (1-2 MU/ml), n-hexane (1 MU/ml), butane
      (2 MU/ml) and ethyl acetate (1-2 MU/ml) for 5 hrs at 37 degrees C. Modulation in
      potassium currents were recorded by whole-cell patch clamp method. The data
      showed two constituents Cineol (C10H18O) and Terpinyl acetate (C10H17OOCCH3) by
      TLC method. The present study shows that the constituents in n-hexane, hydro
      alcohol (1 MU/ml) and ethyl acetate (2 MU/ml) significantly increased (p<0.01)
      the potassium outward rectifying currents from NIH3T3 cells when compared to
      untreated controls cells. Whereas, butanol fraction (2 MU/ml) significantly
      decreased (p<0.01) the inward rectifying currents when compared to controls.
      Moreover hydroalcoholic and n-hexane fractions have increased the proliferation
      in 3T3 cell line. On the other hand butanol and ethyl acetate did not induce
      proliferation in 3T3 cells. Taken together, our data suggested that cardamom
      extract contains constituents that increased K+ currents, cell migration and
      proliferation and are involved in wound healing.

PMID- 29175792
TI  - Preliminary phytochemical screening, antioxidant and antihyperglycaemic activity
      of Moringa oleifera leaf extracts.
AB  - Moringa oleifera plant has been widely used for a vast number of folkloric
      medicinal purposes. The research aimed to investigate the antioxidant and
      antihyperglycaemic activity of Moringa oleifera leaf extracts obtained using
      different solvent systems for extraction. The solvent extracts of Moringa
      oleifera were: water extract (100% MoWE), 50% Methanolic extract (50% MoME), 100%
      Methanolic extract (100% MoME), 50% Ethanolic extract (50% MoEE), and 100%
      Ethanolic extract (100% MoEE). The in vitro antioxidant activity was evaluated by
      the use of the 1,1-diphenyl-2-picryl hydrazyl (DPPH) scavenging assay which
      showed the hydro-alcoholic extracts to have the highest reducing power, though
      lower than that of the standard, vitamin C. The hypoglyceamic activity was
      evaluated for the extracts at graded doses of 200mg/kg, 300mg/kg and 400mg/kg in
      wistar rats. Relative to the positive control, all treatment groups showed a
      significant statistical decrease in blood glucose levels. The decrease trends as
      metformin (84.14%) >50% MoEE 300mg/kg (83.72%) >MoWE 300mg/kg (82.42%) > 50% MoEE
      200mg/kg (82.32%) >100% MoEE 400mg/kg (81.96%) >50% MoME (80.69%) >100% MoME
      300mg/kg (78.47%) >50% MoME 200mg/kg (66.34%). Overall, the 50% MoEE at a dose of
      300mg/kg showed superior antioxidant properties, weight restorative and
      pronounced hypoglyceamic effects. The weight restorative effect of high dose
      alcoholic extract of Moringa oleifera was also observed in the study. This study
      establishes novel and foundational considerations for further isolation and
      characterization studies for the hypoglyceamic compounds in the plant.

PMID- 29175793
TI  - Role of ALAD and VDR genotypes on the association of low blood lead level with
      serum uric acid and blood pressure in automobile paint workers of Karachi,
      Pakistan.
AB  - Lead is an environmental pollutant having nephrotoxic effects even at low level.
      Its continuous exposure is associated with increased serum uric acid level that
      resulting in renal insufficiency. This research was conducted to see the effects
      of delta-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR)
      genotypes on biochemical parameters and blood pressure (BP) of automobile workers
      having low blood lead level (BLL) with continuous lead exposure. Automobile
      paints workers with ALAD 1-2 genotype showed the positive association of BLL with
      diastolic BP (p<0.05) whereas, a genotypic combination of ALAD 1-2/VDR BB showed
      the negative association of serum uric acid with BLL (p<0.05). Similarly negative
      effects of VDR BB genotype (p<0.01) and ALAD 1-2 genotype (p<0.05) were observed
      in the association of serum uric acid with BLL at the mean age >=30 years. This
      suggests that automobile paint workers having ALAD 1-2 genotypes are at the risk
      of increased diastolic BP. The research also foretells that combination of ALAD 1
      2/VDR BB may play a significant role against lead induced nephrotoxicity at low
      BLL with continuous lead exposure.

PMID- 29175794
TI  - Cost effectiveness evaluation of hepatitis C therapy in Lahore.
AB  - Approximately 10 million Pakistan's of population is a victim of Hepatitis C
      virus. A comparative study of two treatments for Hepatitis C being provided in
      private clinics and government hospitals was conducted to evaluate the cost
      effectiveness of these treatments. The quality adjusted life years (QALYs) for
      each treatment plan was determined with the help of health utilities, using EQ-5D
      scores. A comprehensive data collection form aided in scrutinizing the cause and
      effect of each treatment on the patient's quality of life. The total sample size
      for this study is 200 total from the public and private sectors. For both the
      treatment strategies, values for quality adjusted life years (QALYs), incremental
      cost effective ratio (ICER) and cost effective analysis (CEA) were calculated.
      The Hepatitis C virus 3a and 3b genotypic patients who were treated with
      pegylated interferon alpha-2a and ribavirin combination (strategy 2) showed an
      increased quality adjusted life years (QALYs) of two years, as compared to those
      who received interferon alpha-2a and ribavirin regimen (strategy 1). An
      incremental cost effectiveness ratio (ICER) of Rs 144673.5 per quality adjusted
      life year (QALYs) was gained by patients treated with strategy 2. The therapy
      followed by the government sector (strategy 1) is relatively inexpensive
      accounting for Rs 654.5/quality adjusted life years (QALY) and therapy provided
      at the clinic sector (strategy 2) is relatively expensive Rs 5620.6/ quality
      adjusted life years (QALY). However, the cost effectiveness analysis for the
      pegylated interferon therapy is quite comparable with the other standard
      treatments; hence it can be called cost effective according to the quality
      adjusted life years (QALYs) gained and efficacy of the said therapy.

PMID- 29175795
TI  - Phytochemical screening, GC-MS analysis and in vitro antioxidant activity of
      pollen of Centella asiatica (Linn) urban a traditional medicinal plant.
AB  - In the present study the crude extracts of pollen of Centella asiatica (Linn.)
      Urban were explored for their antioxidant potential using Ferric Reducing Power,
      Metal Chelating Activity and Trolox Equivalent Antioxidant Capacity assays. In
      crude extracts of pollen antioxidant components were initially extracted in
      methanol and further fractionated in solvents of different polarity, such as n
      Hexane, Chloroform, Ethyl Acetate and Water exhibited reasonable antioxidant
      activity. The extract was found to contain large amounts of phenolic and
      flavonoid contents ranged from 143-1155 mg/l of gallic acid equivalent (GAE) and
      911-2488 mg/l of quercetin (QE) respectively. Moreover, Super oxide Anion Radical
      Scavenging Activity and GS-MS analysis were also carried out.

PMID- 29175796
TI  - Antimicrobial susceptibility of organisms isolated from sputum culture of
      Karachi, Pakistan.
AB  - Our study aims to contribute to developing antibiotics prescription guidelines at
      a national and a regional level directed by the antibiotics susceptibility
      patterns and rapidly emerging resistant organisms. This study is designed to
      observe the antimicrobial susceptibility in sputum culture isolates and drug
      resistance patterns against various antimicrobials. This was a retrospective
      cohort study; data was collected from two laboratories from 1st Jan to 15 July
      2007. All laboratory reports were analyzed using SPSS version 19.0.The sputum
      culture was found positive for microbial growth in 217 reports out of 864 total
      (25.11%). The leading organisms were 25.8% Klebsiella pneumoniae, 23.5%
      Streptococcus pneumoniae, 18% Pseudomonas aeruginosa and 12.9% Staphylococcus
      aureus. S.pneumoniae and S.aureus were sensitive to the combination of beta
      lactam antibiotics and anti-beta lactamase while K.pneumoniae and P. aureginosa
      were susceptible to fluoroquinolones, macrolides and aminoglycosides. The total
      yield of sputum culture was 25.11%. The gram positive cocci which were isolated
      were mostly resistant to beta lactam antibiotics alone i.e. only 45% of S.
      pneumoniae and 33% of S. aureus were sensitive to Amoxicillin alone. Sensitivity
      to Co-amoxiclav was still high. 90% and 85% of S. pneumonia and S. aureus
      respectively were sensitive to Co-amoxiclav. The P. aeruginosa resistance to
      Amikacin in our study is 10%.

PMID- 29175797
TI  - Diagnosis of hepatitis C in pregnant mothers and its transfer pattern in
      neonates.
AB  - Hepatitis is the most common liver diseases in the Pakistan caused by blood-borne
      infection of HCV. Viral transmission is frequent through blood contact. Vertical
      transmission is transfer of disease from mother to infant. The women who are
      infected with hepatitis C virus RNA are at high risk of infecting their babies.
      Actual transmission occurs during labor and at time of delivery when blood of
      both mother and neonate is in contact with each other. Vertical transmission rate
      is lowered when mother is HCV RN A negative. The project was designed to
      determine the percentage of transmission and prevalence of Hepatitis C virus from
      mother to neonates. Assessment of the quantitative analysis of RNA levels in
      mother blood and viraemic status from the early postpartum period onwards of
      children born to HCV infected mothers. For the diagnosis of hepatitis C in
      mothers, blood samples of fifty HCV pregnant women between 23-41 years old were
      taken. The blood samples were centrifuged at 8,000 rpm and serum was separated
      and stored at 40C. The values of the Alanine Aminotransferase was determined at
      2nd and 3rd trimester of pregnancy. After extraction HCVRN Awere transcribed and
      amplified by PCR. The samples were further authenticated through the Agarose Gel
      Electrophoresis system and bands were obtained. Nested reverse transcription PCR
      (RT-PCR) was conducted for the quantitative analysis of HCV-RNA. The results
      showed that in 66% cases, the mothers had high level of ALT at 2nd trimester of
      pregnancy. Their ALT level was decreased in the 3rd trimester of pregnancy. PCR
      results showed that 40% pregnant women had quantity of HCV-RNA in the range of
      1000-10,000 IU/mL and in 18% women were above 100000 The results of
      spectrophotometer showed that 80% infants had the antibodies against HCV-RNA
      while only 20% of the neonates did not have antibody right after birth. The 29%
      babies got HCV-RNA in their serum and became positive for HCV-RNA.

PMID- 29175798
TI  - Report: Potential of nano-emulsions as phytochemical delivery system for food
      preservation.
AB  - Nature is a rich source of bioactive phytochemicals. These plant based compounds
      have rich scope as antioxidants, antimicrobial compounds and food preservatives
      and so for long time to be used in meat, fruits, vegetables and processed food
      items, either as added preservative or as coating material in various food
      applications, but the major limitation is their limited solubility in a food
      grade medium. Nano-emulsion is a best choice as a medium having vast area of
      application. The major advantage of nano-emulsion would be the solubility of a
      vast group of compounds, due to the presence of water and lipid phases. In this
      way, nano-emulsions can be proved to be the most suitable candidate as
      phytochemical delivery system for food preservation. In present article, the use
      of phytochemicals as potent food preservatives has been reviewed, in context of
      solubility of phytochemicals in nano-emulsion and applications of food grade nano
      emulsions to food systems.

PMID- 29175799
TI  - Report: Prevalence and antibiotic trials against Salmonella enterica isolated
      from diarrheic lambs and kids.
AB  - Salmonella enterica (S. enterica) is the major zoonotic threat for small
      ruminants and humans responsible for huge economic losses and high mortality in
      Pakistan. Lambs and kids of Lahore district were examined to determine the
      prevalence, hematology and chemotherapy of S. enterica. A total of 200 diarrheic
      samples (n=100 lambs; n=100 kids) were collected and examined; 59 (29.50%) were
      found positive for S. enterica. Lambs had lightly greater prevalence (31%) than
      kids (29%). The frequency analysis (OR=1.16 [reciprocal =0.87]) showed non
      significant difference in both the lambs and kids. The significant decrease
      (PR0.001) in hemoglobin, pack cell volume and total erythrocyte count was
      observed in infected lambs and kids. Results of in-vitro antibiotic
      susceptibility test revealed that S. enteric isolated from both lambs and kids
      were susceptible to levofloxacin, ciprofloxacin, ofloxacin, gentamicin,
      azithromycin, tobramycin, amoxicillin, ampicillin and nalidixic acid. Where as
      the results of in vivo antibiotic trials showed that isolates from both lambs and
      the kids with diarrhea were susceptible to levofloxacin and ciprofloxacin.

PMID- 29175800
TI  - Report: Computational drug designing of newly synthesized triazoles against
      potential targets of methicillin resistant Staphylococcus aureus.
AB  - Methicillin resistant Staphylococcus aureus (MRSA) is resistant to known
      antibiotics and has become a great challenge for healthcare professionals,
      therefore new molecules are needed to manage this situation. In this study, new
      lead molecules 4-Amino-5-(2-Hydroxyphenyl)-1,2,4-Triazol-3-Thione (U1) and4-(2
      hydroxybenzalidine) amine-5-(2-hydroxy) phenyl-1,2,4-triazole-3-thiol(U1A Schiff
      base) were synthesized by fusion method that showed promising antibacterial
      activity (U1A: 26mm and U1: 14mm) against MRSA.FT-IR and NMR were used for
      structural characterization of these derivatives and their toxicity properties
      were assessed by Lipinski's rule of 5. New potential drug targets of this
      bacterium were also identified by comparative and subtraction genomics
      techniques. In particular, octanoyl-[GcvH]: protein N-octanoyl transferase and
      phosphor mevalonate kinase were used as potential targets in AutoDock Vina
      studies. This study can provide a framework to find potential drug targets for
      other pathogenic microorganisms that can successfully be docked with compound U1
      and U1A.

PMID- 29175801
TI  - Report: Cytotoxic activities of Rosa brunonii, Calligonum polygonoides, Pegnum
      harmala and Sueda fruticosa extract using brine shrimp.
AB  - The present study was carried out to record and evaluate the effect of Rosa
      brunonii, Calligonum polygonoides, Sueda fruticosa and Pegnum harmala L.,
      extracts on brine shrimp collected during March-June 2013 from different regions
      of District Bannu. These four plants were medicinal xerophytes and widely
      distributed throughout Pakistan. Rosa brunonii is commonly used as a hedge plant
      for gardening. Calligonum polygonoides and Sueda fruticosa are locally used as a
      fuel, while Pegnum harmala (L.) is the most important multipurpose medicinal
      xeric plant, which is used for various purposes. All these selected medicinal
      xerophytes have inhibitory effect on bacterial growth. In this study the effect
      of different concentration (10-70 MU/ml) were tested on brine shrimp. The results
      showed that maximum cytotoxic activities were observed in Rosa brunonii (100.0+/
      0.4), Calligonum polygonoides (100.0+/-0.2) and Pegnum harmala (L.) (90.0+/-5.2)
      while Sueda fruticosa (50.0+/-7.1) has less cytotoxic property. These activities
      are may be due to the presence of bioactive constituents.

PMID- 29175803
TI  - Review: Nanopreparations for better drug delivery.
AB  - Nanomedicines are a recent development to face medical and pharmaceutical
      challenges because nanoparticles have unique properties. They are very small in
      size and are easy to handle. One more advantage is that they are not harmful for
      the human body. Poorly soluble drugs have serious problems with their delivery
      and dosage forms. Formulation strategies by means of nanocarrier systems, such as
      polymeric micelles, can resolve the trouble. Micelles from PEG-diacyllipids, e.g.
      PEG-PE, are of special attention. On the other hand, the layer-by-layer (LbL)
      technique can be useful to set up stable nanocolloids of low solubility. In some
      cases, the use of nanopreparations is the only way to fulfill medical
      requirements. Thus, for the blood group CT imaging, one has to prepare long
      circulating contrast-loaded nanoparticles. In other cases, poor stability of
      potential drugs creates a problem, such as with siRNA, and the use of
      nanocarriers may present a solution e.g. Polymeric micelles having a hydrophobic
      derivative of siRNA. We will discuss the preparation, properties, and anti-cancer
      activity of drug-loaded PEG-PE micelles and LbL nanoparticles and other
      "approaches" for making "undeliverable" substances deliverable. Injectable,
      implantable, topical delivery of active compounds, oral drug delivery system and
      many other methods have been improved by nanotechnology.

PMID- 29175802
TI  - Review: Ethnomedicinal, phytochemical and antibacterial activities of medicinal
      flora of Pakistan used against Pseudomonas aeruginosa-A Review.
AB  - Medicinal plants have been used from ancient time against different infectious
      diseases caused by microorganisms across the globe. The present review represents
      different medicinal plants of Pakistan used traditionally for the treatment of
      variety of ailments caused by Pseudomonas aeruginosa, their in-vitro activities
      against P. aeruginosa and phytochemistry. These plants were extracted with
      different solvents that showed good in-vitro activities against P. aeruginosa,
      due to the presence of active phytoconstituents including alkaloids, terpenoids
      etc. Among all the solvents used for extraction process, alcoholic extracts were
      mostly preferred in Pakistan. However, non-alcoholic solvents like ethyl acetate
      and chloroform also showed good anti-P. aeruginosa activities. Statistically,
      increase in concentration (mg/ml) of ethyl acetate and chloroform extracts
      significantly increase (p=0.000 and p= 0.046) inhibitory activity against P.
      aeruginosa. This review provides scientific validation of the traditional
      knowledge in using medicinal plants for the treatment of different diseases
      caused by this bacterium. Reported Pakistani medicinal plants contain variety of
      phytochemical compounds that could be very useful in the production of new drugs
      with fewer side effects on living system compared to some allopathic drugs. This
      review also provides baseline information for future research studies on the
      phytochemistry of unexplored plants. Further research studies should be carried
      out on non-alcoholic extracts that could be helpful in the extraction new
      compounds, which could lead to the development of some novel drugs in the
      pharmaceutical industries of Pakistan.

PMID- 29175804
TI  - Review: Medicinal plants combating against hypertension: A green antihypertensive
      approach.
AB  - Hypertension (HTN) or high blood pressure is a medical condition that accounts
      9.4 million deaths all over the world every year. It is leading cause of
      morbidity and mortality worldwide. It increases the risk of cardiovascular
      diseases, including heart failure, diffuse atherosclerosis, cognitive impairment
      and dementia. Clinically, synthetic antihypertensive drugs have been used to
      treat hypertension. However, the efficacy of these drugs is low and also produces
      side effects which include dry mouth, dizziness, emotional distress,
      gastrointestinal disturbance, visual disorders etc. These distressing side
      effects adversely affect health-related quality of life. Therefore, there is a
      need to search natural, cheaper and non-toxic compound. Plant are widely use in
      traditional systems of medicine for the treatment of several diseases. About 80%
      of the world population relies on traditional medicine for primary healthcare. In
      the last three decades, a lot of research has been done on local medicinal plants
      for hypotensive and antihypertensive potentials. Plants are the rich source of
      secondary metabolites which have been found in vivo to have antihypertensive
      properties. The current study is focused on reviewing the antihypertensive
      property of medicinal plants and their metabolites. In the current review, we
      conducted a literature search using Elsevier, Science direct, Springer Link
      (Springer), Pub Med and Google Scholar. The search included the keywords
      "plants", "medicinal plants", "plant extracts", cross-referenced with the
      keywords "hypertension" "antihypertensive activity". The use of plant origin
      natural compounds as cardio protective and antihypertensive agents is an
      interesting strategy for discovering bioactive products. Plants are rich in a
      variety of secondary metabolites, such as flavonoids, alkaloids, tannins and
      terpenoids. These have been found in vivo to have antihypertensive effects. The
      present review therefore; stand for a good basis to choose exact molecules
      belonging to the indicated categories that in the forthcoming future will become
      useful therapeutic tools.

PMID- 29175805
TI  - Review: Autologous blood transfusion drainage compared with no drainage in total
      knee arthroplasty: A meta-analysis and systematic review.
AB  - This is the first meta-analysis to assess the clinical efficiency, safety and
      potential advantages regarding the use of ABT drains compared with no drainage
      which is controversial in total knee arthroplasty (TKA).A comprehensive
      literature search was carried out in March 2015 using the PubMed, Embase, and
      Cochrane Library databases. A metaanalysis was carried out on two retrospective
      comparative studies (RCSs) and five randomized controlled trials (RCTs). The
      number of patients receiving homologous blood transfusion was the primary outcome
      of the meta-analysis; the secondary outcome measure was the mean drop in Hb level
      in comparison to the mean pre-operative HB level, the range of flexion of the
      knee joint, and infections of the wound after surgery. A total of 868 patients,
      who were included in two retrospective studies and five RCTs, were distributed
      into subgroups for the meta-analysis. This pooled data showed no benefit of ABT
      drainage compared no drainage in the homologous blood transfusion rate (13.05%
      and 16.91%, OR:0.73[0.47,1.13], Z=1.41, P=0.016; and 3.49% and 6.54%, OR:
      0.50[0.12,2.01], Z=0.98,P=0.033,respectively in subgroups), Hb drop (Weight mean
      differences (WMD): 0.20[-0.28,0.68], Z=0.82, P=0.41; WMD:0.16[-0.41,0.55],
      Z=0.93, P=0.35, respectively), range of flexion of the knee joint (WMD:-0.82 [
      3.35,1.70], Z =0.64,P=0.52)and wound infection (OR:0.25[0.61,10.20]; Z =1.28,
      p=0.2) after TKA surgery. Our findings do not recommend the routine use of
      postoperative ABT drainage in total knee arthroplasty. Well-designed RCTs with
      large sample sizes, longer term measures and extensive follow-up period should be
      performed in the future to update the findings of this study.

PMID- 29175806
TI  - The Distribution of Different Types of Diabetes in Childhood: A Single Center
      Experience
AB  - OBJECTIVE: Type 1 diabetes (T1D) is the most common cause of diabetes in
      childhood but type 2 diabetes (T2D) and maturity onset diabetes of the young
      (MODY) are emerging as noteworthy causes of diabetes at young ages. The aim is to
      determine the distribution, trends and clinical features of the different types
      of diabetes in childhood in one tertiary center. METHODS: The records of children
      and adolescents aged 0-18 years who were diagnosed as "diabetes/persistent
      hyperglycemia" between January 1999 and December 2016, were reviewed. Clinical
      and laboratory characteristics of the patients at diagnosis and type of diabetes
      were recorded. RESULTS: The mean +/- standard deviation age of 835 patients
      (48.7% females) at diagnosis was 8.8+/-4.4 years. Eighty-four percent of the
      patients were diagnosed as T1D, 5.7% as T2D, 5.3% as clinical MODY and 5% as
      being cases of other types of diabetes. The frequency of diabetic ketoacidosis
      (DKA) and severe DKA in T1D were 48.4% and 11.6%, respectively. Fourteen patients
      (29.2%) with T2D presented with ketosis and two of them (4.2%) had DKA at
      diagnosis. Antibody positivity was 83.1% in T1D and 14.8% in T2D. A statistically
      significant increase in the frequency of T2D has clearly been demonstrated in
      recent years with a frequency of 1.9%, 2.4% and 7.9% in 1999-2004, 2005-2010 and
      2011-2016, respectively (p<0.001). In MODY, genetic analysis was performed in 26
      (59%) patients and HNF1A and GCK gene mutations were detected in 3 (11.5%) and 14
      (53.8%) patients, respectively. CONCLUSION: Although the most frequent cause of
      DM is T1D in childhood, a trend towards increase in the frequency of T2D in
      recent years is notable in our population.

PMID- 29175807
TI  - Restless Legs Syndrome and Poor Sleep Quality in Obese Children and Adolescents
AB  - OBJECTIVE: Adult epidemiological studies suggest that the rate of Restless Legs
      syndrome (RLS) in the general population may range from 5% to 15%. The aim of
      this study was to investigate the frequency of RLS in a community sample of obese
      adolescents aged 10-16 years and to assess the association with sleep quality and
      health-related glucose metabolism markers. METHODS: The study group comprised 144
      obese and overweight children aged 10-16 yearsand the control group consisted of
      66 age-matched healthy children. The RLS Questionnaire devised by the
      International RLS Study and the Pittsburgh Sleep Quality Index (PSQI), where a
      score >5 indicates poor sleep quality, was used to assess sleep quality. RESULTS:
      Mean body mass index (BMI) of  the overweight/obese and control groups were
      30.5+/-0.5 and 18.7+/-0.2, respectively. The frequency of RLS was higher in the
      obese group (21.7%) than the overweight (3.4%) and control (1.5%) (p<0.001)
      groups. The frequency of a poor PSQI score was significantly higher (p<0.001) in
      the obese group (37.3%) than the control group (24.2%). The obese with RLS group
      also had poorer sleep quality scores than the non-RLS obese group. Many symptoms
      of sleep disruption were more common in obese patients with RLS and RLS was
      independently correlated with a high PSQI score [odds ratio (OR): 2.25,
      confidence interval (Cl): 0.96-5.28, p<0.001)] and an increased BMI z-score (OR:
      8.87, Cl: 2.04-38.61, p<0.001). CONCLUSION: RLS is common in obese children and
      may be associated with altered sleep quality. Obese children with RLS need to be
      assessed since they may need support to improve their sleep quality.

PMID- 29175808
TI  - Time Gain Needed for In-Ambulance Telemedicine: Cost-Utility Model.
AB  - BACKGROUND: Stroke is a very time-sensitive pathology, and many new solutions
      target the optimization of prehospital stroke care to improve the stroke
      management process. In-ambulance telemedicine, defined by live bidirectional
      audio-video between a patient and a neurologist in a moving ambulance and the
      automated transfer of vital parameters, is a promising new approach to speed up
      and improve the quality of acute stroke care. Currently, no evidence exists on
      the cost effectiveness of in-ambulance telemedicine. OBJECTIVE: We aim to develop
      a first cost effectiveness model for in-ambulance telemedicine and use this model
      to estimate the time savings needed before in-ambulance telemedicine becomes cost
      effective. METHODS: Current standard stroke care is compared with current
      standard stroke care supplemented with in-ambulance telemedicine using a cost
      utility model measuring costs and quality-adjusted life-years (QALYs) from a
      health care perspective. We combine a decision tree with a Markov model. Data
      from the UZ Brussel Stroke Registry (2282 stroke patients) and linked hospital
      claims data at individual level are combined with literature data to populate the
      model. A 2-way sensitivity analysis varying both implementation costs and time
      gain is performed to map the different cost-effective combinations and identify
      the time gain needed for cost effectiveness and dominance. For several modeled
      time gains, the cost-effectiveness acceptability curve is calculated and mapped
      in 1 figure. RESULTS: Under the base-case scenario (implementation cost of US
      $159,425) and taking a lifetime horizon into account, in-ambulance telemedicine
      is a cost-effective strategy compared to standard stroke care alone starting from
      a time gain of 6 minutes. After 12 minutes, in-ambulance telemedicine becomes
      dominant, and this results in a mean decrease of costs by US -$30 (95% CI -$32 to
      -$29) per patient with 0.00456 (95% CI 0.00448 to 0.00463) QALYs on average
      gained per patient. In over 82% of all probabilistic simulations, in-ambulance
      telemedicine remains under the cost-effectiveness threshold of US $47,747.
      CONCLUSIONS: Our model suggests that in-ambulance telemedicine can be cost
      effective starting from a time gain of 6 minutes and becomes a dominant strategy
      after approximately 15 minutes. This indicates that in-ambulance telemedicine has
      the potential to become a cost-effective intervention assuming time gains in
      clinical implementations are realized in the future.

PMID- 29175809
TI  - Two Novel Cognitive Behavioral Therapy-Based Mobile Apps for Agoraphobia:
      Randomized Controlled Trial.
AB  - BACKGROUND: Despite the large body of literature demonstrating the effectiveness
      of cognitive behavioral treatments for agoraphobia, many patients remain
      untreated because of various barriers to treatment. Web-based and mobile-based
      interventions targeting agoraphobia may provide a solution to this problem, but
      there is a lack of research investigating the efficacy of such interventions.
      OBJECTIVE: The objective of our study was to evaluate for the first time the
      effectiveness of a self-guided mobile-based intervention primarily targeting
      agoraphobic symptoms, with respect to a generic mobile app targeting anxiety.
      METHODS: A Web-based randomized controlled trial (RCT) compared a novel mobile
      app designed to target agoraphobia (called Agoraphobia Free) with a mobile app
      designed to help with symptoms of anxiety in general (called Stress Free). Both
      interventions were based on established cognitive behavioral principles. We
      recruited participants (N=170) who self-identified as having agoraphobia and
      assessed them online at baseline, midpoint, and end point (posttreatment) over a
      period of 12 weeks. The primary outcome was symptom severity measured by the
      Panic and Agoraphobia Scale. RESULTS: Both groups had statistically significant
      improvements in symptom severity over time (difference -5.97, 95% CI -8.49 to 
      3.44, P<.001 for Agoraphobia Free and -6.35, 95% CI -8.82 to -3.87, P<.001 for
      Stress Free), but there were no significant between-group differences on the
      primary outcome (difference 0.38, 95% CI -1.96 to 3.20, P=.64). CONCLUSIONS: This
      is, to our knowledge, the first RCT to provide evidence that people who identify
      as having agoraphobia may equally benefit from a diagnosis-specific and a
      transdiagnostic mobile-based intervention. We also discuss clinical and research
      implications for the development and dissemination of mobile mental health apps.
      TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number
      (ISRCTN): 98453199; http://www.isrctn.com /ISRCTN98453199 (Archived by WebCite at
      http://www.webcitation.org/6uR5vsdZw).

PMID- 29175810
TI  - Reduction in Vegetable Intake Disparities With a Web-Based Nutrition Education
      Intervention Among Lower-Income Adults in Japan: Randomized Controlled Trial.
AB  - BACKGROUND: No existing Web-based nutrition education interventions have been
      evaluated in light of socioeconomic status just in Japan. OBJECTIVE: The aim was
      to investigate the effect of a Web-based intervention program on reducing
      vegetable intake disparities between low- and middle-income Japanese adults.
      METHODS: In this randomized controlled trial, participants were assessed at three
      time points-baseline, postintervention (5 weeks later), and a follow-up after 3
      months-from October 2015 to March 2016. We collected data via a Japanese online
      research service company from 8564 adults aged 30 to 59 years. Participants were
      stratified according to national population statistics for gender and age, and
      randomly selected. They were then randomly allocated into intervention (n=900)
      and control (n=600) groups such that both groups contained an equal number of
      individuals with low and middle income. The intervention program encouraged
      behavior change using behavioral theories and techniques tailored to their
      assumed stage of change. The outcome was vegetable intake servings per day (1
      serving being approximately 70 g). RESULTS: Out of 900 participants who started,
      450 were from the middle income group (of which 386 or 85.7% completed the
      intervention), and 450 were from the low income group (of which 371 or 82.4%
      completed). In the intervention group, vegetable intake increased in the low
      income participants from baseline to postintervention (0.42 servings, 95% CI 0.11
      0.72). A two-way analysis of variance showed that low-income participants had
      significant main effects of group (eta2=0.04, P=.01) and time (eta2=0.01,
      P<.001), and a significant interaction (eta2=0.01, P=.009). Middle-income
      participants also had a significant main effect of time (eta2=0.01, P=.006) and a
      significant interaction (eta2=0.01, P=.046). CONCLUSIONS: This Web-based
      nutritional education intervention could fill the vegetable intake gap between
      low- and middle-income adults in Japan, and is expected to prevent
      noncommunicable and lifestyle-related diseases. Further intervention program
      improvements are necessary to maintain and increase vegetable intake for other
      groups. TRIAL REGISTRATION: Current Controlled Trials (UMIN-ICDR): UMIN000019376;
      https://upload.umin.ac.jp/cgi-open-bin/ icdr_e/ctr_view.cgi?recptno=R000022404
      (Archived by WebCite at http://www.webcitation.org/6u9wihBZU).

PMID- 29175811
TI  - Social Media Interventions to Promote HIV Testing, Linkage, Adherence, and
      Retention: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Social media is increasingly used to deliver HIV interventions for
      key populations worldwide. However, little is known about the specific uses and
      effects of social media on human immunodeficiency virus (HIV) interventions.
      OBJECTIVE: This systematic review examines the effectiveness of social media
      interventions to promote HIV testing, linkage, adherence, and retention among key
      populations. METHODS: We used the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) checklist and Cochrane guidelines for this
      review and registered it on the International Prospective Register of Systematic
      Reviews, PROSPERO. We systematically searched six databases and three conference
      websites using search terms related to HIV, social media, and key populations. We
      included studies where (1) the intervention was created or implemented on social
      media platforms, (2) study population included men who have sex with men (MSM),
      transgender individuals, people who inject drugs (PWID), and/or sex workers, and
      (3) outcomes included promoting HIV testing, linkage, adherence, and/or
      retention. Meta-analyses were conducted by Review Manager, version 5.3. Pooled
      relative risk (RR) and 95% confidence intervals were calculated by random-effects
      models. RESULTS: Among 981 manuscripts identified, 26 studies met the inclusion
      criteria. We found 18 studies from high-income countries, 8 in middle-income
      countries, and 0 in low-income countries. Eight were randomized controlled
      trials, and 18 were observational studies. All studies (n=26) included MSM; five
      studies also included transgender individuals. The focus of 21 studies was HIV
      testing, four on HIV testing and linkage to care, and one on antiretroviral
      therapy adherence. Social media interventions were used to do the following:
      build online interactive communities to encourage HIV testing/adherence (10
      studies), provide HIV testing services (9 studies), disseminate HIV information
      (9 studies), and develop intervention materials (1 study). Of the studies
      providing HIV self-testing, 16% of participants requested HIV testing kits from
      social media platforms. Existing social media platforms such as Facebook (n=15)
      and the gay dating app Grindr (n=10) were used most frequently. Data from four
      studies show that HIV testing uptake increased after social media interventions
      (n=1283, RR 1.50, 95% CI 1.28-1.76). In the studies where social media
      interventions were participatory, HIV testing uptake was higher in the
      intervention arm than the comparison arm (n=1023, RR 1.64, 95% CI 1.19-2.26).
      CONCLUSIONS: Social media interventions are effective in promoting HIV testing
      among MSM in many settings. Social media interventions to improve HIV services
      beyond HIV testing in low- and middle-income countries and among other key
      populations need to be considered. TRIAL REGISTRATION: International Prospective
      Register of Systematic Reviews (PROSPERO): CRD42016048073;
      http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42016048073 (Archived
      by WebCite at http://www. webcitation.org/6usLCJK3v).

PMID- 29175812
TI  - The Role of Transfer in Designing Games and Simulations for Health: Systematic
      Review.
AB  - BACKGROUND: The usefulness and importance of serious games and simulations in
      learning and behavior change for health and health-related issues are widely
      recognized. Studies have addressed games and simulations as interventions, mostly
      in comparison with their analog counterparts. Numerous complex design choices
      have to be made with serious games and simulations for health, including choices
      that directly contribute to the effects of the intervention. One of these
      decisions is the way an intervention is expected to lead to desirable transfer
      effects. Most designs adopt a first-class transfer rationale, whereas the second
      class of transfer types seems a rarity in serious games and simulations for
      health. OBJECTIVE: This study sought to review the literature specifically on the
      second class of transfer types in the design of serious games and simulations.
      Focusing on game-like interventions for health and health care, this study aimed
      to (1) determine whether the second class of transfer is recognized as a road for
      transfer in game-like interventions, (2) review the application of the second
      class of transfer type in designing game-like interventions, and (3) assess
      studies that include second-class transfer types reporting transfer outcomes.
      METHODS: A total of 6 Web-based databases were systematically searched by titles,
      abstracts, and keywords using the search strategy (video games OR game OR games
      OR gaming OR computer simulation*) AND (software design OR design) AND (fidelity
      OR fidelities OR transfer* OR behaviour OR behavior). The databases searched were
      identified as relevant to health, education, and social science. RESULTS: A total
      of 15 relevant studies were included, covering a range of game-like
      interventions, all more or less mentioning design parameters aimed at transfer.
      We found 9 studies where first-class transfer was part of the design of the
      intervention. In total, 8 studies dealt with transfer concepts and fidelity types
      in game-like intervention design in general; 3 studies dealt with the concept of
      second-class transfer types and reported effects, and 2 of those recognized
      transfer as a design parameter. CONCLUSIONS: In studies on game-like
      interventions for health and health care, transfer is regarded as a desirable
      effect but not as a basic principle for design. None of the studies determined
      the second class of transfer or instances thereof, although in 3 cases a
      nonliteral transfer type was present. We also found that studies on game-like
      interventions for health do not elucidate design choices made and rarely provide
      design principles for future work. Games and simulations for health abundantly
      build upon the principles of first-class transfer, but the adoption of second
      class transfer types proves scarce. It is likely to be worthwhile to explore the
      possibilities of second-class transfer types, as they may considerably influence
      educational objectives in terms of future serious game design for health.

PMID- 29175814
TI  - Buurtzorg could work in the UK, but why must it fit into the existing system?

PMID- 29175815
TI  - Mother is awarded L9m for "wrongful birth" after GP error.

PMID- 29175813
TI  - Demands and Needs for Psycho-Oncological eHealth Interventions in Women With
      Cancer: Cross-Sectional Study.
AB  - BACKGROUND: Over the last decade, a growing body of studies regarding the
      application of eHealth and various digital interventions has been published and
      are widely used in the psycho-oncological care. However, the effectiveness of
      eHealth applications in psycho-oncological care is still questioned due to
      missing considerations regarding evidence-based studies on the demands and needs
      in cancer-affected patients. OBJECTIVE: This cross-sectional study aimed to
      explore the cancer-affected women's needs and wishes for psycho-oncological
      content topics in eHealth applications and whether women with cancer differ in
      their content topics and eHealth preferences regarding their experienced
      psychological burden. METHODS: Patients were recruited via an electronic online
      survey through social media, special patient Internet platforms, and patient
      networks (both inpatients and outpatients, University Hospital Tuebingen,
      Germany). Participant demographics, preferences for eHealth and psycho
      oncological content topics, and their experienced psychological burden of
      distress, quality of life, and need for psychosocial support were evaluated.
      RESULTS: Of the 1172 patients who responded, 716 were included in the study. The
      highest preference for psycho-oncological content topics reached anxiety, ability
      to cope, quality of life, depressive feelings, and adjustment toward a new life
      situation. eHealth applications such as Web-based applications, websites, blogs,
      info email, and consultation hotline were considered to be suitable to convey
      these content topics. Psychological burden did not influence the preference rates
      according to psycho-oncological content and eHealth applications. CONCLUSIONS:
      Psycho-oncological eHealth applications may be very beneficial for women with
      cancer, especially when they address psycho-oncological content topics like
      anxiety, ability to cope, depressive feelings, self-esteem, or adjustment to a
      new life situation. The findings of this study indicate that psycho-oncological
      eHealth applications are a promising medium to improve the psychosocial care and
      enhance individual disease management and engagement among women with cancer.

PMID- 29175816
TI  - TiO2 and ZrO2 in biomass conversion: why catalyst reduction helps.
AB  - Biomass refers to plant-based materials that are not used for food or feed. As an
      energy source, lignocellulosic biomass (lignin, cellulose and hemicellulose) can
      be converted into various forms of biofuel using thermal, chemical and
      biochemical methods. Chemical conversion implies the use of solid catalysts,
      usually oxide materials. In this context, reducible oxides are considered to be
      more active than non-reducible oxides. But why? Using density functional theory
      DFT + U calculations with the inclusion of dispersion forces, we describe the
      properties of anatase TiO2, a reducible oxide, and tetragonal ZrO2, a non
      reducible oxide, the (101) surfaces in this context. In particular, we focus on
      the role of surface reduction, either by direct creation of oxygen vacancies via
      O2 desorption, or by treatment in hydrogen. We show that the presence of reduced
      centres on the surface of titania or zirconia (either Ti3+ or Zr3+ ions, or
      oxygen vacancies) results in lower barriers and more stable intermediates in two
      key reactions in biomass catalytic conversion: ketonization of acetic acid
      (studied on ZrO2) and deoxygenation of phenol (studied on TiO2). We discuss the
      role of Ru nanoparticles in these processes, and in particular in favouring H2
      dissociation and hydrogen spillover, which results in hydroxylated surfaces. We
      suggest that H2O desorption from the hydroxylated surfaces may be a relevant
      mechanism for the regeneration of oxygen vacancies, in particular on low
      coordinated sites of oxide nanoparticles. Finally, we discuss the role of
      nanostructuring in favouring oxide reduction, by discussing the properties of
      ZrO2 nanoparticles of diameter of about 2 nm.This article is part of a discussion
      meeting issue 'Providing sustainable catalytic solutions for a rapidly changing
      world'.

PMID- 29175817
TI  - Producing membrane proteins one simulation at a time.
AB  - Integral membrane proteins are studied with a number of structural and
      biophysical techniques, many requiring protein overexpression to reach sufficient
      quantities. However, achievement of the overexpression of membrane proteins is
      not necessarily straightforward, and the mechanisms and factors that influence
      expression are not clearly understood. A new study has now broken through this
      uncertainty by demonstrating the capability of coarse-grained simulations of
      membrane protein insertion to predict protein expression levels in Escherichia
      coli.

PMID- 29175819
TI  - Decreased oxygen exposure during transportation of newborns.
AB  - Oxygen is the most common treatment for newborns in need of respiratory support.
      However, oxygen can cause tissue injury through reactive oxygen species
      formation, especially in premature infants with reduced antioxidant defences, and
      may result in short-term and long-term toxic effects in multiple organ systems.
      Although most hospitals have the capability to tightly control oxygen delivery to
      hospitalised neonates, in many circumstances, the need is overlooked during
      infant transport. Lack of awareness of harm or appropriate medical equipment
      invariably results in excessive oxygen exposure. We developed a quality
      improvement programme to decrease oxygen exposure to newborns during their
      transportation, thus improving patient safety and quality of care.

PMID- 29175818
TI  - Providing sustainable catalytic solutions for a rapidly changing world.

PMID- 29175820
TI  - Cutaneous Langerhans cell histiocytosis presenting in a neonate.

PMID- 29175821
TI  - Post-traumatic stress after PICU and corticosteroid use.
AB  - AIM: To examine the association between corticosteroid use in paediatric
      intensive care units (PICU) and subsequent symptoms of post-traumatic stress
      disorder (PTSD). METHODS: The subjects were children aged 8-16 years admitted to
      PICU with sepsis, meningoencephalitis (ME) and other disorders. Illness
      information was extracted from case notes; 3-6 months post discharge children
      completed a PTSD symptom questionnaire (eight-item Impact of Events Scale (IES
      8)) assessing intrusion and avoidance symptoms. Saliva samples were also
      collected for cortisol profile analysis. RESULTS: 53 children completed the IES-8
      questionnaires. 33 provided saliva samples. 19 (36%) received corticosteroids. In
      children with sepsis (n=15), corticosteroid use was associated with significantly
      lower PTSD intrusion symptom scores. There was a trend towards an association
      between corticosteroid use and lower evening cortisol levels. There was a
      comparable but weaker trend in children with ME. DISCUSSION: Corticosteroid use
      may be associated with fewer PTSD symptoms and lower evening cortisol levels
      following PICU admission in children with sepsis.

PMID- 29175822
TI  - Inflammatory bowel disease and cancer risk.

PMID- 29175823
TI  - Major bleeding disorders: diagnosis, classification, management and recent
      developments in haemophilia.
AB  - In this review, we outline the standard of care for children in the UK with the
      most common major bleeding disorder, haemophilia, and how exciting new
      developments in therapy have the potential for further improvements in quality of
      life and clinical outcome. The combination of comprehensive specialist medical
      care, safer factor concentrates, earlier introduction of prophylaxis and patient
      specific education has allowed the current generation of patients with
      haemophilia to grow into adulthood with excellent joint function, pursuing full
      time employment with a good quality of life. We are entering an exciting new
      phase in paediatric haemophilia as potentially life-changing products appear on
      the scene taking a step towards achieving better, easier and personalised
      prophylaxis.

PMID- 29175824
TI  - Patterns of pain over time among children with juvenile idiopathic arthritis.
AB  - OBJECTIVES: Pain is a very common symptom of juvenile idiopathic arthritis (JIA).
      Disease activity alone cannot explain symptoms of pain in all children,
      suggesting other factors may be relevant. The objectives of this study were to
      describe the different patterns of pain experienced over time in children with
      JIA and to identify predictors of which children are likely to experience ongoing
      pain. METHODS: This study used longitudinal-data from patients (aged 1-16 years)
      with new-onset JIA. Baseline and up to 5-year follow-up pain data from the
      Childhood Arthritis Prospective Study (CAPS) were used. A two-step approach was
      adopted. First, pain trajectories were modelled using a discrete mixture model.
      Second, multinomial logistic regression was used to determine the association
      between variables and trajectories. RESULTS: Data from 851 individuals were
      included (4 years, median follow-up). A three-group trajectory model was
      identified: consistently low pain (n=453), improved pain (n=254) and consistently
      high pain (n=144). Children with improved pain or consistently high pain differed
      on average at baseline from consistently low pain. Older age at onset, poor
      function/disability and longer disease duration at baseline were associated with
      consistently high pain compared with consistently low pain. Early increases in
      pain and poor function/disability were also associated with consistently high
      pain compared with consistently low pain. CONCLUSIONS: This study has identified
      routinely collected clinical factors, which may indicate those individuals with
      JIA at risk of poor pain outcomes earlier in disease. Identifying those at
      highest risk of poor pain outcomes at disease onset may enable targeted pain
      management strategies to be implemented early in disease thus reducing the risk
      of poor pain outcomes.

PMID- 29175825
TI  - Reconstruction of head impacts in FIS World Cup alpine skiing.
AB  - INTRODUCTION: Prior to the 2013/2014 season, the International Ski Federation
      (FIS) increased the helmet testing speed from 5.4 to 6.8 m/s for alpine downhill,
      super-G and giant slalom. Whether this increased testing speed reflects head
      impact velocities in real head injury situations on snow is unclear. We therefore
      investigated the injury mechanisms and gross head impact biomechanics in seven
      real head injury situations among World Cup (WC) alpine skiers. METHODS: We
      analysed nine head impacts from seven head injury videos from the FIS Injury
      Surveillance System, throughout nine WC seasons (2006-2015) in detail. We used
      commercial video-based motion analysis software to estimate head impact
      kinematics in two dimensions, including directly preimpact and postimpact, from
      broadcast video. The sagittal plane angular movement of the head was also
      measured using angle measurement software. RESULTS: In seven of nine head
      impacts, the estimated normal to slope preimpact velocity was higher than the
      current FIS helmet rule of 6.8 m/s (mean 8.1 (+/-SD 0.6) m/s, range 1.9+/-0.8 to
      12.1+/-0.4 m/s). The nine head impacts had a mean normal to slope velocity change
      of 9.3+/-1.0 m/s, range 5.2+/-1.1 to 13.5+/-1.3 m/s. There was a large change in
      sagittal plane angular velocity (mean 43.3+/-2.9 rad/s (range 21.2+/-1.5 to
      64.2+/-3.0 rad/s)) during impact. CONCLUSION: The estimated normal to slope
      preimpact velocity was higher than the current FIS helmet rule of 6.8 m/s in
      seven of nine head impacts.

PMID- 29175826
TI  - Cluster analysis of novel isometric strength measures produces a valid and
      evidence-based classification structure for wheelchair track racing.
AB  - BACKGROUND: The Para athletics wheelchair-racing classification system employs
      best practice to ensure that classes comprise athletes whose impairments cause a
      comparable degree of activity limitation. However, decision-making is largely
      subjective and scientific evidence which reduces this subjectivity is required.
      AIM: To evaluate whether isometric strength tests were valid for the purposes of
      classifying wheelchair racers and whether cluster analysis of the strength
      measures produced a valid classification structure. METHODS: Thirty-two
      international level, male wheelchair racers from classes T51-54 completed six
      isometric strength tests evaluating elbow extensors, shoulder flexors, trunk
      flexors and forearm pronators and two wheelchair performance tests-Top-Speed (0
      15 m) and Top-Speed (absolute). Strength tests significantly correlated with
      wheelchair performance were included in a cluster analysis and the validity of
      the resulting clusters was assessed. RESULTS: All six strength tests correlated
      with performance (r=0.54-0.88). Cluster analysis yielded four clusters with
      reasonable overall structure (mean silhouette coefficient=0.58) and large
      intercluster strength differences. Six athletes (19%) were allocated to clusters
      that did not align with their current class. While the mean wheelchair racing
      performance of the resulting clusters was unequivocally hierarchical, the mean
      performance of current classes was not, with no difference between current
      classes T53 and T54. CONCLUSIONS: Cluster analysis of isometric strength tests
      produced classes comprising athletes who experienced a similar degree of activity
      limitation. The strength tests reported can provide the basis for a new, more
      transparent, less subjective wheelchair racing classification system, pending
      replication of these findings in a larger, representative sample. This paper also
      provides guidance for development of evidence-based systems in other Para sports.

PMID- 29175827
TI  - Poor overall quality of clinical practice guidelines for musculoskeletal pain: a
      systematic review.
AB  - OBJECTIVES: Undertake a systematic critical appraisal of contemporary clinical
      practice guidelines (CPGs) for common musculoskeletal (MSK) pain conditions:
      spinal (lumbar, thoracic and cervical), hip/knee (including osteoarthritis) and
      shoulder. DESIGN: Systematic review of CPGs (PROSPERO number:
      CRD42016051653).Included CPGs were written in English, developed within the last
      5 years, focused on adults and described development processes. Excluded CPGs
      were for: traumatic MSK pain, single modalities (eg, surgery), traditional
      healing/medicine, specific disease processes (eg, inflammatory arthropathies) or
      those that required payment. DATA SOURCES AND METHOD OF APPRAISAL: Four
      scientific databases (MEDLINE, Embase, CINAHL and Physiotherapy Evidence
      Database) and four guideline repositories. The Appraisal of Guidelines for
      Research and Evaluation (AGREE) II instrument was used for critical appraisal.
      RESULTS: 4664 records were identified, and 34 CPGs were included. Most were for
      osteoarthritis (n=12) or low back pain (n=11), most commonly from the USA (n=12).
      The mean overall AGREE II score was 45% (SD=19.7). Lowest mean domain scores were
      for applicability (26%, SD=19.5) and editorial independence (33%, SD=27.5). The
      highest score was for scope and purpose (72%, SD=14.3). Only 8 of 34 CPGS were
      high quality: for osteoarthritis (n=4), low back pain (n=2), neck (n=1) and
      shoulder pain (n=1).

PMID- 29175828
TI  - Retrograde 3D rotational venography (3DRV) for venous sinus stent placement in
      idiopathic intracranial hypertension.
AB  - BACKGROUND: Dural venous sinus stenting has emerged as an effective and durable
      treatment for idiopathic intracranial hypertension (IIH). Improved visualization
      of the venous sinuses can improve stent placement. METHODS: We present two cases
      of IIH treated with venous sinus stenting in which retrograde three-dimensional
      rotational venography (3DRV) provided superior anatomical details of the venous
      sinuses for optimal sizing and positioning of stent. RESULTS: Comparison of pre
      stent 3DRV with post-stent contrast-enhanced flat panel detector CT allowed
      confirmation of stent placement and the result of stenosis dilation. CONCLUSION:
      This 3DRV technique provides precise visualization of venous sinus stenosis prior
      to stenting without the need for arterial cerebral angiography during the
      treatment course.

PMID- 29175830
TI  - Who won in the BMJ Awards South Asia 2017?

PMID- 29175829
TI  - Safety and effectiveness of the Low Profile Visualized Intraluminal Support (LVIS
      and LVIS Jr) devices in the endovascular treatment of intracranial aneurysms:
      results of the TRAIL multicenter observational study.
AB  - BACKGROUND AND PURPOSE: To evaluate the safety and effectiveness of the low
      profile braided intracranial stents called the Low Profile Visualized
      Intraluminal Support (LVIS) devices for stent-assisted coil embolization of wide
      necked intracranial aneurysms. MATERIALS AND METHODS: This was a prospective,
      multicenter, observational study of unruptured and ruptured intracranial
      aneurysms treated with the LVIS devices. Imaging and clinical data were
      independently analyzed respectively by CoreLab and Clinical Event Committee.
      Primary endpoints were clinical safety, effectiveness, and angiographic stability
      of the results at 6 and 18 months. RESULTS: Ten centers participated in the
      study; 102 patients were included and 90 patients (42.2% men, 57.8% women) were
      eventually analyzed, among which 27 (30.0%) had multiple aneurysms. Twenty-three
      (25.6%) were ruptured aneurysms, four of which (4.4%) were treated in the acute
      phase. One aneurysm was treated per patient; 92 LVIS and LVIS Jr devices were
      placed overall. The total aneurysm occlusion rate was 91.0% on immediate post
      procedure angiograms, which remained unchanged at 6-month follow-up and was 92.4%
      at 18-month follow-up. One patient (1.1%) underwent retreatment between 6 and 18
      months of follow-up. A modified Rankin score of 0 was documented for most cases
      immediately after the procedure (86.7%) and at 6-month (86.8%) and 18-month
      (83.3%) follow-up. The overall permanent morbidity rate at 18 months was 5.6% and
      the overall rate of events with sequelae related to the stent was 2.2%. The 18
      month procedure-related mortality rate was 3.3%. No patient was deemed to require
      retreatment at 18-month follow-up. CONCLUSION: The LVIS/LVIS Jr endovascular
      devices are safe and effective in the treatment of ruptured and unruptured
      intracranial aneurysms, with acceptable complication rates, very high immediate
      total occlusion rates, and stable angiographic results.

PMID- 29175831
TI  - The fourth wave of biocatalysis is approaching.
AB  - Biocatalysis has undergone a tremendous development in the past few years. A
      plethora of methods enable the rather rapid tailored-design of an enzyme for a
      targeted reaction such as asymmetric synthesis of a chiral building block by the
      combination of information from sequence and structure databases with modern
      molecular biology methods and high-throughput screening tools. Moreover, novel
      non-natural reactions could be implemented into protein scaffolds and new enzyme
      classes are emerging, both broadening the repertoire of reactions now available
      for organic synthesis. Furthermore, impressive examples of metabolic engineering
      the combination of several newly introduced reaction steps in a microbial host
      have been developed, paving the way for large-scale processes for both
      pharmaceuticals and bulk chemicals. This contribution highlights recent
      developments in this area and points out future challenges.This article is part
      of a discussion meeting issue 'Providing sustainable catalytic solutions for a
      rapidly changing world'.

PMID- 29175832
TI  - Rear-facing versus forward-facing child restraints: an updated assessment.
AB  - OBJECTIVES: The National Highway Traffic Safety Administration and the American
      Academy of Pediatrics recommend children be placed in rear-facing child restraint
      systems (RFCRS) until at least age 2. These recommendations are based on
      laboratory biomechanical tests and field data analyses. Due to concerns raised by
      an independent researcher, we re-evaluated the field evidence in favour of RFCRS
      using the National Automotive Sampling System Crashworthiness Data System (NASS
      CDS) database. METHODS: Children aged 0 or 1 year old (0-23 months) riding in
      either rear-facing or forward-facing child restraint systems (FFCRS) were
      selected from the NASS-CDS database, and injury rates were compared by seat
      orientation using survey-weighted chi2 tests. In order to compare with previous
      work, we analysed NASS-CDS years 1988-2003, and then updated the analyses to
      include all available data using NASS-CDS years 1988-2015. RESULTS: Years 1988
      2015 of NASS-CDS contained 1107 children aged 0 or 1 year old meeting inclusion
      criteria, with 47 of these children sustaining injuries with Injury Severity
      Score of at least 9. Both 0-year-old and 1-year-old children in RFCRS had lower
      rates of injury than children in FFCRS, but the available sample size was too
      small for reasonable statistical power or to allow meaningful regression
      controlling for covariates. CONCLUSIONS: Non-US field data and laboratory tests
      support the recommendation that children be kept in RFCRS for as long as
      possible, but the US NASS-CDS field data are too limited to serve as a strong
      statistical basis for these recommendations.

PMID- 29175833
TI  - Evaluation of an integrated multisector campaign to increase child helmet use in
      Vietnam.
AB  - OBJECTIVE: This study presents child helmet use before, during and after
      implementing the Vietnamese National Child Helmet Action Plan (NCHAP) and
      evaluates its effect on child helmet use. The NCHAP, an integrated multisector
      campaign, incorporated a wide-scale public awareness campaign, school-based
      interventions, increased police patrolling and enforcement, and capacity building
      and support to relevant government departments in target provinces. METHODS: In
      Vietnam's three largest cities, 100 schools in 20 districts were selected to
      monitor motorcycle helmet use behaviour. The effectiveness of the NCHAP was
      measured by unannounced, filmed observations of student motorcycle passengers and
      their adult drivers as they arrived or left their schools at four points.
      Baseline observations at each school were conducted in March 2014, with
      subsequent observations in April 2015, December 2015 and May 2016. RESULTS:
      Across the 84 218 observed students, student helmet prevalence increased from
      36.1% in March 2014 to 69.3% immediately after the initiation in April 2015.
      Subsequent observations in December 2015 and May 2016 showed a reduction and
      stabilisation of helmet use, with 49.8% and 56.9% of students wearing helmets,
      respectively. Helmet use in students was higher when adult drivers were also
      wearing helmets. CONCLUSIONS: Integrated multisectoral interventions between
      governments, civil society and the corporate sector that incorporate
      communications, school-based education, incentives for change and police
      enforcement have the potential to increase helmet use among children. Future
      integrated campaigns may be more effective with an increased focus on parents and
      other adult drivers given their potential influence on child helmet use.

PMID- 29175834
TI  - Reactivity of CO2 on the surfaces of magnetite (Fe3O4), greigite (Fe3S4) and
      mackinawite (FeS).
AB  - The growing environmental, industrial and commercial interests in understanding
      the processes of carbon dioxide (CO2) capture and conversion have led us to
      simulate, by means of density functional theory calculations, the application of
      different iron oxide and sulfide minerals to capture, activate and catalytically
      dissociate this molecule. We have chosen the {001} and {111} surfaces of the
      spinel-structured magnetite (Fe3O4) and its isostructural sulfide counterpart
      greigite (Fe3S4), which are both materials with the Fe cations in the 2+/3+ mixed
      valence state, as well as mackinawite (tetragonal FeS), in which all iron ions
      are in the ferrous oxidation state. This selection of iron-bearing compounds
      provides us with understanding of the effect of the composition, stoichiometry,
      structure and oxidation state on the catalytic activation of CO2 The largest
      adsorption energies are released for the interaction with the Fe3O4 surfaces,
      which also corresponds to the biggest conformational changes of the CO2 molecule.
      Our results suggest that the Fe3S4 surfaces are unable to activate the CO2
      molecule, while a major charge transfer takes place on FeS{111}, effectively
      activating the CO2 molecule. The thermodynamic and kinetic profiles for the
      catalytic dissociation of CO2 into CO and O show that this process is feasible
      only on the FeS{111} surface. The findings reported here show that these minerals
      show promise for future CO2 capture and conversion technologies, ensuring a
      sustainable future for society.This article is part of a discussion meeting issue
      'Providing sustainable catalytic solutions for a rapidly changing world'.

PMID- 29175835
TI  - Paediatric ovarian tumours and their associated cancer susceptibility syndromes.
AB  - Non-epithelial ovarian tumours are rare neoplasms that occasionally arise in
      childhood and adolescence. They can be associated with various cancer
      susceptibility syndromes. The morphological overlap seen across these tumours and
      their rarity can make the diagnosis challenging. In the case of an incorrect
      diagnosis, the underlying genetic susceptibility may be missed. In this review,
      we outline the genetic background of ovarian non-epithelial tumours arising in
      children, emphasizing the genes harbouring pathogenic germline variants
      associated with each tumour type. Specifically, juvenile granulosa cell tumours,
      Sertoli-Leydig cell tumours, sex cord tumours with annular tubules, Sertoli cell
      tumours, germ cell tumours and small cell carcinoma of the ovary of
      hypercalcaemic type are discussed in this review. For each tumour type, we detail
      the personal and family history features and the presenting characteristics of
      the ovarian tumour as well as the pathological features and molecular markers
      that point towards a cancer predisposition syndrome. Throughout, we stress the
      need for specialised pathological review in difficult cases.

PMID- 29175836
TI  - Two patients with MIRAGE syndrome lacking haematological features: role of
      somatic second-site reversion SAMD9 mutations.
AB  - BACKGROUND: Myelodysplasia, infection, restriction of growth, adrenal hypoplasia,
      genital phenotypes and enteropathy (MIRAGE) syndrome is a recently described
      congenital disorder caused by heterozygous SAMD9 mutations. The phenotypic
      spectrum of the syndrome remains to be elucidated. METHODS AND RESULTS: We
      describe two unrelated patients who showed manifestations compatible with MIRAGE
      syndrome, with the exception of haematological features. Leucocyte genomic DNA
      samples were analysed with next-generation sequencing and Sanger sequencing,
      revealing the patients to have two de novoSAMD9 mutations on the same allele
      (patient 1 p.[Gln695*; Ala722Glu] and patient 2 p.[Gln39*; Asp769Gly]). In
      patient 1, p.Gln695* was absent in genomic DNA extracted from hair follicles,
      implying that the non-sense mutation was acquired somatically. In patient 2, with
      the 46,XX karyotype, skewed X chromosome inactivation pattern was found in
      leucocyte DNA, suggesting monoclonality of cells in the haematopoietic system. In
      vitro expression experiments confirmed the growth-restricting capacity of the two
      missense mutant SAMD9 proteins that is a characteristic of MIRAGE-associated
      SAMD9 mutations. CONCLUSIONS: Acquisition of a somatic nonsense SAMD9 mutation in
      the cells of the haematopoietic system might revert the cellular growth
      repression caused by the germline SAMD9 mutations (ie, second-site reversion
      mutations). Unexpected lack of haematological features in the two patients would
      be explained by the reversion mutations.

PMID- 29175837
TI  - Integrating protein engineering with process design for biocatalysis.
AB  - Biocatalysis uses enzymes for chemical synthesis and production, offering
      selective, safe and sustainable catalysis. While today the majority of
      applications are in the pharmaceutical sector, new opportunities are arising
      every day in other industry sectors, where production costs become a more
      important driver. In the early applications of the technology, it was necessary
      to design processes to match the properties of the biocatalyst. With the advent
      of protein engineering, organic chemists started to develop and improve enzymes
      to suit their needs. Likewise in industry, although not widespread, a new
      paradigm was already implemented several years ago to engineer enzymes to suit
      process needs. Today, a new era is entered, where the effectiveness with which
      such integrated protein and process engineering is achieved becomes critical to
      implementation. In this paper, the development of a tool to improve the
      effectiveness of this approach is discussed, namely the use of target-setting
      based on process requirements, to guide the necessary protein engineering.This
      article is part of a discussion meeting issue 'Providing sustainable catalytic
      solutions for a rapidly changing world'.

PMID- 29175838
TI  - Comparison of two low-sensitivity urine pregnancy tests for confirming the
      success of early medical abortion.
AB  - BACKGROUND: We introduced a single-window low-sensitivity urine pregnancy test
      (LSPT) to replace a double-window LSPT (both 1000 IU hCG) for self-assessment of
      the outcome of early medical abortion (EMA) (<=63 days gestation) 2 weeks later.
      We wished to compare assessment of outcomes of EMA with each LSPT. METHODS: A
      retrospective review of the outcomes of EMA during 10 months' use of the double
      window LSPT and the subsequent 10 months' use of the single-window LSPT to
      compare (i) detection of ongoing pregnancies and (ii) false-positive and invalid
      results with each LSPT. RESULTS: 492 and 555 women self-assessed the outcome of
      their EMA with the double- and single-window LSPTs, respectively. Ongoing
      pregnancies were uncommon and occurred in 4/1047 women (0.4%). Two of these four
      women did not conduct a LSPT as they presented before the LSPT was due with scant
      bleeding or continuing pregnancy symptoms. False-positive LSPT results occurred
      in 6 (1.2%) and 19 (3.4%) double- and single-window LSPT tests, respectively
      (P=0.0244). Invalid results were reported in 18 (3.6%) and 6 (1.1%) of double-
      and single-window LSPT groups, respectively (P=0.01). CONCLUSION: The
      introduction of the single-window LSPT has not impacted on the detection of
      ongoing pregnancy or on contact with the service due to a positive or invalid
      LSPT. Services could consider use of either LSPT but should also place emphasis
      on informing women about the clinical signs and symptoms that suggest failed
      abortion.

PMID- 29175840
TI  - Pain and pain relief with intrauterine device insertion.

PMID- 29175842
TI  - Commentary on 'A qualitative analysis of women's explanations for changing
      contraception: the importance of non-contraceptive effects'.

PMID- 29175841
TI  - A randomised trial comparing pain and ease of use of two different stabilising
      forceps for insertion of intrauterine contraception.
AB  - BACKGROUND: Pain at intrauterine contraception (IUC) fitting may be a deterrent
      for women and any reduction in discomfort would be likely to be beneficial to
      both women and clinicians. AIM: This study investigated the associated pain and
      the ease of use of two different stabilising forceps at the time of IUC
      placement. DESIGN: Single-blinded randomised controlled trial. One hundred parous
      women aged 18-50 years who had undergone at least one vaginal delivery were
      recruited. SETTING: An integrated sexual health service in the North of England.
      METHODS: Women were randomised to the use of either a Littlewoods forceps or a
      single-toothed tenaculum forceps to stabilise the cervix at the time of IUC
      placement. Pain levels were measured at forceps application, IUC insertion, and 5
      and 10 minutes post-procedure using a visual analogue scale (VAS). A clinician
      graded ease of use of the forceps and any associated bleeding. Wilcoxon rank-sum
      tests were used to compare pain levels between the two forceps groups. Linear
      regression was used when adjusting for potential confounders. RESULTS: Mean VAS
      scores were similar at forceps application (p=0.52), IUC fitting (p=0.10) and at
      5 minutes (p=0.32). There was a statistical difference in the degree of pain
      experienced at 10 minutes in the tenaculum group (p=0.01). Physicians found both
      forceps easy to use and there was no difference in bleeding (p=0.49).
      CONCLUSIONS: Parous women who have had a vaginal delivery can be reassured that
      IUC fitting is well tolerated. Pain scores were not affected by the type of
      forceps used to stabilise the cervix at IUC placement. Both forceps investigated
      were easy to use.

PMID- 29175843
TI  - Diagnosing migraine.
AB  - Migraine is a common headache disorder, particularly in women. It usually starts
      during the teens and twenties, a time when many women are seeking contraception
      advice. Migraine without aura is the most prevalent type of migraine, affecting
      up to 70% of people with migraine, while the remainder experience attacks with
      and/or without aura. Aura is a phase of focal neurological symptoms, typically
      visual. An increasing body of evidence identifies aura as a marker of increased
      risk of ischaemic stroke and its presence is a contraindication to the use of
      combined hormonal contraception (CHC). However, aura is often confused with more
      generalised premonitory visual symptoms of migraine that may precede attacks of
      migraine with and without aura, which are not associated with stroke risk.
      Diagnostic confidence is needed so that CHC is not withheld unnecessarily.

PMID- 29175844
TI  - A very specific absence of focus? A patient's response to 'Diagnosing migraine'.

PMID- 29175845
TI  - Sex, drugs and self-control: why chemsex is fast becoming a public health
      concern.

PMID- 29175846
TI  - A chemsex crucible: the context and the controversy.

PMID- 29175848
TI  - Elizabeth (Libby) Wilson 1926-2016.

PMID- 29175847
TI  - Venting grief for vocational erosion.

PMID- 29175849
TI  - Venus.

PMID- 29175851
TI  - US healthcare company fires 69 employees for refusing flu vaccination.

PMID- 29175852
TI  - Editorial.

PMID- 29175850
TI  - From word models to executable models of signaling networks using automated
      assembly.
AB  - Word models (natural language descriptions of molecular mechanisms) are a common
      currency in spoken and written communication in biomedicine but are of limited
      use in predicting the behavior of complex biological networks. We present an
      approach to building computational models directly from natural language using
      automated assembly. Molecular mechanisms described in simple English are read by
      natural language processing algorithms, converted into an intermediate
      representation, and assembled into executable or network models. We have
      implemented this approach in the Integrated Network and Dynamical Reasoning
      Assembler (INDRA), which draws on existing natural language processing systems as
      well as pathway information in Pathway Commons and other online resources. We
      demonstrate the use of INDRA and natural language to model three biological
      processes of increasing scope: (i) p53 dynamics in response to DNA damage, (ii)
      adaptive drug resistance in BRAF-V600E-mutant melanomas, and (iii) the RAS
      signaling pathway. The use of natural language makes the task of developing a
      model more efficient and it increases model transparency, thereby promoting
      collaboration with the broader biology community.

PMID- 29175853
TI  - Performance of statistical process control methods for regional surgical site
      infection surveillance: a 10-year multicentre pilot study.
AB  - BACKGROUND: Traditional strategies for surveillance of surgical site infections
      (SSI) have multiple limitations, including delayed and incomplete outbreak
      detection. Statistical process control (SPC) methods address these deficiencies
      by combining longitudinal analysis with graphical presentation of data. METHODS:
      We performed a pilot study within a large network of community hospitals to
      evaluate performance of SPC methods for detecting SSI outbreaks. We applied
      conventional Shewhart and exponentially weighted moving average (EWMA) SPC charts
      to 10 previously investigated SSI outbreaks that occurred from 2003 to 2013. We
      compared the results of SPC surveillance to the results of traditional SSI
      surveillance methods. Then, we analysed the performance of modified SPC charts
      constructed with different outbreak detection rules, EWMA smoothing factors and
      baseline SSI rate calculations. RESULTS: Conventional Shewhart and EWMA SPC
      charts both detected 8 of the 10 SSI outbreaks analysed, in each case prior to
      the date of traditional detection. Among detected outbreaks, conventional
      Shewhart chart detection occurred a median of 12 months prior to outbreak onset
      and 22 months prior to traditional detection. Conventional EWMA chart detection
      occurred a median of 7months prior to outbreak onset and 14 months prior to
      traditional detection. Modified Shewhart and EWMA charts additionally detected
      several outbreaks earlier than conventional SPC charts. Shewhart and SPC charts
      had low false-positive rates when used to analyse separate control hospital SSI
      data. CONCLUSIONS: Our findings illustrate the potential usefulness and
      feasibility of real-time SPC surveillance of SSI to rapidly identify outbreaks
      and improve patient safety. Further study is needed to optimise SPC chart
      selection and calculation, statistical outbreak detection rules and the process
      for reacting to signals of potential outbreaks.

PMID- 29175854
TI  - Transportation characteristics associated with non-arrivals to paediatric clinic
      appointments: a retrospective analysis of 51 580 scheduled visits.
AB  - BACKGROUND: Prior work has not studied the effects of transportation
      accessibility and patient factors on clinic non-arrival. OBJECTIVES: Our
      objectives were: (1) to evaluate transportation characteristics and patient
      factors associated with clinic non-arrival, (2) to evaluate the comparability of
      bus and car drive time estimates, and (3) to evaluate the combined effects of
      transportation accessibility and income on scheduled appointment non-arrival.
      METHODS: We queried electronic administrative records at an urban general
      pediatrics clinic. We compared patient and transportation characteristics between
      arrivals and non-arrivals for scheduled appointments using multivariable
      modeling. RESULTS: There were 15 346 (29.8%) clinic non-arrivals. In separate car
      and bus multivariable models that controlled for patient and transit
      characteristics, we identified significant interactions between income and drive
      time, and clinic non-arrival. Patients in the lowest quartile of income who were
      also in the longest quartile of travel time by bus had an increased OR of clinic
      non-arrival compared with patients in the lowest quartile of income and shortest
      quartile of travel time by bus (1.55; P<0.01). Similarly, patients in the lowest
      quartile of income who were also in the longest quartile of travel time by car
      had an increased OR of clinic non-arrival compared with patients in the lowest
      quartile of income and shortest quartile of travel time by car (1.21,
      respectively; P<0.01). CONCLUSIONS: Clinic non-arrival is associated with the
      interaction of longer travel time and lower income.

PMID- 29175855
TI  - Increasing the use of patient decision aids in orthopaedic care: results of a
      quality improvement project.
AB  - OBJECTIVE: To integrate patient decision aid (DA) delivery to promote shared
      decision-making and provide more patient-centred care within an orthopaedic
      surgery department for treatment of hip and knee osteoarthritis, lumbar herniated
      disc and lumbar spinal stenosis. METHODS: Different strategies were used across
      three distinct phases to promote DA delivery. First, we used a quality
      improvement bonus to generate awareness and interest in the DAs among
      specialists. Second, we adapted the electronic referral management system to
      enable DA orders at referral to a specialist. Third, we engaged clinic staff and
      specialists to design workflows that promoted DA delivery. We tracked the number
      of patients who received a DA, who ordered the DA, and collected usage data from
      a subset of patients. Our target was to reach 60% of patients with DAs. RESULTS:
      In phase 1, 28% (43/155) of spine patients and 37% (114/308) of hip/knee patients
      received a DA. In phase 2, 54% (64/118) of spine referrals and 58% (189/324) of
      hip/knee referrals included a request to send a patient a DA. In phase 3, 56%
      (90/162) of spine patients and 69% (213/307) of hip/knee patients received a DA,
      significantly more than in phase 1 (P<0.0001). In phase 3, both more DAs were
      ordered by clinic staff compared with specialists (56% phase 3 vs 34% phase 1,
      P<0.001) and sent before the visit (74% phase 3 vs 17% phase 1, P<0.001).
      Patients were more likely to report reviewing the DA when delivered before the
      visit (63% before vs 50% after, P=0.005). CONCLUSION: DA implementation into
      clinic workflow is possible and facilitated by engagement of the entire care team
      and the support of health information technology.

PMID- 29175856
TI  - Effect of a population-level performance dashboard intervention on maternal
      newborn outcomes: an interrupted time series study.
AB  - OBJECTIVES: To assess the effect of the Maternal Newborn Dashboard on six key
      clinical performance indicators in the province of Ontario, Canada. DESIGN:
      Interrupted time series using population-based data from the provincial birth
      registry covering a 3-year period before implementation of the Dashboard and 2.5
      years after implementation (November 2009 through March 2015). SETTING: All
      hospitals in the province of Ontario providing maternal-newborn care (n=94).
      INTERVENTION: A hospital-based online audit and feedback programme. MAIN OUTCOME
      MEASURES: Rates of the six performance indicators included in the Dashboard.
      RESULTS: 2.5 years after implementation, the audit and feedback programme was
      associated with statistically significant absolute decreases in the rates of
      episiotomy (decrease of 1.5 per 100 women, 95% CI 0.64 to 2.39), induction for
      postdates in women who were less than 41 weeks at delivery (decrease of 11.7 per
      100 women, 95% CI 7.4 to 16.0), repeat caesarean delivery in low-risk women
      performed before 39 weeks (decrease of 10.4 per 100 women, 95% CI 9.3 to 11.5)
      and an absolute increase in the rate of appropriately timed group B streptococcus
      screening (increase of 2.8 per 100, 95% CI 2.2 to 3.5). The audit and feedback
      programme did not significantly affect the rates of unsatisfactory newborn
      screening blood samples or formula supplementation at discharge. No statistically
      significant effects were observed for the two internal control outcomes or the
      four external control indicators-in fact, two external control indicators
      (episiotomy and postdates induction) worsened relative to before implementation.
      CONCLUSION: An electronic audit and feedback programme implemented in maternal
      newborn hospitals was associated with clinically relevant practice improvements
      at the provincial level in the majority of targeted indicators.

PMID- 29175857
TI  - Contextual interference during adaptation to asymmetric split-belt treadmill
      walking results in transfer of unique gait mechanics.
AB  - When humans make errors in stepping during walking due to a perturbation, they
      may adapt their gait as a way to correct for discrepancies between predicted and
      actual sensory feedback. This study sought to determine if increased contextual
      interference during acquisition of a novel asymmetric gait pattern would change
      lower-limb mechanical strategies generalized to different walking contexts. Such
      knowledge could help to clarify the role of contextual interference in locomotor
      adaptation, and demonstrate potential use in future gait rehabilitation
      paradigms. One belt on a split-belt treadmill was driven at a constant velocity
      while the other was driven at changing velocities according to one of three
      practice paradigms: serial, random blocked, or random training. Subjects returned
      to complete one of two different transfer tests. Results indicate that during
      acquisition, random practice requires unique gait mechanics to adapt to a
      challenging walking environment. Also, results from one transfer test close to
      that of the acquisition experience did not seem to demonstrate any contextual
      interference effect. Finally, random blocked practice resulted in highly unique
      changes in step length symmetry on a second, more challenging, transfer test.
      This perhaps indicates that a moderate level of contextual interference causes
      unique locomotor generalization strategies.

PMID- 29175858
TI  - Gelsolin regulates proliferation, apoptosis and invasion in natural killer/T-cell
      lymphoma cells.
AB  - The expression of gelsolin (GSN) is abnormal in many cancers, including
      extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). However, the
      biological function of GSN and its mechanism in NKTCL remain unclear. We found
      that GSN overexpression significantly suppressed cell proliferation, colony
      formation and invasion, and promoted apoptosis of natural killer (NK) cell line
      YTS. Moreover, the upregulation of GSN significantly decreased the levels of PI3K
      and p-Akt. Interestingly, blocking the PI3K/Akt signaling pathway significantly
      inhibited cell proliferation and invasion and promoted apoptosis of YTS cells. In
      conclusion, our findings indicate that GSN can suppress cell proliferation and
      invasion and promote apoptosis of YTS cells, and the PI3K/Akt signaling pathway
      is likely to be involved in this process.

PMID- 29175860
TI  - High salinity conveys thermotolerance in the coral model Aiptasia.
AB  - The endosymbiosis between dinoflagellate algae of the genus Symbiodinium and
      stony corals provides the foundation of coral reef ecosystems. Coral bleaching,
      the expulsion of endosymbionts from the coral host tissue as a consequence of
      heat or light stress, poses a threat to reef ecosystem functioning on a global
      scale. Hence, a better understanding of the factors contributing to heat stress
      susceptibility and tolerance is needed. In this regard, some of the most
      thermotolerant corals live in particularly saline habitats, but possible effects
      of high salinity on thermotolerance in corals are anecdotal. Here we test the
      hypothesis that high salinity may lead to increased thermotolerance. We conducted
      a heat stress experiment at low, intermediate, and high salinities using a set of
      host-endosymbiont combinations of the coral model Aiptasia. As expected, all host
      endosymbiont combinations showed reduced photosynthetic efficiency and
      endosymbiont loss during heat stress, but the severity of bleaching was
      significantly reduced with increasing salinities for one of the host-endosymbiont
      combinations. Our results show that higher salinities can convey increased
      thermotolerance in Aiptasia, although this effect seems to be dependent on the
      particular host strain and/or associated symbiont type. This finding may help
      explain the extraordinarily high thermotolerance of corals in high salinity
      environments, such as the Red Sea and the Persian/Arabian Gulf, and provides
      novel insight regarding factors that contribute to thermotolerance. Since our
      results are based on a salinity effect in symbiotic sea anemones, it remains to
      be determined whether this salinity effect can also be observed in stony corals.

PMID- 29175859
TI  - Investigating trehalose synthesis genes after cold acclimation in the Antarctic
      nematode Panagrolaimus sp. DAW1.
AB  - Panagrolaimus sp. DAW1 is a freeze-tolerant Antarctic nematode which survives
      extensive intracellular ice formation. The molecular mechanisms of this extreme
      adaptation are still poorly understood. We recently showed that desiccation
      enhanced RNA interference (RNAi) soaking can be used in conjunction with
      quantitative polymerase chain reaction (qPCR) to screen for phenotypes associated
      with reduced expression of candidate genes in Panagrolaimus sp. DAW1. Here, we
      present the use of this approach to investigate the role of trehalose synthesis
      genes in this remarkable organism. Previous studies have shown that acclimating
      Panagrolaimus sp. DAW1 at 5 degrees C before freezing or desiccation
      substantially enhances survival. In this study, the expression of tps-2 and other
      genes associated with trehalose metabolism, as well as lea-1, hsp-70 and gpx-1,
      in cold-acclimated and non-acclimated nematodes was analyzed using qPCR. Pd-tps-2
      and Pd-lea-1 were significantly upregulated after cold acclimation, indicating an
      inducible expression in the cold adaptation of Panagrolaimus sp. DAW1. The role
      of trehalose synthesis genes in Panagrolaimus sp. DAW1 was further investigated
      by RNAi. Compared to the controls, Pd-tps-2a(RNAi)-treated and cold-acclimated
      nematodes showed a significant decrease in mRNA, but no change in trehalose
      content or freezing survival. The involvement of two other trehalose synthesis
      genes (tps-2b and gob-1) was also investigated. These findings provide the first
      functional genomic investigation of trehalose synthesis genes in the non-model
      organism Panagrolaimus sp. DAW1. The presence of several trehalose synthesis
      genes with different RNAi sensitivities suggests the existence of multiple backup
      systems in Panagrolaimus sp. DAW1, underlining the importance of this sugar in
      preparation for freezing.

PMID- 29175861
TI  - NGF reprograms metastatic melanoma to a bipotent glial-melanocyte neural crest
      like precursor.
AB  - Melanoma pathogenesis from normal neural crest-derived melanocytes is often fatal
      due to aggressive cell invasion throughout the body. The identification of
      signals that reprogram de-differentiated, metastatic melanoma cells to a less
      aggressive and stable phenotype would provide a novel strategy to limit disease
      progression. In this study, we identify and test the function of developmental
      signals within the chick embryonic neural crest microenvironment to reprogram and
      sustain the transition of human metastatic melanoma to a neural crest cell-like
      phenotype. Results reveal that co-culture of the highly aggressive and metastatic
      human melanoma cell line C8161 upregulate a marker of melanosome formation (Mart
      1) in the presence of embryonic day 3.5 chick trunk dorsal root ganglia. We
      identify nerve growth factor (NGF) as the signal within this tissue driving Mart
      1 re-expression and show that NGF receptors trkA and p75 cooperate to induce Mart
      1 re-expression. Furthermore, Mart-1 expressing C8161 cells acquire a gene
      signature of poorly aggressive C81-61 cells. These data suggest that targeting
      NGF signaling may yield a novel strategy to reprogram metastatic melanoma toward
      a benign cell type.

PMID- 29175862
TI  - Competitive pressures affect sexual signal complexity in Kurixalus odontotarsus:
      insights into the evolution of compound calls.
AB  - Male-male vocal competition in anuran species is critical for mating success;
      however, it is also energetically demanding and highly time-consuming. Thus, we
      hypothesized that males may change signal elaboration in response to competition
      in real time. Male serrate-legged small treefrogs (Kurixalus odontotarsus)
      produce compound calls that contain two kinds of notes, harmonic sounds called 'A
      notes' and short broadband sounds called 'B notes'. Using male evoked vocal
      response experiments, we found that competition influences the temporal structure
      and complexity of vocal signals produced by males. Males produce calls with a
      higher ratio of notes:call, and more compound calls including more A notes but
      fewer B notes with contest escalation. In doing so, males minimize the energy
      costs and maximize the benefits of competition when the level of competition is
      high. This means that the evolution of sexual signal complexity in frogs may be
      susceptible to selection for plasticity related to adjusting performance to the
      pressures of competition, and supports the idea that more complex social contexts
      can lead to greater vocal complexity.

PMID- 29175863
TI  - Prognosis of immune-tolerant phase chronic hepatitis B.

PMID- 29175864
TI  - Investigating associations between the built environment and physical activity
      among older people in 20 UK towns.
AB  - BACKGROUND: Policy initiatives such as WHO Age Friendly Cities recognise the
      importance of the urban environment for improving health of older people, who
      have both low physical activity (PA) levels and greater dependence on local
      neighbourhoods. Previous research in this age group is limited and rarely uses
      objective measures of either PA or the environment. METHODS: We investigated the
      association between objectively measured PA (Actigraph GT3x accelerometers) and
      multiple dimensions of the built environment, using a cross-sectional multilevel
      linear regression analysis. Exposures were captured by a novel foot-based audit
      tool that recorded fine-detail neighbourhood features relevant to PA in older
      adults, and routine data. RESULTS: 795 men and 638 women aged 69-92 years from
      two national cohorts, covering 20 British towns, were included in the analysis.
      Median time in moderate to vigorous PA (MVPA) was 27.9 (lower quartile: 13.8,
      upper quartile: 50.4) minutes per day. There was little evidence of associations
      between any of the physical environmental domains (eg, road and path quality
      defined by latent class analysis; number of bus stops; area aesthetics; density
      of shops and services; amount of green space) and MVPA. However, analysis of area
      level income deprivation suggests that the social environment may be associated
      with PA in this age group. CONCLUSIONS: Although small effect sizes cannot be
      discounted, this study suggests that older individuals are less affected by their
      local physical environment and more by social environmental factors, reflecting
      both the functional heterogeneity of this age group and the varying nature of
      their activity spaces.

PMID- 29175865
TI  - Longitudinal analysis of cardiovascular disease risk profile in neighbourhood
      poverty subgroups: 5-year results from an afterschool fitness programme in the
      USA.
AB  - BACKGROUND: The WHO calls for affordable population-based prevention strategies
      for reducing the global burden of cardiovascular disease (CVD) on morbidity and
      mortality; however, effective, sustainable and accessible community-based
      approaches for CVD prevention in at-risk youth have yet to be identified. We
      examined the effects of implementing a daily park-based afterschool fitness
      programme on youth CVD risk profiles over 5 years and across area poverty
      subgroups. METHODS: The study included 2264 youth (mean age 9.4 years, 54% male,
      50% Hispanic, 47% non-Hispanic black, 70% high/very high area poverty) in Miami,
      Florida, USA. We used three-level repeated measures mixed models to determine the
      longitudinal effects of programme participation on modifiable CVD outcomes (2010
      2016). RESULTS: Duration of programme participation was significantly associated
      with CVD risk profile improvements, including body mass index (BMI) z-score,
      diastolic/systolic blood pressure, skinfold thicknesses, waist-hip ratio, sit
      ups, push-ups, Progressive Aerobic Cardiovascular Endurance Run (PACER) score,
      400 m run time, probability of developing systolic/diastolic hypertension and
      overweight/obesity in high/very high poverty neighbourhoods (P<0.001). Diastolic
      blood pressure decreased 3.4 percentile points (95% CI -5.85 to -0.85), 8.1
      percentile points (95% CI -11.98 to -4.26), 6.1 percentile points (95% CI -11.49
      to -0.66), 7.6 percentile points (95% CI -15.33 to -0.15) and 11.4 percentile
      points (95% CI -25.32 to 2.61) for 1-5 years, respectively, in high/very high
      poverty areas. In contrast, significant improvements were found only for PACER
      score and waist-hip ratio in low/mid poverty areas. CONCLUSION: This analysis
      presents compelling evidence demonstrating that park-based afterschool programmes
      can successfully maintain or improve at-risk youth CVD profiles over multiple
      years.

PMID- 29175866
TI  - Tackling Obesities: 10 years on.

PMID- 29175867
TI  - High percentage of undiagnosed HIV cases within a hyperendemic South African
      community: a population-based study.
AB  - BACKGROUND: Undiagnosed HIV infections could undermine efforts to reverse the
      global AIDS epidemic by 2030. In this study, we estimated the percentage of HIV
      positive persons who remain undiagnosed within a hyperendemic South African
      community. METHODS: The data come from a population-based surveillance system
      located in the Umkhanyakude district of the northern KwaZulu-Natal province,
      South Africa. We annually tested 38 661 adults for HIV between 2005 and 2016.
      Using the HIV-positive test results of 12 039 (31%) participants, we then back
      calculated the incidence of infection and derived the number of undiagnosed cases
      from this result. RESULTS: The percentage of undiagnosed HIV cases decreased from
      29.3% in 2005 to 15.8% in 2011. During this period, however, approximately 50% of
      the participants refused to test for HIV, which lengthened the average time from
      infection to diagnosis. Consequently, the percentage of undiagnosed HIV cases
      reversed direction and steadily increased from 16.1% to 18.9% over the 2012-2016
      period. CONCLUSIONS: Results from this hyperendemic South African setting show
      that the HIV testing rate is low, with long infection times, and an
      unsatisfactorily high percentage of undiagnosed cases. A high level of repeat HIV
      testing is needed to minimise the time from infection to diagnosis if the global
      AIDS epidemic is to be reversed within the next two decades.

PMID- 29175869
TI  - Metal-promoted titania photocatalysis for destruction of nitrates and organics
      from aqueous environments.
AB  - This review article provides an overview of activities in the rapidly developing
      field of water purification via photocatalytic methods and focuses on the removal
      of nitrate ions with simultaneous removal of the hole scavenger. Many of the
      issues associated with provision of potable water in the developing world may be
      resolved by the use of simple physical methodologies such as filtration. However,
      many of the issues associated with water purity in the developed world involve
      complex, stable molecules present at low concentrations that are nonetheless
      capable of producing toxic effects in plants and animals and that require more
      demanding removal technologies. Photocatalytic methods can be operated remotely
      and often show minimal production of undesired side products. Titania alone shows
      limitations, not only in terms of the slow rate of photoreduction of nitrate but
      also in terms of selectivity and the need to employ radiation in the UV region
      due to the magnitude of the band gap. Key challenges may be defined as: reducing
      the band gap/increasing absorption in the visible region, enhancing the
      adsorption capacity/access to the surface sites and reducing the rate of
      hole/electron recombination. The present article will focus on the use of titania
      based materials that involve metal co-catalysts for nitrate reduction.This
      article is part of a discussion meeting issue 'Providing sustainable catalytic
      solutions for a rapidly changing world'.

PMID- 29175868
TI  - Do socioeconomic inequalities in pain, psychological distress and oral health
      increase or decrease over the life course? Evidence from Sweden over 43 years of
      follow-up.
AB  - BACKGROUND: Inequalities over the life course may increase due to accumulation of
      disadvantage or may decrease because ageing can work as a leveller. We report how
      absolute and relative socioeconomic inequalities in musculoskeletal pain, oral
      health and psychological distress evolve with ageing. METHODS: Data were combined
      from two nationally representative Swedish panel studies: the Swedish Level-of
      Living Survey and the Swedish Panel Study of Living Conditions of the Oldest Old.
      Individuals were followed up to 43 years in six waves (1968, 1974, 1981,
      1991/1992, 2000/2002, 2010/2011) from five cohorts: 1906-1915 (n=899), 1925-1934
      (n=906), 1944-1953 (n=1154), 1957-1966 (n=923) and 1970-1981 (n=1199). The
      participants were 15-62 years at baseline. Three self-reported outcomes were
      measured as dichotomous variables: teeth not in good conditions, psychological
      distress and musculoskeletal pain. The fixed-income groups were: (A) never poor
      and (B) poor at least once in life. The relationship between ageing and the
      outcomes was smoothed with locally weighted ordinary least squares, and the
      relative and absolute gaps were calculated with Poisson regression using
      generalised estimating equations. RESULTS: All outcomes were associated with
      ageing, birth cohort, sex and being poor at least once in live. Absolute
      inequalities increased up to the age of 45-64 years, and then they decreased.
      Relative inequalities were large already in individuals aged 15-25 years, showing
      a declining trend over the life course. Selective mortality did not change the
      results. The socioeconomic gap was larger for current poverty than for being poor
      at least once in life. CONCLUSION: Inequalities persist into very old age, though
      they are more salient in midlife for all three outcomes observed.

PMID- 29175870
TI  - Non-thermal-plasma-activated de-NOx catalysis.
AB  - The combination of non-thermal plasma (NTP) with catalyst systems as an
      alternative technology to remove NOx emissions in the exhaust of lean-burn
      stationary and mobile sources is reviewed. Several factors, such as low exhaust
      gas temperatures (below 300 degrees C), low selectivity to N2 and the presence of
      impurities, make current thermally activated technologies inefficient. Various
      hybrid plasma-catalyst systems have been examined and shown to have a synergistic
      effect on de-NOx efficiency when compared with NTP or catalyst-alone systems. The
      NTP is believed to form oxygenated species, such as aldehydes and nitrogen
      containing organic species, and to convert NO to NO2, which improves the
      reduction efficiency of N2 during hydrocarbon-selective catalytic reduction
      reactions. The NTP has been used as a pretreatment to convert NO to its higher
      oxidation states such as NO2 to improve NOx reduction efficiency in the
      subsequent processes, e.g. NH3-selective catalytic reduction. It has been applied
      to the lean phase of the NOx storage to improve the adsorption capacity of the
      catalyst by conversion of NO to NO2 Alternatively, a catalyst with high
      adsorption capacity is chosen and the NTP is applied to the rich phase to improve
      the reduction activity of the catalyst at low temperature.This article is part of
      a discussion meeting issue 'Providing sustainable catalytic solutions for a
      rapidly changing world'.

PMID- 29175871
TI  - Structure and function of RET in multiple endocrine neoplasia type 2.
AB  - It has been twenty-five years since the discovery of oncogenic germline RET
      mutations as the cause of multiple endocrine neoplasia type 2 (MEN2). Intensive
      work over the last two and a half decades on RET genetics, signaling and cell
      biology has provided the current bases for the genotype-phenotype and functional
      correlations within this cancer syndrome. On the contrary, the structural and
      molecular basis for RET tyrosine kinase domain activation and oncogenic
      deregulation has remained largely elusive. Recent studies with a strong
      crystallographic and biochemical focus have started to elucidate key insights
      into such molecular and atomic details revealing unexpected and private
      mechanisms of actions and molecular determinants not previously envisioned. This
      review focuses on the structure and function of the RET receptor, and in
      particular, on what a more detailed view of the protein itself and what the
      current structural and molecular information tell us about the genotype and
      phenotype relationships in the cancer syndrome MEN2.

PMID- 29175872
TI  - Notch pathway inhibition targets chemoresistant insulinoma cancer stem cells.
AB  - Insulinomas (INS) are the most common neuroendocrine pancreatic tumours in humans
      and dogs. The long-term prognosis for malignant INS is still poor due to a low
      success rate of the current treatment modalities, particularly chemotherapy. A
      better understanding of the molecular processes underlying the development and
      progression of INS is required to develop novel targeted therapies. Cancer stem
      cells (CSCs) are thought to be critical for the engraftment and chemoresistance
      of many tumours, including INS. This study was aimed to characterise and target
      INS CSCs in order to develop novel targeted therapies. Highly invasive and
      tumourigenic human and canine INS CSC-like cells were successfully isolated.
      These cells expressed stem cell markers (OCT4, SOX9, SOX2, CD133 and CD34),
      exhibited greater resistance to 5-fluorouracil (5-FU) and demonstrated a more
      invasive and tumourigenic phenotype in vivo compared to bulk INS cells. Here, we
      demonstrated that Notch-signalling-related genes (NOTCH2 and HES1) were
      overexpressed in INS CSC-like cells. Protein analysis showed an active NOTCH2
      HES1 signalling in INS cell lines, especially in cells resistant to 5-FU.
      Inhibition of the Notch pathway, using a gamma secretase inhibitor (GSI),
      enhanced the sensitivity of INS CSC-like cells to 5-FU. When used in combination
      GSI and 5-FU, the clonogenicity in vitro and the tumourigenicity in vivo of INS
      CSC-like cells were significantly reduced. These findings suggested that the
      combined strategy of Notch signalling inhibition and 5-FU synergistically
      attenuated enriched INS CSC populations, providing a rationale for future
      therapeutic exploitation.

PMID- 29175873
TI  - Crowned dens syndrome.
AB  - Crowned dens syndrome is a rare presentation of calcium pyrophosphate deposition
      disease. It is characterised by severe occipital pain and neck stiffness. Acute
      presentations are typically accompanied by fever and an inflammatory response and
      hence can be misdiagnosed as polymyalgia rheumatica or meningitis. Chronic
      relapsing presentations may be misdiagnosed as cervicogenic neck pain or
      occipital neuralgia. We present a patient who presented with a chronic relapsing
      form of crowned dens syndrome and discuss the epidemiology, typical presentation
      and management of this eminently treatable condition.

PMID- 29175874
TI  - Psychiatric disease in an adolescent as a harbinger of cerebral X-linked
      adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (XALD) typically presents as a childhood cerebral
      demyelinating form, as an adult-onset adrenomyeloneuropathy or as adrenocortical
      insufficiency. Cerebral demyelination presenting in adolescence is unusual. We
      present an 17-year-old boy with adolescent-onset XALD initially manifesting with
      slowly progressive psychiatric symptoms. He was initially diagnosed with
      attention-deficit hyperactivity disorder and an acute psychosis. However, he was
      ultimately diagnosed with XALD based on his clinical course, neuroimaging
      findings and biochemical abnormalities. This case reiterates the atypical
      presentations of adolescent-onset cerebral XALD that may go unrecognised and
      misdiagnosed as a neurodevelopmental or psychiatric disease. Treatments for
      cerebral ALD are potentially life-saving, particularly when given early in the
      disease course.

PMID- 29175875
TI  - Late diagnosis of homocystinuria in an adult after extensive cerebral venous
      thrombosis.

PMID- 29175876
TI  - What we can learn from global emergency medicine.

PMID- 29175878
TI  - Ionised calcium levels in major trauma patients who received blood en route to a
      military medical treatment facility.
AB  - BACKGROUND: Hypocalcaemia is a common metabolic derangement in critically ill
      patients. Blood transfusion can also contribute to depleted calcium levels. The
      aims of this study were to identify the incidence of hypocalcaemia in military
      trauma patients receiving blood products en route to a deployed hospital facility
      and to determine if intravenous calcium, given during the prehospital phase, has
      an effect on admission calcium levels. METHODS: This was a retrospective review
      of patients transported by the UK Medical Emergency Response Team in Afghanistan
      between January 2010 and December 2014 who were treated with blood products in
      the prehospital setting. Total units of blood products administered, basic
      demographics, Injury Severity Score and trauma type were collected. Ionised serum
      calcium levels on admission to hospital were compared between those who received
      blood products without prehospital intravenous calcium supplemental therapy (non
      treatment) and patients who were treated with 10 mL of intravenous calcium
      chloride (10%) concurrently with blood products (treatment). RESULTS: The study
      included 297 patients; 237 did not receive calcium and 60 did. The incidence of
      hypocalcaemia in the non-treatment group was 70.0% (n=166) compared with 28.3%
      (n=17) in the treatment group. Serum calcium levels were significantly different
      between the groups (1.03 mmol/L vs 1.25 mmol/L, difference 0.22 mmol/L, 95% CI
      0.15 to 0.27). In the non-treatment group, 26.6% (n=63) had calcium levels within
      the normal range compared with 41.7% (n=25) in those who received calcium. There
      was a dose response of calcium level to blood products with a significant
      decrease in calcium levels as the volume of blood products increased. CONCLUSION:
      Trauma patients who received blood products were at high risk of hypocalcaemia.
      Aggressive management of these patients with intravenous calcium during
      transfusion may be required.

PMID- 29175877
TI  - The feasibility of an interactive voice response system (IVRS) for monitoring
      patient safety after discharge from the ED.
AB  - BACKGROUND: Return ED visits are frequent and may be due to adverse events:
      adverse outcomes related to healthcare received. An interactive voice response
      system (IVRS) is a technology that translates human telephone input into digital
      data. Use of IVRS has been explored in many healthcare settings but to a limited
      extent in the ED. We determined the feasibility of using an IVRS to assess for
      adverse events after ED discharge. METHODS: This before and after study assessed
      detection of adverse events among consecutive high-acuity patients discharged
      from a tertiary care ED pre-IVRS and post-IVRS over two 2-week periods. The IVRS
      asked if the patient was having a health problem and if they wanted to speak to a
      nurse. Patients responding yes received a telephone interview. We searched health
      records for deaths, admissions to hospital and return ED visits. Three trained
      emergency physicians independently determined adverse event occurrence. We
      analysed the data using descriptive statistics. RESULTS: Of 968 patients studied,
      patients' age, sex, acuity and presenting complaint were comparable pre-IVRS and
      post-IVRS. Postimplementation, 393 (81.7%) of 481 patients had successful IVRS
      contact. Of these, 89 (22.6%) wanted to speak to a nurse. A total of 37 adverse
      events were detected over the two periods: 10 patients with 10 (6.5%) adverse
      events pre-IVRS and 16 patients with 27 (16.9%) adverse events post-IVRS. In the
      postimplementation period, the adverse events of seven patients were detected by
      the IVRS and five patients spontaneously requested assistance navigating post-ED
      care. CONCLUSIONS: This was a successful proof-of-concept study for applying IVRS
      technology to assess patient safety issues for discharged high-acuity ED
      patients.

PMID- 29175879
TI  - Time is brain: An online controlling of traffic lights can save lives.

PMID- 29175880
TI  - US guidelines for the prevention of peanut allergy 2017.

PMID- 29175881
TI  - Sing Your Heart Out: community singing as part of mental health recovery.
AB  - This paper reports on a qualitative evaluation of a Norfolk-based network of
      community singing workshops aimed at people with mental health conditions and the
      general public. The aims of the study were (a) to evaluate the effectiveness of
      the Sing Your Heart Out (SYHO) project and (b) to identify the key features which
      made the project distinctive. The study draws on 20 interviews with participants,
      two focus groups with organisers and workshop leaders, and participative
      observation over a 6-month period. Interviewees all reported improvement in or
      maintenance of their mental health and well-being as a direct result of
      engagement in the singing workshops. For most it was a key component, and for
      some the only and sufficient component in their recovery and ongoing
      psychological stability. SYHO was regarded as different from choirs and from most
      other social groups and also different from therapy groups, music or otherwise.
      The combination of singing with an inclusive social aspect was regarded as
      essential in effecting recovery. The lack of pressure to discuss their condition
      and the absence of explicit therapy was also mentioned by most participants as an
      important and welcome element in why SYHO worked for them. The combination of
      singing and social engagement produced an ongoing feeling of belonging and well
      being. Attendance provided them with structure, support and contact that improved
      functioning and mood. We conclude that the SYHO model offers a low-commitment,
      low-cost tool for mental health recovery within the community.

PMID- 29175882
TI  - Evidence and speculation: reimagining approaches to architecture and research
      within the paediatric hospital.
AB  - As the dominant research paradigm within the construction of contemporary
      healthcare facilities, evidence-based design (EBD) will increasingly impact our
      expectations of what hospital architecture should be. Research methods within EBD
      focus on prototyping incremental advances and evaluating what has already been
      built. Yet medical care is a rapidly evolving system; changes to technology,
      workforce composition, patient demographics and funding models can create rapid
      and unpredictable changes to medical practice and modes of care. This dynamism
      has the potential to curtail or negate the usefulness of current best practice
      approaches. To imagine new directions for the role of the hospital in society, or
      innovative ways in which the built environment might support well-being, requires
      a model that can project beyond existing constraints. Speculative design employs
      a design-based research methodology to imagine alternative futures and uses the
      artefacts created through this process to enable broader critical reflection on
      existing practices. This paper examines the contribution of speculative design
      within the context of the paediatric hospital as a means of facilitating critical
      reflection regarding the design of new healthcare facilities. While EBD is
      largely limited by what has already been built, speculative design offers a
      complementary research method to meet this limitation.

PMID- 29175883
TI  - Smoking prevalence and attitudes towards smoking among Estonian physicians:
      results from cross-sectional studies in 2002 and 2014.
AB  - OBJECTIVES: To explore smoking prevalence and attitudes towards smoking among
      Estonian physicians in 2002 and 2014. DESIGN: Two self-administered cross
      sectional postal surveys were conducted among practising physicians in Estonia.
      PARTICIPANTS: Initial sample consisted of all practising physicians in Estonia.
      The corrected response rate was 67.8% in 2002 and 53.1% in 2014. Present study
      sample was restricted to physicians younger than 65 years (n=2549 in 2002, n=2339
      in 2014). METHODS: Age-standardised prevalence of smoking and prevalence of
      agreement with seven statements concerning attitudes towards smoking was
      determined. To analyse association of physicians' attitudes towards smoking with
      study year and smoking status, logistic regression analysis was used. Adjusted
      ORs of agreement with the seven statements were determined. Corresponding 95% CIs
      were calculated. RESULTS: The age-standardised prevalence of current smoking
      among men was 26.8% in 2002 and 15.3% in 2014, among women 10.4% and 5.8%,
      respectively. Compared with the year 2002, in 2014, prevalence of agreement with
      statements declaring harmfulness of smoking was higher and prevalence of
      agreement with statements approving smoking was lower. Adjusted ORs showed that
      compared with 2002, physicians' attitudes towards smoking were less favourable in
      2014, and physicians' attitudes towards smoking were associated with their
      smoking status. CONCLUSIONS: Compared with 2002, the age-standardised smoking
      prevalence among male and female physicians was lower, and attitudes towards
      smoking were less approving in 2014. The smoking physicians had more approving
      attitudes towards smoking than their non-smoking colleagues.

PMID- 29175884
TI  - Epidemiology of obesity and overweight in sub-Saharan Africa: a protocol for a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Globally, overweight and obesity were estimated to cause 3.4
      million deaths, 3.9% of years of life lost and 3.8% of disability-adjusted life
      years in 2010. Despite the fact that obesity and overweight is a problem of high
      income countries, low- and middle-income countries (LMICs), in particular urban
      settings of sub-Saharan African countries, face the challenge of an increasing
      trend. The aim of this systematic review and meta-analysis will be to determine
      the prevalence of obesity and overweight individuals in sub-Saharan Africa and to
      help guide policy planners in the decision-making process for the increase in non
      communicable diseases in Africa. METHODS AND ANALYSES: A comprehensive systematic
      review and meta-analysis of published studies on the prevalence of obesity and
      overweight in sub-Saharan Africa will be conducted. A computerised internet
      search using Medline/PubMed, Google Scholar and EMBASE databases and reference
      lists of previous prevalence studies and detailed search strategy and cross
      checking of reference lists of published peer-reviewed articles will be conducted
      to identify all epidemiological and/or clinical studies published in English and
      French. We will use the PRISMA (Preferred Reporting Items for Systematic reviews
      and Meta-Analyses) statement for reporting. The overall effect (pooled estimated
      effect size) of the prevalence of obesity and overweight will be analysed using
      the Der Simonian-Laird random effects meta-analysis (random effects model) and
      the obesity proportion (with 95% CI) will be measured. ETHICS AND DISSEMINATION:
      The underlying work is based on systematic reviews of published data and thus
      doed not require ethical review approval. The findings of the systematic review
      will be disseminated in different conferences and seminars and will be published
      in a reputable and refereed international peer-reviewed journal. PROSPERO
      REGISTRATION NUMBER: CRD42017064942.

PMID- 29175885
TI  - How effective is community physical activity promotion in areas of deprivation
      for inactive adults with cardiovascular disease risk and/or mental health
      concerns? Study protocol for a pragmatic observational evaluation of the 'Active
      Herts' physical activity programme.
AB  - INTRODUCTION: There is a high prevalence of inactive adults in the UK, and many
      suffer from conditions such as cardiovascular disease (CVD) or poor mental
      health. These coexist more frequently in areas of higher socioeconomic
      deprivation. There is a need to test the effectiveness, acceptability and
      sustainability of physical activity programmes. Active Herts uses novel evidence
      based behaviour change techniques to target physical inactivity. METHODS AND
      ANALYSIS: Active Herts is a community physical activity programme for inactive
      adults aged 16+ with one or more risk factors for CVD and/or a mild to moderate
      mental health condition. This evaluation will follow a mixed-methods longitudinal
      (baseline, and 3-month, 6-month and 12-month follow-ups) design. Pragmatic
      considerations mean delivery of the programme differs by locality. In two areas
      programme users will receive a behaviour change technique booklet, regular
      consultations, a booster phone call, motivational text messages and signposting
      to 12 weeks of exercise classes. In another two areas programme users will also
      receive 12 weeks of free tailored exercise classes, with optional exercise
      'buddies' available. An outcome evaluation will assess changes in physical
      activity as the primary outcome, and sporting participation, sitting, well-being,
      psychological capability and reflective motivation as secondary outcomes. A
      process evaluation will explore the views of stakeholders, delivery staff and
      programme leads. Economic evaluation will examine the programme costs against the
      benefits gained in terms of reduced risk of morbidity. ETHICS AND DISSEMINATION:
      This study was been approved by the Faculty of Medicine and Health Sciences
      Research Ethics Committee at the University of East Anglia. Informed written
      consent will be obtained from programme users in the evaluation. Results will be
      published in peer-reviewed journals, presented at conferences, and shared through
      the study website and local community outlets. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov ID number: NCT03153098.

PMID- 29175886
TI  - Monitoring of clinical strains and environmental fungal aerocontamination to
      prevent invasive aspergillosis infections in hospital during large deconstruction
      work: a protocol study.
AB  - INTRODUCTION: Monitoring fungal aerocontamination is an essential measure to
      prevent severe invasive aspergillosis (IA) infections in hospitals. One central
      block among 32 blocks of Edouard Herriot Hospital (EHH) was entirely demolished
      in 2015, while care activities continued in surrounding blocks. The main
      objective was to undertake broad environmental monitoring and clinical
      surveillance of IA cases to document fungal dispersion during major
      deconstruction work and to assess clinical risk. METHODS AND ANALYSIS: A daily
      environmental survey of fungal loads was conducted in eight wards located near
      the demolition site. Air was collected inside and outside selected wards by agar
      impact samplers. Daily spore concentrations were monitored continuously by
      volumetric samplers at a flow rate of 10 L.min-1. Daily temperature, wind
      direction and speed as well as relative humidity were recorded by the French
      meteorological station Meteociel. Aspergillus fumigatus strains stored will be
      genotyped by multiple-locus, variable-number, tandem-repeat analysis. Antifungal
      susceptibility will be assessed by E-test strips on Roswell Park Memorial
      Institute medium supplemented with agar. Ascertaining the adequacy of current
      environmental monitoring techniques in hospital is of growing importance,
      considering the rising impact of fungal infections and of curative antifungal
      costs. The present study could improve the daily management of IA risk during
      major deconstruction work and generate new data to ameliorate and redefine
      current guidelines. ETHICS AND DISSEMINATION: This study was approved by the
      clinical research and ethics committees of EHH.

PMID- 29175887
TI  - Impact of US smoke-free air laws on restaurants and bars by employer size: a
      panel study.
AB  - OBJECTIVES: Thirty states have smoke-free air laws that ban smoking in
      restaurants and bars, covering nearly two-thirds of the US population. It is well
      established that these laws generally have a null or positive economic impact on
      restaurants and bars. However, all establishments in a geographic area are
      usually treated as a homogeneous group without considering the potential for
      differential effects by establishment characteristics. This study uses variation
      in smoke-free air laws over time to estimate their impact on employment in
      restaurants and bars with a focus on potential differences by employer size
      (number of employees). A two-pronged approach with a national-level and state
      level analysis is used to take advantage of more granular data availability for a
      single state (North Carolina). DESIGN: Observational study using panel data.
      SETTING: 1) US, 2) North Carolina INTERVENTIONS: Smoke-free air laws. OUTCOME
      MEASURES: State-level accommodation and food services employment for all 50
      states and District of Columbia from 1990 through 2014 (Quarterly Census of
      Employment and Wages); county-level restaurant and bar employment in North
      Carolina from 2001 through 2014 (North Carolina Department of Commerce). RESULTS:
      There is no evidence of a redistributive effect of smoke-free air laws on
      restaurant and bar employment by employer size. CONCLUSION: The lack of a
      redistributive effect is an important finding for policy-makers considering
      implementation or expansion of a smoke-free air law to protect employees and
      patrons from the dangers of exposure to secondhand smoke.

PMID- 29175888
TI  - When has service provision for transient ischaemic attack improved enough? A
      discrete event simulation economic modelling study.
AB  - OBJECTIVES: The aim of this study was to examine the impact of transient
      ischaemic attack (TIA) service modification in two hospitals on costs and
      clinical outcomes. DESIGN: Discrete event simulation model using data from
      routine electronic health records from 2011. PARTICIPANTS: Patients with
      suspected TIA were followed from symptom onset to presentation, referral to
      specialist clinics, treatment and subsequent stroke. INTERVENTIONS: Included
      existing versus previous (less same day clinics) and hypothetical service
      reconfiguration (7-day service with less availability of clinics per day).
      OUTCOME MEASURES: The primary outcome of the model was the prevalence of major
      stroke after TIA. Secondary outcomes included service costs (including those of
      treating subsequent stroke) and time to treatment and attainment of national
      targets for service provision (proportion of high-risk patients (according to
      ABCD2 score) seen within 24 hours). RESULTS: The estimated costs of previous
      service provision for 490 patients (aged 74+/-12 years, 48.9% female and 23.6%
      high risk) per year at each site were L340 000 and L368 000, respectively. This
      resulted in 31% of high-risk patients seen within 24 hours of referral (47/150)
      with a median time from referral to clinic attendance/treatment of 1.15 days (IQR
      0.93-2.88). The costs associated with the existing and hypothetical services
      decreased by L5000 at one site and increased L21 000 at the other site. Target
      attainment was improved to 79% (118/150). However, the median time to clinic
      attendance was only reduced to 0.85 days (IQR 0.17-0.99) and thus no appreciable
      impact on the modelled incidence of major stroke was observed (10.7 per year, 99%
      CI 10.5 to 10.9 (previous service) vs 10.6 per year, 99% CI 10.4 to 10.8
      (existing service)). CONCLUSIONS: Reconfiguration of services for TIA is
      effective at increasing target attainment, but in services which are already
      working efficiently (treating patients within 1-2 days), it has little estimated
      impact on clinical outcomes and increased investment may not be worthwhile.

PMID- 29175889
TI  - The impact of approaches in improving male partner involvement in the prevention
      of mother-to-child transmission of HIV on the uptake of maternal antiretroviral
      therapy among HIV-seropositive pregnant women in sub-Saharan Africa: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: To identify the approaches that are used in improving on male partner
      involvement in the prevention of mother-to-child transmission (PMTCT) of HIV and
      their impact on the uptake maternal antiretroviral therapy (ART) in sub-Saharan
      Africa (SSA). SETTING: This was a systematic review and meta-analysis of
      published studies carried out in SSA at all levels of healthcare (primary,
      secondary, tertiary and community). PARTICIPANTS: The participants of the studies
      included were HIV-positive pregnant women and breastfeeding mothers with their
      male partners. Studies were included if they were conducted in SSA and mentioned
      an approach used in improving male partner involvement with data on the impact on
      the uptake of maternal ART uptake. OUTCOMES: In the protocol, maternal ART
      uptake, infant prophylaxis, safe infant feeding options, condom use and family
      planning were envisaged. However, only maternal ART has been reported here due to
      limitations on the word count. RESULTS: From an initial 2316 non-duplicate
      articles, 17 articles were included in the systematic review and meta-analysis.
      In the combined model, the ORs for complex community interventions, enhanced
      psychosocial interventions, verbal encouragement and invitation letters were 4.22
      (95% CI 2.27 to 7.77), 2.29 (95% CI 1.42 to 7.69), 2.39 (95% CI 1.26 to 4.53) and
      1.21 (95% CI 0.89 to 1.63), respectively, whereas in the model using adjusted
      ORs, enhanced psychosocial interventions had a higher effect than any other
      intervention. The heterogeneity was moderate using adjusted ORs. CONCLUSION:
      Enhanced psychosocial interventions and complex community interventions increase
      male partner involvement and the uptake of PMTCT services more than any other
      intervention. Invitation letters had no effect. More randomised trials and
      observational studies (that have adjusted for potential confounders) are needed
      in the future. PROSPERO REGISTRATION NUMBER: 42016032673.

PMID- 29175890
TI  - Is there an association between vitamin D status and risk of chronic low back
      pain? A nested case-control analysis in the Nord-Trondelag Health Study.
AB  - OBJECTIVES: To explore potential associations between vitamin D status and risk
      of chronic low back pain (LBP) in a Norwegian cohort, and to investigate whether
      relationships depend on the season of blood sample collection. DESIGN: A nested
      case-control study in a prospective data set. SETTING: The Norwegian community
      based Nord-Trondelag Health Study (HUNT). Data were collected in the HUNT2 (1995
      1997) and HUNT3 (2006-2008) surveys. MAIN OUTCOME MEASURE: Chronic LBP, defined
      as LBP persisting at least 3 months continuously during the past year.
      PARTICIPANTS: Among individuals aged 19-55 years without LBP in HUNT2, a data set
      was generated including 1685 cases with LBP in HUNT3 and 3137 controls without
      LBP. METHODS: Blood samples from the participants collected in HUNT2 were
      analysed for serum 25-hydroxyvitamin D (25(OH)D) level. Associations with LBP in
      HUNT3 were evaluated by unconditional logistic regression analysis with
      adjustment for age, sex, work status, physical activity at work and in leisure
      time, education, smoking, and body mass index. RESULTS: No association between
      vitamin D status and risk of chronic LBP was found in the total data set (OR per
      10 nmol/L 25(OH)D=1.01, 95% CI 0.97 to 1.06) or in individuals with blood samples
      collected in summer/autumn (OR per 10 nmol/L 25(OH)D=0.99, 95% CI 0.93 to 1.06).
      For blood samples drawn in winter/spring, associations differed significantly
      between women and men (p=0.004). Among women a positive association was seen (OR
      per 10 nmol/L 25(OH)D=1.11, 95% CI 1.02 to 1.20), but among men no significant
      association was observed (OR per 10 nmol/L 25(OH)D=0.90, 95% CI 0.81 to 1.01).
      CONCLUSIONS: Overall, no association between vitamin D status and risk of LBP was
      demonstrated. The association suggested in women for the winter/spring season
      cannot be regarded as established.

PMID- 29175891
TI  - Self-management of cardiac pain in women: an evidence map.
AB  - OBJECTIVE: To describe the current evidence related to the self-management of
      cardiac pain in women using the process and methodology of evidence mapping.
      DESIGN AND SETTING: Literature search for studies that describe the self
      management of cardiac pain in women greater than 18 years of age, managed in
      community, primary care or outpatient settings, published in English or a
      Scandinavian language between 1 January 1990 and 24 June 2016 using AMED, CINAHL,
      ERIC, EMBASE, MEDLINE, Proquest, PsychInfo, the Cochrane Library, Scopus,
      Swemed+, Web of Science, the Clinical Trials Registry, International Register of
      Controlled Trials, MetaRegister of Controlled Trials, theses and dissertations,
      published conference abstracts and relevant websites using GreyNet International,
      ISI proceedings, BIOSIS and Conference papers index. Two independent reviewers
      screened using predefined eligibility criteria. Included articles were classified
      according to study design, pain category, publication year, sample size, per cent
      women and mean age. INTERVENTIONS: Self-management interventions for cardiac pain
      or non-intervention studies that described views and perspectives of women who
      self-managed cardiac pain. PRIMARY AND SECONDARY OUTCOMES MEASURES: Outcomes
      included those related to knowledge, self-efficacy, function and health-related
      quality of life. RESULTS: The literature search identified 5940 unique articles,
      of which 220 were included in the evidence map. Only 22% (n=49) were intervention
      studies. Sixty-nine per cent (n=151) of the studies described cardiac pain
      related to obstructive coronary artery disease (CAD), 2% (n=5) non-obstructive
      CAD and 15% (n=34) postpercutaneous coronary intervention/cardiac surgery. Most
      were published after 2000, the median sample size was 90 with 25%-100% women and
      the mean age was 63 years. CONCLUSIONS: Our evidence map suggests that while much
      is known about the differing presentations of obstructive cardiac pain in middle
      aged women, little research focused on young and old women, non-obstructive
      cardiac pain or self-management interventions to assist women to manage cardiac
      pain. PROSPERO REGISTRATION NUMBER: CRD42016042806.

PMID- 29175892
TI  - Interrupted versus continuous suturing for vesicourethral anastomosis during
      radical prostatectomy: protocol for a systematic review and meta-analysis.
AB  - INTRODUCTION: Radical prostatectomy is the mainstay of treatment for prostate
      cancer. The vesicourethral anastomosis is a critical step, which most likely
      impacts urinary continence and urethral stenosis. To date, it still remains
      unclear whether interrupted and continuous suturing for the anastomosis have
      different outcomes. Therefore, the aim of this systematic review and meta
      analysis is to compare different suture techniques for vesicourethral anastomosis
      in terms of surgical and functional parameters. METHODS AND ANALYSIS: A
      comprehensive literature search will be conducted covering MEDLINE, Embase, Web
      of Science, the Cochrane Central Register of Controlled Trials and
      ClinicalTrials.gov. Studies comparing interrupted versus continuous suturing will
      be included in the analyses. No language restrictions will be applied. Screening,
      data extraction, statistical analysis and reporting will be done in line with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines. Quality assessment will be performed with the help of the Cochrane
      Collaboration's tool for assessing risk of bias and the Newcastle-Ottawa Scale
      for assessing quality of non-randomised studies. The quality of evidence will be
      evaluated with the Grading of Recommendations Assessment, Development and
      Evaluation. The primary outcome will be the time until removal of the urinary
      catheter. Secondary outcomes include rate of extravasation, length of hospital
      stay, time needed to perform the anastomosis, continence level at defined
      postoperative intervals and development of urethral strictures. Quantitative
      analysis will be calculated if meaningful. ETHICS AND DISSEMINATION: In order to
      meet the highest ethical and methodological standards. we followed the PRISMA
      Protocol 2015 checklist. Each item was answered appropriately. For systematic
      reviews the ethical issues are strictly methodological as only data that were
      published earlier will be used. The full manuscript will be submitted to a peer
      reviewed journal. Furthermore, the results will be presented on national and
      international congresses. TRIAL REGISTRATION NUMBER: International prospective
      register of systematic reviews PROSPERO CRD42017076126.

PMID- 29175893
TI  - Oral corticosteroid dosing regimen and long-term prognosis in generalised
      myasthenia gravis: a multicentre cross-sectional study in Japan.
AB  - OBJECTIVE: We examined the correlation between the dosing regimen of oral
      prednisolone (PSL) and the achievement of minimal manifestation status or better
      on PSL <=5 mg/day lasting >6 months (the treatment target) in patients with
      generalised myasthenia gravis (MG). METHODS: We classified 590 patients with
      generalised MG into high-dose (n=237), intermediate-dose (n=187) and low-dose
      (n=166) groups based on the oral PSL dosing regimen, and compared the clinical
      characteristics, previous treatments other than PSL and prognosis between three
      groups. The effect of oral PSL dosing regimen on the achievement of the treatment
      target was followed for 3 years of treatment. RESULTS: To achieve the treatment
      target, ORs for low-dose versus high-dose regimen were 10.4 (P<0.0001) after 1
      year of treatment, 2.75 (P=0.007) after 2 years and 1.86 (P=0.15) after 3 years;
      and those for low-dose versus intermediate-dose regimen were 13.4 (P<0.0001)
      after 1 year, 3.99 (P=0.0003) after 2 years and 4.92 (P=0.0004) after 3 years.
      Early combined use of fast-acting treatment (OR: 2.19 after 2 years, P=0.02; OR:
      2.11 after 3 years, P=0.04) or calcineurin inhibitors (OR: 2.09 after 2 years,
      P=0.03; OR: 2.36 after 3 years, P=0.02) was associated positively with
      achievement of treatment target. CONCLUSION: A low-dose PSL regimen with early
      combination of other treatment options may ensure earlier achievement of the
      treatment target in generalised MG.

PMID- 29175894
TI  - Mediterranean fever gene mutations in patients with possible neuro-Sweet disease:
      a case series.

PMID- 29175895
TI  - Acute-onset chronic inflammatory demyelinating polyneuropathy after Zika virus
      infection.

PMID- 29175896
TI  - Clinical course of MOG antibody-associated recurrent demyelinating diseases.

PMID- 29175897
TI  - Compulsive sexual behaviour in Parkinson's disease is associated with higher
      doses of levodopa.

PMID- 29175898
TI  - Limb girdle muscular dystrophy due to mutations in POMT2.
AB  - BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2
      (POMT2) are known to cause severe congenital muscular dystrophy, and recently,
      mutations in POMT2 have also been linked to a milder limb-girdle muscular
      dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four cases have
      been reported so far.ClinicalTrials.gov ID: NCT02759302 METHODS: We report 12 new
      cases of LGMD2N, aged 18-63 years. Muscle involvement was assessed by MRI, muscle
      strength testing and muscle biopsy analysis. Other clinical features were also
      recorded. RESULTS: Presenting symptoms were difficulties in walking, pain during
      exercise, delayed motor milestones and learning disabilities at school. All had
      some degree of cognitive impairment. Brain MRIs were abnormal in 3 of 10
      patients, showing ventricular enlargement in one, periventricular
      hyperintensities in another and frontal atrophy of the left hemisphere in a third
      patient. Most affected muscle groups were hip and knee flexors and extensors on
      strength testing. On MRI, most affected muscles were hamstrings followed by
      paraspinal and gluteal muscles. The 12 patients in our cohort carried 11 alleles
      with known mutations, whereas 11 novel mutations accounted for the remaining 13
      alleles. CONCLUSION: We describe the first cohort of patients with LGMD2N and
      show that unlike other LGMD types, all patients had cognitive impairment. Primary
      muscle involvement was found in hamstring, paraspinal and gluteal muscles on MRI,
      which correlated well with reduced muscle strength in hip and knee flexors and
      extensors. The study expands the mutational spectrum for LGMD2N, with the
      description of 11 novel POMT2 mutations in the association with LGMD2N. CLINICAL
      TRIAL REGISTRATION: NCT02759302.

PMID- 29175899
TI  - Prospective cohort study showing persistent HSV-2 shedding in women with genital
      herpes 2 years after acquisition.
AB  - OBJECTIVES: Herpes simplex virus type 2 (HSV-2) is a prevalent infection with
      great variability in clinical and virological manifestations among individuals.
      This prospective cohort study aims to evaluate the natural history of HSV-2
      reactivation in the genital area in the same group of women over time. METHODS:
      Eighteen immunocompetent HSV-2 seropositive women were evaluated for viral
      shedding for 70 consecutive days within a median of 8 months (range 1-24 months)
      of HSV-2 acquisition and again approximately 2.5 years later from the original
      study. Participants obtained daily swabs of genital secretions for HSV PCR and
      recorded genital symptoms. RESULTS: The viral shedding rate was 29% during the
      initial study and 19% in the follow-up study (32% reduction, P=0.019).
      Subclinical shedding rate also decreased from 24% to 13% (37% reduction,
      P=0.032), as did the rate of days with genital lesions from 22% to 15% (33%
      reduction, P=0.24). The mean copy number during viral shedding remained unchanged
      over time at 4.8 log10 c/mL (SD=2.0 and 1.6 during each study, respectively,
      P=0.33). Women with high viral shedding rates in the past were likely to continue
      to have high shedding rates (r=0.63, P=0.005). CONCLUSIONS: Despite some
      reduction, high viral shedding rates persist in women with genital HSV-2 greater
      than 2 years after acquisition.

PMID- 29175900
TI  - Former USA Gymnastics team doctor pleads guilty to sexual assault.

PMID- 29175901
TI  - Impact of weight loss on inflammation and red blood cell biomarkers after
      laparoscopic gastric banding surgery.
AB  - Adipose tissue produces several adipokines that are enrolled in different
      metabolic and inflammatory pathways that may disturb iron metabolism and
      erythropoiesis. Considering that laparoscopic adjustable gastric banding (LAGB)
      has not been associated with a long-term risk of malabsorption, we performed a 13
      month follow-up study in severe obese patients submitted to LAGB in order to
      clarify its impact on inflammation, iron metabolism and on red blood cell (RBC)
      biomarkers. Twenty obese patients were enrolled in the study, being clinical and
      analytically assessed before (T0) and 13 months after LAGB intervention (T1).
      Inflammation, iron bioavailability and RBC biomarkers were evaluated at T0 and
      T1. At T1, weight and anthropometric indices decreased significantly; patients
      showed a significant increase in mean corpuscular volume, mean corpuscular
      hemoglobin and mean corpuscular hemoglobin concentration (MCHC), and a reduction
      in red cell distribution width, ferritin, hepcidin, tumor necrosis factor-alpha,
      interleukin-6 (IL-6) and C-reactive protein. Before LAGB, IL-6 correlated
      negatively with iron, hemoglobin concentration and MCHC; hepcidin correlated
      inversely with transferrin. Our data show that 13 months after LAGB, the weight
      loss is associated with an improvement in inflammation, namely a reduction in IL
      6 that may reduce hepcidin production, improving iron availability for
      erythropoiesis, as shown by more adequate erythrocyte hemoglobinization.

PMID- 29175902
TI  - Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic,
      randomised, double blind, placebo controlled trial (Aspirin4VLU).
AB  - Objective To determine the effect of low dose aspirin on ulcer healing in
      patients with venous leg ulcers.Design Pragmatic, community based, parallel
      group, double blind, randomised controlled trial.Setting Five community nursing
      centres in New Zealand.Participants 251 adults with venous leg ulcers who could
      safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126
      to placebo.Interventions 150 mg oral aspirin daily or matching placebo for up to
      24 weeks treatment, with compression therapy as standard background
      treatment.Main outcome measures The primary outcome was time to complete healing
      of the reference ulcer (largest ulcer if more than one ulcer was present).
      Secondary outcomes included proportion of participants healed, change in ulcer
      area, change in health related quality of life, and adverse events. Analysis was
      by intention to treat.Results The median number of days to healing of the
      reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard
      ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of
      participants healed at the endpoint was 88 (70%) in the aspirin group and 101
      (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4%
      to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm2 in the aspirin group
      and 4.8 cm2 in the placebo group (mean difference -0.7 cm2, 95% confidence
      interval -1.9 to 0.5 cm2, P=0.25). 40 adverse events occurred among 29
      participants in the aspirin group and 37 adverse events among 27 participants in
      the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7,
      P=0.71).Conclusion Our findings do not support the use of low dose aspirin as
      adjuvant treatment for venous leg ulcers.Trial registration ClinicalTrials.gov
      NCT02158806.

PMID- 29175903
TI  - 'Switch' catalysis: from monomer mixtures to sequence-controlled block
      copolymers.
AB  - A 'Switch' catalysis method is reviewed whereby a single catalyst is switched
      between ring-opening polymerization and ring-opening copolymerization cycles. It
      allows the efficient synthesis of block copolymers from mixtures of lactones,
      epoxides, anhydrides and carbon dioxide. In order to use and further develop such
      'Switch' catalysis, it is important to understand how to monitor the catalysis
      and characterize the product block copolymers. Here, a step-by-step guide to both
      the catalysis and the identification of block copolymers is presented.This
      article is part of a discussion meeting issue 'Providing sustainable catalytic
      solutions for a rapidly changing world'.

PMID- 29175905
TI  - X-ray physico-chemical imaging during activation of cobalt-based Fischer-Tropsch
      synthesis catalysts.
AB  - The imaging of catalysts and other functional materials under reaction conditions
      has advanced significantly in recent years. The combination of the computed
      tomography (CT) approach with methods such as X-ray diffraction (XRD), X-ray
      fluorescence (XRF) and X-ray absorption near-edge spectroscopy (XANES) now
      enables local chemical and physical state information to be extracted from within
      the interiors of intact materials which are, by accident or design,
      inhomogeneous. In this work, we follow the phase evolution during the initial
      reduction step(s) to form Co metal, for Co-containing particles employed as
      Fischer-Tropsch synthesis (FTS) catalysts; firstly, working at small length
      scales (approx. micrometre spatial resolution), a combination of sample size and
      density allows for transmission of comparatively low energy signals enabling the
      recording of 'multimodal' tomography, i.e. simultaneous XRF-CT, XANES-CT and XRD
      CT. Subsequently, we show high-energy XRD-CT can be employed to reveal extent of
      reduction and uniformity of crystallite size on millimetre-sized TiO2 trilobes.
      In both studies, the CoO phase is seen to persist or else evolve under particular
      operating conditions and we speculate as to why this is observed.This article is
      part of a discussion meeting issue 'Providing sustainable catalytic solutions for
      a rapidly changing world'.

PMID- 29175906
TI  - Traumatic pneumocephaly: trapped air from where?
AB  - Traumatic pneumocephaly is literally defined as 'air in the head' after trauma.
      While this phenomenon has been well described in the literature, our case report
      is unique in describing diffuse pneumocephalus in the subaponeurotic space,
      subdural space, subarachnoid space, brain and ventricles without a break in the
      cranial vault: a 26-year-old man fell from a =9 meter scaffolding in a water
      tower. Following an arduous and delayed extrication, the patient was unresponsive
      with loss of pulse requiring intubation, cardiopulmonary resuscitation and
      release of tension pneumothorax with bilateral thoracostomy tubes. Examination
      remained poor with a Glasgow Coma Scale of 3. Immediate exploratory laparotomy
      was performed for a small right retroperitoneal haematoma on Focused Assessment
      with Sonography for Trauma. Postoperative imaging revealed diffuse pneumocephaly
      without facial fractures. This case presentation explores unusual causes of
      fistulous connections with the atmosphere that may lead to air trapped in and
      around the cranial vault.

PMID- 29175904
TI  - Cohesin SA2 is a sequence-independent DNA-binding protein that recognizes DNA
      replication and repair intermediates.
AB  - Proper chromosome alignment and segregation during mitosis depend on cohesion
      between sister chromatids, mediated by the cohesin protein complex, which also
      plays crucial roles in diverse genome maintenance pathways. Current models
      attribute DNA binding by cohesin to entrapment of dsDNA by the cohesin ring
      subunits (SMC1, SMC3, and RAD21 in humans). However, the biophysical properties
      and activities of the fourth core cohesin subunit SA2 (STAG2) are largely
      unknown. Here, using single-molecule atomic force and fluorescence microscopy
      imaging as well as fluorescence anisotropy measurements, we established that SA2
      binds to both dsDNA and ssDNA, albeit with a higher binding affinity for ssDNA.
      We observed that SA2 can switch between the 1D diffusing (search) mode on dsDNA
      and stable binding (recognition) mode at ssDNA gaps. Although SA2 does not
      specifically bind to centromeric or telomeric sequences, it does recognize DNA
      structures often associated with DNA replication and double-strand break repair,
      such as a double-stranded end, single-stranded overhang, flap, fork, and ssDNA
      gap. SA2 loss leads to a defect in homologous recombination-mediated DNA double
      strand break repair. These results suggest that SA2 functions at intermediate DNA
      structures during DNA transactions in genome maintenance pathways. These findings
      have important implications for understanding the function of cohesin in these
      pathways.

PMID- 29175907
TI  - What is the cause of this fever? Malaria with concomitant pneumonia.
AB  - A 43-year-old Hispanic woman presented to the clinic complaining of fever, chills
      and cough for 14 days. The patient reported a recent trip to Asia 12 days prior
      to presenting symptoms. Given her physical examination findings, she was treated
      empirically for community acquired pneumonia. Since her symptoms worsened despite
      the antibiotic, she was referred to the Emergency Department for further
      evaluation. The patient was ultimately diagnosed with pneumonia and malaria. When
      evaluating patients with history of recent travel, it is important to consider
      communicable diseases that are endemic to the areas visited, as well as multiple
      disease aetiologies for complicated and refractory cases.

PMID- 29175908
TI  - 'You can keep your hat on': a giant forehead trichilemmal cyst.

PMID- 29175909
TI  - Tension pneumothorax and pneumoperitoneum after double-lumen endotracheal
      intubation.

PMID- 29175911
TI  - The future is female.

PMID- 29175910
TI  - PAWS1 controls cytoskeletal dynamics and cell migration through association with
      the SH3 adaptor CD2AP.
AB  - Our previous studies of PAWS1 (protein associated with SMAD1; also known as
      FAM83G) have suggested that this molecule has roles beyond BMP signalling. To
      investigate these roles, we have used CRISPR/Cas9 to generate PAWS1-knockout U2OS
      osteosarcoma cells. Here, we show that PAWS1 plays a role in the regulation of
      the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell
      migration. Confocal microscopy and live cell imaging of actin in U2OS cells
      indicate that PAWS1 is also involved in cytoskeletal dynamics and organization.
      Loss of PAWS1 causes severe defects in F-actin organization and distribution as
      well as in lamellipodial organization, resulting in impaired cell migration.
      PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP
      at lamellae, suggesting that its association with CD2AP controls actin
      organization and cellular migration. Genetic ablation of CD2AP from U2OS cells
      instigates actin and cell migration defects reminiscent of those seen in PAWS1
      knockout cells.This article has an associated First Person interview with the
      first authors of the paper.

PMID- 29175912
TI  - Future health and welfare crises predicted for the brachycephalic dog population.

PMID- 29175914
TI  - Different TB pictures require different approaches to control, says Wales' CVO.

PMID- 29175916
TI  - Gaining insight into the changing needs and expectations of the vet profession.

PMID- 29175918
TI  - No deal on Brexit will increase demand for vets to deliver Irish border controls.

PMID- 29175920
TI  - Campaign to keep heavy hooves on the ground.
AB  - Declining populations of the three native breeds of heavy horse in the UK has
      prompted a charity appeal for support to preserve valuable genetic material.
      Kathryn Clark reports.

PMID- 29175925
TI  - Dismay as MPs reject Brexit Bill amendment recognising animal sentience.

PMID- 29175931
TI  - Differentiating between food bloat and gastric dilatation and volvulus in dogs.

PMID- 29175932
TI  - Is ciclosporin an effective treatment for canine pemphigus foliaceus?

PMID- 29175934
TI  - UK border control and imported dogs.

PMID- 29175935
TI  - Reptile keeping and care.

PMID- 29175936
TI  - Gudrun Ravetz, BVA Senior Vice President, responds.

PMID- 29175937
TI  - RCVS stand on homeopathy.

PMID- 29175938
TI  - Clifford Warwick, lead author of 'Future of keeping pet reptiles and amphibians:
      animal welfare and public health perspective', responds.

PMID- 29175941
TI  - The benefits of a regulatory sandbox.

PMID- 29175942
TI  - Richard Watson.
AB  - An inspirational equine veterinary surgeon with a keen interest in racing, to
      whom horses were a way of life. He took much pride in the success of his homebred
      racehorses.

PMID- 29175945
TI  - Targeting RNA G-quadruplexes as new treatment strategy for C9orf72 ALS/FTD.

PMID- 29175947
TI  - General practice warns of bankruptcy because of high service charges.

PMID- 29175946
TI  - Hypertrophied myocardium is vulnerable to ischemia/reperfusion injury and
      refractory to rapamycin-induced protection due to increased oxidative/nitrative
      stress.
AB  - Left ventricular hypertrophy (LVH) is causally related to increased morbidity and
      mortality following acute myocardial infarction (AMI) via still unknown
      mechanisms. Although rapamycin exerts cardioprotective effects against myocardial
      ischemia/reperfusion (MI/R) injury in normal animals, whether rapamycin-elicited
      cardioprotection is altered in the presence of LVH has yet to be determined.
      Pressure overload induced cardiac hypertrophied mice and sham-operated controls
      were exposed to AMI by coronary artery ligation, and treated with vehicle or
      rapamycin 10 min before reperfusion. Rapamycin produced marked cardioprotection
      in normal control mice, whereas pressure overload induced cardiac hypertrophied
      mice manifested enhanced myocardial injury, and was refractory to rapamycin
      elicited cardioprotection evidenced by augmented infarct size, aggravated
      cardiomyocyte apoptosis, and worsening cardiac function. Rapamycin alleviated
      MI/R injury via ERK-dependent antioxidative pathways in normal mice, whereas
      cardiac hypertrophied mice manifested markedly exacerbated oxidative/nitrative
      stress after MI/R evidenced by the increased iNOS/gp91phox expression, superoxide
      production, total NO metabolites, and nitrotyrosine content. Moreover, scavenging
      superoxide or peroxynitrite by selective gp91phox assembly inhibitor gp91ds-tat
      or ONOO- scavenger EUK134 markedly ameliorated MI/R injury, as shown by reduced
      myocardial oxidative/nitrative stress, alleviated myocardial infarction, hindered
      cardiomyocyte apoptosis, and improved cardiac function in aortic-banded mice.
      However, no additional cardioprotective effects were achieved when we combined
      rapamycin and gp91ds-tat or EUK134 in ischemic/reperfused hearts with or without
      LVH. These results suggest that cardiac hypertrophy attenuated rapamycin-induced
      cardioprotection by increasing oxidative/nitrative stress and scavenging
      superoxide/peroxynitrite protects the hypertrophied heart from MI/R.

PMID- 29175948
TI  - Increased nonHDL cholesterol levels cause muscle wasting and ambulatory
      dysfunction in the mouse model of LGMD2B.
AB  - Progressive limb and girdle muscle atrophy leading to loss of ambulation is a
      hallmark of dysferlinopathies, which include limb-girdle muscular dystrophy type
      2B and Miyoshi myopathy. However, animal models fail to fully reproduce the
      disease severity observed in humans, with dysferlin-null (Dysf-/-) mice
      exhibiting minor muscle damage and weakness without dramatic ambulatory
      dysfunction. As we have previously reported significant Dysf expression in blood
      vessels, we investigated the role of vascular function in development of muscle
      pathology by generating a Dysf-deficient mouse model with vascular disease. This
      was achieved by crossing Dysf-/- mice with ApoE-/- mice, which have high levels
      of nonHDL-associated cholesterol. Double-knockout Dysf-/-ApoE-/- mice exhibited
      severe ambulatory dysfunction by 11 months of age. In limb-girdle muscles,
      histology confirmed dramatic muscle wasting, fibrofatty replacement, and myofiber
      damage in Dysf-/-ApoE-/- mice without affecting the ratio of centrally nucleated
      myofibers. Although there were no major changes in ex vivo diaphragm and soleus
      muscle function, histological analyses revealed these muscles to be untouched by
      damage and remodelling. In all, these data suggest that cholesterol may be
      deleterious to dysferlinopathic muscle and lead to ambulatory dysfunction.
      Moreover, differences in plasma lipid handling between mice and humans could be a
      key factor affecting dysferlinopathy severity.

PMID- 29175950
TI  - The 2017 Budget and the NHS: experts give their verdict.

PMID- 29175949
TI  - Efficient utilization of renewable feedstocks: the role of catalysis and process
      design.
AB  - Renewable carbon feedstocks such as biomass and CO2 present an important element
      of future circular economy. Especially biomass as highly functionalized feedstock
      provides manifold opportunities for the transformation into attractive platform
      chemicals. However, this change of the resources requires a paradigm shift in
      refinery design. Fossil feedstocks are processed in gas phase at elevated
      temperature. In contrast, biorefineries are based on processes in polar solvents
      at moderate conditions to selectively deoxygenate the polar, often thermally
      instable and high-boiling molecules. Here, challenges of catalytic deoxygenation,
      novel strategies for separation and opportunities provided at the interface to
      biotechnology are discussed in form of showcases.This article is part of a
      discussion meeting issue 'Providing sustainable catalytic solutions for a rapidly
      changing world'.

PMID- 29175951
TI  - Socratic questions and frozen shoulders: teaching without telling.

PMID- 29175952
TI  - Modulation of Ether-a-Go-Go Related Gene (ERG) Current Governs Intrinsic
      Persistent Activity in Rodent Neocortical Pyramidal Cells.
AB  - While cholinergic receptor activation has long been known to dramatically enhance
      the excitability of cortical neurons, the cellular mechanisms responsible for
      this effect are not well understood. We used intracellular recordings in rat
      (both sexes) neocortical brain slices to assess the ionic mechanisms supporting
      persistent firing modes triggered by depolarizing stimuli following cholinergic
      receptor activation. We found multiple lines of evidence suggesting that a
      component of the underlying hyperexcitability associated with persistent firing
      reflects a reduction in the standing (leak) K+ current mediated by Ether-a-go-go
      Related Gene (ERG) channels. Three chemically diverse ERG channel blockers
      (terfenadine, ErgToxin-1, and E-4031) abolished persistent firing and the
      underlying increase in input resistance in deep pyramidal cells in temporal and
      prefrontal association neocortex. Calcium accumulation during triggering stimuli
      appears to attenuate ERG currents, leading to membrane potential depolarization
      and increased input resistance, two critical elements generating persistent
      firing. Our results also suggest that ERG current normally governs cortical
      neuron responses to depolarizing stimuli by opposing prolonged discharges and by
      enhancing the poststimulus repolarization. The broad expression of ERG channels
      and the ability of ERG blocks to abolish persistent firing evoked by both
      synaptic and intracellular step stimuli suggest that modulation of ERG channels
      may underlie many forms of persistent activity observed in vivoSIGNIFICANCE
      STATEMENT Persistent activity, where spiking continues beyond the triggering
      stimulus, is a common phenomenon observed in many types of neurons. Identifying
      the mechanism underlying this elementary process of memory is a step forward in
      understanding higher cognitive function including short-term memory. Our results
      suggest that a reduction in the currents normally mediated by Ether-a-go-go
      Related Gene (ERG) K+ channels contributes to persistent firing in neocortical
      pyramidal cells. ERG currents have been previously studied primarily in the
      heart; relatively little is known about ERG function in the brain, although
      mutations in ERG channels have recently been linked to schizophrenia. The present
      study is among the first to describe its role in neocortex in relation to
      biophysical correlates of memory function.

PMID- 29175953
TI  - Distinct Roles of Different Presynaptic and Postsynaptic NCAM Isoforms in Early
      Motoneuron-Myotube Interactions Required for Functional Synapse Formation.
AB  - The neural cell adhesion molecule (NCAM) is expressed both presynaptically and
      postsynaptically during neuromuscular junction formation. Genetic deletion in
      mice of all three isoforms (180, 140, and 120 kDa), or just the 180 isoform,
      suggested that different isoforms played distinct roles in synaptic maturation.
      Here we characterized in mice of either sex the earliest adhesive contacts
      between the growth cones of motoneurons and myotubes and their subsequent
      maturation into functional synapses in cocultures of motoneurons and myotubes,
      which expressed their normal complement of NCAM isoforms, or were lacking all
      isoforms either presynaptically or postsynaptically. Growth cone contact with +/+
      mouse myotubes resulted in immediate adhesive contacts and the rapid
      downregulation of growth cone motility. When contacting NCAM-/- myotubes, growth
      cones touched and retracted/collapsed multiple times and failed to form stable
      contacts, even after 10 h. Exogenous expression in myotubes of either the 180 or
      140 isoform, but not the 120 kDa isoform, rescued the rapid formation of stable
      contacts, the accumulation of presynaptic and postsynaptic molecules, and
      functional transmission. When NCAM was absent only in motoneurons, growth cones
      did not retract upon myotube contact, but, since their motility was not
      downregulated, they grew off the ends of the myotubes, failing to form synapses.
      The agrin receptor Lrp4 was strongly downregulated in NCAM-negative myotubes, and
      motoneuron growth cones did not make stable contacts with Lrp4-negative myotubes.
      These studies have identified novel roles for presynaptic and postsynaptic NCAM
      in mediating early cell-cell interactions required for synapse
      formation.SIGNIFICANCE STATEMENT Although many molecular signals needed to form
      the functionally effective neuromuscular synapses required for normal movement
      have been described, the earliest signals that let motoneuron growth cones make
      stable adhesive contacts with myotubes and cease motility are not well
      understood. Using dynamic imaging of motoneuron-myotube cocultures, we show that
      NCAM is required on both the growth cone and myotube and that different NCAM
      isoforms mediate initial adhesion and the downregulation of growth cone motility.
      The agrin receptor Lrp4 was also essential for initial adhesive contacts and was
      downregulated on NCAM-/- myotubes. Our identification of novel roles for NCAM and
      Lrp4 and possible interactions between them in transforming motile growth cones
      into stable contacts opens interesting new avenues for exploration.

PMID- 29175954
TI  - CD44 Signaling Mediates High Molecular Weight Hyaluronan-Induced
      Antihyperalgesia.
AB  - We studied, in male Sprague Dawley rats, the role of the cognate hyaluronan
      receptor, CD44 signaling in the antihyperalgesia induced by high molecular weight
      hyaluronan (HMWH). Low molecular weight hyaluronan (LMWH) acts at both
      peptidergic and nonpeptidergic nociceptors to induce mechanical hyperalgesia that
      is prevented by intrathecal oligodeoxynucleotide antisense to CD44 mRNA, which
      also prevents hyperalgesia induced by a CD44 receptor agonist, A6. Ongoing LMWH
      and A6 hyperalgesia are reversed by HMWH. HMWH also reverses the hyperalgesia
      induced by diverse pronociceptive mediators, prostaglandin E2, epinephrine,
      TNFalpha, and interleukin-6, and the neuropathic pain induced by the cancer
      chemotherapy paclitaxel. Although CD44 antisense has no effect on the
      hyperalgesia induced by inflammatory mediators or paclitaxel, it eliminates the
      antihyperalgesic effect of HMWH. HMWH also reverses the hyperalgesia induced by
      activation of intracellular second messengers, PKA and PKCepsilon, indicating
      that HMWH-induced antihyperalgesia, although dependent on CD44, is mediated by an
      intracellular signaling pathway rather than as a competitive receptor antagonist.
      Sensitization of cultured small-diameter DRG neurons by prostaglandin E2 is also
      prevented and reversed by HMWH. These results demonstrate the central role of
      CD44 signaling in HMWH-induced antihyperalgesia, and establish it as a
      therapeutic target against inflammatory and neuropathic pain.SIGNIFICANCE
      STATEMENT We demonstrate that hyaluronan (HA) with different molecular weights
      produces opposing nociceptive effects. While low molecular weight HA increases
      sensitivity to mechanical stimulation, high molecular weight HA reduces
      sensitization, attenuating inflammatory and neuropathic hyperalgesia. Both
      pronociceptive and antinociceptive effects of HA are mediated by activation of
      signaling pathways downstream CD44, the cognate HA receptor, in nociceptors.
      These results contribute to our understanding of the role of the extracellular
      matrix in pain, and indicate CD44 as a potential therapeutic target to alleviate
      inflammatory and neuropathic pain.

PMID- 29175956
TI  - The Mouse Pulvinar Nucleus Links the Lateral Extrastriate Cortex, Striatum, and
      Amygdala.
AB  - The pulvinar nucleus is a large thalamic structure involved in the integration of
      visual and motor signals. The pulvinar forms extensive connections with striate
      and extrastriate cortical areas, but the impact of these connections on cortical
      circuits has not previously been directly tested. Using a variety of anatomical,
      optogenetic, and in vitro physiological techniques in male and female mice, we
      show that pulvinocortical terminals are densely distributed in the extrastriate
      cortex where they form synaptic connections with spines and small-diameter
      dendrites. Optogenetic activation of these synapses in vitro evoked large
      excitatory postsynaptic responses in the majority of pyramidal cells, spiny
      stellate cells, and interneurons within the extrastriate cortex. However,
      specificity in pulvinar targeting was revealed when recordings were targeted to
      projection neuron subtypes. The neurons most responsive to pulvinar input were
      those that project to the striatum and amygdala (76% responsive) or V1 (55%),
      whereas neurons that project to the superior colliculus were rarely responsive
      (6%). Because the pulvinar also projects directly to the striatum and amygdala,
      these results establish the pulvinar nucleus as a hub linking the visual cortex
      with subcortical regions involved in the initiation and control of movement. We
      suggest that these circuits may be particularly important for coordinating body
      movements and visual perception.SIGNIFICANCE STATEMENT We found that the pulvinar
      nucleus can strongly influence extrastriate cortical circuits and exerts a
      particularly strong impact on the activity of extrastriate neurons that project
      to the striatum and amygdala. Our results suggest that the conventional
      hierarchical view of visual cortical processing may not apply to the mouse visual
      cortex. Instead, our results establish the pulvinar nucleus as a hub linking the
      visual cortex with subcortical regions involved in the initiation and control of
      movement, and predict that the execution of visually guided movements relies on
      this network.

PMID- 29175955
TI  - The Autism Protein Ube3A/E6AP Remodels Neuronal Dendritic Arborization via
      Caspase-Dependent Microtubule Destabilization.
AB  - UBE3A gene copy number variation and the resulting overexpression of the protein
      E6AP is directly linked to autism spectrum disorders (ASDs). However, the
      underlying cellular and molecular neurobiology remains less clear. Here we report
      the role of ASD-related increased dosage of Ube3A/E6AP in dendritic arborization
      during brain development. We show that increased E6AP expression in primary
      cultured neurons leads to a reduction in dendritic branch number and length. The
      E6AP-dependent remodeling of dendritic arborization results from retraction of
      dendrites by thinning and fragmentation at the tips of dendrite branches, leading
      to shortening or removal of dendrites. This remodeling effect is mediated by the
      ubiquitination and degradation of XIAP (X-linked inhibitors of aptosis protein)
      by E6AP, which leads to activation of caspase-3 and cleavage of microtubules. In
      vivo, male and female Ube3A 2X ASD mice show decreased XIAP levels, increased
      caspase-3 activation, and elevated levels of tubulin cleavage. Consistently,
      dendritic branching and spine density are reduced in cortical neurons of Ube3A 2X
      ASD mice. In revealing an important role for Ube3A/E6AP in ASD-related
      developmental alteration in dendritic arborization and synapse formation, our
      findings provide new insights into the pathogenesis of Ube3A/E6AP-dependent
      ASD.SIGNIFICANCE STATEMENT Copy number variation of the UBE3A gene and aberrant
      overexpression of the gene product E6AP protein is a common cause of autism
      spectrum disorders (ASDs). During brain development, dendritic growth and
      remodeling play crucial roles in neuronal connectivity and information
      integration. We found that in primary neurons and in Ube3A transgenic autism
      mouse brain, overexpression of E6AP leads to significant loss of dendritic
      arborization. This effect is mediated by the ubiquitination of XIAP (X-linked
      inhibitor of aptosis protein) by E6AP, subsequent activation of caspases, and the
      eventual cleavage of microtubules, leading to local degeneration and retraction
      at the tips of dendritic branches. These findings demonstrate dysregulation in
      neuronal structural stability as a major cellular neuropathology in ASD.

PMID- 29175957
TI  - Brainstem Pain-Control Circuitry Connectivity in Chronic Neuropathic Pain.
AB  - Preclinical investigations have suggested that altered functioning of brainstem
      pain-modulation circuits may be crucial for the maintenance of some chronic pain
      conditions. While some human psychophysical studies show that patients with
      chronic pain display altered pain-modulation efficacy, it remains unknown whether
      brainstem pain-modulation circuits are altered in individuals with chronic pain.
      The aim of the present investigation was to determine whether, in humans, chronic
      pain following nerve injury is associated with altered ongoing functioning of the
      brainstem descending modulation systems. Using resting-state functional magnetic
      resonance imaging, we found that male and female patients with chronic
      neuropathic orofacial pain show increased functional connectivity between the
      rostral ventromedial medulla (RVM) and other brainstem pain-modulatory regions,
      including the ventrolateral periaqueductal gray (vlPAG) and locus ceruleus (LC).
      We also identified an increase in RVM functional connectivity with the region
      that receives orofacial nociceptor afferents, the spinal trigeminal nucleus. In
      addition, the vlPAG and LC displayed increased functional connectivity strengths
      with higher brain regions, including the hippocampus, nucleus accumbens, and
      anterior cingulate cortex, in individuals with chronic pain. These data reveal
      that chronic pain is associated with altered ongoing functioning within the
      endogenous pain-modulation network. These changes may underlie enhanced
      descending facilitation of processing at the primary synapse, resulting in
      increased nociceptive transmission to higher brain centers. Further, our findings
      show that higher brain regions interact with the brainstem modulation system
      differently in chronic pain, possibly reflecting top-down engagement of the
      circuitry alongside altered reward processing in pain conditions.SIGNIFICANCE
      STATEMENT Experimental animal models and human psychophysical studies suggest
      that altered functioning of brainstem pain-modulation systems contributes to the
      maintenance of chronic pain. However, the function of this circuitry has not yet
      been explored in humans with chronic pain. In this study, we report that
      individuals with orofacial neuropathic pain show altered functional connectivity
      between regions within the brainstem pain-modulation network. We suggest that
      these changes reflect largely central mechanisms that feed back onto the primary
      nociceptive synapse and enhance the transfer of noxious information to higher
      brain regions, thus contributing to the constant perception of pain. Identifying
      the mechanisms responsible for the maintenance of neuropathic pain is imperative
      for the development of more efficacious therapies.

PMID- 29175958
TI  - Amphetamine Reverses Escalated Cocaine Intake via Restoration of Dopamine
      Transporter Conformation.
AB  - Cocaine abuse disrupts dopamine system function, and reduces cocaine inhibition
      of the dopamine transporter (DAT), which results in tolerance. Although tolerance
      is a hallmark of cocaine addiction and a DSM-V criterion for substance abuse
      disorders, the molecular adaptations producing tolerance are unknown, and testing
      the impact of DAT changes on drug taking behaviors has proven difficult. In
      regard to treatment, amphetamine has shown efficacy in reducing cocaine intake;
      however, the mechanisms underlying these effects have not been explored. The
      goals of this study were twofold; we sought to (1) identify the molecular
      mechanisms by which cocaine exposure produces tolerance and (2) determine whether
      amphetamine-induced reductions in cocaine intake are connected to these
      mechanisms. Using cocaine self-administration and fast-scan cyclic voltammetry in
      male rats, we show that low-dose, continuous amphetamine treatment, during self
      administration or abstinence, completely reversed cocaine tolerance. Amphetamine
      treatment also reversed escalated cocaine intake and decreased motivation to
      obtain cocaine as measured in a behavioral economics task, thereby linking
      tolerance to multiple facets of cocaine use. Finally, using fluorescence
      resonance energy transfer imaging, we found that cocaine tolerance is associated
      with the formation of DAT-DAT complexes, and that amphetamine disperses these
      complexes. In addition to extending our basic understanding of DATs and their
      role in cocaine reinforcement, we serendipitously identified a novel therapeutic
      target: DAT oligomer complexes. We show that dispersion of oligomers is
      concomitant with reduced cocaine intake, and propose that pharmacotherapeutics
      aimed at these complexes may have potential for cocaine addiction
      treatment.SIGNIFICANCE STATEMENT Tolerance to cocaine's subjective effects is a
      cardinal symptom of cocaine addiction and a DSM-V criterion for substance abuse
      disorders. However, elucidating the molecular adaptions that produce tolerance
      and determining its behavioral impact have proven difficult. Using cocaine self
      administration in rats, we link tolerance to cocaine effects at the dopamine
      transporter (DAT) with aberrant cocaine-taking behaviors. Further, tolerance was
      associated with multi-DAT complexes, which formed after cocaine exposure.
      Treatment with amphetamine deconstructed DAT complexes, reversed tolerance, and
      decreased cocaine seeking. These data describe the behavioral consequence of
      cocaine tolerance, provide a putative mechanism for its development, and suggest
      that compounds that disperse DAT complexes may be efficacious treatments for
      cocaine addiction.

PMID- 29175960
TI  - Silver-palladium catalysts for the direct synthesis of hydrogen peroxide.
AB  - A series of bimetallic silver-palladium catalysts supported on titania were
      prepared by wet impregnation and assessed for the direct synthesis of hydrogen
      peroxide, and its subsequent side reactions. The addition of silver to a
      palladium catalyst was found to significantly decrease hydrogen peroxide
      productivity and hydrogenation, but crucially increase the rate of decomposition.
      The decomposition product, which is predominantly hydroxyl radicals, can be used
      to decrease bacterial colonies. The interaction between silver and palladium was
      characterized using scanning electron microscopy, X-ray diffraction, X-ray
      photoelectron spectroscopy (XPS) and temperature programmed reduction (TPR). The
      results of the TPR and XPS indicated the formation of a silver-palladium alloy.
      The optimal 1% Ag-4% Pd/TiO2 bimetallic catalyst was able to produce
      approximately 200 ppm of H2O2 in 30 min. The findings demonstrate that AgPd/TiO2
      catalysts are active for the synthesis of hydrogen peroxide and its subsequent
      decomposition to reactive oxygen species. The catalysts are promising for use in
      wastewater treatment as they combine the disinfectant properties of silver,
      hydrogen peroxide production and subsequent decomposition.This article is part of
      a discussion meeting issue 'Providing sustainable catalytic solutions for a
      rapidly changing world'.

PMID- 29175959
TI  - Disrupted Neuroglial Metabolic Coupling after Peripheral Surgery.
AB  - Immune-related events in the periphery can remotely affect brain function,
      contributing to neurodegenerative processes and cognitive decline. In mice,
      peripheral surgery induces a systemic inflammatory response associated with
      changes in hippocampal synaptic plasticity and transient cognitive decline,
      however, the underlying mechanisms remain unknown. Here we investigated the
      effect of peripheral surgery on neuronal-glial function within hippocampal
      neuronal circuits of relevance to cognitive processing in male mice at 6, 24, and
      72 h postsurgery. At 6 h we detect the proinflammatory cytokine IL-6 in the
      hippocampus, followed up by alterations in the mRNA and protein expression of
      astrocytic and neuronal proteins necessary for optimal energy supply to the brain
      and for the reuptake and recycling of glutamate in the synapse. Similarly, at 24
      h postsurgery the mRNA expression of structural proteins (GFAP and AQP4) was
      compromised. At this time point, functional analysis in astrocytes revealed a
      decrease in resting calcium signaling. Examination of neuronal activity by whole
      cell patch-clamp shows elevated levels of glutamatergic transmission and changes
      in AMPA receptor subunit composition at 72 h postsurgery. Finally, lactate, an
      essential energy substrate produced by astrocytes and critical for memory
      formation, decreases at 6 and 72 h after surgery. Based on temporal parallels
      with our previous studies, we propose that the previously reported cognitive
      decline observed at 72 h postsurgery in mice might be the consequence of temporal
      hippocampal metabolic, structural, and functional changes in astrocytes that lead
      to a disruption of the neuroglial metabolic coupling and consequently to a
      neuronal dysfunction.SIGNIFICANCE STATEMENT A growing body of evidence suggests
      that surgical trauma launches a systemic inflammatory response that reaches the
      brain and associates with immune activation and cognitive decline. Understanding
      the mechanisms by which immune-related events in the periphery can influence
      brain processes is essential for the development of therapies to prevent or treat
      postoperative cognitive dysfunction and other forms of cognitive decline related
      to immune-to-brain communication, such as Alzheimer's and Parkinson's diseases.
      Here we describe the temporal orchestration of a series of metabolic, structural,
      and functional changes after aseptic trauma in mice related to astrocytes and
      later in neurons that emphasize the role of astrocytes as key intermediaries
      between peripheral immune events, neuronal processing, and potentially cognition.

PMID- 29175961
TI  - Commitment to patient-centred experiences at both the organisation and clinician
      level optimises empowerment of hospitalised older adults with advanced disease.

PMID- 29175962
TI  - For the times they are a-changing.

PMID- 29175963
TI  - Preoperative virtual reality experience may improve patient satisfaction and
      reduce anxiety.

PMID- 29175964
TI  - Yoga intervention may improve health-related quality of life (HRQL), fatigue,
      depression, anxiety and sleep in patients with breast cancer.

PMID- 29175965
TI  - Own mother's milk significantly decreases the risk of bronchopulmonary dysplasia.

PMID- 29175966
TI  - Non-invasive positive pressure ventilation should be considered in patients with
      COPD and persistent hypercapnia at least 2 weeks after resolution of acute
      respiratory failure.

PMID- 29175967
TI  - Dangers of neglecting non-financial conflicts of interest in health and medicine.
AB  - Non-financial interests, and the conflicts of interest that may result from them,
      are frequently overlooked in biomedicine. This is partly due to the complex and
      varied nature of these interests, and the limited evidence available regarding
      their prevalence and impact on biomedical research and clinical practice. We
      suggest that there are no meaningful conceptual distinctions, and few practical
      differences, between financial and non-financial conflicts of interest, and
      accordingly, that both require careful consideration. Further, a better
      understanding of the complexities of non-financial conflicts of interest, and
      their entanglement with financial conflicts of interest, may assist in the
      development of a more sophisticated approach to all forms of conflicts of
      interest.

PMID- 29175968
TI  - Learning health systems, clinical equipoise and the ethics of response adaptive
      randomisation.
AB  - To give substance to the rhetoric of 'learning health systems', a variety of
      novel trial designs are being explored to more seamlessly integrate research with
      medical practice, reduce study duration and reduce the number of participants
      allocated to ineffective interventions. Many of these designs rely on response
      adaptive randomisation (RAR). However, critics charge that RAR is unethical on
      the grounds that it violates the principle of equipoise. In this paper, I
      reconstruct critiques of RAR as holding that it is inconsistent with five
      important ethical principles. I then argue that these criticisms rest on a faulty
      view of equipoise encouraged by the idea that a RAR study models the beliefs of a
      single rational agent about the relative merits of the interventions being
      studied. I outline a view in which RAR models an idealised health system in which
      diverse communities of fully informed experts shrink or grow as their constituent
      members update their expert opinions in light of reliable medical evidence. I
      show how a proper understanding of clinical equipoise can reconcile this
      conception of RAR with these five ethical principles. This analysis removes an in
      principle objection to RAR and sheds important light on the relationship between
      clinical equipoise and transient diversity in the scientific community.

PMID- 29175969
TI  - Time and motion studies of National Health Service cataract theatre lists to
      determine strategies to improve efficiency.
AB  - AIM: To provide a quantitative assessment of cataract theatre lists focusing on
      productivity and staffing levels/tasks using time and motion studies. METHODS:
      National Health Service (NHS) cataract theatre lists were prospectively observed
      in five different institutions (four NHS hospitals and one private hospital).
      Individual tasks and their timings of every member of staff were recorded.
      Multiple linear regression analyses were performed to investigate possible
      associations between individual timings and tasks. RESULTS: 140 operations were
      studied over 18 theatre sessions. The median number of scheduled cataract
      operations was 7 (range: 5-14). The average duration of an operation was 10.3
      min+/-(SD 4.11 min). The average time to complete one case including patient
      turnaround was 19.97 min (SD 8.77 min). The proportion of the surgeons' time
      occupied on total duties or operating ranged from 65.2% to 76.1% and from 42.4%
      to 56.7%, respectively. The correlations of the surgical time to patient time in
      theatre was R2=0.95. A multiple linear regression model found a significant
      association (F(3,111)=32.86, P<0.001) with R2=0.47 between the duration of one
      operation and the number of allied healthcare professionals (AHPs), the number of
      AHP key tasks and the time taken to perform these key tasks by the AHPs.
      CONCLUSIONS: Significant variability in the number of cases performed and the
      efficiency of patient flow were found between different institutions. Time and
      motion studies identified requirements for high-volume models and factors
      relating to performance. Supporting the surgeon with sufficient AHPs and tasks
      performed by AHPs could improve surgical efficiency up to approximately double
      productivity over conventional theatre models.

PMID- 29175970
TI  - Macular thickness profile and diabetic retinopathy: the Singapore Epidemiology of
      Eye Diseases Study.
AB  - BACKGROUND: To evaluate retinal thickness profiles in eyes with and without
      diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD
      OCT) among individuals with diabetes. METHODS: Participants were recruited from
      the Singapore Epidemiology of Eye Diseases Study, a population-based study among
      Chinese, Malays and Indians aged 40 years or older residing in Singapore. All
      participants underwent standardised systemic and ophthalmic examinations. Average
      thickness of the macula, ganglion cell-inner plexiform layer and outer retina
      layer (from the outer plexiform layer to the retinal pigment epithelium layer)
      were measured using SD-OCT. DR status and severity were graded based on fundus
      photographs using the modified Airlie House classification system. Participants
      with macular oedema were excluded. RESULTS: 2240 eyes from 1280 participants were
      included. Of these, 1764 (78.7%) eyes had no DR, 351 (15.7%) eyes had minimal or
      mild DR and 125 (5.6%) eyes had moderate or worse DR. After adjusting for age,
      gender, ethnicity, axial length, hypertension, glycated haemoglobin, body mass
      index, total cholesterol and diabetes duration, eyes with DR had thicker macula
      (245.44 um vs 243.04 um, P=0.03) and outer retina (124.26 um vs 123.08 um,
      P=0.01) than eyes without DR. When stratified by DR severity, thicker macula
      (250.24 um vs 242.88 um, P=0.011) and outer retina (126.4 um vs 123.0 MUm,
      P=0.006) were observed in eyes with moderate or worse, but not minimal or mild
      DR, compared with eyes without DR. CONCLUSIONS: Even in the absence of macular
      oedema, eyes with DR, particularly those with more severe DR, had thicker macular
      and outer retinal layers than eyes without DR.

PMID- 29175971
TI  - The Gender Reveal: Implications of a Cultural Tradition for Pediatric Health.

PMID- 29175972
TI  - Academic Achievement and Physical Activity: A Meta-analysis.
AB  - CONTEXT: The effect of physical activity (PA) on different areas of academic
      achievement and classroom behaviors and how different characteristics of PA
      interventions could modify the effect remain unclear. OBJECTIVE: The objective
      was twofold: (1) to assess the effect of PA interventions on academic achievement
      and classroom behaviors in childhood and (2) to determine the characteristics of
      individuals and PA programs that enhance academic performance. DATA SOURCES: We
      identified studies from the database inception to October 16, 2016. STUDY
      SELECTION: We selected intervention studies aimed at examining the effect of
      exercise on academic achievement and classroom behaviors at developmental age.
      DATA EXTRACTION: Random-effects models were used to calculate pooled effect size
      for all primary outcomes (language- and mathematics-related skills, reading,
      composite score, and time in on-task behavior). Positive values represent a
      direct relationship between PA programs and academic achievement scores or on
      task behaviors. RESULTS: A total of 26 studies (10 205 children, aged from 4 to
      13) were included. Pooled effect size (95% confidence interval) estimates were as
      follows: (1) 0.16 (-0.06 to 0.37) for language-related skills; (2) 0.21 (0.09 to
      0.33) for mathematics-related skills; (3) 0.13 (0.02 to 0.24) for reading; (4)
      0.26 (0.07 to 0.45) for composite scores; and (5) 0.77 (0.22 to 1.32) for time in
      on-task behaviors. LIMITATIONS: Limitations included the variety of tools used to
      measure academic achievement and the limited number of studies that reported the
      effect of after-school PA interventions. CONCLUSIONS: PA, especially physical
      education, improves classroom behaviors and benefits several aspects of academic
      achievement, especially mathematics-related skills, reading, and composite scores
      in youth.

PMID- 29175974
TI  - Paediatric inflammatory bowel disease: improving early diagnosis.

PMID- 29175973
TI  - Accuracy of Clinician Suspicion of Lyme Disease in the Emergency Department.
AB  - BACKGROUND: To make initial management decisions, clinicians must estimate the
      probability of Lyme disease before diagnostic test results are available. Our
      objective was to examine the accuracy of clinician suspicion for Lyme disease in
      children undergoing evaluation for Lyme disease. METHODS: We assembled a
      prospective cohort of children aged 1 to 21 years who were evaluated for Lyme
      disease at 1 of the 5 participating emergency departments. Treating physicians
      were asked to estimate the probability of Lyme disease (on a 10-point scale). We
      defined a Lyme disease case as a patient with an erythema migrans lesion or
      positive 2-tiered serology results in a patient with compatible symptoms. We
      calculated the area under the curve for the receiver operating curve as a measure
      of the ability of clinician suspicion to diagnose Lyme disease. RESULTS: We
      enrolled 1021 children with a median age of 9 years (interquartile range, 5-13
      years). Of these, 238 (23%) had Lyme disease. Clinician suspicion had a minimal
      ability to discriminate between children with and without Lyme disease: area
      under the curve, 0.75 (95% confidence interval, 0.71-0.79). Of the 554 children
      who the treating clinicians thought were unlikely to have Lyme disease (score 1
      3), 65 (12%) had Lyme disease, and of the 127 children who the treating
      clinicians thought were very likely to have Lyme disease (score 8-10), 39 (31%)
      did not have Lyme disease. CONCLUSIONS: Because clinician suspicion had only
      minimal accuracy for the diagnosis of Lyme disease, laboratory confirmation is
      required to avoid both under- and overdiagnosis.

PMID- 29175975
TI  - Lamin and the heart.
AB  - Lamins A and C are intermediate filament nuclear envelope proteins encoded by the
      LMNA gene. Mutations in LMNA cause autosomal dominant severe heart disease,
      accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive
      conduction system disease, arrhythmia and systolic impairment, lamin A/C heart
      disease is more malignant than other common DCMs due to high event rates even
      when the left ventricular impairment is mild. It has several phenotypic mimics,
      but overall it is likely to be an under-recognised cause of DCM. In certain
      clinical scenarios, particularly familial DCM with early conduction disease, the
      pretest probability of finding an LMNA mutation may be quite high.Recognising
      lamin A/C heart disease is important because implantable cardioverter
      defibrillators need to be implanted early. Promising oral drug therapies are
      within reach thanks to research into the mitogen-activated protein kinase (MAPK)
      and affiliated pathways. Personalised heart failure therapy may soon become
      feasible for LMNA, alongside personalised risk stratification, as variant-related
      differences in phenotype severity and clinical course are being steadily
      elucidated.Genotyping and family screening are clinically important both to
      confirm and to exclude LMNA mutations, but it is the three-pronged integration of
      such genetic information with functional data from in vivo cardiomyocyte
      mechanics, and pathological data from microscopy of the nuclear envelope, that is
      properly reshaping our LMNA knowledge base, one variant at a time. This review
      explains the biology of lamin A/C heart disease (genetics, structure and function
      of lamins), clinical presentation (diagnostic pointers, electrocardiographic and
      imaging features), aspects of screening and management, including current
      uncertainties, and future directions.

PMID- 29175976
TI  - Heart rate at first postdischarge visit and outcomes in patients with heart
      failure.
AB  - OBJECTIVE: Heart rate control is important to prevent adverse outcomes in
      patients with heart failure (HF). However, postdischarge activity may worsen
      heart rate control, resulting in readmission. This study aimed to explore the
      implications of the heart rate differences between discharge and the first
      outpatient visit (D-O diff). METHODS: We retrospectively identified 458 patients
      (male: 46%; mean age: 72 years) discharged after HF. The heart rates at
      admission, discharge and first outpatient visit were analysed. The primary
      outcome was a composite of cardiovascular (CV) death and readmission of non-fatal
      myocardial infarction (MI), non-fatal stroke or non-fatal HF over a mean follow
      up of 16 months. RESULTS: During follow-up, the clinical outcomes were noted in
      223 patients (49%): HF, 199; stroke, 9; MI, 6; CV death, 9. The heart rate at the
      first outpatient visit (r=-0.311, P<0.001) and D-O diff (r=0.416, P<0.001) showed
      a better correlation with the time-to-clinical event than the heart rate at
      admission or discharge. The events group displayed a pronounced heart rate
      increase (13 beats/min) from discharge to the first outpatient visit compared
      with the event-free group (a decrease of 2 beats/min). A decrease less than -15
      in the D-O diff showed a 4.5-fold risk of clinical outcomes during follow-up
      (P<0.001). CONCLUSIONS: A decreased D-O diff was related to the adverse outcomes
      of HF. The failure of heart rate control within more than 15 beats/min at the
      first outpatient visit was an independent factor for CV events.

PMID- 29175977
TI  - Patients with atrial fibrillation and coronary events: are we any closer to
      coming out from the labyrinth of the various antithrombotic strategies?

PMID- 29175978
TI  - Constrictive pericarditis: diagnosis, management and clinical outcomes.
AB  - Constrictive pericarditis (CP) is a form of diastolic heart failure that arises
      because an inelastic pericardium inhibits cardiac filling. This disorder must be
      considered in the differential diagnosis for unexplained heart failure,
      particularly when the left ventricular ejection fraction is preserved. Risk
      factors for the development of CP include prior cardiac surgery and radiation
      therapy, but most cases are still deemed to be idiopathic. Making the diagnosis
      may be challenging and requires meticulous echocardiographic assessment, often
      supplemented by cross-sectional cardiac imaging and haemodynamic catheterisation.
      The key pathophysiological concepts, which serve as the basis for many of the
      diagnostic criteria, remain: (1) dissociation of intrathoracic and intracardiac
      pressures and (2) enhanced ventricular interaction. Complete surgical
      pericardiectomy is the only effective treatment for chronic CP. A subset of
      patients with subacute inflammatory CP, often identified by cardiac MRI, may
      respond to anti-inflammatory treatments.

PMID- 29175979
TI  - Takayasu arteritis: challenges in diagnosis and management.
AB  - Takayasu arteritis (TA) is a rare disease affecting chiefly young women, although
      it can affect both men and women and persons of many different ethnicities. TA
      carries a high morbidity rate, but importantly, overall mortality has declined
      over time such that the 15-year survival rate has increased from 82.9% for
      patients diagnosed between 1957 and 1975 to 96.5% for those diagnosed from 1976
      to 1990. Severity of presenting arterial complications and delay to diagnosis
      have also decreased over the past decade owing to advances in non-invasive
      diagnostic imaging and the development of medical therapies. Despite these
      advances, there still remain significant gaps in the diagnosis and management of
      these complex patients. These gaps encompass the basic, yet extremely complex,
      tasks of defining a universally accepted diagnostic criterion, accurate
      assessment of disease activity and development of clinically meaningful and
      accurate outcome measures to guide necessary clinical trials for the management
      of these complex patients.

PMID- 29175980
TI  - Glioma Survival Prediction with Combined Analysis of In Vivo 11C-MET PET
      Features, Ex Vivo Features, and Patient Features by Supervised Machine Learning.
AB  - Gliomas are the most common type of tumor in the brain. Although the definite
      diagnosis is routinely made ex vivo by histopathologic and molecular examination,
      diagnostic work-up of patients with suspected glioma is mainly done using MRI.
      Nevertheless, l-S-methyl-11C-methionine (11C-MET) PET holds great potential in
      the characterization of gliomas. The aim of this study was to establish machine
      learning-driven survival models for glioma built on in vivo 11C-MET PET
      characteristics, ex vivo characteristics, and patient characteristics. Methods:
      The study included 70 patients with a treatment-naive glioma that was 11C-MET
      positive and had histopathology-derived ex vivo feature extraction, such as World
      Health Organization 2007 tumor grade, histology, and isocitrate dehydrogenase 1
      R132H mutational status. The 11C-MET-positive primary tumors were delineated
      semiautomatically on PET images, followed by the extraction of tumor-to
      background-based general and higher-order textural features by applying 5
      different binning approaches. In vivo and ex vivo features, as well as patient
      characteristics (age, weight, height, body mass index, Karnofsky score), were
      merged to characterize the tumors. Machine-learning approaches were used to
      identify relevant in vivo, ex vivo, and patient features and their relative
      weights for predicting 36-mo survival. The resulting feature weights were used to
      establish 3 predictive models per binning configuration: one model based on a
      combination of in vivo, ex vivo, and clinical patient information (M36IEP);
      another based on in vivo and patient information only (M36IP); and a third based
      on in vivo information only (M36I). In addition, a binning-independent model
      based on ex vivo and patient information only (M36EP) was created. The
      established models were validated in a Monte Carlo cross-validation scheme.
      Results: The most prominent machine-learning-selected and -weighted features were
      patient-based and ex vivo-based, followed by in vivo-based. The highest areas
      under the curve for our models as revealed by the Monte Carlo cross-validation
      were 0.9 for M36IEP, 0.87 for M36EP, 0.77 for M36IP, and 0.72 for M36IConclusion:
      Prediction of survival in amino acid PET-positive glioma patients was highly
      accurate using computer-supported predictive models based on in vivo, ex vivo,
      and patient features.

PMID- 29175981
TI  - Validation of Noninvasive Tracer Kinetic Analysis of 18F-Florbetaben PET Using a
      Dual-Time-Window Acquisition Protocol.
AB  - Accurate amyloid PET quantification is necessary for monitoring amyloid-beta
      accumulation and response to therapy. Currently, most of the studies are analyzed
      using the static SUV ratio (SUVR) approach because of its simplicity. However,
      this approach may be influenced by changes in cerebral blood flow (CBF) or
      radiotracer clearance. Full tracer kinetic models require arterial blood sampling
      and dynamic image acquisition. The objectives of this work were, first, to
      validate a noninvasive kinetic modeling approach for 18F-florbetaben PET using an
      acquisition protocol with the best compromise between quantification accuracy and
      simplicity and, second, to assess the impact of CBF changes and radiotracer
      clearance on SUVRs and noninvasive kinetic modeling data in 18F-florbetaben PET.
      Methods: Using data from 20 subjects (10 patients with probable Alzheimer
      dementia and 10 healthy volunteers), the nondisplaceable binding potential (BPND)
      obtained from the full kinetic analysis was compared with the SUVR and with
      noninvasive tracer kinetic methods (simplified reference tissue model and
      multilinear reference tissue model 2). Various approaches using shortened or
      interrupted acquisitions were compared with the results of the full acquisition
      (0-140 min). Simulations were performed to assess the effect of CBF and
      radiotracer clearance changes on SUVRs and noninvasive kinetic modeling outputs.
      Results: An acquisition protocol using time windows of 0-30 and 120-140 min with
      appropriate interpolation of the missing time points provided the best compromise
      between patient comfort and quantification accuracy. Excellent agreement was
      found between BPND obtained using the full protocol and BPND obtained using the
      dual-window protocol (for multilinear reference tissue model 2, BPND [dual
      window] = 0.01 + 1.00.BPND [full], R2 = 0.97; for simplified reference tissue
      model, BPND [dual-window] = 0.05 + 0.92.BPND [full], R2 = 0.93). Simulations
      showed a limited impact of CBF and radiotracer clearance changes on multilinear
      reference tissue model parameters and SUVR. Conclusion: This study demonstrated
      accurate noninvasive kinetic modeling of 18F-florbetaben PET data using a dual
      window acquisition, thus providing a good compromise between quantification
      accuracy, scan duration, and patient burden. The influence of CBF and radiotracer
      clearance changes on amyloid-beta load estimates was small. For most clinical
      research applications, the SUVR approach is appropriate. However, for
      longitudinal studies in which maximum quantification accuracy is desired, this
      noninvasive dual-window acquisition with kinetic analysis is recommended.

PMID- 29175982
TI  - Responsible Radiomics Research for Faster Clinical Translation.

PMID- 29175983
TI  - Molecular Imaging of ABCB1 and ABCG2 Inhibition at the Human Blood-Brain Barrier
      Using Elacridar and 11C-Erlotinib PET.
AB  - Transporters such as ABCB1 and ABCG2 limit the exposure of several anticancer
      drugs to the brain, leading to suboptimal treatment in the central nervous
      system. The purpose of this study was to investigate the effects of the ABCB1 and
      ABCG2 inhibitor elacridar on brain uptake using 11C-erlotinib PET. Methods:
      Elacridar and cold erlotinib were administered orally to wild-type (WT) and
      Abcb1a/b;Abcg2 knockout mice. In addition, brain uptake was measured using 11C
      erlotinib imaging and ex vivo scintillation counting in knockout and WT mice. Six
      patients with advanced solid tumors underwent 11C-erlotinib PET scans before and
      after a 1,000-mg dose of elacridar. 11C-erlotinib brain uptake was quantified by
      pharmacokinetic modeling using volume of distribution (VT) as the outcome
      parameter. In addition, 15O-H2O scans to measure cerebral blood flow were
      acquired before each 11C-erlotinib scan. Results: Brain uptake of 11C-erlotinib
      was 2.6-fold higher in Abcb1a/b;Abcg2 knockout mice than in WT mice, measured as
      percentage injected dose per gram of tissue (P = 0.01). In WT mice, the addition
      of elacridar (at systemic plasma concentrations of >=200 ng/mL) resulted in an
      increased brain concentration of erlotinib, without affecting erlotinib plasma
      concentration. In patients, the VT of 11C-erlotinib did not increase after intake
      of elacridar (0.213 +/- 0.12 vs. 0.205 +/- 0.07, P = 0.91). 15O-H2O PET showed no
      significant changes in cerebral blood flow. Elacridar exposure in patients was
      401 +/- 154 ng/mL. No increase in VT with increased elacridar plasma exposure was
      found over the 271-619 ng/mL range. Conclusion: When Abcb1 and Abcg2 were
      disrupted in mice, brain uptake of 11C-erlotinib increased both at a tracer dose
      and at a pharmacologic dose. In patients, brain uptake of 11C-erlotinib was not
      higher after administration of elacridar. The more pronounced role that ABCG2
      appears to play at the human blood-brain barrier and the lower potency of
      elacridar to inhibit ABCG2 may be an explanation of these interspecies
      differences.

PMID- 29175984
TI  - Model of Intraperitoneal Targeted alpha-Particle Therapy Shows That Posttherapy
      Cold-Antibody Boost Enhances Microtumor Radiation Dose and Treatable Tumor Sizes.
AB  - Intraperitoneally administered radiolabeled monoclonal antibodies (mAbs) have
      been tested in several clinical trials, often with promising results, but have
      never proven curative. Methods: We have previously presented simulations of
      clinically relevant amounts of intraperitoneal 90Y-mAbs for treatment of minimal
      disease and shown that such treatments are unlikely to eradicate microtumors. Our
      previous model simulated the kinetics of intraperitoneally infused radiolabeled
      mAbs in humans and showed the benefit of instead using alpha-emitters such as
      211At. In the current work, we introduce penetration of mAbs into microtumors
      with radii of up to 400 MUm. Calculations were performed using dynamic simulation
      software. To determine the radiation dose distribution in nonvascularized
      microtumors of various sizes after intraperitoneal 211At-radioimmunotherapy, we
      used an in-house-developed Monte Carlo program for microdosimetry. Our aim was to
      find methods that optimize the therapy for as wide a tumor size range as
      possible. Results: Our results show that high-specific-activity radiolabeled mAbs
      that are bound to a tumor surface will penetrate slowly compared with the half
      lives of 211At and shorter-lived radionuclides. The inner-core cells of tumors
      with radii exceeding 100 MUm may therefore not be sufficiently irradiated. For
      lower specific activities, the penetration rate and dose distribution will be
      more favorable for such tumors, but the dose to smaller microtumors and single
      cells will be low. Conclusion: Our calculations show that the addition of a boost
      with unlabeled mAb 1-5 h after therapy results in sufficient absorbed doses both
      to single cells and throughout microtumors up to approximately 300 MUm in radius.
      This finding should also hold for other high-affinity mAbs and short-lived alpha
      emitters.

PMID- 29175985
TI  - Care bundles to reduce central line-associated bloodstream infections in the
      neonatal unit: a systematic review and meta-analysis.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are
      associated with increased mortality, prolonged hospitalisation and increased
      healthcare costs. Care bundles have reduced CLABSIs in adult intensive care units
      (ICUs) but replication in paediatric ICUs has had inconsistent outcomes. A
      systematic review was performed to assess the evidence for the efficacy of care
      bundles in reducing CLABSIs in the neonatal unit (NNU). METHODS: MEDLINE, CINAHL
      and EMBASE were searched from January 2010 up to January 2017. The Cochrane
      Library, Web of Science, Zetoc and Ethos were searched for additional studies.
      Randomised controlled trials (RCTs), quasi-experimental and observational studies
      were eligible. The primary outcome measure was CLABSI rates per 1000 central
      line, or patient, days. A meta-analysis was performed using random effects
      modelling. RESULTS: Twenty-four studies were eligible for inclusion: six were
      performed in Europe, 12 were in North America, two in Australia and four were in
      low/middle-income countries. Five were observational studies and 19 were before
      and after quality improvement studies. No RCTs were found. Meta-analysis revealed
      a statistically significant reduction in CLABSIs following the introduction of
      care bundles (rate ratio=0.40 (CI 0.31 to 0.51), p<0.00001), which equates to a
      60% reduction in CLABSI rate. CONCLUSION: There is a substantial body of quasi
      experimental evidence to suggest that care bundles may reduce CLABSI rates in the
      NNU, though it is not clear which bundle elements are effective in specific
      settings. Future research should focus on determining what processes promote the
      effective implementation of infection prevention recommendations, and which
      elements represent essential components of such care bundles.

PMID- 29175986
TI  - Partial oxidation of alkanes by dioxiranes formed in situ at low temperature.
AB  - Partial oxidation catalysts capable of efficiently operating at low temperatures
      may limit the over-oxidation of alkane substrates and thereby improve
      selectivity. This work focuses on examining alkane oxidation using completely
      metal-free organocatalysts, dioxiranes. The dioxiranes employed here are
      synthesized by oxidation of a ketone using a terminal oxidant, such as hydrogen
      peroxide. Our work generates the dioxirane in situ, so that the process can be
      catalytic with respect to the ketone. To date, we have demonstrated selective
      partial oxidation of adamantane using ketone catalysts resulting in yields
      upwards of 60% towards 1-adamantanol with greater than 99% selectivity.
      Furthermore, we have demonstrated that changing the electrophilic character of
      the ketone R groups to contain more electron-donating ligands facilitates the
      dioxirane ring formation and improves overall oxidation yields. Isotopic
      labelling studies using H218O2 show the preferential incorporation of an 18O
      label into the parent ketone, providing evidence for a dioxirane intermediate
      formed in situ The isotopic labelling studies, along with solvent effect studies,
      suggest the formation of peracetic acid as a reactive intermediate.This article
      is part of a discussion meeting issue 'Providing sustainable catalytic solutions
      for a rapidly changing world'.

PMID- 29175987
TI  - Providing sustainable catalytic solutions for a rapidly changing world: a summary
      and recommendations for urgent future action.
AB  - In addition to summarizing the main thrusts of each paper presented at this
      Discussion, other urgent issues involving the role (and characterization) of new
      catalysts for eliminating oxides of nitrogen, for using CO2 liberated from steel
      mills, for fuel cells and the need for rapid decarbonization of fossil fuels are
      outlined.This article is part of a discussion meeting issue 'Providing
      sustainable catalytic solutions for a rapidly changing world'.

PMID- 29175988
TI  - US neurologist escapes jail for alleged serial sexual assaults but faces more
      accusers.

PMID- 29175989
TI  - 3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)- benzoic acid: a new cause of
      sensitiser induced occupational asthma, rhinitis and urticaria.
AB  - OBJECTIVES: 3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)-benzoic acid (BCMBA) has
      not previously been identified as a respiratory sensitiser. We detected two cases
      who presented respiratory and urticaria symptoms related to BCMBA and had
      positive skin prick tests to the agent. Subsequently, we conducted outbreak
      investigations at the BCMBA-producing factory and performed clinical examinations
      to confirm occupational diseases. METHODS: The outbreak investigations included
      observations of work processes, assessment of exposure, a medical survey with a
      questionnaire and skin prick tests with 0.5% BCMBA water solution on 85 exposed
      workers and 9 unexposed workers. We used specific inhalation or nasal challenge
      and open skin application test to investigate BCMBA-related occupational asthma,
      rhinitis and contact urticaria. RESULTS: We identified nine workers with
      respiratory and/or skin symptoms and positive skin prick tests to BCMBA in a
      chemical factory. A survey among chemical factory workers indicated a BCMBA
      related sensitisation rate of 8% among all exposed workers; the rate was highest
      (25%) among production workers in the production hall. Sensitisation was detected
      only in workers with the estimated highest exposure levels. Six cases of
      occupational asthma, rhinitis and/or contact urticaria caused by BCMBA were
      confirmed with challenge tests. Asthma-provoking doses in specific inhalation
      challenges were very low (0.03% or 0.3% BCMBA in lactose). CONCLUSIONS: We
      identified a new low molecular weight agent causing occupational asthma, rhinitis
      and contact urticaria. A typical clinical picture of allergic diseases and
      positive skin prick tests suggest underlying IgE-mediated disease mechanisms.
      Stringent exposure control measures are needed in order to prevent BCMBA-related
      diseases.

PMID- 29175990
TI  - Prevalence of occupational exposure to asthmagens derived from animals, fish
      and/or shellfish among Australian workers.
AB  - OBJECTIVE: Several animal, fish and/or shellfish derived substances encountered
      in the workplace can initiate or exacerbate asthma. The aims of this study were:
      to produce a population-based estimate of the current prevalence of occupational
      exposure to animal, fish and/or shellfish derived asthmagens, to identify the
      main circumstances of exposures and to identify occupations with the highest
      proportions of exposed respondents. METHODS: We used data from the Australian
      Work Exposure Study-Asthma, a national telephone survey that investigated the
      current prevalence of occupational exposure to asthmagens among Australian
      workers. A web-based tool was used to collect job task information and assign
      exposure to asthmagens, including animal, fish and/or shellfish derived
      asthmagens. Prevalence ratios to determine risk factors for exposure were
      estimated using modified Poisson regression. RESULTS: Of the 4878 respondents,
      12.4% were exposed to asthmagens derived from animals, fish and/or shellfish.
      Exposure to these asthmagens was significantly higher in workers residing in
      regional and remote areas, compared with major cities. The main circumstance of
      exposure to animal derived asthmagens was through cleaning up rat/mice
      infestations, while the main circumstance of exposure to fish and/or shellfish
      derived asthmagens was through preparing and cooking salmon. Occupational groups
      with the highest proportion of exposure to animal or fish and/or shellfish
      derived asthmagens were farmers/animal workers and food workers, respectively.
      CONCLUSIONS: This is the first study investigating occupational exposure to
      animal, fish and/or shellfish derived asthmagens in a nationwide working
      population. The results of this study can be used to inform the direction of
      occupational interventions and policies to reduce work-related asthma.

PMID- 29175991
TI  - Nurse education in sexual health.

PMID- 29175992
TI  - Are patients aged over 50 years being let down by sexual health clinics? Audit of
      sexual history taking in patients aged over 50 years in an integrated sexual
      health clinic in North West England.

PMID- 29175993
TI  - Eligibility for PrEP among MSM attending GUM clinics in the UK.

PMID- 29175994
TI  - Improving early HIV diagnosis, treatment and care in Europe with healthcare
      provider specific HIV indicator condition list and audits.

PMID- 29175995
TI  - Cervical lymphadenopathy due to lymphogranuloma venereum infection.

PMID- 29175996
TI  - 1917: responding to the challenge posed by venereal disease.

PMID- 29175999
TI  - Modern fertility awareness methods: wrist wearables capture the changes in
      temperature associated with the menstrual cycle.
AB  - Core and peripheral body temperatures are affected by changes in reproductive
      hormones during the menstrual cycle. Women worldwide use the basal body
      temperature (BBT) method to aid and prevent conception. However, prior research
      suggests that taking one's daily temperature can prove inconvenient and subject
      to environmental factors. We investigate whether a more automatic, non-invasive
      temperature measurement system can detect changes in temperature across the
      menstrual cycle. We examined how wrist skin temperature (WST), measured with
      wearable sensors, correlates with urinary tests of ovulation and may serve as a
      new method of fertility tracking. One hundred and thirty-six eumenorrheic, non
      pregnant women participated in an observational study. Participants wore WST
      biosensors during sleep and reported their daily activities. An at-home
      luteinizing hormone (LH) test was used to confirm ovulation. WST was recorded
      across 437 cycles (mean cycles/participant = 3.21, S.D. = 2.25). We tested the
      relationship between the fertile window and WST temperature shifts, using the BBT
      three-over-six rule. A sustained 3-day temperature shift was observed in 357/437
      cycles (82%), with the lowest cycle temperature occurring in the fertile window
      41% of the time. Most temporal shifts (307/357, 86%) occurred on ovulation day
      (OV) or later. The average early-luteal phase temperature was 0.33 degrees C
      higher than in the fertile window. Menstrual cycle changes in WST were impervious
      to lifestyle factors, like having sex, alcohol, or eating prior to bed, that, in
      prior work, have been shown to obfuscate BBT readings. Although currently
      costlier than BBT, the present study suggests that WST could be a promising,
      convenient parameter for future multiparameter fertility awareness methods.

PMID- 29175997
TI  - Up-regulated miR-500a enhances hepatocarcinoma metastasis by repressing PTEN
      expression.
AB  - It has been shown that miR-500a may play an important role in the metastasis of
      hepatocarcinoma. The present study is to explore the influence of miR-500a on
      hepatocarcinoma proliferation and metastasis, and the related molecular
      mechanism. The levels of miR-500a in the serum and tissues of patients with
      metastatic or non-metastatic hepatocarcinoma or normal people were determined by
      quantitative reverse transcription-PCR (qRT-PCR). The proliferation, invasion,
      and cloning of hepatocarcinoma cell lines SMMC-7721 after transfection with mimic
      miR-500a or inhibitor miR-500a were determined. Luciferase reported assay was
      used to explore the relationship between miR-500a and phosphatase and tensin
      homologue (PTEN). Then, the protein expression of PTEN, p-Akt (S473), p-Akt
      (T308), Akt, p-mTOR, mTOR, p-4E-BP1, 4E-BP1, p-S6K, and S6K in SMMC-7721 cells
      were also determined by Western blotting. The expression of miR-500a in patients
      with metastatic hepatocarcinoma was significantly higher than the non-metastatic
      hepatocarcinoma. Overexpression of miR-500a promoted the proliferation, invasion,
      and cloning of SMMC-7721 cells. Luciferase reported assay showed miR-500a could
      directly target at 3'-UTR of PTEN. Overexpression of miR-500a significantly
      reduced the expression of PTEN, and enhanced phosphorylation of Akt, mTOR, S6K,
      and 4E-BP1. In conclusion, the expression of miR-500a was related to the
      proliferation and metastasis of hepatocarcinoma, which may be partly because of
      the activation of AKT/mTOR pathway through targetting PTEN.

PMID- 29175998
TI  - Structural determinants for protein unfolding and translocation by the Hsp104
      protein disaggregase.
AB  - The ring-forming Hsp104 ATPase cooperates with Hsp70 and Hsp40 molecular
      chaperones to rescue stress-damaged proteins from both amorphous and amyloid
      forming aggregates. The ability to do so relies upon pore loops present in the
      first ATP-binding domain (AAA-1; loop-1 and loop-2 ) and in the second ATP
      binding domain (AAA-2; loop-3) of Hsp104, which face the protein translocating
      channel and couple ATP-driven changes in pore loop conformation to substrate
      translocation. A hallmark of loop-1 and loop-3 is an invariable and mutational
      sensitive aromatic amino acid (Tyr257 and Tyr662) involved in substrate binding.
      However, the role of conserved aliphatic residues (Lys256, Lys258, and Val663)
      flanking the pore loop tyrosines, and the function of loop-2 in protein
      disaggregation has not been investigated. Here we present the crystal structure
      of an N-terminal fragment of Saccharomyces cerevisiae Hsp104 exhibiting molecular
      interactions involving both AAA-1 pore loops, which resemble contacts with bound
      substrate. Corroborated by biochemical experiments and functional studies in
      yeast, we show that aliphatic residues flanking Tyr257 and Tyr662 are equally
      important for substrate interaction, and abolish Hsp104 function when mutated to
      glycine. Unexpectedly, we find that loop-2 is sensitive to aspartate
      substitutions that impair Hsp104 function and abolish protein disaggregation when
      loop-2 is replaced by four aspartate residues. Our observations suggest that
      Hsp104 pore loops have non-overlapping functions in protein disaggregation and
      together coordinate substrate binding, unfolding, and translocation through the
      Hsp104 hexamer.

PMID- 29176001
TI  - Dispatches from the Editor: Is the end of the print military medical journal
      inevitable?

PMID- 29176000
TI  - Effects of GABAB receptor activation on spatial cognitive function and
      hippocampal neurones in rat models of type 2 diabetes mellitus.
AB  - The present study was conducted with the aim being to investigate the effect
      gamma-aminobutyric acid type B (GABAB) receptor activation have on spatial
      cognitive function and hippocampal neurones found in the rat models of type 2
      diabetes mellitus (T2DM). T2DM rat models were then established, randomized, and
      subsequently assigned into normal control (NC), T2DM, T2DM + chemical grade
      propylene (CGP), T2DM + baclofen, and T2DM + CGP + baclofen groups. T2DM rats'
      weight and blood sugar concentrations were monitored. The DMS-2 Morris water maze
      testing system was performed in order to figure out the spatial cognitive
      function of these rats. Reverse-transcription quantitative PCR (RT-qPCR) and
      Western blotting were also performed in order to detect GABAB mRNA and protein
      expressions. We used the Nissl staining method in order to detect the number of
      hippocampal neurones, TUNEL (terminal deoxyribonucleotidy transferase-mediated
      dUTP nick labeling) staining to detect cell apoptosis, and Western blotting
      method in order to measure the expressions of the apoptosis-related proteins
      (Bax, cytochrome c (Cyt-c), Caspase-3, and Bcl-2). In comparison with the T2DM
      group, the weight decreased, blood sugar concentration increased, and spatial
      cognitive function as well as hippocampal neurones were both impaired in the T2DM
      + CGP group, contrary to the rats in the T2DM + baclofen group who showed an
      opposite trend. The situation in the T2DM + CGP + baclofen group was better than
      that found in the T2DM + CGP group while proving to be more serious than that of
      the NC and T2DM + baclofen groups. Conclusively, activating the GABAB receptor
      improved spatial cognitive function and hippocampal neurones in the T2DM rats.

PMID- 29176002
TI  - Physiological monitoring for healthy military personnel.
AB  - Military employment commonly exposes personnel to strenuous physical exertion.
      The resulting interaction between occupational stress and individual
      susceptibility to illness demands careful management. This could extend to
      prospective identification of high physiological strain in healthy personnel, in
      addition to recognition and protection of vulnerable individuals. The emergence
      and ubiquitous uptake of 'wearable' physiological and medical monitoring devices
      might help to address this challenge, but requires that the right questions are
      asked in sourcing, developing, validating and applying such technologies. Issues
      that must be addressed include system requirements, such as the likelihood of end
      users deploying and using technology as intended; interpretation of data in
      relation to pretest probability, including the potential for false-positive
      results; differentiation of pathological states from normal physiology;
      responsibility for and consequences of acting on abnormal or unexpected results
      and cost-effectiveness. Ultimately, the performance of a single monitoring
      system, in isolation or alongside other measures, should be judged by whether any
      improvement is offered versus existing capabilities and at what cost to mission
      effectiveness.

PMID- 29176003
TI  - Predicting how health behaviours contribute to the development of diseases within
      a military population in the Hungarian Defence Forces.
AB  - INTRODUCTION: Recent legislative amendments in Hungary have resulted in the
      possibility for early retirement being abolished in the Hungarian Defence Forces.
      The retirement age for professional soldiers has also increased to 65 years,
      thereby greatly increasing the average length of military service. This
      necessitates greater attention to the health and care of service personnel due to
      the increase of chronic non-communicable diseases with age. The aim of this
      research was to identify how health behaviours might potentially contribute to
      diseases in the Hungarian Defence Forces. METHODS: All members of the Hungarian
      Defence Forces undergoing health screenings between 2011 and 2015 were assessed.
      Health variables analysed were derived from the health screening data sheet which
      is collected from every member of the Hungarian Defence Forces undergoing a
      health screening since 2009. Items recorded were connected to health behaviour
      (physical activity, nutrition, smoking), subjective well-being (psychosomatic
      backache, fatigue and quality of waking up to describe the quality of sleep),
      sociodemographic data (age, gender) and the mental toughness quotient (MTQ). A
      logistic regression model was utilised to predict how health behaviour may affect
      the development of disease. RESULTS: Factors most associated with the development
      of disease included psychosomatic backache (P<0.000), age (P<0.001), frequency of
      undertaking sports (P<0.05), quality of sleeping and waking up (P<0.05) and the
      assessment of gender differences (P<0.05). CONCLUSIONS: Extension of the length
      of active service will result in an increased burden of disease for members of
      the Hungarian Defence Forces. This includes both physical and psychological
      morbidity that could potentially be obstacles for service personnel to perform
      their military duties. Health behaviours such as psychosomatic backache, the
      frequency of performing sports and sleep quality may predict the development of
      disease and should be explored in health screening consultations.

PMID- 29176004
TI  - Musculoskeletal injuries in British Army recruits: a prospective study of
      incidence in different Infantry Regiments.
AB  - BACKGROUND: Musculoskeletal injuries and attrition incurred during basic military
      training are a significant socioeconomic burden across many Defence Forces. In
      order to plan an injury prevention strategy, the purpose of this study was to
      quantify the regiment-specific musculoskeletal injury patterns and training
      outcomes. METHODS: This was a prospective observational study of the Parachute
      (n=734), Guards (n=1044), Line (n=3472) and Gurkha (n=458) Regiments of the
      British Army recruits during a 26-week basic military training programme over a 2
      year period. The participant demographic characteristics were: age 18.9 years
      (SD+/-2.3), height 176.5 cm (SD+/-7.80), mass 69 kg (SD+/-9.7) and body mass
      index 22.14 kg/m2 (SD+/-2.5). RESULTS: The incidence of injuries (86%, 46%, 48%
      and 10%) was significantly different (p<0.001) as were the first time pass out
      rates (p=0.02) of 38%, 51%, 56% and 98% for Parachute, Guards, Line and Gurkha,
      respectively. Overuse injuries were more frequently reported than both acute and
      recurrent injuries in all regiments (X2=688.01, p<0.01). CONCLUSIONS: The
      disparity in injury incidence and training outcome between Infantry Regiments
      suggests that the demands of training be taken into account when devising injury
      prevention strategies.

PMID- 29176005
TI  - Could routine spirometry suggest sensitisation in the military medicine setting?
AB  - INTRODUCTION: Providing evidence of sensitisation is the formal requirement for
      allergy diagnosis. The aim of this study was to evaluate whether spirometry may
      be able to predict sensitisation in a representative cohort of Italian Navy
      military personnel. METHODS: 2043 (1875 men, 168 women, mean age 28.35+/-11.6
      years) Italian Navy military personnel were enrolled into this study. Spirometry
      and skin prick testing were performed to predict sensitisation. RESULTS:
      Sensitisation, assessed by skin prick test, was documented in 658 (32.2%)
      subjects. Impaired forced expiratory flow at the 25% and 75% of the pulmonary
      volume (FEF25-75) as demonstrated on spirometry was detected in 82 subjects, of
      whom 69 were sensitised (P<0.0001). Impaired FEF25-75 was significantly
      associated with sensitisation (OR 7.43; 95% CI 4.04 to 14.66; P<0.0001).
      DISCUSSION: The findings of this study suggest that impaired FEF25-75 may predict
      sensitisation in this cohort of Italian Navy personnel. This outcome is relevant
      in the military medical setting, as it could allow early identification of
      subjects with subclinical asthma.

PMID- 29176006
TI  - GPR120: Mechanism of action, role and potential for medical applications.
AB  - G protein-coupled receptors (GPCRs) constitute a family of transmembrane proteins
      that mediate many cellular processes. GPR120/FFAR4, a receptor from this family
      that is activated by fatty acids, has received considerable attention recently.
      This paper presents a literature review concerning the role of GPR120 and its
      mechanism of action in animal and human studies as well as the potential use of
      GPR120 for the treatment of chronic diseases. Two electronic databases - Medline
      and Google Scholar - were searched for available studies addressing the review
      topic that were written in English and published from 2000 to June 2017. The
      following key terms were used in the search: GPR120, FFA4, GPR120 agonist, PUFAs,
      EPA, DHA, adipocyte, obesity, hyperlipidemia, inflammation, cancer, diabetes,
      insulin resistance, taste, atherogenesis, hepatis, central nervous system. In
      humans, GPR120 expression is expressed in macrophages, eosinophils, and adipose
      tissue, in cells of the tongue, liver, lungs, small and large intestine, gastric
      mucosa, and pancreas, in the central nervous system and placental microvilli.
      Medium- and long-chain fatty acids act as ligands for the receptor. Through the
      internalization of beta-arrestin-2 complex and the inhibition of NF-kappaB,
      GPR120 mediates the activation of the cell's anti-inflammatory mechanisms. The
      receptor is also involved in the maturation of adipocytes, the modulation of
      insulin signalling pathways, the regulation of glucose metabolism, and the
      secretion of intestinal hormones. GPR120 is a promising target for the treatment
      of numerous diseases, whose pathophysiology is associated with low-grade
      inflammation. As a result of intensive searches, a likely group of synthetic
      agonists of the receptor was determined with potential therapeutic applications
      in conditions such as obesity, impaired carbohydrate metabolism, inflammatory
      bowel diseases, cancer, mental disorders.

PMID- 29176007
TI  - Between biology and medicine: perspectives on the use of dendritic cells in
      anticancer therapy.
AB  - Dendritic cells (DCs), as a link between innate and adaptive immunity, play a
      pivotal role in maintaining homeostasis of the immune system. The DC population
      is characterized by heterogeneity; it consists of many subpopulations which,
      despite their phenotypic and localization differences, play an essential function
      - they are professional antigen presenting cells. Due to their role, DCs can be
      utilized in a new cancer treatment strategy. Their main purpose is to generate an
      anticancer response leading to the elimination of cancer cells. The tumor
      microenvironment, abundant in immunosuppressive factors (e.g. IL-10, TGF-beta,
      Arg1, IDO), impairs the proper function of DCs. For this reason, various
      strategies are necessary for ex vivo preparation of DC-based vaccines and for the
      support of in vivo DCs to fight against tumors. DC-based vaccines are combined
      with other forms of immunotherapy (e.g. blockade of immune checkpoint molecules,
      e.g. PD-1 or CTLA-4) or conventional types of therapies (e.g. chemotherapy).
      Despite the enormous progress that has been made in anticancer therapy in the
      past two decades, there are still many unresolved issues regarding the
      effectiveness of the DCs usage. In this paper we described, in both a mouse and a
      human subject, a series of DC subpopulations, differentiating in normal
      conditions or under the influence of cancer microenvironment. We listed factors
      affecting the quality of the in vivo and ex vivo generations of antitumoral
      responses, significant from a therapeutic point of view. Moreover, the most
      important strategies for the use of DCs in anticancer therapies, as well as
      further developments on this field, have been discussed.

PMID- 29176008
TI  - Viability and growth promotion of starter and probiotic bacteria in yogurt
      supplemented with whey protein hydrolysate during refrigerated storage.
AB  - The effect of whey protein hydrolysate (WPH) addition on growth of standard
      yoghurt cultures and Bifidobacterium adolescentis during co-fermentation and its
      viability during storage at 4oC in yoghurts has been evaluated. WPH was obtained
      with the use of serine protease from Y. lipolytica yeast. Stirred probiotic
      yoghurts were prepared by using whole milk standardized to 16% of dry matter with
      the addition of either whey protein concentrate, skim milk powder (SMP), WPH-SMP
      (ratio 1:1), WPH. The hydrolysate increased the yoghurt culture counts at the
      initial stage of fermentation and significantly inhibited the decrease in
      population viability throughout the storage at 4oC in comparison to the control.
      The post-fermentation acidification was also retarded by the addition of WPH. The
      hydrolysate did not increase the Bifidobacterium adolescentis counts at the
      initial stage. However, the WPH significantly improved its viability. After 21
      days of storage, in the yogurts supplemented with WPH, the population of these
      bacteria oscillated around 3.04 log10 CFU/g, while in samples where SMP or whey
      protein concentrate was used, the bacteria were no longer detected.

PMID- 29176009
TI  - Evaluation of long-term stability of cannabinoids in standardized preparations of
      cannabis flowering tops and cannabis oil by ultra-high-performance liquid
      chromatography tandem mass spectrometry.

PMID- 29176010
TI  - Three-year customer satisfaction survey in laboratory medicine in a Chinese
      university hospital.
AB  - BACKGROUND: Customer satisfaction is a key quality indicator of laboratory
      service. Patients and physicians are the ultimate customers in medical
      laboratory, and their opinions are essential components in developing a customer
      oriented laboratory. METHODS: A longitudinal investigation of customer
      satisfaction was conducted through questionnaires. We designed two different
      questionnaires and selected 1200 customers (600 outpatients and 600 physicians)
      to assess customer satisfaction every other year from 2012 to 2016. Items with
      scores <4 were considered unsatisfactory, and corrective actions should be taken.
      RESULTS: The completion rates of physicians were 96.8% in 2012, 97% in 2014 and
      96.5% in 2016, whereas the rates of patients were 95.3%, 96.2% and 95.2%,
      respectively. In 2012, the most dissatisfaction items were test turnaround time
      (3.77 points) and service attitude (3.87 points) from physicians, whereas waiting
      time (3.58 points) and examination environment (3.64 points) were the most
      dissatisfaction items from patients. After corrective actions were taken, the
      result of satisfaction in 2014 was better, which illustrated our strategy was
      effective. However, some items remained to be less than 4, so we repeated the
      survey after modifying questionnaires in 2016. However, the general satisfaction
      points of the physicians and patients reduced in 2016, which reminded us of some
      influential factors we had neglected. CONCLUSIONS: By using dynamic survey of
      satisfaction, we can continuously find deficiencies in our laboratory services
      and take suitable corrective actions, thereby improving our service quality.

PMID- 29176011
TI  - Estimation of fractions metabolized by hepatic CYP enzymes using a concept of
      inter-system extrapolation factors (ISEFs) - a comparison with the chemical
      inhibition method.
AB  - BACKGROUND: For estimation of fractions metabolized (fm) by different hepatic
      recombinant human CYP enzymes (rhCYP), calculation of inter-system extrapolation
      factors (ISEFs) has been proposed. METHODS: ISEF values for CYP1A2, CYP2C19 and
      CYP3A4/5 were measured. A CYP2C9 ISEF was taken from a previous report. Using a
      set of compounds, fractions metabolized by CYP enzymes (fm,CYP) values calculated
      with the ISEFs based on rhCYP data were compared with those from the chemical
      inhibition data. Oral pharmacokinetics (PK) profiles of midazolam were simulated
      using the physiologically based pharmacokinetics (PBPK) model with the CYP3A
      ISEF. For other CYPs, the in vitro fm,CYP values were compared with the reference
      fm,CYP data back-calculated with, e.g. modeling of test substrates by feeding
      clinical PK data. RESULTS: In vitro-in vitro fm,CYP3A4 relationship between the
      results from rhCYP incubation and chemical inhibition was drawn as an exponential
      correlation with R2=0.974. A midazolam PBPK model with the CYP3A4/5 ISEFs
      simulated the PK profiles within twofold error compared to the clinical
      observations. In a limited number of cases, the in vitro methods could not show
      good performance in predicting fm,CYP1A2, fm,CYP2C9 and fm,CYP2C19 values as
      reference data. CONCLUSIONS: The rhCYP data with the measured ISEFs provided
      reasonable calculation of fm,CYP3A4 values, showing slight over-estimation
      compared to chemical inhibition.

PMID- 29176012
TI  - Sirolimus therapy for congenital hyperinsulinism in an infant with a novel
      homozygous KCNJ11 mutation.
AB  - BACKGROUND: Congenital hyperinsulinism results in refractory hypoglycemia. If a
      therapy with diazoxide has been unresponsive this has been treated by subtotal
      pancreatectomy in the past. This therapeutic option poses an increased risk of
      developing diabetes at a later stage. There have been a few case reports on the
      use of sirolimus in such situations in the recent past. CASE PRESENTATION: Our
      patient was started on sirolimus very early, on day 29 of life and at the age of
      14 months is doing well on sirolimus therapy. His growth and development have
      been good and he has not had any major complications so far. Genetic testing
      showed a novel KCNJ11 homozygous mutation on next generation sequencing and the
      parents were heterozygous carriers. CONCLUSIONS: We report the successful use of
      sirolimus in the management of diazoxide unresponsive congenital hyperinsulinism
      with diffuse pancreatic involvement. We believe this is the youngest patient to
      be initiated on sirolimus so far.

PMID- 29176013
TI  - Transfusion-associated necrotizing enterocolitis in preterm infants: an updated
      meta-analysis of observational data.
AB  - BACKGROUND: The number of observational studies that report an association
      between packed red blood cell (PRBC) transfusions and necrotizing enterocolitis
      (NEC) has increased. The primary objective of this study was to evaluate the
      association between PRBC transfusions and NEC in observational studies. METHODS:
      Medline, Embase and Cochrane Library databases as well as the Pediatrics Academic
      Societies abstract archives were systematically searched to identify
      observational studies that investigated the association between PRBC transfusions
      and NEC. Key search terms included premature infant, blood transfusion and
      necrotizing enterocolitis. The generic inverse variance method with a random
      effects model was used to meta-analyze selected studies. Odds ratios (ORs) and
      confidence intervals (CIs) were calculated. RESULTS: A meta-analysis of 17
      observational studies that reported the association between PRBC transfusions and
      NEC was performed. The meta-analysis revealed no evidence of an association
      between PRBC transfusions and a higher risk of NEC (OR: 0.96; 95% CI: 0.53-1.71;
      P=0.88). The effect estimates that suggested an association between PRBC
      transfusion and NEC in matched case-control studies (OR: 1.20; 95% CI: 0.58-2.47;
      P=0.63) differed from those reported in cohort studies (OR: 0.51; 95% CI: 0.34
      0.75; P=<0.01). CONCLUSIONS: This updated meta-analysis of predominantly low-to
      moderate quality observational studies suggests that there is no significant
      association between PRBC transfusions and NEC. A higher quality of evidence on
      this topic is needed.

PMID- 29176014
TI  - Cervical pessary combined with vaginal progesterone for the prevention of
      spontaneous preterm birth: is the evidence sufficient?

PMID- 29176015
TI  - Determination of age- and sex-specific 99th percentiles for high-sensitive
      troponin T from patients: an analytical imprecision- and partitioning-based
      approach.
AB  - BACKGROUND: Detection of acute myocardial infarction (AMI) is mainly based on a
      rise of cardiac troponin with at least one value above the 99th percentile upper
      reference limit (99th URL). However, circulating high-sensitive cardiac troponin
      T (hs-cTnT) concentrations depend on age, sex and renal function. Using an
      analytical imprecision-based approach, we aimed to determine age- and sex
      specific hs-cTnT 99th URLs for patients without chronic kidney disease (CKD).
      METHODS: A 3.8-year retrospective analysis of a hospital laboratory database
      allowed the selection of adult patients with concomitant plasma hs-cTnT (<300
      ng/L) and creatinine concentrations, both assayed twice within 72 h with at least
      3 h between measurements. Absence of AMI was assumed when the variation between
      serial hs-cTnT values was below the adjusted-analytical change limit calculated
      according to the inverse polynomial regression of analytical imprecision.
      Specific URLs were determined using Clinical and Laboratory Standards Institute
      (CLSI) methods, and partitioning was tested using the proportion method, after
      adjustment for unequal prevalences. RESULTS: After outlier removal (men: 8.7%;
      women: 6.6%), 1414 men and 1082 women with estimated glomerular filtration rate
      (eGFR) >=60 mL/min/1.73 m2 were assumed as non-AMI. Partitioning into age groups
      of 18-50, 51-70 and 71-98 years, the hs-cTnT 99th URLs adjusted on French
      prevalence were 18, 33, 66 and 16, 30, 84 ng/L for men and women, respectively.
      Age-partitioning was clearly required. However, sex-partitioning was not
      justified for subjects aged 18-50 and 51-70 years for whom a common hs-cTnT 99th
      URLs of about 17 and 31 ng/L could be used. CONCLUSIONS: Based on a laboratory
      approach, this study supports the need for age-specific hs-cTnT 99th URLs.

PMID- 29176017
TI  - EASI - European Autoimmunity Standardisation Initiative: facing the challenges of
      diagnostics in autoimmunity.

PMID- 29176016
TI  - Proficiency testing program for hemoglobin E, A2 and F analysis in Thailand using
      lyophilized hemoglobin control materials.
AB  - BACKGROUND: There is no external quality assessment (EQA) program for hemoglobin
      analysis that uses lyophilized hemoglobin control materials with HbA2/E in levels
      as high as those found in people with the beta-thalassemia trait, HbE trait, beta
      thalassemia/HbE disease or homozygous HbE; these are all found frequently in the
      southeast Asian population. The aim of this study was to evaluate the efficiency
      of the control materials used in the established proficiency testing (PT) program
      at the Associated Medical Sciences-Clinical Service Center (AMC-CSC), Chiang Mai
      University, Chiang Mai, Thailand. METHODS: The PT program for Hb analysis and the
      thalassemia interpretation was established in compliance with ISO/IEC17043:2010.
      Three cycles per year were performed in 2015 and 2016. In each cycle, three
      different types of control material were provided to the participants. Each
      participant analyzed the control materials in the same manner as in their routine
      practices. Hb analysis results and their thalassemia interpretation codes were
      entered into the report form and sent back to AMC-CSC. RESULTS: The number of
      participants increased from 63 in 2015 to 76 in 2016. In addition, the number of
      participants who took part in all three cycles increased from 95.2% (60/63) in
      2015 to 100% (76/76) in 2016. All participants reported the correct Hb
      measurement and type; however, misinterpretations in thalassemia diagnosis were
      noted. CONCLUSIONS: The lyophilized hemoglobin control materials prepared at AMC
      CSC were used successfully in our PT program. However, the study results indicate
      the need for further improvement in thalassemia interpretation skills for
      laboratory staff.

PMID- 29176018
TI  - Diagnostic and prognostic value of presepsin vs. established biomarkers in
      critically ill patients with sepsis or systemic inflammatory response syndrome.
AB  - BACKGROUND: Inflammatory biomarkers may aid to distinguish between systemic
      inflammatory response syndrome (SIRS) vs. sepsis. We tested the hypotheses that
      (1) presepsin, a novel biomarker, can distinguish between SIRS and sepsis, and
      (2) higher presepsin levels will be associated with increased severity of illness
      and (3) with 28-day mortality, outperforming traditional biomarkers. METHODS:
      Procalcitonin (PCT), C-reactive protein (CRP), presepsin, and lactate were
      analyzed in 60 consecutive patients (sepsis and SIRS, n=30 per group) on day 1
      (D1) to D3 (onset sepsis, or after cardiac surgery). The systemic organ failure
      assessment (SOFA) score was determined daily. RESULTS: There was no difference in
      mortality in sepsis vs. SIRS (12/30 vs. 8/30). Patients with sepsis had higher
      SOFA score vs. patients with SIRS (11+/-4 vs. 8+/-5; p=0.023), higher presepsin
      (AUC=0.674; p<0.021), PCT (AUC=0.791; p<0.001), CRP (AUC=0.903; p<0.0001), but
      not lactate (AUC=0.506; p=0.941). Unlike other biomarkers, presepsin did not
      correlate with SOFA on D1. All biomarkers were associated with mortality on D1:
      presepsin (AUC=0.734; p=0.0006; best cutoff=1843 pg/mL), PCT (AUC=0.844;
      p<0.0001), CRP (AUC=0.701; p=0.0048), and lactate (AUC=0.778; p<0.0001). Multiple
      regression analyses showed independent associations of CRP with diagnosis of
      sepsis, and CRP and lactate with mortality. Increased neutrophils (p=0.002) and
      decreased lymphocytes (p=0.007) and monocytes (p=0.046) were also associated with
      mortality. CONCLUSIONS: Presepsin did not outperform traditional sepsis
      biomarkers in diagnosing sepsis from SIRS and in prognostication of mortality in
      critically ill patients. Presepsin may have a limited adjunct value for both
      diagnosis and an early risk stratification, performing independently of clinical
      illness severity.

PMID- 29176019
TI  - In vitro modulation of the cytochrome P450 and ABCB1/P-glycoprotein activities of
      the aqueous extract of Allophylus cominia (L) Sw. leaves.
AB  - BACKGROUND: The aqueous extract of the Allophylus cominia (L) Sw (Sapindaceae)
      leaves has shown anti-diabetic, anti-obesity and anti-inflammatory properties. In
      the Caribbean region, it is typically used for the treatment of type-2 diabetes.
      METHODS: Considering the herb-drug interaction, the aim of this study was to
      evaluate the potential effects of the A. cominia extract on the cytochrome P450
      (CYP) (rat hepatocyte model) and P-glycoprotein (P-gp) (4T1 cell line) systems.
      RESULTS: The extract did not decrease the cell viability after being assayed by
      the MTT test at up to 1500 MUg/mL for 72 h. The exposure of the cultured rat
      hepatocytes to the product (up to 250 MUg/mL) for 48 h increased the activities
      of CYP-1A2, 2C9, and 2E1 by 1.46-, 1.60-, and 1.51-fold, respectively, compared
      with the controls. The activities of CYP-2B6, 2D6, and 3A4 were not significantly
      altered, whereas the activity of P-gp decreased by 2- and 4-fold. In addition,
      the extracts at 100 and 200 MUg/mL significantly increased doxorubicin
      cytotoxicity in these cells 24 h after treatment. CONCLUSIONS: The findings
      indicate that the A. cominia extract modulates the CYP and P-gp systems
      increasing sensitivity to doxorubicin. Further studies are necessary to evaluate
      the potential herb-drug interaction or chemosensitive properties.

PMID- 29176020
TI  - Antidiarrheal and antimicrobial activities of the ethanol extract from the
      Icacina senegalensis root bark.
AB  - BACKGROUND: The Icacina senegalensis root bark is traditionally used for the
      treatment of gastrointestinal disorders in Nigeria. To date, no scientific study
      has substantiated or refuted this claim. METHODS: The antidiarrheal and
      antimicrobial activities of the ethanol root bark extract were investigated in
      rats and against some selected diarrhea-causing microorganisms. RESULTS: The
      extract significantly decreased the frequency of castor oil-induced diarrhea, and
      inhibited the masses and volumes of intestinal fluid accumulation in the castor
      oil-induced enteropooling method. The distance travelled by the charcoal meal was
      also decreased by the extract gastrointestinal transit method. The extract also
      strongly inhibited the growth of some selected microorganisms. CONCLUSIONS: The
      ethanol extract of the I. senegalensis root bark showed antidiarrheal activity,
      thus justifying its long folkloric use in diarrhea treatment. The extract also
      demonstrated antimicrobial activity against selected diarrheal causing organisms.

PMID- 29176021
TI  - Efficacy and safety of percutaneous administration of dihydrotestosterone in
      children of different genetic backgrounds with micropenis.
AB  - BACKGROUND: Exogenous androgen supplement is an optional treatment for
      micropenis; however, its use in childhood is controversial due to potential side
      effects. METHODS: Twenty-three children (mean age: 4.07+/-3.4 years) with
      micropenis of unknown causes harboring the 46,XY karyotype were recruited in an
      open prospective study. Androgen receptor (AR), steroid 5alpha-reductase-2
      (SRD5A2), and SRY genes were sequenced; 2.5% dihydrotestosterone (DHT)
      transdermal gel (0.1-0.3 mg/kg/day) was applied and titrated within the normal
      DHT serum reference ranges. Stretched penile length (SPL) was measured before
      therapy, and after 1, 3 and 6 months of DHT gel treatment, respectively. RESULTS:
      Two patients were found with AR gene mutations and five patients with SRD5A2 gene
      mutations. Average stretched penile lengths (SPLs) were 1.68+/-0.6 cm at baseline
      and 2.2+/-0.66 cm, 2.6+/-0.59 cm and 2.9+/-0.55 cm (mean +/- 1 SD) after 1, 3 and
      6 months of treatment, respectively. Fourteen cases (61%) reached standard penile
      length ranges (>-2.5 SD) and medication was discontinued; six cases (26%) were
      satisfied with the improved penile lengths despite failing to reach the aged
      matched standards. Three infants (13%) discontinued the medication after 3 months
      due to anxiety about the potential side effects. No significant side effects were
      found except the elevated DHT serum levels after therapy. CONCLUSIONS: Short term
      and local application of DHT at low doses in patients with micropenis could
      accelerate penile growth effectively without evident side effects; however,
      precautions still need be taken due to the paucity of long term study and the
      lack of ideal DHT dosage.

PMID- 29176022
TI  - Mutation analysis of the phenylalanine hydroxylase gene and prenatal diagnosis of
      phenylketonuria in Shaanxi, China.
AB  - BACKGROUND: This study aims to investigate the spectrum and frequency of
      phenylalanine hydroxylase (PAH) gene mutations and the power to prenatally
      diagnose phenylketonuria (PKU) patients in Shaanxi, China. METHODS: Polymerase
      chain reaction (PCR) and DNA sequencing analyses were performed to examine the
      PAH gene in 33 PKU patients and seven amniotic fluid samples. Thirty-four
      pathogenic variants were indicated in all 63 alleles, in which two probands
      carried three variants. RESULTS: Pedigree analysis suggested that the
      [c.158G>A([p.R53H)][IVS7+2T>A] mutation was located at the same chromatid.
      However, there was a controversial viewpoint that thought the c.158G>A(p.R53H)
      variant was a polymorphism in the Chinese. We also found one novel indel mutation
      and identified the c.59_60delAGinsCC mutation of the PAH gene for the very first
      time. The spectrum of the PAH mutations in Shaanxi Province were similar to that
      among China's population. Based on the results of PAH gene analysis, we further
      performed prenatal genetic diagnoses for seven PKU families. All foetuses were
      definitively diagnosed, and their parents were provided with genetic counselling.
      CONCLUSIONS: PAH gene analysis is a crucial method for PKU diagnosis and prenatal
      genetic prognosis, even though many uncommon mutations would affect the analysis
      and diagnosis of genetic abnormalities.

PMID- 29176023
TI  - The role of enterovirus infections in type 1 diabetes in Tunisia.
AB  - BACKGROUND: Enteroviral infections have long been suspected in having a role in
      beta cell destruction and therefore leading to the onset of clinical type 1
      diabetes (T1D). The frequency of enterovirus (EV)-related T1D in North Africa is
      still unknown. The aim of the present study was to investigate the relationship
      between infection with EV and T1D in Tunisia. METHODS: A total of 95 T1D patients
      (41 children and 54 adults) and 141 healthy control subjects (57 children and 84
      adults) were tested for the presence of EV-RNA by a highly sensitive nested
      reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: EV-RNA
      was detected more frequently in plasma from diabetic patients than in plasma of
      controls (31.6% vs. 7.8%, p<0.0001; OR=5.45; 95% CI 2.44-12.43). RT-PCR revealed
      positive in 53.7% of T1D children and 14.8% of T1D adults. There was a
      statistically significant difference between children and adults with T1D
      (p<0.0001). Positivity of EV-RNA according to the time after the occurrence of
      the disease did not show any significant difference (p=0.34). Anti-glutamic acid
      decarboxylase (GAD) antibodies were not associated with EV-RNA (p=0.65).
      CONCLUSIONS: EV-RNA is associated with T1D mellitus in the Tunisian population
      especially in children. These results support the hypothesis that EV act as
      environmental risk factors for T1D.

PMID- 29176024
TI  - How often are clinicians performing genital exams in children with disorders of
      sex development?
AB  - BACKGROUND: We sought to determine the frequency with which genital exams (GEs)
      are performed in children with disorders of sex development (DSD) and ambiguous
      genitalia (AG) during routine visits to the pediatric endocrine clinic. METHODS:
      Medical records of children with DSD and AG seen at one large academic center
      since 2007 were reviewed. Data analyzed included diagnosis, sex of rearing, age,
      initial or follow up visit, number of individuals present and sex of the
      pediatric endocrinologist. Repeated measures analysis was performed to evaluate
      associations between GEs and patient/physician factors. RESULTS: Eighty-two
      children with DSD and AG who had a total of 632 visits were identified. Sex of
      rearing was female in 78% and the most common diagnosis was congenital adrenal
      hyperplasia (CAH) (68%). GEs were performed in 35.6% of visits. GEs were more
      likely in patients with male sex of rearing (odds ratio [OR] 17.81, p=0.006),
      during initial vs. follow-up visits (OR 5.99, p=0.012), and when the examining
      endocrinologist was female (OR 3.71, p=0.014). As patients aged, GEs were less
      likely (OR 0.76, p<0.0001). CONCLUSIONS: GEs were performed in approximately one
      third of clinic visits in children with DSD and AG. Male sex of rearing, initial
      visits and female pediatric endocrinologist were associated with more frequent
      GEs.

PMID- 29176025
TI  - A newborn with combined pituitary hormone deficiency developing shock and sludge.
AB  - A male neonate was born at 41 weeks of gestation with a birth weight of 3320 g.
      Artificial respiratory management was required due to respiratory disturbance 1 h
      after birth, and subsequently catecholamine-refractory low cardiac output-induced
      shock occurred. Severe combined pituitary hormone deficiency (CPHD) was
      considered based on the presence of his respiratory disturbance, hypoglycemia and
      micropenis. After hydrocortisone (HDC) administration, circulatory dynamics
      rapidly improved. Brain magnetic resonance imaging (MRI) showed aplasia of the
      anterior pituitary gland and ectopic posterior gland. gamma
      Glutamyltranspeptidase (gamma-GTP) increased from day 10 after birth and direct
      bilirubin increased from day 18. On ultrasonography, sludge filling the common
      bile duct and gall bladder was observed. After initiating treatment with both
      ursodeoxycholic acid and recombinant human growth hormone (rhGH), cholestasis
      improved and the sludge disappeared at 3 months after birth. In newborns with
      CPHD, severe central adrenal insufficiency might induce cardiogenic shock after
      birth. Early diagnosis and intervention are necessary.

PMID- 29176026
TI  - The use of a radiolucent template to improve bone age X-ray quality (BASIC
      study).
AB  - BACKGROUND: Left hand and wrist X-rays are conventionally used to assess skeletal
      maturity using methods such as Tanner-Whitehouse 3 (TW3). We noted a number were
      poor quality, caused by difficulty with hand placement. We introduced a simple
      radiolucent hand template to assist in hand positioning and assessed changes in X
      ray quality and repeat X-ray rates. METHODS: The position of fingers, thumb and
      overall clarity of bone age X-rays were prospectively scored. In the absence of a
      validated tool to assess quality a 1-3 scale (poor, borderline, good) was
      devised. A radiolucent hand template was introduced for use in the intervention
      group. Need for repeat X-ray was determined by set criteria. RESULTS: The
      intervention improved scores. More patients scored 3 (good) for positioning of
      fingers (89.29% and 85.33%, p=0.38), thumb (98.21% and 89.96%, p=0.06) and
      overall clarity (76.79% and 70.27%, p=0.41) for the intervention (n=56) and
      control groups (n=259), respectively. No patient required repeat X-ray from the
      intervention group, compared with 28 in the control group (p=0.007). CONCLUSIONS:
      Achieving good quality bone age X-rays is more difficult than previously assumed.
      The use of a radiolucent hand template has been shown to improve hand position
      and significantly reduce the need for repeat X-ray.

PMID- 29176027
TI  - Identification of a novel mutation of NR0B1 in a patient with X-linked adrenal
      hypoplasia and symptomatic treatment.
AB  - BACKGROUND: X-linked congenital adrenal hypoplasia (X-linked AHC) is
      characterized by acute onset of primary adrenal insufficiency in infancy or early
      childhood and hypogonadotropic hypogonadism (HH) at puberty. Mutations in NR0B1,
      the gene located on Xp21.3 and encoding an orphan nuclear receptor named DAX1,
      are responsible for this disease. METHODS: The entire coding region of the NR0B1
      gene of a 14-year-old X-linked AHC proband as well as his family members was
      sequenced. Clinical and endocrine evaluations with symptomatic treatment results
      were recorded. RESULTS: DNA sequencing revealed a missense mutation (c.383-384
      insA) in exon 1, which resulted in a novel frameshift mutation, thereby resulting
      in a truncated protein (p.Leu129 Pro fs*137). The therapeutic trail with an
      observation period of 20 weeks showed an effective improvement in symptoms of
      hypogonadism with human chorionic gonadotropin (HCG) administration, including a
      rapid improvement of serum testosterone level, descending of testicles as well as
      enlargement of testicles and growth of penis. CONCLUSIONS: Our study identified a
      novel frameshift mutation of the NR0B1 gene in a proband with X-linked AHC/HH and
      further expanded the number of NR0B1 mutations reported in the literature.
      Moreover, the symptomatic treatment observation provided referential evidence in
      the treatment of X-linked AHC associated hypogonadism and bilateral inguinal
      cryptorchidism.

PMID- 29176028
TI  - Higher phthalate concentrations are associated with precocious puberty in normal
      weight Thai girls.
AB  - BACKGROUND: The cause of precocious puberty may be associated with genetics and
      other conditions such as central nervous system (CNS) insults, or the exposure to
      endocrine disrupting chemicals (EDCs). Phthalates is known to be one of the EDCs
      and have estrogenic and antiandrogenic activities, and may be associated with
      advanced puberty. The objective of the study was to determine the association
      between urinary phthalate metabolites and advanced puberty. METHODS: A cross
      sectional study was conducted in patients with precocious puberty (breast onset
      <8 years, n=42) and early puberty (breast onset 8-9 years, n=17), compared to age
      matched controls (n=77). Anthropometric measurements, estradiol, basal and
      gonadotropin releasing hormone (GnRH)-stimulated follicle stimulating hormone
      (FSH) and luteinizing hormone (LH) levels, uterine sizes, ovarian diameters and
      bone ages (BA) were obtained. Urine samples were collected and mono-methyl
      phthalate (MMP) and mono-ethyl phthalate (MEP) were analyzed by high performance
      liquid chromatography (HPLC) and adjusted with urine creatinine. RESULTS: The
      median adjusted-MEP concentration in girls with precocious puberty, was greater
      than in normal girls (6105.09 vs. 4633.98 MUg/g Cr: p<0.05), and had the same
      trend among early puberty and normal puberty (5141.41 vs. 4633.98 MUg/g Cr:
      p=0.4), but was not statistically significant. CONCLUSIONS: Precocious puberty
      girls had an association with increased MEP concentration. This is the first
      report of the association between urinary phthalate levels and precocious puberty
      in Thai girls.

PMID- 29176030
TI  - Human responses to complex environmental exposures: linking causes and effects.

PMID- 29176029
TI  - Serum progranulin levels in relation to insulin resistance in childhood obesity.
AB  - BACKGROUND: Progranulin is an adipokine that is involved in the inflammatory
      response, glucose metabolism, insulin resistance, and may therefore be involved
      in chronic subclinical inflammation associated with the pathogenesis of childhood
      obesity. We aimed to investigate the association of circulating progranulin
      levels with metabolic parameters in children and to assess the importance of
      progranulin as a biomarker for metabolic diseases. METHODS: A total of 150
      children were consecutively recruited from the Pediatric Nutrition Clinics at
      King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Children were
      classified into four groups based on quartile for serum progranulin.
      Anthropometric variables were measured in all study subjects. Fasting blood
      samples were collected for measurement of blood glucose, insulin and lipid
      profile. RESULTS: Children within the upper quartile for serum progranulin
      concentration were heavier, more insulin resistant and had higher concentrations
      of serum total cholesterol, triglycerides, insulin and high sensitivity C
      reactive protein compared to those in the lower quartile. On correlation
      analysis, serum progranulin concentrations were significantly related to general
      and central adiposity, metabolic parameters, markers of inflammation and insulin
      resistance. Stepwise multiple regression showed that 26.6% of the variability in
      serum progranulin could be explained by measures of adiposity. CONCLUSIONS: The
      increased serum progranulin concentrations were closely related to measures of
      adiposity, metabolic parameters, inflammatory marker and insulin resistance
      indices, suggesting that progranulin may be an excellent biomarker for obesity in
      childhood.

PMID- 29176031
TI  - The neurophysiology of working memory development: from childhood to adolescence
      and young adulthood.
AB  - Working memory (WM) is an important cognitive function that is necessary to
      perform our daily activities. The present review briefly describes the most
      accepted models underlying WM and the neural networks involved in its processing.
      The review focuses on how the neurophysiological mechanisms develop with age in
      the periods from childhood to adolescence and young adulthood. Studies using
      behavioral, neuroimaging, and electrophysiological techniques showed the progress
      of WM throughout the development. The present review focuses on the
      neurophysiology of the basic processes underlying WM operations, as indicated by
      electroencephalogram-derived signals, in order to take advantage of the excellent
      time resolution of this technique. Children and adults use similar cerebral
      mechanisms and areas to encode, recognize, and keep the stimuli in memory and
      update the WM contents, although adults rely more on anterior sites. The
      possibility that a functional reorganization of WM brain processing occurs around
      the adolescent period is suggested, and would partly justify the high prevalence
      of the emergence of mental pathology in the adolescent period.

PMID- 29176032
TI  - Predictive validity of pre-admission assessments on medical student performance.
AB  - Objectives: To examine the predictive validity of pre-admission variables on
      students' performance in a medical school in Saudi Arabia. Methods: In this
      retrospective study, we collected admission and college performance data for 737
      students in preclinical and clinical years. Data included high school scores and
      other standardized test scores, such as those of the National Achievement Test
      and the General Aptitude Test. Additionally, we included the scores of the Test
      of English as a Foreign Language (TOEFL) and the International English Language
      Testing System (IELTS) exams. Those datasets were then compared with college
      performance indicators, namely the cumulative Grade Point Average (cGPA) and
      progress test, using multivariate linear regression analysis. Results: In
      preclinical years, both the National Achievement Test (p=0.04, B=0.08) and TOEFL
      (p=0.017, B=0.01) scores were positive predictors of cGPA, whereas the General
      Aptitude Test (p=0.048, B=-0.05) negatively predicted cGPA. Moreover, none of the
      pre-admission variables were predictive of progress test performance in the same
      group. On the other hand, none of the pre-admission variables were predictive of
      cGPA in clinical years. Overall, cGPA strongly predict-ed students' progress test
      performance (p<0.001 and B=19.02). Conclusions: Only the National Achievement
      Test and TOEFL significantly predicted performance in preclinical years. However,
      these variables do not predict progress test performance, meaning that they do
      not predict the functional knowledge reflected in the progress test. We report
      various strengths and deficiencies in the current medical college admission
      criteria, and call for employing more sensitive and valid ones that predict
      student performance and functional knowledge, especially in the clinical years.

PMID- 29176033
TI  - TNFalpha-senescence initiates a STAT-dependent positive feedback loop, leading to
      a sustained interferon signature, DNA damage, and cytokine secretion.
AB  - Cellular senescence is a cell fate program that entails essentially irreversible
      proliferative arrest in response to damage signals. Tumor necrosis factor-alpha
      (TNFalpha), an important pro-inflammatory cytokine secreted by some types of
      senescent cells, can induce senescence in mouse and human cells. However,
      downstream signaling pathways linking TNFalpha-related inflammation to senescence
      are not fully characterized. Using human umbilical vein endothelial cells
      (HUVECs) as a model, we show that TNFalpha induces permanent growth arrest and
      increases p21CIP1, p16INK4A, and SA-beta-gal, accompanied by persistent DNA
      damage and ROS production. By gene expression profiling, we identified the
      crucial involvement of inflammatory and JAK/STAT pathways in TNFalpha-mediated
      senescence. We found that TNFalpha activates a STAT-dependent autocrine loop that
      sustains cytokine secretion and an interferon signature to lock cells into
      senescence. Furthermore, we show STAT1/3 activation is necessary for cytokine and
      ROS production during TNFalpha-induced senescence. However, inhibition of STAT1/3
      did not rescue cells from proliferative arrest, but rather suppressed cell cycle
      regulatory genes and altered TNFalpha-induced senescence. Our findings suggest a
      positive feedback mechanism via the STAT pathway that sustains cytokine
      production and reveal a reciprocal regulatory role of JAK/STAT in TNFalpha
      mediated senescence.

PMID- 29176034
TI  - Selenium preserves keratinocyte stemness and delays senescence by maintaining
      epidermal adhesion.
AB  - Skin is constantly exposed to environmental factors such as pollutants, chemicals
      and ultra violet radiation (UV), which can induce premature skin aging and
      increase the risk of skin cancer. One strategy to reduce the effect of oxidative
      stress produced by environmental exposure is the application of antioxidant
      molecules. Among the endogenous antioxidants, selenoproteins play a key role in
      antioxidant defense and in maintaining a reduced cellular environment. Selenium,
      essential for the activity of selenoproteins, is a trace element that is not
      synthesized by organisms and must be supplied by diet or supplementation. The aim
      of this study is to evaluate the effect of Selenium supplementation on skin
      aging, especially on keratinocytes, the main cells of the epidermis. Our results
      demonstrate for the first time to our knowledge, the major role of Selenium on
      the replicative life span of keratinocytes and on aging skin. Selenium protects
      keratinocyte stem cells (KSCs) against senescence via preservation of their
      stemness phenotype through adhesion to the basement membrane. Additionally,
      Selenium supplementation maintains the homeostasis of skin during chronological
      aging in our senescent skin equivalent model. Controlled supplementation with
      Selenium could be a new strategy to protect skin against aging.

PMID- 29176036
TI  - One-step delivery of a functional multi-layered cell sheet using a thermally
      expandable hydrogel with controlled presentation of cell adhesive proteins.
AB  - In this study, we developed a new system enabling rapid delivery of a multi
      layered cell sheet by combining layer-by-layer (LBL) coating of a cell membrane
      and surface engineered thermally expandable hydrogel. Human dermal fibroblasts
      were LBL-coated with fibronectin (FN) and gelatin to form a multi-layered cell
      sheet in a single seeding step via spontaneous 3D cell-cell interactions. FN was
      covalently immobilized onto the surface of a Tetronic(r)-based hydrogel at two
      different concentrations (1 and 5 MUg ml-1) for stable adhesion of the multi
      layered cell sheet, followed by polydopamine coating. In both conditions, a multi
      layered cell sheet was stably formed. Then, the cell sheet on the hydrogel
      modified with 1 MUg ml-1 FN rapidly detached (>90% efficiency) in response to the
      expansion of the hydrogel when temperature changed from 37  degrees C to 4 
      degrees C, while the other group had a reduced detachment due to excessive cell
      hydrogel interaction. The multi-layered cell sheet was evident in cell
      extracellular matrix and cell-cell junction formation, and bFGF was continuously
      secreted over 7 days of in vitro culture. The multi-layered transplanted to the
      mouse subcutaneous tissue also exhibited evidence of vascular ingrowth, which
      collectively suggest that the delivery system maintaining cellular functions is
      applicable for regenerative medicine.

PMID- 29176035
TI  - Coaxial extrusion bioprinting of 3D microfibrous constructs with cell-favorable
      gelatin methacryloyl microenvironments.
AB  - Bioinks with shear-thinning/rapid solidification properties and strong mechanics
      are usually needed for the bioprinting of three-dimensional (3D) cell-laden
      constructs. As such, it remains challenging to generate soft constructs from
      bioinks at low concentrations that are favorable for cellular activities. Herein,
      we report a strategy to fabricate cell-laden constructs with tunable 3D
      microenvironments achieved by bioprinting of gelatin methacryloyl
      (GelMA)/alginate core/sheath microfibers, where the alginate sheath serves as a
      template to support and confine the GelMA pre-hydrogel in the core during the
      extrusion process, allowing for subsequent UV crosslinking. This novel strategy
      minimizes the bioprinting requirements for the core bioink, and facilitates the
      fabrication of cell-laden GelMA constructs at low concentrations. We first showed
      the capability of generating various alginate hollow microfibrous constructs
      using a coaxial nozzle setup, and verified the diffusibility and perfusability of
      the bioprinted hollow structures that are important for the tissue engineering
      applications. More importantly, the hollow alginate microfibers were then used as
      templates for generating cell-laden GelMA constructs with soft microenvironments,
      by using GelMA pre-hydrogel as the bioink for the core phase during bioprinting.
      As such, GelMA constructs at extremely low concentrations (<2.0%) could be
      extruded to effectively support cellular activities including proliferation and
      spreading for various cell types. We believe that our strategy is likely to
      provide broad opportunities in bioprinting of 3D constructs with cell-favorable
      microenvironments for applications in tissue engineering and pharmaceutical
      screening.

PMID- 29176037
TI  - Quantitative analysis of charge trapping and classification of sub-gap states in
      MoS2 TFT by pulse I-V method.
AB  - The threshold voltage instabilities and huge hysteresis of MoS2 thin film
      transistors (TFTs) have raised concerns about their practical applicability in
      next-generation switching devices. These behaviors are associated with charge
      trapping, which stems from tunneling to the adjacent trap site, interfacial redox
      reaction and interface and/or bulk trap states. In this report, we present
      quantitative analysis on the electron charge trapping mechanism of MoS2 TFT by
      fast pulse I-V method and the space charge limited current (SCLC) measurement. By
      adopting the fast pulse I-V method, we were able to obtain effective mobility. In
      addition, the origin of the trap states was identified by disassembling the sub
      gap states into interface trap and bulk trap states by simple extraction
      analysis. These measurement methods and analyses enable not only quantitative
      extraction of various traps but also an understanding of the charge transport
      mechanism in MoS2 TFTs. The fast I-V data and SCLC data obtained under various
      measurement temperatures and ambient show that electron transport to neighboring
      trap sites by tunneling is the main charge trapping mechanism in thin-MoS2 TFTs.
      This implies that interfacial traps account for most of the total sub-gap states
      while the bulk trap contribution is negligible, at approximately 0.40% and 0.26%
      in air and vacuum ambient, respectively. Thus, control of the interface trap
      states is crucial to further improve the performance of devices with thin
      channels.

PMID- 29176038
TI  - The effect of age on balancing behavior: complexity analysis of mediolateral
      force trajectories.
AB  - OBJECTIVE: We quantified, via complexity analysis, the postural stability of
      healthy people from a wide age range. APPROACH: Thirty-five healthy people aged
      18-72 performed three tasks while balancing on one foot on a force plate:
      standard balancing task, mental task (balancing while answering basic arithmetic
      questions), and knot-tying task (balancing while tying two knots in a piece of
      ribbon). Mediolateral force trajectories were analyzed to determine control
      strategy via Hurst exponents, Lyapunov exponents, Kolmogorov complexity, root
      mean square, and phase-space plots. MAIN RESULTS: We found increased pattern
      repetition in balancing with increased age, as evidenced by the emergence of a
      double attractor pattern in phase-space plots and the increase of Hurst exponents
      with age from approximately 0.3 to 0.8. SIGNIFICANCE: As people age, they tend to
      develop strong feed-forward control strategies for balancing, and lose the
      complexity of micro movements intrinsic to young age. There is an open-loop
      control strategy for balancing that emerges in older adulthood, and there are
      attractors inherent to balancing which begin to develop in middle age.

PMID- 29176039
TI  - Diffusion tensor optical coherence tomography.
AB  - In situ measurements of diffusive particle transport provide insight into tissue
      architecture, drug delivery, and cellular function. Analogous to diffusion-tensor
      magnetic resonance imaging (DT-MRI), where the anisotropic diffusion of water
      molecules is mapped on the millimeter scale to elucidate the fibrous structure of
      tissue, here we propose diffusion-tensor optical coherence tomography (DT-OCT)
      for measuring directional diffusivity and flow of optically scattering particles
      within tissue. Because DT-OCT is sensitive to the sub-resolution motion of
      Brownian particles as they are constrained by tissue macromolecules, it has the
      potential to quantify nanoporous anisotropic tissue structure at micrometer
      resolution as relevant to extracellular matrices, neurons, and capillaries. Here
      we derive the principles of DT-OCT, relating the detected optical signal from a
      minimum of six probe beams with the six unique diffusion tensor and three flow
      vector components. The optimal geometry of the probe beams is determined given a
      finite numerical aperture, and a high-speed hardware implementation is proposed.
      Finally, Monte Carlo simulations are employed to assess the ability of the
      proposed DT-OCT system to quantify anisotropic diffusion of nanoparticles in a
      collagen matrix, an extracellular constituent that is known to become highly
      aligned during tumor development.

PMID- 29176041
TI  - Positioning of head and neck patients for proton therapy using proton range
      probes: a proof of concept study.
AB  - To exploit the full potential of proton therapy, accurate and on-line methods to
      verify the patient positioning and the proton range during the treatment are
      desirable. Here we propose and validate an innovative technique for determining
      patient misalignment uncertainties through the use of a small number of low dose,
      carefully selected proton pencil beams ('range probes') (RP) with sufficient
      energy that their residual Bragg peak (BP) position and shape can be measured on
      exit. Since any change of the patient orientation in relation to these beams will
      result in changes of the density heterogeneities through which they pass, our
      hypothesis is that patient misalignments can be deduced from measured changes in
      Bragg curve (BC) shape and range. As such, a simple and robust methodology has
      been developed that estimates average proton range and range dilution of the
      detected residual BC, in order to locate range probe positions with optimal
      prediction power for detecting misalignments. The validation of this RP based
      approach has been split into two phases. First we retrospectively investigate its
      potential to detect translational patient misalignments under real clinical
      conditions. Second, we test it for determining rotational errors of an
      anthropomorphic phantom that was systematically rotated using an in-house
      developed high precision motion stage. Simulations of RPs in these two scenarios
      show that this approach could potentially predict translational errors to lower
      than1.5 mm and rotational errors to smaller than 1 degrees  using only three or
      five RPs positions respectively.

PMID- 29176040
TI  - Characteristic impedance: frequency or time domain approach?
AB  - OBJECTIVE: Characteristic impedance (Zc) is an important component in the theory
      of hemodynamics. It is a commonly used metric of proximal arterial stiffness and
      pulse wave velocity. Calculated using simultaneously measured dynamic pressure
      and flow data, estimates of characteristic impedance can be obtained using
      methods based on frequency or time domain analysis. Applications of these methods
      under different physiological and pathological conditions in species with
      different body sizes and heart rates show that the two approaches do not always
      agree. In this study, we have investigated the discrepancies between frequency
      and time domain estimates accounting for uncertainties associated with
      experimental processes and physiological conditions. APPROACH: We have used
      published data measured in different species including humans, dogs, and mice to
      investigate: (a) the effects of time delay and signal noise in the pressure-flow
      data, (b) uncertainties about the blood flow conditions, (c) periodicity of the
      cardiac cycle versus the breathing cycle, on the frequency and time domain
      estimates of Zc, and (d) if discrepancies observed under different hemodynamic
      conditions can be eliminated. Main results and Significance: We have shown that
      the frequency and time domain estimates are not equally sensitive to certain
      characteristics of hemodynamic signals including phase lag between pressure and
      flow, signal to noise ratio and the end of systole retrograde flow. The
      discrepancies between two types of estimates are inherent due to their
      intrinsically different mathematical expressions and therefore it is impossible
      to define a criterion to resolve such discrepancies. Considering the
      interpretation and role of Zc as an important hemodynamic parameter, we suggest
      that the frequency and time domain estimates should be further assessed as two
      different hemodynamic parameters in a future study.

PMID- 29176042
TI  - Perfect transmission of 3D massive Kane fermions in HgCdTe Veselago lenses.
AB  - The transmission properties of three-dimensional (3D) massive Kane fermions in
      HgCdTe (MCT) heterojunctions have been studied using the simplified Kane-Mele
      model. Based on our theoretical calculations, we propose the design of an
      electronic device, called a mass inverter, which consists of the junction of a
      narrow-gap semiconductor and semimetal. Such a device can be used in electron
      optics applications, since it operates as a Veselago lens and presents Klein
      tunneling (KT) of 3D massive Kane fermions under normal incidence. We found that
      KT and Veselago lensing can also be observed for general MCT heterojunctions with
      a specific value of doping level. We show that non-resonant perfect transmission
      of massive Kane fermions persists in a potential barrier for heterojunctions
      formed by a semimetal between two standard semiconductors. This effect is quite
      robust when the ideal conditions of a possible experimental test are deviated.
      Our findings may have important implications in the development of nano
      electronic devices using 3D massive Kane fermions, where transmission features of
      massless particles are recovered.

PMID- 29176043
TI  - Sympodial tree-like structures: from small to large-amplitude vibrations.
AB  - This study deals with tree-like structures that mimic a trunk with either first
      order branches or both first and second-order branches of a sympodial tree. The
      corresponding mechanical model comprises physical pendula coupled with torsional
      springs and viscous dampers. Natural frequencies and modal shapes are obtained
      analytically and the effects of a branching angle and a stiffness ratio on their
      change is analysed. Then, the trunk is harmonically excited and the corresponding
      structural response is investigated, both for small undamped and damped
      vibrations, focusing on the concept of dynamic absorbers and the attenuation of
      the amplitude of the trunk and first-order branches as this attenuation is
      beneficial for practical engineering applications. The corresponding frequencies
      at which these amplitudes are equal to zero or in resonance are determined.
      Finally, free large-amplitude vibrations are examined. Conditions for internal
      resonances in the structure with first-order branching are determined
      analytically by using the method of multiple scales. Frequency spectra of large
      amplitude vibrations are obtained numerically focusing on the influence of the
      branching angle on their content. Biomimetic potentials and advantages of
      designing these coupled branched structures are discussed through the whole study
      via the influence of the stiffness ratio of the springs, the branching angle and
      the hierarchy of branches on their response.

PMID- 29176044
TI  - Surface development of a brazing alloy during heat treatment-a comparison between
      UHV and APXPS.
AB  - In an attempt to bridge the pressure gap, APXPS was used to follow the surface
      development of an aluminum brazing sheet during heating in an ambient oxygen
      pressure mimicking the environment of an industrial brazing furnace. The studied
      aluminum alloy brazing sheet is a composite material consisting of two aluminum
      alloy standards whose surface is covered with a native aluminum oxide film. To
      emphasize the necessity of studies of this system in ambient sample environments
      it is compared to measurements in UHV. Changes in thickness and composition of
      the surface oxide were followed after heating to 300  degrees C, 400  degrees C,
      and 500  degrees C. The two sets presented in this paper show that the surface
      development strongly depends on the environment the sample is heated in.

PMID- 29176045
TI  - Thermal annealing and pressure effects on BaFe<sub>2
      <i>x</i></sub>Co<sub><i>x</i></sub>As<sub>2</sub> single crystals.
AB  - We investigate the pressure and thermal annealing effects on BaFe<sub>2
      <i>x</i></sub>Co<sub><i>x</i></sub>As<sub>2</sub> (Co-Ba122) single crystals with
      <i>x</i> = 0.1 and 0.17 via electrical transport measurements. The thermal
      annealing treatment not only enhances the superconducting transition temperature
      (<i>T</i><sub>c</sub>) from 9.6 to 12.7 K for <i>x</i> = 0.1 and from 18.1 to
      21.0 K for <i>x</i> = 0.17, but also increases the antiferromagnetic transition
      temperature (<i>T</i><sub>N</sub>). Simultaneous enhancement of
      <i>T</i><sub>c</sub> and <i>T</i><sub>N</sub> by the thermal annealing treatment
      indicates that thermal annealing could substantially improve the quality of the
      Co-doped Ba122 samples. Interestingly, <i>T</i><sub>c</sub> of the Co-Ba122
      compounds shows a scaling behavior with a linear dependence on the resistivity
      value at 290 K, irrespective of tuning parameters, such as chemical doping,
      pressure, and thermal annealing. These results not only provide an effective way
      to access the intrinsic properties of the BaFe<sub>2</sub>As<sub>2</sub> system,
      but also may shed a light on designing new materials with higher superconducting
      transition temperature.

PMID- 29176046
TI  - Lanthanide stannate pyrochlores (Ln2Sn2O7; Ln  =  Nd, Gd, Er) at high pressure.
AB  - Lanthanide stannate pyrochlores (Ln2Sn2O7; Ln  =  Nd, Gd, and Er) were
      investigated in situ to 50 GPa in order to determine their structural response to
      compression and compare their response to that of lanthanide titanate, zirconate,
      and hafnate pyrochlores. The cation radius ratio of A3+/B4+ in pyrochlore oxides
      (A2B2O7) is thought to be the dominant feature that influences their response on
      compression. The ionic radius of Sn4+ is intermediate to that of Ti4+, Zr4+, and
      Hf4+, but the <Sn-O> bond in stannate pyrochlore is more covalent than the <B-O>
      bonds in titanates, zirconate, and hafnates. In stannates, based on in situ Raman
      spectroscopy, pyrochlore cation and anion sublattices begin to disorder with the
      onset of compression, first measured at 0.3 GPa. The extent of sublattice
      disorder versus pressure is greater in stannates with a smaller Ln3+ cation.
      Stannate pyrochlores (Fd-3m) begin a sluggish transformation to an orthorhombic,
      cotunnite-like structure at ~28 GPa; similar transitions have been observed in
      titanate, zirconate, and hafnate pyrochlores at varying pressures (18-40 GPa)
      with cation radius ratio. The extent of the phase transition versus pressure
      varies directly with the size of the Ln3+ cation. Post-decompression from ~50
      GPa, Er2Sn2O7 and Gd2Sn2O7 adopt a pyrochlore structure, rather than the multi
      scale defect-fluorite  +  weberite-type structure adopted by Nd2Sn2O7 that is
      characteristic of titanate, zirconate, and hafnate pyrochlores under similar
      conditions. Like pyrochlore titanates, zirconates, and hafnates, the bulk
      modulus, B 0, of stannates varies linearly and inversely with cation radius ratio
      from 1 1 1 GPa (Nd2Sn2O7) to 251 GPa (Er2Sn2O7). The trends of bulk moduli in
      stannates in this study are in excellent agreement with previous experimental
      studies on stannates and suggest that the size of the Ln3+ cation is the primary
      determining factor of B 0. Additionally, when normalized to r A/r B, the bulk
      moduli of stannates are comparable to those of zirconates and hafnates, which
      vary from titanates. Our results suggest that the cation radius ratio strongly
      influences the bulk moduli of stannates, as well as their overall compression
      response.

PMID- 29176047
TI  - Macro-mechanics controls quantum mechanics: mechanically controllable quantum
      conductance switching of an electrochemically fabricated atomic-scale point
      contact.
AB  - Here, we present a silver atomic-scale device fabricated and operated by a
      combined technique of electrochemical control (EC) and mechanically controllable
      break junction (MCBJ). With this EC-MCBJ technique, we can perform mechanically
      controllable bistable quantum conductance switching of a silver quantum point
      contact (QPC) in an electrochemical environment at room temperature. Furthermore,
      the silver QPC of the device can be controlled both mechanically and
      electrochemically, and the operating mode can be changed from 'electrochemical'
      to 'mechanical', which expands the operating mode for controlling QPCs. These
      experimental results offer the perspective that a silver QPC may be used as a
      contact for a nanoelectromechanical relay.

PMID- 29176048
TI  - Enhanced photocatalytic water-splitting performance using Fe-doped hierarchical
      TiO2 ball-flowers.
AB  - The photocatalytic water-splitting behavior of hierarchically structured TiO2
      ball-flowers with different Fe ion contents was studied, in order to elucidate
      the effects of Fe doping on their water-splitting performance. It was found that
      with the increase of Fe doping content, the hydrogen evolution rate increased
      initially and then decreased. The highest hydrogen evolution of 697 MUmol g-1 is
      observed for 2Fe/TiO2, after 4 h of light irradiation, which was five times
      greater than that in the case of pure TiO2 who has 140 MUmol g-1 hydrogen
      evolution after 4 h of light irradiation. This improvement in the water-splitting
      efficiency owing to optimized Fe doping could be attributed to an enhancement in
      the visible-light absorption characteristics and an increase in the number of
      oxygen vacancies, which act as the reaction sites for water splitting.

PMID- 29176049
TI  - Flexible robust binder-free carbon nanotube membranes for solid state and
      microcapacitor application.
AB  - We present a liquid phase post synthesis self-assemble protocol that transforms
      trillions of carbon nanotubes (CNTs) in powder form into densely packed flexible,
      robust and binder-free macroscopic membranes with a hierarchical pore structure.
      We employ charge transfer engineering to spontaneously disperse the CNTs in a
      liquid medium. The processing protocol has limited or no impact on the intrinsic
      properties of the CNTs. As the thickness of the CNT membrane is increased, we
      observed a gradual transition from high flexibility to buckling and brittleness
      in the flexural properties of the membranes. The binder-free CNT membranes have
      bulk mass density greater than that of water (1.0 g cm-3). We correlate the mass
      of the CNTs in the membrane to the thickness of the membrane and obtained a bulk
      mass density of ~1.11 g cm-3 +/- 0.03 g cm-3. We demonstrate the use of the CNT
      membranes as electrode in a pristine and oxidized single/stacked solid-state
      capacitor as well as pristine interdigitated microcapacitor that show time
      constant of ~32 ms with no degradation in performance even after 10 000 cycles.
      The capacitors show very good temperature dependence over a wide range of
      temperatures with good cycling performance up to 90  degrees C. The specific
      capacitance of the pseudocapacitive CNT electrode at room temperature was 72 F g
      1 and increased to 100 F g-1 at 70  degrees C. The leakage current of bipolar
      stacked solid state capacitor was ~100 nA cm-2 at 2.5 V when held for 72 h.

PMID- 29176050
TI  - Visible light-induced electronic structure modulation of Nb- and Ta-doped alpha
      Fe2O3 nanorods for effective photoelectrochemical water splitting.
AB  - The photoelectrochemical (PEC) water splitting activity of Nb and Ta-doped
      hematite (alpha-Fe2O3) nanorods was investigated with reference to electronic
      structures by in situ synchrotron x-ray absorption spectroscopy (XAS). Current
      density-potential measurements demonstrate that the PEC activity of alpha-Fe2O3
      nanorods depends strongly on the species and concentrations of dopants. The
      doping of alpha-Fe2O3 nanorods with a low level of Nb or Ta can improve their
      electrical conductivity and thereby facilitate charge transport and reduced
      electron-hole recombination therein. The photoconversion effects of Nb and Ta
      doped alpha-Fe2O3 by in situ XAS in the dark and under illumination revealed
      opposite evolutions of the spectral intensities of the Fe L-edge and Nb/Ta L
      edge, indicating that charge transfer and a conduction pathway are involved in
      the photoconversion. Analytic in situ XAS results reveal that the alpha-Fe2O3
      that is doped with a low level of Nb has a greater photoconversion efficiency
      than that doped with Ta because Nb sites are more active than Ta sites in alpha
      Fe2O3. The correlation between PEC activity and the electronic structure of Nb/Ta
      doped alpha-Fe2O3 is examined in detail using in situ XAS and helps to elucidate
      the mechanism of PEC water splitting in terms of the electronic structure.

PMID- 29176051
TI  - Polymer-based doping control for performance enhancement of wet-processed short
      channel CNTFETs.
AB  - The electrical transport properties of short-channel transistors based on single
      walled carbon nanotubes (CNT) are significantly affected by bundling along with
      solution processing. We report that especially high off currents of CNT
      transistors are not only related to the incorporation of metallic CNTs but also
      to the incorporation of CNT bundles. By applying device passivation with poly(4
      vinylpyridine), the impact of CNT bundling on the device performance can be
      strongly reduced due to increased gate efficiency as well as reduced oxygen and
      water-induced p-type doping, boosting essential field-effect transistor
      performance parameters by several orders of magnitude. Moreover, this passivation
      approach allows the hysteresis and threshold voltage of CNT transistors to be
      tuned.

PMID- 29176053
TI  - Retardation effects on the dispersion and propagation of plasmons in metallic
      nanoparticle chains.
AB  - We consider a chain of regularly-spaced spherical metallic nanoparticles, where
      each particle supports three degenerate localized surface plasmons. Due to the
      dipolar interaction between the nanoparticles, the localized plasmons couple to
      form extended collective modes. Using an open quantum system approach in which
      the collective plasmons are interacting with vacuum electromagnetic modes and
      which, importantly, readily incorporates retardation via the light-matter
      coupling, we analytically evaluate the resulting radiative frequency shifts of
      the plasmonic bandstructure. For subwavelength-sized nanoparticles, our
      analytical treatment provides an excellent quantitative agreement with the
      results stemming from laborious numerical calculations based on fully-retarded
      solutions to Maxwell's equations. Indeed, the explicit expressions for the
      plasmonic spectrum which we provide showcase how including retardation gives rise
      to a logarithmic singularity in the bandstructure of transverse-polarized
      plasmons. We further study the impact of retardation effects on the propagation
      of plasmonic excitations along the chain. While for the longitudinal modes,
      retardation has a negligible effect, we find that the retarded dipolar
      interaction can significantly modify the plasmon propagation in the case of
      transverse-polarized modes. Moreover, our results elucidate the analogy between
      radiative effects in nanoplasmonic systems and the cooperative Lamb shift in
      atomic physics.

PMID- 29176052
TI  - Development of a dual-ended readout detector with segmented crystal bars made
      using a subsurface laser engraving technique.
AB  - Depth of interaction (DOI) information is indispensable to improving the
      sensitivity and spatial resolution of positron emission tomography (PET) systems,
      especially for small field-of-view PET such as small animal PET and human brain
      PET. We have already developed a series of X'tal cube detectors for isotropic
      spatial resolution and we obtained the best isotropic resolution of 0.77 mm for
      detectors with six-sided readout. However, it is still challenging to apply the
      detector for PET systems due to the high cost of six-sided readout electronics
      and carrying out segmentation of a monolithic cubic scintillator in three
      dimensions using the subsurface laser engraving (SSLE) technique. In this work,
      we propose a more practical X'tal cube with a two-sided readout detector, which
      is made of crystal bars segmented in the height direction only by using the SSLE
      technique. We developed two types of prototype detectors with a 3 mm cubic
      segment and a 1.5 mm cubic segment by using 3  *  3  *  20 mm3 and 1.5  *  1.5  *
      20 mm3 crystal bars segmented into 7 and 13 DOI segments, respectively, using
      the SSLE technique. First, the performance of the detector, composed of one
      crystal bar with different DOI segments and two thorough silicon via (TSV) multi
      pixel photon counters (MPPCs) as readout at both ends of the crystal bar, were
      evaluated in order to demonstrate the capability of the segmented crystal bars as
      a DOI detector. Then, performance evaluation was carried out for a 4  *  4
      crystal array of 3  *  3  *  20 mm3 with 7 DOI segments and an 8  *  8 crystal
      array of 1.5  *  1.5  *  20 mm3 with 13 DOI segments. Each readout included a 4 
      *  4 channel of the 3  *  3 mm2 active area of the TSV MPPCs. The three
      dimensional position maps of the detectors were obtained by the Anger-type
      calculation. All the segments in the 4  *  4 array were identified very clearly
      when there was air between the crystal bars, as each crystal bar was coupled to
      one channel of the MPPCs; however, it was necessary to optimize optical
      conditions between crystal bars for the 8  *  8 array because of light sharing
      between crystal bars coupled to one channel of the MPPCs. The optimization was
      performed for the 8  *  8 array by inserting reflectors fully or partially
      between the crystal bars and the best crystal identification performance was
      obtained with the partial reflectors between the crystal bars. The mean energy
      resolutions at the 511 keV photo peak for the 4  *  4 array with air between the
      crystal bars and for the 8  *  8 array with partial reflectors between the
      crystal bars were 10.1%  +/-  0.3% and 10.8%  +/-  0.8%, respectively. Timing
      resolutions of 783  +/-  36 ps and 1.14  +/-  0.22 ns were obtained for the
      detectors composed of the 4  *  4 array and the 8  *  8 array with partial
      reflectors, respectively. These values correspond to single photon timing
      resolutions. Practical X'tal cubes with 3 mm and 1.5 mm DOI resolutions and two
      sided readout were developed.

PMID- 29176054
TI  - Synthesis of thiolated arabinoxylan and its application as sustained release
      mucoadhesive film former.
AB  - The present work aimed to synthesize thiolated arabinoxylan (TAX), and to
      evaluate its mucoadhesive potential. Synthesis of TAX was accomplished by
      esterification of arabinoxylan (AX) with thioglycolic acid (TGA). The appearance
      of a characteristic peak at 2516 cm-1 in the FTIR spectrum of TAX, and presence
      of 6.01 +/- 1.03 m moles of thiol per gram of the polymer confirmed successful
      thiolation of AX. The incorporation of the thiol group considerably promoted
      mucoadhesive strength of the polymer-viz. 3.99-fold. Moreover, in vivo safety
      analysis in albino rats revealed TAX to be safe in the concentration range of 750
      1000 mg kg-1 body weight. Synthesized TAX was utilized to prepare Tizanidine HCl
      (TZN HCl) loaded sustained release (SR) mucoadhesive buccal films using a solvent
      casting technique. Results proved that the prepared films were of uniform
      thickness, good mechanical strength (with folding endurance >300), acceptable
      moisture contents (5%-7%) and surface pH (6.23 +/- 0.81 to 6.43 +/- 0.49)
      compatible to that of the buccal cavity. Presence of greater that 90% of drug
      contents indicated the excellent drug loading ability of the prepared films.
      Results of in vitro dissolution studies and ex vivo permeation studies conducted
      respectively by USP dissolution apparatus II and Franz diffusion cell indicated
      that sustained effect of TAX was achieved for 8 h. These results have
      conclusively proven that TAX has the potential to improve the bioavailability of
      TZN HCl due to enhanced mucoadhesion in buccal cavity, hence signifying its
      suitability as a mucoadhesive buccal film former.

PMID- 29176055
TI  - Multiscale assembly of solution-processed organic electronics: the critical roles
      of confinement, fluid flow, and interfaces.
AB  - Organic semiconducting small molecules and polymers provide a rich phase space
      for investigating the fundamentals of molecular and hierarchical assembly.
      Stemming from weak intermolecular interactions, their assembly sensitively
      depends on processing conditions, which in turn drastically modulate their
      electronic properties. Much work has gone into molecular design strategies that
      maximize intermolecular interactions and encourage close packing. Less
      understood, however, is the non-equilibrium assembly that occurs during the
      fabrication process (especially solution coating and printing) which is critical
      to determining thin film morphology across length scales. This encompasses
      polymorphism and molecular packing at molecular scale, assembly of pi-bonding
      aggregates at the tens of nanometers scale, and the formation of domains at the
      micron-millimeter device scale. Here, we discuss three phenomena ubiquitous in
      solution processing of organic electronic thin films: the confinement effect,
      fluid flows, and interfacial assembly and the role they play in directing
      assembly. This review focuses on the mechanistic understanding of how assembly
      outcomes couple closely to the solution processing environment, supported by
      salient examples from the recent literature.

PMID- 29176056
TI  - Calculation of the exposure buildup factors for X-ray photons with continuous
      energy spectrum by Monte Carlo code.
AB  - The exposure buildup factors are very important for the calculation of radiation
      shielding and also applied radiation. We must distinguish the monoenergetic and
      continuous energy spectrum gamma source in order to calculate the exposure
      buildup factors. In this study, the exposure buildup factors for two X-ray
      continuous energy spectrum (bremsstrahlung) with 5 and 10 MeV endpoint energy
      were calculated up to depths 10 mfp of water. It was observed that there is a
      large difference between the obtained exposure buildup factors due to the
      monoenergetic and continuous energy spectrum gamma source. The calculation
      results show that the relative differences in 5 MeV energy for 1 mfp to 10 mfp
      are 114% to 44%, respectively, and also the relative differences in 10 MeV energy
      for 1 mfp to 10 mfp are 87% to 38%, respectively. Actually, the main purpose of
      this paper is to illustrate the fact that there is a significant difference
      between the exposure buildup factor due to the continuous and monoenergetic gamma
      source. Therefore, radiation staffs must pay more attention to calculate the
      thickness of the radiation shields for continuous energy gamma source.

PMID- 29176058
TI  - Self-organized nanocrack networks: a pathway to enlarge catalytic surface area in
      sputtered ceramic thin films, showcased for photocatalytic TiO2.
AB  - Sputter deposited photocatalytic thin films offer high adherence and mechanical
      stability, but typically are outperformed in their photocatalytic properties by
      colloidal TiO2 nanostructures, which in turn typically suffer from problematic
      removal. Here we report on thermally controlled nanocrack formation as a feasible
      and batch applicable approach to enhance the photocatalytic performance of well
      adhering, reactively sputtered TiO2 thin films. Networks of nanoscopic cracks
      were induced into tailored columnar TiO2 thin films by thermal annealing. These
      deep trenches are separating small bundles of TiO2 columns, adding their flanks
      to the overall catalytically active surface area. The variation of thin film
      thickness reveals a critical layer thickness for initial nanocrack network
      formation, which was found to be about 400 nm in case of TiO2. The columnar
      morphology of the as deposited TiO2 layer with weak bonds between respective
      columns and with strong bonds to the substrate is of crucial importance for the
      formation of nanocrack networks. A beneficial effect of nanocracking on the
      photocatalytic performance was experimentally observed. It was correlated by a
      simple geometric model for explaining the positive impact of the crack induced
      enlargement of active surface area on photocatalytic efficiency. The presented
      method of nanocrack network formation is principally not limited to TiO2 and is
      therefore seen as a promising candidate for utilizing increased surface area by
      controlled crack formation in ceramic thin films in general.

PMID- 29176057
TI  - Acoustic-based proton range verification in heterogeneous tissue: simulation
      studies.
AB  - Acoustic-based proton range verification (protoacoustics) is a potential in vivo
      technique for determining the Bragg peak position. Previous measurements and
      simulations have been restricted to homogeneous water tanks. Here, a CT-based
      simulation method is proposed and applied to a liver and prostate case to model
      the effects of tissue heterogeneity on the protoacoustic amplitude and time-of
      flight range verification accuracy. For the liver case, posterior irradiation
      with a single proton pencil beam was simulated for detectors placed on the skin.
      In the prostate case, a transrectal probe measured the protoacoustic pressure
      generated by irradiation with five separate anterior proton beams. After
      calculating the proton beam dose deposition, each CT voxel's material properties
      were mapped based on Hounsfield Unit values, and thermoacoustically-generated
      acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By
      comparing the simulation results for the original liver CT to homogenized
      variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy
      of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2* 
      lower amplitude than simulated in a homogeneous water tank. Protoacoustic
      triangulation of the Bragg peak based on multiple detector measurements resulted
      in 0.4 mm accuracy for a delta-function proton pulse irradiation of the liver.
      For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer
      detectors (<8 cm). For four of the prostate beams, the protoacoustic range
      triangulation was accurate to  ?1.6 mm (delta-function proton pulse). Based on
      the results, application of protoacoustic range verification to heterogeneous
      tissue will result in decreased signal amplitudes relative to homogeneous water
      tank measurements, but accurate range verification is still expected to be
      possible.

PMID- 29176059
TI  - Multi-GPU configuration of 4D intensity modulated radiation therapy inverse
      planning using global optimization.
AB  - We report on the design, implementation and characterization of a multi-graphic
      processing unit (GPU) computational platform for higher-order optimization in
      radiotherapy treatment planning. In collaboration with a commercial vendor
      (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse
      (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon
      processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We
      demonstrate the utility of this platform for large radiotherapy optimization
      problems through the development and characterization of a parallelized particle
      swarm optimization (PSO) four dimensional (4D) intensity modulated radiation
      therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment
      planning system via a vendor-provided scripting interface. Specific challenges
      addressed in this implementation were (i) data management and (ii) non-uniform
      memory access (NUMA). For the former, we alternated between parameters over which
      the computation process was parallelized. For the latter, we reduced the amount
      of data required to be transferred over the NUMA bridge. The datasets examined in
      this study were approximately 300 GB in size, including 4D computed tomography
      images, anatomical structure contours and dose deposition matrices. For
      evaluation, we created a 4D-IMRT treatment plan for one lung cancer patient and
      analyzed computation speed while varying several parameters (number of
      respiratory phases, GPUs, PSO particles, and data matrix sizes). The optimized 4D
      IMRT plan enhanced sparing of organs at risk by an average reduction of [Formula:
      see text] in maximum dose, compared to the clinical optimized IMRT plan, where
      the internal target volume was used. We validated our computation time analyses
      in two additional cases. The computation speed in our implementation did not
      monotonically increase with the number of GPUs. The optimal number of GPUs (five,
      in our study) is directly related to the hardware specifications. The
      optimization process took 35 min using 50 PSO particles, 25 iterations and 5
      GPUs.

PMID- 29176060
TI  - Random dopant fluctuations and statistical variability in n-channel junctionless
      FETs.
AB  - The influence of random dopant fluctuations on the statistical variability of the
      electrical characteristics of n-channel silicon junctionless nanowire transistor
      (JNT) has been studied using three dimensional quantum simulations based on the
      non-equilibrium Green's function (NEGF) formalism. Average randomly distributed
      body doping densities of 2 * 1019, 6 * 1019 and 1 * 1020 cm-3 have been
      considered employing an atomistic model for JNTs with gate lengths of 5, 10 and
      15 nm. We demonstrate that by properly adjusting the doping density in the JNT, a
      near ideal statistical variability and electrical performance can be achieved,
      which can pave the way for the continuation of scaling in silicon CMOS
      technology.

PMID- 29176061
TI  - Exhaled breath temperature in optimally treated asthmatics: severity and
      underlying mechanisms.
AB  - INTRODUCTION: Increased vascularity may lead to loss of heat in the airways and
      may modulate exhaled breath temperature (EBT). Increased EBT has been associated
      with uncontrolled asthma. AIM: We wanted to determine whether the measurement of
      EBT in optimally treated asthmatic patients is influenced by the increased
      vascular permeability and whether Vascular endothelial growth factor (VEGF) is
      implicated in the above process. Furthermore, to assess the impact of asthma
      severity on EBT values. The diagnostic performance of EBT for the identification
      of inflammatory profiles in induced sputum was also assessed. METHODS: 88 stable
      asthmatic patients optimally treated for at least 6 months were studied (46 with
      Severe Refractory Asthma, SRA). EBT was measured with the X-halo device. All
      patients underwent spirometry, sputum induction for the measurement of %
      inflammatory cells and for the assessment of both VEGF and albumin in sputum
      supernatant. The airway vascular permeability index was calculated as the ratio
      of albumin concentrations in induced sputum and serum. RESULTS: EBT ( degrees C)
      was significantly higher in patients with SRA compared to those with mild to
      moderate asthma (median IQR 34.2 [32.4-34.6] versus 31.8 [26.3-34.1], p = 0.001).
      EBT was significantly associated with VEGF levels in sputum supernatant, while
      SRA was recognized as a significant co-variate. No other significant associations
      were observed. Finally, in ROC analysis, the diagnostic performance of EBT for
      the pure eosinophilic or/and neutrophilic profile did not reach statistical
      significance. CONCLUSION: EBT is increasing in severe asthma and is significantly
      modulated by VEGF levels. Despite the above results its performance for
      predicting cellular profiles is of limited value.

PMID- 29176062
TI  - Sol-gel TiO2 colloidal suspensions and nanostructured thin films: structural and
      biological assessments.
AB  - The role of substrate topography in phenotype expression of in vitro cultured
      cells has been widely assessed. However, the production of the nanostructured
      interface via the deposition of sol-gel synthesized nanoparticles (NPs) has not
      yet been fully exploited. This is also evidenced by the limited number of studies
      correlating the morphological, structural and chemical properties of the grown
      thin films with those of the sol-gel 'brick' within the framework of the bottom
      up approach. Our work intends to go beyond this drawback presenting an accurate
      investigation of sol-gel TiO2 NPs shaped as spheres and rods. They have been
      fully characterized by complementary analytical techniques both suspended in
      apolar solvents, by dynamic light scattering (DLS) and nuclear magnetic resonance
      (NMR) and after deposition on substrates (solid state configuration) by
      transmission electron microscopy (TEM) and powder x-ray diffraction (PXRD). In
      the case of suspended anisotropic rods, the experimental DLS data, analyzed by
      the Tirado-Garcia de la Torre model, present the following ranges of dimensions:
      4-5 nm diameter (?) and 11-15 nm length (L). These results are in good agreement
      with that obtained by the two solid state techniques, namely 3.8(9) nm ? and
      13.8(2.5) nm L from TEM and 5.6(1) ? and 13.3(1) nm L from PXRD data. To prove
      the suitability of the supported sol-gel NPs for biological issues, spheres and
      rods have been separately deposited on coverslips. The cell response has been
      ascertained by evaluating the adhesion of the epithelial cell line Madin-Darby
      canine kidney. The cellular analysis showed that titania films promote cell
      adhesion as well clustering organization, which is a distinguishing feature of
      this type of cell line. Thus, the use of nanostructured substrates via sol-gel
      could be considered a good candidate for cell culture with the further advantages
      of likely scalability and interfaceability with many different materials usable
      as supports.

PMID- 29176063
TI  - Silicon surface passivation by PEDOT: PSS functionalized by SnO2 and TiO2
      nanoparticles.
AB  - In this paper, we present a study of silicon surface passivation based on the use
      of spin-coated hybrid composite layers. We investigate both undoped poly(3,4
      ethylenedioxythiophene)/poly-(styrenesulfonate) (PEDOT:PSS), as well as PEDOT:PSS
      functionalized with semiconducting oxide nanomaterials (TiO2 and SnO2). The
      hybrid compound was deposited at room temperature by spin coating-a potentially
      lower cost, lower processing time and higher throughput alternative compared with
      the commonly used vacuum-based techniques. Photoluminescence imaging was used to
      characterize the electronic properties of the Si/PEDOT:PSS interface. Good
      surface passivation was achieved by PEDOT:PSS functionalized by semiconducting
      oxides. We show that control of the concentration of semiconducting oxide
      nanoparticles in the polymer is crucial in determining the passivation
      performance. A charge carrier lifetime of about 275 MUs has been achieved when
      using SnO2 nanoparticles at a concentration of 0.5 wt.% as a filler in the
      composite film. X-ray diffraction (XRD), scanning electron microscopy, high
      resolution transmission electron microscopy (HRTEM), energy dispersive x-ray in
      an SEM, and MU-Raman spectroscopy have been used for the morphological, chemical
      and structural characterization. Finally, a simple model of a photovoltaic device
      based on PEDOT:PSS functionalized with semiconducting oxide nanoparticles has
      been fabricated and electrically characterized.

PMID- 29176064
TI  - Broad-band antireflective pore-like sub-wavelength surface nanostructures on
      sapphire for optical windows.
AB  - Compared with conventional antireflective film, antireflective sub-wavelength
      surface structure provides an ideal choice for sapphire optical window especially
      in harsh environments. However, it is still a challenge to obtain sapphire
      antireflective surface microstructure because of its high hardness and chemical
      inertness. In this paper, combined with optical simulation, we proposed a facile
      method based on the anodic oxidation of aluminum film and following epitaxial
      annealing. Al thin film was deposited on sapphire substrate by magnetron
      sputtering, and anodic oxidation was then performed to prepare surface pore-like
      structures on the Al film. Followed by two-step annealing, both the anodic
      oxidized coating and underlying unoxidized Al film were transformed totally into
      alumina. The parameters of anodic oxidation were analyzed to obtain the optimal
      pore-like structures for the antireflection in the mid-infrared and visible
      spectrum regions, respectively. Finally, the optimized surface sub-wavelength
      nanostructure on sapphire can increase the transmittance by 7% in the wavelength
      range of 3000~5000 nm and can increase 13.2% significantly for visible spectrum
      region, respectively. Meanwhile, the surface wettability can be also manipulated
      effectively. The preparation of surface pore-like sub-wavelength structure by the
      annealing of anodic oxidized aluminum film on sapphire is a feasible, economical
      and convenient approach and can find the applications for various optoelectronic
      fields.

PMID- 29176065
TI  - Vertical MoSe2-MoO x p-n heterojunction and its application in optoelectronics.
AB  - The hybrid n-type 2D transition-metal dichalcogenide (TMD)/p-type oxide van der
      Waals (vdW) heterojunction nanosheets consist of 2D layered MoSe2 (the n-type 2D
      material) and MoO x (the p-type oxide) which are grown on SiO2/Si substrates for
      the first time via chemical vapor deposition technique, displaying the regular
      hexagon structures with the average length dimension of sides of ~8 MUm. Vertical
      MoSe2-MoO x p-n heterojunctions demonstrate obviously current-rectifying
      characteristic, and it can be tuned via gate voltage. What is more, the
      photodetector based on vertical MoSe2-MoO x heterojunctions displays optimal
      photoresponse behavior, generating the responsivity, detectivity, and external
      quantum efficiency to 3.4 A W-1, 0.85 * 108 Jones, and 1665.6%, respectively, at
      V ds = 5 V with the light wavelength of 254 nm under 0.29 mW cm-2. These results
      furnish a building block on investigating the flexible and transparent properties
      of vdW and further optimizing the structure of the devices for better
      optoelectronic and electronic performance.

PMID- 29176066
TI  - Solvent-free nanofluid with three structure models based on the composition of
      MWCNTs/SiO2 core and its adsorption capacity of CO2.
AB  - A series of core/shell nanoparticle organic/inorganic hybrid materials (NOHMs)
      with different weight ratios of two components, consisting of multi-walled carbon
      nanotubes (MWCNTs) and silicon dioxide (SiO2) as the core had been synthesized.
      The NOHMs displays a liquid-like state in the absence of solvent at room
      temperature. Five NOHMs were categorized into three kinds of structure states
      based on different weight ratio of two components in core, named power strip
      model, critical model and collapse model. The capture capacities of these NOHMs
      for CO2 were investigated at 298 K and CO2 pressures ranging from 0 to 5 MPa.
      Compared with NOHM having neat MWCNTs core, it had been revealed that NOHMs with
      power strip model show better adsorption capacity toward CO2, due to its lower
      viscosity and more reactive groups that can react with CO2. In addition, the
      capture capacities of NOHMs with critical model were relatively worse than neat
      MWCNTs-based NOHM. The result is attributed to the aggregation of SiO2 in these
      samples, which may cause the consumption and hindrance of reactive groups.
      However, the capture capacity of NOHM with collapse model was the worst in all
      NOHMs, owing to its lowest content of reactive groups and hollow structure in
      MWCNTs. Besides, it presented non-interference of MWCNTs and SiO2 without
      aggregation state.

PMID- 29176067
TI  - Characterization of a prototype MR-compatible Delta4 QA system in a 1.5 tesla MR
      linac.
AB  - To perform patient plan quality assurance (QA) on a newly installed MR-linac
      (MRL) it is necessary to have an MR-compatible QA device. An MR compatible device
      (MR-Delta4) has been developed together with Scandidos AB (Uppsala, Sweden). The
      basic characteristics of the detector response, such as short-term
      reproducibility, dose linearity, field size dependency, dose rate dependency,
      dose-per-pulse dependency and angular dependency, were investigated for the
      clinical Delta4-PT as well as for the MR compatible version. All tests were
      performed with both devices on a conventional linac and the MR compatible device
      was tested on the MRL as well. No statistically significant differences were
      found in the short-term reproducibility (<0.1%), dose linearity (?0.5%), field
      size dependency (<2.0% for field sizes larger than 5  *  5 cm2), dose rate
      dependency (<1.0%) or angular dependency for any phantom/linac combination. The
      dose-per-pulse dependency (<0.8%) was found to be significantly different between
      the two devices. This difference can be explained by the fact that the diodes in
      the clinical Delta4-PT were irradiated with a much larger dose than the MR-Delta4
      PT ones. The absolute difference between the devices (<0.5%) was found to be
      small, so no clinical impact is expected. For both devices, the results were
      consistent with the characteristics of the Delta4-PT device reported in the
      literature (Bedford et al 2009 Phys. Med. Biol. 54 N167-76; Sadagopan et al 2009
      J. Appl. Clin. Med. Phys. 10 2928). We found that the characteristics of the MR
      compatible Delta4 phantom were found to be comparable to the clinically used one.
      Also, the found characteristics do not differ from the previously reported
      characteristics of the commercially available non-MR compatible Delta4-PT
      phantom. Therefore, the MR compatible Delta4 prototype was found to be safe and
      effective for use in the 1.5 tesla magnetic field of the Elekta MR-linac.

PMID- 29176068
TI  - Role of interbranch pumping on the quantum-statistical behavior of multi-mode
      magnons in ferromagnetic nanowires.
AB  - Theoretical studies are reported for the quantum-statistical properties of
      microwave-driven multi-mode magnon systems as represented by ferromagnetic
      nanowires with a stripe geometry. Effects of both the exchange and the dipole
      dipole interactions, as well as a Zeeman term for an external applied field, are
      included in the magnetic Hamiltonian. The model also contains the time-dependent
      nonlinear effects due to parallel pumping with an electromagnetic field. Using a
      coherent magnon state representation in terms of creation and annihilation
      operators, we investigate the effects of parallel pumping on the temporal
      evolution of various nonclassical properties of the system. A focus is on the
      interbranch mixing produced by the pumping field when there are three or more
      modes. In particular, the occupation magnon number and the multi-mode cross
      correlations between magnon modes are studied. Manipulation of the collapse and
      revival phenomena of the average magnon occupation number and the control of the
      cross correlation between the magnon modes are demonstrated through tuning of the
      parallel pumping field amplitude and appropriate choices for the coherent magnon
      states. The cross correlations are a direct consequence of the interbranch
      pumping effects and do not appear in the corresponding one- or two-mode magnon
      systems.

PMID- 29176069
TI  - PtRu nanoparticles embedded in nitrogen doped carbon with highly stable CO
      tolerance and durability.
AB  - As is well known, the lower durability and sluggish methanol oxidation reaction
      (MOR) of PtRu alloy electrocatalyst blocks the commercialization of direct
      methanol fuel cells (DMFCs). Here, we design a new PtRu electrocatalyst, with
      highly stable CO tolerance and durability, in which the PtRu nanoparticles are
      embedded in nitrogen doped carbon layers derived from carbonization of poly(vinyl
      pyrrolidone). The newly fabricated electrocatalyst exhibits no loss in
      electrochemical surface area (ECSA) and MOR activity after potential cycling from
      0.6-1.0 V versus reversible hydrogen electrode, while commercial CB/PtRu retains
      only 50% of its initial ECSA. Meanwhile, due to the same protective layers, the
      Ru dissolution is decelerated, resulting in stable CO tolerance. Methanol
      oxidation reaction (MOR) testing indicates that the activity of newly fabricated
      electrocatalyst is two times higher than that of commercial CB/PtRu, and the fuel
      cell performance of the embedded PtRu electrocatalyst was comparable to that of
      commercial CB/PtRu. The embedded PtRu electrocatalyst is applicable in real DMFC
      operation. This study offers important and useful information for the design and
      fabrication of durable and CO tolerant electrocatalysts.

PMID- 29176070
TI  - A facile single-step synthesis of polyvinylpyrrolidone-silver nanocomposites
      using a conventional spray dryer.
AB  - We have developed a facile single-step synthesis of silver nanocomposite using a
      conventional spray dryer. We investigated the synthetic conditions by controlling
      the concentrations of the chemical reactants. Further, we confirmed the effect of
      the molecular weight of polyvinylpyrrolidones, and revealed that the molecular
      weight significantly affected the properties of the resultant silver
      nanocomposites. The long-term stability of the silver nanocomposites was tested,
      and little change was observed, even after storage for three months. Most of all,
      the simple commercial implementation, in combination with large-scale synthesis,
      possesses a variety of advantages, compared to conventional complicated and
      costly dry-process synthesis methods. Thus, our method presents opportunities for
      further investigation, for both lab-scale studies and large-scale industrial
      applications.

PMID- 29176071
TI  - Thermodynamics of two-impurity Anderson model with Dzyaloshinskii-Moriya
      interaction.
AB  - In this work, we use the numerical renormalization group (NRG) theory to study
      the thermodynamics of the two-impurity Anderson model. Two different methods are
      used to estimate the effect of Dzyaloshiskii-Moriya (DM) interaction on the
      variation of the Kondo temperature. When the Ruderman-Kittel-Kasuya-Yosida (RKKY)
      interaction is vanishing, the two different estimations give different
      tendencies. If we use the peak of the specific heat to identify the variation of
      the Kondo temperature versus the DM interaction, we get an almost linear
      function. However, if we use the low temperature universal curve of the impurity
      entropy, we get a quadratic function. These results indicate that previous
      debates about the influence of spin-orbit coupling on the Kondo temperature may
      come from the different definitions of the Kondo temperature. When the RKKY
      interaction is ferromagnetic, there are two stages of Kondo screening. Both
      estimations demonstrate that the second stage of the Kondo temperature is
      exponentially dependent on the DM interaction. There results are dramatically
      different from those calculated via perturbation theory.

PMID- 29176072
TI  - Diagnostic reference levels and optimisation in radiology: where do we go from
      here?

PMID- 29176073
TI  - Experience and the results of emergency management of the 1957 accident at the
      Mayak Production Association.
AB  - The experience accumulated while dealing with the aftermath of a major nuclear
      accident (the 'Kyshtym Accident') in 1957 at the Mayak complex in the Southern
      Urals of Russia is summarised. Information is presented on the causes of the
      accident, on the radiation environment and radioactive contamination of the
      affected territory in the critical period, and on the system of emergency
      management and decision-making adopted when dealing with the accident and its
      aftermath. The technical and organisational approaches applied and methods used
      are described, as well as remediation results and the current situation 60 years
      after the accident. It is demonstrated that the implementation of fairly simple
      and self-evident organisational and technical solutions gave good results, and
      that appropriate timely and task-oriented measures were applied. Safety relevant
      conclusions and recommendations are presented.

PMID- 29176074
TI  - Validation and uncertainty analysis of a pre-treatment 2D dose prediction model.
AB  - Independent verification of complex treatment delivery with megavolt photon beam
      radiotherapy (RT) has been effectively used to detect and prevent errors. This
      work presents the validation and uncertainty analysis of a model that predicts 2D
      portal dose images (PDIs) without a patient or phantom in the beam. The
      prediction model is based on an exponential point dose model with separable
      primary and secondary photon fluence components. The model includes a scatter
      kernel, off-axis ratio map, transmission values and penumbra kernels for beam
      delimiting components. These parameters were derived through a model fitting
      procedure supplied with point dose and dose profile measurements of radiation
      fields. The model was validated against a treatment planning system (TPS;
      Eclipse) and radiochromic film measurements for complex clinical scenarios,
      including volumetric modulated arc therapy (VMAT). Confidence limits on fitted
      model parameters were calculated based on simulated measurements. A sensitivity
      analysis was performed to evaluate the effect of the parameter uncertainties on
      the model output. For the maximum uncertainty, the maximum deviating measurement
      sets were propagated through the fitting procedure and the model. The overall
      uncertainty was assessed using all simulated measurements. The validation of the
      prediction model against the TPS and the film showed a good agreement, with on
      average 90.8% and 90.5% of pixels passing a (2%,2 mm) global gamma analysis
      respectively, with a low dose threshold of 10%. The maximum and overall
      uncertainty of the model is dependent on the type of clinical plan used as input.
      The results can be used to study the robustness of the model. A model for
      predicting accurate 2D pre-treatment PDIs in complex RT scenarios can be used
      clinically and its uncertainties can be taken into account.

PMID- 29176075
TI  - Detection of surface-EMG activity from the extensor digitorum brevis muscle in
      healthy children walking.
AB  - OBJECTIVE: The purpose of the study was the assessment of activation patterns of
      the extensor digitorum brevis (EDB) muscle in healthy children, during walking at
      self-selected speed and cadence. APPROACH: To this end, statistical gait analysis
      was performed on surface electromyographic (sEMG) signals of the EDB, in a large
      number (hundreds) of strides per subject. sEMG data from the tibialis anterior
      (TA) and gastrocnemius lateralis (GL) were also investigated for comparative
      purposes. MAIN RESULTS: Results from 23 healthy children showed a large
      variability in the number of muscle activations, occurrence frequency, and onset
      offset instants across considered strides. The assessment of different modalities
      of muscle activation allowed the identification of a single activity pattern,
      common to all the modalities and we were able to characterize the behavior of the
      EDB during the gait of healthy children. The pattern of EDB activity centered in
      two main regions of the gait cycle: in the second half of the stance phase
      (detected in 100% of subjects) and in the final swing phase (50%). Comparison
      with the TA and GL regions of activity suggested that the EDB and TA worked
      mainly as antagonist muscles for the ankle joint, while the EDB and GL did not
      oppose each other in action, but acted in synergy for the control of the ankle
      joint during walking. SIGNIFICANCE: The 'Normality' pattern for the EDB activity
      reported here represents the first attempt to develop a reference for dynamic
      sEMG of the EDB in healthy children, enabling us to include the physiological
      variability of the phenomenon. Present results could be useful for discriminating
      physiological and pathological behavior in children and for deepening the
      maturation of the gait.

PMID- 29176076
TI  - Electrocatalytic CO2 reduction near the theoretical potential in water using Ru
      complex supported on carbon nanotubes.
AB  - We successfully developed a highly efficient electrode for CO2 reduction using a
      Ru-complex catalyst ([Ru]) supported on carbon paper coated with multi-walled
      carbon nanotubes (CPCNT/[Ru]). The CPCNT/[Ru] electrode promoted the CO2
      reduction reaction in aqueous solution near the theoretical potential, and
      produced formate linearly with a current density of greater than 0.9 mA cm-2 at 
      0.15 V (versus RHE) for at least 24 h. Due to the outstandingly low
      overpotential, a monolithic tablet-shaped photo-device was realized by coupling
      the CPCNT/[Ru] catalyst with amorphous SiGe-jn as a light absorber and IrO x as a
      water oxidation catalyst, and the device produced formate from CO2 and water in a
      single-compartment reactor. The nanotubes enhanced the rate for CO2 reduction at
      [Ru], and accordingly a solar-to-chemical conversion efficiency of 4.3% for
      formate production was achieved when the CO2 reduction and H2O oxidation sites
      had the same area.

PMID- 29176077
TI  - Erythrocyte membrane-coated Gold nanocages for targeted cancer photothermal and
      chemical therapy.
AB  - Recently, RBC membrane coated nanoparticles have attracted much attention because
      of their excellent immune escape ability; meanwhile, Au nanocages (AuNs) have
      been extensively used for cancer therapy due to its photothermal effect and drug
      delivery capability. The combination of RBC membrane coating and Au nanocages may
      provide an effective approach for targeted cancer therapy. However, few reports
      have shown the utilization of combining these two technologies. Here, we present
      the development of Erythrocyte membrane-coated Gold nanocages for targeted cancer
      photothermal and chemical therapy. First, anti-EpCam antibodies are used to
      modify RBC membranes to target 4T1 cancer cells. Second, the antitumor drug
      paclitaxel is encapsulated into AuNs. Then, the AuNs are coated with the modified
      RBC membranes. This new nanoparticles are termed EpCam-RPAuNs. We characterize
      the capability of EpCam-RPAuNs for selective tumor targeting via exposure to the
      near-infrared irradiation. Experimental results demonstrate that EpCam-RPAuNs can
      effectively generate hyperthermia and precisely deliver the antitumor drug PTX to
      targeted cells. We also validate the biocompatibility of our EpCam-RPAuNs in
      vitro. By combining the targeting moleculars modified RBC membrane and AuNs, our
      approach provides a new way to design biomimetic nanoparticles to enhance the
      surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be
      potentially applied for cancer diagnoses and therapies.

PMID- 29176078
TI  - One stage surgery for synchronous liver metastasis from a neuroendocrine tumor of
      the colon. A case report.
AB  - INTRODUCTION: Neuroendocrine tumors (NETs) are a heterogeneous group of tumors.
      NET of colon represent less than 1% of colonic tumors. Synchronous liver
      metastases, present in 75-80%, are considered significant adverse prognostic
      indicators. Liver is the second commonest site for metastasis in patients with
      colorectal neuroendocrine tumors. Available treatment options include surgical
      resection, chemotherapy, biotherapy. Surgery is the gold standard for curative
      therapy and it is strictly related to the localization, the grade of tumor, and
      the stage of disease. CASE REPORT: We present a 64-year-old man with clinical
      carcinoid syndrome. Colonoscopy revealed ileocecal valve vegetating mass with
      negative biopsy. CT scans of thorax and abdomen showed a voluminous lesion (10 cm
      of diameter) of right liver. CEA, CA 19.9 and aFP were all normal. Only urinary
      5HIAASerum 5-hydroxyindoleactic acid and blood Chromogranin A were positive.
      Surgical strategy was to treat the primary tumor and the liver synchronous
      metastasis in one stage surgery. DISCUSSION: Management of NETs liver metastases
      is challenging and requires aggressive therapy. Currently, there are many
      therapeutic options for metastatic NETs. Although complete surgical resection
      remains the optimal therapy and aggressive surgical resection increases the 5
      year survival of NETs with solitary liver metastasis to 100%. In this case,
      clinical status with doubt of carcinoid syndrome was essential for diagnosis and
      for subsequent surgical strategy with one stage surgery. CONCLUSION: Resection of
      the primary tumor, liver metastases, and local mesenteric lymph node metastases
      is thought to strictly promote long-term survival and quality of life. Typically,
      a multidisciplinary approach is a cornerstone for decision making while dealing
      with this aggressive disease. KEY WORDS: Carcinoid syndrome, Liver surgery, NETs,
      Neuroendocrine tumor, One stage surgery, Synchronous liver metastasis.

PMID- 29176079
TI  - If the Framingham Heart Study Did Not Invent the Risk Factor, Who Did?
AB  - Most historians, epidemiologists, and physicians credit the Framing-ham Heart
      Study for introducing the term "risk factor" to public health and medicine. Many
      add that the term came from life insurance companies. This familiar history is
      incorrect. Taking advantage of the expanding availability of digitized and full
      text searchable journals, textbooks, newspapers, and other sources, we have
      uncovered a deeper and broader history. Antecedent concepts (such as risk,
      factor, predisposition) have ancient roots. "Risk factor" began to appear in the
      late 19th and early 20th centuries in many industries, not just in insurance but
      also in finance, agriculture, and manufacturing. The term appeared in the
      occupational health literature in 1922. It reappeared in the 1950s in many
      different areas of medicine including psychiatry, surgery, cardiology,
      epidemiology, and aerospace medicine. Furthermore, despite the influential
      appearance of "risk factor" in a 1961 Framingham Heart Study publication, the
      term did not gain momentum in medicine and public health until the mid-1970s.
      While our analysis is not exhaustive, our findings are extensive enough to
      require a substantial revision to the history of the risk factor.

PMID- 29176080
TI  - The Etiological Stance: Explaining Illness Occurrence.
AB  - Kelly, Kelly, and Russo (2014) recently proposed to integrate biological,
      behavioral, and social mechanisms into "mixed mechanisms" situated in the
      individual's "lifeworld" when considering illness causation. This article
      suggests considering terminological discrepancies, replacing the pathogenetic
      with an etiological perspective (that includes, but is not limited to
      pathogenesis), and rethinking whether the lifeworld concept adds to what we
      consider an individual's "environment." It also proposes replacing the notion of
      "mixed mechanisms" with the concept of "combined contributions" of factors in
      etiological explanations of illness.

PMID- 29176081
TI  - Biocontaining: Purification, Restoration, and Meaning-Making.
AB  - Biocontaining during the recent Ebola outbreak served to affirm the social
      significance of biomedicine, even though it had little measurable effect on the
      pandemic itself. Taking up key insights of Mary Douglas and Victor Turner
      concerning the essential meaning-making tasks of culture, this article discusses
      how biocontaining as an activity contributed to the work of social reassurance
      and meaning-making in U.S. and global society during the crisis. The analysis is
      based in significant part on fieldwork done at the Nebraska Biocontainment Unit
      (NBU), study of NBU educational materials, and follow-up conversations with
      personnel staffing that unit.

PMID- 29176082
TI  - The Best Interest Standard: Same Name but Different Roles in Pediatric Bioethics
      and Child Rights Frameworks.
AB  - This article explores the intersection of pediatric bioethics and child rights by
      examining the best interest standard as it operates within the pediatric
      bioethics framework in the United States and the child rights framework based on
      the UN 1989 Convention on the Rights of the Child (CRC). While the "best interest
      of the child" standard is central to both pediatric bioethics and the child
      rights community, it operates only as a guidance principle, and not as an
      intervention principle, in decision-making within U.S. pediatric bioethics,
      whereas it operates as both a guidance and intervention principle in the child
      rights community. The differences in how the best interest standard is
      operationalized lead to different roles for the family, the state, and the minor
      in decision-making processes and outcomes. We examine the recent case of Charlie
      Gard to illustrate some of these differences.

PMID- 29176083
TI  - Marston Bates, Visionary Environmentalist.
AB  - Marston Bates (1906-1974) raised questions concerning man's relationship to
      nature, questions that are of much greater importance today than they were during
      his lifetime. He began his career with the Rockefeller Foundation as a mosquito
      expert, and by 1955 he had established himself as one of the key players in the
      field of human ecology through a series of publications that brought together in
      a clear and readable style the complexities involved in understanding human
      ecology. This article traces Bates's development and discusses how the Foundation
      failed to engage the subject of human ecology, even at a time when it recognized
      its critical importance to humankind.

PMID- 29176084
TI  - A Child's Right to Be Well Born: Venereal Disease and the Eugenic Marriage Laws,
      1913-1935.
AB  - An extensive literature describes the legal impact of America's eugenics
      movement, and the laws mandating sterilization, restriction of marriage by race,
      and ethnic bans on immigration. But little scholarship focuses on the laws
      adopted in more than 40 states that were commonly referred to as "eugenic
      marriage laws." Those laws conditioned marriage licenses on medical examinations
      and were designed to save innocent women from lives of misery, prevent stillbirth
      or premature death in children, and save future generations from the myriad
      afflictions that accompanied "venereal infection." Medical journals, legal
      journals, and every kind of public press outlet explained the "eugenic marriage
      laws" and the controversies they spawned. They were inextricably bound up in
      reform movements that attempted to eradicate prostitution, stamp out STIs, and
      reform America's sexual mores in the first third of the 20th century. This
      article will explain the pedigree of the eugenic marriage laws, highlight the
      trajectory of Wisconsin's 1913 eugenic enactment, and explore how the Wisconsin
      Supreme Court case upholding the law paved the way for the majority of states to
      regulate marriage on eugenic grounds.

PMID- 29176085
TI  - Maintaining Compassion for the Suffering Terminal Patient While Preserving Life:
      An Orthodox Jewish Approach.
AB  - Regardless of one's religious beliefs, the process of making end-of-life
      decisions is inherently difficult and emotionally trying. The caregiver, family
      member, or friend is faced with making heart-wrenching decisions for loved ones
      where the line between support and cruelty may feel blurred. By evaluating the
      process by which traditional Judaism harmonizes the apparently conflicting
      obligations of the caregiver in end-of-life scenarios through three practical
      cases, all people can gain insight into managing this delicate balancing act and
      may develop generalizable approaches that recognize and appreciate the
      particularities of each patient's needs. The traditional Orthodox Jewish approach
      to terminal illness is guided by defined legal principles that facilitate greater
      understanding and promote more empathetic care for Jewish patients.

PMID- 29176086
TI  - Choosing to Care for Children Who Might Die: Conversations with Pediatric
      Residents.
AB  - This essay evolved from observations that pediatric resident physicians'
      experiences with patient deaths might influence their career paths after
      completing residency training. The author's journey as a physician led her to
      wonder whether young pediatricians who gravitated toward careers in primary care
      had qualitatively different experiences with death and dying during their medical
      training compared to those who chose fields in which they were more likely to
      confront death and dying on a regular basis, such as pediatric critical care,
      neonatology, or pediatric oncology. Ten pediatric residents agreed to participate
      in conversations that were then expanded to encompass related concepts of
      "devastating diagnoses" and of "giving bad news." Three central themes-the
      privilege of supporting families through difficult times, the challenge of
      navigating between expectations and uncertainty, and the resilience of children
      experiencing illness-emerged as having profoundly influenced pediatricians'
      understanding of their professional journeys and identities.

PMID- 29176087
TI  - In Pursuit of Educational Integrity: Professional Identity Formation in the
      Harvard Medical School Cambridge Integrated Clerkship.
AB  - Graduates of Harvard Medical School's Cambridge Integrated Clerkship (CIC)
      describe several core processes that may underlie professional identity formation
      (PIF): encouragement to integrate pre-professional and professional identities;
      support for learner autonomy in discovering meaningful roles and
      responsibilities; learning through caring relationships; and a curriculum and an
      institutional culture that make values explicit. The authors suggest that the
      benefits of educational integrity accrue when idealistic learners inhabit an
      educational model that aligns with their own core values, and when professional
      development occurs in the context of an institutional home that upholds these
      values. Medical educators should clarify and animate principles within curricula
      and learning environments explicitly in order to support the professional
      identity formation of their learners.

PMID- 29176088
TI  - Hope and Resentment.
AB  - A common challenge for both health-care providers and policymakers is to deal
      with people as people, rather than merely as biological or social problems to be
      managed. In terms introduced in P. F. Strawson's much-discussed essay "Freedom
      and Resentment" (1962), the difficulty is to maintain a reactive "participant
      stance," rather than a solely objective perspective, toward those with whom they
      have difficulties. Vaccine resistance and refusal provides a particularly pointed
      instance of this challenge: there is evidence that suggests standard methods of
      rational persuasion tend to be ineffective, even counter-productive, in easing
      skepticism about the safety, effectiveness, or appropriateness of vaccines and
      vaccine regimens. If clear and vivid information about relative risks is not
      compelling, the temptation to manipulate rather than convince skeptics may be
      hard, or even seem wrong, to resist. Mark Navin's recent Values and Vaccine
      Refusal (2016) can be read as a reminder of the importance-and the difficulty-of
      maintaining a participant stance toward vaccine deniers or resisters.

PMID- 29176089
TI  - The Body Politic in Pain.
AB  - In his 2015 book Pain: A Political History, Keith Wailoo demonstrates how a
      medicalized condition became central to defining party politics in the United
      States from World War II down to the present. Drawing on sources ranging from
      postwar Congressional hearings concerning the veteran welfare state to debates
      surrounding Rush Limbaugh's OxyContin addiction, Wailoo offers a fresh analysis
      of both U.S. political history and medical history, showing how today's highly
      polarized party system emerged in part from debates surrounding the existence and
      worth of pain, as well as its management.

PMID- 29176090
TI  - Small is Beautiful, but Universals are Equitable.

PMID- 29176091
TI  - A Dedicated Hostel-based Liver Service for Vulnerable/Homeless Adults: Response
      to: Needs Assessment of HCV-Infected Individuals Experiencing Homelessness and
      Implications.

PMID- 29176092
TI  - Regional Variations in the Interpretation of the End-Stage Renal Disease Thirty
      Month Coordination Period: Potential Implications for Patient Care.
AB  - Chronic kidney disease is a non-communicable disease that is now well recognized
      as a major source of premature morbidity and mortality. In general, racial/ethnic
      minorities in the United States are more likely than non-minority groups to
      develop end-stage renal disease (ESRD), but paradoxically most have a lower
      mortality risk. Unlike most minorities, dialysis patients in Puerto Rico have a
      mortality risk nearly 50% higher than the national average. Multiple factors such
      as medical conditions, socioeconomic, environmental, and health system factors
      can influence health outcomes for patients with ESRD. We describe one potential
      health system factor that may contribute to this finding, a unique interpretation
      and implementation of the ESRD Medicare Secondary Payer provision in the
      Commonwealth of Puerto Rico. We conducted a search of regulatory documents and
      key stakeholder interviews to help envision the potential implications of these
      differences for dialysis facilities, health care providers, and patients with
      ESRD.

PMID- 29176093
TI  - Evaluating the Impact of the Affordable Care Act on HIV Care, Outcomes,
      Prevention, and Disparities: A Critical Research Agenda.
AB  - In the United States (U.S.), health care policy plays a critical role in ensuring
      adequate care for people living with HIV (PLWH), eliminating new HIV infections,
      and reducing health disparities. The 2010 Patient Protection and Affordable Care
      Act (ACA) was designed to make health care more accessible, of higher quality,
      and more affordable. Many provisions of the ACA are considered relevant to HIV
      care and prevention. Because PLWH have unique care needs and many groups at risk
      for infection are members of vulnerable populations, timely and comprehensive
      evaluation of the ACA in terms of HIV is critical. In this paper, we discuss
      components of the ACA relevant to HIV care and prevention, describe their
      anticipated and initial effects, and finally, outline a research agenda to inform
      future HIV programming and policy.

PMID- 29176094
TI  - Providing Specialty Care for the Poor and Underserved at Student-Run Free Clinics
      in the San Francisco Bay Area.
AB  - This report describes the model of specialty clinics implemented at Stanford
      University's two student-run free clinics, Arbor Free Clinic and Pacific Free
      Clinic, in the San Francisco Bay Area. We describe our patient demographic
      characteristics and the specialty services provided. We discuss challenges in
      implementing specialty care at student-run free clinics.

PMID- 29176095
TI  - Assessing Health Care Access and Use among Indigenous Peoples in Alberta: a
      Systematic Review.
AB  - Alberta's Indigenous population is growing, yet health care access may be
      limited. This paper presents a comprehensive review on health care access among
      Indigenous populations in Alberta with a focus on the health care services use
      and barriers to health care access. Scientific databases (PubMed, EMBASE, CINAHL,
      and PsycINFO) and online search engines were systematically searched for studies
      and grey literature published in English between 2000 and 2013 examining health
      care services access, use and barriers to access among Indigenous populations in
      Alberta. Information on health care services use and barriers to use or access
      was synthesized based on the MOOSE guidelines. Overall, compared to non
      Indigenous populations, health care use rates for hospital/emergency room
      services were higher and health care services use of outpatient specialists was
      lower among Indigenous peoples. Inadequate numbers of Indigenous health care
      professionals; a lack of cross-cultural training; fear of foreign environments;
      and distance from family and friends were barriers to health care use and access.
      Inequity in social determinants of health among Indigenous peoples and inadequate
      "health services with prevention approaches," may contribute to present health
      disparities between Indigenous and non-Indigenous populations in the province.

PMID- 29176096
TI  - Short Sleep Duration is Associated with Obesity in Hispanic Manufacturing
      Workers.
AB  - The present study examined the relationship between obesity and sleep duration
      among Hispanic manufacturing workers. Two hundred and twenty eight Hispanic
      workers from eight manufacturing plants completed an in-person interview that
      included measures of demographics, health literacy, and sleep duration. Height
      and weight were directly assessed. A logistic regression, controlling for gender,
      education, age, income, physical activity levels, self-reported health status,
      and health literacy, indicated that workers who slept six hours or less were
      significantly more likely to be obese than those sleeping seven to nine hours
      (OR: 1.90, 95% CI: 1.04-3.47). Our results extend previous research on the
      association between sleep duration and obesity to an understudied population of
      Hispanic workers.

PMID- 29176097
TI  - Access to Health Care among Mexican Migrants and Immigrants: A Comparison across
      Migration Phases.
AB  - OBJECTIVES: We examined differences in, and factors associated with, access to
      health services among Mexican im/migrants to the U.S. across migration phases,
      including pre-departure, destination, interception, and return. METHODS: Using
      data from a cross-sectional survey conducted in Tijuana, Mexico (N = 1,541), we
      computed descriptive statistics and staged logistic regressions to estimate
      health care access indicators and factors associated with access to services.
      RESULTS: Im/migrants at post-migration phases had lower likelihood of receiving
      health care and having a usual source of care, and higher rates of forgone care,
      than their counterparts at pre-departure. These differences were partly explained
      by length of migration phase, health insurance status, transportation barriers,
      and detention or imprisonment. CONCLUSIONS: Mexican im/migrants face challenges
      in accessing health services across the migration continuum, especially at post
      migration phases. Binational efforts to provide affordable insurance coverage and
      reduce transportation limitations and incarceration could contribute to improving
      health care access among Mexican im/migrants.

PMID- 29176098
TI  - Incidence of Non-Melanoma Skin Cancer in the Uninsured.
AB  - Non-melanoma skin cancer (NMSC) is a common reason for outpatient primary care
      visits. Uninsured patients may be at a higher risk for NMSC due to lack of access
      to health care and a possible increased risk of sun exposure due to insecure
      housing. The true incidence of NMSC in this population is unknown. In order to
      determine the population's incidence of NMSC we performed a retrospective chart
      review on all patients (n = 656) seen at the Lubbock Impact Free Clinic from July
      1, 2014 through July 30, 2015. This highlighted an increased incidence of NMSC in
      our uninsured population (1.4% [9/656]), particularly in the 50-64 age range
      (2.8% [7/250]) when compared with the general United States population (0.65%
      1.05%). We believe that skin care education and routine skin cancer screening
      should be emphasized in the care of these patients due to their increased risk.

PMID- 29176099
TI  - Real-world Outcomes of Hepatitis C Treatment during the Interferon-free Era at an
      Urban Safety-net Hospital.
AB  - BACKGROUND: Little is known about real-world outcomes for new interferon-free
      treatment for hepatitis C virus (HCV) among underserved and diverse communities.
      OBJECTIVE: To identify predictors of treatment prescription and evaluate outcomes
      as measured by sustained virologic response (SVR) with HCV RNA testing three
      months after therapy completion. DESIGN: Retrospective cohort at a safety-net
      health care system. PARTICIPANTS: Patients with (1) at least one clinical visit
      between December 6, 2013, and December 31st 2014; and (2) at least three months
      follow-up. KEY RESULTS: Predominantly non-White cohort (61%). Of 1,284 HCV
      infected patients 121 prescribed sofosbuvir-based therapy. Severe liver fibrosis
      (OR 1.66, 95% CI 1.05, 2.64) independently associated with treatment
      prescription. In those with evaluable HCV RNA, SVR was 99%. CONCLUSION: Cure
      rates similar to clinical trial data can be achieved in diverse underserved
      communities.

PMID- 29176100
TI  - Utilization and Cost Analysis of a Chronically Ill, Newly Insured Indigent
      Population.
AB  - The Affordable Care Act expanded health insurance for low-income, uninsured
      individuals. Few longitudinal analyses have investigated how insurance expansion
      influences cost and utilization among adults with chronic conditions. This study
      conducted longitudinal analysis investigating time trends in utilization and cost
      among newly insured, chronically ill, low-income individuals using Generalized
      Estimating Equations models. For hospitalization, hospital outpatient services,
      emergency department (ED) visits, and primary care visits, two indicators were
      measured: the proportion of enrollees with services and the average number of
      visits among users. The average health expenditure per person was estimated using
      a gamma distribution. Results indicate that the number of individuals using
      inpatient or ED services was highest during the first six months following
      insurance coverage and decreased in subsequent periods, while primary care visits
      increased during the first year. Using six-month rather than annual measures of
      utilization and cost may be necessary to identify short-run changes following
      initial insurance coverage.

PMID- 29176101
TI  - Indian Health Service Coverage among American Indians and Alaska Natives in
      Federal Tribal Areas.
AB  - Compared with other racial/ethnic groups, American Indians and Alaska Natives
      (AIANs) have higher uninsured rates and worse health outcomes. Using data from
      the 2010-2014 American Community Survey, we employ logistic regression techniques
      to assess the characteristics associated with Indian Health Service (IHS)
      coverage among working-age AIANs who have health insurance or are uninsured.
      Across all insurance categories, geographic residence is a factor in IHS
      coverage. Among the uninsured, those with and without IHS coverage are more
      dissimilar than similar across socioeconomic characteristics. When controlling
      for confounding characteristics, people who are uninsured or have Medicaid have a
      much higher IHS coverage rate compared with those with employer-sponsored
      insurance. This indicates IHS coverage is an important component for the
      uninsured and it complements Medicaid services. This work identifies a need for
      increased outreach to eligible AIANs about IHS programs, particularly those
      without comprehensive care.

PMID- 29176102
TI  - Quality Health Care for Homeless Children: Achieving the AAP Recommendations for
      Care of Homeless Children and Youth.
AB  - BACKGROUND: We assessed whether and how health care organizations serving
      homeless pediatric patients meet recommendations issued by the American Academy
      of Pediatrics (AAP). METHODS: We conducted a web-based survey of Health Care for
      the Homeless (HCH) Program grantees serving children. RESULTS: Of 169 grantees,
      77 (46%) responded. All organizations reported connecting patients to specialty
      services. Nearly all reported screening for homelessness (90%), facilitating
      Medicaid enrollment (90%), connecting patients to benefits (94%), addressing
      underlying causes of homelessness (83%), assisting with transportation (83%), and
      knowing about the causes of homelessness (76%). Fewer reported integrating
      comprehensive care into acute visits (61%) or having medical-legal partnerships
      (57%). Federally qualified health center status was associated with meeting more
      recommendations. We described barriers and facilitators to meeting
      recommendations. DISCUSSION: Health care organizations serving homeless children
      largely meet AAP recommendations, but integrating comprehensive care into acute
      visits remains an area for improvement. Disseminating best practices may support
      guideline adherence.

PMID- 29176103
TI  - Neonatal Abstinence Syndrome in East Tennessee: Characteristics and Risk Factors
      among Mothers and Infants in One Area of Appalachia.
AB  - OBJECTIVE: To describe the epidemiology of neonatal abstinence syndrome (NAS) in
      a 16-county Appalachian area of eastern Tennessee. METHODS: The Tennessee
      Surveillance System for NAS provided data on maternal sources of opioids. Data
      linking hospital discharge diagnosis for NAS to birth certificate data allowed us
      to compare maternal, delivery, and infant characteristics for NAS births with
      those for non-NAS births. RESULTS: There were 339 cases of NAS in 2013 and 367 in
      2014, for NAS rates of 25.5 and 28.5 per 1,000 live births, respectively. When
      compared with the state overall, mothers of NAS infants in eastern Tennessee were
      more likely to use opioids that had been prescribed to another person. There were
      numerous maternal, infant, and delivery characteristics that were significantly
      different for NAS births compared with non-NAS births. CONCLUSION: Neonatal
      abstinence syndrome is epidemic in the eastern Tennessee area of Appalachia, with
      unique maternal and infant characteristics that have important implications for
      primary, secondary, and tertiary prevention.

PMID- 29176104
TI  - Characteristics of Medical Students Planning to Work in Medically Underserved
      Settings.
AB  - We explored medical students' desire to practice medicine in a medically under
      served area (MUS). We surveyed M1-M4 students at Loyola University Stritch School
      of Medicine (66% overall response rate). Primary outcome was intent to locate
      future practice in a MUS. Predictor variables included gender, race/ethnicity,
      and measures of religiosity, spirituality, sense of calling, burnout, and
      interest in primary care. In bivariate analysis, we found statistically
      significant associations between our primary outcome variable and gender,
      spirituality, growing up in MUS, sense of calling, primary care interest, and
      burnout. All associations except burnout persisted in multivariate analysis. As
      in studies of physicians, medical student intent to practice in MUS correlated
      with gender, growing up in MUS, and interest in primary care. Intent correlated
      with sense of calling and spirituality but not religiosity or burnout. Future
      research is warranted as spirituality and sense of calling may play a role in
      career decisions.

PMID- 29176105
TI  - Frailty Assessment in Patients Utilizing a Free Clinic.
AB  - PURPOSE: Frailty is most commonly associated with older adults; however, it has
      also been identified in vulnerable populations, including homeless adults.
      Patients who seek health care services in a free clinic often report physical
      exhaustion, difficulty coping with stressors, chronic disease states,
      environmental limitations, and a lack of social support, which may contribute to
      a state of frailty. This pilot study (N = 38) was conducted in adults ages 40-64
      years who utilized a free clinic to determine if factors suggestive of frailty
      were present. METHODS: The Comprehensive Frailty Assessment Instrument (CFAI) was
      the primary data collection instrument. Anthropometrics and physical performance
      data were also collected. RESULTS: Physical indicators of frailty were present in
      60% of the sample. Psychological, social, and environmental factors affecting
      health were identified. Sixty-three percent of the participants scored frail or
      very frail on the CFAI. A larger study is needed to confirm these findings.

PMID- 29176106
TI  - The Rikers Island Hot Spotters: Exploring the Needs of the Most Frequently
      Incarcerated.
AB  - A cohort of frequently incarcerated individuals in the New York City jail system
      was identified through "hot spotting" analysis. This group demonstrated higher
      levels of substance use, mental illness, and homelessness than the general jail
      population, and was typically incarcerated on minor criminal charges. To
      understand this population better, in-depth interviews (n = 20) were conducted at
      three Rikers Island correctional facilities with people who had entered the jail
      system at least 18 times in a six-year period. Findings showed that life
      circumstances, chronic homelessness, mental illness, and substance use resulted
      in repeated institutionalization across multiple settings. Participants described
      an "institutional circuit" that promoted a state of permanent instability
      characterized by rotating involvement with custodial institutions. Exiting the
      institutional circuit requires the ability to navigate complex bureaucratic
      systems; however, without structural reorganization in social service delivery
      and an emphasis on permanent housing, participants in this group are unlikely to
      break the cycle.

PMID- 29176107
TI  - Maternal Health Care Use by Pregnant Women Living with HIV: Factors Associated
      with Prenatal, Delivery, and Postnatal Care in Haiti.
AB  - This study compares maternal health care utilization of women living with HIV
      with that of their HIV-negative peers in Haiti. Data from the 2012-2013 Haiti
      Demographic and Health Survey were analyzed. Three percent of mothers were HIV
      positive. These mothers had over two times greater odds than HIV-negative mothers
      of accessing prenatal care in the first trimester and to deliver in a medical
      institution, and 1.9 greater odds of having a medical personnel at delivery.
      Haiti has made progress in increasing maternal health care utilization,
      specifically in an effort to reduce mother-to-child-transmission of HIV. Haiti's
      ability to bring institutions together, implement practical policies, and
      actively engage the most vulnerable pregnant women, those with HIV and those
      residing in remote areas, may offer valuable insight to similar resource-poor
      nations seeking to reduce rates of mother-to-child transmission.

PMID- 29176108
TI  - Oral Health Status of Institutionalized Older Women from Different Socioeconomic
      Positions.
AB  - OBJECTIVE: To determine the association between oral health and socioeconomic
      position in institutionalized older women in Mexico City. METHODS: A cross
      sectional study was performed in two groups: high socioeconomic position (HSEP),
      living in a private retirement home, and low socioeconomic position (LSEP),
      living in a public assistance center. Oral health was determined by edentulism,
      oral hygiene, healthy teeth, experience of dental caries, missing and filled
      teeth, gingival bleeding, dental calculus, and periodontal disease. A latent
      class analysis (LCA) was used to classify oral health status in dentate. RESULTS:
      Included were 170 women (HSEP 54.1% and LSEP 45.8%), average age 77.3 (SD = 9.3)
      years. Oral health status was formed: Edentulous 32.4% HSEP and 67.6% LSEP; Class
      1 Unfavorable 0% HSEP and 100% LSEP; Class2 Slightly favorable 41.2% HSEP
      and58.8% LSEP; and Class3 Favorable 84.6% HSEP and 15.4% LSEP. There was a
      statistically significant association between socioeconomic position (p < .001)
      and oral health status. CONCLUSIONS: The oral health of women studied was not
      optimal. Higher socioeconomic position was associated with better oral health
      status.

PMID- 29176109
TI  - Routine Screening for Pregnancy Intention to Address Unmet Reproductive Health
      Needs in Two Urban Federally Qualified Health Centers.
AB  - OBJECTIVE: The goal of this project was to increase rates of screening for
      pregnancy intention in primary care. METHODS: Two urban federally qualified
      health centers with diverse patient populations undertook a quality improvement
      project to increase rates of routine screening for pregnancy intention among pre
      menopausal non-pregnant women ages 12-45 without history of sterilization.
      Responses were recorded in the electronic medical record (EMR). RESULTS:
      Screening rates of eligible women increased from 0% to 68.3% and from 49.0% to
      80.3% at Sites 1 and 2, respectively. Adolescents were screened at lower rates
      than adults (p < .0001). There was no significant difference in screening rates
      between English and non-English speaking patients. Project challenges included
      cultural relevance to certain patient groups, staff turnover, and time for follow
      up counseling. CONCLUSIONS: Implementation of routine pregnancy intention
      screening is important to address unmet reproductive health needs, and can be
      successfully implemented through an EMR regardless of primary language.

PMID- 29176110
TI  - Enhancing Administrative Data to Predict Emergency Department Utilization: The
      Role of Neighborhood Sociodemographics.
AB  - Much of emergency department use is avoidable, and high-quality primary care can
      reduce it, but performance measures related to ED use may be inadequately risk
      adjusted. To explore associations between emergency department (ED) use and
      neighborhood poverty, we conducted a secondary analysis of Massachusetts managed
      care network data, 2009-2011. For enrollees with commercial insurance (n =
      64,623), we predicted any, total, and total primary-care-sensitive (PCS) ED
      visits using claims/enrollment (age, sex, race, morbidity, prior ED use), network
      (payor, primary care provider [PCP] type and quality), and census-tract-level
      characteristics. Overall, 14.6% had any visit; mean visits per 100 persons were
      18.8 (+/-0.2) total and 7.6 (+/-0.1) PCS. Neighborhood poverty predicted all
      three outcomes (all P< .001). Holding providers accountable for their patients'
      ED use should avoid penalizing PCPs who care for poor and otherwise vulnerable
      populations. Expected use targets should account for neighborhood-level variables
      such as income, as well as other risk factors.

PMID- 29176111
TI  - Dialysis Hospitalization Inequities by Hispanic Ethnicity and Immigration Status.
AB  - Medicare provides access to chronic outpatient dialysis for most U.S. patients
      diagnosed with end-stage renal disease. However, many new and/or undocumented
      immigrants do not qualify due to lawful presence and work credit requirements.
      Medicare-ineligible dialysis patients often wait until their health is poor
      enough for admission to emergency room dialysis. We use University of New Mexico
      Hospital chart data from 2013-2016 for a case-control study measuring the
      likelihood of being admitted to an emergency room for dialysis among patients who
      use interpreters, which is employed as a proxy for new and undocumented
      immigrants, compared with other patients. We find Hispanic patients who use an
      interpreter are significantly more likely to be admitted to emergency rooms for
      dialysis compared with patients who did not use an interpreter. This study
      highlights the need for national, state, and local policies to address this
      inefficient and inequitable healthcare pattern resulting in unnecessary costs and
      suffering.

PMID- 29176112
TI  - Access to Digital Communication Technology and Perceptions of Telemedicine for
      Patient Education among American Indian Patients with Diabetes.
AB  - INTRODUCTION: Health care access for medically underserved patients managing
      chronic conditions is challenging. While telemedicine can support patient
      education and engagement, the "digital divide" may be particularly problematic
      among the medically underserved. This study evaluated physical access to digital
      devices, use of e-mail and social media tools, and perceptions of telemedicine
      among American Indian (AI) patients with diabetes mellitus (DM). METHODS: Survey
      data were collected from AI patients with DM during teleophthalmology exams.
      RESULTS: Eighty-eight percent of patients had access to digital device(s), 70%
      used e-mail, and 56% used social media. Younger age and greater education were
      positively associated with e-mail and social media use (p < .05). Most (60%)
      considered telemedicine an excellent medium for health-related patient education.
      DISCUSSION: American Indian patients with DM had access enabling patient
      education via telemedicine. Future work should examine patient technology
      preferences and effectiveness of technology-based education in improving outcomes
      among medically underserved populations.

PMID- 29176113
TI  - Barriers to Health Care among Laotian Americans in Middle Tennessee.
AB  - We examined barriers to health care among Laotian Americans in a Middle Tennessee
      community that included a Laotian-speaking practitioner. A Laotian American
      primary care clinic nurse practitioner surveyed 312 adult Laotian Americans. The
      dependent variable was whether respondents visited (n = 214, 77.8%) or did not
      visit (n = 61,22.2%) primary care providers (PCP) in the last year. Chi-square
      analysis found visiting less likely if respondents were age 18-34 (p < .001),
      born in U.S. (p < .001), spent less time in U.S. (p = .010), never married (p =
      .001), lacked health insurance (p < .001), or lacked a PCP (p < .001). Chi-square
      analysis segmented by age found neither lack of English fluency nor preference
      for Laotian-speaking providers significantly reduced access, possibly because of
      the Laotian practitioner. Logistic regression found individuals with insurance
      five times more likely to visit and individuals with PCP 8.5 times more likely.
      Results support the value of training minority providers.

PMID- 29176114
TI  - Adverse Childhood Experiences (ACE) among American Indians in South Dakota and
      Associations with Mental Health Conditions, Alcohol Use, and Smoking.
AB  - OBJECTIVES: To assess the prevalence of Adverse Childhood Experiences (ACEs) and
      their association with behavioral health in American Indian (AI) and non-AI
      populations in South Dakota. METHODS: We included the validated ACE questionnaire
      in a statewide health survey of 16,001 households. We examined the prevalence of
      ACEs and behavioral health conditions in AI and non-AI populations and
      associations between ACEs and behavioral health. RESULTS: Compared with non-AIs,
      AIs displayed higher prevalence of ACEs including abuse, neglect, and household
      dysfunction and had a higher total number of ACEs. For AIs and non-AIs, having
      six or more ACEs significantly increased the odds for depression, anxiety, PTSD,
      severe alcohol misuse, and smoking compared with individuals with no ACEs.
      CONCLUSIONS: American Indians in South Dakota experience more ACEs, which may
      contribute to poor behavioral health. Preventing and mitigating the effects of
      ACEs may have a significant impact on health disparities in AI populations.

PMID- 29176115
TI  - The Cost-effectiveness Analysis of Nurse-Family Partnership in the United States.
AB  - We evaluated whether Nurse-Family Partnership might serve as a cost-effective
      social policy for improving health. Using data from studies of randomized
      controlled trials as well as real-world data, we conducted a Monte Carlo
      simulation to estimate cost-effectiveness of Nurse-Family Partnership in a
      hypothetical cohort of first-born children in the United States. Analyses were
      conducted in 2015. Were all new mothers eligible for Nurse-Family Partnership,
      the program would produce 0.11 QALYs (95% confidence interval [CI]=0.06, 0.17) at
      an additional cost of $1,021 (95% CI=-$2,831, $4,414) per nurse-visited child's
      lifetime relative to the comparison-group children or $14,642 (95% CI = Savings,
      $71,877) per QALY gained. However, if applied to high-risk mothers, it would
      generate 0.19 QALYs (95% CI = 0.09, 0.44) and a net benefit of $2,764 (95% CI =
      $1,210, $7,092) per nurse-visited child. Nurse-Family Partnership should be
      considered as a policy investment, particularly in an era of investments in the
      social determinants of health.

PMID- 29176118
TI  - Flies come through again, period.

PMID- 29176120
TI  - Social Aetiology of Vd Incidence.

PMID- 29176119
TI  - Immunologic Patterns of Soluble Proteins of Cutaneous Scales in Squamous
      Dermatoses.

PMID- 29176121
TI  - Priapism - A Case Report.

PMID- 29176123
TI  - Primary Raynaud's Disease- A Case Report.

PMID- 29176122
TI  - Lipoid Proteinosis.

PMID- 29176124
TI  - Familial Benign Chronic Pemphigus of Hailey and Hailey.

PMID- 29176125
TI  - Juvenile Bullous Pemphigoid-A Case report.

PMID- 29176126
TI  - Pemphigus Vegetans (A case report with a brief review of literature).

PMID- 29176127
TI  - Toxic Epidermal Necrolysis.

PMID- 29176128
TI  - The De-Sanctis Cacchione Syndrome.

PMID- 29176130
TI  - Scleroderma (A case report).

PMID- 29176129
TI  - Xeroderma Pigmentosa (with review of literature).

PMID- 29176131
TI  - A clinical trial of Dimethothiazine in Pruritic Dermatoses.

PMID- 29176132
TI  - Clinical trial of Dimethothiazine ('Banistyl') in Pruritus associated with
      Dermatological Disorders and Urticaria.

PMID- 29176133
TI  - A case of Secondary Syphilis with iridocyclitis treated with Ledermycin.

PMID- 29176134
TI  - Innovation: An Eternal Theme in the Development of Pediatrics.

PMID- 29176135
TI  - Pediatric Cardiology: Advances Over the Past 2 Years and Future Prospects.

PMID- 29176136
TI  - Plasma Neuropeptide Y Levels in Vasovagal Syncope in Children.
AB  - BACKGROUND: Vasovagal syncope (VVS) is the most common cause of syncope in
      children. Neuropeptide Y (NPY) plays an important role in the regulation of blood
      pressure (BP), as well as myocardial contractility. This study aimed to explore
      the role of plasma NPY in VVS in children. METHODS: Fifty-six children who were
      diagnosed with VVS (VVS group) using head-up tilt test (HUT) and 31 healthy
      children who were selected as controls (control group) were enrolled. Plasma NPY
      concentrations were detected. The independent t-test was used to compare the data
      of the VVS group with those of the control group. The changes in plasma NPY
      levels in the VVS group during the HUT, as well as hemodynamic parameters, such
      as heart rate (HR), BP, total peripheral vascular resistance (TPVR), and cardiac
      output (CO), were evaluated using the paired t-test. Furthermore, the
      correlations between plasma NPY levels and hemodynamic parameters were analyzed
      using bivariate correlation analysis. RESULTS: The BP, HR, and plasma NPY (0.34
      +/- 0.12 pg/ml vs. 0.46 +/- 0.13 pg/ml) levels in the supine position were
      statistically low in the VVS group compared to levels in the control group (all P
      < 0.05). Plasma NPY levels were positively correlated with the HR (Pearson, R =
      0.395, P < 0.001) and diastolic BP (Pearson, R = 0.311, P = 0.003) when patients
      were in the supine position. When patients in the VVS group were in the supine
      position, elevated TPVR (4.6 +/- 3.7 mmHg.min-1.L-1 vs. 2.5 +/- 1.0 mmHg.min-1.L
      1, respectively, P < 0.001; 1 mmHg = 0.133 kPa) and reduced CO (1.0 +/- 0.7 L/min
      vs. 2.4 +/- 1.3 L/min, respectively, P < 0.001) were observed in the positive
      response period compared with baseline values. The plasma NPY levels were
      positively correlated with TPVR (Spearman, R = 0.294, P = 0.028) but negatively
      correlated with CO in the positive-response period during HUT (Spearman, R = 
      0.318, P = 0.017). CONCLUSIONS: Plasma NPY may contribute to the pathogenesis of
      VVS by increasing the TPVR and decreasing the CO during orthostatic regulation.

PMID- 29176137
TI  - Immediate Therapeutic Outcomes and Medium-term Follow-up of Percutaneous Balloon
      Pulmonary Valvuloplasty in Infants with Pulmonary Valve Stenosis: A Single-center
      Retrospective Study.
AB  - BACKGROUND: Percutaneous balloon pulmonary valvuloplasty (PBPV) is the preferred
      therapy for pulmonary valve stenosis (PVS). This study retrospectively reviewed
      recent PBPV outcomes in infants with PVS. The aim of this study was to evaluate
      factors associated with immediate therapeutic outcomes and restenosis during
      medium-term follow-up. METHODS: The study included 158 infants with PVS who
      underwent PBPV from January 2009 to July 2015. Demographic characteristics and
      patient records were reviewed, including detailed hospitalization parameters,
      hemodynamic data before and immediately after balloon dilation, cineangiograms,
      and echocardiograms before PBPV and at each follow-up. All procedures were
      performed by more than two experienced operators. RESULTS: Immediately after
      balloon dilation, the pressure gradient across the pulmonary valve decreased from
      73.09 +/- 21.89 mmHg (range: 43-151 mmHg) to 24.49 +/- 17.00 mmHg (range: 3-92
      mmHg; P < 0.001) and the right ventricular systolic pressure decreased from 95.34
      +/- 23.44 mmHg (range: 60-174 mmHg) to 52.07 +/- 18.89 mmHg (range: 22-134 mmHg;
      P < 0.001). Residual transvalvular pressure gradients of 67.31 +/- 15.19 mmHg
      (range: 50-92 mmHg) were found in 8.2% of patients, indicating poor therapeutic
      effects; 6.4% of patients had variable-staged restenosis at follow-up and 3.8%
      underwent reintervention by balloon dilation or surgical repairs. Further
      analysis demonstrated that the balloon/annulus ratio showed statistically
      significant differences (P < 0.05) among groups with different therapeutic
      effects and between the restenosis and no-stenosis groups. Binary logistic
      regression analysis further revealed that higher balloon/annulus ratio (odds
      ratio: 0.005, 95% confidence interval: 0-0.39) was an independent protective
      factor for restenosis. The rate of severe complications was 1.9%. CONCLUSIONS:
      PBPV is a definitive therapy for infants with PVS based on its effectiveness,
      feasibility, and safety. Restenosis upon medium-term follow-up is relatively
      rare.

PMID- 29176138
TI  - Clinical Manifestations and Amplitude-integrated Encephalogram in Neonates with
      Early-onset Epileptic Encephalopathy.
AB  - BACKGROUND: The patients with early-onset epileptic encephalopathy (EOEE) suffer
      from neurodevelopmental delay. The aim of this study was to analyze the clinical
      manifestations and amplitude-integrated encephalogram (aEEG) characteristics of
      infants with EOEE with onset within the neonatal period, to make early diagnosis
      to improve the prognosis. METHODS: One-hundred and twenty-eight patients with
      neonatal seizure were enrolled and followed up till 1 year old. Sixty-six
      neonates evolved into EOEE were as the EOEE group, the other 62 were as the non
      EOEE (nEOEE) group. Then we compared the clinical and aEEG characteristics
      between the two groups to analyze the manifestations in neonates with EOEE.
      RESULTS: Compared to the nEOEE group, the incidence of daily seizure attacks,
      more than two types of convulsions, more than two antiepileptic drugs (AEDs)
      application, severely abnormal aEEG background, absence of cyclicity, and more
      than two seizures detection were significantly higher in the EOEE group (P <
      0.05) (97% vs. 54.8%; 30.3% vs. 14.5%; 97.0% vs. 25.4%; 39.4% vs. 3.2%; 57.6% vs.
      9.7%; and 56% vs. 3.2%, respectively). Severely abnormal background pattern (odds
      ratio [OR] = 0.081, 95% confidence interval [CI]: 0.009-0.729, P = 0.025) and
      more than two seizures detection by aEEG (OR = 0.158, 95% CI: 0.043-0.576, P =
      0.005) were the independent risk factors for the evolvement into EOEE. The upper
      and lower margins of active sleep (AS) and quiet sleep (QS) were significantly
      higher in EOEE group than those of the control group (P < 0.05) (34.3 +/- 13.6
      vs. 21.3 +/- 6.4; 9.9 +/- 3.7 vs. 6.7 +/- 2.2; 41.2 +/- 15.1 vs. 30.4 +/- 11.4;
      and 11.9 +/- 4.4 vs. 9.4 +/- 4.0; unit: MUV, respectively). AS upper margin was
      demonstrated a higher diagnostic specificity and sensitivity for EOEE than
      another three parameters according to the receiver operating characteristic
      curves; the area under the curve was 0.827. CONCLUSIONS: The clinical
      characteristics of the neonatal seizure which will evolve into EOEE were more
      than two AEDs application, high seizure frequency (daily attack), and more than
      two types of the seizure. Significant high voltage, severely abnormal background,
      absence of cyclicity, and more than two seizures detected on aEEG were the
      meaningful indicators to the prediction of EOEE.

PMID- 29176139
TI  - Preoperative Evaluation and Midterm Outcomes after the Surgical Correction of
      Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery in 50
      Infants and Children.
AB  - BACKGROUND: Anomalous origin of the left coronary artery (LCA) from the pulmonary
      artery (ALCAPA) is a rather rare congenital anomaly that has a profound effect on
      heart function. This study aimed to retrospectively illustrate the perioperative
      clinical features, therapy experience, and midterm outcomes after surgical
      correction, and to determine the value of left ventricular ejection fraction
      (LVEF) and myocardial viability in differentiating critically ill patients among
      infants and children with ALCAPA. METHODS: From April 1999 to March 2013, infants
      and children patients diagnosed with ALCAPA in Beijing Fuwai Hospital were
      analyzed. Clinical data of patients were summarized and retrospectively analyzed.
      All patients were divided into two groups according to LVEF level (Group 1: LVEF
      >50%, or Group 2: LVEF <=50%) to compare perioperative and follow-up variables.
      Effect of myocardial viability evaluated according to myocardial perfusion/18F
      fluorodeoxyglucose (FDG) imaging on the clinical variables was also analyzed.
      RESULTS: A total of 50 patients with ALCAPA (male/female: 29/21; median age: 3.1
      years [range: 4 months to 18 years]) were included. Younger age, lower weight,
      intercoronary collaterals (ICC) dysplasia, ratio of the proximal right coronary
      artery diameter to the aortic root diameter <0.2, and larger cardiothoracic ratio
      (CTR) were more frequently found in Group 2 than those in Group 1. Forty-seven
      patients underwent cardiac surgery. The times of cross-clamp and cardiopulmonary
      bypass were not different between the two groups; however, the duration of
      mechanical ventilation and postoperative Intensive Care Unit stay were longer in
      Group 2 than those in Group 1. Follow-ups were possible in 38 patients (80.9%);
      median time: 84.5 months (range: 49 months to 216 months). There was one late
      sudden death with simple ligation of the LCA at 8 months after surgery. No severe
      complications and reoperation occurred. The relationship of the grades of
      myocardial viability and clinical features was analyzed in 15 patients with
      myocardial perfusion/18F-FDG imaging, and the results showed that myocardial
      viability correlated well with LVEF, CTR, abnormal Q waves, and left ventricular
      end-diastolic dimension. It was not correlated with age, mitral regurgitation,
      and ICC. Heart implantation was decided in one patient with little viable
      myocardium; however, this patient died 2 months after the diagnosis while waiting
      for transplantation. Two patients with no viable myocardium in the area of
      aneurysm had aneurysmectomy concomitantly. CONCLUSIONS: In infants and children
      with ALCAPA, heart function and myocardial viability are closely related to
      clinical features. LVEF and the grades of myocardial viability can differentiate
      high-risk patients before surgery and in the early stage of recovery after
      surgery. The area and extent of myocardial infarction are also crucial in making
      preoperative clinical decisions. However, even in patients with depressed
      ventricular function and severe myocardial infarction, the midterm follow-up
      showed satisfactory recovery of cardiac function after the successful restoration
      of a dual-coronary arterial system.

PMID- 29176140
TI  - Role of Whole-exome Sequencing in Phenotype Classification and Clinical Treatment
      of Pediatric Restrictive Cardiomyopathy.
AB  - BACKGROUND: Restrictive cardiomyopathy (RCM) is the least common cardiomyopathy
      in which the walls are rigid and the heart is restricted from stretching and
      filling properly. Cardiac troponin I (cTnI) mutation-caused myofibril Ca2+
      hypersensitivity has been shown to be associated with impaired diastolic
      function. This study aimed to investigate the linkage between the genotype and
      clinical therapy of RCM. METHODS: Five sporadic pediatric RCM patients confirmed
      by echocardiography were enrolled in this study. Whole-exome sequencing (WES) was
      performed for the cohort to find out candidate causative gene variants. Sanger
      sequencing confirmed the WES-identified variants. RESULTS: TNNI3 variants were
      found in all of the five patients. R192H mutation was shared in four patients
      while R204H mutation was found only in one patient. Structure investigation
      showed that the C terminus of TNNI3 was flexible and mutation on the C terminus
      was possible to cause the RCM. Catechins were prescribed for the five patients
      once genotype was confirmed. Ventricular diastolic function was improved in three
      patients during the follow-up. CONCLUSIONS: Our data demonstrated that TNNI3
      mutation-induced RCM1 is the most common type of pediatric RCM in this study. In
      addition, WES is a reliable approach to identify likely pathogenic genes of RCM
      and might be useful for the guidance of clinical treatment scheme.

PMID- 29176141
TI  - Safflower Extract and Aceglutamide Injection Promoting Recovery of Peripheral
      Innervations via Vascular Endothelial Growth Factor-B Signaling in Diabetic Mice.
AB  - BACKGROUND: Safflower extract and aceglutamide (SA) has been used clinically for
      the treatment of cerebrovascular diseases such as cerebral embolism, hemorrhage,
      and mental deterioration. This study aimed to investigate the effect and
      mechanism of SA injection in the recovery of peripheral innervations of diabetic
      mice. METHODS: The C57BL/6 male mice were divided into four groups: normal
      control group (n = 44), diabetic group (n = 44), diabetic + SA group (diabetic
      mice treated with SA injection, n = 44), and diabetic + SA + vascular endothelial
      growth factor receptor (VEGFR)1-BL group (diabetic mice treated with SA injection
      and VEGFR 1 blocking antibody n = 24). The streptozotocin-induced diabetic mice
      model and injured peripheral nerve mice model were built. The mice with injured
      peripheral nerves were intraperitonealy administered with SA injection for
      successive 21 days. The corneal sensitivity, number of corneal nerve fibers, and
      contents of vascular endothelial growth factor (VEGF)-B and various neurotrophic
      factors such as nerve growth factor (NGF) and glial cell line-derived
      neurotrophic factor (GDNF) in corneal tissue of four groups were observed.
      RESULTS: The diabetic group showed decreased number of corneal nerve fibers,
      compared with the control group (P = 0.002). And compared with the diabetic
      group, the diabetic + SA group showed a significant increase in the number of
      nerve fibers (P = 0.024) and the contents of VEGF-B, NGF, and GDNF in the cornea
      (all P < 0.05). However, when the diabetic mice were treated with the blocking
      antibodies specialized for VEGF-B receptor, the neutralization of VEGFR-1
      completely abolished the increased expression of NGF and GDNF stimulated by SA
      injection. CONCLUSIONS: SA injection could reduce the nerve injury caused by
      diabetic peripheral neuropathy, and its protective effect might be associated
      with the promotion of the expressions of VEGF-B, NGF, and GDNF.

PMID- 29176142
TI  - Efficiency and Productivity of County-level Public Hospitals Based on the Data
      Envelopment Analysis Model and Malmquist Index in Anhui, China.
AB  - BACKGROUND: China began to implement the national medical and health system and
      public hospital reforms in 2009 and 2012, respectively. Anhui Province is one of
      the four pilot provinces, and the medical reform measures received wide attention
      nationwide. The effectiveness of the above reform needs to get attention. This
      study aimed to master the efficiency and productivity of county-level public
      hospitals based on the data envelopment analysis (DEA) model and Malmquist index
      in Anhui, China, and then provide improvement measures for the future hospital
      development. METHODS: We chose 12 country-level hospitals based on geographical
      distribution and the economic development level in Anhui Province. Relevant data
      that were collected in the field and then sorted were provided by the
      administrative departments of the hospitals. DEA models were used to calculate
      the dynamic efficiency and Malmquist index factors for the 12 institutions.
      RESULTS: During 2010-2015, the overall average relative service efficiency of 12
      county-level public hospitals was 0.926, and the number of hospitals achieved an
      effective DEA for each year from 2010 to 2015 was 4, 6, 7, 7, 6, and 8,
      respectively, as measured using DEA. During this same period, the average overall
      production efficiency was 0.983, and the total productivity factor had declined.
      The overall production efficiency of five hospitals was >1, and the rest are <1
      between 2010 and 2015. CONCLUSIONS: In 2010-2015, the relative service efficiency
      of 12 county-level public hospitals in Anhui Province showed a decreasing trend,
      and the service efficiency of each hospital changed. In the past 6 years,
      although some hospitals have been effective, the efficiency of the county-level
      public hospitals in Anhui Province has not improved significantly, and the total
      factor productivity has not been effectively improved. County-level public
      hospitals need to combine their own reality to find their own deficiencies.

PMID- 29176143
TI  - Effect of Cognitive Behavioral Therapy Versus Interpersonal Psychotherapy in
      Patients with Major Depressive Disorder: A Meta-analysis of Randomized Controlled
      Trials.
AB  - BACKGROUND: Practice guidelines have recommended cognitive behavioral therapy
      (CBT) and interpersonal psychotherapy (IPT) as the treatment of choice for major
      depression disorder (MDD). However, whether one therapy is better than the other
      remains inconclusive. The aim of this study was to compare the treatment efficacy
      of the two treatment approaches for MDD. METHODS: Using the terms "cognitive
      behavior therapy or cognitive therapy or CBT or CT or cognitive behavioral
      therapy" and "interpersonal psychotherapy or IPT," we systematically searched
      PubMed, Psyclnfo and Chinese National Knowledge Infrastructure databases up to
      February 2017. The language was restricted to be English and Chinese. Therapeutic
      outcomes, characteristics, and research quality were then extracted and analyzed
      independently. In accessing the included studies, we followed the criteria
      suggested by the Cochrane Handbook for Systematic Reviews of Interventions.
      RESULTS: Data for 946 patients from 10 randomized controlled trials were included
      in the study. Methodological quality was not optimal in most trials. Meta
      analysis showed a mean difference (MD) of -1.31, 95% confidence interval (CI) (
      2.49, -0.12) (P < 0.05) in favor of CBT according to the Beck Depression
      Inventory (BDI), and however, we did not found any statistically significant
      difference between CBT and IPT on the Hamilton Rating Scale for depression (HRSD)
      (MD -0.90, 95% CI [-2.18, 0.38]). Subgroup analyses for the studies in which
      patients were treated only by psychotherapy (MD -1.26, 95% CI [-2.78, 0.35]) and
      for those which offered more sessions of therapies (MD -0.82, 95% CI [-2.23,
      0.59]) showed there was no significant difference between CBT and IPT according
      to BDI. CONCLUSIONS: Differences in treatment efficacy seem to vary according to
      different outcome measures. CBT shows an advantage over IPT for MDD according to
      BDI, and there is no significant difference between the two according to HRSD.
      These results should be interpreted with caution.

PMID- 29176144
TI  - Consensus by Chinese Expert Panel on Chlamydia trachomatis-Resistant and
      Chlamydia trachomatis-Persistent Infection.

PMID- 29176145
TI  - Autoimmune-associated Congenital Heart Block: A New Insight in Fetal Life.
AB  - OBJECTIVE: Congenital heart block (CHB) is a rare but life-threatening disorder.
      More than half of CHB cases are associated with maternal autoimmune, which are
      termed as autoimmune-associated CHB. This review summarized the recent research
      findings in understanding autoimmune-associated CHB, discussed the current
      diagnostic approaches and management strategies, and summarized the problems and
      future directions for this disorder. DATA SOURCES: We retrieved the articles
      published in English from the PubMed database up to January 2017, using the
      keywords including "Autoimmune-associated", "Autoimmune-mediated", and
      "Congenital heart block". STUDY SELECTION: Articles about autoimmune-associated
      CHB were obtained and reviewed. RESULTS: Observational studies consistently
      reported that transplacental maternal antibodies might recognize fetal or
      neonatal antigens in various tissues and result in immunological damages, but the
      molecular mechanisms underlying CHB pathogenesis still need illuminated. Multiple
      factors were involved in the process of atrioventricular block development and
      progression. While several susceptibility genes had been successfully defined,
      how these genes and their protein interact and impact each other remains to be
      explored. With currently available diagnostic tools, fetal ultrasound
      cardiography, and fetal magnetocardiography, most of CHB could be successfully
      diagnosed and comprehensively evaluated prenatally. The efficacy of current
      approaches for preventing the progression and recurrence of CHB and other
      autoimmune-mediated damages was still controversial. CONCLUSIONS: This review
      highlighted the relationships between autoimmune injuries and CHB and
      strengthened the importance of perinatal management and therapy for autoimmune
      associated CHB.

PMID- 29176146
TI  - Establishment of a Comprehensive Evaluation System on Medical Quality Based on
      Cross-examination of Departments within a Hospital.

PMID- 29176147
TI  - Individualized Treatment of Syncope in Children: State-of-the-Art.

PMID- 29176148
TI  - Airway Management in a Child with Goldenhar Syndrome.

PMID- 29176149
TI  - A Novel Mutation of Notch homolog protein 2 gene in a Chinese Family with Hajdu
      Cheney Syndrome.

PMID- 29176150
TI  - Surgical Treatment of Superior Thyroid Artery Aneurysm with Concomitant Thyroid
      Cancer.

PMID- 29176151
TI  - Analysis of 1-year Consecutive Application with Focused Transthoracic
      Echocardiography in Noncardiac Surgery.

PMID- 29176152
TI  - Clinical and Molecular Epidemiology of Invasive Staphylococcus aureus Infections
      in Chinese Children: A Single-center Experience.

PMID- 29176153
TI  - Clinical Analysis of Kawasaki Disease Shock Syndrome.

PMID- 29176154
TI  - An Increase of Heart Rate and Electrocardiographic Changes after Subcutaneous
      Liraglutide.

PMID- 29176155
TI  - Clonorchiasis Complicated with Diffuse Parenchymal Lung Disease in Children.

PMID- 29176156
TI  - Nevus Sebaceous at an Unusual Location: A Rare Presentation.

PMID- 29176157
TI  - Thermo-stimulator a Device To Investigate Cases of Physical Urticaria.

PMID- 29176158
TI  - Clinical and Laboratory Studies on Cutaneous Candidiasis.

PMID- 29176159
TI  - Clinical and Biological Aspects of Skin Aging.

PMID- 29176160
TI  - Dermatomycoses in Hyderabad Area.

PMID- 29176162
TI  - Marital Status and Venereal Diseases.

PMID- 29176161
TI  - Shape of Nail in Postpolioparalysis.

PMID- 29176164
TI  - Unusual Deep Mycoses.

PMID- 29176163
TI  - Sexual Impotency in Males.

PMID- 29176165
TI  - Keratoacanthoma.

PMID- 29176167
TI  - Trichoepithelioma (two clinico-history cases reported).

PMID- 29176166
TI  - Cutaneous Amoebiasis.

PMID- 29176168
TI  - A Case Report of Peutz - Jegher's Syndrome with Review of Literature.

PMID- 29176169
TI  - Ainhum Associated with Psoriasis.

PMID- 29176170
TI  - Cutis Verticis Gyrata.

PMID- 29176171
TI  - A Preliminary Report on Ultrasonic Therapy on Certain Skin Conditions.

PMID- 29176173
TI  - Indian Association of Dermatologists & Venereologists (Annual report for the year
      1969).

PMID- 29176172
TI  - Role of Intralesional Corticosteroid Therapy in Pemphigus.

PMID- 29176174
TI  - Indian Association of Dermatologists & Venereologists XI Annual Conference held
      in January, 1969 at Hyderabad.

PMID- 29176175
TI  - Patterns of Soluble Proteins in Cutaneous Scales.

PMID- 29176176
TI  - A Study of Donovanosis (Granuloma Venereum).

PMID- 29176177
TI  - Scleroma in Delhi Area.

PMID- 29176178
TI  - Observations on the Management of Lepra Reaction.

PMID- 29176179
TI  - Norwegian Scabies.

PMID- 29176180
TI  - Sun Screening Effect of Para Amino Benzoic Acid Given Orally and Its Role in the
      Treatment of Hyperpigmented Patches on Face.

PMID- 29176181
TI  - Effects of Tolbutamide on Vitiligo and Photosensitising Action.

PMID- 29176182
TI  - Use of Griseofulvin Other Than Anti-fungal.

PMID- 29176183
TI  - Principles of Genetics& Classification of Inherited Disorders of Skin.

PMID- 29176185
TI  - Trichostasis Spinulosa.

PMID- 29176184
TI  - Subcorneal Pustular Dermatosis.

PMID- 29176186
TI  - Case Report of Psoriasis with Rheumatoid Arthritis with Polyneuritic Leprosy.

PMID- 29176187
TI  - Current and emerging trends in prostate cancer immunotherapy.

PMID- 29176188
TI  - Twenty Five Years of Dermatovenereolaigy in India.

PMID- 29176189
TI  - Study on the Perforation of Palate.

PMID- 29176190
TI  - Ecology of V. D. Incidence.

PMID- 29176192
TI  - Indian Association of Dermatologists & Venereologists Scientific Programme of
      Twelfth Annual Conference.

PMID- 29176191
TI  - Prof. Kandhari.

PMID- 29176193
TI  - From Our Bookshelf.

PMID- 29176194
TI  - Neurcsyphilis.

PMID- 29176195
TI  - Congenital Ectodermal Defect.

PMID- 29176196
TI  - Chronic Benign Pemphigus of Hailey and Hailiey.

PMID- 29176197
TI  - Familial Hypercholestrolemic Xanthomatosis.

PMID- 29176198
TI  - Granuloma Venereum Treated with "reverin".

PMID- 29176199
TI  - Clinical Evaluation of Tavegyl (HS-592) in Skin Disorders.

PMID- 29176201
TI  - XI Annual Conference.

PMID- 29176200
TI  - Presidential Address.

PMID- 29176202
TI  - Mycoplasma in Lesions of Pemphigus.

PMID- 29176204
TI  - Leprosy Survey: Tirupati 1965.

PMID- 29176203
TI  - Auto-immune Mechanisms in Dermatology.

PMID- 29176205
TI  - Cutis Verticis Gyrata Due to Chronic Folliculitis.

PMID- 29176207
TI  - Isolation of a Local Strain of the Virus of Lymphogranuloma Venereum in the Yolk
      Sac of Growing Chick Embryo.

PMID- 29176206
TI  - Buschke-loewenstein Tumour of Penis.

PMID- 29176208
TI  - Biochemical Studies on T. Quinckeanum.

PMID- 29176209
TI  - Epidermolysis Bullosa.

PMID- 29176210
TI  - Syphilitic Leuco-melanoderma - Report of 3 Cases.

PMID- 29176211
TI  - Pseudoxanthoma Elasticum (PXE) Report of Three Cases.

PMID- 29176212
TI  - Photosensitivity with Demethylchlortetracycline.

PMID- 29176213
TI  - Multiple Leprotic Nerve Abscesses in a Child.

PMID- 29176215
TI  - The Proteolytic Activity of Non-pathogenic Fungi, Part II.

PMID- 29176214
TI  - The Proteolytic Activity of Non Pathogenic and Pathogenic Fungi.

PMID- 29176216
TI  - Clinical Pattern of Pityriasis Versicolor.

PMID- 29176218
TI  - A Topical Tar-steroid Combina- Tion in Dermatological Management.

PMID- 29176217
TI  - Genetic Constitution and Thu Causation of Disease.

PMID- 29176220
TI  - Case Report of Bullous Type of Dermatitis Herpetiformis Treated with Dapsone.

PMID- 29176219
TI  - Donovanosis At Kakinada.

PMID- 29176221
TI  - A Case of Donovanosis Resistant To Streptomycin But Responded To Tetracycline.

PMID- 29176223
TI  - A New Convenient Egg-enriched Medium For the Cultural Diagnosis of Gonorrhoea.

PMID- 29176222
TI  - A Case Report of Gonococca Urethritis Resistant to Most Common Antibiotics
      Treated with Chloramphenicol with Fever Therapy.

PMID- 29176225
TI  - Seasonal Leg Ulcer.

PMID- 29176224
TI  - Hair Penetration Test in Relation To Hairs with Various Structural Abnormalities
      and Hirsutism Hairs.

PMID- 29176226
TI  - Prostitution and Venereal Disease.

PMID- 29176228
TI  - Symposium on Venereal Disease Stresses Role of Physician in Eradicting V. D.

PMID- 29176227
TI  - Pigmentation of the Buccal Mucosa.

PMID- 29176229
TI  - Indian Association of Dermatologists and Venereologists (Central Council) ...

PMID- 29176230
TI  - Serum Cholesterol in Skin Diseases.

PMID- 29176231
TI  - Clinical Pattern of Psoriasis in Punjab.

PMID- 29176232
TI  - Lipogranulomatosis Subcutanea.

PMID- 29176233
TI  - The Proposed Classification of Hypo and Depigmentary Skin Disorders.

PMID- 29176235
TI  - Penicillin Resistant Gonorrhoea in Trivandrum.

PMID- 29176234
TI  - Vitiligo and Vitamin B Complex.

PMID- 29176236
TI  - Pyoderma Gangrenosum.

PMID- 29176238
TI  - Editorial.

PMID- 29176237
TI  - 8th All India Conference.

PMID- 29176240
TI  - Principles of Immunology-A Brief Review Part-I Basic Immunology.

PMID- 29176239
TI  - Study of Proteolytic Enzymes, Epidermal Extracts and Cantharidin in Producing
      Cutaneous Blisters.

PMID- 29176241
TI  - Principles of Immunology-A Brief Review Part-II Clinical Immunology.

PMID- 29176243
TI  - Epidermolysis Bullosa.

PMID- 29176242
TI  - Epidermolysis Bullosum Simplex Simulating Aplasia Cutis.

PMID- 29176244
TI  - Cutaneous Manifestations of Tuberous Sclerosis.

PMID- 29176245
TI  - Erythema Ab Igne-report of a Case.

PMID- 29176246
TI  - A Rare Manifestation of Xeroderma Pigmentosum.

PMID- 29176248
TI  - Basal Cell Carcinoma Treated with Topical Chemotherapy.

PMID- 29176247
TI  - A Case Report of Incontinentia Pigmenti.

PMID- 29176249
TI  - Partial unilateral lentiginosis with ipsilateral ocular involvement and seizures.

PMID- 29176250
TI  - Eosinophilic dermatoses (exaggerated insect bite-like reaction) associated with
      hematological malignancy: Report of three cases.

PMID- 29176251
TI  - Generalized Dowling-Degos disease with hypopigmented lesions: A diagnostic
      challenge.

PMID- 29176252
TI  - Cirsoid aneurysm of scalp.

PMID- 29176253
TI  - Dermoscopy and scanning electron microscopy in two cases with hair shaft damage
      secondary to hair straightening.

PMID- 29176255
TI  - Trichomoniasis.

PMID- 29176254
TI  - Vitiligo with Some Indigenous Drugs.

PMID- 29176256
TI  - Herpes Zoster and Chicken Pox.

PMID- 29176257
TI  - Granuloma Pyogenicum.

PMID- 29176258
TI  - Acanthosis Nigricans.

PMID- 29176259
TI  - A Method of Repoting Adverse Drug Reactions.

PMID- 29176260
TI  - The Hopeless Patient.

PMID- 29176262
TI  - Elevated Plasma Levels of Gas6 Are Associated with Acute Lung Injury in Patients
      with Severe Sepsis.
AB  - Acute lung injury (ALI) is one of the complications of severe sepsis, causing
      sudden deaths. However, information regarding predictive factors for the onset of
      ALI in severe sepsis is limited. Growth arrest-specific gene 6 (Gas6) is secreted
      by endothelial cells and is important for the activation of endothelium during
      inflammation. This study aimed to investigate the predictive effect of plasma
      Gas6 in patients with severe sepsis. Collection of plasma samples was carried out
      from 129 participants with severe sepsis following with or without ALI
      development. We found that the elevated levels of Gas6, interleukin-6 and -8 (IL
      6 and IL-8) in plasma were associated with the ALI development (P = 0.003, 0.002,
      and 0.004, respectively). We also observed the robust correlation between the
      plasma level of Gas6 and the following ALI development to adjustment for sepsis
      and administration of vasopressor. Between patients with ALI (n = 18) and those
      without ALI (n = 111), Gas6 and the Lung Injury Prediction Score (LIPS) showed
      promising discrimination (AUROC, 0.74 and 0.68, respectively), and in combination
      with these two indexes, the AUROC was increased to 0.86 (vs. 0.74, P = 0.05),
      while soluble receptor for advanced glycation end products (sRAGE) and Willebrand
      factor (vWF) in plasma showed no predictive value for of ALI. Collectively, our
      findings indicate that higher levels of Gas6 in plasma are obviously correlated
      with ALI development. An early increase in the plasma Gas6 level suggests that
      endothelial injury is a key link in the pathogenesis of ALI.

PMID- 29176261
TI  - Reduced Vitamin D Receptor on Circulating Endothelial Progenitor Cells: A New
      Risk Factor of Coronary Artery Diseases.
AB  - AIM: Endothelial progenitor cells (EPCs) are shown to participate in the
      pathological processes of atherosclerosis. While Vitamin D and its receptor axis
      might exert some effects on EPCs' function. But their exact relationship with
      clinical patients is still elusive, which inspired us to explore the potential
      association of vitamin D receptor (VDR) expression on circulating EPCs and serum
      vitamin D levels among patients with coronary artery disease (CAD). METHODS: Two
      hundred patients with CAD after their admission to hospital and one hundred
      healthy controls were enrolled. Medical history data were retrieved and fresh
      blood samples were collected for flow cytometry analysis. VDR expressions on EPCs
      were evaluated according to the standardized protocol. Logistic regression
      analysis was used to investigate the potential risk factor of CAD. RESULTS: CAD
      patients were found to have lower log10VDR-MFIs than those of control group,
      especially for patients with diabetes (p<0.001). Log10VDR-MFIs were inversely
      correlated with glycated hemoglobin (R=-0.472, p<0.001), and while EPCs
      challenged with high glucose had lower VDR expression. Multivariate logistic
      regression analysis revealed that lower log10VDR-MFIs were independently
      associated with the risk of CAD (OR=0.055, p=0.008). CONCLUSION: A significant
      decrease of VDR expression on circulating EPCs was observed among CAD patients,
      particularly among those also with diabetes. VDR expression on EPCs was
      independently negatively correlated with HbA1c and high glucose decreased EPCs'
      VDR expression. Low levels of VDR expression on circulating EPCs might serve as a
      potential risk factor of CAD.

PMID- 29176263
TI  - A study on periostin involvement in the pathophysiology of canine atopic skin.
AB  - Atopic dermatitis (AD) is a chronic, pruritic, and allergic skin disease in
      humans and animals, particularly dogs. Canine AD (cAD) has received attention as
      a spontaneous atopic animal model because domesticated dogs inhabit a human
      environment, and cAD shares several clinicopathological features with human AD
      (hAD). In hAD, periostin (PO) is suggested to play a critical role in the
      enhancement and chronicity of allergic skin inflammation; however, PO involvement
      in the pathogenesis of cAD is unknown. Here we aimed to clarify PO involvement in
      the pathophysiology of cAD and focused on the inducing factor and function of PO
      in canine atopic skin. Using double-labeled in situ hybridization (ISH),
      interleukin (IL)-13 mRNA-positive cells were detected near the keratinocytes and
      dermal fibroblasts expressing PO mRNA in atopic skin. Using an in vitro assay, IL
      13 induced PO gene expression in both canine dermal fibroblasts and
      keratinocytes. PO enhanced in vitro growth of canine keratinocytes. Moreover,
      among PO-induced genes in cultured canine keratinocytes detected using a
      microarray, we identified IL-25 as a possible mediator in canine atopic skin. In
      addition, real time polymerase chain reaction (PCR) analysis revealed
      upregulation of IL-25 gene expression in PO-stimulated keratinocytes. These data
      suggest that IL-13 possibly derived from T helper 2 (Th2) cells stimulates PO
      production in both keratinocytes and fibroblasts, and then PO may play a critical
      role in the pathophysiology of cAD, particularly in the enhancement and
      chronicity of skin lesions via IL-25.

PMID- 29176264
TI  - Efficacy of Chondroitin Sulfate for Painful Knee Osteoarthritis: A One-Year,
      Randomized, Double-Blind, Multicenter Clinical Study in Japan.
AB  - We explored the effects of chondroitin sulfate on knee osteoarthritis in a one
      year, randomized, double-blind, dose-comparison study. Patients with painful,
      Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral
      chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group)
      or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index
      and visual analog scale for pain. We made subgroup analyses according to
      background symptom severity (Lequesne's index >=8 or <8) in 73 patients. Serum
      level of cartilage oligomeric matrix protein and hyaluronic acid were also
      determined. In the subgroup with severe symptoms (Lequesne's index >=8), the
      chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months'
      therapy. However, no dose-related effects were found on cartilage oligomeric
      matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good
      tolerability. We conclude that chondroitin sulfate is useful for pain control in
      knee osteoarthritis.

PMID- 29176265
TI  - The Effect of Ethanol on the Hydrolysis of Ester-Type Drugs by Human Serum
      Albumin.
AB  - Human serum albumin (HSA) has two major ligand-binding sites, sites I and II, and
      hydrolyzes compounds at both sites. Although the hydrolytic interaction of ester
      type drugs with other drugs by HSA has been reported, there are only a few
      studies concerning the effect of pharmaceutical excipients on the hydrolysis of
      ester-type drugs by HSA. In the present study, we investigated the effect of
      ethanol (2 vol%; 345 mM) on the hydrolysis of aspirin, p-nitrophenyl acetate, and
      olmesartan medoxomil, which are ester-type drugs, with 4 different lots of HSA
      preparations. The hydrolysis activities of HSA toward aspirin, p-nitrophenyl
      acetate, and olmesartan medoxomil were measured from the pseudo-first-order
      degradation rate constant (kobs) of salicylic acid, p-nitrophenol, and
      olmesartan, respectively, which are the HSA-hydrolyzed products. Ethanol
      inhibited hydrolysis of aspirin by HSA containing low levels of fatty acids, but
      not by fatty acid-free HSA. Ethanol inhibited hydrolysis of p-nitrophenyl acetate
      by both fatty acid-free HSA and HSA containing low levels of fatty acids. In
      contrast, the hydrolysis of olmesartan medoxomil by HSA was insignificantly
      inhibited by ethanol, but inhibited not only by warfarin and indomethacin but
      also by naproxen, which are site I binding drugs and a site II binding drug,
      respectively. These results suggest that the inhibitory action of ethanol on the
      hydrolysis of ester-type drugs by HSA differs between site I binding drugs and
      site II binding drugs.

PMID- 29176266
TI  - Fibrin Clot Architecture in Acute Ischemic Stroke Treated With Mechanical
      Thrombectomy With Stent-Retrievers - Cohort Study.
AB  - BACKGROUND: The composition of intra-arterial clots might influence the efficacy
      of mechanical thrombectomy (MT) in ischemic stroke (IS) due to the acute
      occlusions within large cerebral arteries. The aims were to assess the factors
      associated with blood clot structure and the impact of thromboembolus structure
      on MT using stent-retrievers in patients with acute large artery IS in the
      anterior circulation.Methods and Results:In an observational cohort study, we
      studied the components of intra-arterial clots retrieved from large cerebral
      arteries in 80 patients with acute IS treated with MT with or without i.v.
      thrombolysis (IVT). Histology of the clots was carried out without knowledge of
      the clinical findings, including the treatment methods. The components of the
      clots, their age, origin and semi-quantitative graded changes in the architecture
      of the fibrin components (e.g., "thinning") were compared via neuro
      interventional, clinical and laboratory data. The most prominent changes in the
      architecture of the fibrin components in the thromboemboli were associated with
      IVT (applied in 44 patients; OR, 3.50; 95% CI: 1.21-10.10, P=0.02) and platelet
      count (OR, 2.94; 95% CI: 1.06-8.12, P=0.04). CONCLUSIONS: In patients with large
      artery IS treated with the MT using stent-retrievers, bridging therapy with IVT
      preceding MT and higher platelet count were associated with significant changes
      of the histological structure of blood clots.

PMID- 29176267
TI  - Examination of validity of a conditioned odor aversion (COA) procedure using low
      dose of organic solvent as an applied procedure of the conditioned taste
      aversion.
AB  - Smell of very low dose of chemical might evoke subjective physical symptoms in
      human by some process of learning named the aversion conditioning. But few
      scientific evidences of the hypothesis have been reported so far. Validity of
      conditioned odor aversion (COA) using low-doses of organic solvent as odor
      conditioned stimulus (CS) was examined. In conditioning phase, water-deprived
      male Sprague-Dawley rats were presented low, medium or high dose solution for 30
      min followed by 0.3 M Lithium Chloride (LiCl) solution or saline injection. The
      xylene solution and drink water were simultaneously provided on the next day as
      two-bottle test. Consumption of medium dose of xylene solution was significantly
      decreased in LiCl injection group as compared with saline group. There was no
      difference between LiCl and saline injected animals in low group. Animals in high
      dose did not access to xylene even on the conditioning. These results indicate
      that animals showed high sensitivity for discrimination against concentration of
      xylene and that the medium dose of xylene functioned as the CS. We concluded that
      the COA used in the present study may be one of useful procedures to investigate
      olfaction of animal.

PMID- 29176268
TI  - Hemodynamic Implications of Carbon Monoxide (CO) and Nitrogen Oxide (NO) during
      Living Donor Liver Transplantation.
AB  - Carbon monoxide (CO) and nitrogen oxide (NO) affect vasodilation and cause
      hemodynamic change. Hemodynamic instability due to liver transplantation may
      result in poor prognosis of graft. This study investigated the hemodynamic
      implications of CO and NO levels measured using carboxyhemoglobin (COHb) and
      methemoglobin (MetHb) during living donor liver transplantation (LDLT). The
      hemodynamic instability with a pressor dose (norepinephrine equivalent) was
      estimated 1 hour after graft reperfusion. COHb and MetHb were used as indexes of
      CO and NO, and were measured using an arterial blood gas analyzer. One hundred
      and ten recipients who underwent LDLT from May 2011 to July 2013 were selected.
      Recipients were divided into high (>= 1.9%) and low (< 1.9%) COHb groups with
      COHb concentrations at 5 minutes after reperfusion. Recipients were also divided
      into high (>= 0.4%) and low (< 0.4%) MetHb groups with MetHb concentrations at 30
      minutes after reperfusion. Data are presented as mean +/- standard deviation or
      number (percentage). Model for End-stage Liver Disease (MELD) scores were
      different for the two COHb groups (low: 13.4 +/- 9.0 vs. high: 19.7 +/- 10.6, p <
      0.001), and pressor doses adjusted by MELD scores were also different between the
      two COHb groups (low: 0.09 +/- 0.01 MUg/kg/min vs. high: 0.14 +/- 0.01
      MUg/kg/min, p = 0.029). By contrast, pressor doses and MELD scores were not
      different between the two MetHb groups. In conclusion, CO rather than NO has
      hemodynamic implications during LDLT. Therefore, the increase in COHb during LDLT
      is predictive of hemodynamic instability.

PMID- 29176270
TI  - An Unusual Foreign Body in the Heart: A Case Report.
AB  - Penetrating foreign bodies in the heart is rare and may lead to life-threatening
      complications. Early diagnosis and removal are crucial for these rare cases. We
      report a case of accidental penetrating sewing needle in the right ventricle. The
      needle was successfully removed without open heart surgery and cardiopulmonary
      bypass (CPB), after accurate localization using transthoracic echocardiography
      (TTE).

PMID- 29176269
TI  - Clinical and Radiological Outcomes of Microscopic Lumbar Foraminal Decompression:
      A Pilot Analysis of Possible Risk Factors for Restenosis.
AB  - A single-center retrospective comparative study was designed to identify the risk
      factors for restenosis of lumbar foraminal stenosis (LFS) after microscopic
      foraminal decompression (MFD). 21 consecutive patients who underwent single-level
      MFD with an average of 19-month follow-up were divided into two study groups
      based on clinical outcomes; group 1 (7 patients with poor outcomes requiring
      revision surgery), group 2 (14 patients with good outcomes with no revision
      surgery required). Changes of lumbar spinal alignment on plain standing
      radiographs were compared and analyzed between two study groups to investigate
      the pathology and risk factors associated with restenosis after MFD. Preoperative
      disc wedging (DW) angle was significantly larger in group 1 than in group 2 (3.5
      +/- 1.0 degrees  vs 1.1 +/- 0.2 degrees , P < 0.01). Postoperatively, disc height
      (DH) and foraminal height (FH) decreased (P < 0.05), and DW deteriorated (P <
      0.01) significantly in group 1, while there were no significant changes in group
      2. Lumbar lordosis (LL) remarkably improved postoperatively in group 2 (24.7 +/-
      8.0 to 32.0 +/- 7.0, P < 0.001), contrary to limited improvement in group 1 (25.1
      +/- 9.2 to 27.0 +/- 12.0, P = 0.45). Postoperative LL is a predictive factor for
      restenosis after MFD. Decrease in DH or progression of DW was contributing to
      restenosis. LFS presenting with large DW and lumbar degenerative kyphosis should
      be excluded from surgical indications for MFD without instrumented fusion,
      considering the high recurrence rate.

PMID- 29176271
TI  - Patterns of Ultraviolet Radiation Exposure and Skin Cancer Risk: the E3N-SunExp
      Study.
AB  - BACKGROUND: While ultraviolet (UV) radiation exposure is a recognized risk factor
      for skin cancer, associations are complex and few studies have allowed a direct
      comparison of exposure profiles associated with cutaneous melanoma, basal-cell
      carcinoma (BCC), and squamous-cell carcinoma (SCC) within a single population.
      METHODS: We examined associations between UV exposures and skin cancer risk in a
      nested case-control study within E3N, a prospective cohort of 98,995 French women
      born in 1925-1950. In 2008, a lifetime UV exposure questionnaire was sent to all
      reported skin cancer cases and three controls per case, which were matched on
      age, county of birth, and education. Analyses were performed using conditional
      logistic regression and included 366 melanoma cases, 1,027 BCC cases, 165 SCC
      cases, and 3,647 controls. RESULTS: A history of severe sunburns <25 years was
      associated with increased risks of all skin cancers (melanoma: OR 2.7; BCC: OR
      1.7; SCC: OR 2.0 for >=6 sunburns vs. none), while sunburns >=25 years were
      associated with BCC and SCC only. While high-sun protection factor sunscreen use
      before age 25 was associated with lower BCC risk (Ptrend = 0.02), use since age
      25 and reapplication of sunscreen were associated with higher risks of all three
      types of skin cancer. There were positive linear associations between total UV
      score and risks of BCC (Ptrend = 0.01) and SCC (Ptrend = 0.09), but not melanoma.
      While recreational UV score was strongly associated with BCC, total and
      residential UV scores were more strongly associated with SCC. CONCLUSIONS:
      Melanoma, BCC, and SCC are associated with different sun exposure profiles in
      women.

PMID- 29176273
TI  - Importance of Achieving a "Fit" Cardiorespiratory Fitness Level for Several Years
      on the Incidence of Type 2 Diabetes Mellitus: A Japanese Cohort Study.
AB  - BACKGROUND: The "Physical Activity Reference for Health Promotion 2013" provides
      "fit" reference values for cardiorespiratory fitness (CRF) for good health. The
      importance of achieving a fit CRF level for several years on the subsequent
      prevention of type 2 diabetes mellitus (T2DM) remains to be clarified. METHODS:
      This cohort study was conducted in 2,235 nondiabetic males aged 21 to 59 years,
      enrolled in April 1986 through March 1987. We calculated the ratio of the area
      under the curve (AUCratio) for actual measured values and the AUC for the
      reference values of CRF in each individual during an 8-year measurement period
      before the baseline. According to whether they met a fit CRF level or not,
      participants were categorized into groups based on the AUCratio (FitAUC or
      UnfitAUC) and initial CRF (Fitinitial or Unfitinitial), respectively. T2DM was
      evaluated on health checkups until March 2010. RESULTS: During the follow-up
      period, 400 men developed T2DM. After adjustment for confounders, as compared
      with those in the FitAUC group, the hazard ratio (HR) for those in the UnfitAUC
      group was 1.33 (95% confidence interval [CI], 1.06-1.65). A combined analysis
      with the categories of initial value and AUCratio showed that, compared with the
      Fitinitial and FitAUC group, the HRs of Fitinitial and UnfitAUC, Unfitinitial and
      FitAUC, and Unfitinitial and UnfitAUC groups were 1.41 (95% CI, 0.99-2.00), 1.18
      (95% CI, 0.81-1.70), and 1.40 (95% CI, 1.08-1.83), respectively. CONCLUSION:
      Achievement of a fit CRF level established in the Japan physical activity
      guideline for several years was associated with lower subsequent risk of T2DM.

PMID- 29176272
TI  - Modification of the Associations of Alcohol Intake With Serum Low-Density
      Lipoprotein Cholesterol and Triglycerides by ALDH2 and ADH1B Polymorphisms in
      Japanese Men.
AB  - BACKGROUND: Although beneficial associations have been reported between moderate
      alcohol intake and the serum lipid profile, it is unclear whether polymorphisms
      in alcohol-metabolizing enzymes can modify these associations. Here, we assessed
      the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their
      combination on these associations. Furthermore, we examined if the findings for
      ALDH2 could be replicated. METHODS: We categorized 889 male participants in the
      Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups
      based on presence or absence of minor allele(s) or four groups based on genotype
      combinations. We performed regression analyses of serum lipid concentrations on
      alcohol intake, with multivariable adjustment. The replication study was
      conducted among 2,562 men in the Shizuoka part of the J-MICC Study. RESULTS: The
      ALDH2 Glu/Lys or Lys/Lys groups showed significant decreases in serum low-density
      lipoprotein (LDL) cholesterol with increasing alcohol consumption; the
      coefficient per intake increase of 10 g/day was -2.49 mg/dL (95% confidence
      interval [CI], -3.85 to -1.13), and a significant interaction with the
      polymorphism was confirmed (P for interaction = 0.006). This inverse correlation
      was more evident among the ADH1B His/His + ALDH2 Glu/Lys or Lys/Lys groups (-3.24
      mg/dL, 95% CI, -5.03 to -1.45). Serum triglycerides were positively associated
      with alcohol consumption in the ADH1B His/His group (P for interaction = 0.020).
      The stronger association between serum LDL cholesterol and alcohol consumption in
      the ALDH2 Glu/Lys or Lys/Lys groups was replicated. CONCLUSIONS: The ALDH2
      Glu504Lys polymorphism can modify the association between alcohol intake and
      serum LDL cholesterol in Japanese men.

PMID- 29176276
TI  - ?

PMID- 29176274
TI  - Increased Incidence of Visual Field Abnormalities as Determined by Frequency
      Doubling Technology Perimetry in High Computer Users Among Japanese Workers: A
      Retrospective Cohort Study.
AB  - BACKGROUND: This retrospective cohort study primarily aimed to investigate the
      possible association of computer use with visual field abnormalities (VFA) among
      Japanese workers. METHODS: The study included 2,377 workers (mean age 45.7
      [standard deviation, 8.3] years; 2,229 men and 148 women) who initially exhibited
      no VFA during frequency doubling technology perimetry (FDT) testing. Subjects
      then underwent annual follow-up FDT testing for 7 years, and VFA were determined
      using a FDT-test protocol (FDT-VFA). Subjects with FDT-VFA were examined by
      ophthalmologists. Baseline data about the mean duration of computer use during a
      5-year period and refractive errors were obtained via self-administered
      questionnaire and evaluations for refractive errors (use of eyeglasses or contact
      lenses), respectively. RESULTS: A Cox proportional hazard analysis demonstrated
      that heavy computer users (>8 hr/day) had a significantly increased risk of FDT
      VFA (hazard ratio [HR] 2.85; 95% confidence interval [CI], 1.26-6.48) relative to
      light users (<4 hr/day), and this association was strengthened among subjects
      with refractive errors (HR 4.48; 95% CI, 1.87-10.74). The computer usage history
      also significantly correlated with FDT-VFA among subject with refractive errors
      (P < 0.05), and 73.1% of subjects with FDT-VFA and refractive errors were
      diagnosed with glaucoma or ocular hypertension. CONCLUSIONS: The incidence of FDT
      VFA appears to be increased among Japanese workers who are heavy computer users,
      particularly if they have refractive errors. Further investigations of
      epidemiology and causality are warranted.

PMID- 29176275
TI  - Patterns and Levels of Sedentary Behavior and Physical Activity in a General
      Japanese Population: The Hisayama Study.
AB  - BACKGROUND: The purpose of this cross-sectional study was to describe the
      patterns and levels of sedentary time and physical activity (PA) in a general
      Japanese population. METHODS: A total of 1,740 community-dwelling Japanese adults
      aged >=40 years participated in this study. Sedentary time and PA were assessed
      for 7 consecutive days using a tri-axial accelerometer. Daily patterns and levels
      of sedentary time and PA were calculated by sex, age group (40-64, 65-74, and
      >=75 years), and body mass index (BMI; <25 and >=25 kg/m2). RESULTS: Participants
      spent half of their waking time being sedentary, 32.7% of which was accumulated
      in prolonged bouts >=30 minutes, versus only 54.4 minutes/day (7% of waking time)
      as moderate-to-vigorous PA (MVPA) (11.8 minutes/day in bouts >=10 minutes). In
      addition to total sedentary time, men had longer prolonged sedentary bouts and
      fewer breaks per sedentary hour than women. Similar trends were observed in
      participants aged >=75 years and those with a higher BMI (>=25 kg/m2) compared to
      those with a younger age and lower BMI. Moreover, participants aged >=75 years
      and those with a higher BMI accumulated fewer MVPA minutes in bouts >=10 minutes.
      Only 34.8% of the population met the recommended level of >=150 minutes/week MVPA
      in bouts >=10 minutes. CONCLUSION: Japanese adults accumulated a large proportion
      of total sedentary time in prolonged bouts but few minutes in sustained bouts of
      MVPA, and few of them met the current PA guideline.

PMID- 29176277
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PMID- 29176279
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PMID- 29176280
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PMID- 29176281
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PMID- 29176282
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PMID- 29176283
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PMID- 29176284
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PMID- 29176286
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PMID- 29176285
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PMID- 29176288
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PMID- 29176287
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PMID- 29176290
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PMID- 29176289
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PMID- 29176292
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PMID- 29176294
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PMID- 29176293
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PMID- 29176295
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PMID- 29176296
TI  - Periostin Expression in Non-Small Cell Lung Cancer: Clinical Significance.
AB  - Periostin is an extracellular matrix N-glycoprotein that is a major constituent
      of the desmoplastic stroma around solid tumors. Periostin promotes tumor invasion
      and metastasis via epithelial-mesenchymal transition. The aims of this study were
      to evaluate periostin expression immunohistochemically and quantitatively in
      patients with non-small cell lung cancer (NSCLC) and to assess any associations
      with clinical features and prognosis. A total of 184 specimens of NSCLC tissue
      were investigated, including 134 adenocarcinomas, 39 squamous cell carcinomas,
      and 11 other histologic subtypes. The intra-tumoral periostin expression area in
      each captured field was calculated using the image processing integration
      software WinROOF. The mean periostin expression score was classified as high or
      low by the median value of its expression area. Univariate analysis demonstrated
      that gender, tumor size, T status, N status, stage, histologic type, smoking
      habits, percent vital capacity, 1% forced expiratory volume, and pleural invasion
      were each significantly associated with periostin scores. Multivariate analysis
      revealed that high periostin expression score was an independent prognostic
      factor significantly associated with decreased cancer-specific survival (HR,
      3.65; 95% CI, 1.04-12.84; P=0.0439). We concluded that intratumoral periostin
      expression was an independent prognostic factor for NSCLC.

PMID- 29176297
TI  - Treatment of a Large Pharyngeal Venous Malformation using Transoral
      Sclerotherapy.
AB  - Management of venous malformation (VM) in the pharynx is challenging because of
      difficulties in needle access and the presence of nerves as well as other
      critical anatomical structures around the lesion. We describe the successful
      treatment of a large pharyngeal VM using transoral sclerotherapy. The patient, a
      21-yearold male, visited our hospital for sclerotherapy treatment consultation
      after complaining of difficulty in swallowing because of a pharyngeal VM.
      Transoral sclerotherapy was successful, and the symptoms showed complete
      alleviation. Using a flat detector-equipped angiographic C-arm CT (CACT) enabled
      the precise assessment of sclerosant placement, facilitating safer sclerotherapy
      in the pharynx.

PMID- 29176298
TI  - Smaller effect of propofol than sevoflurane anesthesia on dopamine turnover
      induced by methamphetamine and nomifensine in the rat striatum: an in vivo
      microdialysis study.
AB  - Volatile anesthetics accelerate dopamine turnover in the brain, especially when
      used in conjunction with psychotropic agents such as methamphetamine and
      nomifensine. The effect of intravenous propofol anesthesia on the extracellular
      dopamine concentrations is unclear. The aim of this study was to compare the
      effect of two anesthetics on the extracellular concentrations of dopamine and
      metabolites using an in vivo microdialysis model. Male Sprague Dawley rats were
      implanted with a microdialysis probe into the right striatum. The probe was
      perfused with modified Ringer's solution, and the dialysate was directly injected
      into a high-performance liquid chromatography system every 20 min. The rats were
      intraperitoneally administered saline, methamphetamine at 2 mg/kg, or nomifensine
      at 10 mg/kg. After treatment, the rats were anesthetized with intravenous
      propofol (20 mg/kg followed by 25 or 50 mg/kg/h) or inhalational sevoflurane
      (2.5%) for 1 h. Propofol showed no effect on the extracellular concentration of
      dopamine during anesthesia; however, propofol decreased the dopamine
      concentration after anesthesia in the high-dose group. Sevoflurane anesthesia
      increased the concentration of metabolites. Systemic administration of
      methamphetamine and nomifensine increased the extracellular concentration of
      dopamine. Sevoflurane anesthesia significantly enhanced the increase in the
      dopamine concentration induced by both methamphetamine and nomifensine, whereas
      propofol anesthesia showed no effect on the methamphetamine- and nomifensine
      induced dopamine increase during anesthesia. The enhancing effect of psychotropic
      agent-induced acceleration of dopamine turnover was smaller for propofol
      anesthesia than for sevoflurane anesthesia.

PMID- 29176299
TI  - Effects of calcium-containing desensitizers on the bonding stability of an etch
      and-rinse adhesive against long-term water storage and pH cycling.
AB  - This study aimed to evaluate the effects of two calcium-containing desensitizing
      pastes on the bonding stability of an etch-and-rinse (E&R) adhesive to dentine.
      After dentine hypersensitivity model established, dentine surfaces were assigned
      one of the following pretreatment: Group 1, no desensitizer; Group 2, CPP-ACP;
      and Group 3, Novamin. Specimens were then bonded with an E&R adhesive. Beams from
      each tooth were randomly divided into three subgroups and then subjected to
      microtensile bond strength (MTBS) test after 24 h; 12 months of water storage; or
      15 runs of pH cycling. Failure modes, nanoleakage, and tubule-occluding
      effectiveness were analyzed. Results showed that CPP-ACP- or Novamin-pretreated
      specimens mainly preserved the bonding strength after 12 months of water storage,
      while effective tubule occlusion could be observed. The results suggested that
      the calcium-containing desensitizers were compatible pretreatment for bonding
      with E&R adhesives to obtain reliable long-term bonding strength and prevention
      of post-operative sensitivity.

PMID- 29176300
TI  - Effect of doxycycline-treated hydroxyapatite surface on bone apposition: A
      histomophometric study in murine maxillae.
AB  - Improved osseointegration of dental implants is imperative in clinic. Effect of
      doxycycline on promoting bone formation after implant placement was expected due
      to its inhibitory properties on inflammation and osteoclastogenesis. To evaluate
      new bone formation on the hydroxyapatite (HA)-coated implant surface, which was
      treated with doxycycline, in comparison with the untreated HA surface, half of
      the HA-coated implants were soaked in doxycycline solution (DOX group) whereas
      the other HA-coated implants were untreated (HA group). Eight weeks after
      extracting the maxillary first molars of 4-week-old male mice, the implants of
      both groups were placed at the extracted site. 4 and 8 weeks after surgery, the
      samples were evaluated radiologically and histomorphometrically. Bone-implant
      contact of DOX group was statistically higher than the one of HA group at 4 and 8
      weeks. New bone area between the threads of the implants also statistically
      increased at 8 weeks in DOX group compared to HA group.

PMID- 29176301
TI  - A novel cold atmospheric pressure air plasma jet for peri-implantitis treatment:
      An in vitro study.
AB  - Peri-implantitis is difficult to treat in clinical settings; this is not only
      because it is a site-specific infectious disease but also because it impedes
      osseointegration. In this study, a novel cold atmospheric pressure air plasma jet
      (CAPAJ) was applied to study the treatment of peri-implantitis in vitro. CAPAJ
      treated the samples for 2, 4 and 6 min, respectively. To evaluate the titanium
      surface characteristics, the surface elemental composition (X-ray photoelectron
      spectroscopy [XPS]), roughness and hydrophilicity were evaluated in each group.
      Concurrently, the sterilization and osseointegration effect of CAPAJ were also
      examined. Results revealed that after CAPAJ modification, roughness and
      hydrophilicity of titanium surfaces were significantly increased. Moreover, XPS
      results demonstrated that the C1s peak was reduced and N1s and O1s peaks were
      obviously improved. More importantly, CAPAJ showed favorable sterilization and
      bone formation effects. CAPAJ seemed a simpler and more efficient strategy for
      the peri-implantitis treatment.

PMID- 29176302
TI  - Influence of increment thickness on radiant energy and microhardness of bulk-fill
      resin composites.
AB  - Determining the energy transferred at the bottom of eleven bulk-fill resin
      composites, comparing top and bottom microhardness's and evaluating the
      correlation between microhardness and radiant energy were aimed. Samples were
      placed over the bottom sensor of a visible light transmission spectrophotometer
      and polymerized for 20 s. The bottom and top Knoop microhardness were measured.
      Paired t-test and correlation analysis were used for statistics (p<=0.05). In all
      groups, the bottom radiant energy decreased significantly with increasing
      thickness. For groups of Aura 2 mm, X-tra Fil 2 and 4 mm, SDR 2 and 4 mm, X-tra
      Base 2 mm no significant difference was found between top and bottom
      microhardness. For the bottom levels of Aura, X-tra Fil, Filtek Bulk-Fill
      Posterior, SDR, X-tra Base groups no significant difference was found between the
      microhardness's of 2 and 4 mm thicknesses. For X-tra Fil, Tetric Evo Ceram Bulk
      Fill, Filtek Bulk-Fill Flowable and Z100 groups radiant energy affected
      positively the microhardness.

PMID- 29176303
TI  - Comparison of enamel bond fatigue durability between universal adhesives and two
      step self-etch adhesives: Effect of phosphoric acid pre-etching.
AB  - The effect of phosphoric acid pre-etching on enamel bond fatigue durability of
      universal adhesives and two-step self-etch adhesives was investigated. Four
      universal adhesives and three two-step self-etch adhesives were used. The initial
      shear bond strengths and shear fatigue strengths to enamel with and without
      phosphoric acid pre-etching using the adhesives were determined. SEM observations
      were also conducted. Phosphoric acid pre-etching of enamel was found to increase
      the bond fatigue durability of universal adhesives, but its effect on two-step
      self-etch adhesives was material-dependent. In addition, some universal adhesives
      with phosphoric acid pre-etching showed similar bond fatigue durability to the
      two-step self-etch adhesives, although the bond fatigue durability of universal
      adhesives in self-etch mode was lower than that of the two-step self-etch
      adhesives. Phosphoric acid pre-etching enhances enamel bond fatigue durability of
      universal adhesives, but the effect of phosphoric acid pre-etching on the bond
      fatigue durability of two-step self-etch adhesives was material-dependent.

PMID- 29176304
TI  - Dual function of proanthocyanidins as both MMP inhibitor and crosslinker in
      dentin biomodification: A literature review.
AB  - Proanthocyanidin, a natural phytochemical bioactive agent, simultaneously can
      silence the activity of dentinal proteases and crosslink the collagen matrix;
      both of these phenomena would be the fundamentals for bio-stability of resin
      dentin interface which is essential for a promising adhesive dentistry. This
      review provides an overview of the data developed by different groups of
      researchers and highlighted topics are proanthocyanidin chemistry, natural
      resources and the unique interactions between proanthocyanidincollagen and
      proanthocyanidin-MMPs in dentin. Besides, clinical applications of
      proanthocyanidin in the form of proanthocyanidin-containing adhesives,
      preconditioners and etchants have been reviewed. One hundred and twelve studies
      have been published in peer-reviewed journals from 1981 to 2017, all were
      comprised in this review, some of them have been actually proven to be promising
      from clinical point of view and others need further assessment before their
      adoption as clinically practicable protocols.

PMID- 29176305
TI  - Correlations between fracture load of zirconia implant supported single crowns
      and mechanical properties of restorative material and cement.
AB  - Zirconia implants that were restored with veneered zirconia displayed severe
      chipping rates of the restorations in clinical studies. Purpose of this study was
      to evaluate the fracture load of different zirconia implant supported monolithic
      crown materials (zirconia, alumina, lithium disilicate, feldspar ceramic and
      polymer-infiltrated ceramic) cemented with various cements (Harvard LuteCem SE,
      Harvard Implant Semi-permanent, Multilink Automix, VITA Adiva F-Cem). Flexural
      strength and fracture toughness of crown materials and compressive strength of
      the cements were measured. Fracture load values of crowns fabricated from lithium
      disilicate, feldspar ceramic and polymer-infiltrated ceramic were increased when
      cement with high compressive strength was used. Fracture loads for zirconia and
      alumina crowns were not influenced by the cement. Flexural strength and fracture
      toughness of the ceramics correlated linearly with the respective fracture load
      when using adhesive cement with high compressive strength. To achieve sufficient
      fracture load values, cementation with adhesive cement is essential for feldspar
      and polymer-infiltrated ceramic.

PMID- 29176306
TI  - Nitrogen Fixation Genes and Nitrogenase Activity of the Non-Heterocystous
      Cyanobacterium Thermoleptolyngbya sp. O-77.
AB  - Cyanobacteria are widely distributed in marine, aquatic, and terrestrial
      ecosystems, and play an important role in the global nitrogen cycle. In the
      present study, we examined the genome sequence of the thermophilic non
      heterocystous N2-fixing cyanobacterium, Thermoleptolyngbya sp. O-77 (formerly
      known as Leptolyngbya sp. O-77) and characterized its nitrogenase activity. The
      genome of this cyanobacterial strain O-77 consists of a single chromosome
      containing a nitrogen fixation gene cluster. A phylogenetic analysis indicated
      that the NifH amino acid sequence from strain O-77 was clustered with those from
      a group of mesophilic species: the highest identity was found in Leptolyngbya sp.
      KIOST-1 (97.9% sequence identity). The nitrogenase activity of O-77 cells was
      dependent on illumination, whereas a high intensity of light of 40 MUmol m-2 s-1
      suppressed the effects of illumination.

PMID- 29176310
TI  - Urinary Disorders and Marfan Syndrome: A Series of 4 Cases.
AB  - Marfan syndrome is a genetic disease responsible for causing cardiovascular, eye
      and musculoskeletal damages. Urinary disorders are not common. We present 4 cases
      of chronic urinary tract symptoms, with 2 different pathophysiological processes.
      Three patients presented with spinal cord infarct following aortic dissection
      surgery. They were affected by an overactive bladder with detrusor overactivity
      and detrusor-sphincter dyssynergia. One patient complained of voiding
      dysfunction, possibly related to dural ectasia. Although a rare outcome, urinary
      disorders may appear in Marfan syndrome, by the occurrence of surgical
      complications in aortic surgery or possibility of sacral nerve root compression.
      If so, medical care is necessary to prevent uro-nephrological complications.

PMID- 29176311
TI  - Effect of Magnesium on Glomerular Filtration Rate and Recovery of Hypertension in
      Women with Severe Preeclampsia.
AB  - INTRODUCTION: Magnesium sulfate is used for preventing seizures in patients with
      severe preeclampsia. Previous studies have demonstrated that magnesium plays a
      significant role in the endothelial function and might have clinically beneficial
      vasodilating properties. OBJECTIVES: This study is aimed at evaluating the effect
      of magnesium sulfate on the glomerular filtration rate (GFR) during the first 24
      h after delivery and during the duration of recovery from hypertension in
      preeclampsia. METHODS: Severe preeclamptic patients who had normal serum
      creatinine levels (0.4-0.8 mg/dL) were included in the study. Twenty-three women
      with severe preeclampsia were divided into groups of 9, 8, and 6, and given 1.0,
      1.5, and 2.0 g/h of magnesium sulfate, respectively. Magnesium sulfate infusion
      was used as seizure prophylaxis for 24 h after delivery. The cystatin C-based GFR
      was monitored for 24 h, and the blood pressure was recorded for 12 weeks
      postpartum. RESULTS: Despite the minimal improvement of GFR 24-h after treatment
      initiation, survival analysis demonstrated a statistically significant
      relationship (log rank, p = 0.04) between magnesium dosage and recovery period
      from hypertension. The group receiving 2.0 g/h of magnesium experienced the
      shortest recovery period from hypertension (6.5 +/- 1.8 days). Meanwhile, the
      other groups required 66.0 +/- 26.9 and 48.3 +/- 15.6 days to recover after 1.0
      and 1.5 g/h of magnesium infusion, respectively. CONCLUSION: Magnesium sulfate
      has no impact on GFR improvement during the first 24 h after delivery. However,
      magnesium maintenance infusion at 2.0 g/h is capable of preventing seizure by
      optimizing the therapeutic magnesium level (4.8-8.4 mg/dL) and shortening the
      hypertensive episode in preeclampsia.

PMID- 29176312
TI  - Validation of a Paediatric Speech and Language Screening (RALF).
AB  - BACKGROUND/AIMS: This study aims to analyse psychometric characteristics of the
      Portuguese Paediatric Speech and Language Screening (RALF) test. METHODS: 202
      Portuguese children aged 3; 0-5; 11 were recruited from 4 kindergartens
      participating in this study. Reliability and validity (sensitivity and
      specificity) data were obtained and analysed. RESULTS: Content validity, analysed
      by an expert panel (general practitioner, kindergarten, teacher, nurse, and
      speech and language pathologist) revealed that the items were representative and
      relevant for the content the instrument intends to measure. Sensitivity values
      were 95, 96, and 83% and specificity values were 85, 84, and 71% for the age
      groups 3; 0-3; 11, 4; 0-4; 11, and 5; 0-5; 11, respectively. Internal
      consistency, calculated through Cronbach's alpha, was 0.7, 0.8, and 0.7,
      respectively. The inter-judge reliability (interclass correlation coefficient)
      was 0.951. The results ensure the content validity of RALF. Sensitivity and
      specificity values revealed that RALF could discriminate typical from disordered
      speech-language developing children. RALF also presented good internal
      consistency and excellent reliability. CONCLUSION: RALF is a reliable and valid
      screening instrument that health and educational professionals can use in
      Portuguese children to identify children who may need a speech-language diagnosis
      for consideration or referral to speech therapy services.

PMID- 29176313
TI  - Acute Kidney Injury Following Acute Ischemic Stroke and Intracerebral Hemorrhage:
      A Meta-Analysis of Prevalence Rate and Mortality Risk.
AB  - BACKGROUND: The epidemiology of acute renal dysfunction after stroke is routinely
      overlooked following stroke events. Our aim in this meta-analysis is to report
      the prevalence of acute kidney injury (AKI) following acute stroke and its impact
      on mortality. METHODS: A systematic literature search was performed on PubMed,
      EMBASE and Google Scholar for observational studies examining the prevalence and
      mortality risk of stroke patients with AKI as a complication. The pooled
      prevalence rates and odds ratios for mortality risk were calculated using
      subgroup analyses between the stroke subtypes: acute ischemic stroke (AIS) and
      intracerebral hemorrhage (ICH). RESULTS: A total of 12 studies (4,532,181 AIS and
      615,636 ICH) were included. The pooled prevalence rate of AKI after all stroke
      types was 11.6% (95% CI 10.6-12.7). Subgroup analyses revealed that the pooled
      prevalence rate of AKI after AIS was greater but not statistically significantly
      different than ICH (19.0%; 95% CI 8.2-29.7 vs. 12.9%; 95% CI 10.3-15.5, p = 0.5).
      AKI was found to be a significant risk factor of mortality in AIS (adjusted OR
      [aOR] 2.23; 95% CI 1.28-3.89; I2 = 98.8%), whereas this relationship did not
      reach statistical significance in ICH (aOR 1.20; 95% CI 0.68-2.12; I2 = 74.2%).
      CONCLUSIONS: This meta-analysis provides evidence that AKI is a common
      complication following both AIS and ICH and it is associated with increased
      mortality following AIS but not ICH. This highlights the need for early
      assessment of renal function in the acute phase of AIS, in particular, and
      avoidance of factors than may induce AKI in vulnerable patients.

PMID- 29176314
TI  - Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and
      Metastasis through PI3K/AKT/GSK-3beta Signalling in Oral Squamous Cell Carcinoma.
AB  - BACKGROUND/AIMS: Zinc finger protein 703 (ZNF703), initially identified as a
      novel oncogene in human breast cancer, is a member of the NET/NlZ family of zinc
      finger transcription factors. It is recognized that the overexpression of ZNF703
      is associated with various types of human cancers, but the role and molecular
      mechanism of ZNF703 in oral squamous cell carcinoma (OSCC) are unknown. METHODS:
      ZNF703 expression levels were examined in OSCC tissues and non-cancerous tissues
      by qRT-PCR and immunohistochemistry (IHC). The molecular mechanisms of ZNF703 and
      its effects on cell growth and metastasis were explored in vitro and in vivo
      using the CCK8 assay, colony formation assay, cell cycle analysis, migration and
      invasion assays, wound-healing assay, western blotting and xenograft experiments
      in nude mice. RESULTS: In this study, ZNF703 was found to be upregulated in OSCC
      tissues compared to that in normal tissues at both mRNA and protein levels, and
      its expression level was closely correlated with the overall survival of patients
      with OSCC. Silencing of the ZNF703 gene in OSCC cells significantly inhibited
      cell growth and metastasis in vitro and in vivo. Conversely, the overexpression
      of ZNF703 in OSCC cells promoted cancer growth and metastasis in vitro.
      Mechanistically, ZNF703 activated the PI3K/AKT/GSK-3beta signalling pathway and
      its downstream effectors, thus regulating the cell cycle and epithelial
      mesenchymal transition (EMT). Furthermore, the promotive effects of ZNF703 on
      cellular proliferation and metastasis could be rescued by LY294002 (a PI3K
      specific inhibitor) and MK2206 (an Akt-specific inhibitor). CONCLUSION: The
      results show that ZNF703 promotes cell growth and metastasis through PI3K/Akt/GSK
      3beta signalling in OSCC and that it may be a promising target in the treatment
      of patients with OSCC.

PMID- 29176315
TI  - Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder
      Outlet Obstruction.
AB  - BACKGROUND/AIMS: Overactive bladder associated with bladder outlet obstruction
      (BOO) is a highly prevalent condition, which is usually treated with
      antimuscarinics. However, the potential effects of antimuscarinics on the
      structure and function of bladder have not been investigated thus far. METHODS:
      Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery,
      and then received treatment of three different antimuscarinics (Solifenacin,
      Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder
      function and structure were measured. The effect of antimuscarinics on cellular
      alteration in vitro was observed under mechanical stimulation. Bladder morphology
      were examined by immunohistochemistry, and the bladder function were investigated
      by cystometry and strip contractility test. The expression of muscarinic
      receptors and inflammatory cytokines were measured by PCR and Western blotting.
      RESULTS: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are
      protective regulators for the bladder structure and function. Antimuscarinics
      decrease the weight of bladders with BOO. Antimuscarinics improve the voiding
      parameter and enhance the contraction of bladder smooth muscle. The results also
      show that antimuscarinics inhibit the proliferation of bladder smooth muscle
      cells both in vivo and in vitro, it can reduce the collagen deposition and
      inflammatory cytokines in bladders with BOO. During this process, the expression
      of M2 and M3 receptors was altered by antimuscarinics. CONCLUSION:
      Antimuscarinics could reverse the structural and functional changes of BOO
      bladder wall at cellular and tissue level, and the alteration of M2 and M3
      receptors may be involved in this biological process.

PMID- 29176316
TI  - Toward Using a Smartwatch to Monitor Frailty in a Hospital Setting: Using a
      Single Wrist-Wearable Sensor to Assess Frailty in Bedbound Inpatients.
AB  - BACKGROUND: While various objective tools have been validated for assessing
      physical frailty in the geriatric population, these are often unsuitable for busy
      clinics and mobility-impaired patients. Recently, we have developed a frailty
      meter (FM) using two wearable sensors, which allows capturing key frailty
      phenotypes (weakness, slowness, and exhaustion), by testing 20-s rapid elbow
      flexion-extension test. OBJECTIVE: In this study, we proposed an enhanced
      automated algorithm to identify frailty using a single wrist-worn sensor.
      METHODS: The data collected from 100 geriatric inpatients (age: 78.9 +/- 9.1
      years, 49% frail) were reanalyzed to validate the new algorithm. The frailty
      status of the participants was determined using a validated modified frailty
      index. Different FM phenotypes (31 features) including velocity of elbow
      rotation, decline in velocity of elbow rotation over 20 s, range of motion, etc.
      were extracted. A regression model, bootstrap with 2,000 iterations, and
      recursive feature elimination technique were used for optimizing the FM
      parameters and identifying frailty using a single wrist-worn sensor. RESULTS: A
      strong agreement was observed between two-sensor and wrist-worn sensor
      configuration (r = 0.87, p < 0.001). Results suggest that the wrist-worn FM with
      no demographic information still yields a high accuracy of 80.0% (95% CI: 79.7
      80.3%) and an area under the curve of 87.7% (95% CI: 87.4-87.9%) to identify
      frailty status. Results are comparable with two-sensor configuration, where the
      observed accuracy and area under the curve were 80.6% (95% CI: 80.4-80.9%) and
      87.4% (95% CI: 87.1-87.6%), respectively. CONCLUSION: The simplicity of FM may
      open new avenues to integrate wearable technology and mobile health to capture
      frailty status in a busy hospital setting. Furthermore, the reduction of needed
      sensors to a single wrist-worn sensor allows deployment of the proposed algorithm
      in the form of a smartwatch application. From the application standpoint, the
      proposed FM is superior to traditional physical frailty-screening tools in which
      the walking test is a key frailty phenotype, and thus they cannot be used for
      bedbound patients or in busy clinics where administration of gait test as a part
      of routine assessment is impractical.

PMID- 29176317
TI  - Downregulated MicroRNA-195 in the Bicuspid Aortic Valve Promotes Calcification of
      Valve Interstitial Cells via Targeting SMAD7.
AB  - BACKGROUND/AIMS: Aortic stenosis caused by leaflet calcification in the bicuspid
      aortic valve (BAV) is more accelerative than that in the tricuspid aortic valve
      (TAV). MicroRNA-195 (miR-195) is downregulated more in stenotic than in
      insufficient BAVs, but its expression in BAVs compared with TAVs is unclear. We
      aimed to investigate the roles of miR-195 and its calcification-related target
      SMAD7 in stenotic BAVs compared with those in TAVs. METHODS: Twenty-one stenotic
      BAV and 29 TAV samples were collected from surgical patients and examined for the
      expression of miR-195 and SMAD7 by RT-PCR. The samples were also assessed by
      western blotting and immunohistochemistry for the functional protein alteration
      associated with calcification. Dual-luciferase assay was performed to determine
      the putative target of miR-195 before the effects of miR-195 expression on
      osteogenic progression was demonstrated in cultured porcine valve interstitial
      cells (VICs). RESULTS: Compared with TAV, the expression of miR-195 was
      remarkably lower in the BAV leaflet with higher expression of SMAD7, which was
      then validated as a direct target of miR-195. Their negative correlation was then
      confirmed in cultured VICs. Under an osteogenic environment, the cellular
      calcification was promoted in miR-195-repressed VICs expressing higher BMP-2 and
      Runx2 and higher activity of MMP-2 compared with the controls. Finally, higher
      MMP-2 and MMP-9 expression and more collagen distribution were observed in BAV
      than TAV samples. CONCLUSIONS: miR-195 is downregulated more in stenotic BAV than
      TAV in this study. The downregulation of miR-195 is associated with valvular
      calcification via targeting SMAD7, which promotes the remodeling of the
      extracellular matrix.

PMID- 29176319
TI  - E3 Ubiquitin Ligase RNF125 Activates Interleukin-36 Receptor Signaling and
      Contributes to Its Turnover.
AB  - Signaling by the interleukin-36 receptor (IL-36R) is linked to inflammatory
      diseases such as psoriasis. However, the regulation of IL-36R signaling is poorly
      understood. Activation of IL-36R signaling in cultured cells results in an
      increased polyubiquitination of the receptor subunit, IL-1Rrp2. Treatment with
      deubiquitinases shows that the receptor subunit of IL-36R, IL-1Rrp2, is primarily
      polyubiquitinated at the K63 position, which is associated with endocytic
      trafficking and signal transduction. A minor amount of ubiquitination is at the
      K48 position that is associated with protein degradation. A focused siRNA screen
      identified RNF125, an E3 ubiquitin ligase, to ubiquitinate IL-1Rrp2 upon
      activation of IL-36R signaling while not affecting the activated IL-1 receptor.
      Knockdown of RNF125 decreases signal transduction by the IL-36R. Overexpression
      of RNF125 in HEK293T cells activates IL-36R signaling and increases the
      ubiquitination of IL-1Rrp2 and its subsequent turnover. RNF125 can
      coimmunoprecipitate with the IL-36R, and it traffics with IL-1Rrp2 from the cell
      surface to lysosomes. Mutations of Lys568 and Lys569 in the C-terminal tail of IL
      1Rrp2 decrease ubiquitination by RNF125 and increase the steady-state levels of
      IL-1Rrp2. These results demonstrate that RNF125 has multiple regulatory roles in
      the signaling, trafficking, and turnover of the IL-36R.

PMID- 29176318
TI  - CCL2 is Upregulated by Decreased miR-122 Expression in Iron-Overload-Induced
      Hepatic Inflammation.
AB  - BACKGROUND/AIMS: Iron overload (IO) is accompanied by hepatic inflammation. The
      chemokine (C-C motif) ligand 2 (CCL2) mediates inflammation, and its
      overexpression is associated with IO. However, whether IO results in CCL2
      overexpression in the liver and the underlying mechanisms are unclear. METHODS:
      We subjected mice to IO by administering intraperitoneal injections of dextran
      iron or by feeding mice a 3% dextran-iron diet to observe the effects of IO on
      miR-122/CCL2 expression through real-time qPCR and Western blot analysis. We also
      used indicators, including the expression of the inflammatory cytokine, the
      inflammation score based on H&E staining and the serum content of ALT and AST to
      evaluate the effects of IO on hepatic inflammation. Meanwhile, we observed the
      effects of vitamin E on IO-induced hepatic inflammation. In cells, we used 100
      uMU FeSO4 or 30 uMU Holo-Tf to produce IO and observed the roles of miR-122 in
      regulating CCL2 expression by using miR-122 mimics or inhibitors to overexpress
      or inhibit miR-122. Then, we used a dual-luciferase reporter assay to prove that
      miR-122 regulates CCL2 expression through direct binding to its complementary
      sequence in the CCL2 mRNA 3'UTR. RESULTS: IO induces the downregulation of miR
      122 and the upregulation of CCL2, as well as inflammatory responses both in vitro
      and in vivo. Although IO-induced oxidative stress is eliminated by the
      antioxidant vitamin E, IO-induced hepatic inflammation still exists, which
      probably can be explained by the fact that vitamin E has no effects on the miR
      122/CCL2 pathway. In in vitro experiments, the overexpression and inhibition of
      miR-122 significantly reduced and increased CCL2 expression, respectively. The
      dual-luciferase reporter assay indicates that miR-122 binds CCL2 mRNA 3'UTR.
      CONCLUSION: We propose the roles of miR-122/CCL2 in IO-induced hepatic
      inflammation. Our studies should provide a new clue for developing clinical
      strategies for patients with IO.

PMID- 29176320
TI  - The Dual Regulatory Role of MiR-181a in Breast Cancer.
AB  - MicroRNAs (miRNAs) are a family of highly conserved noncoding single-stranded RNA
      molecules of 21 to 25 nucleotides. miRNAs silence their cognate target genes at
      the post-transcriptional level and have been shown to have important roles in
      oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene
      regulation. Recent evidence indicates that the expression of miR-181a is altered
      in breast tumor tissue and in the serum of patients with breast cancer. However,
      there are several contradicting findings that challenge the biological
      significance of miR-181a in tumor development and metastasis. In fact, some
      studies have implicated miR-181a in regulating breast cancer gene expression.
      Here we summarize the current literature demonstrating established links between
      miR-181a and human breast cancer with a focus on recently identified mechanisms
      of action. This review also aims to explore the potential of miR-181a as a
      diagnostic and/or prognostic biomarker for breast cancer and to discuss the
      contradicting data regarding its targeting therapeutics and the associated
      challenges.

PMID- 29176321
TI  - Clinical Characteristics and Prognostic Factors of Small Intestine Angiosarcoma:
      a Retrospective Clinical Analysis of 66 Cases.
AB  - BACKGROUND/AIMS: Primary angiosarcoma of the small intestine is a rare neoplasia,
      and there are limited data from systematic analyses. The aim of this study is to
      describe the clinical and pathological characteristics in addition to the
      prognostic factors for this rare neoplasia. METHODS: We retrospectively collected
      the clinical records and prognostic information of 66 patients with small
      intestine angiosarcoma reported between 1970 and 2017. We used the Chi-square
      test, the log-rank test, and Cox regression analyses to evaluate the data.
      RESULTS: There were 66 patients diagnosed with small intestine angiosarcoma. The
      onset age ranged from 24-92 years old. There were 24 patients diagnosed before
      the year 2000, and 42 patients were diagnosed after 2000. The data indicated that
      49 cases were diagnosed as primary disease, and the remaining 15 cases were
      secondary disease. The main clinical symptoms were nonspecific and included
      gastrointestinal (GI) bleeding and abdominal pain. Additionally, we found multi
      center foci were one of the characteristics of this disease. Radiation-induced
      small intestine angiosarcoma (RSIA) is a special type of disease with a similar
      prognosis. This type was more frequent in females and decreased after the year
      2000. We also found that GI bleeding was less common in RSIA cases. The log-rank
      test results revealed that old-age, poor differentiation, and GI bleeding were
      associated with worse prognosis. Surgical treatment showed a trend toward a
      prolonged survival time. However, the result was not statistically significant.
      Our results show treatment with adjuvant therapy improved prognosis. The
      multivariate Cox analysis demonstrated adjuvant therapy was an independent
      indicator of a favorable outcome in small intestine angiosarcoma patients.
      CONCLUSION: Pay attention to the unexplained gastrointestinal bleeding could lead
      to a faster diagnosis and control of small intestine angiosarcoma. Furthermore,
      treatments including adjuvant therapy can effectively improve the prognosis.

PMID- 29176322
TI  - Differential Expression Profiles of the Transcriptome in Breast Cancer Cell Lines
      Revealed by Next Generation Sequencing.
AB  - BACKGROUND/AIMS: As MCF-7 and MDA-MB-231 cells are the typical cell lines of two
      clinical breast tumour subtypes, the aim of the present study was to elucidate
      the transcriptome differences between MCF-7 and MDA-MB-231 breast cancer cell
      lines. METHODS: The mRNA, miRNA (MicroRNA) and lncRNA (Long non-coding RNA)
      expression profiles were examined using NGS (next generation sequencing)
      instrument Illumina HiSeq-2500. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia
      of Genes and Genomes) pathway analyses were performed to identify the biological
      functions of differentially expressed coding RNAs. Subsequently, we constructed
      an mRNA-ncRNA (non-coding RNA) targeting regulatory network. Finally, we
      performed RT-qPCR (real-time quantitative PCR) to confirm the NGS results.
      RESULTS: There are sharp distinctions of the coding and non-coding RNA profiles
      between MCF-7 and MDA-MB-231 cell lines. Among the mRNAs and ncRNAs with the most
      differential expression, SLPI, SOD2, miR-7, miR-143 and miR-145 were highly
      expressed in MCF-7 cells, while CD55, KRT17, miR-21, miR-10b, miR-9, NEAT1 and
      PICSAR were over-expressed in MDA-MB-231 cells. Differentially expressed mRNAs
      are primarily involved in biological processes of locomotion, biological
      adhesion, ECM-receptor interaction pathway and focal adhesion. In the targeting
      regulatory network of differentially expressed RNAs, mRNAs and miRNAs are
      primarily associated with tumour metastasis, but the functions of lncRNAs remain
      uncharacterized. CONCLUSION: These results provide a basis for future studies of
      breast cancer metastasis and drug resistance.

PMID- 29176323
TI  - MiR-148b, MiR-152/ALCAM Axis Regulates the Proliferation and Invasion of
      Pituitary Adenomas Cells.
AB  - BACKGROUND/AIMS: Aberrant expression of miRNA has been found in many tumor
      tissues to regulate the tumorigenesis by binding to the 3'- untranslated region
      (3'-UTR) of the target genes. The aim of this study is to investigate the role of
      miR-148b, miR-152/ALCAM axis in human pituitary adenomas (PAs). METHODS: First,
      we detected the expression level of miR-148b-3p and miR-152 in human PAs samples
      by using qRT-PCR. Then we studied the role of miR-148b-3p, miR-152 on human PAs
      cell proliferation, invasion and apoptosis by using MTS assay, Transwell invasion
      assay and Annexin V/PI Staining Test. To study the relationship between miR-148b
      3p, miR-152 and activated leukocyte antigen molecule (ALCAM), we overexpressed
      miR-148-3p or miR-152 by transfecting specific mimics. Lucifearase reporter assay
      was then performed to confirm the target. Next, we studied the biological
      functions of ALCAM in human PAs cells. Finally, the role of miR-148b-3p, miR
      152/ALCAM axis in PAs cells was studied. RESULTS: The expression level of miR-148
      3p and miR-152 in invasive PAs samples was lower than those in noninvasive
      samples. Overexpression of miR-148b-3p, miR-152 could repress proliferation and
      invasion, and promote apoptosis. Moreover, miR-148b-3p and miR-152 could repress
      activated leukocyte antigen molecule (ALCAM) expression. Knockdown of ALCAM could
      repress proliferation and invasion and promote apoptosis. By contrary,
      overexpression of ALCAM promoted proliferation and invasion. Further, the rescue
      experiments indicated that overexpression of ALCAM significantly restored the
      proliferation, apoptosis, and invasion influenced by miR-148b-3p and miR-152.
      CONCLUSIONS: Our study suggests that miR-148b-3p, miR-152 may serve as
      suppressors in PAs through downregulating ALCAM expression. miR-148b, miR-152/
      ALCAM axis may be a new therapeutic target in the future.

PMID- 29176324
TI  - Pituitary Dysfunction in Pediatric Patients with Optic Nerve Hypoplasia: A
      Retrospective Cohort Study (1975-2014).
AB  - BACKGROUND/AIMS: The risk factors for pituitary hormone dysfunction (PHD) in
      children with optic nerve hypoplasia (ONH) are not well understood. This study
      identified the type, timing, and predictors of PHD in children with ONH. METHODS:
      ONH patient charts were reviewed retrospectively. The incidence rate of PHD was
      calculated assuming a Poisson distribution. Predictors of PHD were identified
      through a multivariable Cox proportional hazards model. RESULTS: Among 144
      subjects with ONH, 49.3% (n = 71) developed PHD over 614.7 person-years of follow
      up. The incidence was 11.55 (95% confidence interval [CI]: 9.02-14.57/100 person
      years). The median time to first PHD was 2.88 (interquartile range: 0.02-18.72)
      months. Eighty-two percent developed their first PHD by their 5th and 90% by
      their 10th birthday, and 89% within 5 years of ONH diagnosis. Prematurity
      (adjusted hazard ratio [aHR]: 0.33; 95% CI: 0.1-1.07), blindness (aHR: 1.72; 95%
      CI: 1.03-2.86), maternal substance abuse (aHR: 1.51; 95% CI: 0.91-2.48), abnormal
      posterior pituitary (aHR: 3.8; 95% CI: 2.01-7.18), and hypoplastic/absent
      anterior pituitary (aHR: 2.52; 95% CI: 1.29-4.91) were significant predictors of
      PHD. CONCLUSIONS: The clinical predictors of PHD included blindness, pituitary
      gland abnormalities, and maternal substance abuse. These predictors help clinical
      decision-making related to the need for and frequency of hormone testing in
      pediatric patients with ONH.

PMID- 29176325
TI  - Cav2.3 (R-Type) Calcium Channels are Critical for Mediating Anticonvulsive and
      Neuroprotective Properties of Lamotrigine In Vivo.
AB  - BACKGROUND/AIMS: Lamotrigine (LTG) is a popular modern antiepileptic drug (AED),
      however, its mechanism of action has yet to be fully understood, as it is known
      to modulate many members of several ion channel families. In heterologous
      systems, LTG inhibits Cav2.3 (R-type) calcium currents, which contribute to
      kainic-acid- (KA) induced epilepsy in vivo. To gain insight into the role of R
      type currents in LTG drug action in vivo, we compared the effects of LTG to
      topiramate and lacosamide in Cav2.3-deficient mice and controls on KA-induced
      seizures. METHODS: Behavioral seizure rating and quantitative
      electrocorticography were performed after injection of 20 mg/kg [and 30 mg/kg]
      KA. One hour before KA injection, mice were pretreated with either 30 mg/kg LTG,
      50 mg/kg topiramate (TPM) or 30 mg/kg lacosamide (LSM). RESULTS: Ablation of
      Cav2.3 reduced total seizure scores by 28.6% (p=0.0012) and pretreatment with LTG
      reduced seizure activity of control mice by 23.2% (p=0.02). In Cav2.3-deficient
      mice LTG pretreatment increased seizure activity by 22.1% (p=0.018) and increased
      the percentage of degenerated CA1 pyramidal neurons (p=0.02). All three tested
      AEDs reduced seizure activity in control mice, however only the non-calcium
      channel modulating AED, LSM had an anticonvulsive effect in Cav2.3-deficient
      mice. Furthermore LTG altered electrocorticographic parameters differently in the
      two genotypes, decreasing relative power of ictal spikes in control mice compared
      to Cav2.3-defcient mice. CONCLUSION: These findings give first in vivo evidence
      for an essential role for Cav2.3 in LTG pharmacology and shed light on a
      paradoxical effect of LTG in their absence. Furthermore, LTG appears to promote
      ictal activity in Cav2.3-deficient mice resulting in increased neurotoxicity in
      the CA1 region. This paradoxical mechanism, possibly reflecting rebound
      hyperexcitation of pyramidal CA1 neurons after increased inhibition, may be key
      in understanding LTG-induced seizure aggravation, observed in clinical practice.

PMID- 29176326
TI  - High Systolic Blood Pressure after Successful Endovascular Treatment Affects
      Early Functional Outcome in Acute Ischemic Stroke.
AB  - BACKGROUND: Endovascular treatment (EVT) has been shown to significantly improve
      functional outcome in patients with acute large cerebral vessel occlusions. To
      date, no evidence-based recommendations on blood pressure management after
      successful EVT exist. Previous studies showed an association between high pre-EVT
      systolic blood pressure (SBP) and functional outcome, but do not answer the
      question on how to manage blood pressure after successful recanalization. The
      purpose of this study was to determine the role of blood pressure measurements as
      a predictor for early functional outcome in patients with successful EVT.
      METHODS: Prospectively derived data from patients with acute large vessel
      occlusion within the anterior circulation and EVT was analyzed in this
      monocentric study. Mean systolic- and maximum SBP as well as SBP-peaks have been
      obtained for the first 24 h after successful EVT. Predictive value of SBP for
      discharge modified Rankin Scale (mRS) <=2 has been investigated using logistic
      regression models. RESULTS: From 168 patients with successful EVT, 74 (44%) had a
      favorable outcome with an mRS <=2. Mean- (127 vs. 131 mm Hg, p = 0.035) and
      maximum SBP (157 vs. 169 mm Hg, p < 0.001) as well as the number of SBP-peaks (0
      vs. 1.5, p = 0.004) were lower in patients with favorable outcomes. Multivariable
      logistic regression showed high mean- and maximum SBP to predict unfavorable
      outcomes. Cutoff mean SBP was 141 mm Hg and maximum SBP 159 mm Hg. CONCLUSIONS:
      High SBP in the first 24 h after recanalization of acute anterior cerebral vessel
      occlusions is associated with unfavorable functional outcome. Interventional
      studies are needed to determine the role of SBP management as a modifiable
      parameter in the early phase after successful EVT.

PMID- 29176327
TI  - Hyperkalemia Associated with Renin-Angiotensin-Aldosterone System Inhibition in
      Patients with Heart Failure; Underexplored and Overrated?

PMID- 29176328
TI  - Cardiomyopathy-Associated Gene 1-Sensitive PKC-Dependent Connexin 43 Expression
      and Phosphorylation in Left Ventricular Noncompaction Cardiomyopathy.
AB  - BACKGROUND/AIMS: Cardiomyopathy-associated gene 1 (CMYA1) plays an important role
      in embryonic cardiac development, postnatal cardiac remodeling and myocardial
      injury repair. Abnormal CMYA1 expression may be involved in cardiac dysplasia and
      primary cardiomyopathy. Our study aims to establish the relationship between
      CMYA1 and Left ventricular noncompaction cardiomyopathy (LVNC) pathogenesis.
      METHODS: We explored the effects of CMYA1 on connexins (Cx), which contribute to
      gap junction intercellular communication (GJIC), and the underlying signaling
      pathway in human normal tissues, LVNC myocardial tissues and HL1 cells by means
      of western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, co
      immunoprecipitation and scrape loading-dye transfer. RESULTS: CMYA1 expression
      was inversely associated with Cx43 and Cx40 expression, as determined by gap
      junction PCR array analysis. An increased expression and disordered distribution
      of CMYA1 at the intercalated discs in LVNC myocardial tissue was also observed.
      CMYA1 and Cx43 are co-expressed and interact in myocardial cells. CMYA1
      expression was positively correlated with p-Cx43 (S368) via the Protein kinase C
      (PKC) signaling pathway in myocardial tissue and HL1 cells. The diffusion
      distance of Lucifer Yellow in the HL1 cells in which CMYA1 was over-expressed or
      knocked down was significantly less or more than that of the control group,
      respectively. CONCLUSION: Abnormal CMYA1 expression affects the expression and
      phosphorylation of Cx43 through the PKC signaling pathway, which is involved in
      the regulation of GJIC. CMYA1 participates in the molecular mechanism of LVNC
      pathogenesis.

PMID- 29176329
TI  - Inflammatory processes during acute respiratory distress syndrome: a complex
      system.
AB  - PURPOSE OF REVIEW: ARDS is a severe pulmonary disease characterized by
      inflammation. However, inflammation-directed therapies have yet failed to improve
      the outcome in ARDS patients. One of the reasons may be the underestimated
      complexity of inflammation. Here, we summarize recent insights into the complex
      interrelations between inflammatory circuits. RECENT FINDINGS: Gene expression
      analysis from animal models or from patients with ARDS, sepsis or trauma show an
      enormous number of differentially expressed genes with highly significant
      overlaps between the various conditions. These similarities, however, should not
      obscure the complexity of inflammation. We suggest to consider inflammation in
      ARDS as a system controlled by scale-free networks of genome-wide molecular
      interaction with hubs (e.g. NFkappaB, C/EBPbeta, ATF3), exhibiting nonlinear
      emergence and the ability to adapt, meaning for instance that mild and life
      threatening inflammation in ARDS are distinct processes. In order to comprehend
      this complex system, it seems necessary to combine model-driven simulations, data
      driven modelling and hypothesis-driven experimental studies. Recent experimental
      studies have illustrated how several regulatory circuits interact during
      pulmonary inflammation, including the resolution of inflammation, the
      inflammasome, autophagy and apoptosis. SUMMARY: We suggest that therapeutic
      interventions in ARDS should be based on a systems approach to inflammation.

PMID- 29176330
TI  - Dissipation of energy during the respiratory cycle: conditional importance of
      ergotrauma to structural lung damage.
AB  - PURPOSE OF REVIEW: To describe and put into context recent conceptual advances
      regarding the relationship of energy load and power to ventilator-induced lung
      injury (VILI). RECENT FINDINGS: Investigative emphasis regarding VILI has almost
      exclusively centered on the static characteristics of the individual tidal cycle 
      tidal volume, plateau pressure, positive end-expiratory pressure, and driving
      pressure. Although those static characteristics of the tidal cycle are undeniably
      important, the 'dynamic' characteristics of ventilation must not be ignored. To
      inflict the nonrupturing damage we identify as VILI, work must be performed and
      energy expended by high stress cycles applied at rates that exceed the capacity
      of endogenous repair. Machine power, the pace at which the work performing energy
      load is applied by the ventilator, has received increasing scrutiny as a
      candidate for the proximate and integrative cause of VILI. SUMMARY: Although the
      unmodified values of machine-delivered energy or power (which are based on airway
      pressures and tidal volumes) cannot serve unconditionally as a rigid and
      quantitative guide to ventilator adjustment for lung protection, bedside
      consideration of the dynamics of ventilation and potential for ergotrauma
      represents a clear conceptual advance that complements the static parameters of
      the individual tidal cycle that with few exceptions have held our scientific
      attention.

PMID- 29176331
TI  - Management of work through the seasons of cancer survivorship.
AB  - PURPOSE OF REVIEW: Survival from cancer has expanded enormously over the past
      decades. It is estimated that 40-50% of all cancer survivors are of working age
      at time of diagnosis and thus potentially part of the labor force. The seasons of
      survivorship can be used as a steppingstone to describe issues regarding
      employability survivors are dealing with. RECENT FINDINGS: The acute survival
      stage begins at the point of diagnosis. Disclosure of diagnosis, and flexibility
      of both employers and (occupational) healthcare professionals are important
      factors in this stage. Extended survival starts when the survivor has completed
      the basic course of treatment. Survivors become aware that the old normality at
      work will be difficult to achieve. Problems like fear of recurrence, cognitive,
      and physical limitations might intensify during this stage and affect work
      ability. Permanent survival can be called long-term remission. Prospective
      studies on work-related outcomes and work-related interventions in this stage are
      rare. SUMMARY: It is important to improve our understanding of the seasons of
      survival and to explore concepts, such as employability, against the background
      of these seasons. This perspective may help both survivors and (occupational)
      healthcare professionals to develop better strategies for dealing with the
      difficult life event cancer represents in each specific stage.

PMID- 29176332
TI  - Transition to survivorship: can there be improvement?
AB  - PURPOSE OF REVIEW: The transition from primary cancer treatment to posttreatment
      follow-up care is seen as critical to the long-term health of survivors. However,
      relatively little attention has been paid to understanding this pivotal period.
      This review will offer a brief outline of the significant work surrounding this
      pivotal time published in the past year. RECENT FINDINGS: The growing number of
      cancer survivors has stimulated an emphasis on finding new models of care,
      whereby responsibility for survivorship follow-up is transitioned to primary care
      providers. A variety of models and tools have emerged for follow-up care.
      Survivorship care plans are heralded as a key component of survivorship care and
      a vehicle for supporting transition. Uptake of survivorship care plans and
      implementation of evidence-based models of survivorship care has been slow,
      hindered by a range of barriers. SUMMARY: Evaluation is needed regarding
      survivorship models in terms of feasibility, survivor friendliness, cost
      effectiveness, and achievement of sustainable outcomes. How, and when, to
      introduce plans for transition to the patient and determine transition readiness
      are important considerations but need to be informed by evidence. Additional
      study is needed to identify best practice for the introduction and application of
      survivorship care plans.

PMID- 29176333
TI  - Symptom cluster among patients with advanced heart failure: a review of its
      manifestations and impacts on health outcomes.
AB  - PURPOSE OF REVIEW: Assessment of symptom clustering is effective in enhancing
      care planning for symptom palliation in life-limiting disease. This review was
      aimed at identifying symptom cluster manifestation among advanced heart failure
      patients and to investigate the prognostic impact of the identified symptom
      clusters. RECENT FINDINGS: A systematic search of the literature identified 10
      relevant articles. Two approaches were undertaken based on: correlations between
      symptoms and shared characteristics of patients' symptom profiles, to identify
      the symptom clusters. By comparing the findings for heart failure patients at an
      advanced disease stage and those who were not, the symptom clusters of advanced
      heart failure were found to have unique characteristics. In particular, the
      typical symptoms associated with cardiac decompensation are not clustered
      together. Instead, dyspnoea is clustered with emotional symptoms indicating that
      a distressing dyspnoeic attack may reinforce awareness of the life-limiting
      nature of the disease and arouse negative emotions. In addition, the debilitating
      heart failure-specific symptoms share the cause of the life-limiting aspects in
      compromising patient vitality. The strong positive association between symptom
      burden and cardiac event prompts the need for effective intervention to palliate
      not only typical but also atypical and emotional symptoms of advanced heart
      failure. SUMMARY: This review provides insight on potentially effective
      interventions for symptom palliation in advanced heart failure.

PMID- 29176335
TI  - Acute Angle-closure Glaucoma as a First Presentation of Coats' Disease: A Case
      Report.
AB  - PURPOSE: The purpose of this study was to report an unusual first manifestation
      of Coats' disease presenting as an acute angle-closure glaucoma attack in an
      adult patient. PATIENTS AND METHODS: A 37-year-old African woman presented to the
      emergency department with severe headache, ocular pain, and no light perception
      in the left eye. The left pupil was middilated and nonreactive, and the
      intraocular pressure (IOP) by applanation tonometry was 47 mm Hg. Slit-lamp
      examination revealed anterior subcapsular opacification (glaukomflecken),
      posterior synechiae, and total angle closure with iris bombe. A fundus
      examination revealed macular exudation, inferior vascular dilation, and
      tortuosity with peripheral telangiectasia and macroaneurysms, in addition to
      partial exudative retinal detachment involving the macula. On the basis of these
      findings, Coats' disease was diagnosed. RESULTS: The patient was treated with
      antiglaucoma medications and laser peripheral iridotomy to control the IOP, which
      had decreased to 21 mm Hg the following day. Diode laser transscleral
      cyclophotocoagulation was performed to further decrease the IOP. After completing
      a 360 degree laser, the IOP decreased to 8 mm Hg and then stabilized around 12 mm
      Hg. The vision remained no light perception; however, the patient felt major
      symptomatic relief. CONCLUSIONS: The present case describes acute angle-closure
      glaucoma as an initial presentation of Coats' disease in adults. Clinicians
      should be aware that this unique presentation in Coats' disease can occur even
      without retinal detachment.

PMID- 29176336
TI  - Managing hypertriglyceridemia: What can we learn from cardiovascular outcomes
      trials?
AB  - Cardiovascular (CV) risk remains in some patients who are treated with statins.
      Evidence supports a role for triglycerides (TGs) in CV disease. TG-lowering agent
      outcomes studies have been inconsistent, but eicosapentaenoic acid significantly
      reduced coronary events in hypercholesterolemic patients who were treated with
      statins. Ongoing outcomes studies will clarify the role of TG-lowering treatments
      in CV risk reduction.

PMID- 29176334
TI  - Preclinical Optimization of a CD20-specific Chimeric Antigen Receptor Vector and
      Culture Conditions.
AB  - Chimeric antigen receptor (CAR)-based adoptive T-cell therapy is a highly
      promising treatment for lymphoid malignancies, and CD20 is an ideal target
      antigen. We previously developed a lentiviral construct encoding a third
      generation CD20-targeted CAR but identified several features that required
      additional optimization before clinical translation. We describe here several
      improvements, including replacement of the immunogenic murine antigen-binding
      moiety with a fully human domain, streamlining the transgene insert to enhance
      lentiviral titers, modifications to the extracellular IgG spacer that abrogate
      nonspecific activation resulting from binding to Fc receptors, and evaluation of
      CD28, 4-1BB, or CD28 and 4-1BB costimulatory domains. We also found that
      restimulation of CAR T cells with an irradiated CD20 cell line boosted cell
      growth, increased the fraction of CAR-expressing cells, and preserved in vivo
      function despite leading to a reduced capacity for cytokine secretion in vitro.
      We also found that cryopreservation of CAR T cells did not affect immunophenotype
      or in vivo antitumor activity compared with fresh cells. These optimization steps
      resulted in significant improvement in antitumor activity in mouse models,
      resulting in eradication of established systemic lymphoma tumors in 75% of mice
      with a single infusion of CAR T cells, and prolonged in vivo persistence of
      modified cells. These results provide the basis for clinical testing of a
      lentiviral construct encoding a fully human CD20-targeted CAR with CD28 and 4-1BB
      costimulatory domains and truncated CD19 (tCD19) transduction marker.

PMID- 29176337
TI  - Ethical Resources.
AB  - There is no way to underestimate the importance of the countless ways that ethics
      impacts case managers and the patients we serve. In fact, solid ethical decisions
      are such an integral part of case management practice that the Commission for
      Case Manager Certification has increased its number of continuing education units
      required for recertification. Discussion and resources are outlined in the
      Editorial.

PMID- 29176338
TI  - Case Managers on the Front Lines of Ethical Dilemmas: Advocacy, Autonomy, and
      Preventing Case Manager Burnout.
AB  - PURPOSE: The purpose of this article is to examine how case managers are
      routinely confronted by ethical dilemmas within a fragmented health care system
      and given the reality of financial pressures that influence life-changing
      decisions. The Code of Professional Conduct for Case Managers (Code), published
      by the Commission for Case Manager Certification, acknowledges "case managers may
      often confront ethical dilemmas" (Code 1996, Rev. 2015). PRIMARY PRACTICE
      SETTINGS: The Code and expectations that professional case managers, particularly
      those who are board certified, will uphold ethical and legal practice apply to
      case managers in every practice setting across the full continuum of health care.
      IMPLEMENTATIONS FOR CASE MANAGEMENT PRACTICE: This discussion acknowledges the
      ethical dilemmas that case managers routinely confront, which empowers them to
      seek support, guidance, and resources to support ethical practice. In addition,
      the article seeks to raise awareness of the effects of burnout and moral distress
      on case managers and others with whom they work closely on interdisciplinary
      teams.

PMID- 29176339
TI  - Patient and Nurse Experiences in a Rural Chronic Disease Management Program: A
      Qualitative Evaluation.
AB  - PURPOSE: Rural status confounds chronic disease self-management. The purpose of
      this qualitative, descriptive study was to evaluate the nurse-led "Living Well"
      chronic disease management program reporting patient recruitment and retention
      issues since program initiation in 2013. The Chronic Care Model (CCM) was the
      guiding framework used to reinforce that interdisciplinary teams must have
      productive patient interactions for their program(s) to be sustainable. PRIMARY
      PRACTICE SETTING: A rural, Midwest county clinic's chronic disease management
      program. METHODOLOGY AND SAMPLE: Observations, interviews, and within- and across
      case coding were used. Patients' responses were analyzed to identify (1) reasons
      for recruitment and retention problems and (2) program elements that were viewed
      as successful or needing improvement. A convenience sample of 6 rural, English
      speaking adults (65 years or older, with no severe cognitive impairment) with at
      least one chronic condition was recruited and interviewed. RESULTS: Themes
      emerged related to nurse knowledge, availability, and value; peer support;
      overcoming barriers; adherence enhancement; and family/friends' involvement.
      Patients reported engagement in self-management activities because of program
      elements such as support groups and productive nurse-patient interactions.
      Interdisciplinary communication, commitment, and patient referral processes were
      identified as reasons for recruitment and retention issues. IMPLICATIONS FOR CASE
      MANAGEMENT PRACTICE: Findings substantiated that certain elements must be present
      and improved upon for future rural programs to be successful. Interdisciplinary
      communication may need to be improved to address recruitment and retention
      problems. It was clear from patient interviews that the nurse coordinators played
      a major role in patients' self-management adherence and overall satisfaction with
      the program. This is important to case management because results revealed the
      need for programs of this nature that incorporate the vital role of nurse
      coordinators and align with the CCM value of providing a supportive community
      health care resource for patients with chronic disease.

PMID- 29176340
TI  - Working With Transgender Individuals in Case Management Practice.
AB  - PURPOSE AND OBJECTIVES: To understand key concepts, effective communication
      strategies, and a broad range of health and human services for transgender
      persons in order to enhance the effectiveness of case management services.
      PRIMARY PRACTICE SETTINGS: Individuals who identify as transgender or gender
      variant. FINDINGS/CONCLUSIONS: Transgender persons have faced historic challenges
      in accessing health care services that are respectful, sensitive, and affirming.
      Case managers have the opportunity to serve as an advocate for these individuals
      by understanding effective communication strategies as well as medical,
      behavioral, and social services to support transgender persons through the
      transition process. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: To be effective
      with transgender persons, case managers need to know key terms and communications
      strategies, medical treatment options, behavioral health issues that need to be
      evaluated and addressed, and social services available to transgender persons.

PMID- 29176341
TI  - Community-Based Home Health Programs and Chronic Disease: Synthesis of the
      Literature.
AB  - PURPOSE OF STUDY: This article reviewed and evaluated literature on the various
      community-based home health programs and their effectiveness at preventing
      hospital admissions in adults. The research question addressed is as follows: Do
      community-based home health programs decrease hospital admissions in adult
      patients with chronic disease? PRIMARY PRACTICE SETTING: The primary practice
      setting evaluated in this review of the literature was community-based home
      health programs. METHODOLOGY AND SAMPLE: In this literature review, a seven-step
      review method was utilized to assess the evidence. Three electronic databases
      were used to conduct the initial search inquiry: CINAHL (Cumulative Index to
      Nursing and Allied Health Literature) Plus with Full Text, Medline, and PsycINFO.
      The search parameters include research from 2006 through 2016, English-language
      studies, and research published in peer-reviewed journals. The following search
      terms were used in multiple combinations: community-based health programs,
      chronic disease, and home. The primary sample population assessed was older
      adults with chronic disease. RESULTS: The research identified three common themes
      that influenced quality-of-life outcomes and health care utilization in
      participants of a community-based home health program. These themes were
      encouragement and emotional support, home visits, and multidisciplinary
      coordination of care. Additional concepts of depression and educational
      reinforcement were also noted. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: This
      literature review indicates that community-based home health programs are a
      viable solution to providing cost-effective health care to the adult population
      with chronic diseases. Community-based home health programs have been shown to
      have a positive impact on the quality of life and a decrease in health care
      utilization, including emergency department and primary care practitioner visits
      and hospital admissions, for adults with chronic disease.

PMID- 29176342
TI  - The Things That No One Told Me.

PMID- 29176343
TI  - Important Message (IM) From Medicare: Simple Duty or Case Management Opportunity.

PMID- 29176344
TI  - Respecting Ethical Boundaries to Promote Patient-Centered Care.

PMID- 29176345
TI  - A Diabetes Case Management Study in a Rural Setting in India.

PMID- 29176348
TI  - Zika virus as a sexually transmitted pathogen.
AB  - PURPOSE OF REVIEW: Zika virus has recently emerged from an obscure mosquito-borne
      pathogen to an international public health concern. It is the first viral agent
      newly demonstrated to cause birth defects in several decades, and it is the only
      arbovirus now known to be transmitted sexually. The purpose of this review is to
      provide an overview of current understanding of sexual transmission of Zika virus
      and its possible clinical and public health consequences. RECENT FINDINGS: Sexual
      transmission of Zika virus has been reported from at least 13 countries without
      simultaneous mosquito-borne transmission; it is undoubtedly also occurring in
      countries with active arthropod transmission. Most published cases involve
      transmission from symptomatically infected men to women partners. Nevertheless,
      transmission from a symptomatic man to another man, from a symptomatic woman to a
      man, and from an asymptomatic man to a woman has also been reported. Sexual
      transmission has occurred before symptom onset, during illness, and after
      resolution of the source partner's symptoms. With the exception of a woman who
      developed symptomatic infection 44 days after onset of her husband's illness,
      nearly all instances reported to date have occurred within 20 days of the source
      partner's illness. Zika virus RNA has been detected in semen, saliva, blood,
      urine, and vaginal and cervical secretions; the length of time during which RNA
      can be detected varies widely across different body fluids but is especially
      lengthy in semen. Although semen has been found to contain ZIKV RNA for more than
      180 days after illness onset, only a small proportion of samples with detectable
      RNA yield replicative virus whenever cultured. SUMMARY: Public health agencies
      have promulgated interim recommendations to prevent sexual transmission of Zika
      virus; however, much remains unknown regarding the duration of contagiousness and
      risk factors for transmission. Given the risk for birth defects, the greatest
      concern is for transmission of the virus to women who are pregnant or attempting
      to become pregnant. To prevent sexual transmission in general, couples are
      advised to use condoms or not have sex for at least 6 months from the start of
      the male partner's symptoms or the date he was diagnosed with Zika or after he
      has returned from an area with risk of ZIKV infection. Women who have symptomatic
      ZIKV infection or have traveled to an area of risk are advised to use condoms or
      avoid sex for 8 weeks from the start of the woman's symptoms or the date she was
      diagnosed with Zika or after the woman returns from the area of risk.

PMID- 29176349
TI  - Epidemiology of community-acquired bacterial meningitis.
AB  - PURPOSE OF REVIEW: The epidemiology of bacterial meningitis has been dynamic in
      the past 30 years following introduction of conjugated vaccines against
      Haemophilus influenzae type B, Streptococcus pneumoniae and Neisseria
      meningitidis. The purpose of this review is to describe recent developments in
      bacterial meningitis epidemiology. RECENT FINDINGS: The incidence of bacterial
      meningitis in Western countries (Finland, Netherlands, and the United States)
      gradually declined by 3-4% per year to 0.7-0.9 per 100 000 per year in the past
      10-20 years. In African countries (Burkina Faso and Malawi), incidence rates are
      still substantially higher at 10-40 per 100 000 persons per year. Introduction of
      pneumococcal conjugate vaccines have not consistently decreased overall
      pneumococcal meningitis incidence because of serotype replacement. Following the
      introduction of serogroup A and C meningococcal vaccines, the incidence of
      meningococcal meningitis because of these serogroups strongly decreased. Novel
      outbreaks in the African meningitis belt by serogroup C and increased incidence
      of serogroup W in the United Kingdom and the Netherlands were observed recently.
      SUMMARY: Bacterial meningitis remains an important infectious disease, despite a
      gradual decline in incidence after large-scale vaccination campaigns. Further
      development of vaccines with broader coverage is important, as is continuous
      surveillance of bacterial meningitis cases.

PMID- 29176350
TI  - Low participation in organized colorectal cancer screening in France: underlying
      ethical issues.
AB  - International studies have shown a significant reduction in colorectal cancer
      (CRC) mortality following the implementation of organized screening programs,
      given a sufficient participation rate and adequate follow-up. The French national
      CRC screening program has been generalized since 2008 and targets 18 million men
      and women aged 50-74 years. Despite broad recommendations, the participation rate
      remains low (29.8%), questioning the efficiency of the program. A panel of
      experts was appointed by the French National Cancer Institute to critically
      examine the place of autonomy and efficiency in CRC screening and propose
      recommendations. In this paper, we explore the ethical significance of a public
      health intervention that falls short of its objectives owing to low take-up by
      the population targeted. First, we analyze the reasons for the low CRC screening
      participation. Second, we examine the models that can be proposed for public
      health actions, reconciling respect for the individual and the collective good.
      Our expert panel explored possible ways to enhance take-up of CRC screening
      within the bounds of individual autonomy, adapting awareness campaigns, and new
      educational approaches that take into account knowledge and analysis of
      sociocultural hurdles. Although public health actions must be universal, target
      actions should nonetheless be developed for nonparticipating population
      subgroups.

PMID- 29176351
TI  - Bacteremia in Patients With Liver Cirrhosis: Prevalence and Predictors of
      Multidrug Resistant Organisms.
AB  - GOALS: The objective of this study was to assess the prevalence and predictors of
      multidrug resistant organisms (MDRO) in cirrhotic patients with bacteremia at a
      large tertiary center in the United States. BACKGROUND: The epidemiology of
      bacteremia in patients with liver cirrhosis has not been well studied in the
      United States. STUDY: This case-case control study included 180 adults with liver
      cirrhosis hospitalized from 2011 to 2015. Case group 1 were patients with
      bacteremia due to a MDRO (n=30). Case group 2 were patients with bacteremia due
      to a non-MDRO (n=60). Control group comprised patients without bacteremia (n=90).
      MDRO was defined as bacteria that was nonsusceptible to >=1 agent in >=3
      antimicrobial categories. RESULTS: Of the 90 bacteremia episodes, 44% were
      because of gram-positive bacteria, 50% were because of gram-negative bacteria,
      and 6% were polymicrobial. MDROs caused 30 of 90 (33%) bacteremia episodes,
      including methicillin-resistant Staphylococcus species [12% (11/90)],
      fluoroquinolone-resistant Enterobacteriaceae [10% (9/90)], and Enterococcus
      faecium [3% (3/90)]. Eight percent of Enterobacteriaceae produced extended
      spectrum beta-lactamases. Four independent predictors of MDROs were identified:
      nonwhite race [adjusted odds ratio (aOR), 3.35; 95% confidence interval (CI),
      1.19-9.38], biliary cirrhosis (aOR, 11.75; 95% CI, 2.08-66.32), blood cultures
      obtained >48 hours after hospital admission (aOR, 6.02; 95% CI, 1.70-21.40), and
      recent health care exposure (aOR, 9.81; 95% CI, 2.15-44.88). CONCLUSIONS: A
      significant proportion of bacteremia in cirrhotic patients was due to MDROs at a
      large US tertiary care center. Local epidemiology data and identification of risk
      factors associated with MDROs may help with optimal empiric antibiotic selection.

PMID- 29176352
TI  - New science and treatment paradigms for atopic dermatitis.
AB  - PURPOSE OF THE REVIEW: The prevalence of atopic dermatitis is increasing in
      industrialized countries for unclear reasons. One theory centers on reduced
      exposure to microbes during infancy and childhood. Alterations in the epidermal
      permeability barrier, place certain patients at risk for the immunological
      dysfunction seen in atopic dermatitis. This review examines current research
      pertaining to the epidermal permeability barrier, the cutaneous microbiome, and
      the immunology of atopic dermatitis. New collaborative research has led to
      evidence-based management guidelines. RECENT FINDINGS: Increased skin barrier
      permeability and dysfunction of innate and adaptive immunity cause atopic
      dermatitis. Genetic and environmental factors leading to decreased filaggrin
      underlie many cases of atopic dermatitis. Defective epidermal barrier function
      allows for an increased density of Staphylococcus aureus and a subsequent shift
      in adaptive immunity to a type 2 immune response. Multiple evaluation and
      management guidelines have been published based on current available evidence.
      These guidelines highlight state of the art management of seven main areas:
      inflammation, infection, irritation, itch, ichthyosis (dry skin), immunological
      influences, and impeding (comorbid) conditions. SUMMARY: Pediatricians are
      central to the successful diagnosis and management of atopic dermatitis.
      Increased basic and clinical research and well published clinical guidelines will
      lead to improved outcomes for the patients and families affected by this chronic
      relapsing disorder.

PMID- 29176353
TI  - New developments in immunotherapy for pediatric leukemia.
AB  - PURPOSE OF REVIEW: Immunotherapy for the treatment of cancer has advanced at a
      tremendous pace over the last decade. In this review, we provide an overview of
      recent progress in immunotherapy for the treatment of leukemia, focusing on
      antibody-drug conjugates (ADC), bi-specific T-cell engagers (BiTE), and chimeric
      antigen receptor (CAR) T cells. RECENT FINDINGS: Ongoing clinical trials of CAR T
      cells directed against CD19 have produced complete remission rates as high as
      93%, prompting global multicenter phase 2 trials and the first FDA approval of a
      CAR T-cell therapy. Insights into cytokine release syndrome, a toxicity of CAR T
      cell therapy, and the cause for relapse after CAR T-cell therapy are evolving.
      The bispecific antibody blinatumomab and the ADCs inotuzumab and gemtuzumab have
      also recently received FDA approval for ALL and AML, respectively, moving these
      agents into a more prominent role in the relapse setting. SUMMARY: The use of
      immunotherapy for leukemia has been successful in creating durable remissions for
      multiply relapsed and refractory patients who previously had little chance of
      cure. The ongoing clinical and preclinical work continues to advance our
      understanding of these immune-based therapies, and will shape the next generation
      of clinical trials.

PMID- 29176354
TI  - Pediatric avulsion fractures of pelvis: current concepts.
AB  - PURPOSE OF REVIEW: Provide the reader with an evidence-based update on the
      importance of accurate diagnosis of commonly missed avulsion fractures of pelvis
      apophyses, the necessary imaging studies, the feared complications and the recent
      treatment recommendations. RECENT FINDINGS: Accurate diagnosis of avulsion
      fractures of pelvis apophyses is high yield as misdiagnosis leads to improper
      treatment. They should be differentiated from muscle strain and apophysitis.
      These fractures are usually associated with good outcomes; however, missed
      diagnosis can lead to further displacement, nonunion, functional limitation,
      femoroacetabular impingement and infection. A/P and frog lateral pelvis
      radiograph show the fracture and its displacement in the majority of cases.
      Conservative treatment, consisting of a short period of rest and immobilization
      followed by passive stretching then progressive resisted activity before return
      to sports, is recommended in minimally displaced avulsions. Surgical treatment is
      favored in displaced fractures (>15 mm), as it is associated with quicker return
      to sports. SUMMARY: Treating physicians should keep a high index of suspicion in
      pediatric and adolescent patients presenting with typical clinical exam findings.
      Pelvic Anteroposterior and frog leg radiographs are often diagnostic. Missed
      diagnosis can aggravate the prognosis of a usually benign condition. Adequate
      medical or surgical treatment should then be administered.

PMID- 29176355
TI  - What is the chance that a patella dislocation will happen a second time: update
      on the natural history of a first time patella dislocation in the adolescent.
AB  - PURPOSE OF REVIEW: Patellar instability occurs mainly in young patients and shows
      a high incidence of concomitant cartilage injuries. Recently there has been a
      strong attempt to identify risk factors and enhance imaging techniques to detect
      patients with an increased risk for recurrent patella dislocation.We describe
      current findings on factors associated with recurrent patella dislocation in the
      adolescent. RECENT FINDINGS: Trochlear dysplasia, patellar height, patellar tilt,
      tibial tuberosity-trochlear groove distance, skeletal maturity, and history of
      contralateral patellar dislocation are well known significant risk factors for
      recurrence in adolescent patients. Predictive models to calculate risk of
      recurrence have been reported recently. The Patellar Instability Severity Score
      was the first to include demographic and anatomic factors, which is of major
      value when counseling patients and relatives. SUMMARY: Several classification
      systems to predict the rate of recurrence after primary patella dislocation have
      been presented over the last years. Anatomic risk factors such as skeletal
      immaturity, trochlear morphology, patellar height, patellar tilt, and elevated
      tibial tuberosity-trochlear groove distance have been investigated. However,
      there is still a lack of knowledge as to how single risk factors or their
      interaction with each other may contribute.

PMID- 29176356
TI  - Evolving paradigms for new agent development in pediatric oncology.
AB  - PURPOSE OF REVIEW: To discuss considerations of new paradigms for clinical drug
      development in pediatric oncology that incorporate our expanding knowledge and
      complexity of molecular alterations associated with cancer; advances in cancer
      immunology and cellular therapy; the increasing number of new anticancer drugs,
      therapeutic approaches, and potential combinations; and recent initiatives by
      regulatory agencies to improve access to safe and effective therapies. RECENT
      FINDINGS: Cancer in children and adolescents is a rare event with significant
      long-term impact on individuals and society. Using multimodality therapy,
      stratified by patient and disease characteristics, the cure rate for childhood
      cancer exceeds 80%. Cancer genomics has transformed anticancer drug development.
      Understanding the genetic basis of pediatric cancers and the use of genomics for
      risk stratification has changed the focus of drug development from cytotoxic
      drugs to targeted therapeutic approaches. Advances in cancer immunology, immune
      checkpoint blockade, and cellular therapy offer novel approaches to harness T
      cells to treat cancer. To improve the outcome for children and adolescents with
      cancer and accelerate drug development, understanding drug and target
      interactions in preclinical models of pediatric cancer should be coupled with
      efficient clinical trial designs that incorporate biomarker selection, assessment
      of toxicity and drug exposure, and improved measures of response. SUMMARY:
      Clinical trials for children and adolescents with cancer evaluate cytotoxic
      drugs, molecularly target drugs, immunotherapy as well as combination therapies.
      The framework for oncology clinical trials will continually adapt to improve
      efficiency of trials and evaluate new therapeutic approaches.

PMID- 29176357
TI  - Human-papillomavirus-related disease in pediatrics.
AB  - PURPOSE OF REVIEW: Human papillomaviruses (HPVs) account for a number of distinct
      disease entities in pediatrics, ranging from common warts to the stigmatizing
      condyloma acuminata to life-threatening respiratory papillomatosis. Although
      there is still a lack of consensus on treatment for each of these HPV-related
      diseases, scientific investigation continues to progress. Increasing prevention
      of HPV-related disease with further vaccination and development of new vaccines
      continues to be the best medical strategy. RECENT FINDINGS: Although high-quality
      evidence for treatment of HPV-related disease is still lacking, several new
      studies have been published in recent years that have refined opinions on
      therapy. Novel treatments continue to be developed, including new vaccines to
      further coverage for other strains. SUMMARY: HPV-related disease in pediatrics is
      associated with societal stigmatization and a high level of morbidity. Greater
      understanding of the distinct diseases and high-quality research is necessary to
      enhance treatment selection in the coming future.

PMID- 29176358
TI  - Recent advances in pediatric oncology.

PMID- 29176359
TI  - Comparison of the Effectiveness of a Virtual Simulator With a Plastic Arm Model
      in Teaching Intravenous Catheter Insertion Skills.
AB  - The objective of this study was to compare the effectiveness of a virtual
      intravenous simulator with a plastic arm model in teaching intravenous catheter
      insertion skills to nursing students. We used a randomized controlled quasi
      experimental trial design and recruited 65 students who were assigned to the
      experimental (n = 33) and control (n = 32) groups using the simple random
      sampling method. The experimental group received intravenous catheterization
      skills training on the virtual intravenous simulator, and the control group
      received the same training on a plastic model of a human arm. Data were collected
      using the personal information form, intravenous catheterization knowledge
      assessment form, Intravenous Catheterization Skill Test, Self-Confidence and
      Satisfaction Scale, and Fear Symptoms Scale. In the study, the mean scores in the
      control group were 20.44 for psychomotor skills, 15.62 for clinical psychomotor
      skills, 31.78 for self-confidence, and 21.77 for satisfaction. The mean scores in
      the experimental group were 45.18 for psychomotor skills, 16.28 for clinical
      psychomotor skills, 34.18 for self-confidence, and 43.89 for satisfaction. The
      results indicated that psychomotor skills and satisfaction scores were higher in
      the experimental group, while the clinical psychomotor skills and self-confidence
      scores were similar in both groups. More students in the control group reported
      experiencing symptoms such as cold and sweaty hands, significant restlessness,
      and tense muscles than those in the experimental group.

PMID- 29176361
TI  - Active targeted delivery of immune therapeutics to lymph nodes.
AB  - PURPOSE OF REVIEW: Organ transplantation is a life-saving procedure and the only
      option for patients with end-organ failure. Immune therapeutics have been key to
      the success of organ transplantation. However, immune therapeutics are still
      unable to eliminate graft rejection and their toxicity has been implicated in
      poorer long-term transplant outcomes. Targeted nanodelivery has the potential to
      enhance not only the therapeutic index but also the bioavailability of the immune
      therapeutics. One of the key sites of immune therapeutics delivery is lymph node
      where the priming of immune cells occur. The focus of this review is on
      nanomedicine research to develop the targeted delivery of immune therapeutics to
      lymph nodes for controlling immune activation. RECENT FINDINGS: As nanomedicine
      creates its niche in clinical care, it provides novel immunotherapy platforms for
      transplant recipients. Draining lymph nodes are the primary loci of immune
      activation and represent a formidable site for delivery of wide variety of immune
      therapeutics. There have been relentless efforts to improve the properties of
      nanomedicines, to have in-depth knowledge of antigen and drug loading, and,
      finally, to explore various routes of passive and active targeted delivery to
      lymph nodes. SUMMARY: The application of nanotechnology principles in the
      delivery of immune therapeutics to the lymph node has created enormous excitement
      as a paradigm shifting approach that enables targeted delivery of a gamut of
      molecules to achieve a desired immune response. Therefore, innovative strategies
      that improve their efficacy while reducing their toxicity are among the highest
      unmet needs in transplantation.

PMID- 29176360
TI  - Intergenerational Consequences: Women's Experiences of Discrimination in
      Pregnancy Predict Infant Social-Emotional Development at 6 Months and 1 Year.
AB  - OBJECTIVE: Racial/ethnic and socioeconomic disparities in infant development in
      the United States have lifelong consequences. Discrimination predicts poorer
      health and academic outcomes. This study explored for the first time
      intergenerational consequences of women's experiences of discrimination reported
      during pregnancy for their infants' social-emotional development in the first
      year of life. METHODS: Data come from a longitudinal study with predominantly
      Black and Latina, socioeconomically disadvantaged, urban young women (N = 704,
      Mage = 18.53) across pregnancy through 1 year postpartum. Women were recruited
      from community hospitals and health centers in a Northeastern US city. Linear
      regression analyses examined whether women's experiences of everyday
      discrimination reported during pregnancy predicted social-emotional development
      outcomes among their infants at 6 months and 1 year of age, controlling for
      potentially confounding medical and sociodemographic factors. Path analyses
      tested if pregnancy distress, anxiety, or depressive symptoms mediated
      significant associations. RESULTS: Everyday discrimination reported during
      pregnancy prospectively predicted greater inhibition/separation problems and
      greater negative emotionality, but did not predict attention skills or positive
      emotionality, at 6 months and 1 year. Depressive symptoms mediated the
      association of discrimination with negative emotionality at 6 months, and
      pregnancy distress, anxiety, and depressive symptoms mediated the association of
      discrimination with negative emotionality at 1 year. CONCLUSION: Findings support
      that there are intergenerational consequences of discrimination, extending past
      findings to infant social-emotional development outcomes in the first year of
      life. It may be important to address discrimination before and during pregnancy
      and enhance support to mothers and infants exposed to discrimination to promote
      health equity across the life span.

PMID- 29176362
TI  - Significance of biologics in renal transplantation: past, present, and future.
AB  - PURPOSE OF REVIEW: Finding the right immunosuppressive approach for the
      individual transplant patient is of utmost importance. In truth, a 'one size fits
      all' does not exist, and as patients differ, so should therapeutic suppression of
      the immune system be individualized. For over three decades, biologics have been
      a central component of transplant immunosuppression. Our growing knowledge of
      immunological processes combined with biotechnological advances is leading to
      promising new therapeutic concepts and possibilities including novel biologics.
      Use of biologics may be appropriate at various phases of kidney transplantation,
      from desensitization and induction to maintenance therapy and management of acute
      rejection. Their mechanisms of action include depleting or modulating immune
      cells, eliminating preformed antibodies, and inhibiting the complement system.
      Herein, we summarize the current approaches to applying 'established' biologics
      to prevent and treat allograft rejection in kidney transplantation. We also
      provide insights into new developments and possible future directions. RECENT
      FINDINGS: A number of candidate biologics were found to be efficacious in more
      recent preclinical and early phase clinical trials. Their properties are outlined
      and their potential for future utilization discussed. SUMMARY: The extraordinary
      capabilities of biologics are undisputed and our technological progress offers
      unprecedented opportunities to devise new agents and refine old ones. However,
      the rationale for their use in kidney allograft recipients must be rigorously
      examined in every case and, given the significant risk of early and late-onset
      adverse effects, the risk-to-benefit ratio carefully balanced. We also need to
      expand and use our knowledge of the underlying physiology of allograft rejection
      to adjust the characteristics of therapeutic biologics and thus harness their
      full potential for the benefit of our patients.

PMID- 29176365
TI  - Parieto-occipital alopecia in early infancy mandates cranial imaging.

PMID- 29176366
TI  - Identification of a novel homozygous TBC1D24 mutation in a Turkish family with
      DOORS syndrome.

PMID- 29176367
TI  - Rare NaV1.7 variants associated with painful diabetic peripheral neuropathy.
AB  - Diabetic peripheral neuropathy (DPN) is a common disabling complication of
      diabetes. Almost half of the patients with DPN develop neuropathic pain (NeuP)
      for which current analgesic treatments are inadequate. Understanding the role of
      genetic variability in the development of painful DPN is needed for improved
      understanding of pain pathogenesis for better patient stratification in clinical
      trials and to target therapy more appropriately. Here, we examined the
      relationship between variants in the voltage-gated sodium channel NaV1.7 and NeuP
      in a deeply phenotyped cohort of patients with DPN. Although no rare variants
      were found in 78 participants with painless DPN, we identified 12 rare NaV1.7
      variants in 10 (out of 111) study participants with painful DPN. Five of these
      variants had previously been described in the context of other NeuP disorders and
      7 have not previously been linked to NeuP. Those patients with rare variants
      reported more severe pain and greater sensitivity to pressure stimuli on
      quantitative sensory testing. Electrophysiological characterization of 2 of the
      novel variants (M1852T and T1596I) demonstrated that gain of function changes as
      a consequence of markedly impaired channel fast inactivation. Using a structural
      model of NaV1.7, we were also able to provide further insight into the structural
      mechanisms underlying fast inactivation and the role of the C-terminal domain in
      this process. Our observations suggest that rare NaV1.7 variants contribute to
      the development NeuP in patients with DPN. Their identification should aid
      understanding of sensory phenotype, patient stratification, and help target
      treatments effectively.

PMID- 29176368
TI  - Changes in Case-Mix and Health Outcomes of Medicare Fee-for-Service Beneficiaries
      and Managed Care Enrollees During the Years 1992-2011.
AB  - BACKGROUND: Recent studies suggest that managed care enrollees (MCEs) and fee-for
      service beneficiaries (FFSBs) have become similar in case-mix over time; but
      comparisons of health outcomes have yielded mixed results. OBJECTIVE: To examine
      changes in differentials between MCEs and FFSBs both in case-mix and health
      outcomes over time. DESIGN: Temporal study of the linked Health and Retirement
      Study (HRS) and Medicare data, comparing case-mix and health outcomes between
      MCEs and FFSBs across 3 time periods: 1992-1998, 1999-2004, and 2005-2011. We
      used multivariable analysis, stratified by, and pooled across the study periods.
      The unit of analysis was the person-wave (n=167,204). SUBJECTS: HRS participants
      who were also enrolled in Medicare. MEASURES: Outcome measures included self
      reported fair/poor health, 2-year self-rated worse health, and 2-year mortality.
      Our main covariate was a composite measure of multimorbidity (MM), MM0-MM3,
      defined as the co-occurrence of chronic conditions, functional limitations,
      and/or geriatric syndromes. RESULTS: The case-mix differential between MCEs and
      FFSBs persisted over time. Results from multivariable models on the pooled data
      and incorporating interaction terms between managed care status and study period
      indicated that MCEs and FFSBs were as likely to die within 2 years from the HRS
      interview (P=0.073). This likelihood remained unchanged across the study periods.
      However, MCEs were more likely than FFSBs to report fair/poor health in the third
      study period (change in probability for the interaction term: 0.024, P=0.008),
      but less likely to rate their health worse in the last 2 years, albeit at
      borderline significance (change in probability: -0.021, P=0.059). CONCLUSIONS:
      Despite the persistence of selection bias, the differential in self-reported
      fair/poor status between MCEs and FFSBs seems to be closing over time.

PMID- 29176369
TI  - Payments and Utilization of Immunization Services Among Children Enrolled in Fee
      for-Service Medicaid.
AB  - OBJECTIVE: To examine the association between state Medicaid vaccine
      administration fees and children's receipt of immunization services. METHODS: The
      study used the 2008-2012 Medicaid Analytic eXtract data and included children
      aged 0-17 years and continuously enrolled in a Medicaid fee-for-service plan in
      each study year. Analyses were restricted to 8 states with a Medicaid managed
      care penetration rate <75%. Linear regressions were used to estimate the
      probability of children making >=1 vaccination visit and the numbers of
      vaccination visits in the year as a function of state Medicaid vaccine
      administration fees, age group, sex, race/ethnicity, state unemployment rate,
      state managed-care penetration rate, and state and year-fixed effects. RESULTS: A
      total of 1,678,288 children were included. In 2008-2012, the average proportion
      of children making >=1 vaccination visit per year was 31% and the mean number of
      vaccination visits was 0.9. State Medicaid reimbursements for vaccine
      administration was positively associated with immunization service utilization;
      for every $1 increase in the payment amount, the probability of children making
      >=1 vaccination visit increased by 0.72 percentage point (95% confidence
      interval, 0.23-1.21; P=0.01), representing a 2% increase from the mean and the
      number of vaccination visits increased by 0.03 (95% confidence interval, -0.00 to
      0.06; P<0.1). The estimated effect was greater among younger children.
      CONCLUSION: Higher Medicaid reimbursements for vaccine administration were
      associated with increased proportion of children receiving immunization services.

PMID- 29176370
TI  - Percutaneous Transhepatic Y-shaped Stent Placement in Portal-superior Mesenteric
      Vein Tumor Thrombosis Before Right Colectomy.
AB  - Portal-mesenteric tumor thrombosis represents a rare finding in patients with
      colorectal cancers. To our knowledge this is the first report of a patient
      diagnosed as having a wide stenosing right colon cancer with portal-superior
      mesenteric vein tumor thrombosis at the time of diagnosis, who was treated before
      surgery by positioning a percutaneous transhepatic Y-shaped stent through the
      main portal vein and the superior mesenteric vein. Percutaneous interventional
      procedures have gained worldwide acceptance for improving the symptoms of portal
      hypertension, because of their minimal invasiveness and high success rates with
      low number of complications. A multidisciplinary approach is mandatory in order
      to choose the best therapeutic option for the patients and the importance of a
      strong collaboration between interventional radiologist and surgeon has to be
      considered.

PMID- 29176371
TI  - Percutaneous Image-guided Surgery Training: Model IHU-DAICIM.
AB  - The evolution of guided imaging surgery is well known in recent years. As the
      field of action becomes more specific, learning and teaching are also more
      specific. State-of-the-art medical training should be mandatory in the field of
      general medicine and surgery in particular. In this work, we report on how to
      create a model for the formation of guided surgery by images in a simple and fast
      way, and its implementation by young surgeons. Pig models have been used in which
      collections made by bovine small intestine and simulated tumor lesions have been
      placed. Several types of image-guided procedures have been performed. No major
      complications were found during the development of the model or during its use.
      It is possible to develop a quick, simple, and safe living training model that
      can be used immediately after preparation.

PMID- 29176372
TI  - Application of Laparoscopic Gastrectomy in Obese Patients (BMI>=30 kg/m2) with
      Gastric Cancer: A Comparison With Open Gastrectomy Regarding Short-term Outcomes.
AB  - OBJECTIVE: Few studies have compared the surgical outcomes of laparoscopic (LG)
      and open (OG) gastrectomy in obese patients (BMI>=30 kg/m) with gastric cancer.
      The current study aimed to investigate the short-term outcomes of LG in this
      group of patients. METHODS: A total of 33 LG cases and 23 OG cases (BMI>=30 kg/m)
      were identified from our gastric cancer database. Clinicopathologic features,
      operative details, laboratory examination, and postoperative outcomes were
      compared between both groups. Regression analysis was used to determine the
      effects of BMI on intraoperative outcomes. RESULTS: The 2 groups had comparable
      clinicopathologic characteristics. LG was associated with significantly lesser
      blood loss, whereas both also groups had a similar operative time, and number of
      harvested lymph nodes. However, regression analysis indicated that increased BMI
      affected the operative time and blood loss in patients that underwent OG but had
      little effect on patients who received LG. The elevation of inflammatory factors
      (WBC, CRP) was lower in LG than in OG, postoperatively. Postoperative hepatic
      (alanine aminotransferase, total bilirubin, albumin) and renal (creatinine, blood
      urea nitrogen) functions in the LG group were not worse than in the OG group. The
      time to first flatus, initiation of diet, hospitalization, and postoperative
      complications seemed superior in LG than in OG, but these differences were not
      statistically significant. CONCLUSION: LG can be safely performed in obese
      gastric cancer patients. Compared with conventional OG, LG is less invasive and
      is characterized by less blood loss and milder surgical trauma. LG is also less
      adversely affected by increased BMI.

PMID- 29176373
TI  - Obstructive sleep apnea and bariatric surgical guidelines: summary and update.
AB  - PURPOSE OF REVIEW: Increasing numbers of bariatric surgical procedures and the
      high prevalence of obstructive sleep apnea (OSA) in this population have resulted
      in a growing interest in the perioperative management of OSA in bariatric
      surgery. This review provides a summary of the first consensus guideline on this
      topic as well as an update of the newest literature available. RECENT FINDINGS:
      All bariatric patients should be screened for OSA and obesity hypoventilation
      syndrome (OHS) to reduce the risk of perioperative complications. Intraoperative
      precautions are preoxygenation, induction and intubation in ramped position,
      continuous positive airway pressure (CPAP) and positive end-expiratory pressure
      during induction, maintenance of low tidal volumes during surgery, multimodal
      anesthesia and analgesia with avoidance of opioids and extubation when patients
      are free of neuromuscular blockage. CPAP therapy and continuous monitoring with a
      minimum of pulse oximetry is recommended in the early postoperative period.
      SUMMARY: Multiple precautions exist to minimize the risk of cardiopulmonary
      complications and to enhance recovery after surgery. A combination of these
      procedures seems to provide optimal perioperative care of OSA patients undergoing
      bariatric surgery. Nearly 75% of recommendations are based on low quality of
      evidence, indicating the high value of experts' opinion and potential for future
      research.

PMID- 29176374
TI  - Intraoperative vasoplegia: methylene blue to the rescue!
AB  - PURPOSE OF REVIEW: To evaluate the efficacy, dosing, and safety of methylene blue
      (MTB) in perioperative vasoplegic syndrome (VS). RECENT FINDINGS: Vasoplegic
      syndrome is a state of persistent hypotension with elevated cardiac output, low
      filling pressures, and low systemic vascular resistance (SVR). It occurs in up to
      25% of patients undergoing cardiac surgery with cardiopulmonary bypass, can last
      up to 72 h, and is associated with a high mortality rate. MTB has been found to
      increase SVR and decrease vasopressor requirements in vasoplegic syndrome by
      inhibiting nitric oxide synthase, thus limiting the generation of nitric oxide,
      while inhibiting activation of soluble guanylyl cyclase and preventing
      vasodilation. MTB has been used in postgraft reperfusion during liver
      transplantation and anaphylaxis in a limited number of cases. Additionally, this
      medication has been used in septic shock with promising results, but similar to
      the cardiac surgical population, the effects of MTB administration on clinical
      outcomes has yet to be elucidated. SUMMARY: MTB should be considered during
      vasoplegic syndrome in cardiac surgery with cardiopulmonary bypass and usage may
      be more effective in an early critical window, prior to end-organ hypoperfusion.
      Other perioperative scenarios of MTB use show promise, but additional studies are
      required to develop formative conclusions.

PMID- 29176376
TI  - Anticipated and unanticipated difficult airway management.
AB  - PURPOSE OF REVIEW: Management of difficult airway is far from optimal despite of
      continuous progress in science and technology. The purpose of this review is to
      summarize the current research in the field and bring readers up to date. RECENT
      FINDINGS: New technologies for intubation make providers more confident to handle
      difficult airways, but there is lack of evidence indicating the reduction in
      incidence of 'cannot intubate cannot ventilate (CICV)'. Optimization of mask
      ventilation should reduce the incidence of difficult mask ventilation but it is
      greatly underappreciated. Even optimization of preoxygenation is not directly
      associated with any decreased incidence of difficult airway, but it prolongs time
      of safe apnea oxygenation; therefore, is likely to improve the outcome of the
      patients if CICV occurs. SUMMARY: Improvement of managing difficult airway relies
      on optimized mask ventilation, utilization of the appropriate tools for
      intubation, maximization of the safe apnea oxygenation time, prompt surgical
      airway in response to severe hypoxia in case effective noninvasive interventions
      are not achievable. It seems that a simplified and concise algorithm of difficult
      airway management needs to be established in order to enable providers to easily
      remember and execute.

PMID- 29176375
TI  - Vitamin C in sepsis.
AB  - PURPOSE OF REVIEW: This narrative review summarizes recent insights into the role
      of vitamin C in sepsis. RECENT FINDINGS: Septic shock remains a major source of
      morbidity and mortality in critically ill patients. Although many nutritional
      supplements have previously been tested unsuccessfully, vitamins are still being
      explored as a therapeutic option in septic patients. In particular, vitamin C
      containing regimens as adjunctive therapy in sepsis have received much attention.
      SUMMARY: In-vitro evidence supports a critical role for vitamin C in cellular
      mechanisms relevant to the pathophysiology of sepsis. However, whether this
      justifies therapeutic use of vitamin C in septic patients remains uncertain.

PMID- 29176377
TI  - Pulmonary effects of aging.
AB  - PURPOSE OF REVIEW: As the population ages, the increase in chronic illnesses
      among patients with decreasing lung function will pose a major public health
      challenge. Determining which elderly patients are fit for surgery is an
      increasingly important skill. Anesthetic care of elderly patients requires an
      understanding of the effects that chronic diseases have on normal age-related
      changes in physiology and function. Postoperative respiratory complications are
      significantly increased in patients over 65 years of age, especially those with
      preexisting diseases. RECENT FINDINGS: Advanced age is associated with changes in
      the immunity of the pulmonary system. Dysregulation of pro-inflammatory mediators
      and antimicrobial defense systems contribute to a reduction in pulmonary function
      and its response to infections. Aging is also associated with a disruption of the
      function of alveolar macrophages, neutrophils, and natural killer cells. SUMMARY:
      Aging can increase the risk of postoperative complications because of a loss of
      physiologic reserve and airway defenses. These limitations may only become
      apparent after the stressors of surgery and anesthesia.

PMID- 29176378
TI  - Clinical characteristics and outcomes of patients with coronary artery spasm who
      initially presented with acute myocardial infarction.
AB  - BACKGROUND: The long-term clinical outcomes of coronary artery spasm (CAS)
      patients presented with acute myocardial infarction (AMI) compared to those who
      did not present with AMI has rarely been investigated. METHODS: From November
      2004 to May 2014, a total of 3360 patients who were confirmed as CAS by the
      acetylcholine (Ach) provocation test and without significant coronary lesion were
      retrospectively analyzed. AMI was an initial presentation in 34 patients [CAS
      myocardial infarction (MI) group], and not in other 3326 patients (CAS group).
      The clinical outcomes up to 5 years were compared between the two groups.
      RESULTS: Baseline characteristics and cardiovascular risk factors did not differ
      between the two groups, except the higher smoking rate in CAS-MI group (38.2 vs.
      23.5%, P=0.046). During a mean follow-up period of 1211+/-583 days, the
      cumulative incidence of recurrent angina [hazard ratio (HR): 2.71; 95% confidence
      interval (CI): 1.20-6.13; P=0.016], MI (HR: 33.89; 95% CI: 8.76-131.1; P<0.001)
      and major adverse cardiovascular events (MACE; HR: 10.94; 95% CI: 3.83-31.22;
      P<0.001) were significantly higher in the CAS-MI group. After propensity score
      matched analysis (1 : 5 matching; n=186, C-statistic=0.834), the incidences of
      recurrent angina (HR; 4.68; 95% CI: 1.62-13.5; P=0.004) and MACE (HR: 12.2; 95%
      CI: 2.23-67.3; P=0.003) remained higher in the CAS-MI group. CONCLUSION: The CAS
      MI group patients were associated with higher incidence of recurrent angina, MI,
      and MACE compared to CAS group patients. More intensive antispastic medication
      might be needed for these patients, and further study will be necessary to
      determine which treatment can improve the prognosis of CAS-MI patients.

PMID- 29176379
TI  - Thrombin generation estimates the anticoagulation effect of direct oral
      anticoagulants with significant interindividual variability observed.
AB  - : Direct oral anticoagulants (DOACs) are increasingly being used, primarily due
      to their drug stability and patient convenience. Although these drugs have been
      evaluated to be well tolerated in numerous clinical trials, their impact on in
      vivo anticoagulation effect, variability and therapeutic drug level remains
      unknown. Hence, we aim to study the effect and variability of DOACs on thrombin
      generation via the calibrated automated thrombogram. Anonymized coagulation
      specimens from outpatients on warfarin were collected. Pooled normal plasma
      samples were spiked with increasing concentrations of dabigatran, rivaroxaban and
      apixaban. Similarly, plasma samples with normal coagulation profiles were spiked
      with two concentrations each of dabigatran, rivaroxaban and apixaban. Thrombin
      generation via calibrated automated thrombogram was run using the above samples
      and compared with a dataset of normal controls. Increasing international
      normalized ratio was associated with a reduction of endogenous thrombin potential
      (ETP) and thrombin peak and increasing lag time. Factor Xa inhibitors produced a
      flattened thrombin generation curve with a reduction of thrombin peak and
      relative preservation of ETP. Direct thrombin inhibitors produced a reduction of
      both ETP and thrombin peak and increasing lag time. Seventy-one citrated plasma
      samples (26 dabigatran, 21 rivaroxaban and 24 apixaban) were evaluated. The two
      concentrations produced a reduction of thrombin generation parameters with
      significant interindividual variability compared with neat plasma of 35-93, 13-31
      and 18-71% and for dabigatran, rivaroxaban and apixaban, respectively. Thrombin
      generation can measure the anticoagulation effect of commonly used DOACs, with
      each drug having a unique thrombin generation profile. The variability noted
      using the same concentration suggests significant interindividual pharmacodynamic
      differences, which maybe relevant with respect to efficacy as well as bleeding
      side effects. Further delineation of the modifiers of interindividual differences
      is required in the in-vivo setting.

PMID- 29176380
TI  - Congenital hypofibrinogenemia in pregnancy: a report of 11 cases.
AB  - : To investigate the obstetrical outcomes and plasma concentrations of fibrinogen
      (FIB) in patients with congenital hypofibrinogenemia in pregnancy, 11 cases with
      hypofibrinogenemia in pregnancy were analyzed retrospectively. The demographic
      database, bleeding tendency, plasma levels of FIB throughout pregnancy,
      peripartum management, as well as, maternal and neonatal outcomes were assessed.
      FIB levels in our patients remained relatively stable throughout the pregnancy.
      The mean FIB levels during the three trimesters of pregnancy were 75.7 +/- 43.9
      (25-148), 67.6 +/- 33.7 (22-146), and 77.9 +/- 29.2 (32-148) mg/dl, respectively.
      Twelve full-term deliveries were achieved using FIB replacement therapy only on
      the group of labor or cesarean deliveries. The postpartum courses were
      unremarkable without hemorrhagic or thrombotic complications. Five out of twelve
      neonates were diagnosed with low levels of FIB in 6 weeks after birth. The
      pregnancies were uneventful with no signs of bleeding in these congenital
      hypofibrinogenemia women. Vaginal delivery, instead of cesarean section, may be
      the superior choice. Successful maternal and neonatal outcomes could be achieved
      by accurate monitoring of the FIB levels and adequate supportive therapy.

PMID- 29176381
TI  - Barriers to the Prescription of Psychological Strategies by Strength and
      Conditioning Specialists.
AB  - Radcliffe, JN, Comfort, P, and Fawcett, T. Barriers to the prescription of
      psychological strategies by strength and conditioning specialists. J Strength
      Cond Res 32(7): 1948-1959, 2018-The purpose of this article was to explore the
      barriers to strength and conditioning coaches integrating psychological
      strategies within the strength and conditioning practice. The sample of
      accredited strength and conditioning coaches comprised 10 subjects working within
      the United Kingdom, 3 within the United Sates, and 5 within Australia offering a
      cross section of experience from a range sporting disciplines and educational
      backgrounds. Subjects were interviewed using semistructured interviews and
      thematic clustering was used using interpretative phenomenological analysis to
      identify common themes. It was evident that not incorporating psychological
      strategies into strength and conditioning practice could be attributed to either
      internal, personally governed beliefs, or external, environmentally governed
      situations. Internal sources consisted of insufficient knowledge either regarding
      the value of psychological strategies or methods of implementing such techniques;
      in addition, the implementation of psychological techniques was outside the remit
      of the coach and difficulty existed in demonstrating the effectiveness of
      interventions. External causes consisted of a lack of time, insufficient control
      and authority of training session content, and athletes' negative perceptions.
      Recommendations are made on the basis of eliminating the observed barriers to the
      inclusion of psychological strategies. This included the use of education
      programs for both strength and conditioning coaches and organizational
      gatekeepers and the suggestion for increased collaboration with qualified
      psychologists.

PMID- 29176382
TI  - Independent and Combined Effects of Weight Status and Maturation on Aerobic
      Fitness in Adolescent School Aged Males.
AB  - This study aimed to examine the independent and combined effects of pubertal and
      weight status on concurrent measurements of peak oxygen (VO2peak) in school aged
      adolescent males. The final sample included 49 boys (12.3 +/- 0.8 years). VO2peak
      was derived from an incremental progressive maximal protocol using a motorized
      treadmill. In addition, maximal oxygen uptake was estimated from a 20-m shuttle
      run test. Static allometric models were obtained as an alternative to performance
      output per unit of size descriptors. Weight status had a significant effect on
      VO2peak using simple ratio standards per unit of body mass with adolescents
      classified as overweight and obese (OWOB) attaining lower values of VO2peak. A
      similar trend was noted for the allometric models adopting body mass (BM;
      mL.kgBM.min), stature (L.m.min) and fat-free mass (FFM; mL.kgFFM.min). Findings
      also suggest the influence and interaction of pubertal and weight status on
      absolute values of VO2peak. Considering the data obtained, linear equations to
      estimate VO2peak from the 20-m shuttle run test should not be applied to boys
      that are OWOB as it will produce inaccurate assessments of cardiorespiratory
      fitness and penalize those who are heavier. Equations for VO2peak prediction need
      to be specific for pubertal status and preferably consider FFM as a body size
      descriptor.

PMID- 29176383
TI  - Effect of Jump Interval Training on Kinematics of the Lower Limbs and Running
      Economy.
AB  - Ache-Dias, J, Pupo, JD, Dellagrana, RA, Teixeira, AS, Mochizuki, L, and Moro,
      ARP. Effect of jump interval training on kinematics of the lower limbs and
      running economy. J Strength Cond Res 32(2): 416-422, 2017-This study analyzed the
      effects of the addition of jump interval training (JIT) to continuous endurance
      training (40-minute running at 70% of peak aerobic velocity, 3 times per week for
      4 weeks) on kinematic variables and running economy (RE) during submaximal
      constant-load running. Eighteen recreational runners, randomized into control
      group (CG) or experimental group (EG) performed the endurance training. In
      addition, the EG performed the JIT twice per week, which consisted of 4-6 bouts
      of continuous vertical jumping (30 seconds) with 5-minute intervals. The oxygen
      consumption (V[Combining Dot Above]O2) during the submaximal test (performed at 9
      km.h) was similar before (EG: 38.48 +/- 2.75 ml.kg.min; CG: 36.45 +/- 2.70
      ml.kg.min) and after training (EG: 37.42 +/- 2.54 ml.kg.min; CG: 35.81 +/- 3.10
      ml.kg.min). No effect of training, group, or interaction (p > 0.05) was found for
      RE. There was no interaction or group effect for the kinematic variables (p >
      0.05). Most of the kinematic variables had a training effect for both groups
      (support time [p <= 0.05]; step rate [SR; p <= 0.05]; and step length [SL; p <=
      0.05]). In addition, according to the practical significance analysis (percentage
      chances of a better/trivial/worse effect), important effects in leg stiffness
      (73/25/2), vertical stiffness (73/25/2), SR (71/27/2), and SL (64/33/3) were
      found for the EG. No significant relationship between RE and stiffness were found
      for EG and CG. In conclusion, the results suggest that JIT induces important
      changes in the kinematics of the lower limbs of recreational runners, but the
      changes do not affect RE.

PMID- 29176384
TI  - Use of Mobile Applications to Collect Data in Sport, Health, and Exercise
      Science: A Narrative Review.
AB  - Peart, DJ, Balsalobre-Fernandez, C, and Shaw, MP. Use of mobile applications to
      collect data in sport, health, and exercise science: A narrative review. J
      Strength Cond Res XX(X): 000-000, 2018-Mobile devices are ubiquitous in the
      population, and most have the capacity to download applications (apps). Some apps
      have been developed to collect physiological, kinanthropometric, and performance
      data; however, the validity and reliability of such data is often unknown. An
      appraisal of such apps is warranted, as mobile apps may offer an alternative
      method of data collection for practitioners and athletes with money, time, and
      space constraints. This article identifies and critically reviews the
      commercially available apps that have been tested in the scientific literature,
      finding evidence to support the measurement of the resting heart through
      photoplethysmography, heart rate variability, range of motion, barbell velocity,
      vertical jump, mechanical variables during running, and distances covered during
      walking, jogging, and running. The specific apps with evidence, along with
      reported measurement errors are summarized in the review. Although mobile apps
      may have the potential to collect data in the field, athletes and practitioners
      should exercise caution when implementing them into practice as not all apps have
      support from the literature, and the performance of a number of apps have only
      been tested on 1 device.

PMID- 29176385
TI  - Positional Differences in Running and Nonrunning Activities During Elite American
      Football Training.
AB  - Ward, PA, Ramsden, S, Coutts, AJ, Hulton, AT, and Drust, B. Positional
      differences in running and nonrunning activities during elite American football
      training. J Strength Cond Res XX(X): 000-000, 2017-The aim of this investigation
      was to describe differences in training loads between position groups within
      professional American football. Integrated micro technology data were collected
      on 63 NFL football players during an American football training camp. Five key
      metrics (total distance, high-speed distance, player load (PL), PL per minute,
      and total inertial movement analysis [IMA]) served to quantify both running and
      nonrunning activities. Players were classified into position groups (defensive
      back [DB], defensive linemen [DL], linebacker, offensive linemen [OL],
      quarterback, running back, tight end, and wide receiver [WR]). Training sessions
      were identified by their relationship to the upcoming match (e.g., -4, -3, and 
      2). Running and nonrunning activities varied between position groups relative to
      the training day. Differences in total distance between DB and WR were observed
      to be unclear across the 3 training days (game day [GD] -4: 74 +/- 392 m; GD -3: 
      122 +/- 348 m; and GD -2: -222 +/- 371 m). However, moderate to large differences
      were observed between these 2 positions and the other positional groups. A
      similar relationship was observed in PL and PL per minute, with the DB and WR
      groups performing greater amounts of load compared with other positional groups.
      Differences in high-speed distance varied across positional groups, indicating
      different outputs based on ergonomic demands. The OL and DL groups ran less but
      engaged in a higher amount of nonrunning activities (total IMA) with differences
      ranging from moderate to large across the 3 training days. Total IMA differences
      between offensive and defensive linemen were unclear on GD -4 (-4 +/- 9) and GD 
      2 (-2 +/- 8) and likely moderate on GD -3 (-9 +/- 9). Positional differences with
      regard to running and nonrunning activities highlight the existence of position
      specific training within a training microcycle. In addition, total IMA provides a
      useful metric for quantifying sport-specific movements within the game of
      American football.

PMID- 29176386
TI  - Sex-Related Differences in The Accuracy of Estimating Target Force Using
      Percentages of Maximal Voluntary Isometric Contractions Versus Ratings of
      Perceived Exertion During Isometric Muscle Actions.
AB  - The purpose of this study was to examine sex-related differences in the accuracy
      of estimating actual target force and to compare the accuracy of estimating
      actual target force using percentages of maximal voluntary isometric contraction
      (MVIC) or ratings of perceived exertion (RPE) values during isometric leg flexion
      and leg extension muscle actions. Twenty adults, 10 women and 10 men, (mean +/-
      SD age: 22.9 +/- 2.9 yrs) completed pretest MVICs to calculate actual target
      force values at 10, 30, 50, 70, and 90% of MVIC. Additional trials were then
      randomized for estimating actual target force using percentages of MVIC or RPE
      values during isometric leg flexion or leg extension. For isometric leg flexion,
      the women and men overestimated (p<=0.05) the actual target force at 10% for the
      percentage of MVIC and RPE trial and underestimated the actual target force at
      90% for the RPE trial. For isometric leg extension, the women overestimated the
      actual target force at 10% for the percentage of MVIC trial and RPE trial. The
      men overestimated actual target force at 10% and 30% for the percentage of MVIC
      trial and overestimated actual target force at 10% during the RPE trial for
      isometric leg extension. Also, the men underestimated actual target force at 90%
      for both the percentage of MVIC trial and RPE trial. Men require more
      familiarization than women to accurately estimate isometric leg extension force
      values. Caution should be used when estimating force production as a percentage
      of MVIC or RPE value for training prescriptions.

PMID- 29176387
TI  - Effects of Plyometric and Directional Training on Speed and Jump Performance in
      Elite Youth Soccer Players.
AB  - Beato, M, Bianchi, M, Coratella, G, Merlini, M, and Drust, B. Effects of
      plyometric and directional training on speed and jump performance in elite youth
      soccer players. J Strength Cond Res 32(2): 289-296, 2018-Soccer players perform
      approximately 1,350 activities (every 4-6 seconds), such as
      accelerations/decelerations and changes of direction (CODs) during matches. It is
      well established that COD and plyometric training have a positive impact on
      fitness parameters in football players. This study analyzed the effect of a
      complex COD and plyometric protocol (CODJ-G) compared with an isolated COD
      protocol (COD-G) training on elite football players. A randomized pre-post
      parallel group trial was used in this study. Twenty-one youth players were
      enrolled in this study (mean +/- SD; age 17 +/- 0.8 years, mass 70.1 +/- 6.4 kg,
      and height 177.4 +/- 6.2 cm). Players were randomized into 2 different groups:
      CODJ-G (n = 11) and COD-G (n = 10), training frequency of 2 times a week more
      than 6 weeks. Sprint 10, 30, and 40 m, long jump, triple hop jump, and 505 COD
      test were considered. Exercise-induced within-group changes in performance for
      both CODJ-G and COD-G: long jump (effect size [ES] = 0.32 and ES = 0.26,
      respectively) and sprint 10 m (ES = -0.51 and ES = -0.22, respectively), after 6
      weeks of training. Moreover, CODJ-G reported substantially better results
      (between-group changes) in long jump test (ES = 0.32). In conclusion, this study
      showed that short-term protocols (CODJ-G and COD-G) are important and able to
      give meaningful improvements on power and speed parameters in a specific soccer
      population. CODJ-G showed a larger effect in sprint and jump parameters compared
      with COD-G after the training protocol. This study offers important implications
      for designing COD and jumps training in elite soccer.

PMID- 29176388
TI  - The Effect of Citrulline Malate Supplementation On Muscle Fatigue Among Healthy
      Participants.
AB  - The focus of the investigation was to examine the effects of citrulline malate on
      muscular fatigue in healthy, recreationally trained participants. Twelve
      participants (males = 6; females = 6) (24.1 +/- 3.9 yrs) visited the lab on three
      separate days all separated by one week. Each visit consisted of consuming one of
      three treatments: placebo (PLA), citrulline malate (8 g) (CM), and control (CON)
      in which no drink mixture was consumed. For each day of testing, participants
      consumed assigned treatment and performed one high-intensity exercise trial
      consisting of squats, lunge jumps, squat jumps, and lateral jumps. Participants
      performed the exercises in the listed order, which was designated as one round.
      Each participant performed 3 rounds, with the work to rest ratio being 20 sec
      work, 30 sec rest. A one min rest was given between rounds. A pre/post-exercise
      isokinetic leg extension test was performed to measure for peak power, peak
      torque, and rate of fatigue. Additionally, blood lactate was obtained pre/post
      exercise. There were no treatment or interaction effects (p > 0.05) for peak
      torque, peak power, rate of fatigue, or blood lactate accumulation. However,
      there was a statistical significant decrease from pre/post-ex for peak torque (p
      = 0.003), peak power (p = 0.003), and rate of fatigue (p = 0.001). Additionally,
      lactate accumulation did increase significantly from pre/post-ex (p = 0.0001).
      Lastly, neither total work nor final heart rate was statistical significant
      between the treatments (p > 0.05). Citrulline malate was not effective in
      improving performance or alleviating fatigue following a high-intensity exercise
      session.

PMID- 29176390
TI  - Methodological factors affecting quantification of blood pressure variability: a
      scoping review.
AB  - OBJECTIVES: Blood pressure (BP) variability (BPV) may offer independent
      prognostic information. However, data supporting this notion are inconsistent,
      and this may be due to the wide variety of methodologies used for measuring BPV.
      A systematic analysis on the effect of BPV methodologies on BPV itself has never
      been undertaken and was the aim of this study. We also sought to determine the
      effect of participant characteristics on BPV. METHODS: A scoping review process
      was used to identify the effect of BPV methodologies on BPV magnitude. Key
      methodological factors assessed were the number of BP readings or visits used to
      quantify BPV and the duration of BP monitoring. In addition, the relationship
      between age and mean BP level on BPV was investigated. Analyses were performed
      across studies that measured BPV over the short-term (using 24-h BP), mid-term
      (using home BP in the morning, evening or day-to-day) and long-term (using visit
      to-visit clinic BP). RESULTS: Data were extracted from 96 studies. The number of
      BP readings and visits used to quantify BPV were positively associated with mid
      term and long-term BPV. Duration was weakly associated with mid-term (morning)
      BPV. Age was positively associated with long-term and mid-term (day-to-day), but
      not short-term BPV. Mean BP level was positively associated with BPV, except mid
      term BPV (morning and evening). CONCLUSION: The methodology used to quantify BPV,
      as well as age and mean BP level, affects the magnitude of BPV itself. This
      highlights the need to standardize BPV protocols, particularly regarding the
      number of BP readings and visits.

PMID- 29176389
TI  - Contemporary genetic testing in inherited cardiac disease: tools, ethical issues,
      and clinical applications.
AB  - : Inherited cardiac diseases comprise a wide and heterogeneous spectrum of
      diseases of the heart, including the cardiomyopathies and the arrhythmic diseases
      in structurally normal hearts, that is, channelopathies. With a combined
      estimated prevalence of 3% in the general population, these conditions represent
      a relevant epidemiological entity worldwide, and are a major cause of cardiac
      morbidity and mortality in the young. The extraordinary progress achieved in
      molecular genetics over the last three decades has unveiled the complex molecular
      basis of many familial cardiac conditions, paving the way for routine use of gene
      testing in clinical practice. In current practice, genetic testing can be used in
      a clinically affected patient to confirm diagnosis, or to formulate a
      differential diagnosis among overlapping phenotypes or between hereditary and
      acquired (nongenetic) forms of disease. Although genotype-phenotype correlations
      are generally unpredictable, a precise molecular diagnosis can help predict
      prognosis in specific patient subsets and may guide management. In clinically
      unaffected relatives, genetic cascade testing is recommended, after the initial
      identification of a pathogenic variation, with the aim of identifying
      asymptomatic relatives who might be at risk of disease-related complications,
      including unexpected sudden cardiac death. Future implications include the
      identification of novel therapeutic targets and development of tailored
      treatments including gene therapy. This document reflects the multidisciplinary,
      'real-world' experience required when implementing genetic testing in
      cardiomyopathies and arrhythmic syndromes, along the recommendations of various
      guidelines.

PMID- 29176391
TI  - The relationship of all-cause mortality to average on-treatment systolic blood
      pressure is significantly related to baseline systolic blood pressure:
      implications for interpretation of the Systolic Blood Pressure Intervention Trial
      study.
AB  - BACKGROUND: The SPRINT study demonstrated that targeting systolic blood pressure
      (SBP) less than 120 mmHg was associated with lower cardiovascular event and
      mortality rates. In the LIFE study, however, a lower achieved SBP was associated
      with increased mortality. Mean baseline SBP in SPRINT was 140 mmHg and a third of
      the population had a baseline SBP 132 mmHg or less, raising the question of
      whether the lower baseline SBP in SPRINT could in part account for these
      differences. METHODS: All-cause mortality during 4.8 +/- 0.9 years follow-up was
      examined in relation to tertiles of achieved on-treatment average SBP in patients
      with baseline SBP of 25th percentile or less versus greater than 25th percentile
      value of 164 mmHg in 7998 nondiabetic hypertensive patients with ECG left
      ventricular hypertrophy randomly assigned to losartan-based or atenolol-based
      treatment. Average on-treatment SBP less than 142 mmHg (lowest tertile) and
      average SBP 142 mmHg to less than 152 mmHg (middle tertile) were compared with
      average SBP at least 152 mmHg (highest tertile and reference group). RESULTS: In
      the overall population, there was a significant interaction between baseline SBP
      164 mmHg or less and average on-treatment SBP less than 142 mmHg in Cox analysis
      (chi = 15.48, P < 0.001). Among patients with baseline SBP greater than 164 mmHg,
      in multivariate Cox analyses adjusting for other potential predictors of
      mortality and a propensity score for having baseline SBP 164 mmHg or less and
      compared with average on-treatment SBP at least 152 mmHg, average on-treatment
      SBP less than 142 mmHg was associated with 32% higher mortality (hazard ratio
      1.32, 95% CI 1.01-1.65), whereas average SBP of 142 mmHg to less than 152 mmHg
      was associated with 24% lower mortality (hazard ratio 0.76, 95% CI 0.59-0.98). In
      contrast, among patients with baseline SBP 164 mmHg or less, both average on
      treatment SBP less than 142 mmHg (hazard ratio 0.60, 95% CI 0.36-0.99) and
      average SBP of 142 mmHg to less than 152 mmHg (hazard ratio 0.51, 95% CI 0.30
      0.89) were associated with significantly lower mortality compared with average
      SBP of at least 152 mmHg. CONCLUSION: Achievement of an average SBP less than 142
      mmHg was associated with reduced mortality in patients with baseline SBP 164 mmHg
      or less but with increased mortality in those with higher baseline SBP in LIFE.
      These findings suggest that the lower mortality associated with a lower targeted
      SBP in SPRINT may not be applicable to patients with considerably higher baseline
      SBP than SPRINT patients. Further study is necessary to better understand these
      findings. CLINICAL TRIALS REGISTRATION:
      http://clinicaltrials.gov/ct/show/NCT00338260?order=1.

PMID- 29176392
TI  - Expanding the Use of Organs From Hepatitis C-Viremic Donors: The Evidence
      Continues to Build.

PMID- 29176393
TI  - Editorial: mood and anxiety disorders.

PMID- 29176394
TI  - Hearing Loss in Children With Otitis Media With Effusion: Actual and Simulated
      Effects on Speech Perception.
AB  - OBJECTIVE: Conductive hearing loss simulations have attempted to estimate the
      speech-understanding difficulties of children with otitis media with effusion
      (OME). However, the validity of this approach has not been evaluated. The
      research aim of the present study was to investigate whether a simple, frequency
      specific, attenuation-based simulation of OME-related hearing loss was able to
      reflect the actual effects of conductive hearing loss on speech perception.
      DESIGN: Forty-one school-age children with OME-related hearing loss were
      recruited. Each child with OME was matched with a same sex and age counterpart
      with normal hearing to make a participant pair. Pure-tone threshold differences
      at octave frequencies from 125 to 8000 Hz for every participant pair were used as
      the simulation attenuation levels for the normal-hearing children. Another group
      of 41 school-age otologically normal children were recruited as a control group
      without actual or simulated hearing loss. The Mandarin Hearing in Noise Test was
      utilized, and sentence recall accuracy at four signal to noise ratios (SNR)
      considered representative of classroom-listening conditions were derived, as well
      as reception thresholds for sentences (RTS) in quiet and in noise using adaptive
      protocols. RESULTS: The speech perception in quiet and in noise of children with
      simulated OME-related hearing loss was significantly poorer than that of
      otologically normal children. Analysis showed that RTS in quiet of children with
      OME-related hearing loss and of children with simulated OME-related hearing loss
      was significantly correlated and comparable. A repeated-measures analysis
      suggested that sentence recall accuracy obtained at 5-dB SNR, 0-dB SNR, and -5-dB
      SNR was similar between children with actual and simulated OME-related hearing
      loss. However, RTS in noise in children with OME was significantly better than
      that for children with simulated OME-related hearing loss. CONCLUSIONS: The
      present frequency-specific, attenuation-based simulation method reflected the
      effects of OME-related hearing loss on speech perception impairment in quiet
      environments. In noisy environments, the simulation method could only
      approximately estimate the effects of OME-related hearing loss on speech
      perception in typical classroom noise levels. Children with OME-related hearing
      loss may develop compensatory strategies to reduce the effects of hearing loss in
      adverse listening environments.

PMID- 29176395
TI  - Integrated safety summary for trifluridine/tipiracil (TAS-102).
AB  - Trifluridine/tipiracil, an oral treatment combining trifluridine (an
      antineoplastic thymidine-based nucleoside analog) and tipiracil hydrochloride (a
      thymidine phosphorylase inhibitor), led to significant improvement in overall
      survival in metastatic colorectal cancer (mCRC) patients refractory to standard
      therapy in the phase III RECOURSE trial. Here, we report an integrated summary of
      the safety of trifluridine/tipiracil. The main safety analysis includes
      integrated data from the RECOURSE and J003 studies (safety data group 2) of
      patients with refractory mCRC receiving trifluridine/tipiracil at the recommended
      starting dose: 35 mg/m twice daily for 5 days with 2 days' rest for 2 weeks,
      followed by a 14-day rest (one cycle). Integrated data from a larger group of
      mCRC patients receiving trifluridine/tipiracil at the recommended starting dose
      (group 1) and nonintegrated data on serious adverse events (SAEs) representing
      all clinical experience with trifluridine/tipiracil as of the data cutoff date
      (group 3) are also summarized. In group 2, myelosuppressive and all-grade
      gastrointestinal adverse events (AEs) were more frequent in
      trifluridine/tipiracil patients than in placebo patients. The
      trifluridine/tipiracil and placebo patients had similar frequencies of AEs
      leading to discontinuation (9.0 vs. 11.5%) and SAEs (27.7 vs. 29.2%); fatal AEs
      were more frequent in placebo patients than in trifluridine/tipiracil patients
      (9.3 vs. 2.8%). AEs leading to interruptions/delays/reductions were more frequent
      in trifluridine/tipiracil patients (56.3 vs. 12.7%). Trifluridine/tipiracil was
      generally well tolerated, but over 50% of patients required
      interruptions/delays/reductions. There was a low rate of discontinuations, SAEs,
      and fatal AEs. This analysis confirms the safety profile observed in RECOURSE.

PMID- 29176396
TI  - Histone deacetylase inhibitor SAHA-induced epithelial-mesenchymal transition by
      upregulating Slug in lung cancer cells.
AB  - SAHA, a member of histone deacetylase inhibitors (HDACIs), which emerged as a
      class of novel antitumor drug, has been used in clinical treatment of cancers.
      However, clinical experience of SAHA in solid tumors has been disappointing.
      Nevertheless, the underlying mechanism of this deficiency is not clearly
      understood. In the present study, we found that SAHA could induce epithelial
      mesenchymal transitions (EMT) in lung cancer A549 cells, which was associated
      with increased migration capability and cellular morphology changes. We showed
      that SAHA decreased epithelial marker E-cadherin's expression and increased the
      expression of mesenchymal marker vimentin. SAHA upregulated the protein and mRNA
      expression of transcription factor Slug in a time-dependent manner and promoted
      its nuclear translocation. We further demonstrated that SAHA upregulated Slug
      expression by promoting Slug acetylation but not influencing the phosphorylation
      of GSK-3beta, a main kinase-controlled Slug expression. Finally, silencing of
      Slug by siRNA reversed EMT marker expressions and cellular morphology change
      induced by SAHA, suggesting that Slug plays a crucial role in SAHA-mediated EMT
      in A549 cells. Our research study provided a better understanding of treatment
      failure of SAHA in patients with solid tumors. Therefore, more attention should
      be paid to cancer treatment using SAHA and strategies for reversing EMT before
      using SAHA would be better if the value of SAHA in the treatment of solid tumors,
      especially lung cancer, is realized.

PMID- 29176397
TI  - A case of heavily pretreated metastatic cardiac angiosarcoma treated successfully
      using eribulin.
AB  - Eribulin mesylate (eribulin) is a nontaxane microtubule inhibitor approved in
      Japan for treating soft tissue sarcoma irrespective of histological subtypes.
      Thus, our department routinely uses eribulin to treat any histological subtype of
      sarcoma for patients who have experienced disease progression during standard
      therapy. However, evidence on the efficacy of eribulin in treating sarcomas that
      are neither liposarcoma nor leiomyosarcoma is limited. Recently, we encountered a
      case of a heavily pretreated cardiac angiosarcoma that responded well to eribulin
      treatment. The patient was a 34-year-old Japanese woman with advanced
      angiosarcoma, who had been pretreated heavily using several lines of
      chemotherapy. Eribulin was administered as the eighth line of treatment and the
      dose was adjusted because of grade 4 neutropenia. After three cycles of
      treatment, contrast-enhanced computed tomography showed a partial tumor response,
      which was sustained for ~4 months. This case suggests that eribulin may be a
      potential therapeutic option for angiosarcoma. Further studies are needed to
      confirm the benefit of eribulin for patients with angiosarcoma and to establish
      predictive markers for eribulin sensitivity.

PMID- 29176398
TI  - The role of the globular heads of the C1q receptor in paclitaxel-induced human
      ovarian cancer cells apoptosis by a mitochondria-dependent pathway.
AB  - As a mitochondrial membrane protein, globular C1q receptor (gC1qR) can mediate a
      variety of biological responses. Our study aims to investigate the role of gC1qR
      in paclitaxel-induced apoptosis of human ovarian cancer cells and to elucidate
      its potential molecular mechanism. The level of gC1qR was examined using real
      time PCR and western blot analyses. Human ovarian cancer cells viability,
      migration, and proliferation were detected using the water-soluble tetrazolium
      salt (WST-1) assay, the transwell assay, and H-thymidine incorporation into DNA
      (H-TdR) assay, respectively. Apoptosis in cells was assessed using flow
      cytometric analysis. The intracellular reactive oxygen species was estimated by
      the fluorescence of H2DCFDA and the mitochondrial membrane potential was tested
      using a JC-1 probe. The expression of the gC1qR gene decreased significantly in
      human ovarian cancer tissues relative to the surrounding non-neoplastic ovarian
      tissues. Cells treated with paclitaxel showed increased gC1qR gene expression,
      cell apoptosis, and mitochondria dysfunction, and the effects on these cells
      could be abrogated by the addition of gC1qR small-interfering RNA or alpha-lipoic
      acid that was used to protect the mitochondria function. In summary, these data
      support a mechanism that gC1qR-induced mitochondria dysfunction was involved in
      the paclitaxel-mediated apoptosis of ovarian cancer cells.This is an open-access
      article distributed under the terms of the Creative Commons Attribution-Non
      Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to
      download and share the work provided it is properly cited. The work cannot be
      changed in any way or used commercially without permission from the journal.
      http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 29176399
TI  - New instrumentations in the operating room for sinus surgery.
AB  - PURPOSE OF REVIEW: The article reviews the advancements in instrumentation in the
      operating room that augment the speed, safety or outcomes of endoscopic sinus
      surgery (ESS). The article aims to update the Rhinologist on recent perioperative
      instruments that may benefit their practice. RECENT FINDINGS: The greatest
      advancements in the recent years have been in the field of visualization and
      optics. The introduction of high definition and ultra high definition 4K camera
      and screens supported by improvements with three-dimensional and variable angled
      endoscopes have greatly enhanced the quality and range of the visual information
      available to the sinus surgeon. This is closely supported by flexibility and
      enhanced functionality of the powered instrumentation with bipolar, monopolar and
      malleable blades and ever increasing more powerful burs. SUMMARY: Recent years
      have seen notable developments in the areas of optics, cameras and powered
      instruments to support the sinus surgeon. This article summarizes these
      developments and highlights the major benefits of these developments.

PMID- 29176400
TI  - Cost-effectiveness analysis of HLA-B*58: 01 genetic testing before initiation of
      allopurinol therapy to prevent allopurinol-induced Stevens-Johnson syndrome/toxic
      epidermal necrolysis in a Malaysian population.
AB  - OBJECTIVE: Studies found a strong association between allopurinol-induced Stevens
      Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the HLA-B*58:01
      allele. HLA-B*58:01 screening-guided therapy may mitigate the risk of allopurinol
      induced SJS/TEN. This study aimed to evaluate the cost-effectiveness of HLA
      B*58:01 screening before allopurinol therapy initiation compared with the current
      practice of no screening for Malaysian patients with chronic gout in whom a
      hypouricemic agent is indicated. METHODS: This cost-effectiveness analysis
      adopted a societal perspective with a lifetime horizon. A decision tree model
      coupled with Markov models were developed to estimate the costs and outcomes,
      represented by quality-adjusted life years (QALYs) gained, of three treatment
      strategies: (a) current practice (allopurinol initiation without HLA-B*58:01
      screening); (b) HLA-B*58:01 screening before allopurinol initiation; and (c)
      alternative treatment (probenecid) without HLA-B*58:01 screening. The model was
      populated with data from literature review, meta-analysis, and published
      government documents. Cost values were adjusted for the year 2016, with costs and
      health outcomes discounted at 3% per annum. A series of sensitivity analysis
      including probabilistic sensitivity analysis were carried out to determine the
      robustness of the findings. RESULTS: Both HLA-B*58:01 screening and probenecid
      prescribing were dominated by current practice. Compared with current practice,
      HLA-B*58:01 screening resulted in 0.252 QALYs loss per patient at an additional
      cost of USD 322, whereas probenecid prescribing resulted in 1.928 QALYs loss per
      patient at an additional cost of USD 2203. One SJS/TEN case would be avoided for
      every 556 patients screened. At the cost-effectiveness threshold of USD 8695 per
      QALY, the probability of current practice being the best choice is 99.9%, in
      contrast with 0.1 and 0% in HLA-B*58:01 screening and probenecid prescribing,
      respectively. This is because of the low incidence of allopurinol-induced SJS/TEN
      in Malaysia and the lower efficacy of probenecid compared with allopurinol in
      gout control. CONCLUSION: This analysis showed that HLA-B*58:01 genetic testing
      before allopurinol initiation is unlikely to be a cost-effective intervention in
      Malaysia.

PMID- 29176401
TI  - 2017 Military Supplement: Dodecafluoropentane Emulsion (Ddfpe) as a Resuscitation
      Fluid for Treatment of Hemorrhagic Shock and Traumatic Brain Injury: A Review.
AB  - Dodecafluoropentane emulsion (DDFPe) is a novel nanotechnology for oxygen
      delivery with therapeutic potential for hemorrhagic shock and/or traumatic brain
      injury (TBI). DDFPe demonstrates efficacy at smaller doses than previously tested
      perfluorocarbon oxygen therapeutics. This smaller dose potentially eliminates
      toxicities exhibited by previous oxygen therapeutics, while anti-inflammatory
      properties of DDFPe may alleviate damage from ischemia reperfusion injury. This
      mini-review summarizes our progress in developing a battle-field ready product to
      prevent combat death due to hemorrhagic shock and/or TBI. Preclinical studies,
      for both indications, show promising effects of DDFPe as a resuscitation fluid.
      DDFPe may become a part of the toolkit for tactical healthcare professionals in
      battlefield and domestic emergency medicine.

PMID- 29176402
TI  - Clinical Outcomes of Minimized Hydrocortisone Dosage of 100 Mg/Day on Lower
      Occurrence of Hyperglycemia in Septic Shock Patients.
AB  - BACKGROUND: The current international guideline recommended 200 mg/day of
      hydrocortisone intravenously to treat septic shock. However, a subsequent study
      on cortisol metabolism actually showed an increase in cortisol level during
      sepsis. Hence, the smaller hydrocortisone dose of 100 mg/day might be sufficient
      and reduce steroid-associated complications. We aimed to compare the clinical
      outcomes of minimized hydrocortisone dose of 100 mg to the currently recommended
      dose in the treatment of septic shock patients. METHODS: A double-blinded
      randomized controlled trial included 80 septic shock patients with hemodynamic
      instability despite fluid and vasopressive therapy. Participants were divided
      equally into two groups to treat with 100 mg/day or 200 mg/day of hydrocortisone,
      then stepwise down titrated and discontinued on day 8. The outcome of interest
      was the hyperglycemic rate. Vital status, time to shock reversal, superinfection
      and gastrointestinal bleeding rates were also compared. RESULTS: Patients with
      100 mg hydrocortisone had significantly lower hyperglycemic rate compared with
      200 mg, 63.9% versus 86.5% (the adjusted hazard ratio [HR], 0.08; 95% confidence
      interval [CI], 0.02-0.41, P = 0.002). Time to shock reversal was shorter in
      patients with 100 mg hydrocortisone, 2 days vs. 4 days, P = 0.031. The 28-day
      mortality rate when adjusted for Simplified Acute Physiology Score II showed no
      significant difference (HR, 0.68; 95% CI, 0.37-1.24, P = 0.209). The reinfection
      and gastrointestinal bleeding rates were comparable between groups. CONCLUSION:
      Minimized daily hydrocortisone dosage of 100 mg could lower the occurrence of
      hyperglycemia without increasing mortality in septic shock, compared with the
      currently recommended dosage of 200 mg/day.

PMID- 29176403
TI  - TLR4 and NLRP3 Caspase 1- IL-1beta- Axis are not Involved in Colon Ascendens
      Stent Peritonitis (Casp)-Associated Heart Disease.
AB  - Hemodynamic collapse and myocardial dysfunction are among the major causes of
      death in severe sepsis. The purpose of this study was to assess the role played
      by TLR4 and by the NLRP3 inflammasome in the cardiac dysfunction that occurs
      after high-grade polymicrobial sepsis. We performed the colon ascendens stent
      peritonitis (CASP) surgery in Tlr4, Nlrp3 and caspase-1 mice. We also assessed
      for the first time the electrical heart function in the CASP model. The QJ
      interval was increased in wild-type C57BL/6J mice after CASP when compared to
      sham controls, a result paralleled by an increase in the cardiac action potential
      duration (APD). The decreases in ejection fraction (EF), left-ventricle end
      diastolic volume (LVEDV), stroke volume, and cardiac output found after CASP were
      similar among all groups of mice. Similar heart response was found when Nlrp3
      mice were submitted to high-grade CLP. Despite developing cardiac dysfunction
      similar to wild-types after CASP, Nlrp3 mice had reduced circulating levels of IL
      1beta, IL-6 and TNF-alpha. Our results demonstrate that the genetic ablation of
      Tlr4, Nlrp3, and caspase-1 does not prevent the cardiac dysfunction, despite
      preventing the increase in pro-inflammatory cytokines, indicating that these are
      not feasible targets to therapy in high-grade sepsis.

PMID- 29176404
TI  - Antiplatelet Therapy for Critically Ill Patients: A Pairwise and Bayesian Network
      Meta-Analysis.
AB  - Antiplatelet therapy is an attractive treatment option for critically ill
      patients. However, more evidence on the benefit of this therapy is required. We
      searched the PubMed and Embase databases from their inception to June 2017 for
      randomized controlled trials and observational studies that assess the effect of
      antiplatelet therapy in critically ill patients. Antiplatelet therapy resulted in
      significant decreases in hospital mortality (risk ratio [RR] 0.81, 95% confidence
      interval [CI], 0.68-0.97; P = 0. 025), intensive care unit (ICU) mortality (RR
      0.78, 95% CI, 0.63-0.97; P = 0. 027), incidence of respiratory distress syndrome
      or acute lung injury (RR 0.73, 95% CI, 0.58-0.91; P = 0.006), and incidence of
      sepsis (RR 0.81, 95% CI, 0.68-0.97; P = 0.021). A predefined subgroup analysis
      according to patient type suggested that hospital mortality and ICU mortality
      benefits were seen only in septic patients (RR 0.71, 95% CI, 0.58-0.86; P <
      0.0001) and (RR 0.65, 95% CI, 0.49-0.86; P = 0.002). By network meta-analysis,
      the predictive interval plot showed that patients treated with aspirin and
      clopidogrel had lower risk of hospital mortality as compared with control group.
      The assessment of rank probabilities using SUCRA plots indicated that aspirin
      presented the greatest likelihood of having lowest hospital mortality rate. The
      results of this meta-analysis suggest that antiplatelet therapy is useful for the
      treatment in critically ill patients, and this is primarily due to an effect on
      septic patients. Network meta-analysis shows that the probability of being the
      best antiplatelet therapy for critically ill patients was aspirin.

PMID- 29176405
TI  - Lipopeptide PAM3CYS4 Synergizes N-Formyl-Met-Leu-Phe (fMLP)-Induced Calcium
      Transients in Mouse Neutrophils.
AB  - N-Formyl-Met-Leu-Phe (fMLP), a mimic of N-formyl oligopeptides that are released
      from bacteria, is a potent leukocyte chemotactic factor. It induces intracellular
      calcium ([Ca]i) transient that is important for various neutrophil biological
      functions, e.g., adhesion, ROS, and cytokine productions. Toll-like receptors
      (TLRs), an essential part of host innate immunity, regulate neutrophil
      activities, but their role in [Ca]i signaling is less clear. In the present
      study, we examined the effect of several TLR ligands, including Pam3Cys4
      (TLR1/2), lipopolysaccharide (LPS, TLR4), and lipoteichoic acid (LTA, TLR2/6), on
      calcium signaling and on the fMLP-induced [Ca]i transients in mouse neutrophils
      loaded with Fura-2/AM. We found that unlike fMLP, the three TLR ligands tested
      did not elicit any detectable Ca flux. However, Pam3Cys4, but not LPS or LTA,
      markedly synergized the fMLP-induced [Ca]i transients, and had no effect on the
      host component keratinocyte-derived cytokine (KC)- or C5a-induced calcium flux.
      The effect of Pam3Cys4 on the fMLP-induced [Ca]i transients is by enhancing
      extracellular Ca influx, not intracellular Ca release. Surprisingly, deletion of
      TLR2 or MyD88 in neutrophils had no impact on the Pam3Cys4's effect, suggesting a
      TLR2-MyD88-independent mechanism. Finally, using the pan PKC activator and
      inhibitor, we demonstrated that PKC negatively regulated fMLP-induced [Ca]i
      transients and that inhibition of PKC did not prohibit Pam3Cys4's synergistic
      effect on the fMLP-induced calcium influx. In conclusion, the present study
      identified a novel synergistic effect of Pam3Cys4 on fMLP-induced [Ca]i
      transients, a process important for many neutrophil biological functions.

PMID- 29176406
TI  - Walking Aids for Enabling Activity and Participation: A Systematic Review.
AB  - In this systematic literature review, we examined whether and how walking aids
      (i.e., canes, crutches, walkers, and rollators) enable activity and participation
      among adults with physical disabilities. Medline, Embase, all EBM reviews,
      PsychInfo, CINAHL, and Web of Science databases were used to identify studies
      published since 2008. Quantitative and qualitative designs were included. Data
      regarding participants, assistive device use, outcome measures, and domains of
      participation were extracted. Two reviewers independently rated the level of
      evidence and methodological quality of the studies. Outcomes were categorized per
      types of walking aids and activity and participation domains. Thirteen studies
      were included. Two studies involved canes, four pertained to rollators, and seven
      dealt with multiple types of walking aids. Mobility was the most frequently
      examined domain of activity and participation. Both negative and positive results
      were found. Negative outcomes were linked to the physical characteristics of the
      device, the use, environment, and personal reluctance. When incorporated in daily
      life, walking aids were found to enable several domains of activity and
      participation. Whether walking aids facilitate activity and participation may
      depend on the user's ability to overcome obstacles and integrate them in daily
      life. More high-quality research is needed to draw conclusions about their
      effectiveness.

PMID- 29176407
TI  - Cholesterol metabolism in humans: a review of methods and comparison of results.
AB  - PURPOSE OF REVIEW: Cholesterol metabolism has been the object of intense
      investigation for decades. This review focuses on classical and novel methods
      assessing in vivo cholesterol metabolism in humans. Two factors have fueled
      cholesterol metabolism studies in the last few years: the renewed interest in the
      study of reverse cholesterol transport (RCT) as an atheroprotective mechanism and
      the importance of the gut microbiome in affecting cholesterol metabolism. RECENT
      FINDINGS: Recent applications of these methods have spanned from the assessment
      of the effect on cholesterol synthesis, absorption or excretion of drugs (such as
      ezetimibe, PCSK9 inhibitors and plant sterols) and the gut microbiome to the more
      complex assessment of transintestinal cholesterol excretion (TICE) and RCT.
      SUMMARY: These methods continue to be a valuable tool to answer novel questions
      and investigate the complexity of in-vivo cholesterol metabolism.

PMID- 29176408
TI  - Prescription Opioid Use among Opioid-Naive Women Undergoing Immediate Breast
      Reconstruction.
AB  - BACKGROUND: Cancer patients may be particularly vulnerable to the deleterious
      effects of prolonged opioid use. The authors explored the factors that influence
      postoperative opioid prescription fills among women following postmastectomy
      reconstruction. METHODS: Using the Truven Health MarketScan Research Databases,
      the authors identified a cohort of 4113 opioid-naive patients undergoing
      mastectomy and immediate breast reconstruction between January of 2010 and August
      of 2014. Outcomes included average daily oral morphine equivalents and the
      incidence of prolonged opioid fills (between 90 and 120 days after surgery).
      Using multivariable regression, the authors examined the effect of patient
      demographic characteristics, reconstructive technique, comorbid medical and
      psychiatric conditions, and postoperative complications on outcome variables.
      RESULTS: In this cohort, 90 percent of patients filled opioid prescriptions
      perioperatively, and 10 percent continued to fill prescriptions beyond 3 months
      after surgery. Patients with depression were more likely to fill prescriptions of
      higher average daily oral morphine equivalents (74.2 mg versus 58.3 mg; p <
      0.01), and patients with anxiety were more likely to fill opioids for prolonged
      periods (13.4 percent versus 9.1 percent; p < 0.01). Patients undergoing
      autologous free flap reconstruction were less likely to fill prescriptions for a
      prolonged period following surgery (5.9 percent versus 10.2 percent; p < 0.001).
      CONCLUSIONS: Prescription opioid fills are common following breast
      reconstruction, and 10 percent of all patients continue to fill opioid
      prescriptions beyond 3 months after surgery. Prolonged fills are influenced by
      both patient factors and surgical procedure, and attention should be directed
      toward identifying opioid alternatives when possible. CLINCAL QUESTION/LEVEL OF
      EVIDENCE: Risk, III.

PMID- 29176409
TI  - Discussion: Revisiting the Abdominal Donor Site: Introducing a Novel Nomenclature
      for Autologous Breast Reconstruction.

PMID- 29176410
TI  - The Impact of Autologous Breast Reconstruction on Body Mass Index Patterns in
      Breast Cancer Patients: A Propensity-Matched Analysis.
AB  - BACKGROUND: Weight gain is common in breast cancer patients and increases the
      risk of recurrence and mortality. The authors assessed the impact of autologous
      breast reconstruction on body mass index patterns after diagnosis in mastectomy
      patients. METHODS: Women undergoing therapeutic mastectomy at the authors'
      institution from 2008 to 2010 were identified. Patients undergoing no breast
      reconstruction or autologous breast reconstruction were propensity-matched by age
      at diagnosis, baseline obesity, mastectomy laterality, and adjuvant therapies.
      Multivariable regression was used to estimate covariate associations with
      percentage body mass index change and percentage body mass index change greater
      than 5.0 percent at 1 to 4 years after diagnosis. RESULTS: Of 524 total patients,
      80 propensity-matched pairs were identified. In multivariable regression, women
      undergoing immediate autologous breast reconstruction had reduced body mass index
      changes after diagnosis, compared with nonreconstruction patients, at 1 year
      (beta = -5.25 percent; p < 0.01), 2 years (beta = -8.78 percent; p < 0.01), and 3
      years (beta = -7.21 percent; p < 0.01). After 4 years, all autologous
      reconstruction was predictive of reduced body mass index changes (beta = -3.54
      percent; p = 0.02). Higher body mass index increases were observed among women
      who were leaner at diagnosis (p < 0.01 at 1 year) and received chemotherapy (p =
      0.02 at 3 years; p = 0.04 at 4 years). CONCLUSIONS: Women undergoing autologous
      breast reconstruction gained less weight after diagnosis than nonreconstruction
      patients. Normal baseline body mass index and chemotherapy were predictive of
      greater body mass index increases. These findings may guide targeted weight
      management strategies in high-risk patients to maximize survival rates. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29176411
TI  - Evidence-Based Performance Measures: Quality Metrics for the Care of Patients
      Undergoing Breast Reconstruction.
AB  - The American Society of Plastic Surgeons commissioned the Breast Reconstruction
      Performance Measure Development Work Group to identify and draft quality measures
      for the care of patients undergoing breast reconstruction surgery. Two outcome
      measures were identified. The first desired outcome was to reduce the number of
      returns to the operating room following reconstruction within 60 days of the
      initial reconstructive procedure. The second desired outcome was to reduce flap
      loss within 30 days of the initial reconstructive procedure. All measures in this
      report were approved by the American Society of Plastic Surgeons Breast
      Reconstruction Performance Measures Work Group and the American Society of
      Plastic Surgeons Executive Committee. The Work Group recommends the use of these
      measures for quality initiatives, Continuing Medical Education, Maintenance of
      Certification, American Society of Plastic Surgeons' Qualified Clinical Data
      Registry reporting, and national quality reporting programs.

PMID- 29176412
TI  - Prospective Controlled Study of Chin Augmentation by Means of Fat Grafting.
AB  - BACKGROUND: Although fat grafting is a valuable tool for different areas of
      plastic surgery, its use in the chin area has never been evaluated. A variety of
      methods are available for adjusting suboptimal chin morphology, and they each
      present drawbacks. METHODS: A prospective controlled study was performed to
      evaluate whether fat grafting increases the chin volume and sagittal projection
      and to determine the magnitude and nature of the observed changes. Forty-two
      consecutive patients underwent chin augmentation by means of fat grafting between
      October of 2014 and January of 2016. All patient images were analyzed using a
      software program (Fiji package of ImageJ), which creates a three-dimensional
      version of the chin that is used to produce reliable estimates of the volume and
      gain in sagittal projection. RESULTS: All 42 patients showed an increase in the
      sagittal projection and total volume at 4 weeks and 6 months after surgery. The
      sagittal projection increased from 4 mm to 12 mm (average, 8.9 mm) and from 3 mm
      to 11 mm (average, 7 mm) after 4 weeks and 6 months, respectively. The total
      volume increase ranged from 3 to 11 ml (average, 8 ml) after 4 weeks and from 3
      to 8 ml (average, 7.4 ml) after 6 months. CONCLUSION: Fat grafting to the chin
      area is a reliable method for improving chin volumes (to a maximum of
      approximately 10 cc in our study) and sagittal projections (to a maximum of
      approximately 11 mm in our study). CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 29176413
TI  - Mentor Contour Profile Gel Implants: Clinical Outcomes at 10 Years.
AB  - BACKGROUND: Contour Profile Gel/MemoryShape breast implants consist of a textured
      silicone elastomer shell filled with silicone gel. The objective of this clinical
      study was to assess the safety and effectiveness of Contour Profile
      Gel/MemoryShape breast implants in women who were undergoing primary breast
      augmentation, primary breast reconstruction, or revision surgery (revision
      augmentation or revision-reconstruction). METHODS: This was a prospective, open
      label, multicenter clinical study involving Contour Profile Gel/MemoryShape
      breast implants in 955 female subjects, including 572 primary augmentation, 124
      revision-augmentation, 190 primary reconstruction, and 69 revision-reconstruction
      subjects. Safety was assessed based on the incidence, severity, and method of
      resolution of all complications. Endpoints were examined on both a per-subject
      and a per-implant basis. RESULTS: For the primary augmentation, revision
      augmentation, primary reconstruction, and revision-reconstruction cohorts, the
      Kaplan-Meier estimated 10-year cumulative incidence rates for the key
      complications at the subject level were as follows: Baker grade III/IV capsular
      contracture, 3.6 (primary augmentation), 15.5 (revision-augmentation), 14.3
      (primary reconstruction), and 16.4 (revision-reconstruction) percent; infection,
      0.7 (primary augmentation), 1.9 (revision-augmentation), 1.6 (primary
      reconstruction), and 2.9 (revision-reconstruction) percent; explantation with or
      without replacement, 9.2 (primary augmentation), 25.9 (revision-augmentation),
      34.1 (primary reconstruction), and 49.0 (revision-reconstruction) percent;
      explantation with replacement with study device, 4.0 (primary augmentation), 10.8
      (revision-augmentation), 16.7 (primary reconstruction), and 27.9 (revision
      reconstruction) percent; and any reoperation, 22.3 (primary augmentation), 35.0
      (revision-augmentation), 52.7 (primary reconstruction), and 59.7 (revision
      reconstruction) percent. CONCLUSION: The results of this study demonstrate that
      Contour Profile Gel/MemoryShape breast implants are safe and effective for
      primary and revision breast augmentation and reconstruction for women at least 22
      years old.

PMID- 29176414
TI  - Prospective, Double-Blind Evaluation of Umbilicoplasty Techniques Using
      Conventional and Crowdsourcing Methods.
AB  - BACKGROUND: Umbilical reconstruction is an important component of deep inferior
      epigastric perforator (DIEP) flap breast reconstruction. This study evaluated the
      aesthetics of three different umbilical reconstruction techniques during DIEP
      flap breast reconstruction. METHODS: From January to April of 2013, a total of 29
      consecutive patients undergoing DIEP flap breast reconstruction were randomized
      intraoperatively to receive one of three umbilicoplasty types: a diamond, an
      oval, or an inverted V incision. Independent plastic surgeons and members of the
      general public, identified using an online "crowdsourcing" platform, evaluated
      aesthetic outcomes in a blinded fashion. Reviewers were shown postoperative
      photographs of the umbilicus of all patients and a four-point Likert scale was
      used to rate the new umbilicus on the size, scar formation, shape, localization,
      and overall appearance. RESULTS: Results for the focus group of independent
      plastic surgeons and 377 members of the public were retrieved (n = 391). A total
      of 10 patients (34.5 percent) were randomized into having the diamond incision,
      10 (34.5 percent) had the oval incision, and nine (31.0 percent) had the inverted
      V incision. Patients were well matched in terms of overall characteristics. The
      general public demonstrated a significant preference for the oval incision in all
      five parameters. There was no preference identified among surgeons. CONCLUSION:
      This study provides evidence that a sample of the U.S. general public prefers the
      aesthetics of the oval umbilicoplasty incision, which contrasted with the lack of
      preference identified within this focus group of plastic surgeons. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 29176415
TI  - Discussion: Protective Effect of Hydrogen Gas Inhalation on Muscular Damage Using
      a Mouse Hindlimb Ischemia-Reperfusion Injury Model.

PMID- 29176416
TI  - Is Postoperative Intensive Care Unit Care Necessary following Cranial Vault
      Remodeling for Sagittal Synostosis?
AB  - BACKGROUND: Of U.S. craniofacial and neurosurgeons, 94 percent routinely admit
      patients to the intensive care unit following cranial vault remodeling for
      correction of sagittal synostosis. This study aims to examine the outcomes and
      cost of direct ward admission following primary cranial vault remodeling for
      sagittal synostosis. METHODS: An institutional review board-approved
      retrospective review was undertaken of the records of all patients who underwent
      primary cranial vault remodeling for isolated sagittal craniosynostosis from 2009
      to 2015 at a single pediatric hospital. Patient demographics, perioperative
      course, and outcomes were recorded. RESULTS: One hundred ten patients met
      inclusion criteria with absence of other major medical problems. Average age at
      operation was 6.7 months, with a mean follow-up of 19.8 months. Ninety-eight
      patients (89 percent) were admitted to a general ward for postoperative care,
      whereas the remaining 12 (11 percent) were admitted to the intensive care unit
      for preoperative or perioperative concerns. Among ward-admitted patients, there
      were four (3.6 percent) minor complications; however, there were no major adverse
      events, with none necessitating intensive care unit transfers from the ward and
      no mortalities. Average hospital stay was 3.7 days. The institution's financial
      difference in cost of intensive care unit stay versus ward bed was $5520 on
      average per bed per day. Omitting just one intensive care unit postoperative day
      stay for this patient cohort would reduce projected health care costs by a total
      of $540,960 for the study period. CONCLUSION: Despite the common practice of
      postoperative admission to the intensive care unit following cranial vault
      remodeling for sagittal craniosynostosis, the authors suggest that postoperative
      care be considered on an individual basis, with only a small percentage requiring
      a higher level of care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29176417
TI  - Discussion: A New Method for Reconstruction of Vermilion Deficiency in Cleft Lip
      Deformity: The Bi-Winged Myomucosa Switch Flap.

PMID- 29176418
TI  - Discussion: Concomitant Panniculectomy Affects Wound Morbidity but Not Hernia
      Recurrence Rates in Abdominal Wall Reconstruction: A Propensity Score Analysis.

PMID- 29176419
TI  - The Role of Checklists and Human Factors for Improved Patient Safety in Plastic
      Surgery.
AB  - LEARNING OBJECTIVES: After studying the article, participants should be able to:
      1. Describe the role of human factors and nontechnical skills for patient safety
      and recognize the need for customization of surgical checklists. 2. Apply
      encouragement to speaking up and understand the importance of patient involvement
      for patient safety. 3. Recognize the potential for improvement regarding patient
      safety in their own environment and take a leading role in the patient safety
      process. 4. Assess their own safety status and develop measures to avoid
      unnecessary distraction in the operating room. SUMMARY: Over the past 20 years,
      there has been increased attention to improving all aspects of patient safety
      and, in particular, the important role of checklists and human factors. This
      article gives a condensed overview of selected aspects of patient safety and aims
      to raise the awareness of the reader and encourage further study of referenced
      literature, with the goal of increased knowledge and use of proven safety
      methods. The CME questions should help indicate where there is still potential
      for improvement in patient safety, namely, in the field of nontechnical skills.

PMID- 29176420
TI  - Trends and Predictors of National Institutes of Health Funding to Plastic Surgery
      Residency Programs.
AB  - BACKGROUND: Recent studies have demonstrated low levels of National Institutes of
      Health funding for surgical research. The authors compared the funding in plastic
      surgery with the funding for other surgical specialties. METHODS: A query of
      National Institutes of Health grants awarded to departments of surgical
      specialties was performed using the National Institutes of Health RePORTER
      database (2008 to 2016). Trends in funding were compared by specialty and
      adjusted for the number of active physicians in each specialty. Plastic surgery
      residency program characteristics were correlated with funding procurement.
      RESULTS: Eight hundred eighty-nine faculty at 94 plastic surgery residency
      programs were queried. Forty-eight investigators (5.4 percent) at 23 programs
      (24.4 percent) had National Institutes of Health funding. From 2008 to 2016, a
      total of $84,142,138 was awarded through 81 grants. Funding supported
      translational (44.6 percent), clinical (26.4 percent), basic science (27.2
      percent), and educational (1.7 percent) research. In 2016, plastic surgery
      received the least amount of National Institutes of Health funding per active
      physician ($1,530) relative to orthopedic surgery ($3124), obstetrics and
      gynecology ($3885), urology ($5943), otolaryngology ($9999), general surgery
      ($11,649), ophthalmology ($11,933), and neurologic surgery ($20,874). Plastic
      surgery residency program characteristics associated with National Institutes of
      Health funding were high ranking and had more than 10 clinical faculty (p <
      0.05). CONCLUSIONS: Plastic surgery receives the least National Institutes of
      Health funding among the surgical specialties. Departments and divisions of
      plastic surgery should support investigators applying for research grants to
      increase future National Institutes of Health funding.

PMID- 29176421
TI  - Discussion: Trends and Predictors of National Institutes of Health Funding to
      Plastic Surgery Residency Programs.

PMID- 29176422
TI  - Revisiting the Fundamental Operative Principles of Plastic Surgery.

PMID- 29176425
TI  - Reply: Medial Row Perforators Are Associated with Higher Rates of Fat Necrosis in
      Bilateral DIEP Flap Breast Reconstruction.

PMID- 29176426
TI  - Reply: Direct-to-Implant Breast Reconstruction without the Use of an Acellular
      Dermal Matrix Is Cost Effective and Oncologically Safe.

PMID- 29176427
TI  - Principles of Cleft Lip Repair: Conventions, Commonalities, and Controversies.

PMID- 29176428
TI  - Heterogeneity assessment in gastroenterology systematic reviews: an analysis of
      current practices.
AB  - AIM: In systematic reviews and meta-analyses, variation (heterogeneity) in the
      primary studies is often a concern resulting from factors such as study design,
      data analysis methods, study quality, settings and interventions and/or patient
      characteristics. After determining the extent of heterogeneity, authors examine
      the causes of heterogeneity via sensitivity analysis, subgroup analysis and/or
      meta-regression analysis. There is no assessment of heterogeneity practices in
      gastroenterological literature; thus, we present this assessment. METHODS: We
      performed a PubMed search to identify systematic reviews published from 2011 to
      2016 in the top 10 gastroenterology journals, as well as gastrointestinal topics
      in general medical journals and the PROSPERO trial registry. The first and second
      authors independently abstracted data elements, such as levels of inconsistency,
      sensitivity analysis, subgroup analysis and meta-regression analysis. RESULTS:
      The search identified 3154 studies; of these, 337 were eligible for inclusion.
      Included studies consisted of 306 from the gastroenterology literature, 19
      studies from PROSPERO and 12 studies from the general internal medicine journals.
      A significant number of reviews in gastroenterology journals (31.05%, 95/306),
      internal medicine journals (16.67%, 2/12) and PROSPERO (52.63%, 10/19) conducted
      a meta-analysis despite having fewer than 10 primary studies. Most of the reviews
      in gastroenterology journals (81.05%, 248/306), general internal medicine
      journals (75%, 9/12) and PROSPERO results (73.68%, 14/19) used a combination of
      methods to assess heterogeneity. There were 20 various definitions of levels of
      inconsistency (I) throughout all the results. Random effects was the most common
      model choice in gastroenterology journals reviews (57.84%; 177/306), internal
      medicine journals (75%, 9/12) and for PROSPERO results (41.11%, 8/19). The
      majority of reviews did not discuss the impact of heterogeneity on results in the
      gastroenterology journals (62.09%, 190/306), only one study in the general
      internal medicine journals and only one study in the PROSPERO results.
      CONCLUSION: In gastroenterology journals and other journals printing
      gastrointestinal topic systematic reviews, most conducted statistical tests for
      heterogeneity; however, the statistical methods could be more robust and the
      impact of heterogeneity discussed more often in the article.

PMID- 29176429
TI  - Identifying and classifying indicators affected by performing clinical pathways
      in hospitals: a scoping review.
AB  - AIM: To analyse the evidence regarding indicators affected by clinical pathways
      (CPW) in hospitals and offer suggestions for conducting comprehensive systematic
      reviews. METHODS: We conducted a systematic scoping review and searched the
      Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus,
      OVID, Science Direct, ProQuest, EMBASE and PubMed. We also reviewed the reference
      lists of included studies. The criteria for inclusion of studies included
      experimental and quasi-experimental studies, implementing CPW in secondary and
      tertiary hospitals and investigating at least one indicator. Quality of included
      studies was assessed by two authors independently using the Critical Appraisal
      Skills Program for clinical trials and cohort studies and the Joanna Briggs
      Institute Critical Appraisal Tool for Quasi-Experimental Studies. RESULTS: Forty
      seven out of 2191 studies met the eligibility and inclusion criteria. The
      majority of included studies had pretest-posttest quasi-experimental design and
      had been done in developed countries, especially the United States. The
      investigation of evidence resulted in identifying 62 indicators which were
      classified into three categories: input indicators, process and output indicators
      and outcome indicators. Outcome indicators were more frequent than other
      indicators. Complication rate, hospital costs and length of hospital stay were
      dominant in their own category. Indicators such as quality of life and adherence
      to guidelines have been considered in studies that were done in recent years.
      CONCLUSION: Implementing CPW can affect different types of indicators such as
      input, process, output and outcome indicators, although outcome indicators
      capture more attention than other indicators. Patient-related indicators were
      dominant outcome indicators, whereas professional indicators and organizational
      factors were considered less extensively. WHAT IS KNOWN ABOUT THE TOPIC?: WHAT
      DOES THIS ARTICLE ADD?

PMID- 29176430
TI  - The role of N-methyl-D-aspartate receptors and metabotropic glutamate receptor 5
      in the prepulse inhibition paradigms for studying schizophrenia: pharmacology,
      neurodevelopment, and genetics.
AB  - Treatments for the positive and negative symptoms of schizophrenia have been
      explored for decades, but no completely successful therapy has been found as yet.
      Metabotropic glutamate receptor 5 (mGluR5), which potentiates N-methyl-D
      aspartate receptors in brain regions implicated in schizophrenia, has become a
      novel drug target in the treatment of schizophrenia, especially for the mGluR5
      positive allosteric modulators. Individuals with schizophrenia show deficits in
      prepulse inhibition (PPI), which is an operational measurement of sensorimotor
      gating. In this review, we focus on pharmacological, neurodevelopmental, and
      genetic animal models of disrupted PPI, with the aim of showing the potential
      role of mGluR5 in modulating the activity of N-methyl-D-aspartate receptors and
      their contributions toward the treatment of schizophrenia. As, the impairment of
      attentional modulation of PPI, but not that of baseline PPI, in individuals with
      schizophrenia is correlated with their symptom severity, this review also
      highlights that investigation of attentional modulation of PPI is critical for
      studying both cognitive impairments and glutamatergic dysfunctions of
      schizophrenia.

PMID- 29176432
TI  - Gun laws in the United States.

PMID- 29176431
TI  - Utilizing gnotobiotic models to inform the role of the microbiome in vaccine
      response heterogeneity.
AB  - PURPOSE OF REVIEW: Gnotobiotic models have the potential to provide substantial
      insight into how the microbiome shapes its host's response to vaccines. This
      review aims to summarize literature about the role of the microbiome in shaping
      the immune system and vaccine response heterogeneity, summarize gnotobiotic and
      other murine models that help us understand the immune system and vaccine
      response, and suggest novel ways that these models could be used to further
      understand vaccine response heterogeneity. RECENT FINDINGS: Clinical data have
      suggested that numerous vaccines' effectiveness are regulated by the microbiome
      and often correlate with the abundance of specific taxa. Gnotobiotic and other
      animal models are beginning to illuminate the complex effects induced by the
      presence of particular microbial groups and communities. Such models have
      identified microbial groups that improve vaccine response to rotavirus vaccine
      and identified pathways by which the microbiome influences response to influenza
      and other vaccines. SUMMARY: By applying a range of vaccines across gnotobiotic
      mouse models, researchers may be able to identify the effects of single
      microorganisms as well as interacting communities of microorganisms on the immune
      response.

PMID- 29176434
TI  - Drug updates and approvals: 2017 in review.

PMID- 29176433
TI  - Drug updates and approvals: 2017 in review.
AB  - In 2017, the FDA approved several new drugs for use in primary care. This article
      highlights the following new drugs: brodalumab (Siliq), dapagliflozin and
      saxagliptin (Qtern), dupilumab (Dupixent), oxymetazoline (Rhofade), safinamide
      (Xadago), and sarilumab (Kevzara).

PMID- 29176436
TI  - Responding to child sexual abuse disclosure.

PMID- 29176435
TI  - Responding to child sexual abuse disclosure.
AB  - In cases of child sexual abuse (CSA), NPs are faced with a variety of options
      dictated by community, agency, and individual resources. This article looks at
      victim-centered care from current guidelines and offers resources for clinical
      practice decision making when responding to CSA disclosure.

PMID- 29176437
TI  - Anticoagulant options in atrial fibrillation: When new treatments become standard
      practice.
AB  - Direct oral anticoagulants (DOACs) have expanded options for treating patients
      with atrial fibrillation (AF). However, DOACs are not warfarin substitutes, and
      NPs need to be aware of the difference. DOACs are first-line agents when treating
      AF, yet warfarin has not been replaced. Individualized patient characteristics
      drive current guidelines.

PMID- 29176438
TI  - Delirium monitoring and management in the acute care setting.
AB  - Associated with substantial morbidity and mortality, delirium is a syndrome
      commonly experienced by hospitalized adults. This article presents a case study
      highlighting how delirium may go unrecognized by the healthcare team and provides
      10 suggestions for improving delirium assessment, prevention, and management in
      the acute care setting.

PMID- 29176439
TI  - The menopausal woman: The need for an individualized plan of care.
AB  - With life expectancy increasing, women will spend one-third of their lives in and
      beyond menopause. A collaborative discussion with the clinician facilitates
      informed decision-making and should include evidence-based discussion of
      physiologic changes, assessment of symptoms and treatment options, review of
      screening recommendations, and discussion of disease risk-reduction strategies
      and psychosocial issues.

PMID- 29176440
TI  - The STEADI toolkit: Incorporating a fall prevention guideline into the primary
      care setting.
AB  - Falls are a growing problem in the older adult population, leading to
      debilitating and traumatic consequences. The CDC's STEADI toolkit was created to
      assist providers in screening and managing falls. This article introduces the
      toolkit and examines the process and importance of adopting it into routine
      clinical practice.

PMID- 29176442
TI  - Factors Associated With Removal of Urinary Catheters After Surgery.
AB  - Publicly available data from the Centers for Medicaid & Medicare Services were
      used to analyze factors associated with removal of the urinary catheter within 48
      hours after surgery in 59 Massachusetts hospitals. Three factors explained 36% of
      the variance in postoperative urinary catheter removal: fewer falls per 1000
      discharges, better nurse-patient communication, and higher percentage of Medicare
      patients. Timely urinary catheter removal was significantly greater in hospitals
      with more licensed nursing hours per patient day.

PMID- 29176443
TI  - Levosimendan enhances memory through antioxidant effect in rat model: behavioral
      and molecular study.
AB  - Impairment of learning and memory has been associated with accumulation of
      reactive oxygen species in the body. It has also been found that antioxidants
      enhance learning and memory. Levosimendan is a cardiac inotropic and vasodilator
      agent that has pleotropic effects including antioxidant, anti-inflammatory, and
      smooth muscle vasodilatory actions. In this study, we investigated the effect of
      levosimendan on learning and memory in rats. Levosimendan (12 ug/kg,
      intraperitoneally) or vehicle was administered once a week for 8 weeks. The
      radial arm water maze was used to assess spatial learning and memory. In
      addition, hippocampus levels of antioxidant biomarkers/enzyme - reduced
      glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione
      peroxidase, superoxide dismutase, catalase, and thiobarbituric acid reactive
      substance - were assessed. Levosimendan significantly enhanced short-term (30
      min) and long-term (5 h) memory. Levosimendan also significantly increased levels
      of glutathione peroxidase and GSH and decreased thiobarbituric acid reactive
      substance. There were no significant effects on the level of other oxidative
      stress biomarkers. In conclusion, levosimendan enhanced short-term and long-term
      memory by potentiating antioxidant defense mechanism in the hippocampus.

PMID- 29176444
TI  - Comprehensive Next-Generation Sequencing Analysis is Recommended for the
      Management of Patients With Melanoma.

PMID- 29176445
TI  - New thinking on gonorrhoea control in MSM: are antiseptic mouthwashes the answer?
AB  - PURPOSE OF REVIEW: The rate of gonorrhoea is rising and is much higher in men who
      have sex with men (MSM) than heterosexuals. The purpose of this review was to
      describe research supporting a new paradigm of transmission of gonorrhoea in MSM
      and interventions that may result from this. RECENT FINDINGS: Evidence is
      accumulating that gonorrhoea in MSM is transmitted differently than previously
      thought and that asymptomatic sites of infection may play a major role in the
      persistent of gonorrhoea at a population level. Saliva commonly contains
      gonorrhoea, and saliva is commonly used during sexual acts. Both in-vitro, in
      vivo studies have suggested that antibacterial mouthwash may reduce gonorrhoea at
      the oropharynx. A recently published mathematical model also suggests that if
      mouthwash were effective, it would result in considerable declines in the
      community prevalence in MSM. SUMMARY: A newly suggested paradigm for the
      transmission of gonorrhoea in MSM could potentially offer a simple condom-free
      control strategy. But considerable more research is required before it could be
      recommended even if it were shown to be effective in a clinical trial.

PMID- 29176446
TI  - Addressing unhealthy alcohol use among people living with HIV: recent advances
      and research directions.
AB  - PURPOSE OF REVIEW: Unhealthy alcohol use is prevalent among people living with
      HIV (PLWH). We sought to identify the most current literature examining the
      impact of unhealthy alcohol on health outcomes and latest developments on how to
      best intervene. RECENT FINDINGS: New research shows that PLWH have heightened
      morbidity and mortality at lower levels of alcohol consumption compared with HIV
      uninfected persons. Studies published since 2016 have further elucidated the
      effects of persistent unhealthy alcohol use on HIV treatment outcomes over time.
      Screening and brief interventions, as well as pharmacologic treatment, can reduce
      unhealthy alcohol use among PLWH. SUMMARY: Unhealthy alcohol use is an important
      and modifiable risk factor for poor health and HIV treatment outcomes among PLWH.
      More research is needed to encourage and maintain engagement in alcohol-related
      interventions and improve implementation.

PMID- 29176447
TI  - Pattern of Methamphetamine Use and the Time Lag to Methamphetamine Dependence.
AB  - OBJECTIVES: Use of methamphetamine (MA) commonly co-occurs with the use of other
      substances. The present study aims to examine substance initiation patterns of
      other substances, including alcohol, nicotine, inhalants, and cannabis (OTH), in
      MA users and its consequence on the time lag of MA dependence. METHODS:
      Sociodemographic, environmental, and clinical data were obtained from MA users at
      a Thai substance treatment center. The Semi-Structured Assessment for Drug
      Dependence and Alcoholism was employed to diagnose drug dependence. RESULTS: Of
      991 MA users, 52.6% were males, and the average age was 26.8 +/- 7.1 years. The
      mean age of first MA use (18 years) was greater than the mean age of first use of
      alcohol (17 years), nicotine (16 years), and inhalants (15 years) (P < 0.001),
      but was comparable with the mean age at the first use of cannabis (P > 0.05).
      Family history of MA use and nicotine dependence were associated with early MA
      onset. Participants who used MA as their first drug (MA>OTH) were more likely to
      be female and less likely to smoke intensely and to be exposed to severe
      traumatic events than those who used MA later than other substances (OTH>MA). The
      time lag from age at onset of MA use to MA dependence was shorter in OTH>MA than
      in MA>OTH (3 vs 5 years; chi = 5.7, P = 0.02, log-rank test). CONCLUSIONS: A
      higher proportion of women was observed in MA>OTH than in OTH>MA. The use of
      other substances before MA increases the individual's vulnerability in shortening
      the interval between age at onset of MA use and MA dependence in a substance
      treatment cohort.

PMID- 29176448
TI  - Patients' Experiences of Using a Cellular Photo Digital Breathalyzer for
      Treatment Purposes.
AB  - OBJECTIVES: The field of eHealth systems is rapidly developing and is now
      expanding into alcohol treatment settings. Despite a growing public and
      professional interest, cellular photo digital breathalyzers (CPDBs) have not been
      investigated in a clinical context so far. In this study, we aimed to investigate
      the experiences of patients in alcohol treatment who had been using a CPDB
      TripleA- for a minimum of three months. What are their personal experiences of
      using the CPDB? Do the patients think it supports them to change their drinking
      habits, and if so, in what way? METHODS: A qualitative interview study with
      individuals who had been using the CPDB TripleA, for at least 3 months as
      complement to treatment (12-step program or hospital-based outpatient care). A
      thematic analysis with an inductive approach was used to identify, analyze, and
      interpret patterns within data. RESULTS: In all, 12 interviews were conducted
      with 8 men and 4 women. Participants were generally enthusiastic about the CPDB
      and found it convenient and useful, even though it created a need for privacy
      when using the device. Although technical problems were substantial, participants
      were tolerant to those. The system was perceived to support self-control and to
      restore relations, but did not replace the need for close contact with
      caregivers. Self-motivation to change drinking habits was essential, and could
      not be reached by solely using the CPDB. CONCLUSIONS: Participants perceived the
      CPDB as a convenient and useful tool that was supportive under the circumstances
      that it was used in a context that included personal contact with a caregiver;
      and the user felt more than just a minimum of motivation to reduce drinking.
      Technical stability needs to be achieved to secure long-term use.

PMID- 29176449
TI  - Can Appropriate Systemic Treatment Help Protect the Cornea in Patients With
      Rheumatoid Arthritis? A Multidisciplinary Approach to Autoimmune Ocular
      Involvement.
AB  - PURPOSE: To correlate rheumatologic with ophthalmic and laboratory findings in
      patients with rheumatoid arthritis (RA) to identify what effect these have on
      development of ocular disease. METHODS: This is a cross-sectional study of 172
      eyes of 86 patients with RA. Patients were examined by a group of
      rheumatologists. Sociodemographic, clinical, and laboratory data were collected.
      All patients underwent complete ophthalmologic examination including corneal
      topography and endothelial cell count. RESULTS: There was no significant
      correlation between RA-negative prognostic indicators (NPIs) and pathologic
      corneal findings. Patients using disease-modifying antirheumatic drugs (DMARDs)
      and antimalarial drugs had greater corneal volumes (mean difference 8.51 mm, 90%
      confidence interval [CI], 3.98-13.04, P = 0.004; and 2.24, 90% CI, 0.32-4.54, P =
      0.048, respectively). Patients using azathioprine had lower endothelial cell
      counts compared with those using other drugs (mean difference 180 cells/mm, 90%
      CI, 69-291, P = 0.008). Patients using biologic DMARDs had better tear osmolarity
      values (between 280 and 300 mOsm/L) than patients not using them (mean difference
      14.3 mOsm/L, P = 0.022). There was no correlation between NPIs of RA and positive
      keratoconus screening indices (Spearman correlation OD -0.013, P = 0.91; OS 
      0.033, P = 0.76). CONCLUSIONS: There was no clear correlation between RA-NPIs and
      pathologic corneal findings in our study. DMARDs treatment may help maintain
      corneal integrity in our patients and prevented collagenolytic manifestations of
      RA. Other medications such as azathioprine should be used carefully, as
      endothelial damage may potentially occur.

PMID- 29176450
TI  - Corneal Cross-Linking With Verteporfin and Nonthermal Laser Therapy.
AB  - PURPOSE: To test whether verteporfin with a nonthermal laser increases corneal
      mechanical stiffness and resistance to enzymatic degradation ex vivo. METHODS:
      Thirty human corneas (n = 5 per group) were treated with verteporfin alone (V),
      irradiated with nonthermal laser therapy (689 nm) alone (NTL), or received
      combined treatment of verteporfin with nonthermal laser therapy for 1 sequence
      (V+NTL1) or 6 sequences (V+NTL6) of 1 minute of NTL exposure. Positive controls
      were pretreated with 0.1% riboflavin/20% dextran every 3 to 5 minutes for 30
      minutes and irradiated with ultraviolet light type A (lambda = 370 nm, irradiance
      = 3 mW/cm) for 30 minutes using the Dresden protocol (R+UVA). Untreated corneas
      were used as negative controls. The corneal biomechanical properties were
      measured with enzymatic digestion, compression, creep, and tensile strength
      testing. RESULTS: V+NTL6- and R+UVA-treated corneas acquired higher rigidity and
      more pronounced curvature than untreated corneas. The stress-strain tests showed
      that V+NTL6 and R+UVA corneas became significantly stiffer than controls (P <
      0.005). The V+NTL6 group seemed to be slightly stiffer than the R+UVA group,
      although the differences were not statistically significant. V+NTL6 corneas were
      found to have a significantly lower absolute creep rate (-1.87 vs. -3.46, P <
      0.05) and significantly higher maximum stress values (7.67 vs. 3.02 P < 0.05)
      compared with untreated corneas. CONCLUSIONS: Verteporfin-NTL (V+NTL6) increases
      corneal mechanical stiffness and resistance to enzymatic collagenase degradation.
      Although a clinical study is needed, our results suggest that V+NTL6 induces
      corneal cross-linking and corneal biomechanical changes that are similar to those
      induced by standard corneal collagen cross-linking.

PMID- 29176451
TI  - Comparison of Pterygium Recurrence Rates Among Different Races and Ethnicities
      After Primary Pterygium Excision by Surgeons in Training.
AB  - PURPOSE: To evaluate the impact of race and ethnicity, surgical technique, and
      level of surgeon training on recurrence rates after primary pterygium excision.
      METHODS: A retrospective review of patients who underwent primary pterygium
      excision at our academic institution was performed. The surgical technique
      conjunctival autografting (CAG) or amniotic membrane grafting (AMG)-was chosen at
      the attending surgeon's discretion, and all surgeries were performed by surgeons
      in training. The primary outcome measure was pterygium recurrence, defined as
      regrowth of fibrovascular tissue onto a clear cornea in the region of previous
      pterygium removal. RESULTS: There was a significant difference in age at
      presentation between white (64.3 +/- 11.4), Hispanic (50.0 +/- 13.5), black (64.8
      +/- 14.5), and Asian (59.3 +/- 9.2) patients (P < 0.001). Average time to
      recurrence was 4.4 +/- 3.0 months and was similar between races (P = 0.98). There
      was a significant difference in recurrence rates between the white (13%),
      Hispanic (28%), black (33%), and Asian (0%) patients (P = 0.049). Over 12 months,
      a significant difference in cumulative proportion with recurrence after AMG
      versus CAG was observed in Hispanic (75% vs. 30%; P = 0.002) and black (100% vs.
      42%; P = 0.001) patients. Sex, method of graft fixation (glue, suture, or both),
      and level of surgeon training showed no difference in pterygium recurrence (P >
      0.05). CONCLUSIONS: Hispanic and black patients are more likely to experience
      pterygium recurrence after AMG than CAG. White patients are less likely than
      Hispanic or black patients to experience recurrence regardless of the surgical
      technique. To reduce the likelihood of recurrence, surgeons may consider race and
      ethnicity when selecting their operative technique.

PMID- 29176452
TI  - Collagen-Based Fillers as Alternatives to Cyanoacrylate Glue for the Sealing of
      Large Corneal Perforations.
AB  - PURPOSE: To describe the use of collagen-based alternatives to cyanoacrylate glue
      for the sealing of acute corneal perforations. METHODS: A collagen analog
      comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG)
      and its chemical crosslinker were tested for biocompatibility. These CLP-PEG
      hydrogels, which are designed to act as a framework for corneal tissue
      regeneration, were then tested as potential fillers in ex vivo human corneas with
      surgically created full-thickness perforations. Bursting pressures were measured
      in each of 3 methods (n = 10 for each condition) of applying a seal: 1)
      cyanoacrylate glue with a polyethylene patch applied ab externo (gold standard);
      2) a 100-MUm thick collagen hydrogel patch applied ab interno, and 3) the same
      collagen hydrogel patch applied ab interno supplemented with CLP-PEG hydrogel
      molded in situ to fill the remaining corneal stromal defect. RESULTS:
      Cyanoacrylate gluing achieved a mean bursting pressure of 325.9 mm Hg,
      significantly higher than the ab interno patch alone (46.3 mm Hg) and the ab
      interno patch with the CLP-PEG filler (86.6 mm Hg). All experimental perforations
      were sealed effectively using 100 MUm hydrogel sheets as an ab interno patch,
      whereas conventional ab externo patching with cyanoacrylate glue failed to
      provide a seal in 30% (3/10) cases. CONCLUSIONS: An ab interno patch system using
      CLP-PEG hydrogels designed to promote corneal tissue regeneration may be a viable
      alternative to conventional cyanoacrylate glue patching for the treatment of
      corneal perforation. Further experimentation and material refinement is required
      in advance of clinical trials.

PMID- 29176453
TI  - Role of Confocal Microscopy in the Diagnosis of Pythium insidiosum Keratitis.
AB  - PURPOSE: To investigate the role of in vivo confocal microscopy for detection of
      Pythium insidiosum keratitis. METHODS: Medical records and confocal microscopy
      findings of 20 patients (21 eyes) with culture- or polymerase chain reaction
      proven P. insidiosum keratitis diagnosed at the Khon Kaen University Eye Center
      from January 2009 to December 2015 were retrospectively reviewed. Confocal
      microscopy was performed using Nidek ConfoScan 4. The images from 21 eyes with P.
      insidiosum keratitis and 4 other fungal keratitides were analyzed visually for
      morphology of the hyphae and special characteristics that would enable physicians
      to distinguish P. insidiosum keratitis from other fungal keratitides. RESULTS: A
      total of 21 eyes of 20 patients were included in the study. Fourteen (70%) were
      men, and 6 (30%) were women. In vivo confocal microscopy was able to identify
      hyphae in 20 of 21 eyes (95%). Beaded string-like hyperreflective branching
      structures with mean branching angles at 78.6 degrees or thin hyperreflective
      long lines were found in confocal microscopy findings of P. insidiosum keratitis.
      The diameter of the hyphae varied from 1.5 to 7.5 MUm. CONCLUSIONS: P. insidiosum
      keratitis is a severe progressive infectious corneal disease that causes vision
      loss in most patients. Confocal microscopy may provide rapid in vivo
      visualization of P. insidiosum hyphae in corneal tissues, but it cannot
      distinguish P. insidiosum from other fungal keratitides. Culture identification
      with zoospore induction or polymerase chain reaction remains the most reliable
      means to confirm the diagnosis of P. insidiosum keratitis.

PMID- 29176454
TI  - Pythium Insidiosum Keratitis: Histopathology and Rapid Novel Diagnostic Staining
      Technique.

PMID- 29176455
TI  - Reply.

PMID- 29176456
TI  - Appropriate use of laboratory test requests in the emergency department: a
      multilevel intervention.
AB  - OBJECTIVE: Laboratory test requests in the emergency department (ED) are
      increasing worldwide. We evaluated whether a multilevel intervention on the basis
      of the optimization of test profiles and educational meetings with physicians
      could reduce the number of tests ordered. PATIENTS AND METHODS: In a single
      center before and after study design, the 8-month intervention period was
      compared with the 8-month preintervention period. Laboratory test profiles were
      reduced from 6 to 2 and the number of tests in each profile was reduced by 50%.
      All physicians received education about the costs and appropriate use of the
      tests. Primary outcomes were the number of laboratory blood tests and their
      costs, with a focus on high-cost tests. Secondary outcomes were ED and laboratory
      performances (patients' waiting time, number of deaths in ED, re-entry,
      laboratory turn-around time, and add-on tests). RESULTS: Overall, 61 976 and 61
      154 patients were evaluated, respectively, during the intervention and the
      preintervention period. Laboratory blood test requests were decreased by 207 637
      (-36.3%) in the intervention period (P<0.05), which corresponds to a reduction of
      337.3 tests/100 patients. Costs were decreased by 608 079&OV0556; (-29.6%,
      P<0.05), leading to a cost reduction of 981.2&OV0556;/100 patients. High-cost
      test requests decreased by 11 457 (-27.3%) and contributed toward the overall
      reduction in costs with 197 206&OV0556; (-30.5%). No significant differences were
      found in ED and laboratory performances between intervention and preintervention
      periods. CONCLUSIONS: Optimization of test profiles and education on the costs
      and appropriate use of the tests significantly reduced laboratory test ordering
      and costs without affecting ED and laboratory performances.

PMID- 29176457
TI  - A-Frame free Vascularized Fibular Graft and Femoral Lengthening for Osteosarcoma
      Pediatric Patients.
AB  - BACKGROUND: Pediatric limb reconstruction after resection of a malignant tumor
      presents specific challenges. Multiple surgical techniques have been used to
      treat these patients. This paper describes a staged surgical technique for the
      reconstruction of large distal femoral defects due to tumor resection in
      skeletally immature patients. METHODS: Three pediatric patients with osteosarcoma
      of the distal femur underwent staged reconstruction. Neoadjuvant chemotherapy was
      followed by en bloc tumor resection and immediate reconstruction of the distal
      femoral defect with a vascularized free fibular autograft utilizing a unique A
      frame construct combined with intramedullary nail fixation. The second stage was
      a planned gradual lengthening of the healed construct, over a custom-made
      magnetically driven expandable intramedullary nail. RESULTS: All patients
      achieved bony union and satisfactory length with minimal complications. The
      patients all returned to full, unlimited physical activities. CONCLUSIONS: The
      early results confirm that the described technique is a safe and reliable
      procedure for the reconstruction of large femoral defects in pediatric patients
      with osteosarcoma. LEVEL OF EVIDENCE: Level IV-therapeutic.

PMID- 29176458
TI  - From the Editor.

PMID- 29176459
TI  - Patient, Primary Care Provider, and Specialist Perspectives on Specialty Care
      Coordination in an Integrated Health Care System.
AB  - Successful coordination of specialty care requires understanding the perspectives
      of patients, primary care providers, and specialists-that is, the specialty care
      "triad." This study used qualitative methods to compare these perspectives in an
      integrated health care system, using diabetes specialty care as an exemplar.
      Primary care providers and endocrinologists relied on interclinician
      relationships to coordinate care. Clinicians rarely included patients or other
      staff in their conceptualization of specialty care coordination. Patients often
      assumed responsibility for specialty care coordination but struggled to succeed.
      We identified several opportunities to improve coordination across the triad. In
      an integrated medical system, the shared organizational structure can facilitate
      these efforts.

PMID- 29176460
TI  - Primary Care and the Hypertension Care Continuum in Brazil.
AB  - This study provides estimates of hypertension prevalence, awareness, treatment,
      and control in Brazil and assesses how well different modes of primary care
      delivery achieve each of these outcomes. Over one-third of the Brazilian adult
      population had measured hypertension or prior diagnosis. Nearly 90% of these had
      recent contact with the health system, but only 65% were aware of their
      condition. Only 62% of these regularly sought care for hypertension, but of these
      92% received treatment. Hypertension control was 33% overall, but increased to
      57% among those who received all levels of care.

PMID- 29176461
TI  - Impact of Hydroxyurea on Anthropometry and Serum 25-Hydroxyvitamin D Among
      Children With Sickle Cell Disease.
AB  - OBJECTIVE: To evaluate the impact of hydroxyurea (HU) on nutritional status and
      serum 25-hydroxyvitamin D (25-OHD) of children with sickle cell disease (SCD).
      DESIGN: Anthropometry and serum 25-OHD were determined in 98 children with SCD,
      comprising of 68 in HU-group and 30 in HU-naive group. RESULTS: Underweight was
      more common among HU-naive group (33.3% vs. 10.3%, P=0.009), while 79.4% of HU
      group against 56.7% HU-naive had normal body mass index percentile for age and
      sex, P=0.028. None of the HU-group compared with 13.3% of the HU-naive had severe
      vitamin D deficiency, P=0.002. The mean 25-OHD of the HU-group was also higher
      (24.1+/-1.2 vs. 19.1+/-9.8 ng/mL, P=0.007). CONCLUSIONS: HU possibly ameliorate
      growth retardation and vitamin D deficiency in children with SCD.

PMID- 29176463
TI  - Primary Ewing Sarcoma of the Mastoid: A Novel Case Mimicking Acute Mastoiditis.
AB  - Ewing sarcoma (EWS) is a primitive neuroectodermal tumor arising in bone or soft
      tissue. It is the second most common primary bone malignancy of children and
      adolescents, with a peak incidence in the second decade of life. It most often
      arises in the long bones of the extremities and pelvis. Here, we present a novel
      case of EWS arising from the mastoid bone in a 5-year-old African American male
      who presented with symptoms of acute mastoiditis. This unique presentation
      highlights the importance of considering EWS in a patient who presents with
      atypical mastoiditis or a rapidly growing mass in the postauricular region.

PMID- 29176462
TI  - Feasibility and Acceptability of Internet-delivered Cognitive Behavioral Therapy
      for Chronic Pain in Adolescents With Sickle Cell Disease and Their Parents.
AB  - Pain is a clinical hallmark of sickle cell disease (SCD), and is rarely optimally
      managed. Cognitive-behavioral therapy (CBT) for pain has been effectively
      delivered through the Internet in other pediatric populations. We tested
      feasibility and acceptability of an Internet-delivered CBT intervention in 25
      adolescents with SCD (64% female, mean age=14.8 y) and their parents randomized
      to Internet CBT (n=15) or Internet Pain Education (n=10). Participants completed
      pretreatment/posttreatment measures. Eight dyads completed semistructured
      interviews to evaluate treatment acceptability. Feasibility indicators included
      recruitment and participation rates, engagement and adherence to intervention,
      and completion of outcome measures. In total, 87 referrals were received from 9
      study sites; our recruitment rate was 60% from those families approached for
      screening. Among participants, high levels of initial intervention engagement
      (>90%), and adherence (>70%) were demonstrated. Most participants completed
      posttreatment outcome and diary measures (>75%). Retention at posttreatment was
      80%. High treatment acceptability was reported in interviews. Our findings
      suggest that Internet-delivered CBT for SCD pain is feasible and acceptable to
      adolescents with SCD and their parents. Engagement and adherence were good. Next
      steps are to modify recruitment plans to enhance enrollment and determine
      efficacy of Internet CBT for SCD pain in a large multisite randomized controlled
      trial.

PMID- 29176464
TI  - A Giant Ear!
AB  - A 17 year old female presented with a progressive swelling on the left pinna for
      2 years. On examination the left pinna was enlarged and a pulsatile swelling was
      felt with an audible bruit. A diagnosis of arteriovenous malformation was
      confirmed by an angiography which revealed primary feeding vessel from the post
      auricular artery. The vessel was embolized and the mass excised.

PMID- 29176465
TI  - Can Pediatric Risk of Mortality Score (PRISM III) Be Used Effectively in Initial
      Evaluation and Follow-up of Critically Ill Cancer Patients Admitted to Pediatric
      Oncology Intensive Care Unit (POICU)? A Prospective Study, in a Tertiary Cancer
      Center in Egypt.
AB  - Pediatric Risk of Mortality Score (PRISM III-12) is a physiology-based predictor
      for risk of mortality. We conducted prospective study from January 1, 2014 to
      2015 in pediatric oncology intensive care unit (POICU) at South Egypt Cancer
      Institute, Egypt to explore the ability of 1st PRISM III-12 to predict the risk
      of mortality in critically ill cancer patients and the ability of serial PRISM
      III measured every 72 hours to follow-up the patients' clinical condition during
      POICU stay. In total, 123 (78 males) children were included. Median age was 5
      years (1 to 15 y). Death rate was 20%. 1st PRISM III-12 mean was 19 (0 to 61).
      The mean 1st PRISM III-12 for survivors was significantly higher compared with
      nonsurvivors (15 vs. 37 respectively; P<0.001). 1st PRISM III-12 mean was
      significantly correlated to the reasons for admission and organ failures' number
      (P<0.001 and <0.001). 1st PRISM III-12 correlated weakly positive with the length
      of stay (r=0.2; P=0.024). Receiver operator curve for 1st PRISM III-12 was 0.913
      (95% confidence interval, 0.85-0.98; P<0.001). Decline in serial PRISM III was
      significantly correlated with favorable (survivor) outcome (P<0.001). We
      concluded that PRISM III-12 can be used effectively in predicting the risk of
      mortality and following the clinical condition of patients during POICU stay.

PMID- 29176466
TI  - The Challenge of Next Generation Sequencing in a Boy With Severe Mononucleosis
      and EBV-related Lymphoma.
AB  - A severe course of infectious mononucleosis should always lead up to the
      suspicion of a primary immunodeficiency. We describe the case of a boy with
      severe mononucleosis accompanied by the development of hemophagocytic
      lymphohistiocytosis and lymphoma. By whole exome sequencing, we identified a
      mutation of uncertain significance in CTPS2, a gene closely related to CTPS1,
      which is involved in a primary immune deficiency with susceptibility to
      herpesviruses. We discuss the challenge of a correct interpretation of data from
      whole exome sequencing, questioning whether the CTPS2 variant found in our
      patient is just an incidental finding or a mutation with variable penetrance.

PMID- 29176467
TI  - Quantitative Imaging in the Abdomen.

PMID- 29176469
TI  - Diffusion Quantification in Body Imaging.
AB  - Diffusion-weighted imaging (DWI) is increasingly incorporated into routine body
      magnetic resonance imaging protocols. DWI can assist with lesion detection and
      even in characterization. Quantitative DWI has exhibited promise in the
      discrimination between benign and malignant pathology, in the evaluation of the
      biologic aggressiveness, and in the assessment of the response to treatment.
      Unfortunately, inconsistencies in DWI acquisition parameters and analysis have
      hampered widespread clinical utilization. Focusing primarily on liver
      applications, this article will review the basic principles of quantitative DWI.
      In addition to standard mono-exponential fitting, the authors will discuss
      intravoxel incoherent motion and diffusion kurtosis imaging that involve more
      sophisticated approaches to diffusion quantification.

PMID- 29176468
TI  - Fat Quantification in the Abdomen.
AB  - Fatty liver disease is characterized histologically by hepatic steatosis, the
      abnormal accumulation of lipid in hepatocytes. It is classified into alcoholic
      fatty liver disease and nonalcoholic fatty liver disease, and is an increasingly
      important cause of chronic liver disease and cirrhosis. Assessing the severity of
      hepatic steatosis in these conditions is important for diagnostic and prognostic
      purposes, as hepatic steatosis is potentially reversible if diagnosed early. The
      criterion standard for assessing hepatic steatosis is liver biopsy, which is
      limited by sampling error, its invasive nature, and associated morbidity. As
      such, noninvasive imaging-based methods of assessing hepatic steatosis are
      needed. Ultrasound and computed tomography are able to suggest the presence of
      hepatic steatosis based on imaging features, but are unable to accurately
      quantify hepatic fat content. Since Dixon's seminal work in 1984, magnetic
      resonance imaging has been used to compute the signal fat fraction from chemical
      shift-encoded imaging, commonly implemented as out-of-phase and in-phase imaging.
      However, signal fat fraction is confounded by several factors that limit its
      accuracy and reproducibility. Recently, advanced chemical shift-encoded magnetic
      resonance imaging methods have been developed that address these confounders and
      are able to measure the proton density fat fraction, a standardized, accurate,
      and reproducible biomarker of fat content. The use of these methods in the liver,
      as well as in other abdominal organs such as the pancreas, adrenal glands, and
      adipose tissue will be discussed in this review.

PMID- 29176470
TI  - Quantitative Methods in Abdominal MRI: Perfusion Imaging.
AB  - Recent improvements in arterial spin labeled (ASL) and vastly undersampled
      dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) acquisitions are
      providing a new opportunity to explore the routine use of quantitative perfusion
      imaging for evaluation of a variety of abdominal diseases in clinical practice.
      In this review, we discuss different approaches for the acquisition and data
      analysis of ASL and DCE MRI techniques for quantification of tissue perfusion and
      present various clinical applications of these techniques in both neoplastic and
      non-neoplastic conditions in the abdomen.

PMID- 29176471
TI  - Association of Annular Defect Width After Lumbar Discectomy With Risk of Symptom
      Recurrence and Reoperation: Systematic Review and Meta-analysis of Comparative
      Studies.
AB  - STUDY DESIGN: Systematic review and meta-analysis of comparative studies.
      OBJECTIVE: To characterize the association of annular defect width after lumbar
      discectomy with the risk of symptom recurrence and reoperation. SUMMARY OF
      BACKGROUND DATA: Large annular defect width after lumbar discectomy has been
      reported to increase risk of symptom recurrence. However, this association has
      not been evaluated in a systematic manner. METHODS: A systematic literature
      search of MEDLINE and EMBASE was performed to identify comparative studies of
      large versus small annular defects following lumbar discectomy that reported
      symptom recurrence or reoperation rates. Main outcomes were reported with pooled
      odds ratios (OR) and 95% confidence intervals (CIs). Sensitivity analyses were
      performed to assess the robustness of the meta-analysis findings. RESULTS: After
      screening 696 records, we included data from 7 comparative studies involving 1653
      lumbar discectomy patients, of whom 499 (30%) had large annular defects and 1154
      (70%) had small annular defects. Methodological quality of studies was good
      overall. The median follow-up period was 2.9 years. The risk of symptom
      recurrence (OR = 2.5, 95% CI = 1.3-4.5, P = 0.004) and reoperation (OR = 2.3, 95%
      CI = 1.5-3.7, P < 0.001) was higher in patients with large versus small annular
      defects. Publication bias was not evident. The associations between annular
      defect width and risk of symptom recurrence and reoperation remained
      statistically significant in all sensitivity analyses. CONCLUSION: Annular defect
      width after lumbar discectomy is an under-reported modifier of patient outcome.
      Risk for symptom recurrence and reoperation is higher in patients with large
      versus small annular defects following lumbar discectomy. LEVEL OF EVIDENCE: 2.

PMID- 29176473
TI  - Shifting Practice in the Diagnosis of Paediatric Coeliac Disease in English
      District General Hospitals.

PMID- 29176472
TI  - Omes of Inflammatory Bowel Disease: A Primer for Clinicians.
AB  - Recent advances in high-throughput laboratory technologies and bioinformatics
      tools are redefining how we view inflammatory bowel disease (IBD). Instead of 2
      diseases, we now see a diverse set of molecular subtypes. Large-scale
      investigation of the genome, exome, transcriptome, proteome, metabolome,
      microbiome, and epigenome are providing transformative insights into the
      pathophysiology of IBD, with the promise of accurately predicting prognosis and
      targeting therapy. Understanding these tools and their application is crucial to
      navigating the molecular era of IBD. This review aims to help the IBD clinician
      understand, appreciate, and eventually incorporate this coming paradigm shift to
      improve the care of children with IBD.

PMID- 29176474
TI  - Hepatic Parenchymal Injury in Crigler-Najjar Type I.
AB  - BACKGROUND: Crigler-Najjar syndrome type I (CNI) arises from biallelic variants
      of UGT1A1 that abrogate uridine diphosphate glucuronosyltransferase (UGT1A1)
      activity resulting in unconjugated hyperbilirubinemia. Historically, liver
      parenchyma in CNI was considered structurally and histologically normal. Recent
      review of CNI liver explants revealed fibrosis. Our aim was to investigate the
      association between hepatic histology and disease phenotype in CNI. METHODS: We
      extracted data from the medical record at the time of liver transplant from 22
      patients with CNI at the Children's Hospital of Pittsburgh, and reviewed explant
      histology. Continuous data were normally distributed, are presented as mean (+/-1
      SD), and analyzed using two-tailed Student t-test. Categorical data were analyzed
      using the Chi-square test. RESULTS: Both alanine transaminase (ALT; mean 87.4
      IU/L) and aspartate transaminase (AST; mean 54.6 IU/L) were elevated. Nine (41%)
      of 22 explants had significant fibrosis. Pericentral (n = 5), periportal (n = 2),
      and mixed (n = 2) patterns of fibrosis occurred. A significant difference in mean
      age of subjects with fibrotic versus non-fibrotic livers (16.1 years vs 10.5
      years; P = 0.02) was seen. There were no indices of synthetic liver dysfunction
      or portal hypertension. Neither a history of gallstone disease nor excess weight
      appeared to contribute to the development of fibrosis. CONCLUSIONS: For the first
      time, we report a 41% prevalence of clinically silent, yet histologically
      significant fibrosis among subjects with Crigler-Najjar type 1. Risk for fibrosis
      appears to accrue with time, indicating that earlier intervention may be prudent
      whenever considering alternative treatments such as hepatocyte transplant,
      auxiliary liver transplant, or viral gene therapy.

PMID- 29176475
TI  - Pneumatosis Cystoides Intestinalis.

PMID- 29176476
TI  - Safety and Efficacy of Reslizumab for Children and Adolescents With Eosinophilic
      Esophagitis Treated for 9 Years.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic disease characterized by
      infiltration of eosinophils in the esophageal epithelium. There are limited
      treatment options for EoE. The rationale of the study was to evaluate the long
      term safety and efficacy of reslizumab (RSZ) in pediatric patients who received
      RSZ in a randomized controlled trial (RCT) and expanded access program. METHODS:
      Records of patients who received RSZ in our center were reviewed. Patients
      received RSZ 2 mg/kg (or placebo) every 4 weeks as part of the RCT, open-label
      extension (OLE), and compassionate use (CU). Data were analyzed as of their most
      recent evaluation in August 2017. Labwork, history, and examinations were
      conducted every 12 weeks. Biopsy results were compared from baseline (before RCT)
      and at the most recent evaluation. Adverse events (AE) were recorded. RESULTS:
      Twelve patients entered the RCT at our center; 6 patients completed the OLE and 4
      received RSZ through CU. Between the RCT, OLE, and CU periods, patients received
      549 doses of RSZ (median 37, range 2-116). No serious AE were attributed to RSZ.
      Symptoms improved on treatment: dysphagia (42% vs 0%), abdominal pain (58% vs
      0%), heartburn (18% vs 0%), vomiting (67% vs. 17%), reflux (58% vs. 0%). Median
      esophageal eosinophil count improved (35 eosinophils per high-power field vs 3, P
      < 0.001). Patients receiving RSZ maintain a relatively unrestricted diet.
      CONCLUSIONS: RSZ appears to be safe in children with EoE over 9 years of
      treatment experience. Symptoms and eosinophil count improved considerably during
      treatment with RSZ despite a relatively unrestricted diet.

PMID- 29176477
TI  - Noninvasive Methods of Predicting Large Esophageal Varices in Children With
      Intrahepatic Portal Hypertension.
AB  - OBJECTIVE: Esophageal variceal bleeding is a severe complication of portal
      hypertension. The standard diagnostic screening test and therapeutic procedure
      for esophageal varices (EV) is endoscopy, which is invasive in pediatric
      patients. This study aimed to evaluate the role of noninvasive parameters as
      predictors of large varices in children with intrahepatic portal hypertension.
      METHODS: Participants included in this cross-sectional study underwent a
      screening endoscopy. Variceal size, red marks, and portal gastropathy were
      assessed and rated. Patients were classified into two groups: Group 1 (G1) with
      small or no varices and Group 2 (G2) with large varices. The population consisted
      of 98 children with no history of gastrointestinal (GI) bleeding, with a mean age
      of 8.9 +/- 4.7 years. The main outcome evaluated was the presence of large
      varices. RESULTS: The first endoscopy session revealed the presence of large
      varices in 32 children. The best noninvasive predictors for large varices were
      platelets (Area under the ROC Curve [AUROC] 0.67; 95% CI 0.57-0.78), the Clinical
      Prediction Rule (CPR; AUROC 0.65; 95% CI 0.54-0.76), and risk score (AUROC 0.66;
      95% CI 0.56-0.76). The logistic regression model showed that children with a CPR
      value under 114 were 8.59 times more likely to have large varices. Risk scores
      higher than -1.2 also increased the likelihood of large varices (OR 6.09; P =
      0.014), as did a platelet count/spleen size z score lower than 25 (OR 3.99; P =
      0.043). The combination of these three tests showed a high negative predictive
      value. CONCLUSIONS: The CPR, the risk score, and the platelet count/spleen size z
      score could be helpful in identifying cirrhotic children who may be eligible for
      endoscopy.

PMID- 29176478
TI  - Vitamin B1 Deficiency Related to Excessive Soft Drink Consumption in Japan.
AB  - The aim of this study was to clarify the picture of vitamin B1 deficiency (VB1D)
      caused by excessive soft drink consumption in Japan. A nationwide survey of
      children with soft drink-induced VB1D was conducted using a structured research
      form. Patient information was obtained from 2 sources: training hospitals for
      board-certified pediatricians and those identified by a database search. We
      obtained data from 33 children. Twenty-one children had a nonnurturing home
      environment. The median duration of excessive soft drink intake was 3.5 months
      and the daily intake was 1000 mL or more in 25 children. Infection was the most
      common reason for excessive soft drink consumption. Only 4 children had the
      classical triad of Wernicke encephalopathy. One child died, and 12 had
      neurological sequelae. A majority of children with soft drink-induced VB1D did
      not have a nurturing home environment. It is imperative to establish measures to
      prevent future cases of VB1D.

PMID- 29176479
TI  - Effect of Long-Term Diving on the Morphology and Growth of the Distal Radial
      Epiphyseal Plate of Young Divers: A Magnetic Resonance Imaging Study.
AB  - OBJECTIVE: To investigate the effects of long-term diving on the morphology and
      growth of the distal radial epiphyseal plate in young divers. STUDY DESIGN:
      Cohort study. SETTING: Guangzhou Sport University. PARTICIPANTS: Thirty-eight
      professional divers, aged 10 to 17 years, and 25 age-matched volunteers.
      INTERVENTIONS: Each subject received a physical examination at the beginning of
      the study and underwent bilateral magnetic resonance imaging of the wrist. The
      divers were divided into 2 groups depending on the status of the epiphyseal
      plate: group A (positive distal radial epiphyseal plate injury) and group B (no
      positive distal radial epiphyseal plate injury). A third group, group C,
      consisted of the 25 volunteers. MAIN OUTCOME MEASURES: The frequency of distal
      radial epiphyseal plate injury and the thickness of the distal radial epiphyseal
      plate were analyzed across the 3 groups. RESULTS: Twenty-nine cases (29/76,
      38.15%) of distal radial epiphyseal plate injury were observed in 20 divers
      (20/38, 52.63%). The incidence of injury to the right hand was higher than that
      for the left (P = 0.009). There were statistically significant differences (P =
      0.000) among the 3 groups in terms of epiphyseal plate thickness; group A > group
      B > group C. CONCLUSIONS: Distal radial epiphyseal plate injury is common in
      divers, and more injuries are seen in the right hand. Moreover, growth of the
      radius was impaired in divers relative to controls. We consider that loading
      during diving may influence growth of the epiphyseal plate in either a transient
      or permanent manner.

PMID- 29176480
TI  - How does sinus surgery affect topical irrigation distribution?
AB  - PURPOSE OF REVIEW: The current article reviews the literature on the distribution
      of nasal irrigation in the treatment of chronic sinusitis, especially in how
      sinus surgery and irrigation techniques affect its delivery to the nasal cavity
      and paranasal sinuses. RECENT FINDINGS: Nasal irrigation has become a useful tool
      in the treatment of chronic sinusitis. Used after endoscopic surgery of the
      paranasal sinuses, irrigation has shown to be effective in improving edema and
      removing crusts and secretions in that place. However, some relevant points have
      been considered in the surgical technique and in the postoperative period to
      improve irrigation access to the paranasal sinuses such as the amplitude of the
      sinus ostial opening, irrigation volume and device used, as well as head position
      during irrigation. SUMMARY: Postoperative lavage of the paranasal sinus is a
      recognized adjuvant in the treatment of chronic rhinosinusitis, reducing
      morbidity and improving local healing, besides allowing the association of
      topical medications that can be carried to the paranasal sinuses along with the
      saline increasing the reach of these drugs. Detailed attention to the techniques
      described in this review improves the distribution of irrigation in the paranasal
      sinuses after sinus surgery and considerably increases the efficacy of this
      therapy.

PMID- 29176481
TI  - The asthma-obesity relationship: underlying mechanisms and treatment
      implications.
AB  - PURPOSE OF REVIEW: Obesity is a worldwide epidemic with a prevalence that has
      tripled in the last two decades. Worldwide, more than 1.5 billion adults are
      overweight and more than 500 million obese. Obesity has been suggested to be a
      risk factor for the development of more difficult-to-control asthma. Although the
      mechanisms underlying the asthma-obesity relationship are not fully understood,
      several possible explanations have been put forward. These will be reviewed in
      this manuscript as well as the implications for the treatment of overweight and
      obese asthma patients. RECENT FINDINGS: Insulin resistance is a possible factor
      contributing to the asthma-obesity relationship and the effect is independent of
      other components of the metabolic syndrome such as hypertriglyceridemia,
      hypertension, hyperglycemia, and systemic inflammation. Obesity has important
      effects on airway geometry, by especially reducing expiratory reserve volume
      causing obese asthmatics to breathe at low lung volumes. Furthermore, obesity
      affects the type of inflammation in asthma and is associated with reduced inhaled
      corticosteroids treatment responsiveness. SUMMARY: Obesity induces the
      development of asthma with a difficult-to-control phenotype. Treatment targeting
      insulin resistance may be beneficial in obese asthma patients, especially when
      they have concomitant diabetes. Systemic corticosteroids should be avoided as
      much as possible as they are not very effective in obese asthma and associated
      with side-effects like diabetes, weight gain, and osteoporosis.

PMID- 29176482
TI  - Widespread Erythematous and Bullous Plaques Associated With Nasolabial Fold
      Ulceration.

PMID- 29176484
TI  - Process for Consensus Statements on Lumbar Total Disc Replacement.
AB  - : Consensus statements regarding the evidence-base for lumbar total disc
      replacement, as it pertains to payer decision-making, were developed through a
      modified-Delphi technique involving 17 spine surgeons and a former payer medical
      director. The Delphi process involved one round of anonymous survey and one round
      with a face-to-face meeting. The survey was a 51-item, electronically
      administered questionnaire to determine level of agreement with proposed
      statements on the evidence for lumbar total disc replacement and to provide
      additional diagnosis and management practice information for further
      deliberations. A subset of the proposed statements was discussed at the face-to
      face meeting to identify reasons for disagreement, revise wording, and obtain
      consensus. The meeting involved presentation of the current evidence base for
      lumbar total disc replacement, as well as three themed sessions that were
      moderated by surgeons on the panel. The voting processes during meeting
      deliberations remained anonymous. Consensus was defined as >= 90% agreement.
      Consensus was reached on 11 statements, divided into themes that focused on
      patient eligibility and diagnosis, evidence criteria for coverage decisions,
      clinical evidence, and budgetary implications.

PMID- 29176483
TI  - Foreword: Proceedings From the First Annual Lumbar Total Disc Replacement Summit.
AB  - : This publication focuses on proceedings from the First Annual Lumbar Total Disc
      Replacement Summit, held October 25, 2016 in Boston, MA. The Summit brought
      together 17 thought leading surgeons who employed a modified-Delphi method to
      determine where consensus existed pertaining to the utilization of lumbar total
      disc replacement as a standard of care for a subpopulation of patients suffering
      from degenerative disc disease.

PMID- 29176485
TI  - Defining the Ideal Lumbar Total Disc Replacement Patient and Standard of Care.
AB  - : Lumbar total disc replacement, now in use since 2004, was determined by the
      panel to be a standard of care for the treatment of symptomatic single-level
      lumbar degenerative disc disease in the active patient subpopulation as outlined
      by the investigational device exemption study criteria. The large body of
      evidence supporting this statement, including surgeons' experiences, was
      presented and discussed. Consensus statements focusing on decision-making
      criteria reflected that efficacy, long-term safety, clinical outcomes with
      validated measures, and cost-effectiveness should form the basis of decision
      making by payers. Diagnostic challenges with lumbar degenerative disc disease
      patients were discussed among the panel, and it was concluded that although
      variably used among surgeons, reliable tools exist to appropriately diagnose
      discogenic back pain.

PMID- 29176486
TI  - Challenges and Solutions for Lumbar Total Disc Replacement Implantation.
AB  - : Long-term data are now available to support the safety and efficacy of lumbar
      total disc replacement (TDR). Five-year randomized and controlled trials, meta
      analyses, and observational studies support a similar or lower risk of
      complications with lumbar TDR compared with fusion. The panel concluded that
      published data on commercially available lumbar TDR devices demonstrate minimal
      concerns with late-onset complications, and that the risk of adjacent segment
      degeneration and reoperations can be reduced with lumbar TDR versus fusion.
      Survey results of surgeon practice experiences supported the evidence, revealing
      a low rate of complications with TDR. Panelists acknowledged the importance of
      adhering to selection criteria to help minimize patient complications.

PMID- 29176487
TI  - Barriers to and Budget Impact of Lumbar Total Disc Replacement Utilization.
AB  - : Evidence on the favorable efficacy, safety, and cost effectiveness of lumbar
      total disc replacement (TDR) compared with fusion for lumbar degenerative disc
      disease is mounting; however, a key barrier identified for TDR utilization is
      lack of coverage by US health insurers. Although economic considerations in a fee
      for-service model should not be a determining factor in patient access, concerns
      regarding the budget impact of lumbar TDR surgery may unfortunately underlie
      coverage decisions. On the basis of the data available and economic modeling, the
      panel agreed that there is no indication that there would be a dramatic increase
      in patients seeking lumbar TDR. Considering several possible scenarios on
      potential growth in TDR utilization with coverage, as well as growth in the
      overall surgical pool of patients, economic modeling demonstrated that adoption
      of lumbar TDR would result in minimal or no budget impact for commercial
      insurance plans. Considering these model results and the economic literature, the
      panel concluded that adopting lumbar TDR within a coverage policy is expected to
      remain cost neutral for the insurer.

PMID- 29176488
TI  - Greeting From the Chairman: Evolution or Revolution? Our Time has Come!

PMID- 29176489
TI  - Treatment of Axis Body Fractures: A Systematic Review.
AB  - STUDY DESIGN: Evidence-based systematic review. OBJECTIVES: To define the optimal
      treatment of fractures involving the C2 body, including those with concomitant
      injuries, based upon a systematic review of the literature. SUMMARY OF BACKGROUND
      DATA: Axis body fractures have customarily been treated nonoperatively, but there
      are some injuries that may require operative intervention. High-quality
      literature is sparse and there are few class I or class II studies to guide
      treatment decisions. MATERIALS AND METHODS: A literature search was conducted
      using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and
      Scopus (EMBASE, MEDLINE, COMPENDEX). The quality of literature was rated
      according to a grading tool developed by the Center for Evidence-based Medicine.
      Operative and nonoperative treatment of axis body fractures were compared using
      fracture bony union as the primary outcome measure. As risk factors for nonunion
      were not consistently reported, cases were analyzed individually. RESULTS: The
      literature search identified 62 studies, of which 10 were case reports which were
      excluded from the analysis. A total of 920 patients from 52 studies were
      included. The overall bony union rate for all axis body fractures was 91%.
      Although the majority of fractures were treated nonoperatively, there has been an
      increasing trend toward operative intervention for Benzel type III (transverse)
      axis body fractures. Nearly 76% of axis body fractures were classified as type
      III fractures, of which 88% united successfully. Nearly all Benzel type I and
      type II axis body fractures were successfully treated nonoperatively. The risk
      factors for nonunion included: a higher degree of subluxation, fracture
      displacement, comminution, concurrent injuries, delay in treatment, and older
      age. CONCLUSIONS: High rates for fracture union are reported in the literature
      for axis body fractures with nonoperative treatment. High-quality prospective
      studies are required to develop consensus as to which C2 body fractures require
      operative fixation.

PMID- 29176490
TI  - Incidental Durotomy in Open Versus Tubular Revision Microdiscectomy: A
      Retrospective Controlled Study on Incidence, Management, and Outcome.
AB  - STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To compare the
      incidence, management, and outcome of incidental durotomy in revision
      microdiscectomy with open and minimal-access surgery. SUMMARY OF BACKGROUND DATA:
      Incidental durotomy occurs with a variable incidence of 3%-27% in spine surgery.
      The highest rate occurs in revision microdiscectomy. The intraoperative and
      postoperative management of dural tears varies in the literature and the definite
      impact on clinical outcome has to be clarified. METHODS: This is a retrospective
      study of medical records of 135 patients who underwent revision microdiscectomy,
      divided into 2 subgroups: OPEN (n=82) versus minimal-access surgery (MINI, n=53).
      Occurrence of intraoperative dural tears, intraoperative and postoperative
      management of durotomy, and clinical outcomes, according to MacNab criteria, were
      retrospectively examined. Statistical comparisons for categorical values between
      groups were accomplished using the 2-tailed Fisher exact test. P-values <0.05
      were considered to be statistically significant. RESULTS: The incidence of
      durotomy in group OPEN was 19.5% (n=16/82) and in group MINI 17.0% (n=9/53)
      (P=0.822). The majority of durotomies (23/25) were repaired with an absorbable
      fibrin sealant patch alone. Postoperative cerebrospinal fluid fistula occurred
      only in 1 case of the OPEN group and was treated with lumbar drainage without the
      need for a reoperation. Patients with durotomy of the MINI group tended to have
      better outcome compared with those of the OPEN group without being statistically
      significant. CONCLUSIONS: The incidence of durotomy and postoperative
      cerebrospinal fluid fistula in lumbar revision microdiscectomy does not
      significantly differ between minimal-access and standard open procedures. The
      application of a fibrin sealant patch alone is an effective strategy for dural
      repair in revision lumbar microdiscectomy.

PMID- 29176491
TI  - Impact of Anemia and Transfusion on Readmission and Length of Stay After Spinal
      Surgery: A Single-center Study of 1187 Operations.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine whether receipt
      of blood transfusion and preoperative anemia are associated with increased rates
      of 30-day all-cause readmission, and secondarily with a prolonged hospital stay
      after spinal surgery. SUMMARY OF BACKGROUND DATA: Increased focus on health care
      quality has led to efforts to determine postsurgical readmission rates and
      predictors of length of postoperative hospital stay. Although there are still no
      defined outcome measures specific to spinal surgery to which providers are held
      accountable, efforts to identify appropriate measures and to determine modifiable
      risk factors to optimize quality are ongoing. METHODS: Records from 1187
      consecutive spinal surgeries at Northwestern Memorial Hospital in 2010 were
      retrospectively reviewed and data were collected that described the patient,
      surgical procedure, hospital course, complications, and readmissions. Presence or
      absence of transfusion during the surgery and associated hospital course was
      treated as a binary variable. Multivariate negative binomial regression and
      logistic regression were used to model length of stay and readmission,
      respectively. RESULTS: Nearly one fifth (17.8%) of surgeries received
      transfusions, and the overall readmission rate was 6.1%. After controlling for
      potential confounders, we found that the presence of a transfusion was associated
      with a 60% longer hospital stay [adjusted incidence rate ratio=1.60 (1.34-1.91),
      P<0.001], but was not significantly associated with an increased rate of
      readmission [adjusted odds ratio=0.81 (0.39-1.70), P=0.582]. Any degree of
      preoperative anemia was associated with increased length of stay, but only severe
      anemia was associated with an increased rate of readmission. CONCLUSIONS: Both
      receipt of blood transfusion and any degree of preoperative anemia were
      associated with increased length of hospital stay after controlling for other
      variables. Severe anemia, but not receipt of blood transfusion, was associated
      with increased rate of readmission. Our findings may help define actions to
      reduce length of stay and decrease rates of readmission.

PMID- 29176492
TI  - The Weight-Bearing Shoulder.
AB  - The shoulder achieves a wide spectrum of motion, and in a subset of patients,
      including those who use manual wheelchairs and upper extremity walking aids, the
      shoulder also serves as the primary weight-bearing joint. Because the weight
      bearing shoulder is subject to considerable joint reaction forces and overuse, a
      broad spectrum of pathology can affect the joint. The combination of muscle
      imbalance and repetitive trauma presents most commonly as subacromial impingement
      syndrome but can progress to other pathology. Patients with high-level spinal
      cord injury, leading to quadriplegia and motor deficits, have an increased
      incidence of shoulder pain. Understanding the needs of patients who use manual
      wheelchairs or walking aids can help the physician to better comprehend the
      pathology of and better manage the weight-bearing shoulder.

PMID- 29176493
TI  - The Relative Effects of Manual Versus Automatic Exposure Control on Radiation
      Dose to Vital Organs in Total Hip Arthroplasty.
AB  - INTRODUCTION: Technologic advances have reduced medical radiation exposure while
      maintaining image quality. The purpose of this study was to determine the effects
      of the presence of total hip arthroplasty implants, compared with native hips, on
      radiation exposure of the most radiosensitive organs when manual and automatic
      exposure control settings are used. METHODS: Detection probes were placed at six
      locations (stomach, sigmoid colon, right pelvic wall, left pelvic wall, pubic
      symphysis, and anterior pubic skin) in a cadaver. Radiographs were obtained with
      the use of manual and automatic exposure control protocols, with exposures
      recorded. A total hip arthroplasty implant was placed in the cadaver, probe
      positioning was confirmed, and the radiographs were repeated, with exposure
      values recorded. RESULTS: The control probe placed at the stomach had values
      ranging from 0.00 mSv to 0.01 mSv in protocols with and without implants. With
      the manual protocol, exposures in the pelvis ranged from 0.36 mSv to 2.74 mSv in
      the native hip and from 0.33 mSv to 2.24 mSv after implant placement. The
      increases in exposure after implant placement, represented as relative risk, were
      as follows: stomach, 1.000; pubic symphysis, 0.818; left pelvic wall, 1.381;
      sigmoid colon, 1.550; right pelvic wall, 0.917; and anterior pubic skin, 1.015.
      With automatic exposure control, exposures in the pelvis ranged from 0.07 mSv to
      0.89 mSv in the native hip and from 0.21 mSv to 1.15 mSv after implant placement.
      With automatic exposure control, the increases in exposure after implant
      placement, represented as relative risk, were as follows: stomach, 1.000; pubic
      symphysis, 1.292; left pelvic wall, 1.476; sigmoid colon, 2.182; right pelvic
      wall, 3.000; and anterior pubic skin, 1.378. DISCUSSION: The amount of radiation
      to which patients are exposed as a result of medical procedures or imaging, and
      whether exposure is associated with an increased risk of malignant
      transformation, are the subject of ongoing debate. We found that after insertion
      of a total hip arthroplasty implant, exposure values increased threefold at some
      anatomic locations and surpassed 1 mSv, the generally accepted threshold for
      concern. CONCLUSION: Radiation exposure to radiosensitive organs increased up to
      threefold after total hip implantation with automatic exposure control and up to
      approximately 1.5 times with the manual protocol. Doses were greater with manual
      exposures than with automatic exposure control (except at the control probe on
      the stomach, where exposure was negligible, as expected). However, after implant
      placement, doses increased more with automatic exposure control than with manual
      exposure. This difference can be attributed to increased scatter and the
      difficulty of dose modification because of the density of the implant. Current
      radiographic protocols should be reassessed to determine if the benefits of
      frequent radiographs outweigh the newly demonstrated risks.

PMID- 29176495
TI  - Soft Factors, Smooth Transport? The role of safety climate and team processes in
      reducing adverse events during intrahospital transport in intensive care.
AB  - BACKGROUND: Intrahospital patient transports (IHTs) in intensive care involve an
      appreciable risk of adverse events (AEs). Research on determinants of AE
      occurrence during IHT has hitherto focused on patient, transport, and intensive
      care unit (ICU) characteristics. By contrast, the role of "soft" factors,
      although arguably relevant for IHTs and a topic of interest in general health
      care settings, has not yet been explored. PURPOSE: The study aims at examining
      the effect of safety climate and team processes on the occurrence of AE during
      IHT and whether team processes mediate the effect of safety climate.
      METHODOLOGY/APPROACH: Data stem from a noninterventional, observational
      multicenter study in 33 ICUs (from 12 European countries), with 858 transports
      overall recorded during 28 days. AEs include medication errors, dislodgments,
      equipment failures, and delays. Safety climate scales were taken from the
      "Patient Safety Climate in Healthcare Organizations" (short version), team
      processes scales from the "Leiden Operating Theatre and Intensive Care Safety"
      questionnaire. Patient condition was assessed with NEMS (Nine Equivalents of
      Nursing Manpower Use Score). All other variables could be directly observed.
      Hypothesis testing and assessment of effects rely on bivariate correlations and
      binomial logistic multilevel models (with ICU as random effect). FINDINGS: Both
      safety climate and team processes are comparatively important determinants of AE
      occurrence, also when controlling for transport-, staff-, and ICU-related
      variables. Team processes partially mediate the effect of safety climate. Patient
      condition and transport duration are consistently related with AE occurrence,
      too. PRACTICE IMPLICATIONS: Unlike most patient, transport, and ICU
      characteristics, safety climate and team processes are basically amenable to
      managerial interventions. Coupled with their considerable effect on AE
      occurrence, this makes pertinent endeavors a potentially promising approach for
      improving patient safety during IHT. Although literature suggests that safety
      climate is slow and hard to change (also compared to team processes), efforts to
      improve safety climate should not be forgone.

PMID- 29176494
TI  - Pancreatic Enzyme Replacement Therapy Use in Infants With Cystic Fibrosis
      Diagnosed by Newborn Screening.
AB  - OBJECTIVES: The aim of the study is to describe pancreatic enzyme practices
      during the first year of life in infants with cystic fibrosis (CF) and evaluate
      associations between dosing and outcomes, including growth and gastrointestinal
      (GI) symptoms. METHODS: We analyzed data from a subset of infants who were in a
      prospective cohort study conducted at 28 US CF centers. Anthropometric
      measurements and medications were recorded at each visit. Diaries with infant
      diet, pancreatic enzyme replacement therapy (PERT) dosing, stool frequency and
      consistency, and pain were completed by a parent/guardian for 3 days before each
      visit. RESULTS: Two hundred and thirty-one infants were enrolled in the main
      study; 205 of these met criteria for pancreatic insufficiency (PI). PERT dose
      between birth and 6 months was on average 1882 LU/kg per meal (range: 492-3727)
      and was similar between 6 and 12 months (mean: 1842 LU/kg per mean, range: 313
      3612). PERT dose had a weak, negative association with weight z score at 3 and 6
      months (r = -0.16, 95% confidence interval [CI] -0.29 to -0.02 and r = -0.18, 95%
      CI -0.31 to -0.04, respectively) but not at 12 months. There was not a clear
      relationship between PERT dosing and number of stools per day, stool consistency
      or pain. One hundred and forty-four infants (70%) were placed on acid suppression
      medication. Weight z score mean was 0.37 higher in infants using proton pump
      inhibitors (PPIs) exclusively versus those using histamine-2 blockers exclusively
      (95% CI -0.02 to 0.76, P = 0.06). CONCLUSIONS: We did not observe that centers
      with a higher PERT dosing strategy yielded greater clinical benefit than dosing
      at the lower end of the recommended range.

PMID- 29176496
TI  - Hospitals' adoption of medical device registers: Evidence from the German
      Arthroplasty Register.
AB  - BACKGROUND: Hospitals in many countries do not record and analyze artificial hip
      and knee joint surgeries systematically, leading to a lack of reliable quality
      assurance data. Arthroplasty registers have the potential to alleviate this and
      improve quality of care and health care expenditures. In Germany, the current
      introduction of the Arthroplasty Register acts as a prototype for various medical
      device registers. However, participation is voluntary for hospitals in most
      countries, leading to problems with nonadoption. PURPOSE: Implementing successful
      registers requires adoption by most relevant hospitals. Therefore, we assess
      variables influencing medical device register adoption. METHODOLOGY: We collect
      longitudinal data from 343 hospitals that are potential adopters of the German
      Arthroplasty Register in two surveys. The first survey on the implementation
      process is conducted in 2014; the second survey is conducted in 2016 to collect
      data on actual adoption of the surveyed hospitals in 2014. The survey data are
      matched with published hospital characteristics and administrative data. The
      hypotheses are tested with a mediated regression model, using partial least
      squares structural equation modeling. FINDINGS: Hospital specialization
      positively affects adoption, directly and indirectly, depending on top management
      support and user involvement. Quality benefits and hospital size impact adoption
      positively; economic benefits impact adoption negatively. CONCLUSION: Important
      factors influencing adoption of medical device registers for the first time were
      revealed in this study, providing a starting point to influence adoption
      proactively and avoid nonadoption. PRACTICE IMPLICATIONS: The results provide
      important guidelines for decision-makers at hospitals, registers, and health
      insurance companies and policy makers about how to foster register adoption and
      encourage hospitals toward adopting medical device registers.

PMID- 29176497
TI  - Agreement Among Clinician, Patient, and Independent Interviewer Ratings of
      Adaptive Functioning.
AB  - We examined the interrater reliability and diagnostic efficiency of clinician
      report (both the treating clinician and independent expert clinical interviewer)
      and patient self-report of clinically meaningful information pertaining to
      adaptive functioning. A convenience sample of clinicians (N = 80) and patients (N
      = 170) from eight community mental health clinics in Israel participated in the
      study. Our findings suggest that clinicians overall reliably report on adaptive
      functioning of patients (overall correct classification rates range, 0.74-0.98).
      Yet, in some areas, they may fail to collect necessary information such as self
      mutilation history, loss of job in the past 5 years, and adult physical abuse.
      The patterns of higher versus lower diagnostic efficiency suggest that both
      treating clinicians and independent clinician interviewers tend to make judgments
      conservatively, essentially sacrificing sensitivity for specificity, not
      diagnosing events unless they were certain, thus maximizing false-negatives and
      minimizing false-positives.

PMID- 29176500
TI  - A Pilot Study of a Topical Intervention for Treatment of Female Sexual
      Dysfunction.
AB  - PURPOSE/BACKGROUND: Many investigators reported that pharmacological treatment of
      female sexual dysfunction (FSD) has been a promising field yet to be explored.
      The purpose of this pilot study was to investigate the efficacy and safety of a
      topical cream containing small concentrations of three vasodilators with
      different mechanisms of action in treating FSD. METHODS: In this randomized,
      controlled pilot trial, premenopausal (n = 30) and postmenopausal (n = 30) cases
      of 21- to 62-year age range with FSD were allocated randomly into 15 given
      placebo or 15 given active cream in each group. The women included had FSD for
      more than a 6-month duration and a total score of Female Sexual Distress Scale
      Revised of at least 15. Assessing sexual function by measuring female sexual
      function index (FSFI) during five clinic visits, one at the end of baseline week
      and at the end of each week of the 4-week treatment period. The primary end point
      was changed from baseline FSFI total scores to week 4 treatment. Secondary end
      point included the changes from baseline arousal, desire, orgasm, and
      satisfaction scores to week 4 treatment. FINDINGS/RESULTS: The sexual problem
      reported by patients was orgasmic or/and arousal disorders. In premenopausal
      cases, active cream led to a high significant increase in mean change FSFI total
      score from the baseline to week 4 compared with placebo (1.7 +/- 1.886 vs 13.35
      +/- 4.646, respectively; P < 0.0001). Greater improvement of mean change of
      orgasm and arousal domain score was also observed (0.3 +/- 0.45 and 0.35 +/- 0.39
      vs. 2.66 +/- 0.63 and 1.87 +/- 0.168, respectively; P < 0.0001). In
      postmenopausal cases, there were significantly greater improvements with active
      cream in all sexual functions compared with placebo cream (P < 0.0001). In triple
      cream, mean change of FSFI total score, orgasm domain score, and arousal score
      domain were 14.85 +/- 6.33, 1.87 +/- 0.168 and 2.66 +/- 1.182, whereas in the
      placebo cream, they were 1.54 +/- 2.1,0.7 +/- 0.76 and 0.22 +/- 0.44,
      respectively. Meanwhile, orgasm scores increased significantly after the use of
      placebo cream. No serious adverse effects were reported during treatment.
      IMPLICATIONS/CONCLUSIONS: The results of the pilot trial suggest that topical
      cream containing small concentrations of three vasodilators may act
      synergistically, and was effective in improving arousal, orgasmic, and
      satisfaction disorder with a safer profile for premenopausal and postmenopausal
      women with FSD. Further studies are recommended to be conducted using a large
      number of nondepressive and depressive patients.

PMID- 29176501
TI  - Phase IIIb safety results from an expanded-access protocol of talimogene
      laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma.
AB  - Talimogene laherparepvec is a genetically modified herpes simplex virus-1-based
      oncolytic immunotherapy for the local treatment of unresectable cutaneous,
      subcutaneous, and nodal tumors in patients with melanoma recurrence following
      surgery. We aim to describe the safety of talimogene laherparepvec. Intralesional
      talimogene laherparepvec was administered at less than or equal to 4 ml*10 PFU/ml
      at protocol day 1, then less than or equal to 4 ml*10 PFU/ml 21 days later, and
      then every 14 days. Treatment continued until complete response, absence of
      injectable tumors, progressive disease, intolerance, or US Food and Drug
      Administration approval. Adverse events were graded during and 30 days after the
      end of treatment. Lesions suspected to have herpetic origin were tested for
      talimogene laherparepvec DNA by quantitative PCR (qPCR). Between September 2014
      and October 2015, 41 patients were enrolled with stage IIIB (22%), IIIC (37%),
      IVM1a (34%), IVM1b (5%), and IVM1c (2%) melanoma. The median age was 72 (range:
      32-96) years and 54% of the patients were men. Patients had an ECOG performance
      status of 0 (68%) or 1 (32%). The median treatment duration was 13.1 (3.0-41.1)
      weeks. Treatment-related adverse events of greater than or equal to grade 3 were
      reported in three (7.3%) patients and included vomiting, upper abdominal pain,
      chills, hyperhidrosis, nausea, pyrexia, and wound infection. Suspected herpetic
      lesions were swabbed in five (12%) patients. One of the five tested positive for
      talimogene laherparepvec DNA by qPCR, but this lesion had been injected
      previously with talimogene laherparepvec. During the study, five patients
      completed treatment because of complete response per investigators. In the
      clinical practice setting, talimogene laherparepvec has a safety profile
      comparable to that observed in previous clinical trials. Talimogene laherparepvec
      (IMLYGIC) is now approved in the US, European Union, and Australia.

PMID- 29176502
TI  - Venous Thromboembolism Prophylaxis in Total Hip Arthroplasty and Total Knee
      Arthroplasty Patients: From Guidelines to Practice.
AB  - Venous thromboembolism (VTE) prophylaxis is recommended for all patients
      undergoing total hip arthroplasty or total knee arthroplasty. The selection of an
      appropriate prophylaxis regimen represents a balance between efficacy and safety.
      To help orthopaedic surgeons select an appropriate VTE prophylaxis regimen for
      their patients, the American Academy of Orthopaedic Surgeons and the American
      College of Chest Physicians have developed guidelines. These guidelines do not
      recommend an optimal regimen, however. Rather, an individualized prophylaxis
      regimen that balances efficacy and safety is recommended for each patient, based
      on various risk factors. Because of a paucity of data and a lack of adequately
      powered head-to-head trials, implementing these guidelines can be challenging for
      the orthopaedic surgeon. Knowledge of the prophylaxis options and the VTE risk
      factors is paramount for developing an effective VTE prophylaxis algorithm for
      the surgeon's practice.

PMID- 29176498
TI  - Zika clinical updates: implications for pediatrics.
AB  - PURPOSE OF REVIEW: Zika virus (ZIKV), a mosquito-borne flavivirus, has gained
      recognition over the past few years as an important new cause of congenital
      infection. As a result, it is critical that pediatricians understand its
      epidemiology, clinical presentation, clinical sequelae, and management. RECENT
      FINDINGS: The recent ZIKV epidemiology, clinical presentation of acute infection
      in children and complications, perinatal infection, and congenital infection will
      be summarized in this ZIKV review. This will be followed by a brief summary on
      ZIKV diagnosis, management, treatment, and prevention. SUMMARY: The field of
      clinical research in ZIKV has rapidly evolved over recent months. It is critical
      that pediatricians continue to stay up-to-date with the continuously evolving
      understanding of the clinical aspects of ZIKV to ensure optimal identification
      and management of affected infants and children. Given the recent changes in
      Centers for Disease Control and Prevention guidelines to limit screening of
      asymptomatic pregnant women in the United States with possible ZIKV exposure,
      comprehensive ZIKV clinical knowledge becomes even more crucial.

PMID- 29176503
TI  - Diagnostic Injections About the Shoulder.
AB  - Injections about the shoulder serve diagnostic as well as therapeutic purposes.
      Diagnosis of shoulder conditions, such as rotator cuff tears, acromioclavicular
      joint pathology, subacromial impingement or anterolateral pain syndrome,
      glenohumeral joint pathology, suprascapular nerve entrapment, and biceps tendon
      pathologies, is often complicated by concomitant conditions with overlapping
      symptoms and by inconclusive physical examination and imaging results. Injections
      of anesthetic agents can often help clinicians locate the source of pain.
      However, technique and accuracy of needle placement can vary by route. Accuracy
      is often improved with the use of ultrasonography guidance, although studies
      differ on the benefits of guided versus unguided injection.

PMID- 29176504
TI  - Screening for Infection Before Revision Hip Arthroplasty: A Meta-analysis of
      Likelihood Ratios of Erythrocyte Sedimentation Rate and Serum C-reactive Protein
      Levels.
AB  - INTRODUCTION: Diagnosing periprosthetic joint infection (PJI) before revision hip
      arthroplasty is critical to ensure effective treatment of patients undergoing
      surgery for reasons other than infection. The main objective of our study is to
      determine whether the erythrocyte sedimentation rate (ESR) and the serum C
      reactive protein (CRP) level are sufficient to use for testing to rule out
      infection in patients undergoing revision hip surgery. METHODS: We performed a
      systematic review of the literature in the MEDLINE, Ovid, and Embase databases.
      We included studies in which the investigators used the ESR (>30 mm/h) and serum
      CRP level (>10 mg/L) for the diagnosis of PJI of the hip. We obtained meta
      estimates of sensitivity, specificity, positive likelihood ratio (LR+), and
      negative likelihood ratio (LR-). RESULTS: From 511 articles, we analyzed 12
      studies in which the investigators reported data on 2,736 patients. Sensitivity
      and specificity for the ESR were 0.860 (95% confidence interval [CI], 0.825 to
      0.890) and 0.723 (95% CI, 0.704 to 0.742), respectively, and for the CRP level
      were 0.869 (95% CI, 0.835 to 0.899) and 0.786 (95% CI, 0.769 to 0.803),
      respectively. For the ESR, LR+ was 3.42 (95% CI, 2.55 to 4.59) and LR- was 0.22
      (95% CI, 0.12 to 0.41). For the CRP level, LR+ was 4.18 (95% CI, 3.42 to 5.11)
      and LR- was 0.20 (95% CI, 0.12 to 0.32). DISCUSSION: With a low pretest
      probability of PJI, a negative test result for either the ESR or CRP level is
      enough to rule out infection before revision hip arthroplasty. LEVEL OF EVIDENCE:
      III.

PMID- 29176505
TI  - Sex-specific Outcomes and Predictors of Concussion Recovery.
AB  - INTRODUCTION: Sports-related concussion (SRC) is a substantial concern in
      collegiate athletics. Some studies of SRC that make comparisons by sex are
      limited by sample size, follow-up duration, or referral bias. Sex-specific
      predictors of occurrence and recovery are uncertain. METHODS: A 15-year
      retrospective cohort study identified 1,200 Columbia University varsity athletes
      (822 male [68.5%], 378 female [31.5%]) at risk of collegiate SRC. RESULTS: A
      total of 228 athletes experienced at least one collegiate concussion, including
      88 female athletes (23.3% of female athletes) and 140 male athletes (17.0% of
      male athletes) (P = 0.01); follow-up data were available on 97.8% of these
      athletes. Postconcussion symptoms were similar by sex, with the exception of
      sleep disturbance (29.3% of male athletes versus 42.0% of female athletes; P =
      0.048) and memory impairment (43.6% of male athletes versus 30.7% of female
      athletes; P = 0.052), although the latter difference was not statistically
      significant. Risk factors for collegiate concussion included female sex (odds
      ratio [OR], 1.5; 95% confidence interval [CI], 1.1 to 2.0) or precollegiate
      concussion (OR, 2.9; 95% CI, 2.2 to 3.9). Prolonged recovery was predicted by the
      presence of eight or more postconcussion symptoms for all athletes (OR, 3.77; 95%
      CI, 1.68 to 8.46) and for female athletes only (OR, 8.24; 95% CI, 1.58 to 43.0);
      this finding was not statistically significant for male athletes. DISCUSSION:
      Female athletes were more likely than male athletes to experience concussion.
      Increasing numbers of prior concussions predicted recurrence. Although most
      postconcussion symptoms were highly intercorrelated, the total number of symptoms
      predicted a prolonged recovery period. CONCLUSION: This study confirms sex-based
      differences in SRCs. Longitudinal studies of collegiate cohorts should attempt to
      limit follow-up bias and offer opportunities to clarify determinants of SRC.

PMID- 29176506
TI  - Complication Rates After Total Hip and Knee Arthroplasty in Patients With
      Hepatitis C Compared With Matched Control Patients.
AB  - BACKGROUND: A paucity of data exists regarding long-term outcomes among patients
      with hepatitis C who undergo total hip arthroplasty (THA) and total knee
      arthroplasty (TKA). METHODS: We queried a database for patients with hepatitis C
      who underwent THA and TKA. We then identified their rates of several
      postoperative complications and compared them with the same rates among mutually
      exclusive matched control cohorts. RESULTS: Patients with hepatitis C who
      underwent THA and TKA had higher rates of infection, aseptic revision surgery,
      medical complications, and blood transfusion compared with matched control
      patients. DISCUSSION: Our findings suggest that patients with hepatitis C who
      undergo THA and TKA are at increased risk of experiencing several postoperative
      complications, which could mean a substantial increase in the cost of care.
      CONCLUSIONS: Further research is needed to establish quantifiable associations
      between hepatitis C and postoperative complications among patients with the
      disease who undergo total joint arthroplasty.

PMID- 29176507
TI  - Variables Affecting Return to Work After Spinal Surgery in a Non-workers'
      Compensation Population: A Retrospective Cohort Study.
AB  - INTRODUCTION: Return-to-work (RTW) outcomes following spine surgery are critical
      information for patients aspiring to return to employment following surgical
      correction. Among patients receiving workers' compensation (WC), spinal surgery
      has been repeatedly linked to poor RTW rates. However, among patients not
      receiving WC, the percentage of patients who return to employment is unclear.
      METHODS: We conducted a retrospective cohort study of 326 non-WC patients who
      underwent spinal surgery at two institutions. We determined RTW status and
      analyzed potential predictors of RTW status. RESULTS: Preoperative work status
      was the only markedly positive predictor of RTW status; patients who were working
      prior to their surgery were more likely to return to work after surgery. Patients
      with at least one comorbidity were less likely to return to employment. All other
      sociodemographic, surgery-related, and complication variables did not reach
      statistical significance. However, smoking status, short fusion, and cervical
      fusion were clinically relevant predictors of a negative RTW status. DISCUSSION:
      Among non-WC patients, employment before surgery was a positive predictor for RTW
      status. For patients with a positive comorbidity status, a lower likelihood of
      returning to employment is predicted. Randomized trials are needed to fully
      explore the effect of predictor variables on RTW status among non-WC patients.
      CONCLUSIONS: Patients not receiving WC who underwent spinal surgery had a high
      chance of returning to employment within 1 year if they had been working at least
      3 months before the date of surgery.

PMID- 29176508
TI  - Resting heart rate and the risk of hypertension and heart failure: a dose
      response meta-analysis of prospective studies.
AB  - BACKGROUND: Studies on the relationship of resting heart rate to the risks of
      hypertension and heart failure have been inconsistent, and the question as to
      whether there is a linear association between them is unanswered. OBJECTIVE: To
      evaluate this possible relationship, we carried out a dose-response meta-analysis
      of studies that looked at risks associated with resting heart rate and
      hypertension or heart failure. METHODS: We searched PubMed, Embase, CNKI and
      WanFang databases for articles published before 15 June 2017. A random-effect
      model was used to pool relative risks and 95% confidence intervals. Restricted
      cubic spline analysis was used to model the resting heart rate-hypertension and
      heart failure risk association. RESULTS: We identified 13 and 17 cohort studies
      for hypertension and heart failure, respectively. The risk for each disease,
      respectively, increased by 11% relative risk: 1.11 (95% confidence interval: 1.07
      1.15) and 19% relative risk: 1.19 (95% confidence interval: 1.13-1.25) for each
      10 beats-per-minute increment in resting heart rate. The relationship between
      resting heart rate and hypertension or heart failure was consistent in most
      subgroup analyses except for gender subgroups, with no significant association
      observed in the women subgroup. The results provide no evidence of a nonlinear
      association of elevated resting heart rate with hypertension and heart failure
      risk. CONCLUSION: Resting heart rate shows a linear positive association with the
      incidence of hypertension and heart failure.

PMID- 29176509
TI  - Doppler indexes of left ventricular systolic and diastolic function in relation
      to haemodynamic load components in a general population.
AB  - BACKGROUND: The contribution of central pulsatility to left ventricular (LV)
      dysfunction might be mediated by the haemodynamic loads of forward (Pf) and
      backward (Pb) pulse waves. We investigated the relation between echocardiographic
      indexes of LV function and pulsatile loads derived by wave separation analysis
      (WSA). METHODS: In 755 participants, we assessed LV dimensions, transmitral blood
      flow and mitral annular tissue velocities. We derived central pulse pressure
      (cPP) from radial tonometric recordings and calculated Pf, Pb and their ratio
      (reflection magnitude) using an automated, pressure-based WSA algorithm. Despite
      good quality recordings, WSA failed to derive Pf and Pb in 139 participants
      (18.4%), in particular in older women with unfavourable haemodynamics. Thus, our
      analysis included 616 participants (46.1% women; mean age, 49.2 years). RESULTS:
      Age and age explained most of the variance in cPP (36.9%), Pf (18.6%), Pb (41.5%)
      and reflection magnitude (36.7%; P < 0.0001) and altered the direct correlation
      between Pf and Pb (Pint < 0.0001). Haemodynamic loads were independently
      associated with sex, BMI, heart rate, mean arterial pressure, history of diabetes
      and use of antihypertensive drugs. In multivariable-adjusted analyses,
      transmitral velocities and E/e' ratio increased with higher cPP, Pf and Pb in men
      and women. We also observed an age-dependent association of LV radial strain with
      cPP, Pf and Pb. CONCLUSION: The commercial WSA algorithm holds limited clinical
      utility given its low feasibility in older participants with unfavourable
      haemodynamics. LV function indexes were similarly associated with Pf and Pb,
      favouring the use of the composite cPP for prediction of LV dysfunction.

PMID- 29176510
TI  - Cardiac function, myocardial mechano-energetic efficiency, and ventricular
      arterial coupling in normal pregnancy.
AB  - OBJECTIVE: To assess cardiac function, myocardial mechanoenergetic efficiency
      (MEE), and ventricular-arterial coupling (VAC) longitudinally during normal
      pregnancy, and to study if there was an association between cardiac structure and
      function, and fetal growth. METHODS: Cardiac structure and function, MEE, and
      ventricular-arterial coupling was assessed longitudinally in 52 healthy
      nulliparous women at 14, 24, and 34 weeks' gestation and 9-month postpartum.
      RESULTS: Left atrial diameter increased during pregnancy (30.41 +/- 3.59 mm in
      the nonpregnant state and 31.02 +/- 3.91, 34.06 +/- 3.58, and 33.9 +/- 2.97 mm in
      the first, second, and third trimesters, P < 0.001). Left ventricular mass
      increased 117.12 +/- 45.0 g in the nonpregnant state and 116.5 +/- 33.0, 126.9 +/
      34.5, 128.4 +/- 36 g in the first, second, and third trimesters (P < 0.001).
      Cardiac output increased from 3.4 +/- 1.2 l/min to 4.3 +/- 0.7 l/min in the
      second and third trimesters (P < 0.001). Diastolic function decreased as both E/A
      and e'/a' decreased during pregnancy (P < 0.05 and P < 0.001, respectively). MEE
      and VAC were retained during pregnancy. Heart rate was associated with birth
      weight centile in the first (r = 0.41, P = 0.002) and second (r = 0.46, P =
      0.002) trimester. CONCLUSION: The increase in cardiac output during normal
      pregnancy is obtained by an increase in heart rate, followed by structural
      cardiac changes. The impaired systolic function is accomplished by a deteriorated
      diastolic function. Despite these rapid changes, the myocardium manages to work
      efficient with a preserved MEE. Cardiac and arterial adaption to pregnancy seems
      to appear parallel as evidenced by a preserved VAC.

PMID- 29176512
TI  - Discordance in Pathologist Assessment of Endometrial Cancer is Informative While
      Level of Discordance of Molecular Classification Remains Unknown.

PMID- 29176511
TI  - Payer Policy Behavior Towards Opioid Pharmacotherapy Treatment in Ohio.
AB  - OBJECTIVE: Few studies examine how payers address the need for improved access to
      pharmacotherapy for opioid use disorders and the influence of environmental
      variables on access to opioid agonist and antagonist medications. METHOD: The 52
      Ohio Addiction Drug Abuse and Mental Health Services (ADAMHS) Boards that
      disburse funds for treatment services for the uninsured and underinsured were
      surveyed to assess coverage for opioid agonist and antagonist treatment
      medications. Analyses examined public health data on regional opioid addiction
      patterns, characteristics of the local health insurance market, and their
      associations with coverage for opioid addiction pharmacotherapy. RESULTS: Most
      (70%) of the 44 participating ADAMHS Boards paid for opioid treatment
      medications. For payment policy, all Boards required behavioral therapy to be
      provided in conjunction with opioid agonist or opioid antagonist therapy, and 27%
      of the Boards limited length of a buprenorphine therapy regimen. Higher local
      opioid treatment admission rates were associated with higher rates of Board
      funding for opioid treatment pharmacotherapy. Environmental variables (eg,
      overdose fatality rates or the behaviors of private insurance payers) were not
      associated with ADAMHS support for opioid agonist or antagonist medication.
      CONCLUSIONS: The analysis highlights the policy preferences of these payers.
      Follow-up studies should examine the payer decision-making processes,
      preferences, and attitudes that affect support for pharmacotherapy for opioid
      dependence.

PMID- 29176513
TI  - Endocrine therapy in ovarian cancer: where do we stand?
AB  - PURPOSE OF REVIEW: Hormonal factors play a pivotal role in epithelial ovarian
      tumorigenesis and steroid receptor expression has been associated with epithelial
      ovarian cancer (EOC) response and survival in recent studies. However, the degree
      of activity of endocrine therapy overall and by specific agents remains unclear.
      The purpose of this work is to summarize the evidence provided by the recent
      literature on the effectiveness of endocrine treatment for advanced EOC. RECENT
      FINDINGS: The results of 53 trials of different endocrine therapies in EOC
      indicate a clinical benefit of 41% [95% confidence interval (CI), 0.34-0.48],
      with a trend for a higher benefit in those with estrogen receptor (ER) + and/or
      progesteron receptor (PgR) + tumors. Moreover, the odd ratio for death showed a
      reduced mortality with endocrine regimens (0.69, 95% CI, 0.50-0.97), with a
      propensity for a better outcome in first-line and low-grade tumors. SUMMARY: We
      suggest that ER and PgR have a predictive role and their inhibition by endocrine
      therapy may be a treatment option for EOC. Randomized clinical trials in the
      first-line treatment of advanced hormone receptor positive EOC are warranted
      given the potential cost effectiveness of this approach.

PMID- 29176514
TI  - Measuring quality of life in individuals with Parkinson's disease attending a
      self-help club: cross-sectional study in Hungary.
AB  - The prevalence of Parkinson's disease (PD) increases with aging. The aim of our
      cross-sectional study was to measure the quality of life of PD patients attending
      a self-help 'PD club' and to evaluate the potential positive effect of club life
      on quality of life. Data collection was carried out using questionnaires (PDQ-39,
      Hungarian version). Altogether, 101 individuals with clinically diagnosed PD were
      included, and finally 98 persons' data were analyzed. Among the eight dimensions,
      the highest score was found in 'bodily discomfort' and the lowest in 'social
      support'. The overall tendency of the results was similar to another Hungarian
      study, but the scores in all dimensions were significantly lower in our
      participants. These positive results seem to correlate with attending the 'PD
      club', indicating the potential beneficial effect of patients' organizations on
      promoting mental health.

PMID- 29176515
TI  - Pet Peeves and Other Annoyances: An Editor's Perspective.

PMID- 29176516
TI  - Journal of Forensic Nursing 2016 Articles of the Year.

PMID- 29176518
TI  - Lessons Learned From iCare: A Postexamination Text-Messaging-Based Program With
      Sexual Assault Patients.
AB  - BACKGROUND: Although beneficial, few sexual assault patients seek follow-up
      healthcare or counseling after a medical forensic examination. Mobile technology
      interventions may help patients engage in postcare, but there is a dearth of
      research on patients' utilization of these interventions. The current study
      examines patients' engagement with a 4-week postassault text message program
      (iCare), which assessed patients' safety and well-being, if they needed
      assistance with accessing nonoccupational postexposure prophylaxis, or scheduling
      appointments for follow-up pregnancy and sexually transmitted infection testing,
      and their experience with the criminal justice system. METHODS: This pilot study
      collected data from 40 adult patient records and texting communications between
      the nurse and patients. We utilized descriptive statistics to examine patient
      utilization of the program. RESULTS: Sixty-five percent of the patients responded
      at least once during the program, but only two responded to every text. Nearly a
      quarter of the patients (22.5%) requested the texts to stop before the end of the
      program. A larger portion of the patients (42.5%) did not opt out but stopped
      replying by the third message. The program appeared to be helpful for increasing
      the amount of communication between the nurse and the patient, but patients
      rarely utilized the nurse's offers of assistance (e.g., counseling, advocacy).
      DISCUSSION: Text interventions appear to be effective for relaying information
      but may be limited for increasing postexamination service utilization for sexual
      assault patients. Future research should examine areas of patient needs in the
      weeks and months postexamination that can be addressed in text interventions.

PMID- 29176519
TI  - Risk Factors for Women Being Under the Influence of Alcohol Compared With Other
      Illicit Substances at the Time of Committing Violent Crimes.
AB  - PURPOSE: We investigated women under the influence of alcohol compared with other
      illicit substances at the time of committing a crime to identify predictors of
      being under the influence of alcohol and female-enacted crime. METHODS: Analyses
      of data, obtained from private interviews and examinations of female prison
      inmates, included regression analyses exploring predictors of being under the
      influence of alcohol at the time of the crime and predictors of violent crime. In
      addition, a reanalysis of a previously reported model, predicting conviction of a
      violent crime, was conducted including a new variable, being under the influence
      of alcohol at the time of the crime. RESULTS: Those under the influence of
      alcohol at the time of their crime had experienced greater nonfamilial childhood
      sexual abuse and traumatic brain injuries with loss of consciousness predating
      their crime. They were more likely to have committed a violent, rather than
      nonviolent, crime compared with those under the influence of other substances,
      with the latter being not significantly different for those not under the
      influence of any substance. Being under the influence of alcohol increased the
      risk of committing a violent crime, adjusting for other predictors of female
      violence. CONCLUSION: Women under the influence of alcohol are at a greater risk
      for committing violent crimes than those under the influence of other substances.
      Female nonfamilial childhood sexual abuse and traumatic brain injury victims were
      at a higher risk for being under the influence of alcohol, in comparison with
      other substances, at the time of committing a violent crime.

PMID- 29176520
TI  - Baccalaureate Nursing Students' Perceptions Regarding Autopsy Experiences.
AB  - PURPOSE: Since 2012, a medical-surgical nursing course at a midsized state
      university has provided the opportunity for students to view autopsies with a
      board-certified forensic pathologist. The autopsies are performed at a midsized
      hospital relatively close to the campus. The purpose of this study was to
      discover nursing students' perceptions that emerged during the autopsy
      experience. METHODS: A convenience sample of 23 baccalaureate nursing students
      took part in the autopsy experience over a 4-month period. Archival data from an
      online, anonymous questionnaire, completed after the experience, were reviewed
      and subjected to qualitative analysis. This study was approved by the
      university's institutional review board. RESULTS: Rich data emerged regarding the
      students' experiences, including emotional, psychological, and knowledge-based
      perceptions. CONCLUSION: Autopsies are important learning tools for nursing
      students, especially those who go into advanced practice nursing and forensic
      nursing. Anatomy, physiology, and pathophysiology are essential for students to
      understand as they learn about medical-surgical nursing concepts. Unique
      emotional characteristics of the students and cause of death of the deceased
      influenced how some students viewed the autopsy experience. Students reported
      that processing and debriefing activities were important after viewing autopsies
      and should be encouraged.

PMID- 29176521
TI  - Reflections on Forensic Nursing: An Interview With Virginia A. Lynch.

PMID- 29176522
TI  - Global Voyeurism or Sustainable Ethical Practice.

PMID- 29176523
TI  - PHOTODYNAMIC THERAPY WITH VERTEPORFIN PLUS INTRAVITREAL BEVACIZUMAB FOR
      CIRCUMSCRIBED CHOROIDAL HEMANGIOMA: 4 YEARS OF FOLLOW-UP.
AB  - PURPOSE: To report the anatomical and functional response of combined
      photodynamic therapy and intravitreal injection of bevacizumab in a patient with
      symptomatic circumscribed choroidal hemangioma. METHODS: The patient received a
      single-session full-fluence photodynamic therapy immediately followed by an
      intravitreal injection of bevacizumab (1.25 mg/0.05 mL). RESULTS: One week after
      combined therapy, an improvement of best-corrected visual acuity from count
      fingers to 20/60 and a significant decrease in subretinal fluid were noted. One
      month later, we observed decreased leakage on fluorescein angiography in all
      phases of the study. Three months after treatment, the best-corrected visual
      acuity improved to 20/25 and spectral domain optical coherence tomography scans
      showed return to normal foveal architecture with no subretinal fluid and
      completely flat tumor. These findings were maintained during 4 years of follow
      up. CONCLUSION: Combination therapy was associated with a rapid and persistent
      resolution of subretinal fluid, improvement of best-corrected visual acuity, and
      visual stability at 4 years of follow-up.

PMID- 29176524
TI  - NOVEL CASE OF CLOSTRIDIUM PERFRINGENS ENDOPHTHALMITIS AFTER ANTI-VASCULAR
      ENDOTHELIAL GROWTH FACTOR INJECTION.
AB  - INTRODUCTION: Endophthalmitis after anti-vascular endothelial growth factor
      injection is a rare complication but may lead to rapid destruction of structures
      within the eye. Infection with Clostridium perfringens has not previously been
      reported in this context. CASE REPORT: A 90-year-old woman presented with
      endophthalmitis of the right eye, 2 days after an intravitreal injection of
      ranibizumab. Initial examination showed a high intraocular pressure, refractive
      to topical treatment, reduced vision, and a hypopyon. Gram stain showed a Gram
      positive bacillus, which was identified as C. perfringens. Despite the use of
      intravitreal and intravenous antibiotics, the patient went on to develop cornea
      scleral melt of the right eye. She required an evisceration on the fifth day
      after ranibizumab. CONCLUSION: This case describes a unique and virulent pathogen
      leading to globe loss after an anti-vascular endothelial growth factor injection.
      C. perfringens, naturally living in feces or soil, is more commonly associated
      with dirty traumatic open-globe injuries. However, it is an important pathogen to
      consider when there is rapid destruction of eye structures associated with
      endophthalmitis. Based on a root cause analysis of this case, our department has
      introduced patient information leaflets on hand hygiene to educate patients
      having intraocular injections.

PMID- 29176525
TI  - NONHEREDITARY IDIOPATHIC FOVEAL RETINOSCHISIS ASSOCIATED WITH NEW-ONSET
      PROLIFERATIVE DIABETIC RETINOPATHY.
AB  - PURPOSE: To present a case of idiopathic foveal retinoschisis in a patient with
      new-onset proliferative diabetic retinopathy. METHODS: Single case report.
      RESULTS: A 64-year-old African American man with Type 2 diabetes mellitus
      presented for a routine annual diabetic eye examination with mildly blurred
      vision at near and distance in the right eye. Fluorescein angiography
      demonstrated optic nerve leakage consistent with neovascularization of the disk
      but no leakage on or around the macula in the right eye. Optical coherence
      tomography demonstrated peripapillary macular retinoschisis within the outer
      plexiform layer without optic disk pit, epiretinal membrane, or diabetic
      tractional membrane. He underwent pan-retinal photocoagulation in the right eye;
      his acuity and schisis remained unchanged at 6-month follow-up. CONCLUSION: This
      is the first reported case of idiopathic acquired macular schisis with new-onset
      nontractional proliferative diabetic retinopathy in the same eye.

PMID- 29176526
TI  - MACULAR HOLE FORMATION AFTER PARS PLANA VITRECTOMY FOR PRIMARY VITREORETINAL
      LYMPHOMA.
AB  - PURPOSE: To report a case of primary vitreoretinal lymphoma in which a macular
      hole developed after a diagnostic pars plana vitrectomy. METHODS: A retrospective
      interventional case report. RESULTS: A 65-year-old woman presented with worsening
      vision in the left eye. Fundus examination showed vitreous haze and multifocal,
      yellow-white infiltrates in the retina and under the retinal pigment epithelium
      in the left eye. She underwent a diagnostic pars plana vitrectomy in that eye.
      Undiluted vitreous specimen showed an increased interleukin-10 level (1,470
      pg/mL) with an elevated interleukin-10 to interleukin-6 ratio of 15.1; cytologic
      analysis of the vitreous showed atypical lymphoid cells with large irregular
      nuclei and scanty cytoplasm. The retinal and sub-retinal pigment epithelial
      infiltrates responded well to intravitreal methotrexate injections, but a macular
      hole developed in the left eye. The second pars plana vitrectomy with internal
      limiting membrane peeling and 20% sulfur hexafluoride gas tamponade successfully
      closed the macular hole. CONCLUSION: Macular hole closure can be accomplished in
      eyes receiving intravitreal methotrexate injections for treating primary
      vitreoretinal lymphoma.

PMID- 29176527
TI  - CAT SCRATCH DISEASE IMITATING A TOXOCARA GRANULOMA OF THE OPTIC DISK.
AB  - PURPOSE: The study reports an unusual presentation of a young female patient
      presenting with a granulomatous posterior pole mass and profound vision loss
      secondary to infection with Bartonella henselae. METHODS: A single case report in
      a child. RESULTS: An 8-year-old female presented with a recent history of flu
      like illness associated with profound vision loss, panuveitis and leukocoria in
      the left eye. She was found to have a posterior granulomatous mass associated
      with an exudative retinal detachment presumed as a toxocara granuloma. Magnetic
      Resonance Imaging ruled out retinoblastoma. Lab work done was negative for
      toxocariasis and positive for Bartonella henselae titers. She was treated for Cat
      Scratch Disease (CSD) with steroids and azithromycin. With treatment, the
      inflammation and exudative retinal detachment resolved, however, the patient had
      no improvement in visual acuity. CONCLUSIONS: Young patients presenting with
      leukocoria need a full work up, which includes ruling out retinoblastoma. CSD can
      present as a granulomatous mass similar to toxocariasis, which can rarely lead to
      debilitating and irreversible vision.

PMID- 29176528
TI  - PARACENTRAL ACUTE MIDDLE MACULOPATHY IN A PERIVENULAR FERN-LIKE DISTRIBUTION WITH
      EN FACE OPTICAL COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To report a case of central retinal vein occlusion resulting in a
      perivenular pattern of paracentral acute middle maculopathy lesions best
      identified with en face optical coherence tomography (OCT). METHODS:
      Retrospective case report. Optos ultra-widefield fluorescein angiography,
      spectral domain OCT, en face OCT, and OCT angiography were performed. RESULTS: A
      41-year-old man presented with decreased vision in the right eye for 2 weeks.
      Funduscopic examination of the affected right eye was notable for subtle retinal
      whitening in the macula, mild retinal venous dilation and tortuosity, and few
      scattered retinal dot and blot hemorrhages consistent with an acute central
      retinal vein occlusion. Widefield fluorescein angiography demonstrated delayed
      arterial and venous filling but no evidence of significant peripheral retinal
      vascular ischemia. En face OCT segmented at the inner nuclear layer illustrated a
      remarkable and precise perivenular distribution of fern-like paracentral acute
      middle maculopathy with periarterial sparing, whereas en face OCT segmented at
      the outer nuclear layer demonstrated florid cystoid macular edema. At 6-week
      follow-up, OCT demonstrated patchy areas of atrophic inner nuclear layer and
      spontaneous resolution of the cystoid macular edema. Optical coherence tomography
      angiography at the level of the deep capillary plexus illustrated remarkable flow
      reduction of the deep capillary plexus in mainly a perivenular distribution.
      CONCLUSION: The authors report a case of a central retinal vein occlusion with
      mild retinal findings associated with a remarkable perivenular pattern of
      paracentral acute middle maculopathy with en face OCT. Follow-up OCT angiography
      demonstrated significant flow reduction of the deep capillary plexus in a
      perivenular pattern. The perivenular pattern of paracentral acute middle
      maculopathy lesions with en face OCT can be an important finding suggestive of a
      central retinal vein occlusion.

PMID- 29176529
TI  - ATYPICAL PERIPAPILLARY INNER RETINOSCHISIS IN STELLATE NONHEREDITARY IDIOPATHIC
      FOVEOMACULAR RETINOSCHISIS.
AB  - PURPOSE: To describe an atypical presentation of a patient with stellate
      nonhereditary idiopathic foveomacular retinoschisis with peripapillary
      retinoschisis of multiple layers. METHODS: Complete ophthalmic examination
      including dilated extended ophthalmoscopy, fluorescein angiography, optical
      coherence tomography, optical coherence tomography angiography, and wide-field
      fundus photography. RESULTS: A 36-year-old Chinese American woman with mild
      myopia and good visual acuity (20/20) exhibited macular splitting of the outer
      plexiform layer on spectral domain optical coherence tomography with an attached
      hyaloid in her left eye. Peripheral spectral domain optical coherence tomography
      also demonstrated peripapillary and midperipheral inner retinoschisis, involving
      the outer plexiform layer and inner retina. The right eye was unremarkable. The
      diagnosis of stellate nonhereditary idiopathic foveomacular retinoschisis was
      made because of a lack of other associated ocular conditions and no family
      history of retinoschisis. CONCLUSION: Stellate nonhereditary idiopathic
      foveomacular retinoschisis is a recently described and uncommon cause of
      foveomacular retinoschisis in myopic women with good visual acuity. Recent
      evidence suggests that peripheral imaging is key in identifying other findings,
      including midperipheral or peripapillary inner retinoschisis, involving the outer
      plexiform layer and the inner retina. Our patient may represent a variant of
      stellate nonhereditary idiopathic foveomacular retinoschisis that can be
      characterized by multilayer peripapillary retinoschisis.

PMID- 29176530
TI  - A 9-YEAR-OLD GIRL WITH ACUTE MACULAR NEURORETINOPATHY.
AB  - PURPOSE: To report the clinical findings of the youngest confirmed case of acute
      macular neuroretinopathy to the best of our knowledge. METHODS: A 9-year-old
      patient describing a paracentral scotoma with a normal clinical examination and
      normal fluorescein angiography. RESULTS: Initial fundus examination was
      unremarkable. Fluorescein angiography findings showed no abnormalities but
      scotoma was confirmed using Amsler grid. Optical coherence tomography showed a
      parafoveal hyperreflective band in the outer layers. Subsequent optical coherence
      tomography showed resolution of the pathology. CONCLUSION: Acute macular
      neuroretinopathy is a rare condition usually presented as paracentral scotomas.
      Optical coherence tomography and Amsler grid testing can be used for diagnosis
      and to monitor findings on follow-up until resolution.

PMID- 29176532
TI  - PARANEOPLASTIC VITELLIFORM MACULOPATHY ASSOCIATED WITH METASTATIC MELANOMA.
AB  - PURPOSE: To report a case of paraneoplastic vitelliform maculopathy in a patient
      with metastatic melanoma of unknown primary site. METHODS: Case report. Main
      outcome measures include funduscopic examination, fluorescein angiography, fundus
      autofluorescence, and spectral domain optical coherence tomography. RESULTS: A 44
      year-old man with a known history of metastatic melanoma was referred for
      ophthalmic evaluation because of bilateral vision loss. Funduscopic examination
      was remarkable for vitelliform maculopathy that was confirmed with fundus
      autofluorescence and spectral domain optical coherence tomography. CONCLUSION: We
      describe a rare case of paraneoplastic vitelliform maculopathy. There are many
      etiologies of acquired vitelliform retinal lesions in the retina. Multimodal
      retinal imaging, including fundus autofluorescence and spectral domain optical
      coherence tomography, can be best used to identify these lesions. A history of
      systemic metastatic melanoma should be ruled out in patients with vitelliform
      maculopathy.

PMID- 29176531
TI  - AUTOIMMUNE RETINOPATHY IN A PATIENT WITH A MISSENSE MUTATION IN PITPNM3.
AB  - PURPOSE: To describe a patient with a PITPNM3 missense mutation who developed
      late-onset autoimmune retinopathy. METHODS: Case report. RESULTS: An 85-year-old
      man presented with decreased vision, nyctalopia, and photoaversion after an
      uncomplicated cataract surgery. Multimodal retinal imaging revealed a scalloped
      pattern of atrophy and a ring of hyperautofluorescence in the perifoveal area on
      fundus autofluorescence. Spectral domain optical coherence tomography
      demonstrated loss of the ellipsoid band, along with outer retinal atrophy,
      sparing the fovea in both eyes. Full field electroretinogram revealed
      extinguished rod response and severely attenuated cone response. Antiretinal
      antibodies to 20-kDa and 125-kDa proteins were detected. Whole-exome sequencing
      revealed a heterozygous variant, c.2579T>C, p.(Ile860Thr) in PITPNM3, predicted
      to be severely damaging and deleterious to the protein structure and function.
      Over the course of 3 months, the patient experienced a rapid progression.
      Neoplastic workup was negative and he was started on immunosuppressive therapy
      for a presumed diagnosis of nonparaneoplastic autoimmune retinopathy. CONCLUSION:
      To the authors' knowledge, this is the first report of autoimmune retinopathy in
      a patient with PITPNM3 mutation. PITPNM3 has been previously shown to affect
      regulatory T cell function.

PMID- 29176533
TI  - IDIOPATHIC MULTIFOCAL CHOROIDITIS PRESENTING WITH A TRANSIENT PERIPAPILLARY WHITE
      RING.
AB  - PURPOSE: We describe with multimodal imaging the presentation and follow-up for a
      patient with idiopathic multifocal choroiditis and a transient peripapillary
      white ring. METHODS: Case report. RESULTS: A 39-year-old Asian woman was
      initially seen for an evaluation of lattice degeneration in 2015. Her medical
      history included Graves disease and psoriasis. Best-corrected visual acuity was
      20/25 in her right eye and 20/25 in her left eye. Ultra-widefield fundus
      autofluorescence imaging showed a curvilinear hyperautofluorescent line in her
      right eye. One year later, the patient returned complaining of floaters in her
      right eye for 1 month. Her visual acuity was unchanged. Funduscopic examination
      showed new inflammatory yellowish lesions in the right eye corresponding to
      hyperreflective sub-retinal pigment epithelium lesions on structural spectral
      domain optical coherence tomography. Fluorescein angiography showed corresponding
      late staining of these active lesions. Late-phase indocyanine green angiography
      showed multiple nummular hypocyanescent dots. Ultra-widefield fundus
      autofluorescence showed large areas of hyperautofluorescence. The patient was
      started on a 60-mg oral prednisone taper and demonstrated subsequent regression
      of the inflammatory lesions. Ten months later, the patient returned emergently
      with complaints of floaters in both eyes for 2 days and a new temporal scotoma in
      her left eye. Funduscopic examination demonstrated a white ring around the optic
      nerve of the left eye corresponding to a hyperautofluorescent lesion. Ultra
      widefield fundus autofluorescence showed new areas of hyperautofluorescence in
      both eyes. Structural spectral domain optical coherence tomography showed new sub
      retinal pigment epithelium inflammatory lesions and a disruption of the ellipsoid
      zone in both eyes. The patient was again treated with a 60-mg oral prednisone
      taper and demonstrated subsequent restoration of the ellipsoid zone. CONCLUSION:
      To our knowledge, this is the first report of a transient annular white ring
      occurring in a case of multifocal choroiditis. There was marked restoration of
      the disrupted ellipsoid zone after treatment with oral corticosteroids.

PMID- 29176534
TI  - IMMUNE RETINOPATHY ASSOCIATED WITH NIVOLUMAB ADMINISTRATION FOR METASTATIC NON
      SMALL CELL LUNG CANCER.
AB  - PURPOSE: To present a novel case of immune retinopathy associated with nivolumab
      therapy for non-small cell lung cancer. METHODS: Retrospective chart review.
      RESULTS: A 64-year-old woman presented with photoreceptor injury evidenced by
      hypoautofluorescent and hyperautofluorescent patches on fundus autofluorescence,
      loss of the ellipsoid zone on optical coherence tomography, and dysfunction of
      the rods and cones on electroretinogram. She had a history of Stage IV lung
      adenocarcinoma, treated with nivolumab, a checkpoint inhibitor. Serology testing
      was negative for paraneoplastic antibody panel, antirecoverin and antienolase
      antibodies, but positive for antiretinal antibodies against 30-kDa (carbonic
      anhydrase II), 35-kDa (GADPH), 38-kDA, 58-kDa (PKM2), and 112-kDa proteins.
      Cessation of the medication and high-dose oral steroids resulted in resolution of
      her symptoms and stability of ocular findings. CONCLUSION: The checkpoint
      inhibitors, including nivolumab, have significant ocular side effects. All
      patients receiving nivolumab should undergo a baseline comprehensive eye
      examination and should be counseled to seek medical attention immediately if
      visual changes occur.

PMID- 29176535
TI  - SPONTANEOUS IMPROVEMENT OF SYPHILIS CHORIORETINITIS: CASE REPORT AND REVIEW OF
      THE LITERATURE.
AB  - PURPOSE: To describe a case of spontaneous improvement of syphilis
      chorioretinitis and review the literature. METHODS: Case report and literature
      review of cases with untreated syphilis chorioretinitis. RESULTS: A 58-year-old
      man presented to the emergency department with counting fingers vision, normal
      fundus, and disruption of the outer retinal layers on optical coherence
      tomography of the right eye. Examination by a retina specialist 3 weeks later
      revealed visual acuity of 20/50 and partial restoration of outer retinal layers
      on optical coherence tomography. Workup showed positive serology for syphilis and
      human immunodeficiency virus. Treatment with intravenous penicillin resulted in
      further vision improvement. Literature review showed six cases of spontaneous
      improvement of syphilis chorioretinitis. CONCLUSION: Spontaneous improvement of
      syphilis chorioretinitis is possible. Clinicians should keep a high index of
      suspicion and consider syphilis chorioretinitis in diseases that affect the outer
      retina even with spontaneous improvement.

PMID- 29176536
TI  - PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH BILATERAL OPTIC DISK
      SWELLING AND MENINGITIS.
AB  - BACKGROUND/PURPOSE: To present a novel case of paracentral acute middle
      maculopathy associated with bilateral optic disk swelling. METHODS: Retrospective
      case report. RESULTS: A 67-year-old woman presented with sudden onset of central
      vision loss and subsequent bilateral optic disk edema, retinal vessel
      attenuation, and anterior uveitis. Cerebrospinal fluid analysis showed signs of
      inflammation. Spectral domain optical coherence tomography demonstrated the
      pathognomonic hyperreflectivity of the middle retinal layers consistent with
      paracentral acute middle maculopathy. Swept-source optical coherence tomography
      angiography with custom vessel analysis demonstrated a 18.3% decrease in the deep
      retinal vascular density and 2.4 times increase in absent flow area in the
      affected eye compared with the fellow eye. CONCLUSION: This case demonstrates a
      novel association between paracentral acute middle maculopathy and bilateral
      optic disk swelling secondary to central nervous system inflammation and possible
      infection. Although spectral domain optical coherence tomography is valuable in
      detecting paracentral acute middle maculopathy, optical coherence tomography
      angiography with vessel analysis can provide additional insight into the disease
      mechanism.

PMID- 29176537
TI  - NOVEL SURGICAL TECHNIQUE FOR INDUCING POSTERIOR VITREOUS DETACHMENT DURING PARS
      PLANA VITRECTOMY FOR PEDIATRIC PATIENTS USING A FLEXIBLE LOOP.
AB  - PURPOSE: Vitreoretinal surgical diseases in children are challenging because of
      the complex features of the vitreous, retina, and the interface between them.
      Posterior vitreous detachment is a crucial step during vitrectomy. To date,
      pharmacologic vitreolysis that liquefies the vitreous and disrupts the posterior
      hyaloid attachment to the retina has been studied. However, there are reports of
      unexplained adverse effects. We describe a case performed with a reproducible,
      safe and time-saving technique using a commercially available flexible loop for
      posterior vitreous detachment induction in a pediatric patient. METHODS: A 10
      year-old boy with previously treated retinopathy of prematurity undergoes a 25
      gauge pars plana vitrectomy for retina detachment repair. To achieve a posterior
      vitreous detachment, a flexible loop was used to grasp and pick the vitreoretinal
      interface around the optic nerve for dissection of the posterior hyaloid,
      followed by aspiration and cutting with the vitrectomy probe to complete the
      vitrectomy. RESULTS: At 3 months follow-up, total retinal reattachment was
      observed. The patient's vision improved from 20/400 to 20/150. CONCLUSION:
      Posterior vitreous detachment induction with a flexible loop instead of
      pharmacologic vitreolysis seems a promising tool as demonstrated in this clinical
      case. Further studies to demonstrate long-term safety and anatomical results are
      needed.

PMID- 29176538
TI  - VITREOUS TREPONEMAL ANTIBODY AS A SUPPLEMENTARY TEST TO SEROLOGY FOR THE
      CONFIRMATION OF SYPHILITIC CHORIORETINITIS.
AB  - PURPOSE: To report the novel application of nontreponemal and treponemal antibody
      to confirm diagnosis of ocular syphilis from vitreous samples. METHODS: Two
      distinct case reports emphasizing the importance of confirmatory vitreous
      treponemal antibody. Multimodal imaging of patients was also applied. RESULTS: We
      report two distinct cases with positive serum treponemal antibody but opposing
      vitreous treponemal antibody results. One case with a positive vitreous test
      responded well to antisyphilitic treatment. By contrast, a case with a negative
      vitreous result was changed to serpiginous choroiditis, eventually cured by
      immunomodulatory treatment. CONCLUSION: Intraocular fluid analysis of
      nontreponemal and treponemal antibody may play an important role in ruling out
      suspected ocular syphilis in settings without a polymerase chain reaction
      facility, especially immunocompromised patients who are at risk of multiple
      infections. Further studies are needed to establish the sensitivity and
      specificity of nontreponemal and treponemal antibody test on vitreous samples.

PMID- 29176539
TI  - Efficacy and Safety of Chemotherapy Combined with Stereotactic Radiotherapy in
      the Treatment of Nasopharyngeal Carcinoma.
AB  - BACKGROUND The aim of this study was to investigate the efficacy and safety of
      chemotherapy (CT) combined with stereotactic radiotherapy (SRT) in the treatment
      of nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS A total of 329 NPC
      patients without any previous treatment were included in this study between
      January 2009 and November 2013. These patients were divided into three groups: CT
      group (n=114), SRT group (n=109), and CT + SRT group (n=106). Contrast-enhanced
      nasopharyngeal computed tomography (CT)/magnetic resonance (MR) scan was
      performed on the third month after treatment. Short-term efficacy was evaluated
      according to the Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity
      was graded according to the Acute Radiation Morbidity Scoring Criteria (RTOG) and
      the World Health Organization (WHO) toxicity grading scale. Overall survival
      (OS), progression free survival (PFS), and incidence rate of acute toxicity
      (grade >=3) were calculated after a 24 month follow-up. RESULTS Total response
      rate of all patients was 85.41%. Compared with the CT group and the SRT group,
      the CT + SRT group showed a substantially improved efficacy in NPC treatment. The
      incidence rate of the acute toxicity in the CT + SRT group was slightly higher
      than in the CT group and the SRT group, but the difference was not statistically
      significant. No treatment-related deaths were observed. The CT + SRT group had
      the highest two-year OS and PFS, followed by the CT group and the SRT group.
      CONCLUSIONS It was shown that NPC patients treated with CT + SRT had better short
      and long-term efficacy than those treated with CT or SRT alone.

PMID- 29176540
TI  - The Effect of Oral Contraceptive Pills on the Macula, the Retinal Nerve Fiber
      Layer, and Choroidal Thickness.
AB  - BACKGROUND The aim of this study was to evaluate the effect of oral contraceptive
      pills (OCP) on the macula, the retinal nerve fiber layer (RNFL), and choroidal
      thickness (CT). MATERIAL AND METHODS A total of 24 healthy women taking
      monophasic OCP (3 mg drospirenone and 0.03 mg ethinylestradiol) for contraception
      only for at least one year were compared with a control group of 24 healthy women
      who were not taking an OCP. Optical coherence tomography (OCT) was used to
      evaluate the posterior ocular segments, and measurements were taken in the
      follicular phase (day 3) of the cycle in all women. RESULTS No disparity in terms
      of age and body mass index between the groups was observed (p=0.436, p=0.538,
      respectively). In comparison of the macular region and CT between groups, we
      found that all variables except foveal center thickness and CT were significantly
      thinner in the OCP group. Nasal and temporal inferior parts of the RNFL and
      average RNFL were significantly slimmer in the study group versus the control
      group (p=0.013, p=0.018, and p<0.001, respectively). CONCLUSIONS OCP resulted in
      several structural changes in the posterior ocular segment. Thus, women using OCP
      for more than one year may have some eye problems. Therefore, it OCT should be
      performed for these women. Further clinical trials researching long-period effect
      of OCP on the eyes are needed.

PMID- 29176541
TI  - Diffuse Peritoneal and Bowel Wall Infiltration by Light Chain-AL Amyloidosis with
      Omental Calcification Mimicking Abdominal Carcinomatosis - An Elderly Female with
      Incidental Finding of Light Chain Monoclonal Gammopathy of Undetermined
      Significance (LC-MGUS).
AB  - BACKGROUND Amyloidosis is the extracellular tissue deposition of plasma proteins,
      which after conformational changes, forms antiparallel beta pleated sheets of
      fibrils. Amyloid light-chain (AL) is a type of amyloidosis that is due to
      deposition of proteins derived from immunoglobulin (Ig) light chains.
      Gastrointestinal tract (GIT) involvement most often found in amyloid A (AA)
      amyloidosis type. There have been no reports of obstructive GIT AL amyloid
      patients having monoclonal gammopathy of undetermined significance (MGUS). Our
      case is the first case to show two coinciding conditions; one is the association
      of GIT AL amyloidosis with the incidental finding of a rare type of MGUS (LC
      MGUS) and the other is the radiologic presentation of GIT amyloidosis with
      omental calcification mimicking the GIT malignancy. CASE REPORT A 68-year-old
      female presented with symptoms of partial bowel obstruction, including
      intermittent diffuse abdominal pain and constipation. After computed tomography
      (CT) abdomen and pelvis, an exploratory laparotomy was needed because of
      suspicion of abdominal carcinomatosis due to diffuse omental calcification. The
      tissue sent for biopsy surprisingly showed AL amyloidosis. The patient did not
      report any systemic symptoms. Further workup was advised to inquire about the
      plasma cell dyscrasia which eventually turned into a very rare version of MGUS
      knows as light chain MGUS (LC-MGUS). Following adequate resection of the involved
      structures, the patient was then placed on chemotherapy and successfully went
      into remission. CONCLUSIONS This case report illustrates that in an era of
      evidence based medicine, it is important to show through case reports the
      association of GIT AL amyloidosis with LC-MGUS, as the literature on this topic
      is lacking. It also points to the importance of timely intervention that can
      greatly enhance, not only the only the chances of remission but also prevention
      of further complications such as malignant transformation.

PMID- 29176542
TI  - Diabetic Microagiopathy of Oral Mucosa Depends on Disease Duration and Therapy.
AB  - BACKGROUND Diabetes mellitus is a chronic degenerative systemic disease whose
      prevalence is increasing. This paper aims to evaluate the effects of diabetic
      microangiopathy, depending on its duration and the type of treatment
      administered, by using polarized light videocapillaroscopy of the oral mucosa.
      MATERIAL AND METHODS We enrolled 120 subjects: 60 healthy subjects and 60
      patients with diabetes mellitus. In turn, patients were divided into 3 subgroups
      according to the type of diabetes, the duration of the disease, and the type of
      treatment administered. A videocapillaroscopic examination of the oral mucosa was
      carried out on the diabetic and healthy subjects. RESULTS Changes in
      microcirculation were detected in diabetic patients: at the level of the labial,
      buccal, and lingual mucosa, the density of the loops is on average reduced; there
      is an increase in the length and the total diameter of the loops, while the
      average density of the periodontal capillaries is much higher. The most
      significant changes were noted in patients who had had type 1 diabetes for more
      than 10 years and had received insulin therapy. CONCLUSIONS This study, performed
      using polarized light videocapillaroscopy, which for the first time was used to
      analyze the capillaries of the oral mucosa in patients with diabetes, confirms
      the presence of changes that are instrumentally "objectifiable" and
      "quantifiable" through the videocapillaroscopic technique. Videocapillaroscopy
      can be a reliable method in the study and monitoring of complications in patients
      with type 1 and 2 diabetes mellitus.

PMID- 29176543
TI  - A Rare Case of Cerebellar Ataxia Due to Voltage-Gated Calcium Channel and
      Glutamic Acid Decarboxylase Autoantibodies.
AB  - BACKGROUND Autoimmune cerebellar ataxia can be paraneoplastic in nature or can
      occasionally present without evidence of an ongoing malignancy. The detection of
      specific autoantibodies has been statistically linked to different etiologies.
      CASE REPORT A 55-year-old African-American woman with hypertension and a past
      history of morbid obesity and uncontrolled diabetes status post gastric bypass
      four years prior to the visit (with significantly improved body mass index and
      hemoglobin A1c controlled at the time of the clinical encounter) presented to the
      office complaining of gradual onset of unsteadiness and recurrent falls for the
      past three years, as well as difficulties coordinating routine daily activities.
      The neurologic exam showed moderate dysarthria and ataxic gait with bilateral
      dysmetria and positive Romberg test. Routine laboratory test results were only
      remarkable for a mild elevation of erythrocyte sedimentation rate, and most
      laboratory and imaging tests for common causes of ataxia failed to demonstrate an
      etiology. Upon further workup, evidence of anti-voltage-gated calcium channel and
      anti-glutamic acid decarboxylase antibody was demonstrated. She was then treated
      with intravenous immunoglobulins with remarkable clinical improvement.
      CONCLUSIONS We present a case of antibody-mediated ataxia not associated with
      malignancy. While ataxia is rarely related to autoantibodies, in such cases it is
      critical to understand the etiology of this disabling condition in order to treat
      it correctly. Clinicians should be aware of the possible association with
      specific autoantibodies and the necessity to rule out an occult malignancy in
      such cases.

PMID- 29176544
TI  - PI3K-Akt Signal Transduction Molecules Maybe Involved in Downregulation of
      Erythroblasts Apoptosis and Perifosine Increased Its Apoptosis in Chronic
      Mountain Sickness.
AB  - BACKGROUND Chronic mountain sickness (CMS) has a higher incidence in the plateau
      region. The one of its principal characters is excessive erythrocytosis. The PI3K
      Akt pathway plays an important role in the process of erythropoiesis, and could
      downregulate apoptosis by regulating apoptosis-related molecules. In this paper,
      we explored the change in apoptosis of erythroblasts and the effect of the PI3K
      Akt signal pathway on erythroblasts apoptosis in CMS. MATERIAL AND METHODS A
      total of 22 CMS and 20 non-CMS participants were involved in this study. Bone
      marrow mononuclear cells were cultured and treated with celecoxib and perifosine
      in vitro for 72 hours. The apoptotic rate, the mRNA expressions of Akt, Bcl-xl,
      and caspase-9, and the protein expressions of Akt, p-Akt, Bcl-xl, and caspase-9
      were determined by flow cytometry, quantitative RT-PCR, and western-blot
      technique. RESULTS The apoptotic rate of cultured erythroblasts was lower in the
      CMS group than in the non-CMS group. It was increased after perifosine
      intervention. The mRNA and protein expressions of Akt and Bcl-xl were higher and
      caspase-9 was lower in the CMS group than the non-CMS group. Perifosine induced
      decreased Bcl-xl mRNA and proteins and p-Akt proteins, and increased caspase-9
      mRNA and proteins in vitro. In the CMS group, the hemoglobin concentration was
      correlated with apoptotic rate negatively and with Bcl-xl mRNA positively in
      erythroblasts; the erythroblasts apoptotic rate was negatively associated with
      the Akt mRNA and Bcl-xl mRNA. CONCLUSIONS The erythroblasts apoptosis was
      downregulated and the PI3K-Akt signal pathway appeared to be involved in the
      mechanism of decreased erythroblasts apoptosis in CMS.

PMID- 29176545
TI  - A Prediction Model with a Combination of Variables for Diagnosis of Lung Cancer.
AB  - BACKGROUND Multivariate models with a combination of variables can predict
      disease more accurately than a single variable employed alone. We developed a
      logistic regression model with a combination of variables and evaluated its
      ability to predict lung cancer. MATERIAL AND METHODS The exhaled breath from 57
      patients with lung cancer and 72 healthy controls without cancer was collected.
      The VOCs of exhaled breath were examined qualitatively and quantitatively by a
      novel electronic nose (Z-nose4200 equipment). The VOCs in the 2 groups were
      compared using the Mann-Whitney U test, and the baseline data were compared
      between the 2 groups using the chi-square test or ANOVA. Variables from VOCs and
      baseline data were selected by stepwise logistic regression and subjected to a
      prediction model for the diagnosis of lung cancer as combined factors. The
      receiver operating characteristic (ROC) curve was used to evaluate the predictive
      ability of this prediction model. RESULTS Nine VOCs in exhaled breath of lung
      cancer patients differed significantly from those of healthy controls. Four
      variables - age, hexane, 2,2,4,6,6-pentamethylheptane, and 1,2,6
      trimethylnaphthalene - were entered into the prediction model, which could
      effectively separate the lung cancer samples from the control samples with an
      accuracy of 82.8%, a sensitivity of 76.0%, and a specificity of 94.0%.
      CONCLUSIONS The profile of VOCs in exhaled breath contained distinguishable
      biomarkers in the patients with lung cancers. The prediction model with 4
      variables appears to provide a new technique for lung cancer detection.

PMID- 29176546
TI  - Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a
      Mouse Model of Allergic Airway Inflammation.
AB  - BACKGROUND Migration of leukocytes into airways is the hallmark of allergic
      asthma. The aim of this study was to target the pathological process using
      pantethine, a pleiotropic natural compound which has been recently shown to down
      regulate chemokine-driven T cell migration. MATERIAL AND METHODS Mice were
      sensitized to the Leishmania LACK antigen, then treated or not treated with
      pantethine and exposed to LACK or saline aerosol. After sacrifice of the animals,
      cells in the bronchoalveolar lavage were analyzed and inflammatory parameters
      were determined to evaluate inflammation seriousness. RESULTS As compared to
      untreated animals, pantethine-treated animals displayed a moderated response to
      the allergen, as documented by decreased infiltration of inflammatory cells (all
      types), in addition to reduced levels of lung Th2 cytokines and circulating LACK
      specific IgE. CONCLUSIONS These data reveal the potential therapeutic importance
      of pantethine to moderate allergic asthma pathology. The compound has been
      previously shown to exert a broad range of protective activity in animals and in
      humans, with few or no adverse effects.

PMID- 29176547
TI  - Protective Role of TNIP2 in Myocardial Injury Induced by Acute Pancreatitis and
      Its Mechanism.
AB  - BACKGROUND Aberrant regulation of nuclear factor-kappaB (NF-kappaB) and the
      signaling pathways that regulate its activity have been found to be involved in
      various pathologies, particularly cancers, as well as inflammatory and autoimmune
      diseases. Acute pancreatitis (AP) is a complex pathological process, depending on
      autodigestion caused by premature activation of zymogens. This study aimed to
      investigate the effect of high expression of TNIP2 gene on AP and AP-induced
      myocardial injury. MATERIAL AND METHODS To investigate the effect of TNIP2 on AP
      and AP-induced myocardial injury, we established an AP cell model and rat model.
      HE staining was applied for histological examination. ELISA was used to determine
      the level of pro-inflammatory cytokines (TNF-alpha and IL-6) and myocardial
      injury markers (LDH and CK-MB). QRT-PCR and Western blot analysis were performed
      to determine the mRNA and protein level of related genes, respectively. RESULTS
      We found that the protein level of TNIP2 was relatively higher in the normal
      AR42J cells. At 4 h after stimulating with cerulein, the protein level of TNIP2
      decreased, reached a minimum at 8 h, and then gradually increased. We also found
      that TNIP2 was correlated with the activation of NF-kappaB in cerulein-stimulated
      AR42J cells, and TNIP2 over-expression inhibited the inflammatory response caused
      by cerulein. Moreover, our results suggest that TNIP2 over-expression relieved
      the cerulein-triggered inflammatory response and AP-induced myocardial injury in
      mice. CONCLUSIONS TNIP2 was shown to exert a protective effect on AP and AP
      induced myocardial injury.

PMID- 29176548
TI  - Comparison through a prospective and randomized study of two replenishment
      methods at polyvalent hospitalization units with two-bin storage systems
AB  - OBJECTIVE: Two-bin storage systems increase nursing staff satisfaction and
      decrease inventories, but the implications that logistic staff would determine
      the needs of replenishment are unknown. This study aimed to evaluate whether
      entrust to logistics staff this responsibility at the polyvalent hospitalization
      units with two-bin storage is associated with higher risk of outstanding orders.
      METHODS: This was a prospective randomized experiment whit masking. Outstanding
      orders were considered variable response, those corresponding to assessments of
      the logistics staff were included in the control group and those corresponding to
      the nursing staff in the control group. Concordance between observers was
      analyzed using the Bland-Altman method; the difference between groups, with the U
      of Mann-Whitney and the cumulative incidence of outstanding orders and their
      relative risk was calculated. RESULTS: The mean amount requested by the logistic
      and nursing staff was 29.9 (SD:167.4) and 36 (SD:190) units respectively, the
      mean difference between observers was 6.11 (SD:128.95) units and no significant
      differences were found between groups (p = 0.430). The incidence of outstanding
      orders was 0.64% in the intervention group and 0.15% in the control group; the
      relative risk, 2.31 (0.83 - 6.48) and the number of cases required for an
      outstanding order, 516. CONCLUSIONS: Outstanding order relative risk is not
      associated with the category of the staff that identifies the replenishment needs
      at the polyvalent hospitalization units.

PMID- 29176549
TI  - Origami silicon optoelectronics for hemispherical electronic eye systems.
AB  - Digital image sensors in hemispherical geometries offer unique imaging advantages
      over their planar counterparts, such as wide field of view and low aberrations.
      Deforming miniature semiconductor-based sensors with high-spatial resolution into
      such format is challenging. Here we report a simple origami approach for
      fabricating single-crystalline silicon-based focal plane arrays and artificial
      compound eyes that have hemisphere-like structures. Convex isogonal polyhedral
      concepts allow certain combinations of polygons to fold into spherical formats.
      Using each polygon block as a sensor pixel, the silicon-based devices are shaped
      into maps of truncated icosahedron and fabricated on flexible sheets and further
      folded either into a concave or convex hemisphere. These two electronic eye
      prototypes represent simple and low-cost methods as well as flexible optimization
      parameters in terms of pixel density and design. Results demonstrated in this
      work combined with miniature size and simplicity of the design establish
      practical technology for integration with conventional electronic devices.

PMID- 29176551
TI  - Discovery of novel choline acetyltransferase inhibitors using structure-based
      virtual screening.
AB  - Alzheimer disease and related dementias are major challenges, demanding urgent
      needs for earliest possible diagnosis to optimize the success rate in finding
      effective therapeutic interventions. Mounting solid scientific premises point at
      the core acetylcholine-biosynthesizing cholinergic enzyme, ChAT as a legitimate
      in vivo target for developing positron emission tomography biomarker for early
      diagnosis and/or monitoring therapeutic responses in the neurodegenerative
      dementias. Up-to-date, no PET tracer ligands for ChAT are available. Here we
      report for the first time a novel hierarchical virtual screening approach on a
      commercial library of ~300,000 compounds, followed by in vitro screening of the
      hits by a new High-Throughput ChAT assay. We report detailed pharmacodynamic data
      for three identified selective novel ChAT ligands with IC50 and K i values
      ranging from ~7 to 26 uM. In addition, several novel selective inhibitors of the
      acetylcholine-degrading enzymes, AChE and BuChE were identified, with one of the
      compounds showing an IC50-value of ~6 uM for AChE. In conclusion, this report
      provides an excellent starting platform for designing and optimizing potent and
      selective ChAT ligands, with high potential as PET-imaging probe for early
      diagnosis of AD, and related dementias, such as Down's syndrome and Lewy body
      disorders.

PMID- 29176550
TI  - A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia.
AB  - Hypoxia occurs when limited oxygen supply impairs physiological functions and is
      a pathological hallmark of many diseases including cancer and ischemia. Thus,
      detection of hypoxia can guide treatment planning and serve as a predictor of
      patient prognosis. Unfortunately, current methods suffer from invasiveness, poor
      resolution and low specificity. To address these limitations, we present Hypoxia
      Probe 1 (HyP-1), a hypoxia-responsive agent for photoacoustic imaging. This
      emerging modality converts safe, non-ionizing light to ultrasound waves, enabling
      acquisition of high-resolution 3D images in deep tissue. HyP-1 features an N
      oxide trigger that is reduced in the absence of oxygen by heme proteins such as
      CYP450 enzymes. Reduction of HyP-1 produces a spectrally distinct product,
      facilitating identification via photoacoustic imaging. HyP-1 exhibits selectivity
      for hypoxic activation in vitro, in living cells, and in multiple disease models
      in vivo. HyP-1 is also compatible with NIR fluorescence imaging, establishing its
      versatility as a multimodal imaging agent.

PMID- 29176552
TI  - Hall conductance for open two-band system beyond rotating-wave approximation.
AB  - The response of the open two-band system to external fields would in general be
      different from that of a strictly isolated one. In this paper, we systematically
      study the Hall conductance of a two-band model under the influence of its
      environment by treating the system and its environment on equal footing. In order
      to clarify some well-established conclusions about the Hall conductance, we do
      not use the rotating wave approximation (RWA) in obtaining an effective
      Hamiltonian. Specifically, we first derive the ground state of the whole system
      (the system plus the environment) beyond the RWA, then calculate an analytical
      expression for Hall conductance of this open system in the ground state. We apply
      the expression to two examples, including a magnetic semiconductor with Rashba
      type spin-orbit coupling and an electron gas on a square two-dimensional lattice.
      The calculations show that the transition points of topological phase are robust
      against the environment. Our results suggest a way to the controlling of the
      whole system response, which has potential applications for condensed matter
      physics and quantum statistical mechanics.

PMID- 29176553
TI  - Notoginsenoside R1 Alleviates Oxygen-Glucose Deprivation/Reoxygenation Injury by
      Suppressing Endoplasmic Reticulum Calcium Release via PLC.
AB  - As documented in our previous study, notoginsenoside R1 (NGR1) can inhibit neuron
      apoptosis and the expression of endoplasmic reticulum (ER) stress-associated pro
      apoptotic proteins in hypoxic-ischemic encephalopathy. Recent evidence indicates
      that the Phospholipase C (PLC)/inositol 1,4,5-trisphosphate receptor (IP3R) is
      important for the regulation of Ca2+ release in the ER. Ca2+ imbalance can
      stimulate ER stress, CAMKII, and cell apoptosis. The purpose of this study was to
      further investigate the neuroprotective effect of NGR1 and elucidate how NGR1
      regulates ER stress and cell apoptosis in the oxygen-glucose
      deprivation/reoxygenation (OGD/R) model. Cells were exposed to NGR1 or the PLC
      activator m-3M3FBS. Then, IP3R- and IP3-induced Ca2+ release (IICR) and
      activation of the ER stress and CaMKII signal pathway were measured. The results
      showed that NGR1 inhibited IICR and strengthened the binding of GRP78 with PERK
      and IRE1. NGR1 also alleviated the activation of the CaMKII pathway. Pretreatment
      with m-3M3FBS attenuated the neuroprotective effect of NGR1; IICR was activated,
      activation of the ER stress and CaMKII pathway was increased, and more cells were
      injured. These results indicate that NGR1 may suppress activation of the PLC/IP3R
      pathway, subsequently inhibiting ER Ca2+ release, ER stress, and CaMKII and
      resulting in suppressed cell apoptosis.

PMID- 29176554
TI  - Membrane insertion of the BAX core, but not latch domain, drives apoptotic pore
      formation.
AB  - Despite intensive research effort, how the paradigmatic proapoptotic protein BAX
      forms lethal apoptotic pores at the mitochondrial outer membrane (MOM) remains
      incompletely understood. Here, we used biophysical tools and minimalist model
      systems to identify the specific regions in BAX driving apoptotic pore formation,
      and to gain more insight into underlying mechanisms. Fluorescence mapping
      revealed that fully active BAX adopts a BH3-in-groove dimeric conformation in MOM
      like membranes, with BAX alpha4-alpha5 helices belonging to its core domain
      inserting deeper into the membrane lipid bilayer than BAX alpha6-alpha8 helices
      belonging to its latch domain. In our reconstituted systems, antiapoptotic BCLXL
      formed canonical heterodimeric BH3-in-groove complexes with BAX, and blocked
      membrane insertion of BAX core alpha4-alpha5 helices, but not BAX latch alpha6
      alpha8 helices. Moreover, poly(ethylene glycol) (PEG) conjugation (PEGylation) at
      multiple individual sites along the BAX core, but not latch domain, potently
      inhibited BAX pore-forming activity. Additional combined computational and
      experimental evidence revealed that the BAX core alpha5 helix displays a bilayer
      destabilizing membrane interaction mode that is absent in BAX latch alpha6-alpha8
      helices. Based on this collective set of evidence, we propose that membrane
      insertion of the BAX core, but not latch domain, is critical for BAX apoptotic
      pore formation.

PMID- 29176555
TI  - Hydrogen mobility in the lightest reversible metal hydride, LiBeH3.
AB  - Lithium-beryllium metal hydrides, which are structurally related to their parent
      compound, BeH2, offer the highest hydrogen storage capacity by weight among the
      metal hydrides (15.93 wt. % of hydrogen for LiBeH3). Challenging synthesis
      protocols have precluded conclusive determination of their crystallographic
      structure to date, but here we analyze directly the hydrogen hopping mechanisms
      in BeH2 and LiBeH3 using quasielastic neutron scattering, which is especially
      sensitive to single-particle dynamics of hydrogen. We find that, unlike its
      parent compound BeH2, lithium-beryllium hydride LiBeH3 exhibits a sharp increase
      in hydrogen mobility above 265 K, so dramatic that it can be viewed as melting of
      hydrogen sublattice. We perform comparative analysis of hydrogen jump mechanisms
      observed in BeH2 and LiBeH3 over a broad temperature range. As microscopic
      diffusivity of hydrogen is directly related to its macroscopic kinetics, a
      transition in LiBeH3 so close to ambient temperature may offer a straightforward
      and effective mechanism to influence hydrogen uptake and release in this very
      lightweight hydrogen storage compound.

PMID- 29176556
TI  - Recognition of a likely two phased extinction at the K-Pg boundary in Antarctica.
AB  - The southernmost Cretaceous - Paleogene (K-Pg) outcrop exposure is the well
      studied exposure on Seymour Island, Antarctica. Deposition across the K-Pg
      boundary there is uninterrupted, and as a consequence the ammonite fossil record
      is commonly used to test statistical methods of evaluating mass extinctions to
      account for the incompleteness of the fossil record. Numerous detailed fossil
      data sets from Seymour Island, comprised dominantly of mollusks, have been
      published over the last 30 years, but in most cases have not received statistical
      treatment. Here a previously published statistical technique is modified,
      automated, and applied to all published macrofossil data sets available from
      Seymour Island. All data sets reveal likely evidence of two separate multi
      species extinctions, one synchronous with bolide impact evidence at the K-Pg
      boundary, and another 45 +/- 15 meters (~140-290 ky) below the boundary. The
      apparent earlier extinction primarily affects benthic mollusks, while the
      boundary extinction primarily affects ammonites. While there is no unique
      sedimentological change over the interval where the earlier extinction is
      identified, it is impossible to exclude the possibility that this pattern is
      stratigraphically controlled. The automation of this technique allows it to be
      applied easily to other large fossil data sets.

PMID- 29176557
TI  - Functional connectivity of the cortical network supporting statistical learning
      in musicians and non-musicians: an MEG study.
AB  - Statistical learning is a cognitive process of great importance for the detection
      and representation of environmental regularities. Complex cognitive processes
      such as statistical learning usually emerge as a result of the activation of
      widespread cortical areas functioning in dynamic networks. The present study
      investigated the cortical large-scale network supporting statistical learning of
      tone sequences in humans. The reorganization of this network related to musical
      expertise was assessed via a cross-sectional comparison of a group of musicians
      to a group of non-musicians. The cortical responses to a statistical learning
      paradigm incorporating an oddball approach were measured via
      Magnetoencephalographic (MEG) recordings. Large-scale connectivity of the
      cortical activity was calculated via a statistical comparison of the estimated
      transfer entropy in the sources' activity. Results revealed the functional
      architecture of the network supporting the processing of statistical learning,
      highlighting the prominent role of informational processing pathways that
      bilaterally connect superior temporal and intraparietal sources with the left
      IFG. Musical expertise is related to extensive reorganization of this network, as
      the group of musicians showed a network comprising of more widespread and
      distributed cortical areas as well as enhanced global efficiency and increased
      contribution of additional temporal and frontal sources in the information
      processing pathway.

PMID- 29176558
TI  - Intraspecific variation and plasticity in mitochondrial oxygen binding affinity
      as a response to environmental temperature.
AB  - Mitochondrial function has been suggested to underlie constraints on whole
      organism aerobic performance and associated hypoxia and thermal tolerance limits,
      but most studies have focused on measures of maximum mitochondrial capacity. Here
      we investigated whether variation in mitochondrial oxygen kinetics could
      contribute to local adaptation and plasticity in response to temperature using
      two subspecies of the Atlantic killifish (Fundulus heteroclitus) acclimated to a
      range of temperatures (5, 15, and 33  degrees C). The southern subspecies of F.
      heteroclitus, which has superior thermal and hypoxia tolerances compared to the
      northern subspecies, exhibited lower mitochondrial O2 P50 (higher O2 affinity).
      Acclimation to thermal extremes (5 or 33  degrees C) altered mitochondrial O2 P50
      in both subspecies consistent with the effects of thermal acclimation on whole
      organism thermal tolerance limits. We also examined differences between
      subspecies and thermal acclimation effects on whole-blood Hb O2-P50 to assess
      whether variation in oxygen delivery is involved in these responses. In contrast
      to the clear differences between subspecies in mitochondrial O2-P50 there were no
      differences in whole-blood Hb-O2 P50 between subspecies. Taken together these
      findings support a general role for mitochondrial oxygen kinetics in
      differentiating whole-organism aerobic performance and thus in influencing
      species responses to environmental change.

PMID- 29176559
TI  - ASXL1 frameshift mutations drive inferior outcomes in CMML without negative
      impact in MDS.

PMID- 29176560
TI  - An activity-dependent proximity ligation platform for spatially resolved
      quantification of active enzymes in single cells.
AB  - Integration of chemical probes into proteomic workflows enables the interrogation
      of protein activity, rather than abundance. Current methods limit the biological
      contexts that can be addressed due to sample homogenization, signal-averaging,
      and bias toward abundant proteins. Here we report a platform that integrates
      family-wide chemical probes with proximity-dependent oligonucleotide
      amplification and imaging to quantify enzyme activity in native contexts with
      high spatial resolution. Application of this method, activity-dependent proximity
      ligation (ADPL), to serine hydrolase and cysteine protease enzymes enables
      quantification of differential enzyme activity resulting from endogenous changes
      in localization and expression. In a competitive format, small-molecule target
      engagement with endogenous proteins in live cells can be quantified. Finally,
      retention of sample architecture enables interrogation of complex environments
      such as cellular co-culture and patient samples. ADPL should be amenable to
      diverse probe and protein families to detect active enzymes at scale and
      resolution out of reach with current methods.

PMID- 29176562
TI  - Understanding heat patterns produced by vehicular flows in urban areas.
AB  - Vehicular traffic has strong implication in the severity and degree of Urban Heat
      Island (UHI) effect in a city. It is crucial to map and monitor the spatio
      temporal heat patterns from vehicular traffic in a city. Data observed from
      traffic counting stations are readily available for mapping the traffic-related
      heat across the stations. However, macroscopic models utilizing traffic counting
      data to estimate dynamic directional vehicular flows are rarely established. Our
      work proposes a simple and robust cell-transmission-model to simulate all the
      possible cell-based origin-destination trajectories of vehicular flows over time,
      based on the traffic counting stations. Result shows that the heat patterns have
      notable daily and weekly periodical circulation/pattern, and volumes of heat vary
      significantly in different grid cells. The findings suggest that vehicular flows
      in some places are the dominating influential factor that make the UHI phenomenon
      more remarkable.

PMID- 29176561
TI  - HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid
      metabolism.
AB  - Clear cell renal cell carcinoma (ccRCC) is histologically defined by its lipid
      and glycogen-rich cytoplasmic deposits. Alterations in the VHL tumor suppressor
      stabilizing the hypoxia-inducible factors (HIFs) are the most prevalent molecular
      features of clear cell tumors. The significance of lipid deposition remains
      undefined. We describe the mechanism of lipid deposition in ccRCC by identifying
      the rate-limiting component of mitochondrial fatty acid transport, carnitine
      palmitoyltransferase 1A (CPT1A), as a direct HIF target gene. CPT1A is repressed
      by HIF1 and HIF2, reducing fatty acid transport into the mitochondria, and
      forcing fatty acids to lipid droplets for storage. Droplet formation occurs
      independent of lipid source, but only when CPT1A is repressed. Functionally,
      repression of CPT1A is critical for tumor formation, as elevated CPT1A expression
      limits tumor growth. In human tumors, CPT1A expression and activity are decreased
      versus normal kidney; and poor patient outcome associates with lower expression
      of CPT1A in tumors in TCGA. Together, our studies identify HIF control of fatty
      acid metabolism as essential for ccRCC tumorigenesis.

PMID- 29176563
TI  - Visualising the 3D microstructure of stained and native intervertebral discs
      using X-ray microtomography.
AB  - Intervertebral disc degeneration (IVDD) is linked to low back pain.
      Microstructural changes during degeneration have previously been imaged using 2D
      sectioning techniques and 3D methods which are limited to small specimens and
      prone to inducing artefacts from sample preparation. This study explores micro
      computed X-ray tomography (microCT) methods with the aim of resolving IVD 3D
      microstructure whilst minimising sample preparation artefacts. Low X-ray
      absorption contrast in non-mineralised tissue can be enhanced using staining and
      phase contrast techniques. A step-wise approach, including comparing three
      stains, was used to develop microCT for bovine tail IVD using laboratory and
      synchrotron sources. Staining successfully contrasted collagenous structures;
      however not all regions were stained and the procedure induced macroscopic
      structural changes. Phase contrast microCT of chemically fixed yet unstained
      samples resolved the nucleus pulposus, annulus fibrosus and constituent lamellae,
      and finer structures including collagen bundles and cross-bridges. Using the same
      imaging methods native tissue scans were of slightly lower contrast but free from
      sample processing artefacts. In the future these methods may be used to
      characterise structural remodelling in soft (non-calcified) tissues and to
      conduct in situ studies of native loaded tissues and constructs to characterise
      their 3D mechanical properties.

PMID- 29176564
TI  - Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicities and
      Transmissibilities in Mammals.
AB  - Since 2013, highly pathogenic avian influenza H5N6 viruses have emerged in
      poultry and caused sporadic infections in humans, increasing global concerns
      regarding their potential as human pandemic threats. Here, we characterized the
      receptor-binding specificities, pathogenicities and transmissibilities of three
      H5N6 viruses isolated from poultry in China. The surface genes hemagglutinin (HA)
      and neuraminidase (NA) were closely related to the human-originating strain
      A/Changsha/1/2014 (H5N6). Phylogenetic analyses showed that the HA genes were
      clustered in the 2.3.4.4 clade, and the NA genes were derived from H6N6 viruses.
      These H5N6 viruses bound both alpha-2,3-linked and alpha-2,6-linked sialic acid
      receptors, but they exhibited different pathogenicities in mice. In addition, one
      virus was fully infective and transmissible by direct contact in guinea pigs.
      These results highlight the importance of monitoring the continual adaptation of
      H5N6 viruses in poultry due to their potential threat to human health.

PMID- 29176565
TI  - New Early Cretaceous palaeomagnetic and geochronological results from the far
      western Lhasa terrane: Contributions to the Lhasa-Qiangtang collision.
AB  - To better constrain the Lhasa-Qiangtang collision, a combined palaeomagnetic and
      geochronological study of the far western Lhasa terrane was conducted on the
      Duoai Formation lava flows (~113-116 Ma), as well as on the Early Cretaceous
      Jiega Formation limestone. Following detailed rock magnetic, petrographical, and
      palaeomagnetic experiments, characteristic remanent magnetisation directions were
      successfully isolated from most samples using principal component analysis. The
      tilt-corrected direction groups yielded a palaeopole at 69.1 degrees N, 319.8
      degrees E with A95 = 4.8 degrees  (N = 19). A primary origin for the
      magnetisation is consistent with positive fold tests. Our results from the Early
      Cretaceous units, combined with published palaeomagnetic data obtained from
      Cretaceous strata from the Lhasa and western Qiangtang terranes, show that these
      two terranes had already collided by the Early Cretaceous, the Lhasa terrane had
      a relatively east-west alignment, and it remained at a relatively stable
      palaeolatitude during the entire Cretaceous. Comparing the Cretaceous
      palaeolatitude calculated for the western Lhasa terrane with those from Eurasia
      and Mongolia suggests a latitudinal convergence of ~1400 +/- 290 km and ~1800 +/-
      300 km, respectively, since the Early Cretaceous.

PMID- 29176566
TI  - Nanoscale investigation of enhanced electron field emission for silver ion
      implanted/post-annealed ultrananocrystalline diamond films.
AB  - Silver (Ag) ions are implanted in ultrananocrystalline diamond (UNCD) films to
      enhance the electron field emission (EFE) properties, resulting in low turn-on
      field of 8.5 V/MUm with high EFE current density of 6.2 mA/cm2 (at an applied
      field of 20.5 V/MUm). Detailed nanoscale investigation by atomic force microscopy
      based peak force-controlled tunneling atomic force microscopy (PF-TUNA) and ultra
      high vacuum scanning tunneling microscopy (STM) based current imaging tunneling
      spectroscopy (CITS) reveal that the UNCD grain boundaries are the preferred
      electron emission sites. The two scanning probe microscopic results supplement
      each other well. However, the PF-TUNA measurement is found to be better for
      explaining the local electron emission behavior than the STM-based CITS
      technique. The formation of Ag nanoparticles induced abundant sp2 nanographitic
      phases along the grain boundaries facilitate the easy transport of electrons and
      is believed to be a prime factor in enhancing the conductivity/EFE properties of
      UNCD films. The nanoscale understanding on the origin of electron emission sites
      in Ag-ion implanted/annealed UNCD films using the scanning probe microscopic
      techniques will certainly help in developing high-brightness electron sources for
      flat-panel displays applications.

PMID- 29176568
TI  - Low-temperature fabrication of an HfO2 passivation layer for amorphous indium
      gallium-zinc oxide thin film transistors using a solution process.
AB  - We report low-temperature solution processing of hafnium oxide (HfO2) passivation
      layers for amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors
      (TFTs). At 150  degrees C, the hafnium chloride (HfCl4) precursor readily
      hydrolyzed in deionized (DI) water and transformed into an HfO2 film. The
      fabricated HfO2 passivation layer prevented any interaction between the back
      surface of an a-IGZO TFT and ambient gas. Moreover, diffused Hf4+ in the back
      channel layer of the a-IGZO TFT reduced the oxygen vacancy, which is the origin
      of the electrical instability in a-IGZO TFTs. Consequently, the a-IGZO TFT with
      the HfO2 passivation layer exhibited improved stability, showing a decrease in
      the threshold voltage shift from 4.83 to 1.68 V under a positive bias stress test
      conducted over 10,000 s.

PMID- 29176567
TI  - Plasma cell survival in the absence of B cell memory.
AB  - Pre-existing serum antibodies play an important role in vaccine-mediated
      protection against infection but the underlying mechanisms of immune memory are
      unclear. Clinical studies indicate that antigen-specific antibody responses can
      be maintained for many years, leading to theories that
      reactivation/differentiation of memory B cells into plasma cells is required to
      sustain long-term antibody production. Here, we present a decade-long study in
      which we demonstrate site-specific survival of bone marrow-derived plasma cells
      and durable antibody responses to multiple virus and vaccine antigens in rhesus
      macaques for years after sustained memory B cell depletion. Moreover, BrdU+ cells
      with plasma cell morphology can be detected for 10 years after vaccination/BrdU
      administration, indicating that plasma cells may persist for a prolonged period
      of time in the absence of cell division. On the basis of these results, long
      lived plasma cells represent a key cell population responsible for long-term
      antibody production and serological memory.

PMID- 29176569
TI  - A novel peptidic inhibitor derived from Streptococcus cristatus ArcA attenuates
      virulence potential of Porphyromonas gingivalis.
AB  - Periodontitis is a global health problem and the 6th most common infectious
      disease worldwide. Porphyromonas gingivalis is considered a keystone pathogen in
      the disease and is capable of elevating the virulence potential of the
      periodontal microbial community. Strategies that interfere with P. gingivalis
      colonization and expression of virulence factor are therefore attractive
      approaches for preventing and treating periodontitis. We have previously reported
      that an 11-mer peptide (SAPP) derived from Streptococcus cristatus arginine
      deiminase (ArcA) was able to repress the expression and production of several
      well-known P. gingivalis virulence factors including fimbrial proteins and
      gingipains. Herein we expand and develop these studies to ascertain the impact of
      this peptide on phenotypic properties of P. gingivalis related to virulence
      potential. We found that growth rate was not altered by exposure of P. gingivalis
      to SAPP, while monospecies and heterotypic biofilm formation, and invasion of
      oral epithelial cells were inhibited. Additionally, SAPP was able to impinge the
      ability of P. gingivalis to dysregulate innate immunity by repressing gingipain
      associated degradation of interleukin-8 (IL8). Hence, SAPP has characteristics
      that could be exploited for the manipulation of P. gingivalis levels in oral
      communities and preventing realization of virulence potential.

PMID- 29176572
TI  - Emergent wave phenomena in coupled elastic bars: from extreme attenuation to
      realization of elastodynamic switches.
AB  - Metamaterials with acoustic and elastic band gaps are of great interest to
      scientists and engineers. Here, we introduce a novel mechanism for emergence of
      multiple band gaps with extreme attenuation by coupling continuous one
      dimensional elastic structures. We show that it is possible to develop extreme
      attenuation at several frequencies from coupling two homogenous bars of different
      elastodynamic properties even though each bar individually possesses no such
      gaps. Moreover, if each bar is a composite on its own, multiple resonant band
      gaps appear in the compound system which do not exist in either bar. We verify
      our results by conducting numerical simulations for the elastodynamic response
      and show that the resonant gaps are efficient in attenuating wave propagation.
      Furthermore, we show that by carefully tailoring the properties of the coupled
      bars we may construct elastodynamic signal choppers. These results open a new
      gate for designing Metamaterial with unique wave modulation properties.

PMID- 29176570
TI  - Population-scale organization of cerebellar granule neuron signaling during a
      visuomotor behavior.
AB  - Granule cells at the input layer of the cerebellum comprise over half the neurons
      in the human brain and are thought to be critical for learning. However, little
      is known about granule neuron signaling at the population scale during behavior.
      We used calcium imaging in awake zebrafish during optokinetic behavior to record
      transgenically identified granule neurons throughout a cerebellar population. A
      significant fraction of the population was responsive at any given time. In
      contrast to core precerebellar populations, granule neuron responses were
      relatively heterogeneous, with variation in the degree of rectification and the
      balance of positive versus negative changes in activity. Functional correlations
      were strongest for nearby cells, with weak spatial gradients in the degree of
      rectification and the average sign of response. These data open a new window upon
      cerebellar function and suggest granule layer signals represent elementary
      building blocks under-represented in core sensorimotor pathways, thereby enabling
      the construction of novel patterns of activity for learning.

PMID- 29176571
TI  - Health state dependent multiphoton induced autofluorescence in human 3D in vitro
      lung cancer model.
AB  - Lung diseases pose the highest risk of death and lung cancer is a top killer
      among cancers with a mortality rate up to 70% within 1 year after diagnosis. Such
      a fast escalation of this cancer development makes early diagnosis and treatment
      a highly challenging task, and currently there are no effective tools to diagnose
      the disease at an early stage. The ability to discriminate between healthy and
      tumorous tissue has made autofluorescence bronchoscopy a promising tool for
      detection of lung cancer; however, specificity of this method remains
      insufficiently low. Here, we perform autofluorescence imaging of human lung
      cancer invading a human functional airway using an in vitro model of Non Small
      Cell Lung Cancer which combines a reconstituted human airway epithelium, human
      lung fibroblasts and lung adenocarcinoma cell lines, OncoCilAirTM. By using two
      photon laser induced autofluorescence microscopy combined with spectrally
      resolved imaging, we found that OncoCilAirTM provides tissue's health dependent
      autofluorescence similar as observed in lung tissue in patients. Moreover, we
      found spectral and intensity heterogeneity of autofluorescence at the edges of
      tumors. This metabolic related heterogeneity demonstrates ability of tumor to
      influence its microenvironment. Together, our result shows that OncoCilAirTM is a
      promising model for lung cancer research.

PMID- 29176573
TI  - The Retinol Binding Protein Receptor 2 (Rbpr2) is required for Photoreceptor
      Outer Segment Morphogenesis and Visual Function in Zebrafish.
AB  - Vitamin A (all-trans retinol) plays critical roles in mammalian development and
      vision. Since vitamin A is food-derived, tissue-specific uptake and storage
      mechanism are needed. In the eye, uptake of RBP4-retinol is mediated by the
      receptor Stra6, whereas the receptor mediating RBP4 binding and retinol transport
      into the liver has just recently been discovered. Here we examined the role of
      zebrafish retinol binding protein receptor 2 (Rbpr2) for RBP4-retinol uptake in
      developing embryos, using eye development and vision as sensitive readouts. In
      cultured cells, Rbpr2 localized to membranes and promoted RBP4-retinol uptake. In
      larvae, Rbpr2 expression was detected in developing intestinal enterocytes and
      liver hepatocytes. Two rbpr2 mutant zebrafish lines, each resulting in Rbpr2
      deficiency, exhibit a small eye defect, and systemic malformations including
      hydrocephaly and cardiac edema, phenotypes associated with vitamin A deficiency.
      In the retina, Rbpr2 loss resulted in shorter photoreceptor outer segments,
      mislocalization and decrease in visual pigments, decreased expression of retinoic
      acid-responsive genes and photoreceptor cell loss, overall leading to a reduction
      of visual function. Together, these results demonstrate that Rbpr2-mediated RBP4
      retinol uptake in developing liver and intestine is necessary to provide
      sufficient substrate for ocular retinoid production required for photoreceptor
      cell maintenance and visual function.

PMID- 29176574
TI  - Habitat foraging niche of a High Arctic zooplanktivorous seabird in a changing
      environment.
AB  - Here, we model current and future distribution of a foraging Arctic endemic
      species, the little auk (Alle alle), a small zooplanktivorous Arctic seabird. We
      characterized environmental conditions [sea depth, sea surface temperature (SST),
      marginal sea ice zone (MIZ)] at foraging positions of GPS-tracked individuals
      from three breeding colonies in Svalbard: one located at the southern rim of the
      Arctic zone (hereafter 'boreo-Arctic') and two in the high-Arctic zone on
      Spitsbergen ('high-Arctic'). The birds from one 'high-Arctic' colony, influenced
      by cold Arctic water, foraged in the shallow shelf zone near the colony. The
      birds from remaining colonies foraged in a wider range of depths, in a higher SST
      zone ('boreo-Arctic') or in the productive but distant MIZ (second 'high-Arctic'
      colony). Given this flexible foraging behaviour, little auks may be temporarily
      resilient to moderate climate changes. However, our fuzzy logic models of future
      distribution under scenarios of 1  degrees C and 2  degrees C SST increase
      predict losses of suitable foraging habitat for the majority of little auk
      colonies studied. Over longer time scales negative consequences of global warming
      are inevitable. The actual response of little auks to future environmental
      conditions will depend on the range of their plasticity and pace of ecosystem
      changes.

PMID- 29176575
TI  - Phosphorylation of LAMP2A by p38 MAPK couples ER stress to chaperone-mediated
      autophagy.
AB  - Endoplasmic reticulum (ER) and lysosomes coordinate a network of key cellular
      processes including unfolded protein response (UPR) and autophagy in response to
      stress. How ER stress is signaled to lysosomes remains elusive. Here we find that
      ER disturbance activates chaperone-mediated autophagy (CMA). ER stressors lead to
      a PERK-dependent activation and recruitment of MKK4 to lysosomes, activating p38
      MAPK at lysosomes. Lysosomal p38 MAPK directly phosphorylates the CMA receptor
      LAMP2A at T211 and T213, which causes its membrane accumulation and active
      conformational change, activating CMA. Loss of ER stress-induced CMA activation
      sensitizes cells to ER stress-induced death. Neurotoxins associated with
      Parkinson's disease fully engages ER-p38 MAPK-CMA pathway in the mouse brain and
      uncoupling it results in a greater loss of SNc dopaminergic neurons. This work
      identifies the coupling of ER and CMA as a critical regulatory axis fundamental
      for physiological and pathological stress response.

PMID- 29176577
TI  - Disulfide loop cleavage of Legionella pneumophila PlaA boosts lysophospholipase A
      activity.
AB  - L. pneumophila, an important facultative intracellular bacterium, infects the
      human lung and environmental protozoa. At least fifteen phospholipases A (PLA)
      are encoded in its genome. Three of which, namely PlaA, PlaC, and PlaD, belong to
      the GDSL lipase family abundant in bacteria and higher plants. PlaA is a
      lysophospholipase A (LPLA) that destabilizes the phagosomal membrane in absence
      of a protective factor. PlaC shows PLA and glycerophospholipid: cholesterol
      acyltransferase (GCAT) activities which are activated by zinc metalloproteinase
      ProA via cleavage of a disulphide loop. In this work, we compared GDSL enzyme
      activities, their secretion, and activation of PlaA. We found that PlaA majorly
      contributed to LPLA, PlaC to PLA, and both substrate-dependently to GCAT
      activity. Western blotting revealed that PlaA and PlaC are type II-secreted and
      both processed by ProA. Interestingly, ProA steeply increased LPLA but diminished
      GCAT activity of PlaA. Deletion of 20 amino acids within a predicted disulfide
      loop of PlaA had the same effect. In summary, we propose a model by which ProA
      processes PlaA via disulfide loop cleavage leading to a steep increase in LPLA
      activity. Our results help to further characterize the L. pneumophila GDSL
      hydrolases, particularly PlaA, an enzyme acting in the Legionella-containing
      phagosome.

PMID- 29176578
TI  - A multi-country assessment of factors related to smallholder food security in
      varying rainfall conditions.
AB  - Given that smallholder farmers are frequently food insecure and rely
      significantly on rain-fed agriculture, it is critical to examine climate
      variability and food insecurity. We utilize data from smallholder farmer surveys
      from 12 countries with 30 years of rainfall data to examine how rainfall
      variability and household resources are correlated with food security. We find
      that on average, households that experienced a drier than average year are 3.81
      months food insecure, while households within a normal range of rainfall were
      3.67 months food insecure, and wetter than average households were 2.86 months
      food insecure. Reduced odds of food insecurity is associated with agricultural
      inputs, ownership of livestock, water use efficiency, financial services, and
      participation in a group. However, in drier than average households, financial
      services as compared to agricultural inputs and agroecological practices have a
      greater prevalence of reduced instances of food insecurity, while agricultural
      inputs are more common for reduced food insecurity in wetter than average
      households. Only the use of fertilizer consistently results in reduced odds of
      food insecurity across all households regardless of rainfall, demonstrating that
      one-size fits all approaches to food security interventions are likely
      ineffective, and place-specific interventions considering climatic factors are
      critically important.

PMID- 29176576
TI  - The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1.
AB  - Ubiquitin chains linked through lysine63 (K63) play a critical role in
      inflammatory signalling. Following ligand engagement of immune receptors, the
      RING E3 ligase TRAF6 builds K63-linked chains together with the heterodimeric E2
      enzyme Ubc13-Uev1A. Dimerisation of the TRAF6 RING domain is essential for the
      assembly of K63-linked ubiquitin chains. Here, we show that TRAF6 RING dimers
      form a catalytic complex where one RING interacts with a Ubc13~Ubiquitin
      conjugate, while the zinc finger 1 (ZF1) domain and linker-helix of the opposing
      monomer contact ubiquitin. The RING dimer interface is conserved across TRAFs and
      we also show that TRAF5-TRAF6 heterodimers form. Importantly, TRAF5 can provide
      ZF1, enabling ubiquitin transfer from a TRAF6-bound Ubc13 conjugate. Our study
      explains the dependence of activity on TRAF RING dimers, and suggests that both
      homo- and heterodimers mediated by TRAF RING domains have the capacity to
      synthesise ubiquitin chains.

PMID- 29176579
TI  - Regulation of mating type switching by the mating type genes and RME1 in Ogataea
      polymorpha.
AB  - Saccharomyces cerevisiae and its closely related yeasts undergo mating type
      switching by replacing DNA sequences at the active mating type locus (MAT) with
      one of two silent mating type cassettes. Recently, a novel mode of mating type
      switching was reported in methylotrophic yeast, including Ogataea polymorpha,
      which utilizes chromosomal recombination between inverted-repeat sequences
      flanking two MAT loci. The inversion is highly regulated and occurs only when two
      requirements are met: haploidy and nutritional starvation. However, links between
      this information and the mechanism associated with mating type switching are not
      understood. Here we investigated the roles of transcription factors involved in
      yeast sexual development, such as mating type genes and the conserved zinc finger
      protein Rme1. We found that co-presence of mating type a1 and alpha2 genes was
      sufficient to prevent mating type switching, suggesting that ploidy information
      resides solely in the mating type locus. Additionally, RME1 deletion resulted in
      a reduced rate of switching, and ectopic expression of O. polymorpha RME1
      overrode the requirement for starvation to induce MAT inversion. These results
      suggested that mating type switching in O. polymorpha is likely regulated by two
      distinct transcriptional programs that are linked to the ploidy and transmission
      of the starvation signal.

PMID- 29176580
TI  - Reduced loss aversion in pathological gambling and alcohol dependence is
      associated with differential alterations in amygdala and prefrontal functioning.
AB  - Diagnostic criteria for pathological gambling and alcohol dependence (AD) include
      repeated addictive behavior despite severe negative consequences. However, the
      concept of loss aversion (LA) as a facet of value-based decision making has not
      yet been used to directly compare these disorders. We hypothesized reduced LA in
      pathological gamblers (PG) and AD patients, correlation of LA with disorder
      severity, and reduced loss-related modulation of brain activity. 19 PG subjects,
      15 AD patients and 17 healthy controls (HC) engaged in a LA task in a functional
      magnetic resonance imaging setting. Imaging analyses focused on neural gain and
      loss sensitivity in the meso-cortico-limbic network of the brain. Both PG and AD
      subjects showed reduced LA. AD subjects showed altered loss-related modulation of
      activity in lateral prefrontal regions. PG subjects showed indication of altered
      amygdala-prefrontal functional connectivity. Although we observed reduced LA in
      both a behavioral addiction and a substance-related disorder our neural findings
      might challenge the notion of complete neuro-behavioral congruence of substance
      use disorders and behavioral addictions.

PMID- 29176581
TI  - Functional horizontal gene transfer from bacteria to eukaryotes.
AB  - Bacteria influence eukaryotic biology as parasitic, commensal or beneficial
      symbionts. Aside from these organismal interactions, bacteria have also been
      important sources of new genetic sequences through horizontal gene transfer (HGT)
      for eukaryotes. In this Review, we focus on gene transfers from bacteria to
      eukaryotes, discuss how horizontally transferred genes become functional and
      explore what functions are endowed upon a broad diversity of eukaryotes by genes
      derived from bacteria. We classify HGT events into two broad types: those that
      maintain pre-existing functions and those that provide the recipient with new
      functionality, including altered host nutrition, protection and adaptation to
      extreme environments.

PMID- 29176584
TI  - Parasite development: The missing link to Plasmodium gametocytogenesis.

PMID- 29176583
TI  - Bacterial Physiology: Touching base on bacterial surface sensing.

PMID- 29176582
TI  - Listeria monocytogenes: towards a complete picture of its physiology and
      pathogenesis.
AB  - Listeria monocytogenes is a food-borne pathogen responsible for a disease called
      listeriosis, which is potentially lethal in immunocompromised individuals. This
      bacterium, first used as a model to study cell-mediated immunity, has emerged
      over the past 20 years as a paradigm in infection biology, cell biology and
      fundamental microbiology. In this Review, we highlight recent advances in the
      understanding of human listeriosis and L. monocytogenes biology. We describe
      unsuspected modes of hijacking host cell biology, ranging from changes in
      organelle morphology to direct effects on host transcription via a new class of
      bacterial effectors called nucleomodulins. We then discuss advances in
      understanding infection in vivo, including the discovery of tissue-specific
      virulence factors and the 'arms race' among bacteria competing for a niche in the
      microbiota. Finally, we describe the complexity of bacterial regulation and
      physiology, incorporating new insights into the mechanisms of action of a series
      of riboregulators that are critical for efficient metabolic regulation,
      antibiotic resistance and interspecies competition.

PMID- 29176585
TI  - Archaea and the origin of eukaryotes.
AB  - This corrects the article DOI: 10.1038/nrmicro.2017.133.

PMID- 29176586
TI  - Environmental microbiology: Around the globe in 2.2 billion sequences.

PMID- 29176587
TI  - Insect-based diet, a promising nutritional source, modulates gut microbiota
      composition and SCFAs production in laying hens.
AB  - Insects could be potential nutritional sources both for humans and animals. Among
      these, Hermetia illucens, with good amount of chitin and proteins, represents a
      suitable diet replacement for laying hens. Little is known about insect diet
      effects on the microbial ecology of the gastrointestinal tract and bacterial
      metabolites production. In this study we investigated the effect of H. illucens
      larvae meal administration on cecal microbiota and short chain fatty acids
      (SCFAs) production in laying hens. 16S rDNA sequencing showed strong differences
      between cecal microbiota of soybean (SD) and insect diet (ID) groups both in type
      and relative abundance (unweighted and weighted beta diversity) of microbial
      species. In particular, Bacteroides plebeius, Elusimicrobium minutum,
      Alkaliphilus transvaalensis, Christensenella minuta, Vallitalea guaymasensis and
      Flavonifractor plautii represented the principal contributors of changes in gut
      microbiota composition of ID group (FDR p-values < 0.05). Of these, F. plautii,
      C. minuta and A. transvaalensis have the potential to degrade the chitin's insect
      meal and correlated with the observed high levels of gut SCFAs produced in ID
      group. These microorganisms may thus connect the chitin degradation with high
      SCFAs production. Our results suggest H. illucens as a potential prebiotic by
      well feeding gut microbiota.

PMID- 29176588
TI  - Alanine substitution in cellobiohydrolase provides new insights into substrate
      threading.
AB  - The glycoside hydrolase family 7 (GH7) member cellobiohydrolase (CBH) is a key
      enzyme that degrades crystalline cellulose, an important structural component of
      plant cell walls. As GH7 CBH is a major component in the enzyme mixture used to
      degrade biomass into fermentable glucose in biorefineries, enhancing its
      catalytic activity will significantly impact development in this field. GH7 CBH
      possesses a catalytic tunnel through which cellulose substrates are threaded and
      hydrolysed. Despite numerous studies dissecting this processive mechanism, the
      role of amino acid residues in the tunnel remains not fully understood. Herein,
      we examined the respective contributions of nine amino acid residues in the
      catalytic tunnel of GH7 CBH from Talaromyces cellulolyticus by substitution with
      alanine. As a result, N62A and K203A mutants were found to possess significantly
      higher cellulase activities than wild type. Molecular dynamics simulations showed
      that the N62 residue interacted strongly with the cellulose substrate, impeding
      threading, while the N62A mutant allowed cellulose to proceed more smoothly.
      Furthermore, the W63 residue was observed to facilitate twisting of the cellulose
      substrate in our simulations. This study helps elucidate cellulose threading and
      provides insight into biomass hydrolysis.

PMID- 29176589
TI  - Australia's influenza pandemic preparedness plans: an analysis.
AB  - We analysed Australian plans issued by the public sector and current at the time
      of the last human pandemic in 2009. They came from various levels of governance,
      and offered guidance in key domains. Using 13 established criteria, we rated 10
      plans (national, state, and territorial) for their usefulness to guide health and
      medical intervention, business continuity, and crisis communication, plus
      consideration of at-risk populations. The intended end-user of most plans was not
      clear, whether hospital manager, health worker, or policy maker. Scores ranged
      from 8 to 29 of a maximum possible of 39, with many inconsistencies between
      plans. Health system-related issues were better addressed than critical
      infrastructure and essential systems resilience. The needs of Indigenous
      populations and use of pneumococcal vaccination and antibiotics were rarely
      considered in plans. Pandemic response would be more effective if plans were
      standardised, clear, and were to include overlooked dimensions of a pandemic's
      impact as well as guidance for specified end-users.

PMID- 29176590
TI  - Nanocarrier-mediated delivery of alpha-mangostin for non-surgical castration of
      male animals.
AB  - The overpopulation of abandoned and stray companion animals has become a global
      crisis. The main purpose of this study was to develop a novel nanomedicine-based
      antifertility compound for non-surgical castration of male animals. Mangosteen
      (Garcinia mangostana L) pericarp extract has been shown to exhibit anti-fertility
      property. alpha-mangostin (AM)-loaded nanostructured lipid carrier (AM-NLC) was
      developed to improve male germ cell apoptosis. This study was conducted to
      investigate physicochemical properties of AM-NLC and determine the biological
      effects of AM-NLC on spermatogonia cells and testicular explants obtained from
      castrated testes. AM-NLC was produced through a hot homogenization technique. The
      negatively charged particle of AM-NLC was nano-sized with a narrow dispersity. AM
      NLC exhibited antiproliferative activity towards spermatogonium cells. It induced
      apoptosis in the cells. In addition, AM-NLC exhibited anti-inflammatory
      activities in lipopolysaccharide-activated macrophages. Abnormal anatomy of
      seminiferous tubule was noted following treatment of testicular explant with AM
      NLC. This nanomedicine-based sterilant would be a promising platform that may
      have utility in non-surgical castration of male animals by intra-testicular
      injection.

PMID- 29176591
TI  - Identifying metabolites by integrating metabolome databases with mass
      spectrometry cheminformatics.
AB  - Novel metabolites distinct from canonical pathways can be identified through the
      integration of three cheminformatics tools: BinVestigate, which queries the
      BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match
      unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a
      software tool for chromatographic deconvolution of high-resolution GC-MS or
      liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure
      elucidation program that uses a combination of 14 metabolome databases in
      addition to an enzyme promiscuity library. We showcase our workflow by annotating
      N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N
      methylalanine, and two propofol derivatives.

PMID- 29176592
TI  - A permanent window for the murine lung enables high-resolution imaging of cancer
      metastasis.
AB  - Stable, high-resolution intravital imaging of the lung has become possible
      through the utilization of vacuum-stabilized imaging windows. However, this
      technique is extremely invasive and limited to only hours in duration. Here we
      describe a minimally invasive, permanently implantable window for high-resolution
      intravital imaging of the murine lung that allows the mouse to survive surgery,
      recover from anesthesia, and breathe independently. Compared to vacuum-stabilized
      windows, this window produces the same high-quality images without vacuum-induced
      artifacts; it is also less invasive, which allows imaging of the same lung tissue
      over a period of weeks. We further adapt the technique of microcartography for
      reliable relocalization of the same cells longitudinally. Using commonly employed
      experimental, as well as more clinically relevant, spontaneous metastasis models,
      we visualize all stages of metastatic seeding, including: tumor cell arrival;
      extravasation; growth and progression to micrometastases; as well as tumor
      microenvironment of metastasis function, the hallmark of hematogenous
      dissemination of tumor cells.

PMID- 29176593
TI  - Shared genetic etiology of hypertension and stroke: evidence from bioinformatics
      analysis of genome-wide association studies.
AB  - Hypertension is the most significant modifiable risk factor for cerebrovascular
      disease. It has been estimated that about 54% of strokes worldwide can be
      attributed to hypertension. However, there has not been a systematic study
      assessing the shared genetic susceptibility to hypertension and stroke on a
      genome-wide level. In this study, SNPs associated with essential hypertension and
      stroke were collected from the NHGRI-EBI GWAS catalog, and genotype imputation
      were conducted using information from the 1000 Genomes Project. Subsequently, the
      SNPs and the mapped genes were compared between the two diseases. Finally,
      functional clustering was performed, and the enriched GO terms and KEGG pathways
      were further compared between hypertension and stroke. Comparison of these two
      groups of SNPs and genes identified only one shared SNP (rs3184504) and 11 shared
      genes. After genotype imputation, 129 shared SNPs and 16 shared genes were
      identified. These genes were significantly enriched in 10 GO terms, which were
      mainly involved in lipoprotein and triglyceride metabolism. Additionally, KEGG
      analysis identified one pathway, glycerolipid metabolism, as being significantly
      enriched in both diseases. The present study strongly suggests that the gene
      network regulating lipid metabolism and blood circulation is the major shared
      genetic etiology of hypertension and stroke.

PMID- 29176594
TI  - Subtype prediction of primary aldosteronism by combining aldosterone
      concentrations in the left adrenal vein and inferior vena cava: a multicenter
      collaborative study on adrenal venous sampling.
AB  - Subtype diagnosis of primary aldosteronism (PA) by adrenal vein sampling (AVS) is
      recommended as a mandatory step for indicating adrenal surgery. It is a
      technically demanding procedure, especially in the right adrenal vein. The aim of
      the study was to predict the subtype diagnosis in the absence of values from the
      right AVS. From the databases of nine centers (WAVES-J), 308 patients with PA who
      underwent successful AVS were studied. Based on the ipsilateral ratio (IR)
      (aldosterone/cortisol ratio of the left adrenal vein [A/Cleft AV] /
      aldosterone/cortisol ratio of the inferior vena cava [A/CIVC]), the patients were
      divided into two groups: the patients with IR >= 1.0 (n = 262) and those with IR
      < 1.0 (n = 46). In patients with IR > 1.0, the A/Cleft AV was significantly
      higher in patients with the left unilateral subtype than in patients with the
      bilateral subtype. Receiver operating characteristic (ROC) curve analysis
      revealed that an A/Cleft AV cutoff >68 showed 70.8% sensitivity and 93.5%
      specificity for the left unilateral subtype. On the other hand, in patients with
      IR < 1.0, the A/Cleft AV was significantly lower in patients with the right
      unilateral subtype. ROC analysis revealed that an A/Cleft AV cutoff <9 showed
      86.7% sensitivity and 75.0% specificity for the right unilateral subtype. Hence,
      the combination of the IR and A/C ratio in the left adrenal vein is useful for
      predicting the subtype. The present results provide important information for
      patients with PA in whom AVS was unsuccessful in the right adrenal vein.

PMID- 29176595
TI  - The presence of nonfunctioning adrenal incidentalomas increases arterial
      hypertension frequency and severity, and is associated with cortisol levels after
      dexamethasone suppression test.
AB  - There are limited data regarding the frequency of hypertension in nonfunctioning
      adrenal incidentaloma (NFAI). Our objectives were to investigate rates of
      hypertension and resistant hypertension in NFAI patients, and compare them to a
      control group without adrenal adenoma. We also aimed to evaluate the relationship
      between cortisol levels after 1 mg-dexamethasone suppression test (DST) and
      hypertension in NFAI patients. We selected 40 patients with NFAI and 40 control
      patients over the age of 18 without adrenal lesions on abdominal imaging. Data
      regarding hypertension, resistant hypertension, number, and type of
      antihypertensive drugs were collected from each subject. Blood samples for C
      reactive protein (CRP), plasma adrenocorticotropic hormone (ACTH) and
      dehydroepiandrosterone sulfate (DHEA-S) were also collected from the patients.
      Age, gender, race, smoking status, menopause status and BMI were comparable
      between patient and control groups. Patients with NFAI had a higher frequency of
      hypertension (72.5 vs. 47.5%; p = 0.04), resistant hypertension (37.9 vs. 11.1%;
      p = 0.04) and took three or more antihypertensive drugs (33.3 vs. 5.2%; p =
      0.002) when compared to the controls, respectively. NFAI patients with
      hypertension had higher mean cortisol levels after 1 mg-DST when compared to NFAI
      patients without hypertension (1.3 +/- 0.3 vs. 1.0 +/- 0.4; p = 0.03,
      respectively). We found a negative correlation between cortisol levels after 1 mg
      DST DHEA-S levels (r = -0.61; p < 0.001) and a positive correlation with CRP
      levels (r = 0.44; p = 0.02). In conclusion, NFAI patients presented a higher
      frequency of hypertension, resistant hypertension and used more antihypertensive
      medications when compared to the control group. We found an association between
      hypertension in NFAI patients and cortisol levels after 1 mg-DST.

PMID- 29176597
TI  - In vivo evidence that RBM5 is a tumour suppressor in the lung.
AB  - Cigarette smoking is undoubtedly a risk factor for lung cancer. Moreover, smokers
      with genetic mutations on chromosome 3p21.3, a region frequently deleted in
      cancer and notably in lung cancer, have a dramatically higher risk of aggressive
      lung cancer. The RNA binding motif 5 (RBM5) is one of the component genes in the
      3p21.3 tumour suppressor region. Studies using human cancer specimens and cell
      lines suggest a role for RBM5 as a tumour suppressor. Here we demonstrate, for
      the first time, an in vivo role for RBM5 as a tumour suppressor in the mouse
      lung. We generated Rbm5 loss-of-function mice and exposed them to a tobacco
      carcinogen NNK. Upon exposure to NNK, Rbm5 loss-of-function mice developed lung
      cancer at similar rates to wild type mice. As tumourigenesis progressed, however,
      reduced Rbm5 expression lead to significantly more aggressive lung cancer i.e.
      increased adenocarcinoma nodule numbers and tumour size. Our data provide in vivo
      evidence that reduced RBM5 function, as occurs in a large number of patients,
      coupled with exposure to tobacco carcinogens is a risk factor for an aggressive
      lung cancer phenotype. These data suggest that RBM5 loss-of-function likely
      underpins at least part of the pro-tumourigenic consequences of 3p21.3 deletion
      in humans.

PMID- 29176598
TI  - Population pharmacokinetics of remifentanil in critically ill patients receiving
      extracorporeal membrane oxygenation.
AB  - Extracorporeal membrane oxygenation (ECMO) is associated with pharmacokinetic
      (PK) changes of drugs. It presents considerable challenges to providing optimal
      dosing regimens for patients receiving ECMO. We aimed to describe the population
      PK of remifentanil in critically ill adult patients receiving venoartrial
      extracorporeal membrane oxygenation (VA-ECMO) and to identify determinants
      associated with altered remifentanil concentrations. The population PK model of
      remifentanil was developed using nonlinear mixed effects modelling (NONMEM).
      Fifteen adult patients who received a continuous infusion of remifentanil during
      VA-ECMO participated in the study. The PK of remifentanil was best described by a
      one-compartment model with additive and proportional residual errors.
      Remifentanil concentrations were affected by sex and ECMO pump speed. The final
      PK model included the effect of sex and ECMO pump speed on clearance is developed
      as followed: clearance (L/h) = 366 * 0.502sex * (ECMO pump speed/2350)2.04 and
      volume (L) = 41. Remifentanil volume and clearance were increased in adult
      patients on VA-ECMO compared with previously reported patients not on ECMO. We
      suggest that clinicians should consider an increased remifentanil dosing to
      achieve the desired level of sedation and provide a dosing regimen according to
      sex and ECMO pump speed.

PMID- 29176596
TI  - Quenching protein dynamics interferes with HIV capsid maturation.
AB  - Maturation of HIV-1 particles encompasses a complex morphological transformation
      of Gag via an orchestrated series of proteolytic cleavage events. A longstanding
      question concerns the structure of the C-terminal region of CA and the peptide
      SP1 (CA-SP1), which represents an intermediate during maturation of the HIV-1
      virus. By integrating NMR, cryo-EM, and molecular dynamics simulations, we show
      that in CA-SP1 tubes assembled in vitro, which represent the features of an
      intermediate assembly state during maturation, the SP1 peptide exists in a
      dynamic helix-coil equilibrium, and that the addition of the maturation
      inhibitors Bevirimat and DFH-055 causes stabilization of a helical form of SP1.
      Moreover, the maturation-arresting SP1 mutation T8I also induces helical
      structure in SP1 and further global dynamical and conformational changes in CA.
      Overall, our results show that dynamics of CA and SP1 are critical for orderly
      HIV-1 maturation and that small molecules can inhibit maturation by perturbing
      molecular motions.

PMID- 29176599
TI  - Benchmarking organic mixed conductors for transistors.
AB  - Organic mixed conductors have garnered significant attention in applications from
      bioelectronics to energy storage/generation. Their implementation in organic
      transistors has led to enhanced biosensing, neuromorphic function, and
      specialized circuits. While a narrow class of conducting polymers continues to
      excel in these new applications, materials design efforts have accelerated as
      researchers target new functionality, processability, and improved
      performance/stability. Materials for organic electrochemical transistors (OECTs)
      require both efficient electronic transport and facile ion injection in order to
      sustain high capacity. In this work, we show that the product of the electronic
      mobility and volumetric charge storage capacity (uC*) is the materials/system
      figure of merit; we use this framework to benchmark and compare the steady-state
      OECT performance of ten previously reported materials. This product can be
      independently verified and decoupled to guide materials design and processing.
      OECTs can therefore be used as a tool for understanding and designing new organic
      mixed conductors.

PMID- 29176600
TI  - Cleavage of poly(A)-binding protein by duck hepatitis A virus 3C protease.
AB  - During viral infections, some viruses subvert the host proteins to promote the
      translation or RNA replication with their protease-mediated cleavage. Poly (A)
      binding protein (PABP) is a target for several RNA viruses; however, the impact
      of duck hepatitis A virus (DHAV) on PABP remains unknown. In this study, we
      demonstrated for the first time that DHAV infection stimulates a decrease in
      endogenous PABP and generates two cleavage fragments. On the basis of in vitro
      cleavage assays, an accumulation of PABP cleavage fragments was detected in duck
      embryo fibroblast (DEF) cell extracts incubated with functional DHAV 3C protease.
      In addition, DHAV 3C protease was sufficient for the cleavage of recombinant PABP
      without the assistance of other eukaryotic cellular cofactors. Furthermore, using
      site-directed mutagenesis, our data demonstrated a 3C protease cleavage site
      located between Q367 and G368 in duck PABP. Moreover, the knockdown of PABP
      inhibited the production of viral RNA, and the C-terminal domain of PABP caused a
      reduction in viral replication compared to the N-terminal domain. Taken together,
      these findings suggested that DHAV 3C protease mediates the cleavage of PABP,
      which may be a strategy to manipulate viral replication.

PMID- 29176601
TI  - Emergence of tick-borne diseases at northern latitudes in Europe: a comparative
      approach.
AB  - The factors that drive the emergence of vector-borne diseases are difficult to
      identify due to the complexity of the pathogen-vector-host triad. We used a novel
      comparative approach to analyse four long-term datasets (1995-2015) on the
      incidence of tick-borne diseases in humans and livestock (Lyme disease,
      anaplasmosis and babesiosis) over a geographic area that covered the whole of
      Norway. This approach allowed us to separate general (shared vector) and specific
      (pathogen reservoir host) limiting factors of tick-borne diseases, as well as the
      role of exposure (shared and non-shared pathogens in different hosts). We found
      broadly similar patterns of emergence across the four tick-borne diseases.
      Following initial increases during the first decade of the time series, the
      numbers of cases peaked at slightly different years and then stabilized or
      declined in the most recent years. Contrasting spatial patterns of disease
      incidence were consistent with exposure to ticks being an important factor
      influencing disease incidence in livestock. Uncertainty regarding the reservoir
      host(s) of the pathogens causing anaplasmosis and babesiosis prevented a firm
      conclusion regarding the role of the reservoir host-pathogen distribution. Our
      study shows that the emergence of tick-borne diseases at northern latitudes is
      linked to the shared tick vector and that variation in host-pathogen distribution
      and exposure causes considerable variation in emergence.

PMID- 29176602
TI  - Identification of DmTTLL5 as a Major Tubulin Glutamylase in the Drosophila
      Nervous System.
AB  - Microtubules (MTs) play crucial roles during neuronal life. They are formed by
      heterodimers of alpha and beta-tubulins, which are subjected to several post
      translational modifications (PTMs). Amongst them, glutamylation consists in the
      reversible addition of a variable number of glutamate residues to the C-terminal
      tails of tubulins. Glutamylation is the most abundant MT PTM in the mammalian
      adult brain, suggesting that it plays an important role in the nervous system
      (NS). Here, we show that the previously uncharacterized CG31108 gene encodes an
      alpha-tubulin glutamylase acting in the Drosophila NS. We show that this
      glutamylase, which we named DmTTLL5, initiates MT glutamylation specifically on
      alpha-tubulin, which are the only glutamylated tubulin in the Drosophila brain.
      In DmTTLL5 mutants, MT glutamylation was not detected in the NS, allowing for
      determining its potential function. DmTTLL5 mutants are viable and we did not
      find any defect in vesicular axonal transport, synapse morphology and larval
      locomotion. Moreover, DmTTLL5 mutant flies display normal negative geotaxis
      behavior and their lifespan is not altered. Thus, our work identifies DmTTLL5 as
      the major enzyme responsible for initiating neuronal MT glutamylation
      specifically on alpha-tubulin and we show that the absence of MT glutamylation is
      not detrimental for Drosophila NS function.

PMID- 29176603
TI  - The association between visual function and retinal structure in chronic central
      serous chorioretinopathy.
AB  - The purpose of the current study was to investigate the association between
      visual function and retinal structure in central serous chorioretinopathy (CSC).
      In 22 eyes of 22 chronic CSC patients with serous retinal detachment at the
      macula, retinal sensitivity was measured using MP3 microperimetry (NIDEK, Japan)
      and mean sensitivity within two degrees (MS2), four degrees (MS4) and six degrees
      (MS6), as well as foveal sensitivity (MS0), were calculated. Retinal structure
      was measured using optical coherence tomography (OCT, Spectralis, Heidelberg).
      The relationship between visual function (LogMAR best-corrected visual acuity
      [LogMAR VA] and MS0, MS2, MS4, MS6) and serous retinal detachment height at the
      fovea (SRDH), central retinal thickness (CRT), macular volume (MV) and central
      choroidal thickness (CCT) was investigated. There were significant negative
      correlations between LogMAR VA and MS0 (p = 0.016), MS2 (p = 0.049). No
      significant relationship was observed between LogMAR VA and SRDH (p = 0.97)
      although there was a significant negative correlation between SRDH and MS2 (p =
      0.028), MS4 (p = 0.049), MS6 (p = 0.023). In conclusion, in CSC, serous retinal
      detachment was significantly correlated with retinal sensitivity measured with
      MP3, but not with LogMAR VA.

PMID- 29176604
TI  - A comparison of micro-CT and histomorphometry for evaluation of osseointegration
      of PEO-coated titanium implants in a rat model.
AB  - The aim of the present study was to determine the correlation between bone volume
      density (BV/TV) around a titanium implant determined by micro-computed tomography
      (micro-CT) and bone area density (BA/TA) measurements obtained using
      histomorphometry. An intramedullary rat femur implant model was evaluated to
      compare raw titanium implants with plasma electrolytic oxidation (PEO)-coated
      titanium implants. Titanium and PEO-treated titanium pins were inserted into rat
      femurs under general anesthesia. The animals were sacrificed and femurs harvested
      at 0, 2, 4 and 6 weeks, and subsequently, histomorphometry and micro-CT were
      performed. BV/TV and BA/TA values were strongly and positively correlated at all
      time points and locations (with all correlation coefficients being >0.8 and with
      P < 0.001). BV/TV and BA/TA were significantly higher proximal to the growth
      plate than distal to the growth plate, with estimated differences of 14.10% (P <
      0.001) and 11.95% (P < 0.001), respectively. BV/TV and BA/TA were significantly
      higher on the PEO-coated surface than on the raw titanium surface, with estimated
      differences of 3.20% (P = 0.044) and 4.10% (P = 0.018), respectively. Therefore,
      quantitative micro-CT analysis of BV/TV is correlated with BA/TA determined by
      histomorphometry when artifacts around titanium implants are minimized by a
      region of interest modification.

PMID- 29176605
TI  - Mechanistic insight to ROS and Apoptosis regulated cytotoxicity inferred by Green
      synthesized CuO nanoparticles from Calotropis gigantea to Embryonic Zebrafish.
AB  - With the rapid development of nanotechnology, much has been anticipated with
      copper oxide nanoparticles (CuO NP) due to their extensive industrial and
      commercial application. However, it has raised concern over the environmental
      safety and human health effects. In this study, CuO nanoparticles were
      synthesized using the green method with floral extract of Calotropis gigantea and
      characterized by standard physiochemical techniques like DLS, Zeta potential
      determination, UV- Visible Spectroscopy, XRD, FTIR, FESEM, and TEM. Mechanistic
      cytotoxicity studies were performed using experimental and computational assays
      including morphological analysis, hatching, and viability rate analysis along
      with ROS and apoptosis analysis. Physiochemical characterization of CuO NP
      determined the size and zeta potential of synthesized nanoparticles to be 30 +/-
      09 nm to 40 +/- 2 nm and -38 mV +/- 12 mV respectively. Cytotoxicity evaluation
      with Zebrafish revealed malfunctioned organ development with differential
      viability and hatching rate at 48 hpf and 72 hpf with LC50 of 175 +/- 10 mg/l.
      Computational analysis depicted the influential role of CuO nanoparticles on
      zebrafish embryo's he1a, sod1 and p53 functional expression through hydrophobic
      and hydrogen bond interaction with amino acid residues. Study demonstrated
      valuable information of cytotoxic impact which can be influential in further
      studies of their eco-toxicological effects.

PMID- 29176606
TI  - Synthetic biology: Multiplex genome engineering in eukaryotes.

PMID- 29176607
TI  - Gate-tunable large magnetoresistance in an all-semiconductor spin valve device.
AB  - A large spin-dependent and electric field-tunable magnetoresistance of a two
      dimensional electron system is a key ingredient for the realization of many novel
      concepts for spin-based electronic devices. The low magnetoresistance observed
      during the last few decades in devices with lateral semiconducting transport
      channels between ferromagnetic source and drain contacts has been the main
      obstacle for realizing spin field effect transistor proposals. Here, we show both
      a large two-terminal magnetoresistance in a lateral spin valve device with a two
      dimensional channel, with up to 80% resistance change, and tunability of the
      magnetoresistance by an electric gate. The enhanced magnetoresistance is due to
      finite electric field effects at the contact interface, which boost spin-to
      charge conversion. The gating scheme that we use is based on switching between
      uni- and bidirectional spin diffusion, without resorting to spin-orbit coupling.
      Therefore, it can also be employed in materials with low spin-orbit coupling.

PMID- 29176608
TI  - Computational derivation of a molecular framework for hair follicle biology from
      disease genes.
AB  - Knowledge about genetic drivers of disease increases the efficiency of
      interpreting patient DNA sequence and helps to identify and prioritize biological
      points of intervention. Discoveries of genes with single mutations exerting
      substantial phenotypic impact reliably provide new biological insight, although
      such approaches tend to generate knowledge that is disjointed from the complexity
      of biological systems governed by elaborate networks. Here we sought to
      facilitate diagnostic sequencing for hair disorders and assess the underlying
      biology by compiling an archive of 684 genes discovered in studies of monogenic
      disorders and identifying molecular annotations enriched by them. To demonstrate
      utility for this dataset, we performed two data driven analyses. First, we
      extracted and analyzed data implicating enriched signaling pathways and
      identified previously unrecognized contributions from Hippo signaling. Second, we
      performed hierarchical clustering on the entire dataset to investigate the
      underlying causal structure of hair disorders. We identified 35 gene clusters
      representing genetically derived biological modules that provide a foundation for
      the development of a new disease taxonomy grounded in biology, rather than
      clinical presentations alone. This Resource will be useful for diagnostic
      sequencing in patients with diseases affecting the hair follicle, improved
      characterization of hair follicle biology, and methods development in precision
      medicine.

PMID- 29176609
TI  - Very high density EEG elucidates spatiotemporal aspects of early visual
      processing.
AB  - Standard human EEG systems based on spatial Nyquist estimates suggest that 20-30
      mm electrode spacing suffices to capture neural signals on the scalp, but recent
      studies posit that increasing sensor density can provide higher resolution neural
      information. Here, we compared "super-Nyquist" density EEG ("SND") with Nyquist
      density ("ND") arrays for assessing the spatiotemporal aspects of early visual
      processing. EEG was measured from 128 electrodes arranged over occipitotemporal
      brain regions (14 mm spacing) while participants viewed flickering checkerboard
      stimuli. Analyses compared SND with ND-equivalent subsets of the same electrodes.
      Frequency-tagged stimuli were classified more accurately with SND than ND arrays
      in both the time and the frequency domains. Representational similarity analysis
      revealed that a computational model of V1 correlated more highly with the SND
      than the ND array. Overall, SND EEG captured more neural information from visual
      cortex, arguing for increased development of this approach in basic and
      translational neuroscience.

PMID- 29176611
TI  - Dependence of the sliding distance of a one-dimensional atom chain on initial
      velocity.
AB  - In our daily lives, a body with a high initial velocity sliding freely on a rough
      surface moves a longer distance than that with a low initial velocity. However,
      such a phenomenon may not occur in the microscopic world. The dynamical behavior
      of a one-dimensional atom chain (1DAC) sliding on a substrate is investigated in
      this study by using a modified Frenkel-Kontorova model, in which the vibration of
      atoms on the substrate is considered. The dependence of sliding distance on
      initial velocity is examined. Result shows that although sliding distance is
      proportional to the initial value for most velocities, such a linear relation
      does not exist in some special velocities. This phenomenon is explained by a
      theoretical analysis of phonon excitation. The physical process is divided into
      three stages. The first stage is a superlubric sliding process with small
      amplitude of the vibrication of the atoms. The single-mode phonon is excited in
      the second stage. In the third stage, the system exhibits instability because of
      multiple-mode phonon excitations. In addition, the dependence of the coupling
      strength between 1DAC and the substrate is investigated. The findings are helpful
      in understanding the energy dissipation mechanism of friction.

PMID- 29176610
TI  - Reconstitution of the complete pathway of ITS2 processing at the pre-ribosome.
AB  - Removal of internal transcribed spacer 2 (ITS2) from pre-ribosomal RNA is
      essential to make functional ribosomes. This complicated processing reaction
      begins with a single endonucleolytic cleavage followed by exonucleolytic trimming
      at both new cleavage sites to generate mature 5.8S and 25S rRNA. We reconstituted
      the 7S->5.8S processing branch within ITS2 using purified exosome and its nuclear
      cofactors. We find that both Rrp44's ribonuclease activities are required for
      initial RNA shortening followed by hand over to the exonuclease Rrp6. During the
      in vitro reaction, ITS2-associated factors dissociate and the underlying 'foot'
      structure of the pre-60S particle is dismantled. 7S pre-rRNA processing is
      independent of 5S RNP rotation, but 26S->25S trimming is a precondition for
      subsequent 7S->5.8S processing. To complete the in vitro assay, we reconstituted
      the entire cycle of ITS2 removal with a total of 18 purified factors, catalysed
      by the integrated activities of the two participating RNA-processing machines,
      the Las1 complex and nuclear exosome.

PMID- 29176612
TI  - Biased and unbiased perceptual decision-making on vocal emotions.
AB  - Perceptual decision-making on emotions involves gathering sensory information
      about the affective state of another person and forming a decision on the
      likelihood of a particular state. These perceptual decisions can be of varying
      complexity as determined by different contexts. We used functional magnetic
      resonance imaging and a region of interest approach to investigate the brain
      activation and functional connectivity behind two forms of perceptual decision
      making. More complex unbiased decisions on affective voices recruited an extended
      bilateral network consisting of the posterior inferior frontal cortex, the
      orbitofrontal cortex, the amygdala, and voice-sensitive areas in the auditory
      cortex. Less complex biased decisions on affective voices distinctly recruited
      the right mid inferior frontal cortex, pointing to a functional distinction in
      this region following decisional requirements. Furthermore, task-induced neural
      connectivity revealed stronger connections between these frontal, auditory, and
      limbic regions during unbiased relative to biased decision-making on affective
      voices. Together, the data shows that different types of perceptual decision
      making on auditory emotions have distinct patterns of activations and functional
      coupling that follow the decisional strategies and cognitive mechanisms involved
      during these perceptual decisions.

PMID- 29176613
TI  - Global landscape of cell envelope protein complexes in Escherichia coli.
AB  - Bacterial cell envelope protein (CEP) complexes mediate a range of processes,
      including membrane assembly, antibiotic resistance and metabolic coordination.
      However, only limited characterization of relevant macromolecules has been
      reported to date. Here we present a proteomic survey of 1,347 CEPs encompassing
      90% inner- and outer-membrane and periplasmic proteins of Escherichia coli. After
      extraction with non-denaturing detergents, we affinity-purified 785 endogenously
      tagged CEPs and identified stably associated polypeptides by precision mass
      spectrometry. The resulting high-quality physical interaction network, comprising
      77% of targeted CEPs, revealed many previously uncharacterized heteromeric
      complexes. We found that the secretion of autotransporters requires translocation
      and the assembly module TamB to nucleate proper folding from periplasm to cell
      surface through a cooperative mechanism involving the beta-barrel assembly
      machinery. We also establish that an ABC transporter of unknown function, YadH,
      together with the Mla system preserves outer membrane lipid asymmetry. This E.
      coli CEP 'interactome' provides insights into the functional landscape governing
      CE systems essential to bacterial growth, metabolism and drug resistance.

PMID- 29176614
TI  - Inhibition of 53BP1 favors homology-dependent DNA repair and increases CRISPR
      Cas9 genome-editing efficiency.
AB  - Programmable nucleases, such as Cas9, are used for precise genome editing by
      homology-dependent repair (HDR). However, HDR efficiency is constrained by
      competition from other double-strand break (DSB) repair pathways, including non
      homologous end-joining (NHEJ). We report the discovery of a genetically encoded
      inhibitor of 53BP1 that increases the efficiency of HDR-dependent genome editing
      in human and mouse cells. 53BP1 is a key regulator of DSB repair pathway choice
      in eukaryotic cells and functions to favor NHEJ over HDR by suppressing end
      resection, which is the rate-limiting step in the initiation of HDR. We screened
      an existing combinatorial library of engineered ubiquitin variants for inhibitors
      of 53BP1. Expression of one variant, named i53 (inhibitor of 53BP1), in human and
      mouse cells, blocked accumulation of 53BP1 at sites of DNA damage and improved
      gene targeting and chromosomal gene conversion with either double-stranded DNA or
      single-stranded oligonucleotide donors by up to 5.6-fold. Inhibition of 53BP1 is
      a robust method to increase efficiency of HDR-based precise genome editing.

PMID- 29176615
TI  - Design and applications of a clamp for Green Fluorescent Protein with picomolar
      affinity.
AB  - Green fluorescent protein (GFP) fusions are pervasively used to study structures
      and processes. Specific GFP-binders are thus of great utility for detection,
      immobilization or manipulation of GFP-fused molecules. We determined structures
      of two designed ankyrin repeat proteins (DARPins), complexed with GFP, which
      revealed different but overlapping epitopes. Here we show a structure-guided
      design strategy that, by truncation and computational reengineering, led to a
      stable construct where both can bind simultaneously: by linkage of the two
      binders, fusion constructs were obtained that "wrap around" GFP, have very high
      affinities of about 10-30 pM, and extremely slow off-rates. They can be natively
      produced in E. coli in very large amounts, and show excellent biophysical
      properties. Their very high stability and affinity, facile site-directed
      functionalization at introduced unique lysines or cysteines facilitate many
      applications. As examples, we present them as tight yet reversible immobilization
      reagents for surface plasmon resonance, as fluorescently labelled monomeric
      detection reagents in flow cytometry, as pull-down ligands to selectively enrich
      GFP fusion proteins from cell extracts, and as affinity column ligands for
      inexpensive large-scale protein purification. We have thus described a general
      design strategy to create a "clamp" from two different high-affinity repeat
      proteins, even if their epitopes overlap.

PMID- 29176616
TI  - Current data on extremities chronic osteomyelitis in southwest China:
      epidemiology, microbiology and therapeutic consequences.
AB  - The current study was designed to explore the epidemiology of extremities chronic
      osteomyelitis, its prognosis and the complications of the treatment methods being
      used in southwest China. The data from osteomyelitis patients treated at the
      Department of Orthopaedics, Southwest Hospital, China between May 2011 and
      September 2016 were collected and analysed. The study comprised 503 admitted
      patients, of which 416 males and 87 were females, with an average age of 40.15 +/
      5.64 years. Approximately 356 cases were followed for more than 18 months; the
      average bone union time was 6.24 +/- 0.76 months in 94.1% (335) patients, and
      infections were almost controlled in 93.8% patients. The rate of infection
      control with the induced membrane technique was higher than with the I-stage free
      bone graft. Iliac infection was the main complication of the induced membrane
      technique, and impaired joint activity was the main complication of I-stage free
      bone grafts. In southwest China, the incidence of haematogenous osteomyelitis,
      caused mainly by Staphylococcus aureus, remains very high. The speed of bone
      defect repair and the rate of infection control with the induced membrane
      technique were superior to those of I-stage free bone grafts. Internal fixation
      should be given priority because it offers reduced complications with no increase
      in the recurrence of infection.

PMID- 29176617
TI  - Thae use of microfluic spinning fiber as an ophthalmology suture showing the good
      anastomotic strength control.
AB  - Adjusting the mechanical strength of a biomaterial to suit its intended
      application is very important for realizing beneficial outcomes. Microfluidic
      spinning fiber have been attracting attention recently due to their various
      advantages, but their mechanical strength has unfortunately not been a subject of
      concentrated research, and this lack of research has severely limited their
      applications. In the current work, we showed the mechanical properties of
      microfibers can be tuned easily and provided a mathematical explanation for how
      the microfluidic spinning method intrinsically controls the mechanical properties
      of a microfluidic spinning fiber. But we were also able to adjust the mechanical
      properties of such fibers in various other ways, including by using biomolecules
      to coat the fiber or mixing the biomolecules with the primary component of the
      fiber and by using a customized twisting machine to change the number of single
      microfiber strands forming the fiber. We used the bundle fiber as an
      ophthalmology suture that resulted in a porcine eye with a smoother post
      operative surface than did a nylon suture. The results showed the possibility
      that the proposed method can solve current problems of the microfibers in
      practical applications, and can thus extend the range of applications of these
      microfibers.

PMID- 29176618
TI  - Degradation Mechanism of Ag Nanorods for Surface Enhanced Raman Spectroscopy.
AB  - This paper reports a degradation mechanism of silver (Ag) nanorods that are used
      as substrates for surface enhanced Raman spectroscopy (SERS). The attachment of
      sulfur and hydrocarbons to the surfaces of Ag nanorods is observed when they are
      stored in ambient over four months. This attachment is observed to correlate with
      ~20% decrease in SERS signal. The attachment, and thereby the signal degradation,
      takes three weeks to complete, and remains stable after the initial decay over
      the rest of the four month test period. While this degradation mechanism is a
      limitation to the gross enhancement, the ensuing stability beyond three weeks is
      encouraging.

PMID- 29176621
TI  - Wind-generated Electricity in China: Decreasing Potential, Inter-annual
      Variability and Association with Changing Climate.
AB  - China hosts the world's largest market for wind-generated electricity. The
      financial return and carbon reduction benefits from wind power are sensitive to
      changing wind resources. Wind data derived from an assimilated meteorological
      database are used here to estimate what the wind generated electricity in China
      would have been on an hourly basis over the period 1979 to 2015 at a geographical
      resolution of approximately 50 km * 50 km. The analysis indicates a secular
      decrease in generating potential over this interval, with the largest declines
      observed for western Inner Mongolia (15 +/- 7%) and the northern part of Gansu
      (17 +/- 8%), two leading wind investment areas. The decrease is associated with
      long-term warming in the vicinity of the Siberian High (SH), correlated also with
      the observed secular increase in global average surface temperatures. The long
      term trend is modulated by variability relating to the Pacific Decadal
      Oscillation (PDO) and the Arctic Oscillation (AO). A linear regression model
      incorporating indices for the PDO and AO, as well as the declining trend, can
      account for the interannual variability of wind power, suggesting that advances
      in long-term forecasting could be exploited to markedly improve management of
      future energy systems.

PMID- 29176619
TI  - STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in
      dendritic cells.
AB  - Antigen cross-presentation by dendritic cells (DC) stimulates cytotoxic T cell
      activation to promote immunity to intracellular pathogens, viruses and cancer.
      Phagocytosed antigens generate potent T cell responses, but the signalling and
      trafficking pathways regulating their cross-presentation are unclear. Here, we
      show that ablation of the store-operated-Ca2+-entry regulator STIM1 in mouse
      myeloid cells impairs cross-presentation and DC migration in vivo and in vitro.
      Stim1 ablation reduces Ca2+ signals, cross-presentation, and chemotaxis in mouse
      bone-marrow-derived DCs without altering cell differentiation, maturation or
      phagocytic capacity. Phagosomal pH homoeostasis and ROS production are unaffected
      by STIM1 deficiency, but phagosomal proteolysis and leucyl aminopeptidase
      activity, IRAP recruitment, as well as fusion of phagosomes with endosomes and
      lysosomes are all impaired. These data suggest that STIM1-dependent Ca2+
      signalling promotes the delivery of endolysosomal enzymes to phagosomes to enable
      efficient cross-presentation.

PMID- 29176620
TI  - Cellular microRNA networks regulate host dependency of hepatitis C virus
      infection.
AB  - Cellular microRNAs (miRNAs) have been shown to regulate hepatitis C virus (HCV)
      replication, yet a systematic interrogation of the repertoire of miRNAs impacting
      HCV life cycle is lacking. Here we apply integrative functional genomics
      strategies to elucidate global HCV-miRNA interactions. Through genome-wide miRNA
      mimic and hairpin inhibitor phenotypic screens, and miRNA-mRNA transcriptomics
      analyses, we identify three proviral and nine antiviral miRNAs that interact with
      HCV. These miRNAs are functionally linked to particular steps of HCV life cycle
      and related viral host dependencies. Further mechanistic studies demonstrate that
      miR-25, let-7, and miR-130 families repress essential HCV co-factors, thus
      restricting viral infection at multiple stages. HCV subverts the antiviral
      actions of these miRNAs by dampening their expression in cell culture models and
      HCV-infected human livers. This comprehensive HCV-miRNA interaction map provides
      fundamental insights into HCV-mediated pathogenesis and unveils molecular
      pathways linking RNA biology to viral infections.

PMID- 29176623
TI  - Microneedle-array patches loaded with dual mineralized protein/peptide particles
      for type 2 diabetes therapy.
AB  - The delivery of therapeutic peptides for diabetes therapy is compromised by short
      half-lives of drugs with the consequent need for multiple daily injections that
      reduce patient compliance and increase treatment cost. In this study, we
      demonstrate a smart exendin-4 (Ex4) delivery device based on microneedle (MN)
      array patches integrated with dual mineralized particles separately containing
      Ex4 and glucose oxidase (GOx). The dual mineralized particle-based system can
      specifically release Ex4 while immobilizing GOx as a result of the differential
      response to the microenvironment induced by biological stimuli. In this manner,
      the system enables glucose-responsive and closed-loop release to significantly
      improve Ex4 therapeutic performance. Moreover, integration of mineralized
      particles can enhance the mechanical strength of alginate-based MN by
      crosslinking to facilitate skin penetration, thus supporting painless and non
      invasive transdermal administration. We believe this smart glucose-responsive Ex4
      delivery holds great promise for type 2 diabetes therapy by providing safe, long
      term, and on-demand Ex4 therapy.

PMID- 29176624
TI  - A statistical image analysis framework for pore-free islands derived from
      heterogeneity distribution of nuclear pore complexes.
AB  - Nuclear pore complexes (NPCs) maintain cellular homeostasis by mediating
      nucleocytoplasmic transport. Although cyclin-dependent kinases (CDKs) regulate
      NPC assembly in interphase, the location of NPC assembly on the nuclear envelope
      is not clear. CDKs also regulate the disappearance of pore-free islands, which
      are nuclear envelope subdomains; this subdomain gradually disappears with
      increase in homogeneity of the NPC in response to CDK activity. However, a causal
      relationship between pore-free islands and NPC assembly remains unclear. Here, we
      elucidated mechanisms underlying NPC assembly from a new perspective by focusing
      on pore-free islands. We proposed a novel framework for image-based analysis to
      automatically determine the detailed 'landscape' of pore-free islands from a
      large quantity of images, leading to the identification of NPC intermediates that
      appear in pore-free islands with increased frequency in response to CDK activity.
      Comparison of the spatial distribution between simulated and the observed NPC
      intermediates within pore-free islands showed that their distribution was
      spatially biased. These results suggested that the disappearance of pore-free
      islands is highly related to de novo NPC assembly and indicated the existence of
      specific regulatory mechanisms for the spatial arrangement of NPC assembly on
      nuclear envelopes.

PMID- 29176625
TI  - Silica formation with nanofiber morphology via helical display of the silaffin R5
      peptide on a filamentous bacteriophage.
AB  - Biological systems often generate unique and useful structures, which can have
      industrial relevance either as direct components or as an inspiration for
      biomimetic materials. For fabrication of nanoscale silica structures, we explored
      the use of the silaffin R5 peptide from Cylindrotheca fusiformis expressed on the
      surface of the fd bacteriophage. By utilizing the biomineralizing peptide
      component displayed on the bacteriophage surface, we found that low
      concentrations (0.09 mg/mL of the R5 bacteriophage, below the concentration range
      used in other studies) could be used to create silica nanofibers. An additional
      benefit of this approach is the ability of our R5-displaying phage to form silica
      materials without the need for supplementary components, such as aminopropyl
      triethoxysilane, that are typically used in such processes. Because this method
      for silica formation can occur under mild conditions when implementing our R5
      displaying phage system, we may provide a relatively simple, economical, and
      environmentally friendly process for creating silica nanomaterials.

PMID- 29176627
TI  - Functional anatomy of a giant toothless mandible from a bird-like dinosaur:
      Gigantoraptor and the evolution of the oviraptorosaurian jaw.
AB  - The Oviraptorosauria are a group of theropod dinosaurs that diverged from the
      typical carnivorous theropod diet. It includes two main lineages - Caenagnathidae
      and Oviraptoridae - that display a number of differences in mandibular
      morphology, but little is known about their functional consequences, hampering
      our understanding of oviraptorosaurian dietary evolution. This study presents the
      first in-depth description of the giant toothless mandible of Gigantoraptor, the
      only well-preserved stemward caenagnathid mandible. This mandible shows the
      greatest relative beak depth among caenagnathids, which is an adaptation seen in
      some modern birds for processing harder seeds. The presence of a lingual
      triturating shelf in caenagnathids more crownward than Gigantoraptor suggests a
      possible increased specialization towards shearing along this lineage. Like other
      oviraptorosaurs, the possession of a dorsally convex articular glenoid in
      Gigantoraptor indicates that propalinal jaw movement was probably an important
      mechanism for food processing, as in Sphenodon and dicynodonts. Oviraptorid
      mandibles were more suited for producing powerful bites (e.g. crushing-related)
      compared to caenagnathids: oviraptorids generally possess a deeper, more
      downturned beak, a taller coronoid process prominence and a larger medial
      mandibular fossa. This disparity in caenagnathid and oviraptorid mandible
      morphology potentially suggests specialization towards two different feeding
      styles - shearing and crushing-related mechanisms respectively.

PMID- 29176626
TI  - Systems genetics identifies a role for Cacna2d1 regulation in elevated
      intraocular pressure and glaucoma susceptibility.
AB  - Glaucoma is a multi-factorial blinding disease in which genetic factors play an
      important role. Elevated intraocular pressure is a highly heritable risk factor
      for primary open angle glaucoma and currently the only target for glaucoma
      therapy. Our study helps to better understand underlying genetic and molecular
      mechanisms that regulate intraocular pressure, and identifies a new candidate
      gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic,
      pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure
      significantly. Because our study utilizes a genetically diverse population of
      mice with known sequence variants, we are able to determine that the intraocular
      pressure-lowering effect of pregabalin is dependent on the Cacna2d1 haplotype.
      Using human genome-wide association study (GWAS) data, evidence for association
      of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is
      found. Importantly, these results demonstrate that our systems genetics approach
      represents an efficient method to identify genetic variation that can guide the
      selection of therapeutic targets.

PMID- 29176628
TI  - Identification of the pheromone biosynthesis genes from the sex pheromone gland
      transcriptome of the diamondback moth, Plutella xylostella.
AB  - The diamondback moth was estimated to increase costs to the global agricultural
      economy as the global area increase of Brassica vegetable crops and oilseed rape.
      Sex pheromones traps are outstanding tools available in Integrated Pest
      Management for many years and provides an effective approach for DBM population
      monitoring and control. The ratio of two major sex pheromone compounds shows
      geographical variations. However, the limitation of our information in the DBM
      pheromone biosynthesis dampens our understanding of the ratio diversity of
      pheromone compounds. Here, we constructed a transcriptomic library from the DBM
      pheromone gland and identified genes putatively involved in the fatty acid
      biosynthesis, pheromones functional group transfer, and beta-oxidation enzymes.
      In addition, odorant binding protein, chemosensory protein and pheromone binding
      protein genes encoded in the pheromone gland transcriptome, suggest that female
      DBM moths may receive odors or pheromone compounds via their pheromone gland and
      ovipositor system. Tissue expression profiles further revealed that two ALR,
      three DES and one FAR5 genes were pheromone gland tissue biased, while some
      chemoreception genes expressed extensively in PG, pupa, antenna and legs tissues.
      Finally, the candidate genes from large-scale transcriptome information may be
      useful for characterizing a presumed biosynthetic pathway of the DBM sex
      pheromone.

PMID- 29176629
TI  - Genomic data reveal a loss of diversity in two species of tuco-tucos (genus
      Ctenomys) following a volcanic eruption.
AB  - Marked reductions in population size can trigger corresponding declines in
      genetic variation. Understanding the precise genetic consequences of such
      reductions, however, is often challenging due to the absence of robust pre- and
      post-reduction datasets. Here, we use heterochronous genomic data from samples
      obtained before and immediately after the 2011 eruption of the Puyehue-Cordon
      Caulle volcanic complex in Patagonia to explore the genetic impacts of this event
      on two parapatric species of rodents, the colonial tuco-tuco (Ctenomys
      sociabilis) and the Patagonian tuco-tuco (C. haigi). Previous analyses using
      microsatellites revealed no post-eruption changes in genetic variation in C.
      haigi, but an unexpected increase in variation in C. sociabilis. To explore this
      outcome further, we used targeted gene capture to sequence over 2,000 putatively
      neutral regions for both species. Our data revealed that, contrary to the
      microsatellite analyses, the eruption was associated with a small but significant
      decrease in genetic variation in both species. We suggest that genome-level
      analyses provide greater power than traditional molecular markers to detect the
      genetic consequences of population size changes, particularly changes that are
      recent, short-term, or modest in size. Consequently, genomic analyses promise to
      generate important new insights into the effects of specific environmental events
      on demography and genetic variation.

PMID- 29176631
TI  - Lack of Adipocyte-Fndc5/Irisin Expression and Secretion Reduces Thermogenesis and
      Enhances Adipogenesis.
AB  - Irisin is a browning-stimulating molecule secreted from the fibronectin type III
      domain containing 5 precursor (FNDC5) by muscle tissue upon exercise stimulation.
      Despite its beneficial role, there is an unmet and clamorous need to discern many
      essential aspects of this protein and its mechanism of action not only as a
      myokine but also as an adipokine. Here we contribute to address this topic by
      revealing the nature and role of FNDC5/irisin in adipose tissue. First, we show
      that FNDC5/irisin expression and secretion are induced by adipocyte
      differentiation and confirm its over-secretion by human obese visceral (VAT) and
      subcutaneous (SAT) adipose tissues. Second, we show how secreted factors from
      human obese VAT and SAT decrease PGC1alpha, FNDC5 and UCP1 gene expression on
      differentiating adipocytes; this effect over UCP1 is blunted by blocking irisin
      in obese secretomes. Finally, by stable gene silencing FNDC5 we reveal that FNDC5
      KO adipocytes show reduced UCP1 expression and enhanced adipogenesis.

PMID- 29176632
TI  - Tuning magnetic properties for domain wall pinning via localized metal diffusion.
AB  - Precise control of domain wall displacement in nanowires is essential for
      application in domain wall based memory and logic devices. Currently, domain
      walls are pinned by creating topographical notches fabricated by lithography. In
      this paper, we propose localized diffusion of non-magnetic metal into
      ferromagnetic nanowires by annealing induced mixing as a non-topographical
      approach to form pinning sites. As a first step to prove this new approach,
      magnetodynamic properties of permalloy (Ni80Fe20) films coated with different
      capping layers such as Ta, Cr, Cu and Ru were investigated. Ferromagnetic
      resonance (FMR), and anisotropy magnetoresistance (AMR) measurements were carried
      out after annealing the samples at different temperatures (T an ). The saturation
      magnetization of Ni80Fe20 film decreased, and damping constant increased with T
      an . X-Ray photoelectron spectroscopy results confirmed increased diffusion of Cr
      into the middle of Ni80Fe20 layers with T an . The resistance vs magnetic field
      measurements on nanowires showed intriguing results.

PMID- 29176630
TI  - Break-induced replication promotes formation of lethal joint molecules dissolved
      by Srs2.
AB  - Break-induced replication (BIR) is a DNA double-strand break repair pathway that
      leads to genomic instabilities similar to those observed in cancer. BIR proceeds
      by a migrating bubble where asynchrony between leading and lagging strand
      synthesis leads to accumulation of long single-stranded DNA (ssDNA). It remains
      unknown how this ssDNA is prevented from unscheduled pairing with the template,
      which can lead to genomic instability. Here, we propose that uncontrolled Rad51
      binding to this ssDNA promotes formation of toxic joint molecules that are
      counteracted by Srs2. First, Srs2 dislodges Rad51 from ssDNA preventing
      promiscuous strand invasions. Second, it dismantles toxic intermediates that have
      already formed. Rare survivors in the absence of Srs2 rely on structure-specific
      endonucleases, Mus81 and Yen1, that resolve toxic joint-molecules. Overall, we
      uncover a new feature of BIR and propose that tight control of ssDNA accumulated
      during this process is essential to prevent its channeling into toxic structures
      threatening cell viability.

PMID- 29176633
TI  - Epidemiology and Predictors of NTM Pulmonary Infection in Taiwan - a
      Retrospective, Five-Year Multicenter Study.
AB  - Multicenter, longitudinal studies on nontuberculous mycobacteria (NTM) pulmonary
      infection (PI) are lacking. This study provides a 5-year epidemiological overview
      of NTM-PI in Taiwan and investigated its predictors. The clinical relevance of
      each respiratory NTM isolate in six hospitals between 2008 and 2014 was
      determined according to current guidelines. Recurrent episodes were judged by
      serial bacteriological results. New episodes of NTM-PI and pulmonary colonization
      (PC) occurring since 2010 were analyzed. Logistic regression analysis was
      performed to identify the predictors of NTM-PI. Between 2010 and 2014, the
      incidence rate of NTM-PI was 46.0 episodes per 100,000 hospital-based patient
      years. Mycobacterium avium intracellulare complex (MAC) was predominant in
      Northern Taiwan, whereas MAC and M. abscessus were copredominant in Southern
      Taiwan. Multiple episodes occurred in 9.5% of NTM-PI patients. No female
      predominance was observed, except for MAC-PI. Previous pulmonary tuberculosis and
      chronic obstructive pulmonary disease (COPD) were the most common pulmonary
      comorbidities and independent risk factors for NTM-PI. Other risk factors
      included M. kansasii, M. abscessus, and southern Taiwan. Geographical variation
      of NTM-PI exists in Taiwan. Clinicians should keep a high suspicion on NTM-PI in
      the risk population. In endemic area of tuberculosis and COPD, there may be no
      female predominance in NTM-PI.

PMID- 29176634
TI  - PsiQuaSP-A library for efficient computation of symmetric open quantum systems.
AB  - In a recent publication we showed that permutation symmetry reduces the numerical
      complexity of Lindblad quantum master equations for identical multi-level systems
      from exponential to polynomial scaling. This is important for open system
      dynamics including realistic system bath interactions and dephasing in, for
      instance, the Dicke model, multi-Lambda system setups etc. Here we present an
      object-oriented C++ library that allows to setup and solve arbitrary quantum
      optical Lindblad master equations, especially those that are permutationally
      symmetric in the multi-level systems. PsiQuaSP (Permutation symmetry for
      identical Quantum Systems Package) uses the PETSc package for sparse linear
      algebra methods and differential equations as basis. The aim of PsiQuaSP is to
      provide flexible, storage efficient and scalable code while being as user
      friendly as possible. It is easily applied to many quantum optical or quantum
      information systems with more than one multi-level system. We first review the
      basics of the permutation symmetry for multi-level systems in quantum master
      equations. The application of PsiQuaSP to quantum dynamical problems is
      illustrated with several typical, simple examples of open quantum optical
      systems.

PMID- 29176635
TI  - Atomistic simulation of the measurement of mechanical properties of gold nanorods
      by AFM.
AB  - Mechanical properties of nanoscale objects can be measured with an atomic force
      microscope (AFM) tip. However, the continuum models typically used to relate the
      force measured at a certain indentation depth to quantities such as the elastic
      modulus, may not be valid at such small scales, where the details of atomistic
      processes need to be taken into account. On the other hand, molecular dynamics
      (MD) simulations of nanoindentation, which can offer understanding at an
      atomistic level, are often performed on systems much smaller than the ones
      studied experimentally. Here, we present large scale MD simulations of the
      nanoindentation of single crystal and penta-twinned gold nanorod samples on a
      silicon substrate, with a spherical diamond AFM tip apex. Both the sample and tip
      sizes and geometries match commercially available products, potentially linking
      simulation and experiment. Different deformation mechanisms, involving the
      creation, migration and annihilation of dislocations are observed depending on
      the nanorod crystallographic structure and orientation. Using the Oliver-Pharr
      method, the Young's moduli of the (100) terminated and (110) terminated single
      crystal nanorods, and the penta-twinned nanorod, have been determined to be 103
      +/- 2, 140 +/- 4 and 108 +/- 2 GPa, respectively, which is in good agreement with
      bending experiments performed on nanowires.

PMID- 29176636
TI  - Genetic and clinical characteristics in Japanese hereditary breast and ovarian
      cancer: first report after establishment of HBOC registration system in Japan.
AB  - The hereditary breast and ovarian cancer (HBOC) registration system of Japan was
      established by the Japanese HBOC Consortium. The first trial was registered in
      2015 in four institutions to which some registration committee members belonged.
      We analyzed the information of 830 Japanese pedigrees, who underwent BRCA1/2
      genetic testing, including mutation carriers with BRCA1 (N = 127) and BRCA2 (N =
      115), and their families. The mutation-positive rate was 19.7%. Variants of
      uncertain significance were found in 6.5% of all individuals subjected to genetic
      testing for BRCA1/2. Compared to the United States, Japan had a higher mutation
      positive rate in most categories, except for the groups with male breast cancer.
      Among the intrinsic subtypes of BRCA1-associated breast cancers, 75.8% were
      triple-negative. The incidence rate of contralateral breast cancer in BRCA1/2
      mutation carriers was 0.99%/year. Among 240 mutation carriers, 26 and 62 patients
      underwent risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy
      (RRSO), respectively; the respective frequencies of occult cancer were 7.1 and
      3.2%. Metachronous breast cancer after RRM or peritoneal cancer after RRSO was
      not observed during the follow-up period. The nationwide registration system
      began last year and the system enables follow-up analysis in Japan.

PMID- 29176637
TI  - Coordinated response of the Desulfovibrio desulfuricans 27774 transcriptome to
      nitrate, nitrite and nitric oxide.
AB  - The sulfate reducing bacterium Desulfovibrio desulfuricans inhabits both the
      human gut and external environments. It can reduce nitrate and nitrite as
      alternative electron acceptors to sulfate to support growth. Like other sulphate
      reducing bacteria, it can also protect itself against nitrosative stress caused
      by NO generated when nitrite accumulates. By combining in vitro experiments with
      bioinformatic and RNA-seq data, metabolic responses to nitrate or NO and how
      nitrate and nitrite reduction are coordinated with the response to nitrosative
      stress were revealed. Although nitrate and nitrite reduction are tightly
      regulated in response to substrate availability, the global responses to nitrate
      or NO were largely regulated independently. Multiple NADH dehydrogenases,
      transcription factors of unknown function and genes for iron uptake were
      differentially expressed in response to electron acceptor availability or
      nitrosative stress. Amongst many fascinating problems for future research, the
      data revealed a YtfE orthologue, Ddes_1165, that is implicated in the repair of
      nitrosative damage. The combined data suggest that three transcription factors
      coordinate this regulation in which NrfS-NrfR coordinates nitrate and nitrite
      reduction to minimize toxicity due to nitrite accumulation, HcpR1 serves a global
      role in regulating the response to nitrate, and HcpR2 regulates the response to
      nitrosative stress.

PMID- 29176638
TI  - Recursive Exponentially Weighted N-way Partial Least Squares Regression with
      Recursive-Validation of Hyper-Parameters in Brain-Computer Interface
      Applications.
AB  - A tensor-input/tensor-output Recursive Exponentially Weighted N-Way Partial Least
      Squares (REW-NPLS) regression algorithm is proposed for high dimension multi-way
      (tensor) data treatment and adaptive modeling of complex processes in real-time.
      The method unites fast and efficient calculation schemes of the Recursive
      Exponentially Weighted PLS with the robustness of tensor-based approaches.
      Moreover, contrary to other multi-way recursive algorithms, no loss of
      information occurs in the REW-NPLS. In addition, the Recursive-Validation method
      for recursive estimation of the hyper-parameters is proposed instead of
      conventional cross-validation procedure. The approach was then compared to state
      of-the-art methods. The efficiency of the methods was tested in
      electrocorticography (ECoG) and magnetoencephalography (MEG) datasets. The
      algorithms are implemented in software suitable for real-time operation. Although
      the Brain-Computer Interface applications are used to demonstrate the methods,
      the proposed approaches could be efficiently used in a wide range of tasks beyond
      neuroscience uniting complex multi-modal data structures, adaptive modeling, and
      real-time computational requirements.

PMID- 29176639
TI  - Enhancement of Power Output by using Alginate Immobilized Algae in
      Biophotovoltaic Devices.
AB  - We report for the first time a photosynthetically active algae immobilized in
      alginate gel within a fuel cell design for generation of bioelectricity. The
      algal-alginate biofilm was utilized within a biophotovoltaics (BPV) device
      developed for direct bioelectricity generation from photosynthesis. A peak power
      output of 0.289 mWm-2 with an increase of 18% in power output compared to
      conventional suspension culture BPV device was observed. The increase in maximum
      power density was correlated to the maximum relative electron transport rate
      (rETRm). The semi-dry type of photosynthetically active biofilm proposed in this
      work may offer significantly improved performances in terms of fuel cell design,
      bioelectricity generation, oxygen production and CO2 reduction.

PMID- 29176640
TI  - Identification of differentially expressed miRNAs in the fatty liver of Landes
      goose (Anser anser).
AB  - Unlike mammals, in palmipedes de novo lipogenesis from diet takes place mostly in
      the liver. The French Landes Goose is famous for its high capacity and
      susceptibility to fatty liver production. While miRNAs play a critical role in
      the posttranscriptional regulation of gene expression, miRNAs that are involved
      in the regulation of goose hepatic steatosis have yet to be elucidated. Using
      high-throughput sequencing, we analyzed miRNAs expression profile of Landes goose
      liver after overfeeding for 21 days. Aan-miR-122-5p was the most frequently
      sequenced known miRNA, but it was unchanged after overfeeding. Compared with
      normal liver, we identified that 16 conserved miRNAs were up-regulated while the
      other 9 conserved miRNAs were down-regulated in fatty livers. Many of their
      predicted target genes played key roles in metabolic pathways leading to the
      development of hepatic steatosis in the goose by KEGG pathways analysis. ACSL1
      and ELOVL6 were critical genes in hepatic lipid metabolism and had opposite
      expression patterns with aan-miR-203a and aan-miR-125b-5p, respectively. And we
      validated that aan-miR-203a and aan-miR-125b-5p might involve in the regulation
      of hepatic lipid metabolism by targeting ACSL1 and ELOVL6, respectively. These
      results add to our current understanding of the regulation network in goose lipid
      metabolism.

PMID- 29176641
TI  - Anaerobic microsites have an unaccounted role in soil carbon stabilization.
AB  - Soils represent the largest carbon reservoir within terrestrial ecosystems. The
      mechanisms controlling the amount of carbon stored and its feedback to the
      climate system, however, remain poorly resolved. Global carbon models assume that
      carbon cycling in upland soils is entirely driven by aerobic respiration; the
      impact of anaerobic microsites prevalent even within well-drained soils is missed
      within this conception. Here, we show that anaerobic microsites are important
      regulators of soil carbon persistence, shifting microbial metabolism to less
      efficient anaerobic respiration, and selectively protecting otherwise
      bioavailable, reduced organic compounds such as lipids and waxes from
      decomposition. Further, shifting from anaerobic to aerobic conditions leads to a
      10-fold increase in volume-specific mineralization rate, illustrating the
      sensitivity of anaerobically protected carbon to disturbance. The vulnerability
      of anaerobically protected carbon to future climate or land use change thus
      constitutes a yet unrecognized soil carbon-climate feedback that should be
      incorporated into terrestrial ecosystem models.

PMID- 29176642
TI  - Insight into partial agonism by observing multiple equilibria for ligand-bound
      and Gs-mimetic nanobody-bound beta1-adrenergic receptor.
AB  - A complex conformational energy landscape determines G-protein-coupled receptor
      (GPCR) signalling via intracellular binding partners (IBPs), e.g., Gs and beta
      arrestin. Using 13C methyl methionine NMR for the beta1-adrenergic receptor, we
      identify ligand efficacy-dependent equilibria between an inactive and pre-active
      state and, in complex with Gs-mimetic nanobody, between more and less active
      ternary complexes. Formation of a basal activity complex through ligand-free
      nanobody-receptor interaction reveals structural differences on the cytoplasmic
      receptor side compared to the full agonist-bound nanobody-coupled form,
      suggesting that ligand-induced variations in G-protein interaction underpin
      partial agonism. Significant differences in receptor dynamics are observed
      ranging from rigid nanobody-coupled states to extensive MUs-to-ms timescale
      dynamics when bound to a full agonist. We suggest that the mobility of the full
      agonist-bound form primes the GPCR to couple to IBPs. On formation of the ternary
      complex, ligand efficacy determines the quality of the interaction between the
      rigidified receptor and an IBP and consequently the signalling level.

PMID- 29176643
TI  - Development of a quantitative NS1-capture enzyme-linked immunosorbent assay for
      early detection of yellow fever virus infection.
AB  - Yellow fever is an arboviral disease that causes thousands of deaths every year
      in Africa and the Americas. However, few commercial diagnostic kits are
      available. Non-structural protein 1 (NS1) is an early marker of several
      flavivirus infections and is widely used to diagnose dengue virus (DENV)
      infection. Nonetheless, little is known about the dynamics of Yellow fever virus
      (YFV) NS1 expression and secretion, to encourage its use in diagnosis. To tackle
      this issue, we developed a quantitative NS1-capture ELISA specific for YFV using
      a monoclonal antibody and recombinant NS1 protein. This test was used to quantify
      NS1 in mosquito and human cell line cultures infected with vaccine and wild YFV
      strains. Our results showed that NS1 was detectable in the culture supernatants
      of both cell lines; however, a higher concentration was maintained as cell
      associated rather than secreted into the extracellular milieu. A panel of 73
      human samples was used to demonstrate the suitability of YFV NS1 as a diagnostic
      tool, resulting in 80% sensitivity, 100% specificity, a 100% positive predictive
      value and a 95.5% negative predictive value compared with RT-PCR. Overall, the
      developed NS1-capture ELISA showed potential as a promising assay for the
      detection of early YF infection.

PMID- 29176644
TI  - A rapid flow strategy for the oxidative cyanation of secondary and tertiary
      amines via C-H activation.
AB  - An efficient continuous flow protocol has been developed for bond C-H activation
      which promotes the alpha-cyanation of secondary and tertiary amines using
      magnetic nano-ferrites.

PMID- 29176645
TI  - T cell receptor beta-chains display abnormal shortening and repertoire sharing in
      type 1 diabetes.
AB  - Defects in T cell receptor (TCR) repertoire are proposed to predispose to
      autoimmunity. Here we show, by analyzing >2 * 108 TCRB sequences of circulating
      naive, central memory, regulatory and stem cell-like memory CD4+ T cell subsets
      from patients with type 1 diabetes and healthy donors, that patients have shorter
      TCRB complementarity-determining region 3s (CDR3), in all cell subsets,
      introduced by increased deletions/reduced insertions during VDJ rearrangement.
      High frequency of short CDR3s is also observed in unproductive TCRB sequences,
      which are not subjected to thymic culling, suggesting that the shorter CDR3s
      arise independently of positive/negative selection. Moreover, TCRB CDR3
      clonotypes expressed by autoantigen-specific CD4+ T cells are shorter compared
      with anti-viral T cells, and with those from healthy donors. Thus, early events
      in thymic T cell development and repertoire generation are abnormal in type 1
      diabetes, which suggest that short CDR3s increase the potential for self
      recognition, conferring heightened risk of autoimmune disease.

PMID- 29176646
TI  - An Open Software Platform for the Automated Design of Paper-Based Microfluidic
      Devices.
AB  - Paper-based microfluidic devices have many applications in biomedical and
      environmental analysis. However, the process of prototyping device designs can be
      tedious, error-prone, and time-consuming. Here, we present a cross-platform, open
      source software tool-AutoPAD-developed to quickly create and modify device
      designs and provide a free alternative to commercial design software. The
      capabilities that we designed to be inherent to AutoPAD (e.g., automatic zone
      alignment and design refactoring) highlight its potential use in nearly any paper
      based microfluidic device application and for creating nearly any desired design,
      which we demonstrate through the recreation of numerous device designs from the
      literature.

PMID- 29176647
TI  - MRI Simulation Study Investigating Effects of Vessel Topology, Diffusion, and
      Susceptibility on Transverse Relaxation Rates Using a Cylinder Fork Model.
AB  - Brain vasculature is conventionally represented as straight cylinders when
      simulating blood oxygenation level dependent (BOLD) contrast effects in
      functional magnetic resonance imaging (fMRI). In reality, the vasculature is more
      complicated with branching and coiling especially in tumors. Diffusion and
      susceptibility changes can also introduce variations in the relaxation mechanisms
      within tumors. This study introduces a simple cylinder fork model (CFM) and
      investigates the effects of vessel topology, diffusion, and susceptibility on the
      transverse relaxation rates R2* and R2. Simulations using Monte Carlo methods
      were performed to quantify R2* and R2 by manipulating the CFM at different
      orientations, bifurcation angles, and rotation angles. Other parameters of the
      CFM were chosen based on physiologically relevant values: vessel diameters (~2-10
      um), diffusion rates (1 * 10-11-1 * 10-9 m2/s), and susceptibility values (3 * 10
      8-4 * 10-7 cgs units). R2* and R2 measurements showed a significant dependence on
      the bifurcation and rotation angles in several scenarios using different vessel
      diameters, orientations, diffusion rates, and susceptibility values. The angular
      dependence of R2* and R2 using the CFM could potentially be exploited as a tool
      to differentiate between normal and tumor vessels. The CFM can also serve as the
      elementary building block to simulate a capillary network reflecting realistic
      topological features.

PMID- 29176648
TI  - Evidence for PII with NAGK interaction that regulates Arg synthesis in the
      microalga Myrmecia incisa in response to nitrogen starvation.
AB  - To understand why most eukaryotic microalgae accumulate lipids during nitrogen
      starvation stress, a gene, MiglnB, encoding PII, a signal transduction protein,
      was cloned from the arachidonic acid-rich microalga Myrmecia incisa Reisigl.
      Similarly to its homologues, MiPII contains three conserved T-, B-, and C-loops.
      In the presence of abundant Mg2+, ATP, and Gln, MiPII upregulates Arg
      biosynthesis by interacting with the rate-limiting enzyme, MiNAGK, as evidenced
      by yeast two-hybrid, co-immunoprecipitation assays, and kinetics analysis of
      enzyme-catalyzed reactions. However, this interaction of MiPII with MiNAGK is
      reversed by addition of 2-oxoglutarate (2-OG). Moreover, this interaction is
      present in the chloroplasts of M. incisa, as illustrated cytologically by both
      immunoelectron microscopy and agroinfiltration of Nicotiana benthamiana leaves to
      determine the subcellular localization of MiPII with MiNAGK. During the process
      of nitrogen starvation, soluble Arg levels in M. incisa are modulated by a change
      in MiNAGK enzymatic activity, both of which are significantly correlated (r =
      0.854). A model for the manipulation of Arg biosynthesis via MiPII in M. incisa
      chloroplasts in response to nitrogen starvation is proposed. The ATP and 2-OG
      saved from Arg biosynthesis is thus suggested to facilitate the accumulation of
      fatty acids and triacylglycerol in M. incisa during exposure to nitrogen
      starvation.

PMID- 29176649
TI  - No evidence for social immunity in co-founding queen associations.
AB  - Ant queens often associate to found new colonies, yet the benefits of this
      behaviour remain unclear. A major hypothesis is that queens founding in groups
      are protected by social immunity and can better resist disease than solitary
      queens, due to mutual grooming, sharing of antimicrobials, or higher genetic
      diversity among their workers. We tested this hypothesis by manipulating the
      number of queens in incipient colonies of Lasius niger and measuring their
      resistance to the fungal entomopathogen Metarhizium brunneum. We found no
      evidence for social immunity in associations of founding queens. First, co
      founding queens engaged in self-grooming, but performed very little allo-grooming
      or trophallaxis. Second, co-founding queens did not exhibit higher pathogen
      resistance than solitary queens, and their respective workers did not differ in
      disease resistance. Finally, queens founding in groups increased their investment
      in a component of individual immunity, as expected if they do not benefit from
      social immunity but respond to a higher risk of disease. Overall, our results
      provide no evidence that joint colony founding by L. niger queens increases their
      ability to resist fungal pathogens.

PMID- 29176650
TI  - Association of rs6983267 at 8q24, HULC rs7763881 polymorphisms and serum lncRNAs
      CCAT2 and HULC with colorectal cancer in Egyptian patients.
AB  - The impact of HULC rs7763881 on colorectal cancer (CRC) susceptibility is not yet
      known. Also, the biological function of the cancer-related rs6983267 remains
      unclear. We investigated the association of these SNPs with the risk of CRC and
      adenomatous polyps (AP), their correlation with CCAT2 and HULC expression, and
      the potential of serum CCAT2 and HULC as biomarkers for CRC. 120 CRC patients, 30
      AP patients, and 96 healthy controls were included. Genotyping and serum lncRNAs
      were assayed by qPCR. Studied SNPs were not associated with AP susceptibility.
      rs6983267 GG was associated with increased CRC risk, whereas rs7763881 AC was
      protective. rs7763881 and rs6983267 CT haplotype was protective. Serum CCAT2 and
      HULC were upregulated in CRC and AP patients versus controls and discriminated
      these groups by ROC analysis. rs6983267 GG and rs7763881 AA patients demonstrated
      higher serum CCAT2 and HULC compared with GT/TT and AC, respectively. rs6983267
      and serum HULC predicted CRC diagnosis among non-CRC groups (AP + controls) by
      multivariate analysis. Studied SNPs or serum long noncoding RNAs weren't
      correlated with nodal or distant metastasis. In conclusion, rs6983267 and
      rs7763881 are potential genetic markers of CRC predisposition and correlate with
      serum CCAT2 and HULC, two novel potential non-invasive diagnostic biomarkers for
      CRC.

PMID- 29176651
TI  - Exosomal cargo including microRNA regulates sensory neuron to macrophage
      communication after nerve trauma.
AB  - Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs)
      occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron
      cell bodies release extracellular vesicles, including exosomes containing miRs,
      upon activity. We demonstrate that miR-21-5p is released in the exosomal fraction
      of cultured DRG following capsaicin activation of TRPV1 receptors. Pure sensory
      neuron-derived exosomes released by capsaicin are readily phagocytosed by
      macrophages in which an increase in miR-21-5p expression promotes a pro
      inflammatory phenotype. After nerve injury in mice, miR-21-5p is upregulated in
      DRG neurons and both intrathecal delivery of a miR-21-5p antagomir and
      conditional deletion of miR-21 in sensory neurons reduce neuropathic
      hypersensitivity as well as the extent of inflammatory macrophage recruitment in
      the DRG. We suggest that upregulation and release of miR-21 contribute to sensory
      neuron-macrophage communication after damage to the peripheral nerve.

PMID- 29176652
TI  - A Distinct Endocytic Mechanism of Functionalized-Silica Nanoparticles in Breast
      Cancer Stem Cells.
AB  - Nanoparticles provide new fields for life medical science application, including
      targeted-drug delivery and cancer treatment. To maximize the delivery efficiency
      of nanoparticle, one must understand the uptake mechanism of nanoparticle in
      cells, which may determine their ultimate fate and localization in cells.
      Recently, the proposed-cancer stem cell (CSC) theory has been attracted great
      attention and regarded as new targets for the new nanodrug developmet and cancer
      therapies. The interaction between nanoparticles and cancer cells has been
      extensively studied, but the uptake mechanism of nanoparticles in CSCs has
      received little attention. Here, we use the pharmacological inhibitors of major
      endocytic pathways to study the silica nanoparticle (SiNP) uptake mechanisms in
      the human breast adenocarcinoma cell line (MCF-7) and MCF-7-derived breast cancer
      stem cells (BCSCs). The results demonstrate that the uptake of SiNPs,
      particularly amino-functionalized SiNPs, in MCF-7 cells is strongly affected by
      the actin depolymerization, whereas BCSCs more strongly inhibit the amino
      functionalized SiNP uptake after the scavenger receptor disruption. These
      findings indicate a distinct endocytic mechanism of functionalized SiNPs in
      BCSCs, which is significant for designing ideal nanosized drug delivery systems
      and improving the selectivity for CSC-targeted therapy.

PMID- 29176653
TI  - Estrogen induces c-Kit and an aggressive phenotype in a model of invasive lobular
      breast cancer.
AB  - Among the molecular subtypes of breast cancer are luminal (A or B) estrogen
      receptor positive (ER+), HER2+, and triple negative (basal-like). In addition to
      the molecular subtypes, there are 18 histologic breast cancer subtypes classified
      on appearance, including invasive lobular breast carcinoma (ILC), which are 8-15%
      of all breast cancers and are largely ER+ tumors. We used a new model of ER+ ILC,
      called BCK4. To determine the estrogen regulated genes in our ILC model, we
      examined BCK4 xenograft tumors from mice supplemented with or without estrogen
      using gene expression arrays. Approximately 3000 genes were regulated by estrogen
      in vivo. Hierarchical cluster analyses of the BCK4 derived tumors compared with
      ER+ and ER- breast cancer cell lines show the estrogen treated BCK4 tumors group
      with ER- breast cancers most likely due to a high proliferation score, while
      tumors from cellulose supplemented mice were more related to ER+ breast tumor
      cells. To elucidate genes regulated in vitro by estrogen in BCK4 cells, we
      performed expression profiling using Illumina arrays of the BCK4 cell line,
      treated with or without estrogen in vitro. A set of ~200 overlapping genes were
      regulated by estrogen in the BCK4 cell line and xenograft tumors, and pathway
      analysis revealed that the c-Kit pathway might be a target to reduce estrogen
      induced proliferation. Subsequent studies found that inhibition of c-Kit activity
      using imatinib mesylate (Gleevec(r)) blocked estrogen mediated stimulation of
      BCK4 tumors and BCK4 cells in vitro as effectively as the anti-estrogen
      fulvestrant (Faslodex(r)). Decreased expression of c-Kit using shRNA also
      decreased baseline and estrogen induced proliferation in vitro and in vivo. These
      studies are the first to indicate that c-Kit inhibition is an effective approach
      to target c-Kit+ ILC.

PMID- 29176654
TI  - Programmed biomolecule delivery to enable and direct cell migration for
      connective tissue repair.
AB  - Dense connective tissue injuries have limited repair, due to the paucity of cells
      at the wound site. We hypothesize that decreasing the density of the local
      extracellular matrix (ECM) in conjunction with releasing chemoattractive signals
      increases cellularity and tissue formation after injury. Using the knee meniscus
      as a model system, we query interstitial cell migration in the context of
      migratory barriers using a novel tissue Boyden chamber and show that a gradient
      of platelet-derived growth factor-AB (PDGF-AB) expedites migration through native
      tissue. To implement these signals in situ, we develop nanofibrous scaffolds with
      distinct fiber fractions that sequentially release active collagenase (to
      increase ECM porosity) and PDGF-AB (to attract endogenous cells) in a localized
      and coordinated manner. We show that, when placed into a meniscal defect, the
      controlled release of collagenase and PDGF-AB increases cellularity at the
      interface and within the scaffold, as well as integration with the surrounding
      tissue.

PMID- 29176655
TI  - Incidence and risk of respiratory tract infection associated with specific drug
      therapy in pulmonary arterial hypertension: a systematic review.
AB  - Specific drug therapy has been proven to improve functional capacity and slow
      disease progression in pulmonary arterial hypertension (PAH), regretfully with
      the data on the risk of respiratory tract infection (RTI) associated with
      specific drug therapy being limited. Databases of Medline, Embase, Cochrane
      Library and the ClinicalTrials.gov Website were searched for randomized
      controlled trials (RCTs) that reported the RTI data of PAH-specific drug therapy
      in patients. The primacy outcome was assessed by employing a fixed-effects model.
      Totally, 24 trials involving 6307 patients were included in the analysis. PAH
      specific drug therapy was not significantly associated with the increased risk of
      both RTI (19.4% vs. 21.1% RR 1.02, 95%CI 0.92-1.14, P = 0.69) and serious RTI
      (4.3% vs. 5.0% RR 0.99, 95%CI 0.77-1.26, P = 0.93) compared to placebo. The
      results were consistent across the key subgroups. No heterogeneity between the
      studies (I2 = 35.8% for RTI, and I2 = 0.0% for serious RTI) and no publication
      bias was identified. In conclusion, no significant increase in RTI had been found
      in PAH-specific drug therapy when compared with placebo. Whereas, RTI in PAH
      patients is still worthy of clinical attention.

PMID- 29176656
TI  - Clinical trials: Treatment of HCV-infected patients with advanced kidney disease.

PMID- 29176658
TI  - Hypertension: Salt: the microbiome, immune function and hypertension.

PMID- 29176659
TI  - Non-destructive evaluation of UV pulse laser-induced damage performance of fused
      silica optics.
AB  - The surface laser damage performance of fused silica optics is related to the
      distribution of surface defects. In this study, we used chemical etching assisted
      by ultrasound and magnetorheological finishing to modify defect distribution in a
      fused silica surface, resulting in fused silica samples with different laser
      damage performance. Non-destructive test methods such as UV laser-induced
      fluorescence imaging and photo-thermal deflection were used to characterize the
      surface defects that contribute to the absorption of UV laser radiation. Our
      results indicate that the two methods can quantitatively distinguish differences
      in the distribution of absorptive defects in fused silica samples subjected to
      different post-processing steps. The percentage of fluorescence defects and the
      weak absorption coefficient were strongly related to the damage threshold and
      damage density of fused silica optics, as confirmed by the correlation curves
      built from statistical analysis of experimental data. The results show that non
      destructive evaluation methods such as laser-induced fluorescence and photo
      thermal absorption can be effectively applied to estimate the damage performance
      of fused silica optics at 351 nm pulse laser radiation. This indirect evaluation
      method is effective for laser damage performance assessment of fused silica
      optics prior to utilization.

PMID- 29176657
TI  - Dyslipidaemia in nephrotic syndrome: mechanisms and treatment.
AB  - Nephrotic syndrome is a highly prevalent disease that is associated with high
      morbidity despite notable advances in its treatment. Many of the complications of
      nephrotic syndrome, including the increased risk of atherosclerosis and
      thromboembolism, can be linked to dysregulated lipid metabolism and
      dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol,
      triglycerides and the apolipoprotein B-containing lipoproteins VLDL and IDL;
      decreased lipoprotein lipase activity in the endothelium, muscle and adipose
      tissues; decreased hepatic lipase activity; and increased levels of the enzyme
      PCSK9. In addition, there is an increase in the plasma levels of immature HDL
      particles and reduced cholesterol efflux. Studies from the past few years have
      markedly improved our understanding of the molecular pathogenesis of nephrotic
      syndrome-associated dyslipidaemia, and also heightened our awareness of the
      associated exacerbated risks of cardiovascular complications, progressive kidney
      disease and thromboembolism. Despite the absence of clear guidelines regarding
      treatment, various strategies are being increasingly utilized, including statins,
      bile acid sequestrants, fibrates, nicotinic acid and ezetimibe, as well as lipid
      apheresis, which seem to also induce partial or complete clinical remission of
      nephrotic syndrome in a substantial percentage of patients. Future potential
      treatments will likely also include inhibition of PCSK9 using recently-developed
      anti-PCSK9 monoclonal antibodies and small inhibitory RNAs, as well as targeting
      newly identified molecular regulators of lipid metabolism that are dysregulated
      in nephrotic syndrome.

PMID- 29176661
TI  - Stable Hydrothermal Waves at Steady State Evaporating Droplet Surface.
AB  - Stable hydrothermal waves (HTWs) are found at a sessile ethanol droplet surface
      under the steady state evaporation. It is different from those which greatly
      decrease with the evaporation time in the transient droplet drying process. This
      study removes the possible effect of shrinking droplet on HTWs. An analysis of
      the dimensionless numbers indicates the increasingly enhanced role of
      thermocapillary instabilities upon raising the substrate temperature. The onset
      HTWs can be continuously maintained under the steady state evaporation
      conditions. Interestingly, the stable number of HTWs follows a linear fitting
      with the dimensionless factor incorporating the normalized temperature difference
      between the substrate and the surroundings and the droplet aspect ratio. The
      temperature heterogeneity of HTWs is intensified by increasing the substrate
      temperature. The stable HTWs exhibit the "one source-to-one sink" propagation at
      lower substrate temperatures. However, such directional traveling, normally
      presented in the transient HTWs in the drying droplet, is changed at the higher
      substrate temperatures due to the newly emerged sources and sinks under the
      steady state conditions.

PMID- 29176660
TI  - Social adversity and epigenetic aging: a multi-cohort study on socioeconomic
      differences in peripheral blood DNA methylation.
AB  - Low socioeconomic status (SES) is associated with earlier onset of age-related
      chronic conditions and reduced life-expectancy, but the underlying biomolecular
      mechanisms remain unclear. Evidence of DNA-methylation differences by SES
      suggests a possible association of SES with epigenetic age acceleration (AA). We
      investigated the association of SES with AA in more than 5,000 individuals
      belonging to three independent prospective cohorts from Italy, Australia, and
      Ireland. Low SES was associated with greater AA (beta = 0.99 years; 95% CI
      0.39,1.59; p = 0.002; comparing extreme categories). The results were consistent
      across different SES indicators. The associations were only partially modulated
      by the unhealthy lifestyle habits of individuals with lower SES. Individuals who
      experienced life-course SES improvement had intermediate AA compared to extreme
      SES categories, suggesting reversibility of the effect and supporting the
      relative importance of the early childhood social environment. Socioeconomic
      adversity is associated with accelerated epigenetic aging, implicating
      biomolecular mechanisms that may link SES to age-related diseases and longevity.

PMID- 29176663
TI  - propr: An R-package for Identifying Proportionally Abundant Features Using
      Compositional Data Analysis.
AB  - In the life sciences, many assays measure only the relative abundances of
      components in each sample. Such data, called compositional data, require special
      treatment to avoid misleading conclusions. Awareness of the need for caution in
      analyzing compositional data is growing, including the understanding that
      correlation is not appropriate for relative data. Recently, researchers have
      proposed proportionality as a valid alternative to correlation for calculating
      pairwise association in relative data. Although the question of how to best
      measure proportionality remains open, we present here a computationally efficient
      R package that implements three measures of proportionality. In an effort to
      advance the understanding and application of proportionality analysis, we review
      the mathematics behind proportionality, demonstrate its application to genomic
      data, and discuss some ongoing challenges in the analysis of relative abundance
      data.

PMID- 29176662
TI  - Minimal residual disease by either flow cytometry or cytogenetics prior to an
      allogeneic hematopoietic stem cell transplant is associated with poor outcome in
      acute myeloid leukemia.
AB  - Relapsed acute myeloid leukemia (AML) is a significant challenge after allogeneic
      hematopoietic cell transplant (HCT). Multiparameter flow cytometry (MFC),
      conventional cytogenetics (CG), and fluorescence in situ hybridization (FISH) are
      routinely performed on bone marrow specimens prior to HCT to assess disease
      status. We questioned the extent by which pre-HCT evidence of minimal residual
      disease (MRD) detected by these standard assays, corresponded with post-HCT
      relapse. We conducted a single center, retrospective study of 166 AML patients
      who underwent HCT. Thirty-eight of one hundred sixty-six (23%) patients in
      complete remission (CR) or CR with incomplete count recovery (CRi) had MRD
      detectable by MFC, CG, or FISH. MRD was more frequently seen in patients with
      poor risk karyotype at diagnosis (P = 0.011). MRD-negative patients (MRDneg) had
      significantly longer overall survival (OS) and relapse-free survival than
      patients who were MRD positive (MRDpos) (P = 0.002 and 0.013, respectively). In
      patients with MRDpos prior to HCT, the presence of acute graft vs. host disease
      (GVHD) (grade >= 2) or chronic GVHD significantly improved progression free
      survival (PFS) (hazard ratio (HR) = 0.053 (95% confidence interval (CI): 0.01
      0.279), P = 0.0005) and OS (HR = 0.211 (95% CI: 0.081-0.547), P = 0.0014).

PMID- 29176664
TI  - GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the
      Cl--sensitive WNK1 kinase.
AB  - The K+-Cl- co-transporter KCC2 (SLC12A5) tunes the efficacy of GABAA receptor
      mediated transmission by regulating the intraneuronal chloride concentration [Cl
      ]i. KCC2 undergoes activity-dependent regulation in both physiological and
      pathological conditions. The regulation of KCC2 by synaptic excitation is well
      documented; however, whether the transporter is regulated by synaptic inhibition
      is unknown. Here we report a mechanism of KCC2 regulation by GABAA receptor
      (GABAAR)-mediated transmission in mature hippocampal neurons. Enhancing GABAAR
      mediated inhibition confines KCC2 to the plasma membrane, while antagonizing
      inhibition reduces KCC2 surface expression by increasing the lateral diffusion
      and endocytosis of the transporter. This mechanism utilizes Cl- as an
      intracellular secondary messenger and is dependent on phosphorylation of KCC2 at
      threonines 906 and 1007 by the Cl--sensing kinase WNK1. We propose this mechanism
      contributes to the homeostasis of synaptic inhibition by rapidly adjusting
      neuronal [Cl-]i to GABAAR activity.

PMID- 29176666
TI  - Depth accuracy of the RealSense F200: Low-cost 4D facial imaging.
AB  - The RealSense F200 represents a new generation of economically viable 4
      dimensional imaging (4D) systems for home use. However, its 3D geometric (depth)
      accuracy has not been clinically tested. Therefore, this study determined the
      depth accuracy of the RealSense, in a cohort of patients with a unilateral facial
      palsy (n = 34), by using the clinically validated 3dMD system as a gold standard.
      The patients were simultaneously recorded with both systems, capturing six
      Sunnybrook poses. This study has shown that the RealSense depth accuracy was not
      affected by a facial palsy (1.48 +/- 0.28 mm), compared to a healthy face (1.46
      +/- 0.26 mm). Furthermore, the Sunnybrook poses did not influence the RealSense
      depth accuracy (p = 0.76). However, the distance of the patients to the RealSense
      was shown to affect the accuracy of the system, where the highest depth accuracy
      of 1.07 mm was measured at a distance of 35 cm. Overall, this study has shown
      that the RealSense can provide reliable and accurate depth data when recording a
      range of facial movements. Therefore, when the portability, low-costs, and
      availability of the RealSense are taken into consideration, the camera is a
      viable option for 4D close range imaging in telehealth.

PMID- 29176665
TI  - Microbial volatile communication in human organotypic lung models.
AB  - We inhale respiratory pathogens continuously, and the subsequent signaling events
      between host and microbe are complex, ultimately resulting in clearance of the
      microbe, stable colonization of the host, or active disease. Traditional in vitro
      methods are ill-equipped to study these critical events in the context of the
      lung microenvironment. Here we introduce a microscale organotypic model of the
      human bronchiole for studying pulmonary infection. By leveraging microscale
      techniques, the model is designed to approximate the structure of the human
      bronchiole, containing airway, vascular, and extracellular matrix compartments.
      To complement direct infection of the organotypic bronchiole, we present a
      clickable extension that facilitates volatile compound communication between
      microbial populations and the host model. Using Aspergillus fumigatus, a
      respiratory pathogen, we characterize the inflammatory response of the
      organotypic bronchiole to infection. Finally, we demonstrate multikingdom,
      volatile-mediated communication between the organotypic bronchiole and cultures
      of Aspergillus fumigatus and Pseudomonas aeruginosa.

PMID- 29176667
TI  - Mesenchymal stem cells derived exosomes and microparticles protect cartilage and
      bone from degradation in osteoarthritis.
AB  - Mesenchymal stem or stromal cells (MSCs) exert chondroprotective effects in
      preclinical models of osteoarthritis (OA). Most of their therapeutic effects are
      mediated via soluble mediators, which can be conveyed within extracellular
      vesicles (EVs). The objective of the study was to compare the respective role of
      exosomes (Exos) or microvesicles/microparticles (MPs) in OA. MPs and Exos were
      isolated from bone marrow murine BM-MSCs through differential centrifugation.
      Effect of MPs or Exos was evaluated on OA-like murine chondrocytes and
      chondroprotection was quantified by RT-qPCR. In OA-like chondrocytes, BM-MSC
      derived MPs and Exos could reinduce the expression of chondrocyte markers (type
      II collagen, aggrecan) while inhibiting catabolic (MMP-13, ADAMTS5) and
      inflammatory (iNOS) markers. Exos and MPs were also shown to protect chondrocytes
      from apoptosis and to inhibit macrophage activation. In vivo, Exos or MPs were
      injected in the collagenase-induced OA (CIOA) model and histomorphometric
      analyses of joints were performed by uCT and confocal laser microscopy. BM-MSCs,
      MPs and Exos equally protected mice from joint damage. In conclusion, MPs and
      Exos exerted similar chondroprotective and anti-inflammatory function in vitro
      and protected mice from developing OA in vivo, suggesting that either Exos or MPs
      reproduced the main therapeutic effect of BM-MSCs.

PMID- 29176668
TI  - A protein interaction mechanism for suppressing the mechanosensitive Piezo
      channels.
AB  - Piezo proteins are bona fide mammalian mechanotransduction channels for various
      cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a
      three-bladed, propeller-like homo-trimer comprising a central pore-module and
      three propeller-structures that might serve as mechanotransduction-modules.
      However, the mechanogating and regulation of Piezo channels remain unclear. Here
      we identify the sarcoplasmic /endoplasmic-reticulum Ca2+ ATPase (SERCA),
      including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2
      strategically suppresses Piezo1 via acting on a 14-residue-constituted
      intracellular linker connecting the pore-module and mechanotransduction-module.
      Mutating the linker impairs mechanogating and SERCA2-mediated modulation of
      Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects
      of SERCA2, demonstrating the key role of the linker in mechanogating and
      regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent
      migration of endothelial cells. Collectively, we identify SERCA-mediated
      regulation of Piezos and the functional significance of the linker, providing
      important insights into the mechanogating and regulation mechanisms of Piezo
      channels.

PMID- 29176669
TI  - Modulation of individual auditory-motor coordination dynamics through
      interpersonal visual coupling.
AB  - The current study investigated whether visual coupling between two people
      producing dance-related movements (requiring whole-body auditory-motor
      coordination) results in interpersonal entrainment and modulates individual
      auditory-motor coordination dynamics. Paired participants performed two kinds of
      coordination tasks - either knee flexion or extension repeatedly with metronome
      beats (Flexion-on-the-beat and Extension-on-the-beat conditions) while standing
      face-to-face or back-to-back to manipulate visual interaction. The results
      indicated that the relative phases between paired participants' movements were
      closer to 0 degrees  and less variable when participants could see each other. In
      addition, visibility of the partner reduced individual differences in the
      dynamics of auditory-motor coordination by modulating coordination variability
      and the frequency of phase transitions from Extension-on-the-beat to Flexion-on
      the-beat. Together, these results indicate that visual coupling takes place when
      paired participants can see each other and leads to interpersonal entrainment
      during rhythmic auditory-motor coordination, which compensates for individual
      differences via behavioural assimilation and thus enables individuals to achieve
      unified and cohesive performances.

PMID- 29176670
TI  - Micro-gun based on laser pulse propulsion.
AB  - This paper proposes a novel "micro-gun" structure for laser pulse propulsion. The
      "micro-bullets" (glass microspheres) are irradiated by a laser pulse with a 10 ns
      duration in a dynamic process. Experimental parameters such as the microsphere
      diameter and the laser pulse energy are varied to investigate their influence on
      laser pulse propulsion. The energy field and spatial intensity distribution in
      the capillary tube were simulated using a three-dimensional finite-difference
      time-domain method. The experimental results demonstrate that the propulsion
      efficiency is dependent on the laser pulse energy and the microsphere size. The
      propulsion modes and sources of the propelling force were confirmed through
      direct observation and theoretical calculation. Waves also generated by light
      pressure and thermal expansions assisted the propulsion.

PMID- 29176671
TI  - Inhibition of Delta-induced Notch signaling using fucose analogs.
AB  - Notch is a cell-surface receptor that controls cell-fate decisions and is
      regulated by O-glycans attached to epidermal growth factor-like (EGF) repeats in
      its extracellular domain. Protein O-fucosyltransferase 1 (Pofut1) modifies EGF
      repeats with O-fucose and is essential for Notch signaling. Constitutive
      activation of Notch signaling has been associated with a variety of human
      malignancies. Therefore, tools that inhibit Notch activity are being developed as
      cancer therapeutics. To this end, we screened L-fucose analogs for their effects
      on Notch signaling. Two analogs, 6-alkynyl and 6-alkenyl fucose, were substrates
      of Pofut1 and were incorporated directly into Notch EGF repeats in cells. Both
      analogs were potent inhibitors of binding to and activation of Notch1 by Notch
      ligands Dll1 and Dll4, but not by Jag1. Mutagenesis and modeling studies suggest
      that incorporation of the analogs into EGF8 of Notch1 markedly reduces the
      ability of Delta ligands to bind and activate Notch1.

PMID- 29176672
TI  - 5-Formylcytosine to cytosine conversion by C-C bond cleavage in vivo.
AB  - Tet enzymes oxidize 5-methyl-deoxycytidine (mdC) to 5-hydroxymethyl-dC (hmdC), 5
      formyl-dC (fdC) and 5-carboxy-dC (cadC) in DNA. It was proposed that fdC and cadC
      deformylate and decarboxylate, respectively, to dC over the course of an active
      demethylation process. This would re-install canonical dC bases at previously
      methylated sites. However, whether such direct C-C bond cleavage reactions at fdC
      and cadC occur in vivo remains an unanswered question. Here we report the
      incorporation of synthetic isotope- and (R)-2'-fluorine-labeled dC and fdC
      derivatives into the genome of cultured mammalian cells. Following the fate of
      these probe molecules using UHPLC-MS/MS provided quantitative data about the
      formed reaction products. The data show that the labeled fdC probe is efficiently
      converted into the corresponding labeled dC, most likely after its incorporation
      into the genome. Therefore, we conclude that fdC undergoes C-C bond cleavage in
      stem cells, leading to the direct re-installation of unmodified dC.

PMID- 29176673
TI  - Phosphoproteomics of cAMP signaling of Bordetella adenylate cyclase toxin in
      mouse dendritic cells.
AB  - The adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella
      pertussis subverts immune functions of host myeloid cells expressing the
      alphaMbeta2 integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of
      cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts
      the innate and adaptive immune functions of phagocytes through unregulated
      production of the key signaling molecule cAMP. We have used phosphoproteomics to
      analyze cAMP signaling of CyaA in murine bone marrow-derived dendritic cells.
      CyaA action resulted in alterations of phosphorylation state of a number of
      proteins that regulate actin cytoskeleton homeostasis, including Mena, Talin-1
      and VASP. CyaA action repressed mTOR signaling through activation of mTORC1
      inhibitors TSC2 and PRAS40 and altered phosphorylation of multiple chromatin
      remodelers, including the class II histone deacetylase HDAC5. CyaA toxin action
      further elicited inhibitory phosphorylation of SIK family kinases involved in
      modulation of immune response and provoked dephosphorylation of the
      transcriptional coactivator CRTC3, indicating that CyaA-promoted nuclear
      translocation of CRTC3 may account for CyaA-induced IL-10 production. These
      findings document the complexity of subversive physiological manipulation of
      myeloid phagocytes by the CyaA toxin, serving in immune evasion of the pertussis
      agent.

PMID- 29176674
TI  - Fast and Reliable Differentiation of Eight Trichinella Species Using a High
      Resolution Melting Assay.
AB  - High resolution melting analysis (HRMA) is a single-tube method, which can be
      carried out rapidly as an additional step following real-time quantitative PCR
      (qPCR). The method enables the differentiation of genetic variation (down to
      single nucleotide polymorphisms) in amplified DNA fragments without sequencing.
      HRMA has previously been adopted to determine variability in the amplified genes
      of a number of organisms. However, only one work to date has focused on
      pathogenic parasites-nematodes from the genus Trichinella. In this study, we
      employed a qPCR-HRMA assay specifically targeting two sequential gene fragments
      cytochrome c oxidase subunit I (COI) and expansion segment V (ESV), in order to
      differentiate 37 single L1 muscle larvae samples of eight Trichinella species. We
      show that qPCR-HRMA based on the mitochondrial COI gene allows differentiation
      between the sequences of PCR products of the same length. This simple, rapid and
      reliable method can be used to identify at the species level single larvae of
      eight Trichinella taxa.

PMID- 29176675
TI  - Strategic inhibition of distractors with visual working memory contents after
      involuntary attention capture.
AB  - Previous research has suggested that visual working memory (VWM) contents had a
      guiding effect on selective attention, and once participants realized that the
      distractors shared the same information with VWM contents in the search task,
      they would strategically inhibit the potential distractors with VWM contents.
      However, previous behavioral studies could not reveal the way how distractors
      with VWM contents are inhibited strategically. By employing the eye-tracking
      technique and a dual-task paradigm, we manipulated the probability of memory
      items occurring as distractors to explore this issue. Consistent with previous
      behavioral studies, the results showed that the inhibitory effect occurred only
      in the high-probability condition, while the guiding effect emerged in the low
      probability condition. More importantly, the eye-movement results indicated that
      in the high-probability condition, once few (even one) distractors with VWM
      contents were captured at first, all the remaining distractors with VWM contents
      would be rejected as a whole. However, in the low-probability condition,
      attention could be captured by the majority of distractors with VWM contents.
      These results suggested that the guiding effect of VWM contents on attention is
      involuntary in the early stage of visual search. After the completion of this
      involuntary stage, the guiding effect of task-irrelevant VWM contents on
      attention could be strategically controlled.

PMID- 29176677
TI  - Organoids model distinct Vitamin E effects at different stages of prostate cancer
      evolution.
AB  - Vitamin E increased prostate cancer risk in the Selenium and Vitamin E Cancer
      Prevention Trial (SELECT) through unknown mechanisms while Selenium showed no
      efficacy. We determined the effects of the SELECT supplements on benign
      (primary), premalignant ( RWPE-1) and malignant (LNCaP) prostate epithelial
      organoids. While the supplements decreased proliferation and induced cell death
      in cancer organoids, they had no effect on the benign organoids. In contrast,
      Vitamin E enhanced cell proliferation and survival in the premalignant organoids
      in a manner that recapitulated the SELECT results. Indeed, while Vitamin E
      induced a pro-proliferative gene expression signature, Selenium alone or combined
      with Vitamin E produced an anti-proliferative signature. The premalignant
      organoids also displayed significant downregulation of glucose transporter and
      glycolytic gene expression pointing to metabolic alterations. Detached RWPE-1
      cells had low ATP levels due to diminished glucose uptake and glycolysis which
      was rescued by Vitamin E through the activation of fatty acid oxidation (FAO).
      FAO inhibition abrogated the ATP rescue, diminished survival of the inner matrix
      detached cells, restoring the normal hollow lumen morphology in Vitamin E treated
      organoids. Organoid models therefore clarify the paradoxical findings from SELECT
      and demonstrate that Vitamin E promotes tumorigenesis in the early stages of
      prostate cancer evolution.

PMID- 29176676
TI  - Ozone Improves the Aromatic Fingerprint of White Grapes.
AB  - Ozone, a powerful oxidative stressor, has been recently used in wine industry as
      sanitizing agent to reduce spoilage microflora on grapes. In this study, we
      evaluated ozone-induced metabolic and molecular responses during postharvest
      grape dehydration. Ozone increased the contents of total volatile organic
      compounds (VOCs), which have a great impact on the organoleptic properties of
      grapes and wines. Among terpenes, responsible for floral and fruity aroma,
      linalool, geraniol and nerol were the major aromatic markers of Moscato bianco
      grapes. They were significantly affected by the long-term ozone treatment,
      increasing their concentration in the last phases of dehydration (>20% weight
      loss). At molecular level, our results demonstrated that both postharvest
      dehydration and ozone exposure induce the biosynthesis of monoterpenes via
      methylerythritol phosphate (MEP) pathway and of aldehydes from lipoxygenase
      hydroperoxide lyase (LOX-HPL) pathway. Therefore, transcriptional changes
      occurred and promoted the over-production of many important volatile compounds
      for the quality of white grapes.

PMID- 29176678
TI  - Isochlorogenic acid C prevents enterovirus 71 infection via modulating redox
      homeostasis of glutathione.
AB  - Enterovirus 71 (EV71) is a key pathogen of hand, foot and mouth disease (HFMD) in
      children under 6 years of age. The antiviral potency of antioxidant
      isochlorogenic acid C (ICAC) extracted from foods was evaluated in cellular and
      animal models. First, the cytotoxicity of ICAC on Vero cells was investigated.
      The viral plaques, cytopathic effects and yield induced by EV71 infection were
      obviously reduced by ICAC, which was consistent with the investigation of VP1
      transcripts and protein expression. Moreover, the mortality, weight loss and limb
      paralysis of mice caused by EV71 challenge were remarkably relieved by ICAC
      injection, which was achieved through decreases in the viral load and cytokine
      secretion in the mouse brain. Further biochemical assays showed that ICAC
      modulated several antioxidant enzymes involved in reduced and oxidized
      glutathione (GSH and GSSG) homeostasis, including glutathione reductase (GR),
      glutathione peroxidase (GPX), and glucose-6-phosphate dehydrogenase (G6PD),
      resulting in restoration of the GSH/GSSG ratio and reactive oxygen species (ROS)
      level. Finally, the antiviral effects of ICAC were dose-dependently disrupted by
      BSO, a biosynthesis inhibitor of GSH. This study indicated that ICAC acted as an
      antioxidant and prevented EV71 infection by modulating the redox homeostasis of
      glutathione.

PMID- 29176679
TI  - Volatile organic compounds from Paenibacillus polymyxa KM2501-1 control
      Meloidogyne incognita by multiple strategies.
AB  - Plant-parasitic nematodes (PPNs) cause serious crop losses worldwide. In this
      study, we investigated the nematicidal factors and the modes and mechanisms of
      action involved in nematode control by Paenibacillus polymyxa KM2501-1. Treatment
      of the second-stage juveniles (J2) juveniles of PPN Meloidogyne incognita with
      the biological control agent KM2501-1 resulted in a mortality of 87.66% in vitro
      and reduced symptoms on tomato by up to 82.61% under greenhouse conditions. We
      isolated 11 volatile organic compounds (VOCs) from strain KM2501-1, of which 8
      had contact nematicidal activity, 6 had fumigant activity, and 5 acted as stable
      chemotactic agents to M. incognita. The VOCs provided a comprehensive strategy
      against PPNs that included "honey-trap", fumigant, attractant and repellent
      modes. Furfural acetone and 2-decanol functioned as "honey-traps" attracting M.
      incognita and then killing it by contact or fumigation. Two other VOCs, 2
      nonanone and 2-decanone, as well as strain KM2501-1 itself, destroyed the
      integrity of the intestine and pharynx. Collectively our results indicate that
      VOCs produced by P. polymyxa KM2501-1 act through diverse mechanisms to control
      M. incognita. Moreover, the novel "honey-trap" mode of VOC-nematode interaction
      revealed in this study extends our understanding of the strategies exploited by
      nematicidal biocontrol agents.

PMID- 29176680
TI  - Identification of novel factors enhancing recombinant protein production in multi
      copy Komagataella phaffii based on transcriptomic analysis of overexpression
      effects.
AB  - The methylotrophic yeast Komagataella phaffii (Pichia pastoris) has been
      developed into a highly successful system for heterologous protein expression in
      both academia and industry. However, overexpression of recombinant protein often
      leads to severe burden on the physiology of K. phaffii and triggers cellular
      stress. To elucidate the global effect of protein overexpression, we set out to
      analyze the differential transcriptome of recombinant strains with 12 copies and
      a single copy of phospholipase A2 gene (PLA 2) from Streptomyces violaceoruber.
      Through GO, KEGG and heat map analysis of significantly differentially expressed
      genes, the results indicated that the 12-copy strain suffered heavy cellular
      stress. The genes involved in protein processing and stress response were
      significantly upregulated due to the burden of protein folding and secretion,
      while the genes in ribosome and DNA replication were significantly downregulated
      possibly contributing to the reduced cell growth rate under protein
      overexpression stress. Three most upregulated heat shock response genes (CPR6,
      FES1, and STI1) were co-overexpressed in K. phaffii and proved their positive
      effect on the secretion of reporter enzymes (PLA2 and prolyl endopeptidase) by
      increasing the production up to 1.41-fold, providing novel helper factors for
      rational engineering of K. phaffii.

PMID- 29176681
TI  - Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies
      from psychotic patients.
AB  - The identification of circulating autoantibodies against neuronal receptors in
      neuropsychiatric disorders has fostered new conceptual and clinical frameworks.
      However, detection reliability, putative presence in different diseases and in
      health have raised questions about potential pathogenic mechanism mediated by
      autoantibodies. Using a combination of single molecule-based imaging approaches,
      we here ascertain the presence of circulating autoantibodies against glutamate
      NMDA receptor (NMDAR-Ab) in about 20% of psychotic patients diagnosed with
      schizophrenia and very few healthy subjects. NMDAR-Ab from patients and healthy
      subjects do not compete for binding on native receptor. Strikingly, NMDAR-Ab from
      patients, but not from healthy subjects, specifically alter the surface dynamics
      and nanoscale organization of synaptic NMDAR and its anchoring partner the
      EphrinB2 receptor in heterologous cells, cultured neurons and in mouse brain.
      Functionally, only patients' NMDAR-Ab prevent long-term potentiation at
      glutamatergic synapses, while leaving NMDAR-mediated calcium influx intact. We
      unveil that NMDAR-Ab from psychotic patients alter NMDAR synaptic transmission,
      supporting a pathogenically relevant role.

PMID- 29176682
TI  - The Neural Basis of Changing Social Norms through Persuasion.
AB  - Social norms regulate behavior, and changes in norms have a great impact on
      society. In most modern societies, norms change through interpersonal
      communication and persuasive messages found in media. Here, we examined the
      neural basis of persuasion-induced changes in attitude toward and away from norms
      using fMRI. We measured brain activity while human participants were exposed to
      persuasive messages directed toward specific norms. Persuasion directed toward
      social norms specifically activated a set of brain regions including temporal
      poles, temporo-parietal junction, and medial prefrontal cortex. Beyond these
      regions, when successful, persuasion away from an accepted norm specifically
      recruited the left middle temporal and supramarginal gyri. Furthermore, in
      combination with data from a separate attitude-rating task, we found that left
      supramarginal gyrus activity represented participant attitude toward norms and
      tracked the persuasion-induced attitude changes that were away from agreement.

PMID- 29176683
TI  - Coronary calcification in adults with Turner syndrome.
AB  - PurposeAdults with Turner syndrome (TS) have an increased predisposition to
      ischemic heart disease. The quantitative relationship between coronary
      atherosclerosis and TS has yet to be established.MethodsA total of 128 females
      (62 with TS) participated in this prospective study. Coronary computed tomography
      angiography was performed to measure coronary calcified plaque burden, and
      prevalent noncalcified plaque burden. Regression analysis was used to study the
      effects of TS and traditional cardiovascular disease risk factors on coronary
      plaque burden.ResultsAdults with TS were 63% more likely to have coronary
      calcifications than controls (odds ratio 1.63, 95% confidence interval: 1.02,
      2.61, P = 0.04), with an age cutoff of 51.7 years for a probability of >50% for
      the presence of coronary calcifications, when compared to 55.7 years in female
      controls. The average age of TS patients with calcified plaques was significantly
      lower than that of controls with calcified plaques (51.5 +/- 8.9 years vs. 60.5
      +/- 7.0 years, P < 0.001). Age increased the likelihood of coronary
      calcifications by 13% per year (odds ratio 1.13, confidence interval 95%: 1.07
      1.19, P < 0.001).ConclusionThis study demonstrates a higher prevalence and
      earlier onset of calcified coronary plaques in TS. These findings have important
      implications for cardiovascular risk assessment and the management of patients
      with TS.

PMID- 29176684
TI  - Acupuncture analgesia involves modulation of pain-induced gamma oscillations and
      cortical network connectivity.
AB  - Recent studies support the view that cortical sensory, limbic and executive
      networks and the autonomic nervous system might interact in distinct manners
      under the influence of acupuncture to modulate pain. We performed a double-blind
      crossover design study to investigate subjective ratings, EEG and ECG following
      experimental laser pain under the influence of sham and verum acupuncture in 26
      healthy volunteers. We analyzed neuronal oscillations and inter-regional
      coherence in the gamma band of 128-channel-EEG recordings as well as heart rate
      variability (HRV) on two experimental days. Pain ratings and pain-induced gamma
      oscillations together with vagally-mediated power in the high-frequency bandwidth
      (vmHF) of HRV decreased significantly stronger during verum than sham
      acupuncture. Gamma oscillations were localized in the prefrontal cortex (PFC),
      mid-cingulate cortex (MCC), primary somatosensory cortex and insula. Reductions
      of pain ratings and vmHF-power were significantly correlated with increase of
      connectivity between the insula and MCC. In contrast, connectivity between left
      and right PFC and between PFC and insula correlated positively with vmHF-power
      without a relationship to acupuncture analgesia. Overall, these findings
      highlight the influence of the insula in integrating activity in limbic-saliency
      networks with vagally mediated homeostatic control to mediate antinociception
      under the influence of acupuncture.

PMID- 29176685
TI  - Orthrozanclus elongata n. sp. and the significance of sclerite-covered taxa for
      early trochozoan evolution.
AB  - Orthrozanclus is a shell-bearing, sclerite covered Cambrian organism of uncertain
      taxonomic affinity, seemingly representing an intermediate between its fellow
      problematica Wiwaxia and Halkieria. Attempts to group these slug-like taxa into a
      single 'halwaxiid' clade nevertheless present structural and evolutionary
      difficulties. Here we report a new species of Orthrozanclus from the early
      Cambrian Chengjiang Lagerstatte. The scleritome arrangement and constitution in
      this material corroborates the link between Orthrozanclus and Halkieria, but not
      with Wiwaxia - and calls into question its purported relationship with molluscs.
      Instead, the tripartite construction of the halkieriid scleritome finds a more
      compelling parallel in the camenellan tommotiids, relatives of the brachiopods
      and phoronids. Such a phylogenetic position would indicate the presence of a
      scleritome in the common ancestor of the three major trochozoan lineages,
      Mollusca, Annelida and Brachiozoa. On this view, the absence of fossil Ediacaran
      sclerites is evidence against any 'Precambrian prelude' to the explosive
      diversification of these phyla in the Cambrian, c. 540-530 million years ago.

PMID- 29176686
TI  - The dynamics of intracellular water constrains glycolytic oscillations in
      Saccharomyces cerevisiae.
AB  - We explored the dynamic coupling of intracellular water with metabolism in yeast
      cells. Using the polarity-sensitive probe 6-acetyl-2-dimethylaminonaphthalene
      (ACDAN), we show that glycolytic oscillations in the yeast S. cerevisiae BY4743
      wild-type strain are coupled to the generalized polarization (GP) function of
      ACDAN, which measures the physical state of intracellular water. We analysed the
      oscillatory dynamics in wild type and 24 mutant strains with mutations in many
      different enzymes and proteins. Using fluorescence spectroscopy, we measured the
      amplitude and frequency of the metabolic oscillations and ACDAN GP in the resting
      state of all 25 strains. The results showed that there is a lower and an upper
      threshold of ACDAN GP, beyond which oscillations do not occur. This critical GP
      range is also phenomenologically linked to the occurrence of oscillations when
      cells are grown at different temperatures. Furthermore, the link between
      glycolytic oscillations and the ACDAN GP value also holds when ATP synthesis or
      the integrity of the cell cytoskeleton is perturbed. Our results represent the
      first demonstration that the dynamic behaviour of a metabolic process can be
      regulated by a cell-wide physical property: the dynamic state of intracellular
      water, which represents an emergent property.

PMID- 29176687
TI  - Avoidance of seismic survey activities by penguins.
AB  - Seismic surveys in search for oil or gas under the seabed, produce the most
      intense man-made ocean noise with known impacts on invertebrates, fish and marine
      mammals. No evidence to date exists, however, about potential impacts on
      seabirds. Penguins may be expected to be particularly affected by loud underwater
      sounds, due to their largely aquatic existence. This study investigated the
      behavioural response of breeding endangered African Penguins Spheniscus demersus
      to seismic surveys within 100 km of their colony in South Africa, using a multi
      year GPS tracking dataset. Penguins showed a strong avoidance of their preferred
      foraging areas during seismic activities, foraging significantly further from the
      survey vessel when in operation, while increasing their overall foraging effort.
      The birds reverted to normal behaviour when the operation ceased, although longer
      term repercussions on hearing capacities cannot be precluded. The rapid
      industrialization of the oceans has increased levels of underwater anthropogenic
      noises globally, a growing concern for a wide range of taxa, now also including
      seabirds. African penguin numbers have decreased by 70% in the last 10 years, a
      strong motivation for precautionary management decisions, including the exclusion
      of seismic exploratory activities within at least 100 km of their breeding
      colonies.

PMID- 29176688
TI  - Elevated moisture stimulates carbon loss from mineral soils by releasing
      protected organic matter.
AB  - Moisture response functions for soil microbial carbon (C) mineralization remain a
      critical uncertainty for predicting ecosystem-climate feedbacks. Theory and
      models posit that C mineralization declines under elevated moisture and
      associated anaerobic conditions, leading to soil C accumulation. Yet, iron (Fe)
      reduction potentially releases protected C, providing an under-appreciated
      mechanism for C destabilization under elevated moisture. Here we incubate
      Mollisols from ecosystems under C3/C4 plant rotations at moisture levels at and
      above field capacity over 5 months. Increased moisture and anaerobiosis initially
      suppress soil C mineralization, consistent with theory. However, after 25 days,
      elevated moisture stimulates cumulative gaseous C-loss as CO2 and CH4 to >150% of
      the control. Stable C isotopes show that mineralization of older C3-derived C
      released following Fe reduction dominates C losses. Counter to theory, elevated
      moisture may significantly accelerate C losses from mineral soils over weeks to
      months-a critical mechanistic deficiency of current Earth system models.

PMID- 29176690
TI  - Fungal endophytes inhabiting mountain-cultivated ginseng (Panax ginseng Meyer):
      Diversity and biocontrol activity against ginseng pathogens.
AB  - Fungal endophytes isolated from mountain-cultivated ginseng (MCG, Panax ginseng
      Meyer) were explored for their diversity and biocontrol activity against ginseng
      pathogens (Alternaria panax, Botrytis cinerea, Cylindrocarpon destructans,
      Pythium sp. and Rhizoctonia solani). A total of 1,300 isolates were isolated from
      three tissues (root, stem and leaf) from MCGs grown in 24 different geographic
      locations in Korea. In total, 129 different fungal isolates were authenticated by
      molecular identification based on internal transcribed spacer (ITS) sequences.
      The fungal endophytes belonged to Ascomycota (81.7%), Basidiomycota (7.08%),
      Zygomycota (10%) and Unknown (1.15%), with 59 genera. Analysis of diversity
      indices across sampling sites suggested species abundance as a function of
      geographical and environmental factors of the locations. Shannon diversity index
      and richness in the different tissues revealed that root tissues are colonized
      more than stem and leaf tissues, and also certain fungal endophytes are tissue
      specific. Assessment of the ethyl acetate extracts from 129 fungal isolates for
      their biocontrol activity against 5 ginseng pathogens revealed that Trichoderma
      polysporum produces the antimcriobial metabolite against all the pathogens. This
      result indicates the promise of its potential usage as a biocontrol agent.

PMID- 29176689
TI  - Critical role of the HDAC6-cortactin axis in human megakaryocyte maturation
      leading to a proplatelet-formation defect.
AB  - Thrombocytopenia is a major side effect of a new class of anticancer agents that
      target histone deacetylase (HDAC). Their mechanism is poorly understood. Here, we
      show that HDAC6 inhibition and genetic knockdown lead to a strong decrease in
      human proplatelet formation (PPF). Unexpectedly, HDAC6 inhibition-induced tubulin
      hyperacetylation has no effect on PPF. The PPF decrease induced by HDAC6
      inhibition is related to cortactin (CTTN) hyperacetylation associated with actin
      disorganization inducing important changes in the distribution of megakaryocyte
      (MK) organelles. CTTN silencing in human MKs phenocopies HDAC6 inactivation and
      knockdown leads to a strong PPF defect. This is rescued by forced expression of a
      deacetylated CTTN mimetic. Unexpectedly, unlike human-derived MKs, HDAC6 and CTTN
      are shown to be dispensable for mouse PPF in vitro and platelet production in
      vivo. Our results highlight an unexpected function of HDAC6-CTTN axis as a
      positive regulator of human but not mouse MK maturation.

PMID- 29176691
TI  - Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance
      via up-regulation of the expression of lncRNA ANRIL in tumour cells.
AB  - Midkine (MK) is a heparin-binding growth factor that promotes carcinogenesis and
      chemoresistance. The tumour microenvironment (TME) can affect chemotherapy
      sensitivity. However, the role of stromal-derived MK, especially in cancer
      associated fibroblasts (CAFs), is unclear. Here, we confirmed that MK decreased
      cisplatin-induced cell death in oral squamous cell carcinoma (OSCC) cells,
      ovarian cancer cells and lung cancer cells. We also isolated primary CAFs (n = 3)
      from OSCC patients and found that CAFs secreted increased levels of MK, which
      abrogated cisplatin-induced cell death. Moreover, MK increased the expression of
      lncRNA ANRIL in the tumour cells. Normal tissues, matched tumour-adjacent tissues
      and OSCC tissues were analysed (n = 60) and showed that lncRNA ANRIL was indeed
      overexpressed during carcinogenesis and correlated with both high TNM stage and
      lymph node metastasis (LNM). Furthermore, lncRNA ANRIL knockdown in tumour cells
      inhibited proliferation, induced apoptosis and increased cisplatin cytotoxicity
      of the tumour cells via impairment of the drug transporters MRP1 and ABCC2, which
      could be restored by treatment with human MK in a caspase-3/BCL-2-dependent
      manner. In conclusion, we firstly describe that CAFs in the TME contribute to the
      high level of MK in tumours and that CAF-derived MK can promote cisplatin
      resistance via the elevated expression of lncRNA ANRIL.

PMID- 29176692
TI  - Changes in gene expression and apoptotic response in Spodoptera exigua larvae
      exposed to sublethal concentrations of Vip3 insecticidal proteins.
AB  - The insecticidal Vip3 proteins from Bacillus thuringiensis (Bt), along with the
      classical Bt Cry proteins, are currently used in Bt-crops to control insect
      pests, since they do not share the same mode of action. Here we characterized the
      response of Spodoptera exigua larvae after Vip3 challenge. The expression profile
      of 47 genes was analyzed in larvae challenged with three concentrations of
      Vip3Ca. Results showed that the up-regulated genes were mainly involved in immune
      response, whereas the down-regulated genes were mainly involved in the digestion
      process. Other mechanisms of cellular response to the damage such as apoptosis
      were analyzed. For this analysis, sections from the midguts were examined by
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.
      The nuclei of the midgut epithelial cells were stained at the highest
      concentration of the Vip3Ca protein and at lower concentrations of Vip3Aa in
      agreement with the different potency of the two proteins. In addition, apoptosis
      was also examined by the analysis of the expression of five caspase genes. The
      present study shows that exposure of S. exigua larvae to sublethal concentrations
      of Vip3 proteins activates different insect response pathways which trigger the
      regulation of some genes, APN shedding, and apoptotic cell death.

PMID- 29176696
TI  - Overcoming hurdles in sharing microbiome data.

PMID- 29176693
TI  - A study of splicing mutations in disorders of sex development.
AB  - The presence of splicing sequence variants in genes responsible for sex
      development in humans may compromise correct biosynthesis of proteins involved in
      the normal development of gonads and external genitalia. In a cohort of Brazilian
      patients, we identified mutations in HSD17B3 and SRD5A2 which are both required
      for human sexual differentiation. A number of these mutations occurred within
      regions potentially critical for splicing regulation. Minigenes were used to
      validate the functional effect of mutations in both genes. We evaluated the c.277
      + 2 T > G mutation in HSD17B3, and the c.544 G > A, c.548-44 T > G and c.278delG
      mutations in SRD5A2. We demonstrated that these mutations altered the splicing
      pattern of these genes. In a genomic era these results illustrate, and remind us,
      that sequence variants within exon-intron boundaries, which are primarily
      identified for diagnostic purposes and have unknown pathogenicity, need to be
      assessed with regards to their impact not only on protein expression, but also on
      mRNA splicing.

PMID- 29176695
TI  - A radical way to die.

PMID- 29176697
TI  - The population genetics of pangenomes.

PMID- 29176694
TI  - Regulatory T cells control toxicity in a humanized model of IL-2 therapy.
AB  - While patient selection and clinical management have reduced high-dose IL-2
      (HDIL2) immunotherapy toxicities, the immune mechanisms that underlie HDIL2
      induced morbidity remain unclear. Here we show that dose-dependent morbidity and
      mortality of IL-2 immunotherapy can be modeled in human immune system (HIS) mice.
      Depletion of human T cell subsets during the HDIL2 treatment reduces toxicity,
      pointing to the central function of T cells. Preferential expansion of effector T
      cells secondary to defective suppressive capacity of regulatory T (Treg) cells
      after HDIL2 therapy further underscores the importance of Treg in the maintenance
      of immune tolerance. IL-2 toxicity is induced by selective depletion or
      inhibition of Treg after LDIL2 therapy, and is ameliorated in HDIL2-treated HIS
      mice receiving the PIM-1 kinase inhibitor, Kaempferol. Modeling IL-2
      pathophysiology in HIS mice offers a means to understand the functions of
      effector and regulatory T cells in immune-mediated toxicities associated with
      cancer immunotherapy.

PMID- 29176698
TI  - The development of cryo-EM and how it has advanced microbiology.

PMID- 29176699
TI  - Tackling host-circuit give and take.

PMID- 29176700
TI  - Pathway towards renewable chemicals.

PMID- 29176701
TI  - Reply to 'The population genetics of pangenomes'.

PMID- 29176702
TI  - Are pangenomes adaptive or not?

PMID- 29176703
TI  - NSD1- and NSD2-damaging mutations define a subset of laryngeal tumors with
      favorable prognosis.
AB  - Squamous cell carcinomas of the head and neck (SCCHN) affect anatomical sites
      including the oral cavity, nasal cavity, pharynx, and larynx. Laryngeal cancers
      are characterized by high recurrence and poor overall survival, and currently
      lack robust molecular prognostic biomarkers for treatment stratification. Using
      an algorithm for integrative clustering that simultaneously assesses gene
      expression, somatic mutation, copy number variation, and methylation, we for the
      first time identify laryngeal cancer subtypes with distinct prognostic outcomes,
      and differing from the non-prognostic laryngeal subclasses reported by The Cancer
      Genome Atlas (TCGA). Although most common laryngeal gene mutations are found in
      both subclasses, better prognosis is strongly associated with damaging mutations
      of the methyltransferases NSD1 and NSD2, with findings confirmed in an
      independent validation cohort consisting of 63 laryngeal cancer patients.
      Intriguingly, NSD1/2 mutations are not prognostic for nonlaryngeal SCCHN. These
      results provide an immediately useful clinical metric for patient stratification
      and prognostication.

PMID- 29176704
TI  - Gas hydrate saturations estimated from pore-and fracture-filling gas hydrate
      reservoirs in the Qilian Mountain permafrost, China.
AB  - Accurate calculation of gas hydrate saturation is an important aspect of gas
      hydrate resource evaluation. The effective medium theory (EMT model), the
      velocity model based on two-phase medium theory (TPT model), and the two
      component laminated media model (TCLM model), are adopted to investigate the
      characteristics of acoustic velocity and gas hydrate saturation of pore- and
      fracture-filling reservoirs in the Qilian Mountain permafrost, China. The
      compressional wave (P-wave) velocity simulated by the EMT model is more
      consistent with actual log data than the TPT model in the pore-filling reservoir.
      The range of the gas hydrate saturation of the typical pore-filling reservoir in
      hole DKXX-13 is 13.0~85.0%, and the average value of the gas hydrate saturation
      is 61.9%, which is in accordance with the results by the standard Archie equation
      and actual core test. The P-wave phase velocity simulated by the TCLM model can
      be transformed directly into the P-wave transverse velocity in a fracture-filling
      reservoir. The range of the gas hydrate saturation of the typical fracture
      filling reservoir in hole DKXX-19 is 14.1~89.9%, and the average value of the gas
      hydrate saturation is 69.4%, which is in accordance with actual core test
      results.

PMID- 29176705
TI  - Disrupted Brain Network in Children with Autism Spectrum Disorder.
AB  - Alterations in brain connectivity have been extensively reported in autism
      spectrum disorder (ASD), while their effects on the topology of brain network are
      still unclear. This study investigated whether and how the brain networks in
      children with ASD were abnormally organized with resting state EEG. Temporal
      synchronization analysis was first applied to capture the aberrant brain
      connectivity. Then brain network topology was characterized by three graph
      analysis methods including the commonly-used weighted and binary graph, as well
      as minimum spanning tree (MST). Whole brain connectivity in ASD group was found
      to be significantly reduced in theta and alpha band compared to typically
      development children (TD). Weighted graph found significantly decreased path
      length together with marginally significantly decreased clustering coefficient in
      ASD in alpha band, indicating a loss of small-world architecture to a random
      network. Such abnormal network topology was also demonstrated in the binary
      graph. In MST analysis, children with ASD showed a significant lower leaf
      fractions with a decrease trend of tree hierarchy in the alpha band, suggesting a
      shift towards line-like decentralized organization in ASD. The altered brain
      network may offer an insight into the underlying pathology of ASD and possibly
      serve as a biomarker that may aid in diagnosis of ASD.

PMID- 29176706
TI  - Simultaneous fabrication of line and dot dual nanopatterns using miktoarm block
      copolymer with photocleavable linker.
AB  - Block copolymers with various nanodomains, such as spheres, cylinders, and
      lamellae, have received attention for their applicability to nanolithography.
      However, those microdomains are determined by the volume fraction of one block.
      Meanwhile, nanopatterns with multiple shapes are required for the next-generation
      nanolithography. Although various methods have been reported to achieve dual
      nanopatterns, all the methods need sophisticated processes using E-beam. Here, we
      synthesized a miktoarm block copolymer capable of cleavage of one block by
      ultraviolet. Original cylindrical nanodomains of synthesized block copolymer were
      successfully transformed to lamellar nanodomains due to the change of molecular
      architecture by ultraviolet. We fabricated dual nanopatterns consisting of dots
      and lines at desired regions on a single substrate. We also prepared dual
      nanopatterns utilizing another phase transformation from spheres to cylinders in
      a block copolymer with higher interaction parameter. Since our concept has
      versatility to any block copolymer, it could be employed as next-generation
      nanolithography.

PMID- 29176707
TI  - Neolithic cultivation of water chestnuts (Trapa L.) at Tianluoshan (7000-6300 cal
      BP), Zhejiang Province, China.
AB  - Water chestnuts (Trapa) are frequently recovered at Neolithic sites along the
      Lower Yangtze River Valley and have been important components of the diets of
      prehistoric people. However, little systematic research has been conducted to
      determine their cultural and dietary importance. Excavations at the Tianluoshan
      site produced large quantities of well-preserved specimens, which provide an
      excellent collection for studying morphological changes with time. Using modern
      wild and domesticated water chestnuts (n = 447) as a reference, we find Neolithic
      samples (n = 481) at Tianluoshan are similar in shape but smaller in size
      compared to the domesticated species Trapa bispinosa. In particular, the
      Tianluoshan water chestnuts have bigger seeds than the wild species Trapa incisa.
      Further, water chestnuts diachronically increased in size at the Tianluoshan site
      with significant differences (one-way, ANOVA) observed for length (p = 7.85E-08),
      height (p = 3.19E-06), thickness (p = 1.2E-13), top diameter (p = 5.04E-08) and
      bottom diameter (p = 1.75E-05) between layers 7 (6700-6500 cal BP) and 6 (6500
      6300 cal BP). These results suggest that water chestnuts were actively selected
      based on size (big), shape (full fruit, two round horns, wide base, etc.) and
      were an important non-cereal crop to the agricultural practices at the
      Tianluoshan site.

PMID- 29176708
TI  - The Abeta oligomer eliminating D-enantiomeric peptide RD2 improves cognition
      without changing plaque pathology.
AB  - While amyloid-beta protein (Abeta) aggregation into insoluble plaques is one of
      the pathological hallmarks of Alzheimer's disease (AD), soluble oligomeric Abeta
      has been hypothesized to be responsible for synapse damage, neurodegeneration,
      learning, and memory deficits in AD. Here, we investigate the in vitro and in
      vivo efficacy of the D-enantiomeric peptide RD2, a rationally designed derivative
      of the previously described lead compound D3, which has been developed to
      efficiently eliminate toxic Abeta42 oligomers as a promising treatment strategy
      for AD. Besides the detailed in vitro characterization of RD2, we also report the
      results of a treatment study of APP/PS1 mice with RD2. After 28 days of treatment
      we observed enhancement of cognition and learning behaviour. Analysis on brain
      plaque load did not reveal significant changes, but a significant reduction of
      insoluble Abeta42. Our findings demonstrate that RD2 was significantly more
      efficient in Abeta oligomer elimination in vitro compared to D3. Enhanced
      cognition without reduction of plaque pathology in parallel suggests that
      synaptic malfunction due to Abeta oligomers rather than plaque pathology is
      decisive for disease development and progression. Thus, Abeta oligomer
      elimination by RD2 treatment may be also beneficial for AD patients.

PMID- 29176709
TI  - Can Niche Modeling and Geometric Morphometrics Document Competitive Exclusion in
      a Pair of Subterranean Rodents (Genus Ctenomys) with Tiny Parapatric
      Distributions?
AB  - Species with similar ecological requirements coexisting in the same geographic
      region are prone to competitively exclude each other. Alternatively, they may
      coexist if character displacement acts to change the niche requirements of one or
      both species. We used two methodological approaches (ecological niche modeling
      [ENM] and geometric morphometrics) to test two hypotheses: given their
      behavioral, morphological, and ecological similarities, one species competitively
      excludes the other; and, character displacement enables their coexistence at two
      sites in which the species are known to occur in sympatry. The results from the
      ENM-based approach did not provide evidence for competitive exclusion; however,
      the morphometric analyses documented displacement in size of C. minutus. This
      result, suggests that C. minutus might exclude C. flamarioni from areas with
      softer soils and higher food availability. We stress the importance of using
      multiple methodological approaches when testing prediction of competitive
      exclusion. However, both methods had limited explanatory power given that the
      focal species possess truly peculiar distributions, being largely parapatric and
      restricted to narrow, small geographic areas with a strange distribution and
      there is a need to search for additional methods. We discuss the idiosyncrasy of
      the ENM-based approach when applied to organisms with subterranean habits.

PMID- 29176710
TI  - Functional analysis of photosynthetic pigment binding complexes in the green alga
      Haematococcus pluvialis reveals distribution of astaxanthin in Photosystems.
AB  - Astaxanthin is a ketocarotenoid produced by photosynthetic microalgae. It is a
      pigment of high industrial interest in acquaculture, cosmetics, and nutraceutics
      due to its strong antioxidant power. Haematococcus pluvialis, a fresh-water
      microalga, accumulates high levels of astaxanthin upon oxidative stress, reaching
      values up to 5% per dry weight. H. pluvialis accumulates astaxanthin in oil
      droplets in the cytoplasm, while the chloroplast volume is reduced. In this work,
      we investigate the biochemical and spectroscopic properties of the H. pluvialis
      pigment binding complexes responsible for light harvesting and energy conversion.
      Our findings demonstrate that the main features of chlorophyll and carotenoid
      binding complexes previously reported for higher plants or Chlamydomonas
      reinhardtii are preserved under control conditions. Transition to astaxanthin
      rich cysts however leads to destabilization of the Photosystems. Surprisingly,
      astaxanthin was found to be bound to both Photosystem I and II, partially
      substituting beta-carotene, and thus demonstrating possible astaxanthin
      biosynthesis in the plastids or transport from the cytoplasm to the chloroplast.
      Astaxanthin binding to Photosystems does not however improve their
      photoprotection, but rather reduces the efficiency of excitation energy transfer
      to the reaction centers. We thus propose that astaxanthin binding partially
      destabilizes Photosystem I and II.

PMID- 29176711
TI  - Exploration of Protein Unfolding by Modelling Calorimetry Data from Reheating.
AB  - Studies of protein unfolding mechanisms are critical for understanding protein
      functions inside cells, de novo protein design as well as defining the role of
      protein misfolding in neurodegenerative disorders. Calorimetry has proven
      indispensable in this regard for recording full energetic profiles of protein
      unfolding and permitting data fitting based on unfolding pathway models. While
      both kinetic and thermodynamic protein stability are analysed by varying scan
      rates and reheating, the latter is rarely used in curve-fitting, leading to a
      significant loss of information from experiments. To extract this information, we
      propose fitting both first and second scans simultaneously. Four most common
      single-peak transition models are considered: (i) fully reversible, (ii) fully
      irreversible, (iii) partially reversible transitions, and (iv) general three
      state models. The method is validated using calorimetry data for chicken egg
      lysozyme, mutated Protein A, three wild-types of haloalkane dehalogenases, and a
      mutant stabilized by protein engineering. We show that modelling of reheating
      increases the precision of determination of unfolding mechanisms, free energies,
      temperatures, and heat capacity differences. Moreover, this modelling indicates
      whether alternative refolding pathways might occur upon cooling. The Matlab-based
      data fitting software tool and its user guide are provided as a supplement.

PMID- 29176712
TI  - Variation in iodine food composition data has a major impact on estimates of
      iodine intake in young children.
AB  - BACKGROUND/OBJECTIVES: The reliability of an estimate of iodine intake is largely
      dependent on the quality of the food composition data. We aimed to assess the
      impact of variations in food composition data for iodine and season on the
      estimates of iodine intake in young children. SUBJECTS/METHODS: Cross-sectional
      dietary intake study of Irish 2-year-olds participating in the Cork BASELINE
      Birth Cohort Study (n=468; 30% of the cohort at the 2-year follow-up) were used
      to assess the impact of variation in iodine food composition data on estimates of
      iodine intake, dietary adequacy and risk of exceeding the tolerable upper intake
      level (UL). RESULTS: Mean (SD) iodine intakes calculated using UK (147 (71)) and
      Irish (177 (93)) food composition data were significantly different (P < 0.001)
      (mean difference (95% confidence interval) = 30 (26-33) ug/day) and largely
      adequate (7-14% below the estimated average requirement). Intakes at the 95th
      percentile were 138% and 173% of the UL using UK and Irish food composition data,
      respectively, of which milk accounted for 106% and 150% of the UL. This
      translated into 22% and 35% of toddlers exceeding the UL, using UK and Irish
      composition data, respectively. The mean (SD) daily intake of cow's milk among
      the 91% of consumers was 309 (208) ml. Intakes of cow's milk at the 75th and 95th
      percentiles were 452 and 706 ml, respectively. Using Irish composition data for
      iodine in cows' milk, a daily intake of 450 ml could result in a toddler
      exceeding the UL from milk alone. CONCLUSIONS: Variability in food composition
      has a large impact on assessments of iodine intake, particularly among young
      children for whom milk contributes a large proportion of their daily nutrient
      intake. Although this is unlikely to result in long-term adverse effects, our
      study highlights the need for development of valid biomarkers of individual
      iodine status.

PMID- 29176713
TI  - Rapid resetting of human peripheral clocks by phototherapy during simulated night
      shift work.
AB  - A majority of night shift workers have their circadian rhythms misaligned to
      their atypical schedule. While bright light exposure at night is known to reset
      the human central circadian clock, the behavior of peripheral clocks under
      conditions of shift work is more elusive. The aim of the present study was to
      quantify the resetting effects of bright light exposure on both central (plasma
      cortisol and melatonin) and peripheral clocks markers (clock gene expression in
      peripheral blood mononuclear cells, PBMCs) in subjects living at night. Eighteen
      healthy subjects were enrolled to either a control (dim light) or a bright light
      group. Blood was sampled at baseline and on the 4th day of simulated night shift.
      In response to a night-oriented schedule, the phase of PER1 and BMAL1 rhythms in
      PBMCs was delayed by ~2.5-3 h (P < 0.05), while no shift was observed for the
      other clock genes and the central markers. Three cycles of 8-h bright light
      induced significant phase delays (P < 0.05) of ~7-9 h for central and peripheral
      markers, except BMAL1 (advanced by +5h29; P < 0.05). Here, we demonstrate in
      humans a lack of peripheral clock adaptation under a night-oriented schedule and
      a rapid resetting effect of nocturnal bright light exposure on peripheral clocks.

PMID- 29176715
TI  - Inhalation Exposure to PM2.5 Counteracts Hepatic Steatosis in Mice Fed High-fat
      Diet by Stimulating Hepatic Autophagy.
AB  - Air pollution is associated with the increased risk of metabolic syndrome. In
      this study, we performed inhalation exposure of mice fed normal chow or a high
      fat diet to airborne fine particulate matters (PM2.5), and then investigated the
      complex effects and mechanisms of inhalation exposure to PM2.5 on hepatic
      steatosis, a precursor or manifestation of metabolic syndrome. Our studies
      demonstrated that inhalation exposure of mice fed normal chow to concentrated
      ambient PM2.5 repressed hepatic transcriptional regulators involved in fatty acid
      oxidation and lipolysis, and thus promoted hepatic steatosis. However, PM2.5
      exposure relieved hepatic steatosis in high-fat diet-induced obese mice. Further
      investigation revealed that inhalation exposure to PM2.5 induced hepatic
      autophagy in mouse livers in a manner depending on the MyD88-mediated
      inflammatory pathway. The counteractive effect of PM2.5 exposure on high-fat diet
      induced hepatic steatosis was mediated through PM2.5-induced hepatic autophagy.
      The findings from this study not only defined the effects and mechanisms of PM2.5
      exposure in metabolic disorders, but also revealed the pleotrophic acts of an
      environmental stressor in a complex stress system relevant to public health.

PMID- 29176714
TI  - Analyses of gut microbiota and plasma bile acids enable stratification of
      patients for antidiabetic treatment.
AB  - Antidiabetic medication may modulate the gut microbiota and thereby alter plasma
      and faecal bile acid (BA) composition, which may improve metabolic health. Here
      we show that treatment with Acarbose, but not Glipizide, increases the ratio
      between primary BAs and secondary BAs and plasma levels of unconjugated BAs in
      treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect
      metabolism. Acarbose increases the relative abundances of Lactobacillus and
      Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing
      the relative abundance of microbial genes involved in BA metabolism. Treatment
      outcomes of Acarbose are dependent on gut microbiota compositions prior to
      treatment. Compared to patients with a gut microbiota dominated by Prevotella,
      those with a high abundance of Bacteroides exhibit more changes in plasma BAs and
      greater improvement in metabolic parameters after Acarbose treatment. Our work
      highlights the potential for stratification of T2D patients based on their gut
      microbiota prior to treatment.

PMID- 29176716
TI  - A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based
      chemical sensor.
AB  - Selective, robust and cost-effective chemical sensors for detecting small
      volatile-organic compounds (VOCs) have widespread applications in industry,
      healthcare and environmental monitoring. Here we design a Pt(II) pincer-type
      material with selective absorptive and emissive responses to methanol and water.
      The yellow anhydrous form converts reversibly on a subsecond timescale to a red
      hydrate in the presence of parts-per-thousand levels of atmospheric water vapour.
      Exposure to methanol induces a similarly-rapid and reversible colour change to a
      blue methanol solvate. Stable smart coatings on glass demonstrate robust
      switching over 104 cycles, and flexible microporous polymer membranes
      incorporating microcrystals of the complex show identical vapochromic behaviour.
      The rapid vapochromic response can be rationalised from the crystal structure,
      and in combination with quantum-chemical modelling, we provide a complete
      microscopic picture of the switching mechanism. We discuss how this multiscale
      design approach can be used to obtain new compounds with tailored VOC selectivity
      and spectral responses.

PMID- 29176717
TI  - High miR-205 expression in normal epithelium is associated with biochemical
      failure - an argument for epithelial crosstalk in prostate cancer?
AB  - Due to insufficient prognostic tools, failure to predict aggressive prostate
      cancer (PC) has left patient selection for radical treatment an unsolved
      challenge. This has resulted in overtreatment with radical therapy. Better
      prognostic tools are urgently warranted. MicroRNAs (miRs) have emerged as
      important regulators of cellular pathways, resulting in altered gene expressions.
      miR-205 has previously been observed downregulated in PC, acting as tumor
      suppressor. Herein, the expression of miR-205 in prostate tissue was examined in
      a large, well-described cohort of 535 Norwegian prostatectomy patients. Using in
      situ hybridization, miR-205 expression was semiquantatively measured in normal
      and tumor tissues from radical prostatectomy specimens. Associations with
      clinicopathological data and PC relapse were calculated. Expression of miR-205
      was lower in tumor epithelium compared to normal epithelium. No association was
      observed between miR-205 expression in primary tumor epithelium and cancer
      relapse. In contrast, high expression of miR-205 in normal epithelium was
      independently associated with biochemical relapse (HR = 1.64, p = 0.003). A
      prognostic importance of miR-205 expression was only found in the normal
      epithelium, raising the hypothesis of epithelial crosstalk between normal and
      tumor epithelium in PC. This finding supports the proposed novel hypothesis of an
      anti-cancerogenous function of normal epithelium in tumor tissue.

PMID- 29176718
TI  - Sorption Hysteresis of Light Hydrocarbons and Carbon Dioxide in Shale and
      Kerogen.
AB  - We present adsorption and desorption isotherms of methane, ethane, propane, n
      butane and iso-butane as well as carbon dioxide for two shales and isolated
      kerogens determined by a gravimetric method. The sorption measurements of two
      shales were performed at three different temperatures, 308.15, 323.15, and 338.15
      K. For the isolated kerogens, the measurements were conducted at 338.15 K.
      Methane and ethane sorption isotherms were measured to 35 bar. Carbon dioxide
      sorption isotherms were studied to 30 bar. Due to the low vapor pressure at room
      temperature, the sorption isotherms of propane, n-butane and iso-butane were
      measured to 8, 2, and 2 bar, respectively. The adsorptions of propane, n-butane,
      and iso-butane were much higher than methane at the highest pressures where the
      measurements were conducted. The adsorption of n-butane was 10 times higher than
      methane by mole at 2 bar, followed by iso-butane and propane. Our data show
      significant adsorption hysteresis in ethane, propane, n-butane and iso-butane.
      The most pronounced hysteresis was found in n-butane and iso-butane. Significant
      hysteresis is attributed to the reversible structural changes of kerogens.
      Dissolution of adsorbates into organic matter may also affect the hysteresis.
      This is the first report of propane and butane sorption isotherms in shales.

PMID- 29176719
TI  - Structural Mechanism of the Oxygenase JMJD6 Recognition by the Extraterminal (ET)
      Domain of BRD4.
AB  - Jumonji domain-containing protein 6 (JMJD6) is a member of the Jumonji C family
      of Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. It possesses unique bi
      functional oxygenase activities, acting as both an arginine demethylase and a
      lysyl-hydroxylase. JMJD6 has been reported to be over-expressed in oral, breast,
      lung, and colon cancers and plays important roles in regulation of transcription
      through interactions with transcription regulator BRD4, histones, U2AF65, Luc7L3,
      and SRSF11. Here, we report a structural mechanism revealed by NMR of JMJD6
      recognition by the extraterminal (ET) domain of BRD4 in that a JMJD6 peptide
      (Lys84-Asn96) adapts an alpha-helix when bound to the ET domain. This
      intermolecular recognition is established through JMJD6 interactions with the
      conserved hydrophobic core of the ET domain, and reinforced by electrostatic
      interactions of JMJD6 with residues in the inter-helical alpha1-alpha2 loop of
      the ET domain. Notably, this mode of ligand recognition is different from that of
      ET domain recognition of NSD3, LANA of herpesvirus, and integrase of MLV, which
      involves formation of an intermolecular amphipathic two- or three- strand
      antiparallel beta sheet. Furthermore, we demonstrate that the association between
      the BRD4 ET domain and JMJD6 likely requires a protein conformational change
      induced by single-stranded RNA binding.

PMID- 29176720
TI  - Invasive plants as potential food resource for native pollinators: A case study
      with two invasive species and a generalist bumble bee.
AB  - It is now well established that invasive plants may induce drifts in the quantity
      and/or quality of floral resources. They are then often pointed out as a
      potential driver of bee decline. However, their impact on bee population remains
      quite unclear and still controversial, as bee responses are highly variable among
      species. Here, we compared the amino acid composition of pollen from three native
      and two invasive plant species included in diets of common pollinators in NW
      Europe. Moreover, the nutritional intake (i.e., pollen and amino acid intakes) of
      Bombus terrestris colonies and the pollen foraging behaviour of workers (i.e.,
      visiting rate, number of foraging trips, weight of pollen loads) were considered.
      We found significant differences in pollen nutrients among the studied species
      according to the plant invasive behaviour. We also found significant differences
      in pollen foraging behaviour according to the plant species, from few to several
      foraging trips carrying small or large pollen loads. Such behavioural differences
      directly impacted the pollen intake but depended more likely on plant morphology
      rather than on plant invasive behaviour. These results suggest that common
      generalist bumble bees might not always suffer from plant invasions, depending on
      their behavioural plasticity and nutritional requirements.

PMID- 29176721
TI  - Interocular Symmetry of Vascular Density and Association with Central Macular
      Thickness of Healthy Adults by Optical Coherence Tomography Angiography.
AB  - In order to analyze the interocular correlation of vascular density, foveal
      avascular zone (FAZ) size, central macular thickness (CMT), and to investigate
      the relationship between vascular density and CMT in normal eyes, retinal
      vascular density in superficial capillary plexus (SCP), deep capillary plexus
      (DCP) and choriocapillaris (CC) networks, FAZ size, and CMT were visualized by
      optical coherence tomography (OCT) angiography. A total of 174 eyes of 87 normal
      Chinese subjects were enrolled in the study. The results showed that FAZ and CMT
      measurements are not statistically significant between right and left eyes, but
      right eyes had higher vascular density in superficial, deep retinal capillary and
      choriocapillaris networks, which might be related with dominant eyes. Spearman
      correlation test revealed a high correlation between right and left eyes for FAZ
      and CMT measurements (r = 0.934; r = 0.935), and a moderate correlation for SCP,
      DCP and CC density (r = 0.402; r = 0.666; r = 0.417). The analysis showed greater
      vascular density with smaller FAZ size, and a high negative relationship between
      FAZ and CMT, which indicates a positive correlation between retinal blood supply
      and retinal thickness.

PMID- 29176722
TI  - Tides in the Last Interglacial: insights from notch geometry and palaeo tidal
      models in Bonaire, Netherland Antilles.
AB  - The study of past sea levels relies largely on the interpretation of sea-level
      indicators. Palaeo tidal notches are considered as one of the most precise sea
      level indicators as their formation is closely tied to the local tidal range. We
      present geometric measurements of modern and palaeo (Marine Isotope Stage (MIS)
      5e) tidal notches on Bonaire (southern Caribbean Sea) and results from two tidal
      simulations, using the present-day bathymetry and a palaeo-bathymetry. We use
      these two tools to investigate changes in the tidal range since MIS 5e. Our
      models show that the tidal range changes most significantly in shallow areas,
      whereas both, notch geometry and models results, suggest that steeper continental
      shelves, such as the ones bordering the island of Bonaire, are less affected to
      changes in tidal range in conditions of MIS 5e sea levels. We use our data and
      results to discuss the importance of considering changes in tidal range while
      reconstructing MIS 5e sea level histories, and we remark that it is possible to
      use hydrodynamic modelling and notch geometry as first-order proxies to assess
      whether, in a particular area, tidal range might have been different in MIS 5e
      with respect to today.

PMID- 29176723
TI  - Potassium Regulation in Medaka (Oryzias latipes) Larvae Acclimated to Fresh
      Water: Passive Uptake and Active Secretion by the Skin Cells.
AB  - Molecular mechanisms of Na+, Cl-, and Ca2+ regulation in ionocytes of fish have
      been well investigated. However, the regulatory mechanism of K+ in fishes has
      been largely unknown. In this study, we investigated the mechanism of K+
      regulation in medaka larvae acclimated to fresh water. Using a scanning ion
      selective electrode technique (SIET) to measure the K+ fluxes at skin cells,
      significant K+ effluxes were found at ionocytes; in contrast, significant K+
      influxes were found at the boundaries between keratinocytes. High K+ water (HK)
      acclimation induced the K+ effluxes at ionocytes and suppressed the K+ influxes
      at keratinocytes. The K+ effluxes of ionocytes were suppressed by VU591,
      bumetanide and ouabain. The K+ influxes of keratinocytes were suppressed by TAP.
      In situ hybridization analysis showed that mRNA of ROMKa was expressed by
      ionocytes in the skin and gills of medaka larvae. Quantitative PCR showed that
      mRNA levels of ROMKa and NKCC1a in gills of adult medaka were upregulated after
      HK acclimation. This study suggests that medaka obtain K+ through a paracellular
      pathway between keratinocytes and extrude K+ through ionocytes; apical ROMKa and
      basolateral NKCC1a are involved in the K+ secretion by ionocytes.

PMID- 29176724
TI  - Novel peptide probes to assess the tensional state of fibronectin fibers in
      cancer.
AB  - Transformations of extracellular matrix (ECM) accompany pathological tissue
      changes, yet how cell-ECM crosstalk drives these processes remains unknown as
      adequate tools to probe forces or mechanical strains in tissues are lacking.
      Here, we introduce a new nanoprobe to assess the mechanical strain of fibronectin
      (Fn) fibers in tissue, based on the bacterial Fn-binding peptide FnBPA5. FnBPA5
      exhibits nM binding affinity to relaxed, but not stretched Fn fibers and is shown
      to exhibit strain-sensitive ECM binding in cell culture in a comparison with an
      established Fn-FRET probe. Staining of tumor tissue cryosections shows large
      regions of relaxed Fn fibers and injection of radiolabeled 111In-FnBPA5 in a
      prostate cancer mouse model reveals specific accumulation of 111In-FnBPA5 in
      tumor with prolonged retention compared to other organs. The herein presented
      approach enables to investigate how Fn fiber strain at the tissue level impacts
      cell signaling and pathological progression in different diseases.

PMID- 29176725
TI  - Distinct neural substrates of visuospatial and verbal-analytic reasoning as
      assessed by Raven's Advanced Progressive Matrices.
AB  - Recent studies revealed spontaneous neural activity to be associated with fluid
      intelligence (gF) which is commonly assessed by Raven's Advanced Progressive
      Matrices, and embeds two types of reasoning: visuospatial and verbal-analytic
      reasoning. With resting-state fMRI data, using global brain connectivity (GBC)
      analysis which averages functional connectivity of a voxel in relation to all
      other voxels in the brain, distinct neural correlates of these two reasoning
      types were found. For visuospatial reasoning, negative correlations were observed
      in both the primary visual cortex (PVC) and the precuneus, and positive
      correlations were observed in the temporal lobe. For verbal-analytic reasoning,
      negative correlations were observed in the right inferior frontal gyrus (rIFG),
      dorsal anterior cingulate cortex and temporoparietal junction, and positive
      correlations were observed in the angular gyrus. Furthermore, an interaction
      between GBC value and type of reasoning was found in the PVC, rIFG and the
      temporal lobe. These findings suggest that visuospatial reasoning benefits more
      from elaborate perception to stimulus features, whereas verbal-analytic reasoning
      benefits more from feature integration and hypothesis testing. In sum, the
      present study offers, for different types of reasoning in gF, first empirical
      evidence of separate neural substrates in the resting brain.

PMID- 29176726
TI  - Author Correction: Dipeptidyl peptidase-4 inhibitors and cancer risk in patients
      with type 2 diabetes: a meta-analysis of randomized clinical trials.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29176727
TI  - Prognostic value of thyroid hormones in acute ischemic stroke - a meta analysis.
AB  - Previous studies on the association between thyroid hormones and prognosis of
      acute ischemic stroke (AIS) reported conflicting results. We conducted a meta
      analysis to assess the prognostic value of thyroid hormones in AIS. The PubMed,
      EMBASE, and Cochrane library databases were searched through May 12, 2017 to
      identify eligible studies on this subject. Out of 2,181 studies retrieved, 11
      studies were finally included with a total number of 3,936 acute stroke patients
      for analysis. Odds ratio (OR) for predicting poor outcome or standardized mean
      difference (SMD) of thyroid hormone levels with 95% confidence intervals (95% CI)
      obtained from the studies were pooled using Review Manager 5.3. From the results,
      in AIS, patients with a poor outcome had lower levels of triiodothyronine (T3)
      and higher thyroxine (T4). Pooled OR confirmed the same association. Our study
      provides statistical evidence supporting the utility of thyroid hormone levels in
      prognosis of acute stroke.

PMID- 29176728
TI  - Similarities between acylcarnitine profiles in large for gestational age newborns
      and obesity.
AB  - Large for gestational age (LGA) newborns have an increased risk of obesity,
      insulin resistance, and metabolic syndrome. Acylcarnitine profiles in obese
      children and adults are characterized by increased levels of C3, C5, and certain
      medium-chain (C12) and long-chain (C14:1 and C16) acylcarnitines. C2 is also
      increased in insulin-resistant states. In this 1-year observational study of 2514
      newborns (246 LGA newborns, 250 small for gestational age (GA) newborns, and 2018
      appropriate for GA newborns), we analyzed and compared postnatal acylcarnitine
      profiles in LGA newborns with profiles described for obese individuals.
      Acylcarnitine analysis was performed by tandem mass spectrometry on dried-blood
      spots collected on day 3 of life. LGA newborns had higher levels of total short
      chain acylcarnitines (p < 0.001), C2 (p < 0.01) and C3 (p < 0.001)
      acylcarnitines, and all C12, C14, and C16 acylcarnitines except C12:1. They also
      had a higher tendency towards carnitine insufficiency (p < 0.05) and carnitine
      deficiency (p < 0.001). No significant differences were observed between LGA
      newborns born to mothers with or without a history of gestational diabetes. This
      novel study describes a postnatal acylcarnitine profile in LGA with higher levels
      of C2, C3, total acylcarnitines, and total short-chain acylcarnitines that is
      characteristic of childhood and adult obesity and linked to an unhealthy
      metabolic phenotype.

PMID- 29176729
TI  - Two-photon polymerization enabled multi-layer liquid crystal phase modulator.
AB  - The performance of liquid crystal (LC) spatial light modulators depends
      critically on the amount of cumulative phase change. However, for regular phase
      modulators, a large phase change comes with a slow time response penalty. A multi
      layer liquid crystal (LC) spatial light modulator offers a large phase change
      while keeping fast response time due to the decoupling between phase change and
      time response through engineered sub-micron scaffold. Here, we demonstrate
      specially designed 2- and 3-layer LC cells which can achieve 4 times and 7 times
      faster response time than that of conventional single-layer LC phase modulator of
      equivalent thickness, respectively. A versatile two-photon laser lithography is
      employed for LC cell scaffolding to accurately verify theoretical predictions
      with experimental measurements.

PMID- 29176731
TI  - ITIMs: episode 1 of the inhibitory saga.

PMID- 29176732
TI  - An extended cluster expansion for ground states of heterofullerenes.
AB  - It is challenging to determine the ground states of heterofullerenes due to the
      numerous isomers. Taking the C60-n B n heterofullerenes (1 <= n <= 4) as an
      example, our first-principles calculations with the isomer enumeration present
      the most stable structure of C57B3, which is energetically favored by 0.73 eV
      than the reported counterpart. It was difficult to conduct the enumeration for
      the isomers with n beyond 4 because of the expensive first-principle
      calculations. Here, we propose a nomenclature to enhance structural recognition
      and adopt an extended cluster expansion to describe the structural stabilities,
      in which the energies of the heterofullerenes with various concentrations are
      predicted by linear combination of the multi-body interactions. Unlike the
      conventional cluster expansion, the interaction parameters are derived from the
      enumeration of C60-n B n (n = 1~4), where there are only 4 coefficients to be
      fitted as a function of composition for the consideration of local bonding. The
      cross-validation scores are 1~2 meV per atom for both C55B5 and C54B6, ensuring
      the ground states obtained from our model are in line with the first-principles
      results. With the help of the structural recognition, the extended cluster
      expansion could be further applied to other binary systems as an effective
      complement to the first-principle calculations.

PMID- 29176730
TI  - The microbiomes of blowflies and houseflies as bacterial transmission reservoirs.
AB  - Blowflies and houseflies are mechanical vectors inhabiting synanthropic
      environments around the world. They feed and breed in fecal and decaying organic
      matter, but the microbiome they harbour and transport is largely uncharacterized.
      We sampled 116 individual houseflies and blowflies from varying habitats on three
      continents and subjected them to high-coverage, whole-genome shotgun sequencing.
      This allowed for genomic and metagenomic analyses of the host-associated
      microbiome at the species level. Both fly host species segregate based on
      principal coordinate analysis of their microbial communities, but they also show
      an overlapping core microbiome. Legs and wings displayed the largest microbial
      diversity and were shown to be an important route for microbial dispersion. The
      environmental sequencing approach presented here detected a stochastic
      distribution of human pathogens, such as Helicobacter pylori, thereby
      demonstrating the potential of flies as proxies for environmental and public
      health surveillance.

PMID- 29176733
TI  - A pH-induced conformational switch in a tyrosine kinase inhibitor identified by
      electronic spectroscopy and quantum chemical calculations.
AB  - Tyrosine kinase inhibitors (TKIs) are a major class of drug utilised in the
      clinic. During transit to their cognate kinases, TKIs will encounter different pH
      environments that could have a major influence on TKI structure. To address this,
      we report UV-Vis spectroscopic and computational studies of the TKI, AG1478, as a
      function of pH. The electronic absorption spectrum of AG1478 shifted by 10 nm
      (from 342 nm to 332 nm) from acid to neutral pH and split into two peaks (at 334
      nm and 345 nm) in highly alkaline conditions. From these transitions, the pKa
      value was calculated as 5.58 +/- 0.01. To compute structures and spectra, time
      dependent density functional theory (TD-DFT) calculations were performed along
      with conductor-like polarizable continuum model (CPCM) to account for implicit
      solvent effect. On the basis of the theoretical spectra, we could assign the
      AG1478 experimental spectrum at acidic pH to a mixture of two twisted conformers
      (71% AG1478 protonated at quinazolyl nitrogen N(1) and 29% AG1478 protonated at
      quinazolyl nitrogen N(3)) and at neutral pH to the neutral planar conformer. The
      AG1478 absorption spectrum (pH 13.3) was fitted to a mixture of neutral (70%) and
      NH-deprotonated species (30%). These studies reveal a pH-induced conformational
      transition in a TKI.

PMID- 29176734
TI  - Spectroscopic detection of halogen bonding resolves dye regeneration in the dye
      sensitized solar cell.
AB  - The interactions between a surface-adsorbed dye and a soluble redox-active
      electrolyte species in the dye-sensitized solar cell has a significant impact on
      the rate of regeneration of photo-oxidized dye molecules and open-circuit voltage
      of the device. Dyes must therefore be designed to encourage these interfacial
      interactions, but experimentally resolving how such weak interactions affect
      electron transfer is challenging. Herein, we use X-ray absorption spectroscopy to
      confirm halogen bonding can exist at the dye-electrolyte interface. Using a known
      series of triphenylamine-based dyes bearing halogen substituents geometrically
      positioned for reaction with halides in solution, halogen bonding was detected
      only in cases where brominated and iodinated dyes were photo-oxidized. This
      result implies that weak intermolecular interactions between photo-oxidized dyes
      and the electrolyte can impact device photovoltages. This result was unexpected
      considering the low concentration of oxidized dyes (less than 1 in 100,000) under
      full solar illumination.

PMID- 29176735
TI  - Interplay between trauma and Pseudomonas entomophila infection in flies: a
      central role of the JNK pathway and of CrebA.
AB  - In mammals, both sterile wounding and infection induce inflammation and activate
      the innate immune system, and the combination of both challenges may lead to
      severe health defects, revealing the importance of the balance between the
      intensity and resolution of the inflammatory response for the organism's fitness.
      Underlying mechanisms remain however elusive. Using Drosophila, we show that,
      upon infection with the entomopathogenic bacterium Pseudomonas entomophila (Pe),
      a sterile wounding induces a reduced resistance and increased host mortality. To
      identify the molecular mechanisms underlying the susceptibility of wounded flies
      to bacterial infection, we analyzed the very first steps of the process by
      comparing the transcriptome landscape of infected (simple hit flies, SH), wounded
      and infected (double hit flies, DH) and wounded (control) flies. We observed that
      overexpressed genes in DH flies compared to SH ones are significantly enriched in
      genes related to stress, including members of the JNK pathway. We demonstrated
      that the JNK pathway plays a central role in the DH phenotype by manipulating the
      Jra/dJun activity. Moreover, the CrebA/Creb3-like transcription factor (TF) and
      its targets were up-regulated in SH flies and we show that CrebA is required for
      mounting an appropriate immune response. Drosophila thus appears as a relevant
      model to investigate interactions between trauma and infection and allows to
      unravel key pathways involved.

PMID- 29176736
TI  - Rama: a machine learning approach for ribosomal protein prediction in plants.
AB  - Ribosomal proteins (RPs) play a fundamental role within all type of cells, as
      they are major components of ribosomes, which are essential for translation of
      mRNAs. Furthermore, these proteins are involved in various physiological and
      pathological processes. The intrinsic biological relevance of RPs motivated
      advanced studies for the identification of unrevealed RPs. In this work, we
      propose a new computational method, termed Rama, for the prediction of RPs, based
      on machine learning techniques, with a particular interest in plants. To perform
      an effective classification, Rama uses a set of fundamental attributes of the
      amino acid side chains and applies a two-step procedure to classify proteins with
      unknown function as RPs. The evaluation of the resultant predictive models showed
      that Rama could achieve mean sensitivity, precision, and specificity of 0.91,
      0.91, and 0.82, respectively. Furthermore, a list of proteins that have no
      annotation in Phytozome v.10, and are annotated as RPs in Phytozome v.12, were
      correctly classified by our models. Additional computational experiments have
      also shown that Rama presents high accuracy to differentiate ribosomal proteins
      from RNA-binding proteins. Finally, two novel proteins of Arabidopsis thaliana
      were validated in biological experiments. Rama is freely available at
      http://inctipp.bioagro.ufv.br:8080/Rama .

PMID- 29176738
TI  - Induction of Immune Surveillance of the Dysmorphogenic Lens.
AB  - The lens has been considered to be an immune privileged site not susceptible to
      the immune processes normally associated with tissue injury and wound repair.
      However, as greater insight into the immune surveillance process is gained, we
      have reevaluated the concept of immune privilege. Our studies using an N-cadherin
      lens-specific conditional knockout mouse, N-cadDeltalens, show that loss of this
      cell-cell junctional protein leads to lens degeneration, necrosis and fibrotic
      change, postnatally. The degeneration of this tissue induces an immune response
      resulting in immune cells populating the lens that contribute to the development
      of fibrosis. Additionally, we demonstrate that the lens is connected to the
      lymphatic system, with LYVE(+) labeling reaching the lens along the suspensory
      ligaments that connect the lens to the ciliary body, providing a potential
      mechanism for the immune circulation. Importantly, we observe that degeneration
      of the lens activates an immune response throughout the eye, including cornea,
      vitreous humor, and retina, suggesting a coordinated protective response in the
      visual system to defects of a component tissue. These studies demonstrate that
      lens degeneration induces an immune response that can contribute to the fibrosis
      that often accompanies lens dysgenesis, a consideration for understanding organ
      system response to injury.

PMID- 29176739
TI  - Preparation of ZnSO4.7H2O using filter cake enriched in calcium and magnesium
      from the process of zinc hydrometallurgy.
AB  - ZnSO4?7H2O was prepared using a filter cake enriched in calcium and magnesium
      that was generated during the process of zinc hydrometallurgy. The study was
      optimized to obtain process parameters. The results show that the optimal acid
      leaching parameters are a solid-to-liquid ratio of 1:3.5, a sulfuric acid
      concentration of 16%, an acid leaching time of 20 min, a final pH of 4.1-4.4, a
      cooling and settling time of 120 min, an oxidation time of 20 min, a stirring
      speed of 300 r/min, a H2O2 dosage of 25 mL/L, a crystallization temperature of 20
      degrees C, and a crystallization time of 60 min. The ZnSO4?7H2O content in the
      product is 98.6%, and the zinc recovery efficiency is 97.5%. This process is
      characterized by simple flow and low cost, while the circulation and accumulation
      problems with calcium and magnesium ions in the zinc hydrometallurgy process are
      also solved.

PMID- 29176737
TI  - cGAS drives noncanonical-inflammasome activation in age-related macular
      degeneration.
AB  - Geographic atrophy is a blinding form of age-related macular degeneration
      characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits
      DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and
      NLRP3-inflammasome activation. How the inflammasome is activated in this
      untreatable disease is largely unknown. Here we demonstrate that RPE degeneration
      in human-cell-culture and mouse models is driven by a noncanonical-inflammasome
      pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires
      cyclic GMP-AMP synthase (cGAS)-dependent interferon-beta production and gasdermin
      D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA
      accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS.
      Moreover, caspase-4, gasdermin D, interferon-beta, and cGAS levels were elevated
      in the RPE in human eyes with geographic atrophy. Collectively, these data
      highlight an unexpected role of cGAS in responding to mobile-element transcripts,
      reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage
      induced inflammasome activation, expand the immune-sensing repertoire of cGAS and
      caspase-4 to noninfectious human disease, and identify new potential targets for
      treatment of a major cause of blindness.

PMID- 29176740
TI  - Research progress in cytokines with chemokine-like function.

PMID- 29176741
TI  - Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid
      transfer proteins.
AB  - This corrects the article DOI: 10.1038/cmi.2017.4.

PMID- 29176742
TI  - TLR7, a third signal for the robust generation of spontaneous germinal center B
      cells in systemic lupus erythematosus.

PMID- 29176743
TI  - HCV immune evasion and regulatory T cell activation: cause or consequence?

PMID- 29176744
TI  - Crucial role of miR-31 in induction of CD8+ T-cell exhaustion and reinforcement
      of type 1 interferon signaling.

PMID- 29176745
TI  - Aged T cells and cardiovascular disease.

PMID- 29176746
TI  - LYVE-1 is 'on stage' now: an emerging player in dendritic cell docking to
      lymphatic endothelial cells.

PMID- 29176748
TI  - Roles of neddylation against viral infections.

PMID- 29176749
TI  - Amino acids 89-96 of Salmonella flagellin: a key site for its adjuvant effect
      independent of the TLR5 signaling pathway.

PMID- 29176747
TI  - The crucial roles of Th17-related cytokines/signal pathways in M. tuberculosis
      infection.
AB  - Interleukin-17 (IL-17), IL-21, IL-22 and IL-23 can be grouped as T helper 17
      (Th17)-related cytokines because they are either produced by Th17/Th22 cells or
      involved in their development. Here, we review Th17-related cytokines/Th17-like
      cells, networks/signals and their roles in immune responses or immunity against
      Mycobacterium tuberculosis (Mtb) infection. Published studies suggest that Th17
      related cytokine pathways may be manipulated by Mtb microorganisms for their
      survival benefits in primary tuberculosis (TB). In addition, there is evidence
      that immune responses of the signal transducer and activator of transcription 3
      (STAT3) signal pathway and Th17-like T-cell subsets are dysregulated or destroyed
      in patients with TB. Furthermore, Mtb infection can impact upstream cytokines in
      the STAT3 pathway of Th17-like responses. Based on these findings, we discuss the
      need for future studies and the rationale for targeting Th17-related
      cytokines/signals as a potential adjunctive treatment.

PMID- 29176751
TI  - Mapping microscale wetting variations on biological and synthetic water-repellent
      surfaces.
AB  - Droplets slip and bounce on superhydrophobic surfaces, enabling remarkable
      functions in biology and technology. These surfaces often contain microscopic
      irregularities in surface texture and chemical composition, which may affect or
      even govern macroscopic wetting phenomena. However, effective ways to quantify
      and map microscopic variations of wettability are still missing, because existing
      contact angle and force-based methods lack sensitivity and spatial resolution.
      Here, we introduce wetting maps that visualize local variations in wetting
      through droplet adhesion forces, which correlate with wettability. We develop
      scanning droplet adhesion microscopy, a technique to obtain wetting maps with
      spatial resolution down to 10 um and three orders of magnitude better force
      sensitivity than current tensiometers. The microscope allows characterization of
      challenging non-flat surfaces, like the butterfly wing, previously difficult to
      characterize by contact angle method due to obscured view. Furthermore, the
      technique reveals wetting heterogeneity of micropillared model surfaces
      previously assumed to be uniform.

PMID- 29176752
TI  - A very large-scale microelectrode array for cellular-resolution
      electrophysiology.
AB  - In traditional electrophysiology, spatially inefficient electronics and the need
      for tissue-to-electrode proximity defy non-invasive interfaces at scales of more
      than a thousand low noise, simultaneously recording channels. Using compressed
      sensing concepts and silicon complementary metal-oxide-semiconductors (CMOS), we
      demonstrate a platform with 65,536 simultaneously recording and stimulating
      electrodes in which the per-electrode electronics consume an area of 25.5 MUm by
      25.5 MUm. Application of this platform to mouse retinal studies is achieved with
      a high-performance processing pipeline with a 1 GB/s data rate. The platform
      records from 65,536 electrodes concurrently with a ~10 uV r.m.s. noise; senses
      spikes from more than 34,000 electrodes when recording across the entire retina;
      automatically sorts and classifies greater than 1700 neurons following visual
      stimulation; and stimulates individual neurons using any number of the 65,536
      electrodes while observing spikes over the entire retina. The approaches
      developed here are applicable to other electrophysiological systems and electrode
      configurations.

PMID- 29176750
TI  - Chemoattractants and cytokines in primary ciliary dyskinesia and cystic fibrosis:
      key players in chronic respiratory diseases.
AB  - Patients with primary ciliary dyskinesia (PCD) and cystic fibrosis (CF), two
      inherited disorders, suffer from recurrent airway infections characterized by
      persistent bacterial colonization and uncontrollable inflammation. Although
      present in high counts, neutrophils fail to clear infection in the airways. High
      levels of C-X-C motif chemokine ligand 8/interleukin-8 (CXCL8/IL-8), the most
      potent chemokine to attract neutrophils to sites of infection, are detected in
      the sputum of both patient groups and might cause the high neutrophil influx in
      the airways. Furthermore, in CF, airway neutrophils are highly activated because
      of the genetic defect and the high levels of proinflammatory chemoattractants and
      cytokines (e.g., CXCL8/IL-8, tumor necrosis factor-alpha and IL-17). The
      overactive state of neutrophils leads to lung damage and fuels the vicious circle
      of infection, excessive inflammation and tissue damage. The inflammatory process
      in CF airways is well characterized, whereas the lung pathology in PCD is far
      less studied. The knowledge of CF lung pathology could be useful to guide
      molecular investigations of the inflammatory processes in PCD lungs. Current
      available therapies can not completely remedy the chronic airway infections in
      these diseases. This review gives an overview of the role that chemoattractants
      and cytokines play in these neutrophil-dominated lung pathologies. Finally, the
      most frequently applied treatments in CF and PCD and new experimental therapies
      to reduce neutrophil-dominated airway inflammation are described.

PMID- 29176753
TI  - Centiloid method evaluation for amyloid PET of subcortical vascular dementia.
AB  - Reference region selection is important for proper amyloid PET analysis,
      especially in subcortical vascular dementia (SVaD) patients. We investigated
      reference region differences between SVaD and Alzheimer's disease (AD) using
      Centiloid scores. In 57 [C-11] Pittsburgh compound B (PiB) positive (+) AD and 23
      PiB (+) SVaD patients, we assessed standardized PiB uptake and Centiloid scores
      in disease-specific cortical regions, with several reference regions: cerebellar
      gray (CG), whole cerebellum (WC), WC with brainstem (WC + B), pons, and white
      matter (WM). We calculated disease group differences from young controls (YC) and
      YC variance according to reference region. SVaD patients showed large effect
      sizes (Cohen's d > 0.8) using all reference regions. WM and pons showed larger YC
      variances than other regions. Findings were similar for AD patients. CG, WC, and
      WC + B, but not WM or pons, are reliable reference regions for amyloid imaging
      analysis in SVaD.

PMID- 29176754
TI  - The O-specific polysaccharide lyase from the phage LKA1 tailspike reduces
      Pseudomonas virulence.
AB  - Pseudomonas phage LKA1 of the subfamily Autographivirinae encodes a tailspike
      protein (LKA1gp49) which binds and cleaves B-band LPS (O-specific antigen, OSA)
      of Pseudomonas aeruginosa PAO1. The crystal structure of LKA1gp49 catalytic
      domain consists of a beta-helix, an insertion domain and a C-terminal discoidin
      like domain. The putative substrate binding and processing site is located on the
      face of the beta-helix whereas the C-terminal domain is likely involved in
      carbohydrates binding. NMR spectroscopy and mass spectrometry analyses of
      degraded LPS (OSA) fragments show an O5 serotype-specific polysaccharide lyase
      specificity. LKA1gp49 reduces virulence in an in vivo Galleria mellonella
      infection model and sensitizes P. aeruginosa to serum complement activity. This
      enzyme causes biofilm degradation and does not affect the activity of
      ciprofloxacin and gentamicin. This is the first comprehensive report on LPS
      degrading lyase derived from a Pseudomonas phage. Biological properties reveal a
      potential towards its applications in antimicrobial design and as a
      microbiological or biotechnological tool.

PMID- 29176755
TI  - Baculovirus-Mediated miR-214 Knockdown Shifts Osteoporotic ASCs Differentiation
      and Improves Osteoporotic Bone Defects Repair.
AB  - Osteoporotic patients often suffer from bone fracture but its healing is
      compromised due to impaired osteogenesis potential of bone marrow-derived
      mesenchymal stem cells (BMSCs). Here we aimed to exploit adipose-derived stem
      cells from ovariectomized rats (OVX-ASCs) for bone healing. We unraveled that OVX
      ASCs highly expressed miR-214 and identified 2 miR-214 targets: CTNNB1 (beta
      catenin) and TAB2. We demonstrated that miR-214 targeting of these two genes
      blocked the Wnt pathway, led to preferable adipogenesis and hindered
      osteogenesis. As a result, OVX-ASCs implantation into OVX rats failed to heal
      critical-size metaphyseal bone defects. We further engineered the OVX-ASCs with a
      novel Cre/loxP-based hybrid baculovirus vector that conferred prolonged
      expression of miR-214 sponge. Gene delivery for miR-214 sponge expression
      successfully downregulated miR-214 levels, activated the Wnt pathway, upregulated
      osteogenic factors beta-catenin/Runx2, downregulated adipogenic factors PPAR
      gamma and C/EBP-alpha, shifted the differentiation propensity towards osteogenic
      lineage, enhanced the osteogenesis of co-cultured OVX-BMSCs, elevated
      BMP7/osteoprotegerin secretion and hindered exosomal miR-214/osteopontin release.
      Consequently, implanting the miR-214 sponge-expressing OVX-ASCs tremendously
      improved bone healing in OVX rats. Co-expression of miR-214 sponge and BMP2
      further synergized the OVX-ASCs-mediated bone regeneration in OVX rats. This
      study implicates the potential of suppressing miR-214 by baculovirus-mediated
      gene delivery in osteoporotic ASCs for regenerative medicine.

PMID- 29176756
TI  - Cryogenic 3D Printing of Super Soft Hydrogels.
AB  - Conventional 3D bioprinting allows fabrication of 3D scaffolds for biomedical
      applications. In this contribution we present a cryogenic 3D printing method able
      to produce stable 3D structures by utilising the liquid to solid phase change of
      a composite hydrogel (CH) ink. This is achieved by rapidly cooling the ink
      solution below its freezing point using solid carbon dioxide (CO2) in an
      isopropanol bath. The setup was able to successfully create 3D complex
      geometrical structures, with an average compressive stiffness of O(1) kPa (0.49
      +/- 0.04 kPa stress at 30% compressive strain) and therefore mimics the
      mechanical properties of the softest tissues found in the human body (e.g. brain
      and lung). The method was further validated by showing that the 3D printed
      material was well matched to the cast-moulded equivalent in terms of mechanical
      properties and microstructure. A preliminary biological evaluation on the 3D
      printed material, coated with collagen type I, poly-L-lysine and gelatine, was
      performed by seeding human dermal fibroblasts. Cells showed good attachment and
      viability on the collagen-coated 3D printed CH. This greatly widens the range of
      applications for the cryogenically 3D printed CH structures, from soft tissue
      phantoms for surgical training and simulations to mechanobiology and tissue
      engineering.

PMID- 29176757
TI  - Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against
      Staphylococcus aureus.
AB  - Chronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa
      frequently fail to respond to antibiotic treatment, leading to significant
      patient morbidity and mortality. Currently, the impact of interspecies
      interaction on S. aureus antibiotic susceptibility remains poorly understood. In
      this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis
      (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus
      susceptibility to bactericidal antibiotics in a variable, strain-dependent manner
      and further identify 3 independent interactions responsible for antagonizing or
      potentiating antibiotic activity against S. aureus. We find that P. aeruginosa
      LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids
      facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4
      hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through
      respiratory inhibition and reduction of cellular ATP. We find that the production
      of each of these factors varies between clinical isolates and corresponds to the
      capacity of each isolate to alter S. aureus antibiotic susceptibility.
      Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn
      infection is potentiated by the presence of a LasA-producing P. aeruginosa
      population. These findings demonstrate that antibiotic susceptibility is complex
      and dependent not only upon the genotype of the pathogen being targeted, but also
      on interactions with other microorganisms in the infection environment.
      Consideration of these interactions will improve the treatment of polymicrobial
      infections.

PMID- 29176758
TI  - Early optimal parenteral nutrition and metabolic acidosis in very preterm
      infants.
AB  - BACKGROUND: It is currently recognized that an optimized nutritional approach,
      consisting of an early and substantial supply of protein and energy by parenteral
      route, may be beneficial for very low birth weight infants and recent guidelines
      endorse this strategy. However, the impact of the enhanced parenteral nutrition
      (PN) on acid-basic balance has never been investigated. The aim of the present
      study is to assess the effect of nutrient intake on acid-base homeostasis in a
      large population of preterm infants on PN. METHODS: This observational study
      described the acid-base profile of very preterm infants (<=29 week's gestation)
      receiving PN during the first week of life. For this purpose three different
      cohorts of infants who received increasing (group 1 to group 3) nutritional
      intakes were considered. Nutrition data were recorded daily and correlated to
      acid-base data (pH, base excess, and lactate). The outcome measure to assess
      metabolic acidosis was the base excess (BE). RESULTS: 161 infants were included.
      1127 daily nutritional records and 795 blood gas data were analyzed. The three
      groups were different with regard to nutritional intravenous intakes. Group 3 in
      particular had a higher mean intake of both amino acids (3.3 +/- 0.8 g/kg/d) and
      lipids (2.8 +/- 1.4 g/kg/d) during the first week of life. Metabolic acidosis was
      more severe in the group with the highest parenteral intake of amino acids and
      lipids: mean BE = -8.7 +/- 3.4 (group 3); -6.4 +/- 3.4 (group 2); -5.1 +/- 3.0
      (group 1)]. At the multivariate analysis the significant risk factors for
      metabolic acidosis were: gestational age, initial base excess, amino acid and
      lipid intravenous intakes. DISCUSSION: Acid-base homeostasis was influenced by
      the nutritional intake. Earlier and higher intravenous amino acid and lipid
      intakes particularly increased the risk of metabolic acidosis. The nutritional
      tolerance was different depending on gestational age, and the smaller infants (24
      26 week's gestation) displayed greater acidotic disequilibrium and a higher need
      of bicarbonate.

PMID- 29176759
TI  - Distinct Trypanosoma cruzi isolates induce activation and apoptosis of human
      neutrophils.
AB  - Neutrophils are critical players in the first line of defense against pathogens
      and in the activation of subsequent cellular responses. We aimed to determine the
      effects of the interaction of Trypanosoma cruzi with human neutrophils, using
      isolates of the two major discrete type units (DTUs) associated with Chagas'
      disease in Latin America (clone Col1.7G2 and Y strain, DTU I and II,
      respectively). Thus, we used CFSE-stained trypomastigotes to measure neutrophil
      T. cruzi interaction, neutrophil activation, cytokine expression and death, after
      infection with Col1.7G2 and Y strain. Our results show that the frequency of
      CFSE+ neutrophils, indicative of interaction, and CFSE intensity on a cell-per
      cell basis were similar when comparing Col1.7G2 and Y strains. Interaction with
      T. cruzi increased neutrophil activation, as measured by CD282, CD284, TNF and IL
      12 expression, although at different levels between the two strains. No change in
      IL-10 expression was observed after interaction of neutrophils with either
      strain. We observed that exposure to Y and Col1.7G2 caused marked neutrophil
      death. This was specific to neutrophils, since interaction of either strain with
      monocytes did not cause death. Our further analysis showed that neutrophil death
      was a result of apoptosis, which was associated with an upregulation of TNF
      receptor, TNF and FasLigand, but not of Fas. Induction of TNF-associated
      neutrophil apoptosis by the different T. cruzi isolates may act as an effective
      common mechanism to decrease the host's immune response and favor parasite
      survival.

PMID- 29176760
TI  - Clostridium difficile flagellin FliC: Evaluation as adjuvant and use in a mucosal
      vaccine against Clostridium difficile.
AB  - The immunogenicity of bacterial flagellin has been reported in different studies.
      By its close interaction with the immune system, the flagellin represents an
      interesting adjuvant and vaccine candidate. Salmonella Typhimurium flagellin has
      already been tested as adjuvant to stimulate mucosal immunity. Here, we assessed
      the ability of Clostridium difficile flagellin FliC to act as a mucosal adjuvant,
      first combined with ovalbumin as antigen and second with a C. difficile surface
      protein, the precursor of the S-layer proteins SlpA. Using ovalbumin as antigen,
      we compared the gut mucosal adjuvanticity of FliC to Salmonella Typhimurium
      flagellin and cholera toxin. Two routes of immunization were tested in a mouse
      model: intra-rectal and intra-peritoneal, following which, gut mucosal and
      systemic antibody responses against ovalbumin (Immunoglobulins G and
      Immunoglobulins A) were analyzed by Enzyme-Linked Immuno Assay in intestinal
      contents and in sera. In addition, ovalbumin-specific immunoglobulin producing
      cells were detected in the intestinal lamina propria by Enzyme-Linked Immunospot.
      Results showed that FliC as adjuvant for immunization targeting ovalbumin was
      able to stimulate a gut mucosal and systemic antibody response independently of
      the immunization route. In order to develop a mucosal vaccine to prevent C.
      difficile intestinal colonization, we assessed in a mouse model the efficacy of
      FliC as adjuvant compared with cholera toxin co-administrated with the C.
      difficile S-layer precursor SlpA as antigen. After challenge, a significant
      decrease of C. difficile intestinal colonization was observed in immunized groups
      compared to the control group. Our results showed that C. difficile FliC could be
      used as adjuvant in mucosal vaccination strategy against C. difficile infections.

PMID- 29176761
TI  - Association of objectively measured arm inclination with shoulder pain: A 6-month
      follow-up prospective study of construction and health care workers.
AB  - OBJECTIVES: The aim was to determine the association of occupational arm
      inclination with shoulder pain in construction and health care workers. METHODS:
      Arm inclination relative to the vertical was measured with an accelerometer
      placed on the dominant upper arm for up to four full days at baseline in 62
      construction workers and 63 health care workers. The pain intensity in the
      shoulder and mechanical and psychosocial work factors were measured by self
      reports at baseline and prospectively after 6 months. The associations between
      exposures and shoulder pain were analyzed with multilevel mixed-effects linear
      regressions. RESULTS: For the total study population working with the dominant
      arm at inclinations > 30 degrees  and >120 degrees  was associated with lower
      levels of shoulder pain both cross-sectionally and after 6 months. Associations
      were attenuated when adjusting for individual and social factors, psychological
      state, and exposure during leisure time, especially for the high inclination
      levels. Analyses, only including subjects with no pain at baseline revealed no
      significant associations. While stratified analysis showed negative associations
      in the construction worker group, there were no significant association in health
      care workers. Compared to the number of hypotheses tested, the number of
      significant findings was low. Adjustment by Bonferroni-correction made almost all
      findings insignificant. CONCLUSIONS: All analyses reflected a negative
      association between arm inclination and shoulder pain, but few analyses showed
      these associations to be statistically significant. If there is a relationship
      between arm inclination and shoulder pain, these findings could indicate that
      pain-avoidance may modify how workers perform their tasks.

PMID- 29176762
TI  - Effect of a prenatal lifestyle intervention on physical activity level in late
      pregnancy and the first year postpartum.
AB  - BACKGROUND: Despite documented health benefits for mother and baby, physical
      activity (PA)-level tends to decline in pregnancy. Overweight/obese and
      physically inactive women are two selected groups at increased risk of pregnancy
      complications. Thus, efficient strategies to maintain or increase PA-level in
      pregnancy and the postpartum period, especially among these women, are warranted.
      This secondary analysis examined the effect of a prenatal lifestyle-intervention
      on PA-level in late pregnancy and the first year postpartum, with subanalysis on
      initially physically active versus inactive and normal-weight versus
      overweight/obese women. METHOD: The Norwegian Fit for Delivery (NFFD) randomized
      controlled trial included healthy primiparous women with singleton pregnancies
      and body mass index (BMI) >=19 kg/m2 assigned to an intervention group, n = 303
      (twice weekly group-exercises and dietary counseling) or a control group, n = 303
      (standard prenatal care). The International Physical Activity Questionnaire short
      form was used to assess PA-levels at inclusion (mean gestational week (GW) 16),
      GW 36, and six and 12 months postpartum. RESULTS: At GW 36, a positive
      intervention-effect with a significant between-group difference in total PA-level
      compared to time of inclusion was found for the total group (530 MET-min/week, p
      = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and
      initially active women (717 MET-min/week, p<0.001). Intervention-effect was
      dependent on exercise-adherence among overweight/obese and inactive women.
      Compared to time of inclusion, the intervention groups maintained total PA-level
      at GW 36, while total PA-level decreased in the control groups. The PA-levels
      increased postpartum, but with no significant differences between the
      randomization groups. CONCLUSION: The NFFD prenatal combined lifestyle
      intervention had a significant effect on TPA-level in late pregnancy among women
      entering pregnancy normal-weight or physically active, thereby preventing the
      downward trend typically seen during pregnancy. Intervention-effect among
      overweight/obese and physically inactive women was, however, dependent on
      exercise-adherence. Long-term intervention-effect was not observed in the
      postpartum period.

PMID- 29176763
TI  - Blood serum metabolome of atopic dermatitis: Altered energy cycle and the markers
      of systemic inflammation.
AB  - Atopic dermatitis is a chronic inflammatory disease which usually starts in the
      early childhood and ends before adulthood. However up to 3% of adults remain
      affected by the disease. The onset and course of the disease is influenced by
      various genetic and environmental factors. Although the immune system has a great
      effect on the outcome of the disease, metabolic markers can also try to explain
      the background of atopic dermatitis. In this study we analyzed the serum of
      patients with atopic dermatitis using both targeted and untargeted metabolomics
      approaches. We found the most significant changes to be related to
      phosphatidylcholines, acylcarnitines and their ratios and a cleavage peptide of
      Fibrinogen A-alpha. These findings that have not been reported before will
      further help to understand this complex disease.

PMID- 29176764
TI  - Interleukin 27 is increased in carotid atherosclerosis and promotes NLRP3
      inflammasome activation.
AB  - AIM: Interleukin-27 (IL-27) is involved in different inflammatory diseases;
      however, its role in atherosclerosis is unclear. In this study we investigated
      the expression of IL-27 and its receptor in patients with carotid atherosclerosis
      and if IL-27 could modulate the inflammatory effects of the NLRP3 inflammasome in
      vitro. METHODS: Plasma IL-27 was measured by enzyme immunoassay in patients with
      carotid stenosis (n = 140) and in healthy controls (n = 19). Expression of IL-27
      and IL-27R was analyzed by quantitative PCR and immunohistochemistry in plaques
      from patients and in non-atherosclerotic vessels. THP-1 monocytes, primary
      monocytes and peripheral blood mononuclear cells (PBMCs) were used to study
      effects of IL-27 in vitro. RESULTS: Our main findings were: (i) Plasma levels of
      IL-27 were significantly elevated in patients with carotid atherosclerotic
      disease compared to healthy controls. (ii) Gene expression of IL-27 and IL-27R
      was significantly elevated in plaques compared to control vessels, and co
      localized to macrophages. (iii) In vitro, IL-27 increased NLRP3 inflammasome
      activation in monocytes with enhanced release of IL-1 beta. CONCLUSIONS: We
      demonstrate increased levels of IL-27 and IL-27R in patients with carotid
      atherosclerosis. Our in vitro findings suggest an inflammatory role for IL-27,
      which can possibly be linked to atherosclerotic disease development.

PMID- 29176765
TI  - Protection of mice deficient in mature B cells from West Nile virus infection by
      passive and active immunization.
AB  - B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in
      mature B cells, but unlike MUMT mice, they have normal numbers of newly formed,
      immature B cells. Using a West Nile virus (WNV) challenge model that requires
      antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR
      /- mice were highly susceptible to WNV and succumbed to infection within 8 to 12
      days after subcutaneous virus challenge. Although mature B cells were required to
      protect against lethal infection, infected BAFFR-/- mice had reduced WNV E
      specific IgG responses and neutralizing Abs. Passive transfer of immune sera from
      previously infected WT mice rescued BAFFR-/- and fully B cell-deficient MUMT
      mice, but unlike MUMT mice that died around 30 days post-infection, BAFFR-/- mice
      survived, developed WNV-specific IgG Abs and overcame a second WNV challenge.
      Remarkably, protective immunity could be induced in mature B cell-deficient mice.
      Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV
      infection induced Ab responses that protected against lethal infection in BAFFR-/
      mice but not in MUMT mice. Thus, the immature B cells present in BAFFR-/- and
      not MUMT mice contribute to protective antiviral immunity. A CD180-based vaccine
      may promote immunity in immunocompromised individuals.

PMID- 29176766
TI  - Establishment of an indirect ELISA for detection of the novel antifibrotic
      peptide M10.
AB  - OBJECTIVE: M10 is a ten amino acid peptide generated from the intracellular
      cytoplasmic tail of the hepatocyte growth factor (HGF) receptor c-Met following
      cleavage by caspase-3. Recently we reported that M10 interacts with Smad2 and
      demonstrates antifibrotic properties in vitro and in vivo and can be advanced
      into a novel antifibrotic remedy. The current study was undertaken to develop an
      immunoassay to measure M10 concentration in biological specimens. EXPERIMENTAL
      DESIGN: An Indirect Enzyme-Linked Immunosorbent Assay (ELISA) for detection of
      M10 in biological fluids was developed using pharmaceutical grade synthetic M10
      as a calibrator and commercially available anti-c-Met C12 antibody. RESULTS: M10
      ELISA specifically detected in plasma M10, but not a scrambled peptide, following
      a single intraperitoneal administration of M10 (1mg/kg) to mice. The detection
      limit was 9.6 ng/ml, and the measuring limit was between 15 ng/ml and 200 ng/ml.
      The recovery limits of M10 were between 80% and 120%; intra-assay coefficient of
      variation was between 5.3% and 6.3%; inter-assay coefficient of variation was
      between 5.0% and 8.0% over the buffer concentration tested in the range from 15
      ng /ml to 250 ng /ml. The peak of M10 concentration following a single
      intraperitoneal injection (1mg/kg) was achieved within 6 hours and declined to
      minimal levels by 48 hours. The experimentally obtained half-life for M10 was
      comparable to the theoretically predicted half-life for M10. CONCLUSIONS: We have
      established a highly sensitive ELISA to detect the antifibrotic peptide M10 in
      plasma samples, which should prove to be a novel tool to study the
      pharmacokinetics and efficacy of M10 in the treatment of fibroproliferative
      disorders.

PMID- 29176768
TI  - Employing open/hidden administration in psychotherapy research: A randomized
      controlled trial of expressive writing.
AB  - : Psychotherapy has been shown to be effective, but efforts to prove specific
      effects by placebo-controlled trials have been practically and conceptually
      hampered. We propose that adopting open/hidden designs from placebo research
      would offer a possible way to establish specificity in psychotherapy. Therefore,
      we tested the effects of providing opposing treatment rationales in an online
      expressive writing intervention on affect in healthy subjects. Results indicate
      that it was possible to conduct the expressive writing intervention both covertly
      and openly, but that participants in the hidden administration condition did not
      fully benefit from the otherwise effective expressive writing intervention in the
      long-run. Effect sizes between open and hidden administration groups were
      comparable to pre-post effect sizes of the intervention. While this finding is
      important for the understanding of psychotherapy's effects per se, it also proves
      that alternative research approaches to establish specificity are feasible and
      informative in psychotherapy research. TRIAL REGISTRATION: German Clinical Trials
      Register DRKS00009428.

PMID- 29176767
TI  - H1N1 influenza virus infection results in adverse pregnancy outcomes by
      disrupting tissue-specific hormonal regulation.
AB  - Increased susceptibility to influenza virus infection during pregnancy has been
      attributed to immunological changes occurring before and during gestation in
      order to "tolerate" the developing fetus. These systemic changes are most often
      characterized by a suppression of cell-mediated immunity and elevation of humoral
      immune responses referred to as the Th1-Th2 shift. However, the underlying
      mechanisms which increase pregnant mothers' risk following influenza virus
      infection have not been fully elucidated. We used pregnant BALB/c mice during mid
      to late gestation to determine the impact of a sub-lethal infection with
      A/Brisbane/59/07 H1N1 seasonal influenza virus on completion of gestation.
      Maternal and fetal health status was closely monitored and compared to infected
      non-pregnant mice. Severity of infection during pregnancy was correlated with
      premature rupture of amniotic membranes (PROM), fetal survival and body weight at
      birth, lung viral load and degree of systemic and tissue inflammation mediated by
      innate and adaptive immune responses. Here we report that influenza virus
      infection resulted in dysregulation of inflammatory responses that led to pre
      term labor, impairment of fetal growth, increased fetal mortality and maternal
      morbidity. We observed significant compartment-specific immune responses
      correlated with changes in hormonal synthesis and regulation. Dysregulation of
      progesterone, COX-2, PGE2 and PGF2alpha expression in infected pregnant mice was
      accompanied by significant remodeling of placental architecture and upregulation
      of MMP-9 early after infection. Collectively these findings demonstrate the
      potential of a seasonal influenza virus to initiate a powerful pro-abortive
      mechanism with adverse outcomes in fetal health.

PMID- 29176769
TI  - Decreased prevalence of cancer in patients with multiple sclerosis: A case
      control study.
AB  - BACKGROUND: Studies of cancer prevalence have produced conflicting results
      concerning the relative risk of overall and specific sub-types of cancer in
      patients with multiple sclerosis (MS). Contemporary controls and information on
      tobacco use and alcohol consumption are generally missing from previous studies.
      OBJECTIVES: To evaluate lifetime cancer prevalence in a large cohort of MS
      patients relative to appropriate controls. METHODS: We conducted a case-control
      study, using a postal survey of a cohort of MS patients. Of the 1574
      questionnaires sent, 1107 could be used for statistical analysis. Data from 1568
      controls were prospectively collected using the same self-administered survey
      among consecutive out-patients in a single neurology department. Propensity
      scores matched on age, gender, and history of smoking and alcohol consumption
      were calculated. RESULTS: Among the MS patients, 7.32% had ever presented with a
      cancer, whereas 12,63% of the controls had, leading to a bootstrap matched odds
      ratio (OR) of 0.63; 95% CI 0.57-0.70. Although only exploratory, the use of DMT
      (immunomodulators or immunosupressants) did not appear to increase this risk (p =
      0.42). The disease course also did not affect cancer prevalence. CONCLUSION: MS
      was associated with a reduced overall cancer risk.

PMID- 29176771
TI  - Multiple factors contribute to reproductive isolation between two co-existing
      Habenaria species (Orchidaceae).
AB  - Reproductive isolation is a key feature that forms barriers to gene flow between
      distinct plants. In orchids, prezygotic reproductive isolation has been
      considered to be strong, because their associations with highly specific
      pollinators. In this study, the reproductive ecology and reproductive isolation
      of two sympatric Habenaria species, H. davidii and H. fordii, was investigated by
      floral phenology and morphology, hand-pollination experiments and visitor
      observation in southwest China. The two species were dependent on insects for
      pollination and completely self-compatible. A number of factors have been
      identified to limit gene flow between the two species and achieved full
      reproductive isolation. Ecogeographic isolation was a weak barrier. H. fordii and
      H. davidii had completely overlapped flowering periods, and floral morphology
      plays an important role in floral isolation. The two species shared the same
      hawkmoth pollinator, Cechenena lineosa, but the pollinaria of the two orchids
      were attached on different body parts of pollinators. Prezygotic isolation was
      not complete, but the interspecific pollination treatments of each species
      resulted in no seed sets, indicating that unlike many other orchid species, in
      which the postzygotic reproductive isolation is very weak or complete absence,
      the post-zygotic isolation strongly acted in the stage of seed production between
      two species. The results illustrate the reproductive isolation between two
      species involves multiple plant life-history stages and a variety of reproductive
      barriers can contribute to overall isolation.

PMID- 29176770
TI  - High Trypanosoma spp. diversity is maintained by bats and triatomines in Espirito
      Santo state, Brazil.
AB  - The aim of this study was to reevaluate the ecology of an area in the Atlantic
      Forest, southeast Brazil, where Chagas disease (CD) has been found to occur. In a
      previous study, immediately after the occurrence of a CD case, we did not observe
      any sylvatic small mammals or dogs with Trypanosoma cruzi cruzi infections, but
      Triatoma vitticeps presented high T. c. cruzi infection rates. In this study, we
      investigated bats together with non-volant mammals, dogs, and triatomines to
      explore other possible T. c. cruzi reservoirs/hosts in the area. Seventy-three
      non-volant mammals and 186 bats were captured at three sites within the Guarapari
      municipality, Espirito Santo state. Rio da Prata and Amarelos sites exhibited
      greater richness in terms of non-volant mammals and bats species, respectively.
      The marsupial Metachirus nudicaudatus, the rodent Trinomys paratus, and the bats
      Artibeus lituratus and Carollia perspicillata were the most frequently captured
      species. As determined by positive hemocultures, only two non-volant mammals were
      found to be infected by Trypanosoma species: Monodelphis americana, which was
      infected by T. cascavelli, T. dionisii and Trypanosoma sp., and Callithrix
      geoffroyi, which was infected by T. minasense. Bats presented T. c. cruzi TcI and
      TcIII/V, T. c. marinkellei, T. dionisii, T. rangeli B and D, and Trypanosoma sp.
      infections. Seven dogs were infected with T. cruzi based only on serological
      exams. The triatomines T. vitticeps and Panstrongylus geniculatus were found to
      be infected by trypanosomes via microscopy. According to molecular
      characterization, T. vitticeps specimens were infected with T. c. cruzi TcI,
      TcII, TcIII/V, and TcIV, T. c. marinkellei and T. dionisii. We observed high
      trypanosome diversity in a small and fragmented region of the Atlantic Forest.
      This diversity was primarily maintained by bats and T. vitticeps. Our findings
      show that the host specificity of the Trypanosoma genus should be thoroughly
      reviewed. In addition, our data show that CD cases can occur without an enzootic
      cycle near residential areas.

PMID- 29176772
TI  - Symphyseal fixation in open book injuries cannot fully compensate anterior SI
      joint injury-A biomechanical study in a two-leg alternating load model.
AB  - INTRODUCTION: In open book injuries type Tile B1.1 or B1.2 also classified as APC
      II (anteroposterior compression), it remains controversial, if a fixation of the
      anterior ring provides sufficient stability or a fixation of the posterior ring
      should be included. Therefore the relative motion at the sacroiliac joint was
      quantified in a two-leg alternating load biomechanical pelvis model in the
      intact, the injured and the restored pelvis. METHODS: Fresh-frozen intact (I)
      pelvises (n = 6) were subjected to a non-destructive cyclic test under sinosuidal
      axial two-leg alternating load with progressively increasing amplitude.
      Afterwards an open book injury (J) including the anterior ligament complex of the
      left sacroiliac joint, the sacrospinal and sacrotuberal ligaments (Tile B1.1) was
      created and the specimens were retested. Finally, the symphysis was stabilized
      with a modular fixation system (1-, 2- or 4-rod configuration) (R) and specimens
      were cyclically retested. Relative motion at the sacroiliac joint was captured at
      both sacroiliac joints by motion tracking system at two load levels of 170 N and
      340 N during all tests. RESULTS: Relative sacroiliac joint movements at both load
      levels were significantly higher in the J-state compared to the I-state,
      excluding superoinferior translational movement. With exception of the
      anteroposterior translational movement at 340N, the relative sacroiliac joint
      movements after each of the three reconstructions (1-, 2-, 4-rod fixation) were
      significantly smaller compared to the J-state and did not differ significantly to
      the I-state, but stayed above the values of the latter. Relative movements did
      not differ significantly in a direct comparison between the 1-rod, 2-rod and 4
      rod fixations. CONCLUSION: Symphyseal locked plating significantly reduces
      relative movement of the sacroiliac joint in open book injuries type Tile B1.1 or
      B1.2 (APC II) but cannot fully restore the situation of the intact sacroiliac
      joint.

PMID- 29176773
TI  - Reflectance, absorbance and transmittance spectra of bermudagrass and manilagrass
      turfgrass canopies.
AB  - Leaves act as a primary organ for the interception of solar radiation and their
      spatial arrangement determines how the plant canopy interacts with light. Many
      studies have been carried out on the penetration of radiation into crops however
      to date, few results are available on turfgrasses, mainly due to the difficulties
      of introducing sensors into the turf without disturbing the natural position of
      the leaves. In the present research two warm season turfgrasses, hybrid
      bermudagrass (Cynodon dactylon * transvaalensis) 'Patriot' and manilagrass
      (Zoysia matrella) 'Zeon', were studied. The aim was to describe their canopy
      architecture grown with minimal disturbance to the natural arrangement of the
      leaves and stems, and to determine the potential effects of canopy architecture
      on light penetration and reflectance. Radiometric measurements were carried out
      at eight different profile levels of turfgrasses that were up to 12 cm tall. A LI
      COR 1800 spectroradiometer with an optical fiber cable and a 7 mm diameter sensor
      was used. Measurements were carried out in the 390-1100 nm region at 5 nm
      intervals. The LAI value was higher for the manilagrass (9.0) than for the hybrid
      bermudagrass (5.6). The transmitted radiation was found to be closely dependent
      on downward cumulative LAI. Despite a more upright habit (mean insertion angle of
      22.4 degrees  +/-3.4), Zoysia matrella showed a higher NIR reflectance compared
      to Cdxt, which has a horizontal leaf arrangement (mean insertion angle 62.1
      degrees  +/- 9.6). The species studied showed substantial differences both in
      terms of phytometric characteristics and in the capacity to attenuate solar
      radiation.

PMID- 29176774
TI  - Epithelial rotation is preceded by planar symmetry breaking of actomyosin and
      protects epithelial tissue from cell deformations.
AB  - Symmetry breaking is involved in many developmental processes that form bodies
      and organs. One of them is the epithelial rotation of developing tubular and
      acinar organs. However, how epithelial cells move, how they break symmetry to
      define their common direction, and what function rotational epithelial motions
      have remains elusive. Here, we identify a dynamic actomyosin network that breaks
      symmetry at the basal surface of the Drosophila follicle epithelium of acinar
      like primitive organs, called egg chambers, and may represent a candidate force
      generation mechanism that underlies the unidirectional motion of this epithelial
      tissue. We provide evidence that the atypical cadherin Fat2, a key planar cell
      polarity regulator in Drosophila oogenesis, directs and orchestrates transmission
      of the intracellular actomyosin asymmetry cue onto a tissue plane in order to
      break planar actomyosin symmetry, facilitate epithelial rotation in the opposite
      direction, and direct the elongation of follicle cells. In contrast, loss of this
      rotational motion results in anisotropic non-muscle Myosin II pulses that are
      disorganized in plane and causes cell deformations in the epithelial tissue of
      Drosophila eggs. Our work demonstrates that atypical cadherins play an important
      role in the control of symmetry breaking of cellular mechanics in order to
      facilitate tissue motion and model epithelial tissue. We propose that their
      functions may be evolutionarily conserved in tubular/acinar vertebrate organs.

PMID- 29176775
TI  - Investigating dye performance and crosstalk in fluorescence enabled bioimaging
      using a model system.
AB  - Detailed imaging of biological structures, often smaller than the diffraction
      limit, is possible in fluorescence microscopy due to the molecular size and
      photophysical properties of fluorescent probes. Advances in hardware and multiple
      providers of high-end bioimaging makes comparing images between studies and
      between research groups very difficult. Therefore, we suggest a model system to
      benchmark instrumentation, methods and staining procedures. The system we
      introduce is based on doped zeolites in stained polyvinyl alcohol (PVA) films: a
      highly accessible model system which has the properties needed to act as a
      benchmark in bioimaging experiments. Rather than comparing molecular probes and
      imaging methods in complicated biological systems, we demonstrate that the model
      system can emulate this complexity and can be used to probe the effect of
      concentration, brightness, and cross-talk of fluorophores on the detected
      fluorescence signal. The described model system comprises of lanthanide (III) ion
      doped Linde Type A zeolites dispersed in a PVA film stained with fluorophores. We
      tested: F18, MitoTracker Red and ATTO647N. This model system allowed comparing
      performance of the fluorophores in experimental conditions. Importantly, we here
      report considerable cross-talk of the dyes when exchanging excitation and
      emission settings. Additionally, bleaching was quantified. The proposed model
      makes it possible to test and benchmark staining procedures before these dyes are
      applied to more complex biological systems.

PMID- 29176776
TI  - Understanding heart rate alarm adjustment in the intensive care units through an
      analytical approach.
AB  - BACKGROUND: Heart rate (HR) alarms are prevalent in ICU, and these parameters are
      configurable. Not much is known about nursing behavior associated with tailoring
      HR alarm parameters to individual patients to reduce clinical alarm fatigue.
      OBJECTIVES: To understand the relationship between heart rate (HR) alarms and
      adjustments to reduce unnecessary heart rate alarms. METHODS: Retrospective,
      quantitative analysis of an adjudicated database using analytical approaches to
      understand behaviors surrounding parameter HR alarm adjustments. Patients were
      sampled from five adult ICUs (77 beds) over one month at a quaternary care
      university medical center. A total of 337 of 461 ICU patients had HR alarms with
      53.7% male, mean age 60.3 years, and 39% non-Caucasian. Default HR alarm
      parameters were 50 and 130 beats per minute (bpm). The occurrence of each alarm,
      vital signs, and physiologic waveforms was stored in a relational database (SQL
      server). RESULTS: There were 23,624 HR alarms for analysis, with 65.4% exceeding
      the upper heart rate limit. Only 51% of patients with HR alarms had parameters
      adjusted, with a median upper limit change of +5 bpm and -1 bpm lower limit. The
      median time to first HR parameter adjustment was 17.9 hours, without reduction in
      alarms occurrence (p = 0.57). CONCLUSIONS: HR alarms are prevalent in ICU, and
      half of HR alarm settings remain at default. There is a long delay between HR
      alarms and parameters changes, with insufficient changes to decrease HR alarms.
      Increasing frequency of HR alarms shortens the time to first adjustment. Best
      practice guidelines for HR alarm limits are needed to reduce alarm fatigue and
      improve monitoring precision.

PMID- 29176777
TI  - Risk of recurrence in chronic hepatitis B patients developing hepatocellular
      carcinoma with antiviral secondary prevention failure.
AB  - BACKGROUND: Nucleos(t)ide analogues (NUCs) treatment can reduce the risk of
      hepatocellular carcinoma (HCC) development and recurrence in chronic hepatitis B
      (CHB) patients. However, the risk of recurrence in CHB patients who develop HCC
      despite NUC treatment remains unclear. METHODS: 167 consecutive CHB patients
      receiving curative resection for HCC with NUC therapy after surgery were
      retrospectively enrolled. Thirty-eight patients who developed HCC despite NUC
      therapy for more than 1 year were defined as secondary prevention failure. The
      other 129 patients started NUC therapy after surgery. Factors associated with
      recurrence-free survival (RFS) and overall survival (OS) were evaluated. RESULTS:
      The 5-year RFS and OS rates were 44.7% and 77.3%, respectively. Sex, BMI, BCLC
      stage, AFP levels and cirrhosis status were the independent predictors of RFS,
      while microvascular invasion was the independent predictor of OS. The RFS was
      comparable between patients with and without NUC secondary prevention. In the
      subgroup analysis, the RFS was significantly worse in cirrhotic patients with
      secondary prevention failure (hazard ratio = 2.373, p = 0.009). Secondary
      prevention failure did not have adverse impact on OS. Among 84 patients with
      recurrence, 58.3% of the cases remained in BCLC stage A, and 53.6% received a
      second curative treatment. Long-term NUC therapy may lead to a decline of non
      invasive indices of hepatic fibrosis in HCC patients. CONCLUSIONS: In general,
      the risk of recurrence and survival are comparable between patients with and
      without secondary prevention failure. However, a higher risk of recurrence was
      observed in cirrhotic patients with secondary prevention failure.

PMID- 29176778
TI  - Cross-sectional interview study of fertility, pregnancy, and urogenital
      schistosomiasis in coastal Kenya: Documented treatment in childhood is associated
      with reduced odds of subfertility among adult women.
AB  - BACKGROUND: Previous research has documented an increased risk of subfertility in
      areas of sub-Saharan Africa, as well as an ecological association between
      urogenital schistosomiasis prevalence and decreased fertility. This pilot project
      examined reproductive patterns and the potential effects of childhood urogenital
      Schistosoma haematobium infection and individual treatment experience on adult
      subfertility among women who were long-term residents in an S. haematobium
      endemic region of coastal Kenya. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed
      findings from 162 in-depth interviews with women of childbearing age in a rural,
      coastal community, linking them, if possible, to their individual treatment
      records from previous multi-year longitudinal studies of parasitic infections.
      Reproductive histories indicated a much local higher local rate of subfertility
      (44%) than worldwide averages (8-12%). Although, due to the very high regional
      prevalence of schistosomiasis, a clear relationship could not be demonstrated
      between a history of S. haematobium infection and adult subfertility, among a
      convenience sub-sample of 61 women who had received documented treatment during
      previous interventional trials, a significant association was found between age
      at first anti-schistosomal treatment and later fertility in adulthood, with those
      women treated before age 21 significantly less likely to have subfertility (P =
      0.001). CONCLUSIONS/SIGNIFICANCE: The high subfertility rate documented in this
      pilot study suggests the importance of programs to prevent and treat pelvic
      infections in their early stages to preclude reproductive tract damage. The
      available documented treatment data also suggest that early anti-schistosomal
      treatment may prevent the fertility-damaging effects of urogenital
      schistosomiasis, and lend support for programs that provide universal treatment
      of children in S. haematobium-endemic regions.

PMID- 29176779
TI  - Maternal-Fetal rejection reactions are unconstrained in preeclamptic women.
AB  - The risk factors for preeclampsia, extremes of maternal age, changing paternity,
      concomitant maternal autoimmunity, and/or birth intervals greater than 5 years,
      suggest an underlying immunopathology. We used peripheral blood and lymphocytes
      from the UteroPlacental Interface (UPI) of 3rd trimester healthy pregnant women
      in multicolor flow cytometry-and in vitro suppression assays. The major end-point
      was the characterization of activation markers, and potential effector functions
      of different CD4-and CD8 subsets as well as T regulatory cells (Treg). We
      observed a significant shift of peripheral CD4 -and CD8- T cells from naive to
      memory phenotype in preeclamptic women compared to healthy pregnant women
      consistent with long-standing immune activation. While the proportions of the
      highly suppressive Cytokine and Activated Treg were increased in preeclampsia,
      Treg tolerance toward fetal antigens was dysfunctional. Thus, our observations
      indicate a long-standing inflammatory derangement driving immune activation in
      preeclampsia; in how far the Treg dysfunction is caused by/causes this immune
      activation in preeclampsia will be the object of future studies.

PMID- 29176780
TI  - Robust iterative closest point algorithm based on global reference point for
      rotation invariant registration.
AB  - The iterative closest point (ICP) algorithm is efficient and accurate for rigid
      registration but it needs the good initial parameters. It is easily failed when
      the rotation angle between two point sets is large. To deal with this problem, a
      new objective function is proposed by introducing a rotation invariant feature
      based on the Euclidean distance between each point and a global reference point,
      where the global reference point is a rotation invariant. After that, this
      optimization problem is solved by a variant of ICP algorithm, which is an
      iterative method. Firstly, the accurate correspondence is established by using
      the weighted rotation invariant feature distance and position distance together.
      Secondly, the rigid transformation is solved by the singular value decomposition
      method. Thirdly, the weight is adjusted to control the relative contribution of
      the positions and features. Finally this new algorithm accomplishes the
      registration by a coarse-to-fine way whatever the initial rotation angle is,
      which is demonstrated to converge monotonically. The experimental results
      validate that the proposed algorithm is more accurate and robust compared with
      the original ICP algorithm.

PMID- 29176781
TI  - 1HNMR-Based metabolomic profiling method to develop plasma biomarkers for
      sensitivity to chronic heat stress in growing pigs.
AB  - The negative impact of heat stress (HS) on the production performances in pig
      faming is of particular concern. Novel diagnostic methods are needed to predict
      the robustness of pigs to HS. Our study aimed to assess the reliability of blood
      metabolome to predict the sensitivity to chronic HS of 10 F1 (Large White *
      Creole) sire families (SF) reared in temperate (TEMP) and in tropical (TROP)
      regions (n = 56+/-5 offsprings/region/SF). Live body weight (BW) and rectal
      temperature (RT) were recorded at 23 weeks of age. Average daily feed intake
      (AFDI) and average daily gain were calculated from weeks 11 to 23 of age,
      together with feed conversion ratio. Plasma blood metabolome profiles were
      obtained by Nuclear Magnetic Resonance spectroscopy (1HNMR) from blood samples
      collected at week 23 in TEMP. The sensitivity to hot climatic conditions of each
      SF was estimated by computing a composite index of sensitivity (Isens) derived
      from a linear combination of t statistics applied to familial BW, ADFI and RT in
      TEMP and TROP climates. A model of prediction of sensitivity was established with
      sparse Partial Least Square Discriminant Analysis (sPLS-DA) between the two most
      robust SF (n = 102) and the two most sensitive ones (n = 121) using individual
      metabolomic profiles measured in TEMP. The sPLS-DA selected 29 buckets that
      enabled 78% of prediction accuracy by cross-validation. On the basis of this
      training, we predicted the proportion of sensitive pigs within the 6 remaining
      families (n = 337). This proportion was defined as the predicted membership of
      families to the sensitive category. The positive correlation between this
      proportion and Isens (r = 0.97, P < 0.01) suggests that plasma metabolome can be
      used to predict the sensitivity of pigs to hot climate.

PMID- 29176782
TI  - A universal mammalian vaccine cell line substrate.
AB  - Using genome-wide small interfering RNA (siRNA) screens for poliovirus, influenza
      A virus and rotavirus, we validated the top 6 gene hits PV, RV or IAV to search
      for host genes that when knocked-down (KD) enhanced virus permissiveness and
      replication over wild type Vero cells or HEp-2 cells. The enhanced virus
      replication was tested for 12 viruses and ranged from 2-fold to >1000-fold. There
      were variations in virus-specific replication (strain differences) across the
      cell lines examined. Some host genes (CNTD2, COQ9, GCGR, NDUFA9, NEU2, PYCR1,
      SEC16G, SVOPL, ZFYVE9, and ZNF205) showed that KD resulted in enhanced virus
      replication. These findings advance platform-enabling vaccine technology, the
      creation of diagnostic cells substrates, and are informative about the host
      mechanisms that affect virus replication in mammalian cells.

PMID- 29176783
TI  - Association of parathyroid hormone and vitamin D with untreated hypertension: Is
      it different in white-coat or sustained hypertension?
AB  - BACKGROUND: Previous reports about the relationship between a high parathyroid
      hormone (PTH) and low vitamin D levels with blood pressure in different
      hypertension groups are conflicting. OBJECTIVE: We studied serum PTH and vitamin
      D levels in white-coat (WCHT) and sustained hypertension (SHT) patients who had
      not been on antihypertensive treatment. We also investigated the association
      between serum PTH and vitamin D levels with respect to blood pressure in SHT and
      WCHT patients. METHODS: We included 52 SHT patients (54.06 +/- 9.2 years, 32
      newly diagnosed and 20 previously diagnosed with SHT who had not been treated
      with antihypertensive medication for 3 months or more), 48 WCHT patients (53.64
      +/- 9.5 years), and 50 normotensive (NT) healthy controls (53.44 +/- 8.4 years)
      in our study. In addition to routine tests, PTH and vitamin D levels were
      measured. RESULTS: Serum PTH levels were significantly higher in SHT patients not
      taking antihypertensive medications than in WCHT patients and NT controls (p =
      0.004). Although PTH levels were higher in WCHT than in NT groups, the difference
      was not statistically significant. In SHT patients, PTH levels showed a positive
      correlation with office systolic (r = 0.363, p = 0.008), office diastolic (r =
      0.282, p = 0.038), home systolic (r = 0.390, p = 0.004), and home diastolic blood
      pressures (r = 0.397, p = 0.003). Serum vitamin D levels were similar in SHT,
      WCHT and NT groups. Vitamin D levels were not associated with blood pressures in
      the entire study group. Furthermore, no significant relation was found between
      vitamin D and PTH levels in SHT and WCHT groups. CONCLUSION: PTH levels are
      significantly higher in untreated SHT patients than WCHT patients and NT
      subjects. However, vitamin D levels are similar in SHT, WCHT and NT groups. There
      is a significant association between PTH levels and blood pressures suggesting
      PTH has a role in increase of blood pressure in SHT.

PMID- 29176785
TI  - Association between polymorphisms of heat-shock protein 70 genes and noise
      induced hearing loss: A meta-analysis.
AB  - BACKGROUND: Recent studies have evaluated the associations between polymorphisms
      of the heat-shock protein 70 (HSP70) encoding genes and noise-induced hearing
      loss (NIHL). However, the conclusions of these studies are conflicting. The
      objective of this meta-analysis was to clarify the association between all known
      polymorphisms of HSP70 genetic loci and susceptibility to NIHL, based on existing
      reports. METHODS: We conducted a meta-analysis of the association between Hsp70
      polymorphisms (rs1043618, rs1061581, rs2075800, rs2227956, and rs2763979) and
      NIHL risk in both Chinese and Caucasian males. All statistical analysis was done
      with was conducted using the "meta" package (version 4.6-0) of R version 3.3.2
      and RStudio version 1.0.44. Online databases were searched for eligible case
      control studies on February 13, 2017. The odds ratio (OR), 95% confidence
      interval (CI), and P value were calculated using Mantel-Haenszel statistics under
      a random- or fixed-effect model. RESULTS: A total of five studies, reported via
      four articles from online databases, were included in our meta-analysis. For
      rs1061581 (from three studies), a significant association was detected in the
      allele model, homozygote model, and dominant model (G versus A: OR (95% CI) =
      1.32(1.05-1.67), GG versus AA: OR (95% CI) = 1.93(1.1-3.36), GG + AG versus AA:
      OR (95% CI) = 1.45(1.05-2.02)), but not in the heterozygote model or the
      recessive model. For rs1043618 (from five studies), rs2075800 (from two studies),
      rs2227956 (from four studies), rs2763979 (from two studies), no significant
      association was found for any genetic model. After subgroup analyses by
      ethnicity, significant associations were observed for the allele model,
      heterozygote model, and dominant model for rs1061581 and any genetic model for
      rs2227956 in Caucasians. CONCLUSIONS: The rs1043618, rs2075800, and rs2763979
      polymorphisms were not found to be associated with susceptibility to NIHL;
      however, the rs1061581 and rs2227956 polymorphisms were significantly associated
      with NIHL in Caucasian males.

PMID- 29176784
TI  - PRM1 and KAR5 function in cell-cell fusion and karyogamy to drive distinct
      bisexual and unisexual cycles in the Cryptococcus pathogenic species complex.
AB  - Sexual reproduction is critical for successful evolution of eukaryotic organisms
      in adaptation to changing environments. In the opportunistic human fungal
      pathogens, the Cryptococcus pathogenic species complex, C. neoformans primarily
      undergoes bisexual reproduction, while C. deneoformans undergoes both unisexual
      and bisexual reproduction. During both unisexual and bisexual cycles, a common
      set of genetic circuits regulates a yeast-to-hyphal morphological transition,
      that produces either monokaryotic or dikaryotic hyphae. As such, both the
      unisexual and bisexual cycles can generate genotypic and phenotypic diversity de
      novo. Despite the similarities between these two cycles, genetic and
      morphological differences exist, such as the absence of an opposite mating-type
      partner and monokaryotic instead of dikaryotic hyphae during C. deneoformans
      unisexual cycle. To better understand the similarities and differences between
      these modes of sexual reproduction, we focused on two cellular processes involved
      in sexual reproduction: cell-cell fusion and karyogamy. We identified orthologs
      of the plasma membrane fusion protein Prm1 and the nuclear membrane fusion
      protein Kar5 in both Cryptococcus species, and demonstrated their conserved roles
      in cell fusion and karyogamy during C. deneoformans alpha-alpha unisexual
      reproduction and C. deneoformans and C. neoformans a-alpha bisexual reproduction.
      Notably, karyogamy occurs inside the basidum during bisexual reproduction in C.
      neoformans, but often occurs earlier following cell fusion during bisexual
      reproduction in C. deneoformans. Characterization of these two genes also showed
      that cell fusion is dispensable for solo unisexual reproduction in C.
      deneoformans. The blastospores produced along hyphae during C. deneoformans
      unisexual reproduction are diploid, suggesting that diploidization occurs early
      during hyphal development, possibly through either an endoreplication pathway or
      cell fusion-independent karyogamy events. Taken together, our findings suggest
      distinct mating mechanisms for unisexual and bisexual reproduction in
      Cryptococcus, exemplifying distinct evolutionary trajectories within this
      pathogenic species complex.

PMID- 29176786
TI  - In vivo imaging of palisades of Vogt in dry eye versus normal subjects using en
      face spectral-domain optical coherence tomography.
AB  - PURPOSE: To evaluate a possible clinical application of spectral-domain optical
      coherence tomography (SD-OCT) using en-face module for the imaging of the
      corneoscleral limbus in normal subjects and dry eye patients. PATIENTS AND
      METHODS: Seventy-six subjects were included in this study. Seventy eyes of 35
      consecutive patients with dry eye disease and 82 eyes of 41 healthy control
      subjects were investigated. All subjects were examined with the Avanti RTVue(r)
      anterior segment OCT. En-face OCT images of the corneoscleral limbus were
      acquired in four quadrants (inferior, superior, nasal and temporal) and then were
      analyzed semi-quantitatively according to whether or not palisades of Vogt (POV)
      were visible. En-face OCT images were then compared to in vivo confocal
      microscopy (IVCM) in eleven eyes of 7 healthy and dry eye patients. RESULTS: En
      face SD-OCT showed POV as a radially oriented network, located in superficial
      corneoscleral limbus, with a good correlation with IVCM features. It provided an
      easy and reproducible identification of POV without any special preparation or
      any direct contact, with a grading scale from 0 (no visualization) to 3 (high
      visualization). The POV were found predominantly in superior (P<0.001) and
      inferior (P<0.001) quadrants when compared to the nasal and temporal quadrants
      for all subjects examined. The visibility score decreased with age (P<0.001) and
      was lower in dry eye patients (P<0.01). In addition, the score decreased in
      accordance with the severity of dry eye disease (P<0.001). CONCLUSION: En-face SD
      OCT is a non-contact imaging technique that can be used to evaluate the POV, thus
      providing valuable information about differences in the limbal anatomy of dry eye
      patients as compared to healthy patients.

PMID- 29176787
TI  - Vaccine-elicited memory CD4+ T cell expansion is impaired in the lungs during
      tuberculosis.
AB  - Immunological memory is the key biological process that makes vaccines possible.
      Although tuberculosis vaccines elicit protective immunity in animals, few provide
      durable protection. To understand why protection is transient, we evaluated the
      ability of memory CD4+ T cells to expand, differentiate, and control
      Mycobacterium tuberculosis. Both naive and memory CD4+ T cells initially
      proliferated exponentially, and the accumulation of memory T cells in the lung
      correlated with early bacterial control. However, later during infection, memory
      CD4+ T cell proliferation was curtailed and no protection was observed. We show
      that memory CD4+ T cells are first activated in the LN and their recruitment to
      the lung attenuates bacterial growth. However, their interaction with Mtb
      infected macrophages does not promote continued proliferation. We conclude that a
      lack of sustained expansion by memory-derived T cells in the lung limits the
      durability of their protection, linking their slower expansion with transient
      protection in vaccinated mice.

PMID- 29176788
TI  - Preservation of three-dimensional spatial structure in the gut microbiome.
AB  - Preservation of three-dimensional structure in the gut is necessary in order to
      analyze the spatial organization of the gut microbiota and gut luminal contents.
      In this study, we evaluated preparation methods for mouse gut with the goal of
      preserving micron-scale spatial structure while performing fluorescence imaging
      assays. Our evaluation of embedding methods showed that commonly used media such
      as Tissue-Tek Optimal Cutting Temperature (OCT) compound, paraffin, and polyester
      waxes resulted in redistribution of luminal contents. By contrast, a hydrophilic
      methacrylate resin, Technovit H8100, preserved three-dimensional organization.
      Our mouse intestinal preparation protocol optimized using the Technovit H8100
      embedding method was compatible with microbial fluorescence in situ hybridization
      (FISH) and other labeling techniques, including immunostaining and staining with
      both wheat germ agglutinin (WGA) and 4', 6-diamidino-2-phenylindole (DAPI). Mucus
      could be visualized whether the sample was fixed with paraformaldehyde (PFA) or
      with Carnoy's fixative. The protocol optimized in this study enabled simultaneous
      visualization of micron-scale spatial patterns formed by microbial cells in the
      mouse intestines along with biogeographical landmarks such as host-derived mucus
      and food particles.

PMID- 29176789
TI  - Promising new vaccine candidates against Campylobacter in broilers.
AB  - Campylobacter is the leading cause of human bacterial gastroenteritis in the
      European Union. Birds represent the main reservoir of the bacteria, and human
      campylobacteriosis mainly occurs after consuming and/or handling poultry meat.
      Reducing avian intestinal Campylobacter loads should impact the incidence of
      human diseases. At the primary production level, several measures have been
      identified to reach this goal, including vaccination of poultry. Despite many
      studies, however, no efficient vaccine is currently available. We have recently
      identified new vaccine candidates using the reverse vaccinology strategy. This
      study assessed the in vivo immune and protective potential of six newly
      identified vaccine antigens. Among the candidates tested on Ross broiler
      chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1)
      significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g,
      with the concomitant development of a specific humoral immune response. In a
      second trial, cecal load reductions results were not statistically confirmed
      despite the induction of a strong immune response. These vaccine candidates need
      to be further investigated since they present promising features.

PMID- 29176790
TI  - Attention-deficit/hyperactivity disorder associated with KChIP1 rs1541665 in Kv
      channels accessory proteins.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is an early onset childhood
      neurodevelopmental disorder with high heritability. A number of genetic risk
      factors and environment factors have been implicated in the pathogenesis of ADHD.
      Genes encoding for subtypes of voltage-dependent K channels (Kv) and accessory
      proteins to these channels have been identified in genome-wide association
      studies (GWAS) of ADHD. We conducted a two-stage case-control study to
      investigate the associations between five key genes (KChIP4, KChIP1, DPP10, FHIT,
      and KCNC1) and the risk of developing ADHD. In the discovery stage comprising 256
      cases and 372 controls, KChIP1 rs1541665 and FHIT rs3772475 were identified; they
      were further genotyped in the validation stage containing 328cases and 431
      controls.KChIP1 rs1541665 showed significant association with a risk of ADHD at
      both stages, with CC vs TT odds ratio (OR) = 1.961, 95% confidence interval (CI)
      = 1.366-2.497, in combined analyses (P-FDR = 0.007). Moreover, we also found
      rs1541665 involvement in ADHD-I subtype (OR (95% CI) = 2.341(1.713, 3.282), and
      Hyperactive index score (P = 0.005) in combined samples.Intriguingly, gene
      environmental interactions analysis consistently revealed the potential
      interactionsof rs1541665 collaboratingwith maternal stress pregnancy (Pmul =
      0.021) and blood lead (Padd = 0.017) to modify ADHD risk. In conclusion, the
      current study provides evidence that genetic variants of Kv accessory proteins
      may contribute to the susceptibility of ADHD.Further studies with different
      ethnicitiesare warranted to produce definitive conclusions.

PMID- 29176791
TI  - The importance of thinking beyond the water-supply in cholera epidemics: A
      historical urban case-study.
AB  - BACKGROUND: Planning interventions to respond to cholera epidemics requires an
      understanding of the major transmission routes. Interrupting short-cycle
      (household, foodborne) transmission may require different approaches as compared
      long-cycle (environmentally-mediated/waterborne) transmission. However,
      differentiating the relative contribution of short- and long-cycle routes has
      remained difficult, and most cholera outbreak control efforts focus on
      interrupting long-cycle transmission. Here we use high-resolution epidemiological
      and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to
      explore the relative contribution of short- and long-cycle transmission routes
      during a major urban epidemic. METHODOLOGY/PRINCIPAL FINDINGS: We fit a spatially
      explicit time-series meta-population model to 6,552 physician-reported cholera
      cases from Copenhagen in 1853. We estimated the contribution of long-cycle
      waterborne transmission between neighborhoods using historical municipal water
      infrastructure data, fitting the force of infection from hydraulic flow, then
      comparing model performance. We found the epidemic was characterized by
      considerable transmission heterogeneity. Some neighborhoods acted as localized
      transmission hotspots, while other neighborhoods were less affected or important
      in driving the epidemic. We found little evidence to support long-cycle
      transmission between hydrologically-connected neighborhoods. Collectively, these
      findings suggest short-cycle transmission was significant.
      CONCLUSIONS/SIGNIFICANCE: Spatially targeted cholera interventions, such as
      reactive vaccination or sanitation/hygiene campaigns in hotspot neighborhoods,
      would likely have been more effective in this epidemic than control measures
      aimed at interrupting long-cycle transmission, such as improving municipal water
      quality. We recommend public health planners consider programs aimed at
      interrupting short-cycle transmission as essential tools in the cholera control
      arsenal.

PMID- 29176792
TI  - Genome-wide DNase hypersensitivity, and occupancy of RUNX2 and CTCF reveal a
      highly dynamic gene regulome during MC3T3 pre-osteoblast differentiation.
AB  - The ability to discover regulatory sequences that control bone-related genes
      during development has been greatly improved by massively parallel sequencing
      methodologies. To expand our understanding of cis-regulatory regions critical to
      the control of gene expression during osteoblastogenesis, we probed the presence
      of open chromatin states across the osteoblast genome using global DNase
      hypersensitivity (DHS) mapping. Our profiling of MC3T3 mouse pre-osteoblasts
      during differentiation has identified more than 224,000 unique DHS sites.
      Approximately 65% of these sites are dynamic during temporal stages of
      osteoblastogenesis, and a majority of them are located within non-promoter
      (intergenic and intronic) regions. Nearly half of all DHS sites (both
      constitutive and dynamic) overlap binding events of the bone-essential RUNX2
      and/or the chromatin-related CTCF transcription factors. This finding reinforces
      the role of these regulatory proteins as essential components of the bone gene
      regulome. We observe a reduction in chromatin accessibility throughout the genome
      between pre-osteoblast and early osteoblasts. Our analysis also defined a class
      of differentially expressed genes that harbor DHS peaks centered within 1 kb
      downstream of transcriptional end sites (TES). These DHSs at the 3'-flanks of
      genes exhibit dynamic changes during differentiation that may impact regulation
      of the osteoblast genome. Taken together, the distribution of DHS regions within
      non-promoter locations harboring osteoblast and chromatin related transcription
      factor binding motifs, reflect novel cis-regulatory requirements to support
      temporal gene expression in differentiating osteoblasts.

PMID- 29176793
TI  - Menstrual cycle characteristics of young females with occult primary ovarian
      insufficiency at initial diagnosis and one-year follow-up with serum amh level
      and antral follicle count.
AB  - Occult primary ovarian insufficiency (also known as incipient ovarian failure or
      diminished ovarian reserve) is defined as serum AMH level <=1.1ng/mL in women
      under age 30. Limited data is available regarding the prevalence of occult POI,
      the preceding menstrual characteristics and its natural course in otherwise
      healthy young females. We aimed in this prospective observational study to
      determine the prevalence of occult POI in young females (< age 30) screened with
      serum AMH measurement; and analyze the patterns of change in their menstruation
      at initial assessment and one-year follow-up in relation to the changes in
      ovarian reserve quantitatively assessed with AMH and AFC. 963 young female
      college students under age 30 voluntarily participated in this study. 43 of them
      (4.4%) were diagnosed with occult POI as their AMH levels were <= 1.1ng/mL.
      Thirty-eight (83.4%) of them have regular cycles and denied any menstrual
      irregularity in the last 12 months. This rate was not statistically different
      from 7.3% of those with AMH>1.1ng/mL who reported at least one abnormal menstrual
      cycle in the last year (p = 0.36). Cycle length was significantly shorter in
      females with AMH <= 1.1ng/mL compared to those with AMH>1.1ng/mL (25.1+/-3.2 vs.
      31.2+/-2.8 respectively, p<0.001). Karyotype, FMR-1 mutation analyses and auto
      antibody screening returned normal in all. At one-year follow-up AMH, AFC and
      mean cycle length were further reduced compared to their values at initial
      assessment. Now, a greater proportion of the participants with occult POI were
      menstruating regularly at every 21 days compared to the initial evaluation one
      year ago (39.5% vs. 13.9% respectively, p = 0.013). Twenty-five underwent oocyte
      cryopreservation. These findings underscore the importance of screening young
      females with AMH for possible occult POI. It also emphasizes that young females
      with critically diminished ovarian reserve may continue to menstruate regularly
      without any characteristic menstrual abnormality other than shortening of cycle
      length.

PMID- 29176794
TI  - Capillary refill time during fluid resuscitation in patients with sepsis-related
      hyperlactatemia at the emergency department is related to mortality.
AB  - INTRODUCTION: Acute circulatory dysfunction in patients with sepsis can evolve
      rapidly into a progressive stage associated with high mortality. Early
      recognition and adequate resuscitation could improve outcome. However, since the
      spectrum of clinical presentation is quite variable, signs of hypoperfusion are
      frequently unrecognized in patients just admitted to the emergency department
      (ED). Hyperlactatemia is considered a key parameter to disclose tissue hypoxia
      but it is not universally available and getting timely results can be challenging
      in low resource settings. In addition, non-hypoxic sources can be involved in
      hyperlactatemia, and a misinterpretation could lead to over-resuscitation in an
      unknown number of cases. Capillary refill time (CRT) is a marker of peripheral
      perfusion that worsens during circulatory failure. An abnormal CRT in septic
      shock patients after ICU-based resuscitation has been associated with poor
      outcome. The aim of this study was to determine the prevalence of abnormal CRT in
      patients with sepsis-related hyperlactatemia in the early phase after ED
      admission, and its relationship with outcome. METHODS: We performed a prospective
      observational study. Septic patients with hyperlactemia at ED admission subjected
      to an initial fluid resuscitation (FR) were included. CRT and other parameters
      were assessed before and after FR. CRT-normal or CRT-abnormal subgroups were
      defined according to the status of CRT following initial FR, and major outcomes
      were registered. RESULTS: Ninety-five hyperlactatemic septic patients were
      included. Thirty-one percent had abnormal CRT at ED arrival. After FR, 87
      patients exhibited normal CRT, and 8 an abnormal one. Patients with abnormal CRT
      had an increased risk of adverse outcomes (88% vs. 20% p<0.001; RR 4.4 [2.7
      7.4]), and hospital mortality (63% vs. 9% p<0.001; RR 6.7 [2.9-16]) as compared
      to those with normal CRT after FR. Specifically, CRT-normal patients required
      less frequently mechanical ventilation, renal replacement therapy, and ICU
      admission, and exhibited a lower hospital mortality. CONCLUSIONS: Hyperlactatemic
      sepsis patients with abnormal CRT after initial fluid resuscitation exhibit
      higher mortality and worse clinical outcomes than patients with normal CRT.

PMID- 29176795
TI  - The full transcription map of mouse papillomavirus type 1 (MmuPV1) in mouse wart
      tissues.
AB  - Mouse papillomavirus type 1 (MmuPV1) provides, for the first time, the
      opportunity to study infection and pathogenesis of papillomaviruses in the
      context of laboratory mice. In this report, we define the transcriptome of MmuPV1
      genome present in papillomas arising in experimentally infected mice using a
      combination of RNA-seq, PacBio Iso-seq, 5' RACE, 3' RACE, primer-walking RT-PCR,
      RNase protection, Northern blot and in situ hybridization analyses. We
      demonstrate that the MmuPV1 genome is transcribed unidirectionally from five
      major promoters (P) or transcription start sites (TSS) and polyadenylates its
      transcripts at two major polyadenylation (pA) sites. We designate the P7503, P360
      and P859 as "early" promoters because they give rise to transcripts mostly
      utilizing the polyadenylation signal at nt 3844 and therefore can only encode
      early genes, and P7107 and P533 as "late" promoters because they give rise to
      transcripts utilizing polyadenylation signals at either nt 3844 or nt 7047, the
      latter being able to encode late, capsid proteins. MmuPV1 genome contains five
      splice donor sites and three acceptor sites that produce thirty-six RNA isoforms
      deduced to express seven predicted early gene products (E6, E7, E1, E1^M1, E1^M2,
      E2 and E8^E2) and three predicted late gene products (E1^E4, L2 and L1). The
      majority of the viral early transcripts are spliced once from nt 757 to 3139,
      while viral late transcripts, which are predicted to encode L1, are spliced
      twice, first from nt 7243 to either nt 3139 (P7107) or nt 757 to 3139 (P533) and
      second from nt 3431 to nt 5372. Thirteen of these viral transcripts were
      detectable by Northern blot analysis, with the P533-derived late E1^E4
      transcripts being the most abundant. The late transcripts could be detected in
      highly differentiated keratinocytes of MmuPV1-infected tissues as early as ten
      days after MmuPV1 inoculation and correlated with detection of L1 protein and
      viral DNA amplification. In mature warts, detection of L1 was also found in more
      poorly differentiated cells, as previously reported. Subclinical infections were
      also observed. The comprehensive transcription map of MmuPV1 generated in this
      study provides further evidence that MmuPV1 is similar to high-risk cutaneous
      beta human papillomaviruses. The knowledge revealed will facilitate the use of
      MmuPV1 as an animal virus model for understanding of human papillomavirus gene
      expression, pathogenesis and immunology.

PMID- 29176796
TI  - Revisiting primary neural leprosy: Clinical, serological, molecular, and
      neurophysiological aspects.
AB  - BACKGROUND: Leprosy neuropathy is considered the most common peripheral
      neuropathy of infectious etiology worldwide, representing a public health
      problem. Clinical diagnosis of primary neural leprosy (PNL) is challenging, since
      no skin lesions are found and the slit skin smear bacilloscopy is negative.
      However, there are still controversial concepts regarding the primary-neural
      versus pure-neural leprosy definition, which will be explored by using multiple
      clinical-laboratory analyses in this study. METHODOLOGY/PRINCIPAL FINDINGS:
      Seventy patients diagnosed with primary neural leprosy from 2014 to 2016
      underwent clinical, laboratorial and neurophysiological evaluation. All patients
      presented an asymmetric neural impairment, with nerve thickening in 58.6%.
      Electroneuromyography showed a pattern of mononeuropathy in 51.4%. Positivity for
      ELISA anti-PGL1 was 52.9%, while the qPCR of slit skin smear was 78.6%. The qPCR
      of nerve biopsies was positive in 60.8%. Patients with multiple mononeuropathy
      patterns showed lower levels of anti-PGL-1 (p = 0.0006), and higher frequency of
      neural thickening (p = 0.0008) and sensory symptoms (p = 0.01) than those with
      mononeuropathy. CONCLUSIONS/SIGNIFICANCE: PNL is not a synonym of pure neural
      leprosy, as this condition may include a generalized immune response and also a
      skin involvement, documented by molecular findings. Immunological, molecular, and
      neurophysiological tools must be implemented for diagnosing primary neural
      leprosy to achieve effective treatment and reduction of its resultant
      disabilities that still represent a public health problem in several developing
      nations. Finally, we propose a algorithm and recommendations for the diagnosis of
      primary neural leprosy based on the combination of the three clinical
      laboratorial tools.

PMID- 29176797
TI  - Cytokines, hepatic cell profiling and cell interactions during bone marrow cell
      therapy for liver fibrosis in cholestatic mice.
AB  - Bone marrow cells (BMC) migrate to the injured liver after transplantation,
      contributing to regeneration through multiple pathways, but mechanisms involved
      are unclear. This work aimed to study BMC migration, characterize cytokine
      profile, cell populations and proliferation in mice with liver fibrosis
      transplanted with GFP+ BMC. Confocal microscopy analysis showed GFP+ BMC near
      regions expressing HGF and SDF-1 in the fibrotic liver. Impaired liver cell
      proliferation in fibrotic groups was restored after BMC transplantation.
      Regarding total cell populations, there was a significant reduction in CD68+
      cells and increased Ly6G+ cells in transplanted fibrotic group. BMC contributed
      to the total populations of CD144, CD11b and Ly6G cells in the fibrotic liver,
      related to an increment of anti-fibrotic cytokines (IL-10, IL-13, IFN-gamma and
      HGF) and reduction of pro-inflammatory cytokines (IL-17A and IL-6). Therefore,
      HGF and SDF-1 may represent important chemoattractants for transplanted BMC in
      the injured liver, where these cells can give rise to populations of extrahepatic
      macrophages, neutrophils and endothelial progenitor cells that can interact
      synergistically with other liver cells towards the modulation of an anti-fibrotic
      cytokine profile promoting the onset of liver regeneration.

PMID- 29176798
TI  - The scavenging chemokine receptor ACKR2 has a significant impact on acute
      mortality rate and early lesion development after traumatic brain injury.
AB  - The atypical chemokine receptor ACKR2 promotes resolution of acute inflammation
      by operating as a scavenger receptor for inflammatory CC chemokines in several
      experimental models of inflammatory disorders, however its role in the brain
      remains unclear. Based on our previous reports of increased expression of
      inflammatory chemokines and their corresponding receptors following traumatic
      brain injury (TBI), we hypothesised that ACKR2 modulates neuroinflammation
      following brain trauma and that its deletion exacerbates cellular inflammation
      and chemokine production. We demonstrate increased CCL2 and ACKR2 mRNA expression
      in post-mortem human brain, whereby ACKR2 mRNA levels correlated with later times
      post-TBI. This data is consistent with the transient upregulation of ACKR2
      observed in mouse brain after closed head injury (CHI). As compared to WT
      animals, ACKR2-/- mice showed a higher mortality rate after CHI, while the
      neurological outcome in surviving mice was similar. At day 1 post-injury, ACKR2-/
      mice displayed aggravated lesion volume and no differences in CCL2 expression
      and macrophage recruitment relative to WT mice. Reciprocal regulation of ACKR2
      and CCL2 expression was explored in cultured astrocytes, which are recognized as
      the major source of CCL2 and also express ACKR2. ACKR2 mRNA increased as early as
      2 hours after an inflammatory challenge in WT astrocytes. As expected, CCL2
      expression also dramatically increased at 4 hours in WT astrocytes but was
      significantly lower in ACKR2-/- astrocytes, possibly indicating a co-regulation
      of CCL2 and ACKR2 in these cells. Conversely, in vivo, CCL2 mRNA/protein levels
      were increased similarly in ACKR2-/- and WT brains at 4 and 12 hours after CHI,
      in line with the lack of differences in cerebral macrophage recruitment and
      neurological recovery. In conclusion, ACKR2 is induced after TBI and has a
      significant impact on mortality and lesion development acutely following CHI,
      while its role in chemokine expression, macrophage activation, brain pathology,
      and neurological recovery at later time-points is minor. Concordant to evidence
      in multiple sclerosis experimental models, our data corroborate a distinct role
      for ACKR2 in cerebral inflammatory processes compared to its reported functions
      in peripheral tissues.

PMID- 29176799
TI  - Dry eye, sleep quality, and mood status in glaucoma patients receiving
      prostaglandin monotherapy were comparable with those in non-glaucoma subjects.
AB  - PURPOSE: Prior studies suggested that glaucoma patients suffer worse dry eye and
      mood and sleep disorders than non-glaucoma subjects. Prostaglandin analogues are
      first-line therapy for glaucoma, inducing few instillation problems and
      sufficient pressure-reduction effects. This study compared dry eye, sleep
      quality, and mood status between glaucoma patients receiving prostaglandin
      monotherapy and non-glaucoma subjects. METHODS: This cross-sectional study
      evaluated 1520 patients (579 males and 941 females) for glaucoma status and dry
      eye-related symptoms (dryness, eye fatigue, photophobia, pain, blurring) and
      signs (Schirmer test, tear break-up time, corneal staining scores). Of the total
      cohort, 93 patients were also evaluated by Pittsburgh sleep quality index (PSQI)
      and hospital anxiety and depression score (HADS). Inclusion criteria were
      consecutive patients >= 51 years of age and best-corrected visual acuity >=
      20/25. Glaucoma patients included those treated with prostaglandin or a fixed
      combination including prostaglandin. Exclusion criteria were history of ocular
      surgery within one month. Data were analyzed using the chi-square or Mann-Whitney
      U tests, at 5% significance. RESULTS: There were no significant differences in
      dry eye-related signs and symptoms between the control (n = 1431, mean age of
      66.9 years) and glaucoma groups (n = 89, 67.9 years). The psychiatric sub
      analysis of the control (n = 61, 66.2 years) and glaucoma groups (n = 32, 67.3
      years) revealed mean scores of 5.02 +/- 3.10 and 5.16 +/- 3.46 for PSQI (normal
      range <= 5), 9.47 +/- 5.61 and 9.42 +/- 7.36 for HADS (normal range <= 10), 4.84
      +/- 3.22 and 4.71 +/- 3.45 for anxiety (normal range <= 5), and 4.63 +/- 3.05 and
      4.71 +/- 4.40 for depression (normal range <= 5), respectively, without
      statistical significance. CONCLUSIONS: Our results were comparable between
      glaucoma patients on prostaglandin monotherapy and non-glaucoma subjects for dry
      eye-related clinical manifestations, sleep quality, and mood status.

PMID- 29176800
TI  - Disentangling self-management goal setting and action planning: A scoping review.
AB  - INTRODUCTION: The ongoing rise in the numbers of chronically ill people
      necessitates efforts for effective self-management. Goal setting and action
      planning are frequently used, as they are thought to support patients in changing
      their behavior. However, it remains unclear how goal setting and action planning
      in the context of self-management are defined in the scientific literature. This
      study aimed to achieve a better understanding of the various definitions used.
      METHODS: A scoping review was conducted, searching PubMed, Cinahl, PsychINFO and
      Cochrane. Inclusion and exclusion criteria were formulated to ensure the focus on
      goal setting/action planning and self-management. The literature was updated to
      December 2015; data selection and charting was done by two reviewers. A
      qualitative content analysis approach was used. RESULTS: Out of 9115 retrieved
      articles, 58 met the inclusion criteria. We created an overview of goal setting
      phases that were applied (preparation, formulation of goals, formulation of
      action plan, coping planning and follow-up). Although the phases we found are in
      accordance with commonly known frameworks for goal setting, it was striking that
      the majority of studies (n = 39, 67%) did not include all phases. We also
      prepared an overview of components and strategies for each goal setting phase.
      Interestingly, few strategies were found for the communication between patients
      and professionals about goals/action plans. Most studies (n = 35, 60%) focused
      goal setting on one single disease and on a predefined lifestyle behavior; nearly
      half of the articles (n = 27, 47%) reported a theoretical framework. DISCUSSION:
      The results might provide practical support for developers of interventions.
      Moreover, our results might encourage professionals to become more aware of the
      phases of the goal setting process and of strategies emphasizing on patient
      reflection. However, more research might be useful to examine strategies to
      facilitate communication about goals/action plans. It might also be worthwhile to
      develop and evaluate goal setting/action planning strategies for people with
      different and multiple chronic conditions.

PMID- 29176801
TI  - Increasing vaccine production using pulsed ultrasound waves.
AB  - Vaccination is a safe and effective approach to prevent deadly diseases. To
      increase vaccine production, we propose that a mechanical stimulation can enhance
      protein production. In order to prove this hypothesis, Sf9 insect cells were used
      to evaluate the increase in the expression of a fusion protein from hepatitis B
      virus (HBV S1/S2). We discovered that the ultrasound stimulation at a frequency
      of 1.5 MHz, intensity of 60 mW/cm2, for a duration of 10 minutes per day
      increased HBV S1/S2 by 27%. We further derived a model for transport through a
      cell membrane under the effect of ultrasound waves, tested the key assumptions of
      the model through a molecular dynamics simulation package, NAMD (Nanoscale
      Molecular Dynamics program) and utilized CHARMM force field in a steered
      molecular dynamics environment. The results show that ultrasound waves can
      increase cell permeability, which, in turn, can enhance nutrient / waste exchange
      thus leading to enhanced vaccine production. This finding is very meaningful in
      either shortening vaccine production time, or increasing the yield of proteins
      for use as vaccines.

PMID- 29176802
TI  - Assessment of automated analysis of portable oximetry as a screening test for
      moderate-to-severe sleep apnea in patients with chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: The coexistence of obstructive sleep apnea syndrome (OSAS) and
      chronic obstructive pulmonary disease (COPD) leads to increased morbidity and
      mortality. The development of home-based screening tests is essential to expedite
      diagnosis. Nevertheless, there is still very limited evidence on the
      effectiveness of portable monitoring to diagnose OSAS in patients with pulmonary
      comorbidities. OBJECTIVE: To assess the influence of suffering from COPD in the
      performance of an oximetry-based screening test for moderate-to-severe OSAS, both
      in the hospital and at home. METHODS: A total of 407 patients showing moderate-to
      high clinical suspicion of OSAS were involved in the study. All subjects
      underwent (i) supervised portable oximetry simultaneously to in-hospital
      polysomnography (PSG) and (ii) unsupervised portable oximetry at home. A
      regression-based multilayer perceptron (MLP) artificial neural network (ANN) was
      trained to estimate the apnea-hypopnea index (AHI) from portable oximetry
      recordings. Two independent validation datasets were analyzed: COPD versus non
      COPD. RESULTS: The portable oximetry-based MLP ANN reached similar intra-class
      correlation coefficient (ICC) values between the estimated AHI and the actual AHI
      for the non-COPD and the COPD groups either in the hospital (non-COPD: 0.937,
      0.909-0.956 CI95%; COPD: 0.936, 0.899-0.960 CI95%) and at home (non-COPD: 0.731,
      0.631-0.808 CI95%; COPD: 0.788, 0.678-0.864 CI95%). Regarding the area under the
      receiver operating characteristics curve (AUC), no statistically significant
      differences (p >0.01) between COPD and non-COPD groups were found in both
      settings, particularly for severe OSAS (AHI >=30 events/h): 0.97 (0.92-0.99
      CI95%) non-COPD vs. 0.98 (0.92-1.0 CI95%) COPD in the hospital, and 0.87 (0.79
      0.92 CI95%) non-COPD vs. 0.86 (0.75-0.93 CI95%) COPD at home. CONCLUSION: The
      agreement and the diagnostic performance of the estimated AHI from automated
      analysis of portable oximetry were similar regardless of the presence of COPD
      both in-lab and at-home. Particularly, portable oximetry could be used as an
      abbreviated screening test for moderate-to-severe OSAS in patients with COPD.

PMID- 29176803
TI  - Root bark of Ulmus davidiana var. japonica restrains acute alcohol-induced
      hepatic steatosis onset in mice by inhibiting ROS accumulation.
AB  - Alcohol-induced hepatic steatosis and inflammation are key drivers of alcohol
      induced liver injury, mainly caused by oxidative stress. The roots bark of Ulmus
      davidiana var. japonica is well known for its substantial antioxidative and
      antitumorigenic potency. In this study, we examined whether this plant can
      ameliorate alcohol-induced liver injuries characterized by hepatic steatosis and
      inflammation through its antioxidative activity. C57BL/6J mice were treated with
      the root bark extract of Ulmus davidiana var. japonica (RUE; 100 mg of extract/kg
      bodyweight; oral gavage) and alcohol (1 g/kg of bodyweight; oral gavage) for 5
      days. Markers of acute alcohol-induced hepatic steatosis were determined and
      putative molecular mechanisms responsible for the protection of RUE were
      investigated. RUE noticeably protected against alcohol-induced hepatic steatosis
      and inflammation. Reactive oxygen species (ROS), over-produced by alcohol,
      negatively orchestrated various signaling pathways involved in the lipid
      metabolism and inflammation. These pathways were restored through the ROS
      scavenging activity of RUE in the liver. In particular, the expression of
      lipogenic genes (e.g., SREBP-1, ACC, and FAS) and inflammatory cytokines (e.g.,
      IL-1beta, and NF-kappaB p65) significantly decreased with RUE treatment.
      Conversely, the expression of fatty acid oxidation-related genes (e.g., SIRT1,
      AMPKalpha, and PGC1alpha) were increased in mice treated with RUE. Thus, the
      results indicate that RUE counteracts and thus attenuates alcoholic hepatic
      steatosis onset in mice, possibly by suppressing ROS-mediated steatosis and
      inflammation.

PMID- 29176804
TI  - One crisis, diverse impacts-Tissue-specificity of folate deficiency-induced
      circulation defects in zebrafish larvae.
AB  - Folate (vitamin B9) is an essential nutrient required for cell survival,
      proliferation, differentiation and therefore embryogenesis. Folate deficiency has
      been associated with many diseases, including congenital heart diseases and
      megaloblastic anemia, yet the mechanisms underlying these remains elusive. Here,
      we examine the impact of folate deficiency on the development of the circulation
      system using a zebrafish transgenic line which displays inducible folate
      deficiency. Impaired hematopoiesis includes decreased hemoglobin levels,
      decreased erythrocyte number, increased erythrocyte size and aberrant c-myb
      expression pattern were observed in folate deficient embryos. Cardiac defects,
      including smaller chamber size, aberrant cardiac function and cmlc2 expression
      pattern, were also apparent in folate deficient embryos. Characterization of
      intracellular folate content in folate deficiency revealed a differential
      fluctuation among the different folate derivatives that carry a single carbon
      group at different oxidation levels. Rescue attempts by folic acid and
      nucleotides resulted in differential responses among affected tissues, suggesting
      that different pathomechanisms are involved in folate deficiency-induced
      anomalies in a tissue-specific manner. The results of the current study provide
      an explanation for the inconsistent outcome observed clinically in patients
      suffering from folate deficiency and/or receiving folate supplementation. This
      study also supports the use of this model for further research on the defective
      cardiogenesis and hematopoiesis caused by folate deficiency.

PMID- 29176805
TI  - Modulation of host central carbon metabolism and in situ glucose uptake by
      intracellular Trypanosoma cruzi amastigotes.
AB  - Obligate intracellular pathogens satisfy their nutrient requirements by coupling
      to host metabolic processes, often modulating these pathways to facilitate access
      to key metabolites. Such metabolic dependencies represent potential targets for
      pathogen control, but remain largely uncharacterized for the intracellular
      protozoan parasite and causative agent of Chagas disease, Trypanosoma cruzi.
      Perturbations in host central carbon and energy metabolism have been reported in
      mammalian T. cruzi infection, with no information regarding the impact of host
      metabolic changes on the intracellular amastigote life stage. Here, we performed
      cell-based studies to elucidate the interplay between infection with
      intracellular T. cruzi amastigotes and host cellular energy metabolism. T. cruzi
      infection of non-phagocytic cells was characterized by increased glucose uptake
      into infected cells and increased mitochondrial respiration and mitochondrial
      biogenesis. While intracellular amastigote growth was unaffected by decreased
      host respiratory capacity, restriction of extracellular glucose impaired
      amastigote proliferation and sensitized parasites to further growth inhibition by
      2-deoxyglucose. These observations led us to consider whether intracellular T.
      cruzi amastigotes utilize glucose directly as a substrate to fuel metabolism.
      Consistent with this prediction, isolated T. cruzi amastigotes transport
      extracellular glucose with kinetics similar to trypomastigotes, with subsequent
      metabolism as demonstrated in 13C-glucose labeling and substrate utilization
      assays. Metabolic labeling of T. cruzi-infected cells further demonstrated the
      ability of intracellular parasites to access host hexose pools in situ. These
      findings are consistent with a model in which intracellular T. cruzi amastigotes
      capitalize on the host metabolic response to parasite infection, including the
      increase in glucose uptake, to fuel their own metabolism and replication in the
      host cytosol. Our findings enrich current views regarding available carbon
      sources for intracellular T. cruzi amastigotes and underscore the metabolic
      flexibility of this pathogen, a feature predicted to underlie successful
      colonization of tissues with distinct metabolic profiles in the mammalian host.

PMID- 29176806
TI  - Phylogeography of the Central American lancehead Bothrops asper (SERPENTES:
      VIPERIDAE).
AB  - The uplift and final connection of the Central American land bridge is considered
      the major event that allowed biotic exchange between vertebrate lineages of
      northern and southern origin in the New World. However, given the complex
      tectonics that shaped Middle America, there is still substantial controversy over
      details of this geographical reconnection, and its role in determining
      biogeographic patterns in the region. Here, we examine the phylogeography of
      Bothrops asper, a widely distributed pitviper in Middle America and northwestern
      South America, in an attempt to evaluate how the final Isthmian uplift and other
      biogeographical boundaries in the region influenced genealogical lineage
      divergence in this species. We examined sequence data from two mitochondrial
      genes (MT-CYB and MT-ND4) from 111 specimens of B. asper, representing 70
      localities throughout the species' distribution. We reconstructed phylogeographic
      patterns using maximum likelihood and Bayesian methods and estimated divergence
      time using the Bayesian relaxed clock method. Within the nominal species, an
      early split led to two divergent lineages of B. asper: one includes five
      phylogroups distributed in Caribbean Middle America and southwestern Ecuador, and
      the other comprises five other groups scattered in the Pacific slope of Isthmian
      Central America and northwestern South America. Our results provide evidence of a
      complex transition that involves at least two dispersal events into Middle
      America during the final closure of the Isthmus.

PMID- 29176807
TI  - Adolescent motherhood in Bangladesh: Trends and determinants.
AB  - BACKGROUND: While studies on fertility and contraceptives issues are available,
      until recently adolescent motherhood has not received enough attention among
      policy makers in understanding adolescent motherhood in Bangladesh. We aimed to
      examine the trends and determinants of adolescent motherhood among women aged 15
      49 years. METHODS: For trend analysis we used all the 7 waves of Bangladesh
      Demographic and Health Survey (BDHS, 1993-2014) data but for multivariate
      analysis 4 waves of BDHS (2004-2014). Two separate analyses were carried out on
      ever married women aged 15-49: (1) teenage girls aged 15-19 and (2) adult women
      aged 20 and above. RESULTS: The prevalence of adolescent motherhood had declined
      to a slower pace from 1993 to2014 (from 33.0% to 30.8%). Lower spousal age gap
      and higher education were found to be associated with lower likelihood of
      adolescent motherhood both among teenage girls [OR 0.447 (0.374-0.533)] and adult
      women [OR 0.451 (0.420-0.484)]. Teenage girls in the poorest wealth quintile [OR
      1.712 [1.350-2.173] were more likely to experience adolescent motherhood than the
      richest wealth quintile. Teenage girls who had no education were found to have
      2.76 times higher odds of adolescent motherhood than their counterparts who had
      higher than secondary education. Concerning the time effect, the odds of
      adolescent motherhood among adult women was found to decline overtime.
      CONCLUSIONS: Despite substantial decrease in total fertility rate in Bangladesh
      adolescent motherhood is still highly prevalent though declining from 1993 to
      2014. Social policies including those addressing poverty, ensuring greater
      emphasis on education for women; and adolescent mothers in rural areas are
      needed.

PMID- 29176808
TI  - Initial-state-dependent, robust, transient neural dynamics encode conscious
      visual perception.
AB  - Recent research has identified late-latency, long-lasting neural activity as a
      robust correlate of conscious perception. Yet, the dynamical nature of this
      activity is poorly understood, and the mechanisms governing its presence or
      absence and the associated conscious perception remain elusive. We applied
      dynamic-pattern analysis to whole-brain slow (< 5 Hz) cortical dynamics recorded
      by magnetoencephalography (MEG) in human subjects performing a threshold-level
      visual perception task. Up to 1 second before stimulus onset, brain activity
      pattern across widespread cortices significantly predicted whether a threshold
      level visual stimulus was later consciously perceived. This initial state of
      brain activity interacts nonlinearly with stimulus input to shape the evolving
      cortical activity trajectory, with seen and unseen trials following well
      separated trajectories. We observed that cortical activity trajectories during
      conscious perception are fast evolving and robust to small variations in the
      initial state. In addition, spontaneous brain activity pattern prior to stimulus
      onset also influences unconscious perceptual making in unseen trials. Together,
      these results suggest that brain dynamics underlying conscious visual perception
      belongs to the class of initial-state-dependent, robust, transient neural
      dynamics.

PMID- 29176809
TI  - Association between social support and health-related quality of life among
      Chinese seafarers: A cross-sectional study.
AB  - BACKGROUND: Seafarers have reported impaired health and health-related quality of
      life (HRQOL). Social support might increase HRQOL, but little is known about this
      association among Chinese seafarers. The aim of this study was to describe social
      support and explore its association with HRQOL among Chinese seafarers. METHODS:
      A cross-sectional survey was conducted in the ports of Nantong and Rugao, China,
      from April to December 2013. A total of 917 Chinese seafarers were interviewed on
      social support, mental distress, perceived occupational stress, and HRQOL using
      the following self-administered questionnaires: The Social Support Rating Scale,
      Self-rating Depression Scale, Occupational Stress Questionnaire, and the World
      Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire.
      Hierarchical linear regression modelling was used to analyze the association
      between seafarers' subjective level of social support and their HRQOL. RESULTS:
      Of the 917 male Chinese seafarers included in the study, 40.7% perceived high
      levels of social support, and 39.1% were highly satisfied with their overall
      quality of life (QOL). Hierarchical regression analysis showed significant
      associations between level of social support and all health dimensions in the
      WHOQOL-BREF, even after adjusting for depressive symptoms, occupational stress,
      occupational activities, sleep duration, and other relevant covariates. Compared
      with the medium or low level social support group, seafarers with a high level of
      social support had better QOL scores in the general facet health and QOL (beta =
      2.43, p<0.05), and the physical health (beta = 3.23, p<0.001), psychological
      health (beta = 5.56, p<0.001), social relation (beta = 6.07, p<0.001), and
      environment domains (beta = 4.27, p<0.001). In addition, depression, occupational
      stress, occupational activities, and sleep duration were found to be determinants
      of seafarers' HRQOL. CONCLUSIONS: Chinese seafarers have poorer HRQOL than the
      general population, but social support has a significant positive effect on their
      HRQOL. Efforts to improve social support should be undertaken.

PMID- 29176811
TI  - Dietary partitioning of Australia's two marsupial hypercarnivores, the Tasmanian
      devil and the spotted-tailed quoll, across their shared distributional range.
AB  - Australia's native marsupial fauna has just two primarily flesh-eating
      'hypercarnivores', the Tasmanian devil (Sarcophilus harrisii) and the spotted
      tailed quoll (Dasyurus maculatus) which coexist only on the island of Tasmania.
      Devil populations are currently declining due to a fatal transmissible cancer.
      Our aim was to analyse the diet of both species across their range in Tasmania,
      as a basis for understanding how devil decline might affect the abundance and
      distribution of quolls through release from competition. We used faecal analysis
      to describe diets of one or both species at 13 sites across Tasmania. We compared
      diet composition and breadth between the two species, and tested for geographic
      patterns in diets related to rainfall and devil population decline. Dietary items
      were classified into 6 broad categories: large mammals (>= 7.0kg), medium-sized
      mammals (0.5-6.9kg), small mammals (< 0.5kg), birds, reptiles and invertebrates.
      Diet overlap based on prey-size category was high. Quoll diets were broader than
      devils at all but one site. Devils consumed more large and medium-sized mammals
      and quolls more small mammals, reptiles and invertebrates. Medium-sized mammals
      (mainly Tasmanian pademelon Thylogale billardierii), followed by large mammals
      (mainly Bennett's wallaby Macropus rufogriseus) and birds, were the most
      important prey groups for both species. Diet composition varied across sites,
      suggesting that both species are flexible and opportunistic foragers, but was not
      related to rainfall for devils. Quolls included more large mammals but fewer
      small mammals and invertebrates in their diet in the eastern drier parts of
      Tasmania where devils have declined. This suggests that a competitive release of
      quolls may have occurred and the substantial decline of devils has provided more
      food in the large-mammal category for quolls, perhaps as increased scavenging
      opportunities. The high diet overlap suggests that if resources become limited in
      areas of high devil density, interspecific competition could occur.

PMID- 29176810
TI  - Flip/flop mating-type switching in the methylotrophic yeast Ogataea polymorpha is
      regulated by an Efg1-Rme1-Ste12 pathway.
AB  - In haploid cells of Ogataea (Hansenula) polymorpha an environmental signal,
      nitrogen starvation, induces a reversible change in the structure of a
      chromosome. This process, mating-type switching, inverts a 19-kb DNA region to
      place either MATa or MATalpha genes under centromeric repression of
      transcription, depending on the orientation of the region. Here, we investigated
      the genetic pathway that controls switching. We characterized the transcriptomes
      of haploid and diploid O. polymorpha by RNAseq in rich and nitrogen-deficient
      media, and found that there are no constitutively a-specific or alpha-specific
      genes other than the MAT genes themselves. We mapped a switching defect in a
      sibling species (O. parapolymorpha strain DL-1) by interspecies bulk segregant
      analysis to a frameshift in the transcription factor EFG1, which in Candida
      albicans regulates filamentous growth and white-opaque switching. Gene knockout,
      overexpression and ChIPseq experiments show that EFG1 regulates RME1, which in
      turn regulates STE12, to achieve mating-type switching. All three genes are
      necessary both for switching and for mating. Overexpression of RME1 or STE12 is
      sufficient to induce switching without a nitrogen depletion signal. The
      homologous recombination genes RAD51 and RAD17 are also necessary for switching.
      The pathway controlling switching in O. polymorpha shares no components with the
      regulation of HO in S. cerevisiae, which does not involve any environmental
      signal, but it shares some components with mating-type switching in Kluyveromyces
      lactis and with white-opaque phenotypic switching in C. albicans.

PMID- 29176812
TI  - Generation Y and surgical residency - Passing the baton or the end of the world
      as we know it? Results from a survey among medical students in Germany.
AB  - INTRODUCTION: The current student generation have their own expectations toward
      professional life and pay particular attention to their work-life balance. Less
      interest in work-intensive specialties leads to a shortage of skilled candidates
      especially in surgery. In order to motivate students into a surgical residency,
      new priorities become important. A deeper understanding of the underlying
      arguments and students' expectations towards a surgical training are necessary to
      counteract a future shortage of specialized surgeons. METHODS: We conducted an
      internet-based survey among medical students at two representative German
      university hospitals to gain more information about the underlying mechanisms
      that lead to opting for and against a surgical career. We particularly paid
      attention to gender differences and differences between students of different
      academic years. RESULTS: A total of 1098 students participated in the survey.
      Sixty-four percent were female. The majority of the students were of the opinion
      that surgery is an interesting and meaningful profession. In contrast, when it
      comes to their own career choice, most students (89% female and 81% male) are not
      willing to choose a surgical specialty. While students are certainly willing to
      spend a large amount of time on their professional lives, at the same time they
      demand planning reliability and a sufficient work-life balance. Flexibility in
      working hours and an existing childcare program were identified as predominant
      factors for all students and in particular for female students. The same applies
      to a respectful conversional tone and appreciation of the individual work.
      Factors like prestige and salary were less relevant than "self-fulfillment" in
      terms of respectful interaction and balancing their working and private lives.
      There was significant difference in female and male students as female students
      have clearer ideas concerning career planning but at the same time are less self
      confident than their male colleagues. Moreover, there was a significant
      difference between junior and senior students regarding career planning with a
      shift to less work-intensive specialties and especially away from a surgical
      residency in older students. Adjustments to working hours models, working
      environment, clinical curriculum and a respectful interaction are factors that
      might increase the willingness of young students to choose a surgical career.

PMID- 29176813
TI  - In situ organism-sediment interactions: Bioturbation and biogeochemistry in a
      highly depositional estuary.
AB  - Organic matter (OM) production and degradation is important in coastal estuaries,
      and OM fate is strongly influenced by the coupled interactions of bioturbation
      and biogeochemistry. From April to September 2013 sediment cores and a benthic
      observing system, Wormcam, were used to investigate the in situ relationship of
      biogeochemistry and macrofauna bioturbation in Cape Lookout Bight North Carolina.
      Wormcam imagery provided a vivid depiction of macrofauna functioning in an
      environment not previously observed, and affirmed the importance of fine-scale
      temporal observations of the benthic environment in situ. Observation of
      macrofauna presence and bioturbation during the summer contradicted previous
      studies that found this area to be azoic during methane activity and sulfide
      build-up. Sulfate concentrations decreased while sulfide and dissolved inorganic
      carbon concentrations increased during the summer. This coincided with changes in
      the depth and rates of bioturbation. Summer burrow depths (~0.8 cm) and rates
      (~0.4 cm h-1) were significantly less than spring burrow depths (~3.0 cm) and
      rates (~1.0 cm h-1). While sulfate reduction and OM degradation increased with
      temperature at a microscopic level, macroscopic OM degradation was reduced. As a
      result, reduced conditions dominated and a thin aerobic sediment layer, a few
      millimeters in thickness, was visible at the sediment surface. Decreases in
      macrofauna burrow depth and rates diminishes the area of influence of
      bioturbators, limiting bioturbation and subsequently the important ecosystem
      functions these organisms provide.

PMID- 29176814
TI  - Correction: Detection of atypical network development patterns in children with
      autism spectrum disorder using magnetoencephalography.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184422.].

PMID- 29176815
TI  - Growth, ammonium metabolism, and photosynthetic properties of Ulva australis
      (Chlorophyta) under decreasing pH and ammonium enrichment.
AB  - The responses of macroalgae to ocean acidification could be altered by
      availability of macronutrients, such as ammonium (NH4+). This study determined
      how the opportunistic macroalga, Ulva australis responded to simultaneous changes
      in decreasing pH and NH4+ enrichment. This was investigated in a week-long growth
      experiment across a range of predicted future pHs with ambient and enriched NH4+
      treatments followed by measurements of relative growth rates (RGR), NH4+ uptake
      rates and pools, total chlorophyll, and tissue carbon and nitrogen content. Rapid
      light curves (RLCs) were used to measure the maximum relative electron transport
      rate (rETRmax) and maximum quantum yield of photosystem II (PSII) photochemistry
      (Fv/Fm). Photosynthetic capacity was derived from the RLCs and included the
      efficiency of light harvesting (alpha), slope of photoinhibition (beta), and the
      light saturation point (Ek). The results showed that NH4+ enrichment did not
      modify the effects of pH on RGRs, NH4+ uptake rates and pools, total chlorophyll,
      rETRmax, alpha, beta, Fv/Fm, tissue C and N, and the C:N ratio. However, Ek was
      differentially affected by pH under different NH4+ treatments. Ek increased with
      decreasing pH in the ambient NH4+ treatment, but not in the enriched NH4+
      treatment. NH4+ enrichment increased RGRs, NH4+ pools, total chlorophyll,
      rETRmax, alpha, beta, Fv/Fm, and tissue N, and decreased NH4+ uptake rates and
      the C:N ratio. Decreased pH increased total chlorophyll content, rETRmax, Fv/Fm,
      and tissue N content, and decreased the C:N ratio. Therefore, the results
      indicate that U. australis growth is increased with NH4+ enrichment and not with
      decreasing pH. While decreasing pH influenced the carbon and nitrogen metabolisms
      of U. australis, it did not result in changes in growth.

PMID- 29176816
TI  - A large outbreak of Hepatitis E virus genotype 1 infection in an urban setting in
      Chad likely linked to household level transmission factors, 2016-2017.
AB  - BACKGROUND: In September 2016, three acutely jaundiced (AJS) pregnant women were
      admitted to Am Timan Hospital, eastern Chad. We described the outbreak and
      conducted a case test-negative study to identify risk factors for this genotype
      of HEV in an acute outbreak setting. METHODS: Active case finding using a
      community based surveillance network identified suspected AJS cases. Pregnant or
      visibly ill AJS cases presenting at hospital were tested with Assure(r) IgM HEV
      rapid diagnostic tests (RDTs) and some with Polymerase Chain Reaction (PCR) in
      Amsterdam; confirmed cases were RDT-positive and controls were RDT-negative. All
      answered questions around: demographics, household makeup, area of residence,
      handwashing practices, water collection behaviour and clinical presentation. We
      calculated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CI).
      RESULTS: Between September and April 2017, 1443 AJS cases (1293 confirmed) were
      detected in the town(attack rate: 2%; estimated 65,000 population). PCR testing
      confirmed HEV genotype 1e. HEV RDTs were used for 250 AJS cases; 100 (40%) were
      confirmed. Risk factors for HEV infection, included: having at least two children
      under the age of 5 years (OR 2.1, 95%CI 1.1-4.3), having another household member
      with jaundice (OR 2.4, 95%CI 0.90-6.3) and, with borderline significance, living
      in the neighbourhoods of Riad (OR 3.8, 95%CI 1.0-1.8) or Ridina (OR 3.3, 95%CI
      1.0-12.6). Cases were more likely to present with vomiting (OR 3.2, 9%CI 1.4-7.9)
      than controls; possibly due to selection bias. Cases were non-significantly less
      likely to report always washing hands before meals compared with controls (OR
      0.33, 95%CI 0.1-1.1). DISCUSSION: Our study suggests household factors and area
      of residence (possibly linked to access to water and sanitation) play a role in
      HEV transmission; which could inform future outbreak responses. Ongoing sero
      prevalence studies will elucidate more aspects of transmission dynamics of this
      virus with genotype 1e.

PMID- 29176818
TI  - Effects of the Blob on settlement of spotted sand bass, Paralabrax
      maculatofasciatus, to Mission Bay, San Diego, CA.
AB  - The West Coast of the United States experienced variable and sometimes highly
      unusual oceanographic conditions between 2012 and 2015. In particular, a warm
      mass of surface water known as the Pacific Warm Anomaly (popularly as "The Blob")
      impinged on southern California in 2014, and warm-water conditions remained
      during the 2015 El Nino. We examine how this oceanographic variability affected
      delivery and individual characteristics of larval spotted sand bass (Paralabrax
      maculatofasciatus) to an estuarine nursery habitat in southern California. To
      quantify P. maculatofasciatus settlement patterns, three larval collectors were
      installed near the mouth of Mission Bay, San Diego CA, and retrieved weekly from
      June-October of 2012-2015. During 'Blob' conditions in 2014 and 2015, lower
      settlement rates of spotted sand bass were associated with higher sea surface
      temperature and lower wind speed, chlorophyll a (chl a) and upwelling. Overall,
      the number of settlers per day peaked at intermediate chl a values across weeks.
      Individual characteristics of larvae that settled in 2014-2015 were consistent
      with a poor feeding environment. Although settlers were longer in length in 2014
      15, fish in these years had slower larval otolith growth, a longer larval
      duration, and a trend towards lower condition, traits that are often associated
      with lower survival and recruitment. This study suggests that future settlement
      and recruitment of P. maculatofasciatus and other fishes with similar life
      histories may be adversely affected in southern California if ocean temperatures
      continue to rise in the face of climate change.

PMID- 29176817
TI  - Individual and community factors contributing to anemia among women in rural Baja
      California, Mexico.
AB  - INTRODUCTION: Anemia is a public health concern among women in rural Baja
      California, Mexico. The purpose of this study was to identify the individual and
      community factors contributing to the disproportionately high prevalence of
      anemia among women in this region. METHODS: A cross-sectional study of 118 women
      (15-49 years) was performed in a rural colonia (small settlement) in Baja
      California, Mexico in 2012. Participants completed a survey comprised of
      demographic, socioeconomic, health, and dietary questions and provided a
      capillary blood sample. A portable HemoCue was used to measure hemoglobin and
      diagnose anemia. Anemic participants provided a venous blood sample for
      laboratory testing to elucidate the etiology of anemia. Anemic participants
      received vitamin supplements and nutritional counseling. Assessments of six local
      tiendas (community grocery stores) were performed to ascertain the types of food
      available for purchase within the community. RESULTS: Prevalence of anemia was
      22% among women; laboratory tests revealed iron deficiency was the primary
      etiology in 80.8% of anemia cases. Other causes of anemia in women included
      vitamin B-12 deficiency (11.5%) and combined iron and vitamin B-12 deficiency
      (7.7%). Women from low SES households and women enrolled in the government
      assistance program Prospera were significantly more likely to be anemic (OR =
      3.48, 95% CI 1.35-8.98 and OR = 2.49, 95% CI 1.02-6.09, respectively). Vitamin
      supplementation was significantly more common among non-anemic women (OR = 0.12,
      95% CI 0.02-0.94). Dietary assessments showed limited consumption of iron
      absorption enhancing foods such as fruits and vegetables. Assessments of local
      tiendas revealed at least one type of meat and citrus fruit available for
      purchase at each store; however, leafy green vegetables were only available for
      purchase at one store. CONCLUSION: All cases of anemia were due to nutritional
      deficiencies. While vitamin supplementation is a temporary solution, improved
      individual nutrition knowledge and community access to iron absorption enhancing
      foods, particularly produce, is needed. Promoting government assistance programs
      like Prospera and implementing additional programs designed to improve nutrition
      and health literacy, in conjunction with ensuring access to nutritious foods,
      might reduce the high prevalence nutritional anemia within the community.

PMID- 29176819
TI  - Metabolism drives distribution and abundance in extremophile fish.
AB  - Differences in population density between species of varying size are frequently
      attributed to metabolic rates which are assumed to scale with body size with a
      slope of 0.75. This assumption is often criticised on the grounds that 0.75
      scaling of metabolic rate with body size is not universal and can vary
      significantly depending on species and life-history. However, few studies have
      investigated how interspecific variation in metabolic scaling relationships
      affects population density in different sized species. Here we predict inter
      specific differences in metabolism from niche requirements, thereby allowing
      metabolic predictions of species distribution and abundance at fine spatial
      scales. Due to the differences in energetic efficiency required along harsh
      benign gradients, an extremophile fish (brown mudfish, Neochanna apoda) living in
      harsh environments had slower metabolism, and thus higher population densities,
      compared to a fish species (banded kokopu, Galaxias fasciatus) in physiologically
      more benign habitats. Interspecific differences in the intercepts for the
      relationship between body and density disappeared when species mass-specific
      metabolic rates, rather than body sizes, were used to predict density, implying
      population energy use was equivalent between mudfish and kokopu. Nevertheless,
      despite significant interspecific differences in the slope of the metabolic
      scaling relationships, mudfish and kokopu had a common slope for the relationship
      between body size and population density. These results support underlying logic
      of energetic equivalence between different size species implicit in metabolic
      theory. However, the precise slope of metabolic scaling relationships, which is
      the subject of much debate, may not be a reliable indicator of population density
      as expected under metabolic theory.

PMID- 29176820
TI  - Genome-wide association study for grain yield and related traits in elite wheat
      varieties and advanced lines using SNP markers.
AB  - Genetic improvement of grain yield is always an important objective in wheat
      breeding. Here, a genome-wide association study was conducted to parse the
      complex genetic composition of yield-related traits of 105 elite wheat varieties
      (lines) using the Wheat 90K Illumina iSelect SNP array. Nine yield-related
      traits, including maximum number of shoots per square meter (MSN), effective
      number of spikes per square meter (ESN), percentage of effective spike (PES),
      number of kernels per spike (KPS), thousand-kernel weight (TKW), the ratio of
      kernel length/kernel width (RLW), leaf-area index (LAI), plant height (PH), and
      grain yield (GY), were evaluated across four environments. Twenty four highly
      significant marker-trait associations (MTAs) (P < 0.001) were identified for nine
      yield-related traits on chromosomes 1A, 1D, 2A (2), 3B, 4A (2), 4B, 5A (4), 5B
      (4), 5D, 6B (2), 7A (2), and 7B (3), explaining 10.86-20.27% of the phenotypic
      variations. Of these, four major loci were identified in more than three
      environments, including one locus for RLW (6B), one locus for TKW (7A), and two
      loci for PH (7B). A cleaved amplified polymorphic sequence (CAPS) marker Td99211
      for TKW on chromosome 5A was developed and validated in both a natural population
      composed of 372 wheat varieties (lines) and a RIL population derived from the
      cross of Yangxiaomai * Zhongyou 9507. The CAPS marker developed can be directly
      used for marker-assisted selection in wheat breeding, and the major MTAs
      identified can provide useful information for fine-mapping of the target genes in
      future studies.

PMID- 29176821
TI  - Familial transmission of a body-related attentional bias - An eye-tracking study
      in a nonclinical sample of female adolescents and their mothers.
AB  - BACKGROUND: Previous research indicates that body image disturbance is
      transmitted from mother to daughter via modeling of maternal body-related
      behaviors and attitudes (indirect transmission) and via maternal body-related
      feedback (direct transmission). So far, the transmission of body-related
      attentional biases, which according to cognitive-behavioral theories play a
      prominent role in the development and maintenance of eating disorders, has not
      been analyzed. The current eye-tracking study applied the concepts of direct and
      indirect transmission to body-related attentional biases by examining body
      related viewing patterns on self- and other-pictures within mother-daughter
      dyads. METHODS: Eye movements of N = 82 participants (n = 41 healthy female
      adolescents, mean age 15.82 years, SD = 1.80, and their mothers, mean age 47.78
      years, SD = 4.52) were recorded while looking at whole-body pictures of
      themselves and a control peer. Based on fixations on self-defined attractive and
      unattractive body areas, visual attention bias scores were calculated for mothers
      and daughters, representing the pattern of body-related attention allocation.
      Based on mothers' fixations on their own daughter's and the adolescent peer's
      body, a second visual attention bias score was calculated, reflecting the
      mothers' viewing pattern on their own daughter. RESULTS: Analysis of variance
      revealed an attentional bias for self-defined unattractive body areas in
      adolescents. The girls' visual attention bias score correlated significantly with
      their mothers' bias score, indicating indirect transmission, and with their
      mothers' second bias score, indicating direct transmission. Moreover, the girls'
      bias score correlated significantly with negative body-related feedback from
      their mothers. CONCLUSIONS: Female adolescents show a deficit-oriented
      attentional bias for one's own and a peer's body. The correlated body-related
      attention patterns imply that attentional biases might be transmitted directly
      and indirectly from mothers to daughters. Results underline the potential
      relevance of maternal influences for the development of body image disturbance in
      girls and suggest specific family-based approaches for the prevention and
      treatment of eating disorders.

PMID- 29176822
TI  - Change detection in pictorial and solid scenes: The role of depth of field.
AB  - This paper investigates the influence of depth of field on change detection in
      both pictorial and solid scenes. In this work, a within-subjects experiment is
      conducted using a flicker paradigm, with which the hit rate and response time for
      change detection are obtained. The results show that depth of field has effects
      on change detection: the hit rate is smaller and response time is longer in the
      scene with small depth of field than in the scene with large depth of field or
      uniform blur. It is concluded that when depth of field is small and binocular
      disparity is not zero in a picture, the influence of depth of field on change
      detection is more significant than binocular disparity. This conclusion leads to
      the result that the change in the sharp area is detected easier and faster than
      in the area that is closer to the observer.

PMID- 29176823
TI  - Vitamin D receptor is present on the neuronal plasma membrane and is co-localized
      with amyloid precursor protein, ADAM10 or Nicastrin.
AB  - Our recent study indicated that vitamin D and its receptors are important parts
      of the amyloid processing pathway in neurons. Yet the role of vitamin D receptor
      (VDR) in amyloid pathogenesis is complex and all regulations over the production
      of amyloid beta cannot be explained solely with the transcriptional regulatory
      properties of VDR. Given that we hypothesized that VDR might exist on the
      neuronal plasma membrane in close proximity with amyloid precursor protein (APP)
      and secretase complexes. The present study primarily focused on the localization
      of VDR in neurons and its interaction with amyloid pathology-related proteins.
      The localization of VDR on neuronal membranes and its co-localization with target
      proteins were investigated with cell surface staining followed by
      immunofluorescence labelling. The FpClass was used for protein-protein
      interaction prediction. Our results demonstrated the localization of VDR on the
      neuronal plasma membrane and the co-localization of VDR and APP or ADAM10 or
      Nicastrin and limited co-localization of VDR and PS1. E-cadherin interaction with
      APP or the gamma-secretase complex may involve NOTCH1, NUMB, or FHL2, according
      to FpClass. This suggested complex might also include VDR, which greatly
      contributes to Ca+2 hemostasis with its ligand vitamin D. Consequently, we
      suggested that VDR might be a member of this complex also with its own non
      genomic action and that it can regulate the APP processing pathway in this way in
      neurons.

PMID- 29176825
TI  - The effect of spatial randomness on the average fixation time of mutants.
AB  - The mean conditional fixation time of a mutant is an important measure of
      stochastic population dynamics, widely studied in ecology and evolution. Here, we
      investigate the effect of spatial randomness on the mean conditional fixation
      time of mutants in a constant population of cells, N. Specifically, we assume
      that fitness values of wild type cells and mutants at different locations come
      from given probability distributions and do not change in time. We study spatial
      arrangements of cells on regular graphs with different degrees, from the circle
      to the complete graph, and vary assumptions on the fitness probability
      distributions. Some examples include: identical probability distributions for
      wild types and mutants; cases when only one of the cell types has random fitness
      values while the other has deterministic fitness; and cases where the mutants are
      advantaged or disadvantaged. Using analytical calculations and stochastic
      numerical simulations, we find that randomness has a strong impact on fixation
      time. In the case of complete graphs, randomness accelerates mutant fixation for
      all population sizes, and in the case of circular graphs, randomness delays
      mutant fixation for N larger than a threshold value (for small values of N,
      different behaviors are observed depending on the fitness distribution
      functions). These results emphasize fundamental differences in population
      dynamics under different assumptions on cell connectedness. They are explained by
      the existence of randomly occurring "dead zones" that can significantly delay
      fixation on networks with low connectivity; and by the existence of randomly
      occurring "lucky zones" that can facilitate fixation on networks of high
      connectivity. Results for death-birth and birth-death formulations of the Moran
      process, as well as for the (haploid) Wright Fisher model are presented.

PMID- 29176826
TI  - Aggregate-level lead exposure, gun violence, homicide, and rape.
AB  - CONTEXT: An increasing body of research has linked the geographic distribution of
      lead with various indicators of criminal and antisocial behavior. OBJECTIVE: The
      current study, using data from an ongoing project related to lead exposure in St.
      Louis City, MO, analyzed the association between aggregate blood lead levels and
      specific indicators violent crime within the city. DESIGN: Ecological study.
      SETTING: St. Louis, Missouri. EXPOSURE MEASURE: Blood lead levels. MAIN OUTCOME
      MEASURE: Official reports of violent crimes were categorized as 1) crimes
      involving a firearm (yes/no), 2) assault crimes (with or without a firearm), 3)
      robbery crimes (with or without a firearm), 4) homicides and 5) rape. RESULTS:
      With the exception of rape, aggregate blood-lead levels were statistically
      significant predictors of violent crime at the census tract level. The risk
      ratios for each of the outcome measures were as follows: firearm crimes 1.03
      (1.03-1.04), assault crimes 1.03 (1.02-1.03), robbery crimes 1.03 (1.02-1.04),
      homicide 1.03 (1.01, 1.04), and rape 1.01 (0.99-1.03). CONCLUSIONS: Extending
      prior research in St. Louis, results suggest that aggregated lead exposure at the
      census tract level predicted crime outcomes, even after accounting for important
      sociological variables. Moving forward, a more developed understanding of
      aggregate level crime may necessitate a shift toward studying the synergy between
      sociological and biological risk factors such as lead exposure.

PMID- 29176824
TI  - Safety and efficacy of a freeze-dried trivalent antivenom for snakebites in the
      Brazilian Amazon: An open randomized controlled phase IIb clinical trial.
AB  - BACKGROUND: In tropical areas, a major concern regarding snakebites treatment
      effectiveness relates to the failure in liquid antivenom (AV) distribution due to
      the lack of an adequate cold chain in remote areas. To minimize this problem,
      freeze-drying has been suggested to improve AV stability. METHODS AND FINDINGS:
      This study compares the safety and efficacy of a freeze-dried trivalent antivenom
      (FDTAV) and the standard liquid AV provided by the Brazilian Ministry of Health
      (SLAV) to treat Bothrops, Lachesis and Crotalus snakebites. This was a
      prospective, randomized, open, phase IIb trial, carried out from June 2005 to May
      2008 in the Brazilian Amazon. Primary efficacy endpoints were the suppression of
      clinical manifestations and return of hemostasis and renal function markers to
      normal ranges within the first 24 hours of follow-up. Primary safety endpoint was
      the presence of early adverse reactions (EAR) in the first 24 hours after
      treatment. FDTAV thermal stability was determined by estimating AV potency over
      one year at 56 degrees C. Of the patients recruited, 65 and 51 were assigned to
      FDTAV and SLAV groups, respectively. Only mild EARs were reported, and they were
      not different between groups. There were no differences in fibrinogen (p = 0.911)
      and clotting time (p = 0.982) recovery between FDTAV and SLAV treated groups for
      Bothrops snakebites. For Lachesis and Crotalus snakebites, coagulation parameters
      and creatine phosphokinase presented normal values 24 hours after AV therapy for
      both antivenoms. CONCLUSIONS/SIGNIFICANCE: Since promising results were observed
      for efficacy, safety and thermal stability, our results indicate that FDTAV is
      suitable for a larger phase III trial. TRIAL REGISTRATION: ISRCTNregistry:
      ISRCTN12845255; DOI: 10.1186/ISRCTN12845255
      (http://www.isrctn.com/ISRCTN12845255).

PMID- 29176827
TI  - Who is more likely to be obese or overweight among siblings? A nationally
      representative study in rural China.
AB  - BACKGROUND: The aims of this study were to determine the association between
      sibling rank and childhood obesity among children <= 5 years of age in rural
      China, and to investigate the effect of child gender and the obesity status of
      other siblings on this association. METHODS: Data from the China Family Panel
      Studies, a nationally representative survey, was used for the analysis. Sibling
      rank was defined as the birth order of all children with the same biological
      mother. A total of 1116 children <= 5 years of age were divided into four groups:
      children without siblings, first-born children, second-born children, and third
      born or younger children. For each child, the body mass index and standard
      deviation (BMI z score) was calculated according to WHO standards; children with
      BMI z scores > 2 were classified as obese or overweight (ObOw). Logistic
      regression models were used to estimate the association between sibling rank and
      ObOw status, and the possible influence of gender and ObOw status among other
      siblings. RESULTS: The second and third-born or younger children had a
      significantly higher risk of becoming ObOw than children without siblings (odds
      ratio [OR]: 1.32, 95% confidence interval [CI]: 1.07-1.63 and OR:1.38, 95% CI:
      1.17-1.63, respectively). Specifically, female second-born children and male
      third-born or younger children had a significantly higher risk of ObOw (OR: 1.50,
      95% CI: 1.11-2.01 and OR: 1.57, 95% CI: 1.07-2.32, respectively). Having an ObOw
      sibling increased the probability of being ObOw and the magnitude of the effect
      was larger if siblings were younger. CONCLUSIONS: Sibling rank was shown to be
      associated with ObOw status among children 0-5 years of age in rural China. Our
      findings can help healthcare practitioners and authorities to identify children
      at risk of obesity. Future studies should focus on the mechanisms of this
      association.

PMID- 29176829
TI  - Tobacco industry attempts to frame smoking as a 'disability' under the 1990
      Americans with Disabilities Act.
AB  - Using the Truth Tobacco Industry Documents Library and Congressional records, we
      examined the tobacco industry's involvement with the 1990 Americans with
      Disabilities Act (ADA). During legislative drafting of the ADA (1989-1990), the
      Tobacco Institute, the tobacco industry's lobbying and public relations arm at
      the time, worked with industry lawyers and civil rights groups to include smoking
      in the ADA's definition of "disability." Focus was on smoking as a perceived
      rather than actual disability so that tobacco companies could maintain that
      smoking is not addictive. Language that would have explicitly excluded smoking
      from ADA coverage was weakened or omitted. Tobacco Institute lawyers did not
      think the argument that smokers are "disabled" would convince the courts, so in
      the two years after the ADA was signed into law, the Tobacco Institute paid a
      lawyer to conduct media tours, seminars, and write articles to convince employers
      that hiring only non-smokers would violate the ADA. The ultimate goal of these
      activities was to deter employers from promoting a healthy, tobacco-free
      workforce and, more broadly, to promote the social acceptability of smoking.
      Employers and policy makers need to be aware that tobacco use is not protected by
      the ADA and should not be misled by tobacco industry efforts to insinuate
      otherwise.

PMID- 29176828
TI  - T cell recognition of Mycobacterium tuberculosis peptides presented by HLA-E
      derived from infected human cells.
AB  - HLA-E is a non-conventional MHC Class I molecule that has been recently
      demonstrated to present pathogen-derived ligands, resulting in the TCR-dependent
      activation of alphabeta CD8+ T cells. The goal of this study was to characterize
      the ligandome displayed by HLA-E following infection with Mycobacterium
      tuberculosis (Mtb) using an in-depth mass spectrometry approach. Here we
      identified 28 Mtb ligands derived from 13 different source proteins, including
      the Esx family of proteins. When tested for activity with CD8+ T cells isolated
      from sixteen donors, nine of the ligands elicited an IFN-gamma response from at
      least one donor, with fourteen of 16 donors responding to the Rv0634A19-29
      peptide. Further evaluation of this immunodominant peptide response confirmed HLA
      E restriction and the presence of Rv0634A19-29-reactive CD8+ T cells in the
      peripheral blood of human donors. The identification of an Mtb HLA-E ligand that
      is commonly recognized may provide a target for a non-traditional vaccine
      strategy.

PMID- 29176830
TI  - The effect of dam construction on the movement of dwarf caimans, Paleosuchus
      trigonatus and Paleosuchus palpebrosus, in Brazilian Amazonia.
AB  - Run-of-the-river hydroelectric dams cause changes in seasonal inundation of the
      floodplains, and this may cause displacement of semi-aquatic vertebrates present
      before dam construction. This study evaluated the movement of crocodilians before
      and after the filling of the Santo Antonio hydroelectric reservoir on the Madeira
      River in the Brazilian Amazon, which occurred in November 2011. We radio-tracked
      four adult male Paleosuchus palpebrosus and four adult male Paleosuchus
      trigonatus before and after the formation of the reservoir between 2011 and 2013.
      The home ranges of the P. palpebrosus varied from < 1 km2 to 91 km2 and the home
      ranges of the P. trigonatus varied from < 1km2 to 5 km2. The species responded
      differently to time since filling and water level in weekly movement and home
      range. However, overall the dam appears to have had little effect on the use of
      space by the individuals that were present before dam construction.

PMID- 29176832
TI  - A user exposure based approach for non-structural road network vulnerability
      analysis.
AB  - Aiming at the dense urban road network vulnerability without structural negative
      consequences, this paper proposes a novel non-structural road network
      vulnerability analysis framework. Three aspects of the framework are mainly
      described: (i) the rationality of non-structural road network vulnerability, (ii)
      the metrics for negative consequences accounting for variant road conditions, and
      (iii) the introduction of a new vulnerability index based on user exposure. Based
      on the proposed methodology, a case study in the Sioux Falls network which was
      usually threatened by regular heavy snow during wintertime is detailedly
      discussed. The vulnerability ranking of links of Sioux Falls network with respect
      to heavy snow scenario is identified. As a result of non-structural consequences
      accompanied by conceivable degeneration of network, there are significant
      increases in generalized travel time costs which are measurements for
      "emotionally hurt" of topological road network.

PMID- 29176831
TI  - SAGA mediates transcription from the TATA-like element independently of
      Taf1p/TFIID but dependent on core promoter structures in Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae, core promoters of class II genes contain a TATA
      element, either a TATA box (TATA[A/T]A[A/T][A/G]) or TATA-like element (1 or 2 bp
      mismatched version of the TATA box). The TATA element directs the assembly of the
      preinitiation complex (PIC) to ensure accurate transcriptional initiation. It has
      been proposed the PIC is assembled by two distinct pathways in which TBP is
      delivered by TFIID or SAGA, leading to the widely accepted model that these
      complexes mediate transcription mainly from TATA-like element- or TATA box
      containing promoters, respectively. Although both complexes are involved in
      transcription of nearly all class II genes, it remains unclear how efficiently
      SAGA mediates transcription from TATA-like element-containing promoters
      independently of TFIID. We found that transcription from the TATA box-containing
      AGP1 promoter was greatly stimulated in a Spt3p-dependent manner after
      inactivation of Taf1p/TFIID. Thus, this promoter provides a novel experimental
      system in which to evaluate SAGA-mediated transcription from TATA-like
      element(s). We quantitatively measured transcription from various TATA-like
      elements in the Taf1p-dependent CYC1 promoter and Taf1p-independent AGP1
      promoter. The results revealed that SAGA could mediate transcription from at
      least some TATA-like elements independently of Taf1p/TFIID, and that Taf1p
      dependence or -independence is highly robust with respect to variation of the
      TATA sequence. Furthermore, chimeric promoter mapping revealed that Taf1p
      dependence or independence was conferred by the upstream activating sequence
      (UAS), whereas Spt3p-dependent transcriptional stimulation after inactivation of
      Taf1p/TFIID was specific to the AGP1 promoter and dependent on core promoter
      regions other than the TATA box. These results suggest that TFIID and/or SAGA are
      regulated in two steps: the UAS first specifies TFIID or SAGA as the predominant
      factor on a given promoter, and then the core promoter structure guides the
      pertinent factor to conduct transcription in an appropriate manner.

PMID- 29176833
TI  - Characterization of small-to-medium head-and-face dimensions for developing
      respirator fit test panels and evaluating fit of filtering facepiece respirators
      with different faceseal design.
AB  - A respirator fit test panel (RFTP) with facial size distribution representative
      of intended users is essential to the evaluation of respirator fit for new models
      of respirators. In this study an anthropometric survey was conducted among youths
      representing respirator users in mid-Taiwan to characterize head-and-face
      dimensions key to RFTPs for application to small-to-medium facial features. The
      participants were fit-tested for three N95 masks of different facepiece design
      and the results compared to facial size distribution specified in the RFTPs of
      bivariate and principal component analysis design developed in this study to
      realize the influence of facial characteristics to respirator fit in relation to
      facepiece design. Nineteen dimensions were measured for 206 participants. In fit
      testing the qualitative fit test (QLFT) procedures prescribed by the U.S.
      Occupational Safety and Health Administration were adopted. As the results show,
      the bizygomatic breadth of the male and female participants were 90.1 and 90.8%
      of their counterparts reported for the U.S. youths (P < 0.001), respectively.
      Compared to the bivariate distribution, the PCA design better accommodated
      variation in facial contours among different respirator user groups or
      populations, with the RFTPs reported in this study and from literature
      consistently covering over 92% of the participants. Overall, the facial fit of
      filtering facepieces increased with increasing facial dimensions. The total
      percentages of the tests wherein the final maneuver being completed was "Moving
      head up-and-down", "Talking" or "Bending over" in bivariate and PCA RFTPs were
      13.3-61.9% and 22.9-52.8%, respectively. The respirators with a three-panel flat
      fold structured in the facepiece provided greater fit, particularly when the
      users moved heads. When the facial size distribution in a bivariate RFTP did not
      sufficiently represent petite facial size, the fit testing was inclined to
      overestimate the general fit, thus for small-to-medium facial dimensions a
      distinct RFTP should be considered.

PMID- 29176834
TI  - Novel scintillating material 2-(4-styrylphenyl)benzoxazole for the fully digital
      and MRI compatible J-PET tomograph based on plastic scintillators.
AB  - A novel plastic scintillator is developed for the application in the digital
      positron emission tomography (PET). The novelty of the concept lies in
      application of the 2-(4-styrylphenyl)benzoxazole as a wavelength shifter. The
      substance has not been used as scintillator dopant before. A dopant shifts the
      scintillation spectrum towards longer wavelengths making it more suitable for
      applications in scintillators of long strips geometry and light detection with
      digital silicon photomultipliers. These features open perspectives for the
      construction of the cost-effective and MRI-compatible PET scanner with the large
      field of view. In this article we present the synthesis method and characterize
      performance of the elaborated scintillator by determining its light emission
      spectrum, light emission efficiency, rising and decay time of the scintillation
      pulses and resulting timing resolution when applied in the positron emission
      tomography. The optimal concentration of the novel wavelength shifter was
      established by maximizing the light output and it was found to be 0.05 0/00 for
      cuboidal scintillator with dimensions of 14 mm x 14 mm x 20 mm.

PMID- 29176836
TI  - Competence in metered dose inhaler technique among community pharmacy
      professionals in Gondar town, Northwest Ethiopia: Knowledge and skill gap
      analysis.
AB  - BACKGROUND: When compared to systemic administration, if used correctly inhalers
      deliver a smaller enough percent of the drug right to the site of action in the
      lungs, with a faster onset of effect and with reduced systemic availability that
      minimizes adverse effects. However, the health professionals' and patients' use
      of metered dose inhaler is poor. OBJECTIVE: This study was aimed to explore
      community pharmacy professionals' (pharmacists' and druggists') competency on
      metered dose inhaler (MDI) technique. METHOD: A cross sectional study was
      employed on pharmacy professionals working in community drug retail outlets in
      Gondar town, northwest Ethiopia from March to May 2017. Evaluation tool was
      originally taken and adapted from the National Asthma Education and Prevention
      Programmes of America (NAEPP) step criteria for the demonstration of a metered
      dose inhaler to score the knowledge/proficiency of using the inhaler. RESULT:
      Among 70 community pharmacy professionals approached, 62 (32 pharmacists and 30
      druggists/Pharmacy technicians) completed the survey with a response rate of
      85.6%. Only three (4.8%) respondents were competent by demonstrating the vital
      steps correctly. Overall, only 13 participants got score seven or above, but most
      of them had missed the essential steps which included steps 1, 2, 5, 6, 7 or 8.
      There was a significant difference (P = 0.015) in competency of demonstrating
      adequate inhalational technique among respondents who took training on basic
      inhalational techniques and who did not. CONCLUSION: This study shown that,
      community pharmacy professionals' competency of MDI technique was very poor. So
      as to better incorporate community pharmacies into future asthma illness
      management and optimize the contribution of pharmacists, interventions would
      emphasis to improve the total competence of community pharmacy professionals
      through establishing and providing regular educational programs.

PMID- 29176835
TI  - Enhanced eicosapentaenoic acid production by a new deep-sea marine bacterium
      Shewanella electrodiphila MAR441T.
AB  - Omega-3 fatty acids are products of secondary metabolism, essential for growth
      and important for human health. Although there are numerous reports of bacterial
      production of omega-3 fatty acids, less information is available on the
      biotechnological production of these compounds from bacteria. The production of
      eicosapentaenoic acid (EPA, 20:5omega3) by a new species of marine bacteria
      Shewanella electrodiphila MAR441T was investigated under different fermentation
      conditions. This strain produced a high percentage (up to 26%) of total fatty
      acids and high yields (mg / g of biomass) of EPA at or below the optimal growth
      temperature. At higher growth temperatures these values decreased greatly. The
      amount of EPA produced was affected by the carbon source, which also influenced
      fatty acid composition. This strain required Na+ for growth and EPA synthesis and
      cells harvested at late exponential or early stationary phase had a higher EPA
      content. Both the highest amounts (20 mg g-1) and highest percent EPA content
      (18%) occurred with growth on L-proline and (NH4)2SO4. The addition of cerulenin
      further enhanced EPA production to 30 mg g-1. Chemical mutagenesis using NTG
      allowed the isolation of mutants with improved levels of EPA content (from 9.7 to
      15.8 mg g-1) when grown at 15 degrees C. Thus, the yields of EPA could be
      substantially enhanced without the need for recombinant DNA technology, often a
      commercial requirement for food supplement manufacture.

PMID- 29176837
TI  - Factors affecting foveal avascular zone in healthy eyes: An examination using
      swept-source optical coherence tomography angiography.
AB  - OBJECTIVE: To examine factors affecting foveal avascular zone (FAZ) area in
      healthy eyes using swept-source optical coherence tomography angiography (OCTA).
      METHODS: This prospective, cross-sectional study included 144 eyes of 144
      individuals (77 women, 67 men) with a best corrected visual acuity of at least
      20/20 and no history of ocular disorders. The area of the superficial FAZ was
      assessed using OCTA. Age, gender, central retinal thickness (CRT), retinal
      vascular density, refractive error, and axial length were examined to determine
      associations with FAZ area. RESULTS: The mean age of the subjects was 42.1 +/-
      20.2 years (range: 10-79 years). The mean FAZ area was 0.32 +/- 0.11 mm2, while
      the mean retinal vascular density was 35.53 +/- 0.92%. Multivariate regression
      analysis was performed using FAZ area as the dependent variable and age, gender,
      CRT, retinal vascular density, refractive error, and axial length as independent
      variables. The results of this analysis demonstrate that CRT and retinal vascular
      density were significantly associated with FAZ area in our sample (P < 0.001, R2
      = 0.425). Age, gender, refractive error, and axial length were not significantly
      correlated with FAZ area, while CRT and retinal vascular density were negatively
      correlated with FAZ area (CRT: P < 0.001, R2 = 0.356; retinal vascular density: P
      < 0.001, R2 = 0.189). CONCLUSIONS: OCTA results suggest that CRT and retinal
      vascular density negatively affect FAZ area in healthy eyes.

PMID- 29176838
TI  - Inhibition of group-I metabotropic glutamate receptors protects against prion
      toxicity.
AB  - Prion infections cause inexorable, progressive neurological dysfunction and
      neurodegeneration. Expression of the cellular prion protein PrPC is required for
      toxicity, suggesting the existence of deleterious PrPC-dependent signaling
      cascades. Because group-I metabotropic glutamate receptors (mGluR1 and mGluR5)
      can form complexes with the cellular prion protein (PrPC), we investigated the
      impact of mGluR1 and mGluR5 inhibition on prion toxicity ex vivo and in vivo. We
      found that pharmacological inhibition of mGluR1 and mGluR5 antagonized dose
      dependently the neurotoxicity triggered by prion infection and by prion-mimetic
      anti-PrPC antibodies in organotypic brain slices. Prion-mimetic antibodies
      increased mGluR5 clustering around dendritic spines, mimicking the toxicity of
      Abeta oligomers. Oral treatment with the mGluR5 inhibitor, MPEP, delayed the
      onset of motor deficits and moderately prolonged survival of prion-infected mice.
      Although group-I mGluR inhibition was not curative, these results suggest that it
      may alleviate the neurological dysfunctions induced by prion diseases.

PMID- 29176839
TI  - Pleistocene climatic oscillations in Neotropical open areas: Refuge isolation in
      the rodent Oxymycterus nasutus endemic to grasslands.
AB  - Pleistocene climatic oscillations favoured the expansion of grassland ecosystems
      and open vegetation landscapes throughout the Neotropics, and influenced the
      evolutionary history of species adapted to such environments. In this study, we
      sampled populations of the rodent Oxymycterus nasutus endemic to open areas in
      the Pampas and Atlantic Forest biomes to assess the tempo and mode of population
      divergence using an integrative approach, including coalescence theory,
      ecological niche models, and morphometry. Our results indicated that these O.
      nasutus populations exhibited high levels of genetic structure. Six major mtDNA
      clades were found, structuring these biomes into distinct groups. Estimates of
      their divergence times was indicated to be 0.571 myr. The high degree of genetic
      structure is reflected in the analyses of geometric morphometric; skull
      differences between lineages in the two ecoregions were detected. During the last
      glacial maximum, there was a strong increase in suitable abiotic conditions for
      O. nasutus. Distinct molecular markers revealed a population expansion over time,
      with a possible demographic retraction during the post-glacial period.
      Considering that all clades coalesce with the last interglacial maximum, our
      results indicated that reduction in suitable conditions during this period may
      have resulted in a possible vicariance associated with refuge isolation.

PMID- 29176840
TI  - Turning poop into profit: Cost-effectiveness and soil transmitted helminth
      infection risk associated with human excreta reuse in Vietnam.
AB  - Human excreta is a low cost source of nutrients vital to plant growth, but also a
      source of pathogens transmissible to people and animals. We investigated the cost
      savings and infection risk of soil transmitted helminths (STHs) in four scenarios
      where farmers used either inorganic fertilizer or fresh/composted human excreta
      supplemented by inorganic fertilizer to meet the nutrient requirements of rice
      paddies in the Red River Delta, Vietnam. Our study included two main components:
      1) a risk estimate of STH infection for farmers who handle fresh excreta,
      determined by systematic review and meta-analysis; and 2) a cost estimate of
      fertilizing rice paddies, determined by nutrient assessment of excreta, a
      retailer survey of inorganic fertilizer costs, and a literature review to
      identify region-specific inputs. Our findings suggest that farmers who reuse
      fresh excreta are 1.24 (95% CI: 1.13-1.37, p-value<0.001) times more likely to be
      infected with any STH than those who do not handle excreta or who compost
      appropriately, and that risk varies by STH type (Ascaris lumbricoides RR = 1.17,
      95% CI = 0.87-1.58, p-value = 0.29; Hookworm RR = 1.02, 95% CI = 0.50-2.06, p
      value = 0.96; Trichuris trichiura RR = 1.38, 95% CI = 0.79-2.42, p-value = 0.26).
      Average cost-savings were highest for farmers using fresh excreta (847,000 VND)
      followed by those who composted for 6 months as recommended by the WHO (312,000
      VND) and those who composted for a shorter time (5 months) with lime
      supplementation (37,000 VND/yr); however, this study did not assess healthcare
      costs of treating acute or chronic STH infections in the target group. Our study
      provides evidence that farmers in the Red River Delta are able to use a renewable
      and locally available resource to their economic advantage, while minimizing the
      risk of STH infection.

PMID- 29176841
TI  - Salient object segmentation based on active contouring.
AB  - Traditional saliency detection algorithms lack object semantic character, and the
      segmentation algorithms cannot highlight the saliency of the segmentation
      regions. In order to compensate for the defects of these two algorithms, the
      salient object segmentation model, which is a novel combination of two
      algorithms, is established in this paper. With the help of a priori knowledge of
      image boundary background traits, the K-means++ algorithm is used to cluster the
      pixels for each region; in line with the sensitivity of the human eye to color
      and with its attention mechanism, the joint probability distribution of the
      regional contrast ratio and spatial saliency is established. The selection of the
      salient area is based on the probabilities, for which the region boundary is
      taken as the initial curve, and the level-set algorithm is used to perform the
      salient object segmentation of the image. The curve convergence condition is
      established according to the confidence level for the segmented region, thus
      avoiding over-convergence of the segmentation curve. With this method, the
      salient region boundary is adjacent to the object contour, so the curve evolution
      time is shorter, and compared with the traditional Li algorithm, the proposed
      algorithm has higher segmentation evaluation scores, with the additional benefit
      of emphasizing the importance of the object.

PMID- 29176842
TI  - Allergenic food introduction and risk of childhood atopic diseases.
AB  - BACKGROUND: The role of timing and diversity of allergenic food introduction in
      the development of childhood allergic sensitization and atopic diseases is
      controversial. OBJECTIVE: To examine whether timing and diversity of allergenic
      food introduction are associated with allergic sensitization, allergy and eczema
      in children until age 10 years. MATERIALS AND METHODS: This study among 5,202
      children was performed in a population-based prospective cohort. Timing (age <=6
      months vs. >6 months) and diversity (0, 1, 2 and >=3 foods) of allergenic food
      (cow's milk, hen's egg, peanut, tree nuts, soy and gluten) introduction were
      assessed by questionnaires at ages 6 and 12 months. At age 10 years, inhalant and
      food allergic sensitization were measured by skin prick tests, and physician
      diagnosed inhalant and food allergy by questionnaire. Data on parental-reported
      physician-diagnosed eczema were obtained from birth until age 10 years. RESULTS:
      Children introduced to gluten at age <=6 months had a decreased risk of eczema
      (aOR (95% CI): 0.84 (0.72, 0.99)), compared with children introduced to gluten at
      age >6 months. However, timing of allergenic food introduction was not associated
      with allergic sensitization or physician-diagnosed allergy. Children introduced
      to >=3 allergenic foods at age <=6 months had a decreased risk of physician
      diagnosed inhalant allergy (0.64 (0.42, 0.98)), compared with children not
      introduced to any allergenic food at age <=6 months. However, diversity of
      allergenic food introduction was not associated with allergic sensitization,
      physician-diagnosed food allergy or eczema. CONCLUSION: Neither timing nor
      diversity of allergenic food introduction was consistently associated with
      childhood allergic sensitization, allergy or eczema.

PMID- 29176843
TI  - HIV-1 and cocaine disrupt dopamine reuptake and medium spiny neurons in female
      rat striatum.
AB  - HIV-1 and addictive drugs, such as cocaine (COC), may act in combination to
      produce serious neurological complications. In the present experiments, striatal
      brain slices from HIV-1 transgenic (Tg) and F344 control female rats were
      studied. First, we examined dopamine (DA) reuptake in control, HIV-1, COC-treated
      (5uM) and HIV-1+COC-treated, striatal slices using fast scan cyclic voltammetry.
      COC-treated striatal slices from F344 control animals significantly increased DA
      reuptake time (T80), relative to untreated control slices. In contrast, in HIV-1
      Tg striatal slices, DA reuptake time was extended by HIV-1, which was not further
      altered by COC treatment. Second, analysis of medium spiny neuronal populations
      from striatal brain slices found that controls treated with cocaine displayed
      increases in spine length, whereas cocaine treated HIV-1 slices displayed
      decreased spine length. Taken together, the current study provides evidence for
      dysfunction of the dopamine transporter (DAT) in mediating DA reuptake in HIV-1
      Tg rats and limited responses to acute COC exposure. Collectively, dysfunction of
      the DAT reuptake and altered dendritic spine morphology of the MSNs, suggest a
      functional disruption of the dopamine system within the HIV-1 Tg rat.

PMID- 29176844
TI  - Prospective comparison among transient elastography, supersonic shear imaging,
      and ARFI imaging for predicting fibrosis in nonalcoholic fatty liver disease.
AB  - The diagnostic performance of supersonic shear imaging (SSI) in comparison with
      those of transient elastography (TE) and acoustic radiation force impulse imaging
      (ARFI) for staging fibrosis in nonalcoholic fatty liver disease (NAFLD) patients
      has not been fully assessed, especially in Asian populations with relatively lean
      NAFLD compared to white populations. Thus, we focused on comparing the diagnostic
      performances of TE, ARFI, and SSI for staging fibrosis in a head-to-head manner,
      and identifying the clinical, anthropometric, biochemical, and histological
      features which might affect liver stiffness measurement (LSM) in our prospective
      biopsy-proven NAFLD cohort. In this study, ninety-four patients with biopsy
      proven NAFLD were included prospectively. Liver stiffness was measured using TE,
      SSI, and ARFI within 1 month of liver biopsy. The diagnostic performance for
      staging fibrosis was assessed using receiver operating characteristic (ROC)
      analysis. Anthropometric data were evaluated as covariates influencing LSM by
      regression analyses. Liver stiffness correlated with fibrosis stage (p < 0.05);
      the area under the ROC curve of TE (kPa), SSI (kPa), and ARFI (m/s) were as
      follows: 0.757, 0.759, and 0.657 for significant fibrosis and 0.870, 0.809, and
      0.873 for advanced fibrosis. Anthropometric traits were significant confounders
      affecting SSI, while serum liver injury markers significantly confounded TE and
      ARFI. In conclusion, the LSM methods had similar diagnostic performance for
      staging fibrosis in patients with NAFLD. Pre-LSM anthropometric evaluation may
      help predict the reliability of SSI.

PMID- 29176845
TI  - Minimal 2'-O-methyl phosphorothioate linkage modification pattern of synthetic
      guide RNAs for increased stability and efficient CRISPR-Cas9 gene editing
      avoiding cellular toxicity.
AB  - Since its initial application in mammalian cells, CRISPR-Cas9 has rapidly become
      a preferred method for genome engineering experiments. The Cas9 nuclease is
      targeted to genomic DNA using guide RNAs (gRNA), either as the native dual RNA
      system consisting of a DNA-targeting CRISPR RNA (crRNA) and a trans-activating
      crRNA (tracrRNA), or as a chimeric single guide RNA (sgRNA). Entirely DNA-free
      CRISPR-Cas9 systems using either Cas9 protein or Cas9 mRNA and chemically
      synthesized gRNAs allow for transient expression of CRISPR-Cas9 components,
      thereby reducing the potential for off-targeting, which is a significant
      advantage in therapeutic applications. In addition, the use of synthetic gRNA
      allows for the incorporation of chemical modifications for enhanced properties
      including improved stability. Previous studies have demonstrated the utility of
      chemically modified gRNAs, but have focused on one pattern with multiple
      modifications in co-electroporation with Cas9 mRNA or multiple modifications and
      patterns with Cas9 plasmid lipid co-transfections. Here we present gene editing
      results using a series of chemically modified synthetic sgRNA molecules and
      chemically modified crRNA:tracrRNA molecules in both electroporation and lipid
      transfection assessing indel formation and/or phenotypic gene knockout. We show
      that while modifications are required for co-electroporation with Cas9 mRNA, some
      modification patterns of the gRNA are toxic to cells compared to the unmodified
      gRNA and most modification patterns do not significantly improve gene editing
      efficiency. We also present modification patterns of the gRNA that can modestly
      improve Cas9 gene editing efficiency when co-transfected with Cas9 mRNA or Cas9
      protein (> 1.5-fold difference). These results indicate that for certain
      applications, including those relevant to primary cells, the incorporation of
      some, but not all chemical modification patterns on synthetic crRNA:tracrRNA or
      sgRNA can be beneficial to CRISPR-Cas9 gene editing.

PMID- 29176846
TI  - Effect of drying procedures on the physicochemical properties and antioxidant
      activities of polysaccharides from Crassostrea gigas.
AB  - Crassostrea gigas polysaccharides (CGP) were obtained by different drying
      methods: freeze-drying (FD), spray-drying (SD) or rotary evaporation-drying
      (RED). The physicochemical properties of CGP were evaluated on the basis of
      polysaccharide content, protein content, color characteristics, FT-IR
      spectroscopy, differential scanning calorimetry (DSC), and scanning electron
      microscopy (SEM). Antioxidant activities were researched three different free
      radicals, including DPPH free radicals, ABTS free radicals and reducing power.
      The results demonstrated that FDCGP, SDCGP and REDCGP have different
      physicochemical properties and antioxidant activities. Contrasted with FDCGP and
      REDCGP, SDCGP exhibited stronger antioxidant abilities. Therefore, considering
      the polysaccharides appearances and antioxidant activities, the spray drying
      method is a decent selection for the preparation of such polysaccharides, and it
      should be selected for application in the food industry.

PMID- 29176847
TI  - Strawberry: Fast and accurate genome-guided transcript reconstruction and
      quantification from RNA-Seq.
AB  - : We propose a novel method and software tool, Strawberry, for transcript
      reconstruction and quantification from RNA-Seq data under the guidance of genome
      alignment and independent of gene annotation. Strawberry consists of two modules:
      assembly and quantification. The novelty of Strawberry is that the two modules
      use different optimization frameworks but utilize the same data graph structure,
      which allows a highly efficient, expandable and accurate algorithm for dealing
      large data. The assembly module parses aligned reads into splicing graphs, and
      uses network flow algorithms to select the most likely transcripts. The
      quantification module uses a latent class model to assign read counts from the
      nodes of splicing graphs to transcripts. Strawberry simultaneously estimates the
      transcript abundances and corrects for sequencing bias through an EM algorithm.
      Based on simulations, Strawberry outperforms Cufflinks and StringTie in terms of
      both assembly and quantification accuracies. Under the evaluation of a real data
      set, the estimated transcript expression by Strawberry has the highest
      correlation with Nanostring probe counts, an independent experiment measure for
      transcript expression. AVAILABILITY: Strawberry is written in C++14, and is
      available as open source software at https://github.com/ruolin/strawberry under
      the MIT license.

PMID- 29176848
TI  - Dynamics of epizootic hemorrhagic disease virus infection within the vector,
      Culicoides sonorensis (Diptera: Ceratopogonidae).
AB  - Culicoides sonorensis biting midges are confirmed vectors of epizootic
      hemorrhagic disease virus (EHDV), which causes mortality in white-tailed deer and
      ruminant populations. Currently, of the seven EHDV serotypes, only 1, 2, and 6
      are detected in the USA, and very few studies have focused on the infection time
      course of these serotypes within the midge. The objective of this current
      research was to characterize EHDV-2 infection within the midge by measuring
      infection prevalence, virus dissemination, and viral load over the course of
      infection. Midges were fed a blood meal containing 106.9 PFU/ml EHDV-2, collected
      every 12 h from 0-2 days post feeding (dpf) and daily from 3-10 dpf, and cohorts
      of 20 C. sonorensis were processed using techniques that assessed EHDV infection
      and dissemination. Cytopathic effect assays and quantitative (q)PCR were used to
      determine infection prevalence, revealing a 50% infection rate by 10 dpf using
      both methods. Using immunohistochemistry, EHDV-2 infection was detectable at 5
      dpf, and shown to disseminate from the midgut to other tissues, including fat
      body, eyes, and salivary glands by 5 dpf. Stain intensity increased from 5-8 dpf,
      indicating replication of EHDV-2 in secondary infection sites after
      dissemination. This finding is also supported by trends in viral load over time
      as determined by plaque assays and qPCR. An increase in titer between 4-5 dpf
      correlated with viral replication in the midgut as seen with staining at day 5,
      while the subsequent gradual increase in viral load from 8-10 dpf suggested viral
      replication in midges with disseminated infection. Overall, the data presented
      herein suggest that EHDV-2 disseminates via the hemolymph to secondary infection
      sites throughout the midge and demonstrate a high potential for transmission at
      five days at 25 degrees C after an infective blood-meal.

PMID- 29176849
TI  - Association between non-barrier modern contraceptive use and condomless sex among
      HIV-positive female sex workers in Mombasa, Kenya: A prospective cohort analysis.
AB  - BACKGROUND: As access to antiretroviral therapy in sub-Saharan Africa continues
      to expand, more women with HIV can expect to survive through their reproductive
      years. Modern contraceptives can help women choose the timing and spacing of
      childbearing. However, concerns remain that women with HIV who use non-barrier
      forms of modern contraception may engage in more condomless sex because of their
      decreased risk of unintended pregnancy. We examined whether non-barrier modern
      contraceptive use by HIV-positive female sex workers was associated with
      increased frequency of recent condomless sex, measured by detection of prostate
      specific antigen (PSA) in vaginal secretions. METHODS: Women who were HIV
      positive and reported transactional sex were included in this analysis. Pregnant
      and post-menopausal follow-up time was excluded, as were visits at which women
      reported trying to get pregnant. At enrollment and quarterly follow-up visits, a
      pelvic speculum examination with collection of vaginal secretions was conducted
      for detection of PSA. In addition, women completed a structured face-to-face
      interview about their current contraceptive methods and sexual risk behavior at
      enrollment and monthly follow-up visits. Log-binomial generalized estimating
      equations regression was used to test for associations between non-barrier modern
      contraceptive use and detection of PSA in vaginal secretions and self-reported
      condomless sex. Data from October 2012 through September 2014 were included in
      this analysis. RESULTS: Overall, 314 women contributed 1,583 quarterly
      examination visits. There was minimal difference in PSA detection at
      contraceptive-exposed versus contraceptive-unexposed visits (adjusted relative
      risk [aRR] 1.28, 95% confidence interval [95% CI] 0.93-1.76). There was a higher
      rate of self-reported condomless sex at visits where women reported using modern
      contraceptives, but this difference was not statistically significant after
      adjustment for potential confounding factors (aRR 1.59, 95% CI 0.98-2.58).
      CONCLUSION: Non-barrier methods of modern contraception were not associated with
      increased risk of objective evidence of condomless sex.

PMID- 29176850
TI  - A 23-year retrospective investigation of Salmonella Typhi and Salmonella
      Paratyphi isolated in a tertiary Kathmandu hospital.
AB  - BACKGROUND: Salmonella serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi
      A), the causative agents of enteric fever, have been routinely isolated organisms
      from the blood of febrile patients in the Kathmandu Valley since the early 1990s.
      Susceptibility against commonly used antimicrobials for treating enteric fever
      has gradually changed throughout South Asia since this time, posing serious
      treatment challenges. Here, we aimed to longitudinally describe trends in the
      isolation of Salmonella enterica and assess changes in their antimicrobial
      susceptibility in Kathmandu over a 23-year period. METHODS: We conducted a
      retrospective analysis of standardised microbiological data from April 1992 to
      December 2014 at a single healthcare facility in Kathmandu, examining time trends
      of Salmonella-associated bacteraemia and the corresponding antimicrobial
      susceptibility profiles of the isolated organisms. RESULTS: Over 23 years there
      were 30,353 positive blood cultures. Salmonella enterica accounted for 65.4%
      (19,857/30,353) of all the bacteria positive blood cultures. S. Typhi and S.
      Paratyphi A were the dominant serovars, constituting 68.5% (13,592/19,857) and
      30.5% (6,057/19,857) of all isolated Salmonellae. We observed (i) a peak in the
      number of Salmonella-positive cultures in 2002, a year of heavy rainfall and
      flooding in the Kathmandu Valley, followed by a decline toward pre-flood baseline
      by 2014, (ii) an increase in the proportion of S. Paratyphi in all Salmonella
      positive cultures between 1992 and 2014, (iii) a decrease in the prevalence of
      MDR for both S. Typhi and S. Paratyphi, and (iv) a recent increase in
      fluoroquinolone non-susceptibility in both S. Typhi and S. Paratyphi isolates.
      CONCLUSIONS: Our work describes significant changes in the epidemiology of
      Salmonella enterica in the Kathmandu Valley during the last quarter of a century.
      We highlight the need to examine current treatment protocols for enteric fever
      and suggest a change from fluoroquinolone monotherapy to combination therapies of
      macrolides or cephalosporins along with older first-line antimicrobials that have
      regained their efficacy.

PMID- 29176851
TI  - Economics of One Health: Costs and benefits of integrated West Nile virus
      surveillance in Emilia-Romagna.
AB  - Since 2013 in Emilia-Romagna, Italy, surveillance information generated in the
      public health and in the animal health sectors has been shared and used to guide
      public health interventions to mitigate the risk of West Nile virus (WNV)
      transmission via blood transfusion. The objective of the current study was to
      identify and estimate the costs and benefits associated with this One Health
      surveillance approach, and to compare it to an approach that does not integrate
      animal health information in blood donations safety policy (uni-sectoral
      scenario). Costs of human, animal, and entomological surveillance, sharing of
      information, and triggered interventions were estimated. Benefits were quantified
      as the averted costs of potential human cases of WNV neuroinvasive disease
      associated to infected blood transfusion. In the 2009-2015 period, the One Health
      approach was estimated to represent a cost saving of ?160,921 compared to the uni
      sectoral scenario. Blood donation screening was the main cost for both scenarios.
      The One Health approach further allowed savings of ?1.21 million in terms of
      avoided tests on blood units. Benefits of the One Health approach due to short
      term costs of hospitalization and compensation for transfusion-associated disease
      potentially avoided, were estimated to range from ?0 to ?2.98 million according
      to the probability of developing WNV neuroinvasive disease after receiving an
      infected blood transfusion.

PMID- 29176852
TI  - How does trust affect acceptance of a nuclear power plant (NPP): A survey among
      people living with Qinshan NPP in China.
AB  - It is difficult to know whether different dimensions of trust have different
      effects on local residents' acceptance of nuclear power plants (NPPs). In
      previous research such trust has been considered as a single dimensional concept.
      This paper divides trust into goodwill trust and competence trust, and we explore
      the ways in which trust affects acceptance of NPPs through structural equation
      modeling. A survey of 491 people was conducted in Haiyan County, China, where the
      Qinshan nuclear power plant is located. We find that goodwill trust is
      significantly correlated with competence trust, and each can indirectly promote
      residents' acceptance of NPPs but by different paths. Goodwill trust improves
      acceptance of NPPs by decreasing risk perception, while competence trust improves
      acceptance of NPPs by increasing benefit perception. However, the associations
      between goodwill trust and benefit perception, competence trust and risk
      perception, are not significant.

PMID- 29176853
TI  - Age-related changes in oscillatory power affect motor action.
AB  - With increasing age cognitive performance slows down. This includes cognitive
      processes essential for motor performance. Additionally, performance of motor
      tasks becomes less accurate. The objective of the present study was to identify
      general neural correlates underlying age-related behavioral slowing and the
      reduction in motor task accuracy. To this end, we continuously recorded EEG
      activity from 18 younger and 24 older right-handed healthy participants while
      they were performing a simple finger tapping task. We analyzed the EEG records
      with respect to local changes in amplitude (power spectrum) as well as phase
      locking between the two age groups. We found differences between younger and
      older subjects in the amplitude of post-movement synchronization in the beta band
      of the sensory-motor and medial prefrontal cortex (mPFC). This post-movement beta
      amplitude was significantly reduced in older subjects. Moreover, it positively
      correlated with the accuracy with which subjects performed the motor task at the
      electrode FCz, which detects activity of the mPFC and the supplementary motor
      area. In contrast, we found no correlation between the accurate timing of local
      neural activity, i.e. phase locking in the delta-theta frequency band, with the
      reaction and movement time or the accuracy with which the motor task was
      performed. Our results show that only post-movement beta amplitude and not delta
      theta phase locking is involved in the control of movement accuracy. The
      decreased post-movement beta amplitude in the mPFC of older subjects hints at an
      impaired deactivation of this area, which may affect the cognitive control of
      stimulus-induced motor tasks and thereby motor output.

PMID- 29176855
TI  - Comparison of the external physical damages between laser-assisted and mechanical
      immobilized human sperm using scanning electronic microscopy.
AB  - We aim to visualize the external physical damages and distinct external
      phenotypic effects between mechanical and laser-assisted immobilized human
      spermatozoa using scanning electronic microscopy (SEM). Human spermatozoa were
      immobilized mechanically or with laser assistance for SEM examination and the
      membrane integrities were checked on both types of immobilized spermatozoa. We
      found evidence of external damages at SEM level on mechanically kinked sperm, but
      not on laser-assisted immobilized sperm. Although no external damage was found on
      laser-assist immobilized sperm, there were two distinct types of morphological
      changes when spermatozoa were stricken by infra-red laser. Coiled tails were
      immediately formed when Laser pulse was applied to the sperm end piece area,
      whereas laser applied to the sperm principal piece area resulted in a sharp bend
      of sperm tails. Sperm immobilized by laser did not exhibit any morphological
      change if the laser did not hit within the on-screen central target zone or if
      the laser hit the sperm mid piece or head. Our modified membrane integrity assay
      revealed that the external membrane of more than half of the laser-assisted
      immobilized sperm remained intact. In conclusion, mechanical immobilization
      produced membrane damages whilst laser-assisted immobilization did not result in
      any external membrane damages besides morphological changes at SEM level.

PMID- 29176854
TI  - Socioeconomic differential in self-assessment of health and happiness in 5
      African countries: Finding from World Value Survey.
AB  - OBJECTIVE: Factors that contribute to wealth related inequalities in self-rated
      health (SRH) and happiness remains unclear most especially in sub-Saharan
      countries (SSA). This study aims to explore and compare socioeconomic
      differentials in SRH and happiness in five SSA countries. METHODS: Using the
      2010/2014 World Values Survey (WVS), we obtained a sample of 9,869 participants
      of age 16 and above from five SSA countries (Nigeria, Ghana, South Africa, Rwanda
      and Zimbabwe). Socioeconomic inequalities were quantified using the concentration
      index. The contribution of each predictor to concentration index's magnitude was
      obtained by means of regression based decomposition analysis. RESULTS: Poor SRH
      ranges from approximately 9% in Nigeria to 20% in Zimbabwe, whereas unhappiness
      was lower in Rwanda (9.5%) and higher in South Africa (23.3%). Concentration
      index was negative for both outcomes in all countries, which implies that poor
      SRH and unhappiness are excessively concentrated among the poorest socioeconomic
      strata. Although magnitudes differ across countries, however, the major
      contributor to wealth-related inequality in poor SRH is satisfaction with
      financial situation whereas for unhappiness the major contributors are level of
      income and satisfaction with financial situation. CONCLUSIONS: This study
      underscores an association between wealth related inequalities and poor SRH and
      unhappiness in the context of SSA. Improving equity in health, as suggested by
      the commission of social determinants of health may be useful in fighting against
      the unfair distribution of resources. Thus, knowledge about the self-rating of
      health and happiness can serve as proxy estimates for understanding the
      distribution of health care access and economic resources needed for well-being
      in resident countries.

PMID- 29176856
TI  - Prenatal androgen-receptor activity has organizational morphological effects in
      mice.
AB  - Prenatal sex hormones exert organizational effects. It has been suggested that
      prenatal sex hormones affect adult morphological parameters, such as the finger
      length. Especially the second-to-fourth finger length (2D:4D) ratio has been
      implicated to be modified when exposed to higher androgen levels in utero. Here
      we show in a mouse model that experimental manipulation of the prenatal androgen
      level, by blocking the androgen receptor with flutamide or activating the
      androgen receptor with dihydrotestosterone (DHT), leads to changes in the length
      of the fingers of all paws in males and females. In addition to that, also total
      paw length and the 2D:4D ratio was affected. In males treated with DHT, the 2D:4D
      ratio was increased, while flutamide-treatment in females led to a reduced 2D:4D
      ratio. We also measured other parameters, such as head size, body length and tail
      length and demonstrate that body morphology is affected by prenatal androgen
      exposure with more prominent effects in females. Another factor that is thought
      to be influenced by early androgens is handedness. We tested mice for handedness,
      but did not find a significant effect of the prenatal treatment. These findings
      demonstrate that prenatal androgen activity is involved in the development of
      body morphology and might be a useful marker for prenatal androgen exposure.

PMID- 29176857
TI  - Prevalence of fimA genotypes of Porphyromonas gingivalis in adolescent
      orthodontic patients.
AB  - BACKGROUND: The placement of fixed orthodontic appliances may alter the
      composition of oral microbiota and has the potential risk of periodontal
      complication. Porphyromonas gingivalis fimbriae play a critical role in
      colonization of P. gingivalis in subgingival regions. In this study, we
      investigated the association between the prevalence of P. gingivalis-specific
      fimA genotypes and periodontal health status in adolescent orthodontic patients,
      to identify the pathogencity of P. gingivalis during orthodontic therapy.
      METHODS: Sixty-one adolescent orthodontic patients were enrolled in the case
      group, while the control group consisted of 56 periodontally healthy adolescents.
      At baseline (T0), clinical parameter (gingival index) was tested, and subgingival
      plaque samples were obtained from the lower incisors. The incidences of P.
      gingivalis and fimA genotypes were detected by polymerase chain reaction. All
      parameters were reassessed after 1 month (T1), 2 months (T2), 3 months (T3), and
      6 months (T4) in the case group and then compared with those of the controls.
      RESULTS: Both microbiological and clinical parameters from orthodontic patients
      started to increase after placement of fixed appliances. Maximum values were
      reached at 3 months after placement and followed by their decreases at six
      months. However, the microbiological and clinical parameters in the case group
      were significantly higher than those of the control group. The GI of fimA II, IV
      positive samples was significantly higher than that of negative samples.
      CONCLUSION: P. gingivalis carrying fimA II or IV was closely related to
      orthodontic gingivitis. In addition, proper oral hygiene control could lead to
      little increase in dental plaque accumulation, and exert a beneficial effect to
      periodontal tissues.

PMID- 29176858
TI  - Sepsis-induced selective loss of NMDA receptors modulates hippocampal
      neuropathology in surviving septic mice.
AB  - BACKGROUND: Sepsis-induced neuroinflammation plays an important role in sepsis
      related brain dysfunction. However, the molecules that are targeted during
      neuroinflammation resulting from sepsis-induced brain dysfunction remain unclear.
      Herein, we tried to investigate the expression and roles of NMDA receptor
      subunits during sepsis-related brain dysfunction. METHODS: Sepsis was induced by
      cecal ligation and perforation (CLP) or by a single intraperitoneal injection of
      lipopolysaccharide (LPS, 8 mg/kg) in C57BL/6J mice. The NMDA receptor co-agonist
      D-serine was injected intraperitoneally for 3 days (500 mg/kg/day) to compensate
      for the loss of NMDA receptors. The behaviors of mice were tested in the Barnes
      maze and in the open field test. The mice were euthanized at the indicated time
      points. The brains were collected to detect the following: the levels of
      synaptophysin and NMDA receptor subunits GluN2A, GluN2B and GluN1 (by Western
      blot and RT-PCR); the number of CA1 neurons (by Nissl staining); neuronal
      activity (by p-CREB staining); neuroinflammation (by staining of Iba-1 and
      inflammatory factors IL-1beta, TNF-alpha, NLRP3); and the levels of oxidative
      stress [by dihydroethidium (DHE)]. RESULTS: Sepsis selectively decreased the
      protein and mRNA levels of GluN2A, GluN2B and GluN1 but not the levels of
      synaptophysin or the neuronal number in the hippocampus of mice in either of the
      classic CLP-induced or LPS-induced sepsis models during the first 7 days after
      sepsis. Intraperitoneal injection of D-serine obviously limited the
      lipopolysaccharide-induced changes, including the impairment of learning and
      memory, the loss of NMDA receptor subunits, robust neuroinflammation, the levels
      of ROS stress and the decrease of p-CREB in the hippocampus of mice. CONCLUSION:
      These data suggest that the sepsis-induced selective loss of NMDA receptors
      modulates hippocampal neuropathology in the mice that survived sepsis, and the
      data show that NMDA receptors are potential targets for the improvement of brain
      dysfunction in sepsis survivors.

PMID- 29176859
TI  - High efficiency cabin air filter in vehicles reduces drivers' roadway particulate
      matter exposures and associated lipid peroxidation.
AB  - Commuters who spend long hours on roads are exposed to high levels of traffic
      related air pollutants (TRAPs). Despite some well-known multiple adverse effects
      of TRAPs on human health, limited studies have focused on mitigation strategies
      to reduce these effects. In this study, we measured fine particulate matter
      (PM2.5) and ultrafine particle (UFP) concentrations inside and outside 17 taxis
      simultaneously while they were driven on roadways. The drivers' urinary
      monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and malondialdehyde
      (MDA) concentrations just before and right after the driving tests were also
      determined. Data were collected under three driving conditions (i.e. no
      mitigation (NM), window closed (WC), and window closed plus using high efficiency
      cabin air filters (WC+HECA)) for each taxi and driver. The results show that,
      compared to NM, the WC+HECA reduced in-cabin PM2.5 and UFP concentrations, by 37%
      and 47% respectively (p < 0.05), whereas the reductions on PAH exposures were
      insignificant. Although nonsignificant, a reduction of 17% was also observed in
      the drivers' urinary MDA under WC+HECA. The MDA concentrations were found to be
      significantly associated with the in-cabin PM2.5 and UFP concentrations,
      suggesting the reduction of the drivers' lipid peroxidation can be at least
      partially attributed to the PM2.5 and UFP reduction by WC+HECA. Overall, these
      results suggest HECA filters have potential to reduce particle levels inside
      taxis and protect drivers' health.

PMID- 29176860
TI  - Identifying species from the air: UAVs and the very high resolution challenge for
      plant conservation.
AB  - The Pacific Equatorial dry forest of Northern Peru is recognised for its unique
      endemic biodiversity. Although highly threatened the forest provides livelihoods
      and ecosystem services to local communities. As agro-industrial expansion and
      climatic variation transform the region, close ecosystem monitoring is essential
      for viable adaptation strategies. UAVs offer an affordable alternative to
      satellites in obtaining both colour and near infrared imagery to meet the
      specific requirements of spatial and temporal resolution of a monitoring system.
      Combining this with their capacity to produce three dimensional models of the
      environment provides an invaluable tool for species level monitoring. Here we
      demonstrate that object-based image analysis of very high resolution UAV images
      can identify and quantify keystone tree species and their health across wide
      heterogeneous landscapes. The analysis exposes the state of the vegetation and
      serves as a baseline for monitoring and adaptive implementation of community
      based conservation and restoration in the area.

PMID- 29176861
TI  - Variables that influence BRAF mutation probability: A next-generation sequencing,
      non-interventional investigation of BRAFV600 mutation status in melanoma.
AB  - BACKGROUND: The incidence of melanoma, particularly in older patients, has
      steadily increased over the past few decades. Activating mutations of BRAF, the
      majority occurring in BRAFV600, are frequently detected in melanoma; however, the
      prognostic significance remains unclear. This study aimed to define the
      probability and distribution of BRAFV600 mutations, and the clinico-pathological
      factors that may affect BRAF mutation status, in patients with advanced melanoma
      using next-generation sequencing. MATERIALS AND METHODS: This was a non
      interventional, retrospective study of BRAF mutation testing at two German
      centers, in Heidelberg and Tubingen. Archival tumor samples from patients with
      histologically confirmed melanoma (stage IIIB, IIIC, IV) were analyzed using PCR
      amplification and deep sequencing. Clinical, histological, and mutation data were
      collected. The statistical influence of patient- and tumor-related
      characteristics on BRAFV600 mutation status was assessed using multiple logistic
      regression (MLR) and a prediction profiler. RESULTS: BRAFV600 mutation status was
      assessed in 453 samples. Mutations were detected in 57.6% of patients (n = 261),
      with 48.1% (n = 102) at the Heidelberg site and 66.0% (n = 159) at the Tubingen
      site. The decreasing influence of increasing age on mutation probability was
      quantified. A main effects MLR model identified age (p = 0.0001), center (p =
      0.0004), and melanoma subtype (p = 0.014) as significantly influencing BRAFV600
      mutation probability; ultraviolet (UV) exposure showed a statistical trend (p =
      0.1419). An interaction model of age versus other variables showed that center
      (p<0.0001) and melanoma subtype (p = 0.0038) significantly influenced BRAF
      mutation probability; age had a statistically significant effect only as part of
      an interaction with both UV exposure (p = 0.0110) and melanoma subtype (p =
      0.0134). CONCLUSIONS: This exploratory study highlights that testing center,
      melanoma subtype, and age in combination with UV exposure and melanoma subtype
      significantly influence BRAFV600 mutation probability in patients with melanoma.
      Further validation of this model, in terms of reproducibility and broader
      relevance, is required.

PMID- 29176862
TI  - Plant-type phytoene desaturase: Functional evaluation of structural implications.
AB  - Phytoene desaturase (PDS) is an essential plant carotenoid biosynthetic enzyme
      and a prominent target of certain inhibitors, such as norflurazon, acting as
      bleaching herbicides. PDS catalyzes the introduction of two double bonds into 15
      cis-phytoene, yielding 9,15,9'-tri-cis-zeta-carotene via the intermediate 9,15-di
      cis-phytofluene. We present the necessary data to scrutinize functional
      implications inferred from the recently resolved crystal structure of Oryza
      sativa PDS in a complex with norflurazon. Using dynamic mathematical modeling of
      reaction time courses, we support the relevance of homotetrameric assembly of the
      enzyme observed in crystallo by providing evidence for substrate channeling of
      the intermediate phytofluene between individual subunits at membrane surfaces.
      Kinetic investigations are compatible with an ordered ping-pong bi-bi kinetic
      mechanism in which the carotene and the quinone electron acceptor successively
      occupy the same catalytic site. The mutagenesis of a conserved arginine that
      forms a hydrogen bond with norflurazon, the latter competing with plastoquinone,
      corroborates the possibility of engineering herbicide resistance, however, at the
      expense of diminished catalytic activity. This mutagenesis also supports a
      "flavin only" mechanism of carotene desaturation not requiring charged residues
      in the active site. Evidence for the role of the central 15-cis double bond of
      phytoene in determining regio-specificity of carotene desaturation is presented.

PMID- 29176863
TI  - Life events and hopelessness depression: The influence of affective experience.
AB  - This study explored the association of the affective experience (AE) of life
      events on hopelessness depression (HD). Undergraduates (N = 301) participating in
      a 12-week prospective study completed measures of HD, cognitive style, and
      psychological stress. The results indicate AE is an underlying mechanism
      influencing the longitudinal link between life events and HD. Negative life
      events with clear negative AE directly promoted the development of HD. Positive
      life events with clear positive AE directly impeded the development of HD.
      Neutral life events with mixed AE directly and interacting with negative
      cognitive style promoted the development of HD. The results should increase
      understanding of the hopelessness theory of depression, and suggest that neutral
      life events should be important elements in depression therapy.

PMID- 29176864
TI  - Health assessment of French university students and risk factors associated with
      mental health disorders.
AB  - OBJECTIVE: The first year of university is a particularly stressful period and
      can impact academic performance and students' health. The aim of this study was
      to evaluate the health and lifestyle of undergraduates and assess risk factors
      associated with psychiatric symptoms. MATERIALS AND METHODS: Between September
      2012 and June 2013, we included all undergraduate students who underwent
      compulsory a medical visit at the university medical service in Nice (France)
      during which they were screened for potential diseases during a diagnostic
      interview. Data were collected prospectively in the CALCIUM database
      (Consultations Assistes par Logiciel pour les Centres Inter-Universitaire de
      Medecine) and included information about the students' lifestyle (living
      conditions, dietary behavior, physical activity, use of recreational drugs). The
      prevalence of psychiatric symptoms related to depression, anxiety and panic
      attacks was assessed and risk factors for these symptoms were analyzed using
      logistic regression. RESULTS: A total of 4,184 undergraduates were included.
      Prevalence for depression, anxiety and panic attacks were 12.6%, 7.6% and 1.0%,
      respectively. During the 30 days preceding the evaluation, 0.6% of the students
      regularly drank alcohol, 6.3% were frequent-to-heavy tobacco smokers, and 10.0%
      smoked marijuana. Dealing with financial difficulties and having learning
      disabilities were associated with psychiatric symptoms. Students who were
      dissatisfied with their living conditions and those with poor dietary behavior
      were at risk of depression. Being a woman and living alone were associated with
      anxiety. Students who screened positively for any psychiatric disorder assessed
      were at a higher risk of having another psychiatric disorder concomitantly.
      CONCLUSION: The prevalence of psychiatric disorders in undergraduate students is
      low but the rate of students at risk of developing chronic disease is far from
      being negligible. Understanding predictors for these symptoms may improve
      students' health by implementing targeted prevention campaigns. Further research
      in other French universities is necessary to confirm our results.

PMID- 29176865
TI  - Pre-clinical antigenicity studies of an innovative multivalent vaccine for human
      visceral leishmaniasis.
AB  - The notion that previous infection by Leishmania spp. in endemic areas leads to
      robust anti-Leishmania immunity, supports vaccination as a potentially effective
      approach to prevent disease development. Nevertheless, to date there is no
      vaccine available for human leishmaniasis. We optimized and assessed in vivo the
      safety and immunogenicity of an innovative vaccine candidate against human
      visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with
      three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as
      the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived
      (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse
      reactions were observed during the experimental time-frame, which together with
      the normal hematological parameters detected seems to point to the safety of the
      formulation. Furthermore, measurements of antigen-specific cellular and humoral
      responses, generally higher in immunized versus control groups, confirmed the
      immunogenicity of the vaccine formulation. Interestingly, the immune responses
      against the VD protein were reproducibly more robust than those elicited against
      leishmanial antigens, and were apparently not caused by immunodominance of the VD
      antigen. Remarkably, priming with the VD protein alone and boosting with the
      complete vaccine candidate contributed towards an increase of the immune
      responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and
      CD8+ T cell proliferation against both the PD antigens and total Leishmania
      antigen (TLA). Overall, our immunogenicity data indicate that this innovative
      vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy
      deserves to be tested in the context of the "natural infection".

PMID- 29176866
TI  - Quercetin metabolism by fecal microbiota from healthy elderly human subjects.
AB  - Quercetin is a polyphenol found in food that has numerous health benefits. This
      study investigated the relationship between quercetin metabolism, gut microbiota
      composition, and dietary intake in elderly Japanese subjects. A food frequency
      questionnaire was used to assess dietary intake during the week prior to stool
      sample collection. Fecal suspensions from 56 subjects were anaerobically
      incubated with quercetin and fecal microbiota composition was analyzed by next
      generation sequencing. Inter-individual variations in quercetin concentration and
      fecal microbiota composition at family level suggested differences in microbial
      quercetin metabolism. The abundance of Sutterellaceae (r = -0.292) and
      Oscillospiraceae (r = -0.334) was negatively correlated whereas that of
      Fusobacteriaceae (r = 0.361) and Enterobacteriaceae (r = 0.321) was positively
      correlated with quercetin concentration. Niacin (r = -0.313), vitamin B6 (r = 
      0.297), vitamin B12 (r = -0.266), vitamin D (r = -0.301), and ratio of animal
      protein to total protein (r = -0.27) were also negatively correlated with
      quercetin concentration. Bacterial abundance was positively or negatively related
      to intake of food components. This is the first report describing the
      relationship between fecal quercetin metabolism, human microbiota, and dietary
      intake in the elderly.

PMID- 29176867
TI  - Application of non-Gaussian water diffusional kurtosis imaging in the assessment
      of uterine tumors: A preliminary study.
AB  - OBJECTIVES: To evaluate the interobserver reliability and value of diffusional
      kurtosis imaging (DKI) in the assessment of uterine tumors compared with those of
      conventional diffusion-weighted imaging (DWI). METHODS: This retrospective study
      was approved by our institutional review board, which waived the requirement for
      informed consent. Fifty-eight women (mean age: 55.0 +/- 13.6 years; range: 30-89
      years) with suspected malignant uterine tumors underwent 3-T magnetic resonance
      imaging using DKI and DWI. Twelve had coexisting leiomyoma. Two observers
      analyzed region-of-interest measurements of diffusivity (D), kurtosis (K), and
      the apparent diffusion coefficient (ADC) of uterine lesions and healthy adjacent
      tissues. Interobserver agreement was evaluated using the intra-class correlation
      coefficient (ICC). The mean values were compared using one-way analysis of
      variance with a post-hoc Tukey's honestly significant difference test. The
      diagnostic accuracy of D and ADC in differentiating malignant tumors from benign
      leiomyomas was analyzed using receiver operating characteristic (ROC) analysis.
      RESULTS: The ICCs between the two observers in evaluating D, K, and the ADC of
      the malignant tumors were higher than 0.84, suggesting excellent interobserver
      agreements. The mean D (*10-3 mm2/s) of uterine cancers (1.05 +/- 0.41 and 1.09
      +/- 0.40 for observers 1 and 2, respectively) were significantly lower than those
      of leiomyoma (1.40 +/- 0.37 and 1.56 +/- 0.33, respectively; P < 0.05), healthy
      myometrium (1.72 +/- 0.27 and 1.69 +/- 0.30, respectively; P < 0.001), and
      healthy endometrium (1.53 +/- 0.35 and 1.42 +/- 0.37, respectively; P < 0.005).
      There was no significant difference in the area under the ROC curve between D and
      ADC. The mean K of uterine cancers (0.88 +/- 0.28 and 0.90 +/- 0.23,
      respectively) were higher than those of myometrium (0.72 +/- 0.10 and 0.73 +/-
      0.10, respectively; P < 0.001), healthy endometrium (0.65 +/- 0.13 and 0.60 +/-
      0.18, respectively; P < 0.001), and leiomyoma (0.76 +/- 0.14 and 0.77 +/- 0.16,
      respectively; not significant, P > 0.1). CONCLUSIONS: Interobserver agreements in
      evaluating D, K, and ADC were moderate to excellent. D performed equally to
      conventional DWI in differentiating between benign and malignant uterine lesions.
      The mean K of malignant uterine lesions was significantly higher than that of non
      tumorous myometrium or endometrium.

PMID- 29176868
TI  - A century of changing flows: Forest management changed flow magnitudes and
      warming advanced the timing of flow in a southwestern US river.
AB  - The continued provision of water from rivers in the southwestern United States to
      downstream cities, natural communities and species is at risk due to higher
      temperatures and drought conditions in recent decades. Snowpack and snowfall
      levels have declined, snowmelt and peak spring flows are arriving earlier, and
      summer flows have declined. Concurrent to climate change and variation, a century
      of fire suppression has resulted in dramatic changes to forest conditions, and
      yet, few studies have focused on determining the degree to which changing forests
      have altered flows. In this study, we evaluated changes in flow, climate, and
      forest conditions in the Salt River in central Arizona from 1914-2012 to compare
      and evaluate the effects of changing forest conditions and temperatures on flows.
      After using linear regression models to remove the influence of precipitation and
      temperature, we estimated that annual flows declined by 8-29% from 1914-1963,
      coincident with a 2-fold increase in basal area, a 2-3-fold increase in canopy
      cover, and at least a 10-fold increase in forest density within ponderosa pine
      forests. Streamflow volumes declined by 37-56% in summer and fall months during
      this period. Declines in climate-adjusted flows reversed at mid-century when
      spring and annual flows increased by 10-31% from 1964-2012, perhaps due to more
      winter rainfall. Additionally, peak spring flows occurred about 12 days earlier
      in this period than in the previous period, coincident with winter and spring
      temperatures that increased by 1-2 degrees C. While uncertainties remain, this
      study adds to the knowledge gained in other regions that forest change has had
      effects on flow that were on par with climate variability and, in the case of mid
      century declines, well before the influence of anthropogenic warming. Current
      large-scale forest restoration projects hold some promise of recovering seasonal
      flows.

PMID- 29176869
TI  - Successful transplantation of porcine liver grafts following 48-hour normothermic
      preservation.
AB  - Current cold storage organ preservation technique fails to preserve marginal
      donor grafts sufficiently. Evidence from large animal experiments suggests
      superiority of normothermic machine preservation of liver allografts. Long-term
      organ preservation using normothermic perfusion might not only allow organ
      viability assessment before transplantation, but also provide the means for
      further organ modifications under physiologic conditions. Previous research has
      shown that porcine livers can be transplanted successfully after normothermic
      preservation of 20 hours. In the present study we investigate whether similar
      methodology is capable of further extending the safe limit to 48 hours. In this
      study, livers from White Landrace pigs were preserved by normothermic, oxygenated
      sanguineous perfusion. After a 48-hour period of preservation, livers were
      transplanted into recipient pigs and followed for 5 days. Outcome parameters
      measured included markers of synthetic and metabolic liver function as well as
      hepatocellular injury and blood gas analysis during perfusion and follow-up.
      Histological assessment of morphological liver integrity was performed. All
      livers showed sustained bile production and metabolic activity throughout the
      preservation period. Low levels of hepatocellular damage were found. Following
      transplantation all liver grafts revealed excellent graft function and death
      censored graft survival was 100%. Porcine livers were transplanted successfully
      following 48 hours normothermic machine preservation.

PMID- 29176870
TI  - Molecular cloning, in-silico characterization and functional validation of
      monodehydroascorbate reductase gene in Eleusine coracana.
AB  - Ascorbic acid is a ubiquitous water soluble antioxidant that plays a critical
      role in plant growth and environmental stress tolerance. It acts as a free
      radical scavenger as well as a source of reducing power for several cellular
      processes. Because of its pivotal role in regulating plant growth under optimal
      as well as sub-optimal conditions, it becomes obligatory for plants to maintain a
      pool of reduced ascorbic acid. Several cellular processes help in maintaining the
      reduced ascorbic acid pool, by regulating its synthesis and regeneration
      processes. Current study demonstrates that monodehydroascorbate reductase is an
      important enzyme responsible for maintaining the reduced ascorbate pool, by
      optimizing the recycling of oxidized ascorbate. Cloning and functional
      characterization of this important stress inducible gene is of great significance
      for its imperative use in plant stress management. Therefore, we have cloned and
      functionally validated the role of monodehydroascorbate reductase gene (mdar)
      from a drought tolerant variety of Eleusine coracana. The cloned Ecmdar gene
      comprises of 1437bp CDS, encoding a 478 amino acid long polypeptide. The active
      site analysis showed presence of conserved Tyr348 residue, facilitating the
      catalytic activity in electron transfer mechanism. qPCR expression profiling of
      Ecmdar under stress indicated that it is an early responsive gene. The analysis
      of Ecmdar overexpressing Arabidopsis transgenic lines suggests that
      monodehydroascorbate reductase acts as a key stress regulator by modulating the
      activity of antioxidant enzymes to strengthen the ROS scavenging ability and
      maintains ROS homeostasis. Thus, it is evident that Ecmdar is an important gene
      for cellular homeostasis and its over-expression could be successfully used to
      strengthen stress tolerance in crop plants.

PMID- 29176871
TI  - Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in
      breast cancer patients.
AB  - Paraoxonase-1 (PON1) is an intra-cellular antioxidant enzyme found also in the
      circulation associated with high-density lipoproteins. The activity of this
      enzyme has been shown to be decreased in breast cancer (BC) patients. The aims of
      our study were to investigate the changes produced by radiotherapy (RT) on
      activity and concentration of serum PON1 in BC patients, and to evaluate the
      observed variations in relation to clinical and pathological characteristics of
      patients and tumors, and the response to treatment. We studied 200 women with BC
      who were scheduled to receive RT following excision of the tumor. Blood for
      analyses was obtained before and after the irradiation procedure. The control
      group was composed of 200 healthy women. Relative to control, BC patients had
      significantly lower serum PON1 activities pre-RT, while PON1 concentrations were
      at similar levels. RT was associated with a significant increase in serum PON1
      activities and concentrations. We observed significant differences in serum PON1
      concentrations post-RT between patients with luminal A or luminal B tumors. Serum
      PON1 concentration post-RT was markedly lower in BC patients with metastases. We
      conclude that benefit from RT accrues to the BC patients not only through its
      direct effect on cancer cells but also indirectly by improving the organism's
      anti-oxidant defense mechanisms. In addition, our preliminary evidence suggests
      that the measurement of serum PON1 concentration post-RT could be an efficient
      prognostic biomarker, and may be used as an index of the efficacy of the RT.

PMID- 29176873
TI  - Objective measurement of subjective tinnitus using the acoustic change complex.
AB  - At present, there is no objective method for diagnosing subjective sensorineural
      tinnitus. Recently, the acoustic change complex (ACC) has been used to evaluate
      neural detection of sounds. Thus, the present study aimed to examine whether the
      ACC can reflect cortical detection and discrimination of sounds matched with
      tinnitus frequencies. We hypothesized that the ACC to change stimuli matched with
      tinnitus frequencies would be decreased in tinnitus patients because the tinnitus
      interferes with the perception of acoustic changes. To test the hypothesis, 96
      ears of normal-hearing (NH) tinnitus patients and controls were tested. Among the
      tinnitus patients, 33 ears with a tinnitus frequency of 8 kHz constituted the
      tinnitus group, and the remaining 63 ears with no experience of tinnitus were
      allocated to the control group. For the 4 kHz non-tinnitus matched frequency, a
      subset of tinnitus (n = 17) and NH (n = 47) subjects was tested. The acoustic
      stimuli were pure tones with a total duration of 500 ms consisting of a 1 kHz
      tone in the first 250 ms and a second tone of either 8 kHz or 4 kHz in the latter
      250 ms. The normalized amplitude of the ACC (naACC) was calculated separately for
      the amplitude of the N1'-P2' complex evoked by an 8 kHz or 4 kHz change stimulus
      and for the amplitude of the N1-P2 complex elicited by the initial 1 kHz
      background stimulus. Our results showed that the naACC to an 8 kHz stimulus in
      the tinnitus group was significantly smaller than those to 4 kHz and 8 kHz in
      normal controls. Additionally, in the tinnitus group, the naACC to 4 kHz was
      greater compared to 8 kHz. The receiver operating characteristic (ROC) curve
      analysis conducted for naACC to 8 kHz at UCL revealed a fair degree of diagnostic
      efficacy. Overall, our results indicated that the ACC to a change stimulus
      matched with the tinnitus frequency can provide an objective measure of frequency
      specific tinnitus.

PMID- 29176872
TI  - Para-hydroxyphenylpyruvate inhibits the pro-inflammatory stimulation of
      macrophage preventing LPS-mediated nitro-oxidative unbalance and immunometabolic
      shift.
AB  - Targeting metabolism is emerging as a promising therapeutic strategy for
      modulation of the immune response in human diseases. In the presented study we
      used the lipopolysaccharide (LPS)-mediated activation of RAW 264.7 macrophage
      like cell line as a model to investigate changes in the metabolic phenotype and
      to test the effect of p-hydroxyphenylpyruvate (pHPP) on it. pHPP is an
      intermediate of the PHE/TYR catabolic pathway, selected as analogue of the ethyl
      pyruvate (EP), which proved to exhibit antioxidant and anti-inflammatory
      activities. The results obtained show that LPS-priming of RAW 264.7 cell line to
      the activated M1 state resulted in up-regulation of the inducible nitric oxide
      synthase (iNOS) expression and consequently of NO production and in release of
      the pro-inflammatory cytokine IL-6. All these effects were prevented dose
      dependently by mM concentrations of pHPP more efficiently than EP. Respirometric
      and metabolic flux analysis of LPS-treated RAW 264.7 cells unveiled a marked
      metabolic shift consisting in downregulation of the mitochondrial oxidative
      phosphorylation and upregulation of aerobic glycolysis respectively. The observed
      respiratory failure in LPS-treated cells was accompanied with inhibition of the
      respiratory chain complexes I and IV and enhanced production of reactive oxygen
      species. Inhibition of the respiratory activity was also observed following
      incubation of human neonatal fibroblasts (NHDF-neo) with sera from septic
      patients. pHPP prevented all the observed metabolic alteration caused by LPS on
      RAW 264.7 or by septic sera on NHDF-neo. Moreover, we provide evidence that pHPP
      is an efficient reductant of cytochrome c. On the basis of the presented results
      a working model, linking pathogen-associated molecular patterns (PAMPs)-mediated
      immune response to mitochondrial oxidative metabolism, is put forward along with
      suggestions for its therapeutic control.

PMID- 29176874
TI  - Neurturin overexpression in dopaminergic neurons induces presynaptic and
      postsynaptic structural changes in rats with chronic 6-hydroxydopamine lesion.
AB  - The structural effect of neurturin (NRTN) on the nigrostriatal dopaminergic
      system in animals remains unknown, although NRTN has been shown to be effective
      in Parkinson's disease animal models. Herein, we aimed to demonstrate that NRTN
      overexpression in dopaminergic neurons stimulates both neurite outgrowths in the
      nigrostriatal pathway and striatal dendritic spines in aging rats with chronic 6
      hydroxydopamine (6-OHDA) lesion. At week 12 after lesion, pTracer-mNRTN-His or
      pGreenLantern-1 plasmids were intranigrally transfected using the NTS-polyplex
      nanoparticles system. We showed that the transgenic expression in dopaminergic
      neurons remained until the end of the study (12 weeks). Only animals expressing
      NRTN-His showed recovery of tyrosine hydroxylase (TH)+ cells (28 +/- 2%), their
      neurites (32 +/- 2%) and the neuron-specific cytoskeletal marker beta-III-tubulin
      in the substantia nigra; striatal TH(+) fibers were also recovered (52 +/- 3%),
      when compared to the healthy condition. Neurotensin receptor type 1 levels were
      also significantly recovered in the substantia nigra and striatum. Dopamine
      recovery was 70 +/- 4% in the striatum and complete in the substantia nigra. The
      number of dendritic spines of striatal medium spiny neurons was also
      significantly increased, but the recovery was not complete. Drug-activated
      circling behavior decreased by 73 +/- 2% (methamphetamine) and 89 +/- 1%
      (apomorphine). Similar decrease was observed in the spontaneous motor behavior.
      Our results demonstrate that NRTN causes presynaptic and postsynaptic restoration
      of the nigrostriatal dopaminergic system after a 6-OHDA-induced chronic lesion.
      However, those improvements did not reach the healthy condition, suggesting that
      NRTN exerts lesser neurotrophic effects than other neurotrophic approaches.

PMID- 29176875
TI  - The orientation of homing pigeons (Columba livia f.d.) with and without
      navigational experience in a two-dimensional environment.
AB  - Homing pigeons are known for their excellent homing ability, and their brains
      seem to be functionally adapted to homing. It is known that pigeons with
      navigational experience show a larger hippocampus and also a more lateralised
      brain than pigeons without navigational experience. So we hypothesized that
      experience may have an influence also on orientation ability. We examined two
      groups of pigeons (11 with navigational experience and 17 without) in a standard
      operant chamber with a touch screen monitor showing a 2-D schematic of a
      rectangular environment (as "geometric" information) and one uniquely shaped and
      colored feature in each corner (as "landmark" information). Pigeons were trained
      first for pecking on one of these features and then we examined their ability to
      encode geometric and landmark information in four tests by modifying the
      rectangular environment. All tests were done under binocular and monocular
      viewing to test hemispheric dominance. The number of pecks was counted for
      analysis. Results show that generally both groups orientate on the basis of
      landmarks and the geometry of environment, but landmark information was
      preferred. Pigeons with navigational experience did not perform better on the
      tests but showed a better conjunction of the different kinds of information.
      Significant differences between monocular and binocular viewing were detected
      particularly in pigeons without navigational experience on two tests with reduced
      information. Our data suggest that the conjunction of geometric and landmark
      information might be integrated after processing separately in each hemisphere
      and that this process is influenced by experience.

PMID- 29176876
TI  - Neuroprotection and neuroregeneration of retinal ganglion cells after
      intravitreal carbon monoxide release.
AB  - PURPOSE: Retinal ischemia induces apoptosis leading to neurodegeneration and
      vision impairment. Carbon monoxide (CO) in gaseous form showed cell-protective
      and anti-inflammatory effects after retinal ischemia-reperfusion-injury (IRI).
      These effects were also demonstrated for the intravenously administered CO
      releasing molecule (CORM) ALF-186. This article summarizes the results of
      intravitreally released CO to assess its suitability as a neuroprotective and
      neuroregenerative agent. METHODS: Water-soluble CORM ALF-186 (25 MUg), PBS, or
      inactivated ALF (iALF) (all 5 MUl) were intravitreally applied into the left eyes
      of rats directly after retinal IRI for 1 h. Their right eyes remained unaffected
      and were used for comparison. Retinal tissue was harvested 24 h after
      intervention to analyze mRNA or protein expression of Caspase-3, pERK1/2, p38,
      HSP70/90, NF-kappaB, AIF-1 (allograft inflammatory factor), TNF-alpha, and GAP
      43. Densities of fluorogold-prelabeled retinal ganglion cells (RGC) were examined
      in flat-mounted retinae seven days after IRI and were expressed as mean/mm2. The
      ability of RGC to regenerate their axon was evaluated two and seven days after
      IRI using retinal explants in laminin-1-coated cultures. Immunohistochemistry was
      used to analyze the different cell types growing out of the retinal explants.
      RESULTS: Compared to the RGC-density in the contralateral right eyes (2804+/-214
      RGC/mm2; data are mean+/-SD), IRI+PBS injection resulted in a remarkable loss of
      RGC (1554+/-159 RGC/mm2), p<0.001. Intravitreally injected ALF-186 immediately
      after IRI provided RGC protection and reduced the extent of RGC-damage (IRI+PBS
      1554+/-159 vs. IRI+ALF 2179+/-286, p<0.001). ALF-186 increased the IRI-mediated
      phosphorylation of MAP-kinase p38. Anti-apoptotic and anti-inflammatory effects
      were detectable as Caspase-3, NF-kappaB, TNF-alpha, and AIF-1 expression were
      significantly reduced after IRI+ALF in comparison to IRI+PBS or IRI+iALF. Gap-43
      expression was significantly increased after IRI+ALF. iALF showed effects similar
      to PBS. The intrinsic regenerative potential of RGC-axons was induced to nearly
      identical levels after IRI and ALF or iALF-treatment under growth-permissive
      conditions, although RGC viability differed significantly in both groups.
      Intravitreal CO further increased the IRI-induced migration of GFAP-positive
      cells out of retinal explants and their transdifferentiation, which was detected
      by re-expression of beta-III tubulin and nestin. CONCLUSION: Intravitreal CORM
      ALF-186 protected RGC after IRI and stimulated their axons to regenerate in
      vitro. ALF conveyed anti-apoptotic, anti-inflammatory, and growth-associated
      signaling after IRI. CO's role in neuroregeneration and its effect on retinal
      glial cells needs further investigation.

PMID- 29176877
TI  - Rv0004 is a new essential member of the mycobacterial DNA replication machinery.
AB  - DNA replication is fundamental for life, yet a detailed understanding of
      bacterial DNA replication is limited outside the organisms Escherichia coli and
      Bacillus subtilis. Many bacteria, including mycobacteria, encode no identified
      homologs of helicase loaders or regulators of the initiator protein DnaA, despite
      these factors being essential for DNA replication in E. coli and B. subtilis. In
      this study we discover that a previously uncharacterized protein, Rv0004, from
      the human pathogen Mycobacterium tuberculosis is essential for bacterial
      viability and that depletion of Rv0004 leads to a block in cell cycle
      progression. Using a combination of genetic and biochemical approaches, we found
      that Rv0004 has a role in DNA replication, interacts with DNA and the replicative
      helicase DnaB, and affects DnaB-DnaA complex formation. We also identify a
      conserved domain in Rv0004 that is predicted to structurally resemble the N
      terminal protein-protein interaction domain of DnaA. Mutation of a single
      conserved tryptophan within Rv0004's DnaA N-terminal-like domain leads to
      phenotypes similar to those observed upon Rv0004 depletion and can affect the
      association of Rv0004 with DnaB. In addition, using live cell imaging during
      depletion of Rv0004, we have uncovered a previously unappreciated role for DNA
      replication in coordinating mycobacterial cell division and cell size. Together,
      our data support that Rv0004 encodes a homolog of the recently identified DciA
      family of proteins found in most bacteria that lack the DnaC-DnaI helicase
      loaders in E. coli and B. subtilis. Therefore, the mechanisms of Rv0004
      elucidated here likely apply to other DciA homologs and reveal insight into the
      diversity of bacterial strategies in even the most conserved biological
      processes.

PMID- 29176878
TI  - Genome-wide recombination rate variation in a recombination map of cotton.
AB  - Recombination is crucial for genetic evolution, which not only provides new
      allele combinations but also influences the biological evolution and efficacy of
      natural selection. However, recombination variation is not well understood
      outside of the complex species' genomes, and it is particularly unclear in
      Gossypium. Cotton is the most important natural fibre crop and the second largest
      oil-seed crop. Here, we found that the genetic and physical maps distances did
      not have a simple linear relationship. Recombination rates were unevenly
      distributed throughout the cotton genome, which showed marked changes along the
      chromosome lengths and recombination was completely suppressed in the centromeric
      regions. Recombination rates significantly varied between A-subgenome (At) (range
      = 1.60 to 3.26 centimorgan/megabase [cM/Mb]) and D-subgenome (Dt) (range = 2.17
      to 4.97 cM/Mb), which explained why the genetic maps of At and Dt are similar but
      the physical map of Dt is only half that of At. The translocation regions between
      A02 and A03 and between A04 and A05, and the inversion regions on A10, D10, A07
      and D07 indicated relatively high recombination rates in the distal regions of
      the chromosomes. Recombination rates were positively correlated with the
      densities of genes, markers and the distance from the centromere, and negatively
      correlated with transposable elements (TEs). The gene ontology (GO) categories
      showed that genes in high recombination regions may tend to response to
      environmental stimuli, and genes in low recombination regions are related to
      mitosis and meiosis, which suggested that they may provide the primary driving
      force in adaptive evolution and assure the stability of basic cell cycle in a
      rapidly changing environment. Global knowledge of recombination rates will
      facilitate genetics and breeding in cotton.

PMID- 29176879
TI  - Socio-demographic predictors of health and environmental co-benefit behaviours
      for climate change mitigation in urban China.
AB  - OBJECTIVE: This study aims to examine the patterns and socio-demographic
      predictors of health and environmental co-benefit behaviours that support climate
      change mitigation in a densely populated Asian metropolis-Hong Kong. METHODS: A
      population-based, stratified and cross-sectional random digit dialling telephone
      survey study was conducted between January and February 2016, among the Cantonese
      speaking population aged 15 and above in Hong Kong. Socio-demographic data and
      the self-reported practice of 10 different co-benefit behaviours were solicited.
      Ethics approval and participant's verbal consent were sought. FINDINGS: The study
      sample consisted of 1,017 respondents (response rate: 63.6%) were comparable to
      the age, gender and geographical distributions of the Hong Kong population found
      in the latest 2011 Hong Kong Population Census. Among the co-benefit behaviours,
      using less packaging and disposable shopping bags were practiced in the highest
      frequency (70.1%). However, four behaviours were found to have never been
      practiced by more than half of the respondents, including bringing personal
      eating utensils when dining in restaurants or small eateries, showering less than
      five minutes, having one vegetarian meal a week, and buying more organic food.
      Results of multivariable logistic regression showed that frequency of practicing
      co-benefit behaviours were consistently associated with gender and age.
      CONCLUSION: Urban residents in Hong Kong do not engage in the practice of co
      benefit behaviours in a uniform way. In general, females and older people are
      more likely to adopt co-benefit behaviours in their daily lives. Further research
      to assess the knowledge and attitudes of the population towards these co-benefit
      behaviours will provide support to relevant climate change mitigation policies
      and education programmes.

PMID- 29176880
TI  - Seroprevalence of rickettsial infections and Q fever in Bhutan.
AB  - BACKGROUND: With few studies conducted to date, very little is known about the
      epidemiology of rickettsioses in Bhutan. Due to two previous outbreaks and
      increasing clinical cases, scrub typhus is better recognized than other
      rickettsial infections and Q fever. METHODOLOGY: A descriptive cross-sectional
      serosurvey was conducted from January to March 2015 in eight districts of Bhutan.
      Participants were 864 healthy individuals from an urban (30%) and a rural (70%)
      sampling unit in each of the eight districts. Serum samples were tested by
      microimmunofluorescence assay for rickettsial antibodies at the Australian
      Rickettsial Reference Laboratory. RESULTS: Of the 864 participants, 345 (39.9%)
      were males and the mean age of participants was 41.1 (range 13-98) years. An
      overall seroprevalence of 49% against rickettsioses was detected. Seroprevalence
      was highest against scrub typhus group (STG) (22.6%) followed by spotted fever
      group (SFG) rickettsia (15.7%), Q fever (QF) (6.9%) and typhus group (TG)
      rickettsia (3.5%). Evidence of exposure to multiple agents was also noted; the
      commonest being dual exposure to STG and SFG at 5%. A person's likelihood of
      exposure to STG and SFG rickettsia significantly increased with age and farmers
      were twice as likely to have evidence of STG exposure as other occupations.
      Trongsa district appeared to be a hotspot for STG exposure while Punakha district
      had the lowest STG exposure risk. Zhemgang had the lowest exposure risk to SFG
      rickettsia compared to other districts. People living at altitudes above 2000
      meters were relatively protected from STG infections but this was not observed
      for SFG, TG or QF exposure. CONCLUSION: This seroprevalence study highlights the
      endemicity of STG and SFG rickettsia in Bhutan. The high seroprevalence warrants
      appropriate public health interventions, such as diagnostic improvements and
      clinical treatment guidelines. Future studies should focus on vector profiles,
      geospatial, bio-social and environmental risk assessment and preventive and
      control strategies.

PMID- 29176881
TI  - A novel registration-based methodology for prediction of trabecular bone fabric
      from clinical QCT: A comprehensive analysis.
AB  - Osteoporosis leads to hip fractures in aging populations and is diagnosed by
      modern medical imaging techniques such as quantitative computed tomography (QCT).
      Hip fracture sites involve trabecular bone, whose strength is determined by
      volume fraction and orientation, known as fabric. However, bone fabric cannot be
      reliably assessed in clinical QCT images of proximal femur. Accordingly, we
      propose a novel registration-based estimation of bone fabric designed to preserve
      tensor properties of bone fabric and to map bone fabric by a global and local
      decomposition of the gradient of a non-rigid image registration transformation.
      Furthermore, no comprehensive analysis on the critical components of this
      methodology has been previously conducted. Hence, the aim of this work was to
      identify the best registration-based strategy to assign bone fabric to the QCT
      image of a patient's proximal femur. The normalized correlation coefficient and
      curvature-based regularization were used for image-based registration and the
      Frobenius norm of the stretch tensor of the local gradient was selected to
      quantify the distance among the proximal femora in the population. Based on this
      distance, closest, farthest and mean femora with a distinction of sex were chosen
      as alternative atlases to evaluate their influence on bone fabric prediction.
      Second, we analyzed different tensor mapping schemes for bone fabric prediction:
      identity, rotation-only, rotation and stretch tensor. Third, we investigated the
      use of a population average fabric atlas. A leave one out (LOO) evaluation study
      was performed with a dual QCT and HR-pQCT database of 36 pairs of human femora.
      The quality of the fabric prediction was assessed with three metrics, the tensor
      norm (TN) error, the degree of anisotropy (DA) error and the angular deviation of
      the principal tensor direction (PTD). The closest femur atlas (CTP) with a full
      rotation (CR) for fabric mapping delivered the best results with a TN error of
      7.3 +/- 0.9%, a DA error of 6.6 +/- 1.3% and a PTD error of 25 +/- 2 degrees .
      The closest to the population mean femur atlas (MTP) using the same mapping
      scheme yielded only slightly higher errors than CTP for substantially less
      computing efforts. The population average fabric atlas yielded substantially
      higher errors than the MTP with the CR mapping scheme. Accounting for sex did not
      bring any significant improvements. The identified fabric mapping methodology
      will be exploited in patient-specific QCT-based finite element analysis of the
      proximal femur to improve the prediction of hip fracture risk.

PMID- 29176882
TI  - Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen
      protein interactions.
AB  - Coxiella burnetii is an obligate Gram-negative intracellular pathogen and the
      etiological agent of Q fever. Successful infection requires a functional Type IV
      secretion system, which translocates more than 100 effector proteins into the
      host cytosol to establish the infection, restructure the intracellular host
      environment, and create a parasitophorous vacuole where the replicating bacteria
      reside. We used yeast two-hybrid (Y2H) screening of 33 selected C. burnetii
      effectors against whole genome human and murine proteome libraries to generate a
      map of potential host-pathogen protein-protein interactions (PPIs). We detected
      273 unique interactions between 20 pathogen and 247 human proteins, and 157
      between 17 pathogen and 137 murine proteins. We used orthology to combine the
      data and create a single host-pathogen interaction network containing 415 unique
      interactions between 25 C. burnetii and 363 human proteins. We further performed
      complementary pairwise Y2H testing of 43 out of 91 C. burnetii-human interactions
      involving five pathogen proteins. We used the combined data to 1) perform
      enrichment analyses of target host cellular processes and pathways, 2) examine
      effectors with known infection phenotypes, and 3) infer potential mechanisms of
      action for four effectors with uncharacterized functions. The host-pathogen
      interaction profiles supported known Coxiella phenotypes, such as adapting cell
      morphology through cytoskeletal re-arrangements, protein processing and
      trafficking, organelle generation, cholesterol processing, innate immune
      modulation, and interactions with the ubiquitin and proteasome pathways. The
      generated dataset of PPIs-the largest collection of unbiased Coxiella host
      pathogen interactions to date-represents a rich source of information with
      respect to secreted pathogen effector proteins and their interactions with human
      host proteins.

PMID- 29176883
TI  - Wnt co-receptors Lrp5 and Lrp6 differentially mediate Wnt3a signaling in
      osteoblasts.
AB  - Wnt3a is a major regulator of bone metabolism however, very few of its target
      genes are known in bone. Wnt3a preferentially signals through transmembrane
      receptors Frizzled and co-receptors Lrp5/6 to activate the canonical signaling
      pathway. Previous studies have shown that the canonical Wnt co-receptors Lrp5 and
      Lrp6 also play an essential role in normal postnatal bone homeostasis, yet, very
      little is known about specific contributions by these co-receptors in Wnt3a
      dependent signaling. We used high-throughput sequencing technology to identify
      target genes regulated by Wnt3a in osteoblasts and to elucidate the role of Lrp5
      and Lrp6 in mediating Wnt3a signaling. Our study identified 782 genes regulated
      by Wnt3a in primary calvarial osteoblasts. Wnt3a up-regulated the expression of
      several key regulators of osteoblast proliferation/ early stages of
      differentiation while inhibiting genes expressed in later stages of
      osteoblastogenesis. We also found that Lrp6 is the key mediator of Wnt3a
      signaling in osteoblasts and Lrp5 played a less significant role in mediating
      Wnt3a signaling.

PMID- 29176884
TI  - Alcohol consumption and risk of uterine myoma: A systematic review and meta
      analysis.
AB  - BACKGROUND: The published data about alcohol consumption and uterine myoma are
      scanty and controversial: some studies found positive association whereas other
      studies showed no association. OBJECTIVES: To conduct a systematic review and
      meta-analysis to determine whether alcohol is a risk factor for myoma. SEARCH
      STRATEGY: A MEDLINE/EMBASE search was carried out, supplemented by manual
      searches of bibliographies of the selected studies. SELECTION CRITERIA: Articles
      published as full-length papers in English. In the review we included all
      identified studies. Otherwise, the inclusion criteria for studies included in the
      meta-analysis were: a) case-control or cohort studies, reporting original data;
      b) studies reporting original data on the association between alcohol consumption
      and myoma; c) diagnosis of myoma was ultrasound or histological confirmed and/or
      clinically based. DATA COLLECTION AND ANALYSIS: A total of 6 studies were
      identified for the review and 5 studies were included in the meta-analysis. The
      primary outcome was the incidence of uterine myoma in ever versus never alcohol
      drinkers and when data were available, we also analyzed categories of alcohol
      intake. We assessed the outcomes in the overall population and then we performed
      a subgroup analysis according to study design. Pooled estimates of the odds
      ratios (OR) with 95% confidence interval (CI) were calculated using random
      effects models. MAIN RESULTS: The summary OR (95%CI) of myoma forever versus
      never alcohol intake was 1.12 (0.94-1.34) with significant heterogeneity. The
      summary OR for current versus never drinking was 1.33 (1.01-1.76) with no
      heterogeneity. CONCLUSIONS: Ever alcohol consumption is not associated with myoma
      risk. Based on the data of two studies, current alcohol drinkers had a slightly
      borderline increased risk of diagnosis of myoma. In consideration of the very
      limited number of studies and the suggestion of a potential increased risk among
      current drinkers, further studies are required.

PMID- 29176885
TI  - Evaluation of myocardial glucose metabolism in hypertrophic cardiomyopathy using
      18F-fluorodeoxyglucose positron emission tomography.
AB  - BACKGROUND: The purposes of this study were to assess the usefulness of
      myocardial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography
      (PET)/computed tomography (CT) for evaluating myocardial metabolic status in
      hypertrophic cardiomyopathy (HCM) and the therapeutic efficacy of alcohol septal
      ablation (ASA) in hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Thirty
      HCM patients (64.4+/-10.5 years, 14 male, 12 hypertrophic non-obstructive
      cardiomyopathy [HNCM], 16 HOCM, and 2 dilated phase of HCM) underwent 18F-FDG
      PET/CT. 18F-FDG uptake was semi-quantitatively evaluated using an uptake score in
      each 17 segment and the entire LV or regional standardized uptake value (SUV).
      RESULTS: 18F-FDG uptake was observed mostly in a hypertrophied myocardium in HNCM
      patients, whereas 18F-FDG was extensively accumulated beyond the hypertrophied
      myocardium in HOCM patients. There was a positive correlation between the summed
      uptake score of 18F-FDG and high-sensitive troponin T level in HNCM patients (r =
      0.603, p = 0.049), whereas the score was positively correlated with brain
      natriuretic peptide level (r = 0.614, p = 0.011) in HOCM patients. In 10 patients
      who received ASA, the maximum SUV of the entire LV was significantly reduced from
      5.6+/-2.6 to 3.2+/-2.1 (p = 0.040) after ASA. Reduction of that maximum SUV was
      particularly significant in the lateral region (from 5.5+/-2.6 to 2.9 +/-2.2, p =
      0.024) but not significant in the anteroseptal region (from 4.5+/-2.6 to 2.9+/
      1.6, p = 0.12). CONCLUSION: Extensive 18F-FDG uptake beyond the hypertrophied
      myocardium was observed in HOCM. ASA attenuates 18F-FDG uptake in a remote
      lateral myocardium.

PMID- 29176886
TI  - Differences in phonetic discrimination stem from differences in psychoacoustic
      abilities in learning the sounds of a second language: Evidence from ERP
      research.
AB  - The scientific community has been divided as to the origin of individual
      differences in perceiving the sounds of a second language (L2). There are two
      alternative explanations: a general psychoacoustic origin vs. a speech-specific
      one. A previous study showed that such individual variability is linked to the
      perceivers' speech-specific capabilities, rather than the perceivers'
      psychoacoustic abilities. However, we assume that the selection of participants
      and parameters of sound stimuli might not appropriate. Therefore, we adjusted the
      sound stimuli and recorded event-related potentials (ERPs) from two groups of
      early, proficient Cantonese (L1)-Mandarin (L2) bilinguals who differed in their
      mastery of the Mandarin (L2) phonetic contrast /in-ing/, to explore whether the
      individual differences in perceiving L2 stem from participants' ability to
      discriminate various pure tones (frequency, duration and pattern). To precisely
      measure the participants' acoustic discrimination, mismatch negativity (MMN)
      elicited by the oddball paradigm was recorded in the experiment. The results
      showed that significant differences between good perceivers (GPs) and poor
      perceivers (PPs) were found in the three general acoustic conditions (frequency,
      duration and pattern), and the MMN amplitude for GP was significantly larger than
      for PP. Therefore, our results support a general psychoacoustic origin of
      individual variability in L2 phonetic mastery.

PMID- 29176887
TI  - First external quality assurance program for bloodstream Real-Time PCR monitoring
      of treatment response in clinical trials of Chagas disease.
AB  - Real-Time PCR (qPCR) testing is recommended as both a diagnostic and outcome
      measurement of etiological treatment in clinical practice and clinical trials of
      Chagas disease (CD), but no external quality assurance (EQA) program provides
      performance assessment of the assays in use. We implemented an EQA system to
      evaluate the performance of molecular biology laboratories involved in qPCR based
      follow-up in clinical trials of CD. An EQA program was devised for three clinical
      trials of CD: the E1224 (NCT01489228), a pro-drug of ravuconazole; the Sampling
      Study (NCT01678599), that used benznidazole, both conducted in Bolivia; and the
      CHAGASAZOL (NCT01162967), that tested posaconazole, conducted in Spain. Four
      proficiency testing panels containing negative controls and seronegative blood
      samples spiked with 1, 10 and 100 parasite equivalents (par. eq.)/mL of four
      Trypanosoma cruzi stocks, were sent from the Core Lab in Argentina to the
      participating laboratories located in Bolivia and Spain. Panels were analyzed
      simultaneously, blinded to sample allocation, at 4-month intervals. In addition,
      302 random blood samples from both trials carried out in Bolivia were sent to
      Core Lab for retesting analysis. The analysis of proficiency testing panels gave
      100% of accordance (within laboratory agreement) and concordance (between
      laboratory agreement) for all T. cruzi stocks at 100 par. eq./mL; whereas their
      values ranged from 71 to 100% and from 62 to 100% at 1 and 10 par. eq./mL,
      respectively, depending on the T. cruzi stock. The results obtained after twelve
      months of preparation confirmed the stability of blood samples in guanidine-EDTA
      buffer. No significant differences were found between qPCR results from Bolivian
      laboratory and Core Lab for retested clinical samples. This EQA program for qPCR
      analysis of CD patient samples may significantly contribute to ensuring the
      quality of laboratory data generated in clinical trials and molecular diagnostics
      laboratories of CD.

PMID- 29176888
TI  - Measuring the extent of overlaps in protected area designations.
AB  - Over the past decades, a number of national policies and international
      conventions have been implemented to promote the expansion of the world's
      protected area network, leading to a diversification of protected area
      strategies, types and designations. As a result, many areas are protected by more
      than one convention, legal instrument, or other effective means which may result
      in a lack of clarity around the governance and management regimes of particular
      locations. We assess the degree to which different designations overlap at
      global, regional and national levels to understand the extent of this phenomenon
      at different scales. We then compare the distribution and coverage of these multi
      designated areas in the terrestrial and marine realms at the global level and
      among different regions, and we present the percentage of each county's protected
      area extent that is under more than one designation. Our findings show that
      almost a quarter of the world's protected area network is protected through more
      than one designation. In fact, we have documented up to eight overlapping
      designations. These overlaps in protected area designations occur in every region
      of the world, both in the terrestrial and marine realms, but are more common in
      the terrestrial realm and in some regions, notably Europe. In the terrestrial
      realm, the most common overlap is between one national and one international
      designation. In the marine realm, the most common overlap is between any two
      national designations. Multi-designations are therefore a widespread phenomenon
      but its implications are not well understood. This analysis identifies, for the
      first time, multi-designated areas across all designation types. This is a key
      step to understand how these areas are managed and governed to then move towards
      integrated and collaborative approaches that consider the different management
      and conservation objectives of each designation.

PMID- 29176889
TI  - All-cause mortality among diabetic foot patients and related risk factors in
      Saudi Arabia.
AB  - BACKGROUND: Although Diabetes mellitus is a major public health problem in the
      Middle East and North Africa (MENA) region with high rates of diabetic foot
      complications, there are only limited data concerning mortality among such a high
      risk group. Therefore, the main aim of the current study was to assess all-cause
      mortality and its related predictors among diabetic patients with and without
      diabetic foot complications. METHODS: Using data from the Saudi National Diabetes
      Registry (SNDR), a total of 840 patients with type 1 or type 2 diabetes aged >=25
      years with current or past history of diabetic foot ulcer (DFU) or diabetes
      related lower extremity amputation (LEA) were recruited in 2007 from active
      patients' files and followed up to 2013. These patients were compared with an
      equal number of age and gender matched diabetic patients without foot
      complication recruited at the same period. All patients were subjected to living
      status verification at 31st December 2013. RESULTS: The all-cause mortality rate
      among patients with DFU was 42.54 per 1000 person-years and among LEA patients
      was 86.80 per 1000 person-years among LEA patients for a total of 2280 and 1129
      person-years of follow up respectively. The standardized mortality ratio (SMR)
      (95% CI) was 4.39 (3.55-5.23) and 7.21 (5.70-8.72) for cases with foot ulcer and
      LEA respectively. The percentage of deceased patients increased by almost twofold
      (18.5%) among patients with diabetic foot ulcer and more than threefold (32.2%)
      among patients with LEA compared with patients without diabetic foot
      complications (10.7%). The worst survival was among patients with LEA at 0.679
      and the presence of diabetic nephropathy was the only significant independent
      risk factor for all-cause mortality among patients with diabetic foot
      complications. On the other hand, obese patients have demonstrated significantly
      reduced all-cause mortality rate. CONCLUSIONS: Diabetic patients with diabetic
      foot complications have an excess mortality rate when compared with diabetic
      counterparts without foot complications and the general population. Early
      interventions to prevent foot ulceration and consequent LEA as well as all the
      measurements for reducing the prevalence of microvascular and macrovascular
      complications should be considered.

PMID- 29176890
TI  - Persistent abnormalities in pulmonary arterial compliance after heart
      transplantation in patients with combined post-capillary and pre-capillary
      pulmonary hypertension.
AB  - BACKGROUND: The hemodynamic definitions of pulmonary hypertension (PH) in left
      heart disease have recently been refined to better match the characteristics
      required to reflect the presence of pulmonary vascular disease. Accordingly, we
      tested the hypothesis that abnormalities in the stiffness of pulmonary
      circulation would persist after heart transplantation in patients with combined
      post-capillary and pre-capillary PH (Cpc-PH) in contrast to those with isolated
      post-capillary PH (Ipc-PH). METHODS: We retrospectively analyzed right heart
      hemodynamics in a cohort of 295 consecutive patients with heart failure and
      advanced left ventricular systolic dysfunction (LVSD) before and 1 year after
      heart transplantation. RESULTS: According to their baseline hemodynamic profile,
      patients were classified as: 75 Cpc-PH, 111 Ipc-PH, and 98 without PH (no-PH),
      and 11 pre-capillary PH. One year after heart transplantation, pulmonary artery
      pressures, pulmonary vascular resistance and cardiac index normalized in all
      patients regardless of the baseline hemodynamic profile. However, pulmonary
      arterial compliance remained lower in Cpc-PH patients (from 1.6+/-1.2 at baseline
      to 3.7+/-1.4 ml/mmHg at 1 year) than in Ipc-PH (from 1.2+/-2.0 to 4.4+/-2.3
      ml/mmHg) and no-PH patients (from 3.7+/-2.0 to 4.5+/-1.8 ml/mmHg); (adjusted p =
      0.03 Ipc-PH vs. Cpc-PH INT<0.001). CONCLUSIONS: In heart failure patients with
      advanced LVSD, a hemodynamic profile characterized by Cpc-PH predicts the
      persistence of a stiffer pulmonary circulation at 1 year after heart
      transplantation.

PMID- 29176891
TI  - Quantitative proteomic analysis of amastigotes from Leishmania (L.) amazonensis
      LV79 and PH8 strains reveals molecular traits associated with the virulence
      phenotype.
AB  - BACKGROUND: Leishmaniasis is an antropozoonosis caused by Leishmania parasites
      that affects around 12 million people in 98 different countries. The disease has
      different clinical forms, which depend mainly on the parasite genetics and on the
      immunologic status of the host. The promastigote form of the parasite is
      transmitted by an infected female phlebotomine sand fly, is internalized by
      phagocytic cells, mainly macrophages, and converts into amastigotes which
      replicate inside these cells. Macrophages are important cells of the immune
      system, capable of efficiently killing intracellular pathogens. However,
      Leishmania can evade these mechanisms due to expression of virulence factors.
      Different strains of the same Leishmania species may have different infectivity
      and metastatic phenotypes in vivo, and we have previously shown that analysis of
      amastigote proteome can give important information on parasite infectivity.
      Differential abundance of virulence factors probably accounts for the higher
      virulence of PH8 strain parasites shown in this work. In order to test this
      hypothesis, we have quantitatively compared the proteomes of PH8 and LV79 lesion
      derived amastigotes using a label-free proteomic approach. METHODOLOGY/PRINCIPAL
      FINDINGS: In the present work, we have compared lesion development by L. (L.)
      amazonensis PH8 and LV79 strains in mice, showing that they have different
      virulence in vivo. Viability and numbers of lesion-derived amastigotes were
      accordingly significantly different. Proteome profiles can discriminate parasites
      from the two strains and several proteins were differentially expressed.
      CONCLUSIONS/SIGNIFICANCE: This work shows that PH8 strain is more virulent in
      mice, and that lesion-derived parasites from this strain are more viable and more
      infective in vitro. Amastigote proteome comparison identified GP63 as highly
      expressed in PH8 strain, and Superoxide Dismutase, Tryparedoxin Peroxidase and
      Heat Shock Protein 70 as more abundant in LV79 strain. The expression profile of
      all proteins and of the differential ones precisely classified PH8 and LV79
      samples, indicating that the two strains have proteins with different abundances
      and that proteome profiles correlate with their phenotypes.

PMID- 29176892
TI  - Tobacco consumption and nicotine dependence in Bengo Province, Angola: A
      community-based survey.
AB  - There is concern about the potentially increasing use of tobacco in Angola.
      However, information on the frequency and determinants of this use is not
      systematised. This study aimed to estimate the prevalence of tobacco consumption
      and nicotine dependence among smokers in an Angolan population and considering
      individual socio-demographic and behavioural characteristics. A community-based
      survey with 2,472 respondents (age range: 15-64 years) was conducted in 2013-2014
      in the country's Bengo Province. The collection methodology for assessing each
      type of tobacco consumption and its daily quantification followed the World
      Health Organization STEPwise approach to chronic disease risk factor
      surveillance. The Fagerstrom Test for Nicotine Dependence was also used to assess
      smokers. Mean values for prevalence of tobacco use and nicotine dependence were
      estimated by sex and by previously defined variables. Daily smoking (6.1%) was
      found to be higher for males (10.0%) them among females (2.6%), and the amount of
      ex-smokers (7.5%) was higher them smokers. Only 0.2% of those surveyed reported
      use of smokeless (chewing) tobacco. One-third of ever-smokers reported having
      started smoking daily before age 18. Nicotine dependence levels were classified
      as very low or low in 83.6% of the smokers. Daily smoking prevalence increased
      with age, and was higher in rural areas and among individuals with no formal
      education, lower incomes, and alcohol consumption. This population presented a
      low smoking prevalence, along with a low number of daily smoked cigarettes and
      low levels of nicotine dependency, despite the low prices of, and easy access to,
      manufactured cigarettes. These two factors conjugated with the current absence of
      an Angolan policy for tobacco control, enhance the susceptibility for rising
      overall tobacco use in the near future.

PMID- 29176893
TI  - The fear of being laughed at as additional diagnostic criterion in social anxiety
      disorder and avoidant personality disorder?
AB  - Social anxiety disorder (SAD) is the most common anxiety disorder and has
      considerable negative impact on social functioning, quality of life, and career
      progression of those affected. Gelotophobia (the fear of being laughed at) shares
      many similarities and has therefore been proposed as a subtype of SAD. This
      hypothesis has, however, never been tested in a clinical sample. Thus, the
      relationship between gelotophobia, SAD and avoidant personality disorder (APD)
      was investigated by examining a sample of 133 participants (64 psychiatric
      patients and 69 healthy controls matched for age and sex) using the Structured
      Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders
      (4th edition) and an established rating instrument for gelotophobia (GELOPH<15>).
      As expected, gelotophobia scores and the number of gelotophobic individuals were
      significantly higher among patients with SAD (n = 22) and APD (n = 12) compared
      to healthy controls and other psychiatric patients. Furthermore, gelotophobia
      scores were highest in patients suffering from both SAD and APD. In fact, all
      patients suffering from both disorders were also suffering from gelotophobia. As
      explained in the discussion, the observed data did not suggest that gelotophobia
      is a subtype of SAD. The findings rather imply that the fear of being laughed at
      is a symptom characteristic for both SAD and APD. Based on that, gelotophobia may
      prove to be a valuable additional diagnostic criterion for SAD and APD and the
      present results also contribute to the ongoing debate on the relationship between
      SAD and APD.

PMID- 29176894
TI  - Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis
      pathway contributed to Mycobacterium tuberculosis pathoadaptation.
AB  - The unique ability of the tuberculosis (TB) bacillus, Mycobacterium tuberculosis,
      to persist for long periods of time in lung hypoxic lesions chiefly contributes
      to the global burden of latent TB. We and others previously reported that the M.
      tuberculosis ancestor underwent massive episodes of horizontal gene transfer
      (HGT), mostly from environmental species. Here, we sought to explore whether such
      ancient HGT played a part in M. tuberculosis evolution towards pathogenicity. We
      were interested by a HGT-acquired M. tuberculosis-specific gene set, namely moaA1
      D1, which is involved in the biosynthesis of the molybdenum cofactor. Horizontal
      acquisition of this gene set was striking because homologues of these moa genes
      are present all across the Mycobacterium genus, including in M. tuberculosis.
      Here, we discovered that, unlike their paralogues, the moaA1-D1 genes are
      strongly induced under hypoxia. In vitro, a M. tuberculosis moaA1-D1-null mutant
      has an impaired ability to respire nitrate, to enter dormancy and to survive in
      oxygen-limiting conditions. Conversely, heterologous expression of moaA1-D1 in
      the phylogenetically closest non-TB mycobacterium, Mycobacterium kansasii, which
      lacks these genes, improves its capacity to respire nitrate and grants it with a
      marked ability to survive oxygen depletion. In vivo, the M. tuberculosis moaA1-D1
      null mutant shows impaired survival in hypoxic granulomas in C3HeB/FeJ mice, but
      not in normoxic lesions in C57BL/6 animals. Collectively, our results identify a
      novel pathway required for M. tuberculosis resistance to host-imposed stress,
      namely hypoxia, and provide evidence that ancient HGT bolstered M. tuberculosis
      evolution from an environmental species towards a pervasive human-adapted
      pathogen.

PMID- 29176895
TI  - Functional connectivity analysis of distracted drivers based on the wavelet phase
      coherence of functional near-infrared spectroscopy signals.
AB  - The present study aimed to evaluate the functional connectivity (FC) in relevant
      cortex areas during simulated driving with distraction based on functional near
      infrared spectroscopy (fNIRS) method. Twelve subjects were recruited to perform
      three types of driving tasks, namely, straight driving, straight driving with
      secondary auditory task, and straight driving with secondary visual vigilance
      task, on a driving simulator. The wavelet amplitude (WA) and wavelet phase
      coherence (WPCO) of the fNIRS signals were calculated in six frequency intervals:
      I, 0.6-2 Hz; II, 0.145-0.6 Hz; III, 0.052-0.145 Hz; IV, 0.021-0.052 Hz; and V,
      0.0095-0.021 Hz, VI, 0.005-0.0095Hz. Results showed that secondary tasks during
      driving led to worse driving performance, brain activity changes, and dynamic
      configuration of the connectivity. The significantly lower WA value in the right
      motor cortex in interval IV, and higher WPCO values in intervals II, V, and VI
      were found with additional auditory task. Significant standard deviation of speed
      and lower WA values in the left prefrontal cortex and right prefrontal cortex in
      interval VI, and lower WPCO values in intervals I, IV, V, and VI were found under
      the additional visual vigilance task. The results suggest that the changed FC
      levels in intervals IV, V, and VI were more likely to reflect the driver's
      distraction condition. The present study provides new insights into the
      relationship between distracted driving behavior and brain activity. The method
      may be used for the evaluation of drivers' attention level.

PMID- 29176896
TI  - Aging-related limit of exercise efficacy on motor decline.
AB  - Identifying lifestyle strategies and allied neurobiological mechanisms that
      reduce aging-related motor impairment is imperative, given the accelerating
      number of retirees and increased life expectancy. A physically active lifestyle
      prior to old age can reduce risk of debilitating motor decline. However, if
      exercise is initiated after motor decline has begun in the lifespan, it is
      unknown if aging itself may impose a limit on exercise efficacy to decelerate
      further aging-related motor decline. In Brown-Norway/Fischer 344 F1 hybrid (BNF)
      rats, locomotor activity begins to decrease in middle age (12-18 months). One
      mechanism of aging-related motor decline may be decreased expression of GDNF
      family receptor, GFRalpha-1, which is decreased in substantia nigra (SN) between
      12 and 30 months old. Moderate exercise, beginning at 18 months old, increases
      nigral GFRalpha-1 and tyrosine hydroxylase (TH) expression within 2 months. In
      aged rats, replenishing aging-related loss of GFRalpha-1 in SN increases TH in SN
      alone and locomotor activity. A moderate exercise regimen was initiated in
      sedentary male BNF rats in a longitudinal study to evaluate if exercise could
      attenuate aging-related motor decline when initiated at two different ages in the
      latter half of the lifespan (18 or 24 months old). Motor decline was reversed in
      the 18-, but not 24-month-old, cohort. However, exercise efficacy in the 18-month
      old group was reduced as the rats reached 27 months old. GFRalpha-1 expression
      was not increased in either cohort. These studies suggest exercise can decelerate
      motor decline when begun in the latter half of the lifespan, but its efficacy may
      be limited by age of initiation. Decreased plasticity of GFRalpha-1 expression
      following exercise may limit its efficacy to reverse motor decline.

PMID- 29176897
TI  - Long-term prognostic impact of left ventricular remodeling after a first
      myocardial infarction in modern clinical practice.
AB  - BACKGROUND: The association of left ventricular remodeling (LVR) after myocardial
      infarction (MI) with the subsequent risk of heart failure (HF) and death has not
      been studied in patients receiving optimal secondary prevention. METHODS AND
      RESULTS: We performed a long-term clinical follow-up of patients included in 2
      prospective multicentric studies on LVR after first anterior MI. At 1-year
      echocardiography, LVR (>=20% increase in end-diastolic volume from baseline to 1
      year) occurred in 67/215 (31%) patients in cohort 1 and in 87/226 (38%) patients
      in cohort 2. The prescription rate of secondary prevention medications was very
      high (beta-blockers at 1 year: 90% and 95% for cohorts 1 and 2, respectively;
      angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACE
      I/ARB) at 1 year: 93% and 97% for cohorts 1 and 2, respectively). Median clinical
      follow-up after LVR assessment was 11.0 years in cohort 1 and 7.8 years in cohort
      2. In both cohorts, LVR patients had a progressive increase in the risk of
      cardiovascular death or hospitalization for HF (p = 0.0007 in cohort 1 and 0.009
      in cohort 2) with unadjusted hazard ratios of 2.52 [1.45-4.36] and 2.52 [1.23
      5.17], respectively. Similar results were obtained when cardiovascular death was
      considered as an isolated endpoint. After adjustement on baseline characteristics
      including ejection fraction, the association with the composite endpoint was
      unchanged. CONCLUSION: In a context of a modern therapeutic management with a
      large prescription of evidence-based medications, LVR remains independently
      associated with HF and cardiovascular death at long-term follow-up after MI.

PMID- 29176898
TI  - The influence of dietary and whole-body nutrient content on the excretion of a
      vertebrate consumer.
AB  - In many contexts, nutrient excretion by consumers can impact ecosystems by
      altering the availability of limiting nutrients. Variation in nutrient excretion
      can be predicted by mass balance models, most of which are premised on two key
      ideas: (1) consumers maintain fixed whole-body nutrient content (i.e., %N and
      %P), so-called fixed homeostasis; (2) if dietary nutrients are not matched to
      whole-body nutrients, excesses of any nutrient are released as excretion to
      maintain fixed homeostasis. Mass balance models thus predict that consumer
      excretion should be positively correlated with diet nutrients and negatively
      correlated with whole-body nutrients. Recent meta-analyses and field studies,
      however, have often failed to find these expected patterns, potentially because
      of a confounding influence-flexibility in whole-body nutrient content with diet
      quality (flexible homeostasis). Here, we explore the impact of flexible
      homeostasis on nutrient excretion by comparing the N and P excretion of four
      genetically diverged Trinidadian guppy (Poecilia reticulata) populations when
      reared on diets of variable P content. As predicted by mass balance, P excretion
      increased on the high-P diet, but, contrary to the notion of fixed homeostasis,
      guppy whole-body %P also increased on the high-P diet. While there was no overall
      correlation between excretion nutrients and whole-body nutrients, when the effect
      of diet on both whole-body and excretion nutrients was included, we detected the
      expected negative correlation between whole-body N:P and excretion N:P. This last
      result suggests that mass balance can predict excretion rates within species, but
      only if dietary effects on whole-body nutrient content are controlled. Flexible
      homeostasis can obscure patterns predicted by mass balance, creating an
      imperative to accurately capture an organism's diet quality in predicting its
      excretion rate.

PMID- 29176899
TI  - Supine posture changes lung volumes and increases ventilation heterogeneity in
      cystic fibrosis.
AB  - INTRODUCTION: Lung Clearance Index (LCI) is recognised as an early marker of
      cystic fibrosis (CF) lung disease. The effect of posture on LCI however is
      important when considering longitudinal measurements from infancy and when
      comparing LCI to imaging studies. METHODS: 35 children with CF and 28 healthy
      controls (HC) were assessed. Multiple breath washout (MBW) was performed both
      sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung
      volumes. These values were also corrected for the Fowler dead-space to create
      'alveolar' indices. RESULTS: From sitting to supine there was a significant
      increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01).
      LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude
      of change with posture for both LCIalv and FRCalv in both groups, with a greater
      effect of change in lung volume in HC compared with children with CF. The %
      change in LCIalv for all subjects correlated significantly with lung volume %
      changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r
      = 0.54,p<0.001)). CONCLUSION: There is a significant increase in LCI from sitting
      to supine, which we believe to be in part due to changes in lung volume and also
      increasing ventilation heterogeneity related to posture. This may have
      implications in longitudinal measurements from infancy to older childhood and for
      studies comparing supine imaging methods to LCI.

PMID- 29176900
TI  - Consensual punishment does not promote cooperation in the six-person prisoner's
      dilemma game with noisy public monitoring.
AB  - We study the effects of different punishment institutions on cooperation in a six
      person prisoner's dilemma game in which actors observe others' cooperation with
      some noise (i.e. imperfect public monitoring). Previous research has shown that
      peer punishment can sustain cooperation, if a certain proportion of group members
      punish defectors at a cost to themselves. However, in the presence of noise, co
      operators will sometimes be mistaken for defectors and punished, and defectors
      will sometimes be mistaken for co-operators and escape punishment. Both types of
      mistakes are detrimental for cooperation because cooperation is discouraged and
      defection is encouraged. By means of a laboratory experiment, we study whether
      this adverse effect of noise can be mitigated by consensual punishment. The more
      other group members have to agree on punishing a defector, the less likely will a
      co-operator be punished by mistake. We compare a punishment institution in which
      each subject decides individually whether to punish another, with institutions in
      which punishments are only implemented if subjects reach sufficient consensus
      that a particular group member should be punished. In conditions without noise,
      we find that cooperation and subjects' payoffs are higher if more consensus is
      required before a punishment is implemented. In conditions with noise,
      cooperation is lower if more consensus is required. Moreover, with noise,
      subjects' payoffs are lower under all punishment institutions than in the control
      condition without punishment opportunities. Our results narrow down the
      conditions under which punishment institutions can promote cooperation if such
      cooperation is noisy.

PMID- 29176902
TI  - Detection of Leishmania spp in silvatic mammals and isolation of Leishmania
      (Viannia) braziliensis from Rattus rattus in an endemic area for leishmaniasis in
      Minas Gerais State, Brazil.
AB  - Knowledge of potential reservoirs of Leishmania spp. in an anthropic environment
      is important so that surveillance and control measures can be implemented. The
      aim of this study was to investigate the infection by Leishmania in small mammals
      in an area located in Minas Gerais, Brazil, that undergoes changes in its natural
      environment and presents autochthonous human cases of cutaneous leishmaniasis
      (CL) and visceral leishmaniasis (VL). For the capture of the animals, Sherman and
      Tomahawk traps were used and distributed in the peridomicile of houses with
      reports of autochthonous cases of CL or VL. Six catches were carried out on two
      consecutive nights with intervals of two months during one year and samples of
      spleen, liver, tail skin, ear skin and bone marrow of the animals were obtained.
      Parasitological and molecular methods were used to detect the infection.
      Identification of the Leishmania species was performed by PCR RFLPhsp70. Twenty
      five animals of four species were captured: ten Rattus rattus, nine Didelphis
      albiventris, five Cerradomys subflavus and one Marmosops incanus. In the PCR
      hsp70, five animals were positive (20%). The Leishmania species identified in PCR
      RFLPhsp70 were: Leishmania braziliensis in D. albiventris (2), C. subflavus (1)
      and R. rattus (1) and Leishmania infantum in R. rattus (1). The highest
      positivity rate for L. braziliensis was obtained in the liver samples. The spleen
      was the only tissue positive for L. infantum. It was isolated in culture medium
      L. braziliensis from two samples (liver and spleen) of R. rattus. This is the
      first record of isolation of L. braziliensis from R. rattus in the southeastern
      region of Brazil. These results are relevant to the knowledge of the epidemiology
      of leishmaniasis in the region, mainly in the investigation of the presence of
      hosts and possible reservoirs of the parasite.

PMID- 29176901
TI  - Graded expression of source memory revealed by analysis of gaze direction.
AB  - During source memory studies, knowledge of some detail about the context of a
      previously experienced item or event is tested. Here, participants attended to
      different objects presented at different quadrants on a screen. In a later test
      phase, a single object was presented in all four quadrants, and participants
      verbally reported whether the object was new or previously seen (item
      recognition), and if it was previously seen, they indicated the original screen
      location (source memory). We combined this test with eye-tracking to determine
      whether attention to an object during encoding would correlate with later
      recognition of the object and memory of its source location, and whether eye
      movements at test can reveal attention to the correct source location in the
      absence of correct explicit verbal responses. The amount of time spent looking at
      an object during encoding was not related to later object recognition or source
      recollection. However, we found that eye movements at test reveal retention of
      source information about an object in the absence of accurate retrieval of source
      information as assessed by verbal response. When participants correctly
      recognized an object but incorrectly indicated the source information,
      significantly more time was spent looking at the correct source location than to
      incorrect, non-selected locations. Moreover, when participants correctly
      recognized an object but said they could not remember the source information,
      significantly more time was spent looking at the correct source location. These
      results are consistent with the hypothesis that eye movements are sensitive to
      attention or other graded mental processes which can underlie the retrieval of
      source memories that can then be expressed verbally in a thresholded manner.

PMID- 29176903
TI  - Axonal and myelinic pathology in 5xFAD Alzheimer's mouse spinal cord.
AB  - As an extension of the brain, the spinal cord has unique properties which could
      allow us to gain a better understanding of CNS pathology. The brain and cord
      share the same cellular components, yet the latter is simpler in cytoarchitecture
      and connectivity. In Alzheimer's research, virtually all focus is on brain
      pathology, however it has been shown that transgenic Alzheimer's mouse models
      accumulate beta amyloid plaques in spinal cord, suggesting that the cord
      possesses the same molecular machinery and conditions for plaque formation. Here
      we report a spatial-temporal map of plaque load in 5xFAD mouse spinal cord. We
      found that plaques started to appear at 11 weeks, then exhibited a time dependent
      increase and differential distribution along the cord. More plaques were found in
      cervical than other spinal levels at all time points examined. Despite heavy
      plaque load at 6 months, the number of cervical motor neurons in 5xFAD mice is
      comparable to wild type littermates. On detailed microscopic examination, fine
      beta amyloid-containing and beta sheet-rich thread-like structures were found in
      the peri-axonal space of many axons. Importantly, these novel structures appear
      before any plaque deposits are visible in young mice spinal cord and they co
      localize with axonal swellings at later stages, suggesting that these thread-like
      structures might represent the initial stages of plaque formation, and could play
      a role in axonal damage. Additionally, we were able to demonstrate increasing
      myelinopathy in aged 5xFAD mouse spinal cord using the lipid probe Nile Red with
      high resolution. Collectively, we found significant amyloid pathology in grey and
      white matter of the 5xFAD mouse spinal cord which indicates that this structure
      maybe a useful platform to study mechanisms of Alzheimer's pathology and disease
      progression.

PMID- 29176904
TI  - Mobile microscopy as a screening tool for oral cancer in India: A pilot study.
AB  - Oral cancer is the most common type of cancer among men in India and other
      countries in South Asia. Late diagnosis contributes significantly to this
      mortality, highlighting the need for effective and specific point-of-care
      diagnostic tools. The same regions with high prevalence of oral cancer have seen
      extensive growth in mobile phone infrastructure, which enables widespread access
      to telemedicine services. In this work, we describe the evaluation of an
      automated tablet-based mobile microscope as an adjunct for telemedicine-based
      oral cancer screening in India. Brush biopsy, a minimally invasive sampling
      technique was combined with a simplified staining protocol and a tablet-based
      mobile microscope to facilitate local collection of digital images and remote
      evaluation of the images by clinicians. The tablet-based mobile microscope
      (CellScope device) combines an iPad Mini with collection optics, LED illumination
      and Bluetooth-controlled motors to scan a slide specimen and capture high
      resolution images of stained brush biopsy samples. Researchers at the Mazumdar
      Shaw Medical Foundation (MSMF) in Bangalore, India used the instrument to collect
      and send randomly selected images of each slide for telepathology review.
      Evaluation of the concordance between gold standard histology, conventional
      microscopy cytology, and remote pathologist review of the images was performed as
      part of a pilot study of mobile microscopy as a screening tool for oral cancer.
      Results indicated that the instrument successfully collected images of sufficient
      quality to enable remote diagnoses that show concordance with existing
      techniques. Further studies will evaluate the effectiveness of oral cancer
      screening with mobile microscopy by minimally trained technicians in low-resource
      settings.

PMID- 29176906
TI  - Nonmarital First Births, Marriage, and Income Inequality.
AB  - Many aggregate-level studies suggest a relationship between economic inequality
      and socio-demographic outcomes such as family formation, health, and mortality;
      but individual-level evidence is lacking. Nor is there satisfactory evidence on
      the mechanisms by which inequality may have an effect. We study the determinants
      of transitions to a nonmarital first birth as a single parent or as a cohabiting
      parent compared to transitions to marriage prior to a first birth among
      unmarried, childless young adults in the National Longitudinal Survey of Youth,
      1997 cohort, from 1997 to 2011. We include measures of county-group-level
      household income inequality and of the availability of jobs typically held by
      high-school graduates and which pay above-poverty wages. We find that greater
      income inequality is associated with a reduced likelihood of transitioning to
      marriage prior to a first birth for both women and men. The association between
      levels of inequality and transitions to marriage can be partially accounted for
      by the availability of jobs of the type we measured. Some models also suggest
      that greater income inequality is associated with a reduced likelihood of
      transitioning to a first birth while cohabiting.

PMID- 29176905
TI  - Oral versus intravenous methylprednisolone for the treatment of multiple
      sclerosis relapses: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Intravenous glucocorticoids are recommended for multiple sclerosis
      (MS). However, they can be inconvenient and expensive. Due to their convenience
      and low cost, oral glucocorticoids may be an alternative treatment. Recently,
      several studies have shown that there is no difference in efficacy and safety
      between oral methylprednisolone (oMP) and intravenous methylprednisolone (ivMP).
      OBJECTIVES: We sought to assess the clinical efficacy, safety and tolerability of
      oral methylprednisolone versus intravenous methylprednisolone for MS relapses in
      this meta-analysis. METHODS: Randomized controlled trials (RCTs) evaluating the
      clinical efficacy, safety and tolerability of oral methylprednisolone versus
      intravenous methylprednisolone for MS relapses were searched in PubMed, Cochrane
      Library, Medline, EMBASE and China Biology Medicine until October 25, 2016,
      without language restrictions. The proportion of patients who had improved by day
      28 was chosen as the efficacy outcome. We chose the risk ratio (RR) to analyze
      each trial with the 95% confidence interval (95% CI). We also used the fixed
      effects model (Mantel-Haenszel approach) to calculate the pooled relative effect
      estimates. RESULTS: A total of 5 trials were identified, which included 369
      patients. The results of our meta-analysis revealed that no significant
      difference existed in relapse improvement at day 28 between oMP and ivMP (RR
      0.96, 95% CI 0.84 to 1.10). No evidence of heterogeneity existed among the trials
      (P = 0.45, I2 = 0%). Both treatments were equally safe and well tolerated except
      that insomnia was more likely to occur in the oMP group compared to the ivMP
      group. CONCLUSION: Our meta-analysis reveals strong evidence that oMP is not
      inferior to ivMP in increasing the proportion of patients experiencing clinical
      improvement at day 28. In addition, both routes of administration are equally
      well tolerated and safe. These findings suggest that we may be able to replace
      ivMP with oMP to treat MS relapses.

PMID- 29176907
TI  - Correction: Assessing the global reach and value of a provider-facing healthcare
      app using large-scale analytics.
AB  - [This corrects the article DOI: 10.1136/bmjgh-2017-000299.].

PMID- 29176908
TI  - Modified Facile Synthesis for Quantitatively Fluorescent Carbon Dots.
AB  - A simple yet consequential modification was made to the popular carbonization
      processing of citric acid - polyethylenimine precursor mixtures to produce carbon
      dots (CDots). The modification was primarily on pushing the carbonization
      processing a little harder at a higher temperature, such as the hydrothermal
      processing condition of around 330  degrees C for 6 hours. The CDots thus
      produced are comparable in spectroscopic and other properties to those obtained
      in other more controlled syntheses including the deliberate chemical
      functionalization of preprocessed and selected small carbon nanoparticles,
      demonstrating the consistency in CDots and reaffirming their general definition
      as carbon nanoparticles with surface passivation by organic or other species.
      Equally significant is the finding that the modified processing of citric acid -
      polyethylenimine precursor mixtures could yield CDots of record-setting
      fluorescence performance, approaching the upper limit of being quantitatively
      fluorescent. Thus, the reported work serves as a demonstration on not only the
      need in selecting the right processing conditions and its associated
      opportunities in one-pot syntheses of CDots, but also the feasibility in pursuing
      the preparation of quantitatively fluorescent CDots, which represents an
      important milestone in the development and understanding of these fluorescent
      carbon nanomaterials.

PMID- 29176909
TI  - Computer-aided Molecular Design of Water Compatible Visible Light
      Photosensitizers for Dental Adhesive.
AB  - Dental adhesive resin undergoes phase separation during its infiltration through
      the wet demineralized dentin and it has been observed previously that the
      hydrophilic-rich phase is a vulnerable region for failure due to the lack of
      photo-polymerization and crosslinking density. The lack of photo-polymerization
      is mostly due to the partitioning of photo-initiators in low concentrations
      within this phase. Here, a computational approach has been employed to design
      candidate water compatible visible light photosensitizers which could improve the
      photo-polymerization of the hydrophilic-rich phase. This study is an extension of
      our previous work. QSPRs were developed for properties related to the photo
      polymerization reaction of the adhesive monomers and hydrophilicity of the
      photosensitizer using connectivity indices as descriptors. QSPRs and structural
      constraints were formulated into an optimization problem which was solved
      stochastically via Tabu Search. Four candidate photosensitizer molecules have
      been proposed here which have the iminium ion as a common feature.

PMID- 29176910
TI  - The effect of Ca2+ ions and ionic strength on Mn(II) oxidation by spores of the
      marine Bacillus sp. SG-1.
AB  - Manganese(IV) oxides, believed to form primarily through microbial activities,
      are extremely important mineral phases in marine environments where they scavenge
      a variety of trace elements and thereby control their distributions. The presence
      of various ions common in seawater are known to influence Mn oxide mineralogy yet
      little is known about the effect of these ions on the kinetics of bacterial
      Mn(II) oxidation and Mn oxide formation. We examined factors affecting bacterial
      Mn(II) oxidation by spores of the marine Bacillus sp. strain SG-1 in natural and
      artificial seawater of varying ionic conditions. Ca2+ concentration dramatically
      affected Mn(II) oxidation, while Mg2+, Sr2+, K+, Na+ and NO3- ions had no effect.
      The rate of Mn(II) oxidation at 10mM Ca2+ (seawater composition) was four or five
      times that without Ca2+. The relationship between Ca2+ content and oxidation rate
      demonstrates that the equilibrium constant is small (on the order of 0.1) and the
      binding coefficient is 0.5. The pH optimum for Mn(II) oxidation changed depending
      on the amount of Ca2+ present, suggesting that Ca2+ exerts a direct effect on the
      enzyme perhaps as a stabilizing bridge between polypeptide components. We also
      examined the effect of varying concentrations of NaCl or KNO3 (0 mM - 2000 mM) on
      the kinetics of Mn(II) oxidation in solutions containing 10 mM Ca2+. Mn(II)
      oxidation was unaffected by changes in ionic strength (I) below 0.2, but it was
      inhibited by increasing salt concentrations above this value. Our results suggest
      that the critical coagulation concentration is around 200 mM of salt (I = ca.
      0.2), and that the ionic strength of seawater (I > 0.2) accelerates the
      precipitation of Mn oxides around the spores. Under these conditions, the
      aggregation of Mn oxides reduces the supply of dissolved O2 and/or Mn2+ and
      inhibits the Mn(II) -> Mn(III) step controlling the enzymatic oxidation of
      Mn(II). Our results suggest that the hardness and ionic strength of the aquatic
      environment at circumneutral pH strongly influences the rate of biologically
      mediated Mn(II) oxidation.

PMID- 29176911
TI  - Episodes of fluvial and volcanic activity in Mangala Valles, Mars.
AB  - A new mapping-based study of the 900-km-long Mangala Valles outflow system was
      motivated by the availability of new high-resolution images and continued debates
      about the roles of water and lava in outflow channels on Mars. This study uses
      photogeologic analysis, geomorphic surface mapping, cratering statistics, and
      relative stratigraphy. Results show that Mangala Valles underwent at least two
      episodes of fluvial activity and at least three episodes of volcanic activity
      during the Late Amazonian. The occurrence of scoured bedrock at the base of the
      mapped stratigraphy, in addition to evidence provided by crater retention ages,
      suggests that fluvial activity preceded the deposition of two of the volcanic
      units. Crater counts performed at 30 locations throughout the area have allowed
      us to construct the following timeline: (1) formation of Noachian Highlands and
      possible initial flooding event(s) before ~1 Ga, (2) emplacement of Tharsis lava
      flows in the valley from ~700 to 1000 Ma, (3) a megaflooding event at ~700-800 Ma
      sourced from Mangala Fossa, (4) valley fill by a sequence of lava flows sourced
      from Mangala Fossa ~400-500 Ma, (5) another megaflooding event from ~400 Ma, (6)
      a final phase of volcanism sourced from Mangala Fossa ~300-350 Ma, and (7)
      emplacement of eolian sedimentary deposits in the northern portion of the valley
      ~300 Ma. These results are consistent with alternating episodes of aqueous
      flooding and volcanism in the valles. This pattern of geologic activity is
      similar to that of other outflow systems, such as Kasei Valles, suggesting that
      there is a recurring, and perhaps coupled, nature of these processes on Mars.

PMID- 29176912
TI  - Older Adults' Perceptions of Nutrition as Protective Against Detrimental Effects
      of Environmental Pollution.
AB  - The aging process makes older adults vulnerable to the detrimental health effects
      of environmental contaminants. Our study assessed older adults' perceptions
      regarding diet being protective against environmental contaminants, their levels
      of concern about exposure, and their interest in learning about protective food
      related strategies. A needs assessment to collect such information has not been
      conducted among older adults. Health fair survey results showed that they
      perceived diet as beneficial against contaminants, were concerned about health
      implications of exposure, and were interested in learning how to protect health
      through diet-related strategies. Results suggest that a nutrition-focused
      curriculum addressing how dietary strategies can help protect against
      environmental contaminants is needed for Extension professionals.

PMID- 29176914
TI  - Efficient route to pre-organized and linear polyaminopolycarboxylates: Cy-TTHA,
      Cy-DTPA and mono/di- reactive, tert-butyl protected TTHA/Cy-TTHA.
AB  - Pre-organized polyaminopolycarboxylate chelators Cy-TTHA and Cy-DTPA were
      synthesized via modular five-step syntheses from commercially available starting
      materials in ~ 62% and 47% overall yields, respectively. Furthermore, strategies
      are reported for the efficient preparation of mono- and di-reactive, tert-butyl
      protected TTHA/Cy-TTHA to selectively functionalize central chelators' carboxylic
      acids.

PMID- 29176915
TI  - The Association of Ethnic Pride With Health and Social Outcomes Among Young Black
      and Latino Men After Release From Jail.
AB  - The goal of this study was to understand whether ethnic pride among young,
      incarcerated Black and Latino men was associated with successful community
      reentry. We interviewed 397 Black and Latino men 16 to 18 years old in a New York
      City jail and then again 1 year after their release to determine the relationship
      between participants' sense of ethnic pride during incarceration, and substance
      use, violence, recidivism, and education/ employment after release from jail.
      Participants with higher ethnic pride scores were less likely to engage in
      illegal activities and be reincarcerated. Ethnic pride was also associated with
      feeling safe in gangs and positive attitudes toward avoiding violence in
      situations of conflict. Ethnic pride was not associated with substance use,
      education, or engagement in community-based organizations post release. This
      study demonstrated that ethnic pride might be a source of strength that young men
      of color can harness for successful community reentry after release from jail.

PMID- 29176913
TI  - Addiction Treatment Clients' Reactions to Graphic Warning Labels on Cigarette
      Packs.
AB  - Graphic warning labels (GWLs) on cigarette packs have been tested among diverse
      groups at high risk for tobacco use. However, little is known about the
      effectiveness of GWL interventions for persons with substance use disorders,
      whose smoking prevalence is 3 to 4 times that of the general population. After an
      experimental study which exposed clients in residential addiction treatment to
      GWLs for 30 days, we conducted five focus groups with trial participants (N = 33)
      to explore how exposure to the labels may have impacted their readiness to quit
      smoking. Focus group interviews were analyzed thematically. Interviewees reported
      that GWLs were more effective than text-based warnings for increasing quit
      intentions due to greater cognitive and emotional impact. Male and female
      interviewees expressed gender-specific reactions to the labels. Addiction
      treatment programs are a strategic site for GWL and other tobacco interventions
      due to the tobacco-vulnerable populations they serve.

PMID- 29176916
TI  - Simulation and Measurement of Through-the-Earth, Extremely Low-Frequency Signals
      Using Copper-Clad Steel Ground Rods.
AB  - The underground mining environment can greatly affect radio signal propagation.
      Understanding how the earth affects signal propagation is a key to evaluating
      communications systems used during a mine emergency. One type of communication
      system is through-the-earth, which can utilize extremely low frequencies (ELF).
      This paper presents the simulation and measurement results of recent National
      Institute for Occupational Safety and Health (NIOSH) research aimed at
      investigating current injection at ELF, and in particular, ground contact
      impedance. Measurements were taken at an outside surface testing location. The
      results obtained from modeling and measurement are characterized by electrode
      impedance, and the voltage received between two distant electrodes. This paper
      concludes with a discussion of design considerations found to affect low
      frequency communication systems utilizing ground rods to inject a current into
      the earth.

PMID- 29176917
TI  - Fluvial geomorphology on Earth-like planetary surfaces: A review.
AB  - Morphological evidence for ancient channelized flows (fluvial and fluvial-like
      landforms) exists on the surfaces of all of the inner planets and on some of the
      satellites of the Solar System. In some cases, the relevant fluid flows are
      related to a planetary evolution that involves the global cycling of a volatile
      component (water for Earth and Mars; methane for Saturn's moon Titan). In other
      cases, as on Mercury, Venus, Earth's moon, and Jupiter's moon Io, the flows were
      of highly fluid lava. The discovery, in 1972, of what are now known to be fluvial
      channels and valleys on Mars sparked a major controversy over the role of water
      in shaping the surface of that planet. The recognition of the fluvial character
      of these features has opened unresolved fundamental questions about the
      geological history of water on Mars, including the presence of an ancient ocean
      and the operation of a hydrological cycle during the earliest phases of planetary
      history. Other fundamental questions posed by fluvial and fluvial-like features
      on planetary bodies include the possible erosive action of large-scale
      outpourings of very fluid lavas, such as those that may have produced the
      remarkable canali forms on Venus; the ability of exotic fluids, such as methane,
      to create fluvial-like landforms, as observed on Saturn's moon, Titan; and the
      nature of sedimentation and erosion under different conditions of planetary
      surface gravity. Planetary fluvial geomorphology also illustrates fundamental
      epistemological and methodological issues, including the role of analogy in
      geomorphological/geological inquiry.

PMID- 29176918
TI  - The influence of transcranial alternating current stimulation (tACS) on fluid
      intelligence: An fMRI study.
AB  - The past decades have witnessed a huge interest in uncovering the neural bases of
      intelligence (e.g., Stelmack, & Houlihan, 1995; Stelmack, Knott, & Beauchamp,
      2003). This study investigated the influence of transcranial alternating current
      stimulation (tACS) on fluid intelligence performance and corresponding brain
      activation. Previous findings showed that left parietal theta tACS leads to a
      transient increase in fluid reasoning performance. In an attempt to extend and
      replicate these findings, we combined theta tACS with fMRI. In a double-blind
      sham-controlled experiment, N = 20 participants worked on two intelligence tasks
      (matrices and paper folding) after theta tACS was applied to the left parietal
      cortex. Stimulation-induced brain activation changes were recorded during task
      processing using fMRI. Results showed that theta tACS significantly increased
      fluid intelligence performance when working on difficult items in the matrices
      test; no effect was observed for the visuo-spatial paper folding test. Whole
      brain analyses showed that left parietal brain stimulation was accompanied by
      lower activation in task-irrelevant brain areas. Complemental ROI analyses
      revealed a tendency towards lower activation in the left inferior parietal
      cortex. These findings corroborate the functional role of left parietal theta
      activity in fluid reasoning and are in line with the neural efficiency
      hypothesis.

PMID- 29176920
TI  - The role of extra-foveal processing in 3D imaging.
AB  - The field of medical image quality has relied on the assumption that metrics of
      image quality for simple visual detection tasks are a reliable proxy for the more
      clinically realistic visual search tasks. Rank order of signal detectability
      across conditions often generalizes from detection to search tasks. Here, we
      argue that search in 3D images represents a paradigm shift in medical imaging:
      radiologists typically cannot exhaustively scrutinize all regions of interest
      with the high acuity fovea requiring detection of signals with extra-foveal areas
      (visual periphery) of the human retina. We hypothesize that extra-foveal
      processing can alter the detectability of certain types of signals in medical
      images with important implications for search in 3D medical images. We compare
      visual search of two different types of signals in 2D vs. 3D images. We show that
      a small microcalcification-like signal is more highly detectable than a larger
      mass-like signal in 2D search, but its detectability largely decreases (relative
      to the larger signal) in the 3D search task. Utilizing measurements of observer
      detectability as a function retinal eccentricity and observer eye fixations we
      can predict the pattern of results in the 2D and 3D search studies. Our findings:
      1) suggest that observer performance findings with 2D search might not always
      generalize to 3D search; 2) motivate the development of a new family of model
      observers that take into account the inhomogeneous visual processing across the
      retina (foveated model observers).

PMID- 29176919
TI  - Clinically differentiating life-course-persistent and adolescence-limited conduct
      problems: Is age-of-onset really enough?
AB  - One important subtyping of behavior problems is Moffitt's (1993) "life-course
      persistent" (LCP) and "adolescent limited" (AL) categories of antisocial
      behavior, which she differentiated in terms of high impulsivity, poor academic
      performance, and aggression. These problems may be exacerbated by the cumulative
      effects of chronic stress. Copious evidence has documented validity and
      developmental differences between these subtypes, whereas far fewer data exist
      regarding their clinical utility, in spite of the Diagnostic and Statistical
      Manual's nomenclature including corresponding subtypes based on age-of-onset of
      behavioral symptoms. The present study evaluated how well age-of-onset based
      subtyping identifies distinct developmental patterns of antisocial behavior
      corresponding to Moffitt's subtypes in terms of risk factors and gender between
      LCP and AL in a prospective sample of chronically stressed youth. A computerized
      assessment tool (ALEXSA(c)) was used to obtain data from 1,147 youth aged 8-16.
      Implications for clinical assessment and intervention strategy, particularly with
      stressed youth, are discussed.

PMID- 29176921
TI  - Foveated Model Observers to predict human performance in 3D images.
AB  - We evaluate 3D search requires model observers that take into account the
      peripheral human visual processing (foveated models) to predict human observer
      performance. We show that two different 3D tasks, free search and location-known
      detection, influence the relative human visual detectability of two signals of
      different sizes in synthetic backgrounds mimicking the noise found in 3D digital
      breast tomosynthesis. One of the signals resembled a microcalcification (a small
      and bright sphere), while the other one was designed to look like a mass (a
      larger Gaussian blob). We evaluated current standard models observers (Hotelling;
      Channelized Hotelling; non-prewhitening matched filter with eye filter, NPWE; and
      non-prewhitening matched filter model, NPW) and showed that they incorrectly
      predict the relative detectability of the two signals in 3D search. We propose a
      new model observer (3D Foveated Channelized Hotelling Observer) that incorporates
      the properties of the visual system over a large visual field (fovea and
      periphery). We show that the foveated model observer can accurately predict the
      rank order of detectability of the signals in 3D images for each task. Together,
      these results motivate the use of a new generation of foveated model observers
      for predicting image quality for search tasks in 3D imaging modalities such as
      digital breast tomosynthesis or computed tomography.

PMID- 29176923
TI  - Effects Of Symmetry On The Structural Controllability Of Neural Networks: A
      Perspective.
AB  - The controllability of a dynamical system or network describes whether a given
      set of control inputs can completely exert influence in order to drive the system
      towards a desired state. Structural controllability develops the canonical
      coupling structures in a network that lead to un-controllability, but does not
      account for the effects of explicit symmetries contained in a network. Recent
      work has made use of this framework to determine the minimum number and location
      of the optimal actuators necessary to completely control complex networks. In
      systems or networks with structural symmetries, group representation theory
      provides the mechanisms for how the symmetry contained in a network will
      influence its controllability, and thus affects the placement of these critical
      actuators, which is a topic of broad interest in science from ecological,
      biological and man-made networks to engineering systems and design.

PMID- 29176922
TI  - Peptide-coated semiconductor nanocrystals for biomedical applications.
AB  - We have developed a new functionalization approach for semiconductor nanocrystals
      based on a single-step exchange of surface ligands with custom-designed peptides.
      This peptide-coating technique yield small, monodisperse and very stable water
      soluble NCs that remain bright and photostable. We have used this approach on
      several types of core and core-shell NCs in the visible and near-infrared
      spectrum range and used fluorescence correlation spectroscopy for rapid
      assessment of the colloidal and photophysical properties of the resulting
      particles. This peptide coating strategy has several advantages: it yields probes
      that are immediately biocompatible; it is amenable to improvements of the
      different properties (solubilization, functionalization, etc) via rational
      design, parallel synthesis, or molecular evolution; it permits the combination of
      several functions on individual NCs. These functionalized NCs have been used for
      diverse biomedical applications. Two are discussed here: single-particle tracking
      of membrane receptor in live cells and combined fluorescence and PET imaging of
      targeted delivery in live animals.

PMID- 29176924
TI  - Novel phonotactic learning: Tracking syllable-position and co-occurrence
      constraints.
AB  - Are syllable-level and co-occurrence representations simultaneously available
      when one learns novel phonotactics? After training on word-medial consonant
      restrictions (e.g., word-medial onsets P/Z, codas D/F, and cross-syllable
      consonant clusters FP/DZ in items like baF.Pev, tiD.Zek), adults falsely
      recognized novel items containing restricted consonants with the same co
      occurrences (e.g., FP) more often than those with different co-occurrences (e.g.,
      FZ) when syllable-position information was kept constant (e.g., vuF.Pet vs.
      vuF.Zet; Experiment 1). Thus, adults tracked co-occurrence information.
      Additionally, even when co-occurrence information was different from training,
      participants more often falsely recognized novel items that contained restricted
      consonants in the same (e.g., onset-Z) rather than different syllable positions
      (e.g., coda-Z), whether the restricted consonants were in the same (word-medial,
      e.g., vuF.Zet vs. vuZ.Fet, Experiment 2) or different word positions (word-edge,
      e.g., Zut.veF vs. Fut.veZ, Experiment 3). Thus, adults also tracked syllable
      level information. These findings show that adults spontaneously represent sound
      sequences at multiple levels.

PMID- 29176925
TI  - Two HTS options for a 600 MHz insert of a 1.3 GHz LTS/HTS NMR magnet: YBCO and
      BSCCO.
AB  - In 2008, the Phase 3 program to complete a 1.3 GHz (30.5 T) NMR magnet started at
      the Francis Bitter Magnet Laboratory, Massachusetts Institute of Technology. It
      comprises two sub-phases, 3A and 3B. In Phase 3A, a 600 MHz high temperature
      superconductor (HTS) insert magnet (H600) will be designed, constructed, and
      operated in the bore of a 500 MHz low temperature superconductor (LTS) background
      magnet. This will be followed by Phase 3B, in which the H600 will be combined
      with a 700 MHz LTS background magnet to complete a 1.3 GHz NMR LTS/HTS magnet.
      This paper presents and discusses design issues for two conductor options for
      H600: BiSCCO-2223 (Bi2223) and coated-YBCO or its variants, here designated as
      YBCO. For each conductor option, we focused on the following issues: 1) elastic
      and thermal properties; 2) critical current vs. field performance; 3) splice and
      index heat dissipations; 4) mechanical and thermal stresses; and 5) protection.

PMID- 29176926
TI  - Changes in the genetic structure of an invasive earthworm species (Lumbricus
      terrestris, Lumbricidae) along an urban - rural gradient in North America.
AB  - European earthworms were introduced to North America by European settlers about
      400 years ago. Human-mediated introductions significantly contributed to the
      spread of European species, which commonly are used as fishing bait and are often
      disposed deliberately in the wild. We investigated the genetic structure of
      Lumbricus terrestris in a 100 km range south of Calgary, Canada, an area that
      likely was devoid of this species two decades ago. Genetic relationships among
      populations, gene flow, and migration events among populations were investigated
      using seven microsatellite markers and the mitochondrial 16S rDNA gene.
      Earthworms were collected at different distances from the city and included
      fishing baits from three different bait distributors. The results suggest that
      field populations in Alberta established rather recently and that bait and field
      individuals in the study area have a common origin. Genetic variance within
      populations decreased outside of the urban area, and the most distant populations
      likely originated from a single introduction event. The results emphasise the
      utility of molecular tools to understand the spatial extent and connectivity of
      populations of exotic species, in particular soil-delling species, that invade
      native ecosystems and to obtain information on the origin of populations. Such
      information is crucial for developing management and prevention strategies to
      limit and control establishment of non-native earthworms in North America.

PMID- 29176928
TI  - The Management of Disclosure in Children's Accounts of Domestic Violence:
      Practices of Telling and Not Telling.
AB  - Children and young people who experience domestic violence are often represented
      as passive witnesses, too vulnerable to tell the stories of their own lives. This
      article reports on findings from a 2 year European research project
      (Understanding Agency and Resistance Strategies, UNARS) with children and young
      people in Greece, Italy, Spain and the UK, who had experienced domestic violence.
      It explores children and young people's understandings of their own capacity to
      reflect on and disclose their experiences Extracts from individual interviews
      with 107 children and young people (age 8-18) were analysed. Three themes are
      presented, that illustrate children and young people's strategies for managing
      disclosure: (1) "Being silenced or choosing silence?", explores children and
      young people's practices of self-silencing; (2) "Managing disclosures: Finding
      ways to tell" outlines how children and young people value self-expression, and
      the strategies they use to disclose safely; and in (3) "Speaking with many
      voices" considers how children and young people's accounts of their experiences
      are constituted relationally, and are often polyvocal. The article concludes that
      children and young people can be articulate, strategic and reflexive
      communicators, and that good support for families struggling with domestic
      violence must enable space for children and young people's voice to be heard.
      This is possible only in an integrated framework able to encompass multiple
      layers and perspectives, rather than privileging the adult point of view.
      Practitioners who work with families affected by domestic violence need to
      recognize that children and young people are able to reflect on and speak about
      their experiences. This requires that attention is paid to the complexity of
      children and young people's communication practices, and the relational context
      of those communications.

PMID- 29176930
TI  - Growth kinetics of omega particles in beta-Ti matrix studied by in-situ small
      angle x-ray scattering.
AB  - Nucleation and growth kinetics of nanoparticles of hexagonal omega phase in a
      body-centered cubic beta titanium matrix in single crystals of beta-Ti alloys
      were investigated by small-angle x-ray scattering measured in-situ during ageing
      at various temperatures up to 450  degrees C. The experimental data were compared
      with numerical simulations based on a three-dimensional short-range order model
      of nanoparticle self-ordering. The x-ray contrast of the particles is caused by
      an inhomogeneous distribution of impurity atoms (Mo, Fe and Al), whose density
      profile around growing nanoparticles was simulated by solving the corresponding
      diffusion equation with moving boundary conditions. From the analysis of the
      experimental data we determined the mean distance and size of the nanoparticles
      and confirmed the validity of the ? t1/3 growth law following from the Lifshitz
      Slyozov-Wagner theory. From a detailed comparison of the experimental data with
      simulations we also assessed the diffusion coefficient of the impurity atoms and
      its activation energy.

PMID- 29176929
TI  - Family Drawings before and after Treatment for Child Conduct Problems: Fluidity
      of Family Dysfunction.
AB  - Children's drawings have previously been found to reflect their representations
      of family relationships. The present study examined whether evidence-based parent
      training for child conduct problems impacts on representations of family
      functioning using the Family Drawing Paradigm (FDP). N = 53 clinic-referred
      children (aged 3-15) with conduct problems and their families were assessed pre
      treatment and at 6-month follow-up on a modified version of the FDP. Analyses of
      changes in the FDP revealed improvements in family functioning but not tone of
      language (as indicated by written descriptors) following treatment. Higher family
      dysfunction scores were associated with increased levels of callous-unemotional
      (CU) traits in the children pre-treatment. Children with high levels of CU,
      however, demonstrated greater change in FDP dysfunction than a low CU group,
      resulting in similar levels at follow-up. CU traits also moderated the
      association between change in family warmth and conduct problem severity, with
      increased FDP warmth more strongly related to improved conduct problems in the
      high vs. the low CU group. FDP drawings are sensitive to changes in family
      functioning arising from parent training, accounting for unique variance in child
      outcomes independent of verbal reports.

PMID- 29176927
TI  - Conceptualizing Eukaryotic Metabolic Sensing and Signaling.
AB  - For almost all cells, nutrient availability, from glucose to amino acids,
      dictates their growth or developmental programs. This nutrient availability is
      closely coupled to the overall intracellular metabolic state of the cell.
      Therefore, cells have evolved diverse, robust and versatile modules to sense
      intracellular metabolic states, activate signaling outputs and regulate outcomes
      to these states. Yet, signaling and metabolism have been viewed as important but
      separate. This short review attempts to position aspects of intracellular
      signaling from a metabolic perspective, highlighting how conserved, core
      principles of metabolic sensing and signaling can emerge from an understanding of
      metabolic regulation. I briefly explain the nature of metabolic sensors, using
      the example of the AMP activated protein kinase (AMPK) as an "energy sensing"
      hub. Subsequently, I explore how specific central metabolites, particularly
      acetyl-CoA, but also S -adenosyl methionine and SAICAR, can act as signaling
      molecules. I extensively illustrate the nature of a metabolic signaling hub using
      the specific example of the Target of Rapamycin Complex 1 (TORC1), and amino acid
      sensing. A highlight is the emergence of the lysosome/vacuole as a metabolic and
      signaling hub. Finally, the need to expand our understanding of the intracellular
      dynamics (in concentration and localization) of several metabolites, and their
      signaling hubs is emphasized.

PMID- 29176931
TI  - On the Use of Summary Comorbidity Measures for Prognosis and Survival Treatment
      Effect Estimation.
AB  - Prognostic scores have been proposed as outcome based confounder adjustment
      scores akin to propensity scores. However, prognostic scores have not been widely
      used in the substantive literature. Instead, comorbidity scores, which are
      limited versions of prognostic scores, have been used extensively by clinical and
      health services researchers. A comorbidity is an existing disease an individual
      has in addition to a primary condition of interest, such as cancer. Comorbidity
      scores are used to reduce the dimension of a vector of comorbidity variables into
      a single scalar variable. Such scores are often added to regression models with
      other non-comorbidity variables such as age and sex, both for analyzing prognosis
      and for confounder adjustment when analyzing treatment effects. Despite their
      widespread use, the properties of and conditions under which comorbidity scores
      are valid dimension reduction tools in statistical models is largely unknown. In
      this article, we show that under relatively standard assumptions, comorbidity
      scores can have equal prognostic and confounder-adjustment abilities as the
      individual comorbidity variables, but that biases can occur if there are
      additional effects, such as interactions, of covariates beyond that captured by
      the comorbidity score. Simulations were performed to illustrate empirical
      properties and a data example using breast cancer data from the SEER Medicare
      Database demonstrates the application of these results.

PMID- 29176932
TI  - Advanced nurse practitioners in municipal healthcare as a way to meet the growing
      healthcare needs of the frail elderly: a qualitative interview study with
      managers, doctors and specialist nurses.
AB  - Background: The number of frail elderly people with complex nursing and medical
      care needs is increasing, and consequently, the healthcare burden. The
      implementation of Advanced Nurse Practitioners globally has been shown to make
      healthcare more effective and increase patient safety, continuity of care and
      access to care. In Sweden, research about Advanced Nurse Practitioners is
      limited. Thus, this study aimed to investigate the opinions of managers, doctors
      and nurses in primary care and municipal healthcare about the role of ANPs in
      municipal healthcare as a way to meet the increasing healthcare needs of the
      frail elderly. Methods: Managers, doctors and specialist nurses in primary care
      and municipal healthcare adopted a qualitative, descriptive design through 12
      semi-structured interviews. The data were analysed using content analysis.
      Results: The participants expressed both opportunities as well as challenges with
      Advanced Nurse Practitioners in municipal healthcare. This role considered to
      satisfy frail elderly people's healthcare needs and making the healthcare more
      effective as the doctors would have more time for other patients. The challenges
      mainly consist of doubts from the managers whether the nurses would be motivated
      to pursue further education to become an Advanced Nurse Practitioner if the role
      becomes a reality. The doctors were unsure if the nurses would consider taking
      the responsibility the role would imply. Conclusions: Advanced Nurse Practitioner
      is considered to be a valuable resource not only for the frail elderly but also
      for the nurses in the municipal healthcare and for the doctors in primary care as
      they probably would make healthcare more effective. They might be a way to meet
      the increasing healthcare needs of frail elderly, however there are also
      challenges to overcome before they can become a reality in a Swedish healthcare
      context. Consequently, this role deserves further investigation.

PMID- 29176933
TI  - A clinical pathway for the management of difficult venous access.
AB  - Background: Many patients are admitted to hospital with non-visible or palpable
      veins, often resulting in multiple painful attempts at cannulation, anxiety and
      catheter failure. We developed a difficult intravenous pathway at our institution
      to reduce the burden of difficult access for patients by increasing first attempt
      success with ultrasound guidance. The emphasis was to provide a solution for
      hospitalised patients after business hours by training the after-hours clinical
      support team in ultrasound guided cannulation. Methods: Inception cohort study of
      patients referred to the after-hours clinical support team including outcomes
      such as number of attempts at cannulation before and after referral, insertion
      site, type of device inserted and recorded pain score for attempts prior to
      referral and for attempts by the after-hours clinical support team. Results:
      Between January and December 2016, 379 patients were referred to the after-hours
      clinical support team for placement of a peripheral intravenous catheter under
      ultrasound guidance. The median number of unsuccessful attempts before referral
      was 2 (IQR 2, 4), this ranged between 1 attempt to 10 attempts compared to only 1
      attempt (IQR 1, 1, p < 0.001) with no more than 2 attempts in total by the after
      hours clinical support team. The first time success rate by the after-hours
      clinical support team was 93% (n = 348). The median pain score for attempts with
      ultrasound use was 2/10 (IQR 1-3) compared to 7/10 (IQR 5-9) for previous
      attempts without ultrasound (p < 0.001). Conclusion: The use of ultrasound
      guidance for peripheral intravenous catheter insertion by the after-hours
      clinical support team for patients with difficult venous access has been
      successful at our institution with 9 out of every 10 catheters inserted at first
      attempt with significantly lower recorded pain scores.

PMID- 29176934
TI  - Nurses' competencies in home healthcare: an interview study.
AB  - Background: Nurses working in Home healthcare (HHC) are facing major challenges
      since more advanced care and treatment are increasingly being carried out in
      patients' homes. The aim of this study has been to explore how nurses experience
      their competencies in HHC situations. Methods: This study has a qualitative and
      explorative design. Ten nurses were interviewed and data was analyzed using
      content analysis. Results: The themes "Being a capable nurse", "Being a useful
      nurse" and "Being a subordinate and dependent nurse" were identified. Nurses want
      to be capable of taking care of patients, to develop their competencies and to
      perform their duties in the way required. They also want their work to be useful
      and to provide good and safe HHC. Finally, nurses want to improve HHC care by
      applying their competencies. Simultaneously, they are subordinate and dependent
      in relation to their manager and also dependent upon their manager's interest in
      encouraging nurses' competence development. Conclusions: Nurses in HHC are
      responsible for many seriously ill patients and they want to contribute to good
      and safe patient care. To maintain patient safety, reduce the risk for burnout
      and staff turnover as well as to contribute to a sustainable development of the
      work, strategies for transferring competencies between nurses and efforts for
      competence development are needed.

PMID- 29176935
TI  - Restoration of miR-29b exerts anti-cancer effects on glioblastoma.
AB  - Background: Glioblastoma multiforme (GBM) is known as one of the most fatal forms
      of cancer. MicroRNAs have been widely implicated in the regulation of mammalian
      development and pathogenesis. The brain-enriched miR-29 subfamilies are known to
      be exclusively expressed in the developing brain, and they are aberrantly down
      regulated in GBM. This study aims to elucidate the role of miR-29b in GBM
      development and the feasibility of therapeutic targeting using conjugated
      nanoparticles. Methods: After confirmation of miR-29b expression levels in GBM
      tissues by analysis of open source data, the anticancer effect of miR-29b was
      tested by the introduction of syn-hsa-miR-29b-3p in the A172 GBM cell line. In
      vitro studies of cell viability and apoptosis and ex vivo study using GBM tissue
      slice cultures from 3 patients and nanoparticle delivery of miR-29b were
      performed. Results: We discovered an increase in apoptotic cell populations with
      the introduction of miR-29b in the GBM cell line. An established human-derived
      GBM tissue slice culture system confirmed the anticancer effect of miR-29b
      conjugated nanoparticles. Using PCR array, we found that exogenous miR-29b
      inhibits the expression of COL1A2, COL3A1, COL4A1, ELN, ITGA11, MMP24, and SPARC,
      which mediates an anticancer effect. Conclusions: miR-29b may serve as a putative
      therapeutic molecule when its expression is restored using a nanoparticle
      delivery system in GBM.

PMID- 29176936
TI  - Role of microRNA-33a in regulating the expression of PD-1 in lung adenocarcinoma.
AB  - Background: MiRNAs are vital in functioning as either oncogenes or tumor
      suppressors in the cell cycle. Target transcripts for immune checkpoint molecules
      such as PD-1/PD-L1 and (programmed cell death-1/its ligand and cytotoxic T
      lymphocyte antigen 4) have proven to be beneficial against several solid tumors,
      including lung adenocarcinoma. Methods: Simultaneous quantification of the
      expression level of miR-33a and PD-1, PD-L1 and CTLA4 mRNAs with NanoString
      technology was performed in 88 lung adenocarcinoma specimens. A cohort of 323
      lung adenocarcinoma patients from the cancer genome atlas (TCGA) database was
      further analyzed, in order to test our hypothesis. Potential interference of PD
      1, PD-L1 and CTLA4 gene expression by miR-33a was predicted using the microRNA
      target prediction program RNA22. Results: High miR-33a expression was
      significantly associated with younger (p = 0.005), female (p = 0.04), patients
      with low grade (p < 0.0001), early stage (p = 0.03) tumors, and better survival.
      The hypothesis of the involvement of miR-33a in PD-1/PD-L1/CTLA4 mechanisms was
      corroborated by the finding of putative miR-33a binding sites in all three genes
      using the RNA22 method. We found an inverse correlation between miR-33a and PD-1
      levels (p = 0.01), as well as for PD-L1 (p = 0.01) and CTLA4 (p = 0.03)
      expression, and a significant better prognosis for patients with high miR-33a/low
      PD-1. TCGA database analysis confirmed that miR-33a high levels were associated
      with low PD-1 expression and with longer survival on a larger population.
      Conclusions: Our study emphasizes the notion of a potential value of miR-33a as a
      favorable prognostic marker through PD-1 regulation.

PMID- 29176938
TI  - A proteomic approach to understanding the pathogenesis of idiopathic macular hole
      formation.
AB  - Idiopathic macular holes (IMH) are full-thickness defects of retinal tissue that
      cause severe vision loss due to disruption of the anatomic fovea. Abnormal
      vitreous traction is involved in the formation of macular holes. Both glial cells
      and hyalocytes contribute to epiretinal membrane formation in IMH. In order to
      gain further insight into the pathophysiology of IMH, we conducted a discovery
      phase investigation of the vitreous proteome in four patients with macular holes
      and six controls using one-dimensional gel fractionation and liquid
      chromatography-tandem mass spectrometry analyses on an Orbitrap Elite mass
      spectrometer. Of a total of 5912 vitreous proteins, 32 proteins had increased and
      39 proteins had decreased expression in IMH compared with controls, using a false
      discovery rate approach with p value < 0.001 and q value < 0.05. IMH was
      associated with increased expression of proteins in the complement pathway, alpha
      2-macroglobulin, a major inducer of Muller glial cell migration, fibrinogen, and
      extracellular matrix proteins, and decreased expression of proteins involved in
      protein folding and actin filament binding. A proteomic approach revealed
      proteins and biological pathways that may be involved in the pathogenesis of IMH
      and could be targeted for future studies.

PMID- 29176937
TI  - Proteomic profiling identifies markers for inflammation-related tumor-fibroblast
      interaction.
AB  - Background: Cancer associated fibroblasts are activated in the tumor
      microenvironment and contribute to tumor progression, angiogenesis, extracellular
      matrix remodeling, and inflammation. Methods: To identify proteins characteristic
      for fibroblasts in colorectal cancer we used liquid chromatography-tandem mass
      spectrometry to derive protein abundance from whole-tissue homogenates of human
      colorectal cancer/normal mucosa pairs. Alterations of protein levels were
      determined by two-sided t test with greater than threefold difference and an FDR
      of < 0.05. Public available datasets were used to predict proteins of stromal
      origin and link protein with mRNA regulation. Immunohistochemistry confirmed the
      localization of selected proteins. Results: We identified a set of 24 proteins
      associated with inflammation, matrix organization, TGFbeta receptor signaling and
      angiogenesis mainly originating from the stroma. Most prominent were increased
      abundance of SerpinB5 in the parenchyme and latent transforming growth factor
      beta-binding protein, thrombospondin-B2, and secreted protein acidic-and-cysteine
      rich in the stroma. Extracellular matrix remodeling involved collagens type VIII,
      XII, XIV, and VI as well as lysyl-oxidase-2. In silico analysis of mRNA levels
      demonstrated altered expression in the tumor and the adjacent normal tissue as
      compared to mucosa of healthy individuals indicating that inflammatory activation
      affected the surrounding tissue. Immunohistochemistry of 26 tumor specimen
      confirmed upregulation of SerpinB5, thrombospondin B2 and secreted protein acidic
      and-cysteine-rich. Conclusions: This study demonstrates the feasibility of
      detecting tumor- and compartment-specific protein-signatures that are
      functionally meaningful by proteomic profiling of whole-tissue extracts together
      with mining of RNA expression datasets. The results provide the basis for further
      exploration of inflammation-related stromal markers in larger patient cohorts and
      experimental models.

PMID- 29176939
TI  - Views of Experienced Electronic Cigarette Users.
AB  - Background: Awareness and use of electronic cigarettes (e-cigs) has increased
      significantly in the last five years, but little is known about the experiences,
      satisfaction, opinions and preferences of e-cigs users. Method: 1177 participants
      completed an online survey about their electronic cigarette preferences, of which
      200 were randomly selected for analysis. The data was analyzed using both
      qualitative and quantitative methods. Results: Participants found the design, the
      ability to customize, and the quality of vapor to be the most important
      characteristics of the device. Participants thought the most positive aspects of
      e-cig use were help to quit smoking, improved overall health, and reduced cost.
      The negative aspects associated with use were mainly related to side effects,
      such as dry mouth. When asked to explain how e-cigs were used differently than
      cigarettes, participants reported puffing more regularly, but taking fewer puffs
      per session. Conclusions: Experienced e-cig users stated that initiating e-cig
      use helped them to quit or reduce their conventional smoking, which they believe
      reduced their health risks. In comparison to cigarette smoking, e-cig users
      reported using their e-cig more times per day, but with fewer puffs at each use
      time. Users acknowledged that more research is needed to understand the safety
      and long-term effects of use. They mentioned dry mouth as a common side effect
      and common problems with reliability of e-cigs. Understanding these views may
      help health professionals to assess and assist e-cig users, and in the future,
      may help regulators to improve quality and reduce risks.

PMID- 29176940
TI  - Ultrafast Near-Infrared Light-triggered Intracellular Uncaging to Probe Cell
      Signaling.
AB  - The possibility of regulating cell signaling with high spatial and temporal
      resolution within individual cells and complex cellular networks has important
      implications in biomedicine. In this report, we demonstrate a general strategy
      that uses near-infrared tissue-penetrating laser pulses to uncage biomolecules
      from plasmonic gold-coated liposomes, i.e. plasmonic liposomes, to activate cell
      signaling in a non-thermal, ultrafast and highly controllable fashion. Near
      infrared picosecond laser pulse induces transient nanobubbles around plasmonic
      liposomes. The mechanical force generated from the collapse of nanobubbles
      rapidly ejects encapsulated compound within 0.1 ms. We showed that single pulse
      irradiation triggers the rapid intracellular uncaging of calcein from plasmonic
      liposomes inside endo-lysosomes. The uncaged calcein then evenly distributes over
      the entire cytosol and nucleus. Furthermore, we demonstrated the ability to
      trigger calcium signaling in both an immortalized cell line and primary dorsal
      root ganglion (DRG) neurons by intracellular uncaging of inositol triphosphate
      (IP3), an endogenous cell calcium signaling second messenger. Compared with other
      uncaging techniques, this ultrafast near-infrared light-driven molecular uncaging
      method is easily adaptable to deliver a wide range of bioactive molecules with an
      ultrafast optical switch, enabling new possibilities to investigate signaling
      pathways within individual cells and cellular networks.

PMID- 29176941
TI  - Perceptual Decisions in the Presence of Relevant and Irrelevant Sensory Evidence.
AB  - Perceptual decisions in the presence of decision-irrelevant sensory information
      require a selection of decision-relevant sensory evidence. To characterize the
      mechanism that is responsible for separating decision-relevant from irrelevant
      sensory information we asked human subjects to make judgments about one of two
      simultaneously present motion components in a random dot stimulus. Subjects were
      able to ignore the decision-irrelevant component to a large degree, but their
      decisions were still influenced by the irrelevant sensory information.
      Computational modeling revealed that this influence was not simply the
      consequence of subjects forgetting at times which stimulus component they had
      been instructed to base their decision on. Instead, residual irrelevant
      information always seems to be leaking through, and the decision process is
      captured by a net sensory evidence signal being accumulated to a decision
      threshold. This net sensory evidence is a linear combination of decision-relevant
      and irrelevant sensory information. The selection process is therefore well
      described by a strong linear gain modulation, which, in our experiment, resulted
      in the relevant sensory evidence having at least 10 times more impact on the
      decision than the irrelevant evidence.

PMID- 29176942
TI  - Cognitive Decline in Neuronal Aging and Alzheimer's Disease: Role of NMDA
      Receptors and Associated Proteins.
AB  - Molecular changes associated with neuronal aging lead to a decrease in cognitive
      capacity. Here we discuss these alterations at the level of brain regions, brain
      cells, and brain membrane and cytoskeletal proteins with an special focus in NMDA
      molecular changes through aging and its effect in cognitive decline and Alzheimer
      disease. Here, we propose that some neurodegenerative disorders, like Alzheimer's
      disease (AD), are characterized by an increase and acceleration of some of these
      changes.

PMID- 29176943
TI  - Deployment of Mobile EEG Technology in an Art Museum Setting: Evaluation of
      Signal Quality and Usability.
AB  - Electroencephalography (EEG) has emerged as a powerful tool for quantitatively
      studying the brain that enables natural and mobile experiments. Recent advances
      in EEG have allowed for the use of dry electrodes that do not require a
      conductive medium between the recording electrode and the scalp. The overall goal
      of this research was to gain an understanding of the overall usability and signal
      quality of dry EEG headsets compared to traditional gel-based systems in an
      unconstrained environment. EEG was used to collect Mobile Brain-body Imaging
      (MoBI) data from 432 people as they experienced an art exhibit in a public
      museum. The subjects were instrumented with either one of four dry electrode EEG
      systems or a conventional gel electrode EEG system. Each of the systems was
      evaluated based on the signal quality and usability in a real-world setting.
      First, we describe the various artifacts that were characteristic of each of the
      systems. Second, we report on each system's usability and their limitations in a
      mobile setting. Third, to evaluate signal quality for task discrimination and
      characterization, we employed a data driven clustering approach on the data from
      134 of the 432 subjects (those with reliable location tracking information and
      usable EEG data) to evaluate the power spectral density (PSD) content of the EEG
      recordings. The experiment consisted of a baseline condition in which the
      subjects sat quietly facing a white wall for 1 min. Subsequently, the
      participants were encouraged to explore the exhibit for as long as they wished
      (piece-viewing). No constraints were placed upon the individual in relation to
      action, time, or navigation of the exhibit. In this freely-behaving approach, the
      EEG systems varied in their capacity to record characteristic modulations in the
      EEG data, with the gel-based system more clearly capturing stereotypical alpha
      and beta-band modulations.

PMID- 29176944
TI  - Elucidating Sensorimotor Control Principles with Myoelectric Musculoskeletal
      Models.
AB  - There is an old saying that you must walk a mile in someone's shoes to truly
      understand them. This mini-review will synthesize and discuss recent research
      that attempts to make humans "walk a mile" in an artificial musculoskeletal
      system to gain insight into the principles governing human movement control. In
      this approach, electromyography (EMG) is used to sample human motor commands;
      these commands serve as inputs to mathematical models of muscular dynamics, which
      in turn act on a model of skeletal dynamics to produce a simulated motor action
      in real-time (i.e., the model's state is updated fast enough produce smooth
      motion without noticeable transitions; Manal et al., 2002). In this mini-review,
      these are termed myoelectric musculoskeletal models (MMMs). After a brief
      overview of typical MMM design and operation principles, the review will
      highlight how MMMs have been used for understanding human sensorimotor control
      and learning by evoking apparent alterations in a user's biomechanics, neural
      control, and sensory feedback experiences.

PMID- 29176945
TI  - Sound-Evoked Biceps Myogenic Potentials Reflect Asymmetric Vestibular Drive to
      Spastic Muscles in Chronic Hemiparetic Stroke Survivors.
AB  - Aberrant vestibular nuclear function is proposed to be a principle driver of limb
      muscle spasticity after stroke. We sought to determine whether altered cortical
      modulation of descending vestibulospinal pathways post-stroke could impact the
      excitability of biceps brachii motoneurons. Twelve chronic hemispheric stroke
      survivors aged 46-68 years were enrolled. Sound evoked biceps myogenic potentials
      (SEBMPs) were recorded from the spastic and contralateral biceps muscles using
      surface EMG electrodes. We assessed the impact of descending vestibulospinal
      pathways on biceps muscle activity and evaluated the relationship between
      vestibular function and the severity of spasticity. Spastic SEBMP responses were
      recorded in 11/12 subjects. Almost 60% of stroke subjects showed evoked responses
      solely on the spastic side. These data strongly support the idea that vestibular
      drive is asymmetrically distributed to biceps motoneuron pools in hemiparetic
      spastic stroke survivors. This abnormal vestibular drive is very likely to be a
      factor mediating the striking differences in motoneuron excitability between the
      clinically affected and clinically spared sides. This study extends our previous
      observations on vestibular nuclear changes following hemispheric stroke and
      potentially sheds light on the underlying mechanisms of post-stroke spasticity.

PMID- 29176946
TI  - Individual Differences in Verbal and Spatial Stroop Tasks: Interactive Role of
      Handedness and Domain.
AB  - A longstanding debate in psychology concerns the relation between handedness and
      cognitive functioning. The present study aimed to contribute to this debate by
      comparing performance of right- and non-right-handers on verbal and spatial
      Stroop tasks. Previous studies have shown that non-right-handers have better
      inter-hemispheric interaction and greater access to right hemisphere processes.
      On this ground, we expected performance of right- and non-right-handers to differ
      on verbal and spatial Stroop tasks. Specifically, relative to right-handers, non
      right-handers should have greater Stroop effect in the color-word Stroop task,
      for which inter-hemispheric interaction does not seem to be advantageous to
      performance. By contrast, non-right-handers should be better able to overcome
      interference in the spatial Stroop task. This is for their preferential access to
      the right hemisphere dealing with spatial material and their greater inter
      hemispheric interaction with the left hemisphere hosting Stroop task processes.
      Our results confirmed these predictions, showing that handedness and the
      underlying brain asymmetries may be a useful variable to partly explain
      individual differences in executive functions.

PMID- 29176947
TI  - Cortical Contribution to Linear, Non-linear and Frequency Components of Motor
      Variability Control during Standing.
AB  - Motor variability is an inherent feature of all human movements and reflects the
      quality of functional task performance. Depending on the requirements of the
      motor task, the human sensory-motor system is thought to be able to flexibly
      govern the appropriate level of variability. However, it remains unclear which
      neurophysiological structures are responsible for the control of motor
      variability. In this study, we tested the contribution of cortical cognitive
      resources on the control of motor variability (in this case postural sway) using
      a dual-task paradigm and furthermore observed potential changes in control
      strategy by evaluating Ia-afferent integration (H-reflex). Twenty healthy
      subjects were instructed to stand relaxed on a force plate with eyes open and
      closed, as well as while trying to minimize sway magnitude and performing a
      "subtracting-sevens" cognitive task. In total 25 linear and non-linear parameters
      were used to evaluate postural sway, which were combined using a Principal
      Components procedure. Neurophysiological response of Ia-afferent reflex loop was
      quantified using the Hoffman reflex. In order to assess the contribution of the H
      reflex on the sway outcome in the different standing conditions multiple mixed
      model ANCOVAs were performed. The results suggest that subjects were unable to
      further minimize their sway, despite actively focusing to do so. The dual-task
      had a destabilizing effect on PS, which could partly (by 4%) be counter-balanced
      by increasing reliance on Ia-afferent information. The effect of the dual-task
      was larger than the protective mechanism of increasing Ia-afferent information.
      We, therefore, conclude that cortical structures, as compared to peripheral
      reflex loops, play a dominant role in the control of motor variability.

PMID- 29176948
TI  - The Oncogenic Role of Tribbles 1 in Hepatocellular Carcinoma Is Mediated by a
      Feedback Loop Involving microRNA-23a and p53.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy associated with a high risk
      of recurrence and metastasis and a poor prognosis. Here, we examined the
      involvement of the pseudokinase Tribbles 1 (TRIB1), a scaffold protein associated
      with several malignancies, in HCC and investigated the underlying mechanisms.
      TRIB1 was upregulated in HCC tissues and cell lines in correlation with low
      levels of p53. TRIB1 gain and loss of function experiments indicated that TRIB1
      promoted HCC cell viability concomitant with the downregulation of p53, and
      induced HCC cell migration, invasion, and epithelial-mesenchymal transition.
      TRIB1 was identified as a target of microRNA-23a (miR-23a), and miR-23a
      overexpression downregulated TRIB1 and upregulated p53 in HCC cells. Ectopic
      expression of TRIB1 upregulated beta-catenin and its effectors c-myc and MMP-7 in
      a p53-dependent manner. TRIB1 silencing inhibited tumor growth and promoted
      apoptosis in vivo via a mechanism that would involve the modulation of p53 and
      beta-catenin signaling. The present results indicate that TRIB1 promotes HCC
      tumorigenesis and invasiveness via a feedback loop that involves the modulation
      of its expression by miR-23a with the likely downregulation of p53, and suggest
      the involvement of the beta-catenin signaling pathway. These findings suggest
      potential targets for the treatment of HCC and therefore merit further
      investigation.

PMID- 29176949
TI  - Commentary: Coordinated infraslow neural and cardiac oscillations mark fragility
      and offline periods in mammalian sleep.

PMID- 29176950
TI  - Cardiovascular and Cutaneous Responses to the Combination of Alcohol and Soft
      Drinks: The Way to Orthostatic Intolerance?
AB  - Aim: Acute ingestion of alcohol is often accompanied by cardiovascular
      dysregulation, malaise and even syncope. The full hemodynamic and cutaneous
      responses to the combination of alcohol and sugar (i.e., alcopops), a common
      combination in young people, and the mechanisms for the propensity to orthostatic
      intolerance are not well established. Thus, the purpose of this study was to
      evaluate the cardiovascular and cutaneous responses to alcopops in young
      subjects. Methods: Cardiovascular and cutaneous responses were assessed in 24
      healthy young subjects (12 men, 12 women) sitting comfortably and during
      prolonged active standing with a 30-min baseline and 130 min following ingestion
      of 400 mL of either: water, water + 48 g sugar, water + vodka (1.28 mL.kg-1 of
      body weight, providing 0.4 g alcohol.kg-1), water + sugar + vodka, according to a
      randomized cross-over design. Results: Compared to alcohol alone, vodka + sugar
      induced a lower breath alcohol concentration (BrAC), blood pressure and total
      peripheral resistance (p < 0.05), a higher cardiac output and heart rate (p <
      0.05) both in sitting position and during active standing. In sitting position
      vodka + sugar consumption also led to a greater increase in skin blood flow and
      hand temperature (p < 0.05) and a decrease in baroreflex sensitivity (p < 0.05).
      We observed similar results between men and women both in sitting position and
      during active standing. Conclusion: Despite lower BrAC, ingestion of alcopops
      induced acute vasodilation and hypotension in sitting position and an encroach of
      the hemodynamic reserve during active standing. Even if subjects did not feel any
      signs of syncope these results could be of clinical importance with higher doses
      of alcohol or if combined to other hypotensive challenges.

PMID- 29176952
TI  - Modulation of Neurogenesis through the Promotion of Energy Production Activity Is
      behind the Antidepressant-Like Effect of Colonial Green Alga, Botryococcus
      braunii.
AB  - Algae have been recognized as important resources providing functional components
      due to their capacity to exert beneficial effects on health. Therefore, there is
      increasing interest in investigating the biological activity of algae. In this
      study, we evaluated the antidepressant-like effect of the administration of 100
      mg/kg/day of the ethanol extract of colonial green alga Botryococcus braunii
      (EEB) for 14 consecutive days in the forced swimming test (FST)-induced
      depression in imprinting control region (ICR) mice. Imipramine, a commercial
      antidepressant drug, was used as a positive control. In addition, we investigated
      the molecular mechanisms underlying the effect of EEB by measuring ATP production
      and by assessing any change in gene expression at the end of the treatment using
      real-time polymerase chain reaction (PCR) and microarray assays. We showed that
      the immobility time in the water-administered control (FST stress) group
      gradually increased from day 1 to day 14. However, treatment with EEB caused a
      significant decrease of immobility time in the FST compared with that in the FST
      stress group. Microarray and real-time PCR results revealed that EEB treatment
      induced variation in the expression of several genes associated with
      neurogenesis, energy metabolism, and dopamine synthesis. Interestingly, we
      revealed that only EEB treatment enhanced the promotion of energy production,
      while treatment with imipramine was ineffective. Our study provides the first
      evidence that B. braunii enhances energy production, which may contribute to the
      modulation of neurogenesis and to the enhancement of dopaminergic function, in
      turn potentially underlying the antistress- and antidepressant-like effects that
      we observed.

PMID- 29176951
TI  - Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain.
AB  - Since the discovery of ouabain as a cardiotonic steroid hormone present in higher
      mammals, research about it has progressed rapidly and several of its
      physiological and pharmacological effects have been described. Ouabain can behave
      as a stress hormone and adrenal cortex is its main source. Direct effects of
      ouabain are originated due to the binding to its receptor, the Na+/K+-ATPase, on
      target cells. This interaction can promote Na+ transport blockade or even
      activation of signaling transduction pathways (e.g., EGFR/Src-Ras-ERK pathway
      activation), independent of ion transport. Besides the well-known effect of
      ouabain on the cardiovascular system and blood pressure control, compelling
      evidence indicates that ouabain regulates a number of immune functions.
      Inflammation is a tightly coordinated immunological function that is also
      affected by ouabain. Indeed, this hormone can modulate many inflammatory events
      such as cell migration, vascular permeability, and cytokine production. Moreover,
      ouabain also interferes on neuroinflammation. However, it is not clear how
      ouabain controls these events. In this brief review, we summarize the updates of
      ouabain effect on several aspects of peripheral and central inflammation,
      bringing new insights into ouabain functions on the immune system.

PMID- 29176953
TI  - Mitochondrial Proton Leak Compensates for Reduced Oxidative Power during Frequent
      Hypothermic Events in a Protoendothermic Mammal, Echinops telfairi.
AB  - The lesser hedgehog tenrec (Echinops telfairi) displays reptile-like
      thermoregulatory behavior with markedly high variability in body temperature and
      metabolic rate. To understand how energy metabolism copes with this flexibility,
      we studied the bioenergetics of isolated liver mitochondria from cold (20 degrees
      C) and warm (27 degrees C) acclimated tenrecs. Different acclimation temperatures
      had no impact on mitochondrial respiration using succinate as the substrate.
      Mimicking the variation of body temperature by changing assay temperatures from
      22 to 32 degrees C highlighted temperature-sensitivity of respiration. The 40%
      reduction of respiratory control ratio (RCR) at 22 degrees C compared to 32
      degrees C, a common estimate for mitochondrial efficiency, was caused by reduced
      substrate oxidation capacity. The simultaneous measurement of mitochondrial
      membrane potential enabled the precise assessment of efficiency with corrected
      respiration rates. Using this method, we show that proton leak respiration at the
      highest common membrane potential was not affected by acclimation temperature but
      was markedly decreased by assay temperature. Using membrane potential corrected
      respiration values, we show that the fraction of ATP-linked respiration (coupling
      efficiency) was maintained (70-85%) at lower temperatures. Collectively, we
      demonstrate that compromised substrate oxidation was temperature-compensated by
      the reduction of proton leak, thus maintaining the efficiency of mitochondrial
      energy conversion. Therefore, membrane potential data suggest that adjustments of
      mitochondrial proton leak contribute to energy homeostasis during
      thermoregulatory flexibility of tenrecs.

PMID- 29176954
TI  - Response to: Commentary: Sex Differences in the Peripheral Immune System in
      Patients with Depression.

PMID- 29176955
TI  - Affording Sustainability: Adopting a Theory of Affordances as a Guiding Heuristic
      for Environmental Policy.
AB  - Human behavior is an underlying cause for many of the ecological crises faced in
      the 21st century, and there is no escaping from the fact that widespread behavior
      change is necessary for socio-ecological systems to take a sustainable turn.
      Whilst making people and communities behave sustainably is a fundamental
      objective for environmental policy, behavior change interventions and policies
      are often implemented from a very limited non-systemic perspective. Environmental
      policy-makers and psychologists alike often reduce cognition 'to the brain,'
      focusing only to a minor extent on how everyday environments systemically afford
      pro-environmental behavior. Symptomatic of this are the widely prevalent attitude
      action, value-action or knowledge-action gaps, understood in this paper as the
      gulfs lying between sustainable thinking and behavior due to lack of affordances.
      I suggest that by adopting a theory of affordances as a guiding heuristic,
      environmental policy-makers are better equipped to promote policies that
      translate sustainable thinking into sustainable behavior, often self
      reinforcingly, and have better conceptual tools to nudge our socio-ecological
      system toward a sustainable turn. Affordance theory, which studies the relations
      between abilities to perceive and act and environmental features, is shown to
      provide a systemic framework for analyzing environmental policies and the ecology
      of human behavior. This facilitates the location and activation of leverage
      points for systemic policy interventions, which can help socio-ecological systems
      to learn to adapt to more sustainable habits. Affordance theory is presented to
      be applicable and pertinent to technically all nested levels of socio-ecological
      systems from the studies of sustainable objects and households to sustainable
      urban environments, making it an immensely versatile conceptual policy tool.
      Finally, affordance theory is also discussed from a participatory perspective.
      Increasing the fit between local thinking and external behavior possibilities
      entails a deep understanding of tacit and explicit attitudes, values, knowledge
      as well as physical and social environments, best gained via inclusive and
      polycentric policy approaches.

PMID- 29176956
TI  - Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.
AB  - Objective: To perform a meta-analysis of randomized, blinded, multiple sclerosis
      (MS) clinical trials, to test the hypothesis that efficacy of immunomodulatory
      disease-modifying therapies (DMTs) on MS disability progression is strongly
      dependent on age. Methods: We performed a literature search with pre-defined
      criteria and extracted relevant features from 38 clinical trials that assessed
      efficacy of DMTs on disability progression. We fit a linear regression, weighted
      for trial sample size, and duration, to examine the hypothesis that age has a
      defining effect on the therapeutic efficacy of immunomodulatory DMTs. Results:
      More than 28,000 MS subjects participating in trials of 13 categories of
      immunomodulatory drugs are included in the meta-analysis. The efficacy of
      immunomodulatory DMTs on MS disability strongly decreased with advancing age (R2
      = 0.6757, p = 6.39e-09). Inclusion of baseline EDSS did not significantly improve
      the model. The regression predicts zero efficacy beyond approximately age 53
      years. The comparative efficacy rank derived from the regression residuals
      differentiates high- and low-efficacy drugs. High-efficacy drugs outperform low
      efficacy drugs in inhibiting MS disability only for patients younger than 40.5
      years. Conclusion: The meta-analysis supports the notion that progressive MS is
      simply a later stage of the MS disease process and that age is an essential
      modifier of a drug efficacy. Higher efficacy treatments exert their benefit over
      lower efficacy treatments only during early stages of MS, and, after age 53, the
      model suggests that there is no predicted benefit to receiving immunomodulatory
      DMTs for the average MS patient.

PMID- 29176957
TI  - Manual Dexterity and Intralimb Coordination Assessment to Distinguish Different
      Levels of Impairment in Boccia Players with Cerebral Palsy.
AB  - Background: Boccia is a paralympic sport played by athletes with severe
      neurological impairments affecting all four limbs. Impaired manual dexterity (MD)
      and intralimb coordination (ILC) may limit individuals' ability to perform
      certain activities such as grasping, releasing, or manipulating objects, which
      are essential tasks for daily life or to participate in para sports such as
      boccia. However, there are currently no specific instruments available to assess
      hand-arm coordination in boccia players with severe cerebral palsy (CP). Purpose:
      To design new sport-specific coordination tests to assess impaired MD and ILC in
      boccia players; afterward, quantify to what extent their coordination is impaired
      compared to a control group (CG) without neurological impairments. Methods:
      Seventy-three recreational boccia players with severe CP (BC1: age = 34.01 +/-
      16.43 years; BC2: age = 33.97 +/- 14.29 years), and 19 healthy adults (age =
      27.89 +/- 7.08 years) completed the test battery. The Box and Block test (BBT)
      and Box and Ball test (BBLT) were used to assess MD and four tapping tests to
      assess upper ILC. Results: Both MD tests were able to discriminate between sport
      classes. Boccia players obtained better scores in the BBLT in comparison to the
      BBT, showing that the BBLT had more appropriate testing features. On the other
      hand, only one of the ILC tests was able to discriminate between sport classes,
      displaying the highest practical significance (d = -1.12). Participants with CP
      scored significantly worse in all the coordination tests compared to the CG.
      Conclusion: Using sport-specific equipment facilitated grasp function during the
      MD assessment. Regarding the ILC, the type of movement (continuous vs. discrete)
      seems to be more relevant for classification than the movement direction
      (vertical vs. horizontal) or the presence of a ball.

PMID- 29176958
TI  - New Multiple Sclerosis Disease Severity Scale Predicts Future Accumulation of
      Disability.
AB  - The search for the genetic foundation of multiple sclerosis (MS) severity remains
      elusive. It is, in fact, controversial whether MS severity is a stable feature
      that predicts future disability progression. If MS severity is not stable, it is
      unlikely that genotype decisively determines disability progression. An
      alternative explanation tested here is that the apparent instability of MS
      severity is caused by inaccuracies of its current measurement. We applied
      statistical learning techniques to a 902 patient-years longitudinal cohort of MS
      patients, divided into training (n = 133) and validation (n = 68) sub-cohorts, to
      test four hypotheses: (1) there is intra-individual stability in the rate of
      accumulation of MS-related disability, which is also influenced by extrinsic
      factors. (2) Previous results from observational studies are negatively affected
      by the insensitive nature of the Expanded Disability Status Scale (EDSS). The
      EDSS-based MS Severity Score (MSSS) is further disadvantaged by the inability to
      reliably measure MS onset and, consequently, disease duration (DD). (3) Replacing
      EDSS with a sensitive scale, i.e., Combinatorial Weight-Adjusted Disability Score
      (CombiWISE), and substituting age for DD will significantly improve predictions
      of future accumulation of disability. (4) Adjusting measured disability for the
      efficacy of administered therapies and other relevant external features will
      further strengthen predictions of future MS course. The result is a MS disease
      severity scale (MS-DSS) derived by conceptual advancements of MSSS and a
      statistical learning method called gradient boosting machines (GBM). MS-DSS
      greatly outperforms MSSS and the recently developed Age Related MS Severity Score
      in predicting future disability progression. In an independent validation cohort,
      MS-DSS measured at the first clinic visit correlated significantly with
      subsequent therapy-adjusted progression slopes (r = 0.5448, p = 1.56e-06)
      measured by CombiWISE. To facilitate widespread use of MS-DSS, we developed a
      free, interactive web application that calculates all aspects of MS-DSS and its
      contributing scales from user-provided raw data. MS-DSS represents a much-needed
      tool for genotype-phenotype correlations, for identifying biological processes
      that underlie MS progression, and for aiding therapeutic decisions.

PMID- 29176959
TI  - Gender-Specific Relationship between Obesity and Major Depression.
AB  - Objective: Prior research suggests a bidirectional relationship between obesity
      and major depressive disorder (MDD), but the results have been heterogeneous.
      Differences between males and females in the association of MDD with obesity may
      contribute to inconsistent results. Thus, this study was designed to determine
      whether sex has a differential effect on the relationship between MDD and
      obesity, and to explore the potential mechanisms. Methods: All participants were
      diagnosed with MDD, and depression severity was measured using the 17-item
      Hamilton Depression Rating Scale. Body weight and height were measured to
      calculate body mass index (BMI). Body composition, including total fat, trunk
      fat, android fat, and visceral fat mass, was measured by dual-energy X-ray
      absorptiometry. Subjects provided blood samples, and serum was extracted for
      measuring the inflammatory factors using human immunoassay kits. Results: Among
      all obesity measures, depressed women had greater BMI and total body fat. By
      contrast, depressed men had greater visceral fat mass. However, only in depressed
      women was depression correlated with several measures of obesity, including BMI,
      total body fat, and visceral fat mass. A stepwise multiple regression analysis
      was conducted, and only visceral fat entered the regression model and was most
      predictive of depression in women (beta = 0.60, p = 0.007). Moreover, compared
      with depressed men, depressed women had higher leptin levels after controlling
      for BMI, total body fat, and visceral fat. Conclusion: These results highlight
      gender differences in determining the association between obesity and depression,
      and elevated leptin level is a potential mechanism linking MDD to obesity in
      depressed women. Understanding a gender-specific relationship between obesity and
      MDD would allow clinicians to target and personalize therapies in the hope of
      improving health outcomes.

PMID- 29176961
TI  - Clinical and Biochemical Associations with Diabetic Retinopathy in Male Patients
      in the Gaza Strip.
AB  - Background: There are limited data on the prevalence and risk factors for
      diabetic retinopathy (DR) in the Gaza Strip. Objective: To assesses clinical and
      biochemical associated with DR in males with type 2 diabetes mellitus (T2DM) in
      the Gaza Strip. Methods: One hundred and fifty males with T2DM from the Gaza
      Strip underwent a questionnaire interview, serum biochemical analysis, and
      assessment of their previous urine and blood results. Results: The prevalence of
      DR was 24.7%. The duration of diabetes and prevalence of neuropathy, nephropathy,
      cardiovascular disease, and recurrent infections were significantly higher among
      patients with DR compared with those without DR (p < 0.05). Serum urea,
      creatinine, glucose, cholesterol, and low-density lipoprotein cholesterol were
      significantly elevated, whilst eGFR and high-density lipoprotein cholesterol were
      significantly lower in patients with DR compared with patients without DR (p <
      0.05). Urinary albumin concentration and albumin creatinine ratio (ACR) was
      higher in patients with DR. ACR correlated significantly with the duration of
      T2DM (r = 0.311, p < 0.001), glucose (r = 0.479, p < 0.001), urea (r = 0.337, p <
      0.001), creatinine (r = 0.275, p = 0.001), and GFR (r = -0.275, p < 0.001).
      Conclusion: These data show a high prevalence of DR in an unselected cohort of
      patients with T2DM and relationships to modifiable risk factors in Gaza.

PMID- 29176963
TI  - The Patterns and Drivers of Bacterial and Fungal beta-Diversity in a Typical
      Dryland Ecosystem of Northwest China.
AB  - Dryland ecosystems cover more than 30% of the terrestrial area of China, while
      processes that shape the biogeographic patterns of bacterial and fungal beta
      diversity have rarely been evaluated synchronously. To compare the biogeographic
      patterns and its drivers of bacterial and fungal beta-diversity, we collected 62
      soil samples from a typical dryland region of northwest China. We assessed
      bacterial and fungal communities by sequencing bacterial 16S rRNA gene and fungal
      ITS data. Meanwhile, the beta-diversity was decomposed into two components:
      species replacement (species turnover) and nestedness to further explore the
      bacterial and fungal beta-diversity patterns and its causes. The results show
      that both bacterial and fungal beta-diversity were derived almost entirely from
      species turnover rather than from species nestedness. Distance-decay
      relationships confirmed that the geographic patterns of bacterial and fungal beta
      diversity were significantly different. Environmental factors had the dominant
      influence on both the bacterial and fungal beta-diversity and species turnover,
      however, the role of geographic distance varied across bacterial and fungal
      communities. Furthermore, both bacterial and fungal nestedness did not
      significantly respond to the environmental and geographic distance. Our findings
      suggest that the different response of bacterial and fungal species turnover to
      dispersal limitation and other, unknown processes may result in different
      biogeographic patterns of bacterial and fungal beta-diversity in the drylands of
      northwest China. Together, we highlight that the drivers of beta-diversity
      patterns vary between bacterial and fungal communities, and microbial beta
      diversity are driven by multiple factors in the drylands of northwest China.

PMID- 29176962
TI  - E2F1, a Novel Regulator of Metabolism.
AB  - In the past years, several lines of evidence have shown that cell cycle
      regulatory proteins also can modulate metabolic processes. The transcription
      factor E2F1 is a central player involved in cell cycle progression, DNA-damage
      response, and apoptosis. Its crucial role in the control of cell fate has been
      extensively studied and reviewed before; however, here, we focus on the
      participation of E2F1 in the regulation of metabolism. We summarize recent
      findings about the cell cycle-independent roles of E2F1 in various tissues that
      contribute to global metabolic homeostasis and highlight that E2F1 activity is
      increased during obesity. Finally, coming back to the pivotal role of E2F1 in
      cancer development, we discuss how E2F1 links cell cycle progression with
      different metabolic adaptations required for cell growth and survival.

PMID- 29176964
TI  - Only Acyl Carrier Protein 1 (AcpP1) Functions in Pseudomonas aeruginosa Fatty
      Acid Synthesis.
AB  - The genome of Pseudomonas aeruginosa contains three open reading frames, PA2966,
      PA1869, and PA3334, which encode putative acyl carrier proteins, AcpP1, AcpP2,
      and AcpP3, respectively. In this study, we found that, although these apo-ACPs
      were successfully phosphopantetheinylated by P. aeruginosa phosphopantetheinyl
      transferase (PcpS) and all holo-forms of these proteins could be acylated by
      Vibrio harveyi acyl-ACP synthetase (AasS), only AcpP1 could be used as a
      substrate for the synthesis of fatty acids, catalyzed by P. aeruginosa cell free
      extracts in vitro, and only acpP1 gene could restore growth in the Escherichia
      coliacpP mutant strain CY1877. And P. aeruginosaacpP1 could not be deleted, while
      disruption of acpP2 or acpP3 in the P. aeruginosa genome allowed mutant strains
      to grow as well as the wild type strain. These findings confirmed that only P.
      aeruginosa AcpP1 functions in fatty acid biosynthesis, and that acpP2 and acpP3
      do not play roles in the fatty acid synthetic pathway. Moreover, disruption of
      acpP2 and acpP3 did not affect the ability of P. aeruginosa to produce N
      acylhomoserine lactones (AHL), but replacement of P. aeruginosaacpP1 with E.
      coliacpP caused P. aeruginosa to reduce the production of AHL molecules, which
      indicated that neither P. aeruginosa AcpP2 nor AcpP3 can act as a substrate for
      synthesis of AHL molecules in vivo. Furthermore, replacement of acpP1 with E.
      coliacpP reduced the ability of P. aeruginosa to produce some exo-products and
      abolished swarming motility in P. aeruginosa.

PMID- 29176965
TI  - Down Modulation of Host Immune Response by Amino Acid Repeats Present in a
      Trypanosoma cruzi Ribosomal Antigen.
AB  - Several antigens from Trypanosoma cruzi, the causative agent of Chagas disease
      (CD), contain amino acid repeats identified as targets of the host immune
      response. Ribosomal proteins containing an Ala, Lys, Pro-rich repeat domain are
      among the T. cruzi antigens that are strongly recognized by antibodies from CD
      patients. Here we investigated the role of amino acid repeats present in the T.
      cruzi ribosomal protein L7a, by immunizing mice with recombinant versions of the
      full-length protein (TcRpL7a), as well as with truncated versions containing only
      the repetitive (TcRpL7aRep) or the non-repetitive domains (TcRpL7aDeltaRep). Mice
      immunized with full-length TcRpL7a produced high levels of IgG antibodies against
      the complete protein as well as against the repeat domain, whereas mice immunized
      with TcRpL7aDeltaRep or TcRpL7aRep produced very low levels or did not produce
      IgG antibodies against this antigen. Also in contrast to mice immunized with the
      full-length TcRpL7a, which produced high levels of IFN-gamma, only low levels of
      IFN-gamma or no IFN-gamma were detected in cultures of splenocytes derived from
      mice immunized with truncated versions of the protein. After challenging with
      trypomastigotes, mice immunized with the TcRpL7a were partially protected against
      the infection whereas immunization with TcRpL7aDeltaRep did not alter parasitemia
      levels compared to controls. Strikingly, mice immunized with TcRpL7aRep displayed
      an exacerbated parasitemia compared to the other groups and 100% mortality after
      infection. Analyses of antibody production in mice that were immunized with
      TcRpL7aRep prior to infection showed a reduced humoral response to parasite
      antigens as well as against an heterologous antigen. In vitro proliferation
      assays with mice splenocytes incubated with different mitogens in the presence of
      TcRpL7aRep resulted in a drastic inhibition of B-cell proliferation and antibody
      production. Taken together, these results indicate that the repeat domain of
      TcRpL7a acts as an immunosuppressive factor that down regulates the host B-cell
      response against parasite antigens favoring parasite multiplication in the
      mammalian host.

PMID- 29176960
TI  - From Sea to Shining Sea and the Great Plains to Patagonia: A Review on Current
      Knowledge of Diabetes Mellitus in Hispanics/Latinos in the US and Latin America.
AB  - The past two decades have witnessed many advances in the prevention, treatment,
      and control of diabetes mellitus (DM) and its complications. Increased screening
      has led to a greater recognition of type 2 diabetes mellitus (type 2 DM) and
      prediabetes; however, Hispanics/Latinos, the largest minority group in the US,
      have not fully benefited from these advances. The Hispanic/Latino population is
      highly diverse in ancestries, birth places, cultures, languages, and
      socioeconomic backgrounds, and it populates most of the Western Hemisphere. In
      the US, the prevalence of DM varies among Hispanic/Latino heritage groups, being
      higher among Mexicans, Puerto Ricans, and Dominicans, and lower among South
      Americans. The risk and prevalence of diabetes among Hispanics/Latinos are
      significantly higher than in non-Hispanic Whites, and nearly 40% of
      Hispanics/Latinos with diabetes have not been formally diagnosed. Despite these
      striking facts, the representation of Hispanics/Latinos in pharmacological and
      non-pharmacological clinical trials has been suboptimal, while the prevalence of
      diabetes in these populations continues to rise. This review will focus on the
      epidemiology, etiology and prevention of type 2 DM in populations of Latin
      American origin. We will set the stage by defining the terms Hispanic, Latino,
      and Latin American, explaining the challenges identifying Hispanics/Latinos in
      the scientific literature and databases, describing the epidemiology of diabetes
      including type 2 DM and gestational diabetes mellitus (GDM)-and cardiovascular
      risk factors in Hispanics/Latinos in the US and Latin America, and discussing
      trends, and commonalities and differences across studies and populations,
      including methodology to ascertain diabetes. We will discuss studies on
      mechanisms of disease, and research on prevention of type 2 DM in
      Hispanics/Latinos, including women with GDM, youth and adults; and finalize with
      a discussion on lessons learned and opportunities to enhance research, and,
      consequently, clinical care oriented toward preventing type 2 DM in
      Hispanics/Latinos in the US and Latin America.

PMID- 29176966
TI  - Induction of Tyrosine Phosphorylation of UV-Activated EGFR by the Beta-Human
      Papillomavirus Type 8 E6 Leads to Papillomatosis.
AB  - Epidemiological evidence is accumulating that beta-human papillomaviruses (HPV)
      synergize with UV-light in the development of precancerous actinic keratosis, and
      cutaneous squamous cell carcinomas (cSCC), one of the most common cancers in the
      Caucasian population. We previously demonstrated the tumorigenic activity of beta
      HPV type 8 (HPV8) in the skin of transgenic mice and its cooperation with UV
      light. Analysis of underlying mechanisms now showed that in keratinocytes
      expressing the HPV8E6 protein a transient increase of tyrosine phosphorylated
      epidermal growth factor receptor (EGFR) in response to UV-irradiation occurred,
      while EGFR tyrosine phosphorylation, i.e., receptor tyrosine kinase (RTK)
      activity was hardly affected in empty vector control cells. FACS and
      immunofluorescences revealed that the EGFR was internalized into early endosomes
      in response to UV-exposure in both, HPV8E6 positive and in control cells, yet
      with a higher rate in the presence of HPV8E6. Moreover, only in HPV8E6 expressing
      keratinocytes the EGFR was further sorted into CD63+ intraluminal vesicles,
      indicative for trafficking to late endosomes. The latter requires the
      ubiquitination of the EGFR, and in correlation, we could show that only in HPV8E6
      positive keratinocytes the EGFR was ubiquitinated upon UV-exposure. HPV8E6 and
      tyrosine phosphorylated EGFR directly interacted which was enhanced by UV
      irradiation. The treatment of K14-HPV8E6 transgenic mice with Canertinib, an
      inhibitor of the RTK-activity of the EGFR, suppressed skin papilloma growth in
      response to UV-irradiation. This confirms the crucial role of the RTK-activity of
      the EGFR in HPV8E6 and UV-mediated papillomatosis in transgenic mice. Taken
      together, our results demonstrate that HPV8E6 alters the signaling of the UV
      activated EGFR and this is a critical step in papilloma formation in response to
      UV-light in transgenic mice. Our results provide a molecular basis how a beta-HPV
      type may support early steps of skin tumor formation in cooperation with UV
      light.

PMID- 29176967
TI  - Reporter-Based Assays for High-Throughput Drug Screening against Mycobacterium
      abscessus.
AB  - Mycobacterium abscessus is a non-tuberculous mycobacterium that causes pulmonary
      and non-pulmonary infections. M. abscessus is resistant to many chemotherapeutic
      agents and the current treatment options show poor clinical outcomes. Thus, there
      is a dire need to find new antimicrobials effective at killing M. abscessus.
      Screening drug libraries to identify potential antimicrobials has been impeded by
      the lack of validated HTS assays for M. abscessus. In this study, we developed
      two 384-well high-throughput screening assays using fluorescent and
      bioluminescent reporter strains of M. abscessus for drug discovery. Optimization
      of inoculum size, incubation time and the volume-per-well based on Z-factor and
      signal intensity yielded two complementary, robust tools for M. abscessus drug
      discovery with Z-factor > 0.8. The MIC of known drugs, amikacin and
      clarithromycin, as determined by bioluminescence was in agreement with the
      published MIC values. A proof-of-concept screen of 2,093 natural product-inspired
      compounds was conducted using the 384-well bioluminescent assay to identify novel
      scaffolds active against M. abscessus. Five active "hit" compounds identified in
      this pilot screen were confirmed and characterized by a CFU assay and MIC
      determination. Overall, we developed and validated a 384-well screen that offers
      simple, sensitive and fast screening of compounds for activity against this
      emerging pathogen. To our knowledge, this is the first reporter-based high
      throughput screening study aimed at M. abscessus drug discovery.

PMID- 29176968
TI  - Uninterrupted Expression of CmSIT1 in a Sclerotial Parasite Coniothyrium minitans
      Leads to Reduced Growth and Enhanced Antifungal Ability.
AB  - Coniothyrium minitans is an important mycoparasite of Sclerotinia sclerotiorum.
      In addition, it also produces small amounts of antifungal substances. ZS-1TN1812,
      an abnormal mutant, was originally screened from a T-DNA insertional library.
      This mutant showed abnormal growth phenotype and could significantly inhibit the
      growth of S. sclerotiorum when dual-cultured on a PDA plate. When spraying the
      filtrate of ZS-1TN1812 on the leaves of rapeseed, S. sclerotiorum infection was
      significantly inhibited, suggesting that the antifungal substances produced by
      this mutant were effective on rapeseed leaves. The thermo-tolerant antifungal
      substances could specifically suppress the growth of S. sclerotiorum, but could
      not significantly suppress the growth of another fungus, Colletotrichum
      higginsianum. However, C. higginsianum was more sensitive to proteinous
      antibiotics than S. sclerotiorum. The T-DNA insertion in ZS-1TN1812 activated the
      expression of CmSIT1, a gene involved in siderophore-mediated iron transport. It
      was also determined that mutant ZS-1TN1812 produced hypha with high iron levels.
      In the wild-type strain ZS-1, CmSIT1 was expressed only when in contact with S.
      sclerotiorum, and consistent overexpression of CmSIT1 showed similar phenotypes
      as ZS-1TN1812. Therefore, activated expression of CmSIT1 leads to the enhanced
      antifungal ability, and CmSIT1 is a potential gene for improving the control
      ability of C. minitans.

PMID- 29176969
TI  - Chromobacterium violaceum Pathogenicity: Updates and Insights from Genome
      Sequencing of Novel Chromobacterium Species.
AB  - Chromobacterium violaceum is an abundant component of the soil and water
      microbiota in tropical and subtropical regions around the world. For many years,
      it was mainly known as a producer of violacein and as a reporter for the
      discovery of quorum sensing molecules. However, C. violaceum has recently emerged
      as an important model of an environmental opportunistic pathogen. Its high
      virulence in human infections and a mouse infection model involves the possession
      of several predicted virulence traits, including two type III secretion systems
      (T3SSs). In this article, in addition to providing an update on the new clinical
      cases of human C. violaceum infections, we will focus on recent advances in
      understanding the molecular mechanisms regarding C. violaceum pathogenesis. It
      has been demonstrated that the C. violaceum Cpi-1 T3SS plays a pivotal role in
      interaction with host cells. It is required for the secretion of effector
      proteins and is the agonist recognized by the Nod-like receptor CARD domain
      containing protein 4 (NLRC4) inflammasome from innate immune cells. Pyroptosis
      and its release of hepatocytes for killing by neutrophils are key events required
      for the clearance of C. violaceum. Given the prominent role of T3SSs in C.
      violaceum virulence, we examine their occurrence in the Chromobacterium genus,
      taking advantage of several draft genome sequences of Chromobacterium species
      that have recently become available. Our finding that the Cpi-1 T3SS is
      widespread among Chromobacterium species points toward the pathogenic potential
      of this genus for humans or to novel roles of the T3SS in the interaction of
      Chromobacterium species with other organisms.

PMID- 29176970
TI  - The Mitogen-Activated Protein Kinase CgMK1 Governs Appressorium Formation,
      Melanin Synthesis, and Plant Infection of Colletotrichum gloeosporioides.
AB  - The fungus Colletotrichum gloeosporiodes infects plant hosts with a specialized
      cell called an appressorium, which is melanized and required for plant cell wall
      penetration. Here, we show that the mitogen-activated protein kinase CgMK1
      governs appressorium formation and virulence in the poplar anthracnose fungus C.
      gloeosporioides. Deletion of CgMK1 impairs aerial hyphal growth and biomass
      accumulation, and CgMK1 is responsible for the expression of melanin biosynthesis
      associated genes. CgMK1 deletion mutants are unable to form appressorium and lose
      the capacity to colonize either wounded or unwounded poplar leaves, leading to
      loss of virulence. We demonstrate that the exogenous application of cAMP fails to
      restore defective appressorium formation in the CgMK1 deletion mutants,
      suggesting that CgMK1 may function downstream or independent of a cAMP-dependent
      signal for appressorium formation. Moreover, CgMK1 mutants were sensitive to high
      osmosis, indicating that CgMK1 plays an important role in stress response. We
      conclude that CgMK1 plays a vital role in regulating appressorium formation,
      melanin biosynthesis, and virulence in C. gloeosporiodes.

PMID- 29176971
TI  - Occurrence of Extended Spectrum beta-Lactamases, KPC-Type, and MCR-1.2-Producing
      Enterobacteriaceae from Wells, River Water, and Wastewater Treatment Plants in
      Oltrepo Pavese Area, Northern Italy.
AB  - To evaluate the water compartment antibiotic-resistance contamination rates, 11
      wells, five streams, and four treatment plants located in the Oltrepo Pavese area
      were screened for the presence of third generation cephalosporins resistant Gram
      negative bacteria. Enterobacteriaceae were also characterized for the Extended
      Spectrum-beta-Lactamases (ESBLs), carbapenemases, and mcr-1 genes presence. From
      December 2014 to November 2015, 246 water samples were filtered, plated on Plate
      Count Agar, MacConkey Agar, and MacConkey Agar with cefotaxime. Isolates were
      species identified using AutoSCAN-4-System and ESBLs, carbapenemases, and
      colistin resistance determinants were characterized by PCR, sequencing, and
      microarray. Plasmid conjugative transfer experiments, PCR-based Replicon typing,
      Pulsed-Field Gel Electrophoresis, Multi-Locus-Sequence-Typing, and in-silico
      plasmid characterization were performed. A total of 132 enterobacteria isolates
      grew on MacConkey agar with cefotaxime: 82 (62.1%) were obtained from streams, 41
      (31.1%) from treatment plants, and 9 (6.8%) from wells. Thirty out of 132 (22.7%)
      isolates, mainly belonging to Escherichia coli (n = 15) species, showed a
      synergic effect with piperacillin-tazobactam. A single ESBL gene of blaCTX-M-type
      was identified in 19/30 isolates. In further two E. coli strains, a blaCTX-M-1
      gene co-existed with a blaSHV-type ESBL determinant. A blaSHV-12 gene was
      detected in two isolates of E. coli (n = 1) and Klebsiella oxytoca (n = 1), while
      any ESBL determinant was ascertained in seven Yersinia enterocolitica strains. A
      blaDHA-type gene was detected in a cefoxitin resistant Y. enterocolitica from a
      stream. Interestingly, two Klebsiella pneumoniae strains of ST307 and ST258,
      collected from a well and a wastewater treatment plant, resulted KPC-2, and KPC-3
      producers, respectively. Moreover, we report the first detection of mcr-1.2 ST10
      E. coli on a conjugative IncX4 plasmid (33.303 bp in size) from a stream of
      Oltrepo Pavese (Northern Italy). Both ESBLs E. coli and ESBLs/carbapenemase
      producing K. pneumoniae strains showed clonal heterogeneity by Pulsed-Field Gel
      Electrophoresis and Multi-Locus-Sequence-Typing. During one-year study and taking
      in account the whole Gram-negative bacterial population, an average percentage of
      cefotaxime resistance of 69, 32, and 10.3% has been obtained for the wastewater
      treatment plants, streams, and wells, respectively. These results, of concern for
      public health, highlight the need to improve hygienic measures to reduce the load
      of discharged bacteria with emerging resistance mechanisms.

PMID- 29176972
TI  - Interleukin-4 Receptor Alpha: From Innate to Adaptive Immunity in Murine Models
      of Cutaneous Leishmaniasis.
AB  - The interleukin (IL)-4 receptor alpha (IL-4Ralpha), ubiquitously expressed on
      both innate and adaptive immune cells, controls the signaling of archetypal type
      2 immune regulators; IL-4 and IL-13, which elicit their signaling action by the
      type 1 IL-4Ralpha/gamma common and/or the type 2 IL-4Ralpha/IL-13Ralpha
      complexes. Global gene-deficient mouse models targeting IL-4, IL-13, or the IL
      4Ralpha chain, followed by the development of conditional mice and generation of
      important cell-type-specific IL-4Ralpha-deficient mouse models, were indeed
      critical to gaining in-depth understanding of detrimental T helper (Th) 2
      mechanisms in type 1-controlled diseases. A primary example being cutaneous
      leishmaniasis, which is caused by the protozoan parasite Leishmania major, among
      others. The disease is characterized by localized self-healing cutaneous lesions
      and necrosis for which, currently, not a single vaccine has made it to a stage
      that can be considered effective. The spectrum of human leishmaniasis belongs to
      the top 10 infectious diseases according to the World Health Organization. As
      such, 350 million humans are at risk of infection and disease, with an incidence
      of 1.5-2 million new cases being reported annually. A major aim of our research
      is to identify correlates of host protection and evasion, which may aid in
      vaccine design and therapeutic interventions. In this review, we focus on the
      immune-regulatory role of the IL-4Ralpha chain from innate immune responses to
      the development of beneficial type 1 and detrimental type 2 adaptive immune
      responses during cutaneous Leishmania infection. We discuss the cell-specific
      requirements of the IL-4Ralpha chain on crucial innate immune cells during L.
      major infection, including, IL-4Ralpha-responsive skin keratinocytes,
      macrophages, and neutrophils, as well as dendritic cells (DCs). The latter,
      contributing to one of the paradigm shifts with respect to the role of IL-4
      instructing DCs in vivo, to promote Th1 responses against L. major. Finally, we
      extend these innate responses and mechanisms to control of adaptive immunity and
      the effect of IL-4Ralpha-responsiveness on T and B lymphocytes orchestrating the
      development of CD4+ Th1/Th2 and B effector 1/B effector 2 B cells in response to
      L. major infection in the murine host.

PMID- 29176973
TI  - Serum and Extracellular Vesicle MicroRNAs miR-423, miR-199, and miR-93* As
      Biomarkers for Acute Graft-versus-Host Disease.
AB  - Acute graft-versus-host disease (aGvHD) is a major cause of adverse outcome in
      hematopoietic stem cell transplantation (HSCT), with a high incidence (20-50%). A
      novel, non-invasive diagnostic test to predict for prevalence and severity would
      enable improved prophylaxis and reduce morbidity. Circulatory microRNAs (miRNAs)
      miR-423, miR-199, miR-93*, and miR-377 have previously been associated with aGvHD
      in post-HSCT patient plasma, but validation is lacking and their expression
      within extracellular vesicles (EVs) has not been explored. This study replicated
      elevated serum expression of miR-423 (p < 0.001), miR-199 (p = 0.04), miR-93* (p
      < 0.001), and miR-377 (p = 0.03) in aGvHD, using a prognostic cohort of day 14
      (D14) post-HSCT patient samples (n = 81). Expression also associated with disease
      severity. Further analysis at aGvHD diagnosis in an independent cohort (n = 65)
      confirmed high miR-423 (p = 0.02), miR-199 (p = 0.007), and miR-93* (p = 0.004)
      expression at disease onset. Investigation of expression patterns during early
      HSCT sequential timepoints (pre-HSCT to D28) identified elevated miRNAs at D7
      post-HSCT in all transplant patients. In a novel investigation of miRNA
      expression in serum EVs (n = 15), miR-423 (p = 0.09), miR-199 (p = 0.008), and
      miR-93* (p = 0.001) levels were lower at D14 in patients who later developed
      aGvHD, and this was replicated for miR-423 (p = 0.02) and miR-199 (p = 0.04) (n =
      47). Comparing serum to circulating EVs, at D14 patients remaining aGvHD-free had
      higher expression of miR-423 (p = 0.03), miR-199 (p = 0.009), and miR-93* (p =
      0.002) in the EV fraction. Results verify the capacity for circulating miR-423,
      miR-199, and miR-93* as diagnostic and prognostic aGvHD biomarkers. The novel
      finding of their differential expression in EVs suggests a potential role in
      aGvHD etiology.

PMID- 29176974
TI  - Inhibition of Epithelial TNF-alpha Receptors by Purified Fruit Bromelain
      Ameliorates Intestinal Inflammation and Barrier Dysfunction in Colitis.
AB  - Activation of the TNF-alpha receptor (TNFR) leads to an inflammatory response,
      and anti-TNF therapy has been administered to reduce inflammation symptoms and
      heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex
      natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory
      effects. This study aimed to investigate the effect of purified fruit bromelain
      (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was
      established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic
      acid. Expression of TNFR1 and TNFR2 was measured by quantitative RT-PCR and
      western blotting. The effect of PFB on colitis was evaluated by examining the
      inflammatory response and intestinal epithelial barrier function. Our results
      showed that both TNFR1 and TNFR2 expression were significantly increased in a
      colitis model, and the increase was significantly reversed by PFB. Colitis
      symptoms, including infiltration of inflammatory cells, cytokine profiles,
      epithelial cell apoptosis, and epithelial tight junction barrier dysfunction were
      significantly ameliorated by PFB. Compared with fruit bromelain and stem
      bromelain complex, the inhibition of TNFR2 induced by PFB was stronger than that
      exhibited on TNFR1. These results indicate that PFB showed a stronger selective
      inhibitory effect on TNFR2 than TNFR1. In other words, purification of fruit
      bromelain increases its selectivity on TNFR2 inhibition. High expression of
      epithelial TNFRs in colitis was significantly counteracted by PFB, and PFB
      induced TNFR inhibition ameliorated colitis symptoms. These results supply novel
      insights into potential IBD treatment by PFB.

PMID- 29176976
TI  - Engineering Specificity and Function of Therapeutic Regulatory T Cells.
AB  - Adoptive therapy with polyclonal regulatory T cells (Tregs) has shown efficacy in
      suppressing detrimental immune responses in experimental models of autoimmunity
      and transplantation. The lack of specificity is a potential limitation of Treg
      therapy, as studies in mice have demonstrated that specificity can enhance the
      therapeutic potency of Treg. We will discuss that vectors encoding T cell
      receptors or chimeric antigen receptors provide an efficient gene-transfer
      platform to reliably produce Tregs of defined antigen specificity, thus
      overcoming the considerable difficulties of isolating low-frequency, antigen
      specific cells that may be present in the natural Treg repertoire. The recent
      observations that Tregs can polarize into distinct lineages similar to the Th1,
      Th2, and Th17 subsets described for conventional T helper cells raise the
      possibility that Th1-, Th2-, and Th17-driven pathology may require matching Treg
      subsets for optimal therapeutic efficacy. In the future, genetic engineering may
      serve not only to enforce FoxP3 expression and a stable Treg phenotype but it may
      also enable the expression of particular transcription factors that drive
      differentiation into defined Treg subsets. Together, established and recently
      developed gene transfer and editing tools provide exciting opportunities to
      produce tailor-made antigen-specific Treg products with defined functional
      activities.

PMID- 29176975
TI  - Targeting Cannabinoid Signaling in the Immune System: "High"-ly Exciting
      Questions, Possibilities, and Challenges.
AB  - It is well known that certain active ingredients of the plants of Cannabis genus,
      i.e., the "phytocannabinoids" [pCBs; e.g., (-)-trans-Delta9-tetrahydrocannabinol
      (THC), (-)-cannabidiol, etc.] can influence a wide array of biological processes,
      and the human body is able to produce endogenous analogs of these substances
      ["endocannabinoids" (eCB), e.g., arachidonoylethanolamine (anandamide, AEA), 2
      arachidonoylglycerol (2-AG), etc.]. These ligands, together with multiple
      receptors (e.g., CB1 and CB2 cannabinoid receptors, etc.), and a complex enzyme
      and transporter apparatus involved in the synthesis and degradation of the
      ligands constitute the endocannabinoid system (ECS), a recently emerging
      regulator of several physiological processes. The ECS is widely expressed in the
      human body, including several members of the innate and adaptive immune system,
      where eCBs, as well as several pCBs were shown to deeply influence immune
      functions thereby regulating inflammation, autoimmunity, antitumor, as well as
      antipathogen immune responses, etc. Based on this knowledge, many in vitro and in
      vivo studies aimed at exploiting the putative therapeutic potential of
      cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple
      sclerosis) or in organ transplantation, and to dissect the complex immunological
      effects of medical and "recreational" marijuana consumption. Thus, the objective
      of the current article is (i) to summarize the most recent findings of the field;
      (ii) to highlight the putative therapeutic potential of targeting cannabinoid
      signaling; (iii) to identify open questions and key challenges; and (iv) to
      suggest promising future directions for cannabinoid-based drug development.

PMID- 29176978
TI  - Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine
      Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest
      Specific 6.
AB  - The Tyro3, Axl, and Mertk (TAM) receptors are homologous type I receptor tyrosine
      kinases that have critical functions in the clearance of apoptotic cells in
      multicellular organisms. TAMs are activated by their endogenous ligands, growth
      arrest-specific 6 (Gas6), and protein S (Pros1), that function as bridging
      molecules between externalized phosphatidylserine (PS) on apoptotic cells and the
      TAM ectodomains. However, the molecular mechanisms by which Gas6/Pros1 promote
      TAM activation remains elusive. Using TAM/IFNgammaR1 reporter cell lines to
      monitor functional TAM activity, we found that Gas6 activity was exquisitely
      dependent on vitamin K-mediated gamma-carboxylation, whereby replacing vitamin K
      with anticoagulant warfarin, or by substituting glutamic acid residues involved
      in PS binding, completely abrogated Gas6 activity as a TAM ligand. Furthermore,
      using domain and point mutagenesis, Gas6 activity also required both an intact
      Gla domain and intact EGF-like domains, suggesting these domains function
      cooperatively in order to achieve TAM activation. Despite the requirement of
      gamma-carboxylation and the functional Gla domain, non-gamma-carboxylated Gas6
      and Gla deletion/EGF-like domain deletion mutants still retained their ability to
      bind TAMs and acted as blocking decoy ligands. Finally, we found that distinct
      sources of PS-positive cells/vesicles (including apoptotic cells, calcium-induced
      stressed cells, and exosomes) bound Gas6 and acted as cell-derived or exosome
      derived ligands to activate TAMs. Taken together, our findings indicate that PS
      is indispensable for TAM activation by Gas6, and by inference, provides new
      perspectives on how PS, regulates TAM receptors and efferocytosis.

PMID- 29176979
TI  - US6 Gene Deletion in Herpes Simplex Virus Type 2 Enhances Dendritic Cell Function
      and T Cell Activation.
AB  - Herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) produce lifelong
      infections that are associated with frequent asymptomatic or clinically apparent
      reactivation. Importantly, HSV express multiple virulence factors that negatively
      modulate innate and adaptive immune components. Notably, HSV interfere with
      dendritic cell (DC) viability and function, likely hindering the capacity of the
      host to mount effective immunity against these viruses. Recently, an HSV-2 virus
      that was deleted in glycoprotein D was engineered (designated DeltagD-2). The
      virus is propagated on a complementing cell line that expresses HSV-1 gD, which
      permits a single round of viral replication. DeltagD-2 is safe, immunogenic, and
      provided complete protection against vaginal or skin challenges with HSV-1 and
      HSV-2 in murine models. Here, we sought to assess the interaction of DeltagD-2
      with DCs and found that, in contrast to wild-type (WT) virus which induces DC
      apoptosis, DeltagD-2 promoted their migration and capacity to activate naive CD8+
      and CD4+ T cells in vitro and in vivo. Furthermore, DCs exposed to the WT and
      DeltagD-2 virus experienced different unfolded protein responses. Mice primed
      with DCs infected with DeltagD-2 in vitro displayed significantly reduced
      infection and pathology after genital challenge with virulent HSV-2 compared to
      non-primed mice, suggesting that DCs play a role in the immune response to the
      vaccine strain.

PMID- 29176980
TI  - iRAGu: A Novel Inducible and Reversible Mouse Model for Ubiquitous Recombinase
      Activity.
AB  - Developing lymphocytes express the recombination activating genes (RAGs) 1 and 2
      products that form a site specific recombinase complex (RAG), introducing double
      strand DNA breaks (DSBs) at recombination signal sequences (RSSs) flanking the V,
      D, and J gene segments in the antigen receptor loci. The subsequent steps in the
      reaction consist in the ligation of DSBs by ubiquitous enzymes of the non
      homologous end joining DNA repair pathway. This mutagenesis process is
      responsible for the generation of the very large clonal diversity of T and B
      lymphocytes, itself allowing the recognition of a virtually open-ended antigenic
      universe. Sequences resembling RSS are found at high frequency all over the
      genome, and involved in RAG mediated illegitimate recombination and
      translocations. Hence, natural and induced ectopic activity of RAG is a threat to
      the genome only recently underscored. Here, we report and characterize a novel
      mouse transgenic system for which ubiquitous expression of the recombinase is
      inducible. In this system, the RAG1 protein is constitutively expressed and
      functional, while the RAG2 protein, coupled to the estrogen receptor, becomes
      functionally active upon 4-hydroxytamoxifen (TAM) administration. We describe two
      transgenic lines. The first one, when introgressed into an endogenous Rag2-/-
      genetic background is faithfully recapitulating lymphocyte development,
      repertoire dynamics and cryptic rearrangements, in a TAM-dependent manner. In
      this model, deprivation of TAM is followed by lymphocyte development arrest,
      evidencing the reversibility of the system. The second transgenic line is leaky,
      as the transgenes promote lymphocyte differentiation in absence of TAM treatment.
      Upon TAM-induction defects in lymphocytes composition and global health reveals
      the deleterious effect of uncontrolled RAG activity. Overall, this novel
      transgenic model provides a tool where RAG activity can be specifically
      manipulated to assess the dynamics of lymphocyte differentiation and the
      challenges imposed by the recombinase on the vertebrate genome.

PMID- 29176977
TI  - Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia.
AB  - Macrophages and microglia play crucial roles during central nervous system
      development, homeostasis and acute events such as infection or injury. The
      diverse functions of tissue macrophages and microglia are mirrored by equally
      diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2
      macrophages has been widely used. However, the complexity of macrophage function
      can only be achieved by the existence of varied, plastic and tridimensional
      macrophage phenotypes. Understanding how tissue macrophages integrate
      environmental signals via molecular programs to define pathogen/injury
      inflammatory responses provides an opportunity to better understand the
      multilayered nature of macrophages, as well as target and modulate cellular
      programs to control excessive inflammation. This is particularly important in MS
      and other neuroinflammatory diseases, where chronic inflammatory macrophage and
      microglial responses may contribute to pathology. Here, we perform a
      comprehensive review of our current understanding of how molecular pathways
      modulate tissue macrophage phenotype, covering both classic pathways and the
      emerging role of microRNAs, receptor-tyrosine kinases and metabolism in
      macrophage phenotype. In addition, we discuss pathway parallels in microglia,
      novel markers helpful in the identification of peripheral macrophages versus
      microglia and markers linked to their phenotype.

PMID- 29176981
TI  - Bifidobacterium infantis Potentially Alleviates Shrimp Tropomyosin-Induced
      Allergy by Tolerogenic Dendritic Cell-Dependent Induction of Regulatory T Cells
      and Alterations in Gut Microbiota.
AB  - Shellfish is one of the major allergen sources worldwide, and tropomyosin (Tm) is
      the predominant allergic protein in shellfish. Probiotics has been appreciated
      for its beneficial effects on the host, including anti-allergic and anti
      inflammatory effects, although the underlying mechanisms were not fully
      understood. In this study, oral administration of probiotic strain
      Bifidobacterium infantis 14.518 (Binf) effectively suppressed Tm-induced allergic
      response in a mouse model by both preventive and therapeutic strategies. Further
      results showed that Binf stimulated dendritic cells (DCs) maturation and CD103+
      tolerogenic DCs accumulation in gut-associated lymphoid tissue, which
      subsequently induced regulatory T cells differentiation for suppressing Th2
      biased response. We also found that Binf regulates the alterations of gut
      microbiota composition. Specifically, the increase of Dorea and decrease of
      Ralstonia is highly correlated with Th2/Treg ratio and may contribute to
      alleviating Tm-induced allergic responses. Our findings provide molecular insight
      into the application of Binf in alleviating food allergy and even gut immune
      homeostasis.

PMID- 29176982
TI  - Suppressor of Cytokine Signaling 3 in Macrophages Prevents Exacerbated
      Interleukin-6-Dependent Arginase-1 Activity and Early Permissiveness to
      Experimental Tuberculosis.
AB  - Suppressor of cytokine signaling 3 (SOCS3) is a feedback inhibitor of interleukin
      (IL)-6 signaling in macrophages. In the absence of this molecule, macrophages
      become extremely prone to an IL-6-dependent expression of arginase-1 (Arg1) and
      nitric oxide synthase (NOS)2, the prototype markers for alternative or classical
      macrophage activation, respectively. Because both enzymes are antipodean
      macrophage effector molecules in Mycobacterium tuberculosis (Mtb) infection, we
      assessed the relevance of SOCS3 for macrophage activation during experimental
      tuberculosis using macrophage-specific SOCS3-deficient (LysMcreSOCS3loxP/loxP)
      mice. Aerosol infection of LysMcreSOCS3loxP/loxP mice resulted in remarkably
      higher bacterial loads in infected lungs and exacerbated pulmonary inflammation.
      This increased susceptibility to Mtb infection was accompanied by enhanced levels
      of both classical and alternative macrophage activation. However, high Arg1
      expression preceded the increased induction of NOS2 and at early time points of
      infection mycobacteria were mostly found in cells positive for Arg1. This
      sequential activation of Arg1 and NOS2 expression in LysMcreSOCS3loxP/loxP mice
      appears to favor the initial replication of Mtb particularly in Arg1-positive
      cells. Neutralization of IL-6 in Mtb-infected LysMcreSOCS3loxP/loxP mice reduced
      arginase activity and restored control of mycobacterial replication in
      LysMcreSOCS3loxP/loxP mice. Our data reveal an unexpected role of SOCS3 during
      experimental TB: macrophage SOCS3 restrains early expression of Arg1 and helps
      limit Mtb replication in resident lung macrophages, thereby limiting the growth
      of mycobacteria. Together, SOCS3 keeps IL-6-dependent divergent macrophage
      responses such as Nos2 and Arg1 expression under control and safeguard protective
      macrophage effector mechanisms.

PMID- 29176983
TI  - Mucosal-Associated Invariant T Cells: New Insights into Antigen Recognition and
      Activation.
AB  - Mucosal-associated invariant T (MAIT) cells, a novel subpopulation of innate-like
      T cells that express an invariant T cell receptor (TCR)alpha chain and a diverse
      TCRbeta chain, can recognize a distinct set of small molecules, vitamin B
      metabolites, derived from some bacteria, fungi but not viruses, in the context of
      an evolutionarily conserved major histocompatibility complex-related molecule 1
      (MR1). This implies that MAIT cells may play unique and important roles in host
      immunity. Although viral antigens are not recognized by this limited TCR
      repertoire, MAIT cells are known to be activated in a TCR-independent mechanism
      during some viral infections, such as hepatitis C virus and influenza virus. In
      this article, we will review recent works in MAIT cell antigen recognition,
      activation and the role MAIT cells may play in the process of bacterial and viral
      infections and pathogenesis of non-infectious diseases.

PMID- 29176984
TI  - The Dynamic Interplay between HIV-1, SAMHD1, and the Innate Antiviral Response.
AB  - The innate immune response constitutes the first cellular line of defense against
      initial HIV-1 infection. Immune cells sense invading virus and trigger signaling
      cascades that induce antiviral defenses to control or eliminate infection.
      Professional antigen-presenting cells located in mucosal tissues, including
      dendritic cells and macrophages, are critical for recognizing HIV-1 at the site
      of initial exposure. These cells are less permissive to HIV-1 infection compared
      to activated CD4+ T-cells, which is mainly due to host restriction factors that
      serve an immediate role in controlling the establishment or spread of viral
      infection. However, HIV-1 can exploit innate immune cells and their cellular
      factors to avoid detection and clearance by the host immune system. Sterile alpha
      motif and HD-domain containing protein 1 (SAMHD1) is the mammalian
      deoxynucleoside triphosphate triphosphohydrolase responsible for regulating
      intracellular dNTP pools and restricting the replication of HIV-1 in non-dividing
      myeloid cells and quiescent CD4+ T-cells. Here, we review and analyze the latest
      literature on the antiviral function of SAMHD1, including the mechanism of HIV-1
      restriction and the ability of SAMHD1 to regulate the innate immune response to
      viral infection. We also provide an overview of the dynamic interplay between HIV
      1, SAMHD1, and the cell-intrinsic antiviral response to elucidate how SAMHD1
      modulates HIV-1 infection in non-dividing immune cells. A more complete
      understanding of SAMHD1's role in the innate immune response to HIV-1 infection
      may help develop stratagems to enhance its antiviral effects and to more
      efficiently block HIV-1 replication and avoid the pathogenic result of viral
      infection.

PMID- 29176985
TI  - Mucosal IgA Responses: Damaged in Established HIV Infection-Yet, Effective Weapon
      against HIV Transmission.
AB  - HIV infection not only destroys CD4+ T cells but also inflicts serious damage to
      the B-cell compartment, such as lymphadenopathy, destruction of normal B-cell
      follicle architecture, polyclonal hypergammaglobulinemia, increased apoptosis of
      B cells, and irreversible loss of memory B-cell responses with advanced HIV
      disease. Subepithelial B cells and plasma cells are also affected, which results
      in loss of mucosal IgG and IgA antibodies. This leaves the mucosal barrier
      vulnerable to bacterial translocation. The ensuing immune activation in mucosal
      tissues adds fuel to the fire of local HIV replication. We postulate that
      compromised mucosal antibody defenses also facilitate superinfection of HIV
      positive individuals with new HIV strains. This in turn sets the stage for the
      generation of circulating recombinant forms of HIV. What can the mucosal B-cell
      compartment contribute to protect a healthy, uninfected host against mucosal HIV
      transmission? Here, we discuss proof-of-principle studies we have performed using
      passive mucosal immunization, i.e., topical administration of preformed anti-HIV
      monoclonal antibodies (mAbs) as IgG1, dimeric IgA1 (dIgA1), and dIgA2 isotypes,
      alone or in combination. Our data indicate that mucosally applied anti-HIV
      envelope mAbs can provide potent protection against mucosal transmission of
      simian-human immunodeficiency virus. Our review also discusses the induction of
      mucosal antibody defenses by active vaccination and potential strategies to
      interrupt the vicious cycle of bacterial translocation, immune activation, and
      stimulation of HIV replication in individuals with damaged mucosal barriers.

PMID- 29176987
TI  - Radiocarbon Dating of an Olive Tree Cross-Section: New Insights on Growth
      Patterns and Implications for Age Estimation of Olive Trees.
AB  - The age of living massive olive trees is often assumed to be between hundreds and
      even thousands of years. These estimations are usually based on the girth of the
      trunk and an extrapolation based on a theoretical annual growth rate. It is
      difficult to objectively verify these claims, as a monumental tree may not be cut
      down for analysis of its cross-section. In addition, the inner and oldest part of
      the trunk in olive trees usually rots, precluding the possibility of carting out
      radiocarbon analysis of material from the first years of life of the tree. In
      this work we present a cross-section of an olive tree, previously estimated to be
      hundreds of years old, which was cut down post-mortem in 2013. The cross-section
      was radiocarbon dated at numerous points following the natural growth pattern,
      which was made possible to observe by viewing the entire cross-section. Annual
      growth rate values were calculated and compared between different radii. The
      cross-section also revealed a nearly independent segment of growth, which would
      clearly offset any estimations based solely on girth calculations. Multiple piths
      were identified, indicating the beginning of branching within the trunk.
      Different radii were found to have comparable growth rates, resulting in similar
      estimates dating the piths to the 19th century. The estimated age of the piths
      represent a terminus ante quem for the age of the tree, as these are piths of
      separate branches. However, the tree is likely not many years older than the
      dated piths, and certainly not centuries older. The oldest radiocarbon-datable
      material in this cross-section was less than 200 years old, which is in agreement
      with most other radiocarbon dates of internal wood from living olive trees,
      rarely older than 300 years.

PMID- 29176986
TI  - Dissecting the Variations of Ripening Progression and Flavonoid Metabolism in
      Grape Berries Grown under Double Cropping System.
AB  - A double cropping system has been commercially adopted in southern China, where
      there is abundant sunshine and heat resources. In this viticulture system, the
      first growing season normally starts as a summer cropping cycle; then, the vine
      is pruned and forced, resulting in a second crop in winter. Due to climate
      differences between the summer and winter growing seasons, grape ripening
      progression and flavonoid metabolism vary greatly. Here, the metabolites and
      transcriptome of flavonoid pathways were analyzed in grapes grown under two
      growing seasons at different stages. Notably, the winter cropping cycle strongly
      increased flavonoid levels by several times in comparison to summer grapes, while
      the summer season took a major toll on anthocyanin and flavonol accumulation,
      since the winter cropping greatly triggered the expression of upstream genes in
      the flavonoid pathway in a coordinated expression pattern. Moreover, the ratio of
      VviF3'5'Hs (flavonoid 3'5'-hydroxylase) to VviF3'Hs (flavonoid 3'-hydroxylase)
      transcript levels correlated remarkably well with the ratio of 3'5'-substituted
      to 3'-substituted flavonoids, which was presumed to control the flux of
      intermediates into different flavonoid branches. On the other hand, the
      phenological phase also varied greatly in the two crops. Compared to summer
      cropping, winter growing season accelerated the duration from budburst to
      veraison, therefore advancing the onset of ripening, but also prolonging the
      duration of ripening progression due to the purposes to harvest high-quality
      grapes. The differential expression pattern of hormone-related genes between the
      two cropping cycles might explain this phenomenon.

PMID- 29176989
TI  - Culm Age and Rhizome Affects Night-Time Water Recharge in the Bamboo
      Phyllostachys pubescens.
AB  - Bamboo species-the only herbaceous trees-have unique structural and physiological
      characteristics that differ from those of other tree taxa. However, the role of
      night-time water use in bamboo is poorly understood and has rarely been
      investigated. We studied the day- and night-time sap flow response to culm age
      and rhizome structure in three age levels (juvenile, mature, and senescent) of
      Phyllostachys pubescens growing in the Nankun Mountain Natural Reserve, South
      China. We found that sap flow density and whole-tree hydraulic conductance
      decreased with culm age. After cutting of rhizome, the day-time sap flow and
      night-time water recharge decreased obviously. In addition, night-time water
      recharge accounted for the largest proportion (up to 30%) of total daily
      transpiration in normal senescent bamboos. Therefore, our study indicates that
      the connected rhizome system and night-time water recharge played a significant
      role in water compensation during the day and at night in bamboos. Night-time
      water recharge is especially critical to senescent bamboos, given their weaker
      transpiration due to the lower whole-tree hydraulic conductance, and
      consequently, they are more dependent on night-time water recharge for fulfilling
      their whole-day water consumption needs.

PMID- 29176988
TI  - Genome-Wide Association Mapping of Flowering and Ripening Periods in Apple.
AB  - Deciphering the genetic control of flowering and ripening periods in apple is
      essential for breeding cultivars adapted to their growing environments. We
      implemented a large Genome-Wide Association Study (GWAS) at the European level
      using an association panel of 1,168 different apple genotypes distributed over
      six locations and phenotyped for these phenological traits. The panel was
      genotyped at a high-density of SNPs using the Axiom(r)Apple 480 K SNP array. We
      ran GWAS with a multi-locus mixed model (MLMM), which handles the putatively
      confounding effect of significant SNPs elsewhere on the genome. Genomic regions
      were further investigated to reveal candidate genes responsible for the
      phenotypic variation. At the whole population level, GWAS retained two SNPs as
      cofactors on chromosome 9 for flowering period, and six for ripening period (four
      on chromosome 3, one on chromosome 10 and one on chromosome 16) which, together
      accounted for 8.9 and 17.2% of the phenotypic variance, respectively. For both
      traits, SNPs in weak linkage disequilibrium were detected nearby, thus suggesting
      the existence of allelic heterogeneity. The geographic origins and relationships
      of apple cultivars accounted for large parts of the phenotypic variation.
      Variation in genotypic frequency of the SNPs associated with the two traits was
      connected to the geographic origin of the genotypes (grouped as North+East, West
      and South Europe), and indicated differential selection in different growing
      environments. Genes encoding transcription factors containing either NAC or MADS
      domains were identified as major candidates within the small confidence intervals
      computed for the associated genomic regions. A strong microsynteny between apple
      and peach was revealed in all the four confidence interval regions. This study
      shows how association genetics can unravel the genetic control of important
      horticultural traits in apple, as well as reduce the confidence intervals of the
      associated regions identified by linkage mapping approaches. Our findings can be
      used for the improvement of apple through marker-assisted breeding strategies
      that take advantage of the accumulating additive effects of the identified SNPs.

PMID- 29176990
TI  - Uranium Leaching from Contaminated Soil Utilizing Rhamnolipid, EDTA, and Citric
      Acid.
AB  - Biosurfactants have recently gained attention as "green" agents that can be used
      to enhance the remediation of heavy metals and some organic matter in
      contaminated soils. The overall objective of this paper was to investigate
      rhamnolipid, a microbial produced biosurfactant, and its ability to leach uranium
      present in contaminated soil from an abandoned mine site. Soil samples were
      collected from two locations in northern Arizona: Cameron (site of open pit
      mining) and Leupp (control-no mining). The approach taken was to first determine
      the total uranium content in each soil using a hydrofluoric acid digestion, then
      comparing the amount of metal removed by rhamnolipid to other chelating agents
      EDTA and citric acid, and finally determining the amount of soluble metal in the
      soil matrix using a sequential extraction. Results suggested a complex system for
      metal removal from soil utilizing rhamnolipid. It was determined that rhamnolipid
      at a concentration of 150 MUM was as effective as EDTA but not as effective as
      citric acid for the removal of soluble uranium. However, the rhamnolipid was only
      slightly better at removing uranium from the mining soil compared to a purified
      water control. Overall, this study demonstrated that rhamnolipid ability to
      remove uranium from contaminated soil is comparable to EDTA and to a lesser
      extent citric acid, but, for the soils investigated, it is not significantly
      better than a simple water wash.

PMID- 29176992
TI  - Immunosenescence in persons with spinal cord injury in relation to urinary tract
      infections -a cross-sectional study.
AB  - Background: Individuals with a spinal cord injury (SCI), despite specialized
      rehabilitation and good health care, have a reduced life expectancy. Infectious
      diseases, such as pneumonias, infected pressure sores and urinary tract
      infections (UTI) have been identified as the leading causes of mortality. We
      hypothesise that a premature onset of immune frailty occurs in SCI, possibly
      caused also by recurrent urinary tract infections.A cross sectional study was
      performed comparing blood and urine samples between able bodied controls (n = 84)
      and persons with spinal cord injury (n = 85). The results were grouped according
      to age (below and above 60 years). Assessed were the abundancies of immune cells,
      the concentration of soluble biomarkers, the in vitro functioning of lymphocytes
      as well as phenotypic exhaustion of T-cells in blood and urine. Further, the
      leucocyte telomere length and the cytomegalovirus (CMV) serological status were
      compared between the groups. Results: We observed in people with SCI lower
      proportions of naive T-cells, more memory T-cells, reduced T-cell proliferation
      and higher CMV prevalence compared to age-matched controls. SCI participants
      older than 60 years had a higher prevalence of UTI compared with SCI persons
      younger than 60 years. Conclusion: The immune system of people with SCI shows
      traits of an increased immunological strain and a premature onset of immune
      frailty. The role of UTI in the onset of immune frailty remains to be elucidated
      as we did not see significantly higher abundancies of circulating UTI-bacteria
      specific T-cell clones in persons with SCI. We assume that any impact of UTI on
      the immune system might be compartmentalized and locally restricted to the
      urinary tract.

PMID- 29176991
TI  - Asthma biomarkers in the age of biologics.
AB  - The heterogeneous nature of asthma has been understood for decades, but the
      precise categorization of asthma has taken on new clinical importance in the era
      of specific biologic therapy. The simple categories of allergic and non-allergic
      asthma have given way to more precise phenotypes that hint at underlying biologic
      mechanisms of variable airflow limitation and airways inflammation. Understanding
      these mechanisms is of particular importance for the approximately 10% of
      patients with severe asthma. Biomarkers that aid in phenotyping allow physicians
      to "personalize" treatment with targeted biologic agents. Unfortunately, testing
      for these biomarkers is not routine in patients whose asthma is refractory to
      standard therapy. Scientific advances in the recognition of sensitive and
      specific biomarkers are steadily outpacing the clinical availability of reliable
      and non-invasive assessment methods designed for the prompt and specific
      diagnosis, classification, treatment, and monitoring of severe asthma patients.
      This article provides a practical overview of current biomarkers and testing
      methods for prompt, effective management of patients with severe asthma that is
      refractory to standard therapy.

PMID- 29176993
TI  - An excess dietary vitamin E concentration does not influence Nrf2 signaling in
      the liver of rats fed either soybean oil or salmon oil.
AB  - Background: Reactive oxygen species (ROS) are known to stimulate the activation
      of nuclear factor-erythroid 2-related factor-2 (Nrf2), the key regulator of the
      antioxidant and cytoprotective defense system in the body. The hypothesis
      underlying this study was that high dietary concentrations of vitamin E suppress
      Nrf2 activation, and thus could weaken the body's antioxidative and
      cytoprotective capacity. As the effect of vitamin E on Nrf2 pathway might be
      influenced by concentrations of fatty acids susceptible to oxidation in the diet,
      we used also diets containing either soybean oil as a reference oil or salmon oil
      as a source of oil rich in n-3 polyunsatuated fatty acids. Methods: Seventy-two
      rats were divided into 6 groups of rats which received diets with either 25, 250
      or 2500 mg vitamin E/kg, with either soybean oil or salmon oil as dietary fat
      sources according to a bi-factorial experimental design. Electron spin resonance
      spectroscopy was used to determine ROS production in the liver. qPCR analysis and
      western blot were performed to examine the expression of Nrf2 target genes in the
      liver of rats. Results: Rats fed the salmon oil diet with 25 mg vitamin E/kg
      showed a higher production of ROS in the liver than the 5 other groups of rats
      which did not differ in ROS production. Relative mRNA concentrations of NFE2L2
      (encoding Nrf2), KEAP1 and various Nrf2 target genes, protein concentrations of
      glutathione peroxidase (GPX), heme oxygenase 1 (HO-1), NAD(P)H quinone
      dehydrogenase 1 (NQO1) and activities of the antioxidant enzymes GPX, superoxide
      dismutase and catalase were not influenced by the dietary vitamin E
      concentration. The dietary fat had also less effect on Nrf2 target genes and no
      effect on protein concentrations of GPX, HO-1, NQO1 and activities of antioxidant
      enzymes. Dietary vitamin E concentration and type of fat moreover had less effect
      on mRNA concentrations of genes and concentrations of proteins involved in the
      unfolded protein response, a pathway which is closely linked with activation of
      Nrf2. Conclusion: We conclude that excess dietary concentrations of vitamin E do
      not suppress Nrf2 signaling, and thus do not weaken the endogenous antioxidant
      and cytoprotective capacity in the liver of rats.

PMID- 29176994
TI  - Antiobesity potential of Piperonal: promising modulation of body composition,
      lipid profiles and obesogenic marker expression in HFD-induced obese rats.
AB  - Background: Black pepper or Piper nigrum is a well-known spice, rich in a variety
      of bioactive compounds, and widely used in many cuisines across the world. In the
      Indian traditional systems of medicine, it is used to treat gastric and
      respiratory ailments. The purpose of this investigation is to study the
      antihyperlipidemic and antiobesity effects of piperonal in high-fat diet (HFD)
      induced obese rats. Methods: Piperonal, an active constituent of Piper nigrum
      seeds, was isolated and confirmed by HPLC, 1H and 13C NMR spectroscopy. Male SD
      rats were fed on HFD for 22 weeks; Piperonal was supplemented from the 16th week
      as mentioned in the experimental design. Changes in body weight and body
      composition were measured by TOBEC, bone mineral composition and density were
      measured by DXA, and adipose tissue distribution was measured by 7 T-MRI. Plasma
      levels of glucose, insulin, insulin resistance and lipid profiles of plasma,
      liver and kidney, adipocyte hormones and liver antioxidants were evaluated using
      standard kit methods. Expression levels of adipogenic and lipogenic genes, such
      as PPAR-gamma, FAS, Fab-4, UCP-2, SREBP-1c, ACC, HMG-COA and TNF-alpha were
      measured by RT-PCR. Histopathological examination of adipose and liver tissues
      was also carried out in experimental rats. Results: HFD substantially induced
      body weight, fat%, adipocyte size, circulatory and tissue lipid profiles. It
      elevated the plasma levels of insulin, insulin resistance and leptin but
      decreased the levels of adiponectin, BMC and BMD. Increased expression of PPAR
      gamma, FAS, Fab-4, UCP-2, SREBP-1c, ACC, and TNF-alpha was noticed in HFD-fed
      rats. However, supplementation of piperonal (20, 30 and 40 mg/kg b.wt) for 42
      days considerably and dose-dependently attenuated the HFD-induced alterations,
      with the maximum therapeutic activity being noticed at 40 mg/kg b.wt.
      Conclusions: Piperonal significantly attenuated HFD-induced body weight and
      biochemical changes through modulation of key lipid metabolizing and obesogenic
      genes. Our findings demonstrate the efficacy of piperonal as a potent antiobesity
      agent, provide scientific evidence for its traditional use and suggest the
      possible mechanism of action.

PMID- 29176995
TI  - Depression is related to dietary diversity score in women: a cross-sectional
      study from a developing country.
AB  - Background: Substantial evidence provides support for the role of diet in the
      prevention and control of mental disorders. However, since there is no study
      regarding the relationship between dietary diversity and stress or depression, we
      aimed to determine the relationship between the dietary diversity score (DDS) and
      stress and depression in women. Methods: This descriptive-analytical cross
      sectional study was performed on 360 women aged 20-49 years attending health
      centers in the south of Tehran. The dietary intake and score of depression,
      anxiety, and stress were measured using a 24-h dietary recall and the 42-item
      depression, anxiety, stress scales questionnaire, respectively. The DDS was
      calculated based on the FAO 2013 guidelines. Data were analyzed using Chi-square,
      analysis of variance, Spearman correlation coefficient, and multivariable
      logistic regression tests. Results: In total, 31.4 and 25.8% of the subjects
      suffered from depression and stress, respectively. After adjusting for
      confounders, a one-unit increase in DDS was associated with a 39% reduction in
      the risk of severe depression. The DDS was not significantly associated with mild
      or moderate depression, and no significant relationship was observed between the
      DDS and stress. Conclusions: The DDS could be inversely associated with
      depression in women. Since we observed no significant relationship between stress
      and DDS, further studies are needed in this regard.

PMID- 29176996
TI  - Mental, neurologic, and substance use (MNS) disorders among street homeless
      people in Ethiopia.
AB  - Background: About 25-60% of the homeless population is reported to have some form
      of mental disorder. To our knowledge, there are no studies aimed at the
      screening, diagnosis, treatment, care, rehabilitation, and support of homeless
      people with mental, neurologic, and substance use (MNS) disorders in general in
      Ethiopia. This is the first study of its kind in Africa which was aimed at
      screening, diagnosis, care, treatment, rehabilitation, and support of homeless
      individuals with possible MNS disorder. Methods: Community-based survey was
      conducted from January to March 2015. Homeless people who had overt and
      observable psychopathology and positive for screening instruments (SRQ20, ASSIST,
      and PSQ) were involved in the survey and further assessed for possible diagnosis
      by structured clinical interview for DSM-IV diagnoses and international
      diagnostic criteria for seizure disorders for possible involvement in care,
      treatment, rehabilitation services, support, and training. The Statistical
      Program for Social Science (SPSS version 20) was used for data entry, clearance,
      and analyses. Results: A total of 456 homeless people were involved in the
      survey. Majority of the participants were male (n = 402; 88.16%). Most of the
      homeless participants had migrated into Addis Ababa from elsewhere in Ethiopia
      and Eritrea (62.50%). Mental, neurologic, and substance use disorders resulted to
      be common problems in the study participants (92.11%; n = 420). Most of the
      participants with mental, neurologic, and substance use disorders (85.29%; n =
      354) had psychotic disorders. Most of those with psychosis had schizophrenia
      (77.40%; n = 274). Almost all of the participants had a history of substance use
      (93.20%; n = 425) and about one in ten individuals had substance use disorders
      (10.54%; n = 48). Most of the participants with substance use disorder had
      comorbid other mental and neurologic disorders (83.33%; n = 40). Conclusion and
      recommendation: Mental, neurologic, and substance use disorders are common
      (92.11%) among street homeless people in Ethiopia. The development of centers for
      care, treatment, rehabilitation, and support of homeless people with mental,
      neurologic, and substance use disorders is warranted. In addition, it is
      necessary to improve the accessibility of mental health services and promote
      better integration between mental and primary health care services, as a means to
      offer a better general care and to possibly prevent homelessness among mentally
      ill.

PMID- 29176997
TI  - Association between an angiotensin-converting enzyme gene polymorphism and
      Alzheimer's disease in a Tunisian population.
AB  - Background: The angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D
      or indel) polymorphism has long been linked to Alzheimer's disease (AD), but the
      interpretation of established data remains controversial. The aim of this study
      was to determine whether the angiotensin-converting enzyme is associated with the
      risk of Alzheimer's disease in Tunisian patients. Methods: We analyzed the
      genotype and allele frequency distribution of the ACE I/D gene polymorphism in 60
      Tunisian AD patients and 120 healthy controls. Results: There is a significantly
      increased risk of AD in carriers of the D/D genotype (51.67% in patients vs.
      31.67% in controls; p = .008, OR = 2.32). The D allele was also more frequently
      found in patients compared with controls (71.67% vs. 56.25%; p = .003, OR = 2.0).
      Moreover, as assessed by the Mini-Mental State Examination, patient D/D carriers
      were more frequently found to score in the severe category of dementia (65%) as
      compared to the moderate category (32%) or mild category (3%). Conclusions: The
      D/D genotype and D allele of the ACE I/D polymorphism were associated with an
      increased risk in the development of AD in a Tunisian population. Furthermore, at
      the time of patient evaluation (average age 75 years), patients suffering with
      severe dementia were found predominantly in D/D carriers and, conversely, the D/D
      genotype and D allele were more frequently found in AD patients with severe
      dementia. These preliminary exploratory results should be confirmed in larger
      studies and further work is required to explore and interpret possible
      alternative findings in diverse populations.

PMID- 29176998
TI  - A novel 3D imaging system for strawberry phenotyping.
AB  - Background: Accurate and quantitative phenotypic data in plant breeding
      programmes is vital in breeding to assess the performance of genotypes and to
      make selections. Traditional strawberry phenotyping relies on the human eye to
      assess most external fruit quality attributes, which is time-consuming and
      subjective. 3D imaging is a promising high-throughput technique that allows
      multiple external fruit quality attributes to be measured simultaneously.
      Results: A low cost multi-view stereo (MVS) imaging system was developed, which
      captured data from 360 degrees  around a target strawberry fruit. A 3D point
      cloud of the sample was derived and analysed with custom-developed software to
      estimate berry height, length, width, volume, calyx size, colour and achene
      number. Analysis of these traits in 100 fruits showed good concordance with
      manual assessment methods. Conclusion: This study demonstrates the feasibility of
      an MVS based 3D imaging system for the rapid and quantitative phenotyping of
      seven agronomically important external strawberry traits. With further
      improvement, this method could be applied in strawberry breeding programmes as a
      cost effective phenotyping technique.

PMID- 29176999
TI  - A robot-assisted imaging pipeline for tracking the growths of maize ear and silks
      in a high-throughput phenotyping platform.
AB  - Background: In maize, silks are hundreds of filaments that simultaneously emerge
      from the ear for collecting pollen over a period of 1-7 days, which largely
      determines grain number especially under water deficit. Silk growth is a major
      trait for drought tolerance in maize, but its phenotyping is difficult at
      throughputs needed for genetic analyses. Results: We have developed a
      reproducible pipeline that follows ear and silk growths every day for hundreds of
      plants, based on an ear detection algorithm that drives a robotized camera for
      obtaining detailed images of ears and silks. We first select, among 12 whole
      plant side views, those best suited for detecting ear position. Images are
      segmented, the stem pixels are labelled and the ear position is identified based
      on changes in width along the stem. A mobile camera is then automatically
      positioned in real time at 30 cm from the ear, for a detailed picture in which
      silks are identified based on texture and colour. This allows analysis of the
      time course of ear and silk growths of thousands of plants. The pipeline was
      tested on a panel of 60 maize hybrids in the PHENOARCH phenotyping platform. Over
      360 plants, ear position was correctly estimated in 86% of cases, before it could
      be visually assessed. Silk growth rate, estimated on all plants, decreased with
      time consistent with literature. The pipeline allowed clear identification of the
      effects of genotypes and water deficit on the rate and duration of silk growth.
      Conclusions: The pipeline presented here, which combines computer vision, machine
      learning and robotics, provides a powerful tool for large-scale genetic analyses
      of the control of reproductive growth to changes in environmental conditions in a
      non-invasive and automatized way. It is available as Open Source software in the
      OpenAlea platform.

PMID- 29177000
TI  - Correction to: The Tree Drought Emission MONitor (Tree DEMON), an innovative
      system for assessing biogenic volatile organic compounds emission from plants.
AB  - [This corrects the article DOI: 10.1186/s13007-017-0166-6.].

PMID- 29177001
TI  - A cautionary note on the use of chromosome conformation capture in plants.
AB  - Background: The chromosome conformation capture (3C) technique is a method to
      study chromatin interactions at specific genomic loci. Initially established for
      yeast the 3C technique has been adapted to plants in recent years in order to
      study chromatin interactions and their role in transcriptional gene regulation.
      As the plant scientific community continues to implement this technology, a
      discussion on critical controls, validations steps and interpretation of 3C data
      is essential to fully benefit from 3C in plants. Results: Here we assess the
      reliability and robustness of the 3C technique for the detection of chromatin
      interactions in Arabidopsis. As a case study, we applied this methodology to the
      genomic locus of a floral integrator gene SUPPRESSOR OF OVEREXPRESSION OF
      CONSTANS1 (SOC1), and demonstrate the need of several controls and standard
      validation steps to allow a meaningful interpretation of 3C data. The intricacies
      of this promising but challenging technique are discussed in depth. Conclusions:
      The 3C technique offers an interesting opportunity to study chromatin
      interactions at a resolution infeasible by microscopy. However, for
      interpretation of 3C interaction data and identification of true interactions, 3C
      technology demands a stringent experimental setup and extreme caution.

PMID- 29177002
TI  - Non-invasive imaging of plant roots in different soils using magnetic resonance
      imaging (MRI).
AB  - Background: Root systems are highly plastic and adapt according to their soil
      environment. Studying the particular influence of soils on root development
      necessitates the adaptation and evaluation of imaging methods for multiple
      substrates. Non-invasive 3D root images in soil can be obtained using magnetic
      resonance imaging (MRI). Not all substrates, however, are suitable for MRI. Using
      barley as a model plant we investigated the achievable image quality and the
      suitability for root phenotyping of six commercially available natural soil
      substrates of commonly occurring soil textures. The results are compared with two
      artificially composed substrates previously documented for MRI root imaging.
      Results: In five out of the eight tested substrates, barley lateral roots with
      diameters below 300 um could still be resolved. In two other soils, only the
      thicker barley seminal roots were detectable. For these two substrates the
      minimal detectable root diameter was between 400 and 500 um. Only one soil did
      not allow imaging of the roots with MRI. In the artificially composed substrates,
      soil moisture above 70% of the maximal water holding capacity (WHCmax) impeded
      root imaging. For the natural soil substrates, soil moisture had no effect on MRI
      root image quality in the investigated range of 50-80% WHCmax. Conclusions:
      Almost all tested natural soil substrates allowed for root imaging using MRI.
      Half of these substrates resulted in root images comparable to our current lab
      standard substrate, allowing root detection down to a diameter of 300 um. These
      soils were used as supplied by the vendor and, in particular, removal of
      ferromagnetic particles was not necessary. With the characterization of different
      soils, investigations such as trait stability across substrates are now possible
      using noninvasive MRI.

PMID- 29177003
TI  - Corrigendum to "Comparative Sensitivity Analysis of Muscle Activation Dynamics".
AB  - [This corrects the article DOI: 10.1155/2015/585409.].

PMID- 29177004
TI  - Active fraction (HS7) from Taiwanofungus camphoratus inhibits AKT-mTOR, ERK and
      STAT3 pathways and induces CDK inhibitors in CL1-0 human lung cancer cells.
AB  - Background: The non-small cell lung cancer (NSCLC) is the leading cause of cancer
      death worldwide. In NSCLC, the oncogenic AKT-mTOR, ERK and STAT3 pathways are
      commonly dysregulated and have emerged as attractive targets for therapeutic
      developments. In a relatively limited subset of NSCLC, these pathways driven by
      mutant EGFR can be treated by the tyrosine kinase inhibitors (TKIs)-mediated
      targeted therapy. However, for the most NSCLC, more novel targeted agents are
      imperatively needed. Therefore, we investigated the inhibitory effects of the
      active fraction HS7 from Taiwanofungus camphoratus, a unique medicinal fungus in
      Taiwan, on these pathways in CL1-0 EGFR wild-type human NSCLC cells. Methods: The
      active fraction HS7 was prepared by n-hexane extraction of T. camphoratus
      followed by silica gel chromatography. Its effects on the cell viabilities were
      determined by sulforhodamine B colorimetric assay. Flow cytometry was used to
      analyze cell-cycle regulation and apoptosis induction. The changes in cellular
      protein levels were examined by Western blot. Results: The active fraction HS7
      vigorously inhibits AKT-mTOR, ERK and STAT3 signaling pathways in CL1-0 cells. At
      dose of 25 MUg/mL, these signaling pathways were almost completely inhibited by
      HS7, accompanied with induction of cyclin-dependent kinase inhibitors such as
      p15, p21 and p27. Accordingly, the AKT-mTOR downstream targets p-p70S6K and HIF
      1alpha were also suppressed as well. At this dose, the cell proliferation was
      profoundly suppressed to 23.4% of control and apoptosis induction was observed.
      Conclusions: The active fraction HS7 from n-hexane extract of T. camphoratus
      exerts multi-targeting activity on the suppression of AKT-mTOR, ERK and STAT3
      pathways and induction of p15, p21 and p27 in EGFR wild-type NSCLC cells. This
      multi-targeting activity of HS7 suggests its potential as an alternative medicine
      for the treatment of EGFR TKIs resistant NSCLC.

PMID- 29177005
TI  - Altered Pre-Ejection Period Response to Social Evaluative Threat in Adolescents
      with Autism Spectrum Disorder.
AB  - Introduction: The autonomic nervous system (ANS) is involved in regulating social
      behavior; Autism Spectrum Disorder (ASD) is characterized by alterations in
      social behavior and reduced physiological response to threat. We hypothesized
      that adolescents with ASD would show reduced ANS response to social threat.
      Methods: Eighteen males with ASD and thirteen males with typical development
      (TD), ages 12 to 17, completed a social threat paradigm while wearing an
      impedance cardiography apparatus. We calculated pre-ejection period (PEP) and
      tested for between-group differences in PEP response to social threat. We also
      conducted correlation analyses between PEP change scores and clinical symptom
      scales. Results: There was an effect of diagnosis on change in PEP from baseline
      to the onset of social threat (F=7.60, p=0.01), with greater changes in PEP in TD
      compared to ASD. PEP change score and the Social Communication Questionnaire
      (r=0.634, p=0.005) and the ADHD Problems Subscale of the Child Behavior Checklist
      (r=0.568, p=0.014) were correlated. Conclusions: These findings suggest reduced
      arousal in response to social threat in ASD, with preliminary evidence that
      reduced sympathetic activation is associated with increased social behavior
      symptoms.

PMID- 29177007
TI  - A simplified microwave-based motion detector for home cage activity monitoring in
      mice.
AB  - Background: Locomotor activity of rodents is an important readout to assess well
      being and physical health, and is pivotal for behavioral phenotyping. Measuring
      homecage-activity with standard and cost-effective optical methods in mice has
      become difficult, as modern housing conditions (e.g. individually ventilated
      cages, cage enrichment) do not allow constant, unobstructed, visual access.
      Resolving this issue either makes greater investments necessary, especially if
      several experiments will be run in parallel, or is at the animals' expense. The
      purpose of this study is to provide an easy, yet satisfying solution for the
      behavioral biologist at novice makers level. Results: We show the design,
      construction and validation of a simplified, low-cost, radar-based motion
      detector for home cage activity monitoring in mice. In addition we demonstrate
      that mice which have been selectively bred for low levels of anxiety-related
      behavior (LAB) have deficits in circadian photoentrainment compared to CD1
      control animals. Conclusion: In this study we have demonstrated that our proposed
      low-cost microwave-based motion detector is well-suited for the study of
      circadian rhythms in mice.

PMID- 29177006
TI  - Tissue specific microenvironments: a key tool for tissue engineering and
      regenerative medicine.
AB  - The accumulated evidence points to the microenvironment as the primary mediator
      of cellular fate determination. Comprised of parenchymal cells, stromal cells,
      structural extracellular matrix proteins, and signaling molecules, the
      microenvironment is a complex and synergistic edifice that varies tissue to
      tissue. Furthermore, it has become increasingly clear that the microenvironment
      plays crucial roles in the establishment and progression of diseases such as
      cardiovascular disease, neurodegeneration, cancer, and ageing. Here we review the
      historical perspectives on the microenvironment, and how it has directed current
      explorations in tissue engineering. By thoroughly understanding the role of the
      microenvironment, we can begin to correctly manipulate it to prevent and cure
      diseases through regenerative medicine techniques.

PMID- 29177008
TI  - Deciphering cyanobacterial phenotypes for fast photoautotrophic growth via
      isotopically nonstationary metabolic flux analysis.
AB  - Background: Synechococcus elongatus UTEX 2973 is the fastest growing
      cyanobacterium characterized to date. Its genome was found to be 99.8% identical
      to S. elongatus 7942 yet it grows twice as fast. Current genome-to-phenome
      mapping is still poorly performed for non-model organisms. Even for species with
      identical genomes, cell phenotypes can be strikingly different. To understand
      Synechococcus 2973's fast-growth phenotype and its metabolic features
      advantageous to photo-biorefineries, 13C isotopically nonstationary metabolic
      flux analysis (INST-MFA), biomass compositional analysis, gene knockouts, and
      metabolite profiling were performed on both strains under various growth
      conditions. Results: The Synechococcus 2973 flux maps show substantial carbon
      flow through the Calvin cycle, glycolysis, photorespiration and pyruvate kinase,
      but minimal flux through the malic enzyme and oxidative pentose phosphate
      pathways under high light/CO2 conditions. During fast growth, its pool sizes of
      key metabolites in central pathways were lower than suboptimal growth.
      Synechococcus 2973 demonstrated similar flux ratios to Synechococcus 7942 (under
      fast growth conditions), but exhibited greater carbon assimilation, higher NADPH
      concentrations, higher energy charge (relative ATP ratio over ADP and AMP), less
      accumulation of glycogen, and potentially metabolite channeling. Furthermore,
      Synechococcus 2973 has very limited flux through the TCA pathway with small pool
      sizes of acetyl-CoA/TCA intermediates under all growth conditions. Conclusions:
      This study employed flux analysis to investigate phenotypic heterogeneity among
      two cyanobacterial strains with near-identical genome background. The
      flux/metabolite profiling, biomass composition analysis, and genetic modification
      results elucidate a highly effective metabolic topology for CO2 assimilatory and
      biosynthesis in Synechococcus 2973. Comparisons across multiple Synechococcus
      strains indicate faster metabolism is also driven by proportional increases in
      both photosynthesis and key central pathway fluxes. Moreover, the flux
      distribution in Synechococcus 2973 supports the use of its strong sugar phosphate
      pathways for optimal bio-productions. The integrated methodologies in this study
      can be applied for characterizing non-model microbial metabolism.

PMID- 29177009
TI  - Label-free, simultaneous quantification of starch, protein and triacylglycerol in
      single microalgal cells.
AB  - Background: Current approaches for quantification of major energy-storage forms
      in microalgae, including starch, protein and lipids, generally require cell
      cultivation to collect biomass followed by tedious and time-consuming analytical
      procedures. Thus, label-free, non-destructive and simultaneous quantification of
      such macromolecules at single-cell resolution is highly desirable in microalgal
      feedstock development and bioprocess control. Results: Here, we established a
      method based on single-cell Raman spectra (SCRS) that simultaneously quantifies
      the contents of starch, protein, triacylglycerol (TAG) and lipid unsaturation
      degree in individual Chlamydomonas reinhardtii cells. Measurement accuracy for
      the contents based on full SCRS spectrum each reached 96.86-99.24%, all
      significantly higher than single peak-based models. However, accuracy and
      reliability of measurement are dependent on the number of cells sampled, thus a
      formal mathematical framework was proposed and validated to rationally define
      "minimal sampling depth" for a given state of cellular population. Furthermore, a
      barcode consisting of 13 marker Raman peaks was proposed to characterize the
      temporal dynamics of these energy-storage products, which revealed that the
      average contents of starch and TAG increased, while their heterogeneity indices
      decreased, with those of protein being exactly the opposite. Finally, our method
      is widely applicable, as measurements among cells from liquid suspension culture,
      wet paste and frozen dried powder all exhibited excellent consistency.
      Conclusions: When sampled at proper depth, SCRS can serve as a quantitative and
      generally applicable tool for characterization and screening of strains and
      bioprocesses based on the profile of energy-storage macromolecules and their
      among-cell heterogeneity.

PMID- 29177010
TI  - 7p15 deletion as the cause of hand-foot-genital syndrome: a case report,
      literature review and proposal of a minimum region for this phenotype.
AB  - Background: Hand-foot-genital syndrome (HFGS) is a rare condition characterized
      by congenital malformations in the limbs and genitourinary tract. Generally, this
      syndrome occurs due to point mutations that cause loss of function of the HOXA13
      gene, which is located on 7p15; however, there are some patients with HFGS caused
      by interstitial deletions in this region. Case presentation: We describe a
      pediatric Mexican patient who came to the Medical Genetics Department at the
      National Institute of Pediatrics because he presented with genital, hand and feet
      anomalies, facial dysmorphisms, and learning difficulties. Array CGH reported a
      12.7 Mb deletion that includes HOXA13. Conclusions: We compared our patient with
      cases of HFGS reported in the literature caused by a microdeletion; we found a
      minimum shared region in 7p15.2. By analyzing the phenotype in these patients, we
      suggest that microdeletions in this region should be investigated in all patients
      with clinical characteristics of HFGS who also present with dysplastic ears,
      mainly low-set implantation with a prominent antihelix, as well as a low nasal
      bridge and long philtrum.

PMID- 29177011
TI  - X-derived marker chromosome in patient with mosaic Turner syndrome and Dandy
      Walker syndrome: a case report.
AB  - Background: Small supernumerary marker chromosomes can be derived from autosomes
      and sex chromosomes and can accompany chromosome pathologies, such as Turner
      syndrome. Case presentation: Here, we present a case report of a patient with
      mosaic Turner syndrome and Dandy-Walker syndrome carrying a marker chromosome. We
      showed the presence of the marker chromosome in 33.8% of blood cells. FISH of the
      probe derived from the marker chromosome by microdissection revealed that it
      originated from the centromeric region of chromosome X. Additionally, we showed
      no telomeric sequences and no XIST sequence in the marker chromosome. This is the
      first report of these two syndromes accompanied by the presence of a marker
      chromosome. Conclusion: Marker chromosome was X-derived and originated from
      centromeric region. Patient has mild symptoms but there is no XIST gene in marker
      chromosome. Trial registration: CPG137. Registered 03 March 2017.

PMID- 29177012
TI  - CRISPR-like sequences in Helicobacter pylori and application in genotyping.
AB  - Background: Many bacteria and archaea possess a defense system called clustered
      regularly interspaced short palindromic repeats (CRISPR) associated proteins
      (CRISPR-Cas system) against invaders such as phages or plasmids. This system has
      not been demonstrated in Helicobacter pylori. The numbers of spacer in CRISPR
      array differ among bacterial strains and can be used as a genetic marker for
      bacterial typing. Results: A total of 36 H. pylori isolates were collected from
      patients in three hospitals located in the central (PBH) and southern (SKH)
      regions of Thailand. It is of interest that CRISPR-like sequences of this
      bacterium were detected in vlpC encoded for VacA-like protein C. Virulence genes
      were investigated and the most pathogenic genotype (cagA vacA s1m1) was detected
      in 17 out of 29 (58.6%) isolates from PBH and 5 out of 7 (71.4%) from SKH. vapD
      gene was identified in each one isolate from PBH and SKH. CRISPR-like sequences
      and virulence genes of 20 isolates of H. pylori obtained in this study were
      analyzed and CRISPR-virulence typing was constructed and compared to profiles
      obtained by the random amplification of polymorphic DNA (RAPD) technique. The
      discriminatory power (DI) of CRISPR-virulence typing was not different from RAPD
      typing. Conclusion: CRISPR-virulence typing in H. pylori is easy and reliable for
      epidemiology and can be used for inter-laboratory interpretation.

PMID- 29177014
TI  - Proctors in interventional cardiology: go beyond mentoring and monitoring!

PMID- 29177013
TI  - Vitamin D is associated with metabotropic but not neurotrophic effects of
      exercise in ovariectomized rats.
AB  - Purpose: Here, we studied the beneficial effects of aerobic exercise on metabolic
      syndrome components, cognitive performance, brain derived neurotrophic factor
      (BDNF) and irisin in ovariectomized rats with different serum vitamin D (Vit D)
      status. Methods: Eighty female wistar rats were divided into 2 groups of sham
      operated (sham, n = 8), and ovariectomized (OVX, n = 72). Then OVX were divided
      into 9 groups of receiving combination of exercise protocol with low dose of Vit
      D (OVX + EXE + LD), high dose of Vit D (OVX + EXE + HD), Vit D deficiency (OVX +
      EXE - D), and (OVX + EXE + Veh). Also non exercised groups of OVX receiving high
      dose of Vit D (OVX + HD), low dose of Vit D (OVX + LD), Vit D deficiency (OVX -
      D), and Veh (OVX + Veh) were included. After 2 months of related interventions,
      spatial memory was assessed using Morris water maze (MWM), and then metabolic
      syndrome components were measured. Results: High dose of Vit D supplementation
      showed significant reduction in weight (p = 0.001), lipid profiles (p = 0.001),
      visceral fat (p = 0.001) and waist circumference (p = 0.001) regardless of
      exercising or not, with no change in cognitiive function. Serum BDNF level was
      significantly higher in Vit D deficient group (p = 0.001), and was decreased in
      the OVX + HD. In contrary, irisin did not show any significant relationship with
      serum concentration of Vit D, while it was significantly elevated in the
      exercised groups compared with non-exercised counterparts. Conclusion: Vit D
      insufficiency deteriorates metabolic syndrome components, and elevates serum BDNF
      as a compensatory metabotropic factor, and further supplementation significantly
      attenuates these components parallel with reduction in BDNF. In addition, aerobic
      exercise successfully induces various metabolic benefits, provided optimum serum
      level of Vit D.

PMID- 29177016
TI  - 'Caterpillar right ventricle': unusual manifestation of a rare disease.
AB  - : A 66-year-old man presented with abdominal distension and pedal oedema for the
      past 10 years. He had history of right heart failure on several occasions in the
      past, and one of these admissions prompted referral to a cardiac specialist. On
      examination, he had markedly elevated jugular venous pressure with prominent 'y
      descent', a tricuspid regurgitation murmur, gross ascites and pedal oedema. A
      full blood count, routine biochemical screen and serum bicarbonate levels were
      normal. Right ventricular angiogram revealed a 'caterpillar'-like aneurysm of the
      right ventricle (RV) apex (figure 1 arrow) with a dilated right ventricular
      outflow tract and significant tricuspid regurgitation with a dilated right atrium
      (see online supplementary video 1). Figure 1 Acine angiographic frame of the
      right ventricle in posteroanterior view, showing a 'caterpillar'-like right
      ventricle aneurysm (arrow). 10.1136/heartasia-2017-010957.supp3Supplementary file
      3. Question: On the basis of the clinical and right ventriculography features,
      what is the most likely diagnosis for this patient?Arrhythmogenic right
      ventricular cardiomyopathy (ARVC)Right ventricular endomyocardial fibrosis (RV
      EMF) with an RV aneurysmCardiac sarcoidosisCongenital diverticulum of the right
      ventricle.

PMID- 29177015
TI  - Clinical significance of atrial high-rate episodes for thromboembolic events in
      Japanese population.
AB  - Objective: The clinical significance of atrial high-rate episodes (AHREs)
      detected by cardiac devices among patients with implantable pacemakers has
      recently emerged. However, the relationship between AHREs and ischaemic stroke
      and systemic embolism (SE) is not well understood in the Japanese population.
      Methods: This study included 343 patients with pacemakers capable of continuous
      atrial rhythm monitoring (167 males; mean age, 80+/-7 years). Atrial
      tachyarrhythmia detection was programmed to the nominal setting of each device,
      and AHRE was defined as any episode of sustained atrial tachyarrhythmia lasting
      for more than 6 min. Thromboembolic risk was defined based on the CHADS2 score.
      Results: During the follow-up period (52+/-30 months), 165 (48%) patients had at
      least one episode of AHREs, and 19 (6%) patients experienced stroke/SE. Among
      patients who experienced stroke/SE, 14 had AHREs before the stroke/SE. AHREs were
      significantly associated with stroke/SE (HR 2.87; 95% CI 1.10 to 8.90; p=0.03).
      Subgroup analysis conducted to investigate the impact of the CHADS2 score
      severity on stroke/SE revealed that AHREs were not associated with stroke/SE in
      patients with low or intermediate thromboembolic risk (CHADS2 score 0-2; n=217).
      In contrast, among patients with high thromboembolic risk (CHADS2 score>2;
      n=126), there was a significant association between AHREs and the incidence of
      stroke/SE (HR 3.73; 95% CI 1.06 to 13.1; p=0.04). Conclusion: AHREs detected by
      pacemaker were associated with ischaemic stroke/SE in the Japanese population.
      However, this association was observed only in the high thromboembolic risk
      group.

PMID- 29177017
TI  - Iatrogenic radial arteriovenous fistula.

PMID- 29177018
TI  - Study of the association between gait variability and physical activity.
AB  - Background: Gait variability can be considered an indirect measure of gait
      stability, in particular regarding temporal or spatial variability assessment.
      Physical activity, such as walking, is advised for the elderly and can be
      improved by gait stability. The aim of this study was to investigate the
      associations between gait stability and physical activity in women of different
      age ranges. Methods: Forty-two healthy women of different age ranges (18-40 yrs.
      and 65-75 yrs.) were recruited in the study. To assess physical activity, the
      subjects wore a multi-sensor activity monitor for a whole week, inferring the
      time spent in moderate to vigorous physical activity (MVPA). MVPA were analysed
      in bouts of at least 10 subsequent minutes (MVPAbouts) and in overall minutes
      (MVPAtot). A kinematic analysis was performed with an optoelectronic system to
      calculate gait variability - expressed as standard deviation (SD) and coefficient
      of variability (CV) of step width, stride length, stance and swing time (during
      treadmill walking at different speeds). Results: Elderly women, with high walking
      speed (5 km/h), and moderate step width variability (CV = 8-27%), met the
      recommended levels of physical activity (MVPAtot and MVPAbouts). Furthermore,
      gait variability, adjusted for age and number of falls, was significantly and
      negatively associated with MVPAtot only at 3.5 km/h, and with MVPAbouts only at 4
      km/h. Conclusions: In a population of healthy elderly women, gait variability was
      significantly and negatively associated with the level of physical activity.
      Healthy elderly women, with moderate gait variability (step width variability),
      and high preferred walking speed, seem to be able to meet the recommended levels
      of physical activity.

PMID- 29177019
TI  - Ovarian and Breast Cancer Migration Dynamics on Laminin and Fibronectin
      Bidirectional Gradient Fibers Fabricated via Multiphoton Excited Photochemistry.
AB  - Introduction: Migration mis-regulation is a hallmark of cancer, and remains an
      important problem in cancer biology. We postulate the needs for better in vitro
      models to understand the details of cell-matrix interactions. Here, we utilized
      multiphoton excited (MPE) photochemistry to fabricate models to systematically
      study migration dynamics operative in breast and ovarian cancer. Gradients are a
      convenient means to modulate concentration and also have been implicated in
      metastases. Methods: We specifically pattern sub-micron structured gradients from
      laminin and fibronectin whose up-regulation is associated with increased
      metastasis and poor prognosis. We developed a new continuous linear bi
      directional gradient design, permitting exploration of the underlying cell-matrix
      interactions of migration, including speed, directness, and f-actin cytoskeleton
      alignment as a function of concentration. These new models provide both contact
      guidance and ECM binding cues, and provide a more relevant environment than
      possible with existing technologies such as flow chambers or 2D printed surfaces.
      Results: We found an overall increase in these processes with increasing
      concentration on both laminin and fibronectin gradients for a series of ovarian
      and breast cancer lines. Moreover, directness was higher for more metastatic
      cells, indicating that epithelial or mesenchymal state of the cell type governs
      the dynamics. However, the specifics of the speed and directedness depend on both
      the cell type and protein, thus we found that we must consider these processes
      collectively to obtain a self-consistent picture of the migration. For this
      purpose, we performed a linear discriminate analysis (LDA) and successfully
      classified the different cell types on the two protein gradients without
      molecular biology analysis. Conclusions: The bi-gradient structures are versatile
      tools to performing detailed studies of cell migration, specifically haptotxis.
      We further suggest the can be used in assessing efficacy of drug treatments
      targeted at specific matrix components.

PMID- 29177021
TI  - Romberg extrapolation for Euler summation-based cubature on regular regions.
AB  - Romberg extrapolation is a long-known method to improve the convergence rate of
      the trapezoidal rule on intervals. For simple regions such as the cube [Formula:
      see text] it is directly transferable to cubature in q dimensions. In this paper,
      we formulate Romberg extrapolation for Euler summation-based cubature on
      arbitrary q-dimensional regular regions [Formula: see text] and derive an
      explicit representation for the remainder term.

PMID- 29177022
TI  - Toward a Progress Indicator for Machine Learning Model Building and Data Mining
      Algorithm Execution: A Position Paper.
AB  - For user-friendliness, many software systems offer progress indicators for long
      duration tasks. A typical progress indicator continuously estimates the remaining
      task execution time as well as the portion of the task that has been finished.
      Building a machine learning model often takes a long time, but no existing
      machine learning software supplies a non-trivial progress indicator. Similarly,
      running a data mining algorithm often takes a long time, but no existing data
      mining software provides a nontrivial progress indicator. In this article, we
      consider the problem of offering progress indicators for machine learning model
      building and data mining algorithm execution. We discuss the goals and challenges
      intrinsic to this problem. Then we describe an initial framework for implementing
      such progress indicators and two advanced, potential uses of them, with the goal
      of inspiring future research on this topic.

PMID- 29177020
TI  - Epigenetic regulation of AXL and risk of childhood asthma symptoms.
AB  - Background: AXL is one of the TAM (TYRO3, AXL and MERTK) receptor tyrosine
      kinases and may affect numerous immune-related health conditions. However, the
      role for AXL in asthma, including its epigenetic regulation, has not been
      extensively studied. Methods: We investigated the association between AXL DNA
      methylation at birth and risk of childhood asthma symptoms at age 6 years. DNA
      methylation of multiple CpG loci across the regulatory regions of AXL was
      measured in newborn bloodspots using the Illumina HumanMethylation450 array on a
      subset of 246 children from the Children's Health Study (CHS). Logistic
      regression models were fitted to assess the association between asthma symptoms
      and DNA methylation. Findings were evaluated for replication in a separate
      population of 1038 CHS subjects using Pyrosequencing on newborn bloodspot
      samples. AXL genotypes were extracted from genome-wide data. Results: Higher
      average methylation of CpGs in the AXL gene at birth was associated with higher
      risk of parent-reported wheezing, and the association was stronger in girls than
      in boys. This relationship reflected the methylation status of the gene-body
      region near the 5' end, for which a 1% higher methylation level was significantly
      associated with a 72% increased risk of ever having wheezed by 6 years. The
      association of one CpG locus, cg00360107 was replicated using Pyrosequencing.
      Increased AXL methylation was also associated with lower mRNA expression level of
      this gene in lung tissue from the Cancer Genome Atlas (TCGA) dataset.
      Furthermore, AXL DNA methylation was strongly linked to underlying genetic
      polymorphisms. Conclusions: AXL DNA methylation at birth was associated with
      higher risk for asthma-related symptoms in early childhood.

PMID- 29177023
TI  - Adolescents and Self-Reported Physical Activity: An Evaluation of the Modified
      Godin Leisure-Time Exercise Questionnaire.
AB  - The Godin Leisure-Time Exercise Questionnaire assesses self-reported physical
      activity (PA) among adults, and was later modified for children. However, the
      modified version (Godin-Child Questionnaire) has not been validated among
      adolescents. This study evaluates the construct validity and test-retest
      reliability of the Godin-Child Questionnaire among adolescents. The study
      participants, sixth graders (age M= 11.06 +/- 0.436; 48% males, 48% Latino), were
      assessed at 2 time points (fall and spring: N= 139). First, the study determined
      whether adolescents accurately reported exercise intensity based on adolescents'
      ratings of perceived exertion (RPE) during moderate- and hard-intensity exercise
      tasks. Second, objective assessments of PA obtained using the Actigraph(r)
      accelerometer were correlated with PA self-reported on the Godin-Child
      Questionnaire. Third, test-retest correlations evaluated the Godin-Child
      Questionnaire for its reliability. Finally, interviews explored participants'
      interpretations of the Godin-Child Questionnaire. RPEs suggested that adolescents
      generally perceived exercise intensity accurately, with no significant
      differences between genders. There was a weak correlation between the Godin-Child
      Questionnaire and the Actigraph(r) during fall (r=.22, P< .05) and spring (r=.24,
      P<.05), with a significant correlation for males (P<.05) at both time periods.
      Test-retest correlations were acceptable (fall-spring r=.68; P<.001) and were
      equally strong among females and males. Interviews revealed that some respondents
      overlooked written directions. The Godin-Child Questionnaire may be a useful
      evaluative measure of self-reported physical activity for comparing activity
      levels across groups of adolescents, but may be less accurate for assessing
      physical activity on an individual level.

PMID- 29177024
TI  - Epidemiology of fragility fractures and fall prevention in the elderly: a
      systematic review of the literature.
AB  - Fragility fractures in the elderly is an ongoing concern for orthopaedic
      surgeons. A 50-year-old woman has a 40% chance of having a vertebral compression
      fracture in her lifetime. The incidence of vertebral fractures, reported to be
      more than 10 times higher than that of femoral fractures, is estimated as 1-1.5
      million per year in Japan. Vertebral fractures often occur without a fall,
      whereas the majority of nonvertebral fractures are the consequence of falls; the
      site of the nonvertebral fracture appears to be dictated by the type of fall.
      Distal radial fractures commonly occur as a consequence of hand protection during
      the fall. In older patients, falling load tends to directly affect shoulder and
      hip joints and lead to proximal humeral and femoral fractures. The incidence of
      vertebral fractures is increased in women over 50 yr of age, following the same
      trend as osteoporosis prevalence. Conversely, the mean age for proximal femoral
      fractures is around 80 yr, and more than 75% of femoral fractures occur in
      individuals over the age of 75. The prognostic risk of aging is 11-fold greater
      than that of reduced bone mineral density, and age is another risk factor for
      femoral fractures. Prophylactic therapy for osteoporosis and femoral fractures
      was shown to more effective in women in their 70s than in those over the age of
      80. Although several approaches, including exercise therapy, vitamin D
      administration, and environmental adjustment at home, have been reported to be
      effective in fall prevention, effective fracture prevention approaches in frail
      elderly individuals have not yet been well established.

PMID- 29177026
TI  - 2-Way k-Means as a Model for Microbiome Samples.
AB  - Motivation. Microbiome sequencing allows defining clusters of samples with shared
      composition. However, this paradigm poorly accounts for samples whose composition
      is a mixture of cluster-characterizing ones and which therefore lie in between
      them in the cluster space. This paper addresses unsupervised learning of 2-way
      clusters. It defines a mixture model that allows 2-way cluster assignment and
      describes a variant of generalized k-means for learning such a model. We
      demonstrate applicability to microbial 16S rDNA sequencing data from the Human
      Vaginal Microbiome Project.

PMID- 29177025
TI  - Acute Exposure to Cigarette Smoking Followed by Myocardial Infarction Aggravates
      Renal Damage in an In Vivo Mouse Model.
AB  - Cigarette smoking (S) is a risk factor for progressive chronic kidney disease,
      renal dysfunction, and renal failure. In this study, the effect of smoking on
      kidney function was investigated in a mouse model of myocardial infarction (MI)
      using 4 groups: control (C), smoking (S), MI, and S+MI. Histological analysis of
      S+MI group showed alterations in kidney structure including swelling of the
      proximal convoluted tubules (PCTs), thinning of the epithelial lining, focal loss
      of the brush border of PCTs, and patchy glomerular retraction. Molecular analysis
      revealed that nephrin expression was significantly reduced in the S+MI group,
      whereas sodium-hydrogen exchanger-1 (NHE-1) was significantly increased,
      suggesting altered glomerular filtration and kidney functions. Moreover, S+MI
      group, but not S alone, showed a significant increase in the expression of
      connective tissue growth factor (CTGF) and fibrotic proteins fibronectin (FN) and
      alpha-smooth muscle actin (SMA), in comparison to controls, in addition to a
      significant increase in mRNA levels of IL-6 and TNF-alpha inflammatory markers.
      Finally, reactive oxygen species (ROS) production was significantly accentuated
      in S+MI group concomitant with a significant increase in NOX-4 protein levels. In
      conclusion, smoking aggravates murine acute renal damage caused by MI at the
      structural and molecular levels by exacerbating renal dysfunction.

PMID- 29177027
TI  - Combination of Deep Recurrent Neural Networks and Conditional Random Fields for
      Extracting Adverse Drug Reactions from User Reviews.
AB  - Adverse drug reactions (ADRs) are an essential part of the analysis of drug use,
      measuring drug use benefits, and making policy decisions. Traditional channels
      for identifying ADRs are reliable but very slow and only produce a small amount
      of data. Text reviews, either on specialized web sites or in general-purpose
      social networks, may lead to a data source of unprecedented size, but identifying
      ADRs in free-form text is a challenging natural language processing problem. In
      this work, we propose a novel model for this problem, uniting recurrent neural
      architectures and conditional random fields. We evaluate our model with a
      comprehensive experimental study, showing improvements over state-of-the-art
      methods of ADR extraction.

PMID- 29177028
TI  - Introduction to Metrics in Person Centered Medicine Research.

PMID- 29177030
TI  - Is a positive intracutaneous test induced by penicillin mediated by histamine? A
      cutaneous microdialysis study in penicillin-allergic patients.
AB  - Background: Diagnostic workup of penicillin allergy comprises skin testing with
      penicillins, and patients are deemed allergic if skin test is positive. However,
      the literature suggests that skin test-positive patients may be challenge
      negative, indicating that the skin test may be falsely positive. Objective: To
      investigate real-time histamine release from a positive intracutaneous test
      induced by penicillin in patients with positive and negative challenges to
      penicillin. Methods: Skin microdialysis was performed in 21 penicillin-allergic
      patients with positive skin test, 13 non-allergic volunteers serving as negative
      controls, and 7 grass pollen-allergic patients serving as positive controls.
      Histamine was measured by microdialysis after skin test with
      penicillin/grass/NaCl. Penicillin challenge was subsequently performed in 12 of
      the patients. Results: Only 10/21 patients (47.6%) were skin test positive at
      microdialysis. During microdialysis 13 single intracutaneous tests were positive
      and histamine was detected in 4/13 occurring in four challenge positive patients.
      Thirteen/21 patients (61.9%) were deemed allergic to penicillin; eight had
      positive skin test. Two patients with positive skin test were challenge negative.
      In grass pollen allergic patients, 7/7 had a positive intracutaneous test to
      grass and all released histamine in the wheals. All 13 negative controls had
      negative intracutaneous test to penicillin and no histamine release. Conclusion:
      Histamine was only detected in the minority of positive intracutaneous tests with
      penicillin in penicillin-allergic patients. Other mediators may be involved.

PMID- 29177029
TI  - Tumorigenesis as a process of gradual loss of original cell identity and gain of
      properties of neural precursor/progenitor cells.
AB  - Cancer is a complex disease without a unified explanation for its cause so far.
      Our recent work demonstrates that cancer cells share similar regulatory networks
      and characteristics with embryonic neural cells. Based on the study, I will
      address the relationship between tumor and neural cells in more details. I
      collected the evidence from various aspects of cancer development in many other
      studies, and integrated the information from studies on cancer cell properties,
      cell fate specification during embryonic development and evolution. Synthesis of
      the information strongly supports that cancer cells share much more similarities
      with neural progenitor/stem cells than with mesenchymal-type cells and that
      tumorigenesis represents a process of gradual loss of cell or lineage identity
      and gain of characteristics of neural cells. I also discuss cancer EMT, a concept
      having been under intense debate, and possibly the true meaning of EMT in cancer
      initiation and development. This synthesis provides fresh insights into a unified
      explanation for and a previously unrecognized nature of tumorigenesis, which
      might not be revealed by studies on individual molecular events. The review will
      also present some brief suggestions for cancer research based on the proposed
      model of tumorigenesis.

PMID- 29177031
TI  - A protocol for clinical trial study of the effect of core stabilization exercises
      on spine kinematics during gait with and without load in patients with non
      specific chronic low back pain.
AB  - Background: Non-specific chronic low back pain (NCLBP) is a major public health
      and global socioeconomic burden with a variety of symptoms such as gait
      abnormality. Trunk stiffness and deep trunk muscles dysfunction known as guarding
      mechanism in gait are factors leading to abnormal movement pattern of the spine.
      Anterior load carriage task during gait is also challenged the trunk stability
      and its movement pattern. It will be therefore of interest to examine the effect
      of a Core Stabilization Training Program (CSTP) on the trunk and pelvis
      kinematics including variability and peak displacement during gait with and
      without load in NCLBP patients. Methods: Patients with NCLBP will participate in
      a program containing 16 sessions of CSTP and perceived pain, disability and
      kinematic will be evaluated with 100 mm visual analog scale (VAS), Oswestry
      Disability Index (ODI) and motion analyzing system respectively before and after
      the intervention. Participants will be asked to walk with self-selected
      comfortable speed for 3 times without load and 3 times with caring a load with
      hands. Discussions: We will quantify the effectiveness of CSTP on the kinematic
      of trunk, lumbar and pelvis during gait. Comparing the kinematic pattern and
      movement variability using CVo and CVp can contribute to better understand the
      motor control strategy and movement pattern of the spine during an anterior load
      carriage task between patients with NCLBP and healthy. Trial registration: IRCT
      number: IRCT2016080829264N1; pre-result.

PMID- 29177032
TI  - Stable isotopes can be used to infer the overwintering locations of prebreeding
      marine birds in the Canadian Arctic.
AB  - Although assessments of winter carryover effects on fitness-related breeding
      parameters are vital for determining the links between environmental variation
      and fitness, direct methods of determining overwintering distributions (e.g.,
      electronic tracking) can be expensive, limiting the number of individuals
      studied. Alternatively, stable isotope analysis in specific tissues can be used
      as an indirect means of determining individual overwintering areas of residency.
      Although increasingly used to infer the overwintering distributions of
      terrestrial birds, stable isotopes have been used less often to infer
      overwintering areas of marine birds. Using Arctic-breeding common eiders, we test
      the effectiveness of an integrated stable isotope approach (13-carbon, 15
      nitrogen, and 2-hydrogen) to infer overwintering locations. Knowing the
      overwinter destinations of eiders from tracking studies at our study colony at
      East Bay Island, Nunavut, we sampled claw and blood tissues at two known
      overwintering locations, Nuuk, Greenland, and Newfoundland, Canada. These two
      locations yielded distinct tissue-specific isotopic profiles. We then compared
      the isotope profiles of tissues collected from eiders upon their arrival at our
      breeding colony, and used a k-means cluster analysis approach to match arriving
      eiders to an overwintering group. Samples from the claws of eiders were most
      effective for determining overwinter origin, due to this tissue's slow growth
      rate relative to the 40-day turnover rate of blood. Despite taking an integrative
      approach using multiple isotopes, k-means cluster analysis was most effective
      when using 13-carbon alone to assign eiders to an overwintering group. Our
      research demonstrates that it is possible to use stable isotope analysis to
      assign an overwintering location to a marine bird. There are few examples of the
      effective use of this technique on a marine bird at this scale; we provide a
      framework for applying this technique to detect changes in the migration
      phenology of birds' responses to rapid changes in the Arctic.

PMID- 29177033
TI  - Evolutionarily significant units of the critically endangered leaf frog
      Pithecopus ayeaye (Anura, Phyllomedusidae) are not effectively preserved by the
      Brazilian protected areas network.
AB  - Protected areas (PAs) are essential for biodiversity conservation, but their
      coverage is considered inefficient for the preservation of all species. Many
      species are subdivided into evolutionarily significant units (ESUs) and the
      effectiveness of PAs in protecting them needs to be investigated. We evaluated
      the usefulness of the Brazilian PAs network in protecting ESUs of the critically
      endangered Pithecopus ayeaye through ongoing climate change. This species occurs
      in a threatened mountaintop ecosystem known as campos rupestres. We used
      multilocus DNA sequences to delimit geographic clusters, which were further
      validated as ESUs with a coalescent approach. Ecological niche modeling was used
      to estimate spatial changes in ESUs' potential distributions, and a gap analysis
      was carried out to evaluate the effectiveness of the Brazilian PAs network to
      protect P. ayeaye in the face of climate changes. We tested the niche overlap
      between ESUs to gain insights for potential management alternatives for the
      species. Pithecopus ayeaye contains at least three ESUs isolated in distinct
      mountain regions, and one of them is not protected by any PA. There are no
      climatic niche differences between the units, and only 4% of the suitable
      potential area of the species is protected in present and future projections. The
      current PAs are not effective in preserving the intraspecific diversity of P.
      ayeaye in its present and future range distributions. The genetic structure of P.
      ayeaye could represent a typical pattern in campos rupestres endemics, which
      should be considered for evaluating its conservation status.

PMID- 29177034
TI  - Maximum-likelihood approaches reveal signatures of positive selection in BMP15
      and GDF9 genes modulating ovarian function in mammalian female fertility.
AB  - Bone morphogenetic proteins (BMPs) and the growth factors (GDFs) play an
      important role in ovarian folliculogenesis and essential regulator of processes
      of numerous granulosa cells. BMP15 gene variations linked to various ovarian
      phenotypic consequences subject to the species, from infertility to improved
      prolificacy in sheep, primary ovarian insufficiency in women or associated with
      minor subfertility in mouse. To study the evolving role of BMP15 and GDF9, a
      phylogenetic analysis was performed. To find out the candidate gene associated
      with prolificacy in mammals, the nucleotide sequence of BMP15 and GDF9 genes was
      recognized under positive selection in various mammalian species. Maximum
      likelihood approaches used on BMP15 and GDF9 genes exhibited a robust divergence
      and a prompted evolution as compared to other TGFbeta family members.
      Furthermore, among 32 mammalian species, we identified positive selection signals
      in the hominidae clade resulting to 132D, 147E, 163Y, 191W, and 236P codon sites
      of BMP15 and 162F, 188K, 206R, 240A, 244L, 246H, 248S, 251D, 253L, 254F and other
      codon sites of GDF9. The positively selected amino acid sites such as Alanine,
      Lucien, Arginine, and lysine are important for signaling. In conclusion, this
      study evidences that GDF9 and BMP15 genes have rapid evolution than other TGFbeta
      family members and was subjected to positive selection in the mammalian clade.
      Selected sites under the positive selection are of remarkable significance for
      the particular functioning of the protein and consequently for female fertility.

PMID- 29177035
TI  - Predicting individual plant performance in grasslands.
AB  - Plant functional traits are widely used to predict community productivity.
      However, they are rarely used to predict individual plant performance in
      grasslands. To assess the relative importance of traits compared to environment,
      we planted seedlings of 20 common grassland species as phytometers into existing
      grassland communities varying in land-use intensity. After 1 year, we dug out the
      plants and assessed root, leaf, and aboveground biomass, to measure plant
      performance. Furthermore, we determined the functional traits of the phytometers
      and of all plants growing in their local neighborhood. Neighborhood impacts were
      analyzed by calculating community-weighted means (CWM) and functional diversity
      (FD) of every measured trait. We used model selection to identify the most
      important predictors of individual plant performance, which included phytometer
      traits, environmental conditions (climate, soil conditions, and land-use
      intensity), as well as CWM and FD of the local neighborhood. Using variance
      partitioning, we found that most variation in individual plant performance was
      explained by the traits of the individual phytometer plant, ranging between
      19.30% and 44.73% for leaf and aboveground dry mass, respectively. Similarly, in
      a linear mixed effects model across all species, performance was best predicted
      by phytometer traits. Among all environmental variables, only including land-use
      intensity improved model quality. The models were also improved by functional
      characteristics of the local neighborhood, such as CWM of leaf dry matter
      content, root calcium concentration, and root mass per volume as well as FD of
      leaf potassium and root magnesium concentration and shoot dry matter content.
      However, their relative effect sizes were much lower than those of the phytometer
      traits. Our study clearly showed that under realistic field conditions, the
      performance of an individual plant can be predicted satisfyingly by its
      functional traits, presumably because traits also capture most of environmental
      and neighborhood conditions.

PMID- 29177036
TI  - Sexual dimorphism, phenotypic integration, and the evolution of head structure in
      casque-headed lizards.
AB  - Sexes can differ in features associated with differential reproduction, which can
      be used during courtship or aggressive encounters. Some traits tend to evolve
      independently between sexes and emerge as sexually dimorphic within the
      organismal phenotype. We characterize such a relationship by estimating the
      phenotypic integration of the head morphology and modularity of the crest in the
      casque-headed lizards (Corytophanidae). In this clade, some species show extreme
      sexual dimorphism (e.g., head crests in the genus Basiliscus) while in others,
      both sexes are monomorphic. To characterize these patterns, we define phenotypic
      integration at the interspecific level as a pattern or network of traits
      evidenced by phylogenetically adjusted correlations that persist among species.
      At this level, modularity is an increased connectedness (e.g., higher
      correlation) among sections of these networks that persist in a lineage during
      the evolution of complex phenotypes. To test both concepts, we used phylogenetic
      geomorphometrics to characterize the head structure of corytophanid lizards,
      based on a time-calibrated phylogeny that includes candidate fossil ancestors. We
      found evidence of an older diversification of corytophanids than previously
      reported (~67 vs. ~23.5 MYA) and show that this clade includes two morphological
      head architectures: (1) Sexually dimorphic crests present in males that are
      evolving independently from the rest of the head structure, and (2) full
      integration of the head morphology in monomorphic species. We propose that both
      architectures are optimal evolutionary trajectories of the parietal crest bones
      in the head of these lizards. In sexually dimorphic species, these bones are
      elongated and thinner, and gave rise to the extended crest used in male courtship
      displays. In monomorphic species, the parietal crest grew thicker in both sexes
      to allow for a better insertion of muscles associated with a stronger bite.

PMID- 29177037
TI  - Unexpected mosaic distribution of two hybridizing sibling lineages in the
      teleplanically dispersing snail Stramonita haemastoma suggests unusual
      postglacial redistribution or cryptic invasion.
AB  - Molecular approaches have proven efficient to identify cryptic lineages within
      single taxonomic entities. Sometimes these cryptic lineages maybe previously
      unreported or unknown invasive taxa. The genetic structure of the marine
      gastropod Stramonita haemastoma has been examined in the Western Mediterranean
      and North-Eastern Atlantic populations with mtDNA COI sequences and three newly
      developed microsatellite markers. We identified two cryptic lineages,
      differentially fixed for alternative mtDNA COI haplogroups and significantly
      differentiated at microsatellite loci. The mosaic distribution of the two
      lineages is unusual for a warm-temperate marine invertebrate with a teleplanic
      larval stage. The Atlantic lineage was unexpectedly observed as a patch enclosed
      in the north of the Western Mediterranean Sea between eastern Spain and the
      French Riviera, and the Mediterranean lineage was found in Macronesian Islands.
      Although cyto-nuclear disequilibrium is globally maintained, asymmetric
      introgression occurs in the Spanish region where the two lineages co-occur in a
      hybrid zone. A first interpretation of our results is mito-nuclear discordance in
      a stable postglacial hybrid zone. Under this hypothesis, though, the location of
      genetic discontinuities would be unusual among planktonic dispersers. An
      alternative interpretation is that the Atlantic lineage, also found in Senegal
      and Venezuela, has been introduced by human activities in the Mediterranean area
      and is introgressing Mediterranean genes during its propagation, as theoretically
      expected. This second hypothesis would add an additional example to the growing
      list of cryptic marine invasions revealed by molecular studies.

PMID- 29177039
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1002/ece3.3223.].

PMID- 29177038
TI  - Genetic divergence between two phenotypically distinct bottlenose dolphin
      ecotypes suggests separate evolutionary trajectories.
AB  - Due to their worldwide distribution and occupancy of different types of
      environments, bottlenose dolphins display considerable morphological variation.
      Despite limited understanding about the taxonomic identity of such forms and
      connectivity among them at global scale, coastal (or inshore) and offshore (or
      oceanic) ecotypes have been widely recognized in several ocean regions. In the
      Southwest Atlantic Ocean (SWA), however, there are scarce records of bottlenose
      dolphins differing in external morphology according to habitat preferences that
      resemble the coastal-offshore pattern observed elsewhere. The main aim of this
      study was to analyze the genetic variability, and test for population structure
      between coastal (n = 127) and offshore (n = 45) bottlenose dolphins sampled in
      the SWA to assess whether their external morphological distinction is consistent
      with genetic differentiation. We used a combination of mtDNA control region
      sequences and microsatellite genotypes to infer population structure and levels
      of genetic diversity. Our results from both molecular marker types were congruent
      and revealed strong levels of structuring (microsatellites FST = 0.385, p < .001;
      mtDNA FST =  0.183, p < .001; PhiST = 0.385, p < .001) and much lower genetic
      diversity in the coastal than the offshore ecotype, supporting patterns found in
      previous studies elsewhere. Despite the opportunity for gene flow in potential
      "contact zones", we found minimal current and historical connectivity between
      ecotypes, suggesting they are following discrete evolutionary trajectories. Based
      on our molecular findings, which seem to be consistent with morphological
      differentiations recently described for bottlenose dolphins in our study area, we
      recommend recognizing the offshore bottlenose dolphin ecotype as an additional
      Evolutionarily Significant Unit (ESU) in the SWA. Implications of these results
      for the conservation of bottlenose dolphins in SWA are also discussed.

PMID- 29167731
TI  - Optimized purification strategies for the elimination of non-specific products in
      the isolation of GAD65-specific monoclonal autoantibodies.
AB  - Autoantibodies against antigens expressed by insulin-producing beta cells are
      circulating in both healthy individuals and patients at risk of developing Type 1
      diabetes. Recent studies suggest that another set of antibodies (anti-idiotypic
      antibodies) exists in this antibody/antigen interacting network to regulate auto
      reactive responses. Anti-idiotypic antibodies may block the antigen-binding site
      of autoantibodies or inhibit autoantibody expression and secretion. The
      equilibrium between autoantibodies and anti-idiotypic antibodies plays a critical
      role in mediating or preventing autoimmunity. In order to investigate the
      molecular mechanisms underlying such a network in autoimmunity and potentially
      develop neutralizing reagents to prevent or treat Type 1 diabetes, we need to
      produce autoantibodies and autoantigens with high quality and purity. Herein,
      using GAD65/anti-GAD65 autoantibodies as a model system, we aimed to establish
      reliable approaches for the preparation of highly pure autoantibodies suitable
      for downstream investigation.

PMID- 29167732
TI  - Blockchain protocols in clinical trials: Transparency and traceability of
      consent.
AB  - Clinical trial consent for protocols and their revisions should be transparent
      for patients and traceable for stakeholders. Our goal is to implement a process
      allowing the collection of patients' informed consent, which is bound to protocol
      revisions, storing and tracking the consent in a secure, unfalsifiable and
      publicly verifiable way, and enabling the sharing of this information in real
      time. For that, we will built a consent workflow using a rising technology called
      Blockchain. This is a distributed technology that brings a built-in layer of
      transparency and traceability. Additionally, it removes the need for third
      parties, and gives participative control to the peer-to-peer users. From a more
      general and prospective point of view, we believe Blockchain technology brings a
      paradigmatical shift to the entire clinical research field. We designed a Proof
      of-Concept protocol consisting of time-stamping each step of the patient's
      consent collection using Blockchain; thus archiving and historicising the consent
      through cryptographic validation in a securely unfalsifiable and transparent way.
      For each revision of the protocol, consent was sought again. We obtained a single
      document, in a standard open format, that accounted for the whole consent
      collection process: timestamped consent status with regards to each version of
      the protocol. This document cannot be corrupted, and can be checked on any
      dedicated public website. It should be considered as a robust proof of data. In
      the future, we think that the complex data flow of a clinical trial can be
      tracked using Blockchain. Moreover, a blockchain core functionality, named Smart
      Contract, can help prevent clinical trial events not to happen in the right
      chronological order: including patients before they consented or analysing case
      report forms data before freezing the database. This will help reaching
      reliability, security, and transparency, and could be a consistent step towards
      reproducibility.

PMID- 29167732
TI  - Blockchain protocols in clinical trials: Transparency and traceability of
      consent.
AB  - Clinical trial consent for protocols and their revisions should be transparent
      for patients and traceable for stakeholders. Our goal is to implement a process
      allowing the collection of patients' informed consent, which is bound to protocol
      revisions, storing and tracking the consent in a secure, unfalsifiable and
      publicly verifiable way, and enabling the sharing of this information in real
      time. For that, we will built a consent workflow using a rising technology called
      Blockchain. This is a distributed technology that brings a built-in layer of
      transparency and traceability. From a more general and prospective point of view,
      we believe Blockchain technology brings a paradigmatical shift to the entire
      clinical research field. We designed a Proof-of-Concept protocol consisting of
      time-stamping each step of the patient's consent collection using Blockchain;
      thus archiving and historicising the consent through cryptographic validation in
      a securely unfalsifiable and transparent way. For each revision of the protocol,
      consent was sought again. We obtained a single document, in a standard open
      format, that accounted for the whole consent collection process: timestamped
      consent status with regards to each version of the protocol. This document cannot
      be corrupted, and can be checked on any dedicated public website. It should be
      considered as a robust proof of data. However, in a live clinical trial, the
      authentication system should be strengthened in order to remove the need for
      third parties, here the trial stakeholders, and give participative control to the
      peer-to-peer users. In the future, we think that the complex data flow of a
      clinical trial can be tracked using Blockchain, that a blockchain core
      functionality, named Smart Contract, could help prevent clinical trial events not
      to happen in the right chronological order: for example including patients before
      they consented or analysing case report forms data before freezing the database.
      Globally, we think Blockchain will help with reliability, security, and
      transparency, and could be a consistent step towards reproducibility.

PMID- 29167733
TI  - A 4-week, lifestyle-integrated, home-based exercise training programme elicits
      improvements in physical function and lean mass in older men and women: a pilot
      study.
AB  - BACKGROUND: Developing alternative exercise programmes that can alleviate certain
      barriers to exercise such as psychological, environmental or socio-economical
      barriers, but provide similar physiological benefits e.g. increases in muscle
      mass and strength, is of grave importance. This pilot study aimed to assess the
      efficacy of an unsupervised, 4-week, whole-body home-based exercise training
      (HBET) programme, incorporated into daily living activities, on skeletal muscle
      mass, power and strength. METHODS: Twelve healthy older volunteers (63+/-3 years,
      7 men: 5 women, BMI: 29+/-1 kg/m2) carried out the 4-week "lifestyle-integrated"
      HBET of 8 exercises, 3x12 repetitions each, every day. Before and after HBET, a
      number of physical function tests were carried out: unilateral leg extension 1-RM
      (one- repetition maximum), MVC (maximal voluntary contraction) leg extension,
      lower leg muscle power (via Nottingham Power Rig), handgrip strength and SPPBT
      (short physical performance battery test). A D 3-Creatine method was used for
      assessment of whole-body skeletal muscle mass, and ultrasound was used to measure
      the quadriceps cross-sectional area (CSA) and vastus lateralis muscle thickness.
      RESULTS: Four weeks HBET elicited significant (p<0.05) improvements in leg muscle
      power (276.7+/-38.5 vs. 323.4+/-43.4 W), maximal voluntary contraction (60
      degrees : 154.2+/-18.4 vs. 168.8+/-15.2 Nm, 90 degrees : 152.1+/-10.5 vs. 159.1+/
      11.4 Nm) and quadriceps CSA (57.5+/-5.4 vs. 59.0+/-5.3 cm 2), with a trend for an
      increase in leg strength (1-RM: 45.7+/-5.9 vs. 49.6+/-6.0 kg, P=0.08). This was
      despite there being no significant differences in whole-body skeletal muscle
      mass, as assessed via D 3-Creatine. CONCLUSIONS: This study demonstrates that
      increases in multiple aspects of muscle function can be achieved in older adults
      with just 4-weeks of "lifestyle-integrated" HBET, with a cost-effective means.
      This training mode may prove to be a beneficial alternative for maintaining
      and/or improving muscle mass and function in older adults.

PMID- 29167735
TI  - A review of data sharing statements in observational studies published in the
      BMJ: A cross-sectional study.
AB  - In order to understand the current state of data sharing in observational
      research studies, we reviewed data sharing statements of observational studies
      published in a general medical journal, the British Medical Journal. We found
      that the majority (63%) of observational studies published between 2015 and 2017
      included a statement that implied that data used in the study could not be
      shared. If the findings of our exploratory study are confirmed, room for
      improvement in the sharing of real-world or observational research data exists.

PMID- 29177045
TI  - Correlation of Carbon Dots' Light-Activated Antimicrobial Activities and
      Fluorescence Quantum Yield.
AB  - This study investigated the photo-activated antibacterial function of a series of
      specifically prepared carbon dots with 2,2'-(ethylenedioxy)bis(ethylamine) as the
      surface functionalization molecule (EDA-CDots), whose fluorescence quantum yields
      (PhiF) ranged from 7.5% to 27%. The results revealed that the effectiveness of
      CDots' photo-activated bactericidal function was correlated with their observed
      PhiF values. The antimicrobial activities of these EDA-CDots against both Gram
      negative and Gram positive model bacterial species (E. coli and Bacillus
      subtilis, respectively) were also evaluated under conditions of varying other
      experimental parameters including dot concentrations and treatment times.
      Optimization of the bactericidal effect of the EDA-CDots by a combination of the
      selected PhiF, concentration and treatment time was explored, and mechanistic
      implications of the results are discussed.

PMID- 29177047
TI  - Virucidal efficacy of peracetic acid for instrument disinfection.
AB  - Background: Various peracetic-acid (PAA)-based products for processing flexible
      endoscopes on the market are often based on a two-component system including a
      cleaning step before the addition of PAA as disinfectant. The peracetic acid
      concentrations in these formulations from different manufacturers are ranging
      from 400 to 1500 ppm (part per million). These products are used at temperatures
      between 20  degrees C and 37  degrees C. Since information on the virus
      inactivating properties of peracetic acid at different concentrations and
      temperature is missing, it was the aim of the study to evaluate peracetic acid
      solutions against test viruses using the quantitative suspension test, EN 14476.
      In addition, further studies were performed with the recently established
      European pre norm (prEN 17111:2017) describing a carrier assay for simulating
      practical conditions using frosted glass. Methods: In the first step of
      examination, different PAA solutions between 400 and 1500 ppm were tested at 20 
      degrees C, 25  degrees C, and 35  degrees C with three test viruses (adenovirus,
      murine norovirus and poliovirus) necessary for creating a virucidal action
      according to the European Norm, EN 14476. A second step for simulating practical
      conditions based on prEN 17111:2017 followed by spreading a test virus together
      with soil load onto a glass carrier which was immerged into a peracetic acid
      solution. A fixed exposure time of five minutes was used in all experiments.
      Results: In the quantitative suspension test 1500 ppm PAA solution was needed at
      35  degrees C for five minutes for the inactivation of poliovirus, whereas only
      400 ppm at 20  degrees C for adeno- and murine norovirus were necessary. In the
      carrier assay 400 ppm peracetic acid at 20  degrees C were sufficient for
      adenovirus inactivation, whereas 600 ppm PAA were needed at 25  degrees C and 35 
      degrees C and 1000 ppm at 20  degrees C for murine norovirus. A PAA solution with
      1000 ppm at 35  degrees C was required for complete inactivation of poliovirus.
      However, a dramatically decrease of titer after the drying and immerging could be
      observed. In consequence, a four log reduction of poliovirus titer could not be
      achieved in the carrier test. Conclusion: In summary, 1500 ppm PAA at 35  degrees
      C was necessary for a virucidal action in the quantitative suspension test. After
      passing the requirements of the suspension test, additional examinations with
      adeno- and murine norovirus on glass carriers based on prEN 17111:2017 will not
      additionally contribute to the final claim of an instrument disinfectant for
      virucidal efficacy. This is due to the great stability of poliovirus in the
      preceded quantitative suspension test and the fact that poliovirus could not
      serve as test virus in the following carrier assay.

PMID- 29177046
TI  - The Gene Ontology of eukaryotic cilia and flagella.
AB  - Background: Recent research into ciliary structure and function provides
      important insights into inherited diseases termed ciliopathies and other cilia
      related disorders. This wealth of knowledge needs to be translated into a
      computational representation to be fully exploitable by the research community.
      To this end, members of the Gene Ontology (GO) and SYSCILIA Consortia have worked
      together to improve representation of ciliary substructures and processes in GO.
      Methods: Members of the SYSCILIA and Gene Ontology Consortia suggested additions
      and changes to GO, to reflect new knowledge in the field. The project initially
      aimed to improve coverage of ciliary parts, and was then broadened to cilia
      related biological processes. Discussions were documented in a public tracker. We
      engaged the broader cilia community via direct consultation and by referring to
      the literature. Ontology updates were implemented via ontology editing tools.
      Results: So far, we have created or modified 127 GO terms representing parts and
      processes related to eukaryotic cilia/flagella or prokaryotic flagella. A growing
      number of biological pathways are known to involve cilia, and we continue to
      incorporate this knowledge in GO. The resulting expansion in GO allows more
      precise representation of experimentally derived knowledge, and SYSCILIA and GO
      biocurators have created 199 annotations to 50 human ciliary proteins. The
      revised ontology was also used to curate mouse proteins in a collaborative
      project. The revised GO and annotations, used in comparative 'before and after'
      analyses of representative ciliary datasets, improve enrichment results
      significantly. Conclusions: Our work has resulted in a broader and deeper
      coverage of ciliary composition and function. These improvements in ontology and
      protein annotation will benefit all users of GO enrichment analysis tools, as
      well as the ciliary research community, in areas ranging from microscopy image
      annotation to interpretation of high-throughput studies. We welcome feedback to
      further enhance the representation of cilia biology in GO.

PMID- 29177048
TI  - Impact of single room design on the spread of multi-drug resistant bacteria in an
      intensive care unit.
AB  - Background: Cross-transmission of nosocomial pathogens occurs frequently in
      intensive care units (ICU). The aim of this study was to investigate whether the
      introduction of a single room policy resulted in a decrease in transmission of
      multidrug-resistant (MDR) bacteria in an ICU. Methods: We performed a
      retrospective study covering two periods: between January 2002 and April 2009
      (old-ICU) and between May 2009 and March 2013 (new-ICU, single-room). These
      periods were compared with respect to the occurrence of representative MDR Gram
      negative bacteria. Routine microbiological screening, was performed on all
      patients on admission to the ICU and then twice a week. Multi-drug resistance was
      defined according to a national guideline. The first isolates per patient that
      met the MDR-criteria, detected during the ICU admission were included in the
      analysis. To investigate the clonality, isolates were genotyped by DiversiLab
      (bioMerieux, France) or Amplified Fragment Length Polymorphism (AFLP). To
      guarantee the comparability of the two periods, the 'before' and 'after' periods
      were chosen such that they were approximately identical with respect to the
      following factors: number of admissions, number of beds, bed occupancy rate, per
      year and month. Results: Despite infection prevention efforts, high prevalence of
      MRD bacteria continue to occur in the original facility. A marked and sustained
      decrease in the prevalence of MDR-GN bacteria was observed after the migration to
      the new ICU, while there appear to be no significant changes in the other
      variables including bed occupancy and numbers of patient admissions. Conclusion:
      Single room ICU design contributes significantly to the reduction of cross
      transmission of MRD-bacteria.

PMID- 29177049
TI  - A 10-year follow-up study of completers versus dropouts following treatment with
      an integrated cognitive-behavioral group therapy for eating disorders.
AB  - Background: Cognitive-behavioral therapy (CBT) has been recommended for the
      treatment of eating disorders, and group therapy is known to have certain
      advantages over individual therapy. The aim of the current study was to compare
      the 10-year prognosis of patients who completed integrated group CBT with those
      who dropped out and to examine the effect of completion of group CBT on the
      prognosis. Methods: The participants were 65 adult patients with eating
      disorders. All patients were women and Japanese. The average age (19-37) of the
      patients was 25.1 +/- 3.8 years, and the average body mass index (BMI) was 17.7
      +/- 2.0. We conducted integrated group CBT with the patients and compared eating
      disorder symptoms, mood states, coping styles, and self-esteem before and after
      therapy. Furthermore, we compared clinical features and the 10-year prognosis of
      patients who completed the treatment and those who dropped out. Results: After 10
      sessions of group therapy, Eating Attitudes Test scores, Profile of Mood States
      depression scores, and Coping Inventory for Stressful Situations emotion-oriented
      scores decreased, while Rosenberg's Self-Esteem Scale scores increased. Regarding
      the results of the 10-year follow up, the completer group had more patients with
      a good prognosis. In contrast, the dropout group had more patients with a poor
      prognosis. Conclusions: Those who completed the integrated group CBT had a good
      prognosis. Group therapy gives the patients an opportunity to form peer
      relationships, and helps them to develop communication and socialization skills.
      Furthermore, in the group therapy sessions, the patients develop self-awareness
      by listening to other members of the group and they also develop interpersonal
      relationships. This effect may be temporary, but experience of group therapy may
      provide hope for the patient and increase the chance of the patient continuing
      treatment. Trial registration: Retrospectively registered in University Hospital
      Medical Information Network in Japan: No. 000028868 (May 19th, 2017).

PMID- 29177050
TI  - Effect of regular exercise training on changes in HbA1c, BMI and VO2max among
      patients with type 2 diabetes mellitus: an 8-year trial.
AB  - Objective: The effects of regular exercise on the health promotion of patients
      with type 2 diabetes mellitus (T2DM) have been well documented. The present study
      investigated the long-term effects of regular exercise training on biological
      indicators among these patients. Methods: In this quasi-experimental trial with
      pretest-post-test design, 65 patients with T2DM aged 33-69 years (experiment
      (35), control (30)) participated. After 8 years of conducting the program, the
      data on 30 patients (experiment (15), control (15)) were entered into analysis.
      The training program included aerobic exercise three sessions per week, 90 min,
      50%-80% VO2max. Before and after the intervention, the biological indicators
      (hemoglobin A1c (HbA1c), body mass index (BMI) and VO2max) were measured. Data
      were analyzed using multivariate analysis of covariance. Results: Our long-term
      exercise training program had a significant effect on HbA1C, BMI and Vo2max
      (P<0.05). Compared with patients in the control group, HbA1c was significantly
      reduced and BMI and VO2max were significantly improved among the experiment
      group. Conclusions: Long-term regular physical activity training was found to be
      helpful in improving glycemic control, body composition and cardiovascular
      fitness among patients with T2DM. Long-term continuous physical activity offsets
      the deteriorations of biological indicators found in the control group. Further
      research, with a particular focus on practical and real-world programming, is
      needed to determine the responsive health outcomes of such long-term programs on
      the patients.

PMID- 29177051
TI  - Type 2 diabetes in general practice in Norway 2005-2014: moderate improvements in
      risk factor control but still major gaps in complication screening.
AB  - Objective: To assess the status of type 2 diabetes care in general practice and
      changes in the quality of care between 2005 and 2014, and to identify areas of
      diabetes care requiring improvement. Research design and methods: Two cross
      sectional surveys were performed that included patients with type 2 diabetes in
      selected areas (n=9464 in 2014, n=5463 in 2005). Quality of care was assessed
      based on key recommendations in national guidelines. Differences in clinical
      performance between 2005 and 2014 were assessed in regression models adjusting
      for age, sex, counties and clustering within general practices. Results:
      Treatment targets were achieved in a higher proportion of patients in 2014
      compared with 2005: hemoglobin A1c <=7.0% (<=53 mmol/mol) in 62.8% vs 54.3%,
      blood pressure <=135/80 mm Hg in 44.9% vs 36.6%, and total cholesterol <=4.5
      mmol/L in 49.9% vs 33.5% (all adjusted P<=0.001). Regarding screening procedures
      for microvascular complications, fewer patients had recorded an eye examination
      (61.0% vs 71.5%, adjusted P<0.001), whereas more patients underwent monofilament
      test (25.9% vs 18.7%, adjusted P<0.001). Testing for albuminuria remained low
      (30.3%) in 2014. A still high percentage were current smokers (22.7%).
      Conclusions: We found moderate improvements in risk factor control for patients
      with type 2 diabetes in general practice during the last decade, which are
      similar to improvements reported in other countries. We report major gaps in the
      performance of recommended screening procedures to detect microvascular
      complications. The proportion of daily smokers remains high. We suggest
      incentives to promote further improvements in diabetes care in Norway.

PMID- 29177052
TI  - Biomarkers of tubulointerstitial damage and function in type 1 diabetes.
AB  - Objective: To evaluate biomarkers of renal tubulointerstitial damage and function
      in type 1 diabetes with and without diabetic kidney disease. Research design and
      methods: Cross-sectional case-control study of Diabetes Control and Complications
      Trial/Epidemiology of Diabetes Interventions and Complications Study
      participants. Cases (N=43) had incident persistent estimated glomerular
      filtration rate (eGFR) <60 mL/min/1.73 m2 with urinary albumin excretion >300
      mg/24 hour. Controls (N=43) had persistent eGFR >90 mL/min/1.73 m2 and urinary
      albumin excretion <30 mg/24 hour. Urinary and plasma biomarkers reflecting
      tubular injury, inflammation, fibrosis, secretion, and synthetic function were
      measured from stored specimens collected at the first study visit with reduced
      eGFR (for case participants) or the corresponding study year (for control
      participants). Results: Mean (SD) age was 51 (9) and 50 (8) years for case and
      control participants, and mean (SD) duration of diabetes was 30 (6) and 30 (5)
      years, respectively. Mean (SD) eGFR was 39 (14) and 103 (9) mL/min/1.73 m2 for
      case and control participants, and mean (SD) albumin excretion rate was 1978
      (2914) and 10 (7) mg/day, respectively. Comparing cases with controls,
      significant differences were observed in each measured biomarker, including urine
      epidermal growth factor (mean 5.3 vs 21.2 MUg/g creatinine for case vs control
      participants, respectively), urine monocyte chemoattractant protein-1 (596 vs 123
      ng/g creatinine), urine galectin-3 (168 vs 52 MUg/g creatinine), plasma soluble
      tubular necrosis factor receptor-1 (3695 vs 1022 pg/mL), plasma galectin-3 (21.3
      vs 11.0 ng/mL), urinary clearances of hippurate (70 vs 167 mL/min) and
      cinnamoylglycine (77 vs 317 mL/min), and plasma arginine-citrulline ratio (5.6 vs
      7.7 MUg/MUg), each P<0.001. Conclusions: Marked abnormalities in biomarkers of
      kidney tubular injury, inflammation, fibrosis, secretion, and synthetic function
      accompany reduced eGFR and albuminuria in type 1 diabetes. Trial registration
      number: NCT00360893, NCT00360815.

PMID- 29177053
TI  - Evaluation of a single-administration ototopical treatment for canine otitis
      externa: a randomised trial.
AB  - Objective: To evaluate the efficacy and safety of a new, single-administration
      Otic Solution containing florfenicol, terbinafine and mometasone furoate for the
      treatment of canine otitis externa (OE). Design: The clinical efficacy and safety
      study was a multicentre, controlled, masked and randomised field study conducted
      over 30 days. Two hundred and twenty-one (221) client-owned dogs of varying
      breeds with diagnosed bacterial and/or fungal OE were enrolled. Procedure: Dogs
      were randomised to either Otic Solution or control groups. Evaluations were
      conducted over a minimum period of 30 days with a primary effectiveness endpoint
      based on the improvement in a clinical severity score at the final visit (day
      30). Safety analyses were based on clinical and laboratory parameters and the
      occurrence of adverse events. Results: The Otic Solution group demonstrated a
      significantly higher treatment success rate compared with that observed for the
      control group (72.5 per cent v 11.1 per cent, P value=0.0001) for cases of OE
      caused by Staphylococcus pseudintermedius and Malassezia pachydermatis. No
      significant safety findings were reported. Conclusions/clinical relevance: This
      new ototopical formulation provides safe and effective treatment of canine OE and
      is an important alternative antimicrobial for this indication. The single
      administration dosage regimen eliminates opportunities for client dosage
      administration errors and medication stockpiling.

PMID- 29177054
TI  - Increase in branched-chain amino acids due to acidemia in neonatal calves with
      diarrhoea.
AB  - The aim of this study was to investigate the relationships between acid-base
      status and plasma branched-chain amino acids (BCAA) concentration in calves with
      diarrhoea for intravenous nutrition, especially with amino acid solution in
      calves with diarrhoea. Thirty-four Holstein calves aged 11.0+/-5.9 days old were
      enrolled in this study. In 10 of 34 calves exhibiting clinical signs of
      diarrhoea, severe dehydration and acidemia were observed (severe group: pH:
      7.04+/-0.11, base excess (BE): -17.4+/-4.5) based on blood gas analysis. In 7 of
      34 calves exhibiting clinical signs of diarrhoea, mild dehydration and acidemia
      were observed (mild group: pH: 7.29+/-0.06, BE: 0.0+/-5.2). The other 17 calves
      did not exhibit dehydration or acidemia (pH: 7.41+/-0.02, BE: 11.2+/-3.5) based
      on clinical signs and blood gas analysis. The plasma concentration of BCAA was
      significantly higher in the severe group than in the other groups. In addition,
      the blood pH and plasma concentrations of BCAA (r=-0.41, P<0.05) were
      significantly and negatively correlated. As calves with metabolic acidosis have
      increased plasma BCAA concentrations due to hypermetabolic states of proteolysis,
      amino acid solutions containing low concentrations of BCAA may be useful to
      gradually correct the negative nitrogen balance.

PMID- 29177055
TI  - Population characteristics of golden retriever lifetime study enrollees.
AB  - Background: Studying cancer and other diseases poses a problem due to their
      protracted and multifactorial nature. Prospective studies are useful to
      investigate chronic disease processes since collection of lifestyle information,
      exposure data and co-incident health issues are collected before the condition
      manifests. The Golden Retriever Lifetime Study is one of the first prospective
      studies following privately-owned dogs throughout life to investigate the
      incidence and risk factors for disease outcomes, especially cancer.Owners of
      golden retrievers in the contiguous United States volunteered their dogs in early
      life. Owners and veterinarians complete online questionnaires about health status
      and lifestyle; dogs undergo a physical examination and collection of biological
      samples annually. The data presented summarize the initial study visits and the
      corresponding questionnaires for 3044 dogs in the cohort. Results: The median age
      of dogs at enrollment was 14.0 months (interquartile range (IQR): 8-20 months).
      Approximately half of the population had undergone gonadectomy by their initial
      study visit. Medical conditions reported at enrollment consisted primarily of
      integumentary, gastrointestinal and urinary dysfunction. A large majority of the
      dogs have a record of having received preventive care (vaccines, parasiticides,
      flea and heartworm prevention) by the time of the initial study visit. Clinical
      pathology data were unremarkable. Conclusions: This study represents one of the
      first lifetime observational investigations in veterinary medicine. The
      population characteristics reported here indicate a healthy cohort of golden
      retrievers cared for by owners committed to their dogs' health. Data acquired
      over the study period will provide valuable information about genetic, dietary
      and environmental risk factors associated with disease in golden retrievers and a
      framework for future prospective studies in veterinary medicine.

PMID- 29177056
TI  - Physical activity and central adiposity in a cohort of African-American adults.
AB  - Background: Visceral adipose tissue (VAT) is known as an independent predictor of
      cardiometabolic risk and all-cause mortality, while increased physical activity
      has been shown to improve cardiometabolic risk. The purpose of the present study
      was to determine whether or not there is an association between objectively
      measured physical activity and VAT in a community-based cohort of African
      American adults, a population at higher-than-average risk for cardiometabolic
      diseases. Methods: Free-living physical activity was quantified using
      accelerometry while VAT and abdominal subcutaneous fat were estimated using dual
      x-ray absorptiometry in a cohort of African Americans, ages 30-50 years, enrolled
      in the Modeling the Epidemiologic Transition Study. Univariate and multivariate
      analyses were used to determine the degree of association comparing moderate-to
      vigorous physical activity (MVPA), vigorous activity, and sedentary behavior with
      measures of central adiposity including VAT, subcutaneous fat, and waist
      circumference. Results: A total of 271 individuals with complete data were
      included in the analyses. Women, on average, had significantly more VAT and
      abdominal subcutaneous fat than men. There were statistically significant inverse
      univariate correlations between MVPA and measures of abdominal adiposity (-0.30,
      p < 0.001) and activity counts and adiposity (-0.31, p < 0.001) among both sexes.
      These significant associations remained after controlling for age, sex, and
      smoking status; neither alcohol consumption nor employment status were associated
      with abdominal adiposity. Time in sedentary behavior was not meaningfully
      associated with central adiposity in either sex (women: -0.02, p = 0.79; men: 
      0.21, p = 0.04). Conclusions: To our knowledge, this study is the first to
      identify significant inverse associations between MVPA and measures of central
      adiposity among African American adults from a community-based cohort using an
      objective measure of physical activity and a validated quantitative imaging
      technique.

PMID- 29177057
TI  - Motivation and perceived competence for healthy eating and exercise among
      overweight/obese adolescents in comparison to normal weight adolescents.
AB  - Background: The current literature on determinants of behavior change in weight
      management lacks sufficient studies on type of motivation among
      children/adolescents, on perceived competence, and in relation to healthy eating.
      This study aimed to investigate type of motivation and levels of perceived
      competence for healthy diet and exercise, as well as general self efficacy among
      adolescents. We hypothesized that overweight/obese adolescents would demonstrate
      lower autonomous motivation and perceived competence regarding diet and exercise,
      and lower self-efficacy in general, and that the scores would be influenced by
      socioeconomic factors. Methods: Normal weight (n = 40, body mass index < 85% for
      age and gender) and overweight or obese adolescents (n = 60, body mass index >=
      85% for age and gender) aged 13-18 years were recruited from pediatric ambulatory
      clinics. Information was collected about demographics, socioeconomic factors, and
      lifestyle behaviors. The study subjects completed a survey including the
      Treatment Self-Regulation Questionnaire (TSRQ) and the Perceived Competence Scale
      (PCS) for healthy eating and exercise, and the General Self-Efficacy Scale
      (GSES). Composite scores for the three scales were compared between the two
      groups using the using the two-sample t-test (for normal data) or the Mann
      Whitney U test (for non-parametric data). Relationships between the composite
      scores and patient characteristics were determined using Pearson or Spearman's
      correlations. Results: The average age of the total cohort was 15.9 +/- 1.9
      years. 54% were female, and 82% identified as Latino/Hispanic. In comparison to
      normal weight subjects, overweight/obese adolescents exhibited higher scores for
      controlled motivation (mean +/- standard deviation 28.3 +/- 9.3 vs 18.1 +/- 8.1)
      and higher perceived competence [median and 25-75% interquartile range 22.5 (19.0
      26.0) vs 20.0 (15.5-25.0)] in relation to eating a healthy diet. These
      differences persisted after adjustment for age, sex, paternal education, and
      family income. Conclusions: Overweight/obese adolescents did not lack autonomous
      motivation but demonstrated higher controlled motivation and perceived competence
      for healthy eating in comparison to normal weight adolescents, independent of
      socioeconomic factors. In the clinical practice of weight management, providers
      should carefully assess adolescents for type of motivation and perceived
      competence, while accounting for potential barriers to behavior change.

PMID- 29177058
TI  - Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic
      cardiomyopathy.
AB  - Objective: Sarcomeric gene mutation carriers without overt left ventricular
      hypertrophy (G+/LVH-) can harbour subclinical changes in cardiovascular structure
      and function that precede the development of hypertrophic cardiomyopathy (HCM).
      We sought to investigate if circulating biomarkers of cardiovascular stress and
      collagen metabolism among G+/LVH- individuals, measured at rest and following
      exercise provocation, yield further insights into the underlying biology of HCM.
      Methods: We studied 76 individuals with overt HCM, 50 G+/LVH- individuals and 41
      genotype-negative related controls enrolled in a cross-sectional, multicentre
      observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type
      natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2)
      and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal
      telopeptide of type I collagen; galectin-3; periostin) were measured. Results:
      Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH-
      subjects and controls at rest, along with an exaggerated increase in NT-proBNP
      and hsTnI in response to exercise. We found no detectable differences in resting
      or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis
      among G+/LVH- individuals compared with healthy controls despite subtle
      echocardiographic differences in cardiac structure and function. Conclusion:
      Dynamic exercise testing exaggerated resting differences in natriuretic peptides
      and troponin elevations among individuals with overt HCM. In contrast, we found
      no differences in biomarker profiles of cardiovascular stress and fibrosis among
      G+/LVH- individuals compared with controls even after maximal exercise
      provocation. Our findings highlight the need for continued investigation into
      early phenotypes of sarcomeric gene mutations and the evolution of HCM.

PMID- 29177059
TI  - Gender differences in the decrease of in-hospital mortality in patients with
      acute myocardial infarction during the last 20 years in Switzerland.
AB  - Objective: To assess temporal trends of in-hospital mortality in patients with
      acute myocardial infarction (AMI) enrolled in the Swiss nationwide registry (AMIS
      Plus) over the last 20 years with regard to gender, age and in-hospital
      treatment. Methods: All patients with AMI from 1997 to 2016 were stratified
      according to ST-segment elevation myocardial infarction (STEMI) or non-STEMI
      (NSTEMI), and gender using logistic regression analyses. Results: Among 51 725
      patients, 30 398 (59%) had STEMI and 21 327 (41%) had NSTEMI; 73% were men
      (63.9+/-12.8 years) and 27% were women (71.7+/-12.5 years). Over 20 years, crude
      in-hospital STEMI mortality decreased from 9.8% to 5.5% in men and from 18.3% to
      6.9% in women. In patients with NSTEMI, it decreased from 7.1% to 2.1% in men and
      from 11.0% to 3.6% in women. After adjustment for age, mortality decreased per
      additional admission year by 3% in men with STEMI (OR 0.97, 95% CI 0.96 to 0.98,
      P<0.001), by 5% in women with STEMI (OR 0.95, 95% CI 0.93 to 0.96, P<0.001), by
      6% in men with NSTEMI (OR 0.94, 95% CI 0.93 to 0.96, P<0.001) and by 5% in women
      with NSTEMI (OR 0.95, 95% CI 0.93 to 0.97, P<0.001). In patients <60 years, a
      decrease in mortality was seen in women with STEMI (OR 0.94, 95% CI 0.90 to 0.99,
      P=0.025) and NSTEMI (OR 0.87, 95% CI 0.80 to 0.94, P<0.001) but not in men with
      STEMI (OR 1.01, 95% CI 0.98 to 1.04, P=0.46) and NSTEMI (OR 0.98, 95% CI 0.94 to
      1.03, P=0.41). The mortality decrease in patients with AMI was closely associated
      with the increase in reperfusion therapy. Conclusion: From 1997 to 2016, in
      hospital mortality of patients with AMI in Switzerland has halved and was more
      pronounced in women, particularly in the age category <60 years. Trial
      registration number: NCT01305785; Results.

PMID- 29177060
TI  - Predictors of incident proteinuria among patients with SLE.
AB  - Objective: To identify fixed and time-varying predictors of incident proteinuria.
      Methods: This analysis was based on patients who did not have a history of
      diabetes and who did not have a prior episode of renal involvement. We defined an
      incident case of proteinuria as two or more measures of urine protein to
      creatinine ratio (or 24-hour protein measure) greater than 0.5 in two visits
      separated by more than 30 days and less than 180 days. We estimated rates of
      incident proteinuria in subgroups of patients with lupus defined by time
      invariant and time-varying predictors. Results: Among 895 patients included in
      the analysis, 840 (94%) were female, and 518 (58%) were Caucasian, 304 (34%)
      African-American, with mean age of 42 years at the start of follow-up. We
      observed 57 incident cases of proteinuria over a span of 4669 person-years of
      cohort follow-up. The overall rate of incident proteinuria was 12.2 per 1000
      person-years. The rate was significantly lower among those of older age, and
      higher among those who were not Caucasian. In those with a very low C3 measure in
      a previous cohort visit, the rate was increased by a factor of 16.1 and in those
      with a very low C4 by 16.3. The rate among those prescribed hydroxychloroquine or
      ACE inhibitors/ARB was similar to those not on them. Conclusions: Older patients
      with SLE are at low risk for developing proteinuria. There was not strong
      evidence that hydroxychloroquine or angiotensin-converting-enzyme (ACE) inhibitor
      reduced the risk of proteinuria. The highest rates of incident proteinuria were
      among those with recent low complement.

PMID- 29177061
TI  - Illness representations of systemic lupus erythematosus and systemic sclerosis: a
      comparison of patients, their rheumatologists and their general practitioners.
AB  - Objective: Discrepancies in illness representations between patients and
      physicians result in treatment difficulties, decreased well-being of patients and
      misunderstandings and disrupted communication. Hence, the objective of this study
      was to compare illness perceptions of individual patients with systemic lupus
      erythematosus (SLE) and systemic sclerosis (SSc), their rheumatologists and their
      general practitioners (GPs) and explore potential differences. Methods: This
      study has a cross-sectional design. Patients with SLE and SSc, who were followed
      at the rheumatology department of the University Hospitals Leuven (Belgium),
      completed the revised Illness Perception Questionnaire which measures patients'
      perceptions of their condition and captures nine dimensions. Physicians completed
      the Revised Illness Perception Questionnaire for Healthcare Professionals which
      consists of seven dimensions and measures perceptions of the healthcare
      professional regarding the disease of their patients. Intraclass correlation was
      performed to examine relationships between pairs of respondents; Cohen's d was
      used for estimating the magnitude of the difference. Results: Questionnaires were
      sent to 284 patients of whom 241 (113 SSc and 128 SLE patients) were included.
      Five rheumatologists and 160 GPs participated. For both diseases, positive
      correlations were found for 'consequences', 'illness coherence' and 'emotional
      representations' among patients, rheumatologists and GPs. GPs scored higher on
      the 'consequences' of these diseases for the patient (d=0.71 for SLE; d=0.80 for
      SSc). Differences between rheumatologists and GPs were small for SSc and moderate
      to large for 'consequences' (d=0.56) and 'timeline acute/chronic' (d=0.95) in SLE
      with higher scores for GPs. Conclusions: For both diseases and among the three
      groups, significant correlations are detected for the dimensions 'consequences',
      'illness coherence' and 'emotional representations'. Differences between
      rheumatologists and GPs were mainly detected in the case of SLE patients. This
      can have implications for the collaboration between these two groups of
      physicians in daily clinical practice. Clinical trial registration: NCT02655640;
      Pre-results.

PMID- 29177062
TI  - Validity of studies suggesting postsurgical chemotherapy for resectable gastric
      cancer: critical appraisal of randomised trials.
AB  - Background and aim: In 2013, Diaz-Nieto et al published a Cochrane review to
      summarise the impact of postsurgical chemotherapy versus surgery alone on
      survival for resectable gastric cancer. The authors concluded that postsurgical
      chemotherapy showed an improvement in overall survival. The aim of this article
      was to assess the validity of four studies included in the Cochrane review and to
      investigate the impact of an exclusion of these four studies on the result of the
      meta-analysis. Methods: Overall survival was selected as endpoint of interest.
      Among the 34 included papers which analysed this endpoint, we identified the four
      publications which have the highest weights to influence the final result. The
      validity of these papers was analysed using the CONSORT (Consolidated Standards
      of Reporting Trials) checklist for randomised controlled trials. We performed a
      new meta-analysis without the four studies in order to assess their impact on the
      general result of the original meta-analysis. Results: The analysed four studies
      revealed several inconsistencies: inappropriate answers were found in up to 77%
      of the items of the CONSORT checklist. Unclear or inadequate randomisation,
      missing blinded set-up, conflict of interest and lacking intention-to-treat
      analysis were the most common findings. When performing a meta-analysis excluding
      the four criticised studies, postsurgical chemotherapy still showed a significant
      improvement in overall survival. Even when excluding all single studies with a
      statistically significant outcome by themselves and performing a meta-analysis on
      the remaining 26 studies, the result remains statistically significant.
      Conclusion: The four most powerful publications in the Cochrane review show
      substantial deficits. We suggest a more critical appraisal regarding the validity
      of single studies. However, after the exclusion of these four studies, the result
      of the meta-analysis did not change.

PMID- 29177063
TI  - Circulating microRNAs as potential biomarkers to detect transformation of
      Barrett's oesophagus to oesophageal adenocarcinoma.
AB  - Objective: Circulating microRNAs (miRNAs) are promising biomarkers for the early
      detection of cancers. This study aimed to address potential circulating miRNAs to
      monitor the progression from Barrett's oesophagus (BO) to oesophageal
      adenocarcinoma (OAC). Design: We comprehensively analysed tissue and serum miRNA
      expression profiles of BO mice model (L2-interleukin-1beta (IL-1beta) mice) using
      microarray analysis. To validate the data from mice, a published dataset of human
      plasma miRNAs, consisting of eight patients with OAC, eight with BO and six
      healthy controls, was used (GSE51410). Results: We identified 20 upregulated
      miRNAs and 44 downregulated miRNAs both in tissues and in sera of 46-week-old
      mice compared with 28-week-old mice. Two of the 20 miRNAs (miR-128-3 p and miR
      328-3 p) were upregulated, and five of the 44 miRNAs (miR-143-3 p, miR-144-3 p,
      miR-15a-5p, miR-1-3 p and miR-133b) were downregulated in plasma of patients with
      OAC compared with plasma of patients with BO. Receiver operating characteristic
      curve analysis revealed that a prediction index calculated by the above-mentioned
      seven miRNAs could discriminate between patients with OAC and those without OAC
      with the area under the curve of 0.91, sensitivity of 1 and specificity of 0.75.
      Conclusions: Levels of the seven circulating miRNAs may represent the tissue
      miRNA levels and could be promising non-invasive biomarkers to evaluate the
      carcinogenic process of BO.

PMID- 29177064
TI  - Efficacy of capsule endoscopy in patients with cirrhosis for the diagnosis of
      upper gastrointestinal lesions and small bowel abnormalities: a study protocol
      for prospective interventional study.
AB  - Introduction and aims: The role of capsule endoscopy (CE) in patients with liver
      cirrhosis (LC) has yet to be established; however, it is likely that it will
      remain a valuable diagnostic modality in several groups of patients with LC. The
      primary aims of the current prospective interventional study are to examine the
      prevalence for small bowel lesions and transit time of CE in the gastrointestinal
      tract in patients with LC with oesophageal varices (EVs) requiring endoscopic
      therapies. Methods and analysis: The current study will be a single-centre
      prospective interventional study. Our study participants are LC subjects with
      portal hypertension who were determined to be necessary for prophylactic
      endoscopic therapies for EVs. From the view point of safety, patients with
      gastrointestinal obstruction or fistula or those being suspected of having
      gastrointestinal obstruction or fistula will be excluded from our study. Patients
      with implanted medical devices will be also excluded. CE will be performed prior
      to prophylactic endoscopic therapies in the same hospitalisation and relevant
      images will be analysed after 8 hours by expert endoscopists. This study will
      continue to recruit until 50 participants. Ethics and dissemination: This study
      has received approval from the Institutional Review Board at Hyogo College of
      Medicine (approval no. 2680). The study protocol, informed assent form and other
      submitted files were reviewed and acknowledged. Final data will be publicly
      scattered regardless of the study results. A report releasing study results will
      be submitted for publication in a suitable journal after being finished in data
      collection. Trial registration number: UMIN000028433
      (https://upload.umin.ac.jp/).

PMID- 29177065
TI  - Patients with symptoms of delayed gastric emptying have a high prevalence of
      oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis.
AB  - Background: Patients with symptoms suggestive of gastroparesis exhibit several
      symptoms, such as epigastric pain, postprandial fullness, bloating and
      regurgitation. It is uncertain if such symptoms reflect underlying oesophageal
      motor disorder. Aims: To examine whether patients with epigastric pain and
      postprandial distress syndrome suggestive of functional dyspepsia and/or
      gastroparesis also have concomitant oesophageal motility abnormalities and, if
      so, whether there are any associations between these disturbances. Methods: In
      this retrospective cohort study, consecutive patients with functional
      gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction
      (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric
      scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring
      using standard protocols. Results: We studied 61 patients with various functional
      upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal
      high-resolution manometry and ambulatory pH monitoring. Forty-four patients
      exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders
      were found in 68% and 42% of patients with or without scintigraphic evidence of
      gastroparesis respectively, suggesting of overlapping gastric and oesophageal
      neuromuscular disorder. Forty-three per cent of patients with gastroparesis had
      abnormal oesophageal acid exposure with mean % pH <4.0 of 7.5 in contrast to 38%
      of those symptomatic controls with normal gastric emptying, with mean %pH <4.0 of
      5.4 (NS). Symptoms of epigastric pain, heartburn/regurgitation, bloating, nausea,
      vomiting, dysphagia, belching and weight loss could not distinguish patients with
      or without gastroparesis, although weight loss was significantly more prevalent
      and severe (p<0.002) in patients with gastroparesis. There was no relationship
      between oesophageal symptoms and motor or pH abnormalities in either groups.
      Conclusions: Irrespective of gastric emptying delay by scintigraphy, patients
      with symptoms suggestive of gastric neuromuscular dysfunction have a high
      prevalence of oesophageal motor disorder and pathological oesophageal acid
      exposure that may contribute to their symptoms and may require therapy. High
      resolution oesophageal manometry and pH monitoring are non-invasive and
      potentially useful in the assessment and management of these patients.

PMID- 29177066
TI  - Non-acid gastro-oesophageal reflux is associated with squamous cell carcinoma of
      the oesophagus.
AB  - Introduction: Squamous cell carcinoma of the oesophagus is a common cancer among
      South Africans. Due to the absence of effective screening and surveillance
      programme for early detection and late presentation, squamous cell carcinoma of
      the oesophagus is usually diagnosed at an advanced stage or when metastasis has
      already occurred. The 5-year survival is often quoted at 5%-10%, which is poor.
      Objectives: To determine the association between oesophageal squamous cell
      carcinoma (OSCC) and non-acid gastro-oesophageal reflux disease. Methods: Study
      design: A cross-sectional case-control analytical study of patients referred to
      the Gastroenterology Division of Steve Biko Academic Hospital in Pretoria, South
      Africa. All patients had combined multichannel impedance and pH studies done and
      interpreted after upper gastroscopy using the American College of
      Gastroenterology guidelines by two clinicians. Results: Thirty-two patients with
      OSCC were recruited: non-acid reflux was found in 23 patients (73%), acid reflux
      in 2 patients (6%) and 7 patients (22%) had normal multichannel impedance and pH
      studies.Forty-nine patients matched by age, gender and race were recruited as a
      control group. Non-acid reflux was found in 11 patients (22%), acid reflux in 31
      patients (63%) and 7 patients (14%) had normal multichannel impedance and pH
      monitoring study. Conclusion: The significance of the association between non
      acid reflux and OSCC was tested using chi2, and simple logistic regression was
      used to adjust for the effects of potential confounders.The OR of developing OSCC
      in patients with non-acid gastro-oesophageal reflux was 8.8 (95% CI 3.2 to 24.5,
      P<0.0001) in this South African group.Alcohol and smoking had no effect on these
      results.

PMID- 29177067
TI  - Joint symptoms associated with anastrozole and letrozole in patients with breast
      cancer: a retrospective comparative study.
AB  - Background: Joint symptoms are a common side effect of aromatase inhibitors.
      However, it is not known if the risk of these symptoms varies between the members
      of this drug class. The aim of this study was to compare the frequency of joint
      symptoms associated with anastrozole and that associated with letrozole. Methods:
      We retrospectively reviewed patients with breast cancer who were treated with
      anastrozole or letrozole at Tsukiji Breast Clinic, Japan, between April 2008 and
      July 2014. Joint symptoms were deemed to include both joint pain and painless
      joint symptoms. The time to onset of joint symptoms in the anastrozole group was
      compared with that in the letrozole group using Kaplan-Meier curves and the log
      rank test. Results: Of 141 patients identified to have received aromatase
      inhibitors, 70 had been treated with anastrozole and 71 with letrozole. Joint
      symptoms occurred in 60.3% of the 141 patients (60.0% in the anastrozole group
      and 60.6% in the letrozole group; p = 1). Median time to appearance of joint
      symptoms was 583 days, with no significant difference between the anastrozole and
      letrozole groups (p = 0.962). There was no significant difference in time to
      onset of joint pain (p = 0.139); however, time to onset of painless joint
      symptoms was significantly shorter in the anastrozole group (p = 0.022). The
      sites at which joint symptoms occurred were similar in the two groups.
      Conclusions: The results of this study indicate that there is no difference in
      the pattern of occurrence of joint symptoms caused by anastrozole and those
      caused by letrozole. Trial registration: Trial registration was not required for
      this study because of its retrospective nature and lack of intervention.

PMID- 29177068
TI  - Carbonate-rich dendrolitic cones: insights into a modern analog for incipient
      microbialite formation, Little Hot Creek, Long Valley Caldera, California.
AB  - Ancient putative microbial structures that appear in the rock record commonly
      serve as evidence of early life on Earth, but the details of their formation
      remain unclear. The study of modern microbial mat structures can help inform the
      properties of their ancient counterparts, but modern mineralizing mat systems
      with morphological similarity to ancient structures are rare. Here, we
      characterize partially lithified microbial mats containing cm-scale dendrolitic
      coniform structures from a geothermal pool ("Cone Pool") at Little Hot Creek,
      California, that if fully lithified, would resemble ancient dendrolitic
      structures known from the rock record. Light and electron microscopy revealed
      that the cm-scale 'dendrolitic cones' were comprised of intertwined microbial
      filaments and grains of calcium carbonate. The degree of mineralization
      (carbonate content) increased with depth in the dendrolitic cones. Sequencing of
      16S rRNA gene libraries revealed that the dendrolitic cone tips were enriched in
      OTUs most closely related to the genera Phormidium, Leptolyngbya, and Leptospira,
      whereas mats at the base and adjacent to the dendrolitic cones were enriched in
      Synechococcus. We hypothesize that the consumption of nutrients during
      autotrophic and heterotrophic growth may promote movement of microbes along
      diffusive nutrient gradients, and thus microbialite growth. Hour-glass shaped
      filamentous structures present in the dendrolitic cones may have formed around
      photosynthetically-produced oxygen bubbles-suggesting that mineralization occurs
      rapidly and on timescales of the lifetime of a bubble. The dendrolitic-conical
      structures in Cone Pool constitute a modern analog of incipient microbialite
      formation by filamentous microbiota that are morphologically distinct from any
      structure described previously. Thus, we provide a new model system to address
      how microbial mats may be preserved over geological timescales.

PMID- 29177069
TI  - Differences in early risk factors for obesity between African American formula
      fed infants and White breastfed controls.
AB  - Background: Previous RCTs to prevent early rapid weight gain were conducted in
      predominantly White, well-educated, middle-income mother-infants at low risk for
      obesity. To inform the design of an RCT in a higher-risk sample, we conducted a
      short-term, longitudinal study to compare maternal feeding beliefs and behaviors,
      infant sleep, intake, and growth of African American formula feeding (AAFF) dyads
      to a comparison sample of White breastfeeding (WBF) dyads. We also assessed the
      feasibility of recruiting and retaining AAFF participants. Methods: AAFF (n = 32)
      and WBF (n = 25) mother-infants were assessed at 2, 8, and 16 weeks postpartum.
      Data included demographics and maternal reports of feeding beliefs and behaviors,
      infant sleep, meal size, and feeding frequency, and measured infant length and
      weight. Results: AAFF and WBF mothers differed in demographics. AAFF mothers
      reported greater agreement with pressuring the infant to eat and feeding to
      soothe a fussy infant. Compared to WBF infants, AAFF infants slept fewer hours
      and consumed more grams/feeding from 2 to 16 weeks. There were no group
      differences in feeding frequency, which resulted in AAFF infants consuming more
      grams/day of milk than WBF infants. AAFF infants had lower gestational age, lower
      weight at 2 weeks, and had more rapid weight gain from 8 to 16 weeks.
      Conclusions: Findings point to potentially modifiable risk factors that may
      underlie disparities in early obesity among AAFF infants, including short sleep
      duration, feeding beliefs and behaviors, and rapid growth, but also confirm the
      challenges of recruiting and retaining AAFF participants, all of which inform the
      design and feasibility of an early preventive intervention. Trial registration:
      Retrospectively registered in clinicaltrials.gov on August 23, 2016 (2013102510).

PMID- 29177070
TI  - Evaluation of neurological changes in secondary progressive multiple sclerosis
      patients treated with immune modulator MIS416: results from a feasibility study.
AB  - Background: While disease progression can be readily monitored in early stage
      relapsing multiple sclerosis (MS), it is more challenging for secondary
      progressive multiple sclerosis (SPMS). This advanced stage of disease has
      distinct pathophysiology due to compartmentalization of neuroinflammatory
      activity within the central nervous system, resulting in increased incidence and
      severity of cognitive dysfunction. The shift in the dominant disease pathways is
      underscored by the failure of relapsing therapies to benefit SPMS patients,
      highlighting the need for novel treatment strategies and clinical trial endpoints
      that are well-aligned with potential benefits. The Expanded Disability Status
      Scale (EDSS) is widely used but is weighted towards ambulatory ability, lacking
      sensitivity to other aspects of neurological impairment experienced in more
      severely disabled SPMS patients, so may not effectively capture their clinical
      status.To investigate the feasibility of an alternative clinical trial endpoint
      model for a phase 2B trial of an immune modulator for SPMS, the potential for
      treatment efficacy-based patient-centered outcomes was assessed within the
      context of a before and after, 12-week clinical trial of safety and tolerability.
      Methods: Patients treated with MIS416 for 12 weeks were evaluated for clinical
      status at baseline and end of dosing, using the established Multiple Sclerosis
      Functional Composite, Short Form Health Survey, and Expanded Disability Status
      Scale. Responder status was determined for eight outcome measures based on
      minimally important change, defined using published studies. To evaluate the
      patients' immune response to MIS416, blood plasma samples collected at baseline
      and pre- and 24-h post doses 1-4 were analyzed using multiplex cytokine
      quantification assays. Results: Using a combination of patient-centered outcomes,
      MIS416 treatment was associated with improved clinical status for 10/11 patients:
      eight patients showed improvement on two to five outcome measures, five of which
      also showed improvement by EDSS. Multi-dimensional scaling analysis of MIS416
      induced factors quantified in individual patients, revealed immune response
      patterns which had a strong concordance with the extent of the patients' clinical
      response. Conclusions: The data support the feasibility of using patient-centered
      outcomes as additional clinical trial endpoints, for determining the efficacy of
      disease-modifying therapies, in secondary progressive multiple sclerosis
      patients. Trial registration: ClinicalTrial.gov, NCT01191996.

PMID- 29177071
TI  - A pilot investigation to optimise methods for a future satiety preload study.
AB  - Background: Preload studies are used to investigate the satiating effects of
      foods and food ingredients. However, the design of preload studies is complex,
      with many methodological considerations influencing appetite responses. The aim
      of this pilot investigation was to determine acceptability, and optimise methods,
      for a future satiety preload study. Specifically, we investigated the effects of
      altering (i) energy intake at a standardised breakfast (gender-specific or non
      gender specific), and (ii) the duration between mid-morning preload and ad
      libitum lunch meal, on morning appetite scores and energy intake at lunch.
      Methods: Participants attended a single study visit. Female participants consumed
      a 214-kcal breakfast (n = 10) or 266-kcal breakfast (n = 10), equivalent to 10%
      of recommended daily energy intakes for females and males, respectively. Male
      participants (n = 20) consumed a 266-kcal breakfast. All participants received a
      250-ml orange juice preload 2 h after breakfast. The impact of different study
      timings was evaluated in male participants, with 10 males following one protocol
      (protocol 1) and 10 males following another (protocol 2). The duration between
      preload and ad libitum lunch meal was 2 h (protocol 1) or 2.5 h (protocol 2),
      with the ad libitum lunch meal provided at 12.00 or 13.00, respectively. All
      female participants followed protocol 2. Visual analogue scale (VAS)
      questionnaires were used to assess appetite responses and food/drink
      palatability. Results: Correlation between male and female appetite scores was
      higher with the provision of a gender-specific breakfast, compared to non-gender
      specific breakfast (Pearson correlation of 0.747 and 0.479, respectively). No
      differences in subjective appetite or ad libitum energy intake were found between
      protocols 1 and 2. VAS mean ratings of liking, enjoyment, and palatability were
      all > 66 out of 100 mm for breakfast, preload, and lunch meals. Conclusions: The
      findings of this pilot study confirm the acceptability of this methodology for
      future satiety preload studies. Appetite scores increased from preload to ad
      libitum lunch meal; however, no specific differences were found between
      protocols. The results highlight the importance of considering energy intake
      prior to preload provision, with a gender-specific breakfast improving the
      correlation between male and female appetite score responses to a morning
      preload.

PMID- 29177072
TI  - Efficacy of platelet-rich plasma injections for symptomatic tendinopathy:
      systematic review and meta-analysis of randomised injection-controlled trials.
AB  - Aim: To determine the efficacy of platelet-rich plasma (PRP) injections for
      symptomatic tendinopathy. Design: Systematic review of randomised, injection
      controlled trials with meta-analysis. Data sources: Systematic searches of
      MEDLINE and EMBASE, supplemented by manual searches. Eligibility criteria for
      selecting studies: Randomised controlled trials with 3 months minimum follow-up
      that evaluated pain reduction with PRP versus control (saline, local anaesthetic,
      corticosteroid) injections in patients with symptomatic tendinopathy. Results: A
      total of 16 randomised controlled trials (18 groups) of PRP versus control were
      included. Median sample size was 35 patients, a study size that would require an
      effect size >=1.0 to achieve statistical significance. PRP was more efficacious
      than control in reducing tendinopathy pain, with an effect size of 0.47 (95% CI
      0.22 to 0.72, p<0.001), signifying a moderate treatment effect. Heterogeneity
      among studies was moderate (I2=67%, p<0.001). In subgroup analysis and meta
      regression, studies with a higher proportion of female patients were associated
      with greater treatment benefits with PRP. Conclusions: Injection of PRP is more
      efficacious than control injections in patients with symptomatic tendinopathy.

PMID- 29177073
TI  - The anticipatory stress response to sport competition; a systematic review with
      meta-analysis of cortisol reactivity.
AB  - Objective: Athletes anticipating sport competition regularly experience distinct
      emotional and physiological responses as a result of the expected psychosocial
      and physical stress. Specifically, cortisol, an indicator of hypothalamic
      pituitary-adrenal axis activation, prepares the athlete for the psychological and
      physiological demands of competition. The objective of this meta-analysis is to
      analyse the magnitude of the anticipatory cortisol response in athletes preparing
      to participate in sport competition and to examine the influence of gender, level
      of competition and data collection time. Design: Systematic review with meta
      analysis. Data sources: Four electronic databases were searched to March 2017:
      PubMed, PsycINFO, SPORTDiscus and Scopus. Eligibility criteria for selecting
      studies: (1) Athletes participating in real sport competition;(2) salivary
      cortisol concentration collected before competition in addition to baseline
      sample(s);(3) original research article published in English language. Results:
      Data from 25 studies provided 27 effect sizes. A significant anticipatory
      cortisol response of g=0.85, p<0.001 was identified. Males had a stronger trend
      for greater cortisol reactivity (g=1.07) than females (g=0.56, p=0.07). Females
      and athletes competing at international level did not demonstrate a significant
      anticipatory stress response. There were no significant differences between level
      of competition, type of sport or time of competition. Meta-regression indicated
      that the anticipatory cortisol response is greater when assessed closer to the
      start of competition (Q=6.85, p=0.009). Summary/conclusion: The anticipatory
      cortisol response before sport competition reflects moderate cortisol reactivity
      that prepares athletes optimally for the demands of sport competition via the
      influence on cognitive processes and attentional control. However, both female
      athletes and international competitors did not demonstrate a significant
      anticipatory cortisol response, possibly due to differences in appraisal of the
      stress of sport competition.

PMID- 29177074
TI  - Prognostic factors for specific lower extremity and spinal musculoskeletal
      injuries identified through medical screening and training load monitoring in
      professional football (soccer): a systematic review.
AB  - Background: Medical screening and load monitoring procedures are commonly used in
      professional football to assess factors perceived to be associated with injury.
      Objectives: To identify prognostic factors (PFs) and models for lower extremity
      and spinal musculoskeletal injuries in professional/elite football players from
      medical screening and training load monitoring processes. Methods: The MEDLINE,
      AMED, EMBASE, CINAHL Plus, SPORTDiscus and PubMed electronic bibliographic
      databases were searched (from inception to January 2017). Prospective and
      retrospective cohort studies of lower extremity and spinal musculoskeletal injury
      incidence in professional/elite football players aged between 16 and 40 years
      were included. The Quality in Prognostic Studies appraisal tool and the modified
      Grading of Recommendations Assessment, Development and Evaluation synthesis
      approach was used to assess the quality of the evidence. Results: Fourteen
      studies were included. 16 specific lower extremity injury outcomes were
      identified. No spinal injury outcomes were identified. Meta-analysis was not
      possible due to heterogeneity and study quality. All evidence related to PFs and
      specific lower extremity injury outcomes was of very low to low quality. On the
      few occasions where multiple studies could be used to compare PFs and outcomes,
      only two factors demonstrated consensus. A history of previous hamstring injuries
      (HSI) and increasing age may be prognostic for future HSI in male players.
      Conclusions: The assumed ability of medical screening tests to predict specific
      musculoskeletal injuries is not supported by the current evidence. Screening
      procedures should currently be considered as benchmarks of function or
      performance only. The prognostic value of load monitoring modalities is unknown.

PMID- 29177075
TI  - Obesity and elevated blood pressure in suburban student athletes.
AB  - Objective: To assess the prevalence of obesity and elevated blood pressure in a
      suburban population of middle school and high school student athletes and examine
      the differences from the previously published populations. Study design: The
      Student Athlete Cardiac Evaluation Registry Study is a single-centre, community
      hospital-based registry study, that provided free annual preparticipation
      physical examinations (PPE) from 2009 to 2017. The PPE on the 906 athletes
      included a history, a physical examination and body metrics including height,
      weight and blood pressure. The blood pressure was measured with an automated
      blood pressure cuff and, if elevated, was remeasured using a manual blood
      pressure cuff with aneroid manometer. The data from the PPE were collected and
      analysed for prevalence of obesity, overweight and elevated blood pressure
      measurements. Results: The prevalence of obesity was 11%, and 19% of participants
      were overweight. Many of the athletes had an elevated blood pressure (15%). There
      was a significant association (P<0.001) between weight and elevated blood
      pressure. Among athletes with elevated blood pressure, 50% were either obese or
      overweight. Conclusions: There was a similar prevalence of overweight athletes in
      our study compared with previously published populations, but there were a lower
      proportion of obese athletes, which may be explained by differences in
      demographics. Despite the differences in study populations and the lower rate of
      obesity, the proportion of athletes with elevated blood pressure in our study was
      similar to prior populations. Weight issues and elevated blood pressure affect
      athletes across a range of different populations.

PMID- 29177076
TI  - Effectiveness and efficiency of different weight machine-based strength training
      programmes for patients with hip or knee osteoarthritis: a protocol for a quasi
      experimental controlled study in the context of health services research.
AB  - Introduction: Osteoarthritis is a chronic musculoskeletal disease with a major
      impact on the individual and the healthcare system. As there is no cure, therapy
      aims for symptom release and reduction of disease progression. Physical exercises
      have been defined as a core treatment for osteoarthritis. However, research
      questions related to dose response, sustainability of effects, economic
      efficiency and safety are still open and will be evaluated in this trial,
      investigating a progressive weight machine-based strength training. Methods and
      analysis: This is a quasi-experimental controlled trial in the context of health
      services research. The intervention group (n=300) is recruited from participants
      of an offer for insurants of a health insurance company suffering from hip or
      knee osteoarthritis. Potential participants of the control group are selected and
      written to from the insurance database according to predefined matching criteria.
      The final statistical twins from the control responders will be determined via
      propensity score matching (n=300). The training intervention comprises 24
      supervised mandatory sessions (2/week) and another 12 facultative sessions
      (1/week). Exercises include resistance training for the lower extremity and core
      muscles by use of weight machines and small training devices. The training offer
      is available at two sites. They differ with respect to the weight machines in use
      resulting in different dosage parameters. Primary outcomes are self-reported pain
      and function immediately after the 12-week intervention period. Health-related
      quality of life, self-efficacy, cost utility and safety will be evaluated as
      secondary outcomes. Secondary analysis will be undertaken with two strata related
      to study site. Participants will be followed up 6, 12 and 24 months after
      baseline. Trial registration number: German Clinical Trial Register DRKS00009257.
      Pre-results.

PMID- 29177077
TI  - Acute pseudogout of the foot following Parathyroidectomy: a case report.
AB  - Background: The current case report is the first in the literature to report the
      association between parathyroidectomy and an episode of probable pseudogout in
      the foot in a patient with diabetes mellitus. Case presentation: The authors
      present a case of pseudogout of the left foot following a subtotal
      parathyroidectomy in an 80-year-old female with type 2 diabetes mellitus and
      primary hyperparathyroidism. Pseudogout, also known as calcium pyrophosphate
      dehydrate deposition disease, is an unusual metabolic sequela following
      parathyroidectomy. Pseudogout attacks have been noted in the immediate post
      operative period following parathyroidectomy, but has rarely been identified in
      the foot. The diagnosis was challenging and there were multiple differential
      diagnoses that were entertained in this case. Conclusions: This case illustrates
      the importance of reviewing the surgical history as there might be a link between
      the previous surgeries and current foot problems. This case also serves as a
      reminder of the importance of calcium and phosphate metabolism in podiatric
      health. Most specifically it demonstrates again the association of pseudogout and
      parathyroidectomy in a patient with diabetes mellitus. Although a rare
      occurrence, it is an important reminder that metabolic imbalances of calcium
      levels can manifest in any bone.

PMID- 29177078
TI  - Which patients presenting with arthralgia eventually develop rheumatoid
      arthritis? The current state of the art.
AB  - Early initiation of treatment in patients with inflammatory arthritis at risk of
      persistence and/or erosive progression is important because it is associated with
      a reduced rate of progression of joint damage and functional disability. It has
      been proposed that a window of opportunity exists, during which disease processes
      are less matured and disease modification can be more effective. The phase of
      arthralgia preceding clinical arthritis is likely to be an important part of this
      window of opportunity, during which treatment might prevent progression to
      clinical arthritis. Several proof-of-concept trials in individuals with
      arthralgia are now evaluating this hypothesis. Central to such trials is the
      ability to identify groups at high risk of rheumatoid arthritis (RA) in whom
      preventive treatment can be tested. This review describes the relevance of
      adequate prediction making, as well as the accuracy of different types of
      predictors (including imaging and serological markers) with their value in
      predicting the progression of arthralgia to arthritis. Despite promising results,
      studies have been performed in heterogeneous patient populations and most
      findings have not been validated in independent studies. Future observational or
      preventive studies should be conducted with homogeneous patient groups (eg,
      patients fulfilling the European League Against Rheumatism criteria for
      arthralgia at risk of RA) in order to increase interstudy comparability and to
      allow result validation.

PMID- 29177079
TI  - Effect of Fcgamma-receptor 3a (FCGR3A) gene polymorphisms on rituximab therapy in
      Hungarian patients with rheumatoid arthritis.
AB  - Background: Rheumatoid arthritis (RA) treatment includes the use of the anti-CD20
      monoclonal antibody rituximab (RTX). RTX acts through Fcgamma-receptors (FCGR) on
      effector natural killer cells and macrophages and it can be administered
      effectively in RA and in lymphomas. Based on the results of in vitro experiments,
      its efficacy may depend of FCGR gene polymorphisms in both diseases. Aim: As
      genetic background of diseases and therapeutic efficacy (pharmacogenetics) may
      vary among different geographical regions, we wished to assess possible
      relationships between FCGR3A polymorphism and the therapeutic outcome of RTX
      therapy in a Hungarian RA cohort. Patients and methods: Altogether, 52 patients,
      6 men and 46 women, were included in the study. Peripheral blood samples were
      used to determine FCGR3A polymorphism by genotyping using real-time PCR method.
      Results: The distribution of FCGR3A genotypes was 8 VV, 34 VF and 10 FF. Disease
      activity score 28 (DAS28) reductions in patients with VV, VF and FF genotypes
      were 1.98+/-0.54 (p=0.008 between DAS28 before and after treatment), 2.07+/-0.23
      (p<0.001) and 1.59+/-0.52 (p=0.014), respectively. Significant differences in
      DAS28 reductions on treatment were found between VF heterozygotes and FF
      homozygotes (p=0.032), as well as between heterozygotes and all (VV+FF)
      homozygotes (p=0.017). Furthermore, significantly more VV (62.5%; p=0.030) and VF
      (64.7%; p=0.015) patients achieved low disease activity compared with FF subjects
      (30.0%). Conclusion: Our results suggest that FCGR3A polymorphism may predict
      more effective disease activity reduction by RTX. Furthermore, carrying the V
      allele may also be associated with better therapeutic response in Hungarian
      patients with RA.

PMID- 29177081
TI  - Impact of gender on the response and tolerance to abatacept in patients with
      rheumatoid arthritis: results from the 'ORA' registry.
AB  - Objective: The impact of gender on the response and tolerance to abatacept was
      assessed in a large prospective cohort during 2 years of follow-up. Methods: From
      the 1017 patients included in the Orencia and Rheumatoid Arthritis registry,
      disease activity was assessed at baseline, 6, 12 and 24 months. The relationship
      between the European League Against Rheumatism (EULAR) response, Disease Activity
      Score 28 (DAS28) remission, rate of adverse events and gender was explored in
      multivariate analysis. Results: 990 patients, 79.3%female, with at least one
      follow-up visit were analysed. At baseline, women had longer disease duration,
      higher disease activity and more often received antitumour necrosis factor (TNF)
      drugs. The remission was not different between men and women during the follow-up
      after adjustment on age, disease duration and activity, rheumatoid factor and
      anti-cyclic citrullinated pyeptide (CCP) positivity, and current disease
      modifying antirheumatic drugs (DMARDs), previous TNF blockers and corticosteroids
      use. The proportion of men and women achieving EULAR good-or-moderate response at
      any endpoints was similar (52.4% vs 55.5%), as well as time to achieving EULAR
      response (5.4+/-4.9 vs 5.6+/-5.2 months). Moderate EULAR response was more
      frequent in women at 6 months (OR=1.80, p=0.02) but was no longer significant at
      12 or 24 months. During the follow-up, the DAS28, the tender joint count score
      and the patient global assessment remained higher in women (p=0.001, 0.04 and
      0.06, respectively). Drug retention and safety were comparable. Conclusion: In
      this large daily practice cohort of established rheumatoid arthritis treated with
      abatacept, women achieved similar remission and EULAR response than men despite
      higher disease activity and tender joint count during the treatment course.

PMID- 29177080
TI  - EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory
      myopathies and their major subgroups: a methodology report.
AB  - Objective: To describe the methodology used to develop new classification
      criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and
      their major subgroups. Methods: An international, multidisciplinary group of
      myositis experts produced a set of 93 potentially relevant variables to be tested
      for inclusion in the criteria. Rheumatology, dermatology, neurology and
      paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26%
      children) and 624 non-IIM comparator cases with mimicking conditions (82% adults,
      18% children). The participating clinicians classified each case as IIM or non
      IIM. Generally, the classification of any given patient was based on few
      variables, leaving remaining variables unmeasured. We investigated the strength
      of the association between all variables and between these and the disease status
      as determined by the physician. We considered three approaches: (1) a probability
      score approach, (2) a sum-of-items approach criteria and (3) a classification
      tree approach. Results: The approaches yielded several candidate models that were
      scrutinised with respect to statistical performance and clinical relevance. The
      probability-score approach showed superior statistical performance and clinical
      practicability and was therefore preferred over the others. We developed a
      classification tree for subclassification of patients with IIM. A calculator for
      electronic devices, such as computers and smartphones, facilitates the use of the
      European League Against Rheumatism/American College of Rheumatology (EULAR/ACR)
      classification criteria. Conclusions: The new EULAR/ACR classification criteria
      provide a patient's probability of having IIM for use in clinical and research
      settings. The probability is based on a score obtained by summing the weights
      associated with a set of criteria items.

PMID- 29177082
TI  - Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially
      important subgroup of diseases.
AB  - At the population level, rheumatoid arthritis (RA) is generally viewed as
      autoimmune in nature with a small subgroup of cases having a palindromic form or
      systemic autoinflammatory disorder (SAID) phenotype. Herein, we describe
      resistant cases of classical autoantibody associated RA that had clinical,
      genetic and therapeutic responses indicative of coexistent autoinflammatory
      disease. Five patients with clinically overlapping features between RA and SAID
      including polysynovitis and autoantibody/shared epitope positivity, and who had
      abrupt severe self-limiting attacks including fevers and serositis, are
      described. Mutations or single nucleotide polymorphisms in recognised
      autoinflammatory pathways were evident. Generally, these cases responded poorly
      to conventional Disease-modifying anti-rheumatic drugs (DMARD) treatment with
      some excellent responses to colchicine or interleukin 1 pathway blockade. A
      subgroup of RA cases have a mixed autoimmune-autoinflammatory phenotype and
      genotype with therapeutic implications.

PMID- 29177083
TI  - Correction: Diffuse idiopathic skeletal hyperostosis (DISH): where we are now and
      where to go next.
AB  - [This corrects the article DOI: 10.1136/rmdopen-2017-000472.][This corrects the
      article DOI: 10.1136/rmdopen-2017-000472.].

PMID- 29177084
TI  - The prisoner's dilemma as a cancer model.
AB  - Tumor development is an evolutionary process in which a heterogeneous population
      of cells with different growth capabilities compete for resources in order to
      gain a proliferative advantage. What are the minimal ingredients needed to
      recreate some of the emergent features of such a developing complex ecosystem?
      What is a tumor doing before we can detect it? We outline a mathematical model,
      driven by a stochastic Moran process, in which cancer cells and healthy cells
      compete for dominance in the population. Each are assigned payoffs according to a
      Prisoner's Dilemma evolutionary game where the healthy cells are the cooperators
      and the cancer cells are the defectors. With point mutational dynamics, heredity,
      and a fitness landscape controlling birth and death rates, natural selection acts
      on the cell population and simulated 'cancer-like' features emerge, such as
      Gompertzian tumor growth driven by heterogeneity, the log-kill law which
      (linearly) relates therapeutic dose density to the (log) probability of cancer
      cell survival, and the Norton-Simon hypothesis which (linearly) relates tumor
      regression rates to tumor growth rates. We highlight the utility, clarity, and
      power that such models provide, despite (and because of) their simplicity and
      built-in assumptions.

PMID- 29177085
TI  - Sucrose modulation of radiofrequency-induced heating rates and cell death.
AB  - Background: Applied radiofrequency (RF) energy induces hyperthermia in tissues,
      facilitating vascular perfusion This study explores the impact of RF radiation on
      the integrity of the luminal endothelium, and then predominately explores the
      impact of altering the conductivity of biologically-relevant solutions on RF
      induced heating rates and cell death. The ability of cells to survive high
      sucrose (i.e. hyperosmotic conditions) to achieve lower conductivity as a
      mechanism for directing hyperthermia is evaluated. Methods: RF radiation was
      generated using a capacitively-coupled radiofrequency system operating at 13.56
      MHz. Temperatures were recorded using a FLIR SC 6000 infrared camera. Results: RF
      radiation reduced cell-to-cell connections among endothelial cells and altered
      cell morphology towards a more rounded appearance at temperatures reported to
      cause in vivo vessel deformation. Isotonic solutions containing high sucrose and
      low levels of NaCl displayed low conductivity and faster heating rates compared
      to high salt solutions. Heating rates were positively correlated with cell death.
      Addition of sucrose to serum similarly reduced conductivity and increased heating
      rates in a dose-dependent manner. Cellular proliferation was normal for cells
      grown in media supplemented with 125 mM sucrose for 24 hours or for cells grown
      in 750 mM sucrose for 10 minutes followed by a 24 h recovery period. Conclusions:
      Sucrose is known to form weak hydrogen bonds in fluids as opposed to ions,
      freeing water molecules to rotate in an oscillating field of electromagnetic
      radiation and contributing to heat induction. The ability of cells to survive
      temporal exposures to hyperosmotic (i.e. elevated sucrose) conditions creates an
      opportunity to use sucrose or other saccharides to selectively elevate heating in
      specific tissues upon exposure to a radiofrequency field.

PMID- 29177086
TI  - Broad-scale redistribution of mRNA abundance and transcriptional machinery in
      response to growth rate in Salmonella enterica serovar Typhimurium.
AB  - We have investigated the connection between the four-dimensional architecture of
      the bacterial nucleoid and the organism's global gene expression programme. By
      localizing the transcription machinery and the transcriptional outputs across the
      genome of the model bacterium Salmonella enterica serovar Typhimurium at
      different stages of the growth cycle, a surprising disconnection between gene
      dosage and transcriptional output was revealed. During exponential growth, gene
      output occurred chiefly in the Ori (origin), Ter (terminus) and NSL (non
      structured left) domains, whereas the Left macrodomain remained transcriptionally
      quiescent at all stages of growth. The apparently high transcriptional output in
      Ter was correlated with an enhanced stability of the RNA expressed there during
      exponential growth, suggesting that longer mRNA half-lives compensate for low
      gene dosage. During exponential growth, RNA polymerase (RNAP) was detected
      everywhere, whereas in stationary phase cells, RNAP was concentrated in the Ter
      macrodomain. The alternative sigma factors RpoE, RpoH and RpoN were not required
      to drive transcription in these growth conditions, consistent with their observed
      binding to regions away from RNAP and regions of active transcription.
      Specifically, these alternative sigma factors were found in the Ter macrodomain
      during exponential growth, whereas they were localized at the Ori macrodomain in
      stationary phase.

PMID- 29177087
TI  - On the (im)possibility of reconstructing plasmids from whole-genome short-read
      sequencing data.
AB  - To benchmark algorithms for automated plasmid sequence reconstruction from short
      read sequencing data, we selected 42 publicly available complete bacterial genome
      sequences spanning 12 genera, containing 148 plasmids. We predicted plasmids from
      short-read data with four programs (PlasmidSPAdes, Recycler, cBar and
      PlasmidFinder) and compared the outcome to the reference sequences. PlasmidSPAdes
      reconstructs plasmids based on coverage differences in the assembly graph. It
      reconstructed most of the reference plasmids (recall=0.82), but approximately a
      quarter of the predicted plasmid contigs were false positives (precision=0.75).
      PlasmidSPAdes merged 84 % of the predictions from genomes with multiple plasmids
      into a single bin. Recycler searches the assembly graph for sub-graphs
      corresponding to circular sequences and correctly predicted small plasmids, but
      failed with long plasmids (recall=0.12, precision=0.30). cBar, which applies
      pentamer frequency analysis to detect plasmid-derived contigs, showed a recall
      and precision of 0.76 and 0.62, respectively. However, cBar categorizes contigs
      as plasmid-derived and does not bin the different plasmids. PlasmidFinder, which
      searches for replicons, had the highest precision (1.0), but was restricted by
      the contents of its database and the contig length obtained from de novo assembly
      (recall=0.36). PlasmidSPAdes and Recycler detected putative small plasmids (<10
      kbp), which were also predicted as plasmids by cBar, but were absent in the
      original assembly. This study shows that it is possible to automatically predict
      small plasmids. Prediction of large plasmids (>50 kbp) containing repeated
      sequences remains challenging and limits the high-throughput analysis of plasmids
      from short-read whole-genome sequencing data.

PMID- 29177088
TI  - Genomic characterization of a local epidemic Pseudomonas aeruginosa reveals
      specific features of the widespread clone ST395.
AB  - Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen with several clones
      being frequently associated with outbreaks in hospital settings. ST395 is among
      these so-called 'international' clones. We aimed here to define the biological
      features that could have helped the implantation and spread of the clone ST395 in
      hospital settings. The complete genome of a multidrug resistant index isolate
      (DHS01) of a large hospital outbreak was analysed. We identified DHS01-specific
      genetic elements, among which were identified those shared with a panel of six
      independent ST395 isolates responsible for outbreaks in other hospitals. DHS01
      has the fifth largest chromosome of the species (7.1 Mbp), with most of its 1555
      accessory genes borne by either genomic islands (GIs, n=48) or integrative and
      conjugative elements (ICEs, n=5). DHS01 is multidrug resistant mostly due to
      chromosomal mutations. It displayed signatures of adaptation to chronic infection
      in part due to the loss of a 131 kbp chromosomal fragment. Four GIs were specific
      to the clone ST395 and contained genes involved in metabolism (GI-4), in
      virulence (GI-6) and in resistance to copper (GI-7). GI-7 harboured an array of
      six copper transporters and was shared with non-pathogenic Pseudomonas sp.
      retrieved from copper-contaminated environments. Copper resistance was confirmed
      phenotypically in all other ST395 isolates and possibly accounted for the
      spreading capability of the clone in hospital outbreaks, where water networks
      have been incriminated. This suggests that genes transferred from copper-polluted
      environments may have favoured the implantation and spread of the international
      clone P. aeruginosa ST395 in hospital settings.

PMID- 29177089
TI  - ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads.
AB  - Antimicrobial resistance (AMR) is one of the major threats to human and animal
      health worldwide, yet few high-throughput tools exist to analyse and predict the
      resistance of a bacterial isolate from sequencing data. Here we present a new
      tool, ARIBA, that identifies AMR-associated genes and single nucleotide
      polymorphisms directly from short reads, and generates detailed and customizable
      output. The accuracy and advantages of ARIBA over other tools are demonstrated on
      three datasets from Gram-positive and Gram-negative bacteria, with ARIBA
      outperforming existing methods.

PMID- 29177090
TI  - Completing bacterial genome assemblies with multiplex MinION sequencing.
AB  - Illumina sequencing platforms have enabled widespread bacterial whole genome
      sequencing. While Illumina data is appropriate for many analyses, its short read
      length limits its ability to resolve genomic structure. This has major
      implications for tracking the spread of mobile genetic elements, including those
      which carry antimicrobial resistance determinants. Fully resolving a bacterial
      genome requires long-read sequencing such as those generated by Oxford Nanopore
      Technologies (ONT) platforms. Here we describe our use of the ONT MinION to
      sequence 12 isolates of Klebsiella pneumoniae on a single flow cell. We assembled
      each genome using a combination of ONT reads and previously available Illumina
      reads, and little to no manual intervention was needed to achieve fully resolved
      assemblies using the Unicycler hybrid assembler. Assembling only ONT reads with
      Canu was less effective, resulting in fewer resolved genomes and higher error
      rates even following error correction with Nanopolish. We demonstrate that
      multiplexed ONT sequencing is a valuable tool for high-throughput bacterial
      genome finishing. Specifically, we advocate the use of Illumina sequencing as a
      first analysis step, followed by ONT reads as needed to resolve genomic
      structure.

PMID- 29177091
TI  - Phylogeographic separation and formation of sexually discrete lineages in a
      global population of Yersinia pseudotuberculosis.
AB  - Yersinia pseudotuberculosis is a Gram-negative intestinal pathogen of humans and
      has been responsible for several nationwide gastrointestinal outbreaks. Large
      scale population genomic studies have been performed on the other human
      pathogenic species of the genus Yersinia, Yersinia pestis and Yersinia
      enterocolitica allowing a high-resolution understanding of the ecology, evolution
      and dissemination of these pathogens. However, to date no purpose-designed large
      scale global population genomic analysis of Y. pseudotuberculosis has been
      performed. Here we present analyses of the genomes of 134 strains of Y.
      pseudotuberculosis isolated from around the world, from multiple ecosystems since
      the 1960s. Our data display a phylogeographic split within the population, with
      an Asian ancestry and subsequent dispersal of successful clonal lineages into
      Europe and the rest of the world. These lineages can be differentiated by CRISPR
      cluster arrays, and we show that the lineages are limited with respect to inter
      lineage genetic exchange. This restriction of genetic exchange maintains the
      discrete lineage structure in the population despite co-existence of lineages for
      thousands of years in multiple countries. Our data highlights how CRISPR can be
      informative of the evolutionary trajectory of bacterial lineages, and merits
      further study across bacteria.

PMID- 29177093
TI  - Patchy promiscuity: machine learning applied to predict the host specificity of
      Salmonella enterica and Escherichia coli.
AB  - Salmonella enterica and Escherichia coli are bacterial species that colonize
      different animal hosts with sub-types that can cause life-threatening infections
      in humans. Source attribution of zoonoses is an important goal for infection
      control as is identification of isolates in reservoir hosts that represent a
      threat to human health. In this study, host specificity and zoonotic potential
      were predicted using machine learning in which Support Vector Machine (SVM)
      classifiers were built based on predicted proteins from whole genome sequences.
      Analysis of over 1000 S.enterica genomes allowed the correct prediction (67 -90 %
      accuracy) of the source host for S. Typhimurium isolates and the same classifier
      could then differentiate the source host for alternative serovars such as S.
      Dublin. A key finding from both phylogeny and SVM methods was that the majority
      of isolates were assigned to host-specific sub-clusters and had high host
      specific SVM scores. Moreover, only a minor subset of isolates had high
      probability scores for multiple hosts, indicating generalists with genetic
      content that may facilitate transition between hosts. The same approach correctly
      identified human versus bovine E. coli isolates (83 % accuracy) and the potential
      of the classifier to predict a zoonotic threat was demonstrated using E. coli
      O157. This research indicates marked host restriction for both S. enterica and E.
      coli, with only limited isolate subsets exhibiting host promiscuity by gene
      content. Machine learning can be successfully applied to interrogate source
      attribution of bacterial isolates and has the capacity to predict zoonotic
      potential.

PMID- 29177092
TI  - Genome-guided identification of novel head-to-tail cyclized antimicrobial
      peptides, exemplified by the discovery of pumilarin.
AB  - The need for novel antibiotics in an era where antimicrobial resistance is on the
      rise, and the number of new approved antimicrobial drugs reaching the market is
      declining, is evident. The underused potential of post-translationally modified
      peptides for clinical use makes this class of peptides interesting candidates. In
      this study, we made use of the vast amounts of available genomic data and
      screened all publicly available prokaryotic genomes (~3000) to identify 394 novel
      head-to-tail cyclized antimicrobial peptides. To verify these in silico results,
      we isolated and characterized a novel antimicrobial peptide from Bacillus pumilus
      that we named pumilarin. Pumilarin was demonstrated to have a circular structure
      and showed antimicrobial activity against several indicator strains, including
      pathogens.

PMID- 29177094
TI  - Safety and immunogenicity of MAGE-A3 cancer immunotherapeutic with dacarbazine in
      patients with MAGE-A3-positive metastatic cutaneous melanoma: an open phase I/II
      study with a first assessment of a predictive gene signature.
AB  - Background: We assessed safety, immunogenicity and clinical activity of
      recombinant MAGE-A3 antigen combined with AS15 immunostimulant (MAGE-A3
      immunotherapeutic) in association with dacarbazine in patients with metastatic
      melanoma. Methods: In this open-label, phase I/II, uncontrolled multicentre trial
      conducted in Belgium and France, patients with MAGE-A3-positive melanoma received
      up to 24 doses of MAGE-A3 immunotherapeutic (four cycles) coadministered with
      eight doses of dacarbazine. Adverse events (AE) were recorded until 31 days
      postvaccination, and serious AEs (SAE), until 30 days following the last dose.
      MAGE-A3-specific antibodies were measured by ELISA. Clinical activity of MAGE-A3
      immunotherapeutic was assessed in patients positive/negative for previously
      identified gene signature (GS) associated with clinical outcome. Results: Forty
      eight patients were enrolled and treated (32 GS+, 15 GS-, 1 unknown GS status);
      two patients completed the study. All patients reported AEs, the most common were
      'general disorders and administration site conditions' (94%). Treatment-related
      AEs were reported by 85% of patients; the most common was pain at injection site
      (38%). Sixteen SAEs were reported by 21% of patients; two were considered as
      treatment related (neutropenia and thrombocytopenia; grade 4). Postdose 4, all
      patients were seropositive for MAGE-A3-specific antibodies, with a geometric mean
      titre of 2778.7 ELISA units (EU)/mL (95% CI 1638.3 to 4712.8). One complete and
      three partial responses were reported (only in GS+ patients). Median overall
      survival was 11.4 months for GS+ and 5.3 months for GS- patients. Conclusion:
      Although this trial shows poor results compared with the new results with
      checkpoint inhibitors, it gives an interesting insight in rapidly developing
      fields like combinations of immunotherapy and chemotherapy, new generation
      vaccines and the use of gene profile as a predictive marker. Trial registration
      number: NCT00849875.

PMID- 29177096
TI  - The 'Charter of Rights for Family Caregivers'. The role and importance of the
      caregiver: an Italian proposal.
AB  - Cancer diagnosis not only shakes the lives of those who are affected, but also
      has impacts on the entire family system, which is involved as if it were itself
      an organism affected by cancer. The oncological illness may cause a breakdown of
      the existing balance in the family system and demands a progressive degree of
      mutual adaptation to family members. The 'VoiNoi' Listening Centre of the Campus
      Bio-Medico University Hospital in Rome has been close to caregivers for several
      years, to support them in the difficult task of providing assistance through
      individual or group psychological support therapy and health education. The
      'Charter of Rights for Family Caregivers' stems from the experience gained over
      the years, with the aim of protecting, supporting and strengthening the role and
      the assistance activity that families carry out in support of their loved ones
      under conditions of fragility.

PMID- 29177095
TI  - Targeting immune checkpoints in breast cancer: an update of early results.
AB  - The immune tumour microenvironment has been shown to play a crucial role in the
      development and progression of cancer. Expression of gene signatures, reflecting
      immune activation, and the presence of tumour-infiltrating lymphocytes were
      associated with favourable outcomes in HER2-positive and triple-negative breast
      cancer. Recently, immunotherapy with immune checkpoint blockade induced long
      lasting responses and improved survival in hard-to-treat malignancies (ie,
      melanoma and non-small cell lung cancer) and are changing treatment paradigms in
      a variety of neoplastic diseases. Immune checkpoint blockade has been evaluated
      in breast cancer, particularly in the triple-negative subtype, with promising
      results observed in monotherapy or in combination with chemotherapy in the
      metastatic and neoadjuvant settings. However, identification of patients who are
      most likely to benefit from immune checkpoint blockade remains challenging, with
      many patients not responding to treatments and a significant financial cost. The
      combination of immune checkpoint blockade with conventional cancer treatments
      such as chemotherapy, radiotherapy, targeted therapies or with other
      immunotherapies is a promising strategy to potentiate its efficacy in breast
      cancer although further research is required to effectively identify who will
      respond to these immunotherapies. In this review we report the most recent
      results that emerged from trials testing immune checkpoint blockade and potential
      predictive biomarkers and emphasise the new strategies that are under clinical
      development in breast cancer.

PMID- 29177097
TI  - Exploration of time points and cut-off values for early tumour shrinkage to
      predict survival outcomes of patients with metastatic colorectal cancer treated
      with first-line chemotherapy using a biexponential model for change in tumour
      size.
AB  - Background: Several studies reported that early tumour shrinkage (ETS) was
      associated with overall survival in patients with metastatic colorectal cancer
      (mCRC) treated with first-line chemotherapy. However, appropriate time point and
      cut-off value for ETS remain unclear because these varied in previous studies.
      Patients and methods: We investigated patients with mCRC who received FOLFOX or
      FOLFIRI with/without molecular-targeted agents as first-line treatment between
      2005 and 2014. Using a biexponential model for change in tumour size, a relative
      change in the sum of the longest diameters of target lesions from baseline was
      estimated at a certain time point in each individual patient. Associations of
      survival outcomes with ETS at various time points based on various cut-off values
      were evaluated by Cox regression analysis with a landmark approach. Results:
      Among the 67 patients reviewed, the objective response rate was 73.1% (95% CI
      62.5% to 83.7%), the median progression-free survival was 10.9 months (95% CI 8.7
      to 13.0 months) and the median overall survival was 25.6 months (95% CI 20.1 to
      27.3 months). The model for change in tumour size agreed with the actual measured
      sizes well. Multivariate Cox regression analysis, including performance status,
      number of metastatic sites and use of targeted agents, showed that ETS at 8 weeks
      based on a cut-off value of 20% was most significantly associated with overall
      survival (HR: 0.404, 95% CI 0.231 to 0.707, P=0.0015). Conclusion: It is
      suggested that a time point of 8 weeks and a cut-off value of 20% may be optimal
      criteria for defining ETS.

PMID- 29177098
TI  - Implementation of the free maternity services policy and its implications for
      health system governance in Kenya.
AB  - Introduction: To move towards universal health coverage, the government of Kenya
      introduced free maternity services in all public health facilities in June 2013.
      User fees are, however, important sources of income for health facilities and
      their removal has implications for the way in which health facilities are
      governed. Objective: To explore how implementation of Kenya's financing policy
      has affected the way in which the rules governing health facilities are made,
      changed, monitored and enforced. Methods: Qualitative research was carried out
      using semistructured interviews with 39 key stakeholders from six counties in
      Kenya: 10 national level policy makers, 10 county level policy makers and 19
      implementers at health facilities. Participants were purposively selected using
      maximum variation sampling. Data analysis was informed by the institutional
      analysis framework, in which governance is defined by the rules that distribute
      roles among key players and shape their actions, decisions and interactions.
      Results: Lack of clarity about the new policy (eg, it was unclear which services
      were free, leading to instances of service user exploitation), weak enforcement
      mechanisms (eg, delayed reimbursement to health facilities, which led to
      continued levying of service charges) and misaligned incentives (eg, the policy
      led to increased uptake of services thereby increasing the workload for health
      workers and health facilities losing control of their ability to generate and
      manage their own resources) led to weak policy implementation, further
      complicated by the concurrent devolution of the health system. Conclusion: The
      findings show the consequences of discrepancies between formal institutions and
      informal arrangements. In introducing new policies, policy makers should ensure
      that corresponding institutional (re)arrangements, enforcement mechanisms and
      incentives are aligned with the objectives of the implementers.

PMID- 29177099
TI  - Estimating the need for inpatient neonatal services: an iterative approach
      employing evidence and expert consensus to guide local policy in Kenya.
AB  - Universal access to quality newborn health services will be essential to meeting
      specific Sustainable Development Goals to reduce neonatal and overall child
      mortality. Data for decision making are crucial for planning services and
      monitoring progress in these endeavours. However, gaps in local population-level
      and facility-based data hinder estimation of health service requirements for
      effective planning in many low-income and middle-income settings. We worked with
      local policy makers and experts in Nairobi City County, an area with a population
      of four million and the highest neonatal mortality rate amongst counties in
      Kenya, to address this gap, and developed a systematic approach to use available
      data to support policy and planning. We developed a framework to identify major
      neonatal conditions likely to require inpatient neonatal care and identified
      estimates of incidence through literature review and expert consultation, to give
      an overall estimate for the year 2017 of the need for inpatient neonatal care,
      taking account of potential comorbidities. Our estimates suggest that almost 1 in
      5 newborns (183/1000 live births) in Nairobi City County may need inpatient care,
      resulting in an estimated 24 161 newborns expected to require care in 2017. Our
      approach has been well received by local experts, who showed a willingness to
      work together and engage in the use of evidence in healthcare planning. The
      process highlighted the need for co-ordinated thinking on admission policy and
      referral care especially in a pluralistic provider environment helping build
      further appetite for data-informed decision making.

PMID- 29177100
TI  - 20 years of gender mainstreaming in health: lessons and reflections for the
      neglected tropical diseases community.
AB  - Neglected tropical diseases (NTDs) affect the poorest of the poor. NTD programmes
      can and should rise to the challenge of playing a part in promoting more gender
      equitable societies. Gender equity shapes poverty and the experience of disease
      in multiple ways; yet to date, there has been little attention paid to gender
      equity in NTD control efforts. Drawing on a synthesis of relevant literature, the
      tacit knowledge and experience of the authors, and discussions at a meeting on
      women, girls and NTDs, this analysis paper distills five key lessons from over 20
      years of gender mainstreaming in health. The paper links this learning to NTDs
      and Mass Drug Administration (MDA). Our first lesson is that tailored gender
      frameworks support gender analysis within research and programming. We present a
      gender review framework focusing on different MDA strategies. Second, gender
      interplays with other axes of inequality, such as disability and geographical
      location; hence, intersectionality is important for inclusive and responsive NTD
      programmes. Third, gender, power and positionality shape who is chosen as
      community drug distributors (CDDs). How CDDs interact with communities and how
      this interface role is valued and practised needs to be better understood.
      Fourth, we need to unpack the gender and power dynamics at household level to
      assess how this impacts MDA coverage and interactions with CDDs. Finally, we need
      to collect and use sex disaggregated data to support the development of more
      equitable and sustainable NTD programmes.

PMID- 29177101
TI  - From blockchain technology to global health equity: can cryptocurrencies finance
      universal health coverage?
AB  - Blockchain technology and cryptocurrencies could remake global health financing
      and usher in an era global health equity and universal health coverage. We
      outline and provide examples for at least four important ways in which this
      potential disruption of traditional global health funding mechanisms could occur:
      universal access to financing through direct transactions without third parties;
      novel new multilateral financing mechanisms; increased security and reduced fraud
      and corruption; and the opportunity for open markets for healthcare data that
      drive discovery and innovation. We see these issues as a paramount to the
      delivery of healthcare worldwide and relevant for payers and providers of
      healthcare at state, national and global levels; for government and non
      governmental organisations; and for global aid organisations, including the WHO,
      International Monetary Fund and World Bank Group.

PMID- 29177102
TI  - Assessment of R18, COG1410, and APP96-110 in Excitotoxicity and Traumatic Brain
      Injury.
AB  - Cationic arginine-rich and poly-arginine peptides (referred to as CARPs) have
      potent neuroprotective properties in in vitro excitotoxicity and in vivo models
      of stroke. Traumatic brain injury (TBI) shares many pathophysiological processes
      as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide,
      poly-arginine R18, with the COG1410 and APP96-110 peptides, which have
      neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic
      acid excitotoxicity injury model, R18 was highly neuroprotective and reduced
      neuronal calcium influx, while COG1410 and APP96-110 displayed modest
      neuroprotection and were less effective at reducing calcium influx. In an impact
      acceleration closed-head injury model (Marmarou model), R18, COG1410, and APP96
      110 were administered intravenously (300 nmol/kg) at 30 minutes after injury in
      male Sprague-Dawley rats. When compared to vehicle, no peptide significantly
      improved functional outcomes, however the R18 and COG1410 treatment groups
      displayed positive trends in the adhesive tape test and rotarod assessments.
      Similarly, no peptide had a significant effect on hippocampal neuronal loss,
      however a significant reduction in axonal injury was observed for R18 and
      COG1410. In conclusion, this study has demonstrated that R18 is significantly
      more effective than COG1410 and APP96-110 at reducing neuronal injury and calcium
      influx following excitotoxicity, and that both R18 and COG1410 reduce axonal
      injury following TBI. Additional dose response and treatment time course studies
      are required to further assess the efficacy of R18 in TBI.

PMID- 29177103
TI  - Postural Control and Emotion in Children with Autism Spectrum Disorders.
AB  - Autism Spectrum Disorders subjects (ASD) are well known to have deficits in
      social interaction. We recorded simultaneously eye movements and postural sway
      during exploration of emotional faces in children with ASD and typically
      developing children (TD). We analyzed several postural and ocular parameters. The
      results showed that all postural parameters were significantly greater in
      children with ASD; ASD made significantly fewer saccades and had shorter fixation
      time than TD, particularly in the eyes, and especially for unpleasant emotions.
      These results suggest that poor postural control of ASD and their impaired visual
      strategies could be due to a lack of interest in social cognition, causing a
      delay in the development of the cortical areas, and thus could have an effect on
      their postural control.

PMID- 29177104
TI  - Environmental proteomics reveals taxonomic and functional changes in an enriched
      aquatic ecosystem.
AB  - Aquatic ecosystem enrichment can lead to distinct and irreversible changes to
      undesirable states. Understanding changes in active microbial community function
      and composition following organic-matter loading in enriched ecosystems can help
      identify biomarkers of such state changes. In a field experiment, we enriched
      replicate aquatic ecosystems in the pitchers of the northern pitcher plant,
      Sarracenia purpurea. Shotgun metaproteomics using a custom metagenomic database
      identified proteins, molecular pathways, and contributing microbial taxa that
      differentiated control ecosystems from those that were enriched. The number of
      microbial taxa contributing to protein expression was comparable between
      treatments; however, taxonomic evenness was higher in controls. Functionally
      active bacterial composition differed significantly among treatments and was more
      divergent in control pitchers than enriched pitchers. Aerobic and facultative
      anaerobic bacteria contributed most to identified proteins in control and
      enriched ecosystems, respectively. The molecular pathways and contributing taxa
      in enriched pitcher ecosystems were similar to those found in larger enriched
      aquatic ecosystems and are consistent with microbial processes occurring at the
      base of detrital food webs. Detectable differences between protein profiles of
      enriched and control ecosystems suggest that a time series of environmental
      proteomics data may identify protein biomarkers of impending state changes to
      enriched states.

PMID- 29177106
TI  - Anti-M Alloimmunization: Management and Outcome at a Single Institution.
AB  - Objective  The objective of this study was to review the management strategies
      and outcomes in gravidas with anti-M alloimmunization over 15 years. Study Design
      Data collected from 195 pregnant patients with anti-M antibodies from July 2000
      through June 2016 were reviewed retrospectively. We analyzed indirect
      antiglobulin test titer results, paternal or fetal/neonatal M antigen status,
      antepartum course, and perinatal outcomes. Results  Anti-M antibodies were found
      in 146 women and 195pregnancies. Among those with positive indirect antiglobulin
      tests, 193 pregnancies had titers at or below 1:4. Only one patient with an
      initial low titer experienced a more than twofold increase to a titer 1:64. Two
      women underwent an amniocentesis and cordocentesis. Ninety-five (73.6%) of the
      129 infants tested were positive for the M antigen. Nine infants required
      phototherapy. There were no cases of hemolytic disease of the fetus or newborn,
      mild or severe. Conclusion  The incidence of severe hemolytic disease of the
      newborn due to anti-M is extremely low. We found no cases in our review of 195
      pregnancies, despite several cases of severe hemolytic disease of the newborn
      reported in the literature. We have created an algorithm for the management of
      anti-M antibodies in pregnancy based on our data and extensive literature review.

PMID- 29177105
TI  - Investigating Molecular Connections of Non-alcoholic Fatty Liver Disease with
      Associated Pathological Conditions in West Virginia for Biomarker Analysis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by a
      steatosis of the liver that may progress to more serious pathological conditions
      including: nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. As the
      prevalence of NAFLD has increased worldwide in recent years, pathophysiology and
      risk factors associated with disease progression of NAFLD are at the focus of
      many studies. NAFLD is related to and shares common serum biomarkers with
      cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), obesity, and
      metabolic syndrome (MetS). West Virginia (WV) is a state with some of the highest
      rates of CVD, obesity and diabetes mellitus. As NAFLD is closely related to these
      diseases, it is of particular interest in WV. Currently there is no cost
      effective, standardized method used clinically to detect NAFLD prior to the onset
      of reversible complications. At this time, the diagnosis of NAFLD is made with
      costly radiologic studies and invasive biopsy. These studies are only diagnostic
      once changes to hepatic tissue have occurred. The diagnosis of NAFLD by
      traditional methods may not allow for successful intervention and may not be
      readily available in areas with already sparse medical resources. In this
      literature review, we identify a list of biomarkers common among CVD, T2DM,
      obesity, MetS and NAFLD. From this research we propose the following biomarkers
      are good candidates for inclusion in a panel of biomarkers for the early
      detection of NAFLD: adiponectin, AST, ALT, apo-B, CK18, CPS1, CRP, FABP-1,
      ferritin, GGT, GRP78, HDL-C, IGF-1, IL-1beta, 6, 8, 10, IRS-2PAI-1, leptin,
      lumican, MDA SREBP-1c and TNF-alpha. Creating and implementing a biomarker panel
      for the early detection and attenuation of NAFLD, prior to the onset of
      irreversible complication would provide maximum benefit and decrease the disease
      burden on the patients and healthcare system of WV.

PMID- 29177107
TI  - Treatment of Morbidly Adherent Placentation Utilizing a Standardized
      Multidisciplinary Approach in the Community Hospital-Private Practice Setting.
AB  - Objective  Morbidly adherent placentation is associated with increased maternal
      morbidity and mortality. Recently, there has been mounting evidence supporting
      the benefits of a standardized multidisciplinary approach at tertiary teaching
      hospitals. Our objective was to estimate the impact of the implementation of a
      similar program at a high-volume private community hospital. Study Design  In
      this retrospective cohort study, we evaluated maternal outcomes in all cases of
      histopathologically confirmed morbidly adherent placentation since the initiation
      of our multidisciplinary program (2012-2016). Our data were compared with the
      previously published outcomes of two large cohorts from tertiary teaching
      hospitals in Utah and Texas. Results  In the 28 cases included for evaluation,
      our group's median estimated blood loss, median packed red blood cells
      transfused, median anesthesia time, median length of stay, or rates of maternal
      morbidity did not statistically differ from the published data in Utah or Texas.
      Conclusion  Our data demonstrate the feasibility and utility of a
      multidisciplinary morbidly adherent placentation program in the private
      practice/community hospital setting with outcomes similar to those at tertiary
      teaching hospitals. Implementation of such program may prove beneficial in remote
      centers, where various factors may prohibit patient travel to a larger center.

PMID- 29177108
TI  - Sex Differences in the Expression of Drug-Metabolizing and Transporter Genes in
      Human Liver.
AB  - Human sex differences in the gene expression of drug metabolizing enzymes and
      transporters (DMETs) introduce differences in drug absorption, distribution,
      metabolism and excretion, possibly affecting drug efficacy and adverse reactions.
      However, existing studies aimed at identifying dimorphic expression differences
      of DMET genes are limited by sample size and the number of genes profiled.
      Focusing on a list of 374 DMET genes, we analyzed a previously published gene
      expression data set consisting of human male (n=234) and female (n=193) liver
      samples, and identified 77 genes showing differential expression due to sex. To
      delineate the biological functionalities and regulatory mechanisms for the
      differentially expressed DMET genes, we conducted a co-expression network
      analysis. Moreover, clinical implications of sex differences in the expression of
      human hepatic DMETs are discussed. This study may contribute to the realization
      of personalized medicine by better understanding the inter-individual differences
      between males and females in drug/xenobiotic responses and human disease
      susceptibilities.

PMID- 29177109
TI  - Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel
      Genes Implicated in Cell Immunity and Neuronal Function.
AB  - Objective: Alzheimer's disease (AD) is a neurodegenerative disorder for which
      more than 20 genetic loci have been implicated to date. However, studies
      demonstrate not all genetic factors have been identified. Therefore, in this
      study we seek to identify additional rare variants and novel genes potentially
      contributing to AD. Methods: Whole exome sequencing was performed on 23 multi
      generational families with an average of eight affected subjects. Exome
      sequencing was filtered for rare, nonsynonymous and loss-of-function variants.
      Alterations predicted to have a functional consequence and located within either
      a previously reported AD gene, a linkage peak (LOD>2), or clustering in the same
      gene across multiple families, were prioritized. Results: Rare variants were
      found in known AD risk genes including AKAP9, CD33, CR1, EPHA1, INPP5D, NME8,
      PSEN1, SORL1, TREM2 and UNC5C. Three families had five variants of interest in
      linkage regions with LOD>2. Genes with segregating alterations in these peaks
      include CD163L1 and CLECL1, two genes that have both been implicated in immunity,
      CTNNA1, which encodes a catenin in the cerebral cortex and MIEF1, a gene that may
      induce mitochondrial dysfunction and has the potential to damage neurons. Four
      genes were identified with alterations in more than one family include PLEKHG5, a
      gene that causes Charcot-Marie-Tooth disease and THBS2, which promotes
      synaptogenesis. Conclusion: Utilizing large families with a heavy burden of
      disease allowed for the identification of rare variants co-segregating with
      disease. Variants were identified in both known AD risk genes and in novel genes.

PMID- 29177110
TI  - Advances in the Understanding and Treatment of Mitochondrial Fatty Acid Oxidation
      Disorders.
AB  - Purpose of review: This review focuses on advances made in the past three years
      with regards to understanding the mitochondrial fatty acid oxidation (FAO)
      pathway, the pathophysiological ramifications of genetic lesions in FAO enzymes,
      and emerging therapies for FAO disorders. Recent findings: FAO has now been
      recognized to play a key energetic role in pulmonary surfactant synthesis, T-cell
      differentiation and memory, and the response of the proximal tubule to kidney
      injury. Patients with FAO disorders may face defects in these cellular systems as
      they age. Aspirin, statins, and nutritional supplements modulate the rate of FAO
      under normal conditions and could be risk factors for triggering symptoms in
      patients with FAO disorders. Patients have been identified with mutations in the
      ACAD9 and ECHS1 genes, which may represent new FAO disorders. New interventions
      for long-chain FAODs are in clinical trials. Finally, post-translational
      modifications that regulate fatty acid oxidation protein activities have been
      characterized that represent important new therapeutic targets. Summary: Recent
      research has led to a deeper understanding of FAO. New therapeutic avenues are
      being pursued that may ultimately cause a paradigm shift for patient care.

PMID- 29177111
TI  - The reanalysis of biogeography of the Asian tree frog, Rhacophorus (Anura:
      Rhacophoridae): geographic shifts and climatic change influenced the dispersal
      process and diversification.
AB  - Rapid uplifts of the Tibetan Plateau and climate change in Asia are thought to
      have profoundly modulated the diversification of most of the species distributed
      throughout Asia. The ranoid tree frog genus Rhacophorus, the largest genus in the
      Rhacophoridae, is widely distributed in Asia and especially speciose in the areas
      south and east of the Tibetan Plateau. Here, we infer phylogenetic relationships
      among species and estimate divergence times, asking whether the spatiotemporal
      characteristics of diversification within Rhacophorus were related to rapid
      uplifts of the Tibetan Plateau and concomitant climate change. Phylogenetic
      analysis recovered distinct lineage structures in Rhacophorus, which indicated a
      clear distribution pattern from Southeast Asia toward East Asia and India.
      Molecular dating suggests that the first split within the genus date back to the
      Middle Oligocene (approx. 30 Ma). The Rhacophorus lineage through time (LTT)
      showed that there were periods of increased speciation rate: 14-12 Ma and 10-4
      Ma. In addition, ancestral area reconstructions supported Southeast Asia as the
      ancestral area of Rhacophorus. According to the results of molecular dating,
      ancestral area reconstructions and LTT we think the geographic shifts, the staged
      rapid rises of the Tibetan Plateau with parallel climatic changes and
      reinforcement of the Asian monsoons (15 Ma, 8 Ma and 4-3 Ma), possibly prompted a
      burst of diversification in Rhacophorus.

PMID- 29177115
TI  - Levels of detail analysis of microwave scattering from human head models for
      brain stroke detection.
AB  - In this paper, we have presented a microwave scattering analysis from multiple
      human head models. This study incorporates different levels of detail in the
      human head models and its effect on microwave scattering phenomenon. Two levels
      of detail are taken into account; (i) Simplified ellipse shaped head model (ii)
      Anatomically realistic head model, implemented using 2-D geometry. In addition,
      heterogenic and frequency-dispersive behavior of the brain tissues has also been
      incorporated in our head models. It is identified during this study that the
      microwave scattering phenomenon changes significantly once the complexity of head
      model is increased by incorporating more details using magnetic resonance imaging
      database. It is also found out that the microwave scattering results match in
      both types of head model (i.e., geometrically simple and anatomically realistic),
      once the measurements are made in the structurally simplified regions. However,
      the results diverge considerably in the complex areas of brain due to the
      arbitrary shape interface of tissue layers in the anatomically realistic head
      model. After incorporating various levels of detail, the solution of subject
      microwave scattering problem and the measurement of transmitted and backscattered
      signals were obtained using finite element method. Mesh convergence analysis was
      also performed to achieve error free results with a minimum number of mesh
      elements and a lesser degree of freedom in the fast computational time. The
      results were promising and the E-Field values converged for both simple and
      complex geometrical models. However, the E-Field difference between both types of
      head model at the same reference point differentiated a lot in terms of
      magnitude. At complex location, a high difference value of 0.04236 V/m was
      measured compared to the simple location, where it turned out to be 0.00197 V/m.
      This study also contributes to provide a comparison analysis between the direct
      and iterative solvers so as to find out the solution of subject microwave
      scattering problem in a minimum computational time along with memory resources
      requirement. It is seen from this study that the microwave imaging may
      effectively be utilized for the detection, localization and differentiation of
      different types of brain stroke. The simulation results verified that the
      microwave imaging can be efficiently exploited to study the significant contrast
      between electric field values of the normal and abnormal brain tissues for the
      investigation of brain anomalies. In the end, a specific absorption rate analysis
      was carried out to compare the ionizing effects of microwave signals to different
      types of head model using a factor of safety for brain tissues. It is also
      suggested after careful study of various inversion methods in practice for
      microwave head imaging, that the contrast source inversion method may be more
      suitable and computationally efficient for such problems.

PMID- 29177113
TI  - PBxplore: a tool to analyze local protein structure and deformability with
      Protein Blocks.
AB  - This paper describes the development and application of a suite of tools, called
      PBxplore, to analyze the dynamics and deformability of protein structures using
      Protein Blocks (PBs). Proteins are highly dynamic macromolecules, and a classical
      way to analyze their inherent flexibility is to perform molecular dynamics
      simulations. The advantage of using small structural prototypes such as PBs is to
      give a good approximation of the local structure of the protein backbone. More
      importantly, by reducing the conformational complexity of protein structures, PBs
      allow analysis of local protein deformability which cannot be done with other
      methods and had been used efficiently in different applications. PBxplore is able
      to process large amounts of data such as those produced by molecular dynamics
      simulations. It produces frequencies, entropy and information logo outputs as
      text and graphics. PBxplore is available at https://github.com/pierrepo/PBxplore
      and is released under the open-source MIT license.

PMID- 29177114
TI  - Uncovering the relationship and mechanisms of Tartary buckwheat (Fagopyrum
      tataricum) and Type II diabetes, hypertension, and hyperlipidemia using a network
      pharmacology approach.
AB  - Background: Tartary buckwheat (TB), a crop rich in protein, dietary fiber, and
      flavonoids, has been reported to have an effect on Type II diabetes (T2D),
      hypertension (HT), and hyperlipidemia (HL). However, limited information is
      available about the relationship between Tartary buckwheat and these three
      diseases. The mechanisms of how TB impacts these diseases are still unclear.
      Methods: In this study, network pharmacology was used to investigate the
      relationship between the herb as well as the diseases and the mechanisms of how
      TB might impact these diseases. Results: A total of 97 putative targets of 20
      compounds found in TB were obtained. Then, an interaction network of 97 putative
      targets for these compounds and known therapeutic targets for the treatment of
      the three diseases was constructed. Based on the constructed network, 28 major
      nodes were identified as the key targets of TB due to their importance in network
      topology. The targets of ATK2, IKBKB, RAF1, CHUK, TNF, JUN, and PRKCA were mainly
      involved in fluid shear stress and the atherosclerosis and PI3K-Akt signaling
      pathways. Finally, molecular docking simulation showed that 174 pairs of chemical
      components and the corresponding key targets had strong binding efficiencies.
      Conclusion: For the first time, a comprehensive systemic approach integrating
      drug target prediction, network analysis, and molecular docking simulation was
      developed to reveal the relationships and mechanisms between the putative targets
      in TB and T2D, HT, and HL.

PMID- 29177112
TI  - Transcriptome sequencing reveals high isoform diversity in the ant Formica
      exsecta.
AB  - Transcriptome resources for social insects have the potential to provide new
      insight into polyphenism, i.e., how divergent phenotypes arise from the same
      genome. Here we present a transcriptome based on paired-end RNA sequencing data
      for the ant Formica exsecta (Formicidae, Hymenoptera). The RNA sequencing
      libraries were constructed from samples of several life stages of both sexes and
      female castes of queens and workers, in order to maximize representation of
      expressed genes. We first compare the performance of common assembly and
      scaffolding software (Trinity, Velvet-Oases, and SOAPdenovo-trans), in producing
      de novo assemblies. Second, we annotate the resulting expressed contigs to the
      currently published genomes of ants, and other insects, including the honeybee,
      to filter genes that have annotation evidence of being true genes. Our pipeline
      resulted in a final assembly of altogether 39,262 mRNA transcripts, with an
      average coverage of >300X, belonging to 17,496 unique genes with annotation in
      the related ant species. From these genes, 536 genes were unique to one caste or
      sex only, highlighting the importance of comprehensive sampling. Our final
      assembly also showed expression of several splice variants in 6,975 genes, and we
      show that accounting for splice variants affects the outcome of downstream
      analyses such as gene ontologies. Our transcriptome provides an outstanding
      resource for future genetic studies on F. exsecta and other ant species, and the
      presented transcriptome assembly can be adapted to any non-model species that has
      genomic resources available from a related taxon.

PMID- 29177116
TI  - The ability of laying pullets to negotiate two ramp designs as measured by bird
      preference and behaviour.
AB  - Background: Laying hens are often kept in barn or free-range systems where they
      must negotiate level changes in the house to access resources. However,
      collisions and resultant keel fractures are commonplace. Producers sometimes add
      ramps to make raised areas more accessible but designs vary and very little
      research has investigated bird preference or behaviour when using different ramp
      designs, or the effect of ramp design on falls and collisions. Methods: Two ramp
      designs were studied in an experimental setting-a ramp made of plastic poultry
      slats (grid ramp, GR) and a ramp made of wooden rungs (ladder ramp, LR). Sixty
      four young female hens were trained to move to a food reward and this was used to
      test their behavioural responses when first negotiating the two different ramps
      during individual tests. Both upward and downward transitions were studied. Ramp
      preference was also tested using a room that replicated a commercial single-tier
      system with both types of ramp available. Birds were placed in this room in
      groups of 16 for three days and their use of the ramps studied. Results: A
      greater percentage of birds successfully completed (reached the reward bowl) on
      the GR than the LR during both upward (58% vs 37%) and downward (83% vs 73%)
      transitions, and a smaller percentage of birds made zero attempts to use the GR
      than the LR (upwards: 13% vs 56%, downwards: 8% vs 26%). When making a downward
      transition, more hesitation behaviours were seen (head orientations, stepping on
      the spot, moving away) for the LR. However, more head orientations were seen for
      the GR during the upward transition. Birds were more likely to abort attempts (an
      attempt began when a bird placed both feet on the ramp) to move up the GR than
      the LR. Birds took longer to negotiate the LR than the GR in both directions, and
      more pauses were seen during a successful upward transition on the LR. Birds were
      more likely to move down the GR by walking/running whereas birds tended to jump
      over the entire LR. More collisions with the food reward bowl were seen for the
      LR. In the group tests, birds preferred to use the GR, with more transitions seen
      at all timepoints. However, in these tests, birds preferred to rest on the LR
      with greater numbers of birds counted on this type of ramp during scan sampling
      at all timepoints. Discussion: Behavioural results suggest that the GR was easier
      for the birds to use than the LR, particularly on the downward transition. The GR
      was also less likely to result in collisions. However, the upward transition may
      be more difficult on the GR for some birds, potentially because of the inability
      to pause on a level surface during the transition. The results suggest that the
      GR was preferred by pullets for moving between a raised area and the ground but
      the LR was preferred for resting.

PMID- 29177117
TI  - Gene and genome-centric analyses of koala and wombat fecal microbiomes point to
      metabolic specialization for Eucalyptus digestion.
AB  - The koala has evolved to become a specialist Eucalyptus herbivore since diverging
      from its closest relative, the wombat, a generalist herbivore. This niche
      adaptation involves, in part, changes in the gut microbiota. The goal of this
      study was to compare koala and wombat fecal microbiomes using metagenomics to
      identify potential differences attributable to dietary specialization. Several
      populations discriminated between the koala and wombat fecal communities, most
      notably S24-7 and Synergistaceae in the koala, and Christensenellaceae and RF39
      in the wombat. As expected for herbivores, both communities contained the genes
      necessary for lignocellulose degradation and urea recycling partitioned and
      redundantly encoded across multiple populations. Secondary metabolism was
      overrepresented in the koala fecal samples, consistent with the need to process
      Eucalyptus secondary metabolites. The Synergistaceae population encodes multiple
      pathways potentially relevant to Eucalyptus compound metabolism, and is predicted
      to be a key player in detoxification of the koala's diet. Notably, characterized
      microbial isolates from the koala gut appear to be minor constituents of this
      habitat, and the metagenomes provide the opportunity for genome-directed
      isolation of more representative populations. Metagenomic analysis of other
      obligate and facultative Eucalyptus folivores will reveal whether putatively
      detoxifying bacteria identified in the koala are shared across these marsupials.

PMID- 29177118
TI  - Development of medical informatics in China over the past 30 years from a
      conference perspective and a Sino-American comparison.
AB  - Background: As the world's second-largest economy, China has launched health
      reforms for the second time and invested significant funding in medical
      informatics (MI) since 2010; however, few studies have been conducted on the
      outcomes of this ambitious cause. Objective: This study analyzed the features of
      major MI meetings held in China and compared them with similar MI conferences in
      the United States, aiming at informing researchers on the outcomes of MI in China
      and the US from the professional conference perspective and encouraging greater
      international cooperation for the advancement of the field of medical informatics
      in China and, ultimately, the promotion of China's health reform. Methods:
      Qualitative and quantitative analyses of four MI meetings in China (i.e., CMIAAS,
      CHINC, CHITEC, and CPMI) and two in the US (i.e., AMIA and HIMSS) were conducted.
      Furthermore, the size, constituent parts and regional allocation of participants,
      topics, and fields of research for each meeting were determined and compared.
      Results: From 1985 to 2016, approximately 45,000 individuals attended the CMIAAS
      and CPMI (academic), CHINC and CHITEC (industry), resulting in 5,085 documented
      articles. In contrast, in 2015, 38,000 and 3,700 individuals, respectively,
      attended the American HIMSS (industry) and AMIA (academic) conferences and
      published 1,926 papers in the latter. Compared to those of HIMSS in 2015, the
      meeting duration of Chinese industry CHITEC was 3 vs. 5 days, the number of
      vendors was 100 vs. 1,500+, the number of sub-forums was 10 vs. 250; while
      compared to those of AMIA, the meeting duration of Chinese CMIAAS was 2 vs. 8
      days, the number of vendors was 5 vs. 65+, the number of sub-forums was 4 vs. 26.
      HIMSS and AMIA were more open, international, and comprehensive in comparison to
      the aforementioned Chinese conferences. Conclusions: The current MI in China can
      be characterized as "hot in industry application, and cold in academic research."
      Taking into consideration the economic scale together with the huge investment in
      MI, conference yield and attendee diversity are still low in China. This study
      demonstrates an urgent necessity to elevate the medical informatics discipline in
      China and to expand research fields in order to maintain pace with the
      development of medical informatics in the US and other countries.

PMID- 29177120
TI  - Morphological convergence in 'river dolphin' skulls.
AB  - Convergent evolution can provide insights into the predictability of, and
      constraints on, the evolution of biodiversity. One striking example of
      convergence is seen in the 'river dolphins'. The four dolphin genera that make up
      the 'river dolphins' (Inia geoffrensis, Pontoporia blainvillei, Platanista
      gangetica and Lipotes vexillifer) do not represent a single monophyletic group,
      despite being very similar in morphology. This has led many to using the 'river
      dolphins' as an example of convergent evolution. We investigate whether the
      skulls of the four 'river dolphin' genera are convergent when compared to other
      toothed dolphin taxa in addition to identifying convergent cranial and mandibular
      features. We use geometric morphometrics to uncover shape variation in the skulls
      of the 'river dolphins' and then apply a number of phylogenetic techniques to
      test for convergence. We find significant convergence in the skull morphology of
      the 'river dolphins'. The four genera seem to have evolved similar skull shapes,
      leading to a convergent morphotype characterised by elongation of skull features.
      The cause of this morphological convergence remains unclear. However, the
      features we uncover as convergent, in particular elongation of the rostrum,
      support hypotheses of shared feeding mode or diet and thus provide the foundation
      for future work into convergence within the Odontoceti.

PMID- 29177121
TI  - Hard targets for a second skeleton: therapeutic horizons for fibrodysplasia
      ossificans progressiva (FOP).

PMID- 29177119
TI  - Diversity of bacterial communities on the facial skin of different age-group Thai
      males.
AB  - Background: Skin microbiome varies from person to person due to a combination of
      various factors, including age, biogeography, sex, cosmetics and genetics. Many
      skin disorders appear to be related to the resident microflora, yet databases of
      facial skin microbiome of many biogeographies, including Thai, are limited.
      Methods: Metagenomics derived B-RISA and 16S rRNA gene sequencing was utilized to
      identify the culture-independent bacterial diversity on Thai male faces (cheek
      and forehead areas). Skin samples were categorized (grouped) into (i) normal
      (teenage.hea) and (ii) acne-prone (teenage.acn) young adults, and normal (iii)
      middle-aged (middle.hea) and (iv) elderly (elderly.hea) adults. Results: The 16S
      rRNA gene sequencing was successful as the sequencing depth had an estimated >98%
      genus coverage of the true community. The major diversity was found between the
      young and elderly adults in both cheek and forehead areas, followed by that
      between normal and acne young adults. Detection of representative characteristics
      indicated that bacteria from the order Rhizobiales, genera Sphingomonas and
      Pseudoalteromonas, distinguished the elderly.hea microbiota, along the clinical
      features of wrinkles and pores. Prediction of the metabolic potential revealed
      reduced metabolic pathways involved in replication and repair, nucleotide
      metabolism and genetic translation in the elderly.hea compared with that in the
      teenage.hea. For young adults, some unique compositions such as abundance of
      Propionibacterium acnes and Staphylococcus epidermidis, with a minor diversity
      between normal and acne skins, were detected. The metabolic potentials of the
      acne vs. normal young adults showed that teenage.acn was low in many cellular
      processes (e.g., cell motility and environmental adaptation), but high in
      carbohydrate metabolism, which could support acne growth. Moreover, comparison
      with the age-matched males from the US (Boulder, Colorado) to gain insight into
      the diversity across national biogeography, revealed differences in the
      distribution pattern of species, although common bacteria were present in both
      biogeographical samples. Furthermore, B-RISA served as a crosscheck result to the
      16S rRNA gene sequencing (i.e., differences between teenage and elderly
      microbiota). Conclusions: This study revealed and compared the microbial
      diversity on different aged Thai male faces, and included analyses for
      representing the bacterial flora, the clinical skin characteristics, and
      comparison with the US age-matched. The results represent the first skin
      microbiota of Thai males, and helps the design of a large-scale skin microbiome
      study of Thais. The findings of the diversity among ages, skin type and national
      biogeography supported the importance of these traits in the skin microbiome and
      in developing a safe and sustainable treatment for acne and aging skin diseases.

PMID- 29177122
TI  - Subject-Specific Biomechanical Modelling of the Oropharynx: Towards Speech
      Production.
AB  - Biomechanical models of the oropharynx are beneficial to treatment planning of
      speech impediments by providing valuable insight into the speech function such as
      motor control. In this paper, we develop a subject-specific model of the
      oropharynx and investigate its utility in speech production. Our approach adapts
      a generic tongue-jaw-hyoid model (Stavness et al. 2011) to fit and track dynamic
      volumetric MRI data of a normal speaker, subsequently coupled to a source-filter
      based acoustic synthesizer. We demonstrate our model's ability to track tongue
      tissue motion, simulate plausible muscle activation patterns, as well as generate
      acoustic results that have comparable spectral features to the associated
      recorded audio. Finally, we propose a method to adjust the spatial resolution of
      our subject-specific tongue model to match the fidelity level of our MRI data and
      speech synthesizer. Our findings suggest that a higher resolution tongue model -
      using similar muscle fibre definition - does not show a significant improvement
      in acoustic performance, for our speech utterance and at this level of fidelity;
      however we believe that our approach enables further refinements of the muscle
      fibres suitable for studying longer speech sequences and finer muscle innervation
      using higher resolution dynamic data.

PMID- 29177123
TI  - Recent Advances in Adhesive Bonding - The Role of Biomolecules, Nanocompounds,
      and Bonding Strategies in Enhancing Resin Bonding to Dental Substrates.
AB  - Purpose of review: To present an overview on the main agents (i.e., biomolecules
      and nanocompounds) and/or strategies currently available to amplify or stabilize
      resin-dentin bonding. Recent findings: According to studies retrieved for full
      text reading (2014-2017), there are currently six major strategies available to
      overcome resin-dentin bond degradation: (i) use of collagen crosslinking agents,
      which may form stable covalent bonds with collagen fibrils, thus strengthening
      the hybrid layer; (ii) use of antioxidants, which may allow further
      polymerization reactions over time; (iii) use of protease inhibitors, which may
      inhibit or inactivate metalloproteinases; (iv) modification of the bonding
      procedure, which may be performed by using the ethanol wet-bonding technique or
      by applying an additional adhesive (hydrophobic) coating, thereby strengthening
      the hybrid layer; (v) laser treatment of the substrate prior to bonding, which
      may cause specific topographic changes in the surface of dental substrates,
      increasing bonding efficacy; and (vi) reinforcement of the resin matrix with
      inorganic fillers and/or remineralizing agents, which may positively enhance
      physico-mechanical properties of the hybrid layer. Summary: With the present
      review, we contributed to the better understanding of adhesion concepts and
      mechanisms of resin-dentin bond degradation, showing the current prospects
      available to solve that problematic. Also, adhesively-bonded restorations may be
      benefited by the use of some biomolecules, nanocompounds or alternative bonding
      strategies in order to minimize bond strength degradation.

PMID- 29177125
TI  - Promoting access to dental care in South London: adult patients' perspectives.
AB  - Objective: To evaluate patients' views on health service initiatives established
      to improve uptake of NHS primary dental care amongst adult patients in a socially
      deprived area, comparing practices with extended and regular contract capacity.
      Study design: Service evaluation and cross-sectional survey. Method:
      Questionnaire survey of patients attending a random sample of dental practices in
      three inner-metropolitan boroughs of south London following initiatives to
      improve access to dental care (across dental practices delivering regular and
      extended contracts for services) exploring attendance patterns and the influence
      and awareness of local initiatives to promote access. Results: Four hundred fifty
      adults across 12 dental practices completed questionnaires: 79% reported
      attending for routine and 21% for urgent care. Patients were most aware of
      banners outside practices, followed by dental advertisements in newspapers.
      Vouchers for free treatments were considered of the highest possible influence,
      followed by vouchers for reduced treatment costs and an emergency out-of-hours
      helpline. Awareness and influence were not aligned, and there was no evidence of
      difference by practice contract type whilst there were differences by age and
      type of attendance. Conclusion: The findings suggest that financial incentives
      and emergency services are considered the most influential initiatives for adult
      patients whose attendance patterns appear to be related to personal circumstances
      rather than merely being influenced by the provision of information.

PMID- 29177124
TI  - Harnessing Apoptotic Cells for Transplantation Tolerance: Current Status and
      Future Perspectives.
AB  - Purpose of review: The use of donor apoptotic cells is an emerging therapy for
      inducing transplantation tolerance. In this review, we will discuss current
      understanding of mechanisms of this approach, as well as crucial aspects
      necessary for successful translation of this approach to clinical
      transplantation. Recent findings: Transplantation tolerance by donor apoptotic
      cells is mediated by their homeostatic interaction with recipient phagocytes, and
      subsequent expansion of suppressor cell populations as well as inhibition of
      effector T cells via deletion and anergy. To ensure their tolerogenicity, it is
      critical to procure non-stressed donor cells, and to induce and arrest their
      apoptosis at the appropriate stage prior to their administration. Equally
      important is the monitoring of dynamics of recipient immunological status, and
      its influences on tolerance efficacy and longevity. Emerging concepts and
      technologies may significantly streamline tolerogen manufacture and delivery of
      this approach, and smooth its transition to clinical application. Summary:
      Hijacking homeostatic clearance of donor apoptotic cells is a promising strategy
      for transplantation tolerance. Timing is now mature for concerted efforts for
      transitioning this strategy to clinical transplantation.

PMID- 29177126
TI  - Migrant female head porters' enrolment in and utilisation and renewal of the
      National Health Insurance Scheme in Kumasi, Ghana.
AB  - Purpose: As a social protection policy, Ghana's National Health Insurance Scheme
      (NHIS) aims to improve access to healthcare, especially for the vulnerable.
      Migrant female head porters (kayayoo), who are part of the informal economic
      workforce, are underscored as an ethnic minority and vulnerable group in Ghana.
      This study aimed to analyse the factors associated with enrolment in and renewal
      and utilisation of the NHIS among migrant female head porters in the Kumasi
      Metropolis. Method: We purposively sampled 392 migrant female head porters in the
      Kejetia, Asafo and Bantama markets. We used a binary logit regression model to
      estimate associations among baseline characteristics, convenience and benefit
      factors and enrolment in and renewal and utilisation of the NHIS. Result: Age and
      income significantly increased the probability of NHIS enrolment, renewal and
      utilisation. Long waiting times at NHIS offices significantly reduced the
      likelihood of renewal, while provision of drugs highly significantly increased
      the tendency for migrant female head porters to enrol in, renew and use the NHIS.
      Consulting and surgery also significantly increased renewal and utilisation of
      the NHIS. Conclusion: Political commitment is imperative for effective
      implementation of the decentralisation policy of the NHIS through the National
      Health Insurance Authority in Kumasi. We argue that retail offices should be well
      equipped with logistic facilities to ensure convenience in NHIS initial enrolment
      and renewal processes by citizenry, and by vulnerable groups in particular.

PMID- 29177127
TI  - Different healthy habits between northern and southern Spanish school children.
AB  - Aim: Healthy habits are influenced by several factors such as geographical
      location. The aims of this study were to describe and compare healthy habits
      within two populations of sixth-grade primary school children (aged 11-12 years)
      from northern and southern Spain. Subjects and methods: A cross-sectional study
      using two representative samples of school children was conducted. Participants
      came from Logrono (n = 329) in the north and Granada (n = 284) in the south of
      Spain. Socio-demographic and anthropometric variables, adherence to the
      Mediterranean diet, aerobic fitness, and healthy lifestyles were recorded.
      Results: Boys reported a higher level of physical activity and aerobic fitness
      than girls (p = 0.000). Southern school children reported significantly higher
      adherence to the Mediterranean diet (?: p = 0.041; ?: p = 0.008), lower aerobic
      fitness (?: p = 0.000; ?: p = 0.042) and hours of nightly sleep (?: p = 0.008, ?:
      p = 0.007) than northern school children. Southern boys also reported lower
      levels of physical activity (p = 0.013). There were slight or moderate
      correlations among all habits measured (physical activity, diet, screen and sleep
      time). Additionally, the physical activity level was inversely related to weight
      status. Overweight and obese northern boys reported less physical activity than
      healthy-weight northern boys (p = 0.020) and overweight and obese southern girls
      reported less physical activity than healthy-weight southern girls (p = 0.024).
      Conclusions: Results showed differences in physical activity, eating and sleep
      habits, and aerobic fitness according to geographical location. The relationships
      found among lifestyle habits indicate the need for health promotion interventions
      nationally and considering the differences discussed here.

PMID- 29177128
TI  - Playground usage and physical activity levels of children based on playground
      spatial features.
AB  - Aim: Being outdoors is one of the strongest correlates of physical activity in
      children. Playgrounds are spaces especially designed to enable and foster
      physical activity in children. This study aimed to analyze the relationship
      between the spatial features of public playgrounds and the usage and physical
      activity levels of children playing in them. Subjects and methods: A
      quantitative, observational study was conducted of ten playgrounds in one
      district of a middle-sized town in Germany. Playground spatial features were
      captured using an audit instrument and the playground manual of the town.
      Playground usage and physical activity levels of children were assessed using a
      modified version of the System for Observing Play and Leisure Activity in Youth.
      Negative binomial models were used to analyze the count data. Results: The number
      of children using the playgrounds and the number of children actively playing in
      them were higher in those with more varied facilities and without naturalness.
      Girls played more actively in playgrounds without multi-purpose areas.
      Cleanliness, esthetics, play facility quality, division of functional areas and
      playground size were not related to any outcome variable. Conclusion: Playground
      spatial features are related to playground usage and activity levels of the
      children in the playgrounds. Playgrounds should offer a wide variety of play
      facilities and provide spaces for diverse play activities to respond to the needs
      of large numbers of different children and to provide activity-friendly areas
      enabling their healthy development.

PMID- 29177130
TI  - Sleep Disordered Breathing and Spinal Cord Injury: Challenges and Opportunities.
AB  - Purpose of review: This paper focuses on the sleep disorders in patients with
      spinal cord injury (SCI/D), particularly mechanism of sleep disordered breathing
      (SDB) and challenges in diagnosis and management. Based on a review of recent
      literatures and studies the paper summarizes some main challenges with respect to
      management of SDB in patients with SCI; and what are the responsible mechanisms
      of disease? What are the barriers in diagnosing and treating SDB using standard
      treatment such as positive airway pressure (CPAP)?. Recent findings: Previous
      studies have shown that most SCI/D patients have SDB with heterogeneity in
      prevalence mainly related to using different definition or methods of diagnosing
      SDB, while recent studies using new definition of SDB based on recommended
      criteria from the American Academy of Sleep Medicine (AASM) and also include the
      data on effect of SCI/D level on prevalence and describe different type of SDB.
      Furthermore, recent data describes simplified method of diagnosing SDB by using a
      combination of home sleep apnea testing and transcutaneous CO2 monitoring.
      Finally, emerging data has been pointing at strong relationship between SDB and
      cardiovascular disease including nocturnal hypertension in patients with SCI/D.
      Summary: The findings indicate that early testing for SDB and associated
      cardiovascular disease in patients with SCI is recommended and could be
      beneficial in reduced the high morbidity and mortality in this group of patients
      with disability. In addition, studies on treatment of other sleep disorders in
      SCI/D are not available to inform clinical decision making. Understanding the
      pathophysiology of sleep disorders in SCI/D is critical for the development of
      new effective therapies. This review provides evidence for best practices;
      highlights new discoveries for the diagnosis and management of sleep disorders in
      SCI/D, and discuss challenges and future directions.

PMID- 29177129
TI  - SLEEP AND CIRCADIAN RHYTHM DISORDERS IN PARKINSON'S DISEASE.
AB  - Purpose of review: Sleep disorders are among the most challenging non-motor
      features of Parkinson's disease (PD) and significantly affect quality of life.
      Research in this field has gained recent interest among clinicians and scientists
      and is rapidly evolving. This review is dedicated to sleep and circadian
      dysfunction associated with PD. Recent findings: Most primary sleep disorders may
      co-exist with PD; majority of these disorders have unique features when expressed
      in the PD population. Summary: We discuss the specific considerations related to
      the common sleep problems in Parkinson's disease including insomnia, rapid eye
      movement sleep behavior disorder, restless legs syndrome, sleep disordered
      breathing, excessive daytime sleepiness and circadian rhythm disorders. Within
      each of these sleep disorders, we present updated definitions, epidemiology,
      etiology, diagnosis, clinical implications and management. Furthermore, areas of
      potential interest for further research are outlined.

PMID- 29177131
TI  - Recent Advances in Intestinal Stem Cells.
AB  - Purpose of review: The intestine is a dynamic organ with rapid stem cell division
      generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover
      maintains the epithelial barrier and homeostasis. Current insights on intestinal
      stem cells (ISCs) and their regulation are discussed here. Recent findings: The
      Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also
      divide symmetrically to extinguish or replace ISCs. Following radiation or
      mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de
      differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and
      myofibroblast cells secrete factors that regulate ISC proliferation. Finally,
      several studies indicate that the microbiome metabolites regulate ISC growth.
      Summary: ISC cells can be plastic and integrate a complexity of
      environmental/niche cues to trigger or suppress proliferation as needed.

PMID- 29177133
TI  - Integrin and FAK Regulation of Human Pluripotent Stem Cells.
AB  - Purpose of review: Human pluripotent stem cells (hPSCs) are anchorage-dependent
      cells that can be cultured on a variety of matrices and express integrins and the
      machinery for integrin signaling. Until recently, there has been limited
      understanding of exactly how integrin signaling regulates pluripotent stem cell
      (PSC) behavior. This review summarizes our knowledge of how integrins and focal
      adhesion kinase (FAK) regulate different aspects of hPSC biology. Recent
      findings: The latest research suggests that mouse and human embryonic stem cells
      utilize similar integrin signaling players but with different biological
      outcomes, reflecting the known developmental difference in their pluripotent
      status. Notably, attachment cues via FAK signaling are crucial for hPSCs survival
      and pluripotency maintenance. FAK may be found cortically but also in the nucleus
      of hPSCs intersecting core pluripotency networks. Summary: Integrins and FAK have
      been consigned to the conventional role of cell adhesion receptor systems in
      PSCs. This review highlights data indicating that they are firmly integrated in
      pluripotency circuits, with implications for both research PSC culture and scale
      up and use in clinical applications.

PMID- 29177134
TI  - Automatic Detection and Quantitative DCE-MRI Scoring of Prostate Cancer
      Aggressiveness.
AB  - Purpose: To develop a robust and clinically applicable automated method for
      analyzing Dynamic Contrast Enhanced (DCE-) MRI of the prostate as a guide for
      targeted biopsies and treatments. Materials and methods: An unsupervised pattern
      recognition (PR) method was used to analyze prostate DCE-MRI from 71 sequential
      radiotherapy patients. Identified regions of interest (ROIs) with increased
      perfusion were assigned either to the peripheral (PZ) or transition zone (TZ).
      Six quantitative features, associated with the washin and washout part of the
      weighted average DCE curve from the ROI, were calculated. The associations
      between the assigned DCE-scores and Gleason Score (GS) were investigated. A
      heatmap of tumor aggressiveness covering the entire prostate was generated and
      validated with histopathology from MRI-ultrasound fused (MRI-US) targeted
      biopsies. Results: The volumes of the PR-identified ROI's were significantly
      correlated with the highest GS from the biopsy session for each patient.
      Following normalization (and only after normalization) with gluteus maximus
      muscle's DCE signal, the quantitative features in PZ were significantly
      correlated with GS. These correlations straightened in subset of patients with
      available MRI-US biopsies when GS from the individual biopsies were used. Area
      under the receiver operating characteristics curve for discrimination between
      indolent vs aggressive cancer for the significant quantitative features reached
      0.88-0.95. When DCE-scores were calculated in normal appearing tissues, the
      features were highly discriminative for cancer vs no cancer both in PZ and TZ.
      The generated heatmap of tumor aggressiveness coincided with the location and GS
      of the MRI-US biopsies. Conclusion: A quantitative approach for DCE-MRI analysis
      was developed. The resultant map of aggressiveness correlated well with tumor
      location and GS and is applicable for integration in radiotherapy/radiology
      imaging software for clinical translation.

PMID- 29177132
TI  - Autologous Cell Seeding in Tracheal Tissue Engineering.
AB  - Purpose of Review: There is no consensus on the best technology to be employed
      for tracheal replacement. One particularly promising approach is based upon
      tissue engineering and involves applying autologous cells to transplantable
      scaffolds. Here, we present the reported pre-clinical and clinical data exploring
      the various options for achieving such seeding. Recent Findings: Various cell
      combinations, delivery strategies, and outcome measures are described.
      Mesenchymal stem cells (MSCs) are the most widely employed cell type in tracheal
      bioengineering. Airway epithelial cell luminal seeding is also widely employed,
      alone or in combination with other cell types. Combinations have thus far shown
      the greatest promise. Chondrocytes may improve mechanical outcomes in pre
      clinical models, but have not been clinically tested. Rapid or pre
      vascularization of scaffolds is an important consideration. Overall, there are
      few published objective measures of post-seeding cell viability, survival, or
      overall efficacy. Summary: There is no clear consensus on the optimal cell
      scaffold combination and mechanisms for seeding. Systematic in vivo work is
      required to assess differences between tracheal grafts seeded with combinations
      of clinically deliverable cell types using objective outcome measures, including
      those for functionality and host immune response.

PMID- 29177136
TI  - Expanding the Toolkit for Studies of Aging.

PMID- 29177135
TI  - Quorum Sensing Down-Regulation Counteracts the Negative Impact of Pseudomonas
      aeruginosa on CFTR Channel Expression, Function and Rescue in Human Airway
      Epithelial Cells.
AB  - The function of cystic fibrosis transmembrane conductance regulator (CFTR)
      channels is crucial in human airways. However unfortunately, chronic Pseudomonas
      aeruginosa infection has been shown to impair CFTR proteins in non-CF airway
      epithelial cells (AEC) and to alter the efficiency of new treatments with CFTR
      modulators designed to correct the basic CFTR default in AEC from cystic fibrosis
      (CF) patients carrying the F508del mutation. Our aim was first to compare the
      effect of laboratory strains, clinical isolates, engineered and natural mutants
      to determine the role of the LasR quorum sensing system in CFTR impairment, and
      second, to test the efficiency of a quorum sensing inhibitor to counteract the
      deleterious impact of P. aeruginosa both on wt-CFTR and on the rescue of F508del
      CFTR by correctors. We first report that exoproducts from either the laboratory
      PAO1 strain or a clinical ?Early? isolate (from an early stage of infection)
      altered CFTR expression, localization and function in AEC expressing wt-CFTR.
      Genetic inactivation of the quorum-sensing LasR in PAO1 (PAO1DeltalasR) or in a
      natural clinical mutant (?Late? CF-adapted clinical isolate) abolished wt-CFTR
      impairment. PAO1 exoproducts also dampened F508del-CFTR rescue by VRT-325 or Vx
      809 correctors in CF cells, whereas PAO1DeltalasR had no impact. Importantly,
      treatment of P. aeruginosa cultures with a quorum sensing inhibitor (HDMF)
      prevented the negative effect of P. aeruginosa exoproducts on wt-CFTR and
      preserved CFTR rescue by correctors in CF AEC. These findings indicate that LasR
      interfering strategies could be of benefits to counteract the deleterious effect
      of P. aeruginosa in infected patients.

PMID- 29177137
TI  - Obesity and obstructive sleep apnea risk among Nigerians.
AB  - Background: The contribution of obesity to obstructive sleep apnea (OSA) is
      poorly described in Nigeria. We aimed to compare OSA risk between obese and
      nonobese adults in urban Nigeria. Materials and Methods: An analytic cross
      sectional study was conducted. Participants were interviewed using the World
      Health Organization Non-Communicable Disease questionnaire. OSA risk assessment
      was performed using the STOP-BANG questionnaire. A total score of >=3 on the STOP
      BANG questionnaire indicated OSA risk, whereas a score >=5 indicated high OSA
      risk. Obesity was defined as body mass index (BMI) >30 kg/m2. Relationship
      between obesity and OSA was tested using chi-square and logistic regression
      models used to control for confounding factors. Results: There were 744
      respondents, with a mean age of 44 (standard deviation 10) years. A total of 206
      [27.7%, 95% confidence interval (CI) 24.46-30.9] respondents were obese (BMI >=30
      kg/m2). A total of 307 (41.3%, 95% CI 37.7-44.9) respondents scored >=3 on the
      STOP-BANG questionnaire, whereas 37 (4.9%, 95% CI 3.6-6.7) scored >=5. More
      number of obese than nonobese [57.8% (119/206) versus 34.9% (188/538)]
      respondents met the criteria for OSA risk (P < 0.001). Similarly, more obese
      persons [10.3% (21/206)] met the criteria for high-risk OSA compared to the
      nonobese [3% (16/538)]; P < 0.001. In logistic regression models adjusted for
      cigarette smoking and alcohol consumption, the odds for OSA risk was 15.76 (95%
      CI 7.44-33.9) in persons with BMI >35 kg/m2 compared to those with a BMI range of
      18.5-24.99. Conclusion: Obesity and OSA may be more prevalent in Nigeria than
      previously predicted. Obesity independently increased OSA risk in this
      population.

PMID- 29177138
TI  - Homology Modeling and Virtual Screening to Discover Potent Inhibitors Targeting
      the Imidazole Glycerophosphate Dehydratase Protein in Staphylococcus xylosus.
AB  - The imidazole glycerophosphate dehydratase (IGPD) protein is a therapeutic target
      for herbicide discovery. It is also regarded as a possible target in
      Staphylococcus xylosus (S. xylosus) for solving mastitis in the dairy cow. The 3D
      structure of IGPD protein is essential for discovering novel inhibitors during
      high-throughput virtual screening. However, to date, the 3D structure of IGPD
      protein of S. xylosus has not been solved. In this study, a series of
      computational techniques including homology modeling, Ramachandran Plots, and
      Verify 3D were performed in order to construct an appropriate 3D model of IGPD
      protein of S. xylosus. Nine hits were identified from 2,500 compounds by docking
      studies. Then, these nine compounds were first tested in vitro in S. xylosus
      biofilm formation using crystal violet staining. One of the potential compounds,
      baicalin was shown to significantly inhibit S. xylosus biofilm formation.
      Finally, the baicalin was further evaluated, which showed better inhibition of
      biofilm formation capability in S. xylosus by scanning electron microscopy.
      Hence, we have predicted the structure of IGPD protein of S. xylosus using
      computational techniques. We further discovered the IGPD protein was targeted by
      baicalin compound which inhibited the biofilm formation in S. xylosus. Our
      findings here would provide implications for the further development of novel
      IGPD inhibitors for the treatment of dairy mastitis.

PMID- 29177139
TI  - High Field In vivo13C Magnetic Resonance Spectroscopy of Brain by Random
      Radiofrequency Heteronuclear Decoupling and Data Undersampling.
AB  - In vivo13C magnetic resonance spectroscopy (MRS) is a unique and effective tool
      for studying dynamic human brain metabolism and the cycling of neurotransmitters.
      One of the major technical challenges for in vivo13C-MRS is the high radio
      frequency (RF) power necessary for heteronuclear decoupling. In the common
      practice of in vivo13C-MRS, alkanyl carbons are detected in the spectra range of
      10-65 ppm. The amplitude of decoupling pulses has to be significantly greater
      than the large one-bond 1H-13C scalar coupling (1JCH = 125-145 Hz). Two main
      proton decoupling methods have been developed: broadband stochastic decoupling
      and coherent composite or adiabatic pulse decoupling (e.g., WALTZ); the latter is
      widely used because of its efficiency and superb performance under inhomogeneous
      B1 field. Because the RF power required for proton decoupling increases
      quadratically with field strength, in vivo13C-MRS using coherent decoupling is
      often limited to lowmagnetic fields [<=4 Tesla (T)] to keep the local and
      averaged specific absorption rate (SAR) under the safety guidelines established
      by the International Electrotechnical Commission (IEC) and the US Food and Drug
      Administration (FDA). Alternately, carboxylic/amide carbons are coupled to
      protons via weak long-range 1H-13C scalar couplings, which can be decoupled using
      low RF power broadband stochastic decoupling. Recently, the carboxylic/amide 13C
      MRS technique using low power random RF heteronuclear decoupling was safely
      applied to human brain studies at 7T. Here, we review the two major decoupling
      methods and the carboxylic/amide 13C-MRS with low power decoupling strategy.
      Further decreases in RF power deposition by frequency-domain windowing and time
      domain random under-sampling are also discussed. Low RF power decoupling opens
      the possibility of performing in vivo13C experiments of human brain at very high
      magnetic fields (such as 11.7T), where signal-to-noise ratio as well as spatial
      and temporal spectral resolution are more favorable than lower fields.

PMID- 29177140
TI  - Trichoscopy of Steroid-Induced Atrophy.
AB  - Intralesional corticosteroid (IL-CS) injections have been used to treat a variety
      of dermatological and nondermatological diseases. Although an important
      therapeutic tool in dermatology, a number of local side effects, including skin
      atrophy, have been reported following IL-CS injections. We recently noticed that
      a subset of patients with steroid-induced atrophy presented with ivory-colored
      areas under trichoscopy. We performed a retrospective analysis of trichoscopic
      images and medical records from patients presenting ivory-colored areas
      associated with atrophic scalp lesions. In this paper, we associate this feature
      with the presence of steroid deposits in the dermis and report additional
      trichoscopic features of steroid-induced atrophy on the scalp, such as prominent
      blood vessels and visualization of hair bulbs.

PMID- 29177141
TI  - A Case of Circumscribed Scalp Morphea with Perineural Lymphocytes on Pathology.
AB  - Scalp morphea presents as a scarring alopecia in en coup du sabre pattern. We
      report an unusual presentation of a round hairless patch of morphea on the
      occipital scalp present for 15 years. The scalp lesion aligned with 2 other
      hyperpigmented lesions of biopsy-proven morphea in the lower back. Pathology of
      horizontal sections from the scalp lesion showed follicular dropout, thickening
      of the collagen bundles, and preserved eccrine and follicular structures. Marked
      lymphocytic perineural infiltrate, a reported clue to the diagnosis of scalp
      morphea, contributed to the diagnosis. This case is unusual due to its rare
      clinical presentation. It also highlights the importance of recognizing
      histopathological clues for the diagnosis of uncommon scalp disorders.

PMID- 29177142
TI  - Highly Resistant Acrodermatitis Continua of Hallopeau and Pustular Psoriasis.

PMID- 29177143
TI  - Congenital Curved Nail of the Fourth Toe Associated with Oral Disorders.
AB  - Congenital curved nail of the fourth toe represents an unusual deformity in which
      the nail of the fourth toe curves in a plantar direction. It is unknown why only
      this toe is affected; however, the initial descriptions suggest that this is a
      mesodermal defect. We describe a case of congenital curved nail of the fourth toe
      associated with bifid uvula. There are only 2 reports mentioning the association
      of this nail abnormality with cleft palate and/or lip. In our patient, there was
      an association with bifid uvula that is considered a minor form of palatine
      fissure. There seems to be an association of congenital curved nail of the fourth
      toe with cleft palate to different degrees; however, the pathogenesis of the
      deformity remains unknown.

PMID- 29177144
TI  - Habit Tic Deformity of Bilateral Thumb and Toenails in a Young Boy: An Unusual
      Occurrence.

PMID- 29177145
TI  - Digital Lichen Striatus: Two Case Reports, One with Onychodystrophy.

PMID- 29177146
TI  - Patchy Frontal Fibrosing Alopecia: Description of an Incomplete Clinical
      Presentation.
AB  - We describe 6 incomplete cases of frontal fibrosing alopecia (FFA). All patients
      were postmenopausal women. Their average age was 60 years; 2 of the women were
      Caucasian, and the remaining 4 women were of a mixed ethnicity. The disease
      duration ranged from 3 to 17 years. The patients' lesions presented as irregular
      alopecic plaques in the frontal and/or temporal regions, with few signs of
      perifollicular inflammation, slow progression, and progressive loss of the vellus
      hair in the frontal area. Loss of the eyebrows, facial hyperpigmentation, and
      loss of the body hair were observed in 3 patients, 1 patient, and 2 patients,
      respectively. Localized pruritus and dysesthesia were reported in 5 patients and
      3 patients, respectively. Dermatoscopic examination indicated the absence of
      viable ostia at the centers and edges of the lesions and the absence of peripilar
      erythema; moreover, peripilar hyperkeratosis was less intense than it would be
      expected in classical cases of lichen planopilaris (LPP) and FFA. Histological
      examination revealed that all cases featured the presence of a perifollicular
      lichenoid infiltrate in the infundibulum and isthmus as well as concentric areas
      of fibrosis. All samples were subjected to direct immunofluorescence (DIF), which
      produced negative results. FFA has been recently diagnosed and is considered a
      subtype of LPP. FFA can present with incomplete clinical manifestations, a
      histology similar to LPP, and negative DIF findings. The correct diagnosis of FFA
      associated lesions is critical for providing appropriate treatment, developing
      prognostic definitions, and excluding other types of scarring and nonscarring
      alopecia. The diagnosis of incomplete FFA is essential to avoid diagnostic and
      therapeutic errors.

PMID- 29177147
TI  - Exogen Hairs in Women with and without Hair Loss.
AB  - Contrary to the classical view of the hair cycle, in which telogen is the resting
      phase that precedes the release of the hair shaft, another phase has been
      introduced, exogen. Exogen is the phase wherein the processes for the release of
      the hair shaft are initiated and successfully executed. Exogen ends when the
      shaft is liberated. Accordingly, human hairs would be preferably released not
      with telogen but with exogen roots. To better understand this somehow
      revolutionary point and what occurs in telogen effluvium (TE) and in androgenetic
      alopecia (AGA), we undertook a morphological study. We examined 25 women of
      comparable age by collecting shedding hairs by the Modified Wash Test under
      stringent diagnostic criteria. Eight patients were "normal", 5 had AGA, 9 TE, and
      3 had a TE+AGA overlap. Hair roots were divided into early telogen, full telogen,
      and exogen. Exogens accounted, in normal women, for 2.6% of all hairs, for 5.2%
      in AGA, for 6.6% in TE, and for 2.3% in TE+AGA, without any significant
      difference. Our exogen prevalence (2.6%) did not vary in patients with AGA and
      TE. Therefore, the pathogenetic role of exogen in AGA and TE seems negligible.

PMID- 29177149
TI  - Basal Cell Carcinoma in a Childhood Cancer Survivor: What Neurosurgeons Should
      Avoid.
AB  - Among childhood cancer survivors (CCSs), non-melanoma skin cancer (NMSC) is the
      most common type of second malignancy. Morbidity related to the development of
      NMSC in this group of patients may be sometimes unpredictable and difficult to
      manage. We present the case of a 49-year-old female who was a CCS and developed
      giant superficial basal cell carcinomas (sBCCs) over the previously irradiated
      field of the scalp. BCC involved the atrophic skin overlying the catheter of the
      peritoneal cerebral shunt that was set there for the management of hydrocephalus.
      Topical treatment with imiquimod 5% resulted in local skin reaction that was
      further complicated with catheter exposure. The patient underwent an emergency
      neurosurgery for reposition of the cerebral shunt. Subsequent treatment with
      imiquimod resulted in complete resolution of sBCC. Given the increased risk for
      the development of BCCs in CCSs, awareness of neurosurgeons is crucial. Avoidance
      of setting the catheter of the cerebral shunt within the radiotherapy field is
      highly recommended, in order to avoid unnecessary future surgeries and subsequent
      morbidity, as in our case.

PMID- 29177148
TI  - Descriptive Epidemiology of Hidradenitis Suppurativa in Greece: A Study of 152
      Cases.
AB  - Background/Objective: Hidradenitis suppurativa (HS) is a chronic, inflammatory
      skin disease that remarkably affects the patients' quality of life. A prospective
      study of 152 HS patients was conducted in order to depict the clinico
      epidemiological characteristics of HS patients in Greece. Materials and Methods:
      From February 2015 to August 2016, 152 patients attended the Hidradenitis
      Suppurativa Outpatient Clinic of our department. The most important clinico
      epidemiological data of the patients were registered. Descriptive statistics and
      an ordered logistic regression analysis were performed. Results: Of the 152
      patients, 60.5% were females. Their median age was 37 years. A total of 26.3% of
      the patients suffered from Hurley stage I, 44.7% from Hurley stage II, and 29.0%
      from Hurley stage III. The median duration of disease was 9 years. The most
      common site of involvement was the groins. The mean Dermatology Life Quality
      Index (DLQI) was higher for Hurley stage III. In multivariable analysis, only the
      body mass index was found to independently predict the disease severity.
      Conclusion: Among the factors examined, the body mass index appears to
      independently predict the disease severity. Quality of life evaluation revealed a
      stronger impact compared to the international experience. To our knowledge, this
      is the first descriptive epidemiological study among HS patients in Greece.

PMID- 29177150
TI  - Cutaneous Lupus Erythematosus Presenting as Frontal Fibrosing Alopecia: Report of
      2 Patients.
AB  - Frontal fibrosing alopecia represents a peculiar condition with a quasi
      symmetrical, marginal scarring alopecia along the frontal and temporal hairline.
      The condition has been associated with further histopathologic and/or clinical
      evidence of lichen planopilaris. Since its emergence with the original report of
      Kossard in 1994, frontal fibrosing alopecia has been recognized to be associated
      with a number of comorbidities, including lupus erythematosus. So far, respective
      case reports and case series have given account of frontal fibrosing alopecia
      with the histopathologic features of lichen planopilaris associated or
      overlapping with lupus erythematosus. In contrast, we present cases of
      histopathologically proven cutaneous lupus erythematosus presenting as frontal
      fibrosing alopecia with a good response to the respective treatment with oral
      hydroxychloroquine and/or intralesional triamcinolone acetonide.

PMID- 29177151
TI  - Blue-White Veil as Novel Dermatoscopic Feature in Discoid Lupus Erythematosus in
      2 African-American Patients.
AB  - Dermoscopic features of discoid lupus erythematosus (DLE) depend on the stage of
      the lesions: active lesions include yellow-brown dots and red dots, whereas
      longstanding inactive lesions show absence of follicular openings, cicatricial
      milky red or white patches, structureless white and brown areas, and thick
      arborizing vessels. Loss of pinpoint white dots, blue-gray dots in a speckled
      pattern, and a peripheral pigmented network have been described on dermoscopy of
      DLE in dark skin. We report a blue-white veil as a novel dermoscopic feature in 2
      cases of biopsy-proven DLE in African-American patients. Dry trichoscopy revealed
      a central white area surrounded by irregular patchy areas of confluent blue and
      brown pigment and an overlying white "ground-glass" hue. This corresponds on
      pathology to the hyperkeratosis overlying interface changes at the dermal
      epidermal junction, with pigment incontinence and melanophages in the papillary
      dermis.

PMID- 29177152
TI  - An Atypical Localized Form of Hidradenitis Suppurativa of the Jawline and Neck
      Mimicking Severe Cystic Acne on Presentation.
AB  - Hidradenitis suppurativa (HS) is a chronic and debilitating suppurative disease
      primarily affecting the axillae, perineum, and inframammary regions, where
      apocrine sweat glands are present. However, HS can occur in atypical locations.
      We present an interesting case of a 40-year-old man who developed chronic painful
      subcutaneous nodules, deep sinus tracts, and abscesses involving the jawline and
      the anterior aspect of the neck as the only parts of the body affected and who
      responded satisfactorily to adalimumab and laser hair removal treatment. This
      case is relevant because it helps clinicians to remember that HS may be isolated
      to atypical locations, such as the anterior aspect of the neck and chin. It also
      supports another possible HS pathogenesis which consists of the occlusion of
      terminal hair follicles rather than being essentially a disorder of the apocrine
      glands.

PMID- 29177153
TI  - Poliosis and Neurofibromatosis Type 1: Two Familiar Cases and Review of the
      Literature.
AB  - Two brothers were referred to our clinic for reevaluation of neurofibromatosis
      type 1 (NF1). Both brothers presented a peculiarity that is not so common in NF1:
      poliosis overlying plexiform neurofibromas on the scalp. Poliosis overlying
      plexiform neurofibromas is rarely reported in the literature. The peculiarity of
      our cases is the familiarity and the presence of poliosis in the same location.

PMID- 29177154
TI  - Syphilitic Alopecia: Case Reports and Trichoscopic Findings.
AB  - There has been a resurgence of syphilis in the last decade. Although alopecia is
      not a common manifestation of the disease, the "moth-eaten" pattern is considered
      patognomonic. However, diffuse hair loss, termed essential alopecia, sometimes
      can be the only sign of syphilis infection and mimic other conditions, such as
      alopecia areata and telogen effluvium. We describe three patients with syphilis
      in whom the pattern of alopecia was not typical. Although clinical,
      histopathological, and trichoscopic examinations may share some similar findings
      with other hair diseases, the inclusion of syphilis in the differential diagnosis
      of hair loss causes is fundamental to a correct screening and diagnosis.

PMID- 29177155
TI  - Novel de novo AVPR2 Variant in a Patient with Congenital Nephrogenic Diabetes
      Insipidus.
AB  - Early diagnosis and treatment of congenital nephrogenic diabetes insipidus (CNDI)
      are essential due to the risk of intellectual disability caused by repeated
      episodes of dehydration and rapid rehydration. Timely genetic testing for disease
      causing variants in the arginine vasopressin receptor 2 (AVPR2) gene is possible
      in at-risk newborns with a known family history of X-linked CNDI. In this study,
      a Swedish male with no family history was diagnosed with CNDI at 6 months of age
      during an episode of gastroenteritis. We analyzed the coding regions of AVPR2 by
      PCR and direct DNA sequencing and identified an 80-bp duplication in exon 2
      (GenBank NM_000054.4; c.800_879dup) in the proband. This variant leads to a
      frameshift and introduces a stop codon four codons downstream (p.Ala294Profs*4).
      The variant gene product either succumbs to nonsense-mediated decay or is
      translated to a truncated nonfunctional vasopressin V2 receptor. This variant was
      absent in four unaffected family members, including his parents, as well as in
      100 alleles from healthy controls, and is thus considered a novel de novo disease
      causing variant. Identification of the disease-causing variant facilitated
      precise diagnosis of CNDI in the proband. Furthermore, it allows future genetic
      counseling in the family. This case study highlights the importance of genetic
      testing in sporadic infant cases with CNDI that can occur due to de novo variants
      in AVPR2 or several generations of female transmission of the disease-causing
      variant.

PMID- 29177156
TI  - Risk Factors for Culling, Sales and Deaths in New Zealand Dairy Goat Herds, 2000
      2009.
AB  - The aim of this study was to identify risk factors for culling, sales and deaths
      in intensively managed dairy goat herds in New Zealand. A data set provided by
      the New Zealand Dairy Goat Cooperative (n = 13,197 does) was analyzed using a Cox
      proportional hazard model. The outcome of interest was length of productive life
      (LPL), defined as the number of days from the date of second kidding to the date
      of removal from the herd or the date on which follow-up was terminated, whichever
      occurred first. Milk solids yield in the first lactation (MSL1) as a predictor of
      LPL was parameterized in the model as a penalized spline term. To account for
      MSL1 violating the proportional hazards assumption of the Cox model, LPL was
      divided into two intervals: T1 (less than or equal to 730 days from the date of
      second kidding) and T2 (greater than 730 days from the date of second kidding).
      MSL1 was then included in the model as a time-dependent covariate. A frailty term
      was included in the model to account for unmeasured, herd-level effects on LPL.
      During T1, the daily hazard of removal for does that produced 80 kg milk solids
      in the first lactation was 0.84 (95% CI 0.58-1.23) times the daily hazard of
      removal for does that produced 30 kg milk solids in the first lactation. During
      T2, the daily hazard of removal for does that produced 80 kg milk solids in the
      first lactation was 1.44 (95% CI 0.79-2.65) times the daily hazard of removal for
      does that produced 30 kg milk solids in the first lactation. We conclude that
      involuntary losses may be avoided if high MSL1 yielding does are preferentially
      managed from 2 years beyond the date of second kidding.

PMID- 29177157
TI  - Odds Ratio or Prevalence Ratio? An Overview of Reported Statistical Methods and
      Appropriateness of Interpretations in Cross-sectional Studies with Dichotomous
      Outcomes in Veterinary Medicine.
AB  - One of the most commonly observational study designs employed in veterinary is
      the cross-sectional study with binary outcomes. To measure an association with
      exposure, the use of prevalence ratios (PR) or odds ratios (OR) are possible. In
      human epidemiology, much has been discussed about the use of the OR exclusively
      for case-control studies and some authors reported that there is no good
      justification for fitting logistic regression when the prevalence of the disease
      is high, in which OR overestimate the PR. Nonetheless, interpretation of OR is
      difficult since confusing between risk and odds can lead to incorrect
      quantitative interpretation of data such as "the risk is X times greater,"
      commonly reported in studies that use OR. The aims of this study were (1) to
      review articles with cross-sectional designs to assess the statistical method
      used and the appropriateness of the interpretation of the estimated measure of
      association and (2) to illustrate the use of alternative statistical methods that
      estimate PR directly. An overview of statistical methods and its interpretation
      using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines was conducted and included a diverse set of peer-reviewed
      journals among the veterinary science field using PubMed as the search engine.
      From each article, the statistical method used and the appropriateness of the
      interpretation of the estimated measure of association were registered.
      Additionally, four alternative models for logistic regression that estimate
      directly PR were tested using our own dataset from a cross-sectional study on
      bovine viral diarrhea virus. The initial search strategy found 62 articles, in
      which 6 articles were excluded and therefore 56 studies were used for the overall
      analysis. The review showed that independent of the level of prevalence reported,
      96% of articles employed logistic regression, thus estimating the OR. Results of
      the multivariate models indicated that logistic regression was the method that
      most overestimated the PR. The findings of this study indicate that although
      there are methods that directly estimate PR, many studies in veterinary science
      do not use these methods and misinterpret the OR estimated by the logistic
      regression.

PMID- 29177158
TI  - Editorial: Alternatives to Antimicrobial Growth Promoters and Their Impact in Gut
      Microbiota, Health and Disease.

PMID- 29177159
TI  - Neuroendocrine Tumors of the Gastrointestinal Tract.

PMID- 29177160
TI  - Neuroendocrine Neoplasms: Dichotomy, Origin and Classifications.
AB  - Neuroendocrine neoplasms (NENs) are heterogeneous tumors with a common phenotype.
      There are two fundamentally different groups of NENs: well-differentiated, low
      proliferating NENs, called neuroendocrine tumors (NETs) or carcinoids, and poorly
      differentiated, highly proliferating NENs, called small- or large-cell
      neuroendocrine carcinomas (NECs). This NEN dichotomy is probably due to an origin
      from different neuroendocrine progenitor cells. The current World Health
      Organization (WHO) classification of gastrointestinal NENs uses the Ki67
      proliferation index to grade NETs as G1 or G2, and NECs as G3. In the pancreas,
      NETs and NECs may overlap in their proliferation index, making the distinction
      between them difficult and leading to therapeutic uncertainties. Therefore, the
      WHO classification of pancreatic NENs (PanNENs) from 2017 introduced a new NET G3
      category. Helpful for the distinction of NETs G3 from NECs is the expression of
      p53 and rb1 that is usually negative in PanNETs. Comparison of the WHO
      classification of digestive system NENs with other NEN classifications reveals
      site-specific differences in terminology and a general lack of grading systems.
      However, all classifications recognize the existence of the two major NEN
      families and provide a general basis for their prognostic and therapeutic
      stratification. A development of a common NEN classification across organs is
      desirable.

PMID- 29177162
TI  - Surgical Treatment of Small Intestinal Neuroendocrine Tumors G1/G2.
AB  - Although the majority of neuroendocrine tumors of the small intestine (siNETs)
      classified as low-grade G1 or G2 show slow local growth, they are frequently
      diagnosed at an advanced stage of metastatic disease. The surgical treatment is
      curative in stages I-III or palliative in stage IV in an attempt to avoid local
      complications of bowel obstruction and ischemia of the small bowel by unremoved
      lymph node metastases. Individualized surgical procedures performed by
      experienced surgeons considering tumor multifocality and the primary extent of
      lymph node metastases along the mesenteric vessels are recommended to remove as
      much tumor volume as possible, while avoiding major complications
      intraoperatively and small bowel syndrome postoperatively.

PMID- 29177161
TI  - Early Gastroenteropancreatic Neuroendocrine Tumors: Endoscopic Therapy and
      Surveillance.
AB  - Neuroendocrine neoplasias (NEN) of the stomach, duodenum, pancreas, appendix, or
      rectum that are <=1 cm in size as well as well-differentiated with World Health
      Organization grade 1 (G1) can be considered 'early' neuroendocrine tumors; they
      have a very good prognosis. Regarding prognosis, neuroendocrine tumors (NET) G1
      must be distinguished from well-differentiated NET G2 and poorly differentiated
      neuroendocrine carcinomas (NEC) G3. NET are increasing, with a rise in the age
      adjusted incidence in the USA by about 700% in the last 40 years. Earlier
      diagnosis of NET is one of the main epidemiological changes of clinically
      detected NEN. The general availability of high-resolution endoscopy and advanced
      radiological imaging techniques has contributed to a shift in the discovery to
      smaller-sized (<=10 mm) gastrointestinal and pancreatic NET and earlier tumor
      stages at diagnosis. Thus, screening colonoscopy is effective in the early
      diagnosis not only of colorectal adenomas and adenocarcinomas but also of rectal
      NET. Endoscopic resection is the treatment of choice in NET G1 of the stomach,
      duodenum (despite gastrinoma), and rectum that are <=10 mm in size, do not
      infiltrate the muscularis propria (T1), and do not show angioinvasion (V0, L0).
      Similarly, histologically proven, early pancreatic NET G1 (<=10 mm) may be
      managed conservatively by regular surveillance. In contrast, small (<=1 cm) NET
      G1 of the jejunum or ileum are not 'early' tumors and have to be resected
      surgically with lymph node dissection.

PMID- 29177163
TI  - Surgical Therapy of Sporadic Pancreatic Neuroendocrine Neoplasias G1/G2.
AB  - Background: Pancreatic neuroendocrine neoplasias (pNENs) are uncommon but
      fascinating tumors with an annual incidence of 1 per 100,000 people. pNENs
      present either as functional tumors, causing specific hormonal syndromes like
      Zollinger-Ellison syndrome (ZES) or organic hyperinsulinism, or as non-functional
      pancreatic tumors (NF-pNENs). The natural history of pNENs is highly variable.
      90% of all insulinomas or small NF- pNENs are readily curable by surgical
      resection. Most other functional and late detected NF-pNENs have a less favorable
      chance for cure. Methods: A systematic review of the literature was performed to
      identify the current state of the art with regard to the key issues of surgery in
      pNEN G1/G2. Results: This article provides a comprehensive review of the current
      literature addressing the current challenges in pNEN surgery. Conclusion:
      Patients with completely resected tumors generally have a good prognosis, and an
      aggressive surgical approach combined with conservative treatment options in
      patients with advanced disease rarely provides cure but often results in long
      term survival.

PMID- 29177164
TI  - Medical Therapy of Gastrointestinal Neuroendocrine Tumors.
AB  - Intestinal neuroendocrine tumors (NETs) constitute a heterogeneous group with
      duodenal, small intestinal, colonic and rectal NETs. They constitute more than
      half of all NETs, with the highest frequencies in the rectum, small intestine,
      and colon. The tumor biology varies with the location of the primary tumor as
      well as with the grade and staging of the tumor. Small intestinal NETs usually
      present low proliferation and are treated in the first line with somatostatin
      analogs according to current guidelines. If progression occurs, one can add
      interferon alpha or change the treatment to everolimus. Peptide receptor
      radionuclide therapy (PRRT) with Lutetium177-DOTATATE can be an option in the
      future after registration of the compound. Rectal tumors are usually small when
      they metastasize; they can be treated with somatostatin analogs but more so with
      PRRT, while another option is of course everolimus. Colonic NETs are more
      aggressive than the rest of intestinal NETs and will be treated with everolimus,
      sometimes in combination with somatostatin analogs based on positive
      scintigraphy. Another option is a cytotoxic agent such as streptozotocin plus 5
      fluorouracil (5-FU) or temozolomide plus capecitabine. The most aggressive
      tumors, i.e. neuroendocrine carcinoma G3, are treated with a platin-based therapy
      plus etoposide; if they present with a lower proliferation, i.e. <50%,
      temozolomide plus capecitabine plus bevacizumab can also be attempted. Duodenal
      NETs are mostly treated similar to pancreatic NETs, either with cytotoxic agents,
      streptozotocin plus 5-FU, or temozolomide plus capecitabine, or with targeted
      agents such as everolimus.

PMID- 29177166
TI  - Neuroendocrine Tumors of the Gastrointestinal Tract.

PMID- 29177165
TI  - Theranostics of Neuroendocrine Tumors.
AB  - Somatostatin receptor positron emission tomography/computed tomography using 68Ga
      labeled somatostatin analogs is the mainstay for the evaluation of receptor
      status in neuroendocrine tumors (NETs). This translates towards better therapy
      options, with increasing evidence of peptide receptor radionuclide therapy (PRRT)
      as the treatment of choice for advanced or progressive NETs. There are benefits
      in progression-free and overall survival as well as a significant improvement in
      clinical condition. In patients with progressive NETs, fractionated, personalized
      PRRT results in good therapeutic responses with no significant severe
      hematological and/or renal toxicity, thus improving quality of life.

PMID- 29177167
TI  - Impact of Body Mass Index on Early Postoperative and Long-Term Outcome after
      Rectal Cancer Surgery.
AB  - Background: The aim of this study was to investigate the impact of obesity and
      underweight onto early postoperative and long-term oncological outcome after
      surgery for rectal cancer. Methods: Data from 2008 until 2011 was gathered by a
      German prospective multicenter observational study. 62 items were reported by the
      physicians in charge, and a consecutive follow-up was performed if the patient
      had signed a consent form. Patients were subclassified into: underweight, normal
      weight, overweight, and obese - using the definitions of the World Health
      Organization. Results: In total, 9,920 patients were included, of whom 2.1% were
      underweight and 19.4% obese. The mean age was 68 years (range 21-99 years).
      Postoperative morbidity (mean 38.0%) was significantly increased in underweight
      and obese patients (p < 0.001). In-hospital mortality was 3.1% on average with no
      significant differences among patient groups (p = 0.176). The 5-year overall
      survival ranged between 36.9 and 61.3% and was worse in underweight and prolonged
      in overweight and obese patients compared to those with normal weight (p < 0.001
      each). While the 5-year disease-free survival was increased in overweight and
      obese patients (p < 0.05 each), the 5-year local recurrence rate showed no
      correlation (p > 0.05 each). Multivariate analysis revealed that advanced age,
      higher ASA scoring, postoperative morbidity, and advanced tumor growth worsened
      the long-term survival independently. Conclusions: Underweight patients had a
      worse early and long-term outcome after rectal cancer surgery. Overweight and
      obesity were associated with a significantly better long-term survival.

PMID- 29177169
TI  - Local Administration of Methylprednisolone Laden Hydrogel Enhances Functional
      Recovery of Transected Sciatic Nerve in Rat.
AB  - Objective: To determine the effects of methylprednisolone-laden hydrogel loaded
      into a chitosan conduit on the functional recovery of peripheral nerve using a
      rat sciatic nerve regeneration model was assessed. Methods: 10-mm sciatic nerve
      defect was bridged using a chitosan conduit (CHIT/CGP-Hydrogel) filled with CGP
      hydrogel. In authograft group (AUTO) a segment of sciatic nerve was transected
      and reimplanted reversely. In methylprednisolone treated group (CHIT/MP) the
      conduit was filled with methylprednisolone-laden CGP-hydrogel. The regenerated
      fibers were studied within 16 weeks after surgery. Results: The behavioral,
      functional and electrophysiological studies confirmed faster recovery of the
      regenerated axons in methylprednisolone treated group compared to CHIT/Hydrogel
      group (p<0.05). The mean ratios of gastrocnemius muscles weight were measured.
      There was statistically significant difference between the muscle weight ratios
      of CHIT/MP and CHIT/Hydrogel groups (p<0.05). Morphometric indices of regenerated
      fibers showed number and diameter of the myelinated fibers were significantly
      higher in CHIT/MP than in CHIT/Hydrogel group. Conclusion: Methylprednisolone
      laden hydrogel when loaded in a chitosan conduit resulted in improvement of
      functional recovery and quantitative morphometric indices of sciatic nerve.

PMID- 29177168
TI  - Le Fort Fractures: A Collective Review.
AB  - Le Fort fractures constitute a pattern of complex facial injury that occurs
      secondary to blunt facial trauma.  The most common mechanisms of injury for these
      fractures, which are frequently associated with drug and alcohol use, include
      motor vehicle collisions, assault, and falls. A thorough search of the world's
      literature following PRISMA guidelines was conducted through PubMed and EBSCO
      databases. Search terms included "Le Fort fracture", "facial", "craniofacial",
      and "intracranial."  Articles were selected based on relevance and examined
      regarding etiology, epidemiology, diagnosis, treatment, complications, and
      outcomes in adults. The analyzed studies were published between 1980 and 2016.
      Initial data search yielded 186 results. The search was narrowed to exclude
      articles lacking in specificity for Le Fort fractures.  Fifty-one articles were
      selected, the majority of which were large case studies, and collectively
      reported that Le Fort fractures are most commonly due to high-velocity MVC and
      that the severity of fracture type sustained occurred with increasing frequency. 
      It was also found that there is a general lack of published Level I, Level II,
      and Level III studies regarding Le Fort fracture management, surgical management,
      and outcomes. The limitation of this study, similar to all PRISMA-guided review
      articles, is the dependence on previously published research and availability of
      references as outlined in our methodology. While mortality rates for Le Fort
      fractures are low, these complex injuries seldom occur in isolation and are
      associated with other severe injuries to the head and neck. Quick and accurate
      diagnosis of Le Fort fractures and associated injuries is crucial to the
      successful management of blunt head trauma.

PMID- 29177170
TI  - Effects of Chitosan-Zinc Oxide Nanocomposite Conduit on Transected Sciatic Nerve:
      An Animal Model Study.
AB  - Objective: To determine the effects of chitosan-zinc oxide nanocomposite conduit
      on transected sciatic nerve in animal model of rat. Methods: Sixty male White
      Wistar rats were used in this study. A 10-mm sciatic nerve defect was bridged
      using a chitosan-zinc oxide nanocomposite conduit (CZON) filled with phosphate
      buffered saline. In chitosan group (CHIT) the chitosan conduit was filled with
      phosphate buffered saline solution. In sham-operated group (SHAM), sciatic nerve
      was exposed and manipulated. In transected group (TC), left sciatic nerve was
      transected and nerve cut ends were fixed in the adjacent muscle. The regenerated
      fibers were studied within 12 weeks after surgery. Results: The behavioral and
      functional tests confirmed faster recovery of the regenerated axons in CZON group
      compared to Chitosan group (p<0.05). The mean ratios of gastrocnemius muscles
      weight were measured. There was statistically significant difference between the
      muscle weight ratios of CZON and Chitosan groups (p<0.05). Morphometric indices
      of regenerated fibers showed number and diameter of the myelinated fibers were
      significantly higher in CZON than in Chitosan. In immuohistochemistry, the
      location of reactions to S-100 in CZON was clearly more positive than Chitosan
      group. Conclusion: Chitosan-zinc oxide nanocomposite conduit resulted in
      acceleration of functional recovery and quantitative morphometric indices of
      sciatic nerve.

PMID- 29177172
TI  - Outcome of Long Standing Ulno-Humeral Dislocation Managed by Open Reduction and
      Stabilization with V-Y Plasty; Our Experience.
AB  - Objective: To assess the outcome of long standing ulno-humeral dislocation
      managed by open reduction and stabilization with V-Y plasty. Methods: This cross
      sectional study included 14 patients with elbow dislocation that was more than 3
      months without joint ankylosis, myositis ossificans or nerve injury. The surgical
      management not only included open reduction of the elbow joint, but also
      elongation of the triceps aponeurosis, collateral ligament repair along with the
      stabilization of the elbow joint. The results were analyzed using the Mayo Elbow
      score and the range of motion at 3 months and results were compared with the
      function of the patients elbows before surgery. Results: Among the 14 included
      patients, there were 9 men and 5 women. The mean age of the patients was 27.8+/
      8.3 years. The average ROM Increased from 37.0?+/-25.8? to 99.7?+/-23.3? of
      flexion in the postop followup. Whereas the extension lag changed from 15.5?+/
      14.6? to 19.6?+/-18.3? . The mean Mayo score increased from 47 in the preop
      period to 87 in the postop period. Conclusion: This results demonstrates that
      relative good function with a pretty low risk can be obtained when comparing the
      functional results after 3 months with preoperative status. Based on these
      results we recommend that neglected elbow dislocation should be managed by
      surgical intervention even if the dislocations are old.

PMID- 29177171
TI  - Grafting with Cryopreserved Amniotic Membrane versus Conservative Wound Care in
      Treatment of Pressure Ulcers: A Randomized Clinical Trial.
AB  - Objective: To compare the healing process of pressure ulcers treated with
      cryopreserved human amniotic membrane allograft and routine pressure ulcer care
      in our hospital. Methods: From January 2012 to December 2013, in a prospective
      randomized clinical trial (IRCT201612041335N2), 24 patients with second and third
      stage of pressure ulcers were enrolled in this study. All patients needed split
      thickness skin grafts for pressure ulcer-wound coverage. Selected patients had
      symmetric ulcers on both upper and lower extremities. The patients were randomly
      divided into two groups: amnion and control. In the amnion group, the ulcer was
      covered with cryopreserved amniotic membrane and in the control group it was
      treated with local Dilantin powder application. The duration and success rate of
      complete healing was compared between the two groups. Results: The study group
      was composed of 24 pressure ulcers in 24 patients (19 males and 5 females) with a
      mean age of 44+/-12.70 years. The demographic characteristics, ulcer area, and
      underlying diseases were similar in both groups. The early sign of response, such
      as decrease in wound discharge, was detected 12-14 days after biological
      dressing. Complete pressure ulcer healing occurred only in the amnion group (p<
      0.001). Partial healing was significantly higher in the amnion group (p< 0.03).
      Healing time in this group was faster than that the control group (20 days versus
      54 days). No major complication was recorded with amniotic membrane dressing.
      Conclusion: Cryopreserved amniotic membrane is an effective biologic dressing
      that promotes re-epithelialization in pressure ulcers.

PMID- 29177173
TI  - Functional Outcome of Resection versus Reconstruction in Mason II-III Radial Head
      Fractures; A Short-Term Prospective Study.
AB  - Objective: To compare the short-term functional outcome between resection and
      reconstruction in Mason Type II and Type III radial head fractures using Broberg
      and Morrey score. Methods: A prospective cohort study was conducted in the
      Department of Orthopedic Surgery of SMS Medical College and attached Hospitals. A
      total of 29 patients (15 in resection group, 14 in reconstruction group) between
      the age group of 20-60 years with Mason Type II and Type III fresh closed radial
      head fractures were included in the study. The functional outcome including the
      range of motion, extension lag and Broberg Morrey score were determined and
      compared between two groups. Results: The mean age of resection group was 44.5 +/
      6.6 years and mean age of reconstruction group was 37.1 +/- 6.2 years. The
      baseline characteristics . At 12-months follow-up, in Mason type II fracture,
      radial head reconstruction group with mean extension lag of 9.4 +/- 4.1 and mean
      Broberg Morrey score of 94.9 +/- 5.1 showed better results compared to radial
      head resection group with mean extension lag of 15.7 +/- 4.1 (p=0.022) and mean
      Broberg Morrey score 88.3 +/- 5.1 (p=0.045) respectively. In Mason type III
      fractures, radial head resection with mean supination of 79.4 +/- 4.7, mean
      pronation of 74.4 +/- 4.1 and mean Broberg Morrey score of 89.8 +/- 6 showed
      better results when compared with radial head reconstruction group with mean
      supination of 64.2 +/- 4 (p<0.001), mean pronation of 59.2 +/- 8.4 (p=0.003) and
      mean Broberg Morrey score of 81.9 +/- 5 (p=0.031). Conclusion: The procedure
      suggested in Mason type II, is reconstruction of radial head. In Mason type III
      due to difficulty in achieving anatomical reduction results were not good with
      reconstruction when compared with resection. We recommend radial head excision in
      Mason type III fractures where anatomical and stable fixation is not possible.

PMID- 29177174
TI  - Epidemiology and Outcome Determinants of Pedestrian Injuries in a Level I Trauma
      Center in Southern Iran; A Cross-Sectional Study.
AB  - Objective: To epidemiologically assess the accidents and incidents in the injured
      pedestrians referred to Shahid Rajaee Hospital, Shiraz in order to provide basic
      preventive strategies and reduce injuries and fatalities caused by traffic
      accidents in pedestrians. Methods: This cross-sectional study was conducted on
      5840 injured pedestrians referred to Shahid Rajaee Hospital, Shiraz from 2009 to
      2014. The baseline characteristic including the demographic and clinical
      information, the mechanism of injury, injury severity score (ISS) and outcome
      determinants. We also recorded the outcome measures and the mortality.
      Multivariate logistic regression analysis was performed to investigate the
      factors related to mortality rate and Length of Stay (LOS) in hospital. Results:
      In our study, the history of 5840 injured pedestrians was analyzed. The mean age
      of the patients was 41.32 +/- 19.21 years. Multivariate logistic regression
      indicated that mortality increased with age. Moreover, the odds of mortality was
      more in patients with Injury Severity Score (ISS) between 16 and 24 [OR: 12.94,
      95% CI (3.78-32.66), p=0.001] and injuries in the head and neck [OR: 7.92, 95% CI
      (4.18-14.99), p=0.020]. LOS in hospital was also higher in patients with ISS > 25
      [OR: 16.65, 95%CI (10.68-25.96), p=0.001]. Conclusion: Pedestrians have always
      been one of the most vulnerable road users. Our study indicated that the adverse
      consequences and mortalities in pedestrians increased with age. Hence, approaches
      are required to improve primary prevention programs and reduce deaths and
      injuries due to this major public health problem.

PMID- 29177175
TI  - Domestic Injuries among Children Under 7 Years of Age in Iran; The Baseline
      Results from the Iranian First Registry.
AB  - Objective: To investigate epidemiological aspects of injuries among Iranian
      children under 7 years of age using obtained data from a national registry.
      Methods: Injury data were derived from a national-based injury supervision system
      during 2000-2002. This registry involved all of home-related injuries for
      children less than 7 years of age that treated in health or emergency centers.
      The study population included 25% of Iranian people. The descriptive statistical
      methods were used for representing the distribution of the variables like age,
      sex, injury mechanisms, types of injuries, etc. Data were presented as mean +/-
      SD and proportions as appropriate. Results: Of the total 307,064 domestic
      injuries registered during 2000-2002, 77,500 cases (25.2%) were children. 70% of
      these children (54581 cases) were in age group of 1-5 years. The large fraction
      (58.8%) of injuries among children under 7 years of age went back to burn
      injuries. Cuts and lacerations were at the second level with 17.4%. 51% of
      injuries had contact with hot liquids. Of all children under 7 years of age
      injuries, 282 died, 86 were disabled, while the rest improved or being under
      treatment when recording data. Conclusion: Injuries, particularly burns
      (especially those who had contact with hot liquids that led into scald), are
      major public health problem that children under 7 years of age encounter.
      Therefore, it seems necessary to provide adequate plans to promote children under
      7 years of age safety issues.

PMID- 29177176
TI  - The Belief and Attitude of the Drivers Toward the Usage of Cellphone while
      Driving; A Population-Based Survey.
AB  - Objective: To presents a survey investigating differences between drivers'
      beliefs regarding utilizing cellphone when driving. Methods: In this population
      based survey, the participants who were studied in the North of Iran, Gorgan,
      were categorized as main urban and rural areas. A sample of 400 drivers, 92 women
      and 308 men, filled out the four sections questionnaire which was based on the
      Theory of Planned Behavior (TPB) used for measuring the differences between the
      drivers' opinions (attitudinal beliefs, normative beliefs, and perceived control
      behavioral beliefs) about utilizing a cell phone when driving along with their
      age and driving purpose. Data were collected by distributing the 68- query
      questionnaire between the drivers. Results: The MANOVA analysis showed that
      important discrepancies were found between the normative, control and behavioral
      beliefs of cellular phone users while driving. As expected, frequent business and
      younger users with sturdy intention expressed more benefits of further
      concentration on family members and fewer obstacles that would prevent them from
      utilizing cellphone when driving than older and frequently personal users.
      Conclusion: These results indicated that the benefits of utilizing cellphone
      while driving are greater than its dangers. To reduce cellphone utilization when
      driving and increase road safety, more effort is required to lower the perceived
      advantages of the behavior and to outstand the risks of this hazardous driving
      act.

PMID- 29177177
TI  - Does Intradisciplinary Conflict Influence to Outcomes of Emergency Medicine
      Residency Program? A Mixed Methods Study.
AB  - Objective: To explore impact of emergency medicine residency program on patient
      waiting times in emergency department (ED) and determine the associated factors.
      Methods: A two-phased sequential exploratory mixed-methods approach was used. The
      first phase was comprised of retrospective before-after design of ED encounters
      for a 3-month period, six months before and six months after the introduction of
      an emergency medicine residency program in an Iranian teaching hospital. The
      second phase included semi-structured interviews with five individuals which
      purposively selected to participate in qualitative design. Quantitative data were
      analysed descriptively and qualitative data were analysed using an iterative
      framework approach. Results: The most patients were admitted to the hospital in
      night shift, both before and after the resident EMS. No statistically significant
      differences were found among all of the waiting times during the two time periods
      except for the average time interval between admission and physician start time
      (p<0.0001), which increased (instead of reducing), and the average time interval
      between physician start time and first treatment measure (p<0.0001), which
      decreased during the year the residents began. The interviewees revealed the
      intradisciplinary conflicts and interferences existing between ED and other
      specialist departments, are main important factor to delayed processing of
      patients visits. Conclusion: This study has shown that intradisciplinary conflict
      would affect the outcomes of emergency medicine residency program and ED process.
      These new findings enhance the understanding of the nature of conflicts and will
      persuade policy makers that design a set of clinical practice guidelines to
      clarify the duties and responsibilities of parties involved in ED.

PMID- 29177178
TI  - Factors Affecting the Location of Road Emergency Bases in Iran Using Analytical
      Hierarchy Process (AHP).
AB  - Objective: To identify and prioritize factors affecting the location of road
      emergency bases in Iran using Analytical Hierarchy Process (AHP). Methods: This
      was a mixed method (quantitative-qualitative) study conducted in 2016. The
      participants in this study included the professionals and experts in the field of
      pre-hospital and road emergency services issues working in the Health Deputy of
      Iran Ministry of Health and Medical Education, which were selected using
      purposive sampling method. In this study at first, the factors affecting the
      location of road emergency bases in Iran were identified using literature review
      and conducting interviews with the experts. Then, the identified factors were
      scored and prioritized using the studied professionals and experts' viewpoints
      through using the analytic hierarchy process (AHP) technique and its related pair
      wise questionnaire. The collected data were analyzed using MAXQDA 10.0 software
      to analyze the answers given to the open question and Expert Choice 10.0 software
      to determine the weights and priorities of the identified factors. Results: The
      results showed that eight factors were effective in locating the road emergency
      bases in Iran from the viewpoints of the studied professionals and experts in the
      field of pre-hospital and road emergency services issues, including respectively
      distance from the next base, region population, topography and geographical
      situation of the region, the volume of road traffic, the existence of amenities
      such as water, electricity, gas, etc. and proximity to the village, accident
      prone sites, University ownership of the base site, and proximity to toll-house.
      Conclusion: Among the eight factors which were effective in locating the road
      emergency bases from the studied professionals and experts' perspectives,
      "distance from the next base" and "region population" were respectively the most
      important ones which had great differences with other factors.

PMID- 29177179
TI  - Endovascular Management of a Penetrating Zone III Retroperitoneal Gunshot Wound
      Injury; A Case Report.
AB  - Traumatic iliac vessels injuries secondary to gunshot wound can often be fatal at
      the scene. One of the intriguing complications of vascular injuries is
      arteriovenous fistula. If the patient survives, these lesions may often not be
      diagnosed on first evaluation and patients may present with clinical signs and
      symptoms years later. Open surgical repair can have prohibitive morbidity and
      mortality and endovascular techniques, an effective treatment alternative, can
      interrupt the abnormal vascular communication and preserve artery vein patency.
      We describe a unique case of iliac arteriovenous fistula (AVF), secondary to a
      bullet injury, identified by imaging studies and subsequently treated with
      endovascular surgery. In conclusion, traumatic AVF are rare. Traditional teaching
      mandates that zone III pelvic retroperitoneal hematomas secondary to penetrating
      trauma be explored.

PMID- 29177180
TI  - Isolated Traumatic Brachialis Muscle Tear: A Case Report and Review of
      Literature.
AB  - Isolated traumatic brachialis muscle tears are uncommonly reported - leading to
      occasional misdiagnosis and misdirected treatment. The rarity of brachialis
      muscle tear may promote misdiagnosis or mistreatment of this injury. We report an
      isolated brachialis muscle tear in a young female, possibly caused by strenuous
      exercise in the gymnasium. The diagnosis was made clinically and confirmed by
      magnetic resonance imaging. The patient was subsequently managed adequately with
      conservative treatment. We herein present a 35-year-old woman who was diagnosed
      with an acute brachialis muscle tear being diagnosed with a combination of
      clinical signs and imaging and successfully managed non-operatively. A
      chronologically arranged review of literature is also presented.

PMID- 29177181
TI  - Transient Diabetes Insipidus Following Thermal Burn; A Case Report and Literature
      Review.
AB  - Diabetes insipidus is a disease charaterised by increased urine production and
      thrist. Neurogenic diabetes insipidus following head trauma,autoimmune disease
      and infection is quite common but diabetes insipidus following thermal burn
      injury is a rare complication.We should know about this complication as its
      management need a comprehensive approach for satisfactory outcome. Thermal burn
      can cause different complications in early post burn period like electrolyte
      imbalance, dehydration, acute renal failure, but diabetes insipidus is a very
      rare and unusual complication that may come across in thermal burn. We should be
      aware about this condition to prevent and treat mortality and morbidity in burn
      patients. We have reported a case of transient diabetes insipidus in a patient of
      thermal burn in early post burn period. Patient was treated accordingly, leading
      to complete recovery.

PMID- 29177182
TI  - Glaucoma surgery and induced astigmatism: a systematic review.
AB  - Background: The refractive outcomes of glaucoma surgeries, particularly their
      effect on astigmatism, are incompletely understood. Main body: Trabeculectomy is
      associated with a considerable amount of with-the-rule astigmatic change in the
      immediate postoperative period. This is followed by a gradual against-the-rule
      shift. These changes are altered with the use of mitomycin C (MMC). Non
      penetrating surgery such as deep sclerectomy is also associated with a similar or
      smaller degree of induced astigmatism. Minimally invasive glaucoma surgery
      appears to be astigmatically neutral. There is no clear evidence regarding
      refractive outcomes of glaucoma drainage device surgery. Conclusions: Induced
      astigmatism may account for a reduction in unaided visual acuity in the early
      postoperative period following a successful trabeculectomy. These changes appear
      to stabilise at 3 months, and it would be prudent to defer the prescription of
      new glasses until this time. If sequential cataract surgery is to be performed,
      toric intraocular lenses can be a useful option for astigmatic correction.

PMID- 29177183
TI  - Molecular dynamics simulations in drug delivery research: Calcium chelation of
      G3.5 PAMAM dendrimers.
AB  - Poly(amido amine) (PAMAM) dendrimers have been considered as possible delivery
      systems for anticancer drugs. One potential advantage of these carriers would be
      their use in oral formulations, which will require absorption in the intestinal
      lumen. This may require the opening of tight junctions which may be enabled by
      reducing the Ca2+ concentration in the intestinal lumen, which has been shown as
      an absorption mechanism for EDTA (ethylenediaminetetraacetic acid). Using
      molecular dynamics simulations, we show that the G3.5 PAMAM dendrimers are able
      to chelate Ca2+ at similar proportions to EDTA, providing support to the
      hypothesis that oral formulations of PAMAM dendrimers could use this high
      chelating efficiency as a potential mechanism for permeating the tight junctions
      of the intestines if other formulation barriers could be overcome.

PMID- 29177184
TI  - Overrepresentation Analyses of Differentially Expressed Genes in the Smut Fungus
      Ustilago bromivora during Saprophytic and in planta Growth.
AB  - We have established the Ustilago bromivora-Brachypodium spp. interaction as a new
      model pathosystem for biotrophic fungal plant infections of the head smut type
      (Rabe et al., 2016). In this protocol, the methodology used for comparing gene
      expression between saprophytic and in planta growth of the fungus is described.
      The experimental and analytical pipeline, how next generation RNA sequencing
      (Illumina RNA-Seq) analysis can be used to obtain lists of genes significantly up
      or down regulated in planta in comparison to axenic culture is given.
      Furthermore, different methods to identify functional categories that are over-
      or under-represented among specific classes of genes are presented.

PMID- 29177185
TI  - A Murine Orthotopic Allograft to Model Prostate Cancer Growth and Metastasis.
AB  - Prostate cancer is one of the most common cancers in men in the United States.
      Comprehensive understanding of the biology contributing to prostate cancer will
      have important clinical implications. Animal models have greatly impacted our
      knowledge of disease and will continue to be a valuable resource for future
      studies. Herein, we describe a detailed protocol for the orthotopic engraftment
      of a murine prostate cancer cell line (Myc-CaP) into the anterior prostate of an
      immune competent mouse.

PMID- 29177186
TI  - Assessment of Murine Retinal Function by Electroretinography.
AB  - The electroretinogram (ERG) is a sensitive and noninvasive method for testing
      retinal function. In this protocol, we describe a method for performing ERGs in
      mice. Contact lenses on the mouse cornea measure the electrical response to a
      light stimulus of photoreceptors and downstream retinal cells, and the collected
      data are analyzed to evaluate retinal function.

PMID- 29177187
TI  - Increasing Research Productivity and Professional Development in Psychology With
      a Writing Retreat.
AB  - Writing is a core feature of the training requirements and career demands of
      psychology faculty members and graduate students. Within academic psychology,
      specifically, writing is vital for the generation of scientific knowledge through
      manuscripts and grant applications. Although resources exist regarding how to
      improve one's writing skills, few models have been described regarding how to
      promote a culture of writing productivity that realizes tangible deliverables,
      such as manuscripts and grant applications. In this article, we discuss the
      rationale, model, and initial outcome data of a writing retreat developed and
      implemented to increase research productivity among psychology faculty and
      trainees. We also review best practices for conducting writing retreats and
      identify key areas for future SoTL on advancing writing.

PMID- 29177189
TI  - A Neural Signature Encoding Decisions under Perceptual Ambiguity.
AB  - People often make perceptual decisions with ambiguous information, but it remains
      unclear whether the brain has a common neural substrate that encodes various
      forms of perceptual ambiguity. Here, we used three types of perceptually
      ambiguous stimuli as well as task instructions to examine the neural basis for
      both stimulus-driven and task-driven perceptual ambiguity. We identified a neural
      signature, the late positive potential (LPP), that encoded a general form of
      stimulus-driven perceptual ambiguity. In addition to stimulus-driven ambiguity,
      the LPP was also modulated by ambiguity in task instructions. To further specify
      the functional role of the LPP and elucidate the relationship between stimulus
      ambiguity, behavioral response, and the LPP, we employed regression models and
      found that the LPP was specifically associated with response latency and
      confidence rating, suggesting that the LPP encoded decisions under perceptual
      ambiguity. Finally, direct behavioral ratings of stimulus and task ambiguity
      confirmed our neurophysiological findings, which could not be attributed to
      differences in eye movements either. Together, our findings argue for a common
      neural signature that encodes decisions under perceptual ambiguity but is subject
      to the modulation of task ambiguity. Our results represent an essential first
      step toward a complete neural understanding of human perceptual decision making.

PMID- 29177188
TI  - alpha-Synuclein-Dependent Calcium Entry Underlies Differential Sensitivity of
      Cultured SN and VTA Dopaminergic Neurons to a Parkinsonian Neurotoxin.
AB  - Parkinson's disease (PD) is a debilitating neurodegenerative disease
      characterized by a loss of dopaminergic neurons in the substantia nigra (SN).
      Although mitochondrial dysfunction and dysregulated alpha-synuclein (aSyn)
      expression are postulated to play a role in PD pathogenesis, it is still debated
      why neurons of the SN are targeted while neighboring dopaminergic neurons of the
      ventral tegmental area (VTA) are spared. Using electrochemical and imaging
      approaches, we investigated metabolic changes in cultured primary mouse midbrain
      dopaminergic neurons exposed to a parkinsonian neurotoxin, 1-methyl-4
      phenylpyridinium (MPP+). We demonstrate that the higher level of neurotoxicity in
      SN than VTA neurons was due to SN neuron-specific toxin-induced increase in
      cytosolic dopamine (DA) and Ca2+, followed by an elevation of mitochondrial Ca2+,
      activation of nitric oxide synthase (NOS), and mitochondrial oxidation. The
      increase in cytosolic Ca2+ was not caused by MPP+-induced oxidative stress, but
      rather depended on the activity of both L-type calcium channels and aSyn
      expression, suggesting that these two established pathogenic factors in PD act in
      concert.

PMID- 29177191
TI  - Motherhood and the Wages of Women in Professional Occupations.
AB  - It is well established that mothers are paid less than childless women and that
      fathers tend to earn higher wages relative to childless men, but we do not know
      whether these findings apply to workers in all occupations. Using IPUMS and ACS
      data from 1980 and 2010, we examine the family wage gap for highly educated
      professionals, the most advantaged sector of the occupational distribution.
      Results indicate that the size of the negative wage differential for motherhood
      has declined over time in all professions. Moreover, in the traditionally male
      dominated professions of STEM, medicine, and law, women with children experience
      a positive wage differential, whereas their counterparts in female-dominated
      professions continue to experience a negative one. The positive differential for
      fatherhood has remained stable over time. These findings underscore the growing
      heterogeneity of women's experiences in combining work and family and raise
      important questions for further research.

PMID- 29177190
TI  - Functional germline variants as potential co-oncogenes.
AB  - Germline variants that affect the expression or function of proteins contribute
      to phenotypic variation in humans and likely determine individual characteristics
      and susceptibility to diseases including cancer. A number of high penetrance
      germline variants that increase cancer risk have been identified and studied, but
      germline functional polymorphisms are not typically considered in the context of
      cancer biology, where the focus is primarily on somatic mutations. Yet, there is
      evidence from familial cancers indicating that specific cancer subtypes tend to
      arise in carriers of high-risk germline variants (e.g., triple negative breast
      cancers in mutated BRCA carriers), which suggests that pre-existing germline
      variants may determine which complementary somatic driver mutations are needed to
      drive tumorigenesis. Recent genome sequencing studies of large breast cancer
      cohorts reported only a handful of highly recurrent driver mutations, suggesting
      that different oncogenic events drive individual cancers. Here, we propose that
      germline polymorphisms can function as oncogenic modifiers, or co-oncogenes, and
      these determine what complementary subsequent somatic events are required for
      full malignant transformation. Therefore, we propose that germline aberrations
      should be considered together with somatic mutations to determine what genes
      drive cancer and how they may be targeted.

PMID- 29177192
TI  - Protein chainmail variants in dsDNA viruses.
AB  - First discovered in bacteriophage HK97, biological chainmail is a highly stable
      system formed by concatenated protein rings. Each subunit of the ring contains
      the HK97-like fold, which is characterized by its submarine-like shape with a 5
      stranded beta sheet in the axial (A) domain, spine helix in the peripheral (P)
      domain, and an extended (E) loop. HK97 capsid consists of covalently-linked
      copies of just one HK97-like fold protein and represents the most effective
      strategy to form highly stable chainmail needed for dsDNA genome encapsidation.
      Recently, near-atomic resolution structures enabled by cryo electron microscopy
      (cryoEM) have revealed a range of other, more complex variants of this strategy
      for constructing dsDNA viruses. The first strategy, exemplified by P22-like
      phages, is the attachment of an insertional (I) domain to the core 5-stranded
      beta sheet of the HK97-like fold. The atomic models of the Bordetella phage BPP-1
      showcases an alternative topology of the classic HK97 topology of the HK97-like
      fold, as well as the second strategy for constructing stable capsids, where an
      auxiliary jellyroll protein dimer serves to cement the non-covalent chainmail
      formed by capsid protein subunits. The third strategy, found in lambda-like
      phages, uses auxiliary protein trimers to stabilize the underlying non-covalent
      chainmail near the 3-fold axis. Herpesviruses represent highly complex viruses
      that use a combination of these strategies, resulting in four-level hierarchical
      organization including a non-covalent chainmail formed by the HK97-like fold
      domain found in the floor region. A thorough understanding of these structures
      should help unlock the enigma of the emergence and evolution of dsDNA viruses and
      inform bioengineering efforts based on these viruses.

PMID- 29177193
TI  - Percutaneous Management of a Pyocystic Fistulizing Continent Urinary Diversion.
AB  - Background: Continent diversions have since been performed with increasing
      frequency since the 1950s, with some providers espousing the use of orthotopic
      diversions as being the new gold standard. However, patients must be counseled to
      take great care in the maintenance of their diversions because of complications
      such as metabolic abnormalities, pouch stones, and mucus retention. Case Report:
      A 21-year-old male with a history of posterior urethral valves underwent a
      continent catheterizable diversion as a child. He is undocumented and without
      health insurance and as a result unable to follow-up with an urologist for >10
      years. He subsequently develops pyocystis with cutaneous fistulization and pouch
      stones necessitating percutaneous management. Conclusion: Patients may benefit
      greatly from a continent urinary diversion, however, selection must include
      patients who are able to maintain their pouch and follow-up with their providers
      to avoid major complications that may occur up to years following the procedure.

PMID- 29177194
TI  - Primary Upper Urinary Tract Small Cell Carcinoma: A Case Series and Literature
      Review.
AB  - Background: Primary upper urinary tract small cell carcinoma (SCC) is exceedingly
      rare with < 30 cases reported in the literature. Little is known about the
      incidence, diagnosis, treatment, and outcomes in these patients. We present a
      series of three patients with primary upper tract SCC. Case Presentation: Patient
      1 is an 89-year-old Caucasian male who presented with hydroureteronephrosis and a
      mass in the proximal right ureter. Biopsy revealed SCC. Without further
      intervention, the patient died 2 months after his diagnosis. Patient 2 is a 67
      year-old Caucasian female who underwent left laparoscopic nephroureterectomy for
      primary distal ureteral SCC, pT4N1M0. She developed lymphadenopathy and completed
      external beam radiation to the pelvis and four courses of cisplatin-based
      chemotherapy. She died from metastatic disease 7 months after diagnosis. Patient
      3 is a 45-year-old female who underwent open right radical nephrectomy,
      retroperitoneal lymph node dissection, and hepatic metastasectomy for metastatic
      primary upper tract SCC, pT3N1M1. She underwent two subsequent retroperitoneal
      debulking procedures for recurrence followed by treatment with octreotide. She
      developed widespread metastasis and was treated with temozolomide and
      capecitabine before her death 80 months after diagnosis. Conclusion: This series
      contributes to the limited knowledge of the management and natural course of
      primary upper tract SCC. Patient 1 represents the first disease-specific
      mortality reported in a patient who received no therapy. Patient 3 represents the
      longest reported survival with metastatic disease, and the first treated with
      octreotide. The patient was managed with aggressive repeat surgical resection and
      exhibited 2 years of progression-free survival on octreotide. Emphasis should be
      placed on aggressive resection of all visible disease combined with the use of
      multimodal adjuvant chemoradiation for selected patients in this rare disease.

PMID- 29177195
TI  - Total Preperitoneal Robot-Assisted Kidney Transplantation.
AB  - To date, kidney transplant recipients have always undergone open surgery. The
      type and length of the wound vary, but most commonly, a modified Gibson's
      incision is made in the lower abdomen for the transplantation. Risk factors for
      wound complications are well defined in general surgery literature. The
      laparoscopic kidney transplantation (LKT) technique has been developed recently,
      and several teams have published studies on the intraperitoneal technique. In
      this case report, we present our technique of total preperitoneal LKT using the
      Da Vinci robotic surgical system.

PMID- 29177196
TI  - To Refer or Not to Refer: General Pediatricians' Perspectives on Their Role in
      Caring for Transgender Youth.
AB  - Little is known about general pediatricians' experience and knowledge regarding
      the care of transgender youth. We surveyed N=50 general pediatricians practicing
      in an integrated Midwest health system. Few respondents had participated in
      medical management care for transgender patients, but one-third were willing to
      do so if training opportunities were made available. Notably, <60% of respondents
      were comfortable providing routine care for transgender youth. At a minimum,
      pediatricians need the training to feel capable of providing routine care for
      transgender pediatric patients. In addition, opportunities for training should be
      offered to those who are willing to learn about medical management of transgender
      youth.

PMID- 29177197
TI  - Foam Sclerotherapy during Shunt Surgery for Portal Hypertension and Varices.
AB  - Objective: This preliminary study investigated the clinical safety and efficacy
      of foam sclerotherapy during shunt surgery to treat portal hypertension and
      gastroesophageal varices. Methods: Seven patients with confirmed portal
      hypertension and a variceal bleeding history underwent mesocaval shunt with
      simultaneous polidocanol foam injection into the varices. Computed tomography and
      endoscopic reviews were conducted within two weeks following the procedures and
      around six months later. Results: Six patients underwent side-to-side mesocaval
      shunt. One received a prosthetic mesocaval shunt. Polidocanol foam was injected
      into the gastric varices or the inferior mesenteric vein during the surgery.
      Surgical success and survival was achieved in all patients. Gastric ulcer
      formation and thrombocytopenia occurred in one patient respectively, which were
      ameliorated by conservative treatment. During 12 to 24 months' follow-up, three
      patients had obvious decrease or eradication of gastroesophageal varices; four
      patients had obvious decrease of gastric varices but residual esophageal varices;
      and all patents had unobstructed shunts. Encephalopathy occurred in one patient
      two months postoperatively. No sclerosant-related complications were observed and
      no postoperative recurrent variceal bleeding occurred. Conclusions: Foam
      sclerotherapy during shunt surgery is safe and effective for portal hypertension
      and varices treatment.

PMID- 29177198
TI  - Attention modulates perception of visual space.
AB  - Attention readily facilitates the detection and discrimination of objects, but it
      is not known whether it helps to form the vast volume of visual space that
      contains the objects and where actions are implemented. Conventional wisdom
      suggests not, given the effortless ease with which we perceive three-dimensional
      (3D) scenes on opening our eyes. Here, we show evidence to the contrary. In
      Experiment 1, the observer judged the location of a briefly presented target,
      placed either on the textured ground or ceiling surface. Judged location was more
      accurate for a target on the ground, provided that the ground was visible and
      that the observer directed attention to the lower visual field, not the upper
      field. This reveals that attention facilitates space perception with reference to
      the ground. Experiment 2 showed that judged location of a target in mid-air, with
      both ground and ceiling surfaces present, was more accurate when the observer
      directed their attention to the lower visual field; this indicates that the
      attention effect extends to visual space above the ground. These findings
      underscore the role of attention in anchoring visual orientation in space, which
      is arguably a primal event that enhances one's ability to interact with objects
      and surface layouts within the visual space. The fact that the effect of
      attention was contingent on the ground being visible suggests that our
      terrestrial visual system is best served by its ecological niche.

PMID- 29177199
TI  - Predicting tacrolimus concentrations in children receiving a heart transplant
      using a population pharmacokinetic model.
AB  - Objective: Immunosuppressant therapy plays a pivotal role in transplant success
      and longevity. Tacrolimus, a primary immunosuppressive agent, is well known to
      exhibit significant pharmacological interpatient and intrapatient variability.
      This variability necessitates the collection of serial trough concentrations to
      ensure that the drug remains within therapeutic range. The objective of this
      study was to build a population pharmacokinetic (PK) model and use it to
      determine the minimum number of trough samples needed to guide the prediction of
      an individual's future concentrations. Design setting and patients: Retrospective
      data from 48 children who received tacrolimus as inpatients at Primary Children's
      Hospital in Salt Lake City, Utah were included in the study. Data were collected
      within the first 6 weeks after heart transplant. Outcome measures: Data analysis
      used population PK modelling techniques in NONMEM. Predictive ability of the
      model was determined using median prediction error (MPE, a measure of bias) and
      median absolute prediction error (MAPE, a measure of accuracy). Of the 48
      children in the study, 30 were used in the model building dataset, and 18 in the
      model validation dataset. Results: Concentrations ranged between 1.5 and 37.7
      MUg/L across all collected data, with only 40% of those concentrations falling
      within the targeted concentration range (12 to 16 MUg/L). The final population PK
      model contained the impact of age (on volume), creatinine clearance (on
      elimination rate) and fluconazole use (on elimination rate) as covariates. Our
      analysis demonstrated that as few as three concentrations could be used to
      predict future concentrations, with negligible bias (MPE (95% CI)=0.10% (-2.9% to
      3.7%)) and good accuracy (MAPE (95% CI)=24.1% (19.7% to 27.7%)). Conclusions: The
      use of PK in dose guidance has the potential to provide significant benefits to
      clinical care, including dose optimisation during the early stages of therapy,
      and the potential to limit the need for frequent drug monitoring.

PMID- 29177200
TI  - Spatial distribution of uranium in mice kidneys detected by laser ablation
      inductively coupled plasma mass spectrometry.
AB  - The aim of the study is to better understand where uranium deposits in mice
      kidneys. The spatial distribution of uranium was examined in the kidneys of
      C57BL/6 mice using laser ablation inductively coupled plasma mass spectrometry
      (LA-ICP-MS). Mice were exposed to varying levels of uranyl nitrate in their
      drinking water. Calibration standards were developed to allow for semi
      quantitative measurement of uranium in the cortical and medullary regions of mice
      kidney by LA-ICP-MS. Scanning electron microscopy was used to image the ablation
      patterns on the kidney. Uranium levels were observed to increase in kidney tissue
      as uranyl nitrate treatment exposure levels increased. A trend towards a higher
      uranium concentration in the medullary versus cortical region of the kidneys was
      observed. These results show the usefulness of LA-ICP-MS in toxicity studies by
      providing a quantitative, spatial assessment of uranium deposition in a target
      organ.

PMID- 29177201
TI  - In Situ Visualization for 3D Agent-Based Vocal Fold Inflammation and Repair
      Simulation.
AB  - A fast and insightful visualization is essential in modeling biological system
      behaviors and understanding underlying inter-cellular mechanisms. High fidelity
      models produce billions of data points per time step, making in situ
      visualization techniques extremely desirable as they mitigate I/O bottlenecks and
      provide computational steering capability. In this work, we present a novel high
      performance scheme to couple in situ visualization with the simulation of the
      vocal fold inflammation and repair using little to no extra cost in execution
      time or computing resources. The visualization component is first optimized with
      an adaptive sampling scheme to accelerate the rendering process while maintaining
      the precision of the displayed visual results. Our software employs VirtualGL to
      perform visualization in situ. The scheme overlaps visualization and simulation,
      resulting in the optimal utilization of computing resources. This results in an
      in situ system biology simulation suite capable of remote simulation of 17
      million biological cells and 1.2 billion chemical data points, remote
      visualization of the results, and delivery of visualized frames with aggregated
      statistics to remote clients in real-time.

PMID- 29177202
TI  - Applying physical science techniques and CERN technology to an unsolved problem
      in radiation treatment for cancer: the multidisciplinary 'VoxTox' research
      programme.
AB  - The VoxTox research programme has applied expertise from the physical sciences to
      the problem of radiotherapy toxicity, bringing together expertise from
      engineering, mathematics, high energy physics (including the Large Hadron
      Collider), medical physics and radiation oncology. In our initial cohort of 109
      men treated with curative radiotherapy for prostate cancer, daily image guidance
      computed tomography (CT) scans have been used to calculate delivered dose to the
      rectum, as distinct from planned dose, using an automated approach. Clinical
      toxicity data have been collected, allowing us to address the hypothesis that
      delivered dose provides a better predictor of toxicity than planned dose.

PMID- 29177203
TI  - Modeling cancer rearrangement landscapes.
AB  - Cancer genome sequences contain footprints of somatic mutational processes, whose
      analysis in large tumor sequencing datasets has revealed novel mutational
      signatures, correlative features of variant topography, and complex events. Many
      of these analytic results have yet to reconciled with decades of mechanistic
      genome integrity research performed in controlled model systems. However, a new
      generation of genome-integrity experiments combining computational modeling, data
      analytics, and high-throughput sequencing are emerging to link mechanisms to
      patterns. Conversely, analytic studies evaluating quantitative footprints of
      specific genome integrity hypotheses will be critical in fitting naturally
      occurring mutational patterns to the predictions of a particular mechanistic
      model. Such quantitative and mechanistic studies will form the foundation of an
      emerging systems biology of genome integrity.

PMID- 29177205
TI  - New evidence for chemical fractionation of radioactive xenon precursors in
      fission chains.
AB  - Mass-spectrometric analyses of Xe released from acid-treated U ore reveal that
      apparent Xe fission yields significantly deviate from the normal values. The
      anomalous Xe structure is attributed to chemically fractionated fission (CFF),
      previously observed only in materials experienced neutron bursts. The least
      retentive CFF-Xe isotopes, 136Xe and 134Xe, typically escape in 2:1 proportion.
      Xe retained in the sample is complimentarily depleted in these isotopes. This
      nucleochemical process allows understanding of unexplained Xe isotopic structures
      in several geophysical environments, which include well gasses, ancient
      anorthosite, some mantle rocks, as well as terrestrial atmosphere. CFF is likely
      responsible for the isotopic difference in Xe in the Earth's and Martian
      atmospheres and it is capable of explaining the relationship between two major
      solar system Xe carriers: the Sun and phase-Q, found in meteorites.

PMID- 29177204
TI  - Nutritional Renaissance and Public Health Policy.
AB  - The science of nutrition has long been entrapped in reductionist interpretation
      of details, a source of great confusion. However, if nutrition is defined as the
      integration of countless nutrient factors, metabolic reactions and outcomes,
      biologically orchestrated as in symphony, its relevance for personal and public
      health would be less confusing and more productive. This more wholistic
      interpretation may be observed at the cellular and physiological levels and may
      be described, in part, by the concept of pleiotropy (multiple cell-based effects
      from one nutrient source), together with its more expansive cousin, epitropy
      (multiple cell-based effects from multiple nutrients). There are many
      consequences. First, wholistic interpretation helps to explain the profound but
      little-known health benefits of whole plant-based foods (not vegan or vegetarian)
      when compared with whole animal-based foods and/or with the nutritionally
      variable convenience foods (generally high in fat, salt, refined carbohydrates
      and low in complex carbohydrates). Second, wholistic interpretation explains why
      the U.S. Dietary Guidelines and related public policies, which are primarily
      conceived from reductionist reasoning, serve political agendas so effectively. If
      diet and health advisories were to acknowledge the biological complexity of
      nutrition, then make greater use of deductive (top down) instead of inductive
      (bottom up) reasoning, there would be less confusion. Third, wholistic nutrition,
      if acknowledged, could greatly help to resolve the highly-polarized, virtually
      intractable political debate on health care. And fourth, this definition tells
      why nutrition is rarely if ever offered in medical school training, is not one of
      the 130 or so medical specialties, and does not have a dedicated research
      institute at U.S. National Institutes of Health. Nutrition is a wholistic science
      whereas medical practice is reductionist, a serious mismatch that causes biased
      judgement of nutrition. But this dichotomy would not exist if the medical
      practice profession were to understand and adopt wholistic interpretation.
      Reductionist research, however, is crucially important because its findings
      provide the granular structure for wholistic interpretation-these two
      philosophies are inescapably interdependent. Evidence obtained in this manner
      lends strong support to the suggestion that nutrition is more efficacious and far
      more affordable in maintaining and restoring (treating) health than all the pills
      and procedures combined. Admittedly, this is a challenging paradigm for the
      domain of medical science itself.

PMID- 29177206
TI  - The Importance of Mammalogy, Infectious Disease Research, and Biosafety in the
      Field.
AB  - Large amounts of data and multitudes of publications have been independently
      generated by researchers in mammalogy and infectious diseases. The frequent
      confluence of these fields in epidemiological research as well as the facility of
      the data generated to be used in applied methods (e.g., conservation, public
      outreach, public health interventions) suggests that the intersection of these
      fields is important not only to their committed scientists but also to other
      areas of investigation, including public health. Given the increased frequency
      with which researchers in these fields interact with potentially infected humans,
      animals, and tissues, their occupations present a higher risk of exposure to a
      variety of pathogens than those in other fields of biology or among most jobs of
      the general public. However, a variety of methods are available for minimizing
      this risk, including increasing awareness of potential risks, using medical
      prophylaxes (when available), properly employing personal protective equipment,
      and using adequate disinfectants. Although instances of serious illness from
      zoonotic diseases among field researchers may be uncommon, they do occur; the
      purpose of this document is to increase awareness of risks that researchers
      principal investigators and students alike-face and highlight steps and resources
      that can mitigate those risks.

PMID- 29177207
TI  - Can pancreatic cancer behavior be predicted based on computed tomography
      measurements of fat and muscle mass?
AB  - : Many studies purport that obesity, and specifically visceral fat, impact
      survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. However,
      these studies involve crude measures of obesity [eg, body mass index (BMI)] or
      visceral fat [eg, linear measurements on computed tomographic (CT) scans]. Some
      studies purport that weight loss and muscle wasting (ie, sarcopenia) presage poor
      survival in these patients. This study was undertaken to accurately measure and
      reexamine the impact of visceral fat, subcutaneous fat, and sarcopenia on
      pancreatic cancer. Materials and methods: CT scans of 100 patients undergoing
      pancreaticoduodenectomy for pancreatic adenocarcinoma were reviewed using
      specialized software to precisely determine the cross-sectional area (CSA) of
      subcutaneous fat, visceral fat, and psoas muscles at the level of L5 vertebra. In
      addition, linear measurements of subcutaneous fat and visceral fat were
      undertaken. Measures of cancer progression included tumor (T) status, nodal (N)
      status, American Joint Committee on Cancer stage, and overall survival after
      resection. Regression analysis was utilized, with and without standardization of
      all measurements to body size. Median data are presented. Results: The median
      patient age was 67 years, with a BMI of 24 kg/m2. Cancer stage was IIB for 60% of
      patients. BMI, CSA of visceral fat, CSA for subcutaneous fat, CSA for psoas
      muscles, and linear measurements of visceral and subcutaneous fat were not
      significantly related to any measures of cancer progression or survival.
      Standardization to body size did not demonstrate any relationships with cancer
      progression or survival. Conclusions: Precise and reproducible measures of
      visceral fat, subcutaneous fat, and muscle mass, even when standardized to body
      size, do not predict cancer progression or survival in patients undergoing
      pancreaticoduodenectomy for pancreatic adenocarcinoma. Pancreatic cancer biology
      and behavior is too complex to predict with a CT scanner. The main focus of
      pancreatic cancer research should continue to be at the molecular, genetic, and
      immunologic levels.

PMID- 29177208
TI  - Management of peritoneal surface malignancies in laparoscopic era: a concise
      review.
AB  - Peritoneal carcinomatosis is seldom curable. Maximal cytoreductive surgery
      combined with hyperthermic intraperitoneal chemotherapy has been used in efforts
      to improve survival. There has been a recent explosion of interest in this
      modality of treatment with various centers employing its use throughout the
      world. This is a complex procedure associated with significant morbidity and
      mortality. This makes patient selection very critical and hence there has been
      immense interest in the evaluation of various prognostic indicators being
      evaluated. In addition, with the advent of minimally invasive surgery,
      laparoscopy is being increasingly utilized in different capacity. Newer
      indications for treatment and possible prevention of peritoneal carcinomatosis
      are being evaluated especially in colorectal cancer. The aim of this brief review
      is to synthesize and present the recent data available regarding the outcomes and
      evolving trends associated with cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy.

PMID- 29177209
TI  - H. pylori infection and gastric cancer in Bangladesh: a case-control study.
AB  - Background: Like that of other Asian countries gastric cancer (GC) is also a
      leading cancer in Bangladesh and also a cause for cancer-related mortality.
      Infection with Helicobacter pylori (H. pylori) is the strongest recognized risk
      factor for gastric adenocarcinoma. The infection is also prevalent in common
      people. This case-control study was carried out to find an association between GC
      and H. pylori infection in the community. Materials and Methods: To evaluate
      association of H. pylori and carcinoma of stomach this study was conducted at
      National Institute of Cancer Research & Hospital, Dhaka from January 2013 to
      December 2014. H. pylori status was determined serologically by using H. pylori
      kit in the department of Biochemistry laboratory of Bangabandhu Sheikh Mujib
      Medical University. In total, 114 patients with GC and 520 patients not having GC
      were studied as controls. Logistic regression method was used to calculate the
      odds ratio. Results: Significantly more patients in the case group (86.8%) were
      found to be seropositive for H. pylori antigen in contrast to the control group
      (67.5%). All of the cases in the present study were in advanced stage. No
      significant association between H. pylori seropositivity and tumor location was
      found. It was noted that undifferentiated gastric carcinoma had slightly more
      association with H. pylori infection. Younger H. pylori-infected patients had
      been found to be at higher relative risk for GC than older patients. Conclusion:
      As there is a strong association found between GC and H. pylori infection special
      emphasis to eradicate H. pylori infection might reduce the incidence of this
      dreadly disease.

PMID- 29177210
TI  - Patients unfit for neoadjuvant therapy may still undergo resection of locally
      advanced esophageal or esophagogastric junctional cancer with acceptable
      oncological results.
AB  - : Neoadjuvant chemotherapy (NA) is routinely offered to patients undergoing
      resection for locally advanced (>=cT3Nx or cTxN+) esophageal or esophagogastric
      junctional (EGJ) cancer in the United Kingdom. Patients with comorbidity
      precluding the use of NA can be considered for resection yet the effect of
      omitting NA on survival is unclear. Methods: Retrospective review of
      prospectively collected clinical data from patients undergoing attempted curative
      therapy for >=cT3Nx or cTxN+ esophageal or EGJ (Siewert type I-III) cancer
      between 2001 and 2013. Results: NA was commenced in 289 patients and primarily
      comprised 2 cycles of cisplatin and 5-fluorouracil (264 patients, 91%). Surgery
      alone was planned for 82 patients with NA omitted due to comorbidity. Patients
      undergoing surgery alone were matched for clinical variables and stage with those
      undergoing NA but were significantly older (mean=8 y, P<0.001). NA was associated
      with an improved median overall survival of 28.7 months, compared with 20.9
      months for patients undergoing surgery alone (P=0.008). Patients undergoing
      surgery alone had a 90-day postoperative mortality rate of 10% compared with 3%
      for those undergoing NA (P=0.011). In patients discharged postoperatively, the
      median overall survival benefit of NA was 2.7 months (P=0.048). Those 19% of
      patients experiencing a significant histologic response to NA demonstrated
      further improved survival. Conclusions: NA improves survival in patients
      undergoing resection for locally advanced esophageal or EGJ cancer; however, the
      median benefit is <3 months in patients discharged postoperatively. Patients
      precluded from NA achieve acceptable oncological results but experience a higher
      risk of perioperative mortality.

PMID- 29177211
TI  - Functional rehabilitation in advanced intraoral cancer.
AB  - : Modern treatment of advanced intraoral cancer involves multidisciplinary teams
      with use of complicated reconstructive techniques to provide improved survival
      with optimal rehabilitation. Mastication is an important part of this process,
      and it can be severely impaired by tumor ablation. Whether flap reconstruction is
      a determinant factor in dental rehabilitation is still in debate. Patients and
      methods: Thirty-five patients with advanced intraoral cancer were reviewed to
      determine dental rehabilitation of different reconstructive techniques. The
      patients were treated with a multidisciplinary team approach. The patients'
      demographics, primary treatment, reconstructive surgery, dental rehabilitation,
      and functional outcome were recorded and analyzed. Results: Nine patients had
      Stadium III disease, and 26 patients had stadium IV. Thirty-two patients (91.42%)
      received postoperative radiotherapy. Masticatory and dental functional
      rehabilitation of patients was very poor. Only 15 patients (42.86%) could eat a
      normal diet, whereas 18 patients (51.42%) could manage only soft diets, and 2
      patients (5.72%) could only be fed with a liquid diet. Denture rehabilitation was
      even more frustrating and had a direct impact on masticatory rehabilitation. Only
      10 patients (28.57%) could use dentures postoperatively and 40% of patients (14
      patients) could not use any denture at all. Above all reconstructive techniques,
      the free radial forearm flap provides the best functional outcome. Conclusions:
      Reconstruction of advanced intraoral cancer results in poor denture
      rehabilitation, especially when bulky flaps are used. If massive resections are
      necessary, the free radial forearm flap reconstruction provides the best
      functional outcome.

PMID- 29177212
TI  - Spontaneous splenic artery rupture in a patient with an unclassified malignant
      spindle cell tumor of the spleen: report of a case.
AB  - The purpose of this paper was to describe an unusual manifestation of a sarcoma
      of the spleen and to raise awareness for spontaneous rupture of the splenic
      vessels in patients with splenic tumors. A 70-year-old man was admitted to our
      institution, suffering from left upper quadrant abdominal pain. Upon physical
      examination, a large and tender abdominal mass was palpated. Abdominal computed
      tomography showed a heterogenous enlarged spleen with active contrast
      extravasation from the splenic artery, free intraperitoneal fluid, and a
      retroperitoneal hematoma. The patient was treated with angioembolization of the
      splenic artery. Because of rebleeding, splenectomy was performed. Pathology
      revealed the spleen to be involved with an unclassified malignant spindle cell
      neoplasm. We concluded that in the case of spontaneous rupture of the splenic
      artery, accompanied with a radiologic appearance of an enlarged spleen, the
      diagnosis of sarcoma should be included in the differential diagnosis.

PMID- 29177214
TI  - How to get shortlisted for medical jobs.
AB  - Progressing up the medical career ladder is a tough business. Most medical and
      surgical applications center the requirement for a holistic, balanced individual.
      As a result, there are usually specific marking criteria in predefined sections.
      This article provides a guide into what employers are looking for and how best to
      build your portfolio in these areas.

PMID- 29177213
TI  - Sulfonylureas (not metformin) improve survival of patients with diabetes and
      resectable pancreatic adenocarcinoma.
AB  - : Patients with pancreatic adenocarcinoma have an increased propensity for
      diabetes. Recent studies suggest patients with diabetes and pancreatic
      adenocarcinoma treated with metformin have increased survival. This study was
      undertaken to determine whether metformin use is associated with increased
      survival in patients with pancreatic adenocarcinoma. Methods: Patients who
      underwent pancreaticoduodenectomy for pancreatic adenocarcinoma from 1991 to 2013
      were included in this study. Survival was evaluated by Kaplan-Meier analysis.
      Median data are reported. Significance was accepted with 95% probability.
      Results: Of 414 patients undergoing pancreaticoduodenectomy for pancreatic
      adenocarcinoma, 132 (32%) were diabetic. Of patients with diabetes, 35 (27%) were
      diet-controlled, 34 (26%) were treated with insulin alone, 18 (14%) were treated
      with metformin alone, 14 (10%) were treated with sulfonylureas alone, 7 (5%) were
      taking sulfonylureas with insulin, and 24 (18%) patients were taking metformin
      with sulfonylureas and/or insulin. Patients with/without diabetes not taking
      sulfonylureas had survival of 16.4 months compared with patients taking
      sulfonylureas who achieved survival of 27.5 months after undergoing
      pancreaticoduodenectomy (P<0.05). Conclusions: Patients taking sulfonylureas with
      or without other therapy had improved survival compared with patients not taking
      sulfonylureas after pancreaticoduodenectomy. Metformin does not seem to be
      beneficial for patients with resectable disease, but may be beneficial for
      patients with unresectable and/or metastatic disease as shown in prior studies.
      The use of sulfonylureas is associated with a survival benefit for patients
      undergoing resection for pancreatic adenocarcinoma. Tumor staging and margin
      status continue to be the overriding predictors of survival in patients with
      resectable pancreatic adenocarcinoma, not metformin therapy.

PMID- 29177215
TI  - Reflective practice in health care and how to reflect effectively.
AB  - Reflective practice is a paper requirement of your career progression in health
      care. However, if done properly, it can greatly improve your skills as a health
      care provider. This article provides some structure to reflective practice to
      allow a health care provider to engage more with reflective practice and get more
      out of the experience.

PMID- 29177216
TI  - How to succeed at medical interviews.
AB  - Few people truly relish being interviewed. But as a professional, you will go
      through a number of interviews in your life that will affect your career
      progression. In this article, we provide some tips on how best to prepare for a
      medical interview, both in terms of your portfolio and interview practice. Advice
      is also given on how to maximize performance during the interview and gain the
      most from reflection afterwards.

PMID- 29177217
TI  - How to design and deliver a local teaching program.
AB  - Teaching is an invaluable aspect of any medical or surgical career. Many trainees
      will find themselves delivering teaching at several stages in their career and in
      this "How to" article we explain how to design, set up, and deliver a successful
      teaching program, as well as how to evidence this in your portfolio.

PMID- 29177218
TI  - How to conduct a clinical audit and quality improvement project.
AB  - Audits and quality improvement projects are vital aspects of clinical governance
      and continual service improvement in medicine. In this article we describe the
      process of clinical audit and quality improvement project. Guidance is also
      provided on how to design an effective audit and bypass barriers encountered
      during the process.

PMID- 29177219
TI  - How to deliver an oral presentation.
AB  - Delivering an oral presentation in conferences and meetings can seem daunting.
      However, if delivered effectively, it can be an invaluable opportunity to
      showcase your work in front of peers as well as receive feedback on your project.
      In this "How to" article, we demonstrate how one can plan and successfully
      deliver an engaging oral presentation.

PMID- 29177220
TI  - How to publish a book.
AB  - Writing a book can seem like a daunting prospect. However, with the right idea,
      motivation, and effort, it is entirely possible. In this "How to" article we
      demonstrate and explain how one can take their book idea and successfully deliver
      it to publication.

PMID- 29177221
TI  - Why apply for an intercalated research degree?
AB  - Intercalated degrees are commonly undertaken as part of the medical undergraduate
      course. In this article, we discuss the advantages and disadvantages of
      intercalation, along with alternatives that could be considered.

PMID- 29177222
TI  - How to organize a medical elective.
AB  - The medical elective is often considered a major highlight of the medical school
      experience. However, organizing an elective can be a daunting experience. From
      selecting a destination, to securing bursaries, the road is fraught with
      uncertainty. In this article, we provide some guidance on how to successfully
      organize a medical elective. This includes the selection of the destination;
      options for research or clinical practice and tips for budgeting and acquiring
      travel bursaries.

PMID- 29177223
TI  - How to study effectively.
AB  - The ability to study effectively is an essential part of completing a medical
      degree. To cope with the vast amount of information and skills needed to be
      acquired, it is necessary develop effective study techniques. In this article we
      outline the various methods students can use to excel in upcoming examinations.

PMID- 29177224
TI  - How to write a medical CV.
AB  - A medical curriculum vitae remains an important document that has 2 main roles:
      to distinguish candidates applying for various positions, whether that be jobs,
      posts, grants and it provides a means of keeping an up-to-date record of all your
      achievements and skills gained thus far. This article provides detailed guidance
      on how to structure an effective curriculum vitae to maximize your chances of
      success when applying for these positions.

PMID- 29177225
TI  - The principles of the surgical management of gastric cancer.
AB  - Surgery is the only curative therapy for gastric cancer but most operable gastric
      cancer presents in a locally advanced stage characterized by tumor infiltration
      of the serosa or the presence of regional lymph node metastases. Surgery alone is
      no longer the standard treatment for locally advanced gastric cancer as the
      prognosis is markedly improved by perioperative chemotherapy. The decisive factor
      for optimum treatment is the multidisciplinary team specialized in gastric
      cancer. However, despite multimodal therapy and adequate surgery only 30% of
      gastric cancer patients are alive at 3 years. This article reviewed the
      principles of the surgical management of gastric cancer (minimally invasive or
      open) and how this may optimize multimodal treatment.

PMID- 29177226
TI  - Comparative effectiveness of laparoscopic versus open prostatectomy for men with
      low-risk prostate cancer: a matched case-control study.
AB  - : Little data exist on effect of undergoing laparoscopic prostatectomy(LP) versus
      open prostatectomy(OP) upon 30-day mortality rates among low-risk prostate cancer
      patients. Materials and methods: Using the National Cancer Database, we
      identified men (2004 to 2013) with biopsy-proven, low-risk prostate cancer who
      met the eligibility criteria: N0, M0, T-stage<=2A, PSA<=10 ng/mL, and Gleason
      score=6. We utilized a 1:N matched case-control study, with cases and controls
      matched by race, insurance status, Charlson-Deyo comorbidity score, surgical
      margin status, and facility type to investigate the short-term comparative
      effectiveness of LP versus OP. Results: Among the 448,773 patients in the
      National Cancer Database with low-risk prostate cancer, 116,359 patients met the
      above inclusion criteria. The target group was restricted to patients who
      received LP or OP, thus, leaving 44,720 patients for the study. The use of LP
      (compared with OP) was associated with patients with privately insured patients,
      treatment at an academic/research centers, high-volume hospitals, and white race
      (all P<0.01). LP was less frequently utilized for black patients, those who
      received treatment at community centers, and for those with Medicaid
      insurance(all P<0.01). The odds ratio of death for surgery type (laparoscopy vs.
      open) was estimated at 0.31 (95% confidence interval, 0.135-0.701; P<0.05). Thus,
      the risk of death within 30 days was 69% lower with LP compared with OP.
      Conclusions: We found that the 30-day mortality rate among low-risk prostate
      cancer patients is significantly lower among patients who received LP when
      compared with OP, with various clinicopathologic parameters associated with its
      preferential use.

PMID- 29177227
TI  - The rising prevalence of obesity: part A: impact on public health.
AB  - Excessive fat accumulation in the body may impair health leading to a significant
      long-term health consequences including the development of diabetes, coronary
      heart disease, and osteoarthritis as well as increasing the risk of developing
      certain cancers and influencing their outcomes. England has some of the worst
      figures and trends in obesity compared with the rest of the Europe. In the
      majority of European countries the trend has increased from 10% to 40% in the
      last 10 years, whereas in England prevalence has more than doubled. This article
      outlines the public health impact of rising obesity levels.

PMID- 29177228
TI  - A systems analysis of ward rounds in plastic surgery at a single center.
AB  - : Ward rounds permeate health care delivery worldwide and form an important daily
      activity within all hospitals. In this study, the daily morning ward round in
      plastic surgery was examined from a teleological and systems point of view.
      Methods: Data were gathered from the following sources to inform the systems
      analysis: patient interviews, staff interviews, direct observations of the ward
      round on multiple occasions, and through process mapping. Results: To better
      understand the ward and its layout, a schematic of it was developed. Following
      observations of the ward round and the way in which decisions are made on it, an
      IDEF0 map was developed. Three patients were invited to take part in the study.
      Three members of staff were interviewed. The overarching themes from the
      interviews related to aspects of communication which this paper details.
      Conclusions: This small-scale study demonstrates how the ward round as a process
      can be assessed, including product quality, process quality, the measurement and
      management of capacity, the role of standardization, the role and significance of
      bottlenecks, the key information flows, including the role of feedback, and the
      motivation and incentives of system participants and ideas for improvement
      generated.

PMID- 29177230
TI  - A step forward in surgical education?

PMID- 29177229
TI  - The rising prevalence of obesity: part B-public health policy solutions.
AB  - Obesity is likely to supersede tobacco as the biggest cause of premature death.
      England has some of the worst figures and trends in obesity compared with the
      rest of the Europe. Rising obesity prevalence is an international crisis that has
      the potential to overwhelm health care resources as well as creating enormous
      human suffering and social cost. This article outlines potential public health
      policy solutions to this crisis.

PMID- 29177232
TI  - Functional rehabilitation in advanced intraoral cancer: erratum.

PMID- 29177231
TI  - Is a surgical CURE in the future for colorectal cancer liver metastasis?
AB  - This review was constructed to evaluate the current advancements in the surgical
      management of colorectal cancer liver metastases. A shift from the classic
      conservative and palliative management of such cases has begun with transitions
      toward surgical management. This shift is due to multiple compounding factors of
      which many are being studied and presented individually. By combing these factors
      together, this review provides guidance on the most significant preoperative
      prognostic factors and suggests future treatment goals for these patients. A
      progressive conversion from conservative to surgical management also presents
      ethical implications to be considered. This review may direct future research on
      surgical resection of colorectal cancer liver metastases and provide advantageous
      information on the value of preoperative prognostic factors and the role of
      surgical intervention in this patient population.

PMID- 29177233
TI  - Sulfonylureas (not metformin) improve survival of patients with diabetes and
      resectable pancreatic adenocarcinoma: erratum.

PMID- 29177234
TI  - The rising prevalence of obesity: part A: impact on public health: erratum.

PMID- 29177235
TI  - Metastatic melanoma patients' sensitivity to ipilimumab cannot be predicted by
      tumor characteristics.
AB  - : Immune checkpoint inhibitors have dramatically changed the prognosis for
      patients with metastatic melanoma. However, not all patients respond to therapy
      and toxicities can be severe leaving need for reliable clinical predictive
      markers. Methods: We examined primary tumor characteristics including ulceration,
      BRAF mutation status, and Breslow depth in patients who subsequently developed
      stage IV disease and were treated with ipilimumab at 3 institutions. Patients in
      this study were not treated on clinical trials. To investigate the relationship
      between patient characteristics at the time of diagnosis and survival following
      melanoma diagnosis we utilized Cox proportional hazards models, accounting for
      delayed entry into the study cohort. Cox models estimate the age and institution
      adjusted hazard ratios for risk of death. Results: Of patients (n=385) treated
      with ipilimumab for stage IV melanoma, 302 met inclusion criteria. The complete
      response to ipilimumab was 5%, partial response was 13%, 18% had stable disease,
      62% had progressive disease, and 5 unknown. The median overall survival rate was
      2.03 years [95% confidence interval (CI): 0.13, 3.05]. Primary tumor Breslow
      depth, lymphovascular invasion, BRAF status, and ulceration did not predict
      sensitivity to ipilimumab. In this study patient cohort, BRAF mutation (adjusted
      hazard ratio: 1.43, 95% CI: 0.98, 2.07) and presence of ulceration (adjusted
      hazard ratio: 1.47, 95% CI: 0.95, 2.26) contributed to an increased risk of
      death. Conclusions: The presence of ulceration did not correlate with sensitivity
      to ipilimumab. Ulceration of the primary tumor and a BRAF mutation were
      moderately associated with worse survival in patients with metastatic melanoma
      treated with ipilimumab.

PMID- 29177236
TI  - A new strategy and system for the ex vivo ovary perfusion and cryopreservation:
      An innovation.
AB  - Children and young adults, who suffer from cancer, receive gonadotoxic therapy,
      which destroys their fertile abilities after survival. Ovarian cryopreservation
      and transplantation provide the promising solution to this problem, where the
      ovary can be removed before the gonadotoxic therapy and reimplanted after
      patient's survival, where the ovary is to be cryopreserved during the period of
      the therapy. However, cryopreservation of the whole ovary is still facing great
      obstacles, namely the ischemic reperfusion injury and the defective
      cryopreservation related to the defective ability to universally deliver the
      cryopreservation/warming solutions through the ovarian vascular bed. Meanwhile,
      the currently applied technique of ovarian tissue cryopreservation provides
      limited follicular recovery because many follicles are lost until the development
      of revascularization post-transplantation. To solve the problems, an innovative
      system has been developed to insure immediate and universal delivery of the
      cryopreservation/warming solutions to the graft, in addition to keeping the graft
      under continuous perfusion before and after cryopreservation, minimizing any
      chance for microthrombi formation or ischemia-reperfusion. This innovative system
      can be applied in the following surgical and clinical interventions: 1)
      Allogeneic ovarian transplantation; 2) Preservation of fertility after systemic
      chemotherapy or bone marrow transplantation in young females, where the ovaries
      could be removed before the therapy and exposed to the adequate cryopreservation
      provided by the system till re-implantation after the patient's survival; 3) The
      system is also suitable for the corresponding applications on the testicles.

PMID- 29177238
TI  - Comparing the effect of gonadotropin-releasing hormone agonist and human
      chorionic gonadotropin on final oocytes for ovulation triggering among infertile
      women undergoing intrauterine insemination: An RCT.
AB  - Background: The purpose of triggering in ovulation induction is to induce the
      final maturation of oocytes and their release from the ovary for fertilization.
      Objective: The aim of the present study was to compare the effectiveness of
      gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin
      (HCG) on the final maturation of oocytes and pregnancy rates in intrauterine
      insemination (IUI) cycles. Materials and Methods: In this randomized clinical
      trial, 110 infertile women who were selected for IUI entered the study. Ovulation
      induction was performed. Group I received 0.1 mg GnRH agonist as triggering and
      group II received 10,000 IU of HCG. The serum E2, LH, and FSH levels were
      measured at 12 and 36 hr after injection. Results: LH surge was detected in all
      patients. LH levels at 12 and 36 hr after triggering was higher in Group I and it
      washed out earlier than group II (p=0.00). The pregnancy rate was higher in Group
      I, but the difference was not statistically significant (26.9% vs. 20.8%,
      respectively p=0.46). Also, the incidence of ovarian hyperstimulation syndrome
      was not different between the two groups (p=0.11). There was a significant
      difference regarding the estradiol levels at 36 hours after triggering (p=0.00).
      Conclusion: Effects of GnRH on endogenous LH surge is sufficient for oocyte
      releasing and final follicular maturation. Pregnancy rates and ovarian
      hyperstimulation syndrome incidence were not different between the groups. We
      suggest that GnRH agonists might be used as an alternative option instead of HCG
      in IUI cycles.

PMID- 29177239
TI  - Genital infections and reproductive complications associated with Trichomonas
      vaginalis, Neisseria gonorrhoeae, and Streptococcus agalactiae in women of Qom,
      central Iran.
AB  - Background: Trichomonas vaginalis (T.vaginalis) and Neisseria gonorrhoeae
      (N.gonorrhoeae) are two most common non-viral sexually transmitted infections in
      the world. No data are available regarding the epidemiology of genital infections
      in women of Qom, central Iran. Objective: Epidemiological investigation of
      sexually transmitted infections in genital specimens of women referred to the
      referral gynecology hospital in Qom, central Iran. Materials and Methods: Genital
      swab specimens were collected from women volunteers and used for identification
      of bacterial and protozoal infections by conventional microbial diagnostics, porA
      pseudo gene LightCycler(r) real-time PCR (for N.gonorrhoeae) and ITS-PCR (for
      T.vaginalis). Results: Of 420 volunteers, 277 (65.9%) had genital signs/symptoms,
      including 38.3% malodorous discharge, 37.9% dyspareunia, and 54.8% abdominal
      pain. Totally, 2 isolates of Streptococcus agalactiae were identified. Five
      specimens (1.2%) in Thayer-Martin culture and 17 (4.1%) in real-time PCR were
      identified as N.gonorrhoeae. Fifty-four specimens (12.9%) in wet mount, 64
      (15.2%) in Dorset's culture, and 81 (19.3%) in ITS-PCR showed positive results
      for T.vaginalis. Five mixed infections of T.vaginalis+ N.gonorrhoeae were found.
      The risk of T.vaginalis infection was increased in women with low-birth-weight
      (p=0.00; OR=43.29), history of abortion (p=0.00; OR=91.84), and premature rupture
      of membranes (PROM) (p=0.00; OR=21.75). The probability of finding nuclear
      leukocytes (p=0.00; OR=43.34) in vaginal smear was higher in T.vaginalis
      infection. Conclusion: The significant prevalence of trichomoniasis and gonorrhea
      emphasizes the need for accurate diagnosis and effective surveillance to prevent
      serious reproductive complications in women.

PMID- 29177240
TI  - Polycystic ovary syndrome and circulating inflammatory markers.
AB  - Background: Human and experimental studies suggest that the sympathetic
      regulatory drive in the ovary may be unbalanced (hyperactivity) in polycystic
      ovary syndrome (PCOS). Dysfunctional secretion of interleukin (IL) -1 (alpha &
      beta) or related cytokines may thus be related to abnormal ovulation and
      luteinization. Objective: The aim of this study was the evaluation of cytokines'
      pattern in PCOS women and discussion about the explanation of cross-talk between
      two super systems: sympathetic and immune systems and explanation sympatho
      excitation and relationship with interleukins. Materials and Methods: In this
      study, 171 PCOS women aged between 20-40 years were studied the. Their body mass
      index was <28. The patients were divided into two groups: study group (n=85, PCOS
      women) and control group (n=86 normal women). The blood sample was obtained on
      the 3rd day of menstruation cycle. IL-17, IL-1alpha, IL-1beta, and TNF-alpha
      concentrations were determined in both groups. Results: The median serum level of
      IL-1alpha in the PCOS group was higher than the control group (293.3 and 8.0,
      respectively, p<0.001). Also, the median serum level of IL-1beta was higher than
      the control group (5.9 and 3.1 respectively). But the median serum of level IL-17
      in women with PCOS was significantly lower than the control group (p<0.001).
      Conclusion: Our results confirm that PCOS is a low-level chronic inflammation.

PMID- 29177237
TI  - The etiologies of DNA abnormalities in male infertility: An assessment and
      review.
AB  - The sperm DNA damage may occur in testis, genital ducts, and also after
      ejaculation. Mechanisms altering chromatin remodeling are abortive apoptosis and
      oxidative stress resulting from reactive oxygen species. Three classifications of
      intratesticular, post-testicular, and external factors have been correlated with
      increased levels of human sperm DNA damage which can affect the potential of
      fertility. Lifestyle, environment, medical, and iatrogenic factors might be
      considered to cause dysmetabolism to make distracting interactions and endocrine
      disrupting compounds. As a result, these may induce chromatin/DNA alteration in
      germ cells, which may be transmitted across generations with phenotypic
      consequences. Alcohol consumption may not increase the rate of sperm residual
      histones and protamine deficiency; however, it causes an increase in the
      percentage of spermatozoa with DNA fragmentation and apoptosis. In a medical
      problem as spinal cord injury, poor semen parameters and sperm DNA damage were
      reported. Infection induces reactive oxygen species production, decreases the
      total antioxidant capacity and sperm DNA fragmentation or antigen production that
      lead to sperm dysfunctions and DNA fragmentation. While reactive oxygen species
      generation increases with age, oxidative stress may be responsible for the age
      dependent sperm DNA damage. The exposing of reproductive organs in older men to
      oxidative stress for a long time may produce more DNA-damaged spermatozoa than
      youngers. Examining the sperm chromatin quality in testicular cancer and
      Hodgkin's lymphoma patients prior to chemotherapy demonstrated the high incidence
      of DNA damage and low compaction in spermatozoa at the time of the diagnosis. In
      chemotherapy cycle with genotoxic agents in cancer patients, an increase in sperm
      DNA damage was shown after treatment. In overall, those factors occurring during
      the prenatal or the adult life alter the distribution of proteins associated with
      sperm chromatin induce changes in germ cells which can be detected in infertile
      patients.

PMID- 29177241
TI  - Effectiveness of infertility counseling on pregnancy rate in infertile patients
      undergoing assisted reproductive technologies: A systematic review and meta
      analysis.
AB  - Background: Psychological interventions such as counseling for infertile patients
      seem to increase pregnancy rate. Objective: The aim of this systematic review and
      meta-analysis was to examine if counseling improves pregnancy rate among
      infertile patients. Thus, randomized controlled trials investigating the effect
      of counseling on pregnancy rate in infertile patients undergoing ART were pooled
      in a meta-analysis. Materials and Methods: The databases of PubMed, Scopus,
      Cochrane, Google Scholar, and Persian databases including SID, Iran Medex, and
      Magiran were searched from 1997 to July 2016 to identify relevant articles.
      Included studies were trials on infertile patients (women or couples) receiving
      counseling independent of actual medical treatment. The outcome measure was
      pregnancy rate. Out of 620 relevant published trials, a total of nine RCTs were
      ultimately reviewed systematically and included in a meta-analysis to measure the
      efficacy of counseling on pregnancy rate. Odds ratio and Risk difference were
      calculated for pregnancy rate. All statistical analyses were done by
      Comprehensive Meta-analysis Version 2. Results: Nine RCTs involving 1079
      infertile women/couples were included in the study. The findings from RCTs
      indicated significant effect of counseling on pregnancy rate so that there was a
      positive impact of counseling on pregnancy rate (OR= 3.852; 95% CI: 2.492-5.956;
      p=0.00) and (RD= 0.282; 95%; CI: 0.208-0.355; p=0.00). Conclusion: Counseling was
      found to improve patients' chances of becoming pregnant. So counseling represents
      an attractive treatment option, in particular, for infertile patients who are not
      receiving medical treatments.

PMID- 29177242
TI  - In vitro development of embryos from experimentally Kerack-addicted Mice.
AB  - Background: Prenatal drug exposure, as a common public health concern, is
      associated with an increased risk of adverse effects on early embryo development.
      Objective: To investigate the in vitro development of - embryo from
      experimentally Kerack-addicted mice. Materials and Methods: Twenty-five female
      mice were studied in five groups: control, vehicle, and three experimental groups
      of Kerack-dependent mice (I, II, and III) which received different doses of
      Kerack for 14 days. After the establishment of addiction model (7 days),
      experimental groups I, II, and III were given Kerack intraperitoneally at the
      doses of 5, 35, and 70 mg/kg, twice a day for a period of 7 days, respectively.
      The vehicle group received normal saline and lemon juice whilst the control group
      just received water and food. Morulae were obtained through oviduct flashing. The
      survived embryos were cultured in T6+ 5mg/ml bovine serum albumin. The
      developmental rates up to hatched stage daily and embryo quality (differential
      staining and Tunnel staining) were also assessed. Results: The developmental
      potential of embryos obtained from the addicted mother was significantly
      decreased in comparison with control group. There was a significant reduction in
      the rate of blastocyst formation in the high dose Kerack dependent group.
      However, in addicted mice there was reduction in the total cell number (40.92%
      vs. 65.08% in control) and, inner cell mass percentage (17.17% vs. 26.15% in
      control) while apoptotic cells numbers were increased (7.17 vs. 1.46 in control)
      (p<0.05). Conclusion: The Kerack addiction during pregnancy retards
      preimplantation development and induces apoptosis.

PMID- 29177243
TI  - Association of leptin and insulin resistance in PCOS: A case-controlled study.
AB  - Background: Endocrine abnormalities related to polycystic ovary Syndrome (PCOS)
      are important problems. Objective: To compare serum leptin levels between
      infertile women with and without PCOS. To rank sensitivity of six indirect
      methods for detection of insulin resistance (IR) and to evaluate the association
      between leptin and IR in PCOS group. Materials and methods: This Case-controlled
      study performed on 189 infertile women referred to Shiraz Mother and Child
      Hospital during 2012-2015. Ninety-nine PCOS cases according to Rotterdam criteria
      were compared to 90 cases without PCOS. Serum leptin, body mass index (BMI),
      several hormones, and their correlation coefficients with leptin were compared.
      IR in PCOS women was measured by indirect methods, including fasting blood sugar
      (FBS), fasting insulin (FI), glucose/insulin, homeostatic model assessment of
      insulin resistance (HOMA-IR), quantitative insulin sensitivity check index
      (QUICKI), and MacAuley index. Association between IR and leptin was evaluated.
      Independent sample t-test and Pearson's test were used. Results: Infertile women
      with PCOS had higher BMI (26.47+/-3.62 vs. 24.82+/-5.18 kg/m2) and serum leptin
      levels (41.79+/-187.89 vs. 19.38+/-12.57 ng/mL). Leptin showed significant
      association with weight and BMI in both groups (p<0.001) and to age in non-PCOS
      group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods.
      The mean leptin levels had positive association with IR assessed by HOMA-IR
      (p<0.001), QUICKI (p<0.001), FI (p=.002), and FBS (p=0.02). Conclusion: BMI and
      IR have positive association with serum leptin in PCOS infertile women. HOMA-IR
      followed by FI and QUICKI is the most sensitive test for detection of IR.

PMID- 29177244
TI  - Final follicular maturation by administration of GnRH agonist plus HCG versus HCG
      in normal responders in ART cycles: An RCT.
AB  - Background: Gonadotropin-releasing hormone agonists (GnRH-a) was increasingly
      used for triggering oocyte maturationfor the prevention of ovarian
      hyperstimulation syndrome. Studies suggest that GnRH-a might be used as a better
      trigger agent since it causes both Luteinizing hormone and follicle stimulating
      hormone release from a physiologic natural cycle. Objective: The aim of this
      study was to evaluate the effect of dual-triggering in assisted reproductive
      technology outcomes. Materials and Methods: 192 normal responder women aged <=42
      years and 18< Body Mass Index <30 kg/m2 enrolled in this single-blind randomized
      controlled trial. All participants received antagonist protocol. For final
      triggering, women randomly were divided into two groups. Group, I was triggered
      by 6500 IU human chorionic gonadotropin (hCG) alone, and group II by 6500 IU hCG
      plus 0.2 mg of triptorelin. The implantation, chemical, clinical and ongoing
      pregnancy, and abortion rates were measured. Results: The mean of retrieved
      oocytes and obtained embryos were statistically higher in the dual-trigger group
      (group I), but the implantation and pregnancy rates were similar in two groups.
      Conclusion: The results of our study did not confirm the favorable effect of dual
      triggered oocyte maturation with a GnRH-a and a standard dosage of hCG as an
      effective strategy to optimize pregnancy outcome for normal responders in GnRH
      antagonist cycles. We think that this new concept requires more studies before
      becoming a universal controlled ovarian hyperstimulation protocol in in vitro
      fertilization practice.

PMID- 29177245
TI  - Controlled ovarian stimulation with r-FSH plus r-LH vs. HMG plus r-FSH in
      patients candidate for IVF/ICSI cycles: An RCT.
AB  - Background: Different combination of gonadotropin preparation has been introduced
      with no definite superiority of one over others in in vitro fertilization (IVF),
      but individualized regimens for each patient are needed. Objective: The aim of
      the present study was to investigate the effect of controlled ovarian stimulation
      with recombinant- follicle stimulating hormone (r-FSH) plus recombinant
      luteinizing hormone (rLH) versus human menopausal gonadotropin (HMG) plus r-FSH
      on fertility outcomes in IVF patients. Materials and Methods: This is a
      randomized clinical trial study that was performed from October 2014-April 2016
      on 140 infertile patients with a set of inclusion criteria that referred to
      infertility clinics in Vali- asr and Gandhi Hospital in Tehran. The women were
      randomly divided into two treatment groups. The first group (n=70) received rFSH
      from the second day of cycle and was added HMG in 6th day and the 2nd group
      (n=70), received rFSH from the second day of cycle and was added recombinant-LH
      in 6th day. Then ovum Pick-Up and embryo transfer were performed. In this study,
      we assessed the outcomes such as; chemical and clinical pregnancy rate, live
      birth and abortion rate. Results: Number of follicles in ovaries, total number of
      oocytes or M2 oocytes and quality of fetuses has no significant differences
      between two groups (p>0.05). Total number of fetuses were significantly higher in
      patients who received rFSH + HMG (p=0.02). Fertility outcomes consisted of: live
      birth rate, chemical pregnancy and clinical pregnancy rate were higher in rFSH +
      HMG group in comparison to rFSH +r-LH group (p<0.05). Conclusion: It seems that
      in IVF patients, HMG + rFSH used for controlled ovarian hyperstimulation have
      better effects on fertility outcomes, but in order to verify the results, it is
      recommended to implement studies on more patients.

PMID- 29177246
TI  - The effect of 24 hours delay in oocyte maturation triggering in IVF/ICSI cycles
      with antagonist protocol and not-elevated progesterone: A randomized control
      trial.
AB  - Background: The best time of final oocyte maturation triggering in assisted
      reproduction technology protocols is unknown. This time always estimated by
      combined follicular size and blood progesterone level. Objective: The aim of this
      study was evaluation of the effect of delaying oocyte maturation triggering by 24
      hr on the number of mature oocytes (MII) and other in vitro fertilization cycle
      characteristics in antagonist protocols with not-elevated progesterone (p <=1
      ng/ml). Materials and Methods: All patients' candidate for assisted reproduction
      technology underwent controlled ovarian hyperstimulation by antagonist protocol.
      When at least 3 follicles with >=18 mm diameters were seen by vaginal
      ultrasonography; blood progesterone level was measured. The patients who had
      progesterone level <=1 ng/dl entered the study. The participants' randomizations
      were done and patients were divided into two groups. In the first group, final
      oocyte maturation was done by human chorionic gonadotropin at the same day, but
      in the second group, this was performed 24 hr later. Oocytes retrieval was done
      36 hr after human chorionic gonadotropin trigger by transvaginal ultrasound
      guide. Results: Number of retrieved oocytes, mature oocytes (MII), fertilized
      oocytes (2PN), embryos formation, number of transferred embryos and embryos
      quality has not significant differences between two groups. Also, fertilization
      and implantation rate, chemical and clinical pregnancy did not differ between
      groups. Conclusion: Delaying of triggering oocyte maturation by 24 hr in
      antagonist protocol with not-elevated progesterone (progesterone <=1 ng/ml) have
      not beneficial nor harmful effect on the number of mature oocytes (MII) and other
      in vitro fertilization cycle characteristics.

PMID- 29177247
TI  - Protective effects of curcumin co-treatment in rats with establishing chronic
      variable stress on testis and reproductive hormones.
AB  - Background: Protracted and repeated exposure to chronic variable stress (CVS) may
      lead to reproductive dysfunction. It is a basic cause of male infertility.
      Curcumin (CUR) is an active fraction of turmeric that used in traditional Chinese
      medicine. CUR represents various pharmacological activities. Objective: The
      purpose of this study was to determining the effects of CUR on testis and
      testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in
      rats with establishing chronic variable stress. Materials and Methods: Twenty-one
      adult male Sprague-Dawley rats were divided into three groups: 1) control, 2) CVS
      and 3) CVS+ CUR (100 mg/kg/day dissolved in 0.5 mL of olive oil). All of the
      animals in control, CVS, and CVS+CUR groups were sacrificed after 15 days.
      Testosterone, FSH, LH, and testis damage were evaluated. Results: Significant
      changes in the normal range of testosterone, FSH, LH serum levels and
      seminiferous tubule apoptotic cells were detected in CVS group compared to the
      control rats (p=0.02). These parameters changed to a less extent in CVS+CUR
      animals compared to the CVS rats (p=0.02). Conclusion: Our findings propose that
      curcumin might have curative potential on the reproductive system function and
      its impairment. It's regulated by stress and reproductive-related hormones.

PMID- 29177248
TI  - Detection of Norepinephrine in Whole Blood via Fast Scan Cyclic Voltammetry.
AB  - Bioelectronic Medicines is an emerging field that capitalizes on minimally
      invasive technology to stimulate the autonomic nervous system in order to evoke
      therapeutic biomolecular changes at the end-organ. The goal of Bioelectronic
      Medicines is to realize both 'precision and personalized' medicine. 'Precise'
      stimulation of neural circuitry creates biomolecular changes targeted exactly
      where needed to maximize therapeutic effects while minimizing off-target changes
      associated with side-effects. The therapy is then 'personalized' by utilizing
      implanted sensors to measure the biomolecular concentrations at, or near, the end
      organ of interest and continually adjusting therapy to account for patient
      specific biological changes throughout the day. To realize the promise of
      Bioelectronic Medicines, there is a need for minimally invasive, real-time
      measurement of biomarkers associated with the effects of autonomic nerve
      stimulation to be used for continuous titration of therapy. In this study we
      examine the feasibility of using fast scan cyclic voltammetry (FSCV) to measure
      norepinephrine levels, a neurochemical relevant to end-organ function, directly
      from blood. FSCV is a well-understood method for measuring electroactive
      neurochemicals in the central nervous system with high temporal and high spatial
      resolution that has yet to be adapted to the study of the autonomic nervous
      system. The results demonstrate that while detecting the electroactive
      neurochemical norepinephrine in blood is more challenging than obtaining the same
      FSCV measurements in a buffer solution due to biofouling of the electrode, it is
      feasible to utilize a minimally invasive FSCV electrode to obtain neurochemical
      measurements in blood.

PMID- 29177250
TI  - A Visual Analytics Approach to Understanding Care Process Variation and
      Conformance.
AB  - With greater pressures of providing high-quality care at lower cost due to a
      changing financial and policy environment, the ability to understand variations
      in care delivery and associated outcomes and act upon this understanding is of
      critical importance. Building on prior work in visualizing health-care event
      sequences and in collaboration with our clinical partner, we describe our process
      in developing a multiple, coordinated visualization system that helps identify
      and analyze care processes and their conformance to existing care guidelines. We
      demonstrate our system using data of 5,784 pediatric emergency department visits
      over a 13-month period for which asthma was the primary diagnosis.

PMID- 29177249
TI  - Smyd1C Mediates CD8 T Cell Death via Regulation of Bcl2-Mediated Restriction of
      outer Mitochondrial Membrane Integrity.
AB  - The SET and Mynd domain 1 (Smyd1) locus encodes three tissue-restricted isoforms.
      Two previously characterized isoforms, Smyd1A and Smyd1B, are heart and skeletal
      muscle-restricted histone methyl transferases. Here we report that a third, non
      catalytic isoform, Smyd1C, is expressed predominantly in activated CD8 T cells.
      While Smyd1C- deficient CD8 T cells undergo activation-induced apoptosis, neither
      of two classical mechanisms activation-induced cell death nor activated cell
      autonomous death are utilized. Instead, Smyd1C accumulates within both
      mitochondria and the immunological synapse where it associates with Bcl-2, FK506
      Binding Protein 8/38 (FKBP38) and Calcineurin. This complex maintains Bcl-2
      phosphorylation, enhanced mitochondrial localization, and restricted apoptosis of
      activated CD8 T cells. We suggest that CD8 T cell death is governed, in part, by
      Smyd1C regulation of Bcl2-mediated restriction of outer mitochondrial membrane
      integrity.

PMID- 29177251
TI  - A concurrent subtractive assembly approach for identification of disease
      associated sub-metagenomes.
AB  - Comparative analysis of metagenomes can be used to detect sub-metagenomes
      (species or gene sets) that are associated with specific phenotypes (e.g., host
      status). The typical workflow is to assemble and annotate metagenomic datasets
      individually or as a whole, followed by statistical tests to identify
      differentially abundant species/genes. We previously developed subtractive
      assembly (SA), a de novo assembly approach for comparative metagenomics that
      first detects differential reads that distinguish between two groups of
      metagenomes and then only assembles these reads. Application of SA to type 2
      diabetes (T2D) microbiomes revealed new microbial genes associated with T2D. Here
      we further developed a Concurrent Subtractive Assembly (CoSA) approach, which
      uses a Wilcoxon rank-sum (WRS) test to detect k-mers that are differentially
      abundant between two groups of microbiomes (by contrast, SA only checks ratios of
      k-mer counts in one pooled sample versus the other). It then uses identified
      differential k-mers to extract reads that are likely sequenced from the sub
      metagenome with consistent abundance differences between the groups of
      microbiomes. Further, CoSA attempts to reduce the redundancy of reads (from
      abundant common species) by excluding reads containing abundant k-mers. Using
      simulated microbiome datasets and T2D datasets, we show that CoSA achieves
      strikingly better performance in detecting consistent changes than SA does, and
      it enables the detection and assembly of genomes and genes with minor abundance
      difference. A SVM classifier built upon the microbial genes detected by CoSA from
      the T2D datasets can accurately discriminates patients from healthy controls,
      with an AUC of 0.94 (10-fold cross-validation), and therefore these differential
      genes (207 genes) may serve as potential microbial marker genes for T2D.

PMID- 29177252
TI  - A volumetric conformal mapping approach for clustering white matter fibers in the
      brain.
AB  - The human brain may be considered as a genus-0 shape, topologically equivalent to
      a sphere. Various methods have been used in the past to transform the brain
      surface to that of a sphere using harmonic energy minimization methods used for
      cortical surface matching. However, very few methods have studied volumetric
      parameterization of the brain using a spherical embedding. Volumetric
      parameterization is typically used for complicated geometric problems like shape
      matching, morphing and isogeometric analysis. Using conformal mapping techniques,
      we can establish a bijective mapping between the brain and the topologically
      equivalent sphere. Our hypothesis is that shape analysis problems are simplified
      when the shape is defined in an intrinsic coordinate system. Our goal is to
      establish such a coordinate system for the brain. The efficacy of the method is
      demonstrated with a white matter clustering problem. Initial results show promise
      for future investigation in these parameterization technique and its application
      to other problems related to computational anatomy like registration and
      segmentation.

PMID- 29177253
TI  - AMP-B-SBL: An algorithm for clustered sparse signals using approximate message
      passing.
AB  - Recently, we proposed an algorithm for the single measurement vector problem
      where the underlying sparse signal has an unknown clustered pattern. The
      algorithm is essentially a sparse Bayesian learning (SBL) algorithm simplified
      via the approximate message passing (AMP) framework. Treating the cluster pattern
      is controlled via a knob that accounts for the amount of clumpiness in the
      solution. The parameter corresponding to the knob is learned using expectation
      maximization algorithm. In this paper, we provide further study by comparing the
      performance of our algorithm with other algorithms in terms of support recovery,
      mean-squared error, and an example in image reconstruction in a compressed
      sensing fashion.

PMID- 29177254
TI  - Semi-quantitative assessment of pulmonary arterial hypertension associated with
      congenital heart disease through myocardial perfusion imaging.
AB  - OBJECTIVE: The study aimed to use myocardial perfusion imaging (MPI) as a semi
      quantitative method to assess the clinical severity of pulmonary arterial
      hypertension (PAH) in patients with congenital heart disease (CHD). SUBJECTS AND
      METHODS: A total of 24 patients with PAH related to CHD (PAH-CHD) who received
      interventional or medical treatment were included. All patients underwent
      physical examination, cardiac function evaluation, biochemical test,
      echocardiography, right heart catheterization (RHC), and MPI with 99mTc
      methoxyisobutyl isonitrile (99mTc-MIBI) pre and 6 months post treatments. The
      correlation between MPI target/background (T/B) ratios and other variables were
      calculated. The receiver operating characteristic (ROC) curves were developed to
      evaluate the diagnostic value of T/B ratios. RESULTS: Most of the cardiac
      functional parameters, surplus pulse O2 (SPO2), biochemical values and right
      heart catheterization parameters were found significantly elevated after
      treatment (P<0.05). Pre-treatment MPI showed that T/B ratio had strong
      correlations with SPO2, Borg scale, cardiac output (CO), cardiac index (CI),
      right ventricular stroke volume (RV-SV), pulmonary artery pressure (PAP), total
      pulmonary resistance (TPR), total pulmonary resistance index (TPRI), pulmonary
      vascular resistance (PVR), and pulmonary vascular resistance index (PVRI). After
      6 months treatment, the correlation between T/B ratios and most of these
      parameters measured were reduced. Receiver operating characteristics curves
      showed that the diagnostic performance of MPI T/B ratio in moderate/severe PAH
      patients was significant. The area under the curve (AUC) when measured pre
      treatment was 0.929 (P=0.002) and reduced to 0.800 (P=0.046) at post-treatment.
      CONCLUSION: Semi-quantitative MPI has high diagnostic value in evaluating the
      severity level of pulmonary arterial hypertension in patients with congenital
      heart disease. The diagnostic performance of MPI at pre-treatment patients was
      superior to that at post-treatment. More cases need to be included for further
      study.

PMID- 29177255
TI  - Cell and gene therapy with reporter gene imaging in myocardial ischemia.
AB  - OBJECTIVE: Reporter gene/probe systems have proved to be reliable for monitoring
      gene/cell therapy. We sought to evaluate whether a reporter gene/probe system,
      namely the human estrogen receptor ligand binding domain (hERL)/16alpha-18F
      fluoro-17beta-estradiol (18F-FES), could be used for monitoring vascular
      endothelial growth factor (VEGF) gene expression and response to bone marrow
      mesenchymal stem cell (MSCs) therapy in ischemic heart disease. ANIMALS AND
      METHODS: Reporter gene hERL and therapeutic gene VEGF165 were linked through
      internal ribosome entry site (IRES), and then the recombinant adenovirus vector
      Adenovirus 5-hERL-IRES-VEGF (Ad5-EIV) was constructed and transfected into MSCs,
      and named Ad5-EIV-MSCs. Rat myocardial infarction was induced by coronary
      arterial branch ligature, and Ad5-EIV-MSCs were transplanted by injection into
      the peripheral myocardium, while non-transfected MSCs transplantation used as
      controls. Fluorine-18-FDG micro-PET imaging was performed to confirm myocardial
      infarction 1 day after surgery. Fluorine-18-FES micro-PET/CT images were acquired
      2 days after Ad5-EIV-MSCs transplantation. Myocardial specimens were obtained and
      stained with hematoxylin-eosin (H&E) staining to verify the myocardial
      infarction. The expression of estrogen receptor (ER) and VEGF was detected using
      immunohistochemistry (IHC). RESULTS: Rat myocardial infarction models were
      successfully produced and confirmed by H&E staining. Images of 18F-FDG PET showed
      obvious reduced or absent uptake of 18F-FDG on the infarct myocardium, while
      uniform and well-distribution on the normal myocardium. 18F-FES micro-PET/CT
      showed the tracer notable accumulated in the apical region where Ad5-EIV-MSCs
      were injected with an uptake value of 0.38+/-0.09%ID/g, which was much higher
      than that of surrounding normal myocardium with nearly no uptake of 18F-FES
      (0.10+/-0.03%ID/g, n=5, P<0.05). In the group of non-transfected MSCs, the apical
      uptake was similar to that of normal myocardium. Immunohistochemistry studies
      demonstrated positive expression of both ER and VEGF in the involved region
      accompanied by active angiogenesis. CONCLUSION: This study confirmed that
      hERL/18F-FES could be used as a reporter gene/probe system for monitoring gene
      and cell therapy in the ischemic heart disease.

PMID- 29177256
TI  - Errors in the absorbed and the administered 131I therapeutic dose in patients
      with Graves' disease. A suggested more precise technique.
AB  - OBJECTIVE: The aim of this study was to evaluate the relative error (RE) in the
      thyroid absorbed dose (TD) of iodine-131 (131I) in patients with Graves' disease
      comparing the simplified Quimby-Marinelli-Hine formula method (sQMHF) and the
      Standard Operational Procedures for dosimetry (SOPD) recommended by the European
      Association of Nuclear Medicine. PATIENTS AND METHODS: This study included 45
      patients with Graves' disease 12 men and 33 women; age 44.1+/-12.8 years. Thyroid
      mass (TM) was measured using ultrasound. Uptake of 131I (RAIU) was tested at 2, 4
      6, 24, 48-72, and 96-168h after its administration and the half-life (T1/2eff)
      and resident time (RT) of 131I were computed. According to the sQMHF, a
      prescribed TD of 75Gy required 3.7MBq/g of 131I, correction based on the RAIU24h
      and T1/2eff. Subsequently, the therapeutic TD was computed according to the SOPD
      and the RE was recorded. The data were analyzed using t-tests. RESULTS: The TM,
      RAIU24h, therapeutic TD, and RE were 36.5+/-23.9g, 0.54+/-0.14, 89.4+/-9.4Gy, and
      -0.01+/-0.02, respectively. There was a significant difference (t-value 9.84,
      P<0.01) between the prescribed and therapeutic TD because the sQMHF ignores the
      absorbed dose deposited in the thyroid during the first 24h, which is included in
      the SOPD. In addition, the RE was significantly smaller than the variable
      coefficient (VC) of the therapeutic TD (t=-39.6, P<0.01). CONCLUSION: When the
      activity of 131I was calculated using the simplified Q-M-H formula, the
      therapeutic absorbed thyroid dose was significantly higher than what was expected
      for the prescribed dose. Precision of the individualized therapeutic absorbed
      dose could be improved by computing the activity of 131I using the standard
      operational procedures for dosimetry of the EANM.

PMID- 29177257
TI  - Assessment of segmental left ventricular thickening in diabetic type II obese
      patients with normal myocardial perfusion scan.
AB  - OBJECTIVE: The aim of this study is to investigate whether gated single photo
      emission tomography (gSPET) can be used to detect subclinical left ventricular
      systolic dysfunction (LVSD) in obese diabetic type II patients. SUBJECTS AND
      METHODS: We retrospectively reviewed gSPET images of 190 patients with diabetes
      mellitus type II (DM II) (137 females and 53 males) with normal myocardial
      perfusion and normal ejection fraction (EF). Standardized twenty segment polar
      maps of thickening and motion were generated. Correlation between body mass index
      (BMI) and thickening for each segment was performed. RESULTS: Statistically
      significant results were reported in female patients including: negative
      correlation between BMI and EF (-0.19, P=0.03). End diastolic volume (EDV) also
      significantly increased with increasing BMI (0.25, P<0.01). There was also
      statistically significant negative correlation between septal thickening and BMI
      segment 15 (-0.19, P=0.02), segment 16 (-0.22, P=0.01), segment 18 (-0.20,
      P=0.01), segment 19 (-0.25, P=0.003), segment 20 (-0.2, P=0.02)]. No statistical
      significant correlation was found between thickening and BMI in male patients.
      CONCLUSION: This is the first time where thickening as measured by gSPET has been
      used to demonstrate subclinical LVSD in DM II obese patients. The relationship
      between gender and obesity on cardiovascular function and structure needs further
      investigations.

PMID- 29177258
TI  - Is 18F-FDG PET/CT a valuable diagnostic tool for verifying accelerated
      atherosclerosis secondary to diabetes mellitus on insulin in the aortic segments
      and large arteries?
AB  - OBJECTIVE: Fluorine-18 fluorodeoxylglucose positron emission tomography/computed
      tomography (18F-FDG PET/CT) has a well-established role for detection and
      quantification of atherosclerotic inflammatory disease using standardized uptake
      value (SUV) measurements. Our aim was to compare the inflammatory and macroscopic
      calcification processes of atherosclerosis in the aortic segments and large
      arteries of subjects with insulin dependent diametes mellitus (IDDM) compared to
      those of age-matched controls via 18F-FDG PET/CT. PATIENTS AND METHODS: A hundred
      and ten subjects who underwent 18F-FDG PET/CT imaging for oncological diseases
      were retrospectively studied. Fifty five were diabetics on insulin and 55 were
      age-matched controls. Average SUVmax and SUVmean for four segments of aorta and
      for common iliac arteries and femoral arteries were measured and compared between
      subject groups. Presence or absence of macroscopic calcification on CT images for
      each arterial segment was also noted and compared between these groups. RESULTS:
      Average SUVmax and SUVmean were statistically significantly greater in subjects
      with IDDM compared to controls in all arterial segments (P<=0.001). Presence of
      calcification on CT was more frequently encountered in 6 of the 8 segments in
      subjects with IDDM, and there was statistically significantly difference for the
      descending aorta and abdominal aorta. CONCLUSION: Our results show that
      inflammatory component of atherosclerosis was more severe in all aortic segments
      in subjects with IDDM compared to those of controls. Presence of macroscopic
      calcification also detected to be more frequently encountered in the descending
      thoracic and abdominal aorta in subjects with IDDM. Fluorine-18-FDG PET/CT is a
      valuable diagnostic tool for detecting and semi-quantifying accelerated
      atherosclerotic inflammatory and calcific changes secondary to diabetes mellitus
      treated with insulin in the aortic segments and large arteries.

PMID- 29177259
TI  - The influence of adipose tissue volume can significantly affect the metabolic
      activity of reference organs in 18F-FDG PET/CT studies of a normal healthy
      population.
AB  - OBJECTIVE: This study investigated whether fluorine-18-fluorodeoxyglucose (18F
      FDG) uptake of reference organs can be affected by subjects' factors in positron
      emission tomography/computed tomography (PET/CT) in a healthy population.
      SUBJECTS AND METHODS: A total of 208 normal healthy subjects without diabetes or
      dyslipidemia were included. Adipose tissue volume was measured by CT images from
      a dedicated PET/CT scan. Uptake of 18F-FDG of reference organs was measured from
      liver, blood pool, and muscle, and was normalized by lean body anthropometric
      data and adipose tissue volume. RESULTS: Of 208 participants, 118 were
      metabolically healthy lean (MHL); with body mass index (BMI) <25kg/m2 and 90 were
      metabolically healthy obese (MHO) with; BMI>=25kg/m2 . These subjects had
      significantly higher values of liver, blood pool, and muscle than did the MHL
      subjects (P<0.001 for both). Among subjects' factors, adipose tissue volume
      revealed strongest correlation with standardized uptake value multiplied by lean
      body weight divided by body weight (SUL) of liver (r=0.754, P<0.001), of blood
      pool (r=0.756, P<0.001) and of muscle (r=0.635, P<0.001). On regression analysis,
      adipose tissue volume was determined to be a common independent predictor for SUL
      of liver, blood pool and muscle (P<0.001) and furthermore was serum C-reactive
      protein level for SUL of the liver and also age and serum insulin level for SUL
      of blood pool. CONCLUSION: Adipose tissue volume can significantly affect SUL of
      liver, blood pool, and muscle in a healthy population. Liver and blood pool may
      have limited roles as reference organs for normalization of 18F-FDG uptake of the
      lesion.

PMID- 29177260
TI  - Radioiodine associated de novo Graves' opthalmopathy in an Asian cohort.
AB  - Radioactive iodine in the treatment of Graves' disease has been associated with
      the development of de novo Graves' ophthalmopathy (GO). In this report, we
      describe five individuals who required extensive ophthalmic treatment for post
      RAI de novo GO.

PMID- 29177261
TI  - Performance and safety profile of regadenoson myocardial perfusion imaging: first
      experience in Greece.
AB  - OBJECTIVE: MPI can provide valuable information in the investigation of patients
      with known or suspected coronary artery disease. The stress component of the
      studies can be conducted with regadenoson, which was approved for clinical use in
      Greece in 2016. We investigated the performance and safety profile of regadenoson
      MPI based on our 7 months institutional experience. PATIENTS AND METHODS: We
      studied 96 consecutive patients (59 males, 37 females, mean age 70.35y.o, range:
      46-87y.o.) referred to our department for a clinically indicated MPI study with
      pharmacological stress. Eleven patients suffered from chronic obstructive
      pulmonary disease. Patients underwent regadenoson stress test, combined with both
      stress and rest imaging. Data on the symptoms and electrocardiographic changes
      due to regadenoson administration were recorded. Symptoms were graded as 1-mild:
      a symptom that did not distress the patient, 2-moderate: a symptom that
      distressed the patient but it was self-limiting, or 3-severe: a symptom that
      distressed the patient requiring medical intervention. RESULTS: Regadenoson
      related symptoms were reported in 56 patients and were: dyspnea, discomfort,
      dizziness, chest pain, epigastric pain, neck pain, headache, flushing, nausea,
      heartburn, weakness, and upper limbs numbness. The severity of symptoms was
      recorded as grade 1 in 30 patients, grade 2 in 25 patients, and grade 3 in 1
      patient. Two or more different symptoms were reported in 28 patients. Ischemic
      electrocardiographic changes and arrhythmias were observed in 8 patients.
      CONCLUSION: Our findings support previously published data indicating the optimal
      safety profile of regadenoson MPI, even in the group of patients suffering from
      chronic obstructive pulmonary disease.

PMID- 29177262
TI  - Metabolic activity in bone metastases of breast and prostate cancer were similar
      as studied by 18F-FDG PET/CT. The role of 99mTc-MDP.
AB  - OBJECTIVE: The aim of this study was to compare the metabolic activity of
      metastatic foci from breast and prostate cancer patients as scanned by fluorine
      18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
      PET/CT) and by technetium-99m methyl diphosphonate (99mTc-MDP) bone scan (BS).
      SUBJECTS AND METHODS: Forty one patients were studied, divided into 2 groups
      based on histologically confirmed diagnosis: a) Breast cancer group, 23 women,
      mean age: 61+/-12 years, range: 37-79 years and, b) Prostate cancer group, 18
      men, mean age 68+/-8 years, range: 52-82 years. Another group of 17 non cancer
      atherosclerotic subjects 9 women and 8 men, of mean age and age range similar to
      the above were also studied for comparison. The R index (the total count rate in
      bone metastases divided by the total count rate in a contralateral area), the
      maximum semi-quantitative standardized uptake value (SUVmax) of BS lesions and
      the mean number of metastases were evaluated. For the metastatic findings in the
      PET/CT scans the automatic method of contouring with 50% background cut-off was
      used, while for the 99mTc-MDP BS metastases were delineated manually. RESULTS:
      The mean R index of the bone metastatic foci studied by 18F-FDG PET/CT was 1.89+/
      0.69 for Groups I and II patients. There was no significant difference of the R
      index between prostate cancer and breast cancer metastases (1.95+/-0.86 vs 1.83+/
      0.52). The average SUVmax value was significantly higher in breast cancer
      patients than in prostate cancer patients (5.15+/-2.54 vs 4.01+/-1.71; P<0.05).
      There was no significant correlation in both cancer groups between R index and
      SUVmax values. The number of metastatic foci diagnosed by the 99mTc-MDP BS scan
      was much less than by the 18F-FDG PET/CT. CONCLUSION: No significant correlation
      was noticed in the metabolic activity-glucose utilization of metastatic bone foci
      between breast and prostate cancer cases. This observation validates the
      independent value of analyzed diagnostic methods and suggests negligible
      influence of glucose utilization in bone re-modeling in the above metastatic
      cancer cells. The 18F-FDG PET/CT bone scan was much better in diagnosing
      metastases compared to the 99mTc-MDP scan.

PMID- 29177263
TI  - Primary radiation dosimetry of a novel PET radiopharmaceutical 68Ga-NODAGA
      glycine in comparison with 99mTc-DTPA in renal studies.
AB  - OBJECTIVE: In this study, we tried to estimate human absorbed dose of 68Ga-NODAGA
      glycine as a new potential positron emission tomography (PET) renal agent based
      on the biodistribution data reported in healthy rats, and compare our estimation
      with the available absorbed dose data from technetium-99m
      diethylenetriaminepentaacetic acid (99mTc-DTPA). SUBJECTS AND METHODS: The
      medical internal radiation dose (MIRD) formulation was applied to extrapolate
      from rats to human and to project the absorbed radiation dose for various organs
      in humans. S factor calculated by Monte-Carlo N-particle (MCNP) simulation and
      also this factor has been taken from the tables presented in MIRD pamphlet No.11.
      Hence, two radiation absorbed dose were calculated for organs. RESULTS: Our dose
      prediction shows that an 185MBq injection of gallium-68-1,4,7-triazacyclononane-1
      gamma-glutamylglycine-4,7-diacetic acid (68Ga-NODAGA-glycine) in humans might
      result in an estimated absorbed dose of 0.063mGy in the whole body when S factor
      calculated by MCNP simulation. The highest absorbed doses are observed in
      kidneys, lungs, spleen, liver, and red marrow with 3.510, 0.453, 0.335, 0.268,
      and 0.239mGy, respectively. In addition to, the estimated absorbed dose for total
      body after injection of 185MBq of 68Ga-NODAGA-glycine is 0.053mGy when S factor
      has been taken from MIRD pamphlet No.11. The highest absorbed doses are observed
      in kidneys, lungs, liver, spleen, and red marrow with 3.110, 0.438, 0.209, 0.203,
      and 0.203mGy, respectively. Comparison between human absorbed dose estimation for
      68Ga-NODAGA-glycine and 99mTc-DTPA indicated that the absorbed dose of the most
      organs after injection of 99mTc-DTPA is higher than the amount after 68Ga-NODAGA
      glycine. CONCLUSION: The results showed that 68Ga-NODAGA-glycine delivers lower
      dose to the patients. Also due to its application in PET (which offers higher
      sensitivity and spatial resolution compared to planar or SPET), 68Ga-NODAGA
      glycine would be a superior choice than 99mTc-DTPA for renography and impose less
      radiation doses to patients.

PMID- 29177264
TI  - Results of performing or not cardiac resynchronization therapy for live
      assessment of LV function and mechanical systole synchrony using gated myocardial
      perfusion imaging and real-time three-dimensional echocardiography. Seven months
      follow-up.
AB  - We studied a 50 years old male patient who underwent cardiac resynchronization
      therapy on and off (CRT-on and CRT-off) for assessment of left ventricular (LV)
      function and mechanical systole synchrony using gated myocardial perfusion
      imaging (gMPI) and real-time three-dimensional echocardiography (RT3DE). The
      patient was reexamined after seven months. The comparison of these two modalities
      showed consistent results on assessing both the CRT-on and CRT-off conditions.
      This result may indicate that an immediate synchronization parameter change
      during CRT-on may be valuable for predicting response to CRT surgery.

PMID- 29177265
TI  - Metastatic melanoma response to combination therapy with ipilimumab and
      vemurafenib.
AB  - Combination therapies for the treatment of metastatic melanoma are a matter of
      debate nowadays. We report on a stage IV metastatic melanoma patient with the
      BRAF V600 mutation and a large tumor burden initially treated with two cycles of
      ipilimumab. Due to dramatic disease progression, demonstrated on interim 18F-FDG
      PET/CT, vemurafenib was added in the patient's therapeutical scheme. After
      completion of the concurrent ipilimumab and vemurafenib administration, a third
      18F-FDG PET/CT showed an impressive metabolic remission of the metastatic
      disease, reflecting the potential role of the modality in treatment response
      evaluation of melanoma patients receiving combination therapies.

PMID- 29177266
TI  - Atypical Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis
      simulating lymphadenitis on 18F-FDG PET/CT and its differential diagnosis.
AB  - Diagnosis of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis
      (EBV-HLH) is challenging as its clinical presentation is atypical. Here we
      present a case of atypical EBV-HLH simulating lymphadenitis on fluorrine-18
      fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
      PET/CT), with a view to consider this kind of EBV-HLH as a possible differential
      diagnosis in lymphadenitis. A 68 years old male who had episodic fever
      accompanied by weight loss and weakness for two weeks was studied. Finally,
      biopsies in bone marrow and spleen revealed hemophagocytic cells. He was
      diagnosed with EBV-HLH and treated with etoposide and prednisone. His condition
      started improving soon, and his abnormal laboratory findings were normalized at
      day 15. He remained in good clinical condition at 3 months follow-up after
      hospital discharge.

PMID- 29177267
TI  - Primary and secondary hyperparathyroidism among vitamin D deficient Hashimoto's
      thyroiditis patients and the need for a parathyroid scan.
AB  - The patients with Hashimoto thyroiditis must be investigated mainly for secondary
      hyperparathyroidism due to vitamin D deficiency/insufficiency. Parathyroid
      scintigraphy has no place in the diagnosis of primary, secondary or tertiary
      hyperparathyroidism or in the decision for surgical treatment. Parathyroid
      scintigraphy is a useful preoperative technique for the localization of the
      pathological parathyroid glands.

PMID- 29177268
TI  - Advanced manufacturing of microdisk vaccines for uniform control of material
      properties and immune cell function.
AB  - The continued challenges facing vaccines in infectious disease and cancer
      highlight a need for better control over the features of vaccines and the
      responses they generate. Biomaterials offer unique advantages to achieve this
      goal through features such as controlled release and co-delivery of antigens and
      adjuvants. However, many synthesis strategies lead to particles with
      heterogeneity in diameter, shape, loading level, or other properties. In
      contrast, advanced manufacturing techniques allow precision control of material
      properties at the micro- and nano-scale. These capabilities in vaccines and
      immunotherapies could allow more rational design to speed efficient design and
      clinical translation. Here we employed soft lithography to generate polymer
      microdisk vaccines with uniform structures and tunable compositions of vaccine
      antigens and toll like receptor agonists (TLRas) that serve as molecular
      adjuvants. Compared to conventional PLGA particles formed by emulsion, microdisks
      provided a dramatic improvement in the consistency of properties such as
      diameter. During culture with primary dendritic cells (DCs) from mice, microdisks
      were internalized by the cells without toxicity, while promoting co-delivery of
      antigen and TLRa to the same cell. Analysis of DC surface activation markers by
      flow cytometry revealed microdisk vaccines activated dendritic cells in a manner
      that depended on the level of TLRa, while antigen processing and presentation
      depended on the amount of antigen in the microdisks. Together, this work
      demonstrates the use of advanced manufacturing techniques to produce uniform
      vaccines that direct DC function depending on the composition in the disks.

PMID- 29177269
TI  - A multifunctional logic gate by means of a triple-chromophore fluorescent
      biothiol probe with diverse fluorescence signal patterns.
AB  - A novel multifunctional logic gate based on a triple-chromophore (coumarin-NBD
      flavylium, CNF) fluorescent biothiol probe with diverse fluorescence signal
      patterns was rationally designed and synthetized. On the new triad CNF, diverse
      logic operations such as OR, TRANSFER, INH, NOT, and YES logic gates were
      achieved by using biothiols and fluorescence signal patterns as the multiple
      inputs and outputs, respectively.

PMID- 29177270
TI  - Assembly of protonated mesoporous carbon nitrides with co-catalytic [Mo3S13]2-
      clusters for photocatalytic hydrogen production.
AB  - The photocatalytic activity of protonated ordered mesoporous carbon nitride (pom
      CN) was significantly improved by assembling anionic [Mo3S13]2- clusters as
      cocatalysts onto the surface and channel of pom-CN via electrostatic
      interactions. This work demonstrates the feasibility of employing solution
      chemistry to assemble co-catalysts in the form of ionic clusters as building
      blocks into a photosynthetic architecture.

PMID- 29177271
TI  - f-Block complexes of a m-terphenyl dithiocarboxylate ligand.
AB  - Straightforward syntheses are provided for the m-terphenyl dithiocarboxylic acid
      2,6-(C6H4-4-tBu)2C6H3CS2H (TerphCS2H, 2) and its lithium and potassium salts,
      TerphCS2Li(Et2O)2 and TerphCS2K (1.Et2O and 4, respectively). These compounds can
      be isolated in good yields on multi-gram scales starting from Terph-I without
      isolating intermediates. Salt metathesis and protonolysis reactions provided
      access to the homoleptic actinide(iv) complexes (TerphCS2)4An (An = Th (5) and U
      (6)). Electrochemical and reactivity studies revealed that the dithiocarboxylate
      ligand is incompatible with U(iii). The homoleptic lanthanum(iii) complex
      (TerphCS2)3La and its eta6-toluene adduct (7 and 7.tol, respectively) were also
      structurally characterized. Binding of toluene to 7 was shown to displace
      intramolecular La-Carene close contacts that are facilitated by a distortion from
      the usual geometry of bound dithiocarboxylate ligands.

PMID- 29177272
TI  - Luminescent cadmium(ii) coordination polymers of 1,2,4,5-tetrakis(4
      pyridylvinyl)benzene used as efficient multi-responsive sensors for toxic metal
      ions in water.
AB  - Reactions of Cd(NO3)2.4H2O with 1,2,4,5-tetrakis(4-pyridylvinyl)benzene (4-tkpvb)
      and 5-tert-butylisophthalic acid (5-tert-H2BIPA), 1,3,5-benzenetricarboxylic acid
      (1,3,5-H3BTC) or 1,4-naphthalenedicarboxylic acid (1,4-H2NDC) under solvothermal
      conditions afforded three two-dimensional (2D) Cd(ii) coordination polymers [Cd(4
      tkpvb)(5-tert-BIPA)]n (1), [{Cd(4-tkpvb)(1,3,5-HBTC)}.0.5DMF]n (2) and [Cd(4
      tkpvb)(1,4-NDC)]n (3). Compounds 1-3 were structurally characterized by IR,
      elemental analysis, powder X-ray diffraction, and single crystal X-ray
      diffraction. Compounds 1-3 possess unique 2D networks in which 1D double chains
      [Cd2L2]n (L = 5-tert-BIPA or 1,3,5-HBTC) (1-2) or 1D linear chains [Cd(1,4-NDC)]n
      (3) are linked by 4-tkpvb ligands. Upon UV light excitation, a 4-tkpvb solution
      in DMF showed an emission band centered at 446 nm with a shoulder at 475 nm. The
      addition of Hg2+ ions into the 4-tkpvb solution in DMF remarkably changed its
      colour from colourless to yellow under natural light, or from blue to grey yellow
      under UV light, which were clearly visible to the naked eye. Compounds 1-3
      suspended in water could emit yellow-green light under UV light irradiation. The
      representative compound 1 was confirmed to be an uncommon multi-responsive
      luminescent sensor for Hg2+, CrO42- and Cr2O72- ions in water by the luminescence
      quenching method. The detection limits for these species were 0.15 MUM (Hg2+),
      0.08 MUM (CrO42-) and 0.12 MUM (Cr2O72-), respectively. The luminescence
      quenching mechanism studies revealed that these quenching processes were involved
      in either the interaction of Hg2+ with free pyridyl groups in 1 or the overlap
      between the absorption band of CrO42- or Cr2O72- and the excitation and/or
      emission bands of 1.

PMID- 29177273
TI  - Thermally induced N-S bond insertion reaction of diazo compounds with N
      sulfenylsuccinimides: synthesis of sulfides and mechanism studies.
AB  - A metal-free gem-functionalization reaction of diazo compounds with N
      sulfenylsuccinimides via a formal N-S bond insertion process has been reported.
      The transformation features mild reaction conditions, broad substrate scope and
      functional group tolerance, offering an efficient approach to sulfide synthesis
      in moderate to high yields. In addition, the mechanism studies indicate the
      formation of free carbene under thermal conditions followed by ylide generation,
      then N-S bond cleavage and C-N bond formation occurred in sequence to give the
      sulfide products.

PMID- 29177274
TI  - Synthesis of 4-substituted pyrazole-3,5-diamines via Suzuki-Miyaura coupling and
      iron-catalyzed reduction.
AB  - A general and efficient synthesis of 4-substituted-1H-pyrazole-3,5-diamines was
      developed to access derivatives with an aryl, heteroaryl, or styryl group, which
      are otherwise relatively difficult to prepare. The first step is based on the
      Suzuki-Miyaura cross-coupling reaction utilizing the XPhos Pd G2 precatalyst. The
      coupling reactions of 4-bromo-3,5-dinitro-1H-pyrazole with the electron
      rich/deficient or sterically demanding boronic acids enabled the production of
      the corresponding dinitropyrazoles. The subsequent iron-catalyzed reduction of
      both nitro groups with hydrazine hydrate accomplished the synthesis. The
      additional demethylation of the 4-methoxystyryl derivative allowed the production
      of the carboanalog of CAN508 reported as a selective CDK9 inhibitor.

PMID- 29177275
TI  - Fundamental properties and practical applications of ionic liquids: concluding
      remarks.
AB  - The Faraday Discussion on Ionic Liquids: From Fundamental Properties to Practical
      Applications took place in Cambridge in September 2017. Fundamental understanding
      of behaviour of liquids in the bulk and at surfaces was the primary emphasis of
      most of the talks, although applications were the motivation for the selection of
      many of the research projects. However, the conference almost entirely omitted
      discussion of the potential role of ionic liquids in green chemistry. Although
      initial claims of ionic liquids (ILs) being green were overstated, the search for
      green ionic liquids is still very much a worthwhile endeavour. Some confusion in
      the field has been caused by an overemphasis on the environmental impacts of ILs
      themselves, despite the fact that the manufacture of ILs causes greater impacts.
      Additional confusion has arisen from the mistaken use of the ready
      biodegradability test as an indicator for ultimate degradation. Because some ILs
      contain cores that are highly resistant to degradation, the ready
      biodegradability test can give a false positive result. The author offers
      suggestions as to how to tackle the problem of searching for greener ILs,
      including a greater focus on the impacts of the synthetic pathways of relevant
      ions. The final decision of whether an IL is green can only come from an
      application-specific life cycle assessment of a product or process using the IL
      compared to the same product/process using competing liquids.

PMID- 29177277
TI  - Path-integral simulation of graphene monolayers under tensile stress.
AB  - Finite-temperature properties of graphene monolayers under tensile stress have
      been studied by path-integral molecular dynamics (PIMD) simulations. This method
      allows one to consider the quantization of vibrational modes in these crystalline
      membranes and to analyze the influence of anharmonic effects on the membrane
      properties. Quantum nuclear effects turn out to be appreciable on the structural
      and thermodynamic properties of graphene at low temperature, and they can even be
      noticeable at room temperature. Such quantum effects become more relevant as the
      applied stress is increased, mainly for properties related to out-of-plane atomic
      vibrations. The relevance of quantum dynamics in the out-of-plane motion depends
      on the system size, and is enhanced by tensile stress. For applied tensile
      stresses, we analyze the contribution of the elastic energy to the internal
      energy of graphene. Results of PIMD simulations are compared with calculations
      based on a harmonic approximation for the vibrational modes of the graphene
      lattice. This approximation describes rather well the structural properties of
      graphene, provided that the frequencies of ZA (flexural) acoustic modes in the
      transverse direction include a pressure-dependent correction.

PMID- 29177276
TI  - Automated glycan assembly of galactosylated xyloglucan oligosaccharides and their
      recognition by plant cell wall glycan-directed antibodies.
AB  - We report the automated glycan assembly of oligosaccharides related to the plant
      cell wall hemicellulosic polysaccharide xyloglucan. The synthesis of
      galactosylated xyloglucan oligosaccharides was enabled by introducing p
      methoxybenzyl (PMB) as a temporary protecting group for automated glycan
      assembly. The generated oligosaccharides were printed as microarrays, and the
      binding of a collection of xyloglucan-directed monoclonal antibodies (mAbs) to
      the oligosaccharides was assessed. We also demonstrated that the printed glycans
      can be further enzymatically modified while appended to the microarray surface by
      Arabidopsis thaliana xyloglucan xylosyltransferase 2 (AtXXT2).

PMID- 29177278
TI  - Insight into Eu redox and Pr3+ 5d emission in KSrPO4 by VRBE scheme construction.
AB  - A series of Ln-doped KSrPO4 (Ln = Ce3+, Eu3+, Eu2+, Pr3+) phosphors are prepared
      through a high-temperature solid-state method. The KSrPO4 compound is confirmed
      to possess a beta-K2SO4 structure with the Pnma group by Rietveld refinement, and
      the temperature-dependent lattice parameters are investigated with the powder X
      ray diffraction results at different temperatures. Ce3+ and Eu3+ ions are
      introduced to probe the crystal field strength (CFS) and the lanthanide site
      symmetry by using VUV-UV-vis spectroscopy. The temperature-dependent luminescence
      properties of KSrPO4: Ce3+/Eu2+ exhibit an excellent thermal stability of
      Ce3+/Eu2+ luminescence. Based on the VUV-UV-vis spectra of Ce3+ and Eu3+ doped
      KSrPO4, the vacuum referred binding energy (VRBE) scheme is constructed to
      understand the redox properties of Eu, the 5d energy levels of Pr3+ and the
      thermal quenching characteristics of Ce3+ and Eu2+ luminescence.

PMID- 29177279
TI  - Study of Ce-Cu mixed oxide catalysts by in situ electrical conductivity
      measurements.
AB  - Three Ce-Cu mixed oxides, namely Ce0.95Cu0.05, Ce0.6Cu0.4 and Ce0.15Cu0.85, along
      with pure CeO2 and CuO were characterized by in situ electrical conductivity
      measurements. Their electrical conductivity was studied as a function of
      temperature and oxygen partial pressure, and was followed with time during
      successive exposure to air, nitrogen and different gaseous mixtures containing
      propane as a VOC model molecule, under conditions close to those of their
      catalytic applications. CeO2 and CuO appeared to be n-type and p-type
      semiconductors, respectively, while the semiconducting behavior of the Ce-Cu
      mixed oxides depended on the oxide composition. The semiconductive and redox
      properties of the samples were correlated with their catalytic behavior in CO
      oxidation, ethene total oxidation and soot combustion.

PMID- 29177280
TI  - A computational investigation of the solvent-dependent enantioselective
      intramolecular Morita-Baylis-Hillman reaction of enones.
AB  - The intramolecular Morita-Baylis-Hillman reaction of beta-mono and beta,beta
      disubstituted enones shows high yields and stereo-selective products when the
      reaction is performed in the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)
      as a solvent. In this work, we carried out a computational study using the
      density functional Becke 3-(B3) parameter exchange and the Lee-Yang-Parr (LYP)
      correlation functional and 6-31+G* basis set. Two major steps i.e. C-C bond
      formation and proton transfer were analysed using different pathways. The
      calculations show a very low barrier (DeltaG? = 0.23 kcal mol-1) for C-C bond
      formation in the case of an experimentally dominant product. For this pathway the
      subsequent proton transfer via the HFIP step has a barrier of 26.98 kcal mol-1.
      The same has been confirmed using a Molecular Electrostatic Potential (MESP),
      which shows a negative region in between CC in the transition state. In spite of
      high barriers for proton transfer, the intermediate products formed in this
      reaction pathway are thermodynamically more stable in comparison with other
      pathways. The thermodynamic stability of the final product in this pathway is
      observed to surpass all other effects in the presence of HFIP, thereby
      corroborating the experimentally observed enantioselectivity.

PMID- 29177281
TI  - The development of ruthenium(ii) polypyridyl complexes and conjugates for in
      vitro cellular and in vivo applications.
AB  - Ruthenium(ii) [Ru(ii)] polypyridyl complexes have been the focus of intense
      investigations since work began exploring their supramolecular interactions with
      DNA. In recent years, there have been considerable efforts to translate this
      solution-based research into a biological environment with the intention of
      developing new classes of probes, luminescent imaging agents, therapeutics and
      theranostics. In only 10 years the field has expanded with diverse applications
      for these complexes as imaging agents and promising candidates for therapeutics.
      In light of these efforts this review exclusively focuses on the developments of
      these complexes in biological systems, both in cells and in vivo, and hopes to
      communicate to readers the diversity of applications within which these complexes
      have found use, as well as new insights gained along the way and challenges that
      researchers in this field still face.

PMID- 29177282
TI  - Dense monolayer films of atomically precise graphene nanoribbons on metallic
      substrates enabled by direct contact transfer of molecular precursors.
AB  - Atomically precise graphene nanoribbons (GNRs) of two types, chevron GNRs and N =
      7 straight armchair GNRs (7-AGNRs), have been synthesized through a direct
      contact transfer (DCT) of molecular precursors on Au(111) and gradual annealing.
      This method provides an alternative to the conventional approach for the
      deposition of molecules on surfaces by sublimation and simplifies preparation of
      dense monolayer films of GNRs. The DCT method allows deposition of molecules on a
      surface in their original state and then studying their gradual transformation to
      polymers to GNRs by scanning tunneling microscopy (STM) upon annealing. We
      performed STM characterization of the precursors of chevron GNRs and 7-AGNRs, and
      demonstrate that the assemblies of the intermediates of the GNR synthesis are
      stabilized by pi-pi interactions. This conclusion was supported by the density
      functional theory calculations. The resulting monolayer films of GNRs have
      sufficient coverage and density of nanoribbons for ex situ characterization by
      spectroscopic methods, such as Raman spectroscopy, and may prove useful for the
      future GNR device studies.

PMID- 29177284
TI  - Fluorescence light-up detection of cyanide in water based on cyclization reaction
      followed by ESIPT and AIEE.
AB  - Schiff base 1 (2,4-di-tert-butyl-6-((2-hydroxyphenyl-imino)-methyl)phenol)
      containing two hydroxyl groups could undergo an oxidative cyclization reaction
      and then generate hydroxyphenylbenzoxazole (HBO) 2 when CN- was present as a
      catalyst. The multistep cyclization reaction was proved by spectroscopy, 1H NMR,
      13C NMR and mass spectra. C[double bond, length as m-dash]N isomerization is the
      predominant decay process of the excited states, so sensor 1 is weakly emissive
      in solution at ambient temperature. When 1 reacts with CN-, the emission is
      remarkably enhanced, where 1 is converted to 2. The cyclization product HBO 2
      displays bright green luminescence in micellar due to the ESIPT (excited-state
      intramolecular proton transfer) as well as AIEE (aggregation-induced emission
      enhancement) effect. The detection limit is 5.92 * 10-7 M, lower than the WHO
      guideline of CN- in drinking water (1.9 MUM). The selective and competitive
      experiments reveal that sensor 1 shows high sensing selectivity and sensitivity
      for CN- over other anions. Test papers containing absorbed 1 were prepared and
      applied for practical application of cyanide detection.

PMID- 29177283
TI  - A new class of dual responsive self-healable hydrogels based on a core
      crosslinked ionic block copolymer micelle prepared via RAFT polymerization and
      Diels-Alder "click" chemistry.
AB  - Amphiphilic diblock copolymers of poly(furfuryl methacrylate) (PFMA) with
      cationic poly(2-(methacryloyloxy)ethyltrimethyl ammonium chloride) (PFMA-b-PMTAC)
      and anionic poly(sodium 4-vinylbenzenesulfonate) (PFMA-b-PSS) were prepared via
      reversible addition fragmentation chain-transfer (RAFT) polymerization by using
      PFMA as a macro-RAFT agent. The formation of the block copolymer was confirmed by
      FTIR and 1H NMR analyses. In water, the amphiphilic diblock copolymers, (PFMA-b
      PMTAC) and (PFMA-b-PSS), formed micelles with PFMA in the core and the rest of
      the hydrophilic polymers like PMTAC and PSS in the corona. The PFMA core was
      crosslinked by using Diels-Alder (DA) "Click" chemistry in water at 60  degrees C
      where bismaleimide acted as a crosslinker. Afterwards, both the core crosslinked
      micelles were mixed at an almost equal charge ratio which was determined by zeta
      potential analysis to prepare the self-assembled hydrogel. The de-crosslinking of
      the hydrophobic PFMA core in the self-assembled hydrogel via rDA reaction took
      place at 165  degrees C as determined from DSC analysis. This hydrogel showed
      self-healing behavior using ionic interaction (in the presence of water) and DA
      chemistry (in the presence of heat).

PMID- 29177285
TI  - Investigations on structural determination of semi-transition-metal borides.
AB  - Lack of systematic investigations on their dynamical and energetic stability
      preclude the full understanding of the structural determination and the
      corresponding mechanical properties for the semi-transition-metal borides
      epsilon2B (epsilon = Ti, V, Cr, Mn, Fe, Co, Ni, Nb, Mo, Ta, and W). The present
      energetic calculations show nu2B (nu = Ti, V, Cr, Nb, Mo, Ta and W) with the long
      assumed I4/mcm symmetry are dynamically unstable, stemming from the large volume
      required to accommodate the boron atom at equilibrium. By freezing the unstable
      phonon mode, I4/m structure is predicted to be both energetically and dynamically
      stable. The structural stabilities for these compounds at finite temperature have
      been identified by the calculated Gibbs free energies and ab initio molecular
      dynamic simulation.

PMID- 29177286
TI  - Theoretical aspects of femtosecond double-pump single-molecule spectroscopy. I.
      Weak-field regime.
AB  - We present a theoretical description of double-pump femtosecond single-molecule
      signals with fluorescence detection. We simulate these signals in the weak-field
      regime for a model mimicking a chromophore with a Franck-Condon-active
      vibrational mode. We establish several signatures of these signals which are
      characteristic for the weak-field regime. The signatures include the quenching of
      vibrational beatings by electronic dephasing and a pronounced tilt of the phase
      time profiles in the two-dimensional (2D) maps. We study how environment-induced
      slow modulations of the electronic dephasing and relevant chromophore parameters
      (electronic energy, orientation, vibrational frequency and relative shift of the
      potential energy surfaces) affect the signals.

PMID- 29177287
TI  - All-gas-phase synthesis of amino-functionalized UiO-66 thin films.
AB  - Thin films of metal-organic frameworks (MOFs) prepared using all-gas-phase
      techniques such as atomic/molecular layer deposition (ALD/MLD) are emerging due
      to their potential for enabling suitable applications. Their high and specific
      porosity enables their use as membranes for separations and as a basis for
      sensors in microelectronics, provided that films can be made. The properties of
      such MOF materials can be tuned by choosing linker molecules that are
      functionalized with a variety of chemical groups. However, thin films of these
      functionalised MOFs have so far been prepared through wet based chemistries,
      which are difficult to combine with microelectronics and high aspect ratio
      structures. We here report on the thin film deposition of amino-functionalised
      UiO-66 through an all-gas-phase ALD/MLD process. By using amino-functionalised
      linkers, modulation by acetic acid to control the stoichiometry of the deposited
      film was no longer required, as opposed to the case in which unmodified
      terephthalic acid was used as a linker. The growth and properties of the films
      were characterised using an in situ quartz crystal microbalance (QCM),
      spectroscopic ellipsometry (SE), grazing incidence X-ray diffraction (GIXRD),
      Fourier transform infrared spectroscopy (FTIR) and other techniques to obtain
      information on their growth dynamics and physical properties.

PMID- 29177288
TI  - Rational one-step synthesis of porous PtPdRu nanodendrites for ethanol oxidation
      reaction with a superior tolerance for CO-poisoning.
AB  - Precise fabrication of porous ternary Pt-based nanodendrites is very important
      for electrochemical energy conversion owing to high surface area and great
      molecular accessibility of these nanodendrites. Herein, PtPdRu porous
      nanodendrites (PNDs) were prepared via a facile one-step ultrasonic irradiation
      approach at room temperature. Intriguingly, the ultrasonic irradiation drove the
      formation of PtPdRu PNDs with spatially interconnected porous structures, whereas
      magnetic stirring produced PtPdRu nanoflowers (NFs) with less porosity. The
      formation mechanism was ascribed to the acoustic cavitation effect and fast
      reduction kinetics under sonication. The as-made PtPdRu PNDs displayed a superior
      catalytic performance towards ethanol oxidation reaction with a high tolerance
      for CO-poisoning as compared to PtPdRu NFs, PtPd NDs, and commercial Pt/C
      catalyst.

PMID- 29177289
TI  - Double anisotropic electrically conductive flexible Janus-typed membranes.
AB  - Novel type III anisotropic conductive films (ACFs), namely flexible Janus-typed
      membranes, were proposed, designed and fabricated for the first time. Flexible
      Janus-typed membranes composed of ordered Janus nanobelts were constructed by
      electrospinning, which simultaneously possess fluorescence and double
      electrically conductive anisotropy. For the fabrication of the Janus-typed
      membrane, Janus nanobelts comprising a conductive side and an insulative
      fluorescent side were primarily fabricated, and then the Janus nanobelts are
      arranged into parallel arrays using an aluminum rotary drum as the collector to
      obtain a single anisotropically conductive film. Subsequently, a secondary
      electrospinning process was applied to the as-prepared single anisotropically
      conductive films to acquire the final Janus-typed membrane. For this Janus-typed
      membrane, namely its left-to-right structure, anisotropic electrical conduction
      synchronously exists on both sides, and furthermore, the two electrically
      conductive directions are perpendicular. By modulating the amount of Eu(BA)3phen
      complex and conducting polyaniline (PANI), the characteristics and intensity of
      the fluorescence-electricity dual-function in the membrane can be tuned. The high
      integration of this peculiar Janus-typed membrane with simultaneous double
      electrically conductive anisotropy-fluorescent dual-functionality is successfully
      realized in this study. This design philosophy and preparative technique will
      provide support for the design and construction of new types of special
      nanostructures with multi-functionality.

PMID- 29177290
TI  - Rubber contact mechanics: adhesion, friction and leakage of seals.
AB  - We study the adhesion, friction and leak rate of seals for four different
      elastomers: Acrylonitrile Butadiene Rubber (NBR), Ethylene Propylene Diene
      (EPDM), Polyepichlorohydrin (GECO) and Polydimethylsiloxane (PDMS). Adhesion
      between smooth clean glass balls and all the elastomers is studied both in the
      dry state and in water. In water, adhesion is observed for the NBR and PDMS
      elastomers, but not for the EPDM and GECO elastomers, which we attribute to the
      differences in surface energy and dewetting. The leakage of water is studied with
      rubber square-ring seals squeezed against sandblasted glass surfaces. Here we
      observe a strongly non-linear dependence of the leak rate on the water pressure
      DeltaP for the elastomers exhibiting adhesion in water, while the leak rate
      depends nearly linearly on DeltaP for the other elastomers. We attribute the non
      linearity to some adhesion-related phenomena, such as dewetting or the (time
      dependent) formation of gas bubbles, which blocks fluid flow channels. Finally,
      rubber friction is studied at low sliding speeds using smooth glass and
      sandblasted glass as substrates, both in the dry state and in water. The measured
      friction coefficients are compared to theory, and the origin of the frictional
      shear stress acting in the area of real contact is discussed. The NBR rubber,
      which exhibits the strongest adhesion both in the dry state and in water, also
      shows the highest friction both in the dry state and in water.

PMID- 29177291
TI  - The structure and catalytic properties of Rh-doped CeO2 catalysts.
AB  - The average structure and the local structure of nanocrystalline Rh-doped CeO2
      catalysts, prepared using a co-precipitation method, were studied using a set of
      structural (PDF, HRTEM, XRD) and spectral (XPS, Raman spectroscopy) methods. The
      samples with Rh content less than 10 wt%, calcined at 450  degrees C, were
      homogeneous solid solutions. A comparison of the experimental results and Pair
      distribution function (PDF) modeling data showed that Rh3+ substitutes Ce4+ ions
      in the fluorite phase. Charge equilibrium is obtained by the oxygen vacancy for
      each Rh3+ cation introduced into the ceria cell. The solid solution demonstrated
      high catalytic activity in low-temperature CO oxidation (LTO CO). The solid
      solutions were stable only in a nanocrystalline state and decomposed upon thermal
      treatment. The calcination of the solid solution at T > 450  degrees C results in
      a decrease in the catalytic activity that is accompanied by Rh association in the
      subsurface area and strong distortion of the anionic subcell. At T = 800  degrees
      C alpha-Rh2O3 nanoparticles are formed on the surface of the fluorite phase. The
      XRD-detectable Rh oxide phases are formed after calcination at 1000  degrees C.
      However, some parts of Rh within the subsurface RhxCe1-xO2-delta solid solution
      remain and they preserve catalytic properties for low-temperature oxidation.

PMID- 29177292
TI  - Tuning the luminescence of two 3d-4f metal-organic frameworks for the fast
      response and highly selective detection of aniline.
AB  - Two 3D solvent-stable zinc(ii)-lanthanide(iii) heterometallic metal-organic
      frameworks (MOFs) {[(CH3)2NH2]2[Zn2Ln2(FDA)6(DMF)2].2DMF}n [Ln = Eu (Zn-Eu) and
      Tb (Zn-Tb); H2FDA = furan-2,5-dicarboxylic acid] based on Zn2Ln2(COO)10
      tetrametallic clusters and furan-2,5-dicarboxylic acid have been successfully
      synthesized. These MOFs can serve as luminescent sensors for the fast response
      and highly selective detection of aniline via luminescence quenching. More
      importantly, a linear correlation is observed between their luminescence and the
      low concentration of aniline and the detection limits of aniline are 7.5 MUmol L
      1 for Zn-Eu and 5.2 MUmol L-1 for Zn-Tb.

PMID- 29177293
TI  - Prolonged bioluminescence imaging in living cells and mice using novel pro
      substrates for Renilla luciferase.
AB  - The prodrug or caged-luciferin strategy affords an excellent platform for
      persistent bioluminescence imaging. In the current work, we designed and
      synthesized ten novel pro-substrates for Renilla luciferase by introducing ester
      protecting groups of different sizes into the carbonyl group of the free
      luciferin 1. Taking advantage of intracellular esterases, lipases, and
      nucleophilic substances, the ester protecting groups were hydrolyzed, resulting
      in the release of a free luciferin and a bioluminescence signal turn-on. Among
      the tested pro-substrates, the butyryloxymethyl luciferin 7 exhibited low
      cytotoxicity and a prolonged luminescence signal both in cellulo and in vivo.
      Therefore, the butyryloxymethyl luciferin 7 can act as a promising substrate for
      noninvasive extended imaging in diagnostic and therapeutic fields.

PMID- 29177294
TI  - Elucidating the stability of bolaamphiphilic polypeptide nanosheets using
      atomistic molecular dynamics.
AB  - Atomistic molecular dynamics was employed to characterize the stability of
      nanosheets formed by bolaamphiphilic polypeptides. Two different nanosheets
      (based on RFL4FR and EFL4FE peptide sequences) were simulated to quantify the
      impact of the bolaamphiphilic nature of the peptides on the structure and
      energetics of the formed nanostructures. Our results corroborate the structural
      results obtained experimentally, indicating consistent values for the separation
      between the peptide planes as well as for nanosheet thickness. Energy analysis
      indicates that in general the stability of the nanosheets is dominated by
      electrostatic interactions and nanosheet-water environment interactions
      contribute considerably to stability. In general, the nanosheets were found to be
      very stable especially the EFL4FE system that presents a greater energy of
      interaction between the components of the system. PMF calculations indicate that
      the free energy required to remove a peptide from the nanosheet is greater than
      250 kJ mol-1 reaching the highest value of 310 kJ mol-1 for the extraction of the
      peptide in the EFL4FE nanosheet.

PMID- 29177295
TI  - Amino acid based gallium-68 chelators capable of radiolabeling at neutral pH.
AB  - Gallium-68 (68Ga) has been the subject of increasing interest for its potential
      in the production of radiotracers for diagnosis of diseases. In this work we
      report the complexation of 68Ga by the amino acid based tripodal chelate H3Dpaa,
      and two bifunctional derivatives, H3Dpaa.dab and H4Dpaa.ga, under a range of
      conditions with particular emphasis on the rapid complexation of 68Ga at pH 7.4.
      100 MUM H3Dpaa achieved a radiochemical yield of 95% at pH 7.4 in 5 minutes at 37
      degrees C. The bifunctional derivatives H4Dpaa.ga and H3Dpaa.dab achieved 94%
      and 84% radiochemical yields, respectively, under the same conditions. The
      resulting Ga(iii) complexes show thermodynamic stabilities of log KGaDpaa =
      18.53, log KGaDpaa.dab = 22.08, log KGaDpaa.ga = 18.36. Unfortunately, the
      resulting radiolabelled species do not present sufficient serum stability for in
      vivo application. Herein we show a flexible synthesis for bifunctional chelators
      based on amino acids that rapidly complex 68Ga under physiological conditions.

PMID- 29177296
TI  - Self-assembled polyoxometalate-dendrimer structures for selective photocatalysis.
AB  - We present a novel, self-assembled nanostructure with selective photocatalytic
      activity formed from anionic polyoxometalate clusters and cationic dendrimers by
      electrostatic self-assembly. The association of the components in aqueous
      solution is driven by ionic interaction and steric factors yielding stable
      aggregates of a defined size with a coil-like structure. The assemblies show high
      potential for the application in solar-energy conversion systems due to their
      enhanced and substrate specific photocatalytic activity.

PMID- 29177297
TI  - A flexible Sb2O3/carbon cloth composite as a free-standing high performance anode
      for sodium ion batteries.
AB  - A flexible Sb2O3/carbon cloth (CC) composite is synthesized using a simple
      solvothermal method. The Sb2O3/CC composite exhibits higher capacity and capacity
      retention of alloying and conversion reactions as an anode for sodium ion
      batteries, attributed to the good conductivity of CC and strong chemical bonds
      between Sb2O3 and CC.

PMID- 29177298
TI  - Photoswitchable nonlinear optical properties of metal complexes.
AB  - Incorporating photosensitive molecules into the organic/inorganic hybrid
      materials can contribute to forming photoresponsive systems. The second/third
      order nonlinear optical properties can be changed via external light stimulation
      at an appropriate wavelength. The photochromic metal complexes appear to be
      superior promising materials in the domain of photoswitchable nonlinear optics
      (NLO). Thus, the purpose of this review is to examine current progress of metal
      complexes in the field of photoswitchable NLO materials and provide perspectives
      for the future. The overview includes the second-order and third-order NLO
      photoswitches and NLO properties of metal complexes. Combined with the
      characteristics of pyrene and stilbazolium groups, we describe a new type of
      photoswitchable NLO materials. The rapidly increasing investigations in this
      domain suggest that NLO photoswitches of metal complexes would play a critical
      role for inspiring applications in the future.

PMID- 29177299
TI  - Axial stereocontrol in tropos dibenz[c,e]azepines: the individual and cooperative
      effects of alkyl substituents.
AB  - 6,7-Dihydro-5H-dibenz[c,e]azepines, a class of secondary amine incorporating a
      centre-axis chirality relay, can be prepared from N-(2-bromobenzyl)-N-(1
      arylalkyl)methanesulfonamides via Pd-catalysed intramolecular direct arylation,
      and methylated at C(7) via the 5,7-trans diastereoselective addition of
      methylmagnesium bromide to the derived N-benzylazepinium tetraphenylborate. Using
      these methods, the 4,5-dimethylated and 4,5,7-trimethylated homologues 13 and 14
      were obtained and shown by 1H NMR spectroscopy to be axially biased in opposite
      senses, as defined by the respective pseudoaxial or pseudoequatorial orientation
      of the 5-substituent in the preferred conformers, while retaining their tropos
      nature (the Arrhenius activation energy, EA, for the conformational exchange
      process in 14 was estimated to be 57 kJ mol-1 using 2D-EXSY NMR spectroscopy at
      233-248 K). These results serve to illustrate how substituent effects might be
      exploited in new designs of bridged biaryl ligand in which tropos dynamics
      operate in combination with a pre-existing axial stereochemical bias.

PMID- 29177300
TI  - Towards a dissociative SPC-like water model - probing the impact of
      intramolecular Coulombic contributions.
AB  - The dissociative water potential introduced by Garofalini et al. proved to be a
      simple and effective description to account for proton transfer in aqueous media,
      enabling for instance the execution of simulation studies at different pH values.
      In this model the charge of each particle is represented by a point-charge
      surrounded by a Gaussian charge-cloud of opposite sign, thus four Coulombic terms
      (point-charge-point-charge, point-charge-charge-cloud, charge-cloud-point-charge
      and charge-cloud-charge-cloud) are required per atom pair. In this work it is
      demonstrated that the Gaussian charge distributions can be removed from the model
      after a minor modification of the overall atomic point-charges. Despite this
      substantial modification of the model, structural properties obtained via pair-
      and angle distributions remain largely unaffected and the change in dynamical
      properties (vibrational frequencies, proton transfer properties) was found to be
      minor. As an additional improvement an adjustment of the bending mode vibration
      was carried out by carefully evaluating the parametrization of the three-body
      interaction potential, thereby retaining the good agreement of the transfer
      properties of the aqueous excess proton reported in an earlier study. The
      proposed simple point-charge (SPC) type parametrization of the Coulombic
      interactions not only leads to a notable decrease in computational demand but
      generalizes the dissociative model by improving its transferability to
      established third-party simulation software and enabling the application of
      different theoretical approaches such as Ewald summation techniques not
      considered in the original parametrization. The outlined optimization strategy
      demonstrates that despite the complex and challenging formulation of the force
      field, various dynamical properties can be selectively adjusted without
      influencing other critical parameters of the simulated systems.

PMID- 29177301
TI  - Photoresponsive ruthenium-containing polymers: potential polymeric metallodrugs
      for anticancer phototherapy.
AB  - This Frontier presents the recent development of photoresponsive Ru-containing
      polymers for cancer treatment. These novel Ru-containing polymers are prepared by
      introducing photoresponsive Ru complexes into polymers. Based on their chemical
      structures in aqueous solutions, these polymers can self-assemble into different
      nanostructures. The self-assembled nanostructures can circulate in the blood
      stream, accumulate at tumor tissue, and can be taken up by tumor cells. Red
      light, which can penetrate into tissue deeply, can induce the photodissociation
      of these polymers and sensitize singlet oxygen (1O2) generation. Both dissociated
      Ru complexes and generated 1O2 can inhibit the growth of tumor cells.
      Photoresponsive Ru-containing polymers provide a new platform for combined
      photodynamic therapy and photoactivated chemotherapy. The design strategies, self
      assembly, photoresponsiveness, and anticancer effects of these polymers are
      introduced. Some remaining challenges for Ru-containing polymers for phototherapy
      are discussed.

PMID- 29177302
TI  - A specific HeLa cell-labelled and lysosome-targeted upconversion fluorescent
      probe: PEG-modified Sr2YbF7:Tm3+ .
AB  - In this study, water-soluble PEG-modified Sr2YbF7:Tm3+ was prepared conveniently
      by a one-pot solvothermal method, where the molar ratio of Sr2+ to Yb3+ was
      controlled between 3 : 2 and 1 : 1. The optimum red-light emission at 677-699 nm
      was modulated via 0.7% Tm3+ doped under irradiation at 980 nm. Interestingly,
      biological experimental results showed that the PEG-modified Sr2YbF7:Tm3+ with
      low toxicity, excellent cell membrane permeability and high photostability can
      not only distinguish HeLa cells from mouse embryonic fibroblasts but also target
      the subcellular organelle lysosome in HeLa cells; therefore it can be anticipated
      that the as-prepared material would be a potential tool for cancer diagnosis.

PMID- 29177303
TI  - Reducing the photocatalysis induced by hot electrons of plasmonic nanoparticles
      due to tradeoff of photothermal heating.
AB  - Silver nanotetrahedron (AgNT) two-dimensional arrays on a glass substrate
      generate nonthermal hot electrons, which induced photocatalytic oxidation of 4,4
      dimercaptoazobenzene (DMAB) adsorbed onto its surface. The rate of the
      photocatalytic oxidation of DMAB is found to decrease upon increasing the
      intensity of the excitation light, unlike traditional photocatalysis reactions.
      The amount of 4-nitrothiophenol (4-NTP) resulting from the photocatalytic
      oxidation of DMAB is lower than expected, suggesting the partial desorption of
      DMAB or 4-NTP molecules from the surface of the AgNTs. However, the hot electrons
      remaining from the photocatalysis reaction thermalize and transfer their energy
      to the nanoparticle lattices, generating heat. The photothermal heat is
      sufficient to dissociate the Ag-S bond causing desorption of both DMAB and 4-NTP.

PMID- 29177304
TI  - Dehalogenation of vicinal dihalo compounds by 1,1'-bis(trimethylsilyl)-1H,1'H
      4,4'-bipyridinylidene for giving alkenes and alkynes in a salt-free manner.
AB  - We report a transition metal-free dehalogenation of vicinal dihalo compounds by
      1,1'-bis(trimethylsilyl)-1H,1'H-4,4'-bipyridinylidene (1) under mild conditions,
      in which trimethylsilyl halide and 4,4'-bipyridine were generated as byproducts.
      The synthetic protocol for this dehalogenation reaction was effective for a wide
      scope of dibromo compounds as substrates while keeping the various functional
      groups intact. Furthermore, the reduction of vicinal dichloro alkanes and vicinal
      dibromo alkenes also proceeded in a salt-free manner to afford the corresponding
      alkenes and alkynes.

PMID- 29177305
TI  - A novel tin hybrid nano-composite with double nets of carbon matrixes as a stable
      anode in lithium ion batteries.
AB  - A novel battery hybrid composite anode consisting of tin nanoparticles
      encapsulated by double nets of carbon matrixes is presented. The improved
      electron transfer and volume change accommodation are confirmed via density
      functional theory modeling and in situ transmission electron microscopy
      observations, respectively.

PMID- 29177306
TI  - Remediation mechanisms for Cd-contaminated soil using natural sepiolite at the
      field scale.
AB  - Remediation of heavy metal polluted agricultural soil is essential for human
      health and ecological safety and remediation mechanisms at the microscopic level
      are vital for their large-scale utilization. In this study, natural sepiolite was
      employed as an immobilization agent for in situ field-scale remediation of Cd
      contaminated paddy soil and the remediation mechanisms were investigated in terms
      of soil chemistry and plant physiology. Natural sepiolite had a significant
      immobilization effect for bioavailable Cd contents in paddy soil, and
      consequently could lower the Cd concentrations of brown rice, husk, straw, and
      roots of rice plants by 54.7-73.7%, 44.0-62.5%, 26.5-67.2%, and 36.7-46.7%,
      respectively. Regarding soil chemistry, natural sepiolite increased the soil pH
      values and shifted the zeta potentials of soil particles to be more negative,
      enhancing the fixation or sorption of Cd on soil particles, and resulted in the
      reduction of HCl and DTPA extractable Cd concentrations in paddy soil. Natural
      sepiolite neither enhanced nor inhibited iron plaques on the rice root surface,
      but did change the chemical environments of Fe and S in rice root. Natural
      sepiolite improved the activities of antioxidant enzymes and enhanced the total
      antioxidant capacity to alleviate the stress of Cd. It also promotes the
      synthesis of GSH and NPT to complete the detoxification. In general, the
      remediation mechanisms of natural sepiolite for the Cd pollutant in paddy soil
      could be summarized as the collective effects of soil chemistry and plant
      physiology.

PMID- 29177307
TI  - Physicochemical stability, antioxidant properties and bioaccessibility of beta
      carotene in orange oil-in-water beverage emulsions: influence of carrier oil
      types.
AB  - This study investigated the effect of carrier oils (short-chain triglycerides
      (SCT) vs. long-chain triglycerides (LCT)) on the physical stability, chemical
      degradation, antioxidant properties and bioaccessibility of beta-carotene-loaded
      orange oil-in-water beverage emulsions. Beverages formulated with 50% LCT (corn
      oil) were physically more stable compared to the ones with 50% SCT (tributyrin)
      as indicated by the Turbiscan 32 Stability Indices during chilled storage for 28
      days. No chemical degradation of beta-carotene was observed during storage
      regardless of the carrier oil composition. The formation of primary (conjugated
      dienes) or secondary (thiobarbituric acid reactive substances) oxidation products
      at the end of the storage period was insignificant. The bioaccessibility of beta
      carotene was significantly affected (P < 0.05) by the type of carrier oil and
      decreased in the following order: 50% LCT + 50% orange oil > 50% SCT + 50% orange
      oil > 100% orange oil. The high bioaccessibility of beta-carotene (30.06%) in the
      beverages formulated with LCTs was attributed to the enhanced solubilisation
      capacity of the lipophilic carotenoid in mixed micelles after the in vitro
      digestion protocol.

PMID- 29177308
TI  - Discovery of IDO1 and DNA dual targeting antitumor agents.
AB  - The development of small molecules for cancer immunotherapy is highly challenging
      and indoleamine 2,3-dioxygenase 1 (IDO1) represents a promising target. Inspired
      by the synergistic effects between IDO1 inhibitors and traditional antitumor
      chemotherapeutics, the first orally active dual IDO1 and DNA targeting agents
      were designed by the pharmacophore fusion strategy. The bifunctional hybrids
      exhibited enhanced IDO1 enzyme inhibitory activity and in vitro cytotoxicity as
      compared to IDO1 inhibitor 1-methyl-tryptophan and DNA alkylating agent
      melphalan. In a murine LLC tumor model, the dual targeting agents demonstrated
      excellent antitumor efficacy, highlighting the advantages of this novel design
      strategy to improve the efficacy of small molecule cancer immunotherapy.

PMID- 29177309
TI  - Horizontal drying fronts in films of colloidal dispersions: influence of
      hydrostatic pressure and collective diffusion.
AB  - The origin and time evolution of heterogeneities in drying colloidal films is
      still a matter of debate. In this work, we studied the behaviour of horizontal
      drying fronts in a 1D configuration. The effects of hydrostatic pressure and
      collective diffusion of charged particles, neglected so far, were introduced. We
      made use of the new simulation tool based on cellular automata we recently
      presented (Langmuir 2015 & 2017). To check the simulation results, measurements
      of film profiles in the wet state and drying front velocities were performed with
      silica colloids. It was shown that taking hydrostatic pressure into account much
      improves agreement between theory and experiment. On the other hand, the
      simulation showed that collective diffusion slows down the drying fronts, even
      more when the Debye length is increased. This latter effect remains to be checked
      experimentally. This work opens the way to further improvements of theory and
      simulation, notably 2D and 3D simulations.

PMID- 29177310
TI  - Non-Gaussian elasticity and charge density-dependent swelling of strong
      polyelectrolyte poly(N-isopropylacrylamide-co-sodium acrylate) hydrogels.
AB  - The mechanical properties and charge density-dependent swelling of strong
      polyelectrolyte poly(N-isopropylacrylamide-co-sodium acrylate) P(NIPA-co-NaA)
      hydrogels prepared at a fixed total monomer concentration and crosslinker ratio,
      but at various charge densities, i.e. NaA content in the feed between 0 and 90
      mol%, were investigated. The elasticity results were discussed to explain the
      relationship between the elastic free energy DeltaGel and the swelling ratio
      alpha as well as to fit the existing theories to the swelling data. The
      implications of the obtained results for the deviation from the Gaussian chain
      statistics were considered. Given the swollen elastic modulus and the dependence
      of charge density on the equilibrium gel volume, it would seem that the latter
      factor is an important determinant of non-Gaussian elasticity of polyelectrolyte
      P(NIPA-co-NaA) hydrogels containing strongly dissociated groups. The dependence
      of the reduced modulus on the equilibrium gel volume was found to be Gr ~ (Veq)
      0.47 at low swelling degree and Gr ~ (Veq)0.64 at high swelling degree and the
      deviation was interpreted as the non-Gaussian elasticity of equilibrium swollen
      P(NIPA-co-NaA) hydrogels. The detailed theoretical treatments of non-Gaussian
      elasticity of P(NIPA-co-NaA) hydrogels and, in particular, the influence of the
      charge density on the elasticity showed that the knowledge of several swollen
      state parameters and the effective charge density distribution of hydrogels were
      strongly required to explain the variation of the elastic properties depending on
      the ionic group content. Within this framework, the dominant mechanism
      responsible for the deviation from Gaussian elasticity and the finite chain
      extensibility of ionic P(NIPA-co-NaA) hydrogels was described and the results
      were used to explain the dependence of the elastic modulus on the equilibrium gel
      volume.

PMID- 29177311
TI  - Insight into the effect mechanism of urea-induced protein denaturation by
      dielectric spectroscopy.
AB  - Dielectric relaxation spectroscopy was applied to study how urea affects the
      phase transition of a thermosensitive polymer, poly(N-isopropylacrylamide)
      (PNIPAM), which has been widely used as a protein model. It was found that there
      is a pronounced relaxation near 10 GHz for the ternary system of PNIPAM in urea
      aqueous solution. The temperature dependence of dielectric parameters indicates
      that urea can reduce the lower critical solution temperature (LCST) of PNIPAM,
      i.e., stabilize the globule state of PNIPAM and collapse the PNIPAM chains. Based
      on our results, the interaction mechanism of urea on the conformational
      transition of PNIPAM was presented: urea replaces water molecules directly
      bonding with PNIPAM and acts as the bridging agent for the adjacent side chains
      of PNIPAM. Accordingly, the mechanism with which urea denatures protein was
      deduced. In addition, it is worth mentioning that, from the temperature
      dependence of the dielectric parameters obtained in the presence of urea, an
      interesting phenomenon was found in which the effect of urea on PNIPAM seems to
      take 2 M as a unit. This result may be the reason why urea and TMAO exit marine
      fishes at a specific ratio of 2 : 1.

PMID- 29177312
TI  - Ru decorated with NiCoP: an efficient and durable hydrogen evolution reaction
      electrocatalyst in both acidic and alkaline conditions.
AB  - The construction of a high efficiency and stable catalyst for use in
      electrochemical hydrogen generation has great significance for renewable energy
      technologies. Herein, we show for the first time that Ru decorated with NiCoP is
      an excellent hydrogen evolving catalyst in both acidic and alkaline conditions,
      close in performance to that of Pt/C.

PMID- 29177314
TI  - Distal radical migration strategy: an emerging synthetic means.
AB  - The remote radical migration strategy has gained considerable momentum. During
      the past three years, we have witnessed the rapid development of sustainable and
      practical C-C and C-H bond functionalization by means of long-distance 1,n
      radical migration (n = 4, 5, 6) events. Its advent brings our chemical community
      a new platform to deal with the challenging migration transformations and thus
      complements the existing ionic-type migration protocols. In this review, the
      recent achievements in distal radical migration triggered C-C and C-H bond
      functionalization are summarized.

PMID- 29177315
TI  - Photoassisted bottom-up construction of plasmonic nanocity.
AB  - Herein, photoassisted self-construction of nanocity as a novel plasmonic
      metasurface was achieved. It is an ensemble of nanobuildings, and the height of
      each nanobuilding is greater than its depth. Plasmonic nanocity exhibits a
      vertical resonance mode in addition to distal longitudinal and proximal
      longitudinal resonance modes, such that it can be applied to chromatic angular
      polarizers, sophisticated image recording, and high density data storage. Further
      growth of nanobuildings to bulky and tall nanocuboids leads to asymmetric and
      dichroic scattering, which can be applied in security printing.

PMID- 29177316
TI  - Rat ceruloplasmin: a new labile copper binding site and zinc/copper mosaic.
AB  - Ceruloplasmin (Cp) is a copper-containing multifunctional oxidase of plasma, an
      antioxidant, an acute-phase protein and a free radical scavenger. The structural
      organization of Cp causes its sensitivity to proteolysis and ROS (reactive oxygen
      species), which can alter some of the important Cp functions. Elucidation of the
      orthorhombic crystal structure of rat Cp at 2.3 A resolution revealed the basis
      for stronger resistance of rat Cp to proteolysis and a new labile copper binding
      site. The presence of this site appears as a very rare and distinctive feature of
      rat Cp as was shown by sequence alignment of ceruloplasmin, hephaestin and
      zyklopen in the Deuterostomia taxonomic group. The trigonal crystal form of rat
      Cp at 3.2 A demonstrates unexpected partial substitution of copper by zinc.

PMID- 29177317
TI  - Unfolding of a comb-like polymer in a poor solvent: translation of macromolecular
      architecture in the force-deformation spectra.
AB  - A numerical self-consistent field modeling approach was employed to study the
      mechanical unfolding of a globule made by comb-like polymers in a poor solvent
      with the aim of unraveling how the macromolecular architecture affects the shape
      of the single-molecule force-deformation curves. We demonstrate that the
      dependence of the restoring force on the imposed extension of the main chain of
      the comb-like polymer exhibits a characteristic oscillatory shape in the
      intermediate deformation range. Theoretical arguments are developed that enable
      us to relate the shape of the patterns on the force-deformation curves to the
      molecular architecture (grafting density and length of the side chains) and
      interaction parameters. Thus, the results of our study suggest a new approach for
      the determination of macromolecular topology from single-molecule mechanical
      unfolding experiments.

PMID- 29177318
TI  - Dielectric transitions and relaxations in Ca(ii)Co(iii)-based cyanometallate
      frameworks with a rare (6,6)-connected nia topology.
AB  - A series of cyanometallate frameworks A[CaCo(CN)6] (A = protonated guanidine,
      urea or thiourea guest) exhibit a rare (6,6)-connected nia topology with the
      Schlafli symbol of (412.63)(49.66) and thermally driven dielectric transitions
      and relaxations without evident structural phase transitions.

PMID- 29177319
TI  - Specifically targeting mixed-type dimeric G-quadruplexes using berberine dimers.
AB  - Three polyether-tethered berberine dimers (1a-c) were studied for their binding
      affinity, selectivity and thermal stabilization towards human telomeric dimeric
      quadruplex DNA (G2T1). Compound 1a with the shortest polyether linker showed the
      highest affinity (Ka > 108 M-1) and 76-508-fold higher selectivity for mixed-type
      G2T1 over antiparallel G2T1 and three monomeric G-quadruplexes, which are human
      telomeric monomeric quadruplex G1, c-kit 1 and c-kit 2. Compound 1a induced the
      formation of quadruplex structures and showed higher thermal stabilization for
      mixed-type G2T1 than for anti-parallel G2T1, G1 and ds DNA. Spectroscopic studies
      suggest that compound 1a could bind to mixed-type G2T1 via end-stacking and
      external binding modes. These results suggest that the polyether linkers in these
      compounds play an important role in regulating the binding affinity and
      selectivity towards mixed-type G2T1 and that compound 1a could target mixed-type
      G2T1 at other genome regions with antiparallel G2T1 and monomeric G-quadruplexes.
      These results may provide useful guidance for the rational design of selective
      multimeric G-quadruplex binders and potential anticancer agents.

PMID- 29177324
TI  - Tuning the inter-molecular charge transfer, second-order nonlinear optical and
      absorption spectra properties of a pi-dimer under an external electric field.
AB  - In this work, we applied an external electric field (F) to a biphenalenyl
      derivative (BN-PLY2) in the direction of the negative z-axis (F-z) and the
      positive z-axis (F+z), respectively. The influence of the two directions of F on
      the molecular structures and electronic properties is investigated, which gives
      interesting results. Density functional theory (DFT) calculations show that the
      application of F-z (F-z = 0 to -190 * 10-4) is an advantage toward improving pi
      dimer stability, which is attributed to an increase in bonding and attractive
      electrostatic interactions. Interestingly, a large amount of negative charge is
      induced by applying F-z to the upper layer, resulting in an increase in the
      electron density in the upper layer, which is the main factor for the formation
      of a symmetric highest occupied molecular orbital (HOMO) at F-z = -180 * 10-4 au
      (-9.26 * 109 V m-1). Moreover, when F+z is applied, the HOMO and HOMO-1 undergo
      orbital interchange in the pi-dimer at F+z = 100/110 * 10-4 au. Significantly,
      the effect of the external electric field effectively regulates the first
      hyperpolarizabilities (betatot). When the F+z ranges from 0 to 140 * 10-4 au, the
      betatot values slightly decrease to 0 au. Note that, upon increasing F+z, the
      betatot values sharply increase to 6.67 * 103 au (F+z = 190 * 10-4 au).
      Furthermore, the evolutions of the absorption spectra under F might well explain
      the trend of betatot values. When the F+z ranges from 0 to 140 * 10-4 au, the
      broad absorption spikes with a low-energy are significantly blue-shifted, while
      only absorption spikes with a high-energy are significantly red-shifted (F+z =
      140 to 190 * 10-4 au). The present work not only provides a deeper understanding
      of the relationships between the molecular structure and the electronic
      properties of a pi-dimer system, but can also be developed for designing highly
      efficient nonlinear optical materials through the influence of an external
      electric field.

PMID- 29177325
TI  - A domain-based DNA circuit for smart single-nucleotide variant identification.
AB  - According to the differential information of four homologous oligonucleotides,
      two domain-based encoders have been constructed with the molecular information as
      the input. Based on the one-to-one correspondence between the input and output,
      SNVs can be identified and their sites can be located at the domain level.

PMID- 29177326
TI  - Surface-enhanced Raman scattering II: concluding remarks.
AB  - Surface-enhanced Raman scattering (SERS) enables the detection of a large number
      of different adsorbates at extraordinarily low levels. This plasmonics-based
      technology has undergone a number of remarkable advances since its discovery over
      40 years ago, and has emerged from being an investigative tool confined largely
      to the research laboratory into a much more usable tool across a broad range of
      investigative studies, both within the laboratory and beyond. The purpose of this
      Concluding remarks manuscript is to capture, at least in part, the developments
      in this area since the first Faraday discussion of SERS over a decade ago. It
      begins with a brief contextual overview and then moves into describing a few of
      the many highlights from the meeting. Along the way, we have added a few comments
      and perspectives as a means to more fully stage where the different areas of
      research with SERS stand today. An addendum is included that collects a few of
      the recent perspectives on the original work and activities in this area.

PMID- 29177327
TI  - Effects of the SrTiO3 support on visible-light water oxidation with Co3O4
      nanoparticles.
AB  - The photocatalytic activity of SrTiO3 modified with Co3O4 nanoparticles for water
      oxidation under visible light (lambda > 480 nm) was investigated with respect to
      the physicochemical properties of the SrTiO3 support. SrTiO3 was synthesized by a
      polymerized complex method or a hydrothermal method, followed by calcination in
      air at different temperatures in order to obtain SrTiO3 particles having
      different sizes. Co3O4 nanoparticles, which provide both visible light absorption
      and water oxidation centers, were loaded on the as-prepared SrTiO3 by an
      impregnation method using Co(NO3)2 as the precursor, followed by heating at 423 K
      in air. Decreasing the SrTiO3 particle size (that is, improving the
      crystallinity) enhanced the photocatalytic activity by promoting the formation of
      Co3O4 nanoparticles that provided optimal light absorption and catalytic sites.
      However, Co3O4 aggregation occurred on overly large SrTiO3 particles, leading to
      a decrease in activity. This study demonstrates the possibility of tuning the
      photocatalytic activity of a Co3O4-loaded wide-gap semiconductor for visible
      light water oxidation through the appropriate selection of the support material.

PMID- 29177328
TI  - Synthesis of cyclopent-2-enones from furans using a nebulizer-based continuous
      flow photoreactor.
AB  - A series of hydroxycyclopent-2-enones and methoxycyclopent-2-enones have been
      synthesized in a single operation from simple furan substrates using an
      innovative continuous flow nebulizer system (NebPhotOX). Photooxygenation of the
      furan substrates takes place in an aerosol within the NebPhotOX system.

PMID- 29177329
TI  - Triphenylamine flanked furan-diketopyrrolopyrrole for multi-imaging guided
      photothermal/photodynamic cancer therapy.
AB  - The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) is
      highly desired to improve the cancer phototherapeutic effect. However, most
      reported multicomponent therapeutic agents need complex preparation processes and
      must be excited by using multiple light sources. Herein, triphenylamine flanked
      furan-diketopyrrolopyrrole (FDPP-TPA) with a donor-acceptor-donor structure has
      been synthesized and used as a sole-component agent for fluorescence,
      photoacoustic and photothermal imaging guided photodynamic and photothermal
      synergistic therapy. FDPP-TPA nanoparticles (NPs) obtained by re-precipitation
      exhibit a high molar extinction coefficient (epsilon = 2.13 (+/-0.2) * 104 M-1 cm
      1), excellent photothermal conversion efficiency (eta = 47%) and favorable
      singlet oxygen quantum yield (PhiDelta(X) = 40%). In vitro, the half-maximal
      inhibitory concentration (IC50) is 13 MUg mL-1 determined by cytotoxicity assay.
      And the apoptosis rate is 67.3% according to flow cytometry analysis. In vivo,
      the tumor can be completely ablated without recurrence, which suggests that FDPP
      TPA NPs can generate considerable poisonous singlet oxygen and hyperthermia for
      tumor treatment.

PMID- 29177330
TI  - Controlling the H to T' structural phase transition via chalcogen substitution in
      MoTe2 monolayers.
AB  - New materials exhibiting reversible structural transitions are desired for a
      variety of applications, yet they are difficult to identify and stabilize.
      Monolayer MoTe2 has emerged as a good candidate as it displays a small energy
      difference between a semiconducting H and semimetallic T' phase; however,
      switching between the two phases is difficult. Here, we propose using chalcogen
      alloying to overcome this challenge. Using first principles density functional
      theory calculations, we investigate 7 MoTe2-xXx alloys (X = N, P, Sb, F, Br, I,
      and Se) at three concentrations. We find that the energy difference between the H
      and T' phases is dependent on the chemistry, size, and concentration of the
      dopant atom, providing significant control over the stability of the two phases.
      From the thermodynamic stability of these compounds, we show that several can be
      stabilized under the appropriate experimental conditions. We also find that P
      alloying enhances the chemical reactivity of the basal plane towards a variety of
      adsorbates. Finally, we show that mechanical strain makes it is easier to
      stabilize and dynamically switch between the two states than in unalloyed MoTe2.
      Our results suggest that Te substitution in monolayer MoTe2 is a way to induce
      and control a reversible structural phase transition in this two-dimensional
      material system.

PMID- 29177331
TI  - Probing molecular forces in multi-component physiological membranes.
AB  - Biological membranes are remarkably heterogeneous, composed of diverse lipid
      mixtures with distinct chemical structure and composition. By combining molecular
      dynamics simulations and the newly developed Lipid-Force Distribution Analysis (L
      FDA), we explore force transmission in complex multi-component membrane models
      mimicking eukaryotic organelles. We found that the chemical-moiety based
      segmentation at membrane interfaces revealed a distinctive distribution of bonded
      and non-bonded forces in diverse membrane environment. Our molecular stress
      analysis could have far-reaching implications in describing the relationship
      between membrane mechanical properties and functional states of chemically
      distinct lipids.

PMID- 29177332
TI  - NiCo2S4 nanosheet-decorated 3D, porous Ni film@Ni wire electrode materials for
      all solid-state asymmetric supercapacitor applications.
AB  - Wire type supercapacitors with high energy and power densities have generated
      considerable interest in wearable applications. Herein, we report a novel NiCo2S4
      decorated 3D, porous Ni film@Ni wire electrode for high performance
      supercapacitor application. In this work, a facile method is introduced to
      fabricate a 3D, porous Ni film deposited on a Ni wire as a flexible electrode,
      followed by decoration with NiCo2S4 as an electroactive material. The fabricated
      NiCo2S4-decorated 3D, porous Ni film@Ni wire electrode displays a superior
      performance with an areal and volumetric capacitance of 1.228 F cm-2 and 199.74 F
      cm-3, respectively, at a current density of 0.2 mA cm-1 with a maximum volumetric
      energy and power density (EV: 6.935 mW h cm-3; PV: 1.019 W cm-3). Finally, the
      solid state asymmetric wire type supercapacitor is fabricated using the
      fabricated NiCo2S4-decorated 3D, porous Ni film@Ni wire as a positive electrode
      and N-doped reduced graphene oxide (N-rGO) as a negative electrode and this
      exhibits good areal and volumetric capacitances of CA: 0.12 F cm-2 and CV: 19.57
      F cm-2 with a higher rate capability (92%). This asymmetric wire type
      supercapacitor demonstrates a low leakage current and self-discharge with a
      maximum volumetric energy (EV: 5.33 mW h cm-3) and power (PV: 855.69 mW cm-3)
      density.

PMID- 29177333
TI  - Tetraazapentacene constructs: controlling bulk-morphology through molecular
      dimensionality.
AB  - Multi-core TIPSTAP-constructs of different dimensionality were created via
      "geometrization" of the monomeric, highly crystalline parent using alkyne
      linkers. Morphological diversity is produced, while the material acceptor
      strength remains untouched. We establish structure-function relationships as the
      bulk morphology is predicted from the molecular geometry.

PMID- 29177334
TI  - Large-area potassium-doped highly conductive graphene films for electromagnetic
      interference shielding.
AB  - As promising carbonaceous films, graphene films (GF) have exhibited many
      remarkable mechanical and electrical/thermal properties of great potential for
      wide functional applications. However, the electrical conductivity of GF still
      needs to be improved and the limitation lies in the low carrier density of pure
      graphene. Here, we presented a post-doping method for large-area potassium doped
      graphene films (GF-K) and promoted the electrical conductivity of GF approaching
      benchmark metals. The macroscopic-assembled GF-K shows a similar color to
      graphite intercalation compounds. The potassium doping increased the carrier
      density of the GF without undermining the electronic quality of the graphene
      unit. The doping concentration was optimized to prepare stage-2 GF-K (C24K) with
      the highest electrical conductivity (1.49 * 107 S m-1), holding merits of low
      density (1.63 g cm-3), and high flexibility. Doped GF with better specific
      electrical conductivity than copper showed outstanding electromagnetic
      interference shielding performance. Shielding effectiveness (SE) increased from
      70-85 dB for graphene film (GF) to over 130 dB for GF-K only at 31 MUm thickness,
      which is among the best SEs in previous reports. The combination of high specific
      conductivity, mechanical flexibility, high EMI SE, light weight, and facile
      productivity enables GF-K to be promising in many high-end EMI applications such
      as aerospace and wearable devices.

PMID- 29177335
TI  - Molecular actions of hypocholesterolaemic compounds from edible mushrooms.
AB  - Cholesterol levels are strictly regulated to maintain its homeostasis; therefore,
      if it is not absorbed with the diet, the cholesterol biosynthetic pathway is
      enhanced and vice versa. Nowadays, the commonly prescribed therapeutic treatments
      for hypocholesterolemic patients are targeted toward the reduction of both
      cholesterol intestinal absorption and/or its endogenous biosynthesis. But, when
      hypercholesterolemia is still moderate the consumption of food products with
      cholesterol-lowering capacities is more desirable than using drugs. Marketed
      foods supplemented with hypocholesterolemic compounds are only inhibiting
      mechanisms for cholesterol absorption (i.e. phytosterols and cereal beta
      glucans). However, certain fungal extracts obtained from edible mushrooms might
      be able to modulate cholesterol levels by both strategies, pharmaceutical drugs
      and functional foods. In vitro and in vivo studies indicated that fungal sterols
      down-regulated genes involved in cholesterol homeostasis (such as Srebf2 and
      Nr1h4 (FXR)) and other specific mushroom extracts (beta-glucans and other water
      soluble compounds) also stimulated transcriptional profiles similar to
      simvastatin or ezetimibe (two hypocholesterolemic drugs). These and other
      observations suggested that the hypocholesterolemic effect of mushroom extracts
      could be due to transcriptional and post-transcriptional modulations besides
      other indirect effects.

PMID- 29177336
TI  - New insight into an efficient visible light-driven photocatalytic organic
      transformation over CdS/TiO2 photocatalysts.
AB  - Selective transformation of organics by visible-light-driven photocatalysis has
      been considered as a green and efficient strategy for the synthesis of fine
      chemicals. Herein, we fabricated mesoporous structured TiO2 with CdS
      nanoparticles successfully by a photodeposition method. The photocatalytic
      selective oxidation of benzyl alcohols and reduction of 4-nitroaniline were
      demonstrated over the as-prepared samples under visible-light irradiation. The
      CdS-decorated TiO2 with the photodeposition time of 90 min exhibited highest
      activity, which was higher than that of the commercial CdS, bare TiO2, CdS/P25,
      and CdS/SiO2. Further experimental results indicated that the higher performance
      was attributed to the moderate deposition of CdS forming a closely connected
      heterojunction with TiO2, which promoted the separation of photogenerated
      electrons and holes. Based on the results of active species detection, possible
      mechanisms for photocatalytic selective oxidation of benzyl alcohol and reduction
      of 4-nitroaniline were proposed. Our study may provide guidance for selective
      transformation of organics via construction of heterojunction photocatalysts.

PMID- 29177337
TI  - Lower lattice thermal conductivity in SbAs than As or Sb monolayers: a first
      principles study.
AB  - Phonon transport in group-VA element (As, Sb and Bi) monolayer semiconductors has
      been widely investigated in theory, and, of them, monolayer Sb (antimonene) has
      recently been synthesized. In this work, phonon transport in monolayer SbAs is
      investigated with a combination of first-principles calculations and the
      linearized phonon Boltzmann equation. It is found that the lattice thermal
      conductivity of monolayer SbAs is lower than those of both monolayer As and Sb,
      and the corresponding sheet thermal conductance is 28.8 W K-1 at room
      temperature. To understand the lower lattice thermal conductivity in monolayer
      SbAs than those in monolayer As and Sb, the group velocities and phonon lifetimes
      of monolayer As, SbAs and Sb are calculated. The calculated results show that the
      group velocities of monolayer SbAs are between those of monolayer As and Sb, but
      that the phonon lifetimes of SbAs are smaller than those of both monolayer As and
      Sb. Hence, the low lattice thermal conductivity in monolayer SbAs is attributed
      to very small phonon lifetimes. Unexpectedly, the ZA branch has very little
      contribution to the total thermal conductivity, only 2.4%, which is obviously
      different from those of monolayer As and Sb with very large contributions. This
      can be explained by very small phonon lifetimes for the ZA branch of monolayer
      SbAs. The lower lattice thermal conductivity of monolayer SbAs compared to that
      of monolayer As or Sb can be understood by the alloying of As (Sb) with Sb (As),
      which should introduce phonon point defect scattering. We also consider the
      isotope and size effects on the lattice thermal conductivity. It is found that
      isotope scattering produces a neglectful effect, and the lattice thermal
      conductivity with a characteristic length smaller than 30 nm can reach a decrease
      of about 47%. These results may offer perspectives on tuning the lattice thermal
      conductivity by the mixture of multiple elements for applications of thermal
      management and thermoelectricity, and motivate further experimental efforts to
      synthesize monolayer SbAs.

PMID- 29177338
TI  - Mapping of exciton-exciton annihilation in MEH-PPV by time-resolved spectroscopy:
      experiment and microscopic theory.
AB  - Transient absorption traces taken on samples of the polymer MEH-PPV are measured
      as a function of the laser intensity. In increasing the laser power, different
      decay dynamics of the signal are obtained. This suggests that effective exciton
      exciton annihilation takes place. The signals are interpreted using a microscopic
      quantum mechanical model. The analysis points at an ultrafast excitonic decay via
      interchain and intrachain annihilation, where the latter process is roughly
      thirty times slower. Afterwards, diffusion-induced annihilation and relaxation
      become effective and thus determine the long-time behavior of the excited-state
      decay.

PMID- 29177339
TI  - Adaptable piezoelectric hemispherical composite strips using a scalable groove
      technique for a self-powered muscle monitoring system.
AB  - Contrary to traditional planar flexible piezoelectric nanogenerators (PNGs),
      highly adaptable hemispherical shape-flexible piezoelectric composite strip (HS
      FPCS) based PNGs are required to harness/measure non-linear surface motions.
      Therefore, a feasible, cost-effective and less-time consuming groove technique
      was developed to fabricate adaptable HS-FPCSs with multiple lengths. A single HS
      CSPNG generates 130 V/0.8 MUA and can also work as a self-powered muscle
      monitoring system (SP-MMS) to measure maximum human body part movements, i.e.,
      spinal cord, throat, jaw, elbow, knee, foot stress, palm hand/finger force and
      inhale/exhale breath conditions at a time or at variable time intervals.

PMID- 29177340
TI  - Real-time observation of solubilization-induced morphological change in
      surfactant aggregates adsorbed on a solid surface.
AB  - A solubilization-induced morphological change in surfactant surface aggregates
      was imaged in real-time, using high-speed atomic force microscopy. We revealed
      that the morphological change occurred within a few hundred seconds and was
      irreversible in the addition/removal process of organic solutes.

PMID- 29177341
TI  - Chemical reaction dynamics.

PMID- 29177342
TI  - Rhodium-catalyzed carbonylative synthesis of silyl-substituted indenones.
AB  - A novel and efficient rhodium-catalyzed procedure for the preparation of silyl
      substituted indenones has been developed. Using silanes and internal alkynes as
      the substrates, in the presence of CO, good to excellent yields of the desired
      indenones were isolated. A wide range of functional groups, encompassing esters,
      amines, nitriles and halides, is compatible in this system.

PMID- 29177343
TI  - Intrinsic anionic rearrangement by extrinsic control: transition of RS and CRS in
      thermally elevated TiN/HfO2/Pt RRAM.
AB  - The sneak path problem is one of the major hindrances to the application of high
      density crossbar resistive random access memory; however, complementary resistive
      switching (CRS) is an effective solution to this problem. The co-existence of
      resistive switching (RS) and CRS is possible within the same device. Therefore, a
      precise control is highly required for the successful utilization of different
      modes. In this study, we have demonstrated an effective way to control both
      switching modes in a simple HfO2-based crossbar device. The interchange between
      RS and CRS modes is possible, based on the intrinsic anionic rearrangement by
      controlling the extrinsic stimulation, either in the form of voltage or in the
      form of current. In particular, a highly nonlinear CRS mode is reported, in which
      the nonlinearity is almost 100 times greater than in the RS mode, which is
      achieved at a high temperature of 150  degrees C. The procedure reported in this
      study may be useful for the other resistive memory systems.

PMID- 29177344
TI  - Robust oil-core nanocapsules with hyaluronate-based shells as promising
      nanovehicles for lipophilic compounds.
AB  - The design of nanodelivery systems has been recently considered as a solution to
      the major challenge in pharmaceutical research - poor bioavailability of
      lipophilic drugs. Nanocapsules with liquid oil cores and shells based on
      amphiphilic polysaccharides were developed here as robust carriers of hydrophobic
      active compounds. A series of modified charged hyaluronates were synthesized and
      used as stabilizing shells ensuring also the biocompatibility of the nanocapsules
      that is crucial for applications related to the delivery of lipophilic drugs in
      vivo. Importantly, the oil nanodroplets were found to be stably suspended in
      water for at least 15 months without addition of low molar mass surfactants.
      Moreover, their size and stability may be tuned by varying the relative content
      of hydrophobic and hydrophilic groups in the hyaluronate derivatives as was
      confirmed by dynamic light scattering and nanoparticle tracking analysis as well
      as electron microscopy. In vivo studies demonstrated that hyaluronate-based
      nanocapsules accumulated preferentially in the liver as well as in the lungs.
      Moreover, their accumulation was dramatically potentiated in endotoxemic mice. In
      vitro studies showed that the nanocapsules were taken up by liver sinusoidal
      endothelial cells and by mouse lung vascular endothelial cells. Importantly, the
      capsules were found to be nontoxic in an acute oral toxicity experiment even at a
      dose of 2000 mg per kg b.w. Biocompatible hyaluronate-based nanocapsules with
      liquid cores described herein represent a promising and tunable nanodelivery
      system for lipophilic active compounds via both oral and intravenous
      administration.

PMID- 29177345
TI  - Bioavailability of hydroxycinnamates in an instant green/roasted coffee blend in
      humans. Identification of novel colonic metabolites.
AB  - Roasting greatly reduces the phenolic content in green coffee beans. Considering
      the beneficial effects of coffee polyphenols, blends containing green coffee
      beans are being consumed as a healthier alternative to roasted coffee. This study
      was aimed at assessing the absorption and metabolism of hydroxycinnamates in an
      instant green/roasted (35/65) coffee blend in healthy humans. Twelve fasting men
      and women consumed a cup of coffee containing 269.5 mg (760.6 MUmol) of
      chlorogenic acids. Blood and urine samples were taken before and after coffee
      consumption at different times and analyzed by LC-MS-QToF. Up to 25 and 42
      metabolites were identified in plasma and urine, respectively, mainly in the form
      of sulfate and methyl derivatives, and to a lower extent as glucuronides. Un
      metabolized hydroxycinnamate esters (caffeoyl-, feruloyl-, and coumaroylquinic
      acids), hydroxycinnamic acids (caffeic, ferulic and coumaric acids) and their
      phase II metabolites, in addition to phase II derivatives of lactones,
      represented a minor group of metabolites (16.3% of the metabolites excreted in
      urine) with kinetics compatible with small intestine absorption.
      Dihydrohydroxycinnamic acids and their phase II derivatives, in addition to
      feruloylglycine, showed delayed kinetics due to their colonic origin and
      represented the most abundant group of metabolites (75.7% of total urinary
      metabolites). Dihydrohydroxycinnamate esters (dihydroferuloyl-, dihydrocaffeoyl-
      and dihydrocoumaroylquinic acids) have been identified for the first time in both
      plasma and urine, with microbial origin (excreted 8-12 h after coffee intake)
      amounting to 8% of total urinary metabolites. In conclusion, coffee polyphenols
      are partially bioavailable and extensively metabolized, mainly by the colonic
      microbiota.

PMID- 29177346
TI  - Softening and yielding of soft glassy materials.
AB  - Solids deform and fluids flow, but soft glassy materials, such as emulsions,
      foams, suspensions, and pastes, exhibit an intricate mix of solid- and liquid
      like behavior. While much progress has been made to understand their elastic
      (small strain) and flow (infinite strain) properties, such understanding is
      lacking for the softening and yielding phenomena that connect these asymptotic
      regimes. Here we present a comprehensive framework for softening and yielding of
      soft glassy materials, based on extensive numerical simulations of oscillatory
      rheological tests, and show that two distinct scenarios unfold depending on the
      material's packing density. For dense systems, there is a single, pressure
      independent strain where the elastic modulus drops and the particle motion
      becomes diffusive. In contrast, for weakly jammed systems, a two-step process
      arises: at an intermediate softening strain, the elastic and loss moduli both
      drop down and then reach a new plateau value, whereas the particle motion becomes
      diffusive at the distinctly larger yield strain. We show that softening is
      associated with an extensive number of microscopic contact changes leading to a
      non-analytic rheological signature. Moreover, the scaling of the softening strain
      with pressure suggest the existence of a novel pressure scale above which
      softening and yielding coincide, and we verify the existence of this crossover
      scale numerically. Our findings thus evidence the existence of two distinct
      classes of soft glassy materials - jamming dominated and dense - and show how
      these can be distinguished by their rheological fingerprint.

PMID- 29177347
TI  - Microfluidic production of degradable thermoresponsive poly(N
      isopropylacrylamide)-based microgels.
AB  - Highly monodisperse and hydrolytically degradable thermoresponsive microgels on
      the tens-to-hundreds of micron size scale have been fabricated based on
      simultaneous on-chip mixing and emulsification of aldehyde and hydrazide
      functionalized poly(N-isopropylacrylamide) precursor polymers. The microfluidic
      chip can run for extended periods without upstream gelation and can produce
      monodisperse (<10% particle size variability) microgels on the size range of ~30
      90 MUm, with size tunable according to the flow rate of the oil continuous phase.
      Fluorescence analysis indicates a uniform distribution of each reactive pre
      polymer inside the microgels while micromechanical testing suggests that smaller
      microfluidic-produced microgels exhibit significantly higher compressive moduli
      compared to bulk hydrogels of the same composition, an effect we attribute to
      improved mixing (and thus crosslinking) of the precursor polymer solutions within
      the microfluidic device. The microgels retain the reversible volume phase
      transition behavior of conventional microgels but can be hydrolytically degraded
      back into their oligomeric precursor polymer fragments, offering potential for
      microgel clearance following use in vivo.

PMID- 29177348
TI  - Comprehensive investigations of near infrared downshift and upconversion
      luminescence mechanisms in Yb3+ single-doped and Er3+,Yb3+ co-doped SiO2 inverse
      opals.
AB  - Comprehensive investigations of near infrared (NIR) downshift and visible
      upconversion luminescence (UCL) mechanisms were carried out for Yb3+ single-doped
      and Er3+,Yb3+ co-doped SiO2 inverse opals under excitation at 256, 378, 520 and
      980 nm. NIR emission at 976 nm from the Yb3+-O2- charge transfer state and UCL
      emission at 500 nm due to the cooperative emission of two Yb3+ ions were observed
      in SiO2:Yb3+ inverse opal upon excitation at 256 and 980 nm, respectively. The
      cooperative UCL of two Yb3+ ions was suppressed due to the photon trap created by
      the photonic band gap. For the SiO2:Er3+,Yb3+ inverse opals, NIR emission of Yb3+
      at 976 nm and of Er3+ at 1534 nm were observed upon excitation at 256, 378 and
      520 nm, respectively. Upon excitation at 378 and 520 nm, the 976 nm NIR emission
      of Yb3+ does not arise from (2H11/2/4S3/2) + 2Yb3+(2F7/2) -> Er3+(4I15/2) +
      2Yb3+(2F5/2) traditional quantum cutting. The NIR emission of Yb3+ at 976 nm may
      be due to the Er3+(2H11/2) + Yb3+(2F7/2) -> Yb3+(2F5/2) + Er3+(4I11/2) cross
      relaxation energy transfer process upon excitation at 520 nm. The NIR emission of
      Yb3+ at 976 nm may arise from the cross-relaxation energy transfer of
      Er3+(4G11/2) + Yb3+(2F7/2) -> Yb3+(2F5/2) + Er3+(4F9/2) and Er3+(4F9/2) +
      Yb3+(2F7/2) -> Yb3+(2F5/2) + Er3+(4I13/2) upon excitation at 378 nm.

PMID- 29177349
TI  - Temperature-induced oriented growth of large area, few-layer 2D metal-organic
      framework nanosheets.
AB  - The isolation of few-layer two-dimensional (2D) metal-organic framework (MOF)
      sheets has been achieved at an elevated solvothermal reaction temperature. The 2D
      porphyrin paddlewheel framework-1 (PPF-1) MOF nanosheets (NS) are ultrathin (2.5
      nm) and have large lateral dimensions (over 2 MUm). The yield of PPF-1 NS was
      also increased to 71.7% with increasing the reaction temperature. The results
      revealed that the formation of PPF-1 NS was attributed to the enlarged interlayer
      space and accelerated crystal growth rate along the lateral direction.

PMID- 29177350
TI  - Chalcogenide substitution in the [2Fe] cluster of [FeFe]-hydrogenases conserves
      high enzymatic activity.
AB  - [FeFe]-Hydrogenases efficiently catalyze the uptake and evolution of H2 due to
      the presence of an inorganic [6Fe-6S]-cofactor (H-cluster). This cofactor is
      comprised of a [4Fe-4S] cluster coupled to a unique [2Fe] cluster where the
      catalytic turnover of H2/H+ takes place. We herein report on the synthesis of a
      selenium substituted [2Fe] cluster [Fe2{MU(SeCH2)2NH}(CO)4(CN)2]2- (ADSe) and its
      successful in vitro integration into the native protein scaffold of [FeFe]
      hydrogenases HydA1 from Chlamydomonas reinhardtii and CpI from Clostridium
      pasteurianum yielding fully active enzymes (HydA1-ADSe and CpI-ADSe). FT-IR
      spectroscopy and X-ray structure analysis confirmed the presence of structurally
      intact ADSe at the active site. Electrochemical assays reveal that the selenium
      containing enzymes are more biased towards hydrogen production than their native
      counterparts. In contrast to previous chalcogenide exchange studies, the S to Se
      exchange herein is not based on a simple reconstitution approach using ionic
      cluster constituents but on the in vitro maturation with a pre-synthesized
      selenium-containing [2Fe] mimic. The combination of biological and chemical
      methods allowed for the creation of a novel [FeFe]-hydrogenase with a [2Fe2Se]
      active site which confers individual catalytic features.

PMID- 29177351
TI  - What factors determine the stability of a weak protein-protein interaction in a
      charged aqueous droplet?
AB  - Maintaining the interface of a weak transient protein complex transferred from
      bulk solution to the gaseous state via evaporating droplets is a critical
      question in the detection of the complex association (dissociation) constant by
      using electrospray ionization mass spectrometry (ESI-MS). Here we explore the
      factors that may affect the stability of a protein-protein interaction (PPI)
      using atomistic molecular dynamics (MD) modelling of a complex of ubiquitin (Ub)
      and the ubiquitin-associated domain (UbA) (RCSB PDB code ) and a non-covalent
      complex of diubiquitin (RCSB PDB code ) in aqueous droplets. A general method is
      presented to determine the protonation states of the complexes we investigate in
      particular, and that of a protein in general, under various pH conditions that an
      evaporating droplet acquires due to its change in size. We find that the
      combination of high temperature and high charge states of the protein complexes
      may destabilize the interface by creating new interfaces instead of a direct
      rupture of the initial stable interface. We provide evidence that highly charged
      protein complexes are found in droplets that form conical extrusions of the
      solvent on the surface due to charge-induced instability. This distinct droplet
      morphology leads to a higher solvent evaporation rate that assists in
      transferring the complex in the gaseous state without dissociation. The conical
      solvent protrusions expose on the droplet surface certain amino acids that
      otherwise would be solvated in a droplet with the protein complex of low charge
      states. The new vapor-protein interface does not have a direct effect on the
      stability of the PPI. A common way in experiments to stabilize the protein
      complexes in droplets is to reduce the protonation state of the proteins. Here we
      find that weakly bound protein complexes even at high protonation states can be
      stabilized by the presence of a small number of counterions, without affecting
      the protonation state of the protein. Our findings may provide guiding principles
      in ESI-MS experiments to stabilize weak transient PPIs.

PMID- 29177352
TI  - O2 activation at a trispyrazolylborato nickel(ii) malonato complex.
AB  - To support mechanistic inferences made for an iron-based dioxygenase model, a
      nickel analogue, i.e. a TpNi-malonate (1) was prepared. 1 proved to represent a
      rare case of a nickel complex reacting with O2 in a controlled manner -
      mechanistically different from the iron case - and leads to hydroxylation of the
      malonate.

PMID- 29177353
TI  - Switch-on fluorescent/FRET probes to study human histidine triad nucleotide
      binding protein 1 (hHint1), a novel target for opioid tolerance and neuropathic
      pain.
AB  - Histidine Triad Nucleotide Binding Protein 1 (Hint1) has emerged to be an
      important post-synaptic protein associated with a variety of central nervous
      system disorders such as pain, addiction, and schizophrenia. Recently, inhibition
      of histidine nucleotide binding protein 1 (Hint1) with a small nucleoside
      inhibitor has shown promise as a new therapeutic strategy for the treatment of
      neuropathic pain. Herein, we describe the first rationally designed small
      molecule switch-on probes with dual fluorescence and FRET properties to study
      Hint1. Two non-natural fluorescent nucleosides with a fluorescent lifetime of 20
      and 25 ns were each coupled through a linker to the indole ring, i.e. probes 7
      and 8. Both probes were found to be water soluble and quenched intramolecularly
      via photoinduced electron transfer (PET) resulting in minimal background
      fluorescence. Upon incubating with Hint1, compound 7 and 8 exhibited a 40- and 16
      fold increase in the fluorescence intensity compared to the control. Compounds 7
      and 8 bind Hint1 with a dissociation constant of 0.121 +/- 0.02 and 2.2 +/- 0.36
      MUM, respectively. We demonstrate that probe 8 exhibits a switch-on FRET property
      with an active site tryptophan residue (W123). We show the utility of probes in
      performing quantitative ligand displacement studies, as well as in selective
      detection of Hint1 in the cell lysates. These probes should be useful for
      studying the dynamics of the active site, as well as for the development of
      fluorescence lifetime based high throughput screening assay to identify novel
      inhibitors for Hint1 in future.

PMID- 29177354
TI  - Functionalized graphene sheets for intracellular controlled release of
      therapeutic agents.
AB  - Since therapeutic agents target specific compartments inside the cells, their
      efficiency depends on their intracellular release from drug delivery systems
      (DDS). However, control over the intracellular release of therapeutic agents is a
      challenging issue and can only be achieved by governing their interactions with
      the DDS. In this work, polyglycerol amine- and polyglycerol sulfate
      functionalized graphene sheets as positively and negatively charged 2D
      nanomaterials with 150 nm lateral size were used to deliver and control the
      release of doxorubicin (DOX) inside cells. A pH-sensitive dye was conjugated onto
      the surfaces of graphene sheets and used as an antenna to obtain specific signals
      from the acidic cell compartments. It was found that both positively and
      negatively charged graphene sheets undergo similar acidification processes after
      cellular uptake. Nevertheless, the intracellular drug release of these DOX-loaded
      nanomaterials was distinctly different. As an overall effect of the pi-pi
      stacking and electrostatic interactions, the release of DOX from the positively
      charged graphene sheets was much faster than that from their analogs with a
      negative surface charge. Therefore, therapeutic efficiency in the first case was
      much higher than that in the latter. Based on our findings, the intracellular
      release of drugs from the surfaces of graphene sheets can be finely tuned by
      manipulating their functionalities, which is of great importance in the designing
      of the future graphene-based nanomedicines.

PMID- 29177355
TI  - Nanoparticles grown from methanesulfonic acid and methylamine: microscopic
      structures and formation mechanism.
AB  - Mechanisms of particle formation and growth in the atmosphere are of great
      interest due to their impacts on climate, health and visibility. However, the
      microscopic structures and related properties of the smallest nanoparticles are
      not known. In this paper we pursue computationally a microscopic description for
      the formation and growth of methanesulfonic acid (MSA) and methylamine (MA)
      particles under dry conditions. Energetic and dynamics simulations were used to
      assess the stabilities of proposed model structures for these particles. Density
      functional theory (DFT) and semi-empirical (PM3) calculations suggest that (MSA
      MA)4 is a major intermediate in the growth process, with the dissociation
      energies, enthalpies and free energies indicating considerable stability for this
      cluster. Dynamics simulations show that this species is stable for at least 100
      ps at temperatures up to 500 K, well above atmospheric temperatures. In order to
      reach experimentally detectable sizes (>1.4 nm), continuing growth is suggested
      to occur via clustering of (MSA-MA)4. The dimer (MSA-MA)4(MSA-MA)4 may be one of
      the smaller experimentally measured particles. Step by step addition of MSA to
      (MSA-MA)4, is also a likely potential growth mechanism when MSA is excess. In
      addition, an MSA-MA crystal is predicted to exist. These studies demonstrate that
      computations of particle structure and dynamics in the nano-size range can be
      useful for molecular level understanding of processes that grow clusters into
      detectable particles.

PMID- 29177356
TI  - Facile synthesis of Mn-Fe/CeO2 nanotubes by gradient electrospinning and their
      excellent catalytic performance for propane and methane oxidation.
AB  - Nanotubes have been the focus of vital efforts in the catalysis community because
      of their unique properties. However, owing to the limitations of synthetic
      methods, most multi-element oxides have rarely been fabricated. In this study, we
      design a gradient electrospinning method for the controllable synthesis of Mn
      Fe/CeO2 nanocatalysts and their application in the combustion of propane and
      methane. The strategy is rational, and the nanostructure of Mn-Fe/CeO2 can be
      tuned by simply adjusting the weight ratio of polyvinyl pyrrolidone
      (PVP)/polyacrylonitrile (PAN) during the electrospinning process. Benefitting
      from its unique structural feature, propane and methane conversions in hollow
      tubular Mn-Fe/CeO2-P1 (mPVP : mPAN = 1 : 1) are more than 90% at 382 and 411 
      degrees C, respectively. The superior propane oxidation performance in Mn-Fe/CeO2
      P1 is associated with its hollow tubular structure, high surface oxygen vacancies
      and excellent low-temperature reducibility.

PMID- 29177357
TI  - One-step fabrication of LSPR-tuneable reconfigurable assemblies of gold
      nanoparticles decorated with biotin-binding proteins.
AB  - Assemblies of gold nanoparticles with chain-like morphologies and new near
      infrared (NIR) localized surface plasmon resonance (LSPR) are obtained by adding
      the biotin-binding proteins avidin, neutravidin or streptavidin to citrate-capped
      nanoparticles. The key idea behind this one-step fabrication method is to
      destabilize the colloids by adding positively charged proteins and/or by making
      their zeta potential less negative. The extent of assembly, and therefore the NIR
      LSPR, can be fine-tuned by varying the concentration of proteins as well as by
      changing the pH of the solution. The resulting nanoparticle clusters can also
      reconfigure into smaller assemblies that absorb less NIR light by adding
      thiolated molecules or by increasing the pH of the solution. This, along with the
      observation that the proteins retain their biotin-binding properties in the
      assemblies, makes the proposed method promising for the development of new
      biosensors and drug delivery platforms capable of self-regulating their optical
      properties as a function of chemical signals in their environment.

PMID- 29177358
TI  - Development of a reactive force field for the Fe-C interaction to investigate the
      carburization of iron.
AB  - The approach of molecular dynamics with Reactive Force Field (ReaxFF) is a
      promising way to investigate the carburization of iron which is pivotal in the
      preparation of desired iron-based materials and catalysts. However, it is a
      challenge to develop a reliable ReaxFF to describe the Fe-C interaction,
      especially when it involves bond rearrangement. In this work, we develop an
      exclusive set of Reactive Force Field (ReaxFF) parameters, denoted RPOIC-2017, to
      describe the diffusion behavior of carbon atoms in the alpha-Fe system. It
      inherited some partial parameters in 2012 (ReaxFF-2012) which are suitable for
      hydrogen adsorption and dissociation. This set of parameters is trained against
      data from first-principles calculations, including the equations of state of
      alpha-Fe, the crystal constant of Fe3C and Fe4C, a variety of periodic surface
      structures with varying carbon coverages, as well as the barriers of carbon
      diffusion in the alpha-Fe bulk and on diverse surfaces. The success in predicting
      the carbon diffusion coefficient and the diffusion barrier using the developed
      RPOIC-2017 potential demonstrates that the performance is superior to that of the
      traditional MEAM potential. The new ReaxFF for the Fe-C interaction developed in
      this work is not only essential for the design of novel iron based materials, but
      could also help understand atomic arrangements and the interfacial structure of
      iron carbides.

PMID- 29177359
TI  - Copper inter-nanoclusters distance-modulated chromism of self-assembly induced
      emission.
AB  - Metal nanoclusters (NCs) have attracted broad attention for their molecular-like
      electronic structures and unique emission properties, but the difficulty in
      controlling emission color greatly limits their application in illumination and
      display. In this work, we demonstrate the capability to control the self-assembly
      induced emission (SAIE) of Cu NCs by modulating the inter-NC distance in the self
      assembly materials, which is capable of tuning the emission color from green to
      red. The inter-NC distance is mainly modulated by controlling the experimental
      variables during the NC self-assembly, such as the species of the solvents and
      ligands, duration of assembly, temperature, and so forth. These experimental
      variables influence the balance of inter-NC weak interactions, thus altering the
      distance of as-assembled NCs. The variation of the inter-NC distance greatly
      influences the photo-physical behavior of Cu NCs, and in particular the ligand-to
      Cu-Cu charge transfer, permitting the tuning of the emission color. As the Cu NCs
      self-assembly materials exhibit strong, stable, and color-tunable SAIE, they are
      employed as the color conversion materials for fabricating white light-emitting
      diodes.

PMID- 29177360
TI  - Enhanced bifunctional fuel cell catalysis via Pd/PtCu core/shell nanoplates.
AB  - Depositing Pt atoms on nanoscale two-dimensional (2D) substrates resulting in the
      exposure of specific crystal facets is an effective strategy for reducing the Pt
      content without compromising the catalytic property. Herein, the Pd/PtCu
      core/shell nanoplates exhibit substantially improved ORR and MOR mass activities,
      8.3 and 3.3 times higher than those of commercial Pt. The present work highlights
      the important role of designing a 2D core/shell nanostructure in enhancing fuel
      cell electrocatalysis.

PMID- 29177361
TI  - Synthetic strategies, diverse structures and tuneable properties of polyoxo
      titanium clusters.
AB  - As one of the most prosperous classes of cluster-based materials reported to
      date, polyoxo-titanium clusters (PTCs) have been closely related to many photo
      activities that broadly impact not only chemical but also energy and
      environmental sciences. In contrast to the well-developed polyoxometalates like
      polyoxotungstates and polyoxomolybdates, there is still large room for the
      development of PTCs. The exploration of crystalline PTC materials originates from
      the molecular model of technically important TiO2 materials but has been greatly
      hindered by their daunting and challenging synthesis. This review firstly
      summarizes the conventional and latest successful synthetic strategies applied to
      improve the poor degree of control of crystallization of PTCs. And attributed to
      the synthetic progress achieved in this area, there is a growing number of PTCs
      with diverse structures known to us, also enabling us to study their bandgap
      engineering and light absorption behaviours at the molecular level. In addition,
      exploitation of their applications in many fields is also under way.

PMID- 29177362
TI  - Improved efficient perovskite solar cells based on Ta-doped TiO2 nanorod arrays.
AB  - Organometal halide perovskite solar cells (PSCs) are nowadays regarded as a
      rising star in photovoltaics. In particular, PSCs incorporating oriented TiO2
      nanorod (NR) arrays as the electron transport layer (ETL) have attracted
      significant attention owing to TiO2 NR's superior electron transport abilities
      and its potential in long-term stable PSCs. In addition to improve the electron
      transport ability of TiO2 NRs, the tuning of the band alignments between the TiO2
      NR array and the perovskite layer is also crucial for achieving efficient solar
      cells. This work describes a facile, one-step, solvothermal method for the
      preparation of tantalum (Ta) doped TiO2 NR arrays for efficient PSCs. It is shown
      that the trace doping with Ta tunes the electronic structure of TiO2 NRs by a
      synergistic effect involving the lower 5d orbitals of the doped Ta5+ ions and the
      reduced oxygen vacancies. The synergistic tuning of the electronic structure
      improves the band alignment at the TiO2 NR/perovskite interface and boosts the
      short-circuit current and the fill factor. By using the optimized doped TiO2 NR
      array as the ETL, a record efficiency of 19.11% was achieved, which is the
      highest among one-dimensional-array based PSCs.

PMID- 29177363
TI  - Self-assembled selenium nanoparticles and their application in the rapid
      diagnostic detection of small cell lung cancer biomarkers.
AB  - By coupling molecular imprinting, chitosan biosorption and TiO2 photocatalysis,
      selenium nanoparticles (Se NPs) were self-assembled in a controlled manner on the
      molecular imprinting sites of zeolite-chitosan-TiO2 microspheres. Se NPs with
      different sizes and areal densities were individually synthesized by controlling
      the rapid adsorption of molecular-imprinted nanocomposites and photocatalytic
      reaction of TiO2 nanoparticles. In order to improve the sensitivity and
      specificity of rapid diagnostic detection, Se NPs were self-assembled again into
      high-order and spherically stable structures with an average size of 80 nm by
      well-defined monomer units, after separation from zeolite-chitosan-TiO2
      microspheres with a stabilizer of 0.3% (v/v) bovine serum albumin. Due to their
      biological activity, spherical-shaped Se NPs were used for dot-blot immunoassays
      with multiple native antigens for rapid serodiagnosis of human lung cancer. The
      sensitivity of the dot immunoassays for detecting progastrin-releasing peptide
      (ProGRP) was 75 pg mL-1. The detection time of colloidal Se dot immunoassays for
      ProGRP was only 5 min. No positive results were observed with other commonly
      potential interfering substances, including carcinoembryonic antigen, alpha
      fetoprotein antigen and BSA. The research presents a simple and green method for
      the reuse of SeO32- and the controlled synthesis of Se NPs for biological and
      medical applications by bioaffinity adsorption and photoreduction.

PMID- 29177364
TI  - Hypertension Management and Prevention: The Devil is Ever in the Details.

PMID- 29177365
TI  - Gender-Specific Reference Charts of Fetal Head Circumference in a Singaporean
      Population.
AB  - INTRODUCTION: With the global outbreak of Zika virus and its association with
      microcephaly, an up-to-date fetal head circumference (HC) nomogram is crucial to
      offer a reference standard in order to make an accurate diagnosis. This study was
      conducted to revise the local fetal HC nomogram. MATERIALS AND METHODS: In this
      retrospective study, ultrasound data was used for construction of the fetal HC
      nomogram from a total of 6155 pregnancies in the ethnic Chinese population with
      low risk profile at KK Women's and Children's Hospital over a 10-year period.
      Regression model was fitted to calculate the mean and standard deviation of HC at
      each gestational age (GA). Comparison of HC between ethnic groups (no significant
      differences) and genders were made. The revised chart was compared with another
      commonly used reference chart (Hadlock). In an independent test population,
      different reference charts were used to estimate number of cases with
      microcephaly. RESULTS: A statistically significant difference of HC between the
      genders was observed across all gestational ages. Gender-specific reference
      charts and equation were computed. Our revised fetal HC chart showed a different
      distribution from the Hadlock chart. Compared with the gender-specific charts,
      the Hadlock HC chart would significantly under-report microcephaly cases in male
      fetuses, and tend to over-report in female fetuses. CONCLUSION: This study
      provides a new set of gender-specific fetal HC charts in the Singaporean
      population for antenatal ultrasound surveillance of microcephaly.

PMID- 29177366
TI  - Glycaemic, Blood Pressure and Low Density Lipoprotein Cholesterol Control in
      Adult Patients with Diabetes in Singapore: A Review of Singapore Literature Over
      Two Decades.
AB  - INTRODUCTION: Diabetes mellitus is a burgeoning global health epidemic, with an
      estimated 422 million people living with diabetes in 2014. The number of adult
      diabetic patients in Singapore is expected to rise to 1 million in 2050. Despite
      advances made in the management of diabetes and improvements in healthcare
      accessibility and delivery, the rate and complications of diabetes (myocardial
      infarction, stroke, kidney failure and lower limb amputation) in Singapore have
      not decreased. Gaps between guidelines and practice have been reported in several
      parts of the world. In this narrative review, we aimed to describe the control of
      diabetes in Singapore over the past 20 years. MATERIALS AND METHODS: We reviewed
      studies describing, or trials intervening in, the glycaemic, blood pressure (BP)
      and low density lipoprotein cholesterol (LDL-C) control of adult diabetic
      patients in Singapore published over the past 20 years (1997-2016). Studies
      selected from comprehensive electronic databases searches were reviewed by 4
      reviewers (2 primary care physicians, 1 diabetologist and 1 public health
      epidemiologist). The GRADE approach was used to evaluate the quality of evidence.
      RESULTS: We included 23 articles involving 257,097 subjects. There were 9
      longitudinal, 12 cross-sectional and 2 case-control studies. All studies reported
      mean/median HbA1c between 7.2%-8.6%. BP ranged between 126.5-144 mmHg (systolic)
      and 70-84 mmHg (diastolic) in 9 studies. Nine studies reported LDL-C between 2.4
      3.3 mmol/L. CONCLUSION: Mirroring global patterns, the glycaemic, BP and LDL-C
      control in adult diabetic patients in Singapore do not appear to be treated to
      target in the majority of patients.

PMID- 29177367
TI  - Is the Human Organ Transplant Act (HOTA) to Blame? Addressing Our Organ Shortage
      from a Public Policy Perspective.

PMID- 29177368
TI  - A Comparison of Once- and Thrice-Weekly Erythropoietin Dosing for the Treatment
      of Anaemia of Prematurity.

PMID- 29177369
TI  - Health-related Quality of Life of Home Ventilated Patients (HoMe V) from a
      Tertiary Hospital in Singapore.

PMID- 29177370
TI  - Occult Acetabular Fractures in the Elderly: A Report of Three Cases and Review of
      Literature.

PMID- 29177371
TI  - Recap of the Knee Cap: A "Leave Alone" Lesion.

PMID- 29177372
TI  - [Health anthropology: a current perspective].

PMID- 29177373
TI  - [Challenges in the health care of international migrants in Chile].
AB  - OBJECTIVES: To investigate the perceptions of primary health workers (PHW) about
      the challenges of health care for migrants. MATERIALS AND METHODS: A qualitative
      multicase study was conducted in eight communes of Chile, using the snowball
      technique, where 101 PHW and local authorities were recruited. Semi-structured
      interviews and focal groups were conducted, achieving information saturation.
      RESULTS: The findings were grouped into two major thematic axes: 1. Technical and
      administrative difficulties, and 2. Perception of cultural barriers. According to
      the PHW, although regulations have been established and health care strategies
      have been generated for the migrant population, these are mostly not stable or
      known to all PHW. They are also not easy to implement in the various realities
      investigated. The absence of records on the number of migrants accessing the
      health system makes it difficult to design specific interventions. Additionally,
      health care has complications, and the PHW do not necessarily have tools that
      allow them to provide a care that is culturally sensitive to the needs of the
      migrant community. CONCLUSIONS: The findings put into question the new challenges
      in health that Chile is facing in the face of the growing migrant population. The
      needs perceived by PHW are: stability and clarity in the regulations in force in
      relation to access and provision of services, training in regulations and the
      concrete way in which they should operate, and sensitization in cultural
      competence.

PMID- 29177374
TI  - [Effects in rats of bee-wax alcohols (D-002) on ulcerative colitis induced by
      dextran sulfate and ethanol].
AB  - OBJECTIVES.: To investigate the effects of D-002, a mixture of 6 high molecular
      weight primary aliphatic alcohols, obtained from beeswax (Apis mellifera), on
      severe inflammatory ulcerative colitis (UC) induced by Dextran sulfate (DSS) and
      ethanol in rats (Ratus ratus). MATERIALS AND METHODS.: Rats were randomly
      distributed in six groups: a zero control to which no damage was caused, and five
      to which the UC was induced: a negative control (vehicle), three treated with D
      002 (25, 100 and 400 mg/kg) and a positive control with sulfasalazine (200 mg/kg)
      (reference substance). Clinical manifestations (body weight variation, diarrhea
      and rectal bleeding), macroscopic and histological damage score, and
      myeloperoxidase (MPO) activity were quantified. RESULTS.: The oral treatment with
      D-002 (25, 100 and 400 mg/ kg) significantly prevented the decrease in body
      weight. The dose of 400 mg/kg reduced the presence of diarrhea and rectal
      bleeding, although its comparison with the negative control only reached
      statistical significance on diarrhea. D-002 (25, 100 and 400 mg/kg) significantly
      reduced the score of macroscopic lesions (40.0; 43.3 and 47.2% inhibition,
      respectively), the histological damage score (31.5; 53.7 and 67.1% inhibition,
      respectively) and the activity of MPO (73.2; 83.6 and 85.0% inhibition,
      respectively), compared to the negative control group. Sulfasalazine
      significantly reduced all variables studied. CONCLUSIONS.: D-002 (25, 100 and 400
      mg/kg) significantly protected the colonic mucosa in rats with severe
      inflammatory UC induced by DSS and ethanol.

PMID- 29177375
TI  - [Economic income in peruvian physicians according to the specialty: A cross
      sectional analysis of the ENSUSALUD 2015].
AB  - OBJECTIVES: To evaluate the relationship between having a medical specialty and
      the monthly income of Peruvian doctors, and to compare the economic incomes among
      areas with higher and lower density of medical doctors in Peru. MATERIALS AND
      METHODS: : We analyzed data of the National Satisfaction Survey of Health Users
      (in Spanish: ENSUSALUD) carried out in Peru in the year 2015. This survey, with a
      national level of inference, was performed on physicians working at health
      facilities in Peru. Monthly income was measured considering all paid activities
      of the physician. Crude and adjusted prevalence ratios (PR and aPR) and their 95%
      confidence intervals (95% CI) were calculated through Poisson regression models
      with robust variance, taking into account the complex sampling of the survey.
      RESULTS: Out of 2 219 Physicians surveyed, 2 154 (97.0%) observations were
      analyzed. The probability of earning > S/5 000 (1 572.3 USD) per month was 29.1%
      for general practitioners; 65.6% for specialists; 63.0% for clinical specialists;
      70.5% for surgeons, and 55.7% for other specialties. Compared to general
      practitioners, physicians with clinical, surgical, and other specialties were
      more likely to earn > S/5 000 per month (aPR = 1.44, 1.49, and 1.26,
      respectively). The probability of earning > S/5 000 was higher in those working
      in departments with low medical density. CONCLUSIONS: Monthly incomes were higher
      for specialist physicians than for non-specialists. Economic incomes were higher
      in departments with lower density of physicians, which may encourage physicians
      to work in these departments.

PMID- 29177376
TI  - [Detection of influenza A, B and subtypes A (H1N1) pdm09, A (H3N2) viruses by
      multiple qrt-pcr in clinical samples].
AB  - OBJECTIVES.: To describe the clinical and epidemiological characteristics of
      patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de
      Salud (INSN) in Lima, Peru; a National Reference Center for this disease.
      MATERIAL AND METHODS: . Observational, descriptive and transversal study. We
      reviewed the clinical histories and laboratory tests of patients diagnosed with
      EB treated in INSN from 1993 to 2015. RESULTS.: 93 patients were registered. The
      average age was 7.9 +/- 5.6 years; 53.8% (n = 50) were boys. Clinical forms
      corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%)
      union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The
      clinical form could not be identified in a case. A total of 48 cases (51.6%) came
      from Lima and Callao, and 45 cases (48.4%) from other provinces of the country.
      Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%),
      odontogenic (87.1%), and nutritional (79.6%) involvement, as well as
      pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition
      (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%).
      CONCLUSIONS.: 93 cases of EB were reported in INSN, the predominant clinical
      presentation was the dystrophic form.

PMID- 29177377
TI  - [Epidermolysis bullosa in peru: clinical and epidemiological study of patients
      treated in a national reference pediatric hospital, 1993-2015].
AB  - OBJECTIVES: To describe the clinical and epidemiological characteristics of
      patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de
      Salud (INSN) in Lima, Peru; a National Reference Center for this disease.
      MATERIALS AND METHODS: Observational, descriptive and transversal study. We
      reviewed the clinical histories and laboratory tests of patients diagnosed with
      EB treated in INSN from 1993 to 2015. RESULTS: 93 patients were registered. The
      average age was 7.9 +/- 5.6 years; 53.8% (n = 50) were boys. Clinical forms
      corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%),
      union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The
      clinical form could not be identified in a case. A total of 48 cases (51.6%) came
      from Lima and Callao, and 45 cases (48.4%) from other provinces of the country.
      Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%),
      odontogenic (87.1%), and nutritional (79.6%) involvement, as well as
      pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition
      (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%).
      CONCLUSIONS: 93 cases of EB were reported in INSN, the predominant clinical
      presentation was the dystrophic form.

PMID- 29177378
TI  - [Progression of chronic renal disease in a reference hospital of social security
      of Peru 2012-2015].
AB  - OBJECTIVES.: To describe the characteristics of the population with chronic
      kidney disease (CKD) stage 3 and 4, to determine the factors associated with CKD
      progression and admission to renal replacement therapy (RRT), as well as renal
      survival. MATERIALS AND METHODS.: Longitudinal retrospective study of patients
      referred between January 2012 and December 2015 to the Renal Health Unit of the
      Hospital Nacional Edgardo Rebagliati Martins (HNERM), who were evaluated and
      followed by a multidisciplinary team. The clinical and laboratory data for each
      query were recorded in a software created specifically for the program. A
      multivariate logistic regression analysis was performed to assess the factors
      associated with the progression of CKD, a Cox regression model to predict the
      risk of entering RRT and the Kaplan-Meier method for renal survival analysis.
      RESULTS.: We assessed 1248 patients in stage 3A: 248 (20%), stage 3B: 548 (44%)
      and stage 4: 452 (36%). 352 (28%) progressed, being proteinuria the most
      important progression factor (OR: 3.2; CI 95%: 2,2-4.6). Proteinuria increases
      the risk of admission to RRT in four times and having a glomerular filtration
      rate < 30% in 3.6 times. Median follow-up was 12 months (RIC 5-27 months). 92
      patients (7%) required to initiate RRT. Renal survival at 12 months of follow-up
      was 96% and at 24 months was 90%. CONCLUSIONS.: Our study shows that in a
      specialized center a significant proportion of patients with CKD does not
      progress in their disease and that the factor that is most associated with
      progression of disease and at the onset of RRT is proteinuria.

PMID- 29177379
TI  - [Clinical-pathological features and survival in young women with cervical cancer:
      a retrospective analysis from the instituto nacional de enfermedades
      neoplasicas].
AB  - OBJECTIVE: To determine the clinical and histological characteristics and
      prognostic factors of cervical cancer (CC) in young Peruvian patients. MATERIALS
      AND METHODS: Retrospective analysis of patients younger than 35 years old
      diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades
      Neoplasicas. RESULTS: 449 patients had epithelial neoplasms. The main
      histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%)
      and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia
      (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also
      identified. 82.3% of the patients presented locally advanced disease. Stages IIB
      (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5%
      (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia,
      tumor size, parametrial involvement and hydronephrosis were factors that affected
      survival. No significant relation was found between histological type and
      survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95%
      confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0
      4.0) were independently associated with survival; likewise, the parametrial
      commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3
      5.3) extension to the pelvic bone. CONCLUSIONS: Cervical cancer in young
      Peruvians is diagnosed in advanced stages. Overall survival in each stage is
      similar to the reported in older patients. The importance of conventional
      prognosis- related factors was confirmed. Anemia was an important independent
      prognostic factor requiring further investigations.

PMID- 29177380
TI  - [Preferences and satisfaction towards a screening program with self-administered
      human papilloma virus detection tests].
AB  - Cross-sectional study describing preferences and satisfaction towards a cervical
      cancer screening program with selfadministered rapid tests for the detection of
      human papillomavirus (HPV). Of 2 090 users picked by the program in Ventanilla
      Callao - Peru, 97 were randomly selected to be surveyed. In addition, interviews
      were conducted with women leaders of the community, in charge of providing the
      evidence. 74.2% of the users felt, at least, satisfied with the program. 68% of
      women prefer to take the test, mainly by demanding less time. Of women who prefer
      to take the test at the Health Center, 90.3% do so for the safety of the test
      being done correctly. The inclusion of community leaders in the program allowed a
      good diffusion of the test and the steps to carry it out.

PMID- 29177381
TI  - [Neonatal meningitis in a general hospital in Lima, Peru, 2008 to 2015].
AB  - Aiming at describing the incidence, clinical characteristics and factors
      associated with neonatal meningitis (NM), a case series study was conducted from
      2008 to 2015, where 53 neonates, 10 with early onset NM and 43 with late onset
      were included. An incidence of 1.5 per thousand live births and a lethality of
      3.8% were found. The associated factors were peripartum fever, urinary tract
      infection and chorioamnionitis (P < 0.05). Frequent symptoms were fever (84.9%),
      hypotonia (77.4%) and hypoactivity (73.6%). In the cerebrospinal fluid (CSF), the
      cases of early NM presented a median of 330 leukocytes/ul and 29 mg/dl of
      glucose, and the cases of late NM presented 170 leukocytes/ul and 32 mg/dl of
      glucose. The most common bacteria were Listeria monocytogenes (16.9%) and
      negative coagulase staphylococcus (11.3%). In conclusion, the incidence was high
      compared to other studies and the associated factors were the expected.

PMID- 29177382
TI  - [High frequency of dyslipidemia in VIH-infected patients in aa peruvian public
      hospital].
AB  - The objective of the study was to determine the frequency and characteristics of
      dyslipidemia in patients with HIV in highly active antiretroviral therapy (HAART)
      in a Peruvian public hospital. A cross-sectional study was carried out in
      patients with complete lipid profile after receiving at least six months of
      HAART. Dyslipidemia was defined according to the criteria of the NCEP-ATP III. We
      reviewed 2 975 clinical histories, and included 538 (18.1%) in the analysis. The
      frequency of dyslipidemia was 74.7%. HAART regimens which include protease
      inhibitors (PI) (odds ratio [OR]: 1.22; confidence interval at 95% [CI 95%]: 1.11
      1.33) and to be older than 40 years (OR: 1.17; CI 95%: 1.05-1.28) were associated
      with dyslipidemia, adjusted by viral load, CD4 lymphocyte level and gender. In
      conclusion, dyslipidemia was very common in our sample and was mainly associated
      with the use of PI. It is necessary to promote the dyslipidemia control as part
      of the comprehensive care of the patient with HIV.

PMID- 29177383
TI  - [Evaluation of Morisky medication adherence scale (mmas-8) in older adults of a
      primary health care center in Chile].
AB  - In order to determine whether the Morisky 8-item medication adherence (MMAS-8) is
      a useful instrument in elderly hypertensive patients attending a primary care
      center, we conducted a field study with a quantitative approach of evaluation of
      diagnostic tests in elderly hypertensive patients from the Cardiovascular Health
      Program Health in Cabrero, Chile. The results of the scale were compared with the
      blood pressure and the pill-count method. The diagnostic evaluation of the scale
      using the reference methods of blood pressure and pill count resulted:
      Sensitivity: 86%, 85%; specificity: 56%, 58%; positive predictive value: 60%,
      65%; negative predictive value: 84%. 81%. In conclusion, the scale allows to
      detect in a simple way, and at a low cost, to people who are not adherent to
      their regimen of drug treatment.

PMID- 29177384
TI  - [Echinococcosis hyper-endemic and cystic fertility in pigs of the inter-andean
      valley of Huancarama, Peru].
AB  - The objective of the research was to determine the percentage of echinococcosis
      infection in swine, cystic fertility and associated factors. Cross-sectional
      study. The population was formed by 579 pigs slaughtered in the slaughterhouse of
      Huancarama. Hydatid cysts were detected by postmortem evaluation. Fertility was
      determined by measuring the diameter of the cysts and microscopically observing
      the germinative membrane in search of protoscoleces. The percentage of cystic
      echinococcosis infection was 76.7% (CI 95%: 73.2-80.3). Pigs older than two years
      were more likely to have cysts (RP 1.03; CI 95%: 1.0-1.1; (P < 0.01), as well as
      those coming from the Andahuaylas district (RP 1.2; CI 95%: 1.1-1.4; P < 0.01).
      Lung cysts showed a lower percentage of infection than hepatic ones. We examined
      346 hydatid cysts of 334 pigs, a total fertility of 42.8% was found (CI 95%: 37.4
      48.1).

PMID- 29177385
TI  - [Psychometric analysis of a questionnaire to measure the educational environment
      in a sample of medical students in Peru].
AB  - The objective of the study was to determine the psychometric properties of the
      Dundee Ready Education Environment Measure (DREEM) questionnaire in students of a
      Peruvian medical school. Participants were first-to-sixth-year students, invited
      to participate through a web platform. In the analysis the alpha coefficient of
      Cronbach was used to evaluate internal consistency. In addition, a confirmatory
      factorial analysis was performed to evaluate the construct validity of the
      subscales of the DREEM. The adjustment quality indexes used were: Root Mean
      Square Error Approximation (RMSEA), the Index of Benchmarking (CFI), Tucker-Lewis
      Index (TLI), and the Standardized Root Mean Residual (SRMR). The results showed
      that the social self-perception dimension had an alpha of Cronbach of less than
      0.70. In addition, the quality indices did not support the five-dimensional
      structure of the DREEM. In conclusion, the DREEM questionnaire did not perform
      optimally in this Peruvian sample.

PMID- 29177386
TI  - [Klebsiella pneumoniae NEW DELHI METALO-LACTAMASE IN A PERUVIAN NATIONAL
      HOSPITAL].
AB  - The emergence of Enterobacteria producing carbapenemases of type New Delhi Metalo
      beta-lactamases (NDM), >represent, today, a real problem of world public health.
      The presence of this resistance mechanism limits or nullifies the therapeutic
      options to combat these bacteria. In Latin America, the figures are getting
      higher, as they are reported in Guatemala, Colombia, Chile, Argentina, among
      others. Peru has not, to date, described the presence of this resistance pattern;
      however for several years it has been presumed to exist. Nine cases of Klebsiella
      pneumoniae NDM are described, as infectious or colonizing agents, in critically
      ill patients, mostly with neurosurgical pathology, of Hospital Nacional Dos de
      Mayo in Lima - Peru. The patients in the series described below represent the
      first reports of Klebsiella pneumoniae NDM in Peru.

PMID- 29177387
TI  - [Prevalence of antibodies to rickettsias and ehrlichias in four border
      departments of Peru].
AB  - To determine the prevalence of antibodies to Rickettsia and Ehrlichia, related to
      recent and past contact, in the border towns of the departments Loreto, Madre de
      Dios, Tumbes and Tacna, during the years 2010 and 2011, surveys for serological
      evaluation were carried out using the indirect immunofluorescence assay (IIF), in
      order to detect immunoglobulins G (IgG) and Total immunoglobulins (IgA + IgM +
      IgG) in 1634 persons. A recent contact prevalence was found for Ehrlichia of 3.7%
      (CI 95%: 3.0-4.4) and for Rickettsia of 10.6% (CI 95%: 9.1-12.1), and past
      contact for Ehrlichia of 19.0% (CI 95%: 17.1-21.0) and for Rickettsia of 23.3%
      (CI 95%: 21.2-25.3). It is concluded that there is a higher prevalence for past
      contact or infection in the population studied, both for Rickettsia and
      Ehrlichia, which would indicate an endemic behavior to both infectious agents in
      the geographic areas mentioned.

PMID- 29177388
TI  - [Risk and health of adolescents in the valley of the Apurimac, Ene and Mantaro
      rivers in Peru].
AB  - The article presents the diagnosis of the living conditions of male and female
      adolescents in the area of the valley of the Apurimac, Ene and Mantaro rivers (in
      Spanish: VRAEM), who are exposed to situations of risk and social and sexual
      vulnerability and sexual due to the high levels of coca-leaf production and the
      context of the illegal drug trade which create the illusion of rapid social
      ascent. From this, it is necessary to ask: what are the living conditions and
      risk situations of adolescents in the VRAEM? And, what are the alternatives for
      an improvement of their situation from access to education and health care
      programs? This risk situation is the result of unequal gender relations, sexual
      violence, school dropout, teen pregnancy, alcohol and drug use, as well as of the
      lack of opportunities as a result of the participation in coca economy and
      illegal drug trade among adolescents in the VRAEM. Finally, we present the
      results of the attention of professionals of the health centers to promote
      counseling on sexual and reproductive health and access to health services of the
      Adolescent Life Program Life, as an opportunity to link the contents of the
      education curriculum and the compliance targets of this sector, highlighting the
      need of an approach of multiculturalism and gender equality in the access to
      health and education of adolescents.

PMID- 29177389
TI  - [Between the acclimatization to high altitude, the medical anthropology and the
      civilizing utopia. Mapping of the evolution of thought of Carlos Monge Medrano on
      the health-illness process of andean populations].
AB  - The main objective of this study is to describe how the ideas of Carlos Monge
      respect to high altitude sickness developed and how these were being deployed in
      the framework of the discussions on the living conditions of indigenous
      populations in the period 1928-1963. I postulate that the form how the Monge's
      paradigm was proposed, the tensions produced by various alternative movements and
      the way these contradictions were resolved were central, both for the subsequent
      development of different scientific disciplines and for their different
      institutional expressions in Peru. In addition, this article describes the
      evolutionary trajectory of Monge's ideas about the adaptation of indigenous
      populations to high altitude and the discussions that emerged with other research
      groups around the consumption of coca leaf. It also presents an analysis of the
      limitations of the biomedical view regarding the health of the Andean
      populations, a view that was progressively influenced by the changing social and
      political scenario in the context of the Cold War.

PMID- 29177390
TI  - [Hospital San Juan de Dios: actor and victim of the public policies in Colombia].
AB  - In this article, we narrate and analyze the historical configuration that a group
      of female workers and a collective of social organizations made about the
      Hospital San Juan de Dios (HSJD) and Instituto Materno Infantil (IMI) in Bogota,
      Colombia, within the neoliberal crisis in health. Our ethnographic research
      intersects the Latinamerican traditions of collaborative ethnography and historic
      anthropology. The research was conducted in two sites. In the first one, from
      2005 until 2015, we had informal conversations and conducted workshops and semi
      structured interviews with IMI workers. The second site corresponds to our
      participation in the deliberations of the Mesa Juridica por el San Juan de Dios
      (2008-2009), which aimed to elevate a class action to defend the hospitals. We
      found that workers and social organizations made use of the colonial origin of
      the hospitals and their institutionalization as center of welfare policies in the
      country as a way to highlight their patrimonial, historical, educational and
      social importance. This historical construction critiques efforts that negate or
      transform the public character of the hospitals and helped them carry on
      different actions to denounce the neoliberal health care reform as the cause of
      the hospitals most important crisis and closing. The different actors denounce
      the change in the hospitals-state relationship, which transited from being
      central for the development of social policies to reflecting a symbolic and
      material elimination of the hospitals. Such transition benefits the market
      interests established by the neoliberal model.

PMID- 29177391
TI  - [Intercultural health: The life cycle stages in the Andes].
AB  - The most relevant theories and ideas about the life cycle in the Andes and their
      relationship with human development and health are presented. The life cycle is
      not an immutable phenomenon, the number of stages and its meaning is historically
      and culturally based. A comparative analysis with the theory of Freud and Erikson
      was made. It is concluded that the contribution of Andean culture focuses on: 1)
      Each stage of human development is associated with productive and reproductive
      processes of life in relation, as well as an adequate balance between rights and
      duties in life in society; 2) The couple is the basic social unit, and not the
      individual. It is a contribution to the design of health interventions with an
      intercultural approach.

PMID- 29177392
TI  - [Tuberculosis in Peru: epidemiological situation, progress and challenges for its
      control].
AB  - Tuberculosis (TB) is the first cause of death by an infectious agent in the
      world, the incidence in the population is declining very slowly and drug
      resistance is currently considered an international crisis. In Peru, the recent
      TB Prevention and Control Act in Peru (Law 30287) declares the fight against TB
      of national interest. In recent years, the Ministry of Health's (MINSA) National
      Health Strategy for the Prevention and Control of Tuberculosis (ESNPCT) has
      achieved significant progress in the control of this disease; however, challenges
      still remain to be addressed. This article reviews the epidemiological situation
      of TB in Peru, systematizes the progress achieved during the management of the
      ESNPCT >team between the years 2011 and 2015 from the biomedical approach, public
      management and social determinants of health, also posing challenges to achieving
      TB control under law 30287 and the "End of TB" strategy of the World Health
      Organization (WHO).

PMID- 29177393
TI  - [Informed and empowered citizens: Keys to the full exercise of health rights].
AB  - Currently, there is a Peruvian legal framework that promotes the dissemination of
      information on the health rights of the population. Institutions have been
      created, such as the National Superintendence of Health, which are in charge of
      promoting health rights and supervising health-care providers. Despite many
      achievements, such as extending comprehensive health insurance coverage, it is
      necessary to implement strategies for the population to access information and
      advice in a timely, quick and complete manner. Some experiences have shown
      potential for expansion and growth, such as citizens' participation in Health
      Service User Councils and the Program of Integrated Actions for the Promotion of
      Health Rights, as well as the formation of decentralized Intendencies of the
      National Superintendency of Health. The conciliation and arbitration centers, the
      training of community health agents, the citizen vigilance, and even innovative
      strategies using information and communication technologies such as free
      smartphone applications, are important mechanisms for citizens to have more
      information and knowledge in health, and thus, to be more empowered, having the
      capacity to exert more control over the decisions taken on their health.

PMID- 29177394
TI  - [Syndromic approach for the diagnosis and management of acute febrile infestious
      diseases in emergencies].
AB  - Several of the acute diseases with infectious etiology (viral, bacterial or
      parasitic) initially start with a syndrome which can be febrile, febrile icteric,
      febrile hemorrhagic, febrile with respiratory manifestations, febrile with
      neurological impairment, febrile with dermal eruptions, febrile anemic,
      diarrheal, necrotic cutaneous ulcer, or deaths of febrile patients may occur
      without a defined diagnosis, with some variants according to the ecological
      social niche in which they occur; the syndromic approach is important, to quickly
      classify the case or the outbreak and thus have an appropriate and timely
      diagnosis that allows to orient both the individual management and the prevention
      and control measures in the population, even if there are limitations for the
      diagnosis of all the cases. This article describes the syndromic approach, the
      syndromes of importance in public health (collective) and their approach, all
      this is important because of its presentation in outbreaks that are occurring in
      the various ecological niches of our country, exacerbated by climate change.

PMID- 29177395
TI  - [Infection by the Mycobacterium avium-intracellulare complex in patients with
      HIV/AIDS in a Peruvian hospital: A series of cases].
AB  - There is little information on the presence of the Mycobacterium avium
      Intracellulare (MAC) complex in Peru. Five cases of MAC infection are described
      in patients with HIV/AIDS at the National Hospital Dos de Mayo, Lima - Peru. The
      patients presented, mainly, persistent fever, chronic diarrhea, consumptive
      syndrome, pancytopenia and citofagocitosis. In all of them, resistant acid
      alcohol bacilli were identified in feces, so they received antituberculous
      treatment. The culture of feces was negative for Mycobacterium tuberculosis and,
      later, in all cases MAC was identified using a molecular test (genotype) in the
      culture of feces. Three patients received treatment for MAC right after
      identification; however, they all died. Before presentations similar to the
      reported, we suggest the use of higher performance methods (blood culture,
      myeloculture, molecular tests), as well as early associating drugs with activity
      for MAC to antitubercular scheme with the intention of improving the prognosis of
      this group of patients.

PMID- 29177396
TI  - [Co-infection by Mycobacterium fortuitum and Mycobacterium tuberculosis in
      splenic abscesses in a patient with HIV].
AB  - Patients with HIV are susceptible to mycobacterium infection. In the case of fast
      growing mycobacteria, the group to which Mycobacterium fortuitum (M. fortuitum)
      belongs, infections have been described in the skin, lungs, lymph nodes and
      disseminated disease. We present the case of a 43-year-old male patient with pre
      diagnosis of HIV in antiretroviral therapy, which comes as a fever, asthenia,
      weight loss and chronic diarrhea. Abdominal tomography is performed and
      hepatosplenomegaly is evidenced with nodular lesions in the spleen. The splenic
      culture was finally positive for M. Fortuitum, with positive PCR to Mycobacterium
      tuberculosis. The current treatment protocols for this type of infection are
      based on the susceptibility shown in the cultures performed. With regard to
      coinfections between M. Fortuitum and Mycobacterium tuberculosis, in HIV positive
      patients, there are even less information.

PMID- 29177397
TI  - [Not everything is Zika: congenital toxoplasmosis, still prevalent in Colombia?]
AB  - Congenital toxoplasmosis continues to be a public health threat. Even existing
      guidelines, publicly known, its implementation and lack of appropriate
      interpretation of serological tests in pregnancy is often observed. This leds to
      failure in opportunities for positive and known interventions to decrease the
      fetal risk due to Toxoplasma gondii infection. We reported herein a case series,
      with variable neurological and systemic compromise (respiratory distress,
      hepatosplenomegaly, enterocolitis, brain calcifications, thrombocytopenia,
      ascites, shock), even fatal, calling for awareness about the fact that despite
      the Zika epidemics in 2015-2016 in Brazil, Colombia and other countries,
      precisely toxoplasmosis, is a differential diagnosis still prevalent in these
      territories, that can leds to severe consequences, with neurological disability
      and risk of ocular damage, even lately. Additionally, with varieties of T. gondii
      with more aggressive patterns in Latin America, which make worse those cases,
      including also a higher risk of death.

PMID- 29177398
TI  - [Taki Onqoy: mercury poisoning epidemic in 16TH century Huamanga].
AB  - Taki Onqoy is a syndrome that corresponds to the poisoning from exposure to
      mercury. It appeared as a result of the exploitation of the mercury mines of
      Paras and Huancavelica in Peru during the 16th century. The Cachexia mercurial,
      the last stage of the disease, would be associated with the idea of pishtaco. The
      Taki Onqoy in 16th-century Peru represents the largest epidemic of mercury
      poisoning known to humanity.

PMID- 29177399
TI  - [Pharmaceutical counseling and adherence to antihypertensive treatment:
      Preliminary study].

PMID- 29177400
TI  - [Verrucous cutaneous leishmaniasis: unusual presentation].

PMID- 29177401
TI  - [Situational diagnosis of primary immunodeficiencies: Preliminary approximation].

PMID- 29177402
TI  - [Stigma related to HIV/AIDS and adherence to antiretroviral therapy].

PMID- 29177403
TI  - [Stigma related to HIV/AIDS and adherence to antiretroviral therapy - reply].

PMID- 29177404
TI  - [Tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: an
      unattended need].

PMID- 29177405
TI  - [About the taxonomic and systematic nomenclature of apicomplejos].

PMID- 29177406
TI  - Cardiovascular disease statistics from the European atlas: inequalities between
      high- and middle-income member countries of the ESC.

PMID- 29177407
TI  - A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine:
      Effects on Mortality and Measles Antibody Levels.
AB  - Background: In addition to protecting against measles, measles vaccine (MV) may
      have beneficial nonspecific effects. We tested the effect of an additional early
      MV on mortality and measles antibody levels. Methods: Children aged 4-7 months at
      rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau
      were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb
      strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis
      hepatitis B-Haemophilus influenzae type b vaccine. All children received routine
      MV at 9 months. We assessed mortality through home visits and compared mortality
      from enrollment to age 3 years using Cox proportional hazards models, censoring
      for subsequent nontrial MV. Subgroups of participants had blood sampled to assess
      measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012
      to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person
      years). The mortality was lower than anticipated and did not differ by
      randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At
      enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea
      Bissau had protective measles antibody levels. By age 9 months, no measles
      unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early
      MV recipients had protective levels. At final follow-up, 98% (186/189) in the
      early MV group and 97% (196/202) in the control group had protective levels.
      Conclusions: Early MV did not reduce all-cause mortality. Most children were
      susceptible to measles infection at age 4-7 months and responded with high
      antibody levels to early MV. Clinical Trials Registration: NCT01644721.

PMID- 29177408
TI  - Organizing and implementing a multidisciplinary fast track oncology clinic.
AB  - Quality problem: Patients with gastrointestinal malignancies often need multiple
      appointments with different medical specialists, causing waiting times to accrue.
      Initial assessment: In our hospital, care is organized in a sequential manner,
      causing long waiting times. To reduce this, a fast track outpatient clinic (FTC)
      was implemented. Choice of solution: The FTC was organized within the hospital's
      existing structure. Patient centered care was achieved by ensuring that the
      medical specialists visit the patient, implementing nurse coordinators and
      considering patient wishes and co-morbidities when formulating a treatment plan.
      Implementation: A mandate from the board (Top-down), ensured cooperation between
      different medical departments and a change in resource allocation (i.e. medical
      staff); a horizontal clinic across a vertical departmental structure. Brainstorm
      sessions between the departments led by two physicians who were going to work at
      the FTC (Bottom-up), assured a swift implementation of the FTC. Evaluation: Since
      implementation in 2009, patient influx has tripled. Waiting time for an
      appointment and start of treatment was reduced from 2-4 weeks to 6 working days
      and from 12-14 weeks to 17 working days, respectively. This was achieved by re
      allocating recourses, but without increasing existing resources. Lessons learned:
      The combination of a top-down and bottom-up strategy ensured participation from
      all involved departments, a strong foundation and a shared vision on patient
      centered care. The FTC facilitates sharing information between different medical
      specialists through both proximity and a shared electronic patient record. The
      implementation of the FTC comprises a change in organization, but not a change in
      structure.

PMID- 29177409
TI  - Barriers and facilitators related to the implementation of a physiological track
      and trigger system: A systematic review of the qualitative evidence.
AB  - Purpose: To identify the barriers to, and facilitators of, the implementation of
      physiological track and trigger systems (PTTSs), perceived by healthcare workers,
      through a systematic review of the extant qualitative literature. Data sources:
      Searches were performed in PUBMED, CINAHL, PsycInfo, Embase and Web of Science.
      The reference lists of included studies were also screened. Study selection: The
      electronic searches yielded 2727 papers. After removing duplicates, and further
      screening, a total of 10 papers were determined to meet the inclusion criteria
      and were reviewed. Data extraction: A deductive content analysis approach was
      taken to organizing and analysing the data. A framework consisting of two
      overarching dimensions ('User-related changes required to implement PTTSs
      effectively' and 'Factors that affect user-related changes'), 5 themes (staff
      perceptions of PTTSs and patient safety, workflow adjustment, PTTS,
      implementation process and local context) and 14 sub themes was used to classify
      the barriers and facilitators to the implementation of PTTSs. Results of data
      synthesis: Successful implementation of a PTTS must address the social context in
      which it is to be implemented by ensuring that the users believe that the system
      is effective and benefits patient care. The users must feel invested in the PTTS
      and its use must be supported by training to ensure that all healthcare workers,
      senior and junior, understand their role in using the system. Conclusion: PTTSs
      can improve patient safety and quality of care. However, there is a need for a
      robust implementation strategy or the benefits of PTTSs will not be realized.

PMID- 29177411
TI  - Ultrasmall Superparamagnetic Iron Oxide Imaging Identifies Tissue and Nerve
      Inflammation in Pain Conditions.
AB  - Objective: Correlation between radiologic structural abnormalities and clinical
      symptoms in low back pain patients is poor. There is an unmet clinical need to
      image inflammation in pain conditions to aid diagnosis and guide treatment.
      Ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle, is
      clinically used to treat iron deficiency anemia and showed promise in imaging
      tissue inflammation in human. We explored whether ferumoxytol can be used to
      identify tissue and nerve inflammation in pain conditions in animals and humans.
      Methods: Complete Freud's adjuvant (CFA) or saline was injected into mice hind
      paws to establish an inflammatory pain model. Ferumoxytol (20 mg/kg) was injected
      intravenously. Magnetic resonance imaging (MRI) was performed prior to injection
      and 72 hours postinjection. The changes in the transverse relaxation time (T2)
      before and after ferumoxytol injection were compared between mice that received
      CFA vs saline injection. In the human study, we administered ferumoxytol (4
      mg/kg) to a human subject with clinical symptoms of lumbar radiculopathy and
      compared the patient with a healthy subject. Results: Mice that received CFA
      exhibited tissue inflammation and pain behaviors. The changes in T2 before and
      after ferumoxytol injection were significantly higher in mice that received CFA
      vs saline (20.8 +/- 3.6 vs 2.2 +/- 2.5, P = 0.005). In the human study,
      ferumoxytol-enhanced MRI identified the nerve root corresponding to the patient's
      symptoms, but the nerve root was not impinged by structural abnormalities,
      suggesting the potential superiority of this approach over conventional
      structural imaging techniques. Conclusions: Ferumoxytol-enhanced MRI can identify
      tissue and nerve inflammation and may provide a promising diagnostic tool in
      assessing pain conditions in humans.

PMID- 29177410
TI  - Relationship of acid-base status with arterial stiffness in community-living
      elders: the Health ABC Study.
AB  - Background: Animal studies suggest that acidosis protects against arterial
      calcification, which contributes to arterial stiffness. The goal of this study
      was to investigate the associations of serum bicarbonate and pH with arterial
      stiffness in community-living older adults. Methods: We performed cross-sectional
      analyses among 1698 well-functioning participants 70-79 years of age. Bicarbonate
      and pH were measured by arterialized venous blood gas at the point of care.
      Bicarbonate was categorized into low (<23 mEq/L), normal (23-27.9) and high
      (>=28). Arterialized venous pH (AVpH) was categorized into tertiles: <=7.40,
      >7.40-7.42 and >7.42. Arterial stiffness was evaluated by pulse wave velocity
      (PWV) and high ankle-brachial index (ABI; >1.3/incompressible). We used linear
      and logistic regression to evaluate the association of bicarbonate and AVpH with
      PWV and high ABI, respectively. Results: The mean age was 76 years and 15% had an
      estimated glomerular filtration rate (eGFR)  <60 mL/min/1.73 m 2 . The mean
      bicarbonate was 25.2 +/- 2.1 mEq/L and the mean AVpH was 7.41 +/- 0.03. Compared
      with participants in the normal bicarbonate category, those in the low
      bicarbonate group had 8.8% higher PWV (P = 0.006) and 1.87 greater odds of high
      ABI (P = 0.04). However, the associations were not significant after adjusting
      for eGFR (P = 0.24 and 0.43, respectively). There was no difference in PWV or
      high ABI across AVpH tertiles. Results were similar in those with and without
      chronic kidney disease and after excluding participants on diuretics.
      Conclusions: We did not observe an independent association of bicarbonate or AVpH
      with arterial stiffness measured by high PWV or ABI in community-living older
      individuals. Future studies evaluating patients with a greater severity of
      chronic kidney disease and with more extreme alterations in acid-base status are
      warranted.

PMID- 29177412
TI  - Prefrontal Recruitment Mitigates Risk-Taking Behavior in Human Immunodeficiency
      Virus-Infected Young Adults.
AB  - Background: Human immunodeficiency virus (HIV)-infected (HIV+) young adults often
      engage in risk-taking behavior. However, the disruptive effects of HIV on the
      neurobiological underpinnings of risky decision making are not well understood.
      Methods: Risky decision making, measured via the Iowa Gambling Task (IGT), was
      compared voxel-wise to resting cerebral blood flow (rCBF) acquired via arterial
      spin labeling. Separate topographical maps were obtained for HIV-uninfected (HIV
      ; n = 62) and HIV+ (n = 41) young adults (18-24 years old) and were compared to
      the full cohort of participants. For the HIV+ group, rCBF was compared to recent
      and nadir CD4. Results: IGT performance was supported by rCBF in 3 distinct brain
      regions: regions I, II, and III. The relationship between IGT performance and
      rCBF in HIV+ individuals was most robust in region I, the ventromedial prefrontal
      and insular cortices. Region II contained strong relationships for both HIV- and
      HIV+. Region III, dorsolateral prefrontal and posterior cingulate cortices,
      contained relationships that were strongest for HIV- controls. IGT performance
      was intact among HIV+ participants with higher rCBF in either region I or region
      III. By contrast, performance was worse among HIV+ individuals with lower rCBF in
      both regions I and III when compared to HIV- controls (P = .01). rCBF in region
      III was reduced in HIV+ compared with HIV- individuals (P = .04), and positively
      associated with nadir CD4 cell count (P = .02). Conclusions: Recruitment of
      executive systems (region III) mitigates risk-taking behavior in HIV+ and HIV-
      individuals. Recruitment of reward systems (region I) mitigates risk-taking
      behavior when region III is disrupted due to immunological compromise.
      Identifying individual recruitment patterns may aid anatomically directed
      therapeutics or psychosocial interventions.

PMID- 29177413
TI  - Finn Waagstein MD PhD: Finn Waagstein reflects on his work and research which saw
      beta-blockers revolutionise the treatment of heart failure patients. Mark
      Nicholls reports.

PMID- 29177414
TI  - European Heart Journal - Cardiovascular Pharmacotherapy: A fast growing baby
      filling an important gap in the literature.

PMID- 29177415
TI  - ESC CardioMed: The new ESC Textbook of Cardiovascular Medicine, an innovative
      digital textbook database for today's cardiologists from the European Society of
      Cardiology will soon be available.

PMID- 29177416
TI  - David Wood MD FRCP FESC: World Heart Federation (WHF) President Professor David
      Wood discusses the role, influence and impact of the organisation as it nears its
      40th anniversary.

PMID- 29177417
TI  - Ferrara I: Introduction: Why and how do cardiologists need to take an interest
      and lead prevention programmes?

PMID- 29177418
TI  - New Twitter Editor, European Society of Cardiology Journals.

PMID- 29177419
TI  - From 'essential' hypertension to intensive blood pressure lowering: the pros and
      cons of lower target values.

PMID- 29177420
TI  - Endothelin-1 may play an important role in the Fontan circulation.
AB  - OBJECTIVES: Our goal was to evaluate whether endothlin-1 (ET-1) plays an
      important role in the Fontan circulation. METHODS: Thirteen patients with single
      ventricle physiology (Glenn circulation, n = 7; Fontan circulation, n = 6) were
      evaluated using lung histopathological and immunohistochemical studies and then
      compared with the normal autopsied controls without congenital heart disease (n =
      13). We evaluated the medial thickness of the small pulmonary arteries. For 10 of
      these patients, quantitative real-time polymerase chain reaction analyses of ET
      1, endothelin receptors Type A and Type B, endothelin-converting enzyme-1 and
      endothelial nitric oxide synthase were performed. RESULTS: The medial thickness
      of the small pulmonary arteries in patients with single-ventricle physiology was
      greater than that of those in the control group (P = 0.0341). Severe medial
      hypertrophy of the pulmonary arteries was observed in patients who had poor
      outcomes. Immunohistochemical studies revealed that the marked expression of ET-1
      was observed in the endothelium and media of their pulmonary arteries. In these
      patients, the messenger RNA expression of ET-1 was also increased. Two patients
      showed high levels of expression of ETAR and ETBR, although these 2 cases
      maintain good Fontan circulation. CONCLUSIONS: Medial hypertrophy and the
      overexpression of ET-1 in the pulmonary arteries were observed in some patients
      in whom the Fontan circulation failed. Our data suggest that ET-1 may play an
      important role in maintaining the Fontan circulation.

PMID- 29177421
TI  - Endoperoxide-based compounds: cross-resistance with artemisinins and selection of
      a Plasmodium falciparum lineage with a K13 non-synonymous polymorphism.
AB  - Background: Owing to the emergence of multiresistant Plasmodium falciparum
      parasites in Southeast Asia, along with the impressive decrease in the efficacy
      of the endoperoxide compound artemisinin and of artemisinin-based combination
      therapies, the development of novel antimalarial drugs or combinations is
      required. Although several antiplasmodial molecules, such as endoperoxide-based
      compounds, are in advanced research or development, we do not know whether
      resistance to artemisinin derivatives might impact the efficacy of these new
      compounds. Objectives: To address this issue, the antiplasmodial efficacy of
      trioxaquines, hybrid endoperoxide-based molecules, was explored, along with their
      ability to select in vitro resistant parasites under discontinuous and dose
      escalating drug pressure. Methods: The in vitro susceptibilities of artemisinin-
      and trioxaquine-resistant laboratory strains and recent Cambodian field isolates
      were evaluated by different phenotypic and genotypic assays. Results:
      Trioxaquines tested presented strong cross-resistance with artemisinin both in
      the artemisinin-resistant laboratory F32-ART5 line and in Cambodian field
      isolates. Trioxaquine drug pressure over 4 years led to the in vitro selection of
      the F32-DU line, which is resistant to trioxaquine and artemisinin, similar to
      the F32-ART lineage. F32-DU whole genome sequencing (WGS) revealed that
      resistance to trioxaquine was associated with the same non-synonymous mutation in
      the propeller domain of the K13 protein (M476I) that was found in the F32-ART
      lineage. Conclusions: These worrisome results indicate the risk of cross
      resistance between artemisinins and endoperoxide-based antiplasmodial drugs in
      the development of the K13 mutant parasites and question the usefulness of these
      molecules in the future therapeutic arsenal.

PMID- 29177422
TI  - The TFIIE-related Rpc82 subunit of RNA polymerase III interacts with the TFIIB
      related transcription factor Brf1 and the polymerase cleft for transcription
      initiation.
AB  - Rpc82 is a TFIIE-related subunit of the eukaryotic RNA polymerase III (pol III)
      complex. Rpc82 contains four winged-helix (WH) domains and a C-terminal coiled
      coil domain. Structural resolution of the pol III complex indicated that Rpc82
      anchors on the clamp domain of the pol III cleft to interact with the duplex DNA
      downstream of the transcription bubble. However, whether Rpc82 interacts with a
      transcription factor is still not known. Here, we report that a structurally
      disordered insertion in the third WH domain of Rpc82 is important for cell growth
      and in vitro transcription activity. Site-specific photo-crosslinking analysis
      indicated that the WH3 insertion interacts with the TFIIB-related transcription
      factor Brf1 within the pre-initiation complex (PIC). Moreover, crosslinking and
      hydroxyl radical probing analyses revealed Rpc82 interactions with the upstream
      DNA and the protrusion and wall domains of the pol III cleft. Our genetic and
      biochemical analyses thus provide new molecular insights into the function of
      Rpc82 in pol III transcription.

PMID- 29177424
TI  - Lpx1p links glucose-induced calcium signaling and plasma membrane H+-ATPase
      activation in Saccharomyces cerevisiae cells.
AB  - In yeast, as in other eukaryotes, calcium plays an essential role in signaling
      transduction to regulate different processes. Many pieces of evidence suggest
      that glucose-induced activation of plasma membrane H+-ATPase, essential for yeast
      physiology, is related to calcium signaling. Until now, no protein that could be
      regulated by calcium in this context has been identified. Lpx1p, a serine
      protease that is also involved in the glucose-induced activation of the plasma
      membrane H+-ATPase, could be a candidate to respond to intracellular calcium
      signaling involved in this process. In this work, by using different approaches,
      we obtained many pieces of evidence suggesting that the requirement of calcium
      signaling for activation of the plasma membrane H+-ATPase is due to its
      requirement for activation of Lpx1p. According to the current model, activation
      of Lpx1p would cause hydrolysis of an acetylated tubulin that maintains the
      plasma membrane H+-ATPase in an inactive state. Therefore, after its activation,
      Lpx1p would hydrolyze the acetylated tubulin making the plasma membrane H+-ATPase
      accessible for phosphorylation by at least one protein kinase.

PMID- 29177423
TI  - Salicylic Acid and Jasmonic Acid Pathways are Activated in Spatially Different
      Domains Around the Infection Site During Effector-Triggered Immunity in
      Arabidopsis thaliana.
AB  - The innate immune response is, in the first place, elicited at the site of
      infection. Thus, the host response can be different among the infected cells and
      the cells surrounding them. Effector-triggered immunity (ETI), a form of innate
      immunity in plants, is triggered by specific recognition between pathogen
      effectors and their corresponding plant cytosolic immune receptors, resulting in
      rapid localized cell death known as hypersensitive response (HR). HR cell death
      is usually limited to a few cells at the infection site, and is surrounded by a
      few layers of cells massively expressing defense genes such as Pathogenesis
      Related Gene 1 (PR1). This virtually concentric pattern of the cellular responses
      in ETI is proposed to be regulated by a concentration gradient of salicylic acid
      (SA), a phytohormone accumulated around the infection site. Recent studies
      demonstrated that jasmonic acid (JA), another phytohormone known to be mutually
      antagonistic to SA in many cases, is also accumulated in and required for ETI,
      suggesting that ETI is a unique case. However, the molecular basis for this
      uniqueness remained largely to be solved. Here, we found that, using intravital
      time-lapse imaging, the JA signaling pathway is activated in the cells
      surrounding the central SA-active cells around the infection sites in Arabidopsis
      thaliana. This distinct spatial organization explains how these two phythormone
      pathways in a mutually antagonistic relationship can be activated simultaneously
      during ETI. Our results re-emphasize that the spatial consideration is a key
      strategy to gain mechanistic insights into the apparently complex signaling cross
      talk in immunity.

PMID- 29177425
TI  - Value of Neonicotinoid Insecticide Seed Treatments in Mid-South Corn (Zea mays)
      Production Systems.
AB  - Neonicotinoid seed treatments are one of several effective control options used
      in corn, Zea mays L., production in the Mid-South for early season insect pests.
      An analysis was performed on 91 insecticide seed treatment trials from Arkansas,
      Louisiana, Mississippi, and Tennessee to determine the value of neonicotinoids in
      corn production systems. The analysis compared neonicotinoid insecticide treated
      seed plus a fungicide to seed only with the same fungicide. When analyzed by
      state, corn yields were significantly higher when neonicotinoid seed treatments
      were used compared to fungicide only treated seed in Louisiana and Mississippi.
      Corn seed treated with neonicotinoid seed treatments yielded 111, 1,093, 416, and
      140 kg/ha, higher than fungicide only treatments for Arkansas, Louisiana,
      Mississippi, and Tennessee, respectively. Across all states, neonicotinoid seed
      treatments resulted in a 700 kg/ha advantage compared to fungicide only treated
      corn seed. Net returns for corn treated with neonicotinoid seed treatment were
      $1,446/ha compared with $1,390/ha for fungicide only treated corn seed across the
      Mid-South. Economic returns for neonicotinoid seed treated corn were
      significantly greater than fungicide-only-treated corn seed in 8 out of 14 yr.
      When analyzed by state, economic returns for neonicotinoid seed treatments were
      significantly greater than fungicide-only-treated seed in Louisiana. In some
      areas, dependent on year, neonicotinoid seed treatments provide significant yield
      and economic benefits in Mid-South corn.

PMID- 29177426
TI  - The Neutrons for Science Facility at SPIRAL-2.
AB  - The neutrons for science (NFS) facility is a component of SPIRAL-2, the new
      superconducting linear accelerator built at GANIL in Caen (France). The proton
      and deuteron beams delivered by the accelerator will allow producing intense
      neutron fields in the 100 keV-40 MeV energy range. Continuous and quasi-mono
      kinetic energy spectra, respectively, will be available at NFS, produced by the
      interaction of a deuteron beam on a thick Be converter and by the 7Li(p,n)
      reaction on thin converter. The pulsed neutron beam, with a flux up to two orders
      of magnitude higher than those of other existing time-of-flight facilities, will
      open new opportunities of experiments in fundamental research as well as in
      nuclear data measurements. In addition to the neutron beam, irradiation stations
      for neutron-, proton- and deuteron-induced reactions will be available for cross
      sections measurements and for the irradiation of electronic devices or biological
      cells. NFS, whose first experiment is foreseen in 2018, will be a very powerful
      tool for physics, fundamental research as well as applications like the
      transmutation of nuclear waste, design of future fission and fusion reactors,
      nuclear medicine or test and development of new detectors.

PMID- 29177428
TI  - Corrigendum: Low serum progesterone on the day of embryo transfer is associated
      with a diminished ongoing pregnancy rate in oocyte donation cycles after
      artificial endometrial preparation: a prospective study.

PMID- 29177429
TI  - Identification of a basidiomycete-specific Vilse-like GTPase activating proteins
      (GAPs) and its roles in the production of virulence factors in Cryptococcus
      neoformans.
AB  - Cryptococcus neoformans is a basidiomycetous pathogenic yeast that causes fatal
      infections in both immunocompetent and immunocompromised patients. Regulation on
      the production of its virulence factors is not fully understood. Here we reported
      the characterization of a gene, named CVH1(CNA06260), encoding a Drosophila Vilse
      like RhoGAP homolog, which is hallmarked by three conserved functional domains:
      WW, MyTH4 and RhoGAP. Phylogenetic analysis suggests that CVH1 is highly
      conserved from protists to mammals and interestingly in basidiomycetes, but
      absent in plants or Ascomycota and other lower fungi. This phylogenetic
      distribution indicates an evolutionary link among these groups of organisms.
      Functional analyses demonstrated that CVH1 was involved in stress tolerance and
      virulence factor production. By disrupting CVH1, we created a second mutant
      cvh1Delta with the CRISPR-Cas9 editing tool. The mutant strain exhibited
      hypersensitivity to osmotic stress by 2 M sorbitol and NaCl, suggesting defects
      in the HOG signaling pathway and an interaction of Cvh1 with the HOG pathway.
      Hypersensitivity of cvh1Delta to 1% Congo red and 0.01% SDS suggests that the
      cell wall integrity was impaired in the mutant. And cvh1Delta hardly produced the
      pigment melanin and capsule. Our study for the first time demonstrates that the
      fungal Vilse-like RhoGAP CVH1 is an important regulator of multiple biological
      processes in C. neoformans, and provides novel insights into the regulatory
      circuit of stress resistance/cell wall integrity, and laccase and capsule
      synthesis in C. neoformans.

PMID- 29177427
TI  - Synaptic phosphorylated alpha-synuclein in dementia with Lewy bodies.
AB  - Dementia with Lewy bodies is characterized by the accumulation of Lewy bodies and
      Lewy neurites in the CNS, both of which are composed mainly of aggregated alpha
      synuclein phosphorylated at Ser129. Although phosphorylated alpha-synuclein is
      believed to exert toxic effects at the synapse in dementia with Lewy bodies and
      other alpha-synucleinopathies, direct evidence for the precise synaptic
      localization has been difficult to achieve due to the lack of adequate optical
      microscopic resolution to study human synapses. In the present study we applied
      array tomography, a microscopy technique that combines ultrathin sectioning of
      tissue with immunofluorescence allowing precise identification of small
      structures, to quantitatively investigate the synaptic phosphorylated alpha
      synuclein pathology in dementia with Lewy bodies. We performed array tomography
      on human brain samples from five patients with dementia with Lewy bodies, five
      patients with Alzheimer's disease and five healthy control subjects to analyse
      the presence of phosphorylated alpha-synuclein immunoreactivity at the synapse
      and their relationship with synapse size. Main analyses were performed in blocks
      from cingulate cortex and confirmed in blocks from the striatum of cases with
      dementia with Lewy bodies. A total of 1 318 700 single pre- or postsynaptic
      terminals were analysed. We found that phosphorylated alpha-synuclein is present
      exclusively in dementia with Lewy bodies cases, where it can be identified in the
      form of Lewy bodies, Lewy neurites and small aggregates (<0.16 um3). Between 19%
      and 25% of phosphorylated alpha-synuclein deposits were found in presynaptic
      terminals mainly in the form of small aggregates. Synaptic terminals that co
      localized with small aggregates of phosphorylated alpha-synuclein were
      significantly larger than those that did not. Finally, a gradient of
      phosphorylated alpha-synuclein aggregation in synapses (pre > pre + post >
      postsynaptic) was observed. These results indicate that phosphorylated alpha
      synuclein is found at the presynaptic terminals of dementia with Lewy bodies
      cases mainly in the form of small phosphorylated alpha-synuclein aggregates that
      are associated with changes in synaptic morphology. Overall, our data support the
      notion that pathological phosphorylated alpha-synuclein may disrupt the structure
      and function of the synapse in dementia with Lewy bodies.

PMID- 29177430
TI  - Conformational heterogeneity and bubble dynamics in single bacterial
      transcription initiation complexes.
AB  - Transcription initiation is a major step in gene regulation for all organisms. In
      bacteria, the promoter DNA is first recognized by RNA polymerase (RNAP) to yield
      an initial closed complex. This complex subsequently undergoes conformational
      changes resulting in DNA strand separation to form a transcription bubble and an
      RNAP-promoter open complex; however, the series and sequence of conformational
      changes, and the factors that influence them are unclear. To address the
      conformational landscape and transitions in transcription initiation, we applied
      single-molecule Forster resonance energy transfer (smFRET) on immobilized
      Escherichia coli transcription open complexes. Our results revealed the existence
      of two stable states within RNAP-DNA complexes in which the promoter DNA appears
      to adopt closed and partially open conformations, and we observed large-scale
      transitions in which the transcription bubble fluctuated between open and closed
      states; these transitions, which occur roughly on the 0.1 s timescale, are
      distinct from the millisecond-timescale dynamics previously observed within
      diffusing open complexes. Mutational studies indicated that the sigma70 region
      3.2 of the RNAP significantly affected the bubble dynamics. Our results have
      implications for many steps of transcription initiation, and support a bend-load
      open model for the sequence of transitions leading to bubble opening during open
      complex formation.

PMID- 29177431
TI  - Significance of preoperative butyrylcholinesterase level as an independent
      predictor of survival in patients with upper urinary tract urothelial carcinoma
      treated with nephroureterectomy.
AB  - Objectives: Butyrylcholinesterase (BChE) is an alpha-glycoprotein synthesized in
      the liver. Its serum levels are reportedly correlated with disease activity in
      patients with cancer. The aim of this study was to estimate the potential
      prognostic significance of preoperative serum BChE levels in patients with upper
      urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy
      (RNU). Methods: Of the 220 patients with UTUC who underwent RNU between 1995 and
      2016 at Hirosaki University Hospital, 149 patients with available laboratory data
      were included for analysis. Covariates included age, sex, preoperative laboratory
      data, clinical T and N grades, tumor grade, tumor location and preoperative
      chemotherapy. Univariate and multivariate analyses were performed to identify
      clinical factors associated with overall survival (OS) and disease-free survival
      (DFS). Univariate analysis was performed using the Kaplan-Meier and log-rank
      methods, and the multivariate analysis was performed using a Cox proportional
      hazard model. Results: The median BChE level was 276 U/l and the optimal cut-off
      point for the serum BChE level was determined to be 218 IU/ml. The 5-year OS and
      DFS rates were 81.0% and 73.7%, respectively. The 5-year OS and DFS rates were
      significantly greater in the BChE >= 218 than <218 U/l groups (86.6% vs. 53.7%, P
      < 0.001 and 76.4% vs. 58.3%, P = 0.049, respectively). In multivariate analysis,
      BChE levels were most significantly associated with OS, whereas BChE level and
      tumor grade were significantly associated with DFS. Conclusions: This study
      validated preoperative serum BChE levels as an independent prognostic factor for
      UTUC after RNU.

PMID- 29177432
TI  - Diagnostic Nuclear Medicine for Paediatric Patients in Australia: Assessing the
      Individual's Dose Burden.
AB  - We report data for all Australians aged 0-19 y who underwent publicly funded
      nuclear medicine studies between 1985 and 2005, inclusive. Radiation doses were
      estimated for individual patients for 95 different types of studies. There were
      374 848 occasions of service for 277 511 patients with a collective effective
      dose of 1123 Sievert (Sv). Most services were either bone scans (45%) or renal
      scans (29%), with renal scans predominating at younger ages and bone scans at
      older ages. This pattern persisted despite a 4-fold increase in the annual number
      of procedures. Younger children were more likely to experience multiple scans,
      with the third quartile of scans per patient dropping from two to one with
      patient age. The median effective dose per patient ranged from 1.3 mSv (4-7 y
      old) to 2.8 mSv (13-16 y old). This large data set provides valuable information
      on nuclear medicine services for young Australians in the period 1985-2005.

PMID- 29177433
TI  - Erratum to: The One Health path to infectious disease prevention and resilience.

PMID- 29177434
TI  - A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy
      versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2
      polysomy or gene amplification.
AB  - Background: Approximately 5%-10% of gastric cancers have a fibroblast growth
      factor receptor-2 (FGFR2) gene amplification. AZD4547 is a selective FGFR-1, 2, 3
      tyrosine kinase inhibitor with potent preclinical activity in FGFR2 amplified
      gastric adenocarcinoma SNU16 and SGC083 xenograft models. The randomized phase II
      SHINE study (NCT01457846) investigated whether AZD4547 improves clinical outcome
      versus paclitaxel as second-line treatment in patients with advanced gastric
      adenocarcinoma displaying FGFR2 polysomy or gene amplification detected by
      fluorescence in situ hybridization. Patients and methods: Patients were
      randomized 3:2 (FGFR2 gene amplification) or 1:1 (FGFR2 polysomy) to AZD4547 or
      paclitaxel. Patients received AZD4547 80 mg twice daily, orally, on a 2 weeks
      on/1 week off schedule of a 21-day cycle or intravenous paclitaxel 80 mg/m2
      administered weekly on days 1, 8, and 15 of a 28-day cycle. The primary end point
      was progression-free survival (PFS). Safety outcomes were assessed and an
      exploratory biomarker analysis was undertaken. Results: Of 71 patients randomized
      (AZD4547 n = 41, paclitaxel n = 30), 67 received study treatment (AZD4547 n = 40,
      paclitaxel n = 27). Among all randomized patients, median PFS was 1.8 months with
      AZD4547 and 3.5 months with paclitaxel (one-sided P = 0.9581); median follow-up
      duration for PFS was 1.77 and 2.12 months, respectively. The incidence of adverse
      events was similar in both treatment arms. Exploratory biomarker analyses
      revealed marked intratumor heterogeneity of FGFR2 amplification and poor
      concordance between amplification/polysomy and FGFR2 mRNA expression.
      Conclusions: AZD4547 did not significantly improve PFS versus paclitaxel in
      gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor
      heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2
      amplification/polysomy and FGFR2 expression indicates the need for alternative
      predictive biomarker testing. AZD4547 was generally well tolerated.

PMID- 29177435
TI  - De novo mutations implicate novel genes in systemic lupus erythematosus.
AB  - The omnigenic model of complex disease stipulates that the majority of the
      heritability will be explained by the effects of common variation on genes in the
      periphery of core disease pathways. Rare variant associations, expected to
      explain far less of the heritability, may be enriched in core disease genes and
      thus will be instrumental in the understanding of complex disease pathogenesis
      and their potential therapeutic targets. Here, using complementary whole-exome
      sequencing, high-density imputation, and in vitro cellular assays, we identify
      candidate core genes in the pathogenesis of systemic lupus erythematosus (SLE).
      Using extreme-phenotype sampling, we sequenced the exomes of 30 SLE parent
      affected-offspring trios and identified 14 genes with missense de novo mutations
      (DNM), none of which are within the >80 SLE susceptibility loci implicated
      through genome-wide association studies. In a follow-up cohort of 10, 995
      individuals of matched European ancestry, we imputed genotype data to the density
      of the combined UK10K-1000 genomes Phase III reference panel across the 14
      candidate genes. Gene-level analyses indicate three functional candidates:
      DNMT3A, PRKCD, and C1QTNF4. We identify a burden of rare variants across PRKCD
      associated with SLE risk (P = 0.0028), and across DNMT3A associated with two
      severe disease prognosis sub-phenotypes (P = 0.0005 and P = 0.0033). We further
      characterise the TNF-dependent functions of the third candidate gene C1QTNF4 on
      NF-kappaB activation and apoptosis, which are inhibited by the p.His198Gln DNM.
      Our results identify three novel genes in SLE susceptibility and support extreme
      phenotype sampling and DNM gene discovery to aid the search for core disease
      genes implicated through rare variation.

PMID- 29177436
TI  - Designer tRNAs for efficient incorporation of non-canonical amino acids by the
      pyrrolysine system in mammalian cells.
AB  - The pyrrolysyl-tRNA synthetase/tRNAPyl pair is the most versatile and widespread
      system for the incorporation of non-canonical amino acids (ncAAs) into proteins
      in mammalian cells. However, low yields of ncAA incorporation severely limit its
      applicability to relevant biological targets. Here, we generate two tRNAPyl
      variants that significantly boost the performance of the pyrrolysine system.
      Compared to the original tRNAPyl, the engineered tRNAs feature a canonical hinge
      between D- and T-loop, show higher intracellular concentrations and bear
      partially distinct post-transcriptional modifications. Using the new tRNAs, we
      demonstrate efficient ncAA incorporation into a G-protein coupled receptor (GPCR)
      and simultaneous ncAA incorporation at two GPCR sites. Moreover, by incorporating
      last-generation ncAAs for bioorthogonal chemistry, we achieve GPCR labeling with
      small organic fluorophores on the live cell and visualize stimulus-induced GPCR
      internalization. Such a robust system for incorporation of single or multiple
      ncAAs will facilitate the application of a wide pool of chemical tools for
      structural and functional studies of challenging biological targets in live
      mammalian cells.

PMID- 29177437
TI  - Immunogenicity and Protection From a Single Dose of Internationally Available
      Killed Oral Cholera Vaccine: A Systematic Review and Metaanalysis.
AB  - In addition to improved water supply and sanitation, the 2-dose killed oral
      cholera vaccine (OCV) is an important tool for the prevention and control of
      cholera. We aimed to document the immunogenicity and protection (efficacy and
      effectiveness) conferred by a single OCV dose against cholera. The metaanalysis
      showed that an estimated 73% and 77% of individuals seroconverted to the Ogawa
      and Inaba serotypes, respectively, after an OCV first dose. The estimates of
      single-dose vaccine protection from available studies are 87% at 2 months
      decreasing to 33% at 2 years. Current immunologic and clinical data suggest that
      protection conferred by a single dose of killed OCV may be sufficient to reduce
      short-term risk in outbreaks or other high-risk settings, which may be especially
      useful when vaccine supply is limited. However, until more data suggest
      otherwise, a second dose should be given as soon as circumstances allow to ensure
      robust protection.

PMID- 29177438
TI  - Evaluating quality indicators of tertiary care hospitals for trauma care in
      Japan.
AB  - Objective: This study examined the associations between trauma mortality and
      quality of care indicators currently used in Japan. Design: This is a
      retrospective two-level discrete-time survival analysis. Quality indicators were
      derived from the 2012-2013 annual hospital survey conducted by the Ministry of
      Health, Labour and Welfare. Trauma mortality data were derived from the Japan
      Trauma Data Bank for the period of April 2012 to March 2013. Setting: Tertiary
      care centers designated as emergency and critical care centers (ECCCs) in Japan.
      Participants: The analysis included 12 378 patients aged >=15 years with blunt
      trauma and an Injury Severity Score >=9, registered to the data bank from 91
      ECCCs. Intervention: Quality of care indicators examined in the annual hospital
      survey. Main Outcome Measures: Deaths within 30 days. Results: Of the 12 378
      patients, 660 (5%) died within 30 days. Higher indicator score was significantly
      associated with lower mortality risk (hazard ratio [HR] for the second, third and
      fourth quartiles vs. lowest quartile 0.61, 0.55 and 0.52, respectively). Factors
      significantly associated with lower mortality risk were, higher patient volume
      (HR for the highest vs. lowest quartile, 0.74), director's qualification as
      specialist (HR 0.57) or consultant (HR 0.58), review of patient arrival process
      (HR 0.68), triage functions (HR 0.69), availability of psychiatrists (HR 0.75)
      and operating room being ready 24-h (HR 0.81). Conclusions: The study identified
      certain indicators associated with trauma patient mortality. Further refinement
      of indicators is required to specifically identify what needs changing.

PMID- 29177439
TI  - Attitudes, Beliefs, Practices, and Concerns Among Clinicians Prescribing Opioids
      in a Large Academic Institution.
AB  - Objectives: Opioid treatment of chronic noncancer pain (CNCP) adds complexity and
      uncertainty to patient interactions. We sought to assess clinician attitudes,
      beliefs, practice styles, and concerns around opioid prescribing following the
      release of the US Centers for Disease Control and Prevention (CDC) guideline for
      prescribing opioids for chronic pain. Methods: E-mailed electronic survey to
      clinicians at a large academic medical institution. Results: A total of 961
      clinicians responded to the survey (response rate = 40%), 720 of whom prescribed
      opioids and were not in training. Sixty-five percent were physicians, and 35%
      were nurse practitioners or physician assistants, with a mean age of 47 years (SD
      +/- 11.4 years). Eighty-two percent were reluctant to prescribe opioids for CNCP,
      and only 47% expressed confidence in their care for CNCP patients. Sixty-seven
      percent were aware of the CDC guideline, 55% were enrolled in the state
      Prescription Drug Monitoring Program (PDMP), and 2% always or frequently
      prescribed naloxone to patients on opioids. Guideline awareness was associated
      with increased confidence in caring for CNCP patients. Clinicians having
      knowledge of a patient overdose were 31% more likely to be enrolled in the PDMP
      (relative rate= 1.31, 95% confidence interval = 1.14-1.52, chi-square = 11.00, P
      <0.01). Clinicians who knew of a patient overdose event were also more likely to
      express concern about patient opioid dependence and addiction. Conclusions:
      Opportunities exist to increase awareness of the CDC guideline and to increase
      clinician confidence in opioid prescribing. Knowledge of an overdose event may
      influence clinician behavior and concerns about dependence and addiction.

PMID- 29177440
TI  - Patients' preferences for adjuvant sorafenib after resection of renal cell
      carcinoma in the SORCE trial: what makes it worthwhile?
AB  - Background: We sought to determine the survival benefits that patients judged
      sufficient to warrant adjuvant therapy with sorafenib for 1 year, or for 3 years
      after resection of renal cell carcinoma in the SORCE trial. Methods: SORCE
      participants from all sites in Australia and New Zealand, and selected sites in
      the UK, completed a validated preferences questionnaire at months 0, 3, 15, and
      42 to elicit the minimum survival benefits they judged sufficient to warrant
      adjuvant sorafenib for 1 year (versus observation), or for 3 years (versus 1
      year). The questionnaires used reference survival times of 5 and 15 years; and
      reference survival rates at 5 years of 65% and 85%. Results: The 233 participants
      had a median age of 57 years (range 29-78) and 71% were male. For 1 year of
      sorafenib versus no adjuvant therapy, the median benefits in survival times
      judged sufficient to warrant treatment were an extra 9 months beyond 5 years and
      an extra 1 year beyond 15 years; the median benefit in survival rates were an
      extra 4% beyond 65% and an extra 3% beyond 85% at 5 years. For 3 years of
      sorafenib versus 1 year of sorafenib, the median benefit in survival time judged
      sufficient to warrant extended treatment was an extra 1 year beyond both 5 and 15
      years. Participants randomly allocated to treatment with sorafenib judged larger
      benefits necessary than those allocated to placebo. Participants' preferences
      were not associated with their baseline characteristics or the interval from
      randomisation. Conclusion: Most participants judged an extra year of survival
      necessary to warrant 1 year of adjuvant sorafenib worthwhile, and an additional
      year of survival to warrant extending the duration of sorafenib from 1 to 3
      years. Patients' preferences are important in shared decision making. SORCE trial
      clinical trials number: NCT00492258.

PMID- 29177441
TI  - De novo mutations in Caudal Type Homeo Box transcription Factor 2 (CDX2) in
      patients with persistent cloaca.
AB  - The cloaca is an embryonic cavity that is divided into the urogenital sinus and
      rectum upon differentiation of the cloacal epithelium triggered by tissue
      specific transcription factors including CDX2. Defective differentiation leads to
      persistent cloaca in humans (PC), a phenotype recapitulated in Cdx2 mutant mice.
      PC is linked to hypo/hyper-vitaminosis A. Although no gene has ever been
      identified, there is a strong evidence for a genetic contribution to PC. We
      applied whole-exome sequencing and copy-number-variants analyses to 21 PC
      patients and their unaffected parents. The damaging p.Cys132* and p.Arg237His de
      novo CDX2 variants were identified in two patients. These variants altered the
      expression of CYP26A1, a direct CDX2 target encoding the major retinoic acid (RA)
      degrading enzyme. Other RA genes, including the RA-receptor alpha, were also
      mutated. Genes governing the development of cloaca-derived structures were
      recurrently mutated and over-represented in the basement-membrane components set
      (q-value < 1.65 * 10-6). Joint analysis of the patients' profile highlighted the
      extracellular matrix-receptor interaction pathway (MsigDBID: M7098, FDR: q-value
      < 7.16 * 10-9). This is the first evidence that PC is genetic, with genes
      involved in the RA metabolism at the lead. Given the CDX2 de novo variants and
      the role of RA, our observations could potentiate preventive measures. For the
      first time, a gene recapitulating PC in mouse models is found mutated in humans.

PMID- 29177442
TI  - Increased 27-hydroxycholesterol production during luteolysis may mediate the
      progressive decline in progesterone secretion.
AB  - STUDY QUESTION: Does 27-hydroxycholesterol (27OH) actively facilitate the
      progression of luteolysis? SUMMARY ANSWER: There is increased mRNA expression of
      the enzyme that produces 27OH during luteolysis in vivo in rhesus macaques and
      sheep, and 27OH reduces progesterone secretion from human luteinized granulosa
      cells. WHAT IS KNOWN ALREADY: There is an increase in mRNA expression of liver x
      receptor (LXR) and a decrease in sterol regulatory element binding protein 2
      (SREBP2) target genes during spontaneous luteolysis in primates, which could
      result in reduced cholesterol availability for steroidogenesis. Concentrations of
      27OH are also increased in primate corpora lutea (CL) during luteolysis, and 27OH
      is a dual LXR agonist and SREBP2 inhibitor. STUDY DESIGN SIZE, DURATION: This was
      an in vitro study using primary human luteinized granulosa cells in a control
      versus treatment(s) design. Analyses of CL from sheep undergoing induced or
      spontaneous luteolysis were also performed, along with database mining of
      microarray data from rhesus macaque CL. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Primary luteinizing granulosa cells were obtained from 37 women aged 24-44 who
      were undergoing oocyte donation or IVF for male factor or idiopathic infertility,
      and cells were further luteinized in vitro using human chorionic gonadotropin.
      Three approaches to test the effect of 27OH produced via CYP27A1 (cytochrome
      p450, family 27, subfamily A, polypeptide 1) on luteinized granulosa cells were
      used: (i) direct 27OH supplementation, (ii) induction of endogenous CYP27A1
      activity via pharmacologic inhibition of steroidogenesis, and (iii) siRNA
      mediated knockdown to directly inhibit CYP27A1 as well as cholesterol transport
      into the mitochondria via the steroidogenic acute regulatory protein (STAR).
      Endpoints included: progesterone (P4) secretion into culture media determined by
      enzyme immunoassay, cholesterol efflux and uptake assays using fluorescent lipid
      analogs, and mRNA expression determined via semi-quantitative real-time PCR
      (QPCR). An additional experiment involved QPCR analysis of 40 CL collected from
      ewes undergoing induced or spontaneous luteolysis, as well as database mining of
      microarray data generated from 16 rhesus macaque CL collected during spontaneous
      luteolysis and 13 macaque CL collected during a luteinizing hormone ablation and
      replacement protocol. MAIN RESULTS AND THE ROLE OF CHANCE: The mRNA expression of
      CYP27A1 was significantly increased during luteolysis in rhesus macaques and
      sheep in vivo, and CYP27A1 transcription was suppressed by luteinizing hormone
      and hCG. There was a significant decrease in hCG-stimulated P4 secretion from
      human luteinized granulosa cells caused by 27OH treatment, and a significant
      increase in basal and hCG-stimulated P4 synthesis when endogenous 27OH production
      was inhibited via CYP27A1 knockdown, indicating that 27OH inhibits
      steroidogenesis. Pharmacologic inhibition of steroidogenesis by aminoglutethimide
      significantly induced LXR and inhibited SREBP2 target gene mRNA expression,
      indicating that increased oxysterol production occurs when steroidogenesis is
      suppressed. Inhibiting cholesterol delivery into the mitochondria via knockdown
      of STAR resulted in reduced SREBP2 target gene mRNA expression, indicating that
      STAR function is necessary to maintain SREBP2-mediated transcription. The effects
      of 27OH treatment on markers of LXR and SREBP2 activity were moderate, and
      knockdown of CYP27A1 did not prevent aminoglutethimide-induced changes in LXR and
      SREBP2 target gene mRNA expression. These observations indicate that 27OH
      inhibits P4 secretion partially via mechanisms separate from its role as an LXR
      agonist and SREBP2 inhibitor, and also demonstrate that other oxysterols are
      involved in modulating LXR and SREBP2-mediated transcription when steroidogenesis
      is suppressed. LARGE SCALE DATA: None. LIMITATIONS REASONS FOR CAUTION:
      Luteinized granulosa cells may differ from luteal cells, and the effect on luteal
      function in vivo was not directly tested. The mechanisms that cause the initial
      rise in CYP27A1 mRNA expression during luteolysis are also not clear. WIDER
      IMPLICATIONS OF THE FINDINGS: The factors causing luteolysis in primates have not
      yet been determined. This study provides functional evidence of a novel mechanism
      via increased 27OH synthesis during luteolysis, which subsequently represses
      progesterone secretion. Increased 27OH may also facilitate the progression of
      luteolysis in domestic animal species. STUDY FUNDING AND COMPETING INTEREST(S):
      The authors have nothing to disclose. Support was provided by the Eunice Kennedy
      Shriver National Institute of Child Health & Human Development (NICHD) of the
      National Institutes of Health (NIH), award number R00HD067678 to R.L.B.

PMID- 29177443
TI  - Heterogeneous distribution of xylan and lignin in tension wood G-layers of the
      S1+G type in several Japanese hardwoods.
AB  - A gradual shift in the microfibril angle of gelatinous layer (G-layer) of tension
      wood fibres of the S1+G type has been detected via potassium permanganate (KMnO4)
      staining. Thus, microfibril angles in fibres of the S1+G type are different from
      S1+S2+G type fibres. We evaluated the microfibril orientation and presence of
      lignin and xylan in G-layers of tension wood fibres of the S1+G type in several
      Japanese hardwoods. The distribution of xylan and lignin was examined using
      immunoelectron microscopy with anti-xylan monoclonal antibody, ultraviolet (UV)
      microscopy, fluorescence microscopy after acrifravine staining and transmission
      electron microscopy after KMnO4 staining. In transverse sections, the outer parts
      of the G-layers showed ultraviolet absorption and a heterogeneous KMnO4 staining
      pattern, suggesting that lignin was heterogeneously distributed in the outer
      parts of the G-layers. The heterogeneous staining pattern was found in the G
      layers of several tree species; however, the degree of staining differed between
      tree species. In longitudinal sections, the KMnO4-staining region in the G-layers
      continued parallel to the cell axis to variable lengths. The orientation of
      cellulose microfibrils changed gradually from a steep helix to parallel to the
      cell axis from the outer to inner parts of the G-layers. Xylan immunolabelling
      was observed in the outer part of the G-layers; in some fibres, labelling was
      found in the innermost parts of the G-layers. Following immunogold labelling
      combined with KMnO4 staining, xylan labelling was mainly found in KMnO4-stained
      electron-opaque regions, suggesting that lignin and xylan were heterogeneously
      colocalized in the outer parts of the G-layers. The rotation of cellulose
      microfibrils and heterogeneous distribution of xylan and lignin might be a
      general phenomenon in S1+G tension wood fibres.

PMID- 29177444
TI  - Derivation of nearest-neighbor DNA parameters in magnesium from single molecule
      experiments.
AB  - DNA hybridization is an essential molecular reaction in biology with many
      applications. The nearest-neighbor (NN) model for nucleic acids predicts DNA
      thermodynamics using energy values for the different base pair motifs. These
      values have been derived from melting experiments in monovalent and divalent salt
      and applied to predict melting temperatures of oligos within a few degrees.
      However, an improved determination of the NN energy values and their salt
      dependencies in magnesium is still needed for current biotechnological
      applications seeking high selectivity in the hybridization of synthetic DNAs. We
      developed a methodology based on single molecule unzipping experiments to derive
      accurate NN energy values and initiation factors for DNA. A new set of values in
      magnesium is derived, which reproduces unzipping data and improves melting
      temperature predictions for all available oligo lengths, in a range of
      temperature and salt conditions where correlation effects between the magnesium
      bound ions are weak. The NN salt correction parameters are shown to correlate to
      the GC content of the NN motifs. Our study shows the power of single-molecule
      force spectroscopy assays to unravel novel features of nucleic acids such as
      sequence-dependent salt corrections.

PMID- 29177445
TI  - Do sleeping habits mediate the association between time spent on digital devices
      and school problems in adolescence?
AB  - Background: This study examined the associations of Internet and computer screen
      time with school difficulties and the role of sleep quality and soft and energy
      drinks consumption. Methods: We used data from the cross-sectional Health
      Behaviour in School-aged Children study collected in 2014 among Slovak
      adolescents (aged 11.0-15.9 years, N = 7595, 48.1% boys). We examined the inter
      relations between time spent with on digital devices (time spent playing digital
      games or Internet use), sleeping quality (sleeping shortage, sleeping
      difficulties), soft/energy drinks consumption and school problems (low academic
      achievement, disliking school, being pressured by schoolwork and truancy), using
      structural equation modeling. Results: Results showed that the more time
      adolescents spent on digital devices during leisure time, the more school
      problems they had. This association was mediated by a higher consumption of soft
      or energy drinks and a lower quality of sleeping. The direct effect of time spent
      on digital devices on school problems and its indirect effect via sleeping
      quality were relatively small (-0.26 and -0.30, respectively, standardized
      solution), compared with the indirect effect of time spent on digital devices via
      soft/energy drinks consumption as well as sleeping quality (0.65, standardized
      solution). Conclusions: Time spent on digital devices is associated with school
      problems, with sleeping and soft/energy drinks consumption playing a substantial
      role in this association.

PMID- 29177447
TI  - Oral glucan synthase inhibitor SCY-078 is effective in an experimental murine
      model of invasive candidiasis caused by WT and echinocandin-resistant Candida
      glabrata.
AB  - Background: Echinocandins are recommended as first-line therapy against Candida
      glabrata infections, although increased resistance to this class has been
      reported worldwide and they are currently only available for parenteral
      administration. SCY-078 is an investigational glucan synthase inhibitor that is
      orally available. Objectives: To evaluate the in vivo efficacy of SCY-078 in an
      experimental model of invasive candidiasis due to WT and echinocandin-resistant
      C. glabrata isolates. Methods: Neutropenic ICR mice were inoculated intravenously
      with a WT isolate (SCY-078 and caspofungin MICs 0.25 and 0.125 mg/L,
      respectively) or an echinocandin-resistant isolate (SCY-078 and caspofungin MICs
      1 and 0.5 mg/L, respectively). Treatment with placebo, SCY-078 (8, 30 or 40 mg/kg
      orally every 12 h) or caspofungin (1 mg/kg by intraperitoneal injection once
      daily) began 24 h later. Kidney fungal burden was measured on day 8 post
      inoculation. Results: Significant reductions in kidney fungal burden were
      observed with 30 mg/kg SCY-078 against both isolates and with the 40 mg/kg dose
      against the echinocandin-resistant isolate. These results were supported by SCY
      078 plasma concentration data at the higher doses, where levels above the MICs
      for both isolates were observed 12 h after the last oral dose. Reductions in
      fungal burden were also observed with caspofungin against the WT isolate, but not
      against the resistant isolate. Conclusions: SCY-078 demonstrated in vivo efficacy
      against infections caused by both WT and echinocandin-resistant C. glabrata
      isolates in this experimental model. This orally available glucan synthase
      inhibitor has potential as a therapy against echinocandin-resistant C. glabrata
      infections.

PMID- 29177448
TI  - Long-term results of annuloplasty in trivial-to-mild functional tricuspid
      regurgitation during mitral valve replacement: should we perform annuloplasty on
      the tricuspid valve or leave it alone?
AB  - OBJECTIVES: The benefits of concomitant tricuspid annuloplasty (TAP) for non
      significant functional tricuspid regurgitation (TR) during mitral valve
      replacement (MVR) are controversial. We evaluated the long-term outcomes
      particularly the long-term tricuspid valve (TV) functional outcomes-of MVR with
      or without tricuspid ring annuloplasty. METHODS: From 2004 to 2014, 256 patients
      (56.4 +/- 12.1 years) with trivial or mild functional TR who underwent MVR were
      enrolled. Eighty-two patients underwent concomitant tricuspid ring annuloplasty
      (TAP group), and 174 patients did not undergo the TV procedure (nTAP group).
      Propensity score-matched analysis was performed (n = 72 in each group). The
      follow-up duration was 77.4 +/- 42.4 months. RESULTS: The early clinical outcomes
      were similar between the 2 groups before and after propensity score matching with
      an early mortality rate of 3.5% (9 of 256). No patients experienced ring-related
      complications during follow-up. Eleven (6.3%) patients developed significant TR
      (>=moderate) in the nTAP group, while no patients developed significant TR in the
      TAP group. There were no significant differences in overall survival between the
      2 groups before or after matching. However, propensity score-matched analysis
      revealed that the freedom from significant TR aggravation and freedom from TV
      related event rates were significantly higher in the TAP group than in the nTAP
      group (P = 0.047 and P = 0.043, respectively). CONCLUSIONS: Patients with
      untreated trivial or mild functional TR accompanied by mitral valve disease can
      develop significant TR during follow-up. TV ring annuloplasty can be performed
      without complications and can be beneficial for patients with trivial or mild
      functional TR who are undergoing MVR.

PMID- 29177449
TI  - Efficacy of Ozone Against the Life Stages of Oryzaephilus mercator (Coleoptera:
      Silvanidae).
AB  - Ozone is a highly oxidizing gas with insecticidal activity and it is a potential
      alternative to conventional fumigants, such as phosphine and methyl bromide, for
      managing stored product insects. Susceptibility of the merchant grain beetle,
      Oryzaephilus mercator (Fauvel; Coleoptera: Silvanidae), an important pest of
      stored products, to ozone treatments is unknown. In this study, we investigated
      the efficacy of ozone for controlling O. mercator. We determined concentration
      mortality relationships for all stages of O. mercator exposed to 100-400 ppm for
      1 h (1 g/m3 = 467 ppm). We also determined time-mortality relationships for
      adults exposed to 100 ppm for 1-6 h. Mortality was recorded as percentages of
      eggs that failed to hatch 10 days after treatment (DAT), larvae or pupae that
      failed to develop into adults 20 or 15 DAT, respectively, and adults that died 2
      DAT. Generally, mortality increased with an increase in ozone concentration.
      Mortality was higher when insects were treated without food. When food was not
      provided, a minimum of 11030 ppm for 1 h is required to kill 99% of eggs, the
      most tolerant stage, whereas 500 ppm for 1 h is required to kill 99% of larvae,
      the least tolerant. When provided with food, adults were the most tolerant and
      larvae the least tolerant. Adults require exposure time of 7.7 h of 100 ppm ozone
      to kill 99% of insects in the absence of food. The work reported suggests that
      ozone could be an alternative fumigant for the management of all O. mercator life
      stages.

PMID- 29177446
TI  - A physiological perspective on the origin and evolution of photosynthesis.
AB  - The origin and early evolution of photosynthesis are reviewed from an
      ecophysiological perspective. Earth's first ecosystems were chemotrophic, fueled
      by geological H2 at hydrothermal vents and, required flavin-based electron
      bifurcation to reduce ferredoxin for CO2 fixation. Chlorophyll-based phototrophy
      (chlorophototrophy) allowed autotrophs to generate reduced ferredoxin without
      electron bifurcation, providing them access to reductants other than H2. Because
      high-intensity, short-wavelength electromagnetic radiation at Earth's surface
      would have been damaging for the first chlorophyll (Chl)-containing cells,
      photosynthesis probably arose at hydrothermal vents under low-intensity, long
      wavelength geothermal light. The first photochemically active pigments were
      possibly Zn-tetrapyrroles. We suggest that (i) after the evolution of red
      absorbing Chl-like pigments, the first light-driven electron transport chains
      reduced ferredoxin via a type-1 reaction center (RC) progenitor with electrons
      from H2S; (ii) photothioautotrophy, first with one RC and then with two, was the
      bridge between H2-dependent chemolithoautotrophy and water-splitting
      photosynthesis; (iii) photothiotrophy sustained primary production in the photic
      zone of Archean oceans; (iv) photosynthesis arose in an anoxygenic cyanobacterial
      progenitor; (v) Chl a is the ancestral Chl; and (vi), anoxygenic
      chlorophototrophic lineages characterized so far acquired, by horizontal gene
      transfer, RCs and Chl biosynthesis with or without autotrophy, from the
      architects of chlorophototrophy-the cyanobacterial lineage.

PMID- 29177451
TI  - Abstracts of the 16th Congress of European Society for Biomedical Research on
      Alcoholism (ESBRA) 8-11 October 2017 Heraklion, Greece.

PMID- 29177450
TI  - COMPARISON OF THE NEUTRON ENERGY RESPONSE OF TWO DIFFERENT TLD ALBEDO DOSEMETERS.
AB  - Albedo dosemeters remain the most used dosemeters in neutron individual
      monitoring. In Brazil, most of the neutron occupational fields are from
      radionuclide sources, often without any moderation, where albedo dosemeters have
      poor energy response. The purpose of this work is to compare the HP(10) energy
      response of the IRD and ALNOR TLD albedo dosemeter systems, calculated by their
      modelling with Monte Carlo code MCNPX. Their energy responses are similar, as
      expected, but the IRD system is about five times more sensitive than the ALNOR
      one. IRD albedo system can measure the Brazilian monthly recording level of 0.2
      mSv, even for bare 252Cf and 241Am-Be neutron fields. On the other hand, the
      ALNOR system can measure values higher than 0.2 mSv only after huge moderation of
      theses sources. These results show that IRD TLD albedo is more suitable than the
      ALNOR one to measure low doses at occupational fields from radionuclide sources.

PMID- 29177452
TI  - Effects of an internet-based educational intervention to prevent high-risk sexual
      behavior in Mexican adolescents.
AB  - : To evaluate the effect of an internet-based educational intervention to
      increase knowledge of sexually transmitted infections (STIs), attitudes and self
      efficacy toward consistent condom use in Mexican adolescents. A field trial with
      an intervention and control group was conducted in 14- to 15-year-old students in
      two secondary schools. The intervention was delivered via a website that included
      four educational sessions during a 4-week period and six 30-min class discussions
      during a 3-month period. In the control group, the investigators observed the
      general sex education provided by the school. Outcome variables were 1) knowledge
      about STIs, 2) attitudes regarding condom use, and 3) self-efficacy toward
      consistent condom use. Differences-in-differences (Diff-in-Diff) treatment effect
      was estimated for each outcome variable. There were 246 adolescents in the
      intervention group and 210 in the control group. The intervention had a positive
      effect on improving knowledge of STIs, attitudes and self-efficacy toward
      consistent condom use. The major effect was observed on adolescents' knowledge on
      STIs (Diff-in-Diff 30.34 points, P < 0.0001). A youth-friendly, culturally
      contextualized, internet-based educational intervention complemented by class
      discussions may be a significant addition to the regular secondary school sex
      education program to improve knowledge of STIs, attitudes and self-efficacy
      toward consistent condom use among adolescents. TRIAL REGISTRATION: The study was
      registered at the ClinicalTrials.gov ID: NCT02686736.

PMID- 29177453
TI  - Test-retest reliability of the adult ADHD Self-Report Scale (ASRS) v1.1 Screener
      in non-ADHD controls from a primary care physician practice.
AB  - Objectives: To examine the test-retest reliability of the DSM-IV Adult ADHD Self
      Report Scale (ASRS) v1.1 Screener in adults without ADHD. Prior studies have not
      examined test-retest reliability of the Screener in non-ADHD controls. Methods:
      Subjects completed the Screener in a primary care physician (PCP) waiting room
      (T1); those who screened negative for ADHD (n = 104) (<4/6 significant Screener
      items) symptoms were further assessed on the phone (T2). T2 included phone
      administration of the full ASRS v1.1 Symptom Checklist (which contains the six
      items from the Screener). Spearman's correlations and intra-class correlation
      coefficients (ICCs) between T1 and T2 were calculated for the total Screener
      score and for each Screener item. McNemar-Bowker tests were conducted for the
      Screener total score and each item to check for significant changes from T1 to
      T2. Results: Screener T1 and T2 total scores were significantly correlated
      (Spearman's rho = 0.78, P < 0.0001), as were individual items. Correlations
      remained significant when controlling for a variety of demographic factors and
      psychiatric conditions. Confirming the significant Spearman correlations, ICCs
      for Screener total score and each item were also significant (ICC = 0.75, P <
      0.0001). The McNemar-Bowker tests showed no significant differences for Screener
      total score and for the IA items; however, the H-I items were somewhat higher at
      T1 versus T2. Conclusions: The DSM-IV ASRS v1.1 Screener has high test-retest
      reliability in patients without ADHD.

PMID- 29177455
TI  - Investigating commercial in ovo technology as a strategy for introducing
      probiotic bacteria to broiler embryos.
AB  - Probiotics can improve broiler performance and reduce pathogens. Because the
      hatchery can be a source of contamination, delivering probiotics to the embryo
      before hatch is desirable. To date, probiotics have primarily been injected into
      eggs manually. Therefore, the objective of this study was to deliver various
      probiotic bacteria into broiler hatching eggs using an automated commercial in
      ovo injection system to evaluate hatchability of fertile eggs (HF). Three
      separate experiments were conducted using Lactobacillus acidophilus, Bacillus
      subtilis, or Bifidobacterium animalis. In each experiment, 7 treatments (non
      injected control; dry punch control; diluent-injected control; and injections of
      103 cfu, 104 cfu, 105 cfu, or 106 cfu of bacteria/50 MUL of diluent) were
      evaluated using 10 replicates per treatment. For each experiment, 2,490 eggs were
      obtained from a commercial hatchery. Eggs were incubated under standard
      incubation conditions. At 10 d of incubation (doi), eggs were candled, and
      infertile eggs were removed. On 18 doi, all eggs were injected with the
      appropriate treatment using an automated in ovo injection system. Once all eggs
      were injected, they were transferred to hatching baskets and placed into the
      hatcher. On 21 doi, chicks were removed from the hatcher, counted, and weighed.
      Hatch residue analysis was conducted to determine infertile, early dead, mid
      dead, late dead, pipped, cracked, contaminated, and cull chick statuses of all
      unhatched eggs. Injecting L. acidophilus, even at a concentration as high as 106
      cfu/50 MUL, did not impact hatch residue analysis (P > 0.05). However, HF was
      significantly less for eggs treated with B. subtilis than for control eggs (P <
      0.0001). For the non-injected control, HF was 91%, but as concentration of B.
      subtilis increased, HF decreased to as low as 1.67% for the 105 cfu treatment.
      Late deads, pipped, and contaminated egg percentages were higher, and chick BW
      was lower for B. subtilis treatment groups compared to controls. In conclusion,
      L. acidophilus and B. animalis but not B. subtilis, appear to be suitable
      candidates for in ovo injection as probiotics.

PMID- 29177456
TI  - Multiple Innovations in Genetic and Epigenetic Mechanisms Cooperate to Underpin
      Human Brain Evolution.
AB  - Our knowledge of how the human brain differs from those of other species in terms
      of evolutionary adaptations and functionality is limited. Comparative genomics
      reveal valuable insight, especially the expansion of human-specific noncoding
      regulatory and repeat-containing regions. Recent studies add to our knowledge of
      evolving brain function by investigating cellular mechanisms such as protein
      emergence, extensive sequence editing, retrotransposon activity, dynamic
      epigenetic modifications, and multiple noncoding RNA functions. These findings
      present an opportunity to combine newly discovered genetic and epigenetic
      mechanisms with more established concepts into a more comprehensive picture to
      better understand the uniquely evolved human brain.

PMID- 29177454
TI  - Factors influencing the activation of the rapid response system for clinically
      deteriorating patients by frontline ward clinicians: a systematic review.
AB  - Purpose: To synthesize factors influencing the activation of the rapid response
      system (RRS) and reasons for suboptimal RRS activation by ward nurses and junior
      physicians. Data sources: Nine electronic databases were searched for articles
      published between January 1995 and January 2016 in addition to a hand-search of
      reference lists and relevant journals. Study selection: Published primary studies
      conducted in adult general ward settings and involved the experiences and views
      of ward nurses and/or junior physicians in RRS activation were included. Data
      extraction: Data on design, methods and key findings were extracted and collated.
      Results of data synthesis: Thirty studies were included for the review. The
      process to RRS activation was influenced by the perceptions and clinical
      experiences of ward nurses and physicians, and facilitated by tools and
      technologies, including the sensitivity and specificity of the activation
      criteria, and monitoring technology. However, the task of enacting the RRS
      activations was challenged by seeking further justification, deliberating over
      reactions from the rapid response team and the impact of workload and staffing.
      Finally, adherence to the traditional model of escalation of care, support from
      colleagues and hospital leaders, and staff training were organizational factors
      that influence RRS activation. Conclusion: This review suggests that the factors
      influencing RRS activation originated from a combination of socio-cultural,
      organizational and technical aspects. Institutions that strive for improvements
      in the existing RRS or are considering to adopt the RRS should consider the
      complex interactions between people and the elements of technologies, tasks,
      environment and organization in healthcare settings.

PMID- 29177457
TI  - Assessing the capacity of social determinants of health data to augment
      predictive models identifying patients in need of wraparound social services.
AB  - Introduction: A growing variety of diverse data sources is emerging to better
      inform health care delivery and health outcomes. We sought to evaluate the
      capacity for clinical, socioeconomic, and public health data sources to predict
      the need for various social service referrals among patients at a safety-net
      hospital. Materials and Methods: We integrated patient clinical data and
      community-level data representing patients' social determinants of health (SDH)
      obtained from multiple sources to build random forest decision models to predict
      the need for any, mental health, dietitian, social work, or other SDH service
      referrals. To assess the impact of SDH on improving performance, we built
      separate decision models using clinical and SDH determinants and clinical data
      only. Results: Decision models predicting the need for any, mental health, and
      dietitian referrals yielded sensitivity, specificity, and accuracy measures
      ranging between 60% and 75%. Specificity and accuracy scores for social work and
      other SDH services ranged between 67% and 77%, while sensitivity scores were
      between 50% and 63%. Area under the receiver operating characteristic curve
      values for the decision models ranged between 70% and 78%. Models for predicting
      the need for any services reported positive predictive values between 65% and
      73%. Positive predictive values for predicting individual outcomes were below
      40%. Discussion: The need for various social service referrals can be predicted
      with considerable accuracy using a wide range of readily available clinical and
      community data that measure socioeconomic and public health conditions. While the
      use of SDH did not result in significant performance improvements, our approach
      represents a novel and important application of risk predictive modeling.

PMID- 29177458
TI  - A Survey of Physicians' Knowledge and Adherence to the Diagnostic Criteria for
      Fibromyalgia.
AB  - Objective: In 2010, Wolfe et al. demonstrated poor physician use of the 1990
      fibromyalgia diagnostic criteria and proposed the 2010 criteria to address
      physician shortcomings. No follow-up studies have investigated whether physicians
      are using these criteria. The purpose of this study was to provide seminal data
      on physician knowledge and use of the fibromyalgia diagnostic criteria. Methods:
      This was an observational study. A questionnaire was distributed to a convenience
      sample of physicians who diagnose chronic pain conditions. Physician agreement
      was evaluated with statements testing their knowledge on the fibromyalgia
      criteria, and then intraclass correlations were calculated to determine the
      homogeneity of physicians' responses. We also determined whether physician
      knowledge was impacted by their specialist training and clinical experience.
      Results: Physician responses varied between correct and incorrect agreement on
      most questions. Physician specialist training was positively correlated with
      knowledge of the criteria. Physician knowledge overall was not comprehensive and
      was very poor for the 1990 and 2010 criteria. Fifty-one percent of physicians
      used a set of criteria in their practice, and 49% used their clinical acumen.
      Conclusions: Physicians do not have adequate and homogenous knowledge of the
      fibromyalgia diagnostic criteria. Approximately half of physicians did not adhere
      to the criteria. Poor knowledge and adherence to the criteria may increase
      diagnosis delays and misdiagnoses. Knowledge translation strategies should be
      implemented to address this problem.

PMID- 29177459
TI  - Acclimation of branch and leaf hydraulics in adult Fagus sylvatica and Picea
      abies in a forest through-fall exclusion experiment.
AB  - Decreasing water availability due to climate change poses the question of whether
      and to what extent tree species are able to hydraulically acclimate and how
      hydraulic traits of stems and leaves are coordinated under drought. In a through
      fall exclusion experiment, hydraulic acclimation was analyzed in a mixed forest
      stand of Fagus sylvatica L. and Picea abies (L.) Karst. In drought-stressed (TE,
      through-fall exclusion over 2 years) and control (CO) trees, hydraulic
      vulnerability was studied in branches as well as in leaves (F. sylvatica) and end
      twigs (P. abies, entirely formed during the drought period) sampled at the same
      height in sun-exposed portions of the tree crown. In addition, relevant xylem
      anatomical traits and leaf pressure-volume relations were analyzed. The TE trees
      reached pre-dawn water potentials down to -1.6 MPa. In both species, water
      potentials at 50% loss of xylem hydraulic conductivity were ~0.4 MPa more
      negative in TE than in CO branches. Foliage hydraulic vulnerability (expressed as
      water potential at 50% loss of leaf/end-twig hydraulic conductance) and water
      potential at turgor loss point were also, respectively, 0.4 and 0.5 MPa lower in
      TE trees. Minor differences were observed in conduit mean hydraulic diameter and
      cell wall reinforcement. Our findings indicate significant and fast hydraulic
      acclimation under relatively mild drought in both tree species. Acclimation was
      well coordinated between branches and foliage, which might be essential for
      survival and productivity of mature trees under future drought periods.

PMID- 29177460
TI  - Characterization and evaluation of lactic acid bacteria candidates for intestinal
      epithelial permeability and Salmonella Typhimurium colonization in neonatal
      turkey poults.

PMID- 29177461
TI  - Rigorous Clinical Trial Design in Public Health Emergencies Is Essential.
AB  - Randomized clinical trials are the most reliable approaches to evaluating the
      effects of new treatments and vaccines. During the 2014-2015 West African Ebola
      epidemic, many argued that such trials were neither ethical nor feasible in an
      environment of limited health infrastructure and severe disease with a high
      fatality rate. Consensus among the numerous organizations providing help to the
      affected areas was never achieved, resulting in fragmented collaboration, delayed
      study initiation, and ultimately failure to provide definitive evidence on the
      efficacy of treatments and vaccines. Randomized trials were in fact approved by
      local ethics boards and initiated, demonstrating that randomized trials, even in
      such difficult circumstances, are feasible. Improved planning and collaboration
      among research and humanitarian organizations, and affected communities, in the
      interepidemic periods are needed to ensure that questions regarding the efficacy
      of vaccines and treatments can be definitively answered during future public
      health emergencies.

PMID- 29177463
TI  - Elevated potassium levels in patients with chronic kidney disease: occurrence,
      risk factors and clinical outcomes-a Danish population-based cohort study.
AB  - Background: Data on the true burden of hyperkalemia (HK) in patients with chronic
      kidney disease (CKD) in a real-world setting are scarce. Methods: The incidence
      rate of HK [first blood test with an elevated blood potassium level level >5.0
      mmol/L] in primary or hospital care was assessed in a population-based cohort of
      all newly diagnosed CKD patients [second estimated glomerular filtration rate
      (eGFR) measurement <60 mL/min/1.73 m 2 or hospital diagnosis] in northern
      Denmark. Risk factors and clinical outcomes were compared for CKD patients with
      HK and matched CKD patients without HK. Results: Of 157 766 patients with CKD,
      28% experienced HK, for an overall HK incidence rate of 70/1000 person-years.
      Among patients with Stage 3A, 3B, 4 or 5 CKD, 9, 18, 31 and 42%, respectively,
      experienced HK within the first year. Important HK risk factors included diabetes
      {prevalence ratio [PR] 1.74 [95% confidence interval (CI) 1.69-1.79]}, heart
      failure [PR 2.31 (95% CI 2.23-2.40)] and use of angiotensin-converting enzyme
      inhibitors [PR 1.45 (95% CI 1.42-1.48)], potassium supplements [PR 1.59 (95% CI
      1.55-1.62)] or spironolactone [PR 2.53 (95% CI 2.44-2.63)]. In CKD patients who
      developed HK, 34% had any acute hospitalization 6 months before the HK event,
      increasing to 57% 6 months after HK [before-after risk ratio 1.72 (95% CI 1.69
      1.74)]. The 6-month mortality following HK was 26%, versus 6% in matched non-HK
      patients. Compared with non-HK patients, 6-month hazard ratios for any acute
      hospitalization in HK patients were 2.11-fold higher, including hazard ratios of
      2.07 for cardiac diagnoses, 2.29 for ventricular arrhythmias, 3.26 for cardiac
      arrest, 4.77 for intensive care and 4.85 for death. Conclusions: More than one in
      four CKD patients develops HK. Patients with severe CKD, diabetes, heart failure
      or use of spironolactone are at high risk. HK is associated with severe clinical
      outcomes.

PMID- 29177464
TI  - QVZ: lossy compression of quality values.

PMID- 29177462
TI  - Cohort Profile: The NSPN 2400 Cohort: a developmental sample supporting the
      Wellcome Trust NeuroScience in Psychiatry Network.

PMID- 29177465
TI  - Aminoglycoside-mediated promotion of translation readthrough occurs through a non
      stochastic mechanism that competes with translation termination.
AB  - Attempts have been made to treat nonsense-associated genetic disorders by
      chemical agents and hence an improved mechanistic insight into the decoding of
      readthrough signals is essential for the identification and characterisation of
      factors for the treatment of these disorders. To identify either novel compounds
      or genes that modulate translation readthrough, we have employed dual reporter
      based high-throughput screens that use enzymatic and fluorescence activities and
      screened bioactive National Institute of Neurological Disease Syndrome (NINDS)
      compounds (n = 1000) and siRNA (n = 288) libraries. Whilst siRNAs targeting
      kinases such as CSNK1G3 and NME3 negatively regulate readthrough, neither the
      bioactive NINDS compounds nor PTC124 promote readthrough. Of note, PTC124 has
      previously been shown to promote readthrough. Furthermore, the impacts of G418 on
      the components of eukaryotic selenocysteine incorporation machinery have also
      been investigated. The selenocysteine machinery decodes the stop codon UGA
      specifying selenocysteine in natural selenoprotein genes. We have found that the
      eukaryotic SelC gene promotes the selenocysteine insertion sequence (SECIS)
      mediated readthrough but inhibits the readthrough activity induced by G418. We
      have previously reported that SECIS-mediated readthrough at UGA codons follows a
      non-processive mechanism. Here, we show that G418-mediated promotion of
      readthrough also occurs through a non-processive mechanism which competes with
      translation termination. Based on our observations, we suggest that proteins
      generated through a non-processive mechanism may be therapeutically beneficial
      for the resolution of nonsense-associated genetic disorders.

PMID- 29177467
TI  - True Pathogen or Contamination: Validation of Blood Cultures for the Diagnosis of
      Nosocomial Infections in a Developing Country.
AB  - Background: Blood culture results are frequently used to guide antibiotic
      decision-making, but culture contaminants need to be distinguished from true
      pathogens. Aims: To assess the contamination rate of blood cultures and validate
      a method to distinguish between true bacteraemia and contamination. Methods: We
      analysed blood culture results from children who were admitted to the paediatric
      ICU and paediatric wards at the Sardjito Hospital, Yogyakarta, Indonesia between
      December 2010 and February 2013. For each positive culture result, the type of
      isolated organism, time to positivity, and the number of positive culture sites
      were considered to classify the isolate as representing a true bacteraemia or
      contaminant. Results: There were 1293 cultures obtained from blood and 308
      (23.8%) were positive for bacterial growth. Fifty-three (4.1%) of the total
      cultures drawn fulfilled criteria for contaminants. The most common blood culture
      contaminants were coagulase-negative staphylococci. Conclusion: Using
      standardized criteria, it is possible to implement a working method to identify
      true nosocomial infection from blood culture contaminant, and thus limit the
      effect of contaminated blood culture on irrational antibiotic use.

PMID- 29177466
TI  - Modeling RNA secondary structure folding ensembles using SHAPE mapping data.
AB  - RNA secondary structure prediction is widely used for developing hypotheses about
      the structures of RNA sequences, and structure can provide insight about RNA
      function. The accuracy of structure prediction is known to be improved using
      experimental mapping data that provide information about the pairing status of
      single nucleotides, and these data can now be acquired for whole transcriptomes
      using high-throughput sequencing. Prior methods for using these experimental data
      focused on predicting structures for sequences assuming that they populate a
      single structure. Most RNAs populate multiple structures, however, where the
      ensemble of strands populates structures with different sets of canonical base
      pairs. The focus on modeling single structures has been a bottleneck for
      accurately modeling RNA structure. In this work, we introduce Rsample, an
      algorithm for using experimental data to predict more than one RNA structure for
      sequences that populate multiple structures at equilibrium. We demonstrate, using
      SHAPE mapping data, that we can accurately model RNA sequences that populate
      multiple structures, including the relative probabilities of those structures.
      This program is freely available as part of the RNAstructure software package.

PMID- 29177469
TI  - Erratum.

PMID- 29177468
TI  - Understanding the impact of accreditation on quality in healthcare: A grounded
      theory approach.

PMID- 29177470
TI  - Impaired cognition is associated with adverse outcome in older patients in the
      Emergency Department; the Acutely Presenting Older Patients (APOP) study.
AB  - Objective: to investigate whether cognitive impairment, measured early after
      Emergency Department (ED) arrival and irrespective of its cause, is independently
      associated with functional decline or mortality after 3 and 12 months in older ED
      patients. Design and setting: a prospective multi-centre cohort study in all
      Acutely Presenting Older Patients visiting the Emergency Department (APOP study)
      of three hospitals in the Netherlands. Participants: 2,130 patients, >=70 years.
      Measurements: data on demographics, disease severity and geriatric
      characteristics were collected during the first hour of the ED visit. Cognition
      was measured using the 6-Item-Cognitive-Impairment-Test ('6CIT'). Cognitive
      impairment was defined as 6CIT >=11, self-reported dementia or the inability to
      perform the cognition test. The composite adverse outcome after 3 and 12 months
      was defined as a 1-point decrease in Katz Activities of Daily Living (ADL), new
      institutionalisation or mortality. Multivariable regression analysis was used to
      assess whether cognitive impairment independently associates with adverse
      outcome. Results: of 2,130 included patients, 588 (27.6%) had cognitive
      impairment at baseline and 654 patients (30.7%) suffered from adverse outcome
      after 3 months. Cognitive impairment associated with increased risk for adverse
      outcome (adjusted odds ratio (OR) 1.72, 95%CI 1.37-2.17). After 12 months, 787
      patients (36.9%) suffered from adverse outcome. Again, cognitive impairment
      independently associated with increased risk for adverse outcome (adjusted OR
      1.89, 95%CI 1.46-2.46). ORs were similar for patients who were discharged home
      versus hospitalised patients. Conclusion: cognitive impairment measured during
      the early stages of ED visit, irrespective of the cause, is independently
      associated with adverse outcome after 3 and 12 months in older patients.

PMID- 29177471
TI  - Long-Term Improvement in Aortic Pulse Wave Velocity After Weight Loss Can Be
      Predicted by White Adipose Tissue Factors.
AB  - BACKGROUND: Arterial stiffness, measured by pulse wave velocity (PWV), is linked
      to obesity, cardiovascular disease, and all-cause mortality. Short-term weight
      loss improves PWV, but the long-term effects are unknown. We investigated the
      effect of pronounced long-term weight loss on PWV and whether
      anthropometric/metabolic parameters and/or white adipose tissue (WAT) phenotype
      could predict this change in PWV. METHODS: Eighty-two obese subjects were
      examined before and 2 years after Roux-en-Y gastric bypass. Analyses included
      anthropometrics, routine clinical chemistry, and hyperinsulinemic-euglycemic
      clamp. Arterial stiffness was measured as aortic PWV (aPWV) using the
      Arteriograph device. WAT mass and distribution were assessed by dual-X-ray
      absorptiometry. Baseline visceral and subcutaneous WAT samples were obtained to
      measure adipocyte cell size. Transcriptomic profiling of subcutaneous WAT was
      performed in a subset of subjects (n = 30). RESULTS: At the 2-year follow-up,
      there were significant decreases in body mass index (39.4 +/- 3.5 kg/m2 vs. 26.6
      +/- 3.4 kg/m2; P < 0.0001) and aPWV (7.8 +/- 1.5 m/s vs. 7.2 +/- 1.4 m/s; P =
      0.006). Multiple regression analyses showed that baseline subcutaneous adipocyte
      volume was associated with a reduction in aPWV (P = 0.014), after adjusting for
      confounders. Expression analyses of 52 genes implicated in arterial stiffness
      showed that only one, COL4A1, independently predicted improvements in aPWV after
      adjusting for confounders (P = 0.006). CONCLUSIONS: Bariatric surgery leads to
      long-term reduction in aPWV. This improvement can be independently predicted by
      subcutaneous adipocyte volume and WAT COL4A1 expression, which suggests that
      subcutaneous WAT has a role in regulating aPWV. CLINICAL TRIALS REGISTRATION:
      Trial Number NCT01727245 (clinicaltrials.gov).

PMID- 29177472
TI  - Response.

PMID- 29177473
TI  - Skeletal Muscle Interleukin-6 Regulates Hepatic Cytochrome P450 Expression:
      Effects of 16-Week High-Fat Diet and Exercise.
AB  - High-fat diet (HFD) induces several changes to the pathways regulating energy
      homeostasis and changes the expression of the hepatic cytochrome p450 (Cyp)
      enzyme-system. Despite these pervious findings, it is still unclear how the
      effects of HFD and especially HFD in combination with treadmill running affect
      hepatic Cyp expression. In this study, we investigated the mRNA and protein
      expression of selected Cyp's in mice subjected to 16 weeks of HFD and treadmill
      running. To understand the regulatory mechanisms behind the exercise-induced
      reversion of the HFD-induced changes in Cyp expression, we used a model in which
      the exercise-induced myokine and known regulator of hepatic Cyp's, interleukin-6
      (IL-6), were knocked out specifically in skeletal muscle. We found that HFD
      increased the mRNA expression of Cyp1a1 and Cyp4a10, and decreased the expression
      of Cyp2a4, Cyp2b10, Cyp2e1, and Cyp3a11. HFD in combination with treadmill
      running reversed the HFD increase in Cyp4a10 mRNA expression. In addition, we
      observed increased Cyp1a and Cyp3a protein expression as an effect of exercise,
      whereas Cyp2b expression was lowered as an effect of HFD. IL-6 effected the
      response in Cyp3a11 and Cyp1a expression. We observed no changes in the content
      of the aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X
      receptor, or peroxisome proliferation activator receptor alpha. In conclusion, we
      show that both HFD and exercise in HFD-fed animals can regulate hepatic Cyp
      expression and that changes in Cyp3a in response to HFD and exercise are
      dependent on skeletal muscular IL-6.

PMID- 29177474
TI  - Evaluating Fast Maximum Likelihood-Based Phylogenetic Programs Using Empirical
      Phylogenomic Data Sets.
AB  - The sizes of the data matrices assembled to resolve branches of the tree of life
      have increased dramatically, motivating the development of programs for fast, yet
      accurate, inference. For example, several different fast programs have been
      developed in the very popular maximum likelihood framework, including
      RAxML/ExaML, PhyML, IQ-TREE, and FastTree. Although these programs are widely
      used, a systematic evaluation and comparison of their performance using empirical
      genome-scale data matrices has so far been lacking. To address this question, we
      evaluated these four programs on 19 empirical phylogenomic data sets with
      hundreds to thousands of genes and up to 200 taxa with respect to likelihood
      maximization, tree topology, and computational speed. For single-gene tree
      inference, we found that the more exhaustive and slower strategies (ten searches
      per alignment) outperformed faster strategies (one tree search per alignment)
      using RAxML, PhyML, or IQ-TREE. Interestingly, single-gene trees inferred by the
      three programs yielded comparable coalescent-based species tree estimations. For
      concatenation-based species tree inference, IQ-TREE consistently achieved the
      best-observed likelihoods for all data sets, and RAxML/ExaML was a close second.
      In contrast, PhyML often failed to complete concatenation-based analyses, whereas
      FastTree was the fastest but generated lower likelihood values and more
      dissimilar tree topologies in both types of analyses. Finally, data matrix
      properties, such as the number of taxa and the strength of phylogenetic signal,
      sometimes substantially influenced the programs' relative performance. Our
      results provide real-world gene and species tree phylogenetic inference
      benchmarks to inform the design and execution of large-scale phylogenomic data
      analyses.

PMID- 29177475
TI  - Individually tailored vs. standardized substrate modification during
      radiofrequency catheter ablation for atrial fibrillation: a randomized study.
AB  - Aims: This randomized single-centre study sought to compare the efficacy and
      safety of pulmonary vein isolation (PVI) plus voltage-guided ablation vs. PVI
      with or without linear ablation depending on the type of atrial fibrillation
      (AF). Methods and results: Overall, 124 ablation-naive patients with paroxysmal
      or persistent AF were randomized to PVI with (persistent AF) or without
      (paroxysmal AF) additional linear ablation (control group) vs. PVI plus ablation
      of low-voltage areas (LVAs) irrespective of AF type. Bipolar voltage mapping was
      performed during stable sinus rhythm. An LVA consisted of  >= 3 adjacent mapping
      points that each had a peak-to-peak amplitude <=0.5 mV. After a mean follow-up of
      12 +/- 3 months, significantly more patients in the LVA ablation group were free
      from atrial arrhythmia recurrence >30 s off antiarrhythmic drugs (AADs) after a
      single procedure (primary endpoint) compared with control group patients [40/59
      (68%) vs. 25/59 (42%), log-rank P = 0.003]. Arrhythmia-free survival on or off
      AADs was found in 33/59 control group patients (56%) and in 41/59 LVA ablation
      group patients (70%) (adjusted log-rank P = 0.10). During the 7 day Holter
      monitoring period at 12 months, significantly more patients in the LVA ablation
      group were free from arrhythmia recurrence on or off AADs [45/50 (90%) vs. 33/46
      (72%), P = 0.04]. No between-group differences were observed regarding procedure
      duration, fluoroscopy time, and major complications. Conclusion: In this single
      centre study, individually tailored substrate modification guided by voltage
      mapping was associated with a significantly higher arrhythmia-free survival rate
      compared with a conventional approach applying linear ablation according to AF
      type.

PMID- 29177476
TI  - Functional relationships between wood structure and vulnerability to xylem
      cavitation in races of Eucalyptus globulus differing in wood density.
AB  - Wood density can be considered as a measure of the internal wood structure, and
      it is usually used as a proxy measure of other mechanical and functional traits.
      Eucalyptus is one of the most important commercial forestry genera worldwide, but
      the relationship between wood density and vulnerability to cavitation in this
      genus has been little studied. The analysis is hampered by, among other things,
      its anatomical complexity, so it becomes necessary to address more complex
      techniques and analyses to elucidate the way in which the different anatomical
      elements are functionally integrated. In this study, vulnerability to cavitation
      in two races of Eucalyptus globulus Labill. with different wood density was
      evaluated through Path analysis, a multivariate method that allows evaluation of
      descriptive models of causal relationship between variables. A model relating
      anatomical variables with wood properties and functional parameters was proposed
      and tested. We found significant differences in wood basic density and
      vulnerability to cavitation between races. The main exogenous variables
      predicting vulnerability to cavitation were vessel hydraulic diameter and fibre
      wall fraction. Fibre wall fraction showed a direct impact on wood basic density
      and the slope of vulnerability curve, and an indirect and negative effect over
      the pressure imposing 50% of conductivity loss (P50) through them. Hydraulic
      diameter showed a direct negative effect on P50, but an indirect and positive
      influence over this variable through wood density on one hand, and through
      maximum hydraulic conductivity (ks max) and slope on the other. Our results
      highlight the complexity of the relationship between xylem efficiency and safety
      in species with solitary vessels such as Eucalyptus spp., with no evident
      compromise at the intraspecific level.

PMID- 29177477
TI  - Impact of antimicrobial stewardship interventions on Clostridium difficile
      infection and clinical outcomes: segmented regression analyses.
AB  - Background: Antimicrobial exposure is associated with increased risk of
      Clostridium difficile infection (CDI), but the impact of prescribing
      interventions on CDI and other outcomes is less clear. Objectives: To evaluate
      the effect of an antimicrobial stewardship intervention targeting high-risk
      antimicrobials (HRA), implemented in October 2008, and to compare the findings
      with similar studies from a systematic review. Methods: All patients admitted to
      Medicine and Surgery in Ninewells Hospital from October 2006 to September 2010
      were included. Intervention effects on HRA use (dispensed DDD), CDI cases and
      mortality rates, per 1000 admissions per month, were analysed separately in
      Medicine and Surgery using segmented regression of interrupted time series (ITS)
      data. Data from comparable published studies were reanalysed using the same
      method. Results: Six months post-intervention, there were relative reductions in
      HRA use of 33% (95% CI 11-56) in Medicine and 32% (95% CI 19-46) in Surgery. At
      12 months, there was an estimated reduction in CDI of 7.0 cases/1000 admissions
      [relative change -24% (95% CI - 55 to 6)] in Medicine, but no change in Surgery
      {estimated 0.1 fewer cases/1000 admissions [-2% (95% CI - 116 to 112)]}.
      Mortality reduced throughout the study period, unaffected by the intervention. In
      all six comparable studies, HRA use reduced significantly, but reductions in CDI
      rates were only statistically significant in two and none measured mortality. Pre
      intervention CDI rates and trends influenced the intervention effect.
      Conclusions: Despite large reductions in HRA prescribing and reductions in CDI,
      demonstrating real-world impact of stewardship interventions remains challenging.

PMID- 29177478
TI  - Manipulation of Bryophyte Hosts by Pathogenic and Symbiotic Microbes.
AB  - The colonization of plant tissues by pathogenic and symbiotic microbes is
      associated with a strong and directed effort to reprogram host cells in order to
      permit, promote and sustain microbial growth. In response to colonization, hosts
      accommodate or sequester invading microbes by activating a set of complex
      regulatory programs that initiate symbioses or bolster defenses. Extensive
      research has elucidated a suite of molecular and physiological responses
      occurring in plant hosts and their microbial partners; however, this information
      is mostly limited to model systems representing evolutionarily young plant
      lineages such as angiosperms. The extent to which these processes are conserved
      across land plants is therefore poorly understood. In this review, we outline key
      aspects of host reprogramming that occur during plant-microbe interactions in
      early diverging land plants belonging to the bryophytes (liverworts, hornworts
      and mosses). We discuss how further knowledge of bryophyte-microbe interactions
      will advance our understanding of how plants and microbes co-operated and clashed
      during the conquest of land.

PMID- 29177479
TI  - Horizontal Acquisition and Transcriptional Integration of Novel Genes in Mosquito
      Associated Spiroplasma.
AB  - Genetic differentiation among symbiotic bacteria is important in shaping
      biodiversity. The genus Spiroplasma contains species occupying diverse niches and
      is a model system for symbiont evolution. Previous studies have established that
      two mosquito-associated species have diverged extensively in their carbohydrate
      metabolism genes despite having a close phylogenetic relationship. Notably,
      although the commensal Spiroplasma diminutum lacks identifiable pathogenicity
      factors, the pathogenic Spiroplasma taiwanense was found to have acquired a
      virulence factor glpO and its associated genes through horizontal transfer.
      However, it is unclear if these acquired genes have been integrated into the
      regulatory network. In this study, we inferred the gene content evolution in
      these bacteria, as well as examined their transcriptomes in response to glucose
      availability. The results indicated that both species have many more gene
      acquisitions from the Mycoides-Entomoplasmataceae clade, which contains several
      important pathogens of ruminants, than previously thought. Moreover, several
      acquired genes have higher expression levels than the vertically inherited
      homologs, indicating possible functional replacement. Finally, the virulence
      factor and its functionally linked genes in S. taiwanense were up-regulated in
      response to glucose starvation, suggesting that these acquired genes are under
      expression regulation and the pathogenicity may be a stress response. In summary,
      although differential gene losses are a major process for symbiont divergence,
      gene gains are critical in counteracting genome degradation and driving
      diversification among facultative symbionts.

PMID- 29177481
TI  - CDYL1 fosters double-strand break-induced transcription silencing and promotes
      homology-directed repair.
AB  - Cells have evolved DNA damage response (DDR) to repair DNA lesions and thus
      preserving genomic stability and impeding carcinogenesis. DNA damage induction is
      accompanied by transient transcription repression. Here, we describe a previously
      unrecognized role of chromodomain Y-like (CDYL1) protein in fortifying double
      strand break (DSB)-induced transcription repression and repair. We showed that
      CDYL1 is rapidly recruited to damaged euchromatic regions in a poly (ADP-ribose)
      polymerase 1 (PARP1)-dependent, but ataxia telangiectasia mutated (ATM)
      independent, manner. While the C-terminal region, containing the enoyl-CoA
      hydratase like (ECH) domain, of CDYL1 binds to poly (ADP-ribose) (PAR) moieties
      and mediates CDYL1 accumulation at DNA damage sites, the chromodomain and histone
      H3 trimethylated on lysine 9 (H3K9me3) mark are dispensable for its recruitment.
      Furthermore, CDYL1 promotes the recruitment of enhancer of zeste homolog 2
      (EZH2), stimulates local increase of the repressive methyl mark H3K27me3, and
      promotes transcription silencing at DSB sites. In addition, following DNA damage
      induction, CDYL1 depletion causes persistent G2/M arrest and alters H2AX and
      replication protein A (RPA2) phosphorylation. Remarkably, the 'traffic-light
      reporter' system revealed that CDYL1 mainly promotes homology-directed repair
      (HDR) of DSBs in vivo. Consequently, CDYL1-knockout cells display synthetic
      lethality with the chemotherapeutic agent, cisplatin. Altogether, our findings
      identify CDYL1 as a new component of the DDR and suggest that the HDR-defective
      'BRCAness' phenotype of CDYL1-deficient cells could be exploited for eradicating
      cancer cells harboring CDYL1 mutations.

PMID- 29177480
TI  - Comparative Genomic Analysis of Acanthamoeba Endosymbionts Highlights the Role of
      Amoebae as a "Melting Pot" Shaping the Rickettsiales Evolution.
AB  - Amoebae have been considered as a genetic "melting pot" for its symbionts,
      facilitating genetic exchanges of the bacteria that co-inhabit the same host. To
      test the "melting pot" hypothesis, we analyzed six genomes of amoeba
      endosymbionts within Rickettsiales, four of which belong to Holosporaceae family
      and two to Candidatus Midichloriaceae. For the first time, we identified plasmids
      in obligate amoeba endosymbionts, which suggests conjugation as a potential
      mechanism for lateral gene transfers (LGTs) that underpin the "melting pot"
      hypothesis. We found strong evidence of recent LGTs between the Rickettsiales
      amoeba endosymbionts, suggesting that the LGTs are continuous and ongoing. In
      addition, comparative genomic and phylogenomic analyses revealed pervasive and
      recurrent LGTs between Rickettsiales and distantly related amoeba-associated
      bacteria throughout the Rickettsiales evolution. Many of these exchanged genes
      are important for amoeba-symbiont interactions, including genes in transport
      system, antibiotic resistance, stress response, and bacterial virulence,
      suggesting that LGTs have played important roles in the adaptation of
      endosymbionts to their intracellular habitats. Surprisingly, we found little
      evidence of LGTs between amoebae and their bacterial endosymbionts. Our study
      strongly supports the "melting pot" hypothesis and highlights the role of amoebae
      in shaping the Rickettsiales evolution.

PMID- 29177482
TI  - Lighting Van Leeuwenhoek's samples.
AB  - Possible techniques for lighting opaque samples while using Van Leeuwenhoek
      microscopes have been tested, and the results are presented in relation to
      published material. The design of the microscope causes the sample to be in
      shadow with any form of top lighting. It is therefore suggested that Van
      Leeuwenhoek's hinted 'particular method of observing' might refer to a different
      style of microscope as shown in the frontispiece of the sale catalogue for his
      microscopes, and available at that time for purchase from sellers of optical
      equipment.

PMID- 29177483
TI  - RE: Regional Nodal Irradiation After Breast-Conserving Surgery for Early HER2
      Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial.

PMID- 29177484
TI  - Social Capital and Life Satisfaction across Older Rural Chinese Groups: Does Age
      Matter?
AB  - This study examined the age difference in the relationship between social capital
      in the form of cognitive (trust, family support) and structural aspects (social
      membership, activity frequency) and life satisfaction of older Chinese people in
      a rural area. Data were collected from 398 elders in the rural area of China by
      quota sampling. Hierarchical regression analysis was used to realize the
      objective. Trust and family support were significantly positively associated with
      life satisfaction, whereas social membership was strongly negatively associated
      with life satisfaction. Activity frequency did not show any significance in
      relationship with life satisfaction. Age difference existed in the associations
      of trust and activity frequency with life satisfaction. Age difference in the
      relationship of trust and activity frequency with life satisfaction of elderly
      Chinese people in the rural area did exist. It is recommended that the measure be
      refined and programs and services be provided according to the hierarchical needs
      of older adults in different age groups.

PMID- 29177485
TI  - Primary care access and foregone care: a survey of transgender adolescents and
      young adults.
AB  - Objective: To examine the issues of primary care access and foregone health care
      among transgender adolescents and young adults. Methods: This cross-sectional
      analysis of data from the Canadian Trans Youth Health Survey was conducted online
      during 2013-2014. Participants included 923 youth aged 14-25 (323 adolescents
      aged 14-18 and 600 young adults aged 19-25). Main outcome measures were self
      reported general and mental health status, comfort discussing transgender
      identity and health care needs with general practitioners, and types of and
      reasons for self-identified foregone health care. Results: Most youth reported
      poor/fair general and mental health status. Comfort with a family doctor was
      positively correlated with both general health (r(528) = 21, P < 0.001) and
      mental health (r(450) = 26, P < 0.001) status, as was having a doctor who was
      aware of one's transgender status. 47.2% (n = 219) of young adults reported
      foregoing needed health care. Among adolescents, levels of comfort with family
      doctor were negatively correlated with foregone mental health care in the
      previous 12 months (F3,166 = 3.829, P = 0.011), but not correlated with foregone
      physical health care (F3,165 = 0.506, P = 0.679). Reasons for missing needed care
      spanned the dimensions of health care access, ranging from cost barriers to
      previous negative experiences with health care providers, and concerns that a
      doctor would be uneducated about transgender people. Conclusion: General
      practitioners can play a key role in improving the health of transgender youth by
      demonstrating understanding of the health care needs of transgender youth and
      competence in gender-affirming care, and by ensuring that their practices are
      accessible to all transgender youth in need of care.

PMID- 29177487
TI  - Being Intentional about Self-Care for Social Workers.

PMID- 29177486
TI  - Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through
      Myenteric Neuronal Mechanisms in Humans.
AB  - Context: Glucagon-like peptide-1 (GLP-1) secretion from l-cells and postprandial
      inhibition of gastrointestinal motility. Objective: Investigate whether
      physiological plasma concentrations of GLP-1 inhibit human postprandial motility
      and determine mechanism of action of GLP-1 and analog ROSE-010 action. Design:
      Single-blind parallel study. Setting: University hospital laboratory.
      Participants: Healthy volunteers investigated with antroduodenal manometry. Human
      gastric and intestinal muscle strips. Interventions: Motility indices (MIs)
      obtained before and during GLP-1 or saline infusion. Plasma GLP-1 and glucagon
      like peptide-2 (GLP-2) measured by radioimmunoassay. Gastrointestinal muscle
      strips investigated for GLP-1- and ROSE-010-induced relaxation employing GLP-1
      and GLP-2 and their receptor localization, and blockers exendin(9-39)amide,
      Lomega-nitro-monomethylarginine (L-NMMA), 2',5'-dideoxyadenosine (DDA), and
      tetrodotoxin (TTX) to reveal target mechanism of GLP-1 action. Main Outcome
      Measures: Postprandial gastrointestinal relaxation by GLP-1. Results: In humans,
      food intake increased MI to 6.4 +/- 0.3 (antrum), 5.7 +/- 0.4 (duodenum), and 5.9
      +/- 0.2 (jejunum). GLP-1 administered intravenously raised plasma GLP-1, but not
      GLP-2. GLP-1 0.7 pmol/kg/min suppressed corresponding MI to 4.6 +/- 0.2, 4.7 +/-
      0.4, and 5.0 +/- 0.2, whereas 1.2 pmol/kg/min suppressed MI to 5.4 +/- 0.2, 4.4
      +/- 0.3, and 5.4 +/- 0.3 (P < 0.0001 to 0.005). In vitro, GLP-1 and ROSE-010
      prevented contractions by bethanechol and electric field stimulation (P < 0.005
      to 0.05). These effects were disinhibited by exendin(9-39)amide, L-NMMA, DDA, or
      TTX. GLP-1 and GLP-2 were localized to epithelial cells, GLP-1 also at myenteric
      neurons. GLP-1R and GLP-2R were localized at myenteric neurons but not muscle.
      Conclusions: GLP-1 and ROSE-010 inhibit postprandial gastrointestinal motility
      through GLP-1R at myenteric neurons, involving nitrergic and cyclic adenosine
      monophosphate-dependent mechanisms.

PMID- 29177488
TI  - A REVIEW OF ANALYTICAL MODELS OF STRAY RADIATION EXPOSURES FROM PHOTON- AND
      PROTON-BEAM RADIOTHERAPIES.
AB  - External-beam radiation therapy is safe, effective and widely used to treat
      cancer. With 5-year cancer survival for adults above 70%, increasingly research
      is focusing on quantifying and reducing treatment-related morbidity. Reducing
      exposures to healthy tissues is one strategy, which can be accomplished with
      advanced-technology radiotherapies, such as intensity-modulated photon therapy
      and proton therapy. Both of these modalities provide good conformation of the
      therapeutic dose to the tumor volume, but they also deliver stray radiation to
      the whole body that increases the risk of radiogenic second cancers. To minimize
      these risks, one needs to create and compare candidate treatment plans that
      explicitly take into account these risks. Currently, clinical practice does not
      include routine calculation of stray radiation exposure and, consequently, the
      assessment of corresponding risks is difficult. In this article, we review recent
      progress toward stray dose algorithms that are suitable for large-scale clinical
      use. In particular, we emphasize the current state of physics-based dose
      algorithms for intensity-modulated photon radiotherapy and proton therapy.

PMID- 29177489
TI  - Disease-based antimicrobial stewardship: a review of active and passive
      approaches to patient management.
AB  - Although new antimicrobial stewardship programmes (ASPs) often begin by targeting
      the reduction of antimicrobial use, an increasing focus of ASPs is to improve the
      management of specific infectious diseases. Disease-based antimicrobial
      stewardship emphasizes improving patient outcomes by optimizing antimicrobial use
      and increasing compliance with performance measures. Directing efforts towards
      the comprehensive management of specific infections allows ASPs to promote the
      shift in healthcare towards improving quality, safety and patient outcome metrics
      for specific diseases. This review evaluates published active and passive disease
      based antimicrobial stewardship interventions and their impact on antimicrobial
      use and associated patient outcomes for patients with pneumonia, acute bacterial
      skin and skin structure infections, bloodstream infections, urinary tract
      infections, asymptomatic bacteriuria, Clostridium difficile infection and intra
      abdominal infections. Current literature suggests that disease-based
      antimicrobial stewardship effects on medical management and patient outcomes vary
      based on infectious disease syndrome, resource availability and intervention
      type.

PMID- 29177490
TI  - Analysis of the influences on plumage condition in laying hens: How suitable is a
      whole body plumage score as an outcome?
AB  - An important indicator of the health and behavior of laying hens is their plumage
      condition. Various scoring systems are used, and various risk factors for feather
      damage have been described. Often, a summarized score of different body parts is
      used to describe the overall condition of the plumage of a bird. However, it has
      not yet been assessed whether such a whole body plumage score is a suitable
      outcome variable when analyzing the risk factors for plumage deterioration. Data
      collected within a German project on farms keeping laying hens in aviaries were
      analyzed to investigate whether and the extent to which information is lost when
      summarizing the scores of the separate body parts. Two models were fitted using
      multiblock redundancy analysis, in which the first model included the whole body
      score as one outcome variable, while the second model included the scores of the
      individual body parts as multiple outcome variables. Although basically similar
      influences could be discovered with both models, the investigation of the
      individual body parts allowed for consideration of the influences on each body
      part separately and for the identification of additional influences. Furthermore,
      ambivalent influences (a factor differently associated with 2 different outcomes)
      could be detected with this approach, and possible dilutive effects were avoided.
      We conclude that influences might be underestimated or even missed when modeling
      their explanatory power for an overall score only. Therefore, multivariate
      methods that allow for the consideration of individual body parts are an
      interesting option when investigating influences on plumage condition.

PMID- 29177491
TI  - Scaling up improvements more quickly and effectively.
AB  - Faster and more widespread implementation could help more patients to benefit
      more quickly from known effective treatments. So could more effective
      implementation of better assessment methods, service delivery models, treatments
      and services. Implementation at scale and 'descaling' are ways for hospitals and
      health systems to respond to rising demands and costs. The paper proposes ways to
      provide leaders with the information that would help them to decide whether and
      how to scale up a proven improvement. We draw on our knowledge of the improvement
      and implementation literature on the subject and on our experience of scale up
      programs in Kaiser Permanente, in Swedish county health systems, and in
      international health. We describe a '3S' scale up infrastructure and other
      ingredients that appear necessary for successful widespread improvement, and list
      the resources that we have found useful for developing scale up programs. The
      paper aims to encourage more actionable research into scale up, and shows the
      opportunities for researchers to both advance implementation and improvement
      science and contribute to reducing suffering and costs in a more timely and
      effective way.

PMID- 29177492
TI  - An artist in surgery and a medical educator.

PMID- 29177493
TI  - Calretinin interneuron density in the caudate nucleus is lower in autism spectrum
      disorder.
AB  - Autism spectrum disorder is a debilitating condition with possible
      neurodevelopmental origins but unknown neuroanatomical correlates. Whereas
      investigators have paid much attention to the cerebral cortex, few studies have
      detailed the basal ganglia in autism. The caudate nucleus may be involved in the
      repetitive movements and limbic changes of autism. We used immunohistochemistry
      for calretinin and neuropeptide Y in 24 age- and gender-matched patients with
      autism spectrum disorder and control subjects ranging in age from 13 to 69 years.
      Patients with autism had a 35% lower density of calretinin+ interneurons in the
      caudate that was driven by loss of small calretinin+ neurons. This was not caused
      by altered size of the caudate, as its cross-sectional surface areas were similar
      between diagnostic groups. Controls exhibited an age-dependent increase in the
      density of medium and large calretinin+ neurons, whereas subjects with autism did
      not. Diagnostic groups did not differ regarding ionized calcium-binding adapter
      molecule 1+ immunoreactivity for microglia, suggesting chronic inflammation did
      not cause the decreased calretinin+ density. There was no statistically
      significant difference in the density of neuropeptide Y+ neurons between subjects
      with autism and controls. The decreased calretinin+ density may disrupt the
      excitation/inhibition balance in the caudate leading to dysfunctional
      corticostriatal circuits. The description of such changes in autism spectrum
      disorder may clarify pathomechanisms and thereby help identify targets for drug
      intervention and novel therapeutic strategies.

PMID- 29177495
TI  - Remote changes after ischaemic infarcts: a distant target for therapy?

PMID- 29177496
TI  - Interaction in isolation: 50 years of insights from split-brain research.

PMID- 29177498
TI  - Discerning the relationship between microglial activation and Alzheimer's
      disease.

PMID- 29177497
TI  - A simple way to distinguish essential tremor from tremulous Parkinson's disease.

PMID- 29177499
TI  - Editorial.

PMID- 29177494
TI  - Domain-general subregions of the medial prefrontal cortex contribute to recovery
      of language after stroke.
AB  - We hypothesized that the recovery of speech production after left hemisphere
      stroke not only depends on the integrity of language-specialized brain systems,
      but also on 'domain-general' brain systems that have much broader functional
      roles. The presupplementary motor area/dorsal anterior cingulate forms part of
      the cingular-opercular network, which has a broad role in cognition and learning.
      Consequently, we have previously suggested that variability in the recovery of
      speech production after aphasic stroke may relate in part to differences in
      patients' abilities to engage this domain-general brain region. To test our
      hypothesis, 27 patients (aged 59 +/- 11 years) with a left hemisphere stroke
      performed behavioural assessments and event-related functional magnetic resonance
      imaging tasks at two time points; first in the early phase (~2 weeks) and then ~4
      months after the ictus. The functional magnetic resonance imaging tasks were
      designed to differentiate between activation related to language production
      (sentential overt speech production-Speech task) and activation related to
      cognitive processing (non-verbal decision making). Simple rest and counting
      conditions were also included in the design. Task-evoked regional brain
      activations during the early and late phases were compared with a longitudinal
      measure of recovery of language production. In accordance with a role in
      cognitive processing, substantial activity was observed within the
      presupplementary motor area/dorsal anterior cingulate during the decision-making
      task. Critically, the level of activation within this region during speech
      production correlated positively with the longitudinal recovery of speech
      production across the two time points (as measured by the in-scanner performance
      in the Speech task). This relationship was observed for activation in both the
      early phase (r = 0.363, P = 0.03 one-tailed) and the late phase (r = 0.538, P =
      0.004). Furthermore, presupplementary motor area/dorsal anterior cingulate
      activity was a predictor of both language recovery over time and language outcome
      at ~4 months, over and above that predicted by lesion volume, age and the initial
      language impairment (general linear model overall significant at P < 0.0001; ExpB
      1.01, P = 0.02). The particularly prominent relationship of the presupplementary
      motor area/dorsal anterior cingulate region with recovery of language was
      confirmed in voxel-wise correlation analysis, conducted unconstrained for the
      whole brain volume. These results accord with the hypothesis that the
      functionality of the presupplementary motor area/dorsal anterior cingulate
      contributes to language recovery after stroke. Given that this brain region is
      often spared in aphasic stroke, we propose that it is a sensible target for
      future research into rehabilitative treatments. More broadly, baseline assessment
      of domain-general systems could help provide a better prediction of language
      recovery.

PMID- 29177500
TI  - Cerebrovascular abnormalities in Alzheimer's dementia: a more tractable treatment
      target?

PMID- 29177501
TI  - A Comparison of Prilocaine vs Prilocaine + Bupivacaine in Periprostatic Block in
      Ambulatory Prostate Biopsies: A Single-Blind Randomized Controlled Study.
AB  - Objective: The purpose of this study was to evaluate the analgesic effect of a
      prilocaine + bupivacaine combination in patients undergoing periprostatic nerve
      block (PNB) by comparing its effects with those of prilocaine alone. Design:
      Single center, single-blind, prospective descriptive study. Subjects: Four
      hundred patients with transrectal prostate biopsy pain. Methods: The patients in
      this prospective, randomized controlled study were divided into two groups. The
      first group received prilocaine during PNB (Group 1), whereas the second received
      a prilocaine + bupivacaine combination (Group 2). Results: The mean visual analog
      scale (VAS) scores immediately after biopsy were 2.52 +/- 0.7 and 2.53 +/- 0.9,
      respectively (P = 0.35). VAS values were significantly lower in Group 2 at one
      and six hours following the procedure. The most painful part of the biopsy
      according to many patients was the probe insertion. Conclusions: The prilocaine +
      bupivacaine combination is an effective analgesic method during prostate biopsies
      and for one and six hours after prostate biopsy.

PMID- 29177502
TI  - Prognostic value of lymph node count on survival in pathologically node-negative
      oesophageal squamous cell cancer.
AB  - OBJECTIVES: This study aims to determine whether lymph node (LN) count is an
      independent predictor of survival in patients with pathologically node-negative
      (pN0) oesophageal squamous cell carcinoma (OSCC). METHODS: Retrospective analysis
      was performed on 194 pN0 OSCC patients undergoing radical oesophagectomy between
      January 2004 and December 2008. The association between the LN count and survival
      was assessed using the Cox proportional hazard model. The optimal LN count cut
      off values were determined using the X-tile program. RESULTS: A total of 10 and
      29 nodes were used as the cut-off values determined by X-tile program.
      Subsequently, all patients were divided into the high-, middle- and low-risk
      subsets in terms of 5-year overall survival rates, which were 36.7%, 56.9% and
      81.8%, respectively (P < 0.001). LN count was also validated as an independent
      prognostic factor in multivariate Cox analysis (P < 0.001; hazard ratio 0.45; 95%
      confidence interval 0.29-0.69). Further analysis showed that patients with 14 or
      more LN count showed a reduced death from OSCC compared with those with less than
      14 LN count (P = 0.002, 5-year overall survival 66% vs 46.5%). CONCLUSIONS: LN
      count exhibits prognostic significance in pN0 OSCC. In addition, the minimum
      number of LNs that should be removed in pN0 OSCC is probably 14.

PMID- 29177503
TI  - Mice with either diminished or elevated levels of anti-Mullerian hormone have
      decreased litter sizes.
AB  - Anti-Mullerian hormone (AMH) is both a gonadal hormone and a putative paracrine
      regulator of neurons, the uterus, and the placenta. A mouse line with neuronal
      expression of AMH (Thy1.2-AMH) was generated to examine the role of paracrine AMH
      in the brain. The mice had normal behavior, but unexpectantly AMH was present in
      the circulation of the transgenic mice. Thy1.2-AMHTg/0 studs sired pups with a
      normal frequency, when mated with wild-type dams. In stark contrast, Thy1.2
      AMHTg/0 dams rarely gave birth, with evidence of spontaneous midgestational
      abortion. This leads to the hypothesis that AMH influences the capacity of dams
      to carry concepti to term. This hypothesis was tested by mating AMH-deficient
      (Amh-/-), Thy1.2-AMHTg/0, and wild-type dams when 49-, 80-, and 111 days old,
      using proven wild-type studs. The litter sizes from the first two matings and the
      number of fetuses present on the 10th day of gestation of the third mating were
      recorded. Thy1.2-AMHTg/0 dams carried near normal numbers of midterm fetuses, but
      typically produced no pups, indicating that extensive late resorption of fetuses
      was occurring. Amh-/- dams exhibited a lesser reduction in litter size than the
      Thy1.2-AMHTg/0 dams, with no evidence of enhanced loss of fetuses. In conclusion,
      this study provides the first evidence that high AMH levels can cause a
      miscarriage phenotype and that the absence of AMH affects reproductive output.

PMID- 29177504
TI  - Pathogenomic Analysis of Wheat Yellow Rust Lineages Detects Seasonal Variation
      and Host Specificity.
AB  - Recent disease outbreaks caused by (re-)emerging plant pathogens have been
      associated with expansions in pathogen geographic distribution and increased
      virulence. For example, in the past two decades' wheat yellow (stripe) rust,
      Puccinia striiformis f. sp. tritici, has seen the emergence of new races that are
      adapted to warmer temperatures, have expanded virulence profiles, and are more
      aggressive than previous races, leading to wide-scale epidemics. Here, we used
      field-based genotyping to generate high-resolution data on P. striiformis
      genetics and carried out global population analysis. We also undertook
      comparative analysis of the 2014 and 2013 UK populations and assessed the
      temporal dynamics and host specificity of distinct pathogen genotypes. Our
      analysis revealed that P. striiformis lineages recently detected in Europe are
      extremely diverse and in fact similar to globally dispersed populations. In
      addition, we identified a considerable shift in the UK P. striiformis population
      structure including the first identification of one infamous race known as
      Kranich. Next, by establishing the genotype of both the pathogen and host within
      a single infected field sample, we uncovered evidence for varietal specificity
      for genetic groups of P. striiformis. Finally, we found potential seasonal
      specificity for certain genotypes of the pathogen with several lineages
      identified only in samples collected in late spring and into the summer, whereas
      one lineage was identified throughout the wheat growing season. Our discovery of
      which wheat varieties are susceptible to which specific P. striiformis isolates,
      and when those isolates are prevalent throughout the year, represents a powerful
      tool for disease management.

PMID- 29177505
TI  - Efficient RNA pseudouridylation by eukaryotic H/ACA ribonucleoproteins requires
      high affinity binding and correct positioning of guide RNA.
AB  - H/ACA ribonucleoproteins (H/ACA RNPs) are responsible for introducing many
      pseudouridines into RNAs, but are also involved in other cellular functions.
      Utilizing a purified and reconstituted yeast H/ACA RNP system that is active in
      pseudouridine formation under physiological conditions, we describe here the
      quantitative characterization of H/ACA RNP formation and function. This analysis
      reveals a surprisingly tight interaction of H/ACA guide RNA with the Cbf5p-Nop10p
      Gar1p trimeric protein complex whereas Nhp2p binds comparably weakly to H/ACA
      guide RNA. Substrate RNA is bound to H/ACA RNPs with nanomolar affinity which
      correlates with the GC content in the guide-substrate RNA base pairing. Both
      Nhp2p and the conserved Box ACA element in guide RNA are required for efficient
      pseudouridine formation, but not for guide RNA or substrate RNA binding. These
      results suggest that Nhp2p and the Box ACA motif indirectly facilitate loading of
      the substrate RNA in the catalytic site of Cbf5p by correctly positioning the
      upper and lower parts of the H/ACA guide RNA on the H/ACA proteins. In summary,
      this study provides detailed insight into the molecular mechanism of H/ACA RNPs.

PMID- 29177506
TI  - LRRK2 phosphorylates membrane-bound Rabs and is activated by GTP-bound Rab7L1 to
      promote recruitment to the trans-Golgi network.
AB  - Human genetic studies implicate LRRK2 and RAB7L1 in susceptibility to Parkinson
      disease (PD). These two genes function in the same pathway, as knockout of Rab7L1
      results in phenotypes similar to LRRK2 knockout, and studies in cells and model
      organisms demonstrate LRRK2 and Rab7L1 interact in the endolysosomal system.
      Recently, a subset of Rab proteins have been identified as LRRK2 kinase
      substrates. Herein, we find that Rab8, Rab10, and Rab7L1 must be membrane and GTP
      bound for LRRK2 phosphorylation. LRRK2 mutations that cause PD including R1441C,
      Y1699C, and G2019S all increase LRRK2 phosphorylation of Rab7L1 four-fold over
      wild-type LRRK2 in cells, resulting in the phosphorylation of nearly one-third
      the available Rab7L1 protein in cells. In contrast, the most common pathogenic
      LRRK2 mutation, G2019S, does not upregulate LRRK2-mediated phosphorylation of
      Rab8 or Rab10. LRRK2 interaction with membrane and GTP-bound Rab7L1, but not Rab8
      or Rab10, results in the activation of LRRK2 autophosphorylation at the serine
      1292 position, required for LRRK2 toxicity. Further, Rab7L1 controls the
      proportion of LRRK2 that is membrane-associated, and LRRK2 mutations enhance
      Rab7L1-mediated recruitment of LRRK2 to the trans-Golgi network. Interaction
      studies with the Rab8 and Rab10 GTPase-activating protein TBC1D4/AS160
      demonstrate that LRRK2 phosphorylation may block membrane and GTP-bound Rab
      protein interaction with effectors. These results suggest reciprocal regulation
      between LRRK2 and Rab protein substrates, where Rab7L1-mediated upregulation of
      LRRK2 kinase activity results in the stabilization of membrane and GTP-bound Rab
      proteins that may be unable to interact with Rab effector proteins.

PMID- 29177507
TI  - A randomized Phase III trial of lobe-specific vs. systematic nodal dissection for
      clinical Stage I-II non-small cell lung cancer (JCOG1413).
AB  - In January 2017, the Lung Cancer Surgical Study Group of the Japan Clinical
      Oncology Group commenced a randomized Phase III trial to confirm the clinical
      benefit of lobe-specific nodal dissection for clinical Stage I-II non-small cell
      lung cancer. The primary endpoint is overall survival, and the main objective is
      to confirm the non-inferiority of lobe-specific in comparison to systematic nodal
      dissection with regard to lobectomy. The secondary endpoints are relapse-free
      survival, %local recurrence, %regional lymph node recurrence, operation time,
      blood loss, length of hospitalization, duration of chest tube placement and
      adverse events. A total of 1700 patients will be accrued from 44 Japanese
      institutions within 5 years. This study is the first and large prospective trial
      to evaluate whether the difference in the area of nodal dissection affects the
      overall survival of patients with relatively early-stage non-small cell lung
      cancer. This trial has been registered in the UMIN Clinical Trials Registry as
      UMIN000025530.

PMID- 29177508
TI  - MVP: a microbe-phage interaction database.
AB  - Phages invade microbes, accomplish host lysis and are of vital importance in
      shaping the community structure of environmental microbiota. More importantly,
      most phages have very specific hosts; they are thus ideal tools to manipulate
      environmental microbiota at species-resolution. The main purpose of MVP (Microbe
      Versus Phage) is to provide a comprehensive catalog of phage-microbe interactions
      and assist users to select phage(s) that can target (and potentially to
      manipulate) specific microbes of interest. We first collected 50 782 viral
      sequences from various sources and clustered them into 33 097 unique viral
      clusters based on sequence similarity. We then identified 26 572 interactions
      between 18 608 viral clusters and 9245 prokaryotes (i.e. bacteria and archaea);
      we established these interactions based on 30 321 evidence entries that we
      collected from published datasets, public databases and re-analysis of genomic
      and metagenomic sequences. Based on these interactions, we calculated the host
      range for each of the phage clusters and accordingly grouped them into subgroups
      such as 'species-', 'genus-' and 'family-' specific phage clusters. MVP is
      equipped with a modern, responsive and intuitive interface, and is freely
      available at: http://mvp.medgenius.info.

PMID- 29177510
TI  - Disseminated Cryptococcosis Presenting as Miliary Lung Shadows in an
      Immunocompetent Child.
AB  - Disseminated cryptococcosis is infrequent in immunocompetent children. Pulmonary
      and central nervous system are the commonly involved sites of infection in an
      immunocompromised host. We report a fatal case of disseminated cryptococcosis in
      an immunocompetent host presenting as fever of unknown origin with miliary
      shadows on chest radiograph, mimicking tuberculosis. In countries with the heavy
      burden of tuberculosis, a high index of suspicion is needed for early diagnosis
      of its close mimics like disseminated cryptococcosis.

PMID- 29177509
TI  - Repetitive behaviors in autism are linked to imbalance of corticostriatal
      connectivity: a functional connectivity MRI study.
AB  - The neural underpinnings of repetitive behaviors (RBs) in autism spectrum
      disorders (ASDs), ranging from cognitive to motor characteristics, remain
      unknown. We assessed RB symptomatology in 50 ASD and 52 typically developing (TD)
      children and adolescents (ages 8-17 years), examining intrinsic functional
      connectivity (iFC) of corticostriatal circuitry, which is important for reward
      based learning and integration of emotional, cognitive and motor processing, and
      considered impaired in ASDs. Connectivity analyses were performed for three
      functionally distinct striatal seeds (limbic, frontoparietal and motor).
      Functional connectivity with cortical regions of interest was assessed for
      corticostriatal circuit connectivity indices and ratios, testing the balance of
      connectivity between circuits. Results showed corticostriatal overconnectivity of
      limbic and frontoparietal seeds, but underconnectivity of motor seeds.
      Correlations with RBs were found for connectivity between the striatal motor
      seeds and cortical motor clusters from the whole-brain analysis, and for
      frontoparietal/limbic and motor/limbic connectivity ratios. Division of ASD
      participants into high (n = 17) and low RB subgroups (n = 19) showed reduced
      frontoparietal/limbic and motor/limbic circuit ratios for high RB compared to low
      RB and TD groups in the right hemisphere. Results suggest an association between
      RBs and an imbalance of corticostriatal iFC in ASD, being increased for limbic,
      but reduced for frontoparietal and motor circuits.

PMID- 29177511
TI  - Corrigenda: The Prevalence of Dementia and Cognitive Impairment in our Acute
      Medical Admissions.

PMID- 29177512
TI  - "The Lesser of Two Evils" Versus "Medicines not Smarties": Constructing
      Antipsychotics in Dementia.
AB  - Background and Objectives: Because antipsychotics are associated with an
      increased risk of morbidity and mortality, they should only be prescribed in
      dementia in limited circumstances. But antipsychotics are prescribed to a large
      proportion of residents in formal care settings despite guidance and warnings to
      the contrary, justifying a study into how professionals define and in turn create
      realities about antipsychotic usage in dementia. Research Design and Methods:
      Twenty-eight professionals with a role in the care and management of patients
      with dementia in care homes were recruited and interviewed in this qualitative
      study. A gap in the literature about the social construction of antipsychotics in
      dementia prompted the use of critical discourse analysis methodology. Results:
      Antipsychotics were portrayed in 2 distinct ways; as "the lesser of two evils'
      they were conceptualized as the less harmful or unpleasant of 2 bad choices and
      as "medicines not Smarties" (a brand of sweets/candy) they were conceptualized as
      prescribed too frequently and indiscriminately. The first resource could be used
      to defend the prescribing of antipsychotics and uphold the prescribers' privilege
      to do so whereas the second enabled the speaker to reject their own wilful
      involvement in overprescribing. Discussion and Implications: When prescribers
      draw on "the lesser of two evils" paradigm to sanction the overprescribing of
      antipsychotics, implicit assumptions about these medications as being the best of
      bad choices should be recognized and challenged. Future studies should target
      specific normative beliefs about antipsychotic prescribing consequences, to
      change the lexicon of common knowledge which perpetuates bad practice.

PMID- 29177513
TI  - Multiple Regulatory Modules Are Required for Scale-to-Feather Conversion.
AB  - The origin of feathers is an important question in Evo-Devo studies, with the
      eventual evolution of vaned feathers which are aerodynamic, allowing feathered
      dinosaurs and early birds to fly and venture into new ecological niches. Studying
      how feathers and scales are developmentally specified provides insight into how a
      new organ may evolve. We identified feather-associated genes using genomic
      analyses. The candidate genes were tested by expressing them in chicken and
      alligator scale forming regions. Ectopic expression of these genes induced
      intermediate morphotypes between scales and feathers which revealed several major
      morphogenetic events along this path: Localized growth zone formation, follicle
      invagination, epithelial branching, feather keratin differentiation, and dermal
      papilla formation. In addition to molecules known to induce feathers on scales
      (retinoic acid, beta-catenin), we identified novel scale-feather converters
      (Sox2, Zic1, Grem1, Spry2, Sox18) which induce one or more regulatory modules
      guiding these morphogenetic events. Some morphotypes resemble filamentous
      appendages found in feathered dinosaur fossils, whereas others exhibit
      characteristics of modern avian feathers. We propose these morpho-regulatory
      modules were used to diversify archosaur scales and to initiate feather
      evolution. The regulatory combination and hierarchical integration may have led
      to the formation of extant feather forms. Our study highlights the importance of
      integrating discoveries between developmental biology and paleontology.

PMID- 29177516
TI  - NEUTRON WORKPLACE SPECTROMETRY (ENERGY AND DIRECTION) USING TL DETECTORS: FIRST
      APPROACH AND RESPONSE FUNCTIONS.
AB  - The response of albedo dosemeters depends on the energy and angle of the incident
      neutron radiation. For their use as personal dosemeters, a field-calibration
      factor has to be applied. The presently used single sphere method for field
      calibration can be extended and optimised by putting five albedo dosemeters on
      the surface of a polyethylene sphere and two TL cards in the centre. To
      investigate the potential of this extension, reference measurements and Monte
      Carlo calculations were performed and the fluence response of the detectors at
      different positions on and within the sphere was determined. Calculated response
      functions demonstrate that information on the energy and directional distribution
      of neutron fluence can be extracted with this simple set-up for unknown neutron
      fields.

PMID- 29177515
TI  - Clinical Aspects of SDHA-Related Pheochromocytoma and Paraganglioma: A Nationwide
      Study.
AB  - Context: Paraganglioma (PGL) has the highest degree of heritability among human
      neoplasms. Current clinical understanding of germline SDHA mutation carriers is
      limited. Objective: To estimate the contribution of SDHA mutations in PGL and to
      assess clinical manifestations and age-related penetrance. Design: Nationwide
      retrospective cohort study. Setting: Tertiary referral centers in the Netherlands
      (multicenter). Patients: Germline SDHA analysis was performed in 393 patients
      with genetically unexplained PGL. Subsequently, 30 index SDHA mutation carriers
      and 56 nonindex carriers were studied. Main Outcome Measures: SDHA mutation
      detection yield, clinical manifestations, and SDHA-related disease penetrance.
      Results: Pathogenic germline SDHA variants were identified in 30 of the 393
      referred patients with PGL (7.6%), who had head and neck PGL (21 of 174 [12%]),
      pheochromocytoma (4 of 191 [2%]), or sympathetic PGL (5 of 28 [18%]). The median
      age at diagnosis was 43 years (range, 17 to 81 years) in index SDHA mutation
      carriers compared with 52 years (range, 7 to 90 years) in nonmutation carriers (P
      = 0.002). The estimated penetrance of any SDHA-related manifestation was 10% at
      age 70 years (95% confidence interval, 0% to 21%) in nonindex mutation carriers.
      Conclusion: Germline SDHA mutations are relatively common (7.6%) in patients with
      genetically unexplained PGL. Most index patients presented with apparently
      sporadic PGL. In this SDHA series, the largest assembled so far, we found the
      lowest penetrance of all major PGL predisposition genes. This suggests that
      recommendations for genetic counseling of at-risk relatives and stringency of
      surveillance for SDHA mutation carriers might need to be reassessed.

PMID- 29177514
TI  - Transcriptome analysis of Pinus halepensis under drought stress and during
      recovery.
AB  - Forest trees use various strategies to cope with drought stress and these
      strategies involve complex molecular mechanisms. Pinus halepensis Miller (Aleppo
      pine) is found throughout the Mediterranean basin and is one of the most drought
      tolerant pine species. In order to decipher the molecular mechanisms that P.
      halepensis uses to withstand drought, we performed large-scale physiological and
      transcriptome analyses. We selected a mature tree from a semi-arid area with
      suboptimal growth conditions for clonal propagation through cuttings. We then
      used a high-throughput experimental system to continuously monitor whole-plant
      transpiration rates, stomatal conductance and the vapor pressure deficit. The
      transcriptomes of plants were examined at six physiological stages: pre-stomatal
      response, partial stomatal closure, minimum transpiration, post-irrigation,
      partial recovery and full recovery. At each stage, data from plants exposed to
      the drought treatment were compared with data collected from well-irrigated
      control plants. A drought-stressed P. halepensis transcriptome was created using
      paired-end RNA-seq. In total, ~6000 differentially expressed, non-redundant
      transcripts were identified between drought-treated and control trees. Cluster
      analysis has revealed stress-induced down-regulation of transcripts related to
      photosynthesis, reactive oxygen species (ROS)-scavenging through the ascorbic
      acid (AsA)-glutathione cycle, fatty acid and cell wall biosynthesis, stomatal
      activity, and the biosynthesis of flavonoids and terpenoids. Up-regulated
      processes included chlorophyll degradation, ROS-scavenging through AsA
      independent thiol-mediated pathways, abscisic acid response and accumulation of
      heat shock proteins, thaumatin and exordium. Recovery from drought induced strong
      transcription of retrotransposons, especially the retrovirus-related transposon
      Tnt1-94. The drought-related transcriptome illustrates this species' dynamic
      response to drought and recovery and unravels novel mechanisms.

PMID- 29177517
TI  - My Brother Patrick's Dying Wish.

PMID- 29177519
TI  - Stock Art Concern.

PMID- 29177522
TI  - Nurses' Role in Managing "The Fit" of Older Adults in Skilled Nursing Facilities.
AB  - Post-acute care for older adults often involves transfer to a skilled nursing
      facility (SNF) following hospital discharge. This transition is often poorly
      coordinated and leaves older adults at risk for poor health outcomes, but new
      payment models offer opportunities to align improved care practices with
      payments. There is a dearth of evidence regarding the role of nursing and its
      potential to improve hospital to SNF care transitions. Ninety-nine semi
      structured interviews were conducted with clinicians, patients, and caregivers
      from three hospitals and three SNFs. Results indicate a sharp contrast in the
      roles of hospital nurses-who are often silent partners in post-acute care
      decision making-and SNF nurses, who take a primary role as managing "the fit" for
      patients transitioning to a SNF. Nurses are uniquely positioned to make needed
      changes to culture to adapt to new payment models and improve patient outcomes.
      [Journal of Gerontological Nursing, 43(12), 11-20.].

PMID- 29177523
TI  - Obesity: A Problem for All of Us.

PMID- 29177524
TI  - Measuring Success: Goals and Outcomes for Educational Programs.
AB  - Measuring outcomes for educational programs can be challenging for many nursing
      professional development (NPD) practitioners. Alignment of goals with outcomes
      provides the foundation for the educator to justify, evaluate, and improve
      programs with more efficiency. This article highlights lessons learned by NPD
      practitioners after successful justification for continued support of educational
      programs. J Contin Nurs Educ. 2017;48(12):537-538.

PMID- 29177525
TI  - Designing Education for Learning Activation.
AB  - Preparing adult learners to bring their expertise to improve new processes
      requires learner activation. Once learners are fully activated, they can bring
      their unique perspective to apply knowledge and facilitate change. For nurses,
      who are closest to the patient, activating the nursing perspective to continue to
      improve on the changes that will continue to pervade health care is critical.
      This is the role of the professional development educator. J Contin Educ Nurs.
      2017;48(12):539-540.

PMID- 29177526
TI  - Using Social Media to Support Clinical Education.
AB  - Social media has been used increasingly as part of nursing education. Nurse
      educators at a large, multisite teaching hospital used social media to support
      clinical teaching. A series of educational images was created by nurse educators
      and shared across Facebook, Twitter, and Instagram. This campaign coincided with
      in-unit clinical education. Nurse educators can consider using social media as an
      adjunct to clinical teaching, especially in large hospital settings. J Contin
      Educ Nurs. 2017;48(12):541-542.

PMID- 29177527
TI  - Lessons Learned From a Theory of Planned Behavior-Derived Study on Educational
      Interventions Inspired by the Affective Domain.
AB  - BACKGROUND: A paucity of literature exists on use of the affective domain to
      improve adherence to pressure injury prevention. The purpose of this study was to
      assess the use of emphasizing the cognitive domain versus education based on
      combination of the affective and cognitive domains focusing on medical-surgical
      nurses' behavioral intent to use evidence-based practices to prevent pressure
      injury. METHOD: A cluster randomized, controlled design was used to compare
      differences between groups. Medical-surgical nurses in units with low performance
      in pressure ulcer prevention were studied. A total of 77 nurses participated.
      This study employed the theory of planned behavior. RESULTS: Attitudes toward
      pressure ulcer predicted behavioral intent. Nurses who experienced the affective
      domain education showed improvements over the control group for attitude and
      perceived behavioral control. CONCLUSION: Affective domain interventions have the
      potential to favorably impact nurses in valuing pressure ulcer prevention,
      despite any barriers. J Contin Educ Nurs. 2017;48(12):543-551.

PMID- 29177528
TI  - Professor in Residence: An Innovative Academic-Practice Partnership.
AB  - This article describes an academic-practice partnership between an American
      Nurses Credentialing Center Magnet(r)-designated hospital and an academic nurse
      educator that has increased the hospital's capacity for research, evidence-based
      practice, and support for nurses continuing their education. Through close
      collaboration with the full-time nurse researcher and members of the nursing
      education department, the professor in residence consults with clinical staff to
      support completion of research and evidence-based practice projects. The
      collaboration also has resulted in the development of a formal year-long
      mentoring program for clinical nurses in the area of evidence-based practice.
      Individual support and academic consults are offered to nurses enrolled in school
      to promote advancement of nurses' educational level. This collaboration has been
      beneficial for both the hospital and the university, increasing the capacity for
      scholarly activities for nurses in the hospital and serving as a forum for
      ongoing faculty practice and scholarship. J Contin Educ Nurs. 2017;48(12):552
      556.

PMID- 29177529
TI  - A Health Care-Academic Partnership: Developing Pediatric Nursing Education.
AB  - An acute care pediatric hospital and a university school of nursing joined forces
      to develop a comprehensive, interactive, online course in pediatric health
      assessment. The course was intended to increase nurses' knowledge and confidence
      in caring for children and families. The need for pediatric health assessment
      education varies depending on learners' prior experience. This article describes
      the course development and shares insights into the successful health care
      academic partnership, which combined clinical, scholarly, and technological
      expertise. J Contin Educ Nurs. 2017;48(12):557-562.

PMID- 29177530
TI  - Innovative Team Training for Patient Safety: Comparing Classroom Learning to
      Experiential Training.
AB  - This study compared two different means of retraining staff in TeamSTEPPS(r) in
      an effort to determine whether experiential training might be more effective than
      a classroom experience. A randomized, controlled pretest-posttest repeated
      measures design was used for the study. The hypothesis that experiential classes
      would result in improvements in attitude, perceptions, and knowledge of
      TeamSTEPPS was not borne out, but several important implications for further
      study were discovered. J Contin Educ Nurs. 2017;48(12):563-569.

PMID- 29177531
TI  - Knowledge Level and Educational Needs of Turkish Oncology Nurses Regarding the
      Genetics of Hereditary Breast and Ovarian Cancer.
AB  - BACKGROUND: This study evaluated Turkish oncology nurses' knowledge and
      educational needs regarding genetics of hereditary breast and ovarian cancers.
      METHOD: An online survey was used to collect data from 104 Turkish oncology
      nurses. RESULTS: The mean level of knowledge in oncology genetics was 6.74 +/-
      3.85. The majority of nurses (78.7%) were aware of the fact that family history
      of ovarian or breast cancer is an important risk factor for ovarian or breast
      cancer; however, a much smaller percentage (25.5%) understood that BRCA1
      mutations in women can be transferred by the father. The majority of the nurses
      (59.6%) were willing to take continuing education in cancer genetics. CONCLUSION:
      Turkish oncology nurses have a moderate level of knowledge in cancer genetics.
      Therefore, educators should develop targeted educational activities in genetics
      as a part of continuing education programs to enhance nursing practice in cancer
      care. J Contin Educ Nurs. 2017;48(12):570-576.

PMID- 29177532
TI  - [A different kind of wrestler's ear].
AB  - We report the case of a 19-year-old patient who presented with recurrent circular
      and scaly skin changes. The patient reported wrestling as his main leisure
      activity. After an unsuccessful attempt at local antibiotic treatment, detailed
      dermatological work-up revealed the skin changes to be tinea corporis
      gladiatorum. According to dermatological guidelines for dermatophytosis, systemic
      treatment with fluconazole and local ointments containing ciclopirox olamine and
      ketoconazole were administered, which rapidly led to significant improvement.

PMID- 29177533
TI  - Focus on traumatic brain injury.

PMID- 29177536
TI  - Novel biotechnological platform based on baculovirus occlusion bodies carrying
      Babesia bovis small antigenic peptides for the design of a diagnostic enzyme
      linked immunosorbent assay (ELISA).
AB  - Baculoviruses are large DNA virus of insects principally employed in recombinant
      protein expression. Its ability to form occlusion bodies (OBs), which are
      composed mainly of polyhedrin protein (POLH), makes them biotechnologically
      attractive, as these crystals (polyhedra) can incorporate foreign peptides and
      can be easily isolated. On the other hand, peptide microarrays allow rapid and
      inexpensive high-throughput serological screening of new candidates to be
      incorporated to OBs. To integrate these 2 biotechnological approaches, we worked
      on Babesia bovis, one of the causative agents of bovine babesiosis. Current
      molecular diagnosis of infection with B. bovis includes enzyme-linked
      immunosorbent assay (ELISA) techniques, which use merozoite lysate obtained from
      infected bovine erythrocytes. However, it is important to produce recombinant
      antigens that replace the use of crude antigens. Here, we describe a new
      biotechnological platform for the design of indirect ELISAs based on 5 antigenic
      peptides of 15 amino acid residues of B. bovis (ApBb), selected from a peptide
      microarray and expressed as a fusion to POLH. An Sf9POLHE44G packaging cell line
      infected with recombinant baculoviruses carrying POLH-ApBb fusions yielded higher
      levels of chimeric polyhedra, highlighting the advantage of a trans-contribution
      of a mutant copy of polyhedrin. Finally, the use of dissolved recombinant
      polyhedra as antigens was successful in an ELISA assay, as B. bovis-positive sera
      recognized the fusion POLH-ApBb. Thus, the use of this platform resulted in a
      promising alternative for molecular diagnosis of relevant infectious diseases.

PMID- 29177534
TI  - Structural variations in wheat HKT1;5 underpin differences in Na+ transport
      capacity.
AB  - An important trait associated with the salt tolerance of wheat is the exclusion
      of sodium ions (Na+) from the shoot. We have previously shown that the sodium
      transporters TmHKT1;5-A and TaHKT1;5-D, from Triticum monoccocum (Tm) and
      Triticum aestivum (Ta), are encoded by genes underlying the major shoot Na+
      exclusion loci Nax1 and Kna1, respectively. Here, using heterologous expression,
      we show that the affinity (K m) for the Na+ transport of TmHKT1;5-A, at 2.66 mM,
      is higher than that of TaHKT1;5-D at 7.50 mM. Through 3D structural modelling, we
      identify residues D471/a gap and D474/G473 that contribute to this property. We
      identify four additional mutations in amino acid residues that inhibit the
      transport activity of TmHKT1;5-A, which are predicted to be the result of an
      occlusion of the pore. We propose that the underlying transport properties of
      TmHKT1;5-A and TaHKT1;5-D contribute to their unique ability to improve Na+
      exclusion in wheat that leads to an improved salinity tolerance in the field.

PMID- 29177535
TI  - Genome-wide association study of stem rust resistance in a world collection of
      cultivated barley.
AB  - KEY MESSAGE: QTL conferring a 14-40% reduction in adult plant stem rust severity
      to multiple races of Pgt were found on chromosome 5H and will be useful in barley
      breeding. Stem rust, caused by Puccinia graminis f. sp. tritici (Pgt) is an
      important disease of barley. The resistance gene Rpg1 has protected the crop
      against stem rust losses for over 70 years in North America, but is not effective
      against the African Pgt race TTKSK (and its variants) nor the domestic race
      QCCJB. To identify resistance to these Rpg1-virulent races, the Barley iCore
      Collection, held by the United States Department of Agriculture-Agricultural
      Research Service National Small Grains Collection was evaluated for adult plant
      resistance (APR) and seedling resistance to race TTKSK and APR to race QCCJB and
      the Pgt TTKSK composite of races TTKSK, TTKST, TTKTK, and TTKTT. Using a genome
      wide association study approach based on 6224 single nucleotide polymorphic
      markers, seven significant loci for stem rust resistance were identified on
      chromosomes 1H, 2H, 3H, and 5H. The most significant markers detected were
      11_11355 and SCRI_RS_177017 at 71-75 cM on chromosome 5H, conferring APR to QCCJB
      and TTKSK composite. Significant markers were also detected for TTKSK seedling
      resistance on chromosome 5H. All markers detected on 5H were independent of the
      rpg4/Rpg5 complex at 152-168 cM. This study verified the importance of the
      11_11355 locus in conferring APR to races QCCJB and TTKSK and suggests that it
      may be effective against other races in the Ug99 lineage.

PMID- 29177537
TI  - Distinguishing child abuse fractures from rickets.

PMID- 29177538
TI  - Invited editorial for the paper by Silvoniemi et al. "Repeatability of tumor
      hypoxia imaging using [18F]EF5 PET/CT in head and neck cancer." in this issue of
      EJNMMI.

PMID- 29177539
TI  - Does FeNO Predict Clinical Characteristics in Chronic Cough?
AB  - PURPOSE: To evaluate whether exhaled nitric oxide measurement can facilitate in
      the assessment of chronic cough patients based on their airway inflammatory
      phenotype. METHODS: We have studied consecutive patients attending a specialist
      cough clinic. 30 patients with high FeNO (> 30 ppb) and 20 patients with low FeNO
      (< 20 ppb) were recruited. RESULTS: There was a significant correlation between
      FeNO, B-Eos and sputum eosinophil count (p < 0.001). The number of recorded
      coughs in 24 h and HARQ scores were significantly (p < 0.05) higher in patients
      with a low FeNO. In contrast to the high FeNO group (48%), the greater proportion
      of these patients were women (90%). LCQ scores were worse in the low FeNO group
      but it was not significant. CONCLUSION: A strong relationship between FeNO, blood
      eosinophils and sputum eosinophils confirming phenotypic identity was observed.
      Whether the observed gender disparity accounts for the different cough frequency
      characteristics is unknown.

PMID- 29177540
TI  - The distance of the gluteal nerve in relation to anatomical landmarks: an
      anatomic study.
AB  - INTRODUCTION: Gluteal insufficiency is of concern with lateral approaches to
      total hip arthroplasty. Damage to the branches of the superior gluteal nerve may
      cause degeneration of the innervated muscles. The direct anterior approach
      exploits the intermuscular and internerval interval between tensor fasciae latae
      laterally and sartorius and rectus femoris muscle medially. In this study, the
      distance of the superior gluteal nerve in relation to anatomical landmarks was
      determined. MATERIALS AND METHODS: Two experienced surgeons implanted trial
      components in 15 alcohol glycerol fixed cadavers with 30 hips. The trials were
      removed, and the main branch of the superior gluteal nerve and muscular branches
      of the nerve were exposed from lateral. RESULTS: No visual damage to the main
      nerve branches and the location of the nerve in relation to the greater
      trochanter were noted by an experienced surgeon. The superior gluteal nerve and
      its muscular branches crossed the muscular interval between the gluteus medius
      and tensor fasciae latae muscles at a mean distance of 39 mm from the tip of the
      greater trochanter. CONCLUSIONS: The direct anterior approach for total hip
      arthroplasty minimizes the risk of injuring the superior gluteal nerve, which may
      result in a gluteal insufficiency. Special care should be paid on avoiding
      overstretching the tensor fasciae latea muscle using minimum force on retractors
      during surgery and by taking care of the entrance point of the superior gluteal
      nerve to the tensor fasciae latae.

PMID- 29177541
TI  - Combined CT-based and image-free navigation systems in TKA reduces postoperative
      outliers of rotational alignment of the tibial component.
AB  - INTRODUCTION: Rotational malpositioning of the tibial component can lead to poor
      functional outcome in TKA. Although various surgical techniques have been
      proposed, precise rotational placement of the tibial component was difficult to
      accomplish even with the use of a navigation system. The purpose of this study is
      to assess whether combined CT-based and image-free navigation systems replicate
      accurately the rotational alignment of tibial component that was preoperatively
      planned on CT, compared with the conventional method. MATERIALS AND METHODS: We
      compared the number of outliers for rotational alignment of the tibial component
      using combined CT-based and image-free navigation systems (navigated group) with
      those of conventional method (conventional group). Seventy-two TKAs were
      performed between May 2012 and December 2014. In the navigated group, the
      anteroposterior axis was prepared using CT-based navigation system and the tibial
      component was positioned under control of the navigation. In the conventional
      group, the tibial component was placed with reference to the Akagi line that was
      determined visually. Fisher's exact probability test was performed to evaluate
      the results. RESULTS: There was a significant difference between the two groups
      with regard to the number of outliers: 3 outliers in the navigated group compared
      with 12 outliers in the conventional group (P < 0.01). CONCLUSIONS: We concluded
      that combined CT-based and image-free navigation systems decreased the number of
      rotational outliers of tibial component, and was helpful for the replication of
      the accurate rotational alignment of the tibial component that was preoperatively
      planned.

PMID- 29177542
TI  - Adjustable transobturator sling for the treatment of primary stress urinary
      incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of the study was to evaluate the rate of
      postoperative voiding dysfunction after the insertion of an adjustable
      transobturator sling for the treatment of primary stress urinary incontinence
      (SUI). The secondary aim was to assess the objective and subjective cure rates
      and the impact of the surgery on quality of life. METHODS: This prospective study
      included 171 patients with primary SUI who underwent insertion of an adjustable
      transobturator tape. A postoperative tension adjustment algorithm that included a
      cough stress test (CST), uroflowmetry and postvoid residual volume (PVR)
      measurement was applied in all patients the day after surgery. The baseline and
      control postoperative evaluations included vaginal examination, CST, Q-tip test,
      uroflowmetry and PVR measurement, 1-h pad test and administration questionnaires
      (UDI-6, IIQ-7, PISQ-12, ICIQ-SF). RESULTS: The day after surgery 65 patients
      (38.0%) required tape tension adjustment: an increase in tension in 53 patients
      (31.0%) and a decrease in 12 (7.0%). Continence was achieved in all patients. No
      patients showed voiding dysfunction after adjustment. Follow-up data for 12
      months were available in 157 patients (91.8%). The objective and subjective cure
      rates were 96.2% and 97.5%, respectively. There was no statistically significant
      decrease in Qmax (p = 0.899) or increase in PVR (p = 0.187). According to the
      questionnaires scores, quality of life was improved in all patients. CONCLUSION:
      The adjustable transobturator sling minimizes the risk of postoperative voiding
      dysfunction and allows high objective and subjective cure rates to be achieved in
      patients with primary SUI. The technique also improves the patient's quality of
      life.

PMID- 29177543
TI  - Comment on "Detrusor pressures in urodynamic studies during voiding in women".

PMID- 29177544
TI  - Are the same tapes really the same? Ultrasound study of laser-cut and
      mechanically cut TVT-O post-operative behavior.
AB  - INTRODUCTION AND HYPOTHESIS: TVT-O production has been modified to laser cutting
      from mechanical cutting. We compared the behavior of laser and mechanically cut
      tension-free vaginal tape-obturator (TVT-O) using ultrasound at various time
      points after surgery. METHODS: This is a retrospective analysis of clinical and
      ultrasound data from two previously reported randomized controlled trials with
      TVT-O. Behavior of mechanically cut TVT-O implanted in January 2007 to November
      2009 and laser-cut TVT-O implanted in May 2010 to May 2012 was assessed by
      ultrasound at day 1, the 2nd week, the 3rd month, and the 1st and 2nd years post
      operatively. Bladder neck and tape margins positions were described by
      coordinates in the orthogonal system calculated from polar coordinates. Tape
      mobility was measured as a change in the upper and lower tape margin position
      from rest to maximal Valsalva. Comparison of 2-year subjective and objective
      surgery outcomes was also performed. RESULTS: In total, 68 mechanically cut and
      50 laser-cut TVT-Os were implanted. Follow-up data were available from 49 and 45
      women respectively. No differences in any baseline characteristics or bladder
      neck mobility were observed. Significantly lower tape mobility was observed on
      day 1 and week 2 after mechanically cut TVT-O, although subsequent mobility was
      comparable to laser-cut TVT-O. The subjective and objective surgery outcomes were
      comparable. CONCLUSIONS: Although without clinical significance, early
      postoperative behavior of the mechanically cut and laser-cut TVT-O tapes differs.
      The less stiff, mechanically-cut TVT-O loosens within 2 weeks of implantation,
      whereas the stiffer, laser-cut TVT-O keeps its tension.

PMID- 29177545
TI  - Porcine teschovirus 2 induces an incomplete autophagic response in PK-15 cells.
AB  - Autophagy is a homeostatic process that has been shown to be vital in the innate
      immune defense against pathogens. However, little is known about the regulatory
      role of autophagy in porcine teschovirus 2 (PTV-2) replication. In this study, we
      found that PTV-2 infection induces a strong increase in GFP-LC3 punctae and
      endogenous LC3 lipidation. However, PTV-2 infection did not enhance autophagic
      protein degradation. When cellular autophagy was pharmacologically inhibited by
      wortmannin or 3-methyladenine, PTV-2 replication increased. The increase in virus
      yield via autophagy inhibition was further confirmed by silencing atg5, which is
      required for autophagy. Furthermore, PTV-2 replication was suppressed when
      autophagy was activated by rapamycin. Together, the results suggest that PTV-2
      infection activates incomplete autophagy and that autophagy then inhibits further
      PTV-2 replication.

PMID- 29177546
TI  - Correction to: Blood lymphocyte subsets identify optimal responders to IFN-beta
      in MS.
AB  - The author claims that his name is incorrectly listed on PubMed. It seems that
      the first and last name has been mixed up.

PMID- 29177547
TI  - Genetic and clinical characteristics of hereditary transthyretin amyloidosis in
      endemic and non-endemic areas: experience from a single-referral center in Japan.
AB  - Hereditary transthyretin (ATTR) amyloidosis is a life-threatening, autosomal
      dominant, systemic amyloidosis caused by mutant transthyretin. In addition to
      ATTRV30M in endemic and non-endemic areas, more than 140 non-V30M mutations occur
      worldwide. The aim of this study was to analyze the clinical characteristics and
      genetic frequencies of hereditary ATTR amyloidosis. Diagnostic results and
      clinical manifestations of hereditary ATTR amyloidosis from April 1, 2012, to
      March 31, 2017, at Amyloidosis Medical Practice Center, Kumamoto University
      Hospital were analyzed. One hundred and four patients received a diagnosis of
      symptomatic hereditary ATTR amyloidosis. The following mutations of the TTR gene
      and their percentages were found: V30M in endemic areas, 10.6%; V30M in non
      endemic areas, 51.0%; and non-V30M, 38.5%. The ages at onset of patients with
      ATTRV30M amyloidosis in non-endemic areas (66.6 +/- 8.7 years) and those with non
      V30M ATTR amyloidosis (55.8 +/- 13.6 years) were significantly higher than those
      with ATTRV30M amyloidosis in endemic areas (37.0 +/- 12.6 years). Of patients
      with ATTRV30M amyloidosis in endemic and non-endemic areas, and non-V30M ATTR
      amyloidosis, 63.6, 66.0, and 27.5% initially presented with polyneuropathy,
      respectively. Of patients with ATTRV30M amyloidosis in endemic areas, 81.8% had a
      family history of this disease. However, a significantly smaller percentage of
      patients with ATTRV30M amyloidosis (30.0%) in non-endemic areas and non-V30M ATTR
      amyloidosis (34.0%) had a family history. Patients with ATTRV30M amyloidosis in
      non-endemic areas and patients with non-V30M ATTR amyloidosis occurred more
      frequently than previously believed, and their clinical manifestations were
      diverse.

PMID- 29177548
TI  - Pediatric Bickerstaff brainstem encephalitis: a systematic review of literature
      and case series.
AB  - OBJECTIVE: To characterize the phenotype of pediatric Bickerstaff's brainstem
      encephalitis (BBE) and evaluate prognostic features in the clinical course,
      diagnostic studies, and treatment exposures. METHODS: We systematically reviewed
      PubMed, Web of Science, and SCOPUS databases as well as medical records at the
      Lucile Packard Children's Hospital to identify cases of pediatric BBE. Inclusion
      required all of the following criteria: age <= 20 years, presence of somnolence
      or alterations in mental status at the time of presentation or developed within 7
      days of presentation, ataxia, and ophthalmoplegia. RESULTS: We reviewed 682
      manuscripts, identifying a total of 47 pediatric BBE cases. We also describe five
      previously unreported cases. The phenotype of these pediatric patients was
      similar to previously published literature. Sixty-eight percent of patients
      demonstrated positive anti-GQ1b antibody titers, yet the presence of these
      antibodies was not associated with longer times to recovery. Patients with
      neuroimaging abnormalities featured a longer median time to recovery, but this
      was not statistically significant (p = 0.124). Overall, patients treated with any
      form of immunotherapy (intravenous immunoglobulin, steroids, or plasmapheresis)
      demonstrated shorter median time to resolution of symptoms compared to supportive
      therapy, although this trend was not statistically significant (p = 0.277). Post
      hoc t tests revealed a trend towards use of immunotherapy against supportive care
      alone (p = 0.174). CONCLUSION: Our study identified clinical, radiologic, and
      treatment features that may hold prognostic value for children with BBE. The role
      of immunotherapy remains under investigation but may prove of utility with
      further, randomized controlled studies in this rare disease.

PMID- 29177549
TI  - Different infarction patterns in patients with aortic atheroma compared to those
      with cardioembolism or large artery atherosclerosis.
AB  - Aortic atheroma is a known cause of ischemic stroke. However, it is unclear
      whether ischemic stroke is caused by emboli from aortic atheroma or by
      accompanying atherosclerosis. In this study, we evaluated lesion patterns of
      patients with complex aortic plaque (CAP) to assume the underlying
      pathophysiology. Acute ischemic stroke patients who underwent transesophageal
      echocardiography were included. CAP was defined as a plaque in the proximal aorta
      >= 4 mm thick or with a mobile component. The diffusion-weighted imaging lesion
      patterns of patients with CAP were compared to those with large arterial
      atherosclerosis (LAA) or cardioembolism (CE). A total of 64 CAP patients, 127 LAA
      patients, and 80 CE patients were included. Small cortical pattern was more
      common in the CAP group (45.3%) than in the LAA (7.9%, p < 0.001) or the CE group
      (23.8%, p = 0.018). A large cortical pattern was more common in the CE group than
      in the CAP group (p < 0.001), whereas subcortical only pattern tended to be more
      common in the CAP group than in the CE group (p = 0.057). In multinominal
      analysis, the CAP group was more likely to have a small cortical lesion than the
      LAA group [odds ratio (OR) 14.63; 95% confidence interval (CI) 4.67-45.85] or the
      CE (OR 3.69, 95% CI 1.19-11.39) group. In conclusion, patients with CAP
      frequently had small cortical lesions or subcortical single lesion. These
      findings imply that ischemic stroke in aortic atheroma patients is associated
      with either small emboli or small artery disease.

PMID- 29177552
TI  - Expert's comment concerning Grand Rounds case entitled "Slow correction of severe
      spastic hyperlordosis in an adult by means of magnetically expandable rods" by C.
      Birkenmaier et al. [Eur Spine J (2017): doi:10.1007/s00586-017-5366-2].

PMID- 29177550
TI  - How to Care for Patients with EA-TEF: The Known and the Unknown.
AB  - PURPOSE OF REVIEW: Guidelines were recently published highlighting why esophageal
      atresia (EA) patients are prone to complication risks, and the need for long-term
      follow-up. In this review, we will focus on how to investigate and treat
      potential complications, as well as the pros and cons of different investigative
      and treatment modalities, and what areas continue to need further research.
      RECENT FINDINGS: EA patients are at high risk for gastroesophageal reflux and
      esophageal strictures, and the sequela that result. Extraintestinal
      manifestations of gastroesophageal reflux disease (GERD) can appear similar to
      other pathologic diagnoses commonly found in EA patients, such as congenital
      stricture, eosinophilic esophagitis, esophageal dysmotility, tracheomalacia,
      recurrent fistula, aspiration, etc. Therefore, it is important to have a
      standardized way to monitor for these issues. pH impedance allows for detection
      of nonacid reflux and the height of reflux, which are important in correlating
      symptoms with reflux episodes. A multidisciplinary approach is beneficial in
      evaluating and monitoring EA patients in the long term.

PMID- 29177553
TI  - A novel posterior approach preserving three muscles inserted at C2 in multilevel
      cervical posterior decompression and fusion using C2 pedicle screws.
AB  - PURPOSE: To present a novel posterior approach in multilevel cervical posterior
      decompression and fusion (PDF) using C2 pedicle screws that preserves the rectus
      capitis posterior major, oblique capitis inferior, and semispinalis cervicis.
      METHODS: We analyzed 30 consecutive patients who underwent C2-T1 PDF using an
      approach that preserved these three muscles without resecting. We assessed O-C2
      range of motion (ROM), cross-sectional area of the cervical posterior muscles,
      rotational ROM, visual analog scale (VAS) for axial pain, neck disability index
      (NDI), and limitations of activities of daily living (ADL) involving neck
      movements. RESULTS: Mean preoperative O-C2 ROM (23.6 degrees ) was significantly
      increased postoperatively (33.0 degrees ). Mean atrophy rate of the cross
      sectional area was 3.9%. Postoperatively, 69.8% of the preoperative rotational
      ROM (113.3 degrees ) was retained. The preoperative VAS for axial pain and the
      NDI did not increase postoperatively. The postoperative O-C2 ROM (33.9 degrees )
      in 26 patients for whom extension ADL were possible was significantly larger than
      that in four patients for whom extension ADL were impossible (26.9 degrees ). The
      postoperative retained rate of rotational ROM (75.8%) in 18 patients for whom
      rotation ADL were possible was significantly larger than that in 12 patients for
      whom rotation ADL were impossible (62.3%). CONCLUSIONS: This is potentially an
      effective approach for maintaining O-C2 ROM and rotational ROM, which enabled
      good levels of ADL after C2-T1 PDF. Axial pain and NDI were not worse after PDF.

PMID- 29177554
TI  - Description of the sagittal alignment of the degenerative human spine.
AB  - PURPOSE: To present the description of sagittal alignment of the degenerative
      human spine and its possible evolution. MATERIALS AND METHODS: This is a
      retrospective observational study of degenerative evolution in spinal alignment
      in low back pain patients. Full spine EOS(r) sagittal X-rays were analyzed, and
      pelvic and spinal parameters were measured. Spinal shapes were classified on the
      hypothesis that the possible sagittal shapes of degenerative spine would be
      divided into four categories: "classical" Roussouly types 1-4, anteverted types
      (PT <= 5), retroverted types (PT >= 25) and kyphotic types. RESULTS: A total of
      331 patients (280 women and 51 men) were included. "Classic" types 1-4
      represented the majority in this cohort (71.9%). Retroverted types made the
      second most common category with 20.8% of the cohort. Kyphosis group (lumbar and
      global) make only 5.8% of this cohort, while anteverted group make the lowest
      incidence (1.5%). Retroverted type 2 with thoracic kyphosis should be considered
      a separate type and made 1.5% of this cohort. Two theoretical subtypes,
      retroverted type 1 and type 4 were not found. CONCLUSIONS: This is the first
      description of degenerative spine disease based on its shape and based on the
      classification of the normal variation in the sagittal alignment of the human
      lumbar spine described by Roussouly. Eleven types, divided into classical types,
      anteverted types, false shapes (retroverted) and kyphotic shapes, are described
      and an evolution pathway is proposed. An evaluation of surgical results in order
      to propose a treatment algorithm based on this classification should follow.
      LEVEL OF EVIDENCE: Level IV cross sectional observational study.

PMID- 29177555
TI  - Efficacy of photodynamic therapy as adjunct treatment of chronic periodontitis: a
      systematic review and meta-analysis.
AB  - Meta-analysis of treatment effects of antimicrobial photodynamic therapy (aPDT)
      adjunct to non-surgical scaling and root planing (SRP) in comparison to SRP alone
      on patients with chronic periodontitis. The meta-analysis was performed according
      to PRISMA statement and Cochrane Collaboration guidelines. Electronic search
      complemented by hand search assured a high yield of randomized controlled trials
      (RCTs) of aPDT as adjunct modality to SRP. Differences in probing depth (PD) and
      clinical attachment level (CAL) were calculated with 95% confidence intervals and
      pooled in a random effects model. Analysis for intra- and inter-study
      heterogeneity was provided by chi 2 and I 2 tests, and publication bias was
      checked by funnel plots. Pooled overall effects of 26 RCTs attested significant
      benefits of aPDT adjunct to SRP with respect to PD reduction (MD 0.37; 95% CI
      0.12-0.53; P < 0.0001) and CAL gain (MD 0.33; 95% CI 0.19-0.48; P < 0.00001)
      after 3 and 6 months. Sensitivity analysis minimized heterogeneity of PD
      reduction (MD 0.21; 95% CI 0.13-0.30; P < 0.00001) and CAL gain (MD 0.36; 95% CI
      0.27-0.46). aPDT adjunct to SRP provides significant PD reduction and CAL gain in
      treatment of chronic periodontitis. This moderate effect was found after 3 and 6
      months which is short from a clinical perspective.

PMID- 29177558
TI  - On Applicability of Tunable Filter Bank Based Feature for Ear Biometrics: A Study
      from Constrained to Unconstrained.
AB  - In this paper, an overall framework has been presented for person verification
      using ear biometric which uses tunable filter bank as local feature extractor.
      The tunable filter bank, based on a half-band polynomial of 14th order, extracts
      distinct features from ear images maintaining its frequency selectivity property.
      To advocate the applicability of tunable filter bank on ear biometrics,
      recognition test has been performed on available constrained databases like AMI,
      WPUT, IITD and unconstrained database like UERC. Experiments have been conducted
      applying tunable filter based feature extractor on subparts of the ear. Empirical
      experiments have been conducted with four and six subdivisions of the ear image.
      Analyzing the experimental results, it has been found that tunable filter
      moderately succeeds to distinguish ear features at par with the state-of-the-art
      features used for ear recognition. Accuracies of 70.58%, 67.01%, 81.98%, and
      57.75% have been achieved on AMI, WPUT, IITD, and UERC databases through
      considering Canberra Distance as underlying measure of separation. The
      performances indicate that tunable filter is a candidate for recognizing human
      from ear images.

PMID- 29177551
TI  - Diagnosis and management of gastrointestinal complications in adult cancer
      patients: 2017 updated evidence-based guidelines of the Infectious Diseases
      Working Party (AGIHO) of the German Society of Hematology and Medical Oncology
      (DGHO).
AB  - Cancer patients frequently suffer from gastrointestinal complications. In this
      manuscript, we update our 2013 guideline on the diagnosis and management of
      gastrointestinal complications in adult cancer patients by the Infectious
      Diseases Working Party (AGIHO) of the German Society of Hematology and Medical
      Oncology (DGHO). An expert group was put together by the AGIHO to update the
      existing guideline. For each sub-topic, a literature search was performed in
      PubMed, Medline, and Cochrane databases, and strengths of recommendation and the
      quality of the published evidence for major therapeutic strategies were
      categorized using the 2015 European Society for Clinical Microbiology and
      Infectious Diseases (ESCMID) criteria. Final recommendations were approved by the
      AGIHO plenary conference. Recommendations were made with respect to non
      infectious and infectious gastrointestinal complications. Strengths of
      recommendation and levels of evidence are presented. A multidisciplinary approach
      to the diagnosis and management of gastrointestinal complications in cancer
      patients is mandatory. Evidence-based recommendations are provided in this
      updated guideline.

PMID- 29177557
TI  - Can checkpoint inhibitor therapy improve response to chemotherapy?

PMID- 29177556
TI  - Comparison of the effect of root surface modification with citric acid, EDTA, and
      aPDT on adhesion and proliferation of human gingival fibroblasts and osteoblasts:
      an in vitro study.
AB  - Root demineralization is used in Periodontics as an adjuvant for mechanical
      treatment. The aim of this study was to evaluate the effects of root surface
      modification with mechanic, chemical, and photodynamic treatments on adhesion and
      proliferation of human gingival fibroblasts and osteoblasts. Root fragments were
      treated by scaling and root planing (C-control group), EDTA (pH 7), citric acid
      plus tetracycline (CA-pH 1), and antimicrobial photodynamic therapy (aPDT) with
      toluidine blue O and red laser (pH 4). Cells were seeded (104 cells/well, 6th
      passage) on root fragments of each experimental group and cultured for 24, 48,
      and 72 h. Cells were counted in scanning electron microscopy images by a
      calibrated examiner. For fibroblasts, the highest number of cells were present at
      72-h period (p < 0.05). EDTA group showed a very low number of cells in relation
      to CA group (p < 0.05). CA and aPDT group presented higher number of cells in all
      periods, but without differences between other treatment groups (p > 0.05). For
      osteoblasts, there was a significant increase in cell numbers for aPDT group at
      72 h (p < 0.05). In conclusion, aPDT treatment provided a positive stimulus to
      osteoblast growth, while for fibroblasts, aPDT and CA had a tendency for higher
      cell growth.

PMID- 29177559
TI  - Spanish consensus on treat to target for osteoporosis.
AB  - : To reach a Spanish expert consensus on a treat-to-target strategy in
      osteoporosis, a Delphi Consensus Study has been developed. Most of the experts
      (59.8%) were rheumatologist with a mean clinical experience of 21.3 years (SD
      8.5). Consensus was achieved for 70% of the items. Therapeutic objectives,
      patient follow-up scheme, treatment failure criteria, and appropriate treatment
      choice for use in T2T strategy in Spain have been defined. INTRODUCTION: The
      paper aims to achieve a Spanish expert consensus on a treat-to-target (T2T)
      strategy in osteoporosis. METHODS: A scientific committee led the project and was
      involved in expert panel identification and Delphi questionnaire development. Two
      Delphi rounds were completed. The first-round questionnaire included 24 items and
      assessed, using a seven-point Likert scale, the experts' wish (W) and prognosis
      (P) in 5 years for each topic (applicability, therapeutic objectives, patient
      follow-up, and possible treatment to be prescribed). Items for which there was no
      consensus in the first round were included in the second round. Consensus was
      defined as >=75% agreement (somewhat/mostly/entirely agree) or disagreement
      (somewhat/mostly/entirely disagree) responses. RESULTS: Of the experts, 112 and
      106 completed the first and second rounds, respectively. 59.8% were
      rheumatologists with a mean clinical experience of 21.3 years (SD 8.5). Consensus
      was achieved for 70% of the items, and was established regarding the utility of a
      T2T strategy to define therapeutic objectives, optimal follow-up, and therapeutic
      algorithm. Participants agreed on the utility of the bone mineral density (BMD)
      value (T-score >-2.5 SD for spine and >-2.5/-2.0 SD for femoral neck), lack of
      fractures, and fracture risk (FRAX) as therapeutic objectives. For measuring BMD
      changes, consensus was achieved on the suitability of hip and femoral neck
      locations. Experts agreed to consider treatment failure as when a significant BMD
      gain could not be achieved, or when a new fracture occurs within 2-3 years. There
      was consensus that all proposed therapies should achieve a therapeutic target
      through T2T strategy (treatments with the highest consensus scores were denosumab
      and teriparatide). CONCLUSION: The therapeutic objectives, patient follow-up
      scheme, treatment failure criteria, and appropriate treatment choice for use in
      T2T strategy in Spain have been established by a panel of experts. Some aspects
      nevertheless still require further analysis.

PMID- 29177560
TI  - The Clinical Significance of Informant Agreement in Externalizing Behavior from
      Age 3 to 14.
AB  - The objective of the current study was to test to what extent agreement between
      preschool teachers (using a questionnaire-based assessment) and clinicians (using
      a clinician-rated behavioral task) with regard to externalizing problems in early
      childhood was predictive of parent reports of children's externalizing behavior
      trajectory from age 3 to age 14. The prospective longitudinal study was conducted
      over five waves with 111 clinically referred children aged 3-5 years in wave 1.
      Analyses were conducted using a multilevel modeling framework. The results of the
      conditional model testing the association of informant agreement with behavioral
      trajectories show that the greater the number of informants reporting a high
      level of behavioral problems in early childhood, the more the trajectory
      increases until adolescence. The results stress the importance of multi-informant
      assessment not only for methodological reasons but in order to target at-risk
      children.

PMID- 29177562
TI  - Toxicity and efficacy of autologous hematopoietic cell transplantation in elderly
      patients with aggressive lymphoma: a historical prospective study.
AB  - High-dose therapy followed by autologous hematopoietic cell transplantation (HCT)
      prolongs overall survival in patients under 65 years old with relapsed aggressive
      lymphoma. We aimed to explore the toxicity and efficacy of HCT in patients over
      65 years with aggressive lymphoma compared with younger patients. We compared the
      transplantation outcomes between patients >= 65 years (n = 58) and 55-64 years (n
      = 44) with chemosensitive aggressive lymphoma (DLBCL, MCL and TCL) that underwent
      HCT between 1999 and 2016 in the Tel-Aviv Medical Center. The median age was 68
      (range, 65-74) and 61 (range, 55-64) years, respectively. There were no
      differences in the incidences of grade 3-4 mucositis, documented infections and
      pulmonary complications between the two groups. There was no difference in the
      incidences of secondary malignancies, relapse (p = .26), non-relapse mortality,
      (p = .77) and overall survival (p = .53). Multivariate analysis revealed that
      smoking was a risk factor for non-relapse mortality, while partial remission and
      > 2 lines of treatment prior HCT were associated with higher risk for relapse.
      Psycho-socioeconomic score was associated with prolonged hospitalization after
      HCT and recurrent hospitalizations. We conclude that patients >= 65 years old
      with aggressive lymphoma, compared to younger counterparts, have similar
      transplantation outcome. Improving habits and psychosocial factors may further
      improve outcomes in these patients.

PMID- 29177561
TI  - How can and should we optimize extracorporeal shockwave lithotripsy?
AB  - It is well recognized that the popularity of extracorporeal shock wave
      lithotripsy (SWL), despite its non-invasive character, has decreased during
      recent years. This is partly explained by the technological achievements in
      endoscopy and urologists' enthusiasm for such procedures. Another explanation is
      that many urologists have been insufficiently successful with SWL. The latter
      effect might to some extent be a result of the performance of the lithotripter
      used, but in too many cases, it is evident that the principles of how shock wave
      lithotripsy should be carried out are poorly applied. The purpose of this article
      is to emphasize some important aspects on how SWL best should be used. Based on
      decades of experience, it stands to reason that success with SWL does not come
      automatically and attention has to be paid to all details of this technique.

PMID- 29177563
TI  - The impact of detention on the social-emotional wellbeing of children seeking
      asylum: a comparison with community-based children.
AB  - Accumulating literature demonstrates that immigration detention is harmful to
      children. However, there is a scarcity of scientifically rigorous and reliable
      data about the health of children held in detention facilities. The aim of the
      study was to compare a community-based population of recently arrived refugee
      children flown into Australia, not detained, resettled in a non-urban area, with
      a population of children who arrived by boat seeking asylum, detained since
      arrival. The parent-version of the strength and difficulties questionnaire (SDQ)
      of children aged 4-15 years was compared in children living in the community with
      those held in detention. We compared 86 children who had a parent-completed SDQ
      performed, 38 (44%) in the community group and 48 (56%) in the detention group.
      The community sample had been living in Australia for 325 days, with no time in
      detention. The detention sample had been living in detention for a mean of 221
      days. The mean age was similar for the community and detention sample at 8.4
      years (P = 0.18). In the total sample, children in the detention group had
      significantly higher SDQ total difficulties scores than children in the community
      group (P < 0.0001). There was no difference between age groups (P = 0.82). The
      children in the detention group had, on average, an SDQ total difficulties score
      that was 12 points higher than children in the community group. Four of the five
      SDQ subscale scores indicated greater disturbance amongst children in detention
      (< 0.0001) compared to children living in the community. The detention group had
      significantly higher scores (P < 0.001) for all except Pro-social scores as
      compared to Australian norms for the 4-6 and 7-15 years age group. This study
      presents a rare opportunity to compare the wellbeing of displaced children who
      were detained following arrival in Australia with those settled in the Australian
      community since arrival. The community children's scores approximated data from
      the general Australian childhood population. Children held in detention had
      significantly more social, emotional and behavioural difficulties than children
      living in the community, and at levels resembling a clinical cohort. Despite the
      small sample size, data restrictions and other limitations of the data,
      statistical significance in differences between the community and detention
      children is marked and arguably demonstrates the negative impact of post-arrival
      detention in children who are presumed to have similar levels of pre-arrival
      adversity. If the objective is to optimise the health and wellbeing of children
      seeking asylum, removal of post-arrival detention is one of the most powerful
      interventions available to host countries.

PMID- 29177564
TI  - Trajectories of mental health problems in children of parents with mental health
      problems: results of the BELLA study.
AB  - Children of parents with mental health problems (CPM) have an increased risk for
      behavioral and psychological problems. This study investigated the age- and
      gender-specific course as well as predictors of mental health problems in CPM
      using the longitudinal data (baseline 1- and 2-year follow-ups) of a German
      general population sample from the BELLA study. Children and adolescents aged 11
      17 years (at baseline) who had a parent with mental health problems (n = 325)
      were analyzed. The mental health problems of the children were assessed by the
      self-reported version of the strengths and difficulties questionnaire (SDQ). We
      used individual growth modeling to investigate the age- and gender-specific
      course, and the effects of risk as well as personal, familial and social
      protective factors on self-reported mental health problems in CPM. Additionally,
      data were examined differentiating internalizing and externalizing mental health
      problems in CPM. Results indicated that female compared to male CPM showed
      increasing mental health problems with increasing age. Mental health problems in
      CPM were associated with lower self-efficacy, worse family climate and less
      social competence over time. Internalizing problems were associated with lower
      self-efficacy, less social competence and more severe parental mental health
      problems. Externalizing problems were associated with lower self-efficacy, worse
      family climate and lower social competence. The main limitations of the study are
      the short time period (2 years) covered and the report of mental health problems
      by only one parent. Our findings should be considered in the development of
      treatment and prevention programs for mental health problems in CPM.

PMID- 29177566
TI  - Introduction to special section: measuring what matters.

PMID- 29177565
TI  - Breastfeeding and externalising problems: a quasi-experimental design with a
      national cohort.
AB  - Evidence from correlational studies supporting the benefits of breastfeeding on
      children's externalising problems is mixed. Quasi-experimental approaches can
      help in better understanding possible 'effects'. We aimed to investigate the
      longitudinal impact of breastfeeding on externalising problems from childhood
      into adolescence. Participants included ~ 5000 full-term children, from the
      Growing Up in Ireland Child Cohort. Externalising problems (conduct problems and
      hyperactivity) were assessed using both the parent and teacher versions of the
      Strengths and Difficulties Questionnaire when children were age 9 and 13.
      Maternal reports were used to collect retrospective information on breastfeeding.
      Propensity score matching, and adjusting for multiple testing were used to
      compare the average treatment effects for children who were breastfed. Post
      matching results revealed statistically significant reductions in hyperactivity
      at age nine, using both maternal and teacher reports (difference score - 0.48,
      95% CI - 0.85, - 0.11; and - 0.51, 95% CI - 0.90, - 0.12, respectively), for
      children who were breastfed between 6 and 12 months, but not thereafter. These
      effects were not maintained at age 13. Moreover, no effects of breastfeeding on
      conduct problems were found at any age, regardless of duration, using either
      maternal or teacher report. While some benefits of breastfeeding were found,
      compatible with a temporary modest reduction in hyperactivity, related to being
      breastfed for 26-50 weeks, these results must be viewed in the context of
      reliance of propensity score matching on observable characteristics.
      Additionally, our results are suggestive of a potential non-linear dose-response
      of breastfeeding on hyperactivity.

PMID- 29177567
TI  - Mediterranean diet and cardiovascular disease: a systematic review and meta
      analysis of observational studies.
AB  - PURPOSE: To provide evidence of the relationship of Mediterranean diet (MD) on
      incidence/mortality for cardiovascular disease (CVD), coronary/ischemic heart
      disease (CHD)/acute myocardial infarction (AMI) and stroke (ischemic/hemorrhagic)
      by sex, geographic region, study design and type of MD score (MDS). METHODS: We
      performed a systematic review and meta-analysis of observational studies. Pooled
      relative risks (RRs) were calculated using random-effects models. RESULTS: We
      identified 29 articles. The RR for the highest versus the lowest category of the
      MDS was 0.81 (95% CI 0.74-0.88) for the 11 studies that considered unspecified
      CVD, consistent across all strata. The corresponding pooled RR for CHD/AMI risk
      was 0.70 (95% CI 0.62-0.80), based on 11 studies. The inverse relationship was
      consistent across strata of study design, end point (incidence and mortality),
      sex, geographic area, and the MDS used. The overall RR for the six studies that
      considered unspecified stroke was 0.73 (95% CI 0.59-0.91) for the highest versus
      the lowest category of the MDS. The corresponding values were 0.82 (95% CI 0.73
      0.92) for ischemic (five studies) and 1.01 (95% CI 0.74-1.37) for hemorrhagic
      stroke (four studies). CONCLUSIONS: Our findings indicate and further quantify
      that MD exerts a protective effect on the risk of CVD. This inverse association
      includes CHD and ischemic stroke, but apparently not hemorrhagic stroke.

PMID- 29177568
TI  - Tachon Syndrome: Rare Side Effect of Articular Injections of Corticosteroids. A
      Report of Two Cases.
AB  - Epidural or intra-articular injections of corticosteroids are an option for the
      treatment of several pain conditions but are not without adverse effects. Here,
      we discuss a rare systemic side effect of this therapy: Tachon syndrome. We
      report two cases, a 64-year-old woman and a 43-year-old man, who presented with
      Tachon syndrome after receiving, respectively, a shoulder and a lumbar injection
      of cortivazol 3.75 mg/1.5 ml suspension for injection in pre-filled syringes. The
      indication for this therapy was, respectively, tendinopathy of the supraspinatus
      and a mechanical L5 lumbosciatica. A few minutes after receiving the injection,
      patients experienced acute low back pain, chest tightness, facial erythema and
      profuse sweating. All vital and biologic parameters were normal. In the first
      case, improvement was spontaneous and all symptoms resolved in 20 min. The second
      patient remained under observation and received an intravenous 'physiological'
      infusion. Both patients recovered fully and returned home. A causal relationship
      between the corticosteroid injections and the patients' symptoms was very likely
      because of the acute clinical presentation and the rapid improvement in the
      patients' conditions and that no further signs indicating other serious
      complications developed.

PMID- 29177569
TI  - Low Arid1a Expression Correlates with Poor Prognosis and Promotes Cell
      Proliferation and Metastasis in Osteosarcoma.
AB  - AT-rich interactive domain-containing protein 1A (ARID1A) has been shown to
      function as a tumour suppressor in various malignancies. However, the biological
      role of ARID1A in osteosarcoma is not clear. The present study aimed to
      investigate the expression pattern, prognostic value and the biological role of
      ARID1A in human osteosarcoma. ARID1A expression in 53 osteosarcoma surgical
      specimens was examined by quantitative real-time polymerase chain reaction, and
      its clinical significance was analysed. The role of ARID1A in cell proliferation,
      apoptosis, and metastasis were examined. ARID1A mRNA expression were
      significantly down-regulated in osteosarcoma tumours from that in matched
      adjacent non-tumour tissues. ARID1A expression was significantly inversely
      correlated with tumour stage and distant metastasis, as well as poor overall
      survival in patients with osteosarcoma. Furthermore, ARID1A mRNA was down
      regulated in four human osteosarcoma cell lines MG-63, U2OS, HOS and Saos-2.
      Restoring of ARID1A expression in MG-63 and U2OS cells significantly inhibited
      cell proliferation and metastasis in vitro. Collectively, our data demonstrate
      that ARID1A may serve as a tumour suppressor in osteosarcoma progression, and
      represent a valuable prognostic marker and potential therapeutic target for
      osteosarcoma.

PMID- 29177571
TI  - The case of the inside-out J-pouch: an incarcerated, prolapsed ileal pouch.

PMID- 29177570
TI  - Genetic risk factors for chemotherapy-induced nausea and vomiting in patients
      with cancer receiving cisplatin-based chemotherapy.
AB  - PURPOSE: Younger age and female sex have already been well-known risk factors for
      chemotherapy-induced nausea and vomiting (CINV), and 30-50% of cancer patients
      still suffer from CINV. Genetic polymorphisms are suggested to influence
      antiemetic treatment response. METHODS: This study included a subset of patients
      previously enrolled in a randomised controlled trial; 156 patients were
      evaluated. This study aimed to evaluate the role of pharmacogenomic polymorphisms
      relevant to antiemetic response in patients with cancer receiving cisplatin-based
      chemotherapy. The study's efficacy endpoint was the proportion of patients with
      complete response (CR). The study endpoint was evaluated separately in the acute
      (CR0-24) and delayed (CR24-120) phases. Thirteen polymorphisms were genotyped,
      and the association of these genotypes with the efficacy of prophylactic
      antiemetics was then investigated. Confounding variables for the CR were
      identified using stepwise multivariate logistic regression analysis. Age and sex
      were included as independent variables by the forced-entry method, and the
      stepwise method was used to select the pharmacogenomic factors for inclusion as
      independent variables. RESULTS: Multivariate logistic regression analysis
      revealed that the ERCC1 8092AA (odds ratio [OR] = 11.25; 95% confidence interval
      [CI] 1.74-72.71; p = 0.011) and female sex (OR = 3.63; 95% CI 1.14-11.58; p =
      0.029) were significant predictors of CR0-24. No significant association of CR24
      120 with pharmacogenomic polymorphisms was found via multivariate logistic
      regression analysis. CONCLUSIONS: ERCC1 polymorphism influenced the extent of
      CINV control in patients receiving cisplatin-based chemotherapy. TRIAL
      REGISTRATION: Clinical trial information: UMIN 000009335.

PMID- 29177572
TI  - Aripiprazole Lauroxil: A Review in Schizophrenia.
AB  - Aripiprazole lauroxil long-acting injectable (LAI) [Aristada(r)] is an
      intramuscularly administered, extended-release prodrug of aripiprazole, an
      established atypical antipsychotic agent that, in terms of its relative position
      within the class, is at the low end of the risk spectrum for metabolic side
      effects. In the USA, aripiprazole lauroxil LAI is indicated for the treatment of
      schizophrenia; approved doses of the drug can be injected once-monthly (q4w),
      every 6 weeks (q6w) or every 2 months (q8w). The efficacy of the 441 and 882 mg
      q4w dosages in the treatment of acute exacerbations of schizophrenia and as long
      term maintenance therapy in stable schizophrenia has been directly demonstrated
      in a phase III clinical trial and extension, while the efficacy of the 662 mg
      q4w, 882 mg q6w and 1064 mg q8w dosing regimens has been established on the basis
      of pharmacokinetic bridging studies. Aripiprazole lauroxil LAI therapy was
      generally well tolerated, with an adverse event profile consistent with that of
      oral aripiprazole (with the exception of injection-site reactions), including a
      low propensity to cause metabolic disturbances. Thus, aripiprazole lauroxil LAI
      extends the treatment regimen options for patients with schizophrenia; as with
      other LAI formulations of antipsychotic agents, it can be particularly
      recommended for patients with recurrent relapses related to nonadherence to oral
      preparations and for those who prefer this mode of administration. Moreover,
      unlike aripiprazole monohydrate LAI, the only other commercially available long
      acting formulation of aripiprazole, aripiprazole lauroxil LAI offers more than
      one dosing interval option, which may be a potential advantage in terms of
      tailoring therapy to the needs of individual patients.

PMID- 29177573
TI  - Triptorelin: A Review of its Use as an Adjuvant Anticancer Therapy in Early
      Breast Cancer.
AB  - A 1-month formulation of the gonadotrophin-releasing hormone agonist (GnRHa)
      triptorelin (Decapeptyl(r)) has been approved in the EU as an adjuvant treatment
      in combination with tamoxifen or an aromatase inhibitor (AI), of endocrine
      responsive, early-stage breast cancer in women at high risk of recurrence who are
      confirmed as premenopausal after completion of chemotherapy. This indication
      reflects the results of the 5-year SOFT and TEXT studies, especially SOFT, in
      which ovarian function suppression (OFS; mainly achieved with triptorelin) added
      to tamoxifen provided a significant benefit in the overall study population of
      premenopausal patients only after adjusting for prognostic factors. It emerged
      that adding OFS to tamoxifen produced more pronounced benefits in terms of
      disease control and, furthermore, increased overall survival in the cohort of
      higher-risk patients who had previously received chemotherapy. Also, compared
      with tamoxifen alone, the combination of OFS plus exemestane produced more
      pronounced benefits in terms of disease control than OFS plus tamoxifen. OFS
      induces premature menopause; when combined with either tamoxifen or exemestane,
      it increased the endocrine symptom burden. Nonetheless, the two combinations had
      distinct tolerability profiles (e.g. vasomotor symptoms and thromboembolic events
      were more frequent with OFS plus tamoxifen, whereas musculoskeletal symptoms,
      decreased libido, osteoporosis and fractures were more frequent with OFS plus
      exemestane). Thus, the combinations of OFS (with triptorelin) plus either
      tamoxifen or an AI are valid options for the adjuvant treatment of endocrine
      responsive, early-stage breast cancer in women at sufficiently high risk of
      relapse to warrant receiving chemotherapy and who remain premenopausal
      thereafter. Individualized weighing of the potential benefits and adverse effects
      of treatment is required.

PMID- 29177575
TI  - Association between sarcoidosis, pulse wave velocity, and other measures of
      subclinical atherosclerosis: a systematic review and meta-analysis.
AB  - Chronic inflammation from autoimmune diseases has shown to be a risk factor for
      atherosclerosis, subsequently leading to cardiovascular disease. Endothelial
      dysfunction is the early pathogenesis of atherosclerosis in chronic inflammation,
      but the risk of atherosclerosis in sarcoidosis is less well defined. This meta
      analysis aimed to explore the association of subclinical atherosclerosis and
      arterial stiffness in sarcoidosis. A comprehensive search of the MEDLINE and
      EMBASE databases was performed from date of inception through August 2017. The
      inclusion criterion was observational studies evaluating the association between
      sarcoidosis, subclinical atherosclerosis, and arterial stiffness by measuring
      pulse wave velocity (PWV). Definitions of sarcoidosis and methods to assess PWV
      were recorded for each study. The pooled standardized mean difference (SMD) of
      PWV and 95% confidence interval (CI) was calculated using a random-effects meta
      analysis. The between-study heterogeneity of effect size was quantified using the
      Q statistic and I 2 . Data were extracted from five observational studies
      involving 499 subjects. Pooled result demonstrated a significant increase in PWV
      in patients who have sarcoidosis compared with controls (SMD = 0.57 m/s; 95% CI
      0.21-0.92, p value = 0.002, I 2  = 75%, P heterogeneity < 0.01). After excluding
      studies with low or moderate quality, there was an increase in PWV in sarcoidosis
      compared with controls (SMD = 0.29 m/s; 95% CI 0.00-0.57, p value = 0.05, I 2  =
      55%, P heterogeneity = 0.08). Our study suggests that sarcoidosis is associated
      with increased arterial stiffness and therefore at risk of subclinical
      atherosclerosis. Prospective study is required to investigate the association of
      subclinical atherosclerosis causing overt cardiovascular disease in patients with
      sarcoidosis.

PMID- 29177574
TI  - Prevalence of psychological disorders, sleep disturbance and stressful life
      events and their relationships with disease parameters in Chinese patients with
      ankylosing spondylitis.
AB  - Our aim was to investigate the prevalence of psychological disorders, sleep
      disturbance, and stressful life events in Chinese patients with ankylosing
      spondylitis (AS) and healthy controls, to assess the correlation between
      psychological and disease-related variables, and finally to detect powerful
      factors in predicting anxiety and depression. AS patients diagnosed with the
      modified New York criteria and healthy controls were enrolled from China.
      Participants completed a set of questionnaires, including demographic and disease
      parameters, Zung self-rating anxiety scale (SAS), Zung self-rating depression
      scale (SDS), the Pittsburgh Sleep Quality Index questionnaire (PSQI), and the
      Social Readjustment Rating Scale (SRRS). The relationship between psychological
      and other variables was explored. Stepwise multiple regression was used to
      determine the contributors to each disorder. Of all the 2772 AS patients, 79.1%
      were male. Mean age was 28.99 +/- 8.87 years. Prevalence of anxiety, depression,
      and sleep disturbance was 31.6% (95% CI, 29.9, to 33.4), 59.3% (95% CI, 57.5, to
      61.2), and 31.0% (95% CI, 29.3, to 36.7), respectively. 35.3% had stimulus of
      psychological and social elements (SPSE). Compared with healthy controls, AS
      patients had more severe psychological disorders, sleep disturbance, and
      stressful life events (P < 0.01). SDS, overall pain, BASFI, and sleep disturbance
      were significant contributors of the SAS scores (P < 0.03). SAS, less years of
      education, and sleep duration were significant contributors of SDS (P < 0.01). AS
      patients had more anxiety, depression, stressful life events, and sleep
      disturbance than healthy controls. Pain, functional limitation, sleep
      disturbance, and education were major contributors to psychological disorders.

PMID- 29177576
TI  - Variation in biochemical constituents and master elements in common seaweeds from
      Alexandria Coast, Egypt, with special reference to their antioxidant activity and
      potential food uses: prospective equations.
AB  - Biochemical constituents and master elements (Pb, Cr, Cd, Fe, Cu, Zn, Hg, B, Al,
      SO42-, Na, K, Li, Ca, Mg, and F) were investigated in six different seaweed
      species from Abu Qir Bay in the Egyptian Mediterranean Sea coast. The moisture
      level ranged from 30.26% in Corallina mediterranea to 77.57% in Padina boryana.
      On dry weight basis, the ash contents varied from 25.53% in Jania rubens to
      88.84% in Sargassum wightii. The protein contents fluctuated from 8.26% in S.
      wightii to 28.01% in J. rubens. Enteromorpha linza showed the highest lipids
      (4.66%) and carbohydrate contents (78.95%), whereas C. mediterranea had the
      lowest lipid (0.5%), and carbohydrate contents (38.12%). Chlorophylls and
      carotenoid contents varied among the species. Total antioxidant capacity of the
      tested green seaweeds had the highest activities followed by brown and red
      seaweeds which had a similar trend of phenol and tannins contents. High reducing
      power was observed in all tested seaweeds extract except Ulva lactuca. Brown
      species had the highest amount of elements followed by red and green seaweeds.
      Notably, SO42- recorded the highest level in the tested green species (108.05
      mg/g dry weight (DW)). The Ca/Mg and K/Na ratios reflected highly significant
      difference between seaweed species. This study keeps an eye on 29 parameters and
      by applying stepwise multiple regression analysis, prospective equations have
      been set to describe the interactions between these parameters inside seaweeds.
      Accordingly, the tested seaweeds can be recommended as a source of healthy food
      with suitable ion quotient and estimated daily intake values.

PMID- 29177577
TI  - Enhanced performance of a novel anodic PdAu/VGCNF catalyst for electro-oxidation
      in a glycerol fuel cell.
AB  - This study presents a novel anodic PdAu/VGCNF catalyst for electro-oxidation in a
      glycerol fuel cell. The reaction conditions are critical issues affecting the
      glycerol electro-oxidation performance. This study presents the effects of
      catalyst loading, temperature, and electrolyte concentration. The glycerol
      oxidation performance of the PdAu/VGCNF catalyst on the anode side is tested via
      cyclic voltammetry with a 3 mm2 active area. The morphology and physical
      properties of the catalyst are examined using X-ray diffraction (XRD), field
      emission scanning electron microscopy (SEM) and energy dispersive X-ray (EDX)
      spectroscopy. Then, optimization is carried out using the response surface method
      with central composite experimental design. The current density is experimentally
      obtained as a response variable from a set of experimental laboratory tests. The
      catalyst loading, temperature, and NaOH concentration are taken as independent
      parameters, which were evaluated previously in the screening experiments. The
      highest current density of 158.34 mAcm-2 is obtained under the optimal conditions
      of 3.0 M NaOH concentration, 60  degrees C temperature and 12 wt.% catalyst
      loading. These results prove that PdAu-VGCNF is a potential anodic catalyst for
      glycerol fuel cells.

PMID- 29177578
TI  - Abnormalities of Lipoprotein Levels in Liver Cirrhosis: Clinical Relevance.
AB  - Progressive lipoprotein impairment occurs in liver cirrhosis and is associated
      with increased morbidity and mortality. The present review aims to summarize the
      current evidence regarding the prognostic value of lipoprotein abnormalities in
      liver cirrhosis and to address the need of a better prognostic stratification of
      patients, including lipoprotein profile assessment. Low levels of lipoproteins
      are usual in cirrhosis. Much evidence supports the prognostic role of
      hypolipidemia in cirrhotic patients. In particular, hypocholesterolemia
      represents an independent predictor of survival in cirrhosis. In cirrhotic
      patients, lipoprotein impairment is associated with several complications:
      infections, malnutrition, adrenal function, and spur cell anemia. Alterations of
      liver function are associated with modifications of circulating lipids. Decreased
      levels of lipoproteins significantly impact the survival of cirrhotic patients
      and play an important role in the pathogenesis of some cirrhosis-related
      complications.

PMID- 29177579
TI  - Disagreement between splenic switch-off and myocardial T1-mapping after caffeine
      intake.
AB  - Caffeine is an adenosine receptor antagonist and a possible cause of inadequate
      stress perfusion. Splenic switch-off (SSO) and splenic rest-stress T1-mapping
      have been proposed as indicators of stress adequacy during perfusion cardiac
      magnetic resonance (CMR). We compared myocardial rest-stress T1-mapping with SSO
      and splenic rest-stress T1-mapping in patients with and without recent coffee
      intake. We analyzed 344 consecutive patients suspected of myocardial ischemia
      with adenosine perfusion CMR. All 146 normal CMR studies with a normal T1-rest of
      the myocardium, used as standard of reference, were included and divided in two
      groups. 22 patients accidentally ingested coffee < 4 h before CMR, compared to
      control group of 124 patients without self-reported coffee intake. Two
      independent readers graded SSO visually. T1-reactivity (DeltaT1) was defined as
      percentual difference in T1-rest and T1-stress. Follow-up data were extracted
      from electronic patients records. In patients with recent coffee intake SSO was
      identified in 96%, which showed no significant difference with SSO in controls
      (94%, p = 0.835), however event rates were significantly different (13.6 and
      0.8%, respectively (p < 0.001), median FU 17 months). Myocardial DeltaT1 in the
      coffee group (- 5.2%) was significantly lower compared to control (+ 4.0%, p <
      0.001), in contrast to the splenic DeltaT1 (- 3.7 and - 4.0%, p = 0.789). The
      splenic T1-mapping results failed to predict false negative results. SSO and
      splenic rest-stress T1-mapping are not reliable indicators of stress adequacy in
      patients with recent coffee intake. Therefore, the dark spleen sign does not
      indicate adequate myocardial stress in patients with recent caffeine intake.
      Myocardial rest-stress T1-mapping is an excellent indicator of stress adequacy
      during adenosine perfusion CMR.

PMID- 29177580
TI  - Molecular detection and genetic characterizations of Cryptosporidium spp. in
      farmed foxes, minks, and raccoon dogs in northeastern China.
AB  - Cryptosporidium spp. are common intestinal protozoa causing diarrhea in humans
      and a variety of animal species. With the recent development of fur industry, a
      large number of fur animals are farmed worldwide, especially in China. The
      existence of identical Cryptosporidium species/genotypes in humans and fur
      animals suggests zoonotic potential. In order to assess the presence of zoonotic
      Cryptosporidium species and/or genotypes in farmed fur animals, 367 fecal
      specimens were collected from 213 foxes, 114 minks and 40 raccoon dogs farmed in
      Heilongjiang, Jilin, and Liaoning provinces, northeastern China, during the
      period from June 2014 to October 2016. By PCR and sequencing of the partial small
      subunit (SSU) rRNA gene of Cryptosporidium, 20 of 367 (5.4%) animal samples were
      found to be infected, corresponding to 12 of 213 fox samples (5.6%) and 8 of 114
      mink samples (7.0%) screened. Three Cryptosporidium species/genotypes were
      identified: C. canis (n = 17), C. meleagridis (n = 1) and Cryptosporidium mink
      genotype (n = 2). Two host-adapted C. canis types (C. canis dog genotype and C.
      canis fox genotype) were found. By PCR and sequencing of the partial 60 kDa
      glycoprotein (gp60) encoding gene, one mink genotype isolate was successfully
      subtyped as XcA5G1R1. The three Cryptosporidium species/genotypes identified in
      this study have been previously reported in humans suggesting that fur animals
      infected with Cryptosporidium spp. may pose a risk of zoonotic transmission of
      cryptosporidiosis, especially for the people working in fur animal farming and
      processing industry.

PMID- 29177581
TI  - An apparent Acanthamoeba genotype is the product of a chimeric 18S rDNA artifact.
AB  - Free-living amoebae of the genus Acanthamoeba are potentially pathogenic protozoa
      widespread in the environment. The detection/diagnosis as well as environmental
      survey strategies is mainly based on the identification of the 18S rDNA sequences
      of the strains that allow the recovery of various distinct
      genotypes/subgenotypes. The accurate recording of such data is important to
      better know the environmental distribution of distinct genotypes and how they may
      be preferentially associated with disease. Recently, a putative new acanthamoebal
      genotype T99 was introduced, which comprises only environmental clones apparently
      with some anomalous features. Here, we analyze these sequences through partial
      treeing and BLAST analyses and find that they are actually chimeras. Our results
      show that the putative T99 genotype is very likely formed by chimeric sequences
      including a middle fragment from acanthamoebae of genotype T13, while the 5'- and
      3'-end fragments came from a nematode and a cercozoan, respectively. Molecular
      phylogenies of Acanthamoeba including T99 are consequently erroneous as genotype
      T99 does not exist in nature. Careful identification of Acanthamoeba genotypes is
      therefore critical for both phylogenetic and diagnostic applications.

PMID- 29177582
TI  - The invasive cestode parasite Ligula from salmonids and bullies on the South
      Island, New Zealand.
AB  - Freshwater ecosystems are often impacted by biological invasions, including the
      introduction of exotic parasites capable of infecting native species. Here, we
      report the occurrence of the introduced tapeworm Ligula sp. from common bully,
      Gobiomorphus cotidianus, and quinnat salmon, Oncorhynchus tshawytscha, in Lake
      Hawea, South Island, New Zealand. This parasite has a complex life cycle,
      reaching its adult stage in fish-eating birds. Worms recovered from the body
      cavity of fish hosts reached huge sizes (60-300 mm long); however, their low
      prevalence in fish populations suggests that infections are rare or localised.
      Molecular analysis (internal transcribed spacer (ITS)1 and ITS2 sequences)
      confirms that these specimens belong to the genus Ligula and suggests tentative
      routes of invasion into New Zealand. Monitoring the spread of this parasite is
      important, as it can impact fish populations and also, when infection levels are
      high, those of piscivorous birds.

PMID- 29177583
TI  - Identification and functional analysis of the novel ORF6 protein of porcine
      circovirus type 2 in vitro.
AB  - In the present study, the function of a novel ORF6 gene in the PCV2 genome was
      determined and functionally analyzed in vitro. ORF6 expression was demonstrated
      by indirect immunofluorescence in PCV2-infected cells. The antibody against ORF6
      was detected in PCV2-infected pigs. The start codon of ORF6 was mutated and an
      infectious clone was used to create an ORF6-deficient mutant virus. Viral DNA
      replication curves and immunofluorescence analysis indicated that ORF6 is
      unnecessary for viral replication and ORF6 deletion reduces viral DNA replication
      in PK-15 cells. The activities of caspases 3 and 8 in ORF6-deficient virus
      infected cells were significantly different from those in wild-type virus
      infected cells. The ORF6 protein can increase the expression of IFN-beta, TNF
      alpha, IL-1b, IL-10, and IL-12p40. These results demonstrated that the newly
      discovered ORF6 protein may be involved in caspases regulation and the expression
      of multiple cytokines in PCV2-infected cells. The functions of this gene in viral
      pathogenesis remain to be further elucidated.

PMID- 29177584
TI  - Sirtuin 6, a possible therapeutic target for type 2 diabetes.
AB  - Sirtuin 6 (SIRT6), one of the seven members of mammalian sirtuin family,
      localizes in the nucleus and primarily regulates chromatin signaling and genomic
      integrity. Recent studies established the critical role of SIRT6 in the
      pathophysiology of metabolic disease, as well as its roles in longevity and
      cancer. These roles that were determined by genetic studies include promoting
      pancreatic insulin secretion, inhibiting hepatic gluconeogenesis and triglyceride
      synthesis, and suppressing adiposity, suggesting that SIRT6 activators are
      promising molecules for treating obesity and diabetes. In contrast, a recent
      study showed that a synthetic inhibitor of SIRT6 improved glucose tolerance in a
      type 2 diabetes mouse model, associated with increased glycolysis and the
      expression of glucose transporter GLUT-1 and 4 in skeletal muscle, providing
      proof-of-concept evidence of SIRT6 inhibition as a treatment for diabetes. This
      review summarizes the confounding findings on the role of SIRT6 in metabolic
      homeostasis and discusses the possible relationships of these findings as they
      relate to the use of SIRT6 as a therapeutic target for type 2 diabetes and
      related diseases.

PMID- 29177585
TI  - The role of exercise-induced myokines in regulating metabolism.
AB  - Exercise has beneficial effects in ameliorating metabolic disorders, and a
      combined therapeutic regimen of regular exercise and pharmaceutical treatment is
      often recommended. Exercise biology is complex and it involves various metabolic
      and molecular changes that translate into changes in substrate utilization,
      enzyme activation, and alternatively, improvement in exercise performance.
      Besides the effect of exercise on muscle metabolism, it has recently been
      discovered that contracting muscle can induce secretion of molecules called
      myokines. In the past few decades, a number of myokines have been discovered,
      such as interleukin-6, irisin, myostatin, interleukin-15, brain-derived
      neurotrophic factor, beta-aminoisobutyric acid, meteorin-like, leukemia
      inhibitory factor, and secreted protein acidic and rich in cysteine, through
      secretome analysis. The existence of myokines has enhanced our understanding of
      how muscles communicate with other organs such as adipose tissue, liver, bone,
      and brain to exert beneficial effects of exercise at the whole body level. In
      this review, we focus on the role of these myokines in regulating local muscle
      metabolism as well as systemic metabolism in an autocrine/paracrine/endocrine
      fashion. The therapeutic potential of myokines and the natural or synthetic
      compounds known to date that regulate myokines are also discussed.

PMID- 29177586
TI  - Phenolic amides from Tribulus terrestris and their inhibitory effects on nitric
      oxide production in RAW 264.7 cells.
AB  - A new phenolic amide, named cis-terrestriamide (7), together with ten known
      compounds (1-6, 8-11), were isolated from the methanolic extract of the fruits of
      Tribulus terrestris. The structure of 7 was elucidated on the basis of extensive
      analyses of 1D and 2D nuclear magnetic resonance spectroscopic and high
      resolution mass spectrometry data. Compounds 1, 2, 5, 6, 8, 9, and 11 exhibited
      inhibitory effects on the lipopolysaccharide-stimulated nitric oxide production
      in RAW 264.7 cells, with IC50 values of 18.7-49.4 MUM.

PMID- 29177589
TI  - Ultrasound guided core needle biopsy prior to thermo ablative treatment of
      uterine tumors: first results.
AB  - PURPOSE: This study aimed at evaluating the diagnostic yield for core needle
      biopsies of uterine fibroids before laparoscopic radiofrequency volumetric
      thermal ablation (RFVTA) with the aim of sonographic imaging. This study was in
      the context of a randomized, prospective, single-center, longitudinal comparative
      study in which RFVTA and laparoscopic myomectomy for symptomatic uterine fibroids
      were compared. METHODS: All patients of the RFVTA-arm received a core needle
      biopsy under the guidance of an intraoperative laparoscopic ultrasound system.
      The Tissue samples were observed histologically. RESULTS: 24 patients were
      included and received in the median 3.17 biopsies (range 2-7). 45.8% of the
      fibroids were intramural. In 92% uterine leiomyoma was detected, in 4% a cell
      rich leiomyoma and in 4% a smooth muscle tumor with uncertain malignant potential
      (STUMP). There were no complications caused by core needle biopsy. CONCLUSIONS:
      Ultrasound guided core needle biopsy can be used to receive a histological result
      before treating uterine fibroids with thermo surgical methods like RFVTA.

PMID- 29177587
TI  - Intranasal Therapy to Stop Status Epilepticus in Prehospital Settings.
AB  - Status epilepticus (SE) is a medical emergency characterized by uncontrolled,
      prolonged seizures with rapid and widespread neuronal damage. Patients that
      suffer from longer episodes of SE are more likely to have poorer clinical
      outcomes and a higher cost of healthcare. Understanding novel molecular
      mechanisms that regulate inhibitory and excitatory neurotransmission that
      initiate SE and the necessary medical infrastructure to stop SE could help
      identify targets for early intervention. Intranasal administration of
      benzodiazepines may shorten the time between initiation and cessation of seizures
      when compared to other routes of administration. Current pharmaceutical
      administration guidelines are appropriate for sporadic incidences of SE, but
      exploring other approaches is necessary to prepare for situations involving
      multiple patients outside of a hospital, such as a massive chemical weapons
      attack. Intranasal drug delivery helps to circumvent the blood-brain barrier and
      offers a noninvasive way to quickly administer drugs in settings that require an
      immediate response, such as nerve agent exposure. In addition, examining the
      intranasal delivery of new drugs, such as nanotherapeutics, may lead to more
      effective, noninvasive, scalable, and portable methods of treating SE.

PMID- 29177588
TI  - Treatment of giant paraesophageal hernia: pro laparoscopic approach.
AB  - PURPOSE: Giant paraesophageal hernias (GPEH) are relatively uncommon and account
      for less than 5% of all primary hiatal hernias. Giant Secondary GPEH can be
      observed after surgery involving hiatal orifice opening, such as esophagectomy,
      antireflux surgery, and hiatal hernia repair. Surgical treatment is challenging,
      and there are still residual controversies regarding the laparoscopic approach,
      even though a reduced morbidity and mortality, as well as a shorter hospital stay
      have been demonstrated. METHODS: A Pubmed electronic search of the literature
      including articles published between 1992 and 2016 was conducted using the
      following key words: hiatal hernia, paraesophageal hernias, mesh, laparoscopy,
      intrathoracic stomach, gastric volvulus, diaphragmatic hernia. RESULTS: Given the
      risks of non-operative management, GPEH surgical repair is indicated in
      symptomatic patients. Technical steps for primary hernia repair include hernia
      reduction and sac excision, correct repositioning of the gastroesophageal
      junction, crural repair, and fundoplication. For secondary hernias, the surgical
      technique varies according to hernia type and components and according to the
      approach used during the first surgery. There is an ongoing debate regarding the
      best and safest method to close the hiatal orifice. The laparoscopic approach has
      demonstrated a lower postoperative morbidity and mortality, and a shorter
      hospital stay as compared to the open approach. A high recurrence rate has been
      reported for primary GPEH repair. However, recent studies suggest that recurrence
      does not reduce symptomatic outcomes. CONCLUSIONS: The laparoscopic treatment of
      primary and secondary GPEH is safe and feasible in elective and emergency
      settings, especially in high-volume centers. The procedure is still challenging.
      The main steps are well defined. However, there is still room for improvement to
      lower the recurrence rate.

PMID- 29177590
TI  - Risk of parametrial invasion in women with early stage cervical cancer: a meta
      analysis.
AB  - PURPOSE: To first evaluate the predictive value of lymph-vascular space invasion
      (LVSI) and pelvic lymph node metastases (LNM) to parametrial invasion (PI) in
      patients with early stage cervical cancer. METHODS: A systematic search of
      electronic databases was conducted to identify publications exploring the
      association between LVSI, LNM, and PI. The following databases were searched:
      PubMed/Medline and Web of Science. Twenty relevant studies were included. Pooling
      of results was done based on these studies and a diagnostic meta-analysis was
      performed. RESULTS: 20 articles and a total of 7373 cases were included in the
      meta-analysis. 17 studies analyzed the correlation between LVSI and PI and 18
      studies evaluated the correlation between LNM and PI. The existence of LVSI
      accelerated PI with OR being 7.37 (95% CI 5.70-9.54) in fixed-effect model and
      7.32 (95% CI 4.65-10.39) in random effects model. LVSI shows high sensitivity of
      0.80 and the AUC was 0.82. The existence of LNM accelerated PI. LNM shows the
      highest specificity of 0.90 and the AUC was 0.77. CONCLUSIONS: Both LVSI and LNM
      are associated with PI. Conization and lymphadenectomy might be helpful to
      predict the parametrial status of patients with early stage cervical cancer. In
      addition, the results of this meta-analysis are helpful for designing further
      prospective clinical trials.

PMID- 29177591
TI  - MicroRNA-21 promotes proliferation, migration, and invasion of cervical cancer
      through targeting TIMP3.
AB  - BACKGROUND: The expression of microRNA-21 (miR-21) is up-regulated in various
      cancers, including cervical cancer. However, the function of miR-21 through
      tissue inhibitor of metalloproteinase 3 (TIMP3) on the proliferation, migration,
      and invasion in cervical cancer is still unclear. METHODS: A total of 60 paired
      fresh cervical cancer tissues, the corresponding adjacent non-neoplastic tissues
      and serum samples were collected from cervical cancer patients, while 60 matched
      normal tissues and serum samples were collected from the control group. MiR-21
      expression was evaluated by quantitative real-time polymerase chain reaction (qRT
      PCR). TIMP3 expression was evaluated by Western blot and qRT-PCR. Cell
      proliferation was determined by MTT assay. Migratory and invasive activities were
      assessed by cell migration and invasion assays, respectively. Luciferase reporter
      assay was employed to validate the direct targeting of TIMP3 by miR-21. RESULTS:
      MiR-21 was up-regulated in cervical cancer tissues and serum samples, in
      contrast, TIMP3 was down-regulated in cervical cancer tissues. MiR-21 promoted
      the proliferation, viability and the migratory and invasive activities of
      cervical cancer cells through targeting TIMP3. Overexpression of TIMP3 attenuated
      the positive effects of miR-21. CONCLUSIONS: These findings provide a novel
      insight into the molecular functions of miR-21 in cervical cancer, which may be
      used as a diagnostic and prognostic biomarker for the treatment of cervical
      cancer in the future.

PMID- 29177592
TI  - Hyperandrogenemia and ovarian reserve in patients with Mayer-Rokitansky-Kuster
      Hauser syndrome type 1 and 2: potential influences on ovarian stimulation.
AB  - PURPOSE: This study aimed to analyze the hormone profiles, to detect the rate of
      hyperandrogenemia and to investigate the potential effect of Mayer-Rokitansky
      Kuster-Hauser syndrome (MRKHS) on ovarian reserve, as reflected by the serum Anti
      Mullerian hormone (AMH) levels. Clinical implications were analyzed by including
      our own experiences with three patients after ovarian stimulation in preparation
      for uterus transplantation. METHODS: Serum samples of 100 patients with MRKHS (50
      patients with MRKHS type 1 and 50 with type 2) were analyzed and compared to 50
      individually age-matched healthy controls. Blood samples for hormone analyses
      were collected routinely during the clinical visit. RESULTS: The mean age was
      20.0 years for MRKHS type 1, MRKHS type 2 and healthy controls. Compared to
      healthy controls, there was no significant difference in AMH values in the MRKH
      patients. As shown in previous studies, the proportion of hyperandrogenemia
      without clinical symptoms was significantly higher in MRKHS type 1 (52%; p <
      0.001) and type 2 (56%; p < 0.001) patients when compared to age-matched
      controls. In preparation for uterus transplantation, three patients were
      stimulated with FSH/hMG for mean 14.2 days and the mean number of aspirated
      oocytes was 13.2 (3-22), while 8.3 (2-10) oocytes could be fertilized and
      cryopreserved. The mean fertilization rate was 51.2% (30-67%). CONCLUSION: The
      rate of hyperandrogenemia was significantly higher in MRKH patients compared to
      healthy age-matched controls. Though, ovarian reserve (AMH level) was not reduced
      compared to controls. Future studies are needed to identify optimal ovarian
      stimulation protocols as well as to implement a systematic multicenter reporting
      system.

PMID- 29177593
TI  - Practical recommendations for fertility preservation in women by the FertiPROTEKT
      network. Part I: Indications for fertility preservation.
AB  - PURPOSE: Most guidelines about fertility preservation are predominantly focused
      on scientific evidence, but are less practically orientated. Therefore,
      practically oriented recommendations are needed to support the clinician in daily
      practice. METHODS: A selective literature search was performed based on the
      clinical and scientific experience of the authors, focussing on the most relevant
      diseases and gynaecological cancers. This article (Part I) provides information
      on topics that are essential for the fertility preservation indication, such as
      disease prognosis, disease therapy and its associated risks to fertility,
      recommending disease-specific fertility preservation measures. Part II
      specifically focusses on fertility preservation techniques. RESULTS: In breast
      cancer patients, fertility preservation such as ovarian tissue and oocyte
      cryopreservation is especially recommended in low-stage cancer and in women < 35
      years of age. In Hodgkin's lymphoma, the indication is mainly based on the
      chemotherapy regime as some therapies have very low, others very high
      gonadotoxicity. In borderline ovarian tumours, preservation of fertility usually
      is achieved through fertility sparing surgery, ovarian stimulation may also be
      considered. In cervical cancer, endometrial cancer, rheumatic diseases and other
      malignancies such as Ewing sarcoma, colorectal carcinoma, non-Hodgkin lymphoma,
      leukaemia etc., several other factors must be considered to enable an individual,
      stage-dependent decision. CONCLUSION: The decision for or against fertility
      preservation depends on the prognosis, the risks to fertility and individual
      factors such as prospective family planning.

PMID- 29177595
TI  - Practice patterns and survival outcomes of intracranial germinoma: an analysis of
      the National Cancer Database.
AB  - The goal of the study is to examine the practice pattern and survival outcome of
      adult and pediatric patients with intracranial germinoma. Patients from the
      National Cancer Database (NCDB) brain tumor registry between the years 2004-2014
      with intracranial germinoma were extracted for analysis. Patients who had distant
      metastasis, received no treatments, or only surgery/chemotherapy alone were
      excluded. An age cutoff of > 21 years old was used to define the pediatric
      population. Patients were stratified by the treatments radiation therapy alone
      (RT) and chemotherapy followed by radiation therapy (C + RT). 445 patients with
      intracranial germinoma meeting our inclusion criteria were identified. Of the
      adult patients, 65.7% received RT and 34.3% received C + RT, compared to the
      pediatric patients, where 31.8% received RT and 68.2% received C + RT. Those
      patients who received C + RT had a lower radiation dose compared to the RT group
      (p < 0.001). The 5 and 10 year overall survival (OS) for the entire cohort was
      92.6 and 87.9%, respectively. Univariate analysis demonstrated improved OS with
      younger age, private insurance, C + RT treatment, and pediatric patients. Only
      age and insurance type remained significant on multivariate analysis. The 5 year
      OS was 92.6% (RT) versus 97.2% (C + RT) (p = 0.307) and 83.4% (RT) versus 95.4%
      (C + RT) (p = 0.122) in the pediatric and adult patients, respectively. There is
      a higher use of C + RT with an accompanied reduction in RT dose in the treatment
      of intracranial germinoma. There is no difference in survival between the
      treatment approaches of RT or C + RT in the NCDB patient cohort.

PMID- 29177594
TI  - Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic
      patients with glioblastoma.
AB  - Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients
      with GB from RedLANO follow-up registry were included. All patients underwent
      surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp
      platform). Information was recorded regarding demographics, seizure timing, anti
      epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months,
      and main side effects of AEDs. The relationship between epilepsy treatment and
      overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were
      male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27%
      were given another AED and 36% did not require any AED. Choice of AED was not
      associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor
      site (p = 0.34). Seizures and AED requirement were greater in those having
      primary GB (p = 0.04). After starting an AED, the mean time until next crisis was
      9.9 days (SD +/- 6.3), which was shorter in those receiving LEV (p = 0.03); mean
      number of seizures during the first 3 and 6 months were 2.9 and 4, respectively.
      Most patients treated with LEV (n = 46) required less than two medication
      adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less
      patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally,
      patients receiving LEV had significantly less adverse effects compared to
      patients treated with another AED. OS was significantly higher in the group
      treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047).
      Patients treated with LEV had better seizure control and longer OS compared to
      other AEDs.

PMID- 29177596
TI  - Sintering Behavior of Spark Plasma Sintered SiC with Si-SiC Composite
      Nanoparticles Prepared by Thermal DC Plasma Process.
AB  - The Si-coated SiC (Si-SiC) composite nanoparticle was prepared by non-transferred
      arc thermal plasma processing of solid-state synthesized SiC powder and was used
      as a sintering additive for SiC ceramic formation. Sintered SiC pellet was
      prepared by spark plasma sintering (SPS) process, and the effect of nano-sized Si
      SiC composite particles on the sintering behavior of micron-sized SiC powder was
      investigated. The mixing ratio of Si-SiC composite nanoparticle to micron-sized
      SiC was optimized to 10 wt%. Vicker's hardness and relative density was increased
      with increasing sintering temperature and holding time. The relative density and
      Vicker's hardness was further increased by reaction bonding using additional
      activated carbon to the mixture of micron-sized SiC and nano-sized Si-SiC. The
      maximum relative density (97.1%) and Vicker's hardness (31.4 GPa) were recorded
      at 1800  degrees C sintering temperature for 1 min holding time, when 0.2 wt%
      additional activated carbon was added to the mixture of SiC/Si-SiC.

PMID- 29177597
TI  - Aggressive pituitary adenomas: is pathology the only feature of aggressiveness?

PMID- 29177598
TI  - Systemic metabolism and energy consumption after microsurgical clipping and
      endovascular coiling for aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: The postoperative metabolic states of subarachnoid hemorrhage (SAH)
      patients were investigated using indirect calorimetry (IDC) and various
      nutritional evaluations to establish any difference in perioperative metabolic
      and nutritional states between microsurgical and endovascular treatment. METHODS:
      This study included 30 acute aneurysmal SAH patients with ruptured intracranial
      aneurysms treated by surgical clipping (n = 16) or coil embolization (n = 14) at
      a single institute. The resting energy expenditure (REE) and respiratory quotient
      were measured using IDC on days 1, 4, 7, 10, 14, and 17-21 after the operation.
      Various blood tests, including C-reactive protein (CRP) and prealbumin, were
      evaluated on the same days. RESULTS: The clipping group showed a significant
      increase in REE/basal energy expenditure (BEE) compared with the coiling group on
      days 1 and 4 (p = 0.04 and 0.03, respectively). No significant differences were
      found on days 7, 10, 14, and 17-21. The mean REE/BEE on days 1-14 and 1-21 showed
      no significant differences between the groups with repeated measures analysis of
      variance. The clipping group showed a significant decrease of prealbumin on day 4
      and significant increase in CRP on days 1, 4, and 7. CONCLUSIONS: The clipping
      group was in the hypermetabolic state compared with the coiling group during the
      very early postoperative period. However, the difference associated with the
      treatment modality was relatively small compared to the effects of the SAH and of
      the sequelae.

PMID- 29177600
TI  - Pagers, Smartphones, and HIPAA: Finding the Best Solution for Electronic
      Communication of Protected Health Information.
AB  - Electronic communication is a topic that applies broadly to the professional
      activities of every physician and the pager has been the gold standard of
      communication for decades. We believe that this is a dated technology that is
      holding clinicians back from better, more efficient alternatives, particularly
      smartphones. In this manuscript, we examine the paradoxical reliance on pagers in
      academic medicine, at a time when the use of smartphones and text messaging is
      the subject of intense scrutiny with respect to its standing under the Health
      Insurance Portability and Accountability Act (HIPAA). We provide previously
      unreported data regarding the electronic communication practices of academic
      medical centers in the United States, which we obtained through a survey of
      Designated Institutional Officials. These data highlight both the controversy
      around text messaging and HIPAA and a puzzling widespread reliance on pagers as
      an alternative.

PMID- 29177599
TI  - Obesity in Children: Definition, Etiology and Approach.
AB  - Childhood obesity is an important public health issue worldwide. Urbanization,
      sedentary lifestyle and change in food habits are the chief reasons behind this
      pandemic. In a small proportion of children, obesity is the result of endocrine,
      syndromic or monogenic causes. The present paper summarizes the methods,
      definitions and cut-offs for identification of obesity in children. We have
      briefly reviewed the various techniques used for estimation of body fat in
      children and the cut-offs for defining obesity based on body fat percentage, and
      the reference curves based on body mass index and waist circumference. The
      etiology of obesity in children, including individual behaviors, macro- and micro
      environmental influences, and endocrine causes have been discussed, and an
      approach to etiological assessment of obese children has been presented. Special
      emphasis has been laid on clinical pointers that suggest the presence of
      syndromic, endocrine or monogenic forms of obesity, such as, short stature,
      dysmorphism, neurocognitive impairment and early age at onset.

PMID- 29177601
TI  - Streptomyces ginkgonis sp. nov., an endophyte from Ginkgo biloba.
AB  - A novel endophytic actinomycete strain, designated KM-1-2T, was isolated from
      seeds of Ginkgo biloba at Yangling, China. A polyphasic approach was used to
      study the taxonomy of strain KM-1-2T and it was found to show a range of
      phylogenetic and chemotaxonomic properties consistent with those of members of
      the genus Streptomyces. The diamino acid of the cell wall peptidoglycan was
      identified as LL-diaminopimelic acid. No diagnostic sugars were detected in whole
      cell hydrolysates. The predominant menaquinones were identified as MK-9(H6) and
      MK-9(H8). The diagnostic phospholipids were found to be phosphatidylethanolamine
      and phosphatidylcholine. The DNA G + C content of the novel strain was determined
      to be 72.9 mol%. The predominant cellular fatty acids (> 10.0 %) were identified
      as iso-C14 : 0, iso-C16 : 0, C16 : 0 and C17 : 0 cyclo. Phylogenetic analysis
      based on the 16S rRNA gene sequence revealed that the strain is closely related
      to Streptomyces carpaticus JCM 6915T (99.3%), Streptomyces harbinensis DSM 42076T
      (98.9%) and Streptomyces cheonanensis JCM 14549T (98.5%). DNA-DNA hybridizations
      with these three close relatives gave similarity values of 39.1 +/- 1.9, 35.8 +/-
      2.3, and 47.4 +/- 2.7%, respectively, which indicated that strain KM-1-2T
      represents a novel species of the genus Streptomyces. This is consistent with the
      morphological, physiological and chemotaxonomic data. Cumulatively, these data
      suggest that strain KM-1-2T represents a novel Streptomyces species, for which
      the name Streptomyces ginkgonis sp. nov. is proposed, with the type strain KM-1
      2T (= CCTCC AA2016004T = KCTC 39801T).

PMID- 29177602
TI  - Does tacrolimus have any positive impact on outcome of post-transplant breast
      cancer patients?

PMID- 29177604
TI  - Obesity's impact on survival is independent of dose adjustments in neoadjuvant
      chemotherapy in women with breast cancer.

PMID- 29177603
TI  - Impact of multi-gene mutational profiling on clinical trial outcomes in
      metastatic breast cancer.
AB  - PURPOSE: Next-generation sequencing (NGS) has identified recurrent genomic
      alterations in metastatic breast cancer (MBC); however, the clinical utility of
      incorporating routine sequencing to guide treatment decisions in this setting is
      unclear. We examine the frequency of genomic alterations in MBC patients from
      academic and community hospitals and correlate with clinical outcomes. METHODS:
      MBC patients with good performance status were prospectively recruited at the
      Princess Margaret Cancer Centre (PM) in Canada. Molecular profiling on DNA
      extracted from FFPE archival tissues was performed on the Sequenom MassArray
      platform or the TruSeq Amplicon Cancer Panel (TSACP) on the MiSeq platform.
      Clinical trial outcomes by RECIST 1.1 and time on treatment were reviewed
      retrospectively. RESULTS: From January 2012 to November 2015, 483 MBC patients
      were enrolled and 440 were genotyped. At least one somatic mutation was
      identified in 46% of patients, most commonly in PIK3CA (28%) or TP53 (13%). Of
      203 patients with >= 1 mutation(s), 15% were treated on genotype-matched and 9%
      on non-matched trials. There was no significant difference for median time on
      treatment for patients treated on matched vs. non-matched therapies (3.6 vs. 3.8
      months; p = 0.89). CONCLUSIONS: This study provides real-world outcomes on
      hotspot genotyping and small targeted panel sequencing of MBC patients from
      academic and community settings. Few patients were matched to clinical trials
      with targeted therapies. More comprehensive profiling and improved access to
      clinical trials may increase therapeutic options for patients with actionable
      mutations. Further studies are needed to evaluate if this approach leads to
      improved clinical outcomes.

PMID- 29177605
TI  - Evaluation of applying IHC4 as a prognostic model in the translational study of
      Intergroup Exemestane Study (IES): PathIES.
AB  - BACKGROUND: Intergroup Exemestane Study (IES) was a randomised study that showed
      a survival benefit of switching adjuvant endocrine therapy after 2-3 years from
      tamoxifen to exemestane. This PathIES aimed to assess the role of
      immunohistochemical (IHC)4 score in determining the relative sensitivity to
      either tamoxifen or sequential treatment with tamoxifen and exemestane. PATIENTS
      AND METHODS: Primary tumour samples were available for 1274 patients (27% of IES
      population). Only patients for whom the IHC4 score could be calculated (based on
      oestrogen receptor, progesterone receptor, HER2 and Ki67) were included in this
      analysis (N = 430 patients). The clinical score (C) was based on age, grade,
      tumour size and nodal status. The association of clinicopathological parameters,
      IHC4(+C) scores and treatment effect with time to distant recurrence-free
      survival (TTDR) was assessed in univariable and multivariable Cox regression
      analyses. A modified clinical score (PathIEscore) (N = 350) was also estimated.
      RESULTS: Our results confirm the prognostic importance of the original IHC4,
      alone and in conjunction with clinical scores, but no significant difference with
      treatment effects was observed. The combined IHC4 + Clinical PathIES score was
      prognostic for TTDR (P < 0.001) with a hazard ratio (HR) of 5.54 (95% CI 1.29
      23.70) for a change from 1st quartile (Q1) to Q1-Q3 and HR of 15.54 (95% CI 3.70
      65.24) for a change from Q1 to Q4. CONCLUSION: In the PathIES population, the
      IHC4 score is useful in predicting long-term relapse in patients who remain
      disease-free after 2-3 years. This is a first trial to suggest the extending use
      of IHC4+C score for prognostic indication for patients who have switched
      endocrine therapies at 2-3 years and who remain disease-free after 2-3 years.

PMID- 29177607
TI  - Building Healthy Start Grantees' Capacity to Achieve Collective Impact: Lessons
      from the Field.
AB  - Purpose While Healthy Start has emphasized the need for multi-sectorial community
      engagement and collaboration since its inception, in 2014 Healthy Start adopted
      Collective Impact (CI) as a framework for reducing infant mortality. This paper
      describes the development of a peer-focused capacity-building strategy that
      introduced key elements of CI and preliminary findings of Healthy Start grantees'
      progress with using CI as an approach to collaboration. Description The
      Collective Impact Peer Learning Networks (CI-PLNs) consisted of eight 90-min
      virtual monthly meetings and one face-to-face session that reviewed CI pre
      conditions and conditions. Evaluation sources included: a facilitated group
      discussion at the final CI-PLN exploring grantee CI and CAN accomplishments (n =
      57); routine evaluations (n = 144 pre, 46 interim, and 40 post PLN) examining
      changes in knowledge and practices regarding CI; and post CI-PLN implementation,
      three in-depth interviews with grantees who volunteered to discuss their
      experience with CI and participation in the CI-PLN. Assessment CI-PLN
      participants reported increased knowledge and confidence in the application of
      CI. Several participants reported that the CI-PLN created a space for engaging in
      peer sharing challenges, successes, and best practices. Participants also
      reported a desire to continue implementing CI and furthering their learning.
      Conclusion The CI-PLNs met the initial goal of increasing Healthy Start grantees'
      understanding of CI and determining the initial focus of their efforts. By year
      five, the EPIC Center anticipates Healthy Start CANs will have a sustainable
      infrastructure in place that supports the established common agenda, shared
      measures, and ongoing and meaningful inclusion of community members.

PMID- 29177606
TI  - The Association Between Child and Family Characteristics and the Mental Health
      and Wellbeing of Caregivers of Children with Autism in Mid-Childhood.
AB  - We examined predictors of mental health difficulties and wellbeing in caregivers
      of children with autism in the Pre-school Autism Communication Trial cohort in
      middle childhood (N = 104). Child's intellectual disability, daily living skills
      impairment, elevated emotional and behavioural difficulties, high educational
      level of caregiver and household income below the median significantly predicted
      caregivers' mental health difficulties, but autism severity, child communication
      skills and family circumstances did not. Lower caregiver mental wellbeing was
      predicted by elevated child emotional and behavioural difficulties. The need to
      support the mental health and wellbeing of caregivers of children with autism is
      discussed in light of the results.

PMID- 29177608
TI  - Identification of Educational Gaps Among Oncologists Who Manage Patients with
      Pancreatic Cancer.
AB  - INTRODUCTION: Pancreatic ductal adenocarcinoma (PDA) is associated with poor
      outcomes and presents oncologists with a myriad of clinical challenges. This
      study was conducted to assess oncologists' practice patterns and to identify the
      greatest areas of need for future PDA continuing medical education (CME)
      programs. METHODS: Case vignettes have been validated as an effective tool to
      assess how physicians approach and treat a wide array of diseases. In order to
      assess practice patterns for resectable, locally advanced unresectable, and
      metastatic PDA, an online case vignette survey was distributed to practicing
      medical oncologists. RESULTS: Responses from 150 US-practicing oncologists were
      analyzed, and several key opportunities for future CME programs were identified.
      For case 1 (patient with resectable PDA), 44% of oncologists did not select an
      evidence-based adjuvant chemotherapy regimen. For case 2 (patient with locally
      advanced PDA who develops metastases and neuropathy after first-line nab
      paclitaxel/gemcitabine followed by chemoradiation), 57% of oncologists did not
      select an evidence-based second-line chemotherapy regimen, and 35% selected a
      regimen containing oxaliplatin, a chemotherapeutic known to cause neuropathy. For
      case 3 (patient with a pancreatic mass and liver metastases), only 34% of
      oncologists recommended a biopsy, chest imaging, and liver function tests which
      should be standard of care assessments with this presentation. For all three
      cases, clinical trial referral was selected by fewer than 5% of respondents.
      CONCLUSIONS: This study identified appreciable discrepancies between oncologists'
      recommendations and standard evidence-based guidelines. Well-designed CME
      programs may help to bridge the educational gaps identified and improve adherence
      to practice guidelines.

PMID- 29177609
TI  - Disregulation of miR-216a and miR-217 in Gastric Cancer and Their Clinical
      Significance.
AB  - OBJECTIVE: The majority of gastric cancer (GC) diagnoses occur at the middle or
      late stage of the disease, indicating that finding novel biomarkers that could be
      detectable at earlier stage is urgently needed. Accumulating studies have shown
      that microRNAs, a class of tiny single-stranded RNAs, play important roles in
      multiple biological processes including cancer development. The present study
      aimed to evaluate the effect of miR-216a and miR-217 in GC. MATERIAL AND METHODS:
      The real-time quantitative reverse-transcription PCR was exploited to identify
      and compare the expression levels of miR-216a and miR-217 in 37 pairs of samples
      of gastric cancer tissue and adjacent normal tissue. Superimposed on this, the
      potential relationship between miR-216a/217 levels and clinicopathological
      parameters in patients suffering GC was explored. RESULTS: The results obtained
      from this study showed that the miR-216a is significantly upregulated in gastric
      cancer tissues, compared with adjacent normal tissues, but the altered expression
      of miR-217 was not significant. For miR-216a/217, no significant correlations
      were detected between expression levels of these miRNAs and clinical and
      pathological characteristics of patients. CONCLUSION: This prospective study
      proposes that upregulation of miR-216a might represent an important mechanism for
      the development of gastric cancer.

PMID- 29177610
TI  - Findings from an outbreak of carbapenem-resistant Klebsiella pneumoniae emphasize
      the role of antibiotic treatment for cross transmission.
AB  - PURPOSE: In January 2015, we noticed by rectal swab analyses that seven of 23
      patients at an early rehabilitation ward had been colonized with carbapenem
      resistant Klebsiella pneumoniae (CKP). Here, we describe risk factors for CKP
      acquisition. METHODS: In the present study, the outbreak is described and risk
      factors for CKP acquisition are examined, e.g., antibiotic treatment.
      Microbiological analyses including corresponding results were examined to study
      when colonization with CKP occurred and whether patients had suffered from
      diarrhea. To examine whether spread of bacteria was clonal, multi-locus sequence
      typing as well as Xbal macrorestriction and pulsed-field gel electrophoresis was
      performed. The presence of carbapenmase was examined by PCR analysis. Through
      univariate analysis of risk factors in the small study sample, the role of
      antibiotic consumption, isolation procedures, patient's age, gender, and Barthel
      index on colonization was elucidated. RESULTS: Clonal spread of the novel
      sequence type (ST)2255 was identified. Additionally, one patient was colonized
      with Escherichia coli and Serratia marcescens, both resistant to carbapenems,
      while a further patient carried another carbapenem-resistant E. coli strain. In
      all isolates, carbapenemase gene bla OXA-48 was found to be located on a
      conjugative plasmid (60 kb), suggesting in vivo transmission from CKP to E. coli
      and S. marcescens. Univariate tests indicated that antibiotic treatment was the
      only risk factor showing a significant association with being colonized by CKP.
      In addition, the likelihood of diarrhea appeared to be higher in this group.
      Antibiotic treatment was associated with CKP colonization, whereas patients' age,
      gender, Barthel index at admission, and residence with a CKP-colonized roommate
      were not. Diarrhea also seemed to support to distribution of CKP. CONCLUSIONS: In
      this small outbreak, antibiotic treatment seemed to be the predominant risk
      factor for monoclonal transmission of bla OXA-48 positive CKP.

PMID- 29177611
TI  - Appropriate non-carbapenems are not inferior to carbapenems as initial empirical
      therapy for bacteremia caused by extended-spectrum beta-lactamase-producing
      Enterobacteriaceae: a propensity score weighted multicenter cohort study.
AB  - The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta
      lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive.
      We conducted a multicenter retrospective cohort study to evaluate the efficacy of
      empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical
      records of individuals who were diagnosed with ESBL-B were reviewed between
      January 2010 and December 2014 at four university hospitals in Korea. Patients
      were classified into non-carbapenem and carbapenem groups according to the
      empirical antibiotic regimen. Patients treated with appropriate empirical
      antibiotics and who subsequently received carbapenems as definitive therapy were
      included in the analysis. The inverse probability of treatment weights, a
      statistical method that adjusts baseline statistics by giving weights based on
      propensity score, was used. During the study period, 232 adequately treated
      patients with ESBL-B were included in the analysis: 49 patients in the non
      carbapenem group and 183 in the carbapenem group. The baseline characteristics
      and severity of infection were similar after propensity score weighting. The 30
      day mortality rates for the two groups were not statistically significantly
      different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a
      multivariate analysis, empirical treatment with non-carbapenem antibiotics was
      not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P =
      0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam
      was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37
      4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as
      initial empirical therapy for ESBL-B.

PMID- 29177612
TI  - Evaluation of colistin stability in agar and comparison of four methods for MIC
      testing of colistin.
AB  - Susceptibility testing for colistin remains challenging primarily due to its
      inherent properties. We evaluated colistin stability in agar and reproducibility
      of colistin MICs obtained by agar dilution, broth macro- and micro-dilution and
      MIC gradient strips on 3-7 iterations of each method using clinical Klebsiella
      pneumoniae (susceptible-CS, and resistant-CR, n = 2 each), mcr-harboring
      Escherichia coli (n = 2), and reference strains E. coli ATCC25922 and Pseudomonas
      aeruginosa ATCC27853. MICs for reference strains were not in the given range
      using Etest and broth microdilution (ATCC25922, 0.125 and 4 MUg/ml,
      respectively). MICs of CR-1 and CR-2, and of the mcr-harboring E. coli showed
      high concordance between agar and broth dilution varying up to one 2-fold
      dilution. However, remarkable variations were observed on broth dilution with CS
      1 and CS-2 (MIC range 0.25-32 and 0.5-64 MUg/ml, respectively); whereas for agar
      dilution the MIC for both CS strains was 0.5 MUg/ml in all the runs. MICs
      obtained by MIC gradient strips were lower than those obtained by dilution
      methods (1-2 dilutions for CS and mcr strains, and up to five dilutions for CR
      strains). To confirm uniform distribution of colistin in agar, a single strain
      was spotted in five different regions of the same plate. All spots showed
      concordant growth with maximum one dilution difference. No effect on MIC was
      found due to storage of colistin-containing agar plates for 7 days at 4  degrees
      C. In our hands, agar dilution was superior in terms of reproducibility and
      robustness, compared to broth dilution methods, for colistin MIC determination.

PMID- 29177614
TI  - The quality of information on the internet relating to top-selling dietary
      supplements in the Czech Republic.
AB  - Background The purchase of dietary supplements (DS) via the Internet is
      increasing worldwide as well as in the Czech Republic. Objective The aim of the
      study is to evaluate the quality of information on DS available on the Internet.
      Setting Czech websites related to dietary supplements. Methods A cross-sectional
      study was carried out involving the analysis of information placed on the
      websites related to the 100 top-selling DS in the Czech Republic in 2014,
      according to IMS Health data. Main outcome measure The following criteria were
      evaluated: contact for the manufacturer, recommended dosage, information on
      active substances as well as overall composition, permitted health claims, % of
      the daily reference intake value (DRIV) for vitamins and minerals, link for
      online counseling, pregnancy/breastfeeding, allergy information,
      contraindications, adverse reactions, and supplement-drug interactions (some
      criteria were evaluated from both points of view). Results A total of 199 web
      domains and 850 websites were evaluated. From the regulatory point of view, all
      the criteria were fulfilled by 11.3% of websites. Almost 9% of the websites
      reported information referring to the treatment, cure, or prevention of a
      disease. From the clinical point of view, all the criteria were only met by one
      website. Conclusions The quality of information related to DS available on the
      Internet in the Czech Republic is quite low. The consumers should consult a
      specialist when using DS purchased online.

PMID- 29177613
TI  - Retinal Pigment Epithelium and Photoreceptor Preconditioning Protection Requires
      Docosanoid Signaling.
AB  - Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are necessary for
      functional cell integrity. Preconditioning (PC), as we define it, is an acquired
      protection or resilience by a cell, tissue, or organ to a lethal stimulus enabled
      by a previous sublethal stressor or stimulus. In this study, we provide evidence
      that the omega-3 fatty acid docosahexaenoic acid (DHA) and its derivatives, the
      docosanoids 17-hydroxy docosahexaenoic acid (17-HDHA) and neuroprotectin D1
      (NPD1), facilitate cell survival in both in vitro and in vivo models of retinal
      PC. We also demonstrate that PC requires the enzyme 15-lipoxygenase-1 (15-LOX-1),
      which synthesizes 17-HDHA and NPD1, and that this is specific to docosanoid
      signaling despite the concomitant release of the omega-6 arachidonic acid and
      eicosanoid synthesis. These findings advocate that DHA and docosanoids are
      protective enablers of PC in photoreceptor and retinal pigment epithelial cells.

PMID- 29177615
TI  - ETV6-ABL1 fusion combined with monosomy 7 in childhood B-precursor acute
      lymphoblastic leukemia.
AB  - ETV6-ABL1 fusion is a rare but recurrent oncogenic lesion found in childhood B
      cell precursor acute lymphoblastic leukemia (BCP-ALL), without an established
      chromosomal abnormality, and is associated with poor outcome. In ETV6-ABL1
      positive cases, an in-frame fusion produced by a complex rearrangement results in
      constitutive chimeric tyrosine kinase activity. Monosomy 7 is also a rare and
      unfavorable chromosomal abnormality in childhood BCP-ALL. Here, we report a 14
      year-old female BCP-ALL patient with ETV6-ABL1 fusion combined with monosomy 7.
      She was admitted to our hospital because of persistent fever. Bone marrow nuclear
      cell count on admission was 855,000/uL with 90.0% blastic cells of lymphoid
      morphology. Blasts were positive for CD10, CD19, CD20, CD34, cyCD79a, cyTdT, HLA
      DR, and CD66c, had a karyotype of 45, XX, - 7 [18/20] and a split signal for ABL1
      FISH probe (92.7%), and were sensitive to tyrosine kinase inhibitors, imatinib
      and dasatinib, in vitro. ETV6-ABL1 fusion transcript was identified by whole
      transcriptome sequencing and confirmed by RT-PCR. She was treated with the high
      risk protocol based on ALL-BFM 95, achieved complete remission (CR) after
      induction chemotherapy, and maintained CR for 4 months. To our knowledge, this is
      the first report of ETV6-ABL1 fusion combined with monosomy 7 in childhood BCP
      ALL.

PMID- 29177617
TI  - Do Parents Model Gestures Differently When Children's Gestures Differ?
AB  - Children with autism spectrum disorder (ASD) or with Down syndrome (DS) show
      diagnosis-specific differences from typically developing (TD) children in gesture
      production. We asked whether these differences reflect the differences in
      parental gesture input. Our systematic observations of 23 children with ASD and
      23 with DS (Mages = 2;6)-compared to 23 TD children (Mage = 1;6) similar in
      expressive vocabulary-showed that across groups children and parents produced
      similar types of gestures and gesture-speech combinations. However, only children
      but not their parents-showed diagnosis-specific variability in how often they
      produced each type of gesture and gesture-speech combination. These findings
      suggest that, even though parents model gestures similarly, the amount with which
      children produce each type largely reflects diagnosis-specific abilities.

PMID- 29177618
TI  - Parent-Implemented Bedtime Fading and Positive Routines for Children with Autism
      Spectrum Disorders.
AB  - Sleep disorders affect a large portion of those with autism spectrum disorder.
      Behavioural interventions have been found to increase appropriate sleep
      behaviours. This study sought to examine the efficacy of two stimulus control
      interventions (bedtime fading and positive routines) on total sleep duration,
      sleep onset latency and frequency and duration of night wakings for children with
      autism using two multiple baseline designs. Secondary dependent variables,
      namely, educational opportunities, challenging behaviours, parent acceptance and
      social validity were also analysed. Results suggest some efficacy for both
      interventions. Increased total sleep duration and decreased sleep onset latency
      were achieved with bedtime fading. Positive routines showed mixed results with
      decreased sleep onset latency and increased total sleep duration for two of three
      participants.

PMID- 29177616
TI  - Medial Frontal Lobe Neurochemistry in Autism Spectrum Disorder is Marked by
      Reduced N-Acetylaspartate and Unchanged Gamma-Aminobutyric Acid and Glutamate +
      Glutamine Levels.
AB  - The nature of neurochemical changes in autism spectrum disorder (ASD) remains
      controversial. We compared medial prefrontal cortex (mPFC) neurochemistry of
      twenty high-functioning children and adolescents with ASD without associated
      comorbidities and fourteen controls. We observed reduced total N-acetylaspartate
      (tNAA) and total creatine, increased Glx/tNAA but unchanged glutamate + glutamine
      (Glx) and unchanged absolute or relative gamma-aminobutyric acid (GABA+) in the
      ASD group. Importantly, both smaller absolute and relative GABA+ levels were
      associated with worse communication skills and developmental delay scores
      assessed by the autism diagnostic interview-revised (ADI-R). We conclude that
      tNAA is reduced in the mPFC in ASD and that glutamatergic metabolism may be
      altered due to unbalanced Glx/tNAA. Moreover, GABA+ is related to autistic
      symptoms assessed by the ADI-R.

PMID- 29177619
TI  - Two-step approach to avoid obstruction of the coronary ostium during
      transcatheter aortic valve implantation with the SAPIEN 3.

PMID- 29177621
TI  - Editors' Note (Update): Medical Student Moonlighting in the Psychiatry Emergency
      Room.

PMID- 29177622
TI  - Call for Neuroradiology Editor-in-Chief candidates.

PMID- 29177620
TI  - Revisiting traumatic cardiac arrest: should CPR be initiated?
AB  - OBJECTIVES: Traumatic cardiac arrest (TCA) represents a unique problem, and poses
      difficult challenges in the care of trauma patients. Although the literature has
      suggested that attempted resuscitation from TCA in trauma is futile and
      consumptive of medical and human resources, studies have recently demonstrated
      that the outcome of TCA is comparable cardiac arrest secondary to non-traumatic
      events. The objective of this study was to determine the incidence, predictors,
      and outcomes following TCA. METHODS: We retrospectively reviewed 124 adult
      patients with TCA over a period of 5 years (July 2010 to June 2014).
      Cardiopulmonary resuscitation (CPR) occurred either in the field, en route, or in
      the emergency department at our Level I Trauma Center. Patients' demographics,
      clinical data, CPR-related variables, and outcomes were extracted from both the
      electronic and paper medical records. RESULTS: The median age of the group was 37
      (IQR 38), and the median ISS was 37 (IQR 50). The most common cardiac rhythm
      observed was pulseless electrical activity (PEA, 55%). While 31.4% of patients
      achieved a return of spontaneous circulation (ROSC), only 7.3% survived with a
      complete neurological recovery (CNR). In blunt injury patients, the mortality
      rate after CPR was higher in motor-vehicle-related injuries than falls from
      heights (93.1 vs 72.3%, OR 5.06, 95% CI 0.95-27.0, p < 0.05). In penetrating
      injuries, the mortality rate after CPR was higher in patients with trauma to the
      torsos than those suffering injuries to the head, neck, face, and extremities
      combined (100 vs 81.3%, OR 0.049, 95% CI 0.0024-1.008, p < 0.001). Two variables
      predicted failure of CPR were prolonged time interval hospital transport (OR
      0.42, 95% CI 0.22-0.80, p < 0.01) and high injury severity score (OR 0.97, 95% CI
      0.94-1.00, p < 0.05). However, CPR duration/location (out-of-hospital or in
      hospital), head injury, and day/night shifts in ED were not associated with the
      above outcome. When comparing age groups, the mortality was significantly higher
      in patients < 65 years than those >= 65 years (OR 0.2619, 95% CI 0.09485-0.9703,
      p = 0.0182). CONCLUSION: Although survival after CPR among trauma patients
      continues to have dismal outcomes, advanced cardiac life support should be
      initiated regardless of the initial EKG rhythm. Ultimately, both a rapid response
      time and transport to the ED are of the utmost importance to survival.

PMID- 29177623
TI  - Expression of single-domain antibody in different systems.
AB  - Camelid single-domain antibodies (sdAbs, VHHs, or Nanobodies(r)) are types of
      antibody fragments that are composed of the heavy-chain variable domain only.
      These VHHs possess unique structural and functional features, as they are small
      in size and exhibit thermal stability and high solubility. Compared to
      conventional antibodies, VHHs can be manufactured in microorganisms to
      significantly save on cost, labor, and time since VHHs lack the Fc domain with
      its N-linked oligosaccharide. Until now, VHHs have been expressed in several
      kinds of production systems, ranging from prokaryotic cells, yeasts, fungi,
      insect cells, and mammalian cell lines, to plants. In this review, we focus on
      the recent production of VHHs, introduce different platforms, and summarize the
      current state of this area and its future trends. Finally, the first potential
      VHH product, produced in Pichia pastoris, will probably be available on the
      market in 2018; thus, it is of great importance to give this antibody fragment
      timely attention. This is the first review concerning the production of VHHs in
      laboratory settings.

PMID- 29177624
TI  - Production of Monascus pigments as extracellular crystals by cell suspension
      culture.
AB  - It is generally accepted that Monascus pigments are predominantly cell-bound,
      including both intracellular and surface-bound pigments. This long-term
      misconception was corrected in the present work. Production of extracellular
      crystal pigments by submerged culture of Monascus sp. was confirmed by
      microscopic observation and collection of Monascus pigments from extracellular
      broth by direct membrane filtration. Following up the new fact, the bioactivity
      of mycelia as whole-cell biocatalyst for biosynthesis and biodegradation of
      Monascus pigments had been detailedly examined in both an aqueous solution and a
      nonionic surfactant micelle aqueous solution. Based on those experimental
      results, cell suspension culture in an aqueous medium was developed as a novel
      strategy for accumulation of high concentration of Monascus pigments. Thus,
      glucose feeding during submerged culture in the aqueous medium was carried out
      successfully and high orange Monascus pigments concentration of near 4 g/L was
      achieved.

PMID- 29177625
TI  - Hydrometrocolpos etiology and management: past beckons the present.
AB  - Hydrometrocolpos is a rare condition in which the uterus and the vagina are
      grossly distended with a retained fluid other than pus or blood. It may present
      during the neonatal period or later at puberty. Most cases reported earlier were
      stillbirths and were diagnosed only on autopsy. Antenatal diagnosis is now
      possible with the advent of ultrasound. An early diagnosis and speedy management
      is the key to survival. Many previous case reports have focused on the varied
      clinical presentations, multiple causes, associated syndromes and/or the
      radiological diagnosis of this condition. However, management options for
      different types of hydrometrocolpos have not yet been concisely discussed. We
      have reviewed the literature and tried to summarize the management options
      applicable to most case scenarios of hydrometrocolpos.

PMID- 29177627
TI  - Virtual 3D planning of tracheostomy placement and clinical applicability of 3D
      cannula design: a three-step study.
AB  - AIM: We aimed to investigate the potential of 3D virtual planning of tracheostomy
      tube placement and 3D cannula design to prevent tracheostomy complications due to
      inadequate cannula position. MATERIALS AND METHODS: 3D models of commercially
      available cannula were positioned in 3D models of the airway. In study (1), a
      cohort that underwent tracheostomy between 2013 and 2015 was selected (n = 26).
      The cannula was virtually placed in the airway in the pre-operative CT scan and
      its position was compared to the cannula position on post-operative CT scans. In
      study (2), a cohort with neuromuscular disease (n = 14) was analyzed. Virtual
      cannula placing was performed in CT scans and tested if problems could be
      anticipated. Finally (3), for a patient with Duchenne muscular dystrophy and
      complications of conventional tracheostomy cannula, a patient-specific cannula
      was 3D designed, fabricated, and placed. RESULTS: (1) The 3D planned and post
      operative tracheostomy position differed significantly. (2) Three groups of
      patients were identified: (A) normal anatomy; (B) abnormal anatomy, commercially
      available cannula fits; and (C) abnormal anatomy, custom-made cannula, may be
      necessary. (3) The position of the custom-designed cannula was optimal and the
      trachea healed. CONCLUSIONS: Virtual planning of the tracheostomy did not
      correlate with actual cannula position. Identifying patients with abnormal airway
      anatomy in whom commercially available cannula cannot be optimally positioned is
      advantageous. Patient-specific cannula design based on 3D virtualization of the
      airway was beneficial in a patient with abnormal airway anatomy.

PMID- 29177626
TI  - Non-surgical treatment of obstructive sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS), a pervasive disease, is closely
      associated with complications such as cardiovascular diseases, neurocognitive
      diseases, and metabolic syndromes. Continuous positive airway pressure (CPAP) is
      the standard treatment for OSAS, with low compliance due to multifarious factors.
      The two other modes of ventilation, bi-level positive airway pressure (BPAP) and
      autotitrating positive airway pressure (APAP), which were developed from CPAP,
      are slightly different from CPAP in specific groups, as well as the corresponding
      treatment effect and compliance. The compliance of traditional positional therapy
      is not high, but with the emergence of the neck-based position treatment device,
      its compliance and indications have changed. Although CPAP is superior to
      mandibular advancement device (MAD) in improving AHI, MAD seems to be comparable
      to CPAP in improving other indicators. Corticosteroids and leukotriene receptor
      antagonists are effective treatments for mild OSAS children. Whether
      corticosteroids can be used in other OSAS groups and their adjunctive functions
      to CPAP remains unclear. The combination of these two kinds of drugs appears to
      be more effective than single drug. Researches on transcutaneous electrical
      stimulation are still not enough. Its effectiveness and stimulation settings
      still need further study. This review summarized the various OSAS non-surgical
      treatments from indications, treatment outcomes, compliance, adverse reactions,
      and recent progress.

PMID- 29177628
TI  - Mycophenolate mofetil following glucocorticoid treatment in Henoch-Schonlein
      purpura nephritis: the role of early initiation and therapeutic drug monitoring.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) is the most common vasculitis in
      childhood and traditionally considered as a self-limiting disease. However, renal
      involvement can unfavorably determine long-term prognosis. The reported regimens
      to treat HSP nephritis (HSPN) are diverse, indicating that the most effective
      treatment remains controversial. METHODS: This retrospective, single-center study
      involved 18 patients presenting with HSPN and nephrotic-range proteinuria. We
      aimed to investigate the efficacy and safety of mycophenolate mofetil (MMF) and
      identify a cut-off level for estimated mycophenolic acid area under the curve
      (eMPA-AUC0-12h) values, which can predict complete remission with high
      sensitivity. RESULTS: Despite prior insufficient therapeutic response to
      corticosteroids, 89% of patients showed a significant decrease in proteinuria
      after 1 month of MMF treatment. None of them relapsed during treatment; however,
      two children relapsed after discontinuation. Based on results of a receiver
      operating characteristic (ROC) analysis, an eMPA-AUC0-12h >56.4 mg*h/l was a
      predictor for complete remission within 3 months (80% sensitivity, 83.3%
      specificity, p = 0.035). During MMF administration, we encountered no adverse
      event requiring discontinuation of treatment. CONCLUSION: Our study demonstrates
      that MMF is a safe and potentially effective secondary treatment option for
      children with HSPN to achieve and maintain long-term remission without serious
      side effects. To achieve complete remission within 3 months, resolve severe
      inflammatory glomerular lesions, and avoid progression to chronic kidney disease,
      we propose timely diagnosis and early initiation of MMF with an eMPA-AUC0-12h
      value of 56.4 mg*h/l.

PMID- 29177629
TI  - A DFT study on graphene, SiC, BN, and AlN nanosheets as anodes in Na-ion
      batteries.
AB  - A great concern exists about the lifetime, cost, low-temperature performance, and
      safety of Li-ion batteries. Na-ion batteries (NIB) are an alternative to the Li
      ion batteries due to the wide availability of sodium, its low cost, and
      nontoxicity. Here, we examined the Na and Na+ adsorption on nanosheets of carbon
      (graphene), AlN, BN, and SiC to explore their potential use as an anode in NIBs.
      The interaction of atomic Na was found to play the main role in producing
      different nanosheet cell voltages. Unlike the graphene and SiC nanosheets, the
      lone pairs on the surface of the AlN and BN nanosheets hinder the Na adsorption
      and significantly increase the cell voltage. The order of magnitude of the
      nanosheet cell voltage as an anode in NIBs is as follows: AlN (1.49 V) > BN (1.46
      V) > > C (0.69 V) > SiC (0.61 V). The AlN and BN nanosheets may be appropriate
      compounds for NIBs and their cell voltages are comparable with carbon nanotubes.

PMID- 29177630
TI  - Intraoperative monitoring of sensory part of the trigeminal nerve using blink
      reflex during microvascular decompression for trigeminal neuralgia.
AB  - Intraoperative monitoring during cerebellopontine angle surgery is widely
      accepted. While techniques which monitor cranial motor nerves are commonly used,
      monitoring the sensory afferents has been challenging. Considering the reflex
      arc, blink reflex (BR) might be useful in monitoring the sensory part of the
      trigeminal nerve, the brainstem connections and the facial nerve. We describe the
      case of a patient who developed hemifacial hypoesthesia after microvascular
      decompression surgery for trigeminal neuralgia. Intraoperative BR showed a severe
      loss of R1 amplitude. BR might be a useful intraoperative technique to monitor
      the sensory part of the trigeminal nerve.

PMID- 29177631
TI  - Manipulating an internal pulse generator until twiddler's syndrome in a patient
      treated with deep brain stimulation for obsessive-compulsive disorder.
AB  - BACKGROUND: Twiddler's syndrome consists of rotation or manipulation of an
      implantable pulse generator (IPG) in its subcutaneous pocket by a patient, thus
      causing hardware malfunction. METHODS: This syndrome is being reported more
      frequently in patients treated with deep brain stimulation (DBS). RESULTS: We
      report the case of a woman who had received bed nucleus of stria terminalis
      (BNST) electrodes for obsessive-compulsive disorder (OCD) and developed
      twiddler's syndrome a few months after surgery, causing hardware malfunction due
      to obsessive manipulation of the IPG. CONCLUSION: The patient did not have
      compulsions related to touching objects at admission, thus making it difficult to
      foresee and prevent TS.

PMID- 29177632
TI  - The use of lumbar epidural injection of platelet lysate for treatment of
      radicular pain.
AB  - BACKGROUND: Epidural steroid injections (ESI) are the most common pain management
      procedure performed in the US, however evidence of efficacy is limited. In
      addition, there is early evidence that the high dose of corticosteroids used can
      have systemic side effects. We describe the results of a case series evaluating
      the use of platelet lysate (PL) epidural injections for the treatment of lumbar
      radicular pain as an alternative to corticosteroids. METHODS: Registry data was
      obtained for patients (N = 470) treated with PL epidural injections presenting
      with symptoms of lumbar radicular pain and MRI findings that were consistent with
      symptoms. Collected outcomes included numeric pain score (NPS), functional rating
      index (FRI), and a modified single assessment numeric evaluation (SANE) rating.
      RESULTS: Patients treated with PL epidurals reported significantly lower (p <
      .0001) NPS and FRI change scores at all time points compared to baseline. Post
      treatment FRI change score means exceeded the minimal clinically important
      difference beyond 1 month. Average modified SANE ratings showed 49.7% improvement
      at 24 months post-treatment. Twenty-nine (6.3%) patients reported mild adverse
      events related to treatment. CONCLUSION: Patients treated with PL epidurals
      reported significant improvements in pain, exceeded the minimal clinically
      important difference (MCID) for FRI, and reported subjective improvement through
      2-year follow-up. PL may be a promising substitute for corticosteroid.

PMID- 29177633
TI  - Osteoporosis is associated with increased risk for benign paroxysmal positional
      vertigo: a nationwide population-based study.
AB  - : Recent evidence has indicated that osteoporosis is a risk factor for benign
      paroxysmal positional vertigo (BPPV). This large population-based study
      demonstrated that patients with osteoporosis had a 1.82-fold higher risk of
      developing BPPV than those without osteoporosis through the use of the Taiwan
      National Health Insurance Research Database. PURPOSE: Benign paroxysmal
      positional vertigo (BPPV) is one of the most frequent causes of vertigo.
      Osteoporosis reflects a homeostatic imbalance in the rate of bone turnover, with
      the rate of bone resorption exceeding that of bone formation. Recent evidence has
      indicated that osteoporosis is a risk factor for BPPV. We aimed to validate the
      risk of BPPV in osteoporotic patients through a nationwide, population-based,
      cohort study. METHODS: Patients treated for osteoporosis were identified from
      entries made in the Taiwan National Health Insurance Research Database (NHIRD)
      between 2000 and 2013. Each osteoporosis patient was age- and sex-matched with
      four randomly selected subjects without osteoporosis. We compared the incidence
      rates of BPPV in the two cohorts (with and without osteoporosis) and identified
      risk factors. RESULTS: We identified 6649 osteoporosis patients and 26,596 match
      controls. According to the incidence of BPPV among the two groups, patients with
      osteoporosis were found to have a 1.82-fold higher risk of developing BPPV than
      those without osteoporosis. The incidence rate ratio (IRR) between osteoporotic
      patients and the control cohort was 2.0 (p < 0.001). CONCLUSIONS: This large
      population-based study demonstrated that patients with osteoporosis were
      associated with an increased risk for BPPV. The results of this study provide
      some insight into the management of BPPV.

PMID- 29177634
TI  - Endoscopic ultrasound (EUS) elastography and contrast enhanced EUS in groove
      pancreatitis.
AB  - We report for the first time the findings on endoscopic ultrasound elastrography
      and contrast enhanced EUS in a patient with groove pancreatitis.

PMID- 29177635
TI  - The ArlRS two-component system is a regulator of Staphylococcus aureus-induced
      endothelial cell damage.
AB  - Staphylococcus aureus endovascular infections retain a high morbidity and
      mortality despite antibiotics and supportive care. The destruction of endothelial
      cells (ECs) is a critical step in the pathogenesis of S. aureus endovascular
      infections. In order to better understand S. aureus-induced EC damage, we
      systematically screened a collection of two-component regulatory system mutants
      of methicillin-resistant S. aureus (MRSA) USA300 strain JE2 for damage induction
      in human umbilical vein ECs (HUVECs). This screen revealed that the two-component
      regulatory system ArlRS is required for maximum damage: arlRS inactivation leads
      to a > 70% reduction in damage. In a different genetic S. aureus background
      (RN6390, MSSA strain) arlRS inactivation had a smaller but also significant
      effect on EC damage. In both strains, the reduction in EC damage was accompanied
      by a significant reduction in internalization. In conclusion, we determined a
      novel role of ArlRS in S. aureus-induced EC damage, which will help to better
      understand the pathogenesis of S. aureus endovascular infection.

PMID- 29177636
TI  - Sequence Analysis and Comparative Bioinformatics Study of Camelysin Gene (calY)
      Isolated from Bacillus thuringiensis.
AB  - Bacillus strains have been widely used for the production of fibrinolytic enzymes
      having role in the treatment of cardiovascular disorders. Purification and
      overproduction of such enzymes has increased their usage in medical fields
      including metalloproteinases with the ability to degrade extracellular matrix
      (ECM). Camelysin, a neutral metalloproteinase has been isolated from different
      species of bacteria like Bacillus cereus, Bacillus anthracis, and Bacillus
      thuringiensis with fibrinolytic, collagenolytic and actin degradation activity.
      This project successfully demonstrated the presence of 734-bp coding DNA sequence
      (CDS) encoding a 20.72331 kDa camelysin gene in local strain of Bacillus
      thuringiensis containing a signal peptide with cleavage site between residues 19
      and 20. The sequence was submitted to GenBank (KT023597) and the sequence showed
      high homology with the camelysin protein of closely related Bacillus species. The
      alignment of related proteins through ClustalW displayed difference of four amino
      acids ("Q" replaced by "P" at position 169 and at position 182-184, "NQE"
      replaced by "HLK") in the isolated protein. Comparison including structural and
      functional analysis of camelysin sequences isolated from different Bacillus
      species was carried out using different bioinformatics tools and software. The
      information would help in better understanding the properties of camelysin
      protein and its role in pathogenicity and clinical treatments.

PMID- 29177637
TI  - Inappropriate claims from non-equivalent medications in osteoarthritis: a
      position paper endorsed by the European Society for Clinical and Economic Aspects
      of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).
AB  - Osteoarthritis (OA) is a progressive joint disease, that occurs frequently in the
      aging population and is a major cause of disability worldwide. Both glucosamine
      and chondroitin are biologically active molecules that are substrates for
      proteoglycan, an essential component of the cartilage matrix. Evidence supports
      the use of glucosamine and chondroitin as symptomatic slow-acting drugs for
      osteoarthritis (SYSADOAs) with impact on OA symptoms and disease-modifying
      effects in the long term. Glucosamine and chondroitin are administered in
      exogenous form as a sulfate salt and multiple formulations of these agents are
      available, both as prescription-grade products and nutritional supplements.
      However, while all preparations may claim to deliver a therapeutic level of
      glucosamine or chondroitin not all are supported by clinical evidence. Only
      patented crystalline glucosamine sulfate (pCGS) is shown to deliver consistently
      high glucosamine bioavailability and plasma concentration in humans, which
      corresponds to demonstrated clinical efficacy. Similarly, clinical evidence
      supports only the pharmaceutical-grade chondroitin sulfate. The European Society
      for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and
      Musculoskeletal Diseases (ESCEO) advocates, through careful consideration of the
      evidence base, that judicious choice of glucosamine and chondroitin formulation
      is essential to maximize clinical benefit, patient adherence and satisfaction
      with treatment. In future, the ESCEO recommends that complex molecules with
      biological activity such as pCGS may be treated as "biosimilars" akin to the
      European Medicines Agency guidance on biological medicinal products. It seems
      likely that for all other complex molecules classed as SYSADOAs, the
      recommendation to use only formulations clearly supported by the evidence-base
      should apply.

PMID- 29177638
TI  - The Ferroxidase Hephaestin But Not Amyloid Precursor Protein is Required for
      Ferroportin-Supported Iron Efflux in Primary Hippocampal Neurons.
AB  - Iron efflux in mammalian cells is mediated by the ferrous iron exporter
      ferroportin (Fpn); Fpn plasma membrane localization and function are supported by
      a multicopper ferroxidase and/or the soluble amyloid precursor protein (sAPP).
      Fpn and APP are ubiquitously expressed in all cell types in the central nervous
      system including neurons. In contrast, neuronal ferroxidase(s) expression has not
      been well characterized. Using primary cultures of hippocampal neurons, we
      examined the molecular mechanism of neuronal Fe efflux in detail. Developmental
      increases of Fpn, APP, and the ferroxidase hephaestin (Hp) were observed in
      hippocampal neurons. Iron efflux in these neurons depended on the level of Fpn
      localized at the cell surface; as noted, Fpn stability is supported by
      ferroxidase activity, an enzymatic activity that is required for Fe efflux. Iron
      accumulation increases and iron efflux decreases in Hp knockout neurons. In
      contrast, suppression of endogenous APP by RNAi knockdown does not affect surface
      Fpn stability or Fe efflux. These data support the model that the neuronal
      ferroxidase Hp plays a unique role in support of Fpn-mediated Fe efflux in
      primary hippocampal neurons. Our data also demonstrate that Hp ferroxidase
      activity relies on copper bioavailability, which suggests neuronal iron
      homeostasis will be modulated by cellular copper status.

PMID- 29177639
TI  - Referential and Non-referential Uses of the Third Person Pronominal Subject in
      Spanish.
AB  - This paper studies the role of two different types of motivation that have been
      proposed to explain the use of subject personal pronouns in Spanish, namely their
      function as indications for the addressee to identify the subject's referent, and
      their suitability for expressing informational values such as contrastiveness or
      focus. This study focuses exclusively on third-person forms and relies on
      conversational data. The distribution of third-person pronouns is analysed
      combining qualitative and quantitative approaches. It will be argued that the
      informational and referential properties of subject personal pronouns are by
      themselves insufficient to account for their expression, their occurrence
      depending crucially on their activation through the previous use of units of the
      same type.

PMID- 29177640
TI  - Heat stress alters genome-wide profiles of circular RNAs in Arabidopsis.
AB  - KEY MESSAGE: 1599 novel circRNAs and 1583 heat stress-specific circRNAs were
      identified in Arabidopsis. Heat stress enhanced accumulation of circRNAs
      remarkably. Heat stress altered the sizes of circRNAs, numbers of circularized
      exons and alterative circularization events. A putative circRNA-mediated ceRNA
      networks under heat stress was established. Heat stress retards plant growth and
      destabilizes crop yield. The noncoding RNAs were demonstrated to be involved in
      plant response to heat stress. As a newly-characterized class of noncoding RNAs,
      circular RNAs (circRNAs) play important roles in transcriptional and post
      transcriptional regulation. A few recent investigations indicated that plant
      circRNAs were differentially expressed under abiotic stress. However, little is
      known about how heat stress mediates biogenesis of circRNAs in plants. Here, we
      uncovered 1599 previously-unknown circRNAs and 1583 heat-specific circRNAs, by
      RNA-sequencing and bioinformatic analysis. Our results indicated that much more
      circRNAs were expressed under heat stress than in control condition. Besides,
      heat stress also increased the length of circRNAs, the quantity of circularized
      exons, and alternative circularization events. Moreover, we observed a positive
      correlation between expression patterns of some circRNAs and their parental
      genes. The prediction of ceRNA (competing endogenous RNA) networks indicated that
      differentially-expressed circRNAs could influence expression of many important
      genes, that participate in response to heat stress, hydrogen peroxide, and
      phytohormone signaling pathways, by interacting with the corresponding microRNAs.
      Together, our observations indicated that heat stress had great impacts on the
      biogenesis of circRNAs. Heat-induced circRNAs might participate in plant response
      to heat stress through the circRNA-mediated ceRNA networks.

PMID- 29177642
TI  - Three coexisting lymphomas in a single patient: composite lymphoma derived from a
      common germinal center B-cell precursor and unrelated discordant lymphoma.
AB  - Composite lymphoma (CL) is a rare disorder defined as the coexistence of two or
      more distinct lymphoma subtypes at a single anatomic site. Discordant lymphoma
      (DL), which is the simultaneous occurrence of two or more distinct lymphoma
      subtypes at different sites, is also rare. CL complicated with DL involving three
      distinct subtypes of lymphoma in the same patient is an extremely rare disease.
      Clonal relationships in CL and DL are commonly investigated by molecular analysis
      using mutational status with t(14;18)BCL2/IgH translocation and immunoglobulin
      heavy chain variable-region (IgVH) gene rearrangement. A 73-year-old woman was
      admitted to our hospital with systemic lymphadenopathy and was initially
      diagnosed with diffuse large B-cell lymphoma based on pathological features of
      the biopsied esophageal tumor. However, the results of inguinal lymph node biopsy
      led to a revised pathological diagnosis CL consisting of Hodgkin lymphoma and
      follicular lymphoma. Three distinct coexisting lymphomas were identified in this
      individual patient. Molecular analysis revealed CL derived from common germinal
      center B-cell precursors, while clonal relationship between CL and DL was not
      clarified. This case suggests a mechanism underlying B-cell lymphoma pathogenesis
      involving two pivotal somatic mutations, t(14;18)BCL2/IgH translocation and IgVH
      rearrangement.

PMID- 29177641
TI  - Prolactinoma through the female life cycle.
AB  - Prolactinomas are the most common secretory pituitary adenoma. They typically
      occur in women in the 3rd-6th decade of life and rarely in the pediatric
      population or after menopause. Most women present with irregular menses and/or
      infertility. Dopamine (DA) agonists, used in their treatment, are safe during
      pregnancy, but in most cases are discontinued at conception with close monitoring
      for signs or symptoms of tumor growth. Breastfeeding is safe postpartum, provided
      there was no significant growth during pregnancy. Some women will experience
      normalization of prolactin levels postpartum. Menopause may also decrease
      prolactin levels and even those with macroprolactinomas may consider
      discontinuing their DA agonist with close follow-up. Prolactinomas may be
      associated with decreased quality of life scores in women, and play a role in
      bone health and cardiovascular risk factors. This review discusses the current
      literature and clinical understanding of prolactinomas throughout the entirety of
      the female life cycle.

PMID- 29177643
TI  - Iron overload in myelodysplastic syndromes (MDS).
AB  - Iron overload (IOL) starts to develop in MDS patients before they become
      transfusion-dependent because ineffective erythropoiesis suppresses hepcidin
      production in the liver and thus leads to unrestrained intestinal iron uptake.
      However, the most important cause of iron overload in MDS is chronic transfusion
      therapy. While transfusion dependency by itself is a negative prognostic factor
      reflecting poor bone marrow function, the ensuing transfusional iron overload has
      an additional dose-dependent negative impact on the survival of patients with
      lower risk MDS. Cardiac dysfunction appears to be important in this context, as a
      consequence of chronic anemia, age-related cardiac comorbidity, and iron
      overload. Another potential problem is iron-related endothelial dysfunction.
      There is some evidence that with increasing age, high circulating iron levels
      worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate
      bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal
      cells as well a hematopoietic cells, particularly erythroid precursors. Patient
      series and clinical trials have shown that the iron chelators deferoxamine and
      deferasirox can improve hematopoiesis in a minority of transfusion-dependent
      patients. Analyses of registry data suggest that iron chelation provides a
      survival benefit for patients with MDS, but data from a prospective randomized
      clinical trial are still lacking.

PMID- 29177644
TI  - Pharmacokinetic Analysis of Four Bioactive Iridoid and Secoiridoid Glycoside
      Components of Radix Gentianae Macrophyllae and Their Synergistic Excretion by
      HPLC-DAD Combined with Second-Order Calibration.
AB  - An HPLC-DAD method combined with second-order calibration based on the
      alternating trilinear decomposition (ATLD) algorithm with the aid of region
      selection was developed to simultaneously and quantitatively characterize the
      synergistic relationships and cumulative excretion of the four bioactive
      ingredients of Radix Gentianae Macrophyllae in vivo. Although the analytes
      spectra substantially overlapped with that of the biological matrix, the
      overlapping profiles between analytes and co-eluting interferences can be
      successfully separated and accurately quantified by the ATLD method on the basis
      of the strength of region selection. The proposed approach not only determined
      the content change but also revealed the synergistic relationships and the
      cumulative excretion in vivo of the four ingredients in urine and feces samples
      collected at different excretion time intervals. In addition, several statistical
      parameters were employed to evaluate the accuracy and precision of the method.
      Quantitative results were confirmed by HPLC-mass spectrometry. Satisfactory
      results indicated that the proposed approach can be utilized to investigate the
      pharmacokinetics of Radix Gentianae Macrophyllae excretion in vivo.

PMID- 29177645
TI  - Ledipasvir-Sofosbuvir for 8 Weeks in Non-Cirrhotic Patients with Previously
      Untreated Genotype 1 HCV Infection +/- HIV-1 Co-Infection.
AB  - : BACKGROUND AND OBJECTIVES: The efficacy of < 12 weeks of hepatitis C virus
      (HCV) treatment in patients co-infected with HCV and human immunodeficiency virus
      type 1 (HIV-1) has not been established. We assessed the efficacy and safety of
      ledipasvir-sofosbuvir for 8 weeks in HCV mono-infected and HCV/HIV-1 co-infected
      patients. METHODS: We enrolled patients mono-infected with genotype 1 HCV or co
      infected with HCV and HIV-1 who were HCV treatment-naive and did not have
      cirrhosis. HCV/HIV-1 co-infected patients were either not receiving
      antiretroviral treatment and had a CD4 T-cell count > 500 cells/mm3 or were
      receiving a protocol-approved antiretroviral regimen for >= 8 weeks (or >= 6
      months for abacavir-containing regimens) and had HIV-1 RNA < 50 copies/mL and a
      CD4 T-cell count > 200 cells/mm3. Patients received ledipasvir-sofosbuvir (90/400
      mg) once daily for 8 weeks. The primary efficacy endpoint was sustained virologic
      response 12 weeks after treatment discontinuation (SVR12). RESULTS: The SVR12
      rate was 100% (67/67) for HCV mono-infected patients and 97% (57/59) for HCV/HIV
      1 co-infected patients. Two patients relapsed by the week 4 post-treatment visit.
      Overall, the most common adverse events were headache (52%) and upper abdominal
      pain (26%). There were no serious adverse events or treatment discontinuations
      due to adverse events. No HCV/HIV-1 co-infected patients receiving antiretroviral
      treatment experienced HIV virologic rebound, and no clinically meaningful changes
      in CD4 T-cell counts were observed in any co-infected patient. CONCLUSIONS: Non
      cirrhotic, treatment-naive patients with genotype 1 HCV mono-infection and
      HCV/HIV-1 co-infection achieved high rates of SVR12 with 8 weeks of treatment
      with ledipasvir/sofosbuvir. ClinicalTrials.gov identifier: NCT02472886.

PMID- 29177646
TI  - Longitudinal patterns of potentially inappropriate prescribing in early old-aged
      people.
AB  - PURPOSE: It is contentious whether potentially inappropriate prescribing (PIP) is
      predominantly a phenomenon of late life or whether it has its origins in early
      old age. This study examined the pattern of PIP in an early old-aged population
      over 5 years. METHODS: Secondary data analysis of a population-based primary care
      cohort, of patients aged 60-74 years. Medication data were extracted from
      electronic patient records in addition to information on comorbidities and
      demographics. Explicit START criteria (PPOs) and STOPP criteria (PIMs) were used
      to identify PIP. Generalised estimating equations were used to describe trends in
      PIP over time and adjusted for age, gender and number of medicines. RESULTS: A
      total of 978 participants (47.8%) aged 60-74 years were included from the cohort.
      At baseline, PPOs were detected in 31.2% of patients and PIMs were identified in
      35.6% at baseline. Prevalence of PPOs and PIMs increased significantly over time
      (OR 1.08, 95% CI 1.07; 1.09 and OR 1.04, 95% CI 1.0; 1.06, respectively). A
      higher number of medicines and new diagnoses were associated with the increasing
      trend in both PPO and PIM prevalence observed over time, independent of PPOs and
      PIMs triggered by drug combinations. CONCLUSIONS: Potentially inappropriate
      prescribing is highly prevalent among early old-aged people in primary care and
      increases as they progress to more advanced old age, suggesting that routine
      application of STOPP/START criteria in this population would significantly
      improve medication appropriateness.

PMID- 29177647
TI  - Targeted Deletion of Hsf1, 2, and 4 Genes in Mice.
AB  - Heat shock transcription factors (Hsfs) regulate transcription of heat shock
      proteins as well as other genes whose promoters contain heat shock elements
      (HSEs). There are at least five Hsfs in mammalian cells, Hsf1, Hsf2, Hsf3, Hsf4,
      and Hsfy (Wu, Annu Rev Cell Dev Biol 11:441-469, 1995; Morimoto, Genes Dev
      12:3788-3796, 1998; Tessari et al., Mol Hum Repord 4:253-258, 2004; Fujimoto et
      al., Mol Biol Cell 21:106-116, 2010; Nakai et al., Mol Cell Biol 17:469-481,
      1997; Sarge et al., Genes Dev 5:1902-1911, 1991). To understand the physiological
      roles of Hsf1, Hsf2, and Hsf4 in vivo, we generated knockout mouse lines for
      these factors (Zhang et al., J Cell Biochem 86:376-393, 2002; Wang et al.,
      Genesis 36:48-61, 2003; Min et al., Genesis 40:205-217, 2004). Numbers of other
      laboratories have also generated Hsf1 (Xiao et al., EMBO J 18:5943-5952, 1999;
      Sugahara et al., Hear Res 182:88-96, 2003), Hsf2 (McMillan et al., Mol Cell Biol
      22:8005-8014, 2002; Kallio et al., EMBO J 21:2591-2601, 2002), and Hsf4 (Fujimoto
      et al., EMBO J 23:4297-4306, 2004) knockout mouse models. In this chapter, we
      describe the design of the targeting vectors, the plasmids used, and the
      successful generation of mice lacking the individual genes. We also briefly
      describe what we have learned about the physiological functions of these genes in
      vivo.

PMID- 29177648
TI  - Role of Heat Shock Factors in Stress-Induced Transcription.
AB  - Heat shock proteins (HSP) are rapidly induced after stresses such as heat shock
      and accumulate at high concentrations in cells. HSP induction involves primarily
      a family of heat shock transcription factors (HSF) that bind the heat shock
      elements of the HSP genes and mediate transcription in trans. We discuss methods
      for the study of HSP binding to HSP promoters and the consequent increases in HSP
      gene expression in vitro and in vivo.

PMID- 29177649
TI  - Monitoring of the Heat Shock Response with a Real-Time Luciferase Reporter.
AB  - The heat shock response (HSR) is a cellular mechanism for counteracting acute
      proteotoxic stress. In eukaryotes, transcriptional activation of the HSR is
      regulated by heat shock factor 1 (HSF1). Activation of HSF1 induces the
      expression of heat shock proteins (HSPs) that function as molecular chaperones to
      fold and maintain the three-dimensional structure of misfolded proteins. The
      regulation of the degree and duration of the HSR is controlled by multiple
      biochemical mechanisms that include posttranslational modification of HSF1 and
      numerous protein-protein interactions. In this chapter, we describe a method to
      evaluate the activation and deactivation of the HSR at the transcriptional level
      using a short half-life luciferase reporter assay. This assay can be used to
      further characterize the HSR or as a screen for small-molecule inducers,
      amplifiers, or repressors.

PMID- 29177650
TI  - Quantitative Profiling of Chaperone/Client Interactions with LUMIER Assay.
AB  - Chaperones associate with hundreds or thousands of diverse client proteins and
      regulate their function. Chaperone/client interactions are generally very
      transient and involve a highly orchestrated assembly and disassembly of
      regulatory co-factors. This poses specific challenges for identifying and
      characterizing these interactions in a scalable and sensitive manner. LUMIER
      assay, which takes advantage of the high sensitivity and linear range of
      luminescence-based detection, has proven to be an ideal assay to quantitatively
      profile chaperone/client interactions in a high-throughput manner. This article
      provides step-by-step instructions for quantitatively profiling these
      interactions with LUMIER.

PMID- 29177651
TI  - Measurement of Chaperone-Mediated Effects on Polyglutamine Protein Aggregation by
      the Filter Trap Assay.
AB  - The formation of aggregates by polyglutamine-containing (polyQ) proteins in
      neurons is a key to the pathogenesis of several progressive neurodegenerative
      diseases such as Huntington's disease (HD) spinocerebellar ataxias (SCAs), and
      spinal and bulbar muscular atrophy (SBMA). In order to study whether the members
      of the heat shock protein (HSP) families, by virtue of their molecular chaperone
      activity, can inhibit the formation of polyQ aggregates, we developed a cell
      culture model expressing the GFP tagged fragment of exon1 of the huntingtin gene
      with an expanded polyQ chain and tetracycline inducible chaperones. Expression of
      mutated Huntington's protein leads to the formation of 2% SDS insoluble high
      molecular weight polyQ aggregates that are retarded on a cellulose acetate
      membrane in the so-called filter trap assay (FTA). This chapter explains in
      detail the protocols of the FTA and how it can be a useful tool to study the
      effect of HSPs or their functional mutants on aggregation of polyglutamine
      proteins. Moreover, the assay is useful to investigate how externally added polyQ
      peptides can act as nucleation seeds for internally expressed polyQ proteins.

PMID- 29177652
TI  - Fluorescent-Linked Enzyme Chemoproteomic Strategy (FLECS) for Identifying HSP70
      Inhibitors.
AB  - Activation of the heat shock response, and in particular upregulation of stress
      inducible Hsp70, herein referred to as Hsp70i, in newly transformed cells,
      appears to protect against protein damaging stimuli, induction of premature
      oncogene-induced terminal senescence (OIS), and apoptosis, thereby enabling tumor
      initiation and progression to an aggressive phenotype. Expressed at very low or
      undetectable levels in normal tissue, the cytoprotective effects of Hsp70i appear
      to be mediated through its activity as a molecular chaperone allowing proper
      folding of mutated proteins, and by blocking cell signaling pathways that
      regulate OIS and apoptosis. Identification of small-molecule inhibitors selective
      for Hsp70i could provide new therapeutic tools for cancer treatment. However,
      identification of selective inhibitors of Hsp70i has proven challenging largely
      because of the affinity of the protein for ATP. Additionally, its chaperone
      functions do not lend the protein amenable to traditional enzymatic high
      throughput screens. Here, we describe the use of fluorescence-linked enzyme
      chemoproteomic strategy (FLECS) to identify Hsp70i inhibitors. The FLECS assay is
      a simple binding assay that enables proteins tagged with fluorophors to be
      rapidly and quantitative screened against small-molecule libraries. We show
      several case history examples of the methodology that led to the discovery of the
      Fatty acid synthase inhibitor, FASNALL, the DAPK3 inhibitor HS38, and HS72, an
      allosteric inhibitor selective for Hsp70i.

PMID- 29177653
TI  - A High-Throughput Screen for Inhibitors of the Hsp90-Chaperone Machine.
AB  - Hsp90 has emerged as a key chemotherapeutic target for the development of drugs
      for the treatment of cancer and neurodegenerative diseases. The shortcomings of
      many of the Hsp90 inhibitors that have made it to clinical trials have bolstered
      the need to identify new lead compounds with superior properties. Here, we
      describe a high-throughput screen for the identification of Hsp90 inhibitors
      based on the refolding of thermally denatured firefly luciferase.

PMID- 29177654
TI  - Primary Colorectal Cells Culture as a Translational Research Model.
AB  - Preclinical studies are an essential stage for any pharmacological agent hoping
      to make its way into clinical trials. An ideal preclinical model that can
      accurately predict clinical response does not exist and the best that the
      scientific community have at the moment is to select the most relevant study
      model pertaining to the disease of interest from those available, which includes:
      cell lines, animal models, and even in-silico methodology. Currently, there is a
      huge gap between preclinical and clinical trial results, indicating that there is
      much room for improvement in developing a better model to bridge the
      translational gap.

PMID- 29177655
TI  - Cell Death and Survival Assays.
AB  - Heat shock proteins are well-known protectors from cell death. Cell death (in
      particular, apoptosis and necrosis) is accompanied by certain hallmarks
      manifested as specific alterations in cellular membranes, cytoplasm, nucleus, and
      mitochondria. Some of those hallmarks are easily detectable in situ and,
      therefore, they can be applied for the assessment of dying or dead cells. In
      turn, there are also signs of viable cells that include such features as normal
      functioning of their membranes and organelles, ability to proliferate, etc. This
      chapter describes several convenient methods for quantification of dead
      (apoptotic and necrotic) cells as well as methods for assessment of viable cells.
      We describe in detail methods of annexin V/propidium iodide (PI) staining, TUNEL
      assay, Hoechst/PI staining, caspase activation, MTS tetrazolium, lactate
      dehydrogenase (LDH) release, colony formation, and senescence assays, with the
      principles, advantages, and drawbacks of each technique.

PMID- 29177656
TI  - Detecting the Potential Pharmacological Synergy of Drug Combination by Viability
      Assays In Vitro.
AB  - Heat shock protein 90 (HSP90) is a molecular chaperone necessary for the folding
      and proper function of multiple "client" proteins. HSP90 is involved in numerous
      biological processes and is critical to maintain proteostasis and to protect the
      cells from potentially harmful environmental stresses such as heat. However, in
      cancer, the role of HSP90, and other molecular chaperones, is corrupted as many
      of HSP90 clients are kinases and transcription factors whose aberrant activation
      or mutation drives tumor growth. Thus, developing a polytherapy, or combination
      therapy, that includes an HSP90 inhibitor in addition to targeting an oncogene or
      oncogenic pathway is an appealing therapeutic approach. This protocol will
      provide detailed methods on how to assess the potential synergy of polytherapy by
      viability assays in vitro.

PMID- 29177657
TI  - Proteomic Profiling of Hsp90 Inhibitors.
AB  - Mass spectrometry assays demonstrate that Hsp90 inhibitors alter the expression
      of approximately one-quarter of the assayable proteome in mammalian cells. These
      changes are extraordinarily robust and reproducible, making "proteomics
      profiling" the gold standard for validating the effects of new Hsp90 inhibitors
      on cultured cells. Proteomics assays can also suggest novel hypotheses regarding
      drug mechanisms. To assist investigators in adopting this approach, this Chapter
      provides detailed protocols for conducting simple proteomics assays of Hsp90
      inhibition. The protocols present a robust label-free approach that utilizes pre
      fractionation of protein samples by SDS-PAGE, thereby providing reasonably good
      penetration into the proteome while addressing common issues with sample quality.
      The actual programming and operation of liquid chromatography-tandem mass
      spectrometers is not covered, but expectations for achievable performance are
      discussed, as are alternative approaches, common challenges, and software for
      data analysis.

PMID- 29177658
TI  - Analysis of HspB1 (Hsp27) Oligomerization and Phosphorylation Patterns and Its
      Interaction with Specific Client Polypeptides.
AB  - Human HspB1 (also denoted as Hsp27) belongs to the family of small (or stress)
      proteins (sHsps). The family, which contains ten members including alphaA,B
      crystallin polypeptides, is characterized by a conserved C-terminal alpha
      crystallin domain and molecular weights ranging from 20 to 40 kDa. Here,
      procedures are described for analyzing the dynamic oligomerization and
      phosphorylation patterns of HspB1 in cells exposed to different environments.
      Changes in the structural organization of HspB1 can reprogram its interaction
      with specific partner/client polypeptides. Methods are presented to analyze these
      interactions using tissue culture cells genetically modified to express different
      levels of this protein. In addition, the laboratory approaches presented here
      could be used to test the nine other human sHsp members as well as sHsps from
      other species.

PMID- 29177659
TI  - Nucleotide Exchange Factors for Hsp70 Chaperones.
AB  - The ATPase cycle of Hsp70 chaperones controls their transient association with
      substrates and thus governs their function in protein folding. Nucleotide
      exchange factors (NEFs) accelerate ADP release from Hsp70, which results in
      rebinding of ATP and release of the substrate, thereby regulating the lifetime of
      the Hsp70-substrate complex. This chapter describes several methods suitable to
      study NEFs of Hsp70 chaperones. On the one hand, steady-state ATPase assays
      provide information on how the NEF influences progression of the Hsp70 through
      the entire ATPase cycle. On the other hand, nucleotide release can be measured
      directly using labeled nucleotides, which enables identification and further
      characterization of NEFs.

PMID- 29177660
TI  - Determination of Hsp90 Activity Through Activation of Glucocorticoid Receptors in
      Yeast.
AB  - Heat shock protein 90 (Hsp90) is an essential regulator of cellular function
      through activation of so-called client proteins. Hsp90 is currently a target for
      potential anti-cancer therapeutics. Assaying for defects in Hsp90 using budding
      yeast (Saccharomyces cerevisiae) is possible and efficient due to the high
      conservation between the human and yeast Hsp90 systems. Here, we present a method
      for the determination of Hsp90 activity indirectly through the activation of
      exogenously expressed glucocorticoid receptor, a natural client protein of Hsp90.

PMID- 29177661
TI  - Bacterial Hsp90 ATPase Assays.
AB  - Bacterial Hsp90 is an ATP-dependent molecular chaperone involved in protein
      remodeling and activation. The E. coli Hsp90, Hsp90Ec, collaborates in protein
      remodeling with another ATP-dependent chaperone, DnaK, the E. coli Hsp70. Both
      Hsp90Ec and DnaK hydrolyze ATP and client (substrate) proteins stimulate the
      hydrolysis. Additionally, ATP hydrolysis by the combination of Hsp90Ec and DnaK
      is synergistically stimulated in the presence of client (substrate). Here, we
      describe two steady-state ATPase assays used to monitor ATP hydrolysis by Hsp90Ec
      and DnaK as well as the synergistic stimulation of ATP hydrolysis by the
      combination of Hsp90Ec and DnaK in the presence of a client (substrate). The
      first assay is a spectrophotometric assay based on enzyme-coupled reactions that
      utilize the ADP formed during ATP hydrolysis to oxidize NADH. The second assay is
      a more sensitive method that directly quantifies the radioactive inorganic
      phosphate released following the hydrolysis of [gamma-33P] ATP or [gamma-32P]
      ATP.

PMID- 29177662
TI  - Detecting Posttranslational Modifications of Hsp90.
AB  - The molecular chaperone Heat Shock Protein 90 (Hsp90) is essential in eukaryotes.
      Hsp90 chaperones proteins that are important determinants of multistep
      carcinogenesis. The chaperone function of Hsp90 is linked to its ability to bind
      and hydrolyze ATP. Co-chaperones as well as posttranslational modifications
      (phosphorylation, SUMOylation, and ubiquitination) are important for its
      stability and regulation of the ATPase activity. Both mammalian and yeast cells
      can be used to express and purify Hsp90 and also detect its posttranslational
      modifications by immunoblotting.

PMID- 29177663
TI  - Chromatin Immunoprecipitation (ChIP) of Heat Shock Protein 90 (Hsp90).
AB  - Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a widely used
      technique for genome-wide mapping of protein-DNA interactions and epigenetic
      marks in vivo. Recent studies have suggested an important role of heat shock
      protein 90 (Hsp90) at chromatin. This molecular chaperone assists other proteins
      to acquire their mature and functional conformation and helps in the assembly of
      many complexes. In this chapter, we provide specific details on how to perform
      Hsp90 ChIP-seq from Drosophila Schneider (S2) cells. Briefly, the cells are
      simultaneously lyzed and reversibly cross-linked to stabilize protein-DNA
      interactions. Chromatin is prepared from isolated nuclei and sheared by
      sonication. Hsp90-bound loci are immunoprecipitated and the corresponding DNA
      fragments are purified and sequenced. The described approach revealed that Hsp90
      binds close to the transcriptional start site of around one-third of all
      Drosophila coding genes and characterized the role of the chaperone at chromatin.

PMID- 29177664
TI  - A Workflow Guide to RNA-seq Analysis of Chaperone Function and Beyond.
AB  - RNA sequencing (RNA-seq) is a powerful method of transcript analysis that allows
      for the sequence identification and quantification of cellular transcripts. RNA
      seq has many applications including differential gene expression (DE) analysis,
      gene fusion detection, allele-specific expression, isoform and splice variant
      quantification, and identification of novel genes. These applications can be used
      for downstream systems biology analyses such as gene ontology analysis to provide
      insights into cellular processes altered between biological conditions. Given the
      wide range of signaling pathways subject to chaperone activity as well as
      numerous chaperone functions in RNA metabolism, RNA-seq may provide a valuable
      tool for the study of chaperone proteins in biology and disease. This chapter
      outlines an example RNA-seq workflow to determine differentially expressed (DE)
      genes between two or more sample conditions and provides some considerations for
      RNA-seq experimental design.

PMID- 29177665
TI  - Computational Modeling of the Hsp90 Interactions with Cochaperones and Small
      Molecule Inhibitors.
AB  - Allosteric interactions of the molecular chaperone Hsp90 with a diverse array of
      cochaperones and client proteins, such as protein kinases and transcription
      factors, allow for efficient molecular communication in signal transduction
      networks. Deregulation of pathways involving these proteins is commonly
      associated with cancer pathologies and allosteric inhibition of oncogenic clients
      by targeting Hsp90 provides a powerful therapeutic strategy in cancer research.
      We review several validated computational approaches and tools used in the
      studies of the Hsp90 interactions with proteins and small molecules. These
      methods include experimentally guided docking to predict Hs90-protein
      interactions, molecular and binding free energy simulations to analyze Hsp90
      binding with small molecules, and structure-based network modeling to evaluate
      allosteric interactions and communications in the Hsp90 regulatory complexes.
      Through the lens of allosteric-centric view on Hsp90 function and regulation, we
      discuss newly emerging computational tools that link protein structure modeling
      with biophysical simulations and network-based systems biology approaches.

PMID- 29177666
TI  - Computational Analysis of the Chaperone Interaction Networks.
AB  - We provide computational protocols to identify chaperone interacting proteins
      using a combination of both physical (protein-protein) and genetic (gene-gene or
      epistatic) interaction data derived from the published large-scale proteomic and
      genomic studies for the budding yeast Saccharomyces cerevisiae. Using these
      datasets, we discuss bioinformatic analyses that can be employed to build
      comprehensive high-fidelity chaperone interaction networks. Given that many
      proteins typically function as complexes in the cell, we highlight various step
      wise approaches for combining both the genetic and physical interaction datasets
      to decipher intra- and inter-connections for distinct chaperone- and non
      chaperone-containing complexes in the network. Together, these informatics
      procedures will aid in identifying protein complexes with distinctive functional
      specializations in the cell that yield a very broad and diverse set of
      interactions. The described procedures can also be leveraged to datasets from
      other eukaryotes, including humans.

PMID- 29177667
TI  - Immunohistochemistry of Human Hsp60 in Health and Disease: From Autoimmunity to
      Cancer.
AB  - Hsp60 (also called Cpn60) is a chaperonin with essential functions for cell
      physiology and survival. Additionally, its involvement in the pathogenesis of a
      variety of diseases (e.g., some autoimmune disorders and cancer) is becoming
      evident with new research. For example, the distribution and levels of Hsp60 in
      cells and tissues have been found altered in many pathologic conditions, and the
      significance of these alterations is being investigated in a number of
      laboratories. The aim of this ongoing research is to determine the meaning of
      these Hsp60 alterations with regard to pathogenetic mechanisms, diagnosis,
      classification of lesions, and assessing prognosis and response to
      treatment.Hsp60 occurs in the mitochondria, i.e., its typical residence according
      to classic knowledge, and also in other locales, such as the cytosol, the cell
      membrane, the intercellular space, and biological fluids (e.g., blood and
      cerebrospinal fluid). Detection and quantitative determinations in all these
      locations are becoming essential components of laboratory pathology in clinics
      and research. Consequently, immunohistochemistry targeting Hsp60 is also becoming
      essential for pathologists and researchers interested in disorders involving this
      chaperonin.In this chapter, we summarize some recent discoveries on the
      participation of Hsp60 in the pathogenesis of human diseases, and describe in
      detail how to perform immunohistochemical reactions for detecting the chaperonin,
      determining its location, and measuring its quantitative levels.

PMID- 29177668
TI  - Immunohistochemical and Flow Cytometric Analysis of Intracellular and Membrane
      Bound Hsp70, as a Putative Biomarker of Glioblastoma Multiforme, Using the
      cmHsp70.1 Monoclonal Antibody.
AB  - The major stress-inducible 70 kDa heat shock (stress) protein 70 (Hsp70) is
      frequently overexpressed in highly aggressive tumor cells and thus might serve as
      a tumor-specific biomarker of aggressive disease. We have previously shown that,
      in contrast to normal cells, tumor cells present Hsp70 on their plasma membrane.
      In order to elucidate the role of intracellular and membrane-bound Hsp70 as a
      potential tumor biomarker in glioblastoma multiforme, herein, we describe
      protocols for the staining of cytosolic Hsp70 in tumor formalin fixed paraffin
      embedded (FFPE) sections using immunohistochemistry, and for plasma membrane
      bound Hsp70 by multi-parametric flow cytometry using the cmHsp70.1 monoclonal
      antibody (mAb).

PMID- 29177669
TI  - Detection and Analysis of Extracellular Hsp90 (eHsp90).
AB  - Heat Shock Protein 90 (Hsp90) is a ubiquitous molecular chaperone that comprises
      about 1-3% of the total cellular protein. Over the last decade, Hsp90 has been
      detected and studied in the extracellular space (extracellular or eHsp90) of
      normal and neoplastic cells. Once outside the cell, eHsp90 has been shown to
      interact with extracellular client proteins and promote their stabilization and
      function. Cell conditioned media are routinely collected to detect and quantify
      eHsp90, and determine its interactions with extracellular clients. Finally,
      targeting specifically the eHsp90 with pharmacologic inhibitors or antibodies
      that are unable to cross the plasma membrane has been beneficial in inhibiting
      tumor cell motility and invasion.

PMID- 29177670
TI  - Molecular Chaperone Receptors.
AB  - Extracellular heat shock proteins (HSP) play important roles in cell signaling
      and immunity. Many of these effects are mediated by surface receptors expressed
      on a wide range of cell types. We have investigated the nature of such proteins
      by cloning candidate receptors into cells (CHO-K1) with the rare property of
      being null for HSP binding. Using this approach we have discovered that Hsp70
      binds avidly to at least two classes of receptors including: (1) c-type lectin
      receptors (CLR) and (2) scavenger receptors (SR). However, the structural nature
      of the receptor-ligand interactions is not clear at this time. Hsp70 can bind to
      LOX-1 (a member of both the CLR and SR), with the c-type lectin binding domain
      (CTLD) as well as the SR family members SREC-I and FEEL-1/CLEVER-1/STABILIN-1,
      which by contrast have arrays of EGF-like repeats in their extracellular domains.
      In this chapter we will discuss: (1) methods for discovery of HSP receptors, (2)
      approaches to the study of individual receptors in cells that contain multiple
      such receptors, and (3) methods for investigating HSP receptor function in vivo.

PMID- 29177672
TI  - A Novel Heat Shock Protein 70-based Vaccine Prepared from DC-Tumor Fusion Cells.
AB  - We have developed an enhanced molecular chaperone-based vaccine through rapid
      isolation of Hsp70 peptide complexes after the fusion of tumor and dendritic
      cells (Hsp70.PC-F). In this approach, the tumor antigens are introduced into the
      antigen processing machinery of dendritic cells through the cell fusion process
      and thus we can obtain antigenic tumor peptides or their intermediates that have
      been processed by dendritic cells. Our results show that Hsp70.PC-F has increased
      immunogenicity compared to preparations from tumor cells alone and therefore
      constitutes an improved formulation of chaperone protein-based tumor vaccine.

PMID- 29177671
TI  - Creation of Recombinant Chaperone Vaccine Using Large Heat Shock Protein for
      Antigen-Targeted Cancer Immunotherapy.
AB  - Large heat shock proteins (HSPs) or stress proteins, including Hsp110 and Grp170,
      are unique molecular chaperones with superior capability of shuttling tumor
      protein antigens into professional antigen-presenting cells, such as dendritic
      cells, for highly efficient cross-presentation and T cell priming. Reconstituted
      chaperone complexes of large HSP and tumor protein antigen have been demonstrated
      to generate a robust antigen-specific T lymphocyte response with therapeutic
      potency against multiple cancer types in preclinical models. Here, we describe
      the methods for preparing this recombinant chaperone complex vaccine and
      analyzing the vaccine-induced activation of antigen-specific T cells using in
      vitro and in vivo systems.

PMID- 29177673
TI  - Hsp70: A Cancer Target Inside and Outside the Cell.
AB  - Heat shock protein 70 (Hsp70) is the most ubiquitous stress-inducible chaperone.
      It accumulates in the cells in response to a wide variety of physiological and
      environmental insults including anticancer chemotherapy, thus allowing the cell
      to survive to lethal conditions. Intracellular Hsp70 is viewed as a
      cytoprotective protein. Indeed, this protein can inhibit key effectors of the
      apoptotic and autophagy machineries. In cancer cells, the expression of Hsp70 is
      abnormally high, and Hsp70 may participate in oncogenesis and in resistance to
      chemotherapy. In rodent models, Hsp70 overexpression increases tumor growth and
      metastatic potential. Depletion or inhibition of Hsp70 frequently reduces the
      size of the tumors and can even cause their complete involution. However, HSP70
      is also found in the extra-cellular space where it may signal via membrane
      receptors or endosomes to alter gene transcription and cellular function.
      Overall, Hsp70 extracellular function is believed to be immnunogenic and the term
      chaperokine to define the extracellular chaperones such as Hsp70 has been
      advanced. In this chapter the knowledge to date, as well as some emerging
      paradigms about the intra- and extra-cellular functions of Hsp70, are presented.
      The strategies targeting Hsp70 that are being developed in cancer therapy will
      also be discussed.

PMID- 29177674
TI  - Evidence for Hsp90 Co-chaperones in Regulating Hsp90 Function and Promoting
      Client Protein Folding.
AB  - Molecular chaperones are a diverse group of highly conserved proteins that
      transiently interact with partially folded polypeptide chains during normal
      cellular processes such as protein translation, translocation, and disassembly of
      protein complexes. Prior to folding or after denaturation, hydrophobic residues
      that are normally sequestered within a folded protein are exposed to the aqueous
      environment and are prone to aggregation or misfolding. Multiple classes of
      molecular chaperones, such as Hsp70s and Hsp40s, recognize and transiently bind
      polypeptides with exposed hydrophobic stretches in order to prevent misfolding.
      Other types of chaperones, such as Hsp90, have more specialized functions in that
      they appear to interact with only a subset of cellular proteins. This chapter
      focuses on the role of Hsp90 and partner co-chaperones in promoting the folding
      and activation of a diverse group of proteins with critical roles in cellular
      signaling and function.

PMID- 29177675
TI  - Clinical Evaluation and Biomarker Profiling of Hsp90 Inhibitors.
AB  - Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) have been in
      clinical development as anticancer agents since 1998. There have been 18 Hsp90
      inhibitors (Hsp90i) that have entered the clinic, all of which, though
      structurally distinct, target the ATP-binding Bergerat fold of the chaperone N
      terminus. Currently, there are five Hsp90 inhibitors in clinical trial and no
      approved drug in this class. One impediment to development of a clinically
      efficacious Hsp90 inhibitor has been the very low percentage of clinical trials
      that have codeveloped a predictive or pharmacodynamic marker of the anticancer
      activity inherent in this class of drugs. Here, we provide an overview of the
      clinical development of Hsp90 inhibitors, review the pharmacodynamic assays that
      have been employed in the past, and highlight new approaches to Hsp90 inhibitor
      clinical development.

PMID- 29177676
TI  - Extracranial extra-CNS spread of embryonal tumor with multilayered rosettes
      (ETMR): case series and systematic review.
AB  - BACKGROUND: Embryonal tumors with multilayered rosettes (ETMR) is a rare variant
      of embryonal tumor of infancy with nearly 200 cases reported in the literature.
      Leptomeningeal spread of this tumor is well known; however, extracranial
      metastasis has been sparsely reported in the literature. METHODS: Our study was
      divided into two sections: (1) We conducted a retrospective review of our patient
      series of ETMR and screened for patients with evidence of ETMR over the last 10
      years 2007-2017 at a single tertiary referral pediatric hospital, and (2) we
      conducted a systematic review according to PRISMA guidelines of all reported
      cases of ETMR to determine the incidence of extracranial metastasis and treatment
      paradigms. RESULTS: Here we report three cases of extracranial non-CNS spread of
      ETMR and conduct a systematic review of ETMR to improve our understanding of ETMR
      metastases and treatment paradigms. In our systematic review (n = 204), median
      overall survival was less than 1 year with 44.1% children surviving over 1 year.
      Previously, only five cases of extracranial metastasis of ETMR have been
      reported. CONCLUSIONS: Our case series (n = 3) and review demonstrate that these
      tumors may behave like soft tissue sarcomas and may be susceptible to tumor
      seeding through surgical manipulation or by CSF (ventriculoperitoneal shunt).
      Surgery for tumor recurrence may offer an improved local disease control, but
      preventative measures such as meticulous surgical resection may be necessary to
      reduce intraoperative contamination.

PMID- 29177677
TI  - Multibiomarker Responses of Juvenile Stages of Zebrafish (Danio rerio) to
      Subchronic Exposure to Polycyclic Musk Tonalide.
AB  - Synthetic polycyclic musks, widely used as additives in personal care products,
      are present in both biotic and abiotic matrices of the aquatic environment at
      concentrations of ng/l to ug/l. Although they are determined at comparatively low
      concentrations, these levels are biologically relevant and pose a significant
      growing risk as stressors to aquatic organisms. The purpose of our study was to
      evaluate the effects of 28-day-long exposure to polycyclic musk tonalide in
      zebrafish juvenile stages (Danio rerio) using selected biomarkers.
      Environmentally relevant concentrations of tonalide caused significant changes in
      selected enzyme activities in the experimental groups exposed to the highest
      concentrations. The activity of glutathione S-transferase and lipid peroxidation
      increased significantly (p < 0.05) after exposure to the highest concentration
      (50,000 ng/l) compared with the control. A similar trend was observed in catalase
      activity; there was a significant increase (p < 0.05) after exposure to two
      highest concentrations of tonalide (5000 and 50,000 ng/l). In addition, a
      statistically significant decrease (p < 0.05) in glutathione reductase activity
      was found in the lowest test concentration of tonalide (50 ng/l). None of the
      tested concentrations resulted in histopathological changes in liver, kidney,
      skin, or gill. Furthermore, no effects on body weight, body length, specific
      growth rate, and behavior were observed. Our results showed that tonalide
      exposure induced profound changes in the activities of antioxidant and
      detoxifying enzymes, such changes representing an adaptive response of the fish
      organism to tonalide toxicity.

PMID- 29177678
TI  - Enrichment and Bioavailability of Trace Elements in Soil in Vicinity of Railways
      in Japan.
AB  - This study focuses on the concentrations, distribution, pollution levels, and
      bioavailability of 12 trace elements in soils along 6 different railways in
      Japan. Three diesel powered railways and three electricity powered railways were
      chosen as target. Surface soils (< 3 cm) were collected in vicinity of railways
      for analysis. Digestion and extraction were performed before concentration and
      bioavailability analysis. Enrichment factor was applied to investigate
      contamination levels of selected elements. The mean concentrations of Cr, Co, Ni,
      Cu, Zn, Sn, and Pb in soil samples were higher than soil background value in
      Japan. Concentrations of trace elements in soils along different railway had
      different characteristics. Horizontal distribution of Cu, Zn, Cd, Sn, and Pb in
      soil samples showed obviously downtrend with distance along railways with high
      frequency. Concentrations of V, Mn, Fe, and Co were higher in soils along
      railways which pass through city center. According to principal component
      analysis and cluster analysis, concentrations of Cu, Zn, Sn, and Pb could be
      considered as the indicators of soil contamination level along electricity
      powered trains, whereas indicators along diesel powered trains were not clear.
      Enrichment factor analysis proved that operation of freight trains had impact on
      pollution level of Cr, Ni, and Cd. Bioavailability of Mn, Co, Zn, and Cd in soil
      along electricity-powered railways were higher, and bioavailability of Pb in
      railways located in countryside was lower. Thus, enrichment and bioavailability
      of trace elements can be indicators of railway-originated trace elements
      pollution in soil.

PMID- 29177680
TI  - Measuring the adhesion limit of fibronectin for fibroblasts with a narrow-gap
      rotational rheometer.
AB  - We study the adhesion limit of 3T6 fibroblasts, cultured in Dulbecco's modified
      Eagle's medium with 10% fetal bovine serum at 37  degrees C and 5% CO2, with a
      narrow-gap rotational rheometer in the parallel-disk configuration. Reducing the
      uncertainty in gap width to about 1 um allows studying the cells at narrow gaps,
      which enables to study the critical shear stress of the cells in low-viscous
      media. The adhesion limit on fibronectin-coated glass plates is determined as a
      function of concentration and adhesion time. We found that cells in groups have a
      tendency to detach at slightly higher shear stresses than single cells. Moreover,
      60 min after the settling phase are enough for the cells to adhere to the coated
      plate at maximum strength. We show that the setup may also be used for cells that
      are not adhered from suspension, but are grown directly on the substrate.

PMID- 29177679
TI  - Polygenic hazard score: an enrichment marker for Alzheimer's associated amyloid
      and tau deposition.
AB  - There is an urgent need for identifying nondemented individuals at the highest
      risk of progressing to Alzheimer's disease (AD) dementia. Here, we evaluated
      whether a recently validated polygenic hazard score (PHS) can be integrated with
      known in vivo cerebrospinal fluid (CSF) or positron emission tomography (PET)
      biomarkers of amyloid, and CSF tau pathology to prospectively predict cognitive
      and clinical decline in 347 cognitive normal (CN; baseline age range = 59.7-90.1,
      98.85% white) and 599 mild cognitively impaired (MCI; baseline age range = 54.4
      91.4, 98.83% white) individuals from the Alzheimer's Disease Neuroimaging
      Initiative 1, GO, and 2. We further investigated the association of PHS with post
      mortem amyloid load and neurofibrillary tangles in the Religious Orders Study and
      Memory and Aging Project (ROSMAP) cohort (N = 485, age at death range = 71.3
      108.3). In CN and MCI individuals, we found that amyloid and total tau positivity
      systematically varies as a function of PHS. For individuals in greater than the
      50th percentile PHS, the positive predictive value for amyloid approached 100%;
      for individuals in less than the 25th percentile PHS, the negative predictive
      value for total tau approached 85%. High PHS individuals with amyloid and tau
      pathology showed the steepest longitudinal cognitive and clinical decline, even
      among APOE epsilon4 noncarriers. Among the CN subgroup, we similarly found that
      PHS was strongly associated with amyloid positivity and the combination of PHS
      and biomarker status significantly predicted longitudinal clinical progression.
      In the ROSMAP cohort, higher PHS was associated with higher post-mortem amyloid
      load and neurofibrillary tangles, even in APOE epsilon4 noncarriers. Together,
      our results show that even after accounting for APOE epsilon4 effects, PHS may be
      useful in MCI and preclinical AD therapeutic trials to enrich for biomarker
      positive individuals at highest risk for short-term clinical progression.

PMID- 29177682
TI  - Density functional theory study of structural and electronic properties of trans
      and cis structures of thiothixene as a nano-drug.
AB  - The geometrical structure, electronic and optical properties, electronic
      absorption spectra, vibrational frequencies, natural charge distribution, MEP
      analysis and thermodynamic properties of the trans and cis structures of the drug
      thiothixene were investigated using density functional theory (DFT) and time
      dependent DFT (TDDFT) methods with the B3LYP hybrid functional and 6-311 + G(d,p)
      basis set. The results of the calculations demonstrate that the cis structure of
      thiothixene has appropriate quantum properties that can act as an active
      medicine. The relative energies of trans and cis structures of thiothixene shows
      that the cis structure is more stable than the trans structure, with a small
      energy difference. TDDFT calculations show that the cis structure of thiothixene
      has the best absorption properties. The calculated NLO properties show that the
      NLO properties of the cis structure of thiothixene are higher than the trans
      structure, and the fact that the chemical hardness of the cis structure is lower
      than that of the trans structure that indicates that the reactivity and charge
      transfer of the cis isomer of thiothixene is higher than that of trans
      thiothixene. The molecular electrostatic potential (MEP) maps of both structures
      of thiothixene demonstrate that the oxygen atoms of the molecule are appropriate
      areas for electrophilic reactions. The vibrational frequencies of the two
      conformations of thiothixene demonstrate that both structures of thiothixene have
      almost similar modes of vibrations. The calculated thermodynamic parameters show
      that these quantities increase with enhancing temperature due to the enhancement
      of molecular vibrational intensities with temperature. Graphical abstract
      Trans/Cis isomerization of thiothixene drug.

PMID- 29177681
TI  - Clinical strategy of diagnosing and following patients with nonalcoholic fatty
      liver disease based on invasive and noninvasive methods.
AB  - Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic liver
      injury in many countries. The incidence of NAFLD is rising rapidly in both adults
      and children, because of the currently ongoing epidemics of obesity and type 2
      diabetes. Notably, histological liver fibrosis is recognized as the main
      predictive factor for the overall long-term outcome of NAFLD, including
      cardiovascular disease and liver-related mortality. Thus, staging of liver
      fibrosis is essential in determining the prognosis and optimal treatment for
      patients with NAFLD and in guiding surveillance for the development of
      hepatocellular carcinoma (HCC). Whereas liver biopsy remains the gold standard
      for staging liver fibrosis, it is impossible to enforce liver biopsy in all
      patients with NAFLD. Noninvasive biological markers, scoring systems and
      noninvasive modalities are increasingly being developed and investigated to
      evaluate fibrosis stage of NAFLD patients. This review will highlight recent
      studies on the diagnosis and staging of NAFLD based on invasive (liver biopsy) or
      noninvasive (biomarker, scoring systems, US-based elastography and MR
      elastography) methods.

PMID- 29177683
TI  - A temporal and spatial monitoring of organotin pollution in a harborside region
      of Brazil by imposex and ecological quality ratio using Leucozonia nassa.
AB  - This study represents the first use of Leucozonia nassa (Mollusca-Gastropoda) in
      a program of long-term monitoring. Specimens of L. nassa were collected between
      2006 and 2014 and analyzed for the occurrence of imposex in two areas in
      Southeastern Brazil, one control area and another characterized by the presence
      of many ports and marinas. Imposex was evaluated in nine sites based on the
      percentage of females exhibiting imposex (I%), relative penis length index and
      vas deferens sequence index, classical indices to evaluate tributyltin (TBT)
      impacts. Moreover, this study uses for the first time in a tropical environment
      the ecological quality ratio (EQR), an approach to verify the imposex levels as
      an indicator of the impact by organotin compounds according to the EU Water
      Framework Directive. The results confirm the occurrence of high levels of imposex
      in L. nassa with all the indices evaluated. Furthermore, the results also
      indicate that, despite the international ban, antifouling paints based on TBT are
      still possibly used in Brazil. In addition, this study shows that L. nassa has
      the characteristics that make it a suitable bioindicator to monitor TBT
      pollution, and that the use of the EQR may create important data regarding this
      problem.

PMID- 29177684
TI  - The effects of chilling-light stress on photosystems I and II in three
      Paphiopedilum species.
AB  - BACKGROUND: Low temperatures pose a critical limitation to the physiology and
      survival of chilling-sensitive plants. One example is the genus Paphiopedilum
      (Orchidaceae), which is mainly native to tropical and subtropical areas from Asia
      to the Pacific islands. However, little is known about the physiological
      mechanism(s) underlying its sensitivity to chilling temperature. We examined how
      chilling-light stress influences the activities of photosystem I (PSI) and
      photosystem II (PSII) in three species: P. armeniacum, P. micranthum, and P.
      purpuratum. All originate from different distribution zones that cover a range of
      temperatures. RESULTS: Photosystem II of three Paphiopedilum species was
      remarkable sensitivity to chilling stress. After 8 h chilling stress, the maximum
      quantum yield of PSII of three species of Paphiopedilum was significantly
      decreased, especially in P. purpuratum. The quantity of efficient PSI complex (P
      m ) value did not significantly differ after 8 h chilling treatment compared to
      the original value in three species. The stronger PSII photoinhibition and
      significantly less capacity for cyclic electron flow (CEF) were observed in P.
      purpuratum. CONCLUSIONS: In conclusion, the three species of Paphiopedilum showed
      significant PSII photoinhibition when exposed to 4  degrees C chilling treatment.
      However, their PSI activities were not susceptible to chilling-light stress
      during 8 h. The CEF was important for the photoprotection of PSI and PSII in P.
      armeniacum and P. micranthum under chilling conditions. Our findings suggested
      that the photosynthetic characteristics of Paphiopedilum were well adapted to
      their habitat.

PMID- 29177685
TI  - Postural stability deficit could predict ankle sprains: a systematic review.
AB  - PURPOSE: To perform a systematic review aimed to determine (1) if the postural
      stability deficit represents a risk factor for ankle sprains; (2) the most
      effective postural stability evaluation to predict ankle sprains and (3) eventual
      confounding factors that could influence postural stability and ankle sprain
      risk. METHODS: A systematic electronic search was performed in MEDLINE, EMBASE
      and CINAHL using the search terms (balance) OR (postural stability) matched with
      (lower limb) OR (ankle) OR (foot) and (sprain) OR (injury) on October 2 2017. All
      prospective studies that evaluated postural stability as risk factor for ankle
      sprains were included. The PRISMA Checklist guided the reporting and data
      abstraction. Methodological quality of all included papers was carefully
      assessed. RESULTS: Fifteen studies were included, evaluating 2860 individuals.
      Various assessment tools or instruments were used to assess postural stability.
      The injury incidence ranged from 10 to 34%. Postural stability deficit was
      recognized as risk factor for ankle sprain (OR = 1.22-10.2) in 9 cases [3 out of
      3 with Star Excursion Balance Test (SEBT)]. Among the six studies that measured
      the center-of-gravity sway, five were able to detect worse postural stability in
      athletes that sustained an ankle sprain. In nine cases, the measurement of
      postural stability did not show any statistical relationship with ankle sprains
      (four out of five with examiner evaluation). In the studies that excluded
      patients with history of ankle sprain, postural stability was reported to be a
      significant risk factor in five out of six studies. CONCLUSIONS: The ultimate
      role of postural stability as risk factor for ankle sprains was not defined, due
      to the high heterogeneity of results, patient's populations, sports and methods
      of postural stability evaluation. Regarding assessment instruments, measurement
      of center-of-gravity sway could detect athletes at risk, however, standardized
      tools and protocols are needed to confirm this finding. The SEBT could be
      considered a promising tool that needs further investigation in wider samples.
      History of ankle sprains is an important confounding factor, since it was itself
      a source of postural stability impairment and a risk factor for ankle sprains.
      These information could guide clinicians in developing screening programs and
      design further prospective cohort studies comparing different evaluation tools.
      LEVEL OF EVIDENCE: I (systematic review of prospective prognostic studies).

PMID- 29177687
TI  - Epigenetic factors Polycomb (Pc) and Suppressor of zeste (Su(z)2) negatively
      regulate longevity in Drosophila melanogaster.
AB  - The process of aging is a hallmark of the natural life span of all organisms and
      individuals within a population show variability in the measures of age related
      performance. Longevity and the rate of aging are influenced by several factors
      such as genetics, nutrition, stress, and environment. Many studies have focused
      on the genes that impact aging and there is increasing evidence that epigenetic
      factors regulate these genes to control life span. Polycomb (PcG) and trithorax
      (trxG) protein complexes maintain the expression profiles of developmentally
      important genes and regulate many cellular processes. Here, we report that
      mutations of PcG and trxG members affect the process of aging in Drosophila
      melanogaster, with perturbations mostly associated with retardation in aging. We
      find that mutations in polycomb repressive complex (PRC1) components Pc and
      Su(z)2 increase fly survival. Using an inducible UAS-GAL4 system, we show that
      this effect is tissue-specific; knockdown in fat body, but not in muscle or brain
      tissues, enhances life span. We hypothesize that these two proteins influence
      life span via pathways independent of their PRC1 functions, with distinct effects
      on response to oxidative stress. Our observations highlight the role of global
      epigenetic regulators in determining life span.

PMID- 29177686
TI  - Preclinical animal study of the NIPRO-ventricular assist device for use in
      pediatric patients.
AB  - Although the outcomes of patients with end-stage heart failure treated with
      implantable left ventricular assist devices have improved, extracorporeal left
      ventricular assist devices continue to play an important role, especially in
      pediatric patients. The present study aimed to examine the long-term
      biocompatibility of a small-sized extracorporeal pneumatic left ventricular
      assist device (NIPRO-LVAD) used in a 30- to 90-day animal experiment. The NIPRO
      LVAD was designed for pediatric patients or small-sized adults. The left
      ventricular assist device system was installed in four adult Shiba goats weighing
      25.7 +/- 4.78 kg via a left thoracotomy. The outflow graft was sewn to the
      descending aorta and the inflow cannula was placed in the left ventricle through
      the left ventricular apex. Oral antiplatelet (aspirin) and oral anticoagulation
      therapies (warfarin) were also administered. Three out of four animals survived
      for a 30-day period and two goats survived for 90 days. One animal was killed
      early because of low pump flow due to obstruction of the inflow cannula by a left
      ventricular endocardial vegetation. The blood pump exhibited sufficient
      hydrodynamic performance with blood flows of 1.5-2.0 L/min. The animals'
      laboratory values were within normal limits by postoperative day 7. There was no
      significant thrombus formation on the housing, diaphragm, or valves of the
      explanted pumps. Based on the biocompatibility demonstrated in this animal study,
      the explanted small-sized pump may be suitable for use in left ventricular assist
      device systems for pediatric patients.

PMID- 29177688
TI  - Trifurcation of the tibial nerve within the tarsal tunnel.
AB  - The tibial nerve is the larger terminal branch of the sciatic nerve and it
      terminates in the tarsal tunnel by giving lateral and medial plantar nerves. We
      present a rare case of trifurcation of the tibial nerve within the tarsal tunnel.
      The variant nerve curves laterally after branching from the tibial nerve and
      courses deep to quadratus plantae muscle. Interestingly, posterior tibial artery
      was also terminating by giving three branches. These branches were accompanying
      the terminal branches of the tibial nerve.

PMID- 29177689
TI  - Expression of Cyclin D1 protein in residual tumor after neoadjuvant chemotherapy
      for breast cancer.
AB  - PURPOSE: Hormone receptor (HR)-positive breast cancer (BC) shows a poor response
      to neoadjuvant chemotherapy (NACT). New treatment targets like the Cyclin D1
      CDK4/CDK6 complex are promising adjuvant/post-neoadjuvant therapeutic strategies.
      Evaluating Cyclin D1 overexpression in residual tumor could recognize those
      patients that benefit most from such post-neoadjuvant treatment. In this study,
      we determined Cyclin D1 expression in residual BC after NACT. Secondary aims were
      to correlate Cyclin D1 expression levels with clinicopathological parameters and
      to assess its prognostic value after NACT. METHODS: We retrospectively assessed
      the nuclear expression of Cyclin D1 on tissue microarrays with residual tumor
      from 284 patients treated in the neoadjuvant GeparTrio (n = 186) and GeparQuattro
      (n = 98) trials. Evaluation was performed with a standardized immunoreactive
      score (IRS) after selecting a cut-off value. RESULTS: A high expression level
      (IRS >= 6) of Cyclin D1 was found in 37.3% of the assessed specimens. An
      increased Cyclin D1 expression was observed in HR-positive tumors, compared to HR
      negative tumors (p = 0.02). Low Cyclin D1 levels correlated with clinical tumor
      stage 1-3 (p = 0.03). Among patients with HR-positive/Her2-negative tumors and
      high Cyclin D1 expression, a better disease-free survival (DFS) was graphically
      suggested, but not significant (p = 0.21). CONCLUSION: Our study demonstrates a
      measurable nuclear expression of Cyclin D1 in post-neoadjuvant residual tumor
      tissue of HR-positive BC. Cyclin D1 expression was not prognostic for DFS after
      NACT. Our results and defined cut-off suggest that the marker can be used to
      stratify tumors according to protein expression levels. Based on this, a
      prospective evaluation is currently performed in the ongoing Penelope-B trial.

PMID- 29177690
TI  - Obesity and Regional Immigrant Density.
AB  - Canada has an increasingly large immigrant population. Areas of higher immigrant
      density, may relate to immigrants' health through reduced acculturation to
      Western foods, greater access to cultural foods, and/or promotion of salubrious
      values/practices. It is unclear, however, whether an association exists between
      Canada-wide regional immigrant density and obesity among immigrants. Thus, we
      examined whether regional immigrant density was related to obesity, among
      immigrants. Adult immigrant respondents (n = 15,595) to a national population
      level health survey were merged with region-level immigrant density data. Multi
      level logistic regression was used to model the odds of obesity associated with
      increased immigrant density. The prevalence of obesity among the analytic sample
      was 16%. Increasing regional immigrant density was associated with lower odds of
      obesity among minority immigrants and long-term white immigrants. Immigrant
      density at the region-level in Canada may be an important contextual factor to
      consider when examining obesity among immigrants.

PMID- 29177691
TI  - Differential association of GABAB receptors with their effector ion channels in
      Purkinje cells.
AB  - Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and
      postsynaptically through the modulation of different effector signalling
      pathways. Here, we analysed the distribution of GABAB receptors using highly
      sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar
      Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more
      abundantly, on postsynaptic compartments, showing both scattered and clustered
      distribution patterns. Quantitative analysis of immunoparticles revealed a somato
      dendritic gradient, with the density of immunoparticles increasing 26-fold from
      somata to dendritic spines. To understand the spatial relationship of GABAB
      receptors with two key effector ion channels, the G protein-gated inwardly
      rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel,
      biochemical and immunohistochemical approaches were performed. Co
      immunoprecipitation analysis demonstrated that GABAB receptors co-assembled with
      GIRK and CaV2.1 channels in the cerebellum. Using double-labelling immunoelectron
      microscopic techniques, co-clustering between GABAB1 and GIRK2 was detected in
      dendritic spines, whereas they were mainly segregated in the dendritic shafts. In
      contrast, co-clustering of GABAB1 and CaV2.1 was detected in dendritic shafts but
      not spines. Presynaptically, although no significant co-clustering of GABAB1 and
      GIRK2 or CaV2.1 channels was detected, inter-cluster distance for GABAB1 and
      GIRK2 was significantly smaller in the active zone than in the dendritic shafts,
      and that for GABAB1 and CaV2.1 was significantly smaller in the active zone than
      in the dendritic shafts and spines. Thus, GABAB receptors are associated with
      GIRK and CaV2.1 channels in different subcellular compartments. These data
      provide a better framework for understanding the different roles played by GABAB
      receptors and their effector ion channels in the cerebellar network.

PMID- 29177693
TI  - Neuroprotective effects of nootkatone from Alpiniae oxyphyllae Fructus against
      amyloid-beta-induced cognitive impairment.
AB  - The sesquiterpene nootkatone (NKT), isolated from Alpiniae oxyphyllae Fructus,
      was shown to possess protective effects on neurons. In our study, by using an
      Alzheimer's disease (AD) model of mice induced by intracerebroventricular
      (i.c.v.) injection of Abeta1-42 oligomers, we investigated the effects of NKT on
      memory impairment and further evaluated the pathological changes of mice. AD mice
      were treated by i.c.v. injection of NKT (at a dose of 0.02 mg/kg and 0.20 mg/kg)
      or vehicle (PBS) into the lateral ventricle once daily for 5 consecutive days.
      The behavioral tasks were performed, and levels of some biochemical indicators
      and histopathological changes of the brain were evaluated to elucidate the
      mechanism of NKT in the treatment of AD. The results revealed that NKT
      significantly improved the neurobehavioral performance of the AD mice in the Y
      maze and Morris water maze tests. More importantly, NKT treatment decreased the
      malondialdehyde (MDA), Abeta as well as the acetylcholin esterase (AChE) levels
      in the mice brain, while increased the glutathione peroxidase (GSH-Px) levels
      with improved histopathological changes in the hippocampus. These findings
      provided evidences for the beneficial role of NKT in Abeta1-42-induced mice AD
      model linking to anti-oxidative and anti-AChE activities with inhibitory effect
      against Abeta accumulation.

PMID- 29177694
TI  - Phytoremediation of Cadmium by Native Plants Grown on Mining Soil.
AB  - The Gumuskoy mining area is located about 25 km west of Kutahya and is the
      largest silver deposit in Turkey. The present study investigated translocation
      and accumulation of cadmium (Cd) from the soil into 11 native plants. Plant and
      soil samples were collected from the field, and Cd concentrations were analyzed
      by inductively coupled plasma mass spectroscopy. Mean Cd values in the soil,
      root, and shoot of native plants in the study area were 82.8 +/- 5, 55.4 +/- 6,
      and 43.5 +/- 4 mg kg- 1, respectively. Plants were separated into several groups
      according to the enrichment coefficients for shoot and root values of plants.
      These groups showed Carduus nutans and Phlomis could be potentially
      bioaccumulator plants useful for phytoremediation of mining soils contaminated by
      Cd.

PMID- 29177695
TI  - Blood Lead Levels in Captive Giant Pandas.
AB  - Fifteen giant pandas (Ailuropoda melanoleuca) from the Chinese Conservation and
      Research Center for the Giant Panda (CCRCGP) in Bifengxia, Sichuan, China were
      analyzed for blood lead concentrations (Pb-B) during the 2017 breeding season.
      Thirteen of the 15 bears showed Pb-B below the method detection limit (MDL) of
      3.3 ug/dL. The two remaining bears, although above the MDL, contained very low
      concentrations of lead of 3.9 and 4.5 ug/dL. All 15 giant pandas in this analysis
      had Pb-B concentrations that were within normal background concentrations for
      mammals in uncontaminated environments. For a threatened species, whose native
      country is plagued by reports of extremely high air pollution, our findings
      suggest that giant pandas at the CCRCGP are not absorbing lead at concentrations
      that would adversely affect their health.

PMID- 29177692
TI  - Dermatological Complications After Solid Organ Transplantation.
AB  - Organ transplant recipients (OTRs) are a population at high risk for cutaneous
      adverse events. Their early recognition and appropriate treatment is an important
      component of the clinical management of OTRs and should be optimally dealt with
      by dermatologists working in the context of a transplant dermatology clinic. Skin
      examination should be a standard procedure before performing organ
      transplantation to assess conditions which may be difficult to manage after the
      transplant procedure has been performed or which may represent a contraindication
      to transplantation, e.g., malignant melanoma. It also offers an opportunity to
      educate patients on skin care after organ transplantation. Skin infections can
      occur at any time after organ transplantation and include viral, bacterial, and
      fungal opportunistic infections. The risk of reactivation of latent viruses, such
      as varicella-zoster virus (VZV) and cytomegalovirus (CMV), is high. Bacterial
      infections are frequent and may be caused by unusual agents such Actinomyces,
      Mycobacteria, Legionella, or Nocardia. A large spectrum of fungal infections may
      occur, ranging from superficial (e.g., dermatophytes) to deeper and more severe
      ones (Alternaria, Aspergillus, Cryptococcus, Histoplasma). Drug-related
      idiosyncratic reactions usually occur early after the introduction of the
      causative drug, e.g., hypersensitivity reaction to azathioprine. On the long-term
      run, cutaneous effects due to cumulative drug toxicity, e.g., sebaceous
      hyperplasia from cyclosporine, may appear. Rare immunologically driven
      inflammatory reactions may occur in OTRs such as GVH or autoimmune disease.
      Tumors are particularly frequent. Kaposi's sarcoma, associated with persistent
      human herpes virus 8 (HHV8) infection, and cutaneous anaplastic large-cell
      lymphoma (ALCL) occur early after transplantation. Other cancers, such as
      nonmelanoma skin cancer (NMSCs), associated with persistent human papillomavirus
      (HPV) infections, malignant melanoma, Merkel cell carcinoma, or adnexal tumors,
      manifest later with an incidence which is much higher than observed in the
      general population. The incidence increases further after a first NMSC occurs.

PMID- 29177696
TI  - Leaching Characteristics of Calcium and Strontium from Phosphogypsum Under Acid
      Rain.
AB  - Phosphogypsum (PG) stored close to phosphorus chemical plants has caused
      worldwide environmental problems. Column leaching experiments were conducted to
      evaluate Ca and Sr leaching from PG under simulated acid rain at pH levels
      typical for rain in the study region (Shifang, China). High concentrations of Ca
      and Sr in leachates in the first five leaching events could pollute the soil and
      groundwater around the PG. Leachates pH was lower than and had no correlation
      with simulated rain pH. No correlations between simulated rain pH and cumulative
      Ca and Sr content in leachates were noted. Around 2.0%-2.2% of Ca and 0.5%-0.6%
      of Sr were leached out from PG by the simulated summer rainfall in Shifang.
      Electrical conductivity values, Ca and Sr concentrations at bottom sections of PG
      columns were higher than those of top sections, while pH values showed a reverse
      trend. More precautions should be taken to protect the environment around PG
      stacks.

PMID- 29177697
TI  - Neuroprotective and Anti-inflammatory Effects of a Dodecamer Peptide Harboring
      Ninjurin 1 Cell Adhesion Motif in the Postischemic Brain.
AB  - It has been reported that the innate immune response plays important roles in
      brain ischemia and that the infiltration of blood-derived immune cells is a key
      initiator of this response. Nerve injury-induced protein 1 (Ninjurin 1, Ninj1) is
      a cell adhesion molecule responsible for cell-to-cell interactions between immune
      cells and endothelial cells. In the present study, we investigated the
      proinflammatory and neuroprotective effects of Ninj1 and a dodecamer peptide
      harboring Ninj1 N-terminal adhesion motif (N-NAM, Pro26~Asn37) in a rat middle
      cerebral artery occlusion (MCAO) model of stroke. Ninj1 was predominantly induced
      in neutrophils and endothelial cells in the ischemic hemispheres around 12 h to 1
      day post-MCAO, which coincided with a massive neutrophil influx. We demonstrated
      that intranasal administration of Ninj1 small interfering RNA (siRNA) or N-NAM
      significantly blocked neutrophil infiltration in postischemic brains. In
      addition, intranasal administration of Ninj1 siRNA or N-NAM reduced the mean
      infarct volume to 46.5 +/- 9.2 or 30.6 +/- 11.7% of that of the PBS-treated MCAO
      controls, respectively, which was accompanied by significant amelioration of
      neurological and motor deficits. We showed that N-NAM or Ninj1 siRNA effectively
      blocked the adhesion and transendothelial migration of TNF-alpha-stimulated human
      myelocytic leukemia cells to human umbilical vein endothelial cells and similarly
      suppressed adhesion and migration of monocytes. Activations of phosphoinositide 3
      kinase and Ras-related C3 botulinum toxin substrate 1 are involved in these Ninj1
      mediated processes and can be inhibited by N-NAM or Ninj1 siRNA. These results
      indicate that Ninj1 plays an important role in neutrophil infiltration in the
      postischemic brain and N-NAM confers robust neuroprotective and anti-inflammatory
      effects by inhibiting Ninj1-mediated infiltration of neutrophils.

PMID- 29177698
TI  - Evolution of early phase clinical trials in oncology.
AB  - The therapeutic armamentarium for the treatment of cancer has rapidly evolved
      with the advent of molecularly targeted and immuno-oncology agents. Dramatic and
      prolonged responses observed in patients with advanced cancers have created
      excitement and promise for expedited development of effective new treatments.
      However, this has also necessitated a rethinking of our early phase clinical
      trial designs and the process of optimally developing a novel agent. In this
      review, we discuss the current state and future directions of phase I clinical
      trials in oncology. Firstly, we cover the statistical methodologies behind rules
      and model-based dose escalation designs, and what the future holds for optimal
      dose selection beyond targeting the maximum tolerated dose. Next, we discuss the
      recent adoption of seamless expansion strategies to expedite drug development
      timelines, highlighted by the pembrolizumab KEYNOTE-001 trial, and potential
      pitfalls with this approach. Finally, we delve into the concepts behind genomic
      matching trials, including early success stories and the challenges that lie
      ahead.

PMID- 29177699
TI  - A Phase IC Study Evaluating the Safety, Tolerability, Pharmacokinetics, and
      Cognitive Outcomes of BI 409306 in Patients with Mild-to-Moderate Schizophrenia.
AB  - INTRODUCTION: This randomized, double-blind, parallel-group study investigated
      the safety, tolerability, pharmacokinetics (PK), and cognitive outcomes of BI
      409306-a selective phosphodiesterase 9A (PDE9A) inhibitor-in patients with
      schizophrenia. METHODS: Patients with mild-to-moderate schizophrenia were
      randomized (1:1:1:1) to receive BI 409306 at 25, 50, or 100 mg or placebo once
      daily over 14 days. The primary endpoints were safety and tolerability; the
      secondary endpoints were PK and cognitive outcomes. RESULTS: Of the 40 randomized
      patients, 38 (95%) completed the study. Patients were predominantly male (87.5%;
      mean age, 40.2 years). After a single dose, C max was reached within 30-45 min.
      The geometric mean (gMean) C max and AUC0-infinity ranged from 138 to 998 nmol/L
      and 217 to 2020 nmol?h/L, respectively. Elimination was rapid (gMean t 1/2 range
      1.10-1.85 h). After multiple doses, C max,ss was reached within 1 h; elimination
      was similar to that observed after a single dose. Total exposure at steady state
      and after a single dose were similar (accumulation ratio range: AUC, 0.758-1.13
      and Cmax, 0.768-1.40). No deaths, adverse events (AEs) leading to
      discontinuation, or serious AEs were observed. Treatment-emergent AEs were mild,
      with no apparent dose-related trends. There was no worsening of schizophrenia
      symptoms (Positive and Negative Syndrome Scale) and no trends in suicidality
      (Columbia Suicide Severity Rating Scale). The Hopkins Verbal Learning Test
      Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) showed no
      effect on cognitive function. CONCLUSION: Administration of BI 409306 in patients
      with mild-to-moderate schizophrenia resulted in satisfactory safety and
      tolerability. BI 409306, PK was characterized by rapid absorption, monophasic to
      biphasic elimination, and minor accumulation with multiple dosing. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT01892384. FUNDING: Boehringer
      Ingelheim Pharma GmbH & Co. KG.

PMID- 29177700
TI  - Novel Mutations in PLOD2 Cause Rare Bruck Syndrome.
AB  - Bruck syndrome is a rare autosomal recessive form of osteogenesis imperfecta
      (OI), which is mainly characterized by joint contractures and recurrent fragility
      fractures. Mutations in FKBP10 and PLOD2 were identified as the underlying
      genetic defects of Bruck syndrome. Here we investigated the phenotypes and the
      pathogenic mutations of three unrelated Chinese patients with Bruck syndrome.
      Clinical fractures, bone mineral density (BMD), bone turnover biomarkers, and
      skeletal images were evaluated in detail. The pathogenic mutations were
      identified by targeted next-generation sequencing and subsequently confirmed by
      Sanger sequencing and cosegregation analysis. We also evaluated the effects of
      zoledronic acid on bone fracture incidence and BMD of the patients. Three
      patients had congenital joint contractures, recurrent fragility fractures,
      camptodactyly, clubfoot, scoliosis, but without dentinogenesis imperfecta and
      hearing loss. Five novel heterozygous mutations were detected in PLOD2, including
      three heterozygous missense mutations (c.1138C>T, p.Arg380Cys; c.1153T>C,
      p.Cys385Arg; and c.1982G>A, p.Gly661Asp), one heterozygous nonsense mutation
      (c.2038C>T, p.Arg680X), and one heterozygous splice-site mutation (c.503-2A>G).
      Their parents were all heterozygous carriers of these mutations in PLOD2. No
      clear genotype-phenotype correlations were found in these patients with PLOD2
      mutations. Z-score of BMD was significantly increased, but scoliosis progressed
      and new bone fractures occurred during the treatment of zoledronic acid. Our
      findings expanded the spectrum of gene mutations of Bruck syndrome.

PMID- 29177702
TI  - [Bruch's membrane opening minimum rim width : Correlation and diagnostic accuracy
      in comparison to peripapillary retinal nerve fiber layer thickness].
AB  - BACKGROUND: Glaucoma is one of the main causes of blindness in the Western
      hemisphere. Because the disease often painlessly progresses it remains unnoticed
      until major optic nerve head damage occurs in many cases. That is why new, more
      sensitive diagnostic methods are needed. Bruch's membrane opening minimum rim
      width (BMO-MRW), measured with the new glaucoma module premium edition (GMPE) was
      recently introduced as a more accurate tool to detect glaucomatous changes. The
      purpose of this study was to assess the correlation of SPECTRALIS(r) spectral
      domain optical coherence tomography (SD-OCT) and the GMPE anatomic positioning
      module (APS module) for retinal nerve fiber layer thickness (RNFLT) measurements.
      The second aim was to assess the diagnostic accuracy of BMO-MRW. METHODS:
      Prospective study of 41 eyes (41 patients) with glaucoma and 26 eyes from 26
      healthy controls. Scans were obtained using SPECTRALIS(r) SD-OCT and RNFLT was
      measured with both modules and compared using Spearman's rank test. The BMO-MRW
      was assessed by GMPE. Sensitivity, specificity and area under receiver operating
      characteristics curves (AUROC) of each sector of the optic nerve were calculated
      and compared using the method of Delong et al. RESULTS: We found a positive
      correlation (0.694-0.955, p < 0.0001) between RNFLT measurements by standard SD
      OCT and all diameters of RNFLT of APS module within all sectors. The AUROC of
      RNFLT in standard SD-OCT was 0.693 for the inferior nasal sector (NI) and BMO-MRW
      was 0.85 in NI. The difference in AUROC was statistically significant (p =
      0.0049). No other sector showed statistically significant differences.
      CONCLUSION: The RNFLT measurements of both modules showed a positive correlation
      and appear to be comparable. The BMO-MRW in one sector (NI) showed a
      significantly higher accuracy of measurement than standard RNFLT. All other
      sectors showed a comparable accuracy of measurement.

PMID- 29177701
TI  - Ultrasound classification of traumatic distal biceps brachii tendon injuries.
AB  - OBJECTIVE: The present work is aimed at analysing ultrasound findings in patients
      with distal biceps brachii tendon (DBBT) injuries to assess the sensitivity of
      ultrasound in detecting the different forms of injury, and to compare ultrasound
      results with magnetic resonance imaging (MRI) and surgical results. MATERIALS AND
      METHODS: A total of 120 patients with traumatic DBBT injuries examined between
      2011 and 2015 were analysed. We compared ultrasound results with MRI results when
      surgery was not indicated and with MRI and surgical results when surgery was
      indicated. RESULTS: For major DBBT injuries (complete tears and high-grade
      partial tears), the concordance study between exploration methods and surgical
      results found that ultrasound presented a slight statistically significant
      advantage over MRI (ultrasound: kappa = 0.95-very good-95% CI 0.88 to 1.01, MRI:
      kappa = 0.63-good-95% CI 0.42 to 0.84, kappa difference p < 0.01). Minor
      injuries, in which most tendon fibres remain intact (tendinopathies, elongations
      and low-grade partial tears), are the most difficult to interpret, as ultrasound
      and MRI reports disagreed in 12 out of 39 cases and no surgical confirmation
      could be obtained. CONCLUSIONS: Based on present results and previous MRI
      classifications, we establish a traumatic DBBT injury ultrasound classification.
      The sensitivity and ultrasound-surgery correlation results in the diagnosis of
      major DBBT injuries obtained in the present study support the recommendation that
      ultrasound can be used as a first-line imaging modality to evaluate DBBT
      injuries.

PMID- 29177703
TI  - Evaluation of four commercial quantitative real-time PCR kits with inhibited and
      degraded samples.
AB  - DNA quantification is a vital step in forensic DNA analysis to determine the
      optimal input amount for DNA typing. A quantitative real-time polymerase chain
      reaction (qPCR) assay that can predict DNA degradation or inhibitors present in
      the sample prior to DNA amplification could aid forensic laboratories in creating
      a more streamlined and efficient workflow. This study compares the results from
      four commercial qPCR kits: (1) Investigator(r) Quantiplex(r) Pro Kit, (2)
      Quantifiler(r) Trio DNA Quantification Kit, (3) PowerQuant(r) System, and (4)
      InnoQuant(r) HY with high molecular weight DNA, low template samples, degraded
      samples, and DNA spiked with various inhibitors.The results of this study
      indicate that all kits were comparable in accurately predicting quantities of
      high quality DNA down to the sub-picogram level. However, the InnoQuant(R) HY kit
      showed the highest precision across the DNA concentration range tested in this
      study. In addition, all kits performed similarly with low concentrations of
      forensically relevant PCR inhibitors. However, in general, the Investigator(r)
      Quantiplex(r) Pro Kit was the most tolerant kit to inhibitors and provided the
      most accurate quantification results with higher concentrations of inhibitors
      (except with salt). PowerQuant(r) and InnoQuant(r) HY were the most sensitive to
      inhibitors, but they did indicate significant levels of PCR inhibition. When
      quantifying degraded samples, each kit provided different degradation indices
      (DI), with Investigator(r) Quantiplex(r) Pro indicating the largest DI and
      Quantifiler(r) Trio indicating the smallest DI. When the qPCR kits were paired
      with their respective STR kit to genotype highly degraded samples, the
      Investigator(r) 24plex QS and GlobalFiler(r) kits generated more complete
      profiles when the small target concentrations were used for calculating input
      amount.

PMID- 29177704
TI  - Inconsistent genotyping call at DYS389 locus and implications for interpretation.
AB  - The male-specific Y chromosome short tandem repeat (STR) locus is used widely in
      forensic case, which are useful molecular tool to providing the biological
      evidence for male/female mixture and paternal lineage cases. The Y-STR analysis
      has been greatly facilitated by advent of commercial multiplex kit. However, even
      with well-designed robust multiplex kit, abnormal genotyping profile may be
      observed when encountering with mutations, such as deletion/duplication within
      the target region or mutation at the primer binding site. In this study, a single
      allele shift by five nucleotides for the DYS389I marker between the AmpFlSTR(r)
      Yfiler(r) and Yfiler(r) Plus PCR amplification kits while the same allele count
      for DYS389II was observed in eight unrelated Chinese male individuals. After
      further investigations by re-amplified with three additional multiplex kits,
      sanger, and next-generation sequencing, the discordance was finally proven caused
      by existing rare mutation in those sample, which contained two adjacent SNPs only
      one base apart in the sequence. This paper describes the molecular basis of the
      discordance at DYS389I genotyping between different commercial multiplex kits and
      could provide available information for enhancing of interpretation of abnormal Y
      STR genotyping in forensic practice.

PMID- 29177705
TI  - Acid-facilitated product release from a Mo(IV) center: relevance to oxygen atom
      transfer reactivity of molybdenum oxotransferases.
AB  - We report that pyridinium ions (HPyr+) accelerate the conversion of
      [Tp*MoIVOCl(OPMe3)] (1) to [Tp*MoIVOCl(NCCH3)] (2) by 103-fold, affording 2 in
      near-quantitative yield; Tp* = hydrotris(3,5-dimethyl-1-pyrazolyl)borate. This
      novel reactivity and the mechanism of this reaction were investigated in detail.
      The formation of 2 followed pseudo-first-order kinetics, with the observed pseudo
      first-order rate constant (k obs) linearly correlated with [HPyr+]. An Eyring
      plot revealed that this HPyr+-facilitated reaction has a small positive value of
      ?S ? indicative of a dissociative interchange (Id) mechanism, different from the
      slower associative interchange (Ia) mechanism in the absence of HPyr+ marked with
      a negative ?S ?. Interestingly, log(k obs) was found to be linearly correlated to
      the acidity of substituted pyridinium ions. This novel reactivity is further
      investigated using combined DFT and ab initio coupled cluster methods. Different
      reaction pathways, including Id, Ia, and possible alternative routes in the
      absence or presence of HPyr+, were considered, and enthalpy and free energies
      were calculated for each pathway. Our computational results further underscored
      that the Id route is energetically favored in the presence of HPyr+, in contrast
      with the preferred Ia-NNO pathway in the absence of HPyr+. Our computational
      results also revealed molecular-level details for the HPyr+-facilitated Id route.
      Specifically, HPyr+ initially becomes hydrogen-bonded to the oxygen atom of the
      Mo(IV)-OPMe3 moiety, which lowers the activation barrier for the Mo-OPMe3 bond
      cleavage in a rate-limiting step to dissociate the OPMe3 product. The
      implications of our results were discussed in the context of molybdoenzymes,
      particularly the reductive half-reaction of sulfite oxidase.

PMID- 29177706
TI  - Prognostic value of vasodilator response using rubidium-82 positron emission
      tomography myocardial perfusion imaging in patients with coronary artery disease.
AB  - BACKGROUND: Prognostic value of positron emission tomography (PET) myocardial
      perfusion imaging (MPI) is well established. There is paucity of data on how the
      prognostic value of PET relates to the hemodynamic response to vasodilator
      stress. We hypothesize that inadequate hemodynamic response will affect the
      prognostic value of PET MPI. METHODS AND RESULTS: Using a multicenter rubidium
      (Rb)-82 PET registry, 3406 patients who underwent a clinically indicated
      rest/stress PET MPI with a vasodilator agent were analyzed. Patients were
      categorized as, "responders" [increase in heart rate >= 10 beats per minute (bpm)
      and decrease in systolic blood pressure (SBP) >=10 mmHg], "partial responders"
      (either a change in HR or SBP), and "non-responders" (no change in HR or SBP).
      Primary outcome was all-cause death (ACD), and secondary outcome was cardiac
      death (CD). Ischemic burden was measured using summed stress score (SSS) and %
      left ventricular (LV) ischemia. After a median follow-up of 1.68 years
      (interquartile range = 1.17- 2.55), there were 7.9% (n = 270) ACD and 2.6% (n =
      54) CD. Responders with a normal PET MPI had an annualized event rate (AER) of
      1.22% (SSS of 0-3) and 1.58% (% LV ischemia = 0). Partial and non-responders had
      higher AER with worsening levels of ischemic burden. In the presence of severe
      SSS >=12 and LV ischemia of >=10%, partial responders had an AER of 10.79% and
      10.36%, compared to non-responders with an AER of 19.4% and 12.43%, respectively.
      Patient classification was improved when SSS was added to a model containing
      clinical variables (NRI: 42%, p < 0.001) and responder category was added (NRI:
      61%, p < 0.001). The model including clinical variables, SSS and hemodynamic
      response has good discrimination ability (Harrell C statistics: 0.77 [0.74
      0.80]). CONCLUSION: Hemodynamic response during a vasodilator Rb-82 PET MPI is
      predictive of ACD. Partial and non-responders may require additional risk
      stratification leading to altered patient management.

PMID- 29177707
TI  - A first-in-man PET study of [18F]PSS232, a fluorinated ABP688 derivative for
      imaging metabotropic glutamate receptor subtype 5.
AB  - PURPOSE: Non-invasive imaging of metabotropic glutamate receptor 5 (mGlu5) in the
      brain using PET is of interest in e.g., anxiety, depression, and Parkinson's
      disease. Widespread application of the most widely used mGlu5 tracer,
      [11C]ABP688, is limited by the short physical half-life of carbon-11. [18F]PSS232
      is a fluorinated analog with promising preclinical properties and high
      selectivity and specificity for mGlu5. In this first-in-man study, we evaluated
      the brain uptake pattern and kinetics of [18F]PSS232 in healthy volunteers.
      METHODS: [18F]PSS232 PET was performed with ten healthy male volunteers aged 20
      40 years. Seven of the subjects received a bolus injection and the remainder a
      bolus/infusion protocol. Cerebral blood flow was determined in seven subjects
      using [15O]water PET. Arterial blood activity was measured using an online blood
      counter. Tracer kinetics were evaluated by compartment modeling and parametric
      maps were generated for both tracers. RESULTS: At 90 min post-injection, 59.2 +/-
      11.1% of total radioactivity in plasma corresponded to intact tracer. The
      regional first pass extraction fraction of [18F]PSS232 ranged from 0.41 +/- 0.06
      to 0.55 +/- 0.03 and brain distribution pattern matched that of [11C]ABP688.
      Uptake kinetics followed a simple two-tissue compartment model. The volume of
      distribution of total tracer (V T, ml/cm3) ranged from 1.18 +/- 0.20 for white
      matter to 2.91 +/- 0.51 for putamen. The respective mean distribution volume
      ratios (DVR) with cerebellum as the reference tissue were 0.88 +/- 0.06 and 2.12
      +/- 0.10, respectively. The tissue/cerebellum ratios of a bolus/infusion protocol
      (30/70 dose ratio) were close to the DVR values. CONCLUSIONS: Brain uptake of
      [18F]PSS232 matched the distribution of mGlu5 and followed a two-tissue
      compartment model. The well-defined kinetics and the possibility to use reference
      tissue models, obviating the need for arterial blood sampling, make [18F]PSS232 a
      promising fluorine-18 labeled radioligand for measuring mGlu5 density in humans.

PMID- 29177709
TI  - [Bone defects in endoprosthetic treatment of the shoulder and elbow].

PMID- 29177708
TI  - An Efficient and Effective Design of InP Nanowires for Maximal Solar Energy
      Harvesting.
AB  - Solar cells based on subwavelength-dimensions semiconductor nanowire (NW) arrays
      promise a comparable or better performance than their planar counterparts by
      taking the advantages of strong light coupling and light trapping. In this paper,
      we present an accurate and time-saving analytical design for optimal geometrical
      parameters of vertically aligned InP NWs for maximal solar energy absorption.
      Short-circuit current densities are calculated for each NW array with different
      geometrical dimensions under solar illumination. Optimal geometrical dimensions
      are quantitatively presented for single, double, and multiple diameters of the NW
      arrays arranged both squarely and hexagonal achieving the maximal short-circuit
      current density of 33.13 mA/cm2. At the same time, intensive finite-difference
      time-domain numerical simulations are performed to investigate the same NW arrays
      for the highest light absorption. Compared with time-consuming simulations and
      experimental results, the predicted maximal short-circuit current densities have
      tolerances of below 2.2% for all cases. These results unambiguously demonstrate
      that this analytical method provides a fast and accurate route to guide high
      performance InP NW-based solar cell design.

PMID- 29177710
TI  - Reflections on Recent Research Into Animal-Assisted Interventions in the Military
      and Beyond.
AB  - PURPOSE OF REVIEW: The purpose of the present review was threefold: to address
      the current state of Animal-Assisted Interactions (AAI) within the military; to
      summarize recent literature (within the past three years) in the field of AAI;
      and to discuss trends in AAI research since 2014. RECENT FINDINGS: With regard to
      AAI within the military, several canine interaction programs have been utilized
      to assist service members in coping with various issues. Therapy dogs have been
      deployed with Combat-Operational Stress Control units; they have been integrated
      into medical clinics and behavioral health treatment programs in garrison; and
      policy has been developed to address the use of therapy animals in military
      treatment facilities. General research in AAI has demonstrated efficacy for
      certain presenting issues (stress management, trauma, autism spectrum disorder)
      and specific populations (children, the elderly, acute care patients). Overall
      trends in research include calls for increased consideration for animal welfare
      in AAI and increased rigor in research methodology. Current research supports the
      structured use of therapy dogs in the treatment of various disorders and with
      specific populations, including military service members and veterans; however,
      the need for additional research with rigorous methodology remains.

PMID- 29177711
TI  - What makes the difference in people's lives when they have a mental disorder?
AB  - OBJECTIVES: The objective of this study was to identify which environmental
      factors are the most responsible for the disability experienced by persons with
      mental disorders and whether they differ (1) from those in cardiovascular
      diseases, chronic respiratory conditions, diabetes, and cancer, and (2) depending
      on the capacity level-a proxy for the impact of health conditions on the health
      state of individuals. METHODS: Nationally representative data from 12,265 adults
      in Chile collected in 2015 with the WHO Model Disability Survey was analyzed.
      RESULTS: The availability of personal assistance, frequency of receiving personal
      assistance, and assistive devices for mobility were the most important
      environmental factors across mental and other non-communicable diseases.
      Perception of discrimination and use of health services were also prominent
      factors. There was a huge overlap between the factors found relevant for mental
      and other non-communicable diseases, but a substantial variability depending on
      the intensity of difficulties in capacity. CONCLUSIONS: This study challenges the
      appropriateness of disease-specific approaches and suggests that considering
      intrinsic capacity levels is more informative than focusing on diagnosis alone
      when comparing needs and barriers that affect the performance in daily life of
      specific groups of individuals.

PMID- 29177713
TI  - A Model of Isotope Separation in Plants.
AB  - A model representing isotope separation during water evaporation in plants was
      constructed. The model accounts for substance diffusion, convective transfer and
      evaporation from the surface of the leaves. The dependence of the system's
      separation and enrichment coefficients on various parameters (liquid velocity,
      diffusion coefficient, and potential barriers for molecules and their thermal
      velocities) was determined. A comparison was made between the enrichment
      coefficients calculated from experimental data from different plants and those
      based on the model. Qualitative agreement between the experimental and
      theoretical values was obtained for the case of [Formula: see text], where u is
      the average velocity of water in the plant, h is the height of the plant, and D
      is the diffusion coefficient of the substance.

PMID- 29177712
TI  - Laser photocoagulation as treatment of non-exudative age-related macular
      degeneration: state-of-the-art and future perspectives.
AB  - PURPOSE: To give an updated review of laser approaches to non-exudative age
      related macular degeneration (AMD). METHODS: PubMed and Medline database searches
      were carried out using the terms "laser" and "photocoagulation" associated with
      "age-related macular degeneration", and latest publications up to May 2017 have
      been reviewed. Moreover, the design of an ongoing single-center, non-randomized,
      phase I-II, pilot study, the PASCAL-GA trial, coordinated by F. Bandello, MD and
      G. Querques, MD from the IRCCS Ospedale San Raffaele, is described. RESULTS:
      Either standard or subthreshold laser strategies have been tried to induce
      regression of distinct phenotypes of AMD, as reticular pseudodrusen (RPD),
      nascent geographic atrophy (nGA), and drusen-associated geographic atrophy
      (DAGA), with heterogeneous results. The aim of the PASCAL-GA protocol is to
      assess if subthreshold laser can restore the retinal pigment epithelium function
      in eyes with RPD and nGA offering a protective effect against extensive GA.
      CONCLUSIONS: New-generation medical and surgical approaches, including
      subthreshold laser photocoagulation, may have some success in downstaging AMD.

PMID- 29177714
TI  - Non-invasive high-intensity focused ultrasound for UV-induced hyperpigmentation
      in Fitzpatrick skin types III and IV: a prospective, randomized, controlled,
      evaluator-blinded trial.
AB  - Skin hyperpigmentation is a frequently encountered problem, particularly in
      darker skin types. Unfortunately, standard treatments for this condition have
      shown disappointing results. High-intensity focused ultrasound (HIFU) is commonly
      indicated for skin laxity, but recently was used to treat UV-induced
      hyperpigmentation in animal models. This study is aimed to evaluate the efficacy
      and safety of high-intensity focused ultrasound for UVB-induced hyperpigmentation
      in human subjects. A randomized, evaluator-blinded pilot study was conducted on
      20 subjects. Each subject was induced three hyperpigmentary spots by local
      broadband UVB. After 2 weeks, each spot was randomly allocated to control, low
      energy, and high-energy HIFU. Subjects were instructed to follow up weekly for a
      duration of 1 month. Lightness index measurements, mean improvement scores,
      subjects' satisfaction, pain scores, and side effects were evaluated. All 20
      subjects completed the study. Fourteen subjects had Fitzpatrick (FPT) skin type
      III and six subjects had FPT skin type IV. Twelve subjects showed greater
      improvement at control sites while eight subjects showed greater improvement at
      HIFU-treated sites. In FPT skin type III, HIFU appeared to be inferior to control
      in both lightness index and mean improvement scores, but in FPT skin type IV,
      HIFU had greater lightness index improvement and higher improvement scores than
      control. Side effects were more frequent in high-energy-treated areas. Focused
      ultrasound may be offered in some patients with hyperpigmentary conditions. More
      research is needed to determine proper energy settings for optimal outcome.

PMID- 29177715
TI  - Is bone morphogenic protein-2 useful in revision total hip arthroplasty with
      acetabular defects?

PMID- 29177716
TI  - Pcal_0632, a phosphorylating glyceraldehyde-3-phosphate dehydrogenase from
      Pyrobaculum calidifontis.
AB  - Genome sequence of the hyperthermophilic archaeon Pyrobaculum calidifontis
      contains an open reading frame, Pcal_0632, annotated as glyceraldehyde-3
      phosphate dehydrogenase, which is partially overlapped with phosphoglycerate
      kinase. In the phylogenetic tree, Pcal_0632 clustered with phosphorylating
      glyceraldehyde-3-phosphate dehydrogenases characterized from hyperthermophilic
      archaea and exhibited highest identity of 54% with glyceraldehyde-3-phosphate
      dehydrogenase from Sulfolobus tokodaii. To examine biochemical function of the
      protein, Pcal_0632 gene was expressed in Escherichia coli and the gene product
      was purified. The recombinant enzyme catalyzed the conversion of glyceraldehyde 3
      phosphate and inorganic phosphate into 1,3-bisphosphoglycerate utilizing both NAD
      and NADP as cofactor with a marked preference for NADP. The enzyme was highly
      stable against temperature and denaturants. Half-life of the enzyme was 60 min at
      100  degrees C. It retained more than 60% of its activity even after an
      incubation of 72 h at room temperature in the presence of 6 M urea. High
      thermostability and resistance against denaturants make Pcal_0632 a novel
      glyceraldehyde-3-phosphate dehydrogenase.

PMID- 29177717
TI  - Biochemical characterization of a thermostable endomannanase/endoglucanase from
      Dictyoglomus turgidum.
AB  - Dictyoglomus turgidum is a hyperthermophilic, anaerobic, gram-negative bacterium
      that shows an array of putative glycoside hydrolases (GHs) encoded by its genome,
      a feature that makes this microorganism very interesting for biotechnological
      applications. The aim of this work is the characterization of a hyperthermophilic
      GH5, Dtur_0671, of D. turgidum, annotated as endoglucanase and herein named
      DturCelB in agreement to DturCelA, which was previously characterized. The
      synthetic gene was expressed in Escherichia coli. The purified recombinant enzyme
      is active as a monomer (40 kDa) and CD structural studies showed a conserved
      alpha/beta structure at different temperatures (25 and 70  degrees C) and high
      thermoresistance (Tm of 88  degrees C). Interestingly, the enzyme showed high
      endo-beta-1,4-mannanase activity vs various mannans, but low endo-beta-1,4
      glucanase activity towards carboxymethylcellulose. The K M and V max of DturCelB
      were determined for both glucomannan and CMC: they were 4.70 mg/ml and 473.1
      MUmol/min mg and 1.83 mg/ml and 1.349 MUmol/min mg, respectively. Its optimal
      activity towards temperature and pH resulted to be 70  degrees C and pH 5.4,
      respectively. Further characterization highlighted good thermal stability (~ 50%
      of enzymatic activity after 2 h at 70  degrees C) and pH stability over a broad
      range (> 90% of activity after 1 h in buffer, ranging pH 5-9); resistance to
      chemicals was also observed.

PMID- 29177718
TI  - Unprecedented homotopy perturbation method for solving nonlinear equations in the
      enzymatic reaction of glucose in a spherical matrix.
AB  - The theory of glucose-responsive composite membranes for the planar diffusion and
      reaction process is extended to a microsphere membrane. The theoretical model of
      glucose oxidation and hydrogen peroxide production in the chitosan-aliginate
      microsphere has been discussed in this manuscript for the first time. We have
      successfully reported an analytical derived methodology utilizing homotopy
      perturbation to perform the numerical simulation. The influence and sensitive
      analysis of various parameters on the concentrations of gluconic acid and
      hydrogen peroxide are also discussed. The theoretical results enable to predict
      and optimize the performance of enzyme kinetics.

PMID- 29177719
TI  - Structural features influential to enzymatic hydrolysis of cellulose-solvent
      based pretreated pinewood and elmwood for ethanol production.
AB  - Dissolution of lignocelluloses in N-methylmorpholine-N-oxide (NMMO or NMO) at
      moderate conditions, e.g., 120  degrees C for 3 h under atmospheric pressure, and
      regeneration with water, is among the most effective nonderivatization
      pretreatment for the improvement of enzymatic hydrolysis and ethanol production.
      The effects of the pretreatment on two different types of wood, hardwood elm and
      softwood pine, were compared via physicochemical structural analyses, i.e., FTIR,
      XRD, SEM, TGA, and enzyme adsorption techniques, to relate their properties to
      the extent of enzymatic conversion. After the pretreatment, cellulose was highly
      recovered and characterized to be mainly cellulose II and amorphous cellulose,
      with lower cellulose crystallinity index, higher thermal stability, and more
      favorable surface features for hydrolysis, compared to native woods. Moreover,
      the strength of enzyme binding onto the lignocelluloses, which was directly
      related to the enzymatic hydrolysis rate, increased by 57% and 164% for pinewood
      and elmwood, respectively. The highest total reducing sugars yield for untreated
      pinewood was 9.8% (74 mg/g-substrate) and improved to 58.5% (330 mg/g-substrate)
      after the pretreatment, whereas the corresponding values for elmwood were 14.7%
      (104 mg/g-substrate) vs. 51.4% (274 mg/g-substrate). Furthermore, maximum ethanol
      theoretical yields of 63.5 and 41.4% were obtained from pinewood and elmwood by
      Saccharomyces cerevisiae and Mucor indicus, respectively.

PMID- 29177720
TI  - Recombinant biosynthesis of bacterial cellulose in genetically modified
      Escherichia coli.
AB  - Bacterial cellulose (BC) exhibits unique properties such as high purity compared
      to plant-based cellulose; however, commercial production of BC has remained a
      challenge, primarily due to the strain properties of cellulose-producing
      bacteria. Herein, we developed a functional and stable BC production system in
      genetically modified (GM) Escherichia coli by recombinant expression of both the
      BC synthase operon (bcsABCD) and the upstream operon (cmcax, ccp Ax). BC
      production was achieved in GM HMS174 (DE3) and in GM C41 (DE3) by optimization of
      the culture temperature (22  degrees C, 30  degrees C, and 37  degrees C) and
      IPTG concentration. BC biosynthesis was detected much earlier in GM C41 (DE3)
      cultures (3 h after IPTG induction) than those of Gluconacetobacter hansenii. GM
      HMS174 (DE3) produced dense fibres having a length of approximately 1000-3000 MUm
      and a diameter of 10-20 MUm, which were remarkably larger than the fibres of BC
      typically produced by G. hansenii.

PMID- 29177721
TI  - Is the Positive Bias an ADHD Phenomenon? Reexamining the Positive Bias and its
      Correlates in a Heterogeneous Sample of Children.
AB  - The goals of this study were to (a) evaluate the presence of the positive bias
      (PB) in elementary-school-aged children with and without ADHD when PB is defined
      at the individual level through latent profile analysis and (b) examine the
      extent to which several correlates (i.e., social functioning, aggression,
      depression, and anxiety) are associated with the PB. Participants were 233 youth
      (30% female; 8 to 10 years of age), 51% of whom met criteria for ADHD. During an
      individual evaluation, children and parents completed a battery of questionnaires
      to assess child competence, depression, anxiety, and aggression. Children also
      participated in a novel group session with same-sex unfamiliar peers (half of the
      group was comprised of children with ADHD) to engage in group problem-solving
      tasks and free play activities. After the group session, peers and staff
      completed ratings of each child's behavior (e.g., likeability, rule following).
      The best fitting LPA model for parent and self-ratings of competence revealed
      four profiles: High Competence/Self-Aware; Variable Competence/Self-Aware; Low
      Competence/Self-Aware; and Low Competence/PB, in which the PB was present across
      domains. Only 10% of youth showed a PB and youth with ADHD were no more likely to
      display the PB than their non-ADHD peers with similar levels of low competence.
      Lastly, the Low Competence/Self-Aware profile demonstrated higher levels of
      anxiety and depression than the Low Competence/PB profile; the profiles did not
      differ on aggression or peer or staff ratings of social/behavioral functioning.
      Implications for understanding the PB in children with and without ADHD are
      discussed.

PMID- 29177722
TI  - A cross-sectional study on the mechanical properties of the Achilles tendon with
      growth.
AB  - PURPOSE: This study aimed to elucidate growth pattern of mechanical properties of
      the Achilles tendon and to examine if imbalance between growth of bone and muscle
      tendon unit occurs during adolescence. METHODS: Fourteen elementary school boys,
      30 junior high school boys, 20 high school boys and 15 male adults participated
      in this study. Based on estimated age at peak height velocity (PHV), junior high
      school boys were separated into two groups (before or after PHV). An
      ultrasonography technique was used to determine the length, cross-sectional area,
      stiffness and Young's modulus of Achilles tendon. In addition, the maximum strain
      in "toe region" (strainTP) was determined to describe the balance between growth
      of bone and muscle-tendon unit. RESULTS: No group difference was observed in
      length, cross-sectional area and strainTP among the groups. However, stiffness
      and Young's modulus in after PHV groups were significantly higher than those of
      elementary school boys and before PHV groups (p <= 0.05). CONCLUSIONS: These
      results indicate that mechanical properties of Achilles tendon change
      dramatically at and/or around PHV to increased stiffness. The widely believed
      assumption that muscle-tendon unit is passively stretched due to rapid bone
      growth in adolescence is not supported.

PMID- 29177723
TI  - Intimate Partner Violence, Cumulative Violence Exposure, and Mental Health
      Service Use.
AB  - Intimate partner violence (IPV) leaves victims with serious mental
      healthconsequences; some victims do not seek help even though they suffer from
      adverse mental health symptoms. Victims' use of mental health services seems to
      be affected by sociocultural factors and their history of experiences with
      violence. This study used the collaborative psychiatric epidemiology surveys to
      examine the effects of cumulative violence on IPV victims' mental health service
      use. The results showed that victims' mental health needs were the most prominent
      predictor of their use of mental health services, and that cumulative violence
      exposure also predicted mental health service use.

PMID- 29177724
TI  - Cost Analysis of Community Based Family Support of Patients with Severe Mental
      Illness.
AB  - Community-based family support is a new option to patients with severe mental
      illness in which the patient and a volunteer family meet on a regular basic. This
      study examined whether this support could reduce patients' use of psychiatric
      services. This matched case-control study included 86 patients with severe mental
      illness. 40 patients were offered the intervention: community-based family
      support intervention. Patients' use of psychiatric hospital services was followed
      from 2 years before to 2 years after the intervention using a difference-in
      difference analytical approach. Although community-based family support seemed to
      reduce hospital admission, the reduction in cost did not compensate the cost of
      the programme. However, this does not rule out the potential cost effectiveness,
      and future studies should assess the clinical benefits and cost effectiveness of
      community-based family support. The present study does not provide sufficient
      basis for recommending the general implementation of community-based family
      support.

PMID- 29177725
TI  - Stigma Towards Depression in Rural Ireland: A Qualitative Exploration.
AB  - The configuration of one's social environment influences the course and
      experience of depression. Research suggests that experiencing depression is
      associated with stigmatisation and the concomitant experiencing of discrimination
      across many facets of social life. This is identified as a particularly important
      factor in rural communities. Contemporary work is absent in relation to
      understanding the stigma towards depression in Ireland, and its manifestation in
      rural Ireland specifically. Evidence is presented which suggests that depression
      is a significant source of stigmatisation in this setting, and that entrenched
      views centring upon disability and fear are prevalent.

PMID- 29177727
TI  - Effects of shape, size, and pyrene doping on electronic properties of graphene
      nanoflakes.
AB  - Effects of size, shape, and pyrene doping on electronic properties of graphene
      nanoflakes (GNFs) were theoretically investigated using density functional theory
      method with PBE, B3PW91, and M06-2X functionals and cc-pVDZ basis set. Two shapes
      of zigzag GNFs, hexagonal (HGN) and rhomboidal (RGN), were considered. The energy
      band gap of GNF depends on shape and decreases with size. The HGN has larger band
      gap energy (1.23-3.96 eV) than the RGN (0.13-2.12 eV). The doping of pyrene and
      pyrene derivatives on both HGN and RGN was also studied. The adsorption energy of
      pyrene and pyrene derivatives on GNF does not depend on the shape of GNFs with
      energies between 21 and 27 kcal mol-1. The substituent on pyrene enhances the
      binding to GNF but the strength does not depend on electron withdrawing or
      donating capability. The doping by pyrene and pyrene derivatives also shifts the
      HOMO and LUMO energies of GNFs. Both positive (destabilizing) and negative
      (stabilizing) shifts on HOMO and LUMO of GNFs were seen. The direction and
      magnitude of the shift do not follow the electron withdrawing and donating
      capability of pyrene substituents. However, only a slight shift was observed for
      doped RGN. A shift of 0.19 eV was noticed for HOMO of HGN doped with 1
      aminopyrene (pyNH2) and of 0.04 eV for LUMO of HGN doped with 1-pyrenecarboxylic
      acid (pyCOOH). Graphical Abstract HOMO and LUMO Energies of pyrene/pyrene
      derivatives doped Graphene Nanoflakes.

PMID- 29177728
TI  - Prognostic value of pre-treatment 18F-FDG PET uptake for nasopharyngeal
      carcinoma.
AB  - PURPOSE: To evaluate the prognostic value of maximal standardized uptake values
      (SUVmax) from serial fluor-18-fluorodeoxyglucose positron emission
      tomography/computed tomography (18F-FDG PET/CT) in patients with nasopharyngeal
      carcinoma (NPC). MATERIALS AND METHODS: Fifty-two patients with NPC who underwent
      18F-FDG PET/CT scan before radiotherapy with/without chemotherapy were reviewed
      retrospectively. Twenty-seven patients (52%) were applied 3-D conformal
      radiotherapy and 25 patients (48%) applied intensity-modulated radiotherapy
      (IMRT). Fourteen (27%) patients were given neoadjuvant chemotherapy and forty
      four (84.6%) patients were given concomitant and adjuvant chemotherapy. RESULTS:
      Median follow-up time was 34 months (range 5.6-66.4 months). Forty-four (84.6%)
      patients were alive at last follow-up and eight (15.4%) had died. The best cut
      off value of the SUVmax for the primary tumor site (SUVmax-PT) was 13 and 9 for
      the lymph nodes (SUVmax-LN). Patients with SUVmax-PT >= 13.0 and SUVmax-LN >= 9
      had a significantly higher risk for the development of the distant metastases (p
      = 0.044 and p = 0.038). DFS was affected in patients with SUVmax-PT >= 13 (log
      rank chi 2 = 2.54, p = 0.017) and was significantly lower in patients with SUVmax
      LN >= 9 for the lymph nodes (log rank chi 2 = 5.81, p = 0.013). OS was not
      affected by SUV levels. A multivariate Cox proportional hazard model of DFS
      included age (>= 40), SUVmax-LN (< 9), T stage (T1-2) and neoadjuvant
      chemotherapy are significantly better prognosis for the DFS. CONCLUSION: 18F-FDG
      PET/CT uptake before treatment, as determined by SUVmax, may be a valuable tool
      to evaluate prognosis in NPC patients.

PMID- 29177729
TI  - The effect of dietary energy and protein levels on body weight, size, and
      microflora of ostrich chicks.
AB  - The aim of this study was to evaluate the effect of different dietary energy and
      protein supplements on performance, weekly body sizes or body frame size, and
      microbiota of ostrich chicks during 2-9 weeks of age. Two metabolic energy levels
      of 2400 and 2600 kcal/kg live weight and three protein levels of 20, 22, and 24%
      were used. A total of 36 ostrich chickens (Struthio camelus) of the blue and
      black African breed were used. Body weight, 12 body measurements (i.e.,
      circumference of the head, neck, breast, abdomen, thigh, body height, length of
      tail, list the other 5 here) and excretion of microbial population (Escherichia
      coli, Coliforms bacteria, and Lactobacillus bacteria) were measured. Mean body
      weight in each week of the experiment was generally the lowest when chicks were
      offered 2600 kcal/kg dietary energy and 24% protein. Of the 12 body measurements,
      the breast, abdomen, and thigh circumference and also body length were greater at
      the lower energy (2400 kcal/kg) and higher protein (24%) levels. Total Aerobic
      bacteria excretion was generally lower in response to the diet containing the
      higher level of energy. We conclude that ostrich chickens during 2-9 weeks of age
      can grow on diets that contain lower energy levels.

PMID- 29177730
TI  - Type IA DNA Topoisomerases: A Universal Core and Multiple Activities.
AB  - All the type IA topoisomerases display universal characteristics relying on a
      core region basically responsible for the transesterification and the strand
      passage reaction. First limited to the bacterial domain for a long time, these
      enzymes were further retrieved in Archaea and Eukarya as well. This is
      representative of an extremely ancient origin, probably due to an inheritance
      from the RNA world. As remaining evidence, some current topoisomerases IA have
      retained a RNA topoisomerase activity. Despite the presence of this core region
      in all of these TopoIAs, some differences exist and are originated from variable
      regions, located essentially within both extremities, conferring on them their
      specificities. During the last 2 decades the evidence of multiple activities and
      dedicated roles highlighted the importance of the topoisomerases IA. It is now
      obvious that topoisomerases IA are key enzymes involved in the maintenance of the
      genome stability. The discovery of these new activities was done thanks to the
      use of more accurate assays, based on new sophisticated DNA substrates.

PMID- 29177731
TI  - Topoisomerase I and Genome Stability: The Good and the Bad.
AB  - Topoisomerase I (Top1) resolves torsional stress that accumulates during
      transcription, replication and chromatin remodeling by introducing a transient
      single-strand break in DNA. The cleavage activity of Top1 has opposing roles,
      either promoting or destabilizing genome integrity depending on the context.
      Resolution of transcription-associated negative supercoils, for example, prevents
      pairing of the nascent RNA with the DNA template (R-loops) as well as DNA
      secondary structure formation. Reduced Top1 levels thus enhance CAG repeat
      contraction, somatic hypermutation, and class switch recombination. Actively
      transcribed ribosomal DNA is also destabilized in the absence of Top1, reflecting
      the importance of Top1 in ensuring efficient transcription. In terms of promoting
      genome instability, an aborted Top1 catalytic cycle stimulates deletions at short
      tandem repeats and the enzyme's transesterification activity supports
      illegitimate recombination. Finally, Top1 incision at ribonucleotides embedded in
      DNA generates deletions in tandem repeats, and induces gross chromosomal
      rearrangements and mitotic recombination.

PMID- 29177732
TI  - DNA Topoisomerases as Targets for Antibacterial Agents.
AB  - DNA topoisomerases are proven therapeutic targets of antibacterial agents.
      Quinolones, especially fluoroquinolones, are the most successful topoisomerase
      targeting antibacterial drugs. These drugs target type IIA topoisomerases in
      bacteria. Recent structural and biochemical studies on fluoroquinolones have
      provided the molecular basis for both their mechanism of action, as well as the
      molecular basis of bacterial resistance. Due to the development of drug
      resistance, including fluoroquinolone resistance, among bacterial pathogens,
      there is an urgent need to discover novel antibacterial agents. Recent advances
      in topoisomerase inhibitors may lead to the development of novel antibacterial
      drugs that are effective against fluoroquinolone-resistant pathogens. They
      include type IIA topoisomerase inhibitors that either interact with the GyrB/ParE
      subunit or form nick-containing ternary complexes. In addition, several
      topoisomerase I inhibitors have recently been identified. Thus, DNA
      topoisomerases remain important targets of antibacterial agents.

PMID- 29177733
TI  - DNA Supercoiling Measurement in Bacteria.
AB  - DNA supercoiling plays critical roles in several essential DNA metabolic
      pathways, such as replication, transcription and recombination. Typically plasmid
      DNA molecules are used to measure DNA supercoiling status inside bacterial cells.
      In this chapter, we describe how to isolate plasmid DNA molecules from E. coli
      cells and determine DNA supercoiling density by 1% agarose gel electrophoresis
      containing chloroquine using plasmid pACYC184 as an example.

PMID- 29177734
TI  - DNA Catenation Reveals the Dynamics of DNA Topology During Replication.
AB  - Two-dimensional agarose gel electrophoresis is the method of choice to identify
      and quantify all the topological forms DNA molecules can adopt in vivo. Here we
      describe the materials and protocols needed to analyze catenanes, the natural
      outcome of DNA replication, in Saccharomyces cerevisiae. We describe the
      formation of pre-catenanes during replication and how inhibition of topoisomerase
      2 leads to the accumulation of intertwined sister duplexes. This knowledge is
      essential to determine how replication forks blockage or pausing affects the
      dynamic of DNA topology during replication.

PMID- 29177735
TI  - Mapping E. coli Topoisomerase IV Binding and Activity Sites.
AB  - This methods article described a protocol aiming at mapping E. coli Topoisomerase
      IV (Topo IV) binding and cleavage activity sites on the genome. The approach is
      readily applicable to any Type II topoisomerase on a broad variety of gram
      positive and gram-negative bacterial species. Conventional ChIP-seq of flag
      tagged Topo IV subunits and a novel method aimed at trapping only DNA bound to
      active Topo IV (called NorfliP) are described. NorfliP relies on the ability of
      norfloxacin, a quinolone drug, to cross-link the 5' ends of the DNA breaks with
      the catalytic tyrosine of bacterial Type II topoisomerases. These methods give
      complementary results and their combination brought important insights on both
      the function and regulation of Topo IV.

PMID- 29177736
TI  - The Use of Psoralen Photobinding to Study Transcription-Induced Supercoiling.
AB  - Proteins manipulating intracellular DNA necessarily impart torsional stress,
      which redistributes across the DNA. Overtwisting and undertwisting of the double
      helix result in the manifestation of positive and negative DNA supercoiling. A
      growing body of evidence indicates that DNA topology is an important player in
      the key regulatory steps of genome function, highlighting the need for
      biochemical techniques to detect dynamic changes in the DNA structure. Psoralen
      binding to DNA in vivo is proportional to the level of supercoiling, providing an
      excellent probe for the topological state of nuclear DNA. Here we describe a
      psoralen-based methodology to detect transcription-induced DNA supercoiling
      genome-wide. The DNA samples generated with this approach can be hybridized to
      microarray platforms or high-throughput sequenced to provide a topological
      snapshot of the whole genome.

PMID- 29177737
TI  - Immunoprecipitation of RNA:DNA Hybrids from Budding Yeast.
AB  - During transcription, the nascent transcript behind an elongating RNA polymerase
      (RNAP) can invade the DNA duplex and hybridize with the complementary DNA
      template strand, generating a three-stranded "R-loop" structure, composed of an
      RNA:DNA duplex and an unpaired non-template DNA strand. R-loops can be strongly
      associated with actively transcribed loci by all RNAPs including the
      mitochondrial RNA polymerase (mtRNAP). In this chapter, we describe two protocols
      for the detection of RNA:DNA hybrids in living budding yeast cells, one that uses
      conventional chromatin immunoprecipitation (ChIP-qPCR) and one that uses DNA:RNA
      immunoprecipitation (DRIP-qPCR). Both protocols make use of the S9.6 antibody,
      which is believed to recognize the intermediate A/B helical RNA:DNA duplex
      conformation, with no sequence specificity.

PMID- 29177738
TI  - Detection of oriC-Independent Replication in Escherichia coli Cells.
AB  - In bacteria, replication of the chromosome is normally initiated following the
      binding of DnaA proteins to the oriC region. However, under certain
      circumstances, replication can also be initiated independent of the oriC/DnaA
      system. This is the case, for example, in Escherichia coli cells lacking RNase HI
      (rnha mutants) or type 1A topoisomerase activity (topA topB mutants). Here, we
      present a protocol in which replication from the oriC/DnaA system is first
      inhibited by the addition of the protein synthesis inhibitor, spectinomycin, to
      exponentially growing bacterial cell cultures. The thymidine analog, 5-ethynyl-2'
      deoxyurdine (EdU) is then added to the cells, and after 1 h the cells are fixed
      and the Alexa Fluor(r) 488 dye is conjugated to EdU by the click-iT(r) reaction.
      The oriC-independent replication is detected in fixed cells by flow cytometry and
      can be visualized by fluorescence microscopy.

PMID- 29177739
TI  - Single-Molecule Magnetic Tweezer Analysis of Topoisomerases.
AB  - Magnetic tweezers (MT) provide a powerful single-molecule approach to study the
      mechanism of topoisomerases, giving the experimenter the ability to change and
      read out DNA topology in real time. By using diverse DNA substrates, one can
      study different aspects of topoisomerase function and arrive at a better
      mechanistic understanding of these fascinating enzymes. Here we describe methods
      for the creation of three different DNA substrates used in MT experiments with
      topoisomerases: double-stranded DNA (dsDNA) tethers, "braided" (intertwined or
      catenated) DNA tether pairs, and dsDNA tethers with single-stranded DNA (ssDNA)
      regions. Additionally, we discuss how to build flow cells for bright-field MT
      microscopy, as well as how to noncovalently attach anti-digoxigenin to the
      coverslip surface for tethering digoxigenin-labeled DNAs. Finally, we describe
      procedures for the identification of a suitable DNA substrate for MT study and
      data collection.

PMID- 29177740
TI  - Synthesis of Hemicatenanes for the Study of Type IA Topoisomerases.
AB  - Hemicatenane is a structure that forms when two DNA duplexes are physically
      linked through a single-stranded crossover. It is proposed to be an intermediate
      resulting from double Holliday junction (dHJ) dissolution, repair of replication
      stalled forks and late stage replication. Our previous study has shown that
      hemicatenane can be synthesized and dissolved in vitro by hyperthermophilic type
      IA topoisomerases. Here we present the protocol of hemicatenane synthesis and its
      structure detection by 2D agarose gel electrophoresis. The generated product can
      be used as a substrate to study the biochemical mechanism of hemicatenane
      processing reactions.

PMID- 29177741
TI  - An Assay for Detecting RNA Topoisomerase Activity.
AB  - RNA topoisomerase activity has recently been detected in multiple Type IA DNA
      topoisomerases from all three domains of life: bacteria, archaea, and eukarya.
      Many, but not all, Type IA topoisomerases are found to possess activities for not
      only DNA, but also RNA, suggesting that they may solve topological problems for
      both types of nucleic acids. Here we describe a detailed assay used by our group
      to detect RNA topoisomerase activity for many Type IA topoisomerases. We discuss
      the strategy, experimental procedures, troubleshooting, and limitations for this
      assay.

PMID- 29177742
TI  - Studying TDP1 Function in DNA Repair.
AB  - Topoisomerase poisons act by inducing abortive topoisomerase reactions, which
      generate stable protein-DNA breaks (PDBs) that interfere with transcription
      elongation and progression of replication forks. In vertebrates, Tyrosyl-DNA
      phosphodiesterase 1 (TDP1) plays a major role in removal of topoisomerase 1
      associated PDBs in the nucleus and mitochondria by hydrolyzing the 3'
      phosphotyrosine bond. Depletion of TDP1 sensitizes tumor cells with defective DNA
      repair capacity to the genotoxic effect of TOP1 poisons, while homozygous
      mutation of the catalytic residue of TDP1 is associated with cerebellar
      degeneration and ataxia. We describe here two fluorescence based biochemical
      assays for measuring TDP1 phosphodiesterase activity in cellular lysates. The
      Gyrasol assay is sensitive, high-throughput, and useful for screening potential
      TDP1 inhibitors or cell lines that are likely to develop resistance to TOP1
      poisons. The gel-shift assay is low cost and simple to set up, and is also
      suitable for screening cell lines that are likely to develop resistance to TOP1
      poisons, as well as for diagnostic screening for individuals with hereditary
      ataxias.

PMID- 29177743
TI  - Topoisomerase II Chromatin Immunoprecipitation.
AB  - Chromatin immunoprecipitation is a method to isolate a protein of interest
      coupled to DNA following cross-linking with formaldehyde and to quantify the
      relative abundance or occupancy of the protein at specific genomic loci. After
      immunoprecipitation of protein-DNA complexes protein-DNA cross-links are reversed
      and the DNA is extracted. Various methods exist to identify binding sites and
      determine relative occupancy of the protein of interest; these include
      quantitative PCR, probing microarrays or sequencing the isolated DNA (ChIP-seq).
      This chapter details the method of chromatin immunoprecipitation of TOP2 to the
      point of DNA extraction from the precipitated protein-DNA complexes.

PMID- 29177744
TI  - Analyzing Mitotic Chromosome Structural Defects After Topoisomerase II Inhibition
      or Mutation.
AB  - For analyzing chromosome structural defects that result from topoisomerase II
      (topo II) dysfunction we have adapted classical cell cycle experiments, classical
      cytological techniques and the use of a potent topo II inhibitor (ICRF-193). In
      this chapter, we describe in detail the protocols used and we discuss the
      rational for our choice and for the adaptations applied. We clarify in which cell
      cycle stages each of the different chromosomal aberrations induced by inhibiting
      topo II takes place: lack of chromosome segregation, undercondensation, lack of
      sister chromatid resolution, and lack of chromosome individualization. We also
      put these observations into the context of the two topo II-dependent cell cycle
      checkpoints. In addition, we have devised a system to analyze phenotypes that
      result when topo II is mutated in human cells. This serves as an alternative
      strategy to the use of topo II inhibitors to perturb topo II function.

PMID- 29177745
TI  - Monitoring the DNA Topoisomerase II Checkpoint in Saccharomyces cerevisiae.
AB  - Topoisomerase II activity is crucial to maintain genome stability through the
      removal of catenanes in the DNA formed during DNA replication and scaffolding the
      mitotic chromosome. Perturbed Topo II activity causes defects in chromosome
      segregation due to persistent catenations and aberrant DNA condensation during
      mitosis. Recently, novel top2 alleles in the yeast Saccharomyces cerevisiae
      revealed a checkpoint control which responds to perturbed Topo II activity.
      Described in this chapter are protocols for assaying the phenotypes seen in top2
      mutants on a cell biological basis in live cells: activation of the Topo II
      checkpoint using spindle morphology, chromosome condensation using fluorescently
      labeled chromosomal loci and cell cycle progression by flow cytometry. Further
      characterization of this novel checkpoint is warranted so that we can further our
      understanding of the cell cycle, genomic stability, and the possibility of
      identifying novel drug targets.

PMID- 29177746
TI  - Studying Topoisomerase 1-Mediated Damage at Genomic Ribonucleotides.
AB  - Ribonucleotides incorporated into DNA by the DNA polymerases can be incised by
      Topoisomerase 1 (Top1) to initiate removal of ribonucleotides from the genome.
      This Top1-dependent ribonucleotide removal has been demonstrated to result in
      multiple forms of genome instability in yeast. Here, we describe both
      quantitative and qualitative assays to identify mutations and other forms of DNA
      damage resulting from Top1-cleavage at unrepaired genomic ribonucleotides.

PMID- 29177747
TI  - A Fluorescence-Based Assay for Identification of Bacterial Topoisomerase I
      Poisons.
AB  - Bacterial Topoisomerase I is a potential target for the identification of novel
      topoisomerase poison inhibitors that could provide leads for a new class of
      antibacterial compounds. Here we describe in detail a fluorescence-based cleavage
      assay that is successfully used in HTS for the discovery of bacterial
      topoisomerase Iota poisons.

PMID- 29177748
TI  - Fluoroquinolone-Gyrase-DNA Cleaved Complexes.
AB  - The quinolones are potent antibacterials that act by forming complexes with DNA
      and either gyrase or topoisomerase IV. These ternary complexes, called cleaved
      complexes because the DNA moiety is broken, block replication, transcription, and
      bacterial growth. Cleaved complexes readily form in vitro when gyrase, plasmid
      DNA, and quinolone are combined and incubated; complexes are detected by the
      linearization of plasmid DNA, generally assayed by gel electrophoresis. The
      stability of the complexes can be assessed by treatment with EDTA, high
      temperature, or dilution to dissociate the complexes and reseal the DNA moiety.
      Properties of the complexes are sensitive to quinolone structure and to
      topoisomerase amino acid substitutions associated with quinolone resistance.
      Consequently, studies of cleaved complexes can be used to identify improvements
      in quinolone structure and to understand the biochemical basis of target-based
      resistance. Cleaved complexes can also be detected in quinolone-treated bacterial
      cells by their ability to rapidly block DNA replication and to cause chromosome
      fragmentation; they can even be recovered from lysed cells following CsCl density
      gradient centrifugation. Thus, in vivo and cell-fractionation tests are available
      for assessing the biological relevance of work with purified components.

PMID- 29177749
TI  - Detection of Topoisomerase Covalent Complexes in Eukaryotic Cells.
AB  - DNA topoisomerases carry out topological transformations of DNA by introducing
      transient DNA breaks. The covalent intermediate of topoisomerase reactions
      include the topoisomerase protein covalently bound to DNA by a phosphotyrosine
      intermediate. Anti-cancer drugs that target topoisomerases typically trap the
      covalent intermediate, and generate cytotoxic enzyme dependent DNA damage. More
      recently, structural alterations in DNA such as DNA damage have also been shown
      to trap covalent intermediates of topoisomerase reactions. Understanding the
      action of drugs that target topoisomerases as well as determining the importance
      of trapped topoisomerases on genome stability requires assays that can accurately
      and sensitively measure levels of topoisomerase/DNA complexes. This chapter
      describes two approaches that have been developed to quantitate topoisomerase DNA
      complexes. These assays termed ICE (in vivo complex of enzymes) and RADAR (rapid
      approach to DNA adduct recovery) rely on isolation of genomic DNA under
      conditions that preserve proteins covalently bound to DNA. Covalently bound
      proteins are then quantitated using antibodies directed against specific
      topoisomerases. We describe assays in both mammalian cells and the yeast
      Saccharomyces cerevisiae that can measure topoisomerase/DNA covalent complexes,
      and give examples that can be used to enhance the quantitative reliability of
      these assays.

PMID- 29177750
TI  - Visualization and Quantification of Topoisomerase-DNA Covalent Complexes Using
      the Trapped in Agarose Immunostaining (TARDIS) Assay.
AB  - The TARDIS assay was originally developed as a means of detecting and quantifying
      melphalan and cisplatin DNA adducts at the single cell level, but it has since
      been adapted to quantify topoisomerase DNA complexes that result from the actions
      of topoisomerase poisons and this is currently the main use of the assay. The
      method employs sensitive immunofluorescent detection to quantify topoisomerase
      molecules covalently coupled to DNA in what are often referred to as cleavage
      complexes. Free topoisomerase molecules, and other cellular constituents are
      first removed using salt-detergent extraction of agarose-embedded, unfixed cells.
      Using these stringent extraction conditions, genomic DNA remains in place in the
      agarose as "nuclear ghosts," and any covalent attached molecules can be detected
      and quantified by immunofluorescence with a low background.

PMID- 29177751
TI  - Study of Plasmid-Mediated Quinolone Resistance in Bacteria.
AB  - Plasmid-mediated quinolone resistance (PMQR) involves genes for proteins that
      protect the quinolone targets, an enzyme that inactivates certain quinolones as
      well as aminoglycosides, and pumps that efflux quinolones. Quinolone
      susceptibility is reduced by these mechanisms but not to the level of clinical
      resistance unless chromosomal mutations are also present. PCR primers and
      conditions for PMQR gene detection are described as well as how to establish a
      plasmid location.

PMID- 29177752
TI  - Bacterial Shifts in Nutrient Solutions Flowing Through Biofilters Used in Tomato
      Soilless Culture.
AB  - In soilless culture, slow filtration is used to eliminate plant pathogenic
      microorganisms from nutrient solutions. The present study focused on the
      characterization and the potential functions of microbial communities colonizing
      the nutrient solutions recycled on slow filters during a whole cultivation season
      of 7 months in a tomato growing system. Bacterial microflora colonizing the
      solutions before and after they flew through the columns were studied. Two
      filters were amended with Pseudomonas putida (P-filter) or Bacillus cereus
      strains (B-filter), and a third filter was a control (C-filter). Biological
      activation of filter unit through bacterial amendment enhanced very significantly
      filter efficacy against plant potential pathogens Pythium spp. and Fusarium
      oxysporum. However, numerous bacteria (103-104 CFU/mL) were detected in the
      effluent solutions. The community-level physiological profiling indicated a
      temporal shift of bacterial microflora, and the metabolism of nutrient solutions
      originally oriented towards carbohydrates progressively shifted towards
      degradation of amino acids and carboxylic acids over the 7-month period of
      experiment. Single-strand conformation polymorphism fingerprinting profiles
      showed that a shift between bacterial communities colonizing influent and
      effluent solutions of slow filters occurred. In comparison with influent, 16S
      rDNA sequencing revealed that phylotype diversity was low in the effluent of P-
      and C-filters, but no reduction was observed in the effluent of the B-filter.
      Suppressive potential of solutions filtered on a natural filter (C-filter), where
      the proportion of Proteobacteria (alpha- and beta-) increased, whereas the
      proportion of uncultured candidate phyla rose in P- and B-filters, is discussed.

PMID- 29177753
TI  - Microbial Reduction of Fe(III) and SO42- and Associated Microbial Communities in
      the Alluvial Aquifer Groundwater and Sediments.
AB  - Agricultural demands continuously increased use of groundwater, causing drawdown
      of water table and need of artificial recharge using adjacent stream waters.
      River water intrusion into groundwater can alter the geochemical and
      microbiological characteristics in the aquifer and subsurface. In an effort to
      investigate the subsurface biogeochemical activities before operation of
      artificial recharge at the test site, established at the bank of Nakdong River,
      Changwon, South Korea, organic carbon transported from river water to groundwater
      was mimicked and the effect on the indigenous microbial communities was
      investigated with the microcosm incubations of the groundwater and subsurface
      sediments. Laboratory incubations indicated microbial reduction of Fe(III) and
      sulfate. Next-generation Illumina MiSeq sequences of V4 region of 16S rRNA gene
      provided that the shifts of microbial taxa to Fe(III)-reducing and/or sulfate
      reducing microorganisms such as Geobacter, Albidiferax, Desulfocapsa,
      Desulfuromonas, and Desulfovibrio were in good correlation with the sequential
      flourishment of microbial reduction of Fe(III) and sulfate as the incubations
      progressed. This suggests the potential role of dissolved organic carbons
      migrated with the river water into groundwater in the managed aquifer recharge
      system on the indigenous microbial community composition and following
      alterations of subsurface biogeochemistry and microbial metabolic activities.

PMID- 29177755
TI  - Are cytological parameters of maize landraces (Zea mays ssp. mays) adapted along
      an altitudinal cline?
AB  - The Northwestern Argentina (NWA) highland region is one of the southernmost areas
      of native maize cultivation. We studied variations of different cytological
      parameters, such as DNA contents, presence/absence of B chromosomes (Bs), and
      number and sequence composition of heterochromatic knobs in ten accessions of
      four maize landraces growing along a broad altitudinal cline in NWA. The aim of
      this work was to assess variations in cytological parameters and their
      relationship with the crop altitude of cultivation, in an adaptive context. The A
      DNA content of the A chromosome complements showed 40% of difference between the
      lowest (4.5 pg) and the highest (6.3 pg) 2C value. This variation could be
      attributed to differences in number and size of heterochromatic knobs.
      Fluorescent in situ hybridization studies revealed the sequence composition of
      each knob, with a higher proportion of knobs composed of 180-bp repeats rather
      than TR-1 repeats, in all accessions. We also found numerical polymorphisms and
      the highest frequency of Bs reported in maize to this date. These results lead us
      to propose that the frequencies and doses of Bs are influenced by the landrace
      genotypical make-up. The Bs might be maintained in higher frequencies in those
      accessions having lower heterochromatin content, so as to preserve an optimal
      nucleotype. Furthermore, selective forces acting along the altitudinal gradient
      might be modulating the cytological parameters studied, as suggested by the
      significant correlations found among them.

PMID- 29177754
TI  - A review of biomarkers in peri-miniscrew implant crevicular fluid (PMICF).
AB  - BACKGROUND: The temporary anchorage devices (TADs) which include miniscrew
      implants (MSIs) have evolved as useful armamentarium in the management of severe
      malocclusions and assist in complex tooth movements. Although a multitude of
      factors is responsible for the primary and secondary stability of miniscrew
      implants, contemporary research highlights the importance of biological interface
      of MSI with bone and soft tissue in augmenting the success of implants. The
      inflammation and remodeling associated with MSI insertion or loading are
      reflected through biomarkers in peri-miniscrew implant crevicular fluid (PMICF)
      which is analogous to the gingival crevicular fluid. Analysis of biomarkers in
      PMICF provides indicators of inflammation at the implant site, osteoclast
      differentiation and activation, bone resorption activity and bone turnover. The
      PMICF for assessment of these biomarkers can be collected non-invasively via
      paper strips, periopaper or micro capillary pipettes and analysed by enzyme
      linked immunosorbent assay (ELISA) or immunoassays. The markers and mediators of
      inflammation have been previously studied in relation to orthodontic tooth
      movement include interleukins (IL-1beta, IL-2, IL-6 and IL-8), growth factors and
      other proteins like tumour necrosis factor (TNF-alpha), receptor activator of
      nuclear factor kappa-B ligand (RANKL), chondroitin sulphate (CS) and
      osteoprotegerin (OPG). Studies have indicated that successful and failed MSIs
      have different concentrations of biomarkers in PMICF. However, there is a lack of
      comprehensive information on this aspect of MSIs. Therefore, a detailed review
      was conducted on the subject. RESULTS: A literature search revealed six relevant
      studies: two on IL-1beta; one on IL-2, IL-6 and IL-8; one on TNF-alpha; one on
      CS; and one on RANKL/OPG ratio. One study showed an increase in IL-1beta levels
      upon MSI loading, peak in 24 hours (h), followed by a decrease in 21 days to
      reach baseline in 300 days. A 6.87% decrease in IL-2 levels was seen before
      loading and a 5.97% increase post-loading. IL-8 showed a 6.31% increase after
      loading and IL-6 increased by 3.08% before MSI loading and 15.06% after loading.
      RANKL/OPG ratio increased in loaded compared to unloaded MSIs. CONCLUSIONS:
      Cytokines (mainly ILs and TNF-alpha) and RANKL/OPG ratio showed alteration in
      PMICF levels upon loading of MSIs as direct or indirect anchorage.

PMID- 29177756
TI  - Leucocin C-607, a Novel Bacteriocin from the Multiple-Bacteriocin-Producing
      Leuconostoc pseudomesenteroides 607 Isolated from Persimmon.
AB  - Leuconostoc pseudomesenteroides 607, isolated from persimmon fruit, was found to
      have high inhibitory activity against Listeria monocytogenes and several other
      Gram-positive bacteria. Inhibitory substances were purified from culture
      supernatant by ion-exchange chromatography, Sep-Pak C18 cartridge, and reverse
      phase high-performance liquid chromatography (RP-HPLC). Two antibacterial
      peptides were observed during the purification procedures. One of these peptides
      had a molecular size of 4623.05 Da and a partial N-terminal amino acid sequence
      of NH2-KNYGNGVHxTKKGxS, in which the YGNGV motif is specific for class IIa
      bacteriocins. A BLAST search revealed that this bacteriocin was similar to
      leucocin C from Leuconostoc mesenteroides. Leucocin C-specific primers were
      designed and a single PCR product was amplified. Analysis of the nucleotide
      sequence has revealed a putative peptide differing by only one amino acid residue
      from the sequence of leucocin C. No identical peptide or protein has been
      reported in the literature, and this peptide, termed leucocin C-607, was
      therefore considered to be a new variant of leucocin C produced by Leuc.
      pseudomesenteroides 607. Another antibacterial peptide purified from the same
      culture supernatant had a molecular size of 3007.7 or 3121.97 Da. However,
      detailed information regarding this second peptide remains to be determined.
      Distinct characteristics, such as heat stability and inhibitory spectrum, were
      observed for the two bacteriocins produced by Leuc. pseudomesenteroides 607.
      These results suggested that Leuc. pseudomesenteroides 607 produces leucocin C
      607 along with another unknown bacteriocin.

PMID- 29177757
TI  - The role of dermoscopy in the diagnosis of distal lateral subungual
      onychomycosis.
AB  - Recently dermoscopic patterns, that can be useful in the diagnosis of distal and
      lateral subungual onychomycosis, were identified. In this study, we aimed to
      determine the frequency of the defined patterns so far and additionally to
      identify other patterns that were observed and to investigate the place of these
      patterns in the diagnosis of Distal Lateral Subungual Onychomycosis (DLSO) in the
      dermoscopic examination of the patients with pre-diagnosis of DLSO. Patients
      admitted dermatology outpatient clinic of Haydarpasa Numune Training and Research
      Hospital with the complaint of nail disturbance suspicious for DLSO (97 patients)
      between the August 2015 and February 2016. Clinical and dermoscopic photographs
      of the cases with a pre-diagnosis of DLSO were taken and their nails were cut for
      pathological examination and culture. In hematoxylin and eosin, and periodic acid
      schiff examination, hyphe and/or spore were observed in 134 (65.4%) and fungal
      growth was detected in 99 (48.3%) of the nail samples. As a result of logistic
      regression model analysis, the p values of the 'ruin appearance', 'homogeneous
      leukonychia', 'punctate leukonychia', and 'black discoloration' patterns
      preserved their statistical significance (p = 0.015, p = 0.009, p = 0.026, p =
      0.040, respectively). We believe that in nail disorders clinically resembling
      DLSO patients, the presence of dermoscopic patterns of ruin appearance,
      homogenous leuconychia, punctate leuconychia, and black discoloration strongly
      supports the clinical diagnosis of DLSO.

PMID- 29177758
TI  - Reducing COPD readmissions through predictive modeling and incentive-based
      interventions.
AB  - This paper introduces a case study at a community hospital to develop a
      predictive model to quantify readmission risks for patients with chronic
      obstructive pulmonary disease (COPD), and use it to support decision making for
      appropriate incentive-based interventions. Data collected from the community
      hospital's database are analyzed to identify risk factors and a logistic
      regression model is developed to predict the readmission risk within 30 days post
      discharge of an individual COPD patient. By targeting on the high-risk patients,
      we investigate the implementability of the incentive policy which encourages
      patients to take interventions and helps them to overcome the compliance barrier.
      Specifically, the conditions and scenarios are identified for either achieving
      the desired readmission rate while minimizing the total cost, or reaching the
      lowest readmission rate under incentive budget constraint. Currently, such models
      are under consideration for a pilot study at the community hospital.

PMID- 29177760
TI  - Introduction.
AB  - In this special volume on "Chromatin regulation of early embryonic lineage
      specification," five leaders in the field of mammalian preimplantation embryo
      development provide their own perspectives on key molecular and cellular
      processes that mediate lineage formation during the first week of life. The first
      cell-fate decision involves the formation of the pluripotent inner cell mass
      (ICM) and extraembryonic trophectoderm (TE). The second cell-fate choice
      encompasses the transformation of ICM into extraembryonic primitive endoderm (PE)
      and pluripotent epiblast. The processes, which occur during the period of
      preimplantation development, serve as the foundation for subsequent developmental
      events such as implantation, placentation, and gastrulation. The mechanisms that
      regulate them are complex and involve many different factors operating spatially
      and temporally over several days to modulate embryonic chromatin structure,
      impose cellular polarity, and direct distinct gene expression programs in the
      first cell lineages.

PMID- 29177759
TI  - Personality and eating and weight disorders: an open research challenge.

PMID- 29177761
TI  - Chromatin Remodelling Proteins and Cell Fate Decisions in Mammalian
      Preimplantation Development.
AB  - The very first cell divisions in mammalian embryogenesis produce a ball of cells,
      each with the potential to form any cell in the developing embryo or placenta. At
      some point, the embryo produces enough cells that some are located on the outside
      of the embryo, while others are completely surrounded by other cells. It is at
      this point that cells undergo the very first lineage commitment event: outer
      cells form the trophectoderm and lose the potential to form embryonic lineages,
      while inner cells form the Inner Cell Mass, which retain embryonic potential.
      Cell identity is defined by gene expression patterns, and gene expression is
      largely controlled by how the DNA is packaged into chromatin. A number of protein
      complexes exist which are able to use the energy of ATP to remodel chromatin:
      that is, to alter the nucleosome topology of chromatin. Here, we summarise the
      evidence that chromatin remodellers play essential roles in the successful
      completion of preimplantation development in mammals and describe recent efforts
      to understand the molecular mechanisms through which chromatin remodellers
      facilitate the successful completion of the first cell fate decisions in
      mammalian embryogenesis.

PMID- 29177762
TI  - CHD1 Controls Cell Lineage Specification Through Zygotic Genome Activation.
AB  - In mammals, the processes spanning from fertilization to the generation of a new
      organism are very complex and are controlled by multiple genes. Life begins with
      the encounter of eggs and spermatozoa, in which gene expression is inactive prior
      to fertilization. After several cell divisions, cells arise that are specialized
      in implantation, a developmental process unique to mammals. Cells involved in the
      establishment and maintenance of implantation differentiate from totipotent
      embryos, and the remaining cells generate the embryo proper. Although this
      process of differentiation, termed cell lineage specification, is supported by
      various gene expression networks, many components have yet to be identified.
      Moreover, despite extensive research it remains unclear which genes are
      controlled by each of the factors involved. Although it has become clear that
      epigenetic factors regulate gene expression, elucidation of the underlying
      mechanisms remains challenging. In this chapter, we propose that the chromatin
      remodeling factor CHD1, together with epigenetic factors, is involved in a subset
      of gene expression networks involved in processes spanning from zygotic genome
      activation to cell lineage specification.

PMID- 29177763
TI  - Transcriptional Regulation and Genes Involved in First Lineage Specification
      During Preimplantation Development.
AB  - The successful development from a single-cell zygote into a complex multicellular
      organism requires precise coordination of multiple cell-fate decisions. The very
      first of these is lineage specification into the inner cell mass (ICM) and
      trophectoderm (TE) during mammalian preimplantation development. In mouse
      embryos, transcription factors (TFs) such as Oct4, Sox2, and Nanog are enriched
      in cells of ICM, which gives rise to the fetus and yolk sac. Conversely, TFs such
      as Cdx2 and Eomes become highly upregulated in TE, which contribute to the
      placenta. Here, we review the current understanding of key transcriptional
      control mechanisms and genes responsible for these distinct differences during
      the first cell lineage specification. In particular, we highlight recent insights
      gained through advances in genome manipulation, live imaging, single-cell
      transcriptomics, and loss-of-function studies.

PMID- 29177765
TI  - XEN and the Art of Stem Cell Maintenance: Molecular Mechanisms Maintaining Cell
      Fate and Self-Renewal in Extraembryonic Endoderm Stem (XEN) Cell Lines.
AB  - The extraembryonic endoderm is one of the first cell types specified during
      mammalian development. This extraembryonic lineage is known to play multiple
      important roles throughout mammalian development, including guiding axial
      patterning and inducing formation of the first blood cells during embryogenesis.
      Moreover, recent studies have uncovered striking conservation between mouse and
      human embryos during the stages when extraembryonic endoderm cells are first
      specified, in terms of both gene expression and morphology. Therefore, mouse
      embryos serve as an excellent model for understanding the pathways that maintain
      extraembryonic endoderm cell fate. In addition, self-renewing multipotent stem
      cell lines, called XEN cells, have been derived from the extraembryonic endoderm
      of mouse embryos. Mouse XEN cell lines provide an additional tool for
      understanding the basic mechanisms that contribute to maintaining lineage
      potential, a resource for identifying how extraembryonic ectoderm specifies fetal
      cell types, and serve as a paradigm for efforts to establish human equivalents.
      Given the potential conservation of essential extraembryonic endoderm roles,
      human XEN cells would provide a considerable advance. However, XEN cell lines
      have not yet been successfully derived from human embryos. Given the potential
      utility of human XEN cell lines, this chapter focuses on reviewing the mechanisms
      known to govern the stem cell properties of mouse XEN, in hopes of facilitating
      new ways to establish human XEN cell lines.

PMID- 29177764
TI  - ROCK and RHO Playlist for Preimplantation Development: Streaming to HIPPO Pathway
      and Apicobasal Polarity in the First Cell Differentiation.
AB  - In placental mammalian development, the first cell differentiation produces two
      distinct lineages that emerge according to their position within the embryo: the
      trophectoderm (TE, placenta precursor) differentiates in the surface, while the
      inner cell mass (ICM, fetal body precursor) forms inside. Here, we discuss how
      such position-dependent lineage specifications are regulated by the RHOA
      subfamily of small GTPases and RHO-associated coiled-coil kinases (ROCK). Recent
      studies in mouse show that activities of RHO/ROCK are required to promote TE
      differentiation and to concomitantly suppress ICM formation. RHO/ROCK operate
      through the HIPPO signaling pathway, whose cell position-specific modulation is
      central to establishing unique gene expression profiles that confer cell fate. In
      particular, activities of RHO/ROCK are essential in outside cells to promote
      nuclear localization of transcriptional co-activators YAP/TAZ, the downstream
      effectors of HIPPO signaling. Nuclear localization of YAP/TAZ depends on the
      formation of apicobasal polarity in outside cells, which requires activities of
      RHO/ROCK. We propose models of how RHO/ROCK regulate lineage specification and
      lay out challenges for future investigations to deepen our understanding of the
      roles of RHO/ROCK in preimplantation development. Finally, as RHO/ROCK may be
      inhibited by certain pharmacological agents, we discuss their potential impact on
      human preimplantation development in relation to fertility preservation in women.

PMID- 29177766
TI  - Effect of solute immobilization on the stability problem within the fractional
      model in the solute analog of the Horton-Rogers-Lapwood problem.
AB  - The paper is devoted to the linear stability analysis within the solute analogue
      of the Horton-Rogers-Lapwood (HRL) problem. The solid nanoparticles are treated
      as solute within the continuous approach. Therefore, we consider the infinite
      horizontal porous layer saturated with a mixture (carrier fluid and solute).
      Solute transport in porous media is very often complicated by solute
      immobilization on a solid matrix of porous media. Solute immobilization (solute
      sorption) is taken into account within the fractal model of the MIM approach.
      According to this model a solute in porous media immobilizes within random time
      intervals and the distribution of such random variable does not have a finite
      mean value, which has a good agreement with some experiments. The solute
      concentration difference between the layer boundaries is assumed as constant. We
      consider two cases of horizontal external filtration flux: constant and time
      modulated. For the constant flux the system of equations that determines the
      frequency of neutral oscillations and the critical value of the Rayleigh-Darcy
      number is derived. Neutral curves of the critical parameters on the governing
      parameters are plotted. Stability maps are obtained numerically in a wide range
      of parameters of the system. We have found that taking immobilization into
      account leads to an increase in the critical value of the Rayleigh-Darcy number
      with an increase in the intensity of the external filtration flux. The case of
      weak time-dependent external flux is investigated analytically. We have shown
      that the modulated external flux leads to an increase in the critical value of
      the Rayleigh-Darcy number and a decrease in the critical wave number. For
      moderate time-dependent filtration flux the differential equation with Caputo
      fractional derivatives has been obtained for the description of the behavior near
      the convection instability threshold. This equation is analyzed numerically by
      the Floquet method; the parametric excitation of convection is observed.

PMID- 29177769
TI  - Mutual interactions between telomere heterogeneity and cell culture growth
      dynamics shape stochasticity of cell aging.
AB  - Mathematical modeling and computational simulations are often used to explain the
      stochastic nature of cell aging. The models published thus far are based on the
      molecular mechanisms of telomere biology and how they dictate the dynamics of
      cell culture proliferation. However, the influence of cell growth conditions on
      telomere dynamics has been widely overlooked. These conditions include
      interactions with surrounding cells through contact inhibition, gradual
      accumulation of non-dividing cells, culture propagation and other cell culture
      maintenance factors. In order to follow the intrinsic growth dynamics of normal
      human fibroblasts we employed the fluorescent dye DiI and FACS analysis which can
      distinguish cells that undergo different numbers of divisions within culture. We
      observed rapid generation of cell subpopulations undergoing from 0 to 9 divisions
      within growing cultures at each passage analyzed. These large differences in
      number of divisions among individual cells guarantee a strong impact on
      generation of telomere length heterogeneity in normal cell cultures and suggest
      that culture conditions should be included in future modeling of cell senescence.

PMID- 29177768
TI  - Familial Parkinson's Disease-Associated L166P Mutant DJ-1 is Cleaved by
      Mitochondrial Serine Protease Omi/HtrA2.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder.
      Mutations in the DJ-1, including L166P, are responsible for recessive early-onset
      PD. Many lines of evidence have shown that L166P is not only a loss-of-function
      mutant, but also a pro-apoptotic-like protein that results in mitochondrial
      dysfunction. L166P has been reported to be unstable and to mislocalize to
      mitochondria. However, the mechanisms underlying the instability of L166P
      compared to wild-type DJ-1 remain largely unknown. Here, we showed that
      Omi/HtrA2, a mitochondrial serine protease that has also been linked to the
      pathogenesis of PD, contributed to L166P instability. Omi directly interacted
      with and cleaved L166P in mitochondria to decrease the L166P level. However, Omi
      did not bind and cleave wild-type DJ-1. Moreover, Omi cleaved L166P at both
      serine residues 3 and 121, while L166P-induced cell death under H2O2 treatment
      was alleviated by over-expression of Omi. Our data reveal a bridge between DJ-1
      and Omi, two PD-associated genetic factors, which contributes to our
      understanding of the pathogenesis of PD.

PMID- 29177767
TI  - Membrane Aging as the Real Culprit of Alzheimer's Disease: Modification of a
      Hypothesis.
AB  - Our previous studies proposed that Alzheimer's disease (AD) is a metabolic
      disorder and hypothesized that abnormal brain glucose metabolism inducing
      multiple pathophysiological cascades contributes to AD pathogenesis. Aging is one
      of the great significant risk factors for AD. Membrane aging is first prone to
      affect the function and structure of the brain by impairing glucose metabolism.
      We presume that risk factors of AD, including genetic factors (e.g., the
      apolipoprotein E epsilon4 allele and genetic mutations) and non-genetic factors
      (such as fat, diabetes, and cardiac failure) accelerate biomembrane aging and
      lead to the onset and development of the disease. In this review, we further
      modify our previous hypothesis to demonstrate "membrane aging" as an initial
      pathogenic factor that results in functional and structural alterations of
      membranes and, consequently, glucose hypometabolism and multiple
      pathophysiological cascades.

PMID- 29177770
TI  - Interventions to Improve Medicines Management for People with Dementia: A
      Systematic Review.
AB  - BACKGROUND: The importance of optimising medicines management for people with
      dementia has been emphasised through research and policy. However, evidence is
      currently lacking regarding how to achieve this in this patient population.
      OBJECTIVE: The aim was to assess the effectiveness of medicines management
      interventions for people with dementia living in their own home or a care home,
      with or without nursing care. METHODS: A systematic literature search was
      conducted in February 2016 across six electronic databases and three trial
      registries. Inclusion criteria were randomised controlled trials of medicines
      management (prescribing, dispensing, adherence, and/or review) interventions for
      people with dementia living in their own homes or care homes, with or without
      nursing. An assessment of quality was conducted for all studies, using the
      Cochrane tool for assessing the risk of bias. All outcomes were considered using
      a narrative approach. RESULTS: Overall, 1365 articles were identified, with three
      studies eligible for inclusion (n = 475 participants). The studies were
      heterogeneous both in terms of intervention components, setting, and outcomes
      used. Aspects of medicines management targeted included medication review,
      adherence, and administration. Improvements in psychotropic prescribing were
      observed; however, the interventions had limited effects on other outcomes such
      as wellbeing, falls and dementia severity. CONCLUSION: This review highlights the
      limited number of studies examining medicines management interventions for people
      with dementia. Of the work that has been conducted to date, emphasis has been
      placed on psychotropic drug use. Future research must target community-dwelling
      dementia patients and take a holistic approach to medicines management.

PMID- 29177771
TI  - Automatic gallbladder segmentation using combined 2D and 3D shape features to
      perform volumetric analysis in native and secretin-enhanced MRCP sequences.
AB  - OBJECTIVES: We aimed to develop the first fully automated 3D gallbladder
      segmentation approach to perform volumetric analysis in volume data of magnetic
      resonance (MR) cholangiopancreatography (MRCP) sequences. Volumetric gallbladder
      analysis is performed for non-contrast-enhanced and secretin-enhanced MRCP
      sequences. MATERIALS AND METHODS: Native and secretin-enhanced MRCP volume data
      were produced with a 1.5-T MR system. Images of coronal maximum intensity
      projections (MIP) are used to automatically compute 2D characteristic shape
      features of the gallbladder in the MIP images. A gallbladder shape space is
      generated to derive 3D gallbladder shape features, which are then combined with
      2D gallbladder shape features in a support vector machine approach to detect
      gallbladder regions in MRCP volume data. A region-based level set approach is
      used for fine segmentation. Volumetric analysis is performed for both sequences
      to calculate gallbladder volume differences between both sequences. RESULTS: The
      approach presented achieves segmentation results with mean Dice coefficients of
      0.917 in non-contrast-enhanced sequences and 0.904 in secretin-enhanced
      sequences. CONCLUSION: This is the first approach developed to detect and segment
      gallbladders in MR-based volume data automatically in both sequences. It can be
      used to perform gallbladder volume determination in epidemiological studies and
      to detect abnormal gallbladder volumes or shapes. The positive volume differences
      between both sequences may indicate the quantity of the pancreatobiliary reflux.

PMID- 29177773
TI  - A useful dressing for isolated digit injuries.
AB  - We propose a useful dressing for the post-operative care of isolated digit
      injuries using Coban Self-Adherent Wrap (3M). Coban is a latex-free self-adherent
      wrap, often used for the management of lower limb wounds and venous disease. The
      benefits of this dressing include a semi-rigid support to splint the digit yet it
      is lightweight and comfortable for the patient. The memory within the material
      also allows for expansion of the dressing in response to any swelling that may
      occur in the post-operative period, with subsequent retraction of the wrap once
      this subsides. We have achieved satisfactory results through the use of Coban,
      have wrapped over 100 digits and encountered no complications.

PMID- 29177772
TI  - An 8-channel Tx/Rx dipole array combined with 16 Rx loops for high-resolution
      functional cardiac imaging at 7 T.
AB  - OBJECTIVE: To demonstrate imaging performance for cardiac MR imaging at 7 T using
      a coil array of 8 transmit/receive dipole antennas and 16 receive loops.
      MATERIALS AND METHODS: An 8-channel dipole array was extended by adding 16
      receive-only loops. Average power constraints were determined by electromagnetic
      simulations. Cine imaging was performed on eight healthy subjects. Geometrical
      factor (g-factor) maps were calculated to assess acceleration performance. Signal
      to-noise ratio (SNR)-scaled images were reconstructed for different combinations
      of receive channels, to demonstrate the SNR benefits of combining loops and
      dipoles. RESULTS: The overall image quality of the cardiac functional images was
      rated a 2.6 on a 4-point scale by two experienced radiologists. Imaging results
      at different acceleration factors demonstrate that acceleration factors up to 6
      could be obtained while keeping the average g-factor below 1.27. SNR maps
      demonstrate that combining loops and dipoles provides a more than 50% enhancement
      of the SNR in the heart, compared to a situation where only loops or dipoles are
      used. CONCLUSION: This work demonstrates the performance of a combined
      loop/dipole array for cardiac imaging at 7 T. With this array, acceleration
      factors of 6 are possible without increasing the average g-factor in the heart
      beyond 1.27. Combining loops and dipoles in receive mode enhances the SNR
      compared to receiving with loops or dipoles only.

PMID- 29177774
TI  - Surgical treatment of periprosthetic femoral fractures: a retrospective study
      with functional and radiological outcomes from 2010 to 2016.
AB  - BACKGROUND: The treatment of periprosthetic femoral fractures is a great
      challenge for the orthopedic surgeon and requires a knowledge of bone fracture
      fixation as well as skills and experience in revision surgery. The aim of this
      retrospective study was to evaluate the functional and radiological outcomes of
      periprosthetic femoral fractures surgically treated in our department from 2010
      to 2016. MATERIALS AND METHODS: This study involved 73 patients with a
      periprosthetic femoral fracture after total hip arthroplasty or hemiarthroplasty.
      Periprosthetic femoral fractures were classified using the Vancouver system.
      Functional outcomes were assessed using Harris hip score, Palmer Parker score, SF
      36 score and ambulatory status. Radiological findings were classified using Beals
      and Tower's criteria. RESULTS: The mean age of patients was 79.6 years old. Local
      risks factors were identified in 67% of the patients, principally osteoporosis
      (63.0%), followed by osteolysis (26.0%) and loosening of the stem (8.2%).
      According to the Vancouver classification, there were 10 type A, 49 type B and 14
      type C fractures. Of the type B fractures, 26 were B1, 17 were B2 and 6 were B3.
      Applying Beals and Tower's criteria, radiological results were excellent in 24
      patients (32.9%), good in 35 (47.9%) and poor in 14 (19.2%). The mean Harris hip
      score post-operatively was 72.5. CONCLUSIONS: These kinds of fractures should be
      assessed individually and the optimal treatment plan should be made in accordance
      with the bone stock quality, stem stability, location of the fracture and patient
      expectations.

PMID- 29177776
TI  - Strength and microstructure characteristics of the recycled rubber tire-sand
      mixtures as lightweight backfill.
AB  - The disposal of scrap rubber tires has induced critical environmental issue
      worldwide due to the rapid increase in the number of vehicles. Recycled scrap
      tires as a construction material in civil engineering have significant
      environmental benefits from a waste management perspective. A systematic study
      that deals with strength and microstructure characteristics of the rubber-sand
      mixtures is initiated, and mechanical response of the mixtures is discussed in
      this investigation. Experiments were conducted to evaluate the effects of rubber
      fraction on the basic properties including mass density (rho), stress-strain
      characteristics, shear strength, and unconfined compression strength (q u) of the
      rubber-sand mixtures. Additionally, scanning electron microscopy (SEM) was
      carried out to reveal the microstructure characteristics of the mixtures with
      various rubber fractions. A discussion on the micromechanics of the mixtures also
      was conducted. This study demonstrates that the rho, friction angle, and q u
      decrease linearly with an increase in rubber fraction, whereas shear strain at
      peak increases. The stress-strain characteristics of the rubber-sand mixtures
      shift from brittle to ductile as the rubber fraction increase. These changes are
      attributed to remarkably lower stiffness and higher compressibility of the rubber
      particle compared with those of the conventional mineral aggregates. With an
      increase in the rubber fraction, the mechanical response of rubber-sand mixtures
      exhibits two types: sand-like material and rubber-like material. Rubber particle
      possesses the capacity to prevent the contacted sand particles from sliding at
      lower rubber fraction, whereas it transmits the applied loadings as the rubber
      fraction increased. This outcome reinforces the practicability of using recycled
      rubber tire-sand mixtures as a lightweight backfill in subbase/base applications.

PMID- 29177775
TI  - Shortening subtrochanteric osteotomy and cup placement at true acetabulum in
      total hip arthroplasty of Crowe III-IV developmental dysplasia: results of
      midterm follow-up.
AB  - INTRODUCTION: The anatomic abnormalities in developmental dysplasia of hip (DDH)
      often make total hip replacement (THR) inevitable at a younger age. However,
      there is no universal gold standard technique of THR for high dislocated
      dysplastic hips. MATERIALS AND METHODS: Here we present the outcomes of midterm
      follow-up after THR in patients diagnosed with DDH Crowe type III and IV
      hospitalized in a tertiary center in Iran for whom placement of a cup in true
      acetabulum and selective transverse subtrochanteric osteotomy was performed. Pre-
      and postoperative Harris Hip Score, leg length discrepancy and postoperative
      complications were evaluated. RESULTS: A total of 48 patients with DDH Crowe type
      III and IV (uni- or bilateral which made 52 hips) were studied. Mean age of
      patients was 41 years with minimum follow-up ranging from 12 months to 3 years.
      Mean Harris Hip Score significantly improved from 41.70 preoperatively to 88.1 at
      last follow-up postoperatively. Leg length discrepancy of less than 2 cm was
      observed which was well tolerated using shoe lifts. Regarding postoperative
      complications, two patients had transient peroneal nerve palsy in early
      postoperative period which recovered within 2 months. No other major complication
      was encountered. CONCLUSION: THR in patients with DDH (Crowe III and IV) with a
      cup positioned in true acetabulum and transverse subtrochanteric osteotomy is a
      safe successful procedure.

PMID- 29177777
TI  - Comparative bioleaching of metals from pulverized and non-pulverized PCBs of cell
      phone charger: advantages of non-pulverized PCBs.
AB  - Sample inhomogeneity is a severe issue in printed circuit boards especially when
      we are comparing the bioleaching efficiency. To avoid the ambiguous results
      obtained due to inhomogeneity in PCBs, 12 similar cell phone chargers (of
      renowned company) having same make and batch number were collected from scrap
      market. PCBs obtained from them were used in present studies. Out of these 12,
      three PCBs were used separately for chemical analysis of PCBs with prior acid
      digestion in aqua regia. It was found that, 10.8, 68.0, and 710.9 mg/l of Zn, Pb,
      and Cu were present in it, respectively. Six PCBs were used for bioleaching
      experiment with two variations, pulverized and non-pulverized. Though the
      pulverized sample have shown better leaching than non-pulverized one, former has
      some disadvantages if overall recycling of e-waste (metallic and nonmetallic
      fraction) is to be addressed. At the end of leaching experiments, copper was
      recovered using a simple setup of electrodeposition and 92.85% recovery was
      attained. The acidophiles involved in bioleaching were identified by culture
      dependent and culture independent techniques such as DGGE and species specific
      primers in PCR.

PMID- 29177778
TI  - Development of an efficient viral aerosol collector for higher sampling flow
      rate.
AB  - Viral aerosol infection through cough generates large amounts of viral aerosol
      and can result in many adverse health effects such as influenza flu and severe
      acute respiratory syndrome (SARS). To characterize the coughed viral aerosol, the
      sampler needs to sample at higher flow rate and possess high physical collection
      efficiency as well as high viral preservation. However, most current inertia
      based high flow bioaerosol samplers are not suited for viral aerosol sampling
      since the viability will be lost doing the sampling process. Current condensation
      growth methods only have good physical collection efficiency and viral
      preservation at low flow rate (< 10 LPM). In this study, we developed a viral
      aerosol sampling system using a cooler and steam-jet aerosol collector (SJAC) for
      bioaerosol collection for the first time. The system is based on mixing
      condensation growth method and has high viral preservation at a higher flow rate
      (12.5 LPM). We control the inlet aerosol flow temperature and the SJAC mixing
      reservoir temperature to improve the physical collection efficiency and viability
      preservation of the viral aerosol. Results indicate that the physical collection
      efficiency is 70-99% for aerosol 30-100 nm when the aerosol flow and mixing
      reservoir temperature was 19 and 50  degrees C, respectively. In addition, the
      system was 7 and 22 times more efficient for viability preservation of MS2
      bacteriophage than the commonly used All Glass Impinger 30 (AGI-30) and
      BioSampler(r), respectively. Finally, the system can be applied to sample at a
      lower concentration (105 PFU/m3), and results shows the system was 4.7 times more
      efficient for viability preservation than using AGI-30 alone. The developed viral
      collection system will improve our understanding of the characteristics of
      coughed aerosol and can be used for future evaluation of respiratory protective
      equipment and environmental sampling.

PMID- 29177779
TI  - Ethanolic extract of fenugreek seeds moderates dimethoate-induced pancreatic
      damage in male rats.
AB  - Dimethoate is a widely used organophosphate insecticide known to be toxic to the
      pancreas. The aim of this study is to detect the possible protective effects of
      the fenugreek seed ethanolic extract on the biochemical, histological, and ultra
      structural abnormalities induced by dimethoate chronic exposure in the pancreas
      of adult male rats. The study was conducted on 50 adult male albino rats that
      were divided equally into 5 groups: (group I) negative control, (group II)
      vehicle control group, (group III) fenugreek-treated group that was given 400
      mg/kg ethanolic fenugreek seed extract once daily, (group IV) dimethoate group
      received 20 mg/kg/day dimethoate, and (group V) dimethoate- + fenugreek-treated
      group received a combination of dimethoate and fenugreek in the same previous
      doses. Dimethoate treatment caused a significant increase in serum glucose,
      amylase, and lipase levels and a significant decrease in serum insulin. A
      significant increase in lipid peroxidation and pro-fibrotic cytokine (TGF-beta1)
      together with a significant reduction of the antioxidant {reduced glutathione
      (GSH), catalase (CAT), superoxide dismutase (SOD)} activities and the anti
      inflammatory (IL-4) in pancreatic tissues was also recorded. There was a
      histological and ultra-structural evidence of pancreatic acinar and islet cell
      injury. The recorded abnormalities were reversed in dimethoate+fenugreek treated
      group indicating that fenugreek ethanolic extract can serve as an antidote for
      dimethoate-induced pancreatic insult.

PMID- 29177780
TI  - Performance and biofilm characteristics of biotrickling filters for ethylbenzene
      removal in the presence of saponins.
AB  - Saponins were applied to enhance ethylbenzene removal in biotrickling filters
      (BTFs), and comparison experiments were carried out to evaluate the effects of
      saponins on ethylbenzene removal and biofilm characteristics at various saponin
      concentrations. Results showed that the optimum concentration of saponins was 40
      mg/L and a maximum removal efficiency (RE) of ethylbenzene reached 84.3%. When
      the inlet ethylbenzene concentration increased, ranging from 750 to 2300 mg/m3,
      the RE decreased from 92.1 to 60.8% and from 69.4 to 44.2% for BTF1 and BTF2 in
      which saponin was and was not added, respectively. The corresponding RE declined
      from 91.1 to 40.8% and from 71.5 to 35.8% with a decreased empty bed residence
      time ranging from 45 to 7.5 s. Additionally, significant differences existed
      between both BTFs not only in the contents of polysaccharide and proteins but
      also in the surface charge of biofilms, and the ratio of protein to
      polysaccharide increased with the increase of saponin concentration, which
      indicated the presumable effect of saponins on liquid-biofilm transfer rates of
      ethylbenzene. Mechanisms for the enhanced removal of hydrophobic volatile organic
      compounds at the presence of surfactants were also discussed.

PMID- 29177781
TI  - Bioaccumulation of selected heavy metals and histopathological and
      hematobiochemical alterations in backyard chickens reared in an industrial area,
      India.
AB  - This study was carried out to determine the concentrations of four heavy metals,
      cadmium (Cd), lead (Pb), copper (Cu), and cobalt (Co), and histopathological
      lesions in tissues of chickens reared in an industrial area of West Bengal,
      India. In particular, Mejhia Block was selected as a heavy metal-exposed area and
      Vatar Block (120 km away from industrially polluted areas) as a reference site.
      Samples were collected from the backyard chickens in these areas. Concentrations
      of heavy metals in soil, water, feedstuffs, tissues (liver, kidney, spleen, lung,
      and muscle), and droppings were greater (p < 0.05) in the polluted site than in
      the reference site. The greatest tissue concentrations of Cd and Pb were noted in
      the kidney, followed by the liver, lung, spleen, and muscle, whereas Cu and Co
      concentrations accumulated in these tissues resulted in the following: liver >
      kidney > lung > spleen > muscle. Heavy metal concentrations were greater in older
      chickens (> 1 year) than in young chickens (< 1 year). Packed cell volume, total
      erythrocyte counts, hemoglobin, total protein, and total leucocyte counts were
      significantly (p < 0.01) lower in the blood picture of chickens in the exposed
      area. Different serum enzymes and biochemical profiles were altered due to heavy
      metal exposure. Histological changes revealed necrotic lesions and tubulitis in
      the kidney, degeneration and necrosis in liver parenchyma, and periarteriolitis,
      peribronchiolitis, and presence of hemosiderin pigment in the lung of chickens in
      the exposed site. Results indicated that backyard chickens in heavy metal-exposed
      site may show pathological lesions in different tissues due to accumulation of
      heavy metals, and thus, the consumption of chicken meat from the industrially
      exposed site may pose a potential health risk to local residents of polluted
      sites.

PMID- 29177782
TI  - Residues and health risk assessment of typical antibiotics in aquatic products
      from the Dongting Lake, China-"Did you eat "Antibiotics" today?"
AB  - The contamination level of 12 antibiotics in 8 species of fish and shrimp from
      the Dongting Lake, China, was firstly studied. In total, the concentrations of
      antibiotics in fish and shrimp were lower, which were far lower than the maximum
      residue limits. The most abundant compound was enrofloxacin followed by
      sulfadiazine, sulfamethoxazole, sarafloxacin, and sulfadimidine with the highest
      content from 0.37 to 1.06 ng g-1. The concentrations in Silurus asotus, Cyprinus
      carpio, and Palinuridae were higher. Concentrations in fish and shrimp from
      different water layers showed spatial difference, with the order of benthos and
      middle-lower species > middle-upper species. In addition, the antibiotic content
      could be affected by the diet, which showed the concentration level of
      antibiotics decreased in the order of carnivorous > omnivorous > phytophagous
      species. Human health risk assessment based on potential fish consumption
      indicates that main antibiotic risk factors were enrofloxacin and sarafloxacin,
      and main risk species were Silurus asotus and Palinuridae. The daily risk
      quotient of these antibiotics to rural residents was lower than townsmen. This
      study is the first report of antibiotic content in fish and shrimp from the
      Dongting Lake, which could enrich the research of emerging pollutants in aquatic
      products.

PMID- 29177783
TI  - Modification of chitosan/calcium alginate/Fe3O4 hydrogel microsphere for
      enhancement of Cu(II) adsorption.
AB  - Copper in drinking water causes a significant environmental problem. Composite
      material based on alginate hydrogel has been gaining attention in the field of
      Cu(II) adsorption. However, alginate-based hydrogel exhibits poor mechanical
      property and relative low adsorption capacity which limit their application. The
      present study is devoted to the modification of chitosan/calcium alginate/Fe3O4
      (CAF) hydrogel microsphere by NaOH solution for enhancement of Cu(II) adsorption.
      Results reveal that modification of CAF via NaOH solution significantly improves
      the mechanical strength and Cu2+ adsorption capacity of pristine materials. FTIR
      and XRD analysis confirms that CAF and newly prepared materials (NACAF) are
      successfully prepared. SEM and EDX are employed to analyze the surface morphology
      and elemental composition, respectively, both before and after their loading with
      Cu2+. XPS study demonstrates adsorption mechanism is based on chelation and ion
      exchange. Compressive stress-strain curves demonstrate NACAF has better
      mechanical performance than CAF. The adsorption kinetics of the two adsorbents
      follow a pseudo-second-order model. The equilibrium data were best described by
      Langmuir isotherm model, and the estimated maximum equilibrium sorption capacity,
      q m,is 261.31 mg/g for the NACAF, which is larger than that of CAF (145.39 mg/g).
      Hence, NACAF shows excellent mechanical strength and high sorption capacity for
      Cu2+. It has great potential for Cu(II) removal in aqueous solutions.

PMID- 29177784
TI  - How tapeworm infection and consumption of a Cd and Zn hyperaccumulating plant may
      affect Cu, Fe, and Mn concentrations in an animal-a plant consumer and tapeworm
      host.
AB  - This study evaluated the effects of a hyperaccumulator plant (Arabidopsis
      halleri), containing surplus of cadmium (Cd) and zinc (Zn) and being an admixture
      to the rat feed, on concentrations of copper (Cu), iron (Fe), and manganese (Mn)
      in the tissues of experimental rats infected/uninfected with the tapeworm
      (Hymenolepis diminuta). Male Wistar rats were divided into three groups (00, P0,
      and PT); the P0 and PT animals were fed a standard mixture for rats (ST-1)
      supplemented with the plant A. halleri at a weekly Zn and Cd dosage of 123 and 1
      mg, respectively. Moreover, rats from the group PT were infected with the
      tapeworm. The group 00 served as control animals fed only ST-1 having no tapeworm
      infection. Rats were euthanized after 6 weeks, and Cu, Fe, and Mn levels were
      determined in rat and tapeworm tissues. The results indicated that both the
      consumption of hyperaccumulator plant and/or presence of tapeworms did have
      significant effect on Cu, Fe, and Mn concentrations in the host tissues.
      Concentrations of all the elements were higher in the rat liver and partially
      kidneys than in the tapeworms, and the concentrations of Cu, Fe, and Mn were
      affected by the consumption of Cd/Zn hyperaccumulator plants. Particularly, Fe
      concentrations in all rat tissues were significantly increased by consumption of
      A. halleri while decreased by the presence of tapeworms. Overall, the consumption
      of a Cd/Zn hyperaccumulator plant and tapeworm infection cause an imbalance in
      Cu, Fe, and Mn concentrations in the tissues of a consumer (experimental rats).

PMID- 29177786
TI  - Nematicidal potential and specific enzyme activity enhancement potential of neem
      (Azadirachta indica A. Juss.) aerial parts.
AB  - Nematodes are considered as major plant parasites damaging most of the crops, and
      neem plant exhibits potential nematicidal and insecticidal properties. This study
      aimed to check nemato-toxic potential of neem (Azadirachta indica) plant using in
      vitro and in-planta trials against Meloidogyne incognita. The findings suggested
      that the neem extracts were lethal to second-stage juvenile (J2) and egg hatching
      with simultaneous enhancement in treated tomato plant growth. The egg numbers of
      M. incognita found less sensitive to the aqueous and alcoholic extracts than
      those of J2 as per LC50 values. Complete mortality of J2s was recorded at 40, 60,
      and 80% of neem standard extract (SE) dilutions and for undiluted SE of neem. The
      undiluted SE extract showed 100% inhibition of egg production. The highest
      reductions in the number of galls/root system, J2 population, and egg production
      were observed with 80, 85, and 82% SE as compared control (untreated distilled
      water). The maximum 250% growth increment was observed in the length of tomato
      roots supplemented with neem extracts. Resistance-related enzyme [phenylalanine
      ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POX)] activities
      in tomato plant have been increased significantly by supplementation with neem
      extracts. It appears that the aerial parts of neem (A. indica) extracts showed
      significant and sustainable eco-friendly nemato-toxic potential towards M.
      incognita growth inhibition and eradication using alcoholic extracts compared to
      aqueous. From this study, it was concluded that the neem aerial parts were useful
      for the control of M. incognita and could be a possible replacement for synthetic
      nematicides in crop protection with utilization in enhancement of specific enzyme
      activity in tomato plants.

PMID- 29177785
TI  - Elemental composition of PM2.5 in the urban environment of San Juan, Argentina.
AB  - This study contributes to the current knowledge about air pollution in the
      province of San Juan, Argentina. Sampling was carried out to measure the fine
      particulate matter in the atmosphere (PM2.5) of the city of San Juan. PM2.5 was
      collected continuously during the winter and spring seasons of 2014 and 2015, and
      the concentrations of 14 elements (Pb, Ca, K, Cd, Ni, Cr, Mn, V, Cu, Ti, Ba, Co,
      Sr, and Fe) were determined in PM2.5 filters using the technique of X-ray
      fluorescence by synchrotron radiation (SR-XRF). The results revealed that PM2.5
      presented annual and seasonal variations, showing a higher concentration during
      the winter seasons. In addition, for the elements quantified in the filters, a
      multivariate analysis (Positive Matrix Factorization) was performed to identify
      the main sources of emission of these elements in the study area, with a series
      of components being obtained that corresponded to their compositions, which were
      assigned physical meanings. The first factor, which was the most important in
      contribution of the sum of the measured elements (45%), was determined mainly by
      the elements K, Ti, V, Mn, and Fe, which came predominantly from soil particles.
      The second factor contributed 30% to the measured species in PM2.5, with higher
      Ba and Zn content perhaps being related to emissions from vehicular traffic.
      Finally, the third factor, in which Pb, Cr, and Ca predominated, may be an
      indicator of industrial activity and contributed 25% of the sum of the measured
      elements of PM2.5. The results of this study provide the first PM composition
      database in the province, and this can now be used in the development of
      mitigation and prevention programs.

PMID- 29177787
TI  - Trace metal accumulation by Ranunculus sceleratus: implications for
      phytostabilization.
AB  - This study investigated the growth response of Ranunculus sceleratus to pollution
      and its capacity to accumulate trace metals for its use as a phytoremediator in
      Lake Maruit, Egypt. Three basins (main basin, fish farm, and southwestern basin)
      representing the natural distribution of the plant as well as the pollution loads
      in the lake, were chosen for collecting plant and sediment samples. In each basin
      ten quadrats (0.5 m * 0.5 m), distributed equally along two sites, were selected
      for measuring growth parameters, nutrients, and trace metal concentration. The
      highest biomass of the shoot and root (610 and 236 g m-2) was recorded in the
      main basin and fish farm, respectively. R. sceleratus accumulated high
      concentrations of Cu and Pb (27.7 and 9.9 mg kg-1), while toxic concentration of
      Mn (2508.0 mg kg-1) in their roots compared to shoots. The bioaccumulation factor
      (BF) for the investigated metals was greater than one, and in the decreasing
      order: Ni (27.1) > Zn (20.0) > Cd (16.4) > Cu (7.7) > Mn (3.9) > Pb (3.6). The
      translocation factor of all analyzed trace metals was less than one. The ability
      of R. sceleratus to accumulate Mn, Ni, Cu, and Pb in its roots indicates the
      potential use of this species for phytostabilization of these metals (mainly Mn)
      in contaminated water bodies.

PMID- 29177788
TI  - Editorial over the Many Faces of Vitamin D in Chronic Kidney Disease: from
      Mineral to Immune-Inflammatory Modulator.

PMID- 29177789
TI  - Carotid near-occlusion frequently has high peak systolic velocity on Doppler
      ultrasound.
AB  - PURPOSE: Carotid near-occlusion is a tight atherosclerotic stenosis of the
      internal carotid artery (ICA) resulting in decrease in diameter of the vessel
      lumen distal to the stenosis. Near-occlusions can be classified as with or
      without full collapse, and may have high peak systolic velocity (PSV) across the
      stenosis, mimicking conventional > 50% carotid artery stenosis. We aimed to
      determine how frequently near-occlusions have high PSV in the stenosis and
      determine how accurately carotid Doppler ultrasound can distinguish high-velocity
      near-occlusion from conventional stenosis. METHODS: Included patients had near
      occlusion or conventional stenosis with carotid ultrasound and CT angiogram (CTA)
      performed within 30 days of each other. CTA examinations were analyzed by two
      blinded expert readers. Velocities in the internal and common carotid arteries
      were recorded. Mean velocity, pulsatility index, and ratios were calculated,
      giving 12 Doppler parameters for analysis. RESULTS: Of 136 patients, 82 had
      conventional stenosis and 54 had near-occlusion on CTA. Of near-occlusions, 40
      (74%) had high PSV (>= 125 cm/s) across the stenosis. Ten Doppler parameters
      significantly differed between conventional stenosis and high-velocity near
      occlusion groups. However, no parameter was highly sensitive and specific to
      separate the groups. CONCLUSION: Near-occlusions frequently have high PSV across
      the stenosis, particularly those without full collapse. Carotid Doppler
      ultrasound does not seem able to distinguish conventional stenosis from high
      velocity near-occlusion. These findings question the use of ultrasound alone for
      preoperative imaging evaluation.

PMID- 29177790
TI  - Computational Intelligence for Medical Imaging Simulations.
AB  - This paper describes how to simulate medical imaging by computational
      intelligence to explore areas that cannot be easily achieved by traditional ways,
      including genes and proteins simulations related to cancer development and
      immunity. This paper has presented simulations and virtual inspections of BIRC3,
      BIRC6, CCL4, KLKB1 and CYP2A6 with their outputs and explanations, as well as
      brain segment intensity due to dancing. Our proposed MapReduce framework with the
      fusion algorithm can simulate medical imaging. The concept is very similar to the
      digital surface theories to simulate how biological units can get together to
      form bigger units, until the formation of the entire unit of biological subject.
      The M-Fusion and M-Update function by the fusion algorithm can achieve a good
      performance evaluation which can process and visualize up to 40 GB of data within
      600 s. We conclude that computational intelligence can provide effective and
      efficient healthcare research offered by simulations and visualization.

PMID- 29177791
TI  - SR 11302, an AP-1 Inhibitor, Reduces Metastatic Lesion Formation in Ex Vivo 4D
      Lung Cancer Model.
AB  - Activator protein (AP) -1 is a transcription factor, plays important role in cell
      differentiation, proliferation and apoptosis. Analysis of tumor cells grown on ex
      vivo 4D lung cancer model shows increase in components of AP-1, c-Fos and c-Jun
      in circulating tumor cells (CTC) compared to primary tumor. Our aim was to
      determine whether the AP-1 inhibitor SR11302 reduces metastatic lesion formation
      in the 4D model. Human lung cancer cell lines A549, H1299, and H460 were grown in
      the 4D model and treated with SR11302 (1 MUM). We compared the number of cells in
      the metastatic site upon SR11302 treatment and number of viable CTCs isolated
      from the 4D model with parental cells treated/untreated with SR11302 on a petri
      dish. There were significantly fewer tumor cells per high-power field on
      metastatic site in 4D model seeded with H460 (p = 0.009), A549 (p = 0.01), or
      H1299 (p = 0.02) cells treated with SR11302. Furthermore, the CTCs from SR11302
      treated 4D models, seeded with H460 (p = 0.04), A549 (p = 0.008), or H1299 (p =
      0.01) cells had significantly fewer viable tumor cells after 4 days in culture
      than the respective untreated control. However, the SR11302 had no impact on the
      viability of parental H460 (p = 0.87), A549 (p = 0.93), or H1299 (p = 0.25) cells
      grown on a petri dish (2D). SR11302 reduces metastatic lesion formation in the ex
      vivo 4D lung cancer model due to the presence of an independent yet common
      pathway among three cell lines. The ex vivo 4D model may provide a tool to better
      understand the complex process of metastasis.

PMID- 29177792
TI  - New 8,12;8,20-diepoxy-8,14-secopregnane hexa- and hepta-glycosides from the roots
      of Asclepias tuberosa.
AB  - Previously, phytochemical investigation of the roots of Asclepias tuberosa
      (Asclepiadaceae) led to the isolation of some 8,12;8,20-diepoxy-8,14-secopregnane
      tri-, tetra-, and penta-glycosides. An additional eight new minor 8,12;8,20
      diepoxy-8,14-secopregnane glycosides were afforded in the recent investigation of
      this plant. These glycosides consisted of six or seven 2,6-dideoxy-hexopyranoses
      together with the aglycone, tuberogenin. The structures of each of these
      compounds were established using NMR, mass spectroscopic analysis and chemical
      evidence. As 8,12;8,20-diepoxy-8,14-secopregnane-type glycosides were observed
      only in A. tuberosa, these compounds were considered to be characteristic
      phytochemicals of this plant.

PMID- 29177793
TI  - Steroid-induced hyperglycemic chorea in a patient without diabetes mellitus.

PMID- 29177794
TI  - Imaging of the thymus in myotonic dystrophy type 1.
AB  - The occurrence of thymoma in myotonic dystrophy type 1 (DM1) has been
      occasionally reported, and an increased risk of tumors has been observed. We
      performed imaging of the thymus in 22 patients carrying DMPK expansion. Clinical
      examination and routine instrumental exams were performed at the same time. We
      observed no thymic abnormalities in 13 subjects, thymic hyperplasia in eight
      patients, and an invasive thymoma in one case. Subjects with thymic abnormalities
      did not show peculiarities as regards clinical and electrophysiological features.
      We observed thymoma in one patient with an expansion in the higher range.
      Abnormalities of the thymus including hyperplasia and thymoma can be present in
      DM1, but do not seem to play a major role in DM1 pathogenesis. Further studies
      are needed to understand if some RNA splicing factors involved in DM1 and
      influenced by CTG expansion size could have a role in thymocytes proliferation.

PMID- 29177795
TI  - Myocardial injury after endovascular revascularization in critical limb ischemia
      predicts 1-year mortality: a prospective observational cohort study.
AB  - BACKGROUND: Patients with critical limb ischemia (CLI) are at increased risk of
      cardiovascular complications and mortality. To determine (1) incidence of
      myocardial injury following endovascular revascularization, and (2) relationship
      between myocardial injury with 1-year mortality and major adverse cardiovascular
      events (MACE; i.e., composite of myocardial infarction, stroke, and death).
      METHODS AND RESULTS: Single-center, prospective cohort study of CLI patients >=
      45 years of age, who underwent endovascular revascularization with overnight
      hospitalization. High-sensitive troponins T (hsTnTs) were measured on admission,
      3-6 h after endovascular revascularization and the subsequent morning. Myocardial
      injury after endovascular revascularization was defined as an hsTnT >= 14 ng/L
      with a relative increase >= 30% from the baseline value. We also evaluated other
      myocardial injury hsTnT thresholds (i.e., >= 30, >= 40, >= 60, and >= 80 ng/L).
      239 consecutive patients (56% male, mean age 71.5 +/- 10.1 years) were included;
      one patient was lost to follow-up. At 1 year, there were 34 deaths (14.2%), and
      48 MACE (20.5%). Myocardial injury with the hsTnT threshold of 14 ng/L and
      relative increase by >= 30% from the baseline level occurred in 61 patients
      (25.5%). Myocardial injury was independently associated with 1-year mortality
      ([aHR], 2.44; 95% CI 1.18-5.06, for hsTnT >= 14 ng/L to aHR, 3.34; 95% CI 1.29
      8.65 for hsTnT >= 80 ng/L). Myocardial injury was also independently associated
      with 1-year MACE ([AOR] 2.89; 95% CI 1.41-5.92 for hsTnT >= 14 ng/L to AOR, 6.69;
      95% CI 2.17-20.68 for hsTnT >= 80 ng/L). 85.2% patients who had myocardial injury
      did not have ischemic clinical symptoms or electrocardiography changes. In
      sensitive analysis with exclusion of symptomatic patients that developed
      myocardial injury for the hsTnT >= 14 ng/L threshold, both the 1-year mortality
      (aHR: 2.19; CI 1.02-4.68; p = 0.04), and 1-year MACE (OR 2.25; CI 1.06-4.77; p =
      0.036) remained significant. CONCLUSIONS: Myocardial injury is common following
      endovascular revascularization for CLI and associated with the risk of 1-year
      mortality and MACE.

PMID- 29177796
TI  - Molecular and Cellular Mechanisms Involved in Mesenchymal Stem Cell-Based Therapy
      of Inflammatory Bowel Diseases.
AB  - Mesenchymal stem cells (MSCs) are promising resource for the therapy of
      inflammatory bowel diseases (IBDs) on the grounds of their differentiation
      capabilities and immuno-modulatory characteristics. Results of clinical studies
      indicate that local application of MSCs is a secure and beneficial approach for
      the treatment of perianal fistulas while systemic application of MSCs leads to
      the attenuation or aggravation of IBDs. Herein, we emphasized molecular
      mechanisms and approaches that should improve efficacy of MSC-based therapy of
      IBDs.

PMID- 29177797
TI  - A Systematic Review Comparing the Acceptability, Validity and Concordance of
      Discrete Choice Experiments and Best-Worst Scaling for Eliciting Preferences in
      Healthcare.
AB  - OBJECTIVE: The aim of this study was to compare the acceptability, validity and
      concordance of discrete choice experiment (DCE) and best-worst scaling (BWS)
      stated preference approaches in health. METHODS: A systematic search of EMBASE,
      Medline, AMED, PubMed, CINAHL, Cochrane Library and EconLit databases was
      undertaken in October to December 2016 without date restriction. Studies were
      included if they were published in English, presented empirical data related to
      the administration or findings of traditional format DCE and object-, profile- or
      multiprofile-case BWS, and were related to health. Study quality was assessed
      using the PREFS checklist. RESULTS: Fourteen articles describing 12 studies were
      included, comparing DCE with profile-case BWS (9 studies), DCE and multiprofile
      case BWS (1 study), and profile- and multiprofile-case BWS (2 studies). Although
      limited and inconsistent, the balance of evidence suggests that preferences
      derived from DCE and profile-case BWS may not be concordant, regardless of the
      decision context. Preferences estimated from DCE and multiprofile-case BWS may be
      concordant (single study). Profile- and multiprofile-case BWS appear more
      statistically efficient than DCE, but no evidence is available to suggest they
      have a greater response efficiency. Little evidence suggests superior validity
      for one format over another. Participant acceptability may favour DCE, which had
      a lower self-reported task difficulty and was preferred over profile-case BWS in
      a priority setting but not necessarily in other decision contexts. CONCLUSION:
      DCE and profile-case BWS may be of equal validity but give different preference
      estimates regardless of the health context; thus, they may be measuring different
      constructs. Therefore, choice between methods is likely to be based on normative
      considerations related to coherence with theoretical frameworks and on pragmatic
      considerations related to ease of data collection.

PMID- 29177798
TI  - Predicting the risk of cucurbit downy mildew in the eastern United States using
      an integrated aerobiological model.
AB  - Cucurbit downy mildew caused by the obligate oomycete, Pseudoperonospora
      cubensis, is considered one of the most economically important diseases of
      cucurbits worldwide. In the continental United States, the pathogen overwinters
      in southern Florida and along the coast of the Gulf of Mexico. Outbreaks of the
      disease in northern states occur annually via long-distance aerial transport of
      sporangia from infected source fields. An integrated aerobiological modeling
      system has been developed to predict the risk of disease occurrence and to
      facilitate timely use of fungicides for disease management. The forecasting
      system, which combines information on known inoculum sources, long-distance
      atmospheric spore transport and spore deposition modules, was tested to determine
      its accuracy in predicting risk of disease outbreak. Rainwater samples at disease
      monitoring sites in Alabama, Georgia, Louisiana, New York, North Carolina, Ohio,
      Pennsylvania and South Carolina were collected weekly from planting to the first
      appearance of symptoms at the field sites during the 2013, 2014, and 2015 growing
      seasons. A conventional PCR assay with primers specific to P. cubensis was used
      to detect the presence of sporangia in rain water samples. Disease forecasts were
      monitored and recorded for each site after each rain event until initial disease
      symptoms appeared. The pathogen was detected in 38 of the 187 rainwater samples
      collected during the study period. The forecasting system correctly predicted the
      risk of disease outbreak based on the presence of sporangia or appearance of
      initial disease symptoms with an overall accuracy rate of 66 and 75%,
      respectively. In addition, the probability that the forecasting system correctly
      classified the presence or absence of disease was >= 73%. The true skill
      statistic calculated based on the appearance of disease symptoms in cucurbit
      field plantings ranged from 0.42 to 0.58, indicating that the disease forecasting
      system had an acceptable to good performance in predicting the risk of cucurbit
      downy mildew outbreak in the eastern United States.

PMID- 29177799
TI  - [Behavior disorders in dementia: demands for personnel adaptation are more than
      justified].

PMID- 29177800
TI  - [Neurointensive care medicine-from where, where to?]

PMID- 29177801
TI  - Methodological Challenges to the Evaluation of Interventions for Foster/Kinship
      Carers and Children: A Systematic Review.
AB  - Caregivers of children in alternative care face a complex range of challenges
      that can result in placement disruption and poor long-term outcomes.
      Interventions designed to help carers meet these challenges report positive
      outcomes. Nevertheless, several reviewers have reported these positive results
      may be mitigated by limitations in trial methodology. This review aims to
      systematically review these methodological challenges and limitations, to provide
      an analysis of the current state of the evidence base for these interventions. A
      systematic review was conducted into the methods used to evaluate the
      effectiveness of psychosocial interventions for foster and kinship carers.
      Limitations relating to internal validity, external validity and clinical
      heterogeneity were identified and synthesised. Seventeen studies met inclusion
      criteria. The quality of methods used in the included studies is mixed, with high
      and unknown levels of bias in the majority of trials. Heterogeneity in
      participant characteristics, intervention aims and outcome measures across
      interventions reflect the diversity of carer and child needs and make it
      difficult to generalise results or compare and synthesise the efficacy of
      different interventions. These factors limit the application of trial results to
      evidence-based clinical practice. The diverse and complex needs of this
      population present significant challenges to robustly evaluating interventions
      for foster/kinship families. Participant needs, theoretical approaches,
      intervention aims and outcome measures need to be better coordinated, both within
      trials and across the field. Exploratory research should be used to generate
      focussed and concrete hypotheses that can be robustly tested in high-quality
      randomised controlled trials. Protocol registration number: CRD 42017048415.

PMID- 29177802
TI  - Correction to: Certolizumab Pegol in the Treatment of Psoriasis and Psoriatic
      Arthritis: Preliminary Real-Life Data.
AB  - In the original publication, part Fig. 3b and c were interchanged. The correct
      versions are given below.

PMID- 29177803
TI  - Cytotoxic and antimicrobial effects of biosynthesized ZnO nanoparticles using of
      Chelidonium majus extract.
AB  - The basic goal of this study was to synthesize zinc oxide nanoparticles using the
      Chelidonium majus extract and asses their cytotoxic and antimicrobial properties.
      The synthesized ZnO NPs were characterized by UV-Vis, Scanning Electron
      Microscopy (SEM) with EDS profile, Fourier Transform Infrared Spectroscopy
      (FTIR), X-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and
      Atomic Force Microscopy (AFM). The aforementioned methods confirmed that the size
      of synthesized ZnO nanoparticles was at the range of 10 nm. The antimicrobial
      activity of ZnO nanoparticles synthesized using the Ch. majus extract was tested
      against standard strains of bacteria (Staphylococcus aureus NCTC 4163,
      Pseudomonas aeruginosa NCTC 6749, Escherichia coli ATCC 25922), yeast (Candida
      albicans ATCC 10231), filamentous fungi (molds: Aspergillus niger ATCC 16404,
      dermatophytes: Trichophyton rubrum ATCC 28188), clinical strains of bacteria
      (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus) and yeast
      (Candida albicans). The study showed that zinc oxide nanoparticles were excellent
      antimicrobial agents. What is more, biologically synthesized ZnO nanoparticles
      demonstrate high efficiency in treatment of human non-small cell lung cancer
      A549.

PMID- 29177804
TI  - MRI of the sacroiliac joints in spondyloarthritis: the added value of intra
      articular signal changes for a 'positive MRI'.
AB  - OBJECTIVE: To determine if intra-articular signal changes at the sacroiliac joint
      space on MRI have added diagnostic value for spondyloarthritis, when compared to
      bone marrow edema (BME). MATERIALS AND METHODS: A retrospective study was
      performed on the MRIs of sacroiliac joints of 363 patients, aged 16-45 years,
      clinically suspected of sacroiliitis. BME of the sacroiliac joints was correlated
      to intra-articular sacroiliac joint MR signal changes: high T1 signal, fluid
      signal, ankylosis and vacuum phenomenon (VP). These MRI findings were correlated
      with final clinical diagnosis. Sensitivity (SN), specificity (SP), likelihood
      ratios (LR), predictive values and post-test probabilities were calculated.
      RESULTS: BME had SN of 68.9%, SP of 74.0% and LR+ of 2.6 for diagnosis of
      spondyloarthritis. BME in absence of intra-articular signal changes had a lower
      SN and LR+ for spondyloarthritis (SN = 20.5%, LR+ 1.4). Concomitant BME and high
      T1 signal (SP = 97.2%, LR + = 10.5), BME and fluid signal (SP = 98.6%, LR + =
      10.3) or BME and ankylosis (SP = 100%) had higher SP and LR+ for
      spondyloarthritis. Concomitant BME and VP had low LR+ for spondyloarthritis (SP =
      91%, LR + =0.9). When BME was absent, intra-articular signal changes were less
      prevalent, but remained highly specific for spondyloarthritis. CONCLUSION: Our
      results suggest that both periarticular and intra-articular MR signal of the
      sacroiliac joint should be examined to determine whether an MRI is 'positive' or
      'not positive' for sacroiliitis associated with spondyloarthritis.

PMID- 29177805
TI  - Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly
      Isolated Mouse Dorsal Root Ganglion Neurons.
AB  - Voltage-gated potassium (KV) currents, subdivided into rapidly inactivating A
      type currents (I A) and slowly inactivating delayed rectifier currents (I K),
      play a fundamental role in modulating pain by controlling neuronal excitability.
      The effects of Honokiol (Hon), a natural biphenolic compound derived from
      Magnolia officinalis, on KV currents were investigated in freshly isolated mouse
      dorsal root ganglion neurons using the whole-cell patch clamp technique. Results
      showed that Hon inhibited I A and I K in concentration-dependent manner. The IC50
      values for block of I A and I K were 30.5 and 25.7 uM, respectively. Hon (30 uM)
      shifted the steady-state activation curves of I A and I K to positive potentials
      by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state
      of I A were unaffected. These results suggest that Hon preferentially interacts
      with the active states of the I A and I K channels, and has no effect on the
      resting state and inactivated state of the I A channel. Blockade on K+ channels
      by Hon may contribute to its antinociceptive effect, especially anti-inflammatory
      pain.

PMID- 29177806
TI  - The long-term survival in primary retroperitoneal mucinous cystadenocarcinoma: a
      case report.
AB  - BACKGROUND: Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is
      extremely rare, and its biological behavior, pathogenesis, optimum treatments,
      and prognosis remain to be elucidated. We herein report a case of PRMC with an 80
      month follow-up. CASE PRESENTATION: A 29-year-old woman was diagnosed with
      unknown retroperitoneal tumor with benign right ovarian cyst and uterine
      fibroids, and she underwent laparotomy. The tumor was completely resected with a
      subsequent histopathological diagnosis of primary retroperitoneal mucinous
      cystadenocarcinoma (PRMC). Eighty months after surgery, she remains recurrence
      free. CONCLUSION: PRMC is an extremely rare tumor. Only around 60 cases have so
      far been published in the literature. The preoperative diagnosis of PRMC is
      difficult, and a definitive diagnosis can usually only be made based on the
      findings of histopathological examinations after surgery. Presently, only radical
      resection is useful for both diagnostic and therapeutic purposes. The optimal
      long-term management after surgery is still not well established. Further studies
      on PRMC are therefore needed to elucidate the etiology and establish effective
      treatments.

PMID- 29177807
TI  - Collagen degradation as a possibility to determine the post-mortem interval (PMI)
      of animal bones: a validation study referring to an original study of Boaks et
      al. (2014).
AB  - Estimation of the post-mortem interval (PMI) of unknown skeletal remains is a
      common forensic task. Boaks and colleagues demonstrated a new method for PMI
      estimation in showing a reduction of the collagen to non-collagen content (Co/NCo
      ratio) in porcine bones after a PMI of 12 months using the Sirius Red/Fast Green
      Collagen Staining Kit from Chondrex in 2014 (Boaks et al. Forensic Sci Int 240:
      104-110, 2014). The aim of our study was to reproduce this method and to
      investigate if the method could be used for forensic issues. Sixteen fresh
      porcine bones were placed in prepared boxes where they were treated regularly
      with distilled water or with water from hay infusions. For determining the Co/NCo
      ratio, we used the Sirius Red/Fast Green Collagen Staining Kit from Chondrex,
      which stains collagenous (Co) proteins red and non-collagenous (NCo) proteins
      green Chondrex Inc. (2008). After a PMI of 1-3 months, an analysis of porcine
      bone thin sections was performed on the one hand with spectrophotometry, on the
      other hand with stereomicroscopy. Using spectrophotometry, we go low and
      partially negative Co/NCo ratios which were up to 100-fold lower than the results
      we expected to get. The data we got by stereomicroscopy and calculating the
      Co/NCo ratio from extracting the red and green content with the software MATLAB
      and so calculating the Co/NCo ratio showed a correlation between PMI and the
      Co/NCo ratio in the porcine bone samples. Regular addition of distilled water or
      water from a hay infusion did not produce any significant differences so that an
      increased presence of microorganisms had obviously no influence on collagen
      degradation.

PMID- 29177810
TI  - Highlight report: physiologically-based modeling of diseased liver tissue.

PMID- 29177808
TI  - The prone sleeping position and SIDS. Historical aspects and possible
      pathomechanisms.
AB  - The incidence of SIDS decreased during the previous 25 years significantly. This
      is mainly due to epidemiological research identifying important risk factors such
      as prone sleeping position and subsequent campaigns to reduce this risk
      factor.Originally, the prone sleeping position for babies had been strongly
      recommended in the sixties and seventies despite previous publications pointed to
      the associated risk. Worldwide, many infants died of SIDS whose deaths could have
      been avoided. Today, the recommendation that infants should sleep in supine
      position has been scientifically verified. In supine sleeping position,
      pathophysiological mechanisms can be avoided which may lead to hypoxia and death
      in prone position. Such mechanisms could be occlusion of airways (in particularly
      associated with face-down position), elevated diaphragm, positional cerebral
      hypoxia caused by constriction of arteries, rebreathing CO2, and
      overheating.Irrespective of the specific pathomechanism leading to death in
      individual cases, it has been established that the prone position is the most
      important risk factor for SIDS and therefore should be incorporated in the
      definition of the term SIDS.

PMID- 29177809
TI  - Parallel in vivo and in vitro transcriptomics analysis reveals calcium and zinc
      signalling in the brain as sensitive targets of HBCD neurotoxicity.
AB  - Hexabromocyclododecane (HBCD) is a brominated flame retardant (BFR) that
      accumulates in humans and affects the nervous system. To elucidate the mechanisms
      of HBCD neurotoxicity, we used transcriptomic profiling in brains of female mice
      exposed through their diet to HBCD (199 mg/kg body weight per day) for 28 days
      and compared with those of neuronal N2A and NSC-19 cell lines exposed to 1 or 2
      uM HBCD. Similar pathways and functions were affected both in vivo and in vitro,
      including Ca2+ and Zn2+ signalling, glutamatergic neuron activity, apoptosis, and
      oxidative stress. Release of cytosolic free Zn2+ by HBCD was confirmed in N2A
      cells. This Zn2+ release was partially quenched by the antioxidant N-acetyl
      cysteine indicating that, in accordance with transcriptomic analysis, free
      radical formation is involved in HBCD toxicity. To investigate the effects of
      HBCD in excitable cells, we isolated mouse hippocampal neurons and monitored Ca2+
      signalling triggered by extracellular glutamate or zinc, which are co-released
      pre-synaptically to trigger postsynaptic signalling. In control cells application
      of zinc or glutamate triggered a rapid rise of intracellular [Ca2+]. Treatment of
      the cultures with 1 uM of HBCD was sufficient to reduce the glutamate-dependent
      Ca2+ signal by 50%. The effect of HBCD on zinc-dependent Ca2+ signalling was even
      more pronounced, resulting in the reduction of the Ca2+ signal with 86%
      inhibition at 1 uM HBCD. Our results show that low concentrations of HBCD affect
      neural signalling in mouse brain acting through dysregulation of Ca2+ and Zn2+
      homeostasis.

PMID- 29177811
TI  - Genetic and Syndromic Causes of Obesity and its Management.
AB  - The aim of this article is to provide an in depth review of the rare genetic and
      syndromic forms of childhood obesity. The authors demonstrate the complexity and
      inter-relationships of the leptin-melanocortin signaling pathway and its central
      nervous system and systemic effects. Authors highlight the clinical distinctive
      features of genetic/syndromic causes for childhood obesity, in particular,
      relative shorter height to their genetic potential, developmental challenges and
      in some instances, ophthalmological and retina changes. They outline specific
      genetic testing and treatment options available for these conditions.

PMID- 29177812
TI  - Anaerobic degradation of 1-methylnaphthalene by a member of the
      Thermoanaerobacteraceae contained in an iron-reducing enrichment culture.
AB  - An anaerobic culture (1MN) was enriched with 1-methylnaphthalene as sole source
      of carbon and electrons and Fe(OH)3 as electron acceptor. 1-Naphthoic acid was
      produced as a metabolite during growth with 1-methylnaphthalene while 2-naphthoic
      acid was detected with naphthalene and 2-methylnaphthalene. This indicates that
      the degradation pathway of 1-methylnaphthalene might differ from naphthalene and
      2-methylnaphthalene degradation in sulfate reducers. Terminal restriction
      fragment length polymorphism and pyrosequencing revealed that the culture is
      mainly composed of two bacteria related to uncultured Gram-positive
      Thermoanaerobacteraceae and uncultured gram-negative Desulfobulbaceae. Stable
      isotope probing showed that a 13C-carbon label from 13C10-naphthalene as growth
      substrate was mostly incorporated by the Thermoanaerobacteraceae. The presence of
      putative genes involved in naphthalene degradation in the genome of this organism
      was confirmed via assembly-based metagenomics and supports that it is the
      naphthalene-degrading bacterium in the culture. Thermoanaerobacteraceae have
      previously been detected in oil sludge under thermophilic conditions, but have
      not been shown to degrade hydrocarbons so far. The second member of the community
      belongs to the Desulfobulbaceae and has high sequence similarity to uncultured
      bacteria from contaminated sites including recently proposed groundwater cable
      bacteria. We suggest that the gram-positive Thermoanaerobacteraceae degrade
      polycyclic aromatic hydrocarbons while the Desulfobacterales are mainly
      responsible for Fe(III) reduction.

PMID- 29177813
TI  - Micro-CT evaluation of voids using two root filling techniques in the placement
      of MTA in mesial root canals of Vertucci type II configuration.
AB  - OBJECTIVE: The present study aims to compare two mineral trioxide aggregate (MTA)
      placement techniques, manual compaction and ultrasonic activation of manually
      compacted MTA, with warm vertical compaction (WVC) for orthograde obturation of
      mesial root canals of mandibular first molars showing Vertucci type II root canal
      configuration. MATERIALS AND METHODS: Thirty roots were selected according to
      their micro-CT scanned images. Root canals were chemomechanically prepared using
      Reciproc R25 and NaOCl using EndoVac. The specimens were divided into three
      groups according to the root canal filling technique, as manual compaction of
      MTA, ultrasonic activation of manually compacted MTA and WVC using gutta-percha
      and AH Plus (Denstply Sirona, Ballaigues, Switzerland). Percentages of voids
      located in apical 3 mm and remaining coronal half until the level where separate
      root canals re-join within filling were calculated. Data were analyzed using the
      Kruskal-Wallis and Dunn's tests, and significance was set at 5%. RESULTS: No
      significant difference was found among the filling techniques regarding the
      percentage volume of voids at apical 3 mm (P > 0.05). At the coronal half of the
      isthmus, WVC produced significantly less percentage volume of voids than manual
      compaction of MTA (P < 0.05) and similar to ultrasonic activation group did (P >
      0.05). There was no significant difference between two MTA placement techniques
      at the coronal half of the isthmus (P > 0.05). CONCLUSIONS: No filling technique
      produced void-free fillings. The percentage of void volume was similar among
      groups at apical 3 mm but was different at the coronal half of the isthmus.
      CLINICAL RELEVANCE: Warm vertical compaction and ultrasonically activated MTA
      fillings revealed similar quality at the isthmus area, which was superior to
      manually compacted MTA.

PMID- 29177814
TI  - Orofacial manifestations in outpatients with anorexia nervosa and bulimia nervosa
      focusing on the vomiting behavior.
AB  - OBJECTIVE: This case-control study aims to evaluate the oral health status and
      orofacial problems in a group of outpatients with eating disorders (ED)-either
      anorexia nervosa (AN) or bulimia nervosa (BN)-further focusing on the influence
      of vomit. MATERIALS AND METHODS: Fifty-five women outpatients with AN or BN
      diagnosis were invited to participate, of which 33 agreed. ED outpatients and
      matched controls were submitted to a questionnaire and clinical oral examination.
      RESULTS: Multivariate analysis identified a significantly higher incidence of
      teeth-related complications (i.e., tooth decay, dental erosion, and self-reported
      dentin hypersensitivity), periodontal disease, salivary alterations (i.e.,
      hyposalivation and xerostomia), and oral mucosa-related complications in ED
      outpatients. Dental erosion, self-reported dentin hypersensitivity,
      hyposalivation, xerostomia, and angular cheilitis were found to be highly
      correlated with the vomiting behavior. CONCLUSIONS: ED outpatients were found to
      present a higher incidence of oral-related complications and an inferior oral
      health status, compared to gender- and age-matched controls. Alterations verified
      within outpatients were acknowledged to be quite similar to those previously
      reported within inpatients, in both of nature and severity, thus sustaining that
      the cranio-maxillofacial region is significantly affected by ED, even in the
      early/milder forms of the condition, as expectedly verified within outpatients.

PMID- 29177815
TI  - A Database Cohort Study to Assess the Risk of Angioedema Among Patients with
      Heart Failure Initiating Angiotensin-Converting Enzyme Inhibitors in the USA.
AB  - INTRODUCTION: Real-world evidence on the risk of angioedema associated with
      angiotensin-converting enzyme inhibitors (ACEIs) in patients with heart failure
      (HF) is scarce. OBJECTIVE: This non-interventional study aimed to estimate the
      incidence of and risk factors for angioedema in patients with HF initiating an
      ACEI in real-world practice. METHODS: This was a retrospective cohort study using
      claims data from the PharMetrics Plus database, supplemented with consumer health
      data, from 1 January 2007 to 31 March 2015. Patients with HF initiating an ACEI
      were followed up for a maximum of 1 year, until the first occurrence of
      angioedema or until cohort exit. Angioedema incidence rates were estimated and
      stratified by potential risk factors such as race, age, sex, and time from
      initiation of ACEI therapy. For each risk factor, the unadjusted and adjusted
      hazard ratio (HR) was calculated; exploratory analyses were carried out to
      account for all potential confounders. RESULTS: We identified 21,639 patients
      with HF initiating an ACEI (mean age 58 years; 35.6% women; mean follow-up 205
      days). The 1-year incidence of angioedema per 1000 patient-years was 3.3 [95%
      confidence interval (CI) 2.4-4.5]. The incidence was higher in Black [6.2 (95% CI
      3.1-12.5)] than in non-black [2.9 (95% CI 2.1-4.1)] patients, higher in women
      [5.2 (95% CI 3.4-7.9)] than in men [2.3 (95% CI 1.5-3.6)], and greatest in the
      first 30 days of ACEI therapy. CONCLUSIONS: The risk of angioedema in patients
      with HF initiating an ACEI observed in this study is in line with published
      estimates for the general patient population treated with ACEIs.

PMID- 29177816
TI  - Frames of Reference and Antecedentless Anaphora in Spanish Conversation.
AB  - This study examines native Spanish speakers' use of anaphoric pronouns and null
      subjects in conversational discourse in the absence of coreferential antecedents.
      It also considers the adequacy of Gundel et al.'s proposal  (Language 69(2):274
      307, 1993) that the cognitive status "in focus" corresponds with speakers' use of
      minimal referring expressions (i.e., unstressed pronouns and zeros). Analysis of
      naturally occurring Spanish conversation shows how the felicitous use and
      interpretation of non-canonical (antecedentless) anaphoric pronouns and null
      subjects are possible due to the activation of underlying cognitive frames that
      are shared by the interlocutors. Furthermore, the speaker's mention of a
      referent, dubbed a "neighborhood antecedent" by Langacker (Conceptual grouping
      and pronominal anaphora, in: Fox (ed) Studies in anaphora, Cambridge University
      Press, Cambridge, 1996), and the information "filled in" over the course of the
      conversation on account of the activation of relevant cognitive frames, both
      license and disambiguate the non-canonical anaphoric relations.

PMID- 29177817
TI  - Modulation of dual-task control with right prefrontal transcranial direct current
      stimulation (tDCS).
AB  - Executive functioning of two simultaneous component tasks in dual-task situations
      is primarily associated with activation of the lateral prefrontal cortex (PFC),
      as demonstrated in functional imaging studies. However, the precise role of the
      lateral PFC and the causal relation between this area's activity and executive
      functioning in dual tasks has exclusively been demonstrated for the left lateral
      PFC so far. To investigate this relation for the right lateral PFC, we used
      anodal transcranial direct current stimulation (atDCS; 1 mA, 20 min) in contrast
      to sham stimulation (1 mA, 30 s) in Experiment 1 (N = 30) as well as cathodal
      transcranial direct current stimulation (ctDCS; 1 mA, 20 min) in contrast to sham
      stimulation (1 mA, 30 s) in Experiment 2 (N = 25) over the right inferior frontal
      junction under conditions of random task order in dual tasks; random dual tasks
      require decisions on task order and thus high demands on executive functioning.
      Across these experiments, our results showed different tDCS-related effects:
      while atDCS improved performance evident from reduced error rates (Experiment 1),
      ctDCS impaired dual-task performance and increased these rates (Experiment 2).
      Moreover, baseline performance correlated with tDCS-induced performance changes,
      indicating that baseline performance was associated with atDCS-induced
      improvement. Our findings suggest that dual-task performance is causally related
      to right lateral PFC activation under conditions that require executive
      functioning as well as cognitive control of task sets and task order.

PMID- 29177818
TI  - Treatment of Cerebellar Ataxia in the Context of Systemic Diseases.
AB  - Purpose of review The purpose of this review is to assess the evidence behind
      treatment regimens for cerebellar ataxias occurring in the context of systemic
      disease. We will address systemic conditions which are associated with specific
      involvement of the cerebellum (rather than widespread nervous system involvement)
      and those conditions for which some degree of evidence of treatment response
      exists. Recent findings We have divided systemic disorders affecting the
      cerebellum into systemic immunological disorders, endocrine and metabolic
      disorders and paraneoplastic. Recent studies have increased understanding of the
      range of cerebellar disorders associated with a systemic immunological condition.
      The identification of newer pathogenic antibodies has improved diagnosis in
      conditions which would have previously been labelled as idiopathic. However,
      their rarity and phenotypic variability makes defining optimal immunomodulatory
      treatment regimens challenging. There is some evidence for beneficial effects of
      immunomodulation, particularly in anti-GAD ataxia and Hashimoto's encephalopathy,
      although, at this time, specific treatment regimens cannot be defined. Immune
      mediated paraneoplastic cerebellar disorders show response to therapy dependent,
      to some extent, on the underlying pathogenic antibody. Much is still to be
      understood concerning treatment regimens for the ataxic manifestations of
      metabolic disorders, notably alcohol-induced cerebellar injury, which are common
      and which are associated with significant disability. Summary Despite their
      rarity, cerebellar ataxias occurring in the context of systemic disease cause
      significant morbidity and better therapies are required to improve outcomes
      associated with these conditions.

PMID- 29177819
TI  - A case of chronic asymptomatic central pontine myelinolysis with histological
      evidence of remyelination.
AB  - Central pontine myelinolysis (CPM) is a neurological demyelinating disease of the
      pons. Although usually associated with rapid correction of hyponatremia, CPM may
      occur despite normonatremia, is often associated with chronic alcoholism and may
      be asymptomatic. Histological confirmation of asymptomatic CPM is rare. We
      describe an unusual post-mortem case of extensive but asymptomatic CPM in a
      chronic alcoholic patient with normonatremia. The affected part of the pons
      contained thinly myelinated axons with appearances supporting remyelination. We
      suggest that remyelination may account for the subclinical nature of this
      patient's CPM.

PMID- 29177821
TI  - Arterial aneurysms associated with intracranial dural arteriovenous fistulas:
      epidemiology, natural history, and management. A systematic review.
AB  - Arterial aneurysms are uncommon among patients with dural arteriovenous fistulae
      (DAVFs), and there is limited information available to guide treatment decisions
      in such cases. We performed a systematic review of the literature, including a
      case of a DAVF associated with a flow-related intraorbital ophthalmic artery (OA)
      aneurysm that we have recently managed. The purpose of our study was to clarify
      epidemiology, natural history, and management of these lesions. A total of 43
      published cases of DAVF associated aneurysms were found in 26 studies on the
      topic. Anterior cranial fossa was the most common location (40%), and ethmoidal
      branches were the most common arterial feeders (55%). In about 63% of cases, the
      aneurysm was located on artery unrelated to DAVF supply. Approximately 10% of
      intracranial DAVFs were associated with aneurysms located in the intraorbital OA.
      Overall, 70% of lesions were Borden type III, and 50% of patients presented with
      hemorrhage. In approximately 17% of cases, the source of bleeding was a feeding
      artery aneurysm. All of the reported intraorbital OA aneurysms associated with
      DAVFs remained stable during follow-up. DAVF associated aneurysms are fairly
      rare. Anterior cranial fossa location and direct cortical venous drainage are
      common among these lesions. The aneurysms are less likely to be located on
      feeding arteries, and hemorrhagic presentation related to flow-related aneurysm
      rupture is uncommon.

PMID- 29177820
TI  - Single-use flexible ureteropyeloscopy: a systematic review.
AB  - PURPOSE: Data assessing the effectiveness of single-use flexible
      ureteropyeloscopy (FURS) are limited. This study evaluates and compares single
      use FURS with conventional reusable FURS. METHODS: A systematic search using
      electronic databases (Pubmed and Embase) was performed for studies evaluating
      single-use FURS in the setting of urinary tract stone disease. Outcome measures
      included a comparative evaluation of their mechanical, optical and clinical
      outcomes. RESULTS: Eleven studies on 466 patients met inclusion criteria. In
      vitro comparative data were available on three single-use flexible
      ureteropyeloscopes (LithoVueTM, PolyscopeTM and SemiFlexTM) and clinical data
      were available on two (LithoVueTM and PolyscopeTM). The overall stone-free rate
      and complication rate associated with single-use FURS was 87 +/- 15% and 9.3 +/-
      9%, respectively. There were no significant differences in procedure duration,
      stone size, stone clearance and complication rates when single-use FURS and
      reusable FURS were compared (duration: 73 +/- 27 versus 74 +/- 13 min, p = 0.99;
      stone size: 1.36 +/- 0.2 versus 1.34 +/- 0.18 cm, p = 0.93; stone-free rate: 77.8
      +/- 18 versus 68.5 +/- 33%, p = 0.76; complication rate 15.3 +/- 10.6 versus 15
      +/- 1.6%, p = 0.3). CONCLUSIONS: Single-use FURS demonstrates comparable efficacy
      with reusable FURS in treating renal calculi. Further studies on clinical
      efficacy and cost are needed to determine whether single-use FURS will reliably
      replace its reusable counterpart.

PMID- 29177822
TI  - High-Resolution Crystallographic Analysis of AcrB Using Designed Ankyrin Repeat
      Proteins (DARPins).
AB  - X-ray crystallography is still the most prominent technique in use to decipher
      the 3D structures of membrane proteins. For successful crystallization, sample
      quality is the most important parameter that should be addressed. In almost every
      case, highly pure, monodisperse, and stable protein sample is a prerequisite.
      Vapor diffusion is in general the method of choice for obtaining crystals. Here,
      we discuss a detailed protocol for overproduction and purification of the inner
      membrane multidrug transporter AcrB and of DARPins, which are used for
      crystallization of the AcrB/DARPin complex, resulting in high-resolution
      diffraction and subsequent structure determination.

PMID- 29177823
TI  - Crystallographic Analysis of Drug and Inhibitor-Binding Structure of RND-Type
      Multidrug Exporter AcrB in Physiologically Relevant Asymmetric Crystals.
AB  - Xenobiotic extruding pumps have recently been known to be widely distributed in
      living organisms from mammalian to bacteria as a host-defense mechanism in
      cellular level. These pumps not only confer multidrug resistance of cancer cells
      and pathogenic bacteria but also cause hereditary diseases through the mutation.
      Our purposes are to elucidate the molecular structures and mechanisms of these
      xenobiotic exporters.We had succeeded to determine the crystal structure of
      bacterial major multidrug exporter AcrB at 3.5 A resolution (Murakami et al.,
      Nature 419:587-593, 2002) and elucidated the structural bases of substrate
      recognition that the pump recognize the places and thus act as a "membrane vacuum
      cleaner." After that we also determined the crystal structure of the drug-binding
      form of AcrB in space group C2 in which asymmetric unit contains structurally
      asymmetric homo-trimer of AcrB (Murakami et al., Nature 443:173-179, 2006;
      Nakashima et al., Nature 480:565-569, 2011; Nakashima et al., Nature 500:120-126,
      2013). Analyses revealed the existence of a specific mechanism to recognize
      numerous substrates that the multisite binding is the base of multidrug
      recognition rather than induced-fit, and functional-rotation mechanism in which
      three monomers undergo a strictly coordinated sequential conformational change
      cycle of access, binding, and extrusion. Determination of physiological
      asymmetric AcrB structure was crucially important to understand these transport
      mechanisms.

PMID- 29177824
TI  - Crystallographic Analysis of MATE-Type Multidrug Exporter with Its Inhibitors.
AB  - Multidrug exporters expressed in pathogens efflux substrate drugs such as
      antibiotics, and thus, the development of inhibitors against them has eagerly
      been anticipated. Furthermore, the crystal structures of multidrug exporters with
      their inhibitors provide novel insights into the inhibitory mechanism and the
      development of more specific and effective inhibitors. We previously reported the
      complex structures of the Multidrug And Toxic compound Extrusion (MATE)-type
      multidrug exporter with the macrocyclic peptides, which inhibit the efflux of
      substrates by the MATE-type multidrug exporter (Tanaka et al., Nature 496:247
      251, 2013). In this chapter, we describe methodologies of the screening and
      synthesis of macrocyclic peptides as inhibitors, as well as the purification,
      crystallization, and structure determination of the complexes of the MATE-type
      multidrug exporter with its inhibitors.

PMID- 29177825
TI  - Crystallographic Analysis of the CusBA Heavy-Metal Efflux Complex of Escherichia
      coli.
AB  - Crystallization is one of the most successful techniques used to determine
      protein structure, especially for membrane proteins. However, the application of
      this technique is not straightforward and often hampered by the difficulties
      associated with expression, purification, and crystallization. Here we present
      our protocol and methodology for crystallizing the CusBA adaptor-transporter
      complex of Escherichia coli. Using these procedures, we were able to produce the
      first co-crystal structure of a resistance-nodulation-cell division (RND)
      transporter in complex with its associated membrane fusion protein.

PMID- 29177826
TI  - Purification of AcrAB-TolC Multidrug Efflux Pump for Cryo-EM Analysis.
AB  - The cell envelope of Gram-negative bacteria comprises an outer membrane, a
      cytoplasmic inner membrane, and an interstitial space. The tripartite multidrug
      transporter AcrAB-TolC, which uses proton electrochemical gradients to
      vectorially drive the efflux of drugs from the cell, spans this envelope. We
      describe here details of the methods used to prepare the recombinant tripartite
      assembly for high-resolution structure determination by cryo-EM.

PMID- 29177827
TI  - NMR Spectroscopy Approach to Study the Structure, Orientation, and Mechanism of
      the Multidrug Exporter EmrE.
AB  - Multidrug exporters are a class of membrane proteins that remove antibiotics from
      the cytoplasm of bacteria and in the process confer multidrug resistance to the
      organism. This chapter outlines the sample preparation and optimization of
      oriented solid-state NMR experiments applied to the study of structure and
      dynamics for the model transporter EmrE from the small multidrug resistance (SMR)
      family.

PMID- 29177828
TI  - Generation of Conformation-Specific Antibody Fragments for Crystallization of the
      Multidrug Resistance Transporter MdfA.
AB  - A major hurdle in membrane protein crystallography is generating crystals
      diffracting sufficiently for structure determination. This is often attributed
      not only to the difficulty of obtaining functionally active protein in mg amounts
      but also to the intrinsic flexibility of its multiple conformations. The
      cocrystallization of membrane proteins with antibody fragments has been reported
      as an effective approach to improve the diffraction quality of membrane protein
      crystals by limiting the intrinsic flexibility. Isolating suitable antibody
      fragments recognizing a single conformation of a native membrane protein is not a
      straightforward task. However, by a systematic screening approach, the time to
      obtain suitable antibody fragments and consequently the chance of obtaining
      diffracting crystals can be reduced. In this chapter, we describe a protocol for
      the generation of Fab fragments recognizing the native conformation of a major
      facilitator superfamily (MFS)-type MDR transporter MdfA from Escherichia coli. We
      confirmed that the use of Fab fragments was efficient for stabilization of MdfA
      and improvement of its crystallization properties.

PMID- 29177829
TI  - Biochemical Reconstitution and Characterization of Multicomponent Drug Efflux
      Transporters.
AB  - Efflux pumps are the major determinants in bacterial multidrug resistance. In
      Gram-negative bacteria, efflux transporters are organized as macromolecular
      tripartite machineries that span the two-membrane cell envelope of the bacterium.
      Biochemical data on purified proteins are essential to draw a mechanistic picture
      of this highly dynamical, multicomponent, efflux system. We describe protocols
      for the reconstitution and the in vitro study of transporters belonging to RND
      and ABC superfamilies: the AcrAB-TolC and MacAB-TolC efflux systems from
      Escherichia coli and the MexAB-OprM efflux pump from Pseudomonas aeruginosa.

PMID- 29177830
TI  - Covalently Linked Trimers of RND (Resistance-Nodulation-Division) Efflux
      Transporters to Study Their Mechanism of Action: Escherichia coli AcrB Multidrug
      Exporter as an Example.
AB  - Transporters undergo large conformational changes in their functional cycle. RND
      (Resistance-Nodulation-Division) family efflux transporters usually exist as
      homotrimers, and each protomer was proposed to undergo a cycle of conformational
      changes in succession so that at any given time the trimer would contain three
      protomers of different conformations, the functionally rotating mechanism of
      transport. This mechanism implies that the inactivation of one protomer among
      three will inactivate the entire trimeric ensemble by blocking the functional
      rotation. We describe a biochemical approach to test this prediction by first
      producing a giant protein in which the three protomers of Escherichia coli AcrB
      efflux pump are covalently linked together through linker sequences, and then
      testing for its function by inactivation of a single protomer unit. Inactivation
      can be done permanently by mutating a residue involved in proton relay, or in
      "real time" by using a protein in which one protomer contains two Cys residues on
      both sides of the large cleft in the periplasmic domain and then by rapidly
      inactivating this protomer with a methanethiosulfonate cross-linker.

PMID- 29177831
TI  - Determining Ligand Path Through a Major Drug Transporter, AcrB, in Escherichia
      coli.
AB  - An experimental approach to detect the path a substrate takes through a complex
      membrane protein is described with emphasis on technical approach and theoretical
      considerations. The protocols for bacterial culture preparation, membrane protein
      purification, fluorescent assay standardization, data collection, and data
      analysis are provided. Useful software tools are recommended.

PMID- 29177832
TI  - Molecular Modeling of Multidrug Properties of Resistance Nodulation Division
      (RND) Transporters.
AB  - Efflux pumps of the resistance nodulation division (RND) superfamily are among
      the major contributors to intrinsic and acquired multidrug resistance in Gram
      negative bacteria. Structural information on AcrAB-TolC and MexAB-OprM, major
      efflux pumps of Escherichia coli and Pseudomonas aeruginosa respectively, boosted
      intensive research aimed at understanding the molecular mechanisms ruling the
      active extrusion processes. In particular, several studies were devoted to the
      understanding of the determinants behind the extraordinary broad specificity of
      the RND transporters AcrB and MexB. In this chapter, we discuss the ever-growing
      role computational methods have been playing in deciphering key structural and
      dynamical features of these transporters and of their interaction with substrates
      and inhibitors. We further discuss and illustrate examples from our lab of how
      molecular docking, homology modeling, all-atom molecular dynamics simulations and
      in silico free energy estimations can all together give precious insights into
      the processes of recognition and extrusion of substrates, as well as on the
      possible inhibition strategies.

PMID- 29177833
TI  - A Transcriptomic Approach to Identify Novel Drug Efflux Pumps in Bacteria.
AB  - The core genomes of most bacterial species include a large number of genes
      encoding putative efflux pumps. The functional roles of most of these pumps are
      unknown, however, they are often under tight regulatory control and expressed in
      response to their substrates. Therefore, one way to identify pumps that function
      in antimicrobial resistance is to examine the transcriptional responses of efflux
      pump genes to antimicrobial shock. By conducting complete transcriptomic
      experiments following antimicrobial shock treatments, it may be possible to
      identify novel drug efflux pumps encoded in bacterial genomes. In this chapter we
      describe a complete workflow for conducting transcriptomic analyses by RNA
      sequencing, to determine transcriptional changes in bacteria responding to
      antimicrobials.

PMID- 29177834
TI  - Regulation of the Expression of Bacterial Multidrug Exporters by Two-Component
      Signal Transduction Systems.
AB  - Bacterial multidrug exporters confer resistance to a wide range of antibiotics,
      dyes, and biocides. Recent studies have shown that there are many multidrug
      exporters encoded in bacterial genome. For example, it was experimentally
      identified that E. coli has at least 20 multidrug exporters. Because many of
      these multidrug exporters have overlapping substrate spectra, it is intriguing
      that bacteria, with their economically organized genomes, harbor such large sets
      of multidrug exporter genes. The key to understanding how bacteria utilize these
      multiple exporters lies in the regulation of exporter expression. Bacteria have
      developed signaling systems for eliciting a variety of adaptive responses to
      their environments. These adaptive responses are often mediated by two-component
      regulatory systems. In this chapter, the method to identify response regulators
      that affect expression of multidrug exporters is described.

PMID- 29177835
TI  - Study of the Expression of Bacterial Multidrug Efflux Pumps in Anaerobic
      Conditions.
AB  - Bacterial multidrug efflux pumps belong to a class of membrane transporter
      proteins that dedicate to the extrusion of a diverse range of substances out of
      cells including all classes of currently available antibiotics. They constitute
      an important mechanism of bacterial antibiotic and multidrug resistance. Since
      many ecological niches of bacteria and the infection foci in animal host display
      low oxygen tension under which condition bacterial pathogens undergo fundamental
      changes on their metabolic modes, it is necessary to study the expression
      profiles of drug efflux pumps under these physiologically and clinically relevant
      conditions. In this chapter, we first introduce procedures to culture bacteria
      under anaerobic conditions, which is achieved using screw-capped Pyrex culture
      tubes without agitation. We then introduce beta-galactosidase activity assay
      using promoter-lacZ (encoding the beta-galactosidase enzyme) fusion to measure
      the expression of efflux pumps at transcriptional level, and Western blot using
      chromosomal FLAG-tagged construct to examine the expression of these proteins at
      translational level. Applications of these gene expression studies to reveal the
      regulatory mechanisms of efflux genes expression as well as their physiological
      functions are also discussed.

PMID- 29177836
TI  - Identification of a Staphylococcus aureus Efflux Pump Regulator Using a DNA
      Protein Affinity Technique.
AB  - In this chapter, we describe the step-by-step identification of a putative
      regulator protein and demonstrate the function of this protein as a repressor of
      the expression of a specific efflux pump, causing resistance to quinolones in
      Staphylococcus aureus. We show that the knockout gene mutant has an increase in
      transcript levels of the target efflux pump when compared to that of the S.
      aureus parental strain RN6390. We provide a detailed protocol that includes the
      identification of the DNA-binding transcriptional regulatory protein from S.
      aureus cell extracts using DNA sequences linked to magnetic beads. In addition,
      we describe the real-time qRT-PCR assays and MIC testing to evaluate the effects
      of the regulator on S. aureus drug resistance phenotype.

PMID- 29177837
TI  - High-Throughput Flow Cytometry Screening of Multidrug Efflux Systems.
AB  - The resistance nodulation cell division (RND) family of proteins are inner
      membrane transporters that associate with periplasmic adaptor proteins and outer
      membrane porins to affect substrate transport from the cytosol and periplasm in
      Gram-negative bacteria. Various structurally diverse compounds are substrates of
      RND transporters. Along with their notable role in antibiotic resistance, these
      transporters are essential for niche colonization, quorum sensing, and virulence
      as well as for the removal of fatty acids and bile salts. As such, RNDs are an
      attractive target for antimicrobial development. However, while enhancing the
      utility of antibiotics with an RND inhibitor is an appealing concept, only a
      small core of chemotypes has been identified as efflux pump inhibitors (EPIs).
      Thus, our key objective is the development and validation of an efflux profiling
      and discovery strategy for RND model systems. Here we describe a flow cytometric
      dye accumulation assay that uses fluorescein diacetate (FDA) to interrogate the
      model Gram-negative pathogens Escherichia coli, Franscisella tularensis, and
      Burkholderia pseudomallei. Fluorochrome retention is increased in the presence of
      known efflux inhibitors and in RND deletion strains. The assay can be used in a
      high-throughput format to evaluate efflux of dye-substrate candidates and to
      screen chemical libraries for novel EPIs. Triaged compounds that inhibit efflux
      in pathogenic strains are tested for growth inhibition and antibiotic
      potentiation using microdilution culture plates in a select agent Biosafety Level
      3 (BSL3) environment. This combined approach demonstrates the utility of flow
      cytometric analysis for efflux activity and provides a useful platform in which
      to characterize efflux in pathogenic Gram-negative bacteria. Screening small
      molecule libraries for novel EPI candidates offers the potential for the
      discovery of new classes of antibacterial compounds.

PMID- 29177838
TI  - Single-Molecule Analysis of Membrane Transporter Activity by Means of a
      Microsystem.
AB  - Emerging microtechnologies are aimed at developing a microsystem with densely
      packed array structure, i.e., an array with a femtoliter reaction chamber, for
      highly sensitive and quantitative biological assays. Here, we describe a novel
      femtoliter chamber array system (arrayed lipid bilayer chambers, ALBiC) that
      contains approximately a million femtoliter chambers, each sealed with a
      phospholipid bilayer membrane with extremely high efficiency (>90%). This novel
      platform enables detection of membrane transporter activity at the single
      molecule level and thus expands the applicability of femtoliter chamber arrays to
      highly sensitive assays of transporters.

PMID- 29177839
TI  - Large-Scale Femtoliter Droplet Array for Single Cell Efflux Assay of Bacteria.
AB  - Large-scale femtoliter droplet array as a platform for single cell efflux assay
      of bacteria is described. Device microfabrication, femtoliter droplet array
      formation and concomitant enclosure of single bacterial cells, fluorescence-based
      detection of efflux activity at the single cell level, and collection of single
      cells from droplet and subsequent gene analysis are described in detail.

PMID- 29177840
TI  - Reconstitution and Transport Analysis of Eukaryotic Transporters in the Post
      Genomic Era.
AB  - Measuring transport activity through reconstituted proteoliposomes is a key
      technique to resolve numerous problems found in the traditional methods. The
      system includes overexpression, purification, and reconstitution of transporters.
      Mixing of purified transporter with lipid and dilution below the critical micelle
      concentration result in rapid generation of proteoliposomes. Incubation of
      proteoliposomes in the presence of a driving force initiates substrate uptake.
      After starting the reaction, samples are passed through a gel filtration column
      to separate proteoliposomes from the reaction mixture. Here, we describe step-by
      step procedures for such reconstitution assays.

PMID- 29177841
TI  - Xanthogranulomatous pyelonephritis: a case with rare adhesion to pancreas.
AB  - Xanthogranulomatous pyelonephritis (XGP) is a rare benign condition with unknown
      aetiology and chronic infection of kidney. Commonly, most cases are related with
      urinary tract obstruction, nephrolithiasis, infection, diabetes, and/or immune
      compromise. XGP is associated with destruction of the renal parenchyma and
      granulomatous inflammation with foamy lipid-laden macrophages resulting from
      obstructive uropathy. It closely mimics a malignancy, exhibiting local tissue
      invasion and destruction. Adjacent organs especially duodenum as well as very
      rarely pancreas or spleen may be involved. Additionally, XGP is known as
      notorious for fistulisations, such as pyelocutaneous and ureterocutaneous
      fistulae, which have been reported as well described. XGP may be
      indistinguishable from renal cell carcinoma by radiographic and clinic
      consultation so it must be diagnosed based on the histopathologic examinations.
      Furthermore, macroscopic appearance of XGP is a mass of yellow tissue with focal
      haemorrhage besides necrosis and in this regard, it grossly resembles renal cell
      carcinoma. Here, we report the case of a 32-year-old female, preoperatively
      diagnosed as malignancy by clinical examination. Our further pathological
      evaluations revealed very rarely adhesion of XGP to pancreas tissue.

PMID- 29177842
TI  - Trifluridine-Tipiracil for Previously Treated Metastatic Colorectal Cancer: An
      Evidence Review Group Perspective of a NICE Single Technology Appraisal.
AB  - The National Institute for Health and Care Excellence (NICE) invited Servier, the
      company manufacturing trifluridine and tipiracil (T/T; trade name: Lonsurf(r)),
      to submit evidence for the clinical and cost effectiveness of T/T compared with
      best supportive care (BSC) for metastatic colorectal cancer (third-line or
      later). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht
      University Medical Center, was commissioned as the Evidence Review Group (ERG).
      This paper presents a summary of the company's submission (CS), the ERG report
      and the development of the NICE guidance for the use of this drug in England and
      Wales by the appraisal committee (AC). The ERG produced a critical review of the
      clinical and cost effectiveness of T/T based upon the CS. In the CS, pooled
      evidence of two trials (a phase II trial and RECOURSE) showed that T/T resulted
      in a significant increase in overall survival [OS; hazard ratio (HR) 0.67, 95% CI
      0.58-0.78] and progression-free survival (PFS; HR 0.46, 95% CI 0.40-0.53). The AC
      considered the survival benefit of T/T clinically meaningful although relatively
      small. The ERG highlighted that none of the participants in the phase II trial
      and approximately half of the RECOURSE participants (394 of 800) were from
      Europe, which might limit the applicability of the study findings to the NHS.
      Moreover, the ERG's critical assessment of the company's economic evaluation
      highlighted a number of concerns that resulted in 11 adjustments to the company's
      base-case analysis. The ERG adjustments that had the largest impact were using
      the RECOURSE trial data only (instead of the pooled evidence), fixing errors and
      violations and using the utilities from the CORRECT trial (identified in the
      literature review) only. The ERG preferred to use the RECOURSE trial data only
      given the suboptimal methodology used by the company to pool the evidence.
      However, since there were no fundamental arguments to prevent the two trials from
      being pooled, the ERG also presented its base-case analysis based on the pooled
      effectiveness estimates. The company base-case resulted in an incremental cost
      effectiveness ratio (ICER) of L44,032 per QALY gained while the ERG base-case
      resulted in ICERs of L52,695 and L49,392 per QALY gained based on the RECOURSE
      trial only and pooled evidence, respectively. Since the AC concluded that the
      most plausible ICER was L49,392 per QALY gained, and that T/T meets end-of-life
      criteria, T/T was recommended as a cost effective use of NHS resources.

PMID- 29177843
TI  - Stabilising selection on immune response in male black grouse Lyrurus tetrix.
AB  - Illnesses caused by a variety of micro- and macro- organisms can negatively
      affect individuals' fitness, leading to the expectation that immunity is under
      positive selection. However, immune responses are costly and individuals must
      trade-off their immune response with other fitness components (e.g. survival or
      reproductive success) meaning that individuals with intermediate response may
      have the greatest overall fitness. Such a process might be particularly acute in
      species with strong sexual selection because the condition-dependence of male
      secondary sexual-traits might lead to striking phenotypic differences amongst
      males of different immune response levels. We tested whether there is selection
      on immune response by survival and reproduction in yearling and adult male black
      grouse (Lyrurus tetrix) following an immune challenge with a novel antigen and
      tested the hypothesis that sexual signals and body mass are honest signals of the
      immune response. We show that yearling males with highest immune response to
      these challenges had higher survival, but the reverse was true for adults. Adults
      with higher responses had highest mass loss and adult males with intermediate
      immune response had highest mating success. Tail length was related to baseline
      response in adults and more weakly in yearlings. Our findings reveal the complex
      fitness consequences of mounting an immune response across age classes. Such
      major differences in the direction and magnitude of selection in multiple fitness
      components is an alternative route underpinning the stabilising selection of
      immune responses with an intermediate immune response being optimal.

PMID- 29177844
TI  - Analysis of major paralogs encoding the Fra a 1 allergen based on their organ
      specificity in Fragaria * ananassa.
AB  - KEY MESSAGE: Fra a 1 protein in strawberry causes oral allergic syndrome. Over 39
      Fra a 1 paralogs have been identified in strawberry genome. Fra a 1.01 is major
      accumulating protein in edible organs. Strawberry fruits contain allergenic
      proteins that cause oral allergic syndrome. The hypothesized major allergen is
      Fra a 1, an ortholog of the birch pollen allergen protein Bet v 1. We organized
      Fra a 1 genes and analyzed their localizations at the transcriptional and
      translational levels. In total, 15 new Fra a 1 proteins were identified from the
      genomic database, increasing the total number of Fra a 1 to 30 proteins encoded
      by 39 genes. Fra a 1.02 was mostly expressed in receptacles, and Fra a 1.01 in
      achenes, when analyzed by RNA sequencing. Immunoblotting showed that the Fra a
      1.01 protein was broadly accumulated in strawberry organs, while the Fra a 1.02
      protein was mostly expressed in receptacles. Recombinant Fra a 1.01 strongly
      reacted with human IgE. The mRNA and protein expression levels of Fra a 1 did not
      correlate, indicating the importance of protein levels when evaluating the
      abundance of allergens in strawberry. Based on the localizations, accumulation
      levels and reactivity to human IgE, we determined that Fra a 1.01 was the most
      important allergen, followed by Fra a 1.02, and then other Fra a 1 proteins. The
      information obtained here will be useful for selecting the target Fra a 1
      paralogs when breeding hypoallergenic strawberry.

PMID- 29177845
TI  - Regulation of gaseous signaling molecules on proline metabolism in plants.
AB  - Proline accumulation plays an important role in the response and adaptation of
      plants to abiotic stress. Gaseous signaling molecules such as nitric oxide (NO),
      carbon monoxide (CO), and hydrogen sulfide (H2S) are involved in complicated
      events of cell signaling. However, the regulatory mechanisms of gaseous signaling
      molecules on proline synthesis and degradation are still unclear. This review
      summarized the biosynthesis and degradation of proline. The role of gaseous
      signaling molecules and their cross-talk on proline metabolic regulation in
      plants was discussed along with the future perspectives.

PMID- 29177847
TI  - Theoretical investigation of the effects of the molar ratio and solvent on the
      formation of the pyrazole-nitroamine cocrystal explosive 3,4-dinitropyrazole
      (DNP)/2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20).
AB  - The effects of the molar ratio, temperature, and solvent on the formation of the
      cocrystal explosive DNP/CL-20 were investigated using molecular dynamics (MD)
      simulation. The cocrystal structure was predicted through Monte Carlo (MC)
      simulation and using first-principles methods. The results showed that the DNP/CL
      20 cocrystal might be more stable in the molar ratio 1:1 near to 318 K, and the
      most probable cocrystal crystallizes in the triclinic crystal system with the
      space group P[Formula: see text]. Cocrystallization was more likely to occur in
      methanol and ethanol at 308 K as a result of solvent effects. The optimized
      structure and the reduced density gradient (RDG) of the DNP/CL-20 complex
      confirmed that the main driving forces for cocrystallization were a series of
      hydrogen bonds and van der Waals forces. Analyses of the trigger bonds, the
      charges on the nitro groups, the electrostatic surface potential (ESP), and the
      free space per molecule in the cocrystal lattice were carried out to further
      explore their influences on the sensitivity of CL-20. The results indicated that
      the DNP/CL-20 complex tended to be more stable and insensitive than pure CL-20.
      Moreover, an investigation of the detonation performance of the DNP/CL-20
      cocrystal indicated that it possesses high power. Graphical abstract DNP/CL-20
      cocrystal models with different molar ratios were investigated at different
      temperatures using molecular dynamics (MD) simulation methods. Binding energies
      and mechanical properties were probed to determine the stability and performance
      of each cocrystal model. Solvated DNP/CL-20 models were established by adding
      solvent molecules to the cocrystal surface. The binding energies of the models in
      various solvents were calculated in order to identify the most suitable solvent
      and temperature for preparing the cocrystal explosive DNP/CL-20.

PMID- 29177846
TI  - OPEN GLUME1: a key enzyme reducing the precursor of JA, participates in
      carbohydrate transport of lodicules during anthesis in rice.
AB  - KEY MESSAGE: OG1 is involved in JA-regulated anthesis by modulating carbohydrate
      transport of lodicules in rice. Flowering plants have evolved a sophisticated
      regulatory network to coordinate anthesis and maximize reproductive success. In
      addition to various environmental conditions, the plant hormone jasmonic acid and
      its derivatives (JAs) are involved in anthesis. However, the underlying mechanism
      remains largely unexplored. Here, we report a JA-defective mutant in rice (Oryza
      sativa), namely open glume 1, which has dysfunctional lodicules that lead to open
      glumes following anthesis. Map-based cloning and subsequent complementation tests
      confirmed that OG1 encodes a peroxisome-localized 12-oxo-phytodienoic acid
      reductase-a key enzyme that reduces the precursor of JA. Loss-of-function of OG1
      resulted in almost no JA accumulation. Exogenous JA treatment completely rescued
      the defects caused by the og1 mutation. Further studies revealed that
      intracellular metabolism was disrupted in the lodicules of og1 mutant. At the
      mature plant stage, most seeds of the mutant were malformed with significantly
      reduced starch content. We speculate that JA or JA signaling mediates the
      carbohydrate transport of lodicules during anthesis, and signal the onset of cell
      degradation in lodicules after anthesis. We conclude that the OPEN GLUME 1 gene
      that produces a key enzyme involved in reducing the precursor of JA in JA
      biosynthesis and is involved in carbohydrate transport underlying normal lodicule
      function during anthesis in rice.

PMID- 29177848
TI  - Continued Use of a Single Antiplatelet Agent Does Not Increase the Risk of
      Delayed Bleeding After Colorectal Endoscopic Submucosal Dissection.
AB  - BACKGROUND: With the aging of the population and rising incidence of
      thromboembolic events, the usage of antiplatelet agents is also increasing. There
      are few reports yet on the management of antiplatelet agents for patients
      undergoing colorectal endoscopic submucosal dissection (ESD). AIMS: The aim of
      this study is to evaluate whether continued administration of antiplatelet agents
      is associated with an increased rate of delayed bleeding after colorectal ESD.
      METHODS: A total of 1022 colorectal neoplasms in 927 patients were dissected at
      Yokohama City University Hospital and its three affiliate hospitals between July
      2012 and June 2017. We included the data of 919 lesions in the final analysis.
      The lesions were divided into three groups: the no-antiplatelet group (783
      neoplasms), the withdrawal group (110 neoplasms), and the continuation group (26
      neoplasms). RESULTS: Among the 919 lesions, bleeding events occurred in a total
      of 31 (3.37%). The rate of bleeding after ESD was 3.3% (26/783), 4.5% (5/110),
      and 0% (0/26), respectively. There were no significant differences in the rate of
      bleeding after ESD among the three groups (the withdrawal group vs. the no
      antiplatelet group, the continuation group vs. the no-antiplatelet group, and the
      withdrawal group vs. the continuation group). CONCLUSIONS: Continued
      administration of antiplatelet agents is not associated with any increase in the
      risk of delayed bleeding after colorectal ESD. Prospective, randomized studies
      are necessary to determine whether treatment with antiplatelet agents must be
      interrupted prior to colorectal ESD in patients who are at a high risk of
      thromboembolic events.

PMID- 29177849
TI  - Practice Patterns in Hepatitis B Virus Screening Before Cancer Chemotherapy in a
      Major US Hospital Network.
AB  - BACKGROUND: Cancer patients receiving chemotherapy face an increased risk of
      reactivation of chronic hepatitis B virus infection. AIM: To determine the HBV
      screening rate in patients receiving cancer chemotherapy in various clinical
      settings. METHOD: We identified 11,959 adult cancer patients (age >= 18 years)
      receiving parenteral chemotherapy between 2012 and 2015 within a major US
      hospital network, including a large university hospital, community teaching
      hospitals, and community oncology clinics. RESULT: Two thousand and forty-five
      patients (17.1%) were screened for either HBV surface antigen (HBsAg) or HBV core
      antibody (HBcAb) before chemotherapy, and 1850 patients (15.5%) had both HBsAg
      and HBcAb tested before chemotherapy. 8.4% were exposed to HBV, and 0.9% had
      chronic HBV infection (both HBsAg/HBcAb positive). Patients with hematologic
      tumor were more often screened than with solid tumor (55.6 vs. 8.3%, p < 0.001).
      Patients receiving chemotherapy with higher HBV reactivation risk had higher yet
      suboptimal HBV screening rate (41.1% B-depleting agents, 21.5% anthracycline,
      14.9% steroid, 64.7% anti-TNF alpha and 18.6% other chemotherapy, p < 0.001).
      Patients with age >= 50 years (old 16.2% vs. young 23.9%, p < 0.001) and Asian
      ethnicity (Asian 13.6 vs. Caucasian 16.6%, p < 0.001) were screened less for HBV
      despite higher prevalence of HBV exposure (old 9.3% vs. young 4.3%, p < 0.001 and
      Asian 27.8% vs. Caucasian 6.4%, p < 0.001). Patients receiving chemotherapy in
      community oncology clinics were less screened versus community teaching hospitals
      or university hospital (12.7 vs. 19.1 vs. 19.7%, p < 0.001), despite similar
      prevalence of HBV infection. On multivariate analysis, receiving chemotherapy at
      a community oncology clinic [odds ratio (OR) 0.57, 95% confidence interval (CI)
      0.45-0.72, p < 0.001] was independently associated with less HBV screening
      compared to receiving chemotherapy at a university or community teaching
      hospital. CONCLUSION: HBV screening among patients undergoing cancer chemotherapy
      was suboptimal and less commonly performed in community oncology clinics compared
      to teaching hospitals.

PMID- 29177850
TI  - A statistician's perspective on digital epidemiology.
AB  - We address the question "does digital epidemiology represent an epistemic shift
      in infectious disease epidemiology" from a statistician's viewpoint. Our main
      argument is that infectious disease epidemiology has not changed fundamentally as
      it always has been data-driven. However, as the data aspect has become more
      prominent, we discuss the statistical toolbox of the modern epidemiologist and
      argue that problem solving in the digital age, more than ever requires an
      interdisciplinary quantitative approach.

PMID- 29177851
TI  - Investigations into nematode parasites of goats in pastoral and crop livestock
      systems of Ethiopia.
AB  - We generated epidemiological information on the prevalence of nematode parasites
      and possible resistance/resilience of goats in three areas, Bati, Shinille, and
      Borana, of Ethiopia. A total of 350 breeding does were randomly selected and
      monitored for one year. Fecal egg counts (FEC), packed cell volume (PCV), body
      weight (BW), body condition score (BC), and fecal larvae identification were
      done. In Borana, the long rainy season had higher FEC, lower PCV, lower BC, and
      smaller BW compared to dry and short rainy seasons (p < 0.01). For Bati and
      Shinille, the differences between the seasons were significant (p < 0.01) but not
      clear-cut. Breed differences were also evident (p < 0.01) on FEC, PCV, and BW.
      The mean FEC for Borana goat was 158.5 +/- 1.12, whereas for Bati it was 38.9 +/-
      1.12. Age differences did not have effect on FECs, PCV, and BC. No differences in
      parasite load, as reflected by FEC, was verified between male and female goats.
      In the wet season, large numbers of larvae were recovered from the study sites
      except for Bati. In the three sites, Haemonchus contortus followed by
      Trichostrongylus colubriformis were the dominant species. In the dry season,
      however, very little number of larvae was recovered, only of H. contortus in Bati
      and of H. contortus and T. colubriformis in Borana. Generally, the level of
      nematode infection was low. Therefore, nematode parasites are not a major problem
      and strategic control program using broad spectrum anthelmintic is not advisable.
      Rather, monitoring parasite load and selective de-worming should be sufficient to
      reduce productivity loses and pasture contamination.

PMID- 29177852
TI  - Emerging Concepts in Innate Immunity.
AB  - This review introduces recent concepts in innate immunity highlighting some of
      the latest exciting findings. These include: the discovery of the initiator of
      pyroptosis, Gasdermin D, and mechanisms of inflammatory caspases in innate immune
      signaling; the formation of oligomeric signalosomes downstream of innate immune
      receptors; mechanisms that shape innate immune responses, such as cellular
      homeostasis, cell metabolism, and pathogen viability; rapid methods of cell-to
      cell communication; the interplay between the host and its microbiome and the
      concept of innate immunological memory. Furthermore, we discuss open questions
      and illustrate how technological advances, such as CRISPR/Cas9, may provide
      important answers for outstanding questions in the field of innate immunity.

PMID- 29177853
TI  - Bioinformatic Assessment of Macrophage Activation by the Innate Immune System.
AB  - Weighted gene co-expression network analysis (WGCNA) allows for the
      identification and characterization of cell type-specific gene modules in complex
      transcriptome datasets. Here, we use a microarray dataset of human macrophages
      comprising 29 conditions and 299 samples generated by differentiation of CD14+
      monocytes into macrophages followed by in vitro stimulations to identify
      stimulation-specific gene modules. These gene modules can be used for
      experimental validation, as well as further bioinformatic analysis to determine
      key pathways or upstream transcription factors.

PMID- 29177854
TI  - Generation of Genetic Knockouts in Myeloid Cell Lines Using a Lentiviral
      CRISPR/Cas9 System.
AB  - CRISPR/Cas9-based gene targeting allows deletion of a gene of interest from
      cultured cell lines. Due to difficulty in transiently transfecting hematopoetic
      cells with components required for this process, we have adopted a lentiviral
      system for delivery of the CRISPR/Cas9 components into myeloid cell lines. Here,
      we detail the process of knocking out genes from pools of cultured myeloid cells
      using this CRISPR/Cas9 system and describe methods of validating these knockout
      pools.

PMID- 29177855
TI  - Modeling Primary Human Monocytes with the Trans-Differentiation Cell Line BLaER1.
AB  - Monocytes and macrophages play a pivotal role in the induction and shaping of
      immune responses. Expressing a broad array of pattern recognition receptors
      (PRRs), monocytes and macrophages constitute an integral component of the innate
      branch of the immune system. Traditionally, the majority of innate immune sensing
      and signaling pathways have been studied in macrophages of the murine system.
      This is largely due to the fact that genetic loss-of-function studies are
      amenable in this species. On the other hand, human cell lines of the monocyte
      macrophage cell lineage have been widely used to study myeloid cells in vitro.
      However, commonly utilized models (e.g., THP-1 cells) only mimic a limited
      spectrum of the immunobiology of primary human myeloid cells. Recently, we have
      explored the possibility to fill this gap with a human trans-differentiation cell
      culture system, in which lineage conversion from malignant B-lineage cells to
      monocytes/macrophages is caused by the inducible nuclear translocation of a
      C/EBPalpha transgene, BLaER1 cells. Using this model, we were able to
      characterize a novel inflammasome signaling entity that could not have been
      uncovered in the murine system or THP-1 cells. Here, we describe the handling of
      BLaER1 cells, providing a detailed protocol for their induced trans
      differentiation. We also provide data to demonstrate the applicability of the
      BLaER1 monocyte/macrophage system to study phagocytosis and various PRR cascades
      in human cells.

PMID- 29177856
TI  - Measurement of NF-kappaB Activation in TLR-Activated Macrophages.
AB  - Nuclear factor kappa-B (NF-kappaB) is a key transcription factor in the
      regulation of the innate immune inflammatory response in activated macrophages.
      NF-kappaB functions as a homo- or hetero-dimer derived from one or more of the
      five members of the NF-kappaB family, and is activated through a well-studied
      process of stimulus-dependent inhibitor degradation, post-translational
      modification, nuclear translocation, and chromatin binding. Its activity is
      subject to multiple levels of feedback control through both inhibitor protein
      activity and direct regulation of NF-kappaB components. Many methods have been
      developed to measure and quantify NF-kappaB activation. In this chapter, we
      summarize available methods and present a protocol for image-based measurement of
      NF-kappaB activation in macrophages activated with microbial stimuli. Using
      either a stably expressed GFP-tagged fusion of the RelA NF-kappaB protein, or
      direct detection of endogenous RelA by immunocytochemistry, we describe data
      collection and analysis to quantify NF-kappaB cytosol to nuclear translocation in
      single cells using fluorescence microscopy.

PMID- 29177857
TI  - Biochemical Isolation of the Myddosome from Murine Macrophages.
AB  - Ligand-induced macromolecular protein complex formation has emerged as a common
      means by which the innate immune system activates signal transduction pathways
      essential for host defense. Despite their structural divergence, key signaling
      molecules in diverse innate immune pathways mediate signal transduction by
      assembling higher-order protein complexes at specific subcellular locations in a
      stimulus-dependent manner. These protein complexes are collectively known as the
      supramolecular organizing centers (SMOCs), which link active receptors to a
      variety of downstream cellular responses. In the Toll-like receptor (TLR)
      pathway, the signaling adaptor MyD88 is the core of a SMOC called the myddosome,
      which is composed of the sorting adaptor TIRAP and the IRAK family kinases.
      Depending on the microbial ligands encountered, the myddosome can be assembled at
      the plasma membrane or endosomes, thereby leading to NF-KB and AP-1 activation,
      and the subsequent expression of pro-inflammatory cytokines. Herein, we provide a
      detailed protocol for studying myddosome assembly in murine bone marrow-derived
      macrophages (BMDMs).

PMID- 29177858
TI  - Generation of Innate Immune Reporter Cells Using Retroviral Transduction.
AB  - Innate immune cells are notoriously difficult to transfect; however, retroviruses
      can be used to stably integrate genes of interest into the host genome of primary
      or immortalized immune cells resulting in the generation of reporter cells. Here,
      we provide a detailed protocol covering the production of retroviruses,
      retroviral infection of innate immune target cells (including isolation and
      differentiation of murine bone marrow cells to macrophages), and several methods
      for enrichment of positively transduced cells.

PMID- 29177859
TI  - Examining Myddosome Formation by Luminescence-Based Mammalian Interactome Mapping
      (LUMIER).
AB  - Recent structural, biochemical, and functional studies have led to the notion
      that many of the post-receptor signaling complexes in innate immunity have a
      multimeric, multi-protein architecture whose hierarchical assembly is vital for
      function. The Myddosome is a post-receptor complex in the cytoplasmic signaling
      of Toll-like receptors (TLR) and the Interleukin-1 receptor (IL-1R), involving
      the proteins MyD88, IL-1R-associated kinase 4 (IRAK4), and IRAK2. Its importance
      is strikingly illustrated by the fact that rare germline mutations in MYD88
      causing high susceptibility to infections are characterized by failure to
      assemble Myddosomes; conversely, gain-of-function MYD88 mutations leading to
      oncogenic hyperactivation of NF-kappaB show increased Myddosome formation.
      Reliable methods to probe Myddosome formation experimentally are therefore vital
      to further study the properties of this important post-receptor complex and its
      role in innate immunity, such as its regulation by posttranslational
      modification. Compared to structural and biochemical analyses, luminescence-based
      mammalian interactome mapping (LUMIER) is a straightforward, automatable,
      quantifiable, and versatile technique to study protein-protein interactions in a
      physiologically relevant context. We adapted LUMIER for Myddosome analysis and
      provide here a basic background of this technique, suitable experimental
      protocols, and its potential for medium-throughput screening. The principles
      presented herein can be adapted to other signaling pathways.

PMID- 29177860
TI  - Inflammatory Caspases: Activation and Cleavage of Gasdermin-D In Vitro and During
      Pyroptosis.
AB  - Gasdermin-D (also known as GSDMD), the newly identified executioner of pyroptotic
      cell death, is cleaved by activated caspase-1 downstream of canonical
      inflammasome activation or caspase-4, 5, and 11 upon their ligation and
      activation by cytosolic LPS. Upon a single cleavage between the two domains in
      Gasdermin-D, the N-terminal domain binds to membrane lipids and lyses cells by
      forming pores of an inner diameter of 10-14 nm within the membrane. The inter
      domain cleavage of Gasdermin-D is a reliable marker for the activation of
      inflammatory caspases and cell pyroptosis. Here, we describe the methods for
      examining Gasdermin-D cleavage by activated inflammatory caspases in vitro and
      upon inflammasome activation in vivo.

PMID- 29177861
TI  - Detection of ASC Speck Formation by Flow Cytometry and Chemical Cross-linking.
AB  - Assembly of a relatively large protein aggregate or "speck" formed by the adaptor
      protein ASC is a common downstream step in the activation of most inflammasomes.
      This unique feature of ASC allows its visualization by several imaging techniques
      and constitutes a reliable and feasible readout for inflammasome activation in
      cells and tissues. We have previously described step-by-step protocols to
      generate immortalized cell lines stably expressing ASC fused to a fluorescent
      protein for measuring inflammasome activation by confocal microscopy, and
      immunofluorescence of endogenous ASC in primary cells. Here, we present two more
      methods to detect ASC speck formation: (1) Assessment of ASC speck formation by
      flow cytometry; and (2) Chemical cross-linking of ASC followed by immunoblotting.
      These methods allow for the discrimination of inflammasome-activated versus non
      activated cells, the identification of lineage-specific inflammasome activation
      in complex cell mixtures, and sorting of inflammasome-activated cells for further
      analysis.

PMID- 29177862
TI  - Measuring Innate Immune Responses to Bacterial Viability.
AB  - The innate immune system directly senses microbial viability via the detection of
      a special class of viability-associated pathogen-associated molecular patterns
      (vita-PAMPs), such as prokaryotic messenger RNA. In the case of Gram-negative
      bacteria, detection of bacterial viability by phagocytes leads to a unique
      activation of inflammasome and type I interferon pathways, resulting in a robust
      pro-inflammatory innate response and a vigorous adaptive immune response. This
      protocol describes the methods required to study activation of both inflammasome
      and type I interferon pathways after stimulation of mouse bone marrow-derived
      macrophages with live or killed Gram-negative and Gram-positive bacteria. It
      covers the generation and handling of bone marrow-derived macrophages, the
      culture and killing of bacteria, the preparation of bacterial messenger RNA, and
      the stimulation of macrophages with live or killed bacteria. Lastly, this
      protocol describes the techniques employed to measure the hallmarks of
      inflammasome (secretion of interleukin-1beta) and type I interferon (activation
      of TBK1, IRF3 and secretion of type I interferon) pathways.

PMID- 29177863
TI  - Methods to Study Cell Swelling-Induced Inflammasome Activation.
AB  - Cells present ancestral conserved mechanisms to maintain their volume in response
      to alterations in environmental osmolarity. Changes in environmental osmolarities
      are therefore conserved as primitive stress signals. Innate immune cells, such as
      macrophages, express receptors to respond and shape immune response to stress,
      damage, or infection. The NLRP3 inflammasome is a multiprotein complex expressed
      in macrophages that senses pathogen- and danger-associated signals. The basic
      mechanisms of cell swelling and regulatory volume decrease are sensed by the
      NLRP3 inflammasome. Here, we present methods to study NLRP3 inflammasome
      activation in response to cell swelling.

PMID- 29177864
TI  - Detecting Release of Bacterial dsDNA into the Host Cytosol Using Fluorescence
      Microscopy.
AB  - Recognition of pathogens by the innate immune system relies on germline-encoded
      pattern recognition receptors (PRRs) that recognize unique microbial molecules,
      so-called pathogen-associated molecular patterns (PAMPs). Nucleic acids and their
      derivatives are one of the most important groups of PAMPs, and are recognized by
      a number of surface-associated as well as cytosolic PRRs. Cyclic GMP-AMP synthase
      (cGAS) recognizes the presence of pathogen- or host-derived dsDNA in the cytosol
      and initiates type-I-IFN production. Here, we describe a methodology that allows
      for evaluating the association of cGAS with released bacterial dsDNA during
      Francisella novicida infection of macrophages, by fluorescence confocal
      microscopy. This method can be adapted to the study of cGAS-dependent responses
      elicited by other intracellular bacterial pathogens and in other cell types.

PMID- 29177865
TI  - Quantitative Proteomics of Secreted Proteins.
AB  - Secreted proteins such as cytokines, interleukins, growth factors, and hormones
      have pleiotropic functions and facilitate intercellular communication in
      organisms. Quantification of these proteins conventionally relies on antibody
      based methods, i.e., enzyme-linked immunosorbent assays (ELISA), whose large
      scale use is limited by availability, specificity, and affordability.Here, we
      describe an experimental and bioinformatics workflow to comprehensively quantify
      cellular protein secretion by mass spectrometry. Secreted proteins are collected
      in vitro or ex vivo, digested with proteases and the resulting peptide mixtures
      are analyzed in single liquid chromatography-mass spectrometry (LC-MS/MS) runs.
      Label-free quantification and bioinformatics analysis is conducted in the
      MaxQuant and Perseus computational environment. Our workflow allows the
      quantification of thousands of secreted proteins spanning a concentration range
      of four orders of magnitude and permits the systems-level characterization of
      secretory programs as well as the discovery of proteins with unexpected
      extracellular functions.

PMID- 29177866
TI  - Simultaneous Detection of Cellular Viability and Interleukin-1beta Secretion from
      Single Cells by ELISpot.
AB  - Cell death results in the breakdown of the plasma membrane, which can cause the
      release of cytosolic proteins. During caspase-1-mediated cell death, termed
      pyroptosis, pro-inflammatory mediators that lack canonical secretory signal
      sequences, such as interleukin-1beta (IL-1beta), are released into the
      extracellular environment. To define whether cell death is required for the
      release of IL-1beta, or if IL-1beta can be actively secreted from viable cells,
      we have developed a modified IL-1beta Enzyme-Linked ImmunoSpot (ELISpot) assay.
      This assay simultaneously detects cellular viability and IL-1beta release at the
      single-cell level, and is therefore useful to examine how cell death influences
      IL-1beta secretion under different experimental conditions. Cells expressing a
      surrogate viability marker, such as GFP, are plated onto cellulose filter plates
      coated with an IL-1beta capture antibody. This antibody immobilizes IL-1beta as
      it is released from cells, allowing detection of distinct IL-1beta "spots." Both
      GFP positive cells and IL-1beta spots are detected and quantified using an AID
      ELISpot Reader, and the captured images are overlaid. Therefore, cell viability
      and IL-1beta release from individual cells can be monitored visually. We have
      recently used this method to document how individual fibroblasts expressing
      activated caspase-1 can secrete IL-1beta in the absence of cell death. Adaptation
      of this assay to other experimental conditions may help to define the
      circumstances where cell death influences IL-1beta release and IL-1beta-driven
      inflammatory responses.

PMID- 29177867
TI  - Detection and Quantification of MAVS Aggregation via Confocal Microscopy.
AB  - During infection, the cytosolic detection of viral double-stranded RNA (dsRNA)
      leads to the oligomerization and activation of mitochondrial antiviral signaling
      protein (MAVS) and the subsequent production of type I interferon (IFN). Here, we
      describe a novel method of visualizing and quantifying the aggregation of MAVS in
      response to dsRNA stimulation or viral infection in vitro using confocal
      microscopy.

PMID- 29177868
TI  - alpha-Methyl artoflavanocoumarin from Juniperus chinensis exerts anti-diabetic
      effects by inhibiting PTP1B and activating the PI3K/Akt signaling pathway in
      insulin-resistant HepG2 cells.
AB  - Diabetes mellitus is one of the greatest global health issues and much research
      effort continues to be directed toward identifying novel therapeutic agents.
      Insulin resistance is a challenging integrally related topic and molecules
      capable of overcoming it are of considerable therapeutic interest in the context
      of type 2 diabetes mellitus (T2DM). Protein tyrosine phosphatase 1B (PTP1B)
      negatively regulates insulin signaling transduction and is regarded a novel
      therapeutic target in T2DM. Here, we investigated the inhibitory effect of alpha
      methyl artoflavanocoumarin (MAFC), a natural flavanocoumarin isolated from
      Juniperus chinensis, on PTP1B in insulin-resistant HepG2 cells. MAFC was found to
      potently inhibit PTP1B with an IC50 of 25.27 +/- 0.14 uM, and a kinetics study
      revealed MAFC is a mixed type PTP1B inhibitor with a K i value of 13.84 uM.
      Molecular docking simulations demonstrated MAFC can bind to catalytic and
      allosteric sites of PTP1B. Furthermore, MAFC significantly increased glucose
      uptake and decreased the expression of PTP1B in insulin-resistant HepG2 cells,
      down-regulated the phosphorylation of insulin receptor substrate (IRS)-1
      (Ser307), and dose-dependently enhanced the protein levels of IRS-1,
      phosphorylated phosphoinositide 3-kinase (PI3K), Akt, and ERK1. These results
      suggest that MAFC from J. chinensis has therapeutic potential in T2DM by
      inhibiting PTP1B and activating insulin signaling pathways.

PMID- 29177869
TI  - Functional analysis of a regulator of G-protein signaling CgRGS1 in the rubber
      tree anthracnose fungus Colletotrichum gloeosporioides.
AB  - Colletotrichum gloeosporioides is the causal agent of rubber anthracnose, which
      is also one of the important biological factors threatening the development of
      natural rubber industry in the world. Regulators of G-protein signaling (RGS) are
      key negative regulators of G-proteins, which play important roles in growth,
      development and pathogenic processes of plant pathogens. In this study, a RGS
      gene CgRGS1 was functionally characterized in C. gloeosporioides. Compared to the
      wild type, the CgRGS1 deletion mutant had slow vegetative growth, reduced conidia
      with multi-end germination, low appressorium formation rate, high resistance to
      oxidative stress and SDS. Moreover, the mutant was sensitive to osmotic pressure
      and showed decreased virulence. In conclusion, CgRGS1 is involved in regulation
      of vegetative growth, conidiation, germination, appressorium formation, oxidative
      stress, osmotic pressure response and pathogenicity in C. gloeosporioides.

PMID- 29177871
TI  - Tumour functional sphericity from PET images: prognostic value in NSCLC and
      impact of delineation method.
AB  - PURPOSE: Sphericity has been proposed as a parameter for characterizing PET
      tumour volumes, with complementary prognostic value with respect to SUV and
      volume in both head and neck cancer and lung cancer. The objective of the present
      study was to investigate its dependency on tumour delineation and the resulting
      impact on its prognostic value. METHODS: Five segmentation methods were
      considered: two thresholds (40% and 50% of SUVmax), ant colony optimization,
      fuzzy locally adaptive Bayesian (FLAB), and gradient-aided region-based active
      contour. The accuracy of each method in extracting sphericity was evaluated using
      a dataset of 176 simulated, phantom and clinical PET images of tumours with
      associated ground truth. The prognostic value of sphericity and its complementary
      value with respect to volume for each segmentation method was evaluated in a
      cohort of 87 patients with stage II/III lung cancer. RESULTS: Volume and
      associated sphericity values were dependent on the segmentation method. The
      correlation between segmentation accuracy and sphericity error was moderate
      (|rho| from 0.24 to 0.57). The accuracy in measuring sphericity was not dependent
      on volume (|rho| < 0.4). In the patients with lung cancer, sphericity had
      prognostic value, although lower than that of volume, except for that derived
      using FLAB for which when combined with volume showed a small improvement over
      volume alone (hazard ratio 2.67, compared with 2.5). Substantial differences in
      patient prognosis stratification were observed depending on the segmentation
      method used. CONCLUSION: Tumour functional sphericity was found to be dependent
      on the segmentation method, although the accuracy in retrieving the true
      sphericity was not dependent on tumour volume. In addition, even accurate
      segmentation can lead to an inaccurate sphericity value, and vice versa.
      Sphericity had similar or lower prognostic value than volume alone in the
      patients with lung cancer, except when determined using the FLAB method for which
      there was a small improvement in stratification when the parameters were
      combined.

PMID- 29177870
TI  - Dosimetric parameters predicting contralateral liver hypertrophy after unilobar
      radioembolization of hepatocellular carcinoma.
AB  - PURPOSE: This study aimed at identifying prior therapy dosimetric parameters
      using 99mTc-labeled macro-aggregates of albumin (MAA) that are associated with
      contralateral hepatic hypertrophy occurring after unilobar radioembolization of
      hepatocellular carcinoma (HCC) performed with 90Y-loaded glass microspheres.
      METHODS: The dosimetry data of 73 HCC patients were collected prior to the
      treatment with 90Y-loaded microspheres for unilateral disease. The injected liver
      dose (ILD), the tumor dose (TD) and healthy injected liver dose (HILD) were
      calculated based on MAA quantification. Following treatment, the maximal
      hypertrophy (MHT) of an untreated lobe was calculated. RESULTS: Mean MHT was 35.4
      +/- 40.4%. When using continuous variables, the MHT was not correlated with any
      tested variable, i.e., injected activity, ILD, HILD or TD except with a
      percentage of future remnant liver (FRL) following the 90Y-microspheres injection
      (r = -0.56). MHT >= 10% was significantly more frequent for patients with HILD
      >= 88 Gy, (52% of the cases), i.e., in 92.2% versus 65.7% for HILD < 88 Gy (p =
      0.032). MHT >= 10% was also significantly more frequent for patients with a TD >=
      205 Gy and a tumor volume (VT) >= 100 cm3 in patients with initial FRL < 50%. MHT
      >=10% was seen in 83.9% for patients with either an HILD >= 88 Gy or a TD >= 205
      Gy for tumors larger than 100cm3 (85% of the cases), versus only 54.5% (p =
      0.0265) for patients with none of those parameters. MHT >=10% was also associated
      with FRL and the Child-Pugh score. Using multivariate analysis, the Child-Pugh
      score (p < 0.0001), FRL (p = 0.0023) and HILD (p = 0.0029) were still
      significantly associated with MHT >=10%. CONCLUSION: This study demonstrates for
      the first time that HILD is significantly associated with liver hypertrophy.
      There is also an impact of high tumor doses in large lesions in one subgroup of
      patients. Larger prospective studies evaluating the MAA dosimetric parameters
      have to be conducted to confirm these promising results.

PMID- 29177872
TI  - Morphological Evaluation of the Influence of the Peptide Complex from Tissue of
      Porcine Kidneys on the Experimental Urolithiasis.
AB  - We performed morphological analysis of the effect of the peptide complex from
      porcine kidneys on the course of experimental urolithiasis modeled in rats by
      treatment with 1% ethylene glycol solution (in drinking water) for 6 weeks. The
      peptide complex obtained by acetic acid extraction was administered in a dose of
      15 mg. Administration of the peptide complex to animals with experimental kidney
      stone disease leads to 100% destruction of large and medium stones to the "dust"
      granularity.

PMID- 29177874
TI  - The Role of the Glutathione System in Oxidative Modification of Proteins and
      Dysregulation of Apoptosis in Jurkat Tumor Cells.
AB  - We compared changes in the redox status and intensity of oxidative modification
      of proteins in intact Jurkat tumor cells and cells cultured with buthionine
      sulfoximine, an inhibitor of the key enzyme of glutathione synthesis gamma
      glutamylcysteine synthetase. The glutathione system components play a role in
      modulation of the content of protein-bound glutathione, protein carbonyl
      derivatives, bityrosine, and oxidized tryptophan, and in dysregulation of
      apoptosis in Jurkat tumor cells. Inhibition of de novo synthesis of glutathione
      in Jurkat tumor cells was followed by accumulation of hydroxyl radical, a
      reduction in the level of protein-bound glutathione and oxidized tryptophan, and
      a rise in the concentration of protein carbonyl derivatives. These changes were
      accompanied by activation of programmed cell death.

PMID- 29177873
TI  - Biodistribution of Alpha-Fetoprotein-Containing Noncovalent Complex Aimpila with
      Antitumor Activity.
AB  - Biodistribution of [125I]Aimpila (20 mg/kg) in the tumor and normal tissues,
      including the mammary gland tissue, after single oral dose was studied in BALB/c
      nude mice with T47D/ReCAF+++ human breast tumor sensitive to this drug and in
      closely related BALB/c nude+mice without tumors. The maximum concentration of
      [125I]Aimpila was in fact the same in the tumor and in the mammary gland, while
      the time course of its accumulation/elimination differed. The time of the maximum
      accumulation of the drug in the tumor was shorter and its persistence longer than
      in normal tissue. After 24 h, label concentration in the tumor was 4.5 times
      higher (p=0.002). Differences in the time course of label accumulation in the
      tumor were detected. The maximum ratio of tumor/blood concentrations of the
      preparation was recorded in 1 h after administration. [125I]Aimpila and
      [125I]alpha-fetoprotein accumulated in the tumor in comparable concentrations and
      were eliminated simultaneously at the same rate. The results of comparative
      analysis of accumulation of the labeled compounds in Aimpila-sensitive
      T47D/RECAF+++ tumor from 0.5 to 9.0 h after drug administration could be
      interpreted as a result of possible receptor-mediated binding of the complex with
      the tumor at the expense of the alpha-fetoprotein transporting part. Differences
      in the parameters of [125I]Aimpila biodistribution in the tumor and normal
      mammary tissue indirectly attested to selective antiproliferative activity of the
      complex.

PMID- 29177875
TI  - Peculiarities of Cell Seeding on Polylactic Acid-Based Scaffolds Fabricated Using
      Electrospinning and Solution Blow Spinning Technologies.
AB  - We studied the possibility of seeding bone marrow-derived stromal cells onto
      polylactic acid-based scaffolds fabricated by electrospinning and solution blow
      spinning technologies. The cells were applied to the scaffolds by dynamic seeding
      and scaffolds were then cultured in Petri dishes in culture medium for 3 days.
      Cell migration to the Petri dish surface was noted only for scaffolds fabricated
      by electrospinning technology, but DAPI staining confirmed the presence of cells
      in both scaffolds. The mean number of cells in scaffolds fabricated by
      electrospinning and solution blow spinning was 56+/-9 and 81+/-6, respectively.
      The scaffold fabricated by solution blow spinning was more effectively (p<0.05)
      colonized by cells due to its more optimal spatial structure.

PMID- 29177876
TI  - Bioluminescent Study of the Distribution of High-Molecular-Weight Protein
      Fraction of Cellex Daily Preparation in the Brain after Intranasal Administation.
AB  - Permeability of the blood-brain barrier for protein fractions 50-100 kDa (PF50
      100) of Cellex Daily preparation labeled with fluorescent tracer FITC and non
      conjugated FITC were compared after intranasal administration of the preparations
      to healthy rats. Fluorimetrical analysis of the serum and cerebrospinal fluid
      samples showed that Cellex Daily PF50-100-FITC administered intranasally
      penetrated into the blood and cerebrospinal fluid with maximum accumulation in 2
      h after administration and persists in the circulation for 24 h probably due to
      binding with plasma proteins. The differences in the kinetic profile of PF50-100
      FITC and free FITC indirectly suggest that the major part of the preparation is
      not degraded within 24 h and FITC is probably not cleaved from the protein
      components of the preparation. In vivo fluorescence analysis showed significant
      fluorescent signal in the olfactory bulbs in 6 h after intranasal administration;
      hence, the preparation administered via this route can bypass the blood-brain
      barrier. Scanning laser confocal microscopy of rat brain sections confirmed
      penetration of the high-molecular weight protein fraction PF50-100-FITC into CNS
      structures. The most pronounced accumulation of the labeled drug was observed in
      the olfactory bulb in 6 and 12 h after administration. In contrast to free FITC
      administered in the control group, significant accumulation of PF50-100-FITC in
      the olfactory cortex and frontal cortex neurons with functionally active nuclei
      was observed in 6, 12 and 24 h after intranasal administration.

PMID- 29177877
TI  - Application of Preparations Containing Copper Nanoparticles for the Treatment of
      Experimental Septic Wounds.
AB  - Regenerative activity of locally applied drugs based on copper nanoparticles was
      compared on white male rats with an experimental purulent wound infected with
      clinical polyantibiotic resistant strains of Staphylococcus aureus. The use of a
      suspension of copper nanoparticles and complex drugs based on chitosan and starch
      with copper nanoparticles led to a rapid reduction of the wound area and
      elimination of the wound-contaminating agent, which confirmed high antibacterial
      and regenerative activity of copper nanoparticles in the composition of the
      studied drugs.

PMID- 29177878
TI  - Anterior Mediastinal Lymph Nodes in Chemically Induced Breast Cancer.
AB  - The anterior mediastinal lymph nodes were analyzed morphometrically in rats with
      chemically provoked breast cancer. Rats with untreated breast cancer and animals
      receiving chemotherapy demonstrated decreased volumes of paracortical region and
      lymphoid nodules with the germinal centers accompanied by extended medullary
      thymic substance. Resection of largest focus of breast tumor improved the
      filtration barrier potential of anterior mediastinal lymph nodes, up-regulated
      the proliferative activity of lymphoid cells in T-cell zones, and down-regulated
      proliferation of plasmatic cells.

PMID- 29177879
TI  - Structural Dynamics of Chondrocytes during Culturing.
AB  - We performed comparative analysis of the morphology of chondrocytes in normal
      cartilage, after their isolation from the tissue, and at different stages of
      culturing; structural dynamics of cells during culturing was also studied.
      Significant morphological differences in chondrocytes at the specified stages of
      their preparation to in vivo use were revealed. Pronounced structural changes
      (blebbing and cytoplasm swelling) were found in chondrocytes before their
      implantation, which can affect the formation of cartilage regenerate. The study
      was performed using light microscopy methods including time-lapse recording of
      the cell cultures with differential interference Nomarski contrasting combined
      with transmission electron microscopy.

PMID- 29177880
TI  - Regeneration Potential of Lymphoid Tissue of Small Intestine in Mice after
      Exposure to Low-Intensity Radiation.
AB  - Number and size of aggregated lymphoid nodules in the small intestine of mice
      exposed to radiation using a gamma-irradiation unit GOBO-60 with 137Cs source
      were measured using the methods of visual microscopy and morphometry.
      Morphological status of the nodules was estimated on days 4, 28, 60, and 90 after
      the exposure. Significant changes were observed in the lymphoid system of the
      small intestine after exposure to low-intensity radiation. The size of aggregated
      lymphoid nodules decreased and the relative number of cells with degenerative
      changes increased. Regenerative processes were observed as soon as on day 4 of
      the rehabilitation period. However, the number and sizes of aggregated lymphoid
      nodules (length, width, and section area), and the ratio of lymphoid nodules with
      germinal center were still lower than in the control. The number of cells forming
      lymphoid interstitial plaques was close to the control on days 28-90 of the
      rehabilitation process.

PMID- 29177881
TI  - Ultrastructure of Rat Kidneys after Intravenous Administration of Modified
      Magnetite Nanoparticles.
AB  - The ultrastructure of nephrocytes of the proximal and distal convoluted tubules,
      podocytes, mesangial cells, and macrophages of the interstitial connective tissue
      was studied after single intravenous administration of magnetite nanoparticles
      modified with chitosan (magnetic nanospheres) or lipids (magnetic liposomes).
      Transmission electron microscopy showed ultrastructural features of absorption of
      magnetite nanoparticles. The shape, size, and number of vesicles containing
      nanoparticles in nephrocytes of convoluted tubules and macrophages after
      administration of the suspensions of magnetic nanospheres and magnetic liposomes
      were described.

PMID- 29177882
TI  - Effect of the Natural Cytokine Complex on the Structure and Metabolism of
      Contractile Myocardium Normally and under Increased Hemodynamic Load.
AB  - Effect of natural complex of cytokines with activity of IL-1, IL-2, IL-6, TNF,
      MIF, GTFbeta on the structure and metabolism of contractile ventricular
      cardiomyocytes was assessed in the control and under conditions of acute
      experimental aortic stenosis. Systemic administration of the complex in the
      control had no significant effect on myocardial morphology with low number of
      damaged cardiomyocytes and low degree of structural damage. Administration of the
      cytokine complex against the background of aortic stenosis did not exert any
      additional alterative effect on cardiomyocytes, structural damage of contractual
      nature was moderate. Systemic administration of the natural cytokine complex had
      a pronounced inhibitory effect on metabolic processes in the myocardium of both
      ventricles both in the control and against the background of increased
      hemodynamic load. In cardiomyocytes, glycolysis and citric acid cycle were slowed
      down, oxidation of free fatty acids and their metabolic products was inhibited as
      well as shuttle mechanisms and biosynthetic reactions. Inhibition of energy
      producing processes is the cause of the lack of the contractile function energy
      supply and can worsen the course of cardiovascular diseases and increase the risk
      of their complications in conditions, accompanied by increased blood cytokine
      level.

PMID- 29177883
TI  - Non-Competitive NMDA Receptor Antagonist Hemantane Reduces Ethanol Consumption in
      Long-Term Alcohol Experienced Rats.
AB  - Activity of hemantane, an amino adamantane derivative, exhibiting the properties
      of lowaffinity non-competitive NMDA receptor antagonist, was evaluated in
      experimental in vivo models of alcoholism. Hemantane had no effects on the
      formation and manifestation of behavioral sensitization to ethanol in DBA/2 mice.
      Under conditions of free choice between 10% ethanol and water, hemantane (20
      mg/kg/day for 14 days, intraperitoneally) significantly reduced the daily ethanol
      intake in random-bred male rats with formed alcohol motivation (>4 g/kg of
      ethanol). During modelling of withdrawal syndrome, hemantane administered
      intraperitoneally in doses of 5-20 mg/kg dose-dependently attenuated alcohol
      deprivation effect after acute withdrawal with no effects on protracted
      abstinence. It was found that hemantane suppressed alcohol drinking behavior in
      long-term ethanol experienced rats and attenuated alcohol-seeking behavior after
      acute withdrawal.

PMID- 29177884
TI  - Oxidative Stress as a Mechanisms of Reduced Glucose Absorption under Conditions
      of Immobilization Stress.
AB  - Experimental studies demonstrated inhibition of glucose absorption in the jejunum
      in acute and chronic 1-h daily immobilization stress, with the maximum inhibition
      on day 7 of immobilization. These changes correlate with the development of
      oxidative stress in animals over the entire duration of the experiment, which
      manifested by an increase in the content of the primary and end LPO products and
      decrease of the total antioxidant activity of the blood. Correction of these
      shifts with the antioxidant drug inhibits accumulation of LPO products and
      increases antioxidant defense and glucose absorption rate. These data prove the
      important role of peroxidation in regulation of glucose absorption.

PMID- 29177886
TI  - Production of poly-gamma-glutamic acid by a thermotolerant glutamate-independent
      strain and comparative analysis of the glutamate dependent difference.
AB  - Poly-gamma-glutamic acid (gamma-PGA) is a promising microbial polymer with wide
      applications in industry, agriculture and medicine. In this study, a novel
      glutamate-independent gamma-PGA producing strain with thermotolerant
      characteristics was isolated and identified as Bacillus subtilis GXG-5, then its
      product was also characterized. The fermentation process was optimized by single
      factor tests, and results showed that high temperature (50  degrees C) was
      especially suitable for the gamma-PGA production by GXG-5. The gamma-PGA yield
      reached 19.50 +/- 0.75 g/L with substrate conversion efficiency of 78% at 50 
      degrees C in 10 L fermentor. Comparison of GXG-5 and GXA-28 (glutamate-dependent
      strain) under respective optimal fermentation conditions, the gamma-PGA yield of
      GXG-5 was 19.0% higher than that of GXA-28, and GXG-5 was also superior to GXA-28
      in the availability of carbon sources and substrates. Furthermore, the glutamate
      dependent difference between GXA-28 and GXG-5 was analyzed by genomic sequencing,
      results indicated that genes related to the glutamate dependent difference mainly
      involved in carbohydrate transport and metabolism and amino acid metabolism, and
      13 genes related to gamma-PGA synthesis were mutated in GXG-5. This study
      provided a potential glutamate-independent strain to replace glutamate-dependent
      strain for gamma-PGA production, and shared novel information for understanding
      the glutamate dependent difference at the genomic level.

PMID- 29177885
TI  - Clopidogrel Therapy in Patients with Cardiovascular Disease Undergoing
      Transurethral Resection of the Prostate: A Step Towards Individualization.
AB  - OBJECTIVES: The objective of this study was to test platelet function pre- and
      peri-operatively in clopidogrel-treated patients undergoing transurethral
      resection of the prostate. METHODS: This was a pilot study involving 20 male
      patients treated with clopidogrel (75 mg/day) for the secondary prevention of
      cardiovascular disease and scheduled for elective transurethral resection of the
      prostate. Platelet function testing with light transmittance aggregometry in
      platelet-rich plasma of four samples (T0, T1, T2, and T3 drawn on the same day, 3
      and 7 days of clopidogrel cessation and 24-h post-operatively, respectively) was
      performed and evaluated in each patient. P-selectin membrane expression was
      evaluated using monoclonal antibodies. RESULTS: The platelet response to
      adenosine diphosphate 5 uMU and 20 uMU at T0 were 42 +/- 15 and 60 +/- 14%,
      respectively. After discontinuation of clopidogrel, corresponding maximum
      aggregation values at T1 were 60 +/- 16 and 74 +/- 14%, and increased to 69 +/-
      16 and 79 +/- 18% at T2. No significant difference in platelet aggregation values
      were noted between T1 and T2, while similar aggregation values were recorded at
      T3. CONCLUSIONS: Our findings indicate that in patients undergoing transurethral
      resection of the prostate, platelet activation is similar 3 and 7 days from
      clopidogrel cessation. These results may be of relevance in subjects at increased
      thrombotic risk prior to a surgical procedure carrying a high-bleeding risk.

PMID- 29177887
TI  - FreB is involved in the ferric metabolism and multiple pathogenicity-related
      traits of Verticillium dahliae.
AB  - Ferric reductases are integral membrane proteins involved in the reduction of
      environmental ferric iron into the biologically available ferrous iron. In the
      most overwhelming phytopathogenic fungus, Verticillium dahliae, these ferric
      reductase are not studied in details. In this study we explored the role of FreB
      gene (VDAG_06616) in the ferric reduction and virulence of V. dahliae by
      generating the knockout mutants (DeltaFreB) and complementary strains (DeltaFreB
      C) using protoplast transformation. When cultured on media supplemented with
      FeSO4, FeCl3 and no iron, DeltaFreB exhibited significantly reduced growth and
      spore production especially on media with no iron. Transmembrane ferric reductase
      activity of DeltaFreB was decreased up to 50% than wild type strains (Vd-wt). The
      activity was fully restored in DeltaFreB-C. Meanwhile, the expression levels of
      other related genes (Frect-4, Frect-5, Frect-6 and Met) were obviously increased
      in DeltaFreB. Compared with the Vd-wt and DeltaFreB-C, DeltaFreB-1 and DeltaFreB
      2 were impaired in colony diameter and spore number on different carbon sources
      (starch, sucrose, galactose and xylose). DeltaFreB-1 and DeltaFreB-2 were also
      highly sensitive to oxidative stress as revealed by the plate diffusion assay
      when 100 uM H2O2 was applied to the fungal culture. When Nicotiana benthamiana
      plants were inoculated, DeltaFreB exhibited less disease symptoms than Vd-wt and
      DeltaFreB-C. In conclusion, the present findings not only indicate that FreB
      mediates the ferric metabolism and is required for the full virulence in V.
      dahliae, but would also accelerate future investigation to uncover the pathogenic
      mechanism of this fungus.

PMID- 29177889
TI  - Reply to the letter to the editor regarding our article "Preoperative magnetic
      resonance imaging predicts eligibility for arthroscopic primary anterior cruciate
      ligament repair".

PMID- 29177888
TI  - Benchmark dose analyses of multiple genetic toxicity endpoints permit robust,
      cross-tissue comparisons of MutaMouse responses to orally delivered
      benzo[a]pyrene.
AB  - Genetic damage is a key event in tumorigenesis, and chemically induced genotoxic
      effects are a human health concern. Although genetic toxicity data have
      historically been interpreted using a qualitative screen-and-bin approach, there
      is increasing interest in quantitative analysis of genetic toxicity dose-response
      data. We demonstrate an emerging use of the benchmark dose (BMD)-approach for
      empirically ranking cross-tissue sensitivity. Using a model environmental
      carcinogen, we quantitatively examined responses for four genetic damage
      endpoints over an extended dose range, and conducted cross-tissue sensitivity
      rankings using BMD100 values and their 90% confidence intervals (CIs). MutaMouse
      specimens were orally exposed to 11 doses of benzo[a]pyrene. DNA adduct frequency
      and lacZ mutant frequency (MF) were measured in up to 8 tissues, and Pig-a MF and
      micronuclei (MN) were assessed in immature (RETs) and mature red blood cells
      (RBCs). The cross-tissue BMD pattern for lacZ MF is similar to that observed for
      DNA adducts, and is consistent with an oral route-of-exposure and differences in
      tissue-specific metabolism and proliferation. The lacZ MF BMDs were significantly
      correlated with the tissue-matched adduct BMDs, demonstrating a consistent adduct
      conversion rate across tissues. The BMD CIs, for both the Pig-a and the MN
      endpoints, overlapped for RETs and RBCs, suggesting comparable utility of both
      cell populations for protracted exposures. Examination of endpoint-specific
      response maxima illustrates the difficulty of comparing BMD values for a fixed
      benchmark response across endpoints. Overall, the BMD-approach permitted robust
      comparisons of responses across tissues/endpoints, which is valuable to our
      mechanistic understanding of how benzo[a]pyrene induces genetic damage.

PMID- 29177890
TI  - AREDS simplified severity scale as a predictive factor for response to
      aflibercept therapy for typical neovascular age-related macular degeneration.
AB  - PURPOSE: To investigate whether the severity of the condition in the untreated
      fellow eye is a predictive factor for the response to intravitreal aflibercept
      injection (IAI) for exudative age-related macular degeneration (AMD). METHODS: A
      retrospective medical chart review was conducted for 88 patients with treatment
      naive neovascular AMD, who were initially treated with three monthly IAIs,
      followed by monthly monitoring and re-injection as needed for at least 12 months.
      Subjects were classified into three groups according to the severity of the
      condition in their untreated eye, based on the severity scale in the Age-Related
      Eye Disease Study (AREDS): group 0, AREDS severity level 1 (no drusen); group 1,
      AREDS severity level 2 or 3 (any drusen); group 2, AREDS severity level 4
      (advanced AMD). Genotyping was performed in all cases for ARMS2 A69S and CFH
      I62V. RESULTS: Fellow-eye severity was associated with age and the risk variant
      of ARMS2 A69S (P = 0.005 and 0.001, respectively). Although best-corrected visual
      acuity (BCVA) had improved significantly after 12 months in all groups, this
      improvement was significantly greater in group 0 than in the other groups (P =
      0.008). The retreatment-free period was also significantly longer for group 0
      than for the other groups (P = 0.016), and the number of additional injections
      was significantly associated with fellow-eye severity (P = 0.007). CONCLUSIONS:
      Fellow-eye severity was associated with treatment response in terms of visual
      improvement and retreatment and may be a predictive factor for response to IAI
      for neovascular AMD.

PMID- 29177892
TI  - Exploring the genetics of fertility restoration controlled by Rf1 in common wheat
      (Triticum aestivum L.) using high-density linkage maps.
AB  - Hybrid wheat breeding has the potential to significantly increase wheat
      productivity compared to line breeding. The induction of male sterility by the
      cytoplasm of Triticum timopheevii Zhuk. is a widely discussed approach to ensure
      cross-pollination between parental inbred lines in hybrid wheat seed production.
      As fertility restoration in hybrids with this cytoplasm is often incomplete,
      understanding the underlying genetics is a prerequisite to apply this technology.
      A promising component for fertility restoration is the restorer locus Rf1, which
      was first detected on chromosome 1A of the restorer accession R3. In the present
      study, we performed quantitative trait locus (QTL) analyses to locate Rf1 and
      estimate its effect in populations involving the restorer lines R3, R113 and L19.
      Molecular markers linked to Rf1 in these populations were used to analyse the
      genomic target region in T. timopheevii accessions and common wheat breeding
      lines. The QTL analyses revealed that Rf1 interacted with a modifier locus on
      chromosome 1BS and the restorer locus Rf4 on chromosome 6B. The modifier locus
      significantly influenced both the penetrance and expressivity of Rf1. Whereas Rf1
      exhibited expressivity higher than that of Rf4, the effects of these loci were
      not additive. Evaluating the marker haplotype for the Rf1 region, we propose that
      the restoring Rf1 allele may be derived exclusively from T. timopheevii. The
      present study demonstrates that interactions between restorer and modifier loci
      play a critical role in fertility restoration of common wheat with the cytoplasm
      of T. timopheevii.

PMID- 29177891
TI  - Plasma levels of hypoxia-regulated factors in patients with age-related macular
      degeneration.
AB  - PURPOSE: Various hypoxia-related proteins are differentially expressed in the
      retina and secreted to the vitreous and/or aqueous humor of patients affected by
      dry or neovascular age-related macular degeneration (nAMD). To determine whether
      these conditions alter concentrations of cytokines also in the systemic
      circulation, we measured plasma levels of six hypoxia-related proteins. METHODS:
      Plasma was prepared from EDTA blood that was collected from patients affected by
      dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9),
      and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as
      negative controls, PDR samples as positive controls. Protein concentrations of
      vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin
      like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha
      (TNF-alpha), and pigment epithelium-derived factor (PEDF) were determined by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of PlGF was
      significantly increased in plasma of patients affected by nAMD. Although no
      statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF
      alpha, and PEDF, the mean concentration of VEGF was lowest in the nAMD group.
      Plasma concentrations of the six factors did not correlate with gender or age of
      patients. CONCLUSIONS: nAMD may increase plasma concentrations of PlGF, making it
      a candidate as a biomarker for the neovascular form of AMD. Other factors,
      however, were not differentially regulated, suggesting that their systemic
      concentrations are not generally increased in hypoxia-related retinal diseases.

PMID- 29177893
TI  - Cardiac involvement in eosinophilic granulomatosis with polyangiitis.

PMID- 29177894
TI  - Understanding the Factors that Influence Perceptions of Post-Wildfire Landscape
      Recovery Across 25 Wildfires in the Northwestern United States.
AB  - Disturbances such as wildfire are important features of forested landscapes. The
      trajectory of changes following wildfires (often referred to as landscape
      recovery) continues to be an important research topic among ecologists and
      wildfire scientists. However, the landscape recovery process also has important
      social dimensions that may or may not correspond to ecological or biophysical
      perspectives. Perceptions of landscape recovery may affect people's attitudes and
      behaviors related to forest and wildfire management. We explored the variables
      that influence people's perceptions of landscape recovery across 25 fires that
      occurred in 2011 or 2012 in the United States of Washington, Oregon, Idaho, and
      Montana and that represented a range of fire behavior characteristics and
      landscape impacts. Residents near each of the 25 fires were randomly selected to
      receive questionnaires about their experiences with the nearby fire, including
      perceived impacts and how the landscape had recovered since the fire. People
      generally perceived landscapes as recovering, even though only one to two years
      had passed. Regression analysis suggested that perceptions of landscape recovery
      were positively related to stronger beliefs about the ecological role of fire and
      negatively related to loss of landscape attachment, concern about erosion,
      increasing distance from the fire perimeter, and longer lasting fires.
      Hierarchical linear modeling (HLM) analysis indicated that the above
      relationships were largely consistent across fires. These findings highlight that
      perceptions of post-fire landscape recovery are influenced by more than
      vegetation changes and include emotional and cognitive factors. We discuss the
      management implications of these findings.

PMID- 29177895
TI  - Biopsy diagnosis of colitis: an algorithmic approach.
AB  - Certain types of colitides, such as collagenous colitis, lymphocytic colitis, and
      ischemic colitis, have distinct histologic features that allow for a specific
      diagnosis. However, in most colonic biopsy specimens, a definite diagnosis cannot
      be established on the basis of histology alone. Thus, in most cases of colitis,
      it is helpful to utilize a systematic approach in order to recognize patterns of
      injury. This information in conjunction with clinical and laboratory findings may
      help pathologists narrow the differential diagnosis and/or establish a more
      definite etiology for the patient's illness in order to guide clinical
      management. We provide general guidelines to distinguish variations in normal
      mucosa and biopsy procedure-related artifacts from true inflammatory conditions.
      Inflammatory conditions may be further categorized into those with predominantly
      lymphoplasmacytic inflammation (with or without neutrophils), predominantly
      neutrophilic inflammation, predominantly eosinophilic inflammation, or
      paucicellular colitis, since each of these patterns of inflammation are
      associated with a distinct differential diagnosis. This review will focus on a
      pattern-based algorithmic approach to evaluating biopsies of patients who present
      to physicians with signs and symptoms of colitis.

PMID- 29177896
TI  - Author Correction: Volatiles Emitted by Calling Males of Burying Beetles and
      Ptomascopus morio (Coleoptera: Silphidae: Nicrophorinae) Are Biogenetically
      Related.
AB  - The original version of this article unfortunately contained a mistake. The name
      of the main component released by Nicrophorus defodiens in Fig. 1a should read
      "Fuscumyl acetate", not "Fuscumol".

PMID- 29177897
TI  - Attraction of Three Mirid Predators to Tomato Infested by Both the Tomato Leaf
      Mining Moth Tuta absoluta and the Whitefly Bemisia tabaci.
AB  - Plants emit volatile compounds in response to insect herbivory, which may play
      multiple roles as defensive compounds and mediators of interactions with other
      plants, microorganisms and animals. Herbivore-induced plant volatiles (HIPVs) may
      act as indirect plant defenses by attracting natural enemies of the attacking
      herbivore. We report here the first evidence of the attraction of three
      Neotropical mirid predators (Macrolophus basicornis, Engytatus varians and
      Campyloneuropsis infumatus) toward plants emitting volatiles induced upon feeding
      by two tomato pests, the leaf miner Tuta absoluta and the phloem feeder Bemisia
      tabaci, in olfactometer bioassays. Subsequently, we compared the composition of
      volatile blends emitted by insect-infested tomato plants by collecting headspace
      samples and analyzing them with GC-FID and GC-MS. Egg deposition by T. absoluta
      did not make tomato plants more attractive to the mirid predators than uninfested
      tomato plants. Macrolophus basicornis is attracted to tomato plants infested with
      either T. absoluta larvae or by a mixture of B. tabaci eggs, nymphs and adults.
      Engytatus varians and C. infumatus responded to volatile blends released by
      tomato plants infested with T. absoluta larvae over uninfested plants. Also,
      multiple herbivory by T. absoluta and B. tabaci did not increase the attraction
      of the mirids compared to infestation with T. absoluta alone. Terpenoids
      represented the most important class of compounds in the volatile blends and
      there were significant differences between the volatile blends emitted by tomato
      plants in response to attack by T. absoluta, B. tabaci, or by both insects. We,
      therefore, conclude that all three mirids use tomato plant volatiles to find T.
      absoluta larvae. Multiple herbivory did neither increase, nor decrease attraction
      of C. infumatus, E. varians and M. basicornis. By breeding for higher rates of
      emission of selected terpenes, increased attractiveness of tomato plants to
      natural enemies may improve the effectiveness of biological control.

PMID- 29177898
TI  - Adaptation of Defensive Strategies by the Pea Aphid Mediates Predation Risk from
      the Predatory Lady Beetle.
AB  - Within a species, individual animals adopt various defensive strategies to resist
      natural enemies, but the defensive strategies that are adopted in response to
      variations in predation risk are poorly understood. Here, we assessed consecutive
      foraging processes on cohorts of two biotypes (green and red) of the pea aphid,
      Acyrthosiphon pisum, by the predatory lady beetle Propylea japonica, to
      investigate the adaptive mechanism underlying the defensive strategy. We observed
      the behavioral responses of individuals (continue feeding or escape, i.e., walk
      away or drop off from initial feeding site), simultaneously quantified the amount
      of alarm pheromone, (E)-beta-farnesene (EbetaF) released from cohorts using gas
      chromatography-mass spectrometry (GC-MS), and recorded the foraging times of
      predators in intervals. The results indicated that: (1) the anti-predator
      responses differed markedly between biotypes and among the stages of the
      consecutive foraging processes. (2) Few green cohorts tended to release EbetaF
      during the first foraging; those that did released only a low dose that did not
      increase the number of escapes. However, the amount of EbetaF rose rapidly
      following the second foraging process, which caused an intense escape response.
      In contrast, more red cohorts released greater amounts of EbetaF, which caused
      more individuals to escape from their innate feeding sites during the first
      foraging. During the second foraging, more red individuals tended to escape
      without releasing EbetaF in greater quantities. (3) The foraging time was
      effectively shortened in each biotype cohort that adopted diverse defensive
      strategies. This study of the defensive strategies of the pea aphid may
      contribute to understanding the intraspecific differences in aphid defense
      mechanisms.

PMID- 29177899
TI  - Neuroprotective Effect of sigma1-Receptors on the Cell Model of Huntington's
      Disease.
AB  - Huntington's disease is a hereditary neurodegenerative disease that primarily
      affects striatal neurons. Recent studies demonstrated abnormalities in calcium
      regulation in striatal neurons in Huntington's disease, which leads to
      elimination of synaptic connections between cortical and striatal neurons. In the
      present study, we focused on the neuroprotective properties of sigma1-receptor,
      because one of its main functions is associated with modulation of calcium
      homeostasis in cells. The application of selective sigma1-receptor agonists to
      the corticostriatal cell culture restores synaptic connections between the
      cortical and striatal neurons. Based on the obtained data, we assume that sigma1
      receptor is a promising target for the development of drugs for the therapy of
      Huntington's disease.

PMID- 29177900
TI  - Focal Unilateral Traumatic brain injury Causes Delayed Neurodegenerative Changes
      in the Brain of Rats.
AB  - A cascade of pathological changes in the intact hemisphere developed in rats 6
      months after focal unilateral traumatic brain injury: neuronal degeneration,
      hyperexpression of alpha-synuclein, APP (beta-amyloid peptide precursor) protein,
      and glutamine synthetase in cells other than astrocytes. The development of these
      changes in the contralateral hemisphere indicated the emergence of extensive
      delayed neurodegenerative processes in the brain after traumatic brain injury,
      which were characteristic of diseases associated with pathological aging.

PMID- 29177901
TI  - Morphofunctional Properties of Human Platelets Treated with Silver Nanoparticles.
AB  - We studied structural and functional properties of human platelets in the
      presence of nanosilver particles. Incubation with 0.05-5 MUM silver nanoparticles
      suppressed platelet adhesion in a dose-dependent manner without affecting
      internal platelet structure; during adhesion, some granules were not exocytized.
      Spontaneous platelet activation was observed at nanoparticle concentrations 15
      100 MUM. Addition of 1-5 MUM nanosilver to cells undergoing adhesion blocked
      massive platelet degranulation, but did not prevent the formation of
      lamellopodia. The maximum number of preserved granules in platelets was revealed
      in the presence of 2.5-5 MUM silver nanoparticles: 50% after platelet
      preincubation with silver nanoparticles and 75-77% after stabilization of
      adherent platelets with silver nanoparticles.

PMID- 29177902
TI  - Effect of Native and Modified Apolipoprotein A-I on DNA Synthesis in Cultures of
      Different Cells.
AB  - Culturing of bone marrow cells in serum-free RPMI-1640 medium for 24 h was
      accompanied by a decrease in the rate of [3H]-thymidine incorporation into DNA.
      Addition of native apolipoprotein A-I (apoA-I) or plasma LDL and HDL to the
      culture medium increased this parameter. In contrast to native apoA-I, its
      modified form decelerated DNA synthesis in bone marrow cells. A similar
      inhibitory effect of modified protein was observed in cultures of human embryonic
      kidney cells (HEK293) and in rapidly proliferating mouse macrophage cell line ANA
      1. The only exclusion was human myeloid cell line U937: neither native nor
      modified apoA-I affected DNA synthesis in these cells. Thus, the regulatory
      effects of apoA-I are tissue-specific; this protein can produce either
      stimulatory or inhibitory effect on DNA biosynthesis in cells depending on its
      conformation.

PMID- 29177903
TI  - Comparison of Different Methods of Purification and Concentration in Production
      of Influenza Vaccine.
AB  - The overwhelming majority of influenza vaccines are prepared with the use of
      chicken embryo allantoic fluid. The presence of ovalbumin (this protein
      constitutes >60% total protein in the allantoic fluid) in the vaccine can lead to
      severe allergy. Hence, effective reduction of ovalbumin content is of crucial
      importance for vaccine production. We compared two methods of purification and
      concentration of influenza virus: zonal gradient ultracentrifugation and combined
      ultrafiltration/diafiltration and exclusion chromatography protocol, used for
      fabrication of seasonal vaccines. Combined chromatography is comparable with
      zonal centrifugation protocol by the results of ovalbumin removal (to meet
      standard requirements).

PMID- 29177904
TI  - Characteristics of Trophoblasts in Long-Term Culture.
AB  - We analyzed more than 40 cytotrophoblast cultures derived from cell islets that
      grew from trypsinized tissue fragments of placental microvilli. Phenotypic
      variability of trophoblasts was demonstrated. Changes in trophoblast morphology
      from epithelium-like or oval cells to bipolar and spindle-shaped or twisted and
      then to mesenchymal-like cells as well as intensive expression of cytokeratin-7
      and vimentin attested to epithelial-mesenchymal transition of trophoblasts during
      in vitro culturing. Analysis of the expression of specific markers in long-term
      trophoblast culture (>=7 passages) revealed the possibility of culture
      contamination with other non-trophoblast cells including fibroblasts. High risk
      of trophoblast culture contamination with rapidly growing cells necessitates
      regular control of the cultures used in fundamental studies. Our experiments
      confirmed the possibility of long-term culturing of cells maintaining trophoblast
      properties. The identity and purity of 4 trophoblast cultures free from
      contamination and retaining the properties of pure culture during long-term (>10
      passages) culturing in vitro were confirmed.

PMID- 29177905
TI  - Complex Analysis of Diffusion Transport and Microstructure of an Intervertebral
      Disk.
AB  - We studied the relationship between diffusion transport and morphological and
      microstructural organization of extracellular matrix of human intervertebral
      disk. Specimens of the lumbar intervertebral disks without abnormalities were
      studied ex vivo by diffusion-weighed magnetic resonance imaging, histological and
      immunohistochemical methods, and electron microscopy. Distribution of the
      diffusion coefficient in various compartments of the intervertebral disk was
      studied. Significant correlations between diffusion coefficient and cell density
      in the nucleus pulposus, posterior aspects of annulus fibrosus, and endplate at
      the level of the posterior annulus fibrosus were detected for each disk. In disks
      with nucleus pulposus diffusion coefficient below 15*10-4 mm2/sec, collagens X
      and XI were detected apart from aggrecan and collagens I and II. The results
      supplement the concept on the relationship between the microstructure and cell
      composition of various compartments of the intervertebral disk and parameters of
      nutrient transport.

PMID- 29177906
TI  - Experimental Study of Statistical Stability of Cardiointerval Samples.
AB  - In 1947 M. A. Bernstein proposed a hypothesis about "repetition without
      repetition" in biomechanics that was confirmed in psychophysiology by the Eskov
      Zinchenko effect. This effect can be applied to all parameters (except the
      parameters of the neuromuscular system) of human body homeostasis. For instance,
      this instability can be demonstrated for repeated samples of cardiointerval
      parameters (and other homeostasis parameters) of the human cardiorespiratory
      system. Within the framework of the new theory of chaos and self-organization, a
      method is proposed for calculation of matrices of paired comparisons of
      cardiointerval samples for assessing the physiological status of the human body
      and changes in homeostasis. Statistical instability of cardiointerval samples and
      their statistical distribution functions f(x) for successive cardiointerval
      samples in one subject is proven.

PMID- 29177907
TI  - Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) with Additional Protein
      Domain Synthesized in E. coli: In Vivo Osteoinductivity in Experimental Models on
      Small and Large Laboratory Animals.
AB  - Recombinant human bone morphogenetic protein-2 with an additional s-tag domain (s
      tag-BMP-2) synthesized in E. coli is characterized by higher solubility and
      activity than the protein without additional s-tag domain, which increases the
      yield during purification and simplifies protein introduction into the
      osteoplastic materials. The high osteoinductivity of the demineralized bone
      matrix with s-tag-BMP-2 was shown on the model of regeneration of cranial defects
      of a critical size in mice and on the model of implantation of porous titanium
      matrix into defects of femoral and tibial bones in rabbits.

PMID- 29177908
TI  - Formation of Tissue-Engineered Construct of Human Cartilage Tissue in a Flow
      Through Bioreactor.
AB  - We performed culturing of a cell-engineered construct of human cartilage tissue
      consisting of biopolymer microstructured collagen-containing hydrogel, human
      adipose tissue mesenchymal stromal cells, and induction chondrogenic culture
      medium in a specially designed flow-through bioreactor. On day 16 of the
      experiment, human adipose tissue mesenchymal stromal cells acquired flattened
      shape typical for chondroblasts, demonstrated high proliferative activity, and
      formed extracellular matrix. The observed histological changes in the cultured
      system attested to the beginning of the formation of a tissue-engineered
      construct of human cartilage tissue.

PMID- 29177909
TI  - Stem Cells and Progenitors in Human Peripheral Blood Get Activated by Extremely
      Active Resveratrol (XARTM).
AB  - Resveratrol generated enormous interest as it improved functions of multiple
      organs and could delay aging in animal models. However, basic mechanism of action
      was not understood and due to poor bioavailability, it has failed to enter the
      market. A highly active nano-formulation of resveratrol (XARTM) with enhanced
      bioavailability is now available. Present study was undertaken to evaluate its
      effects on stem cells biology in the human peripheral blood. Twelve healthy
      participants were enrolled of which five received XARTM, five were age-matched
      placebo controls and two were 76 and 85 years old. Peripheral blood was processed
      to study serum profile to monitor cardiac and pancreatic functions and subjected
      to density gradient centrifugation to enrich pluripotent (VSELs) and adult stem
      cells that get enriched along with red blood cells and in the Buffy coat
      respectively on Day 2 and Day 15 after XARTM treatment. The XARTM treatment
      resulted in an increased expression of pluripotency transcripts specific for
      VSELs (Oct-4A, Nanog and Sox2) on D2; specific transcripts for differentiation in
      the progenitors including Oct-4, Ikaros, CD14, CD90 on D15, and anti-ageing and
      tumor suppressor transcripts NAD, SIRT1, SIRT6 and p53 in both stem cells and
      progenitors. An improvement of cardiac and pancreatic markers in serum profile
      was also observed on D15. The decline in VSELs numbers with age and beneficial
      effects of the XARTM treatment were evident by up-regulation of specific
      transcripts and on serum profile. XARTM is a promising molecule that has the
      potential to activate pluripotent VSELs and tissue committed adult stem cells
      'progenitors' resulting in the rejuvenation of various body tissues and for
      improved, cancer-free health with advanced age.

PMID- 29177910
TI  - Characteristic and Source of Atmospheric PM10- and PM2.5-bound PAHs in a Typical
      Metallurgic City Near Yangtze River in China.
AB  - The characteristics of atmospheric PM10- and PM2.5-bound polycyclic aromatic
      hydrocarbons (PAHs) were investigated in Tongling city, China. Results showed
      that the total concentrations of PM10- and PM2.5-bound PAHs exhibited distinct
      seasonal and spatial variability. The metallurgic sites showed the highest PAH
      concentrations, which is mainly attributed to the metallurgic activities (mainly
      copper ore smelting) and coal combustion as the smelting fuel. The rural area
      showed the lowest concentrations, but exhibited significant increase from summer
      to autumn. This seasonal fluctuation is mainly caused by the biomass burning at
      the sites in the harvest season. The diagnostic ratio indicated that the main
      PAHs sources were vehicle exhausts, coal combustion and biomass burning. The
      total BaP equivalent concentration (BAP-TEQ) was found to be maximum at DGS site
      in winter, whereas it was minimum at BGC site in summer. Risk assessment
      indicates that residential exposure to PAHs in the industrial area, especially in
      the winter season, may pose a greater inhalation cancer risk than people living
      in living area and rural area.

PMID- 29177911
TI  - Mechanisms of Sustained Neutrophilia in Patient WHIM-09, Cured of WHIM Syndrome
      by Chromothripsis.
AB  - WHIM-09 is the first patient described with WHIM syndrome, an autosomal dominant
      form of neutropenia related to bone marrow retention of neutrophils. Originally
      diagnosed incorrectly with autoimmune neutropenia, the patient underwent
      splenectomy at age 9, but the absolute neutrophil count (ANC) did not rise.
      Subsequently, she was spontaneously cured by chromothripsis (chromosome
      shattering), which deleted the disease allele CXCR4 R334X , and 163 other genes,
      on chromosome 2 in a single hematopoietic stem cell (HSC). Chromothriptic CXCR4
      +/o HSCs replaced CXCR4 +/R334X WHIM HSCs, and the ANC rose to a new sustained
      and benign baseline ~ 2-3-fold above normal that had remained unexplained. Here,
      we show that splenectomized Cxcr4 +/o mice had sustained and benign neutrophilia,
      phenocopying neutrophilia in WHIM-09. In addition, WHIM-09's granulocyte
      macrophage precursor cells possessed increased granulocyte colony-forming
      activity ex vivo. Thus, WHIM-09's neutrophilia may be multifactorial, involving
      neutrophil-extrinsic factors (splenectomy), as well as CXCR4 haploinsufficiency
      dependent neutrophil-intrinsic factors (increased myeloid precursor cell
      differentiation). The strong bone marrow retention signal for neutrophils
      conferred by the WHIM mutation may have prevented neutrophilia after splenectomy
      until the mutation was deleted by chromothripsis.

PMID- 29177912
TI  - Are Hypomanic/Manic Episodes "Induced by" or "Associated with" Quetiapine
      Initiation?

PMID- 29177914
TI  - [Oncological surgery of the stomach and esophagus].

PMID- 29177913
TI  - Evaluation of the novel TSPO radiotracer [18F] VUIIS1008 in a preclinical model
      of cerebral ischemia in rats.
AB  - BACKGROUND: In vivo positron-emission tomography (PET) imaging of transporter
      protein (TSPO) expression is an attractive and indispensable tool for the
      diagnosis and therapy evaluation of neuroinflammation after cerebral ischemia.
      Despite several radiotracers have shown an excellent capacity to image
      neuroinflammation, novel radiotracers such as [18F] VUIIS1008 have shown
      promising properties to visualize and quantify the in vivo expression of TSPO.
      METHODS: Longitudinal in vivo magnetic resonance (MRI) and PET imaging studies
      with the novel TSPO radiotracer 2-(5,7-diethyl-2-(4-(2-[18F] fluoroethoxy)
      phenyl) pyrazolo [1,5-a] pyrimidin-3-yl)-N, N-diethylacetamide ([18F] VUIIS1008),
      and (N, N-diethyl-2-(2-[4-(2-fluoroethoxy)-phenyl]-5,7-dimethyl-pyrazolo [1,5-a]
      yrimidin-3-yl)-acetamide ([18F] DPA-714) were carried out before and at days 1,
      3, 7, 14, 21, and 28 following the transient middle cerebral artery occlusion
      (MCAO) in rats. RESULTS: MRI images showed the extension and evolution of the
      brain infarction after ischemic stroke in rats. PET imaging with [18F] VUIIS1008
      and [18F] DPA714 showed a progressive increase in the ischemic brain hemisphere
      during the first week, peaking at day 7 and followed by a decline from days 14 to
      28 after cerebral ischemia. [18F] DPA714 uptake showed a mild uptake increase
      compared to [18F] VUIIS1008 in TSPO-rich ischemic brain regions. In vivo [18F]
      VUIIS1008 binding displacement with VUIIS1008 was more efficient than DPA714.
      Finally, immunohistochemistry confirmed a high expression of TSPO in microglial
      cells at day 7 after the MCAO in rats. CONCLUSIONS: Altogether, these results
      suggest that [18F] VUIIS1008 could become a valuable tool for the diagnosis and
      treatment evaluation of neuroinflammation following ischemic stroke.

PMID- 29177915
TI  - [Precancerous and early stage cancer of the bile duct system].
AB  - Early stage cancer of the bile duct system is still difficult to diagnose. In
      cases of suspect lesions a stepwise diagnostic procedure consisting of computed
      tomography (CT), magnetic resonance imaging (MRI) with MR cholangiography (MRC)
      and possibly endoscopic retrograde cholangiopancreatography (ERCP) with brush
      cytology should immediately be carried out. If there is a sufficient suspicion
      for premalignancy or early stage cancer the indications for surgical intervention
      should clearly be defined. Only resection can lead to a decrease in the
      recurrence rate and a better long-term outcome. If the patient is in a
      functionally nonresectable condition the possibility of liver transplantation
      should be considered.

PMID- 29177916
TI  - Direct to consumer genetic testing-law and policy concerns in Ireland.
AB  - BACKGROUND: With rapid scientific and technological advances, the past few years
      has witnessed the emergence of a new genetic era and a growing understanding of
      the genetic make-up of human beings. These advances have propelled the
      introduction of companies offering direct to consumer (DTC) genetic testing,
      which facilitates the direct provision of such tests to consumers, (for example,
      via the internet). Although DTC genetic testing offers benefits by enhancing
      consumer accessibility to such technology, promoting proactive healthcare and
      increasing genetic awareness, it presents a myriad of challenges, from an
      ethical, legal and regulatory perspective. As DTC genetic testing usually
      eliminates the need for a medical professional in accessing genetic tests, this
      lack of professional guidance and counselling may result in misinterpretation and
      confusion regarding results. In addition, an evident concern relates to the
      scientific validity and quality of these tests. A further problem arising is the
      lack or inadequacy of regulation in this field. Despite the increasing
      accessibility of DTC genetic testing, this legislative vacuum is apparent in
      Ireland, where there is no concrete legislation. AIMS AND OBJECTIVES: This
      article explores the main ethical, legal and regulatory issues arising with the
      advent of rapid advances in DTC genetic testing in Ireland. Further, with
      inevitable future advances in genetic science, as well as increasing internet
      accessibility, the challenges presented are likely to become more amplified.
      CONCLUSIONS: In consideration of the ethical and legal challenges, this paper
      highlights the regulation of DTC genetic testing as a growing concern in Ireland,
      recognising its importance to both the scientific community as well as in respect
      of enhancing consumer confidence in such technologies.

PMID- 29177918
TI  - Disruptive Behavior Treatment Progress as a Function of Therapy Focus and Youth
      Diagnosis in a Community Mental Health Setting.
AB  - Monthly disruptive behavior treatment progress for 613 youth ages 7-18 receiving
      intensive in-home services was examined. Multilevel modeling indicated carrying a
      depressive mood diagnosis predicted less disruptive behavior progress compared to
      youth with only externalizing diagnoses. Paradoxically, more monthly focus on
      disruptive behavior treatment targets predicted lower concurrent progress
      ratings, while greater focus on depressive mood targets predicted greater
      disruptive behavior progress for youth with a depressive mood diagnosis. Findings
      held when other predictors of disruptive behavior progress were included as
      covariates, including episode length, youth age, and functional impairment.
      Treatment and research implications are discussed.

PMID- 29177917
TI  - MRI and multiple sclerosis--the evolving role of MRI in the diagnosis and
      management of MS: the radiologist's perspective.
AB  - Magnetic resonance imaging (MRI) plays an integral role in the management of
      multiple sclerosis (MS), from both diagnostic and therapeutic perspectives. This
      2-part review aims to detail the evolving and expanding role of MRI for both
      radiologists and neurologists. In this article, we discuss the diagnostic
      criteria for MS relevant to radiologists, as well as its varying imaging
      manifestations. The role of MRI in therapeutic modification and complications are
      discussed.

PMID- 29177919
TI  - Entropy production in a fluid-solid system far from thermodynamic equilibrium.
AB  - The terminal orientation of a rigid body in a moving fluid is an example of a
      dissipative system, out of thermodynamic equilibrium and therefore a perfect
      testing ground for the validity of the maximum entropy production principle
      (MaxEP). Thus far, dynamical equations alone have been employed in studying the
      equilibrium states in fluid-solid interactions, but these are far too complex and
      become analytically intractable when inertial effects come into play. At that
      stage, our only recourse is to rely on numerical techniques which can be
      computationally expensive. In our past work, we have shown that the MaxEP is a
      reliable tool to help predict orientational equilibrium states of highly
      symmetric bodies such as cylinders, spheroids and toroidal bodies. The MaxEP
      correctly helps choose the stable equilibrium in these cases when the system is
      slightly out of thermodynamic equilibrium. In the current paper, we expand our
      analysis to examine i) bodies with fewer symmetries than previously reported, for
      instance, a half-ellipse and ii) when the system is far from thermodynamic
      equilibrium. Using two-dimensional numerical studies at Reynolds numbers ranging
      between 0 and 14, we examine the validity of the MaxEP. Our analysis of flow past
      a half-ellipse shows that overall the MaxEP is a good predictor of the
      equilibrium states but, in the special case of the half-ellipse with aspect ratio
      much greater than unity, the MaxEP is replaced by the Min-MaxEP, at higher
      Reynolds numbers when inertial effects come into play. Experiments in
      sedimentation tanks and with hinged bodies in a flow tank confirm these
      calculations.

PMID- 29177920
TI  - Examining the Durability of Colorectal Cancer Screening Awareness and Health
      Beliefs Among Medically Underserved Patients: Baseline to 12 months Post
      Intervention.
AB  - The current study examines changes in awareness and health beliefs from baseline
      to 12 months post-intervention following receipt of one of two colorectal cancer
      (CRC) educational interventions that aimed to promote CRC screening among a
      racially and ethnically diverse and medically underserved population.
      Participants (N = 270) were enrolled in a randomized controlled trial to increase
      CRC screening and completed both baseline and 12-month follow-up assessments.
      Participants were aged 50-75, at average CRC risk, not up-to-date with CRC
      screening guidelines, and receiving care at one of three community-based clinics.
      Participants were randomized to receive either a targeted, low-literacy
      intervention informed by the Preventive Health Model [PHM] (photonovella and DVD
      plus fecal immunochemical test [FIT]) or a non-targeted intervention (standard
      educational brochure plus FIT). Changes in CRC awareness and health beliefs from
      baseline to 12 months were examined both within and between intervention groups
      using Student's t tests. Participants in both intervention conditions
      demonstrated an increase in CRC awareness, PHM social influence, and trust in the
      healthcare system (all p's < .0001), with no significant between-group
      differences. Among those receiving the targeted intervention, there also was an
      increase in PHM salience (p < .05). Among individuals receiving the non-targeted
      intervention, there was an increase in PHM response efficacy (p < .01) and PHM
      self-efficacy (p < .0001). Both CRC screening interventions promoted positive
      changes in awareness and several health beliefs from baseline to 12 months,
      suggesting important benefits of CRC education. Regardless of whether education
      was targeted or non-targeted, providing CRC screening education successfully
      promoted durable changes in awareness and health beliefs.

PMID- 29177921
TI  - Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla
      chinensis Maxim against H1N1 influenza virus.
AB  - OBJECTIVE: The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly
      contain luteolin and apigenin. The study aims to examine the inhibitory effects
      of STF on anti-H1N1 influenza virus and its related molecular mechanisms in
      pneumonia mice. METHODS: The viral pneumonia mice were treated with Ribavirin or
      various doses of STF. We observed histological changes of lung by
      immunohistochemistry and measured lung index to value anti-influenza virus
      effects of STF. The concentrations of inflammatory cytokines and anti-oxidant
      factors were detected by ELISA. RT-PCR and western blot assays were used to
      determine the expression level of TLR pathway's key genes and proteins in lung
      tissues. RESULTS: We found that the pathological changes of lung in the viral
      pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576
      mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL
      6, TNF-alpha, IFN-gamma, and NO) and down-regulation (IL-2, SOD and GSH) of
      inflammatory cytokines and anti-oxidant factors were associated with higher
      clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile,
      the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-kappaB p65 of the TLR
      pathway were reduced by STF treatment. CONCLUSIONS: This study suggested that STF
      may be a promising candidate for treating H1N1 influenza and subsequent viral
      pneumonia.

PMID- 29177922
TI  - SGLT1 and SGLT1 Inhibitors: A Role to Be Assessed in the Current Clinical
      Practice.
AB  - Diabetes is a complex disease of increasingly common occurrence worldwide.
      Attaining optimal glycemic control is the main challenge to prevent the
      development of diabetes-related complications and/or to stop their progression.
      In recent years, the pharmacologic toolkit for the treatment of diabetes has
      considerably expanded, thus paving the way to more pathophysiology-oriented
      therapies. For instance, the sodium-glucose cotransporters SGLT2 and SGLT1 have
      been in the spotlight because of better knowledge of their physiology and
      therapeutic potential. At present, whereas the SGLT2 inhibitors are widely
      applied in current clinical practice as an effective and well-tolerated treatment
      that increases the urinary excretion of glucose, less is known about the use of
      SGLT1 inhibitors. SGLT1s are of primary importance in the small intestine, an
      organ that does not express SGLT2, while in the kidney they are expressed in the
      late renal proximal tubules, where it reabsorbs the glucose escaped from the
      upstream SGLT2. Hence, SGLT1-mediated glucose reabsorption in the kidney is
      increased when the tubular glucose load overwhelms the capacity of SGLT2 or when
      the latter is inhibited. The role of SGLT1 in intestinal and renal glucose
      transport makes the transporter a potential target for antidiabetic therapy.
      Here, we briefly report the evidence on LX2761, a new inhibitor against SGLT1 and
      SGLT2 in vitro, which acts in vivo as a selective inhibitor of SGLT1 in the
      gastrointestinal tract. LX2761 improves glycemic control without the glycosuria
      related side effects of SGLT2 inhibitors, particularly genitourinary tract
      infections. However, whether it represents a valid therapeutic option for all
      patients with diabetes or is more appropriate for specific phenotypes, e.g.,
      patients with concomitant diabetes and chronic kidney disease, who may benefit
      less from the renal mechanism of selective SGLT2 inhibitors, remains to be tested
      in large randomized controlled trials.

PMID- 29177923
TI  - Skin Autofluorescence is a Noninvasive Surrogate Marker for Diabetic
      Microvascular Complications and Carotid Intima-Media Thickness in Japanese
      Patients with Type 2 Diabetes: A Cross-sectional Study.
AB  - INTRODUCTION: Advanced glycation end-products (AGEs) are known to play an
      important role in the pathogenesis of diabetic complications. Skin
      autofluorescence (AF), a marker of AGE accumulation in tissue, can be measured
      noninvasively using a skin AF reader. The present study aimed to evaluate the
      relationships of skin AF with diabetic microvascular complications and carotid
      intima-media thickness (IMT), a surrogate marker for atherosclerosis, in Japanese
      subjects with type 2 diabetes (T2D). METHODS: One hundred sixty-two subjects with
      T2D and 42 nondiabetic control subjects attending the outpatient clinic were
      examined. Skin AF and carotid max-IMT were measured using an AGE ReaderTM and
      ultrasonography, respectively. Nephropathy was classified into five stages based
      on the urinary albumin-to-creatinine ratio (UACR) as follows: (1) pre-nephropathy
      (stage 1) (UACR < 30 mg/g Cr); (2) incipient nephropathy (stage 2) (30 <= UACR <
      300 mg/g Cr); (3) overt nephropathy (stage 3) (UACR >= 300 mg/g Cr); (4) kidney
      failure (stage 4) (estimated glomerular filtration rate (eGFR) < 30
      ml/min/1.732); and (5) dialysis therapy (stage 5). Patients with kidney failure
      and those receiving dialysis therapy were excluded because the sample size was
      too small. Retinopathy was diagnosed as nondiabetic retinopathy (NDR),
      nonproliferative retinopathy (NPDR), or proliferative retinopathy (PDR). Diabetic
      peripheral neuropathy (DPN) was diagnosed if two or more of the following were
      present: neuropathic symptoms (decreased sensation, positive neuropathic sensory
      symptoms), symmetric decreased distal sensation, and unequivocally decreased or
      absent ankle reflexes. RESULTS: Skin AF values were significantly higher in
      subjects with T2D (2.53 +/- 0.45 AU) than in nondiabetic subjects (2.19 +/- 0.34
      AU, p < 0.001). Skin AF significantly increased with the severity of DPN (2.39 +/
      0.37 with DPN vs 2.80 +/- 0.48 without DPN, p < 0.001), retinopathy (NDR 2.42 +/
      0.45, mild and moderate NPDR 2.64 +/- 0.42, p = 0.042, severe NPDR and PDR 2.85
      +/- 0.35, p < 0.001), and nephropathy (pre-nephropathy 2.42 +/- 0.44, incipient
      nephropathy 2.62 +/- 0.45, p = 0.049, overt nephropathy 2.59 +/- 0.46, p = 0.80).
      Skin AF was an independent determinant of the presence of DPN (OR 8.49, 95% CI
      2.04-44.32, p = 0.006) and retinopathy (OR 3.73, 95% CI 1.20-12.90, p = 0.028)
      but not of diabetic nephropathy after correcting for confounding factors. In
      addition, skin AF (beta = 0.170, p = 0.029) was an independent determinant of max
      IMT, as was age (beta = 0.436, p < 0.0001), after adjusting for other risk
      factors. CONCLUSION: Skin AF as measured using an AGE Reader is a noninvasive
      surrogate marker for diabetic microvascular complications and early-stage
      atherosclerosis.

PMID- 29177924
TI  - The diagnostic accuracy of high b-value diffusion- and T2-weighted imaging for
      the detection of prostate cancer: a meta-analysis.
AB  - PURPOSE: This study aims to investigate the role of diffusion-weighted imaging
      (DWI) and T2-weighted imaging (T2WI) in combination for the detection of prostate
      cancer, specifically assessing the role of high b-values (> 1000 s/mm2), with a
      systematic review and meta-analysis of the existing published data. METHODS: The
      electronic databases MEDLINE, EMBASE, and OpenSIGLE were searched between
      inception and September 1, 2017. Eligible studies were those that reported the
      sensitivity and specificity of DWI and T2WI for the diagnosis of prostate cancer
      by visual assessment using a histopathologic reference standard. The QUADAS-2
      critical appraisal tool was used to assess the quality of included studies. A
      meta-analysis with pooling of sensitivity, specificity, likelihood, and
      diagnostic odds ratios was undertaken, and a summary receiver-operating
      characteristics (sROC) curve was constructed. Predetermined subgroup analysis was
      also performed. RESULTS: Thirty-three studies were included in the final
      analysis, evaluating 2949 patients. The pooled sensitivity and specificity were
      0.69 (95% CI 0.68-0.69) and 0.84 (95% CI 0.83-0.85), respectively, and the sROC
      AUC was 0.84 (95% CI 0.81-0.87). Subgroup analysis showed significantly better
      sensitivity with high b-values (> 1000 s/mm2). There was high statistical
      heterogeneity between studies. CONCLUSION: The diagnostic accuracy of combined
      DWI and T2WI is good with high b-values (> 1000 s/mm2) seeming to improve overall
      sensitivity while maintaining specificity. However, further large-scale studies
      specifically looking at b-value choice are required before a categorical
      recommendation can be made.

PMID- 29177925
TI  - Genetics of pancreatic cancer and implications for therapy.
AB  - Pancreatic cancer is a highly lethal disease with a dismal 5-year prognosis.
      Knowledge of its genetics may help in identifying new methods for patient
      screening, and cancer treatment. In this review, we will describe the most common
      mutations responsible for the genesis of pancreatic cancer and their impact on
      screening, patterns of disease progression, and therapy.

PMID- 29177927
TI  - The double channel pylorus.

PMID- 29177926
TI  - Can physician gestalt predict survival in patients with resectable pancreatic
      adenocarcinoma?
AB  - PURPOSE: Clinician gestalt may hold unexplored information that can be
      capitalized upon to improve existing nomograms. The study objective was to
      evaluate physician ability to predict 2-year overall survival (OS) in resected
      pancreatic ductal adenocarcinoma (PDAC) patients based on pre-operative clinical
      characteristics and routine CT imaging. METHODS: Ten surgeons and two
      radiologists were provided with a clinical vignette (including age, gender,
      presenting symptoms, and pre-operative CA19-9 when available) and pre-operative
      CT scan for 20 resected PDAC patients and asked to predict the probability of
      each patient reaching 2-year OS. Receiver operating characteristic curves were
      used to assess agreement and to compare performance with an established
      institutional nomogram. RESULTS: Ten surgeons and 2 radiologists participated in
      this study. The area under the curve (AUC) for all physicians was 0.707 (95% CI
      0.642-0.772). Attending physicians with > 5 years experience performed better
      than physicians with < 5 years of clinical experience since completion of post
      graduate training (AUC = 0.710, 95% CI [0.536-0.884] compared to AUC = 0.662, 95%
      CI [0.398-0.927]). Radiologists performed better than surgeons (AUC = 0.875, 95%
      CI [0.765-0.985] compared to AUC = 0.656, 95% CI [0.580-0.732]). All but one
      physician outperformed the clinical nomogram (AUC = 0.604). CONCLUSIONS: This
      pilot study demonstrated significant promise in the quantification of physician
      gestalt. While PDAC remains a difficult disease to prognosticate, physicians,
      particularly those with more clinical experience and radiologic expertise, are
      able to perform with higher accuracy than existing nomograms in predicting 2-year
      survival.

PMID- 29177928
TI  - The bottom line: MRI and CT findings of unusual rectal and perirectal pathology.
AB  - Although common nonspecific symptoms (i.e., rectal bleeding, pelvic pressure, and
      change in bowel habits) are associated with rectal cancer, occasionally these are
      related to a different underlying disease. Over the past few years, considerable
      progress has been made in imaging of the rectum. Specifically, new magnetic
      resonance techniques and capabilities provide impressive high-resolution
      assessment of the rectal wall and enable evaluation and characterization of the
      perirectal tissues. This paper reviews imaging findings of uncommon causes of
      rectal and perirectal pathology that may be clinically confounded with rectal
      cancer. Radiologists need to be aware of uncommon pathologies in this region in
      order to facilitate optimal management decisions.

PMID- 29177929
TI  - Structure and dynamics of mesophilic variants from the homing endonuclease I
      DmoI.
AB  - I-DmoI, from the hyperthermophilic archaeon Desulfurococcus mobilis, belongs to
      the LAGLIDADG homing endonuclease protein family. Its members are highly specific
      enzymes capable of recognizing long DNA target sequences, thus providing
      potential tools for genome manipulation. Working towards this particular
      application, many efforts have been made to generate mesophilic variants of I
      DmoI that function at lower temperatures than the wild-type. Here, we report a
      structural and computational analysis of two I-DmoI mesophilic mutants. Despite
      very limited structural variations between the crystal structures of these
      variants and the wild-type, a different dynamical behaviour near the cleavage
      sites is observed. In particular, both the dynamics of the water molecules and
      the protein perturbation effect on the cleavage site correlate well with the
      changes observed in the experimental enzymatic activity.

PMID- 29177930
TI  - Value of in vitro acoustic radiation force impulse application on uterine
      adenomyosis.
AB  - PURPOSE: Adenomyosis is the presence of endometrial glandular and stromal tissue
      in the myometrium. This phenomenon can be the cause of excessive bleeding and
      menstrual pain in premenopausal women. Diagnosis of adenomyosis may present
      difficulty with conventional methods such as ultrasound and magnetic resonance
      imaging. Frequently, diagnosis is accomplished retrospectively based on the
      hysterectomy specimen. MATERIALS AND METHODS: This is a prospective case control
      study done in vitro on 90 patients' hysterectomy specimens. Acoustic radiation
      force impulse (ARFI) and color elastography were used to determine the elasticity
      of hysterectomy specimens of patients undergoing indicated surgeries. Based on
      histopathological examinations, two groups were formed: a study group (n = 28
      with adenomyosis) and a control group (n = 62-without adenomyosis). RESULTS:
      Elasticity measurements of tissue with adenomyosis were observed to be
      significantly higher than measurements of normal myometrial tissue (p < 0.01).
      Uterine fibroids were found to have higher values on ARFI study compared to
      normal myometrial tissues (p < 0.01). CONCLUSION: The findings lead to the
      conclusion that adenomyosis tissue is significantly softer than the normal
      myometrium. ARFI was found to be beneficial in differentiating myometrial tissue
      with adenomyosis from normal myometrial tissue. It was found to be feasible and
      beneficial to implement ARFI in daily gynecology practice for diagnosis of
      adenomyosis.

PMID- 29177931
TI  - Evaluating the interaction of a tracheobronchial stent in an ovine in-vivo model.
AB  - Tracheobronchial stents are used to restore patency to stenosed airways. However,
      these devices are associated with many complications such as stent migration,
      granulation tissue formation, mucous plugging and stent strut fracture. Of these,
      granulation tissue formation is the complication that most frequently requires
      costly secondary interventions. In this study a biomechanical lung modelling
      framework recently developed by the authors to capture the lung in-vivo stress
      state under physiological loading is employed in conjunction with ovine pre
      clinical stenting results and device experimental data to evaluate the effect of
      stent interaction on granulation tissue formation. Stenting is simulated using a
      validated model of a prototype covered laser-cut tracheobronchial stent in a semi
      specific biomechanical lung model, and physiological loading is performed. Two
      computational methods are then used to predict possible granulation tissue
      formation: the standard method which utilises the increase in maximum principal
      stress change, and a newly proposed method which compares the change in contact
      pressure over a respiratory cycle. These computational predictions of granulation
      tissue formation are then compared to pre-clinical stenting observations after a
      6-week implantation period. Experimental results of the pre-clinical stent
      implantation showed signs of granulation tissue formation both proximally and
      distally, with a greater proximal reaction. The standard method failed to show a
      correlation with the experimental results. However, the contact change method
      showed an apparent correlation with granulation tissue formation. These results
      suggest that this new method could be used as a tool to improve future device
      designs.

PMID- 29177932
TI  - A computational algorithm to simulate disorganization of collagen network in
      injured articular cartilage.
AB  - Cartilage defects are a known risk factor for osteoarthritis. Estimation of
      structural changes in these defects could help us to identify high risk defects
      and thus to identify patients that are susceptible for the onset and progression
      of osteoarthritis. Here, we present an algorithm combined with computational
      modeling to simulate the disorganization of collagen fibril network in injured
      cartilage. Several potential triggers for collagen disorganization were tested in
      the algorithm following the assumption that disorganization is dependent on the
      mechanical stimulus of the tissue. We found that tensile tissue stimulus alone
      was unable to preserve collagen architecture in intact cartilage as collagen
      network reoriented throughout the cartilage thickness. However, when collagen
      reorientation was based on both tensile tissue stimulus and tensile collagen
      fibril strains or stresses, the collagen network architecture was preserved in
      intact cartilage. Using the same approach, substantial collagen reorientation was
      predicted locally near the cartilage defect and particularly at the cartilage
      bone interface. The developed algorithm was able to predict similar structural
      findings reported in the literature that are associated with experimentally
      observed remodeling in articular cartilage. The proposed algorithm, if further
      validated, could help to predict structural changes in articular cartilage
      following post-traumatic injury potentially advancing to impaired cartilage
      function.

PMID- 29177933
TI  - Modeling the effect of collagen fibril alignment on ligament mechanical behavior.
AB  - Ligament mechanical behavior is primarily regulated by fibrous networks of type I
      collagen. Although these fibrous networks are typically highly aligned, healthy
      and injured ligament can also exhibit disorganized collagen architecture. The
      objective of this study was to determine whether variations in the collagen
      fibril network between neighboring ligaments can predict observed differences in
      mechanical behavior. Ligament specimens from two regions of bovine fetlock
      joints, which either exhibited highly aligned or disorganized collagen fibril
      networks, were mechanically tested in uniaxial tension. Confocal microscopy and
      FiberFit software were used to quantify the collagen fibril dispersion and mean
      fibril orientation in the mechanically tested specimens. These two structural
      parameters served as inputs into an established hyperelastic constitutive model
      that accounts for a continuous distribution of planar fibril orientations. The
      ability of the model to predict differences in the mechanical behavior between
      neighboring ligaments was tested by (1) curve fitting the model parameters to the
      stress response of the ligament with highly aligned fibrils and then (2) using
      this model to predict the stress response of the ligament with disorganized
      fibrils by only changing the parameter values for fibril dispersion and mean
      fibril orientation. This study found that when using parameter values for fibril
      dispersion and mean fibril orientation based on confocal imaging data, the model
      strongly predicted the average stress response of ligaments with disorganized
      fibrils ([Formula: see text]); however, the model only successfully predicted the
      individual stress response of ligaments with disorganized fibrils in half the
      specimens tested. Model predictions became worse when parameters for fibril
      dispersion and mean fibril orientation were not based on confocal imaging data.
      These findings emphasize the importance of collagen fibril alignment in ligament
      mechanics and help advance a mechanistic understanding of fibrillar networks in
      healthy and injured ligament.

PMID- 29177934
TI  - Correction to: Industrial antifoam agents impair ethanol fermentation and induce
      stress responses in yeast cells.
AB  - The article "Industrial antifoam agents impair ethanol fermentation and induce
      stress responses in yeast cells" was originally published Online First without
      open access. After publication in volume 101, issue 22, page 8237-8248, the
      author decided to opt for Open Choice and to make the article an open access
      publication.

PMID- 29177935
TI  - Pool deconvolution approach for high-throughput gene mining from Bacillus
      thuringiensis.
AB  - Novel genes from Bacillus thuringiensis (Bt) are required for effective
      deployment in agriculture, human health, and forestry. In an improvement over
      conventional PCR-based screening, next generation sequencing (NGS) has been used
      for identification of new genes of potential interest from Bt strains, but cost
      becomes a constraint when several isolates are to be sequenced. We demonstrate
      the potential of a DNA pooling strategy known as pool deconvolution to identify
      commercially important toxin genes from 36 native Bt isolates. This strategy is
      divided into three steps: (a) DNA pooling, (b) short read sequence assembly
      followed by gene mining, and (c) host isolate identification. With this approach,
      we have identified insecticidal protein (ip) genes including nine three-domain
      (3D) cry genes, three cyt-type genes, three mtx genes (mosquitocidal toxin), and
      one bin and vip-type gene each. Three cry-type and three cyt-type genes were
      cloned, out of which, two cry-type genes, ip11 and ip13, were named as cry4Ca2
      and cry52Ca1, respectively by the Bacillus thuringiensis nomenclature committee (
      http://www.biols.susx.ac.uk/Home/Neil_Crickmore/BT/ ). Our results show that the
      pool deconvolution approach is well suited for high-throughput gene mining in
      bacteria.

PMID- 29177936
TI  - Is bacterial vaginosis a disease?
AB  - Bacterial vaginosis (BV) has been described as a disease, a disorder, a vaginal
      inflammation, an infection, a microbial dysbiosis, a condition, and in some
      women, a normal situation. In order to fit the definition of a disease, BV would
      have to be a disorder of function that produces specific signs or symptoms or
      affects the vagina in an aberrant way. Yet, there is little consistency in
      patients reporting signs and symptoms when BV is diagnosed, nor the appearance of
      aberrations to the vagina. If BV is not a disease, there are implications for its
      management and coverage of treatment costs, and for the conclusions drawn in a
      multitude of previous studies. It is time for BV to be redefined and for the
      various subsets to be given a separate terminology with specific methods of
      diagnosis and appropriate treatment and preventive strategies.

PMID- 29177937
TI  - Biosynthesis of 2-aminooctanoic acid and its use to terminally modify a
      lactoferricin B peptide derivative for improved antimicrobial activity.
AB  - Terminal modification of peptides is frequently used to improve their
      hydrophobicity. While N-terminal modification with fatty acids (lipidation) has
      been reported previously, C-terminal lipidation is limited as it requires the use
      of linkers. Here we report the use of a biocatalyst for the production of an
      unnatural fatty amino acid, (S)-2-aminooctanoic acid (2-AOA) with enantiomeric
      excess > 98% ee and the subsequent use of 2-AOA to modify and improve the
      activity of an antimicrobial peptide. A transaminase originating from
      Chromobacterium violaceum was employed with a conversion efficiency 52-80%
      depending on the ratio of amino group donor to acceptor. 2-AOA is a fatty acid
      with amino functionality, which allowed direct C- and N-terminal conjugation
      respectively to an antimicrobial peptide (AMP) derived from lactoferricin B. The
      antibacterial activity of the modified peptides was improved by up to 16-fold.
      Furthermore, minimal inhibitory concentrations (MIC) of C-terminally modified
      peptide were always lower than N-terminally conjugated peptides. The C-terminally
      modified peptide exhibited MIC values of 25 MUg/ml for Escherichia coli, 50
      MUg/ml for Bacillus subtilis, 100 MUg/ml for Salmonella typhimurium, 200 MUg/ml
      for Pseudomonas aeruginosa and 400 MUg/ml for Staphylococcus aureus. The C
      terminally modified peptide was the only peptide tested that showed complete
      inhibition of growth of S. aureus.

PMID- 29177938
TI  - Stabilization of multimeric sucrose synthase from Acidithiobacillus caldus via
      immobilization and post-immobilization techniques for synthesis of UDP-glucose.
AB  - Sucrose synthases (SuSys) have been attracting great interest in recent years in
      industrial biocatalysis. They can be used for the cost-effective production of
      uridine 5'-diphosphate glucose (UDP-glucose) or its in situ recycling if coupled
      to glycosyltransferases on the production of glycosides in the food,
      pharmaceutical, nutraceutical, and cosmetic industry. In this study, the
      homotetrameric SuSy from Acidithiobacillus caldus (SuSyAc) was immobilized
      stabilized on agarose beads activated with either (i) glyoxyl groups, (ii)
      cyanogen bromide groups, or (iii) heterogeneously activated with both glyoxyl and
      positively charged amino groups. The multipoint covalent immobilization of SuSyAc
      on glyoxyl agarose at pH 10.0 under optimized conditions provided a significant
      stabilization factor at reaction conditions (pH 5.0 and 45  degrees C). However,
      this strategy did not stabilize the enzyme quaternary structure. Thus, a post
      immobilization technique using functionalized polymers, such as polyethyleneimine
      (PEI) and dextran-aldehyde (dexCHO), was applied to cross-link all enzyme
      subunits. The coating of the optimal SuSyAc immobilized glyoxyl agarose with a
      bilayer of 25 kDa PEI and 25 kDa dexCHO completely stabilized the quaternary
      structure of the enzyme. Accordingly, the combination of immobilization and post
      immobilization techniques led to a biocatalyst 340-fold more stable than the non
      cross-linked biocatalyst, preserving 60% of its initial activity. This
      biocatalyst produced 256 mM of UDP-glucose in a single batch, accumulating 1 M
      after five reaction cycles. Therefore, this immobilized enzyme can be of great
      interest as a biocatalyst to synthesize UDP-glucose.

PMID- 29177939
TI  - Development of a high-copy-number plasmid via adaptive laboratory evolution of
      Corynebacterium glutamicum.
AB  - Beyond its traditional role as an L-amino acid producer, Corynebacterium
      glutamicum has recently received significant attention regarding its use in the
      production of various biochemicals and recombinant proteins. However, despite
      these attributes, limitations in genetic tools are still hampering the
      engineering of C. glutamicum for use in more potential hosts. Here, we engineered
      a C. glutamicum via adaptive laboratory evolution to enhance the production of
      recombinant proteins. During the continuous cultivation, C. glutamicum producing
      enhanced green fluorescent proteins was screened using high-speed flow cytometer,
      and in the end, we successfully isolated an evolved strain with a fluorescence
      intensity 4.5-fold higher than that of the original strain. Extensive analysis of
      the evolved strain confirmed that the plasmid prepared from the evolved strain
      contains the nonsense mutation in the parB locus, which mutation contributed to
      increasing the copy number of plasmid by approximately 10-fold compared to that
      of the wild type. To validate the usefulness of the high-copy-number plasmid, we
      examined the secretory production of endoxylanase and the bioconversion of xylose
      to xylonate using xylonate dehydrogenase. In the fed-batch cultivation, the use
      of the high-copy-number plasmid led to 1.4-fold increase in the production of
      endoxylanase (~ 1.54 g/L in culture medium) without cell growth retardation
      comparing cultivation with cells harboring original plasmid. The expression of
      xylonate dehydrogenase in the high-copy-number plasmid also improved the
      bioconversion into xylonic acid by approximately 1.5-fold compared to the
      original plasmid.

PMID- 29177940
TI  - Functional analysis of the dehydratase domains of a PUFA synthase from
      Thraustochytrium in Escherichia coli.
AB  - Thraustochytrium sp. 26185, a unicellular marine protist, synthesizes
      docosahexaenoic acid, an omega-3 very long chain polyunsaturated fatty acid (VLC
      PUFAs), by a polyunsaturated fatty acid (PUFA) synthase comprising three large
      subunits with multiple catalytic dehydratase (DH) domains critical for
      introducing double bonds at the specific position of fatty acids. To investigate
      functions of these DH domains, one DH domain from subunit-A and two DH domains
      from subunit-C of the PUFA synthase were dissected and expressed as stand-alone
      enzymes in Escherichia coli. The results showed that all these DH domains could
      complement the defective phenotype of a E. coli FabA temperature sensitive
      mutant, despite they have only modest sequence similarity with FabA, indicating
      they can function as 3-hydroxyacyl-ACP dehydratase for the biosynthesis of
      unsaturated fatty acids in E. coli. Site-directed mutagenesis analysis confirmed
      the authenticity of active site residues in these domains. In addition,
      overexpression of the three domains in a wild type E. coli strain resulted in the
      substantial alteration of fatty acid profiles including productions and ratio of
      unsaturated to saturated fatty acids. A combination of evidences from sequence
      comparison, functional expression, and mutagenesis analysis suggest that the DH
      domain from subunit-A is similar to DH domains from polyketide synthases, while
      the DH domains from subunit-C are more comparable to E. coli FabA in catalytic
      functions. Successful complementation and functional expression of the embedded
      DH domains from the PUFA synthase in E. coli is an important step towards for
      elucidating the molecular mechanism in the biosynthesis of VLC-PUFAs in
      Thraustochytrium.

PMID- 29177941
TI  - Investigation of Acute and Chronic Toxicity Trends of Pesticides Using High
      Throughput Bioluminescence Assay Based on the Test Organism Vibrio fischeri.
AB  - High-throughput acute and chronic toxicity tests using Vibrio fischeri were used
      to assess the toxicity of a variety of fungicides, herbicides, and
      neonicotinoids. The use of time points beyond the traditional 30 min of an acute
      test highlighted the sensitivity and applicability of the chronic toxicity test
      and indicated that for some compounds toxicity is underestimated using only the
      acute test. The comparison of EC50 values obtained from acute and chronic tests
      provided insight regarding the toxicity mode of action, either being direct or
      indirect. Using a structure-activity relationship approach similar to the one
      used in hazard assessments, the relationship between toxicity and key
      physicochemical properties of pesticides was investigated and trends were
      identified. This study not only provides new information regarding acute toxicity
      of some pesticides but also is one of the first studies to investigate the
      chronic toxicity of pesticides using the test organism V. fischeri. The findings
      demonstrated that the initial bioluminescence has a large effect on the
      calculated effective concentrations for target compounds in both acute and
      chronic tests, providing a way to improve and standardize the test protocol. In
      addition, the findings emphasize the need for additional investigation regarding
      the relationship between a toxicant's physicochemical properties and mode of
      action in nontarget organisms.

PMID- 29177942
TI  - The net effects of medical malpractice tort reform on health insurance losses:
      the Texas experience.
AB  - In this paper, we examine the influence of medical malpractice tort reform on the
      level of private health insurance company losses incurred. We employ a natural
      experiment framework centered on a series of tort reform measures enacted in
      Texas in 2003 that drastically altered the medical malpractice environment in the
      state. The results of a difference-in-differences analysis using a variety of
      comparison states, as well as a difference-in-difference-in-differences analysis,
      indicate that ameliorating medical malpractice risk has little effect on health
      insurance losses incurred by private health insurers.

PMID- 29177944
TI  - Ensuring more opportunity for robotics.

PMID- 29177943
TI  - Different autonomic responses to occupational and leisure time physical
      activities among blue-collar workers.
AB  - PURPOSE: The differential effect of occupational and leisure time physical
      activity on cardiovascular health is termed the physical activity health paradox.
      Cardiac autonomic modulation could bring insights about the underlying mechanism
      behind this differential effect. The aim was to compare heart rate variability
      (HRV) during different activities (sitting, standing and moving) at work and
      leisure among blue-collar workers. METHODS: One hundred thirty-eight workers from
      the NOMAD cohort were included. Data from physical activity and HRV were obtained
      for 3-4 days using tri-axial accelerometers (Actigraph GT3X+) and a heart rate
      monitor (Actiheart). HRV indices were determined during sitting, standing and
      moving both at work and leisure. Linear mixed-models with two fixed factors
      (activities and domains) were applied to investigate differences in HRV indices
      adjusting for individual and occupational factors. RESULTS: The results showed
      significant effects of domain (p < 0.01), physical activity type (p < 0.01) and
      interaction between domain and activity type (p < 0.01) on HRV indices. Mean
      heart rate (IBI) and parasympathetic measures of HRV (RMSSD and HF) were lower
      for sitting (p < 0.01) and higher for moving (p < 0.01) during work compared with
      leisure, while no difference between domains was found for standing (p > 0.05).
      Sympathovagal balance (LF/HF) was higher during work for sitting and moving (p <
      0.01), but showed no difference for standing (p = 0.62). CONCLUSIONS: Differences
      in cardiac autonomic modulation between work and leisure were found, indicating
      sympathetic predominance during work and parasympathetic predominance during
      leisure for sitting. Autonomic responses can be part of the mechanism that
      explains the differential effect of occupational and leisure time physical
      activity on health.

PMID- 29177945
TI  - Removing the urinary catheter on post-operative day 2 after robot-assisted
      laparoscopic radical prostatectomy: a feasibility study from a single high-volume
      referral centre.
AB  - The indwelling urinary catheter (UC) is a significant bother for men after
      radical prostatectomy (RP) and should be removed as soon as possible without
      jeopardizing the outcome. Our aim was to assess the feasibility and safety of its
      removal on postoperative day (POD) 2 after robot-assisted laparoscopic RP (RALP).
      A consecutive series of patients undergoing RALP for localized prostate cancer
      (PCa) were prospectively enrolled. Inclusion criteria were: no bladder-neck
      reconstruction, watertight urethrovesical anastomosis at 150 ml filling, <= 200
      ml of intraoperative bleeding, <= 80 ml of fluid from the drain on POD 1, clear
      urine from the UC on POD 2. Patients were discharged on POD 2. Continence was
      assessed at catheter removal and 1, 3 and 6 months after surgery. Urethrovesical
      anastomosis was performed with a standard technique on 3 layers. Sixty-six
      patients were enrolled. The UC was removed on POD 2 in all the cases and 96.4% of
      the patients were discharged on POD 2. Re-catheterization was needed 16 times and
      it was always performed easily. Twenty-four complications were reported by 20
      patients, mostly Clavien-Dindo (CD) grade II; 2 CD IIIB complications were
      observed. No anastomotic strictures were diagnosed. At catheter removal, 29% of
      the patients were completely continent, 41% at 1 month, 67% at 3 months and 92%
      at 6 months. In selected patients, removing the UC 48 h after RALP is feasible
      and safe and has no negative impact on continence if compared with the best
      international standards.

PMID- 29177946
TI  - Clinical outcomes after Ex-PRESS glaucoma shunt versus non-penetrating deep
      sclerectomy: two-year follow-up.
AB  - PURPOSE: To compare the two-year outcomes of non-penetrating deep sclerectomy
      (NPDS) and Ex-PRESS glaucoma shunt. METHODS: A retrospective chart review of
      patients who had undergone NPDS or Ex-PRESS since 2012 was conducted. Patients
      were excluded if they had undergone eye surgery other than cataract extraction,
      were diagnosed with ocular pathology other than glaucoma or had less than two
      year follow-up. Pre- and postoperative visual acuity, intraocular pressure (IOP),
      number of hypotensive drugs and visual fields were recorded, as well as intra-
      and postoperative complications. RESULTS: Thirty-nine eyes were included in the
      NPDS and twenty-three eyes in the Ex-PRESS group. There were no differences in
      baseline IOP and hypotensive drugs, IOP reduction or postoperative IOP-lowering
      medications between groups. Two years after surgery, IOP decrease compared to
      baseline was 23.5% with NPDS and 24.8% with Ex-PRESS. Qualified success (a 20%
      IOP reduction, with IOP <= 18 mmHg with or without medication) rates were
      similar: 53.8 and 69.6% for NPDS and Ex-PRESS. Visual fields progressed in four
      eyes of the NPDS (10.2%) and in three eyes (8.7%) of the Ex-PRESS group. As
      regards complications, early hypotony was more frequent after NPDS (9 eyes,
      23.1%) than Ex-PRESS (2 eyes, 8.7%), although the difference was not
      statistically significant. CONCLUSIONS: Both NPDS and Ex-PRESS produce an IOP
      lowering effect of approximately 25%. Success rates are similar after both
      procedures, and both seem to lead to a stabilization of visual loss.

PMID- 29177947
TI  - Effect of Lactobacillus rhamnosus on the response of Galleria mellonella against
      Staphylococcus aureus and Escherichia coli infections.
AB  - This study evaluated the prophylactic effects of the live or heat-killed
      probiotic strain Lactobacillus rhamnosus ATCC 7469 in Galleria mellonella,
      inoculated with Staphylococcus aureus or Escherichia coli. L. rhamnosus
      suspension was prepared and a part of it was autoclaved to obtain heat-killed
      lactobacilli. The larvae were inoculated of these suspensions and pathogenic. The
      survival of the larvae was observed during 7 days and after 24 h of inoculation
      haemocytes counted, melanization and nitric oxide production were analyzed.
      Larvae survival rate increased in the group inoculated with heat-killed L.
      rhamnosus, however, with no statistical difference. There was a significant
      increase in total haemocyte counts in all test groups. Haemolymph melanization
      and nitric oxide production were higher in the group inoculated with L. rhamnosus
      and infected with S. aureus. It was concluded that, in this model of infection,
      heat-killed L. rhamnosus ATCC 7469 promoted greater protection in Galleria
      mellonella infected with S. aureus or E. coli.

PMID- 29177948
TI  - Increased serum amyloid A in nasal polyps is associated with systemic
      corticosteroid insensitivity in patients with chronic rhinosinusitis with nasal
      polyps: a pilot study.
AB  - BACKGROUND: Serum amyloid A (SAA) was involved in the pathogenesis of
      glucocorticoid resistance in lung diseases. However, their association with
      systemic corticosteroid insensitivity in chronic rhinosinusitis with nasal polyps
      (CRSwNP) patients remains to be assessed. METHODS: This study enrolled 32 CRSwNP
      patients to evaluate the association between SAA expression in NP and
      corticosteroid insensitivity, and the value of polyp SAA level for predicting the
      response to oral corticosteroids in CRSwNP patients. All patients were given a
      course of oral prednisone (30 mg daily for 2 weeks) and subdivided into
      glucocorticoid(GC)-sensitive and -insensitive subgroup according to the change in
      polyp size scores. The polyp specimens were obtained before and after
      corticosteroid treatment. SAA levels in polyp tissues were evaluated by enzyme
      linked immunosorbent assay and quantitative reverse transcription polymerase
      chain reaction. Regression analysis was performed to analyze the association
      between SAA protein levels and corticosteroid insensitivity. RESULTS: 13/32
      (40.62%) CRSwNP patients were insensitive to the oral corticosteroid therapy. SAA
      mRNA and protein levels were significantly increased in GC-insensitive NP
      compared to those in GC-sensitive NP. Tissue SAA protein levels were positively
      correlated with tissue neutrophil numbers. Regression analysis revealed tissue
      SAA levels were significantly correlated with corticosteroid insensitivity (P <
      0.01). ROC curves indicated that the area under the curve was 0.87. When the
      polyp SAA protein level was 122.2 ng/ml or higher, the sensitivity and
      specificity were 76.92 and 73.68%, respectively. CONCLUSIONS: Our findings
      suggest that increased SAA in NP is associated with reduced response to oral
      corticosteroids in CRSwNP. SAA levels in NP may have potential value in
      predicting corticosteroid insensitivity in CRSwNP patients.

PMID- 29177950
TI  - Vascular and Tissue Changes of Magnetic Susceptibility in the Mouse Brain After
      Transient Cerebral Ischemia.
AB  - Quantitative susceptibility mapping (QSM) has been recently introduced as a novel
      MRI post-processing technique of gradient recalled echo (GRE) data. QSM is useful
      in depicting both brain anatomy and for detecting abnormalities. Its utility in
      the context of ischemic stroke has, however, not been extensively characterized
      so far. In this study, we explored the potential of QSM to characterize vascular
      and tissue changes in the transient middle cerebral artery occlusion (tMCAO)
      mouse model of cerebral ischemia. We acquired GRE data of mice brains at
      different time points after tMCAO, from which we computed QSM and MR frequency
      maps, and compared these maps with diffusion imaging and multi-slice multi-echo
      imaging data acquired in the same animals. Prominent vessels with increased
      magnetic susceptibility were visible surrounding the lesion on both frequency and
      magnetic susceptibility maps at all time points (mostly visible at > 12 h after
      reperfusion). Immunohistochemistry revealed the presence of compressed
      capillaries and dilated larger vessels, suggesting that the appearance of
      prominent vessels after reestablishment of reperfusion may serve compensatory
      purposes. In addition, on both contrast maps, tissue regions of decreased
      magnetic susceptibility were observed at 24 and 48 h after reperfusion that were
      distinctly different from the lesions seen on maps of the apparent diffusion
      coefficient and T 2 relaxation time constant. Since QSM can be extracted as an
      add-on from GRE data and thus requires no additional acquisition time in the
      course of acute stroke MRI examination, it may provide unique and complementary
      information during the course of acute stroke MRI examinations.

PMID- 29177951
TI  - Posterolateral overhang affects patient quality of life after total knee
      arthroplasty.
AB  - PURPOSE: To investigate the appropriate mediolateral placement of symmetrical
      tibial components and the amount of overhang expected from the posterolateral of
      tibial components implanted to give ideal coverage and the subsequent incidence
      of residual knee pain and reduction in functional capacity. METHOD: A
      retrospective evaluation was made of 146 consecutive total knee arthroplasties.
      The posterolateral overhang, rotational alignment and coverage of the tibial
      component were measured on a post-operative CT scan and the effect of
      posterolateral overhang on clinical outcomes was analysed 3 years after surgery.
      RESULTS: Complaints of local pain in the posterolateral corner were determined in
      76 (52.1%) patients. At the Posterolateral corner, overhang was determined in 111
      (76%) patients, in the cortical border in 11 (7.6%) patients and underhang in 24
      (16.4%) patients. In 71 (48.6%) patients, pain was determined together with
      oversize and in the evaluation of the overhang of the tibial component in the
      posterolateral region and the rotation status, there was determined to be
      overhang in 75 (96.2%) patients where the tibial component was placed in ideal
      rotation, in 25 (100%) where placement was in external rotation and in 11 (25.6%)
      where placement was in internal rotation. The mean KSS, KSS-F and WOMAC-P scores
      were 83.9 +/- 6.3, 83.3 +/- 7.8 and 4.6 +/- 2.9, respectively, in those with
      posterolateral overhang of the tibial component .The mean KSS, KSS-F and WOMAC-P
      scores were 86.6 +/- 8.4, 89.5 +/- 7.8 and 2.8 +/- 2.1, respectively, in those
      with no overhang and the difference was determined to be statistically
      significant. The amount of overhang was determined as mean 3.6 +/- 2.0 mm in
      those with posterolateral pain and 0.02 +/- 3.4 mm in those without pain and the
      difference was statistically significant. CONCLUSIONS: This study demonstrated
      that overhang in the posterolateral region is surprisingly high and negatively
      affects the clinical results following TKA, thereby presenting a danger to the
      success of TKA. The risk of posterolateral oversizing can increase with placement
      of the tibial component in external rotation.

PMID- 29177949
TI  - Prognostic value of CD45 transcriptional expression in head and neck cancer.
AB  - INTRODUCTION: Tumor-infiltrating lymphocytes (TILs) have a recognized antitumor
      activity in head and neck squamous cell carcinoma (HNSCC). CD45 is one of the
      most highly expressed proteins in lymphocytes. We carry out a study to assess the
      prognostic value of transcriptional expression of CD45 in HNSCC. MATERIAL AND
      METHODS: We determined the transcriptional expression of CD45 in 160 consecutive
      HNSCC patients and compared the TIL values according to the CD45 expression.
      RESULTS: Five-year disease-free survival for patients with a high transcriptional
      expression of CD45 (n = 107) was 62.4% and for patients with a low expression (n
      = 53) it was 36.2% (P = 0.003). Patients with a high expression of CD45 had a
      better local recurrence-free survival and disease-specific survival. The results
      of a multivariate analysis showed that patients with a low expression of CD45 had
      2.0-fold high risk of recurrence (95% CI 1.2-3.2, P = 0.003). In oropharyngeal
      carcinomas, HPV-positive tumors showed a higher transcriptional CD45 expression
      than HPV-negative tumors. Tumors with high CD45 expression had
      immunohistochemical TIL scores significantly higher than those with low CD45
      expression. CONCLUSION: According to our results, CD45 expression is a potential
      marker for tumor outcome in HNSCC patients.

PMID- 29177952
TI  - Distribution and phylogeny of Hyalomma ticks (Acari: Ixodidae) in Turkey.
AB  - The genus Hyalomma includes some of the most medically and veterinarily important
      tick species in the world. To clarify and identify the current distribution of
      the species of Hyalomma, field studies were conducted in 65 localities in Turkey
      and five localities in Cyprus. Additionally, using mitochondrial 12S and 16S
      ribosomal DNA, specimens of Hyalomma from Turkey, H. excavatum from Cyprus, H.
      marginatum from Spain and Italy were evaluated together with the available
      sequences obtained from Genbank. Morphological and molecular analyses
      demonstrated the presence of four species in Turkey: H. marginatum, H. excavatum,
      H. aegyptium and H. asiaticum. Hyalomma marginatum is the dominant species in the
      Central and Northern parts of Turkey, whereas H. excavatum distributes mostly in
      the Southern parts. Hyalomma asiaticum is restricted to the Southeastern
      Anatolia. However, some sympatric regions were observed for these species.
      Phylogenetic trees obtained with Maximum Likelihood method demonstrated five
      clades. Data supported previous conclusions, but placed H. asiaticum, H.
      scupense, H. dromedarii and H. aegyptium in different clades with high bootstrap
      values. Specimens of H. anatolicum group and H. marginatum complex are sister
      groups. Pairwise distance analyses of these groups showed 2.8 and 3% differences
      for 12S rDNA and 16S rDNA, respectively. Therefore, additional analyses with the
      samples from different locations using different markers need to evaluate the
      exact status of the species of these groups.

PMID- 29177953
TI  - Phase II Study of Gemcitabine Plus Sirolimus in Previously Treated Patients with
      Advanced Soft-Tissue Sarcoma: a Spanish Group for Research on Sarcomas (GEIS)
      Study.
AB  - BACKGROUND: Gemcitabine plus sirolimus enhances apoptosis in vitro and increases
      anti-tumor efficacy in vivo in soft-tissue sarcoma (STS) models. OBJECTIVE: The
      objective of this study was to evaluate the activity and toxicity of the
      combination of gemcitabine plus sirolimus in patients with STS after failure of
      standard chemotherapy. PATIENTS AND METHODS: Advanced STS patients, previously
      treated with doxorubicin and/or ifosfamide, were included in this single-arm
      phase II study. Patients received gemcitabine 800 mg/m2 intravenously (iv) at 10
      mg/m2/min on days 1 and 8 every 3 weeks plus sirolimus 5 mg daily orally (po).
      After enrolment of the first 12 patients, the study protocol was amended due to
      toxicity and the starting dose of sirolimus was reduced to 3 mg daily po.
      Archival tumor samples were analyzed for extracellular signal-regulated kinase 1
      and 2 (ERK1/2) expression and correlated with outcome. The primary endpoint was
      progression-free rate (PFR) at 3 months. RESULTS: From May 2012 to May 2013, 28
      patients were enrolled at eight centers. PFR at 3 and 6 months was 44% and 20%,
      respectively, with 12 patients being free of progression at 3 months. Median
      progression-free survival (PFS) was 1.85 months (95% confidence interval [CI]
      0.73-2.97) and median overall survival (OS) was 9.2 months (95% CI 5.8-12.5). No
      responses were observed. The most common grade 3-4 hematologic toxicities were
      neutropenia (48%) and leukopenia (41%) and the most frequent grade 3 non
      hematologic toxicities were infection (18.5%), transaminitis (15%), fatigue
      (11%), and pneumonitis (11%). ERK1/2 expression was significantly correlated with
      PFS (p = 0.026). CONCLUSIONS: The combination of gemcitabine and sirolimus is an
      active treatment in STS. Further investigation is warranted. ClinicalTrials.gov
      identifier: NCT01684449.

PMID- 29177954
TI  - Pharmacogenetic study of the impact of ABCB1 single-nucleotide polymorphisms on
      lenalidomide treatment outcomes in patients with multiple myeloma: results from a
      phase IV observational study and subsequent phase II clinical trial.
AB  - PURPOSE: Despite therapeutic advances, patients with multiple myeloma (MM)
      continue to experience disease relapse and treatment resistance. The gene ABCB1
      encodes the drug transporter P-glycoprotein, which confers resistance through
      drug extrusion across the cell membrane. Lenalidomide (Len) is excreted mainly
      via the kidneys, and, given the expression of P-gp in the renal tubuli, single
      nucleotide polymorphisms (SNPs) in the ABCB1 gene may influence Len plasma
      concentrations and, subsequently, the outcome of treatment. We, therefore,
      investigated the influence of ABCB1 genetic variants on Len treatment outcomes
      and adverse events (AEs). METHODS: Ninety patients with relapsed or refractory
      MM, who received the second-line Len plus dexamethasone in the Rev II trial, were
      genotyped for the ABCB1 SNPs 1199G>A (Ser400Asn, rs2229109), 1236C>T (silent,
      rs1128503), 2677G>T/A (Ala893Ser, rs2032582), and 3435C>T (silent, rs1045642)
      using pyrosequencing, and correlations to response parameters, outcomes, and AEs
      were investigated. RESULTS: No significant associations were found between
      genotype and either best response rates or hematological AEs, and 1236C>T,
      2677G>T or 3435C>T genotypes had no impact on survival. There was a trend towards
      increased time to progression (TTP) in patients carrying the 1199A variant, and a
      significant difference in TTP between genotypes in patients with standard-risk
      cytogenetics. CONCLUSIONS: Our findings show a limited influence of ABCB1
      genotype on lenalidomide treatment efficacy and safety. The results suggest that
      1199G>A may be a marker of TTP following Len treatment in standard-risk patients;
      however, larger studies are needed to validate and clarify the relationship.

PMID- 29177955
TI  - A randomized, double-blind, placebo-controlled, proof-of-concept trial of
      creatine monohydrate as adjunctive treatment for bipolar depression.
AB  - Depressive episodes are a major cause of morbidity and dysfunction in individuals
      suffering from bipolar disorder. Currently available treatments for this
      condition have limited efficacy and new therapeutic options are needed. Extensive
      research in the pathophysiology of bipolar disorder points to the existence of
      mitochondrial and bioenergetic dysfunction. We hypothesized that creatine
      monohydrate, a nutraceutical that works as a mitochondrial modulator, would be
      effective as an adjunctive therapy for bipolar depression. We conducted a double
      blind trial in which 35 patients with bipolar disorder type I or II in a
      depressive episode by DSM-IV criteria and in use of regular medication for the
      treatment of this phase of the disease were randomly allocated into two
      adjunctive treatment groups for 6 weeks: creatine monohydrate 6 g daily (N = 17)
      or placebo (N = 18). Primary efficacy was assessed by the change in the
      Montgomery-Asberg Depression Rating Scale (MADRS). We did not find a
      statistically significant difference in the comparison between groups for the
      change in score on the MADRS after 6 weeks in an intention-to-treat (ITT)
      analysis (p = 0.560; Cohen's d = 0.231). However, we found significant
      superiority of creatine add-on vs. placebo when we considered the remission
      criterion of a MADRS score <= 12 at week 6 analyzing the outcome of the 35
      randomized patients on ITT (52.9% remission in the creatine group vs. 11.1%
      remission in the placebo group) and of the 23 completers (66.7% remission in the
      creatine group vs. 18.2% remission in the placebo group) (p = 0.012; OR = 9.0 and
      p = 0.036; OR = 9.0, respectively). Two patients who received creatine switched
      to hypomania/mania early in the trial. No clinically relevant physical side
      effects were reported or observed. This proof-of-concept study, aiming to restore
      brain bioenergetics using an adjunctive mitochondrial modulator, is not
      conclusive on the efficacy of creatine add-on for bipolar depression, but
      suggests that this compound may have a role in the adjunctive treatment of this
      phase of the illness. Further investigation through randomized controlled trials
      with larger samples should be conducted to verify the efficacy of creatine
      supplementation for bipolar depression and also for subsyndromal depressive
      symptoms.

PMID- 29177956
TI  - Urgency to Assess the Health Impact of Ambient Air Pollution in China.
AB  - As the world's second-largest economy, China is going on suffering from
      environmental pollution, especially for ambient air pollution, which has become a
      major threat to public health; public awareness of the detrimental effects of air
      pollution on health is increasing-particularly in relation to haze days.
      Considering the nonlinear relationship of ambient air pollution exposure and
      health impacts, and the differences in specific sources of air pollution with
      those in North America and Europe, conducting health impact assessments of
      ambient air pollution in China has thus become an urgent task for public health
      practitioners. Systematic review of the health effects of exposure to ambient air
      pollution from quantitative studies conducted in Chinese could provide vital
      information for epidemiology-based health impact assessments and the
      implementation of a national environmental protection policy.

PMID- 29177957
TI  - Characteristics of Major Air Pollutants in China.
AB  - Following the rapid development of China's economy, air pollution has become more
      and more serious. Air pollution in China presents complex pollution characterized
      by high PM2.5 and O3 concentration. This study presents an overview of the status
      of air quality and emission in China and discusses the temporal and spatial
      distribution of major pollutants (PM10, PM2.5, SO2, NOX, and O3). The results
      show that the reduced emissions have improved the air quality in China. However,
      the Chinese National Ambient Air Quality Standard (CNAAQS) for PM10 and PM2.5
      still be exceeded in many cities of China in 2015. A total of 77.5% (for PM2.5)
      and 65.4% (for PM10) of the monitoring cities were found to be exceeded CNAAQS.
      The average annual O3 concentration was increasing during 2013-2015, and 16% of
      the total cities in 2015 did not meet the CNAAQS, indicating that O3 pollution
      should be paid more attention. For NO2 and SO2, the exceedances of CNAAQS are
      rare. PM2.5, PM10, and SO2 concentrations are higher in northern than in southern
      regions. High NO2 occurred in Beijing-Tianjin-Hebei and Yangtze River delta
      region. Secondary particles formation and motor vehicle exhaust were the main
      sources of PM2.5 in megacities. Dust was the main source for PM10. The formation
      of O3 is VOC-limited in urban areas of China and NOX-limited in nonurban areas.

PMID- 29177958
TI  - Human Exposure Assessment for Air Pollution.
AB  - Assessment of human exposure to air pollution is a fundamental part of the more
      general process of health risk assessment. The measurement methods for exposure
      assessment now include personal exposure monitoring, indoor-outdoor sampling,
      mobile monitoring, and exposure assessment modeling (such as proximity models,
      interpolation model, air dispersion models, and land-use regression (LUR)
      models). Among these methods, personal exposure measurement is considered to be
      the most accurate method of pollutant exposure assessment until now, since it can
      better quantify observed differences and better reflect exposure among smaller
      groups of people at ground level. And since the great differences of geographical
      environment, source distribution, pollution characteristics, economic conditions,
      and living habits, there is a wide range of differences between indoor, outdoor,
      and individual air pollution exposure in different regions of China. In general,
      the indoor particles in most Chinese families comprise infiltrated outdoor
      particles, particles generated indoors, and a few secondary organic aerosol
      particles, and in most cases, outdoor particle pollution concentrations are a
      major contributor to indoor concentrations in China. Furthermore, since the time,
      energy, and expense are limited, it is difficult to measure the concentration of
      pollutants for each individual. In recent years, obtaining the concentration of
      air pollutants by using a variety of exposure assessment models is becoming a
      main method which could solve the problem of the increasing number of individuals
      in epidemiology studies.

PMID- 29177959
TI  - Ambient Air Pollution and Biomarkers of Health Effect.
AB  - Recently, the air pollution situation of our country is very serious along with
      the development of urbanization and industrialization. Studies indicate that the
      exposure of air pollution can cause a rise of incidence and mortality of many
      diseases, such as chronic obstructive pulmonary disease (COPD), asthma,
      myocardial infarction, and so on. However, there is now growing evidence showing
      that significant air pollution exposures are associated with early biomarkers in
      various systems of the body. In order to better prevent and control the damage
      effect of air pollution, this article summarizes comprehensively epidemiological
      studies about the bad effects on the biomarkers of respiratory system,
      cardiovascular system, and genetic and epigenetic system exposure to ambient air
      pollution.

PMID- 29177960
TI  - Air Pollution and Mortality in China.
AB  - Ambient air pollution has been an important environmental issue in most areas of
      China. This chapter summarized the mortality effects of short-term and long-term
      exposures to various air pollutants among Chinese population. The literature
      review identified sufficient information to support significant short-term
      mortality effects of various air pollutants from time series analyses and case
      crossover studies, such as PM10, PM2.5, SO2, NO2, and O3. On the other hand,
      though the literature review suggested a positive effect of long-term exposure to
      air pollution on mortality and lung cancer risk, the evidence has been limited
      among Chinese population, indicating that more studies, especially cohort
      studies, are warranted.

PMID- 29177961
TI  - Ambient Air Pollution and Morbidity in Chinese.
AB  - The rapid economic growth in China is coupled with a severe ambient air
      pollution, which poses a huge threat to human health and the sustainable
      development of social economy. The rapid urbanization and industrialization over
      the last three decades have placed China as one of countries with the greatest
      disease burden in world. Notably, the prevalence rate of chronic noncommunicable
      diseases (CND), including respiratory diseases, CVD, and stroke, in 2010 reaches
      16.9%. The continuous growth of the incidence of CND urgent needs for effective
      regulatory action for health protection. This study aims to evaluate the impact
      of rapid urbanization on status of ambient air pollution and associated adverse
      health effects on the incidence and the burden of CND and risk assessment. Our
      findings would be greatly significant in the prediction of the risk of ambient
      air pollution on CND and for evidence-based policy making and risk management in
      China.

PMID- 29177962
TI  - Air Pollution and Children's Health in Chinese.
AB  - Children can be considered as a high-risk population to environmental stress
      since some of the organ systems including the immune system and respiratory
      system are still in development during childhood. During childhood, the impact of
      environmental pollutants exposure may program child growth and development that
      have long-term consequences on later health and disease risk. Considering the
      rapid economic growth in recent decades in China, the impact of ambient air
      pollution on children health causes concerns. Therefore, we aimed to review the
      current epidemiological evidence on the effects of air pollution exposure on
      adverse health outcome, including respiratory diseases, lung function, high blood
      pressure, cognitive disorder, and obesity in childhood in China. We believe that
      the findings summarized in our review demonstrate an unequivocal relationship
      between air pollutants exposure and Chinese children health and these results
      have large public health influences.

PMID- 29177963
TI  - The Associations Between Air Pollution and Adverse Pregnancy Outcomes in China.
AB  - Research on the potential impact of air pollution on the human's health has
      increased rapidly in recent years. Several studies have suggested that exposure
      to air pollutants during period of pregnancy which is a crucial time point of
      mother-fetus development may have long-term and serious impact on adverse
      pregnancy outcomes. There is lack of review to evaluate the existed epidemiologic
      evidence on the associations between air pollutants and adverse pregnancy
      outcomes in China, so we conducted a review to explore the current
      epidemiological evidence on the effects of air pollutants to pregnancy outcomes
      and possible mechanisms during the pregnancy process. We used keywords to
      systematically search all the English and Chinese literatures on studies that
      were conducted in China. Exposure to air pollutants during pregnancy had shown
      there were harmful effects for different birth outcomes: preterm birth, low birth
      weight, stillbirth, birth defects, infertility, and macrosomia fetus. Results on
      the effects of air pollutants on adverse pregnancy outcomes are small and
      inconsistent because they vary in their design and methodology. The existed
      available evidence is compatible with either a small negative effect of air
      pollutants on pregnancy outcomes or with no effect; therefore, further studies
      are needed to confirm and quantify the possible associations and potential
      biologic mechanisms between air pollutants and pregnancy outcomes.

PMID- 29177964
TI  - Comparison of Health Impact of Air Pollution Between China and Other Countries.
AB  - Air pollution is the world's largest single environmental risk according to the
      World Health Organization (WHO), which caused around seven million deaths in
      2012. Extensive epidemiological studies have been carried out worldwide to
      examine the health impacts of ambient air pollution, consistently demonstrating
      significant health impacts of ambient air pollution. Air pollution problem in
      China is especially serious; it has become the fourth biggest threat to the
      health of the Chinese people. In this review, we summarized existing literature,
      compared health impact of air pollution between China and other countries, and
      found substantial heterogeneity in the risk estimates of air pollution. The
      effect heterogeneities may be due to the differences in the characteristics of
      populations (e.g., the proportion of the elder population and people with
      preexisting diseases), exposure profile (e.g., air pollution concentrations and
      composition), and regional climate. Although the magnitude of relative risk
      estimates of air pollution is generally similar with that in other parts of the
      world, air pollution is one of China's most serious environmental health problems
      given the huge number of people exposed to high concentration levels of air
      pollution in China.

PMID- 29177965
TI  - Air Pollution, Disease Burden, and Health Economic Loss in China.
AB  - As the largest developing country in the world, China is now facing one of the
      severest air pollution problems. The objective of this section is to evaluate the
      disease burden and corresponding economic loss attributable to ambient air
      pollution in China. We reviewed a series of studies by Chinese or foreign
      investigators focusing on the disease burden and economic loss in China. These
      studies showed both the general air pollution and haze episodes have resulted in
      substantial disease burden in terms of excess number of premature deaths,
      disability-adjusted life-year loss, and years of life lost. The corresponding
      economic loss has accounted for an appreciable proportion of China's national
      economy. Overall, the disease burden and health economic loss due to ambient air
      pollution in China is greater than in the remaining parts of the world, for one
      of the highest levels of air pollution and the largest size of exposed
      population. Consideration of both health and economic impacts of air pollution
      can facilitate the Chinese government to develop environmental policies to reduce
      the emissions of various air pollutants and protect the public health.

PMID- 29177966
TI  - Air Pollution Prevention and Control Policy in China.
AB  - With rapid urbanization and development of transport infrastructure, air
      pollution caused by multiple-pollutant emissions and vehicle exhaust has been
      aggravated year by year in China. In order to improve air quality, the Chinese
      authorities have taken a series of actions to control air pollution emission load
      within a permissible range. However, although China has made positive progress on
      tackling air pollution, these actions have not kept up with its economy growth
      and fossil-fuel use. The traditional single-pollutant approach is far from enough
      in China now, and in the near future, air pollution control strategies should
      move in the direction of the multiple-pollutant approach. In addition,
      undesirable air quality is usually linked with the combination of high emissions
      and adverse weather conditions. However, few studies have been done on the
      influence of climate change on atmospheric chemistry in the global perspective.
      Available evidence suggested that climate change is likely to exacerbate certain
      kinds of air pollutants including ozone and smoke from wildfires. This has become
      a major public health problem because the interactions of global climate change,
      urban heat islands, and air pollution have adverse effects on human health. In
      this chapter, we first review the past and current circumstances of China's
      responses to air pollution. Then we discuss the control challenges and future
      options for a better air quality in China. Finally, we begin to unravel links
      between air pollution and climate change, providing new opportunities for
      integrated research and actions in China.

PMID- 29177967
TI  - Perspective for Future Research Direction About Health Impact of Ambient Air
      Pollution in China.
AB  - Air pollution has become one of the major risks to human health because of the
      progressive increase in the use of vehicles powered by fossil fuels. Although
      lots of works on the health impact of ambient air pollution have been done in
      China, the following recommendations for future research were identified in this
      chapter: (1) the synergistic effect of indoor air pollution with climate change;
      (2) develop new technologies to improve accurate assessment of air pollution
      exposure; (3) well-designed cohort study of sensitive populations including
      children, older people, and people with chronic health problems; (4) multi-omics
      technologies in the underlying mechanisms study; and (5) benefits evaluation of
      improvement of air quality. In conclusion, China is becoming a suitable study
      site, providing an ideal opportunity to evaluate the effects of environmental
      pollution, including air pollution, on human health, which might serve as an
      example for developing countries where health impacts of air pollution are as
      serious as in China.

PMID- 29177968
TI  - Microscopic characterization of orchid mycorrhizal fungi: Scleroderma as a
      putative novel orchid mycorrhizal fungus of Vanilla in different crop systems.
AB  - Vanilla is an orchid of economic importance widely cultivated in tropical regions
      and native to Mexico. We sampled three species of Vanilla (V. planifolia, V.
      pompona, and V. insignis) in different crop systems. We studied the effect of
      crop system on the abundance, type of fungi, and quality of pelotons found in the
      roots using light and electron microscopy and direct sequencing of mycorrhizal
      structures. Fungi were identified directly from pelotons obtained from
      terrestrial roots of vanilla plants in the flowering stage. Root samples were
      collected from plants in crop systems located in the Totonacapan area in Mexico
      (states of Puebla and Veracruz). DNA was extracted directly from 40 pelotons and
      amplified using ITS rRNA sequencing. Peloton-like structures were observed,
      presenting a combination of active pelotons characterized by abundant hyphal
      coils and pelotons in various stages of degradation. The most active pelotons
      were observed in crop systems throughout living tutors (host tree) in comparison
      with roots collected from dead or artificial tutors. Fungi identified directly
      from pelotons included Scleroderma areolatum, a common ectomycorrhizal fungus
      that has not been reported as a mycorrhizal symbiont in orchids. Direct
      amplification of pelotons also yielded common plant pathogens, including Fusarium
      and Pyrenophora seminiperda, especially in those sites with low colonization
      rates, and where large numbers of degraded pelotons were observed. This research
      reports for the first time the potential colonization of Vanilla by Scleroderma,
      as a putative orchid mycorrhizal symbiont in four sites in Mexico and the
      influence of crop system on mycorrhizal colonization on this orchid.

PMID- 29177969
TI  - The effect of methamphetamine exposure during pregnancy and lactation on
      hippocampal doublecortin expression, learning and memory of rat offspring.
AB  - The aim of this study was to evaluate the effect of methamphetamine (MA) exposure
      during pregnancy and lactation on doublecortin (DCX) expression in the
      hippocampus of rat offspring and also on learning/memory. Thirty-five pregnant
      Wistar rats were randomly divided into seven groups of 5 rats each: three
      experimental groups, each receiving 5 mg/kg body weight (BW) intraperitoneal
      (i.p.) injections of MA during pregnancy or/and lactation; three sham groups,
      each receiving saline injections; one control group, receiving no injection.
      After the interventions, two male pups (1 and 22 days old) were randomly selected
      from each mother, sacrificed and their brains subjected to DCX
      immunohistochemistry. One additional male pup from each mother was randomly
      selected and maintained for 60 days for testing in the Morris water maze and
      passive avoidance tests. MA administration during pregnancy was found to have
      significantly decreased the number of DCX-positive cells in the CA1, CA3 and DG
      regions of the hippocampus in the 1-day pups (P <= 0.05) and to have
      significantly decreased the number of DCX-positive cells in only two regions of
      the hippocampus, the CA1 and DG regions, in 22-day old pups. In comparison,
      exposure to MA during lactation was only associated with a significant decrease
      in the number of DCX-positive cells in the DG. Exposure to MA during pregnancy
      had significant impact on the intensity of DCX expression in the hippocampus of 1
      and 22-day pups (P <= 0.05). There was no significant difference in
      memory/learning among the study groups. Our results indicate the administration
      of MA during pregnancy had a greater effect that during the lactation period on
      DCX expression in the hippocampus of rat offspring.

PMID- 29177971
TI  - Organic Ion Transporters and Statin Drug Interactions.
AB  - PURPOSE OF REVIEW: Statin drug-drug interactions (DDIs) are both troublesome to
      patients as well as costly to medical resources. The ability to predict and avoid
      these events could lead to improved outcomes as well as patient satisfaction.
      This review will explore efforts to better understand and predict these
      interactions specifically related to one drug transport system, the organic anion
      transporting polypeptides (OATPs) specifically OATP1B1 and OATP1B3. RECENT
      FINDINGS: Since the publication of the discovery of OATPs, there have been
      various pharmacokinetic models that have been proposed to explain the variation
      in pharmacokinetic and clinical effects related to the OATPs. The effects in
      transport activity appear to be partially related to the individual polymorphisms
      studied. Drug-drug interactions can occur when other drugs compete for the
      metabolic site on the OATPs. Various medications are identified as substrates
      and/or inhibitors of the OATPs, thereby complicating the ability to fully predict
      the impact on levels and effects. All of the models reviewed claim successes but
      show limited clinical utility. There are specific populations that have been
      identified, predominately various Asian descendants that require lower doses of
      statins to avoid adverse events. The concept of attributing these actions to the
      OATPs has been explored, but current models cannot accurately predict statin
      blood levels or elimination constants. The current research only points to the
      differences in the human genome and the single-nucleotide polymorphisms that
      exist between us. Based upon the currently available studies, there is beginning
      to be a glimmer in the understanding how different populations respond to statin
      transport and elimination. Additionally and unfortunately, there are other
      enzymes to be studied to better predict patient differences. Clearly, there has
      been much work completed, yet many more questions require answering to better
      understand these transport proteins.

PMID- 29177970
TI  - Feeding on different attractive flowering plants affects the energy reserves of
      Culex pipiens pallens adults.
AB  - Mosquito adults usually need to ingest sugar from nectar host plants to sustain
      their metabolic needs. Mosquitoes could be differentially attracted by various
      flowering plant species, and the volatiles were thought to be important factors
      attributed to the differential attractiveness. However, whether mosquitoes'
      preference for host plants correlates with their nutritional rewards from sugar
      sources remains unclear. In the present study, the preference of newly emerged
      Culex pipiens pallens to three kinds of flowering plants (Ligustrum quihoui,
      Abelia chinensis, and Nerium indicum) was determined in the olfactometer.
      Besides, when the newly emerged mosquitoes were provided with these flowering
      plants as sugar sources, the content of their metabolic reserves (glycogen,
      lipid, and protein) was determined. The results revealed that Cx. pipiens pallens
      could be differentially attracted by the odors emitted by the inflorescences of
      the tested flowering plants, and the nutritional rewards of mosquitoes were
      significantly affected by feeding on different inflorescences. The present study
      demonstrated that feeding on nectar host plants with differential attraction
      could affect the energy reserves of Cx. pipiens pallens.

PMID- 29177972
TI  - Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding
      Adrenodoxin Reductase-A Ubiquitous Enzyme.
AB  - FAD and NAD(P) together represent an ideal pair for coupled redox reactions in
      their capacity to accept two electrons and their redox potentials. Enzymes that
      bind both NAD(P) and FAD represent large superfamilies that fulfill essential
      roles in numerous metabolic pathways. Adrenodoxin reductase (AdxR) shares
      Rossmann fold features with some of these superfamilies but remains in a group of
      its own in the absence of sequence homology. This article documents the
      phylogenetic distribution of AdxR by examining whole genome databases for
      Metazoa, Plantae, Fungi, and Protista, and determines the conserved structural
      features of AdxR. Scanning these databases showed that most organisms have a
      single gene coding for an AdxR ortholog. The sequence identity between AdxR
      orthologs is correlated with the phylogenetic distance among metazoan species.
      The NADP binding site of all AdxR orthologs showed a modified Rossmann fold motif
      with a GxGxxA consensus instead of the classical GxGxxG at the edge of the first
      betaalpha-fold. To examine the hypothesis that enzyme-coenzyme interfaces
      represent the conserved regions of AdxR, the residues interfacing FAD and NADP
      were identified and compared with multiple-sequence alignment results. Most
      conserved residues were indeed found at sites that surround the interfacing
      residues between the enzyme and the two coenzymes. In contrast to protein-protein
      interaction hot-spots that may appear in isolated patches, in AdxR the conserved
      regions show strict preservation of the overall structure. This structure
      maintains the precise positioning of the two coenzymes for optimal electron
      transfer between NADP and FAD without electron leakage to other acceptors.

PMID- 29177974
TI  - Antitumor activity of raloxifene-targeted poly(styrene maleic acid)-poly (amide
      ether-ester-imide) co-polymeric nanomicelles loaded with docetaxel in breast
      cancer-bearing mice.
AB  - Purpose Raloxifene (RA) receptors have over-expressed GPER-positive breast cancer
      tumors. The purpose of this work was to evaluate the antitumor activity and
      pharmacokinetic behavior of docetaxel (DTX), loaded in RA-targeted nanomicelles,
      which were designed to overcome a lack of specific distribution and inadequate
      DTX concentration in tumor tissues, as well as its cytotoxicity and damage to
      normal tissues. Methods DTX-loaded RA-targeted poly(styrene maleic acid) (SMA)-
      poly(amide-ether-esterimide)-poly(ethylene glycol) (PAEEI-PEG) nanomicelles were
      prepared; then, their antitumor activity and survival rate were studied in MC4-L2
      tumors induced in BALB/c mice. The pharmacokinetics of DTX-loaded SMA-PAEEI-PEG
      RA micelles was also investigated in comparison with free DTX. Results DTX-loaded
      SMA-PAEEI-PEG-RA micelles inhibited tumor growth considerably and increased
      animal survival as compared to free DTX and non-targeted micelles. SMA-PAEEIPEG
      RA micelles enhanced significantly the area under the curve (AUC0-infinity) 1.3
      times as compared to free DTX and reduced clearance (CL) from 410.43 ml/kg.h (for
      free DTX) to 308.8 ml/kg.h (for SMA-PAEEI-PEG-RA micelles). Volume of
      distribution (Vdss) was also reduced 1.4 times as compared to free DTX. RA
      targeted micelles increased tumor inhibition rate (TIR) 1.3 times and median
      survival time (MST) >1.5 times compared to free DTX. Percentage increase in life
      span (%ILS) was also enhanced significantly from 41.66% to >83.33% in MC4-L2
      tumor-bearing BALB/c mice. Discussion All studies in this work showed the
      potential of DTX-loaded SMA-PAEEI-PEG-RA micelles in the treatment of GPER
      positive receptor breast cancer tumors.

PMID- 29177973
TI  - Phylogenetic Profiling of Mitochondrial Proteins and Integration Analysis of
      Bacterial Transcription Units Suggest Evolution of F1Fo ATP Synthase from
      Multiple Modules.
AB  - ATP synthase is a complex universal enzyme responsible for ATP synthesis across
      all kingdoms of life. The F-type ATP synthase has been suggested to have evolved
      from two functionally independent, catalytic (F1) and membrane bound (Fo),
      ancestral modules. While the modular evolution of the synthase is supported by
      studies indicating independent assembly of the two subunits, the presence of
      intermediate assembly products suggests a more complex evolutionary process. We
      analyzed the phylogenetic profiles of the human mitochondrial proteins and
      bacterial transcription units to gain additional insight into the evolution of
      the F-type ATP synthase complex. In this study, we report the presence of
      intermediary modules based on the phylogenetic profiles of the human
      mitochondrial proteins. The two main intermediary modules comprise the
      alpha3beta3 hexamer in the F1 and the c-subunit ring in the Fo. A comprehensive
      analysis of bacterial transcription units of F1Fo ATP synthase revealed that
      while a long and constant order of F1Fo ATP synthase genes exists in a majority
      of bacterial genomes, highly conserved combinations of separate transcription
      units are present among certain bacterial classes and phyla. Based on our
      findings, we propose a model that includes the involvement of multiple modules in
      the evolution of F1Fo ATP synthase. The central and peripheral stalk subunits
      provide a link for the integration of the F1/Fo modules.

PMID- 29177975
TI  - Hepatic safety analysis of trabectedin: results of a pharmacokinetic study with
      trabectedin in patients with hepatic impairment and experience from a phase 3
      clinical trial.
AB  - Purpose Trabectedin is metabolized by the liver and has been associated with
      transient, noncumulative transaminase elevation. Two recent studies further
      characterize hepatic tolerability with trabectedin therapy: a phase 1
      pharmacokinetic study (Study #1004; NCT01273493) in patients with advanced
      malignancies and hepatic impairment (HI), and a phase 3 study (Study #3007;
      NCT01343277) of trabectedin vs. dacarbazine in patients with advanced sarcomas
      and normal hepatic function. Methods In Study #1004, patients received a single 3
      h intravenous (IV) infusion of trabectedin: control group, trabectedin 1.3 mg/m2;
      HI group (baseline total bilirubin >1.5 and <=3* upper limit of normal [ULN]; AST
      and ALT <=2.5* ULN), trabectedin 0.58 or 0.9 mg/m2. In Study #3007, the
      trabectedin group received 1.5 mg/m2 by 24-h IV infusion every 3 weeks until
      disease progression or unacceptable toxicity. Results In Study #1004, dose
      normalized trabectedin exposure was higher in HI patients (n = 6) versus controls
      (n = 9) (geometric mean ratios [90% CI] AUClast: 1.97 [1.20; 3.22]). In Study
      #3007, following trabectedin administration, 90% of patients had elevated ALT
      (32% grade 3-4) and 84% had elevated AST (17% grade 3-4). Transaminase elevations
      were transient and noncumulative. Progression-free survival was similar in
      patients with grade 3-4 hepatotoxicity (n = 109) versus grade 0-2 hepatotoxicity
      (n = 231) (median [95% CI]: 4.63 [4.01, 5.85] months versus 3.55 [2.73, 4.63]
      months; P = 0.545, HR = 0.91 [0.68-1.23]). Conclusion Trabectedin treatment of
      patients with HI results in higher plasma exposures. Hepatotoxicity in patients
      with normal liver function can be effectively addressed through dose reductions
      and delays.

PMID- 29177976
TI  - Probability of misclassifying biological elements in surface waters.
AB  - Measurement uncertainties are inherent to assessment of biological indices of
      water bodies. The effect of these uncertainties on the probability of
      misclassification of ecological status is the subject of this paper. Four Monte
      Carlo (M-C) models were applied to simulate the occurrence of random errors in
      the measurements of metrics corresponding to four biological elements of surface
      waters: macrophytes, phytoplankton, phytobenthos, and benthic macroinvertebrates.
      Long series of error-prone measurement values of these metrics, generated by M-C
      models, were used to identify cases in which values of any of the four biological
      indices lay outside of the "true" water body class, i.e., outside the class
      assigned from the actual physical measurements. Fraction of such cases in the M-C
      generated series was used to estimate the probability of misclassification. The
      method is particularly useful for estimating the probability of misclassification
      of the ecological status of surface water bodies in the case of short sequences
      of measurements of biological indices. The results of the Monte-Carlo simulations
      show a relatively high sensitivity of this probability to measurement errors of
      the river macrophyte index (MIR) and high robustness to measurement errors of the
      benthic macroinvertebrate index (MMI). The proposed method of using Monte-Carlo
      models to estimate the probability of misclassification has significant potential
      for assessing the uncertainty of water body status reported to the EC by the EU
      member countries according to WFD. The method can be readily applied also in risk
      assessment of water management decisions before adopting the status dependent
      corrective actions.

PMID- 29177977
TI  - Muscle Oximetry in Sports Science: A Systematic Review.
AB  - BACKGROUND: Since the introduction (in 2006) of commercially available portable
      wireless muscle oximeters, the use of muscle near-infrared spectroscopy (NIRS)
      technology is gaining in popularity as an application to observe changes in
      muscle metabolism and muscle oxygenation during and after exercise or training
      interventions in both laboratory and applied sports settings. OBJECTIVES: The
      objectives of this systematic review were to highlight the application of muscle
      oximetry in evaluating oxidative skeletal muscle performance to sport activities
      and emphasize how this technology has been applied to exercise and training.
      METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines were followed in a systematic fashion to search, assess and synthesize
      existing literature on this topic. The Scopus and MEDLINE/PubMed electronic
      databases were searched to 1 March 2017. Potential inclusions were screened
      against eligibility criteria relating to recreationally trained to elite
      athletes, with or without training programs, who must have assessed physiological
      variables monitored by commercial oximeters or NIRS instrumentation. RESULTS: Of
      the 14,609 identified records, only 57 studies met the eligibility criteria. This
      systematic review highlighted a number of key findings in 16 sporting activities.
      Overall, NIRS information can be used as a marker of skeletal muscle oxidative
      capacity and for analyzing muscle performance factors. CONCLUSIONS: Although NIRS
      instrumentation is promising in evaluating oxidative skeletal muscle performance
      when used in sport settings, there is still the need for further instrumental
      development and randomized/longitudinal trials to support the detailed advantages
      of muscle oximetry utilization in sports science.

PMID- 29177979
TI  - Photobiomodulation effect on children's scars.
AB  - The management of burn scars has become one of the major clinical challenges in
      the developing countries which involve enormous treatment cost; this needs new
      methods for better cost benefit relationship. The objective of the study is to
      analyze the effectiveness of low-level laser therapy on post-burn scar tissue in
      children. A randomized controlled study included 15 children, ranging from 2 to
      10 years of age, presenting with burn scars. They received diode laser and
      topical treatment. Each scar was divided into two halves. One half was treated
      with laser therapy and topical treatment (study area), and the other half was
      treated with topical treatment only (control area). The children were evaluated
      before and after 3 months of the study by Vancouver Scar Scale (VSS),
      ultrasonography (U/S), and laser Doppler perfusion imaging. Significant
      improvement was reported in the studied area compared to the control area for
      patients with P values (P = 0.005) and (P = 0.0001) for VSS and U/S scores,
      respectively. No difference was detected for blood perfusion to the scar between
      both areas (P = 0.18). In addition, no adverse effect was reported.
      Photobiomodulation is an efficient and safe therapeutic modality for post-burn
      hypertrophic scars in children and should be considered a part of combination
      therapy for better results.

PMID- 29177978
TI  - Zinc deficiency as a mediator of toxic effects of alcohol abuse.
AB  - OBJECTIVE: To review data on the role of ethanol-induced alteration of Zn
      homeostasis in mediation of adverse effects of alcohol abuse. METHODS: The
      scholarly published articles on the association between Zn metabolism and alcohol
      associated disorders (liver, brain, lung, gut dysfunction, and fetal alcohol
      syndrome) have been reviewed. RESULTS: It is demonstrated that alcohol-induced
      modulation of zinc transporters results in decreased Zn levels in lungs, liver,
      gut, and brain. Zn deficiency in the gut results in increased gut permeability,
      ultimately leading to endotoxemia and systemic inflammation. Similarly, Zn
      deficiency in lung epithelia and alveolar macrophages decreases lung barrier
      function resulting in respiratory distress syndrome. In turn, increased
      endotoxemia significantly contributes to proinflammatory state in alcoholic liver
      disease. Finally, impaired gut and liver functions may play a significant role in
      alcoholic brain damage, being associated with both increased proinflammatory
      signaling and accumulation of neurotoxic metabolites. It is also hypothesized
      that ethanol-induced Zn deficiency may interfere with neurotransmission. Similar
      changes may take place in the fetus as a result of impaired placental zinc
      transfer, maternal zinc deficiency, or maternal Zn sequestration, resulting in
      fetal alcoholic syndrome. Therefore, alcoholic Zn deficiency not only mediates
      the adverse effects of ethanol exposure, but also provides an additional link
      between different alcohol-induced disorders. CONCLUSIONS: Generally, current
      findings suggest that assessment of Zn status could be used as a diagnostic
      marker of metabolic disturbances in alcohol abuse, whereas modulation of Zn
      metabolism may be a potential tool in the treatment of alcohol-associated
      disorders.

PMID- 29177980
TI  - Cardiac autonomic responses and number of repetitions maximum after LED
      irradiation in the ipsilateral and contralateral lower limb.
AB  - The aim of this study was to verify the maximum number of repetitions, fatigue
      index, blood lactate concentration ([Lac]), and cardiac autonomic responses after
      LED irradiation (LEDI) in the ipsilateral and contralateral limb. Twelve male
      subjects (22.0 +/- 3.86 years; weight 82.94 +/- 12.58 kg; height 1.77 +/- 0.05
      m), physically active, took part in this study. The subjects underwent a one
      repetition maximum (1RM) test and performed four randomly experimental sessions
      in the horizontal leg press exercise, which consisted in four sets of maximum
      repetitions at 80% of 1RM. The subjects performed two experimental sessions
      applying LED active or placebo on ipsilateral limb and two experimental sessions
      applying LED active or placebo on contralateral limb prior exercise and in the
      interval of sets on quadriceps and hamstrings muscles. A number of repetitions
      and fatigue index were verified. [Lac] and heart rate variability (HRV) were
      collected during post-exercise recovery and analyzed. It was observed that active
      LEDI promoted an increase in maximal number of repetitions (LEDI = 44.4 +/- 9.0
      vs placebo = 39.9 +/- 11.4; p < 0.05) and decreases the fatigue index (LEDI =
      34.3 +/- 21.8% vs placebo = 50.0 +/- 26.6%; p < 0.05) comparing to placebo
      situation, only in the ipsilateral application. There were no differences on
      [Lac] and in HRV parameters comparing LEDI vs placebo on post-exercise recovery
      in both applications (p > 0.05). The LEDI improves performance only in the
      ipsilateral application, but there were no differences on [Lac] and cardiac
      autonomic responses after exercise for both the applications.

PMID- 29177981
TI  - Long-term incidence of inappropriate shocks in patients with implantable
      cardioverter defibrillators in clinical practice-an underestimated complication?
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICD) are life-saving device
      therapy, and patients often carry devices for decades with interim pulse
      generator exchanges. Inappropriate shocks are associated with impaired quality of
      life and increased mortality, but available data on their incidence and etiology
      outside of clinical trials is limited and usually restricted to the lifespan of a
      singular device. We hypothesized that the incidence in clinical practice is
      underestimated and aimed this study to retrospectively assess the long-term
      incidence and etiology of inappropriate shocks in a real-world cohort of patients
      with multiple ICDs over a long follow-up period. METHODS: Patients with ICDs
      implanted between 1998 and 2012 in two Swiss cardiology departments and at least
      one device exchange in the same department thereafter were included in this
      cohort. Retrospective analysis with follow-up until 2016 was conducted to assess
      incidence and etiology of inappropriate ICD shocks. RESULTS: Two hundred forty
      nine ICDs were implanted in 100 patients (mean age: 60.1 +/- 11.7; 80% male).
      Over a mean follow-up time of 11.2 (+/- 3.6) years, 555 shocks occurred in 55
      patients. One hundred twenty-three (22%) shocks in 23 (23%) patients were
      inappropriate. Supraventricular arrhythmia and oversensing were the most frequent
      causes of inappropriate shock. Patients with younger age or previous
      supraventricular arrhythmias were at increased risk of inappropriate shocks.
      Patients with inappropriate shocks during the lifespan of their first ICD were at
      increased risk for inappropriate shocks in subsequent devices. CONCLUSIONS:
      Inappropriate shocks are an underestimated and frequent problem in clinical
      practice with an incidence that may exceed numbers of previously reported
      clinical trials with shorter follow-up periods. Patients at increased risk for
      inappropriate shocks need careful evaluation of potential therapeutic
      optimization strategies including pharmacological treatment, device programming,
      electrophysiological ablation, device downgrading, and telemonitoring.

PMID- 29177983
TI  - Ask the rheumatologist online: a qualitative analysis of a web-based service.
AB  - The objective of this study was to analyze the use of an Ask-the-Rheumatologist
      website service. All questions submitted were analyzed for gender, geographic
      location, topic area, disease, appropriateness, personal experience, and whether
      the answer is found elsewhere on the hosting website. The number of total visits
      and their geographic location was determined. The web service was visited 7985
      times. Two hundred twenty-seven questions were submitted, with a majority related
      to personal experience and inflammatory rheumatic disease. One hundred six
      questions did not have answers available elsewhere on the website. Seventy
      questions were deemed inappropriate. Ask-the-Rheumatologist was visited
      frequently, demonstrating an innovative method of knowledge-transfer between
      health professionals, patients, and the general public.

PMID- 29177982
TI  - Two in one is better than one plus one: comparison of adverse events between
      combining electrophysiological examination and coronary angiography versus
      performing them consecutively.
AB  - PURPOSE: In some patients, both an electrophysiological examination (EPS) and a
      coronary angiography (CA) are necessary. It might be preferable to choose a
      combined approach of EPS and CA versus performing them consecutively. The purpose
      of this study is to evaluate the type and rate of adverse events between both
      approaches. METHODS: Patients were eligible if they underwent a CA and an EPS in
      a combined approach or in a time interval of at most 2 months. In all patients,
      clinical adverse events were recorded. RESULTS: A total of 1184 patients were
      included. CA and EPS were performed in a combined procedure (comb) in 492
      patients, whereas they were performed consecutively in 692 patients (cons). The
      acute major complication rate was 0.67%, showing no differences between both
      groups. In the comb 6.9% and in the cons 6.6% of vascular complications were
      observed (p = 0.20). The rates of AV fistula and hematoma needing transfusion
      showed a significantly higher rate in the cons group (p = 0.018 and p = 0.045,
      respectively). In a multivariate logistic regression analysis, age was a
      significant predictor for groin complications. After propensity matching, AV
      fistula occurred significantly more often in the cons group (p = 0.002).
      CONCLUSION: Overall, serious adverse events were rare and there were no
      differences between the combined approach of EPS and CA and the consecutive
      approach; however, the occurrence of AV fistula and groin hematoma needing
      transfusion occurred significantly less in the combined procedure group.
      Therefore, a combined approach is preferable to a consecutive one.

PMID- 29177984
TI  - Clinical characteristics of conduction disturbance in patients with Behcet's
      disease.
AB  - To summarized clinical features of Behcet's patients with conduction disturbances
      and explore the underlying risk factors. A retrospective case-control study was
      conducted in Anzhen Hospital, Capital Medical University. Demographic data,
      clinical features, laboratory results, treatments, and fatality rate during
      hospital stay were analyzed. We found 23.1% of Behcet's disease had conduction
      disturbances and 84.0% had aortic valvular insufficiency. The male percentage of
      the Behcet's disease patients with conduction disturbances was significantly
      higher than controls (88.9 vs. 61.7%, P = 0.03). The echocardiography showed left
      ventricular end-diastolic diameter [64.00 (18) vs. 48.00 (15) mm, P = 0.000];
      left ventricular end-contraction diameter [47.50 (11) vs. 30 (13) mm, P = 0.000];
      left atrial diameter [47 (17) vs. 34 (14) mm, P = 0.001]; and left ventricular
      ejection fraction [60 (10) vs. 63 (13) mm, P = 0.023] were significantly
      different between two groups. Aortic valvular insufficiency was an independent
      risk factor for Behcet's disease with conduction disturbances (OR = 17.830; 95%
      CI 2.106, 150.981; P = 0.008). Conduction disturbance in Behcet's disease
      deserved attention. The diagnosis of BD and evaluation of conduction disturbance
      should be kept in mind when accepting patients with valvular regurgitation.

PMID- 29177985
TI  - Erratum to: Oxygen Transport to Tissue XXXIV.

PMID- 29177986
TI  - Metallurgy of soft spheres with hard core: From BCC to Frank-Kasper phases.
AB  - Understanding how soft particles can fill the space is still an open question.
      Structures far from classical FCC or BCC phases are now commonly experimentally
      observed in many different systems. Models based on pair interaction between soft
      particles are at present much studied in 2D. Pair interactions with two different
      lengths have been shown to lead to quasicrystalline architectures. It is also the
      case for a hard core with a square repulsive shoulder potential. In 3D, global
      approaches have been proposed for instance by minimizing the interface area
      between the deformed objects in the case of foams or micellar systems or using a
      self-consistent mean-field theory in copolymer melts. In this paper we propose to
      compare a strong van der Waals attraction between spherical hard cores and an
      elastic energy associated to the deformation of the soft corona. This deformation
      is measured as the shift between the deformed shell compared to a corona with a
      perfect spherical symmetry. The two main parameters in this model are: the hard
      core volume fraction and the weight of the elastic energy compared to the van der
      Waals one. The elastic energy clearly favours the BCC structure but large van der
      Waals forces favor Frank and Kasper phases. This result opens a route towards
      controlling the building of nanoparticle superlattices with complex structures
      and thus original physical properties.

PMID- 29177987
TI  - A case of an elderly man who required repeated repair of a ventricular septal
      defect and tricuspid rupture after blunt chest trauma.
AB  - Several cases of traumatic ventricular septal defect (VSD) have been reported.
      However, traumatic VSD complicated by tricuspid rupture is rare. We report a case
      of traumatic VSD with tricuspid rupture who required repeated repair of both
      conditions. A 69-year-old man was transferred to our hospital for emergent
      surgical repair of traumatic VSD and tricuspid rupture. Although emergent repair
      was performed, a new left-to-right shunt and moderate tricuspid regurgitation
      appeared during his postoperative course. A reoperation was performed 4 months
      after the first operation. The borders of the defect were very fibrotic and
      strong compared with those in the first operation. Surgical treatment of
      traumatic VSD should be postponed in hemodynamically stable patients. When
      emergent repair is performed, careful follow-up is necessary to diagnose new VSD.

PMID- 29177988
TI  - Early Life Characteristics and Neurodevelopmental Phenotypes in the Mount Sinai
      Children's Environmental Health Center.
AB  - Neurodevelopmental outcomes including behavior, executive functioning, and IQ
      exhibit complex correlational structures, although they are often treated as
      independent in etiologic studies. We performed a principal components analysis of
      the behavioral assessment system for children, the behavior rating inventory of
      executive functioning, and the Wechsler scales of intelligence in a prospective
      birth cohort, and estimated associations with early life characteristics. We
      identified seven factors: (1) impulsivity and externalizing, (2) executive
      functioning, (3) internalizing, (4) perceptual reasoning, (5) adaptability, (6)
      processing speed, and (7) verbal intelligence. Prenatal fish consumption,
      maternal education, preterm birth, and the home environment were important
      predictors of various neurodevelopmental factors. Although maternal smoking was
      associated with more adverse externalizing, executive functioning, and adaptive
      composite scores in our sample, of the orthogonally-rotated factors, smoking was
      only associated with the impulsivity and externalizing factor ([Formula: see
      text] - 0.82, 95% CI - 1.42, - 0.23). These differences may be due to
      correlations among outcomes that were accounted for by using a phenotypic
      approach. Dimension reduction may improve upon traditional approaches by
      accounting for correlations among neurodevelopmental traits.

PMID- 29177989
TI  - Consumption of caffeinated beverages and serum concentrations of sex steroid
      hormones in US men.
AB  - BACKGROUND: By modulating the levels of sex steroid hormones and sex hormone
      binding globulin (SHBG), caffeine could be a factor in the development of several
      conditions in men, including prostate cancer. The aim of this study was to
      evaluate if caffeine consumption is associated with concentrations of sex steroid
      hormones and SHBG in men. METHODS: 1,410 men aged 20 + years who attended the
      morning examination session of the Third National Health and Nutrition
      Examination Survey (1988-1991) were included in the analysis. Coffee and soft
      drink consumption was assessed using a food frequency questionnaire. Daily
      caffeine intake was estimated by multiplying caffeine content per cup times the
      daily frequency of coffee, tea, or soft drink consumption. Serum levels of
      hormones and SHBG were measured by immunoassay. Associations of frequency of
      beverage consumption or estimated caffeine intake with hormone levels were
      examined using multivariable linear regression. RESULTS: Coffee consumption was
      positively associated with SHBG concentration (p = 0.045) taking lifestyle
      factors into account, but mutually adjusting for testosterone and estradiol
      attenuated the association; no association with SHBG was observed for soft drink
      consumption or caffeine intake. No associations between caffeinated beverage
      consumption and androgen or estrogen concentrations were observed. CONCLUSION:
      Men who drink coffee more frequently may have higher circulating SHBG
      concentration, but there were no consistent associations for soft drinks or
      caffeine intake.

PMID- 29177990
TI  - Atomoxetine-induced hyperadrenergic postural tachycardia syndrome: a case report.

PMID- 29177991
TI  - Correction to: Treatment with the PPARgamma Agonist Pioglitazone in the Early
      Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis
      Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.
AB  - In the original publication of the article, the second author (Keiko T. Kitazato)
      was missing.

PMID- 29177992
TI  - Effect of Acrocomia aculeata Kernel Oil on Adiposity in Type 2 Diabetic Rats.
AB  - The macauba palm (Acrocomia aculeata) is native of tropical America and is found
      mostly in the Cerrados and Pantanal biomes. The fruits provide an oily pulp, rich
      in long chain fatty acids, and a kernel that encompass more than 50% of lipids
      rich in medium chain fatty acids (MCFA). Based on biochemical and nutritional
      evidences MCFA is readily catabolized and can reduce body fat accumulation. In
      this study, an animal model was employed to evaluate the effect of Acrocomia
      aculeata kernel oil (AKO) on the blood glucose level and the fatty acid deposit
      in the epididymal adipose tissue. The A. aculeata kernel oil obtained by cold
      pressing presented suitable quality as edible oil. Its fatty acid profile
      indicates high concentration of MCFA, mainly lauric, capric and caprilic. Type 2
      diabetic rats fed with that kernel oil showed reduction of blood glucose level in
      comparison with the diabetic control group. Acrocomia aculeata kernel oil showed
      hypoglycemic effect. A small fraction of total dietary medium chain fatty acid
      was accumulated in the epididymal adipose tissue of rats fed with AKO at both low
      and high doses and caprilic acid did not deposit at all.

PMID- 29177993
TI  - Classification of hospital admissions into emergency and elective care: a machine
      learning approach.
AB  - Rising admissions from emergency departments (EDs) to hospitals are a primary
      concern for many healthcare systems. The issue of how to differentiate urgent
      admissions from non-urgent or even elective admissions is crucial. We aim to
      develop a model for classifying inpatient admissions based on a patient's primary
      diagnosis as either emergency care or elective care and predicting urgency as a
      numerical value. We use supervised machine learning techniques and train the
      model with physician-expert judgments. Our model is accurate (96%) and has a high
      area under the ROC curve (>.99). We provide the first comprehensive
      classification and urgency categorization for inpatient emergency and elective
      care. This model assigns urgency values to every relevant diagnosis in the ICD
      catalog, and these values are easily applicable to existing hospital data. Our
      findings may provide a basis for policy makers to create incentives for hospitals
      to reduce the number of inappropriate ED admissions.

PMID- 29177994
TI  - Are shocks to renewable energy consumption permanent or temporary? Evidence from
      54 developing and developed countries.
AB  - The renewable energy sources are considered as the important factor to decrease
      the level of carbon emissions and to promote the global green economy.
      Understanding the dynamics of renewable energy consumption, this paper analyzes
      whether there is a unit root in renewable energy consumption in 54 countries over
      the period 1971-2016. To this end, the unit root test of Narayan-Popp with two
      endogenous (unknown) breaks is implemented. The paper finds that renewable energy
      consumption series are stationary around a level and the time trend in 45 of 54
      countries. In other words, renewable energy consumption follows a unit root
      process only in nine countries: Brazil, China, Colombia, India, Israel, Japan,
      the Netherlands, Spain, and Turkey. The evidence implies that renewable energy
      demand policies, which aimed to decrease the carbon emissions, will only have
      permanent effects in those nine countries.

PMID- 29177995
TI  - Photocatalytic decomposition of N2O over g-C3N4/WO3 photocatalysts.
AB  - Although the nitrous oxide belongs among three of the most contributing
      greenhouse gases to global warming, it is quite neglected by photocatalytic
      society. The g-C3N4 and WO3 composites were therefore tested for the
      photocatalytic decomposition of N2O for the first time. The pure photocatalysts
      were prepared by simple calcination of precursors, and the composites were
      prepared by mixing of suspension of pure components in water followed by
      calcination. The structural (X-ray diffraction, X-ray photoelectron spectroscopy,
      high-resolution transmission electron microscopy), textural (N2 physisorption),
      and optical properties (diffuse reflectance spectroscopy, photoluminescence
      spectroscopy, photoelectrochemical measurements) of all composites were
      correlated with photocatalytic activity. The experimental results and results
      from characterization techniques confirmed creation of Z-scheme in the WO3/g-C3N4
      composites, which was confirmed by hydroxyl radicals' trapping measurements. The
      photocatalytic decomposition of N2O was carried out in the presence of UVA light
      (peak intensity at 365 nm) and the 1:2 WO3/g-C3N4 composite was the most active
      one, but the photocatalytic activity was just negligibly higher than that of pure
      WO3. This is caused by relatively weak interaction between WO3 and g-C3N4 which
      was revealed from XPS.

PMID- 29177996
TI  - Heavy-metal speciation redistribution in solid phase and potential environmental
      risk assessment during the conversion of MSW incineration fly ash into molten
      slag.
AB  - The alkalinity (AKash), BCR sequential extraction method, and principle component
      analysis (PCA) were adopted to investigate the heavy-metal partitioning and their
      speciation redistribution in solid phase in ash-melting process. The results
      indicated that the conversion of Zn-OXI (oxidisable fraction) into Zn-RES
      (residual fraction) and the decomposition of Cu-OXI fraction were prevailing in
      solid-phase reaction. Moreover, the alkalinity reduction from AKash = 2.0 to
      AKash = 1.2 had positive implications for the concentration reduction of As-RED
      (reducible fraction), Zn-RED, and Pb-RES fractions in slags. The modified
      synthesis toxicity index (STIM) calculation model was introduced to investigate
      the potential ecological risk (PEI) of heavy metals in the recycling and
      utilization of molten slag. Based on STIM calculation model, PEI of heavy metal
      in hazardous materials was classified into five ranks, such as serious pollution
      (STIM > 462), heavy pollution (330 < STIM < 462), moderate pollution (132 < STIM
      < 330), mild pollution (0 < STIM < 132), and no pollution (STIM = 0). The molten
      slags produced from fly ash can be directly reused as building materials like
      freestone and ceramics due to the mild PEI.

PMID- 29177997
TI  - Study on diesel vertical migration characteristics and mechanism in water-bearing
      sand stratum using an automated resistivity monitoring system.
AB  - Oil spills frequently occur on both land and sea. Petroleum in mobile phase will
      cause serious pollution in the sediment and can form a secondary pollution
      source. Therefore, it is very important to study the migration of petroleum in
      sediments ideally in a rapid and simplified approach. The release of diesel was
      simulated using fine beach sand to construct a model aquifer, and dynamic
      monitoring was carried out using an automated monitoring system including a
      resistivity probe originally developed by our research group. The mobile phase
      migration fronts were determined accurately using wavelet analysis method
      combined with resistivity curve method. Then, a relationship between resistivity
      and the joint oil-water content was established. The main conclusions were as
      follows. The seepage velocity of the diesel with high mobility at the initial
      stage of infiltration was faster, followed by a period when gravity seepage was
      dominant, and finally a redistribution period at the later stage, which was
      mainly an oil-water displacement process. The resistivity trends for diesel
      infiltration in different water-saturated soil layers varied with depth. The
      resistivity in the vadose zone fluctuated significantly, increasing initially and
      later decreasing. The resistivity change in the capillary zone was relatively
      small and constant in the initial stage; then, it increased and subsequently
      decreased. The resistivity in the saturated zone was basically unchanged with
      depth, and the value became slightly larger than the background value over time.
      Overall, for a large volume of mobile phase diesel leakage, the arrival migration
      fronts can be detected by wavelet analysis combined with resistivity curves. The
      thickness of the oil slick in the capillary zone can be estimated by resistivity
      changes. The relationships between resistivity and both the moisture content and
      oil-water joint saturation are in agreement with the linear models. The research
      results provide basic data and a new data processing method for monitoring of
      contaminated sites following major oil spills using the resistivity method.

PMID- 29177999
TI  - Evaluation of sources and fate of nitrates in the western Po plain groundwater
      (Italy) using nitrogen and boron isotopes.
AB  - Diffuse nitrate pollution in groundwater is currently considered one of the major
      causes of water quality degradation. Determining the sources of nitrate
      contamination is an important first step for a better management of water
      quality. Thus, the isotopic composition of nitrate (delta15NNO3 and delta18ONO3)
      and boron (delta11B) were used to evaluate nitrate contamination sources and to
      identify geochemical processes occurring in the shallow and deep aquifers of the
      Turin-Cuneo plain (NW Italy). The study area is essentially an agricultural zone,
      where use of synthetic nitrogenous fertilizers and organic manure is a common
      practice and the connection to sewer services is locally lacking. Also livestock
      farming are highly developed. A groundwater sampling campaign was performed on 34
      wells in the shallow aquifer and 8 wells in the deep aquifers, to analyze
      nitrate, chloride, boron, delta15NNO3, delta18ONO3 and delta11B. Isotope data of
      nitrate indicate that nitrate contamination in the Turin-Cuneo plain originates
      from mixtures of synthetic and organic sources, slightly affected by
      denitrification, and manure or septic tank effluents. Moreover, boron isotopes
      were used to discriminate further among the main anthropogenic sources of
      pollution. The analyses results confirm that both animal manure and domestic
      sewage, especially under the city of Turin, can contribute to the nitrate
      contamination. The isotope analysis was also used for the evaluation of
      denitrification and nitrification processes: contrary to expectations, a
      significant denitrification phenomenon was assessed only in the shallow
      unconfined aquifer, especially in the Poirino Plateau, the most contaminated
      sector of the study area.

PMID- 29177998
TI  - Fast trace determination of nine odorant and estrogenic chloro- and bromo
      phenolic compounds in real water samples through automated solid-phase extraction
      coupled with liquid chromatography tandem mass spectrometry.
AB  - A fast and reliable method was developed for simultaneous trace determination of
      nine odorous and estrogenic chloro- and bromo-phenolic compounds (CPs and BPs) in
      water samples using solid-phase extraction (SPE) coupled with liquid
      chromatography tandem mass spectrometry (LC-MS/MS). For sample preparation, the
      extraction efficiencies of two widely applied cartridges Oasis HLB and Sep-Pak
      C18 were compared, and the Oasis HLB cartridge showed much better extraction
      performance; pH of water sample also plays important role on extraction, and pH =
      2-3 was found to be most appropriate. For separation of the target compounds,
      small addition of ammonium hydroxide can obviously improve the detection
      sensitivity, and the optimized addition concentration was determined as 0.2%. The
      developed efficient method was validated and showed excellent linearity (R 2 >
      0.995), low limit of detection (LOD, 1.9-6.2 ng/L), and good recovery
      efficiencies of 57-95% in surface and tap water with low relative standard
      deviation (RSD, 1.3-17.4%). The developed method was finally applied to one tap
      and one surface water samples and most of these nine targets were detected, but
      all of them were below their odor thresholds, and their estrogen equivalent (EEQ)
      were also very low.

PMID- 29178000
TI  - A procedure to evaluate the factors determining the elemental composition of
      PM2.5. Case study: the Veneto region (northeastern Italy).
AB  - The Po Valley is one of the most important hot spots in Europe for air pollution.
      Morphological features and anthropogenic pressures lead to frequent breaching of
      air quality standards and to high-pollution episodes in an ~46 * 103-km2-wide
      alluvial lowland. Therefore, it is increasingly important to study the air
      quality in a wide geographical scale to better implement possible and successful
      mitigation measures. The Veneto region lies in the eastern part of the Po Valley
      and the elemental composition of PM has been mainly studied in the Venice area,
      whereas scarce data are available for the remaining territory of the region. In
      this study, the elemental composition of PM2.5 was investigated over 1 year (2012
      2013) at six major cities of the Veneto region. Samples were analyzed for 16
      elements (Ca, Al, Fe, S, K, Mg, Ti, Mn, Zn, Ba, As, Ni, Pb, Sb, V, and Cu), and
      results were processed to investigate spatial and seasonal variations, the
      influence of meteorological factors, and the most probable sources by using a
      procedure based on (i) elemental ratios (Cu/Sb, Cu/Zn, Cu/Pb, Mn/V, V/Ni, and
      Zn/Pb), (ii) cluster analysis on wind data, and (iii) conditional probability
      function (CPF). The percentage of elements in PM2.5 ranged between 11 and 20%,
      and Ca and S were the most abundant elements in the region. Typical seasonal
      variations and similar trends were exhibited by each element, especially in the
      lowland. Some elements such as Zn, K, Mn, Pb, and Sb were found at high
      concentrations during the cold period. However, no similar dispersion processes
      were observed throughout the region, and their concentrations were mostly
      depending on individual local sources. In the alpine and foothill parts of the
      region, lower concentrations were recorded with respect to the Po Valley cities,
      which resulted enriched of most of the elements considered in this study. The
      cluster analysis on wind data and the CPF of the ratio-related sources
      demonstrated that a widespread pollution condition exists in the region, apart
      from the coastal area. However, specific directions (e.g., a link with high
      traffic roads, industrial areas, and airports) resulted the most probable
      explanation for each ratio-related source. In addition, the Veneto region hosts
      one of the most important Mediterranean ports for the cruise sector (Venice
      harbor), and its impact was previously demonstrated in the historical city
      center. In this study, the impact of Venice shipping emissions was estimated to
      be 3.5% of PM2.5 in some particular days.

PMID- 29178001
TI  - Volatile organic compounds and nitric oxide as responses of a Brazilian tropical
      species to ozone: the emission profile of young and mature leaves.
AB  - The emission profile of volatile organic compounds (VOCs) and nitric oxide (NO)
      in young and mature leaves of Croton floribundus was assessed in plants exposed
      to filtered air (FA) and ozone-enriched filtered air (FA+O3). After the period of
      exposure, leaves were enclosed in polyethylene terephthalate bags and VOCs were
      collected in young and mature leaves. Both young and mature leaves constitutively
      emitted the same VOC, but the concentrations were higher in young leaves. O3
      exposure induced the emission of sesquiterpenes (mainly beta-caryophyllene) known
      as antioxidant compounds that may scavenge O3. Young leaves were the highest
      emitters of sesquiterpenes. O3 induced a rapid accumulation of NO in different
      tissues and leaf developmental stages; this accumulation was marked in palisade
      and spongy parenchyma cells in young and mature leaves, respectively. O3 altered
      the levels of the signaling compound methyl salicylate (MeSA). Moreover, our data
      showed that NO together with VOC emissions, such as geranyl acetate, alpha
      cadiene, trans-farnesol, cis-beta-farnesene, and MeSA, participate of plant
      defense mechanisms against the oxidative damage caused by O3.

PMID- 29178002
TI  - Dysregulatory effects of retinoic acid isomers in late zebrafish embryos.
AB  - All-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) are two natural
      derivatives of vitamin A that contribute to the normal vertebrate development by
      affecting gene expression through the retinoic acid signalling pathway. We show
      transcriptomic effects of the ectopic addition of atRA or 9cRA to zebrafish
      embryos at the posthatching embryonic stage. Exposure for 24 or 72 h to sublethal
      concentrations of both isomers resulted in characteristic transcriptome changes,
      in which many proliferation and development-related genes became underexpressed,
      whereas genes related to retinoid metabolism and some metabolic functions became
      overrepresented. While short and long exposures elicit essentially the same set
      of genes, atRA specifically induced expression of a specific subset of proteases,
      likely acting at the extracellular level, and of elements of the response to
      xenobiotics. These results reflect the well-known antiproliferative activity of
      retinoids, and they suggest a dysregulation of the developmental process at final
      stages of embryogenesis. They also indicate a potential role of endopeptidases as
      markers of developmental alterations, as well as their possible control by the
      retinoic signalling pathway. We propose to monitor mRNA levels of cyp16a, cyp16b,
      and cyp16c in zebrafish embryos as a bioassay for retinoid disruption.

PMID- 29178004
TI  - PCDD/PCDF formation in the chlor-alkali process-laboratory study and comparison
      with patterns from contaminated sites.
AB  - Studies on the formation of polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs) during the electrolysis of sodium chloride
      solution (brine) using graphite or titanium electrodes were carried out at a
      laboratory scale. High concentrations of PCDFs but no PCDDs were formed in tests
      using graphite electrodes. With titanium electrodes, PCDFs were only formed when
      tar pitch was added and mainly originated from the dibenzofuran present in the
      tar. For the first time, a detailed assessment of the formation of mono- to
      octachlorinated PCDD/PCDF from tar pitch was investigated. The assessment
      included of the chlorination steps proved that PCDFs were formed by successive
      lateral chlorinated from dibenzofuran to MonoCDFs, DiCDFs, and TriCDFs to form
      the typical known "chlorine pattern" of TetraCDF to OctaCDF with a dominance of
      1,2,7,8- and 2,3,7,8-TetraCDFs, 1,2,3,7,8-PentaCDF, and 1,2,3,4,7,8-HexaCDF as
      marker congeners. The final homologue distributions depended on reaction time and
      reaction temperature. In addition, electrolysis with non-chlorinated dibenzo-p
      dioxins, dibenzofuran, and biphenyl was carried out. As a result, PCDDs, PCDFs,
      and PCB were formed at comparable yields. Congener patterns in soil samples from
      a PCDD/F-contaminated site where chlor-alkali electrolysis had been operated for
      decades in Japan had identical isomer distribution demonstrating the source and
      contamination potential and risk of these processes. Therefore, sites where in
      the past 120 years chlor-alkali electrolysis has been operated or where residues
      from chlor-alkali production or other chlorine using industries have been
      disposed should be assessed for their pollution level and exposure relevance. The
      assessment of total organohalogen content revealed that PCDF is only a small
      fraction of organohalogens in the contaminated soils. For an appropriate risk
      assessment, also other chlorinated aromatic compounds such as PCBs or PCNs need
      to be considered.

PMID- 29178003
TI  - Enhanced phosphorus removal using acid-treated magnesium slag particles.
AB  - Magnesium-enriched magnesium slag particles (MSPs) can be used as an adsorption
      substrate as well as the magnesium source for struvite precipitation. In this
      study, an HCl treatment was used to enhance MSPs for phosphorus removal. After
      soaking in 1 mol/L HCl, an 11.27% decrease in median diameter (D50) and a 6.73%
      increase in specific surface area were observed when compared with the original
      MSPs. The improvement of the MSP surface properties resulted in 188.96 mg/kg
      increase in the PO43- adsorption capacity. Irrespective of HCl treatment, the
      phosphorus adsorption process followed the Dubinin-Radushkevich (D-R) model much
      more accurately than the Langmuir and Freundlich equations with correlation
      coefficients higher than 0.94. The adsorption free energy obtained through the D
      R model revealed a 9.75% decrease after HCl treatment. Sequential fraction
      extraction results indicated that 96% of the Mg2+ released from the HCl-treated
      MSPs came from acid-soluble magnesium (exchangeable and carbonate-bound). Mg2+
      obtained from HCl-treated solutions provided a reliable magnesium source for
      struvite precipitation. The PO43- removal rate can reach 53.63% with the optimal
      pH value of 10.0 and molar ratio of NH4+ to PO43- of 1:1. Struvite precipitation
      and adsorption can simultaneously occur in HCl-treated MSP solution. It
      contributed 63.19% to the overall PO43- removal and is a major contributor
      compared with adsorption. Thus, HCl treatment greatly enhanced the potential of
      MSPs for phosphorus removal due to an improved adsorption capacity and is a
      reliable Mg2+ source for struvite precipitation.

PMID- 29178005
TI  - Effect of single and repeated heat stress on chemical signals of heat shock
      response cascade in the rat's heart.
AB  - Exposure to sublethal heat stress activates a complex cascade of signaling
      events, such as activators (NO), signal molecules (PKCepsilon), and mediators
      (HSP70 and COX-2), leading to implementation of heat preconditioning, an adaptive
      mechanism which makes the organism more tolerant to additional stress. We
      investigated the time frame in which these chemical signals are triggered after
      heat stress (41 +/- 0.5 degrees S/45 min), single or repeated (24 or 72 h after
      the first one) in heart tissue of male Wistar rats. The animals were allowed to
      recover 24, 48 or 72 h at room temperature. Single heat stress caused a
      significant increase of the concentration of HSP70, NO, and PKC level and
      decrease of COX-2 level 24 h after the heat stress, which in the next course of
      recovery gradually normalized. The second heat stress, 24 h after the first one,
      caused a significant reduction of the HSP70 levels, concentration of NO and PKCE,
      and significant increase of COX-2 concentration. The second exposure, 72 h after
      the first heat stress, caused more expressive changes of HSP70 and NO in the 24 h
      recovery groups. The level of PKCE was not significantly changed, but there was
      significantly increased COX-2 concentration during recovery. Serum activity of
      AST, ALT, and CK was reduced after single exposure and increased after repeated
      exposure to heat stress, in both time intervals. In conclusion, a longer period
      of recovery (72 h) between two consecutive sessions of heat stress is necessary
      to achieve more expressive changes in mediators (HSP70) and triggers (NO) of heat
      preconditioning.

PMID- 29178006
TI  - Diagnostic accuracy of coronary opacification derived from coronary computed
      tomography angiography to detect ischemia: first validation versus single-photon
      emission computed tomography.

PMID- 29178008
TI  - Trace-metal contamination in the glacierized Rio Santa watershed, Peru.
AB  - The objective of this research is to characterize the variability of trace metals
      in the Rio Santa watershed based on synoptic sampling applied at a large scale.
      To that end, we propose a combination of methods based on the collection of
      water, suspended sediments, and riverbed sediments at different points of the
      watershed within a very limited period. Forty points within the Rio Santa
      watershed were sampled between June 21 and July 8, 2013. Forty water samples, 36
      suspended sediments, and 34 riverbed sediments were analyzed for seven trace
      metals. The results, which were normalized using the USEPA guideline for water
      and sediments, show that the Rio Santa water exhibits Mn concentrations higher
      than the guideline at more than 50% of the sampling points. As is the second
      highest contaminating element in the water, with approximately 10% of the samples
      containing concentrations above the guideline. Sediments collected in the Rio
      Santa riverbed were heavily contaminated by at least four of the tested elements
      at nearly 85% of the sample points, with As presenting the highest normalized
      concentration, at more than ten times the guideline. As, Cd, Fe, Pb, and Zn
      present similar concentration trends in the sediment all along the Rio Santa.The
      findings indicate that care should be taken in using the Rio Santa water and
      sediments for purposes that could affect the health of humans or the ecosystem.
      The situation is worse in some tributaries in the southern part of the watershed
      that host both active and abandoned mines and ore-processing plants.

PMID- 29178007
TI  - Correction to: Pharmacokinetics of Fentanyl and Its Derivatives in Children: A
      Comprehensive Review.
AB  - Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent
      opioids. A comprehensive review of the use of fentanyl and its derivatives in the
      pediatric population was performed using the National Library of Medicine PubMed.
      Studies were included if they contained original pharmacokinetic parameters or
      models using established routes of administration in patients younger than 18
      years of age. Of 372 retrieved articles, 44 eligible pharmacokinetic studies
      contained data of 821 patients younger than 18 years of age, including more than
      46 preterm infants, 64 full-term neonates, 115 infants/toddlers, 188 children,
      and 28 adolescents. Underlying diagnoses included congenital heart and pulmonary
      disease and abdominal disorders. Routes of drug administration were intravenous,
      epidural, oral-transmucosal, intranasal, and transdermal. Despite extensive use
      in daily clinical practice, few studies have been performed. Preterm and term
      infants have lower clearance and protein binding. Pharmacokinetics was not
      altered by chronic renal or hepatic disease. Analyses of the pooled individual
      patients' data revealed that clearance maturation relating to body weight could
      be best described by the Hill function for sufentanil (R 2 = 0.71, B max 876
      mL/min, K 50 16.3 kg) and alfentanil (R 2 = 0.70, B max (fixed) 420 mL/min, K 50
      28 kg). The allometric exponent for estimation of clearance of sufentanil was
      0.99 and 0.75 for alfentanil clearance. Maturation of remifentanil clearance was
      described by linear regression to bodyweight (R 2 = 0.69). The allometric
      exponent for estimation of remifentanil clearance was 0.76. For fentanyl, linear
      regression showed only a weak correlation between clearance and bodyweight in
      preterm and term neonates (R 2 = 0.22) owing to a lack of data in older age
      groups. A large heterogeneity regarding study design, clinical setting, drug
      administration, laboratory assays, and pharmacokinetic estimation was observed
      between studies introducing bias into the analyses performed in this review. A
      limitation of this review is that pharmacokinetic data, based on different modes
      of administration, dosing schemes, and parameter estimation methods, were
      combined.

PMID- 29178009
TI  - Gap junction channels as potential targets for the treatment of major depressive
      disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) remains a major public health problem
      worldwide. The association between MDD and the dysfunction of gap junction
      channels (GJCs) in glial cells, especially astrocytes, is still controversial.
      OBJECTIVE: This review provides an overview of the role of astrocyte GJCs in
      LMDD. RESULTS: Exposure to chronic unpredictable stress caused a reduction in
      connexin expression in the rat prefrontal cortex, a result that is consistent
      with clinical findings reported in postmortem studies of brains from MDD
      patients. Chronic antidepressant treatment in these rats increased the expression
      of connexins. However, pharmacological GJC blockade in normal rodents decreased
      connexin expression and caused depressive-like behaviors. Furthermore, GJC
      dysfunction affects electrical conductance, metabolic coupling and secondary
      messengers, and inflammatory responses, which are consistent with current
      hypotheses on MDD. All these results provide a comprehensive overview of the
      neurobiology of MDD. CONCLUSION: This review supports the hypothesis that the
      regulation of GJCs between astrocytes could be an underlying mechanism for the
      therapeutic effect of antidepressants.

PMID- 29178011
TI  - Pyridoxine-dependent epilepsies: an observational study on clinical, diagnostic,
      therapeutic and prognostic features in a pediatric cohort.
AB  - The aim of our study was to describe the clinical, electroencephalogram,
      molecular findings and the diagnostic and therapeutic flow-chart of children with
      pyridoxine-dependent epilepsies (PDEs). We performed a retrospective
      observational study on children with PDEs, diagnosed and followed-up in Italian
      Pediatric Departments. In each centre, the authors collected data from a cohort
      of children admitted for intractable seizures, responsive to pyridoxine
      administration and resistant to other anticonvulsant therapies. Data were
      retrospectively analysed from January 2016 to January 2017. Sixteen patients (13
      males, and 3 females) were included. We found that 93.75% of patients underwent
      conventional anticonvulsant therapy before starting pyridoxine administration and
      62.5% had ex-juvantibus diagnosis, as specific serum diagnostic tests had been
      performed in only 37.5% of patients by alpha-AASA and pipecolic acid blood and
      urine dosage. The most common type of seizure was generalized tonic-clonic in 7
      patients and the most common EEG pattern was characterized by a "burst
      suppression" pattern. Before pyridoxine administration, other anticonvulsant
      drugs were used in 93.75% of patients, with consequent onset of drug-resistance.
      Phenobarbital was the most frequently used drug as first-line treatment. The
      importance of our study relies on the need of a deeper knowledge of PDEs in terms
      of early diagnosis, avoiding incorrect treatment and related adverse events,
      clinical and EEG pathognomonic features, and genetic aspects of the disease.

PMID- 29178010
TI  - Psychedelics and reconsolidation of traumatic and appetitive maladaptive
      memories: focus on cannabinoids and ketamine.
AB  - RATIONALE: Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post
      traumatic stress disorder (PTSD) patients recently stimulated interest on the
      potential therapeutic use of psychedelics in disorders characterized by
      maladaptive memories, including substance use disorders (SUD). The rationale for
      the use of MDMA in PTSD and SUD is being extended to a broader beneficial
      "psychedelic effect," which is supporting further clinical investigations, in
      spite of the lack of mechanistic hypothesis. Considering that the retrieval of
      emotional memories reactivates specific brain mechanisms vulnerable to
      inhibition, interference, or strengthening (i.e., the reconsolidation process),
      it was proposed that the ability to retrieve and change these maladaptive
      memories might be a novel intervention for PTSD and SUD. The mechanisms
      underlying MDMA effects indicate memory reconsolidation modulation as a
      hypothetical process underlying its efficacy. OBJECTIVE: Mechanistic and clinical
      studies with other two classes of psychedelic substances, namely cannabinoids and
      ketamine, are providing data in support of a potential use in PTSD and SUD based
      on the modulation of traumatic and appetitive memory reconsolidation,
      respectively. Here, we review preclinical and clinical data on cannabinoids and
      ketamine effects on biobehavioral processes related to the reconsolidation of
      maladaptive memories. RESULTS: We report the findings supporting (or not) the
      working hypothesis linking the potential therapeutic effect of these substances
      to the underlying reconsolidation process. We also proposed possible approaches
      for testing the use of these two classes of drugs within the current paradigm of
      reconsolidation memory inhibition. CONCLUSIONS: Metaplasticity may be the process
      in common between cannabinoids and ketamine/ketamine-like substance effects on
      the mediation and potential manipulation of maladaptive memories.

PMID- 29178012
TI  - Administration of Allium cepa L. bulb attenuates stress-produced anxiety and
      depression and improves memory in male mice.
AB  - In view of anxiolytic, antidepressant and memory strengthen properties of Allium
      cepa (AC; onion) bulb in various investigations; we aimed to evaluate the useful
      effects of onion on single immobilization stress -induced biochemical and
      behavioral changes. Mice in test group were treated with AC powder (200
      mg/kg/day), dissolved in water, while the control group were received drinking
      water for 14 days. After 14 days control and AC treated mice were further divided
      into unstressed and stressed groups. Animals in the stressed group were subjected
      to immobilization stress for 2 h. 24-h after the immobilization stress,
      behavioral activities were monitored. Immobilization stress-induced an anxiogenic
      behavior in mice subjected to elevated plus maze test (EPM) and light dark
      activity test (LDA). 2-h immobilization stress-induced depressive behavior in
      animals measured by forced swim test (FST). Administration of AC attenuated the
      immobilization stress-induced behavioral deficits. Highest memory performance was
      observed in stressed mice that were pre-treated with AC in Morris water maze
      (MWM). Brain lipid peroxidation, antioxidant enzymes (SOD, CAT, GPx) and
      acetylcholinesterase (AChE) activities were also estimated. Present study
      suggests a role of antioxidant enzymes in the attenuation of 2-h stress induced
      anxiety and depression, and enhanced cognitive function as well by AC. The
      findings therefore suggest that supplementation of AC may be beneficial in the
      treatment of anxiety, depression and enhancement of memory function.

PMID- 29178013
TI  - Research on the ability of propionic acid and vitamin B12 biosynthesis by
      Propionibacterium freudenreichii strain T82.
AB  - The purpose of this study was to determine the potential for biosynthesis of
      propionic acid and vitamin B12 by Propionibacterium freudenreichii T82 in a
      medium containing various sources of carbon (glucose, fructose, and saccharose).
      These sugars are present in apple pomaces, which are the waste from the
      production of apple juice. Using statistical analysis design of experiments
      (DoE), the results allowed us to determine which sugars (carbon sources) exert
      the most beneficial influence on the biosynthesis of propionic acid and
      cobalamin. The highest production of propionic acid by the tested bacterial
      strain was obtained in a medium in which glucose accounted for at least 50% of
      the available carbon sources. Depending on the culture medium, the concentration
      of this metabolite ranged from 23 to 40 g/L. P. freudenreichii T82 produced the
      smallest amount of acid in medium in which the dominant nutrient source was
      saccharose. The results obtained indicated an inverse relationship between the
      amount of acid produced by the bacteria and vitamin B12 biosynthesis. Because of
      the high efficiency of propionic acid biosynthesis by P. freudenreichii T82, the
      prospect of using this strain to obtain propionate with the simultaneous disposal
      of waste materials (such as apple pomaces) which contain glucose and/or fructose
      is very promising.

PMID- 29178014
TI  - A critical approach to the toxic metal ion removal by hazelnut and almond shells.
AB  - The adsorption capacity of ground hazelnut (HS) and almond (AS) shells towards
      Pb(II) and Cd(II) has been studied at pH = 5, in NaNO3 and NaCl ionic media, in
      the ionic strength range 0.05-0.5 mol L-1. Kinetic and equilibrium experiments
      were carried out by using the Differential Pulse Anodic Stripping Voltammetry
      technique to check the amount of the metal ion removed by HS and AS materials.
      Different kinetic and equilibrium equations were used to fit experimental data
      and a statistical study was done to establish the suitable model for the data
      fitting. A speciation study of the metal ions in solution was also done in order
      to evaluate the influence of the ionic medium on the adsorption process. TGA-DSC,
      FT-IR, and SEM-EDX techniques were used to characterize the adsorbent materials.
      The mechanism of metal ions adsorption was explained on the basis of the results
      obtained by the metal ions speciation study and the characterization of
      materials.

PMID- 29178015
TI  - Spatiotemporal variation and exposure risk to human health of potential toxic
      elements in suburban vegetable soils of a megacity, SW China, 2012-2016.
AB  - Trace element contamination in soils of vegetable fields can threat public
      health. Seven potential toxic elements (As, Cd, Cr, Cu, Ni, Pb, and Zn) in
      suburban vegetable soils of Chengdu city, Southwest China, in 2012 and 2016, were
      analyzed to identify their sources with the spatiotemporal variation and assess
      their contamination and health risk for residents. The results showed that the
      concentrations of soil elements did not increase significantly in 2016 compared
      with that in 2012, whereas their spatial distributions altered markedly. The hot
      spots of soil As, Cd, and Pb as well as Cu and Zn in 2016 revealed the
      anthropogenic sources including agricultural activities, industrial emissions,
      road dust with heavy traffic, and open burning of solid waste. The apparent
      spatial difference of anthropogenic elements was related to the layout of land
      use surrounding the vegetable field. The contamination of soil elements decreased
      in the order of Cd > As ~ Zn > Cu ~ Pb > Cr ~ Ni in 2012 and Cd > Zn > As ~ Cu ~
      Pb > Cr ~ Ni in 2016, and the vegetable soils were slightly to moderately
      contaminated by these elements through integrated contamination index. The sites
      affected by the trace elements did not increase in 2016 than in 2012, whereas the
      sites with relatively high contamination increased markedly. The non-carcinogenic
      risk of trace elements was generally acceptable, and children showed higher
      health risk than adults. The As carcinogenic risk for children varied between
      5.48 * 10-5 and 1.59 * 10-4 in 2012 and between 4.40 * 10-5 and 1.82 * 10-4 in
      2016, and the sites above acceptable levels (> 10-4) reached 60.6% and 48.5% in
      2012 and 2016, respectively. The health risk of As in the vegetable soils should
      be paid more attention due to its high toxicity.

PMID- 29178016
TI  - Adsorption of cesium ion by marine actinobacterium Nocardiopsis sp. 13H and their
      extracellular polymeric substances (EPS) role in bioremediation.
AB  - This paper evaluates the cesium adsorption of marine actinobacterium Nocardiposis
      sp. 13H strain isolated from nuclear power plant sites in India. It could remove
      88.6 +/- 0.72% of Cs+ from test solution containing 10 mM CsCl2. The biosorption
      of Cs+ with different environmental factors such as pH, temperature, and time
      interval is also determined. Scanning electron microscopy coupled with energy
      dispersive spectroscopy (EDS) confirmed the Cs+ adsorption by Nocardiopsis sp.
      13H. Most of the bound cesium was found to be associated extracellular polymeric
      substances (EPS) suggesting its interaction with the surface active groups. The
      main component of the EPS was carbohydrate followed by protein and nucleic acid.
      Further, Fourier transform infrared (FTIR) spectroscopy suggested the carboxyl,
      hydroxyl, and amide groups on the strain cell surface were likely to be involved
      in Cs+ adsorption. Results from this study show Nocardiopsis sp. 13H
      microorganism could be useful in exploring the biosorption of radioisotope
      pollution and developing efficient and eco-friendly biosorbent for environmental
      cleanup.

PMID- 29178017
TI  - Study on the influential biochemical indices of Cd(II) on Eisenia fetida in
      oxidative stress by principal component analysis in the natural soil.
AB  - With the aggravation of heavy metal pollution in soil, the individual heavy metal
      content monitoring cannot predict the true effects of harmful substances on the
      ecosystems. Thus, the effective biological evaluation system should be
      established to assess the pollution risk caused by heavy metal. Earthworms are
      widely distributed in the soil, and at the bottom of the food chain, the changes
      of biochemical indices play an important role in the early warning for heavy
      metal pollution. Principal component analysis (PCA) is a statistical method that
      derives several independent principal components from the original variable based
      on retaining the information as much as possible. This paper is aimed at finding
      out and analyzing the key monitoring factors related to Cd2+ on the earthworm
      Eisenia fetida in oxidative stress. The Cd2+ stress concentrations were set at 0,
      1, 10, 20, 100, 200, 400, and 800 mg kg-1, and the post-clitellum segment of
      earthworm was chosen to determine TP, POD, SOD, GST, GPX, CAT, MDA, VE, and AChE.
      The results showed that the main bioindicators associated with oxidative stress
      reaction were GST, POD, and MDA at the exposure time of 10 days; at 20 days GPX,
      MDA, and AChE; at 30 days CAT, TP, and GPX; CAT, MDA, and SOD at 40th day. These
      results indicated that PCA can quickly, effectively, directly, and scientifically
      select biomarkers of oxidative stress induced by Cd and improve the accuracy and
      scientificity of earthworm as a biomarker in monitoring and early warning for
      heavy metal-contaminated soil.

PMID- 29178018
TI  - Cu(II)-catalyzed degradation of ampicillin: effect of pH and dissolved oxygen.
AB  - Cu(II)-catalyzed hydrolysis of beta-lactam antibiotics has been well-identified
      and recognized as the key mechanism of antibiotic degradation. However, the
      overlooked Cu(II) oxidation susceptibly also plays an important role comparably
      with hydrolysis. This study evaluated the roles of hydrolysis and oxidation in
      Cu(II)-catalyzed degraded ampicillin (AMP), as a typical beta-lactam antibiotic,
      under relevant environmental conditions (pH 5.0, 7.0, and 9.0; oxygen 0.2 and 6.2
      mg/L). Under AMP and Cu(II) molar ratio of 1:1, AMP degradation was the fastest
      at pH 9.0, followed by pH 5.0 and pH 7.0. The facilitation of oxygen on AMP
      degradation was notable at pH 5.0 and 7.0 rather than pH 9.0. AMP degradation
      rate increased from 21.8% in 0.2 mg/L O2 solution to 85.9% in 6.2 mg/L O2
      solution at pH 7.0 after 4-h reaction. AMP oxidation was attributed to both
      oxygen-derived Cu(I)/Cu(II) cycle and intermediate reactive oxygen species (HO.
      and O2.-). Several intermediate and final products in AMP degradation were
      firstly identified by LC-quadrupole time-of-flight-MS analysis. Phenylglycine
      primary amine on the AMP structure was the essential complexation site to proceed
      with the oxidation reaction. The oxidation of AMP preferentially occurred on the
      beta-lactam structure. The inherent mechanisms related to pH and oxygen
      conditions were firstly investigated, which could enhance the understanding of
      both oxidation and hydrolysis mechanisms in AMP degradation. This study not only
      has an important implication in predicting beta-lactam antibiotic transformation
      and fate in natural environment but also benefits the developing of strategies of
      antibiotic control to reduce the environmental risk.

PMID- 29178020
TI  - Author Correction: A novel oocyte maturation trigger using 1500 IU of human
      chorionic gonadotropin plus 450 IU of follicle-stimulating hormone may decrease
      ovarian hyperstimulation syndrome across all in vitro fertilization stimulation
      protocols.
AB  - The original version of this article unfortunately contained a mistake. The
      middle initial of Douglas A. Mata was omitted. The original article has been
      corrected.

PMID- 29178019
TI  - Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine
      resistant advanced breast cancer in routine clinical practice.
AB  - INTRODUCTION: This study aimed to describe the efficacy of fulvestrant 500 mg in
      postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic
      breast cancer who had disease progression after receiving anti-estrogen therapy
      in clinical practice, getting real-world data. MATERIALS AND METHODS:
      Multicenter, retrospective, observational study conducted in Spain.
      Postmenopausal women with locally advanced/metastatic ER-positive breast cancer
      who received treatment with fulvestrant 500 mg after progression with a previous
      anti-estrogen therapy were eligible. The primary endpoint was progression-free
      survival (PFS); secondary endpoints were overall survival (OS), clinical benefit
      rate (CBR), duration of clinical benefit (DoCB), and safety profile. RESULTS: A
      total of 263 women were evaluated (median age, 65.8 years). At a median follow-up
      of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS
      according to 1st, 2nd, 3rd, and >= 4th lines were 11.5, 10.6, 9.9, and 8.5
      months, respectively (p = 0.0245). PFS in patients with visceral involvement was
      10 months vs 10.6 months in patients without visceral involvement (p = 0.6604),
      9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p =
      0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p =
      0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently
      adverse events were injection site pain (10.3%) and musculoskeletal disorders
      (7.6%). CONCLUSIONS: Fulvestrant 500 mg administered in clinical practice was
      shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in
      accordance with previous trials.

PMID- 29178022
TI  - Erratum to: Drebrin - From Structure and Function to Physiological and
      Pathological Roles.

PMID- 29178021
TI  - Epigenetic Drivers in Pediatric Medulloblastoma.
AB  - Epigenetics is the process by which gene expression is regulated by events other
      than alterations of the genome. This includes DNA methylation, histone
      modifications, chromatin remodeling, microRNAs, and long non-coding RNAs.
      Methylation of DNA, chromatin remodeling, and histone modifications regulate the
      chromatin and access of transcription factors to DNA and in turn gene
      transcription. Alteration of chromatin is now recognized to be deregulated in
      many cancers. Medulloblastoma is an embryonal tumor of the cerebellum and the
      most common malignant brain tumor in children, that occurs only rarely in adults.
      Medulloblastoma is characterized by four major molecularly and
      histopathologically distinct groups, wingless (WNT), sonic hedgehog (SHH), group
      3 (G3), and group 4 (G4), that, except for WNT, are each now subdivided in
      several subgroups. Gene expression array, next-generation sequencing, and
      methylation profiling of several hundred primary tumors by several consortia and
      independent groups revealed that medulloblastomas harbor a paucity of mutations
      most of which occur in epigenetic regulators, genetic alterations in oncogenes
      and tumor suppressors, in addition to copy number alterations and chromosome
      gains and losses. Remarkably, some tumors have no reported mutations, suggesting
      that some genes required for oncogenesis might be regulated by epigenetic
      mechanisms which are still to be uncovered and validated. This review will
      highlight several epigenetic regulators focusing mainly on histone modifiers
      identified in medulloblastoma.

PMID- 29178023
TI  - Emotion Self-Regulation Moderates the Association Between Symptoms of ADHD and
      Weight Loss After Bariatric Surgery.
AB  - BACKGROUND: This study aimed to examine the combined effect of pre-surgical
      emotion self-regulation (ESR) and symptoms of attention deficit hyperactivity
      disorder (sADHD, i.e., inattention, impulsivity, and hyperactivity) on weight
      loss 12 months following bariatric surgery independent of psychological distress
      and eating pathology. METHODS: Adults with obesity were recruited from a
      bariatric surgery specialty clinic in Canada. Patients completed measures of
      psychological distress (i.e., Beck Depression Inventory II and Beck Anxiety
      Inventory), eating pathology (i.e., Eating Disorder Examination Questionnaire),
      ESR (i.e., "Managing Own Emotions" subscale of the Schutte Emotional Intelligence
      Test), and sADHD (i.e., Adult ADHD Self-Report Scale) prior to surgery. Measures
      of height and weight were obtained and used to calculate percent excess weight
      loss (%EWL) of body mass index (BMI) pre- and 12 months post-surgery. RESULTS:
      Thirty-seven patients were recruited. The final sample consisted of 30 patients
      (80% female; mean age = 48 years; mean BMI = 49.32). Patients experienced
      significant weight loss and reported significant improvement in anxiety,
      depressed mood, and eating pathology from pre- to 12 months post-surgery. A
      significant sADHD by ESR interaction on %EWL (F(1, 21) = 6.43, p = .019) was
      observed and accounted for 13% of unique variance after adjusting for relevant
      covariates. Probing the interaction with the Johnson-Neyman technique indicated
      that there was a significant inverse association between sADHD and %EWL among
      individuals who scored <= 0.15 SD below the mean on ESR. CONCLUSIONS: ESR
      moderated the association between sADHD and %EWL, suggesting that sADHD may
      attenuate weight loss following bariatric surgery among individuals deficient in
      ESR. This finding has implications for bariatric surgery pre-surgical
      psychological assessment.

PMID- 29178025
TI  - Pegylated Liposomal Irinotecan Hydrochloride Trihydrate for Treating Pancreatic
      Cancer After Gemcitabine: An Evidence Review Group Perspective of a NICE Single
      Technology Appraisal.
AB  - The National Institute for Health and Care Excellence (NICE) invited the
      manufacturer (Shire Pharmaceuticals) of pegylated liposomal irinotecan
      hydrochloride trihydrate (liposomal irinotecan) to submit clinical and cost
      effectiveness evidence for its use in combination with 5-fluorouracil (5-FU) and
      folic acid/leucovorin (LV) for treating patients with pancreatic cancer following
      prior treatment with gemcitabine as part of the institute's Single Technology
      Appraisal process. The Liverpool Reviews and Implementation Group at the
      University of Liverpool was commissioned to act as the Evidence Review Group
      (ERG). This article presents a summary of the company's evidence, the ERG review
      and the resulting NICE guidance (TA440), issued on 26 April 2017. Clinical
      evidence for liposomal irinotecan + 5-FU/LV versus 5-FU/LV was derived from 236
      patients with metastatic pancreatic cancer in the multinational, open-label,
      randomised controlled NAPOLI-1 trial. Results from analyses of progression-free
      survival and overall survival showed statistically significant improvements for
      patients treated with liposomal irinotecan + 5-FU/LV compared with those treated
      with 5-FU/LV. However, 5-FU/LV alone is rarely used in National Health Service
      clinical practice for patients with metastatic pancreatic cancer previously
      treated with gemcitabine. The company, ERG and Appraisal Committee (AC) all
      agreed that oxaliplatin + 5-FU/LV is the most commonly used treatment.
      Oxaliplatin + 5-FU/LV was compared with 5-FU/LV in two trials identified by the
      company. However, the company and the ERG both considered attempts to compare the
      efficacy of liposomal irinotecan + 5-FU/LV with oxaliplatin + 5-FU/LV to be
      methodologically flawed; not only was there heterogeneity between trials and
      their populations but also the proportional hazards assumption required to
      conduct a robust indirect treatment comparison (ITC) was violated. Nonetheless,
      data derived from an ITC were used to inform the company's economic model. Using
      the discounted patient access scheme price for liposomal irinotecan + 5-FU/LV,
      the company reported an incremental cost-effectiveness ratio (ICER) per quality
      adjusted life-year (QALY) gained of L54,412 for the comparison with oxaliplatin +
      5-FU/LV. The ERG considered that the company's base-case cost-effectiveness
      results for the comparison of liposomal irinotecan + 5-FU/LV versus oxaliplatin +
      5-FU/LV were underestimates and should be interpreted with extreme caution.
      Following implementation of a number of model amendments, the ERG's modified
      exploratory ICER for the comparison of liposomal irinotecan + 5-FU/LV versus
      oxaliplatin + 5-FU/LV was L106,898 per QALY gained. The AC accepted the majority
      of the ERG's amendments to the model, and also highlighted that the total QALYs
      for oxaliplatin + 5-FU/LV were lower than for 5-FU/LV in the company's model,
      which the AC considered to be clinically implausible. The AC therefore considered
      results from exploratory analyses, undertaken by the ERG, which included altering
      the QALY difference between liposomal irinotecan + 5-FU/LV and oxaliplatin + 5
      FU/LV by +/- 10%. These analyses resulted in ICERs for the comparison of
      liposomal irinotecan + 5-FU/LV versus oxaliplatin + 5-FU/LV of between L201,019
      per QALY gained to liposomal irinotecan + 5-FU/LV being dominated by oxaliplatin
      + 5-FU/LV. Therefore, despite uncertainty around the clinical-effectiveness
      evidence and cost-effectiveness results, the AC was confident that the ICER was
      in excess of L50,000 per QALY gained. The final guidance issued by NICE is that
      liposomal irinotecan + 5-FU/LV is not recommended within its marketing
      authorisation for treating metastatic adenocarcinoma of the pancreas in adults
      whose disease has progressed after gemcitabine-based therapy.

PMID- 29178024
TI  - Does EGFR Mutation Type Influence Patient-Reported Outcomes in Patients with
      Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer? Analysis of Two
      Large, Phase III Studies Comparing Afatinib with Chemotherapy (LUX-Lung 3 and LUX
      Lung 6).
AB  - INTRODUCTION: In LUX-Lung 3 and LUX-Lung 6, afatinib significantly improved
      progression-free survival (PFS) versus chemotherapy in patients with tumors
      harboring common epidermal growth factor receptor (EGFR) mutations (Del19/L858R)
      and significantly improved overall survival (OS) in patients with tumors
      harboring Del19 mutations. Patient-reported outcomes stratified by EGFR mutation
      type are reported. PATIENTS AND METHODS: Lung cancer symptoms and health-related
      quality of life (QoL) were assessed every 21 days until progression using the
      EORTC Quality of Life Core Questionnaire C30 and its lung cancer-specific module,
      LC13. Analyses of cough, dyspnea, and pain were prespecified and included
      analysis of percentage of patients who improved on therapy, time to deterioration
      of symptoms, and change over time. Global health status (GHS)/QoL was also
      assessed. Analyses were conducted for all patients with tumors harboring Del19 or
      L858R mutations and were exploratory. RESULTS: Compared with chemotherapy,
      afatinib more commonly improved symptoms of, delayed time to deterioration for,
      and was associated with better mean scores over time for cough and dyspnea in
      patients with Del19 or L858R mutations. All three prespecified analyses of pain
      showed a trend favoring afatinib over chemotherapy. In both Del19 and L858R
      mutations, afatinib was also associated with improvements in GHS/QoL.
      Longitudinal analyses demonstrated statistically significant improvements in
      GHS/QoL for afatinib over chemotherapy for patients with tumors harboring Del19
      mutations or L858R mutations. CONCLUSIONS: These exploratory analyses suggest
      first-line afatinib improved lung cancer-related symptoms and GHS/QoL compared
      with chemotherapy in patients with non-small-cell lung cancer with tumors
      harboring common EGFR mutations, with benefits in both Del19 and L858R patients.
      When considered with OS (Del19 patients only) and PFS benefits, these findings
      substantiate the value of using afatinib over chemotherapy in these patient
      groups.

PMID- 29178026
TI  - Inorganic mercury in mammary cells: viability, metal uptake but efflux?
AB  - The viability, cellular uptake and subcellular distribution of heavy metal Hg,
      were determined in human mammary cell lines (MCF-7, MDA-MB-231 and MCF-10A). It
      was observed that Hg had the capacity of being excluded from the cells with a
      different type of possible transporters. MCF-7 cells showed the lowest viability,
      while the other two cell lines were much more resistant to Hg treatments. The
      intracellular concentration of Hg was higher at lower exposure times in MCF-10A
      cells and MCF-7 cells; but as the time was increased only MDA-MB-231 showed the
      capacity to continue introducing the metal. In MCF-7 and MCF-10A cells the
      subcellular distribution of Hg was higher in cytosolic fraction than nucleus and
      membrane, but MDA-MB-231 showed membrane and nucleus fraction as the enriched
      one. The analysis of RNA-seq about the genes or family of genes that encode
      proteins which are related to cytotoxicity of Hg evidenced that MCF-10A cells and
      MCF-7 cells could have an active transport to efflux the metal. On the contrary,
      in MDA-MB-231 no genes that could encode active transporters have been found.

PMID- 29178027
TI  - MRI Guiding of the Middle Cerebral Artery Occlusion in Rats Aimed to Improve
      Stroke Modeling.
AB  - The middle cerebral artery occlusion (MCAO) model in rats closely imitates
      ischemic stroke and is widely used. Existing instrumental methods provide a
      certain level of MCAO guidance, but monitoring of the MCA-occluding intraluminal
      filament position and possible complications can be improved. The goal of this
      study was to develop a MRI-based method of simultaneous control of the filament
      position, blood flow in the intracranial vessels, and hemorrhagic complications.
      Rats were subjected to either MRI-guided MCAO (group 1, n = 51) or MCAO without
      MRI control (group 2, n = 38). After operation, group 1 rats were transferred
      into a MRI scanner for the control of the filament position and possible
      complications. Ninety minutes after the onset of MCAO, the filament was removed
      in rats of both groups and MRI control of the infarct volume and hemorrhagic
      complications performed. High-resolution T1- and T2-weighted imaging performed
      immediately after filament insertion provided visualization of the filament
      position, blood flow in brain arteries, and complications related to
      inappropriate filament insertion. It permitted replacement of wrongly positioned
      filaments and exclusion of animals with complications from the experiment. MRI
      based MCAO guiding provided real-time intra-operational monitoring of crucial
      parameters determining MCAO suitability for stroke modeling, including better
      assessment of the operation outcomes in individual animals and significant
      enhancement of the model success rate. The possibility of simultaneous
      visualization of the filament, blood flow in the arteries, brain tissue, and
      hemorrhagic complications is the principal advantage of the proposed method over
      other instrumental methods of MCAO quality control. Graphical Abstract MRI-guided
      middle cerebral artery occlusion technique permits intra-operational monitoring
      via direct non-invasive simultaneous visualization of the filament, blood flow in
      the arteries, brain tissue, and hemorrhagic complications. It provides better
      assessment of MCAO outcomes in individual animals and significant enhancement of
      MCAO success rate.

PMID- 29178028
TI  - Non-invasive measurement of liver iron concentration using 3-Tesla magnetic
      resonance imaging: validation against biopsy.
AB  - OBJECTIVES: To evaluate the performance and limitations of the R2* and signal
      intensity ratio (SIR) methods for quantifying liver iron concentration (LIC) at 3
      T. METHODS: A total of 105 patients who underwent a liver biopsy with biochemical
      LIC (LICb) were included prospectively. All patients underwent a 3-T MRI scan
      with a breath-hold multiple-echo gradient-echo sequence (mGRE). LIC calculated by
      3-T SIR algorithm (LICSIR) and by R2* (LICR2*) were correlated with LICb.
      Sensitivity and specificity were calculated. The comparison of methods was
      analysed for successive classes. RESULTS: LICb was strongly correlated with R2*
      (r = 0.95, p < 0.001) and LICSIR (r = 0.92, p < 0.001). In comparison to LICb,
      LICR2* and LICSIR detect liver iron overload with a sensitivity/specificity of
      0.96/0.93 and 0.92/0.95, respectively, and a bias +/- SD of 7.6 +/- 73.4 and 14.8
      +/- 37.6 MUmol/g, respectively. LICR2* presented the lowest differences for
      patients with LICb values under 130 MUmol/g. Above this value, LICSIR has the
      lowest differences. CONCLUSIONS: At 3 T, R2* provides precise LIC quantification
      for lower overload but the SIR method is recommended to overcome R2* limitations
      in higher overload. Our software, available at www.mrquantif.org , uses both
      methods jointly and selects the best one. KEY POINTS: * Liver iron can be
      accurately quantified by MRI at 3 T * At 3 T, R2* provides precise quantification
      of slight liver iron overload * At 3 T, SIR method is recommended in case of high
      iron overload * Slight liver iron overload present in metabolic syndrome can be
      depicted * Treatment can be monitored with great confidence.

PMID- 29178029
TI  - Chemical shift magnetic resonance imaging for distinguishing minimal-fat renal
      angiomyolipoma from renal cell carcinoma: a meta-analysis.
AB  - OBJECTIVES: To determine the performance of chemical shift signal intensity index
      (CS-SII) values for distinguishing minimal-fat renal angiomyolipoma (mfAML) from
      renal cell carcinoma (RCC) and to assess RCC subtype characterisation. METHODS:
      We identified eligible studies on CS magnetic resonance imaging (CS-MRI) of focal
      renal lesions via PubMed, Embase, and the Cochrane Library. CS-SII values were
      extracted by lesion type and evaluated using linear mixed model-based meta
      regression. RCC subtypes were analysed. Two-sided p value <0.05 indicated
      statistical significance. Methodological quality was assessed using the Quality
      Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Eleven articles
      involving 850 patients were included. Minimal-fat AML had significantly higher CS
      SII value than RCC (p < 0.05); there were no significant differences between
      mfAML and clear cell RCC (cc-RCC) (p = 0.112). Clear cell RCC had a significantly
      higher CS-SII value than papillary RCC (p-RCC) (p < 0.001) and chromophobe RCC
      (ch-RCC) (p = 0.045). The methodological quality was relatively high, and Begg's
      test data points indicated no obvious publication bias. CONCLUSIONS: The CS-SII
      value for differentiating mfAML from cc-RCC remains unproven, but is a promising
      method for differentiating cc-RCC from p-RCC and ch-RCC. KEY POINTS: * RCC CS-SII
      values are significantly lower than those of mfAML overall. * CS-SII values
      cannot aid differentiation between mfAML and cc-RCC. * CS-SII values might help
      characterise RCC subtypes.

PMID- 29178030
TI  - Sensitivity to change and association of three-dimensional meniscal measures with
      radiographic joint space width loss in rapid clinical progression of knee
      osteoarthritis.
AB  - OBJECTIVE: To determine whether 3D meniscal measures had similar sensitivity to
      longitudinal change as cartilage thickness; to what extent these measures are
      associated with longitudinal joint space width (JSW) change; and whether the
      latter associations differ between minimum (mJSW) and fixed-location JSW.
      METHODS: Two-year changes in medial meniscal position and morphology, cartilage
      thickness (MRI) and minimum and fixed-location JSW (radiography) were determined
      in 35 Osteoarthritis Initiative knees [12 men, age: 67 (51-77) years; 23 women,
      age: 65 (54-78) years], progressing from baseline Kellgren-Lawrence grade <=2 to
      knee replacement within 3-5 years. Multiple linear regression assessed the
      features contributing to JSW change. RESULTS: Meniscal measures, cartilage
      thickness and JSW displayed similar sensitivity to change (standardised response
      mean<=|0.76|). Meniscal changes were strongly associated with JSW change
      (r<=|0.66|), adding <=20% to its variance in addition to cartilage thickness
      change. Fixed-location JSW change (multiple r2=72%) was more strongly related to
      cartilage and meniscal change than mJSW (61%). Meniscal morphology explained more
      of fixed-location JSW and meniscal position more of mJSW. CONCLUSION: Meniscal
      measures provide independent information in explaining the variance of
      radiographic JSW change. Fixed-location JSW appears to be more reflective of
      structural change than mJSW and, hence, a potentially superior measure of
      structural progression. KEY POINTS: * 3D positional/morphological meniscal
      measures change in rapidly progressing knees. * Similar sensitivity to 2-year
      change of quantitative meniscal/cartilage measures in rapid progression. *
      Changes in meniscal measures are strongly associated with radiographic JSW
      change. * Meniscal change provides information to explain JSW variance
      independent of cartilage. * Fixed-location JSW reflects structural disease stage
      more closely than minimum JSW.

PMID- 29178032
TI  - Lithium increases ammonium excretion leading to altered urinary acid-base buffer
      composition.
AB  - Previous reports identify a voltage dependent distal renal tubular acidosis
      (dRTA) secondary to lithium (Li+) salt administration. This was based on the
      inability of Li+-treated patients to increase the urine-blood (U-B) pCO2 when
      challenged with NaHCO3 and, the ability of sodium neutral phosphate or Na2SO4
      administration to restore U-B pCO2 in experimental animal models. The underlying
      mechanisms for the Li+-induced dRTA are still unknown. To address this point, a 7
      days time course of the urinary acid-base parameters was investigated in rats
      challenged with LiCl, LiCitrate, NaCl, or NaCitrate. LiCl induced the largest
      polyuria and a mild metabolic acidosis. Li+-treatment induced a biphasic
      response. In the first 2 days, proper urine volume and acidification occurred,
      while from the 3rd day of treatment, polyuria developed progressively. In this
      latter phase, the LiCl-treated group progressively excreted more NH4+ and less
      pCO2, suggesting that NH3/NH4+ became the main urinary buffer. This physiological
      parameter was corroborated by the upregulation of NBCn1 (a marker of increased
      ammonium recycling) in the inner stripe of outer medulla of LiCl treated rats.
      Finally, by investigating NH4+ excretion in ENaC-cKO mice, a model resistant to
      Li+-induced polyuria, a primary role of the CD was confirmed. By definition, dRTA
      is characterized by deficient urinary ammonium excretion. Our data question the
      presence of a voltage-dependent Li+-induced dRTA in rats treated with LiCl for 7
      days and the data suggest that the alkaline urine pH induced by NH3/NH4+ as the
      main buffer has lead to the interpretation dRTA in previous studies.

PMID- 29178031
TI  - A predictive model for distinguishing radiation necrosis from tumour progression
      after gamma knife radiosurgery based on radiomic features from MR images.
AB  - OBJECTIVES: To develop a model using radiomic features extracted from MR images
      to distinguish radiation necrosis from tumour progression in brain metastases
      after Gamma Knife radiosurgery. METHODS: We retrospectively identified 87
      patients with pathologically confirmed necrosis (24 lesions) or progression (73
      lesions) and calculated 285 radiomic features from four MR sequences (T1, T1 post
      contrast, T2, and fluid-attenuated inversion recovery) obtained at two follow-up
      time points per lesion per patient. Reproducibility of each feature between the
      two time points was calculated within each group to identify a subset of features
      with distinct reproducible values between two groups. Changes in radiomic
      features from one time point to the next (delta radiomics) were used to build a
      model to classify necrosis and progression lesions. RESULTS: A combination of
      five radiomic features from both T1 post-contrast and T2 MR images were found to
      be useful in distinguishing necrosis from progression lesions. Delta radiomic
      features with a RUSBoost ensemble classifier had an overall predictive accuracy
      of 73.2% and an area under the curve value of 0.73 in leave-one-out cross
      validation. CONCLUSIONS: Delta radiomic features extracted from MR images have
      potential for distinguishing radiation necrosis from tumour progression after
      radiosurgery for brain metastases. KEY POINTS: * Some radiomic features showed
      better reproducibility for progressive lesions than necrotic ones * Delta
      radiomic features can help to distinguish radiation necrosis from tumour
      progression * Delta radiomic features had better predictive value than did
      traditional radiomic features.

PMID- 29178033
TI  - A review of Neuropathic Pain: From Guidelines to Clinical Practice.
AB  - : Neuropathic pain is a chronic condition representing a significant burden for
      patients, society, and healthcare systems. The prevalence of neuropathic pain in
      the general population has been estimated at 7-8% and is expected to increase in
      the future. Neuropathic pain differs from nociceptive pain and requires a
      different therapeutic approach; and the management of neuropathic pain is
      complicated and challenging. This chapter discusses clinical practice guidelines
      for neuropathic pain and their usefulness in clinical practice. FUNDING: Pfizer,
      Italy.

PMID- 29178034
TI  - Pharmacotherapy for Neuropathic Pain: A Review.
AB  - : Neuropathic pain, comprising a range of heterogeneous conditions, is often
      severe and difficult to manage, and this may result in a chronic condition that
      negatively affects the overall functioning and quality of life in patients. The
      pharmacotherapy of neuropathic pain is challenging and for many patients
      effective treatment is lacking; therefore, evidence-based recommendations are
      essential. Currently, there is general agreement on which drugs are appropriate
      for the first-line treatment of neuropathic pain, whereas debate continues
      regarding second- and third-line treatments. First-line drugs for neuropathic
      pain include antidepressants (tricyclic antidepressants and serotonin
      noradrenaline reuptake inhibitors) and anticonvulsants acting at calcium channels
      (pregabalin and gabapentin). Second- and third-line drugs for neuropathic pain
      include topical lidocaine and opioids. Although efficacious in the treatment of
      neuropathic pain, opioids are not considered to be a first choice because of
      adverse drug reactions and, more recently, because of concerns about abuse,
      diversion, and addiction. A clear understanding of the mechanism of action of
      currently available drugs is an essential step towards an effective clinical
      approach that aims to tailor therapies both to the specific neuropathic disease
      and to the needs of an individual patient. This review provides an overview of
      current drugs available for the treatment of neuropathic pain with an emphasis on
      their mechanism of action. FUNDING: Pfizer, Italy.

PMID- 29178035
TI  - A Review of the Emotional Aspects of Neuropathic Pain: From Comorbidity to Co
      Pathogenesis.
AB  - : Neuropathic pain is characterized by both sensory and affective disturbances,
      supporting the notion that pain and mood disorders share common pathogenetic
      mechanisms. Moreover, biological and neuroimaging data show that common brain
      areas are involved in the modulation of painful and emotional experiences.
      Improved understanding of the molecular mechanisms underlying the role of
      neuroinflammation in regulation of affective behavior in neuropathic pain states
      is important for the development of novel therapeutic strategies. Psychological
      issues must be considered a factor influencing treatment and outcome in patients
      with neuropathic pain. FUNDING: Pfizer, Italy.

PMID- 29178036
TI  - Neuropathic Pain and Sleep: A Review.
AB  - : Neuropathic pain is associated with sleep disturbances, and in turn poor sleep
      quality leads to increased pain sensitivity, so it is essential to assess sleep
      alongside neuropathic pain. Responses to drugs are inconsistent and identifying
      the best treatment option that will reduce pain and improve sleep quality remains
      challenging for clinicians. Anticonvulsants such as pregabalin and gabapentin
      improve neuropathic pain and have a positive effect on comorbid sleep
      disturbances. Opioids and antidepressants are effective in reducing pain but can
      exacerbate sleep disturbances. FUNDING: Pfizer, Italy.

PMID- 29178037
TI  - A Review of Neuropathic Pain: From Diagnostic Tests to Mechanisms.
AB  - : Neuropathic pain develops when the somatosensory nervous system is affected by
      a lesion or disease. Diagnostic tests aimed at assessing somatosensory afferent
      pathway damage are therefore useful for diagnosing neuropathic pain. Neuropathic
      pain manifests with a range of different symptoms such as ongoing burning pain,
      squeezing or pressure pain, paroxysmal electric shock-like sensations, stabbing
      pain, or mechanical dynamic allodynia. The various types of neuropathic pain are
      associated with different underlying nerve fiber abnormalities. This article
      summarizes the available methods of somatosensory afferent pathway assessment and
      discusses the potential pathophysiology underlying the most representative
      neuropathic pain types, i.e., ongoing burning pain, paroxysmal pain, and
      mechanical dynamic allodynia. FUNDING: Pfizer, Italy.

PMID- 29178038
TI  - Neuropathic Pain: The Scope of the Problem.

PMID- 29178039
TI  - Platelet-neutrophil interactions as drivers of inflammatory and thrombotic
      disease.
AB  - Neutrophils are well known for their role in infection and inflammatory disease
      and are first responders at sites of infection or injury. Platelets have an
      established role in hemostasis and thrombosis and are first responders at sites
      of vascular damage. However, neutrophils are increasingly recognized for their
      role in thrombosis, while the immunemodulatory properties of platelets are being
      increasingly studied. Platelets and neutrophils interact during infection,
      inflammation and thrombosis and modulate each other's functions. This review will
      discuss the consequences of platelet-neutrophil interactions in infection,
      thrombosis, atherosclerosis and tissue injury and repair.

PMID- 29178040
TI  - Live imaging analysis of human gastric epithelial spheroids reveals spontaneous
      rupture, rotation and fusion events.
AB  - Three-dimensional cultures of primary epithelial cells including organoids,
      enteroids and epithelial spheroids have become increasingly popular for studies
      of gastrointestinal development, mucosal immunology and epithelial infection.
      However, little is known about the behavior of these complex cultures in their
      three-dimensional culture matrix. Therefore, we performed extended time-lapse
      imaging analysis (up to 4 days) of human gastric epithelial spheroids generated
      from adult tissue samples in order to visualize the dynamics of the spheroids in
      detail. Human gastric epithelial spheroids cultured in our laboratory grew to an
      average diameter of 443.9 +/- 34.6 MUm after 12 days, with the largest spheroids
      reaching diameters of >1000 MUm. Live imaging analysis revealed that spheroid
      growth was associated with cyclic rupture of the epithelial shell at a frequency
      of 0.32 +/- 0.1/day, which led to the release of luminal contents. Spheroid
      rupture usually resulted in an initial collapse, followed by spontaneous re
      formation of the spheres. Moreover, spheroids frequently rotated around their
      axes within the Matrigel matrix, possibly propelled by basolateral pseudopodia
      like formations of the epithelial cells. Interestingly, adjacent spheroids
      occasionally underwent luminal fusion, as visualized by injection of individual
      spheroids with FITC-Dextran (4 kDa). In summary, our analysis revealed unexpected
      dynamics in human gastric spheroids that challenge our current view of cultured
      epithelia as static entities and that may need to be considered when performing
      spheroid infection experiments.

PMID- 29178041
TI  - Cellular immune response in MDR-TB patients to different protein expression of
      MDR and susceptible Mycobacterium tuberculosis: Rv0147, a novel MDR-TB biomarker.
AB  - Tuberculosis (TB) is a crucial public health problem with prevalence of multidrug
      resistant (MDR) rising. An accurate TB biomarker is urgently needed to monitor
      the response to treatment in patients with MDR tuberculosis. To analyze
      interaction between selected MDR-TB purified protein and immune cells, dendritic
      cells from MDR-TB patients and healthy subjects were stimulated by 55KDa protein
      fractions (Rv0147). The purified proteins identified by proteomic techniques (two
      dimensional gel electrophoresis, mass spectrometry) and peptide sequences are
      known to bind a MHC class I alleles which are extracted from the Immune Epitope
      Database and Analysis Resource database ( www.iedb.org ). T cells were isolated
      from PBMC by negative selection and cells were cultured in RPMI-1640 at 37 
      degrees C and 5% CO2. Cell culture was assayed for cytokine IL-10 and INF-gamma
      by ELISA. We found that INF-gamma production was significantly (335 +/- 35.5
      pg/ml, P ? 0.05) upregulated after protein candidate (Rv0147) stimulation by
      dendritic cells from MDR-TB patients, whereas IL-10 production was greatly
      reduced compared with production in healthy subjects (212 +/- 9.94 pg/ml, P ?
      0.05). In fact, the purified protein, Rv0147, stimulated dendritic cells from MDR
      TB patients, failed to produce IL-10 and directly stimulates INF-gamma production
      by T cells. These results suggest that the purified protein, Rv0147, may
      stimulate Th1 type protective cytokine response in MDR-TB patients but not in
      normal subjects. The production of INF-gamma but not IL-10 in the presence of
      purified protein, Rv0147, may be shifted to Th1 responses in MDR-TB patients and
      supports its potential as protein vaccine candidates against TB.

PMID- 29178043
TI  - Intensive care medicine in 2050: nanotechnology. Emerging technologies and
      approaches and their impact on critical care.

PMID- 29178042
TI  - Correction to: Terminal weaning or immediate extubation for withdrawing
      mechanical ventilation in critically ill patients (the ARREVE observational
      study).
AB  - Correction to: Intensive Care Med (2017) DOI 10.1007/s00134-017-4891-0.

PMID- 29178046
TI  - [Dietary efficacy of a micronutrient combination in patients with recurrent upper
      respiratory tract infections. Results of a placebo-controlled doubleblind study.]
AB  - BACKGROUND AND OBJECTIVES: An optimal vitamin and mineral supply may contribute
      to the enhancement of immune defenses and thus favorably influence the course and
      intensity of recurrent upper respiratory tract infections (URIs). In the present
      study the dietary efficacy and benefits of a micronutrient combination in
      patients with recurrent URIs was evaluated. METHODS: 192 patients with recurrent
      URIs were enrolled in this randomized, placebo-controlled, double-blind
      multicenter trial for a study duration of 16 weeks. Efficacy variables were
      number, intensity and course of URIs (as assessed using a total common cold score
      [CCS]) and the alterations in micronutrient supply (vitamins C and D3, folic acid
      and selenium) during the study. RESULTS: In subjects who initially had at least
      two common cold symptoms (N = 107) the symptoms improved in the active group (AG)
      significantly more than in the placebo group (PG; DeltaCCS: AG -6.9 +/- 4.8; PG 
      5.4 +/- 4.5; p = 0.034). In patients with initially severe common cold (CC)
      episodes the symptoms improved in the AG to a statistically significant extent
      (DeltaCCS: AG -93.8%, PG -91.2%, p = 0.043). In the age group below 45 years
      significantly fewer AG than PG patients were absent from their job during the
      second or third CC episode (AG: 14.3%, PG: 47.8%, p = 0.038). Patients with
      vitamin-D deficiency and/or insufficient vitamin-C supply reported significantly
      fewer CC episodes in AG than in PG. In the course of the trial, in AG vs. PG the
      serum vitamin C, folic acid and selenium levels increased (p ? 0.001). The
      concentration of 25(OH)D3 decreased in both groups, but less so in the AG (AG 
      8.8%; PG -14%; p = 0.001). CONCLUSION: Study results show the efficacy of a
      nutritional medical treatment with a special micronutrient combination in
      patients susceptible to infections and suffering from recurrent respiratory tract
      infections.

PMID- 29178044
TI  - Periprosthetic bone remodelling of short-stem total hip arthroplasty: a
      systematic review.
AB  - PURPOSE: Short-stem hip arthroplasty (SHA) was designed to preserve bone stock
      and provide an improved load transfer. To gain more evidence regarding the load
      transfer, this review analysed the periprosthetic bone remodelling of SHA in
      comparison to standard hip arthroplasty (THA). METHODS: PubMed and ScienceDirect
      were screened to extract dual-energy X-ray absorptiometry (DXA) studies
      evaluating the periprosthetic bone remodelling of SHA and two proven THA designs.
      From the studies included, the postoperative change in periprosthetic bone
      mineral density (BMD) after one year and the trend over two years was determined.
      RESULTS: Fifteen studies with four SHAs (CFP, Metha, Nanos, Fitmore) and two THAs
      (CLS and Bicontact) designs were included. All SHA and THA stems revealed an
      initial decrease at the calcar and major trochanter (Gruen 1 and 7) with the
      Metha, Nanos and Fitmore showing a smaller and more balanced remodelling compared
      to THA. The pattern after one year and the trend over two years argue for a
      methaphyseal anchorage of the Metha and Nanos, whereas the Fitmore and CFP seem
      to anchor metha-diaphyseal. Clearly different pattern of bone remodelling were
      observed between all four SHAs. CONCLUSIONS: Periprosthetic bone remodelling is
      also present in SHA, with the main bone reduction observed proximally. However,
      certain SHA stems show a more balanced remodelling compared to THA, arguing for a
      favourable load transfer. Also, the femoral length where bone remodelling occurs
      is clearly shorter in SHA. As distinctively different pattern between the SHA
      designs were observed, they should not be judged as a single implant group.

PMID- 29178047
TI  - [Methods for identification of adverse events of frequent drugs in regulative
      use. Differences between questioning or spontaneous informing of the incidence].

PMID- 29178045
TI  - Considering choline as methionine precursor, lipoproteins transporter, hepatic
      promoter and antioxidant agent in dairy cows.
AB  - During the transition period, fatty liver syndrome may be caused in cows undergo
      negative energy balance, ketosis or hypocalcemia, retained placenta or mastitis
      problems. During the transition stage, movement of non-esterified fatty acids
      (NEFA) increases into blood which declines the hepatic metabolism or reproduction
      and consequently, lactation performance of dairy cows deteriorates. Most of
      studies documented that, choline is an essential nutrient which plays a key role
      to decrease fatty liver, NEFA proportion, improve synthesis of
      phosphatidylcholine, maintain lactation or physiological function and work as
      anti-oxidant in the transition period of dairy cows. Also, it has a role in the
      regulation of homocysteine absorption through betaine metabolite which
      significantly improves plasma alpha-tocopherol and interaction among choline,
      methionine and vitamin E. Many studies reported that, supplementation of rumen
      protected form of choline during transition time is a sustainable method as rumen
      protected choline (RPC) perform diverse functions like, increase glucose level or
      energy balance, fertility or milk production, methyl group metabolism, or
      signaling of cell methionine expansion or methylation reactions, neurotransmitter
      synthesis or betaine methylation, increase transport of lipids or lipoproteins
      efficiency and reduce NEFA or triacylglycerol, clinical or sub clinical mastitis
      and general morbidity in the transition dairy cows. The purpose of this review is
      that to elucidate the choline importance and functions in the transition period
      of dairy cows and deal all morbidity during transition or lactation period.
      Furthermore, further work is needed to conduct more studies on RPC requirements
      in dairy cows ration under different feeding conditions and also to elucidate the
      genetic and molecular mechanisms of choline in ruminants industry.

PMID- 29178048
TI  - [Daily ailments among healthy, middle-aged adults - Situation report and
      explanatory approaches].
AB  - HEADING: Background: Physical performance steadily declines with increasing age
      even among healthy adults. METHODS: A sport scientific screening-battery was used
      to determine the relationship between physical performance - that is endurance,
      strength, coordination, flexibility - and typical daily ailments as measured by a
      questionnaire among 222 healthy, middle-aged women and men. Cardiopulmonary
      performance was estimated by a 2-km walking test. RESULTS: Cardiopulmonary
      performance declined significantly as a result of increasing age and increasing
      body-mass index. 44% of men and 29% of women reached substandard values when
      compared to norm tables. Daily ailments such as "Problems while climbing stairs"
      or "Breathing difficulty" showed a strong correlation to the estimated
      cardiopulmonary performance. In contrast, they were less influenced by strength
      or flexibility. The subjects were oblivious of the relationship between the
      decreased performance of the cardiovascular system and daily ailments.
      CONCLUSION: Performing a simple screening-battery may be a good chance to promote
      the participation of middle-aged and non-athletic people in an adequate and
      health oriented sports program.

PMID- 29178050
TI  - Heat Stress and Agonists of Muscarinic Cholinergic Receptors Modulate Sensitivity
      of Nicotinic Cholinergic Receptors in Soil Nematode Caenorhabditis elegans.
AB  - We studied the effect of moderate heat stress (30oC) and muscarinic cholinergic
      receptor agonists arecoline and pilocarpine on sensitivity of the behavior of the
      nematode Caenorhabditis elegans of N2 line to the action of the agonist of
      nicotinic cholinergic receptor agonist levamisole. Heat stress and muscarinic
      cholinergic receptor agonists increased the sensitivity of swimming induced by
      mechanical stimulation to levamisole (32-64 MUM), which manifested in
      dyscoordination of locomotor muscles during swimming and complete loss of ability
      to swim. Combined exposure to heat stress and muscarinic cholinergic receptor
      agonists revealed their synergism in the influence on sensitivity of swimming
      behavior to levamisole: heating to 30oC potentiated the effect of arecoline and
      arecoline potentiated the effect of heat stress. It is assumed, that the effect
      of heat stress on the sensitivity of nicotinic receptors is mediated by its
      effect on muscarinic receptors.

PMID- 29178049
TI  - AT1 receptor blockage impairs NF-kappaB activation mediated by thyroid hormone in
      cardiomyocytes.
AB  - We have previously demonstrated that calcium-binding protein S100A8 and myeloid
      differentiation factor-88 (MyD88) are important mediators of nuclear
      transcription factor kappa-B (NF-kappaB) activation in cardiomyocytes and that
      signalling molecules are involved in the hypertrophic response that is stimulated
      by thyroid hormones (TH). Angiotensin II (Ang II), the main active peptide of the
      renin-angiotensin system (RAS), binds to type 1 Ang II receptor (AT1R) and
      subsequently promotes cardiac hypertrophy and the inflammatory response with NF
      kappaB activation underlying the cardiovascular effects. Considering the amount
      of evidence that RAS is an important mediator of TH actions on the cardiovascular
      system, we aimed to investigate whether cardiac expression of NF-kappaB and
      upstream associated molecules could be altered in hyperthyroidism, as well as
      whether AT1R could mediate the effects of TH on cardiac tissue and in
      cardiomyocytes in culture. Wistar rats were subjected to hyperthyroidism with or
      without the AT1R blocker losartan. The TH serum levels, haemodynamic parameters
      and cardiac mass were assessed to confirm the hyperthyroid status. The S100A8,
      MyD88 and nuclear NF-kappaB expression levels were increased in the hearts of the
      hyperthyroid rats, and the losartan treatment attenuated these TH effects. In
      addition, the cultured cardiomyocytes that had been stimulated with losartan
      exhibited blunted S100A8 upregulation and NF-kappaB activation compared with the
      TH-treated cells. Together, our results suggest that AT1R participates in TH
      induced cardiac hypertrophy partly by mediating S100A8, MyD88 and NF-kappaB
      activation via TH. These findings indicate the important crosstalk between TH and
      RAS, highlighting the participation of AT1R in the triggered mechanisms of TH
      that contribute to the cardiac hypertrophy response.

PMID- 29178051
TI  - Behavior Disorders Caused by Perinatal Hypoxia in Juvenile Rats and Their
      Correction with GABA Derivative.
AB  - We studied the effects of acute normobaric hypoxia on postnatal day 2 (model of
      preterm pregnancy) on reflex activity and behavior of juvenile male Wistar rats
      and the possibility of correction of behavioral deficit by administration of GABA
      derivative Salifen after hypoxia. It is shown, that perinatal hypoxia impaired
      righting reflex and forelimb grip strength and increased motor activity in
      juvenile male rats. Administration of Salifen for 14 days in a dose of 15 mg/kg
      improved reflex activity and behavior of rats, which indicates the prospect of
      further study of the therapeutic efficacy of this drug on models of neonatal
      encephalopathy.

PMID- 29178052
TI  - Prospect of Using Cell Product for the Therapy of Skin Defects in Diabetes
      Mellitus.
AB  - The effectiveness of autologous cell product in the therapy of skin burn wounds
      was studied in C57B1/6 male mice against the background of streptozotocin-induced
      diabetes mellitus. In animals with and without modeled diabetes mellitus,
      significant decrease in skin defect area was observed after single administration
      of the cell product (bone marrow multipotent mesenchymal stromal cells,
      fibroblasts or media conditioned by these cells).

PMID- 29178053
TI  - Autosomal Recessive Agammaglobulinemia Due to a Homozygous Mutation in PIK3R1.
AB  - The role of class IA phosphoinositide 3 kinases (PI3Ks) in immune function and
      regulation continues to expand with the identification of greater numbers of
      genetic variants. This case report is the second reported case of a homozygous
      premature stop codon within the PIK3R1 gene leading to autosomal recessive
      agammaglobulinemia. The proband, born to consanguineous parents, presented at 10
      months of age with a history of oropharyngeal petechiae and bleeding from the
      mouth, gums, and tear ducts. Initial investigations revealed thrombocytopenia,
      neutropenia and the absence of B cells. Further genetic testing via a custom next
      generation sequencing panel confirmed the presence of a homozygous mutation in
      PIK3R1, c.901 C>T, a premature stop codon at amino acid position 301. Given their
      many roles in immune regulation, recessive mutations in the PlK3R1 gene should be
      considered in infants presenting with hypogammaglobulinemia or
      agammaglobulinemia, particularly in the setting of parental consanguinity.

PMID- 29178054
TI  - Enhancing Carbohydrate Productivity of Chlorella sp. AE10 in Semi-continuous
      Cultivation and Unraveling the Mechanism by Flow Cytometry.
AB  - Accumulated carbohydrate in microalgae is promising feedstock for bioethanol
      fermentation. Selection of suitable cultivation conditions in semi-continuous
      cultivation is critical to achieve a high carbohydrate productivity. In the
      current study, the effects of macro-nutrient (nitrogen, phosphorus, and sulfur)
      limitations and light intensity were evaluated for the carbohydrate accumulations
      of Chlorella sp. AE10 under 10% CO2 conditions. It was shown that nitrogen
      limitation and high light intensity were effective for improving carbohydrate
      productivity. The average carbohydrate and biomass productivity in semi
      continuous cultivation with 1/4 N medium and 1000 MUmol photons m-2 s-1 was 0.673
      and 0.93 g L-1 day-1, respectively. Sulfur and phosphorus limitations could
      improve the carbohydrate content but they could not enhance the carbohydrate
      productivity. The cell cycle progression and chlorophyll a were investigated
      using flow cytometry (FCM). The results showed that macro-nutrient limitation and
      high light intensity indeed influenced cell cycle progression and led to the
      formation of polyploid cells along with the carbohydrate accumulation in a
      certain range. FCM was rapid and accurate method to investigate the operation
      conditions why 1/4 N, 2 days as a cycle, and high light intensity were optimal
      ones. In addition, the remaining high level of photosynthesis activity was also
      important for achieving a high carbohydrate productivity. Dynamic tracking of
      carbohydrate accumulation is helpful for establishment of a semi-continuous
      cultivation for enhancing carbohydrate productivity in microalgae.

PMID- 29178055
TI  - Solid-State Treatment of Castor Cake Employing the Enzymatic Cocktail Produced
      from Pleurotus djamor Fungi.
AB  - In this work, the enzymatic cocktail produced by Pleurotus djamor fungi extracted
      at pH of 4.8 and 5.3 was employed for castor cake solid-state treatment.
      Proximal, X-ray powder diffraction and scanning electron microscopy analysis of
      the pristine castor cake were carried out. First, Pleurotus djamor stain was
      inoculated in castor cake for the enzymatic production and the enzymatic activity
      was determined. The maximum enzymatic activity was identified at days 14 (65.9
      UI/gss) and 11 (140.3 UI/gss) for the enzymatic cocktail obtained at pH 5.3 and
      4.8, respectively. Then, the enzymatic cocktail obtained at the highest enzymatic
      activity days was employed directly over castor cake. Lignin was degraded
      throughout incubation time achieving a 47 and 45% decrease for the cocktail
      produced at pH 4.8 and 5.3, correspondingly. These results were corroborated by
      the SEM and XRD analysis where a higher porosity and xylan degradation were
      perceived throughout the enzymatic treatment.

PMID- 29178056
TI  - Evaluation of Octyl-beta-D-Glucopyranoside (OGP) for Cytotoxic, Hemolytic,
      Thrombolytic, and Antibacterial Activity.
AB  - The current study indicates that octyl-beta-D-glucopyranoside (OGP) as a
      detergent which has the ability to make the lipid layer stiff. OGP was subjected
      for toxicity studies and in vitro cytotoxicty assays on cancerous HeLa and non
      cancerous myoblasts H9c2 cell lines. Test against aquatic organisms were carried
      out in Artemia salina and LC50 values were calculated. Hemolytic activity tested
      for blood bio-compalibity showed hemolysis rate of 10-16%, followed by
      thrombolytic activity to burst the clots in blood. Also, the samples showed good
      lysis when compared to the standard streptokinase. Furthermore, alpha-amylase
      activity has been carried out to check the inhibition of alpha-amylase by the
      OGP. Finally, antibacterial activity has been tested against four different
      pathogens and their MIC values have been calculated.

PMID- 29178057
TI  - Existence of the passage to the limit of an inviscid fluid.
AB  - In the dynamics of a viscous fluid, the case of vanishing kinematic viscosity is
      actually equivalent to the Reynolds number tending to infinity. Hence, in the
      limit of vanishing viscosity the fluid flow is essentially turbulent. On the
      other hand, the Euler equation, which is conventionally adopted for the
      description of the flow of an inviscid fluid, does not possess proper turbulent
      behaviour. This raises the question of the existence of the passage to the limit
      of an inviscid fluid for real low-viscosity fluids. To address this question, one
      should employ the theory of turbulent boundary layer near an inflexible boundary
      (e.g., rigid wall). On the basis of this theory, one can see how the solutions to
      the Euler equation become relevant for the description of the flow of low
      viscosity fluids, and obtain the small parameter quantifying accuracy of this
      description for real fluids.

PMID- 29178058
TI  - Interaction of soil pH and phosphorus efficacy: Long-term effects of P fertilizer
      and lime applications on wheat, barley, and sugar beet.
AB  - Phosphorus (P), a plant macronutrient, must be adequately supplied for crop
      growth. In Germany, many soils are high in plant-available P; specifically in
      arable farming, P fertilizer application has been reduced or even omitted in the
      last decade. Therefore, it is important to understand how long these soils can
      support sustainable crop production, and what concentrations of soil P are
      required for it. We analyzed a 36-year long-term field experiment regarding the
      effects of different P application and liming rates on plant growth and soil P
      concentrations with a crop rotation of sugar beet, wheat, and barley. Sugar beet
      reacted to low soil P and low soil pH levels more sensitively than wheat, which
      was not significantly affected by the long-term omitted P application. All three
      crop species showed adequate growth at soil P levels lower than the currently
      recommended levels, if low soil pH was optimized by liming. The increase in
      efficacy of soil and fertilizer P by reduced P application rates therefore
      requires the adaptation of the soil pH to a soil type-specific optimal level.

PMID- 29178059
TI  - Functional Land Management: Bridging the Think-Do-Gap using a multi-stakeholder
      science policy interface.
AB  - Functional Land Management (FLM) is proposed as an integrator for sustainability
      policies and assesses the functional capacity of the soil and land to deliver
      primary productivity, water purification and regulation, carbon cycling and
      storage, habitat for biodiversity and recycling of nutrients. This paper presents
      the catchment challenge as a method to bridge the gap between science,
      stakeholders and policy for the effective management of soils to deliver these
      functions. Two challenges were completed by a wide range of stakeholders focused
      around a physical catchment model-(1) to design an optimised catchment based on
      soil function targets, (2) identify gaps to implementation of the proposed
      design. In challenge 1, a high level of consensus between different stakeholders
      emerged on soil and management measures to be implemented to achieve soil
      function targets. Key gaps including knowledge, a mix of market and voluntary
      incentives and mandatory measures were identified in challenge 2.

PMID- 29178061
TI  - A framework of connections between soil and people can help improve
      sustainability of the food system and soil functions.
AB  - Globally soil quality and food security continue to decrease indicating that
      agriculture and the food system need to adapt. Improving connection to the soil
      by knowledge exchange can help achieve this. We propose a framework of three
      types of connections that allow the targeting of appropriate messages to
      different groups of people. Direct connection by, for example, handling soil
      develops soil awareness for management that can be fostered by farmers joining
      groups on soil-focused farming such as organic farming or no-till. Indirect
      connections between soil, food and ecosystem services can inform food choices and
      environmental awareness in the public and can be promoted by, for example,
      gardening, education and art. Temporal connection revealed from past usage of
      soil helps to bring awareness to policy workers of the need for the long-term
      preservation of soil quality for environmental conservation. The understanding of
      indirect and temporal connections can be helped by comparing them with the
      operations of the networks of soil organisms and porosity that sustain soil
      fertility and soil functions.

PMID- 29178062
TI  - AIM2 Inflammasome Is Critical for dsDNA-Induced IL-1beta Secretion in Human
      Dental Pulp Cells.
AB  - The AIM2 inflammasome pathway has been determined to play an important role in
      cellular immune defense against bacterial and viral infections; however, its
      function and regulatory mechanism in human dental pulp cells (HDPCs) during
      pulpitis remains poorly understood. In this study, we explored whether the AIM2
      inflammasome pathway was activated in HDPCs in response to dsDNA and defined its
      role in regulating IL-1beta secretion. We demonstrated that stimulation with IFN
      gamma and cytoplasmic DNA significantly activated the AIM2 inflammasome and
      increased IL-1beta secretion in HDPCs. Moreover, AIM2 overexpression
      significantly up-regulated both cleaved Caspase-1 expression and IL-1beta release
      in HDPCs, while suppression of ASC and Caspase-1 resulted in down-regulation of
      cleaved Caspase-1 and IL-1beta secretion. These results suggest that Caspase-1
      dependent IL-1beta processing and secretion require the AIM2 inflammasome pathway
      in HDPCs and that the AIM2 inflammasome pathway is critical for regulation of the
      dental pulp immune response.

PMID- 29178063
TI  - Evaluation of the performance of three tenodesis techniques for the treatment of
      scapholunate instability: flexion-extension and radial-ulnar deviation.
AB  - Chronic scapholunate ligament (SL) injuries are difficult to treat and can lead
      to wrist dysfunction. Whilst several tendon reconstruction techniques have been
      employed in the management of SL instability, SL gap reappearance after surgery
      has been reported. Using a finite element model and cadaveric study data, we
      investigated the performance of the Corella, scapholunate axis (SLAM) and
      modified Brunelli tenodesis (MBT) techniques. Scapholunate dorsal and volar gap
      and angle were obtained following virtual surgery undertaken using each of the
      three reconstruction methods with the wrist positioned in flexion, extension,
      ulnar deviation and radial deviation, in addition to the ulnar-deviated clenched
      fist and neutral positions. From the study, it was found that, following
      simulated scapholunate interosseous ligament rupture, the Corella technique was
      better able to restore the SL gap and angle close to the intact ligament for all
      wrist positions investigated, followed by SLAM and MBT. The results suggest that
      for the tendon reconstruction techniques, the use of multiple junction points
      between scaphoid and lunate may be of benefit. Graphical abstract The use of
      multiple junction points between scaphoid and lunate may be of benefit for tendon
      reconstruction techniques.

PMID- 29178064
TI  - Deblurring sequential ocular images from multi-spectral imaging (MSI) via mutual
      information.
AB  - Multi-spectral imaging (MSI) produces a sequence of spectral images to capture
      the inner structure of different species, which was recently introduced into
      ocular disease diagnosis. However, the quality of MSI images can be significantly
      degraded by motion blur caused by the inevitable saccades and exposure time
      required for maintaining a sufficiently high signal-to-noise ratio. This
      degradation may confuse an ophthalmologist, reduce the examination quality, or
      defeat various image analysis algorithms. We propose an early work specially on
      deblurring sequential MSI images, which is distinguished from many of the current
      image deblurring techniques by resolving the blur kernel simultaneously for all
      the images in an MSI sequence. It is accomplished by incorporating several a
      priori constraints including the sharpness of the latent clear image, the spatial
      and temporal smoothness of the blur kernel and the similarity between temporally
      neighboring images in MSI sequence. Specifically, we model the similarity between
      MSI images with mutual information considering the different wavelengths used for
      capturing different images in MSI sequence. The optimization of the proposed
      approach is based on a multi-scale framework and stepwise optimization strategy.
      Experimental results from 22 MSI sequences validate that our approach outperforms
      several state-of-the-art techniques in natural image deblurring.

PMID- 29178065
TI  - How Far Can Mitochondrial DNA Drive the Disease?
AB  - Mitochondria are one of the dominant drivers for producing cellular energy to
      meet a large number of biological functions, of which the mitochondrial DNA
      (mtDNA) is the control center of energetic driving force and the dominant driver
      of mitochondrial molecular diversification. mtDNA transcription generates the
      necessary RNAs to regulate the extent and nature of mtRNA post-transcriptional
      modifications and the activity of nucleus-encoded enzymes. With a special focus
      on mtDNA, the current volume aims to overview the biology and structures of
      mtDNA, regulatory roles of mtDNA in lung diseases, or involvement of mtDNA in
      metabolism. We explore the significance of mtDNA sequencing, methylation,
      stability, and mutation in the pathogenesis of the diseases. Molecular mechanisms
      by which mtDNA contribute to the regulation of mitochondrial homeostasis and drug
      resistance are also discussed. We also point out the importance of mitochondrial
      ribosome, single cell biology, and gene editing in the understanding of the
      development of mitochondrial dysfunction in lung disease.

PMID- 29178066
TI  - Mitochondrial DNA in Lung Cancer.
AB  - Mitochondrial DNA (mtDNA) variations are increasingly discovered and expected to
      be potential biomarkers to monitor severity, duration, stage, response to
      therapy, and prognosis in patients with lung cancer. The present article
      illustrates alterations of mtDNA in lung cancer, including alterations of mtDNA
      copy number and sequence mutations, as well as their possible mechanisms for
      carcinogenesis and development of lung cancer. The clear and comprehensive
      relationships between mtDNA variations and lung cancer are to be further
      confirmed to benefit effective strategies for lung cancer diagnosis and therapy.

PMID- 29178067
TI  - Approach, Application, and Bioethics of mtDNA Sequencing in Cancer.
AB  - Mitochondrial DNA (mtDNA) is more vulnerable to mutations and associated with
      many solid tumors. Through mtDNA sequencing, we can find useful information on
      the mutations implicated in diseases and can better define the impact of
      mitochondrial dysfunction on the process of carcinogenesis. In current article,
      we will discuss the current approaches of mtDNA sequencing and the challenges we
      should overcome, their applications in various cancers, and the potential
      bioethics problems we should face in the application of mtDNA sequencing in
      clinical diagnosis and treatment.

PMID- 29178068
TI  - Roles of Mitochondrial DNA Signaling in Immune Responses.
AB  - Mitochondrial DNA (mtDNA) plays an important role in immune responses during the
      evolution. The present chapter systemically describes its role on immune-related
      diseases and its interaction on immune responses. It is important to explore the
      main function and mechanisms of mtDNA in immune responses by which mtDNA
      regulates the signaling pathways of Toll-like receptor 9, autophagy, and STING.
      There are potentials to discover therapeutic targets of mtDNA in immune diseases
      and inflammation. It will be more exciting if the CRISPR-Cas9 method can be
      applied for mtDNA gene editing to cure diseases and provide a novel insight of
      mtDNA in immune responses as well as new therapies.

PMID- 29178069
TI  - Mitochondrial DNA in Telocytes.
AB  - Telocyte (TC) is a new identified interstitial cell type with a small nuclear and
      one or several long and thin prolongations with enlargements on them. They were
      found in many mammals including humans, mouse, rats, dogs, and monkeys and play
      vital roles in many physiological and pathological conditions. The ultrastructure
      of mitochondria was observed in TCs, and the alterations were found in TCs from
      inflammatory ureter tissue. MtDNA is associated with mitochondria normal
      functions and involved in physiological and pathological processes. However,
      mitochondria and mtDNA in TCs were not investigated deeply. This review will
      introduce the origin, distribution, morphology, and functions of TCs and the
      distribution and functions of TC mitochondria in order to improve a better
      understanding of the potential functions of mtDNA in TCs.

PMID- 29178070
TI  - Roles of Mitochondrial DNA in Energy Metabolism.
AB  - Mitochondria are independent double-membrane organelles responsible for energy
      production, specifically by completing oxidative phosphorylation. Mitochondria
      are essential to regulate energy metabolism, signaling pathways, and cell death.
      Mitochondrial DNA (mtDNA) can be altered by metabolic disorders, oxidative
      stress, or inflammation in the progression and development of various diseases.
      In this chapter, we overview the role of mtDNA in energy metabolism and the
      diseases that are associated with mtDNA abnormality, with a special focus on the
      major factors which regulate the mechanism of mtDNA in metabolism.

PMID- 29178071
TI  - The Role of DNA Repair in Maintaining Mitochondrial DNA Stability.
AB  - Mitochondria are vital double-membrane organelles that act as a "powerhouse"
      inside the cell and have essential roles to maintain cellular functions, e.g.,
      ATP production, iron-sulfur synthesis metabolism, and steroid synthesis. An
      important difference with other organelles is that they contain their own
      mitochondrial DNA (mtDNA). Such powerful organelles are also sensitive to both
      endogenous and exogenous factors that can cause lesions to their structural
      components and their mtDNA, resulting in gene mutations and eventually leading to
      diseases. In this review, we will mainly focus on mammalian mitochondrial DNA
      repair pathways that safeguard mitochondrial DNA integrity and several important
      factors involved in the repair process, especially on an essential pathway, base
      excision repair. We eagerly anticipate to explore more methods to treat related
      diseases by constantly groping for these complexes and precise repair mechanisms.

PMID- 29178072
TI  - Is Mitochondrial Cell Fragility a Cell Weakness?
AB  - Mitochondrial dysfunction has historically been linked to the cessation of cell
      function and ageing. Downstream effects such as reduced calcium buffering
      capacity, elevated levels of reactive oxygen species, and alterations in
      adenosine-5'-triphosphate are linked to a wide variety of pathological diseases.
      The importance of the mitochondria has increasingly been highlighted due to its
      potential as a therapeutic target for drug intervention and cell elimination in
      cancer. In addition, due to its origin, drugs targeting bacteria are required to
      be thoroughly tested prior to administration to prevent toxicity for the
      mitochondria. In this chapter, we will discuss a variety of factors that could
      influence mitochondrial dysfunction and highlight potential solutions to these. A
      comprehensive understanding regarding the mechanisms underlying mitochondrial
      dysfunction could aid in developing future therapeutic targets in multiple
      pathologies such as cancer and liver diseases.

PMID- 29178073
TI  - Mitochondrial DNA Methylation and Related Disease.
AB  - Most researchers focused on methylation of genomic DNA, while methylation of
      mitochondrial DNA (mtDNA) is rarely tauched, and there is still controversy about
      the existence of mtDNA methylation. The study of cytosine methylation in mtDNA is
      limited. The mtDNA was recently found to exist CpG hypomethylation, and more
      studies provided evidence that mtDNA methylation plays an important role in
      mitochondrial gene regulation. In present review, we will overview recent studies
      of mitochondrial DNA methylation and potential influencing factors in diseases
      that are involved in mtDNA methylation. Thus, the further studies on mtDNA
      methylation will provide more evidence to explain the mechanism of mtDNA
      methylation and an advantageous approach for human clinical diagnosis and
      prevention.

PMID- 29178074
TI  - Beyond Deubiquitylation: USP30-Mediated Regulation of Mitochondrial Homeostasis.
AB  - Mutations or sequence aberrations in the Parkin gene are among the most common
      causes of autosomal recessive Parkinson's disorder (PD). Parkin, a cytoplasmic E3
      ubiquitin ligase, is involved in mitochondrial quality control pathways,
      including mitochondrial fission and mitophagy by autophagy-related genes. Parkin
      mediates the covalent addition of ubiquitin (Ub) chains to Lys 6, Lys 11, and Lys
      63 on diverse mitochondrial-related target proteins. USP30, a mitochondrial
      deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination
      of ubiquitylated forms of mitofusins, such as Mfn1 and Mfn2. USP30 preferentially
      mediates the removal of Ub chains from Lys 6 and Lys 11 on mitochondria-derived
      proteins. USP30 mediates the removal of the ubiquitin chains added by Parkin. It
      was demonstrated that overexpression of USP30 triggers the mitochondrial dynamic
      signaling toward elevated fusion and reduced fission and halts mitochondrial
      clearance via mitophagy. Although mounting lines of evidences reveal the pivotal
      role of Parkin in mitochondrial quality control pathways, the crucial role of
      deubiquitinases including the USP30 deubiquitinase is emerging. Herein, we review
      briefly the role of USP30 in the dynamic networks of mitochondrial quality
      control and its physiological implications.

PMID- 29178075
TI  - Metabolic Regulation in Mitochondria and Drug Resistance.
AB  - Mitochondria are generally considered as a powerhouse in a cell where the
      majority of the cellular ATP and metabolite productions occur. Metabolic rewiring
      and reprogramming may be initiated and regulated by mitochondrial enzymes. The
      hypothesis that cellular metabolic rewiring and reprogramming processes may occur
      as cellular microenvironment is disturbed, resulting in alteration of cell
      phenotype, such as cancer cells resistant to therapeutics seems to be now
      acceptable. Cancer metabolic reprogramming regulated by mitochondrial enzymes is
      now one of the hallmarks of cancer. This chapter provides an overview of cancer
      metabolism and summarizes progress made in mitochondria-mediated metabolic
      regulation in cancer drug resistance.

PMID- 29178076
TI  - Mitochondrial Lon Protease and Cancer.
AB  - ATP-dependent Lon protease of mitochondrial matrix is encoded by nuclear DNA and
      highly evolutionarily conserved throughout all organisms, which is involved in
      the quality control of proteins by selective degradation of misfolded, oxidized,
      and short-lived regulatory proteins within mitochondrial matrix, maintenance of
      mitochondrial genome (mtDNA), and folding of mitochondria proteins. Various
      stimuli such as hypoxia and oxidative and ER stress lead to upregulation of Lon
      expression. Inhibition of protease activity or downregulation of Lon promotes
      cancer cell death and enhances sensitivity of cancer cells to anticancer drugs
      through metabolic reprogramming, thus reducing the viability of cancer cell in
      tumor microenvironment and epithelial to mesenchymal transition (EMT). Moreover,
      mitochondrial ATP-dependent Lon protease may serve as a potential biomarker for
      cancer diagnosis and novel target for the development of anticancer drugs and for
      predicting of the efficiency and effectiveness of chemotherapy of a variety of
      cancers.

PMID- 29178077
TI  - Regulatory Roles of Mitochondrial Ribosome in Lung Diseases and Single Cell
      Biology.
AB  - The mitochondria have the most vital processes in eukaryotic cells to produce ATP
      composed of polypeptides that are produced via ribosomes, as oxidative
      phosphorylation. Initially, studies regarding human mitochondrial ribosomes were
      performed in the model system, bovine mitochondrial ribosome, to investigate how
      ribosomes are biosynthesized and evolved as well as what their structure and
      function are. Advances in X-ray crystallography have led to dramatic progresses
      in structural studies of the ribosome. In recent years, there has been a growing
      interest in the properties of the mitochondrial ribosome. Although one of its
      main functions is the production of ATP, it was also linked to multiple diseases.
      A key area that remains unexplored and requires investigation and exploration is
      how mitochondrial ribosomal RNA (mt-rRNA) variations can affect the mitochondrial
      ribosomes in developing disease. This review summarizes the structure, elements,
      functions, and regulatory roles in associated diseases. With the continuous
      development of technology, studies on the mechanism of mitochondrial ribosome
      related diseases are crucial, in order to identify methods of prevention and
      treatment of these disorders.

PMID- 29178078
TI  - Epithelial Mitochondrial Dysfunction in Lung Disease.
AB  - Since the twentieth century, scientists have studied the functions and mechanisms
      of the mitochondria. The mitochondrion plays many important roles in cell
      functioning and contributes to apoptosis, embryonic and tissue development,
      aging, etc. Consequently, mitochondrial dysfunction often has a direct impact on
      health such as aging, tumorigenesis, lung injury and COPD, etc. Recent evidence
      indicates that the mitochondria could also be a crucial contributor to immunity
      with functions such as biogenesis, fusion, and fission impacting various areas in
      initializing immunity. In this review, we will describe both the structure and
      various functions of the mitochondria with an emphasis on functions such ATP
      production which is crucial for a multitude of processes such as apoptosis,
      biosynthesis of Fe/S clusters, steroid synthesis, and, more fundamentally, cell
      survival. In addition, this review aims to investigate the relationship of
      epithelial mitochondria and lung disease. Cigarette smoke is known to induce
      structural and functional mutations in airway epithelial mitochondria often
      acting as an indicator for diseases such as COPD. Further evidence to support
      this speculation is the presence of reactive oxygen species (ROS) within
      cigarette smoke which is a factor in the development of COPD.

PMID- 29178079
TI  - Significance of Mitochondria DNA Mutations in Diseases.
AB  - Mitochondria are essential double-membraned cytoplasmic organelles to support
      aerobic respiration and produce cellular energy by oxidative phosphorylation
      (OXPHOS). Mitochondrial functions are controlled by mitochondrial (mtDNA) and
      nuclear genomes (nDNA). Mutations of mtDNA result in mitochondrial dysfunction
      and multisystem diseases through compromising OXPHOS function directly by a point
      mutation or a large-scale mtDNA rearrangement. One or more of OXPHOS complexes
      are impaired and dysfunctional to affect tissues with high energy demands. mtDNA
      is more susceptible to oxidative damage and has more mutations than nDNA. Unlike
      diploid nDNA, mtDNA is a multi-copy genome transmitted and maternally inherited
      through oocyte. The multi-copy nature of mtDNA easily causes the heteroplasmy as
      a unique aspect of mtDNA, making mitochondrial diseases more complex and
      heterogeneous. mtDNA-associated mitochondrial dysfunction plays the important
      role in the development of multisystemic primary mitochondrial disease,
      neurodegeneration, and cancer. The present article overviews the occurrence of
      mtDNA mutation, interactions with other factors, and molecular mechanisms of
      mtDNA-associated diseases.

PMID- 29178080
TI  - Statistical description of the denatured structure of a single protein,
      staphylococcal nuclease, by FRET analysis.
AB  - Structural characterization of fully unfolded proteins is essential for
      understanding not only protein-folding mechanisms, but also the structures of
      intrinsically disordered proteins. Because an unfolded protein can assume all
      possible conformations, statistical descriptions of its structure are most
      appropriate. For this purpose, we applied Forster resonance energy transfer
      (FRET) analysis to fully unfolded staphylococcal nuclease. Artificial amino acids
      labeled with a FRET donor or acceptor were introduced by an amber codon and a
      four-base codon respectively. Eight double-labeled proteins were prepared,
      purified, and subjected to FRET analysis in 6 M urea. The observed behavior could
      be explained by a power law, R = alphaN0.44, where R, and N are the distance and
      the number of residues between donor and acceptor, and alpha is a coefficient.
      The index was smaller than the value expected for an excluded-volume random coil,
      0.588, indicating that the fully unfolded proteins were more compact than
      polypeptides in good solvent. The FRET efficiency in the native state did not
      necessarily correlate to the distance obtained from crystal structure, suggesting
      that other factors such as the orientation factor made a substantial contribution
      to FRET.

PMID- 29178081
TI  - Stimuli-responsive nanocarriers for intracellular delivery.
AB  - The emergence of different nanoparticles (NPs) has made a significant revolution
      in the field of medicine. Different NPs in the form of metallic NPs, dendrimers,
      polymeric NPs, carbon quantum dots and liposomes have been functionalized and
      used as platforms for intracellular delivery of biomolecules, drugs, imaging
      agents and nucleic acids. These NPs are designed to improve the pharmacokinetic
      properties of the drug, improve their bioavailability and successfully surpass
      physiological or pathological obstacles in the biological system so that
      therapeutic efficacy is achieved. In this review I present some of the current
      approaches used in intracellular delivery systems, with a focus on various
      stimuli-responsive nanocarriers, including cell-penetrating peptides, to
      highlight their various biomedical applications.

PMID- 29178082
TI  - Conversion of microbial rhodopsins: insights into functionally essential elements
      and rational protein engineering.
AB  - Technological progress has enabled the successful application of functional
      conversion to a variety of biological molecules, such as nucleotides and
      proteins. Such studies have revealed the functionally essential elements of these
      engineered molecules, which are difficult to characterize at the level of an
      individual molecule. The functional conversion of biological molecules has also
      provided a strategy for their rational and atomistic design. The engineered
      molecules can be used in studies to improve our understanding of their biological
      functions and to develop protein-based tools. In this review, we introduce the
      functional conversion of membrane-embedded photoreceptive retinylidene proteins
      (also called rhodopsins) and discuss these proteins mainly on the basis of
      results obtained from our own studies. This information provides insights into
      the molecular mechanism of light-induced protein functions and their use in
      optogenetics, a technology which involves the use of light to control biological
      activities.

PMID- 29178084
TI  - Comment on: "Health Benefits of Light-Intensity Physical Activity: A Systematic
      Review of Accelerometer Data of the National Health and Nutrition Examination
      Survey (NHANES)".

PMID- 29178083
TI  - Author's Reply to Lopez: Comment on "Health Benefits of Light-Intensity Physical
      Activity: A Systematic Review of Accelerometer Data of the National Health and
      Nutrition Examination Survey (NHANES)".

PMID- 29178085
TI  - Author's Reply to Nunes et al.: Comment on: "Comparison of Periodized and Non
      Periodized Resistance Training on Maximal Strength: A Meta-Analysis".

PMID- 29178086
TI  - Comment on: "Comparison of Periodized and Non-Periodized Resistance Training on
      Maximal Strength: A Meta-Analysis".

PMID- 29178087
TI  - [Retrospect and prospect: brief history and current status of gastrointestinal
      surgery in Guangdong Province, China].
AB  - The First Affiliated Hospital of Sun Yat-sen University has made many lasting
      contributions to gastrointestinal surgery in Guangdong Province and even in
      China. The Department of Gastrointestinal Surgery was established at the First
      Affiliated Hospital of Sun Yat-sen Medical College in 1965, which opened the
      prelude to the development of gastrointestinal surgery in Guangdong. This article
      summarizes the evolution of gastrointestinal surgery and highlights the
      milestones specific to the field of gastrointestinal surgery in Guangdong
      Province, China. Main features and trends of gastrointestinal surgery in
      Guangdong Province are analyzed as well.

PMID- 29178088
TI  - [Education and training for laparoscopic gastrointestinal surgery: our 10 years'
      experience in Nanfang Hospital].
AB  - The laparoscopic surgery for gastrointestinal cancer developed slowly and was at
      a crossroad of choice at the beginning of the 21st century. However, the team of
      laparoscopic surgery in Nanfang Hospital was keenly conscious that minimally
      invasive surgery (MIS) would bring new era to the treatment of gastrointestinal
      cancer. Therefore, our team went into the exploration of laparoscopic surgery for
      gastrointestinal cancer: (1) researching a series of anatomical theories for MIS;
      (2) lucubrating the applicable pattern of fascia and mesentery under laparoscopic
      view; (3) finding out the precise anatomical landmarks and surgical layers; (4)
      optimizing the operative strategy. Fortunately, we proposed a safe and simplified
      strategy of laparoscopic gastrointestinal cancer surgery for Chinese patients
      with locally advanced stage. Gradually, this strategy was widely adopted by most
      colleagues in this field. Meanwhile, our team realized the necessity and urgency
      of education and training for primary care physicians, thus we designed courses
      based on different laparoscopic levels of the trainees. Also we actively
      developed the teaching model suitable for the presentation of visual surgery, by
      taking advantages of mobile network and glasses-free 3D, to break through the
      limit of time and space in teaching and learning. Besides, we used the internet
      to create an education system of real-time, opening, practical and efficient
      academic communication platform, so that more surgeons across the country would
      be able to synchronize and interact with the experts more instantly and
      efficiently. All the way, our team hammered at optimizing laparoscopic surgery
      procedures, along with further perfecting and standardizing training and
      education system. This article intends to review, summarize and share our
      experiences in laparoscopic training and education for gastrointestinal surgery,
      also to remind ourselves of staying true and carry on in this field.

PMID- 29178089
TI  - [Current status of hereditary gastrointestinal neoplasms].
AB  - Gastric cancer and colorectal cancer are two common malignant tumors in digestive
      tract. 1% to 3% of gastric cancer and 5% to 15% of colorectal cancer are
      definitely hereditary cancer caused by germline gene mutation. Hereditary gastric
      cancer includes hereditary diffuse gastric cancer(HDGC) and hereditary intestinal
      gastric cancer (HIGC). CDH1 gene mutation is the main reason to cause HDGC, so
      the first degree and the second degree family members of HDGC patients are
      recommended to receive CDH1 mutation detection, endoscopic examination every year
      and undergo preventive total gastrectomy. Hereditary colorectal cancer includes
      hereditary nonpolyposis colorectal cancer (HNPCC, or Lynch syndrome) and familial
      adenomatous polyposis (FAP). Germline MMR gene mutation detection is the golden
      standard of the diagnosis of Lynch syndrome. Family members of Lynch syndrome
      patients are recommended to receive endoscopic examination every year and undergo
      standard cancer radical operation or total colorectal resection based on
      individual conditions. FAP is caused by APC gene mutation, so FAP patients are
      recommended to receive endoscopic examination once or twice every year through
      their lifetime, while a lot of adenoma occur, resection should be considered. The
      promotion key of hereditary gastrointestinal neoplasms research is to follow the
      standard diagnosis and treatment guideline for hereditary gastrointestinal
      neoplasms and build the clinical and gene information bank of hereditary
      gastrointestinal neoplasms. The second generation sequencing technique provides
      favorable research stools in elucidating pathogenesis mechanism of hereditary
      gastrointestinal neoplasms.

PMID- 29178090
TI  - [Treatment of primary gastric lymphoma].
AB  - Stomach is the most common location of lymphoma in digestive tract, accounting
      for 50%-60% of gastrointestinal lymphomas. The most common histological types are
      low malignant mucosa-associated lymphoid tissue (MALT) lymphoma from non-Hodgkin
      lymphoma (NHL) and diffuse large B-cell and marginal zone B-cell lymphoma (DLBCL)
      from NHL. Chronic gastritis secondary to Helicobacter pylori(HP) infection has
      been considered a major predisposing factor for MALT lymphoma. At present, the
      most widely accepted initial therapy for localized disease is aimed at the
      eradication of HP using regimens combining antibiotics and proton-pump
      inhibitors. The irradiation has become the therapy of choice for patients with
      early stage MALT lymphoma without HP infection or with persistent lymphoma
      following antibiotic therapy. In all the patients with advanced disease,
      treatment options include chemotherapy and the use of monoclonal antibodies.
      Treatment of DLBCL in stomach is based on aggressive poly-chemotherapy that is
      usually combined with rituximab. The same guidelines followed for nodal
      aggressive lymphoma can also be applied to gastric lymphoma with aggressive
      histology as DLBCL. For localized stages (stages I( and II(), these guidelines
      suggest front-line therapy with 3 to 4 cycles of standard R-CHOP (rituximab,
      cyclophosphamide, doxorubicin, vincristine and prednisone) followed by
      radiotherapy. Advanced stage patients (stage IIII() usually undergo only 6 to 8
      cycles of R-CHOP in order to obtain a complete remission rate. Nowadays surgery
      is limited to rare cases and radiotherapy combined or not with chemotherapy
      represents an effective therapeutic option ensuring long-term, organ-salvage
      benefits mainly in aggressive histological types.

PMID- 29178091
TI  - [Surgical treatment of chronic radiation enteropathy].
AB  - Chronic radiation enteropathy(CRE) represents a latent intestinal injury
      resulting from abdominal-pelvic radiotherapy. Severe complications like
      refractory bleeding, intestinal obstruction, perforation and fistula may occur
      during CRE progression. Surgical treatment is the most effective way to handle
      these complications. Since radiotherapy has become an important and common way to
      relieve or even cure many malignant tumors, the incidence of severe complications
      of CRE is likely to rise. Thus the value of surgical treatment in managing severe
      complications of CRE should gain more attention. Through the literature review
      combined with our clinical experience, this paper analyzes the preoperative
      management and surgical treatment of five long-term complications of CRE,
      including obstruction, enteric fistula, rectovaginal fistula, perforation and
      bleeding. Also we propose that when managing patients with severe complications
      of CRE, clinicians should carefully master the surgical indications, consummate
      perioperative management, design personal surgical plan according to patient's
      condition and make improving the quality of life of patients the ultimate purpose
      of surgical treatment for CRE while assuring its safety.

PMID- 29178092
TI  - [Updates of 2017 ESMO guideline for rectal cancer].
AB  - Compared with the 2013 version, the basic strategies of diagnosis and treatment
      for rectal cancer in the 2017 version guideline remain the same. These strategies
      include accurate local staging approaches which combines digital rectal
      examination, endorectal ultrasound (ERUS), and high resolution pelvic MRI, and
      local recurrence risk grading system which combines tumor location/distance, T
      staging, N staging, EMVI (extramural vascular invasion) and MRF(mesorectal
      fascia). And personalized therapeutic principle based on the above local risk
      grading. Main updates for the 2017 version are as following: (1) x-ray chest film
      is placed by CT scan for baseline staging, and PET-CT is recommended for patients
      with extensive EMVI on MRI imaging to exclude further distant metastasis. (2) For
      local recurrence risk grading, there is one new grade clarified as "intermediate
      group" added to the 2017 version, which includes patients with very low cT3a/b,
      levators clear, MRF clear or cT3a/b in mid or high rectum, cN1-2, no EMVI. These
      patients were classified as "bad group" in the old 2013 version. Accordingly,
      treatment recommendations for this group changed from preoperative CRT or SCPRT
      followed by TME surgery to TME surgery alone if good quality of TME assured.
      Another important notice made in the new guideline is to emphasize the critical
      role of surgical quality of TME, which should be assessed by a pathologist with
      help of photography of fresh specimen. In summary, 2017 version of ESMO guideline
      for rectal cancer is a more personalized and clinically relevant guideline.

PMID- 29178093
TI  - [Role of nutrition support in the enhanced recovery after surgery for
      gastrointestinal surgery patients].
AB  - Nutrition support therapy can improve the general condition of the patient and is
      one of the main factors to ensure the success of the operation. Enhanced recovery
      after surgery (ERAS) improves the recovery following gastrointestinal surgery by
      reducing postoperative stress response. The application of nutrition support in
      ERAS includes nutrition risk assessment before surgery and preoperative nutrition
      treatment for malnutrition. The time to fasting and clear liquid was shortened to
      6 h and 2 h before anesthesia induction. Early postoperative recovery of oral
      feeding can improve the patient's clinical outcome. The application of ERAS
      enables the development and improvement of clinical nutrition concepts, and
      deepens the role of nutrition support therapy, which is conducive to the recovery
      of patients.

PMID- 29178094
TI  - [Status quo of colorectal cancer screening in Guangzhou community].
AB  - The incidence of colorectal cancer (CRC) in China is gradually increasing as a
      result of the economic development and dietary change. Since it usually takes a
      long time for precancerous lesions (e.g. adenoma) to develop into cancer, proper
      cancer screening is useful to discover and to remove these early lesions, while
      the patients can achieve long-term survival. Hence, developing a well-organized
      cancer screening system is necessary for the early detection and intervention of
      potential CRC. Sun Yat-sen University Cancer Center (SYSUCC) has been developing
      a community-based cancer screening program, using questionnaires and fecal occult
      blood test to identify the residents with high risks of CRC. These people will be
      further subjected to colonoscopy and biopsy for the suspected lesions. Among the
      1 030 participants in Guangzhou Yuexiu District who received colonoscopy at
      SYSUCC from January to November in 2015, polyps, inflammation or tumors were
      found in 361 (35.0%) patients, in whom 13 were colorectal cancers (1.3%), 327
      were polyps (31.7%), 239 were adenoma (23.2%), and 140 were prophase
      adenoma(13.6%). Besides, no significant difference of CRC detection rate between
      male and female was found (P>0.05), while the detection rate of polyps and
      prophase adenoma was higher in male than that in female, which also increased
      significantly with age (P<0.01). We envision such systematic cancer screening
      extremely useful to enhance the understanding of cancer screening in the public
      and eventually to realize the early detection and treatment of cancer.

PMID- 29178095
TI  - [Efficacy analysis of proximally extended resection for locally advanced rectal
      cancer after neoadjuvant chemoradiotherapy].
AB  - OBJECTIVE: To evaluate the short-term outcomes and perioperative safety of
      proximally extended resection for locally advanced rectal cancer after
      neoadjuvant chemoradiotherapy. METHODS: From colorectal cancer database in The
      Sixth Affiliated Hospital of Sun Yat-sen University, a cohort of patients who
      underwent neoadjuvant chemoradiotherapy(1.8-2.0 Gy per day, 25-28 fractions,
      concurrent fluorouracil-based chemotherapy) followed by curative sphincter
      preserving surgery for locally advanced rectal cancer between May 2016 and June
      2017 were retrospectively identified. Exclusion criteria were synchronous colon
      cancer, intraoperatively confirmed distal metastasis, multiple visceral
      resection, and emergency operation. Thirty-one patients underwent proximal
      extended resection and two were excluded for incomplete extended resection, then
      29 patients were enrolled as the extended group. Using propensity scores matching
      with 1/1 ration, 29 locally advanced rectal cancer patients who underwent
      conventional resection after neoadjuvant chemoradiotherapy at the same time were
      matched as the conventional group. Clinical data of two groups were analyzed, and
      the baseline characteristics and short-term outcomes were compared using the t
      test, chi2 test, or Mann-Whitney U test. RESULTS: Two groups were well balanced
      with respect to the baseline characteristics after propensity score matching. As
      compared with conventional group, patients in extended group had longer surgical
      specimen [(18.8+/-5.1) cm vs.(11.6+/-3.4) cm, t=6.314, P=0.000] and longer
      proximal resection margin [(14.8+/-5.5) cm vs.(8.2+/-3.0) cm, t=5.725, P=0.000],
      but also had longer total operating time [(322.4+/-100.7) min vs.(254.6+/-70.3)
      min, t=2.975, P=0.004] and more intraoperative blood loss [100(225) ml vs.
      100(50) ml, Z=-2.403, P=0.016]. No significant differences were observed in the
      length of distal resection margin, ratio of positive resection margin, number of
      retrieved lymph node, time of analgesic use, time of draining tube use, time to
      first flatus, time to first oral diet, and postoperative hospital stay. During
      the perioperative period of 30 days, the morbidity of complication in extended
      group and conventional group was 17.2%(5/29) and 34.5% (10/29), respectively
      (P=0.134). CONCLUSION: Proximally extended resection is a radical and safe
      surgical alternative for locally advanced rectal cancer after neoadjuvant
      chemoradiotherapy, which can potentially reduce the risk of anastomosis
      complication.

PMID- 29178096
TI  - [Risk factors and outcomes of postoperative delirium in colorectal cancer
      patients over 60 years].
AB  - OBJECTIVE: To determine the incidence, risk factors and clinical outcomes of
      postoperative delirium in colorectal cancer patients over 60 years. METHODS:
      Consecutive 382 patients older than 60 years undergoing colorectal cancer surgery
      at Shenzhen Second People's Hospital from June 2013 to June 2016 were recruited
      prospectively in this study. These patients were evaluated daily after surgery
      for 7 days by confusion assessment method. Clinical outcomes were compared
      between patients with and without postoperative delirium, including postoperative
      complications, length of hospital stay, and mortality within 30 days. Logistic
      regression analysis was used to identify independent predictors of postoperative
      delirium. RESULTS: There were 230 male and 152 female patients with median age of
      67(range 60 to 92) years. Among them, 213 had colon cancer and 169 had rectal
      cancer. Postoperative delirium developed in 46(12.0%) patients, and most
      deliriums (78.3%) were diagnosed within 3 days after surgery. Patients with
      postoperative delirium had more complications [30.4%(14/46) vs. 17.3%(58/336),
      P=0.032], higher mortality [6.5%(3/46) vs. 1.8%(6/336), P=0.047], and longer
      postoperative hospital stay (median 14 days vs. 9 days, P=0.008). Univariate
      analysis revealed that advanced age, male, higher Charlson comorbidity index,
      higher American Society of Anesthesiologists Classification, lower preoperative
      blood albumin concentration, history of psychiatric disease, history of
      cerebrovascular disease, alcohol abuse, emergent operation, and perioperative
      blood transfusion were significantly related to the development of postoperative
      delirium. Logistic regression analysis identified that advanced age (OR=1.06,
      95%CI: 1.01 to 1.13), history of psychiatric disease (OR=10.89, 95%CI: 2.73 to
      41.59) and perioperative blood transfusion (OR=2.37, 95%CI: 1.11 to 7.32) were
      independent risk factors of postoperative delirium. CONCLUSIONS: Postoperative
      delirium is relatively common in elderly patients over 60 years undergoing
      colorectal cancer surgery. The high morbidity of postoperative complication and
      mortality associated with postoperative delirium warrant implementation of
      preoperative risk assessment and postoperative screening protocol for
      postoperative delirium. Comprehensively preventive strategies should be carried
      out for high-risk patients, e.g. advanced age, history of psychiatric disease,
      and perioperative blood transfusion.

PMID- 29178097
TI  - [Association of early diarrhea and fecal volume with anastomotic leakage after
      low anterior resection of rectal cancer].
AB  - OBJECTIVE: To evaluate the association of early diarrhea and fecal volume with
      anastomotic leakage after low anterior resection (LAR) of rectal cancer. METHODS:
      Clinical data of 541 patients with rectal cancer undergoing LAR at The Affiliated
      Hospital of Guangdong Medical College between January 2007 and January 2017 were
      analyzed retrospectively. Early postoperative diarrhea was defined as at least
      one occurrence of more than 50 ml watery stool or at least four times defecation
      per day within 7 days after surgery. The volume of fecal discharge from the
      transanal drain was measured at daily intervals for 3 days after surgery.
      Association of early diarrhea and anastomotic leakage was analyzed using logistic
      regression model. The accuracy of fecal volume in predicting anastomotic leakage
      was evaluated using receiver operating characteristics (ROC) curve. RESULTS:
      There were 319 males and 222 females with mean age of 59.3 years. Early
      postoperative diarrhea occurred in 99(18.3%) patients, and 41(7.6%) patients
      developed anastomotic leakage. The incidence of anastomodc leakage in patients
      with early diarrhea was significantly higher as compared to those without early
      diarrhea (15.2% vs. 5.9%, P=0.000). Multivariate analysis revealed that early
      diarrhea (OR=33.940, 95%CI: 8.423 to 89.240) and the distance between the tumor
      and the anal verge less than 7 cm (OR=13.085, 95%CI: 2.117 to 44.556) were
      independent risk factors for anastomotic leakage, while the presence of a
      transanal tube was an independent protective factor (OR=0.474, 95%CI: 0.122 to
      0.881). The total fecal volume for 3 days after surgery was calculated in 162
      patients with a transanal tube. The median fecal volume was 210 (100 to 4360) ml
      and 60 (0 to 480) ml in patients with and without anastomotic leakage
      respectively(P=0.000). ROC curve showed that the cut-off value of fecal volume
      for anastomotic leakage was 110 ml and the area under the curve was 0.824 with a
      high sensitivity of 85.7% and specificity of 81.3%. CONCLUSIONS: Early
      postoperative diarrhea after LAR procedure of rectal cancer may be an early
      predictor of anastomotic leakage, and fecal volume for 3 days after surgery >=110
      ml can accurately predict anastomotic leakage. Active prevention and management
      of early postoperative diarrhea may reduce the risk of anastomotic leakage.

PMID- 29178098
TI  - [Evaluation of three-dimensional CT reconstruction on the anatomic variation of
      inferior mesenteric artery and left colic artery].
AB  - OBJECTIVE: To demonstrate the clinical applicability of three-dimensional CT
      angiography by evaluating the anatomic features and variation of inferior
      mesenteric artery(IMA) and left colic artery(LCA) in order to provide reference
      to vessel ligation strategy in laparoscopic rectal cancer surgery. METHODS:
      Clinical and image data of 123 patients receiving abdominal multislice CT at The
      Sixth Affiliated Hospital from 2014 to 2015 were retrospectively analyzed. The
      images were 3D-reconstructed with computer 3D CT angiography and arterial
      enhancement phase images were chosen for analysis. Linear distances from IMA root
      to abdominal aortic bifurcation and from LCA at IMA root level to IMA root were
      measured. Branch types of IMA, coursing pattern of LCA, and association between
      LCA and inferior mesenteric vein (IMV) site were summarized. RESULTS: Of 123
      cases, 80 were males and 43 were females, mean age was (46.8+/-16.6) years, body
      weight was (57.7+/-10.4) kg, and BMI was (21.3+/-3.6) kg/m2. The average distance
      from IMA root to abdominal aortic bifurcation was (42.5+/-7.9) mm, and this
      distance was closely associated with body weight (OR=4.771, 95%CI: 1.398 to
      16.283, P=0.013). Longer distance tended to appear in the heavier patients. LCA
      and sigmoid artery (SA) originating from same single IMA was found in 61(49.6%)
      cases; LCA and SA forking at same point in 35(28.5%) cases; LCA and SA coursing
      together and forking afterwards in 24(19.5%) cases, and LCA disappearing in
      3(2.4%) cases. In 71(57.7%) patients, LCA ascended medial to the lateral border
      of left kidney, while in 16(13.0%) patients, LCA arranged below the inferior
      border of left kidney. When the LCA site was higher and the distance from LCA to
      IMA root was closer [distance from LCA to IMA root level was (24.2+/-9.9) mm,
      (30.0+/-15.2) mm and (66.6+/-12.3) mm, F=83.2, P<0.001]. At the level of IMA
      root, LCA located medial to IMV in 21(17.1%) cases, located just lateral to IMV
      in 54(43.9%) cases, and located lateral and ascended far away from IMV in
      48(39.0%) cases. CONCLUSION: 3D-CT angiography is non-invasive, efficient and
      accurate in evaluating coursing features and variation of IMA and its branches,
      which can provide important reference to the surgeons, promising laparoscopic
      surgery smooth and safe.

PMID- 29178099
TI  - [Analysis of risk factors on pulmonary infection after D2 lymphadenectomy
      gastrectomy for gastric cancer].
AB  - OBJECTIVE: To explore the risk factors of pulmonary infection after D2 radical
      gastrectomy of gastric cancer in order to guide clinical measures to reduce the
      incidence of pulmonary infection. METHODS: Clinical data of 371 patients
      undergoing D2 radical gastrectomy at Division 2 of Gastrointestinal Cancer Center
      from October 2014 to October 2016 were collected for retrospective cohort study.
      Associated risk factors of pulmonary infection after D2 radical gastrectomy of
      gastric cancer were analyzed. Diagnosis criteria of pulmonary infection:
      occurrence of new pulmonary rales; new infiltrative change or consolidation in
      chest by imaging examination; with at least one of the following: temperature
      >=38.5centi-degree, emergence of new purulent sputum or sputum character change,
      isolated pathogens from bronchial brush biopsy or tracheal secretion culture.
      RESULTS: Of 371 patients, 265 were males and 106 were females. The average age
      was 59.1(22-80) years old. There were 38(10.2%) cases of pulmonary infection
      after radical resection of gastric cancer. Univariate analysis showed that
      smoking history, intra-operative blood loss >=200 ml, total gastrectomy, and
      gastric intubation >=6 d were associated with pulmonary infection after D2
      radical gastrectomy (all P<0.05). Six cases quitted smoking 2 weeks before
      operation with pulmonary infection incidence of 8.1%(6/74), and 16 patients did
      not quit smoking 2 weeks before operation with pulmonary infection incidence of
      21.1%(16/76), and the difference was statistically significant (chi2=4.0387,
      P=0.0445). Multivariate Logistic regression analysis showed that postoperative
      gastric intubation >=6 d (OR=4.335, 95%CI: 1.088 to 4.586, P=0.05), smoking
      history (OR=3.469, 95%CI: 1.056 to 5.252, P=0.043) and intra-operative blood loss
      >=200 ml (OR=3.931, 95%CI: 1.350 to 10.574, P=0.013) were independent risk
      factors of pulmonary infection after D2 radical gastrectomy of gastric cancer.
      CONCLUSION: For gastric cancer patients undergoing D2 radical gastrtectomy with
      smoking history, greater blood loss during operation and postoperative gastric
      intubation >=6 d, surgeons must pay attention to the prevention of postoperative
      pulmonary infection.

PMID- 29178100
TI  - [Lymph node metastasis regularity and risk factors in 768 cardiac carcinoma
      patients].
AB  - OBJECTIVE: To investigate the regularity of lymph node metastasis in cardiac
      carcinoma and its risk factors. METHOD: Complete clinicopathological data of 768
      cardiac carcinoma patients undergoing radical resection and lymph node dissection
      were collected. A retrospective cohort study was performed to analyze the
      distribution of lymph node metastasis (lymph node metastasis rate=number of
      patients with lymph node metastasis/number of patients with lymph node
      dissection; lymph node metastasis frequency=number of metastatic lymph
      node/number of total resected lymph node) and the influence of
      clinicopathological factors on lymph node metastasis. RESULTS: Of the 768
      patients, 599 were male and 169 were female, with mean age of 61(28 to 85) years.
      According to gastric cancer staging criteria from the American Joint Cancer
      Association (AJCC) 7th edition in 2010, there was 256 cases in N0 stage, 171
      cases in N1 stage, 181 cases in N2 stage, 160 cases in N3 phase; 18 cases in T1
      stage, 30 cases in T2 stage, 9 cases in T3 stage, 711 cases in T4 stage. Borrmann
      type I( was found in 61 cases, type II( in 306 cases, type III( in 358 cases,
      type IIII( in 43 cases. The histological type was adenocarcinoma in 738 cases and
      signet ring cell carcinoma in 30 cases. A total of 9 183 lymph nodes were
      resected during operation for 768 patients with mean 12(0 to 57) nodes per case,
      while 510 patients were found to have 2 889 metastatic nodes; the lymph node
      metastasis rate was 66.4%(510/768), and lymph node metastasis frequency was
      31.5%(2 889/9 183). Besides, 483 patients were found to have 2 759 metastatic
      lymph nodes and 8 246 resected lymph nodes in abdominal cavity with lymph node
      metastasis rate of 62.9%(483/768) and lymph node metastasis frequency of 33.5% (2
      759/8 246); 57 patients were found to have 130 metastatic lymph nodes and 937
      resected lymph nodes in thoracic cavity with lymph node metastasis rate of
      7.4%(57/768) and lymph node metastasis frequency of 13.9%(130/937). Stations with
      the higher lymph node metastasis rate included paracardiac (left cardia: 38.8%,
      right cardia: 39.9%), lesser curvature of stomach(41.9%), left gastric artery
      (46%) and posterior pancreatic (38.5%). A total of 361 patients had resected
      lymph node number >=12 during operation, while other 407 patients had number <12.
      Univariate analysis showed that Borrmann type, depth of tumor invasion and
      resected lymph node number were associated with lymph node metastasis. Lymph node
      metastasis rates of Borrmann type I(, II(, III( and IIII( patients were 55.7%
      (34/61), 62.7% (192/306), 73.7% (264/358) and 51.2%(22/43) respectively, and the
      difference was statistically significant (chi2=18.115, P=0.000). Lymph node
      metastasis rates of T1, T2, T3, T4 stage patients were 0%(0/18), 30%(9/30),
      100%(9/9) and 69.5%(494/711) respectively, and the difference was statistically
      significant (chi2=63.971, P=0.000). Lymph node metastasis rate of patients with
      resected lymph node number >=12 was 79.5%(287/361), which was significantly
      higher than 55.3%(225/407) of those with resected lymph node number
      <12(chi2=50.496, P=0.000). Multivariate analysis revealed that higher T stage
      (OR=2.326, 95%CI: 1.758 to 3.078, P=0.000) and resected lymph node number
      >=12(OR=2.998, 95%CI: 2.142 to 4.195, P=0.000) were independent risk factors of
      lymph node metastasis. CONCLUSIONS: The lymph node metastasis rate of cardiac
      carcinoma is quite high. The metastasis occurs mainly in the surrounding of
      cardia, the small curvature of the stomach, the left artery of stomach and
      posterior pancreatic. The depth of tumor invasion and the number of lymph node
      dissection are independent risk factors of lymph node metastasis.

PMID- 29178101
TI  - [Clinicopathologic characteristics and prognosis analysis of 90 young patients
      with gastric cancer].
AB  - OBJECTIVE: To investigate the features of clinicopathology and prognosis in young
      gastric cancer patients. METHODS: Clinicopathological data of 90 young gastric
      cancer patients (<=40 years old) who received radical gastrectomy in the
      Department of General Surgery of Zhongshan Hospital, Fudan University from
      January 2013 to December 2014 were retrospectively analyzed. Survival data were
      obtained by follow-up and the last follow-up time was October 2016. Log-rank test
      and Cox regression model were used to analyze the risk factors of prognosis and
      these factors included gender, age, tumor size, degree of differentiation,
      histological type, Lauren pattern, T stage, N stage, vessel carcinoma embolus,
      clinical symptom, anemic condition, CA19-9 level, et al. RESULTS: The median age
      of 90 patients was 35 years old, of whom, 20(22.2%) patients were <=30 years old
      and 70(77.8%) patients were between 31 and 40 years old. There were 70(77.8%)
      female patients, 38(42.2%) patients with anemia, 11(12.8%) patients with elevated
      CA19-9 level and 9(10.0%) patients with family history of gastrointestinal
      tumors. The mean time of all the patients from presence of symptom to
      consultation was 8.2 months. Postoperative pathology revealed 65(72.2%) patients
      with poorly differentiated adenocarcinoma, 6(6.7%) patients with mucinous
      adenocarcinoma, 9(10%) patients with signet-ring cell carcinoma, and 10(11.1%)
      patients with papillary-canalicular adencarcinoma. Sixty-nine (76.7%) patients
      were diagnosed as advanced gastric cancer and 67(74.4%) patients were involved
      with lymphatic metastasis when they visited our hospital. Univariate analysis
      showed that gender (P=0.021), tumor size (P=0.001), depth of tumor infiltration
      (P=0.016), lymphatic metastasis (P=0.000), vessel carcinoma embolus (P=0.001),
      elevated CA19-9 level (P=0.001), and anemia (0.024) were statistically related
      with postoperative survival. Multivariate analysis showed that lymphatic
      metastasis was an independent risk factor of the poor prognosis of young patients
      (HR:2.774, 95%CI:1.435 to 5.364, P=0.002). CONCLUSIONS: The majority of young
      gastric cancer cases are female with poorly differentiated adenocarcinoma. Most
      patients are diagnosed as advanced gastric cancer with lymphatic metastasis when
      they visit hospital at the first time. The lymphatic metastasis is an independent
      risk factor of prognosis in young gastric cancer patients.

PMID- 29178102
TI  - [Value of serum human epithelial growth factor receptor 2 extracellular domain
      and circulating tumor cells in evaluating therapeutic response in advanced
      gastric cancer].
AB  - OBJECTIVE: To examine the correlation between serum human epithelial growth
      factor receptor 2 extracellular domain (HER2 ECD) and circulating tumor cells
      (CTC), as well as the dynamic variation of HER2 ECD and its correlation to the
      therapeutic efficacy. METHODS: Fifty-three advanced gastric cancer (AGC) patients
      who treated in Peking University Cancer Hospital and ever enrolled into CTC study
      (ClinicalTrial gov. ID: NCT01625702) were retrospectively included in this study.
      INCLUSION CRITERIA: the patients were histologically confirmed as locally
      advanced or recurrent and/or metastatic adencarcinoma; they received two or more
      cycles of fluorouracil-based chemotherapy or combination targeted therapy; serum
      CTC was counted before and after therapy; the clinical response was evaluated
      every 2 cycles of treatment by the presence of at least one measurable lesion
      according to RECIST version 1.1 criteria. This study was approved by Ethics
      Committee of Peking University Cancer Hospital, and informed consents were signed
      by patients. The sera before and after two cycles of treatment were collected for
      CTC enumeration and HER2 ECD detection, in which the levels of HER2 ECD were
      measured by chemiluminescence immunoassays method. The positive threshold value
      of HER2 ECD and CTC number were >=15 MUg/L and >=3 CTCs/7.5 ml respectively. The
      progression-free survival (PFS) and overall survival (OS) were compared among
      different groups using Log-rank tests. RESULTS: In 53 enrolled patients, 39 were
      histologically identified as negative HER2, 9 as positive HER2 and another 5
      cases were unknown. All the patients received fluorouracil-based chemotherapy,
      and 9 positive HER2 patients received combined anti-HER2 targeted therapy. Before
      therapy, the median HER2 ECD concentration of 53 cases was 10.45 (8.0 to 83.2)
      MUg/L. Seven patients exhibited positive HER2 ECD levels, in whom 4 were
      histologically HER2 positive, but 3 were histologically HER2 negative. The median
      CTC number of 53 cases was 2 (0 to 668) CTCs/7.5 ml, and the positive rate of CTC
      was 47.2%(25/53). Following 2 cycles of therapy, a total of 10 histologically
      HER2 negative patients exhibited positive HER2 ECD levels, in whom 2 also
      possessed positive HER2 ECD levels, 83.3 MUg/L and 46.9 MUg/L before therapy, and
      22.4 MUg/L and 20.4 MUg/L after therapy respectively, whereas another 8 patients
      (10.3 to 14.5 MUg/L before therapy) acquired the elevated expression of HER2 ECD
      following therapy (15.1 to 19.5 MUg/L). It seems that the increased level of HER2
      ECD after therapy was, though not statistically significant, correlated to low
      number of CTCs. In histologically HER2 negative patients, pretherapeutic HER2 ECD
      level (positive vs. negative) was not significantly correlated to PFS (7.6 months
      vs. 4.4 months, P=0.328) and OS (13.6 months vs. 10.9 months, P=0.679). However,
      in histologically HER2 positive patients, patients with positive HER2 ECD level
      before therapy exhibited longer PFS (10.7 months vs. 4.2 months, P=0.025) and OS
      (16.5 months vs. 8.9 months, P=0.015) compared to those with negative HER2 ECD
      level. Additionally, CTC number was significantly correlated to prognosis in
      histologically HER2 negative patients. Patients with positive pretherapeutic CTC
      number showed longer PFS (5.3 months vs. 3.3 months, P=0.049) and OS (14.3 months
      vs. 7.6 months, P=0.001) as well. While in histologically HER2 positive patients,
      CTC number was not obviously correlated to the PFS and OS. In above 8 negative
      HER2 patients acquiring elevated expression of HER2 ECD following therapy, the
      increased HER2 ECD level was not correlated to PFS and OS (all P>0.05). In 9
      histologically HER2 positive patients, 4 patients who exhibited decreased HER2
      ECD level and reduced or constant CTC number had longer PFS (7.5 to 15.3 months)
      and OS (11.0 to 26.3 months) compared with those 2 patients who suffered from
      acquired HER2 ECD level following therapy (PFS 3.0 to 4.8 months and OS 7.3 to
      8.6 months). CONCLUSIONS: In histologically HER2 positive patients, increased
      pretherapeutic HER2 ECD level predicts better prognosis. The acquired elevated
      HER2 ECD level following therapy is correlated to inefficient therapeutic
      response. The acquirement of elevated HER2 ECD level can also be found in
      histologically HER2 negative patients, which may be correlated to the
      corresponding variation of CTC number.

PMID- 29178104
TI  - [Susceptibility genes and serum markers of intestinal fibrosis in Crohn disease].
AB  - Crohn disease (CD) is a chronic inflammatory disease which progressively affects
      the digestive tract with unknown etiology. During the disease course, intestinal
      fibrosis will gradually develop in many CD patients and results in irreversible
      fibrosis stricture, causing refractory abdominal pain and even intestinal
      obstruction, and necessitating one or more surgical interventions. Thus far the
      exact etiology of CD remains unknown. It is believed that genetic, environmental
      and immunologic factors are involved, which may also predict the development of
      intestinal fibrosis. Recent studies have found the association of mutations in
      genes, such as NOD2, ATG16L1, CX3CR1, IL-23R and MMP3 with the fibrogenic
      phenotype of CD. In addition, serum extracellular matrix molecules, growth
      factors, miRNAs and microbial antibodies have also been linked to the
      fibrogenesis in CD patients, however the results of researches were divergent.
      Therefore it is of significance to explore noninvasive markers of intestinal
      fibrosis with high sensitivity and specificity, and the high-throughput proteomic
      technique may be an approach that deserves further investigation. Screening the
      high-risk patients for the fibrostenotic phenotype of CD by susceptibility genes,
      and early detection of intestinal fibrosis using noninvasive serum markers, will
      help improve the treatment outcomes and reduce the surgical rates. The article
      aims at summarizing the current susceptibility genes and serum markers of
      intestinal fibrosis in CD.

PMID- 29178103
TI  - [Influence of CCL21 on the invasion and metastasis of colorectal cancer].
AB  - OBJECTIVE: To investigate the influence of CCL21 on the invasion and metastasis
      of colorectal cancer (CRC). METHODS: CCL21 over-expressing CRC cell line was
      constructed by lentivirus infection and CCL21 low-expressing CRC cell line was
      constructed by lipofection. The effects of CCL21 on the invasion and metastasis
      of CRC cells and the stem cell-like phenotype were investigated by Transwell
      migration, invasion assay, wound healing assay and sphere formation assay.
      RESULTS: Real-time quantitative PCR and western blot confirmed that the
      expression of CCL21 was up-regulated by lentiviral transfection and down
      regulated by siRNA liposome transfection. In vitro, Transwell assays showed that
      the invasion and migration in CCL21 over-expressing CRC cells decreased
      significantly as compared to those of CCL21 low-expressing cells. In wound
      healing assay, the CCL21 over-expressing CRC cells showed a significantly lower
      rate of migration. In addition, the sphere formation rate and density of CCL21
      over-expressing CRC cells were lower than those with low-expression of CCL21.
      CONCLUSION: CCL21 can suppress the migration and invasion of CRC cells and weaken
      their stem cell-like phenotype.

PMID- 29178105
TI  - [Translation into Spanish and a preliminary analysis of the psychometric
      properties of the Newcastle Stroke-Specific Quality of Life Measure (NEWSQOL)
      questionnaire for rating the quality of life among post-stroke patients].
AB  - INTRODUCTION: The Newcastle Stroke-Specific Quality of Life Measure (NEWSQOL) is
      one of the few specific questionnaires for evaluating the quality of life among
      patients who have suffered an ischaemic or haemorrhagic stroke. AIMS: To
      translate and adapt this questionnaire into Spanish and to evaluate its
      reliability and acceptability. PATIENTS AND METHODS: The original version of the
      NEWSQOL questionnaire was translated into Spanish. The translation was agreed
      upon by a team of experts, and was then back-translated into English and sent to
      the author, who gave her approval of the rendering. This version was later
      administered to a group of patients in order to evaluate its reliability,
      acceptability, floor effect and ceiling effect. RESULTS: The process of
      linguistic adaptation allowed semantic, conceptual and content equivalence to be
      achieved in the Spanish version of the NEWSQOL. The results obtained in the
      preliminary analysis show excellent acceptability, an internal consistency index
      of 0.9 for the whole questionnaire and a good or excellent test-retest agreement
      for all the domains. No ceiling effect was detected, but a floor effect was
      observed in the case of the vision and cognition domains. CONCLUSION: The Spanish
      version of the NEWSQOL questionnaire is reliable for evaluating the quality of
      life in post-stroke patients, as well as being well accepted. The questionnaire
      must be used in more broader samples in order to evaluate its validity and
      sensitivity.

PMID- 29178106
TI  - [The level of knowledge regarding the concept of brain death among undergraduates
      at the Universitat de Lleida].
AB  - INTRODUCTION: Brain death is a death situation which is diagnosed by means of
      neurological criteria and is the ideal situation for organ donation, as, thanks
      to intensive care, the organs maintain their viability. Very few studies have
      analysed the knowledge that the population has about this situation. AIM: To
      determine how much university students know about brain death by comparing the
      results between undergraduates pursuing a degree in medicine and those on other
      bachelor's degree courses. SUBJECTS AND METHODS: A closed on-line survey was
      administered to undergraduate students at the Universitat de Lleida about their
      knowledge regarding the concept of brain death, donor legislation and willingness
      to donate. RESULTS: The survey was answered by a total of 488 people, 192 (39.3%)
      from the degree in medicine. Only 164 (33.6%) were males. The mean age was 22.1
      +/- 4.4 years. Only 63 (12.9%) respondents defined brain death as death. While
      19.1% replied correctly to the question about organ donation legislation, 79.7%
      said they would be willing to donate their organs. The level of knowledge was
      significantly higher in the later courses of the degree in medicine, although
      there was still plenty of room for improvement in this respect. Only 31.7% of
      sixth-year students had a good idea of the concept of brain death. CONCLUSION:
      The extent of knowledge about brain death and legislation on organ donation is
      poor among university students, even in the degree in medicine. It would be
      advisable to design strategies aimed at improving this knowledge, especially
      among future healthcare professionals.

PMID- 29178107
TI  - [A study of the demand for health care in hereditary-metabolic diseases in a
      Spanish tertiary care hospital].
AB  - AIM: To determine the characteristics of the demand for health care in hereditary
      metabolic diseases in a Spanish tertiary care hospital. PATIENTS AND METHODS: We
      conducted a retrospective descriptive study involving a review of the
      epidemiological data, reasons for visiting, diagnoses and complementary studies
      of the patients treated by a metabolic disease unit over a period of 6 years and
      11 months. RESULTS: Altogether 1012 patients were evaluated. There was a
      predominance of males (52%) and of patients under the age of 1 year (42.09%).
      71.44% of them were under 6 years old. Approximately half of the patients (50.3%)
      came from hospitals (wards, outpatients, neonatology, emergency department,
      neuropaediatrics and intensive care), followed by the neonatal screening
      programme (20.36%) and primary care (14.82%). The most frequent reasons for
      visiting and diagnoses can be seen in their respective tables. CONCLUSIONS: The
      study of the demand for health care in hereditary-metabolic diseases is useful as
      a means to detect needs in their field and to try to adapt care to meet them.
      Medical, scientific and social progress makes it necessary to have an expert in
      metabolism present in reference clinical units. As members of multidisciplinary
      teams alongside other specialists, they will contribute towards accomplishing a
      suitable presumptive diagnosis, diagnosis, management and follow-up. It is
      necessary to keep them constantly up-to-date and ensure adequate training of new
      experts in metabolism, since this is the best way to deliver optimal care for
      those with metabolic illnesses, which are usually rare diseases.

PMID- 29178108
TI  - [Iodinated contrast-induced encephalopathy: a pathology that must be borne in
      mind when carrying out endovascular examinations].
AB  - INTRODUCTION: In recent years there has been an increase in the number of
      endovascular examinations in the study of both cardiovascular and cerebrovascular
      diseases. One very infrequent complication is neurotoxicity due to contrast, and
      it must be suspected within the context of a neurological deficit following such
      examinations in order to be able to diagnose it. CASE REPORT: A 61-year-old male
      who presented an epileptic attack and later deficit in the left hemisphere
      following diagnostic arteriography. After ruling out the possibility of an urgent
      vascular pathology, he was submitted to a magnetic resonance brain scan with the
      suspicion of this condition. The clinical signs and symptoms were limited to 72
      hours with cortisone therapy. CONCLUSIONS: Contrast-induced encephalopathy covers
      a wide range of clinical features which, in the vast majority of cases, are self
      limiting to 24-72 hours, and within the context of neuronal damage following
      contrast infusion. Its prognosis is excellent, and diagnostic suspicion is
      crucial in its treatment.

PMID- 29178110
TI  - [42.a Reunion de la Sociedad de Neurofisiologia Clinica de las Comunidades de
      Valencia y Murcia. Communications].

PMID- 29178109
TI  - [Effects of cocaine on prepulse inhibition of the startle response].
AB  - INTRODUCTION: Prepulse inhibition (PPI) of the startle response is an index used
      to evaluate how the pre-attention system works. PPI is altered in patients with a
      mental disorder such as schizophrenia and in subjects who are vulnerable to it.
      Likewise, cocaine users also frequently exhibit psychiatric disorders as
      schizophrenia. AIM: To know the alterations that cocaine produces on PPI.
      DEVELOPMENT: A comprehensive review is carried out, covering both clinical and
      preclinical studies with animal models that have evaluated the effects of cocaine
      exposure on the PPI paradigm. Underlying neural bases and mechanisms of action
      are suggested to explain these findings. CONCLUSIONS: Cocaine alters PPI through
      its action on the dopaminergic system. Acute exposure of cocaine decreases PPI by
      increasing dopamine, while with chronic use, depending on withdrawal time, PPI
      can be restored. However, the effects of cocaine on PPI appear to depend on the
      baseline levels of PPI shown by the individual. Thus, since a deficit in PPI has
      been associated with a greater vulnerability to developing mental pathologies
      such as schizophrenia, PPI level in subjects could be considered as a biomarker
      of psychiatric vulnerability. Therefore, a better understanding of the effect of
      drugs such as cocaine on PPI may help to understand the development of dual
      pathology.

PMID- 29178111
TI  - [Progressive encephalitis due to anti-DPPX antibodies: a case with good response
      to treatment with rituximab].

PMID- 29178112
TI  - [Encephalopathy due to human herpesvirus 6 in a western immunocompetent patient].

PMID- 29178113
TI  - The push to eradicate poliomyelitis in the Eastern Mediterranean Region.

PMID- 29178114
TI  - Outcomes of children with attention deficit/hyperactivity disorder: global
      functioning and symptoms persistence.
AB  - Many adolescents with ADHD show antisocial behaviour and low educational
      achievement. These issues have not been validated in the World Health
      Organization Eastern Mediterranean Region. The objective of this study was to
      assess the global functioning and behaviour of children with ADHD growing into
      adolescence 10 years after initial diagnosis. Parents were interviewed using a
      structured questionnaire, Conner's Short Version Test and the Children's Global
      Assessment Scale. Nearly half of our sample had low academic achievement and 36%
      had no friends. A quarter of the cases were smokers, one admitted abusing drugs
      and one had attempted suicide. One third of the sample continued to have ADHD
      symptoms. Adolescents with ADHD had similar school performance and peer
      relationships to those reported previously, but differences with regard to drug
      use, suicide and other impulsive behaviour. A follow-up study into adult life
      using a control group is recommended.

PMID- 29178115
TI  - Multiplex polymerase chain reaction-based serotype analysis of dengue virus
      during 2015 dengue outbreak in Pakistan.
AB  - Dengue is one of the most important arthropod-borne viral diseases. It is endemic
      in > 125 countries including Pakistan, with a global incidence of 50-200 million.
      We determined the frequency of different serotypes of dengue virus to highlight
      its hyperendemicity in Rawalpindi, Pakistan. Between May and October 2015 we
      analysed the serum samples of 140 patients with a suspicion of dengue, using
      ELISA and multiplex polymerase chain reaction. One hundred and eight were
      infected with serotype 2, 16 with serotype 3, 7 with serotype 4 and 3 with
      serotype 1. Three patients were infected with serotypes 1 and 2, and 1 each with
      serotypes 1 and 4 and serotypes 2 and 3. Incidence of dengue has increased many
      fold in the past 50 years and has expanded to areas that were previously free
      from the disease. Serotype 2 was predominant in our population followed by
      serotype 3. There is currently no specific treatment for dengue, and vector
      control and vaccination are the only effective methods to prevent future
      outbreaks.

PMID- 29178116
TI  - Third study on WHO MPOWER Tobacco Control Scores in Eastern Mediterranean
      countries 2011-2015.
AB  - This study was conducted to quantify the implementation of the MPOWER policies
      and to assess any possible changes across Eastern Mediterranean Region (EMR)
      countries. In this comparative cross-sectional study based on 10 categories
      mentioned in MPOWER report 2015 a checklist was designed. Seven questions were
      scored from 0-4 and three from 0-3. The 22 EMR countries were ranked and compared
      by their total score on a scale of 0-37. The highest scores were achieved by
      Egypt and the Islamic Republic of Iran. Pakistan, Sudan and Yemen showed
      progress, while Bahrain, Jordan, Kuwait, Oman, and the Syrian Arab Republic had
      decreased scores. The total score of the EMR countries had decreased compared to
      2013. Thus, there remains a need for greater focus on tobacco taxation and smoke
      free policies to address this retrograde step.

PMID- 29178117
TI  - Mood and anxiety disorders among adolescent students in Jordan.
AB  - Mental disorders in adolescents have negative impacts on aspects of health and
      life that can be reduced by early detection and referral. This study aimed to
      estimate the prevalence of mood and anxiety disorders and to investigate their
      association with gender and other socio-demographic factors among adolescent
      students. A descriptive cross-sectional design was used in this study. A sample
      of 1103 adolescent students was recruited from schools who completed the first
      two sections of Patient Health Questionnaire for Adolescents (PHQ-A). The
      prevalence of any mental disorders was 28.6%. The prevalence of mood and anxiety
      disorders was 22.4% and 16.3%, respectively. Significant associations were found
      between mental disorders and gender, age, living status with parents, or mental
      health status of parents. Further studies are needed to be conducted in Jordan in
      order to understand the nature and risk factors of mental disorders among
      adolescents. School and community-based mental health screening, promotion and
      prevention programmes are recommended to prevent and reduce the prevalence of
      mental disorders among adolescents.

PMID- 29178118
TI  - Midwives' educational needs and knowledge about sexually transmittable infections
      in the Islamic Republic of Iran.
AB  - This study aimed to evaluate the educational needs and knowledge about sexually
      transmittable infections (STIs) demonstrated by midwives. In a cross-sectional
      study in 2014, 144 midwives in Rasht, Islamic Republic of Iran, were surveyed.
      The Persian version of the Sexually Transmitted Disease Knowledge Questionnaire
      (STD-KQ) and a researcher-made questionnaire to evaluate educational needs and
      profile were used. The participants obtained 74% of the total score of STD-KQ.
      Thirty-one percent of participants were categorized in high or very high need of
      education. Seventy percent of midwives mentioned they were trained on all STIs at
      university. However, only 6.3% of midwives were aware of existing STIs
      guidelines. Participants reported that in the last two years they were only
      educated about HIV/AIDS and hepatitis B at their workplace. Thus, a comprehensive
      educational programme to empower midwives for complete STIs control is
      recommended.

PMID- 29178119
TI  - Development of an Eastern Mediterranean Region search strategy for biomedical
      citations indexed in PubMed.
AB  - PubMed, a 'barrier-free' bibliographic database covering biomedical and health
      disciplines, has been successfully used to identify a multitude of indicators
      that assist in analyzing global trends for biomedical research productivity. The
      current study represents an original attempt to develop and optimize an Eastern
      Mediterranean Region (EMR) search strategy in PubMed to pave the way for
      subsequent descriptive analyses. The refined EMR search strategy contains
      elaborate syntaxes which facilitate controlling the search process and
      maintaining a proper balance between sensitivity and precision of the obtained
      results. Country-specific citation data were manually scanned for false positive
      publications. Our results indicate that publication productivity increased nearly
      five-fold in the EMR from 2004 to 2013. Five countries (Islamic Republic of Iran,
      Egypt, Saudi Arabia, Tunisia and Pakistan; in order of total publications)
      contributed to 80% of all EMR publications during this period. Each of the
      remaining 17 EMR countries contributed less than 4%. We believe that the
      methodology presented in this study can be used in conjunction with other metrics
      to extract invaluable indicators to describe EMR health research systems.

PMID- 29178120
TI  - Awareness, attitudes and knowledge about evidencebased medicine among doctors in
      Gaza: a crosssectional survey.
AB  - Evidence-based medicine (EBM) has emerged as a strategy to integrate research
      evidence within clinical decision-making. We have explored awareness, knowledge
      and attitudes about EBM among doctors in the Gaza Strip. In 2014, we conducted a
      cross-sectional survey among doctors working in health centres in Gaza, using a
      20 item, web-based self-administered questionnaire. Approximately two thirds of
      the respondents welcomed EBM in principle, and believed that it could improve
      patient care. However, they had a relatively low level of knowledge about EBM.
      The main barriers to EBM mentioned by respondents were lack of knowledge needed
      to practise EBM [n = 47 (35%)]; negative attitude among senior colleagues [n = 34
      (25%)]; lack of relevant resources [n = 31 (23%)]; work overload [n = 27 (20%)];
      and lack of institutional support [n = 248 (18%)]. Thus, there are personal and
      organisational barriers to its practice that need to be addressed.

PMID- 29178121
TI  - Study of congenital heart diseases in patients with Down syndrome in Algeria.
AB  - This study aimed to describe and evaluate the type, frequency and patterns of
      congenital heart diseases (CHDs) in patients with Down Syndrome (DS) in Setif,
      Algeria. Down Syndrome, or trisomy 21, is the most common genetic disorder in the
      world. Data were collected and followed from January 2009 to December 2013.
      Parental consanguinity documenting pedigree analyzing, chromosome analysis and
      clinical examination were carried out for all cases. Results have shown that 22
      (15.4%; +/- 0.06) of the total 143 known cases of DS from DS centres have CHDs
      and 88 (10.6%; +/- 2.2) of the total 770 patients with CHDs collected from public
      departments at the child and maternity teaching hospital, Setif, have DS. Among
      the 110 cases, 75 (68%) have single cardiac abnormalities and 35 (32%) have
      multiple cardiac abnormalities. The most frequent CHDs were Atrioventricular
      Septal Defect (AVSD). In conclusion, our study will be helpful to demonstrate the
      current status of DS and to identify the distribution of CHD in patients with DS
      in Setif, Algeria, for further study.

PMID- 29178122
TI  - Evaluation of biomedical waste management in primary health care centres in Saudi
      Arabia: a knowledge, attitudes and practices study.
AB  - Awareness and knowledge of biomedical waste practices is very important for any
      health care setting. This study aimed to determine the knowledge, attitudes and
      practices (KAP) about biomedical waste among health professionals in primary
      health care centres in Hail City, Saudi Arabia. The study included 135 of 155
      professionals who dealt with biomedical waste from 16 out of 26 primary health
      care centres. Data were collected using a structured questionnaire. Overall
      54.8%, 48.9% and 49.6% of the participants had good knowledge, attitudes and
      practices scores respectively. Profession, education and age were significantly
      associated with KAP level (P < 0.01): doctors, those with a degree and older
      respondents had better KAP scores. There was a strong correlation between
      knowledge and attitudes, knowledge and practices, and attitudes and practices (P
      ? 0.05). Training is recommended to enhance the knowledge of the professionals
      dealing with biomedical waste in the primary health care centres.

PMID- 29178123
TI  - WHO events addressing public health priorities.

PMID- 29178124
TI  - High cut-off membranes in acute kidney injury and continuous renal replacement
      therapy.
AB  - Innovation in continuous renal replacement therapies (CRRT) utilized to treat
      acute kidney injury (AKI) and sepsis, has brought new machines and techniques.
      Part of these new advances are due to the availability of innovative biomaterials
      and the construction of membranes with larger pores and wide distribution of pore
      sizes. This includes the creation of a new generation of high cut-off membranes
      whose utilization in clinical practice is promising for the wide spectrum of
      solutes that are removed during extracorporeal therapies.However, the enlargement
      of pore diameters brings some loss of albumin during treatment and this effect is
      still under evaluation, since there is a possibility that this is detrimental for
      the patient. A thorough review of the available clinical literature is reported
      in this paper with a reappraisal of the potential application of these new
      technologies.

PMID- 29178125
TI  - Laparoscopic versus open resection for sigmoid diverticulitis.
AB  - BACKGROUND: Diverticular disease is a common condition in Western industrialised
      countries. Most individuals remain asymptomatic throughout life; however, 25%
      experience acute diverticulitis. The standard treatment for acute diverticulitis
      is open surgery. Laparoscopic surgery - a minimal-access procedure - offers an
      alternative approach to open surgery, as it is characterised by reduced operative
      stress that may translate into shorter hospitalisation and more rapid recovery,
      as well as improved quality of life. OBJECTIVES: To evaluate the effectiveness of
      laparoscopic surgical resection compared with open surgical resection for
      individuals with acute sigmoid diverticulitis. SEARCH METHODS: We searched the
      following electronic databases: the Cochrane Central Register of Controlled
      Trials (CENTRAL; 2017, Issue 2) in the Cochrane Library; Ovid MEDLINE (1946 to 23
      February 2017); Ovid Embase (1974 to 23 February 2017); clinicaltrials.gov
      (February 2017); and the World Health Organization (WHO) International Clinical
      Trials Registry (February 2017). We reviewed the bibliographies of identified
      trials to search for additional studies. SELECTION CRITERIA: We included
      randomised controlled trials comparing elective or emergency laparoscopic sigmoid
      resection versus open surgical resection for acute sigmoid diverticulitis. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected studies,
      assessed the domains of risk of bias from each included trial, and extracted
      data. For dichotomous outcomes, we calculated risk ratios (RRs) with 95%
      confidence intervals (CIs). For continuous outcomes, we planned to calculate mean
      differences (MDs) with 95% CIs for outcomes such as hospital stay, and
      standardised mean differences (SMDs) with 95% CIs for quality of life and global
      rating scales, if researchers used different scales. MAIN RESULTS: Three trials
      with 392 participants met the inclusion criteria. Studies were conducted in three
      European countries (Switzerland, Netherlands, and Germany). The median age of
      participants ranged from 62 to 66 years; 53% to 64% were female. Inclusion
      criteria differed among studies. One trial included participants with Hinchey I
      characteristics as well as those who underwent Hartmann's procedure; the second
      trial included only participants with "a proven stage II/III disease according to
      the classification of Stock and Hansen"; the third trial considered for inclusion
      patients with "diverticular disease of sigmoid colon documented by colonoscopy
      and 2 episodes of uncomplicated diverticulitis, one at least being documented
      with CT scan, 1 episode of complicated diverticulitis, with a pericolic abscess
      (Hinchey stage I) or pelvic abscess (Hinchey stage II) requiring percutaneous
      drainage."We determined that two studies were at low risk of selection bias; two
      that reported considerable dropouts were at high risk of attrition bias; none
      reported blinding of outcome assessors (unclear detection bias); and all were
      exposed to performance bias owing to the nature of the intervention.Available low
      quality evidence suggests that laparoscopic surgical resection may lead to little
      or no difference in mean hospital stay compared with open surgical resection (3
      studies, 360 participants; MD -0.62 (days), 95% CI -2.49 to 1.25; I2 = 0%).Low
      quality evidence suggests that operating time was longer in the laparoscopic
      surgery group than in the open surgery group (3 studies, 360 participants; MD
      49.28 (minutes), 95% CI 40.64 to 57.93; I2 = 0%).We are uncertain whether
      laparoscopic surgery improves postoperative pain between day 1 and day 3 more
      effectively than open surgery. Low-quality evidence suggests that laparoscopic
      surgery may improve postoperative pain at the fourth postoperative day more
      effectively than open surgery (2 studies, 250 participants; MD = -0.65, 95% CI 
      1.04 to -0.25).Researchers reported quality of life differently across trials,
      hindering the possibility of meta-analysis. Low-quality evidence from one trial
      using the Short Form (SF)-36 questionnaire six weeks after surgery suggests that
      laparoscopic intervention may improve quality of life, whereas evidence from two
      other trials using the European Organization for Research and Treatment of Cancer
      core quality of life questionnaire (EORTC QLQ-C30) v3 and the Gastrointestinal
      Quality of Life Index score, respectively, suggests that laparoscopic surgery may
      make little or no difference in improving quality of life compared with open
      surgery.We are uncertain whether laparoscopic surgery improves the following
      outcomes: 30-day postoperative mortality, early overall morbidity, major and
      minor complications, surgical complications, postoperative times to liquid and
      solid diets, and reoperations due to anastomotic leak. AUTHORS' CONCLUSIONS:
      Results from the present comprehensive review indicate that evidence to support
      or refute the safety and effectiveness of laparoscopic surgery versus open
      surgical resection for treatment of patients with acute diverticular disease is
      insufficient. Well-designed trials with adequate sample size are needed to
      investigate the efficacy of laparoscopic surgery towards important patient
      oriented (e.g. postoperative pain) and health system-oriented outcomes (e.g. mean
      hospital stay).

PMID- 29178126
TI  - A comparison between McGrath MAC videolaryngoscopy and Macintosh laryngoscopy in
      children.
AB  - BACKGROUND: This prospective, randomised, controlled study was performed to
      evaluate the usefulness of the McGrath VL compared with Macintosh laryngoscopy in
      children with expected normal airway during endotracheal intubation, by comparing
      the time to intubation and difficulty of intubation. METHODS: Eighty-four
      patients aged 1-10 years who underwent endotracheal intubation for elective
      surgery were randomly assigned to the McGrath group (n = 42) or the Macintosh
      group (n = 42). Anaesthesia was induced with 2.5-3.0 mg/kg of propofol and
      sevoflurane 5-8 vol%. Orotracheal intubation was performed 2 min after injection
      of rocuronium 0.6 mg/kg with McGrath VL or Macintosh laryngoscope; the primary
      outcome was the time to intubation. The Cormack and Lehane glottic grade,
      intubation difficulty score (IDS), and success rate on intubation were assessed.
      Haemodynamic changes were also recorded. RESULTS: As the primary outcome, median
      time to intubation [interquartile range] did not differ between the McGrath group
      and the Macintosh group (25.0 [22.8-28.3] s vs. 26.0 [24.0-29.0] s, P = 0.301).
      The incidence of grade I glottic view was significantly higher in the McGrath
      group than in the Macintosh group (95% vs. 74%, P = 0.013). Median IDS was lower
      in the McGrath group than in the Macintosh group (0 [0-0] vs. 0 [0-1], P =
      0.018). There were no significant differences in success rate on intubation or
      haemodynamics between the two groups. CONCLUSIONS: McGrath VL provides better
      laryngeal views and lower IDS but similar intubation times and success rates
      compared with the Macintosh laryngoscope in children with normal airway.

PMID- 29178127
TI  - Social Integration and the Mental Health of Black Adolescents.
AB  - The influence of family, school, and religious social contexts on the mental
      health of Black adolescents has been understudied. This study used Durkheim's
      social integration theory to examine these associations in a nationally
      representative sample of 1,170 Black adolescents, ages 13-17. Mental health was
      represented by positive and negative psychosocial well-being indicators. Results
      showed that adolescents' integration into family and school were related to
      better mental health. In addition, commitment to religious involvement positively
      influenced mental health. Although the direct effect of religious involvement was
      inversely related to mental health, mediation analyses revealed a positive
      influence through religious commitment. Findings suggest a greater emphasis on
      all three social contexts when designing strategies to improve the mental health
      of Black adolescents.

PMID- 29178128
TI  - The origin and evolution of coral species richness in a marine biodiversity
      hotspot.
AB  - The Coral Triangle (CT) region of the Indo-Pacific realm harbors an extraordinary
      number of species, with richness decreasing away from this biodiversity hotspot.
      Despite multiple competing hypotheses, the dynamics underlying this regional
      diversity pattern remain poorly understood. Here, we use a time-calibrated
      evolutionary tree of living reef coral species, their current geographic ranges,
      and model-based estimates of regional rates of speciation, extinction, and
      geographic range shifts to show that origination rates within the CT are lower
      than in surrounding regions, a result inconsistent with the long-standing center
      of origin hypothesis. Furthermore, endemism of coral species in the CT is low,
      and the CT endemics are older than relatives found outside this region. Overall,
      our model results suggest that the high diversity of reef corals in the CT is
      largely due to range expansions into this region of species that evolved
      elsewhere. These findings strongly support the notion that geographic range
      shifts play a critical role in generating species diversity gradients. They also
      show that preserving the processes that gave rise to the striking diversity of
      corals in the CT requires protecting not just reefs within the hotspot, but also
      those in the surrounding areas.

PMID- 29178129
TI  - Depression and somatic symptoms in Japanese and American college students:
      Negative mood regulation expectancies as a personality correlate.
AB  - This study clarified contradictory findings regarding whether depression and
      somatic symptoms are associated more strongly with each other in non-Western
      countries than in Western countries, by examining the relationships of the two
      variables with negative mood regulation expectancies (NMRE). NMRE are beliefs
      about one's ability to improve one's negative moods. Participants were 155
      Japanese and 176 American undergraduates. They completed self-report measures of
      NMRE, coping, depression and somatic symptoms. Results showed that depression
      significantly correlated with somatic symptoms for both men and women in both
      countries, and there was no cultural difference in the relationship between
      depression and somatic symptoms. The relationships of depression and somatic
      symptoms with NMRE did not differ between cultures. NMRE explained variance in
      depression in both countries but variance in somatic symptoms only for women in
      both countries. The relationship of NMRE with depression and somatic symptoms
      paralleled that between depression and somatic symptoms for both cultures. These
      results were consistent with the previous literature that found no difference
      between cultures. Results support the cross-cultural validity of measuring NMRE
      in the context of coping and distress.

PMID- 29178130
TI  - Comorbid "treatable traits" in difficult asthma: Current evidence and clinical
      evaluation.
AB  - The care of patients with difficult-to-control asthma ("difficult asthma") is
      challenging and costly. Despite high-intensity asthma treatment, these patients
      experience poor asthma control and face the greatest risk of asthma morbidity and
      mortality. Poor asthma control is often driven by severe asthma biology, which
      has appropriately been the focus of intense research and phenotype-driven
      therapies. However, it is increasingly apparent that extra-pulmonary
      comorbidities also contribute substantially to poor asthma control and a
      heightened disease burden. These comorbidities have been proposed as "treatable
      traits" in chronic airways disease, adding impetus to their evaluation and
      management in difficult asthma. In this review, eight major asthma-related
      comorbidities are discussed: rhinitis, chronic rhinosinusitis, gastroesophageal
      reflux, obstructive sleep apnoea, vocal cord dysfunction, obesity, dysfunctional
      breathing and anxiety/depression. We describe the prevalence, impact and
      treatment effects of these comorbidities in the difficult asthma population,
      emphasizing gaps in the current literature. We examine the associations between
      individual comorbidities and highlight the potential for comorbidity clusters to
      exert combined effects on asthma outcomes. We conclude by outlining a pragmatic
      clinical approach to assess comorbidities in difficult asthma.

PMID- 29178131
TI  - The rapid-onset antidepressant effect of ketamine: More surprises?
AB  - WHAT IS KNOWN AND OBJECTIVE: An effective rapid-onset treatment for major
      depressive disorder could save lives. Extensive preclinical and clinical data
      demonstrate such an action of ketamine. However, the presumptive mechanism of
      action, inhibition of NMDA (N-methyl-D-aspartate) receptors, has recently been
      challenged. Elucidation of the mechanism is important clinically for drug
      discovery and for understanding the (patho)physiology of depression. COMMENT: The
      best-known pharmacologic property of ketamine is non-competitive inhibition of
      the NMDA subtype of glutamate receptor. Although other mechanisms have been
      postulated, this action has been assumed the major one that accounts for
      ketamine's antidepressant effect. However, a ketamine metabolite and a different
      mechanism have now been claimed to be necessary and sufficient for the effect.
      WHAT IS NEW AND CONCLUSION: A metabolite has been proposed to be responsible for
      the antidepressant action of ketamine, via activation of non-NMDA receptors. It
      will be important to determine which of the competing views is correct.

PMID- 29178132
TI  - Thrombopoietin receptor agonists for prevention and treatment of chemotherapy
      induced thrombocytopenia in patients with solid tumours.
AB  - BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is defined as a
      peripheral platelet count less than 100*109/L, with or without bleeding in cancer
      patients receiving myelosuppressive chemotherapy. CIT is a significant medical
      problem during chemotherapy, and it carries the risk of sub-optimal overall
      survival and bleeding. Alternative interventions to platelet transfusion are
      limited. Different stages of preclinical and clinical studies have examined the
      thrombopoietin receptor agonists (TPO-RAs) for CIT in patients with solid
      tumours. OBJECTIVES: To assess the effects of TPO-RAs to prevent and treat CIT in
      patients with solid tumours:(1) to prevent CIT in patients without
      thrombocytopenia before chemotherapy, (2) to prevent recurrence of CIT, and (3)
      to treat CIT in patients with thrombocytopenia during chemotherapy. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL,
      to 28 September 2017), MEDLINE (from 1950 to 28 September 2017), as well as
      online registers of ongoing trials (Clinical Trials, Chinese Clinical Trial
      Register, Australian New Zealand Clinical Trial Registry, WHO ICTRP Search
      Portal, International Standard Randomised Controlled Trial Number registry,
      GlaxoSmithKline Clinical Study Register, and Amgen Clinical Trials) and
      conference proceedings (American Society of Hematology, American Society of
      Clinical Oncology, European Hematology Association, European Society of Medical
      Oncology, and Conference Proceedings Citation Index-Science, from 2002 up to
      September 2017) for studies. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing TPO-RAs alone, or in combination with other drugs, to placebo,
      no treatment, other drugs, or another TPO-RAs for CIT in patients with solid
      tumours. DATA COLLECTION AND ANALYSIS: Two review authors independently screened
      the results of the search strategies, extracted data, assessed risk of bias, and
      analysed data according to standard methodological methods expected by Cochrane.
      MAIN RESULTS: We identified six trials eligible for inclusion, of which two are
      ongoing, and one awaiting classification study. The three included trials were
      conducted at many different sites in Europe, America, and Asia. All of the three
      studies recruited adult and elder participants (no children were included) with
      solid tumours, and compared TPO-RAs with placebo. No studies compared TPO-RAs
      alone, or in combination with other drugs, to no treatment, or other drugs, or
      another TPO-RAs.We judged the overall risk of bias as high as we found a high
      risk for detection bias. We assessed the risk of bias arising from inadequate
      blinding of outcome assessors as high for number and severity of bleeding
      episodes (one of the primary outcomes).To prevent CIT: We included two trials
      (206 participants) comparing TPO-RAs (eltrombopag, multiple-dose oral
      administration with chemotherapy) with placebo. The use of TPO-RAs may make
      little or no difference to the all-cause mortality at 33 weeks of follow-up (RR
      1.35, 95% CI 0.53 to 3.45; one trial, 26 participants; low quality of evidence).
      There is not enough evidence to determine whether TPO-RAs reduce the number of
      patients with at least one bleeding episode of any severity (RR 0.62, 95% CI 0.22
      to 1.78; two trials, 206 participants; very low quality of evidence). There is
      not enough evidence to determine whether TPO-RAs reduce the number of patients
      with at least one severe/life-threatening bleeding episode (RR 0.36, 95% CI 0.06
      to 2.06; two trials, 206 participants; very low quality of evidence). No studies
      were found that looked at overall survival (one of the primary outcomes), the
      number of treatment cycles with at least one bleeding episode, the number of days
      on which bleeding occurred, the amount of bleeding, or quality of life.To prevent
      recurrence of CIT: We included one trial (62 participants) comparing TPO-RAs
      (romiplostim, single-dose subcutaneous administration with chemotherapy) with
      placebo. There is not enough evidence to determine whether TPO-RAs reduce the
      number of patients with at least one bleeding episode of any severity (RR 2.80,
      95% CI 0.17 to 47.53; one trial, 62 participants; very low quality of evidence).
      There is not enough evidence to determine whether TPO-RAs reduce the number of
      patients with at least one severe/life-threatening bleeding episode (no
      severe/life-threatening bleeding episodes; one trial, 62 participants; very low
      quality of evidence). No studies were found that looked at overall survival (one
      of the primary outcomes), the number of treatment cycles with at least one
      bleeding episode, the number of days on which bleeding occurred, the amount of
      bleeding, or quality of life. We found one ongoing study (expected recruitment 74
      participants), it is planned to give TPO-RAs (romiplostim, subcutaneous
      administration with chemotherapy) to participants, but to date this trial has not
      reported any outcomes.To treat CIT: We found one ongoing study (expected
      recruitment 83 participants), which is planned to give TPO-RAs (eltrombopag,
      seven days orally) to participants when their platelet counts are less than
      75*109/L during chemotherapy. This trial was originally planned to complete in
      March 2017, however, the completion date has passed and no results are
      reported.The one awaiting classification study included patients without
      thrombocytopenia before chemotherapy (to prevent CIT), patients with
      thrombocytopenia during chemotherapy (to prevent recurrence of CIT), and other
      patients during chemotherapy (uncertain whether CIT had happened). There was no
      evidence for a difference in the number of patients with at least one bleeding
      episode of any severity (RR 0.27, 95% CI 0.07 to 1.02; one trial, 75
      participants). There was no evidence for a difference in the number of patients
      with at least one severe/life-threatening bleeding episode (RR 0.44, 95% CI 0.03
      to 6.77; one trial, 75 participants). This study did not address overall survival
      or quality of life. AUTHORS' CONCLUSIONS: No certain conclusions can be drawn due
      to the lack of strong evidence in the review. The available weak evidence did not
      support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in
      patients with solid tumours. There was no evidence to support the use of TPO-RAs
      for treating CIT in patients with solid tumours.

PMID- 29178134
TI  - Vector velocity imaging echocardiography to study the effects of submassive
      pulmonary embolism on the right atrium.
AB  - OBJECTIVES: To assess the effects of submassive pulmonary embolism (SMPE) on
      right atrial (RA) anatomy and function. BACKGROUND: Right ventricular dysfunction
      (RVD) is associated with adverse outcomes in SMPE. However, the effects of SMPE
      on the structure and function of the RA have received much less attention.
      METHODS: Fifty patients with SMPE documented by CT angiography (SMPE group) and
      evidence of RVD on two-dimensional echocardiography were retrospectively
      identified and compared to 50 controls (control group). Both RA and RV areas,
      volumes and fractional area change (FAC) were measured. Pulmonary artery systolic
      pressures were estimated. RA and RV longitudinal strains were obtained using
      vector velocity imaging (VVI). RESULTS: Compared with controls, RA and RV FACs
      were significantly reduced and associated with higher chamber volumes in the SMPE
      group. Global longitudinal RA strain was reduced in the SMPE group (29% + 11% vs
      55% + 16%; P < .01), as was global RV longitudinal strain (-12% + 5% vs -20% +
      5%, P < .01), when compared to the controls. A linear relationship existed
      between RV and RA strain in both groups; however, the curve was shifted downward
      among those with SMPE. Furthermore, ROC curve analysis suggests RA area performs
      better than RV area as a marker of SMPE. CONCLUSIONS: RA structure and function
      are adversely affected in SMPE, similar to the effects observed in RV. Lower RA
      strain appears to be a novel quantitative indicator of SMPE, and RA area may be a
      more sensitive marker of this condition and may provide additional prognostic
      information in this condition.

PMID- 29178135
TI  - Demographically idiosyncratic responses to climate change and rapid Pleistocene
      diversification of the walnut genus Juglans (Juglandaceae) revealed by whole
      genome sequences.
AB  - Whether species demography and diversification are driven primarily by extrinsic
      environmental changes such as climatic oscillations in the Quaternary or by
      intrinsic biological interactions like coevolution between antagonists is a
      matter of active debate. In fact, their relative importance can be assessed by
      tracking past population fluctuations over considerable time periods. We applied
      the pairwise sequentially Markovian coalescent approach on the genomes of 11
      temperate Juglans species to estimate trajectories of changes in effective
      population size (Ne ) and used a Bayesian-coalescent based approach that
      simultaneously considers multiple genomes (G-PhoCS) to estimate divergence times
      between lineages. Ne curves of all study species converged 1.0 million yr ago,
      probably reflecting the time when the walnut genus last shared a common ancestor.
      This estimate was confirmed by the G-PhoCS estimates of divergence times. But all
      species did not react similarly to the dramatic climatic oscillations following
      early Pleistocene cooling, so the timing and amplitude of changes in Ne differed
      among species and even among conspecific lineages. The population histories of
      temperate walnut species were not driven by extrinsic environmental changes
      alone, and a key role was probably played by species-specific factors such as
      coevolutionary interactions with specialized pathogens.

PMID- 29178133
TI  - Variants with a low allele frequency detected in genomic DNA affect the accuracy
      of mutation detection in cell-free DNA by next-generation sequencing.
AB  - BACKGROUND: Next-generation sequencing of cell-free DNA (cfDNA) has been shown to
      be a useful noninvasive test for detecting mutations in solid tumors. METHODS:
      Targeted gene sequencing was performed with a panel of 263 cancer-related genes
      for cfDNA and genomic DNA of peripheral blood mononuclear cells (PBMCs) obtained
      from presurgical specimens of 6 lung cancer patients, and mutation calls in these
      samples were compared with those of primary tumors and corresponding patient
      derived xenografts (PDXs). RESULTS: Approximately 67% of the mutations detected
      in the tumor samples (primary tumors and/or PDXs) were also detected in genomic
      DNA from PBMCs as background mutations. These background mutations consisted of
      germline polymorphisms and a group of mutations with low allele frequencies,
      mostly <10%. These variants with a low allele frequency were repeatedly detected
      in all types of samples from the same patients and at similarly low allele
      frequency levels in PBMCs from different patients; this indicated that their
      detection might be derived from common causes, such as homologous sequences in
      the human genome. Allele frequencies of mutations detected in both primary tumors
      and cfDNA showed 2 patterns: 1) low allele frequencies (approximately 1%-10%) in
      cfDNA but high allele frequencies (usually >10% or >3-fold increase) in primary
      tumors and further enrichment in PDXs and 2) similar allele frequencies across
      samples. CONCLUSIONS: Because only a small fraction of total cfDNA might be
      derived from tumor cells, only mutations with the first allele frequency pattern
      may be regarded as tumor-specific mutations in cfDNA. Effective filtering of
      background mutations will be required to improve the accuracy of mutation calls
      in cfDNA. Cancer 2018;124:1061-9. (c) 2017 American Cancer Society.

PMID- 29178136
TI  - Case of pigmented lipofibromatosis in a 27-year-old woman.

PMID- 29178138
TI  - Two aortic valves in the parasternal long-axis view: Aortic dissection or
      artifact?
AB  - Refraction artifact produced the appearance of two aortic valves in the
      parasternal long axis view. Aortic dissection was ruled out by CT angiography.

PMID- 29178137
TI  - Continuous Automated Model EvaluatiOn (CAMEO) complementing the critical
      assessment of structure prediction in CASP12.
AB  - Every second year, the community experiment "Critical Assessment of Techniques
      for Structure Prediction" (CASP) is conducting an independent blind assessment of
      structure prediction methods, providing a framework for comparing the performance
      of different approaches and discussing the latest developments in the field. Yet,
      developers of automated computational modeling methods clearly benefit from more
      frequent evaluations based on larger sets of data. The "Continuous Automated
      Model EvaluatiOn (CAMEO)" platform complements the CASP experiment by conducting
      fully automated blind prediction assessments based on the weekly pre-release of
      sequences of those structures, which are going to be published in the next
      release of the PDB Protein Data Bank. CAMEO publishes weekly benchmarking results
      based on models collected during a 4-day prediction window, on average assessing
      ca. 100 targets during a time frame of 5 weeks. CAMEO benchmarking data is
      generated consistently for all participating methods at the same point in time,
      enabling developers to benchmark and cross-validate their method's performance,
      and directly refer to the benchmarking results in publications. In order to
      facilitate server development and promote shorter release cycles, CAMEO sends
      weekly email with submission statistics and low performance warnings. Many
      participants of CASP have successfully employed CAMEO when preparing their
      methods for upcoming community experiments. CAMEO offers a variety of scores to
      allow benchmarking diverse aspects of structure prediction methods. By
      introducing new scoring schemes, CAMEO facilitates new development in areas of
      active research, for example, modeling quaternary structure, complexes, or ligand
      binding sites.

PMID- 29178140
TI  - First Direct Evidence of Cue Integration in Reorientation: A New Paradigm.
AB  - There are several models of the use of geometric and feature cues in
      reorientation (Cheng, Huttenlocher, & Newcombe, ). The adaptive combination
      approach posits that people integrate cues with weights that depend on cue
      salience and learning, or, when discrepancies are large, they choose between cues
      based on these variables (Cheng, Shettleworth, Huttenlocher, & Rieser, ; Newcombe
      & Huttenlocher, ). In a new paradigm designed to evaluate integration and choice,
      disoriented participants attempted to return to a heading direction, in a
      trapezoidal enclosure in which feature and geometric cues both unambiguously
      specified a heading, but later the feature was moved. With discrepancies greater
      than 90 degrees, participants choose geometry. With smaller discrepancies,
      integration appeared in three of five situations; otherwise, participants used
      geometry alone. Variation depended on direction of feature movement and whether
      the nearest corner was acute or obtuse. The results have implications for
      contrasting adaptive combination and modularity theory, and for future research,
      offering a new paradigm for reorientation research, and for testing cue
      integration more broadly.

PMID- 29178139
TI  - Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in
      Alzheimer's disease.
AB  - Reactive astrogliosis, a complex process characterized by cell hypertrophy and
      upregulation of components of intermediate filaments, is a common feature in
      brains of Alzheimer's patients. Reactive astrocytes are found in close
      association with neuritic plaques; however, the precise role of these glial cells
      in disease pathogenesis is unknown. In this study, using immunohistochemical
      techniques and light and electron microscopy, we report that plaque-associated
      reactive astrocytes enwrap, engulf and may digest presynaptic dystrophies in the
      hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) mice. Microglia,
      the brain phagocytic population, was apparently not engaged in this clearance.
      Phagocytic reactive astrocytes were present in 35% and 67% of amyloid plaques at
      6 and 12 months of age, respectively. The proportion of engulfed dystrophic
      neurites was low, around 7% of total dystrophies around plaques at both ages.
      This fact, along with the accumulation of dystrophic neurites during disease
      course, suggests that the efficiency of the astrocyte phagocytic process might be
      limited or impaired. Reactive astrocytes surrounding and engulfing dystrophic
      neurites were also detected in the hippocampus of Alzheimer's patients by
      confocal and ultrastructural analysis. We posit that the phagocytic activity of
      reactive astrocytes might contribute to clear dysfunctional synapses or synaptic
      debris, thereby restoring impaired neural circuits and reducing the inflammatory
      impact of damaged neuronal parts and/or limiting the amyloid pathology.
      Therefore, potentiation of the phagocytic properties of reactive astrocytes may
      represent a potential therapy in Alzheimer's disease.

PMID- 29178141
TI  - Probing and Manipulating the Interfacial Defects of InGaAs Dual-Layer Metal
      Oxides at the Atomic Scale.
AB  - The interface between III-V and metal-oxide-semiconductor materials plays a
      central role in the operation of high-speed electronic devices, such as
      transistors and light-emitting diodes. The high-speed property gives the light
      emitting diodes a high response speed and low dark current, and they are widely
      used in communications, infrared remote sensing, optical detection, and other
      fields. The rational design of high-performance devices requires a detailed
      understanding of the electronic structure at this interface; however, this
      understanding remains a challenge, given the complex nature of surface
      interactions and the dynamic relationship between the morphology evolution and
      electronic structures. Herein, in situ transmission electron microscopy is used
      to probe and manipulate the structural and electrical properties of ZrO2 films on
      Al2 O3 and InGaAs substrate at the atomic scale. Interfacial defects resulting
      from the spillover of the oxygen-atom conduction-band wavefunctions are resolved.
      This study unearths the fundamental defect-driven interfacial electric structure
      of III-V semiconductor materials and paves the way to future high-speed and high
      reliability devices.

PMID- 29178142
TI  - Three-dimensional echocardiography to evaluate right atrial volume and phasic
      function in pulmonary hypertension.
AB  - OBJECTIVE: Pulmonary hypertension (PH) impairs right ventricular (RV) systolic
      and diastolic function, which in turn induces compensatory changes in right
      atrial (RA) function; the diverse effects on RA function are subject to much
      debate. We hypothesized that RA function plays a more important role in
      compensating RV dysfunction, than mere prevention of clinical failure in patients
      with PH. METHODS: We studied 54 patients with PH and 23 healthy controls. RA
      volume, including maximum RA volume, minimum RA volume, and the volume before
      atrial systole, was evaluated by 3DE. RA maximum volume index (Vmax I), total
      emptying volume index (TotEVI), passive emptying volume index (PassEVI), and
      active ejection fraction (ActEF) were calculated. Receiver operating
      characteristic curve analysis was used to determine the sensitivity and
      specificity of various cutoff levels of the variables measured for predicting
      World Health Organization functional class (WHO-FC) IV in patients with PH.
      RESULTS: RAVmax I in patients with PH was higher than that in controls. In
      patients with PH, the TotEVI was significantly higher, while PassEVI was
      significantly lower as compared to that in controls. ActEF was increased in
      patients with WHO functional class (WHO-FC) III PH as compared to that in
      controls (P = .003) but was reduced in more advanced cases (WHO-FC IV). In
      addition, the area under the curve of 3D RA ActEF was larger than those of 2D RA
      ActEF, RA GLS, RA area, FAC, TAPSE, and RIMP (P < .01 for all) for predicting WHO
      FC IV. CONCLUSION: We demonstrated that RA function plays a more important role
      in compensating RV dysfunction then mere prevention of clinical failure in PH.

PMID- 29178143
TI  - Peptide modulators of Rac1/Tiam1 protein-protein interaction: An alternative
      approach for cardiovascular diseases.
AB  - Rac1 GTPase interaction with guanine nucleotide exchange factor Tiam1 is involved
      in several cancer types and cardiovascular diseases. Although small molecules
      interfering with their protein-protein interaction (PPI) were identified and
      studied, the ability of small peptides and peptide mimics acting as Rac1/Tiam1
      PPI inhibitors has not been yet explored. Using computational alanine scanning
      (CAS), the "hot" interfacial residues have been determined allowing the design of
      a small library of putative PPI inhibitors. In particular, the insertion of an
      unnatural alpha, alpha disubstituted amino acid, that is norbornane amino acid,
      and the side chain stapling have been evaluated regarding both conformational
      stability and biological activity. REMD calculations and CD studies have
      indicated that one single norbornane amino acid at the N-terminus is not
      sufficient to stabilize the helix structure, while the side-chain stapling is a
      more efficient strategy. Furthermore, both engineered peptides have been found
      able to reduce Rac1-GTP levels in cultured human smooth muscle cells, while wild
      type sequence is not active.

PMID- 29178144
TI  - Outcome measures in Duchenne muscular dystrophy: sensitivity to change, clinical
      meaningfulness, and implications for clinical trials.

PMID- 29178145
TI  - Comparative epigenomics reveals evolution of duplicated genes in potato and
      tomato.
AB  - The evolution of duplicated genes after polyploidization has been the subject of
      many evolutionary biology studies. Potato (Solanum tuberosum) and tomato (Solanum
      lycopersicum) are the first two sequenced genomes of asterids, and share a common
      polyploidization event. However, the epigenetic role of DNA methylation on the
      evolution of duplicated genes derived from polyploidization is not fully
      understood. Here, we explore the role of the DNA methylation in the evolution of
      duplicated genes in potato and tomato. The overall levels of DNA methylation are
      different, although patterns of DNA methylation are similar in potato and tomato.
      Different types of duplicated genes can display different methylation patterns in
      potato and tomato. In addition, we found that differences in the methylation
      levels between duplicated genes were associated with gene expression divergence.
      In particular, for the majority of duplicated gene pairs, one copy is always
      hyper- or hypo-methylated compared with the other copy across different tomato
      fruit ripening stages, and these genes are enriched for specific function related
      to transcription factor (TF) activity. Furthermore, transcription of hundreds of
      duplicated TFs was shown to be regulated by DNA methylation during fruit ripening
      stages in tomato, some of which are well-known fruit ripening TFs. Taken
      together, our results support the notion that DNA methylation may facilitate
      divergent evolution of duplicated genes and play roles in important biological
      processes such as tomato fruit ripening.

PMID- 29178146
TI  - BRAF mutations might be more common than supposed in vulvar melanomas.
AB  - Data on BRAF, NRAS and KIT mutations are scarce in patients with vulvo-vaginal
      melanomas and are associated with important therapeutic issues. We investigated
      their prevalence in a cohort of patients with female lower genital tract
      melanomas between 2003 and 2017. Of the 22 patients, 5 (22.7%) harboured a BRAF
      mutation, which was much higher than the rate of 5% reported in the literature.
      One patient, who was tested negative on the primary melanoma, had a NRAS mutation
      in a cutaneous metastasis. Our data provide a rationale for prospective and
      repeated mutations testing in female lower genital tract melanomas.

PMID- 29178147
TI  - Psychosocial predictors of distress and depression among South African breast
      cancer patients.
AB  - OBJECTIVE: The present study focused on psychological distress and symptoms of
      depression among a sample of patients attending an outpatient breast cancer
      clinic in South Africa. The authors also sought to identify the predictors of
      distress and depression by using demographic, medical, and psychosocial
      variables, including perceived and received social support. METHODS: A
      convenience sample of breast cancer patients was recruited from the Breast Clinic
      at a hospital in the Western Cape, South Africa. Participants (N = 201) were
      asked to complete a questionnaire battery consisting of, inter alia, the Center
      for Epidemiological Studies-Depression Scale, the Hopkins Symptom Checklist, and
      the Berlin Social Support Scales. RESULTS: More than one-third of participants
      scored in the elevated ranges on the Center for Epidemiological Studies
      Depression Scale and Hopkins Symptom Checklist, indicating that distress and
      symptoms of depression were a concern for a sizable minority of participants.
      Regression analysis showed that body change stress and perceived social support
      were significant predictors of both psychological distress and symptoms of
      depression. CONCLUSIONS: Distress and depressive symptoms are prevalent among
      South African breast cancer patients, especially those with higher body change
      stress and lower perceived support. For breast cancer patients who are distressed
      or have symptoms of depression, social support, information, psychosocial
      counseling, and in some cases, referral for medication management and cognitive
      psychotherapy is indicated. This article calls attention to the need for
      psychosocial services directed at supporting patients receiving care at breast
      clinics in South Africa.

PMID- 29178148
TI  - Confined Synthesis of Carbon Nitride in a Layered Host Matrix with Unprecedented
      Solid-State Quantum Yield and Stability.
AB  - Fluorescent carbon nanomaterials have drawn tremendous attention for their
      intriguing optical performances, but their employment in solid-state luminescent
      devices is rather limited as a result of aggregation-induced photoluminescence
      quenching. Herein, ultrathin carbon nitride (CN) is synthesized within the 2D
      confined region of layered double hydroxide (LDH) via triggering the interlayer
      condensation reaction of citric acid and urea. The resulting CN/LDH phosphor
      emits strong cyan light under UV-light irradiation with an absolute solid-state
      quantum yield (SSQY) of 95.9 +/- 2.2%, which is, to the best of our knowledge,
      the highest value of carbon-based fluorescent materials ever reported.
      Furthermore, it exhibits a strong luminescence stability toward temperature,
      environmental pH, and photocorrosion. Both experimental studies and theoretical
      calculations reveal that the host-guest interactions between the rigid LDH matrix
      and interlayer carbon nitride give the predominant contribution to the
      unprecedented SSQY and stability. In addition, prospective applications of the
      CN/LDH material are demonstrated in both white light-emitting diodes and
      upconversion fluorescence imaging of cancer cells.

PMID- 29178149
TI  - Measuring activities and participation in persons with haemophilia: A systematic
      review of commonly used instruments.
AB  - INTRODUCTION: Monitoring clinical outcome in persons with haemophilia (PWH) is
      essential in order to provide optimal treatment for individual patients and
      compare effectiveness of treatment strategies. Experience with measurement of
      activities and participation in haemophilia is limited and consensus on preferred
      tools is lacking. AIM: The aim of this study was to give a comprehensive overview
      of the measurement properties of a selection of commonly used tools developed to
      assess activities and participation in PWH. METHODS: Electronic databases were
      searched for articles that reported on reliability, validity or responsiveness of
      predetermined measurement tools (5 self-reported and 4 performance based
      measurement tools). Methodological quality of the studies was assessed according
      to the COSMIN checklist. Best evidence synthesis was used to summarize evidence
      on the measurement properties. RESULTS: The search resulted in 3453 unique hits.
      Forty-two articles were included. The self-reported Haemophilia Acitivity List
      (HAL), Pediatric HAL (PedHAL) and the performance based Functional Independence
      Score in Haemophilia (FISH) were studied most extensively. Methodological quality
      of the studies was limited. Measurement error, cross-cultural validity and
      responsiveness have been insufficiently evaluated. CONCLUSION: Albeit based on
      limited evidence, the measurement properties of the PedHAL, HAL and FISH are
      currently considered most satisfactory. Further research needs to focus on
      measurement error, responsiveness, interpretability and cross-cultural validity
      of the self-reported tools and validity of performance based tools which are able
      to assess limitations in sports and leisure activities.

PMID- 29178150
TI  - Towards a Kieselguhr- and PVPP-Free Clarification and Stabilization Process of
      Rough Beer at Room-Temperature Conditions.
AB  - : In this work, the main constraint (that is, beer chilling and chill haze
      removing) of the current beer conditioning techniques using Kieselguhr filtration
      and Polyvinylpolypyrrolidone (PVPP) treatment was overcome by developing a novel
      higher-throughput conditioning process, operating at room temperatures with no
      use of filter aids. The effect of filtration temperature (TF ) in the range of 0
      to 40  degrees C on the hydraulic permeability of ceramic hollow-fiber (HF)
      membranes with nominal pore size of 0.2 to 1.4 MUm, as well as on their limiting
      permeation flux (J* ) when feeding precentrifuged rough beer, was preliminarily
      assessed. When using the 1.4-MUm HF membrane operating at TF >= 20  degrees C, it
      was possible to enhance the average permeation flux at values (676 to 1844 L/m2
      /h), noticeably higher than those (250 to 500 L/m2 /h) characteristics of
      conventional powder filtration. Despite its acceptable permanent haze, the
      resulting beer permeate still exhibited colloidal instability. By resorting to
      the commercial enzyme preparation Brewers Clarex(r) before beer clarification, it
      was possible to significantly improve its colloidal stability as measured using a
      number of European Brewing Convention forcing tests, especially with respect to
      that of precentrifuged rough beer by itself. By combining the above enzymatic
      treatment with membrane clarification at 30  degrees C across the ceramic 1.4-MUm
      HF membrane module, it was possible to limit the haze development due to
      chilling, sensitive proteins, and alcohol addition to as low as 0.78, 4.1, and
      4.0 EBC-U, respectively, the enzymatic treatment being by far more effective than
      that using PVPP. PRACTICAL APPLICATION: A novel Kieselguhr- and PVPP-free rough
      beer conditioning process at room temperatures was set up. By submitting
      precentrifuged rough beer to commercial preparation Brewers Clarex (r) and then
      to membrane clarification at 30  degrees C across a ceramic 1.4-MUm hollow-fiber
      membrane module, it was possible to obtain a clear and stable beer with a
      throughput (1306 +/- 72 L/m2 /h) by far higher than that (250 to 500 L/m2 /h)
      characterizing the current powder filters. The haze development due to chilling,
      sensitive proteins, and alcohol adding was by far lower than that observed when
      microfiltering PVPP-pretreated rough beer.

PMID- 29178151
TI  - A Metal-Organic-Framework-Based Electrolyte with Nanowetted Interfaces for High
      Energy-Density Solid-State Lithium Battery.
AB  - Solid-state batteries (SSBs) are promising for safer energy storage, but their
      active loading and energy density have been limited by large interfacial
      impedance caused by the poor Li+ transport kinetics between the solid-state
      electrolyte and the electrode materials. To address the interfacial issue and
      achieve higher energy density, herein, a novel solid-like electrolyte (SLE) based
      on ionic-liquid-impregnated metal-organic framework nanocrystals (Li-IL@MOF) is
      reported, which demonstrates excellent electrochemical properties, including a
      high room-temperature ionic conductivity of 3.0 * 10-4 S cm-1 , an improved Li+
      transference number of 0.36, and good compatibilities against both Li metal and
      active electrodes with low interfacial resistances. The Li-IL@MOF SLE is further
      integrated into a rechargeable Li|LiFePO4 SSB with an unprecedented active
      loading of 25 mg cm-2 , and the battery exhibits remarkable performance over a
      wide temperature range from -20 up to 150  degrees C. Besides the intrinsically
      high ionic conductivity of Li-IL@MOF, the unique interfacial contact between the
      SLE and the active electrodes owing to an interfacial wettability effect of the
      nanoconfined Li-IL guests, which creates an effective 3D Li+ conductive network
      throughout the whole battery, is considered to be the key factor for the
      excellent performance of the SSB.

PMID- 29178152
TI  - Identification, characterization and distribution of terpene indole alkaloids in
      ethanolic extracts of Catharanthus roseus using high-performance liquid
      chromatography/electrospray ionization quadrupole time-of-flight tandem mass
      spectrometry and the study of their geographical variation.
AB  - RATIONALE: Catharanthus roseus is a well-known dicotyledonous medicinal plant
      containing diverse classes of bioactive terpene indole alkaloids (TIAs), in
      particular the anticancer agents vinblastine and vincristine. In view of the
      commercial importance of these compounds there is an urgent need to develop an
      accurate and reliable method for the screening of TIAs from C. roseus. METHODS: A
      method for the separation and characterization of these compounds was developed
      using high-performance liquid chromatography coupled with positive electrospray
      ionization quadrupole time-of-flight tandem mass spectrometry (HPLC/ESI-QTOF
      MS/MS). Chromatographic separation of TIAs was carried out using a Thermo Betasil
      C8 column (250 mm * 4.5 mm, 5 MUm) at 25 degrees C using 0.1% formic acid in
      water and acetonitrile. RESULTS: Diagnostic fragmentation pathways for
      vinpocetine, vindesine, catharanthine, vinblastine, vindoline and vincristine
      were established on the basis of their product ions. A total of 72 TIAs were
      detected of which 11 were unambiguously identified by comparison with their
      standards, and the remaining 61 were tentatively identified. The geographical
      distribution of the TIAs in ethanolic extracts of 30 samples of C. roseus
      collected from five states of India was studied using principal component
      analysis (PCA). CONCLUSIONS: The developed analytical method together with
      diagnostic fragment patterns were used to rapidly and effectively identify
      targeted and untargeted TIAs in C. roseus. A PCA study of the results obtained
      was used to discriminate among the C. roseus samples.

PMID- 29178153
TI  - Global transition of human serum albumin to prefibrillar aggregates induced by
      temsirolimus: Insight into implications of anti-renal cancer drug.
AB  - In our study, we have characterized the prefibrillar aggregates of human serum
      albumin (HSA) induced by temsirolimus, anti-renal cancer drug. Molecular docking
      was retorted to confirm binding of HSA and temsirolimus. Temsirolimus caused the
      structural transition of native HSA to non-native species after prolonged
      incubation of 20 days. These non-native species were characterized as
      prefibrillar aggregates as evident by decreased intrinsic fluorescence and
      enhanced 8-anilino-1-naphthalene-sulphonic acid (ANS) fluorescence. Further,
      enhanced thioflavin T fluorescence and shift in congo red (CR) spectra of
      temsirolimus-incubated HSA as compared to native HSA are suggestive of global
      transition of HSA in presence of temsirolimus towards prefibrillar aggregates.
      Circular dichroism spectroscopy revealed alpha to beta transition upon prolonged
      incubation with temsirolimus suggesting the formation of prefibrillar aggregates
      as aggregates are known to possess high beta content. Scanning electron
      microscopy confirmed these non-native species to be prefibrillar aggregates
      evident by observed sheath-like structures. Comet assay was retorted to confirm
      genotoxic nature of these prefibrillar aggregates; DNA damage was observed for
      temsirolimus-incubated HSA confirming the genotoxic nature of prefibrillar
      aggregates. These prefibrillar aggregates are observed at heart of many
      pathological conditions, thus making our study clinically significant.

PMID- 29178154
TI  - Ion-Solvent Complexes Promote Gas Evolution from Electrolytes on a Sodium Metal
      Anode.
AB  - Lithium and sodium metal batteries are considered as promising next-generation
      energy storage devices due to their ultrahigh energy densities. The high
      reactivity of alkali metal toward organic solvents and salts results in side
      reactions, which further lead to undesirable electrolyte depletion, cell failure,
      and evolution of flammable gas. Herein, first-principles calculations and in situ
      optical microscopy are used to study the mechanism of organic electrolyte
      decomposition and gas evolution on a sodium metal anode. Once complexed with
      sodium ions, solvent molecules show a reduced LUMO, which facilitates the
      electrolyte decomposition and gas evolution. Such a general mechanism is also
      applicable to lithium and other metal anodes. We uncover the critical role of ion
      solvent complexation for the stability of alkali metal anodes, reveal the
      mechanism of electrolyte gassing, and provide a mechanistic guidance to
      electrolyte and lithium/sodium anode design for safe rechargeable batteries.

PMID- 29178155
TI  - Correction for Burbrink and Pyron (2011).

PMID- 29178156
TI  - Correction for Palmer and Feldman (2011).

PMID- 29178157
TI  - Correction for Maughan 2007.

PMID- 29178158
TI  - Pre-exposure prophylaxis: awareness, acceptability and risk compensation
      behaviour among men who have sex with men and the transgender population.
AB  - OBJECTIVES: This exploratory study examined the facilitators of and barriers to
      acceptance of pre-exposure prophylaxis (PrEP) and potential risk compensation
      behaviour emerging from its use among men who have sex with men (MSM) and
      transgender individuals (TGs) in India. METHODS: A questionnaire was administered
      to 400 individuals registered with a targeted intervention programme. Logistic
      regression models were used to identify facilitators of and barriers to PrEP
      acceptance. RESULTS: The respondents consisted of 68% MSM and 32% TGs. Risk
      behaviour categorization identified 40% as low risk, 41% as medium risk and, 19%
      as high risk for HIV infection. About 93% of the respondents were unaware of
      PrEP, but once informed about it, 99% were willing to use PrEP. The facilitators
      of PrEP acceptance were some schooling [odds ratio (OR) 2.16; P = 0.51], being
      married or in a live-in relationship (OR 2.08; P = 0.46), having a high
      calculated risk (OR 3.12; P = 0.33), and having a high self-perceived risk (OR
      1.8; P = 0.35). Increasing age (OR 2.12; P = 0.04) was a significant barrier. TGs
      had higher odds of acceptance of PrEP under conditions of additional cost (OR
      2.12; P = 0.02) and once-daily pill (OR 2.85; P = 0.04). Individuals identified
      as low risk for HIV infection showed lower odds of potential risk compensation,
      defined as more sexual partners (OR 0.8; P = 0.35), unsafe sex with new partners
      (OR 0.71; P = 0.16), and decreased condom use with regular partners (OR 0.95; P =
      0.84), as compared with medium-risk individuals. The associations, although not
      statistically significant, are nevertheless important for public health action
      given the limited scientific evidence on PrEP use among MSM and TGs in India.
      CONCLUSIONS: With high acceptability and a low likelihood of risk compensation
      behaviour, PrEP can be considered as an effective prevention strategy for HIV
      infection among MSM and TGs in India.

PMID- 29178159
TI  - Crystallographic insights into the self-assembly of KLVFF amyloid-beta peptides.
AB  - Amyloidogenic peptide fragment KLVFF (H2 N-Lys-Leu-Val-Phe-Phe-COOH, Abeta16-20
      ), the core-sequence of the polypeptide Abeta40, is a well-studied model for
      amyloid formation. However, due to its low crystallinity, detailed atomic
      information of KLVFF structure is lacking. Here we report the high-resolution
      single-crystal X-ray structure of two monohalogenated KLVFF derivatives, KLVFF(I)
      and KLVFF(Br). The obtained results highlight how halogenation is a good strategy
      to promote crystallization and facilitate the phase determination of KLVFF(I) and
      KLVFF(Br) fragments. Detailed structural studies on the packing features of both
      monohalogenated derivatives reveal the role of the halogen atoms showing that
      when they are positioned on the Phe aromatic moiety at the C-terminus they do not
      form halogen bonds and thus do not produce any extra stabilization of the beta
      sheet in the self-assembly process. The structural evidences gained from these
      studies corroborate the various polymorphic nanostructures of the halogenated
      variants of KLVFF and confirm the possibility to use halogenation as innovative
      strategy to tune the morphology of this pentapeptide.

PMID- 29178160
TI  - Results of multilevel surgery in diplegic cerebral palsy at skeletal maturity:
      new evidence.

PMID- 29178163
TI  - Obituary: Michel Jouvet (1925-2017), The father of paradoxical sleep.

PMID- 29178161
TI  - Analytical dose modeling for preclinical proton irradiation of millimetric
      targets.
AB  - PURPOSE: Due to the considerable development of proton radiotherapy, several
      proton platforms have emerged to irradiate small animals in order to study the
      biological effectiveness of proton radiation. A dedicated analytical treatment
      planning tool was developed in this study to accurately calculate the delivered
      dose given the specific constraints imposed by the small dimensions of the
      irradiated areas. METHODS: The treatment planning system (TPS) developed in this
      study is based on an analytical formulation of the Bragg peak and uses
      experimental range values of protons. The method was validated after comparison
      with experimental data from the literature and then compared to Monte Carlo
      simulations conducted using Geant4. Three examples of treatment planning,
      performed with phantoms made of water targets and bone-slab insert, were
      generated with the analytical formulation and Geant4. Each treatment planning was
      evaluated using dose-volume histograms and gamma index maps. RESULTS: We
      demonstrate the value of the analytical function for mouse irradiation, which
      requires a targeting accuracy of 0.1 mm. Using the appropriate database, the
      analytical modeling limits the errors caused by misestimating the stopping power.
      For example, 99% of a 1-mm tumor irradiated with a 24-MeV beam receives the
      prescribed dose. The analytical dose deviations from the prescribed dose remain
      within the dose tolerances stated by report 62 of the International Commission on
      Radiation Units and Measurements for all tested configurations. In addition, the
      gamma index maps show that the highly constrained targeting accuracy of 0.1 mm
      for mouse irradiation leads to a significant disagreement between Geant4 and the
      reference. This simulated treatment planning is nevertheless compatible with a
      targeting accuracy exceeding 0.2 mm, corresponding to rat and rabbit
      irradiations. CONCLUSION: Good dose accuracy for millimetric tumors is achieved
      with the analytical calculation used in this work. These volume sizes are typical
      in mouse models for radiation studies. Our results demonstrate that the choice of
      analytical rather than simulated treatment planning depends on the animal model
      under consideration.

PMID- 29178164
TI  - Issues and challenges in implementing clinical practice guideline for the
      management of chronic insomnia.

PMID- 29178165
TI  - Outcomes of cellophane banding or percutaneous transvenous coil embolization of
      canine intrahepatic portosystemic shunts.
AB  - OBJECTIVE: To compare clinical outcomes of dogs with congenital intrahepatic
      portosystemic shunts (CIHPSS) treated with cellophane banding (CB) or
      percutaneous transvenous coil embolization (PTCE). STUDY DESIGN: Dual
      institutional retrospective study. ANIMALS: Fifty-eight dogs with CIHPSS (2001
      2016). METHODS: Medical records of dogs undergoing CB or PTCE for CIHPSS were
      reviewed for signalment, body weight, hematologic values, shunt location,
      attenuation technique, procedure time, duration of hospitalization,
      complications, date of follow-up, and cause of death if applicable. RESULTS:
      Thirty-one dogs underwent CB, and 27 dogs underwent PTCE. No differences were
      detected between groups for gender, preoperative packed cell volume, albumin,
      cholesterol, or bile acids. Body weight was greater in dogs treated via PTCE.
      Shunts differed in location because dogs undergoing CB were diagnosed with more
      left divisional shunts compared with PTCE dogs. Procedural duration of CB and
      PTCE did not differ. Dogs treated with CB sustained more minor postoperative
      complications and were hospitalized longer than dogs treated with PTCE. The 1
      year and 2-year survival rates were 89% for the CB group and 87% and 80% for the
      PTCE group, respectively. The proportion surviving at 5 years was 75% and 80% for
      CB dogs and PTCE dogs, respectively. CONCLUSION: CB and PTCE are associated with
      similar short-term and intermediate-term survival. PTCE is a minimally invasive
      alternative to CB via celiotomy. However, CB allows concurrent abdominal
      procedures requiring the same approach.

PMID- 29178166
TI  - Efficacy of irrigant activation techniques in removing intracanal smear layer and
      debris from mature permanent teeth: a systematic review and meta-analysis.
AB  - AIMS: To establish whether irrigant activation techniques (IATs) result in
      greater intracanal smear layer and debris removal than conventional needle
      irrigation (CNI). METHODOLOGY: Six electronic databases were searched to identify
      scanning electron microscopy studies evaluating smear layer and/or debris removal
      following the use of manual dynamic activation (MDA), passive ultrasonic
      irrigation (PUI), sonic irrigation (SI) or apical negative pressure (ANP) IATs in
      mature permanent teeth. Meta-analyses were performed for each canal segment
      (coronal, middle, apical and apical 1 mm) in addition to subgroup analyses for
      individual IATs with respect to CNI. Outcomes were presented as standardized mean
      differences (SMD) alongside 95% confidence intervals (95% CI) and chi-squared
      analysis. RESULTS: From 252 citations, 16 studies were identified. The meta
      analyses demonstrated significant improvements in coronal (SMD: 1.15, 95% CI:
      0.72-1.57 / SMD: 0.54, 95% CI: 0.29-0.80), middle (SMD: 1.30, 95% CI: 0.59-2.53 /
      SMD: 0.8, 95% CI: 0.58-1.13) and apical thirds (SMD: 1.22, 95% CI: 0.83-1.62 /
      SMD: 1.86, 95% CI: 0.76-2.96) for smear layer and debris removal, respectively.
      In the apical 1 mm IATs improved cleanliness; however, differences were
      insignificant (SMD: 1.15, 95% CI: -0.47-2.77). Chi-squared analysis revealed
      heterogeneity scores of 79.3-92.8% and 0.0-93.5% for smear layer and debris
      removal, respectively. CONCLUSIONS: IATs improve intracanal cleanliness across a
      substantial portion of the canal, and therefore, their use is recommended
      throughout root canal preparation. However, current data is too heterogeneous to
      compare and identify superiority of an individual technique highlighting the need
      to standardize experimental protocols and develop a more representative research
      model to investigate the in vivo impact of IATs on clinical outcomes and
      periapical healing following root canal treatment.

PMID- 29178167
TI  - Interfacial Interactions in Monolayer and Few-Layer SnS/CH3 NH3 PbI3 Perovskite
      van der Waals Heterostructures and Their Effects on Electronic and Optical
      Properties.
AB  - A high light-absorption coefficient and long-range hot-carrier transport of
      hybrid organic-inorganic perovskites give huge potential to their composites in
      solar energy conversion and environmental protection. Understanding interfacial
      interactions and their effects are paramount for designing perovskite-based
      heterostructures with desirable properties. Herein, we systematically
      investigated the interfacial interactions in monolayer and few-layer SnS/CH3 NH3
      PbI3 heterostructures and their effects on the electronic and optical properties
      of these structures by density functional theory. It was found that the
      interfacial interactions in SnS/CH3 NH3 PbI3 heterostructures were van der Waals
      (vdW) interactions, and they were found to be insensitive to the layer number of
      2D SnS sheets. Interestingly, although their band gap decreased upon increasing
      the layer number of SnS, the near-gap electronic states and optical absorption
      spectra of these heterostructures were found to be strikingly similar. This
      feature was determined to be critical for the design of 2D layered SnS-based
      heterostructures. Strong absorption in the ultraviolet and visible-light regions,
      type II staggered band alignment at the interface, and few-layer SnS as an active
      co-catalyst make 2D SnS/CH3 NH3 PbI3 heterostructures promising candidates for
      photocatalysis, photodetectors, and solar energy harvesting and conversion. These
      results provide first insight into the nature of interfacial interactions and are
      useful for designing hybrid organic-inorganic perovskite-based devices with novel
      properties.

PMID- 29178168
TI  - Core information set for informed consent to surgery for oral or oropharyngeal
      cancer: A mixed-methods study.
AB  - OBJECTIVES: To develop a core information set for informed consent to surgery for
      oral/oropharyngeal surgery. A core information set is baseline information rated
      important by patients and surgeons and is intended to improve patients'
      understanding of the intended procedure. DESIGN: A mixed-methods study.
      Systematic reviews of scientific and written healthcare literature, qualitative
      interviews and observations, Delphi surveys, and group consensus meetings
      identified information domains of importance for consent. SETTING: A regional
      head and neck clinic in the United Kingdom. Questionnaire participants were
      recruited from around the UK. PARTICIPANTS: Patients about to undergo, or who had
      previously undergone, surgery for oral/oropharyngeal cancer. Healthcare
      professionals involved in the management of head and neck cancer. MAIN OUTCOME
      MEASURES: The main outcome was a core information set. RESULTS: Systematic
      reviews, interviews and consultation observations yielded 887 pieces of
      information that were categorised into 87 information domains. Survey response
      rates were 67% (n = 50) and 71% (n = 52) for patient and healthcare professional
      groups in round one. More than 90% responded in each group in the second round.
      Healthcare professionals were more likely to rate information about short-term or
      peri-operative events as important while patients rated longer term issues about
      survival and quality of life. The consensus-building process resulted in an
      agreed core information set of 13 domains plus two procedure-specific domains
      about tracheostomy and free-flap surgery. CONCLUSION: This study produced a core
      information set for surgeons and patients to discuss before surgery for
      oral/oropharyngeal cancer. Future work will optimise ways to integrate core
      information into routine consultations.

PMID- 29178169
TI  - Authentication of commercial spices based on the similarities between gas
      chromatographic fingerprints.
AB  - BACKGROUND: A simple and solvent-free method was developed for the authentication
      of commercial spices. The similarities between gas chromatographic fingerprints
      were measured using similarity indices and multivariate data analyses, as
      morphological differentiation between dried powders and small spice particles was
      challenging. The volatile compounds present in 11 spices (i.e. allspice, anise,
      black pepper, caraway, clove, coriander, cumin, dill, fennel, star anise, and
      white pepper) were extracted by headspace solid-phase microextraction, and
      analysed by gas chromatography-mass spectrometry. RESULTS: The largest 10 peaks
      were selected from each total ion chromatogram, and a total of 65 volatiles were
      tentatively identified. The similarity indices (i.e. the congruence coefficients)
      were calculated using the data matrices of the identified compound relative peak
      areas to differentiate between two sets of fingerprints. Where pairs of similar
      fingerprints produced high congruence coefficients (>0.80), distinctive volatile
      markers were employed to distinguish between these samples. In addition,
      hierarchical cluster analysis and principal component analysis were performed to
      visualise the similarity among fingerprints, and the analysed spices were grouped
      and characterised according to their distinctive major components. CONCLUSION:
      This method is suitable for screening unknown spices, and can therefore be
      employed to evaluate the quality and authenticity of various spices. (c) 2017
      Society of Chemical Industry.

PMID- 29178170
TI  - The Decline of Basic Science Publications in Major Emergency Medicine Journals
      and Research Conferences.

PMID- 29178171
TI  - Effect of life-course family income trajectories on periodontitis: Birth cohort
      study.
AB  - AIMS: To quantify the impact of life course income trajectories on periodontitis
      in adulthood. MATERIALS AND METHODS: Data from the 1982 Pelotas Birth Cohort
      Study, Brazil, were used. Information on family income was collected at birth and
      ages 15, 19, 23 and 30 years. Group-based trajectory modelling was used to
      identify income trajectories. Periodontal measures were assessed through clinical
      examination at age 31. Log-Poisson regression models were used to estimate
      prevalence ratios (PRs) of any and moderate/severe periodontitis, as outcomes.
      RESULTS: Prevalence of any periodontitis and moderate/severe periodontitis was
      37.3% and 14.3% (n = 539). Income trajectories were associated with prevalence of
      moderate/severe periodontitis. Adjusted PR in participants in low and variable
      income trajectory was 2.1 times higher than in participants in stable high-income
      trajectory. The unadjusted association between income trajectories and prevalence
      of any periodontitis was explained by the inclusion of behavioural and clinical
      variables in the model. CONCLUSIONS: Low and variable life course income
      increased the prevalence of moderate/severe periodontitis at age 31 years. The
      findings may inform programmes in identifying and targeting potentially at-risk
      groups during the life course to prevent periodontitis.

PMID- 29178172
TI  - Anti-adhesion therapy following operative hysteroscopy for treatment of female
      subfertility.
AB  - BACKGROUND: Observational evidence suggests a potential benefit with several anti
      adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of
      an intrauterine device or balloon, hormonal treatment, barrier gels or human
      amniotic membrane grafting) for decreasing intrauterine adhesions (IUAs).
      OBJECTIVES: To assess the effectiveness of anti-adhesion therapies versus
      placebo, no treatment or any other anti-adhesion therapy, following operative
      hysteroscopy for treatment of female subfertility. SEARCH METHODS: We searched
      the following databases from inception to June 2017: the Cochrane Gynaecology and
      Fertility Group Specialised Register; the Cochrane Central Register of Studies
      (CRSO); MEDLINE; Embase; CINAHL and other electronic sources of trials, including
      trial registers, sources of unpublished literature and reference lists. We
      handsearched the Journal of Minimally Invasive Gynecology, and we contacted
      experts in the field. We also searched reference lists of appropriate papers.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) of anti-adhesion
      therapies versus placebo, no treatment or any other anti-adhesion therapy
      following operative hysteroscopy in subfertile women. The primary outcome was
      live birth. Secondary outcomes were clinical pregnancy, miscarriage and IUAs
      present at second-look hysteroscopy, along with mean adhesion scores and severity
      of IUAs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected
      studies, assessed risk of bias, extracted data and evaluated quality of evidence
      using the GRADE method. MAIN RESULTS: The overall quality of the evidence was low
      to very low. The main limitations were serious risk of bias related to blinding
      of participants and personnel, indirectness and imprecision. We identified 16
      RCTs comparing a device versus no treatment (two studies; 90 women), hormonal
      treatment versus no treatment or placebo (two studies; 136 women), device
      combined with hormonal treatment versus no treatment (one study; 20 women),
      barrier gel versus no treatment (five studies; 464 women), device with graft
      versus device without graft (three studies; 190 women), one type of device versus
      another device (one study; 201 women), gel combined with hormonal treatment and
      antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and
      device combined with gel versus device (one study; 120 women). The total number
      of participants was 1273, but data on 1133 women were available for analysis.
      Only two of 16 studies included 100% infertile women; in all other studies, the
      proportion was variable or unknown.No study reported live birth, but some (five
      studies) reported outcomes that were used as surrogate outcomes for live birth
      (term delivery or ongoing pregnancy). Anti-adhesion therapy versus placebo or no
      treatment following operative hysteroscopy.There was insufficient evidence to
      determine whether there was a difference between the use of a device or hormonal
      treatment compared to no treatment or placebo with respect to term delivery or
      ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42
      to 2.12; 107 women; 2 studies; I2 = 0%; very-low-quality evidence).There were
      fewer IUAs at second-look hysteroscopy using a device with or without hormonal
      treatment or hormonal treatment or barrier gels compared with no treatment or
      placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I2 = 0%; low-quality
      evidence). The number needed to treat for an additional beneficial outcome (NNTB)
      was 9 (95% CI 5 to 17). Comparisons of different anti-adhesion therapies
      following operative hysteroscopyIt was unclear whether there was a difference
      between the use of a device combined with graft versus device only for the
      outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies;
      I2 = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy
      using a device with or without graft/gel or gel combined with hormonal treatment
      and antibiotics compared with using a device only or hormonal treatment combined
      with antibiotics, but the findings of this meta-analysis were affected by
      evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I2 = 0%;
      low-quality evidence). AUTHORS' CONCLUSIONS: Implications for clinical
      practiceThe quality of the evidence ranged from very low to low. The
      effectiveness of anti-adhesion treatment for improving key reproductive outcomes
      or for decreasing IUAs following operative hysteroscopy in subfertile women
      remains uncertain. Implications for researchMore research is needed to assess the
      comparative safety and (cost-)effectiveness of different anti-adhesion treatments
      compared to no treatment or other interventions for improving key reproductive
      outcomes in subfertile women.

PMID- 29178173
TI  - Evaluation of apical transportation and centring ability of five thermally
      treated NiTi rotary systems.
AB  - AIM: To evaluate apical transportation and centring ability during root canal
      preparation in mesial root canals of mandibular molars associated with ProTaper
      Gold (PTG), ProDesign S (PDS), Hyflex CM (HCM), Hyflex EDM and ProDesign Logic
      (PDL). METHODOLOGY: Sixty mandibular first molars with two separate canals in the
      mesial root were selected after root anatomy pairing by microcomputed tomography
      (microCT). The teeth were randomly divided into five groups (n = 24); the root
      canal volume was calculated to ensure sample homogeneity. All the root canals
      were prepared up to size 25 in accordance with the instructions of each rotary
      system manufacturer. After root canal preparation, the teeth were scanned by
      microCT to analyse apical transportation, root canal centralization and the pre-
      and post-preparation root canal volume at the apical and cervical levels. Kruskal
      Wallis and Dunn tests were used for comparisons amongst groups for transportation
      values. For volume changes, the parametric ANOVA and Tukey's tests were used
      RESULTS: There were no significant differences in apical transportation amongst
      the rotary systems (P > 0.05). All the systems created apical transportation;
      values ranging from 0.031 mm (PDL) to 0.072 mm (PTG), and enlargements between
      39% (HCM) and 91.1% (PDS) were observed. In relative to cervical transportation,
      significant differences were observed amongst the systems (P < 0.05). Mean
      transportation values between 0.07 mm (HCM) and 0.172 mm (PTG) were found, with
      enlargements between 35.4% (HCM) and 51.5% (PDS). CONCLUSION: All the thermally
      treated systems resulted in similar apical transportation. In the cervical
      region, the Hyflex CM and Prodesign Logic systems were associated with more
      centred preparations.

PMID- 29178174
TI  - Health education needs of intimate partner violence survivors: Perspectives from
      female survivors and social service providers.
AB  - OBJECTIVE: To explore the health education needs and learning preferences of
      female intimate partner violence (IPV) survivors in a social service agency
      located in South Florida, United States. DESIGN AND SAMPLE: An exploratory two
      phase sequential mixed-methods study was completed through semistructured
      interviews with social service providers (n = 10), followed by a survey with
      predominately female IPV survivors (n = 122, 98.4%). MEASURES: Data obtained from
      interviews with social service providers were analyzed through conventional
      thematic content analysis. Data from interviews were used in developing a health
      survey completed by IPV survivors and analyzed utilizing descriptive statistics,
      chi-square tests and t tests. RESULTS: Three themes emerged from interviews
      including multidimensional health needs, navigating barriers to health care, and
      self-improvement specific to survivors of intimate partner violence. Survey
      results indicated that depression and self-esteem were the health education needs
      of highest priority. Demographic characteristics, including age and language use,
      were significantly associated to preferred methods of learning, p < .05.
      CONCLUSIONS: IPV survivors present with various health education needs. Current
      study findings can inform public health nurses in developing interventions or
      health-based programs for female IPV survivors in social service agency settings.

PMID- 29178175
TI  - Effect of Dairy Cow Crossbreeding on Selected Performance Traits and Quality of
      Milk in First Generation Crossbreds.
AB  - : The main goal of crossbreeding Holstein-Friesian (HF) cows with bulls of other
      dairy or combined breeds is to improve their performance traits. Thus, the aim of
      this investigation was to compare the dairy performance traits of first
      generation crossbreds produced by crossbreeding Polish HF cows with bulls of
      other breeds (Norman, Norwegian Red, Danish Red, Brown Swiss, Montbeliarde, and
      Simmental). This was done by analyzing the fatty acid profile and technological
      quality of the milk from these first generation crossbreds. The investigation
      showed that crossbreeding greatly influenced the performance parameters and
      technological quality of the milk of the first generation crossbreds obtained
      from crossbreeding Polish HF cows with bulls of other dairy or combined breeds.
      The crossbreed cows characterized by the highest both quantity and quality of
      milk. Also, the best parameters of milk fat dispersion (that is, the highest
      values of these parameters) that are useful in the production of hard ripening
      cheeses and butter were found in the milk of crossbreed cows. Health
      beneficially, saturated fatty acids level in milk of crossbreeds was by 25.96%
      lower in crossbreds milk when compared to purebred cows. The most beneficial
      content of whey proteins was found in the milk of Polish HF and Norwegian Red
      crosses, where it was 19.04% higher than in pure breed Holsteins. F1 cows tend to
      express better functional traits than Holstein (PHF) cows. Effect of heterosis
      was larger and gave better results when there was a greater genetic distance
      between the animals used for crossbreeding. PRACTICAL APPLICATION: The effects of
      heterosis are opposite to the effects of inbreeding depression, and it extends
      the lifespan and use of animals as well as improves their fertility and health.
      The main goal of crossbreeding Holstein-Friesian cows with bulls of other dairy
      or combined breeds is to improve their performance traits. F1 cows tend to
      express better functional traits than Holstein (PHF) cows. Effect of heterosis
      was larger and gave better results when there was a greater genetic distance
      between the animals used for crossbreeding.

PMID- 29178176
TI  - Updated Estimates Suggest a Much Higher Prevalence of Arthritis in United States
      Adults Than Previous Ones.
AB  - OBJECTIVE: National estimates of arthritis prevalence rely on a single survey
      question about doctor-diagnosed arthritis without using survey information on
      joint symptoms, even though some subjects with only the latter have been shown to
      have arthritis. The sensitivity of the current surveillance definition is only
      53% and 69% in subjects ages 45-64 years and ages >=65 years, respectively,
      resulting in misclassification of nearly one-half and one-third of subjects in
      those age groups. This study was undertaken to estimate arthritis prevalence
      based on an expansive surveillance definition that is adjusted for the
      measurement errors in the current definition. METHODS: Using the 2015 National
      Health Interview Survey, we developed a Bayesian multinomial latent class model
      for arthritis surveillance based on doctor-diagnosed arthritis, joint symptoms,
      and whether symptom duration exceeded 3 months. RESULTS: Of 33,672 participants,
      19.3% of men and 16.7% of women ages 18-64 years and 15.7% of men and 13.5% of
      women ages >=65 years affirmed joint symptoms without doctor-diagnosed arthritis.
      The measurement error-adjusted prevalence of arthritis was 29.9% (95% Bayesian
      probability interval [95% PI] 23.4-42.3) in men ages 18-64 years, 31.2% (95% PI
      25.8-44.1) in women ages 18-64 years, 55.8% (95% PI 49.9-70.4) in men ages >=65
      years, and 68.7% (95% PI 62.1-79.9) in women ages >=65 years. Arthritis affected
      91.2 million adults (of 247.7 million; 36.8%) in the US in 2015, which included
      61.1 million persons between 18 and 64 years of age (of 199.9 million; 30.6%).
      Our arthritis prevalence estimate was 68% higher than the previously reported
      national estimate. CONCLUSION: Arthritis prevalence in the US population has been
      substantially underestimated, especially among adults younger than 65 years of
      age.

PMID- 29178177
TI  - Cargo crowding at actin-rich regions along axons causes local traffic jams.
AB  - Steady axonal cargo flow is central to the functioning of healthy neurons.
      However, a substantial fraction of cargo in axons remains stationary up to
      several minutes. We examine the transport of precursors of synaptic vesicles (pre
      SVs), endosomes and mitochondria in Caenorhabditis elegans touch receptor
      neurons, showing that stationary cargo are predominantly present at actin-rich
      regions along the neuronal process. Stationary vesicles at actin-rich regions
      increase the propensity of moving vesicles to stall at the same location,
      resulting in traffic jams arising from physical crowding. Such local traffic jams
      at actin-rich regions are likely to be a general feature of axonal transport
      since they also occur in Drosophila neurons. Repeated touch stimulation of C.
      elegans reduces the density of stationary pre-SVs, indicating that these traffic
      jams can act as both sources and sinks of vesicles. This suggests that vesicles
      trapped in actin-rich regions are functional reservoirs that may contribute to
      maintaining robust cargo flow in the neuron. A video abstract of this article can
      be found at: Video S1; Video S2.

PMID- 29178179
TI  - Multimodal imaging of posterior ocular involvement in McArdle's disease.

PMID- 29178178
TI  - Left ventricular dispersion as a parameter for augmented left ventricular stroke
      volume in patients with atrial septal defect following transcatheter closure.
AB  - OBJECTIVES: The closure of atrial septal defect (ASD) results in normalized left
      ventricular (LV) and right ventricular (RV) geometry, and can increase LV stroke
      volume (LVSV), but the parameters associated with this increase after the closure
      of ASD remain uncertain. METHODS: Seventy ASD patients, who underwent
      transcatheter closure, were studied. Their mean age was 57.80 +/- 16.88 years, 42
      (60%) were female, and LV ejection fraction (LVEF) was 66.76% +/- 7.91% (all
      >=55%). Transthoracic echocardiography was performed before and 3 months after
      the procedure. Global longitudinal strain (GLS) was determined as the average
      peak speckle tracking strain of 18 segments from the 3 standard apical views, LV
      dispersion was defined as standard deviation of time-to-peak strain from the same
      views, and RV systolic function was calculated by averaging the 3-regional peak
      speckle tracking longitudinal strains from the RV free wall. A significant
      relative increase in LVSV between before and 3 months after the closure was
      defined as ?LVSV >=15%. Twenty age-, gender-, and LVEF-matched controls served as
      the control group. RESULTS: Global longitudinal strain (GLS) and RV free wall
      strain were similar for ASD patients and controls, but LV dispersion in ASD
      patients was significantly larger. Global longitudinal strain (GLS) remained
      unchanged after transcatheter closure, whereas RV free wall strain and LV
      dispersion decreased significantly. An important finding of the multivariate
      logistic regression analysis showed that ?LV dispersion was the only independent
      determinant of increased LVSV after the closure (OR 1.023; 95% CI 1.001-1.046; P
      < .01). CONCLUSIONS: The assessment of LV dispersion may well have clinical
      implications for better management of ASD patients after transcatheter closure.

PMID- 29178180
TI  - High-density lipoprotein from end-stage renal disease patients exhibits superior
      cardioprotection and increase in sphingosine-1-phosphate.
AB  - BACKGROUND: Chronic kidney disease (CKD) exacerbates the risk of death due to
      cardiovascular disease (CVD). Modifications to blood lipid metabolism which
      manifest as increases in circulating triglycerides and reductions in high-density
      lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD
      patients, higher HDL cholesterol levels were not associated with reduced
      mortality risk. Recent research has revealed numerous mechanisms by which HDL
      could favourably influence CVD risk. In this study, we compared plasma levels of
      sphingosine-1-phosphate (S1P), HDL-associated S1P (HDL-S1P) and HDL-mediated
      protection against oxidative stress between CKD and control patients. METHODS:
      High-density lipoprotein was individually isolated from 20 CKD patients and 20
      controls. Plasma S1P, apolipoprotein M (apoM) concentrations, HDL-S1P content and
      the capacity of HDL to protect cardiomyocytes against doxorubicin-induced
      oxidative stress in vitro were measured. RESULTS: Chronic kidney disease patients
      showed a typical profile with significant reductions in plasma HDL cholesterol
      and albumin and an increase in triglycerides and pro-inflammatory cytokines (TNF
      alpha and IL-6). Unexpectedly, HDL-S1P content (P = .001) and HDL
      cardioprotective capacity (P = .034) were increased significantly in CKD
      patients. Linear regression analysis of which factors could influence HDL-S1P
      content showed an independent, negative and positive association with plasma
      albumin and apoM levels, respectively. DISCUSSION: The novel and unexpected
      observation in this study is that uremic HDL is more effective than control HDL
      for protecting cardiomyocytes against oxidative stress. It is explained by its
      higher S1P content which we previously demonstrated to be the determinant of HDL
      mediated cardioprotective capacity. Interestingly, lower concentrations of
      albumin in CKD are associated with higher HDL-S1P.

PMID- 29178181
TI  - Hereditary hypochromic microcytic anemia associated with loss-of-function DMT1
      gene mutations and absence of liver iron overload.

PMID- 29178182
TI  - Social networks, health promoting-behavior, and health-related quality of life in
      older Korean adults.
AB  - In this cross-sectional, descriptive study, we compared the sociodemographic
      characteristics, social networks, health-promoting behavior, and the health
      related quality of life of older Korean adults living in South Korea to those of
      older Korean adult immigrants living in the USA. A total of 354 older adults,
      aged 65 years or older, participated. Data were collected through self-directed
      questionnaires, and analyzed using a two way analysis of variance, t-tests, chi2 
      tests, and Pearson's correlation coefficient. The association between four
      sociodemographic characteristics and health-related quality of life was
      significantly different between the two groups. For the older Korean adults
      living in South Korea, positive correlations existed between a measure of their
      social networks and both health-promoting behavior and health-related quality of
      life. For the older Korean immigrants, the findings revealed a positive
      correlation only between social networks and health-promoting behavior. The study
      findings support the important association social networks can have with health
      related quality of life, and their possible relationship to health-promoting
      behaviors of older Korean adults. We suggest that health policy-makers and
      healthcare providers develop comprehensive programs that are designed to improve
      older adults' social networks.

PMID- 29178183
TI  - Predictors of an abnormal postexercise ankle brachial index: Importance of the
      lowest ankle pressure in calculating the resting ankle brachial index.
AB  - BACKGROUND: The postexercise ankle-brachial index (ABI) is useful in patients
      with suspected peripheral arterial disease (PAD) and a normal resting ABI. Our
      objective was to determine the independent predictors of an abnormal postexercise
      ABI. HYPOTHESIS: We hypothesized that the lowest ankle systolic pressure to
      calculate the resting ABI would be associated with an abnormal post-exercise ABI.
      METHODS: Among 619 consecutive patients referred for suspected PAD, we calculated
      the postexercise ABI in patients with a normal resting ABI. An ABI <0.90 at rest
      was considered abnormal. We investigated 3 definitions of an abnormal
      postexercise ABI, defined as either <0.90, or >5% or >20% reduction compared with
      rest. RESULTS: Using multivariate analysis, the lowest ABI (calculated using the
      lowest and not the highest ankle systolic pressure) was consistently the most
      powerful independent predictor of an abnormal postexercise ABI. Patients with an
      abnormal lowest resting ABI were significantly more likely to have an abnormal
      postexercise ABI, as well as a significantly greater reduction in the ABI
      compared with rest. The lowest ABI had a high specificity (95%) but low
      sensitivity (82%) for a postexercise ABI <0.90. CONCLUSIONS: An abnormal lowest
      ABI (calculated with the lowest ankle systolic pressure) is the most important
      independent predictor of an abnormal ABI response to exercise in patients with a
      conventionally normal ABI. All such patients should be exercised and their ABI
      measured postexercise.

PMID- 29178184
TI  - Anatomy of the pedicled anterolateral thigh flap for phalloplasty in
      transitioning-males.
AB  - Incidence of transexualism and request for neophalloplasty is increasing yielding
      a current prevalence of trans-male in the USA of 1:2500. Surgeons have explored
      various techniques to improve desirable outcomes of neophallic construction,
      decrease the length of surgery, and minimize stigmatizing scars. The
      anterolateral thigh (ALT) flap is an alternative to the traditional radial
      forearm flap for patients who do not want a forearm scar. Surgical text
      descriptions were enhanced by the creation of new anatomic illustrations. Anatomy
      of the donor and recipient sites as well as the surgical technique leading to
      creation of the neophallus are demonstrated in detail with new relevant
      illustrations. The ALT flap is a skin, fat and fascia flap that is usually
      supplied by the descending branch of the lateral circumflex femoral vessels and
      the lateral femoral cutaneous nerve. However, variability in neurovascular supply
      does exist with important clinical implications. In the pedicled surgical
      procedure, neurovascular supply is left partly attached to the donor site
      ("pedicle") and simply transposed to the perineum, keeping the pedicle intact as
      a conduit to supply the tissue with blood and innervation. ALT flap offers
      clinical advantages of less obvious donor site concealable with clothing,
      decreased surgical time, preservation of erogenous sensation and vascular supply
      of the flap without microsurgical anastomosis of nerves and vessels, and good
      potential for urethroplasty. This surgery may be difficult in patients with
      thicker skin and more subcutaneous thigh fat. Clin. Anat, 2017. (c) 2017 Wiley
      Periodicals, Inc. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178185
TI  - Case series of outcomes of a standardized surgical approach for placenta percreta
      for prevention of ureteral lesions.
AB  - OBJECTIVE: To report the outcomes of women with placenta percreta who were
      surgically treated by a specialized technique based on gynecologic oncology
      experience, and to demonstrate its safety in preventing ureteral lesions and
      reducing blood loss. METHODS: In the present retrospective study, data from
      patients with placenta percreta radically treated at Hotel-Dieu de France,
      Beirut, Lebanon, between December 2012 and January 2017 were reviewed.
      Demographic, pathology, and delivery data, medical history, per-operative and
      postoperative information, and neonatal data were assessed. Operative and
      postoperative outcomes were compared between emergency and scheduled cases.
      RESULTS: Data from 35 patients were reviewed. Median gestational age at delivery
      was 34 weeks. Cesarean hysterectomy was scheduled in 20 (60%) cases. No ureteral
      lesions were noted. The median estimated blood loss was 1 L and a median of 3
      units of red blood cells units was transfused. Emergency and scheduled cases
      presented comparable estimated blood loss, intra-operative transfusion, bladder
      injury incidence, and surgery duration (all P>0.05). The mean delivery weight was
      2100 g; admission to the neonatal intensive care unit was needed for 30 (86%)
      neonates. CONCLUSION: The surgical technique developed for placenta percreta was
      found to be effective (operative and postoperative outcomes) and safe (prevention
      of ureteral lesions).

PMID- 29178188
TI  - Characterization of the enzymatic activity and physiological function of the
      lipid droplet-associated triacylglycerol lipase AtOBL1.
AB  - Similar to seeds, pollen tubes contain lipid droplets that store triacylglycerol
      (TAG), but the fate of this TAG as well as the enzymes involved in its breakdown
      are unknown. Therefore, two potential TAG lipases from tobacco and Arabidopsis,
      NtOBL1 (Oil body lipase 1) and AtOBL1, were investigated, especially with respect
      to their importance for pollen tube growth. We expressed NtOBL1 and AtOBL1 as
      fluorescent fusion proteins to study their localization by confocal microscopy.
      Furthermore, we overexpressed AtOBL1 in Nicotiana benthamiana leaves to
      characterize it enzymatically. The obl1 mutant was studied in respect to its
      pollen tube growth in vivo and its seed germination. Both NtOBL1 and AtOBL1
      localized to lipid droplets. AtOBL1 was abundant in pollen tubes and seedlings,
      and acted as a lipase on TAG, diacylglycerol and 1-monoacylglycerol at a pH
      optimum of 5.5. The obl1 mutant was hampered in pollen tube growth, whereas
      seedling establishment was not affected under optimal conditions, even though
      AtOBL1 accounted for a major lipase activity in seeds. TAG could be a direct
      precursor for the synthesis of membrane lipids in pollen tubes and proteins of
      the OBL family involved in the flux of acyl groups.

PMID- 29178186
TI  - Mammary epithelium-specific inactivation of V-ATPase reduces stiffness of
      extracellular matrix and enhances metastasis of breast cancer.
AB  - Extracellular matrix (ECM) critically impacts tumor progression and is influenced
      by both cancer and host tissue cells. While our understanding of cancer cell ECM
      remodeling is widespread, the importance of host tissue ECM, which provides
      initial congenial environment for primary tumor formation, is partly understood.
      Here, we report a novel role of epithelial cell-associated vacuolar ATPase 'a2'
      isoform (a2V) in regulating breast tissue ECM stiffness to control metastasis.
      Using a mammary gland-specific a2V-knockout model, we show that in the absence of
      a2V, breast tumors exhibit atypically soft tumor phenotype, less tumor rigidity,
      and necrotic tumor microenvironment. These tumors contain a decreased number of
      cancer cells at primary tumor site, but showed extensive metastases compared to
      control. Nanomechanical evaluation of normal breast tissues revealed a decrease
      in stiffness and collagen content in ECM of a2V-deleted breast tissues.
      Mechanistically, inhibition of a2V expression caused dispersed Golgi morphology
      with relocation of glycosyltransferase enzymes to early endosomes in mammary
      epithelial cells. This resulted in defective glycosylation of ECM proteins and
      production of compromised ECM that further influenced tumor metastasis.
      Clinically, in patients with cancer, low a2V expression levels in normal breast
      tissue correlated with lymph node metastasis. Thus, using a new knockout mouse
      model, we have identified a2V expression in epithelial cells as a key requirement
      for proper ECM formation in breast tissue and its expression levels can
      significantly modulate breast tumor dissemination. Evaluation of a2V expression
      in normal breast tissues can help in identifying patients with high risk of
      developing metastases.

PMID- 29178189
TI  - Toothbrushing behaviour and periodontal pocketing: An 11-year longitudinal study.
AB  - AIM: To explore the association between toothbrushing behaviour and change in
      periodontal pocketing among adults. METHODS: We pooled data from 1,025 adults,
      aged 30-89 years, who participated in two national surveys in Finland (Health
      2000 and Health 2011, BRIF8901) and reported their toothbrushing frequency. A
      cumulative measure of regular toothbrushing was created by counting the number of
      times participants reported brushing twice or more daily across the two surveys
      (ranging from 0 to 2). The association between toothbrushing behaviour and the
      number of teeth with periodontal pocket depth (PPD) >=4 mm over 11 years was
      assessed in linear regression models adjusting for confounders. RESULTS: There
      was a clear dose-response relationship between toothbrushing frequency (either at
      baseline or follow-up) and change in number of teeth with PPD >= 4 mm. There was
      also evidence of a cumulative effect of regular toothbrushing on change in number
      of teeth with PPD >= 4 mm. Participants who reported brushing twice or more a day
      in both surveys developed 1.99 (95% CI: 1.02-2.95) fewer teeth with PPD >= 4 mm
      than those who did not report this behaviour in any survey. CONCLUSION: This 11
      year prospective study showed that toothbrushing behaviour was associated with
      smaller increments in the number of teeth with periodontal pocketing.

PMID- 29178191
TI  - Cutaneous granuloma caused by Rhizopus oryzae with a novel mutation in the CYBB
      gene in a monozygotic male twin.

PMID- 29178190
TI  - A Perspective on Bio-Mediated Material Structuring.
AB  - Bioinspiration, biomorphy, biomimicry, biomimetics, bionics, and biotemplating
      are terms used to describe the fabrication of materials or, more generally,
      systems to solve technological problems by abstracting, emulating, using, or
      transferring structures from biological paradigms. Herein, a brief overview of
      how the different terminologies are being typically applied is provided. It is
      proposed that there is a rich field of research that can be expanded by utilizing
      various novel approaches for the guidance of living organisms for "bio-mediated"
      material structuring purposes. As examples of contact-based or contact-free
      guidance, such as substrate patterning, the application of light, magnetic
      fields, or chemical gradients, potentially interesting methods of creating
      hierarchically structured monolithic engineering materials, using live patterned
      biomass, biofilms, or extracellular substances as scaffolds, are presented. The
      potential advantages of such materials are discussed, and examples of live self
      patterning of materials are given.

PMID- 29178192
TI  - Mutagenic primer-based PCR-RFLP assay for genotyping IRGM gene promoter variant
      rs4958843 (C/T).
AB  - BACKGROUND: Single-nucleotide polymorphisms play an important role in the
      susceptibility of many diseases, evolutionary studies, and genetic mapping. The
      rs4958843 in IRGM promoter is associated with tuberculosis and Crohn's disease.
      As this SNP is not present in any of the restriction sites, PCR-RFLP is not
      possible. Therefore, we have developed artificial-RFLP method to genotype this
      SNP. METHODS: We designed forward primer with mismatches that resulted in the
      creation of a restriction site for enzyme NheI in the amplicon. Control samples
      of known genotypes were obtained by sequencing. The amplified product for SNP
      rs4958843 was digested with NheI restriction enzyme and resolved on an agarose
      gel to know the genotypes of the samples. RESULTS: Results of sequencing and A
      RFLP were concordant. The developed method was applied to genotype this
      polymorphism in 100 samples from healthy individuals. The allelic frequencies of
      SNP rs4958843 were C (0.16) and T (0.84), while corresponding genotypic
      distribution was CC (2), CT (29), and TT (69). CONCLUSION: The newly developed
      method is simple, easy, and cost-effective which could be used to genotype IRGM
      polymorphism -1161 C/T (rs4958843) in various populations in the replication
      studies and has its applicability in the clinical settings. The developed method
      was applied for genotyping samples from healthy individuals from North India. For
      the first time, we report the frequency of this polymorphism from this region.

PMID- 29178193
TI  - Proteomic Characterization of Caenorhabditis elegans Larval Development.
AB  - The nematode Caenorhabditis elegans is widely used as a model organism to study
      cell and developmental biology. Quantitative proteomics of C. elegans is still in
      its infancy and, so far, most studies have been performed on adult worm samples.
      Here, we used quantitative mass spectrometry to characterize protein level
      changes across the four larval developmental stages (L1-L4) of C. elegans. In
      total, we identified 4130 proteins, and quantified 1541 proteins that were
      present across all four stages in three biological replicates from independent
      experiments. Using hierarchical clustering and functional ontological analyses,
      we identified 21 clusters containing proteins with similar protein profiles
      across the four stages, and highlighted the most overrepresented biological
      functions in each of these protein clusters. In addition, we used the dataset to
      identify putative larval stage-specific proteins in each individual developmental
      stage, as well as in the early and late developmental stages. In summary, this
      dataset provides system-wide analysis of protein level changes across the four C.
      elegans larval developmental stages, which serves as a useful resource for the C.
      elegans research community. MS data were deposited in ProteomeXchange
      (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository
      with the primary accession identifier PXD006676.

PMID- 29178194
TI  - Aplasia cutis congenita: Evaluation of signs suggesting extracutaneous
      involvement.
AB  - Specific clinical features of aplasia cutis congenita may indicate the presence
      of underlying cranial or cerebrovascular defects, allowing for early recognition
      and intervention. Most information about aplasia cutis congenita exists as
      individual case reports, with few large-scale studies. We conducted a 7-year
      retrospective chart review of 90 cases of aplasia cutis congenita and identified
      clinical characteristics including morphology, number of lesions, anatomic
      location, presence of hair collar sign, associated cutaneous features, histology,
      and imaging results. The anatomic location of the lesion (vertex, midline) (P =
      .01), presence of hair collar sign (P < .001), vascular stains (P < .001), and
      nodules (P = .007) were found to be strong clinical indicators of skull or
      cerebrovascular involvement.

PMID- 29178195
TI  - Introducing Glycerol as a Sustainable Solvent to Organolithium Chemistry:
      Ultrafast Chemoselective Addition of Aryllithium Reagents to Nitriles under Air
      and at Ambient Temperature.
AB  - Edging closer towards developing air and moisture compatible polar organometallic
      chemistry, the chemoselective and ultrafast addition of a range of aryllithium
      reagents to nitriles has been accomplished by using glycerol as a solvent, at
      ambient temperature in the presence of air, establishing a novel sustainable
      access to aromatic ketones. Addition reactions occur heterogeneously ("on
      glycerol conditions"), where the lack of solubility of the nitriles in glycerol
      and the ability of the latter to form strong intermolecular hydrogen bonds seem
      key to favouring nucleophilic addition over competitive hydrolysis. Remarkably,
      PhLi exhibits a greater resistance to hydrolysis working "on glycerol" conditions
      than "on water". Introducing glycerol as a new solvent in organolithium chemistry
      unlocks a myriad of opportunities for developing more sustainable, air and
      moisture tolerant main-group-metal-mediated organic synthesis.

PMID- 29178196
TI  - Comparative transcriptomic analysis of larval and adult Malpighian tubules from
      the cotton bollworm Helicoverpa armigera.
AB  - Malpighian tubules (MTs) are usually considered the key excretory and
      osmoregulatory organs of insects. However, increasing evidence has suggested that
      MTs perform many more functions than just osmoregulation. Until now, the
      molecular and physiological functions of MTs in the cotton bollworm (Helicoverpa
      armigera), a very important agricultural pest, are largely unknown. In this
      study, the transcriptomes of H. armigera MTs from larvae, male adults and female
      adults were sequenced using RNA-Seq technology, and comparative analyses of
      transcriptomes between two life stages (larval and adult) and between adult sexes
      were conducted. We generated a total of 84 643 high-quality unigenes, and
      identified a large number of abundant transcripts putatively encoding proteins
      involved in diuresis, detoxification, immunity, carbohydrate transport and
      metabolism, development and reproduction. We found that the expression pattern of
      unigenes was relatively similar between female and male adult MTs, but different
      between larval and adult MTs. Our data suggest that insect MTs may take multiple
      physiological functions as versatile organs. The extensive alterations in gene
      expression in MTs occurred from larvae to adults reflect an ecological adaptation
      to different feeding habits. Sexual dimorphism in the cotton bollworm is somewhat
      indicated by the transcriptional difference of genes related to carbohydrate
      metabolism, detoxification, immunity and reproduction in the MTs of male and
      female adults.

PMID- 29178197
TI  - Greater retention in care among adolescents on antiretroviral treatment accessing
      "Teen Club" an adolescent-centred differentiated care model compared with
      standard of care: a nested case-control study at a tertiary referral hospital in
      Malawi.
AB  - INTRODUCTION: There are numerous barriers to the care and support of adolescents
      living with HIV (ALHIV) that makes this population particularly vulnerable to
      attrition from care, poor adherence and virological failure. In 2010, a Teen Club
      was established in Zomba Central Hospital (ZCH), Malawi, a tertiary referral HIV
      clinic. Teen Club provides ALHIV on antiretroviral treatment (ART) with dedicated
      clinic time, sexual and reproductive health education, peer mentorship, ART
      refill and support for positive living and treatment adherence. The purpose of
      this study was to evaluate whether attending Teen Club improves retention in ART
      care. METHODS: We conducted a nested case-control study with stratified
      selection, using programmatic data from 2004 to 2015. Cases (ALHIV not retained
      in care) and controls (ALHIV retained in care) were matched by ART initiation age
      group. Patient records were reviewed retrospectively and subjects were followed
      starting in March 2010, the month in which Teen Club was opened. Follow-up ended
      at the time patients were no longer considered retained in care or on 31 December
      2015. Cases and controls were drawn from a study population of 617 ALHIV. Of
      those, 302 (48.9%) participated in at least two Teen Club sessions. From the
      study population, 135 (non-retained) cases and 405 (retained) controls were
      selected. RESULTS: In multivariable analyses, Teen Club exposure, age at the time
      of selection and year of ART initiation were independently associated with
      attrition. ALHIV with no Teen Club exposure were less likely to be retained than
      those with Teen Club exposure (adjusted odds ratio (aOR) 0.27; 95% CI 0.16, 0.45)
      when adjusted for sex, ART initiation age, current age, reason for ART initiation
      and year of ART initiation. ALHIV in the age group 15 to 19 were more likely to
      have attrition from care than ALHIV in the age group 10 to 14 years of age (aOR
      2.14; 95% CI 1.12, 4.11). CONCLUSIONS: This study contributes to the limited
      evidence evaluating the effectiveness of service delivery interventions to
      support ALHIV within healthcare settings. Prospective evaluation of the Teen Club
      package with higher methodological quality is required for programmes and
      governments in low- and middle-income settings to prioritize interventions for
      ALHIV and determine their cost-effectiveness.

PMID- 29178198
TI  - Association between Helicobacter pylori infection and gallbladder diseases: A
      retrospective study.
AB  - BACKGROUND AND AIM: The association between Helicobacter pylori (H. pylori) and
      gallbladder diseases is still unclear and is controversial. We conducted a
      retrospective study to clarify the prevalence of gallbladder diseases and factors
      related to gallbladder diseases and relationships between H. pylori infection,
      gallstones, cholecystitis, and cholecystic polypus. METHODS: The retrospective
      study was performed at the Aerospace Center Hospital in Beijing. The subjects in
      this study were a healthy population who underwent health examinations at the
      hospital between 2012 and 2015. The logistic regression models were used to
      explore the relationships between H. pylori infection and gallbladder diseases.
      RESULTS: There were 7803 (43.4%) subjects with H. pylori infection, 995 (5.5%)
      with gallstones, 219 (1.2%) with cholecystitis, and 1003 (5.6%) with cholecystic
      polypus amongst 17 971 subjects, respectively. In subjects aged 45 years or less,
      the prevalence of gallstones in the H. pylori (+) group was lower than that in
      the H. pylori (-) group (odds ratio = 0.653; 95% confidence interval: 0.468
      0.911; P = 0.012). The prevalence of cholecystic polypus in the H. pylori (+)
      group was significantly higher than that in the H. pylori (-) group (odds ratio =
      1.160; 95% confidence interval: 1.012-1.328; P = 0.033). CONCLUSIONS:
      Helicobacter pylori infection was related with cholecystic polypus and gallstones
      in a Chinese population.

PMID- 29178199
TI  - Hematopoietic Niche - Exploring Biomimetic Cues to Improve the Functionality of
      Hematopoietic Stem/Progenitor Cells.
AB  - The adult bone marrow (BM) niche is a complex entity where a homeostatic
      hematopoietic system is maintained through a dynamic crosstalk between different
      cellular and non-cellular players. Signaling mechanisms triggered by cell-cell,
      cell-extracellular matrix (ECM), cell-cytokine interactions, and local
      microenvironment parameters are involved in controlling quiescence, self-renewal,
      differentiation, and migration of hematopoietic stem/progenitor cells (HSPC). A
      promising strategy to more efficiently expand HSPC numbers and tune their
      properties ex vivo is to mimic the hematopoietic niche through integration of
      adjuvant stromal cells, soluble cues, and/or biomaterial-based approaches in HSPC
      culture systems. Particularly, mesenchymal stem/stromal cells (MSC), through
      their paracrine activity or direct contact with HSPC, are thought to be a
      relevant niche player, positioning HSPC-MSC co-culture as a valuable platform to
      support the ex vivo expansion of hematopoietic progenitors. To improve the
      clinical outcome of hematopoietic cell transplantation (HCT), namely when the
      available HSPC are present in a limited number such is the case of HSPC collected
      from umbilical cord blood (UCB), ex vivo expansion of HSPC is required without
      eliminating the long-term repopulating capacity of more primitive HSC. Here, we
      will focus on depicting the characteristics of co-culture systems, as well as
      other bioengineering approaches to improve the functionality of HSPC ex vivo.

PMID- 29178200
TI  - The interrupted learner: How distractions during live and video lectures
      influence learning outcomes.
AB  - New instructional technologies have been increasingly incorporated into the
      medical school learning environment, including lecture video recordings as a
      substitute for live lecture attendance. The literature presents varying
      conclusions regarding how this alternative experience impacts students' academic
      success. Previously, a multi-year study of the first-year medical histology
      component at the University of Michigan found that live lecture attendance was
      positively correlated with learning success, while lecture video use was
      negatively correlated. Here, three cohorts of first-year medical students (N =
      439 respondents, 86.6% response rate) were surveyed in greater detail regarding
      lecture attendance and video usage, focusing on study behaviors that may
      influence histology learning outcomes. Students who reported always attending
      lectures or viewing lecture videos had higher average histology scores than
      students who employed an inconsistent strategy (i.e., mixing live attendance and
      video lectures). Several behaviors were negatively associated with histology
      performance. Students who engaged in "non-lecture activities" (e.g., social media
      use), students who reported being interrupted while watching the lecture video,
      or feeling sleepy/losing focus had lower scores than their counterparts not
      engaging in these behaviors. This study suggests that interruptions and
      distractions during medical learning activities-whether live or recorded-can have
      an important impact on learning outcomes. Anat Sci Educ 11: 366-376. (c) 2017
      American Association of Anatomists.

PMID- 29178202
TI  - Shape disparity of bovid (Mammalia, Artiodactyla) horn sheaths and horn cores
      allows discrimination by species in 3D geometric morphometric analyses.
AB  - The bony cranial structures of even-toed hoofed mammals are important for
      understanding ecology and behavior of ruminants. Horns, the cranial appendages of
      the family Bovidae, are covered in a layer of keratin that is often not preserved
      in the fossil record; however, this keratin sheath is intimately involved in the
      processes that influence horn shape evolution. To understand the relationship
      between these two components of horns, we quantified both core and sheath shape
      for four extant species using three-dimensional geometric morphometric analyses
      in separate, core- and sheath-specific morphospaces as well as a combined
      morphospace. We assessed correlations between the horn and sheath morphospaces
      using two-block partial least squares regression, a Mantel test of pairwise
      distances between species, and Procrustes ANOVA. We measured disparity in the
      combined morphospace as Procrustes distances between mean shapes of cores and
      sheaths within and between species and as Procrustes variance. We also tested
      whether core and sheath shapes could be discriminated by taxon with a canonical
      variate analysis. Results show that horn core and sheath morphospaces are
      strongly correlated. The differences in shape between a species' core and sheath
      were statistically significant, but not as great as those between the cores and
      sheaths of different species when close relatives were not considered, and core
      and sheath Procrustes variances are not significantly different within species.
      Cores and sheath shapes were highly identifiable and were assigned to the correct
      clade 93% of the time in the canonical variate analysis. Based on these tests,
      horn cores are distinguishable in geometric morphometric analyses, extending the
      possibility of using geometric morphometrics to study the ecology and evolution
      of bovid horns to the fossil record.

PMID- 29178201
TI  - A Water-/Fireproof Flexible Lithium-Oxygen Battery Achieved by Synergy of Novel
      Architecture and Multifunctional Separator.
AB  - To meet the increasing demands for portable and flexible devices in a rapidly
      developing society, it is urgently required to develop highly safe and flexible
      electrochemical energy-storage systems. Flexible lithium-oxygen batteries with
      high theoretical specific energy density are promising candidates; however, the
      conventional half-open structure design prevents it from working properly under
      water or fire conditions. Herein, as a proof-of-concept experiment, a highly safe
      flexible lithium-oxygen battery achieved by the synergy of a vital
      multifunctional structure design and a unique composite separator is proposed and
      fabricated. The structure can effectively prevent the invasion of water from the
      environment and combustion, which is further significantly consolidated with the
      help of a polyimide and poly(vinylidene fluoride-co-hexafluoropropylene)
      composite separator, which holds good water resistance, thermal stability, and
      ionic conductivity. Unexpectedly, the obtained lithium-oxygen battery exhibits
      superior flexibility, water resistance, thermal resistance, and cycling stability
      (up to 218 cycles; at a high current of 1 mA and capacity of 4 mA h). This novel
      water/fireproof, flexible lithium-oxygen battery is a promising candidate to
      power underwater flexible electronics.

PMID- 29178203
TI  - The anatomy of the musculocutaneous latissimus dorsi flap for neophalloplasty.
AB  - In transgender surgery, the ideal neophallus is one that: (a) is constructed
      using a reproducible procedure, (b) possesses tactile and erogenous sensation,
      (c) is large and rigid enough (naturally, or using a prosthesis) to permit
      penetrative intercourse, (d) leaves acceptable donor site morbidity, (e) results
      in esthetically satisfactory appearance, and (f) allows for voiding while
      standing. The musculocutaneous latissimus dorsi (MLD) flap has favorable results
      in the area of neophalloplasty. Among its advantages are acceptable donor site
      appearance, stiffness sufficient for intercourse, and esthetically satisfactory
      genital appearance. The anatomy of the MLD flap supports the creation of a
      neophallus for transsexual anatomy revision. Herein, we give an overview of the
      advantages and disadvantages of the procedure, and the anatomical details and
      surgical steps involved. Novel illustrations were created from standard surgical
      text descriptions to clarify this topic for surgical training and patient
      understanding and decision making. A review of the relevant literature regarding
      the anatomy, procedure development, and outcomes is presented. The MLD flap uses
      part of the latissimus dorsi muscle with branches of the thoracodorsal vessels
      and nerve to construct a neophallus. A thin strip of muscle around the pedicle is
      harvested, resulting in a slightly curvilinear scar. The blood supply is
      connected to the femoral artery and saphenous vein or the deep inferior
      epigastric artery and vein, while the nerve is connected to the ilioinguinal
      nerve or the obturator nerve. The MLD flap for neophalloplasty is a reliable
      graft with a well concealed scar and low donor site morbidity. Clin. Anat. 31:152
      159, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178205
TI  - Outcomes of an enhancement study with additional psychoeducational sessions for
      healthy siblings of a child with cancer during inpatient family-oriented
      rehabilitation.
AB  - OBJECTIVE: Chronic illness of a child puts healthy children of the family at risk
      of distress. Previous studies have demonstrated that healthy children's
      psychological symptoms can be reduced when the child knows more about the
      disease. So far, there is limited evidence of the effectiveness of
      psychoeducational interventions for healthy children. AIMS: To compare the
      effectiveness of an inpatient family-oriented rehabilitation program with vs
      without additional psychoeducational sessions for healthy children of families
      with children with cancer. PATIENTS AND METHODS: We performed a controlled study
      in 4 German family-oriented rehabilitation clinics. The outcomes of n = 73
      healthy children (mean age: M = 9.55; SD = 3.14; range: 4-18), who participated
      in 5 additional psychoeducational sessions, were compared with the outcomes of n
      = 111 healthy children (mean age: M = 8.85; SD = 3.28; range: 4-17), who
      underwent the usual inpatient rehabilitation program. Primary outcomes were the
      healthy children's cancer-specific knowledge and their emotional symptoms.
      Secondary outcomes were family satisfaction and quality of life. RESULTS:
      Intention-to-treat analyses showed that both groups improved significantly from
      preintervention to postintervention. Improvements comprised knowledge about
      cancer (F(1,174) = 11.03, p < 0.001), self-reported emotional symptoms (F(1,135)
      = 31.68, p < 0.001), and parent-proxy-reported emotional symptoms (F(1,179) =
      37.07, p < 0.001). The additional psycho-educational program did not
      significantly enhance the outcomes. The same pattern of significant improvement
      in both conditions emerged for all secondary outcomes. The immediate effects of
      the intervention persisted until 2 months after discharge from the rehabilitation
      program. CONCLUSIONS: Inpatient family-oriented rehabilitation is effective in
      improving multiple psychosocial outcomes of healthy children in families which
      have a child with cancer. Additional psycho-educational sessions did not show any
      substantial additional improvement.

PMID- 29178204
TI  - TbSmee1 regulates hook complex morphology and the rate of flagellar pocket uptake
      in Trypanosoma brucei.
AB  - Trypanosoma brucei uses multiple mechanisms to evade detection by its insect and
      mammalian hosts. The flagellar pocket (FP) is the exclusive site of uptake from
      the environment in trypanosomes and shields receptors from exposure to the host.
      The FP neck is tightly associated with the flagellum via a series of cytoskeletal
      structures that include the hook complex (HC) and the centrin arm. These
      structures are implicated in facilitating macromolecule entry into the FP and
      nucleating the flagellum attachment zone (FAZ), which adheres the flagellum to
      the cell surface. TbSmee1 (Tb927.10.8820) is a component of the HC and a putative
      substrate of polo-like kinase (TbPLK), which is essential for centrin arm and FAZ
      duplication. We show that depletion of TbSmee1 in the insect-resident (procyclic)
      form of the parasite causes a 40% growth decrease and the appearance of
      multinucleated cells that result from defective cytokinesis. Cells lacking
      TbSmee1 contain HCs with aberrant morphology and show delayed uptake of both
      fluid-phase and membrane markers. TbPLK localization to the tip of the new FAZ is
      also blocked. These results argue that TbSmee1 is necessary for maintaining HC
      morphology, which is important for the parasite's ability to take up molecules
      from its environment.

PMID- 29178206
TI  - Co-occurrence and seasonal and environmental distributions of the sandflies
      Lutzomyia longipalpis and Nyssomyia whitmani in the city of Puerto Iguazu,
      northeastern Argentina.
AB  - The aim of this work was to study the distribution of Phlebotominae (Diptera:
      Psycodidade) abundance in time and space in an area in northeastern Argentina
      with vector transmission of visceral and tegumentary leishmaniasis. For this, 51
      households were selected using a 'worst scenario' criterion where one light trap
      was set during two consecutive nights in peridomiciles in the transitions between
      the four seasons, and the environment was surveyed simultaneously. The
      relationships of phlebotomine assemblage structure and the most abundant species
      with seasonality and environmental variables were evaluated using a canonical
      correspondence analysis and generalized linear mixed models, respectively. A
      total of 5110 individuals were captured. Lutzomyia longipalpis (Lutz & Neiva,
      1912) and Nyssomyia whitmani (Antunes & Coutinho, 1939) were the most abundant
      species captured in all samplings (98.3% of the total capture). The period of
      highest abundance of Lu. longipalpis was early autumn, and it was distributed in
      the most urbanized areas. Nyssomyia whitmani occupied mainly the less urbanized
      areas, showing peaks of abundance in early spring and summer. Other species were
      captured in low numbers and showed seasonal-spatial variations similar to those
      of Ny. whitmani. We confirmed Leishmania spp. vector persistence throughout the
      year in spatial patches of high abundance even during the less favorable season.

PMID- 29178207
TI  - Bullous pemphigoid inguinalis?

PMID- 29178208
TI  - Corrigendum: Enhanced Sensitivity and Piezochromic Contrast through Single
      Direction Extension of Molecular Structure.

PMID- 29178209
TI  - Harold Ross Roberts, MD, 1930-2017.

PMID- 29178210
TI  - Structure-activity investigation of the potentiating effect of cyano substitution
      on nitroaniline mutagenicity in the ames test.
AB  - 2,6-Dicyano-4-nitroaniline and 2-cyano-4-nitroaniline (CNNA; 2-amino-5
      nitrobenzonitrile) are potent mutagens in the Ames test, even though
      unsubstituted nitroanilines (NAs) are no more than weak mutagens. These compounds
      are putative reduction products of many commercial azo dyes, including Disperse
      Blue 165, Disperse Blue 337, Disperse Red 73, Disperse Red 82, Disperse Violet
      33, and Disperse Violet 63. We have examined the mutagenicity in strains TA98 and
      YG1024 of a series of commercially-available isomers of CNNA, and some related
      compounds, to probe the relationship between structure and genotoxic activity in
      this class of compounds. The potentiating effect of the cyano substituent is seen
      in many cases; e.g. 2-amino-4-nitrobenzonitrile is a much more potent mutagen
      than 3-NA. 2,4-Dinitrobenzonitrile is also highly mutagenic. Possible mechanisms
      for the "cyano effect" are considered, with respect to the likely structures of
      cyanonitroaniline-DNA adducts and the roles of the enzymes (nitroreductase and
      acetyl CoA:arylamine N-acetyltransferase) believed to be involved in the
      activation of nitroaromatic compounds. Environ. Mol. Mutagen. 59:114-122, 2018.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 29178211
TI  - Improving case study research in medical education: a systematised review.
AB  - CONTEXT: Case study research (CSR) is a research approach that guides holistic
      investigation of a real phenomenon. This approach may be useful in medical
      education to provide critical analyses of teaching and learning, and to reveal
      the underlying elements of leadership and innovation. There are variations in the
      definition, design and choice of methods, which may diminish the value of CSR as
      a form of inquiry. OBJECTIVES: This paper reports an analysis of CSR papers in
      the medical education literature. The review aims to describe how CSR has been
      used and how more consistency might be achieved to promote understanding and
      value. METHODS: A systematised review was undertaken to quantify the number of
      CSR articles published in scholarly medical education journals over the last 10
      years. A typology of CSR proposed by Thomas and Myers to integrate the various
      ways in which CSR is constructed was applied. RESULTS: Of the 362 full-text
      articles assessed, 290 were excluded as they did not meet the eligibility
      criteria; 76 of these were titled 'case study'. Of the 72 included articles, 50
      used single-case and 22 multi-case design; 46 connected with theory and 26 were
      atheoretical. In some articles it was unclear what the subject was or how the
      subject was being analysed. CONCLUSIONS: In this study, more articles titled
      'case study' failed than succeeded in meeting the eligibility criteria. Well
      structured, clearly written CSR in medical education has the potential to
      increase understanding of more complex situations, but this review shows there is
      considerable variation in how it is conducted, which potentially limits its
      utility and translation into education practice. Case study research might be of
      more value in medical education if researchers were to follow more consistently
      principles of design, and harness rich observation with connection of ideas and
      knowledge to engage the reader in what is most interesting.

PMID- 29178212
TI  - Evolution of diastolic function algorithms: Implications for clinical practice.
AB  - OBJECTIVE: We undertook this study of echocardiographic classification of
      diastolic function by three different algorithms to determine: (1) how frequently
      each algorithm classified patients and (2) how well the results agreed with one
      another. BACKGROUND: Several algorithms exist to grade diastolic function (DF),
      the Mayo Clinic scheme of Redfield et al (Mayo 2003) and the 2 ASE guideline
      documents of 2009 and 2016 (ASE 2009 and ASE 2016). METHODS: A total of 200
      consecutive echocardiograms were retrospectively analyzed; mean age of patients
      60.3 +/- 3.5 years, 45% male. Echocardiograms were performed using Intersocietal
      Accreditation Commission guidelines. Diastolic function was assessed by Mayo 2003
      and ASE 2009 and 2016. Coexisting conditions affecting DF analysis, such as
      mitral annular calcification (MAC), were tabulated. Data were compared using a
      paired t-test. Concordance between algorithms was assessed using the Kappa
      statistic. RESULTS: A total of 117 of 200 studies (58.5%) were excluded for the
      presence of coexisting conditions (51.5%), poor image quality (2.5%), or
      incomplete data (4.5%). Thirty-three of the remaining 83 studies (40%) received
      the same grade of DF based on assessments made using the Mayo 2003 and ASE 2016
      algorithms; the Kappa statistic was 0.20. 36 of the 83 studies (43%) received the
      same grade of DF based on assessments made using the ASE 2009 and ASE 2016
      algorithms; the Kappa statistic was 0.25. CONCLUSION: Assessment of diastolic
      function via echocardiography cannot be reliably accomplished in approximately
      50% of patients using current guidelines. Further, when studies are suitable for
      assessment, widely used guidelines yield discordant results.

PMID- 29178213
TI  - Interprofessional collaboration between junior doctors and nurses in the general
      ward setting: A qualitative exploratory study.
AB  - AIM: To explore the collaboration experiences of junior physicians and nurses in
      the general ward setting. BACKGROUND: Junior physicians and nurses do not always
      work collaboratively and this could affect the quality of patient care. The
      understanding of the issues affecting junior physicians and nurses working
      together is needed to inform strategies to improve interprofessional
      collaboration. METHODS: Nineteen junior physicians and nurses were interviewed in
      2012 and 2013. Interviews were transcribed and analysed using thematic analysis.
      RESULTS: Junior physicians and nurses acknowledged the importance of working
      collaboratively to achieve better patient care, but they are struggling to cope
      due to heavy clinical workload, organisational constraints and differing power
      relationships. Nurses have to take on more responsibilities in the decision
      making process of patients' care to foster effective interprofessional
      collaboration. CONCLUSION: The study calls for educational and organisational
      strategies to improve interprofessional collaboration between junior physicians
      and nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse leaders should ensure that
      ward nurses are given a designated time to participate in ward rounds with
      physicians and have access to a communication tool that assists them in
      contributing proactively in the decision-making process of patient care.

PMID- 29178214
TI  - Redox Mediators for Li-O2 Batteries: Status and Perspectives.
AB  - Li-O2 batteries have received much attention due to their extremely large
      theoretical energy density. However, the high overpotentials required for
      charging Li-O2 batteries lower their energy efficiency and degrade the
      electrolytes and carbon electrodes. This problem is one of the main obstacles in
      developing practical Li-O2 batteries. To solve this problem, it is important to
      facilitate the oxidation of Li2 O2 upon charging by using effective
      electrocatalysis. Using solid catalysts is not too effective for oxidizing the
      electronically isolating Li-peroxide layers. In turn, for soluble catalysts, red
      ox mediators (RMs) are homogeneously dissolved in the electrolyte solutions and
      can effectively oxidize all of the Li2 O2 precipitated during discharge. RMs can
      decompose solid Li2 O2 species no matter their size, morphology, or thickness and
      thus dramatically increase energy efficiency. However, some negative side
      effects, such as the shuttle reactions of RMs and deterioration of the Li-metal
      occur. Therefore, it is necessary to study the activity and stability of RMs in
      Li-O2 batteries in detail. Herein, recent studies related to redox mediators are
      reviewed and the mechanisms of redox reactions are illustrated. The development
      opportunities of RMs for this important battery technology are discussed and
      future directions are suggested.

PMID- 29178215
TI  - Transfemoral transcatheter aortic valve replacement with a self-expanding valve
      for severe aortic regurgitation in a patient with left ventricular assist device.
AB  - Aortic insufficiency following left ventricular assist device implantation (LVAD)
      has been reported in up to 40% of patients and is associated with a worse
      prognosis. We describe the case of a successful transfemoral transcatheter aortic
      valve replacement with a self-expanding bioprosthesis for aortic insufficiency
      following destination LVAD implantation.

PMID- 29178217
TI  - Conformers of Saturated Chains: Matrix Isolation, Structure, IR and UV Spectra of
      n-Si4 Me10.
AB  - Infrared and ultraviolet spectra of the gauche and anti conformers of matrix
      isolated permethyl-n-tetrasilane have been obtained separately by taking
      advantage of thermally induced gauche-to-anti conversion and of wavelength
      selective photochemical destruction of either conformer. The resolved UV spectrum
      of the gauche conformer provides the first piece of experimental evidence in
      favor of the recently proposed reinterpretation of conformational effects on
      tetrasilane electronic states. According to this, it is not the energy but the
      intensity of the lowest singlet excitation that changes dramatically as the
      SiSiSiSi dihedral angle is varied, as a result of an avoided crossing between ss*
      and spi* states. Implications for the general understanding of sigma conjugation
      in simple terms are discussed. Unconstrained MP2/6-31 G* optimization predicts
      the existence of a third backbone conformer (ortho), with a dihedral angle of
      about 90 degrees . Its predicted (HF/3-21 G*) mid-IR spectrum is
      indistinguishable from that of the gauche conformer, and the matrix-isolation
      spectra thus provide no evidence for or against its presence.

PMID- 29178216
TI  - Diagnostic utility of surgical lung biopsies in elderly patients with
      indeterminate interstitial lung disease.
AB  - BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is increasingly
      diagnosed by clinical and computed tomography (CT) criteria; however, surgical
      lung biopsy (SLB) may still be required in patients who lack definite CT features
      of usual interstitial pneumonia (UIP). We reviewed a cohort of elderly patients
      who underwent SLB, to evaluate the benefit of SLB in diagnosing idiopathic
      interstitial pneumonia (IIP). METHODS: We searched the pathology records of Mayo
      Clinic for ambulatory patients at least 75 years old, who underwent SLB between
      2000 and 2012 for indeterminate IIP. Histologic slides were reviewed and clinical
      data were extracted from the record. RESULTS: A total of 55 patients (35 male)
      were enrolled. Median (interquartile range) age was 77 (76-80) years. Forced
      vital capacity was 70 (61-76)% and diffusing capacity of the lungs for carbon
      monoxide was 48 (42-54)% of predicted. In total, 37 (67%) patients had IPF,
      including 61% of those with HRCT findings inconsistent with UIP. Thirty-day
      mortality was 10% and 90-day mortality was 15%. CONCLUSION: The high mortality
      rate of SLB complicates the risk-benefit analysis in elderly patients with IIP.
      The expected value of the SLB is probably highest when the HRCT features are
      inconsistent with UIP, due to the frequent (39%) retrieval of patterns other than
      UIP.

PMID- 29178218
TI  - Supramolecular Motifs: Concerted Multiple Phenyl Embraces between Ph4 P+ Cations
      Are Attractive and Ubiquitous.

PMID- 29178219
TI  - Coordination and Coupling of OH-Functionalized C2 Units at a Single Metal Center:
      The Synthesis of Alkynyl(Vinylidene), Alkynyl(Enyne), Bis(Alkynyl)Hydrido,
      Enynyl, and Hexapentaene Rhodium Complexes from Propargylic Alcohols as
      Precursors.
AB  - The reaction of [Rh(eta3 -C3 H5 )-(PiPr3 )2 ] (1) with HC?C?CH(Ph)OH yields the
      alkynyl(vinylidene) complex trans-[Rh{C?C?CH(Ph)OH}{?C?CH-CH(Ph)OH}(PiPr3 )2 ]
      (2), while from 1 and HC?C?CPh2 OH the alkynyl-(enyne)metal derivative trans
      [Rh(C?C?CPh2 OH){n2 -(E)-Ph2 (OH)C?C?C?CH?CH-CPh2 OH} (PiPr3 )2 ] (3) is
      obtained. On treatment with 1-alkyn-3-ols HC?C?CR2 OH (R = Me, Ph, iPr), the
      highly reactive pi-benzyl compound [Rh(n3 -CH2 Ph)(PiPr3 )2 ] (4) yields the five
      coordinate complexes [RhH(C?C?CR2 OH)2 (PiPr3 )2 ] (5-7) of which those with R =
      Me and Ph can be converted to the alkynyl(vinylidene)metal isomers trans
      [Rh(C?C?CR2 OH)(?C?CH-CR2 OH)-(PiPr3 )2 ] (8, 9). Compounds 8 and 9 react with L'
      = CO and isocyanides by migration of the alkynyl ligand to the vinylidene unit to
      give the enynylrhodium(I) complexes trans-[Rh{n1 -(Z)-C(C?C?CR2 ?OH)?CH-CR2
      OH}(L')(PiPr3 )2 ] (10, 11: L' = CO; 12-15: L' = CNR'). Cleavage of the Rh-C s
      bond of 10 with CF3 -CO2 H affords trans-[Rh(n1 -O2 CCF3 )-(CO)(PiPr3 )2 ] (16)
      and the enyne (E)-Me2 (OH)C?C?C?CH?CH-CMe2 OH (17). Compounds 5-7 react with L' =
      CO and isocyanides to give the octahedral 1:1 adducts [RhH(C?C?CR2 OH)2 (L')(P
      iPr3 )2 ] (18-20 and 24-27), of which the CO derivatives 18-20 readily eliminate
      HC?C?CR2 OH to yield trans-[Rh-(C?C?CR2 OH)(CO)(PiPr3 )2 ] (21-23). On treatment
      of 6 or 9 (R = Ph) with Al2 O3 in the presence of chloride ions, besides trans
      [RhCl(?C?C?CPh2 )(P-iPr3 )2 ] (28) the hexapentaenerhodium(I) complex trans
      [RhCl(n2 -Ph2 C?C?C?C?C?CPh2 )(PiPr3 )2 ] (29) is formed. The kinetically
      preferred isomer trans-[RhCl(n2 -Ph2 C?C?C?C?C?CPh2 )(P-iPr3 )2 ] (33) has been
      prepared from [RhCl(PiPr3 )2 ]2 and Ph2 C?C?C?C?C?CPh2 ; it rearranges smoothly
      at room temperature to the thermodynamically more stable isomer 29. The molecular
      structures of 7 and 29 have been determined.

PMID- 29178220
TI  - Stabilization of Octahedral Thorium Clusters by Interstitial Hydrogen.
AB  - The synthesis, structure, and characterization of the cluster compounds Th6 Hx
      Br15 (x = 5 and 7) are reported. The compounds can be prepared by a reversible
      hydrogenation/dehydrogenation process; their structures have been determined by X
      ray and neutron diffraction methods. Both compounds form a body-centered cubic
      structure of octahedral cluster units with five or seven hydrogen atoms in eight
      disordered positions above the faces of the octahedron. The chemical bonding in
      these diamagnetic compounds has been analyzed: the simple counting rules for
      octahedral cluster compounds are fulfilled, and MO and band structure
      calculations confirm the hydridic nature of the bonding.

PMID- 29178221
TI  - Nucleophilic Addition of Secondary Phosphines to Cationic Dienyl Tricarbonyliron
      Complexes: A novel Route to Optically Active Phosphines.
AB  - Secondary phosphines such as HPPh2 and to the cationic iron dienyl complex [eta5 
      (1R)-ethylnopadienyl)Fe-(CO)3 ]+ (1) by nucleophilic addition. The phosphonium
      salt initially formed is readily deprotonated to yield an optically active
      tertiary phosphine [(n4 -(1 R)-ethylnopadienePPh2 )Fe(CO)3 ] (2b). A similar
      reaction also occurs with [C6 H7 Fe-(CO)3 ]+ (3) and [C7 H9 Fe(CO)3 ]+ (4) to
      give [(C6 H7 PPh2 )Fe(CO)3 ] (5) and [(C7 H9 PPh2 )Fe(CO)3 ] (6) in good yields.
      The mechanism of formation of these novel phosphines is discussed. Complex 2 b
      crystallizes in the space group P21 21 21 (no. 19); 5 crystallizes in the space
      group P21 /c (no. 14). Like other monodentate optically active phosphines, 2 b is
      capable of coordinating to transition metal complexes. It forms palladium
      complexes on reaction with [{MU-chloro(allyl)palladium}2 ] as well as with [{MU
      chloro[(N,N-dimethylamino-kN-2-methyl)phenyl-kC]palladium}2 ] (11). The latter
      reaction product crystallizes in the space group P31 (no. 144).

PMID- 29178222
TI  - Multinational Papers in the Front Row.

PMID- 29178223
TI  - Synthesis of Methyl 5'-Thio-alpha-isomaltoside via an Acyclic Monothioacetal and
      its Behavior toward Glucoamylase.
AB  - Methyl 5'-thio-alpha-isomaltoside (1), which contains the ring-sulfur analogue of
      the nonreducing glucoside of isomaltose, was synthesized from gentiobiose through
      a novel ring opening-recyclization approach. The nonreducing glucoside of per-O
      benzylated phenyl 1-thio-beta-gentiobioside underwent O-5'-C-1' bond cleavage
      with dimethyl-boron bromide and thiolacetic acid to give the acyclic
      monothioacetal 4 with the 1-thioglucopyranoside at the reducing end intact. The
      HO-5' group in 4 was inverted by a standard oxidation-reduction process with good
      efficiency. Recyclization under Mitsunobu condition allowed C-5'-S-1' bond
      formation with inversion of configuration at C-5', to give 1 after functional
      group interconversion. TLC analysis showed that 1, unlike isomaltose, was not
      hydrolyzed by glucoamylase from Rhizopus niveus. A fluorometric assay confirmed
      that the dissociation constant (Kd ) for 1 with the enzyme was 39 mM at 20
      degrees C, which is comparable with that for isomaltose. A binding assay
      involving fluorescence titration of the enzyme-1 complex with gluconolactone
      indicated that the disaccharide 1 was bound to the catalytic and noncatalytic
      subsites. Since isomaltose is known to bind only to the noncatalytic subsites,
      this result indicates a relatively high affinity of the 5-thioglucose moiety for
      the catalytic subsite.

PMID- 29178224
TI  - C-Disaccharides of Ketoses.
AB  - Reaction of gluconolactone 2 with allylmagnesium bromide at low temperatures
      afforded ketopyranose 3, which could easily be converted into open-chain ketoses
      (R)-6 and (S)-6. Their reaction with lithioacetylide 9 afforded propargylic
      alcohol derivatives (R)-10 and (S)-10, which could not be cyclized directly to
      the desired C-ketosides. They were converted by standard procedures into (R)-14
      and (S)-14 and then into dicobalthexacarbonyl complexes (R)-16 and (S)-16. A
      facile acid-catalyzed ring closure gave the desired C-ketosides (R)-18 alpha/beta
      and (S)-18alpha/beta, respectively, in different ratios. In order to demonstrate
      that removal of the protective groups and hydrogenation of the CC triple bond
      proceed smoothly, (R)-18 alpha was transformed into the deprotected target
      molecule (R)-1 alpha. For the assignment of the new chiral centers at C-2/2' and
      at C-8, (S)-18alpha was transformed into azido derivative (S)-22alpha, which
      underwent intramolecular cycloaddition to afford the spiro derivative (S)
      25alpha. Because of the conformational constraints in this molecule, unequivocal
      configurational assignment was possible with the help of NMR data.

PMID- 29178225
TI  - Emission from Zeolite-Occluded Manganese-Diimine Complexes.
AB  - Manganese complexes of 2,2'-bipyridine (bpy) and 1,10-phenantroline (phen) have
      been synthesised in the supercages of cubic NaX and NaY and in the hypercages of
      the hexagonal NaEMT faujasites. The coordination and redox chemistry were studied
      with ESCA, CA, FT-IR, FT-Raman, diffuse reflectance and emission techniques. FT
      IR/FT-Raman shows cis coordination for all complexes and a high Mn-N stretching
      frequency in the phen complexes as a result of steric constraints imposed by the
      ligand. [Mn(bpy)2 ]2+ in the different zeolites shows metal-to-ligand charge
      transfer (MLCT; at 495 nm); for [Mn(phen)2 ]2+ -NaY the MLCt is broadened owing
      to complex distortion. On MLCT excitation [Mn(bpy)2 ]2+ complexes show an
      ipsochromic shift in the emission and an increase in quantum yield with
      increasing steric restrictions imposed by the zeolite. The ipsochromic shift of
      the emission band of [Mn(phen)2 ]2+ in NaY results from the combined effect of
      the ligand field (this suggests emission from a CT state) and of coordinative
      distortion. The key factor influencing the emission properties is found to be the
      overall matrix-induced complex distortion. Cation stabilisation of the ligand
      anion affects emission indirectly. The decay times for [Mn-(bpy)2 ]2+ -NaY are in
      the millisecond range (7.5-11.5 ms). A proposed model for excitation and emission
      properties of zeolite-occluded MnII complexes involves excitation of a quartet CT
      state, intersystem crossing and subsequent emission. The enhanced stability of
      the coordination sphere in the zeolite allows complexes to luminesce from a CT
      state, which is not detected in solution. The zeolite behaves as a supramolecular
      cryptating agent, protecting complexes from photodissociation.

PMID- 29178226
TI  - Conformational Preference of 2-(Halomethyl)- and 2-(Oxymethyl)Pyridines:
      Microwave Spectrum, Ab Initio, and MM3 Studies of 2-(Fluoromethyl)Pyridine.
AB  - One single conformer was assigned from the microwave spectrum of 2
      (fluoromethyl)pyridine, investigated in the gas phase in the 26.0-39.0 GHz
      spectral region at about -10 degrees C. Its Calpha-F bond was found to be
      coplanar with the ring and anti to the N-C2 bond (syn to the C2-C3 bond). There
      was no indication in the microwave spectrum of the presence of other rotameric
      forms of the molecule. The results of the spectroscopic study were backed up by
      ab initio calculations at the MP2/6-31 G** (frozen core) level. These
      calculations predict that the assigned conformer is the only stable form of the
      molecule. The transition state was calculated to have the CH2 F group 180 degrees
      from the stable anti conformation. The energy of the transition state was
      computed to be 20.2 kJ mol-1 higher than the energy of the anti rotamer. The
      results are interpreted in terms of a stereoelectronic effect, and the orbital
      overlaps responsible for the observed effect are discussed. It is shown that 2
      (fluoromethyl)pyridine serves as a good model for 2-(alkoxymethyl)pyridines,
      previously found to show the same conformational preference.

PMID- 29178227
TI  - [Lithium tert-butylperoxide]12 : Crystal Structure of an Aggregated Oxenoid.
AB  - The X-ray crystal structure of the dodecameric lithium tert-butylperoxide [2]12
      is the first of an alkali or alkaline earth peroxide. It shows the lithium ion
      bridging the two oxygen atoms of the peroxide unit and a slight lenghtening of
      the O-O bond, in agreement with quantum-chemical calculations. A calculation for
      the model reaction of MeLi with LiOOH to give MeOLi and LiOH reveals the
      importance of Li bridging the O-O bond in the transition state of this reaction,
      as similarly discussed for many oxidation reactions of (transition-) metal
      peroxides. Preliminary theoretical studies of the O-O bond length (and thus of
      the oxenoid character) as a function of the aggregation of 2 disclose that
      increasing aggregation leads to stabilization of the charge at the anionic oxygen
      atom and thus to a reduction of the O-O bond length (oxenoid character). Related
      considerations of the effect of aggregation should also be valid for other
      lithium (organometallic) compounds and their structure and reactivity as well as
      other properties.

PMID- 29178228
TI  - Versatile Synthesis of Enantiomerically Pure 2-Alkoxy-1-Ethynylcyclopropanes and
      their Application in the Synthesis of Enantiomerically Pure Bicyclo-[3.3.0]oct-1
      en-3-ones.
AB  - A variety of chiral, nonracemic 2-alkoxy-1-alkynylcyclopropanes 7 were
      synthesized in good to very good yields from enantiomerically pure glycidol
      derivatives (glycidol tosylate, epichlorohydrin) by boron trifluoride promoted
      addition of lithium trimethylsilylacetylide followed by protection of the
      secondary hydroxyl group and finally a diastereoselective gamma-elimination. The
      2-ethoxy derivative (S,R)-7 b was deprotonated with n-butyllithium, and the
      resulting 1-lithio-2-ethoxy derivative (S,R)-20 functionalized by treatment with
      oxygen followed by tosyl chloride. Protodesilylation and catalytic hydrogenation
      smoothly furnished 1-ethenylcyclopropyl sulfonates, which underwent a clean Pd0 
      catalyzed SN 2'-type substitution with dimethyl propargylsodiummalonate to give
      the (E)-configurated enyne (R,E)-26 with a methylenecyclopropane end group. A
      diastereoselective Pauson-Khand reaction completed the sequence to give the
      enantiomerically pure spirocyclopropaneannelated bicyclo[3.3.0]octane derivative
      31.

PMID- 29178229
TI  - Ionic Fluorination of Carbon Monoxide as a Route to Gasphase Carbonylation of
      Inert C?H and N?H Bonds.
AB  - Gaseous FCO+ ions from the ionization of mixtures of nitrogen trifluoride and
      carbon monoxide execute selective and efficient CO-functionalization of the C-H
      bonds of benzene and toluene and of the N-H bond of ammonia. The occurrence of
      these carbonylation reactions has been unambiguously ascertained by Fourier
      transform ion cyclotron resonance (FT-ICR) spectrometry, and the details of the
      structure and the mechanism of formation of the precursor FCO+ ions have been
      investigated. FT-ICR experiments show that these ions, structurally assigned as F
      C-O+ by collisionally activated dissociation (CAD) spectrometry, arise from the
      reaction of CO.+ with NF3 and of NF+2 with CO. Combining the latter F+ transfer
      with the independently observed fluoride-ion abstraction by FCO+ from NF3 results
      in a catalytic cycle in which gaseous NF+2 ions promote the conversion of carbon
      monoxide into carbonic difluoride, F2 CO, with nitrogen trifluoride as the source
      of F.

PMID- 29178230
TI  - Synthetic Cyclic Oligosaccharides-Syntheses and Structural Properties of a
      Cyclo[(1 -> 4)-alpha-L-rhamnopyranosyl-(1 -> 4)-alpha-D-mannopyranosyl]trioside
      and -tetraoside.
AB  - An efficient polycondensation-cyclization approach to the synthesis of
      cyclodextrin analogues is demonstrated by the preparation of cyclohexaoside 1 and
      cyclooctaoside 2. The key intermediate, disaccharide 3, bearing the
      cyanoethylidene group as a glycosyl donor function and the trityloxy group as a
      glycosyl acceptor function was prepared in 15 steps starting from L-rhamnose and
      D-mannose. The crucial cyclooligomerization of the disaccharide monomer 3 was
      carried out in the presence of TrClO4 as a promoter with the use of ultra-dry
      conditions at normal concentrations. This reaction led to formation of the cyclic
      oligosaccharides 28 and 29 (in 34 and 31% yield, respectively), which were
      deprotected to afford 1 and 2, respectively. The X-ray crystal structural
      analysis of the cyclooctaoside 2 reveals a cylindrical shape for the cyclic
      oligosaccharide with C4 symmetry. Individual molecules of 2 are arranged
      perfectly in stacks that form nanotubes in the solid state.

PMID- 29178231
TI  - O-Atom Transfer to Fe+n Clusters (n = 2-10) from O2 , N2 O and CO2 : "Microoxides
      of Iron".
AB  - We report on the gas phase reactions of small Fe+n clusters (n = 2-10) with O2 ,
      N2 O and CO2 in an FT-ICR mass spectrometer. Under our experimental conditions,
      clusters of all sizes reacted readily with O2 and all but the dimer reacted with
      N2 O. Only the smallest Fe+n clusters (n = 2-4) appeared to activate CO2 . For
      all X-O molecules (X = O, N2 , CO), reaction pathways were observed that include
      the transfer of O atoms. In addition, the reactions with O2 and N2 O were
      accompanied by the loss of one or two Fe atoms. Thermochemical considerations
      based upon the well-known X-O bond energies were used to calculate Fen -O+ bond
      dissociation energies (BDEs) for sizes n = 2-6; these amount to roughly 550 kJ
      mol-1 and thus are considerably higher than the BDE of the Fe-O+ ion. All
      oxidation reactions of the Fe+n clusters (n = 2-6) studied in more detail were
      terminated by products of Fex Ox+ stoichiometry (x = 1-4). These "microoxides of
      iron" are not able to activate any further X-O bonds. Secondary reactions of Fex
      Ox+ clusters with C6 H6 , C2 H4 and NH3 were investigated for two selected sizes
      (x = 2, 3) and compared with reactions of the naked Fe+n clusters.

PMID- 29178232
TI  - Separation of Diastereomeric and Enantiomeric Alkyl Nitrates-Systematic Approach
      to Chiral Discrimination on Cyclodextrin LIPODEX-D.
AB  - High-resolution gas chromatographic separation of all diastereomeric monomethyl
      substituted cyclohexyl nitrates is shown on a nonpolar methylpolysiloxane
      stationary phase, and the first application of this procedure to the
      environmental diastereomeric analysis of alkyl nitrates is presented. Two
      characteristic signals in the achiral analysis of atmospheric samples could be
      assigned to the smallest alkyl nitrate containing two asymmetric carbon atoms, 3
      methyl-2-pentyl nitrate. Retention indices in the temperature-programmed
      separation based on the n-alkanes were determined. The homologous series of 1
      alkyl nitrates were found to be useful as ECD-visible n-alkanes. Enantiomeric
      separation of alkyl nitrates was achieved on heptakis(3-O-acetyl,-2,6-di-O
      pentyl)-beta-cyclodextrin (LIPODEX-D). The influence of the nitrooxy group and
      the alkyl chain length on the chiral discrimination on LIPODEX-D is discussed for
      25 chiral alkyl nitrates. The absolute configurations of some alkyl nitrates were
      assigned by asymmetric synthesis of enantiomerically pure references. The
      complexity of the alkyl nitrate mixtures present in air samples does not allow a
      direct chiral separation as the alkyl nitrates partly coelute on the LIPODEX-D
      column. Column coupling of LIPODEX-D with a polar achiral stationary phase like
      polyalkylenglycol (PAG) was successfully applied to solve this problem, and the
      chiral alkyl nitrates present in a typical air sample were separated. A
      systematic nomenclature for alkyl nitrates is introduced to handle the steadily
      growing number of branched and long-chain alkyl nitrates detected in
      environmental analysis.

PMID- 29178233
TI  - Electron-poor 2,3-Dihydro-1,3-Diborolyl Complexes of Iron and Ruthenium:
      Synthesis, Reactivity, and Crystal and Electronic Structures of an Iron Sandwich
      Complex.
AB  - The addition product of sodium hydride and the 2,3-dihydro-1,3-diborole (CiPr)2
      (BEt)2 CHMe (3c) reacted with [{(C5 Me5 )FeCl}x ] to produce the green sandwich
      complex [(C5 Me5 )Fe{n5 -(CiPr)2 (BEt)2 CMe}] (2 c), which formally contains 16
      valence electrons (VE). Complex 2c has unexpected structural properties in the
      solid state: the 1,3-diborolyl ring is extremely folded (41 degrees ), and the Fe
      C2 distance is short (1.90 A). Analogously, violet Ru complexes 4a,c,d were
      obtained from 3a,c, NaH or tBuLi, and [{(C5 Me5 )RuCl}4 ]. With the less bulky
      heterocycles 3 b,e the new 30 VE triple-decker complexes [(C5 Me5 )Ru{MU,n5 -(CR1
      )2 (BR2 )2 CMe}RuH(C5 Me5 )] (5b,e) were formed, which contain a Ru-H bond.
      Cyclic voltammetric studies revealed the existence of stable anions 2c- and 4d-
      formed by reversible one-electron reduction at -1.26 and -1.40 V, respectively
      (vs. SCE). The red-brown anions were further characterized by ESR spectroscopy
      following stepwise reduction of the neutral species with potassium in THF.
      Addition of CO to 4a and 4d led to formation of the monocarbonyl complexes [(C5
      Me5 )Ru(CO){n5 -(CR1 )2 -(BR2 )2 CMe}] (6a,d), and 6d was characterized by X-ray
      structure analysis. The heterocycle in 6d is less folded (19 degrees ) than in 2
      c. Its CO ligand causes a 28.5 degrees  tilt of the cyclic ligands. Reaction of
      CO with 2 c yielded a red product of unknown structure. The electronic structure
      of 2 was studied by EH-MO theory, which revealed a unique bonding in the
      sandwich. The s electron density of the B-C bonds participates in the bonding to
      the iron atom; this demonstrates that the number of bonding electrons is the same
      as in ferrocene. Thus, the complexes 2 actually have 18 VE.

PMID- 29178234
TI  - The Pagodane -> Dodecahedrane Concept-Shorter Routes, Higher Yields.
AB  - Two variants of the "SN 2 route" from pagodanes (A, B) to functionalized
      dodecahedranes (D, F) and particularly dodecahedradienes (E) offer considerable
      improvements in the number of operations (from nine to five to three) and yields
      (e.g., for diester F from 55-65 to 70-75 to 85-91%). Key steps are the regio- and
      stereospecific introduction of four to six bromine substituents into dimethyl
      pagodane-4-syn,9-syn-dicarboxylate (1 b) and a highly complex (thirteen bond
      breaking/bond-forming events in four participating structures). yet very
      convenient (one-pot operation) and extremely efficient (nearly quantitative)
      transformation of secopagodane to bissecododecahedradiene with complete
      stereocontrol in transannular CH2 functionalizations. The prohibitively low
      kinetic acidity of "caged" hydrogens has so far only been overcome with the
      recently reported P2 F reagent (Schwesinger). Further improvement of the overall
      economy of the pagodane -> dodecahedrane scheme has been achieved by efficiently
      channeling a byproduct of the pagodane synthesis (ca. 10%) back into the SN 2
      track.

PMID- 29178235
TI  - Validation of a simultaneous method for determining polycyclic aromatic compounds
      and alkylated isomers in biota.
AB  - RATIONALE: There is a need for a validated method to improve detection limits and
      simultaneously quantify polycyclic aromatic compounds (PACs, both parent and
      alkylated homologues) in biota by gas chromatography/tandem mass spectrometry
      because of their environmental significance. The validation of the method was
      performed in accordance to the Eurachem Guide to Quality in Analytical Chemistry.
      METHODS: Gas chromatography coupled with a triple quadrupole mass spectrometer
      used in multiple reaction monitoring (MRM) mode was used for detection and
      quantification. Retention time windows and selective MRM ion transitions were
      optimized for a suite of PACs. The developed method was validated by comparing
      our measurements made on a reference material of freeze-dried mussel tissue
      (Mytilus edulis) with the certified values. RESULTS: Linearity was observed
      between 10-1000 pg/MUL (PAHs) and 2-500 pg/MUL (alkyl-PACs including S-based
      PACs). The overall mean (+/-SD) for the limits of detection of 43 PACs studied
      were 0.305 +/- 0.276 and 2.69 +/- 1.10 ng/g, respectively. For the 14 certified
      target analytes, the percent relative error ranged from 1.3 to 33%. With the
      exception of benzo(a)pyrene, the between-day and within-day repeatability for all
      target analytes was lower than 15% RSD. CONCLUSIONS: This is the first report of
      a fully validated method to simultaneously quantify PACs in biota performed in an
      ISO accredited laboratory.

PMID- 29178236
TI  - Prevalence, predictors and challenges of gestational diabetes mellitus screening
      among pregnant women in northern Tanzania.
AB  - OBJECTIVES: To determine the prevalence and predictors of gestational diabetes
      mellitus (GDM) as well as acceptability of returning for glucose tolerance
      testing among pregnant women in Moshi municipality, northern Tanzania. METHODS:
      Cross-sectional study from October 2015 to April 2016 among women with gestation
      age of 24-28 weeks of pregnancy attending at Kilimanjaro Christian Medical Centre
      (KCMC) referral hospital, Majengo and Pasua Health Centres. Women were
      interviewed and requested to return the next day (window within a month,
      depending on gestational age) for fasting plasma glucose (FPG) testing, followed
      immediately by a 75 g oral glucose tolerance test (OGTT). GDM was diagnosed using
      the 2013 WHO criteria. Logistic regression was conducted to reveal independent
      predictors for GDM. RESULTS: Of 433 interviewed women, 100 (23%) did not return
      for FPG and OGTT testing. The prevalence of GDM among the 333 screened women was
      19.5%, and 3% had diabetes in pregnancy (DIP). GDM was significantly associated
      with age >=35 years (adjusted OR 6.75), pre-pregnancy obesity (AOR 2.22) and
      history of abortion (AOR 2.36). CONCLUSION: Prevalence of GDM is high in Moshi.
      We recommend introduction of routine screening for hyperglycaemia during
      pregnancy along with strategies for follow-up to prevent long-term effects of GDM
      and DIP in women and their children.

PMID- 29178237
TI  - Cholesterol and desmosterol dancing to the beat of a different drug.

PMID- 29178238
TI  - Intergenerational effects of nutrition on immunity: a systematic review and meta
      analysis.
AB  - Diet and immunity are both highly complex processes through which organisms
      interact with their environment and adapt to variable conditions. Parents that
      are able to transmit information to their offspring about prevailing
      environmental conditions have a selective advantage by 'priming' the physiology
      of their offspring. We used a meta-analytic approach to test the effect of
      parental diet on offspring immune responses. Using the geometric framework for
      nutrition (a method for analysing diet compositions wherein food nutrient
      components are expressed as axes in a Cartesian coordinate space) to define
      dietary manipulations in terms of their energy and macronutrient compositions, we
      compiled the results of 226 experiments from 38 published papers on the
      intergenerational effects of diet on immunity, across a range of study species
      and immunological responses. We observed intergenerational impacts of parental
      nutrition on a number of offspring immunological processes, including expression
      of pro-inflammatory biomarkers as well as decreases in anti-inflammatory markers
      in response to certain parental diets. For example, across our data set as a
      whole (encompassing several types of dietary manipulation), dietary stress in
      parents was seen to significantly increase pro-inflammatory cytokine levels
      measured in offspring (overall d = 0.575). All studies included in our analysis
      were from experiments in which the offspring were raised on a normal or control
      diet, so our findings suggest that a nutrition-dependent immune state can be
      inherited, and that this immune state is maintained in the short term, despite
      offspring returning to an 'optimal' diet. We demonstrate how the geometric
      framework for nutrition can be used to disentangle the role that different forms
      of dietary manipulation can have on intergenerational immunity. For example,
      offspring B-cell responses were significantly decreased when parents were raised
      on a range of different diets. Similarly, our approach allowed us to show that a
      parental diet elevated in protein (regardless of energy composition and relative
      to a control diet) can increase expression of inflammatory markers while
      decreasing B-cell-associated markers. By conducting a systematic review of the
      literature, we have identified important gaps that impair our understanding of
      the intergenerational effects of diet, such as a paucity of experimental studies
      involving increased protein and decreased energy, and a lack of studies directed
      at the whole-organism consequences of these processes, such as immune resilience
      to infection. The results of our analyses inform our understanding of the effects
      of diet on physiological state across diverse biological fields, including
      biomedical sciences, maintenance of agricultural breed stock and conservation
      breeding programs, among others.

PMID- 29178239
TI  - Communities mobilizing for change on alcohol (CMCA): secondary analyses of a
      randomized controlled trial showing effects of community organizing on alcohol
      acquisition by youth in the Cherokee nation.
AB  - AIMS: We evaluated the effects of a community organizing intervention,
      Communities Mobilizing for Change on Alcohol (CMCA), on the propensity of retail
      alcohol outlets to sell alcohol to young buyers without age identification and on
      alcohol acquisition behaviors of underage youth. DESIGN: Random assignment of
      community to treatment (n = 3) or control (n = 2). Student surveys were conducted
      four times per year for 3 years; the cohort was in 9th and 10th grades in the
      2012-13 academic year. Alcohol purchase attempts were conducted every 4 weeks at
      alcohol retailers in each community (31 repeated waves). SETTING: The Cherokee
      Nation, located in northeastern Oklahoma, USA. PARTICIPANTS: A total of 1399 high
      school students (50% male; 45% American Indian) and 113 stores licensed to sell
      alcohol across five study communities. INTERVENTION: Local community organizers
      formed independent citizen action teams to advance policies, procedures and
      practices of local institutions in ways to reduce youth access to alcohol and
      foster community norms opposed to teen drinking. MEASUREMENTS: Perceptions
      regarding police enforcement and perceived difficulty of and self-reported actual
      acquisition of alcohol from parents, adults, peers and stores. FINDINGS: Alcohol
      purchases by young-appearing buyers declined significantly, an 18 [95% confidence
      interval (CI) = 3, 33] percentage-point reduction over the intervention period.
      Student survey results show statistically significant differences in the
      trajectory of perceived police enforcement, increasing 7 (4, 10) percentage
      points, alcohol acquisition from parents, decreasing 4 (0.1, 8) percentage
      points, acquisition from 21+ adults, decreasing 6 (0.04, 11) percentage points,
      from < 21 peers decreasing 8 (3, 13) percentage points and acquisition from
      stores decreasing 5 (1, 9) percentage points. CONCLUSIONS: A community organizing
      intervention, Communities Mobilizing for Change on Alcohol (CMCA), is effective
      in reducing the availability of alcohol to underage youth in the United states.
      Furthermore, results indicate that the previously reported significant effects of
      CMCA on teen drinking operate, at least in part, through effects on alcohol
      access.

PMID- 29178240
TI  - Post-Operative Localization of Deep Brain Stimulation Electrodes in the
      Subthalamus Using Transcranial Sonography.
AB  - OBJECTIVES: The correct positioning of deep brain stimulation electrodes
      determines the success of surgery. In this study, we attempt to validate
      transcranial sonography (TCS) as a method for early postoperative confirmation of
      electrode location in the subthalamic nucleus (STN). MATERIALS AND METHODS:
      Nineteen patients diagnosed with Parkinson's disease were enrolled in the study.
      Postoperative TCS was applied to measure the distance between the implanted
      electrodes and the third ventricle in the axial plane. Whether the electrodes
      were positioned within or outside the substantia nigra (SN) was evaluated through
      measurements in the coronal plane. The obtained metrics through TCS were compared
      with those from postoperative computed tomography (CT) and magnetic resonance
      imaging (MRI). RESULTS: A statistically significant correlation between distances
      from electrode to third ventricle by TCS and CT/MRI (r = 0.75, p < 0.01) was
      observed. Distances from third ventricle to electrodes tips were different when
      sonographically they showed to be inside or outside the SN (p < 0.01). A cut-off
      value of 8.85mm in these distances was the most sensitive (100%) and specific
      (90.5%) to predict if electrodes were positioned inside the SN (CI 95% 0.81
      10.30, p = 0.001). CONCLUSIONS: Transcranial sonography is a useful technique to
      reliably identify targeted positioning of deep brain stimulation electrodes in or
      out of the SN.

PMID- 29178241
TI  - Rare FMR1 gene mutations causing fragile X syndrome: A review.
AB  - Fragile X syndrome (FXS) is the most common inherited form of intellectual
      disability, typically due to CGG-repeat expansions in the FMR1 gene leading to
      lack of expression. We identified a rare FMR1 gene mutation (c.413G>A),
      previously reported in a single patient and reviewed the literature for other
      rare FMR1 mutations. Our patient at 10 years of age presented with the classical
      findings of FXS including intellectual disability, autism, craniofacial findings,
      hyperextensibility, fleshy hands, flat feet, unsteady gait, and seizures but
      without the typical CGG-repeat expansion. He had more features of FXS than the
      previously reported patient with the same mutation. Twenty individuals reported
      previously with rare missense or nonsense mutations or other coding disturbances
      of the FMR1 gene ranged in age from infancy to 50 years; most were verbal with
      limited speech, had autism and hyperactivity, and all had intellectual
      disability. Four of the 20 individuals had a mutation within exon 15, three
      within exon 5, and two within exon 2. The FMR1 missense mutation (c.413G>A) is
      the same as in a previously reported male where it was shown that there was
      preservation of the post-synaptic function of the fragile X mental retardation
      protein (FMRP), the encoded protein of the FMR1 gene was preserved. Both patients
      with this missense mutation had physical, cognitive, and behavioral features
      similarly seen in FXS.

PMID- 29178242
TI  - Deceased organ donor screening for human immunodeficiency virus, hepatitis B
      virus and hepatitis C virus: Discordant serology and nucleic acid testing
      results.
AB  - BACKGROUND: Before the 2014 policy change pertaining to infectious disease
      screening, many organ procurement organizations (OPOs) were supplementing
      serologic screening of deceased organ donors with nucleic acid testing (NAT) for
      human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and hepatitis C
      virus (HCV). The number of seronegative, NAT-positive donors has not been
      directly measured. METHODS: HIV, HBV, and HCV screening results of 11 229 donor
      referrals evaluated from 2010 to 2013 were obtained from 3 OPO-affiliated
      laboratories, capturing 35% of all donors in the United States. Laboratories used
      either polymerase chain reaction assay or transcription-mediated amplification
      assay to test 9643 deceased donors by NAT. RESULTS: The NAT results were positive
      in 21 (0.2%), 1 (0.02%), and 11 (0.1%) donors who were seronegative for HIV, HBV,
      and HCV, respectively. All discordant HIV-1 results were from one laboratory
      using a polymrease chain reaction assay. Thirteen of the reactive HIV NAT results
      in seronegative referrals were repeated and were non-reproducibly positive (NRP).
      Ten (0.1%), 452 (7.8%), and 197 (2.2%) of HIV-, HBV-, and HCV-seropositive
      donors, respectively, were negative by NAT. CONCLUSIONS: This study highlights
      the importance of robust quality assurance to minimize NRP NAT results. NAT may
      allow for increased utilization of organs from HBV- and HCV-seropositive, NAT
      negative donors.

PMID- 29178243
TI  - Probing the limits of predictability: data assimilation of chaotic dynamics in
      complex food webs.
AB  - The daunting complexity of ecosystems has led ecologists to use mathematical
      modelling to gain understanding of ecological relationships, processes and
      dynamics. In pursuit of mathematical tractability, these models use simplified
      descriptions of key patterns, processes and relationships observed in nature. In
      contrast, ecological data are often complex, scale-dependent, space-time
      correlated, and governed by nonlinear relations between organisms and their
      environment. This disparity in complexity between ecosystem models and data has
      created a large gap in ecology between model and data-driven approaches. Here, we
      explore data assimilation (DA) with the Ensemble Kalman filter to fuse a two
      predator-two-prey model with abundance data from a 2600+ day experiment of a
      plankton community. We analyse how frequently we must assimilate measured
      abundances to predict accurately population dynamics, and benchmark our
      population model's forecast horizon against a simple null model. Results
      demonstrate that DA enhances the predictability and forecast horizon of complex
      community dynamics.

PMID- 29178244
TI  - Status of tuberculosis-related stigma and associated factors: a cross-sectional
      study in central China.
AB  - OBJECTIVES: Tuberculosis (TB) poses a significant challenge to public health
      worldwide. Stigma is a major obstacle to TB control by leading to delay in
      diagnosis and treatment non-adherence. This study aimed to evaluate the status of
      TB-related stigma and its associated factors among TB patients in China. METHODS:
      Cross-sectional survey. Thus, 1342 TB patients were recruited from TB
      dispensaries in three counties in Hubei Province using a multistage sampling
      method and surveyed using a structured anonymous questionnaire including
      validated scales to measure TB-related stigma. A generalised linear regression
      model was used to identify the factors associated with TB-related stigma.
      RESULTS: The average score on the TB-related Stigma Scale was 9.33 (SD = 4.25).
      Generalised linear regression analysis revealed that knowledge about TB (beta = 
      0.18, P = 0.0025), family function (beta = -0.29, P < 0.0001) and doctor-patient
      communication (beta = -0.32, P = 0.0005) were negatively associated with TB
      related stigma. CONCLUSIONS: TB-related stigma was high among TB patients in
      China. Interventions concentrating on reducing TB patients' stigma in China
      should focus on improving patients' family function and patients' knowledge about
      TB.

PMID- 29178245
TI  - Temperature-programmed multicapillary gas chromatograph microcolumn for the
      analysis of odorous sulfur pollutants.
AB  - We report the fabrication and performance of a silicon-on-glass micro gas
      chromatography eight-capillary column based on microelectromechanical systems
      technology that is 50 cm long, 30 MUm wide, and 300 MUm deep. According to the
      theory of a gas chromatography column, an even gas flow among different
      capillaries play a vital role in the peak broadening. Thus, a flow splitter
      structure is designed by the finite element method through the comparison of the
      velocity distributions of the eight-capillary columns with and without splitter
      as well as an open tubular column. The simulation results reveal that eight
      capillary column with flow splitters can receive more uniform flow velocity in
      different capillaries, hence decreases the peak broadening and in turn increases
      the separation efficiency. The separation experiment results show that the
      separation efficiency of about 22 000 plates/m is achieved with the chip column
      temperature programmed for analysis of odorous sulfur pollutants. This figure is
      nearly two times higher than that of the commercial capillary column coated the
      similar stationary phase. And the separation time of all the components in the
      microcolumn is less than 3.8 min, which is faster than the commercial capillary
      column.

PMID- 29178246
TI  - Effects of the antagomiRs 15b and 200b on the altered healing pattern of diabetic
      mice.
AB  - BACKGROUND AND PURPOSE: Diabetic patients with non-healing ulcers have a reduced
      expression of VEGF. Genetically diabetic mice have an altered expression pattern
      of VEGF and its receptor, VEGF receptor 2 (VEGFR-2). In diabetic wounds, the
      microRNAs, miR15b and miR200b, which respectively inhibit VEGF and VEGF-R2 mRNAs,
      are up-regulated, further affecting the impaired angiogenesis. We investigated
      whether anti-miRs directed toward miR15b and miR200b could improve wound repair
      in genetically diabetic mice. EXPERIMENTAL APPROACH: Skin wounds were produced on
      the backs of female diabetic mice. The anti-miRs (antimiR15b, antimiR200b or
      antimiR15b/200b) at 10 mg.kg-1 , or vehicle were applied to the wound edge. Mice
      were killed on days 7, 14 and at time of complete wound closure. Levels of mRNA
      and protein of angiogenic mediators and their receptors were measured with RT
      qPCR and Western blotting. Wounds were examined by histological and
      immunochemical methods. KEY RESULTS: mRNA expression of VEGF, VEGFR-2,
      angiopoietin-1 and its receptor TEK were evaluated after 7 and 14 days. Protein
      levels of VEGF and transglutaminase II were measured at day 7, while VEGFR-2 and
      Angiopoietin-1 were measured at day 14. Histological features and the time to
      achieve a complete wound closure were also examined. Treatment with the anti-miRs
      improved the analysed parameters and the co-treatment resulted the most
      effective. CONCLUSION AND IMPLICATIONS: The results suggest that the inhibition
      of miR15b and miR200b may have a potential application in diabetes-related wound
      disorders.

PMID- 29178247
TI  - Isavuconazole shortens the QTc interval.
AB  - Isavuconazole is a novel antifungal drug approved for the treatment of adults
      with invasive aspergillosis and mucormycosis. While azoles as a class effect are
      known to prolong QTc interval, clinical trials have shown that isavuconazole
      administration may cause shortening in a dose-related manner. Here, we assessed
      the effects of isavuconazole on the length of QTc interval. The objective of the
      study was to describe changes in the QTc interval induced by isavuconazole
      treatment. A total of 26 adult patients from 7 hospitals were included. Patients
      received isavuconazole for the treatment of invasive fungal infection and, in 1
      case, for prophylaxis due to QTc prolongation under fluconazole. Twelve-channel
      electrocardiograms (ECGs) were performed before and during treatment. Out of 26
      patients, 24 showed shortening of QTc interval. In patients with QTc shortening,
      QTc during isavuconazole treatment showed a mean decrease of 7.4 +/- 5.8% (36.5
      +/- 38.8 ms, range 7-202; P = .004), compared to pre-isavuconazole ECG. One
      patient with available long-term follow-up showed further decrease in QTc on days
      55 and 110. Apart from 1 case report, these are the first data outside controlled
      clinical trials showing QTc shortening. Knowledge about cardiac effects of
      isavuconazole will serve to better manage the use of concomitant medications.

PMID- 29178248
TI  - No indication of increased infection rates using low-dose alemtuzumab instead of
      anti-thymocyte globulin as graft-versus-host disease prophylaxis before
      allogeneic stem cell transplantation.
AB  - BACKGROUND: Alemtuzumab as part of the conditioning protocol is effective in
      reducing graft-versus-host disease (GvHD), but may be associated with increased
      infection rates, especially when using high doses (ie, 100 mg). METHODS: We
      performed a retrospective, single-center, case-control study analyzing the rates
      of neutropenic fever, cytomegalovirus (CMV) reactivation, Epstein-Barr virus
      (EBV) reactivation, clinical manifest toxoplasmosis, and clinical manifest human
      herpesvirus-6 (HHV6) infection using low-dose alemtuzumab in comparison with anti
      thymocyte globulin (ATG) as GvHD prophylaxis before allogeneic stem cell
      transplantation. Forty-four patients transplanted from unrelated donors between
      2001 and 2012 were matched by age, diagnosis, and conditioning regimen and
      treated either with alemtuzumab 10 mg at day -2 (respectively, 20 mg in case of
      mismatch transplantation) or ATG. ATG Fresenius (10 mg/kg for 3 days) or
      Thymoglobulin (2 mg/kg for 3 days) were used. RESULTS: Rates of CMV reactivation,
      EBV reactivation, and clinical manifest HHV6 infection or toxoplasmosis did not
      differ significantly between both groups until 2 years after transplantation. No
      case of post-transplant lymphoproliferative disorder was observed. Also, rates of
      neutropenic fever during inpatient treatment after transplantation did not differ
      significantly in both groups. CONCLUSION: We saw no indication of increased
      infections rates when using low-dose alemtuzumab as GvHD prophylaxis before
      allogeneic stem cell transplantation in this retrospective analysis.

PMID- 29178249
TI  - Validation of automated screening for referable diabetic retinopathy with the IDx
      DR device in the Hoorn Diabetes Care System.
AB  - PURPOSE: To increase the efficiency of retinal image grading, algorithms for
      automated grading have been developed, such as the IDx-DR 2.0 device. We aimed to
      determine the ability of this device, incorporated in clinical work flow, to
      detect retinopathy in persons with type 2 diabetes. METHODS: Retinal images of
      persons treated by the Hoorn Diabetes Care System (DCS) were graded by the IDx-DR
      device and independently by three retinal specialists using the International
      Clinical Diabetic Retinopathy severity scale (ICDR) and EURODIAB criteria.
      Agreement between specialists was calculated. Results of the IDx-DR device and
      experts were compared using sensitivity, specificity, positive predictive value
      (PPV) and negative predictive value (NPV), distinguishing between referable
      diabetic retinopathy (RDR) and vision-threatening retinopathy (VTDR). Area under
      the receiver operating characteristic curve (AUC) was calculated. RESULTS: Of the
      included 1415 persons, 898 (63.5%) had images of sufficient quality according to
      the experts and the IDx-DR device. Referable diabetic retinopathy (RDR) was
      diagnosed in 22 persons (2.4%) using EURODIAB and 73 persons (8.1%) using ICDR
      classification. Specific intergrader agreement ranged from 40% to 61%.
      Sensitivity, specificity, PPV and NPV of IDx-DR to detect RDR were 91% (95% CI:
      0.69-0.98), 84% (95% CI: 0.81-0.86), 12% (95% CI: 0.08-0.18) and 100% (95% CI:
      0.99-1.00; EURODIAB) and 68% (95% CI: 0.56-0.79), 86% (95% CI: 0.84-0.88), 30%
      (95% CI: 0.24-0.38) and 97% (95% CI: 0.95-0.98; ICDR). The AUC was 0.94 (95% CI:
      0.88-1.00; EURODIAB) and 0.87 (95% CI: 0.83-0.92; ICDR). For detection of VTDR,
      sensitivity was lower and specificity was higher compared to RDR. AUC's were
      comparable. CONCLUSION: Automated grading using the IDx-DR device for RDR
      detection is a valid method and can be used in primary care, decreasing the
      demand on ophthalmologists.

PMID- 29178250
TI  - Sublingual functional capillary rarefaction in chronic heart failure.
AB  - BACKGROUND AND OBJECTIVE: Microcirculatory changes contribute to clinical
      symptoms and disease progression in chronic heart failure (CHF). A depression of
      coronary flow reserve is associated with a lower myocardial capillary density in
      biopsies. We hypothesized that changes in cardiac microcirculation might also be
      reflected by a systemic reduction in capillaries and visualized by sublingual
      videomicroscopy. The aim was to study in vivo capillary density and glycocalyx
      dimensions in patients with CHF vs healthy controls. METHODS: Fifty patients with
      ischaemic and nonischaemic CHF and standard treatment were compared to 35 healthy
      age-matched subjects in a prospective cross-sectional study. Sublingual
      microcirculation was visualized using a sidestream darkfield videomicroscope.
      Functional and perfused total capillary densities were compared between patients
      and controls. A reduced glycocalyx thickness was measured by an increased
      perfused boundary region (PBR). RESULTS: Median functional and total perfused
      capillary densities were 30% and 45% lower in patients with CHF (both P < .001).
      Intake of oral vitamin K antagonists was associated with significantly lower
      capillary densities (P < .05), but not independent of NT-proBNP. Dimensions of
      the glycocalyx were marginally lower in CHF patients than in healthy controls
      (<7% difference). However, PBR correlated significantly with inflammation markers
      (fibrinogen: r = .58; C-reactive protein: r = .42), platelet counts (r = .36) and
      inversely with measures of liver/renal function such as bilirubin (r = -.38) or
      estimated glomerular filtration rate (r = -.34) in CHF patients. CONCLUSION: CHF
      patients have got a markedly lower functional and total perfused capillary
      density in sublingual microvasculature when compared to controls, indicating a
      systemic decrease in microcirculation.

PMID- 29178251
TI  - Seizure and cognitive outcomes after resection of glioneuronal tumors in
      children.
AB  - OBJECTIVE: Glioneuronal tumors (GNTs) are well-recognized causes of chronic drug
      resistant focal epilepsy in children. Our practice involves an initial period of
      radiological surveillance and antiepileptic medications, with surgery being
      reserved for those with radiological progression or refractory seizures. We
      planned to analyze the group of patients with low-grade GNTs, aiming to identify
      factors affecting seizure and cognitive outcomes. METHODS: We retrospectively
      reviewed the medical records of 150 children presenting to Great Ormond Street
      Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging,
      neuropsychological, and surgical factors was performed to determine predictors of
      outcome. Seizure outcome at final follow-up was classified as either seizure-free
      (group A) or not seizure-free (group B) for patients with at least 12-months
      follow-up postsurgery. Full-scale intelligence quotient (FSIQ) was used as a
      measure of cognitive outcome. RESULTS: Eighty-six males and 64 females were
      identified. Median presurgical FSIQ was 81. One hundred twenty-one patients
      (80.5%) underwent surgery. Median follow-up after surgery was 2 years, with 92
      patients (76%) having at least 12 months of follow-up after surgery. Seventy-four
      patients (80%) were seizure-free, and 18 (20%) continued to have seizures.
      Radiologically demonstrated complete tumor resection was associated with higher
      rates of seizure freedom (P = .026). Higher presurgical FSIQ was related to
      shorter epilepsy duration until surgery (P = .012) and to older age at seizure
      onset (P = .043). SIGNIFICANCE: A high proportion of children who present with
      epilepsy and GNTs go on to have surgical tumor resection with excellent
      postoperative seizure control. Complete resection is associated with a higher
      chance of seizure freedom. Higher presurgical cognitive functioning is associated
      with shorter duration of epilepsy prior to surgery and with older age at seizure
      onset. Given the high rate of eventual surgery, early surgical intervention
      should be considered in children with continuing seizures associated with GNTs.

PMID- 29178252
TI  - The cross-sectional associations between objectively measured sedentary time and
      cardiometabolic health markers in adults - a systematic review with meta-analysis
      component.
AB  - Sedentary time is viewed as an independent risk factor for adverse
      cardiometabolic health (CMH). No systematic review and meta-analysis on the cross
      sectional associations between objectively measured sedentary time and CMH
      markers has been conducted. PubMed, Scopus and Web of Science Core Collection
      were searched for papers that examined the cross-sectional association between
      objectively measured sedentary time and CMH markers in adults. Forty-six papers
      met the inclusion criteria. The included papers had a combined sample size of
      70,576 and an age range of 18-87 years. To examine the effect of increased levels
      of sedentary time on CMH markers, data on effect sizes and moderators were
      extracted, where possible. By pooling the unadjusted data from the included
      papers, increased sedentary time was shown to have a significant detrimental
      association with fasting glucose (Delta = 0.12, 95% confidence interval [CI]:
      0.02, 0.23), fasting insulin (Delta = 0.19, 95% CI: 0.06, 0.32), triglycerides
      (Delta = 0.25, 95% CI: 0.14, 0.37), high-density lipoprotein cholesterol (Delta =
      -0.20, 95% CI: -0.28, -0.13) and waist circumference (Delta = 0.25, 95% CI: 0.15,
      0.35). How sedentary time was quantified and the device used to measure sedentary
      time significantly influence the size of the effect reported. Future
      interventions focused on both decreasing sedentary time and increasing physical
      activity may be the most effective strategy to improve CMH.

PMID- 29178253
TI  - Kefir Peptides Prevent Hyperlipidemia and Obesity in High-Fat-Diet-Induced Obese
      Rats via Lipid Metabolism Modulation.
AB  - SCOPE: Obesity has reached epidemic proportions worldwide. Obesity is a complex
      metabolic disorder that is linked to numerous serious health complications with
      high morbidity. The present study evaluated the effects of kefir peptides on high
      fat diet (HFD)-induced obesity in rats. METHODS AND RESULTS: Kefir peptides
      markedly improved obesity, including body weight gain, inflammatory reactions and
      the formation of adipose tissue fat deposits around the epididymis and kidney,
      and adipocyte size. Treating high fat diet (HFD)-induced obese rats with kefir
      peptides significantly reduced the fatty acid synthase protein and increased the
      p-acetyl-CoA carboxylase protein to block lipogenesis in the livers. Kefir
      peptides also increased fatty acid oxidation by increasing the protein
      expressions of phosphorylated AMP-activated protein kinase, peroxisome
      proliferator-activated receptor-alpha, and hepatic carnitine palmitoyltransferase
      1 in the livers. In addition, administration of kefir peptides significantly
      decreased the inflammatory response (TNF-alpha, IL-1beta, and TGF-beta) to
      modulate oxidative damage. CONCLUSION: These results demonstrate that kefir
      peptides treatment improves obesity via inhibition of lipogenesis, modulation of
      oxidative damage, and stimulation of lipid oxidation. Therefore, kefir peptides
      may act as an anti-obesity agent to prevent body fat accumulation and obesity
      related metabolic diseases.

PMID- 29178254
TI  - Rising trends of endogenous Klebsiella pneumoniae endophthalmitis in Australia:
      comment.

PMID- 29178255
TI  - Metal-Catalyzed Synthesis and Use of Thioesters: Recent Developments.
AB  - While thioesters are common intermediates in biochemical processes, they are much
      less appreciated in organic synthesis, also compared to other carboxylic acid
      derivatives. However, their chemistry and reactivity is intriguing and
      diversified, reaching much further than the acyl substitution and aldol
      chemistry. Herein, we focus on metal-catalyzed reactions for the synthesis of
      thioesters as well as their transformations. Reactions such as thiocarbonylation,
      cross-coupling, decarbonylation, allylic substitution or dual photoredox/metal
      catalysis are discussed. On one hand, new atom economic methods allow for
      convenient synthesis of thioesters from well available starting materials. On the
      other hand, various synthetically important compounds can by synthesized due to
      the multifaceted reactivity of thioesters that we aimed to depict.

PMID- 29178256
TI  - Tuboperitoneal anomalies among infertile women in Nigeria as seen on laparoscopy.
AB  - OBJECTIVE: To study the prevalence and pattern of tuboperitoneal pathologies
      among infertile women in Nigeria, using laparoscopy. METHODS: A prospective study
      was undertaken of infertile women who underwent diagnostic laparoscopy in two
      fertility clinics in Nigeria between November 2015 and April 2017. The rates of
      identified tuboperitoneal diseases were examined. RESULTS: The age of the 230
      women ranged from 21 to 46 years, and most women had a parity group of 0-1
      (87.8%; n=202). Secondary infertility accounted for 124 (53.9%) cases, and the
      mean duration of infertility was 4.6 +/- 2.7 years. Tuboperitoneal pathologies
      were seen in 171 (74.4%) women and mainly comprised tubal occlusion (56.5%;
      n=130), hydrosalpinx (41.7%; n=96), pelvic adhesions (39.6%, n=91), and
      endometriosis (8.8%; n=19). Bilateral tubal occlusion was seen in 46 (20.0%)
      women, whereas proximal tubal occlusion accounted for 73 (56.2%) of all cases of
      tubal occlusion. CONCLUSION: There was a high rate of tuboperitoneal
      abnormalities in the studied population, which mainly comprised tubal occlusion,
      hydrosalpinx, pelvic adhesions, and endometriosis. The introduction of
      laparoscopy is recommended in the initial evaluation of all women with
      infertility in Nigeria.

PMID- 29178257
TI  - Gender-Specific Association Between ABCC2 -24C>T SNP and Reduction in
      Triglycerides in Chilean Patients Treated With Atorvastatin.
AB  - Statins are the first-line therapy prescribed to lower plasma cholesterol levels.
      Although being safe and showing several beneficial cholesterol-independent
      pleiotropic effects, a significant variability regarding statin's therapeutic
      goals has been abundantly documented, but less understood. We aimed to
      investigate the influence of the ABCC2 -24C>T single nucleotide polymorphism on
      Chilean hypercholesterolaemic individuals treated for 4 weeks with 10 mg/day
      atorvastatin. A total of 127 individuals medicated with atorvastatin 10 mg/day/4
      weeks were included. Lipid profiles were determined before and after drug
      administration by conventional assays. Genotyping of the ABCC2 rs717620 SNP (
      24C>T) was performed with TaqMan(r) Drug Metabolism Genotyping Assays. As
      expected, atorvastatin reduced TC, LDL-C and TG concentrations (p < 0.05). Also,
      HDL-C levels were increased (p < 0.05). Minor allele frequency for the rs717620
      was 0.232. Overall, atorvastatin response was not associated with the ABCC2
      rs717620 SNP (p > 0.05). Nonetheless, in male individuals carrying the -24T
      allele, we observed an attenuated reduction in both TG values and the TG/HDL-C
      ratio after 10 mg/day atorvastatin. This study indicates that TG levels and the
      TG/HDL-C ratio are affected by the rs717620 SNP in Chilean males but not female
      individuals after atorvastatin treatment.

PMID- 29178258
TI  - Feasibility analysis of early temporal kinetics as a surrogate marker for breast
      tumor type, grade, and aggressiveness.
AB  - BACKGROUND: Screening breast MRI has been shown to preferentially detect high
      grade ductal carcinoma in situ (DCIS) and invasive carcinoma, likely due to
      increased angiogenesis resulting in early initial uptake of contrast. As interest
      grows in abbreviated screening breast MRI (AB-MRI), markers of early contrast
      washin that can predict tumor grade and potential aggressiveness are of clinical
      interest. PURPOSE: To evaluate the feasibility of using the initial enhancement
      ratio (IER) as a surrogate marker for tumor grade, hormone receptor status, and
      prognostic markers, as an initial step to being incorporated into AB-MRI. STUDY
      TYPE: Retrospective. SUBJECTS: In all, 162 women (mean 55.0 years, range 32.8
      87.7 years) with 187 malignancies imaged January 2012-November 2015. FIELD
      STRENGTH/SEQUENCE: Images were acquired at 3.0T with a T1 -weighted gradient echo
      fat-suppressed-volume interpolated breath-hold sequence. ASSESSMENT: Subjects
      underwent dynamic contrast-enhanced breast MRI with a 7-channel breast coil. IER
      (% signal increase over baseline at the first postcontrast acquisition) was
      assessed and correlated with background parenchymal enhancement, washout curves,
      stage, and final pathology. STATISTICAL TESTS: Chi-square test, Spearman rank
      correlation, Mann-Whitney U-tests, Bland-Altman analysis, and receiver operating
      characteristic curve analysis. RESULTS: IER was higher for invasive cancer than
      for DCIS (R1/R2, P < 0.001). IER increased with tumor grade (R1: r = 0.56, P <
      0.001, R2: r = 0.50, P < 0.001), as ki-67 increased (R1: r = 0.35, P < 0.001; R2
      r = 0.35, P < 0.001), and for node-positive disease (R1/R2, P = 0.001). IER was
      higher for human epidermal growth factor receptor two-positive and triple
      negative cancers than for estrogen receptor-positive / progesterone receptor
      positive tumors (R1 P < 0.001-0.002; R2 P = 0.0.001-0.011). IER had higher
      sensitivity (80.6% vs. 75.5%) and specificity (55.8% vs. 48.1%) than washout
      curves for positive nodes, higher specificity (48.1% vs. 36.5%) and positive
      predictive value (70.2% vs. 66.7%) for high ki-67, and excellent interobserver
      agreement (intraclass correlation coefficient = 0.82). DATA CONCLUSION: IER, a
      measurement of early contrast washin, is associated with higher-grade
      malignancies and tumor aggressiveness and might be potentially incorporated into
      an AB-MRI protocol. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn.
      Reson. Imaging 2018;47:1692-1700.

PMID- 29178259
TI  - The Effect of Different l-Carnitine Administration Routes on the Development of
      Atherosclerosis in ApoE Knockout Mice.
AB  - SCOPE: l-Carnitine (LC) is abundant in red meat and is widely added to health
      supplements and food. This study focuses on the adverse effects of oral
      supplementation of 1.3% LC in ApoE-/- mice and whether the parenteral
      administration of LC (subcutaneously, sub) has any impact on the development of
      atherosclerosis. METHODS AND RESULTS: Mice are randomly divided into three groups
      (n = 15). All mice are fed a high-fat diet (HFD). The number of Ly6Chi monocytes;
      degree of atherosclerosis; plasma LC, gamma-butyrobetaine (gammaBB), and
      trimethylamine-N-oxide (TMAO) levels; and microbial community composition are
      analyzed. Compared with the HFD and HFD +/- LC (sub) groups, the number of Ly6Chi
      monocytes, atherosclerotic plaque area, and plasma gammaBB and TMAO levels are
      increased in the HFD +/- LC (oral) group (p < 0.001). Plasma LC levels in the HFD
      +/- LC (sub) group are higher than those in other groups. The levels of gammaBB,
      TMAO, and Ly6Chi monocytes are positively correlated with atherosclerotic plaque
      area (p < 0.01), and TMAO is positively correlated with Bacteroidetes and
      negatively correlated with Firmicutes at the phylum level. CONCLUSION: In
      contrast with oral LC administration, subcutaneous LC administration, which
      bypasses its conversion to TMAO in the liver, does not have a detrimental effect
      on the development of atherosclerosis in male ApoE-/- mice. Taking LC
      parenterally may be preferable among patients who require LC supplementation.

PMID- 29178260
TI  - Origin of clear cell carcinoma: nature or nurture?
AB  - A rare but serious complication of endometriosis is the development of carcinoma,
      and clear cell and endometrioid carcinomas of the ovary are the two most common
      malignancies which arise from endometriosis. They are distinct diseases,
      characterized by unique morphologies, immunohistochemical profiles, and responses
      to treatment. However, both arise in endometriosis and can share common
      mutations. The overlapping mutational profiles of clear cell and endometrioid
      carcinomas suggest that their varied histologies may be due to a different cell
      of origin which gives rise to each type of cancer. Cochrane and colleagues
      address this question in a recent article in this journal. They show that a
      marker of ovarian clear cell carcinoma, cystathionine gamma lyase, is expressed
      in ciliated cells. Similarly, they show that markers of secretory cells (estrogen
      receptor and methylenetetrahydrofolate dehydrogenase 1) are expressed in ovarian
      endometrioid carcinoma. Taken together, they suggest that endometrioid and clear
      cell carcinomas arise from cells related to secretory and ciliated cells,
      respectively. We discuss Cochrane et al's work in the context of other efforts to
      determine the cell of origin of gynecological malignancies, with an emphasis on
      recent developments and challenges unique to the area. These limitations
      complicate our interpretation of tumor differentiation; does it reflect nature
      imposed by a specific cell of origin or nurture, by either mutation(s) or
      environment? Copyright (c) 2017 Pathological Society of Great Britain and
      Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29178262
TI  - Selective detection of alpha4beta1 integrin (VLA-4)-expressing cells using
      peptide-functionalized nanostructured materials mimicking endothelial surfaces
      adjacent to inflammatory sites.
AB  - Persistent accumulation of immune cells mediated by alpha4beta1 integrin (VLA-4)
      is a hallmark of the inflammatory diseases and of chronic inflammation observed
      in the affected tissues of autoimmune diseases. Aiming at exploring new methods
      for monitoring the course of the inflammatory processes, we designed the first
      peptide-functionalized nanostructured devices capable to mimic the high-density
      multivalency binding between the alpha4beta1 integrin-expressing cells and the
      ligands overexpressed on the endothelial surfaces, in the proximity of the sites
      of inflammation. Specifically, we describe the first examples of monolayers
      constituted by dye-loaded zeolite L crystals, coated with alpha4beta1 integrin
      peptide ligands, and we analyze the adhesion of model Jurkat cells in comparison
      to non-alpha4beta1 integrin-expressing cells. In particular, the peptidomimetic
      diphenylurea-Leu-Asp-Val-diamine allows significant and selective detection of
      alpha4beta1 integrin-expressing Jurkat cells, after very rapid incubation time,
      supporting the possible implementation in a diagnostic device capable to detect
      the desired cells from biological fluids, obtainable from patients in a
      noninvasive way.

PMID- 29178261
TI  - An ANMS-NASPGHAN consensus document on esophageal and antroduodenal manometry in
      children.
AB  - BACKGROUND: Upper gastrointestinal symptoms in children are common and motility
      disorders are considered in the differential diagnosis. High resolution
      esophageal manometry (HRM) has revolutionized the study of esophageal physiology,
      and the addition of impedance has provided new insights into esophageal function.
      Antroduodenal motility has provided insight into gastric and small bowel
      function. PURPOSE: This review highlights some of the recent advances in
      pediatric esophageal and antroduodenal motility testing including indications,
      preparation, performance, and interpretation of the tests. This update is the
      second part of a two part series on manometry studies in children (first part was
      on anorectal and colonic manometry [Neurogastroenterol Motil. 2016;29:e12944]),
      and has been endorsed by the North American Society for Pediatric
      Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the American
      Neurogastroenterology and Motility Society (ANMS).

PMID- 29178263
TI  - Characterizing the free volume of ultrahigh molecular weight polyethylene to
      predict diffusion coefficients in orthopedic liners.
AB  - Liners used in orthopedic devices are often made from ultrahigh molecular weight
      polyethylene (UHMWPE). A general predictive capability for transport coefficients
      of small molecules in UHMWPE does not exist, making it difficult to assess
      properties associated with leaching or uptake of small molecules. To address this
      gap, we describe here how a form of the Vrentas-Duda free volume model can be
      used to predict upper-bound diffusion coefficients (D) of arbitrary molecules
      within UHMWPE on the basis of their size and shape. Within this framework, the
      free-volume microstructure of UHMWPE is defined by analysis of a curated set of
      model diffusants. We determined an upper limit on D for vitamin E, a common
      antioxidant added to UHMWPE, to be 7.1 * 10-12 cm2  s-1 . This means that a liner
      that contains 0.1 wt % or less Vitamin E and has <120 cm2 patient contacting
      surface area would elute <100 ug/day of vitamin E. Additionally, the model
      predicts that squalene and cholesterol-two pro-oxidizing biological compounds-do
      not penetrate over 820 um into UHMWPE liners over the course of 5 years because
      their D is <=7.1 * 10-12 cm2  s-1 . (c) 2017 Wiley Periodicals, Inc. J Biomed
      Mater Res Part B: Appl Biomater, 106B: 2393-2402, 2018.

PMID- 29178264
TI  - Assessing the validity of self-reported history of rash caused by metal or
      jewellery.
AB  - BACKGROUND: The use of metal-containing bio-devices is becoming increasingly
      common. Self-reported history of dermatitis with metal exposure is not
      established as being predictive for metal allergy. OBJECTIVES: To assess the
      validity of two screening questions addressing metal allergy. METHODS: At
      Massachusetts General Hospital Contact Dermatitis Clinic, 2132 consecutive
      patients were asked either 'Do you get rashes when jewellery touches your skin'
      (Q1; N = 1816) or 'Do you get rashes when metal touches your skin?' (Q2; N = 316)
      before being patch tested. RESULTS: Testing showed that 20% of subjects had
      positive reactions to nickel, 7.4% had positive reactions to cobalt, and 5.8% had
      positive reactions to chromium. Q1 was 40% sensitive (95%CI: 35-45%). The
      positive predictive value (PPV) was 51%, and the negative predictive value (NPV)
      was 82%. Q2 was 77% sensitive (95%CI: 68-84%). The PPV was 71%, and the NPV was
      84%. Q2 was 37% more sensitive than Q1 (p < 0.0001), with a higher relative risk
      (RR) (4.75, p < 0.001) than Q1 (RR = 3.01, p < 0.001). CONCLUSIONS: Patient
      reported metal allergy, although not perfect, is a reasonable method for metal
      allergy screening to help identify those needing further objective evaluation by
      patch testing.

PMID- 29178265
TI  - Surgical interventions for vertical strabismus in superior oblique palsy.
AB  - BACKGROUND: Superior oblique palsy is a common cause of vertical strabismus in
      adults and children. Patients may be symptomatic from binocular vertical diplopia
      or compensatory head tilt required to maintain single vision. Most patients who
      are symptomatic elect to undergo strabismus surgery, but the optimal surgical
      treatment for vertical strabismus in people with superior oblique palsy is
      unknown. OBJECTIVES: To assess the relative effects of surgical treatments
      compared with another surgical intervention, non-surgical intervention, or
      observation for vertical strabismus in people with superior oblique palsy. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
      (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12),
      MEDLINE Ovid (1946 to 13 December 2016), Embase Ovid (1947 to 13 December 2016),
      Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982
      to 13 December 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch);
      searched 13 December 2016, ClinicalTrials.gov (www.clinicaltrials.gov); searched
      13 December 2016, and the World Health Organization (WHO) International Clinical
      Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 13
      December 2016. We did not use any date or language restrictions in the electronic
      searches for trials. SELECTION CRITERIA: We included randomized trials that
      compared at least one type of surgical intervention to another surgical or non
      surgical intervention or observation. DATA COLLECTION AND ANALYSIS: Two review
      authors independently completed eligibility screening, data abstraction, 'Risk of
      bias' assessment, and grading of the evidence. MAIN RESULTS: We identified two
      randomized trials comparing four different surgical treatments for this
      condition, two methods in each trial. The studies included a total of 45 children
      and adults. The surgical treatments were all procedures to weaken the ipsilateral
      inferior oblique muscle. One study compared inferior oblique myectomy to
      recession of 10 mm; the other study compared inferior oblique disinsertion to
      anterior transposition (2 mm anterior to the temporal border of the inferior
      rectus insertion).We judged both studies to be at unclear risk of bias due to
      incomplete reporting of methods and other methodological deficiencies.Neither
      study reported data on the primary outcome of this review, which was the
      proportion of participants with postoperative surgical success, defined as
      hypertropia less than 3 prism diopters (PD) in primary gaze. However, both
      studies reported the average reduction in hypertropia in primary gaze. One study
      found that at 12 months' postoperatively the average decrease in hypertropia was
      higher in participants who underwent inferior oblique myectomy than in those who
      underwent recession, however data were not available for statistical comparison.
      The other trial found that after at least six months of follow-up, the mean
      decrease in primary position hypertropia was lower in participants who underwent
      inferior oblique disinsertion than in those who underwent anterior transposition
      (mean difference (MD) -5.20 PD, 95% confidence interval (CI) -7.76 to -2.64;
      moderate-quality evidence).Both trials also reported the average postoperative
      reduction in vertical deviation in adduction. One study reported that the average
      reduction in hypertropia in adduction was greater in participants who underwent
      inferior oblique myectomy than in those who underwent recession, but data were
      not available for statistical comparison. The other study found a lower decrease
      in hypertropia in contralateral gaze in participants who underwent inferior
      oblique disinsertion than in those who underwent anterior transposition (MD -7.10
      PD, 95% CI -13.85 to -0.35; moderate-quality evidence).Secondary outcomes with
      sufficient data for analysis included proportion of participants with
      preoperative head tilt that resolved postoperatively and proportion of
      participants who underwent a second surgery. These outcomes were assessed in the
      trial comparing inferior oblique anterior transposition to disinsertion; both
      outcomes favored anterior transposition (risk ratio 7.00, 95% CI 0.40 to 121.39
      for both outcomes; very low-quality evidence). None of the participants who
      underwent inferior oblique anterior transposition or disinsertion developed
      postoperative hypotropia or reversal of the vertical deviation. All participants
      who underwent inferior oblique anterior transposition developed elevation
      deficiency, which the authors deemed to be clinically insignificant in all cases,
      whereas no participants who underwent inferior oblique disinsertion experienced
      this complication. Additionally, the trial comparing inferior oblique myectomy to
      recession reported that no participant in either group required another
      strabismus surgery during the postoperative period. AUTHORS' CONCLUSIONS: The two
      trials included in this review evaluated four inferior oblique weakening
      procedures for surgical treatment of superior oblique palsy. We found no trials
      comparing other types of surgical procedures for this disorder. Both studies had
      enrolled a small number of participants and provided low-quality evidence due to
      limitations in completeness and applicability. We therefore found no high-quality
      evidence to support recommendations for optimal surgical treatment of superior
      oblique palsy. Rigorously designed, conducted, and reported randomized trials are
      needed to identify the optimal surgical treatment for vertical strabismus in this
      disorder.

PMID- 29178266
TI  - Neurocognitive outcome in young adults born late-preterm.
AB  - AIM: This study examined whether late-preterm birth (34+0 to 36+6wks+d
      gestational age) was associated with neurocognitive deficit in young adulthood,
      and whether small for gestational age (SGA) birth amplified any adversity.
      METHOD: Participants derived from the prospective regional cohort study, the Arvo
      Ylppo Longitudinal Study (n=786; 398 females, 388 males) (mean age 25y 4mo, SD
      8mo), born 1985 to 1986 late-preterm (n=119; 21 SGA, <-2 SD) and at term (37+0 to
      41+6wks+d; n=667; 28 SGA) underwent tests of intelligence, executive functioning,
      attention, and memory, and reported their education. RESULTS: Those born late
      preterm scored -3.71 (95% confidence interval [CI] -6.71 to -0.72) and -3.11 (95%
      CI -6.01 to -0.22) points lower on Full-scale and Verbal IQ than peers born at
      term. Compared with those born at term and appropriate for gestational age (>=-2
      to <2 SD) Full-scale, Verbal, and Performance IQ scores of those born late
      preterm and SGA were -9.45 to -11.84 points lower. After adjustments, differences
      were rendered non-significant, except that scores in Full-scale and Performance
      IQ remained lower among those born late-preterm and SGA. INTERPRETATION: Late
      preterm birth, per se, may not increase the risk of poorer neurocognitive
      functioning in adulthood. But the double burden of being born late-preterm and
      SGA seems to increase this risk. WHAT THIS PAPER ADDS: Late-preterm birth did not
      increase the risk of poorer neurocognitive functioning in adulthood. But the
      double burden of being born late-preterm and being small for gestational age did
      increase this risk.

PMID- 29178267
TI  - Tracing the origins of genotype VIIh Newcastle disease in southern Africa.
AB  - It is widely accepted that Newcastle disease is endemic in most African
      countries, but little attention has been afforded to establishing the sources and
      frequency of the introductions of exotic strains. Newcastle disease outbreaks
      have a high cost in Africa, particularly on rural livelihoods. Genotype VIIh
      emerged in South-East Asia and has since caused serious outbreaks in poultry in
      Malaysia, Indonesia, southern China, Vietnam and Cambodia. Genotype VIIh reached
      the African continent in 2011, with the first outbreaks reported in Mozambique.
      Here, we used a combination of phylogenetic evidence, molecular dating and
      epidemiological reports to trace the origins and spread of subgenotype VIIh
      Newcastle disease in southern Africa. We determined that the infection spread
      northwards through Mozambique, and then into the poultry of the north-eastern
      provinces of Zimbabwe. From Mozambique, it also reached neighbouring Malawi and
      Zambia. In Zimbabwe, the disease spread southward towards South Africa and
      Botswana, causing outbreaks in backyard chickens in early-to-mid 2013. In August
      2013, the disease entered South Africa's large commercial industry, and the
      entire country was infected within a year, likely through fomites and the
      movements of cull chickens. Illegal poultry trading or infected waste from ships
      and not wild migratory birds was the likely source of the introduction to
      Mozambique in 2011.

PMID- 29178268
TI  - Selective extraction of morphine from biological fluids by magnetic molecularly
      imprinted polymers and determination using UHPLC with diode array detection.
AB  - The determination of morphine concentration in the blood and urine is necessary
      for patients and recruitment purposes. Herein, a magnetic molecularly imprinted
      polymer for selective and efficient extraction of morphine from biological
      samples was synthesized by using a core-shell method. Fe3 O4 nanoparticles were
      coated with SiO2 -NH2 . The molecularly imprinted polymer was coated on the Fe3
      O4 /SiO2 -NH2 surface by the copolymerization of methacrylic acid and ethylene
      glycol dimethacrylate in the presence of morphine as the template molecule. The
      morphological and magnetic properties of the polymer were investigated. Field
      emission scanning electron microscopy indicated that the prepared magnetic
      polymer is almost uniform. The saturation magnetization values of Fe3 O4
      nanoparticles, Fe3 O4 /SiO2 -NH2 , and the magnetic polymer were 48.41, 31.69,
      and 13.02 emu/g, respectively, indicating that all the particles are
      superparamagnetic. Kinetics of the adsorption of morphine on magnetic polymer
      were well described by second-order kinetic and adsorption processes and well
      fitted by the Langmuir adsorption isotherm, in which the maximum adsorption
      capacity was calculated as 28.40 mg/g. The recoveries from plasma and urine
      samples were in the range of 84.9-105.5 and 94.9-102.8%, respectively. By using
      the magnetic molecularly imprinted polymer, morphine can selectively, reliably,
      and in low concentration be determined in biological samples with high
      performance liquid chromatography and UV detection.

PMID- 29178269
TI  - Unmodern Synthesis: Developmental Hierarchies and the Origin of Phenotypes.
AB  - The question of whether the modern evolutionary synthesis requires an extension
      has recently become a topic of discussion, and a source of controversy. We
      suggest that this debate is, for the most part, not about the modern synthesis at
      all. Rather, it is about the extent to which genetic mechanisms can be regarded
      as the primary determinants of phenotypic characters. The modern synthesis has
      been associated with the idea that phenotypes are the result of gene products,
      while supporters of the extended synthesis have suggested that environmental
      factors, along with processes such as epigenetic inheritance, and niche
      construction play an important role in character formation. We argue that the
      methodology of the modern evolutionary synthesis has been enormously successful,
      but does not provide an accurate characterization of the origin of phenotypes.
      For its part, the extended synthesis has yet to be transformed into a testable
      theory, and accordingly, has yielded few results. We conclude by suggesting that
      the origin of phenotypes can only be understood by integrating findings from all
      levels of the organismal hierarchy. In most cases, parts and processes from a
      single level fail to accurately explain the presence of a given phenotypic trait.

PMID- 29178270
TI  - Asymmetric Synthesis of 2H-Azirines with a Tetrasubstituted Stereocenter by
      Enantioselective Ring Contraction of Isoxazoles.
AB  - Highly strained 2H-azirines with a tetrasubstituted stereocenter were synthesized
      by the enantioselective isomerization of isoxazoles with a chiral diene-rhodium
      catalyst system. The effect of ligands and the coordination behavior support the
      proposed catalytic cycle in which the coordination site is fixed in favor of
      efficient enantiodiscrimination by a bulky substituent of the ligand. In silico
      studies also support the existence of a rhodium-imido complex as a key
      intermediate for enantiodiscrimination.

PMID- 29178271
TI  - Assessment of the relationship between the maxillary sinus floor and the upper
      posterior root tips: Clinical considerations.
AB  - AIM: The purpose of the present study was to evaluate the relationship between
      the maxillary sinus floor and the upper posterior root tips in the Colombian
      population using cone-beam computed tomography. METHODS: A total of 1656 roots
      were analyzed (1104 molars and 552 premolars), classified as types I (outside the
      maxillary sinus) and II (inside the maxillary sinus). RESULTS: The results showed
      that the palatal root of the maxillary first molar was most frequently found
      inside the antrum. CONCLUSIONS: Understanding the relationship between the
      maxillary sinus floor and the upper posterior root tips is important to the
      clinician when performing conventional or surgical endodontic treatment and
      conventional surgery procedures in order to minimize or avoid the risk of
      damaging the maxillary sinus.

PMID- 29178272
TI  - Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions
      using a model informed cocktail reaction phenotyping trial protocol.
AB  - AIM: To evaluate the capacity for modafinil to be a perpetrator of metabolic drug
      drug interactions by altering cytochrome P450 activity following a single dose
      and dosing to steady state. METHODS: A single centre, open label, single sequence
      cocktail drug interaction trial. On days 0, 2 and 8 participants were
      administered an oral drug cocktail comprising 100 mg caffeine, 30 mg
      dextromethorphan, 25 mg losartan, 1 mg midazolam and 20 mg enteric-coated
      omeprazole. Timed blood samples were collected prior to and for up to 6 h post
      cocktail dosing. Between days 2 and 8 participants orally self-administered 200
      mg modafinil each morning. RESULTS: Following a single 200 mg dose of modafinil
      mean (+/- 95% CI) AUC ratios for caffeine, dextromethorphan, losartan, midazolam
      and omeprazole were 0.95 (+/- 0.08), 1.01 (+/- 0.35), 0.97 (+/- 0.10), 0.98 (+/-
      0.10) and 1.36 (+/- 0.06), respectively. Following dosing of modafinil to steady
      state (200 mg for 7 days), AUC ratios for caffeine, dextromethorphan, losartan,
      midazolam and omeprazole were 0.90 (+/- 0.16), 0.79 (+/- 0.09), 0.98 (+/- 0.11),
      0.66 (+/- 0.12) and 1.90 (+/- 0.53), respectively. CONCLUSIONS: These data
      support consideration of the risk of clinically relevant metabolic drug-drug
      interactions perpetrated by modafinil when this drug is co-administered with
      drugs that are primarily cleared by CYP2C19 (single modafinil dose or steady
      state modafinil dosing) or CYP3A4 (steady state modafinil dosing only) catalysed
      metabolic pathways.

PMID- 29178273
TI  - Port Placement for Laparoscopic Colonic Resections - Video Vignette.
AB  - Laparoscopic colonic resections often require manipulation and surgical action in
      all abdominal quadrants. Port placement, a fundamental part of a successful
      procedure, often varies widely among surgeons and is currently dictated by
      individual experience and preference. This variability may be suboptimal for the
      operation at hand, can be confusing for trainees and many times provide
      inadequate working posture for the surgeons, resulting in discomfort due to
      muscular fatigue in the hands, arms, shoulders and cervical spine. This article
      is protected by copyright. All rights reserved.

PMID- 29178275
TI  - Importance of uniform data collection and reporting in research: A call for a
      minimum dataset in sepsis.

PMID- 29178274
TI  - Lactate >=2 mmol/L plus qSOFA improves utility over qSOFA alone in emergency
      department patients presenting with suspected sepsis.
AB  - OBJECTIVE: The Sepsis-3 task force recommends the use of the quick Sequential
      Organ Failure Assessment (qSOFA) score to identify risk for adverse outcomes in
      patients presenting with suspected infection. Lactate has been shown to predict
      adverse outcomes in patients with suspected infection. The aim of the study is to
      investigate the utility of a post hoc lactate threshold (>=2 mmol/L) added qSOFA
      score (LqSOFA(2) score) to predict primary composite adverse outcomes (mortality
      and/or ICU stay >=72 h) in patients presenting to ED with suspected sepsis.
      METHODS: Retrospective cohort study was conducted on a merged dataset of
      suspected or proven sepsis patients presenting to ED across multiple sites in
      Australia and The Netherlands. Patients are identified as candidates for quality
      improvement initiatives or research studies at respective sites based on local
      screening procedures. Data-sharing was performed across sites of demographics,
      qSOFA, SOFA, lactate thresholds and outcome data for included patients. LqSOFA(2)
      scores were calculated by adding an extra point to qSOFA score in patients who
      met lactate thresholds of >=2 mmol/L. RESULTS: In a merged dataset of 12 555
      patients where a full qSOFA score and outcome data were available, LqSOFA(2) >=2
      identified more patients with an adverse outcome (sensitivity 65.5%, 95%
      confidence interval 62.6-68.4) than qSOFA >=2 (sensitivity 47.6%, 95% confidence
      interval 44.6- 50.6). The post hoc addition of lactate threshold identified
      higher proportion of patients at risk of adverse outcomes. CONCLUSIONS: The
      lactate >=2 mmol/L threshold-based LqSOFA(2) score performs better than qSOFA
      alone in identifying risk of adverse outcomes in ED patients with suspected
      sepsis.

PMID- 29178276
TI  - In this December issue.

PMID- 29178277
TI  - Traumatic dislocation of the first rib: A case report and review of the
      literature.

PMID- 29178279
TI  - Multimodality imaging of a pulmonary artery sarcoma.
AB  - Pulmonary artery sarcoma is a rare malignant neoplasm. Here, we describe a
      patient with a pulmonary artery sarcoma, which was only subtly visible and
      therefore not fully appreciated on initial transthoracic echocardiogram.
      Characterization of the tumor was aided by the use of multimodality imaging that
      included computed tomography, magnetic resonance imaging, and positron emission
      tomography. Familiarity with its appearance on multiple imaging modalities
      including echocardiography is important to ensure timely diagnosis, although the
      optimal treatment strategy is still unknown, and the prognosis remains poor.

PMID- 29178280
TI  - Warm-Up Effect in Panelist-Articulated-2-Alternative Forced Choice Test.
AB  - : Panelist performance in discrimination tests has been shown to increase when
      warm-up samples are provided prior to the actual test. Samples are used prior to
      the actual test for the attribute articulation process of a panelist-articulated
      2-alternative forced choice (PA-2-AFC) procedure; however, it is yet unknown if
      the pretest articulation phase adds to the power of this testing method as with
      the warm-up. The goal of the study was to determine if a "warm-up" effect was
      displayed in the PA-2-AFC test resulting in greater power compared to the
      researcher-designated-2-AFC (RD-2-AFC) test. A RD-2-AFC test, with and without
      warm-up samples, and a PA-2-AFC test were performed by 61 panelists. A reduced
      calorie, citrus-flavored, and carbonated beverage was used in the tests. During
      RD-2-AFC testing, panelists were asked to identify which sample was more sour.
      For PA-2-AFC testing, panelists individually articulated the nature and direction
      of the difference between the 2 samples through a pretesting articulation
      procedure. The articulated difference was, then, used in standard 2-AFC test
      procedure. A warm-up effect was observed when comparing the standard RD-2-AFC
      with and without warm-up samples. The addition of warm up samples significantly
      increased the power of the test, in addition, the PA-2-AFC method had lower power
      than the RD-2-AFC method. The increase in power with the addition of warm-up
      samples for the RD-2-AFC procedure supports literature findings on the benefit of
      providing warm-up samples. No warm-up effect can be attributed to the PA-2-AFC
      method evidenced by the overall low power observed, which may be attributed to
      sample complexity. PRACTICAL APPLICATION: Selecting a specified discrimination
      testing method is advantageous and can reduce costs of sensory testing, but has
      been considered unpractical when samples may differ in unknown ways. This
      research explores the use of panelist derived terms to circumvent the need for
      researchers to identify these differences and compares the results to using
      research designated terms in discrimination testing. Results from this study can
      be utilized in creating ways to incorporate more powerful methods into sensory
      discrimination testing plans and provides researchers with a means for selecting
      terms for use in specified discrimination testing methods.

PMID- 29178281
TI  - Abdominal girth and dorso-sacral distance can be used to estimate lumbosacral
      cerebral fluid volume.
AB  - BACKGROUND: Patients' abdominal girth and vertebral column length are highly
      correlated with the spread of local anaesthetics after spinal anaesthesia.
      Lumbosacral cerebrospinal fluid volume is the primary determinant for spinal
      spread. Thus, we attempted to verify the hypothesis that abdominal girth and
      dorso-sacral distance are correlated with lumbosacral cerebrospinal fluid volume.
      METHODS: Forty-five healthy volunteers were enrolled in this study to measure
      lumbosacral cerebrospinal fluid volume using magnetic resonance imaging. The age,
      height, weight, abdominal girth, dorso-sacral distance and lumbosacral
      cerebrospinal fluid volume of the volunteers were recorded. Multiple linear
      regression analysis was used to analyse the correlation between age, height,
      weight, abdominal girth, dorso-sacral distance and lumbosacral cerebrospinal
      fluid volume. RESULTS: Two volunteers were excluded because of lumbar disc
      herniation, leaving 43 volunteers for analysis. Multiple linear regression
      analysis showed a strong correlation between abdominal girth, dorso-sacral
      distance and lumbosacral cerebrospinal fluid volume (both P < 0.01). The adjusted
      R2 was 0.644. Volunteers with small abdominal girth showed clear images of
      cerebrospinal fluid in the nerve root cuff at the intervertebral foramen in the
      three-dimensional magnetic resonance imaging reconstruction of lumbosacral
      cerebrospinal fluid, while the images were vague in volunteers with large
      abdominal girth. Clearer images implied larger lumbosacral cerebrospinal fluid
      volume, while vaguer images, smaller lumbosacral cerebrospinal fluid volume.
      CONCLUSIONS: Multiple regression analysis revealed that abdominal girth and dorso
      sacral distance were correlated with lumbosacral cerebrospinal fluid volume.
      Smaller abdominal girths and larger dorso-sacral distances predict larger
      lumbosacral cerebrospinal fluid volume.

PMID- 29178282
TI  - Adolescent Perceptions of Parental Privacy Invasion and Adolescent Secrecy: An
      Illustration of Simpson's Paradox.
AB  - Adolescents' secrecy is intertwined with perception of parents' behaviors as acts
      of privacy invasion. It is currently untested, however, how this transactional
      process operates at the within-person level-where these causal processes take
      place. Dutch adolescents (n = 244, Mage  = 13.84, 38.50% boys) reported three
      times on perceived parental privacy invasion and secrecy. Cross-lagged panel
      models (CLPM) confirmed earlier findings. Privacy invasion predicted increased
      secrecy, but a reverse effect was found from increased secrecy to increased
      privacy invasion. Controlling for confounding positive group-level associations
      with a novel random intercept CLPM, negative within-person associations were
      found. Higher levels of secrecy predicted lower levels of privacy invasive
      behaviors at the within-person level. These opposing findings within- versus
      between-persons illustrate a Simpson's paradox.

PMID- 29178283
TI  - Insights into the epidemic characteristics and evolutionary history of the novel
      porcine circovirus type 3 in southern China.
AB  - Porcine circovirus type 3 (PCV3) is a newly identified circovirus from swine in
      the USA, China and Poland. This novel circovirus has been associated with porcine
      dermatitis and nephropathy syndrome (PDNS), reproductive failure and
      multisystemic inflammation; moreover, PCV3 poses a potential threat to the swine
      industry. In this retrospective study, a phylogenetic analysis was conducted to
      address the epidemiology and evolutionary dynamics of this novel circovirus. The
      total positive sample rate of PCV3 was 26.7% (76/285) and has increased gradually
      over the past 3 years. Of these PCV3-positive samples, 22.3% (17/76) were
      coinfected with PCV2. PCV3 can be detected in multiple sample types with
      different positive rates, and the positive rate is highest among stillborn. We
      also divide PCV3 into three clades (PCV3a, PCV3b and PCV3c) based on two amino
      acid mutations (A24V and R27K) on the cap protein in this study. In addition, the
      origin of PCV3 was approximately 1966 and may have originated from a bat
      associated circovirus. Our results suggested that PCV3 is widely distributed in
      southern China and has been circulating in swine herds for nearly half a century.
      PCV3 has evolved into different clades caused by mutations in cap proteins; thus,
      further research on PCV3 epidemiology should be conducted.

PMID- 29178284
TI  - Nitric oxide inhalations in bronchiolitis: A pilot, randomized, double-blinded,
      controlled trial.
AB  - AIM: The aims of this pilot study were to determine safety, tolerability (primary
      outcome) and efficacy (secondary outcome) of high-dose inhaled nitric oxide for
      the treatment of infants with moderately severe bronchiolitis. METHODS: This was
      a pilot, double-blinded, randomized controlled study (phase IIa). Intermittent
      inhalations of nitric oxide 160 ppm for 30 min or oxygen/air (control) were given
      5 times/day to hospitalized infants (2-11 months) with acute bronchiolitis.
      Oxygen saturation, methemoglobin, and nitric dioxide (NO2 ) levels and vital
      signs were monitored. RESULTS: Forty-three infants were enrolled. Baseline
      characteristics were comparable in both study groups. Mean clinical score,
      comprised of four components: respiratory rate, use of accessory muscles, wheezes
      and crackles, and % room-air oxygen saturation, was 7.86 (+/-1.1) and 8.09 (+/
      1.2) in the NO and control groups, respectively, consistent with moderate
      severity. The overall frequency of adverse events was similar between the groups.
      Repeated nitric oxide inhalations did not result in increased inhaled NO2 levels
      or cumulative effect on methemoglobin levels. Secondary outcomes of efficacy were
      measured by length of hospitalization (LOS) in hours: LOS did not differ between
      groups. However, in a post-hoc analysis of a subgroup of infants hospitalized for
      >24 h (n = 24), the median LOS was shorter in the nitric oxide (41.9 h) than in
      the control group (62.5 h) (P = 0.014). CONCLUSION: Our study was unable to
      detect a difference in side effects using intermittent high-dose nitric-oxide
      inhalation or supportive treatment alone, in infants with moderate bronchiolitis.
      Preliminary efficacy outcomes are encouraging.

PMID- 29178286
TI  - Contrasting responses of crop legumes and cereals to nitrogen availability.
AB  - In nonagricultural systems, the relationship between intrinsic water-use
      efficiency (WUEi ) and leaf nitrogen (Narea ) is known to be stronger for legumes
      than for nonlegumes. We tested whether these relationships are retained for major
      agricultural legumes and nonlegumes. We compared the response to N nutrition of
      WUEi (and its component parts, photosynthesis (Asat ) and stomatal conductance
      (gs )) for legumes Cicer arietinum, Glycine max, Lupinus alba and Vicia faba,
      nonlegume dicots Brassica napus and Helianthus annus, and nonlegume cereals
      Hordeum vulgare and Triticum aestivum. Surprisingly, and in contrast to studied
      cereals and nonlegume dicots, Narea was positively related to photosynthesis in
      the legumes, explaining nearly half of the variance in Asat . WUEi was tightly
      coupled to Narea for agricultural legumes and nonlegume dicots, but not for
      cereal crops. Our analysis suggests that breeding efforts to reduce gs in legumes
      could increase WUEi by 120-218% while maintaining Asat at nonlegume values.
      Physiologically informed breeding of legumes can enhance sustainable agriculture
      by reducing requirements for water and N.

PMID- 29178285
TI  - Template-based quaternary structure prediction of proteins using enhanced profile
      profile alignments.
AB  - Proteins often exist as their multimeric forms when they function as so-called
      biological assemblies consisting of the specific number and arrangement of
      protein subunits. Consequently, elucidating biological assemblies is necessary to
      improve understanding of protein function. Template-Based Modeling (TBM), based
      on known protein structures, has been used widely for protein structure
      prediction. Actually, TBM has become an increasingly useful approach in recent
      years because of the increased amounts of information related to protein amino
      acid sequences and three-dimensional structures. An apparently similar situation
      exists for biological assembly structure prediction as protein complex structures
      in the PDB increase, although the inference of biological assemblies is not a
      trivial task. Many methods using TBM, including ours, have been developed for
      protein structure prediction. Using enhanced profile-profile alignments, we
      participated in the 12th Community Wide Experiment on the Critical Assessment of
      Techniques for Protein Structure Prediction (CASP12), as the FONT team (Group #
      480). Herein, we present experimental procedures and results of retrospective
      analyses using our approach for the Quaternary Structure Prediction category of
      CASP12. We performed profile-profile alignments of several types, based on FORTE,
      our profile-profile alignment algorithm, to identify suitable templates. Results
      show that these alignment results enable us to find templates in almost all
      possible cases. Moreover, we have come to understand the necessity of developing
      a model selection method that provides improved accuracy. Results also
      demonstrate that, to some extent, finding templates of protein complexes is
      useful even for MEDIUM and HARD assembly prediction.

PMID- 29178287
TI  - Is temporal association between popliteal-sciatic block and nerve injury
      sufficient evidence to assign etiology?

PMID- 29178288
TI  - White oral mucosal lesions among the Yemeni population and their relation to
      local oral habits.
AB  - AIMS: The aim of the present study was to assess the prevalence and risk factors
      of white oral mucosal lesions among Yemeni adults; in particular, those who chew
      khat and tobacco. METHODS: The present cross-sectional study included 1052 dental
      patients aged 15 years and older. A detailed oral examination was performed by a
      single examiner in accordance with standard international criteria. RESULTS:
      Overall, 25.2% of the study participants presented with one or more white
      lesions. The most prevalent lesions were khat-induced white lesion (8.8%),
      leukoedema (5.1%), and frictional keratosis (3.9%). Potentially malignant
      lesions, such as lichen planus, leukoplakia, and smokeless tobacco-induced
      lesions, were seen in 2.4%, 1.2%, and 1.7% of participants, respectively.
      Moreover, three cases of oral cancer were identified. The presence of white
      lesions was found to be significantly associated with advanced age (P = .004),
      male gender (P = .009), and khat/tobacco chewing habits (P < .001). CONCLUSIONS:
      The present study demonstrates a high prevalence of oral benign and potentially
      malignant white lesions. Further, it highlights the urgent need to develop and
      implement new government policies to regulate the sale of these products to
      reduce the prevalence of these lesions and the overall incidence of oral cancers
      in the Yemeni population.

PMID- 29178290
TI  - MicroRNA-21 Contributes to Reduced Microvascular Function in Binge Drinking Young
      Adults.
AB  - BACKGROUND: Binge drinking is associated with increased risk for cardiovascular
      (CV) disease. MicroRNA-21 (miR21) is up-regulated in the setting of excessive
      alcohol consumption and CV disease. Therefore, the goal of this study was to
      examine the vasodilatory responses to flow and acetylcholine (ACh) in the absence
      and presence of an anti-miR21 inhibitor in the microcirculation of young adult
      repeated binge drinkers (BDs). METHODS: Gluteal subcutaneous adipose tissue
      biopsies were obtained from young adults (18 to 30 years, n = 35 vessels from BDs
      and n = 28 vessels from abstainers). Resistance arteries (RAs) were isolated,
      incubated with anti-miR21 or a negative control (NC) to miR21 (12 hours; 50 nM),
      and lumen diameters measured with video microscopy. miR21 of adipose tissues was
      determined by quantitative polymerase chain reaction. RESULTS: Flow-induced
      dilation and ACh-induced dilation (AChID) were reduced in BDs as compared to
      abstainers. The miR21 inhibitor but not the NC abrogated these effects in BDs,
      but did not affect vasodilation in abstainers. Nitric oxide synthase inhibition
      with L-NAME reduced vasodilation in abstainers but not in BDs. In BDs,
      vasodilation was reduced by L-NAME in the presence of anti-miR21 but not the NC.
      Scavenging the reactive oxygen species, hydrogen peroxide with polyethylene
      glycol catalase reduced dilation in BDs but did not affect the restored dilation
      by the miR21 inhibitor. Maximum dilation to papaverine (endothelium independent)
      was similar between groups and unaffected by pharmacological inhibition. Finally,
      vascular endogenous miR21 was increased in BDs compared to abstainers.
      CONCLUSIONS: Endogenous miR21 is increased in RAs of young BDs, leading to
      reduced flow and AChID in the microcirculation.

PMID- 29178289
TI  - Simultaneous quantitative assessment of nine glycosides in tobacco by liquid
      chromatography-tandem mass spectrometry.
AB  - A simple and efficient method combining ultrasound-assisted extraction, the
      conditions of which were optimized by response surface methodology, with liquid
      chromatography and tandem mass spectrometry was established and validated for the
      absolute quantification of nine non-volatile neutral glycosides originating from
      tobacco (Nicotiana tobaccum L.) leaves, comprising three phenolic glycosides, one
      benzanoid glycoside, and five sesquiterpene glycosides within three isomers,
      originating from tobacco leaves. Factors of extraction time, sample quantity,
      extraction solvent, liquid chromatographic conditions, and electrospray
      ionization parameters were carefully investigated to ensure the selectivity and
      sensitivity of the method. All calibration curves showed excellent coefficients
      of determination ranging from 0.9940 to 0.9996, within the range of tested
      concentrations. The limits of detection and quantification were 2.33-25.9 and
      7.06-78.5 ng/mL, respectively. Satisfactory values of accuracy were between 80.1
      to 107.9% among different sample matrixes. The relative standard deviations of
      intra- and inter-day analysis were less than 13.7 and 13.0% respectively. The
      developed method was successfully applied in a pilot study to determine the
      amounts of the nine endogenous glycosides in real flue-cured tobacco samples
      obtained from different habitats in China.

PMID- 29178291
TI  - Polyhedral 30-Faceted BiVO4 Microcrystals Predominantly Enclosed by High-Index
      Planes Promoting Photocatalytic Water-Splitting Activity.
AB  - Unprecedented 30-faceted BiVO4 polyhedra predominantly surrounded by {132},
      {321}, and {121} high-index facets are fabricated through the engineering of high
      index surfaces by a trace amount of Au nanoparticles. The growth of high-index
      facets results in a 3-5 fold enhancement of O2 evolution from photocatalytic
      water splitting by the BiVO4 polyhedron, relative to its low-index counterparts.
      Theory calculations reveal that water dissociation is more energetically
      favorable on the high-index surfaces than on the low-index (010), (110), and
      (101) surfaces, which is accompanied by a notable reduction in the overpotential
      (0.77-1.14 V) for the oxygen evolution reaction. The apparent quantum efficiency
      of O2 generation without an external electron supply reaches 18.3% under 430 nm
      light irradiation, which is an order of magnitude higher than that of the
      catalysts reported hitherto.

PMID- 29178292
TI  - Incubation media affect the survival, pathway and time of embryo development in
      Neotropical annual fish Austrolebias nigrofasciatus (Rivulidae).
AB  - To analyse the survival, pathway and time of embryo development in the annual
      fish Austrolebias nigrofasciatus eggs were monitored in four liquid media and two
      damp media under experimental conditions for 130 days until their development was
      complete. Eggs kept in the same breeding water from oviposition remained in
      diapause I (DI) during all experiments. In constrast, up to the stage prior to
      entering diapause II (DII), the other media had no influence on development.
      Embryos at this stage (DII), however, show longer development time when treated
      in medium with water and powdered coconut shell so that about 80% of embryos
      remained in DII at 100 days. In contrast, all other treatments had a
      significantly lower proportion of embryos remaining in DII. When treated with
      Yamamoto's solution in humid media, embryos showed the fastest development. The
      first fully developed embryos (DIII) were seen at 27 days after oviposition. It
      took an average of 46-58 days for 50% of eggs in each treatment to reach DIII.
      Compared with other studies, survival in all incubation media was high at between
      70 and 98%. Taken together, it can be concluded that all incubation media were
      found to be viable for maintaining embryos. Altering developmental trajectories
      through the manipulation of diapauses in different media makes this species a
      potential model organism for laboratory studies.

PMID- 29178293
TI  - Acute right heart failure caused by tacrolimus after renal transplantation:
      Serial observation by speckle tracking and Doppler echocardiography.
AB  - Tacrolimus is an immunosuppressive agent well known to be capable of producing
      renal impairment. Acute renal failure with right heart failure caused by
      tacrolimus is rarely described. We report the findings of one such case in which
      tacrolimus caused acute renal failure with severe tricuspid regurgitation and
      right ventricular failure documented by echocardiography.

PMID- 29178294
TI  - Advanced cardiac imaging techniques assist in characterizing a cardiac mass and
      directing management.
AB  - Advanced imaging techniques, including contrast echocardiography and CMR,
      provided valuable characterization and evaluation of a boy with an unusual
      cardiac mass. Imaging features assisted with differentiation of benign from
      malignant etiology and excluding thrombus. Accurate imaging techniques saved our
      patient risks associated with unnecessary surgery or anticoagulation. The ability
      to accurately define size serially assisted in guiding expectant management. He
      died from a noncardiac cause at age 28, and autopsy demonstrated a hamartoma of
      mature cardiac myocytes.

PMID- 29178296
TI  - Cor triatriatum dexter associated with atrial septal defect: Management in a
      complex clinical case.
AB  - The coexistence of an atrial septal defect and a prominent eustachian valve is a
      rare congenital anomaly, rarely reported in literature. Differentiation between a
      giant eustachian valve and cor triatriatum dexter can be difficult. A case of a
      large atrial septal defect associated with cor triatriatum dexter diagnosed by
      echocardiography in an asymptomatic woman is reported. A watchful waiting
      strategy was adopted.

PMID- 29178297
TI  - Frontal plane hip joint loading according to pain severity in people with hip
      osteoarthritis.
AB  - The primary objective was to examine the hip adduction moment during walking in
      people with hip osteoarthritis (OA) according to pain severity. Sixty-eight
      participants with unilateral symptomatic hip OA were included. Pain during
      walking was assessed on a 5-point Likert item within the Western Ontario and
      McMaster Universities Index (no pain = 12; mild pain n = 37; moderate pain n =
      19). Measures of the external hip adduction moment (peaks, Nm/BW * BH (%) and
      impulse, Nm.s/BW * BH (%)) were determined. Other measures included frontal plane
      hip, pelvis and trunk kinematics, walking speed and peak isometric hip abductor
      strength. Variables were compared according to pain severity using linear models
      and biomechanical variables were examined. Participants with moderate pain had a
      significantly higher second peak hip adduction moment and impulse compared to
      those with less pain. There was no difference in any measure of hip adduction
      moment between those with mild pain and no pain. There were no differences in
      kinematics across pain severity categories. Participants with moderate pain had a
      significantly slower walking speed compared to participants with mild and no
      pain. Participants with moderate pain had weaker peak isometric hip abductor
      strength compared to those with mild pain and no pain. The hip adduction moment
      during walking, hip abduction strength and walking speed differs according to
      pain severity during walking in people with hip OA. (c) 2017 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1637-1644, 2018.

PMID- 29178298
TI  - Transcranial magnetic stimulation does not improve mild cognitive impairment in
      Parkinson's disease.

PMID- 29178299
TI  - Nitrite Reduction in Aqueous Solution Mediated by Amavadin Homologues: N2 O
      Formation and Water Oxidation.
AB  - Reactions of two vanadium(IV) complex anions that are homologues of amavadin,
      [V(HIDPA)2 ]2- and [V(HIDA)2 ]2- (HIDPA=N-oxyiminodipropionate, HIDA=N
      oxyiminodiacetate), with the nitrite ion (NO2- ) in aqueous solution were
      investigated by experimental (absorption spectroscopy in the visible range,
      through measurements of dioxygen formed in solution from water oxidation and
      identification of nitrogen oxide species of a gaseous atmosphere from nitrite
      reduction by using an IR analyser) and theoretical methods. Two reactions,
      mediated by the vanadium complexes, with environmental and biological
      significance, were observed in this system, namely, reduction of nitrite to N2 O
      and oxidation of water to molecular oxygen. The reduction of nitrite, as studied
      by DFT calculations, occurs through the formation of NO (DeltaG? =14.3 kcal mol-1
      ), which is strongly dependent on pH and slightly endergonic, and is then easily
      converted into N2 O, with an overall activation barrier of DeltaG? =11.8 kcal mol
      1 . The later process includes dimerisation of NO assisted by one molecule of the
      V complex, protonation and oxidation of the formed ONNO.- ligand by another
      amavadin molecule or by nitrite, and NO bond cleavage/proton transfer in the
      ONNOH- ligand. The results indicate that amavadin exhibits an unusual nitrite
      reductase type activity that could be involved in nitrogen metabolism of Amanita
      muscaria and other fungi containing this vanadium complex.

PMID- 29178300
TI  - "I'm Having a Little Struggle With This, Can You Help Me Out?": Examining Impacts
      and Processes of a Social Capital Intervention for First-Generation College
      Students.
AB  - Social capital plays a key role in college and career success, and research
      indicates that a dearth of on-campus connections contributes to challenges first
      generation college students face in effectively navigating the college
      environment. This study investigates a novel intervention that focuses on the
      development of skills and attitudes to empower first-generation college students
      to cultivate social capital and on-campus connections during the transition to
      college. A mixed methods, explanatory design was used to evaluate impacts and
      processes of the intervention among first-generation college students (n = 164)
      in the context of an ethnically diverse, urban, public university in the
      Northeast. Results indicated that students who participated in the intervention
      demonstrated improved attitudes and behaviors around seeking support in college,
      closer relationships with instructors, and higher GPAs at the end of their first
      year in college. These results suggest the potential benefits of a relatively
      scalable approach to supporting the needs of first-generation college students.

PMID- 29178301
TI  - Histiocytic necrotizing lymphadenitis (Kikuchi's disease) with vasculitis.

PMID- 29178302
TI  - Circular dichroism of surface complexes based on quantum dots and azo dye.
AB  - Chiral properties of surface complexes based on CdSe/ZnS quantum dots (QDs) and 1
      (2-pyridylazo)-2-naphthol (PAN) azo dye were investigated by circular dichroism
      spectroscopy. The use of L-, D-cysteine (Lcys, Dcys) capping ligands allowed us
      to obtain water-soluble chiral QD-PAN complexes. The characterization of the
      complexes was performed by UV-vis, FTIR, and CD spectroscopy. Quantum chemical
      TDDFT calculated CD spectra reproduced the experimentally observed sign patterns,
      which originate from binding Lcys or Dcys and PAN molecules to the same Zn atom
      on the QD surface. The resulting complex is characterized by a large circular
      dichroism in comparison with an ordinary QD chirality induced by cysteine
      molecules. The pattern of CD signal is the same for Lcys and Dcys ligands in
      chiral QD-PAN complex.

PMID- 29178303
TI  - AANEM Choosing Wisely - second list.
AB  - Choosing Wisely is an initiative of the ABIM Foundation in partnership with
      Consumer Reports that seeks to advance a national dialogue on avoiding wasteful
      or unnecessary medical tests, treatments and procedures. The American Association
      for Neuromuscular & Electrodiagnostic Medicine's (AANEM) Professional Practice
      Committee (PPC) identified areas in neuromuscular and electrodiagnostic medicine
      that have the greatest potential for overuse/misuse and provided five
      recommendations for both patients and physicians to consider before proceeding
      with the specified test or treatment. This is the second list created by the PPC.
      The first was published in 2015. A combined list can be found online:
      http://www.choosingwisely.org/societies/american-association-of-neuromuscular
      electrodiagnostic-medicine/. Muscle Nerve 57: 335-336, 2018.

PMID- 29178304
TI  - Application of pH-zone-refining countercurrent chromatography in the chiral
      separation of two beta-adrenergic blocking agents.
AB  - Two beta-adrenergic blocking agents, 1-[(1-methylethyl)amino]-3-phenoxy-2
      propanol (1) and 1-[(1-methylethyl)amino]-3-(3-methylphenoxy)-2-propanol (2;
      Toliprolol), were enantioseparated by pH-zone-refining countercurrent
      chromatography. A two-phase solvent system composed of chloroform containing 0.10
      mol/L of di-n-hexyl l-tartrate/0.10 mol/L of boric acid aqueous solution (1:1,
      v/v) was selected, in which 20 mmol/L triethylamine was added in the organic
      phase as a retainer and 2 mmol/L HCl was added in the aqueous phase as an eluter.
      Fifty milligrams of each racemate was completely enantioseparated by pH-zone
      refining countercurrent chromatography to yield each enantiomer with a purity of
      more than 98%, and the recovery of each separated enantiomer reached around 76
      82%.

PMID- 29178305
TI  - En Bloc Resection with the Assistance of Video-Assisted Thoracoscopy for Left
      Lower Lung Cancer Invading Thoracic Vertebrae and Rib: A Case Report.
AB  - Lung cancer invading the spine was previously considered unresectable and fatal
      and, consequently, there are few reports focusing on tumors located in the lower
      lung lobe and invading the spine. With the development of spinal instrumentation
      and surgical techniques, and wider acceptance of spondylectomy by surgeons,
      radical surgical resection has become feasible. Here, we present a case of a male
      patient with a left lower lung cancer invading thoracic vertebrae who underwent
      complete resection with sagittal en bloc hemivertebrectomy with video-assisted
      thoracoscopy. A 60-year-old man complained of left chest pain for 3 months. Chest
      computed tomography and thoracic vertebrae magnetic resonance image revealed that
      a tumor in the left lower lung lobe had invaded the seventh and eighth thoracic
      vertebrae and the eighth rib. As no lymph node or distant metastasis was detected
      by positron emission tomography-computed tomography, the patient was diagnosed
      with left lower lung cancer directly invading the seventh and eighth thoracic
      vertebrae and the eighth rib (T4N0M0, stage IIIA) instead of metastasizing to the
      thoracic vertebrae. An en bloc resection of the lung tumor and the involved
      vertebrae was performed by a thoracic surgeon and orthopaedic surgeon with video
      assisted thoracoscopy. Six months after the operation, there was no evidence of
      local recurrence, and the patient had recovered well. En Bloc resection with
      video-assisted thoracoscopy for lung cancer invading thoracic vertebrae is a safe
      and feasible surgical method. This method can significantly improve the safety
      and convenience of this type of surgery.

PMID- 29178306
TI  - Outcomes of Short Fusion versus Long Fusion for Adult Degenerative Scoliosis: A
      Systematic Review and Meta-analysis.
AB  - The objective of this study was to evaluate differences in clinical and
      radiographic outcomes between short (<3 levels) and long (>=3 levels) fusions in
      the setting of degenerative lumbar scoliosis. A literature search was performed
      from six electronic databases. The key terms of "degenerative scoliosis" OR
      "lumbar scoliosis" AND "fusion" were combined and used as MeSH subheadings. From
      relevant studies identified, demographic data, complication rates, Oswestry
      Disability Index (ODI), and radiographic parameters were extracted and the data
      was pooled and analyzed. Long fusion was associated with comparable overall
      complication rates to short fusion (17% vs 14%, P = 0.20). There was a
      significant difference in the incidence of pulmonary complications when comparing
      short versus long fusion (0.42% vs 2.70%; P = 0.02). No significant difference
      was found in terms of motor, sensory complications, infections, construct-related
      or cardiac complications, pseudoarthrosis, dural tears, cerebrospinal fluid (CSF)
      leak, or urinary retention. A longer fusion was associated with a greater
      reduction in coronal Cobb angle and increases in lumbar lordosis, but both
      findings failed to achieve statistical significance. The ODI was comparable
      across both cohorts. If shorter fusion lengths are clinically indicated, they
      should be used instead of longer fusion lengths to reduce perioperative time,
      costs, and some other complications. However, there are no statistically
      significant differences in terms of radiographically measurable restoration
      associated with a short or long fusion.

PMID- 29178307
TI  - Influence of Postoperative Hypertension on the Development of Spinal Epidural
      Hematoma.
AB  - Spinal epidural hematoma (SEH) is a rare postoperative complication but can
      result in catastrophic neurological deficits requiring immediate surgical
      evacuation of the hematoma. Knowing the risk factors for postoperative SEH can
      help surgeons stratify patients. Therefore, to identify possible risk factors for
      postoperative SEH, we reviewed 6 clinical cases and examined the relation between
      postoperative hypertension and the risk of developing SEH. A retrospective review
      was conducted of 1282 consecutive patients who underwent spinal surgery at a
      single institution between 2010 and 2015. Of this cohort, 6 patients developed
      symptomatic SEH and underwent emergency hematoma evacuation. The 6 SEH patients
      were evaluated for previously described risk factors of postoperative hematoma
      formation. In particular, postoperative blood pressure measurements were
      reviewed. The incidence of postoperative symptomatic SEH was 0.468%. Two patients
      developed SEH secondary to a nonfunctional surgical drain in the early
      postoperative period (5 or 12 h post-surgery). Preoperative and postoperative
      hypertension was observed in 4 patients who developed SEH at greater than or
      equal to 48 h following surgery. Our findings suggest that rigorous postoperative
      blood pressure control may decrease the risk of SEH.

PMID- 29178308
TI  - Effect of Intra-wound Vancomycin for Spinal Surgery: A Systematic Review and Meta
      analysis.
AB  - Intra-site prophylactic vancomycin in spine surgery is an effective method of
      decreasing the incidence of postsurgical wound infection. However, there are
      differences in the prophylactic programs used for various spinal surgeries. Thus,
      this systematic review and meta-analysis aimed to evaluate the effectiveness of
      using intra-wound vancomycin during spinal surgery and to explore the effects of
      dose-dependence and the method of administration in a subgroup analysis. A total
      of 628 citations or studies were searched in PubMed, Ovid, Web of Science, and
      Google Scholar that were published before August 2016 with the terms "local
      vancomycin", "intra-wound vancomycin", "intraoperative vancomycin", "intra-site
      vancomycin", "topical vancomycin", "spine surgery", and "spinal surgery".
      Finally, 19 retrospective cohort studies and one prospective case study were
      eligible for inclusion in the systematic review and meta-analysis. The odds of
      developing postsurgical wound infection without prophylactic local vancomycin use
      were 2.83-fold higher than the odds of experiencing wound infection with the use
      of intra-wound vancomycin (95% confidence interval, 2.03-3.95; P = 0.083; I2 =
      32.2%). The subgroup analysis including the dosage and the method of
      administration, revealed different results compared to previous research. The
      value of I2 in the 1-g group was 27.2%, which was much lower than in the 2-g
      group (I2 = 57.6%). At the same time, the value of I2 was 0.0% (P = 0.792, OR =
      2.70) when vancomycin powder was directly sprinkled into all layers of the wound.
      However, there is high heterogenicity (I2 = 60.0%, P = 0.007, OR = 2.83) when
      vancomycin powder is not exposed to the bone graft and instrumentation. There are
      differences found with the method of local application of vancomycin for reducing
      postoperative wounds and further studies are necessary, including investigations
      focusing on the dose-dependent effects during spinal or the topical
      pharmacokinetic and other orthopaedic surgeries.

PMID- 29178309
TI  - Antibiotic-loaded Bone Cement as Prophylaxis in Total Joint Replacement.
AB  - One of its most serious complications associated with arthroplasty is the
      development of infections. Although its prevalence is only between 0.5% and 3%,
      in some cases it can lead to death. Therefore, an important challenge in joint
      surgery is the prevention of infections when an arthroplasty is performed. The
      use of antibiotic-loaded cements could be a suitable tool due to numerous
      advantages. The main advantage of the use of antibiotic loading into bone cement
      derives directly from antibiotic release in the effect site, allowing achievement
      of high concentrations at the site of action, and minimal or no systemic
      toxicity. This route of administration was first described by Buchholz and
      Engelbrecht. In the case of infection treatment, this is an established method
      and its good results have been confirmed. However, its role in infection
      prevention, and, therefore, the use of these systems in clinical practice, has
      proved controversial because of the uncertainty about the development of possible
      antibiotic resistance after prolonged exposure time, their effectiveness, the
      cost of the systems, toxicity and loosening of mechanical properties. This review
      discusses all these topics, focusing on effectiveness and safety, antibiotic
      decisions, cement type, mixing method, release kinetics and future perspectives.
      The final objective is to provide the orthopaedic surgeons the right information
      in their clinical practice based on current evidence.

PMID- 29178310
TI  - A New Intraoperative Syndesmosis Instability Classification System: Utility and
      Medium-term Results in Closed Displaced Ankle Fractures.
AB  - OBJECTIVE: To investigate the utility and medium-term results of a new intra
      operative classification system for distal tibiofibular syndesmosis injury in
      ankle fractures. METHODS: Between January 2010 and January 2015, 116 patients
      diagnosed with displaced closed Weber B and C ankle fractures were treated in our
      department. The etiology of injury was 56 cases of fall-sprain, 36 of traffic
      injury, 14 of fall from a height, and 10 of multiple injuries. After fixation of
      the fibular fracture, we classify syndesmosis stability as either normal or one
      of three grades of instability using the fibular hook traction test. This
      determined further fixation selection and final syndesmosis treatment. RESULTS:
      Of 116 cases, 82 (71%) demonstrated a tibiofibular syndesmosis injury and 52
      (45%) were unstable. Twenty-six cases were type I injuries (<4 mm displacement),
      41% cases were type II injuries (4-7 mm displacement), and 3% of cases were type
      III injuries (>7 mm displacement). Types II and III are defined as unstable and
      require stabilization. Type III injuries have multiplanar instability and require
      two screws at the syndesmosis. Weber C fractures demonstrate significantly
      greater degrees of instability than Weber B fractures (chi2 = 15.50, P = 0.0014).
      All patients were followed up for 12-24 months, with no cases of non-union or
      broken screws. Good and excellent results were achieved in 93% of cases
      (according to the American Orthopaedic Foot and Ankle Society scoring system).
      CONCLUSION: The syndesmosis instability classification system provides a rational
      and efficient basis for managing syndesmosis instability. Our results from
      application of the algorithm justify its further evaluation in the treatment of
      patients with closed displaced Weber B and C ankle fractures.

PMID- 29178311
TI  - A Novel Approach for Reconstruction of Finger Neurocutaneous Defect: A Sensory
      Reverse Dorsal Digital Artery Flap from the Neighboring Digit.
AB  - OBJECTIVE: Providing soft tissue coverage for finger neurocutaneous defects
      presents aesthetic and sensory challenges. A common source for reconstruction of
      soft tissue defects of the fingers is the same finger. However, when the donor
      areas are damaged by concomitant injuries, this option is not available. The
      present study aims to reconstruct finger neurocutaneous defects using a sensory
      reverse dorsal digital artery flap from the neighboring digit and to evaluate the
      efficacy of this technique. METHODS: The study included 16 patients, with an
      average age of 34.9 years (range, 20-53 years) at the time of surgery, from May
      2010 to June 2013. The sensory reverse dorsal digital artery flap was used in all
      16 patients, who had a combination of soft tissue and digital nerve defects. The
      mean size of the soft tissue defects was 3.1 cm * 2.0 cm, and the mean flap size
      was 3.3 cm * 2.2 cm. The length of the nerve defects ranged from 1.3 to 2.5 cm
      (mean, 2.0 cm), which were reconstructed with dorsal branches of the proper
      digital nerve transfer. The active motion of the fingers (injured and donor) and
      the flap sensibility (static two-point discrimination) were measured. The
      appearance and functional recovery of the injured finger and the donor site were
      assessed using the Michigan Hand Outcomes Questionnaire. RESULTS: All flaps
      survived completely. No complications were reported, and no further flap
      debulking procedure was required. At the mean follow-up period of 24 months
      (range, 18-30 months), the mean static two-point discrimination was 6.5 mm
      (range, 5-10 mm) of the reconstructed area; the mean ranges of motions of the
      injured finger and the opposite finger at the proximal interphalangeal and distal
      interphalangeal joints were 102.2 degrees  and 103.5 degrees , and 70.3 degrees 
      and 76.5 degrees , respectively. The average ranges of motions of the
      metacarpophalangeal and proximal interphalangeal joints of the donor fingers were
      90 degrees  and 103.4 degrees , respectively. Based on the Michigan Hand Outcomes
      Questionnaire, 10 patients were strongly satisfied and 6 were satisfied with the
      functional recovery of the injured finger; however, 13 patients were strongly
      satisfied and 3 were satisfied with the appearance of the injured finger.
      CONCLUSION: The sensory reverse dorsal digital artery flap from the neighboring
      digit, based on the dorsal branch of the digital artery, is an effective and
      additional option for finger neurocutaneous defect reconstruction when use of the
      local and regional flaps is not feasible.

PMID- 29178312
TI  - Total Hip Arthroplasty in Hemophilia Patients: A Mid-term to Long-term Follow-up.
AB  - OBJECTIVE: To report the results of mid-term to long-term follow-up after primary
      total hip arthroplasty (THA) in hemophiliacs and to hypothesize that THA can
      provide satisfactory outcomes in these patients. METHODS: Twenty-four primary THA
      performed in 21 hemophilia patients between 2002 and 2012 were reviewed
      retrospectively, including 20 cases of hemophilia A and 1 case of hemophilia B.
      The standard lateral approach was used for all implantations. Substitution
      therapy for factor VIII and activated prothrombin complex concentrates were
      administered to patients with hemophilia A and B, respectively. Total and hidden
      blood loss were calculated. Outcomes were assessed using the Harris hip score
      before surgery and at the final follow-up visit. Complications were recorded by
      clinical and radiographic assessment and then compared to those in previous
      reports. RESULTS: The mean follow-up period was 113 months (range, 5-15 years).
      The average total blood loss was 3559 mL (range, 1494-7506 mL). The mean amount
      of red blood cell (RBC) transfusion was 4.4 U (range, 0-14 U). The mean amount of
      clotting factor used in the perioperative period for management of hemophilia was
      14 031.3 U (range, 8100-25 200 U). Harris hip scores improved from 37 points
      (range, 15-81) before surgery to 90 points (range, 70-96) at the last follow-up.
      No signs of loosening, infection or other complications of the implant components
      occurred after discharge. The overall survivorship of the implants was 100% for
      all patients, and no revision surgery was performed. CONCLUSIONS: With modern
      techniques and hematological management, THA in patients with hemophilia leads to
      significant improvement in joint function with a relatively low incidence of
      complications. Increased blood loss and substitution therapy have no obvious
      negative influences on the mid-term to long-term results of THA.

PMID- 29178313
TI  - Association of Insulin-like Growth Factor-1, Bone Mass and Inflammation to Low
      energy Distal Radius Fractures and Fracture Healing in Elderly Women Attending
      Emergency Care.
AB  - OBJECTIVE: Elderly patients suffer fractures through low-energy mechanisms. The
      distal radius is the most frequent fracture localization. Insulin-like growth
      factor-1 (IGF1) plays an important role in the maintenance of bone mass and its
      levels decline with advancing age and in states of malnutrition. Our aim was to
      investigate the association of IGF1 levels, bone mass, nutritional status, and
      inflammation to low-energy distal radius fractures and also study if fracture
      healing is influenced by IGF1, nutritional status, and inflammation. METHODS:
      Postmenopausal women, 55 years or older, with low-energy distal radius fractures
      occurring due to falling on slippery ground, indoors or outdoors, were recruited
      in the emergency department (ED) and followed 1 and 5 weeks after the initial
      trauma with biomarkers for nutritional status and inflammation. Fractures were
      diagnosed according to standard procedure by physical examination and X-ray. All
      patients were conservatively treated with plaster casts in the ED. Patients who
      needed interventions were excluded from our study. Fracture healing was evaluated
      from radiographs. Fracture healing assessment was made with a five-point scale
      where the radiological assessment included callus formation, fracture line, and
      stage of union. Blood samples were taken within 24 h after fracture and analyzed
      in the routine laboratory. Bone mineral density (BMD) was measured by dual-energy
      X-ray absorptiometry (DXA). RESULTS: Thirty-eight Caucasian women, aged 70.5 +/-
      8.9 years (mean +/- SD) old, were recruited. Nutritional status, as evaluated by
      albumin (40.3 +/- 3.1 g/L), IGF1 (125.3 +/- 39.9 MUg/L), body mass index (26.9 +/
      3.6 kg/m2 ), arm diameter (28.9 +/- 8.9 cm), and arm skinfold (2.5 +/- 0.7 cm),
      was normal. A positive correlation was found between IGF1 at visit 1 and the
      lowest BMD for hip, spine, or radius (r = 0.39, P = 0.04). High sensitive C
      reactive protein (hsCRP) and leukocytes were higher at the fracture event
      compared to 5 weeks later (P = 0.07 and P < 0.001, respectively). Fracture
      healing parameters (i.e. callus formation, fracture line, and stage of union)
      were positively correlated with the initial leukocyte count and to difference in
      thrombocyte count between visit 1 and 3. CONCLUSIONS: In elderly women with low
      energy distal radius fractures, an association between IGF1 and lowest measures
      of BMD was found, indicating that low IGF1 could be an indirect risk factor for
      fractures. Fracture healing was associated with initial leukocytosis and a lower
      thrombocyte count, suggesting that inflammation and thrombocytes are important
      components in fracture healing.

PMID- 29178314
TI  - Perforated giant mycotic aneurysm of mitral valve in a drug-addicted young man:
      Rare complication of infective endocarditis.
AB  - Infective endocarditis (IE) affects patients at high clinical risk and may
      present as an acute and rapidly progressive, subacute or chronic infection.
      Transthoracic and transesophageal echocardiography represent the key diagnostic
      method in IE diagnosis. In particular, three-dimensional transesophageal
      echocardiography represents the imaging technique that allows to establish with
      adequate accuracy dimensions, shape, and localization of endocarditis
      vegetations. In our case, we show a huge vermiform mycotic aneurysm in an
      immunodeficient young drug-addicted man with severe mitral valve regurgitation
      and the additive value of three-dimensional transesophageal echocardiography in
      this specific clinical setting.

PMID- 29178315
TI  - 3D aggregate culture improves metabolic maturation of human pluripotent stem cell
      derived cardiomyocytes.
AB  - Three-dimensional (3D) cultures of human pluripotent stem cell derived
      cardiomyocytes (hPSC-CMs) hold great promise for drug discovery, providing a
      better approximation to the in vivo physiology over standard two-dimensional (2D)
      monolayer cultures. However, the transition of CM differentiation protocols from
      2D to 3D cultures is not straightforward. In this work, we relied on the
      aggregation of hPSC-derived cardiac progenitors and their culture under agitated
      conditions to generate highly pure cardiomyocyte aggregates. Whole-transcriptome
      analysis and 13 C-metabolic flux analysis allowed to demonstrate at both
      molecular and fluxome levels that such 3D culture environment enhances metabolic
      maturation of hiPSC-CMs. When compared to 2D, 3D cultures of hiPSC-CMs displayed
      down-regulation of genes involved in glycolysis and lipid biosynthesis and
      increased expression of genes involved in OXPHOS. Accordingly, 3D cultures of
      hiPSC-CMs had lower fluxes through glycolysis and fatty acid synthesis and
      increased TCA-cycle activity. Importantly, we demonstrated that the 3D culture
      environment reproducibly improved both CM purity and metabolic maturation across
      different hPSC lines, thereby providing a robust strategy to derive enriched hPSC
      CMs with metabolic features closer to that of adult CMs.

PMID- 29178316
TI  - A comparison of accuracy validation methods for genomic and pedigree-based
      predictions of swine litter size traits using Large White and simulated data.
AB  - The objective of this study was to compare and determine the optimal validation
      method when comparing accuracy from single-step GBLUP (ssGBLUP) to traditional
      pedigree-based BLUP. Field data included six litter size traits. Simulated data
      included ten replicates designed to mimic the field data in order to determine
      the method that was closest to the true accuracy. Data were split into training
      and validation sets. The methods used were as follows: (i) theoretical accuracy
      derived from the prediction error variance (PEV) of the direct inverse (iLHS),
      (ii) approximated accuracies from the accf90(GS) program in the BLUPF90 family of
      programs (Approx), (iii) correlation between predictions and the single-step
      GEBVs from the full data set (GEBVFull ), (iv) correlation between predictions
      and the corrected phenotypes of females from the full data set (Yc ), (v)
      correlation from method iv divided by the square root of the heritability (Ych )
      and (vi) correlation between sire predictions and the average of their daughters'
      corrected phenotypes (Ycs ). Accuracies from iLHS increased from 0.27 to 0.37
      (37%) in the Large White. Approximation accuracies were very consistent and close
      in absolute value (0.41 to 0.43). Both iLHS and Approx were much less variable
      than the corrected phenotype methods (ranging from 0.04 to 0.27). On average,
      simulated data showed an increase in accuracy from 0.34 to 0.44 (29%) using
      ssGBLUP. Both iLHS and Ych approximated the increase well, 0.30 to 0.46 and 0.36
      to 0.45, respectively. GEBVFull performed poorly in both data sets and is not
      recommended. Results suggest that for within-breed selection, theoretical
      accuracy using PEV was consistent and accurate. When direct inversion is
      infeasible to get the PEV, correlating predictions to the corrected phenotypes
      divided by the square root of heritability is adequate given a large enough
      validation data set.

PMID- 29178317
TI  - Community Program Improves Quality of Life and Self-Management in Older Adults
      with Diabetes Mellitus and Comorbidity.
AB  - OBJECTIVES: To compare the effect of a 6-month community-based intervention with
      that of usual care on quality of life, depressive symptoms, anxiety, self
      efficacy, self-management, and healthcare costs in older adults with type 2
      diabetes mellitus (T2DM) and 2 or more comorbidities. DESIGN: Multisite, single
      blind, parallel, pragmatic, randomized controlled trial. SETTING: Four
      communities in Ontario, Canada. PARTICIPANTS: Community-dwelling older adults
      (>=65) with T2DM and 2 or more comorbidities randomized into intervention (n =
      80) and control (n = 79) groups (N = 159). INTERVENTION: Client-driven,
      customized self-management program with up to 3 in-home visits from a registered
      nurse or registered dietitian, a monthly group wellness program, monthly provider
      team case conferences, and care coordination and system navigation. MEASUREMENTS:
      Quality-of-life measures included the Physical Component Summary (PCS, primary
      outcome) and Mental Component Summary (MCS, secondary outcome) scores of the
      Medical Outcomes Study 12-item Short-Form Health Survey (SF-12). Other secondary
      outcome measures were the Generalized Anxiety Disorder Scale, Center for
      Epidemiologic Studies Depression Scale (CES-D-10), Summary of Diabetes Self-Care
      Activities (SDSCA), Self-Efficacy for Managing Chronic Disease, and healthcare
      costs. RESULTS: Morbidity burden was high (average of eight comorbidities).
      Intention-to-treat analyses using analysis of covariance showed a group
      difference favoring the intervention for the MCS (mean difference = 2.68, 95%
      confidence interval (CI) = 0.28-5.09, P = .03), SDSCA (mean difference = 3.79,
      95% CI = 1.02-6.56, P = .01), and CES-D-10 (mean difference = -1.45, 95% CI = 
      0.13 to -2.76, P = .03). No group differences were seen in PCS score, anxiety,
      self-efficacy, or total healthcare costs. CONCLUSION: Participation in a 6-month
      community-based intervention improved quality of life and self-management and
      reduced depressive symptoms in older adults with T2DM and comorbidity without
      increasing total healthcare costs.

PMID- 29178318
TI  - Thyroid cancer patients receiving an interdisciplinary team-based care approach
      (ITCA-ThyCa) appear to display better outcomes: Program evaluation results
      indicating a need for further integrated care and support.
AB  - BACKGROUND: Thyroid cancer (ThyCa) is generally associated with a favorable
      prognosis and excellent surgical outcomes. Consequently, its treatment is
      medically focused and current guidelines recommend interdisciplinary care
      including access to a nurse for complex cases alone. To date, no studies have
      evaluated the need for and impact of an Interdisciplinary Team-based Care
      Approach (ITCA-ThyCa) for general thyroid cancer patients, including a dedicated
      nurse as part of a larger interdisciplinary team, as well as patient-reported
      outcomes, as is recommended worldwide in cancer care. Our aim was to evaluate
      such a program. METHODS: The ITCA-ThyCa was evaluated within a quasi-experimental
      design using the Centers for Disease Control Framework for Program Evaluation,
      including process and outcome measures. Patients eligible were adults with a
      biopsy indicating confirmed or highly suspicious ThyCa (TNM-Classification +
      Bethesda score of V/VI). The intervention group (IG) received ITCA-ThyCa and the
      comparison group (CG), usual care alone. RESULTS: In our sample comprised of 200
      participants (122 IG; 78 CG), ITCA-ThyCa patients appeared to show significantly
      better outcomes than CG patients, namely, higher levels of overall well-being (P
      = .001) and fewer physical (P = .003) and practical (P = .003) issues and
      concerns. More satisfied with their overall care (P = .028), including care
      coordination (P = .049), they reported their health care provider as more
      approachable (P = .007), respectful (P = .005), and trustworthy (P = .077; trend)
      and were more likely to recommend their hospital (P = .02). Ninety-eight percent
      of IG patients recommended ITCA-ThyCa. CONCLUSION: Data from our program
      illustrates that hospital resources should not be allocated based on medical
      trajectory alone and challenges the idea that ThyCa is "straightforward." ThyCa
      patients seem to experience symptom distress at a level comparable to-or
      exceeding-that of general oncological patients despite their promising medical
      outcomes, indicating that better integrated care and support are in order.

PMID- 29178319
TI  - Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal
      muscle mass regulation.
AB  - AIM: Based upon a microarray assay, we have identified that triiodothyronine (T3)
      upregulates MDM2 gene expression in the rat skeletal muscle. As MDM2 protein is
      an E3 ligase, we hypothesized that this enzyme could play a role in T3 effects on
      skeletal muscle mass control. METHODS: To test our hypothesis, male rats (2
      months old) were randomly assigned into the following groups: intact controls,
      treated with 20 physiological doses of T3 for 0.5, 1 and 7 days, or with 5, 20
      and 50 physiological doses of T3 for 7 days. For in vitro experiments, myotubes
      and C2C12 cells were treated with T3 for 3 days. RESULTS: After validation of the
      microarray finding throughout RT-PCR and confirmation that T3 induces increases
      in MDM2 protein expression in a dose-dependent manner, we observed that MDM2 was
      upregulated by T3 exclusively in fibre type I. Moreover, detailed histological
      evaluation showed that MDM2 overexpression distributes punctiformily along the
      cross section of the fibre and also inside nuclei. MDM2 colocalizes with PAX7 in
      control muscle and T3 downregulates this myogenic factor. Pharmacological
      inhibition of MDM2 in cultured myotubes caused a severe decrease in their
      diameter (~35%, P < .001 vs Control), enhancing the effect of T3 (from ~12% to
      ~35%, P < .001) alone upon myotube diameter and mRNA levels of atrogenes.
      Finally, we observed that FOXO3 (MDM2 target) is kept outside the nucleus under
      T3 stimulation. CONCLUSION: Our results indicate that MDM2 might be involved in
      the pro-trophic effects of T3 in skeletal muscle.

PMID- 29178320
TI  - Low-oxygen conditions promote synergistic increases in chondrogenesis during co
      culture of human osteoarthritic stem cells and chondrocytes.
AB  - There has been increased interest in co-cultures of stem cells and chondrocytes
      for cartilage tissue engineering as there are the limitations associated with
      using either cell type alone. Drawbacks associated with the use of chondrocytes
      include the limited numbers of cells available for isolation from damaged or
      diseased joints, their dedifferentiation during in vitro expansion, and a
      diminished capacity to synthesise cartilage-specific extracellular matrix
      components with age and disease. This has motivated the use of adult stem cells
      with either freshly isolated or culture-expanded chondrocytes for cartilage
      repair applications; however, the ideal combination of cells and environmental
      conditions for promoting robust chondrogenesis remains unclear. In this study, we
      compared the effect of combining a small number of freshly isolated or culture
      expanded human chondrocytes with infrapatellar fat pad-derived stem cells (FPSCs)
      from osteoarthritic donors on chondrogenesis in altered oxygen (5% or 20%) and
      growth factor supplementation (TGF-beta3 only or TGF-beta3 and BMP-7) conditions.
      Both co-cultures, but particularly those including freshly isolated chondrocytes,
      were found to promote cell proliferation and enhanced matrix accumulation
      compared to the use of FPSCs alone, resulting in the development of a tissue that
      was compositionally more similar to that of the native articular cartilage. Local
      oxygen levels were found to impact chondrogenesis in co-cultures, with more
      robust increases in proteoglycan and collagen deposition observed at 5% O2 .
      Additionally, collagen type I synthesis was suppressed in co-cultures maintained
      at low-oxygen conditions. This study demonstrates that a co-culture of freshly
      isolated human chondrocytes and FPSCs promotes robust chondrogenesis and thus is
      a promising cell combination for cartilage tissue engineering.

PMID- 29178322
TI  - Literacy analysis of National Comprehensive Cancer Network patient guidelines for
      the most common malignancies in the United States.
AB  - BACKGROUND: Cancer information is of critical interest to the public. The
      National Comprehensive Cancer Network (NCCN) offers a series of comprehensive
      patient guidelines on the management of the most common cancer diagnoses. This
      study was aimed at assessing the health literacy demands of NCCN patient
      guidelines for the most common malignancies in the United States. METHODS: The
      American Cancer Society's most common malignancies by annual incidence in the
      United States and their corresponding NCCN patient guidelines were identified.
      Four validated tools were used to evaluate literacy levels: 1) the Simple Measure
      of Gobbledygook, 2) the Peter Mosenthal and Irwin Kirsch readability formula
      (PMOSE/IKIRSCH), 3) the Patient Education Materials Assessment Tool (PEMAT), and
      4) the Clear Communication Index from the Centers for Disease Control and
      Prevention (CDC). RESULTS: The average reading grade level was 10.3, which was
      higher than the recommended 6th-grade level. The average PMOSE/IKIRSCH score was
      11; this corresponded to moderate complexity and required some college-level
      education for interpretation. Only 1 tool, the PEMAT, yielded scores above the
      benchmarks for high-quality materials. The PEMAT's understandability,
      actionability, and overall scores were 94%, 83%, and 91%, respectively. The
      average CDC index was 85%, which was below the recommended 90% for an appropriate
      health literacy demand. CONCLUSIONS: Overall, the assessment indicates high
      demand scores for the readability and complexity of the NCCN patient guidelines
      and thus that the materials are not quite suitable for the general US adult
      population. Further input from patient focus groups to address appropriateness
      and usefulness is critical. Cancer 2018;124:769-74. (c) 2017 American Cancer
      Society.

PMID- 29178321
TI  - Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting
      eating behavior.
AB  - Glucose is a key modulator of feeding behavior. By acting in peripheral tissues
      and in the central nervous system, it directly controls the secretion of hormones
      and neuropeptides and modulates the activity of the autonomic nervous system.
      GLUT2 is required for several glucoregulatory responses in the brain, including
      feeding behavior, and is localized in the hypothalamus and brainstem, which are
      the main centers that control this behavior. In the hypothalamus, GLUT2 has been
      detected in glial cells, known as tanycytes, which line the basal walls of the
      third ventricle (3V). This study aimed to clarify the role of GLUT2 expression in
      tanycytes in feeding behavior using 3V injections of an adenovirus encoding a
      shRNA against GLUT2 and the reporter EGFP (Ad-shGLUT2). Efficient in vivo GLUT2
      knockdown in rat hypothalamic tissue was demonstrated by qPCR and Western blot
      analyses. Specificity of cell transduction in the hypothalamus and brainstem was
      evaluated by EGFP-fluorescence and immunohistochemistry, which showed EGFP
      expression specifically in ependymal cells, including tanycytes. The altered mRNA
      levels of both orexigenic and anorexigenic neuropeptides suggested a loss of
      response to increased glucose in the 3V. Feeding behavior analysis in the fasting
      feeding transition revealed that GLUT2-knockdown rats had increased food intake
      and body weight, suggesting an inhibitory effect on satiety. Taken together,
      suppression of GLUT2 expression in tanycytes disrupted the hypothalamic
      glucosensing mechanism, which altered the feeding behavior.

PMID- 29178323
TI  - Diverse Structures Based on a Heptanuclear Cobalt Cluster with 0D to 3D Metal
      Organic Frameworks: Magnetism and Application in Batteries.
AB  - Polymetallic complexes with interesting multifunctions have attracted extensive
      investigation. Synthesized through the use of different cobalt salt anions and
      solvents, five complexes, namely [CoII4 CoIII3 (H2 L)3 Cl5 (MeOH)] (1), [CoII4
      CoIII3 (H2 L)3 (CH3 COO)4 (HCOO)?H2 O]n (2), [CoII4 CoIII3 (H2 L)3 (HCOO)4 (NO3
      )?2H2 O]n (3), [CoII4 CoIII3 (H2 L)3 (bda)(CH3 COO)4 ?2H2 O]n (4), and [CoII4
      CoIII3 (H2 L)3 (ipa)(HCOO)3 (dmf)?H2 O]n (5) (H6 L=bis-tris propane; BDA=biphenyl
      4,4'-dicarboxylic acid; IPA=isophthalic acid; DMF=N,N-dimethylformamide), based
      on the heptanuclear {CoII4 CoIII3 } cluster with structures from 0D to 3D metal
      organic frameworks (MOFs) have been solvothermally synthesized. Compound 1 is the
      first 0D heptanuclear cluster based on H6 L. Compound 2 crystallizes in the
      chiral space group P21 21 21 and consists of a 1D chiral helical chain. Complex 3
      exhibits a 3D network structure. Compound 4 possesses a 1D zigzag-like chain
      structure. Finally, compound 5 was obtained as a 3D microporous structure.
      Compounds 1, 3, and 4 display dominant ferrimagnetic interactions whereas
      compounds 2 and 5 exhibit antiferromagnetic interactions. Moreover, the Co3 O4
      prepared by calcining compound 2 presents a reversible capacity of 1122.9 mA h g
      1 at 0.2 A g-1 after 100 cycles and an excellent rate capability, which suggests
      that coordination compounds with a 1D chain structure are outstanding precursors
      for preparing anode materials for lithium ion batteries.

PMID- 29178324
TI  - Effect of LSR polymorphism on blood lipid levels and age-specific epistatic
      interaction with the APOE common polymorphism.
AB  - The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B
      and ApoE receptor that participates in the removal of triglyceride-rich
      lipoproteins during the postprandial phase. LSR gene is located upstream of APOE,
      an important risk factor for cardiovascular disease (CVD). Since the APOE common
      polymorphism significantly affects the variability of lipid metabolism, this
      study aimed to determine the potential impact of a functional SNP rs916147 in LSR
      gene on lipid traits in healthy subjects and to investigate potential epistatic
      interaction between LSR and APOE. Unrelated healthy adults (N = 432) and children
      (N = 328, <18 years old) from the STANISLAS Family Study were used. Age-specific
      epistasis was observed between APOE and LSR, reversing the protective effect of
      APOE epsilon2 allele on cholesterol, ApoE and low-density lipoprotein levels
      (beta: .114, P: .777 * 10-8 , beta: .125, P: .639 * 10-3 , beta: .059, P: .531 *
      10-3 , respectively). This interaction was verified in an independent adult
      population (n = 1744). These results highlight the importance of the LSR
      polymorphism and reveal the existence of complex molecular links between LSR and
      ApoE for the regulation of lipid levels, revealing potential new pathways of
      interest in type III hyperlipidemia and its involvement in CVD pathology.

PMID- 29178325
TI  - The spectrum of bleeding in women and girls with haemophilia B.
AB  - Although hemophilia B affects 1 in 25,000 males there may be 3 female hemophilia
      B carriers per affected male. This clinical review highlights the unique
      challenges faced by hemophilia B carriers including the under-recognition of
      bleeding symptoms associated with and without FIX deficiency, discrepancies in
      correlation between genotype and bleeding phenotype and therapeutic
      considerations utilizing clinical vignettes of common scenarios.

PMID- 29178326
TI  - Anatomy of genital reaffirmation surgery (male-to-female): Vaginoplasty using
      penile skin graft with scrotal flaps.
AB  - Gender reaffirmation surgery is the final step in an individual's transition to
      their preferred gender. A clear understanding of the anatomy pertinent to this
      procedure is essential by the surgeon and patient. In male-to-female
      transgenders, female genitalia is constructed using the individual's penile skin
      to form the neovaginal canal and their scrotal skin folds post orchiectomy to
      create the labia majora. The surgical precursors of the remaining anatomical
      structures of the female genitalia are as follows: the clitoris is crafted from
      the glans penis and hence retains its innervation, the labia minora is formed
      using excess penile skin tissue, and the long male urethra is shortened to that
      of its feminine counterpart. The main goal of these reconstructive methods is to
      create a functionally and aesthetically acceptable vagina and vulva, as well as
      normal voiding function and satisfactory sexual function. Surgical text
      descriptions were enhanced by the creation of new anatomic illustrations. Review
      of the relevant literature regarding the anatomy, procedure development, and
      outcomes is presented. Vaginoplasty utilizing penile skin grafts with scrotal
      flaps provides an aesthetically acceptable and psychologically satisfying results
      with normal voiding and sexual function. An advantage includes preserved
      erogenous sensation. Complications can arise, including chronic inflammation and
      fistula formation. The anatomy of vaginoplasty using penile skin grafts with
      scrotal flaps supports patients seeking male-to-female gender reaffirmation
      surgery. Clin. Anat. 31:140-144, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178327
TI  - Generalized verrucosis caused by various human papillomaviruses in a patient with
      GATA2 deficiency.

PMID- 29178328
TI  - Mineralocorticoid receptor blockade improves glucocorticoid-induced skin atrophy
      but partially ameliorates anti-inflammatory actions in an irritative model in
      human skin explants.
AB  - We recently demonstrated that blockade of the mineralocorticoid receptor (MR)
      effectively ameliorated GC-induced skin atrophy in healthy human skin explants
      and epidermal MR knockout mice. However, whether MR blockade improves the
      therapeutic index of glucocorticoids (GCs) in skin pathology was not
      investigated. We assessed the effects of GCs, MR antagonists (MRA) or both, in
      SDS-treated human skin explants. All treatments restored SDS-augmented epidermal
      thickness but only GC plus MRA restored the expression of COL1A1. However, MRA
      alone or in combination with GCs may exert a dual role in regulating inflammatory
      cytokines. Thus, although combined treatment may be beneficial to improve
      irritative skin, extensive in vivo testing is required to establish whether the
      anti-inflammatory effects of GCs are maintained in the presence of MRA.

PMID- 29178329
TI  - Publish, perish, or put patients first?

PMID- 29178330
TI  - Translational approaches to restoring mitochondrial function in Parkinson's
      disease.
AB  - There is strong evidence of a key role for mitochondrial dysfunction in both
      sporadic and all forms of familial Parkinson's disease (PD). However, none of the
      clinical trials carried out with putative mitochondrial rescue agents have been
      successful. Firm establishment of a wet biomarker or a reliable readout from
      imaging studies detecting mitochondrial dysfunction and reflecting disease
      progression is also awaited. We will provide an overview of our current knowledge
      about mitochondrial dysfunction in PD and related drug screens. We will also
      summarise previously undertaken mitochondrial wet biomarker studies and relevant
      imaging studies with particular focus on 31P-MRI spectroscopy. We will conclude
      with an overview of clinical trials which tested putative mitochondrial rescue
      agents in PD patients.

PMID- 29178331
TI  - Response to: bullous pemphigoid inguinalis?

PMID- 29178332
TI  - Eating disorders in people with Type 1 diabetes: experiential perspectives of
      both clients and healthcare professionals.
AB  - AIMS: To explore the experiential perspective of people with Type 1 diabetes
      mellitus and eating disorders and that of the healthcare professionals treating
      them, and to understand the experience of both sides to inform future development
      of healthcare services. METHODS: Participants were recruited from Diabetics with
      Eating Disorders (a national UK charity), and through professional networks. Nine
      partially/fully recovered individuals with Type 1 diabetes and eating disorders
      and eight healthcare professionals participated in semi-structured interviews
      carried out by medically trained researchers. Data were transcribed and coded
      using a six-stage framework of thematic analysis. RESULTS: Four superordinate
      themes and several subordinate themes emerged from the Type 1 diabetes and eating
      disorders dataset: (1) perceptions surrounding service provision; (2) reflections
      on the recovery process; (3) the experiential perspective of living with Type 1
      diabetes and an eating disorder; and (4) support mechanisms. Healthcare
      professional data elicited three superordinate themes and several subordinate
      themes: (1) service provision; (2) personal insight and reflection of
      professional role; and (3) challenges of working with dual diagnoses. CONCLUSION:
      People with Type 1 diabetes and eating disorders and their healthcare
      professionals provided insight into healthcare services from the patient and care
      delivery perspectives. There was general agreement from both groups that a
      multidisciplinary, collaborative (family inclusive), clinical approach to
      treatment is important, as well as adequate training opportunities for service
      providers. These findings may help to inform development strategies for
      multidisciplinary care approaches to Type 1 diabetes complicated by eating
      disorders.

PMID- 29178333
TI  - Model-Based Reverse Translation Between Veterinary and Human Medicine: The One
      Health Initiative.
AB  - There is growing concern about the limitations of rodent models with regard to
      recapitulation of human disease pathogenesis. Computational modeling of data from
      humans and animals sharing similar diseases provides an opportunity for parallel
      drug development in human and veterinary medicine. This "reverse translational"
      approach needs to be supported by continuing efforts to refine the in silico
      tools that allow extrapolation of results between species.

PMID- 29178334
TI  - Suppression of oxidative phosphorylation confers resistance against bevacizumab
      in experimental glioma.
AB  - Although bevacizumab initially shows high response rates in gliomas and other
      tumours, therapy resistance usually develops later. Because anti-angiogenic
      agents are supposed to induce hypoxia, we asked whether rendering glioma cells
      independent of oxidative phosphorylation modulates their sensitivity against
      hypoxia and bevacizumab. LNT-229 glioma cells without functional mitochondria
      (rho0 ) and control (rho+ ) cells were generated. LNT-229 rho0 -cells displayed
      reduced expression of oxidative phosphorylation-related genes and diminished
      oxygen consumption. Conversely, glycolysis was up-regulated in these cells, as
      shown by increased lactate production and stronger expression of glucose
      transporter-1 and lactate dehydrogenase-A. However, hypoxia-induced cell death in
      vitro was nearly completely abolished in the LNT-229 rho0 -cells, these cells
      were more sensitive towards glucose restriction and the treatment with the
      glycolysis inhibitor 2-deoxy-D-glucose. In an orthotopic mouse xenograft
      experiment, bevacizumab induced hypoxia as reflected by elevated Hypoxia
      inducible factor 1-alpha staining in both, rho+ - and rho0 -tumours. However, it
      prolonged survival only in the mice bearing rho+ -tumours (74 days vs. 105 days,
      p = 0.024 log-rank test) and had no effect on survival in mice carrying LNT-229
      rho0 -tumours (75 days vs. 70 days, p = 0.52 log-rank test). Interestingly,
      inhibition of glycolysis in vivo with 2-deoxy-D-glucose re-established
      sensitivity of rho0 -tumours against bevacizumab (98 days vs. 80 days, p =
      0.0001). In summary, ablation of oxidative phosphorylation in glioma cells leads
      to a more glycolytic and hypoxia-resistant phenotype and is sufficient to induce
      bevacizumab-refractory tumours. These results add to increasing evidence that a
      switch towards glycolysis is one mechanism how tumour cells may evade anti
      angiogenic treatments and suggest anti-glycolytic strategies as promising
      approaches to overcome bevacizumab resistance.

PMID- 29178335
TI  - A General Synthesis of Porous Carbon Nitride Films with Tunable Surface Area and
      Photophysical Properties.
AB  - Graphitic carbon nitride (g-CN) has emerged as a promising material for energy
      related applications. However, exploitation of g-CN in practical devices is still
      limited owing to difficulties in fabricating g-CN films with adjustable
      properties and high surface area. A general and simple pathway is reported to
      grow highly porous and large-scale g-CN films with controllable chemical and
      photophysical properties on various substrates using the doctor blade technique.
      The growth of g-CN films, ascribed to the formation of a supramolecular paste,
      comprises g-CN monomers in ethylene glycol, which can be cast on different
      substrates. The g-CN composition, porosity, and optical properties can be tuned
      by the design of the supramolecular paste, which upon calcination results in a
      continuous porous g-CN network. The strength of the porous structure is
      demonstrated by high electrochemically active surface area, excellent dye
      adsorption and photoelectrochemical and photodegradation properties.

PMID- 29178336
TI  - Taking error into account when fitting models using Approximate Bayesian
      Computation.
AB  - Stochastic computer simulations are often the only practical way of answering
      questions relating to ecological management. However, due to their complexity,
      such models are difficult to calibrate and evaluate. Approximate Bayesian
      Computation (ABC) offers an increasingly popular approach to this problem, widely
      applied across a variety of fields. However, ensuring the accuracy of ABC's
      estimates has been difficult. Here, we obtain more accurate estimates by
      incorporating estimation of error into the ABC protocol. We show how this can be
      done where the data consist of repeated measures of the same quantity and errors
      may be assumed to be normally distributed and independent. We then derive the
      correct acceptance probabilities for a probabilistic ABC algorithm, and update
      the coverage test with which accuracy is assessed. We apply this method, which we
      call error-calibrated ABC, to a toy example and a realistic 14-parameter
      simulation model of earthworms that is used in environmental risk assessment. A
      comparison with exact methods and the diagnostic coverage test show that our
      approach improves estimation of parameter values and their credible intervals for
      both models.

PMID- 29178337
TI  - Roll-to-Roll Production of Layer-Controlled Molybdenum Disulfide: A Platform for
      2D Semiconductor-Based Industrial Applications.
AB  - A facile methodology for the large-scale production of layer-controlled MoS2
      layers on an inexpensive substrate involving a simple coating of single source
      precursor with subsequent roll-to-roll-based thermal decomposition is developed.
      The resulting 50 cm long MoS2 layers synthesized on Ni foils possess excellent
      long-range uniformity and optimum stoichiometry. Moreover, this methodology is
      promising because it enables simple control of the number of MoS2 layers by
      simply adjusting the concentration of (NH4 )2 MoS4 . Additionally, the capability
      of the MoS2 for practical applications in electronic/optoelectronic devices and
      catalysts for hydrogen evolution reaction is verified. The MoS2 -based field
      effect transistors exhibit unipolar n-channel transistor behavior with electron
      mobility of 0.6 cm2 V-1 s-1 and an on-off ratio of ~103. The MoS2 -based visible
      light photodetectors are fabricated in order to evaluate their photoelectrical
      properties, obtaining an 100% yield for active devices with significant
      photocurrents and extracted photoresponsivity of ~22 mA W-1 . Moreover, the MoS2
      layers on Ni foils exhibit applicable catalytic activity with observed
      overpotential of ~165 mV and a Tafel slope of 133 mV dec-1 . Based on these
      results, it is envisaged that the cost-effective methodology will trigger actual
      industrial applications, as well as novel research related to 2D semiconductor
      based multifaceted applications.

PMID- 29178338
TI  - Disorder- and Treatment-Specific Therapeutic Competence Scales for Posttraumatic
      Stress Disorder Intervention: Development and Psychometric Properties.
AB  - Although the assessment of therapeutic competence in psychotherapy research is
      essential for examining its possible associations with treatment outcomes, it is
      often neglected due to high costs and a lack of valid instruments. This study
      aimed to develop two therapeutic competence scales that assess disorder-specific
      and treatment-specific therapeutic competence, and to examine these scales'
      psychometric properties along with those of the already established Cognitive
      Therapy Scale (CTS) in a posttraumatic stress disorder (PTSD) sample. Using an
      inductive procedure, two rating scales for assessing disorder-specific and
      treatment-specific competence were constructed. The psychometric properties of
      these scales and those of the CTS were assessed in a sample of 30 videotaped
      sessions of eight patients from a multicenter study in which PTSD related to
      child abuse was treated using cognitive processing therapy. Two raters assessed
      therapeutic competence in 30 videotaped psychotherapy sessions. Interrater
      reliability, internal consistency, and content validity were determined. The
      scales (all items and total scores) demonstrated good to excellent interrater
      reliability, intraclass correlation coefficients (ICCs) = .67 to .97, and
      internal consistency, Cronbach's alpha = .73 to .92. The PTSD experts' ratings
      confirmed good internal validity. We found statistically significant associations
      with therapeutic adherence, r = .62 to .85; p < .001; and therapeutic alliance, r
      = .47, p < .001. These preliminary data imply that the two newly developed
      competence scales and the CTS can be reliably used to assess different types of
      therapeutic competence in PTSD samples and may be useful as possible predictors
      of treatment outcomes.

PMID- 29178339
TI  - Chemical Constituents of Sweetpotato Genotypes in Relation to Textural
      Characteristics of Processed French Fries.
AB  - : Sweetpotato French fries (SPFF) are growing in popularity, however limited
      information is available on SPFF textural properties in relation to chemical
      composition. This study investigated the relationship between chemical components
      of different sweetpotato varieties and textural characteristics of SPFF. Sixteen
      sweetpotato genotypes were evaluated for (1) chemical constituents; (2)
      instrumental and sensory textural properties of SPFF; and (3) the relationship
      between chemical components, instrumental measurements, and sensory attributes.
      Dry matter (DM), alcohol-insoluble solids (AIS), starch, sugar, and oil content,
      and also alpha- and beta-amylase activities were quantified in raw sweetpotatoes
      and SPFF. Peak force and overall hardness describing instrumental textural
      properties of SPFF were measured using a texture analyzer. Descriptive sensory
      analysis was conducted and 10 attributes were evaluated by a trained panel.
      Results showed that DM, AIS, and starch content in raw sweetpotatoes were
      significantly correlated (P < 0.05) with instrumental peak force and overall
      hardness (r = 0.41 to 0.68), and with sensory surface roughness, hardness,
      fracturability, and crispness (r = 0.63 to 0.90). Total sugar content in raw
      sweetpotatoes was positively correlated with sensory smoothness and moistness (r
      = 0.77), and negatively correlated with instrumental peak force and overall
      hardness (r = -0.62 to -0.69). Instrumental measurements were positively
      correlated with sensory attributes of hardness, fracturability, and crispness (r
      = 0.68 to 0.96) and negatively correlated with oiliness, smoothness, moistness,
      and cohesiveness (r = -0.61 to -0.91). Therefore, DM, AIS, starch, and total
      sugar contents and instrumental measurements could be used as indicators to
      evaluate sweetpotato genotypes for SPFF processing. PRACTICAL APPLICATION: In
      recent years, sweetpotato French fries (SPFF) have grown in popularity, but
      limited information is available on SPFF textural properties in relation to the
      differences in chemical constituents among sweetpotato varieties. This study
      demonstrated that sensory texture attributes of SPFF varied widely and were
      significantly correlated with chemical components such as dry matter, starch, and
      total sugar contents of raw sweetpotatoes and instrumental texture measurements
      of SPFF. The knowledge generated from this study will benefit the food industry
      and breeding programs with the selection of sweetpotato varieties for improved
      SPFF quality.

PMID- 29178340
TI  - Spring-damper equivalents of the fractional, poroelastic, and poroviscoelastic
      models for elastography.
AB  - In MR elastography, it is common to use an elastic model for the tissue's
      response in order to interpret the results properly. More complex models, such as
      viscoelastic, fractional viscoelastic, poroelastic, or poroviscoelastic ones, are
      also used. These models appear at first sight to be very different, but here it
      is shown that they may all be expressed in terms of elementary viscoelastic
      models. For a medium expressed with fractional models, many elementary spring
      damper combinations are added, each of them weighted according to a long-tailed
      distribution of time constants or relaxation frequencies. This may open up a more
      physical interpretation of fractional models. The shear-wave component of the
      poroelastic model is shown to be modeled exactly by a three-component Zener
      model. The extended poroviscoelastic model is found to be equivalent to what is
      called a non-standard four-parameter model. Accordingly, the large number of
      parameters in the porous models can be reduced to the same number as in their
      viscoelastic equivalents. While the individual displacements from the solid and
      fluid parts cannot be measured individually, the main use of the
      poro(visco)elastic models is therefore as a physics-based method for determining
      parameters in a viscoelastic model.

PMID- 29178341
TI  - Persistence of contact allergy: a retrospective analysis.
AB  - BACKGROUND: Studies have shown that not all positive patch test reactions are
      reproducible upon retesting, that is, persistent. Non-persistent reactions might
      represent initial false-positive reactions, meaning that patients might
      unnecessarily avoid allergens. OBJECTIVES: To investigate the occurrence of both
      persistent and non-persistent patch test reactions, to explore possible
      explanations, and to investigate whether allergen-specific differences exist.
      METHODS: A retrospective analysis was performed on patients who were patch tested
      at least twice between 1 January 1995 and 31 October 2016, with at least one
      positive patch test reaction to an allergen that had been retested. Both
      univariable and multivariable analyses were performed to investigate the
      influence of several factors on persistence. RESULTS: Of 274 retested positive
      reactions in 119 patients, 183 (66.8%) reactions remained positive. The strongest
      predictor for non-persistence in both univariable and multivariable analyses was
      strength of the first patch test, with weak positive reactions being
      significantly less persistent. Regarding allergen groups, metals and fragrances
      were less persistent than other allergens. CONCLUSION: Weak positive reactions
      have a low persistence rate, and the dermatologist should be conservative in
      advising the patient on avoidance of these allergens, especially if clinical
      relevance is uncertain.

PMID- 29178342
TI  - MicroRNA-145 regulates disabled-2 and Wnt3a expression in cardiomyocytes under
      hyperglycaemia.
AB  - AIMS: MicroRNA-145 (miR-145) could protect cardiomyocyte apoptosis against
      oxidative stress and repair infarcted myocardium. Angiotensin II (Ang II), a pro
      inflammatory cytokine could modulate myocardial remodelling. However, the role of
      hyperglycaemia on miR-145 expression in cardiomyocyte or diabetes is not known.
      The effect of Ang II on miR-145 expression under hyperglycaemia in cardiomyocytes
      remains unknown. We sought to investigate the effect of hyperglycaemia and Ang II
      on miR-145 expression in cardiomyocytes. METHODS: Rat cardiomyocytes were
      cultured under high glucose concentration (25 mmol/L), and streptozotocin-induced
      diabetic rats were established. TaqMan(r) MicroRNA real-time quantitative assay
      was used to quantitate miR-145. RESULTS: Sustained high glucose concentration
      (hyperglycaemia) significantly decreased miR-145 expression in cardiomyocytes.
      Hyperglycaemia significantly increased Ang II mRNA expression and secretion from
      rat cardiomyocytes. Ang II suppressed miR-145 expression in cardiomyocytes.
      Hyperglycaemia increased Dab2 and decreased Wnt3a/beta-catenin expression in
      cardiomyocytes. Repression of miR-145 expression by Ang II resulted in increased
      Dab2 and decreased Wnt3a and beta-catenin expression under hyperglycaemia. In
      contrast, overexpression of miR-145 significantly decreased Dab2 mRNA and protein
      expression, whereas the mRNA and protein levels for Wnt3a and beta-catenin were
      significantly reduced in left ventricular myocardium from 5 days to 28 days in
      diabetic rats. The protein expression patterns of Dab2 and Wnt3a/beta-catenin in
      left ventricular myocardium of diabetic rats could be reversed upon treatment
      with valsartan. CONCLUSIONS: Ang II downregulates miR-145 to regulate Dab2 and
      Wnt3a/beta-catenin expression in cardiomyocytes under high glucose concentration.
      Ang II plays a critical role in the regulation of miR-145 in cardiomyocytes under
      hyperglycaemic conditions.

PMID- 29178344
TI  - Is the open cystectomy era over? An update on the available evidence.
AB  - In 2018, robot-assisted radical cystectomy will enter its 15th year. In an era
      where an effort is being made to standardize complication reporting and videos of
      the procedure are readily available, it is inevitable and justified that like
      everything novel, robot-assisted radical cystectomy should be scrutinized against
      the gold standard, open radical cystectomy. The present comparison is focused on
      several parameters: oncological, functional and complication outcomes, and direct
      and indirect costs. Meta-analysis and prospective randomized trials comparing
      robot-assisted radical cystectomy versus open radical cystectomy have been
      published, showing an oncological equivalence and in some cases an advantage of
      robot-assisted radical cystectomy in terms of postoperative morbidity. In the
      present review, we attempt to update the available knowledge on this debate and
      discuss the limitations of the current evidence that prevent us from drawing safe
      conclusions.

PMID- 29178343
TI  - PRDM14 directly interacts with heat shock proteins HSP90alpha and glucose
      regulated protein 78.
AB  - PRDM14 is overexpressed in various cancers and can regulate cancer phenotype
      under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic
      cancers has been reported to reduce cancer stem-like phenotypes, which are
      associated with aggressive tumor properties. Therefore, PRDM14 is considered a
      promising target for cancer therapy. To develop a pharmaceutical treatment, the
      mechanism and interacting partners of PRDM14 need to be clarified. Here, we
      identified the proteins interacting with PRDM14 in triple-negative breast cancer
      (TNBC) cells, which do not express the three most common types of receptor
      (estrogen receptors, progesterone receptors, and HER2). We obtained 13 candidates
      that were pulled down with PRDM14 in TNBC HCC1937 cells and identified them by
      mass spectrometry. Two candidates-glucose-regulated protein 78 (GRP78) and heat
      shock protein 90-alpha (HSP90alpha)-were confirmed in immunoprecipitation assay
      in two TNBC cell lines (HCC1937 and MDA-MB231). Surface plasmon resonance
      analysis using GST-PRDM14 showed that these two proteins directly interacted with
      PRDM14 and that the interactions required the C-terminal region of PRDM14, which
      includes zinc finger motifs. We also confirmed the interactions in living cells
      by NanoLuc luciferase-based bioluminescence resonance energy transfer (NanoBRET)
      assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased
      breast cancer stem-like CD24-  CD44+ and side population (SP) cells in HCC1937
      cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78
      inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation
      and SP cell number in HCC1937 cells. These results suggest that HSP90alpha and
      GRP78 interact with PRDM14 and participate in cancer regulation.

PMID- 29178345
TI  - Proton-Pump Inhibitor use and the risk of Ischaemic Stroke.

PMID- 29178346
TI  - Highlighting patterns of fungal diversity and composition shaped by ocean
      currents using the East China Sea as a model.
AB  - How ocean currents shape fungal transport, dispersal and more broadly fungal
      biogeography remains poorly understood. The East China Sea (ECS) is a complex and
      dynamic habitat with different water masses blending microbial communities. The
      internal transcribed spacer 2 region of fungal rDNA was analysed in water and
      sediment samples directly collected from the coastal (CWM), Kuroshio (KSWM),
      Taiwan warm (TWM) and the shelf mixed water mass (MWM), coupled with hydrographic
      properties measurements, to determine how ocean currents impact the fungal
      community composition. Almost 9k fungal operational taxonomic units (OTUs)
      spanning six phyla, 25 known classes, 102 orders and 694 genera were obtained.
      The typical terrestrial and freshwater fungal genus, Byssochlamys, was dominant
      in the CWM, while increasing abundance of a specific OTU affiliated with
      Aspergillus was revealed from coastal to open ocean water masses (TWM and KSWM).
      Compared with water samples, sediment harboured an increased diversity with
      distinct fungal communities. The proximity of the Yangtze and Qiantang estuaries
      homogenizes the surface water and sediment communities. A significant influence
      of ocean currents on community structure was found, which is believed to reduce
      proportionally the variation explained by environmental parameters at the scale
      of the total water masses. Dissolved oxygen and depth were identified as the
      major parameters structuring the fungal community. Our results indicate that
      passive fungal dispersal driven by ocean currents and river run-off, in
      conjunction with the distinct hydrographic conditions of individual water masses,
      shapes the fungal community composition and distribution pattern in the ECS.

PMID- 29178347
TI  - Tissuepatch is biocompatible and seals iatrogenic membrane defects in a rabbit
      model.
AB  - OBJECTIVE: To evaluate novel sealing techniques for their biocompatibility and
      sealing capacity of iatrogenic fetal membrane defects in a pregnant rabbit model.
      METHOD: At day 23 of gestation (term = d31), a standardized fetoscopy was
      performed through a 14G cannula. The resulting fetal membrane defect was closed
      with condensed collagen, collagen with fibrinogen, Tissuepatch, Duraseal, or a
      conventional collagen plug (Lyostypt) as reference. At d30, the fetuses were
      harvested and full thickness fetal membrane samples were analyzed. The study
      consisted of 2 consecutive parts: (1) biocompatibility testing by fetal survival,
      apoptosis, and infiltration of polymorphonuclear cells in the membranes and (2)
      the efficacy to seal fetal membrane defects. RESULTS: Three sealants (collagen
      with fibrinogen, Duraseal, or Lyostypt) were associated with a higher fetal
      mortality compared to control unmanipulated littermates and hence were excluded
      from further analysis. Tissuepatch was biocompatible, and amniotic fluid levels
      were comparable to those of control untouched littermates. Compared to the
      condensed collagen, Tissuepatch was also easier in surgical handling and induced
      limited cell proliferation. CONCLUSION: Tissuepatch had the best biocompatibility
      and efficacy in sealing an iatrogenic fetal membrane defect in the pregnant
      rabbit compared to other readily available sealants.

PMID- 29178348
TI  - Investigations into in situ Enterococcus faecalis biofilm removal by passive and
      active sodium hypochlorite irrigation delivered into the lateral canal of a
      simulated root canal model.
AB  - AIM: To investigate in situ Enterococcus faecalis biofilm removal from the
      lateral canal of a simulated root canal system using passive or active irrigation
      protocols. METHODOLOGY: Root canal models (n = 43) were manufactured from
      transparent resin materials using 3D printing. Each canal was created with an 18
      mm length, apical size 30, a .06 taper and a lateral canal of 3 mm length, with
      0.3 mm diameter. Biofilms were grown in the lateral canal and apical 3 mm of the
      main canal for 10 days. Three models from each group were examined for residual
      biofilm using SEM. The other forty models were divided into four groups (n = 10).
      The models were observed under a fluorescence microscope. Following 60 s of 9 mL
      of 2.5% NaOCl irrigation using syringe and needle, the irrigant was either left
      stagnant in the canal or activated using gutta-percha, sonic or ultrasonic
      methods for 30 s. Images were then captured every second using an external
      camera. The residual biofilm percentages were measured using image analysis
      software. The data were analysed using generalized linear mixed models. A
      significance level of 0.05 was used throughout. RESULTS: The greatest level of
      biofilm removal was obtained with ultrasonic agitation (66.76%) followed by sonic
      (45.49%), manual agitation (43.97%) and passive irrigation groups (38.67%),
      respectively. The differences were significant between the residual biofilm in
      the passive irrigation and both sonic and ultrasonic groups (P = 0.001).
      CONCLUSION: Agitation resulted in better penetration of 2.5% NaOCl into the
      lateral canal of an artificial root canal model. Ultrasonic agitation of NaOCl
      improved the removal of biofilm.

PMID- 29178349
TI  - Effect of body mass index on the incidence of perineal trauma.
AB  - OBJECTIVE: To investigate the association between perineal trauma at childbirth
      and maternal body mass index (BMI), and estimate the risk of perineal trauma
      among different BMI groups. METHODS: Data were retrospectively assessed from all
      vaginal deliveries in a UK tertiary maternity unit between 1999 and 2014.
      Associations between BMI at booking and first- and second-degree tears (minor
      perineal trauma), third- and fourth-degree tears (obstetric anal sphincter
      injuries [OASIS]), and frequency of instrumental deliveries were assessed.
      Multivariate logistic regression included the factors BMI (weight in kilograms
      divided by the square of height in meters), age, ethnicity, smoking, parity,
      pregnancy length, episiotomies, instrumental delivery, and birth weight. RESULTS:
      Data from 45 557 deliveries were used. Compared with women with a normal BMI
      (<25), odds of minor perineal trauma were significantly reduced among women with
      obesity (BMI 30 to <35; odds ratio [OR] 0.91, 95% confidence interval [CI] 0.84
      0.99) or severe obesity (BMI >=35; OR 0.87, 95% CI 0.77-0.98). OASIS was not
      significantly associated with BMI. Instrumental delivery rates were higher among
      women with normal BMI (5936/27 107; 22.0%) than among those with severe obesity
      (284/2032; 14.0%). CONCLUSION: Increased BMI at booking was associated with a
      reduced incidence of minor perineal trauma at delivery, but was not associated
      with OASIS.

PMID- 29178350
TI  - Assessment of prescribing practices at the primary healthcare facilities in
      Botswana with an emphasis on antibiotics: Findings and implications.
AB  - BACKGROUND AND AIMS: Inappropriate drug prescribing has increased especially in
      developing countries where systems for monitoring medicine use are not well
      developed. This increases the rate of antimicrobial resistance. The study aim was
      to assess the prescribing patterns among urban primary health facilities in
      Botswana to provide future guidance including developing future quality
      indicators. METHODS: Retrospective data from patients' records between January
      and December 2013 in 19 clinics were collected in a cross-sectional study. The
      WHO/International Network for Rational Use of Drugs indicators were used to
      assess prescribing patterns in the study clinics. RESULTS: Average number of
      drugs per prescription was 2.8; 78.6% of the prescribed antibiotics were by
      International Non-proprietary Name and 96.1% complied with the Botswana Essential
      Drugs List. Overall rate of antibiotic prescribing was high (42.7%) with 14.7%,
      5.9% and 1.3% of prescriptions having two, three and four antibiotics,
      respectively. Systemic antibiotics (JO1C) accounted for 45.4% of prescribed
      antibiotics of which amoxicillin accounted for 28.4% and metronidazole 14.4% of
      all antibiotic prescriptions. There was low use of co-amoxiclav (0.3% of all
      antibiotic prescriptions). Third generation cephalosporins and macrolides
      accounted for 9.8% and 6.2% of antibiotic prescriptions respectively, with no
      prescribing of fluoroquinolones. The majority of indications (87%) for antibiotic
      prescriptions were according to ICD classification. CONCLUSIONS: While most
      indications for antibiotic prescriptions were based on signs and symptoms
      according to ICD, antibiotic prescribing rates were high with some conditions not
      requiring antibiotics because they are viral infections. There is a need to
      further improve prescribing practices through induction and training of in
      service prescribers. An effective management tool for monitoring antibiotic
      prescribing practices at Primary Health Care facilities should be designed and
      implemented, including developing robust quality indicators.

PMID- 29178351
TI  - Printing Semiconductor-Insulator Polymer Bilayers for High-Performance Coplanar
      Field-Effect Transistors.
AB  - Source-semiconductor-drain coplanar transistors with an organic semiconductor
      layer located within the same plane of source/drain electrodes are attractive for
      next-generation electronics, because they could be used to reduce material
      consumption, minimize parasitic leakage current, avoid cross-talk among different
      devices, and simplify the fabrication process of circuits. Here, a one-step, drop
      casting-like printing method to realize a coplanar transistor using a model
      semiconductor/insulator [poly(3-hexylthiophene) (P3HT)/polystyrene (PS)] blend is
      developed. By manipulating the solution dewetting dynamics on the metal electrode
      and SiO2 dielectric, the solution within the channel region is selectively
      confined, and thus make the top surface of source/drain electrodes completely
      free of polymers. Subsequently, during solvent evaporation, vertical phase
      separation between P3HT and PS leads to a semiconductor-insulator bilayer
      structure, contributing to an improved transistor performance. Moreover, this
      coplanar transistor with semiconductor-insulator bilayer structure is an ideal
      system for injecting charges into the insulator via gate-stress, and the thus
      formed PS electret layer acts as a "nonuniform floating gate" to tune the
      threshold voltage and effective mobility of the transistors. Effective field
      effect mobility higher than 1 cm2 V-1 s-1 with an on/off ratio > 107 is realized,
      and the performances are comparable to those of commercial amorphous silicon
      transistors. This coplanar transistor simplifies the fabrication process of
      corresponding circuits.

PMID- 29178352
TI  - Concise Review: The Use of Stem Cells for Understanding and Treating Huntington's
      Disease.
AB  - Two decades ago, researchers identified that a CAG expansion mutation in the
      huntingtin (HTT) gene was involved in the pathogenesis of Huntington's disease
      (HD). However, since the identification of the HTT gene, there has been no
      advance in the development of therapeutic strategies to prevent or reduce the
      progression of HD. With the recent advances in stem cell biology and human cell
      reprogramming technologies, several novel and exciting pathways have emerged
      allowing researchers to enhance their understanding of the pathogenesis of HD, to
      identify and screen potential drug targets, and to explore alternative donor cell
      sources for cell replacement therapy. This review will discuss the role of
      compensatory neurogenesis in the HD brain, the use of stem cell-based therapies
      for HD to replace or prevent cell loss, and the recent advance of cell
      reprogramming to model and/or treat HD. These new technologies, coupled with
      advances in genome editing herald a promising new era for HD research with the
      potential to identify a therapeutic strategy to alleviate this debilitating
      disorder. Stem Cells 2018;36:146-160.

PMID- 29178353
TI  - The risk of febrile neutropenia in breast cancer patients following adjuvant
      chemotherapy is predicted by the time course of interleukin-6 and C-reactive
      protein by modelling.
AB  - AIMS: Early identification of patients with febrile neutropenia (FN) is desirable
      for initiation of preventive treatment, such as with antibiotics. In this study,
      the time courses of two inflammation biomarkers, interleukin (IL)-6 and C
      reactive protein (CRP), following adjuvant chemotherapy of breast cancer, were
      characterized. The potential to predict development of FN by IL-6 and CRP, and
      other model-derived and clinical variables, was explored. METHODS: The IL-6 and
      CRP time courses in cycles 1 and 4 of breast cancer treatment were described by
      turnover models where the probability for an elevated production following
      initiation of chemotherapy was estimated. Parametric time-to-event models were
      developed to describe FN occurrence to assess: (i) predictors available before
      chemotherapy is initiated; (ii) predictors available before FN occurs; and (iii)
      predictors available when FN occurs. RESULTS: The IL-6 and CRP time courses were
      successfully characterized with peak IL-6 typically occurring 2 days prior to CRP
      peak. Of all evaluated variables the CRP time course was most closely associated
      with the occurrence of FN. Since the CRP peak typically occurred at the time of
      FN diagnosis it will, however, have limited value for identifying the need for
      preventive treatment. The time course of IL-6 was the predictor that could best
      forecast FN events. Of the variables available at baseline, age was the best,
      although in comparison a relatively weak, predictor. CONCLUSIONS: The developed
      models add quantitative knowledge about IL-6 and CRP and their relationship to
      the development of FN. The study suggests that IL-6 may have potential as a
      clinical predictor of FN if monitored during myelosuppressive chemotherapy.

PMID- 29178355
TI  - Hierarchical Hollow Nanoprisms Based on Ultrathin Ni-Fe Layered Double Hydroxide
      Nanosheets with Enhanced Electrocatalytic Activity towards Oxygen Evolution.
AB  - The oxygen evolution reaction (OER) is involved in various renewable energy
      systems, such as water-splitting cells and metal-air batteries. Ni-Fe layered
      double hydroxides (LDHs) have been reported as promising OER electrocatalysts in
      alkaline electrolytes. The rational design of advanced nanostructures for Ni-Fe
      LDHs is highly desirable to optimize their electrocatalytic performance. Herein,
      we report a facile self-templated strategy for the synthesis of novel
      hierarchical hollow nanoprisms composed of ultrathin Ni-Fe LDH nanosheets.
      Tetragonal nanoprisms of nickel precursors were first synthesized as the self
      sacrificing template. Afterwards, these Ni precursors were consumed during the
      hydrolysis of iron(II) sulfate for the simultaneous growth of a layer of Ni-Fe
      LDH nanosheets on the surface. The resultant Ni-Fe LDH hollow prisms with large
      surface areas manifest high electrocatalytic activity towards the OER with low
      overpotential, small Tafel slope, and remarkable stability.

PMID- 29178354
TI  - Hyperexcitability of the network contributes to synchronization processes in the
      human epileptic neocortex.
AB  - KEY POINTS: Hyperexcitability and hypersynchrony of neuronal networks are thought
      to be linked to the generation of epileptic activity in both humans and animal
      models. Here we show that human epileptic postoperative neocortical tissue is
      able to generate two different types of synchronies in vitro. Epileptiform bursts
      occurred only in slices derived from epileptic patients and were hypersynchronous
      events characterized by high levels of excitability. Spontaneous population
      activity emerged in both epileptic and non-epileptic tissue, with a significantly
      lower degree of excitability and synchrony, and could not be linked to epilepsy.
      These results help us to understand better the role of excitatory and inhibitory
      neuronal circuits in the generation of population events, and to define the
      subtle border between physiological and pathological synchronies. ABSTRACT:
      Interictal activity is a hallmark of epilepsy diagnostics and is linked to
      neuronal hypersynchrony. Little is known about perturbations in human epileptic
      neocortical microcircuits, and their role in generating pathological synchronies.
      To explore hyperexcitability of the human epileptic network, and its contribution
      to convulsive activity, we investigated an in vitro model of synchronous burst
      activity spontaneously occurring in postoperative tissue slices derived from
      patients with or without preoperative clinical and electrographic manifestations
      of epileptic activity. Human neocortical slices generated two types of
      synchronies. Interictal-like discharges (classified as epileptiform events)
      emerged only in epileptic samples, and were hypersynchronous bursts characterized
      by considerably elevated levels of excitation. Synchronous population activity
      was initiated in both epileptic and non-epileptic tissue, with a significantly
      lower degree of excitability and synchrony, and could not be linked to epilepsy.
      However, in pharmacoresistant epileptic tissue, a higher percentage of slices
      exhibited population activity, with higher local field potential gradient
      amplitudes. More intracellularly recorded neurons received depolarizing synaptic
      potentials, discharging more reliably during the events. Light and electron
      microscopic examinations showed slightly lower neuron densities and higher
      densities of excitatory synapses in the human epileptic neocortex. Our data
      suggest that human neocortical microcircuits retain their functionality and
      plasticity in vitro, and can generate two significantly different synchronies. We
      propose that population bursts might not be pathological events while interictal
      like discharges may reflect the epileptogenicity of the human cortex. Our results
      show that hyperexcitability characterizes the human epileptic neocortical
      network, and that it is closely related to the emergence of synchronies.

PMID- 29178356
TI  - Effects of observing normal and abnormal goal-directed hand movements on
      somatosensory cortical activation.
AB  - Existing evidence indicates the importance of observing correct, normal actions
      on the motor cortical activities. However, the exact neurophysiological
      mechanisms, particularly in the somatosensory system, remain unclear. This study
      aimed to elucidate the effects of observing normal and abnormal hand movements on
      the contralateral primary somatosensory (cSI), contralateral (cSII) and
      ipsilateral (iSII) secondary somatosensory activities. Experiment I was designed
      to investigate the effects of motor outputs on the somatosensory processing, in
      which subjects were instructed to relax or manipulate a small cube. Experiment II
      was tailored to examine the somatosensory responses to the observation of normal
      (Normal) and abnormal (Abnormal) hand movements. The subjects received electrical
      stimulation to right median nerve and magnetoencephalography (MEG) recordings
      during the whole experimental period. Regional cortical activation and functional
      connectivity were analyzed. Compared to the resting condition, a reduction in cSI
      and an enhancement of SII activation was found when subjects manipulated a cube,
      suggesting the motor outputs have an influence on the somatosensory responses.
      Further investigation of the effects of observing different hand movements showed
      that cSII activity was significantly stronger in the Normal than Abnormal
      condition. Moreover, compared with Abnormal condition, a higher cortical
      coherence of cSI-iSII at theta bands and cSII-iSII at beta bands was found in
      Normal condition. Conclusively, the present results suggest stronger activation
      and enhanced functional connectivity within the somatosensory system during the
      observation of normal than abnormal hand movements. These findings also highlight
      the importance of viewing normal, correct hands movements in the stroke
      rehabilitation.

PMID- 29178357
TI  - Synthesis and chromatographic evaluation of phenyl/tetrazole bonded stationary
      phase based on thiol-epoxy ring opening reaction.
AB  - A silica-based reversed-phase stationary phase bonding with phenyl and tetrazole
      groups was synthesized by thiol-epoxy ring opening reaction. The bonded groups
      could not only provide hydrophobic interaction, but also pi-pi, hydrogen bonding,
      electrostatic interactions, and so on. The results of characterization with
      elemental analysis and solid-state 13 C cross-polarization magic-angle-spinning
      NMR spectroscopy indicated the successful preparation of phenyl/tetrazole
      sulfoether bonded stationary phase. Chromatographic evaluation revealed that
      phenyl/tetrazole sulfoether bonded stationary phase behaved well under the
      reversed-phase mode. The column parameters (H, S*, A, B, and C) showed different
      selectivity compared with some typical commercial columns, and it was validated
      by the separation of estrogen, ginsenoside, alkaloid samples. Based on the
      different selectivity between phenyl/tetrazole sulfoether bonded stationary phase
      and C18 columns, phenyl/tetrazole sulfoether bonded stationary phase also showed
      potential to construct a 2D reversed-phase liquid chromatography system with C18.
      And it was verified by the separation of corydalis tuber and curcuma zedoary
      extracts.

PMID- 29178358
TI  - Conventional-SCS vs. Burst-SCS and the Behavioral Effect on Mechanical
      Hypersensitivity in a Rat Model of Chronic Neuropathic Pain: Effect of Amplitude.
AB  - OBJECTIVE: Various spinal cord stimulation (SCS) modes are used in the treatment
      of chronic neuropathic pain disorders. Conventional (Con) and Burst-SCS are
      hypothesized to exert analgesic effects through different stimulation-induced
      mechanisms. Preclinical electrophysiological findings suggest that stimulation
      intensity is correlated with the effectiveness of Burst-SCS. Therefore, we aimed
      to investigate the relation between amplitude (charge per second) and behavioral
      effects in a rat model of chronic neuropathic pain, for both Conventional Spinal
      Cord Stimulation (Con-SCS) and biphasic Burst-SCS. MATERIALS AND METHODS: Animals
      (n = 12 rats) received a unilateral partial sciatic nerve ligation, after which
      they were implanted with quadripolar electrodes in the epidural space at thoracic
      level 13. Mechanical hypersensitivity was assessed using paw withdrawal
      thresholds (WTs) to von Frey monofilaments, at various SCS intensities
      (amplitudes) and multiple time points during 60 minutes of stimulation and 30
      minutes post stimulation. RESULTS: Increasing amplitude was shown to improve the
      efficacy of Con-SCS, whereas the efficacy of Burst-SCS showed a non-monotonic
      relation with amplitude. Con-SCS at 66% MT (n = 5) and Burst-SCS at 50% MT (n =
      6) were found to be equally effective in normalizing mechanical hypersensitivity.
      However, in the assessed time period Burst-SCS required significantly more mean
      charge per second to do so (p < 0.01). When applied at comparable mean charge per
      second, Con-SCS resulted in a superior behavioral outcome (p < 0.01), compared
      with Burst-SCS. CONCLUSION: Biphasic Burst-SCS requires significantly more mean
      charge per second in order to achieve similar pain relief, as compared with Con
      SCS, in an experimental model of chronic neuropathic pain.

PMID- 29178360
TI  - Multifactorial disease risk calculator: Risk prediction for multifactorial
      disease pedigrees.
AB  - Construction of multifactorial disease models from epidemiological findings and
      their application to disease pedigrees for risk prediction is nontrivial for all
      but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool
      facilitating this. It provides a user-friendly interface, extending a reported
      methodology based on a liability-threshold model. Multifactorial disease models
      incorporating all the following features in combination are handled: quantitative
      risk factors (including polygenic scores), categorical risk factors (including
      major genetic risk loci), stratified age of onset curves, and the partition of
      the population variance in disease liability into genetic, shared, and unique
      environment effects. It allows the application of such models to disease
      pedigrees. Pedigree-related outputs are (i) individual disease risk for pedigree
      members, (ii) n year risk for unaffected pedigree members, and (iii) the disease
      pedigree's joint liability distribution. Risk prediction for each pedigree member
      is based on using the constructed disease model to appropriately weigh evidence
      on disease risk available from personal attributes and family history. Evidence
      is used to construct the disease pedigree's joint liability distribution. From
      this, lifetime and n year risk can be predicted. Example disease models and
      pedigrees are provided at the website and are used in accompanying tutorials to
      illustrate the features available. The website is built on an R package which
      provides the functionality for pedigree validation, disease model construction,
      and risk prediction. Website: http://grass.cgs.hku.hk:3838/mdrc/current.

PMID- 29178359
TI  - Elevated luteinizing hormone despite normal testosterone levels in older men
      natural history, risk factors and clinical features.
AB  - OBJECTIVE: Elevated luteinizing hormone (LH) with normal testosterone (T)
      suggests compensated dysregulation of the gonadal axis. We describe the natural
      history, risk factors and clinical parameters associated with the development of
      high LH (HLH, LH >9.4 U/L) in ageing men with normal T (T >= 10.5 nmol/L).
      DESIGN, PATIENTS AND MEASUREMENTS: We conducted a 4.3-year prospective
      observational study of 3369 community-dwelling European men aged 40-79 years.
      Participants were classified as follows: incident (i) HLH (n = 101, 5.2%);
      persistent (p) HLH (n = 128, 6.6%); reverted (r) HLH (n = 46, 2.4%); or
      persistent normal LH (pNLH, n = 1667, 85.8%). Potential predictors and changes in
      clinical features associated with iHLH and rHLH were analysed using regression
      models. RESULTS: Age >70 years (OR = 4.12 [2.07-8.20]), diabetes (OR = 2.86 [1.42
      5.77]), chronic pain (OR = 2.53 [1.34-4.77]), predegree education (OR = 1.79
      [1.01-3.20]) and low physical activity (PASE <= 78, OR = 2.37 [1.24-4.50])
      predicted development of HLH. Younger age (40-49 years, OR = 8.14 [1.35-49.13])
      and nonsmoking (OR = 5.39 [1.48-19.65]) predicted recovery from HLH. Men with
      iHLH developed erectile dysfunction, poor health, cardiovascular disease (CVD)
      and cancer more frequently than pNLH men. In pHLH men, comorbidities, including
      CVD, developed more frequently, and cognitive and physical function deteriorated
      more, than in pNLH men. Men with HLH developed primary hypogonadism more
      frequently (OR = 15.97 [5.85-43.60]) than NLH men. Men with rHLH experienced a
      small rise in BMI. CONCLUSIONS: Elevation of LH with normal T is predicted by
      multiple factors, reverts frequently and is not associated with unequivocal
      evidence of androgen deficiency. High LH is a biomarker for deteriorating health
      in aged men who tend to develop primary hypogonadism.

PMID- 29178361
TI  - Outcome of patients with relapsed/refractory acute lymphoblastic leukemia after
      blinatumomab failure: No change in the level of CD19 expression.
AB  - Blinatumomab, a bi-specific T-cell engaging CD3-CD19 antibody construct, has
      shown significant activity in patients with relapsed/refractory (R/R) B-cell
      acute lymphoblastic leukemia (ALL). Despite this improvement, most patients
      relapse. Here, we describe the outcome of 68 patients with R/R ALL after failure
      of blinatumomab therapy: 38 (56%) blinatumomab refractory; 30 (44%) relapsing
      after initial response. After a median follow-up of 49 months, 9 (13%) patients
      remained alive. The median overall survival after blinatumomab failure was 5.2
      months. At the time of failure, among 61 patients evaluated for immunophenotype,
      56 (92%) had CD19-positive blasts; only five (8%) had ALL recurrence with CD19
      negative disease. Two patients progressed with lower CD19 expression. In summary,
      the outcome of patients with R/R ALL after blinatumomab failure is poor and
      treatment of these patients remains an unmet medical need. Our findings indicate
      that blinatumomab therapy would not exclude a significant number of patients from
      the potential benefit of subsequent CD19-directed therapies such as chimeric
      antigen receptor T-cell therapy.

PMID- 29178362
TI  - The relationship between 18 F-FDG-PETCT-derived markers of tumour metabolism and
      systemic inflammation in patients with recurrent disease following surgery for
      colorectal cancer.
AB  - AIM: 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18
      F-FDG-PETCT)-derived markers of tumour metabolism have been reported to have
      prognostic significance in a variety of tumours. Host inflammation is also
      recognized to have prognostic significance. The aim of the present study was to
      investigate the relationship between these markers and host systemic inflammation
      in patients undergoing elective surgery for colorectal cancer. METHOD: Patients
      with histologically confirmed colorectal cancer who underwent elective surgery
      between 2008 and 2015 and also underwent 18 F-FDG-PETCT at a single centre were
      included (n = 103). The neutrophil-lymphocyte ratio (NLR) and modified Glasgow
      Prognostic Score (mGPS) were derived from routine blood tests. The maximum
      standardized uptake (SUVmax), peak standardized uptake (SUVpeak), metabolic
      tumour volume (MTV) and total lesion glycolysis (TLG) were measured. RESULTS:
      There was no association between 18 F-FDG-PETCT measures of tumour metabolism and
      systemic inflammation in the 33 patients who underwent preoperative imaging. Of
      the 70 patients with recurrent disease who underwent 18 F-FDG-PETCT during follow
      up, patients with NLR >= 5 had a significantly higher SUVmax (20 vs 7, P =
      0.002), SUVpeak (14 vs 5, P < 0.001), MTV (29 g vs 2 g, P = 0.001) and TLG (338 g
      vs 9 g, P < 0.001). Similarly, patients with a mGPS of 1-2 at the time of 18 F
      FDG-PETCT had a significantly higher median SUVmax (11 vs 6, P = 0.048), SUVpeak
      (8 vs 4, P = 0.046), MTV (13 ml vs 2 ml, P = 0.005) and TLG (146 g vs 10 g, P =
      0.004). CONCLUSION: The present study reports a direct association between 18 F
      FDG-PETCT-derived measures of tumour metabolism and systemic inflammation in
      patients with recurrent colorectal cancer.

PMID- 29178363
TI  - Interventions to promote healthy eating choices when dining out: A systematic
      review of reviews.
AB  - PURPOSE: To synthesize review research pertaining to the effectiveness of
      interventions in dining-out settings to reduce food/calorie consumption. METHODS:
      A rapid review methodology was employed to focus on synthesized research. A
      comprehensive search for peer-reviewed systematic reviews from 2010 to 2015
      yielded 1,847 citations. Following screening, ten systematic reviews were
      included. RESULTS: The 10 included systematic reviews identified 183 primary
      studies evaluating evidence in three behavioural intervention areas: social
      models/norms, manipulation of size, and provision of health information. Three
      systematic reviews evaluating the use of social models/norms found this was an
      effective intervention for influencing food intake. Five systematic reviews that
      assessed manipulation of portion/dishware/cutlery size found a small-to-moderate
      effect on food consumption. Three systematic reviews looked at the provision of
      health information, which was not effective alone; however, in combination with
      contextual or interpretive material such as traffic lights or exercise
      equivalence, this was shown to reduce calorie consumption. One systematic review
      covered two topic areas. CONCLUSIONS: The results indicate that policies or
      interventions that aim to improve healthy choices or consumption when dining out
      would benefit from harnessing social norms and positive positioning of social
      identity. Furthermore, provision of health information should always be
      accompanied by an interpretative guide, such as traffic lights. Manipulation of
      plate/portion/cutlery size may be effective; however, the effect size is small
      and further research is required to investigate whether this effect is retained
      in overweight or obese populations. Statement of contribution What is already
      known on this subject? Eating behaviours (food choices, consumption) have played
      a role in the obesity epidemic. Behavioural 'nudges' have tried to increase
      healthier eating choices. What does this study add? Social norms and modelling
      have a strong influence in both directions on how much people consume. Provision
      of nutritional information needs to be paired with interpretative aids (e.g.,
      traffic lights). Manipulation of portion size is less effective in overweight
      populations.

PMID- 29178364
TI  - Fine-needle aspiration cytology for parotid lesions, can we avoid surgery?
AB  - OBJECTIVE: Salivary gland neoplasms are rare tumours, with most arising in the
      parotid gland. Fine-needle aspiration cytology (FNAC) is a common method for
      preoperative evaluation of parotid masses, although its usefulness is
      controversial. This study was designed to evaluate the accuracy of FNAC in a
      large cohort of patients, with emphasis on diagnosis of benign tumours and
      especially Warthin tumour which can be managed conservatively. STUDY DESIGN:
      Retrospective case series with chart review. SETTING: Tertiary medical centre.
      SUBJECTS AND METHODS: From 1991 to 2014, all patients 18 or older with both
      preoperative FNAC and postoperative pathology report were included. Patients with
      a history of head and neck malignancy or chronic sialoadenitis and patients who
      had undergone prior oncological treatment were excluded. RESULTS: 470 patients
      were available for analysis. Overall accuracy was 82.6%. Positive predictive
      value (PPV) varied between 88.6% and 94.3% for pleomorphic adenoma and 77.1%-100%
      for Warthin tumour, with values varying depending on different characteristics of
      patients (eg age, smoking status). For pathologically proven malignant tumours,
      the FNAC diagnosis was benign or non-diagnostic in 26% of the cases. CONCLUSION:
      Fine-needle aspiration cytology has limited utility in confirming a benign
      diagnosis of a parotid mass for most patients, although for some subpopulations,
      the PPV may be high enough to defer surgery.

PMID- 29178365
TI  - Levodopa: A new look at an old friend.
AB  - Levodopa is the most effective antiparkinsonian agent, but chronic treatment is
      associated with the development of motor complications in the majority of
      patients with PD. Recent scientific and clinical advances are improving this
      situation. Long-term, double-blind studies demonstrate that dose is an important
      risk factor for the development of both motor fluctuations and dyskinesia, and
      suggest that it is best to use low doses of l-dopa when possible. Inhaled l-dopa
      and sublingual apomorphine are now being developed as rescue therapies that
      permit rapid and predictable reversal of off periods. Finally, substantial
      evidence suggests that motor complications are related to the nonphysiological
      restoration of brain dopamine with intermittent oral doses of standard l-dopa.
      Double-blind studies demonstrate significant clinical benefits with continuous
      intraintestinal infusion of l-dopa. New approaches that provide continuous plasma
      l-dopa levels without the need for a surgical procedure are currently being
      investigated. Finally, the development of an oral long-acting form of l-dopa that
      provides continuous plasma l-dopa levels is actively being pursued. Collectively,
      these approaches offer the potential to considerably reduce and even prevent the
      disability associated with l-dopa-induced motor complications. (c) 2017
      International Parkinson and Movement Disorder Society.

PMID- 29178366
TI  - Do we overestimate left ventricular ejection fraction by two-dimensional
      echocardiography in patients with left bundle branch block?
AB  - AIMS: Left bundle branch block (LBBB) causes a dyssynchronized contraction of
      left ventricle. This is a kind of regional wall-motion abnormality and measuring
      left ventricular ejection fraction (LVEF) by two-dimensional (2D)
      echocardiography could be less reliable in this particular condition. Our aim was
      to evaluate the role of dyssynchrony index (SDI), measured by three-dimensional
      (3D) echocardiography, in assessment of LVEF and left ventricular volumes
      accurately in patients with LBBB. METHODS AND RESULTS: In this case-control
      study, we included 52 of 64 enrolled participants (twelve participants with poor
      image quality were excluded) with LBBB and normal LVEF or nonischemic
      cardiomyopathy. Left ventricular ejection fraction (LVEF) and left ventricular
      volumes were assessed by 2D (modified Simpson's rule) and 3D (four beats full
      volume analysis) echocardiography and the impact of SDI on results were
      evaluated. In patients with SDI >=6%, LVEF measurements were significantly
      different (46.00% [29.50-52.50] vs 37.60% [24.70-45.15], P < .001) between 2D and
      3D echocardiography, respectively. In patients with SDI < 6%, there were no
      significant differences between two modalities in terms of LVEF measurements
      (54.50% [49.00-59.00] vs 54.25% [40.00-58.25], P = .193). LV diastolic volumes
      were not significantly different while systolic volumes were underestimated by 2D
      echocardiography, and this finding was more pronounced when SDI >= 6%.
      CONCLUSION: In patients with LBBB and high SDI (>=6%), LVEF values were
      overestimated and systolic volumes were underestimated by 2D echocardiography
      compared to 3D echocardiography.

PMID- 29178367
TI  - Estimation of discrete survival function for error-prone diagnostic tests.
AB  - The product limit or Kaplan-Meier (KM) estimator is commonly used to estimate the
      survival function in the presence of incomplete time to event. Application of
      this method assumes inherently that the occurrence of an event is known with
      certainty. However, the clinical diagnosis of an event is often subject to
      misclassification due to assay error or adjudication error, by which the event is
      assessed with some uncertainty. In the presence of such errors, the true
      distribution of the time to first event would not be estimated accurately using
      the KM method. We develop a method to estimate the true survival distribution by
      incorporating negative predictive values and positive predictive values, into a
      KM-like method of estimation. This allows us to quantify the bias in the KM
      survival estimates due to the presence of misclassified events in the observed
      data. We present an unbiased estimator of the true survival function and its
      variance. Asymptotic properties of the proposed estimators are provided, and
      these properties are examined through simulations. We demonstrate our methods
      using data from the Viral Resistance to Antiviral Therapy of Hepatitis C study.

PMID- 29178368
TI  - Mammographic density and associated predictive factors for Chinese women.

PMID- 29178369
TI  - Pharmacokinetics and tissue distribution of pefloxacin mesylate in chickens.
AB  - A specific, sensitive and stable high-performance liquid chromatography (HPLC)
      based analytical method was established to determine the level of pefloxacin
      mesylate (PM) in the plasma and various tissues of chickens. Chickens were
      randomly assigned to 12 equal experiment groups, including 11 treatment groups
      and one control group. The chickens in the treatment groups received oral
      administration of PM and were sacrificed at different pre-determined time points,
      with their blood and various organs harvested, extracted and analyzed by HPLC to
      quantify the level of the residual antibiotic. Method validation studies
      indicated that the HPLC measurement showed excellent precision, reproducibility,
      stability and robustness. The obtained pharmacokinetic parameters suggested that
      PM reached peak levels in various tissues within 1-2 h after its oral
      administration, and was mainly concentrated in liver and kidney. The antibiotic
      was also found to be cleared from chicken crureus, brain, testes, ovaries and
      pancreas at higher rates compared with other organs. Overall, the rapid
      accumulation of PM could at least be partially attributed to its relatively slow
      organ clearance. These results could serve as a useful guidance for the rational
      use of PM and other quinolone-derived antimicrobials in the treatment of
      infectious diseases in chickens and other animals.

PMID- 29178370
TI  - Use and perceptions of plastination among medical anatomy educators in the United
      States.
AB  - Traditionally, medical schools have maintained collections of tissues/organs to
      engage students in anatomy. Such collections are often stored in volatile and
      toxic preservatives. Plastination is an alternative tissue preservation technique
      in which polymers replace water and lipids resulting in benign, dry, and
      anatomically authentic specimens. Plastination is used in medical education
      internationally; however, its use within U.S. medical schools is not widely
      discussed in the anatomical literature. This study aimed to determine the
      knowledge, use, and perceptions of plastination as a teaching tool among U.S.
      anatomy medical educators. A total of 98 medical anatomy educators who fit
      inclusion criteria and teach allopathic (MD) students and/or osteopathic (DO)
      students in the United States completed a national survey, representing 77
      medical schools across 37 states. Of these, 100% had heard of plastination, 57%
      correctly defined plastination, but only 39% currently utilize plastinates for
      anatomy education. The most frequent explanation for nonuse of plastinates was a
      preference for the dissection experience, followed by lack of resources and
      negative past experiences related to durability and quality. A majority (75%) of
      U.S. medical anatomy educators perceived plastination as a good supplement to,
      but not a replacement for, cadaveric dissection, 19% indicated no curiosity to
      use plastination or considered it not useful, and 14% expressed ethical concerns.
      These findings suggest plastinates are more widely used in the United States than
      reflected by the literature; however, perceptions regarding their utility
      indicate a dominant theme for their use to supplement, not replace, cadaveric
      dissection. Clin. Anat, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178371
TI  - Insulin degludec overdose may lead to long-lasting hypoglycaemia through its
      markedly prolonged half-life.
AB  - BACKGROUND: Overdose of insulin often causes long-lasting severe hypoglycaemia.
      Insulin degludec has the longest duration of action among the available insulin
      products; thus, an overdose of insulin degludec can lead to long-lasting
      hypoglycaemia. In the present paper, we report the case of a woman with long
      lasting hypoglycaemia attributable to insulin degludec overdose and markedly
      prolonged insulin degludec half-life. CASE REPORT: A 64-year-old woman with Type
      2 diabetes receiving insulin therapy was taken to an emergency department because
      of disturbed consciousness 21 h after self-injection of 300 units of insulin
      degludec (4.34 units/kg). Her plasma glucose level was 2.3 mmol/l. She received
      repeated intravenous boluses of dextrose for 43 h with continuous intravenous
      dextrose infusion, but no improvement in long-lasting hypoglycaemia or
      consciousness was observed. Considering the possibility of adrenal insufficiency,
      intravenous dexamethasone was administered, and her plasma glucose levels
      subsequently remained above 5.5 mmol/l without intravenous dextrose boluses. She
      gradually regained consciousness. A total of 34 h after the overdose, her plasma
      immunoreactive insulin levels were markedly increased and then gradually declined
      over ~400 h. The insulin degludec half-life was 40.76 h. CONCLUSION: Although the
      reported half-life of insulin degludec in the body is ~25 h when administered in
      standard doses (0.4-0.8 units/kg), no study has investigated its half-life after
      overdose. In the present case, the half-life of insulin degludec was ~1.6 times
      longer than that observed with standard doses, probably leading to long-lasting
      hypoglycaemia. Physicians should be aware of the possibility of unexpected long
      lasting severe hypoglycaemia resulting from insulin degludec overdose.

PMID- 29178372
TI  - THC alters alters morphology of neurons in medial prefrontal cortex, orbital
      prefrontal cortex, and nucleus accumbens and alters the ability of later
      experience to promote structural plasticity.
AB  - Psychoactive drugs have the ability to alter the morphology of neuronal dendrites
      and spines and to influence later experience-dependent structural plasticity. If
      rats are given repeated injections of psychomotor stimulants (amphetamine,
      cocaine, nicotine) prior to being placed in complex environments, the drug
      experience interferes with the ability of the environment to increase dendritic
      arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol
      (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and
      nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants
      will also interfere with later experience-dependent structural plasticity we gave
      Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in
      complex environments or standard laboratory caging for 90 days. Brains were
      subsequently processed for Golgi-Cox staining and analysis of dendritic
      morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC
      altered both dendritic arborization and spine density in all three regions, and,
      like psychomotor stimulants, THC influenced the effect of later experience in
      complex environments to shape the structure of neurons in these three regions. We
      conclude that THC may therefore contribute to persistent behavioral and cognitive
      deficits associated with prolonged use of the drug.

PMID- 29178373
TI  - Geographic impact evaluation of the quality of Alismatis Rhizoma by untargeted
      metabolomics and quantitative assay.
AB  - The geographic impact on the quality of Alismatis Rhizoma (derived from the tuber
      of Alisma orientale), a reputable diuretic traditional Chinese medicine, has
      seldom been evaluated. Here a metabolomics-driven approach targeting the
      bioactive protostane triterpenes was developed, by incorporating UHPLC with
      quadrupole time-of-flight mass spectrometry-based untargeted metabolite profiling
      and multiple reaction monitoring quantitative assay, to probe the triterpene
      differences between Alismatis Rhizoma samples collected from Sichuan, Fujian, and
      Jiangxi Provinces. Following the metabolomics workflows, the samples from Sichuan
      and Jiangxi displayed distinct differences in their triterpene profiles, whereas
      those from Fujian showed remarkable intra-class variation. Twenty-three
      triterpenes were identified to contribute most to the differentiated clustering.
      A sensitive, precise, repeatable, and accurate quantitative assay method was
      established on a hybrid triple quadrupole-linear ion trap mass spectrometer to
      quantify the contents of eight triterpene compounds. Taking into account the
      metabolomics and quantitation results, alisol B 23-acetate and alisol A are
      significantly different in Alismatis Rhizoma from Sichuan and Jiangxi Provinces,
      and they may have the potential for geographic discrimination. These results
      illustrate how geographic difference impacts the triterpene chemistry of
      Alismatis Rhizoma. Metabolomics-driven chemical comparison is suitable for the
      quality evaluation of traditional Chinese medicine.

PMID- 29178375
TI  - Paracentral acute middle maculopathy as a finding in patients with severe vision
      loss following phacoemulsification cataract surgery: comment.

PMID- 29178374
TI  - Differential adult survival at close seabird colonies: The importance of spatial
      foraging segregation and bycatch risk during the breeding season.
AB  - Marine megafauna, including seabirds, are critically affected by fisheries
      bycatch. However, bycatch risk may differ on temporal and spatial scales due to
      the uneven distribution and effort of fleets operating different fishing gear,
      and to focal species distribution and foraging behavior. Scopoli's shearwater
      Calonectris diomedea is a long-lived seabird that experiences high bycatch rates
      in longline fisheries and strong population-level impacts due to this type of
      anthropogenic mortality. Analyzing a long-term dataset on individual monitoring,
      we compared adult survival (by means of multi-event capture-recapture models)
      among three close predator-free Mediterranean colonies of the species.
      Unexpectedly for a long-lived organism, adult survival varied among colonies. We
      explored potential causes of this differential survival by (1) measuring egg
      volume as a proxy of food availability and parental condition; (2) building a
      specific longline bycatch risk map for the species; and (3) assessing the
      distribution patterns of breeding birds from the three study colonies via GPS
      tracking. Egg volume was very similar between colonies over time, suggesting that
      environmental variability related to habitat foraging suitability was not the
      main cause of differential survival. On the other hand, differences in foraging
      movements among individuals from the three colonies expose them to differential
      mortality risk, which likely influenced the observed differences in adult
      survival. The overlap of information obtained by the generation of specific
      bycatch risk maps, the quantification of population demographic parameters, and
      the foraging spatial analysis should inform managers about differential
      sensitivity to the anthropogenic impact at mesoscale level and guide decisions
      depending on the spatial configuration of local populations. The approach would
      apply and should be considered in any species where foraging distribution is
      colony-specific and mortality risk varies spatially.

PMID- 29178376
TI  - A comparative meta-analysis on the relationship of faecal calcium and phosphorus
      excretion in mammals.
AB  - To investigate the relationship between faecal calcium (Ca) and phosphorus (P)
      excretion in different mammalian species, a meta-analysis on digestibility data
      derived from the literature was conducted. Seventy-three studies on carnivores,
      omnivores, large and small hindgut fermenters, ruminants and hippos (a total of
      21 mammalian species, precondition for inclusion dietary Ca/P ratio 1.5/1 -
      3.0/1) were analysed for Ca and P digestibility. Dietary Ca/P ratios were lower
      than faecal Ca/P ratios in carnivores, omnivores, ruminants and hippos. In
      hindgut fermenters, dietary Ca/P ratios were higher than faecal Ca/P ratios,
      indicating higher intestinal Ca absorption in these species. In all species
      investigated, there was a significant positive relationship between Ca intake and
      faecal Ca excretion and between P intake and faecal P excretion. In the
      biologically relevant range, these equations predicted lower faecal Ca losses in
      hindgut fermenters than ruminants, for faecal P vice versa. In all species,
      faecal Ca and P excretion correlated significantly. In carnivores, this highly
      linear correlation was exceptionally strong (R2 = .92). Yet, the linearity of the
      correlation was questionable in omnivores and ruminants. Possibly, the strong
      linear correlation of faecal Ca and P excretion in carnivores is due to the
      formation of insoluble Ca/P complexes in their relatively short and simple
      gastrointestinal tract. Another hypothesis is that in carnivores, Ca homeostasis
      relies on modifying bone turnover to a higher degree than on changes in
      intestinal Ca absorption. For the formation of bone matrix, a constant ratio of
      Ca and P absorption is of advantage.

PMID- 29178378
TI  - Editorial: Prevalence of Arthritis Revisited.

PMID- 29178377
TI  - Examination of the World Health Organization Disability Assessment System as a
      Measure of Disability Severity Among Veterans Receiving Cognitive Processing
      Therapy.
AB  - Cognitive processing therapy (CPT) is effective for reducing posttraumatic stress
      disorder (PTSD) and depression among military veterans. However, studies have not
      examined whether CPT is associated with reductions in disability severity. The
      current study examines the association between disability severity and PTSD and
      depression among U.S. veterans who are receiving CPT. Veterans completed measures
      at pre- and posttreatment and received CPT through a Veterans Affairs PTSD
      outpatient (n = 155) or residential (n = 177) program. The World Health
      Organization Disability Assessment Schedule (WHODAS) 2.0 was used to assess
      disability severity. The WHODAS 2.0 scores were positively correlated with
      clinician- and veteran-rated PTSD and veteran-rated depression at pre- and
      posttreatment (r = .22 to. 60). Compared with outpatients, veterans in
      residential treatment had worse scores on the WHODAS Mobility scale (etap2 =
      .03), but on no other WHODAS 2.0 scales. Pre- to posttreatment reductions were
      found on all WHODAS 2.0 subscales (etap2 = .03 to .15). Reductions in PTSD and
      depression were positively associated with improvements on the WHODAS 2.0 Summary
      scale and most subscales (r = .22 to. 52). Findings suggest that the WHODAS 2.0
      is a promising disability severity measure for veterans in PTSD treatment.
      Findings also suggest that CPT may help veterans to achieve reductions in
      disability severity.

PMID- 29178380
TI  - Current matters of the heart.

PMID- 29178379
TI  - Successful treatment of thrombotic microangiopathy associated with dengue
      infection: A case report and literature review.
AB  - Dengue infection has been associated with multiple renal complications, including
      glomerulonephritis, acute tubular necrosis, tubulointerstitial nephritis, and
      thrombotic microangiopathy (TMA), this last one being a rare complication of
      dengue, with only a few reported cases. TMA associated with dengue can be
      explained by an alteration in the activity of the enzyme ADAMTS13, leading to
      thrombotic thrombocytopenic purpura; or it can be secondary to direct or indirect
      endothelial injury by the virus, which leads to hemolytic uremic syndrome. Here,
      we present a case of severe TMA, not related to ADAMTS13, which was clearly
      associated with dengue infection.

PMID- 29178381
TI  - A retrospective evaluation of 128 socket-shield cases in the esthetic zone and
      posterior sites: Partial extraction therapy with up to 4 years follow-up.
AB  - OBJECTIVES: Tooth loss results in an inevitable alveolar ridge reduction. This
      has established a cautionary approach to extract, wait, augment, and insert the
      implant, in lieu of immediate placement. However, saving the tooth or part of it
      whenever possible is more conservative and supports the vital periodontal tissue
      buccofacial to an implant. The purpose of this cases series was to report on
      implant survival using this technique in a large cohort of patients at mid-term
      follow-up. MATERIALS AND METHODS: A private practice patient database was
      searched for all patients having received socket-shield treatment in conjunction
      with immediate implant placement. Of the results returned, 128 met the inclusion
      criteria of >=12 months from date of restoration, or failing prior to definitive
      restoration. These patients were recalled for evaluation of the restored implants
      up to 4 years post-treatment. RESULTS: Seventy immediate implants with socket
      shields were placed in female patients and 58 in males, age range 24-71 (mean 39
      years). The distribution of sites treated were: maxillary incisors (64%),
      premolars (22%), canines (14%); maxilla (89.9%), mandible (10.1%). 123/128
      implants osseointegrated and survived 1-4 years following restoration (survival
      rate 96.1%). A combined complication rate of 25/128 implants occurred (19.5%).
      Five implants failed to osseointegrate and were removed. The remaining 20
      complications were all managed or observed without management, with implants
      surviving at mid-term follow-up. CONCLUSIONS: Notwithstanding technique
      sensitivity and the need for randomized control studies, this case series
      demonstrates that the socket-shield performs competitively when compared to
      implant survival rates in both conventional immediate and delayed implant
      placement.

PMID- 29178382
TI  - Experimental and DFT Studies of the Electron-Withdrawing Ability of
      Perfluoroalkyl (RF ) Groups: Electron Affinities of PAH(RF )n Increase
      Significantly with Increasing RF Chain Length.
AB  - Two series of aromatic compounds with perfluoroalkyl (RF ) groups of increasing
      length, 1,3,5,7-naphthalene(RF )4 and 1,3,5,7,9-corannulene(RF )5 , have been
      prepared and their electronic properties studied by low-temperature photoelectron
      spectroscopy (PES) (for gas-phase electron affinity measurements). These and many
      related compounds were also studied by DFT calculations. The data demonstrate
      unambiguously that the electron-withdrawing ability of RF substituents increases
      significantly and uniformly from CF3 to C2 F5 to n-C3 F7 to n-C4 F9 .

PMID- 29178383
TI  - Thermochemical Insights into Fullerene Aggregation and the Phthalocyanine
      Fullerene Interaction in Efficient Solvents.
AB  - The physicochemical behavior of fullerene C60 in hydrocarbon solvents is examined
      by isothermal titration calorimetry, photocalorimetry, and UV spectroscopy. The
      obtained data are summarized to substantiate the idea of the binary
      fullerene/solvent cluster as a colloidal nanoentity that moderates noncovalent
      interactions of the C60 molecule in solution. This idea serves to aid
      understanding of the complex physicochemical behavior of tert-butyl-substituted
      phthalocyanine in C60 -saturated o-xylene under illumination with low-energy
      photons. The proposed experimental approach, which focuses on concentrated
      solutions and is applicable to multicomponent systems, is discussed as a
      potential tool of materials science.

PMID- 29178384
TI  - Metal-Organic Frameworks as Platforms for Catalytic Applications.
AB  - Metal-organic frameworks (MOFs), also called porous coordination polymers,
      represent a class of crystalline porous materials built from organic linkers and
      metal ions/clusters. The unique features of MOFs, including structural diversity
      and tailorability as well as high surface area, etc., enable them to be a highly
      versatile platform for potential applications in many fields. Herein, an overview
      of recent developments achieved in MOF catalysis, including heterogeneous
      catalysis, photocatalysis, and eletrocatalysis over MOFs and MOF-based materials,
      is provided. The active sites involved in the catalysts are particularly
      emphasized. The challenges, future trends, and prospects associated with MOFs and
      their related materials for catalysis are also discussed.

PMID- 29178385
TI  - Predictors of visual outcome and the role of early vitrectomy in streptococcal
      endophthalmitis: comment.

PMID- 29178386
TI  - A new parameter-rich structure-aware mechanistic model for amino acid
      substitution during evolution.
AB  - Improvements in the description of amino acid substitution are required to
      develop better pseudo-energy-based protein structure-aware models for use in
      phylogenetic studies. These models are used to characterize the probabilities of
      amino acid substitution and enable better simulation of protein sequences over a
      phylogeny. A better characterization of amino acid substitution probabilities in
      turn enables numerous downstream applications, like detecting positive selection,
      ancestral sequence reconstruction, and evolutionarily-motivated protein
      engineering. Many existing Markov models for amino acid substitution in molecular
      evolution disregard molecular structure and describe the amino acid substitution
      process over longer evolutionary periods poorly. Here, we present a new model
      upgraded with a site-specific parameterization of pseudo-energy terms in a coarse
      grained force field, which describes local heterogeneity in physical constraints
      on amino acid substitution better than a previous pseudo-energy-based model with
      minimum cost in runtime. The importance of each weight term parameterization in
      characterizing underlying features of the site, including contact number, solvent
      accessibility, and secondary structural elements was evaluated, returning both
      expected and biologically reasonable relationships between model parameters. This
      results in the acceptance of proposed amino acid substitutions that more closely
      resemble those observed site-specific frequencies in gene family alignments. The
      modular site-specific pseudo-energy function is made available for download
      through the following website:
      https://liberles.cst.temple.edu/Software/CASS/index.html.

PMID- 29178387
TI  - Gallic Acid and Gallates in Human Health and Disease: Do Mitochondria Hold the
      Key to Success?
AB  - Gallic acid and gallate esters are widely used as dietary supplements or
      additives with clinical significances. Over the last few decades, a large number
      of publications have been reported stating the antioxidative, antiapoptotic,
      cardioprotective, neuroprotective, and anticancer properties of gallic acid and
      gallates, and mostly demonstrated their antioxidative or prooxidative properties
      influencing the reactive oxygen species (ROS) signaling networks. However, very
      little focus has been paid to clinical trials, and this restricted their use as a
      prescribed preventative supplement. Since mitochondria are the principal
      organelles responsible for ROS generation, we reviewed the existing literature of
      mitochondria-specific effects of gallates including ROS production, respiration,
      mitochondrial biogenesis, apoptosis, and the physico-chemical parameters
      affecting the outcome of gallate supplementation to various health scenarios such
      as cardiovascular diseases, neurodegeneration, hepatic ailments, or cancers. The
      major signaling pathways and the molecules targeted by gallic acid and its
      derivatives have also been discussed with emphasis on mitochondria as the target
      site. This review provides a better understanding of the effect of gallic acid
      and gallate esters on mitochondrial functions and in designing effective
      preventative measures against the onset of various diseases.

PMID- 29178388
TI  - Synthesis of Carbon Dots with Multiple Color Emission by Controlled
      Graphitization and Surface Functionalization.
AB  - Multiple-color-emissive carbon dots (CDots) have potential applications in
      various fields such as bioimaging, light-emitting devices, and photocatalysis.
      The majority of the current CDots to date exhibit excitation-wavelength-dependent
      emissions with their maximum emission limited at the blue-light region. Here, a
      synthesis of multiple-color-emission CDots by controlled graphitization and
      surface function is reported. The CDots are synthesized through controlled
      thermal pyrolysis of citric acid and urea. By regulating the thermal-pyrolysis
      temperature and ratio of reactants, the maximum emission of the resulting CDots
      gradually shifts from blue to red light, covering the entire light spectrum.
      Specifically, the emission position of the CDots can be tuned from 430 to 630 nm
      through controlling the extent of graphitization and the amount of surface
      functional groups, ?COOH. The relative photoluminescence quantum yields of the
      CDots with blue, green, and red emission reach up to 52.6%, 35.1%, and 12.9%,
      respectively. Furthermore, it is demonstrated that the CDots can be uniformly
      dispersed into epoxy resins and be fabricated as transparent CDots/epoxy
      composites for multiple-color- and white-light-emitting devices. This research
      opens a door for developing low-cost CDots as alternative phosphors for light
      emitting devices.

PMID- 29178389
TI  - Mass spectrometry of aerosol particle analogues in molecular beam experiments.
AB  - Nanometer-size particles such as ultrafine aerosol particles, ice nanoparticles,
      water nanodroplets, etc, play an important, however, not yet fully understood
      role in the atmospheric chemistry and physics. These species are often composed
      of water with admixture of other atmospherically relevant molecules. To mimic and
      investigate such particles in laboratory experiments, mixed water clusters with
      atmospherically relevant molecules can be generated in molecular beams and
      studied by various mass spectrometric methods. The present review demonstrates
      that such experiments can provide unprecedented details of reaction mechanisms,
      and detailed insight into the photon-, electron-, and ion-induced processes
      relevant to the atmospheric chemistry. After a brief outline of the molecular
      beam preparation, cluster properties, and ionization methods, we focus on the
      mixed clusters with various atmospheric molecules, such as hydrated sulfuric acid
      and nitric acid clusters, Nx Oy and halogen-containing molecules with water. A
      special attention is paid to their reactivity and solvent effects of water
      molecules on the observed processes.

PMID- 29178390
TI  - FOXO protects against age-progressive axonal degeneration.
AB  - Neurodegeneration resulting in cognitive and motor impairment is an inevitable
      consequence of aging. Little is known about the genetic regulation of this
      process despite its overriding importance in normal aging. Here, we identify the
      Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of
      neuronal integrity by inhibiting age-progressive axonal degeneration in mammals.
      FOXO expression progressively increased in aging human and mouse brains. The
      nervous system-specific deletion of Foxo transcription factors in mice
      accelerates aging-related axonal tract degeneration, which is followed by motor
      dysfunction. This accelerated neurodegeneration is accompanied by levels of white
      matter astrogliosis and microgliosis in middle-aged Foxo knockout mice that are
      typically only observed in very old wild-type mice and other aged mammals,
      including humans. Mechanistically, axonal degeneration in nerve-specific Foxo
      knockout mice is associated with elevated mTORC1 activity and accompanying
      proteotoxic stress due to decreased Sestrin3 expression. Inhibition of mTORC1 by
      rapamycin treatment mimics FOXO action and prevented axonal degeneration in Foxo
      knockout mice with accelerated nervous system aging. Defining this central role
      for FOXO in neuroprotection during mammalian aging offers an invaluable window
      into the aging process itself.

PMID- 29178392
TI  - SLC34A2 regulates miR-25-Gsk3beta signaling pathway to affect tumor progression
      in gastric cancer stem cell-like cells.
AB  - A novel paradigm in tumor biology suggests that gastric cancer progression is
      driven by gastric cancer stem cell-like cells (GCSCs), but molecular mechanisms
      regulating tumorigenic and self-renewal potential of GCSCs are still unclear.
      Here, we aim to investigate biological function of SLC34A2 in regulating sphere
      formation and tumorigenicity (both are the hallmark of CSCs) of GCSCs and its
      underlying mechanisms. Our findings testified that CD44+ cells which were derived
      from fresh primary gastric cancer samples and cell lines displayed stem cell-like
      features. Significantly, SLC34A2 is increased in CD44+ GCSCs compared with those
      in adherent counterpart from CD44+ GCSCs. On clinic, SLC34A2 is overexpressed in
      primary tumor tissues compared with adjacent counterparts. We showed that SLC34A2
      regulated sphere formation and self-renewal properties of CD44+ GCSCs in vitro
      and in vivo. Mechanistic investigations revealed that Gsk3beta was the most
      strikingly up-regulated gene in response to SLC34A2 knockdown in GCSCs and
      Wnt/beta-cantenin signaling was required for SLC34A2-mediated sphere formation.
      Furthermore, SLC34A2 directly binds specific sites in the miR-25 promoter region
      and that the promoter activity is decreased after the mutation of putative
      SLC34A2-binding sites, indicating that SLC34A2 is required for the
      transcriptional induction of miR-25. Meanwhile, luciferase assays showed that miR
      25 directly targeted Gsk3beta in CD44+ GCSCs. Overall, our findings define a
      SLC34A2-miR-25-Gsk3beta pathway in the regulation of GCSCs features and gastric
      cancer progression, with potential therapeutic applications in blocking their
      progression.

PMID- 29178393
TI  - What makes a good head positioner for preventing occipital pressure ulcers.
AB  - Patients who are stationary endure prolonged soft tissue distortions and
      deformations at contact areas between their body and the support surface, which
      may lead to the onset of pressure ulcers (PUs) over time. A novel technology for
      patient positioning employs innovation in materials science, specifically
      viscoelastic materials with shape memory properties that compose the Z-FloTM head
      positioner (Molnlycke Health Care, Gothenburg, Sweden). Head positioners are
      generally known to reduce the occurrence of PUs in scalp tissues and the ears,
      but quantitative assessments of their biomechanical efficacy are missing in the
      literature. To determine potential differences in mechanical loads formed in the
      soft tissues of the back of the head while in contact with 2 head positioner
      types, Z-Flo vs flat medical foam, we developed 2 comparable finite element model
      configurations, both including the same 3-dimensional adult head. For both model
      variants, stresses in skin and fat peaked at the occiput. The skin at the back of
      the resting head is subjected to greater stress values with respect to fat;
      however, the Z-Flo positioner reduced the exposure of both skin and fat tissues
      to elevated stresses considerably (by a factor of 3) compared to the medical foam
      support. We found the Z-Flo device effective in reducing tissue loads at the
      surface of the head as well as internally in scalp tissues, with a particular
      strength in reducing internal tissue shear. The Z-Flo device achieves this
      protective quality through highly effective immersion and envelopment of the back
      of the head, generated in the process of manual moulding of the device in
      preparation for use. Additional protection is achieved through the viscoelastic
      response of the filling material of this positioner, which relaxes promptly and
      considerably under the weight of the head (by more than 2-fold within
      approximately 1 s) as opposed to the elastic recoil of the foam that pushes back
      on scalp tissues.

PMID- 29178391
TI  - Peptidoglycan in obligate intracellular bacteria.
AB  - Peptidoglycan is the predominant stress-bearing structure in the cell envelope of
      most bacteria, and also a potent stimulator of the eukaryotic immune system.
      Obligate intracellular bacteria replicate exclusively within the interior of
      living cells, an osmotically protected niche. Under these conditions
      peptidoglycan is not necessarily needed to maintain the integrity of the
      bacterial cell. Moreover, the presence of peptidoglycan puts bacteria at risk of
      detection and destruction by host peptidoglycan recognition factors and
      downstream effectors. This has resulted in a selective pressure and opportunity
      to reduce the levels of peptidoglycan. In this review we have analysed the
      occurrence of genes involved in peptidoglycan metabolism across the major
      obligate intracellular bacterial species. From this comparative analysis, we have
      identified a group of predicted 'peptidoglycan-intermediate' organisms that
      includes the Chlamydiae, Orientia tsutsugamushi, Wolbachia and Anaplasma
      marginale. This grouping is likely to reflect biological differences in their
      infection cycle compared with peptidoglycan-negative obligate intracellular
      bacteria such as Ehrlichia and Anaplasma phagocytophilum, as well as obligate
      intracellular bacteria with classical peptidoglycan such as Coxiella, Buchnera
      and members of the Rickettsia genus. The signature gene set of the peptidoglycan
      intermediate group reveals insights into minimal enzymatic requirements for
      building a peptidoglycan-like sacculus and/or division septum.

PMID- 29178394
TI  - Maturation in auditory event-related potentials explains variation in language
      ability in children.
AB  - Processing of auditory information in the cortex continues to develop into later
      childhood and adolescence. Recent research has indicated that intraclass
      correlation (ICC) is the best method for capturing maturation in auditory event
      related potentials (AEPs) of school-age children. However, the sensitivity of the
      ICC approach in discerning AEP changes in children has not been consistently
      demonstrated and positive results have not been replicated. We attempted this
      replication and further explored whether AEP maturation estimated using the ICC
      approach predicts cognitive and linguistic abilities in addition to chronological
      age. We measured AEPs in response to simple tones in groups of 7-, 8-, 9- and 10
      year olds with typical development (N = 67) and used ICC to estimate the age
      equivalent of each child's AEP (AEP-age). Results indicated that ICC
      differentiated 7- to 8-year-old children from 9- to 10-year-old children and that
      AEP-age predicted both chronological age and significant, unique variance in
      language ability, but not in nonverbal IQ. Our findings support the view that
      auditory organization in children reflects both general developmental maturation
      and more specific development of language skills, and support the future use of
      AEP-age to identify and understand individual differences in brain maturation in
      typically developing and clinical populations.

PMID- 29178395
TI  - Megafaunal effects on vegetation structure throughout a densely wooded African
      landscape.
AB  - Megafauna strongly affect vegetation structure and composition, often leading to
      management concern. However, the extent of their influence across large scales
      and varying ecosystems remains largely unknown. Using high resolution airborne
      Light Detection and Ranging (LiDAR), we investigated landscape-scale changes in
      vegetation height and three-dimensional (3D) structure across landscapes of
      varying elephant densities and presence over time, and in response to surface
      water distribution and terrain variability in the heavily managed thicket biome
      of the Addo Elephant National Park, South Africa. Elephants caused up to a
      fourfold reduction in vegetation height and altered the vertical profile, but
      increased vegetation height variability. Vegetation height also increased with
      elevation and distance from water, particularly in areas that elephants had long
      occupied at high densities. Slope had opposing effects on vegetation height, with
      height increasing with slope in areas long exposed to elephants, but decreasing
      where elephants had only recently been granted access. Our results suggest that
      elephants are the primary agents of vegetation change in this ecosystem, but that
      the strength of their effects varies across the landscape, enabling management to
      use water and terrain as mitigation tools. We further highlight the necessity of
      landscape-level experimental studies on megafaunal effects to untangle mechanisms
      and establish causality.

PMID- 29178396
TI  - Dermoscopic features of endocrine mucin-producing sweat gland carcinoma.
AB  - Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is very rare, with only
      61 cases reported to date. EMPSGC is considered to be a low-grade carcinoma of
      sweat gland origin. Dermoscopic findings of EMPSGC have not been previously
      reported. We report the first case of a man with EMPSGC, featuring dermoscopic
      findings. Dermoscopic examinations of the present EMPSGC lesion revealed tumor
      cell proliferation that appeared as pink ovoid nests and elongated epidermis that
      resembled a whitish-pink network. Another characteristic finding of the present
      lesion was the large red/blue globules in pink ovoid nests in the tumor. Those
      reflected lacunae containing secretory fluid with red blood cells. We think that
      the large red/blue globules in pink ovoid nests in our case could be a
      characteristic dermoscopic finding specific to EMPSGC. We dermatologists
      encounter many "pink nodules" at out-patient clinics. The present dermoscopic
      findings may be useful for the differential diagnosis of EMPSGC.

PMID- 29178397
TI  - Review: The transcripts associated with organ allograft rejection.
AB  - The molecular mechanisms operating in human organ transplant rejection are best
      inferred from the mRNAs expressed in biopsies because the corresponding proteins
      often have low expression and short half-lives, while small non-coding RNAs lack
      specificity. Associations should be characterized in a population that rigorously
      identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is
      best achieved in kidney transplant biopsies, but the results are generalizable to
      heart, lung, or liver transplants. Associations can be universal (all rejection),
      TCMR-selective, or ABMR-selective, with universal being strongest and ABMR
      selective weakest. Top universal transcripts are IFNG-inducible (eg, CXCL11 IDO1,
      WARS) or shared by effector T cells (ETCs) and NK cells (eg, KLRD1, CCL4). TCMR
      selective transcripts are expressed in activated ETCs (eg, CTLA4, IFNG),
      activated (eg, ADAMDEC1), or IFNG-induced macrophages (eg, ANKRD22). ABMR
      selective transcripts are expressed in NK cells (eg, FGFBP2, GNLY) and
      endothelial cells (eg, ROBO4, DARC). Transcript associations are highly
      reproducible between biopsy sets when the same rejection definitions, case mix,
      algorithm, and technology are applied, but exact ranks will vary. Previously
      published rejection-associated transcripts resemble universal and TCMR-selective
      transcripts due to incomplete representation of ABMR. Rejection-associated
      transcripts are never completely rejection-specific because they are shared with
      the stereotyped response-to-injury and innate immunity.

PMID- 29178398
TI  - Successful treatment of chromoblastomycosis of 10-year duration due to Fonsecaea
      nubica.
AB  - We report a case of chromoblastomycosis due to the presence of large plaque and
      verrucous hyperplasia lesions on the left upper limb, with elbow abnormal
      activities, in a 56-year-old male. The diagnosis of chromoblastomycosis was based
      on gross and microscopic morphologies, histopathological examination and clinical
      manifestation. Molecular tools were applied to identifying the causative agent
      Fonsecaea nubica, which is rarely reported to be associated with
      chromoblastomycosis. The patient was initially treated orally with terbinafine
      (250 mg/day) and itraconazole (200 mg/day), subsequently patient received
      thermotherapy (45-50 degrees C, 3 h/day) for 1 month. The patient was
      successfully cured. A literature review was performed to assess general features,
      treatment and outcome of chromoblastomycosis due to F.  nubica. All the 5
      reviewed patients were male, over 30 years old and their lesions occurred after
      traumatic inoculation.

PMID- 29178399
TI  - Cascade Production of Lactic Acid from Universal Types of Sugars Catalyzed by
      Lanthanum Triflate.
AB  - Lignocellulosic biomass conversion into value-added platform chemicals in the non
      toxic, water-tolerant Lewis acid, and water solutions bears the hallmark of green
      chemistry. Lactic acid derived from biomass is an important chemical building
      block for biodegradable polymers such as polylactide. Herein, a universal method
      of converting lignocellulosic sugars into lactic acid using catalytic amount of
      water-stable Lewis acid La(OTf)3 is demonstrated. The lignocellulosic sugars
      studied in this work include 1) pyrolytic sugars from pyrolysis oil, and 2)
      sugars derived from ionic liquid (IL)-pretreated biomass. Under moderate
      conditions (250  degrees C, 1 h), levoglucosan (major pyrolytic sugar), glucose,
      and xylose were converted into lactic acid with carbon-based molar yields of 75,
      74, and 61 %, respectively. Furthermore, roughly 49 mol % (based on levoglucosan)
      and 74 wt % (relative to pretreated biomass) of lactic acid were obtained from
      the conversion of pyrolytic sugars and sugar-rich fraction after lignin removal
      from switchgrass, respectively. To our knowledge, this is the first reported
      conversion of pyrolytic sugar into lactic acid by chemocatalysis and also
      lignocellulosic sugars are converted into lactic acid without hydrolysis. This
      approach could potentially be extended to other lignocellulosic sugars after
      simple removal of lignin from biomass pretreatment, rendering moderate to high
      yields of lactic acid.

PMID- 29178400
TI  - Evaluating clinical stop-smoking services globally: towards a minimum data set.
AB  - BACKGROUND AND AIMS: Behavioural and pharmacological support for smoking
      cessation improves the chances of success and represents a highly cost-effective
      way of preventing chronic disease and premature death. There is a large number of
      clinical stop-smoking services throughout the world. These could be connected
      into a global network to provide data to assess what treatment components are
      most effective, for what populations and in what settings. To enable this, a
      minimum data set (MDS) is required to standardize the data captured from smoking
      cessation services globally. METHODS: We describe some of the key steps involved
      in developing a global MDS for smoking cessation services and methodologies to be
      considered for their implementation, including approaches for reaching consensus
      on data items to include in a MDS and for its robust validation. We use informal
      approximations of these methods to produce an example global MDS for smoking
      cessation. Our aim with this is to stimulate further discussion around the
      development of a global MDS for smoking cessation services. RESULTS: Our example
      MDS comprises three sections. The first is a set of data items characterizing
      treatments offered by a service. The second is a small core set of data items
      describing clients' characteristics, engagement with the service and outcomes.
      The third is an extended set of client data items to be captured in addition to
      the core data items wherever resources permit. CONCLUSIONS: There would be
      benefit in establishing a minimum data set (MDS) to standardize data captured for
      smoking cessation services globally. Once implemented, a formal MDS could provide
      a basis for meaningful evaluations of different smoking cessation treatments in
      different populations in a variety of settings across many countries.

PMID- 29178401
TI  - Childhood cancer incidence and survival in Japan and England: A population-based
      study (1993-2010).
AB  - The present study aimed to compare cancer incidence and trends in survival for
      children diagnosed in Japan and England, using population-based cancer registry
      data. The analysis was based on 5192 children with cancer (age 0-14 years) from 6
      prefectural cancer registries in Japan and 21 295 children diagnosed in England
      during 1993-2010. Differences in incidence rates between the 2 countries were
      measured with Poisson regression models. Overall survival was estimated using the
      Kaplan-Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing
      sarcomas in England were more than twice as high as those in Japan. Incidence of
      germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML)
      was higher in Japan than in England. Incidence of all cancers combined decreased
      in Japan throughout the period 1993 to 2010, which was mainly explained by a
      decrease in registration of neuroblastoma in infants. For many cancers, 5-year
      survival improved in both countries. The improvement in survival in chronic
      myeloid leukemia (CML) was particularly dramatic in both countries. However, 5
      year survival remained less than 80% in 2005-2008 in both countries for AML,
      brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age
      1-14 years). There were significant differences in incidence of several cancers
      between countries, suggesting variation in genetic susceptibility and possibly
      environmental factors. The decrease in incidence for all cancers combined in
      Japan was related to the cessation of the national screening program for
      neuroblastoma. The large improvement in survival in CML coincided with the
      introduction of effective therapy (imatinib).

PMID- 29178402
TI  - Micro-Nanostructures of Cellulose-Collagen for Critical Sized Bone Defect
      Healing.
AB  - Bone tissue engineering strategies utilize biodegradable polymeric matrices alone
      or in combination with cells and factors to provide mechanical support to bone,
      while promoting cell proliferation, differentiation, and tissue ingrowth. The
      performance of mechanically competent, micro-nanostructured polymeric matrices,
      in combination with bone marrow stromal cells (BMSCs), is evaluated in a critical
      sized bone defect. Cellulose acetate (CA) is used to fabricate a porous
      microstructured matrix. Type I collagen is then allowed to self-assemble on these
      microstructures to create a natural polymer-based, micro-nanostructured matrix
      (CAc). Poly (lactic-co-glycolic acid) matrices with identical microstructures
      serve as controls. Significantly higher number of implanted host cells are
      distributed in the natural polymer based micro-nanostructures with greater bone
      density and more uniform cell distribution. Additionally, a twofold increase in
      collagen content is observed with natural polymer based scaffolds. This study
      establishes the benefits of natural polymer derived micro-nanostructures in
      combination with donor derived BMSCs to repair and regenerate critical sized bone
      defects. Natural polymer based materials with mechanically competent micro
      nanostructures may serve as an alternative material platform for bone
      regeneration.

PMID- 29178403
TI  - N-glycan engineering of a plant-produced anti-CD20-hIL-2 immunocytokine
      significantly enhances its effector functions.
AB  - Anti-CD20 recombinant antibodies are among the most promising therapeutics for
      the treatment of B-cell malignancies such as non-Hodgkin lymphomas. We recently
      demonstrated that an immunocytokine (2B8-Fc-hIL2), obtained by fusing an anti
      CD20 scFv-Fc antibody derived from C2B8 mAb (rituximab) to the human interleukin
      2 (hIL-2), can be efficiently produced in Nicotiana benthamiana plants. The
      purified immunocytokine (IC) bearing a typical plant protein N-glycosylation
      profile showed a CD20 binding activity comparable to that of rituximab and was
      efficient in eliciting antibody-dependent cell-mediated cytotoxicity (ADCC) of
      human PBMC against Daudi cells, indicating its fuctional integrity. In this work,
      the immunocytokine devoid of the typical xylose/fucose N-glycosylation plant
      signature (IC-DeltaXF) and the corresponding scFv-Fc-DeltaXF antibody not fused
      to the cytokine, were obtained in a glyco-engineered DeltaXylT/FucT N.
      benthamiana line. Purification yields from agroinfiltrated plants amounted to 20
      35 mg/kg of leaf fresh weight. When assayed for interaction with FcgammaRI and
      FcgammaRIIIa, IC-DeltaXF exhibited significantly enhanced binding affinities if
      compared to the counterpart bearing the typical plant protein N-glycosylation
      profile (IC) and to rituximab. The glyco-engineered recombinant molecules also
      exhibited a strongly improved ADCC and complement-dependent cytotoxicity (CDC).
      Notably, our results demonstrate a reduced C1q binding of xylose/fucose carrying
      IC and scFv-Fc compared to versions that lack these sugar moieties. These results
      demonstrate that specific N-glycosylation alterations in recombinant products can
      dramatically affect the effector functions of the immunocytokine, resulting in an
      overall improvement of the biological functions and consequently of the
      therapeutic potential.

PMID- 29178404
TI  - The impact of rickets on growth and morbidity during recovery among children with
      complicated severe acute malnutrition in Kenya: A cohort study.
AB  - The effects of rickets on children recovery from severe acute malnutrition (SAM)
      are unknown. Rickets may affect both growth and susceptibility to infectious
      diseases. We investigated the associations of clinically diagnosed rickets with
      life-threatening events and anthropometric recovery during 1 year following
      inpatient treatment for complicated SAM. This was a secondary analysis of
      clinical trial data among non-human immunodeficiency virus-infected Kenyan
      children with complicated SAM (2-59 months) followed for 1 year posthospital
      discharge (ClinicalTrials.gov ID NCT00934492). The outcomes were mortality,
      hospital readmissions, and growth during 12 months. The main exposure was
      clinically diagnosed rickets at baseline. Of 1,778 children recruited, 230
      (12.9%, 95% CI [11.4, 14 .6]) had clinical signs of rickets at baseline.
      Enrolment at an urban site, height-for-age and head circumference-for-age z
      scores were associated with rickets. Rickets at study enrolment was associated
      with increased mortality (adjusted Hazard Ratio [aHR] 1.61, 95% CI [1.14, 2.27]),
      any readmission (aHR 1.37, 95% CI [1.09, 1.72]), readmission for severe pneumonia
      (aHR 1.37, 95% CI [1.05, 1.79]), but not readmission with diarrhoea (aHR 1.05,
      95% CI [0.73, 1.51]). Rickets was associated with increased height gain
      (centimetres), adjusted regression coefficient 0.19 (95% CI [0.10, 0.28]), but
      not changes in head circumference, mid-upper arm circumference, or weight.
      Rickets was common among children with SAM at urban sites and associated with
      increased risks of severe pneumonia and death. Increased height gain may have
      resulted from vitamin D and calcium treatment. Future work should explore
      possibility of other concurrent micronutrient deficiencies and optimal treatment
      of rickets in this high-risk population.

PMID- 29178405
TI  - Acoustophoretic separation of infected erythrocytes from blood plasma in a
      microfluidic platform using biofunctionalized, matched-impedance layers.
AB  - Acoustophoresis is rapidly gaining prominence in the field of cell manipulation.
      In recent years, researchers have extensively used this method for separating
      different types of cells from the bulk fluid. In this paper, we propose a novel
      acoustophoresis-based technique to capture infected or abnormal erythrocytes from
      blood plasma. A typical acoustic device consisting of a transducer assembly,
      microfluidic cavity, and a reflector is considered. Based on the concept of
      impedance matching, a pair of antibody-coated polystyrene layers is placed in the
      nodal regions of an acoustic field within the cavity. This technique allows bi
      directional migration of the suspended cells to the biofunctionalized surfaces.
      Therefore, simultaneous capture of infected erythrocytes on both the layers is
      feasible. Finite element method is used to model the pressure field as well as
      the motion of erythrocytes under the influence of acoustic radiation, drag, and
      gravitational forces. A parametric analysis is done by varying the excitation
      frequency, driving voltage, and the thickness of the polystyrene layers. The
      resulting changes in the pressure amplitude and field pattern are investigated.
      The erythrocyte collection efficiency, rate of collection, and the cell
      distribution on the layer surfaces are also determined under different field
      conditions. The occurrence of transient cavitation in the blood plasma-filled
      cavity at the chosen frequency is taken into account by using its threshold
      pressure value as the limiting factor of pressure amplitude. The study provides
      an insight into the phenomenon and serves as a guideline to fabricate low-cost,
      multifunctional rapid diagnostic devices based on acoustophoretic separation.

PMID- 29178406
TI  - Tsuji-Trost Reaction of Non-Derivatized Allylic Alcohols.
AB  - Palladium-catalyzed allylic substitution of non-derivatized enantioenriched
      allylic alcohols with a variety of uncharged N-, S-, C- and O-centered
      nucleophiles using a bidentate BiPhePhos ligand is described. A remarkable effect
      of the counter ion (X) of the XPd[kappa2 -BiPhePhos][eta3 -C3 H5 ] was observed.
      When ClPd[kappa2 -BiPhePhos][eta3 -C3 H5 ] (complex I) was used as catalyst, non
      reproducible results were obtained. Study of the complex by X-ray
      crystallography, 31 P NMR spectroscopy, and ESI-MS showed that a decomposition
      occurred where one of the phosphite ligands was oxidized to the corresponding
      phosphate, generating ClPd[kappa1 -BiPhePhosphite-phosphate][eta3 -C3 H5 ]
      species (complex II). When the chloride was exchanged to the weaker coordinating
      OTf- counter ion the more stable Pd[kappa2 -BiPhePhos][eta3 -C3 H5 ]+ +[OTf] -
      (complex III) was formed. Complex III performed better and gave higher
      enantiospecificities in the substitution reactions. Complex III was evaluated in
      Tsuji-Trost reactions of stereogenic non-derivatized allylic alcohols. The
      desired products were obtained in good to excellent yields (71-98 %) and
      enantiospecificities (73-99 %) for both inter- and intramolecular substitution
      reactions with only water generated as a by-product. The methodology was applied
      to key steps in total synthesis of (S)-cuspareine and (+)-lentiginosine. A
      reaction mechanism involving a palladium hydride as a key intermediate in the
      activation of the hydroxyl group is proposed in the overall transformation.

PMID- 29178407
TI  - A meta-analysis of the association between Helicobacter pylori (H. pylori)
      infection and hyperemesis gravidarum.
AB  - BACKGROUND: Hyperemesis gravidarum remains a common, distressing, and significant
      yet poorly understood disorder during pregnancy. The association between maternal
      Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum has been
      increasingly recognized and investigated. This study thus aimed to provide an
      updated review and meta-analysis of the topic. METHODS: Using the search terms
      (H. pyloriOR Helicobacter ORHelicobacter pyloriOR infection) AND (pregnancy OR
      emesis OR hyperemesis gravidarum OR nausea OR vomiting), a preliminary search on
      the PubMed, Ovid, Web of Science, Google Scholar, and WanFang database yielded
      372 papers published in English between January 1st, 1960 and June 1st, 2017.
      RESULTS: A total of 38 cross-sectional and case-control studies, with a total of
      10 289 patients were eligible for review. Meta-analysis revealed a significant
      association between H. pylori infection and hyperemesis gravidarum during
      pregnancy, with a pooled odds ratio of 1.348 (95% CI: 1.156-1.539, P < .001).
      Subgroup analysis found that serologic and stool antigen tests were comparable
      methods of detecting H. pylori as they yielded similar odds ratios. LIMITATIONS:
      Although the studies did not have high heterogeneity (I2  = 28%), publication
      bias was observed, and interstudy discrepancies in the diagnostic criteria
      adopted for hyperemesis gravidarum limit the reliability of findings. Also, 15 of
      the included studies were from the same country (Turkey), which could limit the
      generalizability of current findings. The prevalence of H. pylori infection
      varies throughout the world, and there may also be pathogenic differences as most
      strains of H. pylori in East Asia carry the cytotoxin-associated gene A gene.
      CONCLUSION: H. pylori infection was associated with an increased likelihood of
      hyperemesis gravidarum during pregnancy. Given the high prevalence of H. pylori
      infections worldwide, detecting H. pylori infection and the eradication of
      maternal H. pylori infection could be part of maternal hyperemesis gravidarum
      management. Further confirmation with robust longitudinal studies and mechanistic
      investigations are needed.

PMID- 29178408
TI  - Spousal recollections of early signs of primary progressive aphasia.
AB  - BACKGROUND: Although primary progressive aphasia (PPA) is characterized by
      progressive loss of language and communication skills, knowledge about the
      earliest emerging signs announcing the onset of this condition is limited. AIMS:
      To explore spousal recollections regarding the earliest signs of PPA and to
      compare the nature of the earliest perceived symptoms across the three PPA
      variants. METHODS & PROCEDURES: In-depth interviews focusing on the earliest
      signs of illness onset were conducted with 13 spouses whose partners were
      diagnosed with PPA. The earliest recollections and observations described by the
      spouses were analyzed and coded according to the DSM-5 criteria for a mild
      neurocognitive disorder. These data were then compared across and within each of
      the three PPA variants. OUTCOMES & RESULTS: Spousal retrospective accounts
      indicated the three PPA variants (semantic, logopenic and non-fluent) had a
      signature profile announcing illness onset. Changes in social cognition presented
      in all three variants of PPA, but at different points in the illness trajectory.
      In particular, the findings suggest the possibility that PPA initially presents
      as subtle changes in social cognition for semantic variant PPA (svPPA) and
      logopenic variant PPA (IvPPA) rather than overt language impairments as defined
      in the current diagnostic criteria. CONCLUSIONS & IMPLICATIONS: Understanding the
      nature of symptoms perceived in the earliest stages of PPA has potential to
      inform earlier and accurate diagnosis and interventions to assist those living
      with the illness.

PMID- 29178410
TI  - Genome sequences of Chlorella sorokiniana UTEX 1602 and Micractinium conductrix
      SAG 241.80: implications to maltose excretion by a green alga.
AB  - Green algae represent a key segment of the global species capable of
      photoautotrophic-driven biological carbon fixation. Algae partition fixed-carbon
      into chemical compounds required for biomass, while diverting excess carbon into
      internal storage compounds such as starch and lipids or, in certain cases, into
      targeted extracellular compounds. Two green algae were selected to probe for
      critical components associated with sugar production and release in a model alga.
      Chlorella sorokiniana UTEX 1602 - which does not release significant quantities
      of sugars to the extracellular space - was selected as a control to compare with
      the maltose-releasing Micractinium conductrix SAG 241.80 - which was originally
      isolated from an endosymbiotic association with the ciliate Paramecium bursaria.
      Both strains were subjected to three sequencing approaches to assemble their
      genomes and annotate their genes. This analysis was further complemented with
      transcriptional studies during maltose release by M. conductrix SAG 241.80 versus
      conditions where sugar release is minimal. The annotation revealed that both
      strains contain homologs for the key components of a putative pathway leading to
      cytosolic maltose accumulation, while transcriptional studies found few changes
      in mRNA levels for the genes associated with these established intracellular
      sugar pathways. A further analysis of potential sugar transporters found multiple
      homologs for SWEETs and tonoplast sugar transporters. The analysis of
      transcriptional differences revealed a lesser and more measured global response
      for M. conductrix SAG 241.80 versus C. sorokiniana UTEX 1602 during conditions
      resulting in sugar release, providing a catalog of genes that might play a role
      in extracellular sugar transport.

PMID- 29178411
TI  - Increased plasma oleoylethanolamide and palmitoleoylethanolamide levels correlate
      with inflammatory changes in alcohol binge drinkers: the case of HMGB1 in women.
AB  - Alcohol binge drinking is a heavy pattern of alcohol consumption increasingly
      used by young people. In a previous study, we reported that young drinkers with a
      2-year history of binge alcohol consumption had an overactivation of the innate
      immune system and peripheral inflammation when compared with controls. In the
      present study, we measured several biolipids that are fatty acid derivatives
      belonging to the acylethanolamide or 2-acylglycerol families in the plasma of the
      same subjects (n = 42; 20 men and 22 women). We found that during abstinence,
      alcohol binge drinkers had elevated plasma levels of oleoylethanolamide,
      palmitoleoylethanolamide, arachidonoylethanolamide, dihomo-gamma-linolenoyl
      ethanolamide and linoleoyl ethanolamide, which positively correlated with changes
      in the mRNA expression of key inflammatory markers in peripheral blood
      mononuclear cells, such as toll-like receptors (TLR4), pro-inflammatory
      cytokines/chemokines interleukin-1 beta, interleukin-6 and monocyte
      chemoattractant protein-1, and cyclooxygenase-2. Additionally, plasma
      oleoylethanolamide positively correlated with plasma levels of high mobility
      group box-1, which is a danger-associated molecular pattern and an endogenous
      TLR4 agonist, specifically in female alcohol binge drinkers. No changes were
      observed in 2-acylglycerols in alcohol binge drinkers, although sex-related
      differences in these bioactive lipids as well as in palmitoleoylethanolamide and
      docosatetraenoylethanolamide levels were detected. These results extend the
      previous clinical findings observed in patients diagnosed with long-term alcohol
      use disorder to young users and suggest a prominent role for these lipids in the
      response to acute alcohol exposure.

PMID- 29178409
TI  - Sox2 regulates astrocytic and vascular development in the retina.
AB  - Sox2 is a transcriptional regulator that is highly expressed in retinal
      astrocytes, yet its function in these cells has not previously been examined. To
      understand its role, we conditionally deleted Sox2 from the population of
      astrocytes and examined the consequences on retinal development. We found that
      Sox2 deletion does not alter the migration of astrocytes, but it impairs their
      maturation, evidenced by the delayed upregulation of glial fibrillary acidic
      protein (GFAP) across the retina. The centro-peripheral gradient of angiogenesis
      is also delayed in Sox2-CKO retinas. In the mature retina, we observed lasting
      abnormalities in the astrocytic population evidenced by the sporadic loss of GFAP
      immunoreactivity in the peripheral retina as well as by the aberrant extension of
      processes into the inner retina. Blood vessels in the adult retina are also under
      developed and show a decrease in the frequency of branch points and in total
      vessel length. The developmental relationship between maturing astrocytes and
      angiogenesis suggests a causal relationship between the astrocytic loss of Sox2
      and the vascular architecture in maturity. We suggest that the delay in
      astrocytic maturation and vascular invasion may render the retina hypoxic,
      thereby causing the abnormalities we observe in adulthood. These studies uncover
      a novel role for Sox2 in the development of retinal astrocytes and indicate that
      its removal can lead to lasting changes to retinal homeostasis.

PMID- 29178412
TI  - Temperature-Directed Biocatalysis for the Sustainable Production of Aromatic
      Aldehydes or Alcohols.
AB  - The biosynthesis of aromatic aldehydes and alcohols from renewable resources is
      currently receiving considerable attention because of an increase in demand,
      finite fossil resources, and growing environmental concerns. Here, a temperature
      directed whole-cell catalyst was developed by using two novel enzymes from a
      thermophilic actinomycete. Ferulic acid, a model lignin derivative, was
      efficiently converted into vanillyl alcohol at a reaction temperature at 30 
      degrees C. However, when the temperature was increased to 50  degrees C, ferulic
      acid was mainly converted into vanillin with a productivity of 1.1 g L-1  h-1 .
      This is due to the fact that the redundant endogenous alcohol dehydrogenases
      (ADHs) are not active at this temperature while the functional enzymes from the
      thermophilic strain remain active. As the biocatalyst could convert many other
      renewable cinnamic acid derivatives into their corresponding aromatic
      aldehydes/alcohols, this novel strategy may be extended to generate a vast array
      of valuable aldehydes or alcohols.

PMID- 29178413
TI  - In vivo reflectance confocal microscopy in daily practice: Image features
      correlated to histopathology.
AB  - BACKGROUND: In vivo reflectance confocal microscopy (RCM) represents a promising
      technique for noninvasive visualization of skin lesions. In the clinical daily
      practice, doctors want to know the relationship between the RCM images and the
      skin pathological changes. OBJECTIVE: The aim of this study was to identify the
      basic skin pathological changes under RCM, and use RCM terminology to describe
      these pathological changes. METHODS: A total of 100 patients were recruited and
      were evaluated both by RCM and histopathologic examination. Ten healthy
      volunteers were also recruited as control. RCM examinations were done and
      biopsies of the lesions at the same site of RCM examination were performed for
      histopathology analysis. RESULTS: The pathological changes including
      hyperkeratosis, parakeratosis, acanthosis, papilloma, spongiosis, pustule,
      vacuolar degeneration, hyperpigmentation, changes of collagen fibers, and
      vascular changes can be imaged by RCM and corresponded well to their
      histopathology. RCM failed to find the atypical keratinocytes in two squamous
      cell carcinoma cases because of the hyperkeratosis and failed to find the
      vascular changes in one port wine stain cases because of the limitation of
      detecting depth. CONCLUSION: Features correlating well to histopathology are
      observed on RCM. RCM can be used as an auxiliary diagnosis tool for the clinical
      diagnosis.

PMID- 29178414
TI  - Developing and validating a multivariable prediction model to improve the
      diagnostic accuracy in determination of cervical versus endometrial origin of
      uterine adenocarcinomas: A prospective MR study combining diffusion-weighted
      imaging and spectroscopy.
AB  - BACKGROUND: A triage test to assist clinical decision-making on choosing primary
      chemoradiation for cervical carcinomas or primary surgery for endometrial
      carcinomas is important. PURPOSE OR HYPOTHESIS: To develop and validate a
      multiparametric prediction model based on MR imaging and spectroscopy in
      distinguishing adenocarcinomas of uterine cervical or endometrial origin. STUDY
      TYPE: Prospective diagnostic accuracy study. POPULATION: Eighty-seven women: 25
      cervical and 62 endometrial adenocarcinomas divided into training (n = 43;
      cervical/endometrial adenocarcinomas = 11/32) and validation (n = 44; 14/30)
      datasets. FIELD STRENGTH/SEQUENCE: The 3T diffusion-weighted (DW) MR imaging and
      MR spectroscopy. ASSESSMENT: Morphology, volumetric DW MR imaging and
      spectroscopy (MDS) scoring system with total points 0-5, based on presence of the
      following MR features assessed independently by two radiologists: (a) epicenter
      at the cervix, (b) rim enhancement, (c) disrupted cervical stromal integrity, (d)
      mean volumetric apparent diffusion coefficient values (ADCmean) higher than 0.98
      * 10-3 mm2 /s, (e) fatty acyl delta 1.3 ppm more than 161.92 mM. Histopathology
      as gold standard. STATISTICAL TESTS: Logistic regression and receiver operator
      characteristic (ROC) curves analysis. RESULTS: For both the training and
      validation datasets, the MDS score achieved an accuracy of 93.0% and 84.1%,
      significantly higher than that of morphology (88.4% and 79.5%), ADC value (74.4%
      and 68.2%), and spectroscopy (81.4% and 68.2%; P < 0.05 for all). The
      performances of the scoring were superior to the morphology in the training
      dataset (areas under the receiver operating characteristics curve [AUC] = 0.95
      vs. 0.89; P = 0.046), but not in the validation dataset (AUC = 0.90 vs. 0.85; P =
      0.289). DATA CONCLUSION: MDS score has potentials to improve distinguishing
      adenocarcinomas of cervical or endometrial origin, and warrants large-scale
      studies for further validation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3
      J. Magn. Reson. Imaging 2018;47:1654-1666.

PMID- 29178415
TI  - Risk of recurrence of sigmoid volvulus: a single-centre cohort study.
AB  - AIM: Sigmoid volvulus is a condition with a tendency to recur if treated
      conservatively. Little is known about the best type of treatment or when to
      perform definitive surgery. The aim of this study was to review treatment, and
      assess the outcome, of sigmoid volvulus in adult patients treated at a Swedish
      university hospital. METHOD: The medical records of patients treated for sigmoid
      volvulus at Sahlgrenska University Hospital, Sweden from January 2000 to
      September 2016 were reviewed retrospectively. Median follow-up time was 8.3
      years. RESULTS: One hundred and sixty-eight patients were included with a total
      of 453 admissions for sigmoid volvulus. Nonoperative decompression was attempted
      as the initial treatment in 438/453 (97%), with a success rate of 92% (403/438),
      which was not influenced by whether it was the first episode or a recurrence.
      Without planned surgery, recurrence occurred after 84% of successful nonoperative
      decompressions with a median of two recurrences (1-16). Recurrence was less
      common after the first episode compared with subsequent episodes. Median time
      until recurrence was 58 days. Mortality after planned surgery following
      successful decompression was 3.3% (2/61) compared with 13% (6/46) following
      emergency surgery. CONCLUSION: In our cohort, the recurrence rate of sigmoid
      volvulus following successful nonoperative decompression was high. Still, more
      than 20% of patients did not experience a recurrence after their first episode.
      Nonoperative decompression could thus be suggested as the sole treatment for the
      first episode of volvulus. However, after the second episode it is probable that
      early planned surgery would improve outcome and reduce health-care consumption.

PMID- 29178416
TI  - 2D Enzyme Cascade Network with Efficient Substrate Channeling by Swinging Arms.
AB  - In living cells, compartmentalized or membrane-associated enzymes are often
      assembled into large networks to cooperatively catalyze cascade reaction pathways
      essential for cellular metabolism. Here, we report the assembly of an artificial
      2D enzyme network of two cascade enzymes-glucose-6-phosphate dehydrogenase
      (G6PDH) and lactate dehydrogenase (LDH)-on a wireframe DNA origami template.
      Swinging arms were used to facilitate the transport of the redox intermediate of
      NAD+ /NADH between enzyme pairs on the array. The assemblies of 2D enzyme
      networks were characterized by gel electrophoresis and visualized by atomic force
      microscopy (AFM). The spatial arrangements of multiple enzyme pairs were
      optimized to facilitate efficient substrate channeling by exploiting the
      programmability of DNA origami to manipulate the key parameters of swinging arm
      length and stoichiometry. Compared with a single enzyme pair, the 2D organized
      enzyme systems exhibited higher reaction efficiency due to the promoted transfer
      of intermediates within the network.

PMID- 29178417
TI  - Risk of epilepsy in surgical patients undergoing general or neuraxial
      anaesthesia.
AB  - Limited information is available on the risks of epilepsy after surgery in
      patients receiving general or neuraxial anaesthesia. Using Taiwan's National
      Health Insurance Research Database, we identified 1,478,977 patients aged >= 20
      years who underwent surgery (required general or neuraxial anaesthesia with
      hospitalisation for more than one day) between 2004 and 2011. We selected 235,066
      patients with general anaesthesia and 235,066 patients with neuraxial anaesthesia
      using a frequency-matching procedure for age and sex. We did not study those with
      co-existing epilepsy-related risk factors. The adjusted rate ratios (RRs) and 95%
      confidence intervals (CIs) of newly diagnosed epilepsy 1 year after surgery
      associated with general anaesthesia were analysed in the multivariate Poisson
      regression model. The one-year incidence of postoperative epilepsy for patients
      with general anaesthesia and neuraxial anaesthesia were 0.41 and 0.32 per 1000
      persons, respectively, and the corresponding RR was 1.27 (95%CI 1.15-1.41). The
      association between general anaesthesia and postoperative epilepsy was
      significant in men (RR = 1.22; 95%CI 1.06-1.40), women (RR = 1.33; 95%CI 1.15
      1.55) and 20-39-year-old patients. The risk of postoperative epilepsy increased
      in patients with general anaesthesia who had co-existing medical conditions and
      postoperative complications.

PMID- 29178418
TI  - Dense-core vesicle biogenesis and exocytosis in neurons lacking chromogranins A
      and B.
AB  - Chromogranin A and B (Cgs) are considered to be master regulators of cargo
      sorting for the regulated secretory pathway (RSP) and dense-core vesicle (DCV)
      biogenesis. To test this, we analyzed the release of neuropeptide Y (NPY)
      pHluorin, a live RSP reporter, and the distribution, number, and appearance of
      DCVs, in mouse hippocampal neurons lacking expression of CHGA and CHGB genes. qRT
      PCR analysis showed that expression of other granin family members was not
      significantly altered in CgA/B-/- neurons. As synaptic maturation of developing
      neurons depends on secretion of trophic factors in the RSP, we first analyzed
      neuronal development in standardized neuronal cultures. Surprisingly, dendritic
      and axonal length, arborization, synapse density, and synaptic vesicle
      accumulation in synapses were all normal in CgA/B-/- neurons. Moreover, the
      number of DCVs outside the soma, stained with endogenous marker Secretogranin II,
      the number of NPY-pHluorin puncta, and the total amount of reporter in secretory
      compartments, as indicated by pH-sensitive NPY-pHluorin fluorescence, were all
      normal in CgA/B-/- neurons. Electron microscopy revealed that synapses contained
      a normal number of DCVs, with a normal diameter, in CgA/B-/- neurons. In
      contrast, CgA/B-/- chromaffin cells contained fewer and smaller secretory
      vesicles with a smaller core size, as previously reported. Finally, live-cell
      imaging at single vesicle resolution revealed a normal number of fusion events
      upon bursts of action potentials in CgA/B-/- neurons. These events had normal
      kinetics and onset relative to the start of stimulation. Taken together, these
      data indicate that the two chromogranins are dispensable for cargo sorting in the
      RSP and DCV biogenesis in mouse hippocampal neurons.

PMID- 29178419
TI  - Understanding aneurysmal type 1 neovascularization (polypoidal choroidal
      vasculopathy): a lesson in the taxonomy of 'expanded spectra' - a review.
AB  - The term aneurysmal type 1 neovascularization is derived from terminology, which
      is established in the literature but has fallen out of use. We believe that
      aneurysmal type 1 neovascularization accurately describes the lesions which
      define the entity known as polypoidal choroidal vasculopathy (PCV). Over the last
      three decades, the clinical spectrum of PCV has expanded to recognize the
      occurrence of the aneurysmal (polypoidal) lesions in different contexts,
      resulting in a complex and unwieldy taxonomy based sometimes on circumstantial
      findings rather than mechanistic considerations. Advances in multimodal imaging
      provides increasingly convincing evidence that the lesions which define various
      forms of PCV are indeed vascular and arise from type 1 neovascular networks. The
      understanding of PCV as type 1 neovascularization with aneurysms renews focus on
      the question as to why some patients with type 1 neovascularization develop
      aneurysms while others do not. Conceptual themes and potential for further study
      are discussed.

PMID- 29178420
TI  - Drooling is no early sign of dysphagia in Parkinson's disease.
AB  - BACKGROUND: Dysphagia is frequent and clinically highly relevant in Parkinson's
      disease (PD). For a rational dysphagia screening predictors are required.
      Previous investigations suggested that drooling correlates with dysphagia and may
      serve as its early sign. The aim of this study was to clarify the
      interrelationship of drooling and dysphagia. METHODS: In a controlled, cross
      sectional, observational study, a total of 119 Parkinson outpatients and 32
      controls were examined clinically and by flexible-endoscopic evaluation of
      swallowing (FEES). Drooling, dysphagia including retained pharyngeal secretions,
      and cognitive function were assessed by established evaluation scales. KEY
      RESULTS: Fifty percent of all PD patients but only 9% of controls had drooling (P
      < .001). Drooling and dysphagia were related in PD (P = .027) but the data do not
      support to view drooling as a hallmark symptom for critical dysphagia. Thirty
      nine percent of the patients with critical aspiration had no drooling. In
      contrast, 41% of the patients with severe drooling had no clinically relevant
      dysphagia in FEES. The oral, but not the pharyngeal secretion management was
      impaired in PD patients and there was no clear association between drooling and
      pharyngeal secretion accumulation. Cognitive impaired patients had significantly
      more drooling (P = .005). CONCLUSIONS & INFERENCES: Although frequent in PD,
      drooling and dysphagia are only weakly related and drooling cannot be viewed as
      an early sign of dysphagia. Our data further suggest that the underlying cause of
      drooling is located in the voluntary oral phase, which is negatively influenced
      by cognitive deficits.

PMID- 29178421
TI  - The identification of at-risk patients and prevention of venous thromboembolism
      in pediatric cancer: guidance from the SSC of the ISTH.

PMID- 29178422
TI  - Novel inactivating mutations of the DCAF17 gene in American and Turkish families
      cause male infertility and female subfertility in the mouse model.
AB  - Loss-of-function DCAF17 variants cause hypogonadism, partial alopecia, diabetes
      mellitus, mental retardation, and deafness with variable clinical presentation.
      DCAF17 pathogenic variants have been largely reported in the Middle Eastern
      populations, but the incidence in American families is rare and animal models are
      lacking. Exome sequencing in 5 women with syndromic hypergonadotropic
      hypogonadism from 2 unrelated families revealed novel pathogenic variants in the
      DCAF17 gene. DCAF17 exon 2 (c.127-1G > C) novel homozygous variants were
      discovered in 4 Turkish siblings, while 1 American was compound heterozygous for
      1-stop gain variant in exon 5 (c.C535T; p.Gln179*) and previously described stop
      gain variant in exon 9 (c.G906A; p.Trp302*). A mouse model mimicking loss of
      function in exon 2 of Dcaf17 was generated using CRISPR/Cas9 and showed female
      subfertility and male infertility. Our results identify 2 novel variants, and
      show that Dcaf17 plays a significant role in mammalian gonadal development and
      infertility.

PMID- 29178423
TI  - Effectiveness of lifestyle interventions for preventing harmful weight gain among
      young adults from lower socioeconomic status and ethnically diverse backgrounds:
      a systematic review.
AB  - The incidence of overweight and obesity are increasing with each successive
      generation of young adults. Associated co-morbidities will emerge at an earlier
      age unless weight gain is prevented. Evidence has demonstrated young adults (aged
      18-35 years) from low socioeconomic and ethnically diverse backgrounds are at
      greater risk of overweight or obesity, yet it is unclear how to effectively
      intervene in this population. This systematic review aimed to assess the
      effectiveness of lifestyle interventions conducted in this population. Thirty
      studies reporting on lifestyle interventions for prevention of weight gain were
      identified from eight electronic databases searched. Six interventions included
      subgroup analyses to determine if ethnicity moderated weight change, and two
      included subgroup analyses to determine if socioeconomic status had an effect on
      change in weight. Five of these six studies were effective in preventing weight
      gain, and subgroup analyses showed no differences in effect by ethnicity. Of
      these five studies, two included a subgroup analysis that showed socioeconomic
      status to have no effect on weight outcome. Despite the promising results from
      these five lifestyle interventions utilizing online and mobile components to
      effectively reach and prevent weight gain in this priority population, the
      evidence base of high quality trials is limited.

PMID- 29178425
TI  - Lateral sensitivity in electron probe microanalysis studied by Monte Carlo
      simulations involving fluorescence enhancements.
AB  - In electron probe microanalysis, secondary fluorescence can occur leading to an
      increase of the volume analysed, degrading the lateral resolution of this
      technique. An adequate knowledge of the interaction volumes from where the
      different signals of interest are detected is determinant to estimate the minimum
      size of the zone that can be characterized. In this work, the size of the signal
      source volume is surveyed for a wide set of samples at different beam energies.
      To this aim, the PENELOPE software package was chosen to run Monte Carlo
      simulations for several experimental situations in order to produce the various
      lateral radiation distributions of interest. A comparison between the interaction
      volumes of the different signals was performed by taking into account the
      different fluorescence enhancement possibilities. An unexpected behaviour was
      found in the particular cases of aluminium and alumina, where the secondary
      photons signal exhibits a decreasing trend up to certain beam energy (~17 keV);
      this implies that lower beam energies may degrade the lateral resolution of the
      technique in these materials.

PMID- 29178424
TI  - Does change in perceptions of peer teen dating violence predict change in teen
      dating violence perpetration over time?
AB  - Research has previously demonstrated that perceptions of peer's teen dating
      violence (TDV) is associated with one's own perpetration of TDV, although little
      research has examined whether this relationship is consistent across
      developmental time periods (i.e., mid-to-late adolescence). The present study
      examined whether changes in perceptions of peer's TDV predicted change in one's
      own perpetration of TDV in a sample of ethnically diverse adolescents from ages
      15 to 18 (N = 1,042). Parallel process modeling demonstrated that decreases in
      perceptions of peer's TDV predicted decreases in TDV perpetration over time, and
      this relationship was more pronounced for males than females. These findings lend
      further support to the need for TDV prevention and intervention programs to
      include peer influence in their programs.

PMID- 29178426
TI  - The role of sentinel lymph node mapping in small animal veterinary medicine: A
      comparison with current approaches in human medicine.
AB  - The relevance of regional lymph node (LN) assessment to quantify the metastatic
      spread of cancer is well recognized in veterinary oncology. Evaluation of LNs is
      critical for tumour staging. However, sampling the correct LN may not be possible
      without sentinel lymph node (SLN) mapping. Methods for diagnostic imaging and
      intraoperative detection of SLNs are well established in human medicine, in
      particular, the combination of lymphoscintigraphy and intraoperative application
      of blue dyes. Nevertheless, alternative imaging techniques are available and have
      gained increasing interest. Successful implementation of these techniques in dogs
      have been reported in both clinical and experimental studies. This review aims to
      provide an overview of SLN mapping techniques in human and veterinary medicine.

PMID- 29178428
TI  - Three-dimensional virtual cystoscopy: Noninvasive approach for the assessment of
      urinary tract in fetuses with lower urinary tract obstruction.

PMID- 29178427
TI  - CD38 modulates respiratory syncytial virus-driven proinflammatory processes in
      human monocyte-derived dendritic cells.
AB  - Respiratory syncytial virus (RSV) is the most common cause of hospitalization due
      to bronchiolitis in infants. Although the mechanisms behind this association are
      not completely elucidated, they appear to involve an excessive immune response
      causing lung pathology. Understanding the host response to RSV infection may help
      in the identification of targets for therapeutic intervention. We infected in
      vitro human monocyte-derived dendritic cells (DCs) with RSV and analysed various
      aspects of the cellular response. We found that RSV induces in DCs the expression
      of CD38, an ectoenzyme that catalyses the synthesis of cyclic ADPR (cADPR).
      Remarkably, CD38 was under the transcriptional control of RSV-induced type I
      interferon (IFN). CD38 and a set of IFN-stimulated genes (ISGs) were inhibited by
      the anti-oxidant N-acetyl cysteine. When CD38-generated cADPR was restrained by 8
      Br-cADPR or kuromanin, a flavonoid known to inhibit CD38 enzymatic activity, RSV
      induced type I/III IFNs and ISGs were markedly reduced. Taken together, these
      results suggest a key role of CD38 in the regulation of anti-viral responses.
      Inhibition of CD38 enzymatic activity may represent an encouraging approach to
      reduce RSV-induced hyperinflammation and a novel therapeutic option to treat
      bronchiolitis.

PMID- 29178429
TI  - Technical Note: Defining cyclotron-based clinical scanning proton machines in a
      FLUKA Monte Carlo system.
AB  - PURPOSE: Cyclotron-based pencil beam scanning (PBS) proton machines represent
      nowadays the majority and most affordable choice for proton therapy facilities,
      however, their representation in Monte Carlo (MC) codes is more complex than
      passively scattered proton system- or synchrotron-based PBS machines. This is
      because degraders are used to decrease the energy from the cyclotron maximum
      energy to the desired energy, resulting in a unique spot size, divergence, and
      energy spread depending on the amount of degradation. This manuscript outlines a
      generalized methodology to characterize a cyclotron-based PBS machine in a
      general-purpose MC code. The code can then be used to generate clinically
      relevant plans starting from commercial TPS plans. METHODS: The described beam is
      produced at the Provision Proton Therapy Center (Knoxville, TN, USA) using a
      cyclotron-based IBA Proteus Plus equipment. We characterized the Provision beam
      in the MC FLUKA using the experimental commissioning data. The code was then
      validated using experimental data in water phantoms for single pencil beams and
      larger irregular fields. Comparisons with RayStation TPS plans are also
      presented. RESULTS: Comparisons of experimental, simulated, and planned dose
      depositions in water plans show that same doses are calculated by both programs
      inside the target areas, while penumbrae differences are found at the field
      edges. These differences are lower for the MC, with a gamma(3%-3 mm) index never
      below 95%. CONCLUSIONS: Extensive explanations on how MC codes can be adapted to
      simulate cyclotron-based scanning proton machines are given with the aim of using
      the MC as a TPS verification tool to check and improve clinical plans. For all
      the tested cases, we showed that dose differences with experimental data are
      lower for the MC than TPS, implying that the created FLUKA beam model is better
      able to describe the experimental beam.

PMID- 29178430
TI  - Effects of female sex hormones on folic acid-induced anti-angiogenesis.
AB  - AIM: Pregnant women have been recommended to take FA daily to prevent birth
      defects in the brain and spinal cord. We previously showed that folic acid (FA)
      exerts an anti-angiogenic activity. As angiogenesis is important for endometrial
      reorganization and embryonic development, there should be some mechanisms to
      allow the pregnant mother and the foetus to escape from the FA-induced anti
      angiogenesis. This study was designed to investigate the effect of female sex
      hormones on the FA-induced anti-angiogenic activity. METHODS: The protein levels
      and protein-protein interaction were examined by Western blot analysis and
      immunoprecipitation assay respectively. The cell proliferation and migration were
      examined by MTT assay and wound healing assay respectively. The in vivo
      angiogenesis was evaluated by Matrigel angiogenesis assay. RESULTS: In human
      umbilical venous endothelial cells (HUVEC), FA receptor (FR) formed a complex
      with progesterone receptor (PR), oestradiol receptor (ER) and cSrc. Pregnancy
      levels of progesterone (P4) or oestradiol (E2) prevented FA-induced inhibitions
      of proliferation and migration in HUVEC. Both E2 and P4 prevented the FA-induced
      anti-angiogenesis in vivo. Moreover, cotreatment with FA and P4 or E2 inhibited
      the signalling pathways involved in FA-induced inhibitions of proliferation and
      migration in HUVEC. CONCLUSION: Female sex hormones interrupt the FA-induced anti
      angiogenic action through receptor-receptor interaction.

PMID- 29178431
TI  - Ionic-Liquid-Based Acidic Aqueous Biphasic Systems for Simultaneous Leaching and
      Extraction of Metallic Ions.
AB  - The first instance of an acidic aqueous biphasic system (AcABS) based on
      tributyltetradecyl phosphonium chloride ([P44414 ][Cl]) and an acid is here
      reported. This AcABS exhibits pronounced thermomorphic behavior and is shown to
      be applicable to the extraction of metal ions from concentrated acidic solutions.
      Metal ions such as cobalt(II), iron(III), platinum(IV) and nickel(II) are found
      to partition preferentially to one of the phases of the acidic aqueous biphasic
      system and it is here shown that it successfully allows the difficult separation
      of CoII from NiII , here studied at 24 and 50  degrees C.

PMID- 29178432
TI  - Acid and Base Resistant Zirconium Polyphenolate-Metalloporphyrin Scaffolds for
      Efficient CO2 Photoreduction.
AB  - A series of zirconium polyphenolate-decorated-(metallo)porphyrin metal-organic
      frameworks (MOFs), ZrPP-n (n = 1, 2), featuring infinite ZrIV -oxo chains linked
      via polyphenolate groups on four peripheries of eclipse-arranged porphyrin
      macrocycles, are successfully constructed through a top-down process from
      simulation to synthesis. These are the unusual examples of Zr-MOFs (or MOFs in
      general) based on phenolic porphyrins, instead of commonly known carboxylate
      based types. Representative ZrPP-1 not only exhibits strong acid resistance (pH =
      1, HCl) but also remains intact even when immersed in saturated NaOH solution
      (~20 m), an exceptionally large range of pH resistance among MOFs. The
      metallation at the porphyrin core gives rise to materials with enhanced sorption
      and catalytic properties. In particular, ZrPP-1-Co, with precise and uniform
      distribution of active centers, exhibits not only high CO2 trapping capability
      (~90 cm3 g-1 at 1 atm, 273 K, among the highest in Zr-MOFs) but also high
      photocatalytic activity for reduction of CO2 into CO (~14 mmol g-1 h-1 ) and high
      selectivity over CH4 (>96.4%) without any cocatalyst under visible-light
      irradiation (lambda > 420 nm). Given the strong chemical resistance under extreme
      alkali conditions, these catalysts can be recycled without appreciable loss of
      activity. The possible mechanism for photocatalytic reduction of CO2 -to-CO over
      ZrPP-1-Co is also proposed.

PMID- 29178433
TI  - Triptolide inhibits donor-specific antibody production and attenuates mixed
      antibody-mediated renal allograft injury.
AB  - Donor-specific antibodies (DSAs) are major mediators of renal allograft injury,
      and strategies to inhibit DSAs are important in promoting long-term graft
      survival. Triptolide exhibits a wide spectrum of antiinflammatory and
      immunosuppressive activities, and in autoimmune diseases it inhibits autoantibody
      levels. In this study, we investigated the suppressive role of triptolide in the
      generation of DSAs in transplant recipients. We found that triptolide treatment
      of skin allograft recipients in mice significantly suppressed the development of
      circulating anti-donor-specific IgG and effectively alleviated DSA-mediated renal
      allograft injury, which led to prolonged allograft survival. In vitro studies
      revealed that triptolide inhibited the differentiation of B cells into CD138+
      CD27++ plasma cells; reduced the levels of IgA, IgG, and IgM secreted by plasma
      cells; and repressed somatic hypermutation and class switch recombination of B
      cells. Moreover, triptolide-treated recipients showed reduced numbers of B cells,
      plasma cells, and memory B cells in spleens and decreased numbers of T, B,
      natural killer (NK) cells, and macrophages infiltrating grafts. These findings
      highlight the importance of triptolide in suppressing DSAs and establish
      triptolide as a novel therapeutic agent for antibody-mediated allograft
      rejection.

PMID- 29178434
TI  - Demonstration of an anti-hyperalgesic effect of a novel pan-Trk inhibitor PF
      06273340 in a battery of human evoked pain models.
AB  - AIM: Inhibitors of nerve growth factor (NGF) reduce pain in several chronic pain
      indications. NGF signals through tyrosine kinase receptors of the tropomyosin
      related kinase (Trk) family and the unrelated p75 receptor. PF-06273340 is a
      small molecule inhibitor of Trks A, B and C that reduces pain in nonclinical
      models, and the present study aimed to investigate the pharmacodynamics of this
      first-in-class molecule in humans. METHODS: A randomized, double-blind, single
      dose, placebo- and active-controlled five-period crossover study was conducted in
      healthy human subjects (NCT02260947). Subjects received five treatments: PF
      06273340 50 mg, PF-06273340 400 mg, pregabalin 300 mg, ibuprofen 600 mg and
      placebo. The five primary endpoints were the pain detection threshold for the
      thermal pain tests and the pain tolerance threshold for the cold pressor,
      electrical stair and pressure pain tests. The trial had predefined decision rules
      based on 95% confidence that the PF-06273340 effect was better than that of
      placebo. RESULTS: Twenty subjects entered the study, with 18 completing all five
      periods. The high dose of PF-06273340 met the decision rules on the ultraviolet
      (UV) B skin thermal pain endpoint [least squares (LS) mean vs. placebo: 1.13, 95%
      confidence interval: 0.64-1.61], but not on the other four primary endpoints. The
      low dose did not meet the decision criteria for any of the five primary
      endpoints. Pregabalin (cold pressor and electrical stair tests) and ibuprofen
      (UVB thermal pain) showed significant analgesic effects on expected endpoints.
      CONCLUSIONS: The study demonstrated, for the first time, the translation of
      nonclinical effects into man in an inflammatory pain analgesic pharmacodynamic
      endpoint using a pan-Trk inhibitor.

PMID- 29178435
TI  - In Vivo Therapeutic Effect of Vaccinium Meridionale Swartz in Ischemia
      Reperfusion Induced Male Albino Rats.
AB  - This study was aimed to investigate the cardioprotective and antioxidant effect
      of Vaccinium meridionale Swartz in ischemia-induced male albino Wistar strain
      rats. Rats were grouped into 5 of 6 numbers each. Group I served as a sham, group
      II served as control and group III, IV, and V served for 1, 10, and 25 mg/kg/d of
      an extract of Vaccinium meridionale Swartz for 15 consecutive days of treatment.
      Serum marker enzymes, lipid peroxidation, and myeloperoxidase were increased,
      whereas antioxidant enzymes were reduced in control due to injury. Increased
      phenol and anthocyanin contents and increased free radical scavenging activity
      was noted following treatment. Serum marker enzymes, necrosis, and lipid
      peroxidation, were reduced, whereas antioxidant enzymes and reduced glutathione
      were increased. Nitric oxide synthase and Akt expression were also increased
      following treatment. Taking all these data together, it is suggested that
      Vaccinium meridionale Swartz may be a potential therapeutic agent for the
      treatment of ischemic injury.

PMID- 29178436
TI  - Incremental Treatment Costs Attributable to Overweight and Obesity in Patients
      with Diabetes: Quantile Regression Approach.
AB  - OBJECTIVE: This study aimed to estimate treatment costs attributable to
      overweight and obesity in patients with diabetes who were less than 65 years of
      age in the United States. METHODS: This study used data from the Medical
      Expenditure Panel Survey from 2001 to 2013. Patients with diabetes were
      identified by using the International Classification of Diseases, Ninth Revision,
      Clinical Modification code (250), clinical classification codes (049 and 050), or
      self-reported physician diagnoses. Total treatment costs attributable to
      overweight and obesity were calculated as the differences in the adjusted costs
      compared with individuals with diabetes and normal weight. Adjusted costs were
      estimated by using generalized linear models or unconditional quantile regression
      models. RESULTS: The mean annual treatment costs attributable to obesity were
      $1,852 higher than those attributable to normal weight, while costs attributable
      to overweight were $133 higher. The unconditional quantile regression results
      indicated that the impact of obesity on total treatment costs gradually became
      more significant as treatment costs approached the upper quantile. CONCLUSIONS:
      Among patients with diabetes who were less than 65 years of age, patients with
      diabetes and obesity have significantly higher treatment costs than patients with
      diabetes and normal weight. The economic burden of diabetes to society will
      continue to increase unless more proactive preventive measures are taken to
      effectively treat patients with overweight or obesity.

PMID- 29178437
TI  - Skin color and tissue thickness effects on transmittance, reflectance, and skin
      temperature when using 635 and 808 nm lasers in low intensity therapeutics.
AB  - OBJECTIVE: To examine the role of skin color and tissue thickness on
      transmittance, reflectance, and skin heating using red and infrared laser light.
      METHODS: Forty volunteers were measured for skin color and skin-fold thickness at
      a standardized site near the elbow. Transmittance, reflectance and skin
      temperature were recorded for energy doses of 2, 6, 9, and 12 Joules using 635 nm
      (36 mW) and 808 nm (40 mW) wavelength laser diodes with irradiances within
      American National Standards Institute safety guidelines (4.88 mm diameter, 0.192
      W/cm2 and 4.88 mm diameter, 0.214 W/cm2 , respectively). RESULTS: The key factors
      affecting reflectance to an important degree were skin color and wavelength.
      However, the skin color effects were different for the two wavelengths:
      reflectance decreased for darker skin with a greater decrease for red light than
      near infrared light. Transmittance was greater using 808 nm compared with 635 nm.
      However, the effect was partly lost when the skin was dark rather than light, and
      was increasingly lost as tissue thickness increased. Dose had an increasing
      effect on temperature (0.7-1.6 degrees C across the 6, 9, and 12 J doses); any
      effects of wavelength, skin color, and tissue thickness were insignificant
      compared to dose effects. Subjects themselves were not aware of the increased
      skin temperature. Transmittance and reflectance changes as a function of energy
      were very small and likely of no clinical significance. Absorption did not change
      with higher energy doses and increasing temperature. CONCLUSION: Skin color and
      skin thickness affect transmittance and reflectance of laser light and must be
      accounted for when selecting energy dose to ensure therapeutic effectiveness at
      the target tissue. Skin heating appears not to be a concern when using 635 and
      808 nm lasers at energy doses of up to 12 J and irradiance within American
      National Standards Institute standards. Photobiomodulation therapy should never
      exceed the American National Standards Institute recommendation for the maximum
      permissible exposure to the skin. Lasers Surg. Med. 50:291-301, 2018. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29178438
TI  - Role of robotic approach for management of complicated jejunoileal diverticulosis
      - video vignette.
AB  - Jejunoileal diverticulosis (JID) is a rare condition with a reported incidence
      lower than 0.1% (1-3). Surgery is the definitive treatment for JID and can be
      considered to improve the patient's quality of life and to prevent further
      occurrence of severe symptoms (3, 4, 5). Minimally invasive approach facilitates
      postoperative recovery, lowers risks and improves outcomes in JID treatment (6).
      This article is protected by copyright. All rights reserved.

PMID- 29178439
TI  - Renal parenchyma impairment characterization in partial unilateral ureteral
      obstruction in mice with intravoxel incoherent motion-MRI.
AB  - Ureteropelvic junction obstruction constitutes a major cause of progressive
      pediatric renal disease. The biological mechanisms underlying the renal response
      to obstruction can be investigated using a clinically relevant mouse model of
      partial unilateral ureteral obstruction (pUUO). Renal function and kidney
      morphology data can be evaluated using renal ultrasound, scintigraphy and uro
      magnetic resonance imaging (uro-MRI), but these methods are poorly linked to
      histological change and not all are quantitative. Here, we propose to investigate
      pUUO for the first time using an intravoxel incoherent motion diffusion sequence.
      The aim of this study was to quantitatively characterize impairment of the kidney
      parenchyma in the pUUO model. This quantitative MRI method was able to assess the
      perfusion and microstructure of the kidney without requiring the injection of a
      contrast agent. The results suggest that a perfusion fraction (f) reduction is
      associated with a decrease in the volume of the renal parenchyma, which could be
      related to decreased renal vascularization. The latter may occur before
      impairment by fibrosis and the findings are in accordance with the literature
      using the UUO mice model and, more specifically, on pUUO. Further investigation
      is required before this technique can be made available for the diagnosis and
      management of children with antenatal hydronephrosis and to select the optimal
      timing of surgery if required.

PMID- 29178440
TI  - Invisible detergents for structure determination of membrane proteins by small
      angle neutron scattering.
AB  - A novel and generally applicable method for determining structures of membrane
      proteins in solution via small-angle neutron scattering (SANS) is presented.
      Common detergents for solubilizing membrane proteins were synthesized in isotope
      substituted versions for utilizing the intrinsic neutron scattering length
      difference between hydrogen and deuterium. Individual hydrogen/deuterium levels
      of the detergent head and tail groups were achieved such that the formed micelles
      became effectively invisible in heavy water (D2 O) when investigated by neutrons.
      This way, only the signal from the membrane protein remained in the SANS data. We
      demonstrate that the method is not only generally applicable on five very
      different membrane proteins but also reveals subtle structural details about the
      sarco/endoplasmatic reticulum Ca2+ ATPase (SERCA). In all, the synthesis of
      isotope-substituted detergents makes solution structure determination of membrane
      proteins by SANS and subsequent data analysis available to nonspecialists.

PMID- 29178441
TI  - Gene-based genetic association test with adaptive optimal weights.
AB  - It is well known that using proper weights for genetic variants is crucial in
      enhancing the power of gene- or pathway-based association tests. To increase the
      power, we propose a general approach that adaptively selects weights among a
      class of weight families and apply it to the popular sequencing kernel
      association test. Through comprehensive simulation studies, we demonstrate that
      the proposed method can substantially increase power under some conditions.
      Applications to real data are also presented. This general approach can be
      extended to all current set-based rare variant association tests whose
      performances depend on variant's weight assignment.

PMID- 29178442
TI  - The Effect of Food or Omeprazole on the Pharmacokinetics of Osimertinib in
      Patients With Non-Small-Cell Lung Cancer and in Healthy Volunteers.
AB  - Two phase 1, open-label studies assessed the impact of food or gastric pH
      modification (omeprazole) on the exposure and safety/tolerability of osimertinib
      and its metabolites. The food effect study was an open-label, 2-period crossover
      study in patients with advanced non-small-cell lung cancer, randomized into 2
      treatment sequences: single-dose osimertinib 80 mg in a fed then fasted state or
      fasted then fed. The gastric pH study was an open-label, 2-period fixed sequence
      study assessing the effect of omeprazole on osimertinib exposure in healthy male
      volunteers. In period 1, volunteers received omeprazole 40 mg (days 1-4), then
      omeprazole 40 mg plus osimertinib 80 mg (day 5). In period 2, volunteers received
      osimertinib 80 mg alone (single dose). Blood samples were collected at
      prespecified time points for pharmacokinetic analyses. Safety/tolerability was
      also assessed. In the food effect study 38 patients were randomized to fed/fasted
      (n = 18) or fasted/fed (n = 20) sequences with all patients completing treatment.
      Coadministration with food did not affect osimertinib exposure (geometric least
      squares mean ratios [90% confidence intervals]: 106.05% [94.82%, 118.60%] [area
      under the plasma concentration time curve from zero to 72 hours] and 92.75%
      [81.40%, 105.68%] [maximum plasma concentration]). In the gastric pH study (n =
      68 received treatment, n = 47 completed the study), coadministration with
      omeprazole did not affect osimertinib exposure (geometric least-squares mean
      ratios 106.66% [100.26%, 113.46%] [area under the concentration-time curve],
      101.65% [94.65%, 109.16%] [peak concentration]). Osimertinib was well tolerated
      in both studies. Osimertinib may be administered without regard to food. Dose
      restriction is not required in patients whose gastric pH may be altered by
      concomitant agents or medical conditions. ClinicalTrials.gov: NCT02224053,
      NCT02163733.

PMID- 29178444
TI  - Alemtuzumab versus interferon beta 1a for relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: Alemtuzumab is a humanised monoclonal antibody that alters the
      circulating lymphocyte pool, causing prolonged lymphopenia, thus remoulding the
      immune repertoire that accompanies homeostatic lymphocyte reconstitution. It has
      been proved more effective than interferon (IFN) 1a for the treatment of
      relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To compare the
      efficacy, tolerability and safety of alemtuzumab versus interferon beta 1a in the
      treatment of people with RRMS to prevent disease activity. SEARCH METHODS: We
      searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group
      Trials Register (1 February 2017) which, among other sources, contains records
      from CENTRAL, MEDLINE, Embase, CINAHL, LILACS, PEDRO and the trial registry
      databases Clinical Trials.gov and WHO International Clinical Trials Registry
      Platform for all prospectively registered and ongoing trials. SELECTION CRITERIA:
      All double-blind, randomised, controlled trials comparing intravenous alemtuzumab
      (12 mg per day or 24 mg per day on five consecutive days during the first month
      and on three consecutive days at months 12 and 24) versus subcutaneous IFN beta
      1a (22 MUg or 44 MUg three times per week (Rebif) or intramuscular injection 30
      MUg once a week (Avonex)) in people of any gender and age with RRMS. DATA
      COLLECTION AND ANALYSIS: We used standard methodological procedures expected by
      Cochrane. MAIN RESULTS: We included three trials involving 1694 participants. All
      trials compared alemtuzumab 12 mg per day or 24 mg per day versus IFN beta 1a for
      treating RRMS. In CAMMS223, participants received either subcutaneous IFN beta 1a
      44 MUg three times per week or annual intravenous cycles of alemtuzumab (at a
      dose of 12 mg per day or 24 mg per day) for 36 months. In CARE-MS I and CARE-MS
      II, participants received subcutaneous IFN beta 1a 44 MUg three times per week or
      annual intravenous cycles of alemtuzumab 12 mg per day for 24 months. The
      methodological quality was good for all three studies.In the alemtuzumab 12 mg
      per day group, the results showed statistically significant difference in
      reducing relapses (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.52 to
      0.70), preventing disease progression (RR 0.60, 95% CI 0.45 to 0.79) and
      developing new T2 lesions on magnetic resonance imaging (RR 0.75, 95% CI 0.61 to
      0.93) after 24 and 36 months' follow-up, but found no statistically significant
      difference in the changes of Expanded Disability Status Scale (EDSS) score (mean
      difference (MD) -0.35, 95% CI -0.73 to 0.03). In the alemtuzumab 24 mg per day
      group, the results showed statistically significant differences in reducing
      relapses (RR 0.38, 95% CI 0.23 to 0.62), preventing disease progression (RR 0.42,
      95% CI 0.21 to 0.84) and the changes of EDSS score (MD -0.83, 95% CI -1.17 to 
      0.49) after 36 months' follow-up.All three trials reported adverse events and
      serious adverse events. There was no statistically significant difference in the
      number of participants with at least one adverse event (RR 1.03, 95% CI 0.97 to
      1.08) and the number of participants who experienced serious adverse events (RR
      1.03, 95% CI 0.83 to 4.54). AUTHORS' CONCLUSIONS: There is low- to moderate
      quality evidence that annual intravenous cycles of alemtuzumab at a dose of 12 mg
      per day or 24 mg per day reduces the proportion of participants with relapses,
      disease progression, change of EDSS score and developing new T2 lesions on MRI
      over 24 to 36 months in comparison with subcutaneous IFN beta-1a 44 MUg three
      times per week.Alemtuzumab appeared to be relatively well tolerated. The most
      frequently reported adverse events were infusion-associated reactions, infections
      and autoimmune events. The use of alemtuzumab requires careful monitoring so that
      potentially serious adverse effects can be treated early and effectively.

PMID- 29178445
TI  - Pleistocene climatic changes drive diversification across a tropical savanna.
AB  - Spatial responses of species to past climate change depend on both intrinsic
      traits (climatic niche breadth, dispersal rates) and the scale of climatic
      fluctuations across the landscape. New capabilities in generating and analysing
      population genomic data, along with spatial modelling, have unleashed our
      capacity to infer how past climate changes have shaped populations, and by
      extension, complex communities. Combining these approaches, we uncover lineage
      diversity across four codistributed lizards from the Australian Monsoonal Tropics
      and explore how varying climatic tolerances interact with regional climate
      history to generate common vs. disparate responses to late Pleistocene change. We
      find more divergent spatial structuring and temporal demographic responses in the
      drier Kimberley region compared to the more mesic and consistently suitable Top
      End. We hypothesize that, in general, the effects of species' traits on
      sensitivity to climate fluctuation will be more evident in climatically marginal
      regions. If true, this points to the need in climatically marginal areas to craft
      more species-(or trait)-specific strategies for persistence under future climate
      change.

PMID- 29178446
TI  - Experimental and Theoretical Study of Enhanced Photocatalytic Activity of Mg
      Doped ZnO NPs and ZnO/rGO Nanocomposites.
AB  - A systematic experimental and theoretical study of the origin of the enhanced
      photocatalytic performance of Mg-doped ZnO nanoparticles (NPs) and Mg-doped
      ZnO/reduced graphene oxide (rGO) nanocomposites has been performed. In addition
      to Mg, Cd was chosen as a doping material for the bandgap engineering of ZnO NPs,
      and its effects were compared with that of Mg in the photocatalytic performance
      of ZnO nanostructures. The experimental results revealed that Mg, as a doping
      material, recognizably ameliorates the photocatalytic performance of ZnO NPs and
      ZnO/graphene nanocomposites. Transmission electron microscopy (TEM) images showed
      that the Mg-doped and Cd-doped ZnO NPs had the same size. The optical properties
      of the samples indicated that Cd narrowed the bandgap, whereas Mg widened the
      bandgap of the ZnO NPs and the oxygen vacancy concentration was similar for both
      samples. Based on the experimental results, the narrowing of the bandgap, the
      particle size, and the oxygen vacancy did not enhance the photocatalytic
      performance. However, Brunauer-Emmett-Teller (BET) and Barret-Joyner-Halenda
      (BJH) models showed that Mg caused increased textural properties of the samples,
      whereas rGO played an opposite role. A theoretical study, conducted by using DFT
      methods, showed that the improvement in the photocatalytic performance of Mg
      doped ZnO NPs was due to a higher electron transfer from the Mg-doped ZnO NPs to
      the dye molecules compared with pristine ZnO and Cd-doped ZnO NPs. Moreover,
      according to the experimental results, along with Mg, graphene also played an
      important role in the photocatalytic performance of ZnO.

PMID- 29178443
TI  - Review: The past, present and future challenges in epilepsy-related and sudden
      deaths and biobanking.
AB  - Awareness and research on epilepsy-related deaths (ERD), in particular Sudden
      Unexpected Death in Epilepsy (SUDEP), have exponentially increased over the last
      two decades. Most publications have focused on guidelines that inform clinicians
      dealing with these deaths, educating patients, potential risk factors and
      mechanisms. There is a relative paucity of information available for pathologists
      who conduct these autopsies regarding appropriate post mortem practice and
      investigations. As we move from recognizing SUDEP as the most common form of ERD
      toward in-depth investigations into its causes and prevention, health
      professionals involved with these autopsies and post mortem procedure must remain
      fully informed. Systematizing a more comprehensive and consistent practice of
      examining these cases will facilitate (i) more precise determination of cause of
      death, (ii) identification of SUDEP for improved epidemiological surveillance
      (the first step for an intervention study), and (iii) biobanking and cell-based
      research. This article reviews how pathologists and healthcare professionals have
      approached ERD, current practices, logistical problems and areas to improve and
      harmonize. The main neuropathology, cardiac and genetic findings in SUDEP are
      outlined, providing a framework for best practices, integration of clinical,
      pathological and molecular genetic investigations in SUDEP, and ultimately
      prevention.

PMID- 29178448
TI  - Expanding the Clinical Spectrum of Phenotypes Caused by Pathogenic Variants in
      PLOD2.
AB  - Osteogenesis imperfecta (OI) is a strikingly heterogeneous group of disorders
      with a broad range of phenotypic variations. It is also one of the differential
      diagnoses in bent bone dysplasias along with campomelic dysplasia and
      thanatophoric dysplasia and can usually be distinguished by decreased bone
      mineralization and bone fractures. Bent bone dysplasias also include syndromes
      such as kyphomelic dysplasia (MIM:211350) and mesomelic dysplasia Kozlowski
      Reardon (MIM249710), both of which have been under debate regarding whether or
      not they are a real entity or simply a phenotypic manifestation of another
      dysplasia including OI. Bruck syndrome type 2 (BRKS2; MIM:609220) is a rare form
      of autosomal recessive OI caused by biallelic PLOD2 variants and is associated
      with congenital joint contractures with pterygia. In this report, we present six
      patients from four families with novel PLOD2 variants. All cases had multiple
      fractures. Other features ranged from prenatal lethal severe angulation of the
      long bones as in kyphomelic dysplasia and mesomelic dysplasia Kozlowski-Reardon
      through classical Bruck syndrome to moderate OI with normal joints. Two siblings
      with a kyphomelic dysplasia-like phenotype who were stillborn had compound
      heterozygous variants in PLOD2 (p.Asp585Val and p.Ser166*). One infant who
      succumbed at age 4 months had a bent bone phenotype phenotypically like skeletal
      dysplasia Kozlowski-Reardon (with mesomelic shortening, camptodactyly,
      retrognathia, cleft palate, skin dimples, but also with fractures). He was
      homozygous for the nonsense variant (p.Trp561*). Two siblings had various degrees
      of Bruck syndrome caused by the homozygous missense variant, p.His687Arg.
      Furthermore a boy with a clinical presentation of moderate OI had a possibly
      pathogenic homozygous variant p.Trp588Cys. Our experience of six patients with
      biallelic pathogenic variants in PLOD2 expands the phenotypic spectrum in the
      PLOD2-related phenotypes. (c) 2017 American Society for Bone and Mineral
      Research.

PMID- 29178449
TI  - Reply.

PMID- 29178447
TI  - Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE
      syndrome.
AB  - CHARGE syndrome (CS) is a genetic disorder whose first description included
      Coloboma, Heart disease, Atresia of choanae, Retarded growth and development,
      Genital hypoplasia, and Ear anomalies and deafness, most often caused by a
      genetic mutation in the CHD7 gene. Two features were then added: semicircular
      canal anomalies and arhinencephaly/olfactory bulb agenesis, with classification
      of typical, partial, or atypical forms on the basis of major and minor clinical
      criteria. The detection rate of a pathogenic variant in the CHD7 gene varies from
      67% to 90%. To try to have an overview of this heterogenous clinical condition
      and specify a genotype-phenotype relation, we conducted a national study of
      phenotype and genotype in 119 patients with CS. Selected clinical diagnostic
      criteria were from Verloes (2005), updated by Blake & Prasad (). Besides
      obtaining a detailed clinical description, when possible, patients underwent a
      full ophthalmologic examination, audiometry, temporal bone CT scan, gonadotropin
      analysis, and olfactory-bulb MRI. All patients underwent CHD7 sequencing and MLPA
      analysis. We found a pathogenic CHD7 variant in 83% of typical CS cases and 58%
      of atypical cases. Pathogenic variants in the CHD7 gene were classified by the
      expected impact on the protein. In all, 90% of patients had a typical form of CS
      and 10% an atypical form. The most frequent features were deafness/semicircular
      canal hypoplasia (94%), pituitary defect/hypogonadism (89%), external ear
      anomalies (87%), square-shaped face (81%), and arhinencephaly/anosmia (80%).
      Coloboma (73%), heart defects (65%), and choanal atresia (43%) were less
      frequent.

PMID- 29178450
TI  - Generic approach to the method development of intact protein separations using
      hydrophobic interaction chromatography.
AB  - We describe a liquid chromatography method development approach for the
      separation of intact proteins using hydrophobic interaction chromatography.
      First, protein retention was determined as function of the salt concentration by
      isocratic measurements and modeled using linear regression. The error between
      measured and predicted retention factors was studied while varying gradient time
      (between 15 and 120 min) and gradient starting conditions, and ranged between 2
      and 15%. To reduce the time needed to develop optimized gradient methods for
      hydrophobic interaction chromatography separations, retention-time estimations
      were also assessed based on two gradient scouting runs, resulting in
      significantly improved retention-time predictions (average error < 2.5%) when
      varying gradient time. When starting the scouting gradient at lower salt
      concentrations (stronger eluent), retention time prediction became inaccurate in
      contrast to predictions based on isocratic runs. Application of three scouting
      runs and a nonlinear model, incorporating the effects of gradient duration and
      mobile-phase composition at the start of the gradient, provides accurate results
      (improved fitting compared to the linear solvent-strength model) with an average
      error of 1.0% and maximum deviation of -8.3%. Finally, gradient scouting runs and
      retention-time modeling have been applied for the optimization of a critical-pair
      protein isoform separation encountered in a biotechnological sample.

PMID- 29178452
TI  - Insane Sex Offenders: Psychiatric and Legal Characteristics of Sexual Offenders
      Found Not Guilty by Reason of Insanity.
AB  - There is little known about sexual offenders hospitalized under forensic
      commitment statutes such as not guilty by reason of insanity (NGRI). We conducted
      a chart review to delineate the demographic, clinical, and legal characteristics
      of NGRI sexual offenders (n = 68) committed to the California Department of State
      Hospitals-Napa, including 41 found NGRI for a sexual offense and 27 found NGRI
      for a nonsexual offense. The two groups did not differ significantly in their
      demographics, psychiatric diagnoses, victim characteristics, or recidivism risk
      as measured by the Static-99R. Those found NGRI for a sexual offense were older
      at the time of their first criminal and first violent offense, younger at the
      time of their committing offense, and had fewer prior total convictions and
      sexual offense convictions. These findings may indicate that sexual offenders
      found NGRI for a sexual offense are less antisocial than those found NGRI for a
      nonsexual offense.

PMID- 29178451
TI  - Using imputed genotype data in the joint score tests for genetic association and
      gene-environment interactions in case-control studies.
AB  - Genome-wide association studies (GWAS) are now routinely imputed for untyped
      single nucleotide polymorphisms (SNPs) based on various powerful statistical
      algorithms for imputation trained on reference datasets. The use of predicted
      allele counts for imputed SNPs as the dosage variable is known to produce valid
      score test for genetic association. In this paper, we investigate how to best
      handle imputed SNPs in various modern complex tests for genetic associations
      incorporating gene-environment interactions. We focus on case-control association
      studies where inference for an underlying logistic regression model can be
      performed using alternative methods that rely on varying degree on an assumption
      of gene-environment independence in the underlying population. As increasingly
      large-scale GWAS are being performed through consortia effort where it is
      preferable to share only summary-level information across studies, we also
      describe simple mechanisms for implementing score tests based on standard meta
      analysis of "one-step" maximum-likelihood estimates across studies. Applications
      of the methods in simulation studies and a dataset from GWAS of lung cancer
      illustrate ability of the proposed methods to maintain type-I error rates for the
      underlying testing procedures. For analysis of imputed SNPs, similar to typed
      SNPs, the retrospective methods can lead to considerable efficiency gain for
      modeling of gene-environment interactions under the assumption of gene
      environment independence. Methods are made available for public use through CGEN
      R software package.

PMID- 29178453
TI  - Effects of circulating member B of the family with sequence similarity 3 on the
      risk of developing metabolic syndrome and its components: A 5-year prospective
      study.
AB  - AIMS/INTRODUCTION: Member B of the family with sequence similarity 3 (FAM3B),
      also known as pancreatic-derived factor, is mainly synthesized and secreted by
      islet beta-cells, and plays a role in abnormal metabolism of glucose and lipids.
      However, the prospective association of FAM3B with metabolic disorders remains
      unclear. The present study aimed to reveal the predictive relationship between
      pancreas-specific cytokine and metabolic syndrome (MetS). MATERIALS AND METHODS:
      A total of 210 adults (88 men and 122 women) without MetS, aged between 40 and 65
      years, were recruited and received a comprehensive health examination. Baseline
      serum FAM3B levels were determined by sandwich enzyme-linked immunosorbent assay.
      Subsequently, all participants underwent a follow-up examination after 5 years.
      MetS was identified in accordance with the International Diabetes Federation
      criteria. RESULTS: During follow up, 35.7% participants developed MetS. In
      comparison with the non-MetS group, participants with MetS had an increased serum
      FAM3B at baseline (21.85 ng/mL [19.38, 24.17 ng/mL] vs 28.56 ng/mL [25.32, 38.10
      ng/mL], P < 0.001). Moreover, serum FAM3B was significantly associated with
      variations in fasting plasma insulin (r = -0.306, P < 0.001), homeostasis model
      assessment of beta-cell function (r = -0.328, P < 0.001) and homeostasis model
      assessment of insulin resistance (r = -0.191, P = 0.006). Furthermore, a positive
      correlation between baseline FAM3B and the incidence of MetS was observed, even
      after multivariable adjustment (relative risk 1.23 [1.15, 1.31], P < 0.001).
      Furthermore, the optimal cut-off values of FAM3B was 23.98 ng/mL for predicting
      MetS based on the Youden Index. CONCLUSIONS: Elevated circulating FAM3B might be
      considered as a predictor of newly-onset MetS and its progression.

PMID- 29178454
TI  - l-Cysteine-modified silver-functionalized silica-based material as an efficient
      solid-phase extraction adsorbent for the determination of bisphenol A.
AB  - A new silver-functionalized silica-based material with a core-shell structure
      based on silver nanoparticle-coated silica spheres was synthesized, and silver
      nanoparticles were modified using strongly bound l-cysteine. l-Cysteine
      silver@silica was characterized by scanning electron microscopy and FTIR
      spectroscopy. Then, a solid-phase extraction method based on l-cysteine
      silver@silica was developed and successfully used for bisphenol A determination
      prior to HPLC analysis. The results showed that the l-cysteine-silver@silica as
      an adsorbent exhibited good enrichment capability for bisphenol A, and the
      maximum adsorption saturation was 20.93 mg/g. Moreover, a short adsorption
      equilibrium time was obtained due to the presence of silver nanoparticles on the
      surface of the silica. The extraction efficiencies were then optimized by varying
      the eluents and pH. Under the optimized conditions, good linearity for bisphenol
      A was obtained in the range from 0.4 to 4.0 MUM (R2  > 0.99) with a low limit of
      detection (1.15 ng/mL). The spiked recoveries from tap water and milk samples
      were satisfactory (85-102%) with relative standard deviations below 5.2% (n = 3),
      which indicated that the method was suitable for the analysis of bisphenol A in
      complex samples.

PMID- 29178455
TI  - @AACAnatomy twitter account goes live: A sustainable social media model for
      professional societies.
AB  - Social media, with its capabilities of fast, global information sharing, provides
      a useful medium for professional development, connecting and collaborating with
      peers, and outreach. The goals of this study were to describe a new, sustainable
      model for Twitter use by professional societies, and analyze its impact on
      @AACAnatomy, the Twitter account of the American Association of Clinical
      Anatomists. Under supervision of an Association committee member, an anatomy
      graduate student developed a protocol for publishing daily tweets for
      @AACAnatomy. Five tweet categories were used: Research, Announcements, Replies,
      Engagement, and Community. Analytics from the 6-month pilot phase were used to
      assess the impact of the new model. @AACAnatomy had a steady average growth of 33
      new followers per month, with less than 10% likely representing Association
      members. Research tweets, based on Clinical Anatomy articles with an abstract
      link, were the most shared, averaging 5,451 impressions, 31 link clicks, and nine
      #ClinAnat hashtag clicks per month. However, tweets from non-Research categories
      accounted for the highest impression and engagement metrics in four out of six
      months. For all tweet categories, monthly averages show consistent interaction of
      followers with the account. Daily tweet publication resulted in a 103% follower
      increase. An active Twitter account successfully facilitated regular engagement
      with @AACAnatomy followers and the promotion of clinical anatomy topics within a
      broad community. This Twitter model has the potential for implementation by other
      societies as a sustainable medium for outreach, networking, collaboration, and
      member engagement. Clin. Anat. 31:566-575, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178456
TI  - Oral health-related behaviours do not mediate the effect of maternal education on
      adolescents' gingival bleeding: A birth cohort study.
AB  - OBJECTIVES: To test whether maternal education has a direct effect on gingival
      bleeding in adolescents aged 12 and to assess whether oral health behaviours over
      time mediate that association. METHODS: Two oral health studies nested in the
      1993 Pelotas (Brazil) birth cohort study were carried out in participants aged 6
      (n = 359) and 12 years (n = 339). The proportion of teeth with bleeding on
      probing (BOP) and the median number of teeth with gingivitis at age 12 were
      recorded. Maternal education at birth was the exposure. Toothbrushing frequency
      and dental visit at ages 6 and 12 years were investigated as mediators of the
      association between maternal education at birth and gingival bleeding. Time
      varying family income through childhood and adolescence was included as later
      confounder. Paternal education was taken as baseline confounder. The controlled
      direct effect (CDE) of maternal education at child's birth on gingival bleeding
      at age 12 was estimated using marginal structural models (MSM). Additionally,
      path analysis was employed to estimate standardized direct, indirect and total
      effects of maternal education at birth on gingival bleeding. RESULTS: Adjusted
      analyses using MSM showed that adolescents whose mothers had <8 years of
      education had 3.82 higher risk of having teeth with gingival bleeding above the
      median (rate ratio RR 3.82; 95% CI: 1.68-8.19). Low maternal education doubled
      the proportion of gingival bleeding at age 12 not mediated by dental visit and
      toothbrushing frequency (RR 1.99; 95% CI: 1.52-2.60). Path analysis revealed that
      maternal education had a direct effect on gingival bleeding independently of the
      mediators. CONCLUSIONS: The pattern of oral health behaviours does not explain
      the association between mother's education and adolescent's gingival bleeding.
      Individual-based approaches focused on oral health-related behaviours tend to
      fail to prevent gingival bleeding.

PMID- 29178457
TI  - Relative dosimetry with an MR-linac: Response of ion chambers, diamond, and diode
      detectors for off-axis, depth dose, and output factor measurements.
AB  - PURPOSE: The purpose of this study was to acquire beam data for an MR-linac, with
      and without a 1.5 T magnetic field, by using a variety of commercially available
      detectors to assess their relative response in the magnetic field. The impact of
      the magnetic field on the measured dose distribution was also assessed. METHODS:
      An MR-safe 3D scanning water phantom was used to measure output factors, depth
      dose curves, and off-axis profiles for various depths and for field sizes between
      2 * 2 cm2 and 22 * 22 cm2 for an Elekta MR-linac beam with the orthogonal 1.5 T
      magnetic field on or off. An on-board MV portal imaging system was used to ensure
      that the reproducibility of the detector position, both with and without the
      magnetic field, was within 0.1 mm. The detectors used included ionization
      chambers with large, medium, and small sensitive volumes; a diamond detector; a
      shielded diode; and an unshielded diode. RESULTS: The offset of the effective
      point of measurement of the ionization chambers was found to be reduced by at
      least half for each chamber in the direction parallel with the beam. A lateral
      shift of similar magnitude was also introduced to the chambers' effective point
      of measurement toward the average direction of the Lorentz force. A similar
      lateral shift (but in the opposite direction) was also observed for the diamond
      and diode detectors. The measured lateral shift in the dose distribution was
      independent of depth and field size for each detector for fields between 2 * 2
      cm2 and 10 * 10 cm2 . The shielded diode significantly misrepresented the dose
      distribution in the lateral direction perpendicular to the magnetic field, making
      it seem more symmetric. The percentage depth dose was generally found to be lower
      with the magnetic field than without, but this difference was reduced as field
      size increased. The depth of maximum dose showed little dependence on field size
      in the presence of the magnetic field, with values from 1.2 cm to 1.3 cm between
      the 2 * 2 cm2 and 22 * 22 cm2 fields. Output factors measured in the magnetic
      field at the center of the beam profile produced a larger spread of values
      between detectors for fields smaller than 10 * 10 cm2 (with a spread of 2% at 3 *
      3 cm2 ). The spread of values was more consistent when the output factors were
      measured at the point of peak intensity of the lateral dose distribution instead
      (except for the shielded diode which differed by up to 2% depending on field
      size). CONCLUSIONS: The magnetic field of the MR-linac alters the effective point
      of measurement of ionization chambers, shifting it both downstream and laterally.
      Shielded diodes produce incorrect and misleading dose profiles. The output factor
      measured at the point of peak intensity in the lateral dose distribution is more
      robust than the conventional output factor (measured at central axis). Diodes are
      not recommended for output factor measurements in the magnetic field.

PMID- 29178459
TI  - Inflammatory and metabolic responses to an intramammary lipopolysaccharide
      challenge in early lactating cows supplemented with conjugated linoleic acid.
AB  - Supplementation of dairy cows with trans-10, cis-12 conjugated linoleic acid
      (CLA) allows nutrient repartitioning despite an energy deficiency in early
      lactation, which might be a benefit for the immune system, too. In this study, we
      investigated potential nutrient sparing effects of CLA in early lactating cows
      with low plasma glucose concentrations exposed to an intramammary
      lipopolysaccharide (LPS) challenge. Fifteen multiparous Holstein cows were
      exposed to an intramammary LPS challenge in week 4 p.p. Eight cows (CLA) were
      supplemented daily with 70 g of lipid-encapsulated CLA (6.8 g trans-10, cis-12
      and 6.6 g of the cis-9, trans-11 CLA isomer; CLA) and seven cows with 56 g of
      control fat (CON). Blood samples were obtained every 30 min along with rectal
      temperature, heart and respiratory rate, and milk samples were taken hourly until
      10 hr after the LPS application. Plasma was analysed for concentrations of
      glucose, free fatty acids, beta-hydroxybutyrate (BHB), cortisol, insulin and
      glucagon. In milk, somatic cell count and activity of lactate dehydrogenase were
      determined. Initial plasma glucose concentration was lower in CLA than in CON.
      During the immunostimulation, CLA had higher glucose concentrations than CON, and
      BHB decreased distinctly in CLA, whereas CON cows maintained BHB concentration at
      a lower level. Body temperature in CLA increased earlier, the difference between
      peak and basal temperature was higher, and the decline thereafter occurred
      earlier. In conclusion, CLA supplementation of early lactating cows exposed to an
      intramammary LPS challenge affected local and systemic immune responses. We
      assume that CLA supplementation triggered glycogen storage. Cows supplemented
      with CLA provided more glucose and preferentially used BHB as an energy source
      during the immune response. The more intense metabolic and more concentrated
      endocrine responses support an immunomodulatory effect of CLA supplementation.

PMID- 29178458
TI  - Impairment of Bone Remodeling in LIGHT/TNFSF14-Deficient Mice.
AB  - Multiple cytokines produced by immune cells induce remodeling and aid in
      maintaining bone homeostasis through differentiation of bone-forming osteoblasts
      and bone-resorbing osteoclasts. Here, we investigate bone remodeling controlled
      by the tumor necrosis factor (TNF) superfamily cytokine LIGHT. LIGHT-deficient
      mice (Tnfsf14-/- ) exhibit spine deformity and reduced femoral cancellous bone
      mass associated with an increase in the osteoclast number and a slight decrease
      of osteoblasts compared with WT mice. The effect of LIGHT in bone cells can be
      direct or indirect, mediated by both the low expression of the anti
      osteoclastogenic osteoprotegerin (OPG) in B and T cells and reduced levels of the
      pro-osteoblastogenic Wnt10b in CD8+ T cells in Tnfsf14-/- mice. LIGHT stimulation
      increases OPG levels in B, CD8+ T, and osteoblastic cells, as well as Wnt10b
      expression in CD8+ T cells. The high bone mass in Light and T- and B-cell
      deficient mice (Rag- /Tnfsf14- ) supports the cooperative role of the immune
      system in bone homeostasis. These results implicate LIGHT as a potential target
      in bone disease. (c) 2017 American Society for Bone and Mineral Research.

PMID- 29178460
TI  - The adequate rocuronium dose required for complete block of the adductor muscles
      of the thigh.
AB  - BACKGROUND: Rocuronium can prevent the obturator jerk during transurethral
      resection of bladder tumors. We investigated the adequate rocuronium dose
      required for complete block of the thigh adductor muscles, and its correlation
      with individual responses of the adductor pollicis muscle to rocuronium. METHODS:
      Eleven patients scheduled for transurethral resection of bladder tumors under
      general anesthesia were investigated. After general anesthesia induction,
      neuromuscular monitoring of the adductor pollicis muscle and ultrasonography
      guided stimulation of the obturator nerve was commenced. Rocuronium, 0.15 mg/kg,
      was repeatedly administered intravenously. The adequate rocuronium dose required
      for complete block of the thigh muscles, defined as the cumulative dose of
      rocuronium administered until that time, and its correlation with the first
      twitch response of the adductor pollicis muscle on train-of-four stimulation
      after initial rocuronium administration was analyzed. RESULTS: The rocuronium
      dose found adequate for complete block of the thigh muscles was 0.30 mg/kg in
      seven patients and 0.45 mg/kg in the remaining four patients, which did not
      correlate with the first twitch response. At the time of complete block of the
      thigh muscles, the neuromuscular blockade level of the adductor pollicis muscle
      varied greatly, although the level was never more profound than a post-tetanic
      count of 1. CONCLUSION: Although the response of the adductor pollicis muscle to
      rocuronium cannot be used to determine the adequate rocuronium dose required for
      complete block of the thigh muscles, intense blockade, with maintenance of post
      tetanic count at <= 1 in the adductor pollicis muscle is essential to prevent the
      obturator jerk.

PMID- 29178461
TI  - The guardian of the genome p53 regulates exercise-induced mitochondrial
      plasticity beyond organelle biogenesis.
AB  - The Guardian of the Genome p53 has been established as a potent tumour
      suppressor. However, culminating from seminal findings in rodents more than a
      decade ago, several studies have demonstrated that p53 is required to maintain
      basal mitochondrial function [ie, respiration and reactive oxygen species (ROS)
      homeostasis]. Specifically, via its role(s) as a tumour suppressor, p53
      intimately surveys cellular DNA damage, in particular mitochondrial DNA (mtDNA),
      to ensure that the mitochondrial network is carefully monitored and cell
      viability is upheld, because aberrant mtDNA damage leads to apoptosis and
      widespread cellular perturbations. Indeed, data from rodents and humans have
      demonstrated that p53 forms an integral component of the exercise-induced signal
      transduction network regulating skeletal muscle mitochondrial remodelling. In
      response to exercise-induced disruptions to cellular homeostasis that have the
      potential to harm mtDNA (eg, contraction-stimulated ROS emissions), appropriate
      p53-regulated, mitochondrial turnover responses prevail to protect the genome and
      ultimately facilitate a shift from aerobic glycolysis to oxidative
      phosphorylation, adaptations critical for endurance-based exercise that are
      commensurate with p53's role as a tumour suppressor. Despite these observations,
      several discrepancies exist between rodent and human studies pinpointing p53
      subcellular trafficking from nuclear-to-mitochondrial compartments following
      acute exercise. Such interspecies differences in p53 activity and the plausible
      p53-mediated adaptations to chronic exercise training will be discussed herein.

PMID- 29178462
TI  - Role of dexamethasone in the long-term functional maturation of MSC-laden
      hyaluronic acid hydrogels for cartilage tissue engineering.
AB  - The purpose of study was to investigate the maturation of mesenchymal stem cells
      (MSC) laden in HA constructs with various combinations of chemically defined
      medium (CM) components and determine the impact of dexamethasone and serum on
      construct properties. Constructs were cultured in CM with the addition or
      withdrawal of media components or were transferred to serum containing media that
      partially represents an in vivo-like condition where pro-inflammatory signals are
      present. Constructs cultured in CM+ (CM with TGF-beta3) and DEX- (CM+ without
      dexamethasone) conditions produced robust matrix, while those in ITS/BSA/LA- (CM+
      without ITS/BSA/LA) and Serum+ (10% FBS with TGF-beta3) produced little matrix.
      While construct properties in DEX- were greater than those in CM+ at 4 weeks,
      properties in CM+ and DEX- reversed by 8 weeks. While construct properties in DEX
      were greater than those in CM+ at 4 weeks, the continued absence or removal of
      dexamethasone resulted in marked GAG loss by 8 weeks. Conversely, the continued
      presence or new addition of dexamethasone at 4 weeks further improved or
      maintained construct properties through 8 weeks. Finally, when constructs were
      converted to Serum (in the continued presence of TGF-beta3 with or without
      dexamethasone) after pre-culture in CM+ for 4 weeks, GAG loss was attenuated with
      addition of dexamethasone. Interestingly, however, collagen content and type was
      not impacted. In conclusion, dexamethasone influences the functional maturation
      of MSC-laden HA constructs, and may help to maintain properties during long-term
      culture or with in vivo translation by repressing pro-inflammatory signals. (c)
      2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res 36:1717-1727, 2018.

PMID- 29178463
TI  - Psychotic (delusional) depression and suicidal attempts: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: It still remains unclear whether psychotic features increase the risk
      of suicidal attempts in major depressive disorder. Thus, we attempted, through a
      systematic review coupled with a meta-analysis, to elucidate further whether
      unipolar psychotic depression (PMD) compared to non-PMD presents higher levels of
      suicidal attempts. METHOD: A systematic search was conducted in PubMed, EMBASE,
      PsycINFO as well as in various databases of the so-called gray literature for all
      studies providing data on suicidal attempts in PMD compared to non-PMD, and the
      results were then subjected to meta-analysis. RESULTS: Twenty studies met our
      inclusion criteria, including in total 1,275 PMD patients and 5,761 non-PMD
      patients. An elevated risk for suicide attempt for PMD compared to non-PMD
      patients was found: The total (lifetime) fixed-effects pooled OR was 2.11 (95%
      CI: 1.81-2.47), and the fixed-effects pooled OR of the five studies of the acute
      phase of the disorder was 1.93 (95% CI: 1.33-2.80). This elevated risk of
      suicidal attempt for PMD patients remained stable across all age groups of adult
      patients. CONCLUSION: Despite data inconsistency and clinical heterogeneity, this
      systematic review and meta-analysis showed that patients with PMD are at a two
      fold higher risk, both during lifetime and in acute phase, of committing a
      suicidal attempt than patients with non-PMD.

PMID- 29178464
TI  - Perceptions and opinions of pet owners in the United Sates about surgery, pain
      management, and anesthesia in dogs and cats.
AB  - OBJECTIVE: To evaluate pet owners' perceptions and understanding of surgical
      pain, perioperative pain management, and anesthesia. STUDY DESIGN: Prospective
      owner survey. SAMPLE POPULATION: Eight veterinary hospitals each provided 200
      surveys for distribution to pet owners. METHODS: A survey evaluated owners'
      perceptions and opinions related to surgical pain, perioperative pain management,
      anesthesia in dogs and cats, and owner demographics (sex, age, education,
      employment, previous surgical experience, and pet ownership) in 8 regions of the
      United States (Alaska, Florida, Hawaii, Massachusetts, Oregon, Ohio, Texas,
      Washington, DC). Effects of demographics on survey questions were analyzed by
      using a Cochran-Mantel-Haenszel test. Descriptive statistics and frequency
      distributions were calculated when applicable. RESULTS: 948/1600 (59.25%) of
      distributed questionnaires were completed. Owners reported that analgesics were
      "always needed" more often for surgical procedures than medical conditions.
      Knowing what to expect during recovery (99%), being informed of procedures and
      risks (98%), adequate pain management (98%), and having a board-certified
      anesthesiologist perform anesthesia (94%) were considered "important" or "very
      important" by owners. The majority of owners agreed that pain affects quality of
      life (81%), interactions with family and pets (73%), and that declawing is a
      painful procedure (59%). Older respondents (>46 years), women, owners who have
      had previous surgery or who have pets that have had previous surgery, and those
      in health care professions have a better understanding of pain but also expect
      effective client communication. CONCLUSION: Improving our understanding of pet
      owners' perceptions and knowledge related to anesthesia, surgery, and pain may
      lead to improved client education, satisfaction, and compliance with
      administration of analgesics.

PMID- 29178465
TI  - Detection of human immunodeficiency virus, hepatitis C virus, and hepatitis B
      virus in postmortem blood specimens using infectious disease assays licensed for
      cadaveric donor screening.
AB  - BACKGROUND: Evaluation of assay performance on postmortem blood specimens
      (obtained after cessation of the heartbeat) presents unique scientific and
      regulatory challenges. In the United States, assay performance is evaluated in
      part by spiking postmortem specimens. METHODS: Fifty-four specimens obtained from
      decedents known to be infected with human immunodeficiency virus (HIV), hepatitis
      C virus (HCV), or hepatitis B virus (HBV), including some coinfections, were
      tested for each virus using Food and Drug Administration (FDA)-licensed donor
      screening tests for nucleic acid, antibody, and antigen. RESULTS: For each
      disease, >95% of subjects who were reported to have an infection at the time of
      death had a positive test result on at least one of the donor screening assays
      for that infection. CONCLUSION: Licensed donor screening tests were positive on
      postmortem specimens obtained within 24 hours of death from individuals dying
      with HIV, HCV, and/or HBV, and were able to detect presence of the virus. The use
      of multiple tests (including antibody and direct viral detection methods) is
      necessary to adequately evaluate donors.

PMID- 29178466
TI  - An approach to discussing personal and social identity terminology with patients.
AB  - As the United States of America becomes more socially diverse, it is more
      important now than ever for health care providers to become more aware of their
      patients' social identities. It is imperative that providers engage with their
      patients and see how each of them identifies personally in relation to social
      construction terminology. As with the terminology of human anatomy, there is a
      vast and diverse vocabulary concerning the anatomy of society, which is also
      clinically relevant to health care providers. If health care providers take the
      initiative to discuss how their patients identify, they can understand better how
      those patients experience the world, and this can significantly affect many
      facets of their health and health care experience. Giving respect fosters the
      creation of a strong relationship within which patients can share very personal
      and intimate information, which in turn allows health care providers the
      possibility of providing the best healthcare. This discussion will build upon and
      integrate current academic research and opinion for tangible clinical use while
      discussing various social and personal identities, including but not limited to
      race, gender, gender expression, sex, sexual orientation, religion, ethnicity,
      socioeconomic class, and physical and mental abilities. Clin. Anat. 31:136-139,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178467
TI  - Tunable Performance of Manganese Oxide Nanostructures as MRI Contrast Agents.
AB  - The development of responsive magnetic resonance imaging contrast agents opens
      the door to a highly sensitive and specific diagnosis of altered physiological
      conditions. In this field, manganese dioxide (MnO2 ) is starting to be a leading
      contributor due to its susceptibility to conditions relevant to human diseased
      states, such as cancer. So far, the preclinical application of MnO2 has mainly
      been in the form of nanosheets, with enhancements of magnetic resonance imaging
      signals up to 50-fold upon activation. Herein, we thoroughly investigate, through
      a simple reaction, a series of Mnx Oy samples and correlate their phase
      composition and structure/morphology to the performance as classic/responsive MRI
      contrast agents in response to redox changes. Signal enhancements as high as 140
      fold were obtained from MnO2 nano-urchins, and their capability as responsive
      magnetic resonance imaging contrast agents was demonstrated in vitro.

PMID- 29178468
TI  - DFT calculations of the defect structures, electronic structures, and EPR
      parameters for three Rh2+ centers in AgCl.
AB  - The local structures for various Rh2+ centers in AgCl are theoretically studied
      using density functional theory (DFT) with periodic CP2K program. Through
      geometry optimizing, the stable ground states with minimal energies and
      electronic structures are obtained for the tetragonally elongated (TE ),
      orthorhombically elongated (OE ), and tetragonally compressed (TC ) centers, and
      the corresponding g and hyperfine coupling tensors are calculated in ORCA level.
      The calculations reveal obvious Jahn-Teller elongation distortions of about 0.109
      and 0.110 A along [001] axis for TE and OE centers without and with 1 next
      nearest neighbor (nnn) cation vacancy VAg in [100] axis, respectively. Whereas TC
      center with 1 nnn VAg along [001] axis exhibits moderate axial compression of
      about 0.066 A due to the Jahn-Teller effect. For OE and TC centers with 1 nnn VAg
      , the ligand intervening in the central Rh2+ and the VAg is found to displace
      away from the VAg by about 0.028 and 0.024 A, respectively. The present results
      are discussed and compared with those of the previous calculations based on the
      perturbation formulas by using the improved ligand field theory.

PMID- 29178469
TI  - Multiracial in Middle School: The Influence of Classmates and Friends on Changes
      in Racial Self-Identification.
AB  - In the present research, the influence of racial diversity among classmates and
      friends on changes in racial self-identification among multiracial youth was
      examined (n = 5,209; Mage  = 10.56 years at the beginning of sixth grade). A
      novel individual-level measure of diversity among classmates based on
      participants' course schedules was utilized. The findings revealed that although
      there was some fluidity in multiracial identification at the beginning of middle
      school, changes in multiracial identification were more evident later in middle
      school. In addition, although diversity among classmates and friends both
      increased the likelihood of multiracial identification in the beginning of middle
      school, only diversity among friends mattered later in middle school, when
      fluidity in multiracial identification was at its peak.

PMID- 29178470
TI  - Lymphocyte-independent pathways underlie the pathogenesis of murine
      cytomegalovirus-associated secondary haemophagocytic lymphohistiocytosis.
AB  - Haemophagocytic lymphohistiocytosis (HLH) constitutes a spectrum of immunological
      disorders characterized by uncontrolled immune activation and key symptoms such
      as fever, splenomegaly, pancytopenia, haemophagocytosis, hyperferritinaemia and
      hepatitis. In genetic or primary HLH, hyperactivated CD8+ T cells are the main
      drivers of pathology. However, in acquired secondary HLH, the role of lymphocytes
      remains vague. In the present study the involvement of lymphocytes in the
      pathogenesis of a cytomegalovirus-induced model of secondary HLH was explored. We
      have previously reported CD8+ T cells to be redundant in this model, and
      therefore focused on CD4+ helper and regulatory T cells. CD4+ T cells were
      activated markedly and skewed towards a proinflammatory T helper type 1
      transcription profile in mice displaying a severe and complete HLH phenotype.
      Counter to expectations, regulatory T cells were not reduced in numbers and were,
      in fact, more activated. Therapeutic strategies targeting CD25high hyperactivated
      T cells were ineffective to alleviate disease, indicating that T cell
      hyperactivation is not a pathogenic factor in cytomegalovirus-induced murine HLH.
      Moreover, even though T cells were essential in controlling viral proliferation,
      CD4+ T cells, in addition to CD8+ T cells, were dispensable in the development of
      the HLH-like syndrome. In fact, no T or B cells were required for induction and
      propagation of HLH disease, as evidenced by the occurrence of cytomegalovirus
      associated HLH in severe combined immunodeficient (SCID) mice. These data suggest
      that lymphocyte-independent mechanisms can underlie virus-associated secondary
      HLH, accentuating a clear distinction with primary HLH.

PMID- 29178471
TI  - Methacholine challenge test: Comparison of tidal breathing and dosimeter methods
      in children.
AB  - INTRODUCTION: Methacholine Challenge Test (MCT) is used to confirm, assess the
      severity and/or rule out asthma. Two MCT methods are described as equivalent by
      the American Thoracic Society (ATS), the tidal breathing and the dosimeter
      methods. However, the majority of adult studies suggest that individuals with
      asthma do not react at the same PC20 between the two methods. Additionally, the
      nebulizers used are no longer available and studies suggest current nebulizers
      are not equivalent to these. Our study investigates the difference in positive
      MCT tests between three methods in a pediatric population. METHODS: A
      retrospective, chart review of all MCT performed with spirometry at the Montreal
      Children's Hospital from January 2006 to March 2016. A comparison of the
      percentage positive MCT tests with three methods, tidal breathing, APS dosimeter
      and dose adjusted DA-dosimeter, was performed at different cutoff points up to 8
      mg/mL. RESULTS: A total of 747 subjects performed the tidal breathing method, 920
      subjects the APS dosimeter method, and 200 subjects the DA-dosimeter method. At a
      PC20 cutoff <=4 mg/mL, the percentage positive MCT was significantly higher using
      the tidal breathing method (76.3%) compared to the APS dosimeter (45.1%) and DA
      dosimeter (65%) methods (P < 0.0001). CONCLUSION: The choice of nebulizer and
      technique significantly impacts the rate of positivity when using MCT to diagnose
      and assess asthma. Lack of direct comparison of techniques within the same
      individuals and clinical assessment should be addressed in future studies to
      standardize MCT methodology in children.

PMID- 29178472
TI  - Enzymatic degradation of hyaluronan hydrogels with different capacity for in situ
      bio-mineralization.
AB  - In situ cross-linked hyaluronan (HA) hydrogels with different capacities for
      biomineralization were prepared and their enzymatic degradation was monitored.
      Covalent incorporation of bisphosphonates (BPs) into HA hydrogel results in the
      increased stiffness of the hydrogel in comparison with the unmodified HA hydrogel
      of the same cross-linking density. The rate of enzymatic degradation of HABP
      hydrogel was significantly lower than the rate of degradation of control HA
      hydrogel in vitro. This effect is observed only in the presence of calcium ions
      that strongly bind to the matrix-anchored BP groups and promote further
      mineralization of the matrix. The degradation of the hydrogels was followed by
      noninvasive fluorescence measurements enabled after mild and chemoselective
      labeling of cross-linkable HA derivatives with a fluorescent tag.

PMID- 29178473
TI  - Thermochemistry of Substituted Benzamides and Substituted Benzoic Acids: Like
      Tree, Like Fruit?
AB  - Structure-property analyses of thermodynamic properties in chemical families of R
      substituted benzamides, R-substituted benzoic acids, as well as R-substituted
      benzenes have been performed. The general linear interrelations for the
      vaporization enthalpies and the gas-phase enthalpies of formation between the
      chemical families under study have been established. These linear correlations
      provide a simple method for prediction of thermodynamic properties for benzenes
      with various combination of R-group substituents on the benzene ring. In
      addition, the robust structure-property correlations revealed in this study can
      serve for the establishment of the internal consistency of experimental results
      available for each chemical series.

PMID- 29178474
TI  - In vivo Confocal Laser Microscopy for monitoring of actinic keratosis treatment:
      a comparison with histopathologic assessment after treatment with topical 5% 5
      fluorouracil.
AB  - BACKGROUND: Histological examination is the gold standard for actinic keratosis
      diagnosis; however, it is not always a feasible approach. Reflectance confocal
      microscopy (RCM) is a non-invasive technique that may be an alternative for
      monitoring actinic keratoses treatment response. Topical 5-fluorouracil is
      indicated for actinic keratosis multiple lesions and for field cancerization
      treatment. OBJECTIVES: To assess the RCM accuracy, sensibility and specificity
      for actinic keratosis, considering as a gold standard the histopathological
      examination; as well as to evaluate the efficacy of 5% 5-fluorouracil treatment.
      METHODS: This is a prospective study in actinic keratosis patients between August
      2014 and November 2015. RCM analyses were performed in one randomly selected
      actinic keratosis lesion of the upper limbs by two independent observers before
      and after 5% 5-fluorouracil treatment. At the end of treatment and with clinical
      bleaching of treated lesions, histological examination was performed by two
      pathologists. RESULTS: A total of 50 lesions were enroled, and 40 lesions
      presented complete clinical bleaching after treatment and were included in the
      final analysis. Accuracy, sensibility and specificity means among observers were
      83.8%, 84.6% and 83.3%, respectively. After 5-fluorouracil treatment, actinic
      keratosis was diagnosed in 45.0% (observer 1) and 32.5% (observer 2) of subjects
      according to RCM and in 32.5% of subjects according to histological examination.
      Considering RCM observers diagnosis, the concordance was substantial (k 0.637, P
      < 0.001). 5-fluorouracil led to a reduction in 55.0%-67.5% of actinic keratoses
      according to RCM analysis. CONCLUSION: This study allows to validate RCM as a non
      invasive method capable of monitoring actinic keratosis therapeutic response to 5
      fluorouracil, presenting efficacy comparable to histological examination.
      Additionally, the results suggest that 5-fluorouracil may be a satisfactory
      option for therapeutic control of this condition.

PMID- 29178475
TI  - Transcriptional analysis of the IL-33 receptor suppression of tumourigenicity 2
      and its effects on canine Type 2 T helper cells: a preliminary study.
AB  - BACKGROUND: Interleukin (IL)-33 has been implicated in the pathogenesis of canine
      atopic dermatitis, a Type 2 T helper cell (Th2)-associated disease. In humans, IL
      33 mediates its biological effects through the receptor suppression of
      tumourigenicity 2 (ST2), which is preferentially expressed on Th2 cells. The
      effects of IL-33 on canine Th2 cells are unclear. HYPOTHESIS/OBJECTIVES: ST2 may
      be preferentially expressed on canine Th2 cells; IL-33 may induce the
      transcription of Th2 cytokines from these cells. ANIMALS: Three healthy dogs were
      used. METHODS: The transcription level of st2 was quantified in helper T cells,
      cytotoxic T cells and Th2 cells isolated from healthy dogs. The transcription
      levels of Th2 cytokines including il-4, il-5, il-13 and il-31 were quantified in
      Th2 cells stimulated with recombinant canine (rc) IL-33 and/or recombinant human
      (rh) IL-2. RESULTS: Transcription of st2 was the strongest in Th2 cells. Th2
      cells also transcribed the genes for il-5 and il-13 after being stimulated with
      rcIL-33 and rhIL-2. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate
      that canine Th2 cells activated by IL-33 enhance Th2-mediated inflammation
      through the production of IL-5 and IL-13.

PMID- 29178476
TI  - A network of jasmonate-responsive bHLH factors modulate monoterpenoid indole
      alkaloid biosynthesis in Catharanthus roseus.
AB  - The pharmaceutically valuable monoterpene indole alkaloids (MIAs) in Catharanthus
      roseus are derived from the indole and iridoid pathways that respond to jasmonate
      (JA) signaling. Two classes of JA-responsive bHLH transcription factor (TF),
      CrMYC2 and BIS1/BIS2, are known to regulate the indole and iridoid pathways,
      respectively. However, upregulation of either one of the TF genes does not lead
      to increased MIA accumulation. Moreover, little is known about the
      interconnection between the CrMYC2 and BIS transcriptional cascades and the
      hierarchical position of BIS1/BIS2 in JA signaling. Here, we report that a newly
      identified bHLH factor, Repressor of MYC2 Targets 1 (RMT1), is activated by
      CrMYC2 and BIS1, and acts as a repressor of the CrMYC2 targets. In addition, we
      isolated and functionally characterized the core C. roseus JA signaling
      components, including CORONATINE INSENSITIVE 1 (COI1) and JASMONATE ZIM domain
      (JAZ) proteins. CrMYC2 and BIS1 are repressed by the JAZ proteins in the absence
      of JA, but de-repressed by the SCFCOI1 complex on perception of JA. Our findings
      suggest that the repressors, JAZs and RMT1, mediate crosstalk between the CrMYC2
      and BIS regulatory cascades to balance the metabolic flux in MIA biosynthesis.

PMID- 29178477
TI  - The anatomy of forearm free flap phalloplasty for transgender surgery.
AB  - Transgender surgeries are becoming more frequent and visual interpretation of
      anatomy is essential for both surgeons and patients. Since the forearm free flap
      phalloplasty was introduced in 1984, it has been known to provide reliable
      cosmetic and functional results for transitioning men compared with phalloplasty
      by different flaps. Surgical text descriptions were enhanced by the creation of
      new anatomic illustrations. The forearm free flap consists of the anterior
      forearm skin, subcutaneous tissue, fascia containing the radial artery as the
      perforator and its venae comitantes, cephalic and basilic veins, and lateral and
      medial antebrachial cutaneous nerves are demonstrated in relation to the
      surgically derived flap. Song's forearm free flap phalloplasty requires two
      surgical stages with a three-month interval between the stages: prelamination of
      a neourethra and construction of a neophallus. The neophallus created by forearm
      flap phalloplasty is reported to achieve acceptable aesthetical and psychological
      satisfaction, appropriate size and shape, and satisfying sexual intercourse.
      Despite increasing experiences in gender confirming surgery with modifications
      made by many authors, urethral complications including fistula and/or stricture
      formation are the leading causes of reoperation. The poor esthetic outcome of the
      forearm donor site and a decrease in rigidity of the neophallus are the main
      limitations. Illustrations of anatomy help inform surgical choice and
      understanding of risks and benefits by patients. The anatomy of the free forearm
      flap phalloplasty supports creation of a neophallus for transsexual anatomy
      revision. Clin. Anat. 31:145-151, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178478
TI  - From yeast to humans - roles of the Kennedy pathway for phosphatidylcholine
      synthesis.
AB  - The major phospholipid present in most eukaryotic membranes is
      phosphatidylcholine (PC), comprising ~ 50% of phospholipid content. PC metabolic
      pathways are highly conserved from yeast to humans. The main pathway for the
      synthesis of PC is the Kennedy (CDP-choline) pathway. In this pathway, choline is
      converted to phosphocholine by choline kinase, phosphocholine is metabolized to
      CDP-choline by the rate-determining enzyme for this pathway, CTP:phosphocholine
      cytidylyltransferase, and cholinephosphotransferase condenses CDP-choline with
      diacylglycerol to produce PC. This Review discusses how PC synthesis via the
      Kennedy pathway is regulated, its role in cellular and biological processes, as
      well as diseases known to be associated with defects in PC synthesis. Finally, we
      present the first model for the making of a membrane via PC synthesis.

PMID- 29178479
TI  - Face allotransplantation for various types of facial disfigurements: A series of
      five cases.
AB  - BACKGROUND: The aim of this report is to present our long-term experiences with a
      series of 5 face-transplanted patients in terms of surgical aspects and
      postoperative outcomes, and to describe possible salvage strategies in case of
      difficulties. METHODS: Five patients, 4 receiving full-face transplantation and 1
      undergoing partial transplantation at our institution were included. The patients
      were aged between 19 and 54 years. Two had extensive burn scars to the face, and
      3 had suffered gunshot injuries. The post-transplant induction immunosuppressive
      regimen included ATG combined with tacrolimus, mycophenolate mofetil, and
      prednisone, while maintenance was provided by the last 3. We focused on patient
      summaries including their etiologies, preoperative preparations, surgical
      techniques, immunosuppressive regimen, postoperative courses, revisional
      surgeries, together with challenges including acute rejection episodes, and
      immunosuppressive drug complications. RESULTS: No re-surgery due to vascular
      compromise was required in any case. One of the 5 patients was eventually lost
      due to complicated infectious and metabolic events at the end of post
      transplantation month 11. The other 4 patients were still alive, with a mean
      follow-up time of 53 months and had satisfactory functional transplants and
      cosmetic appearance. CONCLUSIONS: Face transplantation still involves challenges
      and many issues including compliance and psychological maturity of patients, the
      risk of opportunistic infections and malignancies still need to be resolved for
      it to be accepted as a safe procedure. Surgical rescue procedures considering
      ideal timing should be kept in mind strictly as one of the most important issues
      in case of unexpected events.

PMID- 29178481
TI  - Why do some birds carry their chicks?

PMID- 29178482
TI  - Hierarchical multi-taxa models inform riparian vs. hydrologic restoration of
      urban streams in a permeable landscape.
AB  - The degradation of streams caused by urbanization tends to follow predictable
      patterns; however, there is a growing appreciation for heterogeneity in stream
      response to urbanization due to the local geoclimatic context. Furthermore, there
      is building evidence that streams in mildly sloped, permeable landscapes respond
      uncharacteristically to urban stress calling for a more nuanced approach to
      restoration. We evaluated the relative influence of local-scale riparian
      characteristics and catchment-scale imperviousness on the macroinvertebrate
      assemblages of streams in the flat, permeable urban landscape of Perth, Western
      Australia. Using a hierarchical multi-taxa model, we predicted the outcomes of
      stylized stream restoration strategies to increase the riparian integrity at the
      local scale or decrease the influences of imperviousness at the catchment scale.
      In the urban streams of Perth, we show that local-scale riparian restoration can
      influence the structure of macroinvertebrate assemblages to a greater degree than
      managing the influences of catchment-scale imperviousness. We also observed an
      interaction between the effect of riparian integrity and imperviousness such that
      the effect of increased riparian integrity was enhanced at lower levels of
      catchment imperviousness. This study represents one of few conducted in flat,
      permeable landscapes and the first aimed at informing urban stream restoration in
      Perth, adding to the growing appreciation for heterogeneity of the Urban Stream
      Syndrome and its importance for urban stream restoration.

PMID- 29178480
TI  - Hydrogel Encapsulation Facilitates Rapid-Cooling Cryopreservation of Stem Cell
      Laden Core-Shell Microcapsules as Cell-Biomaterial Constructs.
AB  - Core-shell structured stem cell microencapsulation in hydrogel has wide
      applications in tissue engineering, regenerative medicine, and cell-based
      therapies because it offers an ideal immunoisolative microenvironment for cell
      delivery and 3D culture. Long-term storage of such microcapsules as cell
      biomaterial constructs by cryopreservation is an enabling technology for their
      wide distribution and ready availability for clinical transplantation. However,
      most of the existing studies focus on cryopreservation of single cells or cells
      in microcapsules without a core-shell structure (i.e., hydrogel beads). The goal
      of this study is to achieve cryopreservation of stem cells encapsulated in core
      shell microcapsules as cell-biomaterial constructs or biocomposites. To this end,
      a capillary microfluidics-based core-shell alginate hydrogel encapsulation
      technology is developed to produce porcine adipose-derived stem cell-laden
      microcapsules for vitreous cryopreservation with very low concentration (2 mol L
      1 ) of cell membrane penetrating cryoprotective agents (CPAs) by suppressing ice
      formation. This may provide a low-CPA and cost-effective approach for vitreous
      cryopreservation of "ready-to-use" stem cell-biomaterial constructs, facilitating
      their off-the-shelf availability and widespread applications.

PMID- 29178483
TI  - Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of
      intravenous bleomycin: analysis of 57 patients from the International Network for
      Sharing Practices of Electrochemotherapy registry.
AB  - BACKGROUND: Electrochemotherapy (ECT) is currently used to treat unresectable
      superficial tumours of different histotypes through the combination of cytotoxic
      chemotherapy and local application of electric pulses. In 2006, a collaborative
      project defined the ESOPE (European Standard Operating Procedures of
      Electrochemotherapy) guidelines to standardize the procedure. The International
      Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the
      ESOPE and improve clinical practice. Limiting patient exposure to systemic
      chemotherapy would be advisable to ameliorate ECT safety profile. OBJECTIVE: The
      aim of this study was to evaluate the efficacy and toxicity of ECT with reduced
      chemotherapy dosages. METHODS: In a retrospective analysis of a prospectively
      maintained database (InspECT registry), we evaluated the outcome of patients who
      received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m2 ,
      instead of the standard dose of 15 000 IU/m2 ). Tumour response in melanoma
      patients was compared with melanoma patients of the InspECT registry who received
      the standard dose of bleomycin. RESULTS: We identified 57 patients with 147
      tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma,
      17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per-tumour
      complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR
      was 57.9% (partial, 21.1%). Local pain was the most frequently reported side
      effect (n = 22 patients [39%]), mostly mild; two patients experienced flu-like
      symptoms, one patient nausea. We observed the same CR rate (55%) in patients with
      melanoma treated by reduced or conventional bleomycin dosages (P = 1.00).
      CONCLUSIONS: Electrochemotherapy performed with reduced bleomycin dosages could
      be as effective as with currently recommended dose. Patients with impaired renal
      function or candidate to multiple ECT cycles could benefit from a reduced dose
      protocol. Our findings need prospective confirmation before being adopted in
      clinical practice.

PMID- 29178484
TI  - A Single Mutation is Sufficient to Modify the Metal Selectivity and Specificity
      of a Eukaryotic Manganese Superoxide Dismutase to Encompass Iron.
AB  - We have generated a site-directed mutant of the manganese superoxide dismutase
      SOD-3 of C.elegans (MnSOD-3) which modifies the metal specificity of the enzyme.
      While wild-type MnSOD-3 functions with manganese in the active site (3600 U mg-1
      of protein) it has little or no activity when iron is incorporated. However, when
      histidine replaces glutamine 142 in the active site, the enzyme retains 50 % of
      its activity and becomes cambialistic for its metal cofactor exhibiting very
      similar specific activity with either manganese or iron.

PMID- 29178485
TI  - Shelf-Life of Boiled Salted Duck Meat Stored Under Normal and Modified
      Atmosphere.
AB  - : The objective of this study was to investigate the physicochemical properties
      and changes in the microbial counts of boiled salted duck (BSD) meat packed under
      various conditions. BSD meat was stored under normal atmosphere (C) and two
      modified atmosphere packaging (MAP) conditions: M1 (N2 , 100%) and M2 (CO2 /N2 ,
      30%/70%) at 4  degrees C. Microbiological quality, pH, redness, lipid oxidation,
      headspace gas composition, and water activity of BSD meat were measured. The
      results showed that the time to reach the maximum acceptable total viable counts
      (TVC, 4.9 log CFU/g) was 12, 18, and 21 d in C, M1, and M2 samples, respectively.
      Significant difference in the redness values was observed in all treatments
      during storage. The redness value of C group was significantly lower than that in
      M1 and M2 groups at the end of storage. The thiobarbituric acid-reactive
      substances (TBARS) values under MAP were 0.24 to 0.26 mg MDA/kg meat at the end
      of storage, lower (P < 0.05) than that in C group (0.78 mg MDA/kg meat). The
      water activity in M2 group was the lowest among all 3 groups. The CO2
      concentration in M2 decreased significantly during storage. Our study
      demonstrates that packaging with 30% CO2 and 70% N2 (M2) could extend the shelf
      life of BSD meat to 21 d during storage at 4  degrees C, suggesting that MAP can
      be a practical approach to extend the shelf-life and maintain the quality of BSD
      products. PRACTICAL APPLICATION: This study evaluated the application of MAP for
      a cooked duck product. Our results showed that MAP can be utilized to extend the
      shelf-life. This technology may be used for preservation of other cooked meat
      products.

PMID- 29178486
TI  - Developing and characterizing MR/CT-visible materials used in QA phantoms for
      MRgRT systems.
AB  - PURPOSE: Synthetic tissue equivalent (STE) materials currently used to simulate
      tumor and surrounding tissues for IROC-Houston's anthropomorphic head and thorax
      QA phantoms cannot be visualized using magnetic resonance (MR) imaging. The
      purpose of this study was to characterize dual MR/CT-visible STE materials that
      can be used in an end-to-end QA phantom for MR-guided radiotherapy (MRgRT)
      modalities. METHODS: Over 80 materials' MR, CT, and dosimetric STE properties
      were investigated for use in MRgRT QA phantoms. The materials tested included
      homogeneous and heterogeneous materials to simulate soft tissue/tumor and lung
      tissues. Materials were scanned on a Siemens' Magnetom Espree 1.5 T using four
      sequences, which showed the materials visual contrast between T1- and T2-weighted
      images. Each material's Hounsfield number and electron density data was collected
      using a GE's CT Lightspeed Simulator. Dosimetric properties were examined by
      constructing a 10 * 10 * 20 cm3 phantom of the selected STE materials that was
      divided into three sections: anterior, middle, and posterior. Anterior and
      posterior pieces were composed of polystyrene, whereas the middle section was
      substituted with the selected STE materials. EBT3 film was inserted into the
      phantom's midline and was irradiated using an Elekta's Versa 6 MV beam with a
      prescription of 6 Gy at 1.5 cm and varying field size of: 10 * 10 cm2 , 6 * 6 cm2
      , and 3 * 3 cm2 . Measured film PDD curves were compared to planning system
      calculations and conventional STE materials' percent depth dose (PDD) curves.
      RESULTS: The majority of the tested materials showed comparable CT attenuation
      properties to their respective organ site; however, most of the tested materials
      were not visible on either T1- or T2-weighted MR images. Silicone, hydrocarbon,
      synthetic gelatin, and liquid PVC plastic-based materials showed good MR image
      contrast. In-house lung equivalent materials made with either silicone- or
      hydrocarbon-based materials had HUs ranging from: -978 to -117 and -667 to -593,
      respectively. Synthetic gelatin and PVC plastic-based materials resembled soft
      tissue/tumor equivalent materials and had HUs of: -175 to -170 and -29 to 32,
      respectively. PDD curves of the selected MR/CT-visible materials were comparable
      to IROC-Houston's conventional phantom STE materials. The smallest field size
      showed the largest disagreements, where the average discrepancies between
      calculated and measured PDD curves were 1.8% and 5.9% for homogeneous and
      heterogeneous testing materials, respectively. CONCLUSIONS: Gelatin, liquid
      plastic, and hydrocarbon-based materials were determined as alternative STE
      substitutes for MRgRT QA phantoms.

PMID- 29178487
TI  - Therapeutic Benefit of Smoked Cannabis in Randomized Placebo-Controlled Studies.
AB  - The medicinal use of marijuana has been legalized in 28 states, with a wide range
      of specificity for approved medical conditions. Even with the emergence of non
      combustion-based delivery systems, 90% of marijuana users in 2014 used smoked
      marijuana. This review summarizes the data available on the use of smoked
      marijuana for medical purposes. A literature search was performed to retrieve
      randomized controlled trials exploring the efficacy of smoked cannabis for
      treatment of a medical condition. Studies with the primary end point listed as
      the effect of smoked cannabis on a disease-specific characteristic were included.
      Open-label studies and studies using other administration methods were excluded.
      Seven studies met these criteria and were included in this review. Cannabis did
      not outperform placebo on experimentally evoked pain or the timed walk test.
      Clear evidence indicates that smoked cannabis reduces intraocular pressure, but
      the effect is too brief (less than 4 hrs) to be of therapeutic benefit for this
      chronic disorder. Consistent evidence also showed that smoked marijuana, even at
      lower concentrations of tetrahydrocannabinol, increased total daily calorie
      intake and number of eating occasions. Neither of the studies with quality of
      life as secondary outcome measures revealed statistically significantly improved
      outcomes with cannabis use.

PMID- 29178488
TI  - The anatomy of abdominal flap phalloplasty for transgender surgery.
AB  - Abdominal flap phalloplasty is surgical construction of a neophallus using a
      pedicled abdominal flap for patients transitioning female to male, for males
      whose penis is congenitally absent, or lost from trauma. It is an option for
      trans men whose goals do not require urethroplasty or vaginectomy but would like
      a phallus suitable for male gender appearance. A prosthesis can be placed for
      penetrative sexual capability. Surgical text descriptions were enhanced by
      creation of new anatomic illustrations. Anatomy of donor site and surgical
      technique leading to creation of the neophallus are demonstrated in detail with
      new relevant illustrations. Significant structures of the donor site of the
      abdominal flap include the superficial external pudendal artery and ilioinguinal
      nerve that provide the blood supply and sensory innervation to the base of the
      flap, respectively. As a pedicled phalloplasty procedure, microsurgical
      anastomosis is not needed. Patients can expect to have tactile sensation but not
      innate rigidity. The dorsal nerve of clitoris (and sometimes the clitoris itself)
      is preserved to provide erogenous sensation. Abdominal flap phalloplasty makes it
      possible to maintain the natural blood supply and innervation to the neophallus.
      The neophallus created by abdominal flap phalloplasty has the advantage of
      homogeneous skin color and texture from contiguous skin. Grafting leaves a less
      stigmatizing horizontal scar running from one side of the pelvis to the other
      along the lower abdomen. The anatomy of the abdominal flap phalloplasty supports
      creation of a neophallus for transsexual anatomy revision. Clin. Anat. 31:181
      186, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178489
TI  - Daily inspiratory muscle training lowers blood pressure and vascular resistance
      in healthy men and women.
AB  - NEW FINDINGS: What is the central question of this study? What impact does
      inspiratory muscle training have on systemic vascular resistance, cardiac output
      and baroreflex sensitivity in adult men and women? What is the main finding and
      its importance? Inspiratory muscle training exerts favorable effects on blood
      pressure, vascular resistance and perception of stress. This exercise format is
      well-tolerated and equally effective whether implemented in men or women.
      ABSTRACT: Previous work has shown that inspiratory muscle training (IMT) lowers
      blood pressure after a mere 6 weeks, identifying IMT as a potential therapeutic
      intervention to prevent or treat hypertension. Here, we explore the effects of
      IMT on respiratory muscle strength and select cardiovascular parameters in
      recreationally active men and women. Subjects were randomly assigned to IMT (n =
      12, 75% maximal inspiratory pressure) or sham training (n = 13, 15% maximal
      inspiratory pressure) groups and underwent a 6-week intervention comprising 30
      breaths day-1 , 5 days week-1 . Pre- and post-training measures included maximal
      inspiratory pressure and resting measures of blood pressure, cardiac output,
      heart rate, spontaneous cardiac baroreflex sensitivity and systemic vascular
      resistance. We evaluated psychological and sleep status via administration of the
      Cohen-Hoberman inventory of physical symptoms and the Epworth sleepiness scale.
      Male and female subjects in the IMT group showed declines in systolic/diastolic
      blood pressures (-4.3/-3.9 mmHg, P < 0.025) and systemic vascular resistance (
      3.5 mmHg min l-1 , P = 0.008) at week 6. There was no effect of IMT on cardiac
      output (P = 0.722), heart rate (P = 0.795) or spontaneous cardiac baroreflex
      sensitivity (P = 0.776). The IMT subjects also reported fewer stress-related
      symptoms (pre- versus post-training, 12.5 +/- 8.5 versus 7.2 +/- 9.7, P = 0.025).
      Based on these results, we suggest that a short course of IMT confers significant
      respiratory and cardiovascular improvements and parallel (modest) psychological
      benefits in healthy men and women.

PMID- 29178490
TI  - A Bifunctional Perovskite Promoter for Polysulfide Regulation toward Stable
      Lithium-Sulfur Batteries.
AB  - Lithium-sulfur (Li?S) batteries are strongly considered as the next-generation
      rechargeable cells. However, both the shuttle of lithium polysulfides (LiPSs) and
      sluggish kinetics in random deposition of lithium sulfides (Li2 S) significantly
      degrade the capacity, rate performance, and cycling life of Li?S cells. Herein,
      bifunctional Ba0.5 Sr0.5 Co0.8 Fe0.2 O3-delta perovskite nanoparticles (PrNPs)
      are proposed as a promoter to immobilize LiPSs and guide the deposition of Li2 S
      in a Li?S cell. The oxygen vacancy in PrNPs increases the metal reactivity to
      anchor LiPSs, and co-existence of lithiophilic (O) and sulfiphilic (Sr) sites in
      PrNP favor the dual-bonding (Li?O and Sr?S bonds) to anchor LiPSs. The high
      catalytic nature of PrNP facilitates the kinetics of LiPS redox reaction. The
      PrNP with intrinsic LiPS affinity serves as nucleation sites for Li2 S deposition
      and guides its uniform propagation. Therefore, the bifunctional LiPS promoter in
      Li?S cell yields high rate performance and ultralow capacity decay rate of 0.062%
      (a quarter of pristine Li?S cells). The proposed strategy to immobilize LiPSs,
      promotes the conversion of LiPS, and regulates deposition of Li2 S by an emerging
      perovskite promoter and is also expected to be applied in other energy conversion
      and storage devices based on multi-electron redox reactions.

PMID- 29178491
TI  - Pharmacokinetic and Pharmacodynamic Modeling of Serum Etrolizumab and Circulating
      beta7 Receptor Occupancy in Patients With Ulcerative Colitis.
AB  - Etrolizumab, a humanized monoclonal antibody, specifically binds to the beta7
      subunit of the heterodimeric integrins alpha4beta7 and alphaEbeta7.
      Pharmacokinetic (PK) and pharmacodynamic (PD) data were collected from an
      etrolizumab phase 1 trial in patients with moderate to severe ulcerative colitis
      (UC). We developed a mechanism-based model to simultaneously describe the
      kinetics of serum etrolizumab concentration and free beta7 receptors on
      circulating intestinal-homing CD4+ T lymphocytes. Included in the analysis were
      38 phase 1 UC patients who received single or 3 monthly doses of etrolizumab
      intravenously or subcutaneously across a dose range of 0.3 to 10 mg/kg. A quasi
      steady-state target-mediated drug disposition model was developed to describe the
      dynamic interaction between serum etrolizumab concentration and free beta7
      receptors on intestinal-homing CD4+ T lymphocytes in UC patients. The time
      profiles of serum etrolizumab and absolute counts of beta7+ lymphocytes
      (expressed as percentage of baseline level) were well described by the quasi
      steady-state target-mediated drug disposition model. The model was able to
      characterize the maximum drug occupancy of beta7 receptors on intestinal-homing
      CD4+ T lymphocytes and the concentration-dependent duration of occupancy. The 90%
      effective concentration for etrolizumab to saturate the beta7 receptors on
      intestinal homing CD4+ T cells was 1.3 MUg/mL. PK and PD profiles predicted by
      the model were consistent with observations from a subsequent phase 2 study. In
      conclusion, an integrated PK/PD model developed in this analysis reasonably
      described serum etrolizumab PK profiles and the relationship between PK and PD
      (free beta7 receptors on circulating intestinal-homing CD4+ T lymphocytes) in UC
      patients.

PMID- 29178492
TI  - Contactless Visualization of Latent Fingerprints on Nonporous Curved Surfaces of
      Circular Cross Section-A Statistical Evaluation on the Materials as Plane Mirror.
AB  - A new contactless technique for latent fingerprint visualization on nonporous
      curved surfaces of circular cross section was introduced by Low et al. (1). The
      technique utilizes a plane mirror to convey the light rays toward the inspected
      surfaces for latent fingerprint visualization. This research activity came up as
      an extension of the previous study which utilized an aluminum plate as the plane
      mirror to illuminate the inspected surfaces. Dulling spray was used to increase
      the diffuse component of the reflective aluminum plate. However, the amount of
      dulling spray will affect the uniformity of the illumination on the inspected
      curved surfaces. In this study, a study on the new materials for the plane mirror
      was carried out. Coated aluminum, opal, and ground glass diffusers were selected
      as the new materials. The performance of the new materials was compared to the
      aluminum based on the quality of the captured images on various nonporous
      cylindrical surfaces. A statistical approach known as randomized complete block
      design was used to design the experiment. The quality of the captured images was
      obtained using Spectral Image Validation and Verification. Two-way analysis of
      variance and Fisher's least significant difference test were used to analyze the
      quality of the images. From the results of the statistical analysis, coated
      aluminum has the best performance compared to aluminum, opal, and ground glass
      diffusers.

PMID- 29178493
TI  - Can MM/GBSA calculations be sped up by system truncation?
AB  - We have studied whether calculations of the binding free energy of small ligands
      to a protein by the MM/GBSA approach (molecular mechanics combined with
      generalized Born and surface area solvation) can be sped up by including only a
      restricted number of atoms close to the ligand. If the protein is truncated
      before the molecular dynamics (MD) simulations, quite large changes are observed
      for the calculated binding energies, for example, 4 kJ/mol average difference for
      a radius of 19 A for the binding of nine phenol derivatives to ferritin. The
      results are improved if no atoms are fixed in the simulations, with average and
      maximum errors of 2 and 3 kJ/mol at 19 A and 3 and 6 kJ/mol at 7 A. Similar
      results are obtained for two additional proteins, p38alpha MAP kinase and factor
      Xa. On the other hand, if energies are calculated on snapshots that are truncated
      after the MD simulation, all residues more than 8.5 A from the ligand can be
      omitted without changing the energies by more than 1 kJ/mol on average (maximum
      error 1.4 kJ/mol). At the molecular mechanics level, the gain in computer time
      for such an approach is small. However, it shows what size of system should be
      used if the energies instead are calculated with a more demanding method, for
      example, quantum-mechanics. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178494
TI  - Microvascular characteristics of the acoustic fats: Novel data suggesting
      taxonomic differences between deep and shallow-diving odontocetes.
AB  - Odontocetes have specialized mandibular fats, the extramandibular (EMFB) and
      intramandibular fat bodies (IMFB), which function as acoustic organs, receiving
      and channeling sound to the ear during hearing and echolocation. Recent
      strandings of beaked whales suggest that these fat bodies are susceptible to
      nitrogen (N2 ) gas embolism and empirical evidence has shown that the N2
      solubility of these fat bodies is higher than that of blubber. Since N2 gas will
      diffuse from blood into tissue at any blood/tissue interface and potentially form
      gas bubbles upon decompression, it is imperative to understand the extent of
      microvascularity in these specialized acoustic fats so that risk of embolism
      formation when diving can be estimated. Microvascular density was determined in
      the EMFB, IMFB, and blubber from 11 species representing three odontocete
      families. In all cases, the acoustic tissues had less (typically 1/3 to 1/2)
      microvasculature than did blubber, suggesting that capillary density in the
      acoustic tissues may be more constrained than in the blubber. However, even
      within these constraints there were clear phylogenetic differences. Ziphiid
      (Mesoplodon and Ziphius, 0.9 +/- 0.4% and 0.7 +/- 0.3% for EMFB and IMFB,
      respectively) and Kogiid families (1.2 +/- 0.2% and 1.0 +/- 0.01% for EMFB and
      IMFB, respectively) had significantly lower mean microvascular densities in the
      acoustic fats compared to the Delphinid species (Tursiops, Grampus, Stenella, and
      Globicephala, 1.3 +/- 0.3% and 1.3 +/- 0.3% for EMFB and IMFB, respectively).
      Overall, deep-diving beaked whales had less microvascularity in both mandibular
      fats and blubber compared to the shallow-diving Delphinids, which might suggest
      that there are differences in the N2 dynamics associated with diving regime,
      phylogeny, and tissue type. These novel data should be incorporated into diving
      physiology models to further understand potential functional disruption of the
      acoustic tissues due to changes in normal diving behavior.

PMID- 29178495
TI  - Novel device-based acne treatments: comparison of a 1450-nm diode laser and
      microneedling radiofrequency on mild-to-moderate acne vulgaris and seborrhoea in
      Korean patients through a 20-week prospective, randomized, split-face study.
AB  - BACKGROUND: While device-based acne treatments are widely applied for patients
      not tolerating conventional medications, related controlled studies have been
      still limited. Recently, non-ablative 1450-nm diode laser (DL) and fractional
      microneedling radiofrequency (FMR) have been effectively used for acne, in
      addition to well-recognized dermal remodelling effects. OBJECTIVE: To compare the
      clinical course of acne treatment between DL and FMR. METHODS: Twenty-five Korean
      patients with mild-to-moderate facial acne completed treatments with DL and FMR
      through a 20-week, randomized split-face study. One randomly assigned half side
      of each patient's face received DL and the other side by FMR. Treatments were
      scheduled to receive three consecutive sessions at 4-week intervals. Objective
      assessments including revised Leeds grades, lesion counts, sebum output
      measurements, and patients' subjective satisfaction were investigated. RESULTS:
      Both DL and FMR demonstrated steady improvement of acne and seborrhoea during
      treatment sessions. While results between two devices were similar during
      treatment sessions, FMR was superior to DL in the 12-week follow-up. Patients'
      subjective assessments for seborrhoea improvement were similar between two
      devices, while those for acne, skin texture, and acne scars were more
      satisfactory for FMR. For safety profile, no significant difference was observed
      between two regimens, while mild postinflammatory hyperpigmentation was observed
      only in DL side. CONCLUSION: Both DL and FMR demonstrated efficacies for acne and
      seborrhoea, with reasonable safety profile. FMR was more effective than DL for
      the long-term maintenance, and subjective assessments for texture and scar
      improvements. Therefore, a few sessions of these devices would be a viable option
      for acne treatments.

PMID- 29178496
TI  - Kisspeptin, gonadotrophin-releasing hormone and oestrogen receptor alpha
      colocalise with neuronal nitric oxide synthase neurones in prepubertal female
      sheep.
AB  - Puberty is a process that integrates multiple inputs ultimately resulting in an
      increase in gonadotrophin-releasing hormone (GnRH) secretion. Although kisspeptin
      neurones play an integral role in GnRH secretion and puberty onset, other systems
      are also likely important. One potential component is nitric oxide (NO), a
      gaseous neurotransmitter synthesised by nitric oxide synthase (NOS). The present
      study aimed to neuroanatomically characterise neuronal NOS (nNOS) in prepubertal
      female sheep and determine whether oestradiol exerts effects on this system.
      Luteinising hormone secretion was reduced by oestradiol treatment in prepubertal
      ovariectomised ewes. Neurones immunoreactive for nNOS were identified in several
      areas, with the greatest number present in the ventrolateral portion of the
      ventromedial hypothalamus, followed by the ventromedial hypothalamus, preoptic
      area (POA) and arcuate nucleus (ARC). Next, we determined whether nNOS neurones
      contained oestrogen receptor (ER)alpha and could potentially communicate
      oestradiol (E2 ) feedback to GnRH neurones. Neuronal NOS neurones contained
      ERalpha with the percentage of coexpression (12%-40%) depending upon the area
      analysed. We next investigated whether a neuroanatomical relationship existed
      between nNOS and kisspeptin or nNOS and GnRH neurones. A high percentage of
      kisspeptin neurones in the POA (79%) and ARC (98%) colocalised with nNOS.
      Kisspeptin close contacts were also associated with nNOS neurones. A greater
      number of close contacts were observed in the ARC than the POA. A high percentage
      of POA GnRH neurones (79%) also expressed nNOS, although no GnRH close contacts
      were observed onto nNOS neurones. Neither the numbers of nNOS neurones in the POA
      or hypothalamus, nor the percentage of nNOS coexpression with GnRH, kisspeptin or
      ERalpha were influenced by oestradiol. These experiments reveal that a
      neuroanatomical relationship exists between both nNOS and kisspeptin and nNOS and
      GnRH in prepubertal ewes. Therefore, nNOS may act both directly and indirectly to
      influence GnRH secretion in prepubertal sheep.

PMID- 29178497
TI  - How to perform posterior wall isolation in catheter ablation for atrial
      fibrillation.
AB  - Catheter ablation has become standard of care in patients with symptomatic atrial
      fibrillation (AF). Although there have been significant advances in our
      understanding and technology, a substantial proportion of patients have ongoing
      AF requiring repeat procedures. Pulmonary vein isolation (PVI) is the cornerstone
      of AF ablation; however, it is less effective in patients with persistent as
      opposed to paroxysmal atrial fibrillation. Left atrial posterior wall isolation
      (PWI) is commonly performed as an adjunct to PVI in patients with persistent AF
      with nonrandomized studies showing improved outcomes. Anatomical considerations
      and detailed outline of the various approaches and techniques to performing PWI
      are detailed, and advantages and pitfalls to assist the clinical
      electrophysiologist successfully and safely complete PWI are described.

PMID- 29178498
TI  - Technical Note: Solving the "Chinese postman problem" for effective contour
      deformation.
AB  - PURPOSE: To develop a practical approach for accurate contour deformation when
      deformable image registration (DIR) is used for atlas-based segmentation or
      contour propagation in image-guided radiotherapy. METHODS: We developed a contour
      deformation approach based on 3D mesh operations. The 2D contours represented by
      a series of points in each slice were first converted to a 3D triangular mesh,
      which was deformed by the deformation vectors resulting from DIR. A set of
      parallel 2D planes then cut through the deformed 3D mesh, generating unordered
      points and line segments, to be reorganized into a set of 2D contour points. The
      reorganization problem was equivalent to solving the "Chinese postman problem"
      (CPP) by traversing a graph built from the unordered points with the least cost.
      Alternatively, deformation could be applied to a binary image converted from the
      original contours. The deformed binary image was then converted back into
      contours at the CT slice locations. We validated the mesh-based contour
      deformation approach using lung and heart contours from 10 patients with thoracic
      cancer. RESULTS: DIR could change the 3D mesh considerably, complicating 2D
      contour representations after deformation. CPP could effectively reorganize the
      points in 2D planes regardless of how complicated the 2D contours were. Among the
      10 patients, the Dice similarity coefficient between the mesh-based contour and
      binary image-based contour was 97.6% +/- 0.3% for lung and 97.5% +/- 0.7% for
      heart, and the Hausdoroff distance between them was 19.8 +/- 5.1 mm for lung and
      6.1 +/- 2.2 mm for heart. Subjective evaluation showed that the mesh-based
      approach could keep fine details, especially for the lung. The image-based
      approach seemed to overprocess contours and suffered from image resolution
      limits. CONCLUSION: We developed a practical approach for accurate contour
      deformation and demonstrated its effectiveness for both clinical and research
      applications.

PMID- 29178499
TI  - AANEM policy statement on electrodiagnosis for distal symmetric polyneuropathy.
AB  - Electrodiagnostic (EDX) studies are often very helpful in the diagnosis and
      management of patients who have or are suspected to have Distal Symmetric
      Polyneuropathy (DSP). However, EDX studies may not be appropriate in every
      situation. There are five common scenarios in which EDX studies are likely to be
      beneficial: (1) determining primary and alternative diagnoses; (2) determining
      severity, duration and prognosis of disease; (3) evaluating risk of associated
      problems; (4) determining the effect of medications; and (5) evaluating the
      effect of toxic exposures. Muscle Nerve 57: 337-339, 2018.

PMID- 29178500
TI  - Identifying unique subtypes of spinal afferent nerve endings within the urinary
      bladder of mice.
AB  - Spinal afferent neurons are responsible for the transduction and transmission of
      noxious (painful) stimuli and innocuous stimuli that do not reach conscious
      sensations from visceral organs to the central nervous system. Although the
      location of the nerve cell bodies of spinal afferents is well known to reside in
      dorsal root ganglia (DRG), the morphology and location of peripheral nerve
      endings of spinal afferents that transduce sensory stimuli into action potentials
      is poorly understood. The individual nerve endings of spinal afferents that
      innervate the urinary bladder have never been unequivocally identified in any
      species. We used an anterograde tracing technique developed in our laboratory to
      selectively label only spinal afferents. Mice were anesthetized and unilateral
      injections of dextran-amine made into lumbosacral DRGs (L5-S2). Seven to nine
      days postsurgery, mice were euthanized, the urinary bladder removed, then fresh
      fixed and stained for immunoreactivity to calcitonin-gene-related-peptide (CGRP).
      Four distinct morphological types of spinal afferent ending in the bladder were
      identified. Three types existed in the detrusor muscle and one major type in the
      sub-urothelium and urothelium. Most nerve endings were located in detrusor muscle
      where the three types could be identified as having: "branching", "simple", or
      "complex" morphology. The majority of spinal afferent nerve endings were CGRP
      immunoreactive. Single spinal afferent axons bifurcated many times upon entering
      the bladder and developed varicosities along their axon terminal endings. We
      present the first morphological identification of spinal afferent nerve endings
      in the mammalian urinary bladder.

PMID- 29178501
TI  - In vivo reflectance confocal microscopy image interpretation for the
      dermatopathologist.
AB  - Reflectance confocal microscopy (RCM) is a technology utilized for bedside
      diagnosis of cutaneous pathology by non-invasive, in vivo, cellular-level
      imaging. With the recent establishment of reimbursement codes by the US Centers
      for Medicaid and Medicare Services, RCM is now likely to be employed by clinical
      dermatologists and impact decision making on skin cancer management.
      Dermatopathologists, therefore, would benefit from learning how to interpret RCM
      images and how RCM findings correlate with histopathological criteria of
      diagnosis. This review briefly explains the principles behind RCM image
      acquisition, describes the key RCM features of normal skin, and delineates the
      RCM characteristics of frequently observed benign and malignant neoplasms.

PMID- 29178502
TI  - Survival times with and without tube feeding in patients with dementia or
      psychiatric diseases in Japan.
AB  - BACKGROUND: It is widely supposed that there has been no evidence of increased
      survival in patients with advanced dementia receiving enteral tube feeding.
      However, more than a few studies have reported no harmful outcome from tube
      feeding in dementia patients compared to in patients without dementia. METHODS:
      This was a retrospective study. Nine psychiatric hospitals in Okayama Prefecture
      participated in this survey. All inpatients fulfilling the entry criteria were
      evaluated. All subjects suffered from difficulty with oral intake. Attending
      physicians thought that the patients could not live without long-term artificial
      nutrition. The physicians decided whether to make use of long-term artificial
      nutrition between January 2012 and December 2014. RESULTS: We evaluated 185
      patients. Their mean age was 76.6 +/- 11.4 years. Of all subjects, patients with
      probable Alzheimer's disease (n = 78) formed the biggest group, schizophrenia
      patients (n = 44) the second, and those with vascular dementia (n = 30) the
      third. The median survival times were 711 days for patients with tube feeding and
      61 days for patients without tube feeding. In a comparison different types of
      tube feeding, median survival times were 611 days for patients with a nasogastric
      tube and more than 1000 days for those with a percutaneous endoscopic gastrostomy
      tube. CONCLUSION: Patients with tube feeding survived longer than those without
      tube feeding, even among dementia patients. This study suggests that enteral
      nutrition for patients with dementia prolongs survival. Additionally,
      percutaneous endoscopic gastrostomy tube feeding may be safer than nasogastric
      tube feeding among patients in psychiatric hospitals.

PMID- 29178504
TI  - Spontaneous left atrial echo contrast, mitral annular systolic velocity, and left
      atrial appendage late emptying velocity in predicting improvement of left atrial
      function after percutaneous balloon mitral valvuloplasty.
AB  - BACKGROUND: Thromboembolic events are the major cause of morbidity and mortality
      in patients with mitral stenosis (MS). This study aims to investigate left atrial
      spontaneous echo contrast (LA SEC), mitral annular systolic velocity (Sa-wave),
      left atrial appendage (LAA) late emptying velocity (LAAEV), LAA filling velocity
      (LAAFV) pre- and postpercutaneous balloon mitral valvuloplasty (PBMV) for MS.
      This also aims to study the association of LA SEC with inflammatory marker, high
      sensitivity C-reactive protein (hs-CRP) in MS. METHODS: The study population
      consisted of 100 patients with symptomatic MS with sinus rhythm who underwent
      PBMV. Transthoracic echo (TTE), tissue Doppler imaging (TDI), and transesophageal
      echo (TEE) examinations were carried out before and 14 days following PBMV. High
      sensitivity C-reactive protein (hs-CRP) was measured at the time of admission.
      RESULTS: The mean age was 33.2 +/- 10.3 years with female preponderance (71%).
      There was a decrease in SEC grading, (pre-PBMV 2.8 +/- 0.9 and post-PBMV 0.4 +/-
      0.1; P < .01), increase in LAAEV (pre-PBMV 23.0 +/- 7.9 cm/s and post-PBMV 40.9
      +/- 8.4 cm/s; P < .01), and LAAFV (pre-PBMV 31.8 +/- 9.3 cm/s and post-PBMV 51.2
      +/- 8.7 cm/s; P < .01).A significant positive correlation was present between
      LAAEV and Sa-wave (r = .52, P < .01). Correlation between hs-CRP and SEC was
      positive and significant (r = .33, P < .01). Optimal cutoff value of hs-CRP for
      prediction of moderate to dense SEC was >2.3 mg/dL, the cutoff value of Sa-wave
      was<= 5.5 cm/s for prediction of the presence of inactive LAA (LAAEV < 25 cm/s).
      CONCLUSION: Mitral annular systolic velocity (Sa-wave) is an independent
      predictor of inactive LAA and a useful parameter in estimating inactive LAA in
      MS. Sa-wave and hs-CRP are independent predictors for SEC. PBMV improves LAA
      function in patients with MS.

PMID- 29178505
TI  - Expression levels of taste-related genes in palate and tongue tip, and
      involvement of transient receptor potential subfamily M member 5 (TRPM5) in taste
      sense in chickens.
AB  - The elucidation of the mechanisms underlying the taste sense of chickens will
      contribute to improvements in poultry feeding, because the molecular mechanism of
      chickens' taste sense defines the feeding behavior of chickens. Here we focused
      on the gene expressions in two different oral tissues of chickens - the palate,
      which contains many taste buds, and the tongue tip, which contains few taste
      buds. Using the quantitative real-time polymerase chain reaction method, we found
      that the molecular markers for taste buds of chickens, that is alpha-gustducin
      and vimentin, were expressed significantly highly in the palate compared to the
      tongue tip. Our analyses also revealed that transient receptor potential
      subfamily M member 5 (TRPM5), a cation channel involved in taste transduction in
      mammals, was also highly expressed in the palate compared to the tongue tip. Our
      findings demonstrated that the expression patterns of these genes were
      significantly correlated. We showed that the aversion to bitter solution was
      alleviated by a TRPM5 inhibitor in behavior of chickens. Taken together, our
      findings enabled us to develop a simple method for screening taste-related genes
      in chickens. The use of this method demonstrated that TRPM5 was involved in
      chickens' taste transduction, and that a TRPM5 inhibitor can alleviate chickens'
      bitter taste perception of feed ingredients.

PMID- 29178506
TI  - Complications and short-term outcomes associated with single-port laparoscopic
      splenectomy in dogs.
AB  - OBJECTIVE: To describe a technique and report complications and outcome for
      single-port laparoscopic splenectomy in dogs. STUDY DESIGN: Retrospective study.
      ANIMALS: Twenty-two client-owned dogs. METHODS: Medical records of dogs that
      underwent single-port laparoscopic splenectomy at 4 veterinary teaching hospitals
      were evaluated. Commercially available single-port devices were used in all dogs.
      In all cases, a vessel-sealing device was used to perform a hilar splenectomy.
      After the procedure was completed, the spleen was exteriorized through the single
      port device incision or placed into a specimen retrieval device; enlargement of
      the incision was required in some cases. RESULTS: Median weight of dogs was 9.9
      kg (interquartile range [IQR], 7.0-26.0). Splenectomy was performed because of
      splenic mass (n = 14), diffuse splenic disease (n = 4), or as adjunctive
      treatment for management of immune-mediated disease (n = 4). In cases with
      splenic masses, median maximal diameter of the largest splenic mass was 2.0 cm
      (IQR, 1.3-2.5). In 6 of 22 cases, mild splenic capsular bleeding occurred during
      the procedure. Conversion occurred in 6 of 22 cases to either a laparoscopic
      assisted approach (n = 5) or an open celiotomy (n = 1). Reasons for conversion
      included large splenic dimensions (n = 3), adhesion formation (n = 1) or poor
      visualization resulting from abundant intra-abdominal fat (n = 1) or hemorrhage
      (n = 1). Heavier body weight was significantly associated with conversion (odds
      ratio, 1.62; 95% confidence interval, 1.05-2.51), but body condition score,
      having a splenic mass, splenic mass size, and surgical time were not. CONCLUSION:
      Single-port laparoscopic splenectomy is an effective approach for elective
      splenectomy in dogs. The technique may be well suited to smaller dogs with
      modestly sized splenic masses or diffuse splenic disease.

PMID- 29178507
TI  - Is Doppler ultrasonography of value for the differentiation between noninvasive
      follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and
      invasive encapsulated follicular variant of papillary thyroid carcinoma?

PMID- 29178508
TI  - Predictive accuracy of combined genetic and environmental risk scores.
AB  - The substantial heritability of most complex diseases suggests that genetic data
      could provide useful risk prediction. To date the performance of genetic risk
      scores has fallen short of the potential implied by heritability, but this can be
      explained by insufficient sample sizes for estimating highly polygenic models.
      When risk predictors already exist based on environment or lifestyle, two key
      questions are to what extent can they be improved by adding genetic information,
      and what is the ultimate potential of combined genetic and environmental risk
      scores? Here, we extend previous work on the predictive accuracy of polygenic
      scores to allow for an environmental score that may be correlated with the
      polygenic score, for example when the environmental factors mediate the genetic
      risk. We derive common measures of predictive accuracy and improvement as
      functions of the training sample size, chip heritabilities of disease and
      environmental score, and genetic correlation between disease and environmental
      risk factors. We consider simple addition of the two scores and a weighted sum
      that accounts for their correlation. Using examples from studies of
      cardiovascular disease and breast cancer, we show that improvements in
      discrimination are generally small but reasonable degrees of reclassification
      could be obtained with current sample sizes. Correlation between genetic and
      environmental scores has only minor effects on numerical results in realistic
      scenarios. In the longer term, as the accuracy of polygenic scores improves they
      will come to dominate the predictive accuracy compared to environmental scores.

PMID- 29178509
TI  - Oral immunization with a Lactobacillus casei-based anti-porcine epidemic
      diarrhoea virus (PEDV) vaccine expressing microfold cell-targeting peptide Co1
      fused with the COE antigen of PEDV.
AB  - AIMS: The aims of this study were to develop an effective M cell-targeting oral
      vaccine, involving Lactobacillus casei to deliver the porcine epidemic diarrhoea
      virus (PEDV) core neutralizing epitope (COE) antigen conjugated with M cell
      targeting peptide Co1 as an adjuvant, against PEDV infection. METHODS AND
      RESULTS: Genetically engineered L. casei 393 (L393) strains expressing PEDV COE
      antigen only (pPG-COE/L393) or fused-expressing COE and M cell-targeting peptide
      Co1 (pPG-COE-Co1/L393) were constructed, and the immunogenicity upon
      administration as an oral vaccine was evaluated. The results showed that higher
      anti-PEDV serum IgG and mucosal SIgA antibody responses were induced in mice
      orally immunized with strain pPG-COE-Co1/L393 as compared to the mice immunized
      with strain L393 expressing COE alone or carrying the empty plasmid. In addition,
      the use of the Co1 ligand elicited a splenocyte proliferative response more
      effectively in comparison with the COE antigen alone and supported a skewed T
      helper 2 type of immune response against PEDV. CONCLUSIONS: pPG-COE-Co1/L393 can
      effectively induce mucosal, humoural and Th2-type cellular immune responses
      against PEDV infection via oral administration. Furthermore, M cell-targeting
      peptide ligand Co1 is a good mucosal adjuvant. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Lactobacillus casei delivering the COE antigen of PEDV conjugated with a M
      cell-targeting peptide Co1 as an immune adjuvant is a promising oral vaccine
      candidate for PEDV.

PMID- 29178510
TI  - The pathogenesis of hemodialysis vascular access failure and systemic therapies
      for its prevention: Optimism unfulfilled.
AB  - In patients receiving hemodialysis, the provision of safe and effective vascular
      access using an arteriovenous fistula or graft is regarded as a critical priority
      by patients and health professionals. Vascular access failure is associated with
      morbidity and mortality, such that strategies to prevent these outcomes are
      essential. Inadequate vascular remodeling and neointimal hyperplasia resulting in
      stenosis and frequently thrombosis are critical to the pathogenesis of access
      failure. Systemic medical therapies with pleiotropic effects including
      antiplatelet agents, omega-3 polyunsaturated fatty acids (fish oils), statins,
      and inhibitors of the renin-angiotensin-aldosterone system (RAAS) may reduce
      vascular access failure by promoting vascular access maturation and reducing
      stenosis and thrombosis through antiproliferative, antiaggregatory, anti
      inflammatory and vasodilatory effects. Despite such promise, the results of
      retrospective analyses and randomized controlled trials of these agents on
      arteriovenous fistula and graft outcomes have been mixed. This review describes
      the current understanding of the pathogenesis of arteriovenous fistula and graft
      failure, the biological effects of antiplatelet agents, fish oil supplementation,
      RAAS blockers and statins that may be beneficial in improving vascular access
      survival, results from clinical trials that have investigated the effect of these
      agents on arteriovenous fistula and graft outcomes, and it explores future
      therapeutic approaches combining these agents with novel treatment strategies.

PMID- 29178511
TI  - Neurostimulation for Refractory Cervicogenic Headache: A Three-Year Retrospective
      Study.
AB  - BACKGROUND: Occipital nerve stimulation (ONS) has been used for the treatment of
      neuropathic pain conditions and could be a therapeutic approach for refractory
      cervicogenic headache (CeH). AIM: The aim of this study is to assess the efficacy
      and safety of unilateral ONS in patients suffering from refractory CeH. METHODS:
      We conducted a retrospective chart review on patients implanted from 2011 to 2013
      at CHUM. The primary outcome was a 50% reduction in headache days per month.
      Secondary outcomes included change in EuroQol Group Visual Analog Scale rating of
      health-related quality of life (EQ VAS), six item headache impact test (HIT-6)
      score, hospital anxiety and depression scale (HADS) score, work status, and
      medication overuse. RESULTS: Sixteen patients fulfilled the inclusion criteria;
      they had suffered from daily moderate to severe CeH for a median of 15 years. At
      one year follow-up, 11 patients were responders (69%). There was a statistically
      significant improvement in the EQ VAS score (median change: 40 point increase, p
      = 0.0013) and HIT-6 score (median change: 17.5 point decrease, p = 0.0005).
      Clinically significant anxiety and depression scores both resolved amongst 60% of
      patients. At three years, six patients were responders (37.5%). Out of the 11
      responders at one-year post implantation, five had remained headache responders
      (R-R) and one additional patient became a responder (NR-R). There was a
      statistically significant improvement in the EQ VAS score (median change: 15
      point increase, p = 0.019) and HIT-6 score (median change: 7.5 point decrease, p
      = 0.0017) compared with baseline. Clinically significant anxiety and depression
      scores both, respectively, resolved among 22.5% and 33.9% of patients. Five out
      of seven disabled patients were back to work. CONCLUSION: ONS may be a safe and
      effective treatment modality for patients suffering from a refractory CeH.
      Further study may be warranted.

PMID- 29178512
TI  - Body size and risk of atrial fibrillation: a cohort study of 1.1 million young
      men.
AB  - BACKGROUND: Whilst tall stature has been related to lower risk of vascular
      disease, it has been proposed as a risk factor for atrial fibrillation. Little is
      known about other anthropometric measures and their joint effects on risk of
      atrial fibrillation. OBJECTIVES: We aim to investigate associations and potential
      joint effects of height, weight, body surface area (BSA) and body mass index
      (BMI) with risk of atrial fibrillation. METHODS: In a cohort covering 1 153 151
      18-year-old men participating in the Swedish military conscription (1972-1995),
      Cox regression was used to investigate associations of height, weight, BSA and
      BMI with risk of atrial fibrillation. RESULTS: During a median of 26.3 years of
      follow-up, higher height was associated with higher risk of atrial fibrillation
      (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was
      larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight
      and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI:
      1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative
      joint effect of height and weight. Adjusting for muscle strength, exercise
      capacity and diseases related to atrial fibrillation attenuated these measures.
      CONCLUSIONS: Higher height and weight are strongly associated with higher risk of
      atrial fibrillation. These associations are multiplicative and independent of
      each other and are summarized in a strong association of body surface area with
      risk of atrial fibrillation. The mechanisms remain unknown but may involve
      increased atrial volume load with larger body size.

PMID- 29178513
TI  - Relationship Between Neonatal Vitamin D at Birth and Risk of Autism Spectrum
      Disorders: the NBSIB Study.
AB  - Previous studies suggested that lower vitamin D might be a risk factor for autism
      spectrum disorders (ASDs). The aim of this study was to estimate the prevalence
      of ASDs in 3-year-old Chinese children and to examine the association between
      neonatal vitamin D status and risk of ASDs. We conducted a study of live births
      who had taken part in expanded newborn screening (NBS), with outpatient follow-up
      when the children 3-year old. The children were confirmed for ASDs in outpatient
      by the Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual
      of Mental Disorders (DSM)-5 criteria. Intellectual disability (ID) status was
      defined by the intelligence quotient (IQ < 80) for all the participants. The
      study design included a 1:4 case to control design. The concentration of 25
      hydroxyvitamin D3 [25(OH)D3] in children with ASD and controls were assessed from
      neonatal dried blood samples. A total of 310 children were diagnosed as having
      ASDs; thus, the prevalence was 1.11% (95% CI, 0.99% to 1.23%). The concentration
      of 25(OH)D3 in 310 ASD and 1240 controls were assessed. The median 25(OH)D3 level
      was significantly lower in children with ASD as compared to controls (p <
      0.0001). Compared with the fourth quartiles, the relative risk (RR) of ASDs was
      significantly increased for neonates in each of the three lower quartiles of the
      distribution of 25(OH)D3, and increased risk of ASDs by 260% (RR for lowest
      quartile: 3.6; 95% CI, 1.8 to 7.2; p < 0.001), 150% (RR for second quartile: 2.5;
      95% CI, 1.4 to 3.5; p = 0.024), and 90% (RR for third quartile: 1.9; 95% CI, 1.1
      to 3.3; p = 0.08), respectively. Furthermore, the nonlinear nature of the ID-risk
      relationship was more prominent when the data were assessed in deciles. This
      model predicted the lowest relative risk of ID in the 72rd percentile
      (corresponding to 48.1 nmol/L of 25(OH)D3). Neonatal vitamin D status was
      significantly associated with the risk of ASDs and intellectual disability. The
      nature of those relationships was nonlinear. (c) 2017 American Society for Bone
      and Mineral Research.

PMID- 29178514
TI  - Purely Physisorption-Based CO-Selective Gate-Opening in Microporous Organically
      Pillared Layered Silicates.
AB  - Separation of gas molecules with similar physical and chemical properties is
      challenging but nevertheless highly relevant for chemical processing. By
      introducing the elliptically shaped molecule, 1,4-dimethyl-1,4
      diazabicyclo[2.2.2]octane, into the interlayer space of a layered silicate, a two
      dimensional microporous network with narrow pore size distribution is generated
      (MOPS-5). The regular arrangement of the pillar molecules in MOPS-5 was confirmed
      by the occurrence of a 10 band related to a long-range pseudo-hexagonal
      superstructure of pillar molecules in the interlayer space. Whereas with MOPS-5
      for CO2 adsorption, gate-opening occurs at constant volume by freezing pillar
      rotation, for CO the interlayer space is expanded at gate-opening and a classical
      interdigitated layer type of gate-opening is observed. The selective nature of
      the gate-opening might be used for separation of CO and N2 by pressure swing
      adsorption.

PMID- 29178515
TI  - Visualization of dendritic cells' responses in atopic dermatitis: Preventing
      effect of emollient.
AB  - Atopic dermatitis (AD) is a chronic and multifactorial inflammatory skin disease
      involving various dendritic cells such as epidermal Langerhans cells (LC) and
      inflammatory dendritic epidermal cells (IDECs). Most of the clinical studies was
      performed on isolated cells, and thus, it would be useful to characterize
      directly on the human epidermal tissue the first cellular events occurred during
      the AD. The suction blister method was used to obtain whole epidermis samples and
      interstitial cutaneous fluids. Employing multiphoton microscopy, we analyzed the
      early dynamic behavior of inflammatory cells using Dermatophagoides pteronyssinus
      atopy patch test (Derp-APT) and evaluated the effects of emollient pre
      application. Derp-APT application provoked rapid and strong infiltration of
      IDECs, and proliferation and activation of LC in the AD subjects' epidermis.
      Moreover, emollient pre-application strengthened the defective skin barrier and
      had positive effects on inflammatory cells' behavior, characterized by the
      complete inhibition of IDEC influx and the presence of immature LC.

PMID- 29178516
TI  - Nicotinamide phosphoribosyltransferase delays cellular senescence by upregulating
      SIRT1 activity and antioxidant gene expression in mouse cells.
AB  - Senescent cells accumulate in tissues of aged animals and deteriorate tissue
      functions. The elimination of senescent cells from aged mice not only attenuates
      progression of already established age-related disorders, but also extends median
      lifespan. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting
      enzyme in mammalian NAD+ salvage pathway, has shown a protective effect on
      cellular senescence of human primary cells. However, it still remains unclear how
      NAMPT has a protective impact on aging in vitro and in vivo. In this study, we
      found that primary mouse embryonic fibroblast (MEF) cells undergo progressive
      decline of NAMPT and NAD+ contents during serial passaging before becoming
      senescent. Furthermore, we showed that constitutive Nampt over-expression
      increases cellular NAD+ content and delays cellular senescence of MEF cells in
      vitro. We further found that constitutive Nampt over-expression increases SIRT1
      activity, increases the expression of antioxidant genes, superoxide dismutase 2
      and catalase and promotes resistance against oxidative stress. These findings
      suggest that Nampt over-expression in MEF cells delays cellular senescence by the
      mitigation of oxidative stress via the upregulation of superoxide dismutase 2 and
      catalase gene expressions by SIRT1 activation.

PMID- 29178517
TI  - Women's attractiveness is linked to expected age at menopause.
AB  - A great number of studies have shown that features linked to immediate fertility
      explain a large part of the variance in female attractiveness. This is consistent
      with an evolutionary perspective, as men are expected to prefer females at the
      age at which fertility peaks (at least for short-term relationships) in order to
      increase their reproductive success. However, for long-term relationships, a high
      residual reproductive value (the expected future reproductive output, linked to
      age at menopause) becomes relevant as well. In that case, young age and late
      menopause are expected to be preferred by men. However, the extent to which
      facial features provide cues to the likely age at menopause has never been
      investigated so far. Here, we show that expected age at menopause is linked to
      facial attractiveness of young women. As age at menopause is heritable, we used
      the mother's age at menopause as a proxy for her daughter's expected age of
      menopause. We found that men judged faces of women with a later expected age at
      menopause as more attractive than those of women with an earlier expected age at
      menopause. This result holds when age, cues of immediate fertility and facial
      ageing were controlled for. Additionally, we found that the expected age at
      menopause was not correlated with any of the other variables considered
      (including immediate fertility cues and facial ageing). Our results show the
      existence of a new correlate of women's facial attractiveness, expected age at
      menopause, which is independent of immediate fertility cues and facial ageing.

PMID- 29178518
TI  - Low annual frequency of HbA1c testing in people with Type 2 diabetes in primary
      care practices in Germany.
AB  - AIMS: To analyse the annual frequency of HbA1c testing, as well as the factors
      associated with higher or lower testing frequency, in people with Type 2 diabetes
      mellitus in general practices and specialist diabetes practices in Germany.
      METHODS: A total of 43 509 people diagnosed with Type 2 diabetes between January
      2016 and December 2016 in 557 medical practices (51% of all practices) were
      included in this study. The primary outcome was the annual recorded frequency of
      HbA1c testing in 2016. Multivariable logistic regression analyses were performed
      to identify variables associated with the odds of HbA1c concentration being
      tested at least twice in 2016, using predefined demographic and clinical
      variables. RESULTS: The mean (sd) number of reported HbA1c tests was 2.7 (1.6) in
      2016. Overall, 74% of individuals had at least two annual HbA1c measurements. The
      likelihood of receiving >=2 HbA1c tests was inversely associated with stroke
      (odds ratio 0.81, 95% CI 0.74-0.89), shorter diabetes duration (<=1 year: odds
      ratio 0.77, 95% CI 0.70-0.84) and higher mean HbA1c concentration (>=8.5%: odds
      ratio 0.85, 95% CI 0.76-0.94) and was positively associated with specialist
      diabetes care (odds ratio 1.24, 95% CI 1.14-1.36), hypertension (odds ratio 1.10,
      95% CI 1.04-1.17), hyperlipidaemia (odds ratio 1.48, 95% CI 1.41 to 1.55), renal
      complications (odds ratio 1.41, 95% CI 1.32 to 1.50), neuropathy (odds ratio
      1.27, CI 1.20 to 1.35) and retinopathy (odds ratio 1.38, 95% CI 1.25 to 1.52).
      CONCLUSIONS: Only three out of four individuals with Type 2 diabetes underwent at
      least two HbA1c tests in Germany in 2016, which means that 25% of individuals
      underwent fewer tests than required by German guidelines.

PMID- 29178519
TI  - Semaglutide, reduction in glycated haemoglobin and the risk of diabetic
      retinopathy.
AB  - AIMS: To evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical
      trial programme. MATERIALS AND METHODS: The SUSTAIN clinical trial programme
      evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1
      analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2-year, pre
      approval cardiovascular outcomes trial, semaglutide was associated with a
      significant increase in the risk of DR complications (DRC) vs placebo. DR data
      from across the SUSTAIN trials were evaluated, and post hoc analyses of the
      SUSTAIN 6 data were conducted. These included subgroup analyses to identify at
      risk patients and a mediation analysis with initial change in glycated
      haemoglobin (HbA1c; percentage-points at week 16) as a covariate, to examine the
      role of the magnitude of reduction in HbA1c as an intermediate factor affecting
      risk of DRC. RESULTS: There was no imbalance in DR adverse events across the
      SUSTAIN 1 to 5 and Japanese trials. The majority of the effect with semaglutide
      vs placebo in SUSTAIN 6 may be attributed to the magnitude and rapidity of HbA1c
      reduction during the first 16 weeks of treatment in patients who had pre-existing
      DR and poor glycaemic control at baseline, and who were treated with insulin.
      CONCLUSIONS: Early worsening of DR is a known phenomenon associated with the
      rapidity and magnitude of improvement in glycaemic control with insulin; the DRC
      findings in SUSTAIN 6 are consistent with this. Guidance regarding the early
      worsening of DR is recommended with insulin. Similar recommendations may be
      appropriate for semaglutide.

PMID- 29178520
TI  - A catch-22: Interleukin-22 and cancer.
AB  - Barrier surfaces of multicellular organisms are in constant contact with the
      environment and infractions to the integrity of epithelial surfaces is likely a
      frequent event. Interestingly, components of the immune system, that can be
      activated by environmental compounds such as the microbiota or nutrients, are
      interspersed among epithelial cells or directly underlie the epithelium. It is
      now appreciated that immune cells continuously receive and integrate signals from
      the environment. Curiously, such continuous reception of stimulation does not
      normally trigger an inflammatory response but mediators produced by immune cells
      in response to such signals seem to rather promote barrier integrity and repair.
      The molecular mediators involved in this process are poorly understood. In recent
      years, the cytokine interleukin-22, produced mainly by group 3 innate lymphoid
      cells (ILCs), has been studied as a paradigm for how immune cells can control
      various aspects of epithelial cell function because expression of its receptor is
      restricted to non-hematopoietic cells. We will summarize here the diverse roles
      of IL-22 for the malignant transformation of epithelial cells, for tumor growth,
      wound healing and tissue repair. Furthermore, we will discuss IL-22 as a
      potential therapeutic target.

PMID- 29178521
TI  - Multiple Routes to Smart Nanostructured Materials from Diatom Microalgae: A
      Chemical Perspective.
AB  - Diatoms are unicellular photosynthetic microalgae, ubiquitously diffused in both
      marine and freshwater environments, which exist worldwide with more than 100 000
      species, each with different morphologies and dimensions, but typically ranging
      from 10 to 200 um. A special feature of diatoms is their production of siliceous
      micro- to nanoporous cell walls, the frustules, whose hierarchical organization
      of silica layers produces extraordinarily intricate pore patterns. Due to the
      high surface area, mechanical resistance, unique optical features, and
      biocompatibility, a number of applications of diatom frustules have been
      investigated in photonics, sensing, optoelectronics, biomedicine, and energy
      conversion and storage. Current progress in diatom-based nanotechnology relies
      primarily on the availability of various strategies to isolate frustules,
      retaining their morphological features, and modify their chemical composition for
      applications that are not restricted to those of the bare biosilica produced by
      diatoms. Chemical or biological methods that decorate, integrate, convert, or
      mimic diatoms' biosilica shells while preserving their structural features
      represent powerful tools in developing scalable, low-cost routes to a wide
      variety of nanostructured smart materials. Here, the different approaches to
      chemical modification as the basis for the description of applications relating
      to the different materials thus obtained are presented.

PMID- 29178522
TI  - Direct hyperbilirubinemia in infants with congenital heart disease.
AB  - BACKGROUND: The association between congenital heart disease (CHD) and infantile
      cholestasis, a key finding for the diagnosis of biliary atresia (BA), has not
      been previously investigated. The aim of this study was therefore to investigate
      the characteristics of direct hyperbilirubinemia (D-HB) in infants with CHD.
      METHODS: All neonates admitted to the present hospital and diagnosed with CHD in
      2015 and 2016 were included. D-HB (direct bilirubin >= 2.0 mg/dL) at <=60 days of
      age and other clinical parameters were retrospectively reviewed. Statistical
      analysis according to presence of D-HB was performed using chi-squared test or
      Wilcoxon rank sum test. RESULTS: Seventy-six patients (M:F, 36:40) were included
      in this study. CHD consisted of ventricular septal defect in 17, patent ductus
      arteriosus in 10, and other in 49. Thirteen patients (17.1%) had D-HB at <=60
      days of age. Resolution of D-HB (DB < 2.0 mg/dL) occurred in 10 of the 13
      patients during the hospital stay, and this occurred in <=7 days in eight of the
      10 patients. Sex, gestational age, birthweight, chromosomal anomalies, need for
      Fontan operation for CHD repair, and/or cardiac operation were not associated
      with D-HB at <=60 days of age. CONCLUSION: While D-HB was frequently observed in
      infants with CHD, the majority of D-HB cases resolved spontaneously in <=1 week.
      Neonatal clinical parameters or CHD status was not predictive of D-HB. D-HB
      lasting >1 week in infants with CHD should be evaluated for the cause.

PMID- 29178523
TI  - Acute intraventricular conduction disorder due to combination therapy with
      dabrafenib and trametinib for metastatic melanoma: Case report.

PMID- 29178524
TI  - Exposure to Trauma and Mental Health Service Engagement Among Adults Who Were
      Children of the Northern Ireland Troubles of 1968 to 1998.
AB  - Northern Ireland is an appropriate region to examine the impact of traumatic
      experiences, owing to the many years of civil violence that have characterized
      its recent history, known colloquially as the "Troubles." Given the prominence of
      traumatic experiences among the aging population of Northern Ireland (NI), an
      evidence base is required to inform the planning and provision of effective
      mental health and other services. We analyzed the follow-up interviews (n = 225)
      of individuals from the Northern Ireland Study of Health and Stress (NISHS), aged
      45 years and older, who experienced one or more conflict-related traumatic
      events. This study demonstrated that in NI traumatic events, such as being
      involved in an explosion, seeing someone killed or seriously injured, and living
      in a region of terror were most likely to be related to the Troubles. However,
      event types that we had not previously known to be related to conflict (such as
      the sudden death of a loved one), were also often related to the Troubles. Two
      thirds of participants (67.1%) reported exposure to a Troubles-related event, and
      57.8% reported being a civilian in a region of terror. The vast majority (85.9%)
      of participants who experienced a Troubles-related trauma never sought help,
      despite 59.1% meeting the criteria for a lifetime mental disorder. The reasons
      for not seeking help and sources of help are outlined. Policy makers must address
      Troubles-related mental health effects, in terms of how they carry forward into
      aging, and consider ways of improving engagement with services and treatments.

PMID- 29178525
TI  - Flow dynamics of cerebrospinal fluid between the intracranial cavity and the
      subarachnoid space of the optic nerve measured with a diffusion magnetic
      resonance imaging sequence in patients with normal tension glaucoma.
AB  - IMPORTANCE: This study offers a new approach for the quantification of CSF
      dynamics. BACKGROUND: Non-invasive method to quantify the CSF dynamics in the
      subarachnoid space of the optic nerve is highly desirable. The aim of the study
      was to measure slow-flow CSF velocities in healthy controls and normal tension
      glaucoma patients between the intracranial cavity and the subarachnoid space of
      the optic nerve. DESIGN: Prospective observational study. PARTICIPANTS: Eleven
      age-matched healthy volunteers and 15 normal tension glaucoma patients. METHODS:
      Using phase contrast images, the phase shift in MRI diffusion images can be used
      to determine the flow velocity. Flow-range ratio between the intracranial cavity
      and the subarachnoid space of the optic nerve was calculated. MAIN OUTCOME
      MEASURE: Flow-range ratio between the intracranial cavity and the subarachnoid
      space of the optic nerve was calculated. RESULTS: First, phantom measurements
      were provided to validate the slow-flow velocity calculations. Second, flow-range
      ratio was validated for the healthy controls (0.63 +/- 0.05), with the range
      being similar for the right and left optic nerve (P = 0.1). Statistically
      significant results were obtained (P < 0.05) when comparing the flow-range ratio
      in the optic nerve of healthy controls (n = 22 eyes, 0.63 +/- 0.05) with the flow
      range ratio in pathological optic nerves (n = 23, 0.55 +/- 0.08) of normal
      tension glaucoma patients. MANOVA revealed no dependency between flow-range ratio
      and patient dependent variables. CONCLUSION AND RELEVANCE: Diffusion-weighted
      imaging provides a method to evaluate CSF flow within the subarachnoid space of
      the optic nerve in a non-invasive manner. Compared to healthy controls, patients
      with normal tension glaucoma measure a significantly lower flow-range ratio. This
      finding suggests a possible role of impaired CSF dynamics in the pathophysiology
      in normal tension glaucoma.

PMID- 29178526
TI  - Rapid characterization of nonpolar or low-polarity solvent extracts from herbal
      medicines by solvent-assisted electrospray ionization mass spectrometry.
AB  - RATIONALE: The direct detection of nonpolar and low-polarity solvent extracts of
      herbal medicine is difficult by conventional electrospray ionization mass
      spectrometry (ESI-MS). This problem can be solved by solvent-assisted
      electrospray ionization mass spectrometry (SAESI-MS). With the help of assisted
      solvents (ESI-friendly solvents) at the tip of the spray needle, compounds
      (especially the low-polarity compounds) in nonpolar and low-polarity solvent
      extracts can be ionized directly. METHODS: Herbal medicines were ultrasonically
      extracted with nonpolar or low-polarity solvents, such as petroleum ether.
      Thereafter, the extracts were analyzed by conventional ESI-MS, atmospheric
      pressure chemical ionization mass spectrometry (APCI-MS) and SAESI-MS. The mass
      spectra obtained from these three methods were compared and analyzed. RESULTS:
      Unstable ion signals, and even no ion signals, were observed when the nonpolar
      and low-polarity solvent extracts were detected directly by conventional ESI-MS.
      Better specificity, higher sensitivity or cleaner spectra were acquired from
      SAESI-MS by comparing with the performance of conventional ESI-MS. The ion
      signals generated by SAESI-MS and APCI-MS were observed in clearly different m/z
      ranges. A variety of potential compounds were detected in the petroleum ether
      extracts of Pogostemon cablin and Ligusticum chuanxiong. The relative abundances
      and signal intensities of the same ion signals from the stems, leaves and
      decoction pieces of Pogostemon cablin were significantly different by SAESI-MS.
      CONCLUSIONS: As a convenient and efficient method, SAESI-MS can be used to
      directly detect compounds (especially the low-polarity compounds) in nonpolar or
      low-polarity solvent extracts of herbal medicines, providing abundant chemical
      information for pharmacological studies. SAESI-MS allows the simultaneous
      qualitative analysis of multiple compounds in the same complex samples and is
      thus particularly suitable for the preliminary screening of compounds in complex
      samples. SAESI-MS can be used to differentiate the different parts of herbal
      medicines.

PMID- 29178527
TI  - Reconstruction of elbow skin and soft tissue defects using perforator-pedicled
      propeller flaps.
AB  - BACKGROUND: The elbow is a challenging region to reconstruct functionally.
      Several closure methods for elbow wounds have been reported, including flap
      surgery. Here, we present the results obtained using a propeller flap pedicled by
      a posterior ulnar recurrence artery perforator (PURAP) or a radial collateral
      artery perforator (RCAP) for functional reconstruction of soft tissue defects in
      elbows. METHODS: Twenty-four patients with an average age of 27.0 years (range, 9
      52 years) underwent elbow soft tissue reconstructions between 2005 and 2015.
      Twenty-one patients were male and three were female. Among them, 18 patients
      received a PURAP flap transfer and six received a RCAP flap transfer. The
      frequent soft tissue defects were due to release of a postburn scar contracture
      in 12 patients, trauma in ten patients. Functional results were obtained by
      measuring range of motion (ROM). RESULTS: The mean follow up time was 10.1 months
      (range, 4-22 months). The flaps ranged in size from 3 * 5 cm to 16 * 6 cm. Nearly
      all flaps survived with only one showing partial necrosis. 16 and 8 patients
      achieved ranges of motions of 0-5 and 6-15 degree extension and 130-145 degree
      flexion. CONCLUSIONS: With the aims of easy flap harvest, primary donor site
      closure, skin texture match, and avoiding vascular anastomosis, both PURAP and
      RCAP were employed. Both flap transfer techniques were safe and effective for
      elbow soft tissue reconstruction. It is important to ensure that the skin defect
      and flap design are closely matched.

PMID- 29178528
TI  - Nanoscale Chemical Imaging of Reversible Photoisomerization of an Azobenzene
      Thiol Self-Assembled Monolayer by Tip-Enhanced Raman Spectroscopy.
AB  - An understanding of the photoisomerization mechanism of molecules bound to a
      metal surface at the molecular scale is required for designing photoswitches at
      surfaces. It has remained a challenge to correlate the surface structure and
      isomerization of photoswitches at ambient conditions. Herein, the
      photoisomerization of a self-assembled monolayer of azobenzene-thiol molecules on
      a Au surface was investigated using scanning tunneling microscopy and tip
      enhanced Raman spectroscopy. The unique signature of the cis isomer at 1525 cm-1
      observed in tip-enhanced Raman spectra was clearly distinct from the trans
      isomer. Furthermore, tip-enhanced Raman images of azobenzene thiols after
      ultraviolet and blue light irradiation are shown with nanoscale spatial
      resolution, demonstrating a reversible conformational change. Interestingly, the
      cis isomers of azobenzene-thiol molecules were preferentially observed at Au
      grain edges, which is confirmed by density functional theory.

PMID- 29178529
TI  - Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women
      and in men - short version.
AB  - Androgenetic alopecia is the most common hair loss disorder, affecting both men
      and women. Initial signs of androgenetic alopecia usually develop during teenage
      years leading to progressive hair loss with a pattern distribution. Moreover, its
      frequency increases with age and affects up to 80% Caucasian men and 42% of
      women. Patients afflicted with androgenetic alopecia may undergo significant
      impairment of quality of life. The European Dermatology Forum (EDF) initiated a
      project to develop evidence-based guidelines for the treatment of androgenetic
      alopecia. Based on a systematic literature research the efficacy of the currently
      available therapeutic options was assessed and therapeutic recommendations were
      passed in a consensus conference. The purpose of the guideline is to provide
      dermatologists with an evidence-based tool for choosing an efficacious and safe
      therapy for patients with androgenetic alopecia.

PMID- 29178530
TI  - Photoluminescent properties of Eu3+ -Eu2+ activated MAl2 Six O2x + 4 (M = Mg, Ca,
      Sr, Ba) phosphors prepared in air.
AB  - In this paper, MAl2 Six O2x+4 :Eu2+ /Eu3+ (Eu2+ + Eu3+ = 2%, molar ratio; M = Mg,
      Ca, Sr, Ba; x = 0, 0.5, 1, 1.5, 2) phosphors with different SiO2 concentrations
      (the ratio of SiO2 to MAl2 O4 is n%, n = 0, 50, 100, 150, 200, respectively) were
      prepared by high-temperature solid-state reaction under atmospheric air
      conditions. Their structures and photoluminescent properties were systematically
      researched. The results indicate that Eu3+ ions have been reduced and Eu2+ ions
      are obtained in air through the self-reduction mechanism. The alkaline earth
      metal ions and doping SiO2 strongly affect the crystalline phase and
      photoluminescent properties of samples, including microstructures, relative
      intensity of Eu2+ to Eu3+ , location of emission lines/bands. It is interesting
      and important that the emission color and intensities of europium-doped various
      phosphors which consist of aluminosilicate matrices prepared under atmospheric
      air conditions could be modulated by changing the kinds of alkaline earth metal
      and the content of SiO2 .

PMID- 29178531
TI  - Vertical vs. horizontal transmission of the microbiome in a key disease vector,
      Ixodes pacificus.
AB  - Vector-borne pathogens are increasingly found to interact with the vector's
      microbiome, influencing disease transmission dynamics. However, the processes
      that regulate the formation and development of the microbiome are largely
      unexplored for most tick species, an emerging group of disease vectors. It is not
      known how much of the tick microbiome is acquired through vertical transmission
      vs. horizontally from the environment or interactions with bloodmeal sources.
      Using 16S rRNA sequencing, we examined the microbiome of Ixodes pacificus, the
      vector of Lyme disease in the western USA, across life stages and infection
      status. We also characterized microbiome diversity in field and laboratory
      collected nymphal ticks to determine how the surrounding environment affects
      microbiome diversity. We found a decrease in both species richness and evenness
      as the tick matures from larva to adult. When the dominant Rickettsial
      endosymbiont was computationally removed from the tick microbial community, we
      found that infected nymphs had lower species evenness than uninfected ticks,
      suggesting that lower microbiome diversity is associated with pathogen
      transmission in wild-type ticks. Furthermore, laboratory-reared nymph microbiome
      diversity was found to be compositionally distinct and significantly depauperate
      relative to field-collected nymphs. These results highlight unique patterns in
      the microbial community of I. pacificus that is distinct from other tick species.
      We provide strong evidence that ticks acquire a significant portion of their
      microbiome through exposure to their environment despite a loss of overall
      diversity through life stages. We provide evidence that loss of microbial
      diversity is at least in part due to elimination of microbial diversity with
      bloodmeal feeding but other factors may also play a role.

PMID- 29178532
TI  - Microfluidics Based Point-of-Care Diagnostics.
AB  - Point-of-care (POC) diagnostic devices have been predicted to provide a boon in
      health care especially in the diagnosis and detection of diseases. POC devices
      have been found to have many advantages like a rapid and precise response,
      portability, low cost, and non-requirement of specialized equipment. The major
      objective of a POC diagnostic research is to develop a chip-based, self
      containing miniaturized device that can be used to examine different analytes in
      complex samples. Further, the integration of microfluidics (MF) with advanced
      biosensor technologies is likely to result in improved POC diagnostics. This
      paper presents the overview of the different materials (glass, silicon, polymer,
      paper) and techniques for the fabrication of MF based POC devices along with
      their wide range of biosensor applications. Besides this, the authors have
      presented in brief the challenges that MF is currently facing along with possible
      solutions that may result in the availability of the accessible, reliable, and
      cost-efficient technology. The development of these devices requires the
      combination of developed MF components into POC devices that are user-friendly,
      sensitive, stable, accurate, low cost, and minimally invasive. These MF based POC
      devices have tremendous potential in providing improved healthcare including easy
      monitoring, early detection of disease, and increased personalization.

PMID- 29178533
TI  - Urethral Complications After Transgender Phalloplasty: Strategies to Treat Them
      and Minimize Their Occurrence.
AB  - Radial forearm free flap phalloplasty (RFFP) is the current standard of care for
      most FTM gender confirmation surgeries. This procedure is associated with a rate
      of urethral stricture as high as 51%, which falls only to 23-35% even among the
      most experienced contemporary surgeons. While some modifications have been
      proposed to combat this high complication rate, it still remains a major source
      of lasting morbidity. The method involves literature review of RFFP literature.
      Lowest stricture rates are found when neourethra is made with a long,
      meticulously constructed tube of well-vascularized perivaginal/periurethral and
      labia minora tissue. In cases of urethral stricture, urethroplasty is required in
      94-96% of patients. Surgery should be delayed until all acute inflammation has
      subsided. Urethroplasty is technically challenging and fails in up to 50% of
      cases. Repeated surgery or salvage urethral exteriorization procedures, which can
      leave the patient with lifelong perineal urethrostomy, are often required.
      Patient and physician knowledge regarding the high burden and poor treatment
      options for urethral stricture after phalloplasty is incomplete, and patient
      acceptance of this reality is crucial for honest understanding of the potential
      complications of this increasingly common but extremely complex surgery. Clin.
      Anat. 31:187-190, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29178534
TI  - Immune Checkpoint PD-1/PD-L1: Is There Life Beyond Antibodies?
AB  - The PD-1/PD-L1 interaction has emerged as a significant target in cancer
      immunotherapy. Current medications include monoclonal antibodies, which have
      shown impressive clinical results in the treatment of several types of tumors.
      The cocrystal structure of human PD-1 and PD-L1 is expected to be a valuable
      starting point for the design of novel inhibitors, along with the recent crystal
      structures with monoclonal antibodies, small molecules, and macrocycles.

PMID- 29178535
TI  - Peritraumatic Assessment of Autobiographical Memory After Exposure to a Traumatic
      Event.
AB  - Posttraumatic stress disorder (PTSD) is commonly acknowledged to be associated
      with reduced specificity of autobiographical memory (AM). However, very few
      studies have assessed AM in the peritraumatic phase. The aim of the present study
      was to examine whether the AM impairment reported in PTSD is present a few days
      after a traumatic event. We assessed AM in 41 participants who had recently been
      exposed to trauma, and 34 controls who had never experienced a traumatic
      situation. The trauma-exposed participants also completed the Impact of Event
      Scale-R (IES-R), the Inventory of Peritraumatic Distress, and the Peritraumatic
      Dissociative Experiences Questionnaire. Results showed that autobiographical
      memories cued by negative words were significantly less specific in the group of
      trauma-exposed participants than in the control group (p = .008; d = 0.40). Thus,
      mild AM impairment was already present three days after trauma exposure, long
      before acute PTSD set in.

PMID- 29178536
TI  - Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low
      saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A
      2-year randomized clinical trial.
AB  - AIM: To examine whether a low-carbohydrate, high-unsaturated/low-saturated fat
      diet (LC) improves glycaemic control and cardiovascular disease (CVD) risk
      factors in overweight and obese patients with type 2 diabetes (T2D). METHODS: A
      total of 115 adults with T2D (mean [SD]; BMI, 34.6 [4.3] kg/m2 ; age, 58 [7]
      years; HbA1c, 7.3 [1.1]%) were randomized to 1 of 2 planned energy-matched,
      hypocaloric diets combined with aerobic/resistance exercise (1 hour, 3 days/week)
      for 2 years: LC: 14% energy as carbohydrate, 28% as protein, 58% as fat (<10%
      saturated fat); or low-fat, high-carbohydrate, low-glycaemic index diet (HC): 53%
      as CHO, 17% as protein, 30% as fat (<10% saturated fat). HbA1c, glycaemic
      variability (GV), anti-glycaemic medication effect score (MES, calculated based
      on the potency and dosage of diabetes medication), weight, body composition, CVD
      and renal risk markers were assessed before and after intervention. RESULTS: A
      total of 61 (LC = 33, HC = 28) participants completed the study (trial
      registration: http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820).
      Reductions in weight (estimated marginal mean [95% CI]; LC, -6.8 [-8.8,-4.7], HC,
      -6.6 [-8.8, -4.5] kg), body fat (LC, -4.3 [-6.2, -2.4], HC, -4.6 [-6.6, -2.7]
      kg), blood pressure (LC, -2.0 [-5.9, 1.8]/ -1.2 [-3.6, 1.2], HC, -3.2 [-7.3,
      0.9]/ -2.0 [-4.5, 0.5] mmHg), HbA1c (LC, -0.6 [-0.9, -0.3], HC, -0.9 [-1.2, -0.5]
      %) and fasting glucose (LC, 0.3 [-0.4, 1.0], HC, -0.4 [-1.1, 0.4] mmol/L) were
      similar between groups (P >= 0.09). Compared to HC, the LC achieved greater
      reductions in diabetes medication use (MES; LC, -0.5 [-0.6, -0.3], HC, -0.2 [
      0.4, -0.02] units; P = 0.03), GV (Continuous Overall Net Glycemic Action
      calculated every 1 hour (LC, -0.4 [-0.6, -0.3], HC, -0.1 [-0.1, 0.2] mmol/L; P =
      0.001), and 4 hours (LC, -0.9 [-1.3, -0.6], HC, -0.2 [-0.6, 0.1] mmol/L; P =
      0.02)); triglycerides (LC, -0.1 [-0.3, 0.2], HC, 0.1 [-0.2, 0.3] mmol/L; P =
      0.001), and maintained HDL-C levels (LC, 0.02 [-0.05, 0.1], HC, -0.1 [-0.1, 0.01]
      mmol/L; P = 0.004), but had similar changes in LDL-C (LC, 0.2 [-0.1, 0.5], HC,
      0.1 [-0.2, 0.4] mmol/L; P = 0.85), brachial artery flow mediated dilatation (LC, 
      0.5 [-1.5, 0.5], HC, -0.4 [-1.4, 0.7] %; P = 0.73), eGFR and albuminuria.
      CONCLUSIONS: Both diets achieved comparable weight loss and HbA1c reductions. The
      LC sustained greater reductions in diabetes medication requirements, and in
      improvements in diurnal blood glucose stability and blood lipid profile, with no
      adverse renal effects, suggesting greater optimization of T2D management.

PMID- 29178538
TI  - Evidence for Itinerant Carriers in an Anisotropic Narrow-Gap Semiconductor by
      Angle-Resolved Photoemission Spectroscopy.
AB  - The ability to accurately determine the electronic structure of solids has become
      a key prerequisite for modern functional materials. For example, the precise
      determination of the electronic structure helps to balance the three
      thermoelectric parameters, which is the biggest challenge to design high
      performance thermoelectric materials. Herein, by high-resolution, angle-resolved
      photoemission spectroscopy (ARPES), the itinerant carriers in CsBi4 Te6 (CBT) are
      revealed for the first time. CBT is a typical anisotropic, narrow-gap
      semiconductor used as a practical candidate for low-temperature thermoelectric
      applications, and p-doped CBT series show superconductivity at relatively low
      carrier concentrations. The ARPES results show a significantly larger bandwidth
      near the Fermi surface than calculations, which means the carriers transport
      anisotropically and itinerantly in CBT. It is reasonable to believe that these
      newly discovered features of carriers in narrow-gap semiconductors are promising
      for designing optimal thermoelectric materials and superconductors.

PMID- 29178537
TI  - Chemical Composition and In vitro Anthelmintic Activity of Extracts of Tagetes
      patula Against a Multidrug-Resistant Isolate of Haemonchus contortus.
AB  - Sheep breeding has suffered economic losses due to parasitism by gastrointestinal
      nematodes, particularly Haemonchus contortus. The use of natural products,
      specifically Tagetes patula, has been suggested as an alternative method of
      combatting this issue. Chemical analyses of the extracts of this species
      described in the literature report the presence of important classes of secondary
      metabolites such as thiophenes, flavonoids, alkaloids, and benzofurans, some of
      which were identified and isolated in this study. The aim of this work was to
      test the effect of the essential oil (EO) and the ethanolic extract of the aerial
      parts (TpEtOH ) of T. patula on eggs and larvae of H. contortus, through an egg
      hatch test (EHT) and a larval development test (LDT). In the EHT, the EO showed
      100% inhibition at 0.75 mg mL-1 (LC50 = 0.0780 mg mL-1 ), and the TpEtOH showed
      100% inhibition at 100 mg mL-1 (LC50 = 12.8 mg mL-1 ). In the LDT, the EO showed
      100% inhibition at 0.375 mg mL-1 (LC50 = 0.0400 mg mL-1 ), and the TpEtOH showed
      100% inhibition at 1.56 mg mL-1 (LC50 = 0.340 mg mL-1 ). Compared to available
      literature data, the results presented here suggest that the crude extracts of T.
      patula have substantial potential for controlling this nematode by interrupting
      its life cycle and/or preventing it from reaching the infective stage.

PMID- 29178539
TI  - Non-melanoma Hutchinson's sign: a reappraisal of this important, remarkable
      melanoma simulant.
AB  - BACKGROUND: More than 20 years ago, our reappraisal of the Hutchinson's sign (HS)
      gave birth to the concept of the pseudo-Hutchinson's sign. OBJECTIVES: We have
      found it interesting to emphasize some important histologic points and to expand
      the list of the numerous HS simulants. METHODS: We have examined the cutaneous
      samples taken from the pigmented skin of patients in association with nail matrix
      biopsy. We have also extended the long list of non-melanoma HS based on
      comprehensive literature review. RESULTS: Histologically, HS may present only as
      an epidermal pigmentation, depending on the area sampled. Occasionally, there may
      be a sparse junctional melanocytic proliferation which does not demonstrate
      cytologic atypia due to an underlying melanocytic naevus of the nail matrix.
      However, early HS often shows a melanoma in situ, with a HS at the proximal nail
      fold (PNF) and confluent "atypical" melanocytes in the nail matrix. Finally,
      involvement of the PNF, nail matrix and nail bed containing atypical melanocytes
      in irregular array may be seen in more advanced lesions. The recent literature on
      non-melanoma HS simulants is summarized and clinical examples are provided.
      CONCLUSION: The mere presence of periungual pigmentation is neither clinically
      nor histologically pathognomonic of subungual melanoma and justifies the
      usefulness of this work stressing the non-melanoma HS.

PMID- 29178540
TI  - Can time to failure predict the faulty component in artificial urinary sphincter
      device malfunctions?
AB  - OBJECTIVE: Artificial urinary sphincter malfunctions can occur in any of the
      individual components. Preoperative identification of the malfunctioning
      component can be valuable for patient counseling and surgical planning. The
      optimal strategy for repair of failed artificial urinary sphincter components is
      debated given the relative rarity of the situation. The aim of the present study
      was to evaluate the relationship of time to failure with failed artificial
      urinary sphincter component and to compare our outcomes of specific component
      versus complete device replacement. METHODS: From 1983 to 2011, 1805 artificial
      urinary sphincter procedures were carried out at Mayo Clinic (Rochester,
      Minnesota, USA), of which 1072 patients underwent primary artificial urinary
      sphincter placement. Clinical variables, including time to failure, were
      evaluated for association with component failure. Bootstrap analysis was used to
      estimate the differences in time to reach a fixed percentage of component
      failure. RESULTS: A total of 115 patients experienced device failure at a median
      follow up of 4.2 years. Urethral cuff, abdominal reservoir, scrotal pump and
      tubing malfunction occurred in 53 (4.9%), 26 (2.4%), 11 (1%) and 25 (2.3%)
      patients, respectively. Increasing age at the time of primary surgery was
      protective of cuff malfunction (hazard ratio 0.97, P = 0.04). Time to 3% urethral
      cuff failure outpaced other component failures (P < 0.05). Secondary failure-free
      rates after whole device versus specific component revisions were comparable (P =
      0.38). CONCLUSIONS: Clinical predictors for artificial urinary sphincter failure
      continue to be difficult to establish. Although single component versus entire
      device replacement have similar outcomes, if pursuing single component revision,
      we recommend cuff-first interrogation in devices in place for >3 years, as this
      represents the most likely component to fail.

PMID- 29178541
TI  - Violence against emergency medical services personnel: A systematic review of the
      literature.
AB  - BACKGROUND: Violence against emergency medical services (EMS) personnel is a
      growing concern. The aim of this systematic review is to synthesize the current
      literature on violence against EMS personnel. METHODS: We examined literature
      from 2000 to 2016. Eligibility criteria included English-language, peer-reviewed
      studies of EMS personnel that described violence or assaults. Sixteen searches
      identified 2655 studies; 25 studies from nine countries met the inclusion
      criteria. RESULTS: The evidence from this review demonstrates that violence is a
      common risk for EMS personnel. We identified three critical topic areas: changes
      in risk over time, economic impact of violence and, outcomes of risk-reduction
      interventions. There is a lack of peer reviewed research of interventions, with
      the result that current intervention programs have no reliable evidence base.
      CONCLUSIONS: EMS leaders and personnel should work together with researchers to
      design, implement, evaluate and publish intervention studies designed to mitigate
      risks of violence to EMS personnel.

PMID- 29178542
TI  - E-selectin gene in essential hypertension: a case-control study.
AB  - BACKGROUND: Hypertension is associated with endothelial cell dysfunction. E
      selectin, an endothelial cell adhesion molecule, is specific for endothelial cell
      activation. Polymorphism in E-selectin gene has recently been identified among
      which Leu554Phe E-selectin gene polymorphism is least investigated in essential
      hypertension. This study reports the association of E-selectin gene Leu554Phe
      polymorphism and the expression of E-selectin gene in patients with essential
      hypertension. MATERIALS AND METHODS: We analysed the Leu554Phe polymorphism and
      expression of E-selectin gene in 250 patients with essential hypertension and 250
      normal healthy controls. Genotyping of Leu554Phe polymorphism was performed by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),
      and the expression of E-selectin gene at mRNA and protein levels were carried out
      by real-time PCR and Western blot, respectively. RESULTS: A significant
      association of E-selectin genotypes (CT + TT) with essential hypertension (P <
      .0001, Odds ratio = 2.2 [1.58-3.24] at 95% CI) was observed. The expression of
      mRNA for E-selectin gene in patients with essential hypertension was ~12-fold
      higher as compared to control. We observed an elevated level of E-selectin
      protein expression (up to 1.9 times) in patients as compared to controls.
      CONCLUSIONS: A significant association of E-selectin (Leu554Phe) gene and
      increased expression of E-selectin gene at mRNA and protein levels in patients
      might be related to the genetic predisposition to develop essential hypertension.

PMID- 29178543
TI  - Neovaginal Construction with Pelvic Peritoneum: Reviewing an Old Approach for a
      New Application.
AB  - Transgender reassignment surgeries have become a major topic of interest within
      the last decade. Although there are numerous surgical techniques for male-to
      female reassignment, a physician must assess each patient's anatomy and past
      medical history to determine the most suitable technique. Additionally, patient
      preference is important. The neovaginal constructive technique most commonly used
      in male-to-female reassignment surgery is penile skin inversion, but various
      other techniques and tissues can also be used including pelvic peritoneum, buccal
      mucosa, and bowel. Surgical text descriptions were enhanced by creating new
      anatomical illustrations. Donor and recipient site anatomies, and the surgical
      technique leading to creation of the neovagina, are demonstrated in detail with
      relevant illustrations. A review of the literature concerning the anatomy,
      procedure development, and outcomes is presented. The pelvic peritoneum was
      originally used in neovaginal construction for females with vaginal agenesis as a
      result of MRKH syndrome. The use of this technique to create a neovagina in male
      to-female transgender reassignment surgery has become appealing owing to the
      relative ease of the procedure, low complication rates, and overall high patient
      satisfaction. This technique offers a potential new choice for transgender male
      to-female neovaginal construction, but further studies are needed to confirm its
      successful use in transgender surgery. Clin. Anat. 31:175-180, 2018. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29178544
TI  - Measuring the quality of pressure ulcer prevention: A systematic mapping review
      of quality indicators.
AB  - The aim of this study was to provide a systematic overview of available pressure
      ulcer prevention quality indicators and to evaluate the underlying empirical
      evidence. A systematic mapping review was conducted with combined searches in
      Embase and Medline, and websites of relevant institutions and organisations. The
      eligibility criteria were clear use of the term "quality indicator" regarding
      pressure ulcer prevention; English or German language; and all settings,
      populations, and types of resources, including articles, brochures, and online
      material. In total, n = 146 quality indicators were identified. Most indicators
      were published in the United States (n = 50). The majority of indicators was
      developed for the hospital setting (n = 102). Process indicators were the most
      common (n = 71), followed by outcome indicators (n = 49). Less than half of
      identified indicators appeared to be practically used. Evidence supporting the
      validity and reliability were reported for n = 25 and n = 30 indicators
      respectively. The high number of indicators demonstrate the importance of
      measuring pressure ulcer prevention quality. This is not an indicator of our
      ability to accurately measure and evaluate this construct. There is an urgent
      need to develop evidence-based and internationally comparable indicators to help
      improve patient care and safety worldwide.

PMID- 29178546
TI  - Evaluation of dosimetric advantages of using patient-specific aperture system
      with intensity-modulated proton therapy for the shallow depth tumor.
AB  - In this study, we evaluate dosimetric advantages of using patient-specific
      aperture system with intensity-modulated proton therapy (IMPT) for head and neck
      tumors at the shallow depth. We used four types of patient-specific aperture
      system (PSAS) to irradiate shallow regions less than 4 g/cm2 with a sharp lateral
      penumbra. Ten head and neck IMPT plans with or without aperture were optimized
      separately with the same 95% prescription dose and same dose constraint for
      organs at risk (OARs). The plans were compared using dose volume histograms
      (DVHs), dose distributions, and some dose indexes such as volume receiving 50% of
      the prescribed dose (V50 ), mean or maximum dose (Dmean and Dmax ) to the OARs.
      All examples verified in this study had decreased V50 and OAR doses. Average,
      maximum, and minimum relative reductions of V50 were 15.4%, 38.9%, and 1.0%,
      respectively. Dmax and Dmean of OARs were decreased by 0.3% to 25.7% and by 1.0%
      to 46.3%, respectively. The plans with the aperture over more than half of the
      field showed decreased V50 or OAR dose by more than 10%. The dosimetric advantage
      of patient-specific apertures with IMPT was clarified in many cases. The PSAS has
      some dosimetric advantages for clinical use, and in some cases, it enables to
      fulfill dose constraints.

PMID- 29178547
TI  - Safe-by-Design Ligand-Coated ZnO Nanocrystals Engineered by an Organometallic
      Approach: Unique Physicochemical Properties and Low Toxicity toward Lung Cells.
AB  - The unique physicochemical properties and biocompatibility of zinc oxide
      nanocrystals (ZnO NCs) are strongly dependent on the nanocrystal/ligand
      interface, which is largely determined by synthetic procedures. Stable ZnO NCs
      coated with a densely packed shell of 2-(2-methoxyethoxy)acetate ligands, which
      act as miniPEG prototypes, with average core size and hydrodynamic diameter of 4
      5 and about 12 nm, respectively, were prepared by an organometallic self
      supporting approach, fully characterized, and used as a model system for
      biological studies. The ZnO NCs from the one-pot, self-supporting organometallic
      procedure exhibit unique physicochemical properties such as relatively high
      quantum yield (up to 28 %), ultralong photoluminescence decay (up to 2.1 MUs),
      and EPR silence under standard conditions. The cytotoxicity of the resulting ZnO
      NCs toward normal (MRC-5) and cancer (A549) human lung cell lines was tested by
      MTT assay, which demonstrated that these brightly luminescent, quantum-sized ZnO
      NCs have a low negative impact on mammalian cell lines. These results
      substantiate that the self-supporting organometallic approach is a highly
      promising method to obtain high-quality, nontoxic, ligand-coated ZnO NCs with
      prospective biomedical applications.

PMID- 29178545
TI  - Genome-Wide Study of Subcutaneous and Visceral Adipose Tissue Reveals Novel Sex
      Specific Adiposity Loci in Mexican Americans.
AB  - OBJECTIVE: This study aimed to explore the genetic mechanisms of regional fat
      deposition, which is a strong risk factor for metabolic diseases beyond total
      adiposity. METHODS: A genome-wide association study of 7,757,139 single
      nucleotide polymorphisms (SNPs) in 983 Mexican Americans (nmale  = 403; nfemale 
      = 580) from the Insulin Resistance Atherosclerosis Family Study was performed.
      Association analyses were performed with and without sex stratification for
      subcutaneous adipose tissue, visceral adipose tissue (VAT), and visceral
      subcutaneous ratio (VSR) obtained from computed tomography. RESULTS: The
      strongest signal identified was SNP rs2185405 (minor allele frequencies [MAF] =
      40%; PVAT  = 1.98 * 10-8 ) with VAT. It is an intronic variant of the GLIS family
      zinc finger 3 gene (GLIS3). In addition, SNP rs12657394 (MAF = 19%) was
      associated with VAT in males (Pmale  = 2.39*10-8 ; Pfemale  = 2.5 * 10-3 ). It is
      located intronically in the serum response factor binding protein 1 gene
      (SRFBP1). On average, male carriers of the variant had 24.6 cm2 increased VAT
      compared with noncarriers. Subsequently, genome-wide SNP-sex interaction analysis
      was performed. SNP rs10913233 (MAF = 14%; Pint  = 3.07 * 10-8 ) in PAPPA2 and
      rs10923724 (MAF = 38%; Pint  = 2.89 * 10-8 ) upstream of TBX15 were strongly
      associated with the interaction effect for VSR. CONCLUSIONS: Six loci were
      identified with genome-wide significant associations with fat deposition and
      interactive effects. These results provided genetic evidence for a differential
      basis of fat deposition between genders.

PMID- 29178548
TI  - Preservation of neuronal functions by exosomes derived from different human
      neural cell types under ischemic conditions.
AB  - Stem cell-based therapies have been reported in protecting cerebral infarction
      induced neuronal dysfunction and death. However, most studies used rat/mouse
      neuron as model cell when treated with stem cell or exosomes. Whether these
      findings can be translated from rodent to humans has been in doubt. Here, we used
      human embryonic stem cell-derived neurons to detect the protective potential of
      exosomes against ischemia. Neurons were treated with in vitro oxygen-glucose
      deprivation (OGD) for 1 h. For treatment group, different exosomes were derived
      from neuron, embryonic stem cell, neural progenitor cell and astrocyte
      differentiated from H9 human embryonic stem cell and added to culture medium 30
      min after OGD (100 MUg/mL). Western blotting was performed 12 h after OGD, while
      cell counting and electrophysiological recording were performed 48 h after OGD.
      We found that these exosomes attenuated OGD-induced neuronal death, Mammalian
      target of rapamycin (mTOR), pro-inflammatory and apoptotic signaling pathway
      changes, as well as basal spontaneous synaptic transmission inhibition in varying
      degrees. The results implicate the protective effect of exosomes on OGD-induced
      neuronal death and dysfunction in human embryonic stem cell-derived neurons,
      potentially through their modulation on mTOR, pro-inflammatory and apoptotic
      signaling pathways.

PMID- 29178550
TI  - Ultrathin 2D Photocatalysts: Electronic-Structure Tailoring, Hybridization, and
      Applications.
AB  - As a sustainable technology, semiconductor photocatalysis has attracted
      considerable interest in the past several decades owing to the potential to
      relieve or resolve energy and environmental-pollution issues. By virtue of their
      unique structural and electronic properties, emerging ultrathin 2D materials with
      appropriate band structure show enormous potential to achieve efficient
      photocatalytic performance. Here, the state-of-the-art progress on ultrathin 2D
      photocatalysts is reviewed and a critical appraisal of the classification,
      controllable synthesis, and formation mechanism of ultrathin 2D photocatalysts is
      presented. Then, different strategies to tailor the electronic structure of
      ultrathin 2D photocatalysts are summarized, including component tuning, thickness
      tuning, doping, and defect engineering. Hybridization with the introduction of a
      foreign component and maintaining the ultrathin 2D structure is presented to
      further boost the photocatalytic performance, such as quantum dots/2D materials,
      single atoms/2D materials, molecular/2D materials, and 2D-2D stacking materials.
      More importantly, the advancement of versatile photocatalytic applications of
      ultrathin 2D photocatalysts in the fields of water oxidation, hydrogen evolution,
      CO2 reduction, nitrogen fixation, organic syntheses, and removal pollutants is
      discussed. Finally, the future opportunities and challenges regarding ultrathin
      2D photocatalysts to bring about new opportunities for future research in the
      field of photocatalysis are also presented.

PMID- 29178549
TI  - Evaluation of AAPM Reports 204 and 220: Estimation of effective diameter, water
      equivalent diameter, and ellipticity ratios for chest, abdomen, pelvis, and head
      CT scans.
AB  - PURPOSE: To confirm AAPM Reports 204/220 and provide data for the future
      expansion of these reports by: (a) presenting the first large-scale confirmation
      of the reports using clinical data, (b) providing the community with size
      surrogate data for the head region which was not provided in the original
      reports, and additionally providing the measurements of patient ellipticity ratio
      for different body regions. METHOD: A total of 884 routine scans were included in
      our analysis including data from the head, thorax, abdomen, and pelvis for adults
      and pediatrics. We calculated the ellipticity ratio and all of the size
      surrogates presented in AAPM Reports 204/220. We correlated the purely geometric
      based metrics with the "gold standard" water-equivalent diameter (DW ). RESULTS:
      Our results and AAPM Reports 204/220 agree within our data's 95% confidence
      intervals. Outliers to the AAPM reports' methods were caused by excess gas in the
      GI tract, exceptionally low BMI, and cranial metaphyseal dysplasia. For the head,
      we show lower correlation (R2 = 0.812) between effective diameter and DW relative
      to other body regions. The ellipticity ratio of the shoulder region was the
      highest at 2.28 +/- 0.22 and the head the smallest at 0.85 +/- 0.08. The abdomen
      pelvis, chest, thorax, and abdomen regions all had ellipticity values near 1.5.
      CONCLUSION: We confirmed AAPM reports 204/220 using clinical data and identified
      patient conditions causing discrepancies. We presented new size surrogate data
      for the head region and for the first time presented ellipticity data for all
      regions. Future automatic exposure control characterization should include
      ellipticity information.

PMID- 29178551
TI  - Solubilization and Upgrading of High Polyethylene Terephthalate Loadings in a Low
      Costing Bifunctional Ionic Liquid.
AB  - The solubilization and efficient upgrading of high loadings of polyethylene
      terephthalate (PET) are important challenges, and most solvents for PET are
      highly toxic. Herein, a low-cost (ca. $1.2 kg-1 ) and biocompatible ionic liquid
      (IL), cholinium phosphate ([Ch]3 [PO4 ]), is demonstrated for the first time to
      play bifunctional roles in the solubilization and glycolytic degradation of PET.
      A high loading of PET (10 wt %) was readily dissolved in [Ch]3 [PO4 ] at
      relatively low temperatures (120  degrees C, 3 h) and under water-rich
      conditions. In-depth analysis of the solution revealed that high PET
      solubilization in [Ch]3 [PO4 ] could be ascribed to significant PET
      depolymerization. Acid precipitation yielded terephthalic acid as the dominant
      depolymerized monomer with a theoretical yield of approximately 95 %. Further
      exploration showed that in the presence of ethylene glycol (EG), the [Ch]3 [PO4 ]
      catalyzed glycolysis of PET could efficiently occur with approximately 100 %
      conversion of PET and approximately 60.6 % yield of bis(2
      hydroxyethyl)terephthalate under metal-free conditions. The IL could be reused at
      least three times without an apparent decrease in activity. NMR spectroscopy
      analysis revealed that strong hydrogen-bonding interactions between EG and the IL
      played an important role in the activation of EG and promotion of the glycolysis
      reaction. This study opens up avenues for exploring environmentally benign and
      efficient IL technology for solubilizing and recycling postconsumer polyester
      plastics.

PMID- 29178552
TI  - Educational and practice gaps in the management of volar melanocytic lesions.
AB  - BACKGROUND: The benign and malignant patterns of acral melanocytic naevi (AMN)
      and acral melanomas (AM) have been defined in a series of retrospective studies.
      A three-step algorithm was developed to determine when to biopsy acral
      melanocytic lesions. This algorithm has only been applied to a Japanese
      population. OBJECTIVES: Our study aimed to review the current management strategy
      of acral melanocytic lesions and to investigate the utility of the three-step
      algorithm in a predominately Caucasian cohort. METHODS: A retrospective search of
      the pathology and image databases at Mayo Clinic was performed between the years
      2006 and 2016. Only cases located on a volar surface with dermoscopic images were
      included. Two dermatologists reviewed all dermoscopic images and assigned a
      global dermoscopic pattern. Clinical and follow-up data were gathered by chart
      review. All lesions with known diameter and pathological diagnosis were used for
      the three-step algorithm. RESULTS: Regular fibrillar and ridge patterns were more
      likely to be biopsied (P = 0.01). The majority of AMN (58.1%) and AM (60%)
      biopsied were due to physician-deemed concerning dermoscopic patterns. 39.2% of
      these cases were parallel furrow, lattice-like or regular fibrillar. When
      patients were asked to follow-up within a 3- to 6-month period, only 16.7% of the
      patients returned within that interval. The three-step algorithm would have
      correctly identified four of five AM for biopsy, missing a 6 mm, multicomponent,
      invasive melanoma. CONCLUSION: We found one major educational gap in the
      recognition of low-risk lesions with high rates of biopsy of the fibrillary
      pattern. Recognizing low-risk dermoscopic patterns could reduce the rate of
      biopsy of AMN by 23.3%. We identified two major practice gaps, poor patient
      compliance with follow-up and the potential insensitivity of the three-step
      algorithm to small multicomponent acral melanocytic lesions.

PMID- 29178553
TI  - Advancing alcohol research and treatment: contentions and debates about treatment
      intensity, goals and outcomes in the 1970s and 1980s.
AB  - AIMS: This narrative exploration of alcohol treatment research focuses on key
      contentions and advances in alcohol treatment during the critical 1970s and
      1980s. METHODS: Papers and books which signal some of the major debates and
      advances in alcohol treatment research were selected from the 1970s and 1980s.
      The selection process was based on significant debate during this period, and
      included those that influenced the field in general and this author in
      particular. RESULTS: This was a period where challenges to traditional models and
      concepts, and the perceived universal need for long-term treatment, were
      accompanied by contention but also advances in research and treatment approaches.
      The debates and advances resonate today. These include the recognition that:
      intensive and long-term treatment is not always required; for dependent drinkers,
      relapse is a common treatment outcome meriting specific treatment approaches to
      prevent and reduce this risk; controlled drinking is a treatment option,
      especially for younger and less dependent drinkers; and an important contributor
      to enduring change is access to, and realization of, improvements in the quality
      of life. CONCLUSIONS: Pioneering research and publications in the 1970s and
      1980s, sometimes conducted and produced in contentious contexts, influenced
      significantly conceptualizations of alcohol-related problems, and laid the
      foundations for treatment hypotheses and research, improving access to a broader
      range of evidence-based treatment. These underpinning works influenced the
      development of stepped-up care from brief to intensive interventions, relapse
      prevention and treatment options not limited to abstinence, and they identified
      the need to include a stronger focus on quality of life.

PMID- 29178555
TI  - Ideal Dimers of Gold Nanospheres for Precision Plasmonics: Synthesis and
      Characterization at the Single-Particle Level for Identification of Higher Order
      Modes.
AB  - Ideal dimers comprising gold nanoparticles with a smooth surface and high
      sphericity are synthesized by a substrate-based assembly strategy with efficient
      cetyltrimethylammonium bromide removal. An unprecedented structural and plasmonic
      uniformity at the single-particle level is observed since inhomogeneities
      resulting from variations in gap morphology are eliminated. Single ideal dimers
      are analyzed by polarization-resolved dark-field scattering spectroscopy.
      Contributions from transverse as well as quadrupolar and octupolar longitudinal
      plasmon coupling modes can be discriminated because of their orthogonal
      polarization behavior. The assignment of these higher order coupling modes is
      supported by computer simulations.

PMID- 29178554
TI  - Selective T-cell depletion targeting CD45RA reduces viremia and enhances early T
      cell recovery compared with CD3-targeted T-cell depletion.
AB  - BACKGROUND: T-cell depletion (TCD) effectively reduces severe graft-versus-host
      disease in recipients of HLA-mismatched allografts. However, TCD is associated
      with delayed immune recovery and increased infections. We hypothesized that
      specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+
      T cells, can preserve memory-immunity in the allografts and confer protection
      against important viral infections in the early post-transplant period. METHODS:
      Sixty-seven patients who received TCD haploidentical donor transplantation for
      hematologic malignancy on 3 consecutive trials were analyzed. RESULTS: Patients
      receiving CD45RA-depleted donor grafts had 2000-fold more donor T cells infused,
      significantly higher T-cell counts at Day +30 post transplant (550/MUL vs 10/MUL;
      P < .001), and higher T-cell diversity by Vbeta spectratyping at Day +100 (P <
      .001). Importantly, these recipients experienced a significant reduction in both
      the incidence (P = .002) and duration (P = .02) of any viremia (cytomegalovirus,
      Epstein-Barr virus, or adenovirus) in the first 6 months post transplant.
      Specifically, recipients of CD3-depleted grafts were more likely to experience
      adenovirus viremia (27% vs 4%, P = .02). CONCLUSION: CD45RA-depletion provided a
      large number of donor memory T cells to the recipients and was associated with
      enhanced early T-cell recovery and protection against viremia.

PMID- 29178556
TI  - Prominent pulmonary venous flow mimicking mitral regurgitation.
AB  - The present case highlights a potential pitfall in assessing mitral regurgitation
      severity due to the presence of similar colored prominent pulmonary vein signals
      in the left atrium during color Doppler examination.

PMID- 29178557
TI  - Theta synchronization over occipito-temporal cortices during visual perception of
      body parts.
AB  - Categorical clustering in the visual system is thought to have evolved as a
      function of intrinsic (intra-areal) and extrinsic (interareal) connectivity and
      experience. In the visual system, the extrastriate body area (EBA), an occipito
      temporal region, responds to full body and body part images under the
      organizational principle of their functional/semantic meaning. Although frequency
      specific modulations of neural activity associated with perceptive and cognitive
      functions are increasingly attracting the interest of neurophysiologists and
      cognitive neuroscientists, perceiving single body parts with different functional
      meaning and full body images induces time-frequency modulations over occipito
      temporal electrodes are yet to be described. Here, we studied this issue by
      measuring EEG in participants who passively observed fingers, hands, arms and
      faceless full body images with four control plant stimuli, each bearing
      hierarchical analogy with the body stimuli. We confirmed that occipito-temporal
      electrodes (compatible with the location of EBA) show a larger event-related
      potential (ERP, N190) for body-related images. Furthermore, we identified a body
      part-specific (i.e. selective for hands and arms) theta event-related
      synchronization increase under the same electrodes. This frequency modulation
      associated with the perception of body effectors over occipito-temporal cortices
      is in line with recent findings of categorical organization of neural responses
      to human effectors in the visual system.

PMID- 29178558
TI  - Effectiveness of different numbers of simulation training models on medical
      students' cervical examination performance.
AB  - OBJECTIVE: To estimate whether different numbers of simulation training models
      affect medical students' cervical examination performance. METHODS: In a
      prospective study at Peking Union Medical College Hospital, Beijing, China,
      between August 1, 2016, and April 30, 2017, fifth-year medical students without
      obstetric experience were randomly assigned to the large or small number training
      groups. Participants in the large number group performed cervical examinations on
      10 dilation models and nine effacement/consistency models; those in the small
      number group practiced on four dilation models and three effacement/consistency
      models. In the examination, both groups evaluated 10 models in the same sequence
      and reported findings. Participants also completed confidence surveys. Mann
      Whitney U test was used to compare the assessment accuracy and confidence
      improvement between the groups. RESULTS: There were 91 students randomized to the
      large (n=45) or small (n=46) number training groups. As compared with the small
      number group, the large number group demonstrated higher accuracy in assessing
      exact dilation (P=0.028), exact effacement (P=0.002), effacement within 0.5 cm
      (P=0.017), and consistency (P=0.045). There was no difference in assessing
      dilation within 1 cm or in confidence improvement between the groups. CONCLUSION:
      A small number of simulation training models was sufficient to improve students'
      accuracy and confidence in assessing cervical dilatation, although a large number
      was needed to improve accuracy in cervical effacement and consistency.

PMID- 29178560
TI  - Nomenclature for factors of the HLA system, update August 2017.

PMID- 29178559
TI  - ARID1A, a component of SWI/SNF chromatin remodeling complexes, is required for
      porcine embryo development.
AB  - Mammalian embryos undergo dramatic epigenetic remodeling that can have a profound
      impact on both gene transcription and overall embryo developmental competence.
      Members of the SWI/SNF (Switch/Sucrose non-fermentable) family of chromatin
      remodeling complexes reposition nucleosomes and alter transcription factor
      accessibility. These large, multi-protein complexes possess an SNF2-type ATPase
      (either SMARCA4 or SMARCA2) as their core catalytic subunit, and are directed to
      specific loci by associated subunits. Little is known about the identity of
      specific SWI/SNF complexes that serve regulatory roles during cleavage
      development. ARID1A, one of the SWI/SNF complex subunits, can affect histone
      methylation in somatic cells; here, we determined the developmental requirements
      of ARID1A in porcine oocytes and embryos. We found ARID1A transcript levels were
      significantly reduced in 4-cell porcine embryos as compared to germinal vesicle
      stage oocytes, suggesting that ARID1A would be required for porcine cleavage
      stage development. Indeed, injecting in vitro-matured and fertilized porcine
      oocytes with double-stranded interfering RNAs that target ARID1A, and evaluating
      their phenotype after seven days, revealed that the depletion of ARID1A results
      in significantly fewer cells than their respective control groups (p < 0.001).

PMID- 29178561
TI  - Excited-State Dipole Moments and Transition Dipole Orientations of Rotamers of
      1,2-, 1,3-, and 1,4-Dimethoxybenzene.
AB  - Rotationally resolved electronic Stark spectra of rotamers of 1,2-, 1,3-, and 1,4
      dimethoxybenzene have been recorded and analyzed using evolutionary strategies.
      The experimentally determined dipole moments as well as the transition dipole
      moments are compared to the results of ab initio calculations. For the electronic
      ground states of the experimentally observed dimethoxybenzenes, the permanent
      dipole moments can be obtained from vectorial addition of the monomethoxybenzene
      dipole moment. However, this is not the case for the electronically excited
      states. This behavior can be traced back to a state mixing of the lowest
      electronically excited singlet states for the asymmetric rotamers. For the
      symmetric rotamers however, this is not valid. We discuss several possible
      reasons for the non-additivity of the dipole moments in the excited states of the
      symmetric rotamers.

PMID- 29178562
TI  - Macrolide use in the previous years is associated with failure to eradicate
      Helicobacter pylori with clarithromycin-containing regimens.
AB  - BACKGROUND: There is some evidence that prior use of macrolide antibiotics is a
      useful predictor of the likelihood of standard triple therapy failure in
      Helicobacter pylori eradication. In this study, we have evaluated whether
      previous intake of macrolides correlates with failure to eradicate H. pylori
      using two different first-line clarithromycin-containing regimens. MATERIALS AND
      METHODS: Retrospective study of 212 patients with H. pylori infection treated
      with one of two first-line clarithromycin-containing regimens: 108 patients
      treated with triple therapy for 10 days and 104 patients treated with concomitant
      therapy for 10 days. The intake of macrolides (clarithromycin, azithromycin, and
      other macrolides) prior to the eradication therapy was obtained from the
      electronic medical record, which contains information regarding all the
      medication prescribed to the patients since the year 2004. RESULTS: One hundred
      of 212 patients (47.2%) had received at least one treatment with macrolides
      during the years prior to the eradication therapy. H. pylori eradication rates
      were significantly lower in patients with previous use compared to patients
      without previous use of macrolides, both with triple therapy (60.8% vs 92.9%; P <
      .0001) and with concomitant therapy (85.7% vs 98.2%; P = .024). CONCLUSIONS:
      Previous use of macrolides correlates with a low H. pylori eradication rate with
      triple and concomitant clarithromycin-containing regimens. In addition, our study
      shows that in patients without previous use of macrolides, triple therapy
      achieves per-protocol eradication rates over 90%.

PMID- 29178564
TI  - A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft
      Rejection.
AB  - Acute allograft rejection remains common after liver transplantation despite
      modern immunosuppressive agents. In addition, the long-term side effects of these
      regimens, including opportunistic infections, are challenging. This study
      evaluated the safety and clinical feasibility of umbilical cord-derived
      mesenchymal stem cell (UC-MSC) therapy in liver transplant patients with acute
      graft rejection. Twenty-seven liver allograft recipients with acute rejection
      were randomly assigned into the UC-MSC infusion group or the control group.
      Thirteen patients received one infusion of UC-MSCs (1 * 106 /kg body weight); one
      patient received multiple UC-MSC infusions; 13 patients were used as controls.
      All enrolled patients received conventional immunosuppressive agents with follow
      up for 12 weeks after UC-MSC infusions. No side effects occurred in treated
      patients. Four weeks after UC-MSC infusions, alanine aminotransferase levels had
      decreased markedly and remained lower throughout the 12-week follow-up period.
      Importantly, allograft histology was improved after administration of UC-MSCs.
      The percentage of regulatory T cells (Tregs) and the Treg/T helper 17 (Th17) cell
      ratio were significantly increased 4 weeks after infusions; in contrast, the
      percentage of Th17 cells showed a decreasing trend. In controls, the percentages
      of Tregs and Th17 cells and the Treg/Th17 ratio were statistically unchanged from
      the baseline measurements. Transforming growth factor beta 1 and prostaglandin E2
      were increased significantly after UC-MSC infusions; by contrast, there were no
      significant changes in controls. Our data suggest that UC-MSC infusion for acute
      graft rejection following liver transplantation is feasible and may mediate a
      therapeutic immunosuppressive effect. Stem Cells Translational Medicine
      2017;6:2053-2061.

PMID- 29178565
TI  - Adults with intellectual disabilities in China: comorbid psychiatric disorder and
      its association with health service utilisation.
AB  - BACKGROUND: Adults with intellectual disabilities (ID) often have multiple
      comorbidities. Psychiatric disorders in this population have been poorly studied
      in developing countries. We aimed to investigate the prevalence of psychiatric
      disorders in adults with ID and whether comorbid psychiatric disorders were
      associated with health service utilisation. METHODS: We obtained data from the
      Second National Sample Survey on Disability, conducted in 31 provinces of China
      and selected a subsample of 13 631 adults aged 18 years and above with ID. ID
      were defined by intelligence quotient score under 70, deficits in two or more
      adaptive behaviours and age of onset under 18 years. Psychiatric disorders were
      identified according to the International Statistical Classification of Diseases,
      Tenth Revision. Logistic regressions were used for data analyses. RESULTS: The
      prevalence of psychiatric disorders in adults with ID was 16.7%. The most
      prevalent type of psychiatric disorder was dementia. Older adults, females, being
      minorities, urban residents, being literate, low-income groups and having severe
      ID, were associated with elevated risk of psychiatric disorder among adults with
      ID. Compared with individuals without psychiatric disorders, those with comorbid
      psychiatric disorders were more likely to use medical service and less likely to
      use rehabilitation service. CONCLUSIONS: The prevalence of psychiatric disorder
      in adults with ID was strikingly higher than that in the general population.
      Health service utilisation among Chinese adults with ID remained a big challenge.
      There is a possibility of diagnostic overshadowing by local clinicians, which may
      have resulted in overdiagnosis of dementia and underdiagnosis of common mental
      disorders. This study informs further investigations regarding common mental
      disorders among people with ID and has implications for public health strategies
      and health policies to meet health service need for this population.

PMID- 29178566
TI  - Bridging the gap for future clinician-educators.
AB  - BACKGROUND: In contrast to the training required in the UK, opportunities for
      medical education training in the USA are limited. Resident-as-teacher programmes
      are typically insufficient to prepare trainees to be successful clinician
      educators, but few pursue formal education degrees. We sought to assess the need
      for, and feasibility of, a training pathway for subspecialty fellows in a large
      Department of Medicine that would prepare our trainees to become effective
      educators. METHODS: Quantitative and qualitative methods were used. Previous
      fellowship applicants and current programme directors were surveyed to determine
      the potential benefits of the programme. A pilot programme was conducted with
      fellows interested in education to determine the feasibility of the programme.
      Pilot participants were interviewed regarding the benefits that they gained from
      the pilot and the logistical challenges that they experienced. In contrast to the
      training required in the UK, opportunities for medical education training in the
      USA are limited RESULTS: Five highly ranked fellows would have scored our
      programmes higher if we offered this training pathway. Pilot participants and
      fellowship programme directors agreed that there is a compelling need for such a
      training pathway. A number of themes arose from the interviews that enabled us to
      build the framework for a strong programme. DISCUSSION: Our findings suggest that
      a clinician-educator training pathway that draws from multiple subspecialties has
      the potential to improve recruitment, provide needed career counselling and
      skills development to trainees, and to build a community of educators that will
      benefit the institution. Important insights from pilot participant interviews
      will inform the programme design, in order to keep trainees engaged and overcome
      logistical challenges.

PMID- 29178567
TI  - Prognostic markers in congenital diaphragmatic hernia: Left ventricular diameter
      and pulmonary hypertension.
AB  - BACKGROUND: The aim of this study was to investigate whether the outcome of
      congenital diaphragmatic hernia (CDH) in newborns can be predicted using left
      ventricular (LV) diameter and estimated pulmonary artery pressure. METHODS:
      Patients in the newborn unit in 2012-2016 were screened retrospectively.
      Echocardiographic measurements of 35 patients with isolated left lateral CDH and
      27 healthy newborns were compared in the first 24 h of life. RESULTS: Mean LV end
      diastolic diameter (LVEDD) and end-systolic diameter (LVESD), and LV ejection
      fraction were significantly lower in the CDH group. Moreover, tricuspid
      regurgitation (TR) and pulmonary regurgitation (PR) were significantly higher
      than in the controls (P < 0.001). Six CDH patients died within the next 40 days
      after birth. Mean LVEDD and LVESD were significantly lower in the CHD patients
      who died compared with those who were discharged (P < 0.001, P = 0.016). Also,
      mean TR and PR (P < 0.001) and the frequency of pulmonary hypertension (PH; P =
      0.001) were significantly higher in these patients. On receiver operating
      characteristic analysis of the CDH non-survivors, LVEDD < 11 mm (sensitivity,
      100%; 95%CI: 87.9-100; specificity, 100%; 95%CI: 54.1-100) and TR > 3.5 m/s
      (sensitivity, 89.66%; 95%CI: 72.6-97.7; specificity, 100%; 95%CI: 54.1-100) were
      associated with poor prognosis. CONCLUSIONS: Decrease in LVEDD and presence of PH
      are associated with poor prognosis. Also, PH was associated with mortality in CDH
      patients. Thus, outcome may be predicted on careful echocardiographic evaluation
      of the LV diameters and pulmonary pressure.

PMID- 29178568
TI  - Hypoxia-induced intestinal barrier changes in balloon-assisted enteroscopy.
AB  - KEY POINTS: Balloon-assisted enteroscopy (BAE) is an emerging standard procedure
      by utilizing distensible balloons to facilitate deep endoscopy in the small and
      large intestine. Sporadic cases of bacteraemia were found after BAE. Balloon
      distension by BAE caused gut tissue hypoxia. The impact of balloon distension
      induced hypoxia on intestinal barriers remains unclear. Murine models of BAE by
      colonic balloon distension showed that short- and long-term hypoxia evoked
      opposite effects on epithelial tight junctions (TJs). Short-term hypoxia
      fortified TJ integrity, whereas long-term hypoxia caused damage to barrier
      function. Our data showed for the first time the molecular mechanisms and
      signalling pathways of epithelial barrier fortification and TJ reorganization by
      short-term hypoxia for the maintenance of gut homeostasis. The findings suggest
      avoiding prolonged balloon distension during BAE to reduce the risk of hypoxia
      induced gut barrier dysfunction. ABSTRACT: Balloon-assisted enteroscopy (BAE) is
      an emerging standard procedure that uses distensible balloons to facilitate deep
      endoscopy. Intestines are known to harbour an abundant microflora. Whether
      balloon distension causes perturbation of blood flow and gut barrier dysfunction,
      and elicits risk of bacterial translocation remains unknown. Our aims were to (1)
      conduct a prospective study to gather microbiological and molecular evidence of
      bacterial translocation by BAE in patients, (2) establish a murine model of
      colonic balloon distension to investigate tissue hypoxia and intestinal barrier,
      and (3) assess the effect of short- and long-term hypoxia on epithelial
      permeability using cell lines. Thirteen patients were enrolled for BAE
      procedures, and blood samples were obtained before and after BAE for paired
      comparison. Four of the 13 patients (30.8%) had positive bacterial DNA in blood
      after BAE. Post-BAE endotoxaemia was higher than the pre-BAE level. Nevertheless,
      no clinical symptom of sepsis or fever was reported. To mimic clinical BAE, mice
      were subjected to colonic balloon distension. Local tissue hypoxia was observed
      during balloon inflation, and reoxygenation after deflation. A trend of increased
      gut permeability was seen after long-term distension, whereas a significant
      reduction of permeability was observed by short-term distension in the proximal
      colon. Human colonic epithelial Caco-2 cells exposed to hypoxia for 5-20 min
      exhibited increased tight junctional assembly, while those exposed to longer
      hypoxia displayed barrier disruption. In conclusion, sporadic cases of
      bacteraemia were found after BAE, without septic symptoms. Short-term hypoxia by
      balloon distension yielded a protective effect whereas long-term hypoxia caused
      damage to the gut barrier.

PMID- 29178570
TI  - Shared additive genetic variation for alcohol dependence among subjects of
      African and European ancestry.
AB  - Alcohol dependence (AD) affects individuals from all racial/ethnic groups, and
      previous research suggests that there is considerable variation in AD risk
      between and among various ancestrally defined groups in the United States.
      Although the reasons for these differences are likely due in part to
      contributions of complex sociocultural factors, limited research has attempted to
      examine whether similar genetic variation plays a role across ancestral groups.
      Using a pooled sample of individuals of African and European ancestry (AA/EA)
      obtained through data shared within the Database for Genotypes and Phenotypes, we
      estimated the extent to which additive genetic similarity for AD between AA and
      EAs using common single nucleotide polymorphisms overlapped across the two
      populations. AD was represented as a factor score by using Diagnostic and
      Statistical Manual dependence criteria, and genetic data were imputed by using
      the 1000 Genomes Reference Panel. Analyses revealed a significant single
      nucleotide polymorphism-based heritability of 17 percent (SE = 5) in EAs and 24
      percent (SE = 15) in AAs. Further, a significant genetic correlation of 0.77 (SE
      = 0.46) suggests that the allelic architecture influencing the AD factor for EAs
      and AAs is largely similar across the two populations. Analyses indicated that
      investigating the genetic underpinnings of alcohol dependence in different ethnic
      groups may serve to highlight core etiological factors common to both groups and
      unique etiological factors specific to each ethnic group.

PMID- 29178571
TI  - Rapidly enlarging breast mass in the setting of silicone injection augmentation
      mammoplasty.

PMID- 29178569
TI  - A Prospective Study of Obesity, Metabolic Health, and Cancer Mortality.
AB  - OBJECTIVE: This study examined whether metabolic health status is associated with
      risk of cancer mortality and whether this varies by body mass index (BMI)
      category. METHODS: A prospective study of 22,514 participants from the Reasons
      for Geographic and Racial Differences in Stroke (REGARDS) cohort was performed.
      Metabolically unhealthy status was defined as having three or more of the
      following: (1) elevated fasting glucose, (2) high triglycerides, (3)
      dyslipidemia, (4) hypertension, and (5) elevated waist circumference.
      Participants were categorized into normal weight (BMI 18.5-24.9 kg/m2 ),
      overweight (BMI 25.0-29.9 kg/m2 ), and obesity (BMI >= 30 kg/m2 ) groups. Cox
      proportional hazards regression was performed to estimate hazards ratios (HRs)
      and 95% confidence intervals (CIs) for cancer mortality during follow-up.
      RESULTS: Among participants with normal weight, participants who were
      metabolically unhealthy had an increased risk of cancer mortality (HR: 1.65; 95%
      CI: 1.20-2.26) compared with metabolically healthy participants. The overall
      mortality risk for participants who were metabolically unhealthy and had normal
      weight was stronger for obesity-related cancers (HR: 2.40; 95% CI: 1.17-4.91).
      Compared with participants with normal weight, those who were metabolically
      healthy and overweight were at a reduced risk of any cancer mortality (adjusted
      HR: 0.79; 95% CI: 0.63-0.99). CONCLUSIONS: There was an increased risk of overall
      and obesity-related cancer mortality among metabolically unhealthy participants
      with normal weight.

PMID- 29178572
TI  - Psychometric evaluation of the Arabic language person-centred climate
      questionnaire-staff version.
AB  - AIM: To evaluate the psychometric properties of the Arabic language person
      centred climate questionnaire-staff version. BACKGROUND: There have been
      increasing calls for a person-centred rather than a disease-centred approach to
      health care. A limited number of tools measure the extent to which care is
      delivered in a person-centred manner, and none of these tools have been validated
      for us in Arab settings. METHOD: The validated form of the person-centred climate
      questionnaire-staff version was translated into Arabic and distributed to 152
      health care staff in teaching and non-teaching hospitals in Saudi Arabia.
      Statistical estimates of validity and reliability were used for psychometric
      evaluation. RESULTS: Items on the Arabic form of the person-centred climate
      questionnaire-staff version had high reliability (Cronbach's alpha .98).
      Cronbach's alpha values for the three sub-scales (safety, everydayness and
      community), were .96, .97 and .95 respectively. Internal consistency was also
      high and measures of validity were very good. CONCLUSION: Arabic form of the
      person-centred climate questionnaire-staff version provides a valid and reliable
      way to measure the degree of perceived person-centredness. IMPLICATIONS FOR
      NURSING MANAGEMENT: The tool can be used for comparing levels of person
      centredness between wards, units, and public and private hospitals. The tool can
      also be used to measure the extent of person-centredness in health care settings
      in other Arab countries.

PMID- 29178573
TI  - Macrophages-common culprit in obesity and asthma.
AB  - Macrophages are essential innate immune cells that also regulate local
      metabolism. Endogenous or exogenous stimuli may polarize macrophages toward
      phenotypes that serve distinct innate immunological metabolic functions. IFN
      gamma or lipopolysaccharide (LPS) polarizes macrophages toward the M1, or
      "classically activated" phenotype that participates in defense against
      intracellular pathogens. IL-4, IL-13, or chitin polarizes macrophages toward the
      M2, or "alternatively activated" phenotype, which defends against multicellular
      nematodes and fungi. As macrophages polarize in local environments, M1 and M2
      macrophages may coexist in different organs and may differentially affect asthma
      and obesity, two comorbid diseases where polarized macrophages contribute to
      their pathogenesis. While M1 macrophages are considered beneficial in asthma and
      contribute to the pathology of obesity, M2 macrophages contribute to the
      pathology of asthma, but limit metabolic syndrome associated with obesity. Here,
      we discuss the roles for M1 and M2 macrophages in asthma and obesity, and propose
      a model by which M1-mediated inflammation in adipose tissue enhances M2-mediated
      inflammation in the asthmatic lung.

PMID- 29178574
TI  - Evidence for Triplet Sensitization in the Visible-Light-Induced [2+2]
      Photocycloaddition of Eniminium Ions.
AB  - Epsilonniminium ions were prepared from the corresponding alpha,beta-unsaturated
      carbonyl compounds (enones and enals), and were found to be promoted to their
      respective triplet states by energy transfer. The photoexcited intermediates
      underwent intra- or intermolecular [2+2] photocycloaddition in good yields (50-78
      %) upon irradiation at lambda=433 nm or lambda=457 nm. Iridium or ruthenium
      complexes with a sufficiently high triplet energy were identified as efficient
      catalysts (2.5 mol % catalyst loading) for the reaction. The intermolecular [2+2]
      photocycloaddition of an eniminium ion derived from a chiral secondary amine
      proceeded with high enantioselectivity (88 % ee).

PMID- 29178575
TI  - Serum IgA/C3 and glomerular C3 staining predict severity of IgA nephropathy.
AB  - BACKGROUND: The aim of this study was to determine whether serum immunoglobulin
      A/complement factor 3 (IgA/C3) ratio and glomerular C3 staining predict outcome
      in IgA nephropathy. METHODS: We collected data for 44 IgA nephropathy children
      treated with multi-drug combination therapy. The children were retrospectively
      divided into four groups based on serum IgA/C3 ratio and glomerular C3 staining:
      group A, IgA/C3 ratio >2.68 (median) and glomerular C3 staining >=2.0, n = 9;
      group B, IgA/C3 ratio >2.68 and glomerular C3 staining <2.0, n = 7; group C,
      IgA/C3 ratio <2.68 and glomerular C3 staining >=2.0, n = 7; and group D, IgA/C3
      ratio <2.68 and glomerular C3 staining <2.0, n = 21. Clinical features; pathology
      at the first and second renal biopsy and at the latest follow up; and prognosis
      were analyzed for the four groups. RESULTS: At the most recent follow up, urinary
      protein excretion, incidence of hematuria, and serum creatinine in group A were
      all higher than in group D. At the second biopsy, crescent absence/presence
      ratio; mesangial hypercellularity, segmental glomerulosclerosis or adhesion,
      endocapillary hypercellularity, and tubular atrophy/interstitial fibrosis as well
      as crescents and global glomerulosclerosis (MESTCG) score; and clonicity index in
      group A were higher than in group D. All patients in group D had normal urine,
      and the prevalence of persistent nephropathy in group A was higher than in group
      D. CONCLUSIONS: Serum IgA/C3 ratio and glomerular C3 staining can predict outcome
      in IgA nephropathy.

PMID- 29178576
TI  - The misunderstood TIGER.

PMID- 29178577
TI  - Dispersive magnetic solid-phase extraction of phthalate esters from water samples
      and human plasma based on a nanosorbent composed of MIL-101(Cr) metal-organic
      framework and magnetite nanoparticles before their determination by GC-MS.
AB  - In this study, a magnetic metal-organic framework was synthesized simply and
      utilized in the dispersive magnetic solid-phase extraction of five phthalate
      esters followed by their determination by gas chromatography with mass
      spectrometry. First, MIL-101(Cr) was prepared hydrothermally in water medium
      without using highly corrosive hydrofluoric acid, utilizing an autoclave oven
      heat supply. Afterward, Fe3 O4 nanoparticles were decorated into the matrix of
      MIL-101(Cr) to fabricate magnetic MIL-101 nanocomposite. The nanocomposite was
      characterized by various techniques. The parameters affecting dispersive magnetic
      solid-phase extraction efficiency were optimized and obtained as: a sorbent
      amount of 15 mg; a sorption time of 20 min; an elution time of 5 min; NaCl
      concentration, 10% w/v; type and volume of the eluent 1 mL n-hexane/acetone (1:1
      v/v). Under the optimum conditions detection limits and linear dynamic ranges
      were achieved in the range of 0.08-0.15 and 0.5-200 MUg/L, respectively. The
      intra- and interday RSD% values were obtained in the range of 2.5-9.5 and 4.6
      10.4, respectively. Ultimately, the applicability of the method was successfully
      confirmed by the extraction and determination of the model analytes in water
      samples, and human plasma in the range of microgram per liter and satisfactory
      results were obtained.

PMID- 29178578
TI  - Trends in maternal deaths in HIV-infected women, on a background of changing HIV
      management guidelines in South Africa: 1997 to 2015.
AB  - INTRODUCTION: As work begins towards the Sustainable Development Goal target of
      reducing the global maternal mortality ratio (MMR) to less than 70 deaths per
      100,000 live births by 2030, much needs to be done in ending preventable maternal
      deaths. After 1990, South Africa experienced a reversal of gains in decreasing
      maternal mortality, with an increase in HIV-related maternal deaths. In this
      study, we assessed trends in maternal mortality in HIV-infected women, on a
      background of an evolving HIV care programme. METHODS: This was a cross
      sectional, retrospective record review of maternal deaths in the obstetrics unit
      at Chris Hani Baragwanath Academic Hospital, in Johannesburg, South Africa, a
      referral hospital in a high HIV prevalence setting where the prevalence among
      pregnant women has plateaued around 29.0% for the past decade. Trends in HIV
      diagnosis and management in pregnancy, and causes of maternal deaths in HIV
      infected women were analysed over different time periods (1997 to 2003, 2004 to
      2009, 2010 to 2012, and 2013 to 2015) reflecting major guideline changes.
      RESULTS: From January 1997 to December 2015, there were 692 maternal deaths in
      the obstetrics unit. Of the 490 (70.8%) maternal deaths with a documented HIV
      status, 335 (68.4%) were HIV-infected. A Chi-squared test for trends showed that
      the institutional MMR (iMMR) in women known to be HIV-infected peaked in the
      period 2004 to 2009 at 380 (95% CI 319 to 446) per 100,000 live births, with a
      decline to 267 (95% CI 198 to 353) in 2013 to 2015, p = 0.049. This decrease
      coincided with changes in the South African HIV management guidelines, mainly
      increased availability of antiretroviral therapy (ART). Non-pregnancy related
      infections were the leading cause of death throughout the review period,
      accounting for 61.5% (206/335) of deaths. Only 23.3% (78/335) of the women who
      died were on ART at the time of death, this in the context of advanced immune
      suppression and an overall median CD4 count of 136 cells/MUl (interquartile
      ranges (IQR) 45 to 301). CONCLUSION: In this 19-year review of maternal deaths in
      Johannesburg, South Africa, there was evidence of a decrease in the iMMR among
      HIV-infected women, but it remains unacceptably high. Efforts to address drivers
      of mortality and barriers to accessing ART need to be accelerated if we are to
      see substantial decreases in maternal mortality.

PMID- 29178579
TI  - Vitamin D receptor expression in canine mammary gland and relationship with
      clinicopathological parameters and progesterone/oestrogen receptors.
AB  - The vitamin D receptor (VDR) belongs to the nuclear class II receptor family. VDR
      is a ligand transcription factor and mediates the actions of calcitriol, the
      active product of vitamin D synthesis. Nowadays, it is known that the biological
      actions of calcitriol include the capacity to modulate cancer features, such as
      proliferation and differentiation, apoptosis, angiogenesis, invasion and
      metastasis. VDR expression has been demonstrated in human breast cancer and
      vitamin D has emerged as a promising targeted therapy. We analyse the VDR
      expression in normal and neoplastic canine mammary tissue samples and its
      relationship with clinicopathological parameters and progesterone/oestrogens
      receptors (PR/ER). Expression of VDR, Ki67 (to evaluate the proliferation index,
      PI), PR and ER was assessed in 50 mammary gland tissue samples from 41 female
      dogs by immunohistochemistry. VDR-positive staining was found in the nuclei of
      both myoepithelial and luminal epithelial cell layers. VDR expression was higher
      in normal mammary tissue (37/37 cases, 100%) then followed by benign tumours
      (6/15 cases, 40%) and malignant tumours (9/34 cases, 26.5%) (P = .001). Female
      dogs aged >=10 years had lower VDR expression compared with dogs younger (P =
      .017). Relationship between VDR and breed, number of tumours, tumour size,
      histologic subtype, histologic grade of malignancy, PI and PR and ER expression
      was not observed. Studies with more samples are necessary to further evaluate the
      possible role of VDR in the biological behaviour of canine mammary tumours, and
      to corroborate the possibility to use the dog as model for human breast cancer.

PMID- 29178581
TI  - The Irrelevance of Getting Stronger or Weaker with Age.

PMID- 29178580
TI  - A cell-free platform for rapid synthesis and testing of active
      oligosaccharyltransferases.
AB  - Protein glycosylation, or the attachment of sugar moieties (glycans) to proteins,
      is important for protein stability, activity, and immunogenicity. However,
      understanding the roles and regulations of site-specific glycosylation events
      remains a significant challenge due to several technological limitations. These
      limitations include a lack of available tools for biochemical characterization of
      enzymes involved in glycosylation. A particular challenge is the synthesis of
      oligosaccharyltransferases (OSTs), which catalyze the attachment of glycans to
      specific amino acid residues in target proteins. The difficulty arises from the
      fact that canonical OSTs are large (>70 kDa) and possess multiple transmembrane
      helices, making them difficult to overexpress in living cells. Here, we address
      this challenge by establishing a bacterial cell-free protein synthesis platform
      that enables rapid production of a variety of OSTs in their active conformations.
      Specifically, by using lipid nanodiscs as cellular membrane mimics, we obtained
      yields of up to 420 MUg/ml for the single-subunit OST enzyme, "Protein
      glycosylation B" (PglB) from Campylobacter jejuni, as well as for three
      additional PglB homologs from Campylobacter coli, Campylobacter lari, and
      Desulfovibrio gigas. Importantly, all of these enzymes catalyzed N-glycosylation
      reactions in vitro with no purification or processing needed. Furthermore, we
      demonstrate the ability of cell-free synthesized OSTs to glycosylate multiple
      target proteins with varying N-glycosylation acceptor sequons. We anticipate that
      this broadly applicable production method will advance glycoengineering efforts
      by enabling preparative expression of membrane-embedded OSTs from all kingdoms of
      life.

PMID- 29178582
TI  - Erratum: The Dietary Intervention to Enhance Tracking with Mobile Devices (DIET
      Mobile) Study: A 6-Month Randomized Weight Loss Trial.

PMID- 29178583
TI  - Bariatric Surgery and the Incidence of Psoriasis and Psoriatic Arthritis in the
      Swedish Obese Subjects Study.
AB  - OBJECTIVE: The aim of this study was to assess the effect of bariatric surgery
      (vertical gastroplasty, gastric banding, or gastric bypass) compared with usual
      care on the incidence of psoriasis and psoriatic arthritis (PsA) in the Swedish
      Obese Subjects study. METHODS: This report includes 1,991 subjects who underwent
      bariatric surgery and 2,018 controls with obesity from the SOS study; none of
      them had psoriasis or PsA at baseline. Information about psoriasis and PsA
      diagnosis was retrieved through the Swedish National Patient Register and
      questionnaires. RESULTS: During follow-up for up to 26 years, bariatric surgery
      was associated with a lower incidence of psoriasis compared with usual care
      (number of events = 174; hazard ratio 0.65; 95% CI: 0.47-0.89; P = 0.008). Both
      smoking and a longer duration of obesity were independently associated with a
      higher risk for psoriasis. No significant difference was detected among the three
      surgical procedures in terms of lowering the risk of developing psoriasis. The
      association between bariatric surgery and psoriasis incidence was not influenced
      by baseline confounders. No significant difference in the risk of developing PsA
      (number of events = 46) was detected when comparing the surgery and the control
      groups. CONCLUSIONS: This study shows that bariatric surgery is associated with a
      lower risk of developing psoriasis compared with usual care.

PMID- 29178584
TI  - Age Variation in the Association Between Obesity and Mortality in Adults.
AB  - OBJECTIVE: The aim of this study was to evaluate the previously reported finding
      that the association between obesity and mortality strengthens with increasing
      age. METHODS: The data were derived from the National Health Interview Survey.
      Age-specific hazard ratios of mortality for grade 2/3 obesity (BMI >= 35 kg/m2 ),
      relative to a BMI of 18.5 kg/m2 to < 25 kg/m2 , were calculated by using a
      flexible parametric survival model (240,184 white men) and Cox proportional
      hazard models (51,697 matched pairs). RESULTS: When the model included
      interaction terms between obesity and age at the survey, hazard ratios appeared
      to increase with age if those interaction terms were ignored by fixing age at the
      survey as a single value. However, when recalculated for adults with various ages
      at the survey, according to model specifications, hazard ratios were higher for
      younger adults than for older adults with the same follow-up duration. Based on
      matched data, hazard ratios were also higher for younger adults (2.14 [95% CI:
      1.90-2.40] for those 40-49 years of age) than for older adults (1.22 [95%: 0.91
      1.63] for those 90+ years of age). CONCLUSIONS: For any given follow-up duration,
      the association between obesity and mortality weakens with age. The previously
      reported strengthening of the obesity-mortality association with increasing age
      was caused by the failure to take all the model specifications into consideration
      when calculating adjusted hazard ratios.

PMID- 29178586
TI  - Lessons To Be Learned: The Molecular Basis of Kinase-Targeted Therapies and Drug
      Resistance in Non-Small Cell Lung Cancer.
AB  - The treatment of non-small cell lung cancer (NSCLC) is currently experiencing a
      revolution. Over the last decade, the knowledge gained about the biochemical
      features of biomarkers and their predictive abilities has led to the development
      of targeted small-molecule inhibitors that present an alternative to harsh
      chemotherapy. The use of these new therapies has improved the quality of life and
      increased the survival of patients. The occurrence of inevitable drug resistance
      requires the constant development of precision medicine. The detailed
      understanding of the target biology and the search for innovative chemical
      approaches has encouraged investigations in this field. Herein, we review
      selected aspects of the molecular targets and present an overview of current
      topics and challenges in the rational development of small molecules to target
      NSCLC.

PMID- 29178585
TI  - Volumetric-modulated arc therapy versus intensity-modulated radiotherapy for
      large volume retroperitoneal sarcomas: A comparative analysis of dosimetric and
      treatment delivery parameters.
AB  - PURPOSE: To compare dosimetric and treatment delivery parameter differences
      between volumetric-modulated arc radiotherapy (VMAT) and intensity-modulated
      radiotherapy (IMRT) for large volume retroperitoneal sarcomas (RPS). MATERIALS
      AND METHODS: Both VMAT and IMRT planning were performed on CT datasets of 10
      patients with RPS who had been previously treated with preoperative radiotherapy.
      Plans were optimized to deliver >=95% dose to the PTV and were evaluated for
      conformity and homogeneity. Dose to the organs at risk (OARs) (kidney, liver,
      spinal cord, and bowel space), unspecified tissue, and dose evaluation volumes
      (DEVs) at 1, 2, and 5 cm from PTV were calculated and compared. Monitor units
      (MUs) and treatment delivery times were recorded and compared between the two
      techniques. The deliverability of the large volume RPS VMAT plans was verified by
      portal dosimetry on a TruebeamTM linac. RESULTS: VMAT and IMRT plans were
      equivalent for PTV coverage and homogeneity (P > 0.05); however, VMAT plans had
      slightly better conformity index, CI (P < 0.001). Doses to the OARs were not
      significantly different between VMAT and IMRT plans (P > 0.05). Mean doses to the
      unspecified tissue as well as at 1, 2, and 5 cm DEVs were lower with VMAT
      compared with IMRT, P = 0.04 and P < 0.01, respectively. MUs and average beam-on
      times were both significantly lower in the VMAT vs IMRT plans, P < 0.001 and P =
      0.001, respectively. All VMAT plans passed portal dosimetry delivery verification
      with an average gamma passing rate of 99.6 +/- 0.4%. CONCLUSIONS: VMAT planning
      for large volume RPS improved CI, and achieved comparable OAR sparing, as
      compared with IMRT. As treatment delivery time was lower, the use of VMAT for RPS
      may translate into improved treatment delivery efficiency.

PMID- 29178587
TI  - Self-clotting method improves cell block preparation.
AB  - BACKGROUND: The success of cell block preparation is crucial for ancillary
      diagnostic tests in cytology. However, achieving an optimal cell block can be
      challenging. The current study describes a self-clotting-based technique for fine
      needle aspiration (FNA) cell block preparations and evaluates its usefulness in
      comparison with the conventional needle wash technique. METHODS: The clinical
      data, FNA procedure, and cellularity of cell blocks of the self-clotting group
      (37 cases) and the conventional needle wash group (33 cases) were compared. The
      cellularity was evaluated using a scoring system (0 indicated acellular, 1
      indicated 1-50 cells, and 2 indicated >50 cells). RESULTS: Approximately 76% of
      cases in the self-clotting group received a score of 2 versus 36% in the
      conventional needle wash group. Approximately 14% received a score of 1 in the
      self-clotting group compared with 9% in the conventional needle wash group,
      whereas 11% in the self-clotting group received a score of 0 versus 55% in the
      conventional needle wash group. The differences between the 2 methods were
      statistically significant. CONCLUSIONS: The results of the current study
      demonstrate that the self-clotting method is superior to the conventional needle
      wash method for FNA samples. Cancer Cytopathol 2018;126:190-9. (c) 2017 American
      Cancer Society.

PMID- 29178589
TI  - Liquid-Phase Transmission Electron Microscopy for Studying Colloidal Inorganic
      Nanoparticles.
AB  - For the past few decades, nanoparticles of various sizes, shapes, and
      compositions have been synthesized and utilized in many different applications.
      However, due to a lack of analytical tools that can characterize structural
      changes at the nanoscale level, many of their growth and transformation processes
      are not yet well understood. The recently developed technique of liquid-phase
      transmission electron microscopy (TEM) has gained much attention as a new tool to
      directly observe chemical reactions that occur in solution. Due to its high
      spatial and temporal resolution, this technique is widely employed to reveal
      fundamental mechanisms of nanoparticle growth and transformation. Here, the
      technical developments for liquid-phase TEM together with their application to
      the study of solution-phase nanoparticle chemistry are summarized. Two types of
      liquid cells that can be used in the high-vacuum conditions required by TEM are
      discussed, followed by recent in situ TEM studies of chemical reactions of
      colloidal nanoparticles. New findings on the growth mechanism, transformation,
      and motion of nanoparticles are subsequently discussed in detail.

PMID- 29178588
TI  - Early barriers to neonatal porcine islet engraftment in a dual transplant model.
AB  - Porcine islet xenografts have the potential to provide an inexhaustible source of
      islets for beta cell replacement. Proof-of-concept has been established in
      nonhuman primates. However, significant barriers to xenoislet transplantation
      remain, including the poorly understood instant blood-mediated inflammatory
      reaction and a thorough understanding of early xeno-specific immune responses. A
      paucity of data exist comparing xeno-specific immune responses with alloislet
      (AI) responses in primates. We recently developed a dual islet transplant model,
      which enables direct histologic comparison of early engraftment immunobiology. In
      this study, we investigate early immune responses to neonatal porcine islet (NPI)
      xenografts compared with rhesus islet allografts at 1 hour, 24 hours, and 7 days.
      Within the first 24 hours after intraportal infusion, we identified greater
      apoptosis (caspase 3 activity and TUNEL [terminal deoxynucleotidyl transferase
      dUTP nick end labeling])-positive cells) of NPIs compared with AIs. Macrophage
      infiltration was significantly greater at 24 hours compared with 1 hour in both
      NPI (wild-type) and AIs. At 7 days, IgM and macrophages were highly specific for
      NPIs (alpha1,3-galactosyltransferase knockout) compared with AIs. These findings
      demonstrate an augmented macrophage and antibody response toward xenografts
      compared with allografts. These data may inform future immune or genetic
      manipulations required to improve xenoislet engraftment.

PMID- 29178591
TI  - Complementarity of stability patches at the interfaces of protein complexes:
      Implication for the structural organization of energetic hot spots.
AB  - A rational design of protein complexes with defined functionalities and of drugs
      aimed at disrupting protein-protein interactions requires fundamental
      understanding of the mechanisms underlying the formation of specific protein
      complexes. Efforts to develop efficient small-molecule or protein-based binders
      often exploit energetic hot spots on protein surfaces, namely, the interfacial
      residues that provide most of the binding free energy in the complex. The
      molecular basis underlying the unusually high energy contribution of the hot
      spots remains obscure, and its elucidation would facilitate the design of
      interface-targeted drugs. To study the nature of the energetic hot spots, we
      analyzed the backbone dynamic properties of contact surfaces in several protein
      complexes. We demonstrate that, in most complexes, the backbone dynamic
      landscapes of interacting surfaces form complementary "stability patches," in
      which static areas from the opposing surfaces superimpose, and that these areas
      are predominantly located near the geometric center of the interface. We propose
      that a diminished enthalpy-entropy compensation effect augments the degree to
      which residues positioned within the complementary stability patches contribute
      to complex affinity, thereby giving rise to the energetic hot spots. These
      findings offer new insights into the nature of energetic hot spots and the role
      that backbone dynamics play in facilitating intermolecular recognition. Mapping
      the interfacial stability patches may provide guidance for protein engineering
      approaches aimed at improving the stability of protein complexes and could
      facilitate the design of ligands that target complex interfaces.

PMID- 29178590
TI  - Meloxicam inhibits biofilm formation and enhances antimicrobial agents efficacy
      by Pseudomonas aeruginosa.
AB  - Microbial biofilms are communities of surface-adhered cells enclosed in a matrix
      of extracellular polymeric substances. Bacterial cells in biofilm are 10~1,000
      fold more resistant to antimicrobials than the planktonic cells. Burgeoning
      antibiotic resistance in Pseudomonas aeruginosa biofilm has necessitated the
      development of antimicrobial agents. Here, we have investigated the antibiofilm
      effect of meloxicam against P. aeruginosaPAO1 and its potential mechanisms.
      Further, we have explored whether meloxicam could enhance the susceptibility of
      bacterial biofilms to treatment with conventional antimicrobials. Here, we found
      that meloxicam could significantly inhibit PAO1 biofilm formation in a dose
      dependent manner at the concentration without influence on planktonic cell
      growth. Meloxicam could also significantly inhibit the motilities, production of
      extracellular matrix, and expression of quorum sensing-related genes and
      virulence factors of PAO1. Furthermore, synergistic interaction was observed when
      meloxicam combined with tetracycline, gentamicin, tobramycin, ciprofloxacin,
      ceftriaxone, ofloxacin, norfloxacin, ceftazidime, and DNase at subminimal
      inhibitory concentrations against PAO1 bioiflm. Collectively, our study lays the
      foundation for further investigation of repurposing meloxicam as a topical
      antibiofilm agent to treat P. aeruginosa biofilm-related infections.

PMID- 29178592
TI  - A 3D Covalent Organic Framework with Exceptionally High Iodine Capture
      Capability.
AB  - Using porous materials to cope with environmental issues is promising but remains
      a challenge especially for removing the radioactive vapor wastes in fission
      because of harsh adsorption conditions. Here we report a new, stable covalent
      organic framework (COF) as a porous platform for removing iodine vapor-a major
      radioactive fission waste. The three-dimensional COF consists of a diamond
      topology knotted by adamantane units, creates ordered one-dimensional pores and
      are highly porous. The COF enables the removal of iodine vapor via charge
      transfer complex formation with the pore walls to achieve exceptional capacity.
      Moreover, the 3D COF is "soft" to trigger structural fitting to iodine while
      retaining connectivity and enables cycle use for many times while retaining high
      uptake capacity. These results set a new benchmark for fission waste removal and
      suggest the great potential of COFs as a designable porous material for
      challenging world-threatening pollution issues.

PMID- 29178593
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 49/2017.

PMID- 29178594
TI  - Cu(OAc)2 /TEMPO Cooperative Promoted Hydroamination Cyclization and Oxidative
      Dehydrogenation Cascade Reaction of Homopropargylic Amines.
AB  - A novel and efficient Cu(OAc)2 -catalyzed hydroamination cyclization and 2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidative dehydrogenation cascade
      reaction of homopropargylic amines has been developed. A library of 1,2
      disubstituted pyrrole derivatives were obtained in good-to-high yields in one pot
      with no step-by-step feeding process. This reaction involved TEMPO playing dual
      roles as both an oxidative dehydrogenation reagent and a ligand. An insight into
      the reaction mechanism was obtained by using several analytical determination
      methods.

PMID- 29178595
TI  - A simplified Monte Carlo algorithm considering large-angle scattering for fast
      and accurate calculation of proton dose.
AB  - PURPOSE: The purpose of this study is to improve dose calculation accuracy of the
      simplified Monte Carlo (SMC) algorithm in the low-dose region. Because
      conventional SMC algorithms calculate particle scattering in consideration of
      multiple Coulomb scattering (MCS) only, they approximate lateral dose profiles by
      a single Gaussian function. However, it is well known that the low-dose region
      spreads away from the beam axis, and it has been pointed out that modeling of the
      low-dose region is important to calculated dose accurately. METHODS: A SMC
      algorithm, which is named modified SMC and considers not only MCS but also large
      angle scattering resembling hadron elastic scattering, was developed. In the
      modified SMC algorithm, the particle fluence varies in the longitudinal direction
      because the large-angle scattering decreases residual range of particles in
      accordance with their scattering angle and tracking of the particles with large
      scattering angle is terminated at a short distance downstream from the
      scattering. Therefore, modified integrated depth dose (m-IDD) tables, which are
      converted from measured IDD in consideration of the fluence loss, are used to
      calculate dose. RESULTS: In the case of a 1-liter cubic target, the calculation
      accuracy was improved in comparison with that of a conventional algorithm, and
      the modified algorithm results agreed well with Geant4-based simulation results;
      namely, 98.8% of the points satisfied the 2% dose/2 mm distance-to-agreement
      (DTA) criterion. The calculation time of the modified SMC algorithm was 1972 s in
      the case of 4.4 * 108 particles and 16-threading operation of an Intel Xeon E5
      2643 (3.3-GHz clock). CONCLUSIONS: An SMC algorithm that can reproduce a
      laterally widespread low-dose region was developed. According to the comparison
      with a Geant4-based simulation, it was concluded that the modified SMC algorithm
      is useful for calculating dose of proton radiotherapy.

PMID- 29178596
TI  - Knowledge and attitudes toward transgender health.
AB  - BACKGROUND: Hormonal interventions for transgender adolescents have become
      increasingly common; however, there is a paucity of research on medical student
      knowledge of, and attitudes toward, these interventions following didactic
      instruction. Furthermore, no studies have examined whether students can be aware
      of the literature on the mental health benefits of these treatments yet continue
      to find them unethical. METHODS: An anonymous online survey was administered to
      students, from first to fourth year (n = 407), who had received one or two
      lectures on the treatment of youths with gender dysphoria (GD). RESULTS: Surveys
      were completed by 162 respondents (40%). A majority was able to correctly answer
      questions regarding psychiatric co-morbidities, diagnostic criteria, hormonal
      interventions, long-term benefits of interventions and terminology. There was
      some evidence that precision in the use of terminology waned over time. Many were
      unclear on the role of puberty blockers and the time requirement for a diagnosis
      of GD. A minority (14%) reported a belief that hormonal therapy is unethical,
      although these same individuals recognised that these treatments have mental
      health benefits. DISCUSSION: Our results have implications for future
      instruction, including: the need to teach pharmacological and diagnostic issues
      more deliberately; providing refresher training on terminology; and relying on
      interactive discussion or patient visits, rather than didactic lectures alone,
      for ethically charged medical topics. Similar levels of knowledge among students
      who believe that hormonal therapy is ethical and unethical may indicate that
      imparting didactic knowledge about therapeutic benefits alone may not be
      sufficient to affect attitudes regarding endocrine care for transgender youth.
      Hormonal interventions for transgender adolescents have become increasingly
      common.

PMID- 29178598
TI  - Workplace bullying and burnout among healthcare employees: The moderating effect
      of control-related resources.
AB  - Workplace bullying is a widespread and challenging problem in healthcare
      organizations, bearing negative consequences for individuals and organizations.
      Drawing on the job demands-resources theory, in this study, we examined the
      relationship between workplace bullying and burnout among healthcare employees,
      as well as the moderating role of job autonomy and occupational self-efficacy in
      this relationship. Using a cross-sectional design with anonymous questionnaires,
      data were collected from two samples of 309 healthcare employees in a mental
      health facility, and 105 nurses studying for their bachelor degree in health
      systems administration. The findings indicated that workplace bullying was
      positively related to burnout dimensions, and that this relationship was
      moderated by job autonomy and occupational self-efficacy resources. Job autonomy
      interacted with workplace bullying in predicting emotional exhaustion and
      depersonalization; the interaction of bullying with occupational self-efficacy
      significantly predicted depersonalization. These results underscore the
      importance of control-related resources in mitigating the harmful effects of
      workplace bullying on employees. Implications for research and managerial
      practices are discussed.

PMID- 29178597
TI  - Body size and allometric variation in facial shape in children.
AB  - OBJECTIVES: Morphological integration, or the tendency for covariation, is
      commonly seen in complex traits such as the human face. The effects of growth on
      shape, or allometry, represent a ubiquitous but poorly understood axis of
      integration. We address the question of to what extent age and measures of size
      converge on a single pattern of allometry for human facial shape. METHODS: Our
      study is based on two large cross-sectional cohorts of children, one from
      Tanzania and the other from the United States (N = 7,173). We employ 3D facial
      imaging and geometric morphometrics to relate facial shape to age and
      anthropometric measures. RESULTS: The two populations differ significantly in
      facial shape, but the magnitude of this difference is small relative to the
      variation within each group. Allometric variation for facial shape is similar in
      both populations, representing a small but significant proportion of total
      variation in facial shape. Different measures of size are associated with
      overlapping but statistically distinct aspects of shape variation. Only half of
      the size-related variation in facial shape can be explained by the first
      principal component of four size measures and age while the remainder associates
      distinctly with individual measures. CONCLUSIONS: Allometric variation in the
      human face is complex and should not be regarded as a singular effect. This
      finding has important implications for how size is treated in studies of human
      facial shape and for the developmental basis for allometric variation more
      generally.

PMID- 29178599
TI  - Gut Microbiome-Induced Shift of Acetate to Butyrate Positively Manages Dysbiosis
      in High Fat Diet.
AB  - SCOPE: A recent study revealed that the accumulation of gut microbiota-produced
      acetate (GMPA) led to insulin over-secretion and obesity symptom. To further
      develop this scientific point, the effect of resistant starch (RS) or exogenous
      acetate carried by RS (RSA) in the gut on metabolic syndrome is investigated
      using diet-induced obese rats. METHODS AND RESULTS: The metabonomics analysis
      shows that the gut of rats in the RSA group generate more butyrate in both serum
      and feces rather than acetate compared to the rats in RS group, indicating the
      conversion among metabolites, in particular from acetate to butyrate via gut
      microbiota. Consistently, the gut microbiome uses acetate as a substrate to
      produce butyrate, such as Coprococcus, Faecalibacterium, Roseburia, and
      Eubacterium and was highly promoted in RSA group, which further supports the
      metabolic conversion. This is the first report to reveal the accumulation of gut
      microbiota-produced butyrate (GMPB) but not GMPA significantly enriched AMPK
      signaling pathway with reduced expression of lipogenesis-associated genes for
      suppressing sphingosines and ceramides biosynthesis to trigger insulin
      sensitivity. CONCLUSION: Gut microbiome profile and lipogenesis pathway are
      regulated by GMPB, which substantially influences energy harvesting in the gut
      from patterns opposed to GMPA.

PMID- 29178600
TI  - Genetic Markers of Brown Adipose Tissue Identity and In Vitro Brown Adipose
      Tissue Activity in Humans.
AB  - OBJECTIVE: Human brown adipose tissue (BAT) activity decreases with age and
      obesity. In addition to uncoupling protein 1 (UCP1), several genetic markers of
      BAT in humans have been published. However, the link between human BAT activity
      and genetic markers has been inadequately explored. METHODS: White adipose tissue
      (WAT) and BAT biopsies were obtained from 16 patients undergoing deep neck
      surgery. In vitro differentiated adipocytes were used to measure norepinephrine
      stimulated mitochondrial uncoupling as a measure of in vitro BAT activity. Gene
      expression was determined in adipose tissue biopsies. RESULTS: Norepinephrine
      increased in vitro BAT activity in adipocytes derived from human BAT, and this
      increase was abolished by propranolol. Furthermore, in vitro BAT activity showed
      a negative correlation to age and BMI. UCP1 messenger RNA (mRNA) expression
      showed a positive correlation to in vitro BAT activity, while zinc finger protein
      of cerebellum 1 (ZIC1) mRNA showed a negative correlation to in vitro BAT
      activity. In human BAT biopsies, UCP1 mRNA showed negative correlations to age
      and BMI, while ZIC1 mRNA showed positive correlations to age and BMI.
      CONCLUSIONS: Differentiated adipocytes derived from human BAT maintain intrinsic
      characteristics of the donor. High ZIC1 mRNA does not necessarily reflect high
      BAT activity.

PMID- 29178601
TI  - The prevalence, risk factors, and outcomes of medication trade-offs in kidney and
      liver transplant recipients: a pilot study.
AB  - High out-of-pocket medication costs negatively impact adherence in
      transplantation. We evaluated the association of "medication trade-offs"-defined
      as choosing to spend money on other expenses over medications-with medication
      nonadherence and transplant outcomes. From 2011 to 2012, we performed a
      prospective study of 201 transplanted recipients (n = 103 liver, n = 98 kidney
      and) at two large US transplant centers. Structured interviews assessed socio
      demographics, medication adherence, and medication trade-offs. Multivariable
      models assessing risk factors for medications trade-offs and the association
      between medications trade-offs and post-transplant hospital admissions were
      performed. A total of 17% of patients reported medication trade-offs; the most
      common trade-offs were inability to afford a prescription in the past 12 months
      and making choices between prescriptions and food. In multivariable analysis,
      insurance type (RR: 2.97, 95% CI: 1.19-7.40), limited health literacy (RR: 2.64,
      95% CI: 1.23-5.64), and >=3 comorbid conditions (RR: 2.48, 95% CI: 1.09-5.62; all
      P < 0.05) were associated with trade-offs. Patients with trade-offs were more
      likely to report nonadherence to medications (mean adherence: 77 +/- 23% with
      trade-offs vs. 89 +/- 19% without trade-offs, P < 0.01). The presence of
      medication trade-offs was associated with post-transplant hospital admissions (RR
      1.64, 95% CI 1.14-2.35, P < 0.01). Assessments of financial barriers are
      warranted in clinical practice to identify nonadherence and improve post
      transplant outcomes.

PMID- 29178602
TI  - Should consultation recording use be a practice standard? A systematic review of
      the effectiveness and implementation of consultation recordings.
AB  - OBJECTIVE: To conduct a systematic review of the effectiveness of consultation
      recordings and identify factors contributing to their successful implementation
      in health-care settings. METHODS: A systematic review was conducted for
      quantitative studies examining the effectiveness of consultation recordings in
      health care. Two independent reviewers assessed the relevance and quality of
      retrieved quantitative studies by using standardized criteria. Study findings
      were examined to determine consultation recording effectiveness and to identify
      barriers and facilitators to implementation. A supplementary review of
      qualitative evidence was performed to further explicate implementation factors.
      RESULTS: Of the 3373 articles retrieved in the quantitative search, 26 satisfied
      the standardized inclusion criteria (12 randomized controlled trials, 1 quasi
      experiment, and 13 cross-sectional studies). Most patients found consultation
      recordings beneficial. Statistically significant evidentiary support was found
      for the beneficial impact of consultation recordings on the following patient
      reported outcomes: knowledge, perception of being informed, information recall,
      decision-making factors, anxiety, and depression. Implementation barriers
      included strength of evidence concerns, patient distress, impact of the recording
      on consultation quality, clinic procedures, medico-legal issues, and resource
      costs. Facilitators included comfort with being recorded, clinical champions,
      legal strategies, efficient recording procedures, and a positive consultation
      recording experience. CONCLUSIONS: Consultation recordings are valuable to
      patients and positively associated with patient-reported outcomes. Successful
      integration of consultation recording use into clinical practice requires an
      administratively supported, systematic approach to addressing implementation
      factors.

PMID- 29178603
TI  - Targeted next-generation sequencing and parental genotyping in sporadic Chinese
      Han deaf patients.
AB  - The interpretation of the targeted next-generation sequencing (NGS) results can
      be challenging for variants identified in the sporadic deaf patients. In this
      study, we performed targeted NGS of 143 deafness-associated genes in 44 sporadic
      deaf patients and use parental genotyping to test whether the candidate
      pathogenic variants complied with recessive or de novo pattern. Of 29 recessive
      candidate variants with minor allele frequencies (MAFs) less than 0.005, 3 pairs
      of apparent compound heterozygous variants were inherited from the same parental
      allele, ruling out their pathogenic roles. In addition, non-segregation of an
      OTOA p.Gln293Arg variant led to the discovery of a genomic microdeletion of OTOA
      on the opposite allele by copy number variation analysis. Overall, 13 pairs of
      recessive candidate variants were deemed causative in 13 patients. Of the 28
      dominant candidate variants with MAFs less than 0.0005, none occurred de novo,
      suggesting that they were not disease causing. Our results revealed that targeted
      NGS in sporadic deaf patients may generate a significant false-positive rate.
      Parental genotyping is a simple but effective step toward minimizing the false
      positive results. Our study also showed that de novo variants in dominant
      deafness genes may not be a common cause for sporadic deafness.

PMID- 29178604
TI  - Examining polyquaternium polymers deposition on human excised hair fibers.
AB  - BACKGROUND: Polyquaterniums (PQs) as important ingredients of hair products are
      synthetic cationic polymers and are used in commercial hair volumizers and
      conditioners. METHODS: Three different grades of polymers including PQ 87, 68,
      and 46 with various concentrations were used, and their hair deposition efficacy
      was measured at 5 different pH values using hair diameters measurements by
      digital micrometer. Deposition durability of polymer layer on the hair surface
      was tested by a defined washing test. Optical microscopic images and polarized
      light images were also taken from treated and untreated samples for further
      investigation. Attenuated total reflectance (ATR) spectral were recorded from
      hair samples to prove the polymer deposition and probable interaction with hair
      fibers. RESULTS: PQ-68 with the highest molecular weight (300 kDa) at pH = 9
      exhibited the best hair deposition efficacy. The results revealed that the
      deposition of polymers is directly proportional to the pH values. The best
      results were seen at pH = 9, and at the lowest pH (pH = 5), the efficiency of
      polymers was approximately equal to zero. The best resistance against washing was
      shown by PQ-44 at pH = 6. ATR successfully tracked the presence of the polymers
      on the hair fibers and also proposed specific wave numbers for each polymeric
      agent, individually. CONCLUSIONS: In general, two main parameter which can mainly
      influence the deposition efficacy of PQs are the type of polymer or its molecular
      weight and also the positive charge density on the polymer molecules.

PMID- 29178605
TI  - RECORDS: improved Reporting of montE CarlO RaDiation transport Studies: Report of
      the AAPM Research Committee Task Group 268.
AB  - Studies involving Monte Carlo simulations are common in both diagnostic and
      therapy medical physics research, as well as other fields of basic and applied
      science. As with all experimental studies, the conditions and parameters used for
      Monte Carlo simulations impact their scope, validity, limitations, and
      generalizability. Unfortunately, many published peer-reviewed articles involving
      Monte Carlo simulations do not provide the level of detail needed for the reader
      to be able to properly assess the quality of the simulations. The American
      Association of Physicists in Medicine Task Group #268 developed guidelines to
      improve reporting of Monte Carlo studies in medical physics research. By
      following these guidelines, manuscripts submitted for peer-review will include a
      level of relevant detail that will increase the transparency, the ability to
      reproduce results, and the overall scientific value of these studies. The
      guidelines include a checklist of the items that should be included in the
      Methods, Results, and Discussion sections of manuscripts submitted for peer
      review. These guidelines do not attempt to replace the journal reviewer, but
      rather to be a tool during the writing and review process. Given the varied
      nature of Monte Carlo studies, it is up to the authors and the reviewers to use
      this checklist appropriately, being conscious of how the different items apply to
      each particular scenario. It is envisioned that this list will be useful both for
      authors and for reviewers, to help ensure the adequate description of Monte Carlo
      studies in the medical physics literature.

PMID- 29178606
TI  - Empowering students with the hidden curriculum.
AB  - BACKGROUND: The hidden curriculum (HC) refers to unscripted, ad hoc learning that
      occurs outside the formal, taught curriculum and can have a powerful influence on
      the professional development of students. While this learning may be positive, it
      may conflict with that taught in the formal curriculum. Medical schools take a
      range of steps to address these negative effects; however, the existence and
      nature of the concept tends to be hidden from students. METHODS: Since 2007, our
      medical school has incorporated into its small group programme an educational
      activity exploring the concept of the hidden curriculum. We undertook a
      qualitative evaluation of our intervention, conducting a thematic analysis of
      students' wiki reflections about the HC. We also analysed students' responses to
      a short questionnaire about the educational approach used. FINDINGS: The majority
      of students felt that the HC session was important and relevant. Most appeared
      able to identify positive and negative HC experiences and consider how these
      might influence their learning and development, although a few students found the
      concept of the HC hard to grasp. DISCUSSION: Revealing and naming the hidden
      curriculum can make students aware of its existence and understand its potential
      impact. The hidden curriculum may also be a useful tool for triggering debate
      about issues such as power, patient centredness, personal resilience and career
      stereotypes in medicine. Supporting students to think critically about HC
      experiences may empower them to make active choices about which messages to take
      on board. The hidden curriculum can have a powerful influence on the professional
      development of students.

PMID- 29178607
TI  - Detection and clinical impact of human leukocyte antigen antibodies in lung
      transplantation: A systematic review and meta-analysis.
AB  - There is significant variability in lung transplant centers' approach to HLA
      antibodies, creating heterogeneity regarding their clinical significance. Some
      institutions use beads coated with multiple HLA to screen candidate sera and then
      use single antigen bead (SAB) to determine antibody identity if the pre-screen is
      positive. Other centers do not pre-screen, using SAB alone, which may detect low
      level antibodies of unknown significance. The primary objective of this study was
      to review the current literature to identify sources of heterogeneity in the
      identification of pre- and post-lung transplant HLA antibodies, particularly
      regarding antibody-detection methods. A random effects model meta-analysis was
      used to evaluate the relationship between pre-transplant HLA antibodies and the
      development of de novo donor-specific antibodies (dnDSA) and dnDSA and chronic
      lung allograft dysfunction (CLAD). Each outcome was stratified by the method of
      antibody detection (pre-screen followed by SAB vs SAB alone). We identified 13
      cohort studies with a total of 3039 patients. The use of pre-screening followed
      by SAB testing and the use of induction immunosuppression were associated with
      lower prevalence of dnDSA. Patients with pre-transplant HLA antibodies were more
      likely to develop dnDSA (hazard ratio [HR] = 1.49, 95% confidence interval [CI]:
      1.19-1.86, P < .001). dnDSA was associated with CLAD (HR = 2.02, 95% CI = 1.37
      2.97, P < .001). When considering studies using SAB alone, however, pre
      transplant antibody status was no longer associated with dnDSA and dnDSA was no
      longer associated with CLAD. Based on the current literature, SAB-alone testing
      may detect less clinically relevant antibodies than pre-screening followed by
      SAB.

PMID- 29178608
TI  - Molecular investigation of 41 patients affected by coagulation factor XI
      deficiency.

PMID- 29178609
TI  - Phosphonate-Mediated Immobilization of Rhodium/Bipyridine Hydrogenation
      Catalysts.
AB  - RhL2 complexes of phosphonate-derivatized 2,2'-bipyridine (bpy) ligands L were
      immobilized on titanium oxide particles generated in situ. Depending on the
      structure of the bipy ligand-number of tethers (1 or 2) to which the phosphonate
      end groups are attached and their location on the 2,2'-bipyridine backbone (4,4'
      , 5,5'-, or 6,6'-positions)-the resulting supported catalysts showed comparable
      chemoselectivity but different kinetics for the hydrogenation of 6-methyl-5
      hepten-2-one under hydrogen pressure. Characterization of the six supported
      catalysts suggested that the intrinsic geometry of each of the phosphonate
      derivatized 2,2'-bipyridines leads to supported catalysts with different
      microstructures and different arrangements of the RhL2 species at the surface of
      the solid, which thereby affect their reactivity.

PMID- 29178611
TI  - Influence of Images on the Evaluation of Jams Using Conjoint Analysis Combined
      with Check-All-That-Apply (CATA) Questions.
AB  - A study of the influence of the use of images in a conjoint analysis combined
      with check-all-that apply (CATA) questions on jams was carried out. The relative
      importance of flavor and the information presented in the label in the
      willingness to purchase and the perception of how healthy the product is has been
      evaluated. Sixty consumers evaluated the stimuli presented only in text format
      (session 1), and another group of 60 consumers did so by receiving the stimuli in
      text format along with an image of the product (session 2). In addition, for each
      stimulus, consumers answered a CATA question consisting of 20 terms related to
      their involvement with the product. The perception of healthy increased when the
      texts were accompanied with images and also increased when the text included
      information. Willingness to purchase was only influenced by the flavor of the
      jams. The presence of images did not influence the CATA question's choice of
      terms, which were influenced by the information presented in the text. The use of
      a check-all-that-apply question in concepts provided an interesting possibility
      when they were combined with the results from the conjoint analysis, improving
      the comprehension of consumers' perception. Using CATA questions as an
      alternative way of evaluating consumer involvement seems to be beneficial and
      should be evaluated much further.

PMID- 29178610
TI  - Evidence of porcine circovirus-like virus P1 in piglets with an unusual
      congenital tremor.
AB  - Outbreaks of trembling and shaking were reported among pigs at two pig farms in
      Jiangsu Province, China. Serum and tissue samples tested positive for porcine
      circovirus-like virus P1 and negative for classical swine fever virus, porcine
      circovirus type 2, astrovirus and porcine pestivirus using PCR/RT-PCR and
      immunohistochemical techniques. High P1 viral genome loads were identified in
      sera, brain and lymph node tissue samples by qPCR. In addition, one of the most
      notable pathological changes was dissolution of the nucleus in Purkinje cells.
      The results of this study provide molecular evidence of an association between
      congenital tremor in pigs and P1 virus.

PMID- 29178612
TI  - Identification of a sugar gustatory receptor and its effect on fecundity of the
      brown planthopper Nilaparvata lugens.
AB  - In insects, the gustatory system plays a crucial role in multiple physiological
      behaviors, including feeding, toxin avoidance, courtship, mating and oviposition.
      Gustatory stimuli from the environment are recognized by gustatory receptors. To
      date, little is known about the function of gustatory receptors in agricultural
      pest insects. In this study, we cloned a sugar gustatory receptor gene, NlGr11,
      from the brown planthopper (BPH), Nilaparvata lugens (Stal), a serious pest of
      rice in Asia; we then identified its ligands, namely, fructose, galactose and
      arabinose, by calcium imaging assay. After injection of NlGr11 double-stranded
      RNA, we found that the number of eggs laid by BPH decreased. Moreover, we found
      that NlGr11 inhibited the phosphorylation of adenosine monophosphate-activated
      protein kinase (AMPK) and promoted the phosphorylation of protein kinase B (AKT).
      These findings demonstrated that NlGr11 could accelerate the fecundity of BPH
      through AMPK- and AKT-mediated signaling pathways. This is the first report to
      indicate that a gustatory receptor modulates the fecundity of insects and that
      the receptor could be a potential target for pest control.

PMID- 29178613
TI  - Aging mechanisms and intervention targets.
AB  - Premature aging occurs frequently to various tissues and organs resulting in the
      tissue-specific chronic diseases. The mechanisms of tissue-specific premature
      aging are largely unknown. In response to environmental cues, aging may originate
      from cytoplasm or the nucleus of a cell with cytoplasm aging in association with
      organelle degeneration in terminally differentiated cells and nuclear aging with
      dysfunctional telomeres and irreversible cell cycle arrest in stem and cancer
      cells. Either cytoplasm aging or nuclear aging may cause extracellular senescence
      associated low-grade inflammation to spread aging. Referring to the recent
      findings in this special issue of Healthy Aging in CEPP and beyond, we describe
      the molecular and cellular mechanisms of physiological aging and tissue-specific
      pathological aging in chronic diseases.

PMID- 29178614
TI  - Antibacterial activity of chitosan against Burkholderia pseudomallei.
AB  - The ability of Burkholderia pseudomallei to persist and survive in the
      environment is a health problem worldwide. Therefore, the antibacterial
      activities of chitosan against four environmental isolates of B. pseudomallei
      from soil in Khon Kaen, Thailand, were investigated. Antibacterial activities
      were assessed by a plate count technique after treatment with 0.2, 0.5, 1, 2 or 5
      mg ml-1 chitosan for 0, 24 and 48 hr. Chitosan at 5 mg ml-1 completely killed all
      four B. pseudomallei isolates within 24 hr, whilst 2 mg ml-1 chitosan lowered the
      viability of B. pseudomallei by 20% within the same time span. Chitosan may act
      by disruption of the cell membrane, releasing intracellular components that can
      be detected spectrophotometrically at 260 and 280 nm. Transmission electron
      microscopy inspection of chitosan-treated B. pseudomallei revealed damage to the
      bacterial membranes. This study demonstrated the effective antibacterial activity
      by chitosan against B. pseudomallei. Chitosan causes disruption of the bacterial
      cell membrane, release of intracellular constituents and cell death. This study
      revealed the inhibitory potential of chitosan for mitigating B. pseudomallei
      occurrences.

PMID- 29178615
TI  - Plant organ senescence - regulation by manifold pathways.
AB  - Senescence is the final stage of plant ontogeny before death. Senescence may
      occur naturally because of age or may be induced by various endogenous and
      exogenous factors. Despite its destructive character, senescence is a precisely
      controlled process that follows a well-defined order. It is often inseparable
      from programmed cell death (PCD), and a correlation between these processes has
      been confirmed during the senescence of leaves and petals. Despite suggestions
      that senescence and PCD are two separate processes, with PCD occurring after
      senescence, cell death responsible for senescence is accompanied by numerous
      changes at the cytological, physiological and molecular levels, similar to other
      types of PCD. Independent of the plant organ analysed, these changes are focused
      on initiating the processes of cellular structural degradation via fluctuations
      in phytohormone levels and the activation of specific genes. Cellular structural
      degradation is genetically programmed and dependent on autophagy.
      Phytohormones/plant regulators are heavily involved in regulating the senescence
      of plant organs and can either promote [ethylene, abscisic acid (ABA), jasmonic
      acid (JA), and polyamines (PAs)] or inhibit [cytokinins (CKs)] this process.
      Auxins and carbohydrates have been assigned a dual role in the regulation of
      senescence, and can both inhibit and stimulate the senescence process. In this
      review, we introduce the basic pathways that regulate senescence in plants and
      identify mechanisms involved in controlling senescence in ephemeral plant organs.
      Moreover, we demonstrate a universal nature of this process in different plant
      organs; despite this process occurring in organs that have completely different
      functions, it is very similar. Progress in this area is providing opportunities
      to revisit how, when and which way senescence is coordinated or decoupled by
      plant regulators in different organs and will provide a powerful tool for plant
      physiology research.

PMID- 29178616
TI  - Diffusion-weighted MRI characteristics associated with prognostic pathological
      factors and recurrence risk in invasive ER+/HER2- breast cancers.
AB  - BACKGROUND: Hormone receptor-positive breast cancer is the most common subtype;
      better tools to identify which patients in this group would derive clear benefit
      from chemotherapy are needed. PURPOSE: To evaluate the prognostic potential of
      diffusion-weighted MRI (DWI) by investigating associations with pathologic
      biomarkers and a genomic assay for 10-year recurrence risk. STUDY TYPE:
      Retrospective. SUBJECTS: In all, 107 consecutive patients (from 2/2010 to 1/2013)
      with estrogen receptor (ER)-positive/HER2neu-negative invasive breast cancer who
      had the 21-gene recurrence score (RS) test (Oncotype DX, Genomic Health). FIELD
      STRENGTH/SEQUENCE: Each subject underwent presurgical 3T breast MRI, which
      included DWI (b = 0, 800 s/mm2 ). ASSESSMENT: Apparent diffusion coefficient
      (ADC) and contrast-to-noise ratio (CNR) were measured for each lesion by a fifth
      year radiology resident. Pathological markers (Nottingham histologic grade, Ki
      67, RS) were determined from pathology reports. Medical records were reviewed to
      assess recurrence-free survival. STATISTICAL TESTS: RS was stratified into low
      (<18), moderate (18-30), and high (>30)-risk groups. Associations of DWI
      characteristics with pathologic biomarkers were evaluated by binary or ordinal
      logistic regression, as appropriate, with adjustment for multiple comparisons.
      Post-hoc comparisons between specific groups were also performed. RESULTS:
      ADCmean (odds ratio [OR] = 0.61 per 1 standard deviation [SD] increase, adj. P =
      0.044) and CNR (OR = 1.76 per 1-SD increase, adj. P = 0.026) were significantly
      associated with increasing tumor grade. DWI CNR was also significantly associated
      with a high (Ki-67 >=14%) proliferation rate (OR = 2.55 per 1-SD increase, adj. P
      = 0.026). While there were no statistically significant linear associations in
      ADC (adj. P = 0.80-0.85) and CNR (adj. P = 0.56) across all three RS groups by
      ordinal logistic regression, post-hoc analyses suggested that high RS lesions
      exhibited lower ADCmean (P = 0.037) and ADCmax (P = 0.004) values and higher CNR
      (P = 0.008) compared to lesions with a low or moderate RS. DATA CONCLUSION: DWI
      characteristics correlated with tumor grade, proliferation index, and RS, and may
      potentially help to identify those with highest recurrence risk and most
      potential benefit from chemotherapy. LEVEL OF EVIDENCE: 3 Technical Efficacy
      Stage 3 J. Magn. Reson. Imaging 2017.

PMID- 29178617
TI  - Serum Lipid and Protein Changes in Healthy Dyslipidemic Subjects Given a
      Selective Inhibitor of p70 S6 Kinase-1.
AB  - The safety, pharmacokinetic, and pharmacodynamic effects of LY2584702, a
      selective inhibitor for p70 S6 serine/threonine protein kinase-1, were evaluated
      in healthy dyslipidemic volunteers. LY2584702 was tolerated well as a monotherapy
      and dose-dependently reduced low-density lipoprotein cholesterol and
      triglycerides by up to 60% and 50%, respectively, without significantly changing
      high-density lipoprotein cholesterol levels in plasma. LY2584702 also dose
      dependently decreased factor V activity. Alanine aminotransferase elevations were
      noted in 2 subjects when LY2584702 was given with atorvastatin. We suspect that
      the formation of 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) during metabolism may
      have contributed to some of the adverse effects of LY2584702, and the
      contribution of 4-APP to the pharmacology merits further investigation. Although
      clinical investigation of LY2584702 has been terminated because of hepatotoxicity
      risk, we suggest that a selective inhibitor of p70 S6 serine/threonine protein
      kinase-1 with a larger margin of safety and without the possibility of being
      metabolized to 4-APP may be useful in the treatment of dyslipidemia.

PMID- 29178618
TI  - A unified partial likelihood approach for X-chromosome association on time-to
      event outcomes.
AB  - The expression of X-chromosome undergoes three possible biological processes: X
      chromosome inactivation (XCI), escape of the X-chromosome inactivation (XCI-E),
      and skewed X-chromosome inactivation (XCI-S). Although these expressions are
      included in various predesigned genetic variation chip platforms, the X
      chromosome has generally been excluded from the majority of genome-wide
      association studies analyses; this is most likely due to the lack of a
      standardized method in handling X-chromosomal genotype data. To analyze the X
      linked genetic association for time-to-event outcomes with the actual process
      unknown, we propose a unified approach of maximizing the partial likelihood over
      all of the potential biological processes. The proposed method can be used to
      infer the true biological process and derive unbiased estimates of the genetic
      association parameters. A partial likelihood ratio test statistic that has been
      proved asymptotically chi-square distributed can be used to assess the X
      chromosome genetic association. Furthermore, if the X-chromosome expression
      pertains to the XCI-S process, we can infer the correct skewed direction and
      magnitude of inactivation, which can elucidate significant findings regarding the
      genetic mechanism. A population-level model and a more general subject-level
      model have been developed to model the XCI-S process. Finite sample performance
      of this novel method is examined via extensive simulation studies. An application
      is illustrated with implementation of the method on a cancer genetic study with
      survival outcome.

PMID- 29178619
TI  - Abasic Site-Assisted Inhibition of Nicking Endonuclease Activity for the
      Sensitive Determination of Uracil DNA Glycosylase.
AB  - We herein describe A novel strategy to accurately determine uracil DNA
      glycosylase (UDG) activity is described based on the finding that nicking
      endonuclease-assisted cleavage reaction can be regulated by the presence of
      abasic site. This strategy utilizes DNA probes rationally designed to contain
      uracil base at the cleavage site for nicking endonuclease, which is coupled to
      the isothermal nicking endonuclease amplification reaction (NEAR) method. In the
      absence of UDG, intact DNA probes generate a large number of double-stranded (ds)
      DNA products through the NEAR, but the presence of UDG that converts uracil base
      into abasic site suppresses nicking endonuclease activity and the subsequent
      NEAR. As a result, dsDNA products are not produced, which is simply monitored by
      the dsDNA specific fluorescence dye, SYBR green I. By employing this strategy, we
      sensitively determined the UDG activity down to 0.003 U mL-1 with high
      specificity over other base excision enzymes. In addition, the diagnostic
      capability of this method was successfully verified by reliably assaying UDG
      present in a human serum sample.

PMID- 29178620
TI  - Comparative genomics of Spiraeoideae-infecting Erwinia amylovora strains provides
      novel insight to genetic diversity and identifies the genetic basis of a low
      virulence strain.
AB  - Erwinia amylovora is the causal agent of fire blight, one of the most devastating
      diseases of apple and pear. Erwinia amylovora is thought to have originated in
      North America and has now spread to at least 50 countries worldwide. An
      understanding of the diversity of the pathogen population and the transmission to
      different geographical regions is important for the future mitigation of this
      disease. In this research, we performed an expanded comparative genomic study of
      the Spiraeoideae-infecting (SI) E. amylovora population in North America and
      Europe. We discovered that, although still highly homogeneous, the genetic
      diversity of 30 E. amylovora genomes examined was about 30 times higher than
      previously determined. These isolates belong to four distinct clades, three of
      which display geographical clustering and one of which contains strains from
      various geographical locations ('Widely Prevalent' clade). Furthermore, we
      revealed that strains from the Widely Prevalent clade displayed a higher level of
      recombination with strains from a clade strictly from the eastern USA, which
      suggests that the Widely Prevalent clade probably originated from the eastern USA
      before it spread to other locations. Finally, we detected variations in virulence
      in the SI E. amylovora strains on immature pear, and identified the genetic basis
      of one of the low-virulence strains as being caused by a single nucleotide
      polymorphism in hfq, a gene encoding an important virulence regulator. Our
      results provide insights into the population structure, distribution and
      evolution of SI E. amylovora in North America and Europe.

PMID- 29178621
TI  - Macrophages Driving Heterotopic Ossification: Convergence of Genetically-Driven
      and Trauma-Driven Mechanisms.

PMID- 29178622
TI  - Revisiting the functional anatomy of the palmaris longus as a thenar synergist.
AB  - Surgical studies describe the palmaris longus (PL) as a synergist in thumb
      abduction, which may facilitate its use in restoring thumb function using
      opponensplasty. However, beyond morphological descriptions and isometric thenar
      abduction strength measures, the evidence supporting the PL as a thenar synergist
      in-vivo is limited. The purpose here was to determine whether the PL provides
      synergistic contributions to thenar musculature by: (1) recording PL muscle
      activity using indwelling electromyography (EMG) during thumb movements; and (2)
      quantifying changes in PL muscle architecture using ultrasonography. In 10
      healthy males, PL muscle activity was recorded during maximal thenar muscle
      contractions (abduction, flexion, opposition, adduction, and extension) with the
      wrist secured in a neutral position. The PL EMG was normalized to its maximal EMG
      recorded during isometric wrist flexion. Dynamic changes in PL muscle thickness
      (MT ) were determined during abduction and adduction using ultrasound imaging.
      The results indicate that the PL is activated during thenar movements with
      greatest relative PL EMG recorded during thenar abduction (46%), flexion (35%)
      and opposition (37%). Compared to rest, PL MT significantly increased (21%)
      during maximal thenar abduction. With direct measures in vivo, this study
      supports morphological and surgical observations indicating the PL acts as an
      extrinsic hand muscle in enhancing thenar muscle actions. Knowledge of the
      synergistic relationship between the PL and thenar musculature may allow for
      further development of surgical opponensplasty approaches using the abductor
      pollicis brevis and PL as a functional digastric unit. Clin. Anat. 31:760-770,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29178623
TI  - A Chiral Halogen-Bonding [3]Rotaxane for the Recognition and Sensing of
      Biologically Relevant Dicarboxylate Anions.
AB  - The unprecedented application of a chiral halogen-bonding [3]rotaxane host system
      for the discrimination of stereo- and E/Z geometric isomers of a dicarboxylate
      anion guest is described. Synthesised by a chloride anion templation strategy,
      the [3]rotaxane host recognises dicarboxylates through the formation of 1:1
      stoichiometric sandwich complexes. This process was analysed by molecular
      dynamics simulations, which revealed the critical synergy of halogen and hydrogen
      bonding interactions in anion discrimination. In addition, the centrally located
      chiral (S)-BINOL motif of the [3]rotaxane axle component facilitates the
      complexed dicarboxylate species to be sensed via a fluorescence response.

PMID- 29178624
TI  - Clinical and genetic characteristics of xeroderma pigmentosum in Nepal.
AB  - BACKGROUND: Little is known about xeroderma pigmentosum (XP) in Himalayan
      countries. OBJECTIVE: To describe clinical characteristics of XP in Nepal and
      investigate its genetic bases. METHODS: This study was carried out on all
      consecutive patients referred for XP to a Nepalese tertiary referral centre in
      2014-2015. Clinical data were collected using a standardized questionnaire. DNA
      was extracted from salivary samples, and next-generation sequencing (NGS) was
      conducted using a panel covering all 8 known XP genes (classical XP (XP-A to XP
      G) and XP variant) and a skin cancer modifier gene, the melanocortin 1 receptor
      gene (MC1R). RESULTS: Seventeen patients (median age: 15 years; range: 1-32) were
      included. Twelve had skin cancers (including a total of 8 squamous cell
      carcinomas, 60 basal cell carcinomas, ocular carcinomas requiring an orbital
      exenteration in 3 patients, but no melanoma). Fifteen patients carried the same
      homozygous non-sense XPC mutation c.1243C>T, p.R415X. A homozygous non-sense XPA
      mutation (p.W235X) was found in the only patient with a history of early severe
      sunburn reaction and associated neurological symptoms. Associated genetic
      alterations included heterozygous missense variants in XPD/ERCC2 gene and the
      presence of MC1R variant R163Q in 5 and 9 patients, respectively. CONCLUSION:
      Although not previously reported, XP seems frequent in Nepal. Patients often
      presented with a very severe phenotype after a long history of excessive sun
      exposure without knowledge of the disease. Fifteen of 17 had the same p.R415X XPC
      mutation, which seems very specific of XP in Nepal, suggesting a founder effect.
      NGS analyses frequently revealed associated genetic alterations which could play
      a modifier role in the clinical expression of the disease.

PMID- 29178626
TI  - Supramolecular Chirality Issues in Unorthodox Naphthalene Diimide Gelators.
AB  - Herein, the self-assembly of a few 1,3-dihydroxyl functionalized naphthalene
      diimide (NDI) derivatives has been reported with particular emphasis on the
      impact of chirality on gelation and the effect of self-assembly on charge-carrier
      mobility. A nonconventional gelator (R)-NDI, devoid of any long alkyl chains,
      exhibited spontaneous gelation in tetra-chloroethylene (TCE). Based on X-ray
      crystallography and powder X-ray diffraction studies, it was established that a
      ladder-like hydrogen-bonded chain formation between the 1,3-dihydroxyl group
      leads to the fibrillar structures with preferential helicity. Likewise the (S)
      isomer also exhibited identical gelation and mesoscopic structure but produced
      fibrils with the opposite handedness. Intriguingly, an equimolar mixture of the
      (R)- and (S)-isomers did not show any gelation ability, rather a macroscopic
      precipitation was observed and, in sharp contrast to the individual isomers, the
      morphology of the mixture showed ill-defined near spherical agglomerates.
      Differential scanning calorimetry (DSC) studies revealed an identical
      crystallization peak for the supramolecular polymer produced from the enantiopure
      gelators ((R)- or (S)-isomer), which was absent in their equimolar mixture.
      However, mixtures of the two isomers with enantiomeric excess retrieved the
      gelation ability and preferential helicity demonstrating that chiral
      amplification is operative in the present system through the so-called "majority
      rule" effect. Chirality induction was also realized by the "sergeant and soldier"
      principle in the supramolecular assembly of an achiral NDI gelator in the
      presence of either the (R)- or (S)-isomer as the chiral dopant. However, the
      strong helical bias induced by the chiral gelator was found to be opposite in
      nature compared to that found in the self-assembly of the pure chiral gelator
      that has been rarely reported in the literature. Flash-photolysis time-resolved
      microwave conductivity (FP-TRMC) measurements indicated the strong positive
      impact of the gelation on the electrical conductivity.

PMID- 29178625
TI  - Ileus Management International (IMAGINE): protocol for a multicentre,
      observational study of ileus after colorectal surgery.
AB  - AIM: The management of postoperative ileus following colorectal surgery remains
      controversial. It is the commonest complication after elective colorectal
      resection and is associated with an increased incidence of postoperative adverse
      events. The prevention and management of postoperative ileus remains
      unstandardized. This study aims to describe an international profile of
      gastrointestinal recovery after colorectal surgery and will assess the role of
      non-steroidal anti-inflammatory drugs, when used as postoperative analgesia, in
      expediting the return of gastrointestinal function. METHODS: A multicentre,
      student- and trainee-led, prospective cohort study will be conducted across both
      Europe and Australasia. Adult patients undergoing elective colorectal resection
      during 2-week data collection periods between January and April 2018 will be
      included. A site-specific questionnaire will capture compliance to Enhanced
      Recovery after Surgery components at participating centres. The primary outcome
      is time to gastrointestinal recovery, measured using a composite outcome of bowel
      function and oral tolerance. The impact of non-steroidal anti-inflammatory drugs
      on gastrointestinal recovery will be evaluated along with safety data with
      respect to anastomotic leak, acute kidney injury and complications within 30 days
      of surgery. DISCUSSION: This protocol describes the methodology of an
      international, observational assessment of gastrointestinal recovery after
      colorectal surgery. It discusses key challenges and describes how the results
      will impact on future investigation. The study will be conducted across a large
      student- and trainee-led collaborative network, with prospective quality
      assurance and data validation strategies.

PMID- 29178627
TI  - Cell extracts from spleen and adipose tissues restore function to irradiation
      injured salivary glands.
AB  - A cell extract from whole bone marrow (BM), which we named "BM Soup," has the
      property to restore saliva secretion to irradiation (IR)-injured salivary glands
      (SGs). However, BM cell harvesting remains an invasive procedure for the donor.
      The main objective of this study was to test the therapeutic effect of "Cell
      Soups" obtained from alternate tissues, such as adipose-derived stromal cells
      (ADSCs) and spleen cells to repair SGs. BM Soup, Spleen Soup, ADSC Soup, or
      saline (vehicle control) was injected intravenously into mice with IR-injured SGs
      (13Gy). Results demonstrated that all three cell soups restored 65-70% of saliva
      secretion, protected acinar cells, blood vessels, and parasympathetic nerves, and
      increased cell proliferation. Although protein array assays identified more
      angiogenesis-related growth factors in ADSC Soup, the length of its therapeutic
      efficiency on saliva flow was less than that of the BM Soup and Spleen Soup.
      Another objective of this study was to compare "Fresh" versus "Cryopreserved (-80
      degrees C)" BM Soup. It was found that the therapeutic effect of 12-month
      "Cryopreserved BM Soup" was comparable to that of "Fresh BM Soup" on the
      functional restoration of IR-injured SGs. In conclusion, both Spleen Soup and
      ADSC Soup can be used to mitigate IR-damaged SGs.

PMID- 29178628
TI  - Jk3 antibodies complicated with severe fetal anaemia requiring intrauterine
      transfusion: a case report.

PMID- 29178629
TI  - Analysis of emerging organic contaminants in poultry manure by gas chromatography
      tandem mass spectrometry.
AB  - A multiresidue method was developed for the determination of 19 emerging organic
      contaminants (pharmaceutical drugs, personal care products, and bisphenol A) in
      poultry manure. Lyophilized samples of manure were extracted by ultrasound
      assisted matrix solid-phase dispersion and the extracts were analyzed by gas
      chromatography with tandem mass spectrometry after derivatization. Analysis of
      spiked poultry manure samples, at levels ranging from 25 to 150 ng/g, gave
      satisfactory recovery results for all the compounds, with values from 67 to 106%.
      The developed procedure provided detection limits that ranged from 0.9 to 2.2
      ng/g. Finally, the validated method was applied to poultry manure samples
      collected from 23 poultry farms in Spain. Salicylic acid was found in most of the
      samples analyzed at levels up to 2501 ng/g, whereas, methyl paraben,
      orthophenylphenol, ibuprofen, paracetamol, and carbamazepine were detected at
      levels up to 250 ng/g. Composting of manure showed an important decrease in the
      levels of the detected contaminants.

PMID- 29178630
TI  - Clinical settings in a preliminary study: Noninvasive high-frequency oscillatory
      ventilation versus nasal continuous positive airway pressure in preterm infants
      with moderate-severe respiratory distress syndrome.

PMID- 29178631
TI  - Cardioprotection gain with apelin-13: A matter of signalling.

PMID- 29178632
TI  - Different prostaglandin F2 alpha secretion in response to oxytocin injection
      between pregnant and non-pregnant cows: effect of the day of oxytocin challenge
      test for determining the difference.
AB  - The present study was conducted to determine the difference in plasma
      prostaglandin F2 alpha metabolite concentrations following oxytocin (OT)
      challenge between pregnant and non-pregnant cows. Experiment 1: cows were
      subjected to the OT challenge test on days 12, 14 or 16 (day of estrus = day 0)
      with or without prior insemination and plasma 13,14-dihydro-15-keto prostaglandin
      F2 alpha (PGFM) concentrations were measured from -30 to 180 min after OT
      injection. On day 16, the increment of plasma PGFM concentrations in response to
      OT injection was significantly smaller in pregnant than that in cyclic cows. On
      days 12 and 14, there was little OT-induced PGFM secretion and no difference in
      PGFM increase between the pregnant and cyclic cows. Experiment 2: cows were
      inseminated on day 0 and subjected to the OT challenge test on day 16. Cows were
      classified into non-pregnant/early embryonic death (NP/EED), late embryonic death
      (LED) and pregnant (PREG) groups. The increment of PGFM concentrations in
      response to OT injection was less in both PREG and LED groups than that in the
      NP/EED group. In conclusion, plasma PGFM secretion induced by OT is suggested as
      the base of pregnancy diagnosis prior to returning estrus in cows.

PMID- 29178634
TI  - Two Distinct Substrate Binding Modes for the Normal and Reverse Prenylation of
      Hapalindoles by the Prenyltransferase AmbP3.
AB  - The cyanobacterial prenyltransferase AmbP3 catalyzes the reverse prenylation of
      the tetracyclic indole alkaloid hapalindole U at its C-2 position. Interestingly,
      AmbP3 also accepts hapalindole A, a halogenated C-10 epimer of hapalindole U, and
      catalyzes normal prenylation at its C-2 position. The comparison of the two
      ternary crystal structures, AmbP3-DMSPP/hapalindole U and AmbP3-DMSPP/hapalindole
      A, at 1.65-2.00 A resolution revealed two distinct orientations for the substrate
      binding that define reverse or normal prenylation. The tolerance of the enzyme
      for these altered orientations is attributed to the hydrophobicity of the
      substrate binding pocket and the plasticity of the amino acids surrounding the
      allyl group of the prenyl donor. This is the first study to provide the intimate
      structural basis for the normal and reverse prenylations catalyzed by a single
      enzyme, and it offers novel insight into the engineered biosynthesis of
      prenylated natural products.

PMID- 29178633
TI  - Norfloxacin salts of carboxylic acids curtail planktonic and biofilm mode of
      growth in ESKAPE pathogens.
AB  - AIMS: To enhance the antimicrobial and antibiofilm activity of norfloxacin
      against the planktonic and biofilm mode of growth in ESKAPE pathogens using
      chemically modified norfloxacin salts. METHODS AND RESULTS: Antimicrobial
      testing, synergy testing and time-kill curve analysis were performed to evaluate
      antibacterial effect of norfloxacin carboxylic acid salts against ESKAPE
      pathogens. In vivo efficacy to reduce bacterial bioburden was evaluated in
      zebrafish infection model. Crystal violet assay and live-dead staining were
      performed to discern antibiofilm effect. Membrane permeability, integrity and
      molecular docking studies were carried out to ascertain the mechanism of action.
      The carboxylic acid salts, relative to parent molecule norfloxacin, displayed two
      to fourfold reduction in minimum inhibitory concentration against Staphylococcus
      aureus and Pseudomonas aeruginosa, in addition to displaying potent
      bacteriostatic effect against certain members of ESKAPE pathogens. In vivo
      treatments revealed that norfloxacin tartrate (SRIN2) reduced MRSA bioburden by
      greater than 1 log fold relative to parent molecule in the muscle tissue. In
      silico docking with gyrA of S. aureus showed increased affinity of SRIN2 towards
      DNA gyrase. The enhanced antibacterial effect of norfloxacin salts could be
      partially accounted by altered membrane permeability in S. aureus and perturbed
      membrane integrity in P. aeruginosa. Antibiofilm studies revealed that SRIN2
      (norfloxacin tartrate) and SRIN3 (norfloxacin benzoate) exerted potent
      antibiofilm effect particularly against Gram-negative ESKAPE pathogens. The
      impaired colonization of both S. aureus and P. aeruginosa due to improved
      norfloxacin salts was further supported by live-dead imaging. CONCLUSION:
      Norfloxacin carboxylic acid salts can act as potential alternatives in terms of
      drug resensitization and reuse. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study
      shows that carboxylic acid salts of norfloxacin could be effectively employed to
      treat both planktonic- and biofilm-based infections caused by select members of
      ESKAPE pathogens.

PMID- 29178635
TI  - Effect of non-surgical weight management on weight and glycaemic control in
      people with type 2 diabetes: A comparison of interventional and non
      interventional outcomes at 3 years.
AB  - AIMS: To examine the long-term effectiveness of lifestyle weight management
      interventions, recommended in clinical guidelines for patients with type 2
      diabetes mellitus (T2DM) and obesity. MATERIALS AND METHODS: Electronic health
      records were used to follow 23 208 patients with T2DM and obesity in Glasgow, UK,
      for up to 3 years between 2005 and 2014. Patients were stratified by referral to
      and attendance at a lifestyle weight management intervention, and by attainment
      of a target weight loss of >=5 kg over 7 to 9 sessions ("successful completers").
      Outcomes were change in weight, glycated haemoglobin (HbA1c) and diabetes
      medications. RESULTS: A total of 3471 potentially eligible patients were referred
      to the service, and fewer than half of these attended (n = 1537). Of those who
      attended 7 to 9 sessions, >40% successfully completed and achieved 5-kg weight
      loss (334/808). Successful completers maintained greater weight loss (change at 3
      years -8.03 kg; 95% confidence interval [CI] -9.44 to -6.62) than the non
      completers (-3.26 kg; 95% CI -4.01 to -2.51; P < .001) and those not referred to
      the service (-1.00 kg; 95% CI -1.15 to -0.85; P < .001). Successful completers
      were the only patient group who did not increase their use of diabetes medication
      and insulin over 3 years. In adjusted models, successful completers had a
      clinically significant reduction in HbA1c (-3.7 mmol/mol; 95% CI -5.82 to -1.51)
      after 3 years; P <= .001) compared with non-completers and unsuccessful
      completers. CONCLUSIONS: A real-life structured weight management intervention in
      patients with diabetes can reduce weight in the medium term, result in improved
      glycaemic control with fewer medications, and may be more effective than
      pharmacological alternatives. Challenges include getting a higher proportion of
      patients referred to and engaged with interventions.

PMID- 29178636
TI  - A novel splice site variant in CYP11A1 in trans with the p.E314K variant in a
      male patient with congenital adrenal insufficiency.
AB  - BACKGROUND: The CYP11A1 gene encodes the cytochrome P450 side-chain cleavage
      enzyme, which is essential for steroid formation. Recessive variants in this gene
      can lead to impairment of sexual differentiation caused by a complete or partial
      loss of steroid hormone production. The phenotypic spectrum in affected 46XY
      males may vary from surgically repairable defects including cryptorchidism and
      hypospadias to complete feminization of external gonads, accompanied by symptoms
      of adrenal dysfunction. METHODS: Whole-exome sequencing (WES) of a 12-year-old
      male proband and his parents was performed after a protracted diagnostic odyssey
      failed to uncover the cause of his primary adrenal insufficiency. Of note, the
      proband had early symptomatology and corrective surgery for hypospadias, raising
      suspicion for a disorder of steroidogenesis. RESULTS: WES identified compound
      heterozygous variants in CYP11A1 including a novel canonical splice site variant
      (c.425+1G>A) and a previously reported p.E314K variant, which were consistent
      with a diagnosis of congenital adrenal insufficiency with partial 46XY sex
      reversal. CONCLUSION: Congenital adrenal insufficiency with 46XY sex reversal is
      a rare disorder that is characterized by dysregulation of steroid hormone
      synthesis, leading to adrenal and gonadal dysfunction. In this report, we
      describe a patient with adrenal insufficiency, hypospadias, and skin
      hyperpigmentation who was found to have a novel c.425+1G>A variant in trans with
      the p.E314K variant in CYP11A1. We performed structural analyses to examine the
      effect of the p.E314K variant on protein function and show that it falls in the
      core of the protein may disrupt cholesterol binding in the active site.

PMID- 29178637
TI  - Allelic spectrum of formiminotransferase-cyclodeaminase gene variants in
      individuals with formiminoglutamic aciduria.
AB  - BACKGROUND: Elevated plasma and urine formiminoglutamic acid (FIGLU) levels are
      commonly indicative of formiminoglutamic aciduria (OMIM #229100), a poorly
      understood autosomal recessive disorder of histidine and folate metabolism,
      resulting from formiminotransferase-cyclodeaminase (FTCD) deficiency, a
      bifunctional enzyme encoded by FTCD. METHODS: In order to further understanding
      about the molecular alterations that contribute to FIGLU-uria, we sequenced FTCD
      in 20 individuals with putative FTCD deficiency and varying laboratory findings,
      including increased FIGLU excretion. RESULTS: Individuals tested had biallelic
      loss-of-function variants in protein-coding regions of FTCD. The FTCD allelic
      spectrum comprised of 12 distinct variants including 5 missense alterations that
      replace conserved amino acid residues (c.223A>C, c.266A>G, c.319T>C, c.430G>A,
      c.514G>T), an in-frame deletion (c.1373_1375delTGG), with the remaining
      alterations predicted to affect mRNA processing/stability. These included two
      frameshift variants (c.990dup, c.1366dup) and four nonsense variants (c.337C>T,
      c.451A>T, c.763C>T, c.1607T>A). CONCLUSION: We observed additional FTCD alleles
      leading to urinary FIGLU elevations, and thus, providing molecular evidence of
      FTCD deficiency in cases identified by newborn screening or clinical biochemical
      genetic laboratory testing.

PMID- 29178638
TI  - Living with a rare disorder: a systematic review of the qualitative literature.
AB  - BACKGROUND: Individuals with rare diseases may face challenges that are different
      from those experienced in more common medical conditions. A wide range of
      different rare conditions has resulted in a myriad of studies investigating the
      specificities of the diagnosis in focus. The shared psychological experiences of
      individuals with a rare condition, however, have not been reviewed
      systematically. METHODS: We performed a systematic review, including qualitative
      studies on adults, published between 2000 and 2016. Papers including more than
      one rare genetic or nongenetic diagnosis were included. Studies based on single
      diagnoses were excluded except for four specific conditions: hemophilia (bleeding
      disorder), phenylketonuria (metabolic disorder), Fabry disease (lysosomal storage
      disorder), and epidermolysis bullosa (skin disorder). RESULTS: The review
      identified 21 studies. Findings were synthesized and categorized according to
      three main themes: (1) Consequences of living with a rare disorder, (2) Social
      aspects of living with a rare disorder, and (3) Experiences with the health care
      system. Findings point to several unique challenges, such as the psychological,
      medical, and social consequences of a lack of knowledge about the condition in
      health care and social settings. CONCLUSION: The findings highlight the need for
      more research on the shared psychological and social impact of living with a rare
      diagnosis across conditions, in order to identify risk factors and inform
      clinical practice.

PMID- 29178639
TI  - Spectrum of CFTR gene mutations in Ecuadorian cystic fibrosis patients: the
      second report of the p.H609R mutation.
AB  - BACKGROUND: High heterogeneity in the CFTR gene mutations disturbs the molecular
      diagnosis of cystic fibrosis (CF). In order to improve the diagnosis of CF in our
      country, the present study aims to define a panel of common CFTR gene mutations
      by sequencing 27 exons of the gene in Ecuadorian Cystic Fibrosis patients.
      METHODS: Forty-eight Ecuadorian individuals with suspected/confirmed CF diagnosis
      were included. Twenty-seven exons of CFTR gene were sequenced to find sequence
      variations. Prevalence of pathogenic variations were determined and compared with
      other countries' data. RESULTS: We found 70 sequence variations. Eight of these
      are CF-causing mutations: p.F508del, p.G85E, p.G330E, p.A455E, p.G970S, W1098X,
      R1162X, and N1303K. Also this study is the second report of p.H609R in Ecuadorian
      population. Mutation prevalence differences between Ecuadorian population and
      other Latin America countries were found. CONCLUSION: The panel of mutations
      suggested as an initial screening for the Ecuadorian population with cystic
      fibrosis should contain the mutations: p.F508del, p.G85E, p.G330E, p.A455E,
      p.G970S, W1098X, R1162X, and N1303K.

PMID- 29178640
TI  - Expanding the mutational spectrum in Johanson-Blizzard syndrome: identification
      of whole exon deletions and duplications in the UBR1 gene by multiplex ligation
      dependent probe amplification analysis.
AB  - BACKGROUND: Johanson-Blizzard syndrome (JBS, MIM #243800) is a very rare
      autosomal recessive disorder characterized by exocrine pancreatic insufficiency,
      nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by
      mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N
      end rule pathway. METHODS: Molecular findings in a total of 65 unrelated patients
      with a clinical diagnosis of JBS who were previously screened for UBR1 mutations
      by Sanger sequencing were reviewed and cases lacking a disease-causing UBR1
      mutation on either one or both alleles were included in this study. In order to
      discover mutations that are not detectable by Sanger sequencing, we designed a
      probe set for multiplex ligation-dependent probe amplification (MLPA) analysis of
      the UBR1 gene and analyzed the copy number status of all 47 UBR1 exons. RESULTS:
      Our previous studies using Sanger sequencing could detect mutations in 93.1% of
      130 disease-associated UBR1 alleles. Six patients with a highly suggestive
      clinical diagnosis of JBS and unsolved genotype were included in this study. MLPA
      analysis detected six alleles harboring exon deletions/duplications, thereby
      raising the mutation detection rate in the entire cohort to 97.7% (127/130
      alleles). CONCLUSION: We conclude that single or multi-exon deletions or
      duplications account for a substantial proportion of JBS-associated UBR1
      mutations.

PMID- 29178641
TI  - Pediatric healthcare costs for patients with 22q11.2 deletion syndrome.
AB  - BACKGROUND: The 22q11.2 deletion syndrome is a variably expressed disorder that
      can include cardiac, palate, and other physical abnormalities, immunodeficiency,
      and hypocalcemia. Because of the extreme variability in phenotype, there has been
      no available estimate of the total medical expenditure associated with the
      average case. METHODS: We have developed a model to estimate the cost from the
      time of diagnosis to age 20. Costs were based on patients seen at a specialty
      center but also considered those components of care expected to have been
      provided by external healthcare facilities. Expense was based on billed medical
      charges extracted from the electronic medical billing system for all patients
      with a diagnosis of DiGeorge or velocardiofacial syndrome from 1993-2015.
      Expenditures included maternal prenatal care directly related to an affected
      pregnancy, molecular/cytogenetic diagnosis, consultations, surgery, and/or other
      treatment and management. Most mental health services (except inpatient), therapy
      related to cognitive, behavioral, speech, pharmacy, and nonmedical costs (special
      education, vocational, respite, lost earnings) were not included. RESULTS: Data
      were available for 642 patients with 50.7% diagnosed prenatally or in the first
      year of life. The average cost for a patient was $727,178. Costs were highest for
      patients ascertained prenatally ($2,599,955) or in the first year of life
      ($1,043,096), those with cardiac abnormalities or referred for cardiac evaluation
      ($751,535), and patients with low T-cell counts ($1,382,222). CONCLUSION: This
      study demonstrates that there are significant medical costs associated with
      22q11.2 deletion syndrome.

PMID- 29178642
TI  - The genetic profile of Leber congenital amaurosis in an Australian cohort.
AB  - BACKGROUND: Leber congenital amaurosis (LCA) is a severe visual impairment
      responsible for infantile blindness, representing ~5% of all inherited retinal
      dystrophies. LCA encompasses a group of heterogeneous disorders, with 24 genes
      currently implicated in pathogenesis. Such clinical and genetic heterogeneity
      poses great challenges for treatment, with personalized therapies anticipated to
      be the best treatment candidates. Unraveling the individual genetic etiology of
      disease is a prerequisite for personalized therapies, and could identify
      potential treatment candidates, inform patient management, and discriminate
      syndromic forms of disease. METHODS: We have genetically analyzed 45 affected and
      82 unaffected individuals from 34 unrelated LCA pedigrees using predominantly
      next-generation sequencing and Array CGH technology. RESULTS: We present the
      molecular findings for an Australian LCA cohort, sourced from the Australian
      Inherited Retinal Disease Registry & DNA Bank. CEP290 and GUCY2D mutations, each
      represent 19% of unrelated LCA cases, followed by NMNAT1 (12%). Genetic subtypes
      were consistent with other reports, and were resolved in 90% of this cohort.
      CONCLUSION: The high resolution rate achieved, equivalent to recent findings
      using whole exome/genome sequencing, reflects the progression from hypothesis
      (LCA Panel) to non-hypothesis (RD Panel) testing and, coupled with Array CGH
      analysis, is a highly effective first-tier test for LCA.

PMID- 29178644
TI  - Medical genetics and genomic medicine in the United States. Part 2: Reproductive
      genetics, newborn screening, genetic counseling, training, and registries.
AB  - Review of genetics in the United States with emphasis on the prenatal, metabolic,
      genetic counseling, and training aspects of the field.

PMID- 29178643
TI  - Role of WNT10A in failure of tooth development in humans and zebrafish.
AB  - BACKGROUND: Oligodontia is a severe form of tooth agenesis characterized by the
      absence of six or more permanent teeth. Oligodontia has complex etiology and
      variations in numerous genes have been suggested as causal for the condition.
      METHODS: We applied whole-exome sequencing (WES) to identify the cause of
      oligodontia in a 9-year-old girl missing 11 permanent teeth. Protein modeling and
      functional analysis in zebrafish were also performed to understand the impact of
      identified variants on the phenotype. RESULTS: We identified a novel compound
      heterozygous missense mutation in WNT10A (c.637G>A:p.Gly213Ser and
      c.1070C>T:p.Thr357Ile) as the likely cause of autosomal recessive oligodontia in
      the child. Affected residues are located in conserved regions and variants are
      predicted to be highly deleterious for potentially destabilizing the protein fold
      and inhibiting normal protein function. Functional studies in zebrafish embryos
      showed that wnt10a is expressed in the craniofacies at critical time points for
      tooth development, and that perturbations of wnt10a expression impaired normal
      tooth development and arrested tooth development at 5 days postfertilization
      (dpf). Furthermore, mRNA expression levels of additional tooth development genes
      were directly correlated with wnt10a expression; expression of msx1, dlx2b, eda,
      and axin2 was decreased upon wnt10a knockdown, and increased upon wnt10a
      overexpression. CONCLUSIONS: Our results reveal a novel compound heterozygous
      variant in WNT10A as pathogenic for oligodontia, and demonstrate that
      perturbations of wnt10a expression in zebrafish may directly and/or indirectly
      affect tooth development recapitulating the agenesis phenotype observed in
      humans.

PMID- 29178645
TI  - Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target
      in dyskeratosis congenita.
AB  - BACKGROUND: The inherited bone marrow failure syndrome dyskeratosis congenita
      (DC) is most frequently caused by mutations in DKC1 (MIM# 300126), the gene
      encoding NAP57 (aka dyskerin). The typically missense mutations modulate the
      interaction of NAP57 with its chaperone SHQ1, but no DC mutations have been
      identified in SHQ1 (MIM# 613663). Here, we report on two compound heterozygous
      mutations in SHQ1 in a patient with a severe neurological disorder including
      cerebellar degeneration. METHODS: The SHQ1 mutations were identified by patient
      exome sequencing. The impact of the mutations was assessed in pulldown assays
      with recombinant NAP57. RESULTS: The SHQ1 mutations were the only set of
      mutations consistent with an autosomal recessive mode of inheritance. The
      mutations map to the SHQ1-NAP57 interface and impair the interaction of the
      recombinant SHQ1 variants with NAP57. CONCLUSION: Intrauterine growth retardation
      and the neurological phenotype of the patient are reminiscent of the severe
      clinical variant of DC, the Hoyeraal-Hreidarsson syndrome (HH). Hence, SHQ1
      screening may be warranted in patients with inherited bone marrow failure
      syndromes.

PMID- 29178646
TI  - Novel autosomal dominant TNNT1 mutation causing nemaline myopathy.
AB  - BACKGROUND: Nemaline myopathy (NEM) is one of the three major forms of congenital
      myopathy and is characterized by diffuse muscle weakness, hypotonia, respiratory
      insufficiency, and the presence of nemaline rod structures on muscle biopsy.
      Mutations in troponin T1 (TNNT1) is 1 of 10 genes known to cause NEM. To date,
      only homozygous nonsense mutations or compound heterozygous truncating or
      internal deletion mutations in TNNT1 gene have been identified in NEM. This
      extended family is of historical importance as some members were reported in the
      1960s as initial evidence that NEM is a hereditary disorder. METHODS: Proband and
      extended family underwent Sanger sequencing for TNNT1. We performed RT-PCR and
      immunoblot on muscle to assess TNNT1 RNA expression and protein levels in proband
      and father. RESULTS: We report a novel heterozygous missense mutation of TNNT1
      c.311A>T (p.E104V) that segregated in an autosomal dominant fashion in a large
      family residing in the United States. Extensive sequencing of the other known
      genes for NEM failed to identify any other mutant alleles. Muscle biopsies
      revealed a characteristic pattern of nemaline rods and severe myofiber hypotrophy
      that was almost entirely restricted to the type 1 fiber population. CONCLUSION:
      This novel mutation alters a residue that is highly conserved among vertebrates.
      This report highlights not only a family with autosomal dominant inheritance of
      NEM, but that this novel mutation likely acts via a dominant negative mechanism.

PMID- 29178647
TI  - Comprehensive analysis of mutations in the MEFV gene reveal that the location and
      not the substitution type determines symptom severity in FMF.
AB  - BACKGROUND: Familial Mediterranean Fever (FMF) is an autoinflammatory disorder
      caused by mutations in the MEFV gene. These mutations appear in different
      populations with different frequencies and their caused symptom severities vary
      from mild to moderate to severe depending on the mutation type. METHODS: In this
      study, we analyzed the mutations that have been reported in the MEFV gene from
      symptomatic FMF patients and compared their frequencies in different populations
      from the 1000 Genome and the Exome databases, using statistical clustering. We
      also analyzed the nucleotide and amino acid substitution patterns across the MEFV
      gene. RESULTS: We found 16 (8%) nonsynonymous mutations outside exon 10 that did
      not cluster with known disease-causing mutations (DCMs), due to their high
      frequencies in other populations. We also studied the substitution patterns for
      nucleotides and amino acids to determine the conserved and variable regions in
      the MEFV gene. In general more nonsynonymous substitutions were reported in exons
      2, 3, and 10 from the FMF database (symptomatic FMF patients) compared to the
      1000 Genome and the Exome databases. The same was true for amino acid (AA)
      substitutions where there were 1.5 times more radical (RAD) to conservative (CON)
      changes. However, when it came to AA substitutions exon 10 was quite conserved
      with a RAD/CON ratio of 0.9. In fact, we report that the most severe FMF symptoms
      are caused by conservative mutations in two highly conserved exon 10 regions.
      CONCLUSION: We found presumptive FMF-causing mutations that did not cluster with
      DCMs based on their allele frequencies. We also observed that the type of
      mutation is less likely to determine the severity of the FMF symptoms; rather it
      was the location of the mutations that was the determining factor.

PMID- 29178648
TI  - Panel-based whole exome sequencing identifies novel mutations in microphthalmia
      and anophthalmia patients showing complex Mendelian inheritance patterns.
AB  - BACKGROUND: Microphthalmia and anophthalmia (MA) are congenital eye abnormalities
      that show an extremely high clinical and genetic complexity. In this study, we
      evaluated the implementation of whole exome sequencing (WES) for the genetic
      analysis of MA patients. This approach was used to investigate three unrelated
      families in which previous single-gene analyses failed to identify the molecular
      cause. METHODS: A total of 47 genes previously associated with nonsyndromic MA
      were included in our panel. WES was performed in one affected patient from each
      family using the AmpliSeqTM Exome technology and the Ion ProtonTM platform.
      RESULTS: A novel heterozygous OTX2 missense mutation was identified in a patient
      showing bilateral anophthalmia who inherited the variant from a parent who was a
      carrier, but showed no sign of the condition. We also describe a new PAX6
      missense variant in an autosomal-dominant pedigree affected by mild bilateral
      microphthalmia showing high intrafamiliar variability, with germline mosaicism
      determined to be the most plausible molecular cause of the disease. Finally, a
      heterozygous missense mutation in RBP4 was found to be responsible in an isolated
      case of bilateral complex microphthalmia. CONCLUSION: This study highlights that
      panel-based WES is a reliable and effective strategy for the genetic diagnosis of
      MA. Furthermore, using this technique, the mutational spectrum of these diseases
      was broadened, with novel variants identified in each of the OTX2, PAX6, and RBP4
      genes. Moreover, we report new cases of reduced penetrance, mosaicism, and
      variable phenotypic expressivity associated with MA, further demonstrating the
      heterogeneity of such disorders.

PMID- 29178650
TI  - Military genomics: a perspective on the successes and challenges of genomic
      medicine in the Armed Services.
AB  - We describe the impact genomics has on the health and readiness of the military
      service member, highlight several examples of the current and future plans for
      genomic medicine within the military, discuss challenges to implementation and
      provide recommendations to address some of those challenges.

PMID- 29178649
TI  - The maternal uniparental disomy of chromosome 6 (upd(6)mat) "phenotype": result
      of placental trisomy 6 mosaicism?
AB  - BACKGROUND: Maternal uniparental disomy of chromosome 6 (upd(6)mat) is a rare
      finding and its clinical relevance is currently unclear. Based on clinical data
      from two new cases and patients from the literature, the pathogenetic
      significance of upd(6)mat is delineated. METHODS: Own cases were molecularly
      characterized for isodisomic uniparental regions on chromosome 6. For further
      cases with upd(6)mat, a literature search was conducted and genetic and clinical
      data were ascertained. RESULTS: Comparison of isodisomic regions between the new
      upd(6)mat cases and those from four reports did not reveal any common isodisomic
      region. Among the patients with available cytogenetic data, five had a normal
      karyotype in lymphocytes, whereas a trisomy 6 (mosaicism) was detected prenatally
      in four cases. A common clinical picture was not obvious in upd(6)mat, but
      intrauterine growth restriction (IUGR) and preterm delivery were frequent.
      CONCLUSION: A common upd(6)mat phenotype is not obvious, but placental
      dysfunction due to trisomy 6 mosaicism probably contributes to IUGR and preterm
      delivery. In fact, other clinical features observed in upd(6)mat patients might
      be caused by homozygosity of recessive mutations or by an undetected trisomy 6
      cell line. Upd(6)mat itself is not associated with clinical features, and can
      rather be regarded as a biomarker. In case upd(6)mat is detected, the cause for
      the phenotype is identified indirectly, but the UPD is not the basic cause.

PMID- 29178651
TI  - Clinical verification of genetic results returned to research participants:
      findings from a Colon Cancer Family Registry.
AB  - BACKGROUND: The extent to which participants act to clinically verify research
      results is largely unknown. This study examined whether participants who received
      Lynch syndrome (LS)-related findings pursued researchers' recommendation to
      clinically verify results with testing performed by a CLIA-certified laboratory.
      METHODS: The Fred Hutchinson Cancer Research Center site of the multinational
      Colon Cancer Family Registry offered non-CLIA individual genetic research results
      to select registry participants (cases and their enrolled relatives) from 2011 to
      2013. Participants who elected to receive results were counseled on the
      importance of verifying results at a CLIA-certified laboratory. Twenty-six
      (76.5%) of the 34 participants who received genetic results completed 2- and 12
      month postdisclosure surveys; 42.3% of these (11/26) participated in a
      semistructured follow-up interview. RESULTS: Within 12 months of result
      disclosure, only 4 (15.4%) of 26 participants reported having verified their
      results in a CLIA-certified laboratory; of these four cases, all research and
      clinical results were concordant. Reasons for pursuing clinical verification
      included acting on the recommendation of the research team and informing future
      clinical care. Those who did not verify results cited lack of insurance coverage
      and limited perceived personal benefit of clinical verification as reasons for
      inaction. CONCLUSION: These findings suggest researchers will need to address
      barriers to seeking clinical verification in order to ensure that the intended
      benefits of returning genetic research results are realized.

PMID- 29178652
TI  - Mutations in fetal genes involved in innate immunity and host defense against
      microbes increase risk of preterm premature rupture of membranes (PPROM).
AB  - BACKGROUND: Twin studies have revealed a significant contribution of the fetal
      genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM)
      is the leading identifiable cause of preterm delivery. Infection and inflammation
      of the fetal membranes is commonly found associated with PPROM. METHODS: We
      carried out whole exome sequencing (WES) of genomic DNA from neonates born of
      African-American mothers whose pregnancies were complicated by PPROM (76) or were
      normal term pregnancies (N = 43) to identify mutations in 35 candidate genes
      involved in innate immunity and host defenses against microbes. Targeted
      genotyping of mutations in the candidates discovered by WES was conducted on an
      additional 188 PPROM cases and 175 controls. RESULTS: We identified rare
      heterozygous nonsense and frameshift mutations in several of the candidate genes,
      including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered
      that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in
      PPROM cases. CONCLUSIONS: We conclude that rare damaging mutations in innate
      immunity and host defense genes, the majority being heterozygous, are more
      frequent in neonates born of pregnancies complicated by PPROM. These findings
      suggest that the risk of preterm birth in African-Americans may be conferred by
      mutations in multiple genes encoding proteins involved in dampening the innate
      immune response or protecting the host against microbial infection and microbial
      products.

PMID- 29178653
TI  - Compound heterozygous CASQ2 mutations and long-term course of catecholaminergic
      polymorphic ventricular tachycardia.
AB  - BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a
      potentially lethal inherited cardiac disorder characterized by episodic
      ventricular tachycardia during adrenergic stimulation. It is associated with
      significant morbidity and mortality. Knowledge of the underlying genetic cause,
      pathogenesis, and the natural history of the disease remains incomplete.
      Approximately 50% of CPVT cases are caused by dominant mutations in the cardiac
      ryanodine receptor (RYR2) gene, <5% of cases are accounted for by recessive
      mutations in cardiac calsequestrin (CASQ2) or Triadin (TRDN). METHODS: We report
      a family with two CASQ2 gene mutations. A research-based next-generation
      sequencing (NGS) initiative was used in a patient with a severe CPVT phenotype
      and her clinically unaffected son. Reverse transcription polymerase chain
      reaction (RT-PCR) from platelet RNA was used to assess the consequences of
      predicted splice variants. RESULTS: NGS revealed that the proband carried a novel
      c.199C>T (p.Gln67*) mutation and a previously reported splice site mutation
      c.532+1G>A in CASQ2. Her son is a heterozygous carrier of the c.199C>T (p.Gln67*)
      mutation alone and the proband was compound heterozygous at CASQ2. RNA analysis
      demonstrated that the splice site mutation results in the retention of intron 3
      with no full-length CASQ2 mRNA. CONCLUSION: This study describes a novel CPVT
      genotype and further characterizes the effect of a previously reported CASQ2
      splice site mutation. The long-term follow-up of 23 years since first symptom
      provides additional insight into the natural history of CASQ2-associated CPVT.

PMID- 29178655
TI  - RYR1 causing distal myopathy.
AB  - BACKGROUND: Congenital myopathies due to ryanodine receptor (RYR1) mutations are
      increasingly identified and correlate with a wide range of phenotypes, most
      commonly that of malignant hyperthermia susceptibility and central cores on
      muscle biopsy with rare reports of distal muscle weakness, but in the setting of
      early onset global weakness. METHODS: We report a case of a patient presenting
      with childhood onset hand stiffness and adult onset progressive hand weakness and
      jaw contractures discovered to have two variants in the RYR1 gene. RESULTS: The
      patient manifested with distal upper limb weakness which progressed to involve
      the distal lower limb, proximal upper limb, as well as the face in addition to
      limited jaw opening. Creatine kinase was mildly elevated with EMG findings
      supporting a myopathy. Muscle biopsy showed features consistent with
      centronuclear myopathy. Whole exome sequencing revealed a novel heterozygous
      pathogenic variant in RYR1 (c.12315_12328delAGAAATCCAGTTCC, p.Glu4106Alafs*8),
      and a heterozygous missense variant (c.10648C>T, p.Arg3550Trp) of unknown
      significance in compound heterozygous state. CONCLUSION: We expand the spectrum
      of RYR1-related myopathy with the description of a novel phenotype in an adult
      patient presenting with hand weakness and suggest considering RYR1 analysis in
      the diagnosis of distal myopathies.

PMID- 29178654
TI  - Sickle cell trait knowledge and health literacy in caregivers who receive in
      person sickle cell trait education.
AB  - BACKGROUND: Despite universal screening that detects sickle cell trait (SCT) in
      infancy, only 16% of Americans with SCT know their status. To increase SCT status
      awareness, effective education for patients and their families is needed. The
      objective of this study was to assess caregivers' SCT knowledge before and after
      an in-person SCT education session. METHODS: A trained educator provides in
      person SCT education to caregivers of referred infants with SCT at Nationwide
      Children's Hospital. From August 2015 to July 2016, primarily English-speaking
      caregivers of infants with hemoglobin S-trait were recruited and completed a
      health literacy assessment and a SCT knowledge assessment (SCTKA) before and
      after receiving education. Caregivers repeated the SCTKA again after >=6 months,
      if they could be contacted. RESULTS: Thirty-eight (38.1%) percent of 113
      caregivers had high SCTKA scores (>=75%) before education but 90.3% achieved high
      scores after education. Caregivers with low SCTKA scores after education had
      significantly lower health literacy (P = 0.029) and baseline SCTKA scores (P =
      0.003) compared to those with higher scores after education. At >=6 months,
      caregivers' scores were significantly higher (P = 0.014) than baseline, but only
      73.3% scored >=75%. CONCLUSION: Our results suggest that caregivers' baseline SCT
      knowledge is low, improves with in-person education but may decline with time.
      Caregivers who do not achieve high SCT knowledge after education had lower health
      literacy and baseline knowledge. Future studies should determine if adapting in
      person education to caregivers' health literacy and knowledge levels results in
      high and sustained SCT knowledge among all caregivers and more individuals who
      know their SCT status.

PMID- 29178657
TI  - Does obesity cause a distinct phenotype of hidradenitis suppurativa?

PMID- 29178656
TI  - Unique genetic background and outcome of non-Caucasian Japanese probands with
      arrhythmogenic right ventricular dysplasia/cardiomyopathy.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is
      an inherited cardiomyopathy mainly caused by desmosomal gene mutation. More than
      half of Caucasian probands have desmosomal mutations, which lead to earlier onset
      of ventricular arrhythmias. Among non-Caucasians, the genetic background of
      ARVD/C probands and its prognostic impact remain unclear. METHODS AND RESULTS: We
      genotyped 99 unrelated Japanese ARVD/C probands for plakophilin 2 (PKP2),
      desmoglein 2 (DSG2), desmoplakin (DSP), and desmocollin 2 (DSC2) between 2005 and
      2014. Seventy-five probands who fulfilled "definite" category according to the
      2010 Task Force Criteria (TFC) were enrolled and followed up for 6.4 years. Sixty
      four percent of probands had desmosomal mutations; DSG2 was predominant (48% of
      mutations) followed by PKP2 (38%). DSG2 mutations were almost missense, whereas
      over 90% of PKP2 mutations were truncating mutations. Lethal ventricular
      arrhythmias (VAs, sustained ventricular tachycardia/fibrillation) occurred in 57%
      of probands as the first manifestation and 71% at the end of follow-up. Five died
      during follow-up. Truncating mutation carriers exhibited earlier lethal VAs onset
      compared to missense mutation carriers or mutation negatives (age at onset 35 +/-
      12, 49 +/- 16, and 50 +/- 19 years, respectively, P < 0.05 in each). Cox
      proportional hazard analysis revealed for the first time that, compared to
      mutation negatives, truncating mutation carriers had higher risk for lethal VAs,
      and especially for onset by their 40s, in an age-dependent manner (RR = 4.6, P <
      0.01 by their 40s; RR = 2.9, P = 0.01 by their 50s). CONCLUSION: The genetic
      background of Japanese ARVD/C probands is distinct from that of Caucasian
      probands, leading to distinct prognosis. The most affected gene mutations in
      Japanese probands were missense mutations in DSG2 leading to modest outcome,
      whereas PKP2 truncating mutations were the second most and might be a strong
      marker for lethal VAs in non-Caucasian Japanese ARVD/C probands.

PMID- 29178658
TI  - High-Pressure-Induced Comminution and Recrystallization of CH3 NH3 PbBr3
      Nanocrystals as Large Thin Nanoplates.
AB  - High pressure (HP) can drive the direct sintering of nanoparticle assemblies for
      Ag/Au, CdSe/PbS nanocrystals (NCs). Instead of direct sintering for the
      conventional nanocrystals, this study experimentally observes for the first time
      high-pressure-induced comminution and recrystallization of organic-inorganic
      hybrid perovskite nanocrystals into highly luminescent nanoplates with a shorter
      carrier lifetime. Such novel pressure response is attributed to the unique
      structural nature of hybrid perovskites under high pressure: during the drastic
      cubic-orthorhombic structural transformation at ~2 GPa, (301) the crystal plane
      fully occupied by organic molecules possesses a higher surface energy, triggering
      the comminution of nanocrystals into nanoslices along such crystal plane. Beyond
      bulk perovskites, in which pressure-induced modifications on crystal structures
      and functional properties will disappear after pressure release, the pressure
      formed variants, i.e., large (~100 nm) and thin (<10 nm) perovskite nanoplates,
      are retained and these exhibit simultaneous photoluminescence emission enhancing
      (a 15-fold enhancement in the photoluminescence) and carrier lifetime shortening
      (from ~18.3 +/- 0.8 to ~7.6 +/- 0.5 ns) after releasing of pressure from 11 GPa.
      This pressure-induced comminution of hybrid perovskite NCs and a subsequent
      amorphization-recrystallization treatment offer the possibilities of engineering
      the advanced hybrid perovskites with specific properties.

PMID- 29178660
TI  - Motion contrast in primary visual cortex: a direct comparison of single neuron
      and population encoding.
AB  - Features from outside the classical receptive field (CRF) can modulate the
      stimulus-driven activity of single cells in the primary visual cortex. This
      modulation, mediated by horizontal and feedback networks, has been extensively
      described as a variation of firing rate and is considered the basis of processing
      features as, for example, motion contrast. However, surround influences have also
      been identified in pairwise spiking or local field coherence. Yet, evidence about
      co-existence and integration of different neural signatures remains elusive. To
      compare multiple signatures, we recorded spiking and LFP activity evoked by
      stimuli exhibiting a motion contrast in the CRFs surround in anesthetized cat
      primary visual cortex. We chose natural-like scenes over gratings to avoid
      predominance of simple visual features, which could be easily represented by a
      rate code. We analyzed firing rates and phase-locking to low-gamma frequency in
      single cells and neuronal assemblies. Motion contrast was reflected in all
      measures but in semi-independent populations. Whereas activation of assemblies
      accompanied single neuron rates, their phase relations were modulated
      differently. Interestingly, only assembly phase relations mirrored the direction
      of movement of the surround and were selectively affected by thermal deactivation
      of visual interhemispheric connections. We argue that motion contrast can be
      reflected in complementary and superimposed neuronal signatures that can
      represent different surround features in independent neuronal populations.

PMID- 29178659
TI  - Behavioral Weight Loss Intervention for Migraine: A Randomized Controlled Trial.
AB  - OBJECTIVE: The objective of this study was to test whether behavioral weight loss
      (BWL) intervention decreases headaches in women with comorbid migraine and
      overweight or obesity. METHODS: This randomized, single-blind trial allocated
      women 18 to 50 years old with 4 to 20 migraine days per month and a BMI = 25.0
      49.9 kg/m2 to 16 weeks of BWL (n = 54), which targeted exercise and eating
      behaviors for weight loss, or to migraine education control (ME, n = 56), which
      delivered didactic instruction on migraine and treatments. Participants completed
      a 4-week smartphone headache diary at baseline, posttreatment (16-20 wk), and
      follow-up (32-36 wk). The primary outcome was posttreatment change in migraine
      days per month, analyzed via linear mixed effects models. RESULTS: Of 110
      participants randomly assigned, 85 (78%) and 80 (73%) completed posttreatment and
      follow-up. Although the BWL group achieved greater weight loss (mean [95% CI] in
      kilograms) than the ME group at posttreatment (-3.8 [-2.5 to -5.0] vs. + 0.9 [
      0.4 to 2.2], P < 0.001) and follow-up (-3.2 [-2.0 to -4.5] vs. + 1.1 [-0.2 to
      2.4], P < 0.001), there were no significant group (BWL vs. ME) differences (mean
      [95% CI]) in migraine days per month at posttreatment (-3.0 [-2.0 to -4.0] vs. 
      4.0 [-2.9 to -5.0], P = 0.185) or follow-up (-3.8 [-2.7 to -4.8] vs. -4.4 [-3.4
      to -5.5], P = 0.378). CONCLUSIONS: Contrary to hypotheses, BWL and ME yielded
      similar, sustained reductions in migraine headaches. Future research should
      evaluate whether adding BWL to standard pharmacological and/or nonpharmacological
      migraine treatment approaches yields greater benefits.

PMID- 29178661
TI  - Quantification of classical HLA class I mRNA by allele-specific, real-time
      polymerase chain reaction for most Han individuals.
AB  - Recent studies have shown that expression levels of different alleles at the same
      HLA class I locus can vary dramatically, which might have a broad influence on
      human disease. However, precise quantification of the relative expression level
      of each HLA allele is challenging, because distinguishing different alleles on
      the same locus is difficult. Here, we developed a series of allele-specific, real
      time polymerase chain reaction assays for quantifying HLA class I allele mRNA in
      most Han individuals. The alleles of almost all heterozygous genotypes with a
      frequency higher than 0.5% in our population (78 alleles on HLA-A locus, 124
      alleles on HLA-B locus, and 74 alleles on HLA-C locus) were specifically
      amplified. The specificity of the amplification was strictly validated by setting
      the corresponding negative control for each allele of each genotype. The
      amplification efficiency of each reaction was determined, and the slopes of the
      reactions were compared. This study provides a tool for detecting the
      comprehensive expression profile of HLA class I alleles and will be useful not
      only for the investigation of the molecular mechanism underlying HLA allele
      expression regulation but also for exploration of immunological mechanisms
      involving HLA expression in the fields of tumour immune evasion, viral infection,
      auto-immune disorders, and graft vs host disease after haematopoietic stem cell
      transplantation.

PMID- 29178662
TI  - Addiction research centres and the nurturing of creativity: The Centre for
      Alcohol Policy Research (CAPR), Melbourne: a decade on.
AB  - Established in 2006, the Centre for Alcohol Policy Research (CAPR) is Australia's
      only research centre with a primary focus on alcohol policy. CAPR has four main
      areas of research: alcohol policy impacts; alcohol policy formation and
      regulatory processes involved in implementing alcohol policies; patterns and
      trends in drinking and alcohol problems in the population; and the influence of
      drinking norms, cultural practices and social contexts, particularly in
      interaction with alcohol policies. In this paper, we give examples of key
      publications in each area. During the past decade, the number of staff employed
      at CAPR has increased steadily and now hovers at approximately 10. CAPR has
      supported the development of independent researchers who collaborate on a number
      of international projects, such as the Alcohol's Harm to Others study which is
      now replicated in approximately 30 countries. CAPR receives core funding from the
      Foundation for Alcohol Research and Education, and staff have been highly
      successful in securing additional competitive research funding. In 2016, CAPR
      moved to a new institutional setting at La Trobe University and celebrated 10
      years of operation.

PMID- 29178663
TI  - Ketamine for chronic non-cancer pain: A meta-analysis and trial sequential
      analysis of randomized controlled trials.
AB  - BACKGROUND: Ketamine has been suggested to be efficient in relieving chronic
      pain. However, there is inconsistency across studies investigating the effect of
      ketamine for chronic pain management. We aimed to perform a meta-analysis in
      order to assess the efficacy of this compound during chronic non-cancer pain
      conditions. METHODS: The study consisted in a meta-analysis of clinical trials
      comparing ketamine to a placebo during chronic non-cancer pain. The primary
      endpoint of this study was pain relief 4 weeks after the beginning of treatment.
      Secondary outcomes were: pain relief 1, 2, 8 and 12 weeks after the beginning of
      treatment and incidence of psychedelic manifestations. RESULTS: Six studies were
      included in this meta-analysis. Overall, 99 patients received ketamine and 96
      received placebo. Ketamine did not decrease pain intensity at 4 weeks (MD (on a 0
      to 10 scale) = -1.12 [-2.33, 0.09], GRADE evidence: very low). However, analysing
      studies with no high-risk bias found ketamine to decrease pain intensity at 4
      weeks and increased the level of GRADE evidence to moderate. Trial sequential
      analysis confirmed the overall result and revealed the lack of power of this meta
      analysis. Ketamine also decreased pain intensity at all other evaluated points in
      time. Ketamine increased the incidence of psychedelic manifestations in
      comparison to placebo. CONCLUSION: Results of this meta-analysis found moderate
      evidence suggesting the efficacy of ketamine during chronic pain. Further studies
      are warranted to conclude about the effect of ketamine during chronic pain
      conditions and to determine optimal administration regimes of this agent during
      this condition. SIGNIFICANCE: Ketamine has been found interesting for managing
      chronic pain. We performed a meta-analysis aiming to confirm those results.
      Ketamine was found efficient in alleviating pain up to 12 weeks after the
      beginning of treatment. However, overall evidence favouring the use of this
      compound was very low.

PMID- 29178664
TI  - Environmental enrichment and drug value: a behavioral economic analysis in male
      rats.
AB  - Rats raised in an enriched condition (EC) show decreased stimulant self
      administration relative to rats reared in an isolated condition (IC). However,
      few studies have examined the behavioral mechanisms underlying this environment
      induced difference in self-administration. Because economic demand for drugs of
      abuse predicts addiction-like behavior in both humans and animals, we applied a
      behavioral economic analysis to cocaine self-administration data in EC and IC
      rats. During cocaine self-administration, the dose decreased across blocks of
      trials (0.75-0.003 mg/kg/inf), which allowed for a determination of demand
      intensity and demand elasticity. Demand intensity did not differ between EC and
      IC rats; however, cocaine was more elastic in EC rats relative to IC rats (i.e.
      EC rats were less willing to respond for cocaine as the unit price increased).
      When EC rats were placed in an isolated condition, demand elasticity decreased,
      whereas elasticity increased for IC rats placed in an enriched condition.
      Additionally, we applied behavioral economic analyses to previously published
      self-administration data and found that our results replicate past findings with
      cocaine and methylphenidate. To determine if differences in demand elasticity are
      specific to drug reinforcement, a separate group of rats was tested in sucrose or
      saccharin self-administration. Results showed that sucrose and saccharin were
      more elastic in EC rats relative to IC rats, and demand intensity was lower for
      saccharin in EC rats relative to IC rats. Overall, drug and nondrug reinforcers
      are more elastic in EC rats, which may account for the protective effects of
      environmental enrichment against stimulant self-administration.

PMID- 29178665
TI  - Early impairment of the full-field photopic negative response in patients with
      Stargardt disease and pathogenic variants of the ABCA4 gene.
AB  - BACKGROUND: To study the photopic negative response of the full-field photopic
      electroretinography (ERG) in Stargardt patients with pathogenic variants in the
      ABCA4 gene. METHODS: A retrospective analysis of 35 Stargardt patients with ABCA4
      gene pathogenic variants, compared to normal age-matched controls. Patients were
      clinically followed at the Ophthalmology Department of Fondazione Policlinico
      Universitario A. Gemelli/Universita Cattolica del Sacro Cuore, Rome, Italy.
      RESULTS: The photopic negative response of the full-field photopic ERG was
      compromised in most Stargardt patients. In the presence of a normal B-wave, the
      amplitude ratio between the photopic negative response and the B-wave displayed a
      97% accuracy in detecting diseased eyes (receiver operating characteristic
      curves). CONCLUSIONS: In Stargardt patients with ABCA4 pathogenic mutations, the
      photopic negative response of the full-field photopic ERG is a very sensitive
      disease read-out. Its inclusion in standard ERG analysis would be a no-cost
      addition of practical consequence in the follow-up of Stargardt disease. The
      early impairment of the photopic negative response suggests that inner retinal
      function might be affected in Stargardt disease earlier than previously
      acknowledged.

PMID- 29178666
TI  - Luminescent studies of binuclear ternary europium(III) pyridineoxide tetrazolate
      complexes containing bis-phosphine oxide as auxiliary co-ligands.
AB  - A new class of antenna chromophores so called 'tetrazolates' have not been
      explored much for lanthanide luminescencent complexes. However, we have already
      published several articles considering pyridineoxide tetrazolates as sensitizer
      with lanthanide ions. Although this class of antenna attracted much less
      attention because of its poor photoluminescence quantum yields (tris
      pyridineoxide tetrazolate europium complex = 13% in solution) we tried and
      successfully achieved to improve the photoluminescence quantum yields for this
      particular antenna molecule by replacing coordinated water from the inner
      coordination sphere of europium ion by introducing phosphine oxides as additional
      chromophore. In the present article the two bis-phosphine oxides attach two
      molecules of tris-pyridineoxide tetrazolate europium(III) complex which leads to
      the improvement of the overall molar absorption coefficients as well as photo
      physical properties of the complexes. We found more than two-fold increase (31%
      in solution) in photoluminescence quantum yield with one of the coordinated
      phosphine oxides comparing with that of tris-pyridineoxide tetrazolate
      europium(III) complex.

PMID- 29178667
TI  - Comprehensive review of post-organ transplant hematologic cancers.
AB  - A higher risk for a variety of cancers is among the major complications of
      posttransplantation immunosuppression. In this part of a continuing series on
      cancers posttransplantation, this review focuses on the hematologic cancers after
      solid organ transplantation. Posttransplantation lymphoproliferative disorders
      (PTLDs), which comprise the great majority of hematologic cancers, represent a
      spectrum of conditions that include, but are not limited to, the Hodgkin and non
      Hodgkin lymphomas. The oncogenic Epstein-Barr virus is a key pathogenic driver in
      many PTLD cases, through known and unknown mechanisms. The other hematologic
      cancers include leukemias and plasma cell neoplasms (multiple myeloma and
      plasmacytoma). Clinical features vary across malignancies and location.
      Preventive screening strategies have been attempted mainly for PTLDs. Treatments
      include the chemotherapy regimens for the specific cancers, but also include
      reduction of immunosuppression, rituximab, and other therapies.

PMID- 29178668
TI  - Pseudomonas aeruginosa biofilm hampers murine central wound healing by
      suppression of vascular epithelial growth factor.
AB  - Biofilm-infected wounds are clinically challenging. Vascular endothelial growth
      factor and host defence S100A8/A9 are crucial for wound healing but may be
      suppressed by biofilms. The natural course of Pseudomonas aeruginosa biofilm
      infection was compared in central and peripheral zones of burn-wounded, infection
      susceptible BALB/c mice, which display delayed wound closure compared to C3H/HeN
      mice. Wounds were evaluated histopathologically 4, 7 or 10 days post-infection.
      Photoplanimetry evaluated necrotic areas. P. aeruginosa biofilm suppressed
      vascular endothelial growth factor levels centrally in BALB/c wounds but
      increased peripheral levels 4-7 days post-infection. Central zones of the burn
      wound displayed lower levels of central vascular endothelial growth factor as
      observed 4 and 7 days post-infection in BALB/c mice compared to their C3H/HeN
      counterparts. Biofilm suppressed early, centrally located S100A8/A9 in BALB/c and
      centrally and peripherally later on in C3H/HeN wounds as compared to uninfected
      mice. Peripheral polymorphonuclear-dominated inflammation and larger necrosis
      were observed in BALB/c wounds. In conclusion, P. aeruginosa biofilm modulates
      wounds by suppressing central, but inducing peripheral, vascular endothelial
      growth factor levels and reducing host response in wounds of BALB/c mice. This
      suppression is detrimental to the resolution of biofilm-infected necrosis.

PMID- 29178669
TI  - Identification of polystyrene nanoparticle penetration across intact skin barrier
      as rare event at sites of focal particle aggregations.
AB  - The question whether nanoparticles can cross the skin barrier is highly debated.
      Even in intact skin rare events of deeper penetration have been reported, but
      technical limitations and possible artifacts require careful interpretation. In
      this study, horizontal scanning by 2-photon microscopy (2 PM) of full-thickness
      human skin samples placed in a lateral position yielded highly informative images
      for skin penetration studies of fluorescently tagged nanoparticles. Scanning of
      large fields of view allowed for detailed information on interfollicular and
      follicular penetration in tissue blocks without damaging the sample. Images in
      histomorphological correlation showed that 2P-excited fluorescence signals of
      fluorescently tagged 20 and 200 nm polystyrene nanoparticles preferentially
      accumulated in the stratum corneum (SC) and in the upper part of vellus hair
      follicles (HFs). Rare events of deeper penetration in the SC and in the
      infundibulum of vellus HFs were observed at sites of high focal particle
      aggregations. Wide-field 2 PM allows for imaging of nanoparticle penetration in
      large tissue blocks, whereas total internal reflection microscopy (TIRFM) enables
      selective detection of individual nanoparticles as well as clusters of
      nanoparticles in the SC and within the epidermal layer directly beneath the SC,
      thus confirming barrier crossing with high sensitivity.

PMID- 29178670
TI  - Efficacy and Safety of Subcutaneous Allergen Immunotherapy for Allergic Rhinitis.

PMID- 29178671
TI  - Claudin may be a Potential Biomarker for Epithelial Barrier Dysfunction in
      Asthma.

PMID- 29178672
TI  - Glycolysis and the Hexosamine Biosynthetic Pathway as Novel Targets for Upper and
      Lower Airway Inflammation.
AB  - Glycolysis is a process that rapidly converts glucose to lactate to produce
      adenosine triphosphate (ATP) under anaerobic conditions and occurs in all
      eukaryotic and prokaryotic cells. On the other hand, the hexosamine biosynthetic
      pathway (HBP) converts glucose to intermediate products like UDP-N
      acetylglucosamine, which is critical for post-translational modifications of
      proteins, such as protein glycosylation. These 2 pathways are well known to
      contribute to glucose metabolism, but recent studies indicate modulation of these
      pathways can alter immune system function. In this review article, the authors
      present results suggesting how cellular metabolism, including glycolysis and the
      HBP, occurs in immune cells, and the immunologic significances of such
      activities. In addition, they provide a review of the literature on the effects
      of glycolysis and the HBP on various autoimmune, immunologic, and allergic
      diseases. Finally, the authors briefly introduce the results of their research on
      the immunologic effects of HBP supplementation (glucosamine) in animal models of
      allergic disease.

PMID- 29178673
TI  - Viral Infections and Associated Factors That Promote Acute Exacerbations of
      Asthma.
AB  - Despite asthma being the most common chronic childhood ailment, there is still
      much to learn about the disease. Early childhood infections with well-known or
      emerging viruses can lay the pathophysiologic framework for asthma development
      and exacerbation later in life, which may be due partly to alteration of the
      airway microbiome. Once asthma is established, acute exacerbations are usually
      associated with infections with respiratory viruses, such as rhinoviruses (RVs).
      Once again, there are bidirectional interactions between viruses and airway
      bacteria that appear to influence the severity of illness and the likelihood of
      exacerbation. Studies employing recent advances in viral and bacterial
      identification analytic techniques will clarify these new concepts and may
      provide the basis for new treatments or prevention or respiratory infection
      associated exacerbation. This paper is a review of the associations among
      respiratory viruses, bacteria, inflammatory mechanisms, and asthma exacerbation.

PMID- 29178674
TI  - A Retrospective Study of Clinical Response Predictors in Subcutaneous Allergen
      Immunotherapy With House Dust Mites for Allergic Rhinitis.
AB  - PURPOSE: House dust mites (HDM) are major allergens that cause allergic rhinitis
      (AR). Allergen-specific subcutaneous immunotherapy (SCIT) has been shown to be
      clinically beneficial in many clinical trials. Such trials, however, are not
      reflective of all patient populations. The aim of this study was to describe the
      efficacy and safety of SCIT in routine clinical practice in Korean adults with AR
      sensitized to HDM. METHODS: We reviewed medical records of 304 patients with AR
      treated at an allergy clinic of a tertiary hospital using SCIT with aluminum
      hydroxide-adsorbed allergen extract targeting HDM alone or with pollens for at
      least 1 year from 2000 to 2012. Patients with asthma were excluded. Rates of
      remission, defined as no further requirement of maintenance medication, over time
      were determined by means of life tables and extension of survival analysis.
      Specific immunoglobulin E (IgE) levels to HDM were categorized into 6 classes.
      RESULTS: The mean time until achieving remission was 4.9+/-0.1 years, and the
      cumulative incidence of remission from AR was 76.6%. Severe AR (odds ratio [OR],
      0.40; 95% confidence interval [CI], 0.23-0.69; P=0.001), specific IgE levels to
      HDM >=17.5 kU/L (OR, 1.85; 95% CI, 1.01-3.37; P=0.045), and duration of
      immunotherapy >=3 years (OR, 7.37; 95% CI, 3.50-15.51; P<0.001) were identified
      as significant predictors of clinical remission during SCIT for patients with AR
      sensitized to HDM. Overall, 73 patients (24.0%) experienced adverse reactions to
      SCIT, and only 1 case of anaphylaxis (0.3%) developed. CONCLUSIONS: SCIT with HDM
      was found to be effective and safe for patients with AR. Specific IgE levels to
      HDM and a duration of SCIT >=3 years may be predictors of clinical responses to
      SCIT in AR patients.

PMID- 29178675
TI  - Alteration in Claudin-4 Contributes to Airway Inflammation and Responsiveness in
      Asthma.
AB  - PURPOSE: Claudin-4 has been reported to function as a paracellular sodium barrier
      and is one of the 3 major claudins expressed in lung alveolar epithelial cells.
      However, the possible role of claudin-4 in bronchial asthma has not yet been
      fully studied. In this study, we aimed to elucidate the role of claudin-4 in the
      pathogenesis of bronchial asthma. METHODS: We determined claudin-4 levels in
      blood from asthmatic patients. Moreover, using mice sensitized and challenged
      with OVA, as well as sensitized and challenged with saline, we investigated
      whether claudin-4 is involved in the pathogenesis of bronchial asthma. Der p1
      induced the inflammatory cytokines in NHBE cells. RESULTS: We found that claudin
      4 in blood from asthmatic patients was increased compared with that from healthy
      control subjects. Plasma claudin-4 levels were significantly higher in
      exacerbated patients than in control patients with bronchial asthma. The plasma
      claudin-4 level was correlated with eosinophils, total IgE, FEV1% pred, and
      FEV1/FVC. Moreover, lung tissues from the OVA-OVA mice showed significant
      increases in transcripts and proteins of claudin-4 as well as in TJ breaks and
      the densities of claudin-4 staining. When claudin-4 was knocked down by
      transfecting its siRNA, inflammatory cytokine expressions, which were induced by
      Der p1 treatment, were significantly increased. CONCLUSIONS: These findings thus
      raise the possibility that regulation of lung epithelial barrier proteins may
      constitute a therapeutic approach for asthma.

PMID- 29178676
TI  - Chinese Herbal Medicine to Treat Allergic Rhinitis: Evidence From a Meta
      Analysis.
AB  - PURPOSE: Chinese herbal medicine (CHM) has been widely used in China to treat
      allergic rhinitis (AR). However, several studies have produced conflicting data
      with regard to the efficacy of the medicine. Our aim was to perform a meta
      analysis of randomized clinical trials (RCTs) to evaluate the relative efficacy
      of CHM. METHODS: We systematically searched the PubMed, Medline, and Springer
      electronic databases up to March 2017 for RCTs comparing the efficacy of CHM
      versus placebo for the treatment of patients with AR. Total nasal symptoms and
      quality of life were assessed through pooling mean difference (MD) with its 95%
      confidence interval (CI). Moreover, sensitivity and subgroup analyses according
      to control design and quality of life assessment were performed to evaluate the
      source of heterogeneity. RESULTS: Eleven RCTs were enrolled in the meta-analysis.
      Assessment of overall heterogeneity indicated significant heterogeneity among the
      individual studies (I2=100%, P<0.00001), and thus ransomed effects model was used
      to pool data. CHM was found to significantly enhance quality of life compared
      with placebo (MD=-0.88, (95% CI: -1.55, -0.21); P=0.01). The symptom of itchy
      nose, sneezing or total nasal symptoms scores were not significantly improved
      after CHM treatment, although the improvement in itchy nose just failed to reach
      significance (MD=0.09, (95% CI: 0.00, 0.18); P=0.06). CONCLUSIONS: This study
      suggests that CHM appears to improve the quality of life of AR patients. However,
      these findings, as well as the findings for the effect of CHM on sneezing, total
      nasal symptoms, and the symptom of itchy nose, need to be substantiated in larger
      cohorts of AR patients by further well-designed studies.

PMID- 29178677
TI  - Respiratory Function and Symptoms Post Cold Air Exercise in Female High and Low
      Ventilation Sport Athletes.
AB  - PURPOSE: Cold weather exercise is common in many regions of the world; however,
      it is unclear whether respiratory function and symptom worsen progressively with
      colder air temperatures. Furthermore, it is unclear whether high-ventilation
      sport background exacerbates dysfunction and symptoms. METHODS: Seventeen active
      females (measure of the maximum volume of oxygen [VO(2max)]: 49.6+/-6.6 mL.kg
      1.min-1) completed on different days in random order 5 blinded running trials at
      0 degrees C, -5 degrees C, -10 degrees C, -15 degrees C, and -20 degrees C
      (humidity 40%) in an environmental chamber. Distance, heart rate, and rating of
      perceived exertion (RPE) were measured within each trial; forced expiratory
      volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at
      25%-75% (FEF25-75), and forced expiratory flow at 50% (FEF50) were measured pre-
      and post-test (3, 6, 10, 15, and 20 minutes). Respiratory symptoms and global
      effort were measured post-test spirometry. RESULTS: Mean decreases were found in
      FEV1 (4%-5% at 0 degrees C, -5 degrees C, -10 degrees C, and -15 degrees C; 7% at
      -20 degrees C). FEF25-75 and FEF50 decreased 7% and 11% at -15 degrees C and -20
      degrees C, respectively. Post-exertion spirometry results were decreased most at
      3 to 6 minutes, recovering back to baseline at 20 minutes. Respiratory symptoms
      and global effort significantly increased at -15 degrees C and -20 degrees C with
      decreased heart rate. High-ventilation sports decreased function more than low
      ventilation participants but had fewer symptoms. CONCLUSIONS: These results
      indicate that intense exercise at cold air temperatures up to -20 degrees C is
      achievable; however, greater effort along with transient acute
      bronchoconstriction and symptoms of cough after exercising in temperatures colder
      than -15 degrees C are likely. It is recommended that individuals cover their
      mouth and reduce exercise intensity to ameliorate the effects of cold weather
      exercise.

PMID- 29178678
TI  - beta2-Adrenoceptor Blockade Deteriorates Systemic Anaphylaxis by Enhancing
      Hyperpermeability in Anesthetized Mice.
AB  - PURPOSE: Patients treated with propranolol, a nonselective beta-adrenoceptor
      antagonist, develop severe anaphylaxis, but the mechanism remains unknown. We
      determined effects of beta1- and beta2-adrenoceptor antagonists on the
      anaphylaxis-induced increase in vascular permeability in mice. METHODS: In
      anesthetized ovalbumin-sensitized C57BL mice, mean arterial blood pressure (MBP)
      was measured, and Evans blue dye extravasation and hematocrit (Hct) were assessed
      at 20 minutes after antigen injection. The following pretreatment groups
      (n=7/group) were studied: (1) sensitized control (non-pretreatment), (2)
      propranolol, (3) the selective beta2-adrenoceptor antagonist ICI 118,551, (4) the
      selective beta1-adrenoceptor antagonist atenolol, (5) adrenalectomy, (6) the
      selective beta2-adrenoceptor agonist terbutaline, and (7) non-sensitized groups.
      RESULTS: The antigen injection decreased MBP, and increased Hct and vascular
      permeability in the kidney, lung, mesentery, and intestine, but not in the liver
      or spleen. Pretreatment with ICI 118,551, propranolol and adrenalectomy, but not
      atenolol, reduced the survival rate and augmented the increases in Hct and
      vascular permeability in the kidney, intestine, and lung as compared with the
      sensitized control group. Pretreatment with terbutaline abolished the antigen
      induced alterations. Plasma epinephrine levels were increased significantly in
      the sensitize control mice. CONCLUSIONS: Blockade of beta2-adrenoceptor can
      deteriorate systemic anaphylaxis by augmenting hyperpermeability-induced increase
      in plasma extravasation by inhibiting beneficial effects of epinephrine released
      from the adrenal glands in anesthetized mice.

PMID- 29178679
TI  - Detecting Allergens From Black Tiger Shrimp Penaeus monodon That Can Bind and
      Cross-link IgE by ELISA, Western Blot, and a Humanized Rat Basophilic Leukemia
      Reporter Cell Line RS-ATL8.
AB  - BACKGROUND: Black tiger shrimp Penaeus monodon is one of the common causes of
      shellfish allergy that is increasing worldwide. One of the important problems in
      the management of shellfish allergy is the lack of accurate diagnostic assay
      because the biological and immunological properties of allergens in black tiger
      shrimp have not been well characterized. This study aims to detect proteins with
      the ability to bind and cross-link immunoglobulin E (IgE) from black tiger shrimp
      by enzyme-linked immunosorbent assay (ELISA), Western blot, and a humanized rat
      basophilic leukemia reporter cell line RS-ATL8. METHODS: Sera from shrimp
      allergic subjects were subjected to ELISA and Western blots using raw or cooked
      shrimp extract as antigens. Pooled sera were used to sensitize the RS-ATL8
      reporter cell line and cells were activated by shrimp extract. Eluted protein
      extracts separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE) were tested on the RS-ATL8 cell line and subjected to mass
      spectrometry to identify potential candidate allergens. RESULTS: Allergic sera
      reacted stronger to raw shrimp extract than cooked shrimp extract (P=0.009).
      Western blot demonstrated that major IgE reactivity protein bands were at 32-39
      kDa and 91-230 kDa in both raw and cooked shrimp extracts. The eluted protein
      bands at the molecular weight of 38 and 115 kDa from raw shrimp extract induced
      IgE cross-linking as assayed by the RS-ATL8 cell line. These protein bands were
      subjected to mass spectrometry for analysis. Ubiquitin-activating enzyme and
      crustacyanin were identified as potential candidate novel shrimp allergens.
      CONCLUSIONS: The RS-ATL8 reporter cell line can be used to identify potential new
      shrimp allergens that can functionally cross-link IgE and induce mast cell
      degranulation.

PMID- 29178680
TI  - T-Helper Type 2 Cells Direct Antigen-Induced Eosinophilic Skin Inflammation in
      Mice.
AB  - Eosinophilic inflammation in combination with immunoglobulin E (IgE) production
      is a characteristic feature of atopic dermatitis. Although activated T-helper
      type (Th) 2 cells play critical roles in the local accumulation and activation of
      eosinophils, whether they induce eosinophilic skin inflammation, independent of
      the IgE-mediated pathway has been unclear. To address the functional role of T
      cells in allergic skin diseases, we herein transferred Th1/Th2-differentiated or
      naive DO11.10 T cells into unprimed BALB/c mice. Ovalbumin-specific Th2 cells, as
      well as eosinophils, accumulated in the skin upon antigen challenge, despite the
      absence of antigen-specific IgE. Neither antigen-specific Th1 nor naive T cells
      induced eosinophil accumulation, although Th1 cells by themselves migrated into
      the skin. Interleukin (IL)-4, IL-5, and eotaxin were specifically produced in the
      skin of antigen-challenged, Th2 cell-transferred mice, whereas interferon (IFN)
      gamma and regulated on activation, normal T cell expressed and secreted (RANTES)
      were preferentially produced in Th1 cells-transferred mice. Production of
      monocyte chemoattractant protein (MCP)-1 and MCP-3 was enhanced by both Th1 and
      Th2 cells. The accumulation of eosinophils and Th2 cells in the skin was
      suppressed by both dexamethasone and FK506, indicating an essential role of Th2
      cells in eosinophil recruitment. We conclude that Th2 cells can induce
      eosinophilic infiltration into the skin in the absence of antigen-specific IgE.

PMID- 29178681
TI  - Clinical Course of Chronic Spontaneous Urticaria in the Korean Adult Population.
AB  - Knowledge of the clinical course of chronic spontaneous urticaria (CSU) remains
      unclear. The purpose of our study was to investigate the clinical course of CSU
      in the Korean adult population. Each patient in the CSU group who was defined by
      disease codes between 2003 and 2007 was tracked whether he or she went into
      remission or not until 2013. Kaplan-Meier survival analysis was carried out to
      analyze remission, and log-rank tests were performed for between-group
      comparisons. Demographic differences between subjects who went into remission 1
      year after the initial diagnosis and those who did not were analyzed using chi2
      tests. A total of 13,969 subjects were included in the CSU group. The 1-, 2-, 3-,
      4-, and 5-year remission rates of CSU were 21.5%, 33.0%, 38.9%, 42.6%, and 44.6%,
      respectively. The proportion of subjects in the 65+ age group (P=0.050) and with
      male gender (P=0.002) was significantly higher among subjects who did not go into
      remission 1 year after the initial diagnosis. Our study indicates that CSU could
      have a more persistent course than previously reported.

PMID- 29178683
TI  - Reducing Anticholinergic Medication Burden in Patients With Psychotic or Bipolar
      Disorders.
AB  - OBJECTIVE: Anticholinergic medications are prescribed to treat extrapyramidal
      side effects (EPS) associated with antipsychotics. Anticholinergic medications
      cause several side effects and can often be withdrawn during the maintenance
      phase of antipsychotic treatment without EPS reemergence. The purpose of this
      quality improvement (QI) project was to reduce anticholinergic medication burden
      and improve quality of life in patients with severe mental illness. METHODS:
      Patients with DSM-IV-TR-diagnosed schizophrenia, schizoaffective disorder, and
      bipolar disorders in an outpatient psychiatric clinic who were prescribed
      benztropine were identified, screened for anticholinergic side effects by the
      treating psychiatrist, and referred to an on-site clinical pharmacist for a
      comprehensive medication review. Anticholinergic side effects, cognitive
      impairment, and impact on quality of life were assessed using a Likert scale.
      Recommendations for potential medication changes were discussed with the
      prescriber. Initial and follow-up assessments were conducted over 1-8 months to
      identify improvements in side effects and quality of life. RESULTS: Twenty-nine
      patients were assessed from November 2014 to December 2015. Patients were
      receiving from 1 to 6 medications with anticholinergic properties (median = 3
      medications). Of the 29 patients, 19 were recommended for a medication change,
      with 13 having 1 or more anticholinergic medications discontinued and 6 having
      the dose decreased. A significant reduction in anticholinergic side effects and
      improvements in memory and quality of life were observed for these patients (P <=
      .05). CONCLUSIONS: In this interdisciplinary, collaborative QI project, patients
      whose anticholinergic burden was reduced experienced a significant improvement in
      side effects, memory, and quality of life.

PMID- 29178682
TI  - Real-Life Clinical Use of Symbicort(r) Maintenance and Reliever Therapy for
      Asthmatic Patients in Korea.
AB  - The aim of this study was to examine the daily practice patterns of Symbicort(r)
      Maintenance and Reliever Therapy (SMART) in Korean asthmatic patients and to
      analyze clinical signs related to overuse. This study used an observational,
      multicenter, noninterventional, prospective, uncontrolled design for examining
      asthmatic patients prescribed SMART to assess the frequency and pattern of
      Symbicort(r) usage as a maintenance and reliever medication. The characteristics
      of patients showing signs of overuse (frequency of inhalation: 8 or more times
      per day) were also analyzed. Among the 1,518 patients analyzed, 1,292 (85.1%)
      completed the trial. The number of mean inhalations per day was 2.14+/-1.15; the
      number of patients who had at least 1 as needed usage (PRN) inhalation per day
      was 843 (55.5%); the mean frequency of PRN use was 0.25+/-0.67 inhalations per
      day. The number of patients who overused for at least 1 day was 260 (17.1%). In
      particular, young patients, patients with limited physical activity, and patients
      with nocturnal symptoms demonstrated high frequency of overuse. The frequency of
      overuse during SMART was not high in Korean asthmatic patients and the asthma
      status of follow-up outpatients improved overall. However, there is a need for
      careful education targeted toward younger patients, patients with limited
      physical activity, and patients with nocturnal symptoms owing to their tendency
      to frequently overuse.

PMID- 29178685
TI  - Clinical and Genetic Predictors of Delayed Remission After Multiple Levels of
      Antidepressant Treatment: Toward Early Identification of Depressed Individuals
      for Advanced Care Options.
AB  - OBJECTIVE: To identify clinical and genetic characteristics that can be used to
      recognize depressed patients who are likely to respond quickly versus those who
      will have a more delayed response following multiple treatment trials. METHODS:
      The data used were obtained from the National Institute of Mental Health
      sponsored Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study,
      which was conducted between July 2001 and September 2006. Of the 4,041 treatment
      naive participants in the original study, 1,953 with DNA samples were included.
      Major depressive disorder (DSM-IV criteria) was defined as baseline score > 14 on
      the 17-item Hamilton Depression Rating Scale. Time to remission was defined from
      the entry point to when a score <= 5 on the Quick Inventory of Depressive
      Symptomatology, Clinician Rating was achieved, irrespective of the type or number
      of treatments received. A Kaplan-Meier estimator was used for data description,
      proportional hazard regression for model building, and logistic regression for
      measures of predictive accuracy. RESULTS: The overall rate of remission across
      all levels of treatment was 65.6%, and the overall median (interquartile range)
      of time to remission was 11.4 (6.0-17.9) weeks. The predictors of delayed
      remission included unemployment (P = .004), severe medical comorbidity (P <
      .0001), severe baseline depression (P < .0001), more than 4 dysthymic symptoms (P
      = .005), more than 9 posttraumatic stress symptoms (P = .005), and serotonin
      receptor 1A (P = .006) and cytochrome P450 2D6 (P = .002 for C/T and P = .0004
      for T/T) genetic variants. The final model had good predictive measures of
      accuracy of area under the curve (70%) and sensitivity (88%). CONCLUSIONS: The
      results offer clinical tools for clinicians to identify depressed individuals who
      are likely to have delayed remission with multiple antidepressant treatments and
      therefore might be candidates for advanced care options.

PMID- 29178686
TI  - Memantine as an Augmentation Treatment for Schizophrenia: Limitations of Meta
      Analysis for Evidence-Based Evaluation of Research.
AB  - The action of memantine on N-methyl-D-aspartate (NMDA) glutamatergic receptors
      and the other pharmacodynamic actions of this drug suggest that it may benefit
      patients with schizophrenia. Many randomized controlled trials (RCTs) have
      examined this possibility. These RCTs have been meta-analyzed by at least 2
      groups of authors. In one meta-analysis (8 RCTs, pooled N = 448), memantine (20
      mg/d for 6-12 weeks) augmentation of antipsychotic drug therapy was found to
      attenuate the severity of negative symptoms and improve cognitive functioning; in
      both regards, the effect was large. Memantine was also associated with a small
      but statistically significant reduction in general psychopathology. Whereas
      memantine did not significantly attenuate positive symptom, depression, total
      psychopathology, and global illness ratings, it was also not associated with an
      increased risk of individual adverse events, discontinuation due to adverse
      events, or all-cause discontinuation. The findings of the other meta-analysis,
      which examined much the same body of literature, were largely similar. On the
      surface, these results suggest that memantine may be considered for the reduction
      of negative symptoms and cognitive impairment in schizophrenia. However, an
      examination of the individual RCTs and a careful look at the findings of the meta
      analyses identify so many important concerns that it is probably premature to
      draw conclusions about the usefulness of memantine as an augmentation strategy in
      schizophrenia. At best, it may be stated that there is a signal that supports the
      study of memantine in schizophrenia patients who are specifically impaired by
      negative symptoms and cognitive complaints. This is a good example of a situation
      in which meta-analysis did not provide a trustable evidence-based interpretation
      of literature.

PMID- 29178684
TI  - A Supervised Exercise Intervention for Youth at Risk for Psychosis: An Open-Label
      Pilot Study.
AB  - OBJECTIVE: A rapidly accumulating body of research suggests that exercise can
      improve symptoms and well-being in patients suffering from psychosis. Exercise
      may also promote neurogenesis in the hippocampus, a structure that plays an
      important role in the pathophysiology of psychosis. To date, there has not been
      an intervention focused on exercise prior to the onset of psychosis, a critical
      time for prevention of more serious illness. METHODS: In this pilot study, 12
      young adults at ultrahigh risk (UHR) for psychosis were enrolled in a 12-week
      open-label exercise intervention. Participants were randomly assigned to exercise
      2 or 3 times each week and exercised between 65% and 85% of maximum oxygen
      capacity (Vo2max) for 30 minutes each session under the supervision of an
      exercise physiologist. Positive and negative symptoms, social and role
      functioning, performance on neurocognitive tests, cardiovascular fitness, and
      hippocampal structure and functional connectivity were evaluated before and after
      the trial. RESULTS: A total of 9 participants completed the exercise
      intervention. Participants showed improved positive and negative symptoms and
      social and role functioning; improvement in multiple areas of cognition; and
      increased functional connectivity between the left hippocampus and occipital
      cortex after 12 weeks of exercise. CONCLUSIONS: The results of this study suggest
      that exercise interventions are feasible in a UHR sample and may promote
      improvement in clinical, social, and cognitive domains as well as changes to
      brain function in regions impacted by the development of psychosis. These
      findings set the stage for an ongoing phase 2 randomized controlled trial. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT02155699.

PMID- 29178687
TI  - ?

PMID- 29178688
TI  - ?

PMID- 29178689
TI  - ?

PMID- 29178690
TI  - [Cost evaluation of organ harvesting in a Belgian academic hospital].
AB  - INTRODUCTION: The aim of this study is (1) to describe the characteristics of the
      organ harvesting activity conducted in 2012 at the Erasme's Hospital, Brussels
      University Hospital, (2) to highlight the different combinations " type of
      donor/types of organ's retrieved " in relation to organ harvestings carried out
      within the hospital, and (3) to calculate the organ harvesting's cost of acts.
      METHODS: The study is conducted according to the hospital perspective. It
      assesses the consumption of medical and nursing staff resources, disposable
      material costs, medical device costs, drugs costs, sterile instruments and
      biomedical equipment costs, of the 34 organ harvesting procedures that has been
      conducted this year. Costs are calculated by procedure, by donor's type, by organ
      and by combinations. RESULTS: Total cost is 99.442 ?, with an average cost per
      donor of 3.016 ?, 3.292 ? for DBD postmortem donor (Donor Brain Death) and 2.456
      ? for DCD type (Donor Cardio-Circulatory Death). The average cost per organ
      leading to a transplantation is 1.842 ? for DCD type and 1.297 ? for DBD.
      CONCLUSION: The results show that there is as many costs as the number of organ
      harvesting's combinations. Integrate the revenue generated by organ harvestings
      could establish whether funding sources cover the costs generated by this
      activity or if a reform of the nomenclature should be considered.

PMID- 29178691
TI  - [Analysis of positive margins risk factors and long term recurrence in the
      conservative treatment of breast cancer].
AB  - INTRODUCTION: breast conserving therapy remains the first choice in breast cancer
      care for the early stages. Adequate surgical margins are essential to reduce the
      risk of locoregional recurrence. This study aims to identify risk factors of
      positive margins and locoregional recurrence. MATERIALS AND METHODS: 437 patients
      who underwent a lumpectomy for invasive breast carcinoma or ductal carcinoma in
      situ have been included. Age, surgical margins, size, type, grade and number of
      tumor foci, the presence of ductal carcinoma in situ, lymph node status,
      expression of hormone receptors and HER-2 gene were assessed as risk factors for
      positive margins and locoregional recurrence. RESULTS: The disease-free survival
      is 94 % at 10 years. Patients with positive margins have lower survival (92 %)
      than those with negative margins (96 %) (p L 0.05). Lobular and multifocal tumors
      are at risk of positive margins. Tumors with positive margins, T2, grade III,
      triple negative and HER-2 positive neoplasms are at risk of locoregional
      recurrence while the expression of hormone receptors is a protective factor for
      local recurrence. CONCLUSION: It appears in our study that invasive lobular and
      multifocal tumors may present positive surgical margins. Studies on pre-
      operative work-up are needed. Biological factors of the tumor seem to play a
      fundamental role in the locoregional recurrence or persistence of the tumor.

PMID- 29178692
TI  - [Management of vaccination in children receiving an allogeneic marrow
      transplant].
AB  - Over the last decades, significant advances in the diagnosis and therapeutics
      have considerably improved success rate from bone marrow transplant in patients
      suffering from otherwise life-threatening diseases, allowing now for prolonged
      survival and better quality of life after an allograft. However, infectious
      diseases remain one of the most serious complication in this population, hence
      associated with a high morbidity and mortality. Prevention, in particular through
      vaccination, constitutes a cornerstone of the management of immunocompromised
      hosts, since this procedure aims to protect them once back to life in community
      after long periods of hospitalization. If the necessity of vaccinating
      immunocompromised patients as well as their family is unequivocally recognized
      among health care workers, some questions remain source of debate. Several famous
      societies edited guidelines, but those differ from each other and cannot be
      transposed from a country to another without considering their local epidemiology
      and implemented vaccination schedule. Moreover, development and availability of
      new vaccines render recommendations constantly susceptible to adaptations. After
      exhaustive literature review, this article aims to offer pragmatic answers to the
      main questions raised by healthcare workers when vaccinating children after a
      bone marrow transplant. We here review all vaccines available and discuss their
      modalities of administration considering the timing after transplant, the
      immunological residual status and the medical history of the child. We also offer
      clues to optimize vaccination of patients' siblings. In addition to highlight
      some interrogations about future vaccines formulations, we propose here a
      vaccination schedule tailored for pediatric bone marrow transplant recipients in
      Belgium in 2017.

PMID- 29178693
TI  - [News Skin lesions : a case report of fixed drug eruption].
AB  - Fixed drug eruption is an erythematous eruption of one or more centimetric
      rounded or oval lesions well demarcated, recurrent at the same place and leaving
      a residual purple pigmentation. Diagnosis is clinical. Skin biopsy is not
      essential except in doubtful cases (eg bullous drug eruption can simulate Lyell
      Syndrome or mucosal reminiscent of erythema multiforme). The etiology is almost
      always drug-induced; rare cases of toxic or food issue were reported.
      Histopathology is immuno-allergic; recurrences correspond to re-exposure to
      allergen. There is no specific treatment except stopping the causing drug.

PMID- 29178694
TI  - ?

PMID- 29178695
TI  - ?

PMID- 29178696
TI  - [Why the name "Erasmus" for an hospital ?]
AB  - Why the name "Erasmus" for an hospital ? Apart for local circumstances, there are
      far more obvious reasons for this choice. Erasmus was in close contact with the
      medical world. Indeed, he suffered all his life from more or less severe diseases
      and had therefore frequent contacts with doctors. Also, the ideas he was
      defending stood for the principle of free inquiry before its time. For these
      various reasons giving the name " Erasmus " to the university clinics of the Free
      University of Brussels (ULB) was a judicious choise.

PMID- 29178697
TI  - Complex signal-based optical coherence tomography angiography enables in vivo
      visualization of choriocapillaris in human choroid.
AB  - The choriocapillaris (CC) plays an essential role in maintaining the normal
      functions of the human eye. There is increasing interest in the community to
      develop an imaging technique for visualizing the CC, yet this remains
      underexplored due to technical limitations. We propose an approach for the
      visualization of the CC in humans via a complex signal-based optical
      microangiography (OMAG) algorithm, based on commercially available spectral
      domain optical coherence tomography (SD-OCT). We show that the complex signal
      based OMAG was superior to both the phase and amplitude signal-based approaches
      in detailing the vascular lobules previously seen with histological analysis.
      With this improved ability to visualize the lobular vascular networks, it is
      possible to identify the feeding arterioles and draining venules around the
      lobules, which is important in understanding the role of the CC in the
      pathogenesis of ocular diseases. With built-in FastTracTM and montage scanning
      capabilities, we also demonstrate wide-field SD-OCT angiograms of the CC with a
      field of view at 9*11  mm2.

PMID- 29178698
TI  - Effects of riboflavin, calcium-phosphate layer and adhesive system on stress
      strain behavior of demineralized dentin.
AB  - PURPOSE: To evaluate if three dentin treatments improved mechanical properties of
      demineralized dentin. METHODS: Dentin slices were demineralized and treated with
      a universal adhesive, Scotchbond Universal (SBU), a cross-linker, Riboflavin
      (RF), and a calcium phosphate-based product, Teethmate (TM). The groups (n= 8 per
      group) were: Group 1: SBU, Group 2: RF + SBU, Group 3: RF + TM + SBU. Tensile
      tests were performed; stress/strain curves and E modulus were calculated.
      Differences between groups were assessed by one-way ANOVA and Duncan post hoc
      test. RESULTS: At high strains, no significant differences in E moduli were
      observed between dentin specimens treated only with SBU and those treated with RF
      + SBU. A significantly higher E modulus was observed in dentin specimens treated
      with RF + TM + SBU. In the presence of an adhesive system, crosslinking collagen
      with RF and TM addition significantly improved mechanical properties of dentin.
      CLINICAL SIGNIFICANCE: Restitution of mineral content into dentin, in addition to
      collagen strengthening, may significantly improve mechanical properties of
      previously demineralized dentin, when covered by an adhesive system in a
      reasonable clinical timeframe.

PMID- 29178699
TI  - Differences in physical characteristics and sealing ability of three tricalcium
      silicate-based cements used as root-end-filling materials.
AB  - PURPOSE: To evaluate differences in physical characteristics and sealing ability
      of root-end-fillings made with these materials compared to the gold standard
      (ProRoot MTA). METHODS: The physical characteristics of ProRoot MTA, Medcem MTA
      and Biodentine were evaluated regarding setting time, flow, film thickness,
      solubility and radiopacity according to the German Institute for Standardization
      (EN-ISO 6878). To investigate their sealing ability as root-end-fillings, a
      glucose penetration model was used. 60 human extracted single-rooted teeth were
      endodontically treated, root-end resections performed and divided in three groups
      of 20 teeth, using either ProRoot MTA, Medcem MTA or Biodentine as root-end
      filling material. After 30 days, glucose concentrations were determined
      photometrically, followed by statistical analysis (Kruskal-Wallis test, Mann
      Whitney U-test). RESULTS: Biodentine showed the fastest setting time (< 12
      minutes) and lowest film thickness (0.11+/- 0.01 mm), whereas Medcem MTA showed
      the best values regarding solubility (< 0.1%) and flow (9.5+/- 0.02 mm). ProRoot
      MTA revealed the highest radiopacity (7.58+/- 0.1 mm aluminum equivalent). The
      glucose leakage in the Medcem MTA group was significantly lower than in the
      ProRoot MTA group (P= 0.011). Biodentine showed lower leakage than ProRoot MTA
      (P= 0.031). CLINICAL SIGNIFICANCE: As Medcem MTA showed significantly lower
      leakage than the other materials tested, it may be an alternative for root-end
      fillings with comparable physical characteristics to the current gold standard.
      With the exception of the high solubility, Biodentine performed well regarding
      leakage and setting time.

PMID- 29178700
TI  - Comparison of different maintenance strategies within supportive implant therapy
      for prevention of peri-implant inflammation during the first year after implant
      restoration. A randomized, dental hygiene practice-based multicenter study.
AB  - PURPOSE: This randomized clinical multicenter study compared different
      professional preventive approaches on peri-implant inflammation under supportive
      implant therapy (SIT). METHODS: 105 participants (167 implants) were randomly
      allocated to four groups. All participants were under SIT with a 3-month recall
      interval. Plaque removal was performed by using manual curettes, a sonic-driven
      scaler, and a prophylaxis brush (Group A), supplemented by chlorhexidine (CHX)
      varnish on the implant surfaces (Group C) or by using manual curettes, air
      polishing with glycine powder, and a prophylaxis brush (Group B), supplemented by
      treatment with CHX varnish on the implant surfaces (Group D). The peri-implant
      probing depths (PPD), mucosal recession (MR), and bleeding on probing (BOP) on
      implants were determined at baseline. After 12 months, the final PPD, MR, and BOP
      on implants were assessed. The statistical evaluation consisted of Kruskal-Wallis
      test, Wilcoxon-test and Chi-squared test modified according to McNemar (P< 0.05).
      RESULTS: 62 subjects (n= 101 implants) were available for assessment. In Groups
      A, C, and D, no significant implant-related differences between baseline and
      follow-up were found in PPD, MR, and BOP. Group B showed a significant difference
      (P= 0.022) between baseline (1.77 +/- 1.58 mm) and follow-up (2.31 +/- 1.54 mm)
      in PPD. The location of implant (P= 0.02), the type of implant (P= 0.01), and the
      age of subject (P= 0.04) had significant influences on BOP. CLINICAL
      SIGNIFICANCE: All strategies were effective in preventing peri-implant
      inflammation. The supplemental application of chlorhexidine varnish had no
      significant additional benefit.

PMID- 29178701
TI  - Fracture resistance of endodontically-treated mandibular molars restored with
      different intra-radicular techniques.
AB  - PURPOSE: To evaluate fracture resistance and failure mode of endodontically
      treated mandibular molars restored with different intra-radicular techniques.
      METHODS: 75 human mandibular molars were randomly divided into five equal groups.
      Teeth were standardized, endodontically-treated and restored according the
      assigned group as follows: amalgam core only, prefabricated titanium post in the
      distal canal and amalgam core, composite core only; fiber post in the distal
      canal and composite core. One group of untreated sound teeth was used as a
      control. Non-precious metal crowns were fabricated and cemented on the prepared
      specimens with Rely X U200 resin cement. All specimens were subjected to a
      compressive load at crosshead speed 0.5 mm/minute, 25 degrees  to the long axis
      of the tooth. Failure loads and modes were recorded. RESULTS: Mean failure loads
      among the groups were significantly different (P= 0.035). Post-hoc multiple pair
      wise comparisons revealed the amalgam core and composite core groups produced
      significantly lower fracture resistance than the control group (P= 0.041 and P=
      0.025, respectively) and no significant differences among the different intra
      radicular techniques (P> 0.05). The composite core with fiber post and amalgam
      core with titanium posts showed the highest percentage of favorable failures
      (67%) and non-favorable failures (87%) respectively. CLINICAL SIGNIFICANCE: The
      composite core with fiber post is the most appropriate intraradicular restoration
      in cases of severely compromised molars.

PMID- 29178702
TI  - Clinical efficacy of resin-based materials for dentin hypersensitivity treatment.
AB  - PURPOSE: To evaluate the effect of three resin-based materials in the treatment
      of dentin hypersensitivity (DH) up to a 6-month follow-up. METHODS: 30
      participants (179 teeth) with DH were enrolled in this randomized, double-blind,
      controlled clinical study. The teeth were randomly allocated into one of three
      groups: CV (resin-modified glass ionomer varnish - Clinpro XT Varnish), CP
      (fluoride-containing self-etch adhesive - Clearfil SE Protect) and GB
      (glutaraldehyde-containing etch-and-rinse adhesive - Gluma 2 Bond). The materials
      were applied according to the manufacturer's instructions. DH was evaluated by
      subjects' perception measured on a 0-10 visual analog scale (VAS) after
      evaporative (air blast) stimuli. The scores were recorded at baseline,
      immediately and at 1, 3 and 6 months after treatment. The data were analyzed by a
      two-way ANOVA with repeated measures for "time" and Games-Howell test (alpha =
      0.05). RESULTS: ANOVA detected statistically significant differences among the
      time intervals, but not among the materials or interactions. There was a
      significant decrease in sensitivity scores from baseline to all the time points
      (P< 0.05). However, the differences were not statistically significant among the
      follow-ups, from immediately until 6 months after treatment (P> 0.05). All the
      resin-based materials were able to reduce DH up to 6 months after treatment.
      CLINICAL SIGNIFICANCE: Resin-based materials used as desensitizing agents were
      effective in reducing DH after a 6-month period and so could be recommended as a
      safe treatment for sensitive teeth.

PMID- 29178703
TI  - Bond strength and cement-tooth interfacial characterization of self-adhesive
      composite cements.
AB  - PURPOSE: (1) To determine the microtensile bond strength (uTBS) of self-adhesive
      (SA) composite cements to unetched/etched enamel and dentin, and (2) to
      characterize the cements' interaction with tooth tissue. METHODS: 51 composite
      blocks were bonded to smear layer-covered enamel and dentin (three teeth per
      group). Four SA composite cements (Clearfil SA, G-CEM, RelyX Unicem, SmartCem2),
      and three multi-step composite cements, two used following an etch-and-rinse
      (E&R) approach (RelyX ARC, Variolink II 'E&R') and one used following a self-etch
      (SE) approach (Variolink II ' SE') were investigated. The cement-tooth specimens
      were perpendicularly sectioned into micro-specimens (1.0 * 1.0 mm) in order to
      measure the uTBS. The data were statistically analyzed by ANOVA followed by Tukey
      HSD (P< 0.05). 24 additional specimens (four teeth per group) were prepared for
      interfacial characterization using SEM. RESULTS: The tested SA cements bonded
      equally well to enamel and dentin. Etching of enamel improved their bonding
      effectiveness, which however remained inferior to that of both E&R cements. SEM
      revealed a very similar interfacial ultrastructure at smear layer-covered enamel
      and dentin for the SA cements, exhibiting very superficial interaction at enamel
      and absence of a clearly detectable hybrid layer and resin tags in the dentin
      tubules. When the SA composite cements were applied to dentin free of a smear
      layer, regular and long resin tags were formed. CLINICAL SIGNIFICANCE: No
      significant differences in bonding effectiveness were recorded for the self
      adhesive composite cements when bonded to unetched/etched enamel and to dentin.
      Multi-step etch-and-rinse composite cements showed a better bonding effectiveness
      to enamel, although this could be approximated by the self-adhesive composite
      cements when enamel was acid-etched beforehand. On dentin, however, the bond
      strength of the etch-and-rinse composite cement RelyX ARC was superior.

PMID- 29178704
TI  - Occlusal stress is involved in the formation of non-carious cervical lesions. A
      systematic review of abfraction.
AB  - PURPOSE: This systematic review on abfraction studied whether stress is a
      mechanism in the formation of non-carious cervical lesions (NCCLs). METHODS: A
      literature search was performed on three electronic databases (PubMed, ISI Web of
      Science, and EMBASE) using the keyword "abfraction" in publications published in
      English. The inclusion criteria were clinical and laboratory studies that
      investigated the role of abfraction in NCCLs. The title and abstract of the
      identified publications were screened by two investigators independently.
      Reviews, case reports, and irrelevant papers were excluded. Full text of the
      remaining publications were retrieved. A manual search was performed on the
      bibliographies of the selected publications to identify additional relevant
      publications for review. RESULTS: A total of 372 publications were identified,
      and 165 duplicated publications and 166 irrelevant publications were excluded.
      From the bibliographies of the remaining 41 publications, 28 relevant
      publications were found. Therefore, 69 publications (31 clinical studies and 38
      laboratory studies) were included in this review and the majority (56/69, 81%)
      found an association between occlusal stress and NCCLs. Although no clinical
      study demonstrated that NCCL was caused by stress alone, 23 studies reported that
      stress or occlusal factors were associated with NCCLs. Of the 38 laboratory
      studies, 24 that used finite element analysis found that stress was concentrated
      at the cervical region of the tooth. Nine laboratory studies suggested that
      stress was a mechanism for NCCLs, whereas five studies reported the opposite. In
      conclusion, current literature supported an association between occlusal stress
      and NCCLs. CLINICAL SIGNIFICANCE: This systematic review of abfraction found the
      majority of studies reported an association between occlusal stress and non
      carious cervical lesions.

PMID- 29178705
TI  - Effectiveness of dentifrices with new formulations for the treatment of dentin
      hypersensitivity - A meta-analysis.
AB  - PURPOSE: This meta-analysis was conducted to evaluate if strontium-acetate- and
      arginine-containing dentifrices can significantly reduce dentin hypersensitivity
      (DH). METHODS: A systematic literature search was performed. The investigation
      period was from 2006 to 2015 with the search term "dentin hypersensitivity". Nine
      original articles were relevant. A network meta-analysis of combined z scores was
      performed. Pooled results from random effects models with their 95% confidence
      intervals are reported. RESULTS: The results from the random effects network meta
      analysis show a significant improvement for the agents strontium acetate,
      arginine, and arginine with whitener, at all times for all stimuli, in comparison
      with the placebo. Strontium chloride is equivalent to the placebo. None of the
      dentifrices had a negative effect on DH. This meta-analysis showed that strontium
      acetate- and arginine-containing dentifrices can significantly reduce DH. Calcium
      sodium silicate and potassium nitrate formulas show a tendency for pain relief.
      Because of the limited power of the available studies, a randomized study with
      several agents is recommended. CLINICAL SIGNIFICANCE: The aim of the treatment of
      dentin hypersensitivity (DH) is pain relief. Dentifrices with formulations of
      strontium acetate, of arginine or of arginine with whitener seem to have a good
      impact in the therapy of DH and can be recommended for daily use.

PMID- 29178706
TI  - Stress distribution of bulk-fill resin composite in class II restorations.
AB  - PURPOSE: To study the influence of the resin bonding layer thickness and the bulk
      filling material stiffness in adhesive class II mesio-occlusal-distal (MOD)
      restorations using numerical finite element analysis (FEA). METHODS: Four 3D-FE
      models of teeth restored with different filling material stiffness and resin
      bonding layer thickness were built-up and analyzed. The 3D model of a sound lower
      molar was also analyzed and compared with restored ones. The tooth tissues
      (enamel, dentin), dental restoration and bolus on the occlusal surface, was
      divided into 3D solid CTETRA elements with four grid points. The adhesive bonding
      around the dental restoration was modeled with shell elements. Polymerization
      shrinkage was simulated with a thermal expansion approach. Mechanical behavior of
      restored models in terms of stress and displacement distributions, under the
      combination effects of polymerization shrinkage and occlusal load (600 N), was
      analyzed. All the materials were assumed to behave as elastic materials
      throughout the entire deformation. RESULTS: Numerical results show that the
      mechanical response of the restored models was very different compared to the
      sound tooth ones, where the stress was uniformly distributed from enamel to
      dentin with no critical stress concentration. In the restored models, the highest
      stress values were detected in the enamel, near the enamel-dentin interface and
      in the bulk restorative material. Tooth preparations A and B showed lower
      gradient stresses than corresponding C and D. The value of the vertical
      displacement components in models A and B were higher than corresponding C and D.
      The maximum displacement values were mainly located around the groove and were
      higher by an order of magnitude than the sound models. The results showed better
      mechanical response with models A and B compared to C and D. It is also evident
      that resin bonding thickness slightly affected the stress level of the restored
      teeth. CLINICAL SIGNIFICANCE: Class II MOD direct bulk resin composite
      restorations showed a high susceptibility to damage at the marginal and internal
      tissue interfaces depending on their own stiffness. The use of resin-based bulk
      filling materials is not recommended for large class II MOD adhesive restorations
      due to mechanical behavior failure risk.

PMID- 29178707
TI  - Effect of CAD/CAM glass fiber post-core on cement micromorphology and fracture
      resistance of endodontically treated roots.
AB  - PURPOSE: To investigate the fracture resistance of weakened roots restored with
      prefabricated or CAD/CAM-customized posts and cores as well as the thickness of
      the cement film and the presence of voids in the cement. METHODS: The roots of 40
      human premolars were weakened by removing internal dentin with a diamond bur (2.5
      mm in the coronal third and 1.5 mm in the apical third) and restored with
      prefabricated posts (PPs) or customized posts (CPs) with or without a zirconia
      crown (n= 10). Posts and crowns were cemented with resin cement. Microtomography
      was used to determine the thickness of the cement film and whether voids were
      present. After fatigue testing (1 million cycles, 50 N, 5 Hz, 36.5 degrees C),
      the specimens underwent compression testing with an oblique load (30 degrees , 1
      mm/minute) and fracture strengths were recorded (N). Fracture strength and film
      thickness were analyzed with ANOVA and the Games-Howell test; the variable
      presence of voids was analyzed with the Mann-Whitney test (alpha= 5%). RESULTS:
      Mean fracture strengths varied between 640.4 and 792.9 N and did not differ
      significantly between groups. The CP group had a thinner cement film and fewer
      voids than the PP group. There was a positive, statistically significant
      correlation (Spearman, R=0.488, P= 0.029) between these variables. CLINICAL
      SIGNIFICANCE: CAD/CAM-manufactured glass-fiber posts and cores do not affect the
      fracture strength of flared root canals or cause catastrophic failure of the root
      when used with zirconia crowns.

PMID- 29178708
TI  - Influence of extremely high irradiances on the micromechanical properties of a
      nano hybrid resin based composite.
AB  - PURPOSE: To investigate in vitro the effect of extremely high irradiance light
      emitting diode (LED) light curing units (LCU) with different exposure distances
      and curing modes on the micromechanical properties of a nano hybrid resin based
      composite. METHODS: 72 resin based composite (RBC) (Kalore) specimens with 2 mm
      thickness were cured using two high irradiance LED LCUs (Bluephase 20i and
      FlashMax P3) at 0 and 7 mm exposure distances. The curing conditions were:a)
      Bluephase 20i - 10 seconds - High power; b) Bluephase 20i - 15 seconds - High
      power; c) Bluephase 20i - 5 seconds - Turbo; d) Bluephase 20i - 15 seconds - Soft
      start; e) FlashMax P3 - 4 mm tip cover - 3 seconds; f) FlashMax P3 - without tip
      cover - 3 seconds. The incident and transmitted irradiance and radiant exposure
      were evaluated in real time during curing, with a radiometer (MARC Resin
      Calibrator). The micromechanical properties (Vickers hardness, HV and indentation
      modulus, E) were measured with an automatic universal hardness indenter after
      storing specimens for 24 hours in distilled water. Data were analyzed with one-
      and two-way ANOVA tests followed by Tukey test and partial eta-square statistics
      (alpha= 0.05). RESULTS: For both LCUs, incident irradiance decreased
      progressively with increased exposure distance, reaching at 7 mm exposure
      distance less than 50% of the value measured when the LCU was applied directly on
      specimen's surface. In descending order of strength of their effects, the
      parameters incident irradiance (HV; eta P2 =0.828, E; 0.693), LCU (HV, 0.257, E,
      0.043) and exposure distance (HV, 0.031, E, 0.028) were significant factors
      affecting HV and E (P < 0.05). The localized radiant exposure (the incident and
      transmitted) as well as the position of HV and E measurements (top-bottom of the
      specimen) were additional factors affecting significantly only HV (P < 0.05), but
      not E (P > 0.05). CLINICAL SIGNIFICANCE: Extremely high irradiances were less
      efficient in adequate curing of the analyzed nano hybrid composite. Using a
      protection tip, as clinically indicated, reduces the irradiance of FlashMax P3
      from 7,681.7 (160.53) mW/cm2; to 3052.5 (71.61) mW/cm2;.

PMID- 29178709
TI  - Determination of polymerization shrinkage of different composites using a
      photoelastic method.
AB  - PURPOSE: To investigate the polymerization shrinkage stress of different low
      viscous bulk composites (SDR, Venus Bulk Fill, X-tra Base, Filtek Bulk Fill) in
      comparison to a conventional flowable composite (Filtek Supreme XTE Flow) and to
      high viscous bulk and conventional composites (Filtek Supreme XTE, GrandioSO,
      Tetric EvoCeram, Tetric EvoCeram BulkFill, Venus Diamond, Venus Pearl), as well
      as to an experimental composite (Ormocer) and a sonic-activated bulk fill
      composite (Sonicfill), by means of photoelastic investigation. METHODS: To ensure
      bonding of the resin composite, cylindrical cavities (O 4mm) in araldite B
      epoxide resin plates (40 * 40 * 4 mm3) were pre-treated with the Rocatec system.
      Embedded in araldite plates, six resin composite specimens of each material were
      exposed for 60 seconds from one side (Translux Power Blue, 1,000 mW/cm2). The
      samples were stored, light-protected and dry (23 degrees C). Polymerization
      shrinkage stress data (MPa) were calculated 15 minutes, 1 and 24 hours after
      light exposure, based on the diameter of the isochromatic curves of first order,
      obtained from araldite plates. Statistical analysis was performed with the
      Wilcoxon-test and Bonferroni correction (P< 0.0006). RESULTS: After 15 minutes/1
      hour, the mean polymerization stress values calculated were:for SDR 4.4 +/-
      0.1/4.4 +/- 0.2 MPa; Venus Bulk Fill 4.8 +/- 0.3/4.9 +/- 0.3 MPa; X-tra Base 6.5
      +/- 0.3/6.7 +/- 0.3 MPa; Filtek Bulk Fill 4.9 +/- 0.3/4.9 +/- 0.3 MPa; Filtek
      Supreme XTE Flow 8.0 +/- 0.3/8.2 +/- 0.2 MPa; Filtek Supreme XTE 7.1 +/- 0.1/7.4
      +/- 0.2 MPa; GrandioSO 6.3 +/- 0.4/6.3 +/- 0.3 MPa; Tetric EvoCeram 4.5 +/-
      0.1/4.6 +/- 0.1 MPa; Tetric EvoCeram BulkFill 4.9 +/- 0.2/5.0 +/- 0.3 MPa; Venus
      Diamond 3.7 +/- 0.3/3.8 +/- 0.3 MPa; Venus Pearl 3.9 +/- 0.2/4.0 +/- 0.2 MPa,
      Sonicfill 5.4 +/- 0.2/5.6 +/- 0.3 MPa; and Ormocer (experimental) 4.1 +/- 0.2/4.3
      +/- 0.2 MPa. After 24 hours, the following mean stress values were obtained:SDR
      4.7 +/- 0.2 MPa; Venus Bulk Fill 5.1 +/- 0.2 MPa; X-tra Base 7.2 +/- 0.4 MPa;
      Filtek Bulk Fill 5.3 +/- 0.3 MPa; Filtek Supreme XTE Flow 8.7 +/- 0.3 MPa; Filtek
      Supreme XTE 7.9 +/- 0.2 MPa; GrandioSO 7.0 +/- 0.4 MPa; Tetric EvoCeram 4.9 +/-
      0.1 MPa; Tetric EvoCeram BulkFill 5.4 +/- 0.3 MPa; Venus Diamond 4.5 +/- 0.3 MPa;
      Venus Pearl 4.5 +/- 0.3 MPa, Sonicfill 5.8 +/- 0.2 MPa and Ormocer (experimental)
      4.5 +/- 0.2 MPa. The new and experimental resin composites showed significantly
      less polymerization shrinkage stress than the conventional resin composite
      (Filtek Supreme XTE). CLINICAL SIGNIFICANCE: Resin composite restoratives differ
      in their polymerization shrinkage stress development, independent of their
      viscosity. Some low viscosity bulkfill-restoratives generate less shrinkage
      stress compared to other conventional or bulk-restoratives. Practitioners should
      yield to the potential effect of shrinkage stress development, because this might
      affect marginal integrity in the clinical performance.

PMID- 29178710
TI  - Effect of conventional and contemporary disinfectant techniques on three peri
      implantitis associated microbiotas.
AB  - PURPOSE: To evaluate the antiseptic properties of five different disinfectant
      techniques on three different peri-implantitis (PI) associated biofilms. METHODS:
      90 implant titanium disks, with the same thickness and diameter, were prepared
      and randomly divided into 18 groups (n = 5) based on the microbiota strains (S.
      aureus, S. epidermidis and C. albicans) and using the following disinfectant
      techniques:soft laser therapy, photodynamic therapy (PDT), 0.12% NaOCl, 0.2%
      chlorhexidine, 3% H2O2, and control groups. After forming a protein layer on disk
      surfaces, the specimens were exposed to the microbial suspensions. After
      decontamination according to designated techniques, 2% Trypsin protease was
      administered to isolate the surviving microorganisms. Muller Hinton agar culture
      was used for microbiota growth. After 48-hour incubation, the standard colony
      forming unit (CFU) was assayed and the collected data were analyzed by Kruskal
      Wallis and Mann-Whitney tests at a significance level of 0.05. RESULTS: The
      highest amount of CFU/ml values was shown by C. albicans, which was subjected to
      PDT (25.12 +/- 30.23). The least disinfecting efficacy on S. epidermidis was
      demonstrated by the laser group (all P-values <= 0.01). Nevertheless, all of the
      groups exhibited significant differences with the control groups (all P-values <
      0.01). CLINICAL SIGNIFICANCE: None of the studied disinfectant techniques had the
      highest lethal effects on all of the tested microbiotas. Therefore, a combination
      of these disinfectant techniques, for instance PDT + 3% H2O2 or 0.2%
      chlorhexidine, is recommended.

PMID- 29178711
TI  - Efficacy of an experimental 3% potassium nitrate mouthwash in providing long-term
      relief from dentin hypersensitivity:An 8-week randomized controlled study (Study
      1).
AB  - PURPOSE: To evaluate the efficacy of an experimental mouthwash containing 3%
      potassium nitrate (KNO3) in relieving dentin hypersensitivity when used as an
      adjunct to brushing with fluoride toothpaste compared with use of the same
      toothpaste alone. METHODS: This was one of three randomized, two-treatment,
      examiner-blind, parallel-design, single-site, 8-week studies in healthy subjects
      with self-reported and clinically diagnosed dentin hypersensitivity. Subjects
      were randomized to receive either fluoride toothpaste plus 3% KNO3 mouthwash or
      the same fluoride toothpaste alone, and instructed to use their allocated
      treatment twice daily for the next 8 weeks. Dentin hypersensitivity was evaluated
      at baseline and following 4 and 8 weeks of treatment through assessment of
      responses to evaporative (air) and tactile stimuli [measured by the Schiff
      Sensitivity Scale, a visual rating scale (VRS), and tactile threshold,
      respectively], and using the Dentin Hypersensitivity Experience Questionnaire
      (DHEQ; a validated quality-of-life instrument for dentin hypersensitivity).
      RESULTS: A total of 216 subjects were randomized and 214 completed the study.
      Both treatment groups demonstrated statistically significant reductions from
      baseline for each clinical measure of sensitivity (P<= 0.01) at Weeks 4 and 8.
      Use of the 3% KNO3 mouthwash after brushing with fluoride toothpaste resulted in
      statistically significantly greater reductions in sensitivity to an evaporative
      (air) stimulus (mean Schiff score and mean VRS, P< 0.001; primary objective mean
      Schiff score at Week 8, P< 0.0001) and statistically significantly higher tactile
      threshold (P< 0.001) at Weeks 4 and 8 compared with toothpaste alone. The DHEQ
      responses reflected the clinical outcomes for several parameters, indicating a
      significant improvement in oral health-related quality of life after 8 weeks' use
      of the 3% KNO3 mouthwash. CLINICAL SIGNIFICANCE: The results of this study
      suggest that daily use of a 3% KNO3 mouthwash as an adjunct to brushing with
      fluoride toothpaste provides clinically relevant improvements in dentin
      hypersensitivity after 8 weeks' twice-daily use.

PMID- 29178712
TI  - Role of tyrosol on Candida albicans, Candida glabrata and Streptococcus mutans
      biofilms developed on different surfaces.
AB  - PURPOSE: To assess the effect of tyrosol on the production of hydrolytic enzymes
      (by Candida biofilm cells) and acid (by Streptococcus mutans biofilms), as well
      as to quantify single and mixed biofilms of these species formed on acrylic resin
      (AR) and hydroxyapatite (HA). METHODS: Candida and S. mutans biofilms were formed
      on AR and HA in the presence of tyrosol during 48 hours. Next, acid proteinase,
      phospholipase and hemolytic activities of Candida biofilm cells were determined,
      while acid production by S. mutans biofilms was assessed by pH determination. The
      effect of tyrosol on mature biofilms (96 hours) was evaluated through
      quantification of total biomass, metabolic activity, number of colony-forming
      units and composition of biofilms' extracellular matrix. Data were analyzed by
      one- and two-way ANOVA, followed by Tukey's and Holm-Sidak's tests (alpha =
      0.05). RESULTS: Treatments with tyrosol were not able to significantly reduce
      hydrolytic enzymes and acid production by Candida and S. mutans. Tyrosol only
      significantly reduced the metabolic activity of single biofilms of Candida
      species. CLINICAL SIGNIFICANCE: Tyrosol on its own had a limited efficacy against
      single and mixed-species oral biofilms. Its use as an alternative antimicrobial
      for topical therapies still demands more investigation.

PMID- 29178713
TI  - Influence of manual and power toothbrushes on clinical and microbiological
      findings in initial treatment of periodontitis - A randomized clinical study.
AB  - PURPOSE: This randomized clinical study compared the influence of manual and
      power toothbrushes on clinical and microbiological findings in initial treatment
      of periodontitis. METHODS: A total of 72 participants with a mean age of 55.7
      years were randomly assigned to three groups (n= 24):oscillating-rotating (OR),
      sonic-active (SA) and manual toothbrush (MTB). At baseline, after 4 weeks and
      after 12 weeks, the following parameters were assessed:modified Quigley-Hein
      Index (QHI), papilla bleeding index (PBI), periodontal pocket depth (PPD),
      bleeding on probing (BOP) and recession. For microbiological analysis (PCR) of 11
      periodontal pathogenic bacteria, samples of sulcular fluid were taken from the
      deepest pockets. Statistical analysis was performed using ANOVA, with the level
      of significance set at alpha= 5%. RESULTS: All clinical parameters:PBI, modified
      QHI, PPD, BOP and recession showed an improvement after 12 weeks compared to
      baseline, regardless of which toothbrush system was used. Regarding PBI, the SA
      group showed significantly greater improvement compared to OR and MTB (P< 0.01).
      In plaque removal (QHI) only OR was significantly more effective than MTB (P=
      0.01). Periodontal parameters showed a significantly higher reduction of PPD for
      SA compared to MTB and MTB compared to OR (Plt; 0.05), while for BOP only a
      significantly higher reduction in SA compared to OR was detected (P= 0.01)
      Microbiological analysis showed an improvement in prevalence of several bacteria
      without significant differences between groups. CLINICAL SIGNIFICANCE: Patients
      might benefit from powered TB systems, especially in initial treatment of
      periodontitis.

PMID- 29178714
TI  - Fluoride release and re-release from various esthetic restorative materials.
AB  - PURPOSE: To measure the amount of fluoride release and re-release after re-charge
      from two commonly used esthetic restorative materials and compare it to a new
      experimental material. METHODS: 30 standardized disc-shaped specimens were
      fabricated using resin-based composite (Z100), resin-modified glass-ionomer
      cement (Vitremer) and a new experimental material which is a self-curing resin
      based composite with light curing option. 10 specimens were made from each
      material. The specimens of each group were immersed separately in 10 ml distilled
      water. Fluoride release was measured after 1, 7, 14 and 30 days using a fluoride
      specific ion electrode and an ion-analyzer. The specimens were then exposed to
      2.0% neutral sodium fluoride foam (0.9% fluoride ion). The amount of fluoride re
      released was measured at Days 1, 7, 14 and 30. RESULTS: An ANOVA indicated a
      statically significant variance among the groups (P< 0.001). The experimental
      group demonstrated significantly less fluoride release at Day 1 compared to Day
      31 (first day after 2% sodium fluoride application). At Days 7, 14 and 30 there
      was significantly more fluoride release than Day 7, 14 and 30 after the topical
      fluoride application (P< 0.001). There was significantly more fluoride release
      from Vitremer than the experimental material at Days 1 and 7. However, similar
      release was observed at Days 14 and 30 for Vitremer and experimental material,
      but not for Z100. Both Vitremer and the experimental material showed
      significantly more release of fluoride compared to Z100 at all time points.
      CLINICAL SIGNIFICANCE: This study demonstrates that the new experimental material
      released fluoride, re-charged and re-released fluoride at a level comparable to
      Vitremer but more than Z100.

PMID- 29178715
TI  - Effects of atmospheric non-thermal argon/oxygen plasma on biofilm viability and
      hydrophobicity of oral bacteria.
AB  - PURPOSE: To evaluate the bactericidal effects of atmospheric non-thermal
      argon/oxygen plasma on in vitro oral biofilms constructed from S. mutans and/or
      S. sanguinis, and the influence of the plasma on the virulence properties of A.
      oris. METHODS: In vitro oral biofilms were constructed in the wells of 48-well
      plates from S. mutans and/or S. sanguinis. The wells containing constructed
      biofilms and various amounts of phosphate-buffered saline (PBS) were treated with
      non-thermal argon/oxygen plasma brush for 2 minutes. The methylthiazolyldiphenyl
      tetrazolium bromide (MTT) assay and Live/Dead assay were used to evaluate the
      viability of biofilms in those wells after the plasma treatments. Meanwhile, A.
      oris suspensions were treated with the plasma and then evaluated for their
      virulence properties by measuring the hydrophobicity and co-aggregation
      capability of treated A. oris. RESULTS: The MTT assay showed that exposure to non
      thermal plasma for 2 minutes significantly reduced the viability of bacteria in
      both single-species and two-species biofilms of S. mutans and S. sanguinis with
      the reductions of up to 99%. Meanwhile, plasma treatment also altered the
      hydrophobicity of A. oris, and reduced their capability to co-aggregate with S.
      sanguinis. CLINICAL SIGNIFICANCE: The results from this study demonstrated that
      atmospheric non-thermal argon/oxygen plasma could effectively deactivate oral
      bacteria biofilm by decreasing bacterial viability as well as reducing their
      hydrophobicity and co-aggregation capability.

PMID- 29178716
TI  - Clinical evaluation of a toothpaste containing lysozyme for the treatment of
      recurrent aphthous stomatitis: A 3-month, double-blind, randomized study.
AB  - PURPOSE: To assess the efficacy and safety of a toothpaste containing lysozyme
      for the treatment of minor recurrent aphthous stomatitis (MiRAS) in a 3-month
      clinical trial. METHODS: 71 participants with MiRAS were recruited to this
      randomized, parallel-controlled, double-blind clinical trial. Participants were
      allocated randomly to the test group or the control group. Demographic data and
      pain score (visual analogue scale, VAS) were recorded at baseline. Healing time
      of MiRAS, recurrence frequency and side effects were recorded at the 1-, 2- and 3
      month follow-up visits. All data were analyzed using SAS software version 8.0.
      RESULTS: There was no significant difference (P>0.05) in pain score between the
      treatment group (3.00 +/- 1.66) and the control group (2.66 +/- 1.51). The
      average healing time was significantly reduced (P< 0.01) in the treatment group
      (5.66 +/- 2.02) compared with the control group (7.46 +/- 2.69), while the
      recurrence frequency also showed a significant reduction from 4.40 +/- 2.89 in
      the control group to 3.06 +/- 1.48 in the treatment group (P< 0.05). No obvious
      side effects were observed. CLINICAL SIGNIFICANCE: The results of this clinical
      study supported the conclusion that a toothpaste containing lysozyme was
      effective in promoting healing and reducing recurrence frequency without
      significant side effects in the treatment of minor recurrent aphthous stomatitis.

PMID- 29178717
TI  - The influence of the utilization time of brush heads from different types of
      power toothbrushes on oral hygiene assessed over a 6-month observation period: A
      randomized clinical trial.
AB  - PURPOSE: This randomized clinical trial investigated the influence of the
      utilization time of brush heads from different types of power toothbrushes
      [oscillating rotating (OR) and sonic action (SA)93; on oral hygiene (plaque
      accumulation and gingival inflammation) over a 6-month observation period.
      METHODS: 49 participants were randomly allocated into two groups: use of the same
      brush head over 6 months (NR: non-replacement) or replacement of brush head every
      4 weeks over 6 months (R: replacement). Each group was subdivided into two
      subgroups according to kind of toothbrush (TB) used (OR and SA). Modified Quigley
      Hein plaque index (QHI), papilla bleeding index (PBI), and gingival index (GI)
      were recorded at baseline and 2, 8, 12, 16, and 24 weeks after baseline. After 24
      weeks, participants of both groups (R and NR) received a new brush head. At week
      26, final QHI, PBI, and GI were recorded. RESULTS: QHI decreased between baseline
      and follow-up visits in R groups (P< 0.05), with the exception of week 12 (P=
      0.26). In NR groups, no significant decrease was detected (P> 0.05). There was no
      significant effect of time on PBI or GI in any of R subgroups (P> 0.05). In NR
      oscillating/rotating TB: significant increase in PBI and GI was detected 24 weeks
      after baseline (PBI: P= 0.02, GI: P= 0.03); sonic action TBs showed significant
      decrease in PBI at every follow-up visit (P< 0.05), except at 24 weeks after
      baseline (P= 0.73). GI was significantly decreased at 2 weeks after baseline only
      (P< 0.01). CLINICAL SIGNIFICANCE: Six-month use of the same brush head reduced
      effectiveness in removing plaque, and gingival inflammation appeared to increase
      after a utilization time of over 4 months. Replacing brush heads is advised after
      4 months.

PMID- 29178718
TI  - Antimicrobial and antibiofilm activity of silver, titanium dioxide and iron nano
      particles.
AB  - PURPOSE: To compare the antimicrobial effects of chlorhexidine, penicillin,
      erythromycin, clindamycin, tetracycline and vancomycin with silver, titanium
      dioxide and iron nanoparticles and also to consider the synergistic antibacterial
      and antibiofilm effects of nanoparticles in clinical and standard strains of
      Streptococcus mutans and Streptococcus sanguinis. METHODS: The specimens
      collected from 66 3-5 year-old children with detected S. mutans and S. sanguinis
      by PCR were then exposed to the antimicrobial activity of chlorhexidine,
      penicillin, erythromycin, clindamycin, tetracycline and vancomycin with silver,
      titanium dioxide and iron nanoparticles measured by microdilution and disc
      diffusion tests and the colony counted after 1 to 5 minutes. The antibiofilm
      activity was examined by microtiter test. RESULTS: Use of nanoparticles alone
      showed higher minimum inhibitory concentration (MIC) than using them
      synergistically. The most effective synergistic solution was the one containing
      TiO2, Ag and Fe3O4 showing 0.019 MUg#47;ml in S. mutans and S. sanguinis.
      Furthermore, this solution had the lowest biofilm inhibitory concentration (BIC)
      and colony forming units than the other antibiotics and chlorhexidine. CLINICAL
      SIGNIFICANCE: The solution containing TiO2, Ag and Fe33O4 showed the lowest
      inhibitory and antibiofilm concentration against S. mutans and S. sanguinis
      compared to those of other nanoparticle containing solutions, antibiotics and
      chlorhexidine, thus it may be used for treating dental caries, dental plaque and
      oral infections.

PMID- 29178719
TI  - Quantitation of endotoxin and lipoteichoic acid virulence using toll receptor
      reporter gene.
AB  - PURPOSE: To apply quantitative Toll-like receptors (TLR) cell assays to compare
      lipopolysaccharides (LPSs) and lipoteichoic acids (LTAs) from different oral
      bacterial strains for potential pathogenicity in vitro. METHODS: The potency of
      LPS and LTA from different bacteria on activation of TLR reporter genes in HEK
      tlr cell lines was examined. P. gingivalis LPS mix, P. gingivalis 1690 LPS, P.
      gingivalis 1435/50 LPS, E. coli LPS (E. coli K12), B. subtilis LTA, S. aureus
      LTA, E. hirae LTA and S. pyogenes LTA were examined in both TLR2 and TLR4 HEK
      cell line reporter assays. Solutions of LPS and LTA from selected bacteria were
      applied in a dose response fashion to the TLR reporter cells under standard
      culture conditions for mammalian cells. Reporter gene secreted-embryonic-alkaline
      phosphatase (SEAP) was measured, and half maximal effective concentration (EC50)
      was determined for each sample. Concentration dependent TLR activation was
      compared to similar responses to LPS and LTA for commercial BODIPY-TR-Cadaverine
      and LAL biochemical (non cell based) assays. RESULTS: All LPS from P. gingivalis
      activated both TLR2 and TLR4 responses. E. coli LPS is a strong activator for
      TLR4 but not for TLR2 responses. In contrast, both B. subtilis and S. aureus LTA
      provoked responses only in TLR2, but not in the TLR4 assay. Interestingly, E.
      hirae LTA and S. pyogenes LTA did not stimulate strong TLR2 responses. Instead,
      both E. hirae LTA and S. pyogenes LTA mounted a reasonable response in TLR4
      reporter gene assay. Both LPS and LTA showed deactivation of fluorescence in
      BODIPY-TR-Cadaverine while only LPS was active in LAL. As with biochemical
      assays, an EC50 could be determined for LPS and LTA from various bacterial
      strains. The EC50 is defined as a concentration of LPS or LTA that provokes a
      response halfway between the baseline and maximum responses. Lower EC50 means
      higher potency in promoting TLR responses, and in principle indicates greater
      toxicity to the host. CLINICAL SIGNIFICANCE: InvivoGen TLR2 and TLR4 assays
      distinguish specific types of microbial products, such as LPS and LTA from
      different bacteria. Application of EC50 determinations creates a means for
      quantitative and comparisons of LPS and LTA virulence in a cellular-based assay
      and combinations of TLR reporter cell assays along with biochemical evaluation of
      LPS#47;LTA in BODIPY-TR-Cadaverine and LPS in LAL assays provides a means to
      quantitate virulence of plaque samples with respect to both LPS and LTA. These
      learnings have long-term implications for patient care in that understanding the
      virulence of patients' plaque provides important information to assess risk of
      oral diseases.

PMID- 29178720
TI  - Lipopolysaccharide and lipoteichoic acid binding by antimicrobials used in oral
      care formulations.
AB  - PURPOSE: To study the reactivity of lipopolysaccharide (LPS) and lipoteichoic
      acid (LTA) with the cationically charged agents cetylpyridinium chloride,
      stannous fluoride, and the non-cationic agent triclosan. We also assessed the
      effect of these agents to inhibit LPS and LTA binding to cellular Toll-like
      Receptors (TLRs) in vitro. METHODS: The ability of these antimicrobials to bind
      with LPS and/or LTA was assessed in both the Limulus amebocyte lysate and BODIPY
      TR-cadaverine dye assays. Mass spectroscopy was then used to confirm that
      stannous fluoride directly binds with LPS and to determine stoichiometry. Lastly,
      we looked for possible inhibitory effects of these antimicrobial agents on the
      ability of fluorescently conjugated LPS to bind to TLR4 expressed on HEK 293
      cells. RESULTS: Cetylpyridinium chloride (CPC) and stannous salts including
      stannous fluoride interfered with LPS and LTA reactivity in both dye assays,
      while triclosan had no effect. Mass spectroscopy revealed direct binding of
      stannous fluoride with E. Coli LPS at 1:1 stoichiometric ratios. In the cellular
      assay, cetylpyridinium chloride and stannous fluoride, but not triclosan,
      inhibited LPS binding to TLR4. CLINICAL SIGNIFICANCE: These results support a
      potential mechanism of action for stannous fluoride and CPC formulated in oral
      products in which these ingredients bind bacterial toxins and potentially render
      them less toxic to the host. These results may influence home care
      recommendations for patients at risk for plaque-related diseases.

PMID- 29178721
TI  - The new generation of conventional and bulk-fill composites do not reduce the
      shrinkage stress in endodontically-treated molars.
AB  - PURPOSE: To compare flowable and regular paste bulk-fill resin composites with
      old and new generation conventional composites that use incremental filling
      techniques for direct restoration of endodontically-treated teeth. METHODS: Four
      resin composites produced by the same company (3M-ESPE) were used: two
      conventional resin composites (old formulation, Z100, and new nanofilled
      formulation, Filtek Supreme XT); and two bulk-fill resin composites (flowable
      composite, Filtek Bulk-fill Flowable associated with Filtek Supreme, and regular
      paste, Filtek Bulk-fill Posterior). Elastic modulus (E), Vickers hardness (VH),
      post-gel shrinkage (Shr), diametral tensile strength (DTS) and compressive
      strength (CS) were determined (n= 10) and statistically analyzed using ANOVA and
      Tukey's test (alpha=0.05). Shrinkage stresses were analyzed using non-linear
      finite element analysis. RESULTS: Filtek Bulk-fill flowable and Filtek Supreme XT
      had higher CS than Z100 and Filtek Bulk-fill Posterior. Z100 and Filtek Supreme
      XT had higher DTS than Filtek Bulk-fill Posterior. Filtek Bulk-fill flowable had
      the lowest values and Z100 the highest E and Shr. Z100 resulted in higher
      stresses in the enamel and in root dentin close to the pulp chamber than the
      other filling techniques. Filtek Bulk-fill Flowable resulted in lower stress than
      other resin composites. CLINICAL SIGNIFICANCE: Using bulk-fill composites,
      especially flowable resin composite, created lower stresses in restored
      endodontically-treated teeth. Clinicians, when deciding for direct restoration of
      endodontically-treated teeth, may choose the bulk-fill composite to decrease
      undesirable effects of direct restoration while simplifying filling procedure.

PMID- 29178722
TI  - Case-specific finite element analysis of dental CAD/CAM prostheses to identify
      design flaws prior to manufacture.
AB  - PURPOSE: To apply a design optimization strategy to dental prostheses machining
      to verify whether this approach can detect flaws occurring in the CAD process and
      to estimate the influence of the type of material on the occurrence of fractures
      in restorations. METHODS: The stereo lithography interface format of a 4-unit
      (from canine to first molar) fixed dental prosthesis designed by a conventional
      dental CAD process was converted into a Finite Element Analysis (FEA) model. This
      basic model was coupled to the mechanical properties of feldspathic ceramic,
      lithium disilicate ceramic (LS2) and zirconia (ZrO2) to create three FEA models
      with different mechanical properties. The models were constrained along the
      abutment housing surfaces of the canine and the first molar, respectively.
      Finally, a simulated load of 50 N was applied vertically to the occlusal surface
      of the first premolar. RESULTS: The FEA showed a stress peak concentration
      between the second connectors and the second premolar. The stress peak overcame
      the ultimate tensile stresses of feldspathic and lithium disilicate ceramics;
      conversely, the ultimate tensile stress of zirconia was not overcome. A
      geometrical flaw was identified in the 4-unit fixed dental prosthesis. The flaw
      was sensitive to tensional stress and could lead to failure of the component.
      CLINICAL SIGNIFICANCE: The results of the present investigation showed the
      importance and future impact of the application of FEA in the daily practice of
      prosthodontics. A FEA-implemented CAD process would allow proper prosthetic
      volumes with correct dimensions of the framework, in order to withstand occlusal
      loads and consequently reduce mechanical failures. FEA is a useful tool to
      simplify the design of prosthetic frameworks and select esthetic ceramic
      materials with strength enough to withstand occlusal stress.

PMID- 29178723
TI  - Effects of desensitizing toothpastes on the permeability of dentin after
      different brushing times: An in vitro study.
AB  - PURPOSE: To investigate the effects of three commercially available desensitizing
      toothpastes on dentin permeability, and compare the efficacy of each product for
      reducing dentin permeability in the short term according to the frequency and
      duration of usage. METHODS: 100 dentin discs with no caries were prepared from
      freshly extracted human third molar teeth. The dentin discs were brushed with
      three desensitizing toothpastes or with a non-desensitizing toothpaste and
      distilled water, which served as control. The 100 dentin slices were randomly
      divided into two groups (n= 50): one group underwent continuous brushing (brushed
      for 3 minutes continuously), and the other group underwent discontinuous brushing
      (brushed three times, each time for 1 minute). Then, the two groups were divided
      into five subgroups (n = 10) for the five brushing applications. Dentin
      permeability was measured with a hydraulic permeability system before and after
      brushing. RESULTS: All desensitizing toothpastes reduced dentin permeability
      significantly after treatment. Sensodyne Repair and Protect (calcium sodium
      phosphosilicate) and discontinuous brushing reduced dentin permeability
      significantly compared with continuous brushing. Dentin permeability values
      showed no significant difference between the three toothpastes after 3 minutes of
      continuous brushing. When comparing the three toothpastes under discontinuous
      brushing conditions after 3 minutes, Sensodyne Repair and Protect (calcium sodium
      phosphosilicate) reduced dentin permeability significantly. CLINICAL
      SIGNIFICANCE: Sensodyne Repair and Protect (calcium sodium phosphosilicate) and
      discontinuous brushing reduced dentin permeability significantly compared with
      continuous brushing. Moreover, brushing with Sensodyne Repair and Protect
      (calcium sodium phosphosilicate) resulted in the lowest dentin permeability
      compared with those of the other two toothpastes. These results indicated that
      Sensodyne Repair and Protect may relieve dentin hypersensitivity.

PMID- 29178724
TI  - Effect of radiotherapy, adhesive systems and doxycycline on the bond strength of
      the dentin-composite interface.
AB  - PURPOSE: To investigate the effect of radiotherapy, doxycycline and adhesive
      systems on the microtensile bond strength (MUTBS) of the dentin-composite
      interface. METHODS: 60 human third molars were sectioned to expose middle dentin
      surface and distributed according to: (1) adhesive system (Adper Scotchbond MP
      and Clearfil SE Bond) applied, (2) application or not of doxycycline, and (3)
      submission to 60 Gy total radiation (2 Gy daily doses, 5 days/week for 6 weeks)
      before restoration procedure (RtRes); after restoration procedure (ResRt) or not
      submitted to radiotherapy (Control group). Specimens were tested for MUTBS and
      mode of failure were evaluated under optical microscopy. The bonding interface
      was evaluated with a scanning electron microscope (SEM). Data was submitted to
      three-way ANOVA and Tukey's test (alpha= 0.05). RESULTS: There was no significant
      difference between the MUTBS (MPa) of Adper Scotchbond MP (25.5+/-11.1) and
      Clearfil SE (27.6+/-9.1). Control (30.5+/-10.9) and ResRt (29.2+/-10.4) presented
      MUTBS significantly higher than RtRes (23.1+/-7.2). Doxycycline (21.7+/-7.6)
      significantly reduced MUTBS compared to groups without doxycycline application
      (33.6+/-8.6). Dentin cohesive failure mode was predominant for RtRes and mixed
      failure mode for ResRt. Mixed and adhesive failures were frequently observed in
      control groups. SEM showed adhesive penetration in dentin tubules in all groups,
      regardless of the radiotherapy and the application of doxycycline. The
      radiotherapy before composite restoration procedure decreased the MUTBS. No
      statistical difference was observed between the adhesive systems. The doxycycline
      reduced MUTBS regardless of the other conditions. CLINICAL SIGNIFICANCE:
      Composite restoration procedure should be done before radiotherapy, regardless of
      the adhesive system used.

PMID- 29178725
TI  - Efficacy of an anti-discoloration system (ADS) in a 0.12% chlorhexidine
      mouthwash: A triple blind, randomized clinical trial.
AB  - PURPOSE: To determine the efficacy of an anti-discoloration system (ADS) in a
      0.12% chlorhexidine (CHX) mouthwash to reduce dental discoloration. METHODS: A
      triple-blind, cross-over, randomized clinical trial was carried out in 22 healthy
      volunteers asked to perform oral rinses, twice a day for 21 days, using 0.12% CHX
      mouthwashes containing or not ADS (wash-out= 21 days). Dental discolorations were
      compared via spectroscopy (DeltaE), and direct visual examination performed by
      the dentist and volunteers themselves. At 6 months, a further visual analysis on
      clinical images was carried out by the same volunteers and ad hoc recruited
      dental practitioners. RESULTS: A slight discoloration was the most frequent
      finding, independent of the presence of ADS, while the few severe cases of
      staining were associated with CHX alone. (DeltaE values comparing dental color
      before and after treatments were similar for CHX (8.4+/-0.1) and CHX+ADS (8.6+/
      0.9) rinses. Direct visual analysis showed no staining difference between the two
      mouthwashes. Six months later, volunteers' self-evaluation of clinical pictures
      again did not detect any significant difference between treatments, while dental
      practitioners identified CHX+ADS as less discoloring (< 0.05). Slight dental
      discoloration represents the most common side-effect of 0.12% CHX mouthwash,
      independent of the presence of ADS. Severe cases are possible, but very rare and
      mainly associated with CHX alone. CLINICAL SIGNIFICANCE: There was no evidence to
      support the 0.12% chlorhexidine with anti-discoloration agent to reduce staining.

PMID- 29178726
TI  - Shear bond strength of different materials used as core build-up to ceramic.
AB  - PURPOSE: To determine the performance of a resin composite material specially
      developed for core build-ups in comparison with conventional restorative
      materials. METHODS: 90 roughened ceramic blocs were divided into three groups;
      one group (n=30) was used for the core build-up material (Gradia Core) and the
      other two groups (n=30, each) were used for two conventional restorative
      materials (Tetric EvoCeram, Compoglass F). After adhesive fixation, specimens of
      each material were subdivided in accordance with the storage conditions
      (thermocycling or water storage). Shear bond strength was measured and fracture
      behavior was analyzed. RESULTS: Gradia Core presented significantly higher shear
      bond strength values than the conventional restorative material Tetric EvoCeram,
      both after 24 hours water storage as well as after thermocycling. Compoglass F
      did not show any statistically significant differences compared to the other
      materials, independent of the storage condition. However, Compoglass F resulted
      in numerically higher shear bond values than Tetric EvoCeram, but lower shear
      bond values than Gradia Core. Within the same materials, no statistically
      significant differences occurred regarding the storage conditions. CLINICAL
      SIGNIFICANCE: The specific core build-up material provided stronger bonding
      properties when luted to feldspar ceramic than conventional restorative
      materials, making it a suitable supporting material when high-quality esthetic
      restorations are needed for restoring decayed, but vital teeth.

PMID- 29178727
TI  - Performance of CAD/CAM fabricated fiber posts in oval-shaped root canals: An in
      vitro study.
AB  - PURPOSE: To assess the push-out strength, the cement layer thickness and the
      interfacial nanoleakage of prefabricated fiber posts, CAD/CAM fiber posts and
      metal cast posts cemented into oval-shaped root canals. METHODS: Oval-shaped post
      spaces were prepared in 30 single-rooted premolars. Roots were randomly assigned
      to three groups (n=10), according to the post type to be inserted: Group 1:
      Prefabricated fiber post (D.T. Light-Post X-RO Illusion); Group 2: Cast metal
      post; Group 3: CAD/CAM-fabricated fiber post (experimental fiber blocks). In
      Group 3, post spaces were sprayed with scan powder (VITA), scanned with an inEos
      4.2 scanner, and fiber posts were milled using an inLab MC XL CAD/CAM milling
      unit. All posts were cemented using Gradia Core dual-cure resin cement in
      combination with Gradia core self-etching bond (GC). After 24 hours, the
      specimens were sectioned perpendicular to the long axis into six 1 mm-thick
      sections, which were differentiated by the root level. Sections from six roots
      per group were used to measure the cement thickness and subsequently for the thin
      slice push-out test, whereas the sections from the remaining four teeth were
      assigned to interfacial nanoleakage test. The cement thickness around the posts
      was measured in micrometers (um) on the digital images acquired with a digital
      microscope using the Digimizer software. Thin-slice push-out test was conducted
      using a universal testing machine at the crosshead speed of 0.5 mm/minute and the
      bond strength was expressed in megaPascals (MPa). The interfacial nanoleakage was
      observed under light microscope and quantified by scoring the depth of silver
      nitrate penetration along the post-cement-dentin interfaces. The obtained results
      were statistically analyzed by Kruskal-Wallis ANOVA, followed by the Dunn's
      Multiple Range test for post hoc comparisons. The level of significance was set
      at P< 0.05. RESULTS: Statistically significant differences were found among the
      groups in push-out bond strength, cement thickness and interfacial nanoleakage
      (P< 0.05). CAD/CAM-fabricated fiber posts achieved retention that was comparable
      to that of cast metal posts and significantly higher than that of prefabricated
      fiber posts. The cement layer thickness around CAD/CAM-fabricated fiber posts was
      significantly lower than around prefabricated fiber posts, but higher than that
      around cast metal posts. Root level was not a significant factor for push-out
      strength in any of the groups, whereas it significantly affected cement layer
      thickness only in the prefabricated fiber post group. No differences were
      observed in interfacial nanoleakage between CAD/CAM fabricated and prefabricated
      fiber posts, while nanoleakage recorded in cast metal posts was significantly
      lower. CLINICAL SIGNIFICANCE: CAD/CAM fabricated fiber posts could represent a
      valid alternative to traditionally used posts in the restoration of
      endodontically-treated teeth with oval or wide root canals, offering the
      advantages of better esthetics, retention, and cement thickness values that are
      comparable to cast post and cores.

PMID- 29178728
TI  - A randomized clinical study to evaluate the effect of an ultra-low abrasivity
      dentifrice on extrinsic dental stain.
AB  - PURPOSE: To investigate the stain-removal efficacy of an experimental ultra-low
      abrasivity anti-sensitivity dentifrice containing sodium tripolyphosphate (STP)
      and a cocamidopropyl betaine/sodium methyl cocoyl taurate detergent system.
      METHODS: This was a single-center, examiner-blind, randomized, parallel-group
      study. Extrinsic dental stain was assessed on the facial surfaces of the six
      maxillary and six mandibular anterior teeth and the lingual surfaces of the six
      mandibular anterior teeth using the Macpherson modification of the Lobene Stain
      Index (MLSI). Treatments were: ultra-low abrasivity dentifrice [5% w/w KNO3, 5%
      w/w STP, 1,100 ppm fluoride as sodium fluoride; relative dentin abrasivity (RDA)
      ~10; n=54]; moderate abrasivity fluoride dentifrice (1,100 ppm fluoride as sodium
      monofluorophosphate; RDA ~68; n= 57); higher abrasivity daily-use whitening
      dentifrice (1,100 ppm fluoride as sodium fluoride; RDA~137; n= 57). Subjects
      brushed for 1 minute, twice daily, for 8 weeks. RESULTS: Mean total MLSI [ Area *
      Intensity (A*I) ] change from baseline score at Weeks 4 and 8 was significant (P<
      0.0001) for all groups. At Week 8, for the ultra-low abrasivity dentifrice versus
      the moderate and higher abrasivity dentifrices, mean total MLSI (A*I) scores (P<
      0.0001), along with MLSI endpoints in facial, lingual, and interproximal regions
      (P= 0.0035 to P< 0.0001), favored the ultra-low abrasivity dentifrice.
      Dentifrices were generally well-tolerated. The ultra-low abrasivity dentifrice
      containing 5% STP reduced extrinsic dental stain more effectively than moderate
      or higher abrasivity dentifrices. CLINICAL SIGNIFICANCE: The ultra-low
      abrasivity, anti-sensitivity dentifrice containing 5% STP reduced extrinsic
      dental stain more effectively than moderate or higher abrasivity dentifrices, and
      is thus suitable for patients with sensitive teeth who wish to control extrinsic
      dental stain.

PMID- 29178729
TI  - Surface properties and color stability of incrementally-filled and bulk-fill
      composites after in vitro toothbrushing.
AB  - PURPOSE: To evaluate the effect of simulated toothbrush abrasion on the surface
      gloss, the surface roughness and the color stability of incrementally-filled and
      bulk-fill composites. METHODS: 48 dimensionally standardized composite specimens
      (n= 8/group) were made from four incrementally-filled composites (Tetric
      EvoCeram, IPS Empress Direct Enamel, Ceram X mono and Arabesk) and two bulk-fill
      composites (Quix fil and Tetric EvoCeram Bulk). Before and after toothbrushing
      simulation the surface gloss was measured by a glossmeter, the surface roughness
      was evaluated with a profilometer, and the color was measured using a
      spectrophotometer. RESULTS: Before and after the toothbrush abrasion, IPS Empress
      Direct Enamel yielded the highest gloss value, while Ceram X mono exhibited the
      lowest gloss value. Quix fil showed the highest Ra value before the toothbrushing
      simulation, however, it showed similar Ra value with Ceram X mono and Arabesk
      after the toothbrushing simulation. IPS Empress Direct Enamel showed the lowest
      DeltaE after the simulated toothbrushing. Tetric EvoCeram Bulk showed similar
      gloss value, Ra value, and DeltaE to Tetric EvoCeram after the toothbrushing
      simulation. Simple regression analysis showed no correlation between the
      roughness and the gloss, but it showed a positive linear relationship between
      DeltaE and DeltaRa. (R2= 0.863, P= 0.027). CLINICAL SIGNIFICANCE: The evaluated
      bulk-fill composites did not exhibit significantly worse surface properties and
      color stability than incrementally-filled materials after toothbrush abrasion.
      Color changes of composites caused by toothbrush abrasion were acceptable on the
      premise that 3.3DeltaE units were considered as acceptable threshold values.

PMID- 29178730
TI  - A clinical, randomized, double-blind study on the use of toothpastes immediately
      after at-home tooth bleaching.
AB  - PURPOSE: To evaluate the effect of 5% potassium nitrate containing 2% sodium
      fluoride and 10% strontium chloride on tooth sensitivity and color change after
      at-home bleaching treatment across 3 months of follow-up. METHODS: 60 subjects
      were randomly allocated by numerical draw into three groups (n= 20): (1) Control,
      treated with 22% carbamide peroxide (CP) followed by application of a toothpaste
      without active ingredient: (2) Nitrate, treated with 22% CP followed by
      application of a toothpaste containing 5% potassium nitrate and 2% sodium
      fluoride: (3) Strontium, treated with 22% CP followed by application of a
      toothpaste containing 10% strontium chloride. An air jet was used to evaluate
      post-bleaching sensitivity associated with a modified visual analogue scale
      (VAS). A spectrophotometer was used to measure the color of the maxillary
      incisors. RESULTS: The Friedman vs Kruskal-Wallis tests showed that the tooth
      sensitivity associated with the experimental groups during 10 days of bleaching
      treatment was lower than that reported with the Control (P= 0.043). ANOVA showed
      that variation in DeltaE revealed no significant difference in tooth color among
      the groups for the different evaluation times (P= 0.923). CLINICAL SIGNIFICANCE:
      The use of a toothpaste containing 5% potassium nitrate associated with 22%
      carbamide peroxide improves symptoms of dentin sensitivity after 10 days of
      bleaching treatment.

PMID- 29178731
TI  - Clinical effect of a manual toothbrush with tapered filaments on dental plaque
      and gingivitis reduction.
AB  - PURPOSE: To evaluate the anti-plaque efficacy (Study 1) and the anti-gingivitis
      efficacy (Study 2) of a manual toothbrush with tapered bristles compared to
      marketed control manual toothbrushes. METHODS: Studies 1 and 2 were independent,
      randomized and controlled, single-center, examiner-blind clinical trials in
      generally healthy adults. Study 1 included a 2-day acclimation period, followed
      by a 5-day twice daily toothbrushing test phase with the assigned brush. Baseline
      and Day 5 pre- and post-brushing plaque levels were assessed via Turesky Modified
      Quigley-Hein Plaque Index (TMQHPI). In Study 2, subjects with existing gingivitis
      brushed with their assigned toothbrush twice daily for 4 weeks. Gingivitis was
      measured using the Mazza Modification of the Papillary Bleeding Index at Baseline
      and Weeks 2 and 4. In both trials, subjects were randomly assigned to either the
      manual toothbrush with tapered bristles (Oral-B Super Thin Indicator toothbrush,
      OM159) or the marketed control (Study 1: Oral-B Complete Clean & Sensitive
      toothbrush; Study 2: Crest Pro-Health Complete 7 Brush 35 toothbrush) for use
      with a regular fluoridated dentifrice. RESULTS: 40 (Study 1) and 63 (Study 2)
      subjects were randomized in each trial. In Study 1, both the tapered bristle and
      marketed control brushes provided significant (P< 0.0001) mean whole mouth plaque
      reductions at Day 1 and Day 5 post-brushing relative to pre-brushing as measured
      via TMQPHI, with no between-brush significant differences. Both groups showed a
      significant reduction in Day 5 post-brushing mean plaque scores versus Day 1 pre-
      brushing mean plaque scores (P< 0.0001), but the reductions were not
      significantly different between groups (P= 0.4274). In Study 2, both the tapered
      bristle brush and the marketed control brush produced significant (P< 0.0001)
      reductions in both gingivitis and number of gingival bleeding sites at both Weeks
      2 and 4 versus baseline. At Week 4, the tapered filament toothbrush group showed
      8.6% less gingivitis (P= 0.0017) and 33.4% fewer bleeding sites (P= 0.0030)
      versus the control brush. All toothbrushes were well-tolerated. CLINICAL
      SIGNIFICANCE: Twice daily customary use of a manual toothbrush with tapered
      bristles provided clinically meaningful plaque and gingivitis reduction benefits.

PMID- 29178732
TI  - Comparison of enamel bond fatigue durability of universal adhesives and two-step
      self-etch adhesives in self-etch mode.
AB  - PURPOSE: To comparatively evaluate universal adhesives and two-step self-etch
      adhesives for enamel bond fatigue durability in self-etch mode. METHODS: Three
      universal adhesives (Clearfil Universal Bond; G-Premio Bond; Scotchbond Universal
      Adhesive) and three two-step self-etch adhesives (Clearfil SE Bond; Clearfil SE
      Bond 2; OptiBond XTR) were used. The initial shear bond strength and shear
      fatigue strength of the adhesive to enamel in self-etch mode were determined.
      RESULTS: The initial shear bond strengths of the universal adhesives to enamel in
      self-etch mode was significantly lower than those of two-step self-etch adhesives
      and initial shear bond strengths were not influenced by type of adhesive in each
      adhesive category. The shear fatigue strengths of universal adhesives to enamel
      in self-etch mode were significantly lower than that of Clearfil SE Bond and
      Clearfil SE Bond 2, but similar to that OptiBond XTR. Unlike two-step self-etch
      adhesives, the initial shear bond strength and shear fatigue strength of
      universal adhesives to enamel in self-etch mode was not influenced by the type of
      adhesive. CLINICAL SIGNIFICANCE: This laboratory study showed that the enamel
      bond fatigue durability of universal adhesives was lower than Clearfil SE Bond
      and Clearfil SE Bond 2, similar to Optibond XTR, and was not influenced by type
      of adhesive, unlike two-step self-etch adhesives.

PMID- 29178733
TI  - The role of adhesive materials and oral biofilm in the failure of adhesive resin
      restorations.
AB  - PURPOSE: To critically discuss adhesive materials and oral cariogenic biofilm in
      terms of their potential relevance to the failures of adhesive restorations in
      the oral environment. METHODS: The literature regarding adhesive restoration
      failures was reviewed with particular emphasis on the chemistry of adhesive
      resins, weakness in dentin bonding, water fluids, cariogenic oral biofilm and the
      relations that influence failures. Particular attention was paid to evidence
      derived from clinical studies. RESULTS: There was much evidence that
      polymerization shrinkage is one of the main drawbacks of composite formulations.
      Stress results in debonding and marginal leakage into gaps with deleterious
      effects in bond strength, mechanical properties and the whole stability of
      restorations. Changes in resins permit passage of fluids and salivary proteins
      with a biological breakdown of the restorations. Esterases enzymes in human
      saliva catalyze exposed ester groups in composite producing monomer by-products,
      which can favor biofilm accumulation and secondary caries. Adhesive systems may
      not produce a dense hybrid layer in dentin. Very often this is related to the
      high viscous solubility and low wettability in dentin of the hydrophobic BisGMA
      monomer. Thus, dentin hybrid layer may suffer from hydrolysis using both the
      Etch&Rinse and Self-Etching adhesive systems. In addition, exposed and non-resin
      enveloped collagen fibers may be degraded by activation of the host-derived
      matrix metalloproteinase. Plaque accumulation is significantly influenced by the
      surface properties of the restorations. Biofilm at the contraction gap has
      demonstrated increased growth of Streptococcus mutans motivated by the chemical
      hydrolysis of the adhesive monomers at the margins. Streptococcus mutans is able
      to utilize some polysaccharides from the biofilm to increase the amount of acid
      in dental plaque with an increase in virulence and destruction of restorations.
      Stability of resin restorations in the oral environment is highly dependent on
      the structure of the monomers used in composite and adhesive systems. Still, the
      issues related to microleakage of fluids into the gap and bacteria leaching from
      the surface of composites represent the main causes of failure of adhesive
      restorations. CLINICAL SIGNIFICANCE: Modifications of adhesive materials are
      necessary to address their instability in the oral environment.

PMID- 29178734
TI  - NaF rinse and dentifrice concentrations on enamel lesion demineralization.
AB  - PURPOSE: To compare the in vitro effectiveness of two mouthrinses containing
      different concentrations of NaF to reduce enamel lesion demineralization.
      METHODS: Nine extracted caries-free molars were selected and cleaned. The teeth
      were painted with acid resistant varnish, leaving a 1 mm * 4 mm window exposed.
      The teeth were cycled in a demineralizing solution at pH 4.5 for a total for 96
      hours. The teeth were sectioned longitudinally through the unpainted window using
      a hard-tissue microtome, producing 96 sections. The sections were measured and
      photographed under polarized light microscopy using water and Thoulet's 1.47 as
      imbibing mediums. Six treatment groups were randomly created: (A) water control
      group, (B) 0.05% rinse group once a day (C) 0.02% rinse group twice a day, (D)
      1,500 ppm paste group used twice a day, (E) combination group containing 0.05%
      rinse once a day, and 1,500 ppm paste twice a day, and (F) combination group
      containing 0.02% rinse and 1,500 ppm paste twice a day. A 10-day cycling protocol
      was carried out. All sections were then re-measured and re-photographed. A
      statistical analysis was performed to detect any differences between pre- and
      post-treatment groups. RESULTS: There was a statistically significant difference
      in lesion depth between the water control group and the 1,500 ppm paste group as
      well as the 0.05% rinse in combination with 1,500 ppm paste group (P= 0.0184). No
      statistically significant differences were found between the control group and
      any other groups. A statistically significant difference was found in lesion area
      between the two rinse groups alone and the 1,500 ppm paste group, as well as the
      0.05% rinse in combination with the 1,500 ppm paste group (P= 0.0002). An
      analysis of the results suggested that both rinse concentrations performed
      equally well in reducing lesion demineralization when used alone. However, only
      the 0.05% rinse used in combination with 1,500 ppm paste decreased lesion
      demineralization as compared to the water control group, and was equally as
      effective as the 1,500 ppm paste alone. CLINICAL SIGNIFICANCE: Within the
      limitations of this in vitro study, it was found that a fluoride containing
      dentifrice (1,500 ppm) and a combination of a fluoride containing dentifrice
      (1,500 ppm) and a 0.05% (210 ppm) fluoride rinse were more effective at reducing
      demineralization of enamel lesions than sodium fluoride rinses at concentrations
      of 0.02% and 0.05% alone or the combination of 0.02% NaF rinse with fluoride
      toothpaste.

PMID- 29178735
TI  - Silver diamine fluoride, potassium iodide, and esthetic perception: An in vitro
      pilot study.
AB  - PURPOSE: To assess if there was a perceptible difference in staining of
      restorations in silver diamine fluoride (SDF)-treated teeth, with or without the
      subsequent application of potassium iodide (KI). METHODS: 20 extracted teeth with
      frank cavitated carious lesions were prepared with a spoon excavator to remove
      superficial soft carious dentin and then randomly divided into two groups of 10.
      The control group was treated with 38% SDF and then restored with glass-ionomer.
      The experimental group received similar treatment, with the additional step of KI
      applied before restoration. All teeth were subjected to 500 thermocycles between
      5 degrees C and 55 degrees C, followed by storage in artificial saliva at 37
      degrees C for 30 days. Three blinded examiners evaluated all 20 teeth for
      intensity of staining on a scale from 0-5. Wilcoxon rank sum test compared
      average staining intensity between control and experimental groups of teeth as
      perceived by each examiner. RESULTS: No significant differences were found (P
      values: 0.93, 0.67, and 0.97). An aggregate comparison of staining perception
      between control and experimental groups by repeated measure analysis was done
      treating the outcome as Poisson distribution also finding no significant
      difference (P= 0.82). CLINICAL SIGNIFICANCE: The application of potassium iodide
      after silver diamine fluoride on caries-affected teeth may improve initial
      esthetic appearance, but after placement of a glass ionomer restoration,
      potassium iodide does not seem to result in any significant difference in
      staining.

PMID- 29178736
TI  - Comparison of dental bleaching effects of ozone and hydrogen peroxide: An ex vivo
      study.
AB  - PURPOSE: To compare the efficacy of using ozone versus hydrogen peroxide (H2O2)
      for tooth bleaching. METHODS: 90 extracted teeth were allocated into two groups.
      Teeth in Group 1 (n= 45) were exposed to ozone for 60 seconds; ozone was produced
      by healOzone x4 machine (healOzone x4), and was applied to teeth through special
      disposable silicone cups. The silicone cups allowed total seal and avoided gas
      escape as the machine is devised to work only if the cup guarantees perfect seal
      and thus secure the safety of the machine for human use. Teeth in Group 2 (n= 45)
      were treated with 38% H2O2 for 20 minutes. The shade of teeth was recorded for
      both groups at base line, after application of ozone in Group 1, and after
      application of H2O2 in Group 2. The reading for L* a* b* values and Vita Classic
      shades were recorded using the Colorimeter Konica-Minolta CR-400. The
      statistically significant differences were set at P<= 0.05. RESULTS: The teeth in
      both groups acquired lighter shades after bleaching (P< 0.001). In addition,
      baseline L* shade values were increased and b* shade values were decreased (means
      lighter shades) after bleaching in both groups (P< 0.01). However, baseline a*
      shade values were not significantly changed after bleaching with ozone in Group 1
      (P= 0.682). In contrast, a* shade values were significantly decreased after
      bleaching with H2O2 in Group 2 (P= 0.005). Furthermore, final shades achieved
      after bleaching were not significantly different between groups (P> 0.05). In
      conclusion, application of ozone for 60 seconds or application of 38% of H2O2 for
      20 minutes resulted in teeth with lighter shades. Bleaching by application of
      ozone for 60 seconds would result in similar outcomes to bleaching with 38% H2O2.
      CLINICAL SIGNIFICANCE: This is the first study to compare bleaching effects of
      ozone and hydrogen peroxide on natural human teeth. It might be suitable to
      consider ozone for dental bleaching since comparing to H2O2 it could potentially
      reduce the time, side effects and cost of treatment. Also, application of ozone
      is better controlled and more convenient and measurable as it is delivered by a
      machine that can manage the concentration, volume, delivery site and timing of
      delivered ozone.

PMID- 29178737
TI  - Effect of resin cement, aging process, and root level on the bond strength of
      fiber-posts: An in vitro study.
AB  - PURPOSE: To compare the push-out bond strength (POBS) of two resin cement systems
      (total-etch versus self-etch) for cementing FRC (fiber-reinforced composite)
      posts in three different thermocycling aging periods (40,000; 20,000; and none)
      using thermocycling and three root levels (apical, middle, and coronal). METHODS:
      60 bicuspid single rooted natural teeth were endodontically treated and post
      spaces were prepared to receive a fiber-post (RelyX FiberPost) cemented with
      either total-etch (RelyX Ultimate) or self-etch (RelyX Unicem) cement. Teeth were
      randomly allocated into six groups (n= 10): G1: Control (Ultimate without
      thermocycling); G2: Ultimate (20,000 cycles); G3: Ultimate (40,000 cycles); G4:
      Unicem without thermocycling; G5: Unicem (20,000 cycles); and G6: Unicem (40,000
      cycles). POBS was determined by using a push-out test on a universal testing
      machine. Additionally, failure mode of each specimen was observed under a
      stereomicroscope at x40 magnification and scanning electron microscope (SEM)
      examination of selected samples. A nested general linear model was created for
      statistical significance P< 0.05. Post-hoc tests were carried out using pair-wise
      comparisons with a Bonferroni adjustment. RESULTS: No significant differences
      were found on the bond strengths between the resin cements (P= 0.856). Regarding
      aging effect, bond strengths of the 40,000 cycle groups (G3/G6) were
      significantly lower than 20,000 cycle groups (G2/G5). In addition, the POBS of
      the specimens collected from the coronal third of the roots were significantly
      lower than specimens from the apical third regardless of the type of cement used.
      Regarding types of failures, adhesive failure (post/cement) was significantly
      higher in total-etch groups (G1-G3) than the self-etch groups (G4-G6). Adhesive
      failure (dentin/cement) was significantly higher in self-etch groups than the
      total-etch groups. CLINICAL SIGNIFICANCE: Within the limitations of this study,
      the bond strength to root canal dentin of self-etch and total-etch cements
      demonstrated reliable results and was not affected by the type of resin cement.
      Simplification of technique is an evident advantage of these materials in
      clinical practice.

PMID- 29178739
TI  - The effects of overhang amalgam restoration on levels of cytokines, gingival
      crevicular fluid volume and some periodontal parameters.
AB  - PURPOSE: To evaluate clinical periodontal findings and GCF levels of tumor
      necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8)
      in patients with overhang amalgam restorations before and after overhang
      restoration removal. METHODS: 22 volunteer subjects (age range: 22-42 years old)
      with 22 overhang Class II amalgam restorations were selected. GCF samples were
      obtained from adjacent and contralateral teeth for IL-6, IL-8 and TNF-alpha
      measurements and analyzed using enzyme-linked immunosorbent assay (ELISA) kits.
      The amalgam overhangs were removed and the readings were repeated at the end of 1
      week. Clinical periodontal assessments, including gingival index (GI) and plaque
      index (PI) were performed at baseline and after 1 week. Data were analyzed using
      the paired t-test and independent sample t-test at a significance level of 0.05.
      Correlations were investigated using Pearson correlation analysis. RESULTS: A
      significant reduction in GI and PI was observed after removal of the overhanging
      restoration on Day 7. (P< 0.05) However, there was no significant difference
      between IL-6 (P= 0.857), IL-8 (P= 0.579) and TNF-alpha (P= 0.958) levels before
      and after overhang restoration removal. There were no significant correlations
      between laboratory findings and clinical parameters. CLINICAL SIGNIFICANCE:
      Dental restorations may produce periodontal disease and may alter tooth form,
      surface integrity, relationship with the periodontium and adjacent teeth. The
      marginal edge located in the gingival sulcus is likely the cause of the
      inflammatory reaction. This study showed significant improvement in clinical
      periodontal parameters after removing the overhangs of restorations.

PMID- 29178738
TI  - Salivary IL-6 and IL-10 levels in subjects with obesity and gingivitis.
AB  - PURPOSE: To evaluate the association between cytokines IL-6 and IL-10 in saliva,
      obesity and periodontal disease. METHODS: The study was carried out in 40
      subjects: 20 obese subjects with gingivitis and 20 non-obese subjects with
      gingivitis (controls). Periodontal parameters such as gingival index (GI) and
      plaque index (PI) of subjects were recorded. Saliva samples were used for
      measuring IL-6 and IL-10 levels by ELISA method. RESULTS: Saliva IL-6 levels were
      significantly higher in obese subjects than those of non-obese subjects (P=
      0.002). When total groups were evaluated, negative significant correlation
      between GI and salivary IL-10 levels (r= -0.452, P= 0.003) and positive
      correlations between salivary IL-6 level and body mass index (BMI) (r= 0.369, P=
      0.019) were found. There was a negative correlation between the GI and salivary
      IL-10 levels in obese subjects (r= -0.548, P= 0.012). Also there was a positive
      correlation between the salivary level of IL-6 and IL-10 in obese subjects (r=
      0.594, P= 0.006). CLINICAL SIGNIFICANCE: Obesity and adipose tissues can affect
      periodontal health by altering the levels of IL-6 and IL-10. IL-6 in saliva
      clearly increased in subjects with obesity compared to subjects without obesity.
      Also negative correlations between saliva IL-10 levels and GI were found in the
      total group and obese subjects.

PMID- 29178740
TI  - Dentin hypersensitivity reduction using an arginine-based approach after non
      surgical periodontal treatment.
AB  - PURPOSE: To determine the efficacy of two oral hygiene regimens in the reduction
      of dentin hypersensitivity (DH) on subjects undergoing non-surgical periodontal
      treatment (NST), over a period of 8 weeks. METHODS: 60 subjects that were
      randomly assigned to: Test group - NST followed in-office application of an
      arginine-based professional paste and toothbrushing with arginine-based
      toothpaste at home (n= 30) and Control group - NST followed in-office application
      of a fluoride-free prophylaxis paste and toothbrushing with a toothpaste based on
      sodium monofluorophosphate 0.76%, at home (n= 30). Air blast sensitivity
      assessments were made using the Schiff scale. The sensitivity parameters were
      measured at baseline, 1, 4 and 8 weeks. RESULTS: After 1 week, DH reduction was
      statistically significant for the test group (63.6%) compared to baseline, while
      no significant reduction was observed for the Control group (4.8%). After 4-8
      weeks, the reductions were 81.6%/86.3% for the test group and 9.5%/14.2% for the
      Control group. When comparing the two groups, the test group showed a superior DH
      reduction in all evaluation periods (P< 0.05). Within the limits of the present
      study, it was concluded that the test oral hygiene regimen can effectively reduce
      dentin hypersensitivity during the most critical period after non-surgical
      periodontal treatment (up to 8 weeks). CLINICAL SIGNIFICANCE: The arginine-based
      approach provided significantly greater dentin hypersensitivity (DH) relief after
      non-surgical periodontal treatment (NST) when compared to the control. The
      combination of the in-office paste application with the daily used toothpaste may
      be a useful tool to reduce DH, an unpleasant and common condition that affects a
      large number of subjects, particularly during the initial weeks following NST.

PMID- 29178741
TI  - Analysis of the biofilm formed on the surface of a glass-ionomer cement
      associated with different concentrations of chlorhexidine diacetate.
AB  - PURPOSE: This cross-over in situ experiment evaluated the microbial composition
      and quantified the total polysaccharides in the biofilm formed on the surface of
      a high viscosity glass-ionomer cement (GIC) mixed with chlorhexidine diacetate
      (CHX) in concentrations of 0.5%, 1% and 2%. GIC without CHX was used as control.
      METHODS: The volunteers (n= 8) tested each material for a 7-day period, by using
      a palatal acrylic device containing four round specimens, all fabricated with the
      same material. An increasing order of CHX concentration and a 15-day washout
      period between each concentration was adopted. The biofilm formed was collected
      and inoculated in specific culture media and thereafter, the total
      microorganisms, total streptococci, Streptococcus mutans and Lactobacillus spp
      were counted. Total polysaccharides were quantified by using a phenol-sulfuric
      method. Microbiologic data were analyzed by ANOVA for repeated measures and Tukey
      tests, and the total polysaccharide content by Friedman and Dunn's tests.
      Significance level was set at 5%. RESULTS: Microorganism counts showed
      statistically significant differences among groups only for Lactobacillus (P<
      0.05), that were significantly higher for group GIC+CHX 2% compared with GIC and
      GIC+CHX 0.5%. However, the concentration of total polysaccharides in the biofilm
      was lower for groups containing 1% and 2% of CHX. CLINICAL SIGNIFICANCE: The
      addition of chlorhexidine in the studied concentrations did not reduce the
      microorganism counts, but caused reduction of biofilm density.

PMID- 29178742
TI  - The influence of two different curing regimens on light energy transmission
      through bulk-fill resin composites and Vickers hardness.
AB  - PURPOSE: To compare the total light energy transmission (J/cm2) through bulk-fill
      composite materials (BFMs) and Vickers hardness (VH) using a single-peak light
      curing unit (LCU) using two curing regimens. METHODS: Samples (n= 5) of viscous
      BFMs, Tetric EvoCeram Bulk Fill (TBF), X-tra fil (XF), and flowable BFMs, SureFil
      SDR (SDR), and X-tra base (XB) were prepared in 4 mm deep rings. The control was
      Tetric EvoCeram (TEC), a conventional composite. Using MARC-RC, the irradiance
      delivered to the top surface of the samples was adjusted to either 800 mW/cm2 for
      20 seconds (16 J/cm2) or 1,600 mW/cm2 for 10 seconds (16 J/cm2). Samples were
      stored post-irradiation at 22 +/- 2 degrees C for 24 hours. Top and bottom
      surface VH were measured and Bottom/Top (B/T) VH ratios were calculated. Data
      were analyzed using one-way ANOVA (alpha= 0.05). RESULTS: Total energy
      transmission for all materials ranged from 1.0 J/cm2 (6.1%) to 2.7 J/cm2 (16.9%).
      There was a statistically significant difference for total energy transmission to
      the bottom surface, more being transmitted at 800 mW/cm2 x 20 (P< 0.001). XB and
      TEC were significantly different, with higher B/T VH ratio when cured at 800
      mW/cm2 x 20 seconds (P< 0.001). There was no statistically significant difference
      for TBF, XF and SDR (P> 0.05) with either curing regimen. CLINICAL SIGNIFICANCE:
      The degree of cure was material-dependent and increasing curing time may be more
      important than LCU tip irradiation values. Manufacturer's recommended total
      energy regimen may not always be adequate for effective curing. Some bulk-fill
      materials, containing additional photo-sensitivity to lower wave lengths, may be
      adequately cured using a single-peak LCU.

PMID- 29178743
TI  - Influence of de/remineralization of enamel on the tensile bond strength of etch
      and-rinse and self-etching adhesives.
AB  - PURPOSE: To evaluate the bonding behavior of resin composite and different
      adhesives applied to demineralized or remineralized enamel. METHODS: Bovine tooth
      crowns were polished to prepare a 5 mm2 enamel bonding area, and divided into
      five groups (n= 48) according to the surface treatment: CONT (sound enamel
      control), DEM (demineralized with acid to create white spot lesions), REMS (DEM
      remineralized with artificial saliva), REMF (DEM remineralized with sodium
      fluoride) and INF (DEM infiltrated with Icon resin infiltrant). The surface
      treated teeth were divided into two subgroups (n= 24) according to adhesive type:
      ER (etch-and-rinse; Single Bond Universal) and SE (self-etching; Clearfill S3
      Bond), and further subdivided into two categories (n= 12) according to aging
      process: Thermo (thermocycling) and NA (no aging). Composite blocks were made
      over bonded enamel and sectioned for microtensile bond strength (MTBS) testing.
      Data were analyzed with three-way ANOVA and post-hoc Tukey's test (alpha= 0.05).
      RESULTS: Significant differences were observed for enamel surface treatment (P<
      0.0001), adhesive type (P< 0.0001) and aging (P< 0.0001). CONT and INF groups had
      higher MTBS than the other groups; Single Bond Universal had higher MTBS than
      Clearfil S3 Bond; thermo-aging resulted in lower MTBS irrespective of adhesive
      type and surface treatment condition. The predominant failure mode was mixed for
      all groups. Enamel surface infiltrated with Icon does not interfere with adhesive
      resin bonding procedures. CLINICAL SIGNIFICANCE: Treatment of enamel surface
      containing white spot lesions or cavities with cavosurface margins in partially
      demineralized enamel can benefit from infiltration with a low viscosity resin
      infiltrant prior to adhesive bonding of resin composites.

PMID- 29178744
TI  - The influence of two different curing regimens on light energy transmission
      through bulk-fill resin composites and Vickers hardness.
AB  - PURPOSE: To evaluate the presence and length of microcracks in resin-based
      materials finished with different techniques, using optical coherence tomography
      (OCT). METHODS: Standardized Class V preparations (3x2x2mm) were made in the
      facial and lingual surfaces of 20 recently-extracted human third molars. 20
      preparations were restored with a resin-based composite material (RBC; Filtek
      Supreme Ultra) and the other 20 with a resin-modified glass-ionomer material
      (RMGI; Ketac Nano). After final polymerization, specimens were further stratified
      by finishing system: aluminum oxide discs (Sof-Lex) or spiral fluted carbide bur
      series (H48L). By random allocation, each extracted tooth therefore received one
      RBC and one RMGI restoration, and equal numbers of restorations from each
      material were finished using each finishing system (n= 10). After 24 hours of
      storage in 100% humidity at room temperature, the specimens were evaluated at x20
      to x600 under environmental SEM. Cross-sectional occlusal-cervical B-mode images
      were obtained in increments of 25 mm from the mesial margin to the distal margin
      of the restoration using a spectral-domain (SD) OCT system and analyzed using
      Image J software to identify and measure microcrack penetration into each
      restoration. The total length (mm) at the point of the deepest microcrack
      penetration in each specimen was recorded. Data were statistically analyzed using
      a t-test. RESULTS: No microcracks were observed in the RBC samples. However,
      microcrack presence was identified in all of the RMGI specimens. The t-test
      showed a statistically significant difference (P< 0.05) in mean microcrack length
      values based on the finishing technique used for the RMGI samples. [SofLex: 0.67
      (+/- 0.28) mm; carbide: 1.26 (+/- 0.30)] mm. Two-way ANOVA showed significant
      differences in the factors "finishing technique" and "restorative material" (P<
      0.001). The interaction of these two factors was also statistically significant
      (P< 0.001). For the tested RMGI, Tukey post-hoc test revealed that the finishing
      with aluminum oxide groups resulted in statistically significant lower mean
      microcrack length when compared to spiral fluted carbide burs (P< 0.001).
      CLINICAL SIGNIFICANCE: Resin-modified glass-ionomer (RMGI) is more susceptible to
      microcrack presence than resin-based composites. Also, aluminum oxide discs
      produced lower values of mean microcrack length than spiral fluted carbide burs
      after the finishing procedure of RMGI restorations.

PMID- 29178745
TI  - Clinical performance of bonded ceramic inlays/onlays: A 5- to 18-year
      retrospective longitudinal study.
AB  - PURPOSE: This retrospective longitudinal study evaluated the clinical performance
      of bonded ceramic inlays/onlays, placed by the first author in his private
      practice, in a 5 to 18-year period. METHODS: The patients evaluated had been
      treated in the office for at least 7 years and were still in the practice up to
      year 2013. 130 randomly selected patients agreed to participate in the study. 93
      bonded ceramic inlays/onlays (BCRs), were placed on posterior teeth in 47
      subjects. Gender, age, tooth preparation, number, type, extent, location, quality
      and survival of the restorations, ceramic materials, luting resins cements,
      parafunctional habits, secondary caries and maintenance therapy were the
      variables evaluated. Cohen 's Kappa coefficient, on the quality analysis of the
      restorations, ranged from 0.78 to 1. Fisher 's exact test, Chi Square test,
      Kruskal-Wallis test and Mann-Whitney non-parametric test were indicated to
      analyze significant differences. RESULTS: At the initial examination, 87 (93.5%)
      restorations were in function and six failed (6.5%). 81 (93%) were rated as
      clinical successes. The observed mean survival time of those that remained
      functional was 11 years. The standard deviation was 4 years, with a 95% CI for
      the overall observed mean survival time (10 years-11 years, 9 months). 87 of 93
      BCRs had a functional success of 93.5%, with an observed mean survival of 11
      years. The clinical performance of bonded ceramic onlays was very acceptable.
      CLINICAL SIGNIFICANCE: Bonded ceramic onlays showed a predictable, esthetic, and
      functional treatment, with acceptable longevity.

PMID- 29178746
TI  - A randomized 3-month clinical comparison of a power toothbrush to a manual
      toothbrush in the reduction of gingivitis.
AB  - PURPOSE: To compare the anti-gingivitis effect of a power toothbrush relative to
      a manual toothbrush control. METHODS: This was a 3-month, randomized and
      controlled, single-center, parallel group, examiner-blinded clinical study. 123
      Chinese adults in good general health and with at least 15 gingival bleeding
      sites, as measured by the Gingival Bleeding Index, were enrolled into the study.
      At baseline, pre-treatment gingivitis levels were assessed using the Mazza
      Bleeding Index. Subjects were then randomly assigned to receive either an
      oscillating-rotating power toothbrush [Oral-B Professional Care 7000 (D17u/EB17)]
      or a flat-trim manual toothbrush with tapered filaments (Lion Dentor Systema).
      Subjects brushed at home twice-daily with their assigned toothbrush and a
      marketed sodium fluoride dentifrice (Crest Cavity Protection dentifrice), and
      were reevaluated at Months 1, 2, and 3. RESULTS: 113 evaluable subjects completed
      the study. Both groups showed significant reductions in gingivitis from baseline
      for all time points measured (P< 0.001). At Months 1, 2 and 3, the power
      toothbrush demonstrated significantly greater gingivitis reductions of 7.11%,
      9.20% and 8.47%, respectively, than the manual toothbrush (P< 0.01), and
      significantly fewer bleeding sites (17.3%, 23.9% and 24.3%, respectively, P<
      0.05). No adverse events were reported or observed for either brush during the
      study. CLINICAL SIGNIFICANCE: The power brush provided statistically
      significantly greater reductions in gingivitis compared with a manual toothbrush
      at Months 1, 2 and 3.

PMID- 29178747
TI  - Correlation among periodontal health status, maternal age and pre-term low birth
      weight.
AB  - PURPOSE: To assess correlations between periodontal status, maternal age and
      adverse pregnancy outcomes, such as pre-term and low birth weight in a sample of
      pregnant women. METHODS: Study population was represented by outpatient pregnant
      women, gestational age > 26 weeks. Medical history questionnaires were
      administered to all participants who underwent clinical evaluation; clinical
      obstetric outcome records were collected after delivery. A questionnaire was
      administered regarding personal information, socio-economic status, oral hygiene
      habits, and oral health conditions. A clinical oral examination was performed to
      collect Simplified Oral Hygiene Index (OHI-S) and Community Periodontal Index
      (CPI). Pregnancy outcome records included: delivery week, kind and causes of
      delivery, any relevant complications, and birth weight. Descriptive statistics
      were used to depict the data from the questionnaire while the relationship
      between delivery week, birth weight, maternal age and periodontal status was
      evaluated through multivariate tests of significance. RESULTS: 88 pregnant women
      were enrolled in the study. The results showed a statistically significant
      correlation (P< 0.001) among participants older than 40 years of age, between
      periodontal disease and adverse pregnancy outcomes. No statistical correlation
      was found among pre-term and low birth weight, smoking, ethnicity and educational
      level of mothers. The results highlight the importance of including a routine
      oral and periodontal health examination in pregnant women older than 40 years of
      age. CLINICAL SIGNIFICANCE: The correlation between periodontal status and
      adverse pregnancy outcomes in older mothers indicates the need for routine oral
      health examination and periodontal status assessment and care in pregnant women
      older than 40 years of age.

PMID- 29178748
TI  - Direct pulp capping versus root canal treatment in young permanent vital teeth
      with pulp exposure due to caries. A systematic review.
AB  - PURPOSE: To evaluate the available evidence on pulp capping procedures and root
      canal treatment in young permanent teeth with vital pulps exposed by caries.
      METHODS: The study was conducted as a systematic review of the literature. Three
      databases, PubMed, Web of Knowledge, and The Cochrane Library were searched.
      Reference lists of relevant articles were hand searched. The quality of all
      relevant publications was rated. RESULTS: Ten original scientific studies were
      included in the review. The quality was rated as low in all studies. The search
      failed to disclose any article directly comparing pulp capping and root canal
      treatment. The level of evidence was insufficient to draw any conclusions
      regarding the effectiveness of the two treatment concepts. High success rates are
      reported for pulp capping procedures in exposure due to caries, though it is not
      possible to compare them to success rates of root canal treatment. The review
      confirms the lack of high quality studies on the treatment of young permanent
      teeth with cariously exposed pulps. CLINICAL SIGNIFICANCE: For the treatment of
      young permanent teeth with pulp exposure due to caries there is currently no
      evidence to support the assumption on pulp capping being more beneficial than
      root canal treatment in achieving a symptom free tooth with normal periapical
      conditions.

PMID- 29178749
TI  - Effects of carbodiimide dentin surface treatment on resin-dentin bonding.
AB  - PURPOSE: To assess the effects of ethanol-based 1-ethyl-3-(3-dimethyl
      aminopropyl) carbodiimide (EDC) dentin surface treatment on resin-dentin bonding
      and dentin collagen fibril biodegradation. METHODS: Acid-etched dentin surfaces
      were pretreated with different concentrations of ethanol-based EDC solutions
      (0.01-2M) for 60 seconds, followed by two-step etch-and-rinse dentin adhesive
      application and resin composite bonding. Dentin surfaces pretreated with either
      ethanol alone or no pretreatment were used as controls. The specimens were
      subjected to microtensile bond strength testing after storage in 0.9% NaCl
      solution at 37 degrees C for either 24 hours or 90 days. Furthermore,
      demineralized dentin slabs with and without ethanol-based EDC pretreatment were
      exposed to a collagenase solution for 24 hours, and subsequent hydroxyproline
      release was measured using ELISA. Data were analyzed with ANOVA and multiple
      comparison tests at alpha= 0.05. RESULTS: The bond strength values were
      significantly lower for dentin surfaces pretreated with 1 and 2 M ethanol-based
      EDC than for the control surfaces (P< 0.05). The 0.01, 0.1, and 0.3 M ethanol
      based EDC pretreated groups obtained significantly higher bond strength values at
      90 days compared to controls. Hydroxyproline release measurements revealed that
      there were significantly lower levels released in the 0.3 and 1 M ethanol-based
      EDC pretreated specimens than for controls (P< 0.05). CLINICAL SIGNIFICANCE:
      Pretreatment of dentin surfaces with ethanol-based EDC solution <= 0.3M before
      resin composite bonding can improve the stability of the resin-dentin bond and
      prevent dentin collagen fibril biodegradation.

PMID- 29178750
TI  - Efficacy of a new filler-containing root coating material for dentin
      remineralization.
AB  - PURPOSE: To evaluate a new root coating material containing surface pre-reacted
      glass-ionomer (S-PRG) filler for remineralization of demineralized dentin.
      METHODS: The dentin was exposed on root surfaces of human third molars and
      demineralized by immersion in demineralization solution for 4 days. The
      demineralized dentin surface was divided into three areas. The center area was
      left untreated. The area on one side of the center area was coated with
      protective wax. The area on the other side was coated with one of four test
      materials: fluoride-containing S-PRG filler (PRG Barrier Coat: PR), fluoride
      containing bonding agent (Bond Force: BF), fluoride-containing glass-ionomer
      cement as a positive control (Fuji IX EXTRA: EX), or non-fluoride-containing
      bonding agent as a negative control (Clearfil MegaBond: MB). The samples were
      stored in remineralization solution for 7 days, and then cut into two slices. The
      mineral changes, defined as variation in mineral loss between wax-coated area and
      the central untreated area, were measured in one slice by transversal
      microradiography. The fluoride concentration was measured in the other slice by u
      particle-induced gamma/X-ray emission. Seven thin specimens (0.25-mm thickness)
      of each test material were used to determine fluoride ion release from the
      materials over 21 days. RESULTS: The mineral changes were greatest for EX,
      followed by PR, with no difference between BF and MB (P> 0.05). Regarding the
      fluoride concentrations in dentin, there was no difference between EX and PR (P>
      0.05). MB had the lowest value (P< 0.01). Fluoride release from EX was largest,
      followed by PR, with BF showing low fluoride release (P< 0.05). MB had no
      fluoride release. CLINICAL SIGNIFICANCE: A new coating material with S-PRG filler
      can be applied in a thin layer on root dentin, which could be especially useful
      for hard-to-access lesions. This material remineralized demineralized root dentin
      and had fluoride diffusion characteristics similar to those of glass-ionomer
      cement in vitro.

PMID- 29178751
TI  - Cytogenetic damage in exfoliated oral buccal cells by dental composites.
AB  - PURPOSE: To evaluate the possible geno/cytotoxic effects of dental composite
      materials by assessing the frequency of micronuclei formation and other nuclear
      abnormalities in the exfoliated buccal epithelium. METHODS: Swabs were taken from
      the buccal mucosa of 85 young healthy subjects. All participants had healthy
      dentition or dentition restored only with composite materials. Genotoxicity and
      cytotoxicity was assessed by micronucleus assay. RESULTS: The results indicated
      no significant difference in number of oral mucosa cells with micronuclei in
      subjects with different numbers of composite restored tooth surfaces (P= 0.476).
      Also, the number of restored surfaces had no effect on nuclear alterations
      closely related to cytotoxicity, such as karyolysis (P= 0.572), karyorrehexis (P=
      0.573) and picnosis (P= 0.765). CLINICAL SIGNIFICANCE: Despite doubts about the
      safe clinical use of resin composites, this study found no evidence that
      composite materials trigger long-term cytogenetic damage in the epithelial cells
      of buccal mucosa in humans. There is no objective and quantifiable evidence of
      genotoxicity induced by composite restorative materials in clinical practice.

PMID- 29178752
TI  - Fiber optics reflectance spectroscopy (45 degrees x: 45 degrees ) for color
      analysis of dental composite.
AB  - PURPOSE: To evaluate the application of a fiber optic reflectance spectroscopy
      (FORS) prototype probe for 45 degrees x: 45 degrees  FORS for determining color
      of dental materials. A portable spectrophotometer with a highly manageable fiber
      optics co-axial probe was used to apply 45 degrees x: 45 degrees  FORS for color
      matching in restorative dentistry. METHODS: The color coordinates in CIELAB space
      of two dental shade guides and of the corresponding photopolymerized composites
      were collected and compared. The 45 degrees x: 45 degrees  FORS with the co-axial
      probe (test system), the integrating sphere spectroscopy (reference system) and a
      commercial dental colorimeter (comparator system) were used to collect data and
      calculate color differences (DeltaE and DeltaE00). RESULTS: FORS system displayed
      high repeatability, reproducibility and accuracy. DeltaE and DeltaE00 values
      between the shade-guide, each other, and the corresponding composites resulted
      above the clinically acceptable limit. The 45 degrees x: 45 degrees  FORS test
      system demonstrated suitable in vitro performance for dental composite color
      evaluation. CLINICAL SIGNIFICANCE: 45 degrees x: 45 degrees  fiber optic
      reflectance spectroscopy allows reliable color analysis of small surfaces of
      dental composites, favoring the color matching of material with the closely
      surrounding dental tissue, and confirming significant color differences between
      shade guide tabs and photo-polymerized composites.

PMID- 29178753
TI  - Detection of occlusal caries with impedance spectroscopy and laser fluorescence
      before and after placement of fissure sealants: An in vitro study.
AB  - PURPOSE: To (1) investigate the influence of fissure sealants on impedance
      spectroscopy (ACIS) and laser fluorescence (LF) readings, (2) compare the
      performance of the ACIS device with the LF technique and visual inspection
      (ICDAS) in permanent molars with various degrees of occlusal caries, and (3)
      validate all methods against radiographs and histological hemi-sectioning.
      METHODS: 102 permanent molars were randomly selected to represent different
      stages of occlusal caries, from clinically sound to minor cavities. The teeth
      were examined by one trained examiner and scored with CarieScan PRO, the
      DIAGNOdent pen and ICDAS at baseline, after bleaching, etching and placement of a
      clear fissure sealant. A digital radiograph was exposed at baseline. After the
      assessments, the actual lesion depth was histologically determined. RESULTS:
      Bleaching did not affect the readings but significantly higher ACIS and LF-pen
      values were recorded after acid etching (P< 0.05). The placement of a fissure
      sealant increased the LF-pen readings significantly (P< 0.05) while no values
      could be obtained with the ACIS device. Both the baseline ACIS and LF-pen values
      were significantly associated (P< 0.05) with the lesion depth but visual
      inspection displayed the best correlation with radiographs and histology. The
      ACIS technology displayed high sensitivity and specificity for detecting
      extensive occlusal lesions. CLINICAL SIGNIFICANCE: The findings demonstrated that
      placement of a fissure sealant had a significant impact on the ACIS and LF-pen
      readings. Both methods mirrored the actual histological and radiographic lesion
      depth to various extents but could not match the performance of visual
      inspection.

PMID- 29178754
TI  - Heat generated during light-curing of restorative composites: Effect of curing
      light, exotherm, and experiment substrate.
AB  - PURPOSE: To investigate temperature rise, separating heat caused by irradiation
      and exotherm for three composites polymerized with three curing lights. The
      effect of substrate on temperature measurements was also determined. METHODS:
      Composite samples (n= 5) (Filtek Supreme Ultra, Filtek LS, and EsthetX HD) were
      placed on a thermocouple tip inside three substrates (aluminum, Delrin, and
      tooth). The composites were photoactivated using three curing lights (Elipar 2500
      QTH, SmartLite Max LED, DemiUltra LED) at 1 mm distance. Irradiance was 798, 980,
      and 1,135 mW/cm2, respectively. Exotherm was determined by subtracting post-cure
      from the polymerization temperature curves. ANOVA and Student-Newman-Keuls post
      hoc tests were used to analyze differences among peak temperatures and exotherms
      (significance level 0.05). RESULTS: SmartLite LED curing light resulted in higher
      peak temperatures and exotherms compared to the DemiUltra LED and QTH for all
      tested composites (16.9-20.4 degrees C vs 12.3-14.7 degrees C vs 8.9-9.7 degrees
      C). Thus, the LEDs produced higher temperature rises than the QTH, and the LED
      with lower irradiance caused higher temperature rise than the LED with higher
      irradiance. The silorane-based Filtek LS generated significantly higher exotherm
      than the methacrylate-based EsthetX HD and Filtek Supreme Ultra (6.2-7.6 degrees
      C vs 3.6-4.5 degrees C vs 2.7-3.6 degrees C). Substrate affected temperatures
      significantly. Temperature profiles found in Delrin substrate were comparable to
      tooth substrate, while aluminum substrate reduced temperatures 10-20 degrees.
      CLINICAL SIGNIFICANCE: Curing of restorative composites raises the temperature
      under a restoration due to irradiation and exothermic reaction; how much the
      temperature increases depends on curing light design, type of composite, and
      surrounding substrate. The silorane-based Filtek LS generated significantly
      higher exotherm than the methacrylate-based EsthetX HD and Filtek Supreme Ultra.

PMID- 29178755
TI  - Prognosis test by visualization of demineralized dentin under restorations to
      prevent initial wall-lesions initiated by lactic acid.
AB  - PURPOSE: To visualize the complete protection of restored dentin in the acidic
      environment by the complete impregnation of resin into demineralized dentin.
      METHODS: Class V cavities prepared in extracted human molars composed of enamel,
      cementum and dentin surfaces were sealed using either 4-META/MMA-TBB resin with
      conditioning periods of 10, 30, 60 seconds with 10% citric acid and 3% ferric
      chloride mixed aqueous solution (10-3) or Single-Bond 2 adhesives prior to
      restoration with light-cured resin-composite. Specimens were either immersed in
      artificial saliva or 0.1 mol/L buffered lactic acid solutions at 37 degrees C for
      14 days. After immersion in 0.5% basic fuchsin dye for 24 hours, the extent of
      dye penetration at the margin was measured. SEM micrography was used to
      investigate the quality of hybridized dentin when immersed in HCl followed by
      NaOCl solutions. RESULTS: After lactic acid exposure, dye penetration into the
      adjacent demineralized cementum/dentin was found to be significantly lower than
      the leakage distance under 30 and 60 seconds and Single-Bond 2 specimens. Leakage
      free margins were found in 10-second conditioning period specimens for both
      control and after soaking in buffered lactic solution with the stable hybridized
      dentin after chemical challenge. CLINICAL SIGNIFICANCE: A leakage-free
      interfacial layer, provided by complete hybrid layer formation, can block lactic
      acid penetration. Using this novel prognosis test for visualization of
      demineralized dentin, clinical restorations are likely to be more reliably
      predictable in the prevention of initial wall-lesions, post-operative
      hypersensitivity and/or pulpal infection.

PMID- 29178756
TI  - Porosity of flowable resin composites is not influenced by applicator tip
      diameter.
AB  - PURPOSE: To assess the influence of applicator tip diameter on the inclusion of
      porosities in three different flowable resin composites. METHODS: The initial
      porosity of three syringes [Filtek Supreme XTE Flowable (XTE), Grandio Flow
      (GRF), Gradia Direct Flo (GDF)] was determined by 3D tomography. 25 samples per
      syringe, i.e. 75 samples in total, were prepared using five applicator tips of
      different diameters (n= 5). The porosity of the 75 samples was assessed by 3D
      tomography. RESULTS: For each of the materials, the applicator tips, irrespective
      of type, all generated an increase in the average porosity percentage compared to
      the initial porosity of the syringes. For XTE and GRF, the applicator tips,
      irrespective of type, all generated a decrease in the average porosity volume
      compared to the initial average porosity volume in their respective syringes.
      Conversely, for GDF the average porosity volume of the samples was increased.
      Furthermore, for each of the materials, varying the diameter of the applicator
      tips had no significant influence on the porosity percentage and volume. Using
      the present study conditions, the applicator tip generated a variation in the
      initial porosity of the materials; however, the diameter of the tip had no
      influence on said variation. CLINICAL SIGNIFICANCE: It appears that practitioners
      can choose an applicator tip with a diameter that best suits the size and shape
      of the cavity to be filled using a syringe of flowable resin composite without
      this having any impact on the percentage and volume of porosities in the final
      filling of the cavity.

PMID- 29178757
TI  - Clinical and radiographic evaluation of white MTA versus formocresol pulpotomy: A
      48-month follow-up study.
AB  - PURPOSE: To determine whether there were differences between formocresol (FC) and
      white mineral trioxide aggregate (MTA) pulpotomy in terms of clinical and
      radiographic signs or effects upon the permanent successor over a long term.
      METHODS: A total of 212 molars (74 treated with FC and 138 with white MTA)
      corresponding to 129 subjects [66 females (51.1%) and 63 males (48.8%)] were
      evaluated. The coronal pulp was carefully amputated up to the entrance of the
      root canals using a sharp spoon excavator. Post-amputation bleeding was confirmed
      to be bright red and was seen to subside after applying 2-3 minutes of gentle
      pressure with a sterile cotton pellet. One group was treated with a 1:5 dilution
      of formocresol (20% Buckley's formocresol solution), while a second group was
      treated using white MTA powder (ProRoot). RESULTS: There were no significant
      differences in clinical success rate between the two groups (89.9% in the white
      MTA group versus 82.5% if the FC group). However, the radiographic success rate
      was significantly greater for white MTA versus FC. The radiographic failure rate
      in the molars treated with MTA was 7.9% versus 18.9% with FC. Regarding
      alterations in the timing of eruption, early and delayed eruption were
      respectively recorded in 7.24% and 8.69% of the cases in the MTA group, versus
      9.45% and 4.05% of the cases in the FC group. Thus, neither group showed relevant
      alterations in the timing of eruption. CLINICAL SIGNIFICANCE: Mineral trioxide
      aggregate showed a significantly greater radiographic success rate than
      formocresol in pulpotomy in primary teeth over 6 to 48 months of follow-up. MTA
      may be indicated as a substitute of formocresol in pulpotomy treatments of
      temporary molars, with no pathological consequences of any kind to the permanent
      successor premolar.

PMID- 29178758
TI  - Magnesium hydroxide-based dentifrice as an anti-erosive agent in an in situ
      intrinsic erosion model.
AB  - PURPOSE: To evaluate in situ a magnesium hydroxide-[Mg(OH)2] based dentifrice on
      enamel erosion. METHODS: Human dental enamel slabs were selected by surface
      microhardness and randomly assigned to one out of the following three groups
      (n=18): non-fluoride (control), NaF (1,450 ppm F), and Mg(OH)2 dentifrices. 18
      volunteers were enrolled in a randomized, crossover and double-blind study, with
      three phases in 5 days. They wore acrylic palatal appliances containing two human
      enamel slabs, which were treated with one of the three dentifrices. During each
      experimental phase, the specimens were subjected to erosion by immersion in 0.01
      M HCl for 60 seconds, 4x/day, followed by a 1-minute treatment with the
      correspondent slurry (saliva/dentifrice). Enamel changes were determined by the
      percentage of surface hardness loss (%SHL) and mechanical profilometry analysis.
      Data were analyzed by ANOVA, followed by Tukey's test (P< 0.05). RESULTS: The
      means (SD) for %SHL and surface wear (MUm) were, respectively, as follows:
      control [50.67(17.48), 2.70(1.24) ], NaF [45.45(15.44), 1.95(0.70) ] and Mg(OH)2
      [53.94(19.48), 1.95(0.67) ]. There was no statistically significant difference
      among the treated and control groups for %SHL (P= 0.349); however, for wear
      rates, a statistically significant difference was found between the groups
      treated with NaF and Mg(OH)2 and the control group (P= 0.04). CLINICAL
      SIGNIFICANCE: Dentifrices containing magnesium hydroxide or sodium fluoride might
      be an important strategy to minimize the effects of erosive challenges.

PMID- 29178759
TI  - The abrasive effect of commercial whitening toothpastes on eroded enamel.
AB  - PURPOSE: To evaluate the in vitro abrasive effect of commercial whitening
      toothpastes on eroded bovine enamel samples in respect to erosive tooth wear.
      METHODS: 72 bovine crowns were embedded, polished and subjected to the baseline
      profile analysis. The samples were then protected in 2/3 of the enamel surface
      and were randomly assigned to six groups (n= 12/group): G1: Oral-B 3D White, G2:
      Close-up Diamond Attraction Power White, G3: Sorriso Xtreme White 4D, G4: Colgate
      Luminous White, G5: Crest (conventional toothpaste), G6:erosion only (control).
      All samples were submitted to an erosive pH cycling (4 x 90 seconds in 0.1%
      citric acid, pH 2.5, per day) and abrasive challenges (2 x 15 seconds, per day)
      for 7 days. After the first and the last daily cycles, the samples were subjected
      to abrasive challenges, using a toothbrushing machine, soft toothbrushes and
      slurry of the tested toothpastes (1.5 N). Between the challenges, the samples
      were immersed in artificial saliva. The final profile was obtained and overlaid
      to the baseline profile for the calculation of the erosive tooth wear (MUm). The
      data were subjected to Kruskal-Wallis/Dunn tests (P< 0.05). RESULTS: G1 promoted
      the highest enamel wear (3.68+/-1.06 MUm), similarly to G3 (3.17+/- 0.80 MUm) and
      G4 (3.44+/- 1.29 MUm). G3 and G4 performed similarly between them and compared
      with G5 (2.35+/- 1.44 MUm). G2 (1.51+/- 0.95 MUm) and G6 (0.85+/- 0.36 MUm)
      showed the lowest enamel wear, which did not differ between them and from G5.
      Oral-B 3D White showed the highest abrasive potential while Close-up Diamond
      Attraction Power White showed the lowest abrasive potential on eroded enamel in
      vitro. CLINICAL SIGNIFICANCE: This study showed that some commercial whitening
      toothpastes, especially those containing pyrophosphate associated with hydrated
      silica, enhanced enamel erosive wear.

PMID- 29178760
TI  - Clinical evaluation of a toothpaste containing lysozyme for removal of extrinsic
      stains on the tooth surface: An 8-week, double-blind, randomized study.
AB  - PURPOSE: To assess the efficacy and safety of application of a toothpaste
      containing lysozyme to remove extrinsic stains on the tooth surface in an 8-week
      trial. METHODS: 70 adult participants with extrinsic staining of the tooth
      surface were recruited to this randomized, parallel-controlled, double-blind
      clinical trial. Participants were allocated randomly to the test group or the
      control group and the study procedure and correct usage of the toothpaste were
      explained to them. Staining, measured by the Lobene stain index, and any side
      effects, were recorded over the course of the 8 weeks. All data were analyzed
      using SAS software version 8.0. RESULTS: 69 participants completed the study. The
      value of the Lobene stain index was significantly reduced (P< 0.05) in the
      treatment group compared with the control group after both 4 and 8 weeks. No
      obvious side effects were observed. CLINICAL SIGNIFICANCE: The results of this
      clinical study showed that the toothpaste containing lysozyme was effective in
      removing extrinsic staining on the tooth surface.

PMID- 29178761
TI  - Long-term outcomes of pulpotomy in permanent teeth with irreversible pulpitis: A
      multi-center randomized controlled trial.
AB  - PURPOSE: To compare success rates of full pulpotomy (FP) with two endodontic
      biomaterials on symptomatic vital teeth with closed apices in the presence of
      apical periodontitis. METHODS: In this multicenter controlled clinical trial, 412
      volunteers met the inclusion criteria; they were all randomly allocated to either
      FP/ProRoot mineral trioxide aggregate (MTA) or FP/calcium enriched mixture (CEM)
      group. The subjects were followed up for 2 and 5 years to evaluate and compare
      the treatment outcomes. Data were analyzed using Chi square test and the multiple
      binary logistic regression model. RESULTS: Data for a total number of 344 and 304
      subjects were available for 2- and 5-year follow-ups. In terms of clinical
      outcomes, 2- and 5-year success rates of both groups were >= 98%, without
      significant differences. In terms of radiographic outcomes, the 2-year result of
      FP/MTA was significantly superior to FP/CEM (P= 0.005); however, the 5-year
      success rates were similar (P= 0.413). Age and preoperative periapical status did
      not affect the treatment outcomes. CLINICAL SIGNIFICANCE: Both MTA and CEM
      biomaterials were found to be equally effective pulpotomy agents for mature
      permanent molars with irreversible pulpitis and associated apical periodontitis
      in different age groups. The performance of this novel minimally invasive
      biotechnology may support a paradigm shift towards more biologic/conservative
      treatments in dentistry worldwide.

PMID- 29178762
TI  - Adverse effects of salivary contamination for adhesives in restorative dentistry.
      A literature review.
AB  - PURPOSE: To review and critically analyze the literature concerning the influence
      of salivary contamination on the bond quality of adhesives used in restorative
      materials by comparing and contrasting the different adhesive materials. METHODS:
      A detailed search on PUBMED, Cochrane Library, Google Scholar and Web of Science
      was carried out to identify publications on salivary contamination and dental
      adhesive materials, from 1990-2017 (March) which resulted in a total of 6,202 web
      identified publications. After screening titles/abstracts and de-duplicating, 54
      publications were selected that matched the requirements for this review. The
      condition for selection was English literature concerning the effect of salivary
      contamination on the adhesives used in restorative dentistry. The obtained
      articles were systematically evaluated. RESULTS: Salivary contamination of
      adhesives during restorative procedures statistically (64.6%) showed an adverse
      effect on adhesives, occurring either at one or many stages of restoration.
      Methodological dissimilarities impeded the direct comparison of the selected
      studies. Nevertheless, the 2-step etch and rinse adhesives were relatively less
      vulnerable to salivary contamination than the others. 65% of the evaluated
      studies for decontamination achieved improved bonding when the contaminated
      surface was subjected to some kind of decontamination procedure. However, the
      duration and other specificities were not standard in all the evaluations and
      need further research to assess the course of action. It is necessary to do long
      term studies to evaluate the effectiveness of contaminated adhesive over time.
      CLINICAL SIGNIFICANCE: Salivary contamination is a potential cause for poor bond
      quality of adhesive systems during restorative procedures and to provide a
      successful treatment, proper care must be taken to ensure the operating area is
      free from contamination. Understanding the properties of the materials and its
      constituents as well as considering measures to manage the potential
      vulnerabilities due to salivary contamination in the area of bonding might help a
      clinician to produce better results.

PMID- 29178763
TI  - Influence of different cavity preparation designs on fracture resistance of onlay
      and overlay restorations using different CAD/CAM materials.
AB  - PURPOSE: To evaluate fracture strength of different preparation designed onlay
      and overlay restorations produced by Computer Aided Design/Computer Aided
      Manufacturing (CAD/CAM) and three different new ceramic-polymer blocks. METHODS:
      Ninety-one extracted human mandibular molars were used in this study.
      Preparations were made as (1) Only functional cusps reduction, (2) Only
      functional cusps reduction+rounded shoulder finish line, (3) All cusps reduction,
      or (4) All cusps reduction+rounded shoulder finish line. Then these four cavity
      types were restored with three different materials: VITA Enamic, GC Cerasmart,
      Lava Ultimate. Thirteen groups were created by added control group (n= 7).
      Adhesive cementation was achieved by using a dual cured composite resin adhesive
      cement RelyX Ultimate. All samples were subjected to thermocycling for 5,000
      cycles in water baths between 50 degrees C and 55 degrees C. The fracture
      resistance of specimens was determined under compressive loads along the long
      axis of the restored teeth at 0.5 mm/minute crosshead speed until fracture with a
      universal test machine. Fracture types of restored groups were evaluated. For
      fracture resistance data, one-way ANOVA; for correlation between material type
      and preparation design, two-way ANOVA were used. Percentage table and Kruskal
      Wallis test were performed for analysis of fracture types. RESULTS: There was no
      significant difference between all the groups (one-way ANOVA, P> 0.05). Group 4
      showed statistically higher fracture strength values than Group 1 and no
      significant difference was found among other preparation designs by two-way ANOVA
      that compared all types of preparation designs regardless of material difference
      (P< 0.05). CLINICAL SIGNIFICANCE: The results of the present study could help
      clinicians regarding which materials and type of preparations should be selected
      for onlay and overlay restorations produced with newly introduced ceramic-polymer
      CAD/CAM materials.

PMID- 29178764
TI  - Initial microbial colonization of enamel in children with different levels of
      caries activity: An in situ study.
AB  - PURPOSE: To investigate patterns of overnight in situ microbial colonization of
      enamel in children. METHODS: Overall, 29 children (aged 5-9 years) participated
      in the study. Nine were caries-free with no decayed, missing, or filled teeth
      (DMFT), 11 were caries-rehabilitated (DMFT >= 2, no active carious lesions), and
      nine were caries-active (DMFT >= 2, at least two carious lesions). Bovine enamel
      samples were fixed on individual upper jaw splints stored overnight in situ. 4',6
      diamidino-2-phenylindole (DAPI) combined with Concanavalin A staining was applied
      for fluorescence microscopic visualization of total adherent bacteria and
      glucans. Fluorescence in situ hybridization (FISH) was used for distinction of
      eubacteria, streptococci, and Candida albicans. Salivary samples were
      investigated for Streptococcus mutans (S. mutans) by using CRT bacteria test and
      yeasts with Calcofluor white (CFW) staining. RESULTS: With all fluorescence
      methods, bacteria but not Candida albicans were detected on enamel samples. No
      statistically significant differences were observed in distribution patterns of
      the adherent bacteria between the groups. CFW staining indicated fungal
      structures in saliva samples of all participants. Based on CRT test results, the
      lowest amount of S. mutans were observed in caries-free children. Thus, initial
      microbial colonization patterns of enamel in children are not influenced by
      caries activity. CLINICAL SIGNIFICANCE: Caries activity in children may influence
      the process of initial bioadhesion and thus distribution patterns of bacterial
      attachment to the enamel surface. Investigation of in situ biofilm formation
      might provide valuable insights regarding the varying caries susceptibility in
      children.

PMID- 29178765
TI  - Ion release and in vitro enamel fluoride uptake associated with pit and fissure
      sealants containing microencapsulated remineralizing agents.
AB  - PURPOSE: To determine if pit-and-fissure sealants with microencapsulated
      remineralizing agents with sustained release of fluoride, calcium and phosphate
      ions could promote enamel fluoride uptake by demineralized tooth structure.
      METHODS: Sealants that contained 5 w/w% microcapsules with aqueous solutions of
      5M Ca(NO3)2 or 0.8M NaF or 6.0M K2HPO4 or a mixture of all three were prepared.
      Ion release profiles were measured as a function of time. Enamel fluoride uptake
      by demineralized tooth structure was determined. RESULTS: Sustained release of
      fluoride, calcium and phosphate ions from a sealant was demonstrated. Fluoride
      uptake by demineralized enamel was significantly increased compared to a control
      sealant manufactured without microcapsules (P< 0.01). Bovine enamel that
      contained 2.2+/-2.1 ug F/g of enamel prior to exposure to a sealant without
      microcapsules had 2.3+/-0.5 after 90 days. Enamel exposed to sealant with 5w/%
      NaF microcapsules went from 3.5+/-3.5 ug F/g of enamel prior to exposure to 148+/
      76 after 90 days. Enamel exposed to sealant with 2 w/w% NaF, 2 w/w% Ca(NO3)2 and
      1 w/w% K2HPO4 microcapsules went from 1.7+/-0.7 ug F/g of enamel prior to
      exposure to 190+/-137 after 90 days. CLINICAL SIGNIFICANCE: Sealants with
      encapsulated remineralizing agents were capable of releasing biologically
      available fluoride, calcium, and phosphate ions. Incorporation of these
      microcapsules in pit and fissure sealants is a promising method for
      remineralization determined by enamel fluoride uptake measurements.

PMID- 29178766
TI  - Light energy transmission and Vickers hardness ratio of bulk-fill resin based
      composites at different thicknesses cured by a dual-wave or a single-wave light
      curing unit.
AB  - PURPOSE: To quantify light energy transmission through two bulk-fill resin-based
      composites and to measure the top to bottom surface Vickers hardness ratio
      (VHratio) of samples of various incremental thicknesses, using either a single
      wave or dual-wave light curing unit (LCU). METHODS: Tetric EvoCeram Bulk Fill
      (TECBF) and SonicFill (SF) were studied. Using MARC-RC, the irradiance delivered
      to the top surface of the samples 2, 3, 4 and 5 mm thick (n= 5 for each
      thickness) was adjusted to 800 mW/cm2 for 20 seconds (16 J/cm2) using either a
      single-wave, Bluephase or a dual-wave, Bluephase G2 LCUs. Light energy
      transmission through to the bottom surface of the specimens was measured at real
      time using MARC-RC. The Vickers hardness (VH) was determined using Vickers micro
      hardness tester and the VHratio was calculated. Data were analyzed using a
      general linear model in Minitab 16; alpha= 0.05. RESULTS: TECBF was more
      translucent than SF (P< 0.05). The mean VHratio was higher than 80% in 2, 3 and 4
      mm increment thickness for both materials (except for 4 mm TECBF when cured with
      the dual-wave Bluephase G2). SF showed significantly higher VH ratio than TECBF
      at all different thickness levels (P< 0.05), except at the 2 mm level (P> 0.05).
      TECBF showed significantly greater VH ratio when cured with the single-wave
      Bluephase than when using the dual-wave Bluephase G2 (P< 0.05). CLINICAL
      SIGNIFICANCE: The transmission of light energy through to the bottom surface and
      the VHratio are material dependent. Although TECBF is more translucent than SF,
      it showed lower VHratio compared to SF when cured with dual-wave Bluephase G2.

PMID- 29178767
TI  - Effect of oxygen inhibition in universal adhesives on dentin bond durability and
      interfacial characteristics.
AB  - PURPOSE: To evaluate the effects of oxygen inhibition of universal adhesive on
      dentin bond durability and interfacial characteristics. METHODS: The three
      universal adhesives used were Scotchbond Universal Adhesive, Prime & Bond Elect,
      and G-Premio Bond. Shear bond strength (SBS) and shear fatigue strength (SFS) of
      resin composite bonded to adhesive with and without an oxygen inhibited layer
      (OIL) on dentin using total-etch and self-etch modes were determined. Surface
      free energy (SFE) and SFE parameters of cured adhesive with and without an OIL on
      dentin using total-etch and self-etch modes were also measured by the sessile
      drop method. RESULTS: The presence of an OIL in universal adhesives promoted
      higher SBS and SFS regardless of etching mode. In addition, regardless of
      adhesive type and etching modes, the specimens with an OIL showed a higher ratio
      of SFS/SBS than those without an OIL. Further, the SFEs, especially total SFE,
      polarity force and hydrogen bonding force, of cured adhesives with an OIL were
      significantly higher than those without an OIL. CLINICAL SIGNIFICANCE: The
      present findings indicated that the oxygen inhibition of universal adhesive did
      not impair the dentin bond durability and interfacial characteristics of the
      adhesive.

PMID- 29178768
TI  - A global approach to assess the economic benefits of increased consumption of
      sugar-free chewing gum.
AB  - PURPOSE: To analyze the influence of increasing the average consumption of sugar
      free gum (SFG) in 25 industrialized countries on dental expenditures due to
      caries by the national health care systems. It was assumed that large cost
      savings were possible, because the regular consumption of SFG significantly
      reduces the relative risk of caries and therefore, improves dental health, which
      reduces expenditures on dental treatments. METHODS: A budget impact analysis
      (BIA) was performed to model the decrease in the relative risk of caries and the
      subsequent cost savings for dental care. Annual consumption of SFG, dental
      expenditures due to caries, chewing frequencies by age groups and the relative
      risk reduction for caries due to the consumption of SFG were identified and used
      as model parameters. Three different scenarios for the increase in the number of
      SFG were calculated. Besides overall results for all countries together, analyses
      were conducted for countries grouped by regions and the Human Development Index
      (HDI). RESULTS: For the entity of all 25 analyzed countries together, possible
      annual cost savings range from US$805.77 M in the scenario with the lowest
      increase of SFG consumption up to US$18,248 billion in the scenario with the
      biggest increase of SFG consumption. Europe and the USA show potential cost
      savings of US$1,061 billion and US$2,071 billion per year, respectively, if all
      chewers increase their consumption of SFG by 1 piece per day. The analysis showed
      the potential cost savings in dental expenditures due to caries that can be
      achieved by only slightly increasing the consumption of SFG. The regular
      consumption of SFG cannot replace good dental hygiene like tooth brushing, but
      can have a significant impact on dental health, which can lead to increased cost
      savings for health care systems worldwide. CLINICAL SIGNIFICANCE: Based on the
      fact that a regular consumption of sugar-free chewing gum has the beneficial
      effect of reducing caries prevalence, an increased consumption may not only lead
      to improved dental health but significant cost savings in expenditures for dental
      treatment worldwide.

PMID- 29178769
TI  - Effects of desensitizing agents for cervical dentin hypersensitivity: A
      randomized clinical trial.
AB  - PURPOSE: To evaluate the clinical efficacy of five commercially available
      desensitizing agents with different mechanisms applied to hypersensitive teeth.
      METHODS: A randomized clinical trial was conducted on subjects suffering dentin
      hypersensitivity in Korea University Guro Hospital from October 2013 to April
      2015. A total of 64 subjects met the selection criteria and were randomly
      assigned to five commercially available desensitizing agents, and applied
      according to the manufacturers' instructions. Before and after application of
      desensitizing agents, subjects were evaluated with the Visual Analogue Scale
      (VAS) at baseline, 1 week, 1 month and 3 months. The difference between the
      degree of reduction of hypersensitivity in relation to time were evaluated with
      the repeated-measures ANOVA (P<0.05). RESULTS: Practitioner and subject-measured
      VAS values at 1 week, 1 month and 3 months showed a significant difference in all
      products compared with the first visit. On the other hand, no statistically
      significant differences between the products was shown. Desensitizing agents used
      in this clinical trial relieved dentin hypersensitivity up to 3 months. CLINICAL
      SIGNIFICANCE: The five tested desensitizing agents with different mechanisms were
      clinically effective in relieving dentin hypersensitivity up to 3 months and
      showed statistically significant pain reduction when compared to baseline scores.

PMID- 29178770
TI  - Antibiotic prophylaxis for preventing dental implant failure and postoperative
      infection: A systematic review of randomized controlled trials.
AB  - PURPOSE: To investigate whether prophylactic antibiotics are beneficial on
      patients undergoing routine dental implant placement procedures and to
      investigate which administration regimen is the most effective. METHODS: The
      primary outcome was implant failure; the secondary outcome was postoperative
      infection. In the fixed-effects model, the Mantel-Haenszel method was used to
      calculate pooled relative risks (RRs) at 95% confidence intervals (CIs). To
      determine the outcomes, the quality of available evidence was assessed using the
      Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
      RESULTS: Prophylactic antibiotics significantly decreased the incidence of
      implant failure (RR, 0.29; 95% CI, 0.15-0.55; P= 0.0002; I2= 0%) but did not
      decrease infection. There was no statistically significant difference between
      single preoperative antibiotics (SPA) and preoperative and postoperative
      antibiotics (PPA) while treating patients with dental implant failure (RR, 1.07;
      95% CI, 0.31-3.62; P= 0.92). No statistically significant difference was observed
      between SPA and PPA when prescribed to treat infection postoperatively (RR, 1.05;
      95% CI, 0.29-3.85; P= 0.94; I2= 0%). CLINICAL SIGNIFICANCE: The administration of
      prophylactic antibiotics significantly reduced the failure of dental implants
      under ordinary conditions. Furthermore, single preoperative antibiotics and
      preoperative and postoperative antibiotics had similar effects on dental implant
      failures and infections.

PMID- 29178771
TI  - Effect of different concentrations and application times of proanthocyanidin gels
      on dentin erosion.
AB  - PURPOSE: To analyze the effect of different concentrations and application times
      of proanthocyanidin gels on dentin before an erosive challenge in order to
      evaluate if there is a dose-response or application time-response relationship in
      the use of these gels for erosion prevention. METHODS: 80 bovine root dentin
      blocks were randomly and equally divided into 10 groups and treated according to
      the two factors under study (purified grape seed proanthocyanidin gel
      concentration and time of application): 0.05P1: 0.05% proanthocyanidin gel during
      1 minute; 0.05P5: 0.05% proanthocyanidin gel during 5 minutes; 1P1: 1%
      proanthocyanidin gel during 1 minute; 1P5: 1% proanthocyanidin gel during 5
      minutes; 5P1: 5% proanthocyanidin gel during 1 minute; 5P5: 5% proantho-cyanidin
      gel during 5 minutes; 10P1: 10% proanthocyanidin gel during 1 minute; 10P5: 10%
      proanthocyanidin gel during 5 minutes; Control 1: placebo gel during 1 minute;
      and Control 5: placebo gel during 5 minutes. The gels were applied over dentin
      blocks once before the first erosive challenge. After that, the blocks were
      subjected to three erosive cycles per day, during 5 days. Profilometry was used
      to quantify the dentin loss (um). Data were analyzed by two-way ANOVA and
      Fisher's test (P< 0.05). RESULTS: Statistical analysis showed that there was no
      significant difference between the application times. The different
      concentrations of proanthocianidin gels presented similar results (P> 0.05). All
      tested gels resulted in significantly less wear when compared to the placebo gel.
      CLINICAL SIGNIFICANCE: Grape seed proanthocyanidin gels could be considered as a
      promising therapy to diminish erosive dentin wear because it may interact with
      the exposed collagen, enhancing the demineralized organic matrix stabilization,
      which acts as a barrier against the diffusion of the acids from erosion.

PMID- 29178772
TI  - Antimicrobial action and long-term effect of overnight denture cleansers.
AB  - PURPOSE: To evaluate two denture cleansers for overnight soaking (0.5% sodium
      hypochlorite and peroxide alkaline) regarding efficacy against Candida spp.
      biofilms (randomized clinical trial) and their effects on the physical properties
      of a denture base acrylic resin simulating a period of 5 years of use (laboratory
      study). The Candida spp. were identified and their resistance to main antifungal
      agents was evaluated. METHODS: 32 complete denture wearers were instructed to
      brush their dentures three times a day and to soak them (>=8 hours) in: control -
      water (C); alkaline peroxide (AP); or 0.5% sodium hypochlorite (SH). According to
      a randomized sequence, each solution was used for three alternate periods of 7
      days. The antimicrobial action was performed by counting the colony forming units
      (CFU) of Candida spp. For collection of the biofilm, each upper complete denture
      was placed in a Petri dish, the internal surface was brushed (Tek brush) with
      saline solution for 2 minutes and the suspension was transferred to a test tube.
      After dilutions (10 0 to 10-3), aliquots of 50 uL were seeded inside Petri dishes
      containing Candida Chromagar. After incubation, the colonies were counted and the
      values of CFU/mL calculated. Data were transformed in log10 (CFU +1) and analyzed
      by the Friedman test (alpha= 0.05) followed by Wilcoxon and Bonferroni tests
      (alpha= 0.05). Each of the different species identified perfunctorily has been
      confirmed through the identification of yeasts kit. The resistance to antifungal
      agents (amphotericin B, nystatin, flucytosine, econazole, ketoconazole,
      miconazole and fluconazole) was also evaluated. Adverse effects were estimated on
      heat-polymerized resin specimens, simulating a 5-year period of overnight use.
      Acrylic resin specimens were randomly distributed into three groups: C: Control
      (distilled water); AP: alkaline peroxide; and SH: 0.5% sodium hypochlorite. Color
      change, surface roughness and flexural strength were evaluated at baseline and
      after immersion procedures. Data were compared by Kruskall-Wallis followed by
      Dunn's test (color change and surface roughness) and one-way ANOVA (flexural
      strength) (alpha= 0.05). RESULTS: There was a reduction of Candida spp. counts
      after using both solutions (AP and SH). The Candida spp. most often isolated was
      C. albicans, followed by the C. glabrata. Only 24.7% of isolate strains were
      resistant to at least one of the tested antifungals, highlighting azole
      compounds. Immersion in AP [ 5.73 (5.45-5.91)] caused significantly higher color
      change, with lower DeltaE values for C [1.12 (1.15-1.37) ] followed by SH [3.70
      (3.51-3.98) ]. The NBS values were classified as "slight" for C (1.12) group and
      " considerable" for AP (5.27) and SH (3.40). No solution altered surface
      roughness significantly. Flexural strength (in MPa) was significantly lower for C
      (64.59), AP (63.96 +/- 12.98) and SH (62.84 +/- 8.62) when compared to a group
      without any immersion (109.12 +/- 8.37). CLINICAL SIGNIFICANCE: Both solutions
      tested presented antimicrobial action against Candida spp. and may be useful for
      denture biofilm control, but should be used with caution as an overnight
      immersion solution since they may damage denture bases in the long-term. Candida
      was most frequently isolated at baseline and after using the products. Only 24.7%
      of isolate strains were resistant to at least one of the tested antifungals,
      especially with azole compounds.

PMID- 29178773
TI  - Comparison of nanofluoridated hydroxyapatite of varying fluoride content for
      dentin tubule occlusion.
AB  - PURPOSE: To evaluate the viability of a series of nano-fluoridated hydroxyapatite
      (nano-FHA) formulations of varying fluoride content for the occlusion of exposed
      dentin tubules, in comparison to nano-hydroxyapatite (nano-HA). METHODS: Nano-FHA
      powders with varying levels of fluoride ion were synthesized to substitute
      hydroxyl ions (-OH) present in hydroxyapatite (HA). Nano-FHA were defined as
      2nFHA,4nFHA,6nFHA, 8nFHA and 10nFHA, with the molar ratio of F(- to Ca243; of
      0.002,0.004,0.006,0.008 and 0.01, respectively. The powders were synthesized
      using a wet chemistry route, and characterized by transmission electron
      microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The
      methylthiazol tetrazolium (MTT) assay was used to assess cell viability toward
      nano-FHA. According to the content of F-, the nano-nFHA and nano-HA powders were
      divided into six groups, with the artificial saliva as control. They were spread
      over the dentin surface for 1 minute and repeated three times per day for 7
      consecutive days. After washing and brushing with distilled water for an
      additional 7 days, scanning electron microscopy was used to evaluate the in vitro
      plugging rate of the tubules and penetrating depth. RESULTS: The 2nFHA, 4nFHA,
      6nFHA, 8nFHA and 10nFHA powders were prepared and characterized. The 8nFHA had
      less crystallinity compared to 2nFHA,4nFHA, and 6nFHA.The MTT assay (from 12 to
      120 hours) showed that the cell viability of the L-929 fibroblasts in the 2nFHA,
      4nFHA, 6nFHA, 8nFHA, 10nFHA, and nano-HA groups ranged from 80.54+/- 3.35% to
      112.9+/- 4.8%. Most of the nano-FHA powders successfully occluded dentin tubules.
      The plugging rate of 8nFHA was significantly higher than that of the 2nFHA,
      4nFHA, 6nFHA and nano-HA groups. The penetrating depth of the 8nFHA group into
      the tubules was also significantly higher than that of the other nano-FHA and
      nano-HA group. CLINICAL SIGNIFICANCE: The nano-FHA formulation 8nFHA showed
      higher plugging rate and penetrating depth into the tubules. It has the potential
      to be used as a desensitizing agent in treating dentin hypersensitivity with
      better long-term durability and efficacy of dentin tubule occlusion.

PMID- 29178774
TI  - Binding of Polythiophenes to Amyloids: Structural Mapping of the Pharmacophore.
AB  - Luminescent conjugated polythiophenes bind to amyloid proteins with high
      affinity. Their fluorescence properties, which are modulated by the detailed
      conformation in the bound state, are highly sensitive to structural features of
      the amyloid. Polythiophenes therefore represent diagnostic markers for the
      detection and differentiation of pathological amyloid aggregates. We clarify the
      binding site and mode of two different polythiophenes to fibrils of the prion
      domain of the HET-s protein by solid-state NMR and correlate these findings with
      their fluorescence properties. We demonstrate how amyloid dyes recognize distinct
      binding sites with specific topological features. Regularly spaced surface charge
      patterns and well-accessible grooves on the fibril surface define the
      pharmacophore of the amyloid, which in turn determines the binding mode and
      fluorescence wavelength of the polythiophene.

PMID- 29178775
TI  - Brush-Like Cobalt Nitride Anchored Carbon Nanofiber Membrane: Current Collector
      Catalyst Integrated Cathode for Long Cycle Li-O2 Batteries.
AB  - To achieve a high reversibility and long cycle life for lithium-oxygen (Li-O2)
      batteries, the irreversible formation of Li2O2, inevitable side reactions, and
      poor charge transport at the cathode interfaces should be overcome. Here, we
      report a rational design of air cathode using a cobalt nitride (Co4N)
      functionalized carbon nanofiber (CNF) membrane as current collector-catalyst
      integrated air cathode. Brush-like Co4N nanorods are uniformly anchored on
      conductive electrospun CNF papers via hydrothermal growth of Co(OH)F nanorods
      followed by nitridation step. Co4N-decorated CNF (Co4N/CNF) cathode exhibited
      excellent electrochemical performance with outstanding stability for over 177
      cycles in Li-O2 cells. During cycling, metallic Co4N nanorods provide sufficient
      accessible reaction sites as well as facile electron transport pathway throughout
      the continuously networked CNF. Furthermore, thin oxide layer (<10 nm) formed on
      the surface of Co4N nanorods promote reversible formation/decomposition of film
      type Li2O2, leading to significant reduction in overpotential gap (~1.23 V at 700
      mAh g-1). Moreover, pouch-type Li-air cells using Co4N/CNF cathode stably
      operated in real air atmosphere even under 180 degrees  bending. The results
      demonstrate that the favorable formation/decomposition of reaction products and
      mediation of side reactions are hugely governed by the suitable surface chemistry
      and tailored structure of cathode materials, which are essential for real Li-air
      battery applications.

PMID- 29178776
TI  - Evidence for Chemical and Electronic Nonuniformities in the Formation of the
      Interface of RbF-Treated Cu(In,Ga)Se2 with CdS.
AB  - We report on the initial stages of CdS buffer layer formation on Cu(In,Ga)Se2
      (CIGSe) thin-film solar cell absorbers subjected to rubidium fluoride (RbF)
      postdeposition treatment (PDT). A detailed characterization of the CIGSe/CdS
      interface for different chemical bath deposition (CBD) times of the CdS layer is
      obtained from spatially resolved atomic and Kelvin probe force microscopy and
      laterally integrating X-ray spectroscopies. The observed spatial inhomogeneity in
      the interface's structural, chemical, and electronic properties of samples
      undergoing up to 3 min of CBD treatments is indicative of a complex interface
      formation including an incomplete coverage and/or nonuniform composition of the
      buffer layer. It is expected that this result impacts solar cell performance, in
      particular when reducing the CdS layer thickness (e.g., in an attempt to increase
      the collection in the ultraviolet wavelength region). Our work provides important
      findings on the absorber/buffer interface formation and reveals the underlying
      mechanism for limitations in the reduction of the CdS thickness, even when an
      alkali PDT is applied to the CIGSe absorber.

PMID- 29178777
TI  - Electronic Modulation of Electrocatalytically Active Center of Cu7S4 Nanodisks by
      Cobalt-Doping for Highly Efficient Oxygen Evolution Reaction.
AB  - Cu-based electrocatalysts have seldom been studied for water oxidation because of
      their inferior activity and poor stability regardless of their low cost and
      environmentally benign nature. Therefore, exploring an efficient way to improve
      the activity of Cu-based electrocatalysts is very important for their practical
      application. Modifying electronic structure of the electrocatalytically active
      center of electrocatalysts by metal doping to favor the electron transfer between
      catalyst active sites and electrode is an important approach to optimize hydrogen
      and oxygen species adsorption energy, thus leading to the enhanced intrinsic
      electrocatalytic activity. Herein, Co-doped Cu7S4 nanodisks were synthesized and
      investigated as highly efficient electrocatalyst for oxygen evolution reaction
      (OER) due to the optimized electronic structure of the active center. Density
      functional theory (DFT) calculations reveal that Co-engineered Cu7S4 could
      accelerate electron transfer between Co and Cu sites, thus decrease the energy
      barriers of intermediates and products during OER, which are crucial for enhanced
      catalytic properties. As expected, Co-engineered Cu7S4 nanodisks exhibit a low
      overpotential of 270 mV to achieve current density of 10 mA cm-2 as well as
      decreased Tafel slope and enhanced turnover frequencies as compared to bare
      Cu7S4. This discovery not only provides low-cost and efficient Cu-based
      electrocatalyst by Co doping, but also exhibits an in-depth insight into the
      mechanism of the enhanced OER properties.

PMID- 29178778
TI  - Combinatorial Discovery of Lanthanum-Tantalum Oxynitride Solar Light Absorbers
      with Dilute Nitrogen for Solar Fuel Applications.
AB  - Oxynitrides with the photoelectrochemical stability of oxides and desirable band
      energetics of nitrides comprise a promising class of materials for solar
      photochemistry. Challenges in synthesizing a wide variety of oxynitride materials
      has limited exploration of this class of functional materials, which we address
      using a reactive cosputtering combined with rapid thermal processing method to
      synthesize multi-cation-multi-anion libraries. We demonstrate the synthesis of a
      LaxTa1-xOyNz thin film composition spread library and its characterization by
      both traditional thin film materials characterization and custom combinatorial
      optical spectroscopy and X-ray absorption near edge spectroscopy (XANES)
      techniques, ultimately establishing structure-chemistry-property relationships.
      We observe that over a substantial La-Ta composition range the thin films
      crystallize in the same perovskite LaTaON2 structure with significant variation
      of anion chemistry. The relative invariance in optical band gap demonstrates a
      remarkable decoupling of composition and band energetics so that the composition
      can be optimized while retaining the desirable 2 eV band gap energy. We also
      demonstrate the intercalation of diatomic nitrogen into the La3TaO7 structure,
      which gives rise to a direct-allowed optical transition at 2.2 eV, less than half
      the value of the oxide's band gap. These findings motivate further exploration of
      the visible light response of this material that is predicted to be stable over a
      wide range of electrochemical potential.

PMID- 29178779
TI  - Synthesis of bis-Phosphate Iminoaltritol Enantiomers and Structural
      Characterization with Adenine Phosphoribosyltransferase.
AB  - Phosphoribosyl transferases (PRTs) are essential in nucleotide synthesis and
      salvage, amino acid, and vitamin synthesis. Transition state analysis of several
      PRTs has demonstrated ribocation-like transition states with a partial positive
      charge residing on the pentose ring. Core chemistry for synthesis of transition
      state analogues related to the 5-phospho-alpha-d-ribosyl 1-pyrophosphate (PRPP)
      reactant of these enzymes could be developed by stereospecific placement of bis
      phosphate groups on an iminoaltritol ring. Cationic character is provided by the
      imino group and the bis-phosphates anchor both the 1- and 5-phosphate binding
      sites. We provide a facile synthetic path to these molecules. Cyclic-nitrone
      redox methodology was applied to the stereocontrolled synthesis of three
      stereoisomers of a selectively monoprotected diol relevant to the synthesis of
      transition-state analogue inhibitors. These polyhydroxylated pyrrolidine natural
      product analogues were bis-phosphorylated to generate analogues of the
      ribocationic form of 5-phosphoribosyl 1-phosphate. A safe, high yielding
      synthesis of the key intermediate represents a new route to these transition
      state mimics. An enantiomeric pair of iminoaltritol bis-phosphates (L-DIAB and D
      DIAB) was prepared and shown to display inhibition of Plasmodium falciparum
      orotate phosphoribosyltransferase and Saccharomyces cerevisiae adenine
      phosphoribosyltransferase (ScAPRT). Crystallographic inhibitor binding analysis
      of L- and D-DIAB bound to the catalytic sites of ScAPRT demonstrates
      accommodation of both enantiomers by altered ring geometry and bis-phosphate
      catalytic site contacts.

PMID- 29178780
TI  - Extraordinary Effects in Quasi-Periodic Gold Nanocavities: Enhanced Transmission
      and Polarization Control of Cavity Modes.
AB  - Plasmonic quasi-periodic structures are well-known to exhibit several surprising
      phenomena with respect to their periodic counterparts, due to their long-range
      order and higher rotational symmetry. Thanks to their specific geometrical
      arrangement, plasmonic quasi-crystals offer unique possibilities in tailoring the
      coupling and propagation of surface plasmons through their lattice, a scenario in
      which a plethora of fascinating phenomena can take place. In this paper we
      investigate the extraordinary transmission phenomenon occurring in specifically
      patterned Thue-Morse nanocavities, demonstrating noticeable enhanced
      transmission, directly revealed by near-field optical experiments, performed by
      means of a scanning near-field optical microscope (SNOM). SNOM further provides
      an intuitive picture of confined plasmon modes inside the nanocavities and
      confirms that localization of plasmon modes is based on size and depth of
      nanocavities, while cross talk between close cavities via propagating plasmons
      holds the polarization response of patterned quasi-crystals. Our performed
      numerical simulations are in good agreement with the experimental results. Thus,
      the control on cavity size and incident polarization can be used to alter the
      intensity and spatial properties of confined cavity modes in such structures,
      which can be exploited in order to design a plasmonic device with customized
      optical properties and desired functionalities, to be used for several
      applications in quantum plasmonics.

PMID- 29178781
TI  - Kinetics and Chemistry of Hydrolysis of Ultrathin, Thermally Grown Layers of
      Silicon Oxide as Biofluid Barriers in Flexible Electronic Systems.
AB  - Flexible electronic systems for bioimplants that offer long-term (multidecade)
      stability and safety in operation require thin, biocompatible layers that can
      prevent biofluid penetration. Recent work shows that ultrathin films of silicon
      dioxide thermally grown (TG-SiO2) on device-grade silicon wafers and then
      released as transferrable barriers offer a remarkable set of attributes in this
      context. This paper examines the chemical stability of these materials in aqueous
      solutions with different combinations of chemistries that are present in
      biofluids. Systematic measurements reveal the dependence of the dissolution rate
      of TG-SiO2 on concentrations of cations (Na+, K+, Mg2+, Ca2+) and anions (Cl-,
      HPO42-) at near-neutral pH. Certain results are consistent with previous studies
      on bulk samples of quartz and nanoparticles of amorphous silica; others reveal
      significant catalyzing effects associated with divalent cations at high pH and
      with specific anions at high ionic strength. In particular, Ca2+ and HPO42-
      greatly enhance and silicic acid greatly reduces the rates. These findings
      establish foundational data of relevance to predicting lifetimes of implantable
      devices that use TG-SiO2 as biofluid barriers, and of other classes of systems,
      such as environmental monitors, where encapsulation against water penetration is
      important.

PMID- 29178782
TI  - Aggregation-Induced Fluorescence-to-Phosphorescence Switching of Molecular Gold
      Clusters.
AB  - Aggregation-induced optical responses are ubiquitous among a wide range of
      organic and inorganic compounds. Here, we demonstrate an unprecedented effect of
      aggregation on the photoluminescence (PL) profiles of [core + exo]-type [Au8]4+
      clusters, which displayed a change in the dominant PL emission mode from
      fluorescence to phosphorescence-type upon aggregation. In solvents in which
      cluster molecules are highly soluble and exist as monomers, they displayed single
      PL bands at ~600 nm at ambient temperatures. However, in solvents in which
      cluster molecules are less soluble and cluster aggregation is induced, a new PL
      band at ~700 nm also emerged. Lifetime measurements revealed that the PL
      emissions at ~600 and ~700 nm had fluorescence and phosphorescence characters,
      respectively. Studies of the excitation spectra suggested that organized cluster
      assemblies were responsible for the lower-energy emission at ~700 nm and had
      exceptionally high emission activity. Accordingly, intense phosphorescence-type
      emissions were observed in the solid state in which the quantum efficiencies were
      higher by two orders of magnitude than those of the corresponding monomeric forms
      in solution. This work provides an example of the critical effects of cluster
      aggregation events on their optical properties and shows the potential of such
      effects in the design of cluster-based materials with unique functions and
      properties.

PMID- 29178783
TI  - Heterogeneous Catalysis "On Demand": Mechanically Controlled Catalytic Activity
      of a Metal Surface.
AB  - A metal surface passivated with a tightly packed self-assembled monolayer (SAM)
      can be made catalytically active upon the metal's mechanical deformation. This
      deformation renders the SAM sparser and exposes additional catalytic sites on the
      metal's surface. If the deformation is elastic, return of the metal to the
      original shape "heals" the SAM and nearly extinguishes the catalytic activity.
      Kelvin probe force microscopy and theoretical considerations both indicate that
      the catalytic domains "opening up" in the deformed SAM are of nanoscopic
      dimensions.

PMID- 29178784
TI  - Differential Compound Prioritization via Bidirectional Selectivity Push with
      Power.
AB  - Effective in silico compound prioritization is a critical step to identify
      promising drug candidates in the early stages of drug discovery. Current
      computational methods for compound prioritization usually focus on ranking the
      compounds based on one property, typically activity, with respect to a single
      target. However, compound selectivity is also a key property which should be
      deliberated simultaneously so as to minimize the likelihood of undesired side
      effects of future drugs. In this paper, we present a novel machine-learning based
      differential compound prioritization method dCPPP. This dCPPP method learns
      compound prioritization models that rank active compounds well, and meanwhile,
      preferably rank selective compounds higher via a bidirectional selectivity push
      strategy. The bidirectional push is enhanced by push powers that are determined
      by ranking difference of selective compounds over multiple bioassays. Our
      experiments demonstrate that the new method dCPPP achieves significant
      improvement on prioritizing selective compounds over baseline models.

PMID- 29178785
TI  - Highly Selective and Potent alpha4beta2 nAChR Antagonist Inhibits Nicotine Self
      Administration and Reinstatement in Rats.
AB  - The alpha4beta2 nAChR is the most predominant subtype in the brain and is a well
      known culprit for nicotine addiction. Previously we presented a series of
      alpha4beta2 nAChR selective compounds that were discovered from a mixture-based
      positional-scanning combinatorial library. Here we report further optimization
      identified highly potent and selective alpha4beta2 nAChR antagonists 5 (AP-202)
      and 13 (AP-211). Both compounds are devoid of in vitro agonist activity and are
      potent inhibitors of epibatidine-induced changes in membrane potential in cells
      containing alpha4beta2 nAChR, with IC50 values of approximately 10 nM, but are
      weak agonists in cells containing alpha3beta4 nAChR. In vivo studies show that 5
      can significantly reduce operant nicotine self-administration and nicotine
      relapse-like behavior in rats at doses of 0.3 and 1 mg/kg. The pharmacokinetic
      data also indicate that 5, via sc administration, is rapidly absorbed into the
      blood, reaching maximal concentration within 10 min with a half-life of less than
      1 h.

PMID- 29178786
TI  - Chemoselective SN2' Allylations of Detrifluoroacetylatively In Situ Generated 3
      Fluoroindolin-2-one-Derived Tertiary Enolates with Morita-Baylis-Hillman
      Carbonates.
AB  - The first example of the SN2' reaction type of the detrifluoroacetylatively in
      situ generated tertiary fluoro-enolates in the uncatalyzed reactions with Morita
      Baylis-Hillman derivatives has been described. The SN2' substitution takes place
      in a highly chemoselective manner as no corresponding SN2 products were observed
      in the reaction mixtures. Due to the excellent stereochemical outcome, the
      reactions seem to have an apparent synthetic value for the preparation of
      structurally new fluorinated oxindoles.

PMID- 29178787
TI  - Inter-Enzyme Allosteric Regulation of Chorismate Mutase in Corynebacterium
      glutamicum: Structural Basis of Feedback Activation by Trp.
AB  - Corynebacterium glutamicum is widely used for the industrial production of amino
      acids, nucleotides, and vitamins. The shikimate pathway enzymes DAHP synthase
      (CgDS, Cg2391) and chorismate mutase (CgCM, Cgl0853) play a key role in the
      biosynthesis of aromatic compounds. Here we show that CgCM requires the formation
      of a complex with CgDS to achieve full activity, and that both CgCM and CgDS are
      feedback regulated by aromatic amino acids binding to CgDS. Kinetic analysis
      showed that Phe and Tyr inhibit CgCM activity by inter-enzyme allostery, whereas
      binding of Trp to CgDS strongly activates CgCM. Mechanistic insights were gained
      from crystal structures of the CgCM homodimer, tetrameric CgDS, and the
      heterooctameric CgCM-CgDS complex, refined to 1.1, 2.5, and 2.2 A resolution,
      respectively. Structural details from the allosteric binding sites reveal that
      DAHP synthase is recruited as the dominant regulatory platform to control the
      shikimate pathway, similar to the corresponding enzyme complex from Mycobacterium
      tuberculosis.

PMID- 29178788
TI  - Copper-Catalyzed Coupling of Acyl Chlorides with gem-Difluorinated Organozinc
      Reagents via Acyl Dithiocarbamates.
AB  - A cross-coupling of acyl chlorides with gem-difluorinated organozinc reagents
      affording difluorinated ketones is described. In the reaction, acyl chlorides are
      first treated with potassium dithiocarbamate to generate S-acyl dithiocarbamates,
      which couple with organozincs in the presence of a copper(I) catalyst.

PMID- 29178791
TI  - List of Colleagues, Coauthors and Coworkers of Jorn Manz.

PMID- 29178789
TI  - Chelator-Free Labeling of Metal Oxide Nanostructures with Zirconium-89 for
      Positron Emission Tomography Imaging.
AB  - Radiolabeling of molecules or nanoparticles to form imaging probes is critical
      for positron emission tomography (PET) imaging, which, with high sensitivity and
      the ability for quantitative imaging, has been widely used in the clinic. While
      conventional radiolabeling often employs chelator molecules, a general method for
      chelator-free radiolabeling of a wide range of materials remains to be developed.
      Herein, we determined that 10 different types of metal oxide (MxOy, M = Gd, Ti,
      Te, Eu, Ta, Er, Y, Yb, Ce, or Mo, x = 1-2, y = 2-5) nanomaterials with
      polyethylene glycol (PEG) modification could be labeled with 89Zr, a PET tracer,
      via a simple yet general chelator-free radiolabeling method upon simple mixing.
      High-labeling yields and good serum stabilities are achieved with this method,
      owing to the strong bonding between oxyphilic 89Zr4+ with oxygen atoms on the
      MxOy surface. Selecting 89Zr-Gd2O3-PEG as a multimodal imaging probe, we have
      successfully demonstrated in vivo PET imaging of draining lymph nodes, which are
      also visualized under magnetic resonance imaging, showing advantages over free
      89Zr in the mapping of draining lymph node networks. Our work describes a general
      and simple method for chelator-free radiolabeling of metal oxide nanostructures,
      which is promising for the development of multifunctional nanoprobes in
      biomedical imaging.

PMID- 29178790
TI  - Publications of Jorn Manz.

PMID- 29178792
TI  - Curriculum Vitae of Jorn Manz.

PMID- 29178793
TI  - Symmetry Effects on Attenuation Factors in Graphene-Based Molecular Junctions.
AB  - The unique structural and electronic characteristics of graphene make it an
      attractive contact for fundamental single-molecule electrical studies. With this
      in mind, we have probed here the electrical conductance of a molecular junction
      based on alpha,omega-diaminoalkane chains sandwiched between a gold and a
      graphene electrode. Using an STM based I(s) method combined with density
      functional theory-based transport calculations, we demonstrate that the resulting
      attenuation factor turns out to be much lower when compared to the standard
      molecular junction between two gold electrodes. This effect is attributed to
      asymmetric coupling of the molecule through strong chemisorption at the gold
      electrode and weaker van der Waals contact at graphene. Moreover, this asymmetric
      coupling induces higher conductance than that in the same hybrid metal-graphene
      molecular junction using standard thiol anchoring groups.

PMID- 29178794
TI  - Polarizable Density Embedding: A Solution to the Electron Spill-Out Problem in
      Multiscale Modeling.
AB  - We analyze the performance of the polarizable density embedding (PDE) model-a new
      multiscale computational approach designed for prediction and rationalization of
      general molecular properties of large and complex systems. We showcase how the
      PDE model very effectively handles the use of large and diffuse basis sets that
      are otherwise questionable-due to electron spill-out effects-in standard
      embedding models. Based on our analysis, we find the PDE model to be robust and
      much more systematic than less sophisticated focused embedding models, and thus
      outline the PDE model as a very efficient and accurate approach to describe the
      electronic structure of ground and excited states as well as molecular properties
      of complex, heterogeneous systems.

PMID- 29178795
TI  - Accelerating Turnover Frequency in Nucleic Acid Templated Reactions.
AB  - Nucleic acid templated reactions have attracted attention as an important
      technology to sense oligonucleotides and to translate nucleic acid-based
      instructions into diverse outputs. Great progress has been made in accelerating
      the reaction in order to improve signal amplification, reaching rates where
      substrate turnover rather than chemical reaction is rate limiting. Herein we
      explore the utility of architectures inspired by three-way junction that yield a
      cleavage of a strand thus accelerating substrate turnover. We demonstrate that
      such design can overcome product inhibition in templated reactions and operate
      close to the rate of hybridization.

PMID- 29178796
TI  - Protein Nanopore-Based Discrimination between Selected Neutral Amino Acids from
      Polypeptides.
AB  - Nanopore probing of biological polymers has the potential to achieve single
      molecule sequencing at low cost, high throughput, portability, and minimal sample
      preparation and apparatus. In this article, we explore the possibility of
      discrimination between neutral amino acid residues from the primary structure of
      30 amino acids long, engineered peptides, through the analysis of single-molecule
      ionic current fluctuations accompanying their slowed-down translocation across
      the wild type alpha-hemolysin (alpha-HL) nanopore, and molecular dynamics
      simulations. We found that the transient presence inside the alpha-HL of alanine
      or tryptophan residues from the primary sequence of engineered peptides results
      in distinct features of the ionic current fluctuation pattern associated with the
      peptide reversibly blocking the nanopore. We propose that alpha-HL sensitivity to
      the molecular exclusion at the most constricted region mediates ionic current
      blockade events correlated with the volumes that are occluded by at least three
      alanine or tryptophan residues, and provides the specificity needed to
      discriminate between groups of neutral amino acids. Further, we find that the
      pattern of current fluctuations depends on the orientation of the threaded amino
      acid residues, suggestive of a conformational anisotropy of the ensemble of
      conformations of the peptide on the restricted nanopore region, related to its
      relative axial orientation inside the nanopore.

PMID- 29178797
TI  - Unprotected Indazoles Are Resilient to Ring-Opening Isomerization: A Case Study
      on Catalytic C-S Couplings in the Presence of Strong Base.
AB  - Indazoles represent a privileged scaffold in medicinal chemistry. In the presence
      of strong base, however, N-protected indazoles are prone to an undesirable ring
      opening reaction to liberate o-aminobenzonitriles. By employing unprotected
      indazoles with a free N-H bond, isomerization is averted because the heterocycle
      is deprotonated in situ. We herein report functional group-tolerant and robust C
      S couplings of bromoindazoles with thiols of varying electronic nature in the
      presence of lithium bis(trimethylsilyl)amide at elevated temperatures.

PMID- 29178799
TI  - Cryptophanes for Methane and Xenon Encapsulation: A Comparative Density
      Functional Theory Study of Binding Properties and NMR Chemical Shifts.
AB  - The host-guest chemistry of cryptophanes is an active research area because of
      its applications in sensor design, targeting small molecules and atoms in
      environmental and medical sciences. As such, the computational prediction of
      binding energies and nuclear magnetic resonance (NMR) properties of different
      cryptophane complexes are of interest to both theoreticians and experimentalists
      working in host-guest based sensor development. Herein we present a study of 10
      known and some newly proposed cryptophanes using density functional theory (DFT)
      calculations. We benchmark the description of nonbonding interactions by
      different DFT functionals against spin-component-scaled, second-order Moller
      Plesset theory (SCS-MP2) and predict novel host molecules with enhanced affinity
      toward methane and Xenon, two representative systems of high interest. We
      demonstrate the power and limitations of the different computational methods in
      describing the binding and NMR properties of these established and novel host
      systems. The results show the importance of including dispersion corrections in
      the DFT functionals. The overall analysis of the dispersion corrections indicated
      that results obtained from pure DFT functionals should be used cautiously when
      conclusions are drawn for molecular systems with considerable weak interactions.
      Proposed analogues of cryptophane-A, where the alkoxy bridges are replaced by
      alkyl chains, are predicted to display enhanced affinity toward both methane and
      Xenon.

PMID- 29178798
TI  - Dissolution of Monocrystalline Silicon Nanomembranes and Their Use as
      Encapsulation Layers and Electrical Interfaces in Water-Soluble Electronics.
AB  - The chemistry that governs the dissolution of device-grade, monocrystalline
      silicon nanomembranes into benign end products by hydrolysis serves as the
      foundation for fully eco/biodegradable classes of high-performance electronics.
      This paper examines these processes in aqueous solutions with chemical
      compositions relevant to groundwater and biofluids. The results show that the
      presence of Si(OH)4 and proteins in these solutions can slow the rates of
      dissolution and that ion-specific effects associated with Ca2+ can significantly
      increase these rates. This information allows for effective use of silicon
      nanomembranes not only as active layers in eco/biodegradable electronics but also
      as water barriers capable of providing perfect encapsulation until their
      disappearance by dissolution. The time scales for this encapsulation can be
      controlled by introduction of dopants into the Si and by addition of oxide layers
      on the exposed surfaces.The former possibility also allows the doped silicon to
      serve as an electrical interface for measuring biopotentials, as demonstrated in
      fully bioresorbable platforms for in vivo neural recordings. This collection of
      findings is important for further engineering development of water-soluble
      classes of silicon electronics.

PMID- 29178800
TI  - Natural Attenuation and Anaerobic Benzene Detoxification Processes at a
      Chlorobenzene-Contaminated Industrial Site Inferred from Field Investigations and
      Microcosm Studies.
AB  - A five-year site investigation was conducted at a former chemical plant in
      Nanjing, China. The main contaminants were 1,2,4-trichlorobenzene (TCB) reaching
      concentrations up to 7300 MUg/L, dichlorobenzene (DCB) isomers, monochlorobenzene
      (MCB), and benzene. Over time, these contaminants naturally attenuated to below
      regulatory levels under anaerobic conditions. To confirm the transformation
      processes and to explore the mechanisms, a corresponding laboratory microcosm
      study was completed demonstrating that 1,2,4-TCB was dechlorinated to 1,2-DCB,
      1,3-DCB, and 1,4-DCB in approximately 2%/10%/88% molar proportions. The DCB
      isomers were dechlorinated via MCB to benzene, and, finally, benzene was degraded
      under prevailing sulfate-reducing conditions. Dechlorination could not be
      attributed to known dechlorinators Dehalobacter or Dehalococcoides, while
      anaerobic benzene degradation was mediated by microbes affiliated to a
      Deltaproteobacterium ORM2, previously associated with this activity. Unidentified
      organic compounds, possibly aromatic compounds related to past on-site production
      processes, were fueling the dechlorination reactions in situ. The microcosm study
      confirmed transformation processes inferred from field data and provided needed
      assurance for natural attenuation. Activity-based microcosm studies are often
      omitted from site characterization in favor of rapid and less expensive molecular
      surveys. However, the value of microcosm studies for confirming transformation
      processes, establishing electron balances, assessing cocontaminant inhibition,
      and validating appropriate monitoring tools is clear. At complex sites impacted
      by multiple compounds with poorly characterized transformation mechanisms,
      activity assays provide valuable data to incorporate into the conceptual site
      model to most effectively inform remediation alternatives.

PMID- 29178801
TI  - Absolute Energy Level Positions in CdSe Nanostructures from Potential-Modulated
      Absorption Spectroscopy (EMAS).
AB  - Semiconductor nanostructures such as CdSe quantum dots and colloidal
      nanoplatelets exhibit remarkable optical properties, making them interesting for
      applications in optoelectronics and photocatalysis. For both areas of application
      a detailed understanding of the electronic structure is essential to achieve
      highly efficient devices. The electronic structure can be probed using the fact
      that optical properties of semiconductor nanoparticles are found to be extremely
      sensitive to the presence of excess charges that can for instance be generated by
      means of an electrochemical charge transfer via an electrode. Here we present the
      use of EMAS as a versatile spectroelectrochemical method to obtain absolute band
      edge positions of CdSe nanostructures versus a well-defined reference electrode
      under ambient conditions. In this, the spectral properties of the nanoparticles
      are monitored with respect to an applied electrochemical potential. We developed
      a bleaching model that yields the lowest electronic state in the conduction band
      of the nanostructures. A change in the band edge positions caused by quantum
      confinement is shown both for CdSe quantum dots and for colloidal nanoplatelets.
      In the case of CdSe quantum dots these findings are in good agreement with tight
      binding calculations. The method presented is not limited to CdSe nanostructures
      but can be used as a universal tool. Hence, this technique allows the
      determination of absolute band edge positions of a large variety of materials
      used in various applications.

PMID- 29178802
TI  - Rotamer-Specific Photoisomerization of Difluorostilbenes from Transient
      Absorption and Transient Raman Spectroscopy.
AB  - Photoisomerization of 2,2'-, 3,3'-, and 4,4'-difluorostilbene (F2, F3, F4,
      respectively) in n-hexane, perfluoro-n-hexane, and acetonitrile is studied with
      broadband transient absorption (TA) and femtosecond stimulated Raman (FSR)
      spectroscopy and by DFT/TDDFT calculations. F2 and F3 possess three rotamers
      (rotational isomers) each, while F4 has one single conformation only. These
      differences are reflected in TA and FSR spectra. Thus F4 reveals a
      monoexponential decay of TA with tau1 = 172 ps in n-hexane, as expected for a
      single species. For F2 and F3, the decays are biexponential in all solvents,
      corresponding to two distinctly discerned rotamers or rotamer fractions.
      Specifically, for F2 in n-hexane, tau1 = 357 ps (83%) and tau2 = 62 ps (17%), and
      for F3 in the same solvent, tau1 = 222 ps (57%), and tau2 = 81 ps (43%). The
      weights in brackets agree with theoretically estimated ground-state abundances of
      the rotamers. Furthermore, a global fit of the TA and FSR data allows us to
      extract the spectra of the pure rotamers. The Raman spectra of S0 and S1 are in
      qualitative agreement with calculations.

PMID- 29178803
TI  - NMR Chemical Shift of a Helium Atom as a Probe for Electronic Structure of FH, F
      , (FHF)-, and FH2.
AB  - In this work, we present the first results of outer electronic shell
      visualization by using a 3He atom as a probe particle. As model objects we have
      chosen F-, FH, and FH2+ species, as well as the hydrogen-bonded complex FH...F-
      at various H...F- distances (3.0, 2.5, 2.0, and 1.5 A and equilibrium at ca. 1.14
      A). The interaction energy of investigated objects with helium atom (CCSD/aug-cc
      pVTZ) and helium atom chemical shift (B3LYP/pcS-2) surfaces were calculated, and
      their topological analysis was performed. For comparison, the results of standard
      quantum mechanical approaches to electronic shell visualization were presented
      (ESP, ELF, ED, ?2ED). We show that the Laplacian of helium chemical shift,
      ?2deltaHe, is sensitive to fluorine atom lone pair localization regions, and it
      can be used for the visualization of the outer electronic shell, which could be
      used to evaluate the proton accepting ability. The sensitivity of ?2deltaHe to
      lone pairs is preserved at distances as large as 2.0-2.5 A from the fluorine
      nucleus (in comparison with the distance to ESP minima, located at 1.0-1.5 A or
      maxima of ELF, which are as close as 0.6 A to the fluorine nucleus).

PMID- 29178804
TI  - Nanoporosity Change on Elastic Relaxation of Partially Folded Graphene Monoliths.
AB  - Fabrication of nanographene shows a promising route for production of designed
      porous carbons, which is indispensable for highly efficient molecular separation
      and energy storage applications. This process requires a better understanding of
      the mechanical properties of nanographene in their aggregated structure. We
      studied the structural and mechanical properties of nanographene monoliths
      compressed at 43 MPa over different times from 3 to 25 h. While in monoliths
      compressed over shorter time adsorption isotherms of Ar at 87 K or N2 at 77 K
      exhibited a prominent hysteresis due to presence of predominant mesopores,
      compression for long time induces a low pressure hysteresis. On the other hand,
      compression for 25 h increases the microporosity evaluated by Ar adsorption, not
      by N2 adsorption, indicating that 25 h compression rearranges the nanographene
      stacking structure to produce ultramicropores that can be accessible only for Ar.
      TEM, X-ray diffraction, and Raman spectroscopic studies indicated that the
      compression for 25 h unfolds double-bent-like structures, relaxing the unstable
      nanographene stacked structure formed on the initial compression without
      nanographene sheets collapse. This behavior stems from the highly elastic nature
      of the nanographenes.

PMID- 29178805
TI  - Zn2+ Induced Irreversible Aggregation, Stacking, and Leakage of Choline Phosphate
      Liposomes.
AB  - The interaction between lipids and metal ions is important for metal sensing,
      cellular signal transduction, and oxidative lipid damage. While most previous
      work overlooked the phosphate group of lipids for metal binding, we herein
      highlight its importance. Phosphocholine (PC) and its headgroup inversed choline
      phosphate (CP) lipids were used to prepare liposomes. From dynamic light
      scattering (DLS), Zn2+ causes significant aggregation or fusion of the CP
      liposomes, but not PC liposomes. The size change induced by Zn2+ is not fully
      reversed by adding EDTA, implying liposome fusion induced by Zn2+. Isothermal
      titration calorimetry (ITC) shows that binding between Zn2+ and CP liposomes is
      endothermic with a Kd of 110 MUM Zn2+, suggesting an entropy driven reaction
      likely due to the release of bound water. In comparison, no heat was detected by
      titrating Zn2+ into PC liposomes or Ca2+ into CP liposomes. Furthermore, Zn2+
      causes a transient leakage of the CP liposomes, and further leakage is observed
      upon removing Zn2+ by EDTA. Transmission electron microscopy (TEM) with negative
      stained samples showed multilamellar CP lipid structures attributable to Zn2+
      sandwiched between lipid bilayers, leading to a proposed reaction mechanism. This
      work provides an interesting system for studying metal interacting with terminal
      phosphate groups in liposomes, affecting the size, charge, and membrane integrity
      of the liposomes.

PMID- 29178806
TI  - Ligand-Assisted, One-Pot Synthesis of Rh-on-Cu Nanoscale Sea Urchins with High
      Density Interfaces for Boosting CO Oxidation.
AB  - Predictable synthesis of bimetallic nanocrystals with spatially controlled metal
      distributions offers a versatile route to the development of highly efficient
      nanocatalysts. Here we report a one-pot synthesis of super branched Rh-on-Cu
      nanoscale sea urchins (Rh-Cu NSUrs) with a high density of Cu-Rh interfaces by
      manipulating the ligand coordination chemistry. Structural analysis and UV-vis
      spectra reveal that ascorbic acid can serve as a Rh-selective coordination ligand
      in the nonaqueous synthesis to reverse the reduction potentials of Rh3+ and Cu2+
      cations. The sequential reduction of Cu2+ and then Rh3+ cations, as well as the
      island epitaxial growth of Rh atoms on Cu cores, leads to the formation of Rh-on
      Cu nanostructures mimicking sea urchin. The size of the Cu cores and the density
      of Rh branches can both be facilely regulated by tuning the mole ratio of Cu to
      Rh. The Cu-Rh NSUrs show enhanced activity and stability in catalyzing CO
      oxidation, as the intrinsic Cu-Rh interfaces can act as catalytic hot spots
      through a bifunctional mechanism. The Cu-Rh two-component system can separate the
      adsorption and activation of CO and O2 on the Rh and Cu surfaces, respectively,
      accelerating the generation of CO2 at the interfaces.

PMID- 29178807
TI  - Conductive Tungsten Oxide Nanosheets for Highly Efficient Hydrogen Evolution.
AB  - Exploring efficient and economical electrocatalysts for hydrogen evolution
      reaction is of great significance for water splitting on an industrial scale.
      Tungsten oxide, WO3, has been long expected to be a promising non-precious-metal
      electrocatalyst for hydrogen production. However, the poor intrinsic activity of
      this material hampers its development. Herein, we design a highly efficient
      hydrogen evolution electrocatalyst via introducing oxygen vacancies into WO3
      nanosheets. Our first-principles calculations demonstrate that the gap states
      introduced by O vacancies make WO3 act as a degenerate semiconductor with high
      conductivity and desirable hydrogen adsorption free energy. Experimentally, we
      prepared WO3 nanosheets rich in oxygen vacancies via a liquid exfoliation, which
      indeed exhibits the typical character of a degenerate semiconductor. When
      evaluated by hydrogen evolution, the nanosheets display superior performance with
      a small overpotential of 38 mV at 10 mA cm-2 and a low Tafel slope of 38 mV dec
      1. This work opens an effective route to develop conductive tungsten oxide as a
      potential alternative to the state-of-the-art platinum for hydrogen evolution.

PMID- 29178808
TI  - Self-Assembled Porous Alumina Based Organic Nanotriode Arrays.
AB  - We utilize ordered mesoporous alumina templates for solution processable
      electronics and demonstrate massively parallel organization of connected three
      terminal vertical transistors. The vertical transistor device consists of a
      connected organic nanotriode array obtained using porous anodized alumina
      membranes of pore density ~ 109 pores/cm2. In this structure, a collector-emitter
      diode gives rise to a space charge limited current, which can be controlled by a
      third intermediate porous base electrode to give transistor-like characteristics.
      We study the response characteristics along with 2D device simulations of this
      novel structure to indicate key parameters involved in the underlying mechanism.
      Device operation at single transistor level is verified by conductive atomic
      force microscopy, and the inherent short switching time scales of the vertical
      structure device is also demonstrated.

PMID- 29178809
TI  - Quantum Confinement of Hybrid Charge Transfer Excitons in GaN/InGaN/Organic
      Semiconductor Quantum Wells.
AB  - We investigate hybrid charge transfer exciton (HCTE) confinement in organic
      inorganic (OI) quantum wells (QWs) comprising a thin InGaN layer bound on one
      side by GaN and on the other by the organic semiconductors,
      tetraphenyldibenzoperiflanthene (DBP) or 4,4'-bis(N-carbazolyl)-1,1'-biphenyl
      (CBP). A binding energy of 10 meV is calculated for the Coulombically bound free
      HCTE state between a delocalized electron in GaN and a hole localized in DBP. The
      binding energy of the HCTE increases to 165 meV when the electron is confined to
      a 1.5 nm In0.21Ga0.79N QW (HCTEQW). The existence of the HCTEQW is confirmed by
      measuring the voltage-dependent DBP exciton dissociation yield at the OI
      heterojunction in the QW devices that decrease with increasing In concentration
      and decreasing electric field, matching the trends predicted by Poole-Frenkel
      emission. Combining spectroscopic measurements with optical models, we find that
      14 +/- 3% of the excitons that reach the GaN/DBP heterojunction form HCTEs and
      dissociate into free charges, while the remainder recombine. A high nonradiative
      recombination rate through defect states at the heterointerface account for the
      lack of observation of HCTEQW photoluminescence from GaN/InGaN/CBP QWs at
      temperatures as low as 10 K.

PMID- 29178810
TI  - Nanoscale-Agglomerate-Mediated Heterogeneous Nucleation.
AB  - Water vapor condensation on hydrophobic surfaces has received much attention due
      to its ability to rapidly shed water droplets and enhance heat transfer, anti
      icing, water harvesting, energy harvesting, and self-cleaning performance.
      However, the mechanism of heterogeneous nucleation on hydrophobic surfaces
      remains poorly understood and is attributed to defects in the hydrophobic coating
      exposing the high surface energy substrate. Here, we observe the formation of
      high surface energy nanoscale agglomerates on hydrophobic coatings after
      condensation/evaporation cycles in ambient conditions. To investigate the
      deposition dynamics, we studied the nanoscale agglomerates as a function of
      condensation/evaporation cycles via optical and field emission scanning electron
      microscopy (FESEM), microgoniometric contact angle measurements, nucleation
      statistics, and energy dispersive X-ray spectroscopy (EDS). The FESEM and EDS
      results indicated that the nanoscale agglomerates stem from absorption of
      sulfuric acid based aerosol particles inside the droplet and adsorption of
      volatile organic compounds such as methanethiol (CH3SH), dimethyl disulfide
      (CH3SSCH), and dimethyl trisulfide (CH3SSSCH3) on the liquid-vapor interface
      during water vapor condensation, which act as preferential sites for
      heterogeneous nucleation after evaporation. The insights gained from this study
      elucidate fundamental aspects governing the behavior of both short- and long-term
      heterogeneous nucleation on hydrophobic surfaces, suggest previously unexplored
      microfabrication and air purification techniques, and present insights into the
      challenges facing the development of durable dropwise condensing surfaces.

PMID- 29178812
TI  - Word Processing in Scene Context: An Event-Related Potential Study in Young
      Children.
AB  - Semantic priming has been demonstrated in object or word contexts in toddlers.
      However, less is known about semantic priming in scene context. In this study, 24
      month-olds with high and low vocabulary skills were presented with visual scenes
      (e.g., kitchen) followed by semantically consistent (e.g., spoon) or inconsistent
      (e.g., bed) spoken words. Inconsistent scene-word pairs evoked a larger N400
      component over the frontal areas. Low-producers presented a larger N400 over the
      right while high-producers over the left frontal areas. Our results suggest that
      contextual information facilitates word processing in young children.
      Additionally, children with different linguistic skills activate different neural
      structures.

PMID- 29178813
TI  - The Threat of Synthetic Smallpox: European Perspectives.
AB  - This article explores how advances in synthetic biology, and the potential threat
      of deliberately recreating and spreading smallpox, are affecting the multilateral
      debate on the remaining variola virus stocks. It draws on in-depth, semi
      structured interviews with 10 high-profile, European-based experts in biosecurity
      and synthetic biology. Four overarching themes affecting the retention or
      destruction debate are discussed, relating to biosecurity, dangerous knowledge,
      accidental releases, and eradication. We conclude that while synthetic biology
      seems to affect all the main discourses in the variola stocks debate, a range of
      views is present and it is not apparent that advances in synthetic biology are
      causing a shift toward either retention or destruction of the stocks.

PMID- 29178811
TI  - Cell-Extracellular Matrix Mechanobiology: Forceful Tools and Emerging Needs for
      Basic and Translational Research.
AB  - Extracellular biophysical cues have a profound influence on a wide range of cell
      behaviors, including growth, motility, differentiation, apoptosis, gene
      expression, adhesion, and signal transduction. Cells not only respond to
      definitively mechanical cues from the extracellular matrix (ECM) but can also
      sometimes alter the mechanical properties of the matrix and hence influence
      subsequent matrix-based cues in both physiological and pathological processes.
      Interactions between cells and materials in vitro can modify cell phenotype and
      ECM structure, whether intentionally or inadvertently. Interactions between cell
      and matrix mechanics in vivo are of particular importance in a wide variety of
      disorders, including cancer, central nervous system injury, fibrotic diseases,
      and myocardial infarction. Both the in vitro and in vivo effects of this coupling
      between mechanics and biology hold important implications for clinical
      applications.

PMID- 29178814
TI  - Natural Hazards Preparedness in Taiwan: A Comparison Between Households With and
      Without Disabled Members.
AB  - People with disabilities are one of the most vulnerable groups to natural
      hazards. Preparedness is critical to protect life and reduce disaster impact.
      This article discusses the knowledge of the disaster preparedness behaviors of
      people with disabilities using updated, representative data from Taiwan (2013
      Taiwan Social Change Survey), with a comparison to households without disabled
      members. The adoption of 6 preparedness activities-relocating vehicles or
      valuable things to a safer place, purchasing insurance, securing furniture,
      preparing an emergency kit, planning evacuation, and participating in drills-are
      used separately as dependent variables. The unadjusted results from Logit
      regression models show that the households with disabled members are less likely
      to prepare emergency kits and to plan evacuation. But with the adjustment of risk
      perception (probability, consequence, worrisome) and other factors-experience of
      earthquake and typhoon hazards, home ownership status, whether there are children
      in the home, perceived social status, family income, gender, age, education
      attainment, and religious status-the differences in adopting all 6 preparedness
      activities between households with disabled members and households without
      disabled members become nonsignificant. Finally, the contribution, limitations,
      and practice implications of this article are discussed.

PMID- 29178815
TI  - Central Core Laboratory versus Site Interpretation of Coronary CT Angiography:
      Agreement and Association with Cardiovascular Events in the PROMISE Trial.
AB  - Purpose To assess concordance and relative prognostic utility between central
      core laboratory and local site interpretation for significant coronary artery
      disease (CAD) and cardiovascular events. Materials and Methods In the Prospective
      Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, readers
      at 193 North American sites interpreted coronary computed tomographic (CT)
      angiography as part of the clinical evaluation of stable chest pain. Readers at a
      central core laboratory also interpreted CT angiography blinded to clinical data,
      site interpretation, and outcomes. Significant CAD was defined as stenosis
      greater than or equal to 50%; cardiovascular events were defined as a composite
      of cardiovascular death or myocardial infarction. Results In 4347 patients (51.8%
      women; mean age +/- standard deviation, 60.4 years +/- 8.2), core laboratory and
      site interpretations were discordant in 16% (683 of 4347), most commonly because
      of a finding of significant CAD by site but not by core laboratory interpretation
      (80%, 544 of 683). Overall, core laboratory interpretation resulted in 41% fewer
      patients being reported as having significant CAD (14%, 595 of 4347 vs 23%, 1000
      of 4347; P < .001). Over a median follow-up period of 25 months, 1.3% (57 of
      4347) sustained myocardial infarction or cardiovascular death. The C statistic
      for future myocardial infarction or cardiovascular death was 0.61 (95% confidence
      interval [CI]: 0.54, 0.68) for the core laboratory and 0.63 (95% CI: 0.56, 0.70)
      for the sites. Conclusion Compared with interpretation by readers at 193 North
      American sites, standardized core laboratory interpretation classified 41% fewer
      patients as having significant CAD. (c) RSNA, 2017 Online supplemental material
      is available for this article. Clinical trial registration no. NCT01174550.

PMID- 29178816
TI  - A Pivotal Study of Optoacoustic Imaging to Diagnose Benign and Malignant Breast
      Masses: A New Evaluation Tool for Radiologists.
AB  - Purpose To compare the diagnostic utility of an investigational optoacoustic
      imaging device that fuses laser optical imaging (OA) with grayscale
      ultrasonography (US) to grayscale US alone in differentiating benign and
      malignant breast masses. Materials and Methods This prospective, 16-site study of
      2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging
      Reporting and Data System (BI-RADS) categories assigned by seven blinded
      independent readers to benign and malignant breast masses using OA/US versus US
      alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven
      histologic findings and BI-RADS 3 masses stable at 12 months were eligible.
      Independent readers reviewed US images obtained with the OA/US device, assigned a
      probability of malignancy (POM) and BI-RADS category, and locked results. The
      same independent readers then reviewed OA/US images, scored OA features, and
      assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were
      calculated for US and OA/US. Benign and malignant mass upgrade and downgrade
      rates, positive and negative predictive values, and positive and negative
      likelihood ratios were compared. Results Of 2105 consented subjects with 2191
      masses, 100 subjects (103 masses) were analyzed separately as a training
      population and excluded. An additional 202 subjects (210 masses) were excluded
      due to technical failures or incomplete imaging, 72 subjects (78 masses) due to
      protocol deviations, and 41 subjects (43 masses) due to high-risk histologic
      results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%]
      malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with
      a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%)
      for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of
      the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI:
      12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99%
      CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P
      < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative
      examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI
      RADS 4B) to a posttest probability of 2% (BI-RADS 3). Conclusion OA/US increases
      the specificity of breast mass assessment compared with the device internal
      grayscale US alone. Online supplemental material is available for this article.
      (c) RSNA, 2017.

PMID- 29178817
TI  - Conditional Degrons for Controlling Protein Expression at the Protein Level.
AB  - The conditional depletion of a protein of interest (POI) is useful not only for
      loss-of-function studies, but also for the modulation of biological pathways.
      Technologies that work at the level of DNA, mRNA, and protein are available for
      temporal protein depletion. Compared with technologies targeting the
      pretranslation steps, direct protein depletion (or protein knockdown approaches)
      is advantageous in terms of specificity, reversibility, and time required for
      depletion, which can be achieved by fusing a POI with a protein domain called a
      degron that induces rapid proteolysis of the fusion protein. Conditional degrons
      can be activated or inhibited by temperature, small molecules, light, or the
      expression of another protein. The conditional degron-based technologies
      currently available are described and discussed.

PMID- 29178818
TI  - Transcriptional Regulation in Archaea: From Individual Genes to Global Regulatory
      Networks.
AB  - Archaea are major contributors to biogeochemical cycles, possess unique metabolic
      capabilities, and resist extreme stress. To regulate the expression of genes
      encoding these unique programs, archaeal cells use gene regulatory networks
      (GRNs) composed of transcription factor proteins and their target genes. Recent
      developments in genetics, genomics, and computational methods used with archaeal
      model organisms have enabled the mapping and prediction of global GRN structures.
      Experimental tests of these predictions have revealed the dynamical function of
      GRNs in response to environmental variation. Here, we review recent progress made
      in this area, from investigating the mechanisms of transcriptional regulation of
      individual genes to small-scale subnetworks and genome-wide global networks. At
      each level, archaeal GRNs consist of a hybrid of bacterial, eukaryotic, and
      uniquely archaeal mechanisms. We discuss this theme from the perspective of the
      role of individual transcription factors in genome-wide regulation, how these
      proteins interact to compile GRN topological structures, and how these topologies
      lead to emergent, high-level GRN functions. We conclude by discussing how systems
      biology approaches are a fruitful avenue for addressing remaining challenges,
      such as discovering gene function and the evolution of GRNs.

PMID- 29178819
TI  - Mas-Related G Protein-Coupled Receptors and the Biology of Itch Sensation.
AB  - Chronic, persistent itch is a devastating symptom that causes much suffering. In
      recent years, there has been great progress made in understanding the molecules,
      cells, and circuits underlying itch sensation. Once thought to be carried by pain
      sensing neurons, itch is now believed to be capable of being transmitted by
      dedicated sensory labeled lines. Members of the Mas-related G protein-coupled
      receptor (Mrgpr) family demarcate an itch-specific labeled line in the peripheral
      nervous system. In the spinal cord, the expression of other proteins identifies
      additional populations of itch-dedicated sensory neurons. However, as evidence
      for labeled-line coding has mounted, studies promoting alternative itch-coding
      strategies have emerged, complicating our understanding of the neural basis of
      itch. In this review, we cover the molecules, cells, and circuits related to
      understanding the neural basis of itch, with a focus on the role of Mrgprs in
      mediating itch sensation.

PMID- 29178820
TI  - Nucleases Acting at Stalled Forks: How to Reboot the Replication Program with a
      Few Shortcuts.
AB  - In a lifetime, a human being synthesizes approximately 2*1016 meters of DNA, a
      distance that corresponds to 130,000 times the distance between the Earth and the
      Sun. This daunting task is executed by thousands of replication forks, which
      progress along the chromosomes and frequently stall when they encounter DNA
      lesions, unusual DNA structures, RNA polymerases, or tightly-bound protein
      complexes. To complete DNA synthesis before the onset of mitosis, eukaryotic
      cells have evolved complex mechanisms to process and restart arrested forks
      through the coordinated action of multiple nucleases, topoisomerases, and
      helicases. In this review, we discuss recent advances in understanding the role
      and regulation of nucleases acting at stalled forks with a focus on the
      nucleolytic degradation of nascent DNA, a process commonly referred to as fork
      resection. We also discuss the effects of deregulated fork resection on genomic
      instability and on the unscheduled activation of the interferon response under
      replication stress conditions.

PMID- 29178821
TI  - Mosaicism in Cutaneous Disorders.
AB  - Genetic mosaicism arises when a zygote harbors two or more distinct genotypes,
      typically due to de novo, somatic mutation during embryogenesis. The clinical
      manifestations largely depend on the differentiation status of the mutated cell;
      earlier mutations target pluripotent cells and generate more widespread disease
      affecting multiple organ systems. If gonadal tissue is spared-as in somatic
      genomic mosaicism-the mutation and its effects are limited to the proband,
      whereas mosaicism also affecting the gametes, such as germline or gonosomal
      mosaicism, is transmissible. Mosaicism is easily appreciated in cutaneous
      disorders, as phenotypically distinct mutant cells often give rise to lesions in
      patterns determined by the affected cell type. Genetic investigation of cutaneous
      mosaic disorders has identified pathways central to disease pathogenesis,
      revealing novel therapeutic targets. In this review, we discuss examples of
      cutaneous mosaicism, approaches to gene discovery in these disorders, and
      insights into molecular pathobiology that have potential for clinical
      translation.

PMID- 29178822
TI  - A modified GC-specific MAKER gene annotation method reveals improved and novel
      gene predictions of high and low GC content in Oryza sativa.
AB  - BACKGROUND: Accurate structural annotation depends on well-trained gene
      prediction programs. Training data for gene prediction programs are often chosen
      randomly from a subset of high-quality genes that ideally represent the variation
      found within a genome. One aspect of gene variation is GC content, which differs
      across species and is bimodal in grass genomes. When gene prediction programs are
      trained on a subset of grass genes with random GC content, they are effectively
      being trained on two classes of genes at once, and this can be expected to result
      in poor results when genes are predicted in new genome sequences. RESULTS: We
      find that gene prediction programs trained on grass genes with random GC content
      do not completely predict all grass genes with extreme GC content. We show that
      gene prediction programs that are trained with grass genes with high or low GC
      content can make both better and unique gene predictions compared to gene
      prediction programs that are trained on genes with random GC content. By
      separately training gene prediction programs with genes from multiple GC ranges
      and using the programs within the MAKER genome annotation pipeline, we were able
      to improve the annotation of the Oryza sativa genome compared to using the
      standard MAKER annotation protocol. Gene structure was improved in over 13% of
      genes, and 651 novel genes were predicted by the GC-specific MAKER protocol.
      CONCLUSIONS: We present a new GC-specific MAKER annotation protocol to predict
      new and improved gene models and assess the biological significance of this
      method in Oryza sativa. We expect that this protocol will also be beneficial for
      gene prediction in any organism with bimodal or other unusual gene GC content.

PMID- 29178823
TI  - Genetic relatedness of Vibrio cholerae isolates within and between households
      during outbreaks in Dhaka, Bangladesh.
AB  - BACKGROUND: Household contacts of cholera patients have a 100 times higher risk
      of developing a cholera infection than the general population. To compare the
      genetic relatedness of clinical and water source Vibrio cholerae isolates from
      cholera patients' households across three outbreaks, we analyzed these isolates
      using whole-genome-sequencing (WGS) and multilocus variable-number tandem-repeat
      analysis (MLVA). RESULTS: The WGS analyses revealed that 80% of households had
      source water isolates that were more closely related to clinical isolates from
      the same household than to any other isolates. While in another 20% of households
      an isolate from a person was more closely related to clinical isolates from
      another household than to source water isolates from their own household. The
      mean pairwise differences in single nucleotide-variant (SNV) counts for isolates
      from the same household were significantly lower than those for different
      households (2.4 vs. 7.7 p < 0.0001), and isolates from the same outbreak had
      significantly fewer mean pairwise differences compared to isolates from different
      outbreaks (mean: 6.2 vs. 8.0, p < 0.0001). Based on MLVA in outbreak 1, we
      observed that the majority of households had clinical isolates with MLVA
      genotypes related to other clinical isolates and unrelated to water source
      isolates from the same household. While in outbreak 3, there were different MLVA
      genotypes between households, however within the majority of households, the
      clinical and water source isolates had the same MLVA genotypes. The beginning of
      outbreak 2 resembled outbreak 1 and the latter part resembled outbreak 3. We
      validated our use of MLVA by comparing it to WGS. Isolates with the identical
      MLVA genotype had significantly fewer mean pairwise SNV differences than those
      isolates with different MLVA genotypes (mean: 4.8 vs. 7.7, p < 0.0001).
      Furthermore, consistent with WGS results, the number of pairwise differences in
      the five MLVA loci for isolates within the same household was significantly lower
      than isolates from different households (mean: 1.6 vs. 3.0, p < 0.0001).
      CONCLUSION: These results suggest that transmission patterns for cholera are a
      combination of person-to-person and water-to-person cholera transmission with the
      proportions of the two modes varying within and between outbreaks.

PMID- 29178824
TI  - Transcriptome analysis of avian reovirus-mediated changes in gene expression of
      normal chicken fibroblast DF-1 cells.
AB  - BACKGROUND: Avian reovirus (ARV) is an important poultry pathogen that can cause
      immunosuppression. In this study, RNA-Seq technology was applied to investigate
      the transcriptome-wide changes of DF-1 cells upon ARV infection at the middle
      stage. RESULTS: Total RNA of ARV-infected or mock-infected samples at 10 and 18 h
      post infection (hpi) was extracted to build RNA-Seq datasets. Analysis of the
      sequencing data revealed that the expressions of numerous genes were altered, and
      a panel of differentially expressed genes were confirmed with RT-qPCR. At 10 hpi,
      104 genes were down-regulated and 64 were up-regulated, while the expressions of
      47 genes were increased and only one was down-regulated, which may play a role in
      retinoic acid biosynthesis, at 18 hpi in the ARV-infected cells. The similar
      profiles of up-regulated genes between the two groups of infected cells suggest
      that ARV infection activated a prolonged antiviral response of host cells.
      Alternative splicing analysis found no significantly changed events altered by
      ARV infection. CONCLUSIONS: Overall, the differential expression profile
      presented in this study can be used to expand our understanding of the
      comprehensive interactions between ARV and the host cells, and may be helpful for
      us to reveal the pathogenic mechanism on the molecular level.

PMID- 29178825
TI  - Phylogenetic relationships of cone snails endemic to Cabo Verde based on
      mitochondrial genomes.
AB  - BACKGROUND: Due to their great species and ecological diversity as well as their
      capacity to produce hundreds of different toxins, cone snails are of interest to
      evolutionary biologists, pharmacologists and amateur naturalists alike. Taxonomic
      identification of cone snails still relies mostly on the shape, color, and
      banding patterns of the shell. However, these phenotypic traits are prone to
      homoplasy. Therefore, the consistent use of genetic data for species delimitation
      and phylogenetic inference in this apparently hyperdiverse group is largely
      wanting. Here, we reconstruct the phylogeny of the cones endemic to Cabo Verde
      archipelago, a well-known radiation of the group, using mitochondrial (mt)
      genomes. RESULTS: The reconstructed phylogeny grouped the analyzed species into
      two main clades, one including Kalloconus from West Africa sister to Trovaoconus
      from Cabo Verde and the other with a paraphyletic Lautoconus due to the sister
      group relationship of Africonus from Cabo Verde and Lautoconus ventricosus from
      Mediterranean Sea and neighboring Atlantic Ocean to the exclusion of Lautoconus
      endemic to Senegal (plus Lautoconus guanche from Mauritania, Morocco, and Canary
      Islands). Within Trovaoconus, up to three main lineages could be distinguished.
      The clade of Africonus included four main lineages (named I to IV), each further
      subdivided into two monophyletic groups. The reconstructed phylogeny allowed
      inferring the evolution of the radula in the studied lineages as well as
      biogeographic patterns. The number of cone species endemic to Cabo Verde was
      revised under the light of sequence divergence data and the inferred phylogenetic
      relationships. CONCLUSIONS: The sequence divergence between continental members
      of the genus Kalloconus and island endemics ascribed to the genus Trovaoconus is
      low, prompting for synonymization of the latter. The genus Lautoconus is
      paraphyletic. Lautoconus ventricosus is the closest living sister group of genus
      Africonus. Diversification of Africonus was in allopatry due to the direct
      development nature of their larvae and mainly triggered by eustatic sea level
      changes during the Miocene-Pliocene. Our study confirms the diversity of cone
      endemic to Cabo Verde but significantly reduces the number of valid species.
      Applying a sequence divergence threshold, the number of valid species within the
      sampled Africonus is reduced to half.

PMID- 29178826
TI  - Discovering the potential of S. clavuligerus for bioactive compound production:
      cross-talk between the chromosome and the pSCL4 megaplasmid.

PMID- 29178827
TI  - Genome-wide segregation of single nucleotide and structural variants into single
      cancer cells.
AB  - BACKGROUND: Single-cell genome sequencing provides high-resolution details of the
      clonal genomic modifications that occur during cancer initiation, progression,
      and ongoing evolution as patients undergo treatment. One limitation of current
      single-cell sequencing strategies is a suboptimal capacity to detect all classes
      of single-nucleotide and structural variants in the same cells. RESULTS: Here we
      present a new approach for determining comprehensive variant profiles of single
      cells using a microfluidic amplicon-based strategy to detect structural variant
      breakpoint sequences instead of using relative read depth to infer copy number
      changes. This method can reconstruct the clonal architecture and mutational
      history of a malignancy using all classes and sizes of somatic variants,
      providing more complete details of the temporal changes in mutational classes and
      processes that led to the development of a malignant neoplasm. Using this
      approach, we interrogated cells from a patient with leukemia, determining that
      processes producing structural variation preceded single nucleotide changes in
      the development of that malignancy. CONCLUSIONS: All classes and sizes of genomic
      variants can be efficiently detected in single cancer cells using our new method,
      enabling the ordering of distinct classes of mutations during tumor evolution.

PMID- 29178828
TI  - CrusTF: a comprehensive resource of transcriptomes for evolutionary and
      functional studies of crustacean transcription factors.
AB  - BACKGROUND: Crustacea, the second largest subphylum of Arthropoda, includes
      species of major ecological and economic importance, such as crabs, lobsters,
      crayfishes, shrimps, and barnacles. With the rapid development of crustacean
      aquaculture and biodiversity loss, understanding the gene regulatory mechanisms
      of growth, reproduction, and development of crustaceans is crucial to both
      aquaculture development and biodiversity conservation of this group of organisms.
      In these biological processes, transcription factors (TFs) play a vital role in
      regulating gene expression. However, crustacean transcription factors are still
      largely unknown, because the lack of complete genome sequences of most crustacean
      species hampers the studies on their transcriptional regulation on a system-wide
      scale. Thus, the current TF databases derived from genome sequences contain TF
      information for only a few crustacean species and are insufficient to elucidate
      the transcriptional diversity of such a large animal group. RESULTS: Our database
      CrusTF ( http://qinlab.sls.cuhk.edu.hk/CrusTF ) provides comprehensive
      information for evolutionary and functional studies on the crustacean
      transcriptional regulatory system. CrusTF fills the knowledge gap of
      transcriptional regulation in crustaceans by exploring publicly available and
      newly sequenced transcriptomes of 170 crustacean species and identifying 131,941
      TFs within 63 TF families. CrusTF features three categories of information:
      sequence, function, and evolution of crustacean TFs. The database enables
      searching, browsing and downloading of crustacean TF sequences. CrusTF infers DNA
      binding motifs of crustacean TFs, thus facilitating the users to predict
      potential downstream TF targets. The database also presents evolutionary analyses
      of crustacean TFs, which improve our understanding of the evolution of
      transcriptional regulatory systems in crustaceans. CONCLUSIONS: Given the
      importance of TF information in evolutionary and functional studies on
      transcriptional regulatory systems of crustaceans, this database will constitute
      a key resource for the research community of crustacean biology and evolutionary
      biology. Moreover, CrusTF serves as a model for the construction of TF database
      derived from transcriptome data. A similar approach could be applied to other
      groups of organisms, for which transcriptomes are more readily available than
      genomes.

PMID- 29178829
TI  - ENCoRE: an efficient software for CRISPR screens identifies new players in
      extrinsic apoptosis.
AB  - BACKGROUND: As CRISPR/Cas9 mediated screens with pooled guide libraries in
      somatic cells become increasingly established, an unmet need for rapid and
      accurate companion informatics tools has emerged. We have developed a lightweight
      and efficient software to easily manipulate large raw next generation sequencing
      datasets derived from such screens into informative relational context with
      graphical support. The advantages of the software entitled ENCoRE (Easy NGS-to
      Gene CRISPR REsults) include a simple graphical workflow, platform independence,
      local and fast multithreaded processing, data pre-processing and gene mapping
      with custom library import. RESULTS: We demonstrate the capabilities of ENCoRE to
      interrogate results from a pooled CRISPR cellular viability screen following
      Tumor Necrosis Factor-alpha challenge. The results not only identified
      stereotypical players in extrinsic apoptotic signaling but two as yet
      uncharacterized members of the extrinsic apoptotic cascade, Smg7 and Ces2a. We
      further validated and characterized cell lines containing mutations in these
      genes against a panel of cell death stimuli and involvement in p53 signaling.
      CONCLUSIONS: In summary, this software enables bench scientists with sensitive
      data or without access to informatic cores to rapidly interpret results from
      large scale experiments resulting from pooled CRISPR/Cas9 library screens.

PMID- 29178830
TI  - Mosaic autosomal aneuploidies are detectable from single-cell RNAseq data.
AB  - BACKGROUND: Aneuploidies are copy number variants that affect entire chromosomes.
      They are seen commonly in cancer, embryonic stem cells, human embryos, and in
      various trisomic diseases. Aneuploidies frequently affect only a subset of cells
      in a sample; this is known as "mosaic" aneuploidy. A cell that harbours an
      aneuploidy exhibits disrupted gene expression patterns which can alter its
      behaviour. However, detection of aneuploidies using conventional single-cell DNA
      sequencing protocols is slow and expensive. METHODS: We have developed a method
      that uses chromosome-wide expression imbalances to identify aneuploidies from
      single-cell RNA-seq data. The method provides quantitative aneuploidy calls, and
      is integrated into an R software package available on GitHub and as an Additional
      file of this manuscript. RESULTS: We validate our approach using data with known
      copy number, identifying the vast majority of aneuploidies with a low rate of
      false discovery. We show further support for the method's efficacy by exploiting
      allele-specific gene expression levels, and differential expression analyses.
      CONCLUSIONS: The method is quick and easy to apply, straightforward to interpret,
      and represents a substantial cost saving compared to single-cell genome
      sequencing techniques. However, the method is less well suited to data where gene
      expression is highly variable. The results obtained from the method can be used
      to investigate the consequences of aneuploidy itself, or to exclude aneuploidy
      affected expression values from conventional scRNA-seq data analysis.

PMID- 29178831
TI  - Software for rapid time dependent ChIP-sequencing analysis (TDCA).
AB  - BACKGROUND: Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq)
      and associated methods are widely used to define the genome wide distribution of
      chromatin associated proteins, post-translational epigenetic marks, and
      modifications found on DNA bases. An area of emerging interest is to study time
      dependent changes in the distribution of such proteins and marks by using serial
      ChIP-seq experiments performed in a time resolved manner. Despite such time
      resolved studies becoming increasingly common, software to facilitate analysis of
      such data in a robust automated manner is limited. RESULTS: We have designed
      software called Time-Dependent ChIP-Sequencing Analyser (TDCA), which is the
      first program to automate analysis of time-dependent ChIP-seq data by fitting to
      sigmoidal curves. We provide users with guidance for experimental design of TDCA
      for modeling of time course (TC) ChIP-seq data using two simulated data sets.
      Furthermore, we demonstrate that this fitting strategy is widely applicable by
      showing that automated analysis of three previously published TC data sets
      accurately recapitulates key findings reported in these studies. Using each of
      these data sets, we highlight how biologically relevant findings can be readily
      obtained by exploiting TDCA to yield intuitive parameters that describe behavior
      at either a single locus or sets of loci. TDCA enables customizable analysis of
      user input aligned DNA sequencing data, coupled with graphical outputs in the
      form of publication-ready figures that describe behavior at either individual
      loci or sets of loci sharing common traits defined by the user. TDCA accepts
      sequencing data as standard binary alignment map (BAM) files and loci of interest
      in browser extensible data (BED) file format. CONCLUSIONS: TDCA accurately models
      the number of sequencing reads, or coverage, at loci from TC ChIP-seq studies or
      conceptually related TC sequencing experiments. TC experiments are reduced to
      intuitive parametric values that facilitate biologically relevant data analysis,
      and the uncovering of variations in the time-dependent behavior of chromatin.
      TDCA automates the analysis of TC ChIP-seq experiments, permitting researchers to
      easily obtain raw and modeled data for specific loci or groups of loci with
      similar behavior while also enhancing consistency of data analysis of TC data
      within the genomics field.

PMID- 29178832
TI  - Is the information of systematic reviews published in nursing journals up-to
      date? a cross-sectional study.
AB  - BACKGROUND: An up-to-date systematic review is important for researchers to
      decide whether to embark on new research or continue supporting ongoing studies.
      The aim of this study is to examine the time taken between the last search,
      submission, acceptance and publication dates of systematic reviews published in
      nursing journals. METHODS: Nursing journals indexed in Journal Citation Reports
      were first identified. Thereafter, systematic reviews published in these journals
      in 2014 were extracted from three databases. The quality of the systematic
      reviews were evaluated by the AMSTAR. The last search, submission, acceptance,
      online publication, full publication dates and other characteristics of the
      systematic reviews were recorded. The time taken between the five dates was then
      computed. Descriptive statistics were used to summarize the time differences; non
      parametric statistics were used to examine the association between the time taken
      from the last search and full publication alongside other potential factors,
      including the funding support, submission during holiday periods, number of
      records retrieved from database, inclusion of meta-analysis, and quality of the
      review. RESULTS: A total of 107 nursing journals were included in this study,
      from which 1070 articles were identified through the database search. After
      screening for eligibility, 202 systematic reviews were included in the analysis.
      The quality of these reviews was low with the median score of 3 out of 11. A
      total of 172 (85.1%), 72 (35.6%), 153 (75.7%) and 149 (73.8%) systematic reviews
      provided their last search, submission, acceptance and online published dates
      respectively. The median numbers of days taken from the last search to acceptance
      and to full publication were, respectively, 393 (IQR: 212-609) and 669 (427-915)
      whereas that from submission to full publication was 365 (243-486). Moreover, the
      median number of days from the last search to submission and from submission to
      online publication were 167.5 (53.5-427) and 153 (92-212), respectively. No
      significant association were revealed between the time lag and those potential
      factors. CONCLUSION: The median time from the last search to acceptance for
      systematic reviews published in nursing journals was 393 days. Readers for
      systematic reviews are advised to check the time taken from the last search date
      of the reviews in order to ensure that up-to-date evidence is consulted for
      effective clinical decision-making.

PMID- 29178833
TI  - Genome-wide association studies of fertility and calving traits in Brown Swiss
      cattle using imputed whole-genome sequences.
AB  - BACKGROUND: The detection of quantitative trait loci has accelerated with recent
      developments in genomics. The introduction of genomic selection in combination
      with sequencing efforts has made a large amount of genotypic data available.
      Functional traits such as fertility and calving traits have been included in
      routine genomic estimation of breeding values making large quantities of
      phenotypic data available for these traits. This data was used to investigate the
      genetics underlying fertility and calving traits and to identify potentially
      causative genomic regions and variants. We performed genome-wide association
      studies for 13 functional traits related to female fertility as well as for
      direct and maternal calving ease based on imputed whole-genome sequences.
      Deregressed breeding values from ~1000-5000 bulls per trait were used to test for
      associations with approximately 10 million imputed sequence SNPs. RESULTS: We
      identified a QTL on BTA17 associated with non-return rate at 56 days and with
      interval from first to last insemination. We found two significantly associated
      non-synonymous SNPs within this QTL region. Two more QTL for fertility traits
      were identified on BTA25 and 29. A single QTL was identified for maternal calving
      traits on BTA13 whereas three QTL on BTA19, 21 and 25 were identified for direct
      calving traits. The QTL on BTA19 co-localizes with the reported BH2 haplotype.
      The QTL on BTA25 is concordant for fertility and calving traits and co-localizes
      with a QTL previously reported to influence stature and related traits in Brown
      Swiss dairy cattle. CONCLUSION: The detection of QTL and their causative variants
      remains challenging. Combining comprehensive phenotypic data with imputed whole
      genome sequences seems promising. We present a QTL on BTA17 for female fertility
      in dairy cattle with two significantly associated non-synonymous SNPs, along with
      five additional QTL for fertility traits and calving traits. For all of these we
      fine mapped the regions and suggest candidate genes and candidate variants.

PMID- 29178834
TI  - Association of variation in the sugarcane transcriptome with sugar content.
AB  - BACKGROUND: Sugarcane is a major crop of the tropics cultivated mainly for its
      high sucrose content. The crop is genetically less explored due to its complex
      polyploid genome. Sucrose synthesis and accumulation are complex processes
      influenced by physiological, biochemical and genetic factors, and the growth
      environment. The recent focus on the crop for fibre and biofuel has led to a
      renewed interest on understanding the molecular basis of sucrose and biomass
      traits. This transcriptome study aimed to identify genes that are associated with
      and differentially regulated during sucrose synthesis and accumulation in the
      mature stage of sugarcane. Patterns of gene expression in high and low sugar
      genotypes as well as mature and immature culm tissues were studied using RNA-Seq
      of culm transcriptomes. RESULTS: In this study, 28 RNA-Seq libraries from 14
      genotypes of sugarcane differing in their sucrose content were used for studying
      the transcriptional basis of sucrose accumulation. Differential gene expression
      studies were performed using SoGI (Saccharum officinarum Gene Index, 3.0), SAS
      (sugarcane assembled sequences) of sugarcane EST database (SUCEST) and SUGIT, a
      sugarcane Iso-Seq transcriptome database. In total, about 34,476 genes were found
      to be differentially expressed between high and low sugar genotypes with the SoGI
      database, 20,487 genes with the SAS database and 18,543 genes with the SUGIT
      database at FDR < 0.01, using the Baggerley's test. Further, differential gene
      expression analyses were conducted between immature (top) and mature (bottom)
      tissues of the culm. The DEGs were functionally annotated using GO classification
      and the genes consistently associated with sucrose accumulation were identified.
      CONCLUSIONS: The large number of DEGs may be due to the large number of genes
      that influence sucrose content or are regulated by sucrose content. These results
      indicate that apart from being a primary metabolite and storage and transport
      sugar, sucrose may serve as a signalling molecule that regulates many aspects of
      growth and development in sugarcane. Further studies are needed to confirm if
      sucrose regulates the expression of the identified DEGs or vice versa. The DEGs
      identified in this study may lead to identification of genes/pathways regulating
      sucrose accumulation and/or regulated by sucrose levels in sugarcane. We propose
      identifying the master regulators of sucrose if any in the future.

PMID- 29178835
TI  - Phylogenetics of subtribe Orchidinae s.l. (Orchidaceae; Orchidoideae) based on
      seven markers (plastid matK, psaB, rbcL, trnL-F, trnH-psba, and nuclear nrITS,
      Xdh): implications for generic delimitation.
AB  - BACKGROUND: Subtribe Orchidinae (Orchidaceae, Orchidoideae) are a nearly
      cosmopolitan taxon of terrestrial orchids, comprising about 1800 species in 47 to
      60 genera. Although much progress has been made in recent years of phylogenetics
      of Orchidinae, considerable problems remain to be addressed. Based on molecular
      phylogenetics, we attempt to illustrate the phylogenetic relationships and
      discuss generic delimitation within Orchidinae. Seven DNA markers (five plastid
      and two nuclear), a broad sampling of Orchidinae (400 species in 52 genera) and
      three methods of phylogenetic analysis (maximum likelihood, maximum parsimony and
      Bayesian inference) were used. RESULTS: Orchidinae s.l. are monophyletic.
      Satyrium is sister to the rest of Orchidinae s.l. Brachycorythis and Schizochilus
      are successive sister to Asian-European Orchidinae s.s. Sirindhornia and
      Shizhenia are successive sister to clade formed by Tsaiorchis-Hemipilia
      Ponerorchis alliance. Stenoglottis is sister to the Habenaria-Herminium
      Peristylus alliance. Habenaria, currently the largest genus in Orchidinae, is
      polyphyletic and split into two distant clades: one Asian-Australian and the
      other African-American-Asian. Diplomeris is sister to Herminium s.l. plus Asian
      Australian Habenaria. CONCLUSIONS: We propose to recognize five genera in the
      Ponerorchis alliance: Hemipilia, Ponerorchis s.l., Sirindhornia, Shizhenia and
      Tsaiorchis. Splitting Habenaria into two genera based on morphological characters
      and geographical distribution may be the least disruptive approach, and it is
      reasonable to keep Satyrium in Orchidinae.

PMID- 29178836
TI  - Chromosome level assembly and secondary metabolite potential of the parasitic
      fungus Cordyceps militaris.
AB  - BACKGROUND: Cordyceps militaris is an insect pathogenic fungus that is prized for
      its use in traditional medicine. This and other entomopathogenic fungi are
      understudied sources for the discovery of new bioactive molecules. In this study,
      PacBio SMRT long read sequencing technology was used to sequence the genome of C.
      militaris with a focus on the genetic potential for secondary metabolite
      production in the genome assembly of this fungus. RESULTS: This is first
      chromosome level assembly of a species in the Cordyceps genera. In this seven
      chromosome assembly of 33.6 Mba there were 9371 genes identified. Cordyceps
      militaris was determined to have the MAT 1-1-1 and MAT 1-1-2 mating type genes.
      Secondary metabolite analysis revealed the potential for at least 36 distinct
      metabolites from a variety of classes. Three of these gene clusters had homology
      with clusters producing desmethylbassianin, equisetin and emericellamide that had
      been studied in other fungi. CONCLUSION: Our assembly and analysis has revealed
      that C. militaris has a wealth of gene clusters for secondary metabolite
      production distributed among seven chromosomes. The identification of these gene
      clusters will facilitate the future study and identification of the secondary
      metabolites produced by this entomopathogenic fungus.

PMID- 29178837
TI  - VISPA2: a scalable pipeline for high-throughput identification and annotation of
      vector integration sites.
AB  - BACKGROUND: Bioinformatics tools designed to identify lentiviral or retroviral
      vector insertion sites in the genome of host cells are used to address the safety
      and long-term efficacy of hematopoietic stem cell gene therapy applications and
      to study the clonal dynamics of hematopoietic reconstitution. The increasing
      number of gene therapy clinical trials combined with the increasing amount of
      Next Generation Sequencing data, aimed at identifying integration sites, require
      both highly accurate and efficient computational software able to correctly
      process "big data" in a reasonable computational time. RESULTS: Here we present
      VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest
      optimized computational pipeline for integration site identification and analysis
      with the following features: (1) the sequence analysis for the integration site
      processing is fully compliant with paired-end reads and includes a sequence
      quality filter before and after the alignment on the target genome; (2) an
      heuristic algorithm to reduce false positive integration sites at nucleotide
      level to reduce the impact of Polymerase Chain Reaction or trimming/alignment
      artifacts; (3) a classification and annotation module for integration sites; (4)
      a user friendly web interface as researcher front-end to perform integration site
      analyses without computational skills; (5) the time speedup of all steps through
      parallelization (Hadoop free). CONCLUSIONS: We tested VISPA2 performances using
      simulated and real datasets of lentiviral vector integration sites, previously
      obtained from patients enrolled in a hematopoietic stem cell gene therapy
      clinical trial and compared the results with other preexisting tools for
      integration site analysis. On the computational side, VISPA2 showed a > 6-fold
      speedup and improved precision and recall metrics (1 and 0.97 respectively)
      compared to previously developed computational pipelines. These performances
      indicate that VISPA2 is a fast, reliable and user-friendly tool for integration
      site analysis, which allows gene therapy integration data to be handled in a cost
      and time effective fashion. Moreover, the web access of VISPA2 (
      http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to
      researches of a complex analytical tool. We released the source code of VISPA2 in
      a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).

PMID- 29178838
TI  - Hepatitis C virus eradication improves immediate and delayed episodic memory in
      patients treated with interferon and ribavirin.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with
      impairment of cognitive function and mood disorders. Our aim was to evaluate the
      impact of sustained virological response (SVR) on cognitive function and mood
      disorders. METHOD: A prospective exploratory one arm study was conducted. Adult
      clinically compensated HVC patients were consecutively recruited before treatment
      with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype.
      Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI
      instruments were performed at baseline, right after half of the expected
      treatment has been reached and 6 months after the end of antiviral treatment.
      Exclusion criteria were the use of illicit psychotropic substances, mental
      confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia,
      untreated hypothyroidism, Addison syndrome and major depression before treatment.
      RESULTS: Thirty six patients were enrolled and 21 completed HCV treatment (n = 16
      with SVR and n = 5 without). Regardless of the viral clearance at the end of
      treatment, there was a significant improvement in the immediate verbal episodic
      memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective
      attention (p < 0.001) and phonemic fluency (p = 0.043). Patients with SVR
      displayed significant improvement in immediate (p = 0.045) and delayed verbal
      episodic memory (p = 0.040) compared to baseline. The baseline frequency of
      depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6
      months after the end of treatment, without significant difference between
      patients with and without SVR. Depressive symptoms were observed in 19.1% before
      treatment, 62% during (p = 0.016) and 28.6% 6 months after the end of treatment
      (p = 0.719). CONCLUSIONS: Eradication of HCV infection improved cognitive
      performance but did not affect the frequency of depressive symptoms at least in
      the short range.

PMID- 29178839
TI  - Effects of IFN-gamma coding plasmid supplementation in the immune response and
      protection elicited by Trypanosoma cruzi attenuated parasites.
AB  - BACKGROUND: Previous studies showed that a naturally attenuated strain from
      Trypanosoma cruzi triggers an immune response mainly related to a Th2-type
      profile. Albeit this, a strong protection against virulent challenge was obtained
      after priming mice with this attenuated strain. However, this protection is not
      enough to completely clear parasites from the host. In T. cruzi infection, early
      Interferon-gamma (IFN-gamma) is critical to lead type 1 responses able to control
      intracellular parasites. Therefore we evaluated whether the co-administration of
      a plasmid encoding murine IFN-gamma could modify the immune response induced by
      infection with attenuated parasites and improve protection against further
      infections. METHODS: C57BL/6J mice were infected intraperitoneally with three
      doses of live attenuated parasites in combination with plasmid pVXVR-mIFN-gamma.
      Before each infection dose, sera samples were collected for parasite specific
      antibodies determination and cytokine quantification. To evaluate the recall
      response to T. cruzi, mice were challenged with virulent parasites 30 days after
      the last dose and parasite load in peripheral blood and heart was evaluated.
      RESULTS: As determined by ELISA, significantly increase in T. cruzi specific
      antibodies response was detected in the group in which pVXVR-mIFN-gamma was
      incorporated, with a higher predominance of IgG2a subtype in comparison to the
      group of mice only inoculated with attenuated parasites. At our limit of
      detection, serum levels of IFN-gamma were not detected, however a slight decrease
      in IL-10 concentrations was observed in groups in which pVXVR-mIFN-gamma was
      supplemented. To analyze if the administration of pVXVR-mIFN-gamma has any
      beneficial effect in protection against subsequent infections, all experimental
      groups were submitted to a lethal challenge with virulent bloodstream
      trypomastigotes. Similar levels of challenge parasites were detected in
      peripheral blood and heart of mice primed with attenuated parasites alone or
      combined with plasmid DNA. Expansion of IgG antibodies was not significant in
      TCC+ pVXVR-mIFN-gamma; however, the overall tendency to sustain a Th2 profile was
      maintained. CONCLUSIONS: Overall, these results suggest that administration of
      plasmid pVXVR-mIFN-gamma could have beneficial effects on host specific antibody
      production in response to T. cruzi attenuated infection; however, this outcome is
      not reflected in an improved protection against further virulent infections.

PMID- 29178840
TI  - Prevalence of oncogenic human papillomavirus genotypes in patients diagnosed with
      anogenital malignancies in Botswana.
AB  - BACKGROUND: Human papillomavirus (HPV) associated malignancies are the leading
      cause of cancer death in Botswana. We sought to determine causative HPV types in
      patients with anogenital malignancies in Botswana to inform vaccine strategy.
      METHODS: We used formalin-fixed and paraffin-embedded (FFPE) tissue blocks from
      patients diagnosed with anal, penile and vulvar squamous cell carcinomas between
      the years, 2014 and 2016. Presence of HPV 16, 18, or other high-risk (HR) types
      was detected using Abbott m2000 real-time PCR platform. Tissues with other high
      risk types were subsequently analysed using a multiplex qPCR assay that includes
      15 validated fluorophore probes. RESULTS: A total of 126 tissue specimens,
      comprising of 21 anal (9 males, 12 females), 31 penile and 74 vulvar were
      studied. Ninety-three (73.8%) patients had their HIV status documented in the
      records while the rest did not. Eighty-three (83) out of 93 were HIV positive, a
      prevalence of 89.4% (95% CI: 81-94). HPV was detected in 68/126 (54%) tissues, of
      which 69% (95% CI: 54-79) had HPV 16 only, 28% (95% CI: 19-40) had other hr.-HPV
      types and 2.9% (95% CI, 3.5-10.1) were co-infected with HPV 16 and other hr.
      types. Other high-risk types detected included HPV 26, 31, 33, 35, 39, 45, 51,
      52, 66 and 68. HPV 18 was not detected. Multiple-type HPV infection was detected
      in 44 of 47 (93.6%) HIV positive participants co-infected with HPV. In HIV
      negative individuals, only HPV 16 was detected. CONCLUSION: In our study,
      anogenital carcinomas were associated with HPV 16 and other hr.-HPV types besides
      HPV 16 and 18. HIV co-infected patients had multiple hr.-HPV types detected
      whereas in HIV-negative patients only HPV 16 was detected. Our study suggests
      that multivalent vaccines may be more suitable in this setting, especially for
      HIV-infected individuals.

PMID- 29178841
TI  - Multiresistant ST59-SCCmec IV-t437 clone with strong biofilm-forming capacity was
      identified predominantly in MRSA isolated from Chinese children.
AB  - BACKGROUND: This study aimed to investigate the clinical and molecular
      epidemiology and biofilm formation of Staphylococcus aureus (SA) isolated from
      pediatricians in China. METHODS: SA strains were isolated from Beijing Children's
      hospital from February 2016 to January 2017. Isolates were typed by multilocus
      sequence typing (MLST), spa and SCCmec typing (for Methicillin-resistant SA
      [MRSA] only). Antimicrobial susceptibility testing was performed by agar dilution
      method except sulphamethoxazole/trimethoprim (E-test method). Biofilm formation
      and biofilm associated genes were detected. RESULTS: Totally 104 children (41
      females and 63 males; median age, 5.2 months) were enrolled in this study, in
      which 60 patients suffered from MRSA infection. Among the 104 cases, 54.8% were
      categorized as community associated SA (CA-SA) infections. The children under 3
      years were more likely to occur CA-SA infections compared with older ones (P =
      0.0131). ST59-SCCmec IV-t437 (61.7%) was the most prevalent genotype of MRSA, and
      ST22-t309 (18.2%), ST5-t002 (9.1%), ST6-t701 (9.1%), ST188-t189 (9.1%) were the
      top four genotypes of methicillin-sensitive SA (MSSA). All the present isolates
      were susceptible to linezolid, vancomycin, trimethoprim-sulfamethoxazole,
      mupirocin, tigecyclin, fusidic acid. No erythromycin-susceptible isolate was
      determined, and only a few isolates (3.8%) were identified as susceptible to
      penicillin. Multi-drug resistant isolates were reponsible for 83.8% of the ST59
      SCCmec IV-t437 isolates. The isolates with strong biofilm formation were found in
      85% of MRSA and 53.2% of MSSA, and in 88.7% of ST59-SCCmec IV-t437 isolates.
      Biofilm formation ability varied not only between MRSA and MSSA (P = 0.0053), but
      also greatly among different genotypes (P < 0.0001). The prevalence of the
      biofilm associated genes among ST59-SCCmec IV-t437 clone was: icaA (100.0%), icaD
      (97.3%), fnbpA (100.0%), fnbpB (0), clfA (100%), clfB (100%), cna (2.7%), bbp
      (0), ebpS (88.5%), sdrC (78.4%), sdrD (5.4%), and sdrE (94.5%). CONCLUSIONS:
      These results indicated strong homology of the MRSA stains isolated from Chinese
      children, which was caused by spread of multiresistant ST59-SCCmec IV-t437 clone
      with strong biofilm formation ability. The MSSA strains, in contrast, were very
      heterogeneity, half of which could produce biofilm strongly.

PMID- 29178842
TI  - A non-interventional, observational study of a fixed combination of pepsin and
      amino acid hydrochloride in patients with functional dyspepsia.
AB  - BACKGROUND: Functional dyspepsia (FD) is a gastrointestinal disorder
      characterized by recurrent and diverse symptoms and pathophysiology that remains
      unexplained following routine clinical investigation. Enzynorm(r)f is a
      pharmaceutical preparation comprising fixed amounts of pepsin of biological
      origin and organically bound acid in the form of amino acid hydrochloride. It is
      traditionally used as a mild agent to support gastric function and to stimulate
      the stomach's proteolytic activities in FD. METHODS: In a non-interventional,
      observational, post-marketing surveillance study, patients with an established
      diagnosis of FD were treated with a fixed combination of pepsin and amino acid
      hydrochloride taken as tablets three times daily for 6 weeks. The primary
      objective of this study was to assess the change in symptoms using the validated
      Gastrointestinal Symptom Score (GIS(c)). Secondary objectives included patients'
      assessment of their gastrointestinal symptoms as well as treatment safety and
      tolerability. RESULTS: A total of 97 patients (mean age 58.4 +/- 13.9 years;
      63.2% females) were included in the study, with 72 data having GIS(c) score data
      at baseline and at 6 weeks, and 34 also at 3 weeks. The overall GIS(c) sum score
      decreased by 4.1 (p < 0.0001) from 11.6 (+/-4.8) at baseline to 7.4 (+/- 4.6)
      reflecting an improvement of clinical symptomatology after 6 weeks of treatment.
      In a subgroup of 70 patients who had FD meeting the Rome III criteria a GIS(c)
      score reduction of >=50% was observed after 3 weeks treatment in 24% and in 30.8%
      after 6 weeks. Adverse events were mostly gastrointestinal in nature and
      consistent with the underlying disease; no unexpected adverse reactions were
      reported. Twenty-seven patients discontinued the study, mostly because of
      gastrointestinal symptoms. CONCLUSION: The results of this study support the
      efficacy of a fixed combination of pepsin and amino acid hydrochloride for the
      treatment of patients with FD and also suggest good to moderate treatment
      tolerability. These findings should be further explored in a randomised, placebo
      controlled clinical trial. CLINICAL TRIAL REGISTRATION: This study has been
      retrospectively registered in the ClinicalTrials.gov registry, trial identifier
      NCT03076411 .

PMID- 29178843
TI  - A qualitative evidence synthesis to explore healthcare professionals' experience
      of prescribing opioids to adults with chronic non-malignant pain.
AB  - BACKGROUND: Despite recent guidelines suggesting that patients with chronic non
      malignant pain might not benefit, there has been a significant rise in opioid
      prescription for chronic non-malignant pain. This topic is important because an
      increasing number of HCPs are prescribing opioids despite very limited evidence
      for long-term opioid therapy for chronic non-malignant pain outside of end-of
      life care. To better understand the challenges of providing effective treatment,
      we conducted the first qualitative evidence synthesis to explore healthcare
      professionals' experience of treating people with chronic non-malignant pain. We
      report findings that explore healthcare professionals' experience of prescribing
      opioids to this group of patients. METHODS: We searched five electronic
      bibliographic databases (Medline, Embase, CINAHL, PsychINFO, AMED) from inception
      to November 2015 and screened titles, abstracts and full texts of potential
      studies. We included studies in English that explored healthcare professionals'
      experience of treating adults with chronic non-malignant pain. Two reviewers
      quality appraised each paper. We used the methods of meta-ethnography developed
      and refined for large reviews, and the GRADE-CERQual framework to rate confidence
      in review findings. RESULTS: We screened 954 abstracts and 184 full texts, and
      included 77 studies in the full review. 17 of these 77 studies included concepts
      that explored the experience of prescribing opioids. We abstracted these concepts
      into 6 overarching themes: (1) Should I, shouldn't I? (2) Pain is Pain; (3)
      Walking a fine line; (4) Social guardianship; (5) Moral boundary work; (6)
      Regulations and guidelines. We used the GRADE-CERQual framework to evaluate
      confidence in findings. A new overarching concept of 'ambiguity' explains the
      balancing required around the factors taken into account when prescribing
      opioids. Managing this ambiguity is challenging and these findings can inform
      healthcare professionals dealing with these decisions. CONCLUSIONS: This
      conceptual model demonstrates the complexity of making a decision to prescribe
      opioids to someone with chronic non-malignant pain. Although opioid prescription
      is underpinned by the therapeutic aim of alleviating pain, this aim may be
      misplaced. This has implications for education in light of the new regulations
      for opioid prescription. Findings also demonstrate that the decision is
      influenced by intra- and interpersonal factors and broader external concerns.

PMID- 29178844
TI  - BoolFilter: an R package for estimation and identification of partially-observed
      Boolean dynamical systems.
AB  - BACKGROUND: Gene regulatory networks govern the function of key cellular
      processes, such as control of the cell cycle, response to stress, DNA repair
      mechanisms, and more. Boolean networks have been used successfully in modeling
      gene regulatory networks. In the Boolean network model, the transcriptional state
      of each gene is represented by 0 (inactive) or 1 (active), and the relationship
      among genes is represented by logical gates updated at discrete time points.
      However, the Boolean gene states are never observed directly, but only indirectly
      and incompletely through noisy measurements based on expression technologies such
      as cDNA microarrays, RNA-Seq, and cell imaging-based assays. The Partially
      Observed Boolean Dynamical System (POBDS) signal model is distinct from other
      deterministic and stochastic Boolean network models in removing the requirement
      of a directly observable Boolean state vector and allowing uncertainty in the
      measurement process, addressing the scenario encountered in practice in
      transcriptomic analysis. RESULTS: BoolFilter is an R package that implements the
      POBDS model and associated algorithms for state and parameter estimation. It
      allows the user to estimate the Boolean states, network topology, and measurement
      parameters from time series of transcriptomic data using exact and approximated
      (particle) filters, as well as simulate the transcriptomic data for a given
      Boolean network model. Some of its infrastructure, such as the network interface,
      is the same as in the previously published R package for Boolean Networks
      BoolNet, which enhances compatibility and user accessibility to the new package.
      CONCLUSIONS: We introduce the R package BoolFilter for Partially-Observed Boolean
      Dynamical Systems (POBDS). The BoolFilter package provides a useful toolbox for
      the bioinformatics community, with state-of-the-art algorithms for simulation of
      time series transcriptomic data as well as the inverse process of system
      identification from data obtained with various expression technologies such as
      cDNA microarrays, RNA-Seq, and cell imaging-based assays.

PMID- 29178845
TI  - Classification of a new phytoplasmas subgroup 16SrII-W associated with Crotalaria
      witches' broom diseases in Oman based on multigene sequence analysis.
AB  - BACKGROUND: Crotalaria aegyptiaca, a low shrub is commonly observed in the sandy
      soils of wadis desert and is found throughout all regions in Oman. A survey for
      phytoplasma diseases was conducted. During a survey in a wild area in the
      northern regions of Oman in 2015, typical symptoms of phytoplasma infection were
      observed on C. aegyptiaca plants. The infected plants showed an excessive
      proliferation of their shoots and small leaves. RESULTS: The presence of
      phytoplasma in the phloem tissue of symptomatic C. aegyptiaca leaf samples was
      confirmed by using Transmission Electron Microscopy (TEM). In addition the
      extracted DNA from symptomatic C. aegyptiaca leaf samples and Orosius sp.
      leafhoppers were tested by PCR using phytoplasma specific primers for the 16S
      rDNA, secA, tuf and imp, and SAP11 genes. The PCR amplifications from all samples
      yielded the expected products, but not from asymptomatic plant samples. Sequence
      similarity and phylogenetic tree analyses of four genes (16S rDNA, secA, tuf and
      imp) showed that Crotalaria witches' broom phytoplasmas from Oman is placed with
      the clade of Peanut WB (16SrII) close to Fava bean phyllody (16SrII-C), Cotton
      phyllody and phytoplasmas (16SrII-F), and Candidatus Phytoplasma aurantifolia'
      (16SrII-B). However, the Crotalaria's phytoplasma was in a separate sub-clade
      from all the other phytoplasmas belonging to Peanut WB group. The combination of
      specific primers for the SAP11 gene of 16SrII-A, -B, and -D subgroup pytoplasmas
      were tested against Crotalaria witches' broom phytoplasmas and no PCR product was
      amplified, which suggests that the SAP11 of Crotalaria phytoplasma is different
      from the SAP11 of the other phytoplasmas. CONCLUSION: We propose to assign the
      Crotalaria witches' broom from Oman in a new lineage 16SrII-W subgroup depending
      on the sequences analysis of 16S rRNA, secA, imp, tuf, and SAP11 genes. To our
      knowledge, this is the first report of phytoplasmas of the 16SrII group infecting
      C. aegyptiaca worldwide.

PMID- 29178846
TI  - An optimized protocol for the preparation of oxygen-evolving thylakoid membranes
      from Cyclotella meneghiniana provides a tool for the investigation of diatom
      plastidic electron transport.
AB  - BACKGROUND: The preparation of functional thylakoid membranes from diatoms with a
      silica cell wall is still a largely unsolved challenge. Therefore, an optimized
      protocol for the isolation of oxygen evolving thylakoid membranes of the centric
      diatom Cyclotella meneghiniana has been developed. The buffer used for the
      disruption of the cells was supplemented with polyethylene glycol based on its
      stabilizing effect on plastidic membranes. Disruption of the silica cell walls
      was performed in a French Pressure cell and subsequent linear sorbitol density
      gradient centrifugation was used to isolate the thylakoid membrane fraction.
      RESULTS: Spectroscopic characterization of the thylakoids by absorption and 77 K
      fluorescence spectroscopy showed that the photosynthetic pigment protein
      complexes in the isolated thylakoid membranes were intact. This was supported by
      oxygen evolution measurements which demonstrated high electron transport rates in
      the presence of the artificial electron acceptor DCQB. High photosynthetic
      activity of photosystem II was corroborated by the results of fast fluorescence
      induction measurements. In addition to PSII and linear electron transport,
      indications for a chlororespiratory electron transport were observed in the
      isolated thylakoid membranes. Photosynthetic electron transport also resulted in
      the establishment of a proton gradient as evidenced by the quenching of 9-amino
      acridine fluorescence. Because of their ability to build-up a light-driven proton
      gradient, de-epoxidation of diadinoxanthin to diatoxanthin and diatoxanthin
      dependent non-photochemical quenching of chlorophyll fluorescence could be
      observed for the first time in isolated thylakoid membranes of diatoms. However,
      the ?pH, diadinoxanthin de-epoxidation and diatoxanthin-dependent NPQ were weak
      compared to intact diatom cells or isolated thylakoids of higher plants.
      CONCLUSIONS: The present protocol resulted in thylakoids with a high electron
      transport capacity. These thylakoids can thus be used for experiments addressing
      various aspects of the photosynthetic electron transport by, e.g., employing
      artificial electron donors and acceptors which do not penetrate the diatom cell
      wall. In addition, the present isolation protocol yields diatom thylakoids with
      the potential for xanthophyll cycle and non-photochemical quenching measurements.
      However, the preparation has to be further refined before these important topics
      can be addressed systematically.

PMID- 29178848
TI  - Anti-fibrotic, anti-VEGF or radiotherapy treatments as adjuvants for pterygium
      excision: a systematic review and network meta-analysis.
AB  - BACKGROUND: Anti-fibrotic, anti-VEGF (vascular endothelial growth factor)
      medications, or radiotherapy, as adjuvant for pterygium surgical procedure, has
      been suggested for reducing recurrence, but difficulties may be experienced in
      deciding which treatment to use. The purpose of this study was to compare the
      efficacies of these different adjuvants for preventing recurrence following
      pterygium surgery. METHODS: We conducted a systematic review to identify
      randomized controlled trials of patients with primary or recurrent pterygium who
      received anti-fibrotic, anti-VEGF medication, or radiotherapy as adjuvants in
      combination with surgical procedure. The surgical procedure contained bare sclera
      technique or petrygium excision combination with tissue grafting. The primary
      outcome of this study was recurrence. Direct-comparison and Bayesian network meta
      analyses were performed to assess direct and indirect evidence of efficacy.
      RESULTS: We obtained data from 34 randomized controlled trials, representing a
      total of 2483 patients. Adjuvants included bevacizumab, 5-FU (5-fluorouracil),
      MMC (mitomycin C), and beta-RT (beta-radiotherapy). Compared with placebo, we
      found distinguishable improvement in recurrence with bevacizumab (odds ratio [OR]
      0.38, 95% confidence interval [CI] 0.18-0.80), MMC (0.12, 95% CI 0.06-0.21), and
      beta-RT (0.17, 95% CI 0.04-0.69), but not with 5-FU (0.41, 95% CI 0.12-1.39). MMC
      significantly reduced recurrence when compared to bevacizumab (0.31, 95% CI 0.13
      0.77) and 5-FU (0.28, 95% CI 0.08-0.99). The probability of having the most
      recurrences after excision was lowest for MMC, followed by bevacizumab and beta
      RT. Similar results were found in subgroup analyses, including for primary
      pterygium, and the patients receiving bare sclera technique or conjunctival
      autograft. CONCLUSIONS: Adjuvants such as MMC, bevacizumab, and beta-RT could
      effectively prevent recurrence following pterygium excision. However, their
      efficacy and acceptability require further clarification in future randomized
      controlled trials.

PMID- 29178849
TI  - Goldmann applanation tonometry error relative to true intracameral intraocular
      pressure in vitro and in vivo.
AB  - BACKGROUND: Goldmann applanation tonometry (GAT) error relative to intracameral
      intraocular pressure (IOP) has not been examined comparatively in both human
      cadaver eyes and in live human eyes. Futhermore, correlations to biomechanical
      corneal properties and positional changes have not been examined directly to
      intracameral IOP and GAT IOP. METHODS: Intracameral IOP was measured via pressure
      transducer on fifty-eight (58) eyes undergoing cataract surgery and the IOP was
      modulated manometrically on each patient alternately to 10, 20, and 40 mmHg. IOP
      was measured using a Perkins tonometer in the supine position on 58 eyes and
      upright on a subset of 8 eyes. Twenty one (21) fresh human cadaver globes were
      Intracamerally IOP adjusted and measured via pressure transducer. Intracameral
      IOP ranged between 5 and 60 mmHg. IOP was measured in the upright position with a
      Goldmann Applanation Tonometer (GAT) and supine position with a Perkins
      tonometer. Central corneal thickness (CCT) was also measured. RESULTS: The
      Goldmann-type tonometer error measured on live human eyes was 5.2 +/-1.6 mmHg
      lower than intracameral IOP in the upright position and 7.9 +/- 2.3 mmHg lower in
      the supine position (p < .05). CCT also indicated a sloped correlation to error
      (correlation coeff. = 0.18). Cadaver eye IOP measurements were 3.1+/-2.5 mmHg
      lower than intracameral IOP in the upright position and 5.4+/- 3.1 mmHg in the
      supine position (p < .05). CONCLUSION: Goldmann IOP measures significantly lower
      than true intracameral IOP by approximately 3 mmHg in vitro and 5 mmHg in vivo.
      The Goldmann IOP error is increased an additional 2.8 mmHg lower in the supine
      position. CCT appears to significantly affect the error by up to 4 mmHg over the
      sample size.

PMID- 29178850
TI  - Factors associated with the occurrence of a fall in subjects with primary open
      angle glaucoma.
AB  - BACKGROUND: The aim of the study is to investigate risk factors for future falls
      in subject with primary open angle glaucoma (POAG). METHODS: All participants
      answered the following question at their baseline ophthalmic examination: Have
      you had any falls in the last year? (Yes/No). All study participants answered the
      same question every 12 months for 3 years. The means of total deviation values in
      the whole, superior peripheral, superior central, inferior central, and inferior
      peripheral visual fields (VF) were calculated. The relationship between these
      mean VF measurements, and various clinical factors against patients' future falls
      was analyzed using multiple linear regression. RESULTS: Two-hundred ninety four
      POAG patients answered the baseline and follow-up fall questionnaires over a
      period of three years. Among 294 subjects, 69 patients experienced a fall during
      the three-year follow-up. History of falls at baseline (coefficient = 1.22),
      history of fear of falling at baseline (0.53), best corrected visual acuity in
      the worse eye (7.37), prevalence of diabetes mellitus (0.60), prevalence of
      systemic hypertension (0.53) were selected in the optimal model. CONCLUSIONS:
      Visual acuity in the worse eye, history of falls, fear of falling, diabetes
      mellitus, and systemic hypertension are risk factors for falling in subjects with
      POAG.

PMID- 29178851
TI  - Bacterial profile of ocular infections: a systematic review.
AB  - BACKGROUND: Bacteria are the major contributor of ocular infections worldwide.
      Ocular infections, if left untreated, can damage the structures of the eye with
      possible blindness and visual impairments. This work was aimed to review the
      bacterial profile of ocular infections. METHODS: Literature search was made in
      different electronic databases; the review was systematically made to get
      concrete findings. RESULTS: As far as this review, Staphylococcus aureus,
      Coagulase negative Staphylococci, Streptococcus pneumoniae and Pseudomonas
      aeruginosa are the leading isolates in ocular infections. Frequent pathogens of
      the respective clinical diagnose include Staphylococci, Streptococcus pyogenes
      and Pseudomonas aeruginosa in blepharitis; Staphylococci, Streptococus
      pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli in
      Conjunctivitis; Staphylococci, P. aeruginosa and E. coli in dacryocystitis;
      Coagulase negative Staphylococci, Pseudomonas aeruginosa and Staphylococcus
      aureus in keratitis; Streptococcus viridians, Streptococcus pneumoniae and
      Coagulase negative Staphylococci in endophthalmitis diagnoses. Endogenous
      endophthalmitis is associated with Klebsiella pneumoniae whereas Coagulase
      negative Staphylococci and Bacillus spp. are common causes of post-operative and
      post-traumatic endophthalmitis. However, the predominant pathogens may not be
      exactly same in all areas of the world, in the United States for instance,
      Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae are
      the major causes of conjunctivitis. CONCLUSION: Gram positive bacteria are the
      major contributor of bacterial ocular infections. The distribution and proportion
      of bacterial isolates among clinical diagnoses varied but without exclusive
      anatomical restriction. To mitigate the burden of bacterial ocular infections,
      physicians should regard on risk reduction and comply with etiologic approach of
      diagnosis.

PMID- 29178852
TI  - Couples HIV counselling and couple relationships in India, Georgia and the
      Dominican Republic.
AB  - BACKGROUND: Couples HIV counseling and testing is essential for combination HIV
      prevention, but its uptake remains very low. We aimed to evaluate factors
      associated with couples HIV counseling uptake in India, Georgia and the Dominican
      Republic, as part of the ANRS 12127 Prenahtest intervention trial. METHODS:
      Pregnant women >=15 years, attending their first antenatal care (ANC) session
      between March and September 2009, self-reporting a stable partner, and having
      received couple-oriented post-test HIV counseling (trial intervention) were
      included. Individuals and couple characteristics associated with the
      acceptability of couples HIV counseling were assessed using multivariable
      logistic regression for each study site. RESULTS: Among 711 women included (232,
      240 and 239 in the Dominican Republic, Georgia and India, respectively), the
      uptake of couples HIV counseling was 9.1% in the Dominican Republic, 13.8% in
      Georgia and 36.8% in India. The uptake of couples HIV counseling was associated
      with women having been accompanied by their partner to ANC, and never having used
      a condom with their partner in the Dominican Republic; with women having been
      accompanied by their partner to ANC in India; with women having a higher
      educational level than their partner and having ever discussed HIV with their
      partner in Georgia. CONCLUSION: Couple HIV counseling uptake was overall low.
      Strategies adapted to local socio-cultural contexts, aiming at improving women's
      education level, or tackling gender norms to facilitate the presence of men in
      reproductive health services, should be considered. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01494961 . Registered December 15, 2011.
      (Retrospectively registered).

PMID- 29178853
TI  - Pleural plaques in lung cancer screening by low-dose computed tomography:
      prevalence, association with lung cancer and mortality.
AB  - BACKGROUND: To report the prevalence of pleural plaques in a lung cancer
      screening trial by low-dose computed tomography (LDCT) and to test the
      association with incidence of lung cancer and mortality. METHODS: The LDCT of
      2303 screenees were retrospectively reviewed with the specific aim of describing
      the prevalence and features of pleural plaques. Self-administered questionnaire
      was used to assess asbestos exposure. Frequency of lung cancer, lung cancer
      mortality, and overall mortality were detailed according to presence of pleural
      findings. Statistical analyses included comparison of mean or median, contingency
      tables, and Cox model for calculation of hazard ratio (HR) and its 95% confidence
      interval (CI). RESULTS: Among male screenees, 31/1570 (2%) showed pleural
      abnormalities, 128/1570 (8.2%) disclosed asbestos exposure, 23/31 (74.2%)
      subjects with pleural plaques consistently denied exposure to asbestos. There was
      a trend for higher frequency of lung cancer among subjects with pleural plaques
      (9.7% vs 4.2%). Lung cancer in subjects with pleural plaques was always diagnosed
      in advanced stage. Subjects with pleural plaques showed HR 5.48 (95% CI 1.61
      18.70) for mortality from lung cancer. CONCLUSIONS: Pleural plaques are a risk
      factor for lung cancer mortality that can be detected in lung cancer screening by
      LDCT, also in subjects that are not aware of asbestos exposure. TRIAL
      REGISTRATION: NCT02837809 - Retrospectively registered July 1, 2016 - Enrolment
      of first participant September 2005.

PMID- 29178847
TI  - HIV serostatus knowledge and serostatus disclosure with the most recent anal
      intercourse partner in a European MSM sample recruited in 13 cities: results from
      the Sialon-II study.
AB  - BACKGROUND: Knowledge of HIV status can be important in reducing the risk of HIV
      exposure. In a European sample of men-who-have-sex-with-men (MSM), we aimed to
      identify factors associated with HIV serostatus disclosure to the most recent
      anal intercourse (AI) partner. We also aimed to describe the impact of HIV
      serostatus disclosure on HIV exposure risks. METHODS: During 2013 and 2014, 4901
      participants were recruited for the bio-behavioural Sialon-II study in 13
      European cities. Behavioural data were collected with a self-administered paper
      questionnaire. Biological specimens were tested for HIV antibodies. Factors
      associated with HIV serostatus disclosure with the most recent AI partner were
      examined using bivariate and multilevel multivariate logistic regression
      analysis. We also describe the role of serostatus disclosure for HIV exposure of
      the most recent AI partner. RESULTS: Thirty-five percent (n = 1450) of the study
      participants reported mutual serostatus disclosure with their most recent AI
      partner or disclosed having HIV to their partner. Most of these disclosures
      occurred between steady partners (74%, n = 1077). In addition to the type of
      partner and HIV diagnosis status, other factors positively associated with HIV
      serostatus disclosure in the multilevel multivariate logistic regression model
      were recent testing, no condom use, and outness regarding sexual orientation.
      Disclosure rates were lowest in three south-eastern European cities. Following
      condom use (51%, n = 2099), HIV serostatus disclosure (20%, n = 807) was the
      second most common prevention approach with the most recent AI partner, usually
      resulting in serosorting. A potential HIV exposure risk for the partner was
      reported by 26% (111/432) of HIV antibody positive study participants. In 18%
      (20/111) of exposure episodes, an incorrect HIV serostatus was unknowingly
      communicated. Partner exposures were equally distributed between steady and non
      steady partners. CONCLUSIONS: The probability of HIV exposure through condomless
      AI is substantially lower after serostatus disclosure compared to non-disclosure.
      Incorrect knowledge of one's HIV status contributes to a large proportion of HIV
      exposures amongst European MSM. Maintaining or improving condom use for anal
      intercourse with non-steady partners, frequent testing to update HIV serostatus
      awareness, and increased serostatus disclosure particularly between steady
      partners are confirmed as key aspects for reducing HIV exposures amongst European
      MSM.

PMID- 29178854
TI  - Subtrochanteric shortening osteotomy during cementless total hip arthroplasty in
      young patients with severe developmental dysplasia of the hip.
AB  - BACKGROUND: This retrospective study was designed to determine complications,
      functional and radiographic results of transverse subtrochanteric osteotomy
      during cementless, modular total hip arthroplasty (THA) in a series of active
      patients younger than 45 years with Crowe Type-III or IV developmental dysplasia
      of the hip (DDH). METHODS: We followed 49 patients (56 hips) with DDH who were
      treated with cementless THA, where the acetabular cup was positioned in the
      anatomic hip center and where a simultaneous transverse femoral osteotomy was
      performed. Complication rate evaluation and clinical outcomes were measured by
      validated clinical scores and radiographic evaluation were performed at a mean
      follow up of 10 years (range, 4.8-14.3 years). RESULTS: The mean limb-length
      discrepancy was reduced from 4.2 cm to 1.1 cm (P < 0.01). The mean Harris hip
      score (HSS) significantly improved from 40.6 points to 87.4 points (P < 0.01).
      Similarly, severity of low back pain, modified MAP, HOOS, and SF-12 also showed
      significant improvement (P < 0.01). There were 3 cases of postoperative
      dislocation, 3 cases of transient nerve palsy, 2 cases of nonunion, and 4 cases
      of intraoperative fracture. At 10 years follow-up, the estimated survival rate
      with any component revision as end points was 92%. CONCLUSION: The cementless THA
      combined with transverse subtrochanteric osteotomy is a reliable technique with
      restoration of a more normal limb, satisfactory clinical outcomes, and mid-term
      survival of components.

PMID- 29178855
TI  - Prices of over-the-counter drugs used by 15-year-old adolescents in Germany and
      their association with socioeconomic background.
AB  - BACKGROUND: In Germany, over-the-counter (OTC) drugs are normally reimbursed up
      to the age of 12 years only. The aim of this study was to analyse prices of over
      the-counter drugs used by adolescents in Germany and their association with
      socioeconomic factors. METHODS: Based on the German GINIplus and LISAplus birth
      cohorts, data on drug utilization among 15-year-old adolescents (n = 4677) were
      collected using a self-administered questionnaire. The reported drugs were
      subdivided into prescription drugs and OTC drugs. The drugs' prices were tracked
      by the pharmaceutical identification numbers. RESULTS: Overall, 1499 OTC drugs
      with clearly identifiable prices were eligible for analysis. Their mean price was
      ?9.75 (95% confidence interval: ?9.27-10.22). About 75% of the OTC drugs cost
      less than ?10. Higher mean prices were associated with residing in Munich
      (?10.74; 95% confidence interval: ?9.97-11.52) and with higher paternal education
      (e.g. highest education level: ?10.17; 95% confidence interval: ?9.47-10.86).
      Adolescents residing in Munich (in comparison with the less wealthy region of
      Wesel) and adolescents with higher educated fathers were also significantly more
      likely to use OTC drugs costing >= ?10 or >= ?25, respectively. CONCLUSIONS: The
      price of ?10 for non-reimbursable OTC drugs may represent a (psychological)
      threshold. Higher prices could discourage especially adolescents from a lower
      socioeconomic background from taking medically advisable but non-reimbursable OTC
      drugs.

PMID- 29178856
TI  - Influence of age on results following surgery for displaced acetabular fractures
      in the elderly.
AB  - BACKGROUND: Elderly patients have more special medical needs when compared with
      young ones; thus, the results of open reduction and internal fixation (ORIF) for
      acetabular fractures should be stratified by age in these patients. This study
      seeks to determine whether the age of the patient influences the results of the
      ORIF for acetabular fractures. METHODS: We performed a retrospective analysis of
      prospectively collected data on 53 elderly patients with displaced acetabular
      fractures who underwent ORIF between May 2004 and May 2011. Patients were divided
      into two groups by age: young-old group (60-74 years) and old-old group (75-90
      years). The number of patients in each group was 28 and 25. The reduction quality
      and clinical function was evaluated using the Matta criteria and modified Postel
      Merle D'Aubigne Score, respectively. Operative time, bleeding amount, and
      complications were recorded. RESULTS: Patients in old-old group had significantly
      lower anatomical reduction rate (p = 0.024), less operative time (p = 0.021), and
      less bleeding amount (p = 0.016) than those in the young-old group. The reduction
      quality in the young-old group was strongly associated with clinical function (p
      < 0.05). However, no difference in clinical function was detected among the
      different reduction qualities in the old-old group (p > 0.05). Moreover, no
      significant difference in clinical functions (p = 0.787) and complications (p =
      0.728) was detected between the two groups. CONCLUSIONS: Old-old patients may
      expect comparable clinical functions and complications with young-old patients.
      The reduction quality in old-old patients may be not significantly associated
      with clinical function. Different treatment strategies may be applied for
      acetabular fractures with ORIF in different age groups.

PMID- 29178857
TI  - Mini - social phobia inventory (mini-SPIN): psychometric properties and
      population based norms of the German version.
AB  - BACKGROUND: A short screening for social anxiety disorder is useful in clinical
      and epidemiological contexts. However, the German version of the short form of
      the Social Phobia Inventory (mini-SPIN) has not been evaluated yet. Therefore,
      our aim was to determine reliability, validity and population based norms of the
      German mini-SPIN. METHODS: The mini-SPIN was evaluated in a clinical (N = 1254)
      and in a representative community sample (N = 1274). Clinical diagnoses, the
      Patient Health Questionnaire depression (PHQ-9) and somatization modules (PHQ
      15), the Generalized Anxiety Disorder Scale (GAD-7), the Liebowitz Social Anxiety
      Scale (LSAS), and the Short-Form-12 Health Survey (SF-12) were used in the
      clinical sample. In the community sample, participants filled out socio
      demographic and health related questions and short versions of the PHQ (PHQ-2,
      GAD-2, panic item). Internal consistency, test-retest reliability, sensitivity to
      change, discriminant validity, and convergent validity were examined. Receiver
      operating characteristic curve analyses were performed to determine cut-off
      scores. Population based norms were computed from the community sample. RESULTS:
      We found internal consistencies between 0.80 and 0.83. Test-retest correlation
      was Rho = 0.61; sensitivity to change was comparable to the LSAS. Correlations
      indicated good convergent and discriminant validity of the mini-SPIN. Strict
      measurement invariance can be assumed regarding age and gender. Receiver
      operating characteristic curve analysis suggested a cut-off of 6 or higher for a
      probable diagnosis of SAD. CONCLUSIONS: The German version of the mini-SPIN is a
      reliable and valid instrument. Its brevity makes it valuable for screening and
      assessing changes of social anxiety in clinical and epidemiological studies.

PMID- 29178858
TI  - Measures of excess body weight and anthropometry among adult Albertans: cross
      sectional results from Alberta's tomorrow project cohort.
AB  - BACKGROUND: Excess body weight during adulthood has been consistently associated
      with all-cause mortality, cardiovascular disease, and cancer at multiple sites
      among other chronic diseases. We describe the prevalence of excess body weight
      and abdominal obesity reported by participants enrolled in Alberta's Tomorrow
      Project (ATP). METHODS: ATP is a geographically-based cohort study conducted
      among adults aged 35-69 years from across the province of Alberta. Participants
      completed anthropometric measures and health and lifestyle questionnaires at
      enrolment. Overweight and obese were categorized as a body mass index (BMI) of
      25.0-29.9 kg/m2 and >=30 kg/m2, respectively. Abdominal obesity was categorized
      using cut-offs of waist circumference of >94 cm for men and >80 cm for women and
      waist-tp-hip ratio cut-offs of >0.90 for men and >0.85 for women. RESULTS: BMI
      and hip and waist circumference data were obtained from 12,062 men and 18,853
      women enrolled between 2001 and 2009. Overall, 76.8% of men and 59.5% of women
      reported a BMI >=25 kg/m2. The proportions of overweight and obese were
      significantly higher in older age groups (p < 0.001). In addition, the proportion
      of participants reporting being overweight and obese was higher among lower
      education (p < 0.001) and lower income groups (p < 0.001). Overall, approximately
      two thirds of men and women in ATP cohort reported abdominal obesity. Overweight,
      obesity and abdominal obesity were all associated with a history of several
      cardiometabolic chronic conditions including hypertension, heart attack, angina,
      high cholesterol, stroke and diabetes. CONCLUSION: A large majority of ATP
      participants were overweight and carried excess abdominal fat. Strategies to
      improve energy balance among Albertans are encouraged and may have a notable
      impact on future chronic disease burden.

PMID- 29178859
TI  - Assessing the impact of the Lebanese National Polio Immunization Campaign using a
      population-based computational model.
AB  - BACKGROUND: After the re-introduction of poliovirus to Syria in 2013, Lebanon was
      considered at high transmission risk due to its proximity to Syria and the high
      number of Syrian refugees. However, after a large-scale national immunization
      initiative, Lebanon was able to prevent a potential outbreak of polio among
      nationals and refugees. In this work, we used a computational individual
      simulation model to assess the risk of poliovirus threat to Lebanon prior and
      after the immunization campaign and to quantitatively assess the healthcare
      impact of the campaign and the required standards that need to be maintained
      nationally to prevent a future outbreak. METHODS: Acute poliomyelitis
      surveillance in Lebanon was along with the design and coverage rate of the recent
      national polio immunization campaign were reviewed from the records of the
      Lebanese Ministry of Public Health. Lebanese population demographics including
      Syrian and Palestinian refugees were reviewed to design individual-based models
      that predicts the consequences of polio spread to Lebanon and evaluate the
      outcome of immunization campaigns. The model takes into account geographic,
      demographic and health-related features. RESULTS: Our simulations confirmed the
      high risk of polio outbreaks in Lebanon within 10 days of case introduction prior
      to the immunization campaign, and showed that the current immunization campaign
      significantly reduced the speed of the infection in the event poliomyelitis cases
      enter the country. A minimum of 90% national immunization coverage was found to
      be required to prevent exponential propagation of potential transmission.
      CONCLUSIONS: Both surveillance and immunization efforts should be maintained at
      high standards in Lebanon and other countries in the area to detect and limit any
      potential outbreak. The use of computational population simulation models can
      provide a quantitative approach to assess the impact of immunization campaigns
      and the burden of infectious diseases even in the context of population
      migration.

PMID- 29178860
TI  - A new classification of TKA periprosthetic femur fractures considering the
      implant type.
AB  - BACKGROUND: The treatment aims of periprosthetic fractures (PPF) of the distal
      femur are a gentle stabilization, an early load-bearing capacity and a rapid
      postoperative mobilization of the affected patients. For the therapy planning of
      PPF a standardized classification is necessary which leads to a clear and safe
      therapy recommendation. Despite different established classifications, there is
      none that includes the types of prosthesis used in the assessment. For this
      purpose, the objective of this work is to create a new more extensive fracture
      and implant-related classification of periprosthetic fractures of the distal
      femur based on available classifications which allows distinct therapeutic
      recommendations. METHODS: In a retrospective analysis all patients who were
      treated in the University Hospital Leipzig from 2010 to 2016 due to a distal
      femur fracture with total knee arthroplasty (TKA) were established. To create an
      implant-associated classification the cases were discussed in a panel of
      experienced orthopaedists and well-practiced traumatologists with a great
      knowledge in the field of endoprosthetics and fracture care. In this context, two
      experienced surgeons classified 55 consecutive fractures according to Su et al.,
      Lewis and Rorabeck and by the new created classification. In this regard, the
      interobserver reliability was determined for two independent raters in terms of
      Cohen Kappa. RESULTS: On the basis of the most widely recognized classifications
      of Su et al. as well as Lewis and Rorabeck, we established an implant-dependent
      classification for PPF of the distal femur. In accordance with the two stated
      classifications four fracture types were created and defined. Moreover, the four
      most frequent prosthesis types were integrated. Finally, a new classification
      with 16 subtypes was generated based on four types of fracture and four types of
      prosthesis. Considering all cases the presented implant-associated classification
      (kappa = 0.74) showed a considerably higher interobserver reliability compared to
      the other classifications of Su et al. (kappa = 0.39) as well as Lewis and
      Rorabeck (kappa = 0.31). Excluding the cases which were only assessable by the
      new classification, it still shows a higher interobserver reliability (kappa =
      0.70) than the other ones (kappa = 0.63 or kappa = 0.45). CONCLUSIONS: The new
      classification system for PPF of the distal femur following TKA considers
      fracture location and implant type. It is easy to use, shows agood interobserver
      reliability and allows conclusions to be drawn on treatment recommendations.
      Moreover, further studies on the evaluation of the classification are necessary
      and planned.

PMID- 29178861
TI  - Contact stresses, pressure and area in a fixed-bearing total ankle replacement: a
      finite element analysis.
AB  - BACKGROUND: Mobile-bearing ankle implants with good clinical results continued to
      increase the popularity of total ankle arthroplasty to address endstage ankle
      osteoarthritis preserving joint movement. Alternative solutions used fixed
      bearing designs, which increase stability and reduce the risk of bearing
      dislocation, but with a theoretical increase of contact stresses leading to a
      higher polyethylene wear. The purpose of this study was to investigate the
      contact stresses, pressure and area in the polyethylene component of a new total
      ankle replacement with a fixed-bearing design, using 3D finite element analysis.
      METHODS: A three-dimensional finite element model of the Zimmer Trabecular Metal
      Total Ankle was developed and assembled based on computed tomography images.
      Three different sizes of the polyethylene insert were modeled, and a finite
      element analysis was conducted to investigate the contact pressure, the von Mises
      stresses and the contact area of the polyethylene component during the stance
      phase of the gait cycle. RESULTS: The peak value of pressure was found in the
      anterior region of the articulating surface, where it reached 19.8 MPa at 40% of
      the gait cycle. The average contact pressure during the stance phase was 6.9 MPa.
      The maximum von Mises stress of 14.1 MPa was reached at 40% of the gait cycle in
      the anterior section. In the central section, the maximum von Mises stress of
      10.8 MPa was reached at 37% of the gait cycle, whereas in the posterior section
      the maximum stress of 5.4 MPa was reached at the end of the stance phase.
      DISCUSSION: The new fixed-bearing total ankle replacement showed a safe
      mechanical behavior and many clinical advantages. However, advanced models to
      quantitatively estimate the wear are need. CONCLUSION: To the light of the
      clinical advantages, we conclude that the presented prosthesis is a good
      alternative to the other products present in the market.

PMID- 29178863
TI  - Estimating disease burden of a potential A(H7N9) pandemic influenza outbreak in
      the United States.
AB  - BACKGROUND: Since spring 2013, periodic emergence of avian influenza A(H7N9)
      virus in China has heightened the concern for a possible pandemic outbreak among
      humans, though it is believed that the virus is not yet human-to-human
      transmittable. Till June 2017, A(H7N9) has resulted in 1533 laboratory-confirmed
      cases of human infections causing 592 deaths. The aim of this paper is to present
      disease burden estimates (measured by infection attack rates (IAR) and number of
      deaths) in the event of a possible pandemic outbreak caused by human-to-human
      transmission capability acquired by A(H7N9) virus. Even though such a pandemic
      will likely spread worldwide, our focus in this paper is to estimate the impact
      on the United States alone. METHOD: The method first uses a data clustering
      technique to divide 50 states in the U.S. into a small number of clusters.
      Thereafter, for a few selected states in each cluster, the method employs an
      agent-based (AB) model to simulate human A(H7N9) influenza pandemic outbreaks.
      The model uses demographic and epidemiological data. A few selected non
      pharmaceutical intervention (NPI) measures are applied to mitigate the outbreaks.
      Disease burden for the U.S. is estimated by combining results from the clusters
      applying a method used in stratified sampling. RESULTS: Two possible pandemic
      scenarios with R 0 = 1.5 and 1.8 are examined. Infection attack rates with 95%
      C.I. (Confidence Interval) for R 0 = 1.5 and 1.8 are estimated to be 18.78% (17.3
      20.27) and 25.05% (23.11-26.99), respectively. The corresponding number of deaths
      (95% C.I.), per 100,000, are 7252.3 (6598.45-7907.33) and 9670.99 (8953.66
      10,389.95). CONCLUSIONS: The results reflect a possible worst-case scenario where
      the outbreak extends over all states of the U.S. and antivirals and vaccines are
      not administered. Our disease burden estimations are also likely to be somewhat
      high due to the fact that only dense urban regions covering approximately 3% of
      the geographic area and 81% of the population are used for simulating sample
      outbreaks. Outcomes from these simulations are extrapolated over the remaining
      19% of the population spread sparsely over 97% of the area. Furthermore, the full
      extent of possible NPIs, if deployed, could also have lowered the disease burden
      estimates.

PMID- 29178862
TI  - Prevalence and types of high-risk human papillomaviruses in head and neck cancers
      from Bangladesh.
AB  - BACKGROUND: There is a dramatic rise in the incidence of Human papillomavirus
      (HPV) - associated head and neck squamous cell carcinoma (HNSCC) in the world,
      with considerable variation by geography, gender and ethnicity. Little is known
      about the situation in Bangladesh, where tobacco- and areca nut-related head and
      neck cancers (HNCs) are the most common cancers in men. We aimed to determine the
      prevalence of HPV in HNSCC in Bangladesh and to explore the possible value of
      cell cycle markers in clinical diagnostic settings. METHODS: One hundred and
      ninety six archival HNSCC tissue samples were analysed for the presence of HPV
      DNA. The DNA quality was assured, and then amplified using a nested PCR approach.
      The typing of HPV was performed by automated DNA sequencing. Cellular markers
      p53, Cyclin D1 and pRb were tested on all samples by immunohistochemistry (IHC),
      as well as p16 as a putative surrogate for the detection of HPV. RESULTS: HPV DNA
      was detected in 36/174 (~21%) samples: 36% of cancers from the oropharynx; 31% of
      oral cancers, and 22% from the larynx. HPV-16 was most common, being present in
      33 samples, followed by HPV-33 (2 samples) and HPV-31 (1 sample). Twenty-eight
      out of 174 samples were positive for p16, predominantly in HPV-positive tissues
      (p < 0.001). No statistically significant association was observed between the
      cellular markers and HPV DNA positive cases. However, p16 positivity had
      excellent predictive value for the presence of HPV by PCR. CONCLUSION: There is a
      significant burden of HPV-associated HNSCC in Bangladesh, particularly in the
      oropharynx but also in oral and laryngeal cancers. Whilst a combination of PCR
      based DNA detection and p16 IHC is useful, the latter has excellent specificity,
      acceptable sensitivity and good predictive value for carriage of HPV in this
      population and should be used for prognostic evaluation and treatment planning of
      all HNSCC patients in South Asia, as in the Western world.

PMID- 29178864
TI  - Musculoskeletal extremity pain in Danish school children - how often and for how
      long? The CHAMPS study-DK.
AB  - BACKGROUND: Musculoskeletal pain is common in childhood and adolescence, and may
      be long-lasting and recurrent. Musculoskeletal problems tend to follow
      adolescents into adulthood, and therefore it is important to design better
      prevention strategies and early effective treatment. To this end, we need in
      depth knowledge about the epidemiology of musculoskeletal extremity problems in
      this age group, and therefore, the aim of this study was to determine the
      prevalence, frequency and course of musculoskeletal pain in the upper and lower
      extremities in a cohort of Danish school children aged 8-14 years at baseline.
      METHODS: This was a prospective 3-year school-based cohort study, with
      information about musculoskeletal pain collected in two ways. Parents answered
      weekly mobile phone text messages about the presence or absence of
      musculoskeletal pain in their children, and a clinical consultation was performed
      in a subset of the children. RESULTS: We found that approximately half the
      children had lower extremity pain every study year. This pain lasted on average
      for 8 weeks out of a study year, and the children had on average two and a half
      episodes per study year. Approximately one quarter of the children had upper
      extremity pain every study year that lasted on average 3 weeks during a study
      year, with one and a half episodes being the average. In general, there were more
      non-traumatic pain episodes compared with traumatic episodes in the lower
      extremities, whereas the opposite was true in the upper extremities. The most
      common anatomical pain sites were 'knee' and 'ankle/ft'. CONCLUSION: Lower
      extremity pain among children and adolescents is common, recurrent and most often
      of non-traumatic origin. Upper extremity pain is less common, with fewer and
      shorter episodes, and usually with a traumatic onset. Girls more frequently
      reported upper extremity pain, whereas there was no sex-related difference in the
      lower extremities. The most frequently reported locations were 'knee' and
      'ankle/ft'.

PMID- 29178865
TI  - Palliative care for patients with Parkinson's disease: study protocol for a mixed
      methods study.
AB  - BACKGROUND: Parkinson's disease (PD) is a chronic, progressive neurological
      disorder with many intractable consequences for patients and their family
      caregivers. Little is known about the possibilities that palliative care could
      offer to patients and their proxies. Guidelines strongly recommend palliative
      care to improve the quality of life and - if needed - the quality of dying.
      However, providing palliative care to persons with PD involves specific
      challenges. For example, a timely initiation of palliative interventions is
      difficult because due to the gradually progressive nature of PD, there is often
      no clear marker for the transition from curative towards palliative care.
      Furthermore, there is little evidence to indicate which palliative care
      interventions are effective. Here, we describe the contours of a study that aims
      to examine the experiences of patients, (bereaved) family caregivers and
      professionals, with the aim of improving our knowledge about palliative care
      needs in PD. METHODS/DESIGN: We will perform a mixed methods study to evaluate
      the experiences of patients, (bereaved) family caregivers and palliative care
      professionals. In this study, we focus on Quality of Life, Quality of Care,
      perceived symptoms, caregiver burden and collaboration between professionals. In
      phase 1, we will retrospectively explore the views of bereaved family caregivers
      and professionals by conducting individual interviews and focus group interviews.
      In phase 2, 5-15 patients with PD and their family caregiver will be followed
      prospectively for 8-12 months. Data collection will involve semi-structured
      interviews and questionnaires at three consecutive contact moments. Qualitative
      data will be audio recorded, transcribed and analyzed using CAQDAS. If patients
      pass away during the study period, a bereavement interview will be done with the
      closest family caregiver. DISCUSSION: This study will offer a broad perspective
      on palliative care, and the results can be used to inform a palliative care
      protocol for patients with PD. By describing the experiences of patients,
      (bereaved) family caregivers and professionals with palliative care, this
      investigation will also establish an important ground for future intervention
      research.

PMID- 29178866
TI  - A scoping review of palliative care for children in low- and middle-income
      countries.
AB  - BACKGROUND: Ninety-eight percent of children needing palliative care live in low-
      and middle-income countries (LMICs), and almost half of them live in Africa. In
      contrast to the abundance of data on populations in high income countries, the
      current data on populations in LMICs is woefully inadequate. This study aims to
      identify and summarize the published literature on the need, accessibility,
      quality, and models for palliative care for children in LMICs. METHODS: A scoping
      review was performed following the method of Arksey and O'Malley. Systematic
      searches were conducted on PubMed and Google Scholar using the main keywords,
      'children AND palliative care OR terminal care OR hospice OR end of life AND
      developing countries OR LMICs.' Additional publications were obtained by
      handsearching. Papers were only included if they reported on the need,
      accessibility, quality, and models for palliative care for children in LMICs.
      RESULTS: Fifteen papers met the inclusion criteria for review. Of these, 10
      assessed need, seven examined availability and/or accessibility, one assessed
      quality, and one examined the models. We found an urgent need for palliative
      care, particularly in the training for health workers and improving poor
      availability and/or accessibility to palliative care in terms of factors such as
      medication and bereavement support. The best practice models demonstrated
      feasibility and sustainability through cooperation with governments and community
      organizations. The quality of pain management and emotional support was lower in
      LMICs compared to HICs. CONCLUSION: Although we found limited evidence in this
      review, we identified common challenges such as the need for further training for
      health workers and greater availability of opioid analgesics. While efforts to
      change the current systems and laws applying to children in LMICs are important,
      we should also tackle underlying factors including the need to raise awareness
      about palliative care in public health and improve the accuracy of data
      collection.

PMID- 29178867
TI  - Does objectively measured physical activity modify the association between early
      weight gain and fat mass in young adulthood?
AB  - BACKGROUND: Substantial evidence suggests that weight gain in early life is
      associated with increased adiposity and other metabolic disorders later in life.
      It is, however, unknown whether physical activity (PA) may modify these
      associations. We aimed to examine whether objectively measured PA at 30 years
      modified the associations between conditional weight gain in infancy (0-2 y) and
      childhood (2-4 y) with fat mass index (FMI) and visceral abdominal fat measured
      at age 30 years. METHODS: Prospective birth cohort study in Pelotas, Brazil,
      including 1874 participants with weight data at birth, two and four years of age,
      and measures of FMI, visceral abdominal fat and PA at a mean age of 30.2 years.
      At age 30, time spent (min/day) in moderate-to-vigorous physical activity (MVPA)
      was measured objectively using a wrist-worn accelerometer worn for four to seven
      consecutive days.. Multiple linear regression analyses was performed to assess
      the associations between conditional weight gain and outcome variables at 30
      years, adjusting for covariates. We examined whether PA modified the association
      between conditional weight gain and the outcomes of interest by introducing an
      interaction term (conditional weight gain * PA) in the models. RESULTS:
      Conditional weight gain in infancy and childhood were both positively associated
      with later FMI (infancy weight gain: beta = 0.68, 95% CI: 0.48, 0.88; P < 0.001;
      childhood weight gain: beta = 0.91, 95% CI: 0.70, 1.11; P < 0.001). A formal test
      for interaction suggested that MVPA at 30 years of age modified the association
      between childhood relative weight gain and later FMI (beta = -0.006, 95% CI: 
      0.011, -0.001; P = 0.029), suggesting stronger associations between weight gain
      and FMI in those with lower levels of MVPA. Conditional weight gain in childhood
      was also positively associated with visceral abdominal fat (beta = 0.24, 95% CI:
      0.15, 0424, P < 0.001). There was no evidence for a modification of the latter
      association after adjustment for physical activity. CONCLUSION: Conditional
      weight gain between 2 and 4 years of age is associated with increased FMI at age
      30 years. However, higher levels of MVPA appear to attenuate this detrimental
      association.

PMID- 29178868
TI  - Derivation and validation of the Personal Support Algorithm: an evidence-based
      framework to inform allocation of personal support services in home and community
      care.
AB  - BACKGROUND: Personal support services enable many individuals to stay in their
      homes, but there are no standard ways to classify need for functional support in
      home and community care settings. The goal of this project was to develop an
      evidence-based clinical tool to inform service planning while allowing for
      flexibility in care coordinator judgment in response to patient and family
      circumstances. METHODS: The sample included 128,169 Ontario home care patients
      assessed in 2013 and 25,800 Ontario community support clients assessed between
      2014 and 2016. Independent variables were drawn from the Resident Assessment
      Instrument-Home Care and interRAI Community Health Assessment that are
      standardised, comprehensive, and fully compatible clinical assessments. Clinical
      expertise and regression analyses identified candidate variables that were
      entered into decision tree models. The primary dependent variable was the weekly
      hours of personal support calculated based on the record of billed services.
      RESULTS: The Personal Support Algorithm classified need for personal support into
      six groups with a 32-fold difference in average billed hours of personal support
      services between the highest and lowest group. The algorithm explained 30.8% of
      the variability in billed personal support services. Care coordinators and
      managers reported that the guidelines based on the algorithm classification were
      consistent with their clinical judgment and current practice. CONCLUSIONS: The
      Personal Support Algorithm provides a structured yet flexible decision-support
      framework that may facilitate a more transparent and equitable approach to the
      allocation of personal support services.

PMID- 29178869
TI  - The potential impact of food taxes and subsidies on cardiovascular disease and
      diabetes burden and disparities in the United States.
AB  - BACKGROUND: Fiscal interventions are promising strategies to improve diets,
      reduce cardiovascular disease and diabetes (cardiometabolic diseases; CMD), and
      address health disparities. The aim of this study is to estimate the impact of
      specific dietary taxes and subsidies on CMD deaths and disparities in the US.
      METHODS: Using nationally representative data, we used a comparative risk
      assessment to model the potential effects on total CMD deaths and disparities of
      price subsidies (10%, 30%) on fruits, vegetables, whole grains, and nuts/seeds
      and taxes (10%, 30%) on processed meat, unprocessed red meats, and sugar
      sweetened beverages. We modeled two gradients of price-responsiveness by
      education, an indicator of socioeconomic status (SES), based on global price
      elasticities (18% greater price-responsiveness in low vs. high SES) and recent
      national experiences with taxes on sugar-sweetened beverages (65% greater price
      responsiveness in low vs. high SES). RESULTS: Each price intervention would
      reduce CMD deaths. Overall, the largest proportional reductions were seen in
      stroke, followed by diabetes and coronary heart disease. Jointly altering prices
      of all seven dietary factors (10% each, with 18% greater price-responsiveness by
      SES) would prevent 23,174 (95% UI 22,024-24,595) CMD deaths/year, corresponding
      to 3.1% (95% UI 2.9-3.4) of CMD deaths among Americans with a lower than high
      school education, 3.6% (95% UI 3.3-3.8) among high school graduates/some college,
      and 2.9% (95% UI 2.7-3.5) among college graduates. Applying a 30% price change
      and larger price-responsiveness (65%) in low SES, the corresponding reductions
      were 10.9% (95% UI 9.2-10.8), 9.8% (95% UI 9.1-10.4), and 6.7% (95% UI 6.2-7.6).
      The latter scenario would reduce disparities in CMD between Americans with lower
      than high school versus a college education by 3.5 (95% UI 2.3-4.5) percentage
      points. CONCLUSIONS: Modest taxes and subsidies for key dietary factors could
      meaningfully reduce CMD and improve US disparities.

PMID- 29178870
TI  - Clinical factors contributing to high cost hospitalizations in a Canadian
      tertiary care centre.
AB  - BACKGROUND: Like much of the developed world, healthcare costs in Canada are
      rising. A small proportion of patients account for a large proportion of
      healthcare spending and much of this spending occurs in acute care settings. The
      purpose of our study was to determine potentially modifiable factors related to
      care processes that contribute to high-cost admissions. METHODS: Using a mixed
      methods study design, factors contributing to high-cost admissions were
      identified from literature and case review. We defined pre- and post-admission
      factors contributing to high-cost admissions. Pre-admission factors included
      reason for admission (e.g. complex medical, elective surgery, trauma, etc.). Post
      admission factors included medical complications, disposition delays, clinical
      services delays, and inefficient clinical decision-making. We selected a random
      sample of admissions in the top decile of inpatient cost from the Ottawa Hospital
      between January 1 and December 31, 2010. A single reviewer classified cases based
      on the pre- and post-admission factors. We combined this information with data
      derived from the Ottawa Hospital Data Warehouse to describe patient-level
      clinical and demographic characteristics and costs incurred. RESULTS: We reviewed
      200 charts which represents ~5% of all high cost admissions within the Ottawa
      Hospital in 2010. Post-admission factors contributing to high-cost admissions
      were: complications (60%), disposition delays (53%), clinical service delays
      (39%), and inefficient clinical decision-making (13%). Further, these factors
      varied substantially across service delivery lines. The mean (standard deviation
      (SD)) cost per admission was $49,923 CDN ($45,773). The most common reason for
      admission was "complex medical" (49%) and the overall median (IQR) length of stay
      was 27 (18-48) days. Approximately 1 in 3 high cost admissions (29%) included
      time in the intensive care unit (ICU). CONCLUSIONS: While high cost admissions
      often include time in ICU and have long lengths of stay, a substantial proportion
      of costs were attributable to complications and potentially preventable delays in
      care processes. These findings suggest opportunities exist to improve outcomes
      and reduce costs for this diverse patient population.

PMID- 29178871
TI  - Efficacy and safety of tiotropium and olodaterol in COPD: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Long-acting bronchodilators are the cornerstone of pharmacologic
      treatment of COPD. The new combination of long-acting muscarinic antagonist
      (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has
      been introduced as fist line therapy for COPD. This article analyses the evidence
      of efficacy and safety of the TIO/OLO combination. METHODS: A systematic review
      and metaanalysis of randomized controlled trials (RCT) with a period of treatment
      of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing
      combined treatment with TIO/OLO (approved doses only), with any of the mono
      components or any other active comparator administered as an inhalator. RESULTS:
      A total of 10 Randomized controlled trials (RCT) were identified (N = 10,918).
      TIO/OLO significantly improved trough FEV1 from baseline to week 12 versus TIO,
      OLO and LABA/ICS (0.06 L, 0.09 L and between 0.04 and 0.05 L, respectively).
      TIO/OLO improved transitional dyspnea index (TDI) and St. George's Respiratory
      Questionnaire (SGRQ) compared with mono-components, with patients more likely to
      achieve clinically important improvements in TDI (risk ratio [RR]: 1.17, 95%
      confidence interval [CI]: [1.07, 1.28] versus TIO and RR: 1.14, 95%CI: [1.01,
      1.28] versus OLO) and in SGRQ (RR: 1.21, 95%CI: [1.12, 1.30] versus TIO and RR:
      1.28, 95%CI: [1.18, 1.40] versus OLO). Patients treated with TIO/OLO showed a
      significant reduction in the use of rescue medication and no significant
      differences in frequency of general and serious adverse events were observed
      between TIO/OLO and mono-components. CONCLUSIONS: Treatment with TIO/OLO provided
      significant improvements in lung function versus mono-components and LABA/ICS
      with more patients achieving significant improvements in dyspnea and health
      status. No differences in adverse events were observed compared with other active
      treatments. CLINICAL TRIAL REGISTRATION: PROSPERO register of systematic reviews
      ( CRD42016040162 ).

PMID- 29178872
TI  - MitoCore: a curated constraint-based model for simulating human central
      metabolism.
AB  - BACKGROUND: The complexity of metabolic networks can make the origin and impact
      of changes in central metabolism occurring during diseases difficult to
      understand. Computer simulations can help unravel this complexity, and progress
      has advanced in genome-scale metabolic models. However, many models produce
      unrealistic results when challenged to simulate abnormal metabolism as they
      include incorrect specification and localisation of reactions and transport
      steps, incorrect reaction parameters, and confounding of prosthetic groups and
      free metabolites in reactions. Other common drawbacks are due to their scale,
      making them difficult to parameterise and simulation results hard to interpret.
      Therefore, it remains important to develop smaller, manually curated models.
      RESULTS: We present MitoCore, a manually curated constraint-based computer model
      of human metabolism that incorporates the complexity of central metabolism and
      simulates this metabolism successfully under normal and abnormal physiological
      conditions, including hypoxia and mitochondrial diseases. MitoCore describes 324
      metabolic reactions, 83 transport steps between mitochondrion and cytosol, and 74
      metabolite inputs and outputs through the plasma membrane, to produce a model of
      manageable scale for easy interpretation of results. Its key innovations include
      a more accurate partitioning of metabolism between cytosol and mitochondrial
      matrix; better modelling of connecting transport steps; differentiation of
      prosthetic groups and free co-factors in reactions; and a new representation of
      the respiratory chain and the proton motive force. MitoCore's default parameters
      simulate normal cardiomyocyte metabolism, and to improve usability and allow
      comparison with other models and types of analysis, its reactions and metabolites
      have extensive annotation, and cross-reference identifiers from Virtual Metabolic
      Human database and KEGG. These innovations-including over 100 reactions absent or
      modified from Recon 2-are necessary to model central metabolism more accurately.
      CONCLUSION: We anticipate MitoCore as a research tool for scientists, from
      experimentalists looking to interpret their data and test hypotheses, to
      experienced modellers predicting the consequences of disease or using
      computationally intensive methods that are infeasible with larger models, as well
      as a teaching tool for those new to modelling and needing a small, manageable
      model on which to learn and experiment.

PMID- 29178873
TI  - Prevalence and molecular characterization of Staphylococcus aureus isolated from
      goats in Chongqing, China.
AB  - BACKGROUND: Staphylococcus aureus is an important zoonotic pathogen which not
      only causes significant economic loss in livestock production but also poses a
      potential threat to public health. Compared with bovine and swine, the
      information on the colonization of S. aureus in goats is very limited. To
      understand the prevalence and characteristics of S. aureus in goats, we used the
      nasal swabs collected from apparently healthy goats to isolate S. aureus, and
      tested their antimicrobial susceptibility, virulence gene carrying levels, and
      multilocus sequence typing (MLST). RESULTS: In 74 nasal swabs of apparently
      healthy goats, 32 (43.24%) S. aureus strains were isolated and identified, most
      of which were susceptible to many antibiotics, except for trimethoprim,
      furazolidone, amoxicillin, lincomycin and roxithromycin, and the resistance
      incidence of which were 50%, 40.63%, 37.5%, 28.13%, and 21.88% respectively. All
      the isolates were methicillin-susceptible S. aureus (MSSA) and mecA-negative.
      Enterotoxin genes were found in 53.13% of the strains. Of which, sej was the most
      prevalent (21.88%), followed by seb, sec, and see with the same level (18.75%).
      The most prevalent combination were seb + see and seb + tst. None of the S.
      aureus isolates harbored sea, sed, seh, eta and etb. Multilocus sequence typing
      (MLST) revealed 6 new alleles (aroe-552, aroe-553, glpf-500, pta-440, yqil-482
      and yqil-496) and 5 new sequence types (STs) (3431,3440,3444,3445 and 3461).
      Using eBURST, the 5 STs were assigned to clonal complex 522 (CC522) and a further
      CC with no predicted ancestor. Phylogenetic analysis of seven concatenated MLST
      alleles revealed that the 5 STs were grouped into cluster I composed of S. aureus
      mainly from goats and sheep. CONCLUSION: We provide the data for prevalence of S.
      aureus in goats in Chongqing municipality and their characterization which will
      help in tracking evolution of epidemic strains and their control methods.

PMID- 29178874
TI  - Reference gene validation for gene expression normalization in canine
      osteosarcoma: a geNorm algorithm approach.
AB  - BACKGROUND: Quantitative PCR (qPCR) is a common method for quantifying mRNA
      expression. Given the heterogeneity present in tumor tissues, it is crucial to
      normalize target mRNA expression data using appropriate reference genes that are
      stably expressed under a variety of pathological and experimental conditions. No
      studies have validated specific reference genes in canine osteosarcoma (OS).
      Previous gene expression studies involving canine OS have used one or two
      reference genes to normalize gene expression. This study aimed to validate a
      panel of reference genes commonly used for normalization of canine OS gene
      expression data using the geNorm algorithm. qPCR analysis of nine canine
      reference genes was performed on 40 snap-frozen primary OS tumors and seven cell
      lines. RESULTS: Tumors with a variety of clinical and pathological
      characteristics were selected. Gene expression stability and the optimal number
      of reference genes for gene expression normalization were calculated. RPS5 and
      HNRNPH were highly stable among OS cell lines, while RPS5 and RPS19 were the best
      combination for primary tumors. Pairwise variation analysis recommended four and
      two reference genes for optimal normalization of the expression data of canine OS
      tumors and cell lines, respectively. CONCLUSIONS: Appropriate combinations of
      reference genes are recommended to normalize mRNA levels in canine OS tumors and
      cell lines to facilitate standardized and reliable quantification of target gene
      expression, which is essential for investigating key genes involved in canine OS
      metastasis and for comparative biomarker discovery.

PMID- 29178875
TI  - Metabolic engineering of Synechococcus elongatus PCC 7942 for improvement of 1,3
      propanediol and glycerol production based on in silico simulation of metabolic
      flux distribution.
AB  - BACKGROUND: Production directly from carbon dioxide by engineered cyanobacteria
      is one of the promising technologies for sustainable future. Previously, we have
      successfully achieved 1,3-propanediol (1,3-PDO) production using Synechococcus
      elongatus PCC 7942 with a synthetic metabolic pathway. The strain into which the
      synthetic metabolic pathway was introduced produced 3.48 mM (0.265 g/L) 1,3-PDO
      and 14.3 mM (1.32 g/L) glycerol during 20 days of incubation. In this study, the
      productivities of 1,3-PDO were improved by gene disruption selected by screening
      with in silico simulation. METHODS: First, a stoichiometric metabolic model was
      applied to prediction of cellular metabolic flux distribution in a 1,3-PDO
      producing strain of S. elongatus PCC 7942. A genome-scale model of S. elongatus
      PCC 7942 constructed by Knoop was modified by the addition of a synthetic
      metabolic pathway for 1,3-PDO production. Next, the metabolic flux distribution
      predicted by metabolic flux balance analysis (FBA) was used for in silico
      simulation of gene disruption. As a result of gene disruption simulation, NADPH
      dehydrogenase 1 (NDH-1) complexes were found by screening to be the most
      promising candidates for disruption to improve 1,3-PDO production. The effect of
      disruption of the gene encoding a subunit of the NDH-1 complex was evaluated in
      the 1,3-PDO-producing strain. RESULTS AND CONCLUSIONS: During 20 days of
      incubation, the ndhF1-null 1,3-PDO-producing strain showed the highest titers:
      4.44 mM (0.338 g/L) 1,3-PDO and 30.3 mM (2.79 g/L) glycerol. In this study, we
      successfully improved 1,3-PDO productivity on the basis of in silico simulation
      of gene disruption.

PMID- 29178876
TI  - Urban-rural difference in satisfaction with primary healthcare services in Ghana.
AB  - BACKGROUND: Understanding regional variation in patient satisfaction about
      healthcare systems (PHCs) on the quality of services provided is instrumental to
      improving quality and developing a patient-centered healthcare system by making
      it more responsive especially to the cultural aspects of health demands of a
      population. Reaching to the innovative National Health Insurance Scheme (NHIS) in
      Ghana, surpassing several reforms in healthcare financing has been a milestone.
      However, the focus of NHIS is on the demand side of healthcare delivery. Studies
      focusing on the supply side of healthcare delivery, particularly the quality of
      service as perceived by the consumers are required. A growing number of studies
      have focused on regional differences of patient satisfaction in developed
      countries, however little research has been conducted concerning patient
      satisfaction in resource-poor settings like in Ghana. This study was therefore
      dedicated to examining the variation in satisfaction across rural and urban women
      in Ghana. METHODS: Data for the present study were obtained from the latest
      demographic and health survey in Ghana (GDHS 2014). Participants were 3576 women
      aged between 15 and 49 years living in non-institutional settings in Ghana.
      Summary statistics in percentages was used to present respondents' demographic,
      socioeconomic characteristics. Chi-square test was used to find association
      between urban-rural differentials with socio-economic variables. Multiple
      logistic regression was performed to measure the association of being satisfied
      with primary healthcare services with study variables. Model fitness was tested
      by pseudo R 2. Statistical significance was set at p < 0.05. RESULTS: The
      findings in this study revealed that about 57.1% were satisfied with primary
      health care services. The urban and rural areas reported 57.6 and 56.6%
      respectively which showed no statistically significant difference (z = 0.64; p =
      0.523; 95%CI: -0.022, 0.043). Bivariate analysis showed that region, highest
      level of education, wealth index and type of facility were significantly
      associated with location of residence (urban-rural areas). After adjusting for
      confounding variables using logistic regression, geographical location became a
      key factor of satisfaction with primary healthcare services by location of
      residence. In urban areas, respondents from Greater Accra had 64% increase in the
      level of satisfaction when compared to those in Western region (OR = 1.64; 95CI:
      1.09-2.47), Upper East had 75% increase in satisfaction compared to Western
      region (OR = 1.75; 95%CI: 1.08-2.84), Northern had an estimated 44% reduction in
      satisfaction when compared to Western region (OR = 0.56; 95%CI: 0.34-0.92).
      However, rural areas in Central, Volta, Eastern, Ashanti, Brong Aghafo, Northern
      and Upper West region had 51, 81, 69, 46, 62, 75 and 61% reduction respectively
      in the level of satisfaction when compared to Western region. CONCLUSIONS:
      Patient satisfaction is an important indicator of health outcomes. Quality of
      care and measuring level of patient satisfaction has been found to be the most
      useful tool to predict utilization and compliance. In fact, satisfied patients
      are more likely than unsatisfied ones to continue using health care services. Our
      results suggest that policymakers need to better understand the determinants of
      satisfaction with the health system and how different socio-demographic groups
      perceive satisfaction with healthcare services so as to address health
      inequalities between urban and rural areas within the same country.

PMID- 29178877
TI  - Non-sterilized fermentation of high optically pure D-lactic acid by a genetically
      modified thermophilic Bacillus coagulans strain.
AB  - BACKGROUND: Optically pure D-lactic acid (>= 99%) is an important precursor of
      polylactic acid. However, there are relatively few studies on D-lactic acid
      fermentation compared with the extensive investigation of L-lactic acid
      production. Most lactic acid producers are mesophilic organisms. Optically pure D
      lactic acid produced at high temperature not only could reduce the costs of
      sterilization but also could inhibit the growth of other bacteria, such as L
      lactic acid producers. RESULTS: Thermophilic Bacillus coagulans is an excellent
      producer of L-lactic acid with capable of growing at 50  degrees C. In our
      previous study, the roles of two L-lactic acid dehydrogenases have been
      demonstrated in B. coagulans DSM1. In this study, the function of another
      annotated possible L-lactate dehydrogenase gene (ldhL3) was verified to be
      leucine dehydrogenase with an activity of 0.16 units (MUmol/min) per mg protein.
      Furthermore, the activity of native D-lactate dehydrogenase was too low to
      support efficient D-lactic acid production, even under the control of strong
      promoter. Finally, an engineered B. coagulans D-DSM1 strain with the capacity for
      efficient production of D-lactic acid was constructed by deletion of two L
      lactate dehydrogenases genes (ldhL1 and ldhL2) and insertion of the D-lactate
      dehydrogenase gene (LdldhD) from Lactobacillus delbrueckii subsp. bulgaricus DSM
      20081 at the position of ldhL1. CONCLUSIONS: This genetically engineered strain
      produced only D-lactic acid under non-sterilized condition, and finally 145 g/L
      of D-lactic acid was produced with an optical purity of 99.9% and a high yield of
      0.98 g/g. This is the highest optically pure D-lactic acid titer produced by a
      thermophilic strain.

PMID- 29178878
TI  - Trypsin-independent porcine epidemic diarrhea virus US strain with altered virus
      entry mechanism.
AB  - BACKGROUND: Porcine Epidemic Diarrhea Virus (PEDV) is a coronavirus that infects
      the intestinal tract and causes diarrhea and vomiting in older pigs or extreme
      dehydration and death that could reach 100% mortality in neonatal piglets. In the
      US, the first PEDV outbreaks occurred in 2013 and since then US PEDV strains have
      quickly spread throughout the US and worldwide, causing significant economic and
      public health concerns. Currently two conditionally approved vaccines exist in
      the US, but there is no live attenuated vaccine, which is considered the best
      option in controlling PEDV by inducing transferrable mucosal immunity to
      susceptible neonatal piglets. In this study, we passaged an US PEDV isolate under
      various conditions to generate three strains and characterized their growth and
      antigenicity in cell culture using various assays including Western blot
      analysis, serum neutralization assay, sequencing analysis and confocal
      microscopy. Finally, these strains were evaluated for pathogenicity in nursing
      piglets (1-4 days old). RESULTS: One of the PEDV strains generated in this study
      (designated as PEDV 8aa) is able to replicate in cells without any protease and
      grows to a high titer of >8 log10 TCID50/ml in cell culture. Interestingly,
      replication of PEDV 8aa was severely reduced by trypsin and this correlated with
      the inhibition of virus attachment and entry into the cells. In neonatal nursing
      piglets, PEDV 8aa (passage number 70 or 105) was found to be fully attenuated
      with limited virus shedding. CONCLUSIONS: These results suggest that applying
      selective pressure during viral passages can facilitate attainment of viral
      attenuation and that PEDV 8aa warrants further investigation as an attenuated
      vaccine.

PMID- 29178879
TI  - Residual renal function in chronic dialysis is not associated with reduced
      erythropoietin-stimulating agent dose requirements: a cross-sectional study.
AB  - BACKGROUND: Anaemia is a very common problem in patients with end-stage kidney
      disease (ESKD) and the use of erythropoietin-stimulating agents (ESA) has
      revolutionised its treatment. Residual renal function (RRF) is associated with a
      reduction in ESA resistance and mortality in chronic dialysis. The primary aim
      was to establish whether RRF has an association with ESA dose requirements in
      ESKD patients receiving chronic dialysis. METHODS: A single center, cross
      sectional study involving 100 chronic dialysis patients was conducted from
      December 2015 to May 2016. Participants were divided into two groups depending on
      presence of RRF, which was defined as a 24-h urine sample volume of >= 100 ml.
      Erythropoietin resistance index [ERI = total weekly ESA dose (IU)/weight
      (kg)/haemoglobin concentration (g/dL] was used as a measure of ESA dose
      requirements. RESULTS: There was no difference in ERI between those with RRF as
      compared to those without (9.5 versus 11.0, respectively; P = 0.45). Also, ERI
      did not differ between those receiving haemodialysis as compared with peritoneal
      dialysis (10.8 versus 10.2, respectively; P = 0.84) or in those using renin
      angiotensin system (RAS) blockers as compared with no RAS blocker use (11.6
      versus 9.2, respectively; P = 0.10). Lower ERI was evident for those with cystic
      kidney disease as compared to those with other causes of ESKD (6.9 versus 16.5,
      respectively; P = 0.32) although this did not reach statistical significance.
      Higher ERI was found in those with evidence of systemic inflammation as compared
      to those without (16.5 versus 9.5, respectively; P = 0.003). CONCLUSIONS: There
      was no association between RRF and ESA dose requirements, irrespective of
      dialysis modality, RAS blocker use, primary renal disease or hyperparathyroidism.

PMID- 29178880
TI  - Evaluation of effects of Mycoplasma mastitis on milk composition in dairy cattle
      from South Australia.
AB  - BACKGROUND: Mycoplasma mastitis is increasingly posing significant impact on
      dairy industry. Although the effects of major conventional mastitis pathogens on
      milk components has been widely addressed in the literature, limited data on the
      effects of different Mycoplasma and Acholeplasma spp. on milk quality and
      quantity is available. The aim of this study was to determine the casual
      relationship of Mycoplasma spp. and A. laidlawii to mastitis and compare them to
      subclinical mastitis caused by conventional mastitis pathogens from a single
      dairy herd in South Australia; Mycoplasma spp. and A. laidlawii were detected
      using PCR applied directly to milk samples. The herd had mastitis problem with
      high somatic cell count and low response rate to conventional antimicrobial
      therapy. A total of 288 cow-level milk samples were collected aseptically and
      used in this study. RESULTS: Conventional culture showed a predominance of
      coagulase-negative staphylococci, followed by coagulase-positive staphylococci,
      Streptococcus spp., Enterococcus spp., E. coli, and Klebsiella spp. PCR results
      showed a high prevalence of mycoplasmas (76.7%), including A. laidlawii (10.8%),
      M. bovis (6.2%), M. bovirhinis (5.6%), M. arginini (2%), and (52.1%) of cows were
      co-infected with two or more Mycoplasma and Acholeplasma species. Mycoplasma co
      infection significantly increased somatic cell counts (SCC) similar to
      conventional mastitis pathogens and compared to non-infected cows with 389.3,
      550.3 and 67.3 respectively; and decreased the milk yield with 29.0, 29.9 and
      34.4 l, respectively. Mycoplasma co-infection caused significant increase in
      protein percentage, and significant decrease in fat percentage and total milk
      solids, similar to other conventional mastitis pathogens. In contrast, changes in
      milk composition and yield caused by various individual Mycoplasma species were
      non-significant. CONCLUSIONS: Mycoplasma mastitis had on-farm economic
      consequences similar to common conventional mastitis pathogens. Results of our
      study indicate that co-infection Mycoplasma mastitis caused similar effect on
      milk composition to other mastitis pathogens and we hope these findings raise the
      awareness of the importance of their detection on routine diagnostic panels.

PMID- 29178881
TI  - Atrial ERK1/2 activation in the embryo leads to incomplete Septal closure: a
      novel mouse model of atrial Septal defect.
AB  - BACKGROUND: MEK1 mutation and activated MAPK signaling has been found in patients
      with RASopathies and abnormal cardiac development. Previous studies have
      suggested that regulation of fetal MAPK signaling is essential for normal cardiac
      development. We investigated the effect of active MEK1 overexpression on fetal
      atrial septal development. METHODS AND RESULTS: An inducible double transgenic
      (DTg) mouse model was developed in which cardiac-specific fetal expression of a
      constitutively active form of human MEK1 (aMEK1) was induced primarily in the
      atrium via the withdrawal of doxycycline from the drinking water of pregnant
      mice. Atrial septal defect (ASD) was found in 51% (23/45) of DTg mice. Fifty-two
      percent (12/23) of ASD mice died before weaning, and surviving ASD mice exhibited
      hypertrophic hearts with enlarged right atria and decreased fractional shorting
      (40 +/- 2% vs. 48 +/- 0%, p < 0.05). The model mimicked human ASD in several key
      clinical features: severe ASD was associated with growth impairment; ASD-specific
      mortality was highest within the early postnatal period; despite an even
      distribution of ASD among the sexes, early mortality was significantly higher in
      males. The expression of aMEK1 and increased phosphorylation of ERK1/2 was
      documented via Western blot in DTg fetal hearts, with the largest increases seen
      in atrial tissue. In an alternative transgenic aMEK1 model with elevated atrial
      MKP3 expression and corresponding suppression of increases in ERK1/2
      phosphorylation, animals did not develop ASD. CONCLUSION: This new model of ASD
      suggests that enhanced atrial MEK1-ERK1/2 signaling during fetal development
      disrupts normal atrial septation, possibly regulated by the balance of ERK1/2
      phosphorylation.

PMID- 29178882
TI  - Characterization and susceptibility of streptococci and enterococci isolated from
      Nile tilapia (Oreochromis niloticus) showing septicaemia in aquaculture and wild
      sites in Egypt.
AB  - BACKGROUND: The present investigation was an endeavor into the elucidation of the
      disease-causing pathogen of streptococcosis in Nile tilapia (Oreochromis
      niloticus) in Egypt affecting adult fish cultured and wild fish in the Nile
      river. Fish were obtained from commercial fishermen, collected as part of their
      routine fishing activities. The researchers observed the routine fishing process
      and selected fish for use in the study, at the point of purchase from the
      fisherman. RESULTS: Diseased fish showed exophthalmia with accumulation of
      purulent and haemorrhagic fluid around eyes, and ventral petechial haemorrhages.
      The Post mortem examination revealed, abdominal fat haemorrhage, pericarditis and
      enlargement of the liver, spleen and kidney. Gram-stained smears revealed the
      presence of Gram-positive cocci, beta-hemolytic, oxidase and catalase negative.
      Analysis of the 16S rRNA gene confirmed that the 17 tilapia isolates studied were
      6/17 Enterococcus faecalis, 2/17 Enterococcus gallinarum, 3/17 Streptococcus
      pluranimalium, 2/17 Aerococcus viridans, 1/17 isolate of each Streptococcus
      dysgalactiae, Streptococcus anginosus, Lactococcus garvieae and Granulicetella
      elegans/Leuconostoc mesenteroides cremoris. It should be noted that there was no
      mixed infection. Multiple resistance was observed and the most frequent
      antibiotic combination was penicillin, ampicillin, vancomycin, chloramphenicol,
      rifampicin, ofloxacin, clindamycin, erythromycin and tetracycline representing
      eight classes. CONCLUSIONS: Consequently, we concluded that Streptococcus species
      are an emerging pathogen for Nile tilapia aquaculture in Egypt and to be
      considered as a new candidate in the warm water fish diseases in Egypt with
      special reference to L. garvieae, S. dysgalactiae in addition to L. mesenteroides
      cremoris which was not reported before from tilapia and taking into consideration
      their zoonotic implications for public health.

PMID- 29178883
TI  - Whole genome sequence and a phylogenetic analysis of the G8P[14] group A
      rotavirus strain from roe deer.
AB  - BACKGROUND: Group A rotaviruses (RVA) are associated with acute gastroenteritis
      in children and in young domestic and wild animals. A RVA strain was detected
      from a roe deer for the first time during a survey of game animals in Slovenia in
      2014. A further RVA strain (SLO/D110-15) was detected from a roe deer during
      2015. The aim of this study was to provide a full genetic profile of the detected
      RVA strain from roe deer and to obtain additional information about zoonotic
      transmitted strains and potential reassortments between human rotavirus strains
      and zoonotic transmitted rotavirus strains. The next generation sequencing (NGS)
      analysis on Ion Torrent was performed and the whole genome sequence has been
      determined together with a phylogenetic analysis. RESULTS: The whole genome
      sequence of SLO/D110-15 was obtained by NGS analyses on an IonTorrent platform.
      According to the genetic profile, the strain SLO/D110-15 clusters with the DS-1
      like group and expresses the G8-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3 genome
      constellation. Phylogenetic analysis shows that this roe deer G8P[14] strain is
      most closely related to RVA strains found in sheep, cattle and humans. A human
      RVA strain with the same genotype profile was detected in 2009 in Slovenia.
      CONCLUSIONS: The G8P[14] genotype has been found, for the first time, in deer, a
      newly described host from the order Artiodactyla for this RVA genotype. The
      finding of a rotavirus with the same genome segment constellation in humans
      indicates the possible zoonotic potential of this virus strain.

PMID- 29178884
TI  - A new panel of SNPs to assess thyroid carcinoma risk: a pilot study in a
      Brazilian admixture population.
AB  - BACKGROUND: Thyroid cancer is a common malignant disease of the endocrine system
      with increasing incidence rates over the last few decades. In this study, we
      sought to analyze the possible association of 45 single nucleotide polymorphisms
      (SNPs) with thyroid cancer in a population from Rio Grande do Norte, Brazil.
      METHODS: Based on histological analysis by a pathologist, 80 normal thyroid
      specimens of tissue adjacent to thyroid tumors were obtained from the biobank at
      the Laboratory of Pathology of Liga Norte Riograndense Contra o Cancer, Natal,
      RN. Patient samples were then genotyped using the MassARRAY platform (Sequenon,
      Inc) followed by statistical analysis employing the SNPassoc package in R
      program. The genotypic frequencies of all 45 SNPs obtained from the International
      HapMap Project database and based on data from the ancestral populations of
      European and African origin were used to compose the control study group.
      RESULTS: In our study, the following 9 SNPs showed significant differences in
      their frequency when comparing the study and control groups: rs3744962, rs258107,
      rs1461855, rs4075022, rs9943744, rs4075570, rs2356508, rs17485896, and rs2651339.
      Furthermore, the SNPs rs374492 C/T and rs258107 C/T were associated with a
      relative risk for thyroid carcinoma of 3.78 (p = 6.27 * 10e-5) and 2.91 (p = 8.27
      * 10e-5), respectively, after Bonferroni's correction for multiple comparisons.
      CONCLUSIONS: These nine polymorphisms could be potential biomarkers of
      predisposition to thyroid carcinoma in the population from Rio Grande do Norte.
      However, complementary studies including a control group with samples obtained
      from healthy subjects in Rio Grande do Norte state, should be conducted to
      confirm these results.

PMID- 29178885
TI  - Severe maternal outcomes and quality of care at district hospitals in Rwanda- a
      multicentre prospective case-control study.
AB  - BACKGROUND: Despite a significant decrease in maternal mortality in the last
      decade, Rwanda needs further progress in order to achieve Sustainable Development
      Goals (SDG)3 which addresses among others maternal mortality. Analysis of severe
      maternal outcomes (SMO) was performed to identify their characteristics, causes
      and contributory factors, using standard indicators for quality of care. METHODS:
      A prospective case-control study was conducted for which data were collected
      between November 2015 and April 2016 in four rural district hospitals. The
      occurrence of SMO with near miss incidence ratios was established, followed by an
      analysis of the characteristics, clinical outcomes, causes and contributory
      factors. RESULTS: The SMO incidence ratio was 38.4 per 1000 live births (95% CI
      33.4-43.4) and the maternal near-miss incidence ratio was 36 per 1000 live births
      (95% CI 31.1-40.9). The leading causes of SMO were postpartum haemorrhage
      (23.4%), uterine rupture (22.9%), abortion related complications (16.8%), malaria
      (13.6%) and hypertensive disorders (8.9%). The case fatality rate was high for
      women with hypertensive disorders (10.5%; CI 3.3-24.3) and severe postpartum
      haemorrhage (8%; CI 0.5-15.5). Stillbirth (OR = 181.7; CI 43.5-757.9) and length
      of stay at the hospital (OR = 7.9; CI 4.5-13.8) were strongly associated with
      severe outcomes. CONCLUSIONS: Despite the use of life saving interventions, SMO
      are frequent. Mortality index was found to be low at the level of district
      hospitals. SMO were associated with long stay at the hospital and stillbirth.
      There is a need for improvement of quality of care, referral practices and
      certain types of infrastructure, especially blood banks, which would ensure truly
      comprehensive emergency obstetric care and reduce the occurrence of SMO.

PMID- 29178886
TI  - Physical examination in undergraduate medical education in the field of general
      practice - a scoping review.
AB  - BACKGROUND: Physical examination (PE) is an essential clinical skill and a
      central part of a physician's daily activity. Teaching of PE has been integrated
      into medical school by many clinical disciplines with respective specific
      examination procedures. For instance, PE teaching in general practice may include
      a full-body examination approach. Studies show that PE-skills of medical students
      often need enhancement. The aim of this article was to scope the literature
      regarding the teaching and research of PE within general practice during
      undergraduate medical education. We evaluated a wide breadth of literature
      relating to the content, study design, country of research institution and year
      of publication. METHODS: Literature search in Medline along the PRISMA-P protocol
      was performed by search syntax ("physical examination" AND "medical education"
      AND "undergraduate" AND general practice) considering Medline MeSH (Medical
      Subject Heading)-Terms and Medline search term tree structure. Independent title,
      abstract and full-text screening with defined inclusion and exclusion criteria
      was performed. Full texts were analyzed by publication year, country of origin,
      study design and content (by categorizing articles along their main topic
      according to qualitative content analysis of Mayring). RESULTS: One-hundred seven
      articles were included. The annual number of publications ranged from 4 to 14 and
      had a slightly rising trend since 2000. Nearly half of the publications
      originated from the United States (n = 54), 33 from Canada and the United
      Kingdom. Overall, intervention studies represented the largest group (n = 60,
      including uncontrolled and controlled studies, randomized and non-randomized),
      followed by cross-sectional studies (n = 29). The 117 studies could be assigned
      to five categories "teaching methods (n = 53)", "teaching quality (n = 33)",
      "performance evaluation and examination formats (n=19)", "students' views (n =
      8)" and "patients' and standardized patients' views (n=4)". CONCLUSIONS: The
      present work shows a wide spectrum of teaching and research activities and a
      certain level of evidence for the effectiveness of individual teaching methods.
      It can be used as orientation and impulse generator for the further development
      of medical education in the field of PE.

PMID- 29178887
TI  - A multiscale modeling study of particle size effects on the tissue penetration
      efficacy of drug-delivery nanoparticles.
AB  - BACKGROUND: Particle size is a key parameter for drug-delivery nanoparticle
      design. It is believed that the size of a nanoparticle may have important effects
      on its ability to overcome the transport barriers in biological tissues.
      Nonetheless, such effects remain poorly understood. Using a multiscale model,
      this work investigates particle size effects on the tissue distribution and
      penetration efficacy of drug-delivery nanoparticles. RESULTS: We have developed a
      multiscale spatiotemporal model of nanoparticle transport in biological tissues.
      The model implements a time-adaptive Brownian Dynamics algorithm that links
      microscale particle-cell interactions and adhesion dynamics to tissue-scale
      particle dispersion and penetration. The model accounts for the advection,
      diffusion, and cellular uptakes of particles. Using the model, we have analyzed
      how particle size affects the intra-tissue dispersion and penetration of drug
      delivery nanoparticles. We focused on two published experimental works that
      investigated particle size effects in in vitro and in vivo tissue conditions. By
      analyzing experimental data reported in these two studies, we show that particle
      size effects may appear pronounced in an in vitro cell-free tissue system, such
      as collagen matrix. In an in vivo tissue system, the effects of particle size
      could be relatively modest. We provide a detailed analysis on how particle-cell
      interactions may determine distribution and penetration of nanoparticles in a
      biological tissue. CONCLUSION: Our work suggests that the size of a nanoparticle
      may play a less significant role in its ability to overcome the intra-tissue
      transport barriers. We show that experiments involving cell-free tissue systems
      may yield misleading observations of particle size effects due to the absence of
      advective transport and particle-cell interactions.

PMID- 29178888
TI  - Anaemia is an essential complication of ANCA-associated renal vasculitis: a
      single center cohort study.
AB  - BACKGROUND: Anaemia is a common complication of patients with antineutrophil
      cytoplasmic antibody (ANCA)-associated renal vasculitis. Nevertheless, the cause
      and degree of such cases of anaemia have not been elucidated in detail. We aimed
      to investigate the prevalence, cause, pathogenesis of anaemia and the impact of
      anaemia on prognosis in patients with ANCA-associated renal vasculitis. METHODS:
      We identified 45 patients with ANCA-associated renal vasculitis that were
      clinically and/or histologically diagnosed and treated from 2003 to 2014 at
      University of Tsukuba Hospital. The relationships between anaemia and various
      clinicopathological findings were evaluated. RESULTS: At the time of diagnosis of
      ANCA-associated renal vasculitis, all patients showed anaemia, with a mean
      haemoglobin level of 7.5 +/- 1.3 g/dL. Renal anaemia was diagnosed in 92% of
      patients, anaemia of chronic disease (ACD) in 56%, and anaemia due to hemorrhage
      in 20%. Next, the patients were divided into two groups according to anaemia
      severity: minimum haemoglobin (min Hb) < 7.5 (n = 24) and min Hb >= 7.5 (n = 21).
      A comparison of baseline characteristics showed that serum albumin, maximum serum
      creatinine, minimum estimated glomerular filtration rate (eGFR), serum cystatin
      C, and the area of tubulointerstitial damage were significantly different between
      the haemoglobin groups (p <  0.05). No significant intergroup differences were
      observed in iron-related or inflammation-related data. With regard to the
      relationship between anaemia severity and prognosis, patients in the min Hb < 7.5
      group tended to have a lower eGFR. Anaemia severity was associated with markedly
      lower survival (Log-rank test, p = 0.03). CONCLUSIONS: In this cohort of patients
      with ANCA-associated renal vasculitis, all subjects exhibited anaemia. In regard
      to the cause and pathogenesis, the most prevalent form of anaemia was renal
      anaemia, not ACD, and a potential reason for the high prevalence of anaemia in
      our cohort may have been the interaction between renal anaemia and ACD. Moreover,
      anaemia severity was significantly associated with the degree of renal
      dysfunction and life prognosis.

PMID- 29178889
TI  - Lookism hurts: appearance discrimination and self-rated health in South Korea.
AB  - BACKGROUND: Despite a growing body of evidence suggesting that discrimination
      harms health, the association between appearance discrimination and health has
      been understudied. Our study investigated the association between perceived
      appearance discrimination and self-rated health among emerging adults using a
      nationally representative cohort study in South Korea. METHODS: We analyzed the
      2nd-10th (2005-2013) waves of cohort data from the Korean Education Employment
      Panel (KEEP). KEEP consists of two groups of individuals who were 15 (group I)
      and 18 (group II) years old at the 1st wave of the survey (2004) and were
      followed annually. Appearance discrimination was assessed at baseline (19 years
      old: 5th wave for group I, 2nd wave for group II) and at follow-up (24 years old:
      10th wave for group I, 7th wave for group II). Responses of appearance
      discrimination at the two-time points were classified into four groups: 1) never
      (no discrimination at both baseline and follow-up); 2) repeated (discrimination
      at both baseline and follow-up); 3) incident (discrimination only at follow-up);
      and 4) in error (discrimination only at baseline). Multivariate logistic
      regression was applied to examine the association between reporting patterns of
      appearance discrimination and poor self-rated health, adjusting for potential
      confounders. RESULTS: Compared to those who did not experience appearance
      discrimination, 'repeated' (OR: 3.70; 95% CI: 2.19-6.27) and 'incident' (OR:
      3.10; 95% CI: 1.99-4.83) groups had a higher odds ratio of poor self-rated health
      after adjusting for potential confounders including respondents' body mass index
      change and baseline self-rated health. However, no significant association was
      observed among those who reported appearance discrimination 'in error'.
      CONCLUSIONS: These results suggest that perceived appearance discrimination is
      associated with the health of Korean emerging adults considering participants'
      reporting patterns of appearance discrimination.

PMID- 29178891
TI  - Rationale and design for SHAREHD: a quality improvement collaborative to scale up
      Shared Haemodialysis Care for patients on centre based haemodialysis.
AB  - BACKGROUND: The study objective is to assess the effectiveness and economic
      impact of a structured programme to support patient involvement in centre-based
      haemodialysis and to understand what works for whom in what circumstances and
      why. It implements a program of Shared Haemodialysis Care (SHC) that aims to
      improve experience and outcomes for those who are treated with centre-based
      haemodialysis, and give more patients the confidence to dialyse independently
      both at centres and at home. METHODS/DESIGN: The 24 month mixed methods cohort
      evaluation of 600 prevalent centre based HD patients is nested within a 30 month
      quality improvement program that aims to scale up SHC at 12 dialysis centres
      across England. SHC describes an intervention where patients who receive centre
      based haemodialysis are given the opportunity to learn, engage with and undertake
      tasks associated with their treatment. Following a 6-month set up period, a
      phased implementation programme is initiated across 12 dialysis units using a
      randomised stepped wedge design with 6 centres participating in each of 2 steps,
      each lasting 6 months. The intervention utilises quality improvement
      methodologies involving rapid tests of change to determine the most appropriate
      mechanisms for implementation in the context of a learning collaborative. Running
      parallel with the stepped wedge intervention is a mixed methods cohort evaluation
      that employs patient questionnaires and interviews, and will link with routinely
      collected data at the end of the study period. The primary outcome measure is the
      number of patients performing at least 5 dialysis-related tasks collected using 3
      monthly questionnaires. Secondary outcomes measures include: the number of people
      choosing to perform home haemodialysis or dialyse independently in-centre by the
      end of the study period; end-user recommendation; home dialysis establishment
      delay; staff impact and confidence; hospitalisation; infection and health
      economics. DISCUSSION: The results from this study will provide evidence of
      impact of SHC, barriers to patient and centre level adoption and inform
      development of future interventions to support its implementation. TRIAL
      REGISTRATION: ISRCTN Number: 93999549 , (retrospectively registered 1st May
      2017); NIHR Research Portfolio: 31566.

PMID- 29178890
TI  - Cytokine and autoantibody clusters interaction in systemic lupus erythematosus.
AB  - BACKGROUND: Evidence supports the existence of different subphenotypes in
      systemic lupus erythematosus (SLE) and the pivotal role of cytokines and
      autoantibodies, which interact in a highly complex network. Thus, understanding
      how these complex nonlinear processes are connected and observed in real-life
      settings is a major challenge. Cluster approaches may assist in the
      identification of these subphenotypes, which represent such a phenomenon, and may
      contribute to the development of personalized medicine. Therefore, the
      relationship between autoantibody and cytokine clusters in SLE was analyzed.
      METHODS: This was an exploratory study in which 67 consecutive women with
      established SLE were assessed. Clinical characteristics including disease
      activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were
      measured simultaneously. Mixed-cluster methodology and bivariate analyses were
      used to define autoantibody and cytokine clusters and to identify associations
      between them and related variables. RESULTS: First, three clusters of
      autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)
      dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels
      above the threshold thus making possible to find 4 clusters: (1) neutral, (2)
      chemotactic, (3) G-CSF dominant, and (4) IFNalpha/Pro-inflammatory. Furthermore,
      the disease activity was associated with cytokine clusters, which, in turn, were
      associated with autoantibody clusters. Finally, when all biomarkers were
      included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3)
      IFN/dsDNA, which were also associated with disease activity. CONCLUSION: These
      results support the existence of three SLE cytokine-autoantibody driven
      subphenotypes. They encourage the practice of personalized medicine, and support
      proof-of-concept studies.

PMID- 29178892
TI  - Knobloch syndrome associated with Polymicrogyria and early onset of retinal
      detachment: two case reports.
AB  - BACKGROUND: Knobloch Syndrome (KS) is a rare congenital syndrome characterized by
      occipital skull defects and vitreoretinal degeneration. Retinal detachment (RD)
      often occurs at the end of the first decade of life or later. Aside from
      occipital skull defects, central nervous system abnormalities are uncommon. CASE
      PRESENTATIONS: We report on two siblings with KS. The first, a seven month old
      male, presented with nystagmus and was found to have a serous RD and a
      tessellated retinal appearance. His sister had a history of multiple visual
      abnormalities and had a similar retinal appearance although no signs of RD, but
      retina staphylomas. Genetic testing performed on both siblings showed a mutation
      in COL18A1, diagnostic of KS. MRI of both siblings demonstrated polymicrogyria
      but did not show occipital defects. CONCLUSIONS: Although several families with
      KS have been described previously, our case is noteworthy for several reasons.
      The RD observed in our first patient occurred at an early age, and we find
      evidence of only one patient with KS who had an RD identified at an earlier age.
      The findings of polymicrogyria are not characteristic of KS, and we found only a
      few previous reports of this association. Additionally, we review potential
      treatment options for this condition.

PMID- 29178893
TI  - 3D whole-heart phase sensitive inversion recovery CMR for simultaneous black
      blood late gadolinium enhancement and bright-blood coronary CMR angiography.
AB  - BACKGROUND: Phase sensitive inversion recovery (PSIR) applied to late gadolinium
      enhancement (LGE) imaging is widely used in clinical practice. However,
      conventional 2D PSIR LGE sequences provide sub-optimal contrast between scar
      tissue and blood pool, rendering the detection of subendocardial infarcts and
      scar segmentation challenging. Furthermore, the acquisition of a low flip angle
      reference image doubles the acquisition time without providing any additional
      diagnostic information. The purpose of this study was to develop and test a novel
      3D whole-heart PSIR-like framework, named BOOST, enabling simultaneous black
      blood LGE assessment and bright-blood visualization of cardiac anatomy. METHODS:
      The proposed approach alternates the acquisition of a 3D volume preceded by a T2
      prepared Inversion Recovery (T2Prep-IR) module (magnitude image) with the
      acquisition of a T2-prepared 3D volume (reference image). The two volumes (T2Prep
      IR BOOST and bright-blood T2Prep BOOST) are combined in a PSIR-like
      reconstruction to obtain a complementary 3D black-blood volume for LGE assessment
      (PSIR BOOST). The black-blood PSIR BOOST and the bright-blood T2Prep BOOST
      datasets were compared to conventional clinical sequences for scar detection and
      coronary CMR angiography (CMRA) in 18 patients with a spectrum of cardiovascular
      disease (CVD). RESULTS: Datasets from 12 patients were quantitatively analysed.
      The black-blood PSIR BOOST dataset provided statistically improved contrast to
      noise ratio (CNR) between blood and scar when compared to a clinical 2D PSIR
      sequence (15.8 +/- 3.3 and 4.1 +/- 5.6, respectively). Overall agreement in LGE
      depiction was found between 3D black-blood PSIR BOOST and clinical 2D PSIR
      acquisitions, with 11/12 PSIR BOOST datasets considered diagnostic. The bright
      blood T2Prep BOOST dataset provided high quality depiction of the proximal
      coronary segments, with improvement of visual score when compared to a clinical
      CMRA sequence. Acquisition time of BOOST (~10 min), providing information on both
      LGE uptake and heart anatomy, was comparable to that of a clinical single CMRA
      sequence. CONCLUSIONS: The feasibility of BOOST for simultaneous black-blood LGE
      assessment and bright-blood coronary angiography was successfully tested in
      patients with cardiovascular disease. The framework enables free-breathing multi
      contrast whole-heart acquisitions with 100% scan efficiency and predictable scan
      time. Complementary information on 3D LGE and heart anatomy are obtained reducing
      examination time.

PMID- 29178894
TI  - Changes in overall ventricular myocardial architecture in the setting of a
      porcine animal model of right ventricular dilation.
AB  - BACKGROUND: Chronic pulmonary regurgitation often leads to myocardial dysfunction
      and heart failure. It is not fully known why secondary hypertrophy cannot fully
      protect against the increase in wall stress brought about by the increased end
      diastolic volume in ventricular dilation. It has been assumed that mural
      architecture is not deranged in this situation, but we hypothesised that there
      might be a change in the pattern of orientation of the aggregations of
      cardiomyocytes, which would contribute to contractile impairment. METHODS: We
      created pulmonary valvular regurgitation by open chest, surgical suturing of its
      leaflets in seven piglets, performing sham operations in seven control animals.
      Using cardiovascular magnetic resonance imaging after 12 weeks of recovery, we
      demonstrated significantly increased right ventricular volumes in the test group.
      After sacrifice, diffusion tensor imaging of their hearts permitted measurement
      of the orientation of the cardiomyocytes. RESULTS: The helical angles in the
      right ventricle approached a more circumferential orientation in the setting of
      right ventricular RV dilation (p = 0.007), with an increased proportion of
      surface-parallel cardiomyocytes. In contrast, this proportion decreased in the
      left ventricle. Also in the left ventricle a higher proportion of E3 angles with
      a value around zero was found, and conversely a lower proportion of angles was
      found with a numerical higher value. In the dilated right ventricle the
      proportion of E3 angles around -90 degrees  is increased, while the proportion
      around 90 degrees  is decreased. CONCLUSION: Contrary to traditional views, there
      is a change in the orientation of both the left ventricular and right ventricular
      cardiomyocytes subsequent to right ventricular dilation. This will change their
      direction of contraction and hinder the achievement of normalisation of
      cardiomyocytic strain, affecting overall contractility. We suggest that the
      aetiology of the cardiac failure induced by right vetricular dilation may be
      partly explained by morphological changes in the myocardium itself.

PMID- 29178895
TI  - Informed, advance refusals of treatment by people with severe mental illness in a
      randomised controlled trial of joint crisis plans: demand, content and
      correlates.
AB  - BACKGROUND: In the UK, crisis planning for mental health care should acknowledge
      the right to make an informed advance treatment refusal under the Mental Capacity
      Act 2005. Our aims were to estimate the demand for such treatment refusals within
      a sample of service users who had had a recent hospital admission for psychosis
      or bipolar disorder, and to examine the relationship between refusals, and
      service user characteristics. METHODS: To identify refusals we conducted content
      analysis of Joint Crisis Plans, which are plans formulated by service users and
      their clinical team with involvement from an external facilitator, and routine
      care plans in sub-samples from a multi-centre randomised controlled trial of
      Joint Crisis Plans (plus routine mental health care) versus routine care alone
      (CRIMSON) in England. Factors hypothesised to be associated with refusals were
      identified using the trial data collected through baseline interviews of service
      users and clinicians and collection of routine clinical data. RESULTS: Ninety
      nine of 221 (45%) of the Joint Crisis Plans contained a treatment refusal
      compared to 10 of 424 (2.4%) baseline routine care plans. No Joint Crisis Plans
      recorded disagreement with refusals on the part of clinicians. Among those with
      completed Joint Crisis Plans, adjusted analyses indicated a significant
      association between treatment refusals and perceived coercion at baseline (odds
      ratio = 1.21, 95% CI 1.02-1.43), but not with baseline working alliance or a past
      history of involuntary admission. CONCLUSIONS: We demonstrated significant demand
      for written treatment refusals in line with the Mental Capacity Act 2005, which
      had not previously been elicited by the process of treatment planning. Future
      treatment/crisis plans should incorporate the opportunity for service users to
      record a treatment refusal during the drafting of such plans. TRIAL REGISTRATION:
      ISRCTN11501328 Registered 13th March 2008.

PMID- 29178896
TI  - Estimating the value of point-of-care HPV testing in three low- and middle-income
      countries: a modeling study.
AB  - BACKGROUND: Where resources are available, the World Health Organization
      recommends cervical cancer screening with human papillomavirus (HPV) DNA testing
      and subsequent treatment of HPV-positive women with timely cryotherapy. Newer
      technologies may facilitate a same-day screen-and-treat approach, but these
      testing systems are generally too expensive for widespread use in low-resource
      settings. METHODS: To assess the value of a hypothetical point-of-care HPV test,
      we used a mathematical simulation model of the natural history of HPV and data
      from the START-UP multi-site demonstration project to estimate the health
      benefits and costs associated with a shift from a 2-visit approach (requiring a
      return visit for treatment) to 1-visit HPV testing (i.e., screen-and-treat). We
      estimated the incremental net monetary benefit (INMB), which represents the
      maximum additional lifetime cost per woman that could be incurred for a new point
      of-care HPV test to be cost-effective, depending on expected loss to follow-up
      between visits (LTFU) in a given setting. RESULTS: For screening three times in a
      lifetime at 100% coverage of the target population, when LTFU was 10%, the INMB
      of the 1-visit relative to the 2-visit approach was I$13 in India, I$36 in
      Nicaragua, and I$17 in Uganda. If LTFU was 30% or greater, the INMB values for
      the 1-visit approach in all countries was equivalent to or exceeded total
      lifetime costs associated with screening three times in a lifetime. At a LTFU
      level of 70%, the INMB of the 1-visit approach was I$127 in India, I$399 in
      Nicaragua, and I$121 in Uganda. CONCLUSIONS: These findings indicate that point
      of-care technology for cervical cancer screening may be worthy of high investment
      if linkage to treatment can be assured, particularly in settings where LTFU is
      high.

PMID- 29178897
TI  - MicroRNA expression changes in association with changes in interleukin
      1beta/interleukin10 ratios produced by monocytes in autism spectrum disorders:
      their association with neuropsychiatric symptoms and comorbid conditions
      (observational study).
AB  - BACKGROUND: MicroRNAs (miRNAs) play a major role in regulating immune responses
      at post-transcriptional levels. Previously, we have reported fluctuating
      interlukine-1beta (IL-1beta)/IL-10 ratios produced by peripheral blood monocytes
      (PBMo) in some patients with autism spectrum disorders (ASD). This study examined
      whether changes in miRNA expression by PBMo are associated with changes in IL
      1beta/IL-10 ratios and how such changes are associated with ASD clinical
      features. METHODS: miRNA expression by purified PBMo from ASD subjects (N = 69)
      and non-ASD controls (N = 27) were determined by high-throughput sequencing.
      Cytokine production by PBMo in responses to stimuli of innate immunity, and
      behavioral symptoms [assessed by aberrant behavioral checklist (ABC)] were also
      evaluated at the same time of sample obtainment. RESULTS: As a whole, there was
      no difference in miRNA expression between ASD and control non-ASD PBMo. However,
      when ASD cells were subdivided into 3 groups with high, normal, or low IL
      1beta/IL-10 ratios as defined in the "Results" section, in comparison with the
      data obtained from non-ASD controls, we observed marked changes in miRNA
      expression. Namely, over 3-fold changes in expression of miR-181a, miR-93, miR
      223, miR-342, and miR-1248 were observed in ASD PBMo with high or low IL-1beta/IL
      10 ratios, but not in ASD PBMo with normal ratios. These miRNAs that had altered
      in expression are those closely associated with the regulation of key signaling
      pathways. With changes in IL-1beta/IL-10 ratios, we also observed changes in the
      production of cytokines (IL-6, TNF-alpha, and TGF-beta) other than IL-1beta/IL-10
      by ASD PBMo. The association between behavioral symptoms and cytokine levels was
      different when ASD cells exhibit high/low IL-1beta/IL-10 ratios vs. when ASD
      cells exhibited normal ratios. Non-IgE-mediated food allergy was also observed at
      higher frequency in ASD subjects with high/low IL-1beta/IL-10 ratios than with
      normal ratios. CONCLUSIONS: Changes in cytokine profiles and miRNA expression by
      PBMo appear to be associated with changes in ASD behavioral symptoms. miRNAs that
      are altered in expression in ASD PBMo with high/low IL-1beta/IL-10 ratios are
      those associated with inflammatory responses. Changes in IL-1beta/IL-10 ratios
      along with changes in miRNA expression may serve as biomarkers for immune
      mediated inflammation in ASD.

PMID- 29178898
TI  - The wearable cardioverter defibrillator as a bridge to reimplantation in patients
      with ICD or CRT-D-related infections.
AB  - BACKGROUND: The approach to treat device infection in patients with implantable
      cardioverter defibrillator (ICD) or cardiac resynchronization therapy
      defibrillator (CRT-D) is a challenging procedure. Optimal treatment is complete
      extraction of the infected device. To protect these patients from sudden cardiac
      arrest while waiting for reimplantation and to avoid recurrent infection, a
      wearable cardioverter defibrillator (WCD) seems to be a valuable solution.
      Therefore, we investigated the management and outcome of patients with ICD or CRT
      D infections using the WCD as a bridge to re-implantation after lead extraction
      procedures. METHODS: We conducted a retrospective study on consecutive patients
      who underwent ICD or CRT-D removal due to device-related local or systemic
      infections. All patients were prescribed a WCD at our center between 01/2012 and
      10/2015. All patients returned to our outpatient clinic for regular ICD or CRT-D
      monitoring initially 1 and 3 months after reimplantation followed by 6-months
      intervals. RESULTS: Twenty-one patients (mean age 65.0 +/- 8.0 years, male 76.2%)
      were included in the study. Complete lead extraction was achieved in all
      patients. While waiting for reimplantation one patient experienced a symptomatic
      episode of sustained ventricular tachycardia. This episode was converted
      successfully into sinus rhythm by a single 150 J shock. Mean follow-up time 392
      +/- 206 days, showing survival rate of 100% and freedom from reinfection in all
      patients. CONCLUSION: The WCD seems to be a valuable bridging option for patients
      with ICD or CRT-D infections, showing no recurrent device infection.

PMID- 29178899
TI  - Smoking and alcohol cessation intervention in relation to radical cystectomy: a
      qualitative study of cancer patients' experiences.
AB  - BACKGROUND: Despite smoking and risky alcohol drinking being modifiable risk
      factors for cancer as well as postoperative complications, perioperative
      cessation counselling is often ignored. Little is known about how cancer patients
      experience smoking and alcohol interventions in relation to surgery. Therefore
      the aim of this study was to explore how bladder cancer patients experience a
      perioperative smoking and alcohol cessation intervention in relation to radical
      cystectomy. METHODS: A qualitative study was conducted in two urology out-patient
      clinics. We conducted semi-structured in-depth interviews with 11 purposively
      sampled persons who had received the smoking and alcohol cessation intervention.
      The analysis followed the steps contained in the thematic network analysis.
      RESULTS: Two global themes emerged: "smoking and alcohol cessation was
      experienced as an integral part of bladder cancer surgery" and "returning to
      everyday life was a barrier for continued smoking cessation/alcohol reduction".
      Participants described that during hospitalization their focus shifted to the
      operation and they did not experience craving to smoke or drink alcohol.
      Concurrent with improved well-being or experiencing stressful situations, the
      risk of relapse increased when returning to everyday life. CONCLUSIONS: The
      smoking and alcohol cessation intervention was well received by the participants.
      Cancer surgery served as a kind of refuge and was a useful cue for motivating
      patients to quit smoking and to reconsider the consequences of risky drinking.
      These results adds to the sparse evidence of what supports smoking and alcohol
      cessation in relation to bladder cancer patients undergoing major surgery and
      point to the need to educate healthcare professionals in offering smoking and
      alcohol cessation interventions in hospitals. The study also provides knowledge
      about the intervention in the STOP-OP study and will help guide the design of
      future smoking and alcohol cessation studies aimed at cancer patients undergoing
      surgery.

PMID- 29178900
TI  - Social-cognitive determinants of the tick check: a cross-sectional study on self
      protective behavior in combatting Lyme disease.
AB  - BACKGROUND: Performing a tick check after visiting nature is considered the most
      important preventive measure to avoid contracting Lyme disease. Checking the body
      for ticks after visiting nature is the only measure that can fully guarantee
      whether one has been bitten by a tick and provides the opportunity to remove the
      tick as soon as possible, thereby greatly reducing the chance of contracting Lyme
      disease. However, compliance to performing the tick check is low. In addition,
      most previous studies on determinants of preventive measures to avoid Lyme
      disease lack a clear definition and/or operationalization of the term "preventive
      measures". Those that do distinguish multiple behaviors including the tick check,
      fail to describe the systematic steps that should be followed in order to perform
      the tick check effectively. Hence, the purpose of this study was to identify
      determinants of systematically performing the tick check, based on social
      cognitive theory. METHODS: A cross-sectional self-administered survey
      questionnaire was filled out online by 508 respondents (Mage = 51.7, SD = 16.0;
      50.2% men; 86.4% daily or weekly nature visitors). Bivariate correlations and
      multivariate regression analyses were conducted to identify associations between
      socio-cognitive determinants (i.e. concepts related to humans' intrinsic and
      extrinsic motivation to perform certain behavior), and the tick check, and
      between socio-cognitive determinants and proximal goal to do the tick check.
      RESULTS: The full regression model explained 28% of the variance in doing the
      tick check. Results showed that performing the tick check was associated with
      proximal goal (beta = .23, p < 0.01), self-efficacy (beta = .22, p < 0.01), self
      evaluative outcome expectations (beta = .21, p < 0.01), descriptive norm (beta =
      .16, p < 0.01), and experience (beta = .13, p < 0.01). CONCLUSIONS: Our study is
      among the first to examine the determinants of systematic performance of the tick
      check, using an extended version of social cognitive theory to identify
      determinants. Based on the results, a number of practical recommendations can be
      made to promote the performance of the tick check.

PMID- 29178901
TI  - Bereaved family members' perceptions of the quality of end-of-life care across
      four types of inpatient care settings.
AB  - BACKGROUND: The aims of this study were to gain a better understanding of how
      bereaved family members perceive the quality of EOL care by comparing their
      satisfaction with quality of end-of-life care across four different settings and
      by additionally examining the extent to which demographic characteristics and
      psychological variables (resilience, optimism, grief) explain variation in
      satisfaction. METHODS: A cross-sectional mail-out survey was conducted of
      bereaved family members of patients who had died in extended care units (n = 63),
      intensive care units (n = 30), medical care units (n = 140) and palliative care
      units (n = 155). 1254 death records were screened and 712 bereaved family
      caregivers were identified as eligible, of which 558 (who were initially
      contacted by mail and then followed up by phone) agreed to receive a
      questionnaire and 388 returned a completed questionnaire (response rate of 70%).
      Measures included satisfaction with end-of-life care (CANHELP- Canadian Health
      Care Evaluation Project - family caregiver bereavement version; scores range from
      0 = not at all satisfied to 5 = completely satisfied), grief (Texas Revised
      Inventory of Grief (TRIG)), optimism (Life Orientation Test - Revised) and
      resilience (The Resilience Scale). ANCOVA and multivariate linear regression were
      used to analyze the data. RESULTS: Family members experienced significantly lower
      satisfaction in MCU (mean = 3.69) relative to other settings (means of 3.90
      [MCU], 4.14 [ICU], and 4.00 [PCU]; F (3371) = 8.30, p = .000). Statistically
      significant differences were also observed for CANHELP subscales of "doctor and
      nurse care", "illness management", "health services" and "communication". The
      regression model explained 18.9% of the variance in the CANHELP total scale, and
      between 11.8% and 27.8% of the variance in the subscales. Explained variance in
      the CANHELP total score was attributable to the setting of care and psychological
      characteristics of family members (44%), in particular resilience. CONCLUSION:
      Findings suggest room for improvement across all settings of care, but improving
      quality in acute care and palliative care should be a priority. Resiliency
      appears to be an important psychological characteristic in influencing how family
      members appraise care quality and point to possible sites for targeted
      intervention.

PMID- 29178902
TI  - Distinct association between educational attainment and overweight/obesity in
      unmarried and married women: evidence from a population-based study in Japan.
AB  - BACKGROUND: Associations between education and obesity have been consistently
      reported among women in developed countries, but few studies have considered the
      influence of marital status and husbands' education. This study aimed to examine
      differences in the association between education and overweight/obesity by
      marital status and to determine the contribution of husbands' education to
      overweight/obesity among community-dwelling Japanese women. METHODS: A
      questionnaire survey was conducted from 2010 to 2011 among residents aged 25-50
      years in Japanese metropolitan areas. Of 2145 women who agreed to participate and
      completed the survey, 582 were unmarried and 1563 were married.
      Overweight/obesity was defined as body mass index >=25 kg/m2. Multiple logistic
      regression analysis was conducted to determine whether women's or their husbands'
      education was associated with overweight/obesity after adjusting for age, work
      status, and equivalent income. RESULTS: The prevalence of overweight/obesity was
      11.9% among unmarried women and 10.3% among married women. Women's own education
      was significantly associated with overweight/obesity among unmarried women but
      not among married women. The multivariate-adjusted odds ratio of high school
      education or lower compared with university education or higher was 3.21 (95%
      confidence interval: 1.59-6.51) among unmarried women. Among married women,
      husbands' education was significantly associated with overweight/obesity: women
      whose husbands' educational attainment was high school or lower had significantly
      higher odds of overweight/obesity than did those whose husbands had a university
      education or higher (1.67, 95% confidence interval: 1.10-2.55). Among married
      women whose educational attainment was college or higher, women whose husbands'
      educational attainment was high school or lower had a significantly higher risk
      for overweight/obesity when compared with women whose husbands' educational
      attainment was college or higher. CONCLUSIONS: Associations between women's own
      education and overweight/obesity varied by marital status, and husbands'
      educational level was important for married women's overweight/obesity. These
      findings indicate that the social influences bound to educational background
      affect women's overweight/obesity.

PMID- 29178903
TI  - Development and in vivo validation of tissue-engineered, small-diameter vascular
      grafts from decellularized aortae of fetal pigs and canine vascular endothelial
      cells.
AB  - BACKGROUND: Tissue engineering has emerged as a promising alternative for small
      diameter vascular grafts. The aim of this study was to determine the feasibility
      of using decellularized aortae of fetal pigs (DAFPs) to construct tissue
      engineered, small-diameter vascular grafts and to test the performance and
      application of DAFPs as vascular tissue-engineered scaffolds in the canine
      arterial system. METHODS: DAFPs were prepared by continuous enzymatic digestion.
      Canine vascular endothelial cells (ECs) were seeded onto DAFPs in vitro and then
      the vascular grafts were cultured in a custom-designed vascular bioreactor system
      for 7 days of dynamic culture following 3 days of static culture. The grafts were
      then transplanted into the common carotid artery of the same seven dogs from
      which ECs had been derived (two grafts were prepared for each dog with one as a
      backup; therefore, a total of 14 tissue-engineered blood vessels were prepared).
      At 1, 3, and 6 months post-transplantation, ultrasonography and contrast-enhanced
      computed tomography (CT) were used to check the patency of the grafts.
      Additionally, vascular grafts were sampled for histological and electron
      microscopic examination. RESULTS: Tissue-engineered, small-diameter vascular
      grafts can be successfully constructed using DAFPs and canine vascular ECs.
      Ultrasonographic and CT test results confirmed that implanted vascular grafts
      displayed good patency with no obvious thrombi. Six months after implantation,
      the grafts had been remodeled and exhibited a similar structure to normal
      arteries. Immunohistochemical staining showed that cells had evenly infiltrated
      the tunica media and were identified as muscular fibroblasts. Scanning electron
      microscopy showed that the graft possessed a complete cell layer, and the
      internal cells of the graft were confirmed to be ECs by transmission electron
      microscopy. CONCLUSIONS: Tissue-engineered, small-diameter vascular grafts
      constructed using DAFPs and canine vascular ECs can be successfully transplanted
      to replace the canine common carotid artery. This investigation potentially paves
      the way for solving a problem of considerable clinical need, i.e., the
      requirement for small-diameter vascular grafts.

PMID- 29178904
TI  - Nutritional supplements and herbal medicines for women with polycystic ovary
      syndrome; a systematic review and meta-analysis.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common, reproductive
      endocrinopathy associated with serious short and long term health risks. Many
      women with PCOS use ingestible complementary medicines. This systematic review
      examined the effect on menstrual regulation and adverse effects from randomised
      controlled trials. METHODS: Randomised controlled trials (RCTs) that compared
      herbal or nutritional supplements to placebo or active controls in women with
      PCOS were eligible for inclusion. Electronic databases were searched to July
      2017. Study selection and assessment of quality were conducted independently by
      two review authors. RESULTS: Twenty four studies (1406 women) investigating seven
      nutritional supplements and four herbal medicines were included. No one study was
      assessed as having a low risk of bias. Four trials reported on the primary
      endpoint menstrual regulation. There was no evidence on improved menstrual
      regularity for calcium plus vitamin D compared to Metformin (RR: 0.66, 95% CI
      0.35 to 1.23, p = 0.19), reduced amenorrhoea for Camellia sinensis compared to
      placebo (RR: 0.17, 95% CI 0.02 to 1.72, p = 0.13) and no difference in the number
      of menses per month for Cinnamomum sp. against placebo (MD 0.05, 95% CI -0.36 to
      1.36, p = 0.26). Adverse effects were investigated in seven studies (164 women).
      Mild adverse effects were found for Cinnamomum sp. compared to placebo (17 women,
      RR: 0.36, 95% CI 0.03 to 0.70, p = 0.03). No difference was found for adverse
      effects between inositol, B complex vitamins, vitamin D, chromium and placebo.
      Improved reproduction, metabolic hormones and hyperandrogenism was found for
      inositol and improved cholesterol for omega three fish oils. CONCLUSION: There is
      no high quality evidence to support the effectiveness of nutritional supplements
      and herbal medicine for women with PCOS and evidence of safety is lacking. High
      quality trials of nutritional supplements and herbal medicines examining
      menstrual regulation and adverse effects in women with PCOS are needed.

PMID- 29178905
TI  - Diagnostic performance of semi-quantitative and quantitative stress CMR perfusion
      analysis: a meta-analysis.
AB  - BACKGROUND: Stress cardiovascular magnetic resonance (CMR) perfusion imaging is a
      promising modality for the evaluation of coronary artery disease (CAD) due to
      high spatial resolution and absence of radiation. Semi-quantitative and
      quantitative analysis of CMR perfusion are based on signal-intensity curves
      produced during the first-pass of gadolinium contrast. Multiple semi-quantitative
      and quantitative parameters have been introduced. Diagnostic performance of these
      parameters varies extensively among studies and standardized protocols are
      lacking. This study aims to determine the diagnostic accuracy of semi-
      quantitative and quantitative CMR perfusion parameters, compared to multiple
      reference standards. METHOD: Pubmed, WebOfScience, and Embase were systematically
      searched using predefined criteria (3272 articles). A check for duplicates was
      performed (1967 articles). Eligibility and relevance of the articles was
      determined by two reviewers using pre-defined criteria. The primary data
      extraction was performed independently by two researchers with the use of a
      predefined template. Differences in extracted data were resolved by discussion
      between the two researchers. The quality of the included studies was assessed
      using the 'Quality Assessment of Diagnostic Accuracy Studies Tool' (QUADAS-2).
      True positives, false positives, true negatives, and false negatives were
      subtracted/calculated from the articles. The principal summary measures used to
      assess diagnostic accuracy were sensitivity, specificity, andarea under the
      receiver operating curve (AUC). Data was pooled according to analysis territory,
      reference standard and perfusion parameter. RESULTS: Twenty-two articles were
      eligible based on the predefined study eligibility criteria. The pooled
      diagnostic accuracy for segment-, territory- and patient-based analyses showed
      good diagnostic performance with sensitivity of 0.88, 0.82, and 0.83, specificity
      of 0.72, 0.83, and 0.76 and AUC of 0.90, 0.84, and 0.87, respectively. In per
      territory analysis our results show similar diagnostic accuracy comparing
      anatomical (AUC 0.86(0.83-0.89)) and functional reference standards (AUC
      0.88(0.84-0.90)). Only the per territory analysis sensitivity did not show
      significant heterogeneity. None of the groups showed signs of publication bias.
      CONCLUSIONS: The clinical value of semi-quantitative and quantitative CMR
      perfusion analysis remains uncertain due to extensive inter-study heterogeneity
      and large differences in CMR perfusion acquisition protocols, reference
      standards, and methods of assessment of myocardial perfusion parameters. For wide
      spread implementation, standardization of CMR perfusion techniques is essential.
      TRIAL REGISTRATION: CRD42016040176 .

PMID- 29178906
TI  - Femoral nonunion with segmental bone defect treated by distraction osteogenesis
      with monolateral external fixation.
AB  - BACKGROUND: Currently, the common treatment for femoral nonunion with large
      segmental bone defect is difficult and complex. The effective surgical methods
      are rare, include vascularized bone grafting, Masquelet technique and Ilizarov
      distraction osteogenesis. The objective of this study is to investigate the
      outcomes of segmental femoral defects treated with monolateral external fixation
      using the distraction osteogenesis. METHODS: We retrospectively analyzed patients
      with femoral nonunion with segmental bone defects (> 6 cm) between January 2010
      and January 2014 in our single trauma center. All patients were treated by
      distraction osteogenesis with monolateral external fixation. All surgeries were
      performed by the same surgeon. Bone union, duration of distraction osteogenesis
      in days, time to consolidation in months, external fixation index (EFI),
      complications, and additional surgical interventions were recorded
      postoperatively. The modified Application of Methods of Illizarov (ASAMI)
      criteria were used to evaluate the operative effectiveness. RESULTS: Forty-one
      patients were enrolled in this study for analysis. The length of the bone defect
      ranged from 6 to 17 cm. All patients eventually achieved healing, and no patient
      experienced recurrence of infection or newly developed infection. The average
      time needed for healing was 13 months. In terms of the incidence of
      complications, 3 cases axial deviations, 5 cases docking site nonunion, 23 cases
      pin-tract infection, 14 cases knee joint stiffness or their joint mobility
      declined, 2 cases osteogenesis insufficient in the distraction area,1 case
      refracture, and 2 cases loose external fixation pins. In terms of the evaluations
      of fracture healing and function, 30 patients excellent, 6 patients good, 5
      patients fair, and 0 patient poor. In terms of postoperative function
      evaluations, 21 patients excellent, 9 patients good, 7 patients fair, and 4
      patients poor. CONCLUSION: For patients with femoral nonunion with large
      segmental bone defects, the monolateral external fixation can provide effective
      stability, improve compliance, and reduce complications.

PMID- 29178907
TI  - Impact of adenotonsillectomy on pediatric quality of life: review of the
      literature.
AB  - Adenotonsillectomy (ADT) is one of the most widely used procedures in the
      treatment of paediatric recurrent acute tonsillitis (RAT) and obstructive sleep
      apnoea syndrome (OSAS), both of which have significant repercussions on the
      patients' quality of life (QoL). The purpose of our review of literature was to
      highlight the great variety of tools that are currently used to evaluate QoL in
      children, to examine data available on their efficacy and the feasibility of
      their use in daily clinical practice, and to determine possible limitations
      related to an indirect and subjective assessment of QoL in children.Although the
      use of different parameters makes it difficult to compare the published studies,
      an analysis of the evidence currently available in the literature suggests that
      ADT has a generally positive impact on the QoL (especially in case of OSAS). It
      also highlights the importance of combining tonsillectomy and adenoidectomy in
      the treatment of OSAS, and documents the comparability of tonsillectomy and
      tonsillotomy in improving obstructive symptoms. In conclusion, our findings
      suggest that literature supports that ADT is associated with positive changes in
      QOL; however further studies using comparable standardised criteria are necessary
      to confirm the size and duration of this benefit.

PMID- 29178909
TI  - Functional diversity of home gardens and their agrobiodiversity conservation
      benefits in Benin, West Africa.
AB  - BACKGROUND: Understanding the functional diversity of home gardens and their
      socio-ecological determinants is essential for mainstreaming these agroforestry
      practices into agrobiodiversity conservation strategies. This paper analyzed
      functional diversity of home gardens, identified the socio-ecological drivers of
      functions assigned to them, and assessed the agrobiodiversity benefits of home
      gardens functions. METHODS: Using data on occurring species in home garden (HG)
      and functions assigned to each species by the gardeners, the study combined
      clustering and discriminant canonical analyses to explore the functional
      diversity of 360 home gardens in Benin, West Africa. Next, multinomial logistic
      models and chi-square tests were used to analyze the effect of socio-demographic
      characteristics of gardeners (age, gender, and education level), agro-ecological
      zones (humid, sub-humid, and semi-arid), and management regime (single and
      multiple managers) on the possession of a functional type of home gardens.
      Generalized linear models were used to assess the effect of the functions of home
      gardens and the determinant factor on their potential in conserving
      agrobiodiversity. RESULTS: Seven functional groups of home gardens, four with
      specific functions (food, medicinal, or both food and medicinal) and three with
      multiple functions (more than two main functions), were found. Women owned most
      of home gardens with primarily food plant production purpose while men owned most
      of home gardens with primarily medicinal plant production purposes. Finding also
      showed that multifunctional home gardens had higher plant species diversity.
      Specifically, crops and crop wild relatives occurred mainly in home gardens with
      food function while wild plant species were mostly found in home gardens with
      mainly medicinal function. CONCLUSIONS: Home gardening is driven by functions
      beyond food production. These functions are mostly related to direct and
      extractive values of home gardens. Functions of home gardens were gendered, with
      women mostly involved in home food gardens, and contribute to maintenance of
      crops and crop wild relatives while men were mostly home medicinal gardeners and
      contribute to the maintenance of wild plant species in home gardens. Although
      multiple functional home gardens were related to higher plant diversity, there
      was no guarantee for long-term maintenance of plant species in home gardens.

PMID- 29178908
TI  - Tick-borne pathogens in ticks collected from birds in Taiwan.
AB  - BACKGROUND: A variety of human diseases transmitted by arthropod vectors,
      including ticks, are emerging around the globe. Birds are known to be hosts of
      ticks and can disperse exotic ticks and tick-borne pathogens. In Taiwan, previous
      studies have focused predominantly on mammals, leaving the role of birds in the
      maintenance of ticks and dissemination of tick-borne pathogens undetermined.
      METHODS: Ticks were collected opportunistically when birds were studied from 1995
      to 2013. Furthermore, to improve knowledge on the prevalence and mean load of
      tick infestation on birds in Taiwan, ticks were thoroughly searched for when
      birds were mist-netted at seven sites between September 2014 and April 2016 in
      eastern Taiwan. Ticks were identified based on both morphological and molecular
      information and were screened for potential tick-borne pathogens, including the
      genera Anaplasma, Babesia, Borrelia, Ehrlichia and Rickettsia. Finally, a list of
      hard tick species collected from birds in Taiwan was compiled based on past work
      and the current study. RESULTS: Nineteen ticks (all larvae) were recovered from
      four of the 3096 unique mist-netted bird individuals, yielding a mean load of
      0.006 ticks/individual and an overall prevalence of 0.13%. A total of 139 ticks
      from birds, comprising 48 larvae, 35 nymphs, 55 adults and one individual of
      unknown life stage, were collected from 1995 to 2016, and 11 species of four
      genera were identified, including three newly recorded species (Haemaphysalis
      wellingtoni, Ixodes columnae and Ixodes turdus). A total of eight tick-borne
      pathogens were detected, with five species (Borrelia turdi, Anaplasma sp. clone
      BJ01, Ehrlichia sp. BL157-9, Rickettsia helvetica and Rickettsia monacensis) not
      previously isolated in Taiwan. Overall, 16 tick species of five genera have been
      recorded feeding on birds, including nine species first discovered in this study.
      CONCLUSION: Our study demonstrates the paucity of information on ticks of birds
      and emphasizes the need for more research on ticks of birds in Taiwan and
      Southeast Asia. Moreover, some newly recorded ticks and tick-borne pathogens were
      found only on migratory birds, demonstrating the necessity of further
      surveillance on these highly mobile species.

PMID- 29178910
TI  - Effects of dietary supplementation of leaves and whole plant of Andrographis
      paniculata on rumen fermentation, fatty acid composition and microbiota in goats.
AB  - BACKGROUND: The nature and amount of dietary medicinal plants are known to
      influence rumen fermentation and nutrient digestibility in ruminants.
      Nonetheless, changes in nutrient digestibility and rumen metabolism in response
      to dietary Andrographis paniculata (AP) in goats are unknown. This study examined
      the effects of dietary supplementation of leaves and whole plant of AP on
      nutrient digestibility, rumen fermentation, fatty acids and rumen microbial
      population in goats. Twenty-four Boer crossbred bucks (4 months old; average body
      weight of 20.18 +/- 0.19 kg) were randomly assigned to three dietary groups of
      eight goats each. The dietary treatments included a control diet (Basal diet
      without additive), basal diet +1.5% (w/w) Andrographis paniculata leaf powder
      (APL) and basal diet +1.5% (w/w) Andrographis paniculata whole plant powder
      (APW). The trial lasted 100 d following 14 d of adjustment. RESULTS: The rumen pH
      and concentration of propionate were greater (P < 0.05) in goats fed the APL and
      APW diets than those fed the control diet. The concentrations of ammonia nitrogen
      and acetate were greater (P < 0.05) in the control goats than the APL and APW
      goats. The digestibilities of crude protein, dry matter, acid detergent fibre and
      neutral detergent fibre were greater (P < 0.05) in the APL and APW goats compared
      to the control goats. Dietary APL and APW decreased (P < 0.05) the ruminal
      concentration of C18:0 and increased (P < 0.05) the ruminal concentration of
      C18:2n-6 and C18:3n-3. The APL goats had greater (P < 0.05) ruminal concentration
      of C18:1 trans-11 and CLA cis-9 trans-11 than the APW and control goats. Dietary
      treatments had no significant effect on the population of protozoa and
      methanogens in the rumen of goats. The ruminal populations of Ruminococcus albus,
      Ruminococcus flavefaciens and Fibrobacter succinogenes were greater (P < 0.05) in
      the APL and APW goats than the control goats. CONCLUSION: Dietary supplementation
      of leaves and whole plant of Andrographis paniculata can be used to manipulate
      rumen metabolism for improved nutrient digestibility in goats.

PMID- 29178912
TI  - Optimization of the prescription isodose line for Gamma Knife radiosurgery using
      the shot within shot technique.
AB  - BACKGROUND: This work explores how the choice of prescription isodose line (IDL)
      affects the dose gradient, target coverage, and treatment time for Gamma Knife
      radiosurgery when a smaller shot is encompassed within a larger shot at the same
      stereotactic coordinates (shot within shot technique). METHODS: Beam profiles for
      the 4, 8, and 16 mm collimator settings were extracted from the treatment
      planning system and characterized using Gaussian fits. The characterized data
      were used to create over 10,000 shot within shot configurations by systematically
      changing collimator weighting and choice of prescription IDL. Each configuration
      was quantified in terms of the dose gradient, target coverage, and beam-on time.
      By analyzing these configurations, it was found that there are regions of overlap
      in target size where a higher prescription IDL provides equivalent dose fall-off
      to a plan prescribed at the 50% IDL. Furthermore, the data indicate that
      treatment times within these regions can be reduced by up to 40%. An optimization
      strategy was devised to realize these gains. The strategy was tested for seven
      patients treated for 1-4 brain metastases (20 lesions total). RESULTS: For a
      single collimator setting, the gradient in the axial plane was steepest when
      prescribed to the 56-63% (4 mm), 62-70% (8 mm), and 77-84% (16 mm) IDL,
      respectively. Through utilization of the optimization technique, beam-on time was
      reduced by more than 15% in 16/20 lesions. The volume of normal brain receiving
      12 Gy or above also decreased in many cases, and in only one instance increased
      by more than 0.5 cm3. CONCLUSIONS: This work demonstrates that IDL optimization
      using the shot within shot technique can reduce treatment times without degrading
      treatment plan quality.

PMID- 29178911
TI  - Inhibition of HMGB1 reduces rat spinal cord astrocytic swelling and AQP4
      expression after oxygen-glucose deprivation and reoxygenation via TLR4 and NF
      kappaB signaling in an IL-6-dependent manner.
AB  - BACKGROUND: Spinal cord astrocyte swelling is an important component to spinal
      cord edema and is associated with poor functional recovery as well as therapeutic
      resistance after spinal cord injury (SCI). High mobility group box-1 (HMGB1) is a
      mediator of inflammatory responses in the central nervous system and plays a
      critical role after SCI. Given this, we sought to identify both the role and
      underlying mechanisms of HMGB1 in cellular swelling and aquaporin 4 (AQP4)
      expression in cultured rat spinal cord astrocytes after oxygen-glucose
      deprivation/reoxygenation (OGD/R). METHODS: The post-natal day 1-2 Sprague-Dawley
      rat spinal cord astrocytes were cultured in vitro, and the OGD/R model was
      induced. We first investigated the effects of OGD/R on spinal cord astrocytic
      swelling and HMGB1 and AQP4 expression, as well as HMGB1 release. We then studied
      the effects of HMGB1 inhibition on cellular swelling, HMGB1 and AQP4 expression,
      and HMGB1 release. The roles of both toll-like receptor 4 (TLR4)/nuclear factor
      kappa B (NF-kappaB) signaling pathway and interleukin-6 (IL-6) in reducing
      cellular swelling resulting from HMGB1 inhibition in spinal cord astrocytes after
      OGD/R were studied. Intergroup data were compared using one-way analysis of
      variance (ANOVA) followed by Dunnett's test. RESULTS: The OGD/R increased spinal
      cord astrocytic swelling and HMGB1 and AQP4 expression, as well as HMGB1 release.
      Inhibition of HMGB1 using either HMGB1 shRNA or ethyl pyruvate resulted in
      reduced cellular volume, mitochondrial and endoplasmic reticulum swelling, and
      lysosome number and decreased upregulation of both HMGB1 and AQP4 in spinal cord
      astrocytes, as well as HMGB1 release. The HMGB1 effects on spinal cord astrocytic
      swelling and AQP4 upregulation after OGD/R were mediated-at least in part-via
      activation of TLR4, myeloid differentiation primary response gene 88 (MyD88), and
      NF-kappaB. These activation effects can be repressed by TLR4 inhibition using CLI
      095 or C34, or by NF-kappaB inhibition using BAY 11-7082. Furthermore, either
      OGD/R or HMGB1 inhibition resulted in changes in IL-6 release. IL-6 was also
      shown to mediate AQP4 expression in spinal cord astrocytes. CONCLUSIONS: HMGB1
      upregulates AQP4 expression and promotes cell swelling in cultured spinal cord
      astrocytes after OGD/R, which is mediated through HMGB1/TLR4/MyD88/NF-kappaB
      signaling and in an IL-6-dependent manner.

PMID- 29178913
TI  - Identification of multiple cancer-associated myositis-specific autoantibodies in
      idiopathic inflammatory myopathies: a large longitudinal cohort study.
AB  - BACKGROUND: Cancer is a significant complication contributing to increased
      mortality in idiopathic inflammatory myopathies (IIMs), and the association
      between IIMs and cancer has been extensively reported. Myositis-specific
      autoantibodies (MSAs) can help to stratify patients into more homogeneous groups
      and may be used as a biomarker for cancer-associated myositis. In this study, we
      aimed to systematically define the cancer-associated MSAs in IIMs. METHODS: Serum
      from 627 patients with IIMs was tested for MSAs. The cancer risk with different
      MSAs was estimated by standardized incidence ratio (SIR). Paraneoplastic
      manifestation, such as the close temporal relationship between myositis onset and
      cancer diagnoses in patients with different MSAs, was also evaluated. RESULTS:
      Compared with the general Chinese population, patients with IIMs and anti
      transcriptional intermediary factor (TIF1)-gamma antibodies (SIR = 17.28, 95% CI
      11.94 to 24.14), anti-nuclear matrix protein (NXP2) antibodies (SIR = 8.14, 95%
      CI 1.63 to 23.86), or anti-SAE1 antibodies (SIR = 12.92, 95% CI 3.23 to 32.94),
      or who were MSAs-negative (SIR = 3.99, 95% CI 1.96 to 7.14) faced increased risk
      of cancer. There was no association between specific MSAs subtypes and certain
      types of cancer. Paraneoplastic manifestations were observed in the patients
      carrying anti-TIF1-gamma, as well as other MSAs. There were no prognostic
      differences among the patients with cancer-associated myositis (CAM) from
      different MSAs subgroups. However, in comparison to those with cancer unrelated
      to myositis, CAM had a worse prognosis, with an age-adjusted and sex-adjusted Cox
      hazard ratio (HR) of 10.8 (95% CI 1.38-84.5, p = 0.02) for all-cause mortality.
      CONCLUSIONS: Our study demonstrates in what is, to our knowledge, the largest
      population examined to date, that anti-SAE1, and previously reported anti-TIF1
      gamma and anti-NXP2 antibodies, are all associated with an increased risk of
      cancer in patients with IIMs. Moreover, our data suggest that in some cases, anti
      HMGCR, anti-Jo-1 and anti-PL-12 antibody production might also be driven by
      malignancy. This can aid in the etiologic research of paraneoplastic myositis and
      clinical management.

PMID- 29178914
TI  - Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase
      reduces brain damage and attenuates neuroinflammation after intracerebral
      hemorrhage.
AB  - BACKGROUND: Inflammatory responses significantly contribute to neuronal damage
      and poor functional outcomes following intracerebral hemorrhage (ICH). Soluble
      epoxide hydrolase (sEH) is known to induce neuroinflammatory responses via
      degradation of anti-inflammatory epoxyeicosatrienoic acids (EET), and sEH is
      upregulated in response to brain injury. The present study investigated the
      involvement of sEH in ICH-induced neuroinflammation, brain damage, and functional
      deficits using a mouse ICH model and microglial cultures. METHODS: ICH was
      induced by injecting collagenase in both wild-type (WT) C57BL/6 mice and sEH
      knockout (KO) mice. WT mice were injected intracerebroventricularly with 12-(3
      adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor, 30 min
      before ICH. Expression of sEH in the hemorrhagic hemisphere was examined by
      immunofluorescence and Western blot analysis. The effects of genetic deletion or
      pharmacological inhibition of sEH by AUDA on neuroinflammatory responses, EET
      degradation, blood-brain barrier (BBB) permeability, histological damage, and
      functional deficits were evaluated. The anti-inflammatory mechanism of sEH
      inactivation was investigated in thrombin- or hemin-stimulated cultured
      microglia. RESULTS: ICH induced an increase in sEH protein levels in the
      hemorrhagic hemisphere from 3 h to 4 days. sEH was expressed in
      microglia/macrophages, astrocytes, neurons, and endothelial cells in the
      perihematomal region. Genetic deletion of sEH significantly attenuated
      microglia/macrophage activation and expression of inflammatory mediators and
      reduced EET degradation at 1 and 4 days post-ICH. Deletion of sEH also reduced
      BBB permeability, matrix metalloproteinase (MMP)-9 activity, neutrophil
      infiltration, and neuronal damage at 1 and 4 days. Likewise, administration of
      AUDA attenuated proinflammatory microglia/macrophage activation and EET
      degradation at 1 day post-ICH. These findings were associated with a reduction in
      functional deficits and brain damage for up to 28 days. AUDA also ameliorated
      neuronal death, BBB disruption, MMP-9 activity, and neutrophil infiltration at 1
      day. However, neither gene deletion nor pharmacological inhibition of sEH altered
      the hemorrhage volume following ICH. In primary microglial cultures, genetic
      deletion or pharmacological inhibition of sEH by AUDA reduced thrombin- and hemin
      induced microglial activation. Furthermore, AUDA reduced thrombin- and hemin
      induced P38 MAPK and NF-kappaB activation in BV2 microglia cultures. Ultimately,
      AUDA attenuated N2A neuronal death that was induced by BV2 microglial conditioned
      media. CONCLUSIONS: Our results suggest that inhibition of sEH may provide a
      potential therapy for ICH by suppressing microglia/macrophage-mediated
      neuroinflammation.

PMID- 29178915
TI  - Longitudinal wall fractional shortening: an M-mode index based on mitral annular
      plane systolic excursion (MAPSE) that correlates and predicts left ventricular
      longitudinal strain (LVLS) in intensive care patients.
AB  - BACKGROUND: Left ventricular longitudinal strain (LVLS) is a modern measurement
      for LV function. However, strain measurement is often difficult in critically ill
      patients. We sought to show LVLS can be estimated using M-mode-derived
      longitudinal wall fractional shortening (LWFS), which is less dependent on image
      quality and is easier to perform in critically ill patients. METHODS:
      Transthoracic echocardiographic records were retrospectively screened and 80
      studies suitable for strain and M-mode measurements in the apical 4-chamber view
      were selected. Longitudinal wall fractional shortening was derived from
      conventional M-mode (LWFS) and curved anatomical M-mode (CAMMFS). The
      relationships between LVLS and mitral annular plane systolic excusion (MAPSE) and
      M-mode-derived fractional shortening were examined using univariate generalized
      linear model in a training set (n = 50) and was validated in a separate
      validation set (n = 30). RESULTS: MAPSE, CAMMFS, and LWFS demonstrated very good
      correlations with LVLS (r = 0.852, 0.875 and 0.909, respectively). LWFS was the
      best unbiased predictor for LVLS (LVLS = 1.180 x LWFS - 0.737, P < 0.001). Intra-
      and inter-rater agreement and reliability for LWFS measurement were good.
      CONCLUSIONS: LVLS can be estimated by LWFS in the critically ill patients. It
      provides a fast and accurate prediction of LVLS. LWFS is a reproducible and
      reliable measurement which can be used as a potential index in place of LVLS in
      the critically ill population.

PMID- 29178916
TI  - Do hedonic- versus nutrition-based attitudes toward food predict food choices? a
      cross-sectional study of 6- to 11-year-olds.
AB  - BACKGROUND: Implicit and explicit attitudes are potential precursors of food
      choices and combine affective and cognitive components that can vary in their
      relative dominance. Yet, the affective and cognitive components of attitudes
      toward food can lead to distinct predisposition toward a food item and
      potentially to different food choices. In the food domain, the affective
      component pertains to the hedonic tone of consumption, while the cognitive
      component encompasses nutritional value or health consequences of food. The
      present study investigated whether hedonic- versus nutrition-based implicit
      and/or explicit attitudes toward food predicts children's healthy versus
      unhealthy food choices. METHODS: A total of 63 children (age range = 6.3-11.5)
      participated in a 90-min session at 5 pm (i.e., afterschool snack time in
      France). The children were asked to choose five food items from a buffet
      featuring five healthy and five unhealthy sweet foods pretested as being highly
      liked. Children ate what they had chosen. Moreover, their implicit attitudes were
      assessed with a pairing task in which children were presented with 10 food
      triplets and asked to choose two food items that "best go together". For each
      triplet, foods could be paired according to their hedonic or nutritional
      characteristics. Explicit attitudes were assessed with a task in which children
      placed each of 48 food items into one of the following categories: "yummy",
      "yucky" (i.e., hedonic categories), "makes you strong", or "makes you fat" (i.e.,
      nutritional categories). RESULTS: Both implicit and explicit attitudes
      significantly influenced children's food choices. We observed that children with
      more hedonic-based implicit or explicit attitudes toward food were more likely to
      choose healthy food options from the buffet. Conversely, children with both
      implicit and explicit nutrition-based attitudes chose less healthy foods.
      CONCLUSIONS: Hedonic-based attitudes toward food seem to drive healthier food
      choices in children compared with nutrition-based attitudes in this particular
      eating context. These findings suggest that pleasure from eating might be an ally
      with regard to healthy eating among children. Additional research is needed to
      understand the etiology of children's attitudes toward food in order to provide
      insights on how to shape adequate children's attitudes to guide them toward
      healthy food choices.

PMID- 29178917
TI  - The influence of surface EMG-triggered multichannel electrical stimulation on
      sensomotoric recovery in patients with lumbar disc herniation: study protocol for
      a randomized controlled trial (RECO).
AB  - BACKGROUND: Intervertebral disc degeneration is one of the most common reasons
      for chronic low back pain and sensomotoric deficits, often treated by lumbar
      sequestrectomy. Nevertheless, the prognostic factors relevant for time and
      quality of recovery, of the surgical procedure, relative to conservative
      treatment, remain controversial and require further investigation. Surface
      electrical stimulation (SES) may be an influential intervention, already showing
      positive impact on motor and sensory recovery in different patient groups. Since
      mechanisms of SES still remain unclear, further inquiry is needed.
      METHODS/DESIGN: This is a prospective, monocentric, randomized, controlled
      clinical trial. A total of 80 adult patients suffering from a lumbar disc
      herniation (LDH; 40 treated surgically, 40 conservatively) are allocated in a
      ratio of 1:1. Patients in the treatment group will receive surface
      electromyography (EMG)-triggered electrical stimulation for eight weeks, whereas
      patients in the control group will not obtain any additional treatment. The
      primary outcome parameter is defined as the cold detection threshold (CDT),
      determined by quantitative sensory testing (QST), 24 months after intervention.
      Secondary outcome parameters include the inquiry of sensory nerve function by two
      point discrimination and QST, the assessment of motor nerve function by manual
      muscle testing, and validated scales and scores. These include: the Oswestry
      Disability Index (ODI) and the Core Outcome Measures Index (COMI) assessing the
      domains pain, back-specific function, work disability, and patient satisfaction;
      the EQ-5D investigating the patient's generic health status; the painDETECT
      questionnaire (PD-Q) to identify neuropathic pain components; and the Beck
      Depression Inventory (BDI) to assess severity of depression. Moreover,
      neurological status, pain medication usage, and blood samples (CRP, TNFalpha, IL
      1beta, IL-6) will be evaluated. Study data generation (study site) and data
      storage, processing, and statistical analysis are clearly separated. DISCUSSION:
      The results of the RECO study will detect the effect of EMG-triggered
      multichannel SES on the improvement of mechanical and thermal sensitivity and the
      effect on motor recovery and pain, associated with clinical and laboratory
      parameters. Furthermore, data comparing surgical and conservative treatment can
      be collected. This will hopefully allow treatment recommendations for patients
      with LDH accompanied by a sensomotoric deficit. TRIAL REGISTRATION: ISRCTN,
      ISRCTN12741173 . Registered on 15 January 2017.

PMID- 29178918
TI  - Health state utilities associated with attributes of weekly injection devices for
      treatment of type 2 diabetes.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are often
      recommended as part of combination therapy for type 2 diabetes when oral
      medication does not result in sufficient glycemic control. Several GLP-1 receptor
      agonists are available as weekly injections. These medications vary in their
      injection delivery systems, and these differences could impact quality of life
      and treatment preference. The purpose of this study was to estimate utilities
      associated with attributes of injection delivery systems for weekly GLP-1
      therapies. METHODS: Participants with type 2 diabetes in the UK valued health
      states in time trade-off interviews. The health states (drafted based on
      literature, device instructions for use, and clinician interviews) had identical
      descriptions of type 2 diabetes, but differed in description of the treatment
      process. One health state described oral treatment, while six others described
      oral treatment plus a weekly injection. The injection health states varied in
      three aspects of the treatment administration process: requirements for
      reconstituting the medication (i.e., mixing the medication prior to the
      injection), waiting during medication preparation, and needle handling. Every
      participant valued all seven health states. RESULTS: A total of 209 participants
      completed interviews (57.4% male; mean age = 60.4y). The mean utility of the oral
      treatment health state was 0.89. All injection health states had significantly (p
      < 0.01) lower utilities ranging from 0.86 to 0.88. Differences among health state
      utilities suggest that each administration requirement had a small but
      measureable disutility: -0.004 (reconstitution), -0.004 (needle handling), -0.010
      (reconstitution, needle handling), and -0.020 (reconstitution, waiting, needle
      handling). CONCLUSIONS: Findings suggest it is feasible to use the TTO method to
      quantify preferences among injection treatment processes. It may be useful to
      incorporate these utility differences into cost-utility models comparing weekly
      injectable treatments for patients with type 2 diabetes.

PMID- 29178919
TI  - Double lung, unlike single lung transplantation might provide a protective effect
      on mortality and bronchiolitis obliterans syndrome.
AB  - BACKGROUND: Survival after lung transplantation (LTx) is often limited by
      bronchiolitis obliterans syndrome (BOS). METHOD: Survey of 278 recipients who
      underwent LTx. The endpoint used was BOS (BOS grade >= 2), death or Re-lung
      transplantation (Re-LTx) assessed by competing risk regression analyses. RESULTS:
      The incidence of BOS grade >= 2 among double LTx (DLTx) recipients was 16 +/- 3%
      at 5 years, 30 +/- 4% at 10 years, and 37 +/- 5% at 20 years, compared to single
      LTx (SLTx) recipients whose corresponding incidence of BOS grade >= 2 was 11 +/-
      3%, 20 +/- 4%, and 24 +/- 5% at 5, 10, and 20 years, respectively (p > 0. 05).
      The incidence of BOS grade >= 2 by major indications ranked in descending order:
      other, PF, CF, COPD, PH and AAT1 (p < 0. 05). The mortality rate by major
      indication ranked in descending order: COPD, PH, AAT1, PF, Other and CF (p < 0.
      05). CONCLUSION: No differences were seen in the incidence of BOS grade >= 2
      regarding type of transplant, however, DLTx recipients showed a better chance of
      survival despite developing BOS compared to SLTx recipients. The highest
      incidence of BOS was seen among CF, PF, COPD, PH, and AAT1 recipients in
      descending order, however, CF and PF recipients showed a better chance of
      survival despite developing BOS compared to COPD, PH, and AAT1 recipients.

PMID- 29178920
TI  - The gut mycobiome of the Human Microbiome Project healthy cohort.
AB  - BACKGROUND: Most studies describing the human gut microbiome in healthy and
      diseased states have emphasized the bacterial component, but the fungal
      microbiome (i.e., the mycobiome) is beginning to gain recognition as a
      fundamental part of our microbiome. To date, human gut mycobiome studies have
      primarily been disease centric or in small cohorts of healthy individuals. To
      contribute to existing knowledge of the human mycobiome, we investigated the gut
      mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal
      Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene. RESULTS: Three
      hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal
      fungal diversity was significantly lower in comparison to bacterial diversity.
      Yeast dominated the samples, comprising eight of the top 15 most abundant genera.
      Specifically, fungal communities were characterized by a high prevalence of
      Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C.
      albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of
      samples, respectively. There was a high degree of inter- and intra-volunteer
      variability in fungal communities. However, S. cerevisiae, M. restricta, and C.
      albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in
      all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA
      gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided
      greater resolution of the relatively low abundance mycobiome constituents.
      CONCLUSIONS: Compared to bacterial communities, the human gut mycobiome is low in
      diversity and dominated by yeast including Saccharomyces, Malassezia, and
      Candida. Both inter- and intra-volunteer variability in the HMP cohort were high,
      revealing that unlike bacterial communities, an individual's mycobiome is no more
      similar to itself over time than to another person's. Nonetheless, several fungal
      species persisted across a majority of samples, evidence that a core gut
      mycobiome may exist. ITS2 sequencing data provided greater resolution of the
      mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data,
      suggesting that it is a more sensitive method for studying the mycobiome of stool
      samples.

PMID- 29178921
TI  - Plasmodium falciparum Kelch 13 mutations and treatment response in patients in
      Hpa-Pun District, Northern Kayin State, Myanmar.
AB  - BACKGROUND: Artemisinin resistance, linked to polymorphisms in the Kelch gene on
      chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in
      South East Asia. For national malaria control programmes in the region, it is
      important to establish a surveillance system which includes monitoring for k13
      polymorphisms associated with the clinical phenotype. METHODS: Between February
      and December 2013, parasite clearance was assessed in 35 patients with
      uncomplicated P. falciparum treated with artesunate monotherapy followed by 3-day
      ACT in an isolated area on the Myanmar-Thai border with relatively low
      artemisinin drug pressure. Molecular testing for k13 mutations was performed on
      dry blood spots collected on admission. RESULTS: The proportion of k13 mutations
      in these patients was 41.7%, and only 5 alleles were detected: C580Y, I205T,
      M476I, R561H, and F446I. Of these, F446I was the most common, and was associated
      with a longer parasite clearance half-life (median) 4.1 (min-max 2.3-6.7) hours
      compared to 2.5 (min-max 1.6-8.7) in wildtype (p = 0.01). The prevalence of k13
      mutant parasites was much lower than the proportion of k13 mutants detected 200
      km south in a much less remote setting where the prevalence of k13 mutants was
      84% with 15 distinct alleles in 2013 of which C580Y predominated. CONCLUSIONS:
      This study provides evidence of artemisinin resistance in a remote part of
      eastern Myanmar. The prevalence of k13 mutations as well as allele diversity
      varies considerably across short distances, presumably because of historical
      patterns of artemisinin use and population movements.

PMID- 29178922
TI  - Elevated plasma levels of lysophosphatidic acid and aberrant expression of
      lysophosphatidic acid receptors in adenomyosis.
AB  - BACKGROUND: Given the important roles of the receptor-mediated lysophosphatidic
      acid (LPA) signaling in both reproductive tract function and gynecological
      cancers, it will be informative to investigate the potential role of LPA in the
      development of adenomyosis. The objective of this study was to evaluate the
      levels of LPA in plasma and the expression of six LPA receptors in the
      endometrial tissue collected from women with and without adenomyosis. METHODS:
      Plasma and endometrial tissue samples were collected form women with and without
      adenomyosis. The levels of LPA in plasma were determined by using high
      performance liquid chromatography electrospray ionization tandem mass
      spectrometry (HPLC-ESI-MS/MS). Immunohistochemistry was performed to evaluate the
      expression of six LPA receptors (LPA1-6) in endometrial tissue samples. The
      effects of LPA on IL-8 production, VEGF production and cell proliferation in
      human endometrial stromal cells (ESCs) were also assessed. RESULTS: LPA1 staining
      was localized to the cytoplasm, membrances of the epithelial cells of the
      endometrial glands, and there was little staining in the stromal cells. LPA2-5
      staining were localized to the nuclei of stromal and glandular cells. Plasma
      levels of LPA were increased in adenomyosis. LPA1, LPA4 and LPA5 immunoreactivity
      were significantly higher in the adenomyosis group than in the control group,
      while LPA2 and LPA3 immunoreactivity were significantly lower in the adenomyosis
      group than in the control group. LPA6 was undetectable in the endometria. LPA
      induced the release of IL-8 from ESCs but did not affect cell proliferation and
      VEGF production. CONCLUSION: These results indicate that elevated plasma levels
      of LPA and aberrant expression of LPA receptors in the endometria may be
      associated with the development of adenomyosis.

PMID- 29178923
TI  - Guided self-determination-young versus standard care in the treatment of young
      females with type 1 diabetes: study protocol for a multicentre randomized
      controlled trial.
AB  - BACKGROUND: Female adolescents with type 1 diabetes mellitus (T1DM) have the most
      unsatisfactory glycaemic control of all age groups and report higher disease
      burden, poorer perceived health, and lower quality of life than their male
      counterparts. Females with T1DM face an excess risk of all-cause mortality
      compared with men with T1DM. New methods are needed to help and support young
      females with T1DM to manage their disease. A prerequisite for successful diabetes
      management is to offer individualized, person-centred care and support the
      patient's own motivation. Guided self-determination (GSD) is a person-centred
      reflection and problem-solving method intended to support the patient's own
      motivation in the daily care of her diabetes and help develop skills to manage
      difficulties in diabetes self-management. GSD has been shown to improve glycaemic
      control and decrease psychosocial stress in young women with T1DM. The method has
      been adapted for adolescents and their parents, termed GSD-young (GSD-Y). The aim
      of this study was to evaluate whether an intervention with GSD-Y in female
      adolescents with T1DM leads to improved glycaemic control, self-management,
      treatment satisfaction, perceived health and quality of life, fewer diabetes
      related family conflicts, and improved psychosocial self-efficacy.
      METHODS/DESIGN: This is a parallel-group randomized controlled superiority trial
      with an allocation ratio of 1:1. One hundred female adolescents with T1DM, 15-20
      years of age, and their parents (if < 18 years of age), will be included. The
      intervention group will receive seven individual GSD-Y education visits over 3 to
      6 months. The control group will receive standard care including regular visits
      to the diabetes clinic. The primary outcome is level of glycaemic control,
      measured as glycosylated haemoglobin (HbA1c). Secondary outcomes include diabetes
      self-management, treatment satisfaction, perceived health and quality of life,
      diabetes-related family conflicts, and psychosocial self-efficacy. Data will be
      collected before randomization and at 6 and 12 months. DISCUSSION: Poor glycaemic
      control is common in female adolescents and young adults with T1DM. Long-standing
      hyperglycaemia increases the risks for severe complications and may also have an
      adverse impact on the outcome of future pregnancies. In this study, we want to
      evaluate if the GSD-Y method can be a useful tool in the treatment of female
      adolescents with T1DM. TRIAL REGISTRATION: Current controlled trials,
      ISRCTN57528404 . Registered on 18 February 2015.

PMID- 29178924
TI  - Instruments evaluating the self-directed learning abilities among nursing
      students and nurses: a systematic review of psychometric properties.
AB  - BACKGROUND: Modern healthcare institutions are continuously changing, and Self
      Directed Learning (SDL) abilities are considered a prerequisite for both nursing
      students and nurses in order to be proactive about these demanding challenges. To
      date, no systematic reviews of existing instruments aimed at detecting and
      critically evaluating SDL abilities have been published. Therefore, the aims of
      this review are: 1) identify the instruments for assessment of SDL abilities
      among nursing students and nurses; 2) critically evaluate the methodological
      studies quality; and 3) compare the psychometric properties of the available
      instruments. METHODS: A psychometric-systematic-review was performed. CDSR,
      CINAHL, ERIC, MEDLINE, PROSPERO, SCOPUS databases were searched without
      restrictions in time and setting. All primary studies involving nursing students
      or nurses, written in English and aimed at validating SDL assessment tools, were
      included. Studies retrieved were evaluated according to the COnsensus-based
      Standards for the selection of health Measurement-INstruments (COSMIN) panel.
      Study inclusion, data extraction and quality assessment were performed by
      researchers independently. RESULTS: Eleven studies were included and four tools
      based on Knowles's theory have emerged: 1) the Self-Directed Learning Readiness
      Scale; 2) the Self-Directed Learning Readiness Scale for Nursing Education; 3)
      the Self-Rating Scale of Self-Directed Learning, and 4) the Self-Directed
      Learning Instrument. A few psychometric properties have been considered in each
      study, from two to four out of the ten required. The quality of the methodologies
      used was in general, from fair to poor with the exception of one instrument (the
      Self-Directed-Learning-Instrument). The psychometric proprieties that emerged
      across the tools were good in general: the Cronbach alpha was from 0.73 to 0.91;
      structural validities have also reported good indexes both in the explorative and
      in the confirmative factor analyses. CONCLUSIONS: On the basis of the findings,
      the Self-Directed-Learning-Instrument can be recommended for the assessment of
      SDL abilities among nursing students and nurses, given the excellent methodology
      quality adopted in estimating the psychometric properties. However, rigorous
      study designs aimed at estimating psychometric properties of tools in wide
      samples of nursing students and nurses across different stages of professional
      life, from undergraduate education to professional maturity, in different
      cultural, educational, and work settings, are strongly recommended.

PMID- 29178925
TI  - Expediting citation screening using PICo-based title-only screening for
      identifying studies in scoping searches and rapid reviews.
AB  - BACKGROUND: Citation screening for scoping searches and rapid review is time
      consuming and inefficient, often requiring days or sometimes months to complete.
      We examined the reliability of PICo-based title-only screening using keyword
      searches based on the PICo elements-Participants, Interventions, and Comparators,
      but not the Outcomes. METHODS: A convenience sample of 10 datasets, derived from
      the literature searches of completed systematic reviews, was used to test PICo
      based title-only screening. Search terms for screening were generated from the
      inclusion criteria of each review, specifically the PICo elements-Participants,
      Interventions and Comparators. Synonyms for the PICo terms were sought, including
      alternatives for clinical conditions, trade names of generic drugs and
      abbreviations for clinical conditions, interventions and comparators. The MeSH
      database, Wikipedia, Google searches and online thesauri were used to assist
      generating terms. Title-only screening was performed by five reviewers
      independently in Endnote X7 reference management software using OR Boolean
      operator. Outcome measures were recall of included studies and the reduction in
      screening effort. Recall is the proportion of included studies retrieved using
      PICo title-only screening out of the total number of included studies in the
      original reviews. The percentage reduction in screening effort is the proportion
      of records not needing screening because the method eliminates them from the
      screen set. RESULTS: Across the 10 reviews, the reduction in screening effort
      ranged from 11 to 78% with a median reduction of 53%. In nine systematic reviews,
      the recall of included studies was 100%. In one review (oxygen therapy), four of
      five reviewers missed the same included study (median recall 67%). A post hoc
      analysis was performed on the dataset with the lowest reduction in screening
      effort (11%), and it was rescreened using only the intervention and comparator
      keywords and omitting keywords for participants. The reduction in screening
      effort increased to 57%, and the recall of included studies was maintained
      (100%). CONCLUSIONS: In this sample of datasets, PICo-based title-only screening
      was able to expedite citation screening for scoping searches and rapid reviews by
      reducing the number of citations needed to screen but requires a thorough workup
      of the potential synonyms and alternative terms. Further research which evaluates
      the feasibility of this technique with heterogeneous datasets in different fields
      would be useful to inform the generalisability of this technique.

PMID- 29178926
TI  - Letter to the Editor regarding the article: "identifying pre-hospital factors
      associated with outcome for major trauma patients in a regional trauma network:
      an exploratory study".
AB  - The aim of this Letter to the Editor was to report some methodological
      shortcomings in a recently published article. Issues regarding missing values and
      overfitting are mentioned. First, Complete Case (CC) analysis was used instead of
      an imputation method. Second, there was a high chance of overfitting and lack of
      model validation. In conclusion, the results of this study should be interpret
      with caution and further research is necessary.

PMID- 29178927
TI  - Why is there still hepatitis C transmission in Australian prisons? A case report.
AB  - BACKGROUND: The ability to cure hepatitis C viral infection, with specific
      reference to the prisoner population and the prison environment, will be
      challenged, even if opiate replacement therapy is concurrently offered, and even
      if bleach is available. The missing elements, widely available in the community,
      are a regulated injecting equipment exchange and tattooing parlours. CASE
      PRESENTATION: We report a case of re-infection of hepatitis C in a prisoner
      treated with a direct-acting antiviral. What makes this case so remarkable is
      that it was entirely predictable and preventable. CONCLUSIONS: Hepatitis C
      infection will continue to test both the strengths and the weaknesses in the
      relationship between health and corrective services in Australia. Nothing less
      than full implementation of all harm minimisation modalities will be necessary to
      eliminate the clinical and public health risks of hepatitis C infection, both in
      prison and by extension into the general community.

PMID- 29178929
TI  - Serological prevalence and public health significance of brucellosis on a dairy
      farm in Namibia from 2011 to 2014.
AB  - OBJECTIVE: The main objective of this study was to determine the serological
      prevalence of brucellosis on a dairy farm with no past history of abortions, but
      where Brucella control measures including test and slaughter and vaccination of
      heifers at 4-8 months of age was practiced. Secondary data from 2011 to 2014
      obtained from the Epidemiology Section of the Directorate of Veterinary Services
      was used. RESULTS: Mandatory annual brucellosis testing results for mature dairy
      cows on a dairy farm for the period 2011-2014 were collated and analyzed. Results
      of a total of 6912 cows were analysed. The data comprised of the year of testing,
      number of cows tested for Brucella antibodies and the number of cows that tested
      positive. Serological testing was carried out using the Rose Bengal Test (RBT) as
      a screening test and the Complement Fixation Test as a confirmatory test for
      results that tested positive on the RBPT. Over the 4-year period, one dairy cow
      tested positive for Brucella antibodies in 2013 giving an apparent prevalence of
      0.05% and an overall prevalence of 0.01%. When apparent prevalence was adjusted
      for RBPT test specificity and sensitivity of 71 and 78% respectively, true
      prevalence was determined to be zero.

PMID- 29178928
TI  - MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem
      cells on acute myocardial infarction.
AB  - BACKGROUND: Our study aim was to evaluate the therapeutic efficacy and mechanisms
      of miR-133-overexpressing mesenchymal stem cells (MSCs) on acute myocardial
      infarction. METHODS: Rat MSCs were isolated and purified by whole bone marrow
      adherent culturing. After transfection with the agomir or antagomir of miR-133,
      MSCs were collected for assay of cell vitality, apoptosis, and cell cycle
      progression. At the same time, exosomes were isolated from the supernatant to
      analyze the paracrine miR-133. For in-vivo studies, constitutive activation of
      miR-133 in MSCs was achieved by lentivirus-mediated miR-133 overexpression. A rat
      myocardial infarction model was created by ligating the left anterior descending
      coronary artery, while control MSCs (vector-MSCs) or miR-133-overexpressed MSCs
      (miR-133-MSCs) were injected into the zone around the myocardial infarction.
      Subsequently, myocardial function was evaluated by echocardiography on days 7 and
      28 post infarction. Finally the infarcted hearts were collected on days 7 and 28
      for myocardial infarct size measurement and detection of snail 1 expression.
      RESULTS: Hypoxia-induced apoptosis of MSCs obviously reduced, along with enhanced
      expression of total poly ADP-ribose polymerase protein, after miR-133 agomir
      transfection, while the apoptosis rate increased in MSCs transfected with miR-133
      antagomir. However, no change in cell viability and cell-cycle distribution was
      observed in control, miR-133-overexpressed, and miR-133-interfered MSCs.
      Importantly, rats transplanted with miR-133-MSCs displayed more improved cardiac
      function after acute myocardial infarction, compared with those that received
      vector-MSC injection. Further studies indicated that cardiac expression of snail
      1 was significantly repressed by adjacent miR-133-overexpressing MSCs, and both
      the inflammatory level and the infarct size decreased in miR-133-MSC-injected rat
      hearts. CONCLUSIONS: miR-133-MSCs obviously improved cardiac function in a rat
      model of myocardial infarction. Transplantation of miR-133-overexpressing MSCs
      provides an effective strategy for cardiac repair and modulation of cardiac
      related diseases.

PMID- 29178930
TI  - An Msh3 ATPase domain mutation has no effect on MMR function.
AB  - OBJECTIVE: To demonstrate that the Msh3 ATPase domain is required for DNA
      mismatch repair and tumor suppression in a murine model. RESULTS: The DNA
      mismatch repair proteins are members of the ABC family of ATPases. ATP binding
      and hydrolysis regulates their mismatch repair function. In the current study, a
      mouse model was generated harboring a glycine to aspartic acid residue change in
      the Walker A motif of the ATPase domain of Msh3. Impaired ATP mediated release of
      the Msh2-Msh3 GD/GD complex from it's DNA substrate in vitro confirmed the
      presence of an ATPase defect. However, the mismatch repair function of the
      protein was not significantly affected. Therefore, mutation of a critical residue
      within the ATPase domain of Msh3 did not preclude mismatch repair at the genomic
      sequences tested. Indicating that Msh3 mediated mismatch function is retained the
      absence of a functional ATPase domain.

PMID- 29178931
TI  - Anatomy of the sacroiliac joints in children and adolescents by computed
      tomography.
AB  - BACKGROUND: Diagnosing sacroiliitis by magnetic resonance imaging (MRI) in
      children/adolescents can be difficult due to the growth-related changes. This
      study analyzed the normal osseous anatomy of the sacroiliac joints (SIJ) in a
      juvenile population using computed tomography (CT). METHODS: The anatomy of the
      SIJ was retrospectively analyzed in 124 trauma patients aged 9 months - <18 years
      by CT, based on 2 mm slices in axial, semi-axial and semi-coronal planes. The
      following anatomical features were recorded: intersegmental fusion of the sacral
      vertebral segments 1-3 (S1-S3), ossified nuclei (antero-superior at S1, lateral
      to the intervertebral spaces and lateral to S1 and S2) and joint facet defects
      larger than 3 mm. RESULTS: Fusion of S1/S2 started at the age of 6 years and was
      complete after the age of 13 years in most girls and after the age of 14 years in
      most boys. Fusion of S2/S3 started at the age of 9 years, but could remain
      incomplete up to 18 years in both genders. Ossified nuclei antero-lateral at S1
      and/or in the joint space were observed until the age of 18 years and occurred in
      77% of individuals >=13 years with intraarticular localization in 64% of girls
      and 60% of boys. Joint facet defects >3 mm occurred in 21 children/adolescents
      (17%) located to both the iliac and sacral joint facets. CONCLUSIONS: Normal
      osseous SIJ structures in children and adolescents vary considerably. Attention
      to these normal anatomical structures during growth may help to avoid false
      positive findings by MRI.

PMID- 29178932
TI  - Herbst appliance with skeletal anchorage versus dental anchorage in adolescents
      with Class II malocclusion: study protocol for a randomised controlled trial.
AB  - BACKGROUND: The Herbst appliance is an orthodontic appliance that is used for the
      correction of class II malocclusion with skeletal discrepancies. Research has
      shown that this is effective. However, a potential harm is excessive protrusion
      of the lower front teeth. This is associated with gingival recession, loss of
      tooth support, and root resorption. This trial evaluates a method of reducing
      this problem. METHODS/DESIGN: The study is a single-center, randomised, assessor
      blinded, superiority clinical trial with parallel 1:1 allocation. Male and female
      young people (10-14 years old) with prominent front teeth (class II, division 1)
      will be treated in one orthodontic clinic. Group 1 will be treated with the
      conventional Herbst appliance with dental anchorage and group 2 with the Herbst
      appliance with indirect skeletal anchorage for 12 months. The primary objective
      will be to compare the proclination of the lower incisors between the Herbst
      appliance with dental anchorage and skeletal anchorage. Secondary objectives will
      be to evaluate the changes occurring between the groups in the mandible, maxilla,
      lower and upper molars, and in gingival recession and root resorption at the end
      of the treatment. Additionally, the young patient's experience using the
      appliances will be assessed. The primary outcome measure will be the amount of
      lower incisor proclination at the end of treatment. This will be assessed by cone
      beam computed tomography (CBCT) superimposition. Secondary outcome measures will
      be the changes in the mandible, maxilla, lower and upper molars at the end of
      treatment assessed by tomography superimposition and the young patient's
      experience using the appliances assessed by self-reported questionnaires and semi
      structured interviews. The randomisation method will be blocked randomisation,
      using software to generate a randomised list. The allocation concealment will be
      done in opaque envelopes numbered from 1 to 40 containing the treatment modality.
      The randomisation will be implemented by the secretary of the Department of
      Orthodontics of Rio de Janeiro State University before the beginning of the
      study. The patients and the orthodontists who will treat the patients cannot be
      blinded, as they will know the type of appliance used. The technician who will
      take the CBCT image and the data analyst will be blinded to patients' group
      allocation. DISCUSSION: If this new intervention is effective, the findings can
      change orthodontic practice and may also be relevant to other forms of treatment
      in which appliances are fixed to the bones of the jaws. However, if the bone
      anchoring is not effective, the trial will provide much needed information on the
      use of this comparatively new development. TRIAL REGISTRATION:
      ClinicalTrials.gov, protocol ID: NCT0241812 . Registered on 26 March 2015.

PMID- 29178934
TI  - Effectiveness of case management in the prevention of COPD re-admissions: a pilot
      study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations are
      associated with high disease burden and costs, especially in the case of
      hospitalizations. The overall number of hospital admissions due to exacerbations
      of COPD has increased. It is remarkable that re-admissions account for a
      substantial part of these hospitalizations. This pilot study investigates the use
      of case management to reduce re-admissions due to COPD. METHODS: COPD patients
      with more than one hospitalization per year due to an exacerbation were included.
      The participants (n = 10) were closely monitored and intensively coached for 20
      weeks after hospitalization. The case manager provided care in a person-focused
      manner. The case manager informed and supported the patient, took action when
      relapse threatened, coordinated and connected primary and secondary care. Data of
      12 months before and after start of the intervention were compared. Primary
      outcome was the difference in number of hospitalizations. Secondary outcomes were
      health-related quality of life (measured by the Clinical COPD Questionnaire, CCQ)
      and dyspnoea (measured by the MRC Dyspnoea Scale). RESULTS: The incidence rate of
      hospitalizations was found to be 2.25 times higher (95% confidence interval [CI]
      1.3-3.9; P = 0.004) 12 months before compared with 12 months after the start of
      case management. COPD patients had a mean CCQ score of 3.3 (95% CI 2.8-3.8)
      before and 2.4 (95% CI 1.9-2.8) after 20 weeks of case management; a difference
      of 1.0 (95% CI 0.4-1.6; P = 0.001). The mean MRC scores showed no significant
      differences before (4.3; 95% CI 3.7-4.9) and after the case management period
      (3.9; 95% CI 3.2-4.6); a difference of 0.4 (95% CI - 0.1 to 0.9; P = 0.114).
      CONCLUSIONS: This pilot study shows that the number of COPD hospital re
      admissions decreased significantly after the introduction of a case manager.
      Moreover, there was an improvement in patient-reported health-related quality of
      life.

PMID- 29178933
TI  - The chronically inflamed central nervous system provides niches for long-lived
      plasma cells.
AB  - Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of
      multiple sclerosis diagnosis for over three decades, the role of antibody
      secreting cells in multiple sclerosis remains unclear. T and B cells are critical
      for multiple sclerosis pathogenesis, but increasing evidence suggests that plasma
      cells also contribute, through secretion of autoantibodies. Long-lived plasma
      cells are known to drive various chronic inflammatory conditions as e.g. systemic
      lupus erythematosus, however, to what extent they are present in autoimmune
      central nervous system inflammation has not yet been investigated. In brain
      biopsies from multiple sclerosis patients and other neurological diseases, we
      could detect non-proliferating plasma cells (CD138+Ki67-) in the parenchyma.
      Based on this finding, we hypothesized that long-lived plasma cells can persist
      in the central nervous system (CNS). In order to test this hypothesis, we adapted
      the multiple sclerosis mouse model experimental autoimmune encephalomyelitis to
      generate a B cell memory response. Plasma cells were found in the meninges and
      the parenchyma of the inflamed spinal cord, surrounded by tissue areas resembling
      survival niches for these cells, characterized by an up-regulation of chemokines
      (CXCL12), adhesion molecules (VCAM-1) and survival factors (APRIL and BAFF). In
      order to determine the lifetime of plasma cells in the chronically inflamed CNS,
      we labeled the DNA of proliferating cells with 5-ethynyl-2'-deoxyuridine (EdU).
      Up to five weeks later, we could detect EdU+ long-lived plasma cells in the
      murine CNS. To our knowledge, this is the first study describing non
      proliferating plasma cells directly in the target tissue of a chronic
      inflammation in humans, as well as the first evidence demonstrating the ability
      of plasma cells to persist in the CNS, and the ability of the chronically
      inflamed CNS tissue to promote this persistence. Hence, our results suggest that
      the CNS provides survival niches for long-lived plasma cells, similar to the
      niches found in other organs. Targeting these cells in the CNS offers new
      perspectives for treatment of chronic autoimmune neuroinflammatory diseases,
      especially in patients who do not respond to conventional therapies.

PMID- 29178935
TI  - Estimating annual prevalence of depression and anxiety disorder in multiple
      sclerosis using administrative data.
AB  - OBJECTIVE: Researchers have developed case definitions to estimate incidence and
      lifetime prevalence of depression and anxiety disorders in multiple sclerosis
      (MS) using administrative data. For policymakers however, the prevalence of a
      disease requiring ongoing treatment during a given period such as annual period
      prevalence may be more relevant for decision-making. We tested a case definition
      for annual period prevalence of depression and anxiety disorders in MS using
      administrative data. RESULTS: Using population-based administrative (health
      claims) data from Manitoba, Canada we identified 1922 persons with incident MS
      from 1989 to 2012, and 11,392 age, sex and geographically-matched controls from
      the general population. As compared to controls, MS patients had an elevated
      annual prevalence ratio of depression (1.77; 95% confidence interval [CI] 1.64,
      1.91), and anxiety disorders (1.46; 95% CI 1.35, 1.58). The annual prevalence of
      depression in our matched cohort was similar to that observed in the 2012
      Canadian Community Health Survey, although the annual prevalence of anxiety was
      slightly higher. Administrative data can be used to estimate the annual period
      prevalence of psychiatric disorders in MS.

PMID- 29178936
TI  - Diallyl disulphide inhibits apolipoprotein(a) expression in HepG2 cells through
      the MEK1-ERK1/2-ELK-1 pathway.
AB  - BACKGROUND: Lipoprotein(a) [LP(a)] is implicated as a common and independent risk
      factor for cardiovascular diseases. The therapeutic options currently available
      for reducing plasma LP(a) concentrations are limited. Diallyl disulphide (DADS),
      the main component of garlic, regulates lipid metabolism in hepatocytes and
      adipocytes through ERK1/2 signalling. This study aimed to assess the effect of
      DADS on apolipoprotein(a) [apo(a)] in HepG2 cells. We also determined the effects
      of DADS on apo(a) expression and secretion in HepG2 cells as well as the
      underlying mechanisms. METHODS: We examined the role of DADS on apo(a) expression
      in HepG2 cells by treating cell with different concentrations of DADS (10, 20, 40
      and 80 MUg/mL) for 24 h or treating cells with 40 MUg/mL DADS for 0, 6, 12, 24
      and 48 h. Then we used quantitative real-time PCR to analysis apo(a) mRNA levels,
      used Western blot to analysis apo(a) protein levels and used enzyme-linked
      immunosorbent assay to test apo(a) secreted levels. To farther determined the
      role of DADS, we applied Transfection of small interfering RNA to knockdown ELK
      1levels and applied PD98059, a specific inhibitor of ERK1/2, to block ERK1/2
      signal. RESULTS: The results show DADS inhibited apo(a) at both the mRNA and
      protein levels in HepG2 cells in a dose-dependent manner. DADS-mediated
      inhibition of apoa(a) expression in HepG2 cells was attenuated when the cells
      were cultured in medium containing PD98059 (ERK1/2 inhibitor) or were transfected
      with siRNAs against MEK1 or ELK-1. Overexpression of apo(a) yielded similar
      results. CONCLUSIONS: This study reveals that DADS can downregulate apo(a)
      expression in a dose-dependent manner via the MEK-ERK12-ELK-1 pathway.

PMID- 29178938
TI  - Iatrogenic hemodilution: a possible cause for avoidable blood transfusions?

PMID- 29178937
TI  - An optimized background regimen design to evaluate the contribution of
      levofloxacin to multidrug-resistant tuberculosis treatment regimens: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Current guidelines for treatment of multidrug-resistant tuberculosis
      (MDR-TB) are largely based on expert opinion and observational data.
      Fluoroquinolones remain an essential part of MDR-TB treatment, but the optimal
      dose of fluoroquinolones as part of the regimen has not been defined.
      METHODS/DESIGN: We designed a randomized, blinded, phase II trial in MDR-TB
      patients comparing across levofloxacin doses of 11, 14, 17 and 20 mg/kg/day, all
      within an optimized background regimen. We assess pharmacokinetics, efficacy,
      safety and tolerability of regimens containing each of these doses. The primary
      efficacy outcome is time to culture conversion over the first 6 months of
      treatment. The study aims to determine the area under the curve (AUC) of the
      levofloxacin serum concentration in the 24 hours after dosing divided by the
      minimal inhibitory concentration of the patient's Mycobacterium tuberculosis
      isolate that inhibits > 90% of organisms (AUC/MIC) that maximizes efficacy and
      the AUC that maximizes safety and tolerability in the context of an MDR-TB
      treatment regimen. DISCUSSION: Fluoroquinolones are an integral part of
      recommended MDR-TB regimens. Little is known about how to optimize dosing for
      efficacy while maintaining acceptable toxicity. This study will provide evidence
      to support revised dosing guidelines for the use of levofloxacin as part of
      combination regimens for treatment of MDR-TB. The novel methodology can be
      adapted to elucidate the effect of other single agents in multidrug antibiotic
      treatment regimens. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01918397 .
      Registered on 5 August 2013.

PMID- 29178939
TI  - Autocrine parathyroid hormone-like hormone promotes intrahepatic
      cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1
      signaling.
AB  - BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is an aggressive tumor
      with a high fatality rate. It was recently found that parathyroid hormone-like
      hormone (PTHLH) was frequently overexpressed in ICC compared with non-tumor
      tissue. This study aimed to elucidate the underlying mechanisms of PTHLH in ICC
      development. METHODS: The CCK-8 assay, colony formation assays, flow cytometry
      and a xenograft model were used to examine the role of PTHLH in ICC cells
      proliferation. Immunohistochemistry (IHC) and western blot assays were used to
      detect target proteins. Luciferase reporter, chromatin immunoprecipitation (ChIP)
      and DNA pull-down assays were used to verify the transcription regulation of
      activating transcription factor-2 (ATF2). RESULTS: PTHLH was significantly
      upregulated in ICC compared with adjacent and normal tissues. Upregulation of
      PTHLH indicated a poor pathological differentiation and intrahepatic metastasis.
      Functional study demonstrated that PTHLH silencing markedly suppressed ICC cells
      growth, while specific overexpression of PTHLH has the opposite effect.
      Mechanistically, secreted PTHLH could promote ICC cell growth by activating
      extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK)
      signaling pathways, and subsequently upregulated ATF2 and cyclinD1 expression.
      Further study found that the promoter activity of PTHLH were negatively regulated
      by ATF2, indicating that a negative feedback loop exists. CONCLUSIONS: Our
      findings demonstrated that the ICC-secreted PTHLH plays a characteristic growth
      promoting role through activating the canonical ERK/JNK-ATF2-cyclinD1 signaling
      pathways in ICC development. We identified a negative feedback loop formed by
      ATF2 and PTHLH. In this study, we explored the therapeutic implication for ICC
      patients.

PMID- 29178940
TI  - Restoration of motor control and proprioceptive and cutaneous sensation in humans
      with prior upper-limb amputation via multiple Utah Slanted Electrode Arrays
      (USEAs) implanted in residual peripheral arm nerves.
AB  - BACKGROUND: Despite advances in sophisticated robotic hands, intuitive control of
      and sensory feedback from these prostheses has been limited to only 3-degrees-of
      freedom (DOF) with 2 sensory percepts in closed-loop control. A Utah Slanted
      Electrode Array (USEA) has been used in the past to provide up to 81 sensory
      percepts for human amputees. Here, we report on the advanced capabilities of
      multiple USEAs implanted in the residual peripheral arm nerves of human amputees
      for restoring control of 5 DOF and sensation of up to 131 proprioceptive and
      cutaneous hand sensory percepts. We also demonstrate that USEA-restored sensory
      percepts provide a useful source of feedback during closed-loop virtual
      prosthetic hand control. METHODS: Two 100-channel USEAs were implanted for 4-5
      weeks, one each in the median and ulnar arm nerves of two human subjects with
      prior long-duration upper-arm amputations. Intended finger and wrist positions
      were decoded from neuronal firing patterns via a modified Kalman filter, allowing
      subjects to control many movements of a virtual prosthetic hand. Additionally,
      USEA microstimulation was used to evoke numerous sensory percepts spanning the
      phantom hand. Closed-loop control was achieved by stimulating via an electrode of
      the ulnar-nerve USEA while recording and decoding movement via the median-nerve
      USEA. RESULTS: Subjects controlled up to 12 degrees-of-freedom during informal,
      'freeform' online movement decode sessions, and experienced up to 131 USEA-evoked
      proprioceptive and cutaneous sensations spanning the phantom hand. Independent
      control was achieved for a 5-DOF real-time decode that included flexion/extension
      of the thumb, index, middle, and ring fingers, and the wrist. Proportional
      control was achieved for a 4-DOF real-time decode. One subject used a USEA-evoked
      hand sensation as feedback to complete a 1-DOF closed-loop virtual-hand movement
      task. There were no observed long-term functional deficits due to the USEA
      implants. CONCLUSIONS: Implantation of high-channel-count USEAs enables multi
      degree-of-freedom control of virtual prosthetic hand movement and restoration of
      a rich selection of both proprioceptive and cutaneous sensory percepts spanning
      the hand during the short 4-5 week post-implant period. Future USEA use in longer
      term implants and in closed-loop may enable restoration of many of the
      capabilities of an intact hand while contributing to a meaningful embodiment of
      the prosthesis.

PMID- 29178941
TI  - S100A8/A9 and sRAGE kinetic after polytrauma; an explorative observational study.
AB  - BACKGROUND: Following tissue injury after trauma, the activation of innate immune
      pathways results in systemic inflammation, organ failure and an increased risk of
      infections. The objective of this study was to characterize the kinetics of the
      S100A8/S100A9 complex, a new-recognized alarmin, as well as its soluble receptor
      sRAGE, over time after trauma as potential early biomarkers of the risk of organ
      damage. METHODS: We collected comprehensive data from consenting patients
      admitted to an ICU following severe trauma. The blood samples were taken at Day 0
      (admission), Day1, 3 and 5 S100A8/A9 and sRAGE were measured by ELISA. Biomarkers
      levels were reported as median (IQR). RESULTS: Thirty-eight patients sustaining
      in majority a blunt trauma (89%) with a median ISS of 39 were included. In this
      cohort, the S100A8/A9 complex increased significantly over time (p = 0.001), but
      its levels increment over time (D0 to D5) was significantly smaller in patients
      developing infection (7.6 vs 40.1 mcg/mL, p = 0.011). The circulating level of
      sRAGE circulating levels decreased over time (p < 0.0001) and was higher in
      patients who remained in shock on day 3 (550 vs 918 pg/mL; p = 0.02) or 5 (498 vs
      644 pg/mL; p = 0.045). Admission sRAGE levels were significantly higher in non
      survivors (1694 vs 745 pg/mL; p = 0.015) and was higher in patients developing
      renal failure (1143 vs 696 pg/mL, p = 0.011). DISCUSSION: Our findings reveal an
      interesting association between the biomarker S100A8/9 least increase over time
      and the presence of infectious complication after trauma. We describe that the
      sRAGE decline over time is in relation with shock and markers of ischemic injury.
      We also confirm the association of sRAGE levels measured at admission with
      mortality and the development of renal failure. CONCLUSIONS: This work
      illustrates the importance of following the circulating level of biomarker
      overtime. The utilization of S1008/9 as a tool to stratify infection risk and
      trigger early interventions need to be validated prospectively.

PMID- 29178942
TI  - Antioxidant effect of aqueous extract of four plants with therapeutic potential
      on gynecological diseases; Semen persicae, Leonurus cardiaca, Hedyotis diffusa,
      and Curcuma zedoaria.
AB  - BACKGROUND: Little information is available concerning antioxidant effects of
      plant teas (water boiled) which are used more commonly in traditional Chinese
      medicine than other extracts. Thus, we addressed this issue by evaluating the
      ability of teas from four different plants with therapeutic potential on
      gynecological diseases. METHODS: The aqueous extracts of Semen persicae, Leonurus
      cardiaca, Hedyotis diffusa, and Curcuma zedoaria rhizome were prepared and then
      their effects on copper-induced low-density lipoprotein cholesterol (LDL-C)
      oxidation were evaluated by spectrophotometric method. Density gradient
      ultracentrifugation method was recruited to isolate LDL-C from healthy
      individuals. RESULTS: Our results showed that adding 10, 20, and 30 ul S.
      persicae could increase the lag phase duration of LDL-C oxidation compared with
      control reaction 12, 21, and 33%, respectively. The most effective delay (87%)
      was observed when 30 ul H. diffusa was added to the reaction. In cases of L.
      cardiaca and C. zedoaria, we found no significant influence on the lag phase
      duration (p > 0.05). Moreover, our findings about starting point of the
      decomposition phase were almost in parallel with the lag phase results, as 30 ul
      of S. persicae or H. diffusa teas could significantly increase the initiation
      time of decomposition (p < 0.05). CONCLUSIONS: In conclusion our results showed
      that both S. persicae and H. diffusa teas and not L. cardiaca and C. zedoaria
      could have medicinal therapeutic effects partly through direct oxidation
      prevention.

PMID- 29178944
TI  - Malignant acanthosis nigricans: an early diagnostic clue for gastric
      adenocarcinoma.
AB  - BACKGROUND: Malignant acanthosis nigricans (MAN), characterized by the presence
      of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous
      sign of internal malignancy. Few MAN has been reported in the Asian race ever
      before. CASE PRESENTATION: Here, we report a rare case of MAN with severe mucosa
      and soles and extraordinary facial involvement in the Asian race. A 74-year-old
      man presented with hyperkeratotic eruption for 7 months. Physical examination
      revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels,
      and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed
      hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The
      endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia
      tubular adenocarcinoma. The patient was diagnosed with MAN associated with
      gastric adenocarcinoma, immediately following tumor resection and
      lymphadenectomy. A slight improvement was seen in the skin condition but died of
      cancer cachexia 3 months later. CONCLUSIONS: We report our typical patient to
      highlight the importance of MAN, which was an early clue to the discovery of
      gastric adenocarcinoma.

PMID- 29178943
TI  - High-volume hemofiltration in adult burn patients with septic shock and acute
      kidney injury: a multicenter randomized controlled trial.
AB  - BACKGROUND: Sepsis and septic shock occur commonly in severe burns. Acute kidney
      injury (AKI) is also common and often results as a consequence of sepsis.
      Mortality is unacceptably high in burn patients who develop AKI requiring renal
      replacement therapy and is presumed to be even higher when combined with septic
      shock. We hypothesized that high-volume hemofiltration (HVHF) as a blood
      purification technique would be beneficial in this population. METHODS: We
      conducted a multicenter, prospective, randomized, controlled clinical trial to
      evaluate the impact of HVHF on the hemodynamic profile of burn patients with
      septic shock and AKI involving seven burn centers in the United States. Subjects
      randomized to the HVHF were prescribed a dose of 70 ml/kg/hour for 48 hours while
      control subjects were managed in standard fashion in accordance with local
      practices. RESULTS: During a 4-year period, a total of nine subjects were
      enrolled for the intervention during the ramp-in phase and 28 subjects were
      randomized, 14 each into the control and HVHF arms respectively. The study was
      terminated due to slow enrollment. Ramp-in subjects were included along with
      those randomized in the final analysis. Our primary endpoint, the vasopressor
      dependency index, decreased significantly at 48 hours compared to baseline in the
      HVHF group (p = 0.007) while it remained no different in the control arm. At 14
      days, the multiple organ dysfunction syndrome score decreased significantly in
      the HVHF group when compared to the day of treatment initiation (p = 0.02). No
      changes in inflammatory markers were detected during the 48-hour intervention
      period. No significant difference in survival was detected. No differences in
      adverse events were noted between the groups. CONCLUSIONS: HVHF was effective in
      reversing shock and improving organ function in burn patients with septic shock
      and AKI, and appears safe. Whether reversal of shock in these patients can
      improve survival is yet to be determined. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01213914 . Registered 30 September 2010.

PMID- 29178945
TI  - CRISPR/Cas9-mediated targeted chromosome elimination.
AB  - BACKGROUND: The CRISPR/Cas9 system has become an efficient gene editing method
      for generating cells carrying precise gene mutations, including the rearrangement
      and deletion of chromosomal segments. However, whether an entire chromosome could
      be eliminated by this technology is still unknown. RESULTS: Here we demonstrate
      the use of the CRISPR/Cas9 system to eliminate targeted chromosomes. Using either
      multiple cleavages induced by a single-guide RNA (sgRNA) that targets multiple
      chromosome-specific sites or a cocktail of multiple sgRNAs, each targeting one
      specific site, we found that a sex chromosome could be selectively eliminated in
      cultured cells, embryos, and tissues in vivo. Furthermore, this approach was able
      to produce a targeted autosome loss in aneuploid mouse embryonic stem cells with
      an extra human chromosome and human induced pluripotent stem cells with trisomy
      21, as well as cancer cells. CONCLUSIONS: CRISPR/Cas9-mediated targeted
      chromosome elimination offers a new approach to develop animal models with
      chromosome deletions, and a potential therapeutic strategy for human aneuploidy
      diseases involving additional chromosomes.

PMID- 29178947
TI  - Dangguijakyak-san ameliorates memory deficits in ovariectomized mice by
      upregulating hippocampal estrogen synthesis.
AB  - BACKGROUND: Dangguijakyak-san (DJS) is an herbal formulation that has been
      clinically applicable for treating postmenopausal symptoms and neurological
      disorders. It is reported that hippocampal estrogen attenuates memory impairment
      via neuroprotection and synaptogenesis. However, the effect of DJS on hippocampal
      estrogen synthesis remains unknown. In this study, we explored the effect of DJS
      and its neuroprotective mechanism against memory impairment in ovariectomized
      (OVX) mice, with respect to hippocampal estrogen stimulation. METHODS: Cell
      cultures were prepared from the hippocampi of 18-day-old embryos from timed
      pregnant Sprague-Dawley rats. The hippocampi were dissected, collected,
      dissociated, and plated in 60-mm dishes. The cells were treated with DJS for 48 h
      and the supernatant was collected to determine estrogen levels. Female ICR mice
      (8-weeks-old) were housed for 1 week and ovariectomy was performed to remove the
      influence of ovary-synthesized estrogens. Following a 2-week post-surgical
      recovery period, the mice were administrated with DJS (50 and 100 mg/kg/day,
      p.o.) or 17beta-estradiol (200 MUg/kg/day, i.p.) once daily for 21 days.
      Hippocampal and serum estrogen levels were determined using enzyme-linked
      immunosorbent assay kit. Memory behavioral tests, western blot, and
      immunohistochemical analyses were performed to evaluate the neuroprotective
      effects of DJS in this model. RESULTS: DJS treatment promoted estrogen synthesis
      in primary hippocampal cells and the hippocampus of OVX mice, resulting in the
      amelioration of OVX-induced memory impairment. Hippocampal estrogen stimulated by
      DJS treatment contributed to the activation of cAMP response element-binding
      protein and synaptic protein in OVX mice. CONCLUSION: DJS may attenuate memory
      deficits in postmenopausal women via hippocampal estrogen synthesis.

PMID- 29178946
TI  - A putative causal relationship between genetically determined female body shape
      and posttraumatic stress disorder.
AB  - BACKGROUND: The nature and underlying mechanisms of the observed increased
      vulnerability to posttraumatic stress disorder (PTSD) in women are unclear.
      METHODS: We investigated the genetic overlap of PTSD with anthropometric traits
      and reproductive behaviors and functions in women. The analysis was conducted
      using female-specific summary statistics from large genome-wide association
      studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and
      2611 trauma-exposed controls). We applied a high-resolution polygenic score
      approach and Mendelian randomization analysis to investigate genetic correlations
      and causal relationships. RESULTS: We observed an inverse association of PTSD
      with genetically determined anthropometric traits related to body shape,
      independent of body mass index (BMI). The top association was related to BMI
      adjusted waist circumference (WCadj; R = -0.079, P < 0.001, Q = 0.011). We
      estimated a relative decrease of 64.6% (95% confidence interval = 27.5-82.7) in
      the risk of PTSD per 1-SD increase in WCadj. MR-Egger regression intercept
      analysis showed no evidence of pleiotropic effects in this association
      (Ppleiotropy = 0.979). We also observed associations of genetically determined
      WCadj with age at first sexual intercourse and number of sexual partners (P =
      0.013 and P < 0.001, respectively). CONCLUSIONS: There is a putative causal
      relationship between genetically determined female body shape and PTSD, which
      could be mediated by evolutionary mechanisms involved in human sexual behaviors.

PMID- 29178948
TI  - MiR-139 suppresses beta-casein synthesis and proliferation in bovine mammary
      epithelial cells by targeting the GHR and IGF1R signaling pathways.
AB  - BACKGROUND: MicroRNAs have important roles in many biological processes. However,
      the role of miR-139 in healthy mammary gland remains unclear. The objective of
      this study was to investigate the effects of miR-139 on lactation in dairy cows.
      RESULTS: Here, we found that miR-139 was down-regulated in mid-lactation dairy
      cow mammary tissues compared with mid-pregnancy tissues. Then, we prioritized two
      of potential target genes of miR-139 in cow, growth hormone receptor (GHR) and
      type I insulin-like growth factor receptor (IGF1R) for further functional studies
      based on their roles in lactation processes. Dual luciferase reporter assays
      validated direct binding of miR-139 to the 3'- untranslated region (UTR) of GHR
      and IGF1R. Moreover, over-expression or silencing of miR-139 affected mRNA levels
      of GHR and IGF1R in cultured bovine mammary epithelial cells (BMECs).
      Furthermore, over-expression of miR-139 decreased protein levels of beta-casein,
      proliferation in mammary epithelial cell, and the protein levels of IGF1R and key
      members of the GHR or IGF1R pathways as well, whereas silencing miR-139 produced
      the opposite result. Among these signal molecules, signal transducer and
      activator of transcription-5 (STAT5), protein kinase B (also known as AKT1),
      mammalian target of rapamycin (mTOR), and p70-S6 Kinase (p70S6K) are involed in
      beta-casein synthesis, and Cyclin D1 is involved in cell proliferation. In
      addition, silencing GHR decreased protein levels of beta-casein, IGF1R, and key
      members of the IGF1R pathway, whereas co-silencing miR-139 and GHR rescued the
      expression of GHR and reversed GHR silencing effects. CONCLUSIONS: Our results
      demonstrate that GHR and IGF1R are target genes of miR-139 in dairy cow. MiR-139
      suppresses beta-casein synthesis and proliferation in BMECs by targeting the GHR
      and IGF1R signaling pathways.

PMID- 29178949
TI  - Valued experiences of graduate students in their role as educators in
      undergraduate training in Ugandan medical schools.
AB  - BACKGROUND: In most medical schools, graduate students, sometimes referred to as
      graduate teaching assistants, often participate in the training of undergraduate
      students. In developing countries like Uganda, are typically involved in
      undergraduate training. However, prior to this study there were no standard
      guidelines for this involvement. At the same time, the views and experiences of
      the graduate students in their role as educators had not been documented.
      Therefore, the aim of this study was to explore the views and experiences of
      graduate students about their involvement in undergraduate training in three
      Ugandan medical schools. The findings of this study will contribute to the
      development of policies for training in Ugandan medical schools. METHODS: This
      was a qualitative study in which thirty in-depth-interviews were conducted among
      second and third year graduate students in three Ugandan medical schools in the
      MESAU consortium (Medical Education Services to all Ugandans) including Mbarara
      University of Science and Technology, Makerere College of Health Sciences and
      Kampala International University, Western Campus. RESULTS: All graduate students
      from all the three medical schools viewed their involvement in undergraduate
      training as important. The study also revealed that graduate students increase
      available human resources and often compensate for the teaching missed when
      senior educators were absent. The graduate students expressed important views
      that need to be considered in the design of educational programs where they are
      to be involved. The respondents also reported a number of challenges in this
      undertaking that included lack of motivation, lack of orientation and having
      heavy workloads. The presence and commitment of senior educators to guide and
      support the graduate students in teaching activities was viewed as one
      significant intervention that would increase the effectiveness of their
      educational contributions. CONCLUSIONS: Graduate students enjoy their involvement
      in the training of undergraduate students despite the various challenges they
      face. In some departments, the involvement of postgraduate trainees is critical
      to the viability of undergraduate medical training.

PMID- 29178950
TI  - Declining rates of sterilisation reversal procedures in western Australian women
      from 1990 to 2008: the relationship with age, hospital type and government policy
      changes.
AB  - BACKGROUND: Female sterilisation is usually performed on an elective basis at
      perceived family completion, however, around 1-3% of women who have undergone
      sterilisation elect to undergo sterilisation reversal (SR) at a later stage. The
      trends in SR rates in Western Australia (WA), proportions of SR procedures
      between hospital types (public and private), and the effects of Federal
      Government policies on these trends are unknown. METHODS: Using records from
      statutory state-wide data collections of hospital separations and births, we
      conducted a retrospective descriptive study of all women aged 15-49 years who
      underwent a SR procedure during the period 1st January 1990 to 31st December 2008
      (n = 1868 procedures). RESULTS: From 1991 to 2007 the annual incidence rate of SR
      procedures per 10,000 women declined from 47.0 to 3.6. Logistic regression
      modelling showed that from 1997 to 2001 the odds of women undergoing SR in a
      private hospital as opposed to all other hospitals were 1.39 times higher (95% CI
      1.07-1.81) and 7.51 times higher (95% CI 5.46-10.31) from 2002 to 2008. There
      were significant decreases in SR rates overall and among different age groups
      after the Federal Government interventions. CONCLUSION: Rates of SR procedures in
      WA have declined from 1990 to 2008, particularly following policy changes such as
      the introduction of private health insurance (PHI) policies. This suggests
      decisions to undergo SR may be influenced by Federal Government interventions.

PMID- 29178951
TI  - African animal trypanosomiasis as a constraint to livestock health and production
      in Karamoja region: a detailed qualitative and quantitative assessment.
AB  - BACKGROUND: Nagana (African Animal Trypanosomiasis-AAT) and tick-borne diseases
      (TBDs) constrain livestock production in most parts of sub-Saharan Africa. To
      this realisation, Uganda government set up an African trypanosomiasis (AT)
      control unit, which among other activities generates national tsetse control
      priority maps using apparent tsetse density data. Such maps underestimate
      mechanically transmitted AAT and thus ought to be refined using actual AT
      prevalence data. We therefore set out to generate up-to-date cattle and donkey
      trypanosomiasis prevalence data as well as find out the constraints to livestock
      production in Karamoja region in a bid to re-define AT control priority in this
      region. RESULTS: Livestock keepers and animal health workers indicated that TBDs
      and AAT were the most important livestock diseases in Karamoja region. The
      prevalence of Trypanosoma spp. in cattle and donkeys was 16.3% (95% CI: 12.4
      21.1%) and 32.4% (95% CI; 20.2-47.6%) respectively. Trypanosoma vivax (12.1%) and
      Trypanosoma congolense savannah (29.6%) were the most prevalent Trypanosoma spp.
      in cattle and donkeys respectively. Majority of the cattle (85.7%) and more than
      half of the donkey (57.1%) herds were positive for Trypanosoma spp. CONCLUSIONS:
      African animal trypanosomiasis and TBDs are the most important constraints to
      livestock production in Karamoja region. In order to improve livestock production
      and hence Karamajong livelihoods, government of Uganda and her development
      partners will need to invest in livestock health programs particularly targeting
      tsetse and TBD control.

PMID- 29178952
TI  - Status of benzimidazole resistance in intestinal nematode populations of
      livestock in Brazil: a systematic review.
AB  - BACKGROUND: Benzimidazoles (BZ) are a class of drugs widely used in veterinary
      and human medicine, creating a great selection pressure and the emergence of BZ
      resistance. We conducted a systematic review to assess the status of resistance
      and/or effectiveness reduction of BZ drugs in animal nematodes in Brazil, and
      make information accessible to the scientific community, as many studies are
      published in Portuguese. PubMed, SciELO Brasil, LILACS/Bireme, GNTD database, and
      Google Scholar were searched with no language restrictions. RESULTS: A total of
      40 studies met our eligibility criteria (from the year 1989 forward). Sheep was
      the host most frequently analysed, and albendazole was the most frequently drug
      studied. The majority of studies (75.7%) showed that BZ drugs are insufficiently
      active (FECRT <80%) against nematode parasites of livestock. The mean FECRT for
      fenbendazole, thiabendazole, albendazole, mebendazole, oxfendazole, and
      ricobendazole were 71.8%, 71.8%, 58.6%, 53.9%, 46.9%, and 41.5%, respectively. It
      was observed through linear regression that FECRT is significantly reduced over
      time between 2007 and 2014 (R = -0.653 p = 0.021) for the treatment of cattle
      with BZ, suggesting progressive loss of effectiveness and increased resistance
      for these hosts. CONCLUSIONS: The scenario of BZ resistance in nematode
      populations in Brazil is not favourable. Given the high cost of drug discovery
      and development, it is urgent to implement control measures and to monitor the
      effectiveness/resistance to nematodes in livestock in Brazil.

PMID- 29178953
TI  - Video laryngoscopy does not improve the intubation outcomes in emergency and
      critical patients - a systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: There is significant controversy regarding the influence of video
      laryngoscopy on the intubation outcomes in emergency and critical patients. This
      systematic review and meta-analysis was designed to determine whether video
      laryngoscopy could improve the intubation outcomes in emergency and critical
      patients. METHODS: We searched the Cochrane Central Register of Controlled
      Trials, PubMed, Embase, and Scopus databases from database inception until 15
      February 2017. Only randomized controlled trials comparing video and direct
      laryngoscopy for tracheal intubation in emergency department, intensive care
      unit, and prehospital settings were selected. The primary outcome was the first
      attempt success rate. Review Manager 5.3 software was used to perform the pooled
      analysis and assess the risk of bias for each eligible study. The GRADE (Grading
      of Recommendations Assessment, Development and Evaluation) system was used to
      assess the quality of evidence for all outcomes. RESULTS: Twelve studies (2583
      patients) were included in the review for data extraction. Pooled analysis did
      not show an improved first-attempt success rate using video laryngoscopy
      (relative risk [RR], 0.93; P = 0.28; low-quality evidence). There was significant
      heterogeneity among studies (I 2 = 91%). Subgroup analyses showed that, in the
      prehospital setting, video laryngoscopy decreased the first-attempt success rate
      (RR, 0.57; P < 0.01; high-quality evidence) and overall success rate (RR, 0.58;
      95% CI, 0.48-0.69; moderate-quality evidence) by experienced operators, whereas
      in the in-hospital setting, no significant difference between two devices was
      identified for the first-attempt success rate (RR, 1.06; P = 0.14; moderate
      quality evidence), regardless of the experience of the operators or the types of
      video laryngoscopes used (P > 0.05), although a slightly higher overall success
      rate was shown (RR, 1.11; P = 0.03; moderate-quality evidence). There were no
      differences between devices for other outcomes (P > 0.05), except for a lower
      rate of esophageal intubation (P = 0.01) and a higher rate of Cormack and Lehane
      grade 1 (P < 0.01) when using video laryngoscopy. CONCLUSIONS: On the basis of
      the results of this study, we conclude that, compared with direct laryngoscopy,
      video laryngoscopy does not improve intubation outcomes in emergency and critical
      patients. Prehospital intubation is even worsened by use of video laryngoscopy
      when performed by experienced operators.

PMID- 29178954
TI  - The effectiveness of topical colloidal silver in recalcitrant chronic
      rhinosinusitis: a randomized crossover control trial.
AB  - BACKGROUND: Recalcitrant chronic rhinosinusitis without polyposis (CRSsP) is a
      challenging condition to manage as traditional medical therapies and surgery fail
      to provide satisfactory clinical improvements. Colloidal silver (CS), a widely
      used naturopathic agent, has recently shown anti-biofilm properties both in vitro
      and within a rhinosinusitis animal model. To date, no trials involving humans
      have been published in world literature. The purpose of this study was to assess
      the efficacy of CS as a topical nasal spray in patients with refractory CRSsP.
      METHODS: A prospective cohort study was conducted using a convenience sample of
      20 randomized patients with crossover methodology, comparing nasal sprays with CS
      versus saline. Patients sprayed twice daily for six weeks with the first
      intervention and then switched to the second for the next six weeks, with
      measurements made at baseline and each time point. Primary outcomes were changes
      in SNOT-22 and Lund-Kennedy (LK) endoscopic scores. All analysis was non
      parametric and was conducted using STATA 14. RESULTS: Twenty-two patients were
      enrolled in the study with 20 completing the entire protocol. Mean 6-week change
      in SNOT-22 scores were -2.8 and 1.0 for saline and CS, respectively (p = 0.373).
      Similarly, mean 6-week change in LK scores were -1.4 and -1.1 for saline and CS,
      respectively (p = 0.794). Significant period effects were observed with the SNOT
      22 score between the randomized groups. No participants experienced negative
      health effects directly attributable to the administration of intranasal CS.
      CONCLUSION: Commercially available CS nasal spray did not demonstrate any
      meaningful subjective or objective improvements in patients with recalcitrant
      CRSsP. TRIAL REGISTRATION: NCT02403479 . Registered on March 1, 2015.

PMID- 29178955
TI  - Cost evaluation, quality of life and pelvic organ function of three approaches to
      hysterectomy for benign uterine conditions: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Hysterectomy is the commonest major gynaecological surgery. Although
      there are many approaches to hysterectomy, which depend on clinical criteria,
      certain patients may be eligible to be operated in any of the several available
      approaches. However, most comparative studies on hysterectomy are between two
      approaches. There is also a relative absence of data on long-term outcomes on
      quality of life and pelvic organ function. There is no single study which has
      considered quality of life, pelvic organ function and cost-effectiveness for the
      three main types of hysterectomy. Therefore, the objective of this study is to
      provide evidence on the optimal route of hysterectomy in terms of cost
      effectiveness by way of a three-armed randomized control study between non
      descent vaginal hysterectomy, total laparoscopic hysterectomy and total abdominal
      hysterectomy. METHODS: A multicentre three-armed randomized control trial is
      being conducted at the professorial gynaecology unit of the North Colombo
      Teaching Hospital, Ragama, Sri Lanka and gynaecology unit of the District General
      Hospital, Mannar, Sri Lanka. The study population is women needing hysterectomy
      for non-malignant uterine causes. Patients with a uterus > 14 weeks, previous
      pelvic surgery, those requiring incontinence surgery or pelvic floor surgery, any
      medical illness which caution/contraindicate laparoscopic surgery and who cannot
      read and write will be excluded. The main exposure variable is non-descent
      vaginal hysterectomy and total laparoscopic hysterectomy. The control group will
      be patients undergoing total abdominal hysterectomy. The primary outcome is time
      to recover following surgery, which is the earliest time to resume all of the
      usual activities done prior to surgery. In total, 147 patients (49 per arm) are
      needed to have 80% power at alpha-0.01 considering a loss to follow-up of 20% to
      detect a 7-day difference between the three routes; TLH versus TAH versus NDVH.
      The economic evaluation will take a societal perspective and will include direct
      costs in relation to allocation of healthcare resources and indirect costs which
      are borne by the patient. A micro-costing approach will be adopted to calculate
      direct costs from the time of presentation to the gynaecology clinic up to 6
      months after surgery. Incremental cost-effectiveness ratios (ICER) will be
      obtained by calculating the incremental costs divided by the incremental effects
      (time to recover and QALYs gained) for the intervention groups (NDVH and TLH)
      over the standard care (TAH) group. DISCUSSION: The cost of the procedure,
      quality of life and pelvic organ function following the three main routes of
      hysterectomy are important to clinicians and healthcare providers, both in
      developed and developing countries. TRIAL REGISTRATION: The study was registered
      in the Sri Lanka clinical trials registry (SLCTR/2016/020) and the International
      Clinical Trials Registry Platform ( U1111-1194-8422 ) on 26 July 2016.

PMID- 29178956
TI  - Brucella seroprevalence in cattle near a wildlife reserve in Kenya.
AB  - OBJECTIVES: Brucellosis is caused by bacteria from the genus Brucella which
      infect human and domestic animals as well as wildlife. The Maasai Mara National
      Reserve has vast populations of wild ruminants such as buffaloes and wildebeest
      which could contribute to the risk of brucellosis in livestock, and the
      surrounding pastoralist communities grazing cattle in and around the reserve may
      be exposed to a higher risk of zoonotic diseases like brucellosis due to the
      close contact with livestock. In this study, cattle from three villages at
      varying distance from the reserve, were screened for antibodies against Brucella
      abortus. RESULTS: In total, 12.44% of 225 sampled animals were seropositive, with
      more females (15%) infected than males (5%). Seroprevalence was higher in
      livestock closer to Maasai Mara with the cattle in the village Mara Rianta having
      an odds ratio of 7.03 compared to Endoinyo Narasha further away (95% CI 1.4-11.1,
      p = 0.003), suggesting that a closer contact with wildlife may increase the
      circulation of infectious diseases between livestock and wildlife. Symptoms
      consistent with brucellosis were reported to occur in both humans and animals,
      and we thus conclude that brucellosis may be an important problem, both for the
      health and the economy.

PMID- 29178958
TI  - Gene expression of bovine embryos developing at the air-liquid interface on
      oviductal epithelial cells (ALI-BOEC).
AB  - We recently developed an air-liquid interface long-term culture of differentiated
      bovine oviductal epithelial cells (ALI-BOEC). This ex vivo oviduct epithelium is
      capable of supporting embryo development in co-culture up to the blastocyst stage
      without addition of embryo culture medium. However, blastocyst rates in co
      culture were markedly lower than in conventional in vitro embryo production
      procedures. In the present study, we assessed target gene expression of ALI-BOEC
      derived embryos to test their similarity to embryos from conventional in vitro
      embryo culture. We screened previously published data from developing bovine
      embryos and selected 41 genes which are either differentially expressed during
      embryo development, or reflect differences between various in vitro culture
      conditions or in vitro and in vivo embryos. Target gene expression was measured
      in 8-cell embryos and blastocysts using a 48.48 Dynamic ArrayTM on a Biomark HD
      instrument. For comparison with the ALI-BOEC system, we generated embryos by two
      different standard IVP protocols. The culture conditions lead to differential
      gene expression in both 8-cell embryos and blastocysts. Across the expression of
      all target genes the embryos developing on ALI-BOEC did not depart from
      conventional IVP embryos. These first results prove that gene expression in ALI
      BOEC embryos is not largely aberrant. However, there was no clear indication for
      a more in vivo-like target gene expression of these embryos. This calls for
      further optimization of the ALI-BOEC system to increase its efficiency both
      quantitatively and qualitatively.

PMID- 29178957
TI  - Triple combination antibiotic therapy for carbapenemase-producing Klebsiella
      pneumoniae: a systematic review.
AB  - BACKGROUND: The spread of carbapenemase-producing K. pneumoniae (CPKP) has become
      a significant problem worldwide. Combination therapy for CPKP is encouraging, but
      polymyxin resistance to many antibiotics is hampering effective treatment.
      Combination therapy with three or more antibiotics is being increasingly
      reported, therefore we performed a systematic review of triple combination cases
      in an effort to evaluate their clinical effectiveness for CPKP infections.
      METHODS: The PubMed database was searched to identify all published clinical
      outcomes of CPKP infections treated with triple combination therapy. Articles
      were stratified into two tiers depending on the level of clinical detail
      provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome,
      patient status at onset of infection, and source of infection. Articles not
      reaching these criteria were considered tier 2. RESULTS: Thirty-three studies
      were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were
      included in this analysis. The most common infection was pneumonia (31%) followed
      by primary or catheter-related bacteremia (21%) and urinary tract infection
      (17%). Different combinations of antibiotic classes were utilized in triple
      combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%),
      tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and
      microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients
      (52.4%), respectively. Overall mortality for patients treated with triple
      combination therapy was 35.8% (19/53 patients). CONCLUSIONS: Triple combination
      therapy is being considered as a treatment option for CPKP. Polymyxin-based
      therapy is the backbone antibiotic in these regimens, but its effectiveness needs
      establishing in prospective clinical trials.

PMID- 29178959
TI  - Sugar Lego: gene composition of bacterial carbohydrate metabolism genomic loci.
AB  - BACKGROUND: Bacterial carbohydrate metabolism is extremely diverse, since
      carbohydrates serve as a major energy source and are involved in a variety of
      cellular processes. Bacterial genes belonging to same metabolic pathway are often
      co-localized in the chromosome, but it is not a strict rule. Gene co-localization
      in linked to co-evolution and co-regulation. This study focuses on a large-scale
      analysis of bacterial genomic loci related to the carbohydrate metabolism.
      RESULTS: We demonstrate that only 53% of 148,000 studied genes from over six
      hundred bacterial genomes are co-localized in bacterial genomes with other
      carbohydrate metabolism genes, which points to a significant role of singleton
      genes. Co-localized genes form cassettes, ranging in size from two to fifteen
      genes. Two major factors influencing the cassette-forming tendency are gene
      function and bacterial phylogeny. We have obtained a comprehensive picture of co
      localization preferences of genes for nineteen major carbohydrate metabolism
      functional classes, over two hundred gene orthologous clusters, and thirty
      bacterial classes, and characterized the cassette variety in size and content
      among different species, highlighting a significant role of short cassettes. The
      preference towards co-localization of carbohydrate metabolism genes varies
      between 40 and 76% for bacterial taxa. Analysis of frequently co-localized genes
      yielded forty-five significant pairwise links between genes belonging to
      different functional classes. The number of such links per class range from zero
      to eight, demonstrating varying preferences of respective genes towards a
      specific chromosomal neighborhood. Genes from eleven functional classes tend to
      co-localize with genes from the same class, indicating an important role of
      clustering of genes with similar functions. At that, in most cases such co
      localization does not originate from local duplication events. CONCLUSIONS:
      Overall, we describe a complex web formed by evolutionary relationships of
      bacterial carbohydrate metabolism genes, manifested as co-localization patterns.
      REVIEWERS: This article was reviewed by Daria V. Dibrova (A.N. Belozersky
      Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow,
      Russia), nominated by Armen Mulkidjanian (University of Osnabruck, Germany), Igor
      Rogozin (NCBI, NLM, NIH, USA) and Yuri Wolf (NCBI, NLM, NIH, USA).

PMID- 29178960
TI  - The impact of a physician detailing and sampling program for generic
      atorvastatin: an interrupted time series analysis.
AB  - BACKGROUND: In 2011, Manitoba implemented a province-wide program of physician
      detailing and free sampling for generic atorvastatin to increase use of this
      generic statin. We examined the impact of this unique combined program of
      detailing and sampling for generic atorvastatin on the use and cost of statin
      medicines, market share of generic atorvastatin, the choice of starting statin
      for new users, and switching from a branded statin to generic atorvastatin.
      METHODS: We conducted a retrospective study of Manitoba insurance claims data for
      all continuously enrolled patients who filled one or more prescriptions for a
      statin between 2008 and 2013. Data were linked to physician-level data on the
      number of detailing visits and sample provision. We used interrupted time series
      analyses to assess policy-related changes in the use and cost of statin
      medicines, market share of generic atorvastatin, the choice of starting statin
      for new users, and switching from a branded statin to generic atorvastatin.
      RESULTS: The detailing program reached 31% (651/2103) of physicians who
      prescribed a statin during the study period. Collectively, these physicians
      prescribed 61% of statins dispensed in the province. Free sample cards were
      provided to 61% (394/651) of the detailed physicians. The program did not change
      the level or trend in the overall statin use rate and the total cost of statins
      or increase the number of patients switching from another branded statin to
      generic atorvastatin. We found the program had a small impact on atorvastatin's
      market share of new prescriptions, with a level increase of 2.6%. CONCLUSIONS:
      Though physician detailers were skilled at targeting high-prescribing physicians,
      a combined program of detailing visits and sample provision for generic
      atorvastatin did not lower overall statin costs or lead to switching from branded
      statins to the generic. The preceding introduction of generic atorvastatin
      appeared sufficient to modify prescribing patterns and decrease costs.

PMID- 29178962
TI  - Further psychometric validation of the BODY-Q: ability to detect change following
      bariatric surgery weight gain and loss.
AB  - BACKGROUND: Recent systematic reviews have identified that current patient
      reported outcome instruments have content limitations when used to measure change
      following bariatric surgery. The aim of this study was to measure change after
      bariatric surgery using the BODY-Q, a PRO instrument designed for weight loss and
      body contouring. METHODS: The BODY-Q is composed of 18 independently functioning
      scales and an obesity-specific symptom checklist that measure appearance, health
      related quality of life (HR-QOL) and experience of health-care. The sample for
      this study included patients who were exploring or seeking bariatric surgery in
      Hamilton (Canada) at the time of the BODY-Q field-test study and who agreed to
      further contact from the research team. These patients were invited to complete
      12 BODY-Q scales and the symptom checklist between 7 June 2016 and 29 November
      2016. Data were collected online (REDCap) and via postal surveys. Clinical change
      was measured using paired t-tests with effect sizes and standardized response
      means. RESULTS: The survey was completed by 58 of 89 (65%) pre-bariatric
      participants from the original BODY-Q field-test sample. The non-participants did
      not differ from participants in terms of age, gender, ethnicity, BMI or initial
      BODY-Q scale scores. Participants who had undergone bariatric surgery had a mean
      BMI of 49 (SD = 7) at time 1 and 35 (SD = 7) at time 2. Time since bariatric
      surgery was on average 2 years (SD = 0.5) (range 0.4 to 3 years). Percentage
      total weight loss ranged from 12 to 51 (mean 31, SD = 9). The difference in the
      proportion of patients to report an obesity-specific symptom on the BODY-Q
      checklist was significantly lower at follow-up for 5 of 10 symptoms. Participants
      improved on BODY-Q scales measuring appearance (of abdomen, back, body, buttocks,
      hips/outer thighs, inner thigh), body image and physical function (p < 0.001 on
      paired t-tests) and social function (p = 0.002 on paired t-test). These changes
      were associated with moderate to large effect sizes (0.60 to 2.29) and
      standardized response means (0.47 to 1.35). CONCLUSIONS: The BODY-Q provides a
      set of independently functioning scales that measure issues important to patients
      who undergo weight loss. BODY-Q scales were responsive to measuring clinical
      change associated with weight loss 2 years after bariatric surgery.

PMID- 29178963
TI  - Chloral hydrate enteral infusion for sedation in ventilated children: the CHOSEN
      pilot study.
AB  - BACKGROUND: We aimed to test a novel method of delivery of chloral hydrate (CH)
      sedation in ventilated critically ill young children. METHODS: Children < 12
      years old, within 72 hours of admission, who were ventilated, receiving enteral
      tube-feeds, with intermittent CH ordered were enrolled after signed consent.
      Patients received a CH loading-dose of 10 mg/kg enterally, then a syringe-pump
      enteral infusion at 5 mg/kg/hour, increasing to a maximum of 9 mg/kg/hour. Cases
      were compared to historical controls matched for age group and Pediatric Risk of
      Mortality score (PRISM) category, using Fisher's exact test and the t test. The
      primary outcome was feasibility, defined as the use of an enteral CH continuous
      infusion without discontinuation attributable to a pre-specified potential harm.
      RESULTS: There were 21 patients enrolled, at age 11.4 (12.1) months, with
      bronchiolitis in 10 (48%), a mean Pediatric Logistic Organ Dysfunction (PELOD)
      score of 6.2 (5.2), and having received enteral CH continuous infusion for 4.5
      (2.2) days. Infusion of CH was feasible in 20/21 (95%; 95% CI 76-99%) patients,
      with one (5%) adverse event of duodenal ulcer perforation on day 3 in a patient
      with croup receiving regular ibuprofen and dexamethasone. The CH infusion dose
      (mg/kg/h) on day 2 (n = 20) was 8.9 (IQR 5.9, 9), and on day 4 (n = 11) was 8.8
      (IQR 7, 9). Days to titration of adequate sedation (defined as <= 3 PRN
      doses/shift) was 1 (IQR 0.5, 2.5), and hours to awakening for extubation was 5
      (IQR 2, 9). Cases (versus controls) had less positive fluid balance at 48 h (-2
      (45) vs. 26 (46) ml/kg, p = 0.051), and a decrease in number of PRN sedation
      doses from 12 h pre to 12 hours post starting CH (4.7 (3.3) to 2.6 (2.8), p =
      0.009 versus 2.9 (3.9) to 3.4 (5), p = 0.74). There were no statistically
      significant differences between cases and controls in inotrope scores, signs or
      treatment of withdrawal, or PICU days. CONCLUSIONS: Delivering CH by continuous
      enteral infusion is feasible, effective, and may be associated with less positive
      fluid balance. Whether there is a risk of duodenal perforation requires further
      study.

PMID- 29178961
TI  - The unrecognized occupational relevance of the interaction between engineered
      nanomaterials and the gastro-intestinal tract: a consensus paper from a
      multidisciplinary working group.
AB  - BACKGROUND: There is a fundamental gap of knowledge on the health effects caused
      by the interaction of engineered nanomaterials (ENM) with the gastro-intestinal
      tract (GIT). This is partly due to the incomplete knowledge of the complex
      physical and chemical transformations that ENM undergo in the GIT, and partly to
      the widespread belief that GIT health effects of ENM are much less relevant than
      pulmonary effects. However, recent experimental findings, considering the role of
      new players in gut physiology (e.g. the microbiota), shed light on several
      outcomes of the interaction ENM/GIT. Along with this new information, there is
      growing direct and indirect evidence that not only ingested ENM, but also inhaled
      ENM may impact on the GIT. This fact, which may have relevant implications in
      occupational setting, has never been taken into consideration. This review paper
      summarizes the opinions and findings of a multidisciplinary team of experts,
      focusing on two main aspects of the issue: 1) ENM interactions within the GIT and
      their possible consequences, and 2) relevance of gastro-intestinal effects of
      inhaled ENMs. Under point 1, we analyzed how luminal gut-constituents, including
      mucus, may influence the adherence of ENM to cell surfaces in a size-dependent
      manner, and how intestinal permeability may be affected by different physico
      chemical characteristics of ENM. Cytotoxic, oxidative, genotoxic and inflammatory
      effects on different GIT cells, as well as effects on microbiota, are also
      discussed. Concerning point 2, recent studies highlight the relevance of gastro
      intestinal handling of inhaled ENM, showing significant excretion with feces of
      inhaled ENM and supporting the hypothesis that GIT should be considered an
      important target of extrapulmonary effects of inhaled ENM. CONCLUSIONS: In spite
      of recent insights on the relevance of the GIT as a target for toxic effects of
      nanoparticles, there is still a major gap in knowledge regarding the impact of
      the direct versus indirect oral exposure. This fact probably applies also to
      larger particles and dictates careful consideration in workers, who carry the
      highest risk of exposure to particulate matter.

PMID- 29178964
TI  - Over-expression of miR-146b and its regulatory role in intestinal epithelial cell
      viability, proliferation, and apoptosis in piglets.
AB  - BACKGROUND: Weaning stress affects the small intestine of piglets. MiR-146b is
      differentially expressed in suckling and weaned piglets. In this study, we
      evaluated the effects of miR-146b on cell viability, proliferation, and apoptosis
      in IPEC-J2 cells. RESULTS: Transfection with miR-146b mimics successfully
      increased miR-146b levels by 1000* (P < 0.001). The over-expression of miR-146b
      significantly promoted the apoptosis (P < 0.01) of IPEC-J2 cells, with no
      significant effects on cell viability or proliferation. MiR-146b suppressed the
      luciferase activity of the miR-TLR4-wt by 57% compared with the negative control,
      while mutation of the miR-146b binding site significantly blocked the suppressive
      effect (P < 0.05). Western blot results showed that TLR4 levels decreased in IPEC
      J2 cells transfected with miR-146b mimics (P < 0.05). CONCLUSIONS: The over
      expression of miR-146b promotes IPEC-J2 cell apoptosis. TLR4 is a direct target
      of miR-146b in IPEC-J2 cells. REVIEWERS: This article was reviewed by Eugene
      Berezikov and Jan B Hoek.

PMID- 29178965
TI  - A child with distal (type 1) renal tubular acidosis presenting with progressive
      gross motor developmental regression and acute paralysis.
AB  - BACKGROUND: Distal (Type 1) renal tubular acidosis (dRTA) is characterized by
      inability to secrete hydrogen irons from the distal tubule. The aetiology of dRTA
      is diverse and can be either inherited or acquired. Common clinical presentations
      of dRTA in the paediatric age group include polyuria, nocturia, failure to
      thrive, constipation, abnormal breathing and nephrolithiasis. Though persistent
      hypokalemia is frequently seen in dRTA, hypokalemic muscular paralysis is
      uncommon and rarely described in children. CASE PRESENTATION: Three and a half
      years old girl was referred for evaluation of progressive loss of gross motor
      milestones over 6 months and acute episode of paralysis. Her other developmental
      domains were age appropriate. Notably, there was no history of polyuria,
      polydipsia, nocturia and abnormal breathing. Physical examination revealed
      proximal myopathy (waddling gait and positive Gower's sign), diminished lower
      limb reflexes and muscle tone. Her serum potassium was low (2.1 meq/l) and she
      was subsequently investigated for hypokalemic paralysis. Diagnosis of distal
      renal tubular acidosis was made, based on hypokalemic hyperchloremic metabolic
      acidosis with normal anion gap, high urine pH, borderline hypercalciuria,
      medullary nephrocalcinosis and exclusion of other differential diagnosis. The
      child showed complete symptomatic recovery upon commencement of standard
      treatment for distal renal tubular acidosis. CONCLUSIONS: This case report
      highlights the importance of considering hypokalemia and renal tubular acidosis
      in the differential diagnosis of acute flaccid paralysis and proximal myopathy.
      Early diagnosis will prevent costly investigations and enable rapid clinical
      recovery in the affected child.

PMID- 29178966
TI  - Automated growth rate determination in high-throughput microbioreactor systems.
AB  - OBJECTIVE: The calculation of growth rates provides basic metric for biological
      fitness and is standard task when using microbioreactors (MBRs) in microbial
      phenotyping. MBRs easily produce huge data at high frequency from parallelized
      high-throughput cultivations with online monitoring of biomass formation at high
      temporal resolution. Resulting high-density data need to be processed efficiently
      to accelerate experimental throughput. RESULTS: A MATLAB code is presented that
      detects the exponential growth phase from multiple microbial cultivations in an
      iterative procedure based on several criteria, according to the model of
      exponential growth. These were obtained with Corynebacterium glutamicum showing
      single exponential growth phase and Escherichia coli exhibiting diauxic growth
      with exponential phase followed by retarded growth. The procedure reproducibly
      detects the correct biomass data subset for growth rate calculation. The
      procedure was applied on data set detached from growth phenotyping of library of
      genome reduced C. glutamicum strains and results agree with previously reported
      results where manual effort was needed to pre-process the data. Thus, the
      automated and standardized method enables a fair comparison of strain mutants for
      biological fitness evaluation. The code is easily parallelized and greatly
      facilitates experimental throughout in biological fitness testing from strain
      screenings conducted with MBR systems.

PMID- 29178969
TI  - A Rare Cause of Recurrent Constipation With Abdominal Pain and Distension.

PMID- 29178970
TI  - Reply.

PMID- 29178968
TI  - Cohort-specific imputation of gene expression improves prediction of warfarin
      dose for African Americans.
AB  - BACKGROUND: Genome-wide association studies are useful for discovering genotype
      phenotype associations but are limited because they require large cohorts to
      identify a signal, which can be population-specific. Mapping genetic variation to
      genes improves power and allows the effects of both protein-coding variation as
      well as variation in expression to be combined into "gene level" effects.
      METHODS: Previous work has shown that warfarin dose can be predicted using
      information from genetic variation that affects protein-coding regions. Here, we
      introduce a method that improves dose prediction by integrating tissue-specific
      gene expression. In particular, we use drug pathways and expression quantitative
      trait loci knowledge to impute gene expression-on the assumption that
      differential expression of key pathway genes may impact dose requirement. We
      focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of
      warfarin within training and validation sets comprising both European and African
      descent individuals. RESULTS: We build gene-tissue signatures associated with
      warfarin dose in a cohort-specific manner and identify a signature of 11 gene
      tissue pairs that significantly augments the International Warfarin
      Pharmacogenetics Consortium dosage-prediction algorithm in both populations.
      CONCLUSIONS: Our results demonstrate that imputed expression can improve dose
      prediction and bridge population-specific compositions. MATLAB code is available
      at https://github.com/assafgo/warfarin-cohort.

PMID- 29178967
TI  - Blocking ATP-sensitive potassium channel alleviates morphine tolerance by
      inhibiting HSP70-TLR4-NLRP3-mediated neuroinflammation.
AB  - BACKGROUND: Long-term use of morphine induces analgesic tolerance, which limits
      its clinical efficacy. Evidence indicated morphine-evoked neuroinflammation
      mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3)
      inflammasome was important for morphine tolerance. In our study, we investigated
      whether other existing alternative pathways caused morphine-induced activation of
      TLR4 in microglia. We focused on heat shock protein 70 (HSP70), a damage
      associated molecular pattern (DAMP), which was released from various cells upon
      stimulations under the control of KATP channel and bound with TLR4-inducing
      inflammation. Glibenclamide, a classic KATP channel blocker, can improve
      neuroinflammation by inhibiting the activation of NLRP3 inflammasome. Our present
      study investigated the effect and possible mechanism of glibenclamide in
      improving morphine tolerance via its specific inhibition on the release of HSP70
      and activation of NLRP3 inflammasome induced by morphine. METHODS: CD-1 mice were
      used for tail-flick test to evaluate morphine tolerance. The microglial cell line
      BV-2 and neural cell line SH-SY5Y were used to investigate the pharmacological
      effects and the mechanism of glibenclamide on morphine-induced neuroinflammation.
      The activation of microglia was accessed by immunofluorescence staining.
      Neuroinflammation-related cytokines were measured by western blot and real-time
      PCR. The level of HSP70 and related signaling pathway were evaluated by western
      blot and immunofluorescence staining. RESULTS: Morphine induced the release of
      HSP70 from neurons. The released HSP70 activated microglia and triggered TLR4
      mediated inflammatory response, leading to the phosphorylation of p38 mitogen
      activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) p65 and the
      activation of NLRP3 inflammasome. Moreover, anti-HSP70 neutralizing antibody
      partly attenuated chronic morphine tolerance. The secretion of HSP70 was under
      the control of MOR/AKT/KATP/ERK signal pathway. Glibenclamide as a classic KATP
      channel blocker markedly inhibited the release of HSP70 induced by morphine and
      suppressed HSP70-TLR4-NLRP3 inflammasome-mediated neuroinflammation, which
      consequently attenuated morphine tolerance. CONCLUSIONS: Our study indicated that
      morphine-induced extracellular HSP70 was an alternative way for the activation of
      TLR4-NLRP3 in analgesic tolerance. The release of HSP70 was regulated by
      MOR/AKT/KATP/ERK pathway. Our study suggested a promising target, KATP channel
      and a new leading compound, glibenclamide, for treating morphine tolerance.

PMID- 29178971
TI  - A 41-Year-Old Man With Abdominal Pain, Deranged Liver Function, and Fevers.

PMID- 29178972
TI  - A Rare Case of Epigastric Pain and Vomiting.

PMID- 29178973
TI  - An Usual Cause of Massive Upper Gastrointestinal Bleeding.

PMID- 29178974
TI  - Gastrocolic Fistula: A Rare Presentation of a Common Disease.

PMID- 29178975
TI  - A Rare Cause of Cecal Fistula.

PMID- 29178977
TI  - Evaluating test-retest reliability in patient-reported outcome measures for older
      people: A systematic review.
AB  - OBJECTIVES: This study aimed to evaluate the components of test-retest
      reliability including time interval, sample size, and statistical methods used in
      patient-reported outcome measures in older people and to provide suggestions on
      the methodology for calculating test-retest reliability for patient-reported
      outcomes in older people. DESIGN: This was a systematic literature review. DATA
      SOURCES: MEDLINE, Embase, CINAHL, and PsycINFO were searched from January 1, 2000
      to August 10, 2017 by an information specialist. REVIEW METHODS: This systematic
      review was guided by both the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses checklist and the guideline for systematic review published by
      the National Evidence-based Healthcare Collaborating Agency in Korea. The
      methodological quality was assessed by the Consensus-based Standards for the
      selection of health Measurement Instruments checklist box B. RESULTS: Ninety-five
      out of 12,641 studies were selected for the analysis. The median time interval
      for test-retest reliability was 14days, and the ratio of sample size for test
      retest reliability to the number of items in each measure ranged from 1:1 to 1:4.
      The most frequently used statistical methods for continuous scores was intraclass
      correlation coefficients (ICCs). Among the 63 studies that used ICCs, 21 studies
      presented models for ICC calculations and 30 studies reported 95% confidence
      intervals of the ICCs. Additional analyses using 17 studies that reported a
      strong ICC (>0.09) showed that the mean time interval was 12.88days and the mean
      ratio of the number of items to sample size was 1:5.37. CONCLUSIONS: When
      researchers plan to assess the test-retest reliability of patient-reported
      outcome measures for older people, they need to consider an adequate time
      interval of approximately 13days and the sample size of about 5 times the number
      of items. Particularly, statistical methods should not only be selected based on
      the types of scores of the patient-reported outcome measures, but should also be
      described clearly in the studies that report the results of test-retest
      reliability.

PMID- 29178976
TI  - How long should local warming for venodilation be used for peripheral intravenous
      cannulation? A prospective observational study.
AB  - BACKGROUND: Local warming is one of the most common venodilation techniques for
      achieving peripheral intravenous cannulation, but the time of application is
      unclear. OBJECTIVE: To compare the effectiveness of local warming applied for 5,
      10, and 15min. DESIGN: A prospective, observational study. SETTING: A university
      in Japan. PARTICIPANTS: In total, 40 healthy female volunteers aged 20-45 years
      were recruited via e-mail. METHODS: Participants received 15min of local warming
      with a warmed heat pack (40+/-2 degrees C). The primary outcome was the cross
      sectional area of the target vein at 5, 10, and 15min of warming, which was
      measured after the intervention by blinded review using ultrasound. Secondary
      outcomes included forearm target site temperature at 5, 10, and 15min of local
      warming, which was measured with a temperature sensor and handheld thermometer.
      RESULTS: Compared to outcomes before local warming, vein cross-sectional area at
      5, 10, and 15min of warming significantly (p <0.001) increased by 2.8, 2.9, and
      2.3mm2. The target site temperature increased by 6.9 degrees C, 6.4 degrees C,
      and 6.0 degrees C, respectively. However, no significant differences were found
      in cross-sectional area among the time points of 5, 10, and 15min of local
      warming. The target site temperature at 15min of local warming was significantly
      (p < 0.001) different than that at 5 and 10min. No adverse events occurred with
      local warming. CONCLUSION: Compared with outcomes before local warming, vein size
      after warming for 5, 10, and 15min was significantly larger. No significant
      differences were found in vein size among the time points of 5, 10, and 15min of
      local warming. Our result demonstrated the effectiveness of shorter-duration
      (5min) local warming for inducing venodilation for peripheral intravenous
      cannulation.

PMID- 29178978
TI  - The association between exposure to air pollutants including PM10, PM2.5, ozone,
      carbon monoxide, sulfur dioxide, and nitrogen dioxide concentration and the
      relative risk of developing STEMI: A case-crossover design.
AB  - BACKGROUND: Unfavorable associations between air pollution and myocardial
      infarction are broadly investigated in recent studies and some of them revealed
      considerable associations; however, controversies exists between these
      investigations with regard to culprit components of air pollution and
      significance of correlation between myocardial infarction risk and air pollution.
      METHODS: The association between exposure to PM10, PM2.5, ozone, carbon monoxide,
      sulfur dioxide, and nitrogen dioxide concentration of background air that
      residents of Tehran, the capital city of Iran, which is ranked as the most air
      polluted city of Iran and the relative risk of developing ST-elevation myocardial
      infarction (STEMI) were investigated by a case-crossover design. Our study
      included 208 patients admitted with a diagnosis of STEMI and undergone primary
      percutaneous intervention. Air pollutant concentration was averaged in 24-h
      windows preceding the time of onset of myocardial infarction for the case period.
      Besides, the mean level of each element of air pollution of the corresponding
      time in one week, two weeks and three weeks before onset of myocardial
      infarction, was averaged separately for each day as one control periods. Thus,
      624 control periods were included in our investigation such that. Each patient is
      matched and compared with him/herself. RESULTS: The mean level of PM10 in case
      periods (61.47ug/m3) was significantly higher than its level in control periods
      (57.86ug/m3) (P-value = 0.019, 95% CI: 1.002-1.018, RR = 1.010). Also, the mean
      level of PM2.5 in case periods (95.40ug/m3) was significantly higher than that in
      control days (90.88ug/m3) (P-value = 0.044, 95% CI: 1.001-1.011, RR = 1.006). The
      level of other components including NO2, SO2, CO and O3 showed no significant
      differences between case and control periods. A 10ug/m3 increase in PM10 and
      PM2.5 would result in 10.10% and 10.06% increase in STEMI event, respectively.
      Furthermore, the results of sub-group analysis showed that older patients (equal
      or more than 60 year-old), diabetic patients, non-hypertensive ones and patients
      with more than one diseased vessel may be more vulnerable to the harmful effect
      of particular matters including PM10 and PM2.5 on development of STEMI.
      CONCLUSION: Air pollution is a worldwide pandemic with great potential to cause
      terrible events especially cardiovascular ones. PM2.5 and PM10 are amongst
      ambient air pollutant with a high risk of developing STEMI. Thus, more
      restrictive legislations should be applied to define a safe level of indoor and
      outdoor air pollutant production.

PMID- 29178980
TI  - Ambient ultrafine particles activate human monocytes: Effect of dose,
      differentiation state and age of donors.
AB  - Exposure to ambient particulate matter (PM) has been linked to adverse pulmonary
      and cardiovascular health effects. Activation of both inflammatory and oxidative
      stress pathways has been observed and may be a probable cause of these outcomes.
      We tested the hypothesis that in human monocytes, PM-induced oxidative and
      inflammatory responses are interrelated. A human monocytic cell line (THP-1) was
      used to determine if dose and differentiation state plays a role in the cellular
      response after a 24hr exposure to particles. Primary human monocytes derived from
      eight female, non-smoker donors (aged: 21, 24, 27, 28, 48, 49, 54 & 60yo) were
      used to determine if the age of donors modulates the response. Cells were treated
      with aqueous suspensions of ambient ultrafine particles (UFP, defined as smaller
      than 0.2um in size) or a media control for 24hr. After exposure, reactive oxygen
      species (ROS) formation was increased irrespective of dose or differentiation
      state of THP-1 cells. In the primary human monocytes, ROS formation was not
      significantly changed. The release of the proinflammatory cytokine, tumor
      necrosis factor alpha (TNF-alpha), was dose-dependent and greatest in
      differentiated compared to undifferentiated THP-1 cells exposed to UFP. In the
      Primary human monocytes, TNF-alpha secretion was increased irrespective of the
      age of the donor. Our results suggest that after a 24hr exposure to particles,
      general reactive oxygen species formation was nonspecific and uncorrelated to
      cytokine secretion which was consistently enhanced. Cytokines play an important
      role in orchestrating many immune responses and thus the ability of ambient
      particles to enhance robust secretion of a proinflammatory cytokine from primary
      human monocytes, and how this may influence the response to pathogens and alter
      disease states, needs to be further evaluated.

PMID- 29178979
TI  - Unique pulmonary immunotoxicological effects of urban PM are not recapitulated
      solely by carbon black, diesel exhaust or coal fly ash.
AB  - BACKGROUND: Exposure to particulate matter (PM) is increasing worldwide as a
      result of increased human activity, the rapid industrialization of developing
      countries, and effects of climate change. Adverse effects of PM on human health
      are well documented, and because PM exposure occurs mostly through the airways,
      PM has especially deleterious impact on the lungs. OBJECTIVE: We investigated
      whether surrogate PM particles like carbon black (CB), diesel exhaust particle
      (DEP), coal fly ash (CFA) can recapitulate the allergic airway inflammatory
      response induced by urban particulate matter. METHODS: We compared the pro
      inflammatory potential of urban PM collected from New York (NYC) and Baltimore
      (Balt) with CB, DEP and CFA surrogate PM particles. Eight to ten weeks old
      BALB/cJ mice were exposed through the airways to particulate material, and
      markers of airway inflammation were determined. Specifically, we assessed
      cellular influx, mucus production, lung function, cytokine levels as well as
      immune cell profiling of the lungs. RESULTS: Herein, we demonstrate that exposure
      to equivalent mass of stand-alone surrogate PM particles like CB, DEP and CFA,
      fails to induce significant airway inflammatory response seen after similar
      exposure to urban PMs. Specifically, we observe that PM collected from New York
      (NYC) and Baltimore city (Balt) triggers a mixed Th2/Th17 response accompanied by
      eosinophilic and neutrophilic influx, mucus production and airway
      hyperresponsiveness (AHR). Although the immune profile of NYC and Baltimore PMs
      are similar, they demonstrate considerable differences in their potency.
      Baltimore PM induced more robust airway inflammation, AHR, and Th2 cytokine
      production, possibly due to the greater metal content in Baltimore PM.
      CONCLUSIONS: Urban particulate matter with its unique physiochemical properties
      and heterogeneous composition elicits a mixed Th2/Th17 allergic airway response
      that is not seen after similar exposures to surrogate PM particles.

PMID- 29178981
TI  - Translating Computer-Aided Design and Surgical Planning Into Successful
      Mandibular Reconstruction Using a Vascularized Iliac-Crest Flap.
AB  - PURPOSE: This study evaluated the computer-aided approach to the reconstruction
      of mandibular defects using a vascularized iliac-crest flap. MATERIALS AND
      METHODS: From December 2015 to October 2016, 14 patients (8 men and 6 women) 18
      to 64 years old (median age, 29 yr) were treated at the Peking University School
      and Stomatology Hospital (Beijing, China). Biopsy specimens from all patients
      were subjected to histologic examination before segmental mandibulectomy.
      Computer-based surgical techniques, including virtual surgical planning, computer
      aided design and manufacturing, rapid prototyping, and intraoperative navigation,
      were used to restore the anatomic continuity and configuration of the mandible
      using a vascularized iliac-crest flap. Two transverse dimensions and 1
      anteroposterior (A-P) dimension were evaluated based on the virtual plan and
      postoperative computed tomogram. Lines from condylar head to condylar head and
      from gonial angle to gonial angle were defined as the transverse dimensions. A
      perpendicular line drawn from the mandibular midline to the center point on the
      condylar head to condylar head measurement was defined as the A-P dimension.
      Complications were evaluated during follow-up. RESULTS: The flap success rate was
      92.9% (13 of 14), with 1 flap failure. After the operation, there were no other
      serious complications in 13 of the 14 patients, who exhibited a good mandibular
      configuration with good occlusion. Furthermore, the height of bone graft was
      sufficient for implants. Healing of the recipient and donor sites with no serious
      complication was uneventful. The average surgical errors in the A-P dimension and
      transverse dimensions were 1.8 +/- 1.0 mm (range, 0.2 to 3.7 mm), 2.2 +/- 1.1 mm
      (range, 0.9 to 5.0 mm), and 2.6 +/- 1.6 mm (range, 0.3 to 7.2 mm), respectively.
      CONCLUSIONS: The use of these digital techniques was found to be a viable option
      for reconstruction of mandibular defects, but the results should be interpreted
      cautiously because of the small number of patients and the relatively short
      follow-up.

PMID- 29178982
TI  - Microbiology Alloplastic Total Joint Infections: A 20-Year Retrospective Study.
AB  - PURPOSE: Prosthetic joint infection (PJI) is a rare complication of
      temporomandibular joint replacement (TJR). This study evaluated TJR PJIs at the
      authors' institution over a 20-year period, including micro-organisms cultured,
      antibiotic resistance patterns, and intraoperative protocols of TJR. PATIENTS AND
      METHODS: Patients were identified using Current Procedural Terminology and
      International Classification of Diseases, Ninth Revision codes and surgical logs
      from January 1995 through 2015. Inclusion criteria were adults older than 18
      years with previous alloplastic TJR and the presence of infection of the
      prosthesis at explantation. Exclusion criteria were patients younger than 18
      years and who received hemiarthroplasty. Primary outcomes included culture data
      and antibiotic selection for PJI. Secondary outcomes included intraoperative
      duration and in vivo duration. RESULTS: Eleven patients were identified and 15
      joints were explanted. Average length in vivo was 232 months (standard deviation,
      478.9 months). Six percent (n = 1) were identified as early PJI (0 to 3 months),
      46% (n = 7) were intermediate PJI (3 months to 2 yr), and 33% (n = 5) were late
      PJI (>2 yr). One patient could not be classified as early, intermediate, or late.
      Staphylococcus aureus was present in 53% of patients and was the predominant
      organism isolated. Propionibacterium acnes was isolated in 33% of patients.
      Penicillin was the antibiotic with the greatest organism resistance (46%).
      CONCLUSION: In the present study, the most commonly cultured organism was S
      aureus (53%), a finding consistent with current literature. The prevalence of P
      acnes colonization was noted in 33% of cases. Although the relevance of P acnes
      and its contribution to PJI requires further investigation, it is associated with
      PJI and biofilm formation. Based on this study, consideration could be given to
      the use of vancomycin and first-generation cephalosporins as perioperative
      antibiotic coverage.

PMID- 29178983
TI  - Hypofractionated radiotherapy for prostate cancer in the postoperative setting:
      What is the evidence so far?
AB  - Postoperative external beam radiation therapy (EBRT) is a validated treatment
      option in the adjuvant setting for prostate cancer patients with aggressive
      pathological features following radical prostatectomy (RP) or as salvage modality
      in patients with biochemical recurrence after RP. Contemporary randomized phase
      III trials have provided evidence for using hypofractionation in the definitive
      treatment setting as an alternative to standard fractionated regimens.
      Biomathematical modeling for prostate cancer fractionated EBRT associated with
      widely available refined treatment delivery techniques such as volumetric
      modulated-arc therapy with image-guided RT may improve the therapeutic ratio.
      Nevertheless, the role of hypofractionation in the postoperative setting still
      remains investigational. In this systematic review of the literature we reviewed
      the role of hypofractionation for postoperative EBRT in the adjuvant or salvage
      setting in prostate cancer patients previously treated by RP. A favorable acute
      toxicity profile with, at least, as good biochemical control rates with
      hypofractionation has been suggested. And yet conflicting results have been
      reported concerning long-term genitourinary late toxicity. Prospective studies
      are eagerly awaited to assess the role of hypofractionation in the postoperative
      setting.

PMID- 29178984
TI  - Moral imagination: Facilitating prosocial decision-making through scene imagery
      and theory of mind.
AB  - How we imagine and subjectively experience the future can inform how we make
      decisions in the present. Here, we examined a prosocial effect of imagining
      future episodes in motivating moral decisions about helping others in need, as
      well as the underlying cognitive mechanisms. Across three experiments we found
      that people are more willing to help others in specific situations after
      imagining helping them in those situations. Manipulating the spatial
      representation of imagined future episodes in particular was effective at
      increasing intentions to help others, suggesting that scene imagery plays an
      important role in the prosocial effect of episodic simulation. Path modeling
      analyses revealed that episodic simulation interacts with theory of mind in
      facilitating prosocial responses but can also operate independently. Moreover, we
      found that our manipulations of the imagined helping episode increased actual
      prosocial behavior, which also correlated with changes in reported willingness to
      help. Based on these findings, we propose a new model that begins to capture the
      multifaceted mechanisms by which episodic simulation contributes to prosocial
      decision-making, highlighting boundaries and promising future directions to
      explore. Implications for research in moral cognition, imagination, and patients
      with impairments in episodic simulation are discussed.

PMID- 29178985
TI  - A complementary role for tetraspanin superfamily member TSSC6 and ADP purinergic
      P2Y12 receptor in platelets.
AB  - Tumor-suppressing subchromosomal transferable fragment cDNA 6 (TSSC6) expression
      is restricted to hematopoietic organs and tissues where it plays a role in
      hematopoietic-cell function. The ADP purinergic receptor P2Y12 is mainly
      expressed by platelets with important clinical significance as a target for
      several clinically approved antithrombotic agents. We have previously shown a
      physical association between P2Y12 and TSSC6 in platelets. Hence our aim was to
      investigate whether this physical association is translated to functional
      effects. To investigate this possibility, we used wild-type or TSSC6 knockout
      (KO) mice treated with either PBS or 50mg/kg clopidogrel. TSSC6 KO mice treated
      with clopidogrel exhibited synergy in delayed kinetics of clot retraction,
      reduced collagen-mediated platelet aggregation, and platelet spreading on
      fibrinogen. Platelets derived from TSSC6 mice with P2Y12 blockade form smaller
      thrombi when perfused over a collagen matrix under arterial flow. Clopidogrel
      treated TSSC6 KO arterioles showed smaller and less stable thrombi with increased
      tendency to embolise in vivo. These studies demonstrate a complementary role
      between TSSC6 and P2Y12 receptor in platelets in regulating 'outside in' integrin
      alphaIIbbeta3 signalling thrombus growth and stability.

PMID- 29178986
TI  - Thrombolytic fucoidans inhibit the tPA-PAI1 complex, indicating activation of
      plasma tissue-type plasminogen activator is a mechanism of fucoidan-mediated
      thrombolysis in a mouse thrombosis model.

PMID- 29178987
TI  - Time to threshold as a new indicator of circulatory state and prognosis in
      patients with pulmonary embolism.
AB  - BACKGROUND: Bolus tracking is commonly applied in computed tomography pulmonary
      angiography. The time that it takes for contrast to reach a predefined threshold
      in the pulmonary artery is called time to threshold (TTT). TTT could be
      associated with the circulatory state, and ultimately with prognosis in patients
      with PE. AIM: The purpose of the present study was to examine the correlation of
      TTT with embolus burden, radiological and clinical parameters of circulatory
      state, and ultimately with 30-day mortality. METHODS: In a single-center,
      retrospective study 50 patients with pulmonary embolism and contrast
      administration via central venous line were included. The Mastora score was used
      to quantify embolus burden. Radiological parameters of circulatory state were the
      ratio of the short axes of the right and left ventricle diameter and the reflux
      of contrast medium into the inferior vena cava. Clinical parameters of
      circulatory state were arterial pH, systolic blood pressure, heart rate, and the
      Acute Physiology and Chronic Health Evaluation II: APACHE II. Survival was
      defined as surviving the following 30days after the PE diagnosis. RESULTS: TTT
      was significantly correlated with all radiological and clinical parameters of
      circulatory state and with 30-day mortality. However, TTT is dependent on device
      specific and protocol specific factors. CONCLUSIONS: Higher TTT is associated
      with worse prognosis in patients with pulmonary embolism.

PMID- 29178988
TI  - Adoption of Bio/Data Collagen for the assessment of platelet function with the
      Multiplate(r) Analyzer.

PMID- 29178989
TI  - Interaction of factor VII activating protease (FSAP) with neutrophil
      extracellular traps (NETs).
AB  - The circulating zymogen form of Factor VII activating protease (FSAP) can be
      activated by histones and nucleosomes in vivo. These cell-death-associated
      nuclear factors are also actively extruded into the extracellular space by
      neutrophils through a process called neutrophil extracellular trap (NET)
      formation (NETosis). NETs are thought to be involved in host defense,
      inflammation as well as thrombosis. We have investigated the bidirectional
      interactions of FSAP and NETs. Phorbol ester-mediated NET formation was
      marginally stimulated by FSAP. Plasma-derived FSAP as well as exogenous FSAP
      bound to NETs. There was co-localization of FSAP and NETs in coronary thrombi
      from patients with acute myocardial infarction. Contrary to our expectations no
      activation of pro-FSAP by NETs was evident. However, after disintegration of NETs
      with DNase, a robust activation of pro-FSAP, due to release of histones from
      nucleosomes, was detected. The released histones were in turn degraded by FSAP.
      Histone cytotoxicity towards endothelial cells was neutralized by FSAP more
      potently than by activated protein C (APC). One more consequence of histone
      degradation was a decrease in nucleosome release from apoptotic neutrophils.
      Taken together, NETs bind to FSAP, but do not activate pro-FSAP unless histones
      are released from NETs by DNAse. This activation of FSAP is likely to be
      important in diminishing the cytotoxic effect of histones, thus limiting the
      damaging effect of NETosis.

PMID- 29178990
TI  - Variants in chondroitin sulfate metabolism genes in thrombotic storm.
AB  - INTRODUCTION: Thrombotic storm (TS) presents as a severe, acute thrombotic
      phenotype, characterized by multiple clotting events and frequently affecting
      younger adults. Understanding the extensive hypercoagulation of an extreme
      phenotype as TS will also provide insight into the pathogenesis of a wider
      spectrum of thrombotic disorders. MATERIAL AND METHODS: We completed whole exome
      sequencing on 26 TS patients, including 1 multiplex family, 13 trios and 12
      isolated TS patients. We examined both dominant and recessive inheritance models
      for known thrombotic factors as well as performed a genome-wide screen.
      Identified genes of interest in the family and trios were screened in the
      remaining TS patients. Variants were filtered on frequency (<5% in 1000 genomes),
      conservation and function in gene and were annotated for effect on protein and
      overall functionality. RESULTS: We observed an accumulation of variants in genes
      linked to chondroitin sulfate (CS), but not heparan sulfate metabolism. Sixteen
      conserved, rare missense and nonsense variants in genes involved in CS metabolism
      (CHPF, CHPF2, CHST3, CHST12, CHST15, SLC26A2, PAPSS2, STAB2) were identified in
      over one-third of the TS patients. In contrast, we identified only seven variants
      in known thrombosis genes (including FV Leiden). CONCLUSIONS: As CS has multiple
      functions in the glycocalyx protecting the endothelial cells, reduced
      availability of CS could diminish the normal control mechanisms for blood
      coagulation, making these CS metabolism genes strong potential risk factors for
      TS. Overall, no single gene was identified with strong evidence for TS causality;
      however, our data suggest TS is mediated by an accumulation of rare pro
      thrombotic risk factors.

PMID- 29178991
TI  - The disseminated intravascular coagulation score is a novel predictor for portal
      vein thrombosis in cirrhotic patients with hepatitis B.
AB  - BACKGROUND: The development of portal vein thrombosis (PVT) in cirrhotic patients
      has not been fully elucidated. The disseminated intravascular coagulation (DIC)
      score, which is based on readily available and relatively inexpensive coagulation
      parameters, including platelet count, fibrin-related markers, prothrombin time
      and fibrinogen, has not been reported regarding PVT development in cirrhotic
      patients to date. We aimed to evaluate the prognostic value of the DIC score in
      predicting PVT development in cirrhotic patients with hepatitis B. MATERIAL AND
      METHODS: A total of 109 cirrhotic patients with hepatitis B were included.
      Clinical data, laboratory tests and imaging were collected from the patients at
      baseline and every three months after enrollment. All patients were followed
      until the study endpoint (either occurrence of PVT or 12months after baseline).
      We measured routine laboratory parameters and conducted imaging examinations in
      cirrhotic patients and evaluated the prognostic value of the DIC score as a novel
      predictor for PVT in patients with cirrhosis. We also compared the effectiveness
      of the DIC score with other common coagulation and hemodynamic parameters.
      RESULTS: Among the 109 patients, 14 (12.8%) developed PVT. At the study endpoint,
      significant increases in D-dimer, Child-Pugh score and DIC score (all P<0.001)
      and significantly reduced portal flow velocity (P<0.001) were noted in the PVT
      group. Among the selected factors, the DIC score had the largest area under the
      curve (AUC) (0.845), followed by the Child-Pugh score (0.778), D-dimer (0.732),
      and portal vein velocity (0.709). CONCLUSION: Among the selected factors, the DIC
      score showed non-significantly higher diagnostic performance in predicting the
      PVT development in cirrhotic patients compared with other factors. A validation
      cohort of the study is needed in the near future.

PMID- 29178992
TI  - Toxicological responses of Laeonereis acuta (Polychaeta, Nereididae) after acute,
      subchronic and chronic exposure to cadmium.
AB  - The objective of this study was to analyze the toxicological responses of the
      estuarine polychaete Laeonereis acuta after acute (96h), subchronic (7 days) and
      chronic (14 days) exposure to cadmium (Cd). Concentrations of metallothioneins
      (MT), lipid peroxidation (LPO), total Cd and metal-rich granules (MRG) were
      evaluated. Seasonal variations of MT and LPO levels in the wild were also
      measured. Polychaetes were obtained in the Quequen estuary located southeast of
      Buenos Aires Province, Argentina. For the acute toxicity assay, individuals were
      exposed to 10; 30, 65; 310; 600; 1300; 2000; 4300; 8100; 16300ugCdL-1, which
      included levels of environmental relevance and median lethal concentrations
      (LC50) for related species of polychaete. Based on 96h LC50 values, polychaetes
      were exposed to sublethal doses of Cd. The concentrations for both subchronic and
      chronic assays were: 10; 30; 65; 310; 600; 1300; 2000; 4300ugCdL-1. The 96h LC50
      value was 8234.9ugL-1, which was within the values reported for other species of
      polychaete, indicating a high tolerance to Cd. MT induction was not observed for
      any time exposure. In additoin, LPO levels showed no differences with respect to
      control levels, which indicated an absence of oxidative damage caused by Cd.
      However, the total Cd and MRG-Cd concentrations in L. acuta in all tested
      treatments showed significant differences with respect to control levels. L.
      acuta were able to accumulate Cd in their tissues in the form of granules which
      are the main mechanism of Cd detoxification.

PMID- 29178993
TI  - Improved conductivity and antibacterial activity of poly(2-aminothiophenol)
      silver nanocomposite against human pathogens.
AB  - A rapid and simple chemical synthesis of poly(2-aminothiophenol)-silver (P2ATP
      Ag) nanocomposite using conductive and electroactive silver nanoparticles (AgNPs)
      is reported. The AgNPs was synthesized by chemical reduction method using tri
      sodium citrate as reducing agent and poly(N-vinyl-2-pyrrolidone) (PVP) as
      stabilizing agent. P2ATP-Ag nanocomposite was synthesized by using potassium
      peroxodisulphate as oxidant and the samples were characterized. The presence of
      AgNPs in the composite was confirmed from UV-Vis, FTIR and X-ray diffraction
      studies. Morphology of the P2ATP and its composite were investigated by SEM. HR
      TEM images show spherical, trigonal and rod like morphologies with sizes of Ag
      nanoparticles and its composite. Thermal analysis revealed that the thermal
      stability of the P2ATP-Ag nanocomposite is improved when compared with pure
      P2ATP. The synthesized AgNPs, pure P2ATP and P2ATP-Ag nanocomposite were screened
      for antibacterial activity test against human pathogen such as Gram positive
      (Bacillus subtilis, ATCC-6051) and Gram negative (Vibrio cholerae, ATCC-14035),
      carried out by agar-well diffusion method at micro molar concentration. The
      result shows that P2ATP-Ag nanocomposite has excellent antibacterial activity due
      to the presence of Ag nanoparticles. The electrical conductivity of the P2ATP-Ag
      nanocomposite is better than that of pure P2ATP. The reported nanocomposite will
      be a potential material for electrocatalysis, sensors and biomedical
      applications.

PMID- 29178994
TI  - Green synthesis of highly fluorescent nitrogen - Doped carbon dots from Lantana
      camara berries for effective detection of lead(II) and bioimaging.
AB  - Here, we developed a simple green approach for the synthesis of highly
      fluorescent nitrogen doped carbon dots (NCDs) using Lantana camara berries.
      Optical and physicochemical properties of as synthesized NCDs were extensively
      studied by using various analytical techniques. NCDs exhibited bright
      fluorescence with Quantum yield as high as 33.15%, which is stable to various
      effects like heat, pH, ionic strength and continuous irradiation. Furthermore,
      the NCDs presented highly selective and sensitive fluorescence response towards
      Pb2+ which explored their potential to serve as a label-free fluorescent probe
      for the effective detection of Pb2+. As developed NCDs based probe exhibited a
      great linear response (R2=0.998) towards Pb2+ in the concentration range of 0
      200nM with a detection limit of 9.64nM. The probe further presented high
      precision without any interference and was successfully applied for the detection
      of Pb2+ in the real water and human sera (serum and urine) samples. Cytotoxicity
      studies on both cancerous (human breast adenocarcinoma MCF-7) and normal (Human
      embryonic kidney HEK-293) cell lines revealed their excellent biocompatibility.
      With their low cytotoxicity, strong fluorescence and excitation-dependent
      emission, NCDs were successfully applied as multi-colour bioimaging agents and
      Pb2+ detection capabilities were further evaluated in live cells.

PMID- 29178995
TI  - A new insight into the interaction of ZnO with calf thymus DNA through surface
      defects.
AB  - Experimental evidences on the binding interaction of ZnO and Calf Thymus (CT) DNA
      using several biophysical techniques are the centre of interest of the present
      study. The interaction of ZnO with CT DNA has been investigated in detail by
      absorption spectral study, fluorescence titration, Raman analysis, zeta potential
      measurement, viscometric experiment along with thermal melting study and
      microscopic analysis. Steady-state fluorescence study revealed the quenching
      (48%) of the surface defect related peak intensity of ZnO on interaction with
      DNA. The optimized concentration of ZnO and DNA to obtain this level of quenching
      has been found to be 0.049mM and 1.027MUM, respectively. Additional fluorescence
      study with 8-hydroxy-5-quinoline (HQ) as a fluorescence probe for Zn2+ ruled out
      the dissolution effect of ZnO under the experimental conditions. DNA conjugation
      on the surface of ZnO was also supported by Raman study. The quantitative
      variation in conductivity as well as electrophoretic mobility indicated
      significant interaction of ZnO with the DNA molecule. Circular dichroism (CD) and
      viscometry titrations provided clear evidence in support of the conformational
      retention of the DNA on interaction with ZnO. The binding interaction was found
      to be predominantly entropy driven in nature. The bio-physical studies presented
      in this paper exploring ZnO-CT DNA interaction could add a new horizon to
      understand the interaction between metal oxide and DNA.

PMID- 29178997
TI  - Reply by Authors.

PMID- 29178996
TI  - Analysis of Aloe vera cytotoxicity and genotoxicity associated with endodontic
      medication and laser photobiomodulation.
AB  - This study aims to evaluate, in vitro, the effect of Aloe vera associated with
      endodontic medication, with or without laser photobiomodulation (FTL) irradiation
      in FP6 human pulp fibroblasts. The materials were divided into eight groups: CTR 
      control; CL - FTL alone; AA - Aloe vera with distilled water; AL - Aloe vera
      with distilled water and FTL; HA - calcium hydroxide P.A. with distilled water;
      HL - calcium hydroxide P.A. with distilled water and FTL; HAA - calcium hydroxide
      P.A. with Aloe vera and distilled water; HAL - calcium hydroxide P.A. with Aloe
      vera, distilled water, and FTL. The cytotoxicity was evaluated by MTT assay at
      24, 48, and 72h and the genotoxicity by micronucleus test assay. This study was
      performed in triplicate. Data obtained in both tests were statistically analyzed
      by ANOVA and Tukey's tests (p<=0.05). Group AA presented high genotoxicity and
      low cytotoxicity. After 24, 48, and 72h, the group HAA significantly reduced the
      cell viability. Interaction with FTL showed slightly increase cell viability
      after 24 and 48h in groups CL and HL (p<0.001), despite the high genotoxicity in
      group CL and low genotoxicity in group HL. Group AL showed higher cell survival
      rate at 72h (p<0.05) and high genotoxicity (p<0.001). It was concluded that Aloe
      vera allowed higher cell viability in human pulp fibroblasts in the presence of
      calcium hydroxide or with FTL separately, but genotoxicity increased in these
      associations.

PMID- 29178998
TI  - Re: Predictive Nomogram for Recurrence following Surgery for Nonmetastatic Renal
      Cell Cancer with Tumor Thrombus: E. J. Abel, T. A. Masterson, J. A. Karam, V. A.
      Master, V. Margulis, R. Hutchinson, C. A. Lorentz, E. Bloom, T. M. Bauman, C. G.
      Wood and M. L. Blute, Jr. J Urol 2017;198:810-816.

PMID- 29178999
TI  - Re: Long-Term Treatment with OnabotulinumtoxinA Results in Consistent, Durable
      Improvements in Health Related Quality of Life in Patients with Overactive
      Bladder: D. A. Ginsberg, M. J. Drake, A. Kaufmann, S. Radomski, A. E. Gousse, C.
      J. Chermansky, A. Magyar, J. P. Nicandro and V. W. Nitti; 191622-096
      Investigators J Urol 2017;198:897-904.

PMID- 29179000
TI  - Reply by Authors.

PMID- 29179001
TI  - Re: Differential Expression of PD-L1 in High Grade T1 vs Muscle Invasive Bladder
      Carcinoma and its Prognostic Implications: S. A. M. Wankowicz, L. Werner, A.
      Orsola, J. Novak, M. Bowden, T. K. Choueiri, I. de Torres, J. Morote, G. J.
      Freeman, S. Signoretti and J. Bellmunt J Urol 2017;198:817-823.

PMID- 29179002
TI  - Reply by Authors.

PMID- 29179004
TI  - Words Matter.

PMID- 29179003
TI  - Facilitating Milk Donation in the Context of Perinatal Palliative Care.
AB  - The option to donate milk within the context of perinatal palliative care allows
      pregnant women to be involved in medical decision making before birth. In this
      article we examine how a perinatal bereavement program engages women and families
      in the process of milk donation when the deaths of their newborns are
      anticipated. We include two case examples to offer insight into the complexities
      within the patient experience of milk donation after perinatal loss.

PMID- 29179006
TI  - Exploring the relations among physical fitness, executive functioning, and low
      academic achievement.
AB  - Physical fitness seems to be related to academic performance, at least when
      taking the role of executive functioning into account. This assumption is highly
      relevant for the vulnerable population of low academic achievers because their
      academic performance might benefit from enhanced physical fitness. The current
      study examined whether physical fitness and executive functioning are independent
      predictors of low mathematics and spelling achievement or whether the relation
      between physical fitness and low achievement is mediated by specific executive
      functions. In total, 477 students from second- and third-grade classes of 12
      primary schools were classified as either low or average-to-high achievers in
      mathematics and spelling based on their scores on standardized achievement tests.
      Multilevel structural equation models were built with direct paths between
      physical fitness and academic achievement and added indirect paths via components
      of executive functioning: inhibition, verbal working memory, visuospatial working
      memory, and shifting. Physical fitness was only indirectly related to low
      achievement via specific executive functions, depending on the academic domain
      involved. Verbal working memory was a mediator between physical fitness and low
      achievement in both domains, whereas visuospatial working memory had a mediating
      role only in mathematics. Physical fitness interventions aiming to improve low
      academic achievement, thus, could potentially be successful. The mediating effect
      of executive functioning suggests that these improvements in academic achievement
      will be preceded by enhanced executive functions, either verbal working memory
      (in spelling) or both verbal and visuospatial working memory (in mathematics).

PMID- 29179005
TI  - Decision-making behaviors: weighing ethology, complexity, and sensorimotor
      compatibility.
AB  - Rodent decision-making research aims to uncover the neural circuitry underlying
      the ability to evaluate alternatives and select appropriate actions. Designing
      behavioral paradigms that provide a solid foundation to ask questions about
      decision-making computations and mechanisms is a difficult and often
      underestimated challenge. Here, we propose three dimensions on which we can
      consider rodent decision-making tasks: ethological validity, task complexity, and
      stimulus-response compatibility. We review recent research through this lens, and
      provide practical guidance for researchers in the decision-making field.

PMID- 29179007
TI  - Electron microscopy observations on testis and spermatozoa of Leptodactylus
      chaquensis (Anura, Leptodactylidae).
AB  - Scanning and transmission electron microscopy were used to investigate the fine
      structure of the testis and spermatozoa of toad Leptodactylus chaquensis. Our
      observations indicate that germinal compartment contains Sertoli (SC) and germ
      cells. The tight junctions and desmosomes among SC indicate the existence of an
      hematotesticular barrier in charge of maintaining the differences in the
      composition of the germinal and interstitial compartments. During
      spermatogenesis, SC acts as a structural support for germ cells. Secondary
      spermatogonias, spermatocytes and spermatids are joined by cytoplasmic bridges
      that allow communication between cells in the same cyst. Spermatids at the
      subcellular level two well-defined morphological stages can be observed: primary
      spermatids are rounded cells with an acrosomal vesicle attached to the nucleus
      which has a diameter of about 4.39+/-0.36MUm. Secondary spermatids are elongated
      with a nucleus of about 19.50+/-0.92MUm in diameter and the acrosome and the
      axoneme are located in opposite poles of the cells. At the apical end of the
      spermatozoon we can observe a large arrowhead-shaped acrosome (6.26+/-0.28MUm in
      length) that takes up about one third of the gamete head with 17.33+/-0.29MUm in
      length. The proximal centriole is located in the nuclear fossa while the distal
      centriole gives rise to the flagellar axoneme. The flagellum exhibits a typical
      pattern of "9+2" and adjacent to it is the axial fiber, and an undulating
      membrane stretches between both structures. Transmission electron microscopy
      observations allowed us to produce a diagram of the structure of the spermatozoon
      of L. chaquensis. Leydig cells, located in the interstitial compartment, show
      scarce cytoplasm, mitochondria and large-sized lipid droplets which would provide
      the raw matter for the synthesis of steroid hormones.

PMID- 29179008
TI  - Oblique illumination in microscopy: A quantitative evaluation.
AB  - Many biological objects are barely distinguished with the brightfield microscope
      because they appear transparent, translucent and colourless. One simple way to
      make such specimens visible without compromising contrast and resolution is by
      controlling the amount and the directionality of the illumination light. Oblique
      illumination is an old technique described by many scientists and microscopists
      that however has been largely neglected in favour of other alternative methods.
      Oblique lighting (OL) is created by illuminating the sample by only a portion of
      the light coming from the condenser. If properly used it can improve the
      resolution and contrast of transparent specimens such as diatoms. In this paper a
      quantitative evaluation of OL in brigthfield microscopy is presented. Several
      feature descriptors were selected for characterising contrast and sharpness
      showing that in general OL provides better performance for distinguishing minute
      details compared to other lighting modalities. Oblique lighting is capable to
      produce directionally shadowed differential contrast images allowing to observe
      phase details in a similar way to differential contrast images (DIC) but at lower
      cost. The main advantage of OL is that the resolution of the light microscope can
      be increased by effectively doubling the angular aperture. OL appears as a cost
      effective technique both for the amateur and professional scientist that can be
      used as a replacement of DIC or phase contrast when resources are scarce.

PMID- 29179009
TI  - Osteoblastic cell behaviour on modified titanium surfaces.
AB  - INTRODUCTION: The surfaces of endoosseous dental implants have been subjected to
      numerous modifications in order to create a surface which can provide rapid bone
      healing and fast implant loading. Each modification has involved changes to the
      chemical composition and topography of the surfaces which have resulted in
      various biological reactions to the implanted material. AIM: The aim of this
      study was to evaluate the surface topography and chemistry of various modified
      titanium surfaces: (1) machined surface (MA), (2) alumina-blasted (Al2O3), (3)
      alumina-blasted and acid-etched (Al2O3 DE), (4) hydroxyapatite/tricalcium
      phosphate grit-blasted (HA/TCP) and (5) hydroxyapatite/tricalcium phosphate grit
      blasted and acid-etched (HA/TCP DE) and to analyse the effects of surface
      roughness, and chemical composition on human osteoblast vitality,
      differentiation, morphology and orientation. MATERIALS AND METHODS: The modified
      surfaces were subjected to topographic analysis using Scanning Electron
      Microscopy (SEM), optical profilometry, roughness analysis and chemical
      composition evaluation using Energy Dispersion Spectroscopy (EDS) analysis. The
      biological effects of the titanium modifications was analysed using human
      osteoblasts cell culture where the cell morphology, vitality (MTS assay) and
      differentiation (ALP activity) was analysed. RESULTS: The machined surfaces were
      classified as anisotropic, smooth and composed of titanium and oxygen. The
      blasted surface samples along with the blasted and etched samples were found to
      be isotropic and rough. The grit-blasting procedure resulted in the incorporation
      of components from the blasting material. In the case of the blasted and etched
      samples, etching decreased the surface development as indicated by the Sdr and
      also reduced the amount of chemical compounds incorporated into the surfaces
      during the blasting procedure. The attached NHOst cells, proliferated the
      surfaces. With regard to the MA samples, the cells spread close to the titanium
      surface, with expanded cytoplasmic extensions and lamelipodia and were oriented
      in line with the groves left after machining. On the rough substrates, cells were
      less dispersed and exhibited numerous cytoplasmic extensions, filopodia and
      interconnections, they were not oriented with respect to the surfaces features.
      The cell viability of all samples except for Al2O3 decreased after the first day
      of culture. For all Al2O3, Al2O3 DE and HA samples the viability increased with
      culture time after an initial reduction. At the end of the culture period the ALP
      activity was slightly greater on Al2O3 and HA samples compared to the control
      with the HA DE sample having the same activity as the control. The Al2O3, HA and
      HA DE ALP samples showed comparable activity and were statistically different
      from MA and Al2O3 DE samples. CONCLUSIONS: In this study, variously treated
      titanium surfaces were correlated with osteoblastic cell viability, morphology
      and differentiation in comparison with the plastic and smooth titanium. All
      examined surfaces were found to be biocompatible. Favourable cell reactions were
      observed for Al2O3 and HA blasted surfaces. The surface roughness patterns
      influenced the growth orientation while the surface topography influenced
      osteoblast morphology. Further animal studies are necessary to compare the in
      vivo effect on osseointegration of these modified titanium surfaces.

PMID- 29179010
TI  - Method for estimating modulation transfer function from sample images.
AB  - The modulation transfer function (MTF) represents the frequency domain response
      of imaging modalities. Here, we report a method for estimating the MTF from
      sample images. Test images were generated from a number of images, including
      those taken with an electron microscope and with an observation satellite. These
      original images were convolved with point spread functions (PSFs) including those
      of circular apertures. The resultant test images were subjected to a Fourier
      transformation. The logarithm of the squared norm of the Fourier transform was
      plotted against the squared distance from the origin. Linear correlations were
      observed in the logarithmic plots, indicating that the PSF of the test images can
      be approximated with a Gaussian. The MTF was then calculated from the Gaussian
      approximated PSF. The obtained MTF closely coincided with the MTF predicted from
      the original PSF. The MTF of an x-ray microtomographic section of a fly brain was
      also estimated with this method. The obtained MTF showed good agreement with the
      MTF determined from an edge profile of an aluminum test object. We suggest that
      this approach is an alternative way of estimating the MTF, independently of the
      image type.

PMID- 29179011
TI  - IVF outcome in azoospermic cancer survivors.
AB  - OBJECTIVE: To assess clinical outcome among infertile couples treated by in vitro
      fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) using testicular
      sperm from azoospermic cancer survivors. STUDY DESIGN: This clinical
      retrospective study included infertile couples treated in a single tertiary
      referral center between 1996 and 2013. All male partners were cancer survivors
      who were diagnosed with azoospermia due to previous gonadotoxic treatments and
      referred to testicular sperm extraction (TESE). Retrieved sperm was used for IVF
      ICSI among patients' spouses. Sperm retrieval rate and IVF-ICSI outcome were
      evaluated. RESULTS: Sperm was successfully retrieved in 12 out of 36 patients
      (33.3%) on initial TESE, with an overall sperm retrieval rate of 38.6% (17 of
      44). Female patients were 29.8+/-5.1 years old. The average number of retrieved
      oocytes was 14.0+/-4.0 per cycle, with clinical pregnancy and live birth rates
      per successful TESE of 64% (11 of 17) and 58.8% (10 of 17), respectively. Age,
      serum FSH, testicular volume and time from chemotherapy to TESE were not
      significantly different between patients with successful TESE to those without.
      Patients suffering from seminomas had significantly higher sperm retrieval rate,
      as compared to patients who had Hodgkin's lymphoma (P=0.024). CONCLUSIONS: Post
      chemotherapy azoospermia can be successfully treated with TESE and ICSI, and
      should be offered to azoospermic cancer survivors who did not cryopreserve sperm
      prior to their gonadotoxic treatments.

PMID- 29179012
TI  - Reproducibility of the transvaginal sonographic assessment of bladder wall
      thickness.
AB  - OBJECTIVE: To assess whether transvaginal sonographic measurements of bladder
      wall thickness (BWT) have adequate reproducibility to detect differences in BWT
      potentially indicative of detrusor overactivity in women with overactive bladder.
      STUDY DESIGN: Three reproducibility studies were undertaken to assess (A) total
      measurement error, (B) intra-observer variability and (C) inter-observer
      measurement in the interpretation of scans. Women recruited to the Bladder
      Ultrasound Study underwent a transvaginal ultrasound scan to obtain a measurement
      of BWT. When a second observer was available, women who agreed to have two
      transvaginal scans by different operators were recruited into study A. For study
      B the first observer reassessed a sample of the recorded images at a later date
      whilst for study C, a random selection of BWT images were read by a second
      assessor. Analytical variability, percentage of variability attributable to
      measurement error, within-person variation and the smallest real difference
      detectable were estimated. RESULTS: One hundred and twenty-one women took part:
      27 had repeat scans, 37 had scans re-read by the same observer, and 57 had scans
      read by two observers. In study A, 39% of the total variability in measurements
      was explained by measurement error (the remainder to within person change); the
      standard deviation (SD) of measurement error was 0.76mm and the smallest
      detectable clinical difference was 2.1mm. The SD of measurement error from scan
      interpretation was 0.42mm within observers (study B) and 0.35mm between observers
      (studyC). CONCLUSION: The high levels of measurement error for a small
      measurement of BWT means it is unlikely Transvaginal ultrasound measurements have
      insufficient reliability and reproducibility to be an accurate diagnostic test.

PMID- 29179013
TI  - Increased systemic microbial translocation is associated with depression during
      early pregnancy.
AB  - Plasma level of microbial translocation is a marker of mucosal permeability.
      Increased mucosal permeability ignites elevated microbial translocation and as a
      consequence of systemic inflammation. Pregnant women with depression have higher
      levels of inflammatory markers relative to pregnant women without depression,
      however, no studies have reported whether systemic microbial translocation will
      change in depressed women during pregnancy. In this study, we examined the plasma
      LPS level of depressed women during pregnancy. The results showed that the plasma
      LPS level was significantly increased in depressed mothers during their 8-12
      weeks gestation compared to healthy controls. Compared to 8-12 weeks gestation,
      the plasma LPS levels were significantly decreased at 24-28 weeks gestation and 6
      8 weeks postpartum in both depressed subjects and healthy controls. Furthermore,
      the plasma levels of pro-inflammatory cytokines (TNF-alpha and MCP/CCL2)
      associated with microbial translocation were significantly increased in depressed
      subjects during 8-12 weeks gestation compared to healthy controls. These results
      indicate that the level of microbial translocation is increased in depressed
      women during early pregnancy.

PMID- 29179014
TI  - Clinical utility of biomarkers of the hand in the diagnosis of schizophrenia.
AB  - A number of biomarkers were assessed in photos and prints of the hands of 95
      patients with a variety of mental disorders to determine whether patients with
      schizophrenia could be distinguished from the others. Patients were recruited as
      consecutive admissions from an outpatient psychiatric day hospital population.
      Fourteen patients were diagnosed with schizophrenia/schizoaffective disorder and
      81 were diagnosed with other mental disorders. A discriminant analysis yielded an
      overall 80% correct classification, with a sensitivity (schizophrenia patients
      identified correctly) of 78.6% and a specificity (non-schizophrenia patients
      identified correctly) of 80.2%. Significant differences were noted in the
      proximal interphalangeal joint, eponychium of the middle digit and fingernails.
      To determine biomarker frequency distribution patients with bipolar disorder were
      then compared to those with schizophrenia/schizoaffective disorder and then to
      patients with PTSD. The former yielded an overall 78.6% correct classification,
      with a sensitivity of 71.4% and a specificity of 85.7% and with similar biomarker
      frequency distribution for bipolar disorder as for the entire non schizophrenia
      group. The latter comparison yielded an overall 58.6% correct classification,
      with no significant differences between the features. The application of these
      biomarkers in clinical practice could constitute an additional tool for the
      psychiatrist in cases lacking diagnostic clarity.

PMID- 29179015
TI  - Serum levels of interleukins IL-6 and IL-10 in individuals with posttraumatic
      stress disorder in a population-based sample.
AB  - To evaluate the serum levels of IL-6 and IL-10 anti-inflammatory interleukins in
      individuals with post-traumatic stress disorder (PTSD) in a population-based
      study. This is a paired study nested in a cross-sectional population-based study.
      All individuals who presented PTSD and did not present major depressive disorder,
      diagnostic by interview--Mini International Neuropsychiatric Interview were
      selected. From these, 41 healthy controls were matched by sex and age. Serum
      levels of IL-6 and IL-10 were measured by the ELISA, using commercial kits. The
      group of individuals with PTSD showed a significant increase in the serum levels
      of IL-6 and IL-10. Our results suggest that individuals with PTSD may present an
      activation of the immune system, which may lead to neuroinflammation.

PMID- 29179016
TI  - Group family-based cognitive behavioral therapy for pediatric obsessive
      compulsive disorder: Global outcomes and predictors of improvement.
AB  - This open, uncontrolled study examined the efficacy of a group family-based
      cognitive behavioral therapy (GF-CBT) protocol in treating pediatric obsessive
      compulsive disorder (OCD) and explored predictors of symptom improvement. Eighty
      five OCD-affected youth aged 8-18 years (M = 13.9 years, SD = 2.49; 46% male) and
      their parent(s) participated in a weekly, 12-session GF-CBT program. Data from
      multiple perspectives were gathered at the beginning and end of treatment, as
      well as at one-month follow-up. A broad range of assessment measures were
      utilized to capture clinically-relevant domains and a number of potential
      predictor variables were explored. Paired t-tests indicated that treatment was
      associated with significant reductions in clinician- and parent-rated OCD
      severity (d = 1.47, 1.32), youth and parent-rated functional impairment (d =
      0.87, 0.67), coercive/disruptive behaviors (d = 0.75), and family accommodation
      (d = 1.02), as well as improvements in youth-, mother-, and father-rated family
      functioning (d = 1.05, 0.50, 0.88). Paired t-tests also indicated that youth
      remained improved at one-month follow-up. Step-wise regression identified greater
      homework success as a significant predictor of symptom improvement. This study
      provides evidence that GF-CBT significantly improves a wide range of domains for
      youth/families that extends beyond OCD symptom severity and supports homework as
      a core treatment component.

PMID- 29179017
TI  - Intimate partner violence and disordered eating among male and female veterans.
AB  - Intimate partner violence (IPV) affects many women and men in the United States
      and has been associated with numerous mental health conditions, including
      disordered eating (DE). Veterans may be especially vulnerable to experiencing
      both of these serious problems given the unique aspects and stressors relevant to
      military culture, including high rates of trauma exposure. We aimed to estimate
      the prevalence of past-year IPV among independent samples of male (N = 642) and
      female (N = 198) veterans and to examine the association between past-year IPV
      and DE. Mplus 7.0 was used to estimate associations between multiple types of IPV
      and DE, controlling for age, body mass index, military sexual trauma, and other
      military trauma. Approximately 14.86% of male veterans and 12.79% of female
      veterans reported experiencing some form of past-year IPV. All forms of past-year
      IPV, including physical, sexual, and psychological/emotional, were significantly
      associated with DE in both samples, after adjusting for covariates. IPV was
      relatively common among male and female veterans, and those who experience IPV
      may be particularly vulnerable to DE. Findings extend the knowledge base
      regarding IPV and its health effects among an understudied population, and may be
      a catalyst for further research and clinical inquiry to target improving
      psychiatric care for male and female veterans who experience IPV.

PMID- 29179018
TI  - Analytic processing of distance.
AB  - How does a human observer extract from the distance between two frontal points
      the component corresponding to an axis of a rectangular reference frame? To find
      out we had participants classify pairs of small circles, varying on the
      horizontal and vertical axes of a computer screen, in terms of the horizontal
      distance between them. A response signal controlled response time. The error rate
      depended on the irrelevant vertical as well as the relevant horizontal distance
      between the test circles with the relevant distance effect being larger than the
      irrelevant distance effect. The results implied that the horizontal distance
      between the test circles was imperfectly extracted from the overall distance
      between them. The results supported an account, derived from the Exemplar Based
      Random Walk model (Nosofsky & Palmieri, 1997), under which distance
      classification is based on the overall distance between the test circles, with
      relevant distance being extracted from overall distance to the extent that the
      relevant and irrelevant axes are differentially weighted so as to reduce the
      contribution of irrelevant distance to overall distance. The results did not
      support an account, derived from the General Recognition Theory (Ashby & Maddox,
      1994), under which distance classification is based on the relevant distance
      between the test circles, with the irrelevant distance effect arising because a
      test circle's perceived location on the relevant axis depends on its location on
      the irrelevant axis, and with relevant distance being extracted from overall
      distance to the extent that this dependency is absent.

PMID- 29179019
TI  - Specific and non-specific match effects in negative priming.
AB  - The negative priming effect occurs when withholding a response to a stimulus
      impairs generation of subsequent responding to a same or a related stimulus. Our
      goal was to use the negative priming procedure to obtain insights about the
      memory representations generated by ignoring vs. attending/responding to a prime
      stimulus. Across three experiments we observed that ignoring a prime stimulus
      tends to generate higher identity-independent, non-specific repetition effects,
      owing to an overlap in the coarse perceptual form of a prime distractor and a
      probe target. By contrast, attended repetition effects generate predominantly
      identity-specific sources of facilitation. We use these findings to advocate for
      using laboratory phenomena to illustrate general principles that can be of
      practical use to non-specialists. In the case of the negative priming procedure,
      we propose that the procedure provides a useful means for investigating
      attention/memory interactions, even if the specific cause (or causes) of negative
      priming effects remain unresolved.

PMID- 29179020
TI  - Different patterns of modality dominance across development.
AB  - The present study sought to better understand how children, young adults, and
      older adults attend and respond to multisensory information. In Experiment 1,
      young adults were presented with two spoken words, two pictures, or two word
      picture pairings and they had to determine if the two stimuli/pairings were
      exactly the same or different. Pairing the words and pictures together slowed
      down visual but not auditory response times and delayed the latency of first
      fixations, both of which are consistent with a proposed mechanism underlying
      auditory dominance. Experiment 2 examined the development of modality dominance
      in children, young adults, and older adults. Cross-modal presentation attenuated
      visual accuracy and slowed down visual response times in children, whereas older
      adults showed the opposite pattern, with cross-modal presentation attenuating
      auditory accuracy and slowing down auditory response times. Cross-modal
      presentation also delayed first fixations in children and young adults.
      Mechanisms underlying modality dominance and multisensory processing are
      discussed.

PMID- 29179021
TI  - How social information affects information search and choice in probabilistic
      inferences.
AB  - When making decisions, people are often exposed to relevant information stemming
      from qualitatively different sources. For instance, when making a choice between
      two alternatives people can rely on the advice of other people (i.e., social
      information) or search for factual information about the alternatives (i.e., non
      social information). Prior research in categorization has shown that social
      information is given special attention when both social and non-social
      information is available, even when the social information has no additional
      informational value. The goal of the current work is to investigate whether
      framing information as social or non-social also influences information search
      and choice in probabilistic inferences. In a first study, we found that framing
      cues (i.e., the information used to make a decision) with medium validity as
      social increased the probability that they were searched for compared to a task
      where the same cues were framed as non-social information, but did not change the
      strategy people relied on. A second and a third study showed that framing a cue
      with high validity as social information facilitated learning to rely on a non
      compensatory decision strategy. Overall, the results suggest that social in
      comparison to non-social information is given more attention and is learned
      faster than non-social information.

PMID- 29179022
TI  - Re-engineering of protein motors to understand mechanisms biasing random motion
      and generating collective dynamics.
AB  - A considerable amount of insight into the mechanisms of protein-based
      biomolecular motors has been accumulated over decades of research. However, our
      knowledge about the design principles of these motors is still limited. Even less
      is known about the design of multi-motor systems that perform various functions
      within the cell. Here we focus on constructive (or synthetic) approaches to
      biomolecular motors that could make a breakthrough in our understanding. Recent
      achievements include studies at different hierarchical levels of complexity: re
      engineering of individual motors, construction of multi-motor systems, and
      generation of large-scale complex behaviour. We then propose a strategy where the
      collective behaviour can be repeatedly tested upon modifying individual motors,
      which may provide important clues about how biomolecular motors and their systems
      are designed.

PMID- 29179023
TI  - Validation of a low field Rheo-NMR instrument and application to shear-induced
      migration of suspended non-colloidal particles in Couette flow.
AB  - Nuclear magnetic resonance rheology (Rheo-NMR) is a valuable tool for studying
      the transport of suspended non-colloidal particles, important in many commercial
      processes. The Rheo-NMR imaging technique directly and quantitatively measures
      fluid displacement as a function of radial position. However, the high field
      magnets typically used in these experiments are unsuitable for the industrial
      environment and significantly hinder the measurement of shear stress. We
      introduce a low field Rheo-NMR instrument (1H resonance frequency of 10.7MHz),
      which is portable and suitable as a process monitoring tool. This system is
      applied to the measurement of steady-state velocity profiles of a Newtonian
      carrier fluid suspending neutrally-buoyant non-colloidal particles at a range of
      concentrations. The large particle size (diameter >200MUm) in the system studied
      requires a wide-gap Couette geometry and the local rheology was expected to be
      controlled by shear-induced particle migration. The low-field results are
      validated against high field Rheo-NMR measurements of consistent samples at
      matched shear rates. Additionally, it is demonstrated that existing models for
      particle migration fail to adequately describe the solid volume fractions
      measured in these systems, highlighting the need for improvement. The low field
      implementation of Rheo-NMR is complementary to shear stress rheology, such that
      the two techniques could be combined in a single instrument.

PMID- 29179024
TI  - Effects of brief mindfulness and loving-kindness meditation inductions on
      emotional and behavioral responses to social rejection among individuals with
      high borderline personality traits.
AB  - Borderline personality disorder (BPD) is characterized by an enduring pattern of
      instability across affective, behavioral, cognitive, and interpersonal domains.
      Individuals with BPD are known to be particularly vulnerable to experiences of
      social rejection, but little work has examined strategies that may moderate their
      reactivity to social rejection. Using a laboratory experimental approach, this
      study investigated the effects of brief mindfulness and loving-kindness
      meditation (LKM) inductions on emotional and behavioral responses to social
      rejection in a sample of adults with high BPD traits. One hundred and eighteen
      participants were randomly assigned to receive 10 min of mindful breathing
      practice, LKM, or a no-instruction control condition, prior to exposure to a
      social rejection manipulation. Participants rated their emotions and completed a
      competitive reaction time task, which provided a proxy measure of aggression.
      Compared to the control condition, the mindfulness group demonstrated
      significantly quicker recovery in negative affect and feelings of rejection after
      social rejection. The mindfulness group also reported significantly quicker
      recovery in negative affect compared to the LKM group. Whereas baseline trait
      mindfulness negatively predicted aggressive behaviors across all participants,
      groups did not differ in immediate emotional reactivity or aggressive behavior
      following social rejection. The findings suggest that mindfulness training may be
      a promising strategy in alleviating negative emotional effects of social
      rejection among individuals with high borderline personality traits, and
      highlight the limited utility of brief LKM practice in buffering the effects of
      social rejection.

PMID- 29179025
TI  - Heterogeneity in the impact of type of schooling on adult health and lifestyle.
AB  - Using data from a major educational reform in England and Wales, we examine
      heterogeneity in the long-term impacts of the exposure to different secondary
      schooling systems, characterized by selective early-tracking system versus non
      selective comprehensive schooling, on health outcomes and smoking. We adopt a
      local instrumental variables approach to estimate person-centered treatment (PeT)
      effects, thereby recovering the full distribution of individual-level causal
      effects. We find that the transition from a selective early-tracking system to a
      non-selective one produced, on a fraction of individuals, significantly increased
      depression and cigarette smoking. These effects were persistent over time.
      Cognitive abilities did not moderate the effects, but students with lower non
      cognitive skills were most likely to be negatively affected by this exposure.

PMID- 29179026
TI  - Is retirement good for men's health? Evidence using a change in the retirement
      age in Israel.
AB  - This study examines the effect of employment on elderly men's health. A typical
      OLS analysis yields a positive relationship between employment and health for
      individuals in their sixties. Causality, however, is difficult to infer because
      healthier individuals are more capable of working than others. To overcome this
      endogeneity problem, this paper exploits the increase in the full retirement age
      for men in Israel from sixty-five to sixty-seven in 2004. After this change, the
      employment rate of men in this age bracket jumped significantly compared to the
      last cohort that was able to retire at sixty-five. Using the new retirement law
      as an exogenous source of variation in the employment status of elderly men, a
      significant causal relationship in the opposite direction of the correlation is
      found: employment at older ages impairs health. These findings are found across a
      broad array of datasets and health outcomes. The results are significantly
      stronger among less-educated workers, suggesting that employment in physically
      demanding occupations is more detrimental to health. Placebo analyses using the
      years preceding the new retirement regime and other health measures unrelated to
      employment (e.g., dentist visits) reinforce a causal interpretation of my main
      findings.

PMID- 29179027
TI  - The effect of smoking on obesity: Evidence from a randomized trial.
AB  - This paper aims to identify the causal effect of smoking on body mass index (BMI)
      using data from the Lung Health Study, a randomized trial of smoking cessation
      treatments. Since nicotine is a metabolic stimulant and appetite suppressant,
      quitting or reducing smoking could lead to weight gain. Using randomized
      treatment assignment to instrument for smoking, we estimate that quitting smoking
      leads to an average long-run weight gain of 1.8-1.9 BMI units, or 11-12 pounds at
      the average height. Semi-parametric models provide evidence of a diminishing
      marginal effect of smoking on BMI, while subsample regressions show that the
      impact is largest for younger individuals, those with no college degree, and
      those in the lowest quartile of baseline BMI.

PMID- 29179028
TI  - Kinematic analysis of scapular movements in patients with facioscapulohumeral
      muscular dystrophy.
AB  - The purpose of this study is to evaluate scapular movements by the three
      dimensional electromagnetic system during shoulder elevation in FSHMD patients,
      and to compare the results with healthy individuals. 10 patients with FSHMD and
      10 healthy individuals were included in the study. Scapular anterior-posterior
      tilt, upward-downward rotation and internal-external rotation at 30 degrees , 60
      degrees  and 90 degrees  were evaluated using the three-dimensional
      electromagnetic system during the elevation of the upper limbs in the scapular
      plane. Humerothoracic elevation levels on the dominant and non-dominant sides
      were found to be lower in the patients than healthy individuals (p < .001). Both
      scapula were rotated downwards at 30 degrees  (dominant/non-dominant p < .001)
      and 60 degrees  (dominant p = .009, non-dominant p = .04) of humerothoracic
      elevation, the scapula was rotated internally at 30 degrees  of humerothoracic
      elevation on the non-dominant side (p = .03), and the scapula was tilted
      posteriorly at 90 degrees  of humerothoracic elevation on the non-dominant side
      (p = .009) in patients. These existing abnormal patterns of the scapula in the
      patients increase the risk of impairment, pain, impingement and instability
      especially in the activities that require arm elevation. It is thought that
      physiotherapy approaches should first be emphasized to improve scapular
      stabilization and strengthening exercises should then be performed for the
      shoulder girdle muscles.

PMID- 29179029
TI  - 3EZ, 20Ac-ingenol induces cell-specific apoptosis in cyclin D1 over-expression
      through the activation of ATR and downregulation of p-Akt.
AB  - Acute lymphoblastic leukemia (ALL) samples exhibit an activated PI3K/Akt pathway,
      which suggests a general role of Akt in the development of leukemia. We have
      previously used western blot analysis to show that the catalytic topoisomerase
      (topo) inhibitor, 3EZ, 20Ac-ingenol, induced DNA damage response (DDR), which
      activated ATR, downregulated p-Akt through upregulation of PTEN level, and led to
      cell cycle arrest or apoptosis. In this study, we used ATR or PTEN siRNA and
      observed that the specific cell arrest and apoptosis of BALL-1 cells in DDR
      caused by 3EZ, 20Ac-ingenol was dependant on activation of ATR and downregulation
      of nuclear p-Akt through upregulation of PTEN. Moreover, some B cell lymphomas
      among ALLs overexpress cyclin D1. The DDR induced during the S-phase with 3EZ,
      20Ac-ingenol treatment was increased by the intra S-phase checkpoint response
      that was triggered by the loss of nuclear cyclin D1 regulation in BALL-1 cells
      overexpressing cyclin D1. Although topo 1 catalytic inhibitors induce a
      decatenation checkpoint and subsequent G2/M phase arrest, the decatenation
      checkpoint caused by 3EZ, 20Ac-ingenol induced apoptosis only in the BALL-1 cells
      that accumulated cyclin D1.

PMID- 29179030
TI  - Efficacy of species-specific probiotic Pediococcus acidilactici FT28 on blood
      biochemical profile, carcass traits and physicochemical properties of meat in
      fattening pigs.
AB  - The present study investigates the influence of supplementing Pediococcus
      acidilactici strain FT28 on serum biochemistry, carcass and physicochemical
      properties of meat in fattening pigs. A total of 36 piglets (28day) were randomly
      divided into three groups of four replicates of three animals in each. Each group
      was fed one of the experimental diet as basal diet alone (Control-T0); basal diet
      supplemented with Pediococcus acidilactici strain FT28 (swine origin probiotic
      T1) and basal diet supplemented with Lactobacillus acidophilus NCDC-15 (dairy
      origin probiotic-T2). Increased (P<0.05) level of serum total protein and
      albumin, and decreased (P<0.05) triglyceride were observed with probiotic
      supplementation either of swine or dairy origin, compared to control. The level
      globulin and glucose were higher (P<0.05) in T1 group among the dietary groups.
      Carcass traits remained unaltered except for the weight of ham, kidney and spleen
      which were higher (P<0.05) in the T1 group. Water holding capacity and TBARS were
      improved (P<0.05) in the T1 group than control, however comparable to the T2
      group. The ether extract, pH and sensory attributes (juiciness and appearance)
      were improved (P<0.05) in the T1 group among the dietary groups. It is evident
      from the present study that P. acidilactici FT28 could serve as probiotic for
      enhancing carcass quality and physicochemical properties of pork without
      influencing the blood metabolites.

PMID- 29179031
TI  - Innate immune responses to metabolic stress can be detected in rumen fluids.
AB  - Many production diseases of dairy cows are related to digestive troubles. The
      rumen subacute acidosis is the most relevant one, albeit not easily recognized.
      Recent studies suggest that forestomachs can perform regulatory actions at both
      regional and systemic levels, since forestomach walls express immune receptors
      and cytokines, and the rumen liquor is infiltrated by leukocytes. Therefore, the
      rumen fluid could be conveniently collected for investigating metabolic
      production diseases. Thus, we investigated the origin of the leukocytes of the
      rumen fluid and demonstrated that they partly derive from saliva. Next, we
      carried out a field survey of innate immunity in rumen fluids of 128 cows from 12
      dairy farms, along with clinical inspections, assessment of milk yield, rumen pH,
      volatile fatty acids (VFA) and major inflammo-metabolic parameters. Significant
      statistical correlations were found between immune markers in rumen fluids and
      biochemical parameters. A significant negative correlation was found in rumen
      between CD45 gene expression (leukocyte infiltration) and pH level. B cells were
      the most frequent mononuclear leukocyte population in the rumen liquor and their
      infiltration was negatively affected by low ruminal pH and high concentrations of
      VFA. Moreover, total Ig and IgM in rumen fluids were negatively correlated with
      ruminal pH and positively correlated with uremia. Our data suggest that
      forestomach immune responses could be directed to "dangers" arising within the
      forestomach environment. The immune markers could integrate consolidated
      diagnostic parameters (e.g. rumen pH) and contribute to robust, early diagnosis
      of tricky digestive troubles of cattle.

PMID- 29179032
TI  - Lower limb muscle volume estimation from maximum cross-sectional area and muscle
      length in cerebral palsy and typically developing individuals.
AB  - BACKGROUND: Deficits in muscle volume may be a significant contributor to
      physical disability in young people with cerebral palsy. However, 3D measurements
      of muscle volume using MRI or 3D ultrasound may be difficult to make routinely in
      the clinic. We wished to establish whether accurate estimates of muscle volume
      could be made from a combination of anatomical cross-sectional area and length
      measurements in samples of typically developing young people and young people
      with bilateral cerebral palsy. METHODS: Lower limb MRI scans were obtained from
      the lower limbs of 21 individuals with cerebral palsy (14.7+/-3years, 17 male)
      and 23 typically developing individuals (16.8+/-3.3years, 16 male). The volume,
      length and anatomical cross-sectional area were estimated from six muscles of the
      left lower limb. FINDINGS: Analysis of Covariance demonstrated that the
      relationship between the length*cross-sectional area and volume was not
      significantly different depending on the subject group. Linear regression
      analysis demonstrated that the product of anatomical cross-sectional area and
      length bore a strong and significant relationship to the measured muscle volume
      (R2 values between 0.955 and 0.988) with low standard error of the estimates of
      4.8 to 8.9%. INTERPRETATION: This study demonstrates that muscle volume may be
      estimated accurately in typically developing individuals and individuals with
      cerebral palsy by a combination of anatomical cross-sectional area and muscle
      length. 2D ultrasound may be a convenient method of making these measurements
      routinely in the clinic.

PMID- 29179033
TI  - Validation of the Arm Profile Score in assessing upper limb functional
      impairments in people with multiple sclerosis.
AB  - BACKGROUND: Although upper limb (UL) impairments are widespread in people with
      Multiple Sclerosis (pwMS), there is limited quantitative evidence concerning
      their specific features. The aim of this study is to validate a synthetic measure
      based on kinematic data to define the degree of deviation from a physiologic
      pattern during the "hand to mouth" (HTM) task. METHODS: Twenty pwMS (mean age
      51.2 SD 11.1) years, Expanded Disability Status Scale (EDSS) score in the range 2
      6.5, underwent a kinematic analysis of the HTM task using a motion capture
      system. Spatio-temporal parameters and synthetic indexes (Arm Variable Score, AVS
      and Arm Profile Score, APS) were calculated and compared with those of age
      matched healthy individuals. Kinematic data were correlated with the EDSS score
      and clinical tests such as the Nine Hole Peg Test (NHPT) and hand-grip strength
      (HGS). FINDINGS: PwMS exhibit reduced velocity, increased movement duration, sway
      of adjusting and frequency of direction changes as well as higher APS values
      (15.4 degrees  vs. 8.6 degrees , P<0.001) with respect to controls due to
      alterations in trunk flexion-extension, shoulder abduction-adduction, flexion
      extension and rotation and elbow flexion-extension. Moderate-to-large
      correlations were found between APS and EDSS (rho=0.609, P<0.001), NHPT
      (rho=0.468, P=0.03) and HGS (rho=-0.627 P<0.001). INTERPRETATION: The kinematic
      analysis of HTM provides useful information in quantifying UL impairments in
      pwMS. The APS index appears suitable to represent UL movement deviations from the
      physiological pattern in pwMS and to assess disease progression or effectiveness
      of pharmacologic and rehabilitative treatments effectiveness.

PMID- 29179035
TI  - Generation of a TALEN-mediated, p63 knock-in in human induced pluripotent stem
      cells.
AB  - The expression of p63 in surface ectodermal cells during development of the
      cornea, skin, oral mucosa and olfactory placodes is integral to the process of
      cellular self-renewal and the maintenance of the epithelial stem cell status.
      Here, we used TALEN technology to generate a p63 knock-in (KI) human induced
      pluripotent stem (hiPS) cell line in which p63 expression can be visualized via
      enhanced green fluorescent protein (EGFP) expression. The KI-hiPS cells
      maintained pluripotency and expressed the stem cell marker gene, DeltaNp63alpha.
      They were also able to successfully differentiate into functional corneal
      epithelial cells as assessed by p63 expression in reconstructed corneal
      epithelium. This approach enables the tracing of p63-expressing cell lineages
      throughout epithelial development, and represents a promising application in the
      field of stem cell research.

PMID- 29179036
TI  - Bilateral facial nerve palsies secondary to chronic inflammatory demyelinating
      polyneuropathy following adalimumab treatment.
AB  - PURPOSE: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) presents
      uncommonly with cranial nerve involvement with ophthalmological implications.
      METHODS: We report the case of a 37year-old man who developed CIDP which
      manifested as progressive and relapsing bilateral facial nerve palsy with
      lagophthalmos and exposure keratopathy, in the setting of treatment of Crohn's
      disease with the anti-TNF-alpha agent adalimumab. RESULTS: Symptoms gradually
      improved over the course of several months following withdrawal of adalimumab and
      treatment with intravenous immunoglobulin (IVIg) and oral prednisolone.
      CONCLUSION: Bilateral facial nerve involvement occurs uncommonly as a feature of
      CIDP in its classic form. The prognosis is good for recovery of facial nerve
      function with discontinuation of anti-TNF-alpha therapy and concurrent use of
      steroid and intravenous immunoglobulin in this case.

PMID- 29179034
TI  - Effects of exposure to water disinfection by-products in a swimming pool: A
      metabolome-wide association study.
AB  - BACKGROUND: Exposure to disinfection by-products (DBPs) in drinking water and
      chlorinated swimming pools are associated with adverse health outcomes, but
      biological mechanisms remain poorly understood. OBJECTIVES: Evaluate short-term
      changes in metabolic profiles in response to DBP exposure while swimming in a
      chlorinated pool. MATERIALS AND METHODS: The PISCINA-II study (EXPOsOMICS
      project) includes 60 volunteers swimming 40min in an indoor pool. Levels of most
      common DBPs were measured in water and in exhaled breath before and after
      swimming. Blood samples, collected before and 2h after swimming, were used for
      metabolic profiling by liquid-chromatography coupled to high-resolution mass
      spectrometry. Metabolome-wide association between DBP exposures and each
      metabolic feature was evaluated using multivariate normal (MVN) models.
      Sensitivity analyses and compound annotation were conducted. RESULTS: Exposure
      levels of all DBPs in exhaled breath were higher after the experiment. A total of
      6,471 metabolic features were detected and 293 features were associated with at
      least one DBP in exhaled breath following Bonferroni correction. A total of 333
      metabolic features were associated to at least one DBP measured in water or
      urine. Uptake of DBPs and physical activity were strongly correlated and mutual
      adjustment reduced the number of statistically significant associations. From the
      293 features, 20 could be identified corresponding to 13 metabolites including
      compounds in the tryptophan metabolism pathway. CONCLUSION: Our study identified
      numerous molecular changes following a swim in a chlorinated pool. While we could
      not explicitly evaluate which experiment-related factors induced these
      associations, molecular characterization highlighted metabolic features
      associated with exposure changes during swimming.

PMID- 29179037
TI  - Nuclear myosin 1 associates with papillomavirus E2 regulatory protein and
      influences viral replication.
AB  - Nuclear myosin 1c (NM1) associates with RNA polymerases and is a partner in the
      chromatin remodeling complex B-WICH. This complex, which also contains WSTF and
      SNF2h proteins, is involved in transcriptional regulation. We report herein that
      papillomavirus protein E2 binds to NM1 and co-precipitates with the WSTF and
      SNF2h proteins. Our data suggest that E2 associates with the cellular B-WICH
      complex through binding to NM1. E2 and NM1 associate via their N-terminal domains
      and this interaction is ATP dependent. The cellular multifunctional protein Brd4
      and beta-actin are also present in the NM1-E2 complex. NM1 downregulation by
      siRNA increases the replication of the BPV1 and HPV5 genomes but does not affect
      HPV18 genome replication. These results suggest that the B-WICH complex may play
      a role in the papillomavirus life cycle through NM1 and E2 protein interaction.

PMID- 29179038
TI  - Molecular evolution and invasion pattern of Cryphonectria hypovirus 1 in Europe:
      Mutation rate, and selection pressure differ between genome domains.
AB  - Understanding virus evolution is a fundamental goal of virology, evolutionary
      biology, and disease epidemiology. We provide a detailed analysis of evolution
      and origin of Cryphonectria hypovirus 1 (CHV1) populations in Europe, based on
      the complete genome sequence of all European subtypes. Phylogenetic analyses
      divided European strains into two closely related clades. Strains of the subtype
      I belong to the first, while strains of the subtypes F1, D and E belong to the
      second clade suggesting that the subtypes F1, D and E are more closely related
      than previously thought. Strains of the subtype F2 appeared to be recombinant;
      subtypes F1/D/E contributed a larger fraction of sequence while subtype I
      contributed a smaller fraction. The p29 was the most variable domain, while the
      replication-associated large ORF B protein was the most conserved domain within
      the CHV1. Low sequence similarity, predominant negative selection and frequent
      recombination characterise the evolution of CHV1.

PMID- 29179039
TI  - Custom Morse taper zirconia abutments: Influence on marginal fit and torque loss
      before and after thermomechanical cycling.
AB  - The use of zirconia abutments has increased because of aesthetics, but sometimes
      customization is necessary and its effect is unclear. This study evaluated the
      marginal fit and torque loss of customized and non-customized aesthetic zirconia
      abutments associated with Morse taper implants before and after thermomechanical
      cycling. Twenty-four implant/abutment/crown sets were divided into three groups
      (N = 8): Zr - non-customized zirconia abutments, Zrc - customized zirconia
      abutments, and Ti - titanium abutments. The ceramic crowns of the upper canines
      were made. All of the abutments were tightened with 15-N.cm torque, and the
      crowns were cemented on the abutments. The misfits and torque loss were measured
      before and after thermomechanical cycling. The marginal fit was evaluated in two
      planes throughout 10 different slices, 30 measurements for each face (i.e.,
      buccal, palatal, mesial and distal) and 120 measurements for each sample. A load
      of 100N, a frequency of 2Hz and 1000,000 cycles with temperature variation of 5
      degrees -55 degrees C were used for thermomechanical cycling. Thermomechanical
      cycling significantly decreased the marginal misfit only with the Zrc (p =
      0.002), and the Ti was significantly different from the Zr and Zrc before and
      after thermomechanical cycling. Thermomechanical cycling did not affect the
      torque losses of the groups, but a significant difference between the Zr and Zrc
      (p = 0.0345) before cycling was noted. Customization of zirconia abutments does
      not significantly affect torque loss and marginal misfit after thermomechanical
      cycling suggesting that they can be safe for clinical utilization.

PMID- 29179040
TI  - Surface integrity and corrosion performance of biomedical magnesium-calcium alloy
      processed by hybrid dry cutting-finish burnishing.
AB  - Biodegradable magnesium-calcium (MgCa) alloy is a very attractive orthopedic
      biomaterial compared to permanent metallic alloys. However, the critical issue is
      that MgCa alloy corrodes too fast in the human organism. Compared to dry cutting,
      the synergistic dry cutting-finish burnishing can significantly improve corrosion
      performance of MgCa0.8 (wt%) alloy by producing a superior surface integrity
      including good surface finish, high compressive hook-shaped residual stress
      profile, extended strain hardening in subsurface, and little change of grain
      size. A FEA model was developed to understand the plastic deformation of MgCa
      materials during burnishing process. The measured polarization curves, surface
      micrographs, and element distributions of the corroded surfaces by burnishing
      show an increasing and uniform corrosion resistance to simulated body fluid.

PMID- 29179041
TI  - Host-pathogen systems for early drug discovery against tuberculosis.
AB  - Tuberculosis (TB) is a global disease causing 1.8 million deaths each year. The
      appearance of drug-resistant strains raised the demand for new anti-mycobacterial
      drugs and therapies, because previously discovered antibiotics are shown to be
      inefficient. Moreover, the number of newly discovered drugs is not increasing in
      proportion to the emergence of drug resistance, which suggests that more
      optimized methodology and screening procedures are required including the
      incorporation of in vivo properties of TB infection. A way to improve efficacy of
      screening approaches is by introducing the use of different host-pathogen systems
      into primary screenings. These include whole cell-based screenings, zebrafish
      larvae-based screenings and the impact of artificial granuloma research on the
      drug discovery process. This review highlights current screening attempts and the
      identified molecular targets and summarizes findings of alternative, not fully
      explored host-pathogen systems for the characterization of anti-mycobacterial
      compounds.

PMID- 29179042
TI  - Discovery of new RNA classes and global RNA-binding proteins.
AB  - The identification of new RNA functions and the functional annotation of
      transcripts in genomes represent exciting yet challenging endeavours of modern
      biology. Crucial insights into the biological roles of RNA molecules can be
      gained from the identification of the proteins with which they form specific
      complexes. Modern interactome techniques permit to profile RNA-protein
      interactions in a genome-wide manner and identify new RNA classes associated with
      globally acting RNA-binding proteins. Applied to a variety of organisms, these
      methods are already revolutionising our understanding of RNA-mediated biological
      processes. Here, we focus on one such approach-Gradient sequencing or Grad-seq
      which has recently guided the discovery of protein ProQ and its associated small
      RNAs as a new domain of post-transcriptional control in bacteria.

PMID- 29179043
TI  - The effect of exercise intensity on joint power and dynamics in ergometer double
      poling performed by cross-country skiers.
AB  - The purpose of this study was to examine the effect of increasing exercise
      intensity on the role of joint powers in ergometer double poling (DP), while
      taking specific dynamic constraints into account. One main question was whether
      lower-body power contribution increased or decreased with increasing intensity.
      Nine male Norwegian national-level cross-country skiers performed ergometer DP at
      low, moderate, high and maximal intensity. Kinematics, and ground (GRF) and
      poling (Fpoling) reaction forces were recorded and used in link segment modeling
      to obtain joint and whole-body dynamics. Joint powers were averaged over the
      cycle, the poling (PP) and recovery (RP) phases. The contribution of these
      average powers was their ratios to cycle average poling power. At all
      intensities, the shoulder (in PP) and hip (mostly in RP) generated most power.
      Averaged over the cycle, lower-body contribution (sum of ankle, knee and hip
      power) increased from ~37% at low to ~54% at maximal intensity (p < .001),
      originating mostly from increased hip contribution within PP, not RP. The
      generation of larger Fpoling at higher intensities demanded a reversal of hip and
      knee moment. This was necessary to appropriately direct the GRF vector as
      required to balance the moment about center of mass generated by Fpoling (control
      of angular momentum). This was reflected in that the hip changed from mostly
      absorbing to generating power in PP at lower and higher intensities,
      respectively. Our data indicate that power-transfer rather than stretch
      shortening mechanisms may occur in/between the shoulder and elbow during PP. For
      the lower extremities, stretch-shortening mechanisms may occur in hip, knee and
      trunk extensors, ensuring energy conservation or force potentiation during the
      countermovement-like transition from body lowering to heightening. In DP
      locomotion, increasing intensity and power output is achieved by increased lower
      body contribution. This is, at least in ergometer DP, partly due to changes in
      joint dynamics in how to handle dynamic constraints at different intensities.

PMID- 29179045
TI  - Reduced recognition and priming in older relative to young adults for incidental
      and intentional information.
AB  - Older adults often show greater implicit/unconscious memory than young adults for
      incidental information that was task-irrelevant during its acquisition.
      Shallow/perceptual encoding by older adults may boost performance on implicit
      tasks that reinstate this type of processing, whereas deeper/conceptual encoding
      by young adults may support greater explicit/conscious memory. To test this,
      young and older participants were exposed to incidental words in a text color
      identification task before the trial-by-trial capture of priming and recognition.
      In Experiments 1-3 priming and recognition were significantly greater in young
      than older adults, providing evidence against age differences in encoding style.
      In Experiments 2-3 older adults were more liberal than young adults in making
      positive recognition judgments to incidental relative to intentional items, even
      though source memory was poor in both groups. Findings pinpoint age differences
      in the utilization of previously incidental versus intentional information on
      different types of task.

PMID- 29179044
TI  - Nicotine as a discriminative stimulus for ethanol use.
AB  - Abused drugs reinforce behavior; i.e., they increase the probability of the
      behavior preceding their administration. Abused drugs can also act as
      discriminative stimuli; i.e., they can set the occasion for responding reinforced
      by another event. Thus, one abused drug could come to set the occasion for the
      use of another and this functional relationship may play a role in polysubstance
      abuse, where common patterns of use could result in this relationship. Here we
      establish nicotine (0.4mg/kg, ip 5-min pre-session) as a discriminative stimulus
      for behavior reinforced by ethanol (0.1ml 8% w/v po, versus food) and determine
      the ability of nicotine (0.02-0.4mg/kg), varenicline (0.1-3.0mg/kg), and ethanol
      (250 and 500mg/kg) to control responding for ethanol. We compare these results to
      those from rats where nicotine signaled food was available (and ethanol was not).
      Nicotine came to function as a discriminative stimulus. Nicotine and varenicline
      produced dose-dependent increases in responding on the nicotine-appropriate lever
      while ethanol produced responding on the vehicle-appropriate lever. Whether this
      responding occurred on the lever that produced ethanol or food access depended on
      the training condition. These results demonstrate that a drug can come to set the
      occasion for use of another and suggest that this behavioral mechanism could play
      an important role in the maintenance of and recovery from polysubstance abuse,
      depending on the pattern of use.

PMID- 29179046
TI  - Enhanced accessibility of ignored neutral and negative items in nonclinical
      dissociative individuals.
AB  - While clinical studies showed paradoxical memory phenomena, including the
      intrusion and amnesia of stressful experiences that are features of dissociation,
      the results of laboratory studies on dissociative individuals' forgetting of
      experimental stimuli through cognitive control varied. Some studies demonstrated
      ineffective inhibition, and others found that dissociative individuals could
      remember fewer trauma words in a divided-attention context. Dissociative
      individuals may utilize superior cognitive disengagement to forget the
      representations. This hypothesis was tested in nonclinical individuals with high,
      medium, and low dissociation proneness. In the study phase, the participants
      learned several lists of experimental words and kept updating working memory by
      remembering the last four items on a list (target) and ignoring those non-target
      items. A recognition test was then conducted. The high dissociation group
      performed better on updating working memory. However, the accessibility of the
      representations of neutral and negative non-target items was elevated.
      Dissociative individuals disengaged attention effectively from items they
      intended to ignore, and the representations of the ignored items were more
      accessible when cues were available.

PMID- 29179047
TI  - A review of numerical models to predict the atmospheric dispersion of
      radionuclides.
AB  - The field of atmospheric dispersion modeling has evolved together with nuclear
      risk assessment and emergency response systems. Atmospheric concentration and
      deposition of radionuclides originating from an unintended release provide the
      basis of dose estimations and countermeasure strategies. To predict the
      atmospheric dispersion and deposition of radionuclides several numerical models
      are available coupled with numerical weather prediction (NWP) systems. This work
      provides a review of the main concepts and different approaches of atmospheric
      dispersion modeling. Key processes of the atmospheric transport of radionuclides
      are emission, advection, turbulent diffusion, dry and wet deposition, radioactive
      decay and other physical and chemical transformations. A wide range of modeling
      software are available to simulate these processes with different physical
      assumptions, numerical approaches and implementation. The most appropriate
      modeling tool for a specific purpose can be selected based on the spatial scale,
      the complexity of meteorology, land surface and physical and chemical
      transformations, also considering the available data and computational resource.
      For most regulatory and operational applications, offline coupled NWP-dispersion
      systems are used, either with a local scale Gaussian, or a regional to global
      scale Eulerian or Lagrangian approach. The dispersion model results show large
      sensitivity on the accuracy of the coupled NWP model, especially through the
      description of planetary boundary layer turbulence, deep convection and wet
      deposition. Improvement of dispersion predictions can be achieved by online
      coupling of mesoscale meteorology and atmospheric transport models. The 2011
      Fukushima event was the first large-scale nuclear accident where real-time
      prognostic dispersion modeling provided decision support. Dozens of dispersion
      models with different approaches were used for prognostic and retrospective
      simulations of the Fukushima release. An unknown release rate proved to be the
      largest factor of uncertainty, underlining the importance of inverse modeling and
      data assimilation in future developments.

PMID- 29179048
TI  - Corrigendum to "Novel application of three-dimensional technologies in a case of
      dismemberment" [Forensic Sci. Int. 270C (2017) 139-145].

PMID- 29179049
TI  - Histological estimation of age at death in amputated lower limbs: Issues of
      disuse, advanced age, and disease in the analysis of pathological bone.
AB  - Histological studies of healed bone tissue following amputation are relatively
      rare in the literature. This study describes the histomorphological features of
      femoral thin sections from six uni- and bi-lateral amputees of documented age and
      sex. Thin sections were cut from the midshaft of both the right and left femora
      from each amputee and analyzed following standard forensic methods for
      histological estimation of age at death from the human femur. The histological
      age at death estimations for the thin sections from amputated bone were
      consistently lower than the actual chronological age of each individual,
      suggesting that the effects of amputation prohibit the effective use of age at
      death estimation methods. The nature of each amputation is unknown, which
      suggests that alternative factors could be responsible for the slowed bone
      turnover seen in the thin sections from the amputated bone. First, it is
      reasonable to assume that the amputations in this sample could have resulted from
      complications of diabetes mellitus rather than trauma so the possible effects on
      bone remodeling due to disease are explored. Second, the mobility of the
      decedents following their amputations is unknown so the histomorphological
      results could be due to disuse osteoporosis.

PMID- 29179050
TI  - First year nursing students use of social media within education: Results of a
      survey.
AB  - INTRODUCTION: Social media rapidly disseminates information but is a
      controversial learning platform in nurse education. This study aimed to explore
      how students viewed the use of Twitter, and other social media, in their first
      year of a nursing degree. AIM: The aim of this study was to evaluate first year
      student nurses' use of social media, before and after commencing a pre
      registration programme, where Twitter was used in a module. METHODOLOGY: A cross
      sectional approach using a descriptive survey was completed. METHODS: An online
      survey, that included Likert scale and open questions, was open for one month in
      2016. SAMPLE: All students on Nursing Undergraduate Degrees, in Adult, Child and
      Mental Health, who were in the first year of their programme were eligible to
      participate. 121 students took part with a response rate of 32%. RESULTS: Most
      students were positive about using social media as they found it an engaging way
      to promote discussion and share information. Students use of Twitter changed in
      the first year with 19.8% using it once or more per week on commencement of the
      programme which increased to 45.5%; other social media platforms remained static.
      Most students (57.8%) understood the purpose of using Twitter although 14%
      reported that it was not used within their module; thus, not all students gained
      experience of using the social media. 81% of students said that using Twitter had
      been beneficial to increase awareness of nursing issues within their course.
      However, there were areas that students found difficult such as time, and not
      knowing what to say. CONCLUSION: The study suggests that teaching about social
      media, and incorporating it into learning activities, may be beneficial for
      students. However, more research into the subject using an experimental design to
      assess changes over time would be useful.

PMID- 29179051
TI  - Differences in pattern of variability for lower extremity kinematics between
      walking and running.
AB  - This study characterizes walking and running patterns in healthy individuals
      using linear and nonlinear methods Seventeen individuals (12 males, 5 females)
      volunteered for the study. 3D kinematic data during walking (WA) and running (RU)
      on a motorized treadmill were captured using reflective markers placed on lower
      body (200Hz). A single 25s trial (5000 data points) was collected for each gait
      task. WA speed was 1.39+/-0.12m/s, whereas RU speed was 2.56+/-0.27m/s. Variables
      of interest included ankle plantar/dorsi flexion, knee flexion/extension, knee
      abduction/adduction, hip flexion/extension, and hip abduction/adduction angles.
      For linear analysis, standard deviation (SD) and coefficient of variation (CV)
      were calculated for the entire time series for both conditions. Nonlinear
      analysis included assessing pattern of regularity of respective kinematic time
      series using approximate entropy (ApEn). Inferential analyses were conducted
      using MANOVA to compare selected dependent measures (p<0.05). SD for knee
      flexion/extension angle (WA=23.34+/-4.17, RU=27.51+/-5.25) and ankle
      plantar/dorsi flexion angle (WA=9.24+/-2.37, RU=12.88+/-2.00) were both greater
      during running. For all other variables, there were no significant differences in
      degree of variability between walking and running (p's>0.05). Running ApEn values
      were greater than walking ApEn values for knee flexion/extension (WA=0.14+/-0.02,
      RU=0.23+/-0.04), knee abduction/adduction (WA=0.18+/-0.07, RU=0.24+/-0.07), hip
      flexion/extension (WA=0.09+/-0.02, RU=0.17+/-0.04), and hip abduction/adduction
      (WA=0.12+/-0.03, RU=0.21+/-0.05). Greater variability was demonstrated during
      running across all joints compared to walking. This suggests that ApEn is more
      sensitive to detecting changes between different gait conditions than standard
      discrete measures of variability (SD).

PMID- 29179052
TI  - Using phone sensors and an artificial neural network to detect gait changes
      during drinking episodes in the natural environment.
AB  - BACKGROUND: Phone sensors could be useful in assessing changes in gait that occur
      with alcohol consumption. This study determined (1) feasibility of collecting
      gait-related data during drinking occasions in the natural environment, and (2)
      how gait-related features measured by phone sensors relate to estimated blood
      alcohol concentration (eBAC). METHODS: Ten young adult heavy drinkers were
      prompted to complete a 5-step gait task every hour from 8pm to 12am over four
      consecutive weekends. We collected 3-axis accelerometer, gyroscope, and
      magnetometer data from phone sensors, and computed 24 gait-related features using
      a sliding window technique. eBAC levels were calculated at each time point based
      on Ecological Momentary Assessment (EMA) of alcohol use. We used an artificial
      neural network model to analyze associations between sensor features and eBACs in
      training (70% of the data) and validation and test (30% of the data) datasets.
      RESULTS: We analyzed 128 data points where both eBAC and gait-related sensor data
      were captured, either when not drinking (n=60), while eBAC was ascending (n=55)
      or eBAC was descending (n=13). 21 data points were captured at times when the
      eBAC was greater than the legal limit (0.08mg/dl). Using a Bayesian regularized
      neural network, gait-related phone sensor features showed a high correlation with
      eBAC (Pearson's r>0.9), and >95% of estimated eBAC would fall between -0.012 and
      +0.012 of actual eBAC. CONCLUSIONS: It is feasible to collect gait-related data
      from smartphone sensors during drinking occasions in the natural environment.
      Sensor-based features can be used to infer gait changes associated with elevated
      blood alcohol content.

PMID- 29179053
TI  - Rapid start-up of a bioelectrochemical system under alkaline and saline
      conditions for efficient oxalate removal.
AB  - This study examined a new approach for starting up a bioelectrochemical system
      (BES) for oxalate removal from an alkaline (pH > 12) and saline (NaCl 25 g/L)
      liquor. An oxalotrophic biofilm pre-grown aerobically onto granular graphite
      carriers was used directly as both the microbial inoculum and the BES anode. At
      anode potential of +200 mV (Ag/AgCl) the biofilm readily switched from using
      oxygen to graphite as sole electron acceptor for oxalate oxidation. BES
      performance was characterised at various hydraulic retention times (HRTs, 3-24
      h), anode potentials (-600 to +200 mV vs. Ag/AgCl) and influent oxalate (25 mM)
      to acetate (0-30 mM) ratios. Maximum current density recorded was 363 A/m3 at 3 h
      HRT with a high coulombic efficiency (CE) of 70%. The biofilm could concurrently
      degrade acetate and oxalate (CE 80%) without apparent preference towards acetate.
      Pyro-sequencing analysis revealed that known oxalate degraders Oxalobacteraceae
      became abundant signifying their role in this novel bioprocess.

PMID- 29179054
TI  - Effects of co-digestion of cucumber residues to corn stover and pig manure ratio
      on methane production in solid state anaerobic digestion.
AB  - This study investigated the performance of co-digesting cucumber residues, corn
      stover, and pig manure at different ratios. Microbial community structure was
      analyzed to elucidate functional microorganism contributing to methane production
      during co-digestion. Results show that mixing cucumber residues with pig manure
      and corn stover could significantly improved methane yields 1.27-3.46 times
      higher than mono-feedstock. The methane yields decreased with the cucumber
      residues increasing when the pig manure ratio was fixed at 4 and 3, and was
      opposite at ratio 5. The optimal mixture ratio was T2 with the highest methane
      yield (305.4 mL/g VS) and co-digestion performance index (1.97). The main
      microbiological community in T2 was bacteria of Firmicutes (44.6%), Bacteroidetes
      (32.5%), Synergistetes (3.8%) and archaea of Methanosaeta (37.1%),
      Methanospirillum (18.2%). The mixture ratios changed the microbial community
      structures. The adding proportion of cucumber residues changed the community
      composition of the archaea, especially the proportion of Methanosaeta.

PMID- 29179055
TI  - Postmortem biochemical investigation results in situations of fatal mechanical
      compression of the neck region.
AB  - Biochemical investigations performed in cases of mechanical asphyxia have
      provided diverging information over time. The purpose of the study presented
      herein was threefold: to investigate the postmortem stability of a series of
      molecules (thyroglobulin, iodothyronines, calcitonin, and parathyroid hormone) in
      blood after death, to determine the same molecules in a series of cases of
      suicidal hangings for which antemortem serum samples were available, and to
      measure the same molecules in postmortem serum obtained from different sampling
      sites thereby evaluating the distribution of these molecules in the specific
      samples. Preliminary results indicated postmortem stability of thyroglobulin,
      calcitonin, and parathyroid hormone levels, decreasing total and free T4 levels,
      and increasing total and free T3 concentrations. Our findings also showed that
      antemortem mechanical force applied to the neck region (hanging cases) may be
      accompanied by increased thyroglobulin in peripheral (femoral) blood, though a
      certain number of cases with nonincreased thyroglobulin levels may be observed.
      Lastly, our results revealed that hanging, manual, and ligature strangulation
      cases may be accompanied by increased thyroglobulin, total T3, and free T3 values
      in postmortem serum specimens obtained from blood sampled at different sampling
      sites, even in the absence of microscopically identified thyroid gland tissue
      damage. Such increases are more constant and important in arterial and venous
      blood samples obtained from sampling sites located in close vicinity of the
      thyroid gland.

PMID- 29179056
TI  - Cortical morphometry and cognition in very preterm and term-born children at
      early school age.
AB  - Very preterm birth influences brain development and may result in alterations of
      cortical morphometry. These structural alterations may interact with cognitive
      development. The aim of the present study was to investigate the structure
      function relationship in school-aged very preterm and term-born control children.
      A comprehensive neuropsychological test battery was administered to 41 very
      preterm (<32 weeks of gestation) and 30 term-born control children aged seven to
      twelve years. The automated method FreeSurfer was used to obtain cortical
      thickness and cortical surface area measures from T1-weighted MRI images.
      Regional cortical thickness differed between groups but differences disappeared
      when controlling for age. Global cortical thickness differed between groups in
      the right hemisphere (very preterm children>controls). No group differences
      occurred for cortical surface area. The relationship between cortical morphometry
      and cognition differed between very preterm and control children. In very preterm
      children, some cognitive domains correlated positively and others negatively with
      regional cortical thickness and cortical surface area. Our findings contribute to
      the understanding of the structure-function relationship in very preterm children
      and their term-born peers. They add to the notion that this relationship varies
      depending on the brain region and the cognitive function in question and suggest
      developmental differences between very preterm and term-born children.

PMID- 29179057
TI  - Digit ratio (2D:4D) and coronary artery disease in north Chinese women.
AB  - BACKGROUND: Digit ratio (2D:4D) is fixed in utero and affected by fetal sex
      steroids. It has been proposed as a putative biomarker of certain hormone-
      related adult life traits and diseases. Several evidence suggest that 2D:4D ratio
      may correlate with cardiovascular disease risk (e.g., coronary artery disease).
      AIMS: To investigate whether there is a possible relationship between digit ratio
      (especially 2D:4D ratio) and coronary artery disease (CAD), and age at CAD in
      north Chinese women. METHODS: Photographs of the two hands of 303 females
      (controls: 194; patients: 109) were collected. Left hand, right hand and right
      minus left hand (Dr-l) digit ratio were analyzed and compared. RESULTS: The mean
      values of digit ratio in patients with CAD were lower than controls for each
      hand. Significant differences of 2D:4D (left and right hand: P<0.01), 2D:5D (left
      hand: P<0.01; right hand: P<0.05) and 3D:4D (left hand: P<0.01) were found
      between two groups. There were no associations between 2D:4D ratio and age at CAD
      on both hands. CONCLUSION: Decreased digit ratio (especially 2D:4D ratio) may
      suggest a higher prenatal testosterone (lower prenatal oestrogen) exposure in
      north Chinese women with coronary artery disease.

PMID- 29179058
TI  - Laparoscopic ovarian biopsy pick-up method for goats.
AB  - Biopsy pick-up (BPU) has been considered a safe method to harvest ovarian
      fragments from live animals. However, no studies have been reported on the use of
      BPU to collect in vivo ovarian tissue in goats. The goals of this study were: (i)
      to test different biopsy needle sizes to collect ovarian tissue in situ using the
      BPU method (Experiment 1), and (ii) to study ovarian tissue features such as
      preantral follicle density, morphology, class distribution, and stromal cell
      density in ovarian fragments obtained in vivo through a laparoscopic BPU method
      (Experiment 2). In Experiment 1, goat ovaries (n = 20) were collected in a
      slaughterhouse and subjected to in situ BPU. Three needles (16, 18, and 20G) were
      tested. In Experiment 2, the most efficient biopsy needle from Experiment 1 was
      used to perform laparoscopic BPU in goats (n = 8). In Experiment 1, the recovery
      rate was greater (P < 0.05; range 50-62%) with 16G and 18G needles than the 20G
      (17%) needle. The mean weight of ovarian fragments collected by the 16G needle
      was greater (P < 0.05) than the 18G and the 20G needle. In Experiment 2, 62
      biopsy attempts were performed and 52 ovarian fragments were collected (90%
      success rate). Overall, 2054 preantral follicles were recorded in 5882
      histological sections analyzed. Mean preantral follicular density was 28.4 +/-
      1.3 follicles per cm2. The follicular density differed (P < 0.05) among animals
      and ovarian fragments within the same animal. The mean stromal cell density in
      the ovarian fragments was 37.1 +/- 0.5 cells per 2500 MUm2, and differed (P <
      0.05) among animals. Moreover, preantral follicle density and stromal cell
      density were associated (P < 0.001). The percentage of morphologically normal
      follicles was 70.1 +/- 1.2, and differed (P < 0.05) among animals. The majority
      (79%) of the morphologically normal follicles was classified as primordial
      follicles, and differed (P < 0.05) among animals and between ovaries. In summary,
      a laparoscopic BPU method has been developed to harvest ovarian tissue in vivo
      with a satisfactory success rate in goats. Furthermore, this study described for
      the first time that goat ovarian biopsy fragments have a high heterogeneity in
      follicular density, morphology, class distribution, and stromal cell density.

PMID- 29179059
TI  - Determination of recombinant Interferon-alpha2 in E. coli periplasmic extracts by
      reversed-phase high-performance liquid chromatography.
AB  - Reversed-phase high-performance liquid chromatography (RP-HPLC) has been used to
      analyze Interferon alpha-2 (IFN-alpha2) as a pure protein or as a pharmaceutical
      preparation: a method for analyzing periplasmic IFN-alpha2 directly in osmotic
      shock extract has, however, never been reported. This work describes an RP-HPLC
      methodology for the qualitative and quantitative analysis of human IFN-alpha2a
      and IFN-alpha2b directly in bacterial periplasmic extracts or in purified
      preparations. The analytical method has been set up and validated for accuracy,
      precision, linearity, sensitivity and specificity. A recovery test indicated an
      average bias of ~1%, intra-day and inter-day quantitative determinations
      presented relative standard deviations always<=5%, while the working sensitivity
      was of ~0.3MUg of IFN-alpha2 (RSD=5%). The method proved to be suitable for
      detecting and quantifying also glycosylated and oxidized forms and N
      methionylated IFN-alpha2 molecules, it was, however, not able to distinguish
      between IFN-alpha2a and IFN-alpha2b. This rapid methodology allows the
      application of RP-HPLC as a powerful tool to monitor the production yield and
      quality of IFN-alpha2 in osmotic shock fluids, right after, or even during the
      fermentation process.

PMID- 29179060
TI  - Development, validation, and application of an UPLC-MS/MS method for
      norvancomycin analysis in human blood plasma.
AB  - Norvancomycin (NVCM) is used in treating patients with infections caused by drug
      resistant gram-positive bacteria. The NVCM plasma concentration varies greatly
      among individuals. To avoid the adverse drug reactions and prevent the presence
      of drug-resistant bacteria, the routine monitoring of NVCM in blood plasma was
      strongly recommended. However, there were few methods for plasma NVCM analysis.
      To the best of our knowledge, this is the first validated ultra performance
      liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for plasma
      NVCM analysis. The ion transition for NVCM was m/z 718.5>144.1. The flow rate was
      0.4mL/min with a run time of 3.5min. The calibration range of the UPLC-MS/MS
      method was 1-100mg/L. The intra-day and inter-day inaccuracy and imprecision were
      -7.39%-10.27% and less than 11.55%. The internal standard (IS) normalized
      recovery and matrix factor were 68.24%-78.24% and 94.53% to 115.80%,
      respectively. The coefficient variations of IS normalized recovery and matrix
      factor were less than 11.24% and 9.14%. Age, body weight, and creatinine
      clearance affect NVCM plasma concentrations in 20 patients. Further studies are
      warranted to confirm the results.

PMID- 29179061
TI  - A UPLC-MS/MS method for simultaneous determination of 1-deoxynojirimycin and N
      methyl-1-deoxynojirimycin in rat plasma and its application in pharmacokinetic
      and absolute bioavailability studies.
AB  - A specific, sensitive, rapid, precise, and reliable UPLC-MS/MS-based method was
      designed for the first time for the simultaneous determination of 1
      deoxynojirimycin (DNJ) and N-methyl-1-deoxynojirimycin (N-CH3-DNJ) in rat plasma.
      Miglitol was served as the internal standard (IS). An MN-NUCLEODUR HILIC column
      was assessed to separate the two compounds by isocratic elution using
      acetonitrile: water with 0.05% formic acid and 6.5mM ammonium acetate (72:28,
      v/v) at a flow rate of 0.4mL/min. A triple quadrupole mass spectrometer was
      operated in the positive ionization mode using multiple reaction monitoring
      (MRM), and it was employed to determine transitions of m/z 164.1->110.1, 178.1
      >100.1, and 208.1->146.1 for DNJ, N-CH3-DNJ, and IS, respectively. The method of
      the two constituents was validated and the results were acceptable. The absolute
      bioavailability of DNJ and N-CH3-DNJ in rats was 50+/-9% and 62+/-24%,
      respectively. The method was then successfully used for the first time to study
      the pharmacokinetic behavior and absolute bioavailability of DNJ and N-CH3-DNJ in
      rats after intravenous (10mg/kg) and oral administration (80mg/kg). The results
      of this study might provide more information on preclinical pharmacokinetics and
      a solid basis for assessing the clinical efficacy of DNJ and N-CH3-DNJ.

PMID- 29179062
TI  - An effective method for preparation of high-purity pelargonidin-3-O-glucoside
      from strawberry and its protective effect on cellular oxidative stress.
AB  - Accumulating evidence indicates that consumption of berries may exert beneficial
      effects against oxidative stress mediated diseases. Pelargonidin-3-O-glucoside
      (Pg3G), a bioactive ingredient in strawberry, has been reported to possess a
      potent antioxidant capacity. This study was therefore designed to develop an
      effective method to prepare pure Pg3G from strawberry and investigate its
      protective effect against H2O2-induced oxidative stress. According to our
      results, Pg3G occupied 85.55% of total anthocyanin content in strawberry. 240mg
      of Pg3G with the purity of 97.26% was finally isolated from 320g of strawberry
      lyophilized powder (SLP) by combination of AB-8 macroporous resin and high-speed
      counter-current chromatography (HSCCC) technologies. Further study unveiled that
      Pg3G significantly inhibited H2O2-induced ROS generation, GSH depletion and
      mitochondrial dysfunction, thereby ameliorating H2O2-induced oxidative stress.
      Overall, this study suggests that pelargonidin-3-O-glucoside can be used as a
      natural bioactive agent to prevent cellular oxidative stress.

PMID- 29179063
TI  - Simultaneous determination of phenolic acids and diterpenoids and their
      comparative pharmacokinetic study in normal and acute blood stasis rats by UFLC
      MS/MS after oral administration of Guan-Xin-Shu-Tong capsules.
AB  - Guan-Xin-Shu-Tong capsules are one of the well-known and first-line Chinese
      traditional herbal formula for treating coronary heart disease. A validated and
      sensitive method via ultra fast liquid chromatography-tandem mass spectrometry
      (UFLC-MS/MS) was established to simultaneously determinate five phenolic acids
      and four diterpenoids in rats in order to investigate their pharmacokinetic
      profiles firstly. Analytes were extracted by ethyl acetate and determined via
      multiple reaction monitoring mode in both positive and negative ion modes. The
      values for limit of quantification were in range of 0.025-1.250ng/ml. Inter- and
      intra-day precisions were no more than 10.9% with accuracy of -11.0%-10.6%,
      meanwhile the stable and suitable extraction recoveries were also obtained. And
      finally such excellent method was used to compare the pharmacokinetics of nine
      compounds in normal and acute blood stasis rats after oral administration of Guan
      Xin-Shu-Tong capsules.

PMID- 29179065
TI  - Reaction profiling of a set of acrylamide-based human tissue transglutaminase
      inhibitors.
AB  - The major function of the enzyme human tissue transglutaminase (TG2) is the
      crosslinking of proteins via a transamidation between the gamma-carboxamide of a
      glutamine and the epsilon-amino group of a lysine. Overexpression of TG2 can lead
      to undesirable outcomes and has been linked to conditions such as fibrosis,
      celiac disease and neurodegenerative diseases. Accordingly, TG2 is a tempting
      drug target. The most effective TG2 inhibitors to date are small-molecule
      peptidomimetics featuring electrophilic warheads that irreversibly modify the
      active site catalytic cysteine (CYS277). In an effort to facilitate the design of
      such TG2 inhibitors, we undertook a quantum mechanical reaction profiling of the
      Michael reaction between a set of six acrylamide-based known TG2 inhibitors and
      the TG2 CYS277. The inhibitors were docked into the active site and the
      coordinates were refined by MD simulations prior to modelling the covalent
      modification of the CYS277 thiolate. The results of QM/MM MD umbrella sampling
      applied to reaction coordinates driving the Michael reaction are presented for
      two approximations of the Michael reaction: a concerted reaction (simultaneous
      thiolate attack onto the acrylamide warhead and pronation from the adjacent
      HIS335) and a two-stage reaction (consecutive thiolate attack and protonation).
      The two-stage approximation of the Michael reaction gave the better results for
      the evaluation of acrylamide-based potential TG2 inhibitors in silico. Good
      correlations were observed between the experimental TG2 IC50 data and the
      calculated activation energies over the range 0.0061-6.3MUM (three orders of
      magnitude) and we propose that this approach may be used to evaluate acrylamide
      based potential TG2 inhibitors.

PMID- 29179064
TI  - A simple and highly sensitive UPLC-ESI-MS/MS method for the simultaneous
      quantification of nicotine, cotinine, and the tobacco-specific carcinogens N'
      nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in serum
      samples.
AB  - According to the World Health Organization, the consumption of tobacco products
      is the single largest cause of preventable deaths in the world, exceeding the
      total aggregated number of deaths caused by diseases such as AIDS, tuberculosis,
      and malaria. An important element in the evaluation of the health risks
      associated with the consumption of tobacco products is the assessment of the
      internal exposure to the tobacco constituents responsible for their addictive
      (e.g. nicotine) and carcinogenic (e.g. N-nitrosamines such as NNN and NNK)
      properties. However, the assessment of the serum levels of these compounds is
      often challenging from an analytical standpoint, in particular when limited
      sample volumes are available and low detection limits are required. Currently
      available analytical methods often rely on complex multi-step sample preparation
      procedures, which are prone to low analyte recoveries and ex-vivo contamination
      due to the ubiquitous nature of these compounds as background contaminants. In
      order to circumvent these problems, we report a facile and highly sensitive
      method for the simultaneous quantification of nicotine, cotinine, NNN, and NNK in
      serum samples. The method relies on a simple "one pot" liquid-liquid extraction
      procedure and isotope dilution ultra-high pressure (UPLC) hydrophilic interaction
      liquid chromatography (HILIC) coupled with tandem mass spectrometry. The method
      requires only 10MUL of serum and presents a limit of quantification of 0.02nmol
      (3000pg/mL) nicotine, 0.6pmol (100pg/mL) cotinine, 0.05pmol NNK (10pg/mL), and
      0.06pmol NNN (10pg/mL), making it appropriate for pharmacokinetic evaluations.

PMID- 29179066
TI  - Rice yield in response to climate trends and drought index in the Mun River
      Basin, Thailand.
AB  - Rice yields in Thailand are among the lowest in Asia. In northeast Thailand where
      about 90% of rice cultivation is rain-fed, climate variability and change affect
      rice yields. Understanding climate characteristics and their impacts on the rice
      yield is important for establishing proper adaptation and mitigation measures to
      enhance productivity. In this paper, we investigate climatic conditions of the
      past 30years (1984-2013) and assess the impacts of the recent climate trends on
      rice yields in the Mun River Basin in northeast Thailand. We also analyze the
      relationship between rice yield and a drought indicator (Standardized
      Precipitation and Evapotranspiration Index, SPEI), and the impact of SPEI trends
      on the yield. Our results indicate that the total yield losses due to past
      climate trends are rather low, in the range of <50kg/ha per decade (3% of actual
      average yields). In general, increasing trends in minimum and maximum
      temperatures lead to modest yield losses. In contrast, precipitation and SPEI-1,
      i.e. SPEI based on one monthly data, show positive correlations with yields in
      all months, except in the wettest month (September). If increasing trends of
      temperatures during the growing season persist, a likely climate change scenario,
      there is high possibility that the yield losses will become more serious in
      future. In this paper, we show that the drought index SPEI-1 detects soil
      moisture deficiency and crop stress in rice better than precipitation or
      precipitation based indicators. Further, our results emphasize the importance of
      spatial and temporal resolutions in detecting climate trends and impacts on
      yields.

PMID- 29179067
TI  - How wildfire risk is related to urban planning and Fire Weather Index in SE
      France (1990-2013).
AB  - Wildfires burn >450,000ha of forest every year in Euro-Mediterranean countries.
      Many fires originate in the Wildland Urban Interface (WUI) where housing density
      and weather conditions affect fire occurrence. Housing density is determined by
      long term land use policies while weather conditions evolve quickly. The first
      objective was to quantify the impacts of land use policy on WUI characteristics
      and fire risk in SE France during 1990-2012. The second objective was to quantify
      how Fire Weather Index (FWI) is related to fire occurrence. WUI was mapped from
      1990, 1999, and 2012 building layers and crossed with a NDVI derived vegetation
      layer. In all, 12 WUI categories were derived: 4 building density classes and 3
      vegetation layers. The I87 FWI was based on daily temperature, wind speed,
      relative humidity and soil water content. Despite a 30% increase in the number of
      new buildings, WUI area increased by only 5% as new housing filled in open space
      in existing WUI area. This trend can be linked to national level urban planning
      legislation and forest fire protection laws. Major driver variables determining
      housing location were aspect, slope, and distance to city centers. Fire frequency
      and burned area were nonlinearly related to FWI: 73% of the 99 fires occurred
      during weeks with FWI values >=90 even though these accounted for only 44% of all
      weeks. Burned area was even more sensitive to FWI since 97% of total burned area
      occurred during weeks with mean FWI values >=90. All days with burned areas
      >100ha had FWI values >150. The study demonstrated that WUI legislation can be an
      efficient tool to limit WUI fire risk. FWI results suggest the predicted increase
      in extreme summer heat events with global warming could increase burned area as
      firefighting resources are stretched beyond capacity.

PMID- 29179069
TI  - Renewable energy powered membrane technology: Impact of pH and ionic strength on
      fluoride and natural organic matter removal.
AB  - Real water pH and ionic strength vary greatly, which influences the performance
      of membrane processes such as nanofiltration (NF) and reverse osmosis (RO).
      Systematic variation of pH (3-12) and ionic strength (2-10g/L as total dissolved
      solids (TDS)) was undertaken with a real Tanzanian water to investigate how water
      quality affects retention mechanisms of fluoride (F) and natural organic matter
      (NOM). An autonomous solar powered NF/RO system driven by a solar array simulator
      was supplied with constant power from a generator. An open NF (NF270) and a
      brackish water RO (BW30) membrane were used. A surface water with a very high F
      (59.7mg/L) and NOM (110mgC/L) was used. Retention of F by NF270 was <20% at pH
      <6, increased to 40% at pH6, and 60-70% at pH7-12, indicating a dominance of
      charge repulsion while being ineffective in meeting the guideline of 1.5mg/L.
      Increase in ionic strength led to a significant decline in retention of F (from
      70 to 50%) and electrical conductivity (from 60 to 10%) by NF270, presumably due
      to charge screening. In contrast, BW30 retained about 50% of F at pH3, >80% at
      pH4, and about 99% at pH >5, due to the smaller pore size and hence a more
      dominant size exclusion. In consequence, only little impact of ionic strength
      increase was observed for BW30. The concentration of NOM in permeates of both
      NF270 and BW30 were typically <2mg/L. This was not affected by pH or ionic
      strength due to the fact that the bulk of NOM was rejected by both membranes
      through size exclusion. The research is carried out in the context of providing
      safe drinking water for rural and remote communities where infrastructure is
      lacking, and water quality varies significantly. While other studies focus on
      energy fluctuations, this research emphasises on feed water quality that affects
      system performance and may alter due to a number of environmental factors.

PMID- 29179068
TI  - Persistent organic pollutants (POPs) in blood and blubber of common bottlenose
      dolphins (Tursiops truncatus) at three northern Gulf of Mexico sites following
      the Deepwater Horizon oil spill.
AB  - Common bottlenose dolphins (Tursiops truncatus), including those impacted by the
      2010 Deepwater Horizon (DWH) oil spill, inhabit the coastal and estuarine waters
      of the northern Gulf of Mexico (GoM). In response to the spill, dolphin health
      assessments conducted in Barataria Bay, Louisiana - a site that experienced heavy
      and prolonged oiling - uncovered a high prevalence of health abnormalities and
      individuals in poor body condition. Although the health effects observed were
      suggestive of petroleum toxicity, a lack of pre-spill information regarding
      dolphin health raises the possibility that other environmental factors may have
      contributed to the adverse health of dolphins in this oil-impacted area. To
      assess how exposure to other environmental pollutants may affect the health of
      northern GoM dolphin populations impacted by the DWH oil spill, a suite of 69
      persistent organic pollutants (POPs), including PCBs, PBDEs and organochlorine
      pesticides, was determined in blood and a subset of blubber samples collected
      during health assessments of 145 bottlenose dolphins at three GoM sites: two oil
      impacted sites - Barataria Bay, LA (BB), and Mississippi Sound, MS (MS) and an
      unimpacted reference site - Sarasota Bay, FL (SB). Overall, levels of POPs at all
      three sites appeared comparable or lower than concentrations previously reported
      for coastal bottlenose dolphin populations outside of the northern GoM. POP
      levels measured in BB dolphins were also comparable or lower than those measured
      at the unimpacted reference site (SB) within the northern GoM. Additionally, the
      relationship between blubber and blood contaminant levels in a smaller subset of
      BB and SB suggests that BB animals were not experiencing elevated blood
      contaminant concentrations as a result of their poor body condition.
      Cumulatively, these results suggest that background levels of POPs measured are
      unlikely to produce the health abnormalities previously reported for BB dolphins.

PMID- 29179070
TI  - Biochar modulates heavy metal toxicity and improves microbial carbon use
      efficiency in soil.
AB  - Soil organic carbon is essential to improve soil fertility and ecosystem
      functioning. Soil microorganisms contribute significantly to the carbon
      transformation and immobilisation processes. However, microorganisms are
      sensitive to environmental stresses such as heavy metals. Applying amendments,
      such as biochar, to contaminated soils can alleviate the metal toxicity and add
      carbon inputs. In this study, Cd and Pb spiked soils treated with macadamia
      nutshell biochar (5% w/w) were monitored during a 49days incubation period.
      Microbial phospholipid fatty acids (PLFAs) were extracted and analysed as
      biomarkers in order to identify the microbial community composition. Soil
      properties, metal bioavailability, microbial respiration, and microbial biomass
      carbon were measured after the incubation period. Microbial carbon use efficiency
      (CUE) was calculated from the ratio of carbon incorporated into microbial biomass
      to the carbon mineralised. Total PLFA concentration decreased to a greater extent
      in metal contaminated soils than uncontaminated soils. Microbial CUE also
      decreased due to metal toxicity. However, biochar addition alleviated the metal
      toxicity, and increased total PLFA concentration. Both microbial respiration and
      biomass carbon increased due to biochar application, and CUE was significantly
      (p<0.01) higher in biochar treated soils than untreated soils. Heavy metals
      reduced the microbial carbon sequestration in contaminated soils by negatively
      influencing the CUE. The improvement of CUE through biochar addition in the
      contaminated soils could be attributed to the decrease in metal bioavailability,
      thereby mitigating the biotoxicity to soil microorganisms.

PMID- 29179071
TI  - Biochar decreased the bioavailability of Zn to rice and wheat grains: Insights
      from microscopic to macroscopic scales.
AB  - Zn deficiency is a critical problem for many crops and human populations
      worldwide. Soil biochar amendment has recently been promoted as a sustainable
      agricultural practice. However, its effect on the bioavailability of
      micronutrients (especially Zn) to crops has not been fully addressed. This study
      investigated the impact of long-term biochar application in soils on Zn
      bioavailability to rice and wheat, using field experiments, and batch
      sorption/desorption experiments, in combination with extended X-ray absorption
      fine structure spectroscopy (EXAFS). In field soils biochar amendment increased
      total Zn content, but significantly decreased CaCl2-extractable Zn
      concentrations. Intriguingly, the uptake of Zn to wheat and rice grains was
      decreased. At high biochar application rates of 124 and 270t/ha the Zn
      concentrations in wheat grains (36.6 and 37.5mg/kg) reached a deficient level,
      lower than the recommended concentration of 45mg/kg. The batch experiments showed
      that biochar application at a cumulative rate of 10.5, 15.8, 31.5, 124, and
      270t/ha significantly increased soil pH and soil organic matter (SOM) content,
      resulting in greater sorption and lower desorption of Zn. The EXAFS results
      demonstrated that the main forms of sorbed Zn were outer-sphere Zn complexes, Zn
      illite, Zn-kaolinite and Zn-OM. The proportion of Zn-OM increased with increasing
      biochar application rates, suggesting that higher SOM might be more effective in
      immobilizing Zn and thus decreasing the Zn bioavailability. These results on the
      microscopic and macroscopic scales improved our understanding of the Zn
      bioavailability to crops, and raised potential concerns on the Zn deficiency in
      agricultural soils with long-term biochar application.

PMID- 29179072
TI  - Anaerobic digestion coupled with digestate injection reduced odour emissions from
      soil during manure distribution.
AB  - This work aimed to measure the odour impact of untreated cow and pig slurries and
      treated (digestate and liquid fraction of digestate) manures when they were used
      on soil at a field scale, while also testing different spreading methods, i.e.
      surface vs. injection. Five experiments were performed in 2012-2016 on different
      farms. Odours were quantitatively (specific odour emission rate - SOER) (OUEm-2h
      1) measured by using dynamic olfactometry and qualitatively, i.e. to obtain an
      "odour fingerprint", by using an electronic nose (EN). Anaerobic digestion was
      effective in allowing the reduction of potential odour emission from digestates,
      so that when they were dosed on soil, odours emitted were much lower than those
      from soils on which untreated slurries were used. Slurries/digestate injection
      reduced much more odour emitted by soils so that SOER tended to become more
      similar to that of the control (untreated soil) although the odours were slightly
      greater. Odour fingerprint data indicated that there was a direct correlation
      between SOER and odour fingerprints. This was due to the ability of EN to detect
      ammonia, S-compounds and methane that were (the first two mainly), also,
      responsible for odours. Very good regression was found for Log SOER and EN by
      using a Partial Least Square (PLS) approach (R2=0.73; R2cv=0.66; P<0.01) for
      matrices used to fertilize soils in lab tests. Unfortunately, regression was not
      so good when odour data from field experiments on soil were used, so that EN
      cannot be proposed to replace olfactometry. EN fingerprints for control (Blank)
      and injected organic matrices were virtually identical, due to the creation of
      cavities in the soil during the injection that decreased the treated surface.
      Anaerobic digestion and subsequent digestate injection allowed us to reduce odour
      impact, avoiding annoyance to local inhabitants.

PMID- 29179073
TI  - Identifying change in spatial accumulation of soil salinity in an inland river
      watershed, China.
AB  - Soil salinity accumulation is strong in arid areas and it has become a serious
      environmental problem. Knowledge of the process and spatial changes of
      accumulated salinity in soil can provide an insight into the spatial patterns of
      soil salinity accumulation. This is especially useful for estimating the spatial
      transport of soil salinity at the watershed scale. This study aimed to identify
      spatial patterns of salt accumulation in the top 20cm soils in a typical inland
      watershed, the Sangong River watershed in arid northwest China, using
      geostatistics, spatial analysis technology and the Lorenz curve. The results
      showed that: (1) soil salt content had great spatial variability (coefficient
      variation >1.0) in both in 1982 and 2015, and about 56% of the studied area
      experienced transition the degree of soil salt content from one class to another
      during 1982-2015. (2) Lorenz curves describing the proportions of soil salinity
      accumulation (SSA) identified that the boundary between soil salinity migration
      and accumulation regions was 24.3m lower in 2015 than in 1982, suggesting a
      spatio-temporal inequality in loading of the soil salinity transport region,
      indicating significant migration of soil salinity from the upstream to the
      downstream watershed. (3) Regardless of migration or accumulation region, the
      mean value of SSA per unit area was 0.17kg/m2 higher in 2015 than 1982 (p<0.01)
      and the increasing SSA per unit area in irrigated land significantly increased by
      0.19kg/m2 compared with the migration region. Dramatic accumulation of soil
      salinity in all land use types was clearly increased by 0.29kg/m2 in this
      agricultural watershed during the studied period in the arid northwest of China.
      This study demonstrates the spatial patterns of soil salinity accumulation, which
      is particularly useful for estimating the spatial transport of soil salinity at
      the watershed scale.

PMID- 29179074
TI  - Atmospheric CO2 capture for the artificial photosynthetic system.
AB  - The aim of these studies is to evaluate the ambient CO2 capture abilities of the
      membrane contactor system in the same conditions as leafs, such as ambient
      temperature, pressure and low CO2 concentration, where the only driving force is
      the concentration gradient. The polysulfone membrane employed was made by a phase
      inversion process and characterized by ESEM micrographs which were used to
      determine the thickness, asymmetry and pore size. Besides, the porosity of the
      membrane was measured from the membrane and polysulfone density correlation and
      the hydrophobicity was analyzed by contact angle measurements. Moreover, the
      compatibility of membrane and absorbent was evaluated, in order to exclude
      wetting issues by meaning of swelling, dynamic contact angle and AFM analysis.
      The prepared membranes were introduced into a cross flow module and used as
      contactors between CO2 and the absorbing media, a potassium hydroxide solution.
      The influence of the membrane thickness, absorbent stirring rate, solution pH and
      absorption time on CO2 capture were evaluated. Absorbent solution stirring rate
      showed no statistically significant influence on absorption. We observed a non
      linear correlation between the capture rate and the increase of absorbent
      solution pH as well as absorption time. The results showed that the efficiency of
      our CO2 capture system is similar to stomatal carbon dioxide assimilation rate,
      achieving stable value of 20MUmol/m2.s after 1h of experiment.

PMID- 29179075
TI  - Manure management and public health: Sanitary and socio-economic aspects among
      urban livestock-keepers in Cambodia.
AB  - Livestock manure is a valuable source of nutrients for crop production, but can
      also pose a public health hazard and have negative environmental impacts. This
      study investigated manure management practices among urban and peri-urban
      livestock keepers in Cambodia, to identify risk behaviours and socio-economic
      aspects associated with the handling of manure. A survey including 204 households
      was conducted, using a structured questionnaire with questions on demographics,
      socio-economic characteristics and household practices related to manure
      management. Faecal samples were obtained from pig pens and pig manure storage
      units for analysis of the potential zoonotic pathogens Salmonella enterica
      (Polymerase Chain Reaction (PCR)), Ascaris suum and Trichuris suis (McMaster
      flotation technique). The survey revealed a difference in management between
      cattle and pig manure. Cattle manure was most commonly used as fertiliser for
      crop production (66%) (p<0.001), whereas pig manure was most commonly dumped in
      the environment (46%) (p<0.001). Logistic regression models showed that
      households with a lower socio-economic position were more likely to dump pig
      manure (p<0.001), with scarcity of agricultural land (p<0.001) and lack of carts
      for transportation of manure (p<0.01) being identified as contributing factors.
      Salmonella enterica was detected in 9.7% of manure samples, while Ascaris suum
      and Trichuris suis were detected in 1.6% and 2.4% of the samples, respectively.
      The results presented in this study indicate that manure management by urban and
      peri-urban households may pose a public health threat and an environmental
      hazard. There is evidently a need for further knowledge support to the livestock
      keepers to promote good management practices.

PMID- 29179076
TI  - Urinary concentrations of parabens and reproductive parameters in young men.
AB  - Parabens are a group of alkyl esters of p-hydroxybenzoic acid that are commonly
      added to personal care products, cosmetics, pharmaceuticals and beverage and food
      processing as antimicrobial preservatives. Parabens have been reported to show
      estrogenic effects and affect male reproduction function in animal models, but
      human epidemiologic studies are still scarce. The objective of this study was to
      examine associations between urinary concentrations of parabens and semen quality
      and reproductive hormone levels. This was a cross-sectional study with 215 young
      university students (18-23years old) recruited between 2010 and 2011 in Southern
      Spain (Murcia Region). All men provided a urine, blood and semen sample on a
      single day. Urinary paraben concentrations (methylparaben, ethylparaben,
      propylparaben and butylparaben) were measured by dispersive liquid-liquid
      microextraction and ultra-high performance liquid chromatography with tandem mass
      spectrometry detection. Semen quality was evaluated by measuring volume, sperm
      concentration, total sperm count (TSC), motility and morphology following WHO
      guidelines. Serum samples were analyzed for reproductive hormones, including
      follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and
      estradiol using immunoassays. Associations between urinary concentrations of
      parabens and semen quality parameters and reproductive hormone levels were
      examined using linear regression, adjusting for potential covariates. Ninety-four
      percent of the men had detectable urinary concentrations of parabens. After
      taking into account important covariates, urinary concentrations of parabens or
      their molar sum were not significantly associated with any semen parameters or
      any of the reproductive hormone levels. Relative to men in the lowest quartile of
      sum of urinary paraben concentrations, the adjusted difference (95% CI) of TSC
      (millions) for men in the 2nd, 3rd, and 4th quartiles were 4.1% (-37.1;45.3), 
      1.6% (-41.9;38.8), and -9.8% (-52.5;32.8), respectively (P-trend=0.55). Our
      results suggest that, in young men, urinary parabens may not adversely impact
      reproductive function, but further research is warranted to confirm these
      findings in other male populations.

PMID- 29179077
TI  - Detection of nanoparticles in Dutch surface waters.
AB  - Nano-enabled consumer products are a likely source of nanoparticles in the
      environment and a number of studies have shown the release of nanoparticles from
      commercial products. Predicted environmental concentrations have been calculated
      but there is a need for real measurement data to validate these calculations.
      However, the detection of engineered nanoparticles in environmental matrices is
      challenging because of the low predicted environmental concentrations which may
      be in the ng/L range. In this study nanosized Ag, CeO2 and TiO2 have been
      measured in multiple surface water samples collected along the rivers Meuse and
      IJssel in the Netherlands using single-particle ICP-MS as measurement technique.
      Validation of the analytical method showed its capability to quantitatively
      determine nanoparticles at low concentrations. Concentration mass detection
      limits for Ag, CeO2 and TiO2 were 0.1ng/L, 0.05ng/L and 10ng/L respectively. Size
      detection limits for Ag, CeO2 and TiO2 were 14, 10 and 100nm. The results of the
      study confirm the presence of nano-sized Ag and CeO2 particles and micro-sized
      TiO2 particles in these surface waters. n-Ag was present in all samples in
      concentrations ranging from 0.3 to 2.5ng/L with an average concentration of
      0.8ng/L and an average particle size of 15nm. n-CeO2 was found in all samples
      with concentrations ranging from 0.4 to 5.2ng/L with an average concentration of
      2.7ng/L and an average particle size of 19nm. Finally, MU-TiO2 was found in all
      samples with a concentration ranging from 0.2 to 8.1MUg/L with an average
      concentration of 3.1MUg/L and an average particle size of 300nm. The particle
      sizes that were found are comparable with the particle sizes that are used in
      nanomaterial applications and consumer products. The nanoparticle concentrations
      confirm the predicted environmental concentrations values in water for all three
      nanoparticles.

PMID- 29179078
TI  - Effects of dam construction and increasing pollutants on the ecohydrological
      evolution of a shallow freshwater lake in the Yangtze floodplain.
AB  - Large river-floodplain systems which provide a variety of societal, economic and
      biological benefits are undergoing extensive and intensive human disturbance.
      However, floodplain lakes responses to multiple stressors are poorly understood.
      The Yangtze River and its floodplain which provide water and food resources for
      more than 300 million people are an important region in China. Hydrological
      regulation as well as socio-economic development have brought profound negative
      influence on this ecologically important area. To improve understanding of
      decadal-scale responses of floodplain lakes to multiple stressors, lake sediment
      proxies including particle size, geochemical elements, diatoms and chironomids
      were analysed in a lead-210 dated core from Futou Lake. The analyses show that
      dams constructed in 1935 and the early 1970s stabilized hydrological conditions
      in Futou Lake and impeded the interaction with the Yangtze River, resulting in a
      decrease in major elements (e.g., Mg, Al, Fe) transported into the lake and an
      increase of macrophyte-related chironomids (C. sylvestris-type, P. penicillatus
      type and Paratanytarsus sp.). After the late 1990s, further decreases in major
      elements and increases in median grain size are attributed to the erosion of the
      Yangtze riverbed and declining supply of major elements-enriched sediments from
      the upper Yangtze caused by the impoundment of the Three Gorges Dam. Chironomid
      and diatom assemblages indicate that hydrological stabilization caused by dam
      constructions stimulated the growth of macrophytes, which may be important in
      buffering against an ecosystem state change towards a phytoplankton-dominated and
      turbid state with ongoing eutrophication. However, a recent increase in Zn, TP
      and the emergence of eutrophic diatom and chironomid species indicate initial
      signs of water quality deterioration which may be related to the combined effects
      of hydrological stabilization and aquaculture. Over all, the sediment record from
      Futou Lake emphasizes the importance of interactions between hydrological change
      and pollutant loads in determining floodplain lake ecosystem state.

PMID- 29179079
TI  - Effects of sea level rise, land subsidence, bathymetric change and typhoon tracks
      on storm flooding in the coastal areas of Shanghai.
AB  - We compared the effects of three key environmental factors of coastal flooding:
      sea level rise (SLR), land subsidence (LS) and bathymetric change (BC) in the
      coastal areas of Shanghai. We use the hydrological simulation model MIKE 21 to
      simulate flood magnitudes under multiple scenarios created from combinations of
      the key environmental factors projected to year 2030 and 2050. Historical
      typhoons (TC9711, TC8114, TC0012, TC0205 and TC1109), which caused extremely high
      surges and considerable losses, were selected as reference tracks to generate
      potential typhoon events that would make landfalls in Shanghai (SHLD), in the
      north of Zhejiang (ZNLD) and moving northwards in the offshore area of Shanghai
      (MNS) under those scenarios. The model results provided assessment of impact of
      single and compound effects of the three factors (SLR, LS and BC) on coastal
      flooding in Shanghai for the next few decades. Model simulation showed that by
      the year 2030, the magnitude of storm flooding will increase due to the
      environmental changes defined by SLR, LS, and BC. Particularly, the compound
      scenario of the three factors will generate coastal floods that are 3.1, 2.7, and
      1.9 times greater than the single factor change scenarios by, respectively, SLR,
      LS, and BC. Even more drastically, in 2050, the compound impact of the three
      factors would be 8.5, 7.5, and 23.4 times of the single factors. It indicates
      that the impact of environmental changes is not simple addition of the effects
      from individual factors, but rather multiple times greater of that when the
      projection time is longer. We also found for short-term scenarios, the bathymetry
      change is the most important factor for the changes in coastal flooding; and for
      long-term scenarios, sea level rise and land subsidence are the major factors
      that coastal flood prevention and management should address.

PMID- 29179080
TI  - Toxicity assessment within the application of in situ contaminated sediment
      remediation technologies: A review.
AB  - Polluted sediment represents a great problem for aquantic environments with
      potential direct acute and chronic effects for the biota and can be tackled with
      both in situ and ex situ treatments. Once dredging activities are not compulsory,
      sediment can be kept in place and managed with techniques involving the use of
      amendment and/or capping. Before their application, the assessment of their
      potential impact to the target environment cannot ignore the safe-by-design
      approach. The role of toxicity in in situ sediment remediation was reviewed
      discussing about how it can be used for the selection of amendments and the
      monitoring of treatment technologies. Results evidenced that capping technology
      coupled to activated carbon (AC) is the most frequently applied approach with
      effects varying according to the rate of contamination in treated sediment, the
      amount of AC used (% v/v), and target biological models considered. Little data
      are available for zerovalent iron as well as other minor amending agents such as
      hematite, natural zeolite, biopolymers and organoclays. Current (eco
      )toxicological information for in situ sediment remediation technologies is
      fragmentary and incomplete or entirely missing, making also the interpretation of
      existing data quite challenging. In situ sediment remediation represents an
      interesting potentially effective approach for polluted sediment recovering. As
      its application in some lab-based and field studies reported to induce negative
      effects for target organisms, amendments and capping agents must be attentively
      evaluated for short- and long-term environmental effects, also in the perspective
      of the remediated site monitoring and maintenance.

PMID- 29179081
TI  - Potential urban runoff impacts and contaminant distributions in shoreline and
      reservoir environments of Lake Havasu, southwestern United States.
AB  - Heavy metal, nutrient, and hydrocarbon levels in and adjacent to Lake Havasu, a
      regionally significant water supply reservoir with a highly controlled, dynamic
      flow regime, are assessed in relation to possible stormwater runoff impacts from
      an arid urban center. Shallow groundwater and sediment analyses from ephemeral
      drainage (wash) mouths that convey stormwater runoff from Lake Havasu City,
      Arizona to the reservoir, provided contaminant control points and correlation
      ties with the reservoir environment. Fine-grain sediments tend to contain higher
      heavy metal concentrations whereas nutrients are more evenly distributed, except
      low total organic carbon levels from young wash mouth surfaces devoid of
      vegetation. Heavy metal and total phosphate sediment concentrations in transects
      from wash mouths into the reservoir have mixed and decreasing trends,
      respectively. Both series may indicate chemical depositional influences from
      urban runoff, yet no statistically significant concentration differences occur
      between specific wash mouths and corresponding offshore transects. Heavy metal
      pollution indices of all sediments indicate no discernible to minor
      contamination, indicating that runoff impacts are minimal. Nevertheless, several
      heavy metal concentrations from mid-reservoir sediment sites increase southward
      through the length of the reservoir. Continual significant water flow through the
      reservoir may help to disperse locally derived runoff particulates, which could
      mix and settle down gradient with chemical loads from upriver sources and local
      atmospheric deposition. Incorporating the shoreline environment with the
      reservoir investigation provides spatial continuity in assessing contaminant
      sources and distribution patterns. This is particularly acute in the
      investigation of energetic, flow-through reservoirs in which sources may be
      overlooked if solely analyzing the reservoir environment.

PMID- 29179082
TI  - Effect of short-term aluminum stress and mycorrhizal inoculation on nitric oxide
      metabolism in Medicago truncatula roots.
AB  - Aluminum (Al) toxicity can induce oxidative and nitrosative stress, which limits
      growth and yield of crop plants. Nevertheless, plant tolerance to stress may be
      improved by symbiotic associations including arbuscular mycorrhiza (AM). Nitric
      oxide (NO) is a signaling molecule involved in physiological processes and plant
      responses to abiotic and biotic stresses. However, almost no information about
      the NO metabolism has been gathered about AM. In the present work, Medicago
      truncatula seedlings were inoculated with Rhizophagus irregularis, and 7-week-old
      plants were treated with 50MUM AlCl3 for 3h. Cytochemical and molecular
      techniques were used to measure the components of the NO metabolism, including NO
      content and localization, expression of genes encoding NO-synthesis (MtNR1, MtNR2
      and MtNIR1) and NO-scavenging (MtGSNOR1, MtGSNOR2, MtHB1 and MtHB2) enzymes and
      the profile of protein tyrosine nitration (NO2-Tyr) in Medicago roots. For the
      first time, NO and NO2-Tyr accumulation was connected with fungal structures
      (arbuscules, vesicles and intercellular hyphae). Expression analysis of genes
      encoding NO-synthesis enzymes indicated that AM symbiosis results in lower
      production of NO in Al-treated roots in comparison to non-mycorrhizal roots.
      Elevated levels of transcription of genes encoding NO-scavenging enzymes
      indicated more active NO scavenging in AMF-inoculated Al-treated roots compared
      to non-inoculated roots. These results were confirmed by less NO accumulation and
      lower protein nitration in Al-stressed mycorrhizal roots in comparison to non
      mycorrhizal roots. This study provides a new insight in NO metabolism in response
      to arbuscular mycorrhiza under normal and metal stress conditions. Our results
      suggest that mycorrhizal fungi decrease NO and tyrosine nitrated proteins content
      in Al-treated Medicago roots, probably via active NO scavenging system.

PMID- 29179083
TI  - Atmospheric CO2 enrichment effect on the Cu-tolerance of the C4 cordgrass
      Spartina densiflora.
AB  - A glasshouse experiment was designed to investigate the effect of the co
      occurrence of 400 and 700ppm CO2 at 0, 15 and 45mM Cu on the Cu-tolerance of C4
      cordgrass species Spartina densiflora, by measuring growth, gas exchange,
      efficiency of PSII, pigments profiles, antioxidative enzyme activities and
      nutritional balance. Our results revealed that the rising atmospheric CO2
      mitigated growth reduction imposed by Cu in plants grown at 45mM Cu, leading to
      leaf Cu concentration bellow than 270mgKg-1 Cu, caused by an evident dilution
      effect. On the other hand, non-CO2 enrichment plants showed leaf Cu concentration
      values up to 737.5mgKg-1 Cu. Furthermore, improved growth was associated with
      higher net photosynthetic rate (AN). The beneficial effect of rising CO2 on
      photosynthetic apparatus seems to be associated with a reduction of stomatal
      limitation imposed by Cu excess, which allowed these plants to maintain greater
      iWUE values. Also, plants grown at 45mM Cu and 700ppm CO2, showed higher ETR
      values and lower energy dissipation, which could be linked with an induction of
      Rubisco carboxylation and supported by the recorded amelioration of N imbalance.
      Furthermore, higher ETR values under CO2 enrichment could lead to an additional
      consumption of reducing equivalents. Idea that was reflected in the lower values
      of ETRmax/AN ratio, malondialdehyde (MDA) and ascorbate peroxidase (APx),
      guaiacol peroxidase (GPx) and superoxide dismutase (SOD) activities under Cu
      excess, which could indicate a lower production of ROS species under elevated CO2
      concentration, due to a better use of absorbed energy.

PMID- 29179084
TI  - Depression, anxiety and PTSD in sexually abused adolescents: Association with
      self-efficacy, coping and family support.
AB  - Sexual abuse has the potential to generate serious emotional consequences for its
      victims, but there is high variability in the symptoms reported by different
      victims. Therefore, it is necessary to ascertain the factors associated with the
      symptoms presented by sexual abuse victims. The aim of the study was to use a
      single model to evaluate the relationship between sexual abuse characteristics
      (frequency, violence, relation with the aggressor and physical commitment),
      cognitive and behavioral factors (self-efficacy, active coping and perceived
      family support) and internalizing symptoms (anxiety, depression and posttraumatic
      stress) in a group of sexually abused adolescents. The participants included 106
      female adolescent victims of sexual abuse (M=14.25years, SD=1.74). The results of
      a path analysis indicated that sexual abuse characteristics were unrelated to
      symptomatology. Only a negative relationship was observed between the victim's
      relationship with the aggressor and PTSD symptomatology. The violence of the
      sexual abuse was negatively related to self-efficacy, and self-efficacy was
      positively related to active coping and negatively related to symptomatology.
      Finally, the perception of family support was positively related to self-efficacy
      and negatively related to symptomatology. These results suggest the need to
      consider the studied factors in the process of psychotherapy with victims of
      sexual abuse.

PMID- 29179085
TI  - Anisotropy (optical, electrical and thermal conductivity) in thin polarizing
      films for UV/Vis regions of spectrum: Experimental and theoretical
      investigations.
AB  - In the present work, the quantum theoretical calculations of the molecular
      structures of the three newly synthesized azomethine dyes: have been predicted
      using Density Functional Theory (DFT) in solvent dimethylformamide (DMF). The
      geometries of the azomethine dyes were optimized using the PBE1PBE/6-31+G level
      of the theory. In addition, the electronic spectra of these compounds in solvent
      DMF were carried out using the TDPBE1PBE, TDPBEPBE, TDB3LYP methods with 6-31G, 6
      31+G, 6-31+G*, 6-31++G* basis sets. After quantum-chemical calculations three new
      azomethine dyes for optoelectronic applications were synthesized. Based on
      polyvinyl alcohol (PVA) and the new synthesized azomethine dyes polarizing films
      for UV/Vis regions of the spectrum were developed. The main optical parameters of
      polarizing PVA-films (Transmittance and Polarization Efficiency) have been
      measured and discussed. Anisotropy of electrical and thermal conductivity of the
      PVA-films has been investigated.

PMID- 29179086
TI  - Xylenes transformation over zeolites ZSM-5 ruled by acidic properties.

PMID- 29179087
TI  - Structural studies on Demospongiae sponges from Gokceada Island in the Northern
      Aegean Sea.
AB  - The Demospongiae is the largest Class in the phylum Porifera (sponges). Most
      sponge species in the Class Demospongiae have a skeleton of siliceous spicules
      and/or protein spongin or both. The first aim of this study was to perform the
      morphological and structural characterization of the siliceous spicules of four
      species belonging to Class Demospongiae (Suberites domuncula, Axinella
      polypoides, Axinella damicornis and Agelas oroides) collected around Gokceada
      Island-Turkey (Northern Aegean Sea). The characterizations were carried out using
      a combination of Scanning Electron Microscopy with Energy Dispersive X-ray
      Spectroscopy (SEM/EDX), Attenuated Total Reflection-Fourier Transform Infrared
      Spectroscopy (ATR-FTIR) and Small Angle X-ray Scattering (SAXS) techniques. The
      sponge Chondrosia reniformis (Porifera, Demospongiae) lacks a structural skeleton
      of spicules or the spongin. It consists mainly of a collagenous tissue. The
      collagen with sponge origin is an important source in biomedical and
      pharmaceutical applications. The second aim of this study was to provide more
      information on the molecular structure of collagen of outer (ectosome) and inner
      (choanosome) regions of the Chondrosia reniformis using ATR-FTIR spectroscopy.
      Hierarchical clustering analysis (HCA) was also used for the discrimination of
      ATR-FTIR spectra of species.

PMID- 29179088
TI  - Reconsideration of the Zincke salt: An efficient colorimetric chemosensor for
      detection of ethylamines.
AB  - In this work, an efficient colorimetric chemosensor for the detection of
      ethylamines using a pyridinium salt (the Zincke salt) is reported. Highly
      sensitive and selective reactivity of the Zincke salt enables colorimetric
      response of the Zincke salt solution to the ethylamines by showing well-defined
      visible color changes from colorless to the deep red. Furthermore, the Zincke
      salt thin film exhibits discernable color changes in response to ethylamine gas
      as well, which allows fabrication of simple, fast and portable strip- and textile
      type ethylamine sensors.

PMID- 29179089
TI  - On the rheology of mixed systems of hydrophobically modified polyacrylate
      microgels and surfactants: Role of the surfactant architecture.
AB  - HYPOTHESIS: The rheological control of suspensions is of key interest in the
      formulation design. A chemically cross-linked hydrophobically modified
      poly(acrylic acid) (HMCL-PAA), used as rheology modifier, is pH sensitive and
      shows swelling behavior above a critical pH due to the ionization of the acrylic
      acid groups. At low pH, HMCL-PAA suspensions are liquid and turbid. The binding
      of surfactants to HMCL-PAA, at low pH conditions, can result in significant
      changes on rheology and transparency of the polymeric suspensions, due to the
      swelling of the microgel particles. EXPERIMENTS: The influence of surfactants
      addition on the rheological properties and transparency of HMCL-PAA suspensions
      was determined. A systematic study was performed using different types of
      surfactants (ionic, non-ionic and zwitterionic). FINDINGS: The gelation
      efficiency of HMCL-PAA suspensions at low pH is strongly dependent on surfactant
      architecture: ionic surfactants are found to be much more efficient than non
      ionic or zwitterionic surfactants. Ionic surfactants lead to a liquid-to-gel
      transition accompanied by an increase of transparency of the suspensions. Among
      the ionic surfactants, anionics show stronger interactions with the polymer. Also
      the surfactant hydrophobicity is relevant; the more hydrophobic the surfactant,
      the stronger is the binding to the polymer and thus the larger the particle
      swelling.

PMID- 29179090
TI  - Versatile hollow fluorescent metal-silica nanohybrids through a modified
      microemulsion synthesis route.
AB  - Silica-metal nanohybrids are common materials for applications in biomedicine,
      catalysis or sensing. Also, hollow structures are of interest as they provide
      additional useful features. However, in these materials the control of the size
      and accessibility to the inner regions of the structure usually requires complex
      synthesis procedures. Here we report a simple colloidal procedure for
      synthesizing hollow silica-metal nanohybrids, driven by the diffusion of metal
      precursors through the porous silica shell and subsequent reduction in aqueous
      solutions. The formation of hollow nanoparticles is controlled by the colloidal
      conditions during synthesis, which affect the ripening of hollow nanoparticles in
      presence of organosilanes. The modification of the conditions during synthesis
      affected the growth of silica precursors in presence of fluorescein
      isothiocyanate (FITC). The limited access to water molecules during the
      hydrolysis of silica precursors is attributed to the hydrophobicity of organic
      fluorescent molecules linked to the condensing silica clusters at the initial
      stages of nanoparticle formation and to the limitation of water content in the
      microemulsion method used. Finally, the growth of metal nanoseeds at the core of
      hollow nanoparticles can be easily achieved though a simple method in aqueous
      environment. The pH and thermal conditions during the reduction process affect
      the formation of metal-silica nanohybrids and their structural features.

PMID- 29179092
TI  - Rheology of particle/water/oil three-phase dispersions: Electrostatic vs.
      capillary bridge forces.
AB  - HYPOTHESIS: Particle/water/oil three-phase capillary suspensions possess the
      remarkable property to solidify upon the addition of minimal amount of the second
      (dispersed) liquid. The hardening of these suspensions is due to capillary
      bridges, which interconnect the particles (pendular state). Electrostatic
      repulsion across the oily phase, where Debye screening by electrolyte is missing,
      could also influence the hardness of these suspensions. EXPERIMENTS: We present
      data for oil-continuous suspensions with aqueous capillary bridges between
      hydrophilic SiO2 particles at particle volume fractions 35-45%. The hardness is
      characterized by the yield stress Y for two different oils: mineral (hexadecane)
      and vegetable (soybean oil). FINDINGS AND MODELLING: The comparison of data for
      the "mirror" systems of water- and oil-continuous capillary suspensions shows
      that Y is lower for the oil-continuous ones. The theoretical model of yield
      stress is upgraded by including a contribution from electrostatic repulsion,
      which partially counterbalances the capillary-bridge attraction and renders the
      suspensions softer. The particle charge density determined from data fits is
      close to that obtained in experiments with monolayers from charged colloid
      particles at oil/water interfaces. The results could contribute for better
      understanding, quantitative prediction and control of the mechanical properties
      of solid/liquid/liquid capillary suspensions.

PMID- 29179091
TI  - Facile approach to synthesize highly fluorescent multicolor emissive carbon dots
      via surface functionalization for cellular imaging.
AB  - Luminescent nanomaterials are encouraging scaffolds for diverse applications such
      as chemical sensors and biosensors, imaging, drug delivery, diagnostics,
      catalysis, energy, photonics, medicine, and so on. Carbon dots (CDs) are a new
      class of luminescent carbonaceous nanomaterial that have appeared recently and
      reaped tremendous scientific interest. Herein, we have exploited a simple
      approach to prepare tuneable and highly fluorescent CDs via surface
      functionalization. The successful synthesis of CDs is manifested from several
      investigations like high-resolution transmission electron microscopy (HRTEM), X
      ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and X-ray
      photoelectron spectroscopy (XPS). The CDs exhibit excellent water solubility and
      with increasing nitrogen content fluorescence quantum yield increases whereas
      cell toxicity decreases. The CD synthesized at high temperature (180  degrees C)
      shows very high quantum yield (more than 56%). The tuneable optical properties of
      CDs are systematically studied using UV-vis and fluorescence spectroscopy. The
      cell viability evaluation and in vitro imaging study reveals that the synthesized
      CDs can be employed as a potential fluorescent probe for bio-imaging without
      further modification.

PMID- 29179093
TI  - Stabilization of spherical nanoparticles of iron(III) hydroxides in aqueous
      solution by wormlike micelles.
AB  - HYPOTHESIS: The low Ksp value of Fe(OH)3 (3 * 10-38 at 298 K) explain the
      immediate coagulation when the pH of a solution of Fe(III) is adjusted to 7.
      However, stable dispersions of Fe(OH)3 can be formed when the pH is adjusted to 7
      in the presence of wormlike micelles formed by cetyltrimethylammonium bromide and
      sodium salicylate. The formation of a structure containing Fe(OH)3 nanoparticles
      decorating wormlike micelles is responsible for the high stability of the
      dispersions. EXPERIMENTS: Fe(OH)3 nanoparticles were obtained by increasing the
      pH of solutions of cetyltrimethylammonium bromide and Fe(III), previously
      complexed with salicylate at pH 3. The interaction between nanoparticles and the
      chains of wormlike micelles was investigated by DLS, SAXS, TEM and Cryo-TEM.
      FINDINGS: DLS revealed higher scattering contrast and slower diffusion for
      wormlike micelles in the presence of nanoparticles. These results were
      interpreted as the decoration of the chains of wormlike micelles by nanoparticles
      of Fe(OH)3. A pearl-necklace model was successfully used to adjust SAXS curves,
      revealing nanoparticles with ~3 nm of diameter, spaced ~2 nm apart along the
      string. This result agrees with TEM and Cryo-TEM images. The formed structure
      prevents the coagulation of nanoparticles, assuring high stability to the
      dispersion.

PMID- 29179094
TI  - Influence of support material on the electrocatalytic activity of nickel oxide
      nanoparticles for urea electro-oxidation reaction.
AB  - Nickel oxide nanoparticles were deposited on different carbon supports including
      activated Vulcan XC-72R carbon black (NiO/AC), multi-walled carbon nanotubes
      (NiO/MWCNTs), graphene (NiO/Gr) and graphite (NiO/Gt) through precipitation step
      followed by calcination at 400  degrees C. To determine the crystalline structure
      and morphology of prepared electrocatalysts, X-ray diffraction (XRD) and
      transmission electron microscopy (TEM) were employed. The electrocatalytic
      activity of NiO/carbon support electrocatalysts was investigated towards urea
      electro-oxidation reaction in NaOH solution using cyclic voltammetry,
      chronoamperometry and electrochemical impedance spectroscopy. Urea oxidation peak
      current density was increased in the following order: NiO/AC < NiO/MWCNTs <
      NiO/Gr < NiO/Gt. Chronoamperometry test also showed an increased steady state
      oxidation current density for NiO/Gt in comparison to other electrocatalysts. The
      increased activity and stability of NiO/Gt electrocatalyst encourage the
      application of graphite as an efficient and cost-saving support to carry metal
      nanoparticles for urea electro-oxidation reaction.

PMID- 29179095
TI  - Pendant capsule elastometry.
AB  - We provide a C/C++ software for the shape analysis of deflated elastic capsules
      in a pendant capsule geometry, which is based on an elastic description of the
      capsule material as a quasi two-dimensional elastic membrane using shell theory.
      Pendant capsule elastometry provides a new in situ and non-contact method for
      interfacial rheology of elastic capsules that goes beyond determination of the
      Gibbs- or dilational modulus from area-dependent measurements of the surface
      tension using pendant drop tensiometry, which can only give a rough estimate of
      the elastic capsule properties as they are based on a purely liquid interface
      model. Given an elastic model of the capsule membrane, pendant capsule
      elastometry determines optimal elastic moduli by fitting numerically generated
      axisymmetric shapes optimally to an experimental image. For each digitized image
      of a deflated capsule elastic moduli can be determined, if another image of its
      undeformed reference shape is provided. Within this paper, we focus on nonlinear
      Hookean elasticity because of its low computational cost and its wide
      applicability, but also discuss and implement alternative constitutive laws. For
      Hookean elasticity, Young's surface modulus (or, alternatively, area compression
      modulus) and Poisson's ratio are determined; for Mooney-Rivlin elasticity, the
      Rivlin modulus and a dimensionless shape parameter are determined; for neo
      Hookean elasticity, only the Rivlin modulus is determined, using a fixed
      dimensionless shape parameter. Comparing results for different models we find
      that nonlinear Hookean elasticity is adequate for most capsules. If series of
      images are available, these moduli can be evaluated as a function of the capsule
      volume to analyze hysteresis or aging effects depending on the deformation
      history or to detect viscoelastic effects for different volume change rates. An
      additional wrinkling wavelength measurement allows the user to determine the
      bending modulus, from which the layer thickness can be derived. We verify the
      method by analyzing several materials, compare the results to available
      rheological measurements, and review several applications. We make the software
      available under the GPL license at github.com/jhegemann/opencapsule.

PMID- 29179096
TI  - Cross-talk between protein synthesis, energy metabolism and autophagy in cancer.
AB  - Translation is a pivotal step in the regulation of gene expression as well as one
      of the most energy consuming processes in the cell. Dysregulation of translation
      caused by the aberrant function of upstream signaling pathways and/or
      perturbations in the expression or function of components of the translation
      machinery is frequent in cancer. In this review, we discuss emerging findings
      that highlight hitherto unappreciated aspects of signaling to the translation
      apparatus with the particular focus on emerging connections between protein
      synthesis, autophagy and energy homeostasis in cancer.

PMID- 29179097
TI  - Preservation of large yellow croaker (Pseudosciaena crocea) by Coagulin L1208, a
      novel bacteriocin produced by Bacillus coagulans L1208.
AB  - Large yellow croaker (Pseudosciaena crocea) is a cultivated fish of great
      economic importance and abundant nutritional value. However, due to its high
      protein and water contents, it is susceptible to decomposition, leading to
      considerable economic loss and adverse effects on consumer health. Here, we
      assessed the function of the bacterial strain Bacillus coagulans L1208 (Bcoa) in
      preserving large yellow croaker during storage at 4 degrees C and found that Bcoa
      elongates the shelf-life significantly. Further investigations showed that Bcoa
      prolongs the storage time mainly by suppressing the growth of spoilage bacteria.
      Moreover, a novel bacteriocin, designated as Coagulin L1208 and produced by Bcoa,
      was purified and identified by N-terminal sequencing. Finally, the activity of
      Coagulin L1208 for suppressing spoilage bacteria during the preservation of large
      yellow croaker was assessed. Our results reveal the mechanism by which Bcoa aids
      the preservation of large yellow croaker and identify Coagulin L1208 as a
      potential novel antiseptic.

PMID- 29179098
TI  - The antibacterial activity of clove oil/chitosan nanoparticles embedded gelatin
      nanofibers against Escherichia coli O157:H7 biofilms on cucumber.
AB  - This study aims to evaluate the antibacterial activity of clove oil-loaded
      chitosan nanoparticles (CO@CNPs) and gelatin electrospun nanofibers against
      Escherichia coli O157:H7 (E. coli O157:H7) biofilms on cucumbers. The optimal
      CO@CNPs were prepared when the initial concentration of clove oil (CO) was
      2.5mg/mL according to the ionic crosslinking method. CO@CNPs showed high
      antibacterial activity against E. coli O157:H7 biofilms. After 8h treatment,
      almost 99.98% reduction in E. coli O157:H7 population was achieved when CO@CNPs
      were applied at 30% (w/v). Subsequently, the prepared CO@CNPs were incorporated
      successfully within gelatin nanofibers by electrospinning. After 9mg/mL
      gelatin/CO@CNPs treatment for 24h, the population of E. coli O157:H7 biofilm
      reduced by about 99.99% in vitro. Further, the application of gelatin/CO@CNPs
      nanofibers on cucumber against E. coli O157:H7 biofilm was evaluated as well.
      After 6mg/mL and 9mg/mL gelatin/CO@CNPs nanofibers treatment at 12 degrees C for
      4days, 4.28 and 4.97 log10 reductions of E. coli O157:H7 biofilm in population
      were observed, respectively. Finally, the sensory evaluation results implied that
      the gelatin/CO@CNPs nanofibers treatment could maintain the color and flavor of
      cucumber well for >4days.

PMID- 29179099
TI  - Influence of fermentation and other processing steps on the folate content of a
      traditional African cereal-based fermented food.
AB  - Folate deficiency can cause a number of diseases including neural tube defects
      and megaloblastic anemia, and still occurs in both developed and developing
      countries. Cereal-based food products are staple foods in many countries, and may
      therefore be useful sources of folate. The production of folate by microorganisms
      has been demonstrated in some cereal-based fermented foods, but has never been
      studied in a traditional African cereal based food spontaneously fermented. The
      microbiota of ben-saalga, a pearl-millet based fermented porridge frequently
      consumed in Burkina Faso, has a good genetic potential for the synthesis of
      folate, but the folate content of ben-saalga is rather low, suggesting that
      folate is lost during the different processing steps. The aim of this study was
      therefore to monitor changes in folate content during the different steps of
      preparing ben-saalga, from pearl-millet grains to porridge. Traditional
      processing involves seven different steps: washing, soaking, grinding, kneading,
      sieving, (spontaneous) fermentation, and cooking. Two type of porridge were
      prepared, one using a process adapted from the traditional process, the other a
      modified process based on fermentation by backslopping. Dry matter and total
      folate contents were measured at each step, and a mass balance assessment was
      performed to follow folate losses and gains. Folate production was observed
      during the soaking of pearl-millet grains (+26% to +79%), but the folate content
      of sieved batters (2.5 to 3.4MUg/100g fresh weight) was drastically lower than
      that of milled soaked grains (17.3 to 19.4MUg/100g FW). The final folate content
      of the porridges was very low (1.5 to 2.4MUg/100g FW). The fermentation had no
      significant impact on folate content, whatever the duration and the process used.
      This study led to a better understanding of the impact on folate of the different
      processing steps involved in the preparation of ben-saalga.

PMID- 29179100
TI  - Middle-up analysis of monoclonal antibodies after combined IgdE and IdeS hinge
      proteolysis: Investigation of free sulfhydryls.
AB  - Despite significant analytical improvements during this last decade,
      characterizing the whole integrity of monoclonal antibodies during their
      bioproduction remains a challenge. In this study, we report a new analytical
      approach to evaluate the overall heterogeneity/integrity of mAbs by LC-MS after
      combined proteolysis at their lower- and upper-hinge sites using the
      immunoglobulin-degrading enzymes IdeS and IgdE respectively. The whole sample
      preparation did not use any harsh conditions such as low pH, high temperature or
      reductive conditions and enables the splitting of mAbs structure into three
      fragments, namely the hinge dimer, Fab and Fc/2. Using the NIST mAb reference
      material, this method was demonstrated to be particularly suited for the analysis
      of mAbs disulfide bridges. The three fragments as well as their corresponding
      free sulfhydryl forms were well separated by chromatography and identified online
      by mass spectrometry. The method was then successfully applied to several mAbs of
      variable hydrophobicities.

PMID- 29179101
TI  - The "Cinderella Syndrome": A narrative study of social curfews and lifestyle
      restrictions in juvenile myoclonic epilepsy.
AB  - Several factors are thought to contribute to inadequate seizure control in
      patients with juvenile myoclonic epilepsy (JME), including drug resistance,
      neuropsychiatric comorbidity, and poor lifestyle choices. Recent evidence
      supports the existence of frontal lobe microstructural deficits and behavioral
      changes that may contribute to poor seizure control in a minority of patients.
      Counseling patients on the importance of adequate sleep hygiene and alcohol
      restriction is an important part of the management strategy for patients with
      JME. However, information is lacking on how these lifestyle restrictions impact
      on patients with JME. We conducted a qualitative descriptive analysis of the
      social impact of JME on 12 patients, from their own perspective. We identified
      four prominent themes: the importance of alcohol use as a social "norm", how JME
      affected relationships, decision making (risk versus consequences), and knowledge
      imparting control. Given that these restrictions were interpreted by patients as
      social "curfews", we suggest that the term "Cinderella Syndrome" encapsulates the
      perceived imperative to be home before midnight. Our findings underscore the
      importance for clinicians to recognize that in counseling patients with JME about
      lifestyle adjustments, there may be a significant social consequence unique to
      this patient group.

PMID- 29179102
TI  - Electroencephalographic findings in anti-N-methyl-d-aspartate receptor
      encephalitis in children: A series of 12 patients.
AB  - OBJECTIVE: Anti-N-methyl-d-aspartate receptor encephalitis (a-NMDARe) is an acute
      or subacute encephalopathy where electroencephalogram (EEG) is frequently
      obtained as part of the workup. Although no diagnostic EEG finding has been
      described so far, the definition of specific or typical patterns might help to
      distinguish this group among various encephalopathies of childhood. We examined
      EEG recordings of our patients with a-NMDARe in order to describe the most
      frequent findings. METHODS: Clinical and laboratory data and digital EEG
      recordings of 12 pediatric patients diagnosed with a-NMDARe in two major child
      neurology centers are evaluated. RESULTS: We reviewed 43 EEG recordings from 12
      children with a-NMDARe and followed their evolution for a median of 6 (range: 1
      60) months. Initial EEG was abnormal in 11/12 patients. The most frequent finding
      was focal or diffuse slowing of the background rhythm. Generalized rhythmic delta
      activity, brief rhythmic discharges (BRDs), and occipital intermittent rhythmic
      delta activity (OIRDA) were seen in two patients each. Diffuse excess beta
      frequency activity was seen in three patients. Extreme delta brushes were
      observed in 5/12 (41.7%) patients, disappeared in 4-6months (two patients), or
      persisted at 10-17months (two patients). Epileptic activity was seen in seven
      patients (58%) and lateralized periodic discharges in one. On follow-up EEGs,
      most epileptic activity disappeared in a median of 8months. CONCLUSIONS: A normal
      EEG is rare in a-NMDARe. Focal or diffuse slowing, epileptic activity, and
      extreme delta brush are common findings. Epileptic activity in early EEGs do not
      persists in most patients. Severe diffuse slowing may predict neurological
      impairment if confirmed in larger series.

PMID- 29179103
TI  - Factors associated with behavioral problems and cognitive impairment in children
      with epilepsy of Kinshasa, Democratic Republic of the Congo.
AB  - BACKGROUND: Behavioral problems and cognitive impairment are common in children
      with epilepsy (CWE). In sub-Saharan Africa, little is known about these
      comorbidities particularly their relationships with socioeconomic features. The
      goal of this study was to identify clinical and socioeconomic factors associated
      with behavioral problems and cognitive impairment in CWE of Kinshasa (Democratic
      Republic of the Congo). METHODS: This cross-sectional hospital-based study had
      included 104 CWE aged 6 to 17years. Behavioral problems were assessed by the
      child behavior checklist. The Wechsler nonverbal scale of ability was used to
      assess cognitive impairment. RESULTS: At least one behavioral problem was found
      in 34.6% of CWE. Internalized problems were increasing with father's age
      (p=0.034). Externalized problems were increasing with the decreased of mother's
      age (p=0.009) and with a previous antiepileptic treatment (p=0.032). Total
      behavioral problems were increasing with a previous antiepileptic treatment
      (p=0.029). Cognitive impairment was present in 73.3% of CWE. It was more common
      in boys (p=0.013), and it was increasing with a low household daily expenses
      (p=0.034), with a previous antiepileptic treatment (p=0.041), with an early onset
      of epileptic seizures (p=0.042), and with a high frequency of epileptic seizures
      (p=0.011). CONCLUSION: Behavioral problems and cognitive impairment are common in
      CWE. Multivariate analysis has shown that behavioral problems were associated
      with socioeconomic features only. Contrariwise, cognitive impairment was
      associated with both socioeconomic factors and clinical features. There is a need
      of more studies to improve knowledge of these comorbidities in the sub-Saharan
      Africa context.

PMID- 29179104
TI  - Who are the individuals diagnosed with epilepsy using the Public Health System in
      the city of Pelotas, southern Brazil?
AB  - The aim of this study was to describe sociodemographic, clinical, behavioral,
      nutritional, and health-related variables from people with epilepsy. A
      descriptive observational study was carried out in the city of Pelotas, southern
      Brazil. Sociodemographic, clinical, behavioral, nutritional, and health-related
      variables were collected. A univariate analysis was performed, calculating the
      measures of central tendency for continuous variables and proportions for
      categorical ones. The sample consisted of 101 people, age ranging from 12 to
      75years, mostly male (50.5%) and white (59.4%). Only 37.2% from the sample was
      employed, and the average income was R$ 788.00 Brazilian Reais (US$ 245.90 at the
      moment of the interview). From all the subjects, 65.6% was in treatment with
      monotherapy, 62.9% presented more than 15 seizures during the life, 67.3% showed
      active epilepsy, 64.6% were physically inactive, 52.5% presented normal body mass
      index, and 50% showed generalized seizures. The most used antiepileptic drug was
      the carbamazepine. The average score of depression was 12.6+/-4.1 points and
      34.6% showed severe depressive symptoms (equal or higher than 15 points). The
      mean score of trait and state anxiety was 12.2+/-3.6 and 15.1+/-3.4 points,
      respectively (ranging from 6 to 24 points). The mean score of quality of life and
      stress was 63.2+/-18.2 (ranging from 0 to 100 points) and 21.2+/-7.1 points
      (ranging from 0 to 40 points), respectively. Considering the medication side
      effects, the mean score was 42.4+/-8.9 points, 38.5% showing high rates (higher
      than 45 points), and only 16% showing good sleep quality. In conclusion, these
      results are important to improve understanding of these individuals' disease and
      to subsidize the specific public policies in countries of low and middle income.

PMID- 29179105
TI  - Predicting epileptic seizure control during pregnancy.
AB  - OBJECTIVE: The objective of the study was to assess whether the type of seizure
      disorder present in the prospective mother with epilepsy, her use of
      antiepileptic drugs (AEDs) in early pregnancy, and her seizure control before
      pregnancy help predict her prospects for seizure freedom throughout pregnancy.
      METHODS: This paper is based on data accumulated in the Australian Pregnancy
      Register (APR) between 1998 and late 2016. Information was analyzed concerning
      epileptic seizure occurrence and AED therapy taken before and during pregnancy,
      using simple statistical and confidence interval (C.I.) methods, mainly relative
      risk (R.R.) calculations. RESULTS: After excluding pregnancies lost to follow-up,
      and those that ended prematurely because of spontaneous abortion or stillbirth,
      1939 pregnancies were available for study. Seizures had occurred during pregnancy
      in 829 (42.8%), and convulsive seizures in 385 (19.9%). Seizures of any type
      occurred in 78.4% of pregnancies where seizures had occurred in the previous year
      (active epilepsy) and in 22.3% of those associated with inactive epilepsy.
      Seizures of any type had occurred in 54.9% of pregnancies initially unexposed to
      AEDs and in 45.5% of those treated with AEDs throughout. The corresponding
      figures for convulsive seizures during pregnancy were 31.7% and 22.3%. There was
      statistically significant evidence that, in women with epilepsy (WWE), having a
      seizure disorder that was active in the prepregnancy year and one untreated in
      early pregnancy was associated with decreased prospects of seizure freedom during
      pregnancy. Decreased chances of seizure-free pregnancies in women with focal
      epilepsies and those treated with multiple AEDs were probably explained by
      greater frequencies of active seizure disorders in these patient categories.
      CONCLUSIONS: Women with epilepsy who experience seizures in the year prior to
      pregnancy appear 3 or 4 times more likely to continue to have seizures during
      pregnancy than women whose seizures are fully controlled prior to pregnancy. Not
      taking AEDs in early pregnancy also increases the hazard for seizure occurrence
      in pregnancy.

PMID- 29179106
TI  - Quality of life in adults with epilepsy is associated with anticonvulsant
      polypharmacy independent of seizure status.
AB  - RATIONALE: Polypharmacy, sometimes necessary to control epilepsy, can result in
      adverse effects that may affect quality of life (QOL). Our purpose was to
      determine the association of polypharmacy with QOL. METHODS: Two hundred seven
      patients with epilepsy were surveyed on characteristics within the last 4weeks:
      QOL Quality of Life in Epilepsy-Patient-Weighted (QOLIE-10-P) and seizure status
      (seizure-free or not), demographics, epilepsy characteristics, insomnia,
      sleepiness, mood, sleep-wake timing, healthcare use, and employment. Those on
      polypharmacy (antiepileptic drug (AED)>1) were compared with controls (AED=1)
      with univariate comparisons and subsequent multivariate regression. RESULTS:
      Patients on polypharmacy had worse QOL scores (mean 33.3+/-6.9 versus 36.7+/
      5.7), were less likely to be seizure-free (39 (44%) versus 82 (68%)), had more
      evening-weighted wakefulness, and were more likely unemployed (74% versus 49%).
      Polypharmacy was associated with worse QOL (odds ratio 1.068 and 95th CI 1.018
      1.121) even after controlling for seizure status. Covariates offered no
      improvement to the model. CONCLUSION: Polypharmacy was associated with worse QOL
      in patients with epilepsy despite seizure control. Further investigation into
      specific etiology of polypharmacy's influence on QOL is warranted in order to
      develop paradigms for optimal treatment.

PMID- 29179107
TI  - Local redox environment beneath biological membranes probed by palmitoylated
      roGFP.
AB  - Production of reactive oxygen species (ROS) and consequent glutathione oxidation
      are associated with various physiological processes and diseases, including cell
      differentiation, senescence, and inflammation. GFP-based redox sensors provide a
      straight-forward approach to monitor ROS levels and glutathione oxidation within
      a living cell at the subcellular resolution. We utilized palmitoylated versions
      of cytosolic glutathione and hydrogen peroxide sensors (Grx1-roGFP2 and roGFP2
      Orp1, respectively) and demonstrated a unique redox environment near biological
      membranes. In HeLa cells, cytosolic glutathione was practically completely
      reduced (EGSH/GSSG = - 333mV) and hydrogen peroxide level was under the
      detectable range. In contrast, the cytoplasmic milieu near membranes of
      intracellular vesicles exhibited significant glutathione oxidation (EGSH/GSSG > -
      256mV) and relatively high H2O2 production, which was not observed for the plasma
      membrane. These vesicles colocalized with internalized EGFR, suggesting that H2O2
      production and glutathione oxidation are characteristics of cytoplasmic surfaces
      of the endocytosed vesicles. The results visually illustrate local redox
      heterogeneity within the cytosol for the first time.

PMID- 29179109
TI  - Bacterial nitrogen fixation in sand bioreactors treating winery wastewater with a
      high carbon to nitrogen ratio.
AB  - Heterotrophic bacteria proliferate in organic-rich environments and systems
      containing sufficient essential nutrients. Nitrogen, phosphorus and potassium are
      the nutrients required in the highest concentrations. The ratio of carbon to
      nitrogen is an important consideration for wastewater bioremediation because
      insufficient nitrogen may result in decreased treatment efficiency. It has been
      shown that during the treatment of effluent from the pulp and paper industry,
      bacterial nitrogen fixation can supplement the nitrogen requirements of suspended
      growth systems. This study was conducted using physicochemical analyses and
      culture-dependent and -independent techniques to ascertain whether nitrogen
      fixing bacteria were selected in biological sand filters used to treat synthetic
      winery wastewater with a high carbon to nitrogen ratio (193:1). The systems
      performed well, with the influent COD of 1351 mg/L being reduced by 84-89%. It
      was shown that the nitrogen fixing bacterial population was influenced by the
      presence of synthetic winery effluent in the surface layers of the biological
      sand filters, but not in the deeper layers. It was hypothesised that this was due
      to the greater availability of atmospheric nitrogen at the surface. The numbers
      of culture-able nitrogen-fixing bacteria, including presumptive Azotobacter spp.
      exhibited 1-2 log increases at the surface. The results of this study confirm
      that nitrogen fixation is an important mechanism to be considered during
      treatment of high carbon to nitrogen wastewater. If biological treatment systems
      can be operated to stimulate this phenomenon, it may obviate the need for
      nitrogen addition.

PMID- 29179110
TI  - LAND-deFeND - An innovative database structure for landslides and floods and
      their consequences.
AB  - Information on historical landslides and floods - collectively called "geo
      hydrological hazards - is key to understand the complex dynamics of the events,
      to estimate the temporal and spatial frequency of damaging events, and to
      quantify their impact. A number of databases on geo-hydrological hazards and
      their consequences have been developed worldwide at different geographical and
      temporal scales. Of the few available database structures that can handle
      information on both landslides and floods some are outdated and others were not
      designed to store, organize, and manage information on single phenomena or on the
      type and monetary value of the damages and the remediation actions. Here, we
      present the LANDslides and Floods National Database (LAND-deFeND), a new database
      structure able to store, organize, and manage in a single digital structure
      spatial information collected from various sources with different accuracy. In
      designing LAND-deFeND, we defined four groups of entities, namely: nature
      related, human-related, geospatial-related, and information-source-related
      entities that collectively can describe fully the geo-hydrological hazards and
      their consequences. In LAND-deFeND, the main entities are the nature-related
      entities, encompassing: (i) the "phenomenon", a single landslide or local
      inundation, (ii) the "event", which represent the ensemble of the inundations
      and/or landslides occurred in a conventional geographical area in a limited
      period, and (iii) the "trigger", which is the meteo-climatic or seismic cause
      (trigger) of the geo-hydrological hazards. LAND-deFeND maintains the relations
      between the nature-related entities and the human-related entities even where the
      information is missing partially. The physical model of the LAND-deFeND contains
      32 tables, including nine input tables, 21 dictionary tables, and two association
      tables, and ten views, including specific views that make the database structure
      compliant with the EC INSPIRE and the Floods Directives. The LAND-deFeND database
      structure is open, and freely available from
      http://geomorphology.irpi.cnr.it/tools.

PMID- 29179108
TI  - A hypermorphic antioxidant response element is associated with increased MS4A6A
      expression and Alzheimer's disease.
AB  - Late onset Alzheimer's disease (AD) is a multifactorial disorder, with AD risk
      influenced by both environmental and genetic factors. Recent genome-wide
      association studies (GWAS) have identified genetic loci associated with increased
      risk of developing AD. The MS4A (membrane-spanning 4-domains subfamily A) gene
      cluster is one of the most significant loci associated with AD risk, and MS4A6A
      expression is correlated with AD pathology. We identified a single nucleotide
      polymorphism, rs667897, at the MS4A locus that creates an antioxidant response
      element and links MS4A6A expression to the stress responsive Cap-n-Collar (CNC)
      transcription factors NRF1 (encoded by NFE2L1) and NRF2 (encoded by NFE2L2). The
      risk allele of rs667897 generates a strong CNC binding sequence that is activated
      by proteostatic stress in an NRF1-dependent manner, and is associated with
      increased expression of the gene MS4A6A. Together, these findings suggest that
      the cytoprotective CNC regulatory network aberrantly activates MS4A6A expression
      and increases AD risk in a subset of the population.

PMID- 29179111
TI  - Investigation of the interaction between the fate of antibiotics in aquafarms and
      their level in the environment.
AB  - China is the largest freshwater aquaculture producer and antibiotics consumer in
      the world, and rivers in China are generally polluted by antibiotics. However,
      there is little information available regarding the linkage of antibiotics in
      aquaculture and the aquatic environment. Therefore, this study investigated the
      fate of antibiotics in several open water culture-based freshwater aquafarms,
      including integrated livestock/fish systems and non-integrated fish ponds, and
      explored the contamination profiles of antibiotics in the Beijiang River. Then
      the study tried to clarify the two-way interaction of antibiotics in aquaculture
      and the environment. The results showed that, when compared with the effluent
      from livestock farms and wastewater treatment plants, the contribution of
      antibiotics from non-integrated fish pond water without livestock sewage input
      was limited, while that of effluent from the integrated livestock/fish system was
      quite high. The total concentrations of antibiotics detected in the aquafarm
      source water were similar to those in the upper river water and generally higher
      than those in the corresponding fish pond water, implying that the occurrence of
      antibiotics in intensive aquafarms can mainly be attributed to the antibiotic
      residues in nearby river water. Overall, the results underscore the need to
      develop a sewage infrastructure for the treatment of effluent from integrated
      livestock/fish aquafarms, and suggest that open water culture-based fish farms
      should be located far from seriously contaminated sections of rivers.

PMID- 29179112
TI  - Participatory assessment of soil erosion severity and performance of mitigation
      measures using stakeholder workshops in Koga catchment, Ethiopia.
AB  - Farmers possess a wealth of knowledge regarding soil erosion and soil and water
      conservation (SWC), and there is a great demand to access it. However, there has
      been little effort to systematically document farmers' experiences and
      perceptions of SWC measures. Sustainable Land Management (SLM) has largely
      evolved through local traditional practices rather than adoption based on
      scientific evidence. This research aimed to assess soil erosion and performance
      of different SWC measures from the farmers' perspective by documenting their
      perceptions and experiences in Koga catchment, Ethiopia. To this aim, workshops
      were organised in three sub-catchments differing in slopes and SWC measures.
      Workshops included group discussions and field monitoring of erosion indicators
      and systematically describing the status of soil erosion, soil fertility and
      yield to assess the performance of SWC measures. Results show that farmers are
      aware of the harmful effects of ongoing soil erosion and of the impacts of
      mitigation measures on their farms. Sheet erosion was found to be the most
      widespread form of erosion while rill damage was critical on plots cultivated to
      cereals on steep slopes. The average rill erosion rates were 24.2 and 47.3 t/ha/y
      in treated and untreated farmlands, respectively. SWC reduced rill erosion on
      average by more than 48%. However, the impacts of SWC measures varied
      significantly between sub-watersheds, and farmers believed that SWC measures did
      not prevent erosion completely. Comparatively, graded stone-faced soil bunds
      revealed maximum desired impacts and were most appreciated by farmers, whereas
      level bunds caused water logging. Most traditional ditches were highly graded and
      begun incising and affected production of cereals. Despite the semi-quantitative
      nature of the methodology, using farmers' perceptions and experiences to document
      land degradation and the impacts of SWC measures is crucial as they are the daily
      users of the land and therefore directly affecting the success or failure of SWC
      measures.

PMID- 29179113
TI  - Effects of pH dynamics on solidification/stabilization of municipal solid waste
      incineration fly ash.
AB  - Fly ash (FA), a product of municipal solid waste incineration (MSWI), has been
      classified as a kind of hazardous waste due to its high content of heavy metals.
      FA may be reused in the construction industry or disposed of at landfill sites,
      and thus poses threats to both the environment and human health. This study
      sought to establish a scientific basis for accurate selection of suitable pH
      storage conditions for the FA. We evaluated the potential of MSWI FA sample from
      the Xinghuo waste incineration power plant, Wuhan, to solidify/stabilize the
      heavy metal (Cu, Pb, Zn, Cr, Cd, As and Mn) contents, when leached under
      different pH conditions. The concentration of a heavy metal in the leachate was
      assumed to inversely reflect the extent of its solidification/stabilization
      (S/S). The study findings showed that the raw FA contained higher levels of the
      heavy metals, which were above the acceptable limits. Extremely acidic conditions
      favoured heavy metal leaching compared to extremely alkaline conditions. The
      extent of S/S of heavy metals was generally very low under highly acidic
      conditions (pH <= 4), but increased with increasing pH. All the metals
      solidified/stabilized in pH media of 5-11, except Zn which was detected in the
      entire pH range. We conclude that changing landfill conditions which can affect
      the pH environment, will increase heavy metal leaching when the pH <= 4. As a
      result, waste which was initially classified as non-hazardous may later pose
      harmful risks to both humans and the environment alike. We propose pH of 5-11 as
      the optimum pH range for the treatment, reuse, and disposal of the ash sample.

PMID- 29179114
TI  - Valorization of Poly (ethylene) terephthalate (PET) wastes into magnetic carbon
      for adsorption of antibiotic from water: Characterization and application.
AB  - Waste Polyethylene terephthalate (PET) bottles were pyrolyzed in the presence of
      nitrogen and converted into activated carbon (PETAC) by physical activation in
      carbon dioxide flow. An ex-situ precipitation and external reduction method were
      applied for the intercalation of ferromagnetic iron oxides onto the PETAC matrix.
      The characteristic structural and chemical properties of PETAC and magnetic PETAC
      (M-PETAC) were studied by Brunauer Emmett Teller (BET) surface area analysis,
      Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM),
      Fourier Transform Infrared (FTIR) analysis, Raman spectroscopy, X-Ray Diffraction
      (XRD) analysis, Energy Dispersive analysis of X-rays (EDAX), Vibrating Sample
      Magnetometer (VSM), Thermal gravimetric analysis (TGA) and elemental analysis.
      Characterization results indicated that PETAC exhibited a relatively smooth and
      microporous texture with a surface area of 659.6 m2g-1 while M-PETAC displayed a
      rugged morphology with a diminished surface area of 288.8 m2g-1. XRD measurements
      confirmed the formation of iron oxide nanocrystallites with an average Scherrer
      crystallite size of 19.2 nm. M-PETAC delivered a quick response to an external
      magnet and exhibited saturation magnetization value of 35.4 emu g-1. PETAC and M
      PETAC were explored as potential adsorbents for the adsorption of a
      pharmaceutical (cephalexin) from water. Isotherm analysis revealed that M-PETAC
      exhibited a superior adsorption capacity (71.42 mg g-1) compared to PETAC (21.27
      mg g-1). FTIR analysis of the adsorbents after CEX adsorption revealed the role
      of FeO as the nucleation site for enhanced adsorption of cephalexin by M-PETAC.

PMID- 29179115
TI  - An evaluative tool for rapid assessment of derelict vessel effects on coastal
      resources.
AB  - Derelict vessels impact coastal and estuarine habitats, fisheries resources, are
      aesthetically unappealing, and may be a hazard to navigation and recreation. The
      Government Accountability Office estimated in 2013 over 5600 derelict vessels
      existed throughout the coastal United States. Considering the large number of
      derelict vessels present in coastal areas, effective tools are needed to assess
      the environmental damage exerted by derelict vessels and aid in management
      strategies for their removal. After carefully reviewing regulations, we developed
      a 100-point scoring rubric (DVET) to evaluate damage by derelict vessels to
      natural resources with minimal field effort. The DVET's ability to rapidly assess
      a derelict vessel's impact on surrounding natural resources was confirmed with
      additional rigorous sampling and suggest environmental enhancement following
      vessel removal. The DVET shows promise for informing derelict vessel removal
      strategies, although more work is needed to quantify environmental benefits of
      derelict vessel removal and establish guidelines for removal prioritization.

PMID- 29179116
TI  - Evaluation of fly ash pellets for phosphorus removal in a laboratory scale
      denitrifying bioreactor.
AB  - Nitrate and orthophosphate from agricultural activities contribute significantly
      to nutrient loading in surface water bodies around the world. This study
      evaluated the efficacy of woodchips and fly ash pellets in tandem to remove
      nitrate and orthophosphate from simulated agricultural runoff in flow-through
      tests. The fly ash pellets had previously been developed specifically for
      orthophosphate removal for this type of application, and the sorption bench
      testing showed a good promise for flow-through testing. The lab-scale horizontal
      flow bioreactor used in this study consisted of an upstream column filled with
      woodchips followed by a downstream column filled with fly ash pellets (3 and 1 m
      lengths, respectively; both 0.15 m diameter). Using influent concentrations of 12
      mg/L nitrate and 5 mg/L orthophosphate, the woodchip bioreactor section was able
      to remove 49-85% of the nitrate concentration at three hydraulic retention times
      ranging from 0.67 to 4.0 h. The nitrate removal rate for woodchips ranged from 40
      to 49 g N/m3/d. Higher hydraulic retention times (i.e., smaller flow rates)
      corresponded with greater nitrate load reduction. The fly ash pellets showed
      relatively stable removal efficiency of 68-75% across all retention times. Total
      orthophosphate adsorption by the pellets was 0.059-0.114 mg P/g which was far
      less than the saturated capacity (1.69 mg/g; based on previous work). The fly ash
      pellets also removed some nitrate and the woodchips also removed some
      orthophosphate, but these reductions were not significant. Overall, woodchip
      denitrification followed by fly ash pellet P-sorption can be an effective
      treatment technology for nitrate and phosphate removal in subsurface drainage.

PMID- 29179117
TI  - Investigation of kinetics and absorption isotherm models for hydroponic
      phytoremediation of waters contaminated with sulfate.
AB  - Two common wetland plants, Pampas Grass (Cortaderia selloana) and Lucky Bamboo
      (Dracaena sanderiana), were used in hydroponic cultivation systems for the
      treatment of simulated high-sulfate wastewaters. Plants in initial experiments at
      pH 7.0 removed sulfate more efficiently compared to the same experimental
      conditions at pH 6.0. Results at sulfate concentrations of 50, 200, 300, 600,
      900, 1200, 1500 and 3000 mg/L during three consecutive 7-day treatment periods
      with 1-day rest intervals, showed decreasing trends of both removal efficiencies
      and uptake rates with increasing sulfate concentrations from the first to the
      second to the third 7-day treatment periods. Removed sulfate masses per unit dry
      plant mass, calculated after 23 days, showed highest removal capacity at 600 mg/L
      sulfate for both plants. A Langmuir-type isotherm best described sulfate uptake
      capacity of both plants. Kinetic studies showed that compared to pseudo first
      order kinetics, pseudo-second order kinetic models slightly better described
      sulfate uptake rates by both plants. The Elovich kinetic model showed faster
      rates of attaining equilibrium at low sulfate concentrations for both plants. The
      dimensionless Elovich model showed that about 80% of sulfate uptake occurred
      during the first four days' contact time. Application of three 4-day contact
      times with 2-day rest intervals at high sulfate concentrations resulted in
      slightly higher uptakes compared to three 7-day contact times with 1-day rest
      intervals, indicating that pilot-plant scale treatment systems could be sized
      with shorter contact times and longer rest-intervals.

PMID- 29179118
TI  - Performance improvement of a thermophilic sulfate-reducing bioreactor under
      acidogenic conditions: Effects of diversified operating strategies.
AB  - The establishment of a sulfidogenic environment under thermophilic (55  degrees
      C) acidogenic conditions was assessed in an innovative structured-bed bioreactor
      to enhance sulfate removal and acetate production prior to methanogenesis.
      Diversified operating strategies, i.e., variations in the hydraulic retention
      time (HRT; 6-12 h), sulfate loading rate (SLR; 8-16 kg SO42- m-3 day-1) and
      liquid phase recirculation ratio (0.0-57.0) were assessed to both enable the
      establishment of sulfate-reducing conditions and remove H2S from the liquid
      phase. Ethanol was used as the only carbon source. Applying a low HRT (6 h) as
      the initial operating strategy severely hindered the establishment of sulfate
      reducing bacteria (SRB) populations within the system (sulfate removal < 27.5%).
      In turn, applying effluent recirculation had a positive impact on the system
      (sulfate removal ~ 60%) by providing an adequate buffer control along the entire
      height of the system, as well by displacing over 70% of the H2S to the gaseous
      phase. The maintenance of pH values above 6.1 proved to be adequate for the
      sulfidogenic activity, whereas enhanced acidic conditions (pH < 6.0) at the basal
      portion of the reactor comprised a determining factor to hinder sulfate
      reduction. SRB were able to handle H2S and acetate concentrations as high as 232
      mg L-1 and 3111 mg L-1, respectively, after establishing an effective
      acidogenic/sulfidogenic environment, indicating that the proposed system has the
      potential to be used as the first stage in the anaerobic processing of sulfate
      rich wastewater streams.

PMID- 29179119
TI  - Planning support tools and their effects in participatory urban adaptation
      workshops.
AB  - In the face of a changing climate, many cities are engaged in adaptation planning
      and are using participatory workshops to involve stakeholders in these
      initiatives. Different tools are being used to structure the process and content
      of participatory planning workshops, but it is unclear what effect the tools have
      on the workshops and their results. We evaluated three different tools (Group
      Model Building, the Adaptation Support Tool, and the Stress Test Guideline) and a
      tool-free approach in repeated simulated workshops, to observe and compare (1)
      the way workshops played out, and (2) the direct outcomes that were achieved.
      Tools appear to influence both aspects. Specifically, we measured differences in
      the learning effects in groups, in the development of shared understanding within
      groups, in the types of plans that are developed by groups, and in the nature of
      participation during the workshops. Further research is needed to translate these
      results into practice, but this is a first step in advancing knowledge about the
      influence of tools in participatory planning activities.

PMID- 29179120
TI  - Metal-homeostasis in the pathobiology of the opportunistic human fungal pathogen
      Aspergillus fumigatus.
AB  - In contrast to obligate pathogens opportunistic pathogens such as Aspergillus
      fumigatus do not need a specific host to propagate or survive. However several
      characteristics of the saprophytic life-style and the selective pressure
      encountered in the primary ecological niche contribute to the virulence of A.
      fumigatus. All fungi depend on metals for growth and proliferation, like iron,
      copper, zinc, manganese or calcium. In the recent past several studies explored
      the manifold impact of metals modulating virulence of pathogens. Components which
      might be scarce in the natural environment but also in the host due to
      nutritional immunity. This review recapitulates molecular constituents of metal
      ion uptake systems in A. fumigatus, their regulation and their significance at
      the host-pathogen battlefield.

PMID- 29179121
TI  - Antibody biosensors for spoilage yeast detection based on impedance spectroscopy.
AB  - Brettanomyces is a yeast species responsible for wine and cider spoilage,
      producing volatile phenols that result in off-odors and loss of fruity sensorial
      qualities. Current commercial detection methods for these spoilage species are
      liable to frequent false positives, long culture times and fungal contamination.
      In this work, an interdigitated (IDE) biosensor was created to detect
      Brettanomyces using immunological reactions and impedance spectroscopy analysis.
      To promote efficient antibody immobilization on the electrodes' surface and to
      decrease non-specific adsorption, a Self-Assembled Monolayer (SAM) was developed.
      An impedance spectroscopy analysis, over four yeast strains, confirmed our
      device's increased efficacy. Compared to label-free sensors, antibody biosensors
      showed a higher relative impedance. The results also suggested that these
      biosensors could be a promising method to monitor some spoilage yeasts, offering
      an efficient alternative to the laborious and expensive traditional methods.

PMID- 29179122
TI  - Impacts of water quality on the corrosion of cast iron pipes for water
      distribution and proposed source water switch strategy.
AB  - Switch of source water may induce "red water" episodes. This study investigated
      the impacts of water quality on iron release, dissolved oxygen consumption
      (DeltaDO), corrosion scale evolution and bacterial community succession in cast
      iron pipes used for drinking water distribution at pilot scale, and proposed a
      source water switch strategy accordingly. Three sets of old cast iron pipe
      section (named BP, SP and GP) were excavated on site and assembled in a test
      base, which had historically transported blended water, surface water and
      groundwater, respectively. Results indicate that an increasing Cl- or SO42-
      concentration accelerated iron release, but alkalinity and calcium hardness
      exhibited an opposite tendency. Disinfectant shift from free chlorine to
      monochloramine slightly inhibited iron release, while the impact of
      peroxymonosulfate depended on the source water historically transported in the
      test pipes. The DeltaDO was highly consistent with iron release in all three pipe
      systems. The mass ratio of magnetite to goethite in the corrosion scales of SP
      was higher than those of BP and GP and kept almost unchanged over the whole
      operation period. Siderite and calcite formation confirmed that an increasing
      alkalinity and hardness inhibited iron release. Iron-reducing bacteria decreased
      in the BP but increased in the SP and GP; meanwhile, sulfur-oxidizing, sulfate
      reducing and iron oxidizing bacteria increased in all three pipe systems. To
      avoid the occurrence of "red water", a source water switch strategy was proposed
      based on the difference between local and foreign water qualities.

PMID- 29179123
TI  - Spatial and temporal variability of bacterial indicators and pathogens in six
      California reservoirs during extreme drought.
AB  - California has one of the largest systems of surface water reservoirs in the
      world, providing irrigation water to California's agriculturally productive
      Central Valley. Irrigation water is recognized as a vehicle for the microbial
      contamination of raw produce and must be monitored according to new federal
      regulation. The purpose of this study was to further understanding of the
      variability of fecal indicator bacteria (Escherichia coli and fecal coliforms)
      and pathogens (E. coli O157:H7 (O157), non-O157 Shiga toxin-producing E. coli
      (STEC) and Salmonella) along both horizontal and vertical profiles within
      California reservoirs. Monthly sampling was conducted in six reservoirs located
      in the foothills of the Western Sierra Nevada during the summer irrigation season
      and extreme drought conditions of 2014 (n = 257). Concentrations of fecal
      indicator bacteria were highly variable between reservoirs (p < 0.05) and along
      the horizontal profile (p < 0.001) from upstream to downstream, with higher
      concentrations typically found outside of the reservoirs than within. Though many
      of the reservoirs were thermally stratified, bacterial concentrations were not
      associated with water temperature (p > 0.05) or any one particular depth strata
      (p < 0.05). However, prevalence of Salmonella and STEC (16/70 and 9/70
      respectively) was higher in the deep strata than in mid or surface layers. We
      found no statistical association between samples collected downstream of
      reservoirs and those from the reservoirs themselves. Continued monitoring and
      modeling of both bacterial indicators and enteric pathogens are critical to our
      ability to estimate the risk of surface irrigation water supplies and make
      appropriate management decisions.

PMID- 29179124
TI  - Recovery of water and minerals from shale gas produced water by membrane
      distillation crystallization.
AB  - Shale gas produced water (SGPW) treatment imposes greater technical challenges
      because of its high concentration of various contaminants. Membrane distillation
      crystallization (MDC) has a great potential to manage SGPW since it is capable of
      recovering both water and minerals at high rates, up to near a zero liquid
      discharge (ZLD) condition. To evaluate the feasibility of MDC for SGPW treatment,
      MDC performance indicators, such as water recovery rate, solid production rate
      (SPR) and specific energy consumption (SEC), were systematically investigated, to
      our knowledge for the first time, by using actual SGPW from Eagle Ford Shale
      (USA). The main operating parameters including feed cross-flow velocity (CFV) and
      crystallization temperature (TCr) were optimized by performing a series of MDC
      experiments. The results reported that water and minerals were effectively
      recovered with 84% of recovery rate and 2.72 kg/m2day of SPR under respective
      optimal operating conditions. Furthermore, the scale mechanism was firstly
      identified as limiting factor for MDC performance degradation. Lastly, SEC of MDC
      was estimated to be as low as 28.2 kWh/m3 under ideal optimal operating
      conditions. Our experimental observations demonstrated that MDC could sustainably
      and effectively recover water and mineral with low energy consumption from SGPW
      by optimizing operating condition.

PMID- 29179125
TI  - Peer motivational climate and character development: Testing a practitioner
      developed youth sport model.
AB  - Youth sport is a key developmental context for many reasons, including the
      opportunities it provides for building relationships with peers and its potential
      to support character development. Peers can influence adolescent sport
      experiences and shape their motivations, and different peer motivational climates
      may differentially support athlete character. Established models identify
      different dimensions of peer motivational climate, yet these models do not
      describe how aspects of peer climate may align with character. We therefore
      assess profiles of peer motivational climate in relation to a multi-dimensional
      practitioner-developed theoretical model for character development through sport.
      Participants were 655 adolescent athletes from the greater Boston area, in the
      United States. Athletes perceiving a mastery-involved peer climate, even with
      high intra-team competition, were most likely to exhibit positive character
      attributes at the three levels of character assessed: themselves, their
      teammates, and the game. This study also demonstrates the utility of practitioner
      developed models for adolescent research.

PMID- 29179126
TI  - Adolescent health literacy and health behaviors: A systematic review.
AB  - OBJECTIVES: To systematically review and synthesize literature on the
      relationship between health literacy and health behaviors in adolescents.
      METHODS: Searches in PsychInfo, PUBMED/MEDLINE, and Educational Resources
      Information Center (ERIC) were conducted. Studies were included if they reported
      original data on the relationship between health literacy and a health behavior
      in adolescents, were written in English, and the population did not have a
      chronic illness or disability. RESULTS: Seventeen studies met inclusionary
      criteria. Definition and measurement of health literacy, and theoretical
      frameworks varied across studies. Studies investigated the relationship between
      functional and media health literacy and adolescent health behaviors, thirteen
      reported significant, linear relationships. CONCLUSIONS: The results suggest that
      there is a meaningful relationship between health literacy and adolescents'
      health behaviors. To fully understand the role of health literacy in adolescents'
      health decision-making, future research should use comprehensive definitions and
      measures of health literacy, and integrate health behavior and adolescent
      development theoretical frameworks in study design.

PMID- 29179127
TI  - From TBT to booster biocides: Levels and impacts of antifouling along coastal
      areas of Panama.
AB  - Antifouling biocides in surface sediments and gastropod tissues were assessed for
      the first time along coastal areas of Panama under the influence of maritime
      activities, including one of the world's busiest shipping zones: the Panama
      Canal. Imposex incidence was also evaluated in five muricid species distributed
      along six coastal areas of Panama. This TBT-related biological alteration was
      detected in three species, including the first report in Purpura panama. Levels
      of organotins (TBT, DBT, and MBT) in gastropod tissues and surficial sediments
      ranged from <5 to 104 ng Sn g-1 and <1-149 ng Sn g-1, respectively. In addition,
      fresh TBT inputs were observed in areas considered as moderate to highly
      contaminated mainly by inputs from fishing and leisure boats. Regarding booster
      biocides, TCMTB and dichlofluanid were not detected in any sample, while irgarol
      1051, diuron and DCOIT levels ranged from <0.08 to 2.8 ng g-1, <0.75-14.1 ng g-1,
      and <0.38-81.6 ng g-1, respectively. The highest level of TBT (149 ng Sn g-1) and
      irgarol 1051 (2.8 ng g-1), as well as relevant level of DCOIT (5.7 ng g-1), were
      detected in a marina used by recreational boats. Additionally, relatively high
      diuron values (14.1 ng g-1) were also detected in the Panama Canal associate to a
      commercial port. DCOIT concentrations were associated with the presence of
      antifouling paint particles in sediments obtained nearby shipyard or boat
      maintenance sites. The highest levels of TBT, irgarol 1051, and diuron exceeded
      international sediment quality guidelines indicating that toxic effects could be
      expected in coastal areas of Panama. Thus, the simultaneous impacts produced by
      new and old generations of antifouling paints highlight a serious environmental
      issue in Panamanian coastal areas.

PMID- 29179128
TI  - Historical legacies of river pollution reconstructed from fish scales.
AB  - Many rivers have been impacted by heavy metal pollution in the past but the long
      term legacies on biodiversity are difficult to estimate. The River Ulla (NW
      Spain) was impacted by tailings from a copper mine during the 1970-1980s but
      absence of baseline values and lack of subsequent monitoring have prevented a
      full impact assessment. We used archived fish scales of Atlantic salmon to
      reconstruct levels of historical copper pollution and its effects on salmon
      fitness. Copper bioaccumulation significantly increased over baseline values
      during the operation of the mine, reaching sublethal levels for salmon survival.
      Juvenile growth and relative population abundance decreased during mining, but no
      such effects were observed in a neighbouring river unaffected by mining. Our
      results indicate that historical copper exposure has probably compromised the
      fitness of this Atlantic salmon population to the present day, and that fish
      scales are suitable biomarkers of past river pollution.

PMID- 29179129
TI  - Multivariate statistical analysis to characterize/discriminate between
      anthropogenic and geogenic trace elements occurrence in the Campania Plain,
      Southern Italy.
AB  - Shallow aquifers are the most accessible reservoirs of potable groundwater;
      nevertheless, they are also prone to various sources of pollution and it is
      usually difficult to distinguish between human and natural sources at the
      watershed scale. The area chosen for this study (the Campania Plain) is
      characterized by high spatial heterogeneities both in geochemical features and in
      hydraulic properties. Groundwater mineralization is driven by many processes such
      as, geothermal activity, weathering of volcanic products and intense human
      activities. In such a landscape, multivariate statistical analysis has been used
      to differentiate among the main hydrochemical processes occurring in the area,
      using three different approaches of factor analysis: (i) major elements, (ii)
      trace elements, (iii) both major and trace elements. The elaboration of the
      factor analysis approaches has revealed seven distinct hydrogeochemical
      processes: i) Salinization (Cl-, Na+); ii) Carbonate rocks dissolution; iii)
      Anthropogenic inputs (NO3-, SO42-, U, V); iv) Reducing conditions (Fe2+, Mn2+);
      v) Heavy metals contamination (Cr and Ni); vi) Geothermal fluids influence (Li+);
      and vii) Volcanic products contribution (As, Rb). Results from this study
      highlight the need to separately apply factor analysis when a large data set of
      trace elements is available. In fact, the impact of geothermal fluids in the
      shallow aquifer was identified from the application of the factor analysis using
      only trace elements. This study also reveals that the factor analysis of major
      and trace elements can differentiate between anthropogenic and geogenic sources
      of pollution in intensively exploited aquifers.

PMID- 29179130
TI  - Predictive bioinformatics identifies novel regulators of proliferation in a
      cancer stem cell model.
AB  - The cancer stem cell model postulates that tumors are hierarchically organized
      with a minor population, the cancer stem cells, exhibiting unlimited
      proliferative potential. These cells give rise to the bulk of tumor cells, which
      retain a limited ability to divide. Without successful targeting of cancer stem
      cells, tumor reemergence after therapy is likely. However, identifying target
      pathways essential for cancer stem cell proliferation has been challenging. Here,
      using a transcriptional network analysis termed GAMMA, we identified 50 genes
      whose correlation patterns suggested involvement in cancer stem cell division.
      Using RNAi depletion, we found that 21 of these target genes showed preferential
      growth inhibition in a breast cancer stem cell model. More detailed initial
      analysis of 6 of these genes revealed 4 with clear roles in the fidelity of
      chromosome segregation. This study reveals the strong predictive potential of
      transcriptional network analysis in increasing the efficiency of successful
      identification of novel proliferation dependencies for cancer stem cells.

PMID- 29179131
TI  - Engineering detoxified pneumococcal pneumolysin derivative DeltaA146PLY for self
      biomineralization of calcium phosphate: Assessment of their protective efficacy
      in murine infection models.
AB  - Vaccine design ushered in the era of nanotechnology, as the vaccine is being
      developed toward particulate formulation. We have previously shown that the
      attenuated pneumolysin mutant (DeltaA146PLY) was a safe and effective
      pneumococcal vaccine candidate. Here, to further optimize the formulation, we
      fused calcium phosphate (CaP) binding domains with DeltaA146PLY so that the
      biocompatible CaP can mineralize with the protein automatically, allowing simple
      production of nanoparticle antigen during preparation. We fabricated four
      different nanoparticles, and then we compared the characteristics of different
      CaP-DeltaA146PLY nanoparticles and demonstrated the influence of CaP binding
      domains on the size, shape and surface calcium content of the nanoparticles. It
      was found that these self-biomineralized CaP-DeltaA146PLY nanoparticles varied in
      their capacity to induce BMDCs and splenocytes production of cytokines. We
      further demonstrated that, compared to free proteins, nanoparticle antigens
      induced more efficient humoral and cellular immune responses which was strong
      enough to protect mice from both pneumonia and sepsis infection. Also, the
      integration of CaP to protein has no significant impairment on body weight of
      animals, and subcutaneous injection of DeltaA146PLY-peptides@CaP nanoparticles
      did not lead to permanent formation of nodules in the skin relative to Alum
      adjuvant formulated antigens. Together, our data sufficiently suggest that
      soluble DeltaA146PLY vaccine candidate could be processed into nanoparticles by
      self-biomineralization of CaP, the immunogenicity of which could be efficiently
      improved by the CaP binding domains and biomineralization.

PMID- 29179132
TI  - Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based
      nicotine vaccine for immunotherapy against nicotine addiction.
AB  - Current clinically-tested nicotine vaccines have yet shown enhanced smoking
      cessation efficacy due to their low immunogenicity. Achieving a sufficiently high
      immunogenicity is a necessity for establishing a clinically-viable nicotine
      vaccine. This study aims to facilitate the immunogenicity of a hybrid
      nanoparticle-based nicotine vaccine by rationally incorporating toll-like
      receptor (TLR)-based adjuvants, including monophosphoryl lipid A (MPLA),
      Resiquimod (R848), CpG oligodeoxynucleotide 1826 (CpG ODN 1826), and their
      combinations. The nanoparticle-delivered model adjuvant was found to be taken up
      more efficiently by dendritic cells than the free counterpart. Nanovaccine
      particles were transported to endosomal compartments upon cellular
      internalization. The incorporation of single or dual TLR adjuvants not only
      considerably increased total anti-nicotine IgG titers but also significantly
      affected IgG subtype distribution in mice. Particularly, the nanovaccines
      carrying MPLA+R848 or MPLA+ODN 1826 generated a much higher anti-nicotine
      antibody titer than those carrying none or one adjuvant. Meanwhile, the anti
      nicotine antibody elicited by the nanovaccine adjuvanted with MPLA+R848 had a
      significantly higher affinity than that elicited by the nanovaccine carrying
      MPLA+ODN 1826. Moreover, the incorporation of all the selected TLR adjuvants
      (except MPLA) reduced the brain nicotine levels in mice after nicotine challenge.
      Particularly, the nanovaccine with MPLA+R848 exhibited the best ability to reduce
      the level of nicotine entering the brain. Collectively, rational incorporation of
      TLR adjuvants could enhance the immunological efficacy of the hybrid nanoparticle
      based nicotine vaccine, making it a promising next-generation immunotherapeutic
      candidate for treating nicotine addiction.

PMID- 29179135
TI  - No improvement in long-term survival for epithelial ovarian cancer patients: A
      population-based study between 1989 and 2014 in the Netherlands.
AB  - AIM: This study investigates changes in therapy and long-term survival for
      patients with epithelial ovarian cancer (EOC) in the Netherlands. METHODS: All
      patients with EOC, including peritoneal and fallopian tube carcinoma, diagnosed
      in the Netherlands between 1989 and 2014 were selected from the Netherlands
      Cancer Registry. Changes in therapy were studied and related to overall survival
      (OS) using multivariable Cox regression models. RESULTS: A total of 32,540
      patients were diagnosed with EOC of whom 22,047 (68%) had advanced stage disease.
      In early stage, lymph node dissection as part of surgical staging procedures
      increased over time from 4% in 1989-1993 to 62% in 2009-2014 (P < 0.001). In
      advanced stage, the number of patients receiving optimal treatment with surgery
      and chemotherapy increased from 55% in 1989-1993 to 67% in 2009-2014 (P < 0.001).
      Five-year survival rates improved in both early stage (74% versus 79%) and
      advanced stage (16% versus 24%) as well as in all patients combined (31% versus
      34%). Ten-year survival rates, however, slightly improved in early stage (62%
      versus 67%) and advanced stage (10% versus 13%) but remained essentially
      unchanged at 24% for all patients combined. CONCLUSION: Despite intensified
      treatment and staging procedures, long-term survival for women with EOC has not
      improved in the last 25 years. The observed improvements in 5-year OS reflect a
      more prolonged disease control rather than better chances for cure. Furthermore,
      the apparent better long-term outcome, when early and advanced stage patients are
      analysed separately, is largely due to improved staging procedures and the
      ensuing stage migration. These effects disappear in a combined analysis of all
      patients.

PMID- 29179133
TI  - Improved heart repair upon myocardial infarction: Combination of magnetic
      nanoparticles and tailored magnets strongly increases engraftment of myocytes.
AB  - Cell replacement in the heart is considered a promising strategy for the
      treatment of post-infarct heart failure. Direct intramyocardial injection of
      cells proved to be the most effective application route, however, engraftment
      rates are very low (<5%) strongly hampering its efficacy. Herein we combine
      magnetic nanoparticle (MNP) loading of EGFP labeled embryonic cardiomyocytes
      (eCM) and embryonic stem cell-derived cardiomyocytes (ES-CM) with application of
      custom designed magnets to enhance their short and long-term engraftment. To
      optimize cellular MNP uptake and magnetic force within the infarct area, first
      numerical simulations and experiments were performed in vitro. All tested cell
      types could be loaded efficiently with SOMag5-MNP (200 pg/cell) without toxic
      side effects. Application of a 1.3 T magnet at 5 mm distance from the heart for
      10 min enhanced engraftment of both eCM and ES-CM by approximately 7 fold at 2
      weeks and 3.4 fold (eCM) at 8 weeks after treatment respectively and also
      strongly improved left ventricular function at all time points. As underlying
      mechanisms we found that application of the magnetic field prevented the initial
      dramatic loss of cells via the injection channel. In addition, grafted eCM
      displayed higher proliferation and lower apoptosis rates. Electron microscopy
      revealed better differentiation of engrafted eCM, formation of cell to cell
      contacts and more physiological matrix formation in magnet-treated grafts. These
      results were corroborated by gene expression data. Thus, combination of MNP
      loaded cells and magnet-application strongly increases long-term engraftment of
      cells addressing a major shortcoming of cardiomyoplasty.

PMID- 29179134
TI  - A randomised phase II study of chemoradiotherapy with or without nimotuzumab in
      locally advanced oesophageal cancer: NICE trial.
AB  - PURPOSE: Chemoradiotherapy is the standard treatment for patients with inoperable
      locally advanced oesophageal cancer. We sought to assess the safety and efficacy
      of chemoradiation combined with nimotuzumab, a humanised antibody directed
      against epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Untreated
      patients with inoperable locally advanced oesophageal cancer and no distant
      metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil
      combined with external beam radiation) alone or in combination with nimotuzumab.
      The primary end-point was the endoscopic complete response (eCR) rate, and
      secondary end-points comprised quality of life (QoL) and safety. The combined eCR
      and pathologic complete response (cEPCR) and overall survival (OS) were also
      evaluated. RESULTS: We enrolled 107 patients with a mean age of 59 years, and 93%
      had squamous cell carcinoma. Toxicity was manageable in both arms with no
      important differences in adverse events (AEs). We performed post-treatment
      endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat
      population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P =
      0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02),
      respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for
      OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS
      of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm.
      Regarding QoL, a significant difference was observed for the physical subscale
      score (P = 0.03) with lower values for the control arm. CONCLUSION: Combined
      chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced
      oesophageal cancer, it appears to increase the cEPCR rate, and without
      compromising QoL. CLINICAL TRIALS: Identification number: EF024-201; Trial
      registry: NCT01249352.

PMID- 29179136
TI  - Cross-cultural psychometric assessment of the VAGUS insight into psychosis scale 
      Spanish version.
AB  - Impaired insight into illness, a core feature of schizophrenia with negative
      clinical implications, is a multidimensional phenomenon existing on a continuum.
      However, the degree to which illness perception in distinct cultures influences
      the appraisal of insight into illness in schizophrenia remains unclear. As such,
      we aimed to determine if the psychometric properties of the VAGUS insight into
      psychosis scale (www.vagusonline.com), which was originally assessed in English
      speaking Canadians, were similar in a sample of Latino Mexican Spanish speaking
      patients with schizophrenia. To accomplish this, the VAGUS - Self-Report (SR)
      version was translated from English to Spanish and psychometrically evaluated in
      95 participants. The Spanish version of the VAGUS-SR was internally consistent (?
      = 0.713), and demonstrated good convergent and discriminant validity with the
      subscales of the Positive and Negative Syndrome Scale. Factor analysis identified
      two components of insight, congruent with two of the components of the English
      version of the VAGUS-SR. In conclusion, the VAGUS-SR is a brief, novel, and valid
      measure of insight into illness in schizophrenia, which demonstrated similar
      psychometric properties in two culturally and linguistically distinct samples
      with schizophrenia. Future studies should assess whether the VAGUS demonstrates
      similar psychometric properties in non-Western cultures.

PMID- 29179137
TI  - Group Metacognitive Therapy vs. Mindfulness Meditation Therapy in a
      Transdiagnostic Patient Sample: A Randomised Feasibility Trial.
AB  - Two transdiagnostic therapies for treating psychological disorder are
      Metacognitive Therapy (MCT) and Mindfulness Based Stress Reduction (MBSR). These
      two approaches have yet to be compared and therefore the current study aimed to
      evaluate the feasibility of a study of group MCT and MBSR in treating anxiety and
      depression. A feasibility trial with 40 participants (aged 19-56) was conducted.
      Patients were randomly assigned to receive either eight weeks of group MCT or
      MBSR. The primary outcome was feasibility which included recruitment rates,
      retention and treatment acceptability. The primary symptom outcome was the
      Hospital Anxiety and Depression Scale (HADS) total score, which provided an
      overall measure of distress. Both treatments were found to be acceptable with low
      attrition and similar ratings of acceptability. Changes in outcomes were analyzed
      based on the intention-to-treat principle using mixed effect models. Preliminary
      analyses revealed that MCT was more effective in treating anxiety and depression
      in comparison to MBSR, and in reducing both positive and negative metacognitive
      beliefs. Reliable improvement rates favoured MCT at post-treatment and 6-month
      follow up. Both treatments appeared to be feasible and acceptable in treating
      transdiagnostic samples; however, a larger, definitive trial is required. The
      limitations and directions for future research are discussed.

PMID- 29179138
TI  - Pathological jealousy and pathological love: Apples to apples or apples to
      oranges?
AB  - Pathological jealousy evokes emotions, thoughts, and behaviors that cause damage
      to social and interpersonal relationships. On the other hand, pathological love
      is the uncontrollable behavior of caring for a partner that results in neglecting
      the needs of the self. The aim of the present research was to assess the
      similarities and differences between the two psychopathologies of love. To this
      end, thirty-two individuals with pathological jealousy and 33 individuals with
      pathological love were compared on demographics, aspects of romantic relationship
      (jealousy, satisfaction, love style), psychiatric co-morbidities, personality and
      psychological characteristics (e.g., impulsivity). In a univariate analysis
      individuals with pathological jealousy were more likely to be in a current
      relationship and reported greater satisfaction. The avoidant attachment and the
      ludus love style were associated with pathological jealousy whereas the secure
      attachment and agape love style was associated with pathological love. Almost
      three-quarters (72.3%) of the sample met criteria for a current psychiatric
      disorder, however no differences emerged between the pathological jealousy and
      pathological love groups. In a binary logistic regression, relationship status
      and impairments in parenting significantly differentiated the groups. While both
      pathological jealousy and pathological love share similarities, they also present
      with unique differences, which may have important treatment implications.

PMID- 29179139
TI  - A comparison of two evisceration methods on hygienic quality in the pelvic area
      of sheep carcasses.
AB  - The aim was to compare the effects of two evisceration methods under operational
      conditions, on the pelvic hygiene of sheep carcasses. Method 1: rectum sealed
      with plastic bag and pushed through the pelvic cavity. Method 2: rectum cut,
      placed back inside and pulled out from the carcass. The 18 largest Norwegian
      sheep abattoirs participated. Sampling areas were i) 400cm2 inside the pelvic
      cavity (n=623), ii) 100cm2 outside the circum-anal incision (n=622). There were
      pooled samples by swabbing the same area of five carcasses, representing totally
      3115 carcasses. Mean E. coli results from Method 1: -1.61logCFU/cm2 inside and 
      0.25logCFU/cm2 for the outside area. Results from Method 2: -1.56logCFU/cm2
      inside and -0.42logCFU/cm2 outside. There were no significant differences between
      the two methods. Both evisceration methods can produce carcasses that are of
      practically identical high hygienic quality.

PMID- 29179140
TI  - Modifying a negative interpretation bias for ambiguous social scenarios that
      depict the risk of rejection in women with anorexia nervosa.
AB  - BACKGROUND: A heightened sensitivity to social rejection might contribute towards
      the interpersonal difficulties and symptoms that characterise Anorexia Nervosa
      (AN). This paper examines the effect of Cognitive Bias Modification for
      Interpretation biases (CBM-I) training on a negative interpretation bias for
      ambiguous social scenarios that involve the risk of rejection and eating
      behaviour. METHOD: Women with AN received a single session of CBM-I training to
      develop a more benign interpretational style or a control condition (which
      included 50:50 negative and benign resolutions). To measure participant's
      interpretation bias for social stimuli, a sentence completion task was used pre
      and post-training (a near-transfer outcome measure). A test meal was given after
      the training and salivary cortisol (stress) levels were measured as far-transfer
      outcome measures. RESULTS: CBM-I training led to a significant reduction in a
      negative interpretation bias in both conditions. No effect on eating behaviour or
      stress was found, which may be expected as the training conditions did not
      significantly differ in interpretation bias change. LIMITATIONS: The control
      condition may have inadvertently reduced a negative interpretation bias as it
      involved listening to benign resolutions to ambiguous social scenarios for 50% of
      the trials. CONCLUSIONS: It is possible to modify a negative interpretation bias
      for social stimuli. To clarify the effect of CBM-I training on AN symptomatology,
      repeated, more intensive, and ecologically-valid training interventions may be
      required. This is because any change in eating behaviour may not be immediate,
      particularly in a population with a low body mass index and long-illness
      durations.

PMID- 29179141
TI  - A study of the real-world effectiveness of group psychoeducation for bipolar
      disorders: Is change in illness perception a key mediator of benefit?
AB  - BACKGROUND: Findings from efficacy trials of group psychoeducation (PE) for
      bipolar disorders (BD) led to its inclusion in evidence-based guidelines as a
      first-line mandatory treatment. However, pragmatic trials and observational
      studies are needed to determine its real-world effectiveness, impact on outcomes
      deemed important to patients and to clarify potential mediators of any benefits.
      METHODS: Individuals with BD were offered the opportunity to participate in 20h
      of PE and asked to complete pre- and post-intervention ratings of symptoms,
      knowledge about BD, medication adherence, and illness perception. A priori, two
      key patient outcomes were identified (social functioning and self-esteem); sample
      attrition due to dropout or relapse was recorded. RESULTS: Of 156 individuals who
      completed the pre-PE assessments, 103 completed the program and post-PE
      assessments. Only 4 of 53 dropouts were associated with BD relapse. Post
      intervention, the PE completers demonstrated a statistically significant
      improvement in social functioning (p = 0.003, Effect Size (ES) = 0.26) and a
      trend towards improved self-esteem (ES = 0.14). Whilst there were significant
      changes in medication adherence (p = 0.002, ES = 0.28), knowledge of BD (p <
      0.001, ES = 1.20), and illness perception (p < 0.001, ES = -0.37), mediational
      analysis demonstrated that only change in illness perception was associated to
      change in functioning (p=0.03) with no contribution from changes in knowledge of
      BD or medication adherence. CONCLUSIONS: In real-world settings, over 60%
      individuals completed 10-session course of PE. After controlling for demography
      and baseline clinical state, change in illness perception, rather than change in
      knowledge or medication adherence, emerged as a potential mediator of some
      benefits of PE.

PMID- 29179142
TI  - The relationship of person-specific eveningness chronotype, greater seasonality,
      and less rhythmicity to suicidal behavior: A literature review.
AB  - BACKGROUND: Epidemiological data have demonstrated seasonal and circadian
      patterns of suicidal deaths. Several reviews and meta-analyses have confirmed the
      relationship between sleep disturbance and suicidality. However, these
      reviews/meta-analyses have not focused on seasonal and circadian dysfunction in
      relation to suicidality, despite the common presence of this dysfunction in
      patients with mood disorders. Thus, the current literature review analyzed
      studies investigating person-specific chronotype, seasonality, and rhythmicity in
      relation to suicidal thoughts and behaviors. METHODS: Study authors reviewed
      articles related to individual-level chronotype, seasonality, and rhythmicity and
      suicidality that were written in English and not case reports or reviews.
      RESULTS: This review supports a relationship between an eveningness chronotype,
      greater seasonality, and decreased rhythmicity with suicidal thoughts and
      behaviors in those with unipolar depression, as well as in other psychiatric
      disorders and in children/adolescents. LIMITATIONS: These findings need to be
      explored more fully in mood disordered populations and other psychiatric
      populations, in both adults and children, with objective measurement such as
      actigraphy, and with chronotype, seasonality, and rhythmicity as well as broader
      sleep disturbance measurement all included so the construct(s) most strongly
      linked to suicidality can be best identified. CONCLUSIONS: Eveningness, greater
      seasonality, and less rhythmicity should be considered in individuals who may be
      at risk for suicidal thoughts and behaviors and may be helpful in further
      tailoring assessment and treatment to improve patient outcome.

PMID- 29179144
TI  - The centrality of DSM and non-DSM depressive symptoms in Han Chinese women with
      major depression.
AB  - INTRODUCTION: We compared DSM-IV criteria for major depression (MD) with
      clinically selected non-DSM criteria in their ability to represent clinical
      features of depression. METHOD: We conducted network analyses of 19 DSM and non
      DSM symptoms of MD assessed at personal interview in 5952 Han Chinese women
      meeting DSM-IV criteria for recurrent MD. We estimated an Ising model (the state
      of-the-art network model for binary data), compared the centrality
      (interconnectedness) of DSM-IV and non-DSM symptoms, and investigated the
      community structure (symptoms strongly clustered together). RESULTS: The DSM and
      non-DSM criteria were intermingled within the same symptom network. In both the
      DSM-IV and non-DSM criteria sets, some symptoms were central (highly
      interconnected) while others were more peripheral. The mean centrality of the DSM
      and non-DSM criteria sets did not significantly differ. In at least two cases,
      non-DSM criteria were more central than symptomatically related DSM criteria:
      lowered libido vs. sleep and appetite changes, and hopelessness versus
      worthlessness. The overall network had three sub-clusters reflecting
      neurovegetative/mood symptoms, cognitive changes and anxiety/irritability.
      LIMITATIONS: The sample were severely ill Han Chinese females limiting
      generalizability. CONCLUSIONS: Consistent with prior historical reviews, our
      results suggest that the DSM-IV criteria for MD reflect one possible sub-set of a
      larger pool of plausible depressive symptoms and signs. While the DSM criteria on
      average perform well, they are not unique and may not be optimal in their ability
      to describe the depressive syndrome.

PMID- 29179143
TI  - Factors associated with postpartum depression in women from low socioeconomic
      level in Argentina: A hierarchical model approach.
AB  - PURPOSE: to estimate the prevalence of depression at 4-week postpartum using the
      Edinburgh postpartum Depression Scale (EPDS) in women who delivered in a public
      maternity hospital in Argentina. METHODS: This prospective cohort study was
      carried out from March to August 2016 in northwest Argentina. Eligibility
      included delivering a singleton live birth 28 weeks of gestational age or over,
      18 years or older and resided within 1h from the maternity hospital. Women were
      excluded if they or their newborn were in the intensive care unit. We defined a
      positive screening as an EPDS score of 10 or higher or a positive response to
      item 10, which indicates thoughts of self-harm. RESULTS: A total of 587 women
      were enrolled and 539 women completed the home visit interview and the EPDS. A
      total of 167 (31.0%, 95% CI 27.1-35.1) mothers screened positive in the EPDS
      using a score >= 10 and 99 (18.4%, 95% CI 15.1-21.6%) using a score >= 13, which
      indicate increased severity of depressive symptoms. In both cases, the 23 (4.3%)
      women that responded as having thoughts of self-harm were included. CONCLUSION:
      Nearly a third of women who participated had depressive symptoms at four weeks
      postpartum in a public hospital in Tucuman, Argentina. Socio-demographic,
      particularly personal psychiatric history, factors and social and cultural
      influences can impact results. Our results highlight the need for improved
      screening and better diagnostic tool for women with postpartum depression in
      Argentina and to investigate the impact of postpartum depressive symptoms on
      women's health and their families.

PMID- 29179145
TI  - Investigating the performance of three modified activated sludge processes
      treating municipal wastewater in organic pollutants removal and toxicity
      reduction.
AB  - This study investigated the treatment performance of three types of modified
      activated sludge processes, i.e., anoxic/oxic (A/O), anaerobic/anoxic/oxic (A2/O)
      and oxidation ditch process, in treating municipal wastewater by measuring
      physicochemical and spectroscopic parameters, and the toxicity of the influents
      and effluents collected from 8 full-scale municipal wastewater treatment plants
      (MWTPs). The relationships between spectroscopic and physicochemical parameters
      of the wastewater samples and the applicability of the nematode Caenorhabditis
      elegans (C. elegans) bioassays for the assessment of the toxic properties of
      municipal wastewater were also evaluated. The results indicated that the
      investigated MWTPs employing any of A/O, A2/O and oxidation ditch processes could
      effectively control the discharge of major wastewater pollutants including
      biochemical oxygen demand (BOD), chemical oxygen demand, nitrogen and phosphorus.
      The oxidation ditch process appeared to have the advantage of removing tyrosine
      like substances and presented slightly better removal efficiency of tryptophan
      like fluorescent (peak T) substances than the A/O and A2/O processes. Both
      ultraviolet absorbance at 254nm and peak T may be used to characterize the
      organic load of municipal wastewater, and peak T can be adopted as a gauge of the
      BOD removal efficacy of municipal wastewater treatment. Using C. elegans-based
      oxygen consumption rate assay for monitoring municipal wastewater toxicity
      deserves further investigations.

PMID- 29179146
TI  - Copper interactions on arsenic bioavailability and phytotoxicity in soil.
AB  - Arsenic (As) and copper (Cu) are co-contaminants in the environment but little is
      known about their ecological impact as mixtures in soil. In this study, we
      investigated the combined As-Cu interactions on toxicity and uptake as binary
      mixtures in 5 contrasting soils. The study included solubility, contaminant
      uptake and toxicity in cucumber (Cucumis sativus L.) as a model plant species.
      Soils were spiked individually and as a mixtures at 10 different As levels (2, 4,
      8 up to 1024mgkg-1). Copper was added with As at two effective concentration
      levels (EC10Cu and EC50Cu). Arsenic uptake was significantly reduced in the
      presence of Cu and a higher effect was demonstrated with increasing pore-water
      pH. Copper accumulation was not significantly influenced by As. An additive
      response on plant growth was predominant overall when expressed from pore-water
      parameters with root mean square errors of 12.6 and 13.2 for EC10Cu and EC50Cu
      treatments, respectively.

PMID- 29179147
TI  - Digital gene expression analysis in the gills of Ruditapes philippinarum exposed
      to short- and long-term exposures of ammonia nitrogen.
AB  - Previous study revealed severe toxic effects of ammonia nitrogen on Ruditapes
      philippinarum including lysosomal instability, disturbed metabolic profiles, gill
      tissues with damaged structure, and variation of neurotransmitter concentrations.
      However, the underlying molecular mechanism was not fully understood yet. In the
      present study, digital gene expression technology (DGE) was applied to globally
      screen the key genes and pathways involved in the responses to short- and long
      term exposures of ammonia nitrogen. Results of DGE analysis indicated that short
      term duration of ammonia exposure affected pathways in Dorso-ventral axis
      formation, Notch signaling, thyroid hormone signaling and protein processing in
      endoplasmic reticulum. The long-term exposure led to DEGs significantly enriched
      in gap junction, immunity, signal and hormone transduction, as well as key
      substance metabolism pathways. Functional research of significantly changed DEGs
      suggested that the immunity of R. philippinarum was weakened heavily by toxic
      effects of ammonia nitrogen, as well as neuro-transduction and metabolism of
      important substances. Taken together, the present study provides a molecular
      support for the previous results of the detrimental toxicity of ammonia exposure
      in R. philippinarum, further work will be performed to investigate the specific
      genes and their certain functions involved in ammonia toxicity to molluscs.

PMID- 29179148
TI  - Systemic response of the stony coral Pocillopora damicornis against acute cadmium
      stress.
AB  - Heavy metals have become one of the main pollutants in the marine environment and
      a major threat to the growth and reproduction of stony corals. In the present
      study, the density of symbiotic zooxanthellae, levels of crucial physiological
      activities and the transcriptome were investigated in the stony coral Pocillopora
      damicornis after the acute exposure to elevated cadmium concentration. The
      density of symbiotic zooxanthellae decreased significantly during 12-24h period,
      and reached lowest at 24h after acute cadmium stress. No significant changes were
      observed in the activity of glutathione S-transferase during the entire stress
      exposure. The activities of superoxide dismutase and catalase, and the
      concentration of glutathione decreased significantly, but the activation level of
      caspase3 increased significantly after cadmium exposure. Furthermore,
      transcriptome sequencing and bioinformatics analysis revealed 3538 significantly
      upregulated genes and 8048 significantly downregulated genes at 12h after the
      treatment. There were 12 overrepresented GO terms for significantly upregulated
      genes, mostly related to unfolded protein response, endoplasmic reticulum stress
      and apoptosis. In addition, a total of 32 GO terms were overrepresented for
      significantly downregulated genes, and mainly correlated with macromolecular
      metabolic processes. These results collectively suggest that acute cadmium stress
      could induce apoptosis by repressing the production of the antioxidants,
      elevating oxidative stress and activating the unfolded protein response. This
      cascade of reactions would result to the collapse of the coral-zooxanthella
      symbiosis and the expulsion of symbiotic zooxanthellae in the stony coral P.
      damicornis, ultimately leading to coral bleaching.

PMID- 29179149
TI  - Differential response between histological and biochemical biomarkers in the
      apple snail Pomacea canaliculata (Gasteropoda: Amullariidae) exposed to
      cypermethrin.
AB  - To develop effective programs to monitor water quality is necessary to identify
      sensitive biomarkers in indicator species. The aim of this study was to evaluate
      different biomarkers in the apple snail Pomacea canaliculata exposed to the
      insecticide Cypermethrin (CYP). Adult male and female snails were exposed to
      sublethal CYP concentrations (10, 25 and 100MUgl-1) for 1, 4, 7 and 14days. The
      recovery of the exposed snails was also studied by a post-exposure assay. The
      activities of the enzymes superoxide dismutase (SOD), catalase (CAT) and
      glutathione-S-transferase (GST), the levels of lipid peroxidation (LPO) and
      protein oxidation (PC) in digestive gland and gills were studied as biomarkers of
      exposure. Histopathological changes in target tissues were also evaluated. In
      digestive gland, CYP caused a significant increase in SOD, CAT and GST activities
      compared to control (p<0.05) as well as in LPO and PC levels (p<0.05). However,
      such biochemical effects were neither concentration nor time dependent.
      Histopatological changes were observed in the exposed groups, such as an increase
      in the number of basophilic cells, hemocytic infiltration and epithelia atrophy.
      Additionally, a positive correlation between the surface occupied by pigmented
      corpuscles and CYP concentrations was observed at all exposure periods. Gills
      showed greater sensitivity to oxidative damage than digestive gland. CYP caused
      an acute toxic effect in LPO levels in this respiratory organ. The gill filament
      of exposed snails, exhibited a reduction or loss of cilia, vacuolization of the
      columnar cells and an increase in haemocyte content irrespective of the
      concentration. High concentrations of CYP caused disruptions in the columnar
      muscle fibers. In general, snails did not show an improvement in their basal
      state during post-exposure treatment. Apparently, males and females do not have
      differential sensitivity to the pesticide. The results of this study suggest that
      histopathological changes are the most sensitive time- and dose-dependent
      biomarkers of toxicity induced by CYP in P. canaliculata.

PMID- 29179151
TI  - Photomixotrophic chemical production in cyanobacteria.
AB  - The current global dependence on fossil fuels for both energy and chemical
      production has spurred concerns regarding long-term resource security and
      environmental detriments resulting from increased CO2 levels. Through the
      installation of exogenous metabolic pathways, engineered cyanobacteria strains
      can directly fix CO2 into industrially relevant chemicals currently produced from
      petroleum. This review highlights some of the studies that have successfully
      implemented photomixotrophic conditions to increase cyanobacterial chemical
      production. Supplementation with fixed carbon sources provides additional carbon
      building blocks and energy to enhance production and occasionally aid in growth.
      Photomixotrophic production has increased titers up to 5-fold over traditional
      autotrophic conditions, demonstrating promising applications for future
      commercialization.

PMID- 29179150
TI  - Effect of imidacloprid on the survival of Xenopus tadpoles challenged with wild
      type frog virus 3.
AB  - The sensitivity of amphibians to Ranavirus may be increased by exposure to other
      environmental stressors, including chemical contaminants. Neonicotinoid
      insecticides comprise 27% of the global insecticide market and have been detected
      in wetlands and other aquatic habitats. The present study focused on the effects
      of exposure of pre-metamorphic Xenopus laevis to the neonicotinoid, imidacloprid
      (IMI) on sensitivity to frog virus 3 (FV3) infection. It was hypothesized that
      exposure of tadpoles to IMI at sublethal concentrations of 1 and 500MUgL-1 would
      increase FV3 related mortalities relative to tadpole mortalities in a control
      treatment with only the virus. However, contrary to the predicted outcome, IMI
      reduced the rates of mortality following viral challenge, although the total
      mortalities by the 25th day after infection did not differ among the treatments.
      These results should not be interpreted as an indication that neonicotinoid
      insecticides are beneficial to aquatic ecosystems, since these insecticides cause
      toxic responses at low concentrations to other non-target aquatic organisms.

PMID- 29179152
TI  - Region stability analysis and tracking control of memristive recurrent neural
      network.
AB  - Memristor is firstly postulated by Leon Chua and realized by Hewlett-Packard (HP)
      laboratory. Research results show that memristor can be used to simulate the
      synapses of neurons. This paper presents a class of recurrent neural network with
      HP memristors. Firstly, it shows that memristive recurrent neural network has
      more compound dynamics than the traditional recurrent neural network by
      simulations. Then it derives that n dimensional memristive recurrent neural
      network is composed of [Formula: see text] sub neural networks which do not have
      a common equilibrium point. By designing the tracking controller, it can make
      memristive neural network being convergent to the desired sub neural network. At
      last, two numerical examples are given to verify the validity of our result.

PMID- 29179153
TI  - Reduced-order state estimation of delayed recurrent neural networks.
AB  - Different from the widely-studied full-order state estimator design, this paper
      focuses on dealing with the reduced-order state estimation problem for delayed
      recurrent neural networks. By employing an integral inequality, a delay-dependent
      design approach is proposed, and global asymptotical stability of the resulting
      error system is guaranteed. It is shown that the gain matrix of the reduced-order
      state estimator is determined by the solution of a linear matrix inequality.
      Numerical examples are provided to illustrate the effectiveness of the developed
      result.

PMID- 29179154
TI  - Understanding sexual assault risk perception in college: Associations among
      sexual assault history, drinking to cope, and alcohol use.
AB  - INTRODUCTION: Sexual assault history and alcohol use are associated with higher
      likelihood of subsequent sexual assault. Alcohol use and drinking to cope are
      associated with re-assault, but it is unclear whether these factors are
      associated with malleable constructs like sexual assault risk perception. This
      study examined typical weekly drinking and drinking to cope motive as factors
      underlying the association between sexual assault history and risk perception.
      METHODS: Both perceived likelihood of experiencing incapacitated sexual assault
      and when to leaving a hypothetical sexual assault scenario were assessed as
      indicators of sexual assault risk perception. 660 female college students
      recruited from psychology courses completed questionnaires online. RESULTS:
      Results revealed that sexual assault history severity was positively associated
      with perceived incapacitated sexual assault likelihood and when to leave a risky
      scenario. Drinking to cope with anxiety was positively associated with perceived
      incapacitated sexual assault likelihood. Among women who reported regular
      drinking, typical weekly drinking was positively associated with when to leave a
      risky scenario, such that women who reported more weekly drinks stayed in a
      potentially risky scenario longer than women who reported fewer weekly drinks.
      CONCLUSIONS: These findings suggest that alcohol use and drinking to cope with
      anxiety are associated with risk perception. Sexual assault history was
      associated with both perceived incapacitated sexual assault likelihood and when
      to leave a hypothetical scenario. Alcohol use and drinking to cope are two
      potential points of intervention for sexual assault risk reduction programs, but
      further examination is needed.

PMID- 29179155
TI  - Patterns of adverse childhood experiences and substance use among young adults: A
      latent class analysis.
AB  - INTRODUCTION: Adverse childhood experiences (ACEs) have been strongly linked with
      subsequent substance use. The aim of this study was to investigate how different
      patterns of ACEs influence substance use in young adulthood. METHODS: Using a
      community sample of young individuals (N=336; ages 18-25), we performed latent
      class analyses (LCA) to identify homogenous groups of young people with similar
      patterns of ACEs. Exposure to ACEs incorporates 13 childhood adversities
      including childhood maltreatment, household dysfunction, and community violence.
      Multiple linear and logistic regression models were used in an effort to examine
      the associations between ACEs classes and four young adult outcomes such as
      alcohol-related problems, current tobacco use, drug dependence symptoms, and
      psychological distress. RESULTS: LCA identified four heterogeneous classes of
      young people distinguished by different patterns of ACEs exposure: Low ACEs
      (56%), Household Dysfunction/Community Violence (14%), Emotional ACEs (14%), and
      High/Multiple ACEs (16%). Multiple regression analyses found that compared to
      those in the Low ACEs class, young adults in the High/Multiple ACEs class
      reported more alcohol-related problems, current tobacco use, and psychological
      symptoms, controlling for sociodemographic characteristics and common risk
      factors for substance use such as peer substance use. CONCLUSIONS: Our findings
      confirm that for many young people, ACEs occur as multiple rather than single
      experiences. The results of this research suggest that exposure to poly
      victimization during childhood is particularly related to substance use during
      young adulthood.

PMID- 29179157
TI  - Measurement of the bone endocortical region using clinical CT.
AB  - The extent of the endocortical region and cortical bone mineral density (cBMD)
      throughout the proximal femur are of interest as both have been linked to
      fracture risk and osteoporosis treatment response. Non-invasive in-vivo clinical
      CT-based techniques capable of measuring the cortical bone attributes of
      thickness, density and mass over a bone surface have already been proposed.
      Several studies have robustly shown these methods to be capable of producing
      cortical thickness measurements to a sub-millimetre accuracy. Unfortunately,
      these methods are unable to provide high quality cBMD estimates, and are not
      designed to measure any attributes over the endocortical region of cortical bone.
      In this paper, we develop a cortical bone mapping based technique capable of
      providing an improved cBMD estimate and a measure of the endocortical width,
      while maintaining similar quality cortical thickness and trabecular bone mineral
      density (tBMD) estimates. The performance of the technique was assessed using a
      paired dataset of ex-vivo QCT and HR-pQCT scans across 72 proximal femurs. The HR
      pQCT scans were analysed using a new method developed for this study: high
      resolution tissue classification (HRTC). In HRTC the cortical, endocortical and
      sub-surface trabecular bone features are extracted from the partially resolvable
      microarchitectural details in the HR-pQCT scan. We demonstrate that measurement
      of the endocortical extent from QCT is possible with an accuracy of -0.15+/
      0.71mm, and that local cBMD can be measured down to densities of 300 mg/cm3.

PMID- 29179158
TI  - Modelling nonlinearity of guided ultrasonic waves in fatigued materials using a
      nonlinear local interaction simulation approach and a spring model.
AB  - Modelling and numerical simulation - based on the framework of the Local
      Interaction Simulation Approach - was developed to have more insight into
      nonlinear attributes of guided ultrasonic waves propagating in fatigued metallic
      materials. Various sources of nonlinearity were considered in this modelling
      work, with particular emphases on higher-order harmonic generation and
      accumulation of nonlinearity along wave propagation. The material hyper
      elasticity was considered in the model using an energy density approach based on
      the Landau-Lifshitz formulation; and the "breathing" motion pattern of a fatigue
      crack in the material was interrogated using a spring model. Upon the successful
      validation with the model prepared in the commercial software based on the Finite
      Element Methods, two scenarios were comparatively investigated, i.e. the lower
      and higher frequency regime. In the first case propagation of a basic symmetric
      mode pair was simulated using the model to observe a cumulative characteristic of
      the second harmonic mode with nonlinear hyper-elastic material definition upon
      appropriate selection of excitation frequency. In the second case, the higher
      order symmetric mode pair was excited according to the "internal resonance"
      conditions, revealing a strong dependence of manifested nonlinearity on numerical
      parameters. Moreover, it was shown that with the use of the wave from the low
      frequency regime it was easier to differentiate later stages of the crack
      development, being in contrary to waves in the high frequency regime, which
      allowed to clearly observe early stages of the crack expansion. Such outcome lays
      the foundation to develop the damage detection and monitoring scheme in the field
      of Structural Health Monitoring based on utilising the nonlinear features of
      guided ultrasonic waves.

PMID- 29179156
TI  - Radiosensitization with an inhibitor of poly(ADP-ribose) glycohydrolase: A
      comparison with the PARP1/2/3 inhibitor olaparib.
AB  - Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add
      multiple ADP-ribose subunits to themselves and other acceptor proteins.
      Inhibitors of PARPs have become an exciting and real prospect for monotherapy and
      as sensitizers to ionising radiation (IR). The action of PARPs are reversed by
      poly(ADP-ribose) glycohydrolase (PARG). Until recently studies of PARG have been
      limited by the lack of an inhibitor. Here, a first in class, specific, and cell
      permeable PARG inhibitor, PDD00017273, is shown to radiosensitize. Further,
      PDD00017273 is compared with the PARP1/2/3 inhibitor olaparib. Both olaparib and
      PDD00017273 altered the repair of IR-induced DNA damage, resulting in delayed
      resolution of RAD51 foci compared with control cells. However, only PARG
      inhibition induced a rapid increase in IR-induced activation of PRKDC (DNA-PK)
      and perturbed mitotic progression. This suggests that PARG has additional
      functions in the cell compared with inhibition of PARP1/2/3, likely via reversal
      of tankyrase activity and/or that inhibiting the removal of poly(ADP-ribose)
      (PAR) has a different consequence to inhibiting PAR addition. Overall, our data
      are consistent with previous genetic findings, reveal new insights into the
      function of PAR metabolism following IR and demonstrate for the first time the
      therapeutic potential of PARG inhibitors as radiosensitizing agents.

PMID- 29179159
TI  - CNTNAP2 mutations and autosomal dominant epilepsy with auditory features.
AB  - Autosomal dominant epilepsy with auditory features (ADEAF) is clinically
      characterized by focal seizures with prominent auditory or aphasic auras and
      absence of structural brain abnormalities. Mutations in LGI1 and RELN genes
      account for the disorder in about 50% of ADEAF families. In a recent paper, a
      heterozygous intragenic deletion in the CNTNAP2 gene has been associated to ADEAF
      in a single family. We screened 28 ADEAF families for mutations in CNTNAP2 by
      next generation sequencing and copy number variation analyses and found no likely
      pathogenic mutations segregating with the disease. CNTNAP2 should be screened in
      genetically unsolved ADEAF families, but causative mutations are expected to be
      infrequent in this gene.

PMID- 29179160
TI  - Estimation of different source contributions to sediment organic matter in an
      agricultural-forested watershed using end member mixing analyses based on stable
      isotope ratios and fluorescence spectroscopy.
AB  - The two popular source tracing tools of stable isotope ratios (delta13C and
      delta15N) and fluorescence spectroscopy were used to estimate the relative source
      contributions to sediment organic matter (SeOM) at five different river sites in
      an agricultural-forested watershed (Soyang Lake watershed), and their
      capabilities for the source assignment were compared. Bulk sediments were used
      for the stable isotopes, while alkaline extractable organic matter (AEOM) from
      sediments was used to obtain fluorescent indices for SeOM. Several source
      discrimination indices were fully compiled for a range of the SeOM sources
      distributed in the catchments of the watershed, which included soils, forest
      leaves, crop (C3 and C4) and riparian plants, periphyton, and organic
      fertilizers. The relative source contributions to the river sediment samples were
      estimated via end member mixing analysis (EMMA) based on several selected
      discrimination indices. The EMMA based on the isotopes demonstrated that all
      sediments were characterized by a medium to a high contribution of periphyton
      ranging from ~30% to 70% except for one site heavily affected by forest and
      agricultural fields with relatively high contributions of terrestrial materials.
      The EMMA based on fluorescence parameters, however, did not show similar results
      with low contributions from forest leaf and periphyton. The characteristics of
      the studied watershed were more consistent with the source contributions
      determined by the isotope ratios. The discrepancy in the EMMA capability for
      source assignments between the two analytical tools can be explained by the
      limited analytical window of fluorescence spectroscopy for non-fluorescent
      dissolved organic matter (FDOM) and the inability of AEOM to represent original
      bulk particulate organic matter (POM).

PMID- 29179161
TI  - [Basic concept of bone remodeling.]
AB  - Bone remodeling is a fundamental mechanism of bone metabolism in tissue level.
      Bone remodeling demonstrates sequential phase of activation, resorption,
      reversal, and formation. Bone histomorphometry can make the quantitative
      assessment of the turnover in bone remodeling.

PMID- 29179162
TI  - [The role of osteoclastic bone resorption on bone remodeling.]
AB  - Bone remodeling consists of bone resorbing cycle and bone forming cycle to
      maintain bone volume and calcium homeostasis thought life. The main cells
      involves in bone remodeling are osteoclasts and osteoblasts. Bone resorption and
      bone formation are tightly coupled during bone remodeling, an imbalance of these
      two processes leads to either increased or decreased bone mass. Osteoclasts are
      multinucleated cells responsible for physiological and pathological bone
      resorption and thereby play an essential role in maintaining bone volume and
      homeostasis. Osteoclastic bone resorption is regulated by several cytokines,
      calcium signal, and transcription factors etc. Recent molecular dissection of
      genetic disorders of high increased or decreased bone mass has proven many of the
      crucial molecules controlling the osteoclastic bone resorption. This article
      reviews recent findings of molecular mechanism regarding to osteoclastic bone
      resorption to regulate bone remodeling.

PMID- 29179163
TI  - [The role of osteocytes in bone remodeling.]
AB  - Bone remodeling has important roles in the functions of bone tissues, such as
      supporting the body and mineral storage. Osteocytes, which are the most abundant
      cells in bone tissues, detect the mechanical loading and regulate both bone
      formation by osteoblasts and bone resorption by osteoclasts. However, its
      mechanism is still unknown. In this review, we summarize how osteocytes detect
      mechanical stress and discuss the potential role of CCN2/CTGF as a novel bone
      remodeling factor produced by osteocytes.

PMID- 29179164
TI  - [Coupling of bone resorption and formation.]
AB  - Preceding bone resorption is a prerequisite for the initiation of subsequent bone
      formation during adulthood and the quantity as well as the quality of bone is
      maintained by which newly formed bone by osteoblasts replaces precisely the
      amount removed by osteoclastic bone resorption at the same level. This process is
      namely " bone remodeling " and the rely of bone formation in response to
      resorption is termed " coupling " . Importantly, bone formation is induced by
      osteoclastic bone resorption or the presence of osteoclasts themselves in the
      bone remodeling. Recently, emerging evidence points to the involvement of factors
      secreted or presented by osteoclasts themselves in the coupling process. Thus,
      coupling mechanisms involved in the bone remodeling are critical for
      understanding of bone physiology and metabolic bone diseases such as
      osteoporosis.

PMID- 29179165
TI  - [Bone remodeling and modeling/mini-modeling.]
AB  - Modeling, adapting structures to loading by changing bone size and shapes, often
      takes place in bone of the fetal and developmental stages, while bone remodeling
      replacement of old bone into new bone-is predominant in the adult stage. Modeling
      can be divided into macro-modeling(macroscopic modeling)and mini
      modeling(microscopic modeling). In the cellular process of mini-modeling, unlike
      bone remodeling, bone lining cells, i.e., resting flattened osteoblasts covering
      bone surfaces will become active form of osteoblasts, and then, deposit new bone
      onto the old bone without mediating osteoclastic bone resorption. Among the drugs
      for osteoporotic treatment, eldecalcitol(a vitamin D3 analog)and
      teriparatide(human PTH[1-34])could show mini-modeling based bone formation.
      Histologically, mature, active form of osteoblasts are localized on the new bone
      induced by mini-modeling, however, only a few cell layer of preosteoblasts are
      formed over the newly-formed bone, and accordingly, few osteoclasts are present
      in the region of mini-modeling. In this review, histological characteristics of
      bone remodeling and modeling including mini-modeling will be introduced.

PMID- 29179166
TI  - [Immobilization and bone remodeling disorder.]
AB  - Mechanical stress is essential for us to maintain bone volume and structure.
      Immobilization and unloading, such as motor paralysis, long-term bedrest and
      casting of fractured area, cause rapidly remarkable bone loss. The bone
      remodeling disorder following immobilization demonstrates the acceleration of
      bone resorption and the suppression of bone formation, and molecular mechanism of
      the bone remodeling disorder has been gradually revealed recently. It is very
      difficult for us to improve the bone loss due to disuse completely. Thus,
      prevention of disuse osteoporosis is important. We should choose suitable
      treatment after considering the pathophysiology of disuse osteoporosis, and
      attempt early intervention as soon as possible.

PMID- 29179167
TI  - [Glucocorticoid-induced abnormality in bone remodeling.]
AB  - Glucocorticoid(GC)is widely used to treat a variety of autoimmune, inflammatory
      and allergic diseases. GC causes a number of adverse effects and among them
      osteoporosis and degenerative bone fracture are major complications of GC
      therapy. GC inhibits differentiation of mesenchymal stem cells to osteoblasts,
      induces apoptosis of osteoblasts and osteocytes and prolongs lifespan of
      osteoclast, resulting in low bone mass and micro-architectural deterioration of
      bone tissue, which leads to severe osteoporosis, increased bone fragility and
      susceptibility to bone fracture. Physicians who prescribe GC have to manage
      patients according to guidelines on the management and treatment of GC-induced
      osteoporosis.

PMID- 29179168
TI  - [The impact of controlling bone remodeling in rheumatoid arthritis.]
AB  - Rheumatoid arthritis(RA)is associated with increased bone turnover and early bone
      loss, which lead to increased fracture risk and progressive joint destruction.
      Pro-inflammatory cytokines, such as IL(interleukin)-17, TNF-alpha(tumor necrosis
      factor alpha), IL-1, and IL-6 induce the expression of RANKL(receptor activation
      of nuclear factor kappaB ligand)from synovial fibroblasts. RANKL promotes
      osteoclasts differentiation and activation, and Denosumab, an anti-RANKL
      monoclonal antibody, inhibits both systemic bone loss and focal bone erosion of
      RA.

PMID- 29179169
TI  - [Bone remodeling through a phosphate metabolism.]
AB  - Phosphorus is the second abundant mineral stored in bones, and disturbance of
      phosphate metabolisms results in various disease developments such as
      hypophosphatemic rickets. Blood phosphorus levels are regulated by dietary intake
      or its absorption from intestine, proximal tubular reabsorption, and number of
      factors plays roles for maintaining phosphate homeostasis. Vitamin D stimulates
      intestinal phosphorus absorption, and phosphorus promotes FGF23 secretion from
      osteocytes. FGF23 inhibits Cyp27b1, an enzyme to produce an active vitamin D3,
      1,25(OH)2D3, through FGF receptor/Klotho complex. In this review, I will discuss
      about the roles of Enpp1 in regulating the FGF23-Klotho-vitamin D axis and bones.

PMID- 29179170
TI  - [Osteoimmunology by innate immune cells.]
AB  - A hematopoietic tissue, bone marrow, is located inside the bone. The functional
      interaction between skeletal and hematopoietic systems has been revealed
      recently. The roles of osteoblasts as a component of hematopoietic
      microenvironment have been intensively studied, which is now an important
      research field. On the other hand, the functions of hematopoietic cells as
      regulators of osteoblasts have also been elucidated gradually. This review
      describes how innate immune cells such as macrophages and neutrophils take part
      in bone metabolism.

PMID- 29179171
TI  - [Aberrant bone remodeling during sepsis.]
AB  - Sepsis is a systemic inflammatory response syndrome that occurs upon severe
      bacterial infection. Although the development of early treatment for sepsis
      improves the survival rate of sepsis patients, in the subacute phase, certain
      patients suffer from secondary infection due to immunosuppression. It has been
      reported that one of the causes of the immunocompromised state during sepsis is
      lymphopenia. However, the underlying mechanisms are not well understood. We found
      that acute inflammation induced the immunodeficiency caused by the reduction of
      the numbers of peripheral lymphocytes and common lymphoid progenitors(CLPs)in the
      bone marrow, which was associated with a dramatic decrease in the osteoblast
      number. Osteoblast-specific deletion of IL-7 provided evidence for the role of
      osteoblasts in the regulation of lymphopoiesis in systemic inflammation. An acute
      loss of osteoblasts in sepsis induced the disturbance of lymphocyte homeostasis,
      resulting in immunodeficiency.

PMID- 29179172
TI  - [Control of bone remodeling by bone anabolic drugs.]
AB  - Teriparatide is a bone anabolic drug that is only available in practice. It is a
      N-terminal fragment of parathyroid hormone(PTH). Mode of actions of teriparatide
      is pharmacological but not physiological as it is administered to patients with
      osteoporosis. Physicians need to understand the fact that treatment with
      teriparatide is not just like a hormone replacement but its effects on bone
      remodeling are pharmacological. Romosozumab, under clinical development as anti
      osteoporosis drug, is a monoclonal antibody against sclerostin. Clinical data
      demonstrate that it temporally, but robustly activates bone formation as well as
      inhibits bone resorption. Thus, romosozumab is expected to have a strong anabolic
      action on bone remodeling.

PMID- 29179173
TI  - [Regulation of bone remodeling by anti-resorptives.]
AB  - Classical anti-resorptives such as bisphosphonates inhibit remodeling, leading to
      decreases in both bone resorption and formation markers. Changes in these markers
      are useful in predicting future bone mineral density and fracture risk to some
      extent. More recently developed drugs such as denosumab and odanacatib, which
      also fall into the category of anti-resorptives, show unique effects on modeling
      and remodeling. This overview summarizes action of anti-resorptives from a
      viewpoint of remodeling.

PMID- 29179174
TI  - [Current advances and future prospects of genome editing technology in the field
      of biomedicine.]
AB  - Genome editing technology can alter the genomic sequence at will, contributing
      the creation of cellular and animal models of human diseases including hereditary
      disorders and cancers, and the generation of the mutation-corrected human induced
      pluripotent stem cells for ex vivo regenerative medicine. In addition, novel
      approaches such as drug development using genome-wide CRISPR screening and cancer
      suppression using epigenome editing technology, which can change the epigenetic
      modifications in a site-specific manner, have also been conducted. In this
      article, I summarize the current advances and future prospects of genome editing
      technology in the field of biomedicine.

PMID- 29179175
TI  - Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43
      Mediated Hypoxic Postconditioning.
AB  - BACKGROUND/AIMS: Previous studies have shown that heat shock protein 90 (HSP90)
      mediated mitochondrial import of connexin 43 (Cx43) is critical in
      preconditioning cardioprotection. The present study was designed to test whether
      postconditioning has the same effect as preconditioning in promoting Cx43
      translocation to mitochondria and whether mitochondrial HSP90 modulates this
      effect. METHODS: Cellular models of hypoxic postconditioning (HPC) from rat heart
      derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of
      HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342
      fluorescent staining. Reactive oxidative species (ROS) production was assessed
      with the peroxide-sensitive fluorescent probe 2',7'-dichlorofluorescin in
      diacetate (DCFH-DA). The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and
      Cx43 protein levels were studied by Western blot analysis in total cell
      homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the
      HSP90 inhibitor geldanamycin (GA), ROS scavengers superoxide dismutase (SOD) and
      catalase (CAT), and small interfering RNA (siRNA) targeting Cx43 and HSP90 were
      also investigated. RESULTS: HPC significantly reduced hypoxia/reoxygenation (H/R)
      induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an
      increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and
      mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD
      plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC
      with either SOD or CAT did not. These data strongly supported the involvement of
      Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which
      plays a central role in HPC protection. Furthermore, HPC increased total and
      mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43;
      blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA) or
      siRNA targeting HSP90 prevented the protection of HPC and the HPC-induced
      association of Cx43, indicating that mitochondrial HSP90 was important for
      mitochondrial translocation of Cx43 during HPC. CONCLUSION: Mitochondrial HSP90
      played a central role in HPC cardioprotection, and its activity was linked to the
      mitochondrial targeting of Cx43, the activation of which triggered ROS signaling
      and the subsequent reduction of redox stress. Consequently, its target gene, Bcl
      2, was upregulated, and proapoptotic Bax was inhibited in the sarcolemma and
      mitochondria, ultimately attenuating H/R-induced cardiomyocyte apoptosis. These
      data reveal a novel mechanism of HPC protection.

PMID- 29179176
TI  - Neurons, Erythrocytes and Beyond -The Diverse Functions of Chorein.
AB  - Chorea-acanthocytosis (ChAc), a neurodegenerative disease, results from loss-of
      function-mutations of the chorein-encoding gene VPS13A. Affected patients suffer
      from a progressive movement disorder including chorea, parkinsonism, dystonia,
      tongue protrusion, dysarthria, dysphagia, tongue and lip biting, gait impairment,
      progressive distal muscle wasting, weakness, epileptic seizures, cognitive
      impairment, and behavioral changes. Those pathologies may be paralleled by
      erythrocyte acanthocytosis. Chorein supports activation of phosphoinositide-3
      kinase (PI3K)-p85-subunit with subsequent up-regulation of ras-related C3
      botulinum toxin substrate 1 (Rac1) activity, p21 protein-activated kinase 1
      (PAK1) phosphorylation, and activation of several tyrosine kinases. Chorein
      sensitive PI3K signaling further leads to stimulation of the serum and
      glucocorticoid inducible kinase SGK1, which in turn upregulates ORAI1, a Ca2+
      channel accomplishing store operated Ca2+-entry (SOCE). The signaling
      participates in the regulation of cytoskeletal architecture on the one side and
      cell survival on the other. Compromised cytoskeletal architecture has been shown
      in chorein deficient erythrocytes, fibroblasts and endothelial cells. Impaired
      degranulation was observed in chorein deficient PC12 cells and in platelets from
      ChAc patients. Similarly, decreased ORAI1 expression and SOCE as well as
      compromised cell survival were seen in fibroblasts and neurons isolated from ChAc
      patients. ORAI1 expression, SOCE and cell survival can be restored by lithium
      treatment, an effect disrupted by pharmacological inhibition of SGK1 or ORAI1.
      Chorein, SGK1, ORAI1 and SOCE further confer survival of tumor cells. In
      conclusion, much has been learned about the function of chorein and the molecular
      pathophysiology of chorea-acanthocytosis. Most importantly, a treatment halting
      or delaying the clinical course of this devastating disease may become available.
      A controlled clinical study is warranted, in order to explore whether the in
      vitro observations indeed reflect the in vivo pathology of the disease.

PMID- 29179177
TI  - Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with
      Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction.
AB  - BACKGROUND: The mismatch between traditional in vitro cell culture conditions and
      targeted chronic hypoxic myocardial tissue could potentially hamper the
      therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs). This
      study sought to address (i) the extent of change to BMSC biological
      characteristics in different in vitro culture conditions and (ii) the
      effectiveness of permanent hypoxic culture for cell therapy in treating chronic
      myocardial infarction (MI) in rats. METHODS: rat BMSCs were harvested and
      cultured in normoxic (21% O2, n=27) or hypoxic conditions (5% O2, n=27) until
      Passage 4 (P4). Cell growth tests, flow cytometry, and Bio-Plex assays were
      conducted to explore variations in the cell proliferation, phenotype, and
      cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in
      normoxia (n=6) or hypoxia (n=6) were intramyocardially injected into rat hearts
      that had previously experienced 1-month-old MI. The impact of cell therapy on
      cardiac segmental viability and hemodynamic performance was assessed 1 month
      later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography
      (PET) imaging and pressure-volume catheter, respectively. Additional
      histomorphological examinations were conducted to evaluate inflammation,
      fibrosis, and neovascularization. RESULTS: Hypoxic preconditioning significantly
      enhanced rat BMSC clonogenic potential and proliferation without altering the
      multipotency. Different profiles of inflammatory, fibrotic, and angiogenic
      cytokine secretion were also documented, with a marked correlation observed
      between in vitro and in vivo proangiogenic cytokine expression and tissue
      neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the
      myocardial viability of infarct segments and intrinsic contractility. CONCLUSION:
      Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and
      contractility, probably by modulating the inflammation and promoting
      angiogenesis.

PMID- 29179178
TI  - Serum Cystatin C Predicts AKI and the Prognosis of Patients in Coronary Care
      Unit: a Prospective, Observational Study.
AB  - BACKGROUND/AIMS: Acute Kidney Injury (AKI) is a serious clinical state associated
      with high morbidity and mortality, particularly in critical ill patients. We
      investigated the hypothesis that serum Cystatin C (sCysC) is a good predictor for
      AKI and may affect the short-term prognosis of coronary care unit (CCU) patients.
      METHODS: In this prospective, observational study, we screened 412 adults
      admitted to the CCU from January 1, 2014 to June 1, 2015 at Zhongnan Hospital of
      Wuhan University. Serum samples were obtained at the time of admission, and sCysC
      was quantified through nephelometry. AKI was defined based on KDIGO-AKI criteria.
      After the patients' hospital discharge, the survivors in this study were followed
      up for up to 2 years. The primary endpoint was the incidence of AKI stratified by
      severity stage, while the second endpoints included 2-year mortality,
      rehospitalization and failure in renal recovery rates, as well as the progression
      of AKI to CKD. RESULTS: According to the KDIGO-AKI criteria, AKI occurred in 130
      (31.6%) patients. After multivariate adjustments, the highest quartile of sCysC
      was associated with a 9-fold increased risk of incident AKI compared with the
      lowest quartile. For predicting AKI, sCysC [area under the receiver operating
      characteristic curve (AUC=0.842)] outperformed beta2-micro globulin (AUC=0.813)
      and the clinical model (AUC=0.777), and a cutoff of 1.255 mg/L yielded good
      sensitivity and specificity. After a median 19.8-month follow-up, 112 (27.2%)
      patients died within 2 years after admission. The sCysC independently predicted
      the risk of 2-year mortality [adjusted odds ratio (OR), 4.955; 95% confidence
      interval (95% CI), 2.853 to 8.603] and rehospitalization (OR, 3.128; 95% CI,
      2.011 to 4.867), as well as renal recovery failure (OR, 3.618, 95% CI, 1.753 to
      7.463). CONCLUSIONS: Serum CysC is a strong predictor of AKI and the short-term
      prognosis of CCU patients.

PMID- 29179179
TI  - Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells.
AB  - BACKGROUND/AIMS: Sputum symptoms are commonly seen in the elderly. This study
      aimed to identify an efficacious expectorant treatment stratagem through
      evaluating the secretion-promoting activation and cystic fibrosis transmembrane
      conductance regulator (CFTR) expression of the bioactive herbal monomer
      naringenin. METHODS: Vectorial Cl- transport was determined by measuring short
      circuit current (ISC) in rat airway epithelium. cAMP content was measured by
      ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in
      Calu-3 cells was determined by qPCR. RESULTS: Addition of naringenin to the
      basolateral side of the rat airway led to a concentration-dependent sustained
      increase in ISC. The current was suppressed when exposed to Cl--free solution or
      by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC
      increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by
      naringenin. Intracellular cAMP content was significantly increased by naringenin.
      With lipopolysaccharide stimulation, CFTR expression was significantly reduced,
      and naringenin dose-dependently enhanced CFTR mRNA expression. CONCLUSION: These
      results demonstrate that naringenin has the ability to stimulate Cl- secretion,
      which is mediated by CFTR through a signaling pathway by increasing cAMP content.
      Moreover, naringenin can increase CFTR expression when organism CFTR expression
      is seriously hampered. Our data suggest a potentially effective treatment
      strategy for sputum.

PMID- 29179180
TI  - Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio as Prognostic
      Predictors for Hepatocellular Carcinoma Patients with Various Treatments: a Meta
      Analysis and Systematic Review.
AB  - BACKGROUND/AIMS: Systemic inflammatory response (SIR) is widely considered as a
      preoperative risk factor for hepatocellular carcinoma (HCC) outcomes. The
      neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), two
      of the prognostic indices, have been investigated in post-therapeutic recurrence
      and survival of HCC. Here, we quantify the prognostic value of these two
      biomarkers and evaluate their consistency in different HCC therapies. METHODS: A
      systematic review of electronic database of the Web of Science, Embase, PubMed
      and the Cochrane Library was conducted to search for associations between the NLR
      and PLR in the blood and clinical outcomes of HCC. Overall survival (OS) and
      recurrence-free survival (RFS) were the primary outcomes, and hazard ratios (HRs)
      and 95% confidence intervals (95% CIs) were explored as effect measures. Subgroup
      analyses were performed to explore the heterogeneity of different therapies.
      RESULTS: A total of 24 articles comprising 6318 patients were included in the
      meta-analysis. Overall, the pooled outcomes revealed that a high NLR before
      treatment predicted a poor OS (HR: 1.54, 95% CI: 1.34 to 1.76, p<0.001) and poor
      RFS (HR: 1.45, 95% CI: 1.16 to 1.82, p=0.001). Moreover, an increased PLR
      predicted a poor OS (HR: 1.63, 95% CI: 1.34 to 1.98, p<0.001) and earlier HCC
      recurrence (HR: 1.52, 95% CI: 1.21 to 1.91, p<0.001). In addition, both the NLR
      and PLR were identified as independent risk factors for predicting OS and RFS in
      HCC patients in a subgroup analysis of different treatment types, including
      curative or palliative therapy; however, these results were not found in the
      sorafenib subgroup due to limited clinical research. CONCLUSION: An increased NLR
      or PLR indicated poor outcomes for patients with HCC. The NLR and PLR may be
      considered as reliable and inexpensive biomarkers for making clinical decisions
      regarding HCC treatment.

PMID- 29179181
TI  - Cysteine-Rich Intestinal Protein 1 Silencing Inhibits Migration and Invasion in
      Human Colorectal Cancer.
AB  - BACKGROUND/AIMS: Cysteine-rich intestinal protein 1 (CRIP1), a member of the
      LIM/double zinc finger protein family, is abnormally expressed in several tumour
      types. However, few data are available on the role of CRIP1 in cancer. In the
      present study, we aimed to investigate the expression profile and functions of
      CRIP1 in colorectal cancer. METHODS: To examine the protein expression level of
      CRIP1, immunohistochemistry (IHC) was performed on 56 pairs of colon cancer
      tissue samples. Western blotting was performed to investigate CRIP1 protein
      expression in four colon cancer cell lines. The endogenous expression of CRIP1
      was suppressed using short interfering RNAs (siRNAs). Cell proliferation assays
      were used to determine whether CRIP1 silencing affected cell proliferation. Flow
      cytometry analysis was used to detect cell apoptosis. The effects of silencing
      CRIP1 on cell migration and invasion was detected using the transwell and wound
      healing assays. RESULTS: IHC analysis showed that protein level of CRIP1 was
      significantly higher in tumour tissue samples than in paired non-tumour tissue
      samples and that the CRIP1 level was higher in metastatic tissue samples than in
      non-metastatic tissue samples. In addition, protein levels of CRIP1 were higher
      in highly metastatic colon cancer cell lines than in colon cancer cell lines with
      low metastasis. Further, CRIP1 silencing had no effect on cell proliferation or
      apoptosis in SW620 and HT29 cells. CRIP1 silencing suppressed cell migration and
      invasion obviously in SW620 and HT29 cells. CONCLUSION: The present study
      provides new evidence that abnormal expression of CRIP1 might be related to the
      degree of metastasis in colorectal cancer and that CRIP1 silencing could
      effectively inhibit migration and invasion during colorectal cancer development.
      These findings might aid the development of a biomarker for colon cancer
      prognosis and metastasis, and thus help to treat this common type of cancer.

PMID- 29179182
TI  - Therapeutic Effects of FK506 on IgA Nephropathy Rat.
AB  - BACKGROUND/AIMS: FK506 is an immunosuppressive drug and a calcineurin inhibitor
      that has been widely used in kidney disease in recent years. FK506 shows a wide
      range of biological and pharmaceutical effects; however, the mechanism of its
      anti- proliferative effect has not been well elucidated. An IgA nephropathy
      (IgAN) model was used to generate a mesangial cell proliferation model. This
      study aims to examine the effect of FK506 on IgAN rats and the underlying
      mechanisms. METHODS: Hematuria, proteinuria and renal function were measured. To
      observe the pathological conditions, we performed HE (hematoxylin - eosin) and
      PAS (periodic acid - schiff) staining. Transcription and protein expression
      levels were detected by qRT - PCR (quantitative real-time polymerase chain
      reaction) and Wb (western blotting). The location and semi-quantitative
      expression levels of TRPCs, CaN (Calcineurin) and alpha-SMA were examined by IHC
      (Immunohistochemical staining). RESULTS: We found that FK506 could improve
      hematuria, proteinuria and renal function, especially in the HF (high-dose FK506)
      groups. Renal pathological changes were ameliorated in the treatment groups.
      FK506 could significantly decrease TRPCs, CaN, phosphorylation of ERK1/2 and
      alpha-SMA expression. CONCLUSION: Taken together, these results suggest that the
      therapeutic effect of FK506 on IgAN might be partially associated with the down
      regulated expression of TRPC channels, CaN and phosphorylation of ERK1/2.

PMID- 29179183
TI  - Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer.
AB  - Long non-coding RNAs (lncRNAs), a class of non-coding transcripts, have recently
      been emerging with heterogeneous molecular actions, adding a new layer of
      complexity to gene-regulation networks in tumorigenesis. LncRNAs are considered
      important factors in several ovarian cancer histotypes, although few have been
      identified and characterized. Owing to their complexity and the lack of adapted
      molecular technology, the roles of most lncRNAs remain mysterious. Some lncRNAs
      have been reported to play functional roles in ovarian cancer and can be used as
      classifiers for personalized medicine. The intrinsic features of lncRNAs govern
      their various molecular mechanisms and provide a wide range of platforms to
      design different therapeutic strategies for treating cancer at a particular
      stage. Although we are only beginning to understand the functions of lncRNAs and
      their interactions with microRNAs (miRNAs) and proteins, the expanding literature
      indicates that lncRNA-miRNA interactions could be useful biomarkers and
      therapeutic targets for ovarian cancer. In this review, we discuss the genetic
      variants of lncRNAs, heterogeneous mechanisms of actions of lncRNAs in ovarian
      cancer tumorigenesis, and drug resistance. We also highlight the recent
      developments in using lncRNAs as potential prognostic and diagnostic biomarkers.
      Lastly, we discuss potential approaches for linking lncRNAs to future gene
      therapies, and highlight future directions in the field of ovarian cancer
      research.

PMID- 29179184
TI  - Potential Regulatory Effects of Corticotropin-Releasing Factor on Tight Junction
      Related Intestinal Epithelial Permeability are Partially Mediated by CK8
      Upregulation.
AB  - BACKGROUND/AIMS: Intestinal permeability and stress have been implicated in the
      pathophysiology of irritable bowel syndrome (IBS). Cytokeratin 8 (CK8), for the
      first time, has been shown to mediate corticotropin-releasing factor (CRF)
      induced changes in intestinal permeability in animal models of IBS. In this
      study, we investigated the regulatory effects of CRF on the permeability of human
      intestinal epithelial cells through the CK8-mediated tight junction. METHODS: The
      expression levels of corticotropin-releasing factor receptor 1 (CRFR1) and
      corticotropin-releasing factor receptor 2 (CRFR2) on the HT29 cell surface were
      determined by immunofluorescence, RT-PCR, and Western blotting. After treatment
      with 100 nM CRF for 72 h, the translocation of FITC-labelled dextran was measured
      in a transwell chamber; the structural changes of tight junctions were observed
      under transmission electron microscopy; the expression levels of CK8, F-actin and
      tight junction proteins ZO-1, claudin-1, and occludin were detected by
      immunoblotting and immunofluorescence. The activity of RhoA was detected by
      immunoprecipitation. Furthermore, the effects of CRF on intestinal epithelial
      permeability were examined in CK8-silenced HT29 cells, which were constructed by
      shRNA interference. RESULTS: CRF treatment increased FITC-labelled dextran
      permeability, caused the opening of tight junctions, induced increased
      fluorescence intensity of CK8 and decreased the intensities of ZO-1, claudin-1,
      and occludin, together with structural disruption. The expression levels of F
      actin, occludin, claudin-1, and ZO-1 were downregulated. RhoA activity peaked at
      30 min after CRF treatment. CRF-induced increased permeability, and
      downregulation of claudin-1 and occludin were not blocked by CK8 silencing.
      Nevertheless, CK8 silencing blocked the effects of CRF regarding the decrease in
      the expression levels of F-action and ZO-1 and increase in RhoA activity.
      CONCLUSION: CRF may increase intestinal epithelial permeability by upregulating
      CK8 expression, activating the RhoA signalling pathway, promoting intestinal
      epithelial actin remodelling, and decreasing the expression of the tight junction
      protein ZO-1. Other CK8-independent pathways may be involved in the
      downregulation of claudin-1 and occludin, which might also contribute to
      increased intestinal epithelial permeability.

PMID- 29179185
TI  - VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/beta
      Catenin Axis in Breast Cancer Cells.
AB  - BACKGROUND/AIMS: Targeting cancer stem cells (CSCs) is emerging as a promising
      method for cancer treatment. We previously indicated that knockdown of Neuropilin
      1(NRP-1) could inhibit breast cancer cell proliferation. Here, we continue
      exploring the roles and mechanisms of VEGF-A/NRP-1 axis in breast CSCs formation.
      METHODS: qRT-PCR was used to detect the levels of VEGF-A and NRP-1 in breast
      cancer sphere cells and wild-type cells. Mammospheres formation, flow cytometry,
      soft agar colony and tumor formation assays were performed to evaluate the
      effects of VEGF-A/NRP-1 on breast cancer stemness. Further HUVECs tube formation,
      cell invasion assays were carried out to detect the effects of VEGF-A/NRP-1 on
      breast cancer spheres-induced angiogenesis. Finally, Annexin V/PI apoptosis and
      CCK8 assays were used to detect the effects of VEGF-A/NRP-1 on chemoresistance.
      RESULTS: Overexpression of VEGF-A or NRP-1 conferred CSCs-related traits in MCF-7
      cells, while knockdown of VEGF-A or NRP-1 reduced CSCs-related traits in MDA-MB
      231 cells in vitro and in vivo. Notably, VEGF-A acted in a NRP-1 dependent way.
      Mechanistically, the VEGF-A/NRP-1 axis conferred CSCs phenotype via activating
      Wnt/beta-catenin pathway. CONCLUSION: our results suggest that VEGF-A/NRP-1 axis
      could confer CSCs-related traits and chemoresistance.

PMID- 29179186
TI  - FNAC: Sampling and Preparation Technique, Fixation, and Staining.

PMID- 29179187
TI  - Principles of Interpretation.

PMID- 29179188
TI  - Preliminaries.

PMID- 29179189
TI  - Normal Breast.

PMID- 29179190
TI  - Cytology of Inflammatory and Reactive Changes.

PMID- 29179191
TI  - Cystic Lesions.

PMID- 29179192
TI  - Epithelial Proliferative Lesions.

PMID- 29179193
TI  - Fibroepithelial Lesions.

PMID- 29179194
TI  - Invasive Carcinoma.

PMID- 29179195
TI  - Other Breast Neoplasms.

PMID- 29179196
TI  - Assessment of the Lymph Node Status.

PMID- 29179197
TI  - Ancillary Techniques.

PMID- 29179198
TI  - Concluding Remarks.

PMID- 29179200
TI  - Stress-Kinase Regulation of TASK-1 and TASK-3.
AB  - BACKGROUND/AIMS: TASK channels belong to the two-pore-domain potassium (K2P)
      channel family. TASK-1 is discussed to contribute to chronic atrial fibrillation
      (AFib) and has been together with uncoupling protein 1 found as a marker protein
      of brown adipose tissue (BAT) fat. In addition, TASK-1 was linked in a genome
      wide association study to an increased body mass index. A recent study showed
      that TASK-1 inhibition is causing obesity in mice by a BAT whitening and that
      these effects are linked to the mineralocorticoid receptor pathway, albeit the
      mechanism remained elusive. Therefore, we aimed to probe whether K2P channels are
      regulated by serum- and glucocorticoid-inducible kinases (SGKs) which are known
      to modify many cellular functions by modulating ion channels. METHODS: To this
      end we used functional co-expression studies and chemiluminescence-assays in
      Xenopus oocytes, together with fluorescence imaging and quantitative PCR
      experiments. RESULTS: SGKs and proteinkinase B (PKB) induced a strong, dose- and
      time-dependent current reduction of TASK-1 and TASK-3. SGK co-expression reduced
      the surface expression of TASK-1/3, leading to a predominant localization of the
      channels into late endosomes. The down regulation of TASK-3 channels was
      abrogated by the dynamin inhibitor dynasore, confirming a role of SGKs in TASK
      1/3 channel endocytosis. CONCLUSION: Stress-mediated changes in SGK expression
      pattern or activation is likely to alter TASK-1/3 expression at the surface
      membrane. The observed TASK-1 regulation might contribute to the pathogenesis of
      chronic AFib and provide a mechanistic link between increased mineralocorticoid
      levels and TASK-1 reduction, both linked to BAT whitening.

PMID- 29179201
TI  - Alteration of Tight Junction Protein Expression in Dahl Salt-Sensitive Rat
      Kidney.
AB  - BACKGROUND/AIMS: Altered pressure natriuresis is an important mechanism of
      hypertension, but it remains elusive at the molecular level. We hypothesized that
      in the kidney, tight junctions (TJs) may have a role in pressure natriuresis
      because paracellular NaCl transport affects interstitial hydrostatic pressure.
      METHODS: To assess the association of salt-sensitive hypertension with altered
      renal TJ protein expression, Dahl salt-sensitive (SS) and salt-resistant (SR)
      rats were put on an 8% NaCl-containing rodent diet for 4 weeks. Systolic blood
      pressure (SBP) and urine NaCl excretion were measured weekly, and kidneys were
      harvested for immunoblotting and quantitative PCR analysis at the end of the
      animal experiments. RESULTS: SBP was significantly higher in SS rats than in SR
      rats during the first to fourth weeks of the animal experiments. During the first
      and second week, urinary NaCl excretion was significantly lower in SS rats as
      compared with SR rats. However, the difference between the two groups vanished at
      the third and fourth weeks. In the kidney, claudin-4 protein and mRNA were
      significantly increased in SS rats as compared with SR rats. On the other hand,
      occludin protein and mRNA were significantly decreased in SS rats as compared
      with SR rats. The expression of claudin-2, claudin-7, and claudin-8 did not vary
      significantly between the two groups. CONCLUSIONS: In SS rats, SS hypertension
      was associated with differential changes in renal TJ protein expression. Both
      upregulation of claudin-4 and downregulation of occludin might increase
      paracellular NaCl transport in the kidney, resulting in impaired pressure
      natriuresis in SS rats.

PMID- 29179202
TI  - Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by
      Targeting MicroRNA-139.
AB  - BACKGROUND/AIMS: Acute myocardial infarction (AMI) occurs when blood supply to
      the heart is diminished (ischemia) for long time; ischemia is primarily caused
      due to hypoxia. The present study evaluated the effects of long non-coding RNA
      H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. METHODS: Hypoxic injury was
      confirmed by measuring cell viability, migration and invasion, and apoptosis
      using MTT, Transwell and flow cytometry assays, respectively. H19 expression
      after hypoxia was estimated by qRT-PCR. We then measured the effects of non
      physiologically expressed H19, knockdown of miR-139 with or without H19 silence,
      and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the
      interacted miRNA for H19 and downstream target gene were virtually screened and
      verified. The involved signaling pathways and the effects of abnormally expressed
      H19 on contractility of HL-1 cells were explored via Western blot analysis.
      RESULTS: Hypoxia induced decreases of cell viability, migration and invasion,
      increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased
      hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19
      knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was
      identified as a target of miR-139, and its expression was negatively regulated by
      miR-139. The mechanistic studies revealed that overexpression of Sox8 might
      decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and
      MAPK. Besides, H19 promoted contractility of HL-1 cells. CONCLUSION: These
      findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by
      miR-139-mediated up-regulation of Sox8, along with activation of the
      PI3K/AKT/mTOR pathway and MAPK.

PMID- 29179203
TI  - Maternal Hypercholesterolemia Associated with Nicotine Exposure in Adulthood May
      Induce Kidney Injury in Male Rats if Hypomagnesemia Occurs.
AB  - BACKGROUND/AIMS: Maternal hypercholesterolemia is a risk factor to renal injury
      in rat pups at adulthood, especially if they feed a cholesterol-enriched diet
      after weaning. However, the renal function of male pups of dams with
      hypercholesterolemia (PH) that were fed a regular chow from weaning to adulthood
      needs investigation, particularly those exposed to an adverse risk such as
      nicotine. METHODS: We evaluated the renal function of PH animals and we compared
      the data with those found in male pups of control dams (PC) at 3- and 6-month-old
      by inulin clearance. Moreover, we investigated the effect of nicotine treatment
      for 8 days in both PH and PC animals at 6 months old via metabolic function
      studies and by renal histological analysis. RESULTS: Inulin clearance and other
      renal function parameters were similar in PH and PC animals at 3 and 6 months
      old. Nevertheless, the PH group showed significant differences with regard to
      histological analysis despite a similar number of glomeruli. The glomerular area
      of PH animals was significantly smaller than that measured in PC animals, and the
      fractional interstitial area was significantly larger in PH animals than that
      measured in PC animals at 3 months old. With regard to nicotine treatment, we
      observed a trend for a reduction in creatinine clearance in both PC and PH
      groups, but only PH animals showed hypomagnesemia and the highest fractional
      interstitial area. CONCLUSIONS: The offspring exposed to a high cholesterol
      milieu during intrauterine and neonatal life may show a silent kidney injury at
      adulthood that may be aggravated by nicotine exposure if hypomagnesemia occurs.

PMID- 29179204
TI  - Clinical Significance of Myeloid Zinc Finger 1 Expression in the Progression of
      Gastric Tumourigenesis.
AB  - BACKGROUND/AIMS: To investigate the clinical significance of myeloid zinc finger
      1 (MZF1) expression in various gastric mucosal lesions including chronic
      superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal
      metaplasia (IM), dysplasia (DYS) and gastric cancer (GC) in comparison with
      normal tissues and gastric cell lines. METHODS: MZF1 protein expression was
      detected using immunohistochemical staining in 37 CSG, 88 CAG, 77 IM, 51 DYS, 165
      GC and 8 normal tissue samples. Quantitative real-time PCR (qRT-PCR) and western
      blotting were used to detect the level of MZF1 in gastric cell lines, 15 normal
      tissues and 34 GC samples, as well as 2 groups of paired primary GC and adjacent
      normal samples. RESULTS: Reduced MZF1 expression was detected in most GC cells
      and tissues. Among the gastric tissues consisting of various stages of lesions
      (normal, CSG, CAG, IM, DYS and GC), MZF1 protein expression was downregulated in
      precancerous lesions and GC. The data from clinical analyses showed that
      decreased MZF1 expression was correlated with tumour invasion (p = 0.044), lymph
      node metastasis (p = 0.048) and poor prognosis of GC patients (p = 0.003).
      Moreover, MZF1 was identified as an independent prognostic biomarker for GC
      patients in multivariate Cox regression analysis (p = 0.009). CONCLUSION:
      Downregulation of MZF1 was associated with gastric tumourigenesis, which may be a
      novel early predictive and prognostic biomarker in GC patients.

PMID- 29179205
TI  - Overexpression of TIMP3 Protects Against Cardiac Ischemia/Reperfusion Injury by
      Inhibiting Myocardial Apoptosis Through ROS/Mapks Pathway.
AB  - BACKGROUND/AIMS: Myocardial ischemia/reperfusion (I/R) injury remains a great
      challenge in clinical therapy. Tissue inhibitor of metalloproteinases 3 (TIMP3)
      plays a crucial role in heart physiological and pathophysiological processes.
      However, the effects of TIMP3 on I/R injury remain unknown. METHODS: C57BL/6 mice
      were infected with TIMP3 adenovirus by local delivery in myocardium followed by
      I/R operation or doxorubicin treatment. Neonatal rat cardiomyocytes were
      pretreated with TIMP3 adenovirus prior to anoxia/reoxygenation (A/R) treatment in
      vitro. Histology, echocardiography, in vivo phenotypical analysis, flow cytometry
      and western blotting were used to investigate the altered cardiac function and
      underlying mechanisms. RESULTS: The results showed that upregulation of TIMP3 in
      myocardium markedly inhibited myocardial infarct areas and the cardiac
      dysfunction induced by I/R or by doxorubicin treatment. TUNEL staining revealed
      that TIMP3 overexpression attenuated I/R-induced myocardial apoptosis,
      accompanied by decreased Bax/Bcl-2 ratio, Cleaved Caspase-3 and Cleaved Caspase-9
      expression. In vitro, A/R-induced cardiomyocyte apoptosis was abrogated by
      pharmacological inhibition of reactive oxygen species (ROS) production or MAPKs
      signaling. Attenuation of ROS production reversed A/R-induced MAPKs activation,
      whereas MAPKs inhibitors showed on effect on ROS production. Furthermore, in vivo
      or in vitro overexpression of TIMP3 significantly inhibited I/R- or A/R-induced
      ROS production and MAPKs activation. CONCLUSION: Our findings demonstrate that
      TIMP3 upregulation protects against cardiac I/R injury through inhibiting
      myocardial apoptosis. The mechanism may be related to inhibition of ROS-initiated
      MAPKs pathway. This study suggests that TIMP3 may be a potential therapeutic
      target for the treatment of I/R injury.

PMID- 29179206
TI  - Hybrid Complexes of High and Low Molecular Weight Hyaluronans Highly Enhance
      HASCs Differentiation: Implication for Facial Bioremodelling.
AB  - BACKGROUND/AIMS: Adipose-derived Stem Cells (ASCs) are used in Regenerative
      Medicine, including fat grafting, recovery from local tissue ischemia and scar
      remodeling. The aim of this study was to evaluate hyaluronan based gel effects on
      ASCs differentiation and proliferation. METHODS: Comparative analyses using high
      (H) and low (L) molecular weight hyaluronans (HA), hyaluronan hybrid cooperative
      complexes (HCCs), and high and medium cross-linked hyaluronan based dermal
      fillers were performed. Human ASCs were characterized by flow cytometry using
      CD90, CD34, CD105, CD29, CD31, CD45 and CD14 markers. Then, cells were treated
      for 7, 14 and 21 days with hyaluronans. Adipogenic differentiation was evaluated
      using Oil red-O staining and expression of leptin, PPAR-gamma, LPL and
      adiponectin using qRT-PCR. Adiponectin was analyzed by immunofluorescence, PPAR
      gamma and adiponectin were analyzed using western blotting. ELISA assays for
      adiponectin and leptin were performed. RESULTS: HCCs highly affected ASCs
      differentiation by up-regulating adipogenic genes and related proteins, that were
      also secreted in the culture medium. H-HA and L-HA induced a lower level of ASCs
      differentiation. CONCLUSION: HCCs-based formulations clearly enhance adipogenic
      differentiation and proliferation, when compared with linear HA and cross-linked
      hyaluronans. Injection of HCCs in subdermal fat compartment may recruit and
      differentiate stem cells in adipocytes, and considerably improving fat tissue
      renewal.

PMID- 29179207
TI  - Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and
      Stemness in Colorectal Cancer.
AB  - BACKGROUND/AIMS: Cancer stem cells (CSCs) are considered to be responsible for
      tumor relapse and metastasis, which serve as a potential therapeutic target for
      cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly
      in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its
      relevant mechanisms in colorectal cancer remain unclear. METHODS: CCK8 assay was
      employed to detect the cell viability. Sphere formation assay, colony formation
      assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC
      properties. Western blotting was performed to detect the expression of the
      stemness factors. Xenograft model was employed to identify the anti-cancer
      effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal
      Wallis test were used for the statistical comparisons. RESULTS: Aspirin
      attenuated colonosphere formation and decreased the ALDH1 positive cell
      population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth
      and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased
      the protein expression of stemness-related transcription factors, including c
      Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere
      formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed
      sphere formation, suggesting that NANOG is a key downstream target. Moreover, we
      found that aspirin repressed NANOG expression in protein level by decreasing its
      stability. CONCLUSION: We have provided new evidence that aspirin attenuates CSC
      properties through down-regulation of NANOG, suggesting aspirin as a promising
      therapeutic agent for colorectal cancer treatment.

PMID- 29179208
TI  - KLF 15 Works as an Early Anti-Fibrotic Transcriptional Regulator in Ang II
      Induced Renal Fibrosis via Down-Regulation of CTGF Expression.
AB  - BACKGROUND/AIMS: Angiotensin II (Ang II) has been regarded as an important
      profibrogenic cytokine in renal fibrosis. Kruppel-like factor 15 (KLF15) has been
      identified as an important negative transcription factor in renal fibrosis.
      However, little is known about the role of KLF15 in Ang II-induced renal
      fibrosis. METHODS: In this study, we randomized mice into a control group, Ang II
      group or Ang II plus losartan group. KLF15 expression was examined with real-time
      PCR and immunofluorescence in these groups. In vitro, KLF15 expression was
      examined by Western blot in rat renal fibroblasts (NRK-49F) stimulated with Ang
      II, and the effect of altered KLF15 expression on the regulation of the
      profibrotic factor connective tissue growth factor (CTGF) was further explored
      with co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP)
      analyses. RESULTS: Compared with the control group, the murine model of Ang II
      induced renal fibrosis demonstrated a significant decrease in renal KLF15
      expression at 4 weeks and presented with progressive renal fibrosis at 6 weeks.
      Meanwhile, losartan, an angiotensin type 1 (AT1) receptor antagonist, effectively
      prevented the down-regulation of KLF15 expression induced by Ang II infusion. In
      vitro, NRK-49F cells stimulated with Ang II exhibited a significant decrease in
      KLF15 expression, accompanied by a marked increase in the expression of
      profibrotic factors and in the production of extracellular matrix. The up
      regulation of CTGF expression induced by Ang II stimulation was inhibited by
      KLF15 overexpression in NRK-49F cells, and losartan treatment prevented the down
      regulation of KLF15 expression and the up-regulation of CTGF expression induced
      by Ang II stimulation. Furthermore, CoIP and ChIP assays revealed that the
      transcription regulator KLF15 directly bound to the co-activator P/CAF and
      repressed its recruitment to the CTGF promoter. CONCLUSIONS: Ang II down
      regulates KLF15 expression via the AT1 receptor, and KLF15 is likely to inhibit
      Ang II-induced CTGF expression by repressing the recruitment of the co-activator
      P/CAF to the CTGF promoter.

PMID- 29179209
TI  - Calycosin Suppresses Epithelial Derived Initiative Key Factors and Maintains
      Epithelial Barrier in Allergic Inflammation via TLR4 Mediated NF-kappaB Pathway.
AB  - BACKGROUND/AIMS: Calycosin is a bioactive component of Astragali Radix, a Chinese
      herb for treating allergy. We have previously demonstrated that calycosin
      effectively inhibited allergic inflammation efficiently. The aim of this study
      was to explore the mechanism of calycosin on epithelial cells in allergic
      inflammation. METHODS: An initial stage of atopic dermatitis (AD) model in which
      mice were just sensitized with FITC, was established in vivo and immortalized
      human keratinocytes (HaCaT cells) were utilized in vitro. Initiative key
      cytokines, TSLP and IL-33, were measured by ELISA, qPCR, immunofluorescence and
      Western blot. The junctions in epithelial cells were observed by electron
      microscopy and tight junctions (TJs) (Occludin and ZO-1) were assessed by Western
      blot and immunofluorescence. TLR4, MyD88, TAK1, TIRAP and NF-kappaB were measured
      by qPCR or Western blot. RESULTS: The results showed that TSLP and IL-33 were
      inhibited significantly by calycosin in the initial stage of AD model.
      Simultaneously, calycosin attenuated the separated gap among the epithelial cells
      and increased the expression of TJs. TSLP/IL-33 and TJs were similarly affected
      in LPS-stimulated HaCaT cells in vitro. Meanwhile, calycosin not only inhibited
      the expressions of TLR4, MyD88, TAK1 and TIRAP, but also reduced NF-kappaB
      activation in vitro and in vivo. An NF-kappaB inhibitor enhanced the expressions
      of TJs and reduced that of TSLP/IL-33 in LPS-stimulated HaCaT cells. CONCLUSION:
      These results indicated that calycosin reduced the secretion of TSLP/IL-33 and
      attenuated the disruption of epithelial TJs by inhibiting TLR4 mediated NF-kappaB
      signaling pathway. These findings help to understand the beneficial effects of
      calycosin on AD, and to develop effective preventive or therapeutic strategies to
      combat this disease and other epithelial barrier deletion-mediated allergic
      diseases.

PMID- 29179210
TI  - ENaCs as Both Effectors and Regulators of MiRNAs in Lung Epithelial Development
      and Regeneration.
AB  - Epithelial sodium channels (ENaC) play an important role in re-absorbing
      excessive luminal fluid by building up an osmotic Na+ gradient across the tight
      epithelium in the airway, the lung, the kidney, and the colon. The ENaC is a
      major pathway for retention of salt in kidney too. MicroRNAs (miRs), a group of
      non-coding RNAs that regulate gene expression at the post-transcriptional level,
      have emerged as a novel class of regulators for ENaC. Given the ENaC pathway is
      crucial for maintaining fluid homeostasis in the lung and the kidney and other
      cavities, we summarized the cross-talk between ENaC and miRs and recapitulated
      the underlying regulatory factors, including aldosterone, transforming growth
      factor-beta1, and vascular endothelial growth factor-A in the lung and other
      epithelial tissues/organs. We have compared the profiling of miRs between normal
      and injured mice and human lungs, which showed a significant alteration in
      numerous miRs in mouse models of LPS and ventilator induced ARDS. In addition, we
      reiterated the potential regulation of the ENaC by miRs in stem/ progenitor cell
      based re-epithelialization, and identified a promising pharmaceutic target of
      ENaC for removing edema fluid in ARDS by mesenchymal stem cells-released
      paracrine. In conclusion, it seems that the interactions between miRs and
      scnn1s/ENaCs are critical for lung development, epithelial cell turnover in adult
      lungs, and re-epithelialization for repair.

PMID- 29179211
TI  - Molecular Mechanism of MiR-136-5p Targeting NF-kappaB/A20 in the IL-17-Mediated
      Inflammatory Response after Spinal Cord Injury.
AB  - BACKGROUND/AIMS: The pathophysiology of spinal cord injury (SCI) results in
      serious damage to the human body via an increase in the secondary biological
      processes imposed by activated astrocytes. Abnormal expression of microRNAs after
      SCI has become a potential research focus. However, the underlying mechanisms are
      poorly understood. METHODS: SCI models were established in rats using Allen's
      method, and the BBB scoring method was employed to assess locomotor function.
      Lentivirus was used to infect rat astrocytes and SCI rats. Real-time PCR and
      antibody chip were used to measure gene expression and cytokine secretion.
      Western blot analysis was employed to detect protein expression. HE staining was
      used to assess the histological changes in SCI. The immunohistochemical staining
      of A20 and p-NF-kappaB in SCI was also analyzed. RESULTS: The in vitro experiment
      showed that miR-136-5p up-regulated the expression of p-NF-kappaB by down
      regulating the expression of A20 so that astrocytes produced inflammatory factors
      and chemokines. The in vivo experiment indicated that overexpressed miR-136-5p
      promoted the production of inflammatory factors, chemokines and p-NF-kappaB in
      SCI rats, whereas it inhibited the expression of A20 protein and increased
      inflammatory cell infiltration and injuries in the spinal cord. CONCLUSION: The
      current findings indicate that silencing miR-136-5p effectively decreased
      inflammatory factors and chemokines and protected the spinal cord via NF
      kappaB/A20 signaling in vivo and in vitro. In contrast, overexpression of miR-136
      5p had the opposite effect.

PMID- 29179212
TI  - LukS-PV-Regulated MicroRNA-125a-3p Promotes THP-1 Macrophages Differentiation and
      Apoptosis by Down-Regulating NF1 and Bcl-2.
AB  - BACKGROUND/AIMS: LukS-PV is a component of Panton-Valentine leukocidin (PVL). We
      have previously demonstrated that LukS-PV potently promoted differentiation and
      induced apoptosis in THP-1 cells. However, the precise mechanisms of these
      actions remain unknown. MicroRNAs (miRs) play important roles in cellular
      differentiation and apoptosis. This study aimed to investigate the role of miR
      125a-3p in LukS-PV-regulated differentiation and apoptosis and its underlying
      mechanism in THP-1 cells. METHODS: MicroRNA profiling analyses were conducted to
      determine differential miRNA expression levels in THP-1 cells treated with LukS
      PV. Cell differentiation and apoptosis were measured in THP-1 cells by gain-of
      function and loss-of-function experiments. Bioinformatics analysis and luciferase
      reporter assays were used to confirm the targets of miR-125a-3p. The effects of
      the miR-125a-3p targets on cellular differentiation were determined by knocking
      them down. RESULTS: MiR-125a-3p was up-regulated after treating the human
      monocytic leukaemia cell line THP-1 with LukS-PV. In addition, miR-125a-3p
      positively regulated apoptosis and differentiation in THP-1 cells treated with
      LukS-PV. Concordantly, luciferase reporter assays confirmed that
      neurofibromatosis type 1 (NF1) and B-cell lymphoma 2 (Bcl-2) were direct target
      genes of miR-125a-3p. Moreover, NF1 knockdown in THP-1 cells significantly
      promoted differentiation in vitro. Finally, the extracellular signal-regulated
      kinase (ERK) pathway, a downstream target of NF1, was activated after NF1
      knockdown. CONCLUSIONS: These findings confirm that miR-125a-3p is involved in
      LukS-PV-mediated cell differentiation and apoptosis in THP-1 cells.

PMID- 29179213
TI  - Melanotic Neuroectodermal Tumor of Infancy of the Upper Arm.
AB  - OBJECTIVE: To present a case of a 6-month-old infant with melanotic
      neuroectodermal tumor of infancy (MNTI) in the upper arm. CLINICAL PRESENTATION
      AND INTERVENTION: A 6-month-old female presented with a well-circumscribed lesion
      of the upper arm at the Children's Hospital Zagreb. A biopsy was performed and
      microscopy revealed 2 cell populations consisting of small neuroblastic cells and
      larger melanin-containing epithelial cells. An excisional biopsy performed 1
      month later confirmed the initial diagnosis of MNTI, but the tumor had increased
      in size since the initial biopsy. After complete surgical excision the patient
      recovered well with no recurrence. CONCLUSION: The MNTI located in the upper arm
      was diagnosed on first biopsy and surgically excised completely. The patient
      recovered without recurrence in a follow-up of 2.5 years.

PMID- 29179214
TI  - Cetuximab Enhanced the Cytotoxic Activity of Immune Cells during Treatment of
      Colorectal Cancer.
AB  - BACKGROUND/AIMS: Cetuximab is a chimeric IgG1 monoclonal antibody which targets
      the extracellular domain of epidermal growth factor receptor. This antibody is
      widely used for colorectal cancer (CRC) treatment but its influence on the immune
      system is incompletely understood. METHODS: The immune influence of cetuximab
      therapy in CRC patients was investigated by analyzing peripheral blood
      mononuclear cells using flow cytometry. We undertook in vitro cytotoxicity and
      cytokine-profile assays to ascertain the immunomodulatory effect of cetuximab
      treatment. RESULTS: The number of CD3+ T, CD8+ T, and natural killer (NK) cells
      was increased significantly and T-regulatory cells reduced gradually after
      cetuximab treatment. Percentage of CD4+ T, natural killer T (NKT)-like, invariant
      NKT, and dendritic cells was similar between baseline patients and cetuximab
      patients. Expression of CD137 on NK and CD8+ T cells was increased significantly
      after 4 weeks of cetuximab therapy. In vitro cetuximab treatment markedly
      increased expression of CD137 and CD107a on NK and CD8+ T cells. Cetuximab
      treatment promoted the cytotoxic activity of NK and CD8+ T cells against tumor
      cells. CONCLUSION: Cetuximab treatment promotes activation of the immune response
      but alleviates immunosuppression: this might be the underlying anti-CRC effect of
      cetuximab.

PMID- 29179215
TI  - Long Non-Coding RNA Linc-USP16 Functions As a Tumour Suppressor in Hepatocellular
      Carcinoma by Regulating PTEN Expression.
AB  - BACKGROUND/AIMS: Recent evidence has indicated the crucial regulatory roles of
      long non-coding RNAs (lncRNAs) in tumour biology. In hepatocellular carcinoma
      (HCC), aberrant expression of lncRNAs plays an essential role in HCC
      tumourigenesis. However, the potential roles and regulatory mechanisms of the
      novel human lncRNA, Linc-USP16, in HCC are unclear. METHODS: To investigate the
      function of Linc-USP16 in HCC, we first analysed the expression levels of Linc
      USP16 in HCC patient tissues and cell lines via q-RT-PCR and established
      overexpressed or knockdown HCC cell lines. RESULTS: Here, we found that Linc
      USP16 expression was significantly down-regulated in HCC patient tissues and cell
      lines. Further functional experiments suggested that Linc-USP16 could directly
      increase PTEN expression by acting as a competing endogenous RNA (ceRNA) for miR
      21 and miR-590-5p. These interactions led to repression of AKT pathway and
      inhibition of HCC cell proliferation and migration. CONCLUSION: Thus, our data
      showed that Linc-USP16, as a tumour suppressor, plays an important role in HCC
      pathogenesis and provides a new therapeutic strategy for HCC treatment.

PMID- 29179216
TI  - Heat Shock Protein 70 Negatively Regulates TGF-beta-Stimulated VEGF Synthesis via
      p38 MAP Kinase in Osteoblasts.
AB  - BACKGROUND/AIMS: We previously demonstrated that transforming growth factor-beta
      (TGF-beta) stimulates the synthesis of vascular endothelial growth factor (VEGF)
      through the activation of p38 mitogen-activated protein (MAP) kinase in
      osteoblast-like MC3T3-E1 cells. Heat shock protein70 (HSP70) is a ubiquitously
      expressed molecular chaperone. In the present study, we investigated the
      involvement of HSP70 in the TGF-beta-stimulated VEGF synthesis and the underlying
      mechanism in these cells. METHODS: Culture MC3T3-E1 cells were stimulated by TGF
      beta. Released VEGF was measured using an ELISA assay. VEGF mRNA level was
      quantified by RT-PCR. Phosphorylation of each protein kinase was analyzed by
      Western blotting. RESULTS: VER-155008 and YM-08, both of HSP70 inhibitors,
      significantly amplified the TGF-beta-stimulated VEGF release. In addition, the
      expression level of VEGF mRNA induced by TGF-beta was enhanced by VER-155008.
      These inhibitors markedly strengthened the TGF-beta-induced phosphorylation of
      p38 MAP kinase. The TGF-beta-induced phosphorylation of p38 MAP kinase was
      amplified in HSP70-knockdown cells. SB203580, an inhibitor of p38 MAP kinase,
      significantly suppressed the amplification by these inhibitors of the TGF-beta
      induced VEGF release. CONCLUSION: These results strongly suggest that HSP70 acts
      as a negative regulator in the TGF-beta-stimulated VEGF synthesis in osteoblasts,
      and that the inhibitory effect of HSP70 is exerted at a point upstream of p38 MAP
      kinase.

PMID- 29179217
TI  - Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through
      ERK1/2/NOX4 Signaling Pathway.
AB  - BACKGROUND/AIMS: Elevated production of reactive oxygen species (ROS) is linked
      to endothelial dysfunction and is one of the key contributors to the pathogenesis
      of diabetic vascular complications. Emerging evidence has indicated that ellagic
      acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological
      activities including radical scavenging. However, whether EA exerts a vasculo
      protective effect via antioxidant mechanisms in blood vessels exposed to diabetic
      conditions remains unknown. Accordingly, the goal of this current study was to
      determine whether EA decreases vascular ROS production and thus ameliorates
      endothelial dysfunction in the diabetic milieu. METHODS: Intact rat aortas and
      human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG)
      with and without EA co-treatment. Endothelium-dependent vasodilation was measured
      using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT
      PCR and western blotting, respectively. Oxidative stress was determined by
      measuring ROS levels using dihydroethidium (DHE) staining. RESULTS: Intact aortas
      exposed to HG condition displayed exacerbated ROS production and impairment of
      endothelium-dependent vasodilation, characterizing endothelial dysfunction. These
      effects were markedly reduced with EA treatment. HG enhanced ROS production in
      HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment
      blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4.
      CONCLUSIONS: EA significantly decreases endothelial ROS levels and ameliorates
      the impairment of vascular relaxation induced by HG. Our results suggest that EA
      exerts a vasculo-protective effect under diabetic conditions via an antioxidant
      effect that involves inhibition of ERK1/2 and downregulation of NOX4.

PMID- 29179218
TI  - Puerarin Enhances Ca2+ Reuptake and Ca2+ Content of Sarcoplasmic Reticulum in
      Murine Embryonic Stem Cell-Derived Cardiomyocytes via Upregulation of SERCA2a.
AB  - BACKGROUND/AIMS: The embryonic stem cell-derived cardiomyocytes (ES-CMs) serve as
      potential sources for cardiac regenerative therapy. However, the immature
      sarcoplasmic reticulum (SR) function of ES-CMs prevents its application. In this
      report, we examined the effect of puerarin, an isoflavone compound, on SR
      function of murine ES-CMs. METHODS: Murine ES-CMs were harvested by embryoid body
      based differentiation method. Confocal calcium imaging and whole-cell patch
      clamps were performed to assess the function of SR. The mRNA expression levels of
      SR-related genes were examined by quantitative PCR. The protein expression of
      sarcoplasmic reticulum calcium-ATPase 2a (SERCA2a) was evaluated by
      immunofluorescent and western blot. RESULTS: Long-term application of puerarin
      promotes basic properties of spontaneous calcium transient with increased
      amplitude, decay velocity, and decreased duration. Puerarin fails to alter ICa,L
      but increases the Ca2+ content of SR. Puerarin-treated ES-CMs have intact SR Ca2+
      cycling with more SR Ca2+ reuptake. Long-term application of puerarin
      asynchronously upregulates the mRNA and protein expression of SERCA2a, as well as
      the transcripts of calsequestrin and triadin in developing ES-CMs. Application of
      puerarin during the stage of post-cardiac differentiation upregulates dose
      dependently the transcripts of SERCA2a, phospholamban and tridin which can be
      reversed by the inhibitors of the PI3K/Akt and MAPK/ERK signaling pathways, but
      shows no effect on the protein expression of SERCA2a. CONCLUSION: This study
      demonstrates that long-term puerarin treatment enhances Ca2+ reuptake and Ca2+
      content via upregulation of SERCA2a.

PMID- 29179220
TI  - [Vitreous Surgery for Macular Retinoschisis in a Highly Myopic Eye].

PMID- 29179219
TI  - A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts
      Acute Renal Allograft Rejection.
AB  - BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal
      transplantation, with no widely-accepted non-invasive biomarker. This study aimed
      to explore the expression profiles of long non-coding RNAs (lncRNAs) in the
      peripheral blood (PB) of renal transplant recipients and their potential
      diagnostic values. METHODS: The genome-wide lncRNA expression profiles were
      analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and
      ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was
      determined using receiver operator characteristic curve, with area under the
      curve (AUC) and 95% confidential interval (CI). Finally, a risk score was
      constructed with logistical regression model. RESULTS: A total of 162 lncRNAs
      were found differentially expressed in PRTx cohort, while 163 in ARTx cohort.
      Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and
      could distinguish AR recipients from those without AR. Finally, a risk score with
      two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited
      excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and
      ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature
      of two lncRNAs in PB could serve as a novel non-invasive biomarker for the
      diagnosis of AR in both pediatric and adult renal transplant recipients.

PMID- 29179221
TI  - [Vitreomacular Traction Following Anti-VEGF Therapy - Two Cases].
AB  - Vitreomacular traction syndrome (VMTS) is defined as an incomplete or anomalous
      posterior vitreous detachment resulting in tractional forces at the macular
      region. In the context of anti-VEGF therapy, the formation of vitreoretinal
      traction has mainly been reported as a potential complication of VEGF inhibition
      in ischemic proliferative retinal disease, such as proliferative diabetic
      retinopathy. In this report, we present two patients who developed VMTS during
      anti-VEGF therapy for exudative age-related macular degeneration and diabetic
      macular edema. VMTS following anti-VEGF therapy of exudative macular diseases is
      rare. The exact pathomechanism remains unclear. However, there is a hypothesis
      that in eyes with adherent vitreous cortex, the induction of fibrosis as a result
      of the VEGF inhibition may lead to vitreomacular traction.

PMID- 29179222
TI  - Gap-Balancing versus Measured Resection Technique in Total Knee Arthroplasty: A
      Comparison Study.
AB  - Proper femoral component alignment in the axial plane during total knee
      arthroplasty (TKA) depends on accurate bone cuts and soft tissue balancing. Two
      methods that are used to achieve this are "measured resection" and "gap
      balancing." However, a controversy exists as to which method is more accurate and
      leads to better outcomes. Therefore, the purpose of this study was to evaluate:
      (1) implant survivorship, (2) patient outcomes, (3) complications, and (4)
      radiographic analysis comparing patients who underwent TKA with either gap
      balancing or measured resection techniques. A total of 214 consecutive patients
      (221 knees) underwent primary TKA by a single surgeon between 2011 and 2012.
      Component alignment was achieved by using measured resection in 116 knees and gap
      balancing was used in 105 knees. The patients had a mean age of 66 years (range,
      44-86 years) and a mean body mass index of 32 kg/m2 (range, 22-52 kg/m2). Patient
      range-of-motion (ROM) and Knee Society (KS) function and pain scores, and
      radiographic assessment, were assessed preoperatively and postoperatively at ~6
      weeks, 3 months, 1 year, and then annually. The mean follow-up time was 3 years.
      A Kaplan-Meier's analysis was performed to calculate the survivorship. The
      aseptic survivorship was 98% in both the measured resection and gap-balancing
      groups. The mean ROM was not significantly different between the measured
      resection and gap-balancing groups (123 vs. 123 degrees, p = 0.990). There were
      no significant differences between the two groups in terms of the KS function
      scores (86 vs. 85 points, p = 0.829) or the KS pain scores (93 vs. 92 points, p =
      0.425). Otherwise, the radiographic evaluation at latest follow-up did not
      demonstrate any evidence of progressive radiolucencies or loosening, of any
      prosthesis. The results of this study found that at a mean follow-up of 3 years,
      both the measured resection and gap-balancing techniques achieved excellent
      survivorship and postoperative outcomes. This demonstrates that both methods can
      be used to achieve accurate femoral component alignment with similar short-term
      outcomes.

PMID- 29179223
TI  - Coronal Correction for Severe Deformity Using Robotic-Assisted Total Knee
      Arthroplasty.
AB  - Although robotic-assisted total knee arthroplasty (TKA) has the potential to
      accurately reproduce neutral alignment, it is still unclear if this correction is
      attainable in patients who have severe varus or valgus deformities. Therefore,
      the purpose of this study was to assess a single surgeon's experience with
      correcting coronal deformities using the robotic-assisted TKA device.
      Specifically, we looked at correction of varying degrees of varus and valgus
      deformity in patients who underwent robotic arm-assisted TKA. A total of 330
      robotic-assisted TKA cases performed by a single surgeon were analyzed.
      Preoperative CT scans were registered to the robotic-assisted software to create
      a three-dimensional rendering from which coronal alignment was measured.
      Postoperative coronal alignment measurements were taken in the operating room
      using the robotic-assisted device after trial component placement. The robotic
      assisted device uses optical tracking from navigation probes placed on the distal
      femur and proximal tibia. The robotic-assisted software can register these probes
      as bony landmarks to measure coronal alignment in the distal plane of the femoral
      component and proximal plane of the tibial component. A total of 261 cases were
      of varus knees, 46 cases were of valgus knees, and 23 cases had 0 degrees 
      preoperative alignment. Severe deformity was defined as 7 degrees  or greater
      deformity. Preoperative neutral alignment was defined as 0 degrees , while
      postoperative neutral alignment was defined as 0 degrees  +/- 3 degrees . There
      were 129 patients with and initial severe varus and 7 patients with an initial
      severe valgus deformity of 7 degrees  or greater. Patients were divided into
      varus or valgus cohorts, and analysis was performed on the overall cohort, as
      well as nonsevere (<7 degrees ) and severe (7 degrees  or greater) deformity
      cohorts.All 132 knees with initial varus deformity of less than 7 degrees  were
      corrected to neutral (mean 1 degrees , range -1-3 degrees ). A total of 82 knees
      (64%) with 7 degrees  or greater varus deformity were corrected to neutral (mean
      2 degrees , range 0-3 degrees ). However, roughly 30% of patients with severe
      deformity who were not corrected to neutral were still corrected within a couple
      of degrees of neutral. There were seven knees with 7 degrees  or greater valgus
      deformity, and all were corrected to neutral (mean 2 degrees , range 0-3 degrees
      ). This study demonstrated that all knees were corrected in the appropriate
      direction within a few degrees of neutral, and no knees were overcorrected. The
      implication of this ability to achieve alignment goals on clinical outcomes will
      need to be evaluated in future studies. The results from this study demonstrate
      the potential for the robotic-assisted device during TKA in helping surgeons
      achieve a preoperatively planned desired neutral alignment.

PMID- 29179224
TI  - Evaluation of the Implantable Doppler Probe for Free Flap Monitoring in Lower
      Limb Reconstruction.
AB  - BACKGROUND:  Timely reexploration and reanastomoses can salvage failing free
      flaps. The use of the implantable Doppler probe provides direct evidence of
      vascular impairment of the microvascular anastomoses and allows for postoperative
      NPWT. The aim of this retrospective study was to compare the Doppler probe to
      conventional monitoring techniques for free flap monitoring in lower limb
      reconstruction and to identify risk factors for perfusion disturbance and
      reexploration. METHODS:  All patients receiving free muscle flap reconstruction
      for lower limb soft tissue defects at our department from 2000 to 2013 were
      included, and all adverse events, timely detection of perfusion problems, and
      outcome of revision surgery were assessed by chart analysis. RESULTS:  For lower
      limb reconstruction, 110 free muscle transfers were performed of which 41 muscle
      flaps were conventionally monitored and 69 flaps were monitored using the
      implantable Doppler probe. In 18 cases, the free muscle flaps needed revision
      because of perfusion disturbances. The salvage rate was 80% with monitoring by
      the implantable Doppler probe compared with 62.5% using conventional monitoring
      methods resulting in success rates of 95.7 and 92.7%, respectively. CONCLUSION: 
      The use of the implantable Cook-Swartz Doppler probe represents a safe monitoring
      method for lower limb reconstruction, which allows for the additional use of
      NPWT. Higher salvage and revision success rates can be attributed to an earlier
      detection of perfusion impairment. However, a larger patient cohort is necessary
      to verify superiority over conventional postoperative monitoring.

PMID- 29179225
TI  - Staged Reconstruction (Delayed-Immediate) of the Maxillectomy Defect Using
      CAD/CAM Technology.
AB  - BACKGROUND:  Computer-aided design/computer-aided manufacturing (CAD/CAM)
      technology has become increasingly popular for free fibula reconstruction of the
      mandible. The same technology, however, has not been widely utilized in immediate
      complex midface reconstruction utilizing free fibula flaps. Maxillary defects are
      difficult to precisely predict or produce matched cutting guides for after the
      ablative surgery. We present a protocol for "delayed-immediate" two-stage
      reconstruction for complex mid-facial defects, by delaying lymph node neck
      dissection and using CAD/CAM technology for delayed bony reconstruction. METHODS:
      Stage 1 includes the extirpative surgery, placement of a temporary obturator,
      and an immediate post-excision fine cut computed tomography (CT) of the defect
      that is used for CAD/CAM planning. The time interval between stages is used for
      virtual surgical planning (VSP) and provides an opportunity for the final
      pathologic margins to be evaluated. At stage 2, definitive reconstruction is
      performed in conjunction with the delayed neck dissection. Briefly delaying the
      neck dissection until stage 2 allows for recipient vessel dissection and
      microsurgical anastomoses to safely occur in a surgically naive neck. CONCLUSION:
      A two-stage delayed-immediate reconstruction of complex mid-face defects can be
      safely and effectively performed. This protocol takes advantage of advancing
      CAD/CAM technology, provides an opportunity to evaluate final margins, and avoids
      recipient vessel dissection and microsurgery in previously operated or irradiated
      necks.

PMID- 29179226
TI  - Leptin and its Relation to Autonomic Activity, Endothelial Cell Activation and
      Blood Pressure in a Young Black and White Population: The African-PREDICT study.
AB  - An increasing prevalence of obesity-related hypertension is observed in the youth
      and may have severe consequences for future cardiovascular disease development.
      Previous studies portrayed leptin as a potential factor involved in obesity
      related hypertension development. In order to understand leptin's contributions
      to early cardiovascular deterioration, we investigated leptin and its
      associations with measures of autonomic activity, endothelial activation, and
      blood pressure in young healthy black and white men and women. We included 820
      participants (aged 20-30 years) and determined serum leptin and endothelial
      cellular adhesion molecules. We measured 24-h blood pressure, heart rate, and
      heart rate variability components. In multivariate-adjusted regression analyses,
      we found consistent associations between markers of autonomic activity (such as
      24-h heart rate, day and night-time heart rate as well as heart rate variability
      total power) and leptin in both white (all p<=0.001) and black men (all
      p<=0.040). These findings were absent or less prominent in women, despite their
      almost 10-fold higher leptin levels than men. Only in white men, 24-h diastolic
      blood pressure was associated with leptin (Std beta=0.37; p=0.006). This
      association was found to be partly mediated by autonomic activity (24-h heart
      rate variability total power). No independent associations were observed between
      leptin and markers of endothelial cell activation, irrespective of race or
      gender. Leptin's independent association with autonomic neural activity in a
      young apparently healthy population suggests an early influence of leptin on
      autonomic function and future blood pressure elevation especially in men.

PMID- 29179227
TI  - [On the risk of dependence on gabapentinoids].
AB  - In the last ten years, the prescriptions of the gabapentinoids gabapentin and
      pregabalin increased largely also in Germany. Since several national and
      international pharmacovigilance-databases have warned for abuse liabilities and
      overdose fatalities in association with both gabapentinoids, which moreover,
      became to be sold on internet and black-markets, their addictive power has been
      subject to an ongoing clinical debate. As pre- and post-approval clinical trials
      did not reveal significant signs of dependence on gabapentin or pregabalin, we
      systematically searched in PubMed and Scopus for clinical studies and case
      reports being associated with abuse of and dependence on these drugs. We found 14
      clinical-epidemiologic studies and 38 case reports/series. These were evaluated
      for i) fulfilled dependence criteria according to ICD-10, ii) non-medical self
      administration and their duration, iii) relapses, iv) social sequels, and v)
      cases seeking treatment for misusing gabapentin or pregabalin. Mostly, the cases
      of abuse of and dependence on gabapentinoids appeared to be associated with other
      substance dependencies, primarily opiate dependence and polyvalent drug use. Drug
      users preferred pregabalin citing a faster and stronger euphoria ("liking") than
      achievable with oral gabapentin. Both gabapentinoids were anxiolytic in
      therapeutic doses, stimulating in lower and sedating along with increasing doses.
      Fatalities have been described mainly in the population of opiate dependents and
      polyvalent drug users, predominantly together with excessive pregabalin
      overdosing. It is debated whether the gabapentinoids were indeed the main cause
      of death in these cases or whether gabapentin and pregabalin had been only
      bystanders. Tolerance and withdrawal symptoms (physical dependence) of
      gabapentinoids appeared to be common in medical and non-medical use of
      gabapentinoids. There were only 4 persons who had fulfilled behavioral dependence
      criteria of gabapentinoids (all had used pregabalin) and had no association with
      other substance use disorders (apart from nicotine). Regarding the transitions
      from prescription to non-medical self-administration, the frequency and duration
      of self-administrations as well as the number of reported relapses, pregabalin
      appeared also to be more addictive than gabapentin. However, all these events
      were reported rather infrequently compared with traditional substances of abuse.
      We did not find a case with social sequalea due to the use of gabapentinoids or a
      person who sought treatment for his gabapentin or pregabalin use. Therefore, the
      gabapentinoids were assumed to possess a lower "wanting" in consideration of
      Berridge's and Robinsons's incentive-sensitization theory of addiction. Also,
      anti-adverse selection of gabapentinoids is discussed to be present in the
      population of opioid and multi-drug users. Based upon all these results and
      assumptions, we have estimated the relative risk of dependence on gabapentinoids
      by using an algorithm which was previously developed by Griffith and Johnson for
      evaluation of the abuse liabilities of sedatives. Overall, the risk of harm and
      dependence on gabapentinoids appeared to be lower than that of other sedatives
      (and stimulants). In addition, pregabalin appeared to be somewhat riskier than
      gabapentin. We think that in patients with current or past substance use
      disorders, the treatment with gabapentinoids should be avoided or if
      indispensable, these drugs should be administered exclusively over a limited time
      span with caution by using a therapeutic and prescription monitoring.

PMID- 29179228
TI  - Can We Rely on AGNP Therapeutic Targets Also For LAI Antipsychotics?
AB  - The updated AGNP Consensus Guidelines for Therapeutic Drug Monitoring (TDM) in
      Neuropsychopharmacology recently published in the journal have reinforced the key
      role of TDM to individualize psychoparmacological therapies in clinical practice.
      However, we believe, that these guidelines have missed the important opportunity
      to face with, and to provide useful information on, the emerging issue of long
      acting injectable formulations of atypical antipsychotics. Specific therapeutic
      ranges also for these formulations should be included in the next AGNP
      guidelines.

PMID- 29179229
TI  - Learning curve and competence for volumetric laser endomicroscopy in Barrett's
      esophagus using cumulative sum analysis.
AB  - BACKGROUND AND STUDY AIMS:  Little is known about the learning curve for image
      interpretation in volumetric laser endomicroscopy (VLE) in Barrett's esophagus
      (BE). The goal of this study was to calculate the learning curve, competence of
      image interpretation, sensitivity, specificity, and accuracy of VLE among novice
      users. METHODS:  31 novice users viewed 96 VLE images electronically at three
      academic institutions after a brief training session. There were 24 images of
      each histologic type: normal gastric cardia, normal esophageal squamous
      epithelium, non-neoplastic BE, and neoplastic BE. The users were asked to
      identify the correct tissue type and level of confidence. The cumulative
      summation (CUSUM) technique was used to construct a learning curve. RESULTS:  22
      (71 %) of the physicians achieved VLE interpretation competency during their 96
      slide review. Half of the physicians achieved competency at 65 images (95 %
      confidence interval [CI] 45 - 85). There was a statistically significant
      association between confidence in diagnosis and selecting the correct histologic
      tissue type (P < 0.001). The median accuracy for esophageal squamous epithelium,
      normal gastric cardia, non-neoplastic BE, and neoplastic BE was 96 % (95 %CI 95 %
      - 96 %), 95 % (95 %CI 94 % - 96 %), 90 % (95 %CI 88 % - 91 %), 96 % (95 %CI 95 % 
      96 %). The overall accuracy was 95 % (95 %CI 93 % - 95 %). CONCLUSION: The
      majority of novice users achieved competence in image interpretation of VLE for
      BE, using a pre-selected image set, with a favorable learning curve after a brief
      training session. An electronic review of VLE images, prior to real-time use of
      VLE, is encouraged.

PMID- 29179230
TI  - Endoscopic subtypes of colorectal laterally spreading tumors (LSTs) and the risk
      of submucosal invasion: a meta-analysis.
AB  - BACKGROUND AND STUDY AIMS: Many studies have reported on laterally spreading
      tumors (LSTs), but systematic reviews of the data to determine their risk of
      containing submucosal invasion (SMI) are lacking. We systematically screened and
      analyzed the available literature to provide a more solid basis for evidence
      based treatment. METHODS: We conducted a systematic search in PubMed, Embase, the
      Cochrane Library, and Scopus for published articles until July 2017. We estimated
      pooled prevalence or odds ratios (ORs) with 95 % confidence intervals (CIs),
      using random-effects models. We classified endoscopic subtypes into granular LST,
      which comprises the homogeneous and nodular mixed subtypes, and non-granular LST,
      which comprises the flat elevated and pseudodepressed subtypes. RESULTS: We
      identified 2949 studies, of which 48 were included. Overall, 8.5 % (95 %CI 6.5 % 
      10.5 %) of LSTs contained SMI. The risk of SMI differed among the LST subtypes:
      31.6 % in non-granular pseudodepressed LSTs (95 %CI 19.8 % - 43.4 %), 10.5 % in
      granular nodular mixed LSTs (95 %CI 5.9 % - 15.1 %), 4.9 % in non-granular flat
      elevated LSTs (95 %CI 2.1 % - 7.8 %), and 0.5 % in granular homogenous LSTs (95
      %CI 0.1 % - 1.0 %). SMI was more common in distally rather than in proximally
      located LSTs (OR 2.50, 95 %CI 1.24 - 5.02). The proportion of SMI increased with
      lesion size (10 - 19 mm, 4.6 %; 20 - 29 mm, 9.2 %; >= 30 mm, 16.5 %). The pooled
      prevalence of patients with one or more LSTs in the general colonoscopy
      population was 0.8 % (95 %CI 0.6 % - 1.1 %). CONCLUSION: The majority of LSTs are
      non-invasive at the time of colonoscopic detection and can be treated with
      (piecemeal) endoscopic mucosal resection. Pretreatment diagnosis of endoscopic
      subtype, specifying areas of concern (nodule or depression), determines those
      LSTs at highest risk of containing SMI, where en bloc resection is the preferred
      therapy.

PMID- 29179231
TI  - 4H Leukodystrophy: Lessons from 3T Imaging.
AB  - 4H leukodystrophy is characterized by hypomyelination, hypodontia, and
      hypogonadotropic hypogonadism. With its variability in clinical symptoms,
      application of pattern recognition to identify specific magnetic resonance
      imaging (MRI) features proved useful for the diagnosis. We collected 3T MR
      imaging data of 12 patients with mutations in POLR3A (n = 8), POLR3B (n = 3), and
      POLR1C (n = 1), all obtained at the same scanner. We assessed these images and
      compared them with previously obtained 1.5T images in 8 patients. Novel MRI
      findings were myelin islets, closed eye sign, and a cyst-like lesion in the
      splenium. Myelin islets were variable numbers of small T1 hyperintense and T2
      hypointense dots, mostly in the frontal and parietal white matter, and present in
      all patients. This interpretation was supported with perivascular staining of
      myelin protein in the hypomyelinated white matter of a deceased 4H patient. All
      patients had better myelination of the medial lemniscus with a relatively
      hypointense signal of this structure on axial T2-weighted (T2W) images ("closed
      eye sign"). Five patients had a small cyst-like lesion in the splenium. In 10
      patients with sagittal T2W images, we also found spinal cord hypomyelination. In
      conclusion, imaging at 3T identified additional features in 4H leukodystrophy,
      aiding the MRI diagnosis of this entity.

PMID- 29179232
TI  - Differentially Regulated Cell-Free MicroRNAs in the Plasma of Friedreich's Ataxia
      Patients and Their Association with Disease Pathology.
AB  - Friedreich's ataxia (FRDA) is a multisystem disease affecting the predominately
      nervous system, followed by muscle, heart, and pancreas. Current research focused
      on therapeutic interventions aimed at molecular amelioration, but there are no
      reliable noninvasive signatures available to understand disease pathogenesis. The
      present study investigates the alterations of plasma cell-free microRNAs (miRNAs)
      in FRDA patients and attempts to find the significance in relevance with the
      pathogenesis. Total RNA from the plasma of patients and healthy controls were
      subjected to miRNA microarray analysis using Agilent Technologies microarray
      platform. Differentially regulated miRNAs were validated by SYBR-green real-time
      polymerase chain reaction (Thermo Fisher Scientific). The study identified 20
      deregulated miRNAs (false discovery rate < 0.01, fold change >= 2.0 <=) in
      comparison with healthy controls; out of which 17 miRNAs were upregulated, and 3
      miRNAs were downregulated. Target and pathway analysis of these miRNAs have shown
      association with neurodegenerative and other clinical features in FRDA. Further
      validation (n = 21) identified a set of significant (p < 0.05) deregulated
      miRNAs; hsa-miR-15a-5p, hsa-miR-26a-5p, hsa-miR-29a-3p, hsa-miR-223-3p, hsa-24
      3p, and hsa-miR-21-5p in comparison with healthy controls. These miRNAs were
      reported to influence various pathological features associated with FRDA. The
      present study is expected to aid in the understanding of disease pathogenesis.

PMID- 29179233
TI  - A Systematic Review of the Efficacy of Levetiracetam in Neonatal Seizures.
AB  - OBJECTIVE: Seizures are the most common neurological complication in neonatal
      intensive care units. Phenobarbital (PB) remains the first-line antiepileptic
      drug (AED) for neonatal seizures despite known neurotoxicity. Levetiracetam (LEV)
      is a newer AED not approved for neonates. Retrospective and pilot studies have
      investigated the use of LEV in neonatal seizures. Our objective was to compare
      the efficacy of LEV to PB in neonatal seizures based upon published data.
      METHODS: We searched PubMed to perform a systematic review. We found no studies
      of LEV with comparison or control groups; therefore, we utilized data from two
      randomized controlled trials of PB as our comparison group. RESULTS: Five studies
      of LEV met all inclusion/exclusion criteria. The pooled sample size for LEV was
      102 (48 received primary LEV, 54 received secondary LEV). The pooled sample size
      for primary PB was 52. Complete or near-complete seizure cessation was achieved
      as follows: primary LEV 37/48 (77%), secondary LEV 34/54 (63%), and primary PB
      24/52 (46%). CONCLUSION: Our findings suggest that LEV may be at least as or more
      effective for neonatal seizures as PB. Our review, though limited, is the first
      to examine LEV efficacy compared with PB in neonates.

PMID- 29179234
TI  - Mild Encephalitis/Encephalopathy with Reversible Splenial Lesion (MERS) due to
      Cytomegalovirus: Case Report and Review of the Literature.
AB  - Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico
      radiological syndrome characterized by a transient mild encephalopathy and MRI
      findings of a reversible lesion in the splenium of corpus callosum (SCC). It is
      classified in MERS type I and MERS type II, depending on the involvement of SCC
      alone or also other white matter areas. The syndrome mainly affects children and
      young adults; the prognosis is favorable with complete or nearly complete
      neurological and radiological resolution within days or weeks. The vast majority
      of the cases described in the literature involve Asian and Australian children.
      The exact pathophysiology is unknown; however, infectious-related MERS (in
      particular virus associated MERS) remains the most common cause of reversible
      splenial lesions in childhood. To the best of our knowledge, there is only one
      published case of MERS associated with cytomegalovirus (CMV) infection involving
      an Australian child. We present here the first case of a CMV-related MERS in a
      European Caucasian child.

PMID- 29179235
TI  - Atypical Neurologic Phenotype and Novel SLC30A10 Mutation in Two Brothers with
      Hereditary Hypermanganesemia.
AB  - Manganese (Mn) is an essential element in trace quantity but large amounts are
      toxic. A novel hereditary disorder encompassing high blood Mn levels, dystonia,
      polycythemia, distinctive T1 hyperintense signals in the basal ganglia on
      magnetic resonance imaging (MRI) brain, and chronic liver disease was recently
      described. The disorder is caused by mutations in a Mn transporter encoding gene
      SLC30A10. We are reporting the clinical features of this rare disorder in two
      Saudi brothers. The older brother presented with progressive gait difficulties,
      hypotonia, intermittent dystonia, polycythemia, and characteristic T1
      hyperintense lesions on MRI brain. SLC30A10 sequencing identified a novel
      missense mutation. The younger brother was identified in presymptomatic phase on
      family screening. Chelation therapy with disodium calcium edetate
      (ethylenediaminetetraacetic acid, EDTA) led to stabilization of gait, reduction
      in Mn levels, and resolution of polycythemia. We wish to highlight the atypical
      neurologic presentation, a novel missense mutation, and beneficial effect of EDTA
      in this rare disease.

PMID- 29179236
TI  - Moyamoya Syndrome Manifesting with Choreiform Movements.

PMID- 29179237
TI  - Older Age and Longer Epilepsy Duration Do Not Predict Worse Seizure Reduction
      Outcome after Vagus Nerve Stimulation.
AB  - INTRODUCTION:  We analyzed the results of vagus nerve stimulation (VNS) on older
      patients and patients with long-lasting epilepsy and included severely
      intellectually disabled patients. PATIENTS AND METHODS:  A total of 103 adults
      with VNS implanted from 2005 to 2014 were studied. The responder rates, that is,
      the percentage of VNS patients who responded to VNS, classified as seizure
      reduction >= 50% (50R) and seizure reduction >= 90% (90R), were compared in
      defined age groups (< 40 and >= 40 years, and < 50 and >= 50 years) and epilepsy
      duration groups (< 20 and >= 20 years, < 30 and >= 30 years, and < 40 and >= 40
      years) at the 1-year follow-up visit and the last follow-up visit (at least 2
      years after surgery). The age distributions and responder rates were also studied
      in patients with an intellectual disability. RESULTS:  The analysis did not
      confirm a significantly lower 50R or 90R rate in patients >= 40, >= 50, or >= 60
      years when compared with their younger counterparts, but the 50R rate increase
      during follow-up care was the lowest in patients >= 50 and >= 60 years. The
      highest percentage of patients with an intellectual disability in the group < 40
      years of age did not adversely affect the 50R rate. Longer epilepsy duration was
      not confirmed as a negative predictor of VNS outcome. There was a significantly
      higher 50R rate in patients with epilepsy duration >= 20 years (at the last
      follow-up visit) and a higher 90R rate in patients with epilepsy duration >= 30
      years (at the 1-year follow-up visit). The increase in the 50R rate during follow
      up care was lower in patients with epilepsy durations >= 30 and >= 40 years.
      CONCLUSIONS:  The study did not find worse VNS outcomes, as defined by the 50R or
      90R rate, in older adult patients or in patients with a longer epilepsy duration.
      The increasing stimulation effect over time is less marked in older patients and
      in patients with longer epilepsy duration.

PMID- 29179238
TI  - Modic Type 1 Changes: Detection Performance of Fat-Suppressed Fluid-Sensitive MRI
      Sequences.
AB  - PURPOSE:  To assess the performance of fat-suppressed fluid-sensitive MRI
      sequences compared to T1-weighted (T1w) / T2w sequences for the detection of
      Modic 1 end-plate changes on lumbar spine MRI. MATERIALS AND METHODS:  Sagittal
      T1w, T2w, and fat-suppressed fluid-sensitive MRI images of 100 consecutive
      patients (consequently 500 vertebral segments; 52 female, mean age 74 +/- 7.4
      years; 48 male, mean age 71 +/- 6.3 years) were retrospectively evaluated. We
      recorded the presence (yes/no) and extension (i. e., Likert-scale of height,
      volume, and end-plate extension) of Modic I changes in T1w/T2w sequences and
      compared the results to fat-suppressed fluid-sensitive sequences
      (McNemar/Wilcoxon-signed-rank test). RESULTS:  Fat-suppressed fluid-sensitive
      sequences revealed significantly more Modic I changes compared to T1w/T2w
      sequences (156 vs. 93 segments, respectively; p < 0.001). The extension of Modic
      I changes in fat-suppressed fluid-sensitive sequences was significantly larger
      compared to T1w/T2w sequences (height: 2.53 +/- 0.82 vs. 2.27 +/- 0.79, volume:
      2.35 +/- 0.76 vs. 2.1 +/- 0.65, end-plate: 2.46 +/- 0.76 vs. 2.19 +/- 0.81), (p <
      0.05). Modic I changes that were only visible in fat-suppressed fluid-sensitive
      sequences but not in T1w/T2w sequences were significantly smaller compared to
      Modic I changes that were also visible in T1w/T2w sequences (p < 0.05).
      CONCLUSION:  In conclusion, fat-suppressed fluid-sensitive MRI sequences revealed
      significantly more Modic I end-plate changes and demonstrated a greater extent
      compared to standard T1w/T2w imaging. KEY POINTS:   . When the Modic
      classification was defined in 1988, T2w sequences were heavily T2-weighted and
      thus virtually fat-suppressed.. . Nowadays, the bright fat signal in T2w images
      masks edema-like changes.. . The conventional definition of Modic I changes is
      not fully applicable anymore.. . Fat-suppressed fluid-sensitive MRI sequences
      revealed more/greater extent of Modic I changes.. CITATION FORMAT: . Finkenstaedt
      T, Del Grande F, Bolog N et al. Modic Type 1 Changes: Detection Performance of
      Fat-Suppressed Fluid-Sensitive MRI Sequences. Fortschr Rontgenstr 2018; 190: 152 
      160.

PMID- 29179240
TI  - Assessment of Length of Maternal Cervix between 18 and 24 weeks of Gestation in a
      Low-Risk Brazilian Population.
AB  - Purpose To determine cervical biometry in pregnant women between 18 and 24 weeks
      of gestation and the ideal mode of measurement of cervical length in cases of
      curved and straight cervical morphology. Methods The uterine cervices of 752 low
      risk pregnant women were assessed using transvaginal ultrasound in a prospective
      cross-sectional study. In women with straight uterine cervices, cervical biometry
      was performed in a continuous manner. In women with curved uterine cervices, the
      biometry was performed using both the continuous and segmented techniques (in
      segments joining the cervical os). Polynomial regression models were created to
      assess the correlation between the cervical length and gestational age. The
      paired Student t-test was used to compare measuring techniques. Results The
      cervical biometry results did not vary significantly with the gestational age and
      were best represented by linear regression (R2 = 0.0075 with the continuous
      technique, and R2 = 0.0017 with the segmented technique). Up to the 21st week of
      gestation, there was a predominance of curved uterine cervix morphology (58.9%),
      whereas the straight morphology predominated after this gestational age (54.2%).
      There was a significant difference between the continuous and the segmented
      measuring methods in all the assessed gestational ages (p < 0.001). Conclusion
      Cervical biometry in pregnant women between 18 and 24 weeks was represented by a
      linear regression, independently of the measuring mode. The ideal measuring
      technique was the transvaginal ultrasound performed at a gestational age >=21
      weeks.

PMID- 29179239
TI  - Value of multiparametric magnetic resonance imaging of the breast for the
      differentiation of fat necrosis and tumor recurrence after breast-conserving
      surgery: A case report.

PMID- 29179241
TI  - Mandibular Inferior Cortex Erosion on Dental Panoramic Radiograph as a Sign of
      Low Bone Mineral Density in Postmenopausal Women.
AB  - Objective To examine the role of the panoramic mandibular radiograph in the
      diagnosis of low bone mineral density (BMD) in postmenopausal women. Methods A
      cross-sectional study including volunteer women aged over 40 years in amenorrhea
      due to ovarian failure for at least 12 months, who were cared for at the
      climacteric outpatient clinic of a university hospital in the city of Cuiaba, in
      the state of Mato Grosso, Brazil. The panoramic radiographs were evaluated using
      a specific software. Two aspects were analyzed in the mandibular panoramic
      radiograph: a qualitative aspect regarding the shape of the mandibular cortical
      bone, and a quantitative aspect regarding the width of the mandibular cortical
      bone. The morphology of the mandibular cortical bone in the digital panoramic
      radiograph was determined bilaterally by the observation of the bone structure
      between the mental foramen and the base of the jaw. The mandibular cortical bone
      was categorized into three groups. The mental index (MI) was used to evaluate the
      thickness of the mandibular cortical bone through a perpendicular line drawn from
      the base of the mandible at the height of the center of the mental foramen, with
      another line drawn tangent to the inferior border of the mandible, and a third
      line parallel to the line at the superior border of the mandible. The MI data are
      expressed in millimeters, with a normal value of 3.0 mm. The densities of the
      lumbar spine and femur, expressed in g/cm2, were categorized as normal,
      osteopenia or osteoporosis. Results The agreement index between the MI and the
      BMD of the lumbar spine was good (Kappa = 0.718), but the same index between the
      MI and the BMD of the femoral neck was poor (Kappa = 0.443). An excellent
      agreement occurred when the mandibular cortical index (MCI) was compared with the
      BMD of the lumbar spine (Kappa = 0.912). The agreement between MCI and the BMD in
      the femur was moderated (Kappa = 0.579). Conclusion The radiomorphometric indices
      evaluated in the mandibular panoramic radiograph are capable of identifying
      postmenopausal women with low mineral density in the mandible, and the results
      can be used to refer these women to appropriate medical investigation and/or
      treatment.

PMID- 29179243
TI  - Pyelonephritis in Pregnancy: Clinical and Laboratorial Aspects and Perinatal
      Results.
AB  - Objective To identify the prevalence of pyelonephritis during pregnancy and to
      analyze the clinical and laboratorial aspects, perinatal results and
      complications. Methods A transversal study of 203 pregnant women who had
      pyelonephritis during pregnancy and whose labor took place between 2010 and 2016
      at a hospital in the state of Santa Catarina, Brazil. The analysis was based on
      medical records as well as on the hospital's database. Clinical and laboratory
      conditions, antibiotics, bacterial resistance, perinatal outcomes and
      complications were all taken into account. The data was compared using the Mann
      Whitney test and the Chi-square test. Results A prevalence of 1.97% with
      pyelonephritis was evidenced, with most patients having it during the second
      trimester of gestation. The bacteria most commonly found in the urine cultures
      was Escherichia coli, in 76.6% of cases, followed by Klebsiella pneumoniae
      (8.7%). Ceftriaxone had the lowest bacterial resistance (only 3.5% of the cases).
      On the other hand, ampicillin and cephalothin presented higher bacterial
      resistance, 52% and 36.2%, respectively. The risk of very premature delivery was
      more than 50% higher in patients with pyelonephritis. Conclusion Ampicillin and
      first-generation cephalosporins are associated with a higher bacterial resistance
      while ceftriaxone proved to have a high efficacy for the treatment of
      pyelonephritis due to low bacterial resistance. Patients with pyelonephritis
      showed a higher risk for very premature delivery (< 32 weeks). In this casuistry,
      there were no others significant differences in the overall perinatal outcomes
      when compared with the routine service series.

PMID- 29179244
TI  - Is Ovarian Cancer Prevention Currently Still a recommendation of Our
      Grandparents?
AB  - Ovarian cancer is the leading cause of death among gynecologic tumors because in
      most of the cases (75%), the disease is diagnosed in advanced stages. Screening
      methods are not available since the disease is rare, and the tested methods, such
      as ultrasound and CA125, were not able to decrease the mortality rate for this
      type of cancer. This article discusses the main risk factors for ovarian cancer,
      and the potential clinical and surgical strategies for the prevention of this
      disease.

PMID- 29179242
TI  - Distance Education Course about Sexuality for Obstetrics and Gynecology
      Residents.
AB  - Purpose To describe the experience of a distance education course on sexual
      issues during pregnancy and after birth for residents. Methods This prospective
      educational intervention study was conducted by investigators from the
      Universidade Federal de Sao Paulo, Brazil, between April and September 2014. The
      participants were 219 physicians (residents from the 1st to the 6th years). The
      duration of the course was of 24 hours (10 video lectures and online chats). At
      baseline, the participants answered questions about their training, attitude and
      experience regarding sexual issues during pregnancy and after birth; before and
      after the course, they answered questions to assess their knowledge about the
      topic; at the end of the course, they answered questions on the quality of the
      course. The Student t-test was used to compare the before and after scores of the
      knowledge tests; values of p < 0.05 were considered statistically significant.
      Results A total of 143 residents concluded the course; most were in their 1st
      (27.2%) or 3rd (29.4%) years of residency. There was a significant increase in
      the mean scores of the questionnaires that assessed the knowledge of the topic:
      4.4 (+/-1.6) versus 6.0 (+/-1.3; maximum score: 10), before and after the course
      respectively (p < 0.0001). Most of the participants (74.1%) declared that the
      quality of the course as a whole reached their expectations, and 81.1% would
      recommend the course to a friend. Conclusions The online Sexology course for
      Obstetrics and Gynecology residents increased their knowledge about the sexual
      issues during pregnancy and after birth, and fulfilled the participants'
      expectations. The experience described here may serve as a model for other
      sexuality courses targeting similar audiences.

PMID- 29179245
TI  - Anti-inflammatory Effects of Canthin-6-one Alkaloids from Ailanthus altissima.
AB  - Canthin-6-one (CO) alkaloids possess various biological activities, including
      antibacterial, antitumor, antifungal, and antiviral activities. However, their
      anti-inflammatory effects and underlying molecular mechanisms are poorly
      characterized. This study aimed to investigate the anti-inflammatory effects of
      CO and its derivative 5-(1-hydroxyethyl)-canthin-6-one (5-HCO), isolated from the
      stem barks of Ailanthus altissima in lipopolysaccharide (LPS)-stimulated
      macrophages. CO (1 and 5 uM) and 5-HCO (7.5 and 15 uM) significantly inhibited
      the LPS-induced expression of inducible nitric oxide synthase. In addition, CO (1
      and 5 uM) and 5-HCO (15 uM) markedly suppressed the production of prostaglandin
      E2 (PGE2) and expression of cyclooxygenase-2, a key enzyme in PGE2 synthesis, in
      LPS-stimulated macrophages. Moreover, CO treatment significantly reduced monocyte
      chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha)
      expression, whereas 5-HCO inhibited MCP-1, but not TNF-alpha expression. Both CO
      and 5-HCO inhibited the phosphorylation of inhibitor kappa B and transcriptional
      activation of nuclear factor kappa B (NF-kappaB) in LPS-stimulated macrophages.
      In addition, CO, but not 5-HCO, markedly reduced Akt phosphorylation. Taken
      together, these data suggest that CO, but not 5-HCO with a hydroxyethyl moiety on
      the D ring, has potent anti-inflammatory activity in LPS-stimulated macrophages
      through the downregulation of both the NF-kappaB and the Akt pathway.

PMID- 29179247
TI  - The Developing Role of Anti-Epidermal Growth Factor Receptor Agents in the
      Treatment of Advanced or Metastatic Colorectal Cancer.
AB  - The first studies of epidermal growth factor receptor (EGFR) inhibitors in
      metastatic colorectal cancer were begun before the predictive role of RAS
      mutations had been elucidated. Secondary analyses of many large randomized trials
      have shown that mutations in exons 2-4 of KRAS and NRAS, BRAF V600E mutation, and
      right-sided primary tumor all predict lack of response to EGFR inhibition in the
      first-line setting. However, even in patient populations defined by a lack of
      these negative predictors, there is still not uniform response to anti-EGFR
      therapy. Additionally, although older adults have been shown to have the
      potential to both tolerate and respond to anti-EGFR therapy, the criteria for
      selecting the most appropriate older patients for treatment remain unclear.

PMID- 29179248
TI  - Radical Prostatectomy for Patients With Oligometastatic Prostate Cancer.
AB  - Cancer progresses in a stepwise fashion. Oligometastatic cancer is an
      intermediate stage of tumor spread between localized disease and disseminated
      metastases. Oligometastatic prostate cancer is defined as up to five extrapelvic
      lesions on conventional imaging. There are controversies surrounding the
      management of this malignancy, but retrospective and population-based studies
      suggest a role for radical prostatectomy. Despite insufficient data to draw
      conclusions regarding the effectiveness of aggressive therapies on overall or
      cancer-specific survival of patients with oligometastatic prostate cancer,
      current studies suggest that surgery decreases tumor burden, disease-related
      morbidity, and the need for palliative surgical intervention, while increasing
      the period of time to development of castration-resistant disease.

PMID- 29179249
TI  - Judy Garber on PARP Inhibitors for Triple-Negative Breast Cancer.

PMID- 29179250
TI  - PI3K Inhibitors: Understanding Toxicity Mechanisms and Management.
AB  - The phosphatidylinositol 3-kinase (PI3K) pathway has attracted immense interest
      as a therapeutic target for cancer treatment. Idelalisib was the first PI3K
      inhibitor approved by the US Food and Drug Administration and is utilized in the
      treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic
      lymphoma and follicular lymphoma. Copanlisib has subsequently been approved for
      relapsed follicular lymphoma in patients who have received at least two prior
      systemic therapies. There are multiple other PI3K agents currently in
      development; these target various combinations of PI3K isoforms. Despite the
      therapeutic benefit, there have been concerns about the severe and sometimes
      fatal adverse effects of this class of drug. Several side effects are unusual and
      have poorly understood mechanisms; these include autoimmune dysfunction,
      opportunistic infections, skin toxicity, hypertension, and hyperglycemia. An
      understanding of these unusual toxicities, as well as a good grasp of management
      principles, will be important as more PI3K inhibitors are approved and become
      incorporated into routine practice.

PMID- 29179251
TI  - Point: Which Treatment Modality for Localized Prostate Cancer Yields Superior
      Quality of Life: Radiotherapy or Prostatectomy? Quality of Life is Better After
      Modern Radiotherapy Compared With Surgery.

PMID- 29179252
TI  - Counterpoint: Which Treatment Modality for Localized Prostate Cancer Yields
      Superior Quality of Life: Radiotherapy or Prostatectomy? Most Men With Clinically
      Important Localized Prostate Cancer Deserve First-Line Open or Robotic Radical
      Prostatectomy.

PMID- 29179253
TI  - Mucosal Melanoma: New Insights and Therapeutic Options for a Unique and
      Aggressive Disease.
AB  - Mucosal melanoma is a rare disease that is distinct from melanomas arising at
      other sites in the body. While melanocytes are most abundant in the skin, they
      can be found in smaller numbers in the mucous membranes, as well as in the eye.
      There are epidemiologic, genetic, and other physiologic differences between
      melanomas arising from melanocytes at these various sites, and these differences
      have important implications for both disease prognosis and treatment. Here, we
      review the features of mucosal melanoma that distinguish it from melanomas
      arising at other sites, and we highlight recent biological discoveries and
      emerging treatment options for this aggressive disease.

PMID- 29179254
TI  - The structure of DLP12 endolysin exhibiting alternate loop conformation and
      comparative analysis with other endolysins.
AB  - The lytic enzyme, endolysin, is encoded by bacteriophages (phages) to destroy the
      peptidoglycan layer of host bacterial cells. The release of phage progenies to
      start the new infection cycle is dependent on the cell lysis event. Endolysin
      encoded by DLP12 cryptic prophage is a SAR endolysin which is retained by the
      bacterium presumably due to the benefit it confers. The structure of DLP12
      endolysin (Id: 4ZPU) determined at 2.4 A resolution is presented here. The DLP12
      endolysin structure shows a modular nature and is organized into distinct
      structural regions. One of the monomers has the loops at the active site in a
      different conformation. This has led to a suggestion of depicting possibly active
      and inactive state of DLP12 endolysin. Comparison of DLP12 endolysin structure
      and sequence with those of related endolysins shows the core three-dimensional
      fold is similar and the catalytic triad geometry is highly conserved despite the
      sequence differences. Features essential for T4 lysozyme structure and function
      such as the distance between catalytic groups, salt bridge and presence of
      nucleophilic water are conserved in DLP12 endolysin and other endolysins
      analyzed.

PMID- 29179255
TI  - Excess overdose mortality immediately following transfer of patients and their
      care as well as after cessation of opioid substitution therapy.
AB  - AIMS: To investigate clustering of all-cause and overdose deaths after a transfer
      of patients and their care to alternative treatment provider and after the end of
      opioid substitution therapy (OST) in opioid-dependent individuals in specialist
      addiction treatment. DESIGN, SETTING AND PARTICIPANTS: Mortality data were
      identified within a sample of 5335 patients with opioid use disorder who had
      received OST treatment between 1 April 2008 and 31 December 2013 from a large
      mental health-care provider in the United Kingdom. We investigated the
      circumstances and distribution of the 332 deaths identified within the
      observation window with a specific focus on overdose deaths (n = 103) after a
      planned discharge, dropout and transfer between services. MEASUREMENTS: Crude
      mortality rates for overdose mortality 14 days, 28 days and more than 1 month
      after the end of treatment/transfer for overdose mortality. FINDINGS: Of 47
      individuals who died from overdose after having been transferred between
      services, nine died during the first 2 weeks [crude mortality rate (CMR) = 136.4,
      95% confidence interval (CI) = 64.3-243.1] and a further five died during the
      first month post-transfer (CMR= 79.5, 95% CI = 44.2-129.7). Of the 32 individuals
      who died from overdose after planned OST cessation, five died during the first 2
      weeks (CMR = 151.5, 95% CI = 51.1-319.0) and a further four died during the first
      month post-discharge (CMR = 82.6, 95% CI = 38.4-151.0). CONCLUSIONS: In the
      United Kingdom, opioid-dependent people who are transferred to an alternative
      treatment provider for continuation of their opioid substitution therapy
      experience high overdose mortality rates, with substantially higher rates during
      the first month (especially during the first 14 days) following transfer.

PMID- 29179256
TI  - SYNJ1 gene associated with neonatal onset of neurodegenerative disorder and
      intractable seizure.
AB  - BACKGROUND: Synaptojanin 1 is encoded by the SYNJ1(MIM 604297) and plays a major
      role in phosphorylation and recycling of synaptic vesicles. Mutation of SYNJ1 is
      associated with two distinct phenotypes; a known homozygous missense mutation
      (p.Arg258Gln) associated with early-onset Parkinson disease (MIM 615530), whereas
      mutation with complete loss of SYNJ1 function result in a lethal
      neurodegenerative disease with intractable seizure and tauopathies (MIM 617389).
      METHODS: We report two related children from consanguineous family presented with
      intractable seizure, profound developmental delay, failure to thrive, acquired
      microcephaly, and hypotonia. The brain MRI is normal and EEG showed
      hypsarrhythmia. RESULT: The diagnosis was achieved via whole-genome sequencing
      which showed homozygous mutation in SYNJ1 (c.709C>T, p.Gln237*). CONCLUSION: A
      clinical pattern of neonatal-onset intractable seizure, profound developmental
      delay, muscular hypotonia, hypsarrhythmia, and no focal abnormality of brain MRI
      should prompt initiation of molecular genetic analysis of SYNJ1. Establishment of
      the diagnosis permits genetic counseling, prevents patients undergoing unhelpful
      diagnostic procedures and allows for accurate prognosis.

PMID- 29179257
TI  - Is the FSHR 2039A>G variant associated with susceptibility to testicular germ
      cell cancer?
AB  - Testicular germ cell cancer (TGCC) is derived from germ cell neoplasia in situ
      (GCNIS), which arises due to niche disturbances affecting the Sertoli cells. It
      is believed that exogenous endocrine factors have a crucial role in governing
      neoplastic transformation but on a strong hereditary background. Follicle
      stimulating hormone (FSH) is the major regulatory hormone of the Sertoli cells.
      FSH signalling-related single-nucleotide polymorphisms (SNPs) have previously
      been shown to affect FSH action in men at different levels. We aimed to
      investigate whether three FSH-related SNPs (FSHR 2039A>G, FSHR -29G>A and FSHB 
      211G>T) are associated with development of TGCC. A total of 752 Danish and German
      patients with TGCC from two tertiary andrological referral centres were included.
      Three control groups comprising 2020 men from the general population, 679 fertile
      men and 417 infertile men, were also included. Chi-squared test was performed to
      compare genotype- and allele frequencies. Kruskal-Wallis test was performed to
      compare age at diagnosis. Patients with TGCC had a higher frequency of the A
      allele of FSHR 2039A>G compared to the group of fertile men with an AA-genotype
      frequency of 30.2% vs. 22.0%, respectively, p = 0.002. This variant is associated
      with higher FSH receptor activity. The distribution of the FSHR 2039A>G did not
      differ significantly between the patients with TGCC and the infertile or the
      general population. The frequency of the two other SNPs did not differ between
      patient with TGCC and any of the control groups. No differences were detected
      between genotypes and age distribution or histological subtype of the tumours. In
      conclusion, we observed that a genetic variant associated with FSHR activity may
      modulate the susceptibility to TGCC.

PMID- 29179258
TI  - Increased risk of autoimmune disorders in infertile men: analysis of US claims
      data.
AB  - Aberrations in reproductive fitness may be a harbinger of medical diseases in
      men. Existing data suggest that female infertility is associated with autoimmune
      disorders; however, this has not been examined in men. As immune surveillance and
      hormonal factors can impact male fertility and autoimmunity, we sought to
      determine the association between male infertility and incident autoimmune
      disorders. We analyzed subjects from the Truven Health MarketScan claims database
      from 2001 to 2008. Infertile men were identified through diagnosis and treatment
      codes. We examined the most common immune disorders, which were identified by
      ICD9 diagnosis codes. Men diagnosed with an immune disorder at baseline or within
      1 year of follow-up were excluded. Infertile men were compared to vasectomized
      men (i.e., men who are likely fertile) and to age-matched control (10 : 1) group
      using Cox regression analysis. A total of 33,077 infertile men (mean age of 33
      years), 77,693 vasectomized men (mean age 35), and 330,770 age-matched control
      men (mean age 33) were assembled with a total follow-up of 1.49 M person-years.
      Overall, immune disorders were rare in the group with the individual conditions
      occurring in <0.1% of men. However, infertile men displayed the highest risk of
      many conditions. Infertile men had a higher risk of developing rheumatoid
      arthritis compared to both vasectomized men (HR 1.56, 95% CI 1.19-2.05) and age
      matched controls (HR 1.29, 95% CI 1.02-1.62). Additionally, this higher risk was
      seen in general immune disorders (under which systemic lupus erythematosus is
      categorized) compared to vasectomized men (HR 3.11, 95% CI 2.00-4.86) and age
      matched men (HR 2.12, 95% CI 1.52-2.96). This same risk trend was seen in
      psoriasis, when compared to vasectomized men (HR 1.28, 95% CI 1.09-1.50) and age
      matched controls (HR 1.20, 95% CI 1.04-1.37). A similar trend was seen in the
      analysis comparing infertile men and vasectomized men in developing multiple
      sclerosis (HR 1.91, 95% CI 1.10-3.31) and Grave's disease (HR 1.46, 95% CI 1.10
      1.92), as well as the higher risk of infertile men compared to the age-matched
      group at developing thyroiditis (HR 1.60, 95% CI 1.02-2.52). The current analysis
      shows that infertile men have a higher risk of developing certain autoimmune
      disorders in the years following an infertility evaluation. Specifically,
      infertile men had higher rates of developing rheumatoid arthritis, multiple
      sclerosis, psoriasis, thyroiditis, and Grave's disease. Given these findings,
      further research should focus on confirmation of these associations and
      elucidation of the pathways between fertility and immunity.

PMID- 29179259
TI  - Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders.
AB  - Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the
      human testis. We have reported the crystal structure, instability of the H3.5
      nucleosome and accumulation around transcription start sites, mainly in primary
      spermatocytes, but its role in human spermatogenesis remains poorly understood.
      Testicular biopsy specimens from 30 men (mean age: 35 years) with non-obstructive
      azoospermia (NOA) who underwent microdissection testicular sperm extraction and
      23 men with obstructive azoospermia (OA) were included. An H3.5-specific mouse
      monoclonal antibody recognizing an H3.5-specific synthetic peptide was generated,
      and immunohistological staining for H3.5 and proliferating cell nuclear antigen
      (PCNA) was performed on Bouin's solution-fixed sections. Expression and
      localization of H3.5 were compared with patient background, germinal stage, and
      PCNA expression. In testes of patients with normal spermatogenesis,
      differentially expressed H3.5 was specifically localized in either spermatogonia
      or preleptotene/leptotene-stage primary spermatocytes, especially during germinal
      stages VI-X. In NOA testes, mRNA expression of H3.5 (H3F3C) was significantly
      reduced compared with other H3 histone family members, and expression of H3.5 was
      significantly lower than that in OA. Additionally, the number of H3.5-positive
      germ cells was higher in hypospermatogenesis or late maturation arrest than in
      early maturation arrest in NOA testes (p < 0.01). A significant positive
      correlation was observed between H3.5 and PCNA expression (p < 0.05) but not
      TUNEL-positive cells, and expression of H3.5 was enhanced after hCG-based salvage
      hormonal therapy. Different from other testis-specific histones, which are often
      expressed during the histone-to-protamine transition during meiosis, H3.5 was
      expressed mainly in immature germ cells. H3.5 may play roles in DNA synthesis,
      but not apoptosis, and its expression is regulated by gonadotropins, indicating
      that such epigenetic regulations are important in normal spermatogenesis and
      spermatogenic disorders.

PMID- 29179260
TI  - Naringenin attenuates highly active antiretroviral therapy-induced sperm DNA
      fragmentations and testicular toxicity in Sprague-Dawley rats.
AB  - Highly active antiretroviral therapy has evolved over the years, leading to a
      boost in the quality of life in people living with HIV and AIDS. However, growing
      evidence has shown that highly active antiretroviral therapy has deleterious
      effects on the testes and the overall reproductive capacity. Therefore, this
      study is to determine the adjuvant potential of Naringenin on highly active
      antiretroviral therapy-induced perturbations in fertility of male Sprague-Dawley
      rats. Thirty adult male Sprague-Dawley rats were divided into six groups viz -
      Control; H: 30 mg/kg of highly active antiretroviral therapy (EFV, 600 mg + FTC,
      200 mg + TDF, 300 mg); N40: Naringenin, 40 mg/kg; N80: Naringenin, 80 mg/kg;
      HN40: highly active antiretroviral therapy + Naringenin, 40 mg/kg; HN80: highly
      active antiretroviral therapy + Naringenin, 80 mg/kg. The rats were euthanized
      after 4 weeks. Results showed that there was a significant decrease in sperm
      count (p < 0.001), spermatozoa with normal morphology (p < 0.001) and progressive
      sperm motility (p < 0.05) of H compared to the control and the HN groups.
      Likewise, fragmentations increased (p < 0.05) in tail lengths of sperm DNA in H
      compared to control. HN40 and HN80 decreased tail lengths compared to H (p <
      0.001). There was also a decrease in %tail DNA and tail moment in HN40 (p <
      0.001) compared to H. Luteinizing hormone significantly increased (p < 0.05) in
      HN40, HN80, and N40 (p < 0.001) but decreased in H (p < 0.05) compared to
      control. The diameter of the seminiferous tubules also decreased (p < 0.05) in H
      compared to control, N80, and HN40. Likewise, the area of the seminiferous
      tubules in group H decreased (p < 0.05) compared to N80 and HN80. The
      seminiferous tubules epithelium increased (p < 0.05) in N40 and HN40 compared to
      H. This study establishes that highly active antiretroviral therapy has
      deleterious effects on the testicular microanatomy, sperm parameters, and sperm
      DNA of Sprague-Dawley rats, which may impair fertility but Naringenin is a
      potential complimentary adjuvant.

PMID- 29179261
TI  - Targeted Base Editing via RNA-Guided Cytidine Deaminases in Xenopus laevis
      Embryos.
AB  - Genome editing using programmable nucleases such as CRISPR/Cas9 or Cpf1 has
      emerged as powerful tools for gene knock-out or knock-in in various organisms.
      While most genetic diseases are caused by point mutations, these genome-editing
      approaches are inefficient in inducing single-nucleotide substitutions. Recently,
      Cas9-linked cytidine deaminases, named base editors (BEs), have been shown to
      convert cytidine to uridine efficiently, leading to targeted single-base pair
      substitutions in human cells and organisms. Here, we first report on the
      generation of Xenopus laevis mutants with targeted single-base pair substitutions
      using this RNA-guided programmable deaminase. Injection of base editor 3 (BE3)
      ribonucleoprotein targeting the tyrosinase (tyr) gene in early embryos can induce
      site-specific base conversions with the rates of up to 20.5%, resulting in
      oculocutaneous albinism phenotypes without off-target mutations. We further test
      this base-editing system by targeting the tp53 gene with the result that the
      expected single-base pair substitutions are observed at the target site.
      Collectively, these data establish that the programmable deaminases are efficient
      tools for creating targeted point mutations for human disease modeling in
      Xenopus.

PMID- 29179262
TI  - Advances towards Controlling Meiotic Recombination for Plant Breeding.
AB  - Meiotic homologous recombination generates new combinations of preexisting
      genetic variation and is a crucial process in plant breeding. Within the last
      decade, our understanding of plant meiotic recombination and genome diversity has
      advanced considerably. Innovation in DNA sequencing technology has led to the
      exploration of high-resolution genetic and epigenetic information in plant
      genomes, which has helped to accelerate plant breeding practices via high
      throughput genotyping, and linkage and association mapping. In addition, great
      advances toward understanding the genetic and epigenetic control mechanisms of
      meiotic recombination have enabled the expansion of breeding programs and the
      unlocking of genetic diversity that can be used for crop improvement. This review
      highlights the recent literature on plant meiotic recombination and discusses the
      translation of this knowledge to the manipulation of meiotic recombination
      frequency and location with regards to crop plant breeding.

PMID- 29179263
TI  - Odorant Receptors Containing Conserved Amino Acid Sequences in Transmembrane
      Domain 7 Display Distinct Expression Patterns in Mammalian Tissues.
AB  - Mammalian genomes are well established, and highly conserved regions within
      odorant receptors that are unique from other G-protein coupled receptors have
      been identified. Numerous functional studies have focused on specific conserved
      amino acids motifs; however, not all conserved motifs have been sufficiently
      characterized. Here, we identified a highly conserved 18 amino acid sequence
      motif within transmembrane domain seven (CAS-TM7) which was identified by
      aligning odorant receptor sequences. Next, we investigated the expression pattern
      and distribution of this conserved amino acid motif among a broad range of
      odorant receptors. To examine the localization of odorant receptor proteins, we
      used a sequence-specific peptide antibody against CAS-TM7 which is specific to
      odorant receptors across species. The specificity of this peptide antibody in
      recognizing odorant receptors has been confirmed in a heterologous in vitro
      system and a rat-based in vivo system. The CAS-TM7 odorant receptors localized
      with distinct patterns at each region of the olfactory epithelium; septum,
      endoturbinate and ectoturbinate. To our great interests, we found that the CAS
      TM7 odorant receptors are primarily localized to the dorsal region of the
      olfactory bulb, coinciding with olfactory epithelium-based patterns. Also, these
      odorant receptors were ectopically expressed in the various non-olfactory tissues
      in an evolutionary constrained manner between human and rats. This study has
      characterized the expression patterns of odorant receptors containing particular
      amino acid motif in transmembrane domain 7, and which led to an intriguing
      possibility that the conserved motif of odorant receptors can play critical roles
      in other physiological functions as well as olfaction.

PMID- 29179264
TI  - [Guideline for nonimmune hydrops fetalis].

PMID- 29179265
TI  - [Medicine and literature].

PMID- 29179266
TI  - [Challenges and strategies in cervical cancer screening and management of
      cervical lesions].

PMID- 29179267
TI  - [Significance of p16/Ki-67 double immunocytochemical staining in cervical
      cytology ASCUS, LSIL, and ASC-H].
AB  - Objective: To investigate the application value of p16/cell proliferation
      associated nuclear antigen (Ki-67) double-staining and human papillomavirus mRNA
      in the cytological screening. Methods: Two hundred and fifty-one cases who
      suffered from atypical squamous cell of undetermined significance (ASCUS), low
      grade squamous intraepithelial lesion (LSIL), atypical squamous cell-cannot
      exclude high-grade squamous intraepithelial lesion (ASC-H) in ThinPrep cytologic
      test (TCT) were collected in Peking University First Hospital between October
      2015 and March 2016. And p16/Ki-67 double-staining and hybrid capture II (HC-II)
      detection were performed on the cervical cells. The result was compared with the
      pathological result of colposcope guided biopsy. All statistical analysis was
      completed by Stata 12.0 statistical software analysis. The results of diagnostic
      tests were described by using the sensitivity, specificity, positive predictive
      value,negative predictive value, and the area under the receiver operating
      characteristic (ROC) curve. Results: (1) One hundred and eight cases of liquid
      based cytology diagnosis of ASCUS patients, the positive rate of p16/Ki-67 was
      13.9% (15/108), 102 cases of liquid based cytology diagnosis of LSIL patients,
      the positive rate of p16/Ki-67 was 21.6% (22/102), 41 cases of liquid based
      cytology diagnosis of ASC-H patients, the positive rate of p16/Ki-67 was 39.0%
      (16/41), compared amongthree groups, the difference was statistically significant
      (chi(2)=78.516, P<0.05); cervical exfoliated cells p16/Ki-67 expression rate was
      13.0%(28/215) in cervical low-grade lesions [cervical intraepithelial neoplasia
      (CIN) I], which was 69.4%(25/36) in high level lesions (CIN II-III), the
      difference was statistically significant (chi(2)=7.932, P<0.05). (2) The
      specificity of p16/Ki-67 detection and diagnosis were higher than those of HC-II
      in ASCUS, LSIL, and ASC-H (89.8% vs 71.4%, 83.3% vs 15.6%, 88.9% vs 40.7%; all
      P<0.05), meanwhile, the positive predictive value of p16/Ki-67 detection and
      diagnosis exceed those of HC-II in ASCUS, LSIL, and ASC-H (33.3% vs 26.3%, 31.8%
      vs 12.6%, 81.3% vs 38.5%; all P<0.05). Moreover, the ROC curve of p16/Ki-67 were
      bigger than those of HC-II in ASCUS, LSIL, and ASC-H (0.799 vs 0.696, 0.708 vs
      0.531, 0.909 vs 0.561; all P<0.05). Conclusion: For patients with cytological
      diagnosis of ASCUS, LSIL, and ASC-H, p16/Ki-67 double staining method could be
      used as an effective method to assist in the diagnosis of high-grade cervical
      lesions, and the screening efficiency is superior to that of high-rist HPV.

PMID- 29179268
TI  - [Natural changes of high-risk HPV in women with negative for intraepithelial
      lesion or malignancy: a prospective 1 year study].
AB  - Objective: To investigate the natural changes of high-risk HPV (HR-HPV) in women
      with negative for intraepithelial lesion or malignancy (NILM) for regulating HR
      HPV screening. Methods: Four hundred and thirty-three newly-diagnosed women were
      enrolled from January 1st, 2015 to December 31, 2015 in Beijing Obstetrics and
      Gynecology Hospital. The ages of these patients were between 22 and 74 years, the
      average age was (45+/-21) years old. Two hundred and sixty-three cases were less
      than 50 years old, 170 cases were more and equal to 50 years old. One hundred and
      fifty-six cases were HR-HPV positive, 277 cases were HR-HPV negative. Follow up
      tests were conducted for all 433 patients, who were screened by ThinPrep
      cytologic test (TCT) combined with HR-HPV and were diagnosed with NILM, for a
      period of 1 year (at the 3, 6, 9 and 12 months intervals respectively), if the
      TCT results are abnormal and the HR-HPV test results are positive, will follow up
      colposcopy directed cervical biopsy. Results: (1) HR-HPV natural changes: of 156
      NILM cases with HR-HPV infection, 42 cases (26.9%, 42/156) turned negative within
      3 months, 88 cases (56.4%, 88/156) turned negative within 6 months, 99 cases
      (63.5%, 99/156) turned negative within 9 months, and 100 cases (64.1%, 100/156)
      turned negative within 12 months. The negative conversion ratio at 3, 6, 9 and 12
      months for women at childbearing age (<50 years) were significantly higher than
      those at non-childbearing age (>=50 years old; all P<0.05). Of 277 NILM cases
      without HR-HPV infection, 35 cases (12.6%, 35/277) had new HR-HPV positive
      infections within 3 months, 70 cases (25.3%, 70/277) had new infections within 6
      months, 80 cases (28.9%, 80/277) had new infections within 9 months, and 83 cases
      (30.0%, 83/277) had new infections within 12 months. The new infections rate at
      3, 6, 9 and 12 months for women at childbearing age (<50 years old) were slightly
      higher than those at non-childbearing age (>=50 years old; all P>0.05). (2) The
      progress of cervical leision: of 156 NILM cases with HR-HPV positive, no case
      progressed during 12 months follow-up. Of 277 NILM cases with HR-HPV negative, 4
      cases progressed to cervical intraepithelial neoplaisa (CIN) with HR-HPV
      infection and TCT abnormal during 12 months follow-up, including 2 cases
      pathology diagnosed with CINI, 1 case with CINII, and 1 case with CINIII. The
      progression rate was 1.4%(4/277), which accounts for 4.8% (4/83) of new HR-HPV
      infections cases in women. Conclusions: The results of cytology combined with HR
      HPV screenings suggest every 6 months for simple HR-HPV positive women,
      colposcopy directed cervical biopsy is recommended to assess cervical lesions if
      necessary. Cytology combined with HR-HPV screenings suggest every 12 months for
      simple HR-HPV negative women to early detection of cervical leision.

PMID- 29179269
TI  - [Study on clinical management of HPV(+)/Pap(-) during cervical cancer screening].
AB  - Objective: To study the clinical management way for HPV(+)/papanicolaou (Pap)(-)
      during cervical cancer screening. Methods: To analyze retrospectively the data
      from the patients who had loop electrical excision procedure (LEEP) for biopsy
      confirmed cervical intraepithelial neoplasia (CIN) II in Peking University
      People's Hospital from Jan. 2010 to Dec. 2014. Results: (1) For biopsy confirmed
      CIN II, HPV positive rate was 98.5% (135/137), Pap test positive [>=atypical
      squamous cell of undetermined significance (ASCUS)] rate was 69.3% (95/137),
      there was significant difference between them (chi(2)=43.32, P<0.01). (2) For the
      42 patients with HPV(+)/Pap(-), whose cytology slides were reviewed again. Among
      them, the interpretations of there were 16 cases confirmed as the same before,
      while 26 cases were changed to abnormal (>=ASCUS). Cytology be misdiagnosed was
      19.0% (26/137) at the first review. Among the 26 cases, 13 (50.0%) cases were
      missed for the little amount of abnormal cells, 8 (30.8%) cases for mild atypical
      morphology changed; the other 5 (19.2%) cases missed for stain problems. (3) For
      the cervical LEEP samples, 37 cases of the pathology diagnosis were upgrade to
      CIN III(+), among them, 2 cases of microinvasive cervical carcinoma, 1 case of
      invasive cancer, 34 cases of CIN III; 37 cases were CINI or no lesion found; 63
      cases were still CIN II. Four to six months later after LEEP, the cytology
      abnormal rate was 11.7% (16/137), and the HR-HPV positive rate was 34.3%
      (47/137). Conclusions: Compared with cytology alone, cytology combined with HPV
      testing increase the sensitivity of cervical high grade lesion. For the cases of
      HPV(+)/Pap(-) cases, the cytology slides should be reviewed. The quality control
      of cervical exfoliate sample collection and interpretation should be
      strengthened. LEEP procedure is not only a treatment method, but also it could
      provide samples to confirm the diagnosis.

PMID- 29179270
TI  - [Clinical outcome and high risk factor for residual lesion analysis of HSIL half
      a year after loop electrosurgical excision procedure: a clinical study of 1 502
      cases].
AB  - Objective: To analyze clinical outcome of high-grade squamous intraepithelial
      lesion (HSIL) half a year after loop electrosurgical excision procedure (LEEP)
      and explore the high risk factor of residual cervical HSIL. Methods: The
      retrospective study was carried out on 1 502 patients who underwent LEEP, with
      HSIL in the LEEP histopathology from January 2011 to December 2013 at Obstetrics
      and Gynecology Hospital of Fudan University to confer the difference between
      residual group and non-residual group after 6 months of the leep conization.
      Patients were followed with ThinPrep cytologic test (TCT), high risk HPV (HR-HPV)
      test, colposcopy guided biopsy (CBD) and endocervical curettage (ECC). The high
      risks of residual cervical HSIL was analyzed. Results: Among 1 502 cases, 48
      (3.20%, 48/1 502) cases suffered HSIL residual disease. Forty cases were
      diagnosed by CBD, 4 cases were diagnosed by ECC. The other 4 cases were both
      positive in CBD and ECC. Residul rate were different among different age groups.
      The residual rate was higher in the age >=50 years old compared to the age below
      50 [9.70% (16/165), 2.39% (32/1 337); chi(2)=25.33, P<0.01]. For post-LEEP
      specimens, both circumference (2.5, 2.8 cm; Z=-3.17, P<0.01) and width [0.6, 0.6
      cm; Z=-2.88, P<0.01) were less in HSIL lesion residual group than those in non
      residual group, though length showed no obvious difference [1.5, 1.5 cm; Z=-1.55,
      P>0.05) . The residual rate of leep positive margin was obviously higher than
      that in the negative margin group [6.77% (18/266) vs 2.43% (30/1 236) ;
      chi(2)=13.30, P<0.01]. Different positive margin had diverse residual rate, as
      positive endocervical margin was 16.07% (9/56), positive margin undetermined was
      7.29%(7/96) and positive ectocervical margin was 3.33%(4/120). Both positive
      endocervical margin and positive margin undetermined had a higher residual rate
      than residual rate (chi(2)=26.99, P<0.01; chi(2)=4.24, P<0.05). Abnormal cytology
      showed higher residual rate than the non-residual with significant difference
      [6.00% (6/100) vs 1.29% (14/1 083) , chi(2)=9.50, P<0.01]. In terms of the post
      LEEP HR-HPV test follow-up, HR-HPV positive's residual rate was higher than that
      in the negative group [2.91% (6/206) vs 0.96% (7/727)], while there was no
      statistical significance (chi(2)=3.10, P>0.05). Multivariate logistic analysis
      showed that abnormal cytology in 6 month's follow-up post-LEEP conization was an
      independent risk factor on residual lesion (OR=3.75, P<0.05). Conclusions:
      Patient with age >=50 years old and positive endocervical margin are high risk
      factors for the residual HSIL lesion after LEEP conization,especially for
      abnormal cytology during follow up is independent risk factor for residual
      lesion. Colposcopy directed biopsy and (or) ECC still play an indispendsable role
      in finding the HSIL residual lesion.

PMID- 29179271
TI  - [Relationship between the risk of emergency cesarean section for nullipara with
      the prepregnancy body mass index or gestational weight gain].
AB  - Objective: To investigate the risk of emergency cesarean section during labor
      with the pre-pregnancy body mass index or gestational weight gain. Methods: A
      total of 6 908 healthy nullipara with singleton pregnancy and cephalic
      presentation who was in term labor in Beijing Obstetrics and Gynecology Hospital
      from August 1(st), 2014 to September 30(th), 2015 were recruited. They were
      divided into two groups, the vaginal delivery group (92.88%, 6 416/6 908) and the
      emergency cesarean section group (7.12%, 492/6 908). According to WHO body mass
      index (BMI) classification criteria and the pre-pregnancy BMI, the 6 908 women
      were divided into three groups, the underweight group(BMI<18.5 kg/m(2); 17.39%, 1
      201/6 908), the normal weight group(18.5-24.9 kg/m(2); 73.00%, 5 043/6 908), the
      overweight and obese group (>= 25.0 kg/m(2); 9.61%, 664/6 908). According to the
      guidelines of Institute of Medicine (IOM) , they were divided into three groups,
      the inadequate gestational weight gain (GWG) group (16.72%, 1 155/6 908), the
      appropriate GWG group (43.11%, 2 978/6 908), the excessive GWG group (40.17%, 2
      775/6 908). Unadjusted and adjusted odds ratio (OR) and confidence interval (CI)
      of the risk of emergency cesarean section were calculated by bivariate logistic
      regression. Results: (1) Comparing to the vaginal delivery group, women in the
      emergency cesarean section group were older, with a lower education level. Their
      prepregnancy BMI was higer and had more gestational weight gain. They had higher
      morbidity of pregnancy induced hypertension and gestational diabetes mellitus.
      Comparing to the vaginal delivery group, the neonates in the emergency cesarean
      section group were elder in gestational week, with higher birth weight. More male
      infants and large for gestation age infants were seen in the emergency cesarean
      section group (all P<0.05) . (2) Overweight and obesity were associated with the
      increased risk of emergency cesarean section for nullipara, with the unadjusted
      OR of 1.98 (95%CI: 1.54-2.54), adjusted OR (aOR) of 1.66 (95%CI: 1.27-2.16). In
      the inadequate GWG group and the excessive GWG group, overweight and obese women
      had increased risk of emergency cesarean section, with adjusted OR of 2.33
      (95%CI: 1.06-5.14) and 1.62 (95%CI: 1.44-2.28), respectively. In the appropriate
      GWG group, there was no significant difference in the risk of emergency cesarean
      section between the overweight and obese women and the normal weight women, with
      aOR of 1.54 (95%CI: 0.94-2.54). The underweight group was associated with
      decreased risk of emergency cesarean section (OR=0.55, 95%CI: 0.40-0.74;
      aOR=0.66, 95%CI: 0.48-0.90). While no significant difference in the risk of
      emergency cesarean section was found between the underweight women, the
      overweight and obese women, with the aOR of 0.31 (95%CI: 0.07-1.32), 0.73 (95%CI:
      0.48-1.10), 0.66 (95%CI: 0.38-1.12), respectively. (3) Absolute value of
      gestational weight gain was associated with the increased risk of emergency
      cesarean section, (aOR=1.03, 95%CI: 1.01-1.05). GWG above IOM giudelines did not
      independently affect the risk of emergency cesarean section (OR=1.30, 95%CI: 1.07
      1.58; aOR=1.01, 95%CI: 0.82-1.24). In the underweight group, the normal weight
      group and the overweight or obese group, the excessive GWG women and the
      appropriate GWG women had no significant difference in the risk of emergency
      cesarean section (aOR=1.03, 95%CI: 0.55-1.12; aOR=1.02, 95%CI: 0.80-1.30;
      aOR=1.03, 95%CI: 0.59-1.78) , respectively. GWG below IOM giudelines was
      associated with decreased risk of emergency cesarean section (OR=0.62, 95%CI:
      0.45-0.85; aOR=0.64, 95%CI: 0.46-0.88). In the underweight group and the
      overweight or obese group, there was no significant difference in the emergency
      cesarean section risk between the inadequate GWG women and the appropriate GWG
      within women (aOR= 0.24, 95%CI: 0.06-1.01; aOR= 0.90, 95%CI: 0.40-2.04) . In the
      normal weight group, the inadequate GWG women had lower risk of emergency
      cesarean section (aOR=0.65, 95%CI: 0.45-0.95). Conclusions: Overweight and obese
      women have increased risk of emergency cesarean section. The prepregnancy BMI is
      supposed to be an appropriate level. Absolute value of gestational weight gain is
      associated with increased risk of emergency cesarean section. There is no
      correlation between the excessive GWG and the risk of emergency cesarean section.

PMID- 29179272
TI  - [Analysis of non-invasive prenatal screening detection in fetal chromosome
      aneuploidy].
AB  - Objective: To evaluate the efficacy of non-invasive prenatal screening (NIPS) in
      the detection of fetal aneuploidies. Methods: Cell free DNA was sequenced in 5
      566 pregnant women to identify the fetal aneuploidies in the First Affiliated
      Hospital of Zhengzhou University from January 1(st), 2015 to March 15(th), 2016.
      Among them, 5 230 (93.96%, 5 230/5 566) were singleton pregnancies and 336
      (6.04%, 336/5 566) were twin pregnancies. In singleton pregnancies, 1 809
      (34.59%, 1 809/5 230) were women with advanced maternal age, and 3 421 (65.41%, 3
      421/5 230) were young women. The positive results of NIPS were validated by
      karyotyping through invasive procedures and neonatal outcomes were followed up by
      telephone. Results: Among the 5 566 women, 69 (1.24%, 69/5 566) got positive NIPS
      results, with 66 in singleton pregnancies and 3 in twin pregnancies. Two were
      monochorionic diamniotic twins and 1 was dichorionic twin pregnancy. The positive
      predictive value of NIPS for trisomy 21, 18 and 13 were 100.0%, 90.9% and 100.0%,
      and was 55.6% for sex chromosome aneuploidies. There was no false negative case
      found during the follow-up. In the advanced maternal age group and young women
      group, the prevalence rates of fetal chromosomal aneuploidies were 1.11%(20/1
      809) and 0.94%(32/3 421), respectively. In the young women with soft markers in
      fetal ultrasound, the prevalence of fetal chromosomal aneuploidies was 1.44%
      (7/487), and in serum high risk women, it was 0.94% (7/747). In women with the
      serum screening risk with cut-off value, 0.89%(9/1 016) had fetal aneuploidies,
      and the prevalence was 0.77%(9/1 171) in volunteers. There was no statistically
      significant difference among these groups (P=0.636). Conclusions: There is no
      difference in the detection rate of fetal aneuploidies between high-risk women in
      serum screening and volunteers in NIPS. NIPS is more suitable as a first line
      screening test for women without fetal ultrasound abnormalities. It should be
      used carefully when there is ultrasound abnormalities.

PMID- 29179273
TI  - [Relationship between mitochondrial DNA copy number, membrane potential of human
      embryo and embryo morphology].
AB  - Objective: To explore the relationship between the embryo with the different
      morphological types in the third day and its mitochondrial copy number, the
      membrane potential. Methods: Totally 117 embryos with poor development after
      normal fertilization and were not suitable transferred in the fresh cycle and 106
      frozen embryos that were discarded voluntarily by infertility patients with in
      vitro fertilization-embryo transfer after successful pregnancy were selected.
      According to evaluation of international standard in embryos, all cleavage stage
      embryos were divided into class I frozen embryo group (n=64), class II frozen
      embryo group (n=42) and class III fresh embryonic group (not transplanted
      embryos; n=117). Real-time PCR and confocal microscopy methods were used to
      detect mitochondrial DNA (mtDNA) copy number and the mitochondrial membrane
      potential of a single embryo. The differences between embryo quality and mtDNA
      copy number and membrane potential of each group were compared. Results: The copy
      number of mtDNA and the mitochondrial membrane potential in class III fresh
      embryonic group [(1.7+/-1.0)*10(5) copy/MUl, 1.56+/-0.32] were significantly
      lower than those in class I frozen embryo group [(3.4+/-1.7)*10(5) copy/MUl,
      2.66+/-0.21] and class II frozen embryo group [(2.6+/-1.2)*10(5) copy/MUl, 1.80+/
      0.32; all P<0.05]. The copy number of mtDNA and the mitochondrial membrane
      potential in classI frozen embryo group were significantly higher than those in
      classII frozen embryo group (both P<0.05). Conclusion: The mtDNA copy number and
      the mitochondrial membrane potential of embryos of the better quality embryo are
      higher.

PMID- 29179274
TI  - [A novel HAND1 mutation associated with sporadic dilated cardiomyopathy].
AB  - Objective: To investigate a novel mutation in the HAND1 gene associated with
      sporadic dilated cardiomyopathy (DCM). Methods: From February 2013 to February
      2017, the clinical data and peripheral venous blood samples were collected from
      120 patients with sporadic DCM and 200 healthy controls, who were both from the
      Fifth People's Hospital of Shanghai, Fudan University and Shanghai Chest
      Hospital, Shanghai Jiaotong University.The genomic DNA was extracted from the
      study participants.The coding exons of HAND1 were amplified from the study
      subjects by polymerase chain reaction, and were sequenced for a potential HAND1
      mutation.The online computer programs MUSCLE and Mutation Taster were used to
      analyze the conversation of an altered amino acid and to predict the disease
      causing potential of an identified mutation, respectively.The wild-type HAND1 was
      cloned and the mutant was generated by site-directed mutagenesis.The Dual
      luciferase reporter assay kits were used to explore the functional
      characteristics of the mutant HAND1. Results: A novel heterozygous mutation, a
      substitution of thymine for guanine at nucleotide 346 (c.346G>T), predicting the
      conversion of a glutamic acid-encoding codon into a stop codon at codon 116
      (p.E116X), was detected in a patient with sporadic DCM.The nonsense mutation was
      absent in the 200 control individuals.The altered glutamic acid at amino acid
      position 116 was highly conserved evolutionarily, and the mutation was predicted
      to be pathogenic.Biological analyses revealed that the mutant HAND1 lost the
      ability to transcriptionally activate a target gene. Conclusion: Loss-of-function
      mutation in HAND1 is likely to be an uncommon cause responsible for sporadic DCM.

PMID- 29179275
TI  - [Clinical effectiveness and safety of ticagrelor in patients after PCI because of
      acute non ST segment elevation myocardial infarction].
AB  - Objective: To observe the clinical effectiveness and safety of ticagrelor in
      patients after percutaneous coronary intervention (PCI) because of acute non ST
      segment elevation myocardial infarction (NSTEMI) in China. Methods: A total of
      240 patients with NSTEMI were analyzed retrospectively from Beijing Anzhen
      hospital between Jan 2013 and Jan 2015, with 113 patients in the clopidogrel
      group, 127 in the ticagrelor group. ADP-induced platelet aggregation was
      investigated 1, 3 and 6 month later after PCI, and major adverse cardiac events
      (MACE) and thrombolysis in myocardial infarction (TIMI) bleeding were followed-up
      for 6 months. Results: ADP-induced platelet aggregations of the ticagrelor group
      [(29+/-5)%, (29+/-6)%, (26+/-7)%] were decreased significantly compared with the
      clopidogrel group [(50+/-9)%, (49+/-9)%, (46+/-8)%] 1, 3 and 6 month later after
      PCI (P<0.01). Compared with the clopidogrel group (17.7%), the incidence of MACE
      of ticagrelor group (7.09%) was significantly decreased 6 month later after PCI
      (P<0.05), but there were no statistical differences in the incidence of TIMI
      major bleeding and secondary hemorrhage between the two groups (P>0.05).
      Conclusion: Ticagrelor combined with aspirin can decrease the MACE incidence of
      NSTEMI, and do not increase TIMI major bleeding and secondary hemorrhage.

PMID- 29179276
TI  - [Analysis of contrast echocardiography for detecting right to left shunt in
      adults with patent foramen ovale].
AB  - Objective: To analyze the contrast echocardiography for detecting right to left
      shunt in adults with patent foramen ovale(PFO), and study the relationship
      between PFO and cryptogenic stroke. Methods: Clinical data of forty-six adults
      patients with PFO diagnosed by transesophageal echocardiography(TEE)from March,
      2012 to March, 2017 were retrospectively collected, and the patients were divided
      to 3 groups according to the direction and brightness of the color Doppler
      shunts: obvious left-to-right shunt (OLRS, group A), weak left-to-right
      shunt(WLRS, group B), bi-directional shunt(BDS, group C). A right-to-left shunt
      (RLS) scale was calculated using the method of 10 ml hand-operated saline for
      contrast echocardiography. Results: There were seventeen cases in group A, four
      cases (23.5%) showed RLS at level 1, and thirteen cases (76.5%) showed no RLS;
      there were twenty cases in group B, and all cases (100%) showed RLS, with five
      cases (25%) at level 1 and fifteen cases (75%) at level 2-3; there were nine
      cases in group C, and all cases (100%) showed RLS, with two cases (22.2%) at
      level 1 and seven cases (77.8%) at level 2-3. Anteroposterior diameter of left
      atrium of patients with no RLS (4.8 cm+/-0.6 cm) was significantly larger than
      that of patients with RLS in contrast echocardiography (3.6 cm+/-0.5
      cm)(P=0.000). Conclusions: OLRS of adults with patent foramen ovale and with
      larger left atrium have less RLS than WLRS and DLRS with normal left atrium in
      contrast echocardiography.The possibility of paradoxical embolism in WLRS and
      DLRS is higher than that in OLRS, which should be taken seriously in clinical
      practice.

PMID- 29179277
TI  - [Relationship between frailty and depression in elderly patients].
AB  - Objective: To investigate the relationship between frailty and depression by
      analyzing the clinical data, frailty and depression in the elderly outpatients.
      Methods: This study included outpatients who visited the Geriatric Section of
      West China Hospital from July 1, 2016 to December 31, 2016.Clinical
      characteristics and complications in patients were evaluated comprehensively.The
      debilitating condition of patient was assessed by the international society for
      elderly nutrition simple weakness questionnaire (Fatigue, Resistance, Ambulation,
      Illnesses, Loss of Weight.FRAIL). The depression was assessed by the 30-Item
      Geriatric Depression. Results: Regression analysis showed that pre-frail (OR
      3.286, 95%CI 1.59-3.98) and frail (OR 4.139, 95%CI 1.52-14.40) elder adults had a
      higher risk of depression than other elders. Conclusion: Pre-frail and frail
      elders are at high risk of depression.

PMID- 29179278
TI  - [Expression of macrophage migration inhibitory factor gene in placenta tissue and
      its correlation with gestational diabetes mellitus].
AB  - Objective: To investigate the relationship between the expression of macrophage
      migration inhibitory factor (MIF) gene and the incidence of gestational diabetes
      mellitus (GDM) in Chinese Han population in northern China. Method: This study
      was consisted of 126 GDM women and 150 cases of healthy subjects who came from
      the obstetrics department of Maternity Hospital of Qingdao University and
      Maternity and Child Care Hospital of Donggang District of Rizhao. The protein
      expression of MIF in placenta tissue was detected by Western blot method. The
      blood glucose, insulin levels and other clinical physicochemical index were
      tested. The differences of MIF, fasting blood-glucose (FBG), fasting insulin
      (FIN) and the homeostasis model assessment of insulin resistance (HOMA-IR) were
      compared between the two groups of pregnant women. Result: The level of MIF
      protein in GDM group (0.85+/-0.10) was higher than that in healthy pregnant group
      (0.12+/-0.09), with significant difference (P<0.001). Insulin resistance index in
      GDM group were higher than that in healthy pregnant group, with significant
      difference (P<0.001). Conclusion: The expression of MIF in placental tissues of
      GDM women was increased and correlated with insulin resistance in GDM patients,
      suggesting that MIF may play an important role in the occurrence and development
      of GDM.

PMID- 29179279
TI  - [Exploration of death risk factors in patients with antineutrophil cytoplasmic
      antibody associated vasculitis].
AB  - Objectives: Death risk factors of patients with antineutrophil cytoplasmic
      antibody (ANCA) associated vasculitis (AAV) were explored by the analysis of
      clinical characteristics of AAV patients, as to provide the basis for early
      diagnosis and treatment, and reduction of mortality and also improvement of
      prognosis. Methods: A retrospective study was conducted in patients with AAV
      which were admitted to this hospital from November 2003 to February 2017, by the
      contrasts of the similarities and differences of clinical characteristics between
      the death group and non-death group, for explore the risk factors of death.
      Results: (1) A total of 66 patients with AAV were included in this study, in
      which 20 were died (male/female was 12/8), and 46 were still alive, with a total
      mortality rate of 30.3%.(2)The average age of disease onset in the death group
      was (67+/-13) years, which was significantly higher than that of the control
      group (55+/-18, P=0.009). (3)The mean value of vasculitis damage index (VDI) in
      the death group was (6.4+/-2.5), which was significantly higher than that in the
      non-death group (4.4+/-2.5, P=0.006). (4)As to multiple organs involvements among
      the heart, lung, kidney, gastrointestinal tract, central nervous system and other
      organs, the proportion of three or more organs involvement in the death group was
      85% (17/20), which was significantly higher than that in the control group
      47.8%(22/46), P=0.004 8.The incidence of heart murmurs, recent premature beats,
      aortic insufficiency, chronic heart failure/cardiomyopathy, and massive
      hemoptysis were significantly higher than those in the control group (P<0.05).
      (5) The incidence of infection in the death group (55%) was significantly higher
      than that in the control group (28.3%, P=0.038). Conclusion: An onset age of more
      than 65, multiple organs involvement, especially the occurrence of massive
      hemoptysis, heart valve diseases, heart failure and other cardiovascular
      involvements, increased VDI and combination of infections are the risk factors of
      death in AAV patients.

PMID- 29179280
TI  - [Prognostic value of right ventricular Tei index and cardiac markers in sepsis].
AB  - Objective: To investigate the risk factors of death in patients with sepsis.
      Methods: From August 2014 to August 2016, 58 patients suffering sepsis in
      intensive care unit (ICU) of the People's Liberation Army 105 Hospital were
      prospectively analyzed.All patients were divided into survival group (n=39) and
      death group (n=19). The patients' gender, age, past medical history, acute
      physiology and chronic health system II(APACHE II), Sequential organ failure
      assessment(SOFA) score, B-type natriuretic peptide, lactate, procalcitonin, left
      ventricle EF%, right ventricle Tei index were measured within 24 h after
      admission in ICU.Logistic regression analysis was used to evaluate the risk
      factors of death in septic patients.the hospital mortality of sepsis was assessed
      by receiver operating character (ROC) curves. Results: The hospital mortality
      rate of sepsis was 32.8% (19/58). Logistic regression analysis showed that SOFA
      score [OR=2.34, 95%CI: 1.069-5.258, P<0.01], cTnI[OR=1.21, 95%CI: 1.017-1.437,
      P=0.032], Tei index[OR=1.56, 95%CI: 1.082-2.263, P=0.017]. The APACHEII, SOFA
      score, lactic acid, cTnI, Tei index and cTnI combined with Tei index predicted
      the hospital mortality of sepsis with the area under ROC curve (AUC) of 0.821,
      0.848, 0.790, 0.756, 0.962, 0.982, respectively. Conclusion: Tei index and cTnI
      may be the independent risk factors of sepsis in patients with sepsis, and the
      incidence of major adverse cardiac events was high.

PMID- 29179281
TI  - [Effects of different computed high b-values on diffusion weighted imaging scores
      in Prostate Imaging Reporting and Data System version 2 of prostate cancer in
      peripheral zone].
AB  - Objective: To determine the effects of different computed high b-value on
      diffusion weighted imaging (DWI) scores in Prostate Imaging Reporting and Data
      System version 2 (PI-RADS v2) of prostate cancer in peripheral zone. Methods: A
      retrospective study of 104 cases of prostate cancer in peripheral zone was
      conducted, all of the patients were histopathologically confirmed by transrectal
      ultrasound guided saturation biopsy or radical prostatectomy in Tongji Hospital
      of Tongji University from January 2012 to December 2015.All MRI imaging
      examinations were performed by using a 3.0T Siemens Verio MRI scanner.The imaging
      protocol consisted of high-resolution axial and sagittal T(2) weighted imaging
      (T(2)WI), axial acquired diffusion weighted imaging (aDWI) with b=0, 50, 1 000
      s/mm(2) and dynamic contrast-enhanced (DCE) scans.Computed diffusion weighted
      imaging (cDWI) images with b=1 000, 1 400, 2 000 s/mm(2) were processed by
      Matlab.These three groups of cDWI images were analyzed according to the PI-RADS
      v2 criteria, and signal intensity of ratio (SIR) of lesions were analyzed by
      independent t test and one-way ANOVA in each group. Results: The numbers of cases
      with a DWI score of 2 and 5 were similar among three groups.Nine cases (33.3%) in
      all 27 cases with a DWI score of 3 on b=1 000 s/mm(2) upgraded to score 4 when b
      value rose to 1 400 and 2 000 s/mm(2).The ratios of SIR of lesions in cases
      upgraded from DWI score 3 to 4 to those unchanged cases on b=1 400 and 2 000
      s/mm(2) were 1.86+/-0.21 to 1.61+/-0.27 and 2.18+/-0.26 to 1.75+/-0.30,
      respectively (t=2.486, t=3.671, both P<0.05). In these 9 cases who upgraded to
      DWI score 4, SIRs of the lesion were significantly different between groups when
      b=1 000, 1 400 and 2 000 s/mm(2) (F=10.907, 33.768, 8.043, all P<0.05), and their
      SIRs increased with the rising of b-value. Conclusions: The computed high b-value
      (b>=1 400 s/mm(2)) mainly affects cases with a DWI score of 3, but DWI scores
      would not change neither in b=1 400 s/mm(2) nor in 2 000 s/mm(2) cases. For DWI
      score in PI-RADS v2 of prostate cancer in peripheral zone, b=1 400 s/mm(2) is
      probably of more scoring value than b=1 000 or 2 000 s/mm(2).

PMID- 29179282
TI  - [Clinical value of spectral CT imaging in preoperative evaluation of pathological
      grading of esophageal squamous cell carcinoma].
AB  - Objective: To investigate the value of spectral computed tomography quantitative
      parameters in the assessment of pathological grade of esophageal squamous cell
      carcinoma before operation. Methods: The imaging findings of 52 patients with
      confirmed esophageal squamous cell carcinoma by surgery and pathology were
      prospectively analyzed in Henan Provincial People's Hospital from June 2016 to
      May 2017.There were 43 males and 9 females, aged 49-76 years, with an average age
      of (66+/-8) years.All the patients were divided into three groups based on the
      pathological finding: well-differentiated group (n=12), moderately-differentiated
      group (n=20), poorly-differentiated group (n=20). All the patients received chest
      plain scan and double phase enhanced scan of gemstone spectral computed
      tomography.The enhancement attenuation (HU), the average of the slope of the
      spectral Hounsfield Unit curve (lambda(HU)), normalized iodine concentration
      (NIC), normalized effective atomic number (Z(eff-a)) were measured and
      calculated.The difference in HU, lambda(HU), NIC, Z(eff-a) among different grades
      were statistically analyzed.The receiver operating characteristic (ROC) curve was
      used to evaluate the diagnostic efficiency of single and combined parameters in
      the differentiation of poorly-differentiated and well-moderately differentiated
      esophageal squamous cell carcinoma. Results: There were significant differences
      in HU, lambda(HU), NIC, Z(eff-a) among different pathological grading of the
      esophageal squamous cell carcinoma in arterial phase and venous phase (F=4.496
      9.056, H=23.204, 20.724, all P<0.05). The best single parameter to differentiate
      poorly-differentiated from well-moderately differentiated esophageal squamous
      cell carcinoma was NIC in arterial phase with areas under the ROC curve (AUC),
      the cutoff value, sensitivity, specificity, accuracy of 0.860, 0.197, 65.0%,
      96.9%, 84.6%, respectively; the best combination of parameters was HU+ NIC+
      lambda(HU) in arterial phase with AUC, the threshold of predicted probability,
      sensitivity, specificity, accuracy of 0.913, 0.380, 85.0%, 81.3%, 82.7%,
      respectively. Conclusion: Gemstone spectral imaging quantitative parameters can
      be used to evaluate the pathological grading of esophageal squamous cell
      carcinoma, the NIC and HU+ NIC+ lambda(HU) in arterial phase have the highest
      differential diagnostic efficiency.

PMID- 29179283
TI  - [A survey of willingness about genetic counseling and tests in patients of
      epithelial ovarian cancer].
AB  - Objective: To analyze patients' tendency towards genetics counseling and tests
      based on a prospective cohort study on hereditary ovarian cancer. Methods: From
      February 2017 to June 2017, among 220 cases of epithelial ovarian cancer in
      Peking Union Medical College Hospital, we collected epidemiological, pathological
      and tendency towards genetics counseling and tests via medical records and
      questionnaire.All patients would get education about hereditary ovarian cancer by
      pamphlets and WeChat.If they would receive further counseling, a face to face
      interview and tests will be given. Results: Among all 220 patients, 10 (4.5%)
      denied further counseling.For 210 patients receiving genetic counseling, 170
      (81%) accepted genetic tests.In multivariate analysis, risk factors relevant to
      acceptance of genetic tests included: being charged by physicians of gynecologic
      oncology for diagnosis and treatment, receiving counseling in genetic counseling
      clinics, and having family history of breast cancer.For patients denying genetic
      tests, there were many subjective reasons, among which, "still not understanding
      genetic tests" (25%) and "unable bear following expensive targeting medicine" .
      Conclusions: High proportion patients of epithelial ovarian cancer would accept
      genetic counseling and tests.Genetic counseling clinics for gynecologic oncology
      would further improve genetic tests for patients.

PMID- 29179284
TI  - [Analysis of correlation between spinal nerve high tension and disc degeneration
      in 100 cases].
AB  - Objective: To explore the correlation between the spinal nerve high tension and
      lumbar disc degeneration, the pathogenesis of hanging intervertebral disc
      degeneration. Methods: From June 2016 to June , a retrospective analysis 2017 of
      100 cases of lumbar spinal stenosis were included in Department of Spine Surgery,
      Changzheng Hospital, the Second Military Medical University. They were divided
      into experimental group (50 cases, nerve high tension group) and control group
      (50 cases, nervous tension in the normal group) according to preoperative lumbar
      MRI of cauda equina syndrome and settlement of intraoperative detecting nerve
      tension. The Pfirrmann grade was used to evaluate degree of lumbar (L3/4-L5/S1)
      disc degeneration.The correlation between spinal nerve tension and lumbar disc
      degeneration was analyzed, and the severity of experimental group and control
      group on lumbar disc degeneration was compared. Results: There was no significant
      difference in the age and sex ratio between the two groups (P>0.05). The
      Pfirrmann score of the experimental group was L3/4 (4.74+/-1.6) grade, L4/5
      (5.32+/-1.33) grade, L5/S1 (5.54+/-1.13) grade; the control group Pfirrmann score
      was L3/4 (3.5+/-1.16) grade, L4/5 (4.12+/-0.9) grade, and L5/S1 (4.1+/-0.97)
      grade.The severity of intervertebral disc degeneration in experimental group was
      higher than that in control group, with statistical significance (P<0.05). There
      was a correlation between lumbar disc degeneration and nerve tension in L3/4,
      L4/5 and L5/S1, and the correlation trend was L5/S1> L4/5> L3/4. Conclusion:
      There is a correlation between lumbar disc degeneration and spinal nerve high
      tension.A new pathogenesis of hanging intervertebral disc degeneration that the
      degeneration of lumbar disc is a compensatory mechanism in order to alleviate the
      axial stretch injury is put forward.

PMID- 29179285
TI  - [Efficacy of 3D print guide technique in one stage posterior approach for the
      treatment of cervical and thoracic tuberculosis with kyphosis].
AB  - Objective: To investigate the application of 3D printing technology in the
      treatment of patients with cervical kyphosis and paraplegia in different segments
      of the cervical spine after one-stage debridement, bone graft fusion and pedicle
      screw fixation. Methods: From January 2008 to January 2017, a total of 31
      patients with thoracolumbar tuberculosis were treated in the Department of
      Orthopaedics, the Xinjiang Uygur Autonomous Region people's Hospital.Lesions of
      the thoracic spine (T1-T4) in 8 cases, (C5-C7) in 10 cases, cervical and thoracic
      segment in 13 cases, involving a total of 2 cases of vertebral body in 7 cases, 3
      cases of vertebral body in 14 cases, 4 cases of vertebral body. 3D printing group
      (group A) 12 cases, non 3D printing group (group B) of 19 cases.All cases were
      treated with a posterior approach to the treatment of the cervical spinal cord
      around the spinal cord.After taking regular anti tuberculosis drugs in 6-12
      months, follow-up observation of correction of kyphosis and paraplegia recovery,
      blood sedimentation rate (ESR), C-reactive protein (CRP) changes. Results: All
      cases were followed up for at least 6 months. Twelve patients were treated with
      3D printing technique before operation, and the operation was performed according
      to the preoperative plan.The diameter and length of pedicle screws, the direction
      of insertion, and the distance between the insertion point and the posterior
      midline of the pedicle screw were similar to those in the 3D.Three days after the
      operation, the effect of fracture reduction was satisfactory, and the position of
      pedicle screws was good.After 6 months of follow-up, the X-ray showed that the
      pedicle screws were in good position, and there was no loosening and fracture.All
      the patients were healed, and there was no segmental instability.3D printing
      group during surgery bleeding, operation time, postoperative drainage volume,
      compared with the non 3D print group of surgical results, 3D printing group
      significantly reduce the surgical trauma[(131+/-18) min vs (162+/-23), P<0.01;
      (528+/-34) ml vs (615+/-41) ml, P<0.01; (257+/-46) vs (327+/-56), P<0.01; (not
      grouping, before after operation), (64+/-42) mm/1 h vs (6+/-7) mm/1 h, P<0.01;
      CRP (not packet): (72+/-41) MUg/L, (13+/-6) mm/1 h, P<0.01]. There was
      significant difference between two groups.The JOA scores of patients in the 3D
      group were better than those in the non 3D group after the operation in 1, 2 week
      and in 1, 3, and month.There was no significant difference between the two groups
      after the operation.Two groups of patients before and after correction of Cobb
      angle were satisfied, and no significant difference between the two groups.Cobb
      lost an average of 1 degrees angle correction.The spinal tuberculosis in this
      group were cured without serious complications. Conclusions: According to the
      cervical and thoracic tuberculous kyphosis and paraplegia severity, choose a
      posterior surgery can achieve effective cure, feasible thorough debridement with
      fixed spinal stability before and after the party obtained bone fusion and
      deformity correction in 3D technology to increase the accuracy and safety of
      operation, and can be provide more detailed preoperative, intuitive, three
      dimensional, realistic personalized operation scheme.It can reduce the operation
      trauma, and achieve rapid recovery after operation.

PMID- 29179286
TI  - [Decolorization of skin and hair-derived melanin by three ligninolytic enzymes].
AB  - Objective: To compare the decolorization efficiency of lignin peroxidase (LiP),
      manganese peroxidase (MnP) and laccase on eumelanin and pheomelanin, and to
      investigate the effect of topical administration of LiP solution on
      hyperpigmented guinea pigs skin induced by 308 nm excimer light. Methods:
      Pheomelanin-enriched specimens were prepared from human hair and cutaneous
      melanoma tissue using alkaline lysis method.Synthetic eumelanin was purchased
      from a commercial supplier.The same amount (0.02%) of melanin was incubated with
      the equal enzyme activity (0.2 U/ml) of ligninolytic enzymes for 3 h
      respectively.The absorbance at 475 nm (A(475)) in the enzyme-catalyzed solution
      was measured using ELISA microplate reader.The experimental hyperpigmentation
      model was established in the dorsal skin of brownish guinea pigs using 308 nm
      excimer light radiation.LiP and heat-inactivated LiP solution were topically
      applied at each site.Meanwhile, 3% hydroquinone and vehicle cream were used as
      control.The skin color (L value) was recorded using a CR-10 Minolta
      chromameter.Corneocytes were collected using adhesive taping method.The amount
      and distribution of melanin in the corneocytes and skin tissues was visualized by
      Fontana-Masson staining. Results: All three ligninolytic enzymes showed various
      degree of eumelanin and pheomelanin decolorization activity.The decolorization
      activity of LiP, MnP and laccase was 40%-70%, 22%-42% and 9%-21%,
      respectively.The similar lightening was shown in the skin treated with LiP
      solution and 3% hydroquinone.The amount of melanin granules in the corneocytes
      was 199+/-11 by LiP, which was less than that in untreated control (923+/-12) and
      heat-inactive control (989+/-13). The amount of melanin was decreased in the
      whole epidermis treated with hydroquinone, the epidermis thickness was increased
      as well. In contrast, melanin of LiP group was decreased only in the superficial
      epidermis, the epidermis thickness seemed to be normal. Conclusion: LiP exerts a
      potent decolorization activity for hair- or skin-derived pheomelanin as well as
      eumelanin.It remains to be further investigated whether LiP serves as a
      substitute for hydroquinone in skin lightening products.

PMID- 29179287
TI  - Interest of Anorectal Manometry During Long-term Follow-up of Patients Operated
      on for Hirschsprung's Disease.
AB  - Background/Aims: Although many advances in the management of Hirschsprung's
      disease have recently been achieved, postoperative outcomes of these patients
      remain difficult in a non-negligible number of cases. Therefore, this study aims
      at investigating characteristics of anorectal manometry and its relationship with
      postoperative outcomes during long-term follow-up in Hirschsprung patients.
      Methods: Patients over 4 years of age operated on for Hirschsprung's disease were
      interviewed to complete detailed questionnaires on bowel function. The patients
      who consented to undergo an anorectal manometry during follow-up were enrolled in
      this study. We investigated their clinical characteristics, manometric findings,
      and their postoperative bowel function. Results: Nineteen patients out of 53
      patients (35.8%) were enrolled, 68.4% who were male. Mean age of patients at
      manometry was 11.3 +/- 6.3 years. Twelve out of 19 patients (63.2%) were
      incontinent. The mean anal resting pressures of incontinent patients were
      significantly lower than continent patients (47 +/- 12 mmHg versus 63 +/- 11
      mmHg, P < 0.05, t test). Due to neurological impairment, only 11 patients (57.9%)
      were able to perform a complete manometry. A dyssynergic defecation was found in
      4 patients during strain tests. Maximum tolerated volume of the incontinent
      patients was significantly lower than that of the continent patients (97 +/- 67
      mL versus 181 +/- 74 mL, P < 0.05, t test). Conclusion: Anorectal manometry is an
      objective method providing useful information that could guide a more adapted
      management in patients with defecation disorders after Hirschsprung's disease
      operation.

PMID- 29179288
TI  - Public Spending on Health Service and Policy Research in Canada, the United
      Kingdom, and the United States: A Modest Proposal.
AB  - Health services and policy research (HSPR) represent a multidisciplinary field
      which integrates knowledge from health economics, health policy, health
      technology assessment, epidemiology, political science among other fields, to
      evaluate decisions in health service delivery. Health service decisions are
      informed by evidence at the clinical, organizational, and policy level, levels
      with distinct, managerial drivers. HSPR has an evolving discourse spanning
      knowledge translation, linkage and exchange between research and decision-maker
      partners and more recently, implementation science and learning health systems.
      Local context is important for HSPR and is important in advancing health reform
      practice. The amounts and configuration of national investment in this field
      remain important considerations which reflect priority investment areas. The
      priorities set within this field or research may have greater or lesser effects
      and promise with respect to modernizing health services in pursuit of better
      value and better population outcomes. Within Canada an asset map for HSPR was
      published by the national HSPR research institute. Having estimated publicly
      funded research spending in Canada, we sought identify best available comparable
      estimates from the United States and the United Kingdom. Investments from
      industry and charitable organizations were not included in these numbers. This
      commentary explores spending by the United States, Canada, and the United Kingdom
      on HSPR as a fraction of total public spending on health and the importance of
      these respective investments in advancing health service performance. Proposals
      are offered on the merits of common nomenclature and accounting for areas of
      investigation in pursuit of some comparable way of assessing priority HSPR
      investments and suggestions for earmarking such investments to total investment
      in health services spending.

PMID- 29179289
TI  - Informal Patient Payments and Bought and Brought Goods in the Western Balkans - A
      Scoping Review.
AB  - BACKGROUND: Informal patient payments for healthcare are common in the Western
      Balkans, negatively affecting public health and healthcare. AIM: To identify
      literature from the Western Balkans on what is known about informal patient
      payments and bought and brought goods, to examine their effects on healthcare and
      to determine what actions can be taken to tackle these payments. METHODS: After
      conducting a scoping review that involved searching websites and databases and
      filtering with eligibility criteria and quality assessment tools, 24 relevant
      studies were revealed. The data were synthesized using a narrative approach that
      identified key concepts, types of evidence, and research gaps. RESULTS: The
      number of studies of informal patient payments increased between 2002 and 2015,
      but evidence regarding the issues of concern is scattered across various
      countries. Research has reported incidents of informal patient payments on a wide
      scale and has described various patterns and characteristics of these payments.
      Although these payments have typically been small - particularly to providers in
      common areas of specialized medicine - evidence regarding bought and brought
      goods remains limited, indicating that such practices are likely even more
      common, of greater magnitude and perhaps more problematic than informal patient
      payments. Only scant research has examined the measures that are used to tackle
      informal patient payments. The evidence indicates that legalizing informal
      patient payments, introducing performance-based payment systems, strengthening
      reporting, changing mentalities and involving the media and the European Union
      (EU) or religious organizations in anti-corruption campaigns are understood as
      some of the possible remedies that might help reduce informal patient payments.
      CONCLUSION: Despite comprehensive evidence regarding informal patient payments,
      data remain scattered and contradictory, implying that informal patient payments
      are a complex phenomenon. Additionally, the data on bought and brought goods
      illustrate that not much is known about this matter. Although informal patient
      payments have been studied and described in several settings, there is still
      little research on the effectiveness of such strategies in the Western Balkans
      context.

PMID- 29179290
TI  - Contextualizing Obesity and Diabetes Policy: Exploring a Nested Statistical and
      Constructivist Approach at the Cross-National and Subnational Government Level in
      the United States and Brazil.
AB  - BACKGROUND: This article conducts a comparative national and subnational
      government analysis of the political, economic, and ideational constructivist
      contextual factors facilitating the adoption of obesity and diabetes policy.
      METHODS: We adopt a nested analytical approach to policy analysis, which combines
      cross-national statistical analysis with subnational case study comparisons to
      examine theoretical prepositions and discover alternative contextual factors;
      this was combined with an ideational constructivist approach to policy-making.
      RESULTS: Contrary to the existing literature, we found that with the exception of
      cross-national statistical differences in access to healthcare infrastructural
      resources, the growing burden of obesity and diabetes, rising healthcare costs
      and increased citizens' knowledge had no predictive affect on the adoption of
      obesity and diabetes policy. We then turned to a subnational comparative analysis
      of the states of Mississippi in the United States and Rio Grande do Norte in
      Brazil to further assess the importance of infrastructural resources, at two
      units of analysis: the state governments versus rural municipal governments.
      Qualitative evidence suggests that differences in subnational healthcare
      infrastructural resources were insufficient for explaining policy reform
      processes, highlighting instead other potentially important factors, such as
      state-civil societal relationships and policy diffusion in Mississippi, federal
      policy intervention in Rio Grande do Norte, and politicians' social construction
      of obesity and the resulting differences in policy roles assigned to the central
      government. CONCLUSION: We conclude by underscoring the complexity of subnational
      policy responses to obesity and diabetes, the importance of combining resource
      and constructivist analysis for better understanding the context of policy
      reform, while underscoring the potential lessons that the United States can learn
      from Brazil.

PMID- 29179291
TI  - Lost in Translation: Piloting a Novel Framework to Assess the Challenges in
      Translating Scientific Uncertainty From Empirical Findings to WHO Policy
      Statements.
AB  - BACKGROUND: Calls for evidence-informed public health policy, with implicit
      promises of greater program effectiveness, have intensified recently. The methods
      to produce such policies are not self-evident, requiring a conciliation of values
      and norms between policy-makers and evidence producers. In particular, the
      translation of uncertainty from empirical research findings, particularly issues
      of statistical variability and generalizability, is a persistent challenge
      because of the incremental nature of research and the iterative cycle of
      advancing knowledge and implementation. This paper aims to assess how the concept
      of uncertainty is considered and acknowledged in World Health Organization (WHO)
      policy recommendations and guidelines. METHODS: We selected four WHO policy
      statements published between 2008-2013 regarding maternal and child nutrient
      supplementation, infant feeding, heat action plans, and malaria control to
      represent topics with a spectrum of available evidence bases. Each of these four
      statements was analyzed using a novel framework to assess the treatment of
      statistical variability and generalizability. RESULTS: WHO currently provides
      substantial guidance on addressing statistical variability through GRADE (Grading
      of Recommendations Assessment, Development, and Evaluation) ratings for precision
      and consistency in their guideline documents. Accordingly, our analysis showed
      that policy-informing questions were addressed by systematic reviews and
      representations of statistical variability (eg, with numeric confidence
      intervals). In contrast, the presentation of contextual or "background" evidence
      regarding etiology or disease burden showed little consideration for this
      variability. Moreover, generalizability or "indirectness" was uniformly
      neglected, with little explicit consideration of study settings or subgroups.
      CONCLUSION: In this paper, we found that non-uniform treatment of statistical
      variability and generalizability factors that may contribute to uncertainty
      regarding recommendations were neglected, including the state of evidence
      informing background questions (prevalence, mechanisms, or burden or
      distributions of health problems) and little assessment of generalizability,
      alternate interventions, and additional outcomes not captured by systematic
      review. These other factors often form a basis for providing policy
      recommendations, particularly in the absence of a strong evidence base for
      intervention effects. Consequently, they should also be subject to stringent and
      systematic evaluation criteria. We suggest that more effort is needed to
      systematically acknowledge (1) when evidence is missing, conflicting, or
      equivocal, (2) what normative considerations were also employed, and (3) how
      additional evidence may be accrued.

PMID- 29179292
TI  - Bringing Value-Based Perspectives to Care: Including Patient and Family Members
      in Decision-Making Processes.
AB  - BACKGROUND: Recent evidence shows that patient engagement is an important
      strategy in achieving a high performing healthcare system. While there is
      considerable evidence of implementation initiatives in direct care context, there
      is limited investigation of implementation initiatives in decision-making context
      as it relates to program planning, service delivery and developing policies.
      Research has also shown a gap in consistent application of system-level
      strategies that can effectively translate organizational policies around patient
      and family engagement into practice. METHODS: The broad objective of this
      initiative was to develop a system-level implementation strategy to include
      patient and family advisors (PFAs) at decision-making points in primary
      healthcare (PHC) based on wellestablished evidence and literature. In this
      opportunity sponsored by the Canadian Foundation for Healthcare Improvement
      (CFHI) a co-design methodology, also well-established was applied in identifying
      and developing a suitable implementation strategy to engage PFAs as members of
      quality teams in PHC. Diabetes management centres (DMCs) was selected as the
      pilot site to develop the strategy. Key steps in the process included review of
      evidence, review of the current state in PHC through engagement of key
      stakeholders and a co-design approach. RESULTS: The project team included a
      diverse representation of members from the PHC system including patient advisors,
      DMC team members, system leads, providers, Public Engagement team members and
      CFHI improvement coaches. Key outcomes of this 18-month long initiative included
      development of a working definition of patient and family engagement, development
      of a Patient and Family Engagement Resource Guide and evaluation of the resource
      guide. CONCLUSION: This novel initiative provided us an opportunity to develop a
      supportive system-wide implementation plan and a strategy to include PFAs in
      decision-making processes in PHC. The well-established co-design methodology
      further allowed us to include value-based (customer driven quality and experience
      of care) perspectives of several important stakeholders including patient
      advisors. The next step will be to implement the strategy within DMCs, spread the
      strategy PHC, both locally and provincially with a focus on sustainability.

PMID- 29179293
TI  - "Enemies of the People?" Public Health in the Era of Populist Politics Comment on
      "The Rise of Post-truth Populism in Pluralist Liberal Democracies: Challenges for
      Health Policy".
AB  - In this commentary, we review the growth of populist politics, associated with
      exploitation of what has been termed fake news. We explore how certain words have
      been used in similar contexts historically, in particular the term "enemy of the
      people," especially with regard to public health. We then set out 6 principles
      for public health professionals faced with these situations. First, using their
      epidemiological skills, they can provide insights into the reasons underlying the
      growth of populist politics. Second using their expertise in modelling and health
      impact assessment, they can anticipate and warn about the consequences of
      populist policies. Third, they can support the institutions that are necessary
      for effective public health. Fourth they can reclaim the narrative, rejecting
      hatred and division, to promote social solidarity. Fifth, they can support fact
      checking and the use of evidence. Finally, they should always remember the
      lessons of history, and in particular, the way that public health has, on
      occasions, collaborated with totalitarian and genocidal regimes.

PMID- 29179294
TI  - "Stop, You're Killing us!" An Alternative Take on Populism and Public Health
      Comment on "The Rise of Post-truth Populism in Pluralist Liberal Democracies:
      Challenges for Health Policy".
AB  - Ewen Speed and Russell Mannion correctly identify several contours of the
      challenges for health policy in what it is useful to think of as a post
      democratic era. I argue that the problem for public health is not populism per
      se, but rather the distinctive populism of the right coupled with the failure of
      the left to develop compelling counternarratives. Further, defences of 'science'
      must be tempered by recognition of the unavoidably political dimensions of the
      (mis)use of scientific findings in public policy.

PMID- 29179295
TI  - Passed the Age of Puberty: Organizational Networks as a Way to Get Things Done in
      the Health Field Comment on "Evaluating Global Health Partnerships: A Case Study
      of a Gavi HPV Vaccine Application Process in Uganda".
AB  - In this commentary I will demonstrate that the case study of Uganda's Human
      papilloma virus (HPV) vaccine application partnership provides an excellent
      example of widening our lens by evaluating the successful HPV vaccine coverage
      from a network-centric perspective. That implies that the organizational network
      is seen as the locus of production and that network theories become indispensable
      to analyze the situation at hand. The case study is, as said, an excellent
      example of how this can be done and my comments have to be read as an endorsement
      and a broadening of the discussion of what Carol Kamya and colleagues have
      presented. It is demonstrated that an organizational network approach can be
      considered a serious and mature way in understanding public health issues.

PMID- 29179296
TI  - Define and Conquer: How Semantics Foster Progress; A Response to Recent
      Commentaries.

PMID- 29179297
TI  - Family Planning as a Possible Measure to Alleviate Poverty in the Philippines -
      Beyond Sociocultural Norms and Pervasive Opposition.

PMID- 29179299
TI  - The American Academy of Pediatric Dentistry Strategic Plan 2020.

PMID- 29179298
TI  - Overview.

PMID- 29179301
TI  - Definition of Dental Home.

PMID- 29179302
TI  - Definition of Dental Neglect.

PMID- 29179303
TI  - Definition of Dental Disability.

PMID- 29179305
TI  - Definition of Special Health Care Needs.

PMID- 29179304
TI  - Definition of Medically-Necessary Care.

PMID- 29179306
TI  - Policy on Medically-Necessary Care.

PMID- 29179307
TI  - Policy on Social Determinants of Children's Oral Health and Health Disparities.

PMID- 29179308
TI  - Review Council Policy on Oral Health Care Programs for Infants, Children, and
      Adolescents.

PMID- 29179309
TI  - Policy on the Dental Home.

PMID- 29179310
TI  - Policy on Workforce Issues and Delivery of Oral Health Care Services in a Dental
      Home.

PMID- 29179311
TI  - Policy on Child Identification Programs.

PMID- 29179312
TI  - Policy on Oral Health in Child Care Centers.

PMID- 29179313
TI  - Policy on Mandatory School-entrance Oral Health Examinations.

PMID- 29179314
TI  - Policy on School Absences for Dental Appointments.

PMID- 29179315
TI  - Policy on Emergency Oral Care for Infants, Children, Adolescents, and Individuals
      with Special Health Care Needs.

PMID- 29179316
TI  - Policy on the Role of Dental Prophylaxis in Pediatric Dentistry.

PMID- 29179317
TI  - Policy on Use of Fluoride.

PMID- 29179318
TI  - Policy on the Use of Silver Diamine Fluoride for Pediatric Dental Patients.

PMID- 29179319
TI  - Policy on the Use of Xylitol.

PMID- 29179320
TI  - Policy on Interim Therapeutic Restorations (ITR).

PMID- 29179321
TI  - Policy on Early Childhood Caries (ECC): Classifications, Consequences, and
      Preventive Strategies.

PMID- 29179322
TI  - Policy on Early Childhood Caries (ECC): Unique Challenges and Treatment Options.

PMID- 29179323
TI  - Policy on Dietary Recommendations for Infants, Children, and Adolescents.

PMID- 29179324
TI  - Policy on Snacks and Beverages Sold in Schools.

PMID- 29179325
TI  - Policy on Tobacco Use.

PMID- 29179326
TI  - Policy on Electronic Cigarettes.

PMID- 29179327
TI  - Policy on Substance Abuse in Adolescent Patients.

PMID- 29179328
TI  - Policy on Human Papilloma Virus Vaccinations.

PMID- 29179329
TI  - Policy on Intraoral/Perioral Piercing and Oral Jewelry/Accessories.

PMID- 29179330
TI  - Policy on Prevention of Sports-related Orofacial Injuries.

PMID- 29179331
TI  - Policy on the Use of Dental Bleaching for Child and Adolescent Patients.

PMID- 29179332
TI  - Policy on the Use of Lasers for Pediatric Dental Patients.

PMID- 29179333
TI  - Policy on Obstructive Sleep Apnea.

PMID- 29179334
TI  - Policy on Acute Pediatric Dental Pain Management.

PMID- 29179335
TI  - Policy on Minimizing Occupational Health Hazards Associated with Nitrous Oxide.

PMID- 29179336
TI  - Policy on Hospitalization and Operating Room Access for Oral Care of Infants,
      Children, Adolescents, and Individuals with Special Health Care Needs.

PMID- 29179337
TI  - Policy on Hospital Staff Membership.

PMID- 29179338
TI  - Policy on Model Dental Benefits for Infants, Children, Adolescents, and
      Individuals with Special Health Care Needs.

PMID- 29179339
TI  - Policy on Third-party Reimbursement for Management of Patients with Special
      Health Care Needs.

PMID- 29179340
TI  - Policy on Third-party Reimbursement of Medical Fees Related to Sedation/General
      Anesthesia for Delivery of Oral Health Care Services.

PMID- 29179341
TI  - Policy on Third-party Reimbursement for Oral Health Care Services Related to
      Congenital and Acquired Orofacial Anomalies.

PMID- 29179343
TI  - Policy on Third-Party Fee Capping of Non-Covered Services.

PMID- 29179342
TI  - Policy on Third-party Reimbursement of Fees Related to Dental Sealants.

PMID- 29179344
TI  - Policy on Third-Party Payor Audits, Abuse, and Fraud.

PMID- 29179345
TI  - Policy on the Role of Pediatric Dentists as Both Primary and Specialty Care
      Providers.

PMID- 29179346
TI  - Policy on Transitioning from a Pediatric-centered to an Adult-centered Dental
      Home for Individuals with Special Health Care Needs.

PMID- 29179347
TI  - Policy on Patient Safety.

PMID- 29179348
TI  - Policy on the Ethical Responsibilities in the Oral Health Care Management of
      Infants, Children, Adolescents, and Individuals with Special Health Care Needs.

PMID- 29179349
TI  - Policy on Second Opinion for Pediatric Oral Health Care.

PMID- 29179350
TI  - Policy on a Patient's Bill of Rights and Responsibilities.

PMID- 29179351
TI  - Policy on Using Harvested Dental Stem Cells.

PMID- 29179352
TI  - Policy on Infection Control.

PMID- 29179353
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- 29179354
TI  - Use of Pit-and-Fissure Sealants.
AB  - BACKGROUND: This article presents evidence-based clinical recommendations for the
      use of pit-and-fissure sealants on the occlusal surfaces of primary and permanent
      molars in children and adolescents. A guideline panel convened by the American
      Dental Association (ADA) Council on Scientific Affairs and the American Academy
      of Pediatric Dentistry conducted a systematic review and formulated
      recommendations to address clinical questions in relation to the efficacy,
      retention, and potential side effects of sealants to prevent dental caries; their
      efficacy compared with fluoride varnishes; and a head-to-head comparison of the
      different types of sealant material used to prevent caries on pits-and-fissures
      of occlusal surfaces. TYPES OF STUDIES REVIEWED: This is an update of the ADA
      2008 recommendations on the use of pit-and-fissure sealants on the occlusal
      surfaces of primary and permanent molars. The authors conducted a systematic
      search in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and
      other sources to identify randomized controlled trials reporting on the effect of
      sealants (available on the U.S. market) when applied to the occlusal surfaces of
      primary and permanent molars. The authors used the Grading of Recommendations
      Assessment, Development, and Evaluation approach to assess the quality of the
      evidence and to move from the evidence to the decisions. RESULTS: The guideline
      panel formulated 3 main recommendations. They concluded that sealants are
      effective in preventing and arresting pit-and-fissure occlusal carious lesions of
      primary and permanent molars in children and adolescents compared with the nonuse
      of sealants or use of fluoride varnishes. They also concluded that sealants could
      minimize the progression of non-cavitated occlusal carious lesions (also referred
      to as initial lesions) that receive a sealant. Finally, based on the available
      limited evidence, the panel was unable to provide specific recommendations on the
      relative merits of 1 type of sealant material over the others. Conclusions and
      practical implications: These recommendations are designed to inform
      practitioners during the clinical decision-making process in relation to the
      prevention of occlusal carious lesions in children and adolescents. Clinicians
      are encouraged to discuss the information in this guideline with patients or the
      parents of patients. The authors recommend that clinicians re-orient their
      efforts toward increasing the use of sealants on the occlusal surfaces of primary
      and permanent molars in children and adolescents.

PMID- 29179355
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- 29179356
TI  - Periodicity of Examination, Preventive Dental Services, Anticipatory
      Guidance/Counseling, and Oral Treatment for Infants, Children, and Adolescents.

PMID- 29179357
TI  - Caries-risk Assessment and Management for Infants, Children, and Adolescents.

PMID- 29179358
TI  - Prescribing Dental Radiographs for Infants, Children, Adolescents, and
      Individuals with Special Health Care Needs.

PMID- 29179359
TI  - Perinatal and Infant Oral Health Care.

PMID- 29179360
TI  - Adolescent Oral Health Care.

PMID- 29179361
TI  - Oral Health Care for the Pregnant Adolescent.

PMID- 29179362
TI  - Management of Dental Patients with Special Health Care Needs.

PMID- 29179363
TI  - Oral and Dental Aspects of Child Abuse and Neglect.
AB  - In all 50 states, health care providers (including dentists) are mandated to
      report suspected cases of abuse and neglect to social service or law enforcement
      agencies. The purpose of this report is to review the oral and dental aspects of
      physical and sexual abuse and dental neglect in children and the role of
      pediatric care providers and dental providers in evaluating such conditions. This
      report addresses the evaluation of bite marks as well as perioral and intraoral
      injuries, infections, and diseases that may raise suspicion for child abuse or
      neglect. Oral health issues can also be associated with bullying and are commonly
      seen in human trafficking victims. Some medical providers may receive less
      education pertaining to oral health and dental injury and disease and may not
      detect the mouth and gum findings that are related to abuse or neglect as readily
      as they detect those involving other areas of the body. Therefore, pediatric care
      providers and dental providers are encouraged to collaborate to increase the
      prevention, detection, and treatment of these conditions in children.

PMID- 29179364
TI  - Fluoride Therapy.

PMID- 29179365
TI  - Behavior Guidance for the Pediatric Dental Patient.

PMID- 29179366
TI  - Protective Stabilization for Pediatric Dental Patients.

PMID- 29179367
TI  - Use of Local Anesthesia for Pediatric Dental Patients.

PMID- 29179368
TI  - Use of Nitrous Oxide for Pediatric Dental Patients.

PMID- 29179369
TI  - Monitoring and Management of Pediatric Patients Before, During, and After
      Sedation for Diagnostic and Therapeutic Procedures: Update 2016.
AB  - The safe sedation of children for procedures requires a systematic approach that
      includes the following: no administration of sedating medication without the
      safety net of medical/dental supervision, careful presedation evaluation for
      underlying medical or surgical conditions that would place the child at increased
      risk from sedating medications, appropriate fasting for elective procedures and a
      balance between the depth of sedation and risk for those who are unable to fast
      because of the urgent nature of the procedure, a focused airway examination for
      large (kissing) tonsils or anatomic airway abnormalities that might increase
      thepotential for airway obstruction, a clear understanding of the medication's
      pharmacokinetic and pharmacodynamic effects and drug interactions, appropriate
      training and skills in airway management to allow rescue of the patient, age- and
      size-appropriate equipment for airway management and venous access, appropriate
      medications and reversal agents, sufficient numbers of staff to both carry out
      the procedure and monitor the patient, appropriate physiologic monitoring during
      and after the procedure, a properly equipped and staffed recovery area, recovery
      to the presedation level of consciousness before discharge from medical/dental
      supervision, and appropriate discharge instructions. This report was developed
      through a collaborative effort of the American Academy of Pediatrics and the
      American Academy of Pediatric Dentistry to offer pediatric providers updated
      information and guidance in delivering safe sedation to children.

PMID- 29179370
TI  - Use of Anesthesia Providers in the Administration of Office-based Deep
      Sedation/General Anesthesia to the Pediatric Dental Patient.

PMID- 29179371
TI  - Pediatric Restorative Dentistry.

PMID- 29179372
TI  - Pulp Therapy for Primary and Immature Permanent Teeth.

PMID- 29179373
TI  - Management of the Developing Dentition and Occlusion in Pediatric Dentistry.

PMID- 29179374
TI  - Dental Management of Heritable Dental Developmental Anomalies.

PMID- 29179375
TI  - Acquired Temporomandibular Disorders in Infants, Children, and Adolescents.

PMID- 29179376
TI  - Management Considerations for Pediatric Oral Surgery and Oral Pathology.

PMID- 29179377
TI  - Use of Antibiotic Therapy for Pediatric Dental Patients.

PMID- 29179378
TI  - Antibiotic Prophylaxis for Dental Patients at Risk for Infection.

PMID- 29179379
TI  - Dental Management of Pediatric Patients Receiving Chemotherapy, Hematopoietic
      Cell Transplantation, and/or Radiation Therapy.

PMID- 29179380
TI  - Record-keeping.

PMID- 29179381
TI  - Informed Consent.

PMID- 29179382
TI  - Guidelines for the Management of Traumatic Dental Injuries: 1. Fractures and
      Luxations of Permanent Teeth.
AB  - Traumatic dental injuries (TDIs) of permanent teeth occur frequently in children
      and young adults. Crown fractures and luxations are the most commonly occurring
      of all dental injuries. Proper diagnosis, treatment planning and followup are
      important for improving a favorable outcome. Guidelines should assist dentists
      and patients in decision making and for providing the best care effectively and
      efficiently. The International Association of Dental Traumatology (IADT) has
      developed a consensus statement after a review of the dental literature and group
      discussions. Experienced researchers and clinicians from various specialties were
      included in the group. In cases where the data did not appear conclusive,
      recommendations were based on the consensus opinion of the IADT board members.
      The guidelines represent the best current evidence based on literature search and
      professional opinion. The primary goal of these guidelines is to delineate an
      approach for the immediate or urgent care of TDIs. In this first article, the
      IADT Guidelines for management of fractures and luxations of permanent teeth will
      be presented.

PMID- 29179383
TI  - Guidelines for the Management of Traumatic Dental Injuries: 2. Avulsion of
      Permanent Teeth.
AB  - Avulsion of permanent teeth is one of the most serious dental injuries, and a
      prompt and correct emergency management is very important for the prognosis. The
      International Association of Dental Traumatology (IADT) has developed a consensus
      statement after a review of the dental literature and group discussions.
      Experienced researchers and clinicians from various specialties were included in
      the task group. The guidelines represent the current best evidence and practice
      based on literature research and professionals' opinion. In cases where the data
      did not appear conclusive, recommendations were based on the consensus opinion or
      majority decision of the task group. Finally, the IADT board members were giving
      their opinion and approval. The primary goal of these guidelines is to delineate
      an approach for the immediate orurgent care of avulsed permanent teeth.

PMID- 29179385
TI  - Policy on the Management of Patients with Cleft Lip/Palate and Other Craniofacial
      Anomalies.

PMID- 29179384
TI  - Guidelines for the Management of Traumatic Dental Injuries: 3. Injuries in the
      Primary Dentition.
AB  - Traumatic injuries to the primary dentition present special problems and the
      management is often different as compared with the permanent dentition. The
      International Association of Dental Traumatology (IADT) has developed a consensus
      statement after a review of the dental literature and group discussions.
      Experienced researchers and clinicians from various specialities were included in
      the task group. In cases where the data did not appear conclusive,
      recommendations were based on the consensus opinion or majority decision of the
      task group. Finally, the IADT board members were giving their opinion and
      approval. The primary goal of these guidelines is to delineate an approach for
      the immediate or urgent care for management of primary teeth injuries. The IADT
      cannot and does not guarantee favorable outcomes from strict adherence to the
      guidelines, but believe that their application can maximize the chances of a
      positive outcome.

PMID- 29179386
TI  - Periodontal Diseases of Children and Adolescents.

PMID- 29179387
TI  - Guideline for Periodontal Therapy.

PMID- 29179388
TI  - Treatment of Plaque-induced Gingivitis, Chronic Periodontitis, and Other Clinical
      Conditions.

PMID- 29179390
TI  - Growth Charts.

PMID- 29179391
TI  - Body Mass Index (BMI) Charts.

PMID- 29179389
TI  - Dental Growth and Development.

PMID- 29179392
TI  - Recommended USDA Food Patterns.

PMID- 29179393
TI  - Childhood and Adolescent Immunization Schedule.

PMID- 29179395
TI  - Pediatric Medical History.

PMID- 29179394
TI  - Speech and Language Milestones.

PMID- 29179397
TI  - Assessment of Acute Traumatic Injuries.

PMID- 29179396
TI  - Chairside Guide: Silver Diamine Fluoride in the Management of Dental Caries
      Lesions.

PMID- 29179398
TI  - Decision Trees for Management of an Avulsed Permanent Tooth.

PMID- 29179399
TI  - Preparing for Your Child's Sedation Visit.

PMID- 29179400
TI  - Sedation Record.

PMID- 29179401
TI  - Post-operative Instructions for Extractions/Oral Surgery.

PMID- 29179402
TI  - Record Transfer.

PMID- 29179403
TI  - Release for School Absences.

PMID- 29179404
TI  - Common Laboratory Values.

PMID- 29179406
TI  - Management of Medical Emergencies.

PMID- 29179405
TI  - Useful Medications for Oral Conditions.

PMID- 29179407
TI  - Basic Life Support/Cardiopulmonary Resuscitation.

PMID- 29179408
TI  - Delineation of Privileges.

PMID- 29179409
TI  - Considerations in Meta-Analyses to Understand the Value of Intravenous
      Thrombolysis in Current, Guideline-Based, Endovascular Practice of Stroke
      Treatment.

PMID- 29179410
TI  - Letter to the Editor Regarding "Efficacy of Early Surgery for Neurological
      Improvement in Spinal Cord Injury without Radiographic Evidence of Trauma in the
      Elderly".

PMID- 29179411
TI  - Letter to the Editor Regarding "Predictors of Shunt-Dependent Hydrocephalus After
      Aneurysmal Subarachnoid Hemorrhage? A Systematic Review and Meta-Analysis".

PMID- 29179412
TI  - In Reply to the Letter to the Editor Regarding "Predictors of Shunt-Dependent
      Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage? A Systematic Review and
      Meta-Analysis".

PMID- 29179413
TI  - Ambulatory Surgery and Social Inequalities in Industrialized Countries.

PMID- 29179414
TI  - In Reply to the Letter to the Editor "Ambulatory Surgery and Social Inequalities
      in Industrialized Countries".

PMID- 29179415
TI  - Fluorescein Sodium in Intracranial Meningioma Surgery.

PMID- 29179416
TI  - In Reply to the Letter to the Editor "Fluorescein Sodium in Intracranial
      Meningioma Surgery".

PMID- 29179417
TI  - Letter to the Editor Regarding "Relationship Between Koenig Depression Scale and
      Postoperative Outcomes, Ambulation, and Perception of Pain in Elderly Patients
      (>=65 Years) Undergoing Elective Spinal Surgery for Adult Scoliosis".

PMID- 29179418
TI  - In Reply to the Letter to the Editor Regarding "Relationship Between Koenig
      Depression Scale and Postoperative Outcomes, Ambulation, and Perception of Pain
      in Elderly Patients (>=65 Years) Undergoing Elective Spinal Surgery for Adult
      Scoliosis".

PMID- 29179419
TI  - Feasibility of Using a Superficial Temporal Artery Graft in Internal Maxillary
      Artery Bypass.

PMID- 29179420
TI  - In Reply to the Letter to the Editor "Feasibility of Using a Superficial Temporal
      Artery Graft in Internal Maxillary Artery Bypass".

PMID- 29179421
TI  - Enhancing Ethics in Peer Review Process.

PMID- 29179422
TI  - In Reply to the Letter to the Editor "Enhancing Ethics in Peer Review Process".

PMID- 29179423
TI  - Letter to the Editor Regarding "Presence of a Malignant Tumor as a Novel
      Predictive Factor for Repeated Recurrences of Chronic Subdural Hematoma".

PMID- 29179424
TI  - In Reply to the Letter to the Editor Regarding "Presence of a Malignant Tumor as
      a Novel Predictive Factor for Repeated Recurrences of Chronic Subdural Hematoma".

PMID- 29179425
TI  - Circumventricular Organ Origin of Hemangioblastoama; Hypothesis for Pathogenesis
      of Disease.

PMID- 29179426
TI  - In Reply to the Letter to the Editor "Circumventricular Organ Origin of
      Hemangioblastoama; Hypothesis for Pathogenesis of Disease".

PMID- 29179427
TI  - In Reply to the Letter to the Editor "Circumventricular Organ Origin of
      Hemangioblastoama; Hypothesis for Pathogenesis of Disease".

PMID- 29179428
TI  - Herb.

PMID- 29179429
TI  - Mutant calreticulin causes essential thrombocythemia.

PMID- 29179430
TI  - DOCK2: A novel FLT3/ITD leukemia drug target.

PMID- 29179431
TI  - Sleeping through the storm: Preventing myelosuppression with quizartinib.

PMID- 29179432
TI  - VAV2: a novel prognostic marker and a druggable target for adrenocortical
      carcinoma.

PMID- 29179433
TI  - Regulation of S-formylglutathione hydrolase by the anti-aging gene klotho.
AB  - Klotho is an aging-suppressor gene. The purpose of this study is to investigate
      the binding sites (receptors) and function of short-form Klotho (Skl). We showed
      that Skl physically bound to multiple proteins. We found physical and functional
      interactions between Skl and S-formylglutathione hydrolase (FGH), a key enzyme in
      the generation of the major cellular anti-oxidant GSH, using co
      immunoprecipitation-coupled mass spectrometry. We further confirmed the
      colocalization of Skl and FGH around the nucleus in kidney cells using
      immunofluorescent staining. Skl positively regulated FGH gene expression via Kid3
      transcription factor. Overexpression of Skl increased FGH mRNA and protein
      expression while silencing of Skl attenuated FGH mRNA and protein expression.
      Klotho gene mutation suppressed FGH expression in red blood cells and kidneys
      resulting in anemia and kidney damage in mice. Overexpression of Skl increased
      total GSH production and the GSH/GSSG ratio, an index of anti-oxidant capacity,
      leading to a decrease in intracellular H2O2 and superoxide levels. The
      antioxidant activity of Skl was eliminated by silencing of FGH, indicating that
      Skl increased GSH via FGH. Interestingly, Skl directly interacted with FGH and
      regulated its function. Site-directed mutagenesis of the N-glycan-modified
      residues in Skl abolished its antioxidant activity, suggesting that these N
      glycan moieties are important features that interact with FGH. Specific mutation
      of Asp to Ala at site 285 resulted in a loss of anti-oxidant activity of Skl,
      suggesting that N-glycosylation at site 285 is the key mechanism that determines
      Skl activity. Therefore, this study demonstrates, for the first time, that Skl
      regulates anti-oxidant GSH generation via interaction with FGH through N
      glycosylation.

PMID- 29179435
TI  - Genome-wide 5-hydroxymethylcytosine patterns in human spermatogenesis are
      associated with semen quality.
AB  - We performed immunofluorescent analysis of DNA hydroxymethylation and methylation
      in human testicular spermatogenic cells from azoospermic patients and ejaculated
      spermatozoa from sperm donors and patients from infertile couples. In contrast to
      methylation which was present throughout spermatogenesis, hydroxymethylation was
      either high or almost undetectable in both spermatogenic cells and ejaculated
      spermatozoa. On testicular cytogenetic preparations, 5-hydroxymethylcytosine was
      undetectable in mitotic and meiotic chromosomes, and was present exclusively in
      interphase spermatogonia Ad and in a minor spermatid population. The proportions
      of hydroxymethylated and non-hydroxymethylated diploid and haploid nuclei were
      similar among samples, suggesting that the observed alterations of 5
      hydroxymethylcytosine patterns in differentiating spermatogenic cells are
      programmed. In ejaculates, a few spermatozoa had high 5-hydroxymethylcytosine
      level, while in the other ones hydroxymethylation was almost undetectable. The
      percentage of highly hydroxymethylated (5-hydroxymethylcytosine-positive)
      spermatozoa varied strongly among individuals. In patients from infertile
      couples, it was higher than in sperm donors (P<0.0001) and varied in a wider
      range: 0.12-21.24% versus 0.02-0.46%. The percentage of highly hydroxymethylated
      spermatozoa correlated strongly negatively with the indicators of good semen
      quality - normal morphology (r=-0.567, P<0.0001) and normal head morphology (r=
      0.609, P<0.0001) - and strongly positively with the indicator of poor semen
      quality: sperm DNA fragmentation (r=0.46, P=0.001). Thus, the
      immunocytochemically detected increase of 5hmC in individual spermatozoa is
      associated with infertility in a couple and with deterioration of sperm
      parameters. We hypothesize that this increase is not programmed, but represents
      an induced abnormality and, therefore, it can be potentially used as a novel
      indicator of semen quality.

PMID- 29179436
TI  - Osteoblast-oriented differentiation of BMSCs by co-culturing with composite
      scaffolds constructed using silicon-substituted calcium phosphate, autogenous
      fine particulate bone powder and alginate in vitro.
AB  - Autogenous bone graft is the best for spinal fusion in clinics, however, lacking
      sources, bleeding and infection are limited its practice. Seeking alternative
      materials are urgent for orthopaedic surgeon. Here, we evaluated osteoblast
      oriented differentiation of rabbit BMSCs by co-culturing with composite scaffolds
      constructed using silicon-substituted-CaP-fine particulate bone powder-alginate.
      Using CCk8-kit, biocompatibility was evaluated by testing BMSCs proliferation;
      morphology and survival of osteoblasts within scaffolds were observed using EM
      and HE staining; growth factors and related genes were detected using RT-PCR. HE
      staining showed spindle-shaped BMSCs after the 3rd passage; EM data showed that
      uneven surface and longitudinal section were observed with scattered distribution
      of 5-100 mm interspaces, which leave enough space for BMSCs adhesion and growth.
      Interestingly, at 14-day culture with HE staining, osteocytes within the
      scaffolds grew well with regular shape and integrate structure. RT-PCR results
      showed that expression levels of BMP2, TGF-b and COL-I, ALP, OPN were increased
      significantly and time-dependently. Collectively, all mentioned effects were more
      obvious in co-culture BMSCs with scaffolds than those with other components.
      Immunohistochemistry showed that positive OPN expression was detected at 7-day co
      culturing BMSCs with scaffold, rather than other situations. These results
      suggest that composite scaffolds constructed with Si-CaP-fine particulate bone
      powder-alginate have a certain degree of biocompatibility and bioactivity to
      promote osteoblast-oriented BMSCs differentiation.

PMID- 29179434
TI  - Growth of malignant extracranial tumors alters microRNAome in the prefrontal
      cortex of TumorGraft mice.
AB  - A wide array of central nervous system complications, neurological deficits, and
      cognitive impairments occur and persist as a result of systemic cancer and cancer
      treatments. This condition is known as chemo brain and it affects over half of
      cancer survivors. Recent studies reported that cognitive impairments manifest
      before chemotherapy and are much broader than chemo brain alone, thereby adding
      in tumor brain as a component. The molecular mechanisms of chemo brain are under
      investigated, and the mechanisms of tumor brain have not been analyzed at all.
      The frequency and timing, as well as the long-term persistence, of chemo brain
      and tumor brain suggest they may be epigenetic in nature. MicroRNAs, small,
      single-stranded non-coding RNAs, constitute an important part of the cellular
      epigenome and are potent regulators of gene expression. miRNAs are crucial for
      brain development and function, and are affected by a variety of different
      stresses, diseases and conditions. However, nothing is known about the effects of
      extracranial tumor growth or chemotherapy agents on the brain microRNAome. We
      used the well-established TumorGraft TM mouse models of triple negative (TNBC)
      and progesterone receptor positive (PR+BC) breast cancer, and profiled global
      microRNAome changes in tumor-bearing mice upon chemotherapy, as compared to
      untreated tumor-bearing mice and intact mice. Our analysis focused on the
      prefrontal cortex (PFC), based on its roles in memory, learning, and executive
      functions, and on published data showing the PFC is a target in chemo brain. This
      is the first study showing that tumor presence alone significantly impacted the
      small RNAome of PFC tissues. Both tumor growth and chemotherapy treatment
      affected the small RNAome and altered levels of miRNAs, piRNAs, tRNAs, tRNA
      fragments and other molecules involved in post-transcriptional regulation of gene
      expression. Amongst those, miRNA changes were the most pronounced, involving
      several miRNA families, such as the miR-200 family and miR-183/96/182 cluster;
      both were deregulated in tumor-bearing and chemotherapy-treated animals. We saw
      that miRNA deregulation was associated with altered levels of brain-derived
      neurotrophic factor (BDNF), which plays an important role in cognition and memory
      and is one of the known miRNA targets. BDNF downregulation has been associated
      with an array of neurological conditions and could be one of the mechanisms
      underlying tumor brain and chemo brain. In the future our study could serve as a
      roadmap for further analysis of cancer and chemotherapy's neural side effects,
      and differentially expressed miRNAs should be explored as potential tumor brain
      and chemo brain biomarkers.

PMID- 29179439
TI  - Next generation sequencing identified novel heterozygous nonsense mutation in
      CNGB1 gene associated with retinitis pigmentosa in a Chinese patient.
AB  - Retinitis pigmentosa (RP) is a severe hereditary eye disease characterized by
      progressive degeneration of photoreceptors and subsequent loss of vision.
      Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of
      retinal diseases. Germline mutations of CNGB1 is associated with retinitis
      pigmentosa. We have identified and investigated a 34-year-old Chinese man with
      markedly have night vision blindness and loss of midperipheral visual field. The
      proband also lose his far peripheral visual field and also central vision.
      Proband's retinal pigment deposits visible on fundus examination and primary loss
      of rod photoreceptor cells followed by secondary loss of cone photoreceptors.
      Target exome capture based next generation sequencing and Sanger sequencing
      identified novel nonsense mutation, c.1917G>A and a reported mutation, c.2361C>A,
      in the CNGB1 gene. Both the nonsense mutations are predicted to lead to the
      formation of a premature stop codon which finally results into formation of
      truncated CNGB1 protein product which finally predicted to be disease causing.
      According to the variant classification guidelines of ACMG, these two variants
      are categorized as "likely pathogenic" variants. Our findings expand the
      mutational spectra of CNGB1 and are valuable in the mutation-based pre- and post
      natal screening and genetic diagnosis for retinitis pigmentosa.

PMID- 29179437
TI  - High glucose promotes vascular smooth muscle cell proliferation by upregulating
      proto-oncogene serine/threonine-protein kinase Pim-1 expression.
AB  - Serine/threonine kinase proviral integration site for Moloney murine leukemia
      virus 1 (Pim-1) plays an essential role in arterial wall cell proliferation and
      associated vascular diseases, including pulmonary arterial hypertension and
      aortic wall neointima formation. Here we tested a role of Pim-1 in high-glucose
      (HG)-mediated vascular smooth muscle cell (VSMC) proliferation. Pim-1 and
      proliferating cell nuclear antigen (PCNA) expression levels in arterial samples
      from streptozotocin-induced hyperglycemia rats were increased, compared with
      their weak expression in normoglycemic groups. In cultured rat VSMCs, HG led to
      transient Pim-1 expression decline, followed by sustained expression increase at
      both transcriptional and translational levels. Immunoblot analysis demonstrated
      that HG increased the expression of the 33-kDa isoform of Pim-1, but at much less
      extent to its 44-kDa plasma membrane isoform. D-glucose at a concentration of 25
      mmol/L showed highest activity in stimulating Pim-1 expression. Both Pim-1
      inhibitor quercetagetin and STAT3 inhibitor stattic significantly attenuated HG
      induced VSMC proliferation and arrested cell cycle progression at the G1 phase.
      Quercetagetin showed no effect on Pim-1 expression but decreased the
      phosphorylated-Bad (T112)/Bad ratio in HG-treated VSMCs. However, stattic
      decreased phosphorylated-STAT3 (Y705) levels and caused transcriptional and
      translational down-regulation of Pim-1 in HG-treated VSMCs. Our findings suggest
      HG-mediated Pim-1 expression contributes to VSMC proliferation, which may be
      partly due to the activation of STAT3/Pim-1 signaling.

PMID- 29179438
TI  - Valproate hampers podocyte acquisition of immune phenotypes via intercepting the
      GSK3beta facilitated NFkB activation.
AB  - Glomerular podocytes are able to transdifferentiate under disease conditions,
      acquire de novo immune phenotypes and behave as immunocompetent cells, like
      phagocytes or antigen-presenting cells. Upon stimulation with lipopolysaccharide
      (LPS), a prototypical pathogen-associated molecular pattern, podocytes
      demonstrated de novo expression of a variety of NFkB-dependent immune molecules
      that are pivotal for immune response, including major histocompatibility complex
      (MHC) class II, costimulatory molecule CD80, lysosomal protease cathepsin L as
      well as CC chemokine ligand 2 and 5, ultimately resulting in podocyte
      dysfunction, characterized by cellular shrinkage, a spindle-like or asterlike
      cell shape and impairment of actin cytoskeleton integrity. The LPS-elicited
      podocyte phenotypic changes were concurrent with nuclear factor (NF) kB
      phosphorylation, which was associated with glycogen synthase kinase (GSK) 3beta
      overactivity, marked by a diminished inhibitory phosphorylation of GSK3beta. In
      contrast, valproate, an anticonvulsant and mood stabilizer, offset GSK3beta
      overactivity in LPS-injured podocytes and mitigated NFkB activation and podocyte
      acquisition of immune phenotypes as well as the ensuing cytopathic changes,
      podocyte cytoskeleton disorganization and dysfunction. The protective effect of
      valproate was strikingly blunted in podocytes expressing the constitutively
      active GSK3beta, suggesting an essential role of inhibitory phosphorylation of
      GSK3beta. In vivo in LPS-injured mice, valproate therapy abolished GSK3beta
      overactivity in glomeruli and attenuated podocyte injury and albuminuria,
      concomitant with a lessened NFkB activation and diminished induction of diverse
      podocytopathic immune molecules in podocytes and glomeruli. Taken together,
      valproate directly protects against podocyte injury and hampers podocyte
      acquisition of de novo immune phenotypes via intercepting the GSK3beta
      facilitated NFkB activation.

PMID- 29179440
TI  - Toxoplasma gondii excretory/secretory antigens (TgESAs) suppress pro-inflammatory
      cytokine secretion by inhibiting TLR-induced NF-kappaB activation in LPS
      stimulated murine macrophages.
AB  - Excretory/secretory antigens (ESAs) produced by Toxoplasma gondii enable this
      parasite to invade and survive within the host cells through immunomodulation. In
      this study, the modulating effects of T. gondii excretory/secretory antigens
      (TgESAs) on the Ana-1 murine macrophage cell line were evaluated. Ana-1 cells
      were incubated with several concentrations of TgESAs, and the resulting effects
      on cellular viability, phagocytotic ability, and apoptosis induction were
      determined. Pro-inflammatory and anti-inflammatory cytokine secretion, nitric
      oxide production, toll-like receptor expression, and nuclear translocation of NF
      kappaB were all measured after incubation with TgESAs. After TgESAs treatment,
      the proliferation and phagocytosis ability of Ana-1 cells decreased, and
      apoptosis was induced in a dose dependent manner. Analysis of Ana-1 cell culture
      supernatants showed that TgESAs not only upregulated secretion of anti
      inflammatory cytokines (interleukin-10 and transforming growth factor-beta1),
      they also inhibited secretion of pro-inflammatory cytokines (tumor necrosis
      factor-alpha and interleukin-1beta). Additionally, TgESAs inhibited nitric oxide
      production, toll-like receptor (TLR) 2 and 4 activation, and the nuclear
      translocation of NF-kappaB in lipopolysaccharide-stimulated Ana-1 macrophages.
      These results suggest TgESAs inhibit the functional activity of Ana-1 murine
      macrophages by inhibiting TLR-induced NF-kappaB activation, which suppresses pro
      inflammatory cytokine secretion.

PMID- 29179441
TI  - High-affinity human PD-L1 variants attenuate the suppression of T cell
      activation.
AB  - The activated T cells can be suppressed by programed death-1 (PD-1) axis through
      low affinity interaction between PD-1 and PD-ligand 1 (PD-L1) in solution or on
      antigen presenting cells. In clinic, the concentration of soluble PD-L1 in
      peripheral blood negatively correlates with cancer prognosis. However, there is
      little information about the relation between the affinity of PD-1/PD-L1
      interaction and the suppressive capacity of PD-1 axis. In this study, we analyzed
      inhibitory roles of high affinity soluble human PD-L1 (hPD-L1) variants, which
      were generated with directed molecular evolution. Resultant two clones L3C7-hPD
      L1 and L3B3-hPD-L1 showed over 20 folds greater affinity than that of native hPD
      L1. We found that L3B3-hPD-L1 and L3C7-hPD-L1 could compete with an anti-PD-1
      antibody (EH12.1) for binding to hPD-1. More importantly, although native soluble
      hPD-L1 can induce suppressive effects on activated T cells, we found L3B3-hPD-L1
      and L3C7-hPD-L1 attenuated the strength of PD-1 axis for suppressing the
      proliferation and interferon gamma (IFN-gamma) secretion of PBMC. In conclusion,
      our data provide direct evidence in which immune checkpoint receptor-ligand
      interactive strength can alter the the suppressive function, in particular, the
      suppressive capacity of PD-1 axis could be decreased with enhanced affinity of
      soluble PD-L1 and PD-1 interaction. Our study might provide a new direction for
      manipulating immune checkpoints.

PMID- 29179442
TI  - A Bayesian pick-the-winner design in a randomized phase II clinical trial.
AB  - Purpose: Many phase II clinical trials evaluate unique experimental
      drugs/combinations through multi-arm design to expedite the screening process
      (early termination of ineffective drugs) and to identify the most effective drug
      (pick the winner) to warrant a phase III trial. Various statistical approaches
      have been developed for the pick-the-winner design but have been criticized for
      lack of objective comparison among the drug agents. Methods: We developed a
      Bayesian pick-the-winner design by integrating a Bayesian posterior probability
      with Simon two-stage design in a randomized two-arm clinical trial. The Bayesian
      posterior probability, as the rule to pick the winner, is defined as probability
      of the response rate in one arm higher than in the other arm. The posterior
      probability aims to determine the winner when both arms pass the second stage of
      the Simon two-stage design. Results: When both arms are competitive (i.e., both
      passing the second stage), the Bayesian posterior probability performs better to
      correctly identify the winner compared with the Fisher exact test in the
      simulation study. In comparison to a standard two-arm randomized design, the
      Bayesian pick-the-winner design has a higher power to determine a clear winner.
      In application to two studies, the approach is able to perform statistical
      comparison of two treatment arms and provides a winner probability (Bayesian
      posterior probability) to statistically justify the winning arm. Conclusion: We
      developed an integrated design that utilizes Bayesian posterior probability,
      Simon two-stage design, and randomization into a unique setting. It gives
      objective comparisons between the arms to determine the winner.

PMID- 29179443
TI  - SH003 suppresses breast cancer growth by accumulating p62 in autolysosomes.
AB  - Drug markets revisits herbal medicines, as historical usages address their
      therapeutic efficacies with less adverse effects. Moreover, herbal medicines save
      both cost and time in development. SH003, a modified version of traditional
      herbal medicine extracted from Astragalus membranaceus (Am), Angelica gigas (Ag),
      and Trichosanthes Kirilowii Maximowicz (Tk) with 1:1:1 ratio (w/w) has been
      revealed to inhibit tumor growth and metastasis on highly metastatic breast
      cancer cells, both in vivo and in vitro with no toxicity. Meanwhile, autophagy is
      imperative for maintenance cellular homeostasis, thereby playing critical roles
      in cancer progression. Inhibition of autophagy by pharmacological agents induces
      apoptotic cell death in cancer cells, resulting in cancer treatment. In this
      study, we demonstrate that SH003-induced autophagy via inhibiting STAT3 and mTOR
      results in an induction of lysosomal p62/SQSTM1 accumulation-mediated reactive
      oxygen species (ROS) generation and attenuates tumor growth. SH003 induced
      autophagosome and autolysosome formation by inhibiting activation of STAT3- and
      mTOR-mediated signaling pathways. However, SH003 blocked autophagy-mediated
      p62/SQSTM1 degradation through reducing of lysosomal proteases, Cathepsins,
      resulting in accumulation of p62/SQSTM1 in the lysosome. The accumulation of
      p62/SQSTM1 caused the increase of ROS, which resulted in the induction of
      apoptotic cell death. Therefore, we conclude that SH003 suppresses breast cancer
      growth by inducing autophagy. In addition, SH003-induced p62/SQSTM1 could
      function as an important mediator for ROS generation-dependent cell death
      suggesting that SH003 may be useful for treating breast cancer.

PMID- 29179444
TI  - Mechanism study of isoflavones as an anti-retinoblastoma progression agent.
AB  - Isoflavones, bioactive soy compounds, are known to exhibit anticancer activities.
      The present study investigated the anticancer activities of isoflavones on human
      retinoblastoma Y79 cells in vitro and in vivo. An MTT cell viability assay showed
      that the half maximal inhibitory concentration value of isoflavones against human
      retinoblastoma Y79 cells is 1.23 +/- 0.42 MUmol/l. Flow cytometry analysis
      indicated that isoflavones blocked G1/S progression. Western blot analysis
      demonstrated that the mammalian target of rapamycin (mTOR) pathway in Y79 cells
      was inhibited by isoflavones, with a concomitant decrease in cyclin E1, which
      accounted for the isoflavone-mediated G1 phase arrest. Isoflavones also inhibited
      human retinoblastoma growth in vivo; western blot analysis showed inhibition of
      mTOR and downregulation of cyclin E1 in an isoflavone-treated xenograft mouse
      model. Together, these results illustrate that isoflavones inhibit retinoblastoma
      tumour growth in vitro and vivo and that inactivation of the mTOR pathway and
      downregulation of cyclin E1 is involved in this action. The results of this study
      suggest that isoflavones could be tested as promising anti-retinoblastoma agent.

PMID- 29179446
TI  - Targeted interference of SIN3A-TGIF1 function by SID decoy treatment inhibits Wnt
      signaling and invasion in triple negative breast cancer cells.
AB  - Cancer cell invasion is an obligatory step for metastatic dissemination that
      contributes to rapid relapse and a poorer survival in triple negative breast
      cancer (TNBC) patients. Development of novel therapeutic strategies to block
      tumor invasion is an unmet need in the treatment of cancer. We reported that the
      selective inhibition of the PAH2 domain of SIN3A protein function markedly
      suppressed metastatic dissemination to the lungs in TNBC xenograft bearing mice.
      Here, we show that TNBC cell lines treated with Sin3 interaction domain (SID)
      decoy peptides that bind to PAH2 display a strong in vitro inhibition of
      transwell invasion. This is accompanied by actin cytoskeleton reorganization with
      increased cortical actin deposition and downregulation of known Wnt target genes
      that are associated with epithelial to mesenchymal transition (EMT) and cancer
      cell invasion. Wnt pathway inhibition by SID decoy peptide was confirmed by
      decreased Wnt reporter activity and altered cytoplasmic localization of nuclear
      beta-catenin. TGIF1, a transcription factor that modulates Wnt signaling and
      known to interact with the PAH2 domain of SIN3A, can be dissociated from the
      SIN3A complex by SID decoys. TGIF1 knockdown inhibits WNT target genes and in
      vitro cell invasion suggesting that TGIF1 might be a key target of the SID decoys
      to block tumor invasion. Taken together, targeting SIN3 function using SID decoys
      is a novel strategy to reverse invasion and the EMT program in TNBC translating
      into the inhibition of metastasis dissemination and eradication of residual
      disease.

PMID- 29179445
TI  - ADAMTS16 mutations sensitize ovarian cancer cells to platinum-based chemotherapy.
AB  - Ovarian cancer is one of the most lethal malignant tumors in women. The prognosis
      of ovarian cancer patients depends, in part, on their response to platinum-based
      chemotherapy. Our recent analysis of genomics and clinical data from the Cancer
      Genome Atlas demonstrated that somatic mutations of ADAMTS 1, 6, 8, 9, 15, 16, 18
      and L1 genes were associated with higher sensitivity to platinum and longer
      progression-free survival, overall survival, and platinum-free survival duration
      in 512 patients with high-grade serous ovarian carcinoma. Among the ADAMTS
      mutations, ADAMTS16 is the most commonly affected gene in ovarian cancer.
      However, the functional role of these mutations in ovarian cancer cells is
      largely unknown. We performed in vitro studies to compare the functional effects
      of the six identified ADAMTS missense mutations on the platinum sensitivity of
      ovarian cancer cells. We also used a well-characterized in vivo mouse model to
      evaluate the response of ovarian cancer cells with ADAMTS16 mutations to platinum
      based therapy. Our results showed that exogenously expressed ADAMTS16 missense
      mutations inhibited cell growth or sensitized tumor cells to cisplatin and
      inhibited tumor growth in vivo. Orthotopic xenograft experiments showed that mice
      injected with ovarian cancer cells that exogenously expressed ADAMTS16 mutations
      had a better response to cisplatin treatment. Thus, these functional studies
      provide evidence that mutations of ADAMTS16 actively contribute to therapeutic
      response in ovarian cancer.

PMID- 29179447
TI  - The tumor suppressor RASSF1A induces the YAP1 target gene ANKRD1 that is
      epigenetically inactivated in human cancers and inhibits tumor growth.
AB  - The Hippo pathway regulates organ size, growth and comprises several tumor
      related factors, including the oncoprotein YAP1 and the tumor suppressor RASSF1A.
      RASSF1A is frequently epigenetically inactivated in cancer. In our study, we
      analyzed the effect of RASSF1A on the function of YAP1. Expression of YAP1
      resulted in the downregulation of several tumor suppressor genes and induction of
      S-phase. Co-expression with RASSF1A normalized the expression levels of these
      tumor suppressors and induced a G0-G1 arrest and apoptosis. This effect was
      associated with the reduction of MDM2 and the increase of p53. These data suggest
      that the tumor suppressor RASSF1A inhibits the oncogenic potential of YAP1.
      Additionally, we could show that ANKRD1 is a YAP1 target gene that is induced by
      RASSF1A. Further analysis revealed that ANKRD1 is epigenetically inactivated in
      human cancer. ANKRD1 expression induced the expression of TP53 as well as BAX and
      CDKN1A and reduced colony formation of cancer cells. We found that ANKRD1
      interacts with p53 and is involved in the destabilization of MDM2. Additionally,
      our data indicate that the tumor-suppressive effect of ANKRD1 depends on the
      presence of p53. These results suggest that ANKRD1 is a tumor-suppressive
      downstream target of the Hippo pathway that is epigenetically silenced in human
      cancer.

PMID- 29179448
TI  - Overexpression of SYF2 promotes cell proliferation and correlates with poor
      prognosis in human breast cancer.
AB  - SYF2, a known cell cycle regulator, is reported to be involved in cell cycle
      arrest by interacting with cyclin-D-type binding protein 1. In the present study,
      we investigated the role of SYF2 in human breast cancer (BC) progression. SYF2
      was highly upregulated in BC tissues and cell lines, as per Western blot and
      immunohistochemistry analysis. The SYF2 expression level had a significant
      correlation with the tumor grade and Ki-67 expression. In vitro starvation
      refeeding experiment and SYF2-siRNA transfection assay demonstrated that SYF2
      could promote proliferation of BC cells, while SYF2 knockdown resulted in cells
      cycle arrest at G1/S phase, reducing the cell growth rate of BC cells. These
      results indicated that SYF2 promotes human BC progression by accelerating the BC
      cells' proliferation. SYF2 could be a novel therapeutic target in human BC
      therapies.

PMID- 29179449
TI  - The role of adrenomedullin in the pathogenesis of gastric cancer.
AB  - Adrenomedullin has been shown to be overexpressed in many tumors, including
      gastric cancer tumors; however, its mechanism of action remains unclear. In this
      study, we examined the role of adrenomedullin in the pathogenesis of gastric
      cancer. Using clinical specimens and immunohistochemistry, we found that the
      expression levels of adrenomedullin and its receptors are inordinately elevated
      as compared to the adjacent non-tumor gastric tissues. We used siRNA gene
      silencing, in BGC-823 gastric cancer cell lines, to target adrenomedullin genes,
      and found that increased adrenomedullin expression results in the proliferation
      of tumor cells, tumor invasion, and metastasis. Furthermore, we found that under
      hypoxic conditions, gastric cancer BGC-823 cells exhibit higher expression levels
      of adrenomedullin and various other related proteins. Our results indicate the
      involvement of adrenomedullin in microvessel proliferation and partially in the
      release of hypoxia in solid tumors. Knockdown of adrenomedullin expression, at
      the protein level, reduced the levels of phosphoprotein kinase B and B-cell
      lymphoma 2 but increased the levels of cleaved-caspase3 and Bcl 2 associated x
      protein (Bax). Therefore, we hypothesized siRNA targeting of adrenomedullin genes
      inhibits various serine/threonine kinases via a signaling pathway that induces
      cell apoptosis. SiRNA targeting of adrenomedullin genes and green fluorescent
      control vectors were used to transfect BGC-823 cells, and western blot analyses
      were used to detect changes in the rates of autophagy in related proteins using
      confocal laser scanning microscopy. No significant changes were detected.
      Therefore, the knockdown of adrenomedullin and its receptors may represent a
      novel treatment strategy for gastric cancer.

PMID- 29179451
TI  - Anti-cancer effects of dopamine in human glioma: involvement of mitochondrial
      apoptotic and anti-inflammatory pathways.
AB  - Despite the emergence of innovative cancer treatment strategies, the global
      burden imposed by malignant glioma is expected to increase; thus, new approaches
      for treating the disease are urgently required. Dopamine, a monoamine
      catecholamine neurotransmitter, is currently regarded as an important endogenous
      regulator of tumor growth. Dopamine may play an important role in glioma
      treatment; however, the mechanism underlying the anti-tumor activity of dopamine
      remains poorly understood. Here, we explored the potential roles of dopamine in
      glioma and highlight the importance of endogenous regulators of tumor growth. We
      report that dopamine inhibited glioma cell proliferation. We investigated the
      biological functions of dopamine via migration, colony formation and apoptosis
      assays in glioma cells. We also evaluated cytochrome c release from the
      mitochondria and p50 and p65 subcellular localization by fluorescence microscopy.
      We performed western blotting and real-time quantitative polymerase chain
      reaction to detect apoptosis and inflammatory marker protein and gene expression
      levels, respectively. NF-kappaB p50/p65 nuclear localization was analyzed after
      U87MG and U251 cells were treated with dopamine. The in vivo anti-tumor efficacy
      of dopamine was also analyzed in xenograft mice. Taken together, our results
      indicated that dopamine induced apoptosis by activating the cytochrome c and
      caspase-dependent apoptotic pathway. Moreover, dopamine markedly down-regulated
      inflammation-related protein expression levels and p50/p65 NF-kappaB nuclear
      localization in tumor cells, thereby inhibiting increases in tumor weight and
      size in xenograft mice. Thus, therapies targeting the mitochondrial apoptotic and
      anti-inflammatory signaling pathways regulated by dopamine may represent
      promising treatments for human glioma.

PMID- 29179452
TI  - Novel galeterone analogs act independently of AR and AR-V7 for the activation of
      the unfolded protein response and induction of apoptosis in the CWR22Rv1 prostate
      cancer cell model.
AB  - The androgen receptor (AR) has long been the primary target for the treatment of
      prostate cancer (PC). Despite continuous efforts to block AR activity through
      ligand depletion, AR antagonism, AR depletion and combinations thereof, advanced
      PC tumors remain resilient. Herein, we evaluate two galeterone analogs, VNPT-178
      and VNLG-74A, in PC cell models of diverse androgen and AR dependence attempting
      to delineate their mechanisms of action and potential clinical utility. Employing
      basic biochemical techniques, we determined that both analogs have improved
      antiproliferative and anti-AR activities compared to FDA-approved abiraterone and
      enzalutamide. However, induction of apoptosis in these models is independent of
      the AR and its truncated variant, AR-V7, and instead likely results from
      sustained endoplasmic reticulum stress and deregulated calcium homeostasis. Using
      in silico molecular docking, we predict VNPT-178 and VNLG-74A bind the ATPase
      domain of BiP/Grp78 and Hsp70-1A with greater affinity than the AR. Disruption of
      70 kDa heat shock protein function may be the underlying mechanism of action for
      these galeterone analogs. Therefore, despite simultaneously antagonizing AR
      activity, AR and/or AR-V7 expression alone may inadequately predict a patient's
      response to treatment with VNPT-178 or VNLG-74A. Future studies evaluating the
      context-specific limitations of these compounds may provide clarity for their
      clinical application.

PMID- 29179450
TI  - Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin
      II in breast cancer cells.
AB  - Angiotensin (Ang) II, the main effector peptide of the renin-angiotensin system,
      has been implicated in multiple aspects of cancer progression such as
      proliferation, migration, invasion, angiogenesis and metastasis. Ang-(1-7), is a
      biologically active heptapeptide, generated predominantly from AngII by the
      enzymatic activity of angiotensin converting enzyme 2. Previous studies have
      shown that Ang-(1-7) counterbalances AngII actions in different
      pathophysiological settings. In this study, we have analysed the impact of Ang-(1
      7) on AngII-induced pro-tumorigenic features on normal murine mammary epithelial
      cells NMuMG and breast cancer cells MDA-MB-231. AngII stimulated the activation
      of the survival factor AKT in NMuMG cells mainly through the AT1 receptor. This
      PI3K/AKT pathway activation also promoted epithelial-mesenchymal transition
      (EMT). Concomitant treatment of NMuMG cells with AngII and Ang-(1-7) completely
      abolished EMT features induced by AngII. Furthermore, Ang-(1-7) abrogated AngII
      induced migration and invasion of the MDA-MB-231 cells as well as pro-angiogenic
      events such as the stimulation of MMP-9 activity and VEGF expression. Together,
      these results demonstrate for the first time that Ang-(1-7) counteracts tumor
      aggressive signals stimulated by AngII in breast cancer cells emerging the
      peptide as a potential therapy to prevent breast cancer progression.

PMID- 29179453
TI  - MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver
      carcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is the fastest-rising cause of cancer-related
      death in the United States. Recent epidemiological studies have identified
      nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty
      liver disease (NAFLD), as a major risk factor for HCC. Elucidating the underlying
      mechanisms associated with the development of NASH-derived HCC is critical for
      identifying early biomarkers for the progression of the disease and for treatment
      and prevention. In the present study, using liver samples from C57BL/6J mice
      submitted to the Stelic Animal Model (STAM) of NASH-associated liver
      carcinogenesis, we investigated the role of microRNA (miRNA) alterations in the
      pathogenesis of NASH-derived HCC. We found substantial alterations in the
      expression of miRNAs, with the greatest number occurring in full-fledged HCC.
      Mechanistically, altered miRNA expression was associated with activation of major
      hepatocarcinogenesis-related pathways, including the TGF-beta, Wnt/beta-catenin,
      ERK1/2, mTOR, and EGF signaling. In addition, the over-expression of the miR-221
      3p and miR-222-3p and oncogenic miR-106b~25 cluster was accompanied by the
      reduced protein levels of their targets, including E2F transcription factor 1
      (E2F1), phosphatase and tensin homolog (PTEN), and cyclin-dependent kinase
      inhibitor 1 (CDKN1A). Importantly, miR-93-5p, miR-221-3p, and miR-222-3p were
      also significantly over-expressed in human HCC. These findings suggest that
      aberrant expression of miRNAs may have mechanistic significance in NASH
      associated liver carcinogenesis and may serve as an indicator for the development
      of NASH-derived HCC.

PMID- 29179454
TI  - Plasma microRNA alterations between EGFR-activating mutational NSCLC patients
      with and without primary resistance to TKI.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have
      obtained excellent therapeutic effects against non-small cell lung cancer (NSCLC)
      harboring activating EGFR mutations. However, some patients have exhibited
      primary resistance which becomes a major obstacle in effective treatment of
      NSCLC. The mechanisms of EGFR-TKIs resistance involved are still poorly
      understood. Many studies suggest that miRNAs play an important role in regulating
      drug sensitivity of EGFR-TKIs. The aim of the present study was to examine
      differentially expressed miRNAs in plasma between EGFR-TKIs sensitive and EGFR
      TKIs primary resistance patients. MiRNA microarray of plasma from patients' blood
      identified 16 differentially expressed miRNAs of which 15 (hsv2-miR-H19, hsa-miR
      744-5p, hsa-miR-3196, hsa-miR-3153, hsa-miR-4791, hsa-miR-4803, hsa-miR-4796-3p,
      hsa-miR-372-5p, hsa-miR-138-2-3p, hsa-miR-16-1-3p, hsa-miR-1469, hsa-miR-585-3p,
      ebv-miR-BART14-5p, hsa-miR-769-3p, hsa-miR-548aq-5p) were down regulated while
      only hsa-miR-503-3p was up regulated in primary resistant patients' plasma.
      Volcano plot and hierarchical clustering were performed to examine the accuracy
      of the miRNAs. Then validation with quantitative real-time PCR was performed and
      the result was in accordance with the array data. Functional analysis of these
      differentially expressed miRNAs with Ingenuity Pathway Analysis (IPA) revealed a
      common signaling network including MYC, CCND1, IGF1 and RELA. In conclusion, our
      finding may play important role in understanding the mechanisms underlying the
      problem and should be further evaluated as potential biomarkers in primary
      resistance of NSCLC.

PMID- 29179455
TI  - Lack of adiponectin and adiponectin receptor 1 contributes to benign prostatic
      hyperplasia.
AB  - PURPOSE: The incidence of benign prostatic hyperplasia increases among obese
      individuals, but few studies have fully explained the underlying mechanisms.
      Adiponectin has drawn much attention in recent years due to its protective role
      in obesity-related diseases. Here we aimed to investigate the possible molecular
      mechanisms and clinical significance of adiponectin in relation to benign
      prostatic hyperplasia. METHODS: We analyzed data from 98 Chinese men, including
      48 BPH cases and 50 controls in a case-control study. Then, we utilized a tissue
      microarray analysis to examine expression of AdipoR1 and p-p90RSK in normal and
      hyperplastic prostate tissues. These studies were followed by various in vitro
      approaches to examine the anti-proliferation effect and signaling pathways of
      adiponectin involved in benign prostatic hyperplasia. RESULTS: Lower serum
      adiponectin levels were independently associated with larger prostate volume and
      an increased risk of benign prostatic hyperplasia. Benign prostatic hyperplasia
      tissues had a decreased expression of AdipoR1 and increased expression of p
      p90RSK compared with normal prostate tissues. in vitro, adiponectin inhibited the
      proliferation of prostatic epithelial and stromal cells and arrested cells in the
      G0/G1 phase by decreasing phosphorylation of the MEK-ERK-p90RSK axis.
      CONCLUSIONS: Our results suggest a possible negative regulatory mechanism in
      which adiponectin signaling antagonizes ERK-mediated cell proliferation, and a
      deficiency in adiponectin could facilitate the proliferation of prostate cells
      and consequently contribute to benign prostatic hyperplasia.

PMID- 29179456
TI  - Combined Ki67 and ERCC1 for prognosis in non-keratinizing nasopharyngeal
      carcinoma underwent chemoradiotherapy.
AB  - This study aimed to assess the predictive value of combined Ki67 and ERCC1 in
      distant metastasis-free nasopharyngeal carcinoma. 334 such cases were
      retrospectively assessed. Immunohistochemistry was used to evaluate Ki67 and
      ERCC1 protein levels in tumor tissues. Associations of Ki67 and ERCC1 amounts
      with clinical characteristics and survival were analyzed. Medium follow-up was
      48.7 months; overall survival (OS), disease-free survival (DFS), distant
      metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) were
      91.3%, 76.0%, 82.0%, and 91.9%, respectively. High Ki67 expression was found in
      35.6% patients, and positively correlated with clinical- and N- staging (P =
      0.005, P < 0.001); 4-year OS, DFS, and DMFS were significantly lower in the high
      Ki67 group than patients with low-medium expression (P = 0.001, P = 0.012, P =
      0.007). High ERCC1 expression was found in 35.3% of patients, and positively
      correlated with clinical- and T- staging. Compared with low ERCC1 expression
      cases, 4-year OS, DFS, DMFS, and LRFS were decreased significantly in those with
      high levels. High Ki67 and ERCC1 levels were related to adverse prognoses of OS
      (HR=4.977, 95% CI 2.31-12.292, P<0.001), DFS (HR = 4.178, 95% CI 2.421-7.212, P <
      0.001), DMFS (HR = 3.722, 95% CI 2.028-7.015, P < 0.001), and LRFS (HR = 3.689,
      95% CI 1.423-9.566, P = 0.007). Compared with the low-medium Ki67 and low ERCC1
      groups, no significant difference in survival prognosis was obtained in the low
      medium Ki67 and high ERCC1 groups, and patients with high Ki67 and low ERCC1
      levels. Combined Ki67 and ERCC1 can better predict nasopharyngeal carcinoma
      prognosis than individual parameters.

PMID- 29179457
TI  - Traditional Chinese medicine Danggui Buxue Tang inhibits colorectal cancer growth
      through induction of autophagic cell death.
AB  - Purpose: The induction of autophagic cell death is an important process in the
      development of anticancer therapeutics. We aimed to evaluate the activity of the
      ancient Chinese decoction Danggui Buxue Tang (DBT) against colorectal cancer
      (CRC) and the associated autophagy-related mechanism. Materials and methods: CT26
      CRC cells were implanted into syngeneic BALB/c mice for the tumor growth assay.
      DBT extracts and DBT-PD (polysaccharide-depleted) fractions were orally
      administered. The toxicity profiles of the extracts were analyzed using
      measurements of body weight, hemogram, and biochemical parameters. The morphology
      of tissue sections was observed using light and transmission electron microscopy.
      Western blotting and small interference RNA assays were used to determine the
      mechanism. Results: DBT-PD and DBT, which contained an equal amount of DBT-PD,
      inhibited CT26 syngeneic tumor growth. In the tumor specimen, the expression of
      microtubule-associated proteins 1A/1B light chain 3B (LC3B) was upregulated by
      DBT-PD and DBT. The development of autophagosomes was observed via transmission
      electron microscopy in tumors treated with DBT-PD and DBT. In vitro experiments
      for mechanism clarification demonstrated that DBT-PD could induce autophagic
      death in CT26 cells accompanied by LC3B lipidation, downregulation of phospho
      p70s6k, and upregulation of Atg7. RNA interference of Atg7, but not Atg5,
      partially reversed the effect of DBT-PD on LC3B lipidation and expression of
      phospho-p70s6k and Atg7. The changes in ultrastructural morphology and LC3B
      expression induced by DBT-PD were also partially blocked by the knockdown of Atg7
      mRNA. Conclusion: DBT induced autophagic death of colorectal cancer cells through
      the upregulation of Atg7 and modulation of the mTOR/p70s6k signaling pathway.

PMID- 29179458
TI  - Plasma N-acetylputrescine, cadaverine and 1,3-diaminopropane: potential
      biomarkers of lung cancer used to evaluate the efficacy of anticancer drugs.
AB  - Polyamines have been widely investigated as potential biomarkers for various
      types of cancers, including lung cancer, which is one of the most common causes
      of death from cancer worldwide. This study was carried out to evaluate the value
      of polyamines that serve as early diagnostic and cancer progression markers as
      well as drug evaluation for lung cancer (squamous cell carcinoma of lung, SCCL).
      SCCL was induced in Wistar rats by intratracheal instillation of 3
      methylcholanthrene and treated with three different anti-cancer drugs, Aidi
      injections, fluorouracil, and a combination of them. After carcinogenesis for 28,
      70 and 98 days and therapy for 28 and 56 days, the polyamine levels in plasma of
      SCCL, healthy and treated rats were determined using a UHPLC-MS/MS assay base on
      the means of targeted metabolomics. Results showed that increased N
      acetylputrescine, cadaverine and 1,3-diaminopropane levels were associated with
      progression of SCCL. The levels of cadaverine and 1,3-diaminopropane returned to
      normal after administration of the three different kinds of anticancer drug. In
      addition, the suitability of using N-acetylputrescine, cadaverine and 1,3
      diaminopropane as biomarkers was confirmed by PLS-DA and ROC analysis. It can
      provide an innovative and effective way for the clinical diagnosis, prevention
      and treatment of lung cancer, and stimulate a theoretical basis for the design
      and development of new anticancer drugs. At the same time, this increased the
      clinical options for polyamines as cancer biomarkers.

PMID- 29179459
TI  - SLC3A2, antigen of mAb 3G9, promotes migration and invasion by upregulating of
      mucins in gastric cancer.
AB  - Solute carrier family 3 member 2 (SLC3A2) has been reported to be highly
      expressed in a variety of carcinomas. However, the function of SLC3A2 in gastric
      carcinoma (GC) has not been well explored. Monoclonal antibody (mAb) 3G9,
      generated from immunogen of various human GC cell lines, has been shown to bind
      to GC tissues specifically. In this study, we identified the target antigen of
      mAb 3G9 as SLC3A2, and detected the expression profile of SLC3A2 in a panel of
      gastric cancer cell lines and GC tumor tissues. We found that the increased
      expression of SLC3A2 was associated with serosal invasion in GC patients.
      Knockout of SLC3A2 suppressed the migration and invasion of BGC-823 cells in
      vitro and in vivo, whereas overexpression of SLC3A2 in NCI-N87 cells promoted the
      migration and invasion in vitro and in vivo. Mechanistic investigations suggested
      that MUC1, MUC16 and MUC5B were the downstream genes of SLC3A2 in GC cells. Taken
      together, our data suggested that SLC3A2 promoted the aggressive phenotype of GC
      by upregulating several mucin genes expression and may serve as a potential
      biomarker for diagnosis and target therapy.

PMID- 29179460
TI  - GSK-3beta phosphorylation-dependent degradation of ZNF281 by beta-TrCP2
      suppresses colorectal cancer progression.
AB  - Zinc finger protein 281 (ZNF281) has been recently shown to be critical for CRC
      progression. However, the immediate upstream regulators of ZNF281 remain unclear.
      Here we reported that the E3 ligase the beta-transducin repeat-containing protein
      2 (beta-TrCP2) governs the ubiquitination and degradation of ZNF281. In human CRC
      specimens, endogenous beta-TrCP2 were inversely correlated with ZNF281. Beta
      TrCP2 reversed the phenotype of CRC cell with overexpressed ZNF281. Moreover, we
      found that glycogen synthase kinase 3beta (GSK-3beta), not GSK-alpha, could bind
      to and phosphorylate ZNF281 at one consensus motif (TSGEHS; phosphorylation site
      is shown in italics), which promotes the interaction of ZNF281 with beta-TrCP2,
      not beta-TrCP1, and leads to the subsequent ubiquitination and degradation of
      phosphorylated ZNF281. A mutant of ZNF281 (ZNF281-S638A) is much more stable than
      wild-type ZNF281 because ZNF281-S638A mutant abolishes the phosphorylation by GSK
      3beta and can not be ubiquitinated and degraded by beta-TrCP2. Conversely, ZNF281
      transcriptionally repressed the expression of beta-TrCP2, indicating a negative
      feedback loop between ZNF281 and beta-TrCP2 in CRC cells. These findings suggest
      that the turnover of ZNF281 by beta-TrCP2 might provide a potentially novel
      treatment for patients with CRC.

PMID- 29179461
TI  - Differential expression profiles of long non-coding RNAs as potential biomarkers
      for the early diagnosis of acute myocardial infarction.
AB  - Acute myocardial infarction (AMI) is a major cause of morbidity and mortality
      worldwide. The early diagnosis of AMI is crucial for deciding the course of
      treatment and saving lives. Long non-coding RNAs (lncRNAs) are recently
      discovered ncRNA class and their dysregulated expression has been implicated in
      cardiovascular diseases. In this study, we analyzed lncRNA expression pattern by
      using two microarray datasets of AMI and healthy samples from the Gene Expression
      Omnibus (GEO) database and tried to identify novel AMI-related lncRNAs and
      investigate the predictive roles of lncRNAs in the early diagnosis of AMI. From
      the discovery cohort, 11 differentially expressed lncRNAs were identified as
      candidate biomarkers that were validated in the discovery cohort, internal cohort
      and an independent cohort, respectively. Hierarchical clustering analysis
      suggested that the expression pattern of these 11 candidate lncRNA biomarkers was
      closely associated with disease status of samples. Then a lncRNA risk classifier
      was developed by integrating expression value of 11 differentially expressed
      lncRNAs using support vector machine (SVM) algorithm. The results of leaving one
      out cross-validation (LOOCV) suggested that the lncRNA risk classifier has a good
      discrimination between AMI patients and healthy samples with the area under ROC
      curve (AUC) of 0.955, 0.92 and 0.701 in three cohorts, respectively. Functional
      enrichment analysis suggested that these 11 candidate lncRNA biomarkers might be
      involved in inflammation- and immune-related biological processes. Our study
      indicates the potential roles in the early diagnosis of AMI and will improve our
      understanding of the molecular mechanism of the occurrence and recurrence of AMI.

PMID- 29179462
TI  - Toll-like receptor 5 gene polymorphism is associated with breast cancer
      susceptibility.
AB  - Toll-like receptor 5 (TLR5) plays a fundamental role in immune responses. Recent
      findings suggest the TLR5 expression level affects cancer progression and
      development. In the present study, our examination of 256 breast carcinomas
      specimens revealed that TLR5 is overexpressed in breast carcinomas, and that TLR5
      overexpression correlated with lymph node metastasis and cancer grade (p<0.01).
      In a case-control study, we also analyzed associations between TLR5 single
      nucleotide polymorphisms (SNPs) and breast cancer risk. Compared were 516 Chinese
      Han women diagnosed mainly with infiltrative ductal carcinoma and 520 age-matched
      healthy controls. The nonsense SNP rs5744168 causes truncation of the TLR5
      transmembrane signaling domain and was associated with breast cancer risk
      (p<0.05). However, no statistical association was detected between SNP rs5744168
      and any of the clinical parameters tested. Our findings thus indicate that TLR5
      SNP rs5744168 is associated with sporadic breast cancer occurrence.

PMID- 29179463
TI  - Olaquindox disrupts tight junction integrity and cytoskeleton architecture in
      mouse Sertoli cells.
AB  - Sertoli cells, by creating an immune-privileged and nutrition supporting
      environment, maintain mammalian spermatogenesis and thereby holds the heart of
      male fertility. Olaquindox, an effective feed additive in livestock industry,
      could potentially expose human into the risk of biological hazards due to its
      genotoxicity and cytotoxicity, highlighting the significance of determining its
      bio-safety regarding human reproduction. Herein, we deciphered the detrimental
      effects of olaquindox on male fertility by mechanistically unraveling how
      olaquindox intervenes blood-testis barrier in mouse. Olaquindox (400 MUg/ml)
      exposure significantly compromised tight junction permeability function,
      decreased or dislocated the junction proteins (e.g., ZO-1, occludin and N
      cadherin) and attenuated mTORC2 signaling pathway in primary Sertoli cells.
      Furthermore, olaquindox disrupted F-actin architecture through interfering with
      the expression of actin branching protein complex (CDC42-N-WASP-Arp3) and actin
      bunding protein palladin. Olaquindox also triggered severely DNA damage and
      apoptosis while inhibiting autophagic flux in Sertoli cell presumably due to the
      exacerbated generation of reactive oxygen species (ROS). Pre-treatment with
      antioxidant N-acetylcysteine effectively ameliorated olaquindox-induced
      exhaustion of ZO-1 and N-Cadherin proteins, DNA damage and apoptosis. More
      significantly, olaquindox disrupted the epigenetic status in Sertoli cells with
      hypermethylation and concomitantly hypoacetylation of H3K9 and H3K27. Overall,
      our study determines olaquindox targets Sertoli cells to affect BTB function
      through tight junction proteins and F-actin orgnization, which might disrupt the
      process of spermatogenesis.

PMID- 29179464
TI  - Urokinase-type plasminogen activator receptor inhibits apoptosis in triple
      negative breast cancer through miR-17/20a suppression of death receptors 4 and 5.
AB  - Dissection and understanding of the molecular pathways driving triple-negative
      breast cancer (TNBC) are urgently needed to develop efficient tailored therapies.
      Aside from cell invasion and metastasis, the urokinase-type plasminogen activator
      receptor (uPAR) has been linked to apoptosis resistance in breast tumors. We
      explored the mechanism of uPAR-disrupted apoptosis in breast cancer. We found
      that depletion of uPAR by RNAi increases death receptor 4 (DR4) and death
      receptor 5 (DR5) expression and triggers TRAIL-induced apoptosis in TNBC cells.
      The microRNAs miR-17-5p and miR-20a inhibit cell apoptosis via suppression of
      DR4/DR5. We provide evidence that uPAR enhances miR-17-5p/20a expression through
      upregulation of c-myc. Blocking miR-17-5p/20a with antagomiRNA suppressed the
      growth of uPAR-overexpressing breast tumor xenografts in mice. These results
      indicate that uPAR suppresses cell apoptosis by inhibiting the c-myc-miR
      17/5p/20a-DR4/DR5 pathway. Therapy directed at uPAR-induced miR-17/20a is a
      potential option for breast cancer and TNBC.

PMID- 29179465
TI  - Shikonin reduces tamoxifen resistance through long non-coding RNA uc.57.
AB  - Tamoxifen resistance is a serious problem in the endocrine therapy of breast
      cancer. Long non-coding RNAs play important roles in tumor development. In this
      study, we revealed the involvement of lncRNA uc.57 and its downstream gene BCL11A
      in TAM resistance. Tamoxifen-resistant MCF-7R cells showed lower expression of
      uc.57 and higher expression of BCL11A mRNA and protein than the parental MCF-7
      cells. Moreover, levels of uc.57 mRNA were lower and BCL11A mRNA were higher in
      breast cancer tissues than in precancerous breast tissues. Shikonin treatment
      reduced tamoxifen resistance in MCF-7R cells both in vitro and in vivo, targeting
      uc.57/BCL11A. Fluorescence in situ hybridization and RNA immunoprecipitation
      analyses showed that uc.57 binds to BCL11A. Uc.57 overexpression downregulated
      BCL11A and reduced tamoxifen resistance in MCF-7R cells both in vitro and in
      vivo. BCL11A knockdown also reduced tamoxifen resistance by inhibiting PI3K/AKT
      and MAPK signaling pathways. It thus appears shikonin reduces tamoxifen
      resistance of MCF-7R breast cancer cells by inducing uc.57, which downregulates
      BCL11A to inhibit PI3K/AKT and MAPK signaling pathways.

PMID- 29179466
TI  - Anti-angiogenic drugs: direct anti-cancer agents with mitochondrial mechanisms of
      action.
AB  - Components of the mitochondrial electron transport chain have recently gained
      much interest as potential therapeutic targets. Since mitochondria are essential
      for the supply of energy that is required for both angiogenic and tumourigenic
      activity, targeting the mitochondria represents a promising potential therapeutic
      approach for treating cancer. Here we investigate the established anti
      angiogenesis drugs combretastatin A4, thalidomide, OGT 2115 and tranilast that we
      hypothesise are able to exert a direct anti-cancer effect in the absence of
      vasculature by targeting the mitochondria. Drug cytotoxicity was measured using
      the MTT assay. Mitochondrial function was measured in intact isolated
      mitochondria using polarography, fluorimetry and enzymatic assays to measure
      mitochondrial oxygen consumption, membrane potential and complex I-IV activities
      respectively. Combretastatin A4, OGT 2115 and tranilast were both shown to
      decrease mitochondrial oxygen consumption. OGT 2115 and tranilast decreased
      mitochondrial membrane potential and reduced complex I activity while
      combretastatin A4 and thalidomide did not. OGT 2115 inhibited mitochondrial
      complex II-III activity while combretastatin A4, thalidomide and tranilast did
      not. Combretastatin A4, thalidomide and OGT 2115 induced bi-phasic concentration
      dependent increases and decreases in mitochondrial complex IV activity while
      tranilast had no evident effect. These data demonstrate that combretastatin A4,
      thalidomide, OGT 2115 and tranilast are all mitochondrial modulators. OGT 2115
      and tranilast are both mitochondrial inhibitors capable of eliciting
      concentration-dependent reductions in cell viability by decreasing mitochondrial
      membrane potential and oxygen consumption.

PMID- 29179467
TI  - Knockdown of long non-coding RNA Taurine Up-Regulated 1 inhibited doxorubicin
      resistance of bladder urothelial carcinoma via Wnt/beta-catenin pathway.
AB  - In genitourinary system, bladder cancer (BC) is the most common and lethal
      malignant tumor, which most common type is bladder urothelial carcinoma (BUC).
      Long non-coding RNA (lncRNA) Taurine Up-Regulated 1 (TUG1) gene is high-expressed
      in several malignant tumors, including BC. In this study, over-expression of TUG1
      was found in BUC tissues and cell line resistant to doxorubicin (Dox). Knockdown
      of TUG1 inhibited the Dox resistance and promoted the cytotoxicity induced by Dox
      in T24/Dox cells. TUG1 knockdown also depressed the Wnt/beta-catenin pathway, and
      the activation the Wnt/beta-catenin pathway partly reversed the inhibitory
      effects of TUG1 knockdown on Dox resistance in T24/Dox cells. In conclusion, up
      regulation of lncRNA TUG1 was related with the poor response of BUC patients to
      Dox chemotherapy, knockdown of TUG1 inhibited the Dox resistance of BUC cells via
      Wnt/beta-catenin pathway. These findings might assist in the discovery of novel
      potential diagnostic and therapeutic target for BUC, thereby improve the effects
      of clinical treatment in patients.

PMID- 29179468
TI  - Pharmacometabolomics identifies dodecanamide and leukotriene B4 dimethylamide as
      a predictor of chemosensitivity for patients with acute myeloid leukemia treated
      with cytarabine and anthracycline.
AB  - Clinical responses to standard cytarabine plus anthracycline regimen in acute
      myeloid leukemia (AML) are heterogeneous and there is an unmet need for
      biological predictors of response to this regimen. Here, we applied a
      pharmacometabolomics approach to identify potential biomarkers associated with
      response to this regimen in AML patients. Based on clinical response the enrolled
      82 patients were subdivided into two groups: complete remission(CR) responders
      (n=42) and non-responders (n=40). Metabolic profiles of pre-treatment serum from
      patients were analyzed by ultra-high performance liquid chromatography coupled
      with mass spectrometry and the metabolic differences between the two groups were
      investigated by multivariate statistical analysis. A metabolite panel containing
      dodecanamide and leukotriene B4 dimethylamide (LTB4-DMA) had the power capacity
      to differentiate the two groups of patients, yielding an area under the receiver
      operating characteristic of 0.945 (85.2% sensitivity and 88.9% specificity) in
      the training set and 0.944(84.6% sensitivity and 80.0% specificity) in the test
      set. The patients with high levels of LTB4-DMA and low amounts of dodecanamide
      had good sensitivity to chemotherapeutic agents. The possible reasons were that
      dodecanamide was produced by leukemic cells as a lipolytic factor to fuel their
      growth with a potential role in drug resistance and LTB4-DMA was a potent
      leukotriene B4 antagonist that could be applicable in the treatment of AML. These
      preliminary results demonstrates the feasibility of relating chemotherapy
      responses with pre-treatment metabolic profiles of AML patients, and
      pharmacometabolomics may be a useful tool to select patients that are more likely
      to benefit from cytarabine plus anthracycline chemotherapy.

PMID- 29179469
TI  - Bioluminescence imaging of a tumor-selective, thymidine kinase-defective vaccinia
      virus Guang9 strain after intratumoral or intraperitoneal administration in mice.
AB  - Vaccinia virus has been used as an oncolytic virus because of its capacity to
      preferentially infect tumors rather than normal tissues. The vaccinia Tian Tan
      strain, used as a vaccine against smallpox for millions of people in China, is a
      promising candidate for cancer therapy. In this study, we constructed an
      attenuated Tian Tan strain of Guang9 with a disrupted thymidine kinase gene to
      enhance tumor selectivity and an inserted firefly luciferase to monitor the viral
      distribution by in vivo bioluminescence imaging. Living animal imaging confirmed
      the high specificity of vaccinia Guang9 for tumor targeting after intratumoral
      and intraperitoneal administration. In addition, the vaccinia Guang9 strain
      produced higher in vivo luciferase activity and endured longer in
      immunocompromised nude mice than in immunocompetent C57BL/6 mice, all of which
      had been tumor-challenged. The luciferase activity and viral titers in excised
      tissues confirmed these conclusions. These data provide evidence for the safety
      and efficacy of the clinical application of vaccinia virus, which would be a
      promising approach for cancer therapy.

PMID- 29179470
TI  - Constitutive activated STAT3 is an essential regulator and therapeutic target in
      esophageal squamous cell carcinoma.
AB  - Esophageal carcinoma is among the most common cancers worldwide and a leading
      cause of cancer death [1]. Large numbers of studies indicated that chronic
      inflammation is closely associated with its development [21, 25]. Furthermore,
      the JAK/STAT pathway, which plays a critical role in inflammation and immunity,
      has been implied in a number of malignancies [11]. It has been shown that
      targeting the pathway affected the growth, apoptosis, and metastasis of cultured
      esophageal squamous cell carcinoma cells [26]. We found in the present study that
      STAT3 is constitutively activated in a subgroup of esophageal squamous cell
      carcinoma cell lines and primary tumors. Altered expressions of STAT3 target
      genes were found in these tumors by using RNAseq and qPCR analysis. Cytokines
      that activate STAT3 affected the expression of STAT3 target genes and promoted
      the growth of the ESCC cells, which could be blocked by STAT3 inhibitor and
      specific siRNA. Inhibition of STAT3 also suppressed the growth and colony
      formation, and induced apoptosis in the esophageal squamous cell carcinoma cells
      containing constitutively activated STAT3. Furthermore, the STAT3 inhibitor
      effectively blocked the growth of patient-derived tumor xenografts that harbored
      phosphorylated STAT3, but acted less effective on the xenografts derived from
      primary tumors that contained low levels of activated STAT3. These results
      indicated that activated STAT3 plays a critical role in the survival and growth
      of a subgroup of esophageal squamous cell carcinoma, and may serve as a target
      for precision therapeutic intervention.

PMID- 29179471
TI  - Histone deacetylase 6 inhibition counteracts the epithelial-mesenchymal
      transition of peritoneal mesothelial cells and prevents peritoneal fibrosis.
AB  - The role of histone deacetylase 6 (HDAC6) in peritoneal fibrosis remains unknown.
      In this study, we examined the effect of HDAC6 inhibition on the epithelial
      mesenchymal transition (EMT) of peritoneal mesothelial cells and development of
      peritoneal fibrosis. Treatment with tubastatin A, a highly selective HDAC6
      inhibitor, or silencing of HDAC6 with siRNA inhibited transforming growth factor
      beta1-induced EMT, as evidenced by decreased expression of alpha-smooth muscle
      actin, collagen I and preserved expression of E-cadherin in cultured human
      peritoneal mesothelial cells. In a mouse model of peritoneal fibrosis induced by
      high glucose dialysate, administration of TA prevented thickening of the
      submesothelial region and decreased expression of collagen I and alpha-SMA.
      Mechanistically, tubastatin A treatment inhibited expression of TGF-beta1 and
      phosphorylation of Smad-3, epidermal growth factor receptor, STAT3, and NF
      kappaBp65. HDAC6 inhibition also suppressed production of multiple inflammatory
      cytokines/chemokines and reduced the infiltration of macrophages to the injured
      peritoneum. Moreover, tubastatin A was effective in inhibiting peritoneal
      increase of CD31(+) blood vessels and expression of vascular endothelial growth
      factor in the injured peritoneum. Collectively, these results suggest that HDAC6
      inhibition can attenuate peritoneal fibrosis by inhibiting multiple pro-fibrotic
      signaling pathways, EMT, inflammation and blood vessel formation.

PMID- 29179472
TI  - BCRP expression in schwannoma, plexiform neurofibroma and MPNST.
AB  - Background: peripheral nerve sheath tumors comprise a broad spectrum of
      neoplasms. Vestibular schwannomas and plexiform neurofibromas are symptomatic
      albeit benign, but a subset of the latter pre-malignant lesions will transform to
      malignant peripheral nerve sheath tumors (MPNST). Surgery and radiotherapy are
      the primary strategies to treat these tumors. Intrinsic resistance to drug
      therapy characterizes all three tumor subtypes. The breast cancer resistance
      protein BCRP is a transmembrane efflux transporter considered to play a key role
      in various biological barriers such as the blood brain barrier. At the same time
      it is associated with drug resistance in various tumors. Its potential role in
      drug resistant tumors of the peripheral nervous system is largely unknown.
      Objective: to assess if BCRP is expressed in vestibular schwannomas, plexiform
      neurofibromas and MPNST. Material and methods: immunohistochemical staining for
      BCRP was performed on a tissue microarray composed out of 22 vestibular
      schwannomas, 10 plexiform neurofibromas and 18 MPNSTs. Results: sixteen out of
      twenty-two vestibular schwannomas (73%), nine out of ten plexiform neurofibromas
      (90%) and six out of eighteen MPNST (33%) expressed BCRP in the vasculature.
      Tumor cells were negative. Conclusion: BCRP is present in the vasculature of
      vestibular schwannomas, plexiform neurofibromas and MPSNT. Therefore, it may
      reduce the drug exposure of underlying tumor tissues and potentially cause
      failure of drug therapy.

PMID- 29179473
TI  - A complex microsatellite at chromosome 7q33 as a new prognostic marker of
      colorectal cancer.
AB  - Disease-specific markers are critical for early diagnosis, targeted therapy and
      prognostic prediction of diseases. Current study reports a complex microsatellite
      as a new prognostic marker of sporadic colorectal cancer. This microsatellite
      located at Chromosome 7q33 is composed of three tetranucleotide tandem repeats,
      (TTCC)2(TCCC)5(TCCT)7, flanked by a CT-rich sequence. We analyzed polymorphisms
      of this microsatellite in 158 sporadic colorectal cancer, 143 matched normal
      adjacent tissues (NAT) and 150 health donors. Our results showed that this
      complex microsatellite was instable with polymorphic frequency of 77.2% in
      colorectal cancer, 52.4% in NAT and 54.7% in health donors (p<0.01) when compared
      to reference sequence. In the three tandem repeats, (TCCT)7 site was most
      polymorphic accounting for over 70.0% of polymorphisms in this complex
      microsatellite, followed by (TTCC)2 site for approximately 20%. Polymorphisms in
      (TCCC)5 was rare. Polymorphisms at the (TCCT)7 site were mainly insertions of 1
      to 4 copies of TCCT (88.6%), and deletions occurred in about 6.4% of cases. The
      (TTCC)2 site was featured with one copy TTCC insertions. Pair-wise analyses
      between colorectal tumors and NAT revealed that 88 of 121 (72.7%) tumors
      displayed expansion, contraction or both in these tetranucleotide tandem repeats
      when compared to NAT. A cross-analysis with clinicopathological data of 158
      colorectal cancers revealed that polymorphic alterations of the microsatellite
      associated with less lymphatic metastasis (p<0.001), and the colorectal cancer
      patients with polymorphic changes in this microsatellite demonstrated better
      survival (n=112, p=0.0058). Together these data suggest that this complex
      microsatellite is a potential prognostic marker of sporadic colorectal cancer.

PMID- 29179474
TI  - Lung cancer mortality clusters in Shandong Province, China: how do they change
      over 40 years?
AB  - Lung cancer has long been a major health problem in China. This study aimed to
      examine the temporal trend and spatial pattern of lung cancer mortality in
      Shandong Province from 1970 to 2013. Lung cancer mortality data were obtained
      from Shandong Death Registration System and three nationwide retrospective cause
      of-death surveys. A Purely Spatial Scan Statistics method with Discrete Poisson
      models was used to detect possible high-risk spatial clusters. The results show
      that lung cancer mortality rate in Shandong Province increased markedly from 1970
      1974 (7.22 per 100,000 person-years) to 2011-2013 (56.37/100, 000). This increase
      was associated with both demographic and non-demographic factors. Several
      significant spatial clusters with high lung cancer mortality were identified. The
      most likely cluster was located in the northern region of Shandong Province
      during both 1970-1974 and 2011-2013. It appears the spatial pattern remained
      largely consistent over the last 40 years despite the absolute increase in the
      mortality rates. These findings will help develop intervention strategies to
      reduce lung cancer mortality in this large Chinese population.

PMID- 29179475
TI  - Genetic variants in the inflammation pathway as predictors of recurrence and
      progression in non-muscle invasive bladder cancer treated with Bacillus Calmette
      Guerin.
AB  - : Inflammation plays a critical role in the etiology of several cancers and may
      affect their clinical outcome. Our objective was to assess the association of
      genetic variants within the inflammation pathway with recurrence and progression
      among non-muscle invasive bladder cancer (NMIBC) patients with or without
      Bacillus Calmette-Guerin (BCG) treatment. We genotyped 372 single nucleotide
      polymorphisms (SNPs) in 27 selected genes within the inflammation pathway in 349
      patients diagnosed with NMIBC, followed by internal validation in 322 additional
      patients. We used Cox proportional hazards regression analyses to identify SNPs
      as predictors for recurrence and progression. In the discovery phase, we
      identified 20 variants that were significantly associated with recurrence
      outcomes and 15 SNPs significantly associated with progression in patients
      treated with BCG but not in the transurethral resection (TUR)-only group. In BCG
      treated patients, rs7089861 was the only SNP significantly associated with risk
      of progression in both the discovery phase (Hazard Ratio [HR]=3.15, 95%
      Confidence Interval [CI]: 1.38-7.22, P<0.01) and validation phase (HR=3.84, 95%
      CI: 1.64-9.0, P=0.002; meta-analysis HR=3.47, 95% CI: 1.92-6.28, P<0.001). Two
      variants, rs1800686 and rs2071081, had probable association with HRs of the same
      trend in the discovery and validation groups (meta-analysis P=0.002). These
      findings supported the notion that genetic variation of inflammation pathway may
      impact clinical outcome of NMIBC patients treated with BCG immunotherapy. Further
      validation of these results in order to improve risk stratification to identify
      patients most likely to benefit from BCG treatment versus upfront radical
      cystectomy and future development of potential targeted therapies are warranted.
      Significance Statement: In a two-stage study, we identified several genetic
      variants in the inflammation pathway associated with recurrence and progression
      in early-stage bladder cancer. In particular, variant rs7089861 was validated for
      progression among patients who underwent BCG immunotherapy. Several other
      variants showed marginal association with recurrence or progression. These
      findings suggest that inflammatory pathway genetic variants may influence
      clinical outcome of bladder cancer patients and help to select patients most
      appropriate for BCG treatment.

PMID- 29179476
TI  - Hyperoside alleviates adriamycin-induced podocyte injury via inhibiting
      mitochondrial fission.
AB  - Podocyte injury underlies many forms of glomerular diseases. Our previous study
      showed that hyperoside, a naturally occurring flavonoid, could decrease
      albuminuria at the early stage of diabetic nephropathy by ameliorating renal
      damage and podocyte injury. However, its protective mechanism against podocyte
      injury is unknown. A previous study demonstrated that hyperoside might inhibit
      amyloid beta-protein-induced neurotoxicity by suppressing mitochondrial
      dysfunction. Both mitochondrial dysfunction and its upstream determinant
      mitochondrial fission were closely related to podocyte injury. Thus, in the
      current study, we tested the effect of hyperoside on mitochondrial dysfunction
      and mitochondrial fission in adriamycin (ADR)-induced podocyte injury. In the
      mice model of ADR-induced nephropathy, hyperoside treatment inhibited ADR-induced
      albuminuria and podocyte injury. Meanwhile, hyperoside also blocked ADR-induced
      mitochondrial dysfunction and mitochondrial fission. Consistently, in cultured
      human podocytes, hyperoside suppressed ADR-induced podocyte injury, mitochondrial
      dysfunction and mitochondrial fission. All these results indicated that
      hyperoside might inhibit ADR-induced mitochondrial dysfunction and podocyte
      injury through suppressing mitochondrial fission both in vivo and in vitro. The
      underlying mechanisms which we revealed support the therapeutic effects of
      hyperoside for a broad range of glomerular diseases.

PMID- 29179477
TI  - Long noncoding RNA NNT-AS1 promotes hepatocellular carcinoma progression and
      metastasis through miR-363/CDK6 axis.
AB  - Long non-coding RNAs (lncRNAs) have been tested to act as important regulator in
      liver cancer genesis and progression. LncRNA Nicotinamide Nucleotide
      Transhydrogenase-antisense RNA1 (NNT-AS1) has been reported to participate in the
      tumorigenesis. However, the exact molecular mechanism of NNT-AS1 in
      hepatocellular carcinoma (HCC) is still unknown. In present study, our team
      identified the up-regulated expression of NNT-AS1 in HCC tissue and cell lines
      compared with adjacent noncancerous tissue and normal cells. Moreover, HCC
      patients with high NNT-AS1 levels had poor prognosis than that with low NNT-AS1
      level (p=0.0089). In vitro, gain- and loss-of-function experiments revealed that
      enhanced NNT-AS1 expression promoted the proliferation ability and alleviated the
      cycle arrest and apoptosis, while NNT-AS1 knockdown suppressed the proliferation
      and induced G0/G1 phase arrest and apoptosis. In vivo, NNT-AS1 knockdown
      inhibited the HCC neoplastic tumor volume and weight. Bioinformatics analysis and
      luciferase reporter assay validated that miR-363 targeted NNT-AS1 and CDK6 3'
      UTR. MiR-363 was down-regulated in HCC tissue and cells. NNT-AS1 competed with
      CDK6 for miR-363 binding and could increase CDK6 expression. In summary, our
      results suggest the oncogenic role of NNT-AS1 in HCC tumorigenesis through miR
      363/CDK6 axis, providing a novel therapeutic target for human HCC.

PMID- 29179478
TI  - 64Cu-ATSM internal radiotherapy to treat tumors with bevacizumab-induced vascular
      decrease and hypoxia in human colon carcinoma xenografts.
AB  - Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is an
      antiangiogenic agent clinically used for various cancers. However, repeated use
      of this agent leads to tumor-decreased vascularity and hypoxia with activation of
      an HIF-1 signaling pathway, which results in drug delivery deficiency and
      induction of malignant behaviors in tumors. Here, we developed a novel strategy
      to treat tumors with bevacizumab-induced vascular decrease and hypoxia using 64Cu
      diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), a potential theranostic
      agent, which possesses high tissue permeability and can target over-reduced
      conditions under hypoxia in tumors, with a human colon carcinoma HT-29 tumor
      bearing mouse model. The long-term treatment with bevacizumab caused decreased
      blood vessel density and activation of an HIF-1 signaling pathway; increased
      uptake of 64Cu-ATSM was also observed despite limited blood vessel density in HT
      29 tumors. In vivo high-resolution SPECT/PET/CT imaging confirmed reduced
      vascularity and increased proportion of 64Cu-ATSM uptake areas within the
      bevacizumab-treated tumors. 64Cu-ATSM therapy was effective to inhibit tumor
      growth and prolong survival of the bevacizumab-treated tumor-bearing mice without
      major adverse effects. In conclusion, 64Cu-ATSM therapy effectively enhanced anti
      tumor effects in tumors with bevacizumab-induced vascular decrease and hypoxia.
      64Cu-ATSM therapy could represent a novel approach as an add-on to antiangiogenic
      therapy.

PMID- 29179479
TI  - Splenectomy is associated with an aggressive tumor growth pattern and altered
      host immunity in an orthotopic syngeneic murine pancreatic cancer model.
AB  - The purpose of this study was to investigate whether splenectomy influences the
      tumor growth and metastatic pattern in an orthotopic syngeneic murine pancreatic
      cancer model. Murine pancreatic cancer cells (PAN02) were subcutaneously injected
      into the flanks of nude mice. A small tumor fragment (3 mm2), harvested from a
      subcutaneous tumor. was orthotopically implanted in the tail of the pancreas of
      C57/BL6 mice without splenectomy (control group, n=15) or with simultaneous
      splenectomy (splenectomy group, n=15). Tumor growth and metastatic patterns were
      analyzed by laparotomy at 21 days after surgery. No tumor growth was found in 5
      mice (33.3%) of the control group and 1 mouse (6.7%) of the splenectomy group
      (p=0.169). Tumor volume was significantly larger in splenectomy group (p=0.013).
      Peritoneal seeding was more frequently observed in the splenectomy group (11
      (73.3%) vs. 4 (26.7%), p=0.011). There were no differences in the number of liver
      and kidney metastasis between the two groups. The ratios of tumor-infiltrating
      CD4+ to FoxP3+ and CD8+ to FoxP3+ were significantly higher in the control group
      compared to the splenectomy group (8.2 +/- 9.3 vs. 2.4 +/- 1.5, p=0.046; 2.5 +/-
      1.4 vs. 1.5 +/- 0.4, p=0.031, respectively). Splenectomy enhanced tumor growth
      and peritoneal seeding in an orthotopic syngeneic murine pancreatic cancer mouse
      model. The ramification of these results are discussed for pancreatic cancer
      treatment.

PMID- 29179481
TI  - Notochordal-cell derived extracellular vesicles exert regenerative effects on
      canine and human nucleus pulposus cells.
AB  - During intervertebral disc ageing, chondrocyte-like cells (CLCs) replace
      notochordal cells (NCs). NCs have been shown to induce regenerative effects in
      CLCs. Since vesicles released by NCs may be responsible for these effects, we
      characterized NC-derived extracellular vesicles (EVs) and determined their effect
      on CLCs. EVs were purified from porcine NC-conditioned medium (NCCM) through size
      exclusion chromatography, ultracentrifugation or density gradient centrifugation.
      Additionally, the EVs were quantitatively analyzed by high-resolution flow
      cytometry. The effect of NCCM-derived EVs was studied on canine and human CLC
      micro-aggregates in vitro and compared with NCCM-derived proteins and
      unfractionated NCCM. Porcine NCCM contained a considerable amount of EVs. NCCM
      derived EVs induced GAG deposition in canine CLCs to a comparable level as NCCM
      derived proteins and unfractionated NCCM, and increased the DNA and
      glycosaminoglycan (GAG) content of human micro-aggregates, although to a lesser
      extent than unfractionated NCCM. The biological EV effects were not considerably
      influenced by ultracentrifugation compared with size exclusion-based
      purification. Upon ultracentrifugation, interfering GAGs, but not collagens, were
      lost. Nonetheless, collagen type I or II supplemented to CLCs in a concentration
      as present in NCCM induced no anabolic effects. Porcine NCCM-derived EVs exerted
      anabolic effects comparable to NCCM-derived proteins, while unfractionated NCCM
      was more potent in human CLCs. GAGs and collagens appeared not to mediate the
      regenerative EV effects. Thus, NC-derived EVs have regenerative potential, and
      their effects may be influenced by the proteins present in NCCM. The optimal
      combination of NC-secreted factors needs to be determined to fully exploit the
      regenerative potential of NC-based technology.

PMID- 29179480
TI  - Neutrophil/lymphocyte ratio is a more sensitive systemic inflammatory response
      biomarker than platelet/lymphocyte ratio in the prognosis evaluation of
      unresectable pancreatic cancer.
AB  - Multiple cancers arise from sites of infection, chronic irritation, and
      inflammation. It has been widely accepted that pancreatic cancer is an
      inflammation-driven cancer. In this study, we investigated the application value
      of systemic inflammatory markers, neutrophil to lymphocyte ratio (NLR) and
      platelet to lymphocyte ratio (PLR), in the prediction of chemotherapy response
      and prognosis in patients with late pancreatic cancer. 122 patients with
      inoperable pancreatic cancers were included and separated into two groups
      according to median values of NLR or PLR (NLR low:<3.81 or NLR high:>=3.81, and
      PLR low:<142.14 or PLR high>=142.14, respectively). Baseline NLR and PLR levels
      were significantly higher in pancreatic cancer patients compared with the healthy
      subjects. Neither of the baseline NLR or PLR levels could predict outcomes.
      Patients with low baseline level of NLR, but not PLR, had better responses to
      chemotherapy. Changes in NLR, but not PLR levels, were associated with the
      therapeutic efficacy. Patients who stayed in or dropped into the low NLR level
      subgroup after first-line chemotherapy had better responses, comparing to those
      stayed in or jumped into the high NLR level group. No similar results could be
      observed when the PLR level was investigated. Therefore, NLR is a more sensitive
      biomarker than PLR in the prediction of chemotherapy response of patients.

PMID- 29179482
TI  - Association of fibroblast growth factor receptor 1 gene amplification with poor
      survival in patients with esophageal squamous cell carcinoma.
AB  - Purpose: To investigate whether FGFR1 gene amplification is associated with
      clinicopathologic characteristics and its potential impact on survival in
      patients with resected esophageal squamous cell carcinoma (ESCC). Methods: Five
      hundred fifty-six ESCC patients undergoing curative resection of ESCC were
      retrospectively studied. FGFR1 gene copy number was determined in microarrayed
      tumor samples using fluorescent in situ hybridization (FISH) analysis. FGFR1 gene
      amplification status was prespecified as copy number >= 6 or FGFR1/CEN 8 ratio >=
      2.2. FGFR1 expression was evaluated by immunohistochemistry. Overall survival
      (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method
      followed by the log rank test. Correlation with survival was examined using
      multivariate Cox regression. Results: FGFR1 amplification was identified in 67
      (12.1%) patients; these patients had significantly shorter OS (50.0 vs 32.0
      months; log rank; P<0.001) as well as shorter DFS (47.0 vs 28.0 months; log rank;
      P<0.001) than those without FGFR1 amplification. Under a Cox proportional hazard
      model, FGFR1 amplification was associated with significantly shorter OS (adjusted
      hazard ratio [AHR]=1.61; 95% CI, 1.10-2.43, P=0.004) and DFS (AHR=1.72; 95%CI,
      1.15-2.48; P<0.001). Moreover, cases with high intratumoral FGFR1 expression
      showed significantly shorter OS and DFS than those with low FGFR1 expression. The
      frequency of FGFR1 amplification was significantly higher in heavy drinkers than
      in moderate and light drinkers. Conclusion: FGFR1 amplification is an independent
      adverse prognostic factor in surgically resected ESCC. FGFR1 may be a promising
      therapeutic target in patients with ESCC.

PMID- 29179483
TI  - MicroRNA-216a inhibits the metastasis of gastric cancer cells by targeting
      JAK2/STAT3-mediated EMT process.
AB  - MicroRNAs (miRNAs), a group of small, non-protein coding, endogenous RNAs, play
      critical roles in the tumorigenesis and progression of human cancer. miR-216a has
      recently been reported to play an oncogenic role in human cancer. While, the
      expression of miR-216a, its biological function and underlying molecular
      mechanisms in gastric cancer (GC) are largely unknown. In this study, we revealed
      that miR-216a was underexpressed in GC tissues compared to matched noncancerous
      tissues. Decreased levels of miR-216a were confirmed in GC cell lines compared
      with a normal gastric epithelium cell line. miR-216a underexpression was
      associated with malignant prognostic features including lymph node metastasis,
      venous infiltration, invasive depth and advanced TNM stage. GC patients with low
      miR-216a level showed an obvious shorter overall survival. miR-216a
      overexpression restrained migration and invasion of MGC-803 cells, while its
      knockdown exerted opposite effects on metastatic behaviors of SGC-7901 cells. In
      vivo experiments found that miR-216a restoration reduced metastatic nodes of GC
      cells in nude mice liver. miR-216a notably suppressed epithelial-mesenchymal
      transition (EMT) of GC cells. Janus kinase 2 (JAK2) was recognized as a direct
      target and downstream mediator of miR-216a in GC cells. Interestingly,
      JAK2/signal transducer and activator of transcription 3 (STAT3) pathway was
      prominently inactivated by miR-216a and probably mediated the role of miR-216a in
      the regulation of migration, invasion and EMT process of GC cells. In conclusion,
      these data suggest that miR-216a functions as a tumor suppressive miRNA in the
      development of GC possibly by targeting JAK2/STAT3-mediated EMT.

PMID- 29179484
TI  - Association of circulating branched-chain amino acids with cardiometabolic traits
      differs between adults and the oldest-old.
AB  - Branched-chain amino acids (BCAAs) are promising for their potential anti-aging
      effects. However, findings in adults suggest that circulating BCAAs are
      associated with cardiometabolic risk. Moreover, little information is available
      about how BCAAs influence clustered cardiometabolic traits in the oldest-old (>85
      years), which are the fastest-growing segment of the population in developed
      countries. Here, we applied a targeted metabolomics approach to measure serum
      BCAAs in Chinese participants (aged 21-110 years) based on a longevity cohort.
      The differences of quantitative and dichotomous cardiometabolic traits were
      compared across BCAAs tertiles. A generalized additive model (GAM) was used to
      explore the dose-response relationship between BCAAs and the risk of metabolic
      syndrome (MetS). Overall, BCAAs were correlated with most of the examined
      cardiometabolic traits. The odds ratios for MetS across the increasing BCAA
      tertiles were 3.22 (1.70 - 6.12) and 5.27 (2.88 - 9.94, referenced to tertile 1)
      after adjusting for age and gender (Ptrend < 0.001). The association still
      existed after further controlling for lifestyle factors and inflammation factors.
      However, the correlations between circulating BCAAs and quantitative traits were
      weakened in the oldest-old, except for lipids, the levels of which were
      distinctly different from those in adults. The stratified analysis also suggested
      that the risky BCAAs-MetS association was more pronounced in adults than in the
      oldest-old. Moreover, generalized additive model (GAM)-based curve-fitting
      suggested that only when BCAAs exceeded a threshold (approximately 450 MUmol/L)
      was the BCAAs-MetS association significant. The relationship might be aging
      dependent and was more pronounced in adults than in the oldest-old.

PMID- 29179485
TI  - Cost-effectiveness analysis of fecal microbiota transplantation for inflammatory
      bowel disease.
AB  - There is a lack of health economics evidence on the use of fecal microbiota
      transplantation (FMT) for inflammatory bowel disease (IBD). This study aims to
      evaluate the cost-effectiveness before (with conventional therapy) and after
      introducing FMT for treating IBD. 104 patients with IBD received FMT were
      recruited. Health status was evaluated by European dimension health table (ED
      5Q). Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NB)
      were calculated by different age groups, genders, smoking status, and disease
      subtypes. The willingness-to-pay threshold was set to the value equal to three
      times China's per capita GDP (141240 CNY/QALY, 2014). From the health-care
      perspective, FMT strategy was 73% likely to be cost-effective compared with the
      conventional therapy before FMT with an ICER of -185712 CNY/QALY and a positive
      NB of CNY 45150. From the societal perspective, FMT strategy was 75% likely to be
      cost-effective with an ICER of -207417 CNY/QALY and a positive NB of CNY 48395.
      Moreover, younger patients (<= 24), females, non-smokers and Crohn's disease (CD)
      achieved more benefits. This study for the first time demonstrated that FMT
      showed its cost-effectiveness, especially on improving the life quality and
      decreasing the medical and societal cost, for the moderate to severe IBD in a
      Chinese cohort.

PMID- 29179486
TI  - Functional expression of Tim-3 on blasts and clinical impact of its ligand
      galectin-9 in myelodysplastic syndromes.
AB  - T-cell immunoglobulin mucin-3 (Tim-3), an inhibitory immune checkpoint receptor,
      is highly expressed on acute myeloid leukemia cells and its ligand galectin-9 is
      reported to drive leukemic progression by binding with Tim-3. However, it remains
      unclear whether the Tim-3-galectin-9 pathway is associated with the
      pathophysiology of myelodysplastic syndromes (MDS). Thus, we investigated the
      expression and function of Tim-3 and the clinical impact of its ligand galectin-9
      in MDS. Tim-3 expression levels on MDS blasts by CD45/side-scatter or CD34/CD45
      gating were increased as MDS progressed to the advanced stage. Tim-3 expression
      in the MDS blasts was upregulated in the presence of the cell culture supernatant
      of human stromal cells or the MDS-related cytokine transforming growth factor
      beta1. The proliferation of Tim-3+ MDS blasts was inhibited by the blockade of
      anti-Tim-3 antibody. Furthermore, plasma levels of galectin-9 were elevated as
      MDS progressed to the advanced stage in 70 MDS/acute leukemia transformed from
      MDS patients and was a prognostic factor in 40 MDS patients. Our data
      demonstrated that the Tim-3-galectin-9 pathway is associated with the
      pathogenesis and disease progression of MDS. These findings provide new insight
      into potential immunotherapy targeting the galectin-9-Tim-3 pathway in MDS.

PMID- 29179487
TI  - PARP-1 promotes tumor recurrence after warm ischemic liver graft transplantation
      via neutrophil recruitment and polarization.
AB  - Poly (ADP-ribose) polymerase 1 (PARP-1) is a crucial contributor to exacerbate
      ischemia and reperfusion (IR) injury and cancer process. However, there is little
      research into whether PARP-1 affects the hepatocellular carcinoma (HCC)
      recurrence after liver transplantation. In this study, we investigated the
      influence of PARP-1 on hepatic neutrophil mobilizing and phenotype shifting which
      may lead to HCC recurrence after liver transplantation. We found that rats
      received the grafts with warm ischemic injury had higher risk of HCC recurrence,
      which was markedly prevented by pharmacological inhibition of PARP-1 after liver
      transplantation. In mouse models, the up-regulation of PARP-1 was closely related
      to the greater tumor burden and increased hepatic susceptibility to recurrence
      after IR injury. The reason was that high hepatic PARP-1 led to increased liver
      CXCL1 levels, which in turn promoted recruitment of neutrophils. Both blocking
      CXCL1/CXCR2 signaling pathway and depleting neutrophils decreased tumor burden.
      Moreover, these infiltrating neutrophils were programmed to a proangiogenic
      phenotype under the influence of PARP-1 in vivo after hepatic IR injury. In
      conclusion, IR-induced PARP-1 up-regulation increased the hepatic recruitment of
      neutrophils through regulation of CXCL1/CXCR2 signaling and polarized hepatic
      neutrophils to proangiogenic phenotype, which further promoted HCC recurrence
      after transplantation.

PMID- 29179488
TI  - Forensic efficiency and genetic variation of 30 InDels in Vietnamese and Nigerian
      populations.
AB  - Insertion/deletion polymorphisms (InDels) are ubiquitous diallelic genetic
      markers that have drawn increasing attention from forensic researchers. Here, we
      investigated 30 InDel loci in Vietnamese and Nigerian populations and evaluated
      their usefulness in forensic genetics. The polymorphic information content of
      these populations ranged, respectively, from 0.164 to 0.375 and from 0.090 to
      0.375 across loci. After Bonferroni correction, no significant deviation from
      Hardy-Weinberg equilibrium was found, except for HLD97 in the Nigerian
      population. The cumulative power of exclusion for all 30 loci in the Vietnamese
      and Nigerian populations was 0.9870 and 0.9676, respectively, indicating that
      this InDel set is not suitable for paternity testing in these populations, but
      could be included as a supplement. For the Vietnamese and the Nigerian
      populations, the mean observed heterozygosity was 0.5917 and 0.6268, and the
      combined discrimination power of the 30 loci was 0.9999999999767 and
      0.9999999999603, respectively. These findings indicated that these InDels may be
      suitable for personal forensic identification in the studied populations. The
      results of DA distance, phylogenetic tree, principal component, and cluster
      analyses were consistent and indicated a clear pattern of regional distribution.
      Moreover, the Vietnamese population was shown to have close genetic relationships
      with the Guangdong Han and Shanghai Han populations.

PMID- 29179489
TI  - Saikosaponin A inhibits IL-1beta-induced inflammatory mediators in human
      osteoarthritis chondrocytes by activating LXRalpha.
AB  - Saikosaponin a (SSa), one of the main active components of Bupleurum falcatum,
      has been reported to have anti-inflammatory effect. In the present study, we
      investigated the anti-inflammatory effect of SSa on IL-1beta-stimulated human
      osteoarthritis chondrocytes. The cells were pretreated with SSa 12 h before IL
      1beta treatment. The production of PGE2 and NO were detected by ELISA and Griess
      method. The levels of MMP1, MMP3, and MMP13 were measured by ELISA and qRT-PCR.
      The expression of NF-kappaB and LXRalpha were tested by western blot analysis.
      The results showed that SSa inhibited IL-1beta-induced PGE2 and NO production in
      a concentration-dependent manner. SSa also suppressed IL-1beta-induced MMP1,
      MMP3, and MMP13 production. Furthermore, SSa significantly attenuated IL-1beta
      induced phosphorylation levels of NF-kappaB p65 and IkappaBalpha. SSa also up
      regulated the expression of LXRalpha. The inhibition of SSa on PGE2, NO, MMP1,
      MMP3, and MMP13 production were reversed by LXRalpha siRNA or GGPP, the inhibitor
      of LXRalpha. In conclusion, our results demonstrated that SSa inhibited
      inflammatory responses in human chondrocytes in vitro. SSa might be a potential
      therapeutic drug for osteoarthritis.

PMID- 29179490
TI  - Proteome-based identification of apolipoprotein A-IV as an early diagnostic
      biomarker in liver fibrosis.
AB  - Hepatic fibrosis may ultimately result in organ failure and death, a reality
      compounded by the fact that most drugs for liver fibrosis appear to be effective
      only if given as a prophylactic or early treatment. In a dimethylnitrosamine
      induced liver fibrotic model, aspartate aminotransferase/alanine aminotransferase
      levels could not precisely distinguish the differences between the initial stage
      of liver fibrosis and normal control, whereas histological examination indicated
      that dimethylnitrosamine treatment for two weeks has resulted in hepatic
      fibrogenesis. Comprehensive proteomics identified 12 proteins mainly associated
      with the interleukin 6-stimulated inflammatory pathway. Coordinately, cytokine
      profiles showed that dimethylnitrosamine administration would stimulate various
      signaling pathways leading to liver fibrosis. Of note, apolipoprotein A4 in serum
      samples obtained from patients in the early stage of liver fibrosis were
      significantly increased compared to the healthy controls (p<0.001) while the area
      under curve was 0.966. Moreover, increased apolipoprotein A4 significantly
      enhanced transforming growth factor beta 1-induced alpha smooth muscle actin
      expression. In this regard, overexpression of apolipoprotein A4 in early stage of
      liver fibrosis might magnify and imply the progression of hepatic fibrosis. These
      findings suggest that apolipoprotein A4 upregulation may correlate with hepatic
      fibrosis staging and that apolipoprotein A4 together with current biomarker can
      increase the sensitivity and specificity for the early detection of liver
      fibrosis in a high-throughput manner.

PMID- 29179491
TI  - SIRT1 promotes tumor-like invasion of fibroblast-like synoviocytes in rheumatoid
      arthritis via targeting TIMP1.
AB  - Suppression of tissue inhibitor of matrix metalloproteinase (TIMP) is associated
      with the tumor-like invasion of fibroblast-like synoviocytes (FLSs) that occurs
      during rheumatoid arthritis-related cartilage destruction. Silent information
      regulator 2 homolog1 (SIRT1), a histone deacetylase, is widely involved in
      transcriptional regulation, genomic stability, metabolism and DNA repair. Recent
      studies suggest that SIRT1 may also impact inflammatory response and the
      proliferation of FLSs in rheumatoid arthritis (RA). However, it is unknown
      whether SIRT1 has a role in the tumor-like invasion of FLSs in rheumatoid
      arthritis. Herein we report that SIRT1 contributes to FLS invasion and cartilage
      destruction via a TIMP1-dependent mechanism. Elevated SIRT1 in RA synovia
      suppresses TIMP1 expression via deacetylation of TIMP1-associated histones,
      thereby disrupting the binding of the transcription factor specificity protein 1
      (Sp1) to the TIMP1 promoter. In rats with collagen-induced arthritis, depletion
      of SIRT1 remarkably promoted TIMP1 expression in synovial tissues and ameliorated
      cartilage destruction. These results describe a new role for SIRT1 and
      demonstrate its potential value as a therapeutic target for rheumatoid arthritis.

PMID- 29179492
TI  - Identification of a gene signature associated with radiotherapy and prognosis in
      gliomas.
AB  - Glioma is one of the most common primary brain tumors with poor prognosis.
      Although radiotherapy is an important treatment method for gliomas, the efficacy
      is still limited by the high occurrence of radioresistance and the underlying
      molecular mechanism is unclear. Here, we performed a data mining work based on
      four glioma expression datasets. These datasets were classified into training set
      and validation set. Radiotherapy-induced differential expressed genes and
      prognosis-associated genes were screened using different classifiers. The Kaplan
      Meier curves along with the two-sided Log Rank (Mantel-Cox) test were used to
      evaluate overall survival. We found the gene expression profiles of gliomas
      between those patients received radiotherapy and those patients without received
      radiotherapy were quite different. A 20-gene signature was identified, which was
      associated with radiotherapy.Furthermore, a novel 5-gene signature (HOXC10,
      LOC101928747, CYB561D2, RPL36A and RPS4XP2) as an independent predictor of glioma
      patients' prognosis was further derived from the 20-gene signature. These
      findings provided a new insight into the molecular mechanism of radioresistance
      in gliomas. The 5-gene signature might represent therapeutic target for gliomas.

PMID- 29179493
TI  - Sphingosine kinase 1 mediates diabetic renal fibrosis via NF-kappaB signaling
      pathway: involvement of CK2alpha.
AB  - Sphingosine kinase 1 (SphK1) plays a pivotal role in regulating diabetic renal
      fibrotic factors such as fibronectin (FN) and intercellular adhesion molecule-1
      (ICAM-1). Especially, activation of SphK1 is closely linked to the body
      inflammatory reaction. Casein kinase 2alpha subunit (CK2alpha), a protein kinase
      related to inflammatory reaction, influences diabetic renal fibrosis and
      expressions of FN and ICAM-1 via NF-kappaB pathway. However, the mechanism by
      which SphK1 mediates diabetic renal fibrosis has not yet fully elucidated. The
      current study is aimed to investigate if SphK1 mediates diabetic renal fibrotic
      pathological process via inflammatory pathway and activation of CK2alpha. The
      following findings were observed: (1) Expressions of SphK1 were upregulated in
      kidneys of diabetic mice and rats; (2) Knockdown of SphK1 expression suppressed
      high glucose (HG)-induced NF-kappaB nuclear translocation and expressions of FN
      and ICAM-1; (3) Compared with C57 diabetic mice, SphK1-/- diabetic mice exhibited
      less renal fibrotic lesions, FN accumulation and NF-kappaB nuclear accumulation
      in glomeruli of kidneys; (4) SphK1 mediated phosphorylation of CK2alpha, while
      CK2alpha knockdown depressed SphK1-induced activation of NF-kappaB pathway. This
      study indicates the essential role of SphK1 in regulating activation of CK2alpha
      and diabetic renal fibrotic pathological process via NF-kappaB.

PMID- 29179494
TI  - Combinatorial effects of an epigenetic inhibitor and ionizing radiation
      contribute to targeted elimination of pancreatic cancer stem cell.
AB  - Pancreatic cancer is associated with a high mortality rate, owing to de novo and
      acquired drug resistance, thereby leading to highly invasive and metastatic
      pancreatic cancer cells. Therefore, targeting pancreatic cancer stem cells (CSCs)
      may be a novel therapeutic strategy for the treatment of pancreatic cancer. Here,
      we combined a DNA methylation inhibitor (5-aza-2'-deoxycytidine; 5-aza-dC) and
      ionizing radiation (IR) to improve anti-cancer effects by inhibiting growth and
      proliferation and promoting apoptosis of pancreatic cancer cells in vitro and in
      vivo. Importantly, the combinatorial effect of 5-aza-dC with IR on sphere-forming
      pancreatic cancer cells was preferentially targeted toward CSCs through the
      downregulation of regulatory factors of self-renewal and CSC surface markers. We
      next performed the RNA sequencing to understand the underlying cellular
      mechanisms of the combined treatment with IR and 5-aza-dC in pancreatic cancer
      cells. Global transcriptome profiling indicated that the expression of the Oct4
      centered transcriptional network of genes was significantly downregulated in
      cells with combination treatment. Our data suggested that combination treatment
      with DNA methylation inhibitor and IR may be a novel therapeutic strategy for
      pancreatic cancer. Overall, these findings support the use of epigenetic therapy
      in combination with radiotherapy to improve therapeutic efficacy by targeting and
      eradicating pancreatic CSCs.

PMID- 29179495
TI  - ndmaSNF: cancer subtype discovery based on integrative framework assisted by
      network diffusion model.
AB  - Recently, with the rapid progress of high-throughput sequencing technology,
      diverse genomic data are easy to be obtained. To effectively exploit the value of
      those data, integrative methods are urgently needed. In this paper, based on SNF
      (Similarity Network Diffusion) [1], we proposed a new integrative method named
      ndmaSNF (network diffusion model assisted SNF), which can be used for cancer
      subtype discovery with the advantage of making use of somatic mutation data and
      other discrete data. Firstly, we incorporate network diffusion model on mutation
      data to make it smoothed and adaptive. Then, the mutation data along with other
      data types are utilized in the SNF framework by constructing patient-by-patient
      similarity networks for each data type. Finally, a fused patient network
      containing all the information from different input data types is obtained by
      using a nonlinear iterative method. The fused network can be used for cancer
      subtype discovery through the clustering algorithm. Experimental results on four
      cancer datasets showed that our ndmaSNF method can find subtypes with significant
      differences in the survival profile and other clinical features.

PMID- 29179496
TI  - Prognostic role of myoferlin expression in patients with clear cell renal cell
      carcinoma.
AB  - Objectives: In patients with cancer, myoferlin protein hyperexpression has been
      correlated with poor patient prognosis. Here, we evaluated myoferlin expression
      in patients with clear cell renal cell carcinoma (ccRCC) and investigated the
      prognostic significance of myoferlin expression in these patients. Materials and
      Methods: One hundred and fifty-two patients with ccRCC who underwent treatment at
      Gyeongsang National University Hospital, Korea, between January 2000 and December
      2009 were enrolled. Immunohistochemical analysis was performed on tissue
      microarray blocks produced from surgical specimens. Surgical specimen cancerous
      cells were graded as showing myoferlin hyperexpression or hypoexpression by
      comparison with intratumoral endothelial cells. Disease-free survival was
      evaluated using Kaplan-Meier analysis. Cox regression analysis was used to
      determine the relationships between myoferlin expression levels, risk factors,
      and prognosis. Results: Seventy-one of 304 cores exhibited myoferlin
      hyperexpression. T stage was not associated with myoferlin hyperexpression,
      whereas a high Fuhrman nuclear grade was significantly associated with myoferlin
      hyperexpression. Kaplan-Meier analysis revealed that patients with T stage >2,
      Fuhrman nuclear grade >2, and those with myoferlin hyperexpression had poorer
      disease-free survival compared to those with lower T stage, lower Fuhrman nuclear
      grade, and myoferlin hypoexpression (all p <0.001). Furthermore, myoferlin
      hyperexpression was significantly associated with disease-free survival on Cox
      regression analysis (hazard ratio, 4.604; 95% confidence interval, 1.893-11.199;
      p = 0.001). Conclusion: Myoferlin expression could be a potential prognosticator
      in patients with ccRCC, and might be a useful marker for oncologic surveillance
      in such patients.

PMID- 29179497
TI  - Marital status and survival in epithelial ovarian cancer patients: a SEER-based
      study.
AB  - Marital status has been proved to be correlated to the survival of patients in
      various cancer types, except for that in the large female population of
      epithelial ovarian cancer (EOC). In this study, we retrospectively extracted
      10905 eligible EOC patients from the Surveillance, Epidemiology, and End Results
      (SEER) database in the period from 2004 to 2012. We categorized marital status as
      married, divorced/separated, widowed, and never married. Chi-square test was used
      to investigate the association between marital status and other variables. The
      Kaplan-Meier test was adopted to compare survival curves of different groups.
      Multivariate Cox regression analyses were conducted to estimate the effect of
      marital status on overall survival (OS) and epithelial ovarian cancer-specific
      survival (EOCSS). To explore how marital status affected patients diagnosed at
      the same stage, we further performed subgroup analyses according to TNM stage.
      The results showed that marital status was an independent predictor for OS and
      EOCSS. Subgroup analyses indicated that the relationship between marital status
      and prognosis varied according to different conditions. Widowed patients had
      poorer prognosis than the other groups in most conditions, while the never
      married group showed similar risk of mortality as the married ones.

PMID- 29179498
TI  - ACAT-1 gene polymorphism is associated with increased susceptibility to coronary
      artery disease in Chinese Han population: a case-control study.
AB  - Several studies suggest an important role of Acyl-CoA: cholesterol
      acyltransferase-1(ACAT-1) in the development of atherosclerosis. The aim of
      present study was to investigate whether there exists a possible correlation
      between genetic variations in ACAT-1 genes and coronary artery disease (CAD)
      risk. Four polymorphisms (rs1044925, rs11545566, rs12121758 and rs10913733) were
      finally selected and genotyped in 750 CAD patients and 580 health controls, using
      the improved multiplex ligation detection reaction (iMLDR) method. We found that
      the rs11545566 G allele was associated with a significantly elevated CAD risk [GG
      vs. AA: adjusted odds ratio (AOR) = 1.62, 95% confidence interval (CI) = 1.13
      2.32, P = 0.008; GA/GG vs. AA: AOR = 1.67, 95% CI = 1.22-2.29, P = 0.001]. The
      rs10913733 G allele was also associated with a significantly elevated CAD risk
      (GG vs. TT: AOR = 1.57, 95% CI = 1.08-2.28, P = 0.018; GT/GG vs. TT: AOR = 1.39,
      95% CI = 1.07-1.79, P = 0.013). Multivariate linear regression analysis showed
      that the rs11545566 polymorphism was independently associated with the Gensini
      scores (P = 0.005). The Gensini score of subjects in the variant GG genotype
      group and the GG/GA genotype group were higher than the score of subjects in the
      AA genotype group (32.49 +/- 26.60 and 31.26 +/- 26.96 vs. 23.45 +/- 21.64; P =
      0.001 and 0.002, respectively). Our results demonstrate that ACAT-1 rs1154556 and
      rs10913733 polymorphism are novel genetic factors in the development of CAD.
      Rs11545566 was also associated with the severity of CAD.

PMID- 29179499
TI  - Association between IL4, IL6 gene polymorphism and lumbar disc degeneration in
      Chinese population.
AB  - Lumbar disc disease (LDD) is a common musculoskeletal disorder, caused by
      degeneration of intervertebral discs of the lumbar spine and is one of the most
      common musculoskeletal disorders affliction in adult. There is growing evidence
      that LDD has strong genetic determinants. We analyze whether the IL4 and IL6 gene
      polymorphism is related to LDD in Chinese Han population. The participants were
      498 with LDD and 463 without LDD. IL4 and IL6 gene polymorphism were determined
      by Sequenom MassARRAY. We found that SNPs rs1800796(OR = 1.29, 95% CI, 1.07 -
      1.57, p = 0.009), rs1524107(OR = 1.28, 95% CI, 1.05 - 1.55, p = 0.013), rs2069840
      (OR = 1.39, 95% CI, 1.03 - 1.89, p = 0.033) in IL6 gene were significantly
      associated with LDD risk at a 5% level. In addition, genetic models found IL4
      gene (rs2243250) were associated with LDD. In this study, we analyzed and
      associated SNPs of IL4 and IL6 with LDD risk. In summary, four variations
      (rs1800796, rs1524107, rs2069840, rs2243250) of the selected candidate SNPs were
      associated with susceptibility to LDD in our study. The results of this study
      have the guiding significance in clinical work in the future in the treatment of
      lumbar disc herniation patients, not one-sided that the symptoms of low back pain
      only from mechanical oppression.

PMID- 29179500
TI  - hYSK1 promotes cancer cell proliferation and migration through negative
      regulation of p16INK4a under hypoxic conditions.
AB  - The alteration of expression of p16INK4a, a well-known cyclin-dependent kinase
      inhibitor involved in cell cycle control, in tumors is unclear, especially under
      hypoxic conditions. To evaluate p16INK4a regulation, we performed a protein
      microarray analysis. Among 1,800 proteins in the array, we identified hYSK1 as a
      novel protein that interacts with the tumor suppressor p16INK4a. hYSK1, a member
      of the Ste20 family of serine/threonine protein kinases, promotes cell migration
      and tumorigenesis and is activated by oxidative stress. However, the molecular
      mechanisms underlying the oncogenic potential of hYSK1 remain elusive. Here, we
      report that hYSK1 interacts with p16INK4a under hypoxic conditions in tumors,
      where it negatively regulates p16INK4a, enhancing cancer cell migration. Hypoxic
      stimulation of hYSK1 reduces p16INK4a accumulation through p16 promoter
      regulation to interact with unphosporylated SP-1 and increases matrix
      metalloproteinase-2 (MMP-2) expression by activating the MMP-2 promoter
      associated with cell migration and proliferation.Conversely, knocking down hYSK1
      expression activated p16INK4a expression and suppressed MMP-2 expression. Thus,
      hYSK1 is necessary as a trigger for inactivating p16INK4a and activating MMP-2
      during tumor migration, suggesting that hYSK1 is a specific negative regulator of
      the tumor suppressor p16INK4a and may represent a novel molecular target for
      reactivation of tumor suppressor genes in humans.

PMID- 29179501
TI  - The heterogeneous CTV-PTV margins should be given for different parts of tumors
      during tomotherapy.
AB  - Objective: The purpose of this study was to evaluate CTV-PTV margins of tumors
      for tomotherapy. Methods: Setup errors were analyzed for 151 patients receiving
      helical tomotherapy treatment. 53 patients had head and neck tumors, 45 had
      thoracic tumors, 20 had abdominal tumors, and 33 had pelvic tumors. The setup
      errors were calculated in six directions, i.e. +X (left), -X (right), +Y (head), 
      Y (foot), +Z (ventral), and -Z (dorsal), after Megavoltage CT (MVCT) images were
      registered to simulation CT images. And then the CTV-PTV margins were calculated.
      Results: The setup errors along the +Z direction were significantly higher than
      that along the -Z direction (p<0.05). The CTV-PTV margins on +X, -X, +Y, -Y, +Z,
      and -Z directions were asymmetric for all tumors, and the heterogeneity were more
      remarkable on the +Z and -Z directions. The CTV-PTV margins on +Z and -Z were 4.1
      mm, 4.6 mm, 5.2 mm, and 8.4 mm; and 3.9 mm, 7.7 mm, 3.3 mm, and 7.7 mm for head
      and neck tumors, thoracic tumors, abdominal tumors, and pelvic tumors,
      respectively. Conclusions: The CTV-PTV margins for patients with different types
      of tumors were heterogeneous during tomotherapy. The individual margins of six
      directions should be given for those patients who accept tomotherapy.

PMID- 29179502
TI  - What is the optimal radiation dose for non-operable esophageal cancer? Dissecting
      the evidence in a meta-analysis.
AB  - The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized
      inoperable esophageal cancer as supported by INT-0123 trail is now being
      challenged since a radiation dose above 50 Gy has been successfully administered
      with an observable dose-response relationship and insignificant untoward effects.
      Therefore, to ascertain the treatment benefits of different radiation doses, we
      performed a meta-analysis with 18 relative publications. According to our
      findings, a dose between 50 and 70 Gy appears optimal and patients who received
      >= 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P =
      0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75,
      P = 0.003). However, contradictory results of treatment benefit for >= 60 Gy were
      observed in two studies from Western countries, and the pooled treatment benefit
      of >= 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a
      marginal benefit in locoregional control in those treated with high dose (>
      50.4/51 Gy) radiation when compared with those treated with low dose (<= 50.4/51
      Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received >= 60 Gy
      radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant
      metastasis control, neither the > 50.4 Gy nor the >= 60 Gy treated group had any
      treatment benefit as compared to the groups that received <= 50.4 Gy and < 60 Gy
      group respectively. Taken together, a dose range of 50 to 70 Gy radiation with
      CCRT is recommended for non-operable EC patients. A dose of >= 60 Gy appears to
      be better in improving overall survival and locoregional control, especially in
      Asian countries, while the benefit of >= 60 Gy radiation in Western countries
      still remains controversial.

PMID- 29179503
TI  - Can polysaccharide K improve therapeutic efficacy and safety in gastrointestinal
      cancer? a systematic review and network meta-analysis.
AB  - Objective: To assess the comparative efficacy and safety of polysaccharide K
      (PSK), with or without chemotherapy, for patients with gastrointestinal cancer
      (GIC) through a systematic review and network meta-analysis. Materials and
      Methods: We performed a network meta-analysis to identify evidence from
      randomized controlled trials. We searched PubMed, Embase and the Cochrane Library
      for publications up to May 2017. The prespecified primary efficacy outcomes were
      1-7 year overall survival (OS), while the secondary efficacy outcomes were 1-7
      year disease-free survival (DFS); we performed subgroup analyses and meta
      regressions according to the cancer type (colorectal, esophagus and gastric
      cancer) and treatment arms (with or without chemotherapy). Safety outcomes were
      side effects of PSK. We conducted pairwise meta-analyses using a random-effects
      model and then performed random-effects network meta-analyses. Results: A total
      of 23 trials were eligible, involving 10684 patients and 13 intervention arms.
      PSK treatment significantly increased 1-5 year OS and resulted in positive trends
      in 6-7 year OS; significant increases were also found in 1-7 year DFS, while no
      increase in side effects was observed. Significant efficacy outcomes obvious in
      colorectal and gastric cancer groups, as well as PSK combined with chemotherapy
      groups (iv, po, iv+po). Network meta-analysis revealed that PSK combined with
      chemotherapy was superior, with significantly increased 3-year and 5-year OS. The
      study is registered with PROSPERO (CRD42017065193). Conclusions: The adjuvant
      immunochemotherapy agent PSK is effective and safe for patients with GIC. PSK
      combined with chemotherapy appears to be the preferred application of PSK.

PMID- 29179504
TI  - Risk factors associated with fatality of severe fever with thrombocytopenia
      syndrome: a meta-analysis.
AB  - Severe fever with thrombocytopenia syndrome is an emerging life-threatening
      infectious disease identified in 2009. Given high case-fatality rate among
      patients with severe fever with thrombocytopenia syndrome, identification of the
      risk factors at acute phase associated with fatality is crucial for treatment.
      Therefore, we aimed to meta-analytically evaluate risk factors of fatal clinical
      outcome of severe fever with thrombocytopenia syndrome. 238 fatal cases and 873
      non-fatal cases from 12 studies were included in this meta-analysis. Elder age
      and high viral load were significantly associated with fatal clinical outcome.
      Further, severe fever with thrombocytopenia syndrome patients with fatal clinical
      outcome had significantly reduced level of albumin and platelet count, higher
      level of serum alanine aminotransferase, aspirate aminotransferase, lactic acid
      dehydrogenase and creatinine phosphokinase, and prolonged activated partial
      thromboplastin time, comparing with mild patients. These disturbed parameters
      function as predictors to warn fatal clinical outcome of the disease. Moreover,
      ribavirin has a minimal impact to alleviate disease progression of severe fever
      with thrombocytopenia syndrome. In conclusion, our finding demonstrates a panel
      of factors associated with fatality of SFTS disease, which have important
      implications during clinical practice.

PMID- 29179506
TI  - The diagnostic and prognostic value of CHFR hypermethylation in colorectal
      cancer, a meta-analysis and literature review.
AB  - The Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a
      mitotic checkpoint and tumor-suppressor gene, its loss contributes tumorigenesis
      of epithelial cancers including colorectal carcinoma (CRC). The diagnostic and
      prognostic value of CHFR promoter hypermethylation in CRC remains unclear. This
      study aimed to conduct a meta-analysis and literature review and investigate
      clinicopathological significance of CHFR promoter hypermethylation in CRC. The
      following online database were used: PubMed, EMBASE, and Web of Science up to
      March 2017. Odds Ratios (OR) and Hazard Ratios (HR) with 95% corresponding
      confidence intervals (CIs) were calculated. A total of seven relevant articles
      were available for meta-analysis which included 966 patients. The frequency of
      CHFR promoter hypermethylation significantly increased in CRC compared to normal
      colorectal mucosa tissue, pooled OR was 8.35, p < 0.00001. CHFR promoter
      hypermethylation was not significantly correlated to stage, OR was 1.16, p =
      0.63. However, CHFR promoter hypermethylation was more frequently observed in CRC
      with positive lymph nodes metastasis than CRC with negative lymph nodes
      metastasis, OR was 0.46, p = 0.03. Additionally CHFR promoter hypermethylation
      was significantly related to poor overall survival in patients with CRC, HR was
      0.62, p = 0.008. Based on these results, tumor CHFR promoter hypermethylation is
      not only a diagnostic biomarker for CRC, but also a prognostic marker. CHFR
      promoter hypermethylation is significantly associated with worse overall survival
      in patients with CRC. Our data suggested that CHFR could be a potential drug
      target for development of demethylation treatment for patients with CRC.

PMID- 29179505
TI  - MicroRNA-181 as a prognostic biomarker for survival in acute myeloid leukemia: a
      meta-analysis.
AB  - Accumulating evidence has indicated that microRNA-181 (miR-181) is dysregulated
      in hematological malignancies, and associates with the clinical outcomes.
      However, the association of miR-181 expression levels with acute myeloid leukemia
      (AML) remains inconclusive, as publications from different groups have reported
      contradictory results. In this manuscript, a meta-analysis was performed to
      assess the prognostic significance of miR-181 in AML patients. Eligible studies
      were retrieved from PubMed, Embase and Cochrane Library databases, and a total of
      6 studies including 815 AML patients were included in the final analysis. Hazard
      ratios (HRs) and their corresponding 95% confidence intervals (CIs) were
      extracted and pooled to investigate the correlation between miR-181 and the
      survival of AML patients. Our results showed that elevated miR-181 expression was
      associated with increased survival in 395 American patients, and reduced survival
      in 325 Chinese patients. Both subgroup analyses and meta-regression indicated
      that the origin of AML patients contributed to the heterogeneity in the datasets
      evaluating the correlation between overall survival (OS) and miR-181. These
      results indicate that miR-181 can be used as a promising prognostic biomarker in
      AML patients, which may depend on the origin of patient population.

PMID- 29179507
TI  - Meta-analysis of the clinical value of abnormally expressed long non-coding RNAs
      for pancreatic cancer.
AB  - Pancreatic cancer (PC) is one of the most lethal malignant neoplasms of the
      digestive system. Long non-coding RNAs (lncRNAs) are a novel type of non-protein
      coding transcripts that play an important role in pancreatic carcinogenesis. We
      herein aimed to meta-analyze the diagnostic and prognostic significance of lncRNA
      expression profiles in PC. A comprehensive retrieval of eligible studies was
      performed based on the online databases. Quantitative meta-analyses of the pooled
      diagnostic parameters and hazard ratios (HRs) were enabled by using standard
      statistical methods. A total of 16 studies comprising 1386 PC patients were
      included. The pooled effect sizes exhibited that lncRNA expression profile
      achieved a combined sensitivity of 0.82 (95% CI: 0.72-0.89), specificity of 0.77
      (95% CI: 0.65-0.86) and AUC (area under curve) of 0.87 (95% CI: 0.83-0.89) in
      distinguishing patients with PC from noncancerous controls. Notably, abnormally
      expressed lncRNAs were markedly associated with unfavorable overall survival (OS)
      in PC (univariate analysis: HR = 1.52, 95% CI: 1.04-2.22, P = 0.031; multivariate
      analysis: HR = 1.55, 95% CI: 1.19-2.02, P = 0.001). Statistical significance was
      also observed in our stratified analyses grouped by clinicopathologic features.
      In conclusion, abnormal lncRNA expression profiles could be rated as promising
      biomarker(s) to enable diagnosis and predict the prognosis of PC.

PMID- 29179508
TI  - Homeobox protein CDX2 as a prognostic biomarker in solid malignancies: a meta
      analysis.
AB  - Background: CDX2 is a caudal-homeobox gene and its expression is abnormal in
      numerous tumour cell types. Nevertheless, its prognostic value for solid tumours
      requires further investigation. Hence, we conducted a meta-analysis to determine
      the significance of CDX2 as a prognostic biomarker in solid malignancies
      systematically. Materials and Methods: We performed a systematic literature
      search in PUBMED and EMBASE up to May 2017. Retrospective studies comparing the
      prognostic value of different CDX2 levels in human malignancies were included.
      Data extractions and methodological assessments were performed separately by two
      investigators using a standard procedure. The statistical procedures were
      performed using Review Manager 5.3 and STATA/MP 14.0. Results: A total of 26
      retrospective studies met the inclusion criteria and comprised 5008 participants.
      Patients with CDX2 overexpression had significantly better 3-year, 5-year, 10
      year and disease-free survival outcomes in solid malignancies, regardless of the
      cancer type, mean age, and source region. Nevertheless, there was no significant
      difference in the patients from Europe. The expression level of CDX2 was not
      statistically associated with cancer relapse. Moreover, our analysis showed that
      CDX2 overexpression is correlated to better responses to chemotherapy in patients
      with TNM IV stage cancers. The stability of the pooled outcomes was verified by
      sensitivity analysis. The funnel plots, Egger's test and Begg's test jointly
      confirmed that there was no publication bias. Conclusions: Overexpression of CDX2
      is a reliable biomarker of a better prognosis in solid malignancies.

PMID- 29179509
TI  - Benign and malignant breast lesions identification through the values derived
      from shear wave elastography: evidence for the meta-analysis.
AB  - Objective: The analysis was aimed to evaluate the diagnostic accuracy of shear
      wave elastography (SWE) for malignant breast lesions through a meta-analysis.
      Materials and Methods: Related articles were searched in databases of Pubmed,
      Embase and Cochrane library. Overall sensitivity and specificity were analyzed
      with DerSimonian and Laird random effects model. Area under curve (AUC) with
      corresponding 95% confidence interval were also analyzed to evaluate the
      diagnostic accuracy of SWE. P value < 0.05 predicted the significant
      heterogeneity between study. Sensitivity and publication bias were assessed as
      well. Results: According to the inclusion criteria, 25 articles were selected. 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, while 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 (VTTQ) 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 receiver
      operating curve (sROC) than that of 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). Conclusions: SWE serves as an accurate diagnostic
      technology for discriminating malignant and benign breast lesions.

PMID- 29179510
TI  - Targeting epigenetics for treatment of BRAF mutated metastatic melanoma with
      decitabine in combination with vemurafenib: A phase lb study.
AB  - Introduction: Epigenetic modifications play an important role in progression and
      development of resistance in V600EBRAF positive metastatic melanoma. Therefore,
      we hypothesized that the action of vemurafenib (BRAF inhibitor) can be made more
      effective by combining with low dose decitabine (a DNA methyltransferase
      inhibitor). The primary objective of this phase lb study was to determine the
      dose limiting toxicity and maximum tolerated dose of combination of subcutaneous
      decitabine with oral vemurafenib in patients with V600EBRAF positive metastatic
      melanoma with or without any prior treatment. Experimental Design: The study
      employed 3+3 dose escalation combining subcutaneous decitabine at different doses
      and schedules (4 cohorts) with the standard oral dose of vemurafenib 960 mg twice
      daily. Preclinical assessment and further analysis were also performed in A375
      melanoma cell line. Results: Fourteen patients received study treatment. No dose
      limiting toxicity was encountered and maximum tolerated dose was not reached.
      Important toxicities included fatigue, increased creatinine, neutropenia,
      leucopenia, hypophosphatemia, rash and hyperuricemia. Three patients achieved
      complete response, three had partial response and five had stable disease.
      Preclinical assessment demonstrated action of the combination which delayed the
      development of acquired resistance and improved duration of treatment
      sensitivity. Conclusions: The combination of oral vemurafenib with subcutaneous
      decitabine is safe and showed activity in V600EBRAF positive metastatic melanoma.
      Since most responses were seen in cohort 1, which utilized low-dose, long-term
      decitabine, future studies of this combination treatment should utilize longer
      duration of decitabine, at the lowest dose of 0.1 mg/kg.

PMID- 29179511
TI  - The role of endobronchial ultrasound elastography in the diagnosis of mediastinal
      and hilar lymph nodes.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has
      been widely used for diagnosis and mediastinal lymph nodes staging in patients
      with suspicious lung cancer. Ultrasound elastography is a novel sonographical
      technique that can evaluate tissue compressibility. The aim of the present study
      was to investigate the diagnostic yield of elastography for differentiating
      malignant and benign mediastinal lymph nodes. Conventional EBUS B-mode features,
      including size, shape, border distinction, echogenicity, central hilar structure
      with central blood vessel and coagulation necrosis were also evaluated. The
      ultrasonic features were compared with the pathological results from EBUS-TBNA.
      133 lymph nodes in 60 patients were assessed. Elastography displayed the highest
      area under the curve (AUC) (type 3 versus type 1: AUC, 0.825; 95% confidence
      interval [CI], 0.707-0.910) with an impressive sensitivity (100%) and an
      acceptable specificity (65%). The combined model covering the four positive
      criteria (elastography, heterogeneity, size, and shape) showed that the odds
      ratio for malignance is 9.44 with a 95% CI of 3.99 to 22.32 (p <0.0001). The
      combined model was superior to elastography alone (AUC, 0.851; sensitivity,
      89.89%; specificity, 72.73%; p <0.0001). This prospective study showed that
      elastography is a feasible technique for classifying mediastinal lymph nodes,
      especially in combination with conventional EBUS imaging.

PMID- 29179512
TI  - Time to local recurrence as a predictor of survival in unrecetable gastric cancer
      patients after radical gastrectomy.
AB  - Local recurrence is common after radical surgery. However, the factors that
      contribute to survival after local recurrence remain unclear. In this
      retrospective study we analyzed the relationship between time to recurrence and
      survival after recurrence in 74 patients with locally recurrent gastric cancer.
      All patients received palliative radiotherapy with or without chemotherapy. The
      patients were divided into two groups according to the time between gastrectomy
      and local recurrence: early local recurrence (ELR, < 12 months after primary
      surgery), and late local recurrence (LLR, >=12 months after primary surgery). The
      median overall survival (OS) time was 15 months for patients with ELR and 25
      months for LLR patients. Univariate and multivariate analysis revealed that time
      to local recurrence was significantly associated with OS after local recurrence
      (P = 0.001). The hazard ratio of ELR compared with LLR patients was 0.442 (95%
      confidence interval: 0.264-0.741). These results indicate that early local
      recurrence predicted poor prognosis in gastric cancer patients with unresectable
      local recurrence.

PMID- 29179514
TI  - Impact of preoperative diagnostic TURBT on progression-free survival in patients
      with pathological high-grade, stage T3/T4 bladder urothelial carcinoma.
AB  - Transurethral bladder tumor resection (TURBT) reportedly increases the
      circulating tumor cell count in patients with urothelial carcinoma of the bladder
      (UCB). To determine whether diagnostic TURBT leads to poorer progression-free
      survival (PFS) than diagnostic cystoscopic biopsy, we retrospectively reviewed
      the records of 96 consecutive primary pathological high-grade, stage T3/T4 UCB
      patients treated with radical cystectomy (RC) between January 2009 to December
      2013. Clinicopathological features were collected from the medical records. PFS
      was determined from Kaplan-Meier curves, and potential independent prognostic
      factors for PFS were identified based on multivariable Cox analysis. During the
      follow-up period (median, 29 months), 43 patients experienced tumor progression
      (40 received diagnostic TURBT, 56 received cystoscopic biopsy). Patients who
      received cystoscopic biopsy had better PFS than those who received diagnostic
      TURBT (p = 0.008). Additionally, diagnostic TURBT was a significant risk factor
      for tumor metastasis in both univariable (HR: 2.219; 95% CI: 1.207-4.079; p =
      0.010) and multivariable (HR: 2.455; 95% CI: 1.278-4.714; p = 0.007) Cox
      analyses. The present study provides the first evidence that diagnostic TURBT
      before RC negatively affects PFS in patients with pathological high-grade, stage
      T3/T4 UCB.

PMID- 29179513
TI  - The impacts of surgery of the primary cancer and radiotherapy on the survival of
      patients with metastatic rectal cancer.
AB  - The role of surgery of the primary cancer and radiation in metastatic colorectal
      cancer (mCRC) is still controversial currently, and evidence implied that colon
      cancer (CC) and rectal cancer (RC) should be treated with difference. Hence we
      focused on metastatic rectal cancer (mRC) solely to compare the cancer cause
      specific survival (CSS) of patients receiving varied treatments of the primary
      cancer: no treatment, surgery only, radiation only, and surgery plus radiation,
      based on the records of the Surveillance, Epidemiology, and End Results (SEER)
      database. A total of 8669 patients were included. Results demonstrated that the 2
      year CSS was 28.1% for no treatment group, 30.7% for only radiation group, 50.2%
      for only surgery group, and 66.5% for surgery plus radiation group, reaching
      statistical difference (P < 0.001). Furthermore, the CSSs of mRC patients in the
      surgery group were similar regardless of resection ranges (P = 0.44). Besides, we
      analyzed the prognostic factors for mRC and found carcinoembryonic antigen (CEA)
      level, metastasis (M) stage, Tumor (T) stage, tumor size, differentiate grade,
      age and marital status should be taken into consideration when estimating the
      prognosis. Particularly, patients with normal CEA level or M1a stage showed a
      significant survival advantage. Overall, present study suggested that surgery of
      the primary cancer and radiation might help to improve the survival of mRC
      patients, especially when both treatments were conducted. Our results may assist
      clinicians to make better treatment strategy for patients with mRC.

PMID- 29179515
TI  - Characteristics, survival, and risk factors of Chinese young lung cancer
      patients: the experience from two institutions.
AB  - Limited data is available regarding lung cancer in Chinese young adults. This
      study was aimed to determine the characteristics, survival, and prognostic
      factors of young lung cancer patients in China. We reviewed demographic and
      clinical data, and survival information of 420 young patients (20-45 years old)
      diagnosed with lung cancer in two Chinese hospitals between 2000 and 2013. The
      results showed that lung cancer occurred more frequently (70%) and affected more
      males than females (43.8% vs 26.7%) in patients older than 36; whereas, more
      females were affected under age 35 (16.7% vs 12.8%). Most patients had
      adenocarcinoma (67.6%) and stage IV disease (72.4%) at presentation. The median
      survival of all young patients with lung cancer was 44 months (95% CI: 39-49), of
      which patients with stage I-IIIA disease had a longer survival than those with
      stage IIIB/IV disease (101 vs 22 months, p < 0.001). No significant difference in
      survival was found in patients having different histological subtypes or genders.
      Multivariate analysis revealed that high exposure risk occupations, smoking,
      family history of lung cancer were risk factors of young lung cancer patients.
      This study provides an overview of the clinical characteristics, patterns and
      prognostic factors of young patients with lung cancer in China.

PMID- 29179516
TI  - Lymph node ratio, but not the total number of examined lymph nodes or lymph node
      metastasis, is a predictor of overall survival for pancreatic neuroendocrine
      neoplasms after surgical resection.
AB  - Aim: To evaluate the prognostic significance of lymph node metastasis, extent of
      examined lymph nodes (ELNs) and lymph node ratio (LNR) for resected pancreatic
      neuroendocrine neoplasms (pNENs). Materials and Methods: Surgically resected
      pNENs were assimilated from the Surveillance, Epidemiology, and End Results
      database. Kaplan-Meier and Cox proportional hazard models were used to examine
      the prognostic effect of clinicopathological characteristics on overall survival;
      Harrell's concordance index was performed to assess the prognostic accuracy of
      all independent prognostic factors; and the Spearman's rank correlation was used
      to assess the correlation between LNR and other clinicopathological
      characteristics. Results: Totally, 1,273 pathologically confirmed pNENs were
      included in our study. The extent of ELNs failed to show any survival benefit in
      entire cohort (ELNs <= 12 vs. ELNs > 12, P = 0.072) or pNENs without lymph node
      metastasis (ELNs <= 28 vs. ELNs > 28, P = 0.108). Lymph node metastasis and LNR >
      0.40 were significantly (both P < 0.001) adverse prognostic factors of overall
      survival. However, only LNR > 0.40 was the independent predictor of survival
      after adjusted for other clinicopathological characteristics. Besides LNR, the
      age, gender, primary tumor site, grade and stage also were the independent
      predictors of overall survival; and this survival model had an acceptable
      predictive power (Harrell's concordance index, 0.731). Conclusions: The current
      study suggested that the LNR, not the total number of ELNs and the lymph node
      metastasis, is an independent prognostic indicator of overall survival for pNENs
      after surgical resection.

PMID- 29179517
TI  - A phase I trial of NK-92 cells for refractory hematological malignancies
      relapsing after autologous hematopoietic cell transplantation shows safety and
      evidence of efficacy.
AB  - Background: Autologous NK cell therapy can treat a variety of malignancies, but
      is limited by patient-specific variations in potency and cell number expansion.
      In contrast, allogeneic NK cell lines can overcome many of these limitations.
      Cells from the permanent NK-92 line are constitutively activated, lack inhibitory
      receptors and appear to be safe based on two prior phase I trials. Materials and
      Methods: We conducted a single-center, non-randomized, non-blinded, open-label,
      Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory
      hematological malignancies who relapsed after autologous hematopoietic cell
      transplantation (AHCT). The objectives were to determine safety, feasibility and
      evidence of activity. Patients were treated at one of three dose levels (1 * 109
      cells/m2, 3 * 109 cells/m2 and 5 * 109 cells/m2), given on day 1, 3 and 5 for a
      planned total of six monthly cycles. Results: Twelve patients with lymphoma or
      multiple myeloma who relapsed after AHCT for relapsed/refractory disease were
      enrolled in this trial. The treatment was well tolerated, with minor toxicities
      restricted to acute infusional events, including fever, chills, nausea and
      fatigue. Two patients achieved a complete response (Hodgkin lymphoma and multiple
      myeloma), two patients had minor responses and one had clinical improvement on
      the trial. Conclusions: Irradiated NK-92 cells can be administered at very high
      doses with minimal toxicity in patients with refractory blood cancers, who had
      relapsed after AHCT. We conclude that high dose NK-92 therapy is safe, shows some
      evidence of efficacy in patients with refractory blood cancers and warrants
      further clinical investigation.

PMID- 29179518
TI  - Reassessment of different criteria for diagnosing post-hepatectomy liver failure:
      a single-center study of 1683 hepatectomy.
AB  - Assessing the incidence and severity of post-hepatectomy liver failure (PHLF) can
      be based on different criteria, and we wished to compare the diagnostic
      efficiency and specificity of different PHLF criteria. Data from patients
      (n=1683) who received hepatectomies in the liver surgery department of Peking
      Union Medical College Hospital from April 2008 to August 2014 were
      retrospectively analyzed. Possible PHLF patients were screened according to the
      criteria of the International Study Group of Liver Surgery (ISGLS). Subsequently,
      other PHLF evaluation methods, including Child-Pugh score, "50-50" criteria,
      Model for End-Stage Liver Disease (MELD) score, and Clavien-Dindo classification
      were used to assess the suspected PHLF patients, and statistical analysis was
      performed for correlation of these methods with clinical prognoses. Using ISGLS
      grading, 40 cases (2.38%) were suspected to have PHLF, among whom 5 (0.30%)
      patients died. Of the 40 cases there were 9 patients of ISGLS grade A, 21 of
      grade B, and 10 of grade C. Among the entire group, Child-Pugh scoring showed 3
      patients in grade A, 35 in grade B, and 2 in grade C, while only 5 patients met
      the "50-50" criteria. Interestingly, MELD scores >=11 points were found only in 3
      cases. Twenty-eight patients were classified as Clavien-Dindo grade I, 8 as grade
      II, 3 as grade III, and 1 as grade IV. Prothrombin time on postoperative day 5
      (PT5), ISGLS, and Clavien-Dindo were found to have significant correlation with
      the prognosis of PHLF (r>0.5, p <0.05), thus can be used as prognosis predictors
      for PHLF patients.

PMID- 29179519
TI  - Sleep in lonely heroin-dependent patients receiving methadone maintenance
      treatment: longer sleep latency, shorter sleep duration, lower sleep efficiency,
      and poorer sleep quality.
AB  - Given the socially isolated status of Chinese heroin-dependent patients (HDPs)
      and the significant association between loneliness and sleep problem in the
      general population, the impact of loneliness on sleep of HDPs is potentially
      substantial. The study aimed to test whether loneliness is associated with poor
      sleep in terms of quantity and quality in a consecutive sample of Chinese HDPs
      receiving methadone maintenance treatment (MMT). The study participants were 603
      HDPs of three MMT clinics in Wuhan, China. Data on socio-demographic and clinical
      characteristics were collected by a standardized self-administered questionnaire.
      Sleep outcomes included sleep latency, sleep duration, sleep efficiency, and
      sleep quality. We measured depressive symptoms, loneliness, and sleep quality by
      using Zung's Self-rating Depression Scale, the single-item self-report of
      loneliness, and the Pittsburgh Sleep Quality Index, respectively. Multiple linear
      regression was used to examine whether loneliness is independently associated
      with sleep measures. After controlling for the confounding effects of potential
      socio-demographic and clinical variables, loneliness was significantly associated
      with longer sleep latency, shorter sleep duration, lower sleep efficiency, and
      poorer sleep quality. Loneliness may exacerbate sleep disturbance in Chinese HDPs
      of MMT clinics. Psychosocial interventions aimed at reducing loneliness in MMT
      clinics would improve the sleep of HDPs.

PMID- 29179521
TI  - Silibinin: an old drug for hematological disorders.
AB  - Introduction: Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is
      the principal and the most biologically active component of silymarin. It is
      efficient in the treatment of acute and chronic liver disorders caused by toxins,
      drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous
      studies, we explored the anti-cancer efficacy in common cancers, such as lung,
      prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma.
      Interestingly, silibinin is still not solely limited to the treatment of these
      diseases. Recent research endeavors suggest that silibinin may function diversely
      and serve as a novel therapy for hematological disorders. Areas covered: It
      discovered several interesting viewpoints in the widely studied mechanisms of
      silibinin in the hematological disorders. Expert commentary: In this report, we
      review the up-to-date findings of more potency roles of silibinin in beta
      thalassemia (beta-TM), acute myeloid leukemia (AML), anaplastic large cell
      lymphoma (ALCL) and multiple myelomas (MM) therapy and attempt to clarify the
      mechanisms underlying its effects. There are two viewpoints: First, The
      functional mechanisms of silibinin in AML cells via regulating cell
      differentiation to exert anti-cancer effect; Second, combination treatment
      strategy may be a good choice.

PMID- 29179520
TI  - A comprehensive review of heregulins, HER3, and HER4 as potential therapeutic
      targets in cancer.
AB  - Heregulins (HRGs) bind to the receptors HER3 or HER4, induce receptor
      dimerization, and trigger downstream signaling that leads to tumor progression
      and resistance to targeted therapies. Increased expression of HRGs has been
      associated with worse clinical prognosis; therefore, attempts to block HRG
      dependent tumor growth have been pursued. This manuscript summarizes the function
      and signaling of HRGs and review the preclinical evidence of its involvement in
      carcinogenesis, prognosis, and treatment resistance in several malignancies such
      as colorectal cancer, non-small cell lung cancer, ovarian cancer, and breast
      cancer. Agents in preclinical development and clinical trials of novel
      therapeutics targeting HRG-dependent signaling are also discussed, including anti
      HER3 and -HER4 antibodies, anti-metalloproteinase agents, and HRG fusion
      proteins. Although several trials have indicated an acceptable safety profile,
      translating preclinical findings into clinical practice remains a challenge in
      this field, possibly due to the complexity of downstream signaling and patterns
      of HRG, HER3 and HER4 expression in different cancer subtypes. Improving patient
      selection through biomarkers and understanding the resistance mechanisms may
      translate into significant clinical benefits in the near future.

PMID- 29179522
TI  - Acetylation and deacetylation in cancer stem-like cells.
AB  - Cancer stem-like cell (CSC) model has been established to investigate the
      underlying mechanisms of tumor initiation and progression. The imbalance between
      acetylation and deacetylation of histone or non-histone proteins, one of the
      important epigenetic modification processes, is closely associated with a wide
      variety of diseases including cancer. Acetylation and deacetylation are involved
      in various stemness-related signal pathways and drive the regulation of self
      renewal and differentiation in normal developmental processes. Therefore, it is
      critical to explore their role in the maintenance of cancer stem-like cell
      traits. Here, we will review the extensive dysregulations of acetylation found in
      cancers and summarize their functional roles in sustaining CSC-like properties.
      Additionally, the use of deacetyltransferase inhibitors as an effective
      therapeutic strategy against CSCs is also discussed.

PMID- 29179525
TI  - Aliskiren therapy in hypertension and cardiovascular disease: a systematic review
      and a meta-analysis.
AB  - The efficacy and safety of aliskiren combination therapy with angiotensin
      converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in
      patients with hypertension and cardiovascular disease remains attractive
      attention. We searched the Cochrane Central Register, the Clinical Trials
      Registry, EMBASE, MEDLINE and PubMed for relevant literatures up to January 2017.
      A total of 13 randomized controlled trials (RCTs) with 12222 patients were
      included in this study, and the combined results indicated that aliskiren in
      combination therapy with ACEIs or ARBs had remarkable effects in reducing
      systolic blood pressure (SBP) [weighted mean differences (WMD), -4.20; 95%
      confidential intervals (CI) -5.44 to -2.97; I2 , 29.7%] and diastolic blood
      pressure (DBP: WMD, -2.09; 95% CI -2.90 to -1.27; I2 , 0%) when compared with
      ACEIs or ARBs monotherapy, but with significantly increased the risk of
      hyperkalaemia [relative risk (RR), 1.45; 95% CI 1.28 to 1.64; I2 ,10.6 %] and
      kidney injury ( RR, 1.92; 95% CI 1.14 to 3.21; I2 , 0%). Besides, there was no
      significant difference in the incidence of major cardiovascular events (RR, 0.95;
      95% CI 0.89 to 1.02; I2 , 0%) between the combined therapy and ACEIs or ARBs
      monotherapy. In conclusion, this meta-analysis demonstrated that aliskiren in
      combination therapy with ACEs/ARBs could control BP effectively, but is
      associated with increasing risks of hyperkalaemia and kidney injury, and have no
      benefit in preventing of major cardiovascular events.

PMID- 29179523
TI  - Management of intracranial melanomas in the era of precision medicine.
AB  - Melanoma is the most lethal of skin cancers, in part because of its proclivity
      for rapid and distant metastasis. It is also potentially the most neurotropic
      cancer in terms of probability of CNS metastasis from the primary lesion. Despite
      surgical resection and radiotherapy, prognosis remains guarded for patients with
      brain metastases. Over the past five years, a new domain of personalized therapy
      has emerged for advanced melanoma patients with the introduction of BRAF and
      other MAP kinase pathway inhibitors, immunotherapy, and combinatory therapeutic
      strategies. By targeting critical cellular signaling pathways and unleashing the
      adaptive immune response against tumor antigens, a subset of melanoma patients
      have demonstrated remarkable responses to these treatments. Over time, acquired
      resistance to these modalities inexorably develops, providing new challenges to
      overcome. We review the rapidly evolving terrain for intracranial melanoma
      treatment, address likely and potential mechanisms of resistance, as well as
      evaluate promising future therapeutic approaches currently under clinical
      investigation.

PMID- 29179524
TI  - Predictors of hematoma expansion predictors after intracerebral hemorrhage.
AB  - Despite years of effort, intracerebral hemorrhage (ICH) remains the most
      devastating form of stroke with more than 40% 30-day mortality worldwide.
      Hematoma expansion (HE), which occurs in one third of ICH patients, is strongly
      predictive of worse prognosis and potentially preventable if high-risk patients
      were identified in the early phase of ICH. In this review, we summarize data from
      recent studies on HE prediction and classify those potential indicators into four
      categories: clinical (severity of consciousness disturbance; blood pressure;
      blood glucose at and after admission); laboratory (hematologic parameters of
      coagulation, inflammation and microvascular integrity status), radiographic
      (interval time from ICH onset; baseline volume, shape and density of hematoma;
      intraventricular hemorrhage; especially the spot sign and modified spot sign) and
      integrated predictors (9-point or 24-point clinical prediction algorithm and
      PREDICT A/B). We discuss those predictors' underlying pathophysiology in HE and
      present opportunities to develop future therapeutic strategies.

PMID- 29179530
TI  - Lamivudine: fading into the mists of time.

PMID- 29179528
TI  - Ischemic stroke in patients with POEMS syndrome: a case report and comprehensive
      analysis of literature.
AB  - Background: POEMS syndrome is a rare multi-systemic disease characterized by
      polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin
      changes. Arterial or venous thrombosis is a less-common complication of POEMS
      syndrome. Ischemic stroke has also been reported sporadically. However, the
      association between POEMS syndrome and ischemic stroke has not been entirely
      understood. Methods: A case of ischemic stroke caused by cerebral vasculitis in a
      patient with POEMS syndrome was presented. Then a comprehensive review and
      analysis of the literature were performed. Results: A total of 28 patients were
      identified. The common clinical manifestations of POEMS syndrome were rather non
      specific in patients with ischemic stroke compared with those of patients without
      ischemic stroke. Twenty patients were found with multiple ischemic lesions
      (71.5%). In the 25 patients who had undergone the evaluation of cerebral
      arteries, nineteen patients (76.0%) were found with cerebral vasculopathy. Twelve
      patients (48.0%) had more than one cerebral artery involved. Ischemic events were
      documented in 8 patients even when they were undergoing all the therapy for
      ischemic stroke. Ten (55.6%) of the 18 patients who had survival data died within
      two years after stroke events. Conclusion: Comprehensive analysis of literature
      revealed several trends in patients with ischemic stroke and POEMS syndrome
      including a low survival rate and a preponderance of cerebral vasculopathy and
      multiple cerebral arteries affected. Ischemic stroke may be a poor outcome
      predictor in patients with POEMS syndrome. Further researches focusing on a
      larger cohort may help in better characterizing and treating this rare
      complication of POEMS syndrome.

PMID- 29179526
TI  - Calcium influx and sperm-evoked calcium responses during oocyte maturation and
      egg activation.
AB  - Under the guidance and regulation of hormone signaling, large majority of
      mammalian oocytes go through twice cell cycle arrest-resumption prior to the
      fertilized egg splits: oocyte maturation and egg activation. Cytosolic free
      calcium elevations and endoplasmic reticulum calcium store alternations are
      actively involved in triggering the complex machineries and events during
      oogenesis. Among these, calcium influx had been implicated in the replenishment
      of endoplasmic reticulum store during oocyte maturation and calcium oscillation
      during egg activation. This process also drove successful fertilization and early
      embryo development. Store-operated Ca2+ entry, acts as the principal force of
      calcium influx, is composed of STIM1 and Orai1 on the plasma membrane. Besides,
      transient receptor potential channels also participate in the process of calcium
      inwards. In this review, we summarize the recent researches on the spatial
      temporal distribution of store-operated calcium entry components and transient
      receptor potential channels. Questions about how these channels play function for
      calcium influx and what impacts these channels have on oocytes are discussed. At
      the time of sperm-egg fusion, sperm-specific factor(s) diffuse and enable eggs to
      mount intracellular calcium oscillations. In this review, we also focus on the
      basic knowledge and the modes of action of the potential sperm factor
      phospholipase C zeta, as well as the downstream receptor, type 1 inositol 1,4,5
      trisphosphate receptor. From the achievement in the previous several decades, it
      is easy to find that there are too many doubtful points in the field that need
      researchers take into consideration and take action in the future.

PMID- 29179531
TI  - Solvation of Amides in DMSO and CDCl3: An Attempt at Quantitative DFT-Based
      Interpretation of 1H and 13C NMR Chemical Shifts.
AB  - The study concerns N-methyl-2-pyrrolidinone, N,N-dimethylformamide, 2
      pyrrolidinone, N-methylformamide, and formamide in DMSO-d6 and CDCl3 solutions.
      It has been shown that the results of DFT calculations [B3LYP and/or PBE0 6
      311++G(2d,p), PCM] of molecular geometries and magnetic shielding are able to
      reproduce very well the amide 1H NMR and 13C NMR chemical shifts measured in
      these solvents provided that the specific solvation of the solute molecules and
      their association are taken into account and also that comparison of the
      experimental and theoretical data is carefully done. Analysis of the chemical
      shift data points out that in CDCl3 solutions primary and secondary amides are
      partially associated and that their carbonyl oxygen lone electron pairs are
      specifically solvated by solvent molecules. At the same time, association of the
      amides seems to be of minor importance in DMSO, while their N-H hydrogens form
      strong hydrogen bonds with solvent molecules.

PMID- 29179527
TI  - Hitting the nail on the head: combining oncolytic adenovirus-mediated virotherapy
      and immunomodulation for the treatment of glioma.
AB  - Glioblastoma is a highly aggressive malignant brain tumor with a poor prognosis
      and the median survival 14.6 months. Immunomodulatory proteins and oncolytic
      viruses represent two treatment approaches that have recently been developed for
      patients with glioblastoma that could extend patient survival and result in
      better treatment outcomes for patients with this disease. Together, these
      approaches could potentially augment the treatment efficacy and strength of these
      anti-tumor therapies. In addition to oncolytic activities, this combinatory
      approach introduces immunomodulation locally only where cancerous cells are
      present. This thereby results in the change of the tumor microenvironment from
      immune-suppressive to immune-vulnerable via activation of cytotoxic T cells or
      through the removal of glioma cells immune-suppressive capability. This review
      discusses the strengths and weaknesses of adenoviral oncolytic therapy, and
      highlights the genetic modifications that result in more effective and targeted
      viral agents. Additionally, the mechanism of action of immune-activating agents
      is described and the results of previous clinical trials utilizing these
      treatments in other solid tumors are reviewed. The feasibility, synergy, and
      limitations for treatments that combine these two approaches are outlined and
      areas for which more work is needed are considered.

PMID- 29179532
TI  - Induced Superaerophobicity onto a Non-superaerophobic Catalytic Surface for
      Enhanced Hydrogen Evolution Reaction.
AB  - Despite tremendous progress in the development of novel electrocatalysts for
      hydrogen evolution reaction (HER), the accumulation of hydrogen gas bubbles
      produced on the catalyst surface has been rather poorly addressed. The bubbles
      block the surface of the electrode, thus resulting in poor performance even when
      excellent electrocatalysts are used. In this study, we show that vertically grown
      graphene nanohills (VGNHs) possess an excellent capability to quickly disengage
      the produced hydrogen gas bubbles from the electrode surface, and thus exhibit
      superaerophobic properties. To compensate for the poor electrolytic properties of
      graphene toward HER, the graphene surface was modified with WS2 nanoparticles to
      accelerate the water-splitting process by using this hybrid catalyst (VGNHs-WS2).
      For comparison purposes, WS2 nanoparticles were also deposited on the flat
      graphene (FG) surface. Because of its superior superaerophobic properties, VGNHs
      WS2 outperformed FG-WS2 in terms of both catalytic activity toward the HER and
      superaerophobicity. Furthermore, VGNHs-WS2 exhibited a low onset potential (36 mV
      compared to 288 mV for FG-WS2) and long-term stability in the HER over an
      extended period of 20 h. This study provides an efficient way to utilize highly
      conductive and superaerophobic VGNHs as support materials for intrinsic
      semiconductors, such as WS2, to simultaneously achieve superaerophobicity and
      high catalytic activity.

PMID- 29179533
TI  - Missing Linker Defects in a Homochiral Metal-Organic Framework: Tuning the Chiral
      Separation Capacity.
AB  - Efficient chiral separation remains a very challenging task due to the identical
      physical and chemical properties of the enantiomers of a molecule. Enantiomers
      only behave differently from each other in the presence of other chiral species.
      Homochiral metal-organic frameworks (MOFs) have received much attention for their
      promising enantioseparation properties. However, there are still challenges to
      overcome in this field such as high enantiomeric separation. Structural defects
      play an important role in the properties of MOFs and can significantly change the
      pore architecture. In this work, we introduced missing linker defects into a
      homochiral metal-organic framework [Zn2(bdc)(l-lac)(dmf)] (ZnBLD; bdc = 1,4
      benzenedicarboxylic acid, l-lac = l-lactic acid, dmf = N,N'-dimethylformamide)
      and observed an increase in enantiomeric excess for 1-phenylethanol of 35% with
      the defective frameworks. We adjusted the concentration of monocarboxylic acid
      ligand l-lactic acid by varying the ratio of Zn2+ to ligand from 0.5 to 0.85
      mmol. Additionally, a defective framework was synthesized with propanoic acid as
      modulator. In order to elucidate the correlation between defects and enantiomeric
      excess, five characterization techniques (FTIR, TGA, 1H NMR, ICP, and PXRD) were
      employed. Full width at half-maximum analysis (fwhm) was performed on the powder
      X-ray diffraction traces and showed that the higher concentration of
      monocarboxylic acid MOFs were isostructural but suffered from increased fwhm
      values.

PMID- 29179534
TI  - Simultaneous Suppression of Metal Corrosion and Electrolyte Decomposition by
      Graphene Oxide Protective Coating in Magnesium-Ion Batteries: Toward a 4-V-Wide
      Potential Window.
AB  - Despite remarkable developments in electrolyte systems over the past 2 decades,
      magnesium-ion batteries still suffer from corrosion susceptibility and low anodic
      limits. Herein we describe how graphene oxide (GO), coated onto non-noble metals
      (Al, Cu, and stainless steel) via electrophoretic deposition, can solve this
      problem. In all phenyl complex electrolytes, GO coating results in a significant
      suppression of corrosion and extends the anodic limits (up to 4.0 V vs Mg/Mg2+)
      with no impact on reversible Mg plating/stripping reactions. The same effect of
      GO coating is also established in magnesium aluminum chloride complex
      electrolytes. This remarkable improvement is associated with the electrostatic
      interaction between the ionic charges of electrolytes and the surface-functional
      groups of GO. In addition, GO coating does not aggravate the cathode performance
      of Mo6S8, which allows the use of non-noble metals as current collectors. We also
      discuss the role of GO in increasing anodic limits when it is hybridized with
      alpha-MnO2.

PMID- 29179535
TI  - Differential Ion Mobility Separations in the Low-Pressure Regime.
AB  - Ion mobility spectrometry (IMS) in conjunction with mass spectrometry (MS) has
      emerged as a powerful platform for biological and environmental analyses. An
      inherent advantage of differential or field asymmetric waveform IMS (FAIMS) based
      on the derivative of mobility vs electric field over linear IMS based on absolute
      mobility is much greater orthogonality to MS. Effective coupling of linear IMS to
      MS and diverse IMS/MS arrangements and modalities impossible at ambient buffer
      gas pressure were enabled at much reduced pressures. In contrast, FAIMS devices
      operate at or near atmospheric pressure, which complicated integration with MS.
      Here, we show FAIMS at ~15-30 Torr using a planar-gap stage within the MS
      instrument envelope. Fields up to ~300 Td permitted by the Paschen law at these
      pressures greatly raise the separation speed, providing fair resolution in ~10 ms
      and FAIMS scans in under 5 s. Rapid separation and efficient ion collection at
      low pressure minimize losses in the FAIMS step. Separations for key analyte
      classes and their dependences on electric field mirror those at ambient pressure.
      The potential for proteomics is demonstrated by separations of isomeric peptides
      with variant localization of post-translational modifications.

PMID- 29179536
TI  - Carbon Nanotube Dispersion in Solvents and Polymer Solutions: Mechanisms,
      Assembly, and Preferences.
AB  - Debundling and dispersion of carbon nanotubes (CNTs) in polymer solutions play a
      major role in the preparation of carbon nanofibers due to early effects on
      interfacial ordering and mechanical properties. A roadblock toward ultrastrong
      fibers is the difficulty to achieve homogeneous dispersions of CNTs in
      polyacrylonitrile (PAN) and poly(methyl methacrylate) (PMMA) precursor solutions
      in solvents such as dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAc), and
      N,N-dimethylformamide (DMF). In this contribution, molecular dynamics simulations
      with accurate interatomic potentials for graphitic materials that include virtual
      pi electrons are reported to analyze the interaction of pristine single wall CNTs
      with the solvents and polymer solutions at 25  degrees C. The results explain the
      barriers toward dispersion of SWCNTs and quantify CNT-solvent, polymer-solvent,
      as well as CNT-polymer interactions in atomic detail. Debundling of CNTs is
      overall endothermic and unfavorable with dispersion energies of +20 to +30 mJ/m2
      in the pure solvents, + 20 to +40 mJ/m2 in PAN solutions, and +20 to +60 mJ/m2 in
      PMMA solutions. Differences arise due to molecular geometry, polar, van der
      Waals, and CH-pi interactions. Among the pure solvents, DMF restricts CNT
      dispersion less due to the planar geometry and stronger van der Waals
      interactions. PAN and PMMA interact favorably with the pure solvents with
      dissolution energies of -0.7 to -1.1 kcal per mole monomer and -1.5 to -2.2 kcal
      per mole monomer, respectively. Adsorption of PMMA onto CNTs is stronger than
      that of PAN in all solvents as the molecular geometry enables more van der Waals
      contacts between alkyl groups and the CNT surface. Polar side groups in both
      polymers prefer interactions with the polar solvents. Higher polymer
      concentrations in solution lead to polymer aggregation via alkyl groups and
      reduce adsorption onto CNTs. PAN and PMMA solutions in DMSO and dilute solutions
      in DMF support CNT dispersion more than other combinations whereby the polymers
      significantly adsorb onto CNTs in DMSO solution. The observations by molecular
      simulations are consistent with available experimental data and solubility
      parameters and aid in the design of carbon nanofibers. The methods can be applied
      to other multiphase graphitic materials.

PMID- 29179537
TI  - Evidence for Electron Transfer in the Reactions of Hydrated Monovalent First-Row
      Transition-Metal Ions M(H2O)n+, M = V, Cr, Mn, Fe, Co, Ni, Cu, and Zn, n < 40,
      toward 1-Iodopropane.
AB  - Hydrated metal ions in the gas phase serve as model systems to investigate the
      impact of hydration on the chemistry of monovalent transition-metal centers. As a
      prototypical organometallic reaction involving electron transfer, the reactions
      of M(H2O)n+, M = V, Cr, Mn, Fe, Co, Ni, Cu, and Zn, n < 40, with C3H7I are
      studied by Fourier transform ion cyclotron resonance mass spectrometry. While no
      reaction was observed for vanadium, three different reactions were observed with
      the other metals, two of them involving the oxidation of the metal ion. Ligand
      exchange occurs for all metals except zinc. This reaction is sensitive to the
      size of the solvation shell and is observed predominantly for small cluster
      sizes. For Cr, Co, and Zn, the metal center is oxidized with formation of MI+
      ions. The formation of [MC3H6(C3H7I)2]+, M = Co+, Ni+, proceeds most likely via
      oxidative addition of C3H7I to the metal ion via insertion into the C-I bond,
      followed by reductive elimination of HI. For Cu+, this reaction seems to stop
      after the insertion of the metal into the C-I bond, resulting in
      Cu(C3H7I)(H2O)n+. The reactions are compared with earlier studies on electron
      transfer involving hydrated metal centers.

PMID- 29179538
TI  - Three-Dimensional Ionic Covalent Organic Frameworks for Rapid, Reversible, and
      Selective Ion Exchange.
AB  - Covalent organic frameworks (COFs) have emerged as functional materials for
      various potential applications. However, the availability of three-dimensional
      (3D) COFs is still limited, and nearly all of them exhibit neutral porous
      skeletons. Here we report a general strategy to design porous positively charged
      3D ionic COFs by incorporation of cationic monomers in the framework. The
      obtained 3D COFs are built of 3-fold interpenetrated diamond net and show
      impressive surface area and CO2 uptakes. The ion-exchange ability of 3D ionic
      COFs has been highlighted by reversible removal of nuclear waste model ions and
      excellent size-selective capture for anionic pollutants. This research thereby
      provides a new perspective to explore 3D COFs as a versatile type of ion-exchange
      materials.

PMID- 29179539
TI  - Interplay between CN- Ligands and the Secondary Coordination Sphere of the H
      Cluster in [FeFe]-Hydrogenases.
AB  - The catalytic cofactor of [FeFe]-hydrogenses (H-cluster) is composed of a generic
      cubane [4Fe-4S]-cluster (4FeH) linked to a binuclear iron-sulfur cluster (2FeH)
      that has an open coordination site at which the reversible conversion of protons
      to molecular hydrogen occurs. The (2FeH) subsite features a diatomic coordination
      sphere composed of three CO and two CN- ligands affecting its redox properties
      and providing excellent probes for FTIR spectroscopy. The CO stretch vibrations
      are very sensitive to the redox changes within the H-cluster occurring during the
      catalytic cycle, whereas the CN- signals seem to be relatively inert to these
      effects. This could be due to the more structural role of the CN- ligands tightly
      anchoring the (2FeH) unit to the protein environment through hydrogen bonding. In
      this work we explore the effects of structural changes within the secondary
      ligand sphere affecting the CN- ligands on FTIR spectroscopy and catalysis. By
      comparing the FTIR spectra of wild-type enzyme and two mutagenesis variants, we
      are able to assign the IR signals of the individual CN- ligands of the (2FeH)
      site for different redox states of the H-cluster. Moreover, protein film
      electrochemistry reveals that targeted manipulation of the secondary coordination
      sphere of the proximal CN- ligand (i.e., closest to the (4FeH) site) can affect
      the catalytic bias. These findings highlight the importance of the protein
      environment for re-adjusting the catalytic features of the H-cluster in
      individual enzymes and provide valuable information for the design of artificial
      hydrogenase mimics.

PMID- 29179540
TI  - Unified Total Synthesis of Stemoamide-Type Alkaloids by Chemoselective Assembly
      of Five-Membered Building Blocks.
AB  - A unified total synthesis of stemoamide-type alkaloids is reported. Our synthetic
      approach features the chemoselective convergent assembly of five-membered
      building blocks via stemoamide as the common precursor to tetracyclic natural
      products. The synthesis consists of two successive coupling reactions of the
      three five-membered building blocks. The first coupling reaction is the
      vinylogous Michael addition/reduction sequence, which enables the gram-scale
      synthesis of stemoamide. The second coupling reaction is a chemoselective
      nucleophilic addition to stemoamide. While the lactone-selective nucleophilic
      addition to stemoamide affords saxorumamide and isosaxorumamide, the lactam
      selective reductive nucleophilic addition leads to the formation of stemonine.
      Both chemoselective nucleophilic additions enable direct modification of
      stemoamide, resulting in highly concise and efficient total syntheses of the
      stemoamide-type alkaloids.

PMID- 29179541
TI  - 1H NMR Relaxometry and Diffusometry Study of Magnetic and Nonmagnetic Ionic
      Liquid-Based Solutions: Cosolvent and Temperature Effects.
AB  - In this work, 1H NMR relaxometry and diffusometry as well as viscometry
      experiments were carried out as a means to study the molecular dynamics of
      magnetic and nonmagnetic ionic liquid-based systems. In order to evaluate the
      effect of a cosolvent on the superparamagnetic properties observed for Aliquat
      iron-based magnetic ionic liquids, mixtures comprising different concentrations,
      1% and 10% (v/v), of DMSO-d6 were prepared and studied. The results for both
      magnetic and nonmagnetic systems were consistently analyzed an suggest that, when
      at low concentrations, DMSO-d6 promotes more structured ionic arrangements, thus
      enhancing these superparamagnetic properties. Furthermore, the analysis of
      temperature and water concentration effects allowed to conclude that neither one
      of these variables significantly affected the superparamagnetic properties of the
      studied magnetic ionic liquids.

PMID- 29179542
TI  - Perspective on Biotransformation and De Novo Biosynthesis of Licorice
      Constituents.
AB  - Licorice, an important herbal medicine, is derived from the dried roots and
      rhizomes of Glycyrrhiza genus plants. It has been widely used in food,
      pharmaceutical, tobacco, and cosmetics industries with high economic value.
      However, overexploitation of licorice resources has severely destroyed the local
      ecology. Therefore, producing bioactive compounds of licorice through the
      biotransformation and bioengineering methods is a hot spot in recent years. In
      this perspective, we comprehensively summarize the biotransformation of licorice
      constituents into high-value-added derivatives by biocatalysts. Furthermore,
      successful cases and the strategies for de novo biosynthesizing compounds of
      licorice in microbes have been summarized. This paper will provide new insights
      for the further research of licorice.

PMID- 29179543
TI  - Effects of Selenite on Unicellular Green Microalga Chlorella pyrenoidosa:
      Bioaccumulation of Selenium, Enhancement of Photosynthetic Pigments, and Amino
      Acid Production.
AB  - Microalgae were studied as function bioaccumulators of selenium (Se) for food and
      feed supplement. To investigate the bioaccumulation of Se and its effects on the
      unicellular green alga Chlorella pyrenoidosa, the algal growth curve,
      fluorescence parameters, antioxidant enzyme activity, and fatty acid and amino
      acid profiles were examined. We found that Se at low concentrations (<=40 mg L-1)
      positively promoted algal growth and inhibited lipid peroxidation and
      intracellular reactive oxygen species. The antioxidative effect was associated
      with an increase in the levels of glutathione peroxidase, catalase, linolenic
      acid, and photosynthetic pigments. Meanwhile, a significant increase in amino
      acid and organic Se content was also detected in the microalgae. In contrast, we
      found opposite effects in C. pyrenoidosa exposed to >60 mg L-1 Se. The
      antioxidation and toxicity appeared to be correlated with the bioaccumulation of
      excess Se. These results provide a better understanding of the effect of Se on
      green microalgae, which may help in the development of new technological
      applications for the production of Se-enriched biomass from microalgae.

PMID- 29179544
TI  - Privileged Role of Thiolate as the Axial Ligand in Hydrogen Atom Transfer
      Reactions by Oxoiron(IV) Complexes in Shaping the Potential Energy Surface and
      Inducing Significant H-Atom Tunneling.
AB  - An H/D kinetic isotope effect (KIE) of 80 is found at -20  degrees C for the
      oxidation of 9,10-dihydroanthracene by [FeIV(O)(TMCS)]+, a complex supported by
      the tetramethylcyclam (TMC) macrocycle with a tethered thiolate. This KIE value
      approaches that previously predicted by DFT calculations. Other
      [FeIV(O)(TMC)(anion)] complexes exhibit values of 20, suggesting that the
      thiolate ligand of [FeIV(O)(TMCS)]+ plays a unique role in facilitating
      tunneling. Calculations show that tunneling is most enhanced (a) when the bond
      asymmetry between C-H bond breaking and O-H bond formation in the transition
      state is minimized, and (b) when the electrostatic interactions in the O---H---C
      moiety are maximal. These two factors-which peak for the best electron donor, the
      thiolate ligand-afford a slim and narrow barrier through which the H-atom can
      tunnel most effectively.

PMID- 29179545
TI  - Effect of Counterions on the Self-Assembly of Polystyrene-Polyphosphonium Block
      Copolymers.
AB  - The ability to manipulate block copolymers on the nanoscale has led to many
      scientific and technological advances. These include nanoscale ordered bulk and
      thin films and also solution phase components; these are promising materials for
      making smaller ordered electronics, selective membranes, and also biomedical
      applications. The ability to manipulate block copolymer material architectures on
      such small scales has risen from thorough investigations into the properties that
      affect the architectures. Polyelectrolytes are an important class of polymers
      that are used to make amphiphilic block copolymers. In this context the authors
      synthesized polystyrene-b-polyphosphonium block copolymers with different anions
      coordinated to the polyphosphonium block in order to study the effect of the
      anion on the aqueous self-assembly of the polymers. The anions play an important
      role in the solubility of the monomeric materials which results in differences in
      the self-assembly observed through dynamic light scattering and transmission
      electron microscopy.

PMID- 29179546
TI  - Reference Gene Selection and Prednisolone Target Gene Expression in Adipose
      Tissues of Friesian Cattle.
AB  - Corticosteroids are frequently used in livestock production, and their use is
      permitted by the European Union for therapeutic purposes only. However, small
      doses of corticosteroids are often administered in meat-producing animals to
      improve zootechnical performance. Prednisolone is one of the most commonly used
      corticosteroids with a growth-promoting purpose in animal husbandry. This study
      proposes to identify a gene whose expression is significantly regulated by
      prednisolone in visceral and subcutaneous adipose tissues. The analysis was
      conducted on Friesian cattle treated with prednisolone (30 mg day-1). The
      reference gene expression stability and optimal number for gene expression
      normalization were calculated. Family with sequence similarity 107 member A
      (FAM107A) and pyruvate dehydrogenase kinase 4 are the prednisolone target genes
      identified in adipose tissue. FAM107A was downregulated by ~2.9-fold by
      prednisolone in subcutaneous adipose tissue. This result suggests that FAM107A
      could be a possible indirect biomarker of prednisolone treatment in cattle and
      encourages a deeper investigation in this direction.

PMID- 29179547
TI  - Dietary Alfalfa and Calcium Salts of Long-Chain Fatty Acids Alter Protein
      Utilization, Microbial Populations, and Plasma Fatty Acid Profile in Holstein
      Freemartin Heifers.
AB  - This study presented the effects of alfalfa and calcium salts of long-chain fatty
      acids (CSFA) on feed intake, apparent digestibility, rumen fermentation,
      microbial community, plasma biochemical parameters, and fatty acid profile in
      Holstein freemartin heifers. Eight Holstein freemartin heifers were randomly
      divided into a 4 * 4 Latin Square experiment with 2 * 2 factorial diets, with or
      without alfalfa or CSFA. Dietary supplementation of CSFA significantly increased
      the apparent digestibility of dry matter, crude protein, neutral detergent fiber,
      organic matter, and significantly reduced N retention (P < 0.05). CSFA increased
      the concentration of ammonia nitrogen in the ruminal fluid (P < 0.05), but
      alfalfa increased the concentration of valerate and isovalerate (P < 0.05). CSFA
      increased the concentration of ammonia nitrogen and the relative population of
      Streptococcus bovis in the rumen (P < 0.05) and inhibited the relative population
      of Ruminococcus flavefaciens, methanogens, and protozoa (P < 0.05). Alfalfa
      instead of Leymus chinensis increased the relative population of Butyrivibrio
      fibrisolvens and Ruminobacter amylophilus in the rumen (P < 0.05) and reduced the
      relative population of the Ruminococcus albus and Megasphaera elsdenii (P <
      0.05). Supplemental CSFA increased the concentration of cholesterol and low
      density lipoprotein cholesterol in the plasma (P < 0.05). And it also altered the
      composition of fatty acids in the plasma, which was expressed in reducing
      saturated fatty acid (SigmaSFA) ratio and C14-C17 fatty acids proportion except
      C16:0 (P < 0.05) and increasing the proportion of polyunsaturated fatty acid
      (SigmaPUFA) and unsaturated fatty acid (SigmaUFA) (P < 0.05). The results showed
      that alfalfa and CSFA had interaction effect on the apparent digestibility of
      ether extracts, plasma triglyceride concentration, isobutyrate concentration, and
      Ruminococcus albus relative abundance in the rumen. It was concluded that alfalfa
      substituting Leymus chinensis did not change the apparent digestibility of
      nutrients in the final stage of fattening Holstein freemartin heifers, while CSFA
      increased the cholesterol and the proportion of unsaturated fatty acids in
      plasma. Alfalfa and CSFA had mutual interaction effect on fat digestion and
      plasma triglycerides.

PMID- 29179548
TI  - Molecular Iridium Complexes in Metal-Organic Frameworks Catalyze CO2
      Hydrogenation via Concerted Proton and Hydride Transfer.
AB  - Molecular iridium catalysts immobilized in metal-organic frameworks (MOFs) were
      positioned in the condensing chamber of a Soxhlet extractor for efficient CO2
      hydrogenation. Droplets of hot water seeped through the MOF catalyst to create
      dynamic gas/liquid interfaces which maximize the contact of CO2, H2, H2O, and the
      catalyst to achieve a high turnover frequency of 410 h-1 under atmospheric
      pressure and at 85  degrees C. H/D kinetic isotope effect measurements and
      density functional theory calculations revealed concerted proton-hydride transfer
      in the rate-determining step of CO2 hydrogenation, which was difficult to unravel
      in homogeneous reactions due to base-catalyzed H/D exchange.

PMID- 29179549
TI  - Selective Hydrogen Isotope Separation via Breathing Transition in MIL-53(Al).
AB  - Breathing of MIL-53(Al), a flexible metal-organic framework (MOF), leads to
      dynamic changes as narrow pore (np) transitions to large pore (lp). During the
      flexible and reversible transition, the pore apertures are continuously adjusted,
      thus providing the tremendous opportunity to separate mixtures of similar-sized
      and similar-shaped molecules that require precise pore tuning. Herein, for the
      first time, we report a strategy for effectively separating hydrogen isotopes
      through the dynamic pore change during the breathing of MIL-53(Al), a
      representative of flexible MOFs. The experiment shows that the selectivity for D2
      over H2 is strongly related to the state of the pore structure of MIL-53(Al). The
      highest selectivity (SD2/H2 = 13.6 at 40 K) was obtained by optimizing the
      exposure temperature, pressure, and time to systematically tune the pore state of
      MIL-53(Al).

PMID- 29179550
TI  - Quercetin Oxidation Paradoxically Enhances its Antioxidant and Cytoprotective
      Properties.
AB  - Quercetin oxidation is generally believed to ultimately result in the loss of its
      antioxidant properties. To test this assertion, quercetin oxidation was induced,
      and after each of its major metabolites was identified and isolated by HPLC-DAD
      ESI-MS/MS, the antioxidant (dichlorodihydrofluorescein oxidation-inhibiting) and
      cytoprotective (LDH leakage-preventing) properties were evaluated in Hs68 and
      Caco2 cells exposed to indomethacin. Compared to quercetin, the whole mixture of
      metabolites (QOX) displayed a 20-fold greater potency. After resolution of QOX
      into 12 major peaks, only one (peak 8), identified as 2,5,7,3',4'-pentahydroxy
      3,4-flavandione or its 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)
      benzofuranone tautomer, could account for the antioxidant and cytoprotective
      effects afforded QOX. Peak 8 exerted such effects at a 50 nM concentration,
      revealing a potency 200-fold higher than that of quercetin. The effects of peak 8
      were seen regardless of whether it was added to the cells 40 min before or
      simultaneously with the oxygen-reactive species-generating agent, suggesting an
      intracellular ability to trigger early antioxidant responses. Thus, the present
      study is the first to reveal that in regard to the intracellular actions of
      quercetin, attention should be extended toward some of its oxidation products.

PMID- 29179551
TI  - Synthetic Access to Noncanonical Strigolactones: Syntheses of Carlactonic Acid
      and Methyl Carlactonoate.
AB  - Strigolactones are plant hormones regulating essential stages of a plant's
      development. Their low natural abundance combined with a low chemical stability
      significantly hampered the detailed investigation of their biological activity.
      Noncanonical strigolactones lack the fused tricyclic ABC-ring system commonly
      present in canonical-type strigolactones but feature an open-chain unit linking
      structurally diverse A-ring moieties to the butenolide D-ring. We herein present
      an efficient synthetic access to enantiomerically pure noncanonical
      strigolactones by a Stille cross-coupling approach to forge the central diene
      moiety and demonstrate this strategy by syntheses of natural products methyl
      carlactonoate and carlactonic acid. Furthermore, a synthetic access to deuterium
      labeled analogues of these natural products has been developed.

PMID- 29179552
TI  - Universal Method for Creating Hierarchical Wrinkles on Thin-Film Surfaces.
AB  - One of the most interesting topics in physical science and materials science is
      the creation of complex wrinkled structures on thin-film surfaces because of
      their several advantages of high surface area, localized strain, and stress
      tolerance. In this study, a significant step was taken toward solving limitations
      imposed by the fabrication of previous artificial wrinkles. A universal method
      for preparing hierarchical three-dimensional wrinkle structures of thin films on
      a multiple scale (e.g., nanometers to micrometers) by sequential wrinkling with
      different skin layers was developed. Notably, this method was not limited to
      specific materials, and it was applicable to fabricating hierarchical wrinkles on
      all of the thin-film surfaces tested thus far, including those of metals, two
      dimensional and one-dimensional materials, and polymers. The hierarchical
      wrinkles with multiscale structures were prepared by sequential wrinkling, in
      which a sacrificial layer was used as the additional skin layer between
      sequences. For example, a hierarchical MoS2 wrinkle exhibited highly enhanced
      catalytic behavior because of the superaerophobicity and effective surface area,
      which are related to topological effects. As the developed method can be adopted
      to a majority of thin films, it is thought to be a universal method for enhancing
      the physical properties of various materials.

PMID- 29179553
TI  - How Interatomic Steps in the Exact Kohn-Sham Potential Relate to Derivative
      Discontinuities of the Energy.
AB  - Accurate density functional calculations hinge on reliable approximations to the
      unknown exchange-correlation (xc) potential. The most popular approximations
      usually lack features of the exact xc potential that are important for an
      accurate prediction of the fundamental gap and the distribution of charge in
      complex systems. Two principal features in this regard are the spatially uniform
      shift in the potential, as the number of electrons infinitesimally surpasses an
      integer, and the spatial steps that form, for example, between the atoms of
      stretched molecules. Although both aforementioned concepts are well known, the
      exact relationship between them remained unclear. Here we establish this
      relationship via an analytical derivation. We support our result by numerically
      solving the many-electron Schrodinger equation to extract the exact Kohn-Sham
      potential and directly observe its features. Spatial steps in the exact xc
      potential of a full configuration-interaction (FCI) calculation of a molecule are
      presented in three dimensions.

PMID- 29179554
TI  - Comparison between Experimental and Broken Symmetry Density Functional Theory (BS
      DFT) Calculated Electron Paramagnetic Resonance (EPR) Parameters of the S2 State
      of the Oxygen-Evolving Complex of Photosystem II in Its Native (Calcium) and
      Strontium-Substituted Form.
AB  - A comparison between experimental and Broken Symmetry Density Functional theory
      (BS-DFT) calculated hyperfine couplings for the S2 state of the oxygen-evolving
      complex (OEC) has been performed. The effect of Ca substitution by Sr combined
      with the protonation state of two terminal hydroxo or aqua ligands, W1 and W2, on
      the calculated hyperfine couplings of 55Mn, 13C, 14N, 17O, and 1H nuclei has been
      investigated. Our findings show best agreement with experiment for OEC models
      which contain a hydroxide group at the W2 position and a water molecule at W1.
      For this model the agreement between calculated and experimental data for all
      hyperfine couplings is excellent. Models with a hydroxide group at W1 are
      particularly poor models. Sr substitution has a minor influence on calculated
      hyperfine couplings in agreement with experimental determinations. The
      sensitivity of the hyperfine couplings to relatively minor changes in the OEC
      structure demonstrates the power of this methodology in refining the details of
      its steric and electronic structure which is an essential step in formulating a
      complete mechanism for water oxidation by the OEC.

PMID- 29179555
TI  - Simultaneous Analysis of Malondialdehyde, 4-Hydroxy-2-hexenal, and 4-Hydroxy-2
      nonenal in Vegetable Oil by Reversed-Phase High-Performance Liquid
      Chromatography.
AB  - A group of toxic aldehydes such as, malondialdehyde (MDA), 4-hydroxy-2-hexenal
      (HHE), and 4-hydroxy-2-nonenal (HNE) have been found in various vegetable oils
      and oil-based foods. Then simultaneous determination of them holds a great need
      in both the oil chemistry field and food field. In the present study, a simple
      and efficient analytical method was successfully developed for the simultaneous
      separation and detection of MDA, HHE, and HNE in vegetable oils by reversed-phase
      high-performance liquid chromatography (RP-HPLC) coupled with photodiode array
      detector (PAD) at dual-channel detection mode. The effect of various experimental
      factors on the extraction performance, such as coextraction solvent system,
      butylated hydroxytoluene addition, and trichloroacetic acid addition were
      systematically investigated. Results showed that the linear ranges were 0.02
      10.00 MUg/mL for MDA, 0.02-4.00 MUg/mL for HHE, and 0.03-4.00 MUg/mL for HNE with
      the satisfactory correlation coefficient of >0.999 for all detected aldehydes.
      The limit of detection (LOD) and limit of quantification (LOQ) of MDA, HHE, and
      HNE were ~0.021and 0.020 MUg/mL, ~0.009 and 0.020 MUg/mL, and ~0.014 and 0.030
      MUg/mL, respectively. Their recoveries were 99.64-102.18%, 102.34-104.61%, and
      98.87-103.04% for rapeseed oil and 96.38-98.05%, 96.19-101.34%, and 96.86-99.04%
      for French fries, separately. Under the selected conditions, the developed
      methods was successfully applied to the simultaneous determination of MDA, HHE,
      and HNE in different tested vegetable oils. The results indicated that this
      method could be employed for the quality assessment of vegetable oils.

PMID- 29179556
TI  - Long-Range Changes in Neurolysin Dynamics Upon Inhibitor Binding.
AB  - Crystal structures of neurolysin, a zinc metallopeptidase, do not show a
      significant conformational change upon the binding of an allosteric inhibitor.
      Neurolysin has a deep channel where it hydrolyzes a short neuropeptide
      neurotensin to create inactive fragments and thus controls its level in the
      tissue. Neurolysin is of interest as a therapeutic target since changes in
      neurotensin level have been implicated in cardiovascular disorders, neurological
      disorders, and cancer, and inhibitors of neurolysin have been developed. An
      understanding of the dynamical and structural differences between apo and
      inhibitor-bound neurolysin will aid in further design of potent inhibitors and
      activators. For this purpose, we performed several molecular dynamics (MD)
      simulations for both apo and inhibitor-bound neurolysin. A machine learning
      method (Linear Discriminant Analysis) is applied to reveal differences between
      the apo and inhibitor-bound ensembles in an automated way, and large differences
      are observed on residues that are far from both the active site and the inhibitor
      binding site. The effects of inhibitor binding on the collective motions of
      neurolysin are extensively analyzed and compared using both Principal Component
      Analysis and Elastic Network Model calculations. We find that inhibitor binding
      induces additional low-frequency motions that are not observed in the apo form.
      ENM also reveals changes in inter- and intradomain communication upon binding.
      Furthermore, differences are observed in the inhibitor-bound neurolysin contact
      network that are far from the active site, revealing long-range allosteric
      behavior. This study also provides insight into the allosteric modulation of
      other neuropeptidases with similar folds.

PMID- 29179557
TI  - Displacement of Bax by BMF Mediates STARD13 3'UTR-Induced Breast Cancer Cells
      Apoptosis in an miRNA-Depedent Manner.
AB  - The balance of pro- and antiapoptotic gene expression programs dominates the
      apoptotic progress of cancer cells. We previously demonstrated that STARD13 3'UTR
      suppressed breast cancer metastasis via inhibiting epithelial-mesenchymal
      transition (EMT). However, the roles of STARD13 3'UTR in breast cancer apoptosis
      remain elusive. Here, we identified that STARD13 3'UTR promoted cell apoptosis in
      vitro and in vivo. Mechanistically, STARD13 3'UTR acted as a ceRNA for BMF (Bcl-2
      modifying factor), thus increasing BMF expression in an miRNA-dependent manner.
      Meanwhile, STARD13 3'UTR enhanced the interaction of BMF/Bcl-2 to release Bax
      (Bcl-2 associated X protein) in breast cancer cells. Finally, we verified the
      ceRNA relationship between STARD13 and BMF in vivo. Collectively, these findings
      suggest that STARD13 3'UTR could act as a ceRNA for BMF to promote apoptosis and
      recognize STARD13 3'UTR as a potential therapeutic target in breast cancer cells.

PMID- 29179558
TI  - Physicochemical characteristics of the Lasiococca comberi Haines seeds.
AB  - Physicochemical characteristics and fatty acid composition of Lasiococca comberi
      Haines (Euphorbiaceae), an endangered forest tree species, were determined for
      the first time. The oil, protein, crude fibre and carbohydrate contents in seeds
      were 41.5, 13.8, 22.2 and 11.6%, respectively. The refractive index, pH, specific
      gravity, saponification value, iodine value, peroxide value and p-anisidine value
      of seed oil were 1.4781, 6.4, 0.9, 178.4 mg KOH/g, 196 g I2/100 g of oil, 5.1 mEq
      O2/kg and 188.4, respectively. The predominant fatty acids were linolenic acid
      (65.3%), oleic acid (13.8%), linoleic acid (7.1%) and palmitic acid (5.3%). HPLC
      analysis revealed the presence of alpha-tocopherol (13.2 mg/100 g) and gamma
      tocopherol (6.3 mg/100 g) as the major tocopherols. The results indicated that L.
      comberi seed oil can be classified as drying oil having possible applications in
      different industries and as an important dietary source of omega-3 fatty acids.

PMID- 29179559
TI  - Does Exercise During Pregnancy Affect Placental Weight?: A Randomized Clinical
      Trial.
AB  - Placental weight (PW) is a measure commonly used to summarize growth and aspects
      of placental function. In a normal pregnancy, it is reasonable to assume that PW
      is related to aspects of the functional capacity of the placenta. The placenta,
      as the site for all maternal-fetal oxygen and nutrient exchange, influences birth
      weight and is thus central to a successful pregnancy outcome. PW is the most
      common way to characterize placental growth, which relates to placental function.
      With physical exercise becoming an integral part of life for many women, the
      question of whether exercise during pregnancy has an adverse effect on the
      growing fetus is very important. The aim was to examine the influence of an
      aerobic exercise program throughout pregnancy on PW among healthy pregnant women.
      A randomized control trial was used (registration trial number: NCT02420288).
      Women were randomized into an exercise group (EG; n = 33) or a control group (CG;
      n = 32) that received standard care. The EG trained 3 days/week (55-60
      min/session) from gestational Weeks 9-11 until Weeks 38-39. The 85 training
      sessions involved aerobic, muscular and pelvic floor strength, and flexibility
      exercises. PW and other pregnancy outcomes were measured. There was high
      attendance to the exercise program, and no differences in the PW at delivery were
      observed between study groups (CG = 493.2 +/- 119.6 g vs. EG = 495.4 +/- 150 g, p
      = .95). A regular, supervised exercise program throughout pregnancy does not
      affect the PW in healthy pregnant women.

PMID- 29179560
TI  - The Association Between Hospital Characteristics and Nonresponse in Organization
      Survey: An Analysis of the National Healthcare Establishment and Workforce Survey
      in Malaysia.
AB  - In any survey where some of the invited participants fail to respond estimates
      may be biased. The literature on survey nonresponse is substantial, and the
      intellectual focus has typically been on the nonresponse of individuals. An
      important yet less scrutinized area in the analysis of nonresponse is in
      organizational surveys, particularly surveys of health-care organizations. This
      study used data from the 2010 National Healthcare Establishment and Workforce
      Survey in Malaysia to examine the relationship between a set of measurable
      hospital attributes and their probability of survey response and the relationship
      between this probability and the differences in survey estimates. We found that
      readily measurable hospital characteristics such as size and geographical
      location are useful predictors of survey response likelihood. Larger hospitals
      and hospitals located in less developed geographical regions responded more
      favorably than their counterparts. We have also illustrated that the resulting
      response pattern affected some key survey estimates. These findings have the
      potential to extend our understanding of nonresponse to organization surveys in
      the health-care sector, potentially allow for the prediction of nonresponse, and
      help researchers to identify profiles of "reluctant responders" before a survey
      commences, so that additional engagement strategies may be used.

PMID- 29179561
TI  - Development and Validation of the Activities of Daily Living Short Form for
      Community-Dwelling Korean Stroke Survivors.
AB  - This study developed and validated a short form (SF) using activities of daily
      living (ADL) outcome measures from the Korea National Health and Nutrition
      Examination Survey (KNHANES) that can minimize survey administration burden for
      clinicians. This study utilized secondary data from the 2005 KNHANES with 422
      community-dwelling stroke survivors. The KNHANES data were collected from April
      to June 2005 in South Korea. We created a 7-item SF from the 17 ADL questions in
      the survey using item response theory (IRT) methodologies. The precision and
      validity of the SF were compared to the full questionnaire of ADL items and the
      EuroQol-5D total score. Among the 17 ADL questions, 14 questions demonstrated
      unidimensional construct validity. Using IRT methodologies, a set of 7 items were
      selected from the full bank. The 7-item SF demonstrated good psychometric
      properties: high correlation with the full bank ( r = .975, p < .001), good
      internal consistency (Cronbach's alpha = .93), and a high correlation with the
      EuroQol-5D total score ( r = .678, p < .001). These findings indicate that a well
      developed SF can precisely measure ADL performance capacity for stroke survivors
      compared to the full item bank, which is expected to reduce the administration
      burden of the KNHANES.

PMID- 29179562
TI  - Effects of Support Interventions in Women Hospitalized With Preterm Labor.
AB  - This study was to examine the effects of support interventions on anxiety,
      depression, and quality of life in women hospitalized with preterm labor. A
      randomized, single-blind experimental design was used. Participants were
      recruited from maternity wards of one medical center in Taiwan. The control group
      ( n = 103) received routine nursing care, and intervention group ( n = 140)
      received interventional support during hospitalization. The Beck Anxiety
      Inventory, Edinburgh Postnatal Depression Scale, and Quality of Life Enjoyment
      and Satisfaction Questionnaire were used at admission and 2 weeks of
      hospitalization. For the control group, anxiety and depression scores increased
      significantly and quality of life decreased 2 weeks after hospitalization.
      Participants who received 2 weeks of support intervention had significantly lower
      anxiety and depression scores than controls. Thus, clinical nurses can offer
      support interventions to improve anxiety and depression for women with preterm
      labor during hospitalization.

PMID- 29179563
TI  - Clinical Outcomes for Cystinuria Patients with Unilateral Versus Bilateral
      Cystine Stone Disease.
AB  - INTRODUCTION: Cystinuria is a genetic disorder marked by elevated urinary cystine
      excretion and recurrent cystine nephrolithiasis. Interestingly, despite seemingly
      similar contralateral renal anatomy, a subset of cystinuric patients consistently
      form stones in only one kidney. The aim of this study is to evaluate clinical
      outcomes in unilateral vs bilateral cystine stone formers. PATIENTS AND METHODS:
      We performed a retrospective case-control study of cystinuric patients evaluated
      and treated at the University of California, San Francisco between 1994 and 2015
      and categorized patients as either unilateral or bilateral stone formers.
      Clinical presentation, baseline patient demographics, stone procedures, medical
      therapy regimens, and long-term renal function were compared between the two
      groups. RESULTS: A total of 42 cystine stone patients (22 female, 20 male) were
      included in the analysis. The median age at first presentation was 18.5 years and
      median age at study conclusion was 45.5 years. Two-thirds of patients (n = 28)
      had a history of bilateral stones, whereas one-third (n = 14) had unilateral
      stones. Medical therapy regimens were similar between groups. Despite an
      increased average number of lifetime surgeries (7.5 sessions for bilateral vs 3.7
      sessions for unilateral, p < 0.05), there was no significant difference in
      medians of the most recent glomerular filtration rate when compared with
      unilateral stone formers (81.5 vs 95 mL/min, respectively; p = 0.28).
      CONCLUSIONS: The majority of cystinuric patients within our cohort form stones
      bilaterally during their lifetime, and require more surgical interventions than
      unilateral stone formers. Despite this, overall renal function is well preserved
      in unilateral and bilateral cystinuric stone formers treated with minimally
      invasive stone extraction procedures.

PMID- 29179564
TI  - Chemical components of Hyssopus seravshanicus: antioxidant activity, activations
      of melanogenesis and tyrosinase, and quantitative determination by UPLC-DAD.
AB  - Hyssopus seravshanicus (Dubj.) Pazij has been used as traditional herb and food
      due to its wide biological properties. Seventeen known compounds were isolated
      from the ethyl acetate fraction. Their structures were identified by
      spectroscopic data and comparison with published data. Among them, 14 ones were
      identified from H. seravshanicus for the first time. DPPH and ABTS radical
      scavenging activities for crude ethanol extract (CEE), ethyl acetate fraction
      (EAF), butanol fraction (BF) and compounds 1, 3, 8, 10, 11 and 13 were performed.
      CEE, compounds 1, 3, 11 and 13 exhibited potent antioxidant activities. Compound
      1 was found to increase the melanin content and tyrosinase activity of B16
      melanoma cells. Moreover, the quantitative estimation of compound 1 in the ethyl
      acetate fraction was carried out by UPLC-DAD and the method was validated. This
      is the first report on the isolation and bioactivity research on the non-valotile
      components of H. seravshanicus.

PMID- 29179565
TI  - American Urological Association Antibiotic Best Practice Statement and
      Ureteroscopy: Does Antibiotic Stewardship Help?
AB  - PURPOSE: To determine compliance with the American Urological Association (AUA)
      antimicrobial prophylaxis best practice statement and whether the use of
      postoperative antibiotics is associated with lower rates of postoperative urinary
      tract infection (UTI) in patients with nephroureterolithiasis and a negative
      preoperative urine culture undergoing ureteroscopy. MATERIALS AND METHODS: A
      retrospective review of all adult patients undergoing ureteroscopy from 2013 to
      2014 for stone disease with a negative preoperative urine was conducted. Patients
      who did and did not receive postoperative oral antibiotics beyond 24 hours of
      surgery were identified. The rates of culture-proven postoperative UTI and
      unplanned postoperative encounters were determined for both groups. Between-group
      comparisons were made by using independent t-test and Chi-square analyses.
      RESULTS: A total of 1068 patients met inclusion criteria and 31.6% were managed
      in accordance with the AUA best practice statement by not receiving antibiotics
      beyond 24 hours of surgery. Overall, 33 patients developed a culture-proven UTI
      within 30 days after surgery, with no difference in UTI rate between patients who
      did and did not receive home-going antibiotics (2.9% vs 3.6%, respectively; p =
      0.5). Rates of unplanned hospital encounters also did not differ between groups
      (23.7% vs 27.0%, respectively; p = 0.2). On multivariate regression, culture
      proven UTI within 1 year before surgery was the only factor associated with
      postoperative UTI (odds ratio: 10.8, p < 0.0001). CONCLUSIONS: Patients who did
      and did not receive home-going antibiotics after ureteroscopy demonstrated
      similar rates of postoperative UTI and unplanned hospital encounters. These
      results suggest that there is no benefit to extended antibiotics after
      ureteroscopy. The minority of patients managed in accordance with the AUA best
      practice statement highlights room for quality improvement.

PMID- 29179567
TI  - Number and Frequency of Routinely Applied Painful Procedures in University
      Neonatal Intensive Care Unit.
AB  - Neonates at the neonatal intensive care unit (NICU) are at high risk for
      procedural pain exposure. This study describes the type and frequency of
      procedures in neonates admitted to University Intensive Care Unit. This was a
      prospective cohort study of 150 neonates admitted to the NICU during the first 7
      days of life at a governmental hospital. The type and frequency of procedures
      were evaluated using a tool which included the type and number of procedures
      performed per shift. A total of 14,008 painful procedures were performed on
      neonates with an average of 97.11 painful procedures per baby and 13.9/day for
      each baby. Adhesive removal (21.3%) was the most frequently performed procedure.
      The number of painful procedures was inversely correlated with gestation age ( p
      < .001) and birth weight ( p < .001). The number of painful procedures performed
      on neonates is high, particularly for neonates with small gestational age and low
      birth weight babies.

PMID- 29179566
TI  - The safety assessment of herbals with a new and ethical approach.
AB  - The increasing use of plant medicines (herbals) in Europe needs a shared
      methodology to determine the toxicity and the daily exposure level to these
      drugs. For this reason, the European regulatory agencies have undertaken a study
      that could meet popular uses and toxicological research in different countries of
      the Union. Here we list some examples of the most used herbal drug classes and we
      propose a decision-making process based on their characteristics, their content
      in active principles and on the basis of the present scientific pharmacological
      and toxicological literature. The proposed decision tree actually makes easier
      for the assessor to quickly and accurately evaluate the accredited indexes for
      risk and toxicity assessment based on the preclinical literature data and using
      the correct classification that some of them may have because they are already
      present in medicinal products or used as food.

PMID- 29179568
TI  - Atherogenic Lipoprotein Subfractions and Carotid Atherosclerosis in Menopausal
      Women.
AB  - The aim of the study was to evaluate the relationship between cholesterol
      contained in very-low-density lipoproteins (VLDL-C), intermediate-density
      lipoproteins (IDL-C), low-density lipoproteins, high-density lipoproteins, and
      carotid intima-media thickness (cIMT) and carotid plaques in 228 postmenopausal
      women (63.1 +/- 8.2 years) who participated in the ATENA Project and underwent
      clinical, biochemical (including the assay of lipoproteins using the Lipoprint
      system), and carotid ultrasound tests. Very-low-density lipoprotein cholesterol
      had a statistically significant linear association with cIMT ( P < .001), which
      remained significant after adjustment for age, smoking, systolic blood pressure,
      glucose, and body mass index ( r2 = .20, P < .05). Higher concentrations of IDL-C
      and cholesterol contained in triglyceride-rich lipoproteins (TRL-C, ie, VLDL-C +
      IDL-C) were associated with plaques in the common carotid (tertile III/tertile I:
      odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.21-5.32, P < .02; OR =
      2.30, 95% CI = 1.05-5.01, P < .05, respectively), after adjustment for main
      cardiovascular risk factors. In conclusion, high concentrations of VLDL-C and TRL
      C are independently associated with the presence of carotid plaques. Their assay
      represents a useful tool for improving our knowledge on the role of different
      classes of lipoproteins in atherosclerosis.

PMID- 29179569
TI  - Self-Injurious Behavior in Children With Developmental Disabilities: A Systematic
      Review of Behavioral Intervention Literature.
AB  - We reviewed single-case research studies examining the effects of behavioral
      interventions for self-injurious behavior (SIB) in young children with autism and
      developmental disabilities. Systematic searches of electronic databases,
      journals, and reference lists identified 46 studies (66 participants younger than
      the age of 12) meeting inclusion criteria. Studies were examined based on (a)
      participant demographics, (b) topography and function of SIB, (c) type of
      functional behavior assessment (FBA), (d) intervention procedures and outcomes,
      and (e) experimental design and measurement. Intervention strategies were
      categorized as antecedent manipulations, teaching behavior, consequence-based
      procedures, and/or extinction procedures. Positive outcomes were reported for 78%
      of participants in the reviewed studies and 88% of the participants were
      diagnosed with autism. Results suggest the effectiveness of behavioral
      interventions to decrease SIB for young children with disabilities; however, the
      frequent use of packaged interventions without component analysis limits the
      conclusiveness of any treatment recommendation. Suggestions for future research
      are discussed.

PMID- 29179570
TI  - A narrow view: The conceptualization of sexual problems in human sexuality
      textbooks.
AB  - This study examined the ways in which the meaning of 'sexual problems' is
      constructed and defined in undergraduate human sexuality textbooks. Drawing on
      feminist and critical discourse frameworks, the dominant as well as the
      absent/marginalized discourses were identified using critical discourse analysis.
      Sexual difficulties were largely framed by the American Psychiatric Association's
      Diagnostic and Statistical Manual of Mental Disorders. Thus, medical discourse
      was privileged. Alternative conceptualizations and frameworks, such as the New
      View of Women's Sexual Problems, were included marginally and peripherally. We
      argue that current constructions of sexuality knowledge reinforce, rather than
      challenge, existing hegemonic discourses of sexuality.

PMID- 29179571
TI  - Role of Basal Cells in Producing Persistent Lentivirus-Mediated Airway Gene
      Expression.
AB  - Cystic fibrosis (CF) lung disease is an ideal candidate for a genetic therapy. It
      has been shown previously that preconditioning with lysophosphatidylcholine (LPC)
      prior to lentiviral (LV) vector delivery results in long-term in vivo gene
      expression in the airway epithelium of CF mice. It was hypothesized that this
      outcome is largely due to transduction of airway basal cells that in turn pass
      the transgene onto their progeny. The aim of these studies was to confirm if the
      in vivo delivery of a human immunodeficiency virus type 1 (HIV-1) vesicular
      stomatitis virus envelope glycoprotein (VSV-G) pseudotyped LV vector following
      LPC airway conditioning results in transduction of mouse airway basal cells in
      situ and if the transgene is passed onto their progeny. Additionally, the study
      sought to determine the efficiency of in vitro transduction of human airway basal
      cells. First, normal mouse nasal airways were pretreated with LPC prior to
      delivery of a HIV-1 VSV-G pseudotyped LV vector carrying a LacZ marker gene (LV
      LacZ). An epithelial ablation model utilizing polidocanol was then used to
      demonstrate that clonal outgrowth of linear and spotted clusters of transgene
      expressing ciliated, basal, and goblet cells occurs following transduction of
      basal cells. Second, human basal cells were cultured from primary bronchial
      epithelial cells, with identity confirmed by keratin 5 staining. High levels of
      transgene expression were found following LV-LacZ transduction. This study
      demonstrates the ability of the vector delivery protocol to transduce mouse
      airway basal cells, the LV vector to transduce human basal cells, and the likely
      role of these cells in maintaining long-term gene expression. These findings
      support and further develop the potential of LV gene transfer for persistent
      correction of CF airway disease.

PMID- 29179573
TI  - The Value of Rehabilitation Medicine for Patients Receiving Palliative Care.
AB  - BACKGROUND: Rehabilitation medicine is a multidisciplinary field aimed at
      improving patients' quality of life by improving function. Patients receiving
      palliative care frequently share common symptoms including fatigue, decreased
      functional independence, mood disorders, pain, and breathlessness. Many
      rehabilitation interventions can improve these symptoms. OBJECTIVE: To evaluate
      the scope and effectiveness of rehabilitation interventions and exercise programs
      in improving quality of life and distressing symptoms in patients receiving
      palliative care. METHODS: We conducted a literature review of cancer
      rehabilitation topics and techniques specifically applied to patients with life
      limiting conditions. Exercise and other rehabilitation interventions were
      analyzed for their effects on common symptoms and disabilities experienced by
      this patient population. CONCLUSION: Current available literature supports the
      use of exercise programs and rehabilitation interventions to improve fatigue,
      mood, functional independence, breathlessness, and pain. Rehabilitation and
      palliative care practitioners share many goals in their approach to patient care
      and augment one another well. Palliative care providers should consider referral
      to physiatry (physical medicine and rehabilitation) to help optimize patients'
      quality of life.

PMID- 29179572
TI  - When and Why Do Neonatal and Pediatric Critical Care Physicians Consult
      Palliative Care?
AB  - BACKGROUND: Parents of children admitted to neonatal and pediatric intensive care
      units (ICUs) are at increased risk of experiencing acute and post-traumatic
      stress disorder. The integration of palliative care may improve child and family
      outcomes, yet there remains a lack of information about indicators for specialty
      level palliative care involvement in this setting. OBJECTIVE: To describe
      neonatal and pediatric critical care physician perspectives on indicators for
      when and why to involve palliative care consultants. METHODS: Semistructured
      interviews were conducted with 22 attending physicians from neonatal, pediatric,
      and cardiothoracic ICUs in a single quaternary care pediatric hospital.
      Transcribed interviews were analyzed using content and thematic analyses.
      RESULTS: We identified 2 themes related to the indicators for involving
      palliative care consultants: (1) palliative care expertise including support and
      bridging communication and (2) organizational factors influencing communication
      including competing priorities and fragmentation of care. CONCLUSIONS: Palliative
      care was most beneficial for families at risk of experiencing communication
      problems that resulted from organizational factors, including those with long
      lengths of stay and medical complexity. The ability of palliative care
      consultants to bridge communication was limited by some of these same
      organizational factors. Physicians valued the involvement of palliative care
      consultants when they improved efficiency and promoted harmony. Given the
      increasing number of children with complex chronic conditions, it is important to
      support the capacity of ICU clinical teams to provide primary palliative care. We
      suggest comprehensive system changes and critical care physician training to
      include topics related to chronic illness and disability.

PMID- 29179575
TI  - Acknowledgments to AOP Peer Reviewers November 1, 2016, to November 1, 2017.

PMID- 29179574
TI  - Life-Sustaining Treatment Status at the Time of Death in a Japanese Pediatric
      Intensive Care Unit.
AB  - BACKGROUND: Substantial variability exists among countries regarding the modes of
      death in pediatric intensive care units (PICUs). However, there is limited
      information on end-of-life care in Japanese PICUs. Thus, this study aimed to
      elucidate the characteristics of end-of-life care practice for children in a
      Japanese PICU. METHODS: We examined life-sustaining treatment (LST) status at the
      time of death based on medical chart reviews from 2010 to 2014. All deaths were
      classified into 3 groups: limitation of LST (limitation group, death after
      withholding or withdrawal of LST or a do not attempt resuscitation order), no
      limitation of LST (no-limitation group, death following failed resuscitation
      attempts), or brain death (brain death group). RESULTS: Of the 62 patients who
      died, 44 (71%) had limitation of LST, 18 (29%) had no limitation of LST, and none
      had brain death. In the limitation group, the length of PICU stay was longer than
      that in the no-limitation group (13.5 vs 2.5 days; P = .01). The median time to
      death after the decision to limit LST was 2 days (interquartile range: 1-5.5
      days), and 94% of the patients were on mechanical ventilation at the time of
      death in the limitation group. CONCLUSIONS: Although limiting LST was a common
      practice in end-of-life care in a Japanese PICU, a severe limitation of LST such
      as withdrawal from the ventilator was hardly practiced, and a considerable LST
      was still provided at the time of death.

PMID- 29179576
TI  - Rates and Predictors of Conversion to Schizophrenia or Bipolar Disorder Following
      Substance-Induced Psychosis.
AB  - OBJECTIVE: The authors investigated the rates of conversion to schizophrenia and
      bipolar disorder after a substance-induced psychosis, as well as risk factors for
      conversion. METHOD: All patient information was extracted from the Danish Civil
      Registration System and the Psychiatric Central Research Register. The study
      population included all persons who received a diagnosis of substance-induced
      psychosis between 1994 and 2014 (N=6,788); patients were followed until first
      occurrence of schizophrenia or bipolar disorder or until death, emigration, or
      August 2014. The Kaplan-Meier method was used to obtain cumulative probabilities
      for the conversion from a substance-induced psychosis to schizophrenia or bipolar
      disorder. Cox proportional hazards regression models were used to calculate
      hazard ratios for all covariates. RESULTS: Overall, 32.2% (95% CI=29.7-34.9) of
      patients with a substance-induced psychosis converted to either bipolar or
      schizophrenia-spectrum disorders. The highest conversion rate was found for
      cannabis-induced psychosis, with 47.4% (95% CI=42.7-52.3) converting to either
      schizophrenia or bipolar disorder. Young age was associated with a higher risk of
      converting to schizophrenia. Self-harm after a substance-induced psychosis was
      significantly linked to a higher risk of converting to both schizophrenia and
      bipolar disorder. Half the cases of conversion to schizophrenia occurred within
      3.1 years after a substance-induced psychosis, and half the cases of conversion
      to bipolar disorder occurred within 4.4 years. CONCLUSIONS: Substance-induced
      psychosis is strongly associated with the development of severe mental illness,
      and a long follow-up period is needed to identify the majority of cases.

PMID- 29179577
TI  - Service Use Preceding Opioid-Related Fatality.
AB  - OBJECTIVE: This study analyzed health service patterns before opioid-related
      death among nonelderly individuals in the Medicaid program, focusing on decedents
      with and without past-year diagnoses of noncancer chronic pain. METHODS: The
      authors identified opioid-related decedents, age <=64 years, in the Medicaid
      program and characterized their clinical diagnoses, filled medication
      prescriptions, and nonfatal poisoning events during the 30 days and 12 months
      before death. The study group included 13,089 opioid-related deaths partitioned
      by presence or absence of chronic noncancer pain diagnoses in the last year of
      life. RESULTS: Most decedents (61.5%) had received clinical diagnoses of chronic
      noncancer pain conditions in the last year of life. As compared with decedents
      without chronic pain diagnoses, those with these diagnoses were significantly
      more likely to have filled prescriptions for opioids (49.0% versus 17.2%) and
      benzodiazepines (52.1% versus 26.6%) during the last 30 days of life, while
      diagnoses of opioid use disorder during this period were uncommon in both groups
      (4.2% versus 4.3%). The chronic pain group was also significantly more likely
      than the nonpain group to receive clinical diagnoses of drug use (40.8% versus
      22.1%), depression (29.6% versus 13.0%) or anxiety (25.8% versus 8.4%) disorders
      during the last year of life. CONCLUSIONS: Persons dying of opioid-related
      causes, particularly those who were diagnosed with chronic pain conditions,
      commonly received services related to drug use disorders and mental disorders in
      the last year of life, though opioid use disorder diagnoses near the time of
      death were rare.

PMID- 29179578
TI  - Impact of SSRI Therapy on Risk of Conversion From Mild Cognitive Impairment to
      Alzheimer's Dementia in Individuals With Previous Depression.
AB  - OBJECTIVE: Depression is associated with an increased risk of Alzheimer's
      disease. Research has shown that the selective serotonin reuptake inhibitor
      (SSRI) citalopram decreases amyloid-beta generation and plaque load. The authors
      evaluated the impact of SSRI treatment on CSF biomarkers and progression from
      mild cognitive impairment (MCI) to Alzheimer's dementia. METHOD: Data sets from
      755 currently nondepressed participants from the longitudinal Alzheimer's Disease
      Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of
      variance and covariance with ApoE4 status and age as covariates. RESULTS: In MCI
      patients with a history of depression, long-term SSRI treatment (>4 years) was
      significantly associated with a delayed progression to Alzheimer's dementia by
      approximately 3 years, compared with short-term SSRI treatment, treatment with
      other antidepressants, or no treatment and compared with MCI patients without a
      history of depression. No differences in CSF biomarker levels were observed
      between treatment groups. CONCLUSIONS: Long-term SSRI treatment may delay
      progression from MCI to Alzheimer's dementia.

PMID- 29179579
TI  - A Population-Based Longitudinal Study of Symptoms and Signs Before the Onset of
      Psychosis.
AB  - OBJECTIVE: The authors sought to characterize the symptoms of patients later
      hospitalized for psychotic disorders in primary mental health outpatient
      settings, and to investigate whether these symptoms can be used to predict later
      onset of psychotic illness. METHOD: This was a population-based historical
      prospective cohort study using national registers of clinical psychiatric
      services. The sample (N=114,983) comprised 18- to 21-year-olds serving in the
      Israeli military and examined in military mental health outpatient clinics across
      72 consecutive months. RESULTS: Overall, 1,092 individuals (0.95%) not diagnosed
      with a psychotic disorder at the time of examination were hospitalized for
      nonaffective psychotic disorder up to 9 years after the index examination. A
      principal components analysis of symptoms presented at index examination found
      that a symptom cluster of thought disorder, perceptual abnormalities, poor
      orientation, and suicidality was associated with an increased risk for
      hospitalization for nonaffective psychotic disorder within 14 days after
      examination (hazard ratio=45.80, 95% CI=22.87-91.73), 15-111 days after
      examination, (hazard ratio=19.59, 95% CI=13.08-29.33), 112-365 days after
      examination (hazard ratio=4.94, 95% CI=2.59-9.40), and 1-3.5 years after
      examination (hazard ratio=3.42, 95% CI=2.21-5.28), but not for hospitalization
      3.5 years or more after examination (hazard ratio=1.57, 95% CI=0.91-2.71).
      Despite the increased risk, the positive predictive values of this symptom
      cluster were low, ranging from 0.54% to 1.99%. CONCLUSIONS: In 18- to 21-year
      olds, the presence of psychotic symptoms was associated with later
      hospitalization for a nonaffective psychotic disorder. However, the low positive
      predictive values of symptoms elicited in primary mental health care settings
      suggest that symptoms alone are not useful in predicting later hospitalization
      for nonaffective psychotic disorder.

PMID- 29179580
TI  - Association of FV G1691A Polymorphism but not A4070G With Coronary Artery
      Disease.
AB  - Coronary artery disease (CAD) is one of the chief causes of death in the world.
      Several hypotheses have been promoted as for the origin of the disease, among
      which are genetic predispositions and/or environmental factors. The aim of this
      study was to determine the effect of factor V (FV) gene polymorphisms (Leiden,
      G1691A [FVL] and HR2 A4070G) and to analyze their association with traditional
      risk factors in assessing the risk of CAD. Our study population included 200
      Tunisian patients with symptomatic CAD and a control group of 300 participants
      matched for age and sex. All participants were genotyped for the FVL and HR2
      polymorphisms. Multivariate logistic regression was applied to analyze
      independent factors associated with the risk of CAD. Our analysis showed that the
      FVL A allele frequency ( P < 10-3, odds ratio [OR] = 2.81, 95% confidence
      interval [CI] = 1.6-4.9) and GA genotype ( P < 10-3, OR = 4.03, 95% CI = 2.1-7.6)
      are significantly more prevalent among patients with CAD compared to those
      controls and may be predisposing to CAD. We further found that the FVL mutation
      is an independent risk factor whose effect is not modified by other factors
      (smoking, diabetes, hypertension, dyslipidemia, and a family history of CAD) in
      increasing the risk of the disease. However, analysis of FV HR2 variation does
      not show any statistically significant association with CAD. The FVL polymorphism
      may be an independent risk factor for CAD. However, further investigations on
      these polymorphisms and their possible synergisms with traditional risk factors
      for CAD could help to ascertain better predictability for CAD susceptibility.

PMID- 29179581
TI  - Hadza Men With Lower Voice Pitch Have a Better Hunting Reputation.
AB  - Previous research with hunter-gatherers has found that women perceive men with
      voices manipulated to be lower in pitch to be better hunters, and men perceive
      women with lower pitch to be better gatherers. Here, we test if actual voice
      pitch is associated with hunting and gathering reputations in men and women,
      respectively. We find that voice pitch does relate to foraging reputation in men,
      but not in women, with better hunters having a lower voice pitch. In addition, we
      find that the previously documented relationship between voice pitch and
      reproductive success no longer holds when controlling for hunting reputation, but
      hunting reputation remains a significant predictor of reproductive success when
      controlling for voice pitch. This raises the possibility that voice pitch is
      being selected for in hunter-gatherers because of the relationship between voice
      pitch and hunting reputation.

PMID- 29179582
TI  - Is Support of Censoring Controversial Media Content for the Good of Others?
      Sexual Strategies and Support of Censoring Pro-Alcohol Advertising.
AB  - At least in the United States, there are widespread concerns with advertising
      that encourages alcohol consumption, and previous research explains those
      concerns as aiming to protect others from the harm of excessive alcohol use.1
      Drawing on sexual strategies theory, we hypothesized that support of censoring
      pro-alcohol advertising is ultimately self-benefiting regardless of its
      altruistic effect at a proximate level. Excessive drinking positively correlates
      with having casual sex, and casual sex threatens monogamy, one of the major means
      with which people adopting a long-term sexual strategy increase their inclusive
      fitness. Then, one way for long-term strategists to protect monogamy, and thus
      their reproductive interest is to support censoring pro-alcohol advertising,
      thereby preventing others from becoming excessive drinkers (and consequently
      having casual sex) under media influence. Supporting this hypothesis, three
      studies consistently showed that restricted sociosexuality positively correlated
      with support of censoring pro-alcohol advertising before and after various value
      , ideological-, and moral-foundation variables were controlled for. Also as
      predicted, Study 3 revealed a significant indirect effect of sociosexuality on
      censorship support through perceived media influence on others but not through
      perceived media influence on self. These findings further supported a self
      interest analysis of issue opinions, extended third-person-effect research on
      support of censoring pro-alcohol advertising, and suggested a novel approach to
      analyzing media censorship support.

PMID- 29179583
TI  - Oncolytic Viruses for Tumor Precision Imaging and Radiotherapy.
AB  - In 2003 in China, Peng et al. invented the recombinant adenovirus expressing p53
      (Gendicine) for clinical tumor virotherapy. This was the first clinically
      approved gene therapy and tumor virotherapy drug in the world. An oncolytic
      herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor
      (Talimogene laherparepvec) was approved for melanoma treatment in the United
      States in 2015. Since then, oncolytic viruses have been attracting more and more
      attention in the field of oncology, and may become novel significant modalities
      of tumor precision imaging and radiotherapy after further improvement. Oncolytic
      viruses carrying reporter genes can replicate and express genes of interest
      selectively in tumor cells, thus improving in vivo noninvasive precision
      molecular imaging and radiotherapy. Here, the latest developments and molecular
      mechanisms of tumor imaging and radiotherapy using oncolytic viruses are
      reviewed, and perspectives are given for further research. Various types of
      tumors are discussed, and special attention is paid to gastrointestinal tumors.

PMID- 29179584
TI  - Maternal height and risk of hypertensive disorders in pregnancy.
AB  - PURPOSE: The relationship between maternal height and gestational hypertensive
      disorders was examined in a cohort of Chinese gravidae managed in 1997-2013 to
      clarify the association between short stature with preeclampsia (PE) and
      gestational hypertension (GH). MATERIALS AND METHODS: Retrospective study of 87
      290 gravidae categorized by their height into four quartile groups. The impact of
      short stature, defined as height in the lowest quartile, on incidence of PE and
      GH was studied in relation to the presence of risk factors. The independent role
      of short stature was determined by regression analysis. RESULTS: The 25th, 50th,
      and 75th percentile values of height were 154 cm, 158 cm, and 161 cm
      respectively. The incidence of PE, but not GH, was inversely correlated with
      height (p = .025). Short stature altered the impact of parity status, advanced
      age, high body mass index, infant gender, and medical history, on incidence of PE
      but not GH. On regression analysis, short stature increased risk of PE (adjusted
      RR 1.134, 95%CI 1.005-1.279) but reduced GH (adjusted RR 0.836, 95%CI 0.718
      0.974). CONCLUSIONS: Maternal short stature should be defined according to
      distribution in a specific ethnic group, and it exerts a significant but opposite
      effect on the incidence of PE versus GH.

PMID- 29179586
TI  - Challenges in oscillometric blood pressure measurement in atrial fibrillation:
      looking for practical solutions.

PMID- 29179588
TI  - Listeriosis in two twin pregnancies after in vitro fertilization with
      differential outcome and literature review.
AB  - PURPOSE: In vitro fertilization (IVF) has become a very common procedure in the
      infertility practice due to its accessibility. The study is aiming at presenting
      two twin pregnancy-related infections caused by Listeria monocytogenes and
      reviewing the reported cases of listeriosis in multiple pregnancies. MATERIALS
      AND METHODS: Two listeriosis cases with twin pregnancy after IVF were described
      and the literature on pregnancy-associated listeriosis was reviewed. RESULTS: The
      risk of listeriosis should be underscored in pregnant women after IVF, and timely
      diagnosis and rational treatment might result in a better outcome. CONCLUSIONS:
      The current study highlights that the infections due to L. monocytogenes should
      be noted in multiple pregnancies after IVF.

PMID- 29179587
TI  - In vitro differentiation of progenitor cells isolated from juvenile pig hearts -
      expression of relevant gene and protein markers.
AB  - OBJECTIVES: Heart failure is a significant cause of mortality worldwide, and most
      current therapies treat only its symptoms. The results of cardiac stem cell
      research suggest a promising treatment option for heart failure, but there is
      currently an unmet demand for better research models. We have therefore, for the
      first time, isolated, expanded and differentiated progenitor cells obtained from
      juvenile pig hearts to use as a platform for cardiac stem cell research. DESIGN:
      Progenitor cells were isolated from the left ventricles of porcine hearts using
      collagenase enzymatic digestion and Percoll(r)-gradient centrifugation. Cells
      were proliferated in Matrigel(r)-coated wells. Cell differentiation was initiated
      by applying 5-azacytidine and subsequently controlled by modifying the serum
      concentration. Western blotting and qPCR were used to determine protein and gene
      expression, respectively. RESULTS: Cardiac-specific genes, from the following
      proteins: troponin I-3, and myosin-heavy-chain 7 were stably expressed during
      proliferation and differentiation. Connexin-43 was upregulated and Actinin alfa 2
      was downregulated during differentiation. The immature-cardiomyocyte marker GATA
      binding protein 4 was stably expressed but with a decrease in expression at day 4
      of differentiation. Smooth muscle actin decreased in expression and Von
      Willebrand factor were stably expressed during differentiation. Smooth muscle
      protein expression was documented but no expression of cardiac-specific proteins
      after differentiation was found. CONCLUSION: The isolated progenitor cells had
      key cardiac-lineage gene expression characteristics but they did not express
      cardiac-specific proteins. Smooth muscle protein was expressed confirming
      commitment to the smooth muscle lineage.

PMID- 29179585
TI  - Immune-based strategies for mood disorders: facts and challenges.
AB  - INTRODUCTION: Inflammation seems to play a role in the pathophysiology of mood
      disorders, including major depressive disorder (MDD) and bipolar disorder (BD).
      In the last years several studies have shown increased levels of inflammatory
      and/or immune markers in patients with mood disorders. Accordingly, the immune
      system has become a target of interest for the development of biomarkers and
      therapeutics for mood disorders. Areas covered: Here, we review the evidence
      showing low-grade inflammation in mood disorders and the studies evaluating
      immune-based strategies for the treatment of these conditions. Expert commentary:
      Clinical trials with non-steroidal anti-inflammatory drugs, polyunsaturated
      acids, N-acetylcysteine, anti-cytokines, physical activity and probiotics have
      provided promising results in terms of antidepressant efficacy in patients with
      MDD and BD. Regarding stem cells, only studies with animal models have been
      performed so far with interesting pre-clinical results. Due to the preliminary
      nature of the results, most of the clinical studies need to be replicated and/or
      confirmed in larger clinical settings, embracing the highly heterogeneous
      pathophysiology of mood disorders.

PMID- 29179589
TI  - Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in
      women with antiphospholipid antibody syndrome: a meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: This study was designed to evaluate the efficacy of aspirin or heparin
      or both in the treatment for recurrent spontaneous abortion (RSA) in women with
      antiphospholipid antibody syndrome (APS). METHODS: Systematic searches for
      randomized clinical trials (RCTs) evaluating on live birth and preterm delivery,
      preeclampsia, intrauterine growth restriction, gestational diabetes, bleeding of
      RSA with APS patients receiving aspirin, and heparin therapy were carried out,
      from PubMed, EMBASE, ScienceDirect, and CNKI. Related data were extracted from
      eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Relative
      risk (RR) and its 95% confidence interval were calculated. RESULTS: Nineteen
      publications with randomized controlled trials were selected for this study,
      which included a total of 1251 pregnant patients with diagnosis of RSA with APS.
      With respect to live birth, it was remarkably improved in aspirin plus heparin or
      heparin alone group [RR =1.23, 95% CI (1.12-1.36), p < .0001; RR = 1.18, 95% CI
      (1.03-1.35), p = .02]; aspirin alone group, however, there was no statistically
      significant difference compare to placebo [RR = 0.97, 95% CI (0.80-1.16), p =
      .71]. Meanwhile, aspirin plus heparin therapy did not significantly reduce the
      risk of recurrent placenta-mediated pregnancy complications including preterm
      birth, intrauterine growth retardation (IUGR), gestational diabetes, and minor
      bleeding. A beneficial therapeutic effect of heparin alone therapy was found on
      preventing preterm birth and low-dose aspirin plus heparin therapy was
      significant reduce the risk of preeclampsia. CONCLUSION: An improvement of
      pregnancy outcomes in women with RSA and APS can be achieved by treatment
      strategies combining low-dose aspirin plus heparin or heparin alone. Aspirin
      alone, by contrast, seemed inferior to other treatments in achieving more live
      birth.

PMID- 29179590
TI  - Induction of apoptosis by metformin and progesterone in estrogen-induced
      endometrial hyperplasia in rats: involvement of the bcl-2 family proteins.
AB  - This study compared the antiproliferative effects of metformin and progesterone,
      via examination of the Bcl-2/Bax-caspase apoptotic pathway in estrogen-induced
      endometrial hyperplasia (EH) in 40 rats. Two rats died after bilateral
      oophorectomy, and 1 week after surgery, the remaining 38 were randomly divided
      into three groups: the first (control, n = 12) received 4 mg/kg 17beta estradiol
      hemihydrate (E); the second (n = 13) received 4 mg/kg 17beta estradiol
      hemihydrate and 50 mg/kg metformin (E + M); and the third (n = 13) received 4
      mg/kg 17beta estradiol hemihydrate and 1 mg/day medroxiprogesterone acetate (E +
      MPA). Histological markers and Bcl-2, Bax and caspase 9 expression were analyzed.
      Luminal epithelial thickness, density of gland and epithelial height was
      significantly higher in group E than in groups E + M and E + MPA. Histopathologic
      parameters were similar between the E + M and E + MPA groups. Bcl-2/Bax ratio was
      significantly decreased in the E + M and E + MPA groups and caspase 9 expression
      levels were significantly increased in the E + M and E + MPA groups, compared
      with the control group. In addition, Bcl-2/Bax ratio and caspase 9 expression
      were similar between the E + M and E + MPA groups. The data indicate that
      metformin reduces estrogen-induced EH in rats, via activation of the caspase
      dependent mitochondrial apoptotic pathway, to the same degree as progesterone.

PMID- 29179591
TI  - Effects of Gly71Arg mutation in UGT1A1 gene on neonatal hyperbilirubinemia: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: The associations between Gly71Arg polymorphism in the coding region of
      uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene and the risk of
      neonatal hyperbilirubinemia remained controversial. Therefore, a meta-analysis of
      observational studies has been conducted to assess the relationship between
      UGT1A1 gene polymorphism of Gly71Arg and neonatal hyperbilirubinemia
      susceptibility. METHODS: An electronic literature search from online databases,
      such as PubMed, Embase, Cochrane, and Scopus was conducted to identify eligible
      studies. The effect summary odds ratio (OR) with 95% confidence interval (CI) was
      used to estimate the strength of association in the fixed or random effects
      model, based on the absence or presence of heterogeneity. RESULTS: A total of 32
      eligible studies involving 2634 cases of neonatal hyperbilirubinemia and 4996
      controls were enrolled in this meta-analysis. The combined results showed that
      UGT1A1 Gly71Arg polymorphism was associated with an increased risk of neonatal
      hyperbilirubinemia in all genetic models (homozygote model: OR = 6.12, 95% CI =
      4.42-8.46; heterozygote model: OR = 2.06, 95% CI = 1.82-2.33; dominant model: OR
      = 2.44, 95% CI = 2.03-2.93; recessive model: OR = 4.79, 95% CI = 3.48-6.59, and
      allelic model: OR = 2.37, 95% CI = 1.98-2.82). Subgroup analysis by ethnicity
      strongly validated this correlation in Asians but slightly in Caucasian
      population. CONCLUSIONS: This meta-analysis confirms that UGT1A1 Gly71Arg
      polymorphism significantly increases the risk of neonatal hyperbilirubinemia in
      Asian population, but results from the Caucasians were conflicting and further
      well-designed epidemiological studies are, therefore, required to more adequately
      assess this correlation.

PMID- 29179592
TI  - Elevated plasma procalcitonin level predicts poor prognosis of ST elevation
      myocardial infarction in Asian elderly.
AB  - Previous studies have focused on relationship between plasma procalcitonin level
      and myocardial infarction risk, but this relationship in Asian elderly has not
      been investigated. The aim of this study was to reveal the association of
      peripheral procalcitonin concentration (both immediate and average levels) with
      myocardial infarction prognosis in Asian elderly. A total of 400 ST-elevation
      myocardial infarction patients, 400 unstable angina patients and 400 controls
      were included. Plasma levels of high-sensitivity C-reactive protein and
      procalcitonin were measured using commercially available kits. Each myocardial
      infarction patient received a standard therapy and a 12-month follow-up unless
      major adverse cardiac events occurred. On admission, plasma procalcitonin level
      was higher in myocardial infarction patients than in unstable angina patients and
      controls (p < .001). In the follow-up period, 142 myocardial infarction patients
      suffered from major adverse cardiac events, and other 258 myocardial infarction
      patients did not. Higher admission, peak and average plasma levels of
      procalcitonin in the first week after chest pain onset were associated with
      elevated risk of major adverse cardiac events (HR: 1.46, 95%CI: 1.18-1.99; HR:
      2.57, 95%CI: 1.99-3.52; HR: 2.36, 95%CI: 1.81-3.00). Plasma procalcitonin level
      had a positive linear correlation with plasma level of high-sensitivity C
      reactive protein on admission (r = 0.650, p < .001). In conclusion, peripheral
      concentration of procalcitonin (both immediate and average levels) might be an
      independent predictor for prognosis in myocardial infarction patients. Prognostic
      significance of procalcitonin might be implicated in inflammation.

PMID- 29179593
TI  - De-novo identification of specific exposure biomarkers of the alternative
      plasticizer di(2-ethylhexyl) terephthalate (DEHTP) after low oral dosage to male
      volunteers by HPLC-Q-Orbitrap-MS.
AB  - CONTEXT: Human exposure biomonitoring relies on the availability of specific,
      sensitive biomarkers. For emerging chemicals, the identification (prediction,
      synthesis, verification) of such biomarkers is time and cost intensive.
      OBJECTIVE: This study aimed to further elucidate the urinary metabolic profile of
      the plasticizer di(2-ethylhexyl) terephthalate (DEHTP) in search of probably
      additional biomarkers of exposure. MATERIALS AND METHODS: Urine samples of an
      oral low-dose volunteer study were analysed by HPLC-Q-Orbitrap-MS combined with a
      commercial data mining software. Metabolite identification was based on isotopic
      pattern, accurate masses of product ions and excretion profiles. RESULTS: Nine
      phase I metabolites of DEHTP were tentatively identified by HPLC-Q-Orbitrap-MS.
      Four previously described, side chain oxidized monoester metabolites were
      confirmed in all samples. In addition, five previously unknown downstream
      metabolites were tentatively identified. DISCUSSION AND CONCLUSION: The excretion
      profiles obtained by HPLC-Q-Orbitrap-MS were in good agreement with quantitative
      HPLC-QqQ-MS data. For the newly discovered metabolites, plausible excretion
      profiles, similar to the ones of the known metabolites, were obtained. The
      presented approach proved to be successful for metabolite screening in urine
      samples after low-dose exposure and will be applied in future human metabolism
      studies for a fast, reliable and cost effective identification of specific
      biomarkers of exposure.

PMID- 29179594
TI  - Ultrabilitation: beyond recovery-oriented rehabilitation.
AB  - PURPOSE: Current rehabilitation models emphasize therapy that attempts to return
      to "normal" the lives of persons who are disabled. An opportunity is available to
      scrutinize whether this recovery orientation of rehabilitation is necessarily
      optimal. METHOD: This conceptual article uses reasoning, informed by experience
      and a nonsystematic review of literature across diverse disciplines. RESULTS: For
      some persons with disability, optimizing recovery might be unwanted or
      insufficient. To expand rehabilitation, we append the Latin "ultra", beyond, to
      "habilitare", make fit. The resulting term, "ultrabilitate", commits to human
      flourishing that moves persons toward, around or beyond recovery of particular
      functioning. CONCLUSIONS: By expanding the scope of disability management,
      ultrabilitation could inform therapy selection and facilitate human flourishing.
      Empirical research is needed to test our ideas. Implications for rehabilitation
      Despite significant progress, rehabilitation limits some people with
      disabilities. Modern health systems still benchmark therapy for rehabilitation
      against "normal" or species-typical standards to aid recovery. "Ultrabilitation",
      meaning "beyond fitness", promotes flourishing, either without an interest in
      recovery or in moving toward, beyond or around recovery. Biological, social and
      technological conditions are needed to support ultrabilitation. Ultrabilitation
      complements rehabilitation when rehabilitation is not sufficient to optimize
      functioning and personal growth.

PMID- 29179595
TI  - Efficacy and safety of aripiprazole lauroxil once-monthly versus aripiprazole
      once-monthly long-acting injectable formulations in patients with acute symptoms
      of schizophrenia: an indirect comparison of two double-blind placebo-controlled
      studies.
AB  - BACKGROUND: Aripiprazole lauroxil (AL) is a long-acting injectable atypical
      antipsychotic recently approved for the treatment of schizophrenia. OBJECTIVE: To
      indirectly compare the safety and efficacy of AL and aripiprazole once-monthly
      (AOM). METHODS: A systematic search was performed to identify randomized,
      controlled trials of AOM and AL that met criteria for indirect comparison
      according to Bayesian network meta-analysis. The analysis indirectly compared AL
      and AOM treatment groups for efficacy by mean change in Positive and Negative
      Syndrome Scale (PANSS) total score and >=30% reduction in PANSS total score, as
      well as tolerability including adverse events, akathisia, and weight gain.
      RESULTS: Two studies were selected, resulting in three active-treatment groups:
      AL 441 mg, AL 882 mg, and AOM 400 mg. All active treatments were efficacious
      compared with placebo. There were no differences in indirect comparisons of
      akathisia. All three groups showed some weight gain, but only the AOM 400 mg
      group was significantly greater than placebo. CONCLUSIONS: Results of this
      indirect comparison found that both doses of AL and the single AOM dose were
      therapeutic and efficacious for the treatment of schizophrenia with a similar
      safety profile.

PMID- 29179596
TI  - Celastrol attenuates impairments associated with lipopolysaccharide-induced acute
      respiratory distress syndrome (ARDS) in rats.
AB  - Celastrol, a constituent from a traditional Chinese medicinal herb belonging to
      the family Celastraceae, has been shown to impart anti-inflammatory properties,
      in part, by inhibiting NF-kappaB activity and related induction of pro
      inflammatory cytokine formation/release. The present study investigated the
      effects of celastrol in an animal model of acute respiratory distress syndrome
      (ARDS) induced by intratracheal administration of lipopolysaccharides (LPSs).
      Celastrol pre-treatment groups received celastrol by intraperitoneal injection on
      seven consecutive days before LPS treatment. In rats evaluated 24 h after LPS
      administration, oxygenation indices and lung injury were measured, as were levels
      of inflammatory cells and cytokines in isolated bronchoalveolar lavage fluid
      (BALF). Lung tissue expression of proteins involved in NF-kappaB and ERK/MAPK
      pathways were measured by Western blot analyses. Celastrol pre-treatments
      appeared to attenuate LPS-induced lung injury and inflammatory responses in the
      rats, including decreases in inducible aggregation?infiltration of inflammatory
      cells and production/release of pro-inflammatory cytokines into the lung airways.
      Celastrol appeared to also inhibit NF-kappaB activation, but had no effect on
      ERK/MAPK pathways in the LPS-induced ARDS. The results here thus indicated that
      celastrol pre-treatment could impart protective effects against LPS-induced ARDS,
      and that these effects may be occurring through an inhibition of induction of NF
      kappaB signaling pathways.

PMID- 29179597
TI  - Spontaneous extradural hematoma: a rare entity.
AB  - Spontaneous onset extradural hematoma (EDH) is a very rare entity and has been
      seen mostly to be associated with adjacent infective pathologies, dural vascular
      malformations, extradural metastasis, or coagulopathies. We report a series of
      two such cases and review the literature. One case presented with spontaneous EDH
      that was managed conservatively and was diagnosed to have chronic kidney disease
      later; the other had deranged coagulation profile and liver function secondary to
      drug induced hepatitis and was operated. Both patients were discharged in a
      stable condition and were improving on follow up.

PMID- 29179598
TI  - Serum paracetamol-protein adducts in ambulatory subjects: Relationship to recent
      reported paracetamol use.
AB  - CONTEXT: Serum paracetamol-protein adducts (PPAs) are a novel potential biomarker
      of paracetamol exposure. The relationship between serum PPA concentrations and
      reported paracetamol use in ambulatory adults has not been previously described.
      MATERIALS AND METHODS: This was a cross-sectional study of ambulatory adults. A
      detailed medication history was obtained from all subjects and subjects were
      stratified by reported paracetamol use in the 2 weeks prior to enrolment. Serum
      PPAs were measured in all subjects and correlated with reported dose, time of
      last ingestion and demographics. RESULTS: We enrolled 230 in the paracetamol
      exposure arm and 74 in the no exposure arm. 98/230 (42.6%)of subjects who
      reported paracetamol exposure had PPA detected and 68/74 (91.9%) of subjects who
      denied paracetamol exposure had no PPA detected. PPA concentrations were
      positively correlated with total paracetamol dose and with more recent ingestion.
      DISCUSSION: Detection of serum PPA generally reflects paracetamol exposure
      histories in ambulatory adults. Concentrations are well correlated with reported
      dose and time from last dose. CONCLUSIONS: Serum PPA can be detected with
      reported therapeutic use of paracetamol but may not be detected in all patients
      who report taking paracetamol.

PMID- 29179599
TI  - Fetal facial expressions in small-for-gestational-age and growth-restricted
      fetuses.
AB  - OBJECTIVE: To evaluate the frequencies of fetal facial expressions among
      appropriate-for-gestational-age (AGA), small-for-gestational-age (SGA), and
      growth-restricted (FGR) fetuses. METHODS: Four-dimensional (4D) ultrasound was
      used to examine the facial expressions of 50 AGA, 25 SGA, and six FGR fetuses
      between 28 and 35 weeks of gestation. The frequencies of seven facial expressions
      during 15-minute recordings were assessed. Comparison of facial expressions among
      the three groups was performed. RESULTS: Mouthing was the commonest facial
      expression at 28-35 weeks, and the frequency of mouthing was significantly higher
      than those of the other six facial expressions in AGA fetuses. Mouthing was the
      most frequent facial expression, but there was no significant difference in the
      frequency among mouthing, smiling and blinking in SGA fetuses. Moreover, mouthing
      displayed a significantly higher frequency than the other facial expressions,
      except for yawning, smiling, and blinking in FGR fetuses. However, there was no
      significant difference in the frequency of each facial expression among the three
      groups. CONCLUSIONS: Our results suggest that the frequencies of fetal facial
      expressions are not decreased in either SGA or FGR pregnancies. The absence of a
      decrease in the frequency of each fetal expression in FGR fetuses may be due to
      increased brain blood flow because of the brain-sparing effect. Moreover,
      accelerated maturation and development of the brain function, especially the
      central dopamine system, might be suspected in SGA and FGR fetuses.

PMID- 29179600
TI  - Nanovaccine for immunotherapy and reduced hepatitis-B virus in humanized model.
AB  - Chronic Hepatitis B Virus (HBV) infections are severe with weak antiviral immune
      responses. The lack of an appropriate small animal model for chronic hepatitis, a
      major hurdle for studying the immunotolerance and immunopathogenesis induced by
      hepatitis B viral (HBV) infection. In this study, for enhancing the antibody
      production efficiency the prepared polymeric HBsAg-loaded nanoparticles
      (nanovaccine) will be tested in immune-deficit mice, which suffer from chronic
      Hepatitis B virus. Vaccination of Balb/c mice by this prepared nanoparticles that
      were engrafted with peripheral blood mononuclear cells (PBMCs), which was already
      lethally irradiated and transplanted by the bone marrow of NOD (knockout mice)
      mice. In the present study, after the vaccination detected the high frequencies
      of immunoglobulin G (IgG)-secreting B cells and mitogen-responsive interferon-Y
      (IFN-Y) secreting T cells in serum, determined by specific ELISA technique.
      During the entire observation period, unvaccinated animals showed lower
      concentration of specific IgG secreting B cells and IFN-Y secreting T cells found
      in comparison to vaccinated mice group. Chronic HBV carrier PBMCs transplanted
      into the chimera failed to produce antigen and increased the antibodies
      production due to vaccination. Furthermore, another advantage was that the viral
      gene expression and viral DNA replication was no longer observed in vaccinated
      group. This prepared nanovaccine formulations is better for the cure of Hepatitis
      B viral infection carrier. Therefore, specific memory responses were elicited by
      vaccination with Hepatitis B virus surface (HBsAg) antigen of chimeric mice
      transplanted with PBMCs derived from HBV donors.

PMID- 29179601
TI  - An educational intervention to men for reducing environmental tobacco smoke
      exposure in their pregnant wives.
AB  - OBJECTIVE: To determine the effect of education based on health belief model
      (HBM) on the level of their pregnant wives' environmental tobacco smoke exposure
      (ETSE). METHODS: This interventional randomized study was conducted on 60
      cigarette smoking men who have exposed their pregnant wives to smoke during of
      their pregnancy. The HBM constructs and weekly ETSE were evaluated by using
      questionnaire. The intervention group received education with emphasis on the
      risks of cigarette's smoke on the pregnancy. Then right after the training and 6
      weeks after that, HBM constructs and 6 weeks after the training the weekly ETSE
      were evaluated again. RESULTS: Results showed a significant difference between
      the mean of perceived susceptibility, perceived benefits and barriers at intake
      and 6 weeks after the intervention in the intervention group. Also, the level of
      perceived susceptibility/severity and perceived barriers in both groups were
      significantly different 6 weeks after the intervention compared to intake time.
      The ETSE was significantly lower in the intervention group 6 weeks after the
      intervention in comparison to before the intervention and also to the control
      group. CONCLUSIONS: This study showed that education husbands would relatively
      improve their health beliefs and reduce the ETSE of their pregnant wives.

PMID- 29179602
TI  - Gene Transfer of ZMapp Antibodies Mediated by Recombinant Adeno-Associated Virus
      Protects Against Ebola Infections.
AB  - Vectored delivery of the ZMapp antibody cocktail (c2G4, c4G7, and c13C6) by using
      recombinant adeno-associated viruses (rAAVs) could be useful for preventive
      immunization against Ebola virus infections because rAAVs can generate long-term
      antibody expression. Three rAAVs (serotype 9) encoding chimeric ZMapp antibodies
      were produced by triple-plasmid transfection up to 10 L-scale in WAVE bioreactors
      using HEK293 cells grown in suspension/serum-free conditions. Efficacy of AAV
      c2G4 via intravenous (i.v.), intramuscular (i.m.), and intranasal (i.n.) routes
      of administration was evaluated in mice with two different doses of 2.7 * 1010
      and 13.0 * 1010 vector genomes (vg). The best protective efficacies after Ebola
      challenge were obtained with the i.v. and i.m. routes. Serum concentrations of
      ZMapp antibodies positively correlated with survivability. Efficacy of the rAAV
      ZMapp cocktail was then evaluated at a higher dose of 30.0 * 1010 vg. It
      conferred a more robust protection (90% i.v. and 60% i.m.) than rAAV-c4G7 (30%)
      and rAAV-c13C6 (70%), both administered separately at the same dose. Delivery of
      rAAV-c2G4 alone achieved up to 100% protection (100% i.v. and 90% i.m.) at the
      same dose. In conclusion, the preventive treatment was effective in mice.
      However, no advantage was observed for using the rAAV-ZMapp cocktail in
      comparison to the utilization of the single rAAV-c2G4.

PMID- 29179603
TI  - Nanocapsules for the co-delivery of selol and doxorubicin to breast
      adenocarcinoma 4T1 cells in vitro.
AB  - Nanocapsules (NCS-DOX) with an oily core of selol and a shell of poly(methyl
      vinyl ether-co-maleic anhydride) covalently conjugated to doxorubicin were
      developed. These nanocapsules are spherical, with an average hydrodynamic
      diameter of about 170 nm, and with negative zeta potential. NCS-DOX effectively
      co-delivered the selol and the doxorubicin into 4T1 cells and changed the
      intracellular distribution of DOX from the nuclei to the mitochondria. Moreover,
      a significantly increased cytotoxicity against 4T1 cells was observed, which is
      suggestive of additive or synergic effect of selol and doxorubicin. In
      conclusion, PVM/MA nanocapsules are suitable platforms to co-deliver drugs into
      cancer cells.

PMID- 29179604
TI  - Anterior screw fixation in type II odontoid fracture in an 18-month-old girl: a
      case report and review of the literature.
AB  - Odontoid fractures are among the rare cervical spine injuries in pediatric
      population and thus the optimal management of these injuries is controversial.
      The increasing trend in road traffic accidents and improvement in diagnostic
      modalities has led to an increased detection of odontoid fractures in pediatric
      population. We herein report type II odontoid fracture in an 18-month-old girl
      after falling off the motorcycle leading to hyperextension and flexion injury.
      She was successfully treated with anterior odontoid screw fixation followed by
      immobilization with hard collar for 2 months. Callus formation was detected after
      6 weeks and complete remodeling was observed at 6-year follow-up visit. This girl
      is among the youngest patients with type II odontoid fracture reported in
      literature being treated with anterior screw fixation. Further clinical series
      are needed to provide evidence for optimal management of odontoid fractures.

PMID- 29179605
TI  - Anticoagulant use in atrial fibrillation and risk of dementia: review of
      contemporary knowledge.
AB  - INTRODUCTION: Atrial fibrillation (AF) is strongly associated with dementia,
      including idiopathic dementias such as Alzheimer's disease. The relative risk of
      dementia is highest in AF patients 70 years and younger, and the burden of
      exposure to arrhythmia appears to underlie part of the risk. Areas covered:
      Anticoagulation choices and approach influence dementia risk. In warfarin
      patients, inadequate time spent in therapeutic range is highly associated with
      the increased dementia risk long-term. This risk is further accentuated with
      frequent over anticoagulation in patients also receiving aspirin. Direct oral
      anticoagulant therapies in early observational studies show that there is
      potential for improving long-term risk of dementia when compared to warfarin,
      although prospective trials are needed. AF and dementia are end manifestations of
      systemic disease; a systemic approach is needed with early treatment of shared
      risk factors to prevent disease presentation altogether. Expert commentary: In
      this review, we will bring together available data with regards to the link
      between anticoagulant use for AF and dementia. Anticoagulation initiation timing,
      use, and efficacy remain critical risk factors for dementia in AF patients and
      consequently provide opportunities to decrease risk.

PMID- 29179606
TI  - Membrane-initiated effects of Serelys(r) on proliferation and apoptosis of human
      breast cancer cells.
AB  - Herbal extracts used for the alleviation of postmenopausal symptoms might have a
      lower risk of breast cancer development than hormone therapy. Serelys(r) is a
      product composed of purified pollen cytoplasm extracts. Recent experimental data
      revealed that estrogens might trigger a further proliferative effect on breast
      cancer cells via the progesterone receptor membrane component-1 (PGRMC1) in
      addition to the proliferative effect via intracellularly located receptors. MCF-7
      and T47D cells were stably transfected with PGRMC1. Different concentrations of
      the extract alone and in combination with fixed concentrations of estradiol or a
      growth factor mixture were tested. Proliferation of treated cells was determined
      by the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide (MTT)-test
      and apoptosis was determined using a Cell Death Detection ELISA kit (CDD).
      Serelys(r) was neutral in the cell lines transfected or not transfected with
      PGRMC1. It was also neutral in combination with estradiol or growth factors in
      terms of cell proliferation and cell apoptosis. Thus in contrast to hormone
      therapy Serelys(r) appears to trigger no further breast cancer risk when applied
      in the post menopause to women, who do or do not overexpress PGRMC1. Overall
      Serelys(r) may be an effective alternative for alleviating postmenopausal
      symptoms without increasing breast cancer risk.

PMID- 29179607
TI  - Novel pyochelin-based PEGylated liposomes for enhanced delivery of antibiotics
      against resistant clinical isolates of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a problematic human pathogen resistant to almost all
      available antibiotics. The important prerequisite for these drugs to target this
      bacterium is an efficient delivery system. Siderophore-mediated drug delivery
      system is a promising approach to carry out antibiotics to the cells. Pyochelin,
      a siderophore of P. aeruginosa, was successfully synthesized in a five-step
      procedure. PEGylated liposomal pyochelin-antibiotic (L-Pch-Ab) carrier was
      fabricated by thin-film hydration method. L-Pch-Ab had an average size of 90.31
      +/- 0.11 nm holding a negative zeta potential at -54.12 +/- 0.03 mV (PDI <2). The
      MIC determined by broth dilution method against three clinical strains isolated
      from burn wounds showed that L-Pch-Ab significantly reduced (<=16 ug/ml) the MIC
      values than those of free antibiotics. In the time kill assay, L-Pch-Ab was
      bactericidal against all strains at most time intervals at 2 * and 4 * MIC up to
      24 h. TEM observations revealed that L-Pch-Ab was actively taken up by P.
      aeruginosa and exhibited membrane deformation within 2 h. Developed L-Pch-Ab
      fused intimately with the outer membrane of MDRPa and exhibited effective
      antibacterial activity than free Ab. Furthermore, L-Pch-Ab kills MDRPa within
      infected HaCaT keratinocytes without any cytotoxic effects at 4* MIC
      concentrations after 72 h. Thus, the specific targeting of L-Pch-Ab with its
      higher efficacy to deliver drug by limiting the toxicity will be a novel approach
      to fight infections caused by P. aeruginosa.

PMID- 29179608
TI  - Surgical management of meningoencephalocele in temporal bone associated with
      pharmacoresistant epilepsy: report of two cases.
AB  - We report good outcome after surgical treatment of two patients with
      meningoencephalocele associated with pharmacoresistant temporal lobe epilepsy.
      Surgical management of meningoencephaloceles may result in seizure freedom,
      although optimal surgical strategy is still controversial.

PMID- 29179609
TI  - Staged pallidotomy: MRI and clinical follow-up in status dystonicus.
AB  - PURPOSE: We report on a patient affected by Status Distonicus who was treated
      with Deep Brain Stimulation electrodes implanted in the Globus Pallidus internus
      (Gpi) and used for serial radiofrequency lesions. MATERIALS AND METHODS: The
      evolution of radiofrequency lesions was monitored by post-operative and late
      Magnetic Resonance Imaging (MRI). After the first lesion the patient did improve,
      though not in a significant fashion. Therefore, three further radiofrequency
      lesions were delivered 2, 4 and 6 days respectively after surgery with subsequent
      improvement of dystonic movements. RESULTS: MRI scans performed at 8 days, 3
      months, and 6 months after surgery showed a diffuse T2-hyperintense and T1
      hypointense GPi signal alteration which progressively decreased over time.
      CONCLUSION: We confirm that the possibility to stage pallidotomies over time
      using a couple of new contacts is a safe and efficacious procedure in treating SD
      patients where the lesions themselves are limited by the appearance of side
      effects, or in patients showing a poor response to a single lesion. As far as we
      know, this is the first description of MRI evolution and monitoring of a staged
      pallidotomy.

PMID- 29179610
TI  - A Tug-of-War between Cryptochrome and the Visual System Allows the Adaptation of
      Evening Activity to Long Photoperiods in Drosophila melanogaster.
AB  - In many animals, the circadian clock plays a role in adapting to the coming
      season by measuring day length. The mechanism for measuring day length and its
      neuronal circuits remains elusive, however. Under laboratory conditions, the
      fruit fly, Drosophila melanogaster, displays 2 activity peaks: one in the morning
      and one in the evening. These peaks appear to be regulated by 2 separate
      circadian oscillators (the morning and evening oscillators) that reside in
      different subsets of pacemaker clock neurons in the brain. The morning and
      evening activity peaks can flexibly change their phases to adapt to different
      photoperiods by tracking dawn and dusk, respectively. In this study, we found
      that cryptochrome (CRY) in the evening oscillators (the fifth small ventral
      lateral neuron [5th s-LNv] and the dorsal lateral neurons [LNds]) limits the
      ability of the evening peak to track dusk during long days. In contrast, light
      signaling from the external photoreceptors (compound eyes, ocelli, and Hofbauer
      Buchner eyelets) increases the ability of the evening peak to track dusk. At the
      molecular level, CRY signaling dampens the amplitude of PAR-domain protein 1
      (PDP1) oscillations in most clock neurons during long days, whereas signaling
      from the visual system increases these amplitudes. Thus, our results suggest that
      light inputs from the two major circadian photoreceptors, CRY and the visual
      system, have opposite effects on day length adaptation. Their tug-of-war appears
      to determine the precise phase adjustment of evening activity.

PMID- 29179611
TI  - Sensitivity to Pigment-Dispersing Factor (PDF) Is Cell-Type Specific among PDF
      Expressing Circadian Clock Neurons in the Madeira Cockroach.
AB  - Transplantation studies have pinpointed the circadian clock of the Madeira
      cockroach to the accessory medulla (AME) of the brain's optic lobes. The AME is
      innervated by approximately 240 adjacent neuropeptidergic neurons, including 12
      pigment-dispersing factor (PDF)-expressing neurons anterior to the AME (aPDFMEs).
      Four of the aPDFMEs project contralaterally, controlling locomotor activity
      rhythms of the night-active cockroach. The present in vitro Ca2+ imaging analysis
      focuses on contralaterally projecting AME neurons and their responses to PDF,
      GABA, and acetylcholine (ACh). First, rhodamine-dextran backfills from the
      contralateral optic stalk identified contralaterally projecting AME neurons,
      which were then dispersed in primary cell cultures. After characterization of
      PDF, GABA, and ACh responses, PDF immunocytochemistry identified ipsilaterally
      and contralaterally projecting PDFMEs. All PDF-sensitive clock neurons, PDF
      immunoreactive clock neurons, and the majority of ipsilaterally and
      contralaterally projecting cells were excited by ACh. GABA inhibited all PDF
      expressing clock neurons, and about half of other ipsilaterally projecting and
      most contralaterally projecting clock neurons. For the first time, we identified
      PDF autoreceptors in PDF-secreting cockroach circadian pacemakers. The medium
      sized aPDFMEs and all other contralaterally projecting PDF-sensitive clock cells
      were inhibited by PDF. The ipsilaterally remaining small PDF-sensitive clock
      cells were activated by PDF. Only the largest aPDFME did not express PDF
      autoreceptors. We hypothesize that opposing PDF signaling generates 2 different
      ensembles of clock cells with antiphasic activity, regulating and maintaining a
      constant phase relationship between rest and activity cycles of the night-active
      cockroach.

PMID- 29179612
TI  - Self-reference enhances relational memory in young and older adults.
AB  - The present study investigated the influence of self-reference on two kinds of
      relational memory, internal source memory and associative memory, in young and
      older adults. Participants encoded object-location word pairs using the
      strategies of imagination and sentence generation, either with reference to
      themselves or to a famous other (i.e., George Clooney or Oprah Winfrey). Both
      young and older adults showed memory benefits in the self-reference conditions
      compared to other-reference conditions on both tests, and the self-referential
      effects in older adults were not limited by low memory or executive functioning.
      These results suggest that self-reference can benefit relational memory in older
      adults relatively independently of basic memory and executive functions.

PMID- 29179613
TI  - Reading Fluency and Students With Reading Disabilities: How Fast Is Fast Enough
      to Promote Reading Comprehension?
AB  - The goal of improving reading rate and fluency is to positively impact reading
      comprehension; however, it is unclear how fast students with learning
      disabilities (LD) need to read to reap this benefit. The purpose of this research
      was to identify the point of diminishing return for students who were dysfluent
      readers. Participants included 337 students with reading difficulties in second
      and fourth grade (61% eligible for special education; 80% with a diagnosis of LD
      in the area of reading) and 150 typical readers from the same general education
      classes. LOESS (LOcal regrESSion) plots (logistic regression) were used to
      determine where linear relations between reading rate and comprehension broke
      down for these students: the rate at which getting faster no longer contributed
      clearly to reading comprehension improvement. Although typical readers in this
      sample showed patterns of oral reading rate and comprehension similar to students
      in other studies, patterns for students with reading difficulties differed. For
      dysfluent readers, improving reading rate improved comprehension only in the
      bands between 35 and 75 words correct per minute in second grade and between 40
      and 90 words correct in fourth grade. Reading at faster rates revealed no clear
      advantage for reading comprehension.

PMID- 29179614
TI  - Long non-coding RNA ZFAS1 sponges miR-484 to promote cell proliferation and
      invasion in colorectal cancer.
AB  - The incidence and mortality rate of colorectal cancer (CRC) have been
      significantly increasing. However, mechanisms involved in CRC progression are
      still unclear. LncRNA ZFAS1 has been verified as oncogenic molecular in a series
      of tumors, including CRC. However, the underlying mechanism of ZFAS1 in CRC
      carcinogenesis remains unclear. In the present study, our data showed that ZFAS1
      expression was significantly upregulated in CRC tissues and cell lines.
      Correlation analysis showed that high ZFAS1 expression was significantly
      associated with Helicobacter pylori infection, lymph nodes metastasis, advanced
      TNM stage and poor overall survival of CRC patients. Loss-of-function experiments
      revealed that ZFAS1 inhibition could markedly suppress CRC cells proliferation
      and invasion both in vitro and in vivo. Bioinformatics analysis and luciferase
      reporter assay revealed that ZFAS1 directly interacted with miR-484. Rescue
      experiments showed that miR-484 inhibitor reversed the tumor suppressing roles of
      ZFAS1 knockdown on CRC cells. Therefore, our study suggested that ZFAS1 could act
      as an oncogene in CRC tumorigenesis, and discovered the functional regulatory
      pathway of ZFAS1 sponging miR-484.

PMID- 29179615
TI  - Phenolic metabolites, biological activities, and isolated compounds of Terminalia
      muelleri extract.
AB  - CONTEXT: Terminalia muelleri Benth. (Combretaceae), is rich with phenolics that
      have antioxidant and cytotoxic activities. No screening studies were published
      before on T. muelleri. OBJECTIVE: The study focused on isolation and
      identification of secondary metabolites from aqueous methanol leaf extract of T.
      muelleri and evaluation of its biological activities. MATERIALS AND METHODS: The
      n-butanol extract was chromatographed on polyamide 6, and eluted with H2O/MeOH
      mixtures of decreasing polarity, then separated by different chromatographic
      tools that yielded 10 phenolic compounds. The antioxidant activity of the extract
      was evaluated by investigating its total phenolic and flavonoid content and DPPH
      scavenging effectiveness. The extract and the two acylated flavones were
      evaluated for their anticancer activity towards MCF-7 and PC3 cancer cell lines.
      Molecular docking study of the acylated flavones was performed against
      topoisomerase enzyme. RESULTS AND DISCUSSION: Two acylated flavonoids, apigenin-8
      C-(2"-O-galloyl) glucoside 1 and luteolin-8-C-(2"-O-galloyl) glucoside 2, were
      isolated and identified for the second time in nature, with eight tannins (3-10),
      from the leaves of T. muelleri. The extract and compound 10 showed the most
      significant antioxidant activity (IC50 = 3.55 and 6.34 MUg/mL), respectively. The
      total extract and compound 2 demonstrated cytotoxic effect against MCF-7 with
      IC50 = 29.7 and 45.2 MUg/mL respectively, while compound 1 showed cytotoxic
      effect against PC3 (IC50 = 40.8 MUg/mL). The docking study of compounds 1 and 2
      confirmed unique binding mode in the active site of human DNA topoisomerase
      enzyme. CONCLUSIONS: Terminalia muelleri is a promising medicinal plant as it
      possesses high antioxidant activity and moderate cytotoxic activity against MCF
      7.

PMID- 29179616
TI  - Executive Function Variation in Children With Conduct Problems: Influences of
      Coexisting Reading Difficulties.
AB  - It is unknown whether children with conduct problems (CP) and poor reading (PR)
      skills exhibit more profound executive function impairments than children with CP
      only and whether such impairments are explained by coexisting PR. Executive
      functions were compared in four groups of 7- to 8-year-old children: 26 CP only,
      35 PR only, 27 CP-PR, and 31 comparison (COM) children with neither CP nor PR.
      The Conners' Teacher Rating Scale-28 and a sentence completion reading test were
      used to assess CP and PR skills. The Wechsler Intelligence Scale for Children
      Third Edition Backward Digit Span, the Conners' Continuous Performance Test, and
      the Tower of London were used to assess three aspects of executive function:
      verbal working memory, response inhibition, and planning, respectively. The CP-PR
      group had lower verbal working memory than the CP-only and COM groups, but the
      difference was not significant after intellectual ability, inattention, and
      hyperactivity were controlled. The CP-PR group made more errors in the planning
      task (rule violations) than the COM and CP-only groups, but the difference was
      not significant after intellectual ability was controlled. No significant group
      differences were found in response inhibition. A specific PR group effect was
      found for verbal working memory. Children with CP-PR have more prominent
      executive function impairments that cannot be attributed to coexisting PR.

PMID- 29179617
TI  - Twelve tips for incorporating and teaching sexual and gender minority health in
      medical school curricula.
AB  - The World Health Organization has identified many barriers to improving the
      health of lesbian, gay, bisexual, and transgender (LGBT) patients, including
      challenges to incorporating and teaching about healthcare for such patients,
      which we call "sexual and gender minority" (SGM) health content. These challenges
      include structural and logistical barriers to incorporating SGM health content
      into undergraduate medical curricula, as well as lack of support in identifying
      high-quality pedagogical methods for teaching this material. Here, we provide
      twelve tips for incorporating and teaching SGM health curricular content in
      undergraduate medical education, including resources and strategies to support
      individual educators. Based on our success in developing and implementing this
      content, we believe that our approach can be effectively used by individual
      educators aiming to incorporate SGM health curricular material into their
      teaching, and to support individuals or groups championing the inclusion of a SGM
      health topical sequence in medical curricula.

PMID- 29179618
TI  - Trends in research productivity of residents applying for orthopedic sports
      medicine fellowship.
AB  - OBJECTIVES: Though there are no research requirements to match into an
      orthopaedic sports medicine fellowship, many applicants are productive in
      research endeavors during residency. We hypothesize that the number of
      publications by Orthopaedic sports medicine applicants are increasing. METHODS: A
      list of current and recent sports medicine fellows was compiled from publicly
      accessible information on sports medicine fellowship websites. Articles published
      while the fellow was a resident were identified via publicly available search
      engines. The following information was collected: year of fellowship and years of
      residency, fellowship program, geographic location of fellowship program, total
      number of publications (noting specifically first and last author publications),
      number of publications in high impact orthopaedic journals (AJSM, JBJS Am, JSES,
      or Arthroscopy). RESULTS: Overall, 189 fellowship-matched surgeons from 2010 -
      2017 were identified. There were 746 publications (average of 3.95 per fellow),
      with 218 (29.2%) in high impact orthopaedic journals. Surgeons who completed
      their fellowship during the 2016-17 academic year, published on average 5.42
      publications per fellow. Fellowship applicants in the Northeast region had the
      highest number of total publications (359 publications, 48.1% of all
      publications; 6.41 publications per fellow). Applicants were listed most often as
      middle authors (462 publications, 61.9%). CONCLUSIONS: There has been an overall
      increase in the number of publications among sports medicine fellowship
      applicants in the last several academic years. Fellowship programs in the
      northeast United States tended to match applicants with a higher number of
      publications.

PMID- 29179620
TI  - A Novel Method for Quantifying Human In Situ Whole Brain Deformation under
      Rotational Loading Using Sonomicrometry.
AB  - Traumatic brain injuries (TBI) are one of the least understood injuries to the
      body. Finite element (FE) models of the brain have been crucial for understanding
      concussion and for developing injury mitigation systems; however, the
      experimental brain deformation data currently used to validate these models are
      limited. The objective of this study was to develop a methodology for the
      investigation of in situ three-dimensional brain deformation during pure
      rotational loading of the head, using sonomicrometry. Sonomicrometry uses
      ultrasonic pulses to measure the dynamic distances between piezoelectric crystals
      implanted in any sound-transmitting media. A human cadaveric head-neck specimen
      was acquired 14 h postmortem and was instrumented with an array of 32 small
      sonomicrometry crystals embedded in the head: 24 crystals were implanted in the
      brain, and 8 were fixed to the inner skull. A dynamic rotation was then applied
      to the head using a closed-loop controlled test device. Four pulses with
      different severity levels were applied around three orthogonal anatomical axes of
      rotation. A repeated test of the highest severity rotation was conducted in each
      axis to assess repeatability. All tests were completed within 56 h postmortem.
      Overall, the combined experimental and sonomicrometry methods were demonstrated
      to reliably and repeatedly capture three-dimensional dynamic deformation of an
      intact human brain. These methods provide a framework for using sonomicrometry to
      acquire multidimensional experimental data required for FE model development and
      validation, and will lend insight into the deformations sustained by the brain
      during impact.

PMID- 29179619
TI  - Urban fine particulate matter (PM2.5) exposure destroys blood-testis barrier
      (BTB) integrity through excessive ROS-mediated autophagy.
AB  - CONTEXT: Blood-testis barrier (BTB), constituted by tight junctions (TJs),
      adherens junctions and gap junctions, is important for spermatogenesis. PM2.5 is
      known to impair testicular functions and reproduction. However, its effects on
      BTB and the underlying mechanisms remain obscure. OBJECTIVE: To investigate the
      roles of autophagy in BTB toxicity induced by PM2.5. MATERIALS AND METHODS:
      Sprague-Dawley rats were developmentally exposed to normal saline (NS) or PM2.5
      with the doses of 9 mg/kg b.w. and 24 mg/kg b.w. via intratracheal instillation
      for seven weeks. Success rate of mating, sperm quality, testicular morphology,
      expressions of BTB junction proteins and autophagy-related proteins were
      detected. In addition, expressions of oxidative stress markers were also
      analyzed. RESULTS: Our results demonstrated that developmental PM2.5 exposure
      induced noticeable decreased fertility, significantly reduced sperm count,
      increased sperm abnormality rate and severe testicular damage in histomorphology.
      The expressions of TJ (such as ZO-1 and occludin), gap junction (such as
      connexin43) were down-regulated significantly after PM2.5 treatment.
      Intriguingly, PM2.5 simultaneously increased the number of autophagosomes and the
      levels of autophagy marker LC3-II and p62, suggesting that the accumulated
      autophagosomes resulted from impaired autophagy degradation. Moreover, the
      expressions of HO-1 levels remarkably increased and expression levels of Gpx and
      SOD were significantly decreased after PM2.5 exposure. Vitamins E and C could
      alleviate the PM2.5-induced oxidative stress, reverse the autophagy defect and
      restore the BTB impairment. CONCLUSIONS: Taken together, the results suggest that
      PM2.5 exposure destroys BTB integrity through excessive ROS-mediated autophagy.
      Our finding could contribute to a better understanding of PM2.5-induced male
      reproductive toxicity.

PMID- 29179621
TI  - Erythropoietin Attenuates the Brain Edema Response after Experimental Traumatic
      Brain Injury.
AB  - Erythropoietin (EPO) has neuroprotective effects in multiple central nervous
      system (CNS) injury models; however EPO's effects on traumatic brain edema are
      elusive. To explore EPO as an intervention in traumatic brain edema, male Sprague
      Dawley (SD) rats were subjected to blunt, controlled traumatic brain injury
      (TBI). Animals were randomized to EPO 5000 IU/kg or saline (control group)
      intraperitoneally within 30 min after trauma and once daily for 4 consecutive
      days. Brain MRI, immunohistofluorescence, immunohistochemistry, and quantitative
      protein analysis were performed at days 1 and 4 post- trauma. EPO significantly
      prevented the loss of the tight junction protein zona occludens 1 (ZO-1) observed
      in control animals after trauma. The decrease of ZO-1 in the control group was
      associated with an immunoglobulin (Ig)G increase in the perilesional parenchyma,
      indicating blood-brain barrier (BBB) dysfunction and increased permeability. EPO
      treatment attenuated decrease in apparent diffusion coefficient (ADC) after
      trauma, suggesting a reduction of cytotoxic edema, and reduced the IgG leakage,
      indicating that EPO contributed to preserve BBB integrity and attenuated
      vasogenic edema. Animals treated with EPO demonstrated conserved levels of
      aquaporin 4 (AQP4) protein expression in the perilesional area, whereas control
      animals showed a reduction of AQP4. We show that post TBI administration of EPO
      decreases early cytotoxic brain edema and preserves structural and functional
      properties of the BBB, leading to attenuation of the vasogenic edema response.
      The data support that the mechanisms involve preservation of the tight junction
      protein ZO-1 and the water channel AQP4, and indicate that treatment with EPO may
      have beneficial effects on the brain edema response following TBI.

PMID- 29179623
TI  - In Defense of the Questionable: Defining the Basis of Research Scientists'
      Engagement in Questionable Research Practices.
AB  - National Institutes of Health principal investigators reported their perceptions
      of the ethical defensibility, prevalence in their field, and their personal
      willingness to engage in questionable research practices (QRPs). Using ethical
      defensibility ratings, an exploratory factor analysis yielded a two-factor
      solution: behaviors considered unambiguously ethically indefensible and behaviors
      whose ethical defensibility was more ambiguous. In addition, increasing
      perceptions that QRPs affect science predicted reduced acceptability of QRPs,
      whereas increasing beliefs that QRPs are normative or necessary for career
      success predicted increased acceptability of QRPs. Perceptions that QRPs are
      risky were unrelated to QRP acceptability but predicted reduced extramural
      funding (i.e., researchers' lifetime extramural grants and total funding
      secured). These results identify risk (i.e., beliefs that QRPs are normative to
      stay competitive in one's field) and protective factors (i.e., beliefs that QRPs
      have a significant negative impact on society) related to QRP endorsement that
      could inform educational interventions for training research scientists.

PMID- 29179622
TI  - Traumatic Brain Injury Impairs Myogenic Constriction of Cerebral Arteries: Role
      of Mitochondria-Derived H2O2 and TRPV4-Dependent Activation of BKca Channels.
AB  - Traumatic brain injury (TBI) impairs autoregulation of cerebral blood flow, which
      contributes to the development of secondary brain injury, increasing mortality of
      patients. Impairment of pressure-induced myogenic constriction of cerebral
      arteries plays a critical role in autoregulatory dysfunction; however, the
      underlying cellular and molecular mechanisms are not well understood. To
      determine the role of mitochondria-derived H2O2 and large-conductance calcium
      activated potassium channels (BKCa) in myogenic autoregulatory dysfunction,
      middle cerebral arteries (MCAs) were isolated from rats with severe weight drop
      impact acceleration brain injury. We found that 24 h post-TBI MCAs exhibited
      impaired myogenic constriction, which was restored by treatment with a
      mitochondria-targeted antioxidant (mitoTEMPO), by scavenging of H2O2
      (polyethylene glycol [PEG]-catalase) and by blocking both BKCa channels
      (paxilline) and transient receptor potential cation channel subfamily V member 4
      (TRPV4) channels (HC 067047). Further, exogenous administration of H2O2 elicited
      significant dilation of MCAs, which was inhibited by blocking either BKCa or
      TRPV4 channels. Vasodilation induced by the TRPV4 agonist GSK1016790A was
      inhibited by paxilline. In cultured vascular smooth muscle cells H2O2 activated
      BKCa currents, which were inhibited by blockade of TRPV4 channels. Collectively,
      our results suggest that after TBI, excessive mitochondria-derived H2O2 activates
      BKCa channels via a TRPV4-dependent pathway in the vascular smooth muscle cells,
      which impairs pressure-induced constriction of cerebral arteries. Future studies
      should elucidate the therapeutic potential of pharmacological targeting of this
      pathway in TBI, to restore autoregulatory function in order to prevent secondary
      brain damage and decrease mortality.

PMID- 29179624
TI  - Invited Commentary on Dube et al. (Perceptions of Equipoise, Risk/Benefit Ratios,
      and "Otherwise Healthy Volunteers" in the Context of Early-Phase HIV Cure
      Research in the United States-A Qualitative Inquiry): Are HIV-Infected Candidates
      for Participation in Risky Cure-Related Studies Otherwise Healthy?

PMID- 29179625
TI  - The Ethics of Health Care Delivery in a Pediatric Malaria Vaccine Trial: The
      Perspectives of Stakeholders From Ghana and Tanzania.
AB  - This study explores ethical issues raised in providing medical care to
      participants and communities of low-resource settings involved in a Phase II/III
      pediatric malaria vaccine trial (PMVT). We conducted 52 key informant interviews
      with major stakeholders of an international multi-center PMVT (GSK/PATH-MVI
      RTS,S) (NCT00866619) in Ghana and Tanzania. Based on their stakeholder
      experiences, the responses fell into three main themes: (a) undue inducement, (b)
      community disparities, and (c) broad therapeutic misconceptions. The study
      identified the critical ethical aspects, from the perspectives of stakeholders,
      of delivering health care during a PMVT. The study showed that integrating
      research into health care services needs to be addressed in a manner that upholds
      the favorable risk-benefit ratio of research and attends to the health needs of
      local populations. The implementation of research should aim to improve local
      standards of care through building a collaborative agenda with local institutions
      and systems of health.

PMID- 29179626
TI  - Reply to Commentary: "Are HIV-Infected Candidates for Participation in Risky Cure
      Related Studies Otherwise Healthy?"
AB  - We respond to Eyal et al.'s commentary focusing on how people living with HIV
      participating in HIV cure-related studies are defined. We argue that the types of
      participants enrolled in research cannot be dissociated from the study
      interventions, the types of anticipated risks, and the background standard of
      care. As the field of HIV cure research advances, more nuance and granularity
      will be needed to define research criteria and acceptable risk/benefit ratios for
      cure study participants, as well as specific tiered protocol designs that serve
      to protect various participant populations from untoward risks, especially in
      very early phase research with interventions known to have potentially serious
      toxicities. We highlight key lessons from the ACTIVATE study involving a latency
      reversing agent, Panobinostat, for HIV cure study design involving "otherwise
      healthy volunteers".

PMID- 29179627
TI  - Delirium is associated with increased mortality in the geriatric population.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of delirium
      and its association with mortality rates in elderly inpatients. METHODS: The
      medical records of 1435 patients over 65 years old who were treated at a regional
      university hospital and were referred to the university's Consultation and
      Liaison Psychiatry Clinic for psychological evaluation were retrospectively
      analyzed. Patients with and without a diagnosis of delirium were compared. The
      National Survival Database was used to determine mortality rates. RESULTS: The
      prevalence of delirium was 25.5%. The delirium group was older (p < .0001) and
      had a larger proportion of males (p < .0001). Mortality rate was higher in the
      delirium group at 1, 2, 3, 4, and 5 years (p < .0001 for all). Age, gender, lower
      urinary system diseases, chronic liver disease, solid hematologic malignancy,
      infections, and Alzheimer's disease emerged as significant parameters associated
      with mortality. Multivariate analysis of these parameters indicated that comorbid
      diseases (lower urinary system diseases, chronic liver disease, solid hematologic
      malignancy, infections, and Alzheimer's disease) are risk factors for mortality
      independent of demographic data such as age and gender. CONCLUSIONS: Independent
      of all other factors, delirium is associated with higher mortality risk.

PMID- 29179628
TI  - Pregnancy after uterine artery embolization using GelfoamTM.
AB  - We present a case study of a patient who underwent uterine artery embolization
      (UAE) using GelfoamTM (Pfizer, New York, NY, USA) and had a subsequent pregnancy.
      Our patient, a 38-year-old female (4 Gravida/2 Para), underwent UAE for treatment
      of symptomatic myoma in September 2005. At the patient's seven-month post
      procedure visit, she experienced a 43.9% volume reduction in uterine size and
      74.5% reduction in volume of the largest fibroid and relief of bulk symptoms and
      menorrhagia. The patient had a term delivery of healthy twin infants 15 months
      post embolization.

PMID- 29179630
TI  - Joining, belonging, and re-valuing: a process of meaning-making through group
      participation in a mental health lifestyle intervention.
AB  - BACKGROUND: Balancing Everyday Life (BEL), a new group-based intervention for
      mental health service users, was implemented in Sweden. Mental health service
      users often experience group interventions as meaningful, but knowledge of the
      process of meaning-making in a group is lacking. AIM: To explore participants'
      perceptions of the group in the Balancing Everyday Life (BEL) lifestyle
      intervention; specifically, personal experiences of what brings meaning when
      participating in a group. METHODS: This qualitative Grounded Theory study
      included 26 interviews with 19 BEL participants. RESULTS: A process of meaning
      making in a group was constructed: Joining with others: from feeling alone to
      connected, A sense of belonging: mutual support and understanding, and Re-valuing
      Self: respect and self-worth. No longer feeling alone contributed to meaning.
      Peers and group leaders were considered important parts of the group, and
      participants appreciated feeling understood, respected, and helping others.
      CONCLUSION: The proposed process of meaning-making, as well as 'Joining' as a
      unique step, seems to be new contributions which could help practitioners when
      organizing groups. Overcoming fear of joining could break a cycle of isolation
      and lead to connecting and belonging. The value of participants finding purpose
      through helping others should be further explored.

PMID- 29179629
TI  - Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain.
AB  - Despite 253,000 spinal cord injury (SCI) patients in the United States, little is
      known about how SCI affects brain networks. Spinal MRI provides only structural
      information with no insight into functional connectivity. Resting-state
      functional MRI (RS-fMRI) quantifies network connectivity through the
      identification of resting-state networks (RSNs) and allows detection of
      functionally relevant changes during disease. Given the robust network of spinal
      cord afferents to the brain, we hypothesized that SCI produces meaningful changes
      in brain RSNs. RS-fMRIs and functional assessments were performed on 10 SCI
      subjects. Blood oxygen-dependent RS-fMRI sequences were acquired. Seed-based
      correlation mapping was performed using five RSNs: default-mode (DMN), dorsal
      attention (DAN), salience (SAL), control (CON), and somatomotor (SMN). RSNs were
      compared with normal control subjects using false-discovery rate-corrected two
      way t tests. SCI reduced brain network connectivity within the SAL, SMN, and DMN
      and disrupted anti-correlated connectivity between CON and SMN. When divided into
      separate cohorts, complete but not incomplete SCI disrupted connectivity within
      SAL, DAN, SMN and DMN and between CON and SMN. Finally, connectivity changed over
      time after SCI: the primary motor cortex decreased connectivity with the primary
      somatosensory cortex, the visual cortex decreased connectivity with the primary
      motor cortex, and the visual cortex decreased connectivity with the sensory
      parietal cortex. These unique findings demonstrate the functional network
      plasticity that occurs in the brain as a result of injury to the spinal cord.
      Connectivity changes after SCI may serve as biomarkers to predict functional
      recovery following an SCI and guide future therapy.

PMID- 29179631
TI  - Bulimic Symptomatology Among Male Collegiate Athletes: A Test of an Etiological
      Model.
AB  - We tested Petrie and Greenleaf's psychosocial model in relation to male athletes'
      bulimic symptomatology. Through structural equation modeling, we cross
      sectionally examined the direct and indirect effects of general and sport
      specific appearance pressures, internalization, body satisfaction, drive for
      muscularity, negative affect, and dietary restraint on bulimic symptomatology.
      Participants were U.S. male collegiate athletes (N = 698; Mage = 19.87 years)
      representing 17 sports. With minor respecifications, the model had acceptable
      fit, and the psychosocial variables explained 48% of the bulimic symptomatology
      variance. Although all variable paths were significant, sport pressures, such as
      from coaches and teammates about weight, importance of appearance, and looking
      good in a uniform, were the most salient latent variable. Athletes' engagement in
      muscle-building behaviors added uniquely and substantively as well. Our analysis
      begins to clarify the complex interactions among these psychosocial variables in
      understanding male athletes' bulimic symptomatology and provides a base from
      which to develop prevention programming.

PMID- 29179632
TI  - Prediction of the ablated area prior to radiofrequency ablation for liver tumor
      under CT guidance.
AB  - PURPOSE: To evaluate the usefulness of a method we developed to predict the
      ablation area at the time of CT guided radiofrequency (RF) ablation for liver
      tumors on a CT workstation. MATERIAL AND METHODS: Ten tumors (mean diameter 15.5
      mm, range, 9.0-21.5 mm) in seven patients with hepatocellular carcinoma for which
      CT guided RF ablation was performed were subjects of this study. After advancing
      the electrode, plain CT was obtained. Then a simulated ball to predict the
      ablated area was created on the workstation. After confirming that the tumor was
      sufficiently within the ball, ablation was performed. The distance of the edge of
      the actual ablated area from that of the predicted ablated area was measured at
      six points in three cross-sectional directions on CT images after ablation.
      RESULTS: The procedures were successfully performed without complications. No
      local recurrence occurred. Mean absolute value of the distance of the gap between
      the actual and predicted ablated areas was 3.06 +/- 2.18 mm (range: 0 to 9 mm).
      At 29 (55.8%) points, the actual ablated area was smaller than the predicted
      ablated area; it was larger in 17 (32.7%), and was the same in 6 (11.5%) points.
      CONCLUSION: Our method produces an acceptable simulation during RF ablation under
      CT guidance.

PMID- 29179633
TI  - A concept for electromagnetic navigated targeting of liver tumors using an
      angiographic approach.
AB  - BACKGROUND: The benefits of using navigation technology for percutaneous local
      ablation of selected hepatocellular carcinoma (HCC) have been shown. Due to
      additional efforts in the procedural workflow, barriers to introducing navigation
      systems on a broad clinical level remain high. In this work, initial steps toward
      a novel concept for simple and precise targeting of HCC are evaluated. MATERIAL
      AND METHODS: The proposed technique is based on an angiographic approach using an
      intrahepatic electromagnetic (EM) reference, for consecutive percutaneous
      navigated positioning of ablation probes. We evaluated the environmental
      influence of the angiography suite on EM tracking accuracy, the measurement of a
      3 D offset from two 2 D fluoroscopy images, and the accuracy and efficiency of
      the proposed approach in a porcine liver model. RESULTS: The C-arm had a major
      influence on EM tracking accuracy, with an error up to 3.8 mm. The methodology
      applied for measurement of a 3 D offset from 2 D fluoroscopy images was confirmed
      to be feasible with a mean error of 0.76 mm. In the porcine liver model
      experiment, the overall target positioning error (TPE) was 2.0 mm and time for
      navigated targeting was 17.9 seconds, when using a tracked ablation probe.
      CONCLUSIONS: The initial methodology of the proposed technique was confirmed to
      be feasible, introducing a novel concept for simple and precise navigated
      targeting of HCC.

PMID- 29179634
TI  - Azacytidine in combination with tyrosine kinase inhibitors induced durable
      responses in patients with advanced phase chronic myelogenous leukemia.
AB  - Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in
      outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or
      myeloid blast crisis patients or of de novo Philadelphia chromosome-positive
      acute myeloid leukemia remains poor. We conducted a retrospective study on
      patients with advanced phase disease treated with a TKI and azacytidine. Sixteen
      patients were eligible. Median age was 64.9 years, the median number of previous
      therapies was 2.5 lines, and median follow-up was 23.1 months. Hematologic
      response (HR) rate was 81.3%. Median overall survival (OS), event free survival
      and relapse-free survival (RFS) were 31.5, 23.3, and 32.2 months, respectively.
      All except one patient were treated as out-patients after the first cycle. Five
      patients were bridged to allogenic hematopoietic stem cells transplant. The
      combination of a TKI and azacytidine is a safe and efficient regiment for
      patients with CML patients in advanced phases.

PMID- 29179635
TI  - The impact of informed self-assessment on the development of medical students'
      learning goals.
AB  - PURPOSE: This study investigates the contributions of self-assessment (SA) and
      external feedback on the development of learning goals (LG) and the influence on
      LG recall and implementation in medical students. METHODS: Following a
      standardized patient (SP) assessment, 168 pre-clinical medical students completed
      a SA, received SP feedback and created a LG. LG were categorized by source. Two
      weeks later, students recalled LG and described implementation. Chi-squared
      analyses were used to test the associations. RESULTS: SA influenced LG for 82.8%
      of students whereas SP feedback influenced LG for 45.9%. Students rarely
      generated LG based on SA when they received discordant feedback (5.4%), but
      sometimes incorporated feedback discordant from their SA into LG (14.9%).
      Students who created LG based on SP feedback were more likely to recall LG than
      those who created LG based on SA, 89.7 versus 67.6%, p < 0.05 and implement their
      LG, 72.4 versus 48.9%, chi2(1) = 5.3, p = 0.017. Students who reported receiving
      effective feedback were more likely to implement their LG than those reporting
      adequate feedback, 60.9 versus 37.9%, chi2(1) = 8.0, p = 0.01. CONCLUSIONS: SA is
      an essential part of goal setting and subsequent action. Perception of feedback
      plays a crucial role in LG implementation.

PMID- 29179636
TI  - Development and in vitro/in vivo evaluation of artemether and lumefantrine co
      loaded nanoliposomes for parenteral delivery.
AB  - Combination therapy of artemether (ART) and lumefantrine (LUM) is well
      established for the treatment of uncomplicated malaria worldwide. Nanoliposomes
      (NLs) encapsulating both drugs were prepared and freeze-dried. The lyophilized
      nanoliposomes exhibited high entrapment efficiency of artemether (66.18%),
      relatively low entrapment efficiency of lumefantrine (53.46%), low average size
      diameter (125.3 nm) and found to be stable at 4  degrees C for 60 days without
      significant change in mean particle diameter and drug entrapment efficiencies. In
      vitro drug release study has shown initial burst effect and then sustained
      release pattern over a time period of 30 h. In vivo toxicity study was examined
      by liver and kidney function test as well as histopathological examination.
      Nanoliposomes showed lower hemolytic potential (~10%) compared to all the
      components when studied individually. There was no significant change (p > 0.05)
      in biochemical parametes between control and treated group of animals.
      Pharmacokinetic data of ART + LUM NLs showed higher the area under the plasma
      concentration-time curve (AUC) values and prolonged residence time of drug in the
      blood circulation compared with ART + LUM solution. The tissue distribution
      demonstrated high uptake of ART + LUM-NLs in RES organs particularly in liver and
      spleen. Biocompatibility was confirmed by hepato- and nephrotoxicity analysis
      showed no sign of fibrosis, fatty infiltration, centrilobular necrosis and
      lymphocyte infiltration confirmed the suitability of developed formulation for
      treatment of malaria.

PMID- 29179638
TI  - The Hobnail Variant of Papillary Thyroid Carcinoma: Clinical/Molecular
      Characteristics of a Large Monocentric Series and Comparison with Conventional
      Histotypes.
AB  - BACKGROUND: The hobnail variant of papillary thyroid carcinoma (HPTC) has an
      aggressive behavior. The aims of this prospective study were to define the
      clinical/molecular characteristics of HPTC, and to compare them to those of
      conventional papillary thyroid carcinoma (PTC). METHODS: From 2010 to 2016, 25
      cases of HPTC, characterized clinically and molecularly (BRAF, RAS, TERT
      promoter, and TP53 mutations), were compared to a series of 165 consecutive cases
      of PTC. All patients underwent total thyroidectomy and received radioactive
      iodine treatment. Follow-up was available for 19 HPTC patients. RESULTS: Among
      the HPTC patients, 64% had a hobnail component >=30%, and 64% had multifocal
      disease. The mean tumor size was 30 mm; 96% of tumors were angio-invasive; 68%
      were N1, and 12% were M1; 58% harbored the BRAFV600E mutation, 12% had a mutation
      in the TERT promoter, 17% had a TP53 mutation, and not had a RAS mutation. At a
      mean follow-up of 39 months, 32% of patients had biochemical and/or structural
      disease. Tumor size was the only significant difference between patients with
      persistent disease and those with an excellent response (40 mm and 24 mm,
      respectively; p = 0.02). Compared to the PTC control group, the HPTC patients had
      larger tumors (30 mm vs. 16 mm; p < 0.001), more frequent lymph node involvement
      (68% vs. 38%; p = 0.01), and remote disease (16% vs. 3%; p < 0.0001), a similar
      prevalence of the BRAFV600E mutation (58% vs. 59%), a higher prevalence of TP53
      mutations (17% vs. 1%; p < 0.05), and a worse outcome (structural/biochemical
      disease: 32% vs. 9%; p < 0.0001). CONCLUSIONS: HPTC is an aggressive variant,
      characterized by large tumor size, lymph node involvement, a tendency to
      metastasize, and a worse outcome.

PMID- 29179637
TI  - Cone dystrophy and ectopic synaptogenesis in a Cacna1f loss of function model of
      congenital stationary night blindness (CSNB2A).
AB  - Congenital stationary night blindness 2A (CSNB2A) is an X-linked retinal
      disorder, characterized by phenotypically variable signs and symptoms of impaired
      vision. CSNB2A is due to mutations in CACNA1F, which codes for the pore-forming
      alpha1F subunit of a L-type voltage-gated calcium channel, Cav1.4. Mouse models
      of CSNB2A, used for characterizing the effects of various Cacna1f mutations, have
      revealed greater severity of defects than in human CSNB2A. Specifically, Cacna1f
      knockout mice show an apparent lack of visual function, gradual retinal
      degeneration, and disruption of photoreceptor synaptic terminals. Several reports
      have also noted cone-specific disruptions, including axonal abnormalities,
      dystrophy, and cell death. We have explored further the involvement of cones in
      our 'G305X' mouse model of CSNB2A, which has a premature truncation, loss-of
      function mutation in Cacna1f. We show that the expression of genes for several
      phototransduction-related cone markers is down-regulated, while that of several
      cellular stress- and damage-related markers is up-regulated; and that cone
      photoreceptor structure and photopic visual function - measured by
      immunohistochemistry, optokinetic response and electroretinography - deteriorate
      progressively with age. We also find that dystrophic cone axons establish synapse
      like contacts with rod bipolar cell dendrites, which they normally do not contact
      in wild-type retinas - ectopically, among rod cell bodies in the outer nuclear
      layer. These data support a role for Cav1.4 in cone synaptic development, cell
      viability, and synaptic transmission of cone-dependent visual signals. Although
      our novel finding of cone-to-rod-bipolar cell contacts in this mouse model of a
      retinal channelopathy may challenge current views of the role of Cav1.4 in
      photopic vision, it also suggests a potential new target for restorative therapy.

PMID- 29179639
TI  - Are neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and/or
      mean platelet volume (MPV) clinically useful as predictive parameters for
      preeclampsia?
AB  - OBJECTIVE: Preeclampsia (PE) is a severe pregnancy complication with significant
      maternal and neonatal morbi-mortality resulting in high health care costs.
      Prevention, mainly based on the administration of acetylsalicylic acid, is only
      possible if timely identification of high-risk patients can be realized in an
      easy, nonexpensive, and widely available method. This paper explores the clinical
      usability of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR),
      and/or mean platelet volume (MPV) in discriminating between women that will and
      those that will not develop PE. STUDY DESIGN: Demographic data and laboratory
      results were retrospectively collected and compared in 2050 pregnant women (164
      PE and 1886 controls) between 1 January 2014 and 31 January 2016. RESULTS: In the
      PE group, gravidity, parity, gestational age, and birth weight were significantly
      lower compared to the control group. Before the 20th pregnancy week, MPV was
      significantly elevated in the PE group compared to the controls (p = .006), hence
      analysis revealed an optimal cut-off point of 8.15 (sensitivity 66.7%,
      specificity 56.3%) for predicting PE. At the end of pregnancy, NLR and MPV
      appeared to be higher and PLR lower in the PE group compared to the controls,
      which strengthens the current knowledge on the pathogenesis of PE. CONCLUSIONS:
      MPV is significantly elevated in the first half of pregnancy in women who later
      develop PE and might therefore be implemented in combination with other
      parameters in a PE prediction model.

PMID- 29179640
TI  - 2,4-Dinitroanisole (DNAN) (2014).
AB  - 2,4-dinitroanisole (DNAN) is a warhead explosive currently under investigation as
      a replacement for TNT in melt-cast insensitive munitions. In animal studies, DNAN
      is a mild ocular and skin irritant with a significant potential for dermal
      absorption.  It is not a dermal sensitizer.  Acute and subacute rat inhalation
      studies demonstrated minimal toxicity with LC50 and LOAEL endpoints of 2.9 and
      150 mg/m3, respectively.  In rat oral toxicity studies (14 and 90 days) organ
      weight and clinical chemistry changes suggested hepatocellular injury and anemia,
      particularly in females.  In males there was evidence of testicular injury at the
      high-dose level (80 mg/kg/day).  The NOAELs for the 14- and 90-day studies were
      25 and 5 mg/kg/day, respectively, with a calculated BMDL10 value of 0.93
      mg/kg/day.  No chronic, carcinogenicity or reproductive/developmental toxicity
      data were available for DNAN, but a maternal and fetal NOAEL of 5.1 mg/kg/day was
      inferred.  DNAN is considered non-mutagenic and non-genotoxic.  It is metabolized
      in vivo to 2,4-dinitrophenol (DNP), but other details of its metabolism or
      pharmacokinetics are unknown.  There are considerable toxicity data for DNP, a
      known un-coupler of oxidative phosphorylation among other things, and these data
      may further inform regarding the safety of DNAN.  In humans, DNAN was a component
      of louse powder (prior to DDT) with no reported safety concerns.  However, its
      handling and use as a munition component presents a potential occupational hazard
      by both inhalation and dermal routes of exposure.  Considering both DNAN and DNP
      toxicity endpoints, the recommended Workplace Environmental Exposure limit for
      DNAN is 0.1 mg/m2 (8-h time weighted average).

PMID- 29179641
TI  - Microalgal process-monitoring based on high-selectivity spectroscopy tools:
      status and future perspectives.
AB  - Microalgae are well known for their ability to accumulate lipids intracellularly,
      which can be used for biofuels and mitigate CO2 emissions. However, due to
      economic challenges, microalgae bioprocesses have maneuvered towards the
      simultaneous production of food, feed, fuel, and various high-value chemicals in
      a biorefinery concept. On-line and in-line monitoring of macromolecules such as
      lipids, proteins, carbohydrates, and high-value pigments will be more critical to
      maintain product quality and consistency for downstream processing in a
      biorefinery to maintain and valorize these markets. The main contribution of this
      review is to present current and prospective advances of on-line and in-line
      process analytical technology (PAT), with high-selectivity - the capability of
      monitoring several analytes simultaneously - in the interest of improving product
      quality, productivity, and process automation of a microalgal biorefinery. The
      high-selectivity PAT under consideration are mid-infrared (MIR), near-infrared
      (NIR), and Raman vibrational spectroscopies. The current review contains a
      critical assessment of these technologies in the context of recent advances in
      software and hardware in order to move microalgae production towards process
      automation through multivariate process control (MVPC) and software sensors
      trained on "big data". The paper will also include a comprehensive overview of
      off-line implementations of vibrational spectroscopy in microalgal research as it
      pertains to spectral interpretation and process automation to aid and motivate
      development.

PMID- 29179642
TI  - A Follow-Up Strategy for Patients with an Excellent Response to Initial Therapy
      for Differentiated Thyroid Carcinoma: Less Is Better.
AB  - BACKGROUND: The risk of recurrence in patients with differentiated thyroid cancer
      (DTC) can be estimated based on their response to initial therapy. The aim of
      this study was to evaluate an adequate follow-up strategy for DTC patients with
      an excellent response by assessing the characteristics of structural recurrence.
      METHODS: This historical cohort study included 1359 DTC patients who had
      excellent response to total thyroidectomy with radioactive iodine remnant
      ablation. RESULTS: Among 1359 patients, 703 (54%) patients were classified as
      stage I according to the seventh tumor node metastasis staging system, and 987
      (73%) patients were classified as intermediate risk according to the American
      Thyroid Association's risk stratification after initial therapy. During a median
      of 8.7 years of follow-up, only 13 (1%) patients were confirmed to have
      structural recurrence. All of the recurrences were locoregional disease, and
      there were no distant metastases. Recurrences were detected late at a median of
      5.5 years after the initial surgery (range 3.6-10.7 years). All structural
      recurrences were detected on neck ultrasonography. Non-stimulated serum
      thyroglobulin (Tg) was detectable (>=0.2 ng/mL) in four (31%) patients, and serum
      anti-Tg antibodies were positive in one (8%) patient. However, non-stimulated
      serum Tg levels were stably low (<0.2 ng/mL) in eight (62%) patients when
      recurrences were detected. In addition to these 13 patients, 14 patients also
      presented with biochemical persistent disease at the end of follow-up.
      CONCLUSIONS: Recurrences of DTC in patients with an excellent response to initial
      therapy were detected relatively late. The intensity and frequency of follow-up
      of neck ultrasonography as well as serum Tg and anti-Tg antibody measurements
      should be reduced, especially within five years of the initial therapy, in DTC
      patients who have an excellent response.

PMID- 29179643
TI  - Sample size requirements for learning to classify with high-dimensional biomarker
      panels.
AB  - A common problem in biomedical research is to calculate the sample size required
      to learn a classifier using a (possibly high-dimensional) panel of biomarkers.
      This paper describes a simple method based on a Gaussian approximation for
      calculating the predictive performance of the learned classifier given the size
      of the biomarker panel, the size of the training sample, and the optimal
      predictive performance (expressed as C-statistic [Formula: see text]) of the
      biomarker panel that could be obtained if a training sample of unlimited size
      were available. Under the assumption that the biomarker effect sizes have the
      same correlation structure as the biomarkers, the required sample size does not
      depend upon these correlations, but only upon [Formula: see text] and upon the
      sparsity of the distribution of effect sizes, defined by the proportion of
      biomarkers that have nonzero effects. To learn a classifier that extracts 80% of
      the predictive information, the required case sample size varies from about 0.1
      cases per variable for a panel with [Formula: see text] and a sparse distribution
      of effect sizes (such that 1% of biomarkers have nonzero effect sizes) to nine
      cases per variable for a panel with [Formula: see text] and a diffuse
      distribution of effect sizes.

PMID- 29179644
TI  - Frequency and severity of potential drug interactions in a cohort of HIV-infected
      patients Identified through a Multidisciplinary team.
AB  - OBJECTIVES: Interactions between antiretroviral treatment (ART) and comedications
      are a concern in HIV-infected patients. This study aimed to determine the
      frequency and severity of potential drug-drug interactions (PDDIs) with ART in
      our setting. METHODS: Observational study by a multidisciplinary team in 1259
      consecutive HIV patients (March 2015-September 2016). Data on demographics, toxic
      habits, comorbidities, and current ART were collected. A structured questionnaire
      recorded concomitant medications (including occasional and over-the-counter
      drugs). PDDIs were classified into four categories: (1) no interactions, (2) mild
      (clinically non-significant), (3) moderate (requiring close monitoring or drug
      modification/dose adjustment), and (4) severe (contraindicated). STATISTICAL
      ANALYSIS: chi-square test, logistic regression analysis. RESULTS: In total, 881
      (70%) patients took comedication, and 563 (44.7%) had >= PDDI. Forty-one
      comedicated patients (4.6%) had severe and 522 (59.2%) moderate PDDIs. Moderate
      PDDIs mainly involved cardiovascular (53.8%) and central nervous system (40.2%)
      drugs. Independent risk factors for PDDIs were ART containing a boosted protease
      inhibitor (odds ratio [OR]=9.11, 95% confidence interval [CI] 5.15-16.11; p =
      0.0001) and/or non-nucleoside reverse transcriptase (NNRTI) (OR = 4.34, 95%CI
      2.49-7.55; p = 0.0001), HCV co-infection (OR = 3.26, 95%CI 2.15-4.93; p =
      0.0001), and use of two or more comedications (OR = 3.36, 95%CI 2.27-4.97; p =
      0.0001). Adherence and effectiveness of ART were similar in patients with and
      without PDDIs. The team made 133 recommendations related to comedications (drug
      change or dose adjustment) or ART (drug switch or change in administration
      schedule). CONCLUSIONS: Systematic evaluation detected a significant percentage
      of PDDIs requiring an intervention in HIV patients on ART. Monitoring and advice
      about drug-drug interactions should be part of routine practice.

PMID- 29179645
TI  - Efficient baseline utilization for incomplete block crossover clinical trials.
AB  - Incomplete block crossover trials with period-specific baseline and post-baseline
      (outcome) measures for each subject are often used in clinical drug development;
      without loss of generality, we focus on the three-treatment two-period ([Formula:
      see text]) crossover. Data from such trials are commonly analyzed using a mixed
      effects model with indicator terms for treatment and period, and an unstructured
      covariance matrix for the vector of intra-subject measurements. It is well-known
      that treatment effect estimates from this analysis are complex functions of both
      within-subject and between-subject treatment contrasts. We caution that the
      associated type I error rate and power for hypothesis testing can be non
      trivially influenced by how the baselines are utilized. Specifically, the mixed
      effects analysis which uses change from baseline as the dependent variable is
      shown to consistently underperform corresponding analyses in which the outcome is
      the dependent variable and linear combinations of the baselines are used as
      period-specific and/or period-invariant covariates. A simpler fixed effects
      analysis of covariance involving only within-subject contrasts is also described
      for small sample situations in which the mixed effects analyses can suffer from
      increased type I error rates. Theoretical insights, simulation results and an
      illustrative example with real data are used to develop the main points.

PMID- 29179646
TI  - Practical Initial Risk Stratification Based on Lymph Node Metastases in Pediatric
      and Adolescent Differentiated Thyroid Cancer.
AB  - BACKGROUND: Data on the risk stratification of pediatric differentiated thyroid
      cancer (DTC) remain scarce. This study aimed to evaluate the predictors of
      structural persistent/recurrent disease and revise an initial risk-stratification
      system in pediatric DTC patients. METHODS: This retrospective cohort study
      included 203 patients (aged <20 years) from two tertiary referral centers in
      Korea. The extent of cervical lymph node (LN) metastasis was classified based on
      the location or number of metastatic LNs. RESULTS: During a median follow-up
      duration of 5.5 years, structural persistent/recurrent disease was observed in 51
      (25%) patients, including 22 (11%) with distant metastases. The presence of
      extrathyroidal extension (ETE) and lateral cervical LN metastases or more than
      five metastatic LNs were independent predictors for structural
      persistent/recurrent disease. The presence of bilateral lateral cervical LN
      metastases or >10 metastatic LNs were independent predictors for distant
      metastasis. A total of 67 (33%), 72 (35%), and 64 (32%) patients were classified
      into the low-, intermediate-, and high-risk groups, respectively, based on the
      presence of ETE and the extent of cervical LN metastases. Compared to the low
      risk group, the intermediate- and high-risk groups had a significantly greater
      risk of structural persistent/recurrent disease (hazard ratio = 7.32, p = 0.008,
      and hazard ratio = 24.28, p < 0.001, respectively). CONCLUSIONS: This revised
      initial risk-stratification system based on the presence of ETE and the extent of
      cervical LN metastasis is useful for predicting the clinical outcomes of
      pediatric DTC patients. The findings could facilitate the practical use of a risk
      stratification system.

PMID- 29179647
TI  - Efficacy of group psychotherapy for posttraumatic stress disorder: Systematic
      review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The present meta-analysis evaluates the efficacy of group
      psychotherapy for post-traumatic stress disorder (PTSD) in adults directly
      compared to no treatment or active treatments examined in randomized controlled
      trials (RCTs). METHOD: Electronic databases were searched for eligible studies.
      Effects on PTSD symptoms, depression, and anxiety were extracted. Between- and
      within-group effect sizes (Hedges' g) were calculated using a random-effects
      model. Data were adjusted to account for dependencies among observations in
      groups. RESULTS: Twenty RCTs were included comprising 2244 individuals. Results
      showed significant effects of group psychotherapy in reducing symptoms of PTSD
      compared to no-treatment control groups (k = 13; g = 0.70; 95% CI: 0.41; 0.99).
      No significant differences in efficacy were found between group psychotherapy and
      other active treatments (k = 8; g = 0.13; 95% CI: -0.16; 0.42). Moderator
      analyses confirmed gender and trauma type as important moderators of within
      treatment effects for PTSD. CONCLUSIONS: Group treatments are associated with
      improvements in symptoms of PTSD. Particularly, the efficacy of exposure-based
      cognitive-behavioral group therapy (group CBT) is empirically well demonstrated.
      Still little is known about the effects of group treatment approaches other than
      CBT and the comparative efficacy to alternative treatments such as individual
      therapy or pharmacotherapy.

PMID- 29179648
TI  - Sex Differences in Thermal, Stress, and Inflammatory Responses to Minocycline
      Administration in Rats with Traumatic Brain Injury.
AB  - Persistent inflammation, mediated in part by increases in cytokines, is a
      hallmark of traumatlc brain injury (TBI). Minocycline has been shown to inhibit
      post-TBI neuroinflammation in male rats and mice, but has not been tested in
      females. Here, we studied sex differences in thermal, stress, and inflammatory
      responses to TBI and minocycline. Female rats were ovariectomized under
      isoflurane anesthesia at 33-36 days of age. At 45-55 days of age, male and female
      rats were implanted intraperitoneally (i.p.) with calibrated transmitters for
      monitoring body temperature. Moderate cortical contusion injury (CCI) or sham
      surgery was performed when the rats attained 60-70 days of age. One hour after
      surgery, rats were injected i.p. with minocycline (50 mg/kg) or saline (0.3 mL);
      injections were repeated once daily for the next 3 days. At 28 days after CCI or
      sham surgery, 30 min restraint stress was initiated and blood samples were
      obtained by tail venipuncture before the onset of restraint and at 30, 60, and 90
      min after stress onset. At 35 days after CCI or sham surgery, rats were
      decapitated and blood was collected for corticosterone (CORT) and cytokine
      analysis. The brains were removed and ipsilateral cortical tissue and hippocampus
      were dissected and subsequently assayed for interleukin (IL)-1beta, IL-6, and
      tumor necrosis factor (TNF)-alpha. Hyperthermia occurred during days 1-6 post-CCI
      in male rats, but only on the day of CCI in female rats, and minocycline
      prevented its occurrence in both sexes. Minocycline facilitated suppression of
      the CORT response to restraint stress in both sexes. In females, but not males,
      hippocampal IL-6 content increased post-CCI compared with sham-injured controls,
      whereas IL-1beta content was augmented by minocycline. Hippocampal TNF-alpha was
      unaffected by CCI and minocycline. These results demonstrate sex differences in
      immediate thermal and long-lasting stress and cytokine responses to CCI, and only
      short-term protective effects of minocycline on hyperthermia.

PMID- 29179649
TI  - Mesenchymal Stem Cells for Frailty?
AB  - Frailty is a medical syndrome associated with advancing age characterized by
      reduced functional reserve, strength, endurance, and susceptibility to infection
      associated with high morbidity, hospitalization, and death. Nonspecific
      interventions to improve the healthspan of affected patients include physical
      therapy, exercise, improved nutrition, etc. Among the hallmarks of aging,
      depletion of stem cells with resultant compromise of regeneration and repair of
      tissues informs a rational stem cell-based replacement strategy. This hypothesis
      has been evaluated in a randomized, double-blind, placebo-controlled clinical
      trial utilizing human allogeneic mesenchymal stem cells (allo-hMSCs), a facile,
      scalable stem cell replacement therapy. Intravenous infusion of 100 or 200
      million allo-hMSCs was deemed safe in aged frail individuals. However, modest
      improvement outcomes were limited to the lower dose, a finding that remains
      difficult to explain. Future studies are definitely warranted given the magnitude
      of this increasingly important medical syndrome.

PMID- 29179650
TI  - Statin related adverse effects and patient education: a study from resource
      limited settings.
AB  - BACKGROUND: Statins are the most widely prescribed class of drugs for coronary
      artery disease (CAD) patients and yet literature on the prevalence of statin
      related adverse effects (AEs) and gaps in patient education is quite limited
      especially in resource-limited settings of developing world. OBJECTIVES: The
      present study was conducted to determine the prevalence of myopathy (muscle
      ailments) and other statin associated adverse effects among CAD patients on
      statin therapy. The study also aimed to assess patient perceptions, attitudes and
      awareness concerning the use of statins. METHODS: It was a cross-sectional study
      conducted among 300 adult CAD patients visiting the out-patient department of a
      tertiary care hospital in North India, who were receiving statins for their
      diagnosis. An interviewer administered questionnaire was used to collect data on
      statin use among patients and adverse effects experienced. RESULTS: Myopathy or
      muscle related ailments like muscle pain, cramps and muscle weakness were the
      most prevalent (32, 34 and 47%, respectively), followed by numbness, tingling and
      burning in the extremities (31%). Joint pain and cognitive impairments were seen
      in nearly 20% of the patients. The level of awareness among participants
      regarding the use of statins was sub-optimal. Lack of knowledge and under
      reporting of adverse effects were major concerns. CONCLUSION: The study shows
      that a considerable proportion of statin users experience adverse effects and
      knowledge and awareness amongst patients is inadequate. Awareness programmes and
      counselling for patients, sensitisation of healthcare professionals and better
      screening systems for monitoring AEs can help improve the scenario.

PMID- 29179651
TI  - Endovascular Therapy of the Superficial Femoral Artery Via a Stand-Alone
      Transradial Access: A Single-Center Experience.
AB  - OBJECTIVE: We describe our experience in transradial recanalization of the
      superficial femoral artery (SFA), and we provide a stepwise approach accounting
      for the patient's height and optimizing the yield of currently available devices.
      METHODS AND RESULTS: Fifteen patients with simple SFA disease, including 4
      patients with total SFA occlusions <15 cm, were selected for stand-alone
      transradial recanalization. A 6F, 125-cm multipurpose guiding catheter was used
      to cannulate the limb of interest and support device delivery. The procedure was
      successful in all patients and consisted of balloon angioplasty (using 0.014",
      200-cm shaft monorail balloons) in all patients, and orbital atherectomy in 6
      patients. We illustrate the steps and challenges of the transradial approach,
      namely the limited support in complex disease and the limited reach of current
      equipment. CONCLUSION: In patients with simple SFA disease, transradial
      recanalization appears feasible and safe but currently limited to balloon
      angioplasty +/- orbital atherectomy. Proximal SFA stenting may be feasible in
      patients <160 cm in height.

PMID- 29179652
TI  - The effectiveness of an occlusal disclosure sheet to diagnose sleep bruxism: A
      pilot study.
AB  - Objective To evaluate the utility of vacuum-pressed, BruxChecker(r) sheets for
      the diagnosis of sleep bruxism. Methods Twenty subjects participated in this
      study. Tooth contact during sleep was recorded using a 0.1 mm-thick polyvinyl
      chloride sheet called BruxChecker(r). The area of the BruxChecker(r) in which the
      red dye was removed was measured. In addition, the EMG activity of the masseter
      muscle during sleep was recorded. The numbers of bruxism bursts and episodes were
      counted, and their correlations with the peeled area of the red dye on the
      BruxChecker(r) were evaluated. Results The number of bruxism bursts and
      episodes/hr significantly correlated with the peeled area at all cut-off values.
      The peeled area significantly correlated with the number of phasic type bruxism
      episodes but not with tonic or mixed type bruxism episodes. Discussion Since the
      BruxChecker(r) peeled area reflected phasic type sleep bruxism, the sheets may be
      useful in sleep bruxism screening.

PMID- 29179653
TI  - Walk this way: validity evidence of iphone health application step count in
      laboratory and free-living conditions.
AB  - Several attempts have been made to demonstrate the accuracy of the iPhone
      pedometer function in laboratory test conditions. However, no studies have
      attempted to evaluate evidence of convergent validity of the iPhone step counts
      as a surveillance tool in the field. This study takes a pragmatic approach to
      evaluating Health application derived iPhone step counts by measuring accuracy of
      a standardized criterion iPhone SE and a heterogeneous sample of participant
      owned iPhones (6 or newer) in a laboratory condition, as well as comparing
      personal iPhones to accelerometer derived steps in a free-living test. During lab
      tests, criterion and personal iPhones differed from manually counted steps by a
      mean bias of less than +/-5% when walking at 5km/h, 7.5km/h and 10km/h on a
      treadmill, which is generally considered acceptable for pedometers. In the free
      living condition steps differed by a mean bias of 21.5% or 1340 steps/day when
      averaged across observation days. Researchers should be cautioned in considering
      the use of iPhone models as a research grade pedometer for physical activity
      surveillance or evaluation, likely due to the iPhone not being continually
      carried by participants; if compliance can be maximized then the iPhone might be
      suitable.

PMID- 29179654
TI  - Futility for subgroup analyses in the adaptive signature design.
AB  - Subgroup analyses in clinical trials are becoming increasingly important. In
      cancer research, more and more targeted therapies are explored from which
      probably only a portion of the whole population will benefit. An adaptive design
      for subgroup selection with identification of a subgroup, the adaptive signature
      design, was proposed in the literature. Unfortunately, measuring and validating
      the variables defining the subgroup (i.e. biomarkers) can be extremely expensive.
      For this reason, we propose an extension of this design where subgroup analysis
      is not performed when the overall results suggest that it is unlikely to achieve
      statistical significance in the subgroup. Avoiding measuring and validating
      expensive biomarkers in this case can save resources that could be used on more
      promising research.

PMID- 29179655
TI  - Robust inference under the beta regression model with application to health care
      studies.
AB  - Data on rates, percentages, or proportions arise frequently in many different
      applied disciplines like medical biology, health care, psychology, and several
      others. In this paper, we develop a robust inference procedure for the beta
      regression model, which is used to describe such response variables taking values
      in (0, 1) through some related explanatory variables. In relation to the beta
      regression model, the issue of robustness has been largely ignored in the
      literature so far. The existing maximum likelihood-based inference has serious
      lack of robustness against outliers in data and generate drastically different
      (erroneous) inference in the presence of data contamination. Here, we develop the
      robust minimum density power divergence estimator and a class of robust Wald-type
      tests for the beta regression model along with several applications. We derive
      their asymptotic properties and describe their robustness theoretically through
      the influence function analyses. Finite sample performances of the proposed
      estimators and tests are examined through suitable simulation studies and real
      data applications in the context of health care and psychology. Although we
      primarily focus on the beta regression models with a fixed dispersion parameter,
      some indications are also provided for extension to the variable dispersion beta
      regression models with an application.

PMID- 29179656
TI  - End-to-side neurotization with the phrenic nerve in restoring the function of toe
      extension: an experimental study in a rat model.
AB  - The phrenic nerve being transferred to the posterior division of the lower trunk
      with end-to-end neurorrhaphy is reported to be effective in restoring the
      function of digit extension in literature. However, the phrenic nerve is
      extremely important in respiration. We designed an animal experiment to discover
      whether the phrenic nerve being transferred to the posterior division of the
      lower trunk with end-to-side neurotization was feasible and provided the
      theoretical basis. A sum of 36 Sprague-Dawley rats was randomly assigned to one
      of two groups. In Group A, the phrenic nerve was transferred to the posterior
      division of the lower trunk with end-to-side neurotization. In Group B, the
      posterior division of the lower trunk was directly sutured. The results of
      behavioral assessment, electrophysiology, histology and nerve fiber count and
      muscle weight at 12 weeks postoperatively were recorded. In Group A, none of the
      rats experienced tachypnea. The motion of slight toe extension was observed. The
      results of electrophysiology, histology and nerve fiber count and muscle weight
      in Group A were not as well as those of Group B, but gradually improved with
      time. The phrenic nerve being transferred to the posterior division of lower
      trunk with end-to-side neurotization can partially restore the function of toe
      extension in a rat model. Whether the function of digit extension can be restored
      by the phrenic nerve with end-to-side neurotization in humans still needs more
      practice in clinic.

PMID- 29179657
TI  - Psychosocial factors predicting risky sexual behaviour among long distance truck
      drivers in Lagos, Nigeria.
AB  - Long distance truck drivers (LDTDs) have been identified as one of the groups at
      higher risk for human immunodeficiency virus (HIV) infection. Understanding how
      certain social and psychological variables that have a strong theoretical basis
      contribute to sexual risk behaviour will guide in the implementation process of
      HIV risk-reduction intervention in the trucking population. In line with the
      conceptualisation of Information, Motivation and Behavioural skills model, we
      examined the extent that HIV knowledge, attitude towards condom use, peer support
      to condom use, perceived vulnerability to HIV/AIDS, and condom use self-efficacy
      will independently and jointly explain sexual risk behaviours of LDTDs in a
      haulage company in Lagos, Nigeria. A cross-sectional survey design was used and
      154 drivers with ages ranging from 27 to 68 years (M = 44.03, SD = 8.82)
      completed copies of a questionnaire comprising demographics and measures of
      psychological variables. Psychological factors that included HIV knowledge,
      attitude towards condom use, perceived vulnerability to HIV/AIDS, peer support to
      condom use, and condom use self-efficacy significantly jointly predicted sexual
      risk behaviours (R2 = .59, F(5, 148) = 42.63; p < .05), by accounting for about
      59% of the explained variance in sexual risk behaviours. Social factors that
      included age, number of years of education, number of wives, number of
      intercourses in the last three months, number of partners apart from primary
      partners, and number of weeks spent outside home significantly jointly predicted
      sexual risk behaviour (R2 = .15, F(6, 147) = 4.39; p < .05) by accounting for
      about 15% of the explained variance in sexual risk behaviour among the drivers.
      It is concluded that all the psychological and social factors examined as
      predictor variables could jointly play important roles in prevention intervention
      programmes for reducing sexual risk behaviours of LDTDs. Stakeholders should
      sensitise LDTDs on the need to realise that they are a high-risk group and are
      more vulnerable to HIV infection; thus, behaviour change is indispensable in
      their sexual relationships.

PMID- 29179658
TI  - Short- and long-term effects of divorce and separation on housing tenure in
      England and Wales.
AB  - This paper investigates the effects of marital and non-marital separation on
      individuals' housing tenure in England and Wales. We apply competing risks event
      history models to data from the British Household Panel Survey and the UK
      Household Longitudinal Study to analyse the risk of a residential move to
      different tenure types, for single, married, cohabiting, and separated men and
      women. Separated individuals are more likely to move and experience a tenure
      change than those who are single or in a relationship. Among separated people,
      private renting is the most common outcome of a move; however, women are also
      likely to move to social renting, whereas men tend to move to homeownership. This
      pattern persists when we account for time since separation and order of move,
      indicating a potential long-term effect of separation on housing tenure. This
      long-term effect is especially pertinent to separated women who cannot afford
      homeownership.

PMID- 29179659
TI  - DYRK1A Is a Regulator of S-Phase Entry in Hepatic Progenitor Cells.
AB  - Hepatic progenitor cells (HPCs) are adult liver stem cells that act as second
      line of defense in liver regeneration. They are normally quiescent, but in case
      of severe liver damage, HPC proliferation is triggered by external activation
      mechanisms from their niche. Although several important proproliferative
      mechanisms have been described, it is not known which key intracellular
      regulators govern the switch between HPC quiescence and active cell cycle. We
      performed a high-throughput kinome small interfering RNA (siRNA) screen in HepaRG
      cells, a HPC-like cell line, and evaluated the effect on proliferation with a 5
      ethynyl-2'-deoxyuridine (EdU) incorporation assay. One hit increased the
      percentage of EdU-positive cells after knockdown: dual specificity tyrosine
      phosphorylation regulated kinase 1A (DYRK1A). Although upon DYRK1A silencing, the
      percentage of EdU- and phosphorylated histone H3 (pH3)-positive cells was
      increased, and total cell numbers were not increased, possibly through a
      subsequent delay in cell cycle progression. This phenotype was confirmed with
      chemical inhibition of DYRK1A using harmine and with primary HPCs cultured as
      liver organoids. DYRK1A inhibition impaired Dimerization Partner, RB-like, E2F,
      and multivulva class B (DREAM) complex formation in HPCs and abolished its
      transcriptional repression on cell cycle progression. To further analyze DYRK1A
      function in HPC proliferation, liver organoid cultures were established from
      mBACtgDyrk1A mice, which harbor one extra copy of the murine Dyrk1a gene
      (Dyrk+++). Dyrk+++ organoids had both a reduced percentage of EdU-positive cells
      and reduced proliferation compared with wild-type organoids. This study provides
      evidence for an essential role of DYRK1A as balanced regulator of S-phase entry
      in HPCs. An exact gene dosage is crucial, as both DYRK1A deficiency and
      overexpression affect HPC cell cycle progression.

PMID- 29179660
TI  - Teaching resident physicians the power of implicit bias and how it impacts
      patient care utilizing patients who have experienced incarceration as a model.
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 of 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- 29179661
TI  - Psychoactive substance use in specialized psychiatric care patients.
AB  - Objective Life expectancy of psychiatric patients is markedly shorter compared to
      the general population, likely partly due to smoking or misuse of other
      substances. We investigated prevalence and correlates of substance use among
      psychiatric patients. Methods Within the Helsinki University Psychiatric
      Consortium Study, data were collected on substance use (alcohol, smoking, and
      illicit drugs) among patients with schizophrenia or schizoaffective disorder (n =
      113), bipolar (n = 99), or depressive disorder (n = 188). Clinical diagnoses of
      substance use were recorded, and information on smoking, hazardous alcohol use,
      or misuse of other substances was obtained using questionnaires. Results One
      fourth (27.7%) of the patients had clinical diagnoses of substance use disorders.
      In addition, in the Alcohol Use Disorders Identification Test, 43.1% had
      hazardous alcohol use and 38.4% were daily smokers. All substance use was more
      common in men than in women. Bipolar patients had the highest prevalence of
      alcohol use disorders and hazardous use, whereas those with schizophrenia or
      schizoaffective disorder were more often daily smokers. In regression analyses,
      self-reported alcohol consumption was associated with symptoms of anxiety and
      borderline personality disorder and low conscientiousness. No associations
      emerged for smoking. Conclusions The vast majority of psychiatric care patients
      have a diagnosed substance use disorder, hazardous alcohol use, or smoke daily,
      males more often than females. Bipolar patients have the highest rates of alcohol
      misuse, schizophrenia or schizoaffective disorder patients of smoking. Alcohol
      use may associate with symptoms of anxiety, borderline personality disorder, and
      low conscientiousness. Preventive and treatment efforts specifically targeted at
      harmful substance use among psychiatric patients are necessary.

PMID- 29179662
TI  - Patient experience with healthcare services among older adults with serious
      mental illness compared to the general older population.
AB  - Objective To compare patient experience with healthcare services and providers
      among older patients (>=50 years old) with and without serious mental illness.
      Methods Using secondary data from the Medical Expenditures Panel Survey from 2003
      through 2013, we compared adults aged 50 years and older with schizophrenia
      spectrum disorder ( n = 106), mood disorders (i.e., major depressive disorder and
      bipolar disorder) ( n = 419), and no serious mental illness ( n = 34,921).
      Results Older adults with schizophrenia spectrum disorder reported significantly
      worse provider communication than older adults without serious mental illness.
      Older adults with mood disorders reported the greatest barriers to shared
      decision-making and the greatest difficulty accessing services. Conclusions Our
      results highlight the need to improve the patient experience of older adults with
      serious mental illness. Addressing provider communication, shared decision
      making, and access to care among this vulnerable group of older adults may impact
      clinical outcomes and costs. Future research examining the extent to which
      improving the patient experience may improve health outcomes and enhance
      treatment for this highly vulnerable older group is warranted.

PMID- 29179663
TI  - Balint group leadership: Conceptual foundations and a framework for leadership
      development?
AB  - This article is based on a talk given at the International Balint Federation
      leadership congress in Warsaw (September 2016). It explores the conceptual
      foundations of Balint group leadership and starts by emphasizing the mutuality
      between psychoanalysts and medical practitioners working together. The parallel
      process between consulting room and group, and subsequently from group back to
      the consulting room, is delineated as the central construct in understanding the
      role of the leader. Having proposed a conceptual model for thinking about
      leadership interventions, the article discusses developments in some contemporary
      approaches to leadership: coleadership, the use of role play, psychodrama,
      pushback, and morale. It concludes by introducing Keats' notion of negative
      capability as a way of thinking about creativity in Balint group leadership.

PMID- 29179664
TI  - Incorporating peer support during in vivo exposure to reverse dropout from
      prolonged exposure therapy for posttraumatic stress disorder: Clinical outcomes.
AB  - Objective Prolonged exposure is characterized by reported dropout rates ranging
      from 25% to 40%. This premature attrition is also observed in other evidence
      based treatments for posttraumatic stress disorder. While home-based telehealth
      delivery of prolonged exposure resolves logistical barriers to care such as
      travel time and cost, dropout appears unaffected. A previous study on dropouts
      from prolonged exposure delivered via telehealth found that Veterans,
      particularly those receiving care via telehealth, reported problems with in vivo
      exposure and that having a peer to offer support during in vivo exposure
      assignments might have prevented their attrition from treatment. Methods The
      present pilot study treatment was designed in a manner consistent with the
      aforementioned Veteran suggestions, specifically to involve peers offering verbal
      support and encouragement during in vivo exposure homework. Such a treatment
      modification might be particularly useful for those receiving care via
      telehealth, given increased difficulties with exposure reported when this
      treatment delivery modality is used. It was hypothesized that dropouts would
      agree to reengage in treatment with a peer and would subsequently evince
      improvement in posttraumatic stress disorder and depression scores as a result of
      this treatment reengagement. Results Of 82 dropouts from prolonged exposure, 29
      reentered treatment when offered peer support during exposure (12 in telehealth
      and 17 in person). Conclusion Treatment reentry was effective insofar as indices
      of both posttraumatic stress disorder and depression were significantly reduced
      in both telehealth and in person groups, indicating that using peers in this way
      may be an effective means by which to return Veterans to care, and ultimately
      reduce symptomatology.

PMID- 29179665
TI  - Effect size calculation in meta-analyses of psychotherapy outcome research.
AB  - Meta-analysis of psychotherapy intervention research normally examines
      differences between treatment groups and some form of comparison group (e.g.,
      wait list control; alternative treatment group). The effect of treatment is
      normally quantified as a standardized mean difference (SMD). We describe
      procedures for computing unbiased estimates of the population SMD from sample
      data (e.g., group Ms and SDs), and provide guidance about a number of
      complications that may arise related to effect size computation. These
      complications include (a) incomplete data in research reports; (b) use of
      baseline data in computing SMDs and estimating the population standard deviation
      (sigma); (c) combining effect size data from studies using different research
      designs; and (d) appropriate techniques for analysis of data from studies
      providing multiple estimates of the effect of interest (i.e., dependent effect
      sizes). Clinical or Methodological Significance of this article: Meta-analysis is
      a set of techniques for producing valid summaries of existing research. The
      initial computational step for meta-analyses of research on intervention outcomes
      involves computing an effect size quantifying the change attributable to the
      intervention. We discuss common issues in the computation of effect sizes and
      provide recommended procedures to address them.

PMID- 29179666
TI  - The inflammatory response to stress and angiogenesis in liver resection for
      colorectal liver metastases: a randomized controlled trial comparing open versus
      laparoscopic approach.
AB  - BACKGROUND: This study evaluates the surgical stress response following
      laparoscopic and open liver resection for colorectal liver metastasis (CRLM).
      METHODS: Patients with CRLM were prospectively randomized to receive open or
      laparoscopic liver resection (NCT03131778). Blood samples were drawn
      preoperatively and 24 h after resection. The serum interleukin-6 (IL-6) and IL-8
      levels were measured. Furthermore, the mRNA levels of angiogenesis-related
      factors (vascular endothelial growth factor [VEGF] and HIF-1) and inflammation
      related factors (COX-2 and MMP-9) in both tumor tissue and normal liver
      parenchyma were detected. RESULTS: Twenty patients for each arm were included.
      Size of metastasis, type of resection, and neoadjuvant therapy were comparable
      between groups. Postoperative stay was shorter in the laparoscopic group. Higher
      levels of IL-6 were observed after the operation in both open and laparoscopic
      groups, although no differences in the post-operative levels between the groups
      was noted. Similarly, there were no significant differences in the mRNA
      expression of VEGF, HIF-1, MMP-9, and COX-2 between the treatment groups. No
      differences were observed in terms of overall survival and disease free survival.
      CONCLUSIONS: The immunological effects of treatment were similar between the
      groups. Thus, the laparoscopic approach does not seem to significantly influence
      the surgical stress and tumor related factors in patients suffering from
      colorectal liver metastases.

PMID- 29179668
TI  - Midwest Nursing Research Society News.

PMID- 29179667
TI  - High-Fidelity Measures of Whole-Brain Functional Connectivity and White Matter
      Integrity Mediate Relationships between Traumatic Brain Injury and Post-Traumatic
      Stress Disorder Symptoms.
AB  - Traumatic brain injury (TBI) disrupts brain communication and increases risk for
      post-traumatic stress disorder (PTSD). However, mechanisms by which TBI-related
      disruption of brain communication confers PTSD risk have not been successfully
      elucidated in humans. This may be in part because functional MRI (fMRI), the most
      common technique for measuring functional brain communication, is unreliable for
      characterizing individual patients. However, this unreliability can be overcome
      with sufficient within-individual data. Here, we examined whether relationships
      could be observed among TBI, structural and functional brain connectivity, and
      PTSD severity by collecting ~3.5 hours of resting-state fMRI and diffusion tensor
      imaging (DTI) data in each of 26 United States military veterans. We observed
      that a TBI history was associated with decreased whole-brain resting-state
      functional connectivity (RSFC), while the number of lifetime TBIs was associated
      with reduced whole-brain fractional anisotropy (FA). Both RSFC and FA explained
      independent variance in PTSD severity, with RSFC mediating the TBI-PTSD
      relationship. Finally, we showed that large amounts of per-individual data
      produced highly reliable RSFC measures, and that relationships among TBI,
      RSFC/FA, and PTSD could not be observed with typical data quantities. These
      results demonstrate links among TBI, brain connectivity, and PTSD severity, and
      illustrate the need for precise characterization of individual patients using
      high-data fMRI scanning.

PMID- 29179669
TI  - In Situ Activation and Preservation of Penile Progenitor Cells Using Icariside II
      in an Obesity-Associated Erectile Dysfunction Rat Model.
AB  - Obesity-associated erectile dysfunction (ED) involves pathologic change that may
      be related to deficit of the penile endogenous stem/progenitor cells. Therefore,
      an in-depth study of the penile stem/progenitor cells in the pathogenesis of ED
      is warranted. For this study, eight Zucker Lean (ZUC-Leprfa 186; ZL group) and 16
      Zucker Fatty (ZUC-Leprfa 185; ZF) male rats received an intraperitoneal injection
      of 5-ethynyl-2-deoxyuridine (EdU) to track endogenous stem cells. Twelve weeks
      later, the ZF rats were randomized to gavage feeding with 1.5 mg/kg/day of
      icariside II (ZF + ICA II group) or the solvent (ZF group). Treatment lasted 4
      weeks and was followed by a 1-week washout period. ZF rats had impaired erectile
      function with related pathologic changes compared with ZL rats. ICA II treatment
      restored erectile function and prevented smooth muscle atrophy, endothelial
      dysfunction, and lipid accumulation compared with no treatment. EdU label
      retaining cell levels were higher in the ZF + ICA II group compared with the ZF
      group. Histone 3 phosphorylation at Ser 10, a specific mitotic cell marker, was
      additionally used to identify dividing cells. ICA II activated more penile stem
      cells to proliferate in ZF rats compared with ZL rats. These results suggest that
      ZF rats can be used as a model for obesity-associated ED and that ICA II improves
      erectile function and pathologic changes through endogenous progenitor cell
      preservation and proliferation.

PMID- 29179670
TI  - Detecting transitions in protein dynamics using a recurrence quantification
      analysis based bootstrap method.
AB  - BACKGROUND: Proteins undergo conformational transitions over different time
      scales. These transitions are closely intertwined with the protein's function.
      Numerous standard techniques such as principal component analysis are used to
      detect these transitions in molecular dynamics simulations. In this work, we add
      a new method that has the ability to detect transitions in dynamics based on the
      recurrences in the dynamical system. It combines bootstrapping and recurrence
      quantification analysis. We start from the assumption that a protein has a
      "baseline" recurrence structure over a given period of time. Any statistically
      significant deviation from this recurrence structure, as inferred from complexity
      measures provided by recurrence quantification analysis, is considered a
      transition in the dynamics of the protein. RESULTS: We apply this technique to a
      132 ns long molecular dynamics simulation of the beta-Lactamase Inhibitory
      Protein BLIP. We are able to detect conformational transitions in the nanosecond
      range in the recurrence dynamics of the BLIP protein during the simulation. The
      results compare favorably to those extracted using the principal component
      analysis technique. CONCLUSIONS: The recurrence quantification analysis based
      bootstrap technique is able to detect transitions between different dynamics
      states for a protein over different time scales. It is not limited to linear
      dynamics regimes, and can be generalized to any time scale. It also has the
      potential to be used to cluster frames in molecular dynamics trajectories
      according to the nature of their recurrence dynamics. One shortcoming for this
      method is the need to have large enough time windows to insure good statistical
      quality for the recurrence complexity measures needed to detect the transitions.

PMID- 29179671
TI  - Phylogenomics of Cas4 family nucleases.
AB  - BACKGROUND: The Cas4 family endonuclease is a component of the adaptation module
      in many variants of CRISPR-Cas adaptive immunity systems. Unlike most of the
      other Cas proteins, Cas4 is often encoded outside CRISPR-cas loci (solo-Cas4) and
      is also found in mobile genetic elements (MGE-Cas4). RESULTS: As part of our
      ongoing investigation of CRISPR-Cas evolution, we explored the phylogenomics of
      the Cas4 family. About 90% of the archaeal genomes encode Cas4 compared to only
      about 20% of the bacterial genomes. Many archaea encode both the CRISPR
      associated form (CAS-Cas4) and solo-Cas4, whereas in bacteria, this combination
      is extremely rare. The solo-cas4 genes are over-represented in environmental
      bacteria and archaea with small genomes that typically lack CRISPR-Cas,
      suggesting that Cas4 could perform uncharacterized defense or repair functions in
      these microbes. Phylogenomic analysis indicates that both the CRISPR-associated
      cas4 genes are often transferred horizontally but almost exclusively, as part of
      the adaptation module. The evolutionary integrity of the adaptation module
      sharply contrasts the rampant shuffling of CRISPR-cas modules whereby a given
      variant of the adaptation module can combine with virtually any effector module.
      The solo-cas4 genes evolve primarily via vertical inheritance and are subject
      only to occasional horizontal transfer. The selection pressure on cas4 genes does
      not substantially differ between CAS-Cas4 and solo-cas4, and is close to the
      genomic median. Thus, cas4 genes, similarly to cas1 and cas2, evolve similarly to
      'regular' microbial genes involved in various cellular functions, showing no
      evidence of direct involvement in virus-host arms races. A notable feature of the
      Cas4 family evolution is the frequent recruitment of cas4 genes by various mobile
      genetic elements (MGE), particularly, archaeal viruses. The functions of Cas4 in
      these elements are unknown and potentially might involve anti-defense roles.
      CONCLUSIONS: Unlike most of the other Cas proteins, Cas4 family members are as
      often encoded by stand-alone genes as they are incorporated in CRISPR-Cas
      systems. In addition, cas4 genes were repeatedly recruited by MGE, perhaps, for
      anti-defense functions. Experimental characterization of the solo and MGE-encoded
      Cas4 nucleases is expected to reveal currently uncharacterized defense and anti
      defense systems and their interactions with CRISPR-Cas systems.

PMID- 29179672
TI  - An efficient error correction algorithm using FM-index.
AB  - BACKGROUND: High-throughput sequencing offers higher throughput and lower cost
      for sequencing a genome. However, sequencing errors, including mismatches and
      indels, may be produced during sequencing. Because, errors may reduce the
      accuracy of subsequent de novo assembly, error correction is necessary prior to
      assembly. However, existing correction methods still face trade-offs among
      correction power, accuracy, and speed. RESULTS: We develop a novel overlap-based
      error correction algorithm using FM-index (called FMOE). FMOE first identifies
      overlapping reads by aligning a query read simultaneously against multiple reads
      compressed by FM-index. Subsequently, sequencing errors are corrected by k-mer
      voting from overlapping reads only. The experimental results indicate that FMOE
      has highest correction power with comparable accuracy and speed. Our algorithm
      performs better in long-read than short-read datasets when compared with others.
      The assembly results indicated different algorithms has its own strength and
      weakness, whereas FMOE is good for long or good-quality reads. CONCLUSIONS: FMOE
      is freely available at https://github.com/ythuang0522/FMOC .

PMID- 29179673
TI  - Quantitative trait locus mapping of Populus bark features and stem diameter.
AB  - BACKGROUND: Bark plays important roles in photosynthate transport and storage,
      along with physical and chemical protection. Bark texture varies extensively
      among species, from smooth to fissured to deeply furrowed, but its genetic
      control is unknown. This study sought to determine the main genomic regions
      associated with natural variation in bark features and stem diameter.
      Quantitative trait loci (QTL) were mapped using an interspecific pseudo-backcross
      pedigree (Populus trichocarpa x P. deltoides and P. deltoides) for bark texture,
      bark thickness and diameter collected across three years, two sites and three
      biological replicates per site. RESULTS: QTL specific to bark texture were highly
      reproducible in shared intervals across sites, years and replicates. Significant
      positive correlations and co-localization between trait QTL suggest pleiotropic
      regulators or closely linked genes. A list of candidate genes with related
      putative function, location close to QTL maxima and with the highest expression
      level in the phloem, xylem and cambium was identified. CONCLUSION: Candidate
      genes for bark texture included an ortholog of Arabidopsis ANAC104 (PopNAC128),
      which plays a role in lignified fiber cell and ray development, as well as Pinin
      and Fasciclin (PopFLA) genes with a role in cell adhesion, cell shape and
      migration. The results presented in this study provide a basis for future genomic
      characterization of genes found within the QTL for bark texture, bark thickness
      and diameter in order to better understand stem and bark development in Populus
      and other woody perennial plants. The QTL mapping approach identified a list of
      prime candidate genes for further validation using functional genomics or forward
      genetics approaches.

PMID- 29179674
TI  - Value of soluble Urokinase plasminogen activator receptor over age as a biomarker
      of impaired myocardial relaxation.
AB  - BACKGROUND: SuPAR is a biomarker that reflects the level of immune activation. As
      inflammation plays an important role in the ageing process of the cardiovascular
      system, we hypothesized that suPAR might be a useful predictive biomarker of the
      ageing heart. METHODS: We performed conventional and tissue Doppler
      echocardiography and measured plasma suPAR levels. RESULTS: We studied community
      adults (n=120, 37.5% female) (mean age: 70.3+/-9.3 years) without known
      cardiovascular disease (CVD). Participants with impaired myocardial relaxation
      were older (84% vs 59% were aged >=71 years, p=0.002), with more diabetes
      mellitus (27% vs 11%, p=0.034). SuPAR levels were higher among participants with
      impaired myocardial relaxation (3.9 ng/ml vs 3.0 ng/ml, p=0.015). At the
      univariate level, older age (OR 3.6; 95%CI 1.6, 8.5; p=0.003), diabetes mellitus
      (OR 3.04; 95%CI 1.1, 8.8; p=0.04), systolic blood pressure (OR 1.03; 95%CI 1.001,
      1.1; p=0.041) and suPAR levels >=3.00ng/ml (OR 3.4; 95%CI 1.16, 7.4; p=0.002)
      were associated with impaired myocardial relaxation. In multivariable regression
      analysis, only older age (OR 2.8; 95%CI 1.1, 6.7; p=0.026) and suPAR (OR 2.7;
      95%CI 1.2, 6.1; p=0.018) remained independently associated with impaired
      myocardial relaxation. Receiver operating characteristics (ROC) curve analysis
      revealed an area under the curve (AUC) value of 0.63 (95% CI 0.54, 0.71) for
      model that included age alone. Addition of suPAR significantly increased AUC
      value to 0.70 (95%CI 0.60, 0.79), which was significantly larger than the model
      with age alone (p=0.016). CONCLUSION: We demonstrate additional ability of suPAR,
      over age, to predict impaired myocardial relaxation. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02791139 (Registered May 31, 2016).

PMID- 29179676
TI  - HLA genotyping by next-generation sequencing of complementary DNA.
AB  - BACKGROUND: Genotyping of the human leucocyte antigen (HLA) is indispensable for
      various medical treatments. However, unambiguous genotyping is technically
      challenging due to high polymorphism of the corresponding genomic region. Next
      generation sequencing is changing the landscape of genotyping. In addition to
      high throughput of data, its additional advantage is that DNA templates are
      derived from single molecules, which is a strong merit for the phasing problem.
      Although most currently developed technologies use genomic DNA, use of cDNA could
      enable genotyping with reduced costs in data production and analysis. We thus
      developed an HLA genotyping system based on next-generation sequencing of cDNA.
      METHODS: Each HLA gene was divided into 3 or 4 target regions subjected to PCR
      amplification and subsequent sequencing with Ion Torrent PGM. The sequence data
      were then subjected to an automated analysis. The principle of the analysis was
      to construct candidate sequences generated from all possible combinations of
      variable bases and arrange them in decreasing order of the number of reads. Upon
      collecting candidate sequences from all target regions, 2 haplotypes were usually
      assigned. Cases not assigned 2 haplotypes were forwarded to 4 additional
      processes: selection of candidate sequences applying more stringent criteria,
      removal of artificial haplotypes, selection of candidate sequences with a relaxed
      threshold for sequence matching, and countermeasure for incomplete sequences in
      the HLA database. RESULTS: The genotyping system was evaluated using 30 samples;
      the overall accuracy was 97.0% at the field 3 level and 98.3% at the G group
      level. With one sample, genotyping of DPB1 was not completed due to short read
      size. We then developed a method for complete sequencing of individual molecules
      of the DPB1 gene, using the molecular barcode technology. CONCLUSION: The
      performance of the automatic genotyping system was comparable to that of systems
      developed in previous studies. Thus, next-generation sequencing of cDNA is a
      viable option for HLA genotyping.

PMID- 29179675
TI  - Cgl2 plays an essential role in cuticular wax biosynthesis in cabbage (Brassica
      oleracea L. var. capitata).
AB  - BACKGROUND: The aerial parts of most land plants are covered with cuticular wax
      which is important for plants to avoid harmful factors. There is still no cloning
      study about wax synthesis gene of the alcohol-forming pathway in Brassica
      species. RESULTS: Scanning electron microscopy (SEM) showed that, compared with
      wild type (WT), wax crystal are severely reduced in both the adaxial and abaxial
      sides of cabbage (Brassica oleracea L. var. capitata L.) leaves from the LD10GL
      mutant. Genetic analysis results revealed that the glossy trait of LD10GL is
      controlled by a single recessive gene, and fine mapping results revealed that the
      target gene Cgl2 (Cabbage glossy 2) is located within a physical region of 170 kb
      on chromosome 1. Based on sequence analysis of the genes in the mapped region,
      the gene designated Bol013612 was speculated to be the candidate gene. Gene
      Bol013612 is homologous to Arabidopsis CER4, which encodes fatty acyl-coenzyme A
      reductase. Sequencing identified a single nucleotide substitution at an
      intron/exon boundary that results in an insertion of six nucleotides in the cDNA
      of Bol013612 in LD10GL. The phenotypic defect of LD10GL was confirmed by a
      functional complementation test with Arabidopsis mutant cer4. CONCLUSIONS: Our
      results indicated that wax crystals of cabbage mutant LD10GL are severely reduced
      and mutation of gene Bol013612 causes a glossy phenotype in the LD10GL mutant.

PMID- 29179677
TI  - Robust transcriptional signatures for low-input RNA samples based on relative
      expression orderings.
AB  - BACKGROUND: It is often difficult to obtain sufficient quantity of RNA molecules
      for gene expression profiling under many practical situations. Amplification from
      low-input samples may induce artificial signals. RESULTS: We compared the
      expression measurements of low-input mRNA samples, from 25 pg to 1000 pg mRNA,
      which were amplified and profiled by Smart-seq, DP-seq and CEL-seq techniques
      using the Illumina HiSeq 2000 platform, with those of the paired high-input (50
      ng) mRNA samples. Even with 1000 pg mRNA input, we found that thousands of genes
      had at least 2 folds-change of expression levels in the low-input samples
      compared with the corresponding paired high-input samples. Consequently, a
      transcriptional signature based on quantitative expression values and determined
      from high-input RNA samples cannot be applied to low-input samples, and vice
      versa. In contrast, the within-sample relative expression orderings (REOs) of
      approximately 90% of all the gene pairs in the high-input samples were maintained
      in the paired low-input samples with 1000 pg input mRNA molecules. Similar
      results were observed in the low-input total RNA samples amplified and profiled
      by the Whole-Genome DASL technique using the Illumina HumanRef-8 v3.0 platform.
      As a proof of principle, we developed REOs-based signatures from high-input RNA
      samples for discriminating cancer tissues and showed that they can be robustly
      applied to low-input RNA samples. CONCLUSIONS: REOs-based signatures determined
      from the high-input RNA samples can be robustly applied to samples profiled with
      the low-input RNA samples, as low as the 1000 pg and 250 pg input samples but no
      longer stable in samples with less than 250 pg RNA input to a certain degree.

PMID- 29179678
TI  - A prediction model for the grade of liver fibrosis using magnetic resonance
      elastography.
AB  - BACKGROUND: Liver stiffness measurement (LSM) has recently become available for
      assessment of liver fibrosis. We aimed to develop a prediction model for liver
      fibrosis using clinical variables, including LSM. METHODS: We performed a
      prospective study to compare liver fibrosis grade with fibrosis score. LSM was
      measured using magnetic resonance elastography in 184 patients that underwent
      liver resection, and liver fibrosis grade was diagnosed histologically after
      surgery. Using the prediction model established in the training group, we
      validated the classification accuracy in the independent test group. RESULTS:
      First, we determined a cut-off value for stratifying fibrosis grade using LSM in
      122 patients in the training group, and correctly diagnosed fibrosis grades of 62
      patients in the test group with a total accuracy of 69.3%. Next, on least
      absolute shrinkage and selection operator analysis in the training group, LSM (r
      = 0.687, P < 0.001), indocyanine green clearance rate at 15 min (ICGR15) (r =
      0.527, P < 0.001), platelet count (r = -0.537, P < 0.001) were selected as
      variables for the liver fibrosis prediction model. This prediction model applied
      to the test group correctly diagnosed 32 of 36 (88.8%) Grade I (F0 and F1)
      patients, 13 of 18 (72.2%) Grade II (F2 and F3) patients, and 7 of 8 (87.5%)
      Grade III (F4) patients in the test group, with a total accuracy of 83.8%.
      CONCLUSIONS: The prediction model based on LSM, ICGR15, and platelet count can
      accurately and reproducibly predict liver fibrosis grade.

PMID- 29179679
TI  - Attenuating the rate of total body fat accumulation and alleviating liver damage
      by oral administration of vitamin D-enriched edible mushrooms in a diet-induced
      obesity murine model is mediated by an anti-inflammatory paradigm shift.
AB  - BACKGROUND: Hypovitaminosis D is associated with many features of the metabolic
      syndrome, including non-alcoholic fatty liver disease. Vitamin D-enriched
      mushrooms extracts exert a synergistic anti-inflammatory effect. The aim of the
      present study is to determine the immunomodulatory effect of oral administration
      of vitamin D-enriched mushrooms extracts on high-fat diet (HFD) animal model of
      non-alcoholic steatohepatitis (NASH). METHODS: C57BL/6 mice on HFD were orally
      administered with vitamin D supplement, Lentinula edodes (LE) mushrooms extract,
      or vitamin D-enriched mushrooms extract for 25 weeks. Mice were studied for the
      effect of the treatment on the immune system, liver functions and histology,
      insulin resistance and lipid profile. RESULTS: Treatment with vitamin D-enriched
      LE extracts was associated with significant attenuation of the rate of total body
      fat accumulation, along with a decrease in hepatic fat content as measured by an
      EchoMRI. Significant alleviation of liver damage manifested by a marked decrease
      in ALT, and AST serum levels (from 900 and 1021 U/L in the control group to 313
      and 340; 294 and 292; and 366 and 321 U/L for ALT and AST, in Vit D, LE and LE +
      Vit D treated groups, respectively). A corresponding effect on hepatocyte
      ballooning were also noted. A significant decrease in serum triglycerides (from
      103 to 75, 69 and 72 mg/dL), total cholesterol (from 267 to 160, 157 and 184
      mg/dL), and LDL cholesterol (from 193 mg/dL to 133, 115 and 124 mg/dL) along with
      an increase in the HDL/LDL ratio, and improved glucose levels were documented.
      These beneficial effects were associated with a systemic immunomodulatory effect
      associated with an increased CD4/CD8 lymphocyte ratio (from 1.38 in the control
      group to 1.69, 1.71 and 1.63), and a pro- to an anti-inflammatory cytokine shift.
      CONCLUSIONS: Oral administration of vitamin-D enriched mushrooms extracts exerts
      an immune modulatory hepato-protective effect in NASH model.

PMID- 29179680
TI  - Stercoral colitis complicated with ischemic colitis: a double-edge sword.
AB  - BACKGROUND: Stercoral colitis is a rare inflammatory process involving the
      colonic wall secondary to fecal impaction with high morbidity and mortality;
      especially if complicated with ischemic colitis, stercoral ulcer formation and
      subsequent perforation. There are several case reports published on abdominal
      perforation resulting from stercoral colitis. However, stercoral colitis
      complicated by ischemic colitis is rare. The purpose of this case report is to
      describe the potential challenges in the diagnosis and management of stercoral
      colitis with ischemic colitis. CASE PRESENTATION: An 87 years old male with
      history of chronic constipation presents with severe abdominal pain to the
      emergency department. The patient was hemodynamically stable. On physical
      examination, the abdomen was mildly distended with moderate tenderness. Lab work
      was significant for leukocytosis and lactic acidosis. Abdominal CT scan revealed
      large amount of retained stool in the colon, bowel wall thickening and
      infiltration of peri-colonic fat, which were suggestive for stercoral colitis.
      Patient was started on IV fluids and antibiotics. He was given an enema, followed
      by laxative and manual disimpaction of stool. Colonoscopy was performed and
      biopsies were obtained. Tissue biopsy was significant for focal active colitis
      with regenerative glandular changes and neural hyperplasia. CONCLUSION: Elevated
      lactic acid level secondary to ischemia of the bowel wall with CT scan findings
      aid in establishing the diagnosis of stercoral colitis complicated with ischemic
      colitis. Urgent treatment with laxatives and fecal disimpaction is indicated to
      prevent perforation and peritonitis.

PMID- 29179681
TI  - Low flow extracorporeal CO2 removal in ARDS patients: a prospective short-term
      crossover pilot study.
AB  - BACKGROUND: Lung protective mechanical ventilation (MV) is the corner stone of
      therapy for ARDS. However, its use may be limited by respiratory acidosis. This
      study explored feasibility of, effectiveness and safety of low flow
      extracorporeal CO2 removal (ECCO2R). METHODS: This was a prospective pilot study,
      using the Abylcap(r) (Bellco) ECCO2R, with crossover off-on-off design (2-h
      blocks) under stable MV settings, and follow up till end of ECCO2R. Primary
      endpoint for effectiveness was a 20% reduction of PaCO2 after the first 2-h.
      Adverse events (AE) were recorded prospectively. We included 10 ARDS patients on
      MV, with PaO2/FiO2 < 150 mmHg, tidal volume <= 8 mL/kg with positive end
      expiratory pressure >= 5 cmH2O, FiO2 titrated to SaO2 88-95%, plateau pressure >=
      28 cmH2O, and respiratory acidosis (pH <7.25). RESULTS: After 2-h of ECCO2R, 6
      patients had a >= 20% decrease in PaCO2 (60%); PaCO2 decreased 28.4% (from 58.4
      to 48.7 mmHg, p = 0.005), and pH increased (1.59%, p = 0.005). ECCO2R was
      hemodynamically well tolerated. During the whole period of ECCO2R, 6 patients had
      an AE (60%); bleeding occurred in 5 patients (50%) and circuit thrombosis in 3
      patients (30%), these were judged not to be life threatening. CONCLUSIONS: In
      ARDS patients, low flow ECCO2R significantly reduced PaCO2 after 2 h, Follow up
      during the entire ECCO2R period revealed a high incidence of bleeding and circuit
      thrombosis. TRIAL REGISTRATION: https://clinicaltrials.gov identifier:
      NCT01911533 , registered 23 July 2013.

PMID- 29179682
TI  - Faecal bacterial microbiota in patients with cirrhosis and the effect of
      lactulose administration.
AB  - BACKGROUND: Gut microbiota may be altered in patients with cirrhosis, and may
      further change after administration of lactulose. We studied the composition of
      gut microbiota in patients with cirrhosis and assessed the effect on it of
      lactulose administration. METHODS: Stool specimens were collected from 35
      patients with cirrhosis (male 26; median [range] age: 42 [29-65] years) and 18
      healthy controls (male 14; 44.5 [24-67] years); 21 patients provided another
      specimen after lactulose administration for 55 [42-77] days. For each, a DNA
      library of V3 region of bacterial 16S ribosomal RNA was subjected to paired-end
      Illumina sequencing. Inter-specimen relationship was studied using principal co
      ordinate analysis. Abundances of various bacterial taxa, and indices of alpha and
      beta diversity were compared, between patients and controls, and between
      specimens collected before and after lactulose. RESULTS: Gut microbiota from
      cirrhosis patients and controls showed differential clustering, and microbiota
      from patients with cirrhosis had less marked alpha diversity. Abundances of
      dominant phyla (Bacteroidetes, Firmicutes and Proteobacteria) were similar.
      However, patients with cirrhosis had lower abundances of five phyla, namely
      Tenericutes, Cyanobacteria, Spirochaetes, Elusimicrobia and Lentisphaerae, and
      differences in abundances of several families and genera than in controls.
      Lactulose administration did not lead to any change in alpha and beta
      diversities, species richness and abundances of various bacterial taxa in gut
      microbiota. CONCLUSIONS: Gut microbiota in cirrhosis differ from healthy persons
      and do not change following lactulose administration. The latter suggests that
      the effect of lactulose on hepatic encephalopathy may not be related to
      alteration in gut microbiota.

PMID- 29179683
TI  - Exercise during pregnancy on maternal lipids: a secondary analysis of randomized
      controlled trial.

PMID- 29179684
TI  - Potential applications of a new short food frequency questionnaire for CKD
      patients.
AB  - Diet is among the most modifiable risk factors for chronic kidney disease (CKD)
      progression. Studies of beneficial dietary patterns for persons with CKD have
      largely utilized dietary assessment measures developed in individuals without
      CKD. In BMC Nephrology, Affret et al. report on their study of the
      reproducibility of a newly developed short 49-item food frequency questionnaire
      (SFFQ) adapted to patients with CKD. Here, we discuss potential applications of
      this SFFQ, towards better understanding of which dietary patterns portend the
      most favorable outcomes in CKD.

PMID- 29179685
TI  - Frequency of data extraction errors and methods to increase data extraction
      quality: a methodological review.
AB  - BACKGROUND: Our objective was to assess the frequency of data extraction errors
      and its potential impact on results in systematic reviews. Furthermore, we
      evaluated the effect of different extraction methods, reviewer characteristics
      and reviewer training on error rates and results. METHODS: We performed a
      systematic review of methodological literature in PubMed, Cochrane methodological
      registry, and by manual searches (12/2016). Studies were selected by two
      reviewers independently. Data were extracted in standardized tables by one
      reviewer and verified by a second. RESULTS: The analysis included six studies;
      four studies on extraction error frequency, one study comparing different
      reviewer extraction methods and two studies comparing different reviewer
      characteristics. We did not find a study on reviewer training. There was a high
      rate of extraction errors (up to 50%). Errors often had an influence on effect
      estimates. Different data extraction methods and reviewer characteristics had
      moderate effect on extraction error rates and effect estimates. CONCLUSION: The
      evidence base for established standards of data extraction seems weak despite the
      high prevalence of extraction errors. More comparative studies are needed to get
      deeper insights into the influence of different extraction methods.

PMID- 29179686
TI  - Piloting electronic screening forms in primary care: findings from a mixed
      methods study to identify patients eligible for low dose CT lung cancer
      screening.
AB  - BACKGROUND: Recent evidence suggests that screening with low dose computed
      tomography (LDCT) scans significantly reduces mortality from lung cancer.
      However, optimal methods to identify potentially eligible patients in primary
      care are not known. Using brief electronic screening forms administered prior to
      a primary care visit is a strategy to identify high risk, asymptomatic patients
      eligible for LDCT screening. The objective of this study was to compare the
      acceptability and feasibility of using brief electronic versus paper screening
      forms to identify eligible patients at high risk of developing lung cancer in
      primary care. METHODS: A mixed method pilot comparative study was conducted in
      primary care. Practices were allocated to an electronic form (e-form) group or a
      paper-based form (p-form) group. Allocation was randomly assigned for the first
      practice then by alternation. Patients in the e-form practices completed forms at
      home via the web or in the waiting room on a tablet. Patients in p-form practices
      completed forms in waiting rooms. Interviews were conducted with patients,
      administrators, and primary care physicians (PCPs) about their experiences.
      RESULTS: Six of 30 (20%) eligible practices agreed to participate. Over the 16
      week study period, a total of 831 of an expected 1442 patients (58%) aged 55-74
      years were enrolled; 573/690 (83%) patients in the e-form group and 258/752 (34%)
      in the p-form group. Of the 573 participants in the e-form group, 335 (58%)
      completed forms via the web; 238 (29%) did so via tablet. Twenty-four interviews
      were conducted with 15 patients, 5 administrative staff and 4 PCPs. Patients were
      willing to discuss lung cancer screening eligibility with their PCP. Staff
      members expressed low administrative burden except for an extra step to link
      appointment information to patient demographics to identify eligible patients.
      PCPs indicated that forms were reminders to discuss smoking cessation. PCPs in
      the e-form group reported that patients asked questions about screening.
      CONCLUSION: There was fairly low uptake by primary care practices. For e-forms to
      be feasible in practice workflow, electronic medical record software needs to
      link appointment information with patient eligibility requirements. The use of
      brief pre-consultation electronic screening forms for LDCT eligibility encouraged
      PCPs to discuss smoking cessation with patients.

PMID- 29179687
TI  - Faecal microbiota transplantation: a regulatory hurdle?
AB  - During faecal microbiota transplantation, stool from a healthy donor is
      transplanted to treat a variety of dysbiosis-associated gut diseases. Competent
      authorities are faced with the challenge to provide adequate regulation.
      Currently, regulatory harmonization is completely lacking and authorities apply
      non-existing to most stringent requirements. A regulatory approach for faecal
      microbiota transplantation could be inserting faecal microbiota transplantation
      in the gene-, cell- and tissue regulations, including the hospital exemption
      system in the European Advanced Therapy Medicinal Products regulation, providing
      a pragmatic and efficacy-risk balanced approach and granting all patients as a
      matter of principle access to this therapy.

PMID- 29179688
TI  - Evaluating genetic ancestry and self-reported ethnicity in the context of carrier
      screening.
AB  - BACKGROUND: Current professional society guidelines recommend genetic carrier
      screening be offered on the basis of ethnicity, or when using expanded carrier
      screening panels, they recommend to compute residual risk based on ethnicity. We
      investigated the reliability of self-reported ethnicity in 9138 subjects referred
      to carrier screening. Self-reported ethnicity gathered from test requisition
      forms and during post-test genetic counseling, and genetic ancestry predicted by
      a statistical model, were compared for concordance. RESULTS: We identified
      several discrepancies between the two sources of self-reported ethnicity and
      genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry
      during consultation self-reported this on requisition forms. Additionally, the
      proportion of individuals who reported Southeast Asian but were estimated to have
      a different genetic ancestry was found to depend on the source of self-report.
      Finally, individuals who reported Latin American demonstrated a high degree of
      ancestral admixture. As a result, carrier rates and residual risks provided for
      patient decision-making are impacted if using self-reported ethnicity.
      CONCLUSION: Our analysis highlights the unreliability of ethnicity classification
      based on patient self-reports. We recommend the routine use of pan-ethnic carrier
      screening panels in reproductive medicine. Furthermore, the use of an ancestry
      model would allow better estimation of carrier rates and residual risks.

PMID- 29179689
TI  - The optimum sevoflurane concentration for supraglottic airway device
      BlockbusterTM insertion with spontaneous breathing in obese patients: a
      prospective observational study.
AB  - BACKGROUND: Airway management of the obese patient presenting for surgery is more
      likely to be a challenging problem. Supraglottic airway device has been adopted
      as a bridge to connect ventilation and tracheal intubation in obese patients who
      would be suffered with difficult intubation. The optimum sevoflurane
      concentration for supraglottic airway device insertion allowing spontaneous
      breathing in 50% of obese patients (ED50) is not known. The purpose of this study
      was to determine the ED50 of sevoflurane for supraglottic airway device
      BlockbusterTM insertion with spontaneous breathing in obese patients requiring
      general anesthesia. METHODS: Thirty elective obese patients (body mass index 30
      50 kg/m2) undergoing bariatric surgery were recruited in this study. The
      predetermined target sevoflurane concentration (initiating at 2.5% with 0.5% as a
      step size) was sustained for >5 min using a modified Dixon's up-and-down method,
      and then the supraglottic airway device BlockbusterTM was inserted. The patient's
      response to supraglottic airway device insertion was classified as either
      'movement' or 'no-movement'. The ED50 of sevoflurane were determined by
      calculating the midpoint concentration of crossover point from 'movement' or 'no
      movement' response. RESULTS: The ED50 of sevoflurane for supraglottic airway
      device BlockbusterTM insertion in obese patients calculated using up-and-down
      method were 2.50 +/- 0.60%. The ED50 and ED95 (95% confidence interval) obtained
      by probit regression analysis were 2.35 (1.28-3.42) % and 4.03 (3.16-17.83) % for
      supraglottic airway device BlockbusterTM insertion, respectively. CONCLUSION: We
      conclude that the optimum end-tidal sevoflurane concentration required for the
      supraglottic airway device BlockbusterTM insertion allowing spontaneous breathing
      in 50% of obese patients (ED50) is 2.5 +/- 0.6%. TRIAL REGISTRATION: Chinese
      Clinical Trial Registry, ChiCTR-IPR-16009071 , Registered on 24 August 2016.

PMID- 29179690
TI  - Unique proximal tubular cell injury and the development of acute kidney injury in
      adult patients with minimal change nephrotic syndrome.
AB  - BACKGROUND: Adult patients with minimal change nephrotic syndrome (MCNS) are
      often associated with acute kidney injury (AKI). To assess the mechanisms of AKI,
      we examined whether tubular cell injuries unique to MCNS patients exist. METHODS:
      We performed a retrospective analysis of clinical data and tubular cell changes
      using the immunohistochemical expression of vimentin as a marker of tubular
      injury and dedifferentiation at kidney biopsy in 37 adult MCNS patients. AKI was
      defined by the criteria of the Kidney Disease: Improving Global Outcomes (KDIGO)
      Clinical Practice Guidelines for AKI. RESULTS: Thirteen patients (35.1%) were
      designated with AKI at kidney biopsy. No significant differences in age, history
      of hypertension, chronic kidney disease, diuretics use, proteinuria, and serum
      albumin were noted between the AKI and non-AKI groups. Urinary N-acetyl-beta-D
      glucosaminidase (uNAG) and urinary alpha1-microglobulin (uA1MG) as markers of
      tubular injury were increased in both groups, but the levels were significantly
      increased in the AKI group compared with the non-AKI group. The incidence of
      vimentin-positive tubules was comparable between AKI (84.6%) and non-AKI (58.3%)
      groups, but vimentin-positive tubular area per interstitial area was
      significantly increased in the AKI group (19.8%) compared with the non-AKI group
      (6.8%) (p = 0.011). Vimentin-positive injured tubules with tubular simplification
      (loss of brush-border of the proximal tubule/dilated tubule with flattening of
      tubular epithelium) were observed in the vicinity of glomeruli in both groups,
      suggesting that the proximal convoluted tubules were specifically injured. Two
      patients exhibited relatively severe tubular injuries with vimentin positivity
      and required dialysis within 2 weeks after kidney biopsy. The percentage of the
      vimentin-positive tubular area was positively correlated with uNAG but not with
      uA1MG in the non-AKI group. CONCLUSIONS: Proximal tubular injuries with increased
      uNAG exist in MCNS patients without renal dysfunction and were more severe in the
      AKI group than they were in the non-AKI group. The unique tubular injuries
      probably due to massive proteinuria might be a predisposing factor for the
      development of severe AKI in adult MCNS patients.

PMID- 29179691
TI  - Comparison of sedation between the endoscopy room and operation room during
      endoscopic submucosal dissection for neoplasms in the upper gastrointestinal
      tract.
AB  - BACKGROUND: The present study was performed to compare the safety of sedation
      during endoscopic submucosal dissection (ESD) in the endoscopy room versus
      operation room. METHODS: In total, 297 patients with gastrointestinal tumors who
      underwent ESD from January 2011 to December 2016 were retrospectively reviewed.
      The patients were divided into two groups: those who underwent ESD in the
      endoscopy room without propofol (Group E) versus operation room with propofol
      (Group O). The patient, tumor, and procedure characteristics; adverse events; and
      treatment outcomes were compared between the two groups. RESULTS: The patient and
      tumor characteristics, including age (73.6 +/- 8.2 vs. 72.5 +/- 9.1 years),
      comorbidities, and tumor size and histology, were not different between Groups E
      and O. The ESD procedure time was comparable between Groups E and O (105.4 +/-
      70.4 vs. 106.5 +/- 64.4 min), and the anesthesia time was equivalent (138.3 +/-
      78.1 vs. 148.4 +/- 68.8 min). There were no significant differences in adverse
      events between the two groups. During the ESD procedure, desaturation occurred
      significantly more often in Group E than O (12.9% vs. 4.0%, P = 0.021, odds
      ratio: 3.53, 95% CI: 1.17-14.4). The recovery time after ESD was significantly
      longer in Group E than O (180 (100-360) vs. 90 (0-180) min, P < 0.001).
      CONCLUSIONS: A decreased desaturation rate and shorter recovery time after ESD
      were the advantages of sedation in the operation room with propofol compared with
      sedation in the endoscopy room. These findings warrant further exploration of the
      advantages of safe and effective ESD for upper gastrointestinal neoplasms in the
      operation room.

PMID- 29179692
TI  - Dietary habits and obesity indices in patients with gastro-esophageal reflux
      disease: a comparative cross-sectional study.
AB  - BACKGROUND: Gastro-esophageal reflux disease (GERD) is suggested to be associated
      with some socio-demographic and lifestyle factors. Although the roles of some
      factors such as obesity are well documented, evidence on the impact of other
      factors such as dietary habits are still inconclusive. The aim of this study was
      to determine the relationship between socio-demographic and lifestyle factors
      with GERD in participants referred to a teaching hospital in Zahedan, South-East
      of Iran. METHODS: This comparative cross-sectional study was conducted during
      2014-2015. All patients completed a structured questionnaire regarding
      information on socio-demographic status, lifestyle factors and dietary habits.
      Anthropometric indices including body mass index (BMI) and waist circumference
      (WC) were used to determine general and central obesity, respectively. Data were
      analyzed using SPSS software version 22. Value of p < 0.05 was considered as
      statistically significant. RESULTS: Five hundred and five participants, including
      285 GERD and 220 Non-GERD participants participated in the study. In univariate
      analysis, being married (OR = 1.57, 95%CI = 1.04, 2.36), general obesity (OR =
      1.77, 95%CI = 1.11, 2.81), central obesity (OR = 2.09, 95%CI = 1.46,3.01) and
      consumption of citrus fruits between meals (OR = 1.69, 95%CI = 1.04, 2.73) were
      associated with higher odds of GERD, while higher educational level (OR = 0.53,
      95%CI = 0.36,0.77) and regular physical activity >=2 h/week (OR = 0.53, 95%CI =
      0.30, 0.94) were associated with lower odds of GERD. In the adjusted model,
      central obesity (OR = 1.88, 95%CI = 1.18, 3.01) and consumption of citrus fruits
      between meals (OR = 2.22, 95%CI = 1.30, 3.81) were positively associated with
      odds of GERD, while higher educational level (OR = 0.55, 95%CI = 0.33, 0.91) was
      associated with decreased odds of GERD. CONCLUSION: According to the results of
      the current study, central obesity as determined by WC and citrus fruit intake
      were independent factors associated with GERD. Therefore, lifestyle modification
      might have a positive effect in the treatment of GERD in an urban population of
      Iran.

PMID- 29179694
TI  - Correction to: Protocol for the Emory University African American Vaginal, oral,
      and gut microbiome in pregnancy cohort study.
AB  - Following publication of the original article [1], the authors pointed out that
      the Methods included one step that is no longer necessary but which was
      inadvertently carried over from an earlier protocol.

PMID- 29179693
TI  - Unloading shoes for intermittent claudication: a randomised crossover trial.
AB  - BACKGROUND: The purpose of this study was to assess the functional effects and
      acceptability of rocker-soled shoes that were designed to relatively "unload" the
      calf muscles during walking in people with calf claudication due to peripheral
      arterial disease. METHODS: In this randomised AB/BA crossover trial, participants
      completed two assessment visits up to two weeks apart. At each visit,
      participants completed walking tests whilst wearing the unloading shoes or
      visually-similar control shoes. At the end of the second visit, participants were
      given either the unloading or control shoes to use in their home environment for
      2 weeks, with the instruction to wear them for at least 4 h every day. The
      primary outcome was 6-min walk distance. We also assessed pain-free walking
      distance and gait biomechanical variables during usual-pace walking, adverse
      events, and participants' opinions about the shoes. Data for continuous outcomes
      are presented as mean difference between conditions with corresponding 95%
      confidence interval. RESULTS: Thirty-four participants (27 males, mean age 68
      years, mean ankle-brachial index 0.54) completed both assessment visits. On
      average, the 6-min walk distance was 11 m greater when participants wore the
      control shoes (95% CI -5 to 26), whereas mean pain-free walking distance was 7 m
      greater in the unloading shoes (95% CI -17 to 32). Neither of these differences
      were statistically significant (p = 0.18 and p = 0.55, respectively). This was
      despite the unloading shoes reducing peak ankle plantarflexion moment (mean
      difference 0.2 Nm/kg, 95% CI 0.0 to 0.3) and peak ankle power generation (mean
      difference 0.6 W/kg, 95% CI 0.2 to 1.0) during pain-free walking. The survey and
      interview data was mixed, with no clear differences between the unloading and
      control shoes. CONCLUSIONS: Shoes with modified soles to relatively unload the
      calf muscles during walking conferred no substantial acute functional benefit
      over control shoes. TRIAL REGISTRATION: Clinicaltrials.gov, Trial Registration
      Number: NCT02505503 , First registered 22 July 2015.

PMID- 29179695
TI  - Nonlocal total variation based on symmetric Kullback-Leibler divergence for the
      ultrasound image despeckling.
AB  - BACKGROUND: Ultrasound imaging is safer than other imaging modalities, because it
      is noninvasive and nonradiative. Speckle noise degrades the quality of ultrasound
      images and has negative effects on visual perception and diagnostic operations.
      METHODS: In this paper, a nonlocal total variation (NLTV) method for ultrasonic
      speckle reduction is proposed. A spatiogram similarity measurement is introduced
      for the similarity calculation between image patches. It is based on symmetric
      Kullback-Leibler (KL) divergence and signal-dependent speckle model for log
      compressed ultrasound images. Each patch is regarded as a spatiogram, and the
      spatial distribution of each bin of the spatiogram is regarded as a weighted
      Gamma distribution. The similarity between the corresponding bins of the two
      spatiograms is computed by the symmetric KL divergence. The Split-Bregman fast
      algorithm is then used to solve the adapted NLTV object function. Kolmogorov
      Smirnov (KS) test is performed on synthetic noisy images and real ultrasound
      images. RESULTS: We validate our method on synthetic noisy images and clinical
      ultrasound images. Three measures are adopted for the quantitative evaluation of
      the despeckling performance: the signal-to-noise ratio (SNR), structural
      similarity index (SSIM), and natural image quality evaluator (NIQE). For
      synthetic noisy images, when the noise level increases, the proposed algorithm
      achieves slightly higher SNRS than that of the other two algorithms, and the
      SSIMS yielded by the proposed algorithm is obviously higher than that of the
      other two algorithms. For liver, IVUS and 3DUS images, the NIQE values are 8.25,
      6.42 and 9.01, all of which are higher than that of the other two algorithms.
      CONCLUSIONS: The results of the experiments over synthetic and real ultrasound
      images demonstrate that the proposed method outperforms current state-of-the-art
      despeckling methods with respect to speckle reduction and tissue texture
      preservation.

PMID- 29179696
TI  - Secondary sclerosing cholangitis in localized hepatobiliary tuberculosis
      simulating cholangiocarcinoma: a rare case report.
AB  - BACKGROUND: Hepatobiliary tuberculosis includes miliary, tuberculous hepatitis or
      localized forms. The localised form is extremely uncommon and can mimic
      malignancy. Still rarer is its presentation as sclerosing cholangitis. CASE
      PRESENTATION: A 50 year male presented with acute onset jaundice, significant
      weight loss and elevated liver enzymes with clinico-radiological suspicion of
      cholangiocarcinoma. A left hepatectomy was done and dilated bile ducts filled
      with caseous necrotic material were seen intra-operatively. Histopathology
      suggested localized hepatobiliary tuberculosis with features of secondary
      sclerosing cholangitis. CONCLUSION: Localised hepatobiliary tuberculosis can
      cause diagnostic difficulties and its possibility should be considered especially
      in endemic areas.

PMID- 29179697
TI  - Identification and analysis of glutathione S-transferase gene family in sweet
      potato reveal divergent GST-mediated networks in aboveground and underground
      tissues in response to abiotic stresses.
AB  - BACKGROUND: Sweet potato, a hexaploid species lacking a reference genome, is one
      of the most important crops in many developing countries, where abiotic stresses
      are a primary cause of reduction of crop yield. Glutathione S-transferases (GSTs)
      are multifunctional enzymes that play important roles in oxidative stress
      tolerance and cellular detoxification. RESULTS: A total of 42 putative full
      length GST genes were identified from two local transcriptome databases and
      validated by molecular cloning and Sanger sequencing. Sequence and intraspecific
      phylogenetic analyses revealed extensive differentiation in their coding
      sequences and divided them into eight subfamilies. Interspecific phylogenetic and
      comparative analyses indicated that most examined GST paralogs might originate
      and diverge before the speciation of sweet potato. Results from large-scale RNA
      seq and quantitative real-time PCR experiments exhibited extensive variation in
      gene-expression profiles across different tissues and varieties, which implied
      strong evolutionary divergence in their gene-expression regulation. Moreover, we
      performed five manipulated stress experiments and uncovered highly divergent
      stress-response patterns of sweet potato GST genes in aboveground and underground
      tissues. CONCLUSIONS: Our study identified a large number of sweet potato GST
      genes, systematically investigated their evolutionary diversification, and
      provides new insights into the GST-mediated stress-response mechanisms in this
      worldwide crop.

PMID- 29179699
TI  - Gastrointestinal tuberculosis following renal transplantation accompanied with
      septic shock and acute respiratory distress syndrome: a survival case
      presentation.
AB  - BACKGROUND: Post-transplant tuberculosis (PTTB) is a serious opportunistic
      infection in renal graft recipients with a 30-70 fold higher incidence compared
      to the general population. PTTB occurs most frequently within the first years
      after transplantation, manifesting as pulmonary or disseminated TB.
      Gastrointestinal TB (GITB) is a rare and potentially lethal manifestation of PTTB
      and may show delayed onset in renal transplant recipients due to the use of lower
      doses of immunosuppressants. Further, non-specificity of symptoms and the common
      occurrence of GI disorders in transplant recipients may delay diagnosis of GITB.
      CASE PRESENTATION: Here we report a rare survival case of isolated GITB in a
      renal transplant recipient, occurring seven years after transplantation. The
      patient's condition was complicated by severe sepsis with positive blood culture
      Staphylococcus haemolyticus, septic shock, multiple organ failure including acute
      respiratory distress syndrome (ARDS) and acute renal failure, requiring
      mechanical ventilation, vasopressor circulatory support and intermittent
      hemodialysis. Furthermore, nosocomial infections such as invasive aspergillosis
      and Pseudomonas aeruginosa occurred during hospitalization. Antituberculosis
      therapy (rifampicin, isoniazid, ethambutol and pyrazinamide) was initiated upon
      Mycobacterium confirmation. Moreover, treatment with voriconazole due to the
      Aspergillus flavus and meropenem due to the Pseudomonas aeruginosa was initiated,
      the former necessitating discontinuation of rifampicin. After 34 days, the
      patient was weaned from mechanical ventilation and was discharged to the
      pulmonary ward, followed by complete recovery. CONCLUSION: This case offers a
      guideline for the clinical management towards survival of GITB in transplant
      patients, complicated by septic shock and multiple organ failure, including acute
      renal injury and ARDS.

PMID- 29179698
TI  - Fast food diet-induced non-alcoholic fatty liver disease exerts early protective
      effect against acetaminophen intoxication in mice.
AB  - BACKGROUND: Acetaminophen (APAP) is a readily available and safe painkiller.
      However, its overdose is the most common cause of acute liver injury (ALI). Many
      predisposing factors contribute to susceptibility to APAP-induced ALI. Non
      alcoholic fatty liver disease (NAFLD), the major cause of chronic liver disease,
      is considered an important predictor of APAP-induced ALI, although the exact
      mechanism controversial. In this study, we aimed to elucidate the effects of
      NAFLD on APAP-induced ALI. METHODS: Two groups of mice, normal chow (NC) diet-fed
      and fast food (FF) diet-fed mice for 14 weeks, were further divided into two
      subgroups: intraperitoneally injected with either saline (NC-S and FF-S groups)
      or APAP (NC-A and FF-A groups). Biochemical tests, histological analysis,
      quantitative PCR, and western blotting were conducted. RESULTS: Alanine
      aminotransferase (ALT) level (199.0 +/- 39.0 vs. 63.8 +/- 7.4 IU/L, p < 0.05) and
      NAFLD activity score (0 vs. 4.5 +/- 0.22) were significantly higher in mice in FF
      S group than those in NC-S group. ALI features such as ALT level (8447.8 +/-
      1185.3 vs. 836.6 +/- 185.1 IU/L, p < 0.001) and centrizonal necrosis were
      prominent and mRNA levels of Trib3 (RR, 1.81) was high in mice in the NC-A group.
      Levels of CYP2E1 and anti-inflammatory molecules such as PPAR-gamma, p62, and
      NRF2 were high in mice in the FF-A group. CONCLUSIONS: Our results showed that
      while the FF diet clearly induced non-alcoholic steatohepatitis and metabolic
      syndrome, NAFLD also attenuates APAP-induced ALI by inducing anti-inflammatory
      molecules such as PPAR-gamma.

PMID- 29179701
TI  - The enablers, barriers and preferences of accessing radiation therapy facilities
      in the rural developed world - a systematic review.
AB  - BACKGROUND: Utilisation of radiation therapy for regional Australia and around
      the world has been the focus of much health policy the last decade. Radiation
      therapy centres have been built in Australian regional and rural areas to improve
      access to radiation therapy and reduce the tyranny of distance as a barrier to
      access. After this the enablers, barriers and perceptions of patients has been
      evaluated to determine utilisation once centres have been built. Thisreview looks
      the impact of rural radiation services in the developed world, barriers and
      enablers of establishing a rural radiation centre, and patients' and service
      providers' perspectives and preferences around the uptake of rural radiation
      therapy. METHODS: Online search of peer reviewed literature was undertaken using
      MeSH terms relating to the topic. Inclusion criteria were regional radiation
      therapy centres in developing countries, any year of publication, in English, and
      qualitative or quantitative methodologies. Articles were reviewed by two authors
      with conflicts discussed with a third. RESULTS: Twenty three studies addressed
      the theme directly. Distance barriers have been overcome by building regional
      centres and health economic burden was lower for government service providers
      with this strategy. However distance still plays an important role in influencing
      uptake of radiation therapy. Cultural expectations, influence of the family
      doctor and perception of care was influential. Carer support, duration of
      displacement from home, financial impact of the required care and seasonal
      weather were practical factors on a patient's decision. CONCLUSIONS: Regional
      radiation therapy centres have improved access to radiation therapy in developing
      countries. However the complex nuances between socio-economic, cultural and
      health system factors that influence regional patient's decision making bears
      further consideration, as distance is not the only issue.

PMID- 29179702
TI  - Foveal microvasculature features of surgically closed macular hole using optical
      coherence tomography angiography.
AB  - BACKGROUND: To describe the features of foveal microvasculature using optical
      coherence tomography angiography (OCTA) and to determine the related clinical
      factors in eyes with surgically closed macular hole (MH). METHODS: A
      retrospective case series of 18 patients with unilateral MH was reviewed. The
      patients maintained complete hole closure after vitrectomy with inner limiting
      membrane (ILM) peeling for at least 12 months. The healthy fellow eyes were
      studied as controls. The foveal microvasculature of both eyes was examined by
      OCTA. The area of the foveal avascular zone (FAZ) and the vascular density (VD)
      ratio in the superficial and deep capillary plexuses (SCP and DCP) were
      determined after surgery. Several clinical factors including age, stage and
      dimensions of MH, papillofoveal distance, the extent of nasal displacement of the
      fovea after surgery, postoperative central foveal thickness, and outer-retina
      integrity were evaluated to determine any relationships with the OCTA parameters.
      RESULTS: The mean FAZ area in both the SCP and DCP (0.29 +/- 0.11 mm2 and 0.39 +/
      0.14 mm2) was significantly smaller than those of the controls (0.45 +/- 0.14
      mm2 and 0.62 +/- 0.22 mm2) (p = 0.001 and <0.001, respectively). The mean VD
      ratio in the SCP (0.270 +/- 0.349) was similar to that of the controls (0.321 +/-
      0.189) (p = 0.231); however, that in the DCP (0.321 +/- 0.189) was significantly
      lower than that of the controls (0.331 +/- 0.119) (p = 0.025). Only the extent of
      nasal displacement of the fovea was correlated with the DCP FAZ-area difference
      values between the study group and the controls (correlation coefficient = 0.577;
      p = 0.012). CONCLUSIONS: After successful MH surgery, the FAZ area in both the
      SCP and DCP was smaller and the VD ratio of the DCP was lower, suggesting a
      possible DCP vulnerability to tractional stress. As the FAZ area of the DCP in
      closed-MH eyes became smaller than that in the controls, the fovea was less
      displaced toward the optic disc, possibly reflecting a lack of retinal redundancy
      caused by horizontal stretching accompanied by foveal displacement.

PMID- 29179700
TI  - Awareness, discussion and non-prescribed use of HIV pre-exposure prophylaxis
      among persons living with HIV/AIDS in Italy: a Nationwide, cross-sectional study
      among patients on antiretrovirals and their treating HIV physicians.
AB  - BACKGROUND: Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and
      made available, a few surveys among gay and bisexual men, and persons living with
      HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP
      among HIV-negative individuals. Before PrEP availability in Italy, we aimed to
      assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals,
      whether they knew people who were on PrEP, and describe the level of awareness
      and discussion on this preventive measure among them and people in their close
      circle. METHODS: Two anonymous questionnaires investigating personal
      characteristics and PrEP awareness, knowledge, and experience were proposed to
      HIV specialists and their patients on ARVs in a one-week, cross-sectional survey
      (December 2013-January 2014). Among PLWHA, a Multivariable Logistic Regression
      analysis was conducted to identify factors associated with PrEP discussion with
      peers (close circle and/or HIV associations), and experience (use in close circle
      and/or personal ARV sharing). RESULTS: Eighty-seven specialists in 31
      representative Infectious Diseases departments administered the questionnaire to
      1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage
      schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6%
      were somehow aware, discussed or had direct or indirect experience of PrEP: 38%
      "had heard" of PrEP, 24% were aware of studies in HIV-negative individuals
      demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP,
      12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing.
      Factors predictive of either PrEP discussion with peers or experience differed
      between men and women, but across all genders were mainly related to having
      access to information, with HIV association membership being the strongest
      predictor. CONCLUSIONS: At a time and place where there were neither official
      information nor proposals or interventions to guide public policies on PrEP in
      Italy, a significant number of PLWHA were aware of it, and approximately 10%
      reported PrEP use in their close circle, although they rarely shared their ARVs
      with uninfected people for this purpose. Official policies and PrEP availability,
      along with implementation programs, could avoid risks from uncontrolled PrEP
      procurement and self-administration practices.

PMID- 29179703
TI  - Is the content of guidelines/pathways a barrier for the integration of palliative
      Care in Chronic Heart Failure (CHF) and chronic pulmonary obstructive disease
      (COPD)? A comparison with the case of cancer in Europe.
AB  - BACKGROUND: There is a notable inequity in access to palliative care (PC)
      services between cancer and Chronic Heart Failure (CHF)/Chronic Obstructive
      Pulmonary Disease (COPD) patients which also translates into discrepancies in the
      level of integration of PC. By cross-examining the levels of PC integration in
      published guidelines/pathways for CHF/COPD and cancer in Europe, this study
      examines whether these discrepancies may be attributed to the content of the
      guidelines. DESIGN: A quantitative evaluation was made between integrated PC in
      published guidelines for cancer and CHF/COPD in Europe. The content of integrated
      PC in guidelines/pathways was measured using an 11 point integrated PC criteria
      tool (IPC criteria). A statistical analysis was carried out to detect
      similarities and differences in the level of integrated PC between the two
      groups. RESULTS: The levels of integration between CHF/COPD and cancer
      guidelines/pathways have been shown to be statistically similar. Moreover, the
      quality of evidence utilized and the date of development of the
      guidelines/pathways appear not to impact upon the PC integration in the
      guidelines. CONCLUSION: In Europe, the empirically observed imbalance in
      integration of PC for patients with cancer and CHF/COPD may only partially be
      attributed to the content of the guidelines/pathways that are utilized for the PC
      implementation. Given the similarities detected between cancer and CHF/COPD,
      other barriers appear to play a more prominent role.

PMID- 29179705
TI  - Vitrectomy with internal limiting membrane peeling versus inverted internal
      limiting membrane flap technique for macular hole-induced retinal detachment: a
      systematic review of literature and meta-analysis.
AB  - BACKGROUND: To evaluate the effects on vitrectomy with internal limiting membrane
      (ILM) peeling versus vitrectomy with inverted internal limiting membrane flap
      technique for macular hole-induced retinal detachment (MHRD). METHODS: Pubmed,
      Cochrane Library, and Embase were systematically searched for studies that
      compared ILM peeling with inverted ILM flap technique for macular hole-induced
      retinal detachment. The primary outcomes are the rate of retinal reattachment and
      the rate of macular hole closure 6 months later after initial surgery, the
      secondary outcome is the postoperative best-corrected visual acuity (BCVA) 6
      months later after initial surgery. RESULTS: Four studies that included 98 eyes
      were selected. All the included studies were retrospective comparative studies.
      The preoperative best-corrected visual acuity was equal between ILM peeling and
      inverted ILM flap technique groups. It was indicated that the rate of retinal
      reattachment (odds ratio (OR) = 0.14, 95% confidence interval (CI):0.03 to 0.69;
      P = 0.02) and macular hole closure (OR = 0.06, 95% CI:0.02 to 0.19; P < 0.00001)
      after initial surgery was higher in the group of vitrectomy with inverted ILM
      flap technique than that in the group of vitrectomy with ILM peeling. However,
      there was no statistically significant difference in postoperative best-corrected
      visual acuity (mean difference (MD) 0.18 logarithm of the minimum angle of
      resolution; 95% CI -0.06 to 0.43 ; P = 0.14) between the two surgery groups.
      CONCLUSION: Compared with ILM peeling, vitrectomy with inverted ILM flap
      technique resulted significantly higher of the rate of retinal reattachment and
      macular hole closure, but seemed does not improve postoperative best-corrected
      visual acuity.

PMID- 29179706
TI  - Intralobar pulmonary sequestration expanding toward the contralateral thorax: two
      case reports.
AB  - BACKGROUND: Intralobar pulmonary sequestration (ILS) is defined as a portion of
      parenchyma that is contained within the normal pleural investment of the lung but
      not connected to the tracheobronchial tree, and supplied by anomalous systemic
      arteries. As ILS is enveloped within the lobe of the normal lung, it is extremely
      rare for ILS to invade into the mediastinum. We report two atypical cases of
      infants with ILS expanded toward the posterior mediastinum and contralateral
      thorax through the pulmonary ligament. CASE PRESENTATION: The first case involved
      a baby boy diagnosed at 30 weeks gestation with a cystic area in his right lower
      lobe. A chest computed tomography (CT) scan at 29 days of life showed low-density
      masses in the right lower lung and posterior mediastinum. A complete
      thoracoscopic right lower lobectomy was performed at 19 months of age. After
      ligation of the aberrant systemic artery, the mediastinal mass was pulled into
      the right pleural cavity. The mass was observed to connect to the right lower
      lobe mass as a segment of lung parenchyma situated within the normal pleural
      investment of the lung, and the patient was diagnosed with ILS. The second case
      involved the detection by chest CT of a left lower lung cystic mass that
      protruded into the posterior mediastinum and contralateral chest of a one-month
      old baby girl. A complete thoracoscopic left lower lobectomy was performed at the
      age of 18 months, and the cystic mass located in the right thoracic cavity was
      pulled easily into the left pleural cavity and resected. An anomalous systemic
      artery was identified and ligated, and the patient was also diagnosed with ILS.
      CONCLUSIONS: As the pulmonary ligament consists of two layers of mediastinal
      pleura, lower lung ILS with its visceral pleura covering can, though rarely,
      protrude into the mediastinum through the pulmonary ligament. Our two extremely
      rare cases of infants with ILS expanded toward the posterior mediastinum and
      contralateral thorax were successfully treated using a unilateral thoracoscopic
      approach. Pre-surgical differential diagnosis of mediastinal masses using
      contrast-enhanced multiple detector CT is important in informing the appropriate
      surgical approach.

PMID- 29179704
TI  - Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to
      interact with P53 in leukemic cells.
AB  - BACKGROUND: As the important suppressor of P53, iASPP is found to be
      overexpressed in leukemia, and functions as oncogene that inhibited apoptosis of
      leukemia cells. Sertad1 is identified as one of the proteins that can bind with
      iASPP in our previous study by two-hybrid screen. METHODS: Co-immunoprecipitation
      and immunofluorescence were perfomed to identified the interaction between iASPP
      and Sertad1 protein. Westernblot and Real-time quantitative PCR were used to
      determine the expression and activation of proteins. Cell proliferation assays,
      cell cycle and cell apoptosis were examined by flow cytometric analysis. RESULTS:
      iASPP combined with Sertad1 in leukemic cell lines and the interaction occurred
      in the cytoplasm near nuclear membrane. iASPP could interact with Sertad1 through
      its Cyclin-A, PHD-bromo, C terminal domain, except for S domain. Overexpression
      of iASPP in leukemic cells resulted in the increased cell proliferation and
      resistance to apoptosis induced by chemotherapy drugs. While overexpression of
      iASPP and Sertad1 at the same time could slow down the cell proliferation, lead
      the cells more vulnerable to the chemotherapy drugs, the resistance to
      chemotherapeutic drug in iASPPhi leukemic cells was accompanied by Puma protein
      expression. Excess Sertad1 protein could tether iASPP protein in the cytoplasm,
      further reduced the binding between iASPP and P53 in the nucleus. CONCLUSIONS:
      Sertad1 could antagonize iASPP function by hindering its entrance into nuclei to
      interact with P53 in leukemic cells when iASPP was in the stage of
      overproduction.

PMID- 29179707
TI  - Selective impairment of decision making under ambiguity in alexithymia.
AB  - BACKGROUND: Alexithymia is characterised by difficulties identifying and
      describing emotions. Few studies have investigated how alexithymia influences
      decision-making under different conditions (ambiguity and risk). This study aimed
      to examine whether alexithymia contributes to impairment in decision-making.
      METHOD: This study included 42 participants with high scores in the Chinese
      version of Toronto Alexithymia Scale (alexithymia group), and 44 matched subjects
      with low scores (control group). Decision-making was measured using the Iowa
      Gambling Task (IGT) and the Game of Dice Task (GDT). RESULTS: The main findings
      of this study revealed selective deficits in IGT performance for the alexithymia
      group, while GDT performance was unimpaired when compared with the control group.
      In IGT, total netscores were lower for the alexithymia group compared to the
      control group, particularly with regard to block 5. Moreover, the alexithymia
      individuals selected significantly more adverse cards than the controls,
      indicating significant decision-making impairments. CONCLUSION: Alexithymia
      selectively influences decision-making under ambiguity.

PMID- 29179708
TI  - Comparing doctors' legal compliance across three Australian states for decisions
      whether to withhold or withdraw life-sustaining medical treatment: does different
      law lead to different decisions?
AB  - BACKGROUND: Law purports to regulate end-of-life care but its role in decision
      making by doctors is not clear. This paper, which is part of a three-year study
      into the role of law in medical practice at the end of life, investigates whether
      law affects doctors' decision-making. In particular, it considers whether the
      fact that the law differs across Australia's three largest states - New South
      Wales (NSW), Victoria and Queensland - leads to doctors making different
      decisions about withholding and withdrawing life-sustaining treatment from adults
      who lack capacity. METHODS: A cross-sectional postal survey of the seven
      specialties most likely to be involved in end-of-life care in the acute setting
      was conducted between 18 July 2012 and 31 January 2013. The sample comprised all
      medical specialists in emergency medicine, geriatric medicine, intensive care,
      medical oncology, palliative medicine, renal medicine and respiratory medicine on
      the AMPCo Direct database in those three Australian states. The survey measured
      medical specialists' level of legal compliance, and reasons for their decisions,
      concerning the withholding or withdrawal of life-sustaining treatment.
      Multivariable logistic regression was used to examine predictors of legal
      compliance. Linear regression was used to examine associations between the
      decision about life-sustaining treatment and the relevance of factors involved in
      making these decisions, as well as state differences in these associations.
      RESULTS: Response rate was 32% (867/2702). A majority of respondents in each
      state said that they would provide treatment in a hypothetical scenario, despite
      an advance directive refusing it: 72% in NSW and Queensland; 63% in Victoria.
      After applying differences in state law, 72% of Queensland doctors answered in
      accordance with local law, compared with 37% in Victoria and 28% in NSW (p <
      0.001). Doctors reported broadly the same decision-making approach despite
      differences in local law. CONCLUSIONS: Law appears to play a limited role in
      medical decision-making at the end of life with doctors prioritising patient
      related clinical and ethical considerations. Different legal frameworks in the
      three states examined did not lead to different decisions about providing
      treatment. More education is needed about law and its role in this area,
      particularly where law is inconsistent with traditional practice.

PMID- 29179709
TI  - Measuring inconsistency in research ethics committee review.
AB  - BACKGROUND: The review of human participant research by Research Ethics
      Committees (RECs) or Institutional Review Boards (IRBs) is a complex multi
      faceted process that cannot be reduced to an algorithm. However, this does not
      give RECs/ IRBs permission to be inconsistent in their specific requirements to
      researchers or in their final opinions. In England the Health Research Authority
      (HRA) coordinates 67 committees, and has adopted a consistency improvement plan
      including a process called "Shared Ethical Debate" (ShED) where multiple
      committees review the same project. Committee reviews are compared for
      consistency by analysing the resulting minutes. METHODS: We present a description
      of the ShED process. We report an analysis of minutes created by research ethics
      committees participating in two ShED exercises, and compare them to minutes
      produced in a published "mystery shopper" exercise. We propose a consistency
      score by defining top themes for each exercise, and calculating the ratio between
      top themes and total themes identified by each committee for each ShED exercise.
      RESULTS: Our analysis highlights qualitative differences between the ShED 19,
      ShED 20 and "mystery shopper" exercises. The quantitative measure of consistency
      showed only one committee across the three exercises with more than half its
      total themes as top themes (ratio of 0.6). The average consistency scores for the
      three exercises were 0.23 (ShED19), 0.35 (ShED20) and 0.32 (mystery shopper).
      There is a statistically significant difference between the ShED 19 exercise, and
      the ShED 20 and mystery shopper exercises. CONCLUSIONS: ShED exercises are
      effective in identifying inconsistency between ethics committees and we describe
      a scoring method that could be used to quantify this. However, whilst a level of
      inconsistency is probably inevitable in research ethics committee reviews,
      studies must move beyond the ShED methodology to understand why inconsistency
      occurs, and what an acceptable level of inconsistency might be.

PMID- 29179710
TI  - Enhancing integrated palliative care: what models are appropriate? A cross-case
      analysis.
AB  - BACKGROUND: Effective integration between hospices, palliative care services and
      other local health care services to support patients with palliative care needs
      is an important international priority. A previous model suggests that
      integration involves a cumulative stepped process of engagement with other
      organisations labelled as 'support, supplant or supplement', but the extent to
      which this model currently applies in the United Kingdom is unknown. We aimed to
      investigate accounts of hospice integration with local health care providers,
      using the framework provided by the model, to determine how service users and
      healthcare professionals perceived palliative care services and the extent of
      integration experienced. METHODS: Longitudinal organisational case study methods
      were employed using qualitative serial interviews (interval 3 months) with
      patients and family carers focusing on how services responded to their needs; and
      group interviews with health professionals. Data were audio-recorded, transcribed
      verbatim, and analysed by qualitative content analysis and combined across data
      sources. RESULTS: The study focused on four hospices in northern England,
      including 34 patients (diagnosis: 17 cancer, 10 COPD, 7 heart failure), 65%
      female, mean age 66 (range 44-89), 13 family carers of these patients (48%
      partners), and 23 health care professionals. While some care fell short of
      expectations, all patients reported high levels of satisfaction and valued
      continuity of care and efficient information sharing. All hospices supported and
      supplemented local providers, with three hospices also supplanting local
      provision by providing in-patient facilities. CONCLUSION: UK hospices
      predominantly operate in ways that support and supplement other providers. In
      addition, some also supplant local services, taking over direct responsibility
      and funding in-patient care. They all contributed to integration with local
      services, with greater blurring of boundaries than defined by the original model.
      Integrated care offers the necessary flexibility to respond to changes in patient
      needs, however, constraints from funding drivers and a lack of clear
      responsibilities in the UK can result in shortfalls in optimal service delivery.
      Integrating hospice care with local healthcare services can help to address
      demographic changes, predominantly more frail older people, and disease factors,
      including the needs of those with non-malignant conditions. This model, tested in
      the UK, could serve as an example for other countries.

PMID- 29179711
TI  - A systematic review of data mining and machine learning for air pollution
      epidemiology.
AB  - BACKGROUND: Data measuring airborne pollutants, public health and environmental
      factors are increasingly being stored and merged. These big datasets offer great
      potential, but also challenge traditional epidemiological methods. This has
      motivated the exploration of alternative methods to make predictions, find
      patterns and extract information. To this end, data mining and machine learning
      algorithms are increasingly being applied to air pollution epidemiology. METHODS:
      We conducted a systematic literature review on the application of data mining and
      machine learning methods in air pollution epidemiology. We carried out our search
      process in PubMed, the MEDLINE database and Google Scholar. Research articles
      applying data mining and machine learning methods to air pollution epidemiology
      were queried and reviewed. RESULTS: Our search queries resulted in 400 research
      articles. Our fine-grained analysis employed our inclusion/exclusion criteria to
      reduce the results to 47 articles, which we separate into three primary areas of
      interest: 1) source apportionment; 2) forecasting/prediction of air
      pollution/quality or exposure; and 3) generating hypotheses. Early applications
      had a preference for artificial neural networks. In more recent work, decision
      trees, support vector machines, k-means clustering and the APRIORI algorithm have
      been widely applied. Our survey shows that the majority of the research has been
      conducted in Europe, China and the USA, and that data mining is becoming an
      increasingly common tool in environmental health. For potential new directions,
      we have identified that deep learning and geo-spacial pattern mining are two
      burgeoning areas of data mining that have good potential for future applications
      in air pollution epidemiology. CONCLUSIONS: We carried out a systematic review
      identifying the current trends, challenges and new directions to explore in the
      application of data mining methods to air pollution epidemiology. This work shows
      that data mining is increasingly being applied in air pollution epidemiology. The
      potential to support air pollution epidemiology continues to grow with
      advancements in data mining related to temporal and geo-spacial mining, and deep
      learning. This is further supported by new sensors and storage mediums that
      enable larger, better quality data. This suggests that many more fruitful
      applications can be expected in the future.

PMID- 29179712
TI  - The costs and benefits of water fluoridation in NZ.
AB  - BACKGROUND: Implementing community water fluoridation involves costs, but these
      need to be considered against the likely benefits. We aimed to assess the cost
      benefit and cost-effectiveness of water fluoridation in New Zealand (NZ) in terms
      of expenditure and quality-adjusted life years. METHODS: Based on published
      studies, we determined the risk reduction effects of fluoridation, we quantified
      its health benefits using standardised dental indexes, and we calculated
      financial savings from averted treatment. We analysed NZ water supplies to
      estimate the financial costs of fluoridation. We devised a method to represent
      dental caries experience in quality-adjusted life years. RESULTS: Over 20 years,
      the net discounted saving from adding fluoride to reticulated water supplies
      supplying populations over 500 would be NZ$1401 million, a nine times pay-off.
      Between 8800 and 13,700 quality-adjusted life years would be gained. While
      fluoridating reticulated water supplies for large communities is cost-effective,
      it is unlikely to be so with populations smaller than 500. CONCLUSIONS: Community
      water fluoridation remains highly cost-effective for all but very small
      communities. The health benefits-while (on average) small per person-add up to a
      substantial reduction in the national disease burden across all ethnic and
      socioeconomic groups.

PMID- 29179713
TI  - Analysis of the characteristics of cracked teeth and evaluation of pulp status
      according to periodontal probing depth.
AB  - BACKGROUND: The purpose of this study was to analyze the characteristics of
      cracked teeth and to evaluate pulp status according to periodontal probing depth
      (PPD). METHODS: A total of 182 cracked teeth were included. The location and type
      of the cracked teeth, age and gender of the patients, restoration type, pulp
      status, PPD, and radiographic findings were analyzed. RESULTS: Mandibular second
      molars (25.3%) were the most frequently involved teeth, followed by mandibular
      first molars (22.5%), maxillary first molars (22.0%), and maxillary second molars
      (17.6%). The patient age was most frequently 50-59 years. Cracks occurred mainly
      in nonbonded restorations, such as gold (26.9%), and were usually found in intact
      teeth (37.9%). A total of 103 teeth (56.6%) had an initial PPD of less than 3 mm,
      while 40 (22.0%) had a PPD of 4-6 mm, and 39 (21.4%) had PPD of 7 mm or more. A
      total of 33 cracked teeth (18.1%) were diagnosed with pulp necrosis, 40 (22.0%)
      with irreversible pulpitis, and 97 (53.3%) with reversible pulpitis. The
      incidence of pulp necrosis was 31.8% among cracked teeth with a PPD of 4-6 mm,
      and 28.6% among those with a PPD of 7 mm or more. CONCLUSIONS: Cracks occurred
      mainly in molar teeth, and were commonly found in intact teeth with no
      restoration. Patients with cracked teeth were most frequently aged 50-59 years.
      Cracked teeth showing a PPD of more than 4 mm were more likely to show pulp
      necrosis.

PMID- 29179715
TI  - The role of health policy in the burden of breast cancer in Brazil.
AB  - BACKGROUND: Breast cancer affects millions of women worldwide, particularly in
      Brazil, where public healthcare system is an important model in health
      organization and the cost of chronic disease has affected the economy in the
      first decade of the twenty-first century. The aim was to evaluate the role of
      health policy in the burden of breast cancer in Brazil between 2004 and 2014.
      METHODS: Secondary analysis was performed in 2017 with Brazilian Health Ministry
      official data, extracted from the Department of Informatics of the National
      Health System. Age-standardized mortality and the age-standardized incidence of
      hospital admission by breast cancer were calculated per 100,000 people. Public
      healthcare costs were converted to US dollars. Regression analysis was performed
      to estimate the trend of breast cancer rates and healthcare costs, and principal
      component analysis was performed to estimate a cost factor. Stata(r) 11.0 was
      utilized. RESULTS: Between 2004 to 2014, the age-standardized rates of breast
      cancer mortality and the incidence of hospital admission and public healthcare
      costs increased. There was a positive correlation between breast cancer and
      healthcare public costs, mainly influenced by governmental strategies.
      CONCLUSIONS: Governmental strategies are effective against the burden of breast
      cancer in Brazil.

PMID- 29179714
TI  - Influence of age, gender, and radiographic features on the deltoid splitting
      approach for surgical osteosynthesis in displaced proximal humerus fractures: a
      comparison study.
AB  - BACKGROUND: The deltoid splitting approach has recently been widely adopted to
      facilitate less invasive procedures for proximal humerus fractures. However,
      there are still concerns regarding its effectiveness in aging people and in cases
      involving complex fractures. This study was conducted to evaluate the efficacy of
      a proximal humeral locking plate using the anterolateral deltoid splitting
      approach and to specifically examine the effect of patient age, gender, and
      fracture pattern on surgical outcomes. METHODS: Forty-two cases of proximal
      humeral fractures treated using the deltoid splitting approach and locking plate
      fixation were reviewed. Outcome differences were evaluated in terms of age,
      gender distribution, and radiographic analysis based on the Neer Classification.
      The influence of the surgical approach was further investigated by age-matched
      paired analysis after subdividing patients into two age groups (younger than 60
      years vs. older than 60 years; N = 21, in each group). RESULTS: In total, 41
      patients (98%) demonstrated fracture union. The average Constant score was 80.4.
      No significant differences were found between patients younger than 60 years, and
      the older patients. Higher mean scores were found in men than in women (p =
      0.448) and in simple fractures than in complex fractures (p = 0.454), without any
      significant differences. Better postoperative functional outcomes were observed
      when the humeral head-neck angle was greater than 105 degrees , with a
      significant difference (p = 0.000). Surgical complications were found in 16
      patients (38%) without significant difference between two age groups (p = 0.268).
      The most common complication was screw penetration. CONCLUSIONS: Anterolateral
      deltoid splitting using locking plate fixation provided a feasible alternative
      for surgery of proximal humerus fractures in different age groups and yielded
      comparable outcomes when the neck-shaft angle was properly restored. Surgeons
      must be cautious regarding potential complications, especially with screw
      penetration when using the locking plate through a less invasive approach. TRIAL
      REGISTRATION: ISRCTN75494532 . Trial Date: 2017/01/31.

PMID- 29179716
TI  - Patient perspectives on engagement in decision-making in early management of non
      ST elevation acute coronary syndrome: a qualitative study.
AB  - BACKGROUND: Surveys of patients suggest many want to be actively involved in
      treatment decisions for acute coronary syndromes. However, patient experiences of
      their engagement and participation in early phase decision-making have not been
      well described. METHODS: We performed a patient led qualitative study to explore
      patient experiences with decision-making processes when admitted to hospital with
      non-ST elevation acute coronary syndrome. Trained patient-researchers conducted
      the study via a three-phase approach using focus groups and semi-structured
      interviews and employing grounded theory methodology. RESULTS: Twenty patients
      discharged within one year of a non-ST elevation acute coronary syndrome
      participated in the study. Several common themes emerged. First, patients
      characterized the admission and early treatment of ACS as a rapidly unfolding
      process where they had little control. Participants felt they played a passive
      role in early phase decision-making. Furthermore, participants described feeling
      reduced capacity for decision-making owing to fear and mental stress from acute
      illness, and therefore most but not all participants were relieved that expert
      clinicians made decisions for them. Finally, once past the emergent phase of
      care, participants wanted to retake a more active role in their treatment and
      follow-up plans. CONCLUSIONS: Patients admitted with ACS often do not take an
      active role in initial clinical decisions, and are satisfied to allow the medical
      team to direct early phase care. These results provide important insight relevant
      to designing patient-centered interventions in ACS and other urgent care
      situations.

PMID- 29179717
TI  - Does having a usual primary care provider reduce patient self-referrals in rural
      China's rural multi-tiered medical system? A retrospective study in Qianjiang
      District, China.
AB  - INTRODUCTION: Within China's multi-tiered medical system, many patients seek care
      in higher-tiered hospitals without a referral by a primary-care provider. This
      trend, generally referred to as patient self-referral behavior, may reduce the
      efficiency of the health care system. This study seeks to test the hypothesis
      that having a usual primary care provider could reduce patients' self-referral
      behavior. METHODS: We obtained medical records of 832 patients who were
      hospitalized for common respiratory diseases from township hospitals in Qianjiang
      District of Chongqing City during 2012-2014. Logit regressions were performed to
      examine the association between having a township hospital as a usual provider
      and self-referring to a county hospital after being discharged from a township
      hospital, while controlling for patients' gender, age, income, education,
      severity of disease, distance to the nearest county hospital and the general
      quality of the township hospitals in their community. A propensity score
      weighting approach was applied. RESULTS: We found that having a usual primary
      care provider was associated with a lower likelihood of self-referral (odds ratio
      = 0.58, 95% confidence interval [CI] =0.41-0.82), and a 9% (95% CI: -14%, - 3%)
      reduction in the probability of patients' self-referral behavior.
      DISCUSSION/CONCLUSION: The results suggest that establishing a long-term
      relationship between patients and primary care providers may enhance the patient
      physician relationship and reduce patients' tendency for unnecessary use of
      medical resources.

PMID- 29179718
TI  - What is the impact of a clinically related readmission measure on the assessment
      of hospital performance?
AB  - BACKGROUND: The Hospital Readmission Reduction Program (HRRP) penalizes hospitals
      for high all-cause unplanned readmission rates. Many have expressed concern that
      hospitals serving patient populations with more comorbidities, lower incomes, and
      worse self-reported health status may be disproportionately penalized by
      readmissions that are not clinically related to the index admission. The impact
      of including clinically unrelated readmissions on hospital performance is largely
      unknown. We sought to determine if a clinically related readmission measure would
      significantly alter the assessment of hospital performance. METHODS: We analyzed
      Medicare claims for beneficiaries in Michigan admitted for pneumonia and joint
      replacement from 2011 to 2013. We compared each hospital's 30-day readmission
      rate using specifications from the HRRP's all-cause unplanned readmission measure
      to values calculated using a clinically related readmission measure. RESULTS: We
      found that the mean 30-day readmission rates were lower when calculated using the
      clinically related readmission measure (joint replacement: all-cause 5.8%,
      clinically related 4.9%, p < 0.001; pneumonia: all cause 12.5%, clinically
      related 11.3%, p < 0.001)). The correlation of hospital ranks using both methods
      was strong (joint replacement: 0.95 (p < 0.001), pneumonia: 0.90 (p < 0.001)).
      CONCLUSIONS: Our findings suggest that, while greater specificity may be achieved
      with a clinically related measure, clinically unrelated readmissions may not
      impact hospital performance in the HRRP.

PMID- 29179719
TI  - Effect of dendritic cell-cytokine-induced killer cells in patients with advanced
      colorectal cancer combined with first-line treatment.
AB  - BACKGROUND: Surgical resection combined with adjuvant chemotherapy is considered
      as the gold-standard treatment for advanced colorectal cancer patients. These
      patients have a poor 5-year survival rate of 5% or less. Furthermore, a large
      dose of chemotherapy can produce adverse side effects and severe toxicity.
      Therefore, this retrospective study aimed to evaluate the efficacy of dendritic
      cell-cytokine-induced killer (DC-CIK) cell infusion as an adjuvant therapy in
      patients with advanced colorectal cancer combined with first-line treatment.
      METHODS: A total of 142 patients with stage III/IV colorectal carcinoma who had
      been treated with first-line therapy were included in this study. Among these
      patients, 71 patients received first-line treatment only (non-DC-CIK group),
      while the other 71 patients who had similar demographic and clinical
      characteristics received a DC-CIK cell infusion combined with first-line
      treatment (DC-CIK group). These patients were followed up until August 2014. Data
      were analyzed by Kaplan-Meier and Cox regression. RESULTS: Our results showed
      that the 5-year overall survival (OS) rate for the DC-CIK group versus the non-DC
      CIK group was 41.3 versus 19.4% (p = 0.001) and the 5-year progression-free
      survival (PFS) rate for the DC-CIK group versus the non-DC-CIK group was 57.4
      versus 33.6% (p = 0.022). CONCLUSIONS: Our results showed that patients with
      advanced colorectal cancer might benefit from DC-CIK immunotherapy combined with
      first-line therapy by significantly prolonging 5-year OS and PFS.

PMID- 29179720
TI  - Depression comorbid with tuberculosis and its impact on health status: cross
      sectional analysis of community-based data from 48 low- and middle-income
      countries.
AB  - BACKGROUND: Depression in tuberculosis increases the risk for adverse health
      outcomes. However, little is known about comorbid depression and tuberculosis in
      the general population. Thus, we assessed the association between depression and
      tuberculosis, and the decrements in health status associated with this
      comorbidity in 48 low- and middle-income countries. METHODS: Cross-sectional,
      community-based data from the World Health Survey on 242,952 individuals aged >=
      18 years were analyzed. Based on the World Mental Health Survey version of the
      Composite International Diagnostic Interview, past 12-month depression was
      categorized into depressive episode, brief depressive episode, subsyndromal
      depression, and no depression. Health status across six domains (cognition,
      interpersonal activities, sleep/energy, self-care, mobility, pain/discomfort) was
      assessed. Multivariable logistic and linear regression analyses were performed to
      assess the associations. RESULTS: The prevalence of depressive episode among
      those with and without tuberculosis was 23.7% and 6.8%, respectively (P < 0.001).
      Tuberculosis was associated with a 1.98 (95% CI 1.47-2.67), 1.75 (95% CI 1.26
      2.42), and 3.68 (95% CI 3.01-4.50) times higher odds for subsyndromal depression,
      brief depressive episode, and depressive episode, respectively. Depressive
      episode co-occurring with tuberculosis was associated with significantly worse
      health status across all six domains compared to tuberculosis alone. Interaction
      analysis showed that depression significantly amplifies the association between
      TB and difficulties in self-care but not in other health domains. CONCLUSIONS:
      Depression is highly prevalent in adults with tuberculosis, and is associated
      with worse health status compared to tuberculosis without depression. Public
      health efforts directed to the recognition and management of depression in people
      with tuberculosis may lead to better outcomes.

PMID- 29179721
TI  - Apigenin, by activating p53 and inhibiting STAT3, modulates the balance between
      pro-apoptotic and pro-survival pathways to induce PEL cell death.
AB  - BACKGROUND: Apigenin is a flavonoid widely distributed in plant kingdom that
      exerts cytotoxic effects against a variety of solid and haematological cancers.
      In this study, we investigated the effect of apigenin against primary effusion
      lymphoma (PEL), a KSHV-associated B cell lymphoma characterized by a very
      aggressive behavior, displaying constitutive activation of STAT3 as well as of
      other oncogenic pathways and harboring wtp53. METHODS: Cell death was assessed by
      trypan blue exclusion assay, FACS analysis as well as by biochemical studies. The
      latter were also utilized to detect the occurrence of autophagy and the molecular
      mechanisms leading to the activation of both processes by apigenin. FACS analysis
      was used to measure the intracellular ROS utilizing DCFDA. RESULTS: We show that
      apigenin induced PEL cell death and autophagy along with reduction of
      intracellular ROS. Mechanistically, apigenin activated p53 that induced catalase,
      a ROS scavenger enzyme, and inhibited STAT3, the most important pro-survival
      pathway in PEL, as assessed by p53 silencing. On the other hand, STAT3 inhibition
      by apigenin resulted in p53 activation, since STAT3 negatively influences p53
      activity, highlighting a regulatory loop between these two pathways that
      modulates PEL cell death/survival. CONCLUSION: The findings of this study
      demonstrate that apigenin may modulate pro-apoptotic and pro-survival pathways
      representing a valid therapeutic strategy against PEL.

PMID- 29179722
TI  - Aminoglucose-functionalized, redox-responsive polymer nanomicelles for overcoming
      chemoresistance in lung cancer cells.
AB  - BACKGROUND: Chemotherapeutic drugs used for cancer therapy frequently encounter
      multiple-drug resistance (MDR). Nanoscale carriers that can target tumors to
      accumulate and release drugs intracellularly have the greatest potential for
      overcoming MDR. Glucose transporter-1 (GLUT-1) and glutathione (GSH)
      overexpression in cancer cells was exploited to assemble aminoglucose (AG)
      conjugated, redox-responsive nanomicelles from a single disulfide bond-bridged
      block polymer of polyethylene glycol and polylactic acid (AG-PEG-SS-PLA).
      However, whether this dual functional vector can overcome MDR in lung cancer is
      unknown. RESULTS: In this experiment, AG-PEG-SS-PLA was synthetized successfully,
      and paclitaxel (PTX)-loaded AG-PEG-SS-PLA (AG-PEG-SS-PLA/PTX) nanomicelles
      exhibited excellent physical properties. These nanomicelles show enhanced tumor
      targeting as well as drug accumulation and retention in MDR cancer cells.
      Caveolin-dependent endocytosis is mainly responsible for nanomicelle
      internalization. After internalization, the disulfide bond of AG-PEG-SS-PLA is
      cleaved in the presence of high intracellular glutathione levels, causing the
      hydrophobic core to become a polar aqueous solution, which subsequently results
      in nanomicelle disassembly and the rapid release of encapsulated PTX. Reduced
      drug resistance was observed in cancer cells in vitro. The caspase-9 and caspase
      3 cascade was activated by the AG-PEG-SS-PLA/PTX nanomicelles through
      upregulation of the pro-apoptotic proteins Bax and Bid and suppression of the
      anti-apoptotic protein Bcl-2, thereby increasing apoptosis. Furthermore,
      significantly enhanced tumor growth inhibition was observed in nude mice bearing
      A549/ADR xenograft tumors after the administration of AG-PEG-SS-PLA/PTX
      nanomicelles via tail injection. CONCLUSIONS: These promising results indicate
      that AG-PEG-SS-PLA/PTX nanomicelles could provide the foundation for a paradigm
      shift in MDR cancer therapy.

PMID- 29179724
TI  - Intervention fidelity in the definitive cluster randomised controlled trial of
      the Healthy Lifestyles Programme (HeLP) trial: findings from the process
      evaluation.
AB  - BACKGROUND: The Healthy Lifestyles Programme (HeLP) was a novel school-located
      intervention for 9-10 year olds, designed to prevent obesity by changing patterns
      of child behaviour through the creation of supportive school and home
      environments using dynamic and creative delivery methods. This paper reports on
      both the quantitative and qualitative data regarding the implementation of the
      HeLP intervention in the definitive cluster randomised controlled trial, which
      was part of the wider process evaluation. METHODS: Mixed methods were used to
      collect data on intervention uptake, fidelity of delivery in terms of content and
      quality of delivery of the intervention, as well as school and child engagement
      with the programme. Data were collected using registers of attendance,
      observations and checklists, field notes, focus groups with children and semi
      structured interviews with teachers. Qualitative data were analysed thematically
      and quantitative data were summarized using descriptive statistics. RESULTS: All
      16 intervention schools received a complete or near complete programme (94-100%),
      which was delivered in the spirit in which it had been designed. Of the 676
      children in the intervention schools, over 90% of children participated in each
      phase of HeLP; 92% of children across the socio-economic spectrum were deemed to
      be engaged with HeLP and qualitative data revealed a high level of enjoyment by
      all children, particularly to the interactive drama workshops. Further evidence
      of child engagment with the programme was demonstrated by children's clear
      understanding of programme messages around marketing, moderation and food
      labelling. Thirteen of the intervention schools were deemed to be fully engaged
      with HeLP and qualitative data revealed a high level of teacher 'buy in', due to
      the programme's compatability with the National Curriculum, level of teacher
      support and use of innovative and creative delivery methods by external drama
      practitioners. CONCLUSION: Our trial shows that it is possible to successfully
      scale up complex school-based interventions, engage schools and children across
      the socio-economic spectrum and deliver an intervention as designed. As programme
      integrity was maintained throughout the HeLP trial, across all intervention
      schools, we can be confident that the trial findings are a true reflection of the
      effectiveness of the intervention, enabling policy recommendations to be made.
      TRIAL REGISTRATION: ISRCTN15811706.

PMID- 29179723
TI  - Novel pathomechanisms in inflammatory neuropathies.
AB  - Inflammatory neuropathies are rare autoimmune-mediated disorders affecting the
      peripheral nervous system. Considerable progress has recently been made in
      understanding pathomechanisms of these disorders which will be essential for
      developing novel diagnostic and therapeutic strategies in the future. Here, we
      summarize our current understanding of antigenic targets and the relevance of new
      immunological concepts for inflammatory neuropathies. In addition, we provide an
      overview of available animal models of acute and chronic variants and how new
      diagnostic tools such as magnetic resonance imaging and novel therapeutic
      candidates will benefit patients with inflammatory neuropathies in the future.
      This review thus illustrates the gap between pre-clinical and clinical findings
      and aims to outline future directions of development.

PMID- 29179725
TI  - High resolution chromosomal microarray analysis in paediatric obsessive
      compulsive disorder.
AB  - BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a common and chronic disorder
      in which a person has uncontrollable, reoccurring thoughts and behaviours. It is
      a complex genetic condition and, in case of early onset (EO), the patients
      manifest a more severe phenotype, and an increased heritability. Large (>500 kb)
      copy number variations (CNVs) previously associated with autism and schizophrenia
      have been reported in OCD. Recently, rare CNVs smaller than 500 kb overlapping
      risk loci for other neurodevelopmental conditions have also been reported in OCD,
      stressing the importance of examining CNVs of any size range. The aim of this
      study was to further investigate the role of rare and small CNVs in the aetiology
      of EO-OCD. METHODS: We performed high-resolution chromosomal microarray analysis
      in 121 paediatric OCD patients and in 124 random controls to identify rare CNVs
      (>50 kb) which might contribute to EO-OCD. RESULTS: The frequencies and the size
      of the observed rare CNVs in the patients did not differ from the controls.
      However, we observed a significantly higher frequency of rare CNVs affecting
      brain related genes, especially deletions, in the patients (OR = 1.98, 95% CI
      1.02-3.84; OR = 3.61, 95% CI 1.14-11.41, respectively). Similarly, enrichment
      analysis of CNVs gene content, performed with three independent methods,
      confirmed significant clustering of predefined genes involved in synaptic/brain
      related functional pathways in the patients but not in the controls. In two
      patients we detected de-novo CNVs encompassing genes previously associated with
      different neurodevelopmental disorders (NRXN1, ANKS1B, UHRF1BP1). CONCLUSIONS:
      Our results further strengthen the role of small rare CNVs, particularly
      deletions, as susceptibility factors for paediatric OCD.

PMID- 29179726
TI  - Modulation of the functional association between the HIV-1 intasome and the
      nucleosome by histone amino-terminal tails.
AB  - BACKGROUND: Stable insertion of the retroviral DNA genome into host chromatin
      requires the functional association between the intasome (integrase.viral DNA
      complex) and the nucleosome. The data from the literature suggest that direct
      protein-protein contacts between integrase and histones may be involved in
      anchoring the intasome to the nucleosome. Since histone tails are candidates for
      interactions with the incoming intasomes we have investigated whether they could
      participate in modulating the nucleosomal integration process. RESULTS: We show
      here that histone tails are required for an optimal association between HIV-1
      integrase (IN) and the nucleosome for efficient integration. We also demonstrate
      direct interactions between IN and the amino-terminal tail of human histone H4 in
      vitro. Structure/function studies enabled us to identify amino acids in the
      carboxy-terminal domain of IN that are important for this interaction. Analysis
      of the nucleosome-binding properties of catalytically active mutated INs
      confirmed that their ability to engage the nucleosome for integration in vitro
      was affected. Pseudovirus particles bearing mutations that affect the IN/H4
      association also showed impaired replication capacity due to altered integration
      and re-targeting of their insertion sites toward dynamic regions of the chromatin
      with lower nucleosome occupancy. CONCLUSIONS: Collectively, our data support a
      functional association between HIV-1 IN and histone tails that promotes anchoring
      of the intasome to nucleosomes and optimal integration into chromatin.

PMID- 29179728
TI  - Site-specific selection reveals selective constraints and functionality of tumor
      somatic mtDNA mutations.
AB  - BACKGROUND: Previous studies have indicated that tumor mitochondrial DNA (mtDNA)
      mutations are primarily shaped by relaxed negative selection, which is
      contradictory to the critical roles of mtDNA mutations in tumorigenesis.
      Therefore, we hypothesized that site-specific selection may influence tumor mtDNA
      mutations. METHODS: To test our hypothesis, we developed the largest collection
      of tumor mtDNA mutations to date and evaluated how natural selection shaped mtDNA
      mutation patterns. RESULTS: Our data demonstrated that both positive and negative
      selections acted on specific positions or functional units of tumor mtDNAs,
      although the landscape of these mutations was consistent with the relaxation of
      negative selection. In particular, mutation rate (mutation number in a
      region/region bp length) in complex V and tRNA coding regions, especially in ATP8
      within complex V and in loop and variable regions within tRNA, were significantly
      lower than those in other regions. While the mutation rate of most codons and
      amino acids were consistent with the expectation under neutrality, several codons
      and amino acids had significantly different rates. Moreover, the mutations under
      selection were enriched for changes that are predicted to be deleterious, further
      supporting the evolutionary constraints on these regions. CONCLUSION: These
      results indicate the existence of site-specific selection and imply the important
      role of the mtDNA mutations at some specific sites in tumor development.

PMID- 29179727
TI  - Mild endoplasmic reticulum stress ameliorates lipopolysaccharide-induced
      neuroinflammation and cognitive impairment via regulation of microglial
      polarization.
AB  - BACKGROUND: Neuroinflammation, which ultimately leads to neuronal loss, is
      considered to play a crucial role in numerous neurodegenerative diseases. The
      neuroinflammatory process is characterized by the activation of glial cells such
      as microglia. Endoplasmic reticulum (ER) stress is commonly associated with
      impairments in neuronal function and cognition, but its relationship and role in
      neurodegeneration is still controversial. Recently, it was confirmed that
      nonharmful levels of ER stress protected against experimental Parkinson's
      disease. Here, we investigated mild ER stress-based regulation of
      lipopolysaccharide (LPS)-driven neuroinflammation in rats and in primary
      microglia. METHODS: Male Sprague-Dawley (SD) rats received the
      intracerebroventricular injection of the ER stress activator tunicamycin (TM)
      with or without intraperitoneal injection of the ER stress stabilizer sodium 4
      phenylbutyrate (4-PBA) 1 h before LPS administration. The levels of
      neuroinflammation and memory dysfunction were assessed 24 h after treatment. In
      addition, the effect of mild ER stress on microglia was determined in vitro.
      RESULTS: Here, we found that low doses of TM led to mild ER stress without cell
      or organism lethality. We showed that mild ER stress preconditioning reduced
      microglia activation and neuronal death as well as improved LPS-induced memory
      impairment in rats. In addition, pre-exposure to nonlethal doses of TM in
      microglia showed significant protection against LPS-induced proinflammatory
      cytokine production and M1/2b polarization. However, sodium 4-PBA, a compound
      that ameliorates ER stress, ablated this protective effect in vivo and in vitro.
      CONCLUSIONS: Based on our findings, we conclude that the mild ER stress not only
      limits the accumulation of misfolded proteins but also protects tissues from
      harmful endotoxemia insults. Therefore, ER stress preconditioning has potential
      therapeutic value for the treatment of neurodegenerative diseases.

PMID- 29179729
TI  - Deficiency of innate-like T lymphocytes in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Based on the phenotypic and functional characteristics unconventional
      T-lymphocytes such as invariant natural killer T (iNKT) cells and mucosal
      associated invariant T (MAIT) cells link the innate and adaptive immune
      responses. Up to now data are scarce about their involvement in pulmonary
      disorders including chronic obstructive pulmonary disease (COPD). This study
      explores simultaneously the frequencies of iNKT and MAIT cells in the peripheral
      blood and sputum of stable and exacerbating COPD patients. METHODS: By means of
      multicolor flow cytometry frequencies of total iNKT and MAIT cells and their
      subsets were enumerated in peripheral blood and sputum samples of healthy
      controls, and COPD patients. In addition, gene expression of TCR for iNKT, MAIT
      cells, and CD1d, MR1 were assessed by qPCR in the study cohorts. RESULTS:
      Percentages of total iNKT and MAIT cells were dramatically dropped in blood, and
      reduced numbers of iNKT cells were observed in the sputum of COPD patients.
      Furthermore decreased DN and increased CD4+ iNKT subsets, while increased DN and
      decreased CD8+ MAIT subpopulations were measured in the blood of COPD patients.
      Reduced invariant TCR mRNA levels in COPD patients had confirmed these previous
      findings. The mRNA expression of CD1d and MR1 were increased in stable and
      exacerbating COPD patients; however both molecules were decreased upon antibiotic
      and systemic steroid treatments. CONCLUSIONS: Our results support the notion that
      both invariant T-cell populations are affected in COPD. Further detailed analysis
      of invariant T cells could shed more light into the complex interactions of these
      lymphocyte groups in COPD pathogenesis.

PMID- 29179730
TI  - Control under times of uncertainty: the relationship between hospital competition
      and physician-patient disputes.
AB  - BACKGROUND: Recently, cases of medical disputes and even acts of violence toward
      physicians by patients in China have been escalating. It remains unknown whether
      competition improves the patient-physician relationship. METHODS: This paper
      analyzes the relationship between hospital competition and the probability of
      medical disputes occurrence according to the theory of social control. Data from
      all hospitals in the Sichuan province of China from 2011 to 2014 were included in
      the study. The fixed radius approach with GIS information was employed to define
      hospital market, and the differences in competition over time and across regions
      were utilized. Our analysis is based on the fixed effect estimation, which
      accounts for the time-invariant unobserved heterogeneity among hospitals.
      RESULTS: We found an inversed U-shaped relationship between HHI and the
      likelihood of medical disputes. As beneath either situation of monopoly or full
      competition, the burst of physician-patient dispute was downward into a valley,
      but it rises and then falls again with the increase of HHI, it reached the peak
      at the typical semi-market hospital competition structure. CONCLUSIONS: Our
      results highlight the probability of change in disputes occurrence with the
      transition of hospital competition and its psychological explanation, providing
      implications for China's future health reform.

PMID- 29179731
TI  - Can routine data be used to support cancer clinical trials? A historical baseline
      on which to build: retrospective linkage of data from the TACT (CRUK 01/001)
      breast cancer trial and the National Cancer Data Repository.
AB  - BACKGROUND: Randomised clinical trials (RCTs) are the gold standard for
      evaluating new cancer treatments. They are, however, expensive to conduct,
      particularly where long-term follow-up of participants is required. Tracking
      participants via routine datasets could provide a cost-effective alternative for
      ascertaining follow-up information required to evaluate disease outcomes. This
      project explores the potential for routine data to inform cancer trials, using,
      the historical National Cancer Data Repository (NCDR) for English NHS sites and,
      for validation, mature data available from the TACT trial. METHODS: Datasets were
      matched using patients' NHS number, date of birth (dob) and name/initials.
      Demographics, clinical characteristics and outcomes were assessed for agreement
      and completeness. Overall survival was compared between NCDR and TACT. RESULTS: A
      total of 3151 patients underwent linkage; 3047 (96.7%) of which had matched
      records. Extensive cleaning was required for some registry data fields, e.g.
      cause of death, whilst others had large amounts of missing data, e.g. tumour size
      (22.1%). Other data had high levels of matching such as dob (99.6%) and date of
      death (89.6%). There was no evidence of differential survival rates (8-year
      survival: TACT = 75% (95% CI 73, 76); NCDR = 76% (95% CI 74, 77)). CONCLUSIONS:
      Data quality and completeness requires improvement before routine data could be
      used for RCTs. Introduction of new routine datasets, including COSD, is welcomed
      although reporting of disease-recurrence events remains a concern. Prospective
      validation of such datasets is required before RCTs can confidently switch
      patient follow-up to utilise routinely collected NHS-based data. TACT TRIAL
      REGISTRATION: Clinicaltrials.gov NCT00033683 , registered on 9 April 2002;
      ISRCTN79718493 , registered on 1 July 2001.

PMID- 29179733
TI  - A comparison of results of empirical studies of supplementary search techniques
      and recommendations in review methodology handbooks: a methodological review.
AB  - BACKGROUND: The purpose and contribution of supplementary search methods in
      systematic reviews is increasingly acknowledged. Numerous studies have
      demonstrated their potential in identifying studies or study data that would have
      been missed by bibliographic database searching alone. What is less certain is
      how supplementary search methods actually work, how they are applied, and the
      consequent advantages, disadvantages and resource implications of each search
      method. The aim of this study is to compare current practice in using
      supplementary search methods with methodological guidance. METHODS: Four
      methodological handbooks in informing systematic review practice in the UK were
      read and audited to establish current methodological guidance. Studies evaluating
      the use of supplementary search methods were identified by searching five
      bibliographic databases. Studies were included if they (1) reported practical
      application of a supplementary search method (descriptive) or (2) examined the
      utility of a supplementary search method (analytical) or (3) identified/explored
      factors that impact on the utility of a supplementary method, when applied in
      practice. RESULTS: Thirty-five studies were included in this review in addition
      to the four methodological handbooks. Studies were published between 1989 and
      2016, and dates of publication of the handbooks ranged from 1994 to 2014. Five
      supplementary search methods were reviewed: contacting study authors, citation
      chasing, handsearching, searching trial registers and web searching. CONCLUSIONS:
      There is reasonable consistency between recommended best practice (handbooks) and
      current practice (methodological studies) as it relates to the application of
      supplementary search methods. The methodological studies provide useful
      information on the effectiveness of the supplementary search methods, often
      seeking to evaluate aspects of the method to improve effectiveness or efficiency.
      In this way, the studies advance the understanding of the supplementary search
      methods. Further research is required, however, so that a rational choice can be
      made about which supplementary search strategies should be used, and when.

PMID- 29179732
TI  - Drug repurposing for the treatment of glioblastoma multiforme.
AB  - BACKGROUND: Glioblastoma Multiforme is the deadliest type of brain tumor and is
      characterized by very poor prognosis with a limited overall survival. Current
      optimal therapeutic approach has essentially remained unchanged for more than a
      decade, consisting in maximal surgical resection followed by radiotherapy plus
      temozolomide. MAIN BODY: Such a dismal patient outcome represents a compelling
      need for innovative and effective therapeutic approaches. Given the development
      of new drugs is a process presently characterized by an immense increase in costs
      and development time, drug repositioning, finding new uses for existing approved
      drugs or drug repurposing, re-use of old drugs when novel molecular findings make
      them attractive again, are gaining significance in clinical pharmacology, since
      it allows faster and less expensive delivery of potentially useful drugs from the
      bench to the bedside. This is quite evident in glioblastoma, where a number of
      old drugs is now considered for clinical use, often in association with the first
      line therapeutic intervention. Interestingly, most of these medications are, or
      have been, widely employed for decades in non-neoplastic pathologies without
      relevant side effects. Now, the refinement of their molecular mechanism(s) of
      action through up-to-date technologies is paving the way for their use in the
      therapeutic approach of glioblastoma as well as other cancer types. SHORT
      CONCLUSION: The spiraling costs of new antineoplastic drugs and the long time
      required for them to reach the market demands a profoundly different approach to
      keep lifesaving therapies affordable for cancer patients. In this context,
      repurposing can represent a relatively inexpensive, safe and fast approach to
      glioblastoma treatment. To this end, pros and cons must be accurately considered.

PMID- 29179734
TI  - An integrated digital/clinical approach to smoking cessation in lung cancer
      screening: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Delivering effective tobacco dependence treatment that is feasible
      within lung cancer screening (LCS) programs is crucial for realizing the health
      benefits and cost savings of screening. Large-scale trials and systematic reviews
      have demonstrated that digital cessation interventions (i.e. web-based and text
      message) are effective, sustainable over the long-term, scalable, and cost
      efficient. Use of digital technologies is commonplace among older adults, making
      this a feasible approach within LCS programs. Use of cessation treatment has been
      improved with models that proactively connect smokers to treatment rather than
      passive referrals. Proactive referral to cessation treatment has been advanced
      through healthcare systems changes such as modifying the electronic health record
      to automatically link smokers to treatment. METHODS: This study evaluates the
      impact of a proactive enrollment strategy that links LCS-eligible smokers with an
      evidence-based intervention comprised of a web-based (WEB) program and integrated
      text messaging (TXT) in a three-arm randomized trial with repeated measures at
      one, three, six, and 12 months post randomization. The primary outcome is
      biochemically confirmed abstinence at 12 months post randomization. We will
      randomize 1650 smokers who present for a clinical LCS to: (1) a usual care
      control condition (UC) which consists of Ask-Advise-Refer; (2) a digital (WEB +
      TXT) cessation intervention; or (3) a digital cessation intervention combined
      with tobacco treatment specialist (TTS) counseling (WEB + TXT + TTS). DISCUSSION:
      The scalability and sustainability of a digital intervention may represent the
      most cost-effective and feasible approach for LCS programs to proactively engage
      large numbers of smokers in effective cessation treatment. We will also evaluate
      the impact and cost-effectiveness of adding proven clinical intervention provided
      by a TTS. We expect that a combined digital/clinical intervention will yield
      higher quit rates than digital alone, but that it may not be as cost-effective or
      feasible for LCS programs to implement. This study is innovative in its use of
      interoperable, digital technologies to deliver a sustainable, scalable, high
      impact cessation intervention and to facilitate its integration within clinical
      practice. It will add to the growing knowledge base about the overall
      effectiveness of digital interventions and their role in the healthcare delivery
      system. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03084835 . Registered on 9
      March 2017.

PMID- 29179735
TI  - Ficus sycomorus extract reversed behavioral impairment and brain oxidative stress
      induced by unpredictable chronic mild stress in rats.
AB  - BACKGROUND: Stress, regardless of its nature is nowadays recognized as one of the
      major risk factors for neuropsychiatric diseases, such as mood and anxiety
      disorders. The brain compared with other organs is more vulnerable to oxidative
      damage mainly due to its high rate of oxygen consumption, abundant lipid content,
      and relative insufficiency of antioxidant enzymes. Thus, the identification of
      neural mechanisms underlying resistance and vulnerability to stress is of crucial
      importance in understanding the pathophysiology of neuropsychiatric disorders and
      in developing new treatments, since the existing ones are for several reasons
      subject to increasing limitations. This study was aimed to assess the effects of
      hydromethanolic extract of Ficus sycomorus stem bark on depression, anxiety and
      memory impairment induced by unpredictable chronic mild stress (UCMS) in rats.
      METHODS: These effects were studied using anxiety-related behavior, depression
      related behavior, anhedonia-like behavior and the Y maze task. Sucrose test was
      performed twice (before and after UCMS) to assess anhedonia in rats. Liquid
      chromatography-mass spectrometry analysis of the extract were performed. The
      antioxidant activities of the extract were assessed using total glutathione (GSH)
      content and malondialdehyde (MDA) level (lipid peroxidation) in the rat temporal
      lobe homogenates. RESULTS: The extract of F. sycomorus in a dose of 100 mg/kg
      significantly increased the sucrose consumption and the swimming time which had
      been reduced by the unpredictable chronic mild stress (p < 0.001). The extract
      also significantly reduced (p < 0.01) the latency time in the novelty-suppressed
      feeding test. In the elevated plus-maze, the extract (100 and 200 mg/kg)
      significantly reduced (p < 0.01) the time and the number of entries into the
      closed arms. The treatment with the extracts also significantly increased
      alternation in the Y-maze (p < 0.01 for 100 mg/kg). The extract significantly
      increased the total GSH content and reduced MDA level in rat temporal lobe. For
      the LC-MS analysis, the major compound in the extract was a flavonoid with
      formula C22H28O14. CONCLUSIONS: F. sycomorus reversed the harmful effects of UCMS
      on mood and behaviors in rats and it possesses an antidepressant property that is
      at least in part mediated through the oxidative pathway.

PMID- 29179736
TI  - Phylogenetic analysis of the core histone doublet and DNA topo II genes of
      Marseilleviridae: evidence of proto-eukaryotic provenance.
AB  - BACKGROUND: While the genomes of eukaryotes and Archaea both encode the histone
      fold domain, only eukaryotes encode the core histone paralogs H2A, H2B, H3, and
      H4. With DNA, these core histones assemble into the nucleosomal octamer
      underlying eukaryotic chromatin. Importantly, core histones for H2A and H3 are
      maintained as neofunctionalized paralogs adapted for general bulk chromatin
      (canonical H2 and H3) or specialized chromatin (H2A.Z enriched at gene promoters
      and cenH3s enriched at centromeres). In this context, the identification of core
      histone-like "doublets" in the cytoplasmic replication factories of the
      Marseilleviridae (MV) is a novel finding with possible relevance to understanding
      the origin of eukaryotic chromatin. Here, we analyze and compare the core histone
      doublet genes from all known MV genomes as well as other MV genes relevant to the
      origin of the eukaryotic replisome. RESULTS: Using different phylogenetic
      approaches, we show that MV histone domains encode obligate H2B-H2A and H4-H3
      dimers of possible proto-eukaryotic origin. MV core histone moieties form sister
      clades to each of the four eukaryotic clades of canonical and variant core
      histones. This suggests that MV core histone moieties diverged prior to
      eukaryotic neofunctionalizations associated with paired linear chromosomes and
      variant histone octamer assembly. We also show that MV genomes encode a proto
      eukaryotic DNA topoisomerase II enzyme that forms a sister clade to eukaryotes.
      This is a relevant finding given that DNA topo II influences histone deposition
      and chromatin compaction and is the second most abundant nuclear protein after
      histones. CONCLUSIONS: The combined domain architecture and phylogenomic analyses
      presented here suggest that a primitive origin for MV histone genes is a more
      parsimonious explanation than horizontal gene transfers + gene fusions +
      sufficient divergence to eliminate relatedness to eukaryotic
      neofunctionalizations within the H2A and H3 clades without loss of relatedness to
      each of the four core histone clades. We thus suggest MV histone doublet genes
      and their DNA topo II gene possibly were acquired from an organism with a
      chromatinized replisome that diverged prior to the origin of eukaryotic core
      histone variants for H2/H2A.Z and H3/cenH3. These results also imply that core
      histones were utilized ancestrally in viral DNA compaction and/or protection from
      host endonucleases.

PMID- 29179737
TI  - Dose-dependent effect of daptomycin on the artificial prolongation of prothrombin
      time in coagulation abnormalities: in vitro verification.
AB  - BACKGROUND: Several studies have reported that daptomycin induced artificial
      prolongation of prothrombin time (PT) in some test reagents, particularly in
      warfarin users. However, it remains unknown whether the artificial prolongation
      can be affected by coagulation abnormalities other than the use of warfarin.
      Thus, we investigated the effect of daptomycin on PT with two types of
      coagulation abnormalities. METHODS: Plasma samples were pooled by four groups:
      healthy volunteers (Plasma A), warfarin users with a PT-international normalized
      ratio (INR) of approximately 2.0 (Plasma B) or 3.0 (Plasma C), and patients with
      liver cirrhosis with a PT-INR of approximately 2.0 (Plasma D). Plasma A was
      composed of plasma from two healthy individuals (9 mL from each individual).
      Plasma B, C, and D were composed of plasma from 36 patients (0.5 mL from each
      patient). Daptomycin was added to each sample to create solutions with several
      concentrations (0-150 MUg/mL). The PT-INR for each solution was measured with
      three PT reagents. Linear regression analyses were used to determine the
      association between daptomycin concentration and PT-INR. The relative change in
      PT-INR due to daptomycin concentrations was calculated. RESULTS: Strong linear
      correlations were observed between daptomycin concentrations and PT-INR for all
      the plasma groups and reagents (R2 > 0.7, P < 0.01). At a daptomycin
      concentration of 150 MUg/mL, the relative increase of PT-INR was >=10% in the
      majority of the plasma groups with an elevated baseline PT-INR in all reagents
      tested. CONCLUSIONS: Daptomycin induced the artificial prolongation of PT-INR in
      a concentration-dependent manner, particularly in plasma samples with an elevated
      baseline PT-INR. PT should be evaluated at the trough levels of daptomycin.

PMID- 29179738
TI  - Laser-modified titanium surfaces enhance the osteogenic differentiation of human
      mesenchymal stem cells.
AB  - BACKGROUND: Titanium surfaces have been modified by various approaches with the
      aim of improving the stimulation of osseointegration. Laser beam (Yb-YAG)
      treatment is a controllable and flexible approach to modifying surfaces. It
      creates a complex surface topography with micro and nano-scaled patterns, and an
      oxide layer that can improve the osseointegration of implants, increasing their
      usefulness as bone implant materials. METHODS: Laser beam irradiation at various
      fluences (132, 210, or 235 J/cm2) was used to treat commercially pure titanium
      discs to create complex surface topographies. The titanium discs were
      investigated by scanning electron microscopy, X-ray diffraction, and measurement
      of contact angles. The surface generated at a fluence of 235 J/cm2 was used in
      the biological assays. The behavior of mesenchymal stem cells from an umbilical
      cord vein was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, a mineralization assay, and an alkaline
      phosphatase activity assay and by carrying out a quantitative real-time
      polymerase chain reaction for osteogenic markers. CHO-k1 cells were also exposed
      to titanium discs in the MTT assay. RESULTS: The best titanium surface was that
      produced by laser beam irradiation at 235 J/cm2 fluence. Cell proliferation
      analysis revealed that the CHO-k1 and mesenchymal stem cells behaved differently.
      The laser-processed titanium surface increased the proliferation of CHO-k1 cells,
      reduced the proliferation of mesenchymal stem cells, upregulated the expression
      of the osteogenic markers, and enhanced alkaline phosphatase activity.
      CONCLUSIONS: The laser-treated titanium surface modulated cellular behavior
      depending on the cell type, and stimulated osteogenic differentiation. This
      evidence supports the potential use of laser-processed titanium surfaces as bone
      implant materials, and their use in regenerative medicine could promote better
      outcomes.

PMID- 29179739
TI  - Subjective cognitive impairment and brain structural networks in Chinese
      gynaecological cancer survivors compared with age-matched controls: a cross
      sectional study.
AB  - BACKGROUND: Subjective cognitive impairment can be a significant and prevalent
      problem for gynaecological cancer survivors. The aims of this study were to
      assess subjective cognitive functioning in gynaecological cancer survivors after
      primary cancer treatment, and to investigate the impact of cancer treatment on
      brain structural networks and its association with subjective cognitive
      impairment. METHODS: This was a cross-sectional survey using a self-reported
      questionnaire by the Functional Assessment of Cancer Therapy-Cognitive Function
      (FACT-Cog) to assess subjective cognitive functioning, and applying DTI
      (diffusion tensor imaging) and graph theoretical analyses to investigate brain
      structural networks after primary cancer treatment. RESULTS: A total of 158
      patients with gynaecological cancer (mean age, 45.86 years) and 130 age-matched
      non-cancer controls (mean age, 44.55 years) were assessed. Patients reported
      significantly greater subjective cognitive functioning on the FACT-Cog total
      score and two subscales of perceived cognitive impairment and perceived cognitive
      ability (all p values <0.001). Compared with patients who had received surgery
      only and non-cancer controls, patients treated with chemotherapy indicated the
      most altered global brain structural networks, especially in one of properties of
      small-worldness (p = 0.004). Reduced small-worldness was significantly associated
      with a lower FACT-Cog total score (r = 0.412, p = 0.024). Increased
      characteristic path length was also significantly associated with more subjective
      cognitive impairment (r = -0.388, p = 0.034). CONCLUSION: When compared with non
      cancer controls, a considerable proportion of gynaecological cancer survivors may
      exhibit subjective cognitive impairment. This study provides the first evidence
      of brain structural network alteration in gynaecological cancer patients at post
      treatment, and offers novel insights regarding the possible neurobiological
      mechanism of cancer-related cognitive impairment (CRCI) in gynaecological cancer
      patients. As primary cancer treatment can result in a more random organisation of
      structural brain networks, this may reduce brain functional specificity and
      segregation, and have implications for cognitive impairment. Future prospective
      and longitudinal studies are needed to build upon the study findings in order to
      assess potentially relevant clinical and psychosocial variables and brain network
      measures, so as to more accurately understand the specific risk factors related
      to subjective cognitive impairment in the gynaecological cancer population. Such
      knowledge could inform the development of appropriate treatment and
      rehabilitation efforts to ameliorate cognitive impairment in gynaecological
      cancer survivors.

PMID- 29179740
TI  - Childhood disability in Malawi: a population based assessment using the key
      informant method.
AB  - BACKGROUND: Epidemiological data on childhood disability are lacking in Low and
      Middle Income countries (LMICs) such as Malawi, hampering effective service
      planning and advocacy. The Key Informant Method (KIM) is an innovative, cost
      effective method for generating population data on the prevalence and causes of
      impairment in children. The aim of this study was to use the Key Informant Method
      to estimate the prevalence of moderate/severe, hearing, vision and physical
      impairments, intellectual impairments and epilepsy in children in two districts
      in Malawi and to estimate the associated need for rehabilitation and other
      services. METHODS: Five hundred key informants (KIs) were trained to identify
      children in their communities who may have the impairment types included in this
      study. Identified children were invited to attend a screening camp where they
      underwent assessment by medical professionals for moderate/severe hearing, vision
      and physical impairments, intellectual impairments and epilepsy. RESULTS:
      Approximately 15,000 children were identified by KIs as potentially having an
      impairment of whom 7220 (48%) attended a screening camp. The estimated prevalence
      of impairments/epilepsy was 17.3/1000 children (95% CI: 16.9-17.7). Physical
      impairment (39%) was the commonest impairment type followed by hearing impairment
      (27%), intellectual impairment (26%), epilepsy (22%) and vision impairment (4%).
      Approximately 2100 children per million population could benefit from
      physiotherapy and occupational therapy and 300 per million are in need of a
      wheelchair. An estimated 1800 children per million population have hearing
      impairment caused by conditions that could be prevented or treated through basic
      primary ear care. Corneal opacity was the leading cause of vision impairment.
      Only 50% of children with suspected epilepsy were receiving medication. The
      majority (73%) of children were attending school, but attendance varied by
      impairment type and was lowest among children with multiple impairments (38%).
      CONCLUSION: Using the KIM this study identified more than 2500 children with
      impairments in two districts of Malawi. As well as providing data on child
      disability, rehabilitation and referral service needs which can be used to plan
      and advocate for appropriate services and interventions, this method study also
      has an important capacity building and disability awareness raising component.

PMID- 29179741
TI  - Dietary energy drives the dynamic response of bovine rumen viral communities.
AB  - BACKGROUND: Rumen microbes play a greater role in host energy acquisition than
      that of gut-associated microbes in monogastric animals. Although genome-enabled
      advancements are providing access to the vast diversity of uncultivated microbes,
      our understanding of variables shaping rumen microbial communities is in its
      infancy. Viruses have been shown to impact microbial populations through a myriad
      of processes, including cell lysis and reprogramming of host metabolism. However,
      little is known about the processes shaping the distribution of rumen viruses or
      how viruses may modulate microbial-driven processes in the rumen. To this end, we
      investigated how rumen bacterial and viral community structure and function
      responded in five steers fed four randomized dietary treatments in a crossover
      design. RESULTS: Total digestible nutrients (TDN), a measure of dietary energy,
      best explained the variation in bacterial and viral communities. Additional
      ecological drivers of viral communities included dietary zinc content and
      microbial functional diversity. Using partial least squares regression, we
      demonstrate significant associations between the abundances of 267 viral
      populations and variables driving the variation in rumen viral communities. While
      rumen viruses were dynamic, 14 near ubiquitous viral populations were identified,
      suggesting the presence of a core rumen virome largely comprised of novel
      viruses. Moreover, analysis of virally encoded auxiliary metabolic genes (AMGs)
      indicates rumen viruses have glycosidic hydrolases to potentially augment the
      breakdown of complex carbohydrates to increase energy production. Other AMGs
      identified have a role in redirecting carbon to the pentose phosphate pathway and
      one carbon pools by folate to boost viral replication. CONCLUSIONS: We
      demonstrate that rumen bacteria and viruses have differing responses and
      ecological drivers to dietary perturbation. Our results show that rumen viruses
      have implications for understanding the structuring of the previously identified
      core rumen microbiota and impacting microbial metabolism through a vast array of
      AMGs. AMGs in the rumen appear to have consequences for microbial metabolism that
      are largely in congruence with the current paradigm established in marine
      systems. This study provides a foundation for future hypotheses regarding the
      dynamics of viral-mediated processes in the rumen.

PMID- 29179742
TI  - Neuroimaging genomics in psychiatry-a translational approach.
AB  - Neuroimaging genomics is a relatively new field focused on integrating genomic
      and imaging data in order to investigate the mechanisms underlying brain
      phenotypes and neuropsychiatric disorders. While early work in neuroimaging
      genomics focused on mapping the associations of candidate gene variants with
      neuroimaging measures in small cohorts, the lack of reproducible results inspired
      better-powered and unbiased large-scale approaches. Notably, genome-wide
      association studies (GWAS) of brain imaging in thousands of individuals around
      the world have led to a range of promising findings. Extensions of such
      approaches are now addressing epigenetics, gene-gene epistasis, and gene
      environment interactions, not only in brain structure, but also in brain
      function. Complementary developments in systems biology might facilitate the
      translation of findings from basic neuroscience and neuroimaging genomics to
      clinical practice. Here, we review recent approaches in neuroimaging genomics-we
      highlight the latest discoveries, discuss advantages and limitations of current
      approaches, and consider directions by which the field can move forward to shed
      light on brain disorders.

PMID- 29179743
TI  - Visceral and subcutaneous abdominal adiposity and pulmonary function in 30-year
      old adults: a cross-sectional analysis nested in a birth cohort.
AB  - BACKGROUND: Several studies have verified body fat distribution in association
      with pulmonary function (PF), mainly waist circumference, but few have used
      measures able to distinguish abdominal fat compartments. The present study aims
      to verify the association of visceral adipose tissue (VAT) and subcutaneous
      adipose tissue (SAT) with PF measures. METHODS: In 1982, all hospital births
      occurring in Pelotas, Brazil, were identified and those livebirths have been
      followed. In 2012-13, the cohort participants were evaluated and VAT and SAT
      measured using ultrasound; forced expiratory volume in the first second (FEV1) or
      forced vital capacity (FVC) were patronized in z-scores stratified by sex. The
      associations were verified using crude and adjusted linear regressions. RESULTS:
      The present analyses comprised 3438 individuals (1721 women). VAT was inversely
      associated with spirometric parameters, in both crude and adjusted models. SAT
      showed inverse associations in the crude analyzes in males and a positive trend
      after adjustment, except for SAT and FVC in males. To each centimeter of VAT,
      mean adjusted FEV1 z-scores decreased 0.072 (95% CI -0.107; -0.036) in men and
      0.127 (95% CI -0.164; -0.090) in women, and FVC z-scores decreased -0.075 (95% CI
      -0.111; -0.039) and 0.121 (95% CI -0.158; -0.083), in men and women,
      respectively. CONCLUSIONS: VAT has a consistent inverse association with FEV1 and
      FVC in both sexes. On the other hand, SAT showed inconsistent results with PF
      parameters.

PMID- 29179745
TI  - Reproducibility of the 75 g oral glucose tolerance test for the diagnosis of
      gestational diabetes mellitus in a sub-Saharan African population.
AB  - OBJECTIVE: To evaluate the reproducibility of the 75 g oral glucose tolerance
      test and factors associated with non-reproducible results in Cameroonian pregnant
      women. RESULTS: Twenty-seven of the 84 participants (32.1%) who did the first
      oral glucose tolerance test were diagnosed with gestational diabetes mellitus.
      There was no difference between the means of the glycaemic responses at T0 (p =
      0.64), T30 (p = 0.08), T60 (p = 0.86), T90 (p = 0.51), and T120 (p = 0.34)
      between the two oral glucose tolerance test. Age (p = 0.001) and BMI (p = 0.001)
      were significantly associated with non-reproducible results. The reproducibility
      of the oral glucose tolerance test in this study was 74.2%, and the kappa
      statistic's 0.46. In conclusion, the results of the oral glucose tolerance test
      were reproducible in only 74.2% of pregnant women in this study. This highlights
      that a single oral glucose tolerance test for the diagnosis of gestational
      diabetes mellitus should be interpreted with caution.

PMID- 29179744
TI  - Levels, trends and correlates of unmet need for family planning among postpartum
      women in Indonesia: 2007-2015.
AB  - BACKGROUND: Although Indonesia has relatively high contraceptive prevalence,
      postpartum family planning (PP-FP) has not been a particular point of emphasis.
      This article reports the results of analyses undertaken in order to (1) better
      understand levels and trends in unmet need for family planning among postpartum
      women, (2) assess the extent to which unmet need is concentrated among particular
      population sub-groups, and (3) assess the policy priority that PP-FP should have
      in relation to other interventions. METHODS: The analyses were based on data from
      the 2007 and 2012 Indonesia Demographic and Health Surveys (IDHS) and the 2015
      PMA2020 survey. Postpartum contraceptive use and unmet need were analyzed for
      fecund women who had given birth in the 3-5 years of preceding the respective
      surveys who were in the extended postpartum period at the time of the respective
      surveys. Factors associated with contraceptive use and unmet were assessed via
      multivariable logistic regressions using merged data from all three surveys. A
      wide range of biologic, demographic, socio-economic, geographic and programmatic
      factors were considered. RESULTS: Contraceptive use during the extended
      postpartum period is high in Indonesia, with more than 74% of post-partum women
      reporting currently using a family planning method in the 2015 PMA2020 survey.
      This is up from 68% in 2007 and 70% in 2012. Total unmet need was 28% in 2007,
      falling slightly to 23% in 2012 and 24% in 2015. However, the timing of
      contraceptive initiation is less than optimal. By six months postpartum, only 50%
      of mothers had begun contraceptive use. Unmet need was highest among older women,
      women with 4+ children, with limited knowledge of contraceptive methods, making
      fewer ANC visits, from poor families and residents of islands other than Java and
      Bali. CONCLUSION: Unmet need for family planning among postpartum women in
      Indonesia is low in comparison with other low- and middle-income countries.
      However, because of limited durations of exclusive breastfeeding, many Indonesian
      women do not initiate contraception early enough after delivering children. Given
      already high contraceptive prevalence, targeting postpartum women for increased
      programmatic attention would seem strategically prudent.

PMID- 29179746
TI  - Association of Interleukin-1 gene clusters polymorphisms with primary open-angle
      glaucoma: a meta-analysis.
AB  - BACKGROUND: Previous studies have associated the Interleukin-1 (IL-1) gene
      clusters polymorphisms with the risk of primary open-angle glaucoma (POAG).
      However, the results were not consistent. Here, we performed a meta-analysis to
      evaluate the role of IL-1 gene clusters polymorphisms in POAG susceptibility.
      METHODS: PubMed, EMBASE and Cochrane Library (up to July 15, 2017) were searched
      by two independent investigators. All case-control studies investigating the
      association between single-nucleotide polymorphisms (SNPs) of IL-1 gene clusters
      and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals
      (CIs) were calculated for quantifying the strength of association that has been
      involved in at least two studies. RESULTS: Five studies on IL-1beta rs16944 (c. 
      511C > T) (1053 cases and 986 controls), 4 studies on IL-1alpha rs1800587 (c. 
      889C > T) (822 cases and 714 controls), and 4 studies on IL-1beta rs1143634 (c.
      +3953C > T) (798 cases and 730 controls) were included. The results suggest that
      all three SNPs were not associated with POAG risk. Stratification analyses
      indicated that the rs1143634 has a suggestive associated with high tension
      glaucoma (HTG) under dominant (P = 0.03), heterozygote (P = 0.04) and allelic
      models (P = 0.02), however, the weak association was nullified after Bonferroni
      adjustments for multiple tests. CONCLUSIONS: Based on current meta-analysis, we
      indicated that there is lack of association between the three SNPs of IL-1 and
      POAG. However, this conclusion should be interpreted with caution and further
      well designed studies with large sample-size are required to validate the
      conclusion as low statistical powers.

PMID- 29179747
TI  - Optimal reduction of chemical oxygen demand and NH3-N from landfill leachate
      using a strongly resistant novel Bacillus salmalaya strain.
AB  - BACKGROUND: When the unavoidable waste generation is considered as damaging to
      our environment, it becomes crucial to develop a sustainable technology to
      remediate the pollutant source towards an environmental protection and safety.
      The development of a bioengineering technology for highly efficient pollutant
      removal is this regard. Given the high ammonia nitrogen content and chemical
      oxygen demand of landfill leachate, Bacillus salmalaya strain 139SI, a novel
      resident strain microbe that can survive in high ammonia nitrogen concentrations,
      was investigated for the bioremoval of ammonia nitrogen from landfill leachate.
      The treatability of landfill leachate was evaluated under different treatment
      parameters, such as temperature, inoculum dosage, and pH. RESULTS: Results
      demonstrated that bioaugmentation with the novel strain can potentially improve
      the biodegradability of landfill leachate. B. salmalaya strain 139SI showed high
      potential to enhance biological treatment given its maximum NH3-N and COD removal
      efficiencies. The response surface plot pattern indicated that within 11 days and
      under optimum conditions (10% v/v inoculant, pH 6, and 35  degrees C), B.
      salmalaya strain139SI removed 78% of ammonia nitrogen. At the end of the study,
      biological and chemical oxygen demands remarkably decreased by 88% and 91.4%,
      respectively. Scanning electron microscopy images revealed that ammonia ions
      covered the cell surface of B. salmalaya strain139SI. CONCLUSIONS: Therefore,
      novel resistant Bacillus salmalaya strain139SI significantly reduces the chemical
      oxygen demand and NH3-N content of landfill leachate. Leachate treatment by B.
      salmalaya strain 139SI within 11 days.

PMID- 29179748
TI  - Quantifying bone marrow inflammatory edema in the spine and sacroiliac joints
      with thresholding.
AB  - BACKGROUND: Psoriatic Arthritis (PsA) is a chronic inflammatory arthritis that
      develops in patients with psoriasis. Inflammatory edema in the spine may reflect
      subclinical disease activity and be a predictor of radiographic progression. A
      semi-quantitative method established by the spondyloarthritis research consortium
      of Canada (SPARCC) is commonly used to assess the disease activity in MR images
      of the spine. This study aims to evaluate thresholding for quantification of
      subtle bone marrow inflammation in the spine and the sacroiliac (SI) joints of
      patients with PsA and compare it with the SPARCC scoring system. METHODS: Short
      tau inversion recovery (STIR) MR images of the spine (N = 85) and the SI joints
      (N = 95) of patients with PsA (N = 41) were analyzed. A threshold was applied to
      visible bone marrow in order to mask areas with higher signal intensity, which
      are consistent with inflammation. These areas were considered as inflammatory
      lesions. The volume and relative signal intensity of the lesions were calculated.
      Results from thresholding were compared to SPARCC scores using linear mixed
      effects models. The specificity and sensitivity of thresholding were also
      calculated. RESULTS: A significant positive correlation between the volumes and
      mean relative signal intensities, which were calculated by thresholding analysis,
      and the SPARCC scores was detected for both spine (p < 0.001) and SI joints (p <
      0.001). For the spine, thresholding had sensitivity and specificity of 83% and
      76% respectively, while for the SI joints the values were 51% and 88%
      respectively. CONCLUSIONS: Thresholding allows quantification of subtle bone
      marrow inflammatory edema in patients with psoriatic arthritis, and could support
      SPARCC scoring of the spine. Improved image processing and inclusion of automatic
      segmentation are required for thresholding of STIR images to become a rapid and
      reliable method for quantitative measures of inflammation. TRIAL REGISTRATION:
      NCT02995460 (December 14, 2016) - Retrospectively registered.

PMID- 29179749
TI  - Evaluation of the three-in-one team-based care model on hierarchical diagnosis
      and treatment patterns among patients with diabetes: a retrospective cohort study
      using Xiamen's regional electronic health records.
AB  - BACKGROUND: Xiamen is a pilot city in China for hierarchical diagnosis and
      treatment reform of non-communicable diseases, especially diabetes. Since 2012,
      Xiamen has implemented a program called the "three-in-one", a team-based care
      model for the treatment of diabetes, which involves collaboration between
      diabetes specialists, general practitioners, and health managers. In addition,
      the program provides financial incentives to improve care, as greater
      accessibility to medications through community health care centers (CHCs). The
      aim of this study was to evaluate the effectiveness of these policies in shifting
      visits from general hospitals to CHCs for the treatment of type 2 diabetes
      mellitus (T2DM). METHOD AND MATERIALS: A retrospective observational cohort study
      was conducted using Xiamen's regional electronic health record (EHR) database,
      which included 90% of all patients registered since 2012. Logistic regression was
      used to derive the adjusted odds ratio (OR) for patients shifting from general
      hospitals to CHCs. Among patients treated at hospitals, Kaplan-Meier(KM) curves
      were constructed to evaluate the time from each policy introduction until the
      switch to CHCs. A k-means clustering analysis was conducted to identify patterns
      of patient care-seeking behavior. RESULTS: In total, 89,558 patients and
      2,373,524 visits were included. In contrast to increased outpatient visits to
      general hospitals in China overall, the percentage of visits to CHCs in Xiamen
      increased from 29.7% in 2012 to 66.5% in 2016. The most significant and rapid
      shift occurred in later periods after full policy implementation. Three clusters
      of patients were identified with different levels of complications and health
      care-seeking frequency. All had similar responses to the policies. CONCLUSIONS:
      The "three-in-one" team-based care model showed promising results for building a
      hierarchical health care system in China. These policy reforms effectively
      increased CHCs utilization among diabetic patients.

PMID- 29179750
TI  - Safety evaluation of the interchangeable use of robenacoxib (OnsiorTM) tablets
      and solution for injection in dogs.
AB  - BACKGROUND: Robenacoxib (OnsiorTM) is a non-steroidal anti-inflammatory drug
      developed for canine and feline use for the control of pain and inflammation. It
      is available as both tablets and solution for injection. The objective of this
      safety study was to investigate the interchangeable use of two robenacoxib
      formulations in dogs using a novel study design alternating between oral tablets
      and subcutaneous injections. Thirty-two naive healthy 4-month dogs were enrolled
      in this 88-day study and were randomized among four groups to be untreated or to
      receive robenacoxib at the highest recommended or elevated dose rates. The dogs
      were administered three 20-day treatment cycles each separated by a 14-day
      washout period. Each 20-day cycle was comprised of 10 days of once daily oral
      administration, 3 days of subcutaneous administration, followed by further 7 days
      of oral administration (Groups 2 to 4). The control group (Group 1) received oral
      empty gelatin capsules or subcutaneous saline injections. Assessment of safety
      was based on general health observations, clinical observations, physical and
      neurological examinations including ophthalmological examinations,
      electrocardiographic examinations and clinical pathology evaluations, food and
      water consumption, body weight, and macroscopic and microscopic examinations.
      Blood samples were collected for pharmacokinetic evaluation. RESULTS: Blood
      concentrations of robenacoxib confirmed systemic exposure of all treated dogs.
      All dogs were in good health through study termination and there were no serious
      adverse events during the course of the study. No changes in body weight, food
      consumption, ophthalmic, neurological examinations, electrocardiograms, buccal
      mucosal blood times, clinical pathology or organ weight were attributable to
      robenacoxib formulation administration. Primary treatment-related abnormalities
      were of low incidence at all doses. They were confined to macroscopic and
      microscopic changes observed locally at the subcutaneous injection sites and
      microscopic findings within the gastrointestinal tract. These findings were as
      expected based on previous studies with robenacoxib solution for injection alone
      and the known properties of this class of compound and mode of administration.
      There were no adverse effects which could be attributed specifically to the
      interchangeable use of oral and injectable robenacoxib. CONCLUSIONS: Alternating
      regimens of robenacoxib tablets and solution for injection were well tolerated in
      healthy young dogs.

PMID- 29179751
TI  - Prospective phase-II-study evaluating postoperative radiotherapy of cervical and
      endometrial cancer patients using protons - the APROVE-trial.
AB  - BACKGROUND: The prognosis for patients with cervical or endometrial cancer has
      improved over the last decades. Thus, reducing therapy-related toxicity and
      impact on quality of life have become more and more important. With the
      development of new radiotherapy techniques like IMRT (Intensity-modulated
      radiotherapy) the incidence of acute and chronic toxicities has already been
      reduced. Nevertheless, rates of complications requiring medical treatment range
      from 0.7-8% according to literature. 7.7% of patients develop severe
      complications after 5 years with an increasing risk for complications of
      0.3%/year. Particularly, the volume of the small and large bowel receiving low
      doses (15 Gy) has been shown to be a predictive factor for the development of
      higher bowel toxicity. With the introduction of proton therapy into clinical
      practice, there are new opportunities for optimization of organ at risk-sparing
      thus possibly reducing toxicity. METHODS/DESIGN: The APROVE study is a
      prospective single-center one-arm phase-II-study. Patients with cervical or
      endometrial cancer after surgical resection who have an indication for
      postoperative pelvic radiotherapy will be treated with proton therapy instead of
      the commonly used photon radiation. A total of 25 patients will be included in
      this trial. Patients will receive a dose of 45-50.4 GyE in 1.8 GyE fractions 5-6
      times per week using active raster-scanning pencil beam proton radiation.
      Platinum-based chemotherapy can be administered if indicated. For treatment
      planning, rectum, sigma, large and small bowel, bladder and femoral heads are
      defined as organs at risk. The CTV is defined according to the RTOG consensus
      guidelines. DISCUSSION: The primary endpoint of the study is the evaluation of
      safety and treatment tolerability of pelvic radiation using protons defined as
      the lack of any CTC AE Grade 3 or 4 toxicity. Secondary endpoints are clinical
      symptoms and toxicity, quality of life and progression-free survival. The aim is
      to explore the potential of proton therapy as a new method for adjuvant pelvic
      radiotherapy to decrease the dose to the bowel, rectum and bladder thus reducing
      acute and chronic toxicity and improving quality of life. TRIAL REGISTRATION:
      Registered at https://clinicaltrials.gov , ClinicalTrials.gov Identifier:
      NCT03184350 , registered 09 June 2017, enrolment of the first participant 19 June
      2017.

PMID- 29179752
TI  - Characteristics and determinants of clinical symptoms in radiographic lumbar
      spinal stenosis in a tertiary health care centre in sub-Saharan Africa.
AB  - BACKGROUND: Lumbar spinal stenosis (LSS) refers to narrowing of the lumbar
      central spinal canal, lateral recess, and/or neuro-foramina. Radiographic LSS
      plays an important role in clinical LSS but is not solely accountable for the
      presence of symptoms. We sought to characterise clinical LSS and to determine
      factors associated with presence of symptoms of LSS in patients with radiographic
      LSS in a sub Saharan Africa setting. METHODS: After prior ethical clearance, a
      case control study was done in a tertiary hospital in Douala-Cameroon, including
      105 patients with radiographic LSS: 57 with symptoms of LSS (cases) and 58 with
      no symptoms (controls). Spinal stenosis was assessed using computed tomography
      (CT) scans. Data were analysed using SPSS version 23. RESULTS: The mean age of
      our study participants was 53.4 +/- 13.1 years. The mean age of onset of symptoms
      of LSS was 50.3 +/- 11.6 years and the most common symptoms were Low back pain
      (100.0%), radicular symptoms (98.2%) and neurogenic claudication (98.2%). Obesity
      (p < 0.001) and a high waist circumference (p = 0.002) were significantly
      associated with presence of LSS symptoms in persons with radiographic LSS. After
      adjusting for body mass index, a positive family history of low back pain (p =
      0.004), vertebra lesion at L2 (p = 0.034), L3 (p = 0.002), L4 (p = 0.025) and
      multiple (p = 0.008) levels, degenerative disc protrusion (p = 0.044), disc
      lesion at L3-L4 (p = 0.001), L4-L5 (p = 0.011) and multiple (p = 0.046) levels
      were significantly associated with presence of symptoms of LSS in persons with
      radiographic LSS. CONCLUSION: Characteristics of clinical LSS have been described
      in this sub-Saharan Africa population. Obesity, a high waist circumference and a
      positive family history of low back pain are significantly associated with
      presence of symptoms of LSS in persons with radiographic LSS.

PMID- 29179753
TI  - Development and psychometric properties of a questionnaire to measure drug users'
      attitudes toward methadone maintenance treatment (DUAMMT) in Iran.
AB  - BACKGROUND: Assessing drug users' attitudes towards different kinds of addiction
      treatment is necessary to design tailored strategies. The aim of the present
      study is to develop and examine the psychometric properties of a new scale,
      called the DUAMMT, for assessing drug users' attitudes toward methadone
      maintenance treatment in Iran. METHODS: A multi-phase development method was
      applied in developing an instrument from February to December 2016. The item
      generation and scale development were performed through literature review, a
      qualitative approach, and interviews with an expert panel. Then, the psychometric
      properties of the scale were evaluated by means of cross-sectional studies with
      drug users. We performed an exploratory factor analysis, a confirmatory factor
      analysis, and item-scale correlations; and we tested the internal consistency of
      the scale. Furthermore, test-retest reliability was evaluated among an Iranian
      sample of drug users. RESULTS: The mean age of participants was 34.12 years. The
      exploratory factor analysis revealed four factors (perceived barriers, perceived
      concerns, methadone side effects, and perceived positive effects) containing 17
      items that jointly accounted for 60.53% of the observed variance. The
      confirmatory factor analysis showed a model with appropriate fitness for the
      data. The Cronbach's alpha coefficient for the subscales ranged from .70 to .79.
      The intra-class correlation coefficient (ICC) ranged from .774 to .970, which is
      well above the acceptable threshold. CONCLUSIONS: The findings of the present
      study suggest that the DUAMMT is a valid and reliable instrument to measure drug
      users' attitudes toward methadone maintenance treatment. The DUAMMT can be
      applied at the start of treatment so that clinical intervention can be targeted
      to promote retention in treatment.

PMID- 29179754
TI  - Quantitative evaluation of subchondral bone microarchitecture in knee
      osteoarthritis using 3T MRI.
AB  - BACKGROUND: Osteoarthritis (OA) is now increasingly recognized as being related
      to the whole joint instead of the cartilage alone. In particular, the importance
      of subchondral bone in OA pathogenesis has drawn a lot of interest. The aim of
      this study is to investigate subchondral bone microstructural features in two
      femoral condyles of human knee osteoarthritis. METHODS: Eighty subjects were
      enrolled in our study and divided into three groups: without OA (group 0), mild
      OA (group 1), and severe OA (group 2). Sagittal 3D Balanced Fast Field Echo (3D
      FFE) images were obtained by 3T MRI to quantify trabecular bone structure, and
      sagittal FatSat 3D Fast Field Echo (3D-FFE) images were acquired to assess
      cartilage thickness. Trabecular bone parameters, including bone volume fraction
      (BVF), erosion index (EI) and the trabecular plate-to-rod ratio (SCR), and
      trabecular thickness were evaluated using digital topological analysis.
      Subchondral bone and cartilage parameters between different groups and different
      locations were compared, and their correlations were analyzed. RESULTS: Within
      two femoral condyles, subchondral bone structure was deteriorated in mild OA,
      showing a lower BVF (-0.011 to -0.014 P < 0.001), a higher EI (0.346 to 0.310 P <
      0.001), a lower SCR (-0.581 to -0.542 P < 0.001)) and lower trabecular thickness
      (-6.588 to -4.759 P < 0.05). In severe OA, BVF was further decreased, but EI, SCR
      and trabecular thickness showed no significant difference than mild OA(P > 0.05).
      Moreover, there was a lower BVF, SCR and higher EI in the medial femoral condyle
      in each group. Interestingly, cartilage attrition mainly occurred in the medial
      femoral condyle. Medial cartilage thickness was not only positively correlated
      with the ipsilateral femoral BVF (r = 0.321 P = 0.004) but also with the opposite
      femoral BVF (r = 0.270 P = 0.015). CONCLUSIONS: Our results indicated that
      deterioration in the trabecular bone structure in both femoral condyles could
      more sensitively reveal early OA, and BVF could be a better biomarker to evaluate
      OA severity.

PMID- 29179755
TI  - Fever after bronchoscopy: serum procalcitonin enables early diagnosis of post
      interventional bacterial infection.
AB  - BACKGROUND: The aim of this study was to differentiate unspecific and self
      limiting fever after bronchoscopy from fever due to infection by using serum
      procalcitonin, C-reactive protein and neutrophil count. Furthermore, frequency of
      fever after bronchoscopy and procedures as possible risk factors were evaluated.
      METHODS: Three hundred and fourteen consecutive patients were included. All
      bronchoscopies were performed using jet-ventilation and general anesthesia.
      Patients were analyzed according to interventions performed during bronchoscopy
      and laboratory results. Microbiological assessment was done in patients who
      developed fever to prove or rule out a bacterial infection. RESULTS: Forty-four
      patients showed fever within 24 h following bronchoscopy (14%). A bacterial
      infection was proven in 11 patients with fever (3.5%). Procalcitonin, neutrophil
      count and C-reactive protein were significantly higher in patients with fever
      after bronchoscopy compared to non-fever patients. To predict bacterial infection
      in the receiver operating analysis, procalcitonin had the highest area under the
      curve (0.942; 95% confidence interval [CI], 0.768 to 1.000; p = <0.001), followed
      by neutrophil count (AUC, 0.804; 95% CI, 0.606 to 0.946; p = 0.005), whereas CRP
      levels where not statistically significant. Endoscopic airway recanalization was
      the only intervention that induced fever more frequently than all other
      interventions (OR 13.629). CONCLUSIONS: Fever is frequently seen after
      bronchoscopy and in some cases caused by bacterial infection. Procalcitonin might
      be useful to distinguish a bacterial infection from unspecific self-limiting
      fever. Airway recanalization is a procedure that seems to induce fever
      significantly more often than other bronchoscopic interventions.

PMID- 29179756
TI  - Causes and Three-year Incidence of Irreversible Visual Impairment in Jing-An
      District, Shanghai, China from 2010-2015.
AB  - BACKGROUND: The registry system can be used to observe the distribution trend of
      diseases and analyze the related data to provide useful information in a way that
      enables the government to take appropriate interventional measures. The purpose
      of this study was to determine the causes and three-year incidence of newly
      registered disabled patients who were blind or had low vision in Jing-An
      District, Shanghai, China from 2010 to 2015. METHODS: Data from the registration
      system of visual disability in Jing-An District, Shanghai from 2010 to 2015 were
      collected and analyzed. In this registry, the only person with permanent visual
      impairment (VI) was identified as being a certified visually impaired person. The
      main causes of visual disability were obtained, the three-year incidence of
      visual disability was calculated, and the relationships between blindness or low
      vision and age, as well as those between blindness or low vision and gender, were
      analyzed. RESULTS: Six-hundred and forty-six newly certified people with VI were
      registered, including 206 blind patients and 440 low vision patients. The major
      causes of blindness were myopia macular degeneration (MMD, 23.30%), glaucoma
      (20.39%), and age-related macular degeneration (AMD, 17.96%). The three leading
      causes of low vision were MMD (58.86%), AMD (16.36%), and diabetic retinopathy
      (DR, 7.27%). DR (16.0%) was the first leading cause of blindness and the second
      leading cause of VI in patients aged 30-59 yrs. from 2010 to 2015. The three-year
      incidences of blindness in 2010-2012 and 2013-2015(P = 0.43), which remained
      stable throughout this time period, were 32.74/100000 and 36.51/100000,
      respectively. However, the three-year incidence of low vision was 64.51/100000 in
      2010-2012 and 83.58/100000 in 2013-2015(P = 0.007), which shows that the
      incidence increased significantly due to the increase of patients with low vision
      caused by MMD and DR (P = 0.003 and P = 0.01, respectively). CONCLUSIONS: MMD,
      glaucoma, and AMD were the main causes of blindness, while DR was becoming a
      major cause of VI, especially in working-age people of Jing-An District,
      Shanghai, China.

PMID- 29179757
TI  - Lockjaw from a metastatic uterine leiomyosarcoma- case report and review of the
      literature.
AB  - BACKGROUND: Leiomyosarcoma (LMS) is a malignant tumour formed of cells with
      distinct smooth muscle features. Leiomyosarcomas rarely metastasise to the oral
      cavity and this literature review details all reported cases of metastasis to the
      mandible found in the literature. This offers a unique perspective by specifying
      mandible as the site of metastasis of leiomyosarcoma. CASE PRESENTATION: A 53
      year-old female presented to her General Practitioner (GP) with heavy menstrual
      bleeding and was diagnosed with multiple fibroids. Folowing a hysterectomy and
      removal of both tubes and ovaries for these symptomatic uterine fibroids, an
      incidental diagnosis of low grade leiomyosarcoma was made. A CT scan found no
      evidence of residual or metastatic disease and no further treatment was deemed
      necessary. 6 months later she presented to A & E with a numb lower lip but it
      took another 6 months for the diagnosis of metastatic LMS to the mandible to be
      made. DISCUSSION: Leiomyosarcomas are aggressive tumours which are liable to
      metastasise and therefore have a poor prognosis. An extensive literature review
      was undertaken to explore the frequency of metastasis in the maxillo-facial
      region. CONCLUSIONS: Although metastasis to the oral region is very rare as
      suggested from the literature review, when patients present with unusual symptoms
      after a diagnosis of LMS, physicians should be aware of the possibility of LMS
      metastases.

PMID- 29179758
TI  - Developmental performance of hospitalized severely acutely malnourished under-six
      children in low- income setting.
AB  - BACKGROUND: Retrospective studies show that severe acute malnutrition (SAM)
      affects child development. However, to what extent SAM affects children of
      different ages at its acute stage is not well documented. This study was aimed at
      comparing the developmental performance of severely acutely malnourished children
      under six with that of age and gender-matched non-malnourished healthy children.
      METHODS: The developmental performances of 310 children with SAM (male = 155,
      female = 155); mean age = 30.7 mo; SD = 15.2 mo) admitted to the nutritional
      rehabilitation unit (NRU) at Jimma University's Hospital was compared with that
      of 310 age and gender-matched, non-malnourished healthy children (male = 155,
      female = 155; mean age = 29.6 mo; SD = 15.4 mo) living in Jimma Town in Ethiopia.
      Two culturally adapted tools were used: (1) the Denver II-Jimma, to assess the
      children's performance on personal social (PS), fine motor (FM) language (LA),
      gross motor (GM) skills, and (2) the Ages and Stages Questionnaires: Social
      Emotional (ASQ:SE), to assess social-emotional (SE) skills. Multivariable Poisson
      regression analysis was conducted to compare the developmental performance scores
      of SAM and non-malnourished children. RESULTS: For one-year-old children, SAM
      delays their developmental performance on GM, FM, PS and LA by 300%, 200%, 140%
      and 71.4% respectively. For three-years-old children, SAM delays their
      developmental performance on GM by 80%, on FM and LA by 50% each, and on PS by
      28.6%. Of the skills assessed on Denver II-Jimma, GM is the most, and PS is the
      least affected. Younger SAM children are more affected than older ones on all the
      domains of development. The delay in FM, GM, LA and PS generally decreases with
      an increase in age. Social-emotional behavior problems seem to be most pronounced
      in the very young and older age ranges. CONCLUSIONS: SAM has a differential age
      effect on the different dimensions of development in children under 6 years of
      age.

PMID- 29179759
TI  - Metabolic syndrome, diabetes and inadequate lifestyle in first-degree relatives
      of acute myocardial infarction survivors younger than 45 years old.
AB  - BACKGROUND: A premature myocardial infarction (PMI) is usually associated with a
      familial component. This study evaluated cardiovascular risk factors in first
      degree relatives (FDR) of patients with PMI not presenting the familial
      hypercholesterolemia phenotype. METHODS: A cross-sectional study comprising FDR
      of non-familial hypercholesterolemia patients who suffered a myocardial
      infarction <45-years age matched for age and sex with individuals without family
      history of cardiovascular disease. Subjects were evaluated for presence of the
      metabolic syndrome and its components, lifestyle, statin therapy, and laboratory
      parameters. RESULTS: The sample was composed of 166 FDR of 103 PMI patients and
      111 controls. The prevalence of smoking (29.5 vs. 6.3%; p < 0.001), prediabetes
      (40.4 vs. 27%; p < 0.001), diabetes (19.9 vs. 1.8%; p < 0.001), metabolic
      syndrome (64.7 vs. 36%; p < 0.001), and dyslipidemia (84.2 vs. 31.2%; p = 0.001)
      was greater in FDR. There was no difference on the prevalence of abdominal
      obesity between groups. In addition, FDR presented higher triglycerides (179.0 +/
      71.0 vs. 140.0 +/- 74.0 mg/dL; p = 0.002), LDL-cholesterol (122.0 +/- 36.0 vs.
      113.0 +/- 35 mg/dL; p = 0.031), non-HDL-cholesterol (157.0 +/- 53.0 vs. 141.0 +/-
      41.0 mg/dL; p = 0.004), and lower HDL-cholesterol (39.0 +/- 10.0 vs. 48.0 +/-
      14.0 mg/dL; p < 0.001) than controls. Thyrotropin levels (2.4 +/- 1.6 vs. 1.9 +/-
      1.0 mUI/L; p = 0.002) were higher in FDR. The risk factor pattern was like the
      one of index cases. Only 5.9% (n = 10) of FDR were in use of statins.
      CONCLUSIONS: FDR of non-familial hypercholesterolemia patients with PMI presented
      an elevated prevalence of metabolic abnormalities, inadequate lifestyle and were
      undertreated for dyslipidemia.

PMID- 29179760
TI  - Exploring differences in stakeholders' perceptions of illegal bird trapping in
      Cyprus.
AB  - BACKGROUND: Cyprus is recognised as a hotspot for illegal bird trapping in the
      Mediterranean basin. A consumer demand for the Eurasian blackcap (Sylvia
      atricapilla) is driving the use of non-selective trapping methods, resulting in
      the indiscriminate killing of millions of migratory birds. Efforts to tackle the
      issue have so far been characterised mostly by a top-down approach, focusing on
      legislation and enforcement. However, trapping levels are not decreasing and
      conflict between stakeholder groups is intensifying. METHODS: To understand why
      efforts to stop illegal bird trapping have not been effective, we used semi
      structured interviews to interview 18 local bird trappers and nine
      representatives from the pertinent environmental non-governmental organisations
      (NGOs) and the governmental agencies responsible for enforcing the legislation.
      RESULTS: We found distinct differences between the views of the local trapping
      community and the environmental NGOs, particularly on why trapping is occurring
      and its impact on the avifauna. This disparity has contributed to
      misrepresentations of both sides and a high degree of conflict, which is
      potentially proving counterproductive to conservation interventions. In addition,
      it appears that trappers are a heterogeneous group, likely driven by various
      motivations besides profit. CONCLUSION: We argue that stakeholders interested in
      reducing illegal bird trapping need to develop anti-poaching strategies that aim
      at minimising the disparity in the views, and subsequently the conflict,
      acknowledging also that trappers are not a homogenous group, as often treated.

PMID- 29179761
TI  - Efficacy and safety of the "Xingnao Kaiqiao" acupuncture technique via
      intradermal needling to treat postoperative gastrointestinal dysfunction of
      laparoscopic surgery: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Xingnao Kaiqiao acupuncture involves needling of the Neiguan (PC6),
      Renzhong (DU26), and Sanyinjiao (SP6) acupoints. The technique has a significant
      clinical effect in many neurological diseases. In the present report, we have
      developed a protocol for a scientific trial to analyze whether Xingnao Kaiqiao
      can be used to treat gastrointestinal dysfunction after laparoscopic surgery. In
      this context, we intend to execute a double-blind, randomized controlled trial to
      assess the efficacy and safety of Xingnao Kaiqiao acupuncture via intradermal
      needling. METHODS/DESIGN: This will be a single-center, double-blind, randomized
      controlled clinical trial. It has been designed on the basis of the Consolidated
      Standards of Reporting Trials (CONSORT 2010) guidelines and the Standards for
      Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). The
      subjects will be recruited from among inpatients scheduled for laparoscopic
      surgery at the Department of Minimally Invasive Surgery, Tianjin Nankai Hospital,
      Tianjin, China. Using random numbers generated in SPSS 19.0, the recruited
      subjects will be allocated to either the "Xingnao Kaiqiao" group or the sham
      stimulation group. A specially appointed investigator will be in charge of the
      randomization. Xingnao Kaiqiao via intradermal needling (or sham needling) will
      be administered 6 h after laparoscopic surgery, and then every 12 h for a total
      of six sessions, each of which will last 3 min. The subjects will undergo their
      first evaluation shortly before the first treatment (6 h after laparoscopic
      surgery); evaluations will be repeated every 12 h until a total of seven
      evaluations have been completed. The primary outcome will be the time until the
      first postoperative flatus. The secondary outcomes will be: the time until the
      first postoperative defecation; levels of abdominal pain, abdominal distension,
      and nausea; blood ghrelin level; occurrence of vomiting; psychological status;
      and quality of life. DISCUSSION: This upcoming randomized clinical trial was
      designed as a standardized method to assess the efficacy and safety of Xingnao
      Kaiqiao acupuncture using intradermal needles on PC6, DU26, and SP6 in the
      treatment of gastrointestinal dysfunction after laparoscopic surgery. We aim to
      provide evidence and thus improve the clinical application of this technique.
      TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-17010763 .
      Registered on 2 March 2017.

PMID- 29179762
TI  - Correction to: A novel protein derived from lamprey supraneural body tissue with
      efficient cytocidal actions against tumor cells.
AB  - CORRECTION: Unfortunately, following publication of this article [1], it was
      noticed that the key in Figure 5c incorrectly showed '0 h', '5 h' and '10 h'. The
      corrected version, showing '0 h', '12 h' and '24 h', can be seen below and the
      original article has been updated to reflect this.

PMID- 29179763
TI  - Whole transcriptome RNA-Seq analysis reveals extensive cell type-specific
      compartmentalization in Volvox carteri.
AB  - BACKGROUND: One of evolution's most important achievements is the development and
      radiation of multicellular organisms with different types of cells. Complex
      multicellularity has evolved several times in eukaryotes; yet, in most lineages,
      an investigation of its molecular background is considerably challenging since
      the transition occurred too far in the past and, in addition, these lineages
      evolved a large number of cell types. However, for volvocine green algae, such as
      Volvox carteri, multicellularity is a relatively recent innovation. Furthermore,
      V. carteri shows a complete division of labor between only two cell types -
      small, flagellated somatic cells and large, immotile reproductive cells. Thus, V.
      carteri provides a unique opportunity to study multicellularity and cellular
      differentiation at the molecular level. RESULTS: This study provides a whole
      transcriptome RNA-Seq analysis of separated cell types of the multicellular green
      alga V. carteri f. nagariensis to reveal cell type-specific components and
      functions. To this end, 246 million quality filtered reads were mapped to the
      genome and valid expression data were obtained for 93% of the 14,247 gene loci.
      In the subsequent search for protein domains with assigned molecular function, we
      identified 9435 previously classified domains in 44% of all gene loci.
      Furthermore, in 43% of all gene loci we identified 15,254 domains that are
      involved in biological processes. All identified domains were investigated
      regarding cell type-specific expression. Moreover, we provide further insight
      into the expression pattern of previously described gene families (e.g.,
      pherophorin, extracellular matrix metalloprotease, and VARL families). Our
      results demonstrate an extensive compartmentalization of the transcriptome
      between cell types: More than half of all genes show a clear difference in
      expression between somatic and reproductive cells. CONCLUSIONS: This study
      constitutes the first transcriptome-wide RNA-Seq analysis of separated cell types
      of V. carteri focusing on gene expression. The high degree of differential
      expression indicates a strong differentiation of cell types despite the fact that
      V. carteri diverged relatively recently from its unicellular relatives. Our
      expression dataset and the bioinformatic analyses provide the opportunity to
      further investigate and understand the mechanisms of cell type-specific
      expression and its transcriptional regulation.

PMID- 29179764
TI  - Routine blood tests are associated with short term mortality and can improve
      emergency department triage: a cohort study of >12,000 patients.
AB  - BACKGROUND: Prioritization of acutely ill patients in the Emergency Department
      remains a challenge. We aimed to evaluate whether routine blood tests can predict
      mortality in unselected patients in an emergency department and to compare risk
      prediction with a formalized triage algorithm. METHODS: A prospective
      observational cohort study of 12,661 consecutive admissions to the Emergency
      Department of Nordsjaelland University Hospital during two separate periods in
      2010 (primary cohort, n = 6279) and 2013 (validation cohort, n = 6383). Patients
      were triaged in five categories by a formalized triage algorithm. All patients
      with a full routine biochemical screening (albumin, creatinine, c-reactive
      protein, haemoglobin, lactate dehydrogenase, leukocyte count, potassium, and
      sodium) taken at triage were included. Information about vital status was
      collected from the Danish Central Office of Civil registration. Multiple logistic
      regressions were used to predict 30-day mortality. Validation was performed by
      applying the regression models on the 2013 validation cohort. RESULTS: Thirty-day
      mortality was 5.3%. The routine blood tests had a significantly stronger
      discriminative value on 30-day mortality compared to the formalized triage (AUC
      88.1 [85.7;90.5] vs. 63.4 [59.1;67.5], p < 0.01). Risk stratification by routine
      blood tests was able to identify a larger number of low risk patients (n = 2100,
      30-day mortality 0.1% [95% CI 0.0;0.3%]) compared to formalized triage (n = 1591,
      2.8% [95% CI 2.0;3.6%]), p < 0.01. CONCLUSIONS: Routine blood tests were strongly
      associated with 30-day mortality in acutely ill patients and discriminatory
      ability was significantly higher than with a formalized triage algorithm. Thus
      routine blood tests allowed an improved risk stratification of patients
      presenting in an emergency department.

PMID- 29179765
TI  - Using peer advocates to improve access to services among hard-to-reach
      populations with hepatitis C: a qualitative study of client and provider
      relationships.
AB  - BACKGROUND: Peer support programmes use individuals with specific experiences to
      improve engagement and outcomes among new clients. However, the skills and
      techniques used to achieve this engagement have not been mapped. This potentially
      restricts the development and replication of successful peer advocate models of
      care. This study explored how a group of peer advocates with experience of
      homelessness, alcohol and drug misuse made and sustained relationships with their
      client group. For the purposes of this project, the client group were located
      among a hepatitis C-positive cohort of people who have a history of injecting
      drug use and homelessness. METHODS: Five self-selecting advocates gave a
      narrative interview lasting 40-90 min. These interviews were double transcribed
      using both thematic analysis and narrative analysis in order to triangulate the
      data and provide a robust set of findings about the unique skills of peer
      advocates in creating and sustaining relationships with clients from hard-to
      reach populations. RESULTS: Peer advocates build rapport with clients through
      disclosing personal details about their lives. While this runs counter to
      assumptions about the need to maintain distance in client-patient relationships,
      the therapeutic benefits appear to outweigh the potential costs of this
      engagement. CONCLUSION: We conclude the therapeutic benefits of self-disclosure
      between peer advocates and their clients offer a moral grounding for self
      disclosure as a means of building relationships with key hard-to-reach
      populations.

PMID- 29179766
TI  - Workload of horses on a water treadmill: effect of speed and water height on
      oxygen consumption and cardiorespiratory parameters.
AB  - BACKGROUND: Despite the use of water treadmills (WT) in conditioning horses, the
      intensity of WT exercise has not been well documented. The workload on a WT is a
      function of water height and treadmill speed. Therefore, the purpose of this
      study was to determine the effects of these factors on workload during WT
      exercise. Fifteen client-owned Quarter Horses were used in a randomized,
      controlled study. Three belt speeds and three water heights (mid cannon, carpus
      and stifle), along with the control condition (dry treadmill, all three speeds),
      were tested. Measured outcomes were oxygen consumption (VO2), ventilation
      (respiratory frequency, tidal volume (VT)), heart rate (HR), and blood lactate.
      An ergospirometry system was used to measure VO2 and ventilation. Linear mixed
      effects models were used to examine the effects of presence or absence of water,
      water height and speed (as fixed effects) on measured outcomes. RESULTS: Water
      height and its interaction with speed had a significant effect on VO2, VT and HR,
      all peaking at the highest water level and speed (stifle at 1.39 m/s, median VO2
      = 16.70 ml/(kg.min), VT = 6 L, HR = 69 bpm). Respiratory frequency peaked with
      water at the carpus at 1.39 m/s (median 49 breaths/min). For a given water
      height, the small increments in speed did not affect the measured outcomes. Post
      exercise blood lactate concentration did not change. CONCLUSIONS: Varying water
      height and speed affects the workload associated with WT exercise. The conditions
      utilized in this study were associated with low intensity exercise. Water height
      had a greater impact on exercise intensity than speed.

PMID- 29179768
TI  - Correction to: Airplane pilot mental health and suicidal thoughts: a cross
      sectional descriptive study via anonymous web-based survey.
AB  - CORRECTION: After publication of the article [1], it has been brought to our
      attention that the specificity of the tool was reported as 88%. This specificity
      is for Major Depressive Disorder. The specificity of the tool for all depressive
      disorders, the outcome of interest in the study, is 93%.

PMID- 29179767
TI  - Rhabdomyolysis, lactic acidosis, and multiple organ failure during telbivudine
      treatment for hepatitis B: a case report and review of the literature.
AB  - BACKGROUND: Telbivudine can cause severe side effects, including myositis,
      neuritis, rhabdomyolysis, and lactic acidosis. However, reported cases of
      telbivudine leading to multiple organ failure are rare. Here, we report a case of
      telbivudine-induced severe polymyositis, lactic acidosis, and multiple organ
      failure. CASE PRESENTATION: A 30-year-old Chinese man with hepatitis B virus
      infection received antiviral treatment with 600 mg of telbivudine daily for more
      than 11 months. He developed progressive weakness and myalgia, and subsequently
      experienced palpitations, chest tightness, lethargy, hypotension, and hypoxemia.
      Blood tests showed markedly elevated levels of alanine aminotransferase (955
      U/L), aspartate aminotransferase (1375 U/L), blood urea nitrogen (14.9 mmol/L),
      creatine kinase (peak at 8050 U/L), and blood lactate (>20.0 mmol/L). His
      symptoms improved after continuous renal replacement therapy and short-term
      methylprednisolone treatment. Hyperbaric oxygen therapy, physical therapy, and
      rehabilitation for more than 2 months led to recovery of muscle strength to the
      normal range. CONCLUSIONS: We conclude that continuous renal replacement and
      steroid therapies play key roles in stabilizing telbivudine-induced severe
      rhabdomyolysis, lactic acidosis, and multiple organ failure. Hyperbaric oxygen,
      physical therapy, and rehabilitation may aid in functional recovery after the
      acute phase of lactic acidosis and organ failure.

PMID- 29179769
TI  - Catalogue of antibiotic resistome and host-tracking in drinking water deciphered
      by a large scale survey.
AB  - BACKGROUND: Excesses of antibiotic resistance genes (ARGs), which are regarded as
      emerging environmental pollutants, have been observed in various environments.
      The incidence of ARGs in drinking water causes potential risks to human health
      and receives more attention from the public. However, ARGs harbored in drinking
      water remain largely unexplored. In this study, we aimed at establishing an
      antibiotic resistome catalogue in drinking water samples from a wide range of
      regions and to explore the potential hosts of ARGs. RESULTS: A catalogue of
      antibiotic resistome in drinking water was established, and the host-tracking of
      ARGs was conducted through a large-scale survey using metagenomic approach. The
      drinking water samples were collected at the point of use in 25 cities in
      mainland China, Hong Kong, Macau, Taiwan, South Africa, Singapore and the USA. In
      total, 181 ARG subtypes belonging to 16 ARG types were detected with an abundance
      range of 2.8 * 10-2 to 4.2 * 10-1 copies of ARG per cell. The highest abundance
      was found in northern China (Henan Province). Bacitracin, multidrug,
      aminoglycoside, sulfonamide, and beta-lactam resistance genes were dominant in
      drinking water. Of the drinking water samples tested, 84% had a higher ARG
      abundance than typical environmental ecosystems of sediment and soil. Metagenomic
      assembly-based host-tracking analysis identified Acidovorax, Acinetobacter,
      Aeromonas, Methylobacterium, Methyloversatilis, Mycobacterium, Polaromonas, and
      Pseudomonas as the hosts of ARGs. Moreover, potential horizontal transfer of ARGs
      in drinking water systems was proposed by network and Procrustes analyses.
      CONCLUSIONS: The antibiotic resistome catalogue compiled using a large-scale
      survey provides a useful reference for future studies on the global surveillance
      and risk management of ARGs in drinking water. .

PMID- 29179770
TI  - Fertility outcomes following obstetric fistula repair: a prospective cohort
      study.
AB  - BACKGROUND: Obstetric fistula (OF) is a maternal morbidity associated with high
      rates of stillbirth, amenorrhea, and sexual dysfunction. Limited data exists on
      the reproductive outcomes of women in the years following a fistula repair. The
      objective of this study is to describe the fertility outcomes and family planning
      practices in a population of Malawian women 1-4 years after fistula repair.
      METHODS: Women who had enrolled into a clinical database of OF patients and
      undergone OF repair between January 1, 2012 and July 31, 2014 were recruited and
      enrolled to complete a home-based survey of their demographic and reproductive
      health data 1-4 years after their repair. Pregnancy, amenorrhea, and sexual
      function were described using frequency analysis, and we compared antimullerian
      hormone (AMH) concentrations between women with menses or pregnancy with women
      with amenorrhea or no pregnancy using Wilcoxon rank sum tests. RESULTS: Of 297
      women with a prior OF repair, 148 had reproductive potential and were included in
      this analysis. Overall 30 women of these women (21%) became pregnant since their
      fistula repair, with most pregnancies ending with cesarean delivery. Of the 32
      women who were amenorrheic at the time of repair, 25 (78.1%) had resumption of
      menses. Only 11 (8.6%) of sexually active women reported dyspareunia, and among
      women who were not trying to conceive, 53.1% were currently using a method of
      family planning. No significant differences were found in AMH concentrations
      between those who were pregnant or had menses versus those without pregnancy or
      menses, respectively. CONCLUSIONS: In this long-term follow-up study of women
      after OF repair, many women were able to achieve a pregnancy with a live birth,
      have normal menses, be sexually active, and access contraception. These
      achievements will further assist a population of women whose reintegration and
      restoration of dignity is closely tied to their ability to achieve their
      reproductive goals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT02685878 .

PMID- 29179771
TI  - Paracrine effects of human amniotic epithelial cells protect against chemotherapy
      induced ovarian damage.
AB  - BACKGROUND: Human amniotic epithelial cells (hAECs) are attractive candidates for
      regenerative medical therapy, with the potential to replace deficient cells and
      improve functional recovery after injury. Previous studies have demonstrated that
      transplantation of hAECs effectively alleviate chemotherapy-induced ovarian
      damage via inhibiting granulose cells apoptosis in animal models of premature
      ovarian failure/insufficiency (POF/POI). However, the underlying molecular
      mechanism accounting for hAECs-mediated ovarian function recovery is not fully
      understood. METHODS: To investigate whether hAECs-secreting cytokines act as
      molecular basis to attenuate chemotherapy-induced ovarian injury, hAECs or hAEC
      conditioned medium (hAEC-CM) was injected into the unilateral ovary of POF/POI
      mouse. Follicle development was evaluated by H&E staining at 1, 2 months after
      hAECs or hAEC-CM treatment. In addition, we performed a cytokine array containing
      507 human cytokines on hAECs-derived serum-free conditioned medium. Finally, we
      further investigated whether hAECs could affect chemotherapy-induced apoptosis in
      primary human granulosa-lutein (hGL) cells and the tube formation of human
      umbilical vein endothelial cells (hUVECs) via a co-culture system in vitro.
      RESULTS: We observed the existence of healthy and mature follicles in ovaries
      treated with hAECs or hAEC-CM, whereas seriously fibrosis and many atretic
      follicles were found in the contralateral untreated ovaries of the same mouse. To
      distinguish cytokines involved in the process of hAECs-restored ovarian function,
      hAEC-CM was analyzed with a human cytokines array. Results revealed that 109
      cytokines in hAEC-CM might participate in a variety of biological processes
      including apoptosis, angiogenesis, cell cycle and immune response. In vitro
      experiments, hAECs significantly inhibited chemotherapy-induced apoptosis and
      activated TGF-beta/Smad signaling pathway within primary granulosa-lutein cells
      in paracrine manner. Furthermore, hAEC-CM was shown to promote angiogenesis in
      the injured ovaries and enhance the tube formation of human umbilical vein
      endothelial cells (hUVECs) in co-culture system. CONCLUSIONS: These findings
      demonstrated that paracrine might be a key pathway in the process of hAECs
      mediating ovarian function recovery in animal models of premature ovarian
      failure/insufficiency (POF/POI).

PMID- 29179773
TI  - Sustained inflations versus UK standard inflations during initial resuscitation
      of prematurely born infants in the delivery room: a study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Many infants born at less than 34 weeks of gestational age will
      require resuscitation in the delivery suite. Yet, different resuscitation
      techniques are specified in different national guidelines, likely reflecting a
      limited evidence base. One difference is the length of mechanical inflation
      initially delivered to infants either via a facemask or endotracheal tube. Some
      guidelines specify short inflations delivered at rates of 40-60/min, others
      recommend initial inflations lasting 2-3 s or sustained inflations lasting for >=
      5 s for initial resuscitation. Research has shown that tidal volumes > 2.2 mL/kg
      (the anatomical dead space) are seldom generated unless the infant's respiratory
      effort coincides with an inflation (active inflation). When inflations lasting 1
      3 s were used, the time to the first active inflation was inversely proportional
      to the inflation time. This trial investigates whether a sustained inflation or
      repeated shorter inflations is more effective in stimulating the first active
      inflation. METHODS: This non-blinded, randomised controlled trial performed at a
      single tertiary neonatal unit is recruiting 40 infants born at < 34 weeks of
      gestational age. A 15-s sustained inflation is being compared to five repeated
      inflations of 2-3 s during the resuscitation at delivery. A respiratory function
      monitor is used to record airway pressure, flow, expiratory tidal volume and end
      tidal carbon dioxide (ETCO2) levels. The study is performed as emergency research
      without prior consent and was approved by the NHS London-Riverside Research
      Ethics Committee. The primary outcome is the minute volume in the first minute of
      resuscitation with secondary outcomes of the time to the first active inflation
      and ETCO2 level during the first minute of recorded resuscitation. DISCUSSION:
      This is the first study to compare a sustained inflation to the current UK
      practice of five initial inflations of 2-3 s. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02967562 . Registered on 15 November 2016.

PMID- 29179772
TI  - Recurrent de novo mutations in neurodevelopmental disorders: properties and
      clinical implications.
AB  - Next-generation sequencing (NGS) is now more accessible to clinicians and
      researchers. As a result, our understanding of the genetics of neurodevelopmental
      disorders (NDDs) has rapidly advanced over the past few years. NGS has led to the
      discovery of new NDD genes with an excess of recurrent de novo mutations (DNMs)
      when compared to controls. Development of large-scale databases of normal and
      disease variation has given rise to metrics exploring the relative tolerance of
      individual genes to human mutation. Genetic etiology and diagnosis rates have
      improved, which have led to the discovery of new pathways and tissue types
      relevant to NDDs. In this review, we highlight several key findings based on the
      discovery of recurrent DNMs ranging from copy number variants to point mutations.
      We explore biases and patterns of DNM enrichment and the role of mosaicism and
      secondary mutations in variable expressivity. We discuss the benefit of whole
      genome sequencing (WGS) over whole-exome sequencing (WES) to understand more
      complex, multifactorial cases of NDD and explain how this improved understanding
      aids diagnosis and management of these disorders. Comprehensive assessment of the
      DNM landscape across the genome using WGS and other technologies will lead to the
      development of novel functional and bioinformatics approaches to interpret DNMs
      and drive new insights into NDD biology.

PMID- 29179774
TI  - A 10-year surveillance of Rickettsiales (Rickettsia spp. and Anaplasma
      phagocytophilum) in the city of Hanover, Germany, reveals Rickettsia spp. as
      emerging pathogens in ticks.
AB  - BACKGROUND: Rickettsiales (Rickettsia spp. and Anaplasma phagocytophilum)
      transmitted by ticks are considered (re-)emerging pathogens posing a risk to
      public health. Nevertheless, year-long monitoring studies on prevalences of these
      pathogens in questing ticks to contribute to public health risk assessment are
      rare. METHODS: The current study extends previous prevalence surveillances (2005
      and 2010) by 2015 to a 10-year monitoring. Therefore, 2100 questing Ixodes
      ricinus were collected from April to October 2015 at ten different recreation
      sites in the city of Hanover, Germany, to determine potential changes in tick
      infection rates with Rickettsiales. RESULTS: Of the collected ticks, 288 were
      adult females, 285 adult males and 1527 nymphs. Overall, 3.8% (79/2100) of ticks
      were infected with A. phagocytophilum, 50.8% (1066/2100) with Rickettsia spp. and
      2.2% (46/2100) with both pathogens. Statistical analyses revealed stagnating A.
      phagocytophilum infection rates over the 10-year monitoring period, whereas
      Rickettsia infections increased significantly (33.3% in 2005 and 26.2% in 2010 vs
      50.8% in 2015). This increase was also characterized by prominent seasonality
      with higher prevalences from July to October. CONCLUSIONS: As increased tick
      infection rates result in an increased risk for public health, the long-term data
      reported here provide significant implications for the understanding of
      progressing Rickettsiales distribution in ticks and essentially contribute to
      reliable public health risk assessments.

PMID- 29179775
TI  - Fusobacterium emphysematous pyomyositis with necrotizing fasciitis of the leg
      presenting as compartment syndrome: a case report.
AB  - BACKGROUND: Fusobacterium necrophorum is a common agent of disease in humans, but
      the occurrence of primary infections outside the head and neck area is extremely
      rare. While infection with Fusobacterium necrophorum has a rather benign course
      above the thorax, the organism is capable of producing very severe disease when
      located in unusual sites, including various forms of septic thrombophlebitis. No
      infections of the leg have been documented before; thus, antibiotic coverage for
      Fusobacterium is currently not recommended in this area. CASE PRESENTATION: A 50
      year-old homeless African-American man presented complaining of severe pain in
      his right lower extremity. A clinical workup was consistent with emphysematous
      pyomyositis and compartment syndrome; he received limb-saving surgical
      intervention. The offending organism was identified as Fusobacterium necrophorum,
      and the antibiotic coverage was adjusted accordingly. CONCLUSIONS: Bacteria
      typically involved in necrotizing infections of the lower extremity include Group
      A beta-hemolytic Streptococcus, Clostridium perfringens, and common anaerobic
      bacteria (Bacteroides, Peptococcus, and Peptostreptococcus). This case report
      presents a case of gas gangrene of the leg caused by Fusobacterium necrophorum,
      the first such case reported. Fusobacterium should now be included in the
      differential diagnosis of necrotizing fasciitis of the extremities.

PMID- 29179776
TI  - Translation and cultural adaptation of the CLEFT-Q for use in Colombia, Chile,
      and Spain.
AB  - BACKGROUND: Cleft lip and/or palate (CL/P) is a common congenital craniofacial
      anomaly that may negatively affect an individual's appearance, health-related
      quality of life, or speech. In Spain, Colombia, and Chile the overall prevalence
      of CL/P ranges from 0.53 to 1.59 cases per 1000 live births. Currently, there is
      no patient-reported outcome (PRO) instrument that is specific for patients with
      CL/P. The CLEFT-Q is a new PRO instrument developed to measure outcomes of
      treatment in patients 8 to 29 years of age with CL/P. The aim of this study was
      to translate and culturally adapt the CLEFT-Q for use in Colombia, Chile, and
      Spain. METHODS: The CLEFT-Q was translated from English to 3 Spanish language
      varieties (Colombian, Chilean, and Spanish (Spain)) and Catalan. Translation and
      cultural adaptation guidelines set forth by the International Society for
      Pharmacoeconomics and Outcomes Research were followed. RESULTS: The field- test
      version of the CLEFT-Q consisted of 13 scales (total 154 items) measuring
      appearance, health-related quality of life, and facial function. Forward
      translations revealed 10 (7%) items that were difficult to translate into
      Chilean, and back translations identified 34 (22%) and 21 (13%) items whose
      meaning differed from the English version in at least 1 of the 3 Spanish
      varieties and Catalan respectively. Twenty-one participants took part in
      cognitive debriefing interviews. Participants were recruited from plastic surgery
      centres in Bogota, Colombia (n = 4), Santiago, Chile (n = 7), and Barcelona,
      Spain (n = 10). Most participants were males (n = 14, 67%) and were diagnosed
      with CL/P (n = 17, 81%). Participants reported difficulty understanding 1 item in
      the Colombian, 1 item in the Spanish (Spain), and 11 items from the Catalan
      version. Comparison of the 3 Spanish varieties revealed 61 (40%) of the 154 items
      whose wording differed across the 3 Spanish versions. CONCLUSION: Translation and
      cultural adaptation processes provided evidence of transferability of the CLEFT-Q
      scales into 3 Spanish varieties and Catalan, as semantic, idiomatic,
      experiential, and conceptual equivalence of the items, instructions, and response
      options were achieved.

PMID- 29179777
TI  - A document-centric approach for developing the tolAPC ontology.
AB  - BACKGROUND: There are many challenges associated with ontology building, as the
      process often touches on many different subject areas; it needs knowledge of the
      problem domain, an understanding of the ontology formalism, software in use and,
      sometimes, an understanding of the philosophical background. In practice, it is
      very rare that an ontology can be completed by a single person, as they are
      unlikely to combine all of these skills. So people with these skills must
      collaborate. One solution to this is to use face-to-face meetings, but these can
      be expensive and time-consuming for teams that are not co-located. Remote
      collaboration is possible, of course, but one difficulty here is that domain
      specialists use a wide-variety of different "formalisms" to represent and share
      their data - by the far most common, however, is the "office file" either in the
      form of a word-processor document or a spreadsheet. Here we describe the
      development of an ontology of immunological cell types; this was initially
      developed by domain specialists using an Excel spreadsheet for collaboration. We
      have transformed this spreadsheet into an ontology using highly-programmatic and
      pattern-driven ontology development. Critically, the spreadsheet remains part of
      the source for the ontology; the domain specialists are free to update it, and
      changes will percolate to the end ontology. RESULTS: We have developed a new
      ontology describing immunological cell lines built by instantiating ontology
      design patterns written programmatically, using values from a spreadsheet
      catalogue. CONCLUSIONS: This method employs a spreadsheet that was developed by
      domain experts. The spreadsheet is unconstrained in its usage and can be freely
      updated resulting in a new ontology. This provides a general methodology for
      ontology development using data generated by domain specialists.

PMID- 29179778
TI  - Determining requirements for patient-centred care: a participatory concept
      mapping study.
AB  - BACKGROUND: Recognition of a need for patient-centred care is not new, however
      making patient-centred care a reality remains a challenge to organisations. We
      need empirical studies to extend current understandings, create new
      representations of the complexity of patient-centred care, and guide collective
      action toward patient-centred health care. To achieve these ends, the research
      aim was to empirically determine what organisational actions are required for
      patient-centred care to be achieved. METHODS: We used an established
      participatory concept mapping methodology. Cross-sector stakeholders contributed
      to the development of statements for patient-centred care requirements, sorting
      statements into groupings according to similarity, and rating each statement
      according to importance, feasibility, and achievement. The resultant data were
      analysed to produce a visual concept map representing participants'
      conceptualisation of patient-centred care requirements. Analysis included the
      development of a similarity matrix, multidimensional scaling, hierarchical
      cluster analysis, selection of the number of clusters and their labels,
      identifying overarching domains and quantitative representation of rating data.
      RESULTS: The outcome was the development of a conceptual map for the Requirements
      of Patient-Centred Care Systems (ROPCCS). ROPCCS incorporates 123 statements
      sorted into 13 clusters. Cluster labels were: shared responsibility for
      personalised health literacy; patient provider dynamic for care partnership;
      collaboration; shared power and responsibility; resources for coordination of
      care; recognition of humanity - skills and attributes; knowing and valuing the
      patient; relationship building; system review evaluation and new models;
      commitment to supportive structures and processes; elements to facilitate change;
      professional identity and capability development; and explicit education and
      learning. The clusters were grouped into three overarching domains, representing
      a cross-sectoral approach: humanity and partnership; career spanning education
      and training; and health systems, policy and management. Rating of statements
      allowed the generation of go-zone maps for further interrogation of the relative
      importance, feasibility, and achievement of each patient-centred care requirement
      and cluster. CONCLUSION: The study has empirically determined requirements for
      patient-centred care through the development of ROPCCS. The unique map emphasises
      collaborative responsibility of stakeholders to ensure that patient-centred care
      is comprehensively progressed. ROPCCS allows the complex requirements for patient
      centred care to be understood, implemented, evaluated, measured, and shown to be
      occurring.

PMID- 29179779
TI  - Evaluation of in silico algorithms for use with ACMG/AMP clinical variant
      interpretation guidelines.
AB  - BACKGROUND: The American College of Medical Genetics and American College of
      Pathologists (ACMG/AMP) variant classification guidelines for clinical reporting
      are widely used in diagnostic laboratories for variant interpretation. The
      ACMG/AMP guidelines recommend complete concordance of predictions among all in
      silico algorithms used without specifying the number or types of algorithms. The
      subjective nature of this recommendation contributes to discordance of variant
      classification among clinical laboratories and prevents definitive classification
      of variants. RESULTS: Using 14,819 benign or pathogenic missense variants from
      the ClinVar database, we compared performance of 25 algorithms across datasets
      differing in distinct biological and technical variables. There was wide
      variability in concordance among different combinations of algorithms with
      particularly low concordance for benign variants. We also identify a previously
      unreported source of error in variant interpretation (false concordance) where
      concordant in silico predictions are opposite to the evidence provided by other
      sources. We identified recently developed algorithms with high predictive power
      and robust to variables such as disease mechanism, gene constraint, and mode of
      inheritance, although poorer performing algorithms are more frequently used based
      on review of the clinical genetics literature (2011-2017). CONCLUSIONS: Our
      analyses identify algorithms with high performance characteristics independent of
      underlying disease mechanisms. We describe combinations of algorithms with
      increased concordance that should improve in silico algorithm usage during
      assessment of clinically relevant variants using the ACMG/AMP guidelines.

PMID- 29179780
TI  - A highly transmissible tuberculosis outbreak: the importance of bars.
AB  - The transmission of tuberculosis (TB) in bars is difficult to study. The
      objective was to describe a large TB outbreak in a company's bar and other
      leisure settings. A descriptive study of a TB outbreak was carried out. Contacts
      were studied in the index case's workplace bar (five circles of contacts) and
      other recreational areas (social network of three bars in the index case's
      neighbourhood). Chest X-rays were recommended to contacts with positive
      tuberculin skin tests (TST) (?5 mm). The risk of latent tuberculosis infection
      (LTBI) was determined using an adjusted odds ratio. The dose-response
      relationship was determined using the chi-square test for linear trend. We
      studied 316 contacts at the index case's workplace and detected five new cases of
      TB. The prevalence of LTBI was 57.9% (183/316) and was higher in the first
      circle, 96.0% (24/25), and lower in the fifth, 46.5% (20/43) (P < 0.0001). Among
      58 contacts in the three neighbourhood bars, two TB cases were detected and the
      LTBI prevalence was 51.7% (30/58). Two children of one secondary TB company
      patient became ill. Bars may be transmission locations for TB and, as they are
      popular venues for social events, should be considered as potential areas of
      exposure.

PMID- 29179782
TI  - Invited commentary in response to the paper entitled 'Iodine concentration of
      milk-alternative drinks available in the UK in comparison with cows' milk' by
      Sarah Bath and colleagues.

PMID- 29179781
TI  - Low-fat yogurt consumption reduces biomarkers of chronic inflammation and
      inhibits markers of endotoxin exposure in healthy premenopausal women: a
      randomised controlled trial.
AB  - The anti-inflammatory mechanisms of low-fat dairy product consumption are largely
      unknown. The objective of this study was to determine whether low-fat yogurt
      reduces biomarkers of chronic inflammation and endotoxin exposure in women.
      Premenopausal women (BMI 18.5-27 and 30-40 kg/m2) were randomised to consume 339
      g of low-fat yogurt (yogurt non-obese (YN); yogurt obese (YO)) or 324 g of soya
      pudding (control non-obese; control obese (CO)) daily for 9 weeks (n 30/group).
      Fasting blood samples were analysed for IL-6, TNF-alpha/soluble TNF II (sTNF
      RII), high-sensitivity C-reactive protein, 2-arachidonoyl glycerol, anandamide,
      monocyte gene expression, soluble CD14 (sCD14), lipopolysaccharide (LPS), LPS
      binding protein (LBP), IgM endotoxin-core antibody (IgM EndoCAb), and zonulin.
      BMI, waist circumference and blood pressure were also determined. After 9-week
      yogurt consumption, YO and YN had decreased TNF-alpha/sTNFR-RII. Yogurt
      consumption increased plasma IgM EndoCAb regardless of obesity status. sCD14 was
      not affected by diet, but LBP/sCD14 was lowered by yogurt consumption in both YN
      and YO. Yogurt intervention increased plasma 2-arachidonoylglycerol in YO but not
      YN. YO peripheral blood mononuclear cells expression of NF-kappaB inhibitor alpha
      and transforming growth factor beta1 increased relative to CO at 9 weeks. Other
      biomarkers were unchanged by diet. CO and YO gained approximately 0.9 kg in body
      weight. YO had 3.6 % lower diastolic blood pressure at week 3. Low-fat yogurt for
      9 weeks reduced biomarkers of chronic inflammation and endotoxin exposure in
      premenopausal women compared with a non-dairy control food. This trial was
      registered as NCT01686204.

PMID- 29179783
TI  - A "Stone in the Pond" Approach to Contact Tracing: Responding to a Large-Scale,
      Nosocomial Tuberculosis Exposure in a Moderate TB-Burden Setting.
AB  - A "stone in the pond" strategy is a practical approach to investigating large
      scale nosocomial tuberculosis (TB) exposures. Here, we describe such a risk
      stratified approach to contact tracing after a TB exposure that occurred over 5
      months in a pediatric inpatient ward in a country with a moderate TB burden.
      Infect Control Hosp Epidemiol 2017;38:1509-1511.

PMID- 29179784
TI  - Underweight increases the risk of early death in tuberculosis patients.
AB  - Evidence regarding the association between BMI and mortality in tuberculosis (TB)
      patients is limited and inconsistent. We investigated the impact of BMI on TB
      specific and non-TB-specific mortality with respect to different timing of death.
      All Taiwanese adults with TB in Taipei were included in a retrospective cohort
      study in 2012-2014. Multinomial Cox proportional hazards regression was used to
      evaluate the associations between BMI, cause-specific mortality and timing of
      death. Of 2410 eligible patients, 86.0 % (2061) were successfully treated, and TB
      specific and non-TB-specific mortality occurred for 2.2 % (54) and 13.9 % (335),
      respectively. After controlling for potential confounders, underweight was
      significantly associated with a higher risk of all-cause mortality (adjusted
      hazard ratio (AHR) 1.57; 95 % CI 1.26, 1.95), whereas overweight was not. When
      cause-specific death was considered, underweight was associated with an increased
      risk of either TB-specific (AHR 1.85; 95 % CI 1.03, 3.33) or non-TB-specific
      death (AHR 1.52; 95 % CI 1.19, 1.95) during treatment. With joint consideration
      of cause-specific and timing of death, underweight only significantly increased
      the risk of TB-specific (AHR 2.23; 95 % CI 1.09, 4.59) and non-TB-specific
      mortality (AHR 1.81; 95 % CI 1.29, 2.55) within the first 8 weeks of treatment.
      This study suggests that underweight increases the risk of early death in TB
      patients during treatment.

PMID- 29179785
TI  - Toxoplasma gondii reorganizes the host cell architecture during spontaneous cyst
      formation in vitro.
AB  - Toxoplasma gondii is an intracellular protozoan parasite that causes
      toxoplasmosis, a prevalent infection related to abortion, ocular diseases and
      encephalitis in immuno-compromised individuals. In the untreatable (and life
      long) chronic stage of toxoplasmosis, parasitophorous vacuoles (PVs, containing
      T. gondii tachyzoites) transform into tissue cysts, containing slow-dividing
      bradyzoite forms. While acute-stage infection with tachyzoites involves global
      rearrangement of the host cell cytoplasm, focused on favouring tachyzoite
      replication, the cytoplasmic architecture of cells infected with cysts had not
      been described. Here, we characterized (by fluorescence and electron microscopy)
      the redistribution of host cell structures around T. gondii cysts, using a T.
      gondii strain (EGS) with high rates of spontaneous cystogenesis in vitro.
      Microtubules and intermediate filaments (but not actin microfilaments) formed a
      'cage' around the cyst, and treatment with taxol (to inhibit microtubule
      dynamics) favoured cystogenesis. Mitochondria, which appeared adhered to the PV
      membrane, were less closely associated with the cyst wall. Endoplasmic reticulum
      (ER) profiles were intimately associated with folds in the cyst wall membrane.
      However, the Golgi complex was not preferentially localized relative to the cyst,
      and treatment with tunicamycin or brefeldin A (to disrupt Golgi or ER function,
      respectively) had no significant effect on cystogenesis. Lysosomes accumulated
      around cysts, while early and late endosomes were more evenly distributed in the
      cytoplasm. The endocytosis tracer HRP (but not BSA or transferrin) reached
      bradyzoites after uptake by infected host cells. These results suggest that T.
      gondii cysts reorganize the host cell cytoplasm, which may fulfil specific
      requirements of the chronic stage of infection.

PMID- 29179786
TI  - A chemical compound based on methylxanthine-polyphenols lowers nitric oxide
      levels and increases post-thaw human sperm viability.
AB  - We produced a new chemical compound based on methylxanthines and polyphenols
      (CCMP) present in the chemical matrix of guarana (Paullinia cupana), a seed
      extract with antioxidant properties. After supplementation with the standard
      extract of resveratrol, a well documented antioxidant found in other plant
      sources, we investigated whether this resveratrol-enriched compound could improve
      sperm viability and modulate differentially reactive oxygen species (ROS) and
      nitric oxide (NO) levels in thawed sperm. Sperm samples obtained from healthy
      young donors were treated with different concentrations of guarana extract (0.1,
      1, 5 or 10 mg/ml) and cells were frozen at -80 degrees C for 24 h. In addition,
      the potential protective effects of guarana treatment on sperm treated with pro
      oxidant compound (200 uM hydrogen peroxide, H2O2) were assessed. Samples were
      also exposed to three concentrations of CCMP before being frozen in liquid
      nitrogen (-196 degrees C) or in an ultrafreezer (-80 degrees C) for 24 h, and
      both pre-freezing and post-thaw measurements of viability and oxidative stress
      were performed. Guarana supplementation at 10 mg/ml significantly increased post
      thaw viability and decreased oxidative metabolism of the sperm. Moreover,
      selected concentrations of CCMP improved viability and oxidative metabolism in
      sperm samples pre-freezing. Furthermore, CCMP showed cryoprotective activity by
      increasing viability and decreasing oxidative stress in post-thaw samples. In
      summary, these findings suggested that CCMP supplementation acts as a
      cryoprotectant to modulate ROS and NO levels in thawed sperm. CCMP could be used
      to enhance sperm quality and reproductive success.

PMID- 29179787
TI  - Sperm-derived factors enhance the in vitro developmental potential of haploid
      parthenotes.
AB  - Parthenotes are characterized by poor in vitro developmental potential either due
      to the ploidy status or the absence of paternal factors. In the present study, we
      demonstrate the beneficial role of sperm-derived factors (SDF) on the in vitro
      development of mouse parthenotes. Mature (MII) oocytes collected from
      superovulated Swiss albino mice were activated using strontium chloride (SrCl2)
      in the presence or absence of various concentrations of SDF in M16 medium. The
      presence of SDF in activation medium did not have any significant influence on
      the activation rate. However, a significant increase in the developmental
      potential of the embryos and increased blastocyst rate (P < 0.01) was observed at
      50 ug/ml concentration. Furthermore, the activated oocytes from this group
      exhibited early cleavage and cortical distribution of cortical granules that was
      similar to that of normally fertilized zygotes. Culturing 2-cell stage
      parthenotes in the presence of SDF significantly improved the developmental
      potential (P < 0.05) indicating that they also play a significant role in embryo
      development. In conclusion, artificial activation of oocytes with SDF can improve
      the developmental potential of parthenotes in vitro.

PMID- 29179789
TI  - A case of mistaken identity? - CORRIGENDUM.

PMID- 29179788
TI  - X-ray micro-computed tomography (MUCT): an emerging opportunity in parasite
      imaging.
AB  - X-ray micro-computed tomography (MUCT) is a technique which can obtain three
      dimensional images of a sample, including its internal structure, without the
      need for destructive sectioning. Here, we review the capability of the technique
      and examine its potential to provide novel insights into the lifestyles of
      parasites embedded within host tissue. The current capabilities and limitations
      of the technology in producing contrast in soft tissues are discussed, as well as
      the potential solutions for parasitologists looking to apply this technique. We
      present example images of the mouse whipworm Trichuris muris and discuss the
      application of MUCT to provide unique insights into parasite behaviour and
      pathology, which are inaccessible to other imaging modalities.

PMID- 29179790
TI  - Mobile phone usage does not affect sudden sensorineural hearing loss.
AB  - OBJECTIVE: Recent studies found that mobile phone users had a significantly
      greater risk of having elevated thresholds in speech frequencies. This study
      investigated the correlation between the laterality of sudden sensorineural
      hearing loss, handedness and the preferred ear for mobile phone use. METHODS: The
      study included all patients who presented with sudden sensorineural hearing loss
      to the Department of Otolaryngology - Head and Neck Surgery in our tertiary
      referral medical centre between 2014 and 2016. Patients were asked to indicate
      their dominant hand and preferred ear for mobile phone use. RESULTS: The study
      comprised 160 patients. No correlation was found between the dominant hand or
      preferred ear for mobile phone use and the side of sudden sensorineural hearing
      loss. There was no correlation between the side of the sudden sensorineural
      hearing loss (preferable or non-preferable for mobile phone use) and audiometric
      characteristics. CONCLUSION: No correlation was found between the laterality of
      ears used for mobile phone and sudden sensorineural hearing loss.

PMID- 29179791
TI  - Influence of parasite load on the diagnosis and occurrence of eosinophilia in
      alcoholic patients infected with Strongyloides stercoralis.
AB  - Alcoholic patients are more susceptible to Strongyloides stercoralis infection.
      The chronic use of alcohol raises the levels of endogenous corticosteroids, which
      regulates the development of larvae and stimulates the differentiation of
      rhabditiform into infective filariform larvae, thus inducing internal
      autoinfection. Therefore, early diagnosis is important to prevent severe
      strongyloidiasis. The aim of this study was to evaluate the efficacy of
      parasitological methods, according to the parasite load and the number of stool
      samples, for diagnosis of S. stercoralis infection, as well the peripheral blood
      eosinophil count in alcoholic patients. A total of 330 patients were included in
      this study. The diagnosis was established using three parasitological methods:
      agar plate culture, Baermann-Moraes method and spontaneous sedimentation.
      Peripheral eosinophilia was considered when the level was >600 eosinophils/mm3.
      The agar plate culture (APC) had the highest sensitivity (97.3%). However, the
      analysis of multiple samples increased the sensitivity of all parasitological
      methods. The sensitivities of the methods were influenced by the parasite load.
      When the larval number was above 10, the sensitivity of APC was 100%, while in
      spontaneous sedimentation the sensitivity reached 100% when the larval number was
      above 50. In the present study, 15.4% of alcoholic patients infected with S.
      stercoralis (12/78) had increased peripheral blood eosinophil count (above 600
      eosinophils/mm3). For an efficient parasitological diagnosis of S. stercoralis
      infection in alcoholic patients, repeated examination by two parasitological
      methods must be recommended, including agar plate culture due to its higher
      sensitivity. Moreover, S. stercoralis infection was associated with eosinophilia,
      mostly in patients excreting up to 10 larvae/g faeces.

PMID- 29179793
TI  - Science news.

PMID- 29179795
TI  - Events diary.

PMID- 29179794
TI  - One hundred years ago in Science Progress . . .

PMID- 29179796
TI  - Postscript to the special issue commemorating Volume 100 of Science Progress.

PMID- 29179798
TI  - Perovskite Solar Cells Research in Switzerland.

PMID- 29179799
TI  - Additives, Hole Transporting Materials and Spectroscopic Methods to Characterize
      the Properties of Perovskite Films.
AB  - The achievement of high efficiency and high stability in perovskite solar cells
      (PSCs) requires optimal selection and evaluation of the various components. After
      a brief introduction to the perovskite materials and their historical evolution,
      the first part is devoted to the hole transporting material (HTM), between
      photoelectrode and dark counter electrode. The basic requirements for an
      efficient HTM are stated. Subsequently, the most used HTM, spiro-OMeTAD, is
      compared to alternative HTMs, both small-molecule size species and electronically
      conducting polymers. The second part is devoted to additives related to the
      performance of the perovskite light-absorbing material itself. These are related
      either to the modification of the composition of the material itself or to the
      optimization of the morphology during the perovskite preparation stage, and their
      effect is in the enhancement of the power conversion efficiency, the long-term
      stability, or the reproducibility of the properties of the PSCs. Finally, a
      number of spectroscopic methods based on the UV-Vis part of the electromagnetic
      spectrum useful for characterizing the different perovskite material types are
      described in the last part of this review.

PMID- 29179800
TI  - Ionic Liquids: From Synthesis to Applications in Solar Cells.
AB  - Ionic liquids continue to find applications in an ever-increasing range of
      technologies. Here we describe some of the key routes used to prepare ionic
      liquids and then relate their properties to their applications. In particular,
      ionic liquids have been used to facilitate crystal growth and, for this reason,
      are emerging as useful solvents/additives in the preparation of perovskite films.
      The role of ionic liquids in these films and how they lead to perovskite solar
      cells with high efficiencies and stabilities is described.

PMID- 29179801
TI  - Time-resolved Element-selective Probing of Charge Carriers in Solar Materials.
AB  - We review our recent results on the implementation of picosecond (ps) X-ray
      absorption spectroscopy to probe the electronic and geometric structure of
      centres formed by photoexcitation of solar materials such as TiO2 polymorphs and
      inorganic Cs-based perovskites. The results show electron localization at Ti
      defects in TiO2 anatase and rutile and small hole polaron formation in the
      valence band of CsPbBr3, all within 80 ps. This method is promising for the study
      of the ultrafast time scales of such processes, especially with the advent of the
      Swiss X-ray Free Electron Laser (SwissFEL).

PMID- 29179802
TI  - Synthesis, Characterization of Zinc Complexes with Neutral alpha-Diimine Ligands
      and Application in Ring-opening Polymerization of epsilon-Caprolactone.
AB  - A series of neutral alpha-diimine ligands with diacetyl and acenaphthenequinone
      skeletons were prepared by the reaction between diacetyl and the corresponding
      aromatic amine. These ligands reacted with ZnCl2 to generate symmetric alpha
      diimine zinc complexes C1-C10. Experimental results indicated that the alpha
      diimine zinc complexes with a diacetyl skeleton (C1-C4) were active in ring
      opening polymerization (ROP) of epsilon-caprolactone (epsilon-CL). The complexes
      with an acenaphthenequinone skeleton showed a small steric effect (C5, C8 and C9)
      but the complex substituted with an electron-withdrawing group (C10) showed high
      activity in the monomer conversion rate during ROP of epsilon-CL. The ROP
      catalysts of epsilon-CL demonstrated the mechanism of monomer activation in the
      presence of benzyl alcohol.

PMID- 29179806
TI  - Summer School 2017 - Exchange of Ideas for Biologists.
AB  - When Daniel Gygax, former President of Swiss biotechnet, and Letizia Vittorelli
      from the University of Palermo had the idea in 2005 to create the Summer School
      on Advanced Biotechnology, their aim was to exchange ideas and experience in a
      friendly and open-minded atmosphere to advance scientific knowledge. The network
      is a recipe for success: In 2017, it was the turn of the HES-SO Valais/Wallis to
      welcome the event to Sion from September 3 - 6.

PMID- 29179808
TI  - Ultrasound-Assisted Extraction of Anthocyanins from Red Rose Petals and New
      Spectrophotometric Methods for the Determination of Total Monomeric Anthocyanins.
AB  - In this study, four extraction technologies for the extraction of anthocyanins
      (Acyns) from red rose petals (RRPs) were investigated and compared, including
      ultrasound-assisted extraction (UAE), reflux extraction, Soxhlet extraction, and
      marinated extraction. UAE was the most suitable for the extraction of Acyns from
      RRPs because of its high extraction efficiency and short extraction time. The
      results showed that the best conditions for UAE are an extraction solution of
      ethanol-0.1 N HCl (80 + 20, v/v), a solid-to-liquid ratio of 1:40 g/mL, a
      temperature of 30 degrees C, and an extraction time of 15 min performed three
      times. Using such conditions, 320.4 mg Acyns/100 g RRPs was extracted. UAE was
      followed by two new difference spectrophotometric (DS) methods, which were
      developed for the fast and simple determination of Acyns in RRPs. Under the
      optimum experimental conditions, a linear response was observed for Acyns in the
      range of 12.5-62.5 MUg/mL for the two proposed methods, with correlation
      coefficients (r) ranging from 0.9988 to 0.9995. The mean recovery values of Acyns
      for the DS methods were in the range of 99.8-101.5%, and the RSD was 0.5%. The
      respective LOD and the LOQ values were 1.4 and 4.8 for DS1 and 1.1 and 3.6 MUg/mL
      for DS2. The stability of Acyns was also studied.

PMID- 29179809
TI  - Factors that affect general practice as a choice of medical speciality:
      implications for policy development.
AB  - Objective This article critically appraises the range of personal, professional
      and social factors that affect the choice of speciality across medical students,
      prevocational doctors, general practice registrars and general
      practitioners.Methods This qualitative study applied constructs from the fields
      of decision theory and career theory to better understand the complex nature of
      choosing a speciality. In all, 47 in-depth interviews were conducted with
      participants at different stages of their career cycle. The data was codified and
      analysed using NVivo to identify key factors that influenced speciality
      choice.Results The research identified 77 individual findings influencing general
      practice as a choice of medical speciality. These were distilled into a matrix to
      show that factors such as money, prestige and peer interaction did not have a
      compelling effect, whereas clinical and academic role models, flexibility, work
      life balance, scope of practice, connection with patients, training environment
      and practical opportunities did.Conclusion The findings indicate that the
      decision in relation to the choice of medical speciality is a complex cognitive
      process that is undertaken within a personal, social and professional context
      particular to each individual.What is known about the topic? Current literature
      aims to quantify changes in attitudes towards choice of speciality or the effect
      of particular variables in isolation while ignoring the complexity of this
      decision process and how the numerous variables compare with each other.What does
      this paper add? The present study is the first intergenerational research on this
      topic in the Australian context and the paper dismisses the role of prestige and
      remuneration as key drivers of choice in picking general practice as a
      speciality, noting that money is merely a 'hygiene factor'.What are the
      implications for policy makers? A policy framework outlining 10 key principles is
      presented to assist policy makers seeking to affect workforce outcomes by
      applying policy levers to influence doctors' choice of speciality.

PMID- 29179810
TI  - De novo transcription of thyroid hormone receptors is essential for early bovine
      embryo development in vitro.
AB  - Thyroid hormone receptor (THR) alpha and THRbeta mediate the genomic action of
      thyroid hormones (THs) that affect bovine embryo development. However, little is
      known about THRs in the preimplantation embryo. The aim of the present study was
      to investigate the importance of THRs in in vitro preimplantation bovine embryos.
      THR transcripts and protein levels were detected in developing preimplantation
      embryos up to the blastocyst stage. Embryonic transcription of THRs was inhibited
      by alpha-amanitin supplementation, and both maternal and embryonic transcription
      were knocked down by short interference (si) RNA microinjection. In the control
      group, mRNA and protein levels of THRs increased after fertilisation. In
      contrast, in both the transcription inhibition and knockdown groups there were
      significant (P<0.05) decreases in mRNA expression of THRs from the 2-cell stage
      onwards. However, protein levels of THRs were not altered at 2-cell stage,
      although they did exhibit a significant (P<0.05) decrease from the 4-cell stage.
      Moreover, inhibition of de novo transcripts of THRs using siRNA led to a
      significant (P<0.01) decrease in the developmental rate and cell number, as well
      as inducing a change in embryo morphology. In conclusion, THRs are transcribed
      soon after fertilisation, before major activation of the embryonic genome, and
      they are essential for bovine embryo development in vitro.

PMID- 29179811
TI  - Economic modelling of telehealth substitution of face-to-face specialist
      outpatient consultations for Queensland correctional facilities.
AB  - Objective The provision of healthcare services to inmates in correctional
      facilities is costly and resource-intensive. This study aimed to estimate the
      costs of transporting prisoners from 11 Queensland correctional facilities to the
      Princess Alexandra Hospital Secure Unit (PAHSU) in Brisbane for non-urgent
      specialist outpatient consultations and identify the cost consequences that would
      result from the substitution of face-to-face visits with telehealth
      consultations.Methods A 12-month retrospective review of patient activity at the
      PAHSU was conducted to obtain the number of transfers per correctional facility.
      The total cost of transfers was calculated with estimates for transport vehicle
      costs and correctional staff escort wages, per diem and accommodation costs. A
      cost model was developed to estimate the potential cost savings from substituting
      face-to-face consultations with telehealth consultations. A sensitivity analysis
      on the cost variables was conducted. Costs are reported from a government funding
      perspective and presented in 2016 Australian dollars (A$).Results There were 3539
      inmate appointments from July 2015 to June 2016 at the PAHSU, primarily for
      imaging, general practice, and orthopaedics. Telehealth may result in cost
      savings from negligible to A$969731, depending on the proportion, and travel
      distance, of face-to-face consultations substituted by telehealth. Wages of
      correctional staff were found to be the most sensitive variable.Conclusions Under
      the modelled conditions, telehealth may reduce the cost of providing specialist
      outpatient consultations to prisoners in Queensland correctional facilities.
      Telehealth may improve the timeliness of services to a traditionally underserved
      population.What is known about the topic? Specialist medical services are located
      in only a few metropolitan centres across Australia, which requires some
      populations to travel long distances to attend appointments. Some face-to-face
      specialist outpatient consultations can be substituted by telehealth.What does
      this paper add? Prisoners from correctional facilities represent one specific
      population that requires complex travel arrangements for specialist medical
      appointments. Transportation of prisoners for specialist health appointments
      represents a substantial cost to the government. This paper quantifies the annual
      cost in Queensland for transporting prisoners, taking into account fuel and
      vehicle costs, staff wages, per diem rates, and accommodation. In addition, it
      quantifies the costs of substituting face-to-face consultations with telehealth
      consultations.What are the implications for practitioners? This research
      encourages practitioners to consider using telehealth services for prisoners, as
      well providing an argument for tertiary centres to include telehealth as a model
      of care for this population. Telehealth can result in major cost savings and
      state and federal governments should consider implementation especially in
      Australia where correctional facilities and specialist services are separated by
      great geographic distances.

PMID- 29179812
TI  - Twists and turns.
AB  - Computational modelling of the heart tube during development reveals the
      interplay between tissue asymmetry and growth that helps our hearts take shape.

PMID- 29179816
TI  - World Mental Health Day.

PMID- 29179813
TI  - A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse
      heart looping dynamics.
AB  - How left-right patterning drives asymmetric morphogenesis is unclear. Here, we
      have quantified shape changes during mouse heart looping, from 3D reconstructions
      by HREM. In combination with cell labelling and computer simulations, we propose
      a novel model of heart looping. Buckling, when the cardiac tube grows between
      fixed poles, is modulated by the progressive breakdown of the dorsal mesocardium.
      We have identified sequential left-right asymmetries at the poles, which bias the
      buckling in opposite directions, thus leading to a helical shape. Our predictive
      model is useful to explore the parameter space generating shape variations. The
      role of the dorsal mesocardium was validated in Shh-/- mutants, which
      recapitulate heart shape changes expected from a persistent dorsal mesocardium.
      Our computer and quantitative tools provide novel insight into the mechanism of
      heart looping and the contribution of different factors, beyond the simple
      description of looping direction. This is relevant to congenital heart defects.

PMID- 29179814
TI  - The effect of perinatal brain injury on dopaminergic function and hippocampal
      volume in adult life.
AB  - Perinatal brain injuries, including hippocampal lesions, cause lasting changes in
      dopamine function in rodents, but it is not known if this occurs in humans. We
      compared adults who were born very preterm with perinatal brain injury to those
      born very preterm without perinatal brain injury, and age-matched controls born
      at full term using [18F]-DOPA PET and structural MRI. Dopamine synthesis capacity
      was reduced in the perinatal brain injury group relative to those without brain
      injury (Cohen's d = 1.36, p=0.02) and the control group (Cohen's d = 1.07,
      p=0.01). Hippocampal volume was reduced in the perinatal brain injury group
      relative to controls (Cohen's d = 1.17, p=0.01) and was positively correlated
      with striatal dopamine synthesis capacity (r = 0.344, p=0.03). This is the first
      evidence in humans linking neonatal hippocampal injury to adult dopamine
      dysfunction, and provides a potential mechanism linking early life risk factors
      to adult mental illness.

PMID- 29179817
TI  - A Concept Analysis of Substance Misuse to Inform Contemporary Terminology.
AB  - Previous diagnostic categories of substance abuse and dependence have given way
      to the current view that substance use disorders occur on a continuum with a
      broad range of severity. This current view is featured in the Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition (DSM V). In recognizing the
      role of stigma in preventing persons from seeking substance use treatment,
      advocates have called attention that particular terminology can fuel such stigma.
      To mitigate the negative effects of such stigmatizing language, the International
      Society of Addiction Journal Editors (ISAJE) recommends against using previously
      used and possibly pejorative terminology for substance abuse and dependence,
      unless a particular scientific justification exists. The purpose of this paper is
      to: (1) present a concept analysis of the term substance misuse and (2) recommend
      an alternate term for substance misuse that is neither pejorative nor
      inadvertently stigmatizing: at-risk substance use.

PMID- 29179815
TI  - CHARGE syndrome modeling using patient-iPSCs reveals defective migration of
      neural crest cells harboring CHD7 mutations.
AB  - CHARGE syndrome is caused by heterozygous mutations in the chromatin remodeler,
      CHD7, and is characterized by a set of malformations that, on clinical grounds,
      were historically postulated to arise from defects in neural crest formation
      during embryogenesis. To better delineate neural crest defects in CHARGE
      syndrome, we generated induced pluripotent stem cells (iPSCs) from two patients
      with typical syndrome manifestations, and characterized neural crest cells
      differentiated in vitro from these iPSCs (iPSC-NCCs). We found that expression of
      genes associated with cell migration was altered in CHARGE iPSC-NCCs compared to
      control iPSC-NCCs. Consistently, CHARGE iPSC-NCCs showed defective delamination,
      migration and motility in vitro, and their transplantation in ovo revealed
      overall defective migratory activity in the chick embryo. These results support
      the historical inference that CHARGE syndrome patients exhibit defects in neural
      crest migration, and provide the first successful application of patient-derived
      iPSCs in modeling craniofacial disorders.

PMID- 29179818
TI  - The Effect of the Cognitive-behavioral Model-based Psychoeducation and Exercise
      Intervention on Quality of Life in Alcohol Use Disorder.
AB  - PURPOSE: The aim of the study was to assess the effect of the cognitive behavior
      model (CBM)-based psychoeducation and exercise intervention on quality of life
      (QoL) in alcohol use disorder (AUD). DESIGN: This study was a non-randomized
      controlled trial. METHODS: CBM-based psychoeducation and exercise intervention
      was applied to the experimental group four times a week for 6weeks; no
      intervention was applied to the control group. FINDINGS: No difference was seen
      between the points of pretest QoL of the experimental and control groups
      (p>0.05). However, according to the posttest, the experimental group's mean score
      of QoL was higher than the control groups (p<0.05). CONCLUSION: It was found that
      CBM-based psychoeducation and exercise intervention applied to individuals with
      AUD affected the QoL positively. CLINICAL RELEVANCE: CBM-based psychoeducation
      and exercise intervention can be used by nurses to improve AUD individuals'
      quality of life.

PMID- 29179819
TI  - Predictive Factors of Anxiety and Depression in Patients with Acute Coronary
      Syndrome.
AB  - OBJECTIVE: To identify the predictive factors of anxiety and depression in
      patients with acute coronary syndrome. METHODS: Cross-sectional and retrospective
      study conducted with 120 patients hospitalized with acute coronary syndrome.
      Factors interfering with anxiety and depression were assessed. RESULTS: Anxiety
      was related to sex, stress, years of education, and depression, while depression
      was related to sex, diabetes mellitus, obesity, years of education, and trait
      anxiety. CONCLUSIONS: Obesity and anxiety were considered predictive factors for
      depression, while depression and fewer years of education were considered
      predictive factors for anxiety.

PMID- 29179820
TI  - Early Intervention in Psychosis: Health of the Nation Outcome Scales (HoNOS)
      Outcomes From a Five-Year Prospective Study.
AB  - INTRODUCTION: Over the last two decades, mental health services internationally
      have shifted towards intervening early in psychosis. The critical period for
      intervention is estimated to be five-years and many specialised programs target
      early psychosis. AIM/QUESTION: This prospective cohort study aimed to evaluate
      five-year outcomes from an early psychosis program (EPP) that adopted an
      integrated model, providing nursing and multidisciplinary community mental
      healthcare to clients aged 16-65years, beyond the typical age range of 16
      25years. METHOD: We examined one routine outcome measure, the Health of the
      Nation Outcome Scales (HoNOS) across episodes of care for clients receiving EPP
      over a 5year period (n=239), comparing these results with HoNOS outcomes in an
      Australian national dataset for all public mental health clients. RESULTS: HoNOS
      improvements were highly significant from intake to discharge and from review to
      discharge for EPP clients, and these compared well with national outcome
      performance. CONCLUSION: There is potential for mental health nurses and other
      clinicians to significantly improve client symptoms and functioning, in a model
      of early psychosis treatment beyond a youth focus.

PMID- 29179821
TI  - An Analysis of Stories From Those Who Have Encountered Catastrophic Loss From
      Flood.
AB  - Analyzing stories from those who have suffered catastrophic loss from flood may
      offer a means to better understand recovery of the survivors from their
      perspective. The purpose of this research was to examine the lived experience of
      those who faced catastrophic loss from flood. Stories were gathered from eight
      participants, who experienced catastrophic loss of home and possessions resultant
      of massive flooding. Following analysis, three "turning points" were identified
      within the story plot which included: Facing the devastation, Embracing the
      rebuilding, and Developing inner strength. Themes within the turning points were
      identified demonstrating transformational perspectives of self and world.

PMID- 29179822
TI  - Relationships of Mental Health and Internet Use in Korean Adolescents.
AB  - AIM: The purpose of this study was to identify the relationships of mental health
      and internet use in Korean adolescents. Also, it was intended to provide
      guidelines for reducing internet overuse based on the influencing factors of
      internet use. METHODS: Participants in this study were convenient sampling, and
      selected middle and high school students in Incheon metropolitan city, South
      Korea. Internet use and mental health of adolescents were measured by self
      reported instruments. This study was carried out from June to July 2014. 1248
      participants were collected overall except for insufficient data. The data were
      analyzed by descriptive statistics, t-test, ANOVA, Pearson's correlation
      coefficient, and multiple regression. RESULTS: There were significant
      correlations between mental health and internet use. The significant influencing
      factors of internet use were normal internet use group, mental health, middle
      school, internet using time on weekends (3h or more), internet using time at a
      time (3h or more), and high school record. These six variables accounted for
      38.1% of internet use. CONCLUSIONS: The results of this study will be used as
      guidelines for reducing internet overuse of adolescents.

PMID- 29179823
TI  - The Importance of Perceived Need in Help Seeking for Japanese Women: A
      Preliminary Investigation of Sociocultural Contributions.

PMID- 29179824
TI  - Eating Disorder Examination-Questionnaire (EDE-Q): Norms for Clinical Sample of
      Female Adolescents with Anorexia Nervosa.

PMID- 29179825
TI  - Psychometric Properties of the Essen Climate Evaluation Schema (EssenCES) in a
      Sample of General Psychiatric Wards.
AB  - OBJECTIVE: The questionnaire EssenCES (Essen Climate Evaluation Schema) is a
      widely used instrument to assess social climate in forensic psychiatric and
      correctional institutions. The purpose of this study was to evaluate the EssenCES
      in a general psychiatric setting, where it had not previously been evaluated.
      DESIGN: 648 staff members and 551 patients from 47 general psychiatric wards
      across 16 hospitals in Germany completed the EssenCES. Factor-, correlation- and
      scale-analyses were carried out to inspect the questionnaire's properties.
      RESULTS: The proposed three-dimensional factor structure of the instrument was
      confirmed. Results indicated that the EssenCES subscales Patients' Cohesion and
      Experienced Safety had high internal consistency, whereas elimination of item 16
      would improve the internal consistency of Therapeutic Hold. Correlations between
      the EssenCES subscales and other measures supported the validity of the
      questionnaire. CONCLUSION: The results suggest that the EssenCES is suitable for
      usage in general psychiatric settings. Along with its brevity, it seems useful as
      an economic and valid screening instrument for a ward's social climate. Reasons
      are given why item 16 should be retained.

PMID- 29179826
TI  - Individual Factors Affecting Self-esteem, and Relationships Among Self-esteem,
      Body Mass Index, and Body Image in Patients With Schizophrenia.
AB  - The purposes of this study were to identify correlations between body mass index,
      body image, and self-esteem in patients with schizophrenia and to analyse the
      specific factors affecting self-esteem. This study had a descriptive design,
      utilising a cross-sectional survey. Participants were patients with schizophrenia
      who were admitted to a mental health facility in South Korea. A total of 180
      questionnaires were distributed, and an appropriate total sample size of 167
      valid questionnaires was analysed. Self-esteem was significantly correlated with
      body image, the subscale of appearance orientation, and body areas satisfaction.
      However, body mass index exhibited no significant correlation with any variable.
      The variables found to have a significant explanatory power of 21.4% were
      appearance orientation and body areas satisfaction. The explanatory power of all
      factors was 33.6%. The self-esteem of patients with schizophrenia was influenced
      by body mass index and body image. The positive symptoms of schizophrenia can be
      controlled by medication, whereas negative symptoms can be improved through
      education and nursing care with medication. Thus, psychiatric nurses should
      develop education and care programs that contribute to the positive body image
      and self-esteem of patients with schizophrenia.

PMID- 29179827
TI  - Developing a Multiple Caregiver Group for Caregivers of Adolescents With
      Disruptive Behaviors.
AB  - This article describes the development of a 6-week multiple caregiver group
      intervention for primary caregivers of adolescents diagnosed with Oppositional
      Defiant Disorder or Conduct Disorder in low-income African American families. The
      intervention is aimed at increasing the primary caregivers' self-efficacy in
      managing interactions within the family and especially with child serving
      educational, mental health, juvenile justice, and child welfare systems.
      Development of the intervention involved seven iterative activities performed in
      a collaborative effort between an interdisciplinary academic team, community
      engagement specialists, members of the targeted population, and clinical partners
      from a large public mental health system. The intervention development process
      described in this article can provide guidance for teams that aim to develop new
      mental health interventions that target specific outcomes in populations with
      unique needs.

PMID- 29179828
TI  - Reducing the Risk of Cardiovascular Diseases in Non-selected Outpatients With
      Schizophrenia: A 30-Month Program Conducted in a Real-life Setting.
AB  - BACKGROUND: The most common cause of premature death in people with schizophrenia
      is cardiovascular disease, partially explained by an unhealthy lifestyle,
      smoking, poor diet and sedentary behavior. We aimed to reduce cardiovascular risk
      factors. METHOD: Naturalistic follow-up study with 54 long-term-treated non
      selected outpatients with schizophrenia. The 30-month program consisted of
      individual guidance, group sessions and normal treatment and care offered in our
      clinic. RESULTS: On average, the participating women reduced their waist
      circumference by 11.4cm (P=0.037), whereas the participating men increased their
      waist circumference by 3.3cm (P=0.590). Patients' consumption of fast food was
      reduced from 1.2 to 0.8 times/week (P=0.016), just as their consumption of soft
      drinks was reduced from 0.7 to 0.1l/day (P=0.006). Their consumption of coffee
      increased from 1.6 to 2.5 cups/day (P=0.086). The time women spent on light
      physical activity increased from 134 to 469min/week (P=0.055). The number of
      daily cigarettes smoked was reduced by 25.7% for all smokers. CONCLUSIONS: Our
      program showed that it is possible for women but not for men to reduce their risk
      factors for developing cardiovascular disease. The program is manageable in most
      outpatient clinics and can be performed by nursing staff interested in physical
      health with support from and in cooperation with medical doctors, psychiatrist
      and leaders/managers.

PMID- 29179829
TI  - The Impact of Mental Health Reform on Mental Illness Stigmas in Israel.
AB  - This study examined public perception of stigmas relating to mental illness six
      months after a reform, which integrated mental health care into primary care in
      Israel. The results reveal that the public feels uncomfortable seeking referral
      to mental health services through the public health system, with Arab Israelis
      and men expressing lower levels of comfort than did Jewish Israelis. The current
      reform has not solved the issue of public stigma regarding mental health care.
      The study suggests that the current reforms must be accompanied over time with
      appropriate public education regarding mental illness.

PMID- 29179830
TI  - Categorising Patients Mental Illness by Medical Surgical Nurses in the General
      Hospital Ward: A Focus Group Study.
AB  - AIM: To gain insight into medical surgical nurses' process(es) of categorising
      mental illness in general hospitals. BACKGROUND: Categorising patients is a daily
      social practice that helps medical surgical nurses understand their work and
      actions. Medical surgical nurses' categorising of mentally ill patients in
      general hospitals is a means in which they articulate their understanding of
      mental illness and perform their clinical practice. How medical surgical nurses
      categorise, and the impact that categorising can have on their work practices is
      poorly understood. DESIGN: A focus group study. METHOD: Focus group discussions
      (n=2) of medical surgical nurses' understanding and experience of delivering care
      to patients with mental illness in a general tertiary referral hospital were
      conducted in November 2014. Discourse analysis was used to analyse the
      transcribed data to uncover how participants made discursive evaluations and how
      this related to their daily clinical practice. RESULTS: The analysis uncovered
      participant's use of four categories of mentally ill patients: the managed, the
      unpredictable, the emotional and the dangerous. For participants these categories
      explained and justified their clinical practice as linked to the challenges and
      barriers they experienced in providing effective care within the larger
      healthcare organisation. CONCLUSION: The language used by medical/surgical
      reflects the wider discourse of managerialism in healthcare organisations. The
      recognition of these categories can be used by educators, liaison mental health
      services and policy makers to reconsider service design and learning
      opportunities for medical surgical nurses to reduce stigmatisation of patients
      with mental illness.

PMID- 29179832
TI  - Capturing the Interpersonal Process of Psychiatric Nurses: A Model for
      Engagement.
AB  - Staff members' engagement with patients is a critical element of inpatient
      psychiatric care, essential to safety, the hospitalization experience and the
      development of a culture of care. Currently broad concerns exist around the
      amount of time inpatient psychiatric nurses expend in patient engagement and the
      quality of these interactions. In this paper we present a model of engagement
      that clarifies necessary skills to support the engagement process. The model is
      based on Peplau's theory of interpersonal relations, patients' ideas on healing
      elements of psychiatric hospitalization and research on inpatient therapeutic
      relationships. We are currently using this model for a web-based
      teaching/learning course to cultivate interpersonal engagement, and to explicate
      how through operationalizing their inpatient role, nurses support patients in the
      development of their mental health and well-being.

PMID- 29179831
TI  - Improving metabolic monitoring rate for young people aged 35 and younger taking
      antipsychotic medications to treat a psychosis: A literature review.
AB  - Young people aged 35 and younger who are taking antipsychotic medications to
      treat a psychosis are a high risk for developing metabolic syndrome due to the
      adverse effects of the medications. This paper reports the finding of a review of
      literature to identify interventions to improve metabolic monitoring rates in
      this group. A review of 478 studies identified 15 articles which met the
      inclusion criteria. Five articles reported single-intervention studies and the
      remaining integrated two or more interventions to improve uptake level of
      metabolic monitoring. As metabolic syndrome can be detected early through
      metabolic monitoring in young people taking antipsychotics, early intervention is
      important to improve their physical health trajectory.

PMID- 29179833
TI  - Does Assertive Community Treatment Reduce the Use of Compulsory Admissions?
AB  - BACKGROUND: The growing number of compulsory admissions in Denmark and other
      countries is a compelling challenge. We hypothesized that Assertive Community
      Treatment (ACT) may have the quality to reduce the use of several type of
      coercion including compulsory admissions. Although ACT is not designed for
      coercion prevention, it may prove efficient in averting major crisis among the
      included patients. Studies in Denmark showed that ACT has a major and significant
      advantage in reducing number and length of admissions. METHODS/DESIGN: We
      collected service data from National Case Register at three psychiatric
      hospitals, which constitutes the inpatient and outpatient mental health services
      in the North Denmark Region. Data included psychiatric and somatic service use
      among 240 patients starting in ACT. Primary measure concerned the extent to which
      ACT might reduce compulsory admissions. RESULTS: During a five years period
      patients allocated to ACT show decreasing admission trends. In comparison with
      all other psychiatric service users, we found a significant difference in trends
      concerning voluntary admissions and involuntary admissions according to the
      dangerous criterion, and decrease in number of contacts to Psychiatric Emergency
      Room (PER) CONCLUSION: An assertive approach undoubtedly reduces hospitalization
      including some involuntary admissions. ACT is preferable from both team and
      patient perspectives, and further caused reduction of PER visits compared to
      standard treatment. PERSPECTIVES: The criterion of Severe Mental Illness (SMI)
      may be revised to facilitate ACT to be offered to a larger group of SMI patients.
      In addition, introduction of Crisis Intervention Teams should be considered and
      allocated to PER.

PMID- 29179836
TI  - Introduction.

PMID- 29179834
TI  - Chronic Sorrow in the Elderly.

PMID- 29179837
TI  - ?

PMID- 29179838
TI  - ?

PMID- 29179839
TI  - [Frailty and ageing, concept and definitions].
AB  - Increased life expectancy, ageing and the accumulation of chronic pathologies
      leads to a certain functional dependence. The term 'frailty' is used to refer to
      the state of 'predependence' in elderly people. It is therefore important to
      detect and prevent frailty and provide frail elderly people with the adapted
      care. Training caregivers to recognise signs of frailty is essential.

PMID- 29179840
TI  - [Collaboration in the prevention of frailty].
AB  - Hospitalisation is an opportunity for frailty in the elderly to be detected. The
      collaboration of the assessment and prevention geriatrician-nurse partnership,
      combined with the skills of the advanced practice nurse in gerontology, helps to
      instil a culture of frailty prevention in the teams and create adapted care
      pathways.

PMID- 29179841
TI  - [Frailty of elderly people with diabetes].
AB  - The frailty of elderly people with diabetes requires various factors to be taken
      into account including lifestyle, the moment of the diagnosis, the patient's
      experience, the social context including any financial difficulties. It is
      thereby apparent that the support requirements differ depending on the
      situations. Medical telemonitoring can be an appropriate solution.

PMID- 29179842
TI  - [Nutritional management of elderly people, everyone's concern].
AB  - In order to provide the appropriate care with regard to nutrition and the fight
      against frailty, it is important to know how to analyse the physical and
      physiological capacities of the ageing population. These are assessed in relation
      to the measurement of the patient's muscle strength, walking speed and balance.

PMID- 29179843
TI  - ["The path towards frailty must be broken"].
AB  - Cecile Richaud is a physiotherapist at Grenoble. A senior health manager in
      rehabilitation, rehabilitation coordinator and member of the nursing leadership
      team, she explains the benefit of the detection, prevention and management of
      frailty and education in the elderly.

PMID- 29179844
TI  - [Innovation, digital application and nursing leadership].
AB  - The private practice nurse has her own particular holistic vision for helping
      patients to remain living in their home. With entry to the profession now
      requiring university level studies, advanced practice is based on the clinical
      aspect, the reflexive approach and the leadership necessary to initiate
      innovative projects aimed at improving the quality of the care provided by
      removing the barriers between the different players for the benefit notably of
      elderly people.

PMID- 29179845
TI  - [Wellbeing, team spirit and a fun run for women].
AB  - The fun run La Parisienne, has been bringing together in Paris every September
      for the last 21 years, thousands of women running alongside each other to say no
      to breast cancer. Many caregivers also take part, in teams or with friends, like
      at the Odyssea fun run in which families can also participate. Charity sports
      events for the benefit of research which promote femininity, team spirit, sharing
      and wellbeing.

PMID- 29179846
TI  - [Supporting people with Diogenes syndrome].
AB  - Diogenes syndrome is a chronic condition often affecting elderly people,
      especially those living in isolation. It is characterised by self-neglect and
      compulsive hoarding. Medico-social professionals working with people in their
      home, have reflected on levers to help improve the complex support of these
      patients.

PMID- 29179847
TI  - [Sophrology for developing strategies to help patients adapt to cancer
      treatments].
AB  - Radiotherapy forms a significant part of cancer treatment. Caregivers support and
      advise patients to help them to adapt to the treatment and limit the occurrence
      of side effects. A nurse and member of a mobile support care and palliative care
      unit shares her experience of working in a team using sophrology to relieve the
      anxiety resulting from the wearing of a mask in radiotherapy.

PMID- 29179848
TI  - [Treatment of incontinence associated dermatitis].
AB  - Incontinence associated dermatitis is one of the main complications of
      incontinence. Very painful, it is a well-known risk factor of pressure ulcers.
      Nurse assistants and nurses are on the frontline for detecting and treating the
      condition.

PMID- 29179849
TI  - ?

PMID- 29179850
TI  - A nurse-led review of a child with asthma.
AB  - Eliza is a practice nurse working in a large general practice in England. She is
      a trained nurse with additional qualifications in chronic disease management, and
      is also a registered prescriber. This means she can initiate or repeat medical
      prescriptions. Today Eliza is reviewing her asthma patients.

PMID- 29179851
TI  - ?

PMID- 29179852
TI  - ?

PMID- 29179853
TI  - ?

PMID- 29179854
TI  - ?

PMID- 29179855
TI  - Analysis of the influence of the T393C polymorphism of the GNAS gene on the
      clinical expression of primary hyperparathyroidism.
AB  - BACKGROUND: The receptor of parathyroid hormone and parathyroid hormone-related
      protein (PTH/PTHrp) is located in the cell membrane of target tissues - kidney
      and osteoblasts. It is a G protein-coupled-receptor whose Gsalpha subunit is
      encoded by the GNAS gene. Our aim was to study whether the single nucleotide
      polymorphism (SNP) T393C of the GNAS gene is associated with renal stones, bone
      mineral density (BMD), or bone remodelling markers in primary hyperparathyroidism
      (PHPT). METHODS: An analysis was made of clinical and biochemical parameters and
      densitometric values in three areas and their relationship with the T393C SNP of
      the GNAS gene in 261 patients with primary hyperparathyroidism and in 328 healthy
      controls. Genotyping was performed using the Custom Taqman(r) SNP Genotyping
      assay. RESULTS: The genotype frequencies of GNAS T/C 393 were similar in the
      control and PHPT groups. No association was found between genotypes and clinical
      expression of PHPT (renal stones and bone fractures). A nonstatistically
      significant trend was seen to lower BMD in the lumbar spine, femoral neck, and
      total hip in both PHPT and control C homozygote subjects. CONCLUSION: Genetic
      susceptibility to PHPT related to the GNAS T393C polymorphism or a major
      influence in its development and clinical expression were found. A C allele
      related susceptibility to lower BMD in trabecular bone in both PHPT and control
      subjects is not sufficient to suggest a more severe clinical expression of PHPT.
      This trend may be considered as a basis for further studies with larger sample
      sizes and complementary functional evaluation.

PMID- 29179856
TI  - Learning curve of thyroid fine-needle aspiration biopsy.
AB  - BACKGROUND: Fine-needle aspiration biopsy (FNAB) is the reference procedure for
      thyroid nodule evaluation. Its main limitation are inadequate samples, which
      should be less than 20%. OBJECTIVE: To analyze the learning curve of the
      procedure by comparing the results of a non-experienced endocrinologist
      (endocrinologist 2) to those of an experienced one (endocrinologist 1). MATERIAL
      AND METHODS: Sixty FNABs were analyzed from February to June 2016. Each
      endocrinologist made 2punctures of every nodule in a random order. This order and
      the professional making every puncture were unknown to the pathologist who
      examined the samples. RESULTS: Endocrinologist 1 had a higher percentage of
      diagnoses than endocrinologist 2 (82% vs. 72%, P=.015). In the first 20 FNABs,
      the difference between both physicians was remarkable and statistically
      significant (80% vs. 50%, P=.047). In the following 20 FNABs, the difference
      narrowed and was not statistically significant (90% vs. 65%, P=.058). In the
      final 20 FNABs, the difference was minimal and not statistically significant (75%
      vs. 70%, P=.723). CONCLUSIONS: The learning curve of ultrasound-guided FNAB may
      be completed in a suitable environment by performing it at least 60 times.
      Although the guidelines recommend at least 3punctures per nodule, 2are enough to
      achieve an accurate percentage of diagnoses.

PMID- 29179857
TI  - Transition from intravenous insulin to subcutaneous long-acting insulin in
      critical care patients on enteral or parenteral nutrition.
AB  - BACKGROUND AND AIMS: The optimal initial dose of subcutaneous (SC) insulin after
      intravenous (IV) infusion is controversial, especially in patients receiving
      continuous enteral nutrition (EN) or total parenteral nutrition (TPN). The aim of
      this study was to evaluate the strategy used at our hospital intensive care unit
      (ICU) in patients switched from IV insulin to SC insulin glargine while receiving
      EN or TPN. DESIGN AND METHODS: A retrospective analysis was made of 27 patients
      on EN and 14 on TPN switched from IV infusion insulin to SC insulin. The initial
      dose of SC insulin was estimated as 50% of the daily IV insulin requirements,
      extrapolated from the previous 12h. A corrective dose of short-acting insulin
      (lispro) was used when necessary. RESULTS: Mean blood glucose (BG) level during
      SC insulin treatment was 136+/-35mg/dL in the EN group and 157+/-37mg/dL in the
      TPN group (p=0.01). In the TPN group, mean BG was >180mg/dL during the first
      three days after switching, and a 41% increase in the glargine dose was required
      to achieve the target BG. In the EN group, mean BG remained <180mg/dL throughout
      the days of transition and the dose of glargine remained unchanged. CONCLUSIONS:
      In the transition from IV to SC insulin therapy, initial insulin glargine dose
      estimated as 50% of daily IV insulin requirements is adequate for patients on EN,
      but inadequate in those given TPN.

PMID- 29179858
TI  - Reply to the comment to our article titled: "Association of metabolic syndrome
      with low birth weight of birth, intake hypercaloric diets and acanthosis
      nigricans in childhood and teens with overweight and obesity".

PMID- 29179859
TI  - Erratum to "Bariatric surgery results in patients with type 1 diabetes mellitus
      on continuous subcutaneous insulin infusion therapy".

PMID- 29179860
TI  - Pseudophakic Macular Edema in Primary Open-Angle Glaucoma: A Prospective Study
      Using Spectral-Domain Optical Coherence Tomography.

PMID- 29179861
TI  - Assessment of Optical Coherence Tomography Color Probability Codes in Myopic
      Glaucoma Eyes After Applying a Myopic Normative Database.

PMID- 29179862
TI  - Time to change perspectives on HPV in oropharyngeal cancer. A systematic review
      of HPV prevalence per oropharyngeal sub-site the last 3 years.
AB  - OBJECTIVES: Human papillomavirus (HPV) as a risk factor in oropharyngeal squamous
      cell carcinoma (OPSCC) is well established. However, accumulating data imply that
      the OPSCC concept is too unspecific with regard to HPV prevalence and clinical
      importance. To further study the role of HPV in OPSCC by sub-site, a systematic
      review and meta-analysis was performed. MATERIAL AND METHOD: PubMed was searched
      and all studies reporting HPV data (p16/HPV DNA/RNA) in both "lymphoepithelial
      associated" (i.e. tonsillar and base of tongue cancer; TSCC and BOTSCC
      respectively) and "non-lymphoepithelial" ("other" OPSCC) OPSCC were included.
      Pooled odds ratios by HPV detection method were analysed using a random effects
      model. RESULTS: In total, 58 unique patient cohorts were identified. Total HPV
      prevalence in TSCC/BOTSCC was 56%, 95%CI: 55-57% (59%, 95%CI: 58-60% for TSCC
      only) as compared to 19%, 95%CI: 17-20%, in "other" OPSCC. Significant
      association of HPV to TSCC/BOTSCC vs. "other" OPSCC was observed no matter HPV
      detection method used, but statistical homogeneity was only observed when studies
      using algorithm based HPV detection were pooled. CONCLUSION: HPV prevalence
      differs markedly between OPSCC sub-sites and while the role of HPV in TSCC/BOTSCC
      is strong, the role in "other" OPSCC is more uncertain and needs further
      evaluation.

PMID- 29179863
TI  - Comparative study of a novel application of automated HR HPV assay and stability
      in a previously untested Preservative media.
AB  - BACKGROUND: The suitability and stability of cervical cells in Novaprep media
      (NHQ) for certain HPV assays is unknown. METHODS: We evaluated the accuracy of an
      automated HPV assay (Abbott RealTime HR HPV) for cervical cells prepared in NHQ
      and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the
      assay manufacturers media; repeatability and reproducibility of HPV results and
      the stability of detectable HPV in NHQ over time compared to CE marked liquid
      based cytology preservatives. Cell lines were used to simulate patient samples.
      RESULTS: Cells stored in NHQ produced accurate, repeatable and reproducible
      results. Stability in NHQ was comparable to the best performing LBC, with at
      least 7 months' stability at 18-25 degrees C, 2-8 degrees C, -20 degrees C and 
      80 degrees C; and at least 3 months' stability at 40 degrees C. Similar results
      were obtained for pre-treated NHQ except only 3.5 months' stability at 18-25
      degrees C. Cell line samples in all media and concentrations tested were detected
      appropriately by the assay. CONCLUSIONS: Based on this first stage validation
      analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV
      assay. There should be no reservations for inclusion of NHQ in any further
      validation and clinical performance evaluation of this assay.

PMID- 29179864
TI  - Acceptability of cervical cancer screening using visual inspection among women
      attending a childhood immunization clinic in Uganda.
AB  - OBJECTIVE: To evaluate the acceptability and performance of cervical cancer (CC)
      screening using visual inspection with acetic acid (VIA) integrated into a rural
      immunization clinic in Uganda. METHODS/MATERIALS: We conducted a cross-sectional
      pilot study in rural Uganda. We explored associations between women's
      characteristics and acceptance of VIA testing. We collected samples for
      Papanicolaou (Pap) smear testing in a random subset of women and used results
      from this test as a comparator for assessing VIA performance. RESULTS: We
      enrolled 625 women of whom 571 (91.4%) accepted and 54 (8.6%) refused CC
      screening. In the univariate model, age (Odds Ratio (OR)=1.10; p-value<0.001) and
      employment status (OR 2.00; p-value=0.019) were significantly associated with
      acceptance of VIA screening. In the multivariate model, no characteristic was
      independently associated with acceptance of VIA screening after adjusting for
      other factors. Compared to reference Pap smear, CC screening with VIA had a
      sensitivity of 50% and a specificity of 97.7%. CONCLUSIONS: CC screening with VIA
      is highly acceptable in the setting of rural immunization clinics in Uganda.
      Studies to assess which screening method would be the most effective and cost
      effective are needed before stakeholders can consider adopting screening programs
      at scale.

PMID- 29179865
TI  - What works for human papillomavirus vaccine introduction in low and middle-income
      countries?
AB  - Since 2007, low and middle-income countries (LMICs) have gained experience
      delivering HPV vaccines through HPV vaccination pilots, demonstration projects
      and national programmes. This commentary summarises lessons from HPV vaccination
      experiences in 45 LMICs and what works for HPV vaccination introduction. Methods
      included a systematic literature review, unpublished document review, and key
      informant interviews. Data were extracted from 61 peer-reviewed articles, 11
      conference abstracts, 188 technical reports, and 56 interviews, with quantitative
      data analysed descriptively and qualitative data analysed thematically. Key
      lessons are described under five themes of preparation, communications, delivery,
      coverage achievements, and sustainability. Lessons learnt were generally
      consistent across countries and projects and sufficient lessons have been learnt
      for countries to deliver HPV vaccine through phased national rollout rather than
      demonstration projects. However, challenges remain in securing the political will
      and financial resources necessary to implement successful national programmes.

PMID- 29179866
TI  - miRNA-expression in tonsillar squamous cell carcinomas in relation to HPV
      infection and expression of the antileukoproteinase SLPI.
AB  - The aim of this study was to determine if micro-(mi-)RNAs are involved in the
      previously reported inverse correlation between the antileukoproteinase SLPI,
      HPV, and smoking habit of head and neck squamous cells carcinoma (HNSCC)
      patients. HPV-status and SLPI-protein expression were determined in tonsillar SCC
      (TSCC; n=126). Differentially expressed miRNAs dependent on HPV-status and SLPI
      expression were detected by microarray; possible binding-sites in SLPI- and HPVE6
      mRNAs were determined in silico. Survival rates were estimated testing prognostic
      values of HPV-status, SLPI- and miRNA-expression. miRNA-array identified 24 up
      regulated and 10 down-regulated miRNAs in HPV-positive versus HPV-negative TSCC
      (p<0.01; HPV-positivity: 42.1%). HPV-positivity resulted in two up-regulated
      miRNAs in SLPI-positive TSCC. Of 16 further miRNAs, eight miRNAs were up- and
      eight were down-regulated in SLPI-negative TSCC. RT-q-PCR-validation of the four
      most differentially expressed miRNAs showed that miR-363 is expressed strongest
      in SLPI-negative/HPV-positive TSSC. In silico-analysis of all differentially
      expressed miRNAs identified miR-363, miR-210, miR-130a, and miR-181a with
      possible binding sites in the HPV16-E6-mRNA, but none were predicted in the SLPI
      mRNA. HPV-positivity, low SLPI-levels and high miR-363-levels are significantly
      associated with better survival rates. The data presented here show that miR-363
      is associated with HPV-positive/SPLI-negative TSCC. The prognostic value of miR
      363 suggests a role in the assumed inverse correlation of smoking and SPLI
      expression in the mode of HPV-infections in tonsillar but possibly also other
      HNSCC.

PMID- 29179867
TI  - HPV vaccination of immunocompromised hosts.
AB  - It is well-established that immunocompromised people are at increased risk of HPV
      related disease compared with those who are immunocompetent. Prophylactic HPV sub
      unit vaccines are safe and immunogenic in immunocompromised people and it is
      strongly recommended that vaccination occur according to national guidelines.
      When delivered to immunocompromised populations, HPV vaccines should be given as
      a 3-dose regimen.

PMID- 29179869
TI  - Overcoming barriers in HPV vaccination and screening programs.
AB  - The Human Papillomavirus Prevention and Control Board brought together experts to
      discuss optimizing HPV vaccination and screening programs. Board members reviewed
      the safety profile of licensed HPV vaccines based on clinical and post-marketing
      data, reaching a consensus that current safety data is reassuring. Successful
      vaccination programs used well-coordinated communication campaigns, integrating
      (social) media to spread awareness. Communication of evidence supporting vaccine
      effectiveness had beneficial effects on the perception of the vaccine. However,
      anti-vaccination campaigns have threatened existing programs in many countries.
      Measurement and monitoring of HPV vaccine confidence over time could help
      understand the nature and scale of waning confidence, define issues and intervene
      appropriately using context-specific evidence-based strategies. Finally, a broad
      group of stakeholders, such as teachers, health care providers and the media
      should also be provided with accurate information and training to help support
      prevention efforts through enhanced understanding of the risks and benefits of
      vaccination. Similarly, while cervical cancer screening through population-based
      programs is highly effective, barriers to screening exist: awareness in countries
      with population-based screening programs, access for vulnerable populations, and
      access and affordability in low- and middle-income countries. Integration of
      primary and secondary prevention has the potential to accelerate the decrease in
      cervical cancer incidence.

PMID- 29179868
TI  - Prevalence and correlates of cervical HPV infection in a clinic-based sample of
      HIV-positive Hispanic women.
AB  - OBJECTIVES: Puerto Rico (PR), is the fifth highest jurisdiction of the United
      States of America (US) with respect to HIV prevalence and the leading in cervical
      cancer incidence. This cross-sectional study describes the prevalence and
      correlates of cervical HPV infection among a clinic-based sample of 302 women
      living with HIV/AIDS in PR. METHODS: Data collection included questionnaires,
      blood and cervical samples. Multivariable logistic regression models were used to
      estimate the magnitude of association (adjusted Prevalence odds ratio [aPOR])
      between HPV cervical infection and other covariates. RESULTS: Mean age of
      participants was 40.3 years (+/- 10.3SD). The prevalence of HPV infection was
      50.3%; 41.1% for low-risk types and 29.5% for high-risk types. Having >= 10
      lifetime sexual partners (aPOR = 2.10, 95% CI:1.02-4.29), an abnormal Pap (aPOR =
      3.58, 95% CI:1.93-6.62), active genital warts (aPOR = 3.45, 95% CI:1.60-7.42),
      and CD4 counts <= 200 (aPOR = 4.24, 95% CI: 1.67-10.78) were positively
      associated with any cervical HPV infection. Similar results were observed for HR
      HPV infection. CONCLUSIONS: A high burden of HPV co-infection exists among women
      living with HIV/AIDS in this population. Given the high incidence of HIV in PR
      and the higher risk of cervical cancer among women living with HIV/AIDS, HPV
      vaccination should be promoted in this population.

PMID- 29179870
TI  - Cutaneous HPV and alpha-mucosal 9-valent HPV sero-status associations.
AB  - Seroepidemiology of human papillomaviruses (HPV) among men is poorly understood.
      We examined the association between seropositivity to cutaneous HPV and 9-valent
      HPV (9vHPV) types. Six hundred men were randomly selected from the HPV Infection
      in Men (HIM) Study. Archived serum specimens were tested for antibodies against
      9vHPV types [low-risk (6/11) and high-risk (16/18/31/33/45/52/58)], and 14
      cutaneous types, including beta-types 5/8/12/14/17/22/23/24/38/47, alpha-type-27,
      gamma-type-4, u-type-1, and nu-type-41, using a GST L1-based multiplex serology
      assay. Risk factor data were collected through questionnaires. Logistic
      regression was used to evaluate associations between mucosal and cutaneous HPV
      types. Approximately 21% of men were positive for >= 1 cutaneous HPV type, and >=
      1 nine-valent HPV vaccine type at the same time. Men who were seropositive for
      any-cutaneous HPV were nearly twice as likely to be seropositive for 9vHPV
      (adjusted odds ratio (AOR) = 1.97, 95% confidence interval (CI): 1.30-2.99), high
      risk (AOR = 1.83; 95% CI: 1.04-3.20), low-risk (AOR = 1.92; 95% CI: 1.16-3.18),
      and four-valent, 4vHPV, (AOR = 2.01; 95% CI: 1.25-3.21). Type-specific cutaneous
      HPV seropositivity (types: 8/14/17/23/38/27/4/1) was also positively associated
      with seropositivity to 9vHPV, high-risk, and low-risk categories. These data
      indicate that exposure to cutaneous HPV and 9vHPV types is common. Future
      longitudinal studies are needed to assess the temporality of these associations.

PMID- 29179872
TI  - Improving skills and institutional capacity to strengthen adolescent immunisation
      programmes and health systems in African countries through HPV vaccine
      introduction.
AB  - Several African countries have recently introduced or are currently introducing
      the HPV vaccine, either nationwide or through demonstration projects, while some
      countries are planning for introduction. A collaborative project was developed to
      strengthen country adolescent immunisation programmes and health systems in the
      African Region, addressing unique public health considerations of HPV
      vaccination: adolescents as the primary target group, delivery platforms (e.g.
      school-based and facility based), socio-behavioural issues, and the opportunity
      to deliver other health interventions alongside HPV vaccination. Following a
      successful "taking-stock" meeting, a training programme was drafted to assist
      countries to strengthen the integration of adolescent health interventions using
      HPV vaccination as an entry point. Two workshops were conducted in the Eastern
      and Southern African Regions. All countries reported on progress made during a
      final joint symposium. Of the 20 countries invited to participate in either of
      the workshops and/or final symposium, 17 countries participated: Angola,
      Botswana, Ethiopia, Kenya, Malawi, Mauritius, Mozambique, Namibia, Rwanda,
      Seychelles, South Africa, South Sudan, Swaziland, Tanzania, Uganda, Zambia and
      Zimbabwe. Countries that are currently implementing HPV vaccination programmes,
      either nationally or through demonstration projects, reported varying degrees of
      integration with other adolescent health interventions. The most commonly
      reported adolescent health interventions alongside HPV vaccination include health
      education (including sexually transmitted infections), deworming and delivering
      of other vaccines like tetanus toxoid (TT) or tetanus diphtheria (Td). The
      project has successfully (a) established an African-based network that will
      advocate for incorporating the HPV vaccine into national immunisation programmes;
      (b) created a platform for experience exchange and thereby contributed to novel
      ideas of revitalising and strengthening school-based health programmes as
      delivery platform of adolescent immunisation services and other adolescent health
      interventions, as well as identifying ways of reaching out-of-school girls
      through facility and community based programmes; and (c) laid a foundation for
      incorporating future adolescent vaccination programmes.

PMID- 29179871
TI  - Modulation of antigen presenting cell functions during chronic HPV infection.
AB  - High-risk human papillomaviruses (HR-HPV) infect basal keratinocytes, where in
      some individuals they evade host immune responses and persist. Persistent HR-HPV
      infection of the cervix causes precancerous neoplasia that can eventuate in
      cervical cancer. Dendritic cells (DCs) are efficient in priming/cross-priming
      antigen-specific T cells and generating antiviral and antitumor cytotoxic CD8+ T
      cells. However, HR-HPV have adopted various immunosuppressive strategies, with
      modulation of DC function crucial to escape from the host adaptive immune
      response. HPV E6 and E7 oncoproteins alter recruitment and localization of
      epidermal DCs, while soluble regulatory factors derived from HPV-induced
      hyperplastic epithelium change DC development and influence initiation of
      specific cellular immune responses. This review focuses on current evidence for
      HR-HPV manipulation of antigen presentation in dendritic cells and escape from
      host immunity.

PMID- 29179873
TI  - Human papillomavirus (HPV) vaccine coverage achievements in low and middle-income
      countries 2007-2016.
AB  - INTRODUCTION: Since 2007, HPV vaccine has been available to low and middle income
      countries (LAMIC) for small-scale 'demonstration projects', or national
      programmes. We analysed coverage achieved in HPV vaccine demonstration projects
      and national programmes that had completed at least 6 months of implementation
      between January 2007-2016. METHODS: A mapping exercise identified 45 LAMICs with
      HPV vaccine delivery experience. Estimates of coverage and factors influencing
      coverage were obtained from 56 key informant interviews, a systematic published
      literature search of 5 databases that identified 61 relevant full texts and 188
      solicited unpublished documents, including coverage surveys. Coverage
      achievements were analysed descriptively against country or project/programme
      characteristics. Heterogeneity in data, funder requirements, and
      project/programme design precluded multivariate analysis. RESULTS: Estimates of
      uptake, schedule completion rates and/or final dose coverage were available from
      41 of 45 LAMICs included in the study. Only 17 estimates from 13 countries were
      from coverage surveys, most were administrative data. Final dose coverage
      estimates were all over 50% with most between 70% and 90%, and showed no trend
      over time. The majority of delivery strategies included schools as a vaccination
      venue. In countries with school enrolment rates below 90%, inclusion of
      strategies to reach out-of-school girls contributed to obtaining high coverage
      compared to school-only strategies. There was no correlation between final dose
      coverage and estimated recurrent financial costs of delivery from cost analyses.
      Coverage achieved during joint delivery of HPV vaccine combined with another
      intervention was variable with little/no evaluation of the correlates of success.
      CONCLUSIONS: This is the most comprehensive descriptive analysis of HPV vaccine
      coverage in LAMICs to date. It is possible to deliver HPV vaccine with excellent
      coverage in LAMICs. Further good quality data are needed from health facility
      based delivery strategies and national programmes to aid policymakers to
      effectively and sustainably scale-up HPV vaccination.

PMID- 29179874
TI  - HPV genotype-specific concordance between EuroArray HPV, Anyplex II HPV28 and
      Linear Array HPV Genotyping test in Australian cervical samples.
AB  - PURPOSE: To compare human papillomavirus genotype-specific performance of two
      genotyping assays, Anyplex II HPV28 (Seegene) and EuroArray HPV (EuroImmun), with
      Linear Array HPV (Roche). METHODS: DNA extracted from clinican-collected cervical
      brush specimens in PreservCyt medium (Hologic), from 403 women undergoing
      management for detected cytological abnormalities, was tested on the three
      assays. Genotype-specific agreement were assessed by Cohen's kappa statistic and
      Fisher's z-test of significance between proportions. RESULTS: Agreement between
      Linear Array and the other 2 assays was substantial to almost perfect (kappa =
      0.60 - 1.00) for most genotypes, and was almost perfect (kappa = 0.81 - 0.98) for
      almost all high-risk genotypes. Linear Array overall detected most genotypes more
      frequently, however this was only statistically significant for HPV51 (EuroArray;
      p = 0.0497), HPV52 (Anyplex II; p = 0.039) and HPV61 (Anyplex II; p=0.047).
      EuroArray detected signficantly more HPV26 (p = 0.002) and Anyplex II detected
      more HPV42 (p = 0.035) than Linear Array. Each assay performed differently for
      HPV68 detection: EuroArray and LA were in moderate to substantial agreement with
      Anyplex II (kappa = 0.46 and 0.62, respectively), but were in poor disagreement
      with each other (kappa = -0.01). CONCLUSIONS: EuroArray and Anyplex II had
      similar sensitivity to Linear Array for most high-risk genotypes, with slightly
      lower sensitivity for HPV 51 or 52.

PMID- 29179875
TI  - Surgical staging identified false HPV-negative cases in a large series of
      invasive cervical cancers.
AB  - OBJECTIVE: We examined a large series of biopsy-proven invasive cervical cancers
      with surgical staging and HPV re-testing to estimate the relevance of HPV
      negative cervical cancers in a Caucasian population. METHODS: We prospectively
      collected smears from 371 patients with a biopsy-proven diagnosis of cervical
      cancer for HC2 testing of high-risk HPV (HR-HPV). In HC2-negative cases, smears
      and paraffin embedded tissue blocks underwent additional HPV genotyping. RESULTS:
      HC2 tests showed 31/371 cases (8.8%) had negative findings. Surgical staging
      showed that 21/31 HC2-negative cases (68%) were not cervical cancer. Overall,
      340/350 cases of primary cervical cancer confirmed by surgical staging tested HC2
      positive (97.2%). Non-high-risk HPV subtypes were detected in five cases (one HPV
      53, one HPV-70, and three HPV-73) and high-risk subtypes in four patients with
      HC2-negative cervical cancer (two HPV 16 and two HPV-18). The remaining case, a
      primary undifferentiated carcinoma of the uterine cervix, tested negative for HPV
      DNA with all tests. CONCLUSIONS: The main explanation for HPV-negative cervical
      cancer was a false diagnosis, followed by cancers associated with non-HR-HPV
      types, and false-negative HR-HPV results. Truly HPV negative seem to be very rare
      in Caucasian populations. Retrospective analyses without surgical staging may
      overestimate the proportion of HPV negative cervical cancers.

PMID- 29179876
TI  - Syndemic synergy of HPV and other sexually transmitted pathogens in the
      development of high-grade anal squamous intraepithelial lesions.
AB  - BACKGROUND: Anal intraepithelial neoplasia is associated with high-risk human
      papillomavirus (hrHPV) as a precursor to anal cancer. However, factors other than
      hrHPV are likely to be involved and further study of cofactors is required
      because of the possibility of syndemic interactions. METHODS: Three hundred and
      fourteen patients underwent 457 operations. Histopathology and hrHPV testing
      using the Digene Hybrid Capture 2 (HC 2) method were performed. Demographic
      factors and sexually transmissible infections (STIs) were recorded. RESULTS:
      Results showed that hrHPV alone was associated with HSIL (OR = 4.65, p < 0.001).
      None of the other STIs were alone associated with HSIL but amplification of risk
      was found when hrHPV infection occurred with HIV (OR = 11.1); syphilis (OR =
      5.58); HSV 2 (OR = 7.85); gonorrhoea (OR = 6.45) and some other infections.
      CONCLUSIONS: These results suggest that hrHPV is a sufficient cause of anal HSIL.
      Seropositivity for HIV, HSV 2, T. pallidum, HBV and HCV and a history of
      gonorrhoea or chlamydia exert a powerful amplifying factor increasing the risk of
      HSIL above the risk with hrHPV alone. Other co-factors which are associated with
      an increased risk of HSIL are increased age, male gender, MSM behaviour and self
      reported history of more than 50 sexual partners. This pattern of disease in
      patients with warts is characteristic of a syndemic with potential serious
      increased risk of anal carcinoma.

PMID- 29179877
TI  - Psychosocial correlates of HPV vaccine acceptability in college males: A cross
      sectional exploratory study.
AB  - BACKGROUND: Most college males are not immunized against the human papillomavirus
      (HPV) and are at high risk of HPV infection. Most research of correlates of HPV
      vaccine acceptability in college males has assessed vaccine acceptability as a
      binary outcome, e.g., vaccinated or not vaccinated, without considering that some
      students may not even be aware that the HPV vaccine can be given to males. Our
      objective was to evaluate the psychosocial correlates of HPV acceptability in
      college males, based on multiple stages of HPV decision-making. METHODS: We used
      an online questionnaire to collect data from college men aged 18-26 enrolled at
      three Canadian universities between September 2013 and April 2014. Vaccine
      acceptability assessment was informed by the six-stage decision-making Precaution
      Adoption Process Model (PAPM). We sought information on socio-demographics,
      health behaviors, HPV vaccine benefits and barriers, worry, susceptibility,
      severity related to HPV infection and social norms. HPV and HPV vaccine knowledge
      was measured with validated scales. Psychosocial correlates of HPV vaccine
      acceptability were assessed with bivariate and multivariate multinomial logistic
      regression. Actual and perceived HPV and HPV vaccine knowledge scores were
      calculated. RESULTS: The final sample size was 428. Most male college students
      were unaware that the HPV vaccine could be given to males, unengaged or undecided
      about getting the HPV vaccine. Significant correlates of higher HPV vaccine
      acceptability were: increased HPV knowledge, having discussed the HPV vaccine
      with a healthcare provider, and social norms. Being in an exclusive sexual
      relationship was significantly associated with lower HPV vaccine acceptability.
      Students' actual HPV and HPV vaccine knowledge was low and positively correlated
      to their perception about their HPV knowledge. CONCLUSIONS: We provided a fine
      tuned analysis of psychosocial correlates of HPV vaccine acceptability in college
      males who are in the early stages of HPV vaccine decision-making. Interventions
      are needed to increase HPV and HPV vaccine knowledge in college males.

PMID- 29179878
TI  - Oxidative stress and diabetes: Glucose response in the cROSsfire.
AB  - In this issue of the Biomedical Journal, we discuss the emerging role of reactive
      oxygen species (ROS) in the development of insulin resistance and ultimately type
      2 diabetes. We focus also on research investigating the outcome of in vitro
      fertilization after laproscopic surgery for ovarian endometriosis. Finally, we
      learn the results of a study on the hunt for new probiotic bacteria.

PMID- 29179880
TI  - The etiology of oxidative stress in insulin resistance.
AB  - Insulin resistance is a prevalent syndrome in developed as well as developing
      countries. It is the predisposing factor for type 2 diabetes mellitus, the most
      common end stage development of metabolic syndrome in the United States.
      Previously, studies investigating type 2 diabetes have focused on beta cell
      dysfunction in the pancreas and insulin resistance, and developing ways to
      correct these dysfunctions. However, in recent years, there has been a profound
      interest in the role that oxidative stress in the peripheral tissues plays to
      induce insulin resistance. The objective of this review is to focus on the
      mechanism of oxidative species generation and its direct correlation to insulin
      resistance, to discuss the role of obesity in the pathophysiology of this
      phenomenon, and to explore the potential of antioxidants as treatments for
      metabolic dysfunction.

PMID- 29179879
TI  - P2X4: A fast and sensitive purinergic receptor.
AB  - Extracellular nucleotides have been recognized as important mediators of
      activation, triggering multiple responses via plasma membrane receptors known as
      P2 receptors. P2 receptors comprise P2X ionotropic receptors and G protein
      coupled P2Y receptors. P2X receptors are expressed in many tissues, where they
      are involved in a number of functions including synaptic transmission, muscle
      contraction, platelet aggregation, inflammation, macrophage activation,
      differentiation and proliferation, neuropathic and inflammatory pain. P2X4 is one
      of the most sensitive purinergic receptors (at nanomolar ATP concentrations),
      about one thousand times more than the archetypal P2X7. P2X4 is widely expressed
      in central and peripheral neurons, in microglia, and also found in various
      epithelial tissues and endothelial cells. It localizes on the plasma membrane,
      but also in intracellular compartments. P2X4 is preferentially localized in
      lysosomes, where it is protected from proteolysis by its glycosylation. High ATP
      concentration in the lysosomes does not activate P2X4 at low pH; P2X4 gets
      activated by intra-lysosomal ATP only in its fully dissociated tetra-anionic
      form, when the pH increases to 7.4. Thus, P2X4 is functioning as a Ca2+-channel
      after the fusion of late endosomes and lysosomes. P2X4 modulates major
      neurotransmitter systems and regulates alcohol-induced responses in microglia.
      P2X4 is one of the key receptors mediating neuropathic pain. However, injury
      induced upregulation of P2X4 expression is gender dependent and plays a key role
      in pain difference between males and females. P2X4 is also involved in
      inflammation. Extracellular ATP being a pro-inflammatory molecule, P2X4 can
      trigger inflammation in response to high ATP release. It is therefore involved in
      multiple pathologies, like post-ischemic inflammation, rheumatoid arthritis,
      airways inflammation in asthma, neurodegenerative diseases and even metabolic
      syndrome. Although P2X4 remains poorly characterized, more studies are needed as
      it is likely to be a potential therapeutic target in these multiple pathologies.

PMID- 29179881
TI  - Chang Gung Research Database: A multi-institutional database consisting of
      original medical records.
AB  - BACKGROUND: The Chang Gung Research Database (CGRD) is a de-identified database
      derived from original medical records of Chang Gung Memorial Hospital (CGMH),
      which comprises seven medical institutes located from the northeast to southern
      regions of Taiwan. The volume of medical services performed in CGMH is large, and
      clinical and scientific studies based on the CGRD are reported to be of high
      quality. However, the CGRD as a useful database for research has not been
      analyzed before. The objective of the study was to analyze the CGRD with regard
      to its characteristics and coverage of Taiwan's population. METHODS: We performed
      a nationwide cohort study using population-based data from the Taiwan National
      Health Insurance Research Database (NHIRD). All patients who had any medical
      record of outpatient visits or admission between January 1, 1997, and December
      31, 2010, were included, and the sex ratio, age distribution, socioeconomic
      status, urbanicity, severity of illness, prevalence of specific disease, and
      coverage of the CGRD were analyzed. RESULTS: The sex ratio, age distribution,
      socioeconomic status, and urbanicity of the population of the CGRD are different
      from those of Taiwan NHIRD and medical centers in Taiwan (all the pairwise p <
      0.05). The severity of comorbidities, and prevalence of specific diseases of the
      population of the CGRD are significantly higher than those of Taiwan NHIRD and
      medical centers in Taiwan for both outpatient and inpatient samples (all the
      pairwise p < 0.05). The overall coverage of the CGRD was 21.2% for outpatients
      and 12.4% for inpatients. The disease-specific coverage of the CGRD was 27-34%
      for outpatients and 14-21% for inpatients. CONCLUSIONS: The CGRD is a multi
      institutional, original medical record-based research database with high overall
      and disease-specific coverage of Taiwan. The population of the CGRD has
      significantly higher severity of comorbidities, and prevalence of specific
      diseases than those of Taiwan NHIRD and medical centers in Taiwan.

PMID- 29179882
TI  - Probiotic potential of Lactobacilli with antagonistic activity against pathogenic
      strains: An in vitro validation for the production of inhibitory substances.
AB  - BACKGROUND: Probiotics, live cells with different beneficiary characteristics,
      have been extensively studied and explored commercially in many different
      products in the world. Their benefits to human and animal health have proven in
      hundreds of scientific studies. Based on rich bibliographic material, Curd is the
      potential source of probiotic Lactobacilli. METHOD: The aim of the present study
      was to observe Lactobacilli with probiotic potential activities from different
      curd samples for isolation, identification and characterization of Lactobacillus
      species. RESULTS: Among the samples, thirty lactic acid bacterial strains were
      isolated, sixteen (16/30) best Lactobacillus isolates were selected by
      preliminary screening as potential probiotic for acid and bile tolerance, further
      confirmed using 16s rRNA identification. All the selected Lactobacillus isolates
      were then characterized in vitro for their probiotic characteristics and
      antimicrobial activities against pathogens and aggregation studies. The results
      indicated that selected potential probiotic isolates (T2, T4 and T16) were
      screened and confirmed as Lactobacillus. The isolates produced positive tolerance
      to excited pH, NaCl and bile salts, also revealed noticeable antimicrobial
      activities against pathogens. All the Lactobacillus isolates were susceptible to
      clinical antibiotics used. Besides, T2 isolate was constituted to retain stronger
      auto and co-aggregation and cell surface hydrophobicity capacity. CONCLUSION:
      Based on the drawn results, T2, T4 and T16 Lactobacillus isolates were recognised
      as ideal, potential in vitro antimicrobial probiotic isolates against pathogens
      and studies are needed further in-vivo assessment and human health benefits in
      their real-life situations.

PMID- 29179883
TI  - Shifting trend of tubercular lymphadenitis over a decade - A study from eastern
      region of India.
AB  - BACKGROUND: The incidence of tuberculosis (TB) is changing in India. The
      commonest extra pulmonary manifestation of TB is tuberculous lymphadenitis. AIMS
      AND OBJECTIVES: To detect changes in occurrence of TB lymphadenitis by comparing
      current data with that from 10 years back. METHODS: Fine Needle Aspiration
      Cytology (FNAC) findings of patients presenting with lymphadenopathy between
      January 2014 and December 2015 were included in the study as current data. Cases
      of TB lymphadenitis were analysed for cyto-morphological patterns and frequency
      of acid fast bacilli (AFB) positivity. Cytological data of patients with
      lymphadenopathy between January 2002 and December 2003, were collected from
      records. Subsequently, comparison was done between previous data and current
      observation. RESULTS: Total 302 cases of lymphadenopathy were included in 2014
      and 2015. Tuberculous lymphadenitis accounted for 96 (31.7%) cases, among which
      AFB was present in 47 (49%) cases. Data collected from registers of the years
      2002 and 2003 included 318 cases where tuberculous lymphadenitis accounted for
      161 (50.6%) cases and AFB was detected in 101 (63%) patients. Maximum AFB
      positivity was found in smears with caseous necrosis only. CONCLUSION: Presently
      occurrence of TB lymphadenopathy has reduced compared to the period of 2002-2003.
      Despite this declining trend, the disease continues to be one of the leading
      causes of lymphadenopathy in both periods.

PMID- 29179884
TI  - Mortality pattern in otorhinolaryngology ward: A 5 years retrospective study at
      an urban tertiary health care center in India.
AB  - BACKGROUND: To recognize deaths in the otorhinolaryngology indoor wards,
      determine the reason behind the mortalities and recommend modifications for
      betterment of patient care and surgical outcomes. METHOD: Data was collected from
      the mortality register, operation theatre registers, ward registers and case
      notes of patients declared dead at an urban tertiary health care center in India
      for a period of 5 years; from January 2012 to December 2016. The data included
      date of admission, age, sex, educational status, residence, and clinical
      diagnosis, course of hospital stay and medical cause of death. Data acquired was
      reviewed and statistically interpreted and presented in graphical and descriptive
      formats. RESULTS: 6157 admissions were made in otorhinolaryngology (ENT) ward in
      the 5 year period which included 3969 males and 2188 female patients. 58 deaths
      were recorded during this period which gives overall death per admission crude
      mortality rate of 9.42% at an average of about 12 (11.60) deaths per year. The
      major causes of death were malignancy and septicemia. CONCLUSION: The
      significance of health education, aggressive healthcare campaigns, enhancement of
      healthcare services and wide accessibility of healthcare services to remote areas
      has been emphasized. Role of structured study and protocols in the management of
      serious cases is highlighted along with the need for prompt referral and better
      interdepartmental cooperation.

PMID- 29179886
TI  - The Oncoming Challenge of Homo Superior.

PMID- 29179885
TI  - Bilaterality of ovarian endometriomas does not affect the outcome of in vitro
      fertilization/intracytoplasmic sperm injection in infertile women after
      laparoscopic cystectomy.
AB  - BACKGROUND: To assess whether the unilateral or bilateral lesions can affect
      ovarian reserve and pregnancy outcome in in vitro fertilization/intracytoplasmic
      sperm injection (IVF/ICSI) in infertility patients underwent laparoscopic
      cystectomy. METHODS: A total of 148 IVF/ICSI cycle in patients who had undergone
      laparoscopic cystectomy for unilateral or bilateral endometriomas were reviewed
      retrospectively. There were 103 cycles where laparoscopic cystectomy had been
      carried out for unilateral endometriomas and 45 cycles after bilateral-side
      surgery. Primary outcome measures were ovarian reserve and ovarian response.
      Secondary outcome measures were the implantation rate, clinical pregnancy rate,
      and live birth rate. RESULTS: The number of dominant follicle on the day of human
      chorionic gonadotropin (hCG) administration (5.2 +/- 3.1 vs. 4.2 +/- 2.7; p =
      0.048), and oocytes retrieved (10.0 +/- 6.9 vs. 7.6 +/- 6.6; p = 0.047) were
      significantly lower in the bilateral-side group compare with the unilateral-side
      group. However, the mean number of antral follicle count, metaphase II oocytes,
      the doses of gonadotropin used, fertilization rate, the rate of good quality
      embryos transferred, implantation rate and clinical pregnancy, live-birth rate
      and miscarriage rate were similar between the two groups. CONCLUSION: There were
      no associations among the bilaterality of ovarian endometriomas, ovarian reserve
      and pregnancy outcomes in IVF/ICSI cycles. However, bilateral ovarian
      endometriomas after laparoscopic cystectomy may impair ovarian response as
      compared to unilateral ovarian endometrioma.

PMID- 29179887
TI  - Biomechanical Analysis of Dance for Parkinson's Disease: A Paradoxical Case Study
      of Balance and Gait Effects?
AB  - OBJECTIVES: This study aimed to measure the effects of a dance training program
      on subjective and objective balance and gait measures in a person with
      Parkinson's disease. DESIGN AND SETTING: The participant was measured via
      clinical scales and biomechanical balance and gait analyses pre- and post-16
      weeks of dance participation at the University Center for Arts in Medicine. The
      dance program consisted of 75 minute sessions three days a week. RESULTS:
      Improved clinical scales included the Schwab and England scale (+10%), falls
      efficacy scale (-11 points), six-minute walk (+15.54m), and timed up and go
      (1.38s). Balance measures during three conditions (eyes open, eyes closed, and
      narrow stance) all demonstrated an increase (24-112%) in center of pressure path
      length, velocity (anteroposterior and mediolateral), sway area, and approximate
      entropy (anteroposterior and mediolateral). Spatiotemporal gait parameters
      improved during forward walking: velocity (+0.12m/s), cadence (+3.89steps/min),
      double support time (-2.02%), stride length (+0.07m), stride time (-0.03s), and
      backward walking: single support (+3.47%), double support (-7.0%), swing time
      (+3.4%), and stance time (-3.4%). CONCLUSIONS: Classic interpretation of the
      above measures may indicate a detriment in biomechanical balance effects
      concomitant with an improvement in gait. Alternative explanations explored
      suggest this paradox to be illusory.

PMID- 29179888
TI  - Secondary Prevention of CVD in LMIC: Care for the Growing Affected Population.

PMID- 29179889
TI  - The Burden of Heart, Lung, and Blood Diseases in the United States, 1990 to 2016:
      Perspectives from the National Heart, Lung, and Blood Institute.

PMID- 29179890
TI  - Diabetic lumbosacral radiculoplexus neuropathy succesfully treated with
      intravenous immunoglobulins.

PMID- 29179891
TI  - Blistering lesions on a 81 year old woman.

PMID- 29179892
TI  - Update on osteoporosis treatment.
AB  - Treatment of osteoporosis should be directed primarily towards secondary
      prevention of fractures. The occurrence of drug-related adverse effects for the
      treatment of osteoporosis has led to a reevaluation of the indications, the
      duration of treatment and even withdrawal of some drugs from the market. This
      review has been made from different patient profiles that practitioners will find
      in usual practice; from patients with hip fracture with cognitive impairment,
      limitation of their day-to-day living activities and comorbidities, to active
      patients without any limitations; patients with vertebral fractures and non
      vertebral fractures where secondary prevention is highly important. In general,
      antiresorptive drugs (alendronate and risedronate) will be the first choice.
      Zoledronate or denosumab will be indicated in cases of digestive intolerance,
      poor adherence or an increased risk of hip fracture. Teriparatide will be
      indicated to patients with 2or more previous vertebral fractures or very low bone
      density.

PMID- 29179893
TI  - Chronic necrotizing pulmonary aspergillosis in an immunocompetent patient.

PMID- 29179895
TI  - Letter from the Editor.

PMID- 29179896
TI  - Malignant Pleural Mesothelioma: Diagnosis, Staging, Pitfalls and Follow-up.
AB  - Malignant pleural mesothelioma is the most common primary neoplasm of the pleura.
      Imaging evaluation is essential in diagnosis, staging, and assessment of
      treatment response in malignant pleural mesothelioma. Computed tomography is the
      most commonly used modality for tumor staging. Assessment of tumor extension and
      lymph node involvement is essential in imaging evaluation as locally advanced
      tumors are amenable to resection. Knowledge of the full imaging spectrum of this
      rare disease, differential diagnosis, staging classification, and the current
      guidelines for diagnostic evaluation and follow-up are essential in accurate
      interpretation to optimize patient management.

PMID- 29179897
TI  - Positron Emission Tomography/Computed Tomography in Esophageal Carcinoma:
      Applications and Limitations.
AB  - Squamous cell carcinoma and adenocarcinoma represent approximately 98% of
      esophageal malignant tumors. During the last 30 years, the incidence of
      adenocarcinoma has increased in Western countries (including the USA) where
      adenocarcinoma currently represents more than 60% of esophageal malignancies,
      although, worldwide, squamous cell carcinoma continues to be the predominant
      histologic type. Integrated positron emission tomography or computed tomography
      with 2-[fluorine18] fluro-2-deoxy-d-glucose is used in many institutions
      routinely as a tool in the initial staging and then repeated after therapy for
      the assessment of response to neoadjuvant therapy and detection of recurrent
      disease in patients with esophageal carcinoma. As with any other imaging
      modality, 2-[fluorine18] fluro-2-deoxy-d-glucose-positron emission tomography or
      computed tomography has strengths and limitations that should be understood in
      order to maximize its utility.

PMID- 29179894
TI  - [Preventative and therapeutic relapse strategies after allogeneic hematopoietic
      stem cell transplantation: Guidelines from the Francophone society of bone marrow
      transplantation and cellular therapy (SFGM-TC)].
AB  - Disease relapse remains the first cause of mortality of hematological
      malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT).
      The risk of recurrence is elevated in patients with high-risk cytogenetic or
      molecular abnormalities, as well as when allo-HCT is performed in patients with
      refractory disease or with persistent molecular or radiological (PET-CT scan)
      residual disease. Within the frame of the 7th annual workshops of the francophone
      society for bone marrow transplantation and cellular therapy, the working group
      reviewed the literature in order to elaborate unified guidelines for the
      prevention and treatment of relapse after allo-HCT. For high risk AML and MDS, a
      post transplant maintenance strategy is possible, using hypomethylating agents or
      TKI anti-FLT3 when the target is present. For Philadelphia positive ALL, there
      was a consensus for the use of post-transplant TKI maintenance. For lymphomas,
      there are no strong data on the use of post-transplant maintenance, and hence a
      preemptive strategy is recommended based on modulation of immunosuppression,
      close follow-up of donor chimerism, and donor lymphocytes infusion. For multiple
      myeloma, even though the indication of allo-HCT is controversial, our
      recommendation is post transplant maintenance using bortezomib, due to its a good
      toxicity profile without increasing the risk of GVHD.

PMID- 29179898
TI  - Imaging of Intrathoracic Paragangliomas.
AB  - Intrathoracic paragangliomas are uncommon and only represent 1%-2% of
      paragangliomas. They are most commonly found in mediastinal compartments
      (aortopulmonary window or posterior mediastinum). Computed tomography, magnetic
      resonance, and specific nuclear medicine radiotracers are routinely used to
      characterize these lesions and help exclude other more common conditions.
      Selective angiography is currently used for preoperative embolization and mapping
      of the vascular supply before surgical resection, rather than for diagnostic
      purposes alone.

PMID- 29179899
TI  - Imaging of Metastases in the Chest: Mechanisms of Spread and Potential Pitfalls.
AB  - Pulmonary and pleural metastases are routinely identified on thoracic computed
      tomography. Pulmonary metastases are the most common pulmonary neoplasms and
      commonly originate from primary malignancies of the lung, breast, colon,
      pancreas, stomach, skin (ie, melanoma), head and neck, and kidney. Metastatic
      disease to the lungs may occur via 3 routes of spread: hematogenous, lymphatic,
      and endobronchial. Pleural metastases most commonly originate from primary
      malignancies of the lung and breast. Mechanisms of pleural metastatic involvement
      include hematogenous spread, direct invasion from a neighboring tumor, and
      retrograde lymphatic spread from the mediastinum. Awareness of the spectrum of
      appearances of metatastic disease in the chest is important in avoiding
      misinterpretation.

PMID- 29179900
TI  - Intra- and Extra-Thoracic Muscle Flaps and Chest Wall Reconstruction Following
      Resection of Thoracic Tumors.
AB  - Improvements in surgical technique over the last decade enable surgeons to
      perform extensive resection and reconstruction in patients presenting with tumors
      involving the soft tissue or bony structures of the chest wall. The type of
      surgical resection and its size, depend on the type of tumor resected and its
      location. In addition to providing a better esthetic result, the reconstruction
      restores support and functionality of the thoracic cage. The approach to chest
      wall repair includes primary closure or reconstruction by using transposition
      flaps, free flaps, prosthetic material, or a mixture of a flap and prosthetic
      material.

PMID- 29179902
TI  - Mediastinal (Epipericardial) Fat Necrosis: An Overlooked and Little Known Cause
      of Acute Chest Pain Mimicking Acute Coronary Syndrome.
AB  - Necrosis of the fat adjacent to the heart, referred to as pericardial fat
      necrosis, epipericardial fat necrosis, and mediastinal fat necrosis, is a rare,
      self-limited condition. It presents as a sudden onset of severe chest pain that
      mimics symptoms of pulmonary embolism and acute coronary syndrome. Computed
      tomography (CT) findings are quite typical and consist of a round- or oval-shaped
      mass-like lesion containing soft tissue and fat density components in the
      cardiophrenic space. Lack of familiarity with this condition has led in the past
      to surgical interventions to remove the mass-like mediastinal fat necrosis. Until
      the early 2000s, surgical removal of these lesions was deemed the treatment of
      choice, to exclude a neoplasm. However, the observation that the CT findings of
      the paracardiac mass resemble fat necrosis seen in other parts of the body and
      its involution on follow-up CT has led to the realization that the process is a
      benign and self-limiting one. A dramatic shift in the paradigm of treatment has
      ensued and surgical treatment is no longer advocated. Awareness of this condition
      is, therefore, vital so as to diagnose it accurately and avoid unnecessary future
      surgical interventions.

PMID- 29179901
TI  - CT Imaging of Complications Associated with Continuous-Flow Left Ventricular
      Assist Devices (LVADs).
AB  - Heart failure is becoming increasingly prevalent, and more patients are being
      treated with left ventricular assist devices (LVADs), either as a bridge to
      transplant or as destination therapy. The use of continuous-flow LVADs is on the
      rise. LVAD therapy is associated with several classes of complications, including
      bleeding, thrombosis, and infection. CT imaging can be used effectively to
      diagnose LVAD complications, including mediastinal hematomas and pericardial,
      abdominal wall, and retroperitoneal hemorrhage, inflow and outflow graft and
      aortic thrombi, and driveline and pump pocket infections. CT can also be helpful
      in cases of device malfunction and can detect outflow graft kinking and inflow
      cannula misalignment. When interpreting CT scans in patients with LVADs,
      accessory materials implanted with the device should not be mistaken for
      hemorrhage or calcification. With training in recognizing LVAD complications,
      radiologists can play an important role in the evaluation of patients with heart
      failure.

PMID- 29179903
TI  - Thoracolithiasis-Computed Tomography Findings of Intrapleural Loose Bodies.
AB  - Thoracoliths are rare benign intrapleural loose bodies, often containing
      calcification, that are mobile in the pleural cavity. The presence of these
      intrapleural nodules is referred to as thoracolithiasis. The exact etiology of
      thoracoliths is unknown, but they presumably result from a prior episode of
      mediastinal (epipericardial) fat necrosis. Thoracoliths are usually asymptomatic
      and incidentally encountered on computed tomography. However, they sometimes pose
      diagnostic challenges, as a thoracolith may be located within a pleural fissure,
      and is then indistinguishable from a pulmonary nodule. In addition, migration and
      rotation of thoracoliths within the pleural space observed on serial computed
      tomography studies has been reported to raise concern that these might be
      neoplastic lesions, leading to their surgical removal. Awareness of this benign
      condition is important in order to avoid unnecessary invasive procedures.

PMID- 29179904
TI  - Corrigendum to "Seroprevalence, disease awareness, and risk factors for Toxocara
      canisinfection among primary schoolchildren in Makoko, an urban slumcommunity in
      Nigeria" [Acta Tropica 146 (2015) 135-140].

PMID- 29179906
TI  - Diagnostic challenges in papillary lesions of the breast.
AB  - Papillary lesions of the breast comprise a heterogeneous group of diseases
      ranging from benign and atypical lesions to malignant tumours including non
      invasive and invasive entities. Although diagnosis of papillary lesions featuring
      typical histological features is straightforward, a proportion shows overlapping
      features, posing diagnostic challenges. In addition to being uncommon, the
      excellent behaviour of papillary tumours reduces the distinguishing value of
      individual histological features and increases the subjectivity of interpretation
      of various diagnostic features. Therefore the overall categorisation, which is
      based on a constellation of subjective features, may vary with subsequent
      management implications. Concordance studies revealed that recognition of
      papillary carcinomas (PC) as a malignant entity by pathologists is high, but
      concordance of its classification into in situ and invasive disease can be
      problematic, as can assessment of prognostic and predictive factors in the
      invasive component. Identification of low nuclear grade atypia within benign
      papillary lesions and its classification into atypia or in situ carcinoma may
      also pose a diagnostic challenge. Although immunohistochemistry is helpful in
      evaluation of benign and atypical lesions it has a limited utility in
      differentiating the majority of PC as non-invasive or invasive disease.
      Pathologists should be aware of the various entities and the differential
      diagnosis of each entity, the existence of lesions with overlapping features and
      should follow the updated guideline recommendation for their diagnosis and
      management. These rare lesions usually require additional diagnostic work-up and
      difficult cases should trigger consensus opinion or expert referral.

PMID- 29179907
TI  - Management and outcomes of isolated paediatric tibial spine fractures.
AB  - Paediatric fractures of the tibial spine are relatively rare and controversy
      remains around how these injuries are best managed (Gans et al., 2014; Hargrove
      et al., 2004). Consequently most non-specialised paediatric units have limited
      experience of managing these injuries. This study aims to review the management
      and outcomes of isolated paediatric tibial spine fractures in a tertiary
      paediatric orthopaedic centre between 2008 and 2016. Data were collected on
      patient demographics, mechanism of injury, imaging, Meyers and McKeever grade of
      injury (Meyers and McKeever), management and outcomes, including Cincinnati and
      Lysholm-Tegner knee scores at a mean of 36 months post-operatively. 40 patients
      were included, 21 were male and the mean age was 11.8 years. 3 cases were Meyers
      and McKeever type I, 13 were type II and 24 were type III. 30 underwent operative
      management comprising of open reduction and single screw fixation, with or
      without a washer. 9 patients underwent subsequent metalwork removal at a mean of
      10 months post-operatively. 10 underwent non-operative management, consisting of
      cast immobilisation and bracing. 33 patients (83%) were available for follow up.
      No statistically significant differences were seen in either outcome score
      between those treated operatively or non-operatively, or between different grades
      of injury, or if metalwork were removed or not. Our study shows good functional
      outcomes following paediatric tibial spine fracture. We advocate the use of CT to
      assess fracture displacement to help guide management. We have shown type I and
      reducible type II injuries can successfully be managed conservatively and non
      reducible type II and type III injuries can be successfully treated with open
      reduction and single screw fixation. In our experience post-operative knee
      stiffness can persist for up to 6 months but generally improves. Metalwork
      removal was only indicated if the patient had on going stiffness after this time
      or if they had on going pain.

PMID- 29179908
TI  - Preperitoneal pelvic packing is effective for hemorrhage control in open pelvic
      fractures.
AB  - BACKGROUND: Open pelvic fractures are life-threatening injuries. Preperitoneal
      pelvic packing (PPP) has been suggested to be ineffective for hemorrhage control
      in open pelvic fractures. We hypothesize that PPP is effective at hemorrhage
      control in patients with open pelvic fractures and reduces mortality. METHODS:
      Patients undergoing PPP from 2005 to 2015 were analyzed. Patients with open
      pelvic fractures were defined as direct communication of the bony injury with
      overlying soft tissue, vagina, or rectum. RESULTS: During the 10-year study, 126
      patients underwent PPP; 14 (11%) sustained an open pelvic fracture. After PPP, 1
      patient (7%) underwent angioembolization with a documented arterial blush. PPP
      controlled pelvic hemorrhage in all patients. Overall mortality rate was 7% with
      one death due to traumatic brain injury. CONCLUSIONS: PPP is effective for
      hemorrhage control in patients with open pelvic fractures. PPP should be used in
      a standard protocol for hemodynamically unstable patients with pelvic fractures
      regardless of associated perineal injuries.

PMID- 29179909
TI  - Surgical interns: Preparedness for opioid prescribing before and after a training
      intervention.
AB  - INTRODUCTION: Exposure to pain management curriculum in medical school is
      currently variable. This paper reports on formal prescribing education, self
      perceived prescribing readiness, and prescribing practices among incoming
      surgical residents before and after a pain management training session. METHODS:
      Pre-residency survey of thirty surgical interns at a single urban medical center,
      followed by a repeat survey after an educational session on prescription writing
      and opioid abuse. RESULTS: Thirty-three percent of respondents had formal
      education on prescription writing in medical school. Median subjective
      preparedness to write an opioid prescription was 1.5 (range 1-10) on a 1-10
      Likert scale. Ranges of morphine milligram equivalents (MME) prescribed varied
      from 420-2700 MME for 8 mock surgical scenarios. Post-training, median subjective
      preparedness increased to 3.5 (range 1-6) and prescription accuracy (the
      inclusion of a medication, dose, frequency, and duration) improved from 75% to
      97% (p < 0.001). Overall, 90% of interns found the training session useful.
      CONCLUSION: Most surgical interns were not trained in prescribing narcotics in
      medical school. Improved pain management curriculum is necessary to assure safe
      and consistent opioid prescriptions.

PMID- 29179910
TI  - Meaning in meaninglessness: The propensity to perceive meaningful patterns in
      coincident events and randomly arranged stimuli is linked to enhanced attention
      in early sensory processing.
AB  - Perception of objectively independent events or stimuli as being significantly
      connected and the associated proneness to perceive meaningful patterns constitute
      part of the positive symptoms of schizophrenia, which are associated with altered
      attentional processes in lateralized speech perception. Since perceiving
      meaningful patterns is to some extent already prevalent in the general
      population, the aim of the study was to investigate whether the propensity to
      experience meaningful patterns in co-occurring events and random stimuli may be
      associated with similar altered attentional processes in lateralized speech
      perception. Self-reported and behavioral indicators of the perception of
      meaningful patterns were assessed in non-clinical individuals, along with EEG
      auditory evoked potentials during the performance of an attention related
      lateralized speech perception task (Dichotic Listening Test). A greater
      propensity to perceive meaningful patterns was associated with higher N1
      amplitudes of the evoked potentials to the onset of the dichotically presented
      consonant-vowel syllables, indicating enhanced automatic attention in early
      sensory processing. The study suggests that more basic mechanisms in how people
      associate events may play a greater role in the cognitive biases that are
      manifest in personality expressions such as positive schizotypy, rather than that
      positive schizotypy moderates these cognitive biases directly.

PMID- 29179911
TI  - Growth hormone and insulin-like growth factor 1 secretions in eating disorders:
      Correlations with psychopathological aspects of the disorders.
AB  - Hormonal alterations in Eating Disorders (ED) may result from the biochemical
      stress of malnutrition/starvation. The correlations between some hormonal
      impairments, particularly of the somatotropic axis, and the psychopathological
      aspects of ED are still undefined. We measured the plasma concentrations of the
      somatotropic hormone (GH) and the insulin-like growth factor-1 (IGF-1) in 136
      patients with various forms of ED, 65 with restricted Anorexia Nervosa (ANR), 19
      with bingeing-purging Anorexia Nervosa (ANBP), 12 with purging-non binging
      Anorexia Nervosa (ANP), 26 with Bulimia Nervosa (BN), 8 with ED not otherwise
      specified-anorexic type (EDNOS-AN), 7 with ED not otherwise specified-bulimic
      type (EDNOS-BN) and in 30 healthy controls. Psychological assessment of patients
      and controls was performed using two outpatient rating scales, the Eating
      Disorder Inventory-2 (EDI-2) and the Symptom Checklist-90 (SCL-90). Significant
      negative or positive correlations were observed between GH-IGF-1 concentrations
      and impairments on several EDI-2 subscales (drive for thinness, body
      dissatisfaction, interoceptive awareness, sense of ineffectiveness, interpersonal
      distrust, maturity fear) and on SCL-90 subitems (depression, hostility,
      obsessivity compulsivity, anxiety), suggesting a possible hormonal modulatory
      effect on specific aspects of ED psychopathology.

PMID- 29179912
TI  - Filling the void: a low-cost, high-yield approach to addressing incidental
      findings in trauma patients.
AB  - BACKGROUND: Incidental findings are prevalent in imaging but often go unreported
      to patients. Such unreported findings may present the potential for harm as well
      as medico-legal ramifications. METHODS: A chart review of trauma patients was
      undertaken over a year. Systems-based changes were made utilizing our electronic
      medical record system and our staff protocols to improve the disclosure of
      clinically relevant incidental findings to patients. RESULTS: During the
      preintervention period, 674 charts were reviewed. Trauma patients had a rate of
      incidental findings of 70%, and 36% of patients had clinically relevant
      incidentals. Rates of follow-up recommendation and disclosure to patients were
      22% and 27%, respectively. In the postintervention period, of the 648 charts were
      reviewed, the rates of a clinically relevant incidental finding were 35%, but the
      rates of follow-up recommendation and disclosure to patients were 68% and 85%,
      respectively. CONCLUSION: Incidental findings are more prevalent herein than
      previously reported. With simple changes and minimal resources, clinically
      relevant and important improvement in reporting incidental findings can be made
      to mitigate the harm and medico-legal impact of an incidental finding going
      unreported.

PMID- 29179913
TI  - Discussion.

PMID- 29179914
TI  - Re-implanting the superior mesenteric artery on the infra-renal aorta.

PMID- 29179915
TI  - The impact of the aging population and incidence of cancer on future projections
      of general surgical workforce needs.
AB  - BACKGROUND: Assessments of the future general surgery workforce continue to
      project substantial shortages of general surgeons. The general surgery workforce
      is targeted currently to maintain a surgeon/population ratio of 6.5-7.5/100,000.
      METHODS: We examined population and age-associated incidence of cancer to
      estimate the number of general surgeons needed for initial surgical treatment of
      the patient with cancer in the year 2035 compared with 2010. We hypothesized that
      the number of general surgeons needed to provide future cancer care will exceed
      the projections of available general surgeons based on current training numbers,
      as well as on population-based ratios alone. RESULTS: The total number of new
      patients with cancers treated by general surgeons is projected to increase 56%
      (511,450 in 2010 to 798,070 in 2035). To maintain the same patient census per
      surgeon, it is estimated that 34,698 general surgeons will be needed. This is an
      increase of 9,198 over that based on current training numbers and 5,300-7,400
      greater than the need projected by population growth alone. CONCLUSION: The
      analysis supports the hypothesis that an increasing incidence of cancer in the
      future will exceed the potential capacity of the general surgeon workforce.
      Regionalization of cancer care may be one solution to projected access issues.

PMID- 29179916
TI  - Real life experience with nivolumab for the treatment of non-small cell lung
      carcinoma: Data from the expanded access program and routine clinical care in a
      tertiary cancer centre-The Netherlands Cancer Institute.

PMID- 29179917
TI  - Editorial 2017.

PMID- 29179919
TI  - How long have you been teaching undergraduate genetics and how have genetics
      courses changed since you were a student or when you first started teaching?

PMID- 29179918
TI  - When DNA Topology Turns Deadly - RNA Polymerases Dig in Their R-Loops to Stand
      Their Ground: New Positive and Negative (Super)Twists in the Replication
      Transcription Conflict.
AB  - Head-on replication-transcription conflict is especially bitter in bacterial
      chromosomes, explaining why actively transcribed genes are always co-oriented
      with replication. The mechanism of this conflict remains unclear, besides the
      anticipated accumulation of positive supercoils between head-on-conflicting
      polymerases. Unexpectedly, experiments in bacterial and human cells reveal that
      head-on replication-transcription conflict induces R-loops, indicating
      hypernegative supercoiling [(-)sc] in the region - precisely the opposite of that
      assumed. Further, as a result of these R-loops, both replication and
      transcription in the affected region permanently stall, so the failure of R-loop
      removal in RNase H-deficient bacteria becomes lethal. How hyper(-)sc emerges in
      the middle of a positively supercoiled chromosomal domain is a mystery that
      requires rethinking of topoisomerase action around polymerases.

PMID- 29179921
TI  - Mental health law: revision or reformation?

PMID- 29179922
TI  - Appraising appraisals: role of belief in psychotic experiences.

PMID- 29179923
TI  - Prisoner suicide: a multilevel problem.

PMID- 29179924
TI  - Confusion regarding operant conditioning of the EEG.

PMID- 29179920
TI  - Mitochondrial Genome Engineering: The Revolution May Not Be CRISPR-Ized.
AB  - In recent years mitochondrial DNA (mtDNA) has transitioned to greater prominence
      across diverse areas of biology and medicine. The recognition of mitochondria as
      a major biochemical hub, contributions of mitochondrial dysfunction to various
      diseases, and several high-profile attempts to prevent hereditary mtDNA disease
      through mitochondrial replacement therapy have roused interest in the organellar
      genome. Subsequently, attempts to manipulate mtDNA have been galvanized, although
      with few robust advances and much controversy. Re-engineered protein-only
      nucleases such as mtZFN and mitoTALEN function effectively in mammalian
      mitochondria, although efficient delivery of nucleic acids into the organelle
      remains elusive. Such an achievement, in concert with a mitochondria-adapted
      CRISPR/Cas9 platform, could prompt a revolution in mitochondrial genome
      engineering and biological understanding. However, the existence of an endogenous
      mechanism for nucleic acid import into mammalian mitochondria, a prerequisite for
      mitochondrial CRISPR/Cas9 gene editing, remains controversial.

PMID- 29179925
TI  - Confusion regarding operant conditioning of the EEG - Authors' reply.

PMID- 29179926
TI  - Social exclusion and human rights at the intersection of HIV and severe mental
      illness.

PMID- 29179927
TI  - Social exclusion and human rights at the intersection of HIV and severe mental
      illness - Author's Reply.

PMID- 29179928
TI  - Data do not support sex as addictive.

PMID- 29179929
TI  - Understanding the true economic impact of self-harming behaviour.

PMID- 29179932
TI  - Sarah Carr: coming from a different perspective.

PMID- 29179930
TI  - Understanding the true economic impact of self-harming behaviour - Authors'
      reply.

PMID- 29179933
TI  - Crisis in UK prison mental health.

PMID- 29179934
TI  - Me and my brain.

PMID- 29179935
TI  - Purple.

PMID- 29179937
TI  - Suicide in prisons: an international study of prevalence and contributory
      factors.
AB  - BACKGROUND: Prison suicide rates, rate ratios, and associations with prison
      related factors need clarification and updating. We examined prison suicide rates
      in countries where reliable information was available, associations with a range
      of prison-service and health-service related factors, how these rates compared
      with the general population, and changes over the past decade. METHODS: We
      collected data for prison suicides in 24 high-income countries in Europe,
      Australasia, and North America from their prison administrations for 2011-14 to
      calculate suicide rates and rate ratios compared with the general population. We
      used meta-regression to test associations with general population suicide rates,
      incarceration rates, and prison-related factors (overcrowding, ratio of prisoners
      to prison officers or health-care staff or education staff, daily spend,
      turnover, and imprisonment duration). We also examined temporal trends. FINDINGS:
      3906 prison suicides occurred during 2011-14 in the 24 high-income countries we
      studied. Where there was breakdown by sex (n=2810), 2607 (93%) were in men and
      203 (7%) were in women. Nordic countries had the highest prison suicide rates of
      more than 100 suicides per 100 000 prisoners apart from Denmark (where it was 91
      per 100 000), followed by western Europe where prison suicide rates in France and
      Belgium were more than 100 per 100 000 prisoners. Australasian and North American
      countries had rates ranging from 23 to 67 suicides per 100 000 prisoners. Rate
      ratios, or rates compared with those in the general population of the same sex
      and similar age, were typically higher than 3 in men and 9 in women. Higher
      incarceration rates were associated with lower prison suicide rates (b = -0.504,
      p = 0.014), which was attenuated when adjusting for prison-level variables. There
      were no associations between rates of prison suicide and general population
      suicide, any other tested prison-related factors, or differing criteria for
      defining suicide deaths. Changes in prison suicide rates over the past decade
      vary widely between countries. INTERPRETATION: Many countries in northern and
      western Europe have prison suicide rates of more than 100 per 100 000 prisoners
      per year. Individual-level information about prisoner health is required to
      understand the substantial variations reported and changes over time. FUNDING:
      Wellcome Trust and the UK National Institute for Health Research (NIHR).

PMID- 29179936
TI  - Clinical relevance of appraisals of persistent psychotic experiences in people
      with and without a need for care: an experimental study.
AB  - BACKGROUND: Cognitive models of psychosis propose that appraisals (ie, the
      interpretation and meaning attributed to experiences) are central to the
      transition from anomalous experiences to psychotic symptoms. In the Unusual
      Experiences Enquiry (UNIQUE) study, we investigated the role of appraisals by
      comparing individuals with persistent psychotic experiences without a need for
      care with patients and people without psychotic experiences. METHOD: Eligible
      participants were patients with diagnosed psychotic disorders (clinical group)
      and adults in the general population with persistent psychotic experiences (non
      clinical group) and without psychotic experiences (controls). The appraisals of
      psychotic experiences among people in the non-clinical and clinical groups were
      assessed by an in-depth interview, and appraisals of anomalous experiences
      induced by three experimental tasks were compared between all groups. FINDINGS:
      We recruited 259 participants, 84 in the clinical group, 92 in the non-clinical
      group, and 83 controls. The clinical group was more likely than the non-clinical
      group to display paranoid, personalising interpretations of their psychotic
      experiences (p<0.008; p values are Sidak adjusted to account for multiple
      testing) and less likely to have normalising (p<0.008) and supernatural (p=0.039)
      explanations. The clinical group also appraised their psychotic experiences as
      being more negative, dangerous, and abnormal and less controllable than the non
      clinical group (all p<0.005), but groups did not differ for attributions of
      general externality (p=0.44). For experimentally induced anomalous experiences,
      the clinical group endorsed more threatening appraisals on all tasks than the non
      clinical group (p<0.003), who did not differ from the control group (p=0.07-0.6).
      The pattern was similar for ratings of salience, distress, personal relevance,
      global threat, and incorporation of the induced experiences into participants'
      own psychotic experiences. INTERPRETATION: We provide robust evidence that the
      way psychotic experiences are appraised differs between individuals with and
      without a need for care, supporting cognitive models of psychosis. Specifically,
      the absence of paranoid and threatening appraisals might protect against
      persistent psychotic experiences becoming clinically relevant. FUNDING: UK
      Medical Research Council.

PMID- 29179939
TI  - Corrections.

PMID- 29179938
TI  - Assessment of outpatient commitment in randomised trials.

PMID- 29179940
TI  - Corrections.

PMID- 29179941
TI  - Randomised controlled trials and outpatient commitment.

PMID- 29179942
TI  - Randomised controlled trials and outpatient commitment.

PMID- 29179943
TI  - Ensuring Access to Needed Follow-Up Care: An Emergency Department Quality Metric
      and Shared Responsibility.

PMID- 29179944
TI  - Ion-induced modification of the sucrose network and its impact on melting of
      freeze-dried liposomes. DSC and molecular dynamics study.
AB  - Disaccharides play an important role in survival of anhydrobiotic organisms
      during extreme environmental conditions. A key protection feature is their
      capability to form the hydrogen bond (HB) network in a similar fashion as the one
      made by water. Since various ions also affect the HB network in completely
      hydrated systems, it is of a great interest to understand how they impact
      preservation when incorporated in a disaccharide network. To address this, we
      employ a combination of experimental and modeling techniques to study behavior of
      multilamellar 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes freeze
      dried with sucrose in presence of NaCl or NaH2PO4.H2O at various concentrations
      (0.01-1M). Differential scanning calorimetry (DSC) was employed in order to
      determine the cooperative unit size (CUS), the number of lipid molecules that
      constitute a domain of cooperative motion in the liposome, and the melting
      temperature (Tm). In the absence of salt CUS was estimated to be 122+/-12,
      whereas in the presence of NaCl CUS increases more (347+/-34 for c=1M) than for
      NaH2PO4.H2O (193+/-26 for 1M). When it comes to Tm, the situation is reversed;
      NaCl induces increase by about 1K, while NaH2PO4.H2O by about 10K. These findings
      clearly demonstrate how different interaction forces-hydrogen bonding, charge
      pairing, and van der Waals interactions between acyl chains-affect CUS and Tm.
      Their interplay and contribution of particular interaction was further analyzed
      with molecular dynamics (MD) simulations. This analysis demonstrated that the HB
      network of DMPC and sucrose is partially disrupted in the presence of NaCl ions,
      and even to a greater extent in the case of NaH2PO4.H2O ions. Notably, H2PO4-
      ions outcompete and replace the sucrose molecules at the DMPC surface, which in
      turn alters the nature of the DMPC-surrounding interactions, from a weaker HB
      dominated to a stronger CP-dominated interaction network.

PMID- 29179945
TI  - To solve old problems, study new research organisms.

PMID- 29179947
TI  - Why we need mechanics to understand animal regeneration.
AB  - Mechanical forces are an important contributor to cell fate specification and
      cell migration during embryonic development in animals. Similarities between
      embryogenesis and regeneration, particularly with regards to pattern formation
      and large-scale tissue movements, suggest similarly important roles for physical
      forces during regeneration. While the influence of the mechanical environment on
      stem cell differentiation in vitro is being actively exploited in the fields of
      tissue engineering and regenerative medicine, comparatively little is known about
      the role of stresses and strains acting during animal regeneration. In this
      review, we summarize published work on the role of physical principles and
      mechanical forces in animal regeneration. Novel experimental techniques aimed at
      addressing the role of mechanics in embryogenesis have greatly enhanced our
      understanding at scales from the subcellular to the macroscopic - we believe the
      time is ripe for the field of regeneration to similarly leverage the tools of the
      mechanobiological research community.

PMID- 29179948
TI  - Large Deletions Targeting the Triple-Helical Domain of Collagen VII Lead to Mild
      Acral Dominant Dystrophic Epidermolysis Bullosa.

PMID- 29179949
TI  - Antisense Long Non-Coding RNAs Are Deregulated in Skin Tissue of Patients with
      Systemic Sclerosis.
AB  - Systemic sclerosis is an autoimmune disease characterized by fibrosis of skin and
      multiple organs of which the pathogenesis is poorly understood. We studied
      differentially expressed coding and non-coding genes in relation to systemic
      sclerosis pathogenesis with a specific focus on antisense non-coding RNAs. Skin
      biopsy-derived RNAs from 14 early systemic sclerosis patients and six healthy
      individuals were sequenced with ion-torrent and analyzed using DEseq2. Overall,
      4,901 genes with a fold change >1.5 and a false discovery rate <5% were detected
      in patients versus controls. Upregulated genes clustered in immunologic, cell
      adhesion, and keratin-related processes. Interestingly, 676 deregulated non
      coding genes were detected, 257 of which were classified as antisense genes.
      Sense genes expressed opposite of these antisense genes were also deregulated in
      42% of the observed sense-antisense gene pairs. The majority of the antisense
      genes had a similar effect sizes in an independent North American dataset with
      three genes (CTBP1-AS2, OTUD6B-AS1, and AGAP2-AS1) exceeding the study-wide
      Bonferroni-corrected P-value (PBonf < 0.0023, Pcombined = 1.1 * 10-9, 1.4 * 10-8,
      1.7 * 10-6, respectively). In this study, we highlight that together with coding
      genes, (antisense) long non-coding RNAs are deregulated in skin tissue of
      systemic sclerosis patients suggesting a novel class of genes involved in
      pathogenesis of systemic sclerosis.

PMID- 29179950
TI  - Astaxanthin-antioxidant impact on excessive Reactive Oxygen Species generation
      induced by ischemia and reperfusion injury.
AB  - Oxidative stress induced by Reactive Oxygen Species (ROS) was shown to be
      involved in the pathogenesis of chronic diseases such as cardiovascular
      pathologies. Particularly, oxidative stress has proved to mediate abnormal
      platelet function and dysfunctional endothelium-dependent vasodilatation
      representing a key factor in the progression of ischemic injuries. Antioxidants
      like carotenoids have been suggested to contribute in their prevention and
      treatment. Astaxanthin, a xanthophyll carotenoid produced naturally and
      synthetically, shows interesting antioxidant and anti-inflammatory properties. In
      vivo studies applying different models of induced ischemia and reperfusion (I/R)
      injury confirm astaxanthin's protective action after oral or intravenous
      administration. However, some studies have shown some limitations after oral
      administration such as low stability, bioavailability and bioefficacy, revealing
      a need for the implementation of new biomaterials to act as astaxanthin vehicles
      in vivo. Here, a brief overview of the chemical characteristics of astaxanthin,
      the carrier systems developed for overcoming its delivery drawbacks and the
      animal studies showing its potential effect to treat I/R injury are presented.

PMID- 29179946
TI  - Learning from regeneration research organisms: The circuitous road to scar free
      wound healing.
AB  - The skin is the largest organ in the body and plays multiple essential roles
      ranging from regulating temperature, preventing infection and ultimately defining
      who we are physically. It is a highly dynamic organ that constantly replaces the
      outermost cells throughout life. However, when faced with a major injury, human
      skin cannot restore a significant lesion to its original functionality, instead a
      reparative scar is formed. In contrast to this, many other species have the
      unique ability to regenerate full thickness skin without formation of scar
      tissue. Here we review recent advances in the field that shed light on how the
      skin cells in regenerative species react to injury to prevent scar formation
      versus scar forming humans.

PMID- 29179951
TI  - ROS-dependent Atg4 upregulation mediated autophagy plays an important role in Cd
      induced proliferation and invasion in A549 cells.
AB  - Cadmium (Cd) is a toxic heavy metal that is widely used in industry and
      agriculture. In this study the role of autophagy in Cd-induced proliferation,
      migration and invasion was investigated in A549 cells. Exposure to Cd (2 MUM)
      significantly increased reactive oxygen species (ROS) production, induced
      autophagy and enhanced cell growth, migration and invasion in A549 cells. Western
      blot analysis showed that the expression of autophagy-related proteins, LC3-II,
      Beclin-1 and Atg4 and invasion-related protein MMP-9 were upregulated in Cd
      treated cells. N-acetyl cysteine (NAC) markedly prevented Cd-induced
      proliferation of A549 cells and the increasing protein level of LC3-II and Atg4.
      Blocking Atg4 expression by siRNA strongly reduced Beclin-1 and LC3-II protein
      expression and the number of autophagosome positive cells induced by Cd.
      Furthermore, Atg4 siRNA increased the number of cells at G0/G1 phase, reduced the
      number of S and G2/M phase cells, and inhibited Cd-induced cell growth
      significantly compared with that of Cd-treated Control siRNA cells. 3-MA
      pretreatment increased the percentage of G0/G1 phase cells, decreased S phase and
      G2/M phase percentage, and inhibited Cd-induced cell growth remarkably compared
      with that of only Cd-treated cells. Knocking down Atg4 reduced the number of
      cells that migrated and invaded through the Matrigel matrix significantly and led
      to a significant decrease of MMP-9 expression. In addition, in lung tissues of Cd
      treated BALB/c mice, the increased expression of LC3-II, Beclin-1 and Atg4 were
      observed. Taken together, our results demonstrated that ROS-dependent Atg4
      mediated autophagy plays an important role in Cd-induced cell growth, migration
      and invasion in A549 cells.

PMID- 29179952
TI  - Withering syndrome susceptibility of northeastern Pacific abalones: A complex
      relationship with phylogeny and thermal experience.
AB  - Population declines in wild and cultured abalones (Haliotis spp.) due to a
      bacterial disease called withering syndrome (WS) have been documented along the
      northeastern Pacific Ocean. However, observed differences in species
      susceptibility to the disease are not well understood. Here, we examined the
      susceptibility of three temperate abalone species, the cool water (4-14  degrees
      C) pinto or northern abalone (Haliotis kamtschatkana), the intermediate water (8
      18  degrees C) red abalone (H. rufescens), and the warm water (12-23  degrees C)
      pink abalone (H. corrugata), to experimental WS infection at temperatures
      facilitating disease proliferation. Mortality data paired with histological and
      molecular detection of the WS pathogen confirmed that these abalone species
      exhibit different levels of susceptibility to infection and resistance to WS
      development ranging from high susceptibility and low resistance in pinto abalone
      to moderate/low susceptibility and resistance in red and pink abalones. The
      temperature associated with WS induced mortalities also varied among species:
      pinto abalone died at the lowest experimental temperature (17.32 +/- 0.09 
      degrees C), while red abalone died at an intermediate temperature (17.96 +/- 0.16
      degrees C), and pink abalone required the highest temperature (18.84 +/- 0.16 
      degrees C). When data from the current and previous studies were examined,
      susceptibility to WS was inversely related to phylogenetic distance from white
      abalone (H. sorenseni), which had the highest susceptibility and lowest
      resistance of all abalone species tested prior to the current study. These
      results provide further evidence that an abalone's thermal optima and
      phylogenetic relationship can determine its susceptibility to WS; species with
      cool water evolutionary histories are most susceptible to WS and the most
      susceptible species appear to be closely related. Differences among the thermal
      ranges of abalone species have broad implications for WS disease dynamics and
      highlight the importance of understanding the mechanisms governing the abalone-WS
      relationship in order to properly manage declining abalone populations.

PMID- 29179953
TI  - Three-dimensional imaging and analysis of entire peripheral nerves after repair
      and reconstruction.
AB  - BACKGROUND: We wanted to achieve a three-dimensional (3D), non-destructive
      imaging and automatic post-analysis and evaluation of reconstructed peripheral
      nerves without involving cutting and staining processes. NEW METHOD: We used a
      laboratory-based micro computed tomography system for imaging, as well as a
      custom analysis protocol. The sample preparation was also adapted in order to
      achieve 3D images with true micrometer resolution and suitable contrast. RESULTS:
      Analysis of the acquired tomograms enabled the quantitative assessment of 3D
      tissue structures, i.e., surface morphology, nerve fascicles, nerve tissue
      volume, geometry, and vascular regrowth. The resulting data showed significant
      differences between operated animals and non-operated controls. COMPARISON WITH
      EXISTING METHODS: Our approach avoids the sampling error associated with
      conventional 2D visualization approaches and holds promise for automation of the
      analysis of large series of datasets. CONCLUSIONS: We have presented a potential
      way for 3D imaging and analysis of entire regenerated nerves non-destructively,
      paving the way for high-throughput analysis of therapeutic conditions of treating
      adult nerve injuries.

PMID- 29179955
TI  - The utility of bedside simulation for training in critical care obstetrics.
AB  - Over the last 2 decades, the maternal mortality ratio in the United States has
      doubled from 7.4/100,000 live births in 1986 to 14.5/100,000 today. Despite great
      advances in health care, increasing rates of maternal morbidity and mortality in
      the United States have prompted calls to action to reverse this disturbing trend.
      Assisted reproductive technology has allowed women to delay childbearing to more
      advanced ages, resulting in a greater number of pregnancies complicated by one or
      more of the diseases associated with aging, such as cardiovascular disease,
      cancer, type 2 diabetes, and hypertension. The obesity epidemic, increasing rates
      of chronic diseases affecting pregnancy, steadily rising cesarean delivery rate
      with resulting complications, and medical advances allowing women with rare, but
      serious diseases to conceive contribute to rising maternal morbidity and
      mortality rates. Obstetric critical care simulation training may result in
      improved multidisciplinary teamwork and patient outcomes; and fewer medical and
      communication errors.

PMID- 29179956
TI  - Extracorporeal membrane oxygenation (ECMO) during pregnancy and postpartum.
AB  - Extracorporeal membrane oxygenation (ECMO) can provide respiratory support (VV
      ECMO) or both respiratory and circulatory support (VA-ECMO). The use of ECMO has
      increased dramatically as a result of simpler technology. No level I evidence is
      yet available reflecting improved outcomes with ECMO. The use of this technology
      during pregnancy may be indicated in very select cases and should be delivered in
      centers with dedicated ECMO specialized units.

PMID- 29179957
TI  - Catastrophic antiphospholipid syndrome and pregnancy.
AB  - Catastrophic antiphospholipid syndrome (CAPS) is a rare but life-threatening
      condition that may be precipitated by pregnancy. The condition can be hard to
      diagnose since it mimics other thrombotic microangiopathies that are associated
      with pregnancy. Accurate and timely diagnosis is critical for effective
      treatment. In this review, we highlight pertinent clinical features of CAPS so
      that obstetricians will be able to recognize and treat the condition.

PMID- 29179954
TI  - Universal health coverage and intersectoral action for health: key messages from
      Disease Control Priorities, 3rd edition.
AB  - The World Bank is publishing nine volumes of Disease Control Priorities, 3rd
      edition (DCP3) between 2015 and 2018. Volume 9, Improving Health and Reducing
      Poverty, summarises the main messages from all the volumes and contains cross
      cutting analyses. This Review draws on all nine volumes to convey conclusions.
      The analysis in DCP3 is built around 21 essential packages that were developed in
      the nine volumes. Each essential package addresses the concerns of a major
      professional community (eg, child health or surgery) and contains a mix of
      intersectoral policies and health-sector interventions. 71 intersectoral
      prevention policies were identified in total, 29 of which are priorities for
      early introduction. Interventions within the health sector were grouped onto five
      platforms (population based, community level, health centre, first-level
      hospital, and referral hospital). DCP3 defines a model concept of essential
      universal health coverage (EUHC) with 218 interventions that provides a starting
      point for country-specific analysis of priorities. Assuming steady-state
      implementation by 2030, EUHC in lower-middle-income countries would reduce
      premature deaths by an estimated 4.2 million per year. Estimated total costs
      prove substantial: about 9.1% of (current) gross national income (GNI) in low
      income countries and 5.2% of GNI in lower-middle-income countries. Financing
      provision of continuing intervention against chronic conditions accounts for
      about half of estimated incremental costs. For lower-middle-income countries, the
      mortality reduction from implementing the EUHC can only reach about half the
      mortality reduction in non-communicable diseases called for by the Sustainable
      Development Goals. Full achievement will require increased investment or
      sustained intersectoral action, and actions by finance ministries to tax smoking
      and polluting emissions and to reduce or eliminate (often large) subsidies on
      fossil fuels appear of central importance. DCP3 is intended to be a model
      starting point for analyses at the country level, but country-specific cost
      structures, epidemiological needs, and national priorities will generally lead to
      definitions of EUHC that differ from country to country and from the model in
      this Review. DCP3 is particularly relevant as achievement of EUHC relies
      increasingly on greater domestic finance, with global developmental assistance in
      health focusing more on global public goods. In addition to assessing effects on
      mortality, DCP3 looked at outcomes of EUHC not encompassed by the disability
      adjusted life-year metric and related cost-effectiveness analyses. The other
      objectives included financial protection (potentially better provided upstream by
      keeping people out of the hospital rather than downstream by paying their
      hospital bills for them), stillbirths averted, palliative care, contraception,
      and child physical and intellectual growth. The first 1000 days after conception
      are highly important for child development, but the next 7000 days are likewise
      important and often neglected.

PMID- 29179958
TI  - [The tribulations of a chinese gentleman (of a chinese in China)].

PMID- 29179959
TI  - [The value of alpha-methylacyl-CoA racemase expression in the progression of
      colonic carcinoma].
AB  - Alpha-methylacyl-CoA racemase (AMACR) expression has been demonstrated in several
      normal tissues and in diverse types of carcinoma. Our aim was to analyze the
      immunohistochemical expression of AMACR in the sequence-progression of colonic
      cancer. We studied 237 cases, including samples of normal mucosa of the colon,
      adenomas with different degrees of dysplasia, colonic carcinomas, lymph nodes and
      liver metastases of colonic carcinomas. A scale of intensity and percentage of
      expression was used to analyze the AMACR immunohistochemical profile. The
      expression was nearly absent in samples of normal mucosa, increased in both
      adenomas and carcinomas, decreased in lymph node metastases but was significantly
      increased in liver metastases.

PMID- 29179960
TI  - [Integrated quality in clinical procedures: Experience from pathology departments
      in Chile].

PMID- 29179961
TI  - [Interconsultations: The added value of the pathologist].

PMID- 29179962
TI  - The spectrum of glomerular disease between the years 2003 and 2015 in Columbia: A
      review of 12,613 cases.
AB  - BACKGROUND: The prevalence of glomerular disease (GD) varies according to the
      different socio-demographic characteristics of each population. For the first
      time we present the prevalence of the different forms of GD among patients from
      several different areas of Columbia. METHODS: Data from 12,613 renal biopsies
      studied at our University Hospital between 2003 and 2015 was reviewed. Pathology
      results were classified according to a list of renal diseases proposed by various
      authors. RESULTS: Focal segmental glomerulosclerosis was present in 22%, IgA
      disease in 21%, Lupus nephritis in 17%, membranous glomerulonephritis in 13% and
      thin basal membrane disease in 9%. CONCLUSIONS: This study confirms that focal
      segmental glomerulosclerosis and IgA disease are the most prevalent GDs found in
      Columbian patients. This is the first study to analyze GDs in a Columbian
      population and we recommend that a national registry system be created to collect
      comprehensive information from future research.

PMID- 29179963
TI  - [Protocol for the study of bone tumours and standardization of pathology
      reports].
AB  - Primary bone neoplasms represent a rare and heterogeneous group of mesenchymal
      tumours. The prevalence of benign and malignant tumours varies; the latter
      (sarcomas) account for less than 0.2% of all malignant tumours. Primary bone
      neoplasms are usually diagnosed and classified according to the criteria
      established and published by the World Health Organization (WHO 2013). These
      criteria are a result of advances in molecular pathology, which complements the
      histopathological diagnosis. Bone tumours should be diagnosed and treated in
      referral centers by a multidisciplinary team including pathologists,
      radiologists, orthopedic surgeons and oncologists. We analyzed different national
      and international protocols in order to provide a guide of recommendations for
      the improvement of pathological evaluation and management of bone tumours. We
      include specific recommendations for the pre-analytical, analytical, and post
      analytical phases, as well as protocols for gross and microscopic pathology.

PMID- 29179964
TI  - A case of multifocal medulloblastoma in an adult patient.
AB  - Only five cases of multifocal medulloblastoma in the adult have been reported to
      date. We present a case in a male patient in his 50th decade of life who
      presented with three extra-axial lesions associated with a parenchymatous lesion
      of the right middle cerebellar peduncle. Sputum sample examination revealed
      larvae compatible with strongyloides stercoralis, which was our main differential
      diagnosis. Histological and immunohistochemical studies revealed the existence of
      a desmoplastic medulloblastoma.

PMID- 29179965
TI  - [Pseudomyogenic hemangioendothelioma in the upper limb: A case report and
      literature review].
AB  - Pseudomyogenic hemangioendothelioma, also called epithelioid sarcoma-like
      hemangioendothelioma, is a rare, vascular neoplasm usually with indolent
      behaviour. It was introduced in the latest World Health Organization (WHO)
      Classification of Tumours of Soft Tissue. We report a case of a 45 year-old
      patient presenting with a localized, palpable and slightly painful lesion in the
      left arm. Histologically it consisted of fascicles of spindle and epithelioid
      cells with ample eosinophilic cytoplasm, without nuclear pleomorphism or
      significant mitotic activity. Tumour cells showed diffuse expression for
      cytokeratin AE1/AE3, CD31 and FLI1, intact expression for INI1 and negativity for
      CD34. We describe the clinical, histological, molecular and immunohistochemical
      features of pseudomyogenic hemangioendothelioma and review the pertinent
      literature.

PMID- 29179966
TI  - Lymphoepithelioma-like carcinoma of the urinary bladder: A case report.
AB  - We report a case of lymphoepithelioma-like carcinoma of the urinary bladder in an
      elderly female patient. A 97-year old woman presented with hematuria, and an
      ultrasonographic urinary study showed a localized tumor in the trigone region of
      the urinary bladder. A transurethral resection revealed a mixed tumor formed by
      high-grade transitional carcinoma and lymphoepithelioma-like carcinoma that had
      infiltrated into the muscular propria. We describe the clinicopathological,
      morphological and immunohistochemical features of this tumor and briefly discuss
      its differential diagnosis and biological behavior.

PMID- 29179967
TI  - [From tumour to tumour: Metastasis of invasive ductal breast carcinoma to
      chromophobe renal cell carcinoma].
AB  - The coexistence of two or more tumours in the same patient is unusual, but even
      rarer is the metastasis of one tumour to another. Most reports are based on
      evidence from autopsies; very few refer to surgical specimens. The most common
      primary tumour is pulmonary carcinoma and most frequent metastatic tumour is
      renal clear cell carcinoma. We present the case of a 54 year-old female with a
      past history of infiltrating ductal carcinoma of the breast with metastases in
      lung, lymph nodes and bone. Three months previously to her referral to us, she
      had developed a renal mass and underwent nephrectomy. Histopathology revealed a
      renal chromophobe cell carcinoma with intratumoral breast cancer metastasis. We
      describe the histopathological, immunohistochemical and molecular features and
      review the recent literature.

PMID- 29179968
TI  - [Genetic analysis of a family with Von Hippel-Lindau syndrome].
AB  - Von Hippel-Lindau syndrome (VHL) is an autosomal dominant inherited disease
      associated with mutations in the VHL tumour suppressor gene located on chromosome
      3p25. VHL is characterized by the development of multiple malignant and benign
      tumours in the central nervous system and internal organs, including liver,
      pancreas and the adrenal gland. More than 823 different mutations of the VHL gene
      have currently been identified. In the present study we describe the case of a
      family affected by VHL treated at the University Hospital of La Ribera and the
      results of the genetic analysis of three relatives, identifying the mutation
      R167G in exon 3 of VHL gene as the cause of VHL syndrome in this family.

PMID- 29179970
TI  - An interproximal model to determine the erosion-protective effect of calcium
      silicate, sodium phosphate, fluoride formulations.
AB  - OBJECTIVES: Previous work has shown the effectiveness of a newly developed
      interproximal model to differentiate between the amount of remineralization
      caused by toothpastes used with or without a dual-phase gel treatment system
      containing calcium silicate, sodium phosphate salts and fluoride to repair acid
      softened enamel. The aim of this study was to utilize the same interproximal
      model to identify how effective calcium silicate phosphate toothpastes are at
      reducing surface softening in the early stages of erosion. The model was also
      used to identify the effect of increasing the frequency of acid exposure on the
      reduction in surface hardness. METHODS: Human enamel specimens were prepared and
      mounted in an interproximal face-to-face arrangement and exposed to a cycling
      regime of whole human saliva, treatment, artificial saliva and 1% citric acid pH
      3.75. Specimens were measured by surface microhardness at baseline and after
      three and seven days. The frequency of acid exposure was increased from 2 to 4
      cycles a day for the second part of the study. RESULTS: The results showed that
      specimens treated with the calcium silicate phosphate toothpastes softened less
      than those treated with control fluoridated or non-fluoride toothpastes at each
      time point and following an increase in the frequency of acid exposure.
      SIGNIFICANCE: This work has demonstrated how an interproximal model can also be
      successfully used to determine differences in the erosion protection of various
      treatments as well as determining how they perform when the frequency of acid
      exposure is increased.

PMID- 29179969
TI  - [Detection of herpes virus and human enterovirus in pathology samples using low
      density arrays].
AB  - Despite the frequency of infections with herpesviridae family, only eight
      subtypes affect humans (Herpex Simplex Virus types 1 and 2, Varicella Zoster
      Virus, Epstein-Barr Virus, Citomegalovirus and Human Herpes Virus types 6, 7 and
      8). Amongst enteroviruses infections, the most important are Poliovirus,
      Coxackievirus and Echovirus. Symptoms can vary from mild to severe and early
      diagnosis is of upmost importance. Nowadays, low-density arrays can detect
      different types of viruses in a single assay using DNA extracted from biological
      samples. We analyzed 70 samples of formalin-fixed and paraffin-embedded tissue,
      searching for viruses (HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, HHV-7 y HHV-8,
      Poliovirus, Echovirus and Coxsackievirus) using the kit CLART(r) ENTHERPEX. Out
      of the total of 70 samples, 29 were positive for viral infection (41.43%), and
      only 4 of them showed cytopathic effect (100% correlation between histology and
      the test). 47.6% of GVHD samples were positive for virus; 68.75% of IBD analyzed
      showed positivity for viral infection; in colitis with ulcers (neither GVHD nor
      IBD), the test was positive in 50% of the samples and was also positive in 50% of
      ischemic lesions. The high sensitivity of the technique makes it a useful tool
      for the pathologist in addition to conventional histology-based diagnosis, as a
      viral infection may affect treatment.

PMID- 29179971
TI  - Dentin bonding systems: From dentin collagen structure to bond preservation and
      clinical applications.
AB  - OBJECTIVES: Efforts towards achieving durable resin-dentin bonds have been made
      for decades, including the understanding of the mechanisms underlying hybrid
      layer (HL) degradation, manufacturing of improved adhesive systems, as well as
      developing strategies for the preservation of the HL. METHODS: This study
      critically discusses the available peer-reviewed research concerning the
      formation and preservation of the HL, the mechanisms that lead to the degradation
      of the HL as well as the strategies to prevent it. RESULTS: The degradation of
      the HL occurs through two main mechanisms: the enzymatic degradation of its
      collagen fibrils, and the leaching of the resin from the HL. They are enabled by
      residual unbound water between the denuded collagen fibrils, trapped at the
      bottom of the HL. Consequently, endogenous dentinal enzymes, such as the matrix
      metalloproteinases (MMPs) and cysteine cathepsins are activated and can degrade
      the denuded collagen matrix. Strategies for the preservation of the HL over time
      have been developed, and they entail the removal of the unbound water from the
      gaps between the collagen fibrils as well as different modes of silencing
      endogenous enzymatic activity. SIGNIFICANCE: Although there are many more hurdles
      to be crossed in the field of adhesive dentistry, impressive progress has been
      achieved so far, and the vast amount of available research on the topic is an
      indicator of the importance of this matter and of the great efforts of
      researchers and dental material companies to reach a new level in the quality and
      longevity of resin-dentin bonds.

PMID- 29179972
TI  - Cross-linking effect on dentin bond strength and MMPs activity.
AB  - OBJECTIVE: The objectives of the study were to evaluate the ability of a 1-ethyl
      3 (3-dimethylaminopropyl) carbodiimide (EDC)-containing primer to improve
      immediate bond strength of either self-etch or etch-and-rinse adhesive systems
      and to stabilize the adhesive interfaces over time. A further objective was to
      investigate the effect of EDC on the dentinal MMPs activity using zymographic
      analysis. METHODS: Freshly extracted molars (n=80, 20 for each group) were
      selected to conduct microtensile bond strength tests. The following groups were
      tested, immediately or after 1-year aging in artificial saliva: G1: Clearfil SE
      (CSE) primer applied on unetched dentin, pretreated with 0.3M EDC water-solution
      for 1min and bonded with CSE Bond; G2: as G1 but without EDC pre-treatment; G3:
      acid-etched (35% phosphoric-acid for 15s) dentin pretreated with 0.3M EDC, then
      bonded with XP Bond (XPB); Group 4 (G4): as G3 without EDC pre-treatment.
      Further, gelatinase activity in dentin powder treated with CSE and XPB with and
      without EDC pre-treatment, was analyzed using gelatin zymography. RESULTS: The
      use of 0.3M EDC-containing conditioner did not affect the immediate bond strength
      of XPB or CSE adhesive systems (p>0.05), while it improved the bond strength
      after 1year of aging (p<0.05). Pre-treatment with EDC followed by the application
      of CSE resulted in an incomplete MMPs inactivation, while EDC pretreatment
      followed by the application of XPB resulted in an almost complete inactivation of
      dentinal gelatinases. SIGNIFICANCE: The MUTBS and zymography results support the
      efficacy of EDC over time and reveal that changes within the dentin matrix
      promoted by EDC are not adhesive-system-dependent.

PMID- 29179973
TI  - Mechanism of bioactive molecular extraction from mineralized dentin by calcium
      hydroxide and tricalcium silicate cement.
AB  - OBJECTIVES: The objective of the present study was to elucidate the mechanism of
      bioactive molecule extraction from mineralized dentin by calcium hydroxide
      (Ca(OH)2) and tricalcium silicate cements (TSC). METHODS AND RESULTS:
      Transmission electron microscopy was used to provide evidence for collagen
      degradation in dentin surfaces covered with Ca(OH)2 or a set, hydrated TSC for 1
      3 months. A one micron thick collagen degradation zone was observed on the dentin
      surface. Fourier transform-infrared spectroscopy was used to identify increases
      in apatite/collagen ratio in dentin exposed to Ca(OH)2. Using three-point
      bending, dentin exposed to Ca(OH)2 exhibited significant reduction in flexural
      strength. Using size exclusion chromatography, it was found that the small size
      of the hydroxyl ions derived from Ca(OH)2 enabled those ions to infiltrate the
      intrafibrillar compartment of mineralized collagen and degrade the collagen
      fibrils without affecting the apatite minerals. Using ELISA, TGF-beta1 was found
      to be extracted from dentin covered with Ca(OH)2 for 3 months. Unlike acids that
      dissolve the mineral component of dentin to release bioactive molecules, alkaline
      materials such as Ca(OH)2 or TSC released growth factors such as TGF-beta1 via
      collagen degradation. SIGNIFICANCE: The bioactive molecule extraction capacities
      of Ca(OH)2 and TSC render these dental materials excellent for pulp capping and
      endodontic regeneration. These highly desirable properties, however, appear to be
      intertwined with the untoward effect of degradation of the collagen matrix within
      mineralized dentin, resulting in reduced flexural strength.

PMID- 29179974
TI  - Glycaemic responses in Asian and non-Asian people with type 2 diabetes initiating
      insulin glargine 100 units/mL: A patient-level pooled analysis of 16 randomised
      controlled trials.
AB  - AIMS: To compare outcomes between Asian and non-Asian patients with type 2
      diabetes (T2D) inadequately controlled on oral antidiabetic drugs (OADs)
      initiating insulin glargine 100 units (U)/mL (Gla-100) in randomised controlled
      clinical trials. METHODS: Post hoc analysis of patient-level data (Asian n = 235;
      non-Asian n = 3351) from 16 trials. RESULTS: At baseline, Asian patients were
      younger with lower body mass index (BMI), fasting C-peptide, and fasting plasma
      glucose (FPG) than non-Asian patients (all P < .001). Asian patients had a higher
      mean glycosylated haemoglobin (HbA1c) at Week 24 and less reduction in HbA1c from
      baseline (7.4% vs. 7.2%; -1.3% vs. -1.6%, respectively; P = .0001), and were less
      likely to achieve HbA1c <7.0% (40% vs. 47%; P = .002) than non-Asian patients.
      Reductions in FPG and rates of hypoglycaemia were similar between Asian and non
      Asian patients. Asian patients had less weight gain than non-Asian patients (+1.3
      vs. +1.9 kg, respectively, P = .013). CONCLUSIONS: In our post hoc meta-analysis,
      Gla-100 effectively lowers HbA1c and FPG in Asian patients with T2D uncontrolled
      on OADs with similar incidence of hypoglycaemia and less absolute weight gain
      compared with non-Asian patients. At a similar FPG reduction, fewer Asian
      patients achieved HbA1c target <7.0%, suggesting that prandial glucose needs to
      be addressed.

PMID- 29179975
TI  - Methicillin-resistant Staphylococcus aureus sequence type 45 with high rates of
      ciprofloxacin and tetracycline resistance in the residents and environments of
      long-term care facilities in Taiwan.

PMID- 29179976
TI  - Vitamin C prevents hypothyroidism associated neuronal damage in the hippocampus
      of neonatal and juvenile rats: A stereological study.
AB  - Hypothyroidism causes an imbalance in antioxidant and pro-oxidants criteria in
      the brain and enhances the concentration of reactive oxygen species (ROS), and
      neuronal damage has been observed following an excessive ROS. The main purpose of
      this study was to examine the preventive effect of vitamin C on hypothyroidism
      associated neuronal damage in the hippocampus of neonatal and juvenile rats.
      Pregnant rats after delivery of their pups were randomly divided into four groups
      and treated with (1) normal drinking water as a control group, (2)
      Propylthiouracil (PTU) 0.005% added to drinking water, (3-, 4) PTU + Vit C 10 mg/
      kg and PTU + Vit C 100 mg/ kg to drinking water. Treatment was carried out during
      rat's lactation period until to the postnatal day (PND) 60. To assess the
      histological and stereological changes that occur in this study, brains of 5 male
      pups were extracted. The number of dark neurons and apoptotic cells in the
      hippocampal sub-regions of PTU group was significantly greater than the control
      group's hippocampal sub-regions. In addition, hypothyroidism induced a reduction
      in the hippocampal volume and increased the numerical density and the total
      amount of dark neurons. The vitamin C only dose of 100 mg/kg significantly
      reduced the number of dark neurons and apoptotic cells (P < 0.01) and
      considerably weakened the influence of hypothyroidism on the volume reduction of
      the hippocampus (P < 0.05). The current study suggested that vitamin C
      administration has a possibility to prevent hippocampal neuronal damage caused by
      neonatal and juvenile hypothyroidism in rats.

PMID- 29179977
TI  - Altered O-glycosylation is associated with inherent radioresistance and
      malignancy of human laryngeal carcinoma.
AB  - Radioresistance (inherent or acquired) remains a major obstacle affecting the
      clinical outcome of radiotherapy for laryngeal carcinoma. Results from our
      laboratory and other groups suggest that aberrant glycosylation contributes to
      cancer acquired radioresistance. However, the role of glycosylation in inherent
      radioresistance of laryngeal carcinoma has not been fully uncovered. In this
      study, we investigated the glycan profiling of the inherent radioresistant (Hep
      2max) and radiosensitive (Hep-2min) cell lines using lectin microarray analysis.
      The results revealed that the radioresistant cell line Hep-2max presented higher
      core 1-type O-glycans than the sensitive one. Further analysis of the O-glycan
      regulation by benzyl-alpha-GalNAc application in Hep-2max cells showed partial
      inhibition of the O-glycan biosynthesis and increased radiosensitivity. In
      addition, core 1 beta1, 3-galactosyltransferase (C1GALT1) overexpression in Hep
      2min cells enhanced cell migration, invasion, and radioresistance. Conversely,
      knockdown of C1GALT1 in Hep-2max cells was able to suppress these malignant
      phenotypes. Moreover, mechanistic investigations showed that C1GALT1 modified the
      O-glycans on integrin beta1 and regulated its activity. The glycosylation
      mediated radioresistance was further inhibited by anti-integrin beta1 blocking
      antibody. Importantly, we also observed that core 1-type O-glycans expression was
      correlated with advanced tumor stage, metastasis, and poor survival of laryngeal
      carcinoma patients. These findings suggest that altered O-glycosylation can lead
      to the inherent radioresistance and progression, and therefore may be important
      for enhancing the efficacy of radiotherapy in laryngeal carcinoma.

PMID- 29179978
TI  - Assessment of the extent of pituitary macroadenomas resection in immediate
      postoperative MRI.
AB  - OBJECTIVE: To evaluate if it is possible to determine the extent of pituitary
      macroadenomas resection in the immediate postoperative pituitary magnetic
      resonance imaging (MRI). MATERIAL AND METHODS: MRI of patient with pituitary
      macroadenomas from January 2010 until October 2014 were reviewed. Those patients
      who had diagnostic MRI, immediate post-surgical MRI and at least one MRI control
      were included. We evaluate if the findings between the immediate postsurgical MRI
      and the subsequent MRI were concordant. Cases which didn't have evolutionary
      controls and those who were reoperation for recurrence were excluded. The degree
      of tumor resection was divided into groups: total resection, partial resection
      and doubtful. All MRI studies were performed on a1.5T machine following the same
      protocol sequences for all cases. One morphological part, a dynamic contrast iv
      and late contrast part. RESULTS: Of the 73 cases included, immediate
      postoperative pituitary MRI was interpreted as total resection in 38 cases and
      tumoral rest in 28 cases, uncertainty among rest or inflammatory changes in 7
      cases. Follow- up MRI identified 41 cases total resection and tumoral rest in 32.
      Sensitivity and specificity of 0.78 and 0.82 and positive and negative predictive
      value (PPV and NPV) 0.89 and 0.89 respectively were calculated. CONCLUSION:
      Immediate post-surgery pituitary MRI is useful for assessing the degree of tumor
      resection and is a good predictor of the final degree of real resection compared
      with the following MRI studies. It allows us to decide the most appropriate
      treatment at an early stage.

PMID- 29179979
TI  - Recurrence of oral mucocoeles in adolescents after excision.

PMID- 29179980
TI  - Dimensions of hard and soft tissue around adjacent, compared with single-tooth,
      zirconia implants.
AB  - Preservation or regeneration of the papilla has always been a challenge around
      consecutive implants or with implants next to teeth, and many studies have
      evaluated the papilla's behaviour and patterns based on surgical technique and
      prosthetic design, though evidence about its behaviour around zirconia implants
      is scarce. The aim of this study was to evaluate papilla behaviour between
      implants and teeth (tooth-implant group) and between consecutive implants
      (implant-implant group). Ninety patients with 122 zirconia implants (Straumann(r)
      PURE Ceramic Implant) were examined at the one-year follow up. We measured the
      effect of the distance: first from the base of the contact point of the crowns to
      the contact with bone at the implant site (D1); secondly, to the contact with the
      bone at the neighbouring tooth or implant site (D2); and thirdly on the papillary
      deficit (D3). In both the tooth-implant group and the implant-implant group, D1
      and D2 correlated significantly with the papillary deficit (D3), whereas D2 was
      the major determinant factor (Spearman's rho=0.60). In both groups, when D1 and
      D2 were <6mm, the papilla was present every time. The papillary deficit was
      significantly greater in the tooth-implant group than in the implant-implant
      group (p=0.048). We conclude that the ideal distance from the base of the contact
      point to the bone contact at the implant and to the bone contact at the adjacent
      tooth in both groups is <6mm. The height of the bone on the teeth adjacent to
      implants has a significant impact on that of the papilla.

PMID- 29179981
TI  - Choice of treatment in Clostridium difficile-associated diarrhoea: Clinical
      practice guidelines or risk classifications.

PMID- 29179982
TI  - Paediatric invasive pneumococcal disease on the island of Gran Canaria: 16-year
      prospective study (2001-2016).
AB  - OBJECTIVES: To calculate the incidence of invasive pneumococcal disease (IPD) in
      the paediatric population of Gran Canaria (Spain), its clinical and
      epidemiological characteristics, serotype distribution, antibiotic resistance,
      and variations in these variables before and after the introduction of the PCV13
      vaccine. METHODS: Prospective hospital-based study including all patients (190)
      aged 0-14 years admitted with confirmed IPD between January 2001-May 2010 (152
      cases) and June 2010-December 2016 (38 cases). Patients were divided into 3 age
      groups (<2 years; 2-5 years; and >5 years). Clinical symptoms were mutually
      exclusively classified as meningitis, bacteraemic pneumonia, pleural effusion
      (PE), empyema or bacteraemia without a focus. RESULTS: Most cases occurred in
      boys (59.47%), during autumn-winter (65.79%), in children aged <2 years (55.79%)
      and with mean age increasing from the pre-PCV13 to the post-PCV13 period (2.5 vs
      3.1 years). Incidence between periods reduced by 66.4% (p<0.001): from
      13.1/100,000 to 4.4/100,000. PEs (3.9% vs 18.4%, p<0.005) and empyemas (1.5% vs
      16.7%, p=NS) increased in the post-PCV13 period whereas all other symptoms
      decreased, although this was not statistically significant. Vaccine serotypes
      (77% vs 40.6%, p=0.000), particularly serotypes 19A (23.9% vs 12.5%) and 14
      (14.2% vs 9.4%), as well as erythromycin resistance (57.2% vs 7.9%, p=0.000)
      decreased in the post-PCV13 period. CONCLUSION: IPD incidence, vaccine serotypes
      and erythromycin resistance decreased in the post-PCV13 period whereas PEs
      increased.

PMID- 29179983
TI  - Abdominal violaceous skin lesions of a 47-year-old woman following a geometric
      pattern.

PMID- 29179984
TI  - Prevalence of antibodies and humoral response after seasonal trivalent
      vaccination against influenza B lineages in an elderly population of Spain.
AB  - INTRODUCTION: The aim of this study was to analyze the presence of antibodies
      against both Yamagata and Victoria influenza B lineages and to check the response
      after seasonal trivalent vaccination. MATERIALS AND METHODS: Haemagglutination
      inhibition assays were performed with pre-and post-vaccination serum samples from
      174 individuals >=65 years of age vaccinated with seasonal trivalent influenza
      vaccines during the 2006-2007, 2008-2009, 2009-2010 and 2010-2011 vaccine
      campaigns. RESULTS: 33.9% of individuals showed pre-vaccine protective antibodies
      (>=1/40) against B/Yamagata lineage and 41.4% against B/Victoria lineage. The
      annual trivalent vaccine induced significant homologous seroconversion in 14
      35.6% of individuals in each vaccine campaign. CONCLUSIONS: The population >=65
      years has low-moderate seroprotection against B influenza lineages. Trivalent
      vaccination induced a slight increase of seroprotection. The trivalent vaccine
      should be administered to all individuals >=65 years in all vaccine campaigns.

PMID- 29179985
TI  - Cardiac CD68+ and stabilin-1+ macrophages in wound healing following myocardial
      infarction: From experiment to clinic.
AB  - Myocardial infarction (MI) remains the leading cause of mortality and morbidity
      throughout the world. Macrophages are key innate immune cells that play a
      significant role in transition from the inflammatory to the regenerative phase
      during wound healing following MI. The scavenger receptor stabilin-1 is one of
      the most interesting macrophage biomarkers. This receptor contributes to wound
      healing, angiogenesis, and tissue remodeling. We suggested a research protocol
      using macrophage biomarkers to study the cellular basis of cardiac remodeling and
      healing in patients with acute MI. The purpose of the research was to translate
      experimental knowledge regarding macrophage subsets and their biomarkers in post
      infarction myocardial regeneration into results observed in clinical settings.
      The study included 41 patients with fatal MI type 1. All patients were divided
      into four groups according to the timeline of MI histopathology. In addition to
      routine histopathological analysis, macrophage infiltration was assessed by
      immunohistochemistry. We used CD68 as a marker for the cells of the macrophage
      lineage and stabilin-1 as an M2-like macrophage biomarker. The number of CD68+
      and stabilin-1+ macrophages in the infarct area increased and peaked in the
      regenerative phase and did not decrease in the late stage of MI. In the peri
      infarct area, the number of CD68+ macrophages increased in the inflammatory
      phase, peaked during the reparative phase, and did not decrease in the late
      phase, while the number of stabilin-1+ macrophages increased in the regenerative
      phase and remained unchanged. Additionally, in the reparative phase, we observed
      increase in the number of CD68+ and stabilin-1+ macrophages in the non-infarct
      area. The research protocol suggested allowed us to translate experimental
      knowledge regarding macrophage subsets and their biomarkers in post-infarction
      myocardial regeneration into clinical data. Taken together, these results
      demonstrated biphasic cardiac macrophage response following acute MI somewhat
      similar to that in a murine model. The increase in stabilin-1+ macrophage
      infiltration noticed in the myocardium during the regenerative phase and the
      strong positive correlation between the number of these cells and timeline of MI
      histopathology enabled us to propose stabilin-1 as a diagnostic macrophage
      biomarker in myocardium wound healing in patients with acute MI.

PMID- 29179986
TI  - Natural killer cell metabolism.
AB  - Natural killer (NK) cells are a critical component in the innate immune response
      against disease. NK cell function is tightly regulated by specific cytokine and
      activation/inhibitory receptor signalling, leading to diverse effector responses.
      Like all living cells, energy metabolism is a fundamental requirement for NK cell
      activation and survival. There is growing evidence that distinct functional
      profiles of NK cells are determined by alterations to cellular metabolic
      pathways. In this review, we summarise current literature that has explored NK
      cell metabolism to provide insight into how metabolic regulation controls NK cell
      function. We focus on metabolism pathways induced by different NK cell stimuli,
      metabolic regulatory proteins, and nutrient and hormonal levels in health and
      disease which impact on NK cell metabolic and functional activity.

PMID- 29179987
TI  - Identification of genes involved in the four stages of colorectal cancer: Gene
      expression profiling.
AB  - BACKGROUND: Colorectal cancer (CRC) is a common cancer with high morbidity and
      mortality. However, its molecular mechanism is not clear, nor the genes related
      to CRC stages. METHODS: Gene expression data in CRC and healthy colorectal
      tissues were obtained from gene expression omnibus. Limma package was used to
      identify the differentially expressed genes (DEGs) between control and CRC (stage
      I, II, III, and IV), obtaining 4 DEG sets. VennPlex was utilized to find all DEGs
      and intersection DEGs. Functional interactions between all DEGs and protein
      protein interactions (PPIs) between intersection DEGs were analyzed using
      ReactomeFIViz and STRING, respectively, and networks were visualized. Known CRC
      related genes were down-loaded from Comparative Toxicogenomics Database and
      mapped to PPI network. RESULTS: Totally, 851, 760, 729, and 878 DEGs were found
      between control and CRC stage I, II, III, and IV, respectively. Taken together,
      1235 DEGs were found, as well as 128 up-regulated intersection DEGs, 365 down
      regulated intersection DEGs, and 0 contra-regulated DEG. A functional interaction
      network of all DEGs and a PPI network of intersection DEGs were constructed, in
      which CDC20, PTTG1, and MAD2L1 interacted with BUB1B; UGT2B17 interacted with
      ADH1B; MCM7 interacted with MCM2. BUB1B, ADH1B, and MCM2 were known CRC-related
      genes. Gradually upregulated expressions of CDC20, PTTG1, MAD2L1, UGT2B17, and
      MCM7 in stage I, II, III, and IV CRC were confirmed by using quantitative PCR.
      Besides, up-regulated intersection DEGs enriched in pathways about Cell cycle,
      DNA replication, and p53 signaling. CONCLUSION: CDC20, PTTG1, MAD2L1, UGT2B17,
      and MCM7 might be CRC stage-related genes.

PMID- 29179988
TI  - Label-free monitoring of ambient oxygenation and redox conditions using the
      photodynamics of flavin compounds and transient state (TRAST) spectroscopy.
AB  - Transient state (TRAST) monitoring can determine population dynamics of long
      lived, dark transient states of fluorescent molecules, detecting only the average
      fluorescence intensity from a sample, when subject to different excitation pulse
      trains. Like Fluorescence Correlation Spectroscopy (FCS), TRAST unites the
      detection sensitivity of fluorescence with the environmental sensitivity of long
      lived non-fluorescent states, but does not rely on detection of stochastic
      fluorescence fluctuations from individual molecules. Relaxed requirements on
      noise suppression, detection quantum yield and time-resolution of the instrument,
      as well as on fluorescence brightness of the molecules studied, make TRAST
      broadly applicable, opening also for investigations based on less bright, auto
      fluorescent molecules. In this work, we applied TRAST to study the transient
      state population dynamics within the auto-fluorescent coenzymes flavin adenine
      dinucleotide (FAD) and flavin-mononucleotide (FMN). From the experimental TRAST
      data, we defined state models, and determined rate parameters for triplet state
      and redox transitions within FMN and FAD, stacking and un-stacking rates of
      external redox active quenching agents and by the adenine moiety of FAD itself.
      TRAST experiments were found to be well capable to resolve these transitions in
      FMN and FAD, and to track how the transitions are influenced by ambient
      oxygenation and redox conditions. This work demonstrates that TRAST provides a
      useful tool to follow local oxygenation and redox conditions via FMN and FAD
      fluorescence, and forms the basis for measurements on flavo-proteins and of redox
      and metabolic conditions in more complex environments, such as in live cells.

PMID- 29179989
TI  - Examination of biochemical and biological activities of Bothrops jararaca
      (Serpentes: Viperidae; Wied-Neuwied 1824) snake venom after up to 54 years of
      storage.
AB  - The number of snakes donated to the Brazilian Instituto Butantan has been
      decreasing in the past 10 years. This circumstance motivated us to compare the
      properties of five venom pools of Bothrops jararaca snake stored for up to 54
      years. Results showed differences among venom pools regarding enzymatic and other
      biological activities, such as caseinolytic, phospholipase A2, hemorrhagic and
      coagulant activities, as well as antigenicity. Protein content, reverse-phase
      chromatographic profile, and immunorecognition by commercial Bothrops antivenom
      were comparable for all venom pools, although lethality of the most recent
      preparations was higher. Since the lowest functional activities did not always
      correspond to older venoms, differences among venom pools used for antivenom
      production during the period 1963-2008 may correlate with the different
      proportions of venoms from different localities used in their generation, rather
      than to long-term storage. We conclude that B. jararaca venoms properly stored
      for long periods of time retain their structural and pharmacological activities,
      thus representing useful materials for scientific research and antivenom
      production.

PMID- 29179990
TI  - Snakebite by Micrurus averyi (Schmidt, 1939) in the Brazilian Amazon basin: Case
      report.
AB  - Micrurus snakes, commonly known as coral snakes, are responsible for 0.4% of the
      snakebites envenomings in Brazil. In this report, we describe a case of
      envenoming by Micrurus averyi, the black-headed coral snake, recorded in the
      western Brazilian Amazon. To the best of our knowledge, this is the first
      published case perpetrated by this species. The major complaint of the patient
      was an intense local pain and paresthesia. Examination of the bite site revealed
      edema extending from the left foot up the left leg that was accompanied by
      erythema involving the foot and distal third of the leg. Systemic signs at
      admission included nausea and drooling. The patient was treated with 100 mL of
      coral snake antivenom and intravenous analgesics (dipyrone) and was discharged 48
      h post-admission with no complaints. The patient showed more intense local edema
      than that generally described in several other cases of Micrurus bites in Brazil.

PMID- 29179991
TI  - The North American Society of Toxinology establishes formal affiliation with
      Toxicon.

PMID- 29179992
TI  - Detection of a novel mutation conferring acyclovir resistance and consecutive
      treatment failure in an HIV-positive patient with recurrent HSV-2 infection.

PMID- 29179993
TI  - Dissociable effects of reward and expectancy during evaluative feedback
      processing revealed by topographic ERP mapping analysis.
AB  - Evaluative feedback provided during performance monitoring (PM) elicits either a
      positive or negative deflection ~250-300ms after its onset in the event-related
      potential (ERP) depending on whether the outcome is reward-related or not, as
      well as expected or not. However, it remains currently unclear whether these two
      deflections reflect a unitary process, or rather dissociable effects arising from
      non-overlapping brain networks. To address this question, we recorded 64-channel
      EEG in healthy adult participants performing a standard gambling task where
      valence and expectancy were manipulated in a factorial design. We analyzed the
      feedback-locked ERP data using a conventional ERP analysis, as well as an
      advanced topographic ERP mapping analysis supplemented with distributed source
      localization. Results reveal two main topographies showing opposing valence
      effects, and being differently modulated by expectancy. The first one was short
      lived and sensitive to no-reward irrespective of expectancy. Source-estimation
      associated with this topographic map comprised mainly regions of the dorsal
      anterior cingulate cortex. The second one was primarily driven by reward, had a
      prolonged time-course and was monotonically influenced by expectancy. Moreover,
      this reward-related topographical map was best accounted for by intracranial
      generators estimated in the posterior cingulate cortex. These new findings
      suggest the existence of dissociable brain systems depending on feedback valence
      and expectancy. More generally, they inform about the added value of using
      topographic ERP mapping methods, besides conventional ERP measurements, to
      characterize qualitative changes occurring in the spatio-temporal dynamic of
      reward processing during PM.

PMID- 29179994
TI  - Management of myocardial dysfunction in septic shock. Potential role of
      extracorporeal membrane oxygenation.

PMID- 29179996
TI  - Combined effect of gestational stress and postpartum stress on maternal care in
      rats.
AB  - Variations in maternal care in the rat influence the development of individual
      differences in behavioral and endocrine responses to stress. This study aimed to
      examine the interaction between intragastric intubation during late gestation and
      postpartum stress, induced by pup separation, on maternal behavior and on dams'
      emotional state and HPA axis function. Rats received intragastric intubation of
      water on days 12-20 of gestation or remained untreated in their home cage (naive
      dams). Pup separation was used as a model of postpartum stress. The procedure
      consisted of a daily separation of the dam from its litter for 3h from PND 3
      until PND 15. Pup separation was carried out in both naive and intubated dams.
      The behavioral results indicate that the association of these two stressors
      significantly decreased arched-back nursing (ABN) and licking and grooming (LG),
      behaviors considered important parameters to discriminate the high quality of
      maternal care. Moreover, dams that received both stressors displayed less nest
      building and blanket nursing behaviors; no effect on the frequency of passive and
      total nursing was recorded. The analysis of single effects on ABN and LG,
      revealed that dams that underwent gestational stress induced by intragastric
      intubation displayed less LG, but ABN was overall unchanged. On the contrary, pup
      separation stress significantly increased ABN and LG upon reunion of naive dams
      with their pups. Treatments per se or the association of both induced modest
      changes in plasma levels of allopregnanolone and corticosterone that likely did
      not influence maternal care. These data show that the association of a mild
      stress during gestation with an unfavorable experience after parturition had a
      significant impact on maternal care. This effect seems independent from HPA axis
      activation or from changes in emotional state; further studies would be necessary
      to ascertain the neural changes that could contribute to altered maternal
      behavior in stressed mothers. Moreover, these results suggest that the use of
      intragastric intubation during gestation would interfere with measures of drug
      induced changes in maternal behavior and likely their consequences on the
      offspring.

PMID- 29179995
TI  - Non-bilayer structures in mitochondrial membranes regulate ATP synthase activity.
AB  - Cardiolipin (CL) is an anionic phospholipid at the inner mitochondrial membrane
      (IMM) that facilitates the formation of transient non-bilayer (non-lamellar)
      structures to maintain mitochondrial integrity. CL modulates mitochondrial
      functions including ATP synthesis. However, the biophysical mechanisms by which
      CL generates non-lamellar structures and the extent to which these structures
      contribute to ATP synthesis remain unknown. We hypothesized that CL and ATP
      synthase facilitate the formation of non-bilayer structures at the IMM to
      stimulate ATP synthesis. By using 1H NMR and 31P NMR techniques, we observed that
      increasing the temperature (8 degrees C to 37 degrees C), lowering the pH (3.0),
      or incubating intact mitochondria with CTII - an IMM-targeted toxin that
      increases the formation of immobilized non-bilayer structures - elevated the
      formation of non-bilayer structures to stimulate ATP synthesis. The F0 sector of
      the ATP synthase complex can facilitate the formation of non-bilayer structures
      as incubating model membranes enriched with IMM-specific phospholipids with
      exogenous DCCD-binding protein of the F0 sector (DCCD-BPF) elevated the formation
      of immobilized non-bilayer structures to a similar manner as CTII. Native PAGE
      assays revealed that CL, but not other anionic phospholipids, specifically binds
      to DCCD-BPF to promote the formation of stable lipid-protein complexes.
      Mechanistically, molecular docking studies identified two lipid binding sites for
      CL in DCCD-BPF. We propose a new model of ATP synthase regulation in which CL
      mediates the formation of non-bilayer structures that serve to cluster protons
      and ATP synthase complexes as a mechanism to enhance proton translocation to the
      F0 sector, and thereby increase ATP synthesis.

PMID- 29179997
TI  - Elevated cyclic AMP levels promote BRAFCA/Pten-/- mouse melanoma growth but pCREB
      is negatively correlated with human melanoma progression.
AB  - Melanocyte development and differentiation are regulated by cAMP, which is
      produced by the adenylate cyclase (AC) enzyme upon activation of the melanocortin
      1-receptor (MC1R). Individuals carrying single amino acid substitution variants
      of MC1R have impaired cAMP signaling and higher risk of melanoma. However, the
      contribution of AC to this risk is not clear. Downstream of AC, the
      phosphorylated transcription factor, cyclic AMP Responsive Element Binding
      Protein (pCREB), which is activated by protein kinase A, regulates the expression
      of several genes including the melanocyte master regulator MITF. The roles of AC
      and CREB in melanoma development and growth are not well understood. Here, we
      investigated the effect of topical application of AC inhibitor on BrafCA/Pten-/-
      mouse melanoma development. We show that AC inhibitor delays melanoma growth
      independent of MAPK pathway activity and melanin content. Next, employing a
      primary melanoma tissue microarray and quantitative immunohistochemistry, we show
      that pCREB levels are positively correlated with the proliferative status of
      melanoma, but low pCREB expression is associated with tumor aggressiveness and
      metastatic recurrence. These data suggest that low cAMP signaling inhibits tumor
      growth but is a predictor of melanoma aggressiveness.

PMID- 29179999
TI  - Phytochemicals as inhibitors of NF-kappaB for treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia. The exact
      pathophysiology of this disease remains incompletely understood and safe and
      effective therapies are required. AD is highly correlated with neuroinflammation
      and oxidative stress in brain causing neuronal loss. Nuclear factor of activated
      B-cells (NF-kappaB) is involved in physiological inflammatory processes and thus
      representing a promising target for inflammation-based AD therapy. Phytochemicals
      are able to interfere with the NF-kappaB pathway. They inhibit the
      phosphorylation or the ubiquitination of signaling molecules, and thus, inhibit
      the degradation of IkappaB. The translocation of NF-kappaB to the nucleus and
      subsequent transcription of pro-inflammatory cytokines are inhibited by the
      actions of phytochemicals. Additionally, natural compounds preventing the
      interaction of NF-kappaB can block NF-kappaB's transcriptional activity by
      inhibiting its binding to target DNA. Many polyphenols including curcumin,
      resveratrol, pterostilbene, punicalagin, macranthoin G, salidroside, 4-O
      methylhonokiol, lycopene, genistein, obovatol and gallic acid were reported as
      potent NF-kappaB inhibitors for AD treatment. Several alkaloids such as
      galantamine, glaucocalyxin B, tetrandrine, berberine, oridonin, anatabine have
      been shown anti-inflammatory effects in AD models in vitro as well as in vivo.
      Besides, vitamins, tanshinone IIA, artemisinin, dihydroasparagusic acid,
      geniposide, xanthoceraside, l-theranine, 1,8-cineole and paeoniflorin were
      described as promising NF-kappaB inhibitors. In conclusion, natural products from
      plants represent interesting candidates for AD treatment. They may qualify as
      promising compounds for the development of derivatives providing enhanced
      pharmacological features.

PMID- 29179998
TI  - ELL2 regulates DNA non-homologous end joining (NHEJ) repair in prostate cancer
      cells.
AB  - ELL2 is an androgen-responsive gene that is expressed by prostate epithelial
      cells and is frequently down-regulated in prostate cancer. Deletion of Ell2 in
      the murine prostate induced murine prostatic intraepithelial neoplasia and ELL2
      knockdown enhanced proliferation and migration in C4-2 prostate cancer cells.
      Here, knockdown of ELL2 sensitized prostate cancer cells to DNA damage and
      overexpression of ELL2 protected prostate cancer cells from DNA damage. Knockdown
      of ELL2 impaired non-homologous end joining repair but not homologous
      recombination repair. Transfected ELL2 co-immunoprecipitated with both Ku70 and
      Ku80 proteins. ELL2 could bind to and co-accumulate with Ku70/Ku80 proteins at
      sites of DNA damage. Knockdown of ELL2 dramatically inhibited Ku70 and Ku80
      recruitment and retention at DNA double-strand break sites in prostate cancer
      cells. The impaired recruitment of Ku70 and Ku80 proteins to DNA damage sites
      upon ELL2 knockdown was rescued by re-expression of an ELL2 transgene insensitive
      to siELL2. This study suggests that ELL2 is required for efficient NHEJ repair
      via Ku70/Ku80 in prostate cancer cells.

PMID- 29180000
TI  - Usefulness of biochemical remission and transient elastography in monitoring
      disease course in autoimmune hepatitis.
AB  - BACKGROUND & AIMS: Liver fibrosis regression but also progression may occur in
      patients with autoimmune hepatitis (AIH) under treatment. There is a need for non
      invasive surrogate markers for fibrosis development in AIH to better guide
      immunosuppressive treatment. The aims of the study were to assess the impact of
      complete biochemical remission defined as normalisation of aminotransferases and
      IgG on histological activity and fibrosis development, and the value of repeat
      transient elastography (TE) measurement for monitoring disease progression in
      AIH. METHODS: A total of 131 liver biopsies from 60 patients with AIH and more
      than 900 TE from 125 patients with AIH, 130 with primary biliary cholangitis
      (PBC) and 100 with primary sclerosing cholangitis (PSC), were evaluated. Time
      intervals between TE were at least 12 months. Patients with AIH were treated for
      at least six months at first TE. RESULTS: In contrast to PBC and PSC, a decrease
      of liver stiffness (LS) was observed in the whole group of patients with AIH (
      6.2%/year; 95% CI -12.6% to -0.2%; p = 0.04). The largest decrease of LS was
      observed in patients with severe fibrosis at baseline (F4: -11.7%/year; 95% CI 
      19% to -3.5%; p = 0.006). Complete biochemical remission was strongly linked to
      regression of LS ("remission": -7.5%/year vs. "no remission": +1.7%/year, p
      <0.001). Similarly, complete biochemical remission predicted low histological
      disease activity and was the only independent predictor for histological fibrosis
      regression (relative risk3.66; 95% CI1.54-10.2; p = 0.001). Patients with F3/F4
      fibrosis, who remained in biochemical remission showed a considerable decrease of
      fibrosis stage (3.7 +/- 0.5 to 1.8 +/- 1.7; p = 0.007) on histological follow-up.
      CONCLUSIONS: This study demonstrates that complete biochemical remission is a
      reliable predictor of a good prognosis in AIH and leads to fibrosis regression
      that can be monitored by TE. LAY SUMMARY: Autoimmune hepatitis is an inflammatory
      disease of the liver, which often progresses to cirrhosis if left untreated or in
      the case of insufficient treatment response. Current guidelines have defined
      biochemical remission (normalisation of biochemical markers for liver
      inflammation) as a major goal in the treatment of AIH. However, data on the
      prognostic relevance of this definition are scarce. Herein, we demonstrate that
      the current definition of biochemical remission is a reliable surrogate for low
      disease activity on histological assessment and for a beneficial long-term
      disease course. In addition, we establish transient elastography, a non-invasive
      ultrasound-based method of measuring scarring of liver tissue, as a reliable tool
      to monitor disease course in AIH.

PMID- 29180001
TI  - Effect of the FE2+ chelation by 2,2'-dipyridyl in the doxorubicin-induced
      lethality in breast tumor cell lines.
AB  - Breast cancer cells may exhibit changes in iron homeostasis, which results in
      increased labile iron pool (LIP) levels. Several studies highlight the crucial
      role of high LIP levels in the maintenance of tumor cell physiology. Iron
      chelators have been tested in anticancer therapy in combination with
      chemotherapeutic agents, to improve drug efficacy. Thus, the aim of this study
      was to evaluate the effect of 2,2'-dipyridyl (DIP), a Fe2+ chelator, in
      combination with doxorubicin (DOX) in breast tumor cells. The maximum
      concentration of DIP that did not significantly reduce the viability of MDA-MB
      231 cells was 10MUM and for MCF-7 cells was 50MUM. We observed that MCF-7 had
      higher LIP levels than MDA-MB-231 cells. DIP alone increased ROS generation in
      MCF-7 cells, and DIP pretreatment reduced ROS generation induced by DOX
      treatment. In conclusion, the increase in MCF-7 cell viability induced by DIP
      pretreatment in DOX-treated cells seems to be related to an increase in the
      cellular antioxidant capacity and the iron chelator did not improve drug efficacy
      in the two breast tumor cell lines analyzed.

PMID- 29180003
TI  - Correlations of hair level with salivary level in cortisol and cortisone.
AB  - AIMS: Contrary findings exist on the consistency between hair cortisol and
      salivary cortisol in assessing the basal activity of the hypothalamic-pituitary
      adrenal (HPA) axis. The mismatches in temporal characteristic and the indices of
      hair and salivary cortisol might be potential reasons for the inconsistency. The
      aim of this study was to investigate the consistency between hair and salivary
      levels in cortisol and cortisone by directly examining the correlation between
      hair level and salivary level with different temporal characteristics (acute,
      short-term and long-term levels) and reflecting different HPA functions (basal
      level and reactivity level) in the well-matched time span. MAIN METHODS: A
      longitudinal design within a five-week period was conducted in a sample of 44
      healthy female college students (mean age: 18.8yrs.; age range: 18-22yrs) of Han
      nationality with the exclusion criteria, such as use of oral contraceptives or
      glucocorticoids and bleached hairs, etc. Four saliva samples (awakening,
      awakening+30min, awakening+4h and awakening+9h) were collected from an identical
      participant on three separate days with an interval of one week and 1-cm hair
      segment nearest to the scalp was collected two weeks later after completing
      saliva collection. Cortisol and cortisone in saliva and hair were simultaneously
      measured with high performance liquid chromatography tandem mass spectrometry.
      KEY FINDINGS: There were significantly moderate correlations in cortisol and
      cortisone between hair level and three-day average of single-day salivary level,
      but low to moderate correlations between hair level and single-point and single
      day salivary level. Hair cortisol and cortisone were unrelated to single-day
      level and three-day average of diurnal slope and cortisol awakening response of
      salivary cortisol and cortisone, respectively. SIGNIFICANCE: The considerable
      consistency between hair level and long-term salivary level in cortisol and
      cortisone implies that cortisol and cortisone in hair are valid biomarkers of
      cumulative exposure of cortisol and cortisone to retrospectively reflect long
      term basal activity of the HPA system.

PMID- 29180002
TI  - Melatonin mitigates thioacetamide-induced hepatic fibrosis via antioxidant
      activity and modulation of proinflammatory cytokines and fibrogenic genes.
AB  - AIMS: The potential antifibrotic effects of melatonin against induced hepatic
      fibrosis were explored. MAIN METHODS: Rats were allocated into four groups:
      placebo; thioacetamide (TAA) (200mg/kg bwt, i.p twice weekly for two months);
      melatonin (5mg/kgbwt, i.p daily for a week before TAA and continued for an
      additional two months); and melatonin plus TAA. Hepatic fibrotic changes were
      evaluated biochemically and histopathologically. Hepatic oxidative/antioxidative
      indices were assessed. The expression of hepatic proinflammatory cytokines (tumor
      necrosis factor-alpha, and interleukin-1beta), fibrogenic-related genes
      (transforming growth factor-1beta, collagen I, collagen, III, laminin, and
      autotaxin) and an antioxidant-related gene (thioredoxin-1) were detected by qRT
      PCR. KEY FINDINGS: In fibrotic rats, melatonin lowered serum aspartate
      aminotransferase, alanine aminotransferase, and autotaxin activities, bilirubin,
      hepatic hydroxyproline and plasma ammonia levels. Melatonin displayed
      hepatoprotective and antifibrotic potential as indicated by mild hydropic
      degeneration of some hepatocytes and mild fibroplasia. In addition, TAA induced
      the depletion of glutathione, glutathione s-transferase, glutathione peroxidase,
      superoxide dismutase, catalase, and paraoxonase-1 (PON-1), while inducing the
      accumulation of malondialdehyde, protein carbonyl (C=O) and nitric oxide (NO),
      and DNA fragmentation. These effects were restored by melatonin pretreatment.
      Furthermore, melatonin markedly attenuated the expression of proinflammatory
      cytokines and fibrogenic genes via the upregulation of thioredoxin-1 mRNA
      transcripts. SIGNIFICANCE: Melatonin exhibits potent anti-inflammatory,
      antioxidant and fibrosuppressive activities against TAA-induced hepatic
      fibrogenesis via the suppression of oxidative stress, DNA damage, proinflammatory
      cytokines and fibrogenic gene transcripts. In addition, we demonstrate that the
      antifibrotic activity of melatonin is mediated by the induction of thioredoxin-1
      with attenuation of autotaxin expressions.

PMID- 29180004
TI  - Estimating a person's age from walking over a sensor floor.
AB  - Ageing has an effect on many parameters of the physical condition, and one of
      them is the way a person walks. This property, the gait pattern, can
      unintrusively be observed by letting people walk over a sensor floor. The
      electric capacitance sensors built into the floor deliver information about when
      and where feet get into close proximity and contact with the floor during the
      phases of human locomotion. We processed gait patterns recorded this way by
      extracting a feature vector containing the discretised distribution of occurring
      geometrical extents of significant sensor readings. This kind of feature vector
      is an implicit measure encoding the ratio of swing-to stance phase timings in the
      gait cycle and representing how cleanly the leg swing is performed. We then used
      the dataset to train a Multi-Layer Perceptron to perform regression with the age
      of the person as the target value, and the feature vector as input. With this
      method and a dataset size of 142 persons recorded, we achieved a mean absolute
      error of approximately 10 years between the true age and the estimated age of the
      person. Considering the novelty of our approach, this is an acceptable result.
      The combination of a floor sensor and machine learning methods for interpreting
      the sensor data seems promising for further research and applications in care and
      medicine.

PMID- 29180006
TI  - Modulation of electric brain responses evoked by pitch deviants through
      transcranial direct current stimulation.
AB  - Congenital amusia is a neurodevelopmental disorder, characterized by a difficulty
      detecting pitch deviation that is related to abnormal electrical brain responses.
      Abnormalities found along the right fronto-temporal pathway between the inferior
      frontal gyrus (IFG) and the auditory cortex (AC) are the likely neural mechanism
      responsible for amusia. To investigate the causal role of these regions during
      the detection of pitch deviants, we applied cathodal (inhibitory) transcranial
      direct current stimulation (tDCS) over right frontal and right temporal regions
      during separate testing sessions. We recorded participants' electrical brain
      activity (EEG) before and after tDCS stimulation while they performed a pitch
      change detection task. Relative to a sham condition, there was a decrease in P3
      amplitude after cathodal stimulation over both frontal and temporal regions
      compared to pre-stimulation baseline. This decrease was associated with small
      pitch deviations (6.25 cents), but not large pitch deviations (200 cents).
      Overall, this demonstrates that using tDCS to disrupt regions around the IFG and
      AC can induce temporary changes in evoked brain activity when processing pitch
      deviants. These electrophysiological changes are similar to those observed in
      amusia and provide causal support for the connection between P3 and fronto
      temporal brain regions.

PMID- 29180005
TI  - Leisure-time physical activity across adulthood and biomarkers of cardiovascular
      disease at age 60-64: A prospective cohort study.
AB  - BACKGROUND AND AIMS: This study examined associations between leisure-time
      physical activity (LTPA) across adulthood (from age 36) and cardiovascular
      disease (CVD) biomarkers at age 60-64. METHODS: LTPA was reported by study
      participants from the MRC National Survey of Health and Development at ages 36,
      43, 53 and 60-64 (n = 1754) and categorised as inactive, moderately active (1
      4/month) or most active (5+/month) at each age. Linear regression was used to
      examine associations between a cumulative adulthood LTPA score (range = 0-8), and
      change in LTPA between ages 36 and 60-64 (i.e. always inactive, became inactive,
      became active, always active) and inflammatory [C-reactive protein (CRP),
      interleukin-6 (IL-6)], endothelial [tissue-Plasminogen Activator (t-PA), E
      selectin] and adipokine [leptin, adiponectin] measures extracted from overnight
      fasting blood samples at age 60-64. RESULTS: The more active a participant was
      over adulthood, the better their biomarker profile, e.g. fully-adjusted
      difference in t-PA (both sexes) and adiponectin (women) per unit increase in the
      LTPA score (95% confidence interval) = -2.2% (-3.6; -0.8) and 2.0% (0.2; 3.8).
      Those that became active at age 60-64 showed slightly healthier biomarker
      profiles than those that became inactive [e.g. fully-adjusted difference in IL-6
      = -9.9% (-23.9; 4.1) vs. -3.8% (-12.4; 4.8)], although the best profiles were
      seen for those always active [IL-6: -15.0% (-24.2; -5.7)], when compared with the
      always inactive group. CONCLUSIONS: Greater accumulation of LTPA across adulthood
      was associated with a more favourable CVD biomarker profile in early old age.
      Earlier uptake and long-term maintenance of LTPA may provide the greatest
      benefits for CVD prevention.

PMID- 29180007
TI  - Tyrosine kinase Fyn regulates iNOS expression in LPS-stimulated astrocytes via
      modulation of ERK phosphorylation.
AB  - The high concentrations of nitric oxide (NO) produced by inducible nitric oxide
      synthase (iNOS) in activated glial cells in response to neuroinflammatory stimuli
      have neurotoxic effects on the brain. At basal levels, iNOS expression is low,
      and proinflammatory stimuli induce iNOS expression in astrocytes, microglia, and
      oligodendrocytes. Fyn, a non-receptor tyrosine kinase, regulates iNOS expression
      in several types of immune cells. However, its role in stimulated astrocytes is
      less clear. In this study, we investigated the role of Fyn in the regulation of
      lipopolysaccharide (LPS)-induced iNOS expression in astrocytes from mice and
      rats. Intracerebroventricular LPS injections in cortical regions enhanced iNOS
      mRNA and protein levels, which were increased in Fyn-deficient mice. Accordingly,
      LPS-induced nitrite production was enhanced in primary astrocytes cultured from
      Fyn-deficient mice or rats. Similar results were observed in cultured astrocytes
      after the siRNA-induced knockdown of Fyn expression. Finally, we observed
      increased LPS-induced extracellular signal-regulated protein kinase (ERK)
      activation in Fyn-deficient astrocytes. These results suggested that Fyn has a
      regulatory role in iNOS expression in astrocytes during neuroinflammatory
      responses.

PMID- 29180008
TI  - Identification and characterization of human bone-derived cells.
AB  - This study was designed to identify and characterize primary bone-derived cells
      (BdCs) and investigate the potential role of osteoblast differentiation. Primary
      BdCs were isolated from surgical bone for comparative analysis with mesenchymal
      stem cells (MSCs) and fetal osteoblasts (FOBs) and for potential differentiation
      to mature osteoblasts. Using three different cells, we successfully cultivated
      human osteoblast differentiation and activity which were evaluated using
      microarray and biochemical methods. BdCs are more correlated to MSCs in
      bioinformatics result and similar with FOBs in gene expression. In particular,
      Osterix, osteoprogenitor marker, was high expressed in BdCs, while the expression
      in MSCs and FOBs were very low. Furthermore, BdCs exhibited a marked alkaline
      phosphatase (ALP) expression, early stage of osteogenic marker, and retained
      osteogenic properties and physiological changes into maturation as in FOBs. BdCs
      also showed an increase in bone morphogenic protein 2 (BMP2), osteopontin (OPN),
      and osteocalcin (OCN) mRNA expressions during differentiation. This study
      suggests that BdCs may be osteoprogenitor cells or undifferentiated
      preosteoblasts with strong capacity to differentiate toward mature osteoblasts.

PMID- 29180009
TI  - Regulation of the Plasma Membrane Calcium ATPases by the actin cytoskeleton.
AB  - Associations between the cortical cytoskeleton and the components of the plasma
      membrane are no longer considered to be merely of structural and mechanical
      nature but are nowadays recognized as dynamic interactions that modulate a
      plethora of cellular responses. Reorganization of actin filaments upon diverse
      stimuli - among which is the rise in cytosolic Ca2+ - is involved in cell
      motility and adhesion, phagocytosis, cytokinesis, and secretion. Actin dynamics
      also participates in the regulation of ion transport across the membranes where
      it not only plays a key role in the delivery and stabilization of channels and
      transporters in the plasma membrane but also in the regulation of their activity.
      The recently described functional interaction between actin and the Plasma
      Membrane Ca2+-ATPase (PMCA) represents a novel regulatory mechanism of the pump
      at the time that unveils a new pathway by which the cortical actin cytoskeleton
      participates in the regulation of cytosolic Ca2+ homeostasis. In this review, we
      summarize the current knowledge on the interaction between the cortical actin
      cytoskeleton and the PMCA and discuss the possible mechanisms that may explain
      the pump's modulation.

PMID- 29180010
TI  - Role of N-myristoylation in stability and subcellular localization of the CLPABP
      protein.
AB  - Cardiolipin and phosphatidic acid-binding protein (CLPABP) controls the stability
      of the mRNA harboring an AU-rich element (ARE) in the 3' UTR with the help of the
      RNA stabilizer, human antigen R (HuR). Although CLPABP is localized on the
      mitochondrial surface as a large protein-RNA complex, its precise role is not yet
      known. Recently, CLPABP was identified as an N-myristoylated protein. Here, we
      demonstrate the effects of N-myristoylation on the functions of CLPABP. In the
      present study, compared to the wild-type protein that possessed the "MG" motif at
      the N-terminus for N-myristoylation, the mutant CLPABP protein that lacked N
      myristoylation modification site was unstable. Furthermore, the expression of the
      G/A mutant of CLPABP, which lacked N-myristoylation site, induced morphological
      alterations in mitochondria. Because pleckstrin homology domain-deleted mutant,
      which was fused with the N-myristoylation site derived from intact CLPABP, could
      not colocalize with mitochondria, N-myristoylation of CLPABP was predicted to
      affect its stability onto the mitochondrial membrane rather than its subcellular
      localization.

PMID- 29180011
TI  - Unbiased compound screening with a reporter gene assay highlights the role of p13
      in the cardiac cellular stress response.
AB  - We recently showed that a 13-kDa protein (p13), the homolog protein of formation
      of mitochondrial complex V assembly factor 1 in yeast, acts as a potential
      protective factor in pancreatic islets under diabetes. Here, we aimed to identify
      known compounds regulating p13 mRNA expression to obtain therapeutic insight into
      the cellular stress response. A luciferase reporter system was developed using
      the putative promoter region of the human p13 gene. Overexpression of peroxisome
      proliferator-activated receptor gamma coactivator 1alpha, a master player
      regulating mitochondrial metabolism, increased both reporter activity and p13
      expression. Following unbiased screening with 2320 known compounds in HeLa cells,
      12 pharmacological agents (including 8 cardiotonics and 2 anthracyclines) that
      elicited >2-fold changes in p13 mRNA expression were identified. Among them, four
      cardiac glycosides decreased p13 expression and concomitantly elevated cellular
      oxidative stress. Additional database analyses showed highest p13 expression in
      heart, with typically decreased expression in cardiac disease. Accordingly, our
      results illustrate the usefulness of unbiased compound screening as a method for
      identifying novel functional roles of unfamiliar genes. Our findings also
      highlight the importance of p13 in the cellular stress response in heart.

PMID- 29180012
TI  - Weighted gene co-expression network analysis reveals potential genes involved in
      early metamorphosis process in sea cucumber Apostichopus japonicus.
AB  - Sea cucumbers, one main class of Echinoderms, have a very fast and drastic
      metamorphosis process during their development. However, the molecular basis
      under this process remains largely unknown. Here we systematically examined the
      gene expression profiles of Japanese common sea cucumber (Apostichopus japonicus)
      for the first time by RNA sequencing across 16 developmental time points from
      fertilized egg to juvenile stage. Based on the weighted gene co-expression
      network analysis (WGCNA), we identified 21 modules. Among them, MEdarkmagenta was
      highly expressed and correlated with the early metamorphosis process from late
      auricularia to doliolaria larva. Furthermore, gene enrichment and differentially
      expressed gene analysis identified several genes in the module that may play key
      roles in the metamorphosis process. Our results not only provide a molecular
      basis for experimentally studying the development and morphological complexity of
      sea cucumber, but also lay a foundation for improving its emergence rate.

PMID- 29180013
TI  - Development of a novel cellulase biosensor that detects crystalline cellulose
      hydrolysis using a transcriptional regulator.
AB  - Successful utilization of cellulose as renewable biomass depends on the
      development of economically feasible technologies, which can aid in enzymatic
      hydrolysis. In this study, we developed a whole-cell biosensor for detecting
      cellulolytic activity that relies on the recognition of cellobiose using the
      transcriptional factor CelR from Thermobifida fusca and transcriptional
      activation of its downstream gfp reporter gene. The fluorescence intensity of
      whole-cell biosensor, which was named as cellobiose-detectible genetic enzyme
      screening system (CBGESS), was directly proportional to the concentration of
      cellobiose. The strong fluorescence intensity of CBGESS demonstrated the ability
      to detect cellulolytic activity with two cellulosic substrates, carboxymethyl
      cellulose and p-nitrophenyl beta-D-cellobioside in cellulase-expressing
      Escherichia coli. In addition, CBGESS easily sensed crystalline cellulolytic
      activity when commercial Celluclast 1.5L was dropped on an Avicel plate.
      Therefore, CBGESS is a powerful tool for detecting cellulolytic activity with
      high sensitivity in the presence of soluble or insoluble cellulosic substrates.
      CBGESS may be further applied to excavate novel cellulases or microbes from both
      genetic libraries and various environments.

PMID- 29180014
TI  - Structural insights into the oligomerization of FtsH periplasmic domain from
      Thermotoga maritima.
AB  - Prompt removal of misfolded membrane proteins and misassembled membrane protein
      complexes is essential for membrane homeostasis. However, the elimination of
      these toxic proteins from the hydrophobic membrane environment has high energetic
      barriers. The transmembrane protein, FtsH, is the only known ATP-dependent
      protease responsible for this task. The mechanisms by which FtsH recognizes,
      unfolds, translocates, and proteolyzes its substrates remain unclear. The
      structure and function of the ATPase and protease domains of FtsH have been
      previously characterized while the role of the FtsH periplasmic domain has not
      clearly identified. Here, we report the 1.5-1.95 A resolution crystal structures
      of the Thermotoga maritima FtsH periplasmic domain (tmPD) and describe the
      dynamic features of tmPD oligomerization.

PMID- 29180015
TI  - Pyruvic acid prevents Cu2+/Zn2+-induced neurotoxicity by suppressing
      mitochondrial injury.
AB  - Zinc (Zn) is known as a co-factor for over 300 metalloproteins or enzymes, and
      has essential roles in many physiological functions. However, excessively high Zn
      concentrations are induced in pathological conditions such as interruption of
      blood flow in stroke or transient global ischemia-induced neuronal cell death.
      Furthermore, we recently found that copper (Cu2+) significantly exacerbates Zn2+
      neurotoxicity in mouse hypothalamic neuronal cells, suggesting that Zn2+
      interaction with Cu2+ is important for the development of neurological disease.
      Meanwhile, organic acids such as pyruvic acid and citric acid are reported to
      prevent neuronal cell death induced by various stresses. Thus, in this study, we
      focused on organic acids and searched for compounds that inhibit Cu2+/Zn2+
      induced neurotoxicity. Initially, we examined the protective effect of various
      organic acids on Cu2+/Zn2+-induced neurotoxicity, and found that pyruvic acid
      clearly suppresses Cu2+/Zn2+-induced neurotoxicity in GT1-7 cells. Next, we
      examined the protective mechanisms of pyruvic acid against Cu2+/Zn2+-induced
      neurotoxicity. Specifically, we examined the possibilities that pyruvic acid
      chelates Cu2+ and Zn2+ or suppresses the ER stress response, but found that
      neither was suppressed by pyruvic acid treatment. In contrast, pyruvic acid
      significantly suppressed cytochrome c release into cytoplasm, an index of
      mitochondrial injury, in a dose-dependent manner. These results suggest that
      pyruvic acid prevents Cu2+/Zn2+-induced neuronal cell death by suppressing
      mitochondrial injury. Based on our results, we assume that pyruvic acid may be
      therapeutically beneficial for neurological diseases involving neuronal cell
      death such as vascular dementia.

PMID- 29180016
TI  - Cytochrome P450 CYP716A254 catalyzes the formation of oleanolic acid from beta
      amyrin during oleanane-type triterpenoid saponins biosynthesis in Anemone
      flaccida.
AB  - Anemone flaccida Fr. Shmidt (Ranunculaceae), known as 'Di Wu' in China, is a
      perennial herb which has long been used to treat arthritis. The rhizome of A.
      flaccida contains pharmacologically active components i.e. oleanane-type
      triterpenoid saponins. Oleanolic acid is natural triterpenoid in plants with
      diverse biological activities. The biosynthesis of oleanolic acid involves
      cyclization of 2,3-oxidosqualene to the oleanane-type triterpenoid skeleton,
      followed by a series of oxidation reactions catalyzed by cytochrome P450
      monooxygenase (CYP450). Previously, we identified four possible cytochrome P450
      genes belonging to CYP716A subfamily from the transcriptome of A. flaccida. In
      this study, we identified one of those genes "CYP716A254" encoding a cytochrome
      P450 monooxygenase from A. flaccida that catalyzes the conversion of the beta
      amyrin into oleanolic acid. The heterologous expression of CYP716A254 in yeast
      resulted in oxidation of beta-amyrin at the C-18 position to oleanolic acid
      production. These results provide an important basis for further studies of
      oleanane-type triterpenoid saponins synthesis in A. flaccida.

PMID- 29180017
TI  - Role of osteopontin and its regulation in pancreatic islet.
AB  - Osteopontin (OPN) is involved in various physiological processes and also
      implicated in multiple pathological states. It has been suggested that OPN may
      have a role in type 2 diabetes (T2D) by protecting pancreatic islets and
      interaction with incretins. However, the regulation and function of OPN in
      islets, especially in humans, remains largely unexplored. In this study, we
      performed our investigations on both diabetic mouse model SUR1-E1506K+/+ and
      islets from human donors. We demonstrated that OPN protein, secretion and gene
      expression was elevated in the diabetic SUR1-E1506K+/+ islets. We also showed
      that high glucose and incretins simultaneously stimulated islet OPN secretion. In
      islets from human cadaver donors, OPN gene expression was elevated in diabetic
      islets, and externally added OPN significantly increased glucose-stimulated
      insulin secretion (GSIS) from diabetic but not normal glycemic donors. The
      increase in GSIS by OPN in diabetic human islets was Ca2+ dependent, which was
      abolished by Ca2+-channel inhibitor isradipine. Furthermore, we also confirmed
      that OPN promoted cell metabolic activity when challenged by high glucose. These
      observations provided evidence on the protective role of OPN in pancreatic islets
      under diabetic condition, and may point to novel therapeutic targets for islet
      protection in T2D.

PMID- 29180018
TI  - Isoliquiritigenin protects against sepsis-induced lung and liver injury by
      reducing inflammatory responses.
AB  - Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ
      failure, mainly due to uncontrolled inflammatory responses. Despite accumulating
      knowledge obtained in recent years, effective drugs to treat sepsis in the clinic
      are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been
      reported to exert anti-inflammatory properties. However, little is known about
      the effects of ISL on sepsis and its related complications. In this study, we
      investigated the potential protective effects of ISL on lipopolysaccharide (LPS)
      induced injuries and identified the mechanisms underlying these effects. ISL
      inhibited inflammatory cytokine expression in mouse primary peritoneal
      macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL
      prevented LPS-induced structural damage and inflammatory cell infiltration.
      Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver
      injury, accompanied by a reduction in inflammatory responses. Moreover, these
      protective effects were mediated by the nuclear factor kappa B (NF-kappaB)
      pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our
      study suggests that ISL may be a potential therapeutic agent for sepsis-induced
      injuries.

PMID- 29180019
TI  - Overcoming challenges for amplified expression of recombinant proteins using
      Escherichia coli.
AB  - A thorough characterisation of the genetics, physiology and metabolism of
      Escherichia coli has led to the availability of a large number of strains and
      vectors suitable for recombinant protein expression. Despite the relative ease in
      using E. coli for achieving amplified expression of many recombinant proteins,
      for some proteins this can be a frustrating and time-consuming process leading to
      very low expression or no expression at all. This is especially true for membrane
      proteins, which introduce additional challenges. A number of factors can be
      considered and optimised for achieving required levels of amplified expression of
      recombinant proteins in E. coli that are broadly classified as host strain,
      expression vector and growth conditions. In this paper we summarise these factors
      and consolidate the common challenges encountered and approaches to overcome
      them, focusing in particular on cases where there is low amplified expression or
      no expression at all of the desired recombinant protein, due to various reasons.

PMID- 29180020
TI  - Aptamers in Bordeaux 2017: An exceptional "millesime".
AB  - About 150 participants attended the symposium organised at the Palais de la
      Bourse in Bordeaux, France on September 22-23, 2017. Thirty speakers from all
      over the world delivered lectures covering selection processes, aptamer chemistry
      and innovative applications of these powerful tools that display major advantages
      over antibodies. Beyond the remarkable science presented, lively discussion and
      fruitful exchange between participants made this meeting a great success. A
      series of lectures were focused on synthetic biology (riboswitches, new synthetic
      base pairs, mutated polymerases). Innovative selection procedures including
      functional screening of oligonucleotide pools were described. Examples of
      aptasensors for the detection of pathogens were reported. The potential of
      aptamers for the diagnostic and the treatment of diseases was also presented.
      Brief summaries of the lectures presented during the symposium are given in this
      report. The third edition of this symposium will take place in Boulder, Colorado
      in Summer 2018 (information available at http://www.aptamers-in-bordeaux.com/).

PMID- 29180021
TI  - Insulin resistance in 3T3-L1 adipocytes by TNF-alpha is improved by punicic acid
      through upregulation of insulin signalling pathway and endocrine function, and
      downregulation of proinflammatory cytokines.
AB  - Insulin resistance (IR) has become a major threat to public health due to its
      role in metabolic syndrome. Inflammation associated with IR is an interesting
      area of biomedical research in recent years and is expected to affect insulin
      signalling pathway via downregulating glucose transporters. In the present study,
      we evaluate the potential of punicic acid (PA), a nutraceutical found in
      pomegranate seed oil, against TNF-alpha induced alteration in 3T3-L1 adipocytes
      on glucose metabolism, endocrine function and inflammation. IR was induced in 3T3
      L1 adipocytes by treating with TNF-alpha (10 ng/mL) and various concentrations of
      PA (5, 10, 30 MUM) were incubated simultaneously. After 24 h, we found that TNF
      alpha treatment increased mRNA expression of SOCS3, PTP1B and a decrease in IRS1
      causing diminished glucose uptake. Further, it showed significantly increased
      transcriptional activity of NFkappaB and leptin secretion while PA maintained
      leptin levels normal. Additionally, PA prevented the over-expression of
      phosphorylated JNK in a dose dependent manner during IR. PA also ameliorated
      significantly the upregulation of proinflammatory cytokines. From the results, we
      conclude that PA is effective to ameliorate TNF-alpha induced IR and also we
      recommend the intake of PA for control and management of IR and its associated
      complications.

PMID- 29180022
TI  - Toxicological assessment of lower alkyl methacrylate esters by a category
      approach.
AB  - Categories and read-across are essential tools for supplying information for
      assessments of endpoints without data while minimizing animal testing. This study
      is based on the guidance of ECHA in its Read-Across Framework (RAAF). A category
      of C1 - C8 alkyl methacrylate esters (methyl, ethyl, n-butyl, iso-butyl and 2
      ethylhexyl) was constructed to fill in missing information for human health
      endpoints using read-across as a permitted adaptation under EU REACH. The esters
      form a series with common functional groups, small incremental changes of
      electrophilicity by molecular weight, and rapid hydrolysis by ester cleavage.
      Read-across is justified by two common specific modes of action, direct
      electrophilic reaction of the parent compounds and the potential inherent
      toxicities of the common metabolites methacrylic acid and the corresponding
      alcohols. The toxicological profile is very similar for all category members and
      not driven by the alcohol metabolites. Data gaps can be filled in with high
      confidence based on the number of studies available, the effects therein observed
      and the toxicological profiles of the hydrolysis products. The guidance provided
      by the RAAF enabled data gaps to be filled in a robust manner.

PMID- 29180023
TI  - Effect of Patiromer on Hyperkalemia Recurrence in Older Chronic Kidney Disease
      Patients Taking RAAS Inhibitors.
AB  - BACKGROUND: Older people are predisposed to hyperkalemia because of impaired
      renal function, comorbid conditions, and polypharmacy. Renin-angiotensin
      aldosterone system inhibitors (RAASi), which are recommended to treat chronic
      kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed
      potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum
      potassium in patients with chronic kidney disease taking RAASi. We studied the
      efficacy and safety of patiromer in a prespecified subgroup of patients aged >=65
      years from OPAL-HK. METHODS: Chronic kidney disease patients with mild or
      moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8
      g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients
      entered an 8-week randomized withdrawal phase (part B) and continued patiromer or
      switched to placebo. RESULTS: Mean +/- standard error change in serum potassium
      from baseline to week 4 of part A (primary endpoint) in patients aged >=65 years
      was -1.01 +/- 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L.
      The serum potassium increase during the first 4 weeks of part B was greater in
      patients taking placebo than in those taking patiromer (P < .001). Fewer patients
      taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum
      potassium >=5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A)
      and 7% (part B) of patients aged >=65 years. Serum potassium <3.5 mEq/L and serum
      magnesium <1.4 mg/dL were infrequent (4% each in patients aged >=65 years in part
      A). CONCLUSIONS: Patiromer reduced recurrent hyperkalemia and was well tolerated
      in older chronic kidney disease patients taking RAASi.

PMID- 29180024
TI  - Impact of Home Health Care on Health Care Resource Utilization Following Hospital
      Discharge: A Cohort Study.
AB  - BACKGROUND: As healthcare costs rise, home health care represents an opportunity
      to reduce preventable adverse events and costs following hospital discharge. No
      studies have investigated the utility of home health care within the context of a
      large and diverse patient population. METHODS: A retrospective cohort study was
      conducted between 1/1/2013 and 6/30/2015 at a single tertiary care institution to
      assess healthcare utilization after discharge with home health care. Control
      patients discharged with "self-care" were matched by propensity score to home
      health care patients. The primary outcome was total healthcare costs in the 365
      day post-discharge period. Secondary outcomes included follow-up readmission and
      death. Multivariable linear and Cox proportional hazards regression were used to
      adjust for covariates. RESULTS: Among 64,541 total patients, 11,266 controls were
      matched to 6,363 home health care patients across 11 disease-based Institutes.
      During the 365-day post-discharge period, home health care was associated with a
      mean unadjusted savings of $15,233 per patient, or $6,433 after adjusting for
      covariates (p < 0.0001). Home health care independently decreased the hazard of
      follow-up readmission (HR 0.82, p < 0.0001) and death (HR 0.80, p < 0.0001).
      Subgroup analyses revealed that home health care most benefited patients
      discharged from the Digestive Disease (death HR 0.72, p < 0.01), Heart & Vascular
      (adjusted savings of $11,453, p < 0.0001), Medicine (readmission HR 0.71, p <
      0.0001), and Neurological (readmission HR 0.67, p < 0.0001) Institutes.
      CONCLUSIONS: Discharge with home health care was associated with significant
      reduction in healthcare utilization and decreased hazard of readmission and
      death. These data inform development of value-based care plans.

PMID- 29180025
TI  - Delay from Diagnosis to Surgery in Transferred Type A Aortic Dissection.
AB  - OBJECTIVES: The purpose of this research is to analyze factors associated with
      delays to surgical management of Type A acute aortic dissection patients.
      METHODS: Time from diagnosis to surgery and associated factors were evaluated in
      1880 surgically managed Type A dissection patients enrolled in the International
      Registry of Acute Aortic Dissection. RESULTS: The majority of patients were
      transferred (75.7% vs 24.3%). Patients who were transferred had a median delay
      from diagnosis to surgery of 4.0 hours (interquartile range 2.5-7.2 hours),
      compared with 2.3 hours (interquartile range 1.1-4.2 hours; P < .001) in
      nontransferred patients. Among patients who were transferred, those with worst
      ever, posterior, or tearing chest pain those with severe complications, and those
      receiving transthoracic echocardiogram prior to a transesophageal echocardiogram
      or as the only echocardiogram were treated more quickly. Those undergoing
      magnetic resonance imaging, or who had prior cardiac surgery, had longer delays
      to surgery. Among nontransferred patients, those with coma were treated more
      quickly. In both groups, patients presenting with emergent conditions such as
      cardiac tamponade, hypotension, or shock had more rapid treatment. Among
      transferred patients, surviving patients had longer delays (4.1 [2.6-7.8] hours
      vs 3.3 [2.0-6.0] hours, P = .001). Overall mortality did not differ between
      patients who were transferred vs not (19.3% vs 21.1%, P = .416). CONCLUSION:
      Simply being transferred added significantly to the delay to surgery for Type A
      acute aortic dissection patients, but a number of factors affected its extent.
      Overall, signs and symptoms leading to a definitive diagnosis or indicating
      immediate life threat reduced time to surgery, while factors suggesting other
      diagnoses correlated with delays.

PMID- 29180026
TI  - Intramolecular and Intermolecular FRET Sensors for GPCRs - Monitoring
      Conformational Changes and Beyond.
AB  - Within the past decade, a large increase in structural knowledge from
      crystallographic studies has significantly fostered our understanding of the
      structural biology of G protein-coupled receptors (GPCRs). However, information
      on dynamic events upon receptor activation or deactivation is not yet readily
      accessed by these structural approaches. GPCR-based fluorescence resonance energy
      transfer or bioluminescence resonance energy transfer sensors or sensors for
      interacting proteins (e.g., G proteins or arrestins) can in part cover this gap.
      The principal design of such sensors was reported 15 years ago. Since then,
      sensors for almost 20 different GPCRs have been designed. If used with necessary
      controls and cautious interpretation, such sensors can contribute significantly
      to our understanding of the basic mechanisms of GPCR function and beyond. In this
      review, we will discuss the recent developments in this area of GPCR dynamics.

PMID- 29180027
TI  - Nasopharyngeal s. pneumoniae carriage and density in Belgian infants after 9
      years of pneumococcal conjugate vaccine programme.
AB  - BACKGROUND: In Belgium, the infant pneumococcal conjugate vaccine (PCV) programme
      changed from PCV7 (2007-2011) to PCV13 (2011-2015) and to PCV10 (2015-2016). A 3
      year nasopharyngeal carriage study was initiated during the programme switch in
      2016. Main objective of the year 1 assessment was to obtain a baseline
      measurement of pneumococcal carriage prevalence, carriage density, serotype
      distribution and antibiotic resistance. MATERIALS/METHODS: Two infant populations
      aged 6-30 months and without use of antibiotics in the seven days prior to
      sampling were approached: (1) attending one of 85 randomly selected day-care
      centres (DCC); (2) presenting with AOM at study-trained general practitioners and
      paediatricians. Demographic and clinical characteristics were documented and a
      single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for
      antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT
      PCR) targeting LytA was performed. RESULTS: Culture-based (DCC: 462/760; 60.8% -
      AOM: 27/39; 69.2%) and LytA-based (DCC: 603/753; 80.1% - AOM: 32/39; 82.1%)
      carriage prevalence was high. Average pneumococcal DNA load in LytA-positive day
      care samples was 6.5 * 106 copies/ul (95%CI = 3.9-9.2 * 106, median = 3.5 * 105);
      DNA load was positively associated with signs of common cold and negatively with
      previous antibiotic use. Culture-based frequency of 13 pneumococcal vaccine (PCV)
      serotypes was 5.4% in DCC and 7.7% in AOM, with 19F and 14 being most frequent,
      and frequencies below 0.5% for serotypes 3, 6A, 19A in both populations.
      Predominant non-PCV serotypes were 23B and 23A in day-care and 11A in infants
      with AOM. In day-care, resistance to penicillin was rare (<0.5%) and absent
      against levofloxacin; 32.7% and 16.9% isolates were cotrimoxazole- and
      erythromycin-resistant respectively. CONCLUSION: Four years after PCV13
      introduction in the vaccination programme, PCV13 serotype carriage was rare in
      infants throughout Belgium and penicillin resistance was rare. Continued
      surveillance in the context of a PCV programme switch is necessary.

PMID- 29180029
TI  - Vaccine hesitancy terminology: A response to Bedford et al.

PMID- 29180028
TI  - Dual-route targeted vaccine protects efficiently against botulinum neurotoxin A
      complex.
AB  - Clostridium botulinum readily persists in the soil and secretes life-threatening
      botulinum neurotoxins (BoNTs) that are categorized into serotypes A to H, of
      which, serotype A (BoNT/A) is the most commonly occurring in nature. An
      efficacious vaccine with high longevity against BoNT intoxication is urgent.
      Herein, we developed a dual-route vaccine administered over four consecutive
      weeks by mucosal and parenteral routes, consisting of the heavy chain (Hc) of
      BoNT/A targeting dendritic cell peptide (DCpep) expressed by Lactobacillus
      acidophilus as a secretory immunogenic protein. The administered dual-route
      vaccine elicited robust and long-lasting memory B cell responses comprising
      germinal center (GC) B cells and follicular T cells (Tfh) that fully protected
      mice from lethal oral BoNT/A fatal intoxication. Additionally, passively
      transferring neutralizing antibodies against BoNT/A into naive mice induced
      robust protection against BoNT/A lethal intoxication. Together, a targeted
      vaccine employing local and systemic administrative routes may represent a novel
      formulation eliciting protective B cell responses with remarkable longevity
      against threatening biologic agents such as BoNTs.

PMID- 29180030
TI  - The efficacy of recombinant turkey herpesvirus vaccines targeting the H5 of
      highly pathogenic avian influenza virus from the 2014-2015 North American
      outbreak.
AB  - The outbreak of highly pathogenic avian influenza virus in North American poultry
      during 2014 and 2015 demonstrated the devastating effects of the disease and
      highlighted the need for effective emergency vaccine prevention and control
      strategies targeted at currently circulating strains. This study evaluated the
      efficacy of experimental recombinant turkey herpesvirus vector vaccines with
      three different inserts targeting the hemagglutinin gene of an isolate from the
      recent North American influenza outbreak. White leghorn chickens were vaccinated
      at one day of age and challenged with A/Turkey/Minnesota/12582/2015 H5N2 at 4
      weeks of age. Birds were analyzed for survival, viral shedding at two and four
      days after infection, and specific antibody prior to challenge and from surviving
      birds. The three experimental vaccines demonstrated 100%, 45% and 15% survival
      with the most effective vaccine significantly reducing oral and cloacal viral
      shedding compared to all other groups and generated specific antibody prior to
      challenge with highly pathogenic avian influenza virus. More studies are needed
      using diverse H5Nx highly pathogenic virus isolates to fully determine the
      breadth of coverage against possible exposure strains, as well as possible impact
      of maternally derived antibody on protection and vaccine efficacy.

PMID- 29180031
TI  - Will we have new pertussis vaccines?
AB  - Despite wide vaccination coverage with efficacious vaccines, pertussis is still
      not under control in any country. Two types of vaccines are available for the
      primary vaccination series, diphtheria/tetanus/whole-cell pertussis and
      diphtheria/tetanus/acellular pertussis vaccines, in addition to reduced antigen
      content vaccines recommended for booster vaccination. Using these vaccines,
      several strategies are being explored to counter the current pertussis problems,
      including repeated vaccination, cocoon vaccination and maternal immunization.
      With the exception of the latter, none have proven their effectiveness, and even
      maternal vaccination is not expected to ultimately control pertussis. Therefore,
      new pertussis vaccines are needed, and several candidates are in early pre
      clinical development. They include whole-cell vaccines with low endotoxin
      content, outer membrane vesicles, new formulations, acellular vaccines with new
      adjuvants or additional antigens and live attenuated vaccines. The most advanced
      is the live attenuated nasal vaccine BPZE1. It provides strong protection in mice
      and non-human primates, is safe, even in immune compromised animals, and
      genetically stable after in vitro and in vivo passages. It also has interesting
      immunoregulatory properties without being immunosuppressive. It has successfully
      completed a first-in-man clinical trial, where it was found to be safe, able to
      transiently colonize the human respiratory tract and to induce immune responses
      in the colonized subjects. It is now undergoing further clinical development. As
      it is designed to reduce carriage and transmission of Bordetella pertussis, it
      may hopefully contribute to the ultimate control of pertussis.

PMID- 29180032
TI  - Composition and transcription of all interferon regulatory factors (IRFs), IRF1
      11 in a perciform fish, the mandarin fish, Siniperca chuatsi.
AB  - Interferon regulatory factors (IRFs) are a family of mediators in various
      biological processes including immune modulation of interferon (IFN) and
      proinflammatory cytokine expression. However, the data on the complete
      composition of IRFs is rather limited in teleost fish. In the present study, all
      IRF members, i.e. IRF1-11 with two IRF4, IRF4a and IRF4b have been characterised
      in an aquaculture species of fish, the mandarin fish, Siniperca chuatsi, in
      addition to the previous report of IRF1, IRF2, IRF3 and IRF7 from the fish. These
      IRFs are constitutively expressed in various organs/tissues of the fish, and
      their expression can be induced following the stimulation of
      polyinosinic:polycytidylic acid (poly(I:C)) and the infection of infectious
      spleen and kidney necrosis virus (ISKNV), a viral pathogen of mandarin fish in
      aquaculture. The ISKNV infection induced the significant increase in the
      expression of some IRF genes, i.e. IRF2, IRF4a, IRF7, IRF9, IRF10 at 24 or 36 h
      post-infection (hpi) in spleen and head-kidney, and the significant increase of
      some other IRF genes, e.g. IRF1, IRF3, IRF4b, IRF5, IRF6, IRF8 at later stage of
      infection from 72, or 96, or even 120 hpi, which may imply the inhibitory effect
      of ISKNV on fish immune response. It is considered that the present study
      provides the first detailed analysis on all IRF members in an aquaculture species
      of fish, and can be served as the base for further investigation on the role of
      IRFs in teleost fish.

PMID- 29180034
TI  - Surgical Stabilization of Rib Fractures: A Single Institution Experience.
AB  - BACKGROUND: Use of surgical stabilization of rib fractures (SSRF) has increased.
      Despite compelling small studies, many centers still struggle with determining
      criteria for intervention. We investigated the benefit of SSRF in our patients
      compared with nonoperative (NonOp) National Trauma Databank (NTDB) controls,
      specifically in the older population. STUDY DESIGN: We performed a retrospective
      comparison of trauma patients with >=3 and >5 rib fractures, who underwent SSRF
      at a tertiary care level I trauma center, with nonoperatively managed NTDB
      controls from equivalent level I centers between 2007 and 2014. The main outcomes
      measures included mortality, pneumonia, length of stay (LOS), ICU LOS, ventilator
      use, and tracheostomy rates. RESULTS: Overall, SSRF patients were older, had a
      higher percentage of respiratory disease, and higher Injury Severity Scores
      (ISS). Despite more respiratory disease in SSRF patients vs NonOp (p < 0.0001),
      there was no difference in ventilator usage. Results of SSRF included decreases
      in mortality (12%, p = 0.008) and pneumonia (13%, p < 0.001) compared with NonOp
      on propensity score matching. On subgroup analysis of patients 65 years of age or
      older, ISS was higher in the SSRF group. Mortality was significantly lower for
      SSRF vs NonOp, even with higher frequency of respiratory disease within the group
      (p < 0.001). CONCLUSIONS: Patients who underwent SSRF at our institution had
      improved outcomes despite a higher percentage of respiratory disease, compared
      with patients who were managed nonoperatively nationwide. Mortality rates
      improved for patients aged 65 and older, suggesting that this patient population
      may benefit more from SSRF.

PMID- 29180033
TI  - Bioluminescent tracing of a Yersinia pestis pCD1+-mutant and Yersinia
      pseudotuberculosis in subcutaneously infected mice.
AB  - Yersinia pestis has evolved from Yersinia pseudotuberculosis serotype O:1b. A
      typical Y. pestis contains three plasmids: pCD1, pMT1 and pPCP1. However, some
      isolates only harbor pCD1 (pCD1+-mutant). Y. pestis and Y. pseudotuberculosis
      share a common plasmid (pCD1 or pYV), but little is known about whether Y.
      pseudotuberculosis exhibited plague-inducing potential before it was evolved into
      Y. pestis. Here, the luxCDABE::Tn5::kan was integrated into the chromosome of the
      pCD1+-mutant, Y. pseudotuberculosis or Escherichia coli K12 to construct stable
      bioluminescent strains for investigation of their dissemination in mice by
      bioluminescence imaging technology. After subcutaneous infection, the pCD1+
      mutant entered the lymph nodes, followed by the liver and spleen, and,
      subsequently, the lungs, causing pathological changes in these organs. Y.
      pseudotuberculosis entered the lymph nodes, but not the liver, spleen and lungs.
      It also resided in the lymph nodes for several days, but did not cause
      lymphadenitis or pathological lesions. By contrast, E. coli K12-lux was not
      isolatable from mouse lymph nodes, liver, spleen and lungs. These results
      indicate that the pCD1+-mutant can cause typical bubonic and pneumonic plague
      like diseases, and Y. pestis has inherited lymphoid tissue tropism from its
      ancestor rather than acquiring these properties independently.

PMID- 29180036
TI  - Sphingosine 1-phosphate regulates proliferation, cell cycle and apoptosis of
      hepatocellular carcinoma cells via syndecan-1.
AB  - Sphingosine 1-phosphate (S1P) plays an important role in hepatocarcinogenesis. We
      previously demonstrated that S1P induced epithelial-mesenchymal transition of
      hepatocellular carcinoma (HCC) cells via an MMP-7/Syndecan-1/TGF-beta autocrine
      loop. In the present study, we investigated the regulative role of S1P in cell
      survival and progression of HCC cells, and tested whether syndecan-1 is required
      in the S1P action. After transfected with syndecan-1 shRNA, HepG2 and SMMC7721
      cells were treated with S1P for 72 h, and then cell proliferation was detected by
      CCK8 assay, and cell cycle progression and cell apoptosis were detected by flow
      cytometry. The levels of apoptosis markers including cleaved-Caspase-3 and
      cleaved-PARP in SMMC7721 cells were examined by western blotting. Results showed
      that S1P significantly enhanced cell proliferation in HCC cells, which was
      significantly inhibited by syndecan-1 shRNA. S1P induced the cell proportion in S
      phase in HCC cells, whereas S1P decreased the proportion of cells in both early
      and late apoptosis. Syndecan-1 shRNA induced the G2/M arrest in the presence of
      S1P. In the syndecan-1 shRNA transfected HCC cells, the proportions of late and
      early apoptotic cells, and levels of cleaved-Caspase-3 and cleaved-PARP were
      significantly increased in cells with or without S1P treatment. Thus, S1P
      augments the proportion of cells in S phase of the cell cycle that might
      translate to enhance HCC cell proliferation and inhibit the cell apoptosis via
      syndecan-1.

PMID- 29180035
TI  - Prevalence and characteristics of overweight and obesity among Chinese youth aged
      12-18 years: a multistage nationwide survey.
AB  - OBJECTIVE: The aims of the current study were to assess the prevalence of
      overweight and obesity by four different references and to explore the
      characteristics of adolescent overweight and obesity in Chinese secondary school
      students aged 12-18 years. STUDY DESIGN: A cross-sectional study was conducted in
      this study. METHODS: Using stratified random cluster sampling, 8999 secondary
      school students were enrolled. The references developed by Must and Dallal and
      Dietz, the Childhood Obesity Working Group of the International Obesity Task
      Force, the US Centers for Disease Control and Prevention, and the Group of China
      Obesity Task Force (GCOTF reference) were used to identify overweight and obese
      students. RESULTS: The prevalence of adolescent overweight and obesity vary
      substantially based on the four references. The prevalence of adolescent
      overweight and obesity based on GCOTF reference are 8.4% and 4.1%, respectively,
      which is significantly lower than the prevalence of overweight and obesity in
      their peers in 2000 (chi2 = 24.03, P < 0.01). The prevalence of overweight and
      obesity in boys are 12.0% and 5.7%, which are higher than those in girls, 4.6%
      and 5.7% (chi2 = 240.68, P < 0.01). The prevalence of overweight and obesity in
      singletons are higher than those in non-singletons (chi2 = 40.25, P < 0.01). The
      prevalence of overweight and obesity in students with lower school community
      ladder of subjective social status are higher than those from higher ones (chi2 =
      21.61, P < 0.01). CONCLUSION: The GCOTF reference is more suitable for screening
      overweight and obesity in Chinese adolescents. The current prevalence rates of
      adolescent overweight and obesity decreased, and girls made a tremendous
      contribution to this decreasing trend. Singletons and adolescents in lower school
      community ladder of subjective socio-economic status may be at higher risk of
      getting overweight and obesity. More effective strategies with full consideration
      to the characteristics above should be developed to control and prevent
      adolescent overweight and obesity.

PMID- 29180037
TI  - MIR-10b IS inversely correlated with higher tumor grade in osteosarcoma.

PMID- 29180038
TI  - Association of Multiple Phosphorylated Proteins with the 14-3-3 Regulatory Hubs:
      Problems and Perspectives.
AB  - 14-3-3 proteins are well-known universal regulators binding a vast number of
      partners by recognizing their phosphorylated motifs, typically located within the
      intrinsically disordered regions. The abundance of such phosphomotifs ensures the
      involvement of 14-3-3 proteins in sophisticated protein-protein interaction
      networks that govern vital cellular processes. Thousands of 14-3-3 partners have
      been either experimentally identified or predicted, but the spatiotemporal
      hierarchy of the processes based on 14-3-3 interactions is not clearly
      understood. This is exacerbated by the lack of available structural information
      on full regulatory complexes involving 14-3-3, which resist high-resolution
      structural studies due to the presence of intrinsically disordered regions.
      Although deducing three-dimensional structures is of particular urgency,
      structural advances are lagging behind the rate at which novel 14-3-3 partners
      are discovered. Here I attempted to critically review the current state of the
      field and in particular to dissect the unknowns, focusing on questions that could
      help in moving the frontiers forward.

PMID- 29180039
TI  - Regioselective ester cleavage of di-(2-ethylhexyl) trimellitates by porcine liver
      esterase.
AB  - In a comparative study the ester hydrolysis of the plasticizers di-(2-ethylhexyl)
      phthalate (DEHP) and tri-(2-ethylhexyl) trimellitate (TEHTM) as well as of the
      diester isomers 1,2-di-(2-ethylhexyl) trimellitate (1,2-DEHTM), 1,4-di-(2
      ethylhexyl) trimellitate (1,4-DEHTM) and 2,4-di-(2-ethylhexyl) trimellitate (2,4
      DEHTM) was investigated by a newly developed in vitro experimental design using
      porcine liver esterase (PLE). The substrates were incubated with PLE for 48h at
      25 degrees C in borate buffer and samples were taken at predetermined intervals
      during the experiment. The samples were processed using liquid-liquid extraction
      and analyzed using LC-MS/MS. The results demonstrated a rapid and extensive
      hydrolysis of the diester DEHP to the monoester mono-(2-ethylhexyl) phthalate
      (MEHP) during the incubation with PLE. The isomers of DEHTM were also hydrolyzed
      by PLE to a high extent, whereas TEHTM showed a high stability against enzymatic
      hydrolysis. The regioselective analysis revealed that the monoester isomers 1
      MEHTM and 2-MEHTM were predominantly produced during the degradation of DEHTM
      isomers, indicating a preferred hydrolysis at the para-position. These findings
      are eminent for planning further investigations on the human TEHTM metabolism, as
      the extent, rate and route of metabolism are of crucial importance for a
      toxicological assessment.

PMID- 29180040
TI  - Assessment of test method variables for in vitro skin irritation testing of
      medical device extracts.
AB  - Skin irritation is an important component of the biological safety evaluation of
      medical devices. This testing has typically been performed using in vivo models.
      However, in an effort to reduce the need for in vivo testing, alternative methods
      for assessing skin irritation potential in vitro have been developed using a
      Reconstructed Human Epidermis (RhE) model. During the development of the protocol
      for the round robin validation of in vitro irritation testing for medical device
      extracts, it became clear that there were three points in the procedure where
      different options may be validated within each laboratory for routine testing:
      sample exposure time (18 vs 24h), SDS positive control concentration, and
      cytokine (IL-1alpha) release testing. The goal of our study was to evaluate the
      effect of these variables. EpiDermTM tissues were exposed to extracts of three
      plain polymer samples, and four polymers embedded with known irritant chemicals.
      Exposures were performed for 18 and 24h. Resulting tissue viability was assessed
      by MTT reduction and IL-1alpha release was assessed by ELISA. Testing was also
      performed using various concentrations of SDS ranging from 0.5 to 1% (w/v).
      Overall, results were similar for samples tested and 18 and 24h, but the 18h
      exposure time has the potential to have an impact on the results of some sample
      types. IL-1alpha testing was shown to be useful to clarify conflicting tissue
      viability results. Use of a lower concentration of SDS as a positive control can
      help prevent issues that arise from excessive tissue damage often caused by 1%
      SDS.

PMID- 29180041
TI  - Moving Character Displacement beyond Characters Using Contemporary Coexistence
      Theory.
AB  - Character displacement is one of the most studied phenomena in evolutionary
      biology, yet research has narrowly focused on demonstrating whether or not
      displacement has occurred. We propose a new experimental approach, adopted from
      the coexistence literature, that directly measures interspecific competition
      among sympatric and allopatric populations of species. Doing so allows increased
      ability to (i) test predictions of character displacement without biases inherent
      to character-centric tests, (ii) quantify its effect on the stability of
      coexistence, (iii) resolve the phenotypic pathways through which competitive
      divergence is achieved, and (iv) perform comparative tests. Our approach extends
      research to forms of character displacement not readily identified by past
      methods and will lead to a broader understanding of its consequences for
      community structure.

PMID- 29180042
TI  - In vitro and in vivo anti-malignant melanoma activity of Alocasia cucullata via
      modulation of the phosphatase and tensin homolog/phosphoinositide 3-kinase/AKT
      pathway.
AB  - Alocasia cucullata, a Chinese herb, has been used as an anticancer treatment in
      southern China. Phosphatase and tensin (PTEN), is a tumor suppressor gene and the
      loss of PTEN expression may activate the phosphoinositide-3-kinase (PI3K)/AKT
      signaling pathway which play a key role in tumors formation and progression. In
      this study, we evaluated the anti-melanoma effect and the underlying mechanism of
      50% ethanolic extract of A. cucullata (EAC) in vitro and in vivo. Using MTT,
      wound healing, and transwell assays, we found that EAC suppressed the
      proliferation, migration, and invasion of melanoma cells (B16-F10, A375 and
      A2058) in a dose-dependent manner. We also found that EAC suppresses B16-F10
      tumor growth in a xenografted mouse model. Western blot analysis revealed that
      the expression level of PTEN was up-regulated, and phosphorylation of PI3K and
      AKT reduced in B16-F10 cells and tumor tissues after EAC treatment. No
      significant differences were observed in PI3K and AKT expression. Moreover,
      immunohistochemistry showed that the number of PTEN-positive cells in tumor
      tissues increased and that of p-AKT-positive cells decreased with EAC treatment,
      corroborating the western blot results. Our data reveal that EAC can inhibit
      malignant melanoma in vitro and in vivo and suggest that its anti-tumor effect is
      associated with modulation of the PTEN/ PI3K/AKT signaling pathway. In summary,
      our findings highlight a promising herbal remedy for the treatment of malignant
      melanoma, which warrants further study.

PMID- 29180043
TI  - Isolation and pharmacological characterization of a new cytotoxic L-amino acid
      oxidase from Bungarus multicinctus snake venom.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bungarus multicinctus snake belongs to Elapidae
      family and is widely distributed in southern China. It is widely used in
      traditional Chinese medicine with the effect of dispelling wind and removing
      obstruction in the meridians. Moreover, it is also as a chief ingredient of many
      polyherbal formulations for the treatment of cancer. AIM OF THE STUDY: To
      evaluate the antitumor activity of Bungarus multicinctus snake venom components
      and isolate, characterize the most effective anti-tumor component of Bungarus
      multicinctus snake venom. MATERIALS AND METHODS: The in vitro antitumor activity
      of Bungarus multicinctus venom components was detected by cytotoxicity assay and
      cell apoptosis assay. A unique LAAO from Bungarus multicinctus venom named as BM
      Apotxin was isolated and characterized by Sephadex G-75 gel filtration, Sephadex
      G-25 desalting, Q ion-exchange chromatography and subsequent amino acids sequence
      determination. The LAAO activity and enzyme kinetics of BM-Apotxin was detected
      by microplate assay. RESULTS: BM-Apotxin, a 65KDa glycoprotein, which contributed
      to the most anti-tumor effects of Bungarus multicinctus venom. BM-Apotxin can
      selectively kill tumor cells, with less cytotoxicity to the normal cells. BM
      Apotxin is an L-amino acid oxidase (LAAO) with high sequence identity to other
      snake venom LAAOs. Its anti-tumor activity is mainly due to the hydrogen peroxide
      produced from LAAO oxidation. But the catalase did not reverse its anti-tumor
      effect completely. Like other snake venom LAAOs, BM-Apotxin can oxidize many L
      amino acids, not D amino acids. The optimum substrate for BM-Apotxin is L-Phe.
      Moreover, BM-Apotxin deglycosylation can significantly reduce the LAAO activity
      and anti-tumor activity of BM-Apotxin. CONCLUSION: This study will facilitate the
      study on anti-tumor mechanism of snake venom and drug development based on
      Bungarus multicinctus venom.

PMID- 29180045
TI  - Unraveling the human protein atlas of metastatic melanoma in the course of
      ultraviolet radiation-derived photo-therapy.
AB  - : To explore the photo-therapeutic capacity of UV radiation in solid tumors, we
      herein employed an nLC-MS/MS technology to profile the proteomic landscape of
      irradiated WM-266-4 human metastatic-melanoma cells. Obtained data resulted in
      proteomic catalogues of 5982 and 7280 proteins for UVB- and UVC-radiation
      conditions, respectively, and indicated the ability of UVB/C-radiation forms to
      eliminate metastatic-melanoma cells through induction of synergistically
      operating programs of apoptosis and necroptosis. However, it seems that one or
      more WM-266-4 cell sub-populations may escape from UV-radiation's photo-damaging
      activity, acquiring, besides apoptosis tolerance, an EMT phenotype that likely
      offers them the advantage of developing resistance to certain chemotherapeutic
      drugs. Low levels of autophagy may also critically contribute to the selective
      survival and growth of UV-irradiated melanoma-cell escapers. These are the cells
      that must be systemically targeted with novel therapeutic schemes, like the one
      of UV radiation and Irinotecan herein suggested to be holding strong promise for
      the effective treatment of metastatic-melanoma patients. Given the dual nature of
      UV radiation to serve as both anti-tumorigenic and tumorigenic agent, all
      individuals being subjected to risk factors for melanoma development have to be
      appropriately informed and educated, in order to integrate the innovative PPPM
      concept in their healthcare-sector management. SIGNIFICANCE: This study reports
      the application of nLC-MS/MS technology to deeply map the proteomic landscape of
      UV-irradiated human metastatic-melanoma cells. Data bioinformatics processing led
      to molecular-network reconstructions that unearthed the dual nature of UV
      radiation to serve as both anti-tumorigenic and tumorigenic factor in metastatic
      melanoma cellular environments. Our UV radiation-derived "photo-proteomic" atlas
      may prove valuable for the identification of new biomarkers and development of
      novel therapies for the disease. Given that UV radiation represents a major risk
      factor causing melanoma, a PPPM-based life style and clinical practice must be
      embraced by all individuals being prone to disease's appearance and expansion.

PMID- 29180044
TI  - Cell intrinsic characteristics of human cord blood naive CD4T cells.
AB  - It has been generally considered that the perinatal immune system is less
      inflammatory compared to the adult system and type 2 responses predominate
      perinatal immune responses against antigens. Indeed, previous studies in mice
      showed that there are cell-intrinsic differences between neonatal and adult CD4T
      cells. However, studies on human cord blood and infant blood demonstrated that
      human perinatal T cells do not produce elevated levels of Th2 cytokines with the
      exception of IL-13. These data raise the question if human T cells in the
      perinatal blood fundamentally differ from adult T cells. To decipher differences
      between human perinatal and adult T cells, we performed a focused comparative
      analysis on purified naive CD4T cells from umbilical cord blood (UCB) and adult
      peripheral blood. Our data demonstrate naive CD4T cells from UCB differ from
      adult naive CD4T cells in surface expression of CD26, dipeptidyl peptidase-4.
      While only a fraction of effector/memory T cells from adult blood express CD26,
      practically all T cells from UCB express high levels of CD26. We also determined
      that Th1/Th2 polarizing conditions induce UCB CD4T cells to produce higher levels
      of IFN-gamma and IL-5 compared to adult CD4T cells, respectively. These data
      demonstrate intrinsic differences between UCB and adult naive CD4T cells and
      suggest that human perinatal immune responses involve more complex mechanisms
      than the previously thought Th2-dominant responses.

PMID- 29180046
TI  - Proteomics in cardiovascular diseases: Unveiling sex and gender differences in
      the era of precision medicine.
AB  - : Cardiovascular diseases (CVDs) represent the most important cause of mortality
      in women and in men. Contrary to the long-standing notion that the effects of the
      major risk factors on CVD outcomes are the same in both sexes, recent evidence
      recognizes new, potentially independent, sex/gender-related risk factors for
      CVDs, and sex/gender-differences in the clinical presentation of CVDs have been
      demonstrated. Furthermore, some therapeutic options may not be equally effective
      and safe in men and women. In this context, proteomics offers an extremely useful
      and versatile analytical platform for biomedical researches that expand from the
      screening of early diagnostic and prognostic biomarkers to the investigation of
      the molecular mechanisms underlying CDVs. In this review, we summarized the
      current applications of proteomics in the cardiovascular field, with emphasis on
      sex and gender-related differences in CVDs. SIGNIFICANCE: Increasing evidence
      supports the profound effect of sex and gender on cardiovascular physio-pathology
      and the response to drugs. A clear understanding of the mechanisms underlying
      sexual dimorphisms in CVDs would not only improve our knowledge of the etiology
      of these diseases, but could also inform health policy makers and guideline
      committees in tailoring specific interventions for the prevention, treatment and
      management of CVDs in both men and women.

PMID- 29180047
TI  - Iron status and oxidative stress in the aged rabbit heart.
AB  - Altered iron status may be relevant to the pathophysiology of aging. We have
      assessed redox-active catalytic low molecular weight iron (LMWI), non-heme iron
      (NHI), heme iron (HI), and total iron (TI) in the aerobically perfused hearts of
      aged rabbits (AR, about 4.5years old) and young adult control rabbits (YACR, 3
      4months old); myocardial lipid and protein oxidations were also assessed as
      oxidative stress biomarkers. The levels of LMWI and NHI, as well as of lipid and
      protein oxidation, were higher, while HI content was lower, in the hearts of AR
      than in those of YACR; TI did not differ significantly between the two groups.
      Together with these findings, hemodynamic dysfunction, namely heightened end
      diastolic pressure (EDP) and lowered coronary flow (CF), occurred in the AR
      hearts. Notably, such pattern of hemodynamic dysfunction associated with
      myocardial oxidant damage occurred in the hearts of other YACR perfused in the
      presence of a cell-permeable form of iron, i.e., the iron/hydroxyquinoline
      complex, pointing to the involvement of catalytic iron in the aged heart damage.
      Moreover, as shown in other AR, heart perfusion in the presence of the iron
      chelator deferoxamine (0.6mM or 3.6mM) reduced the myocardial levels of LMWI,
      without significantly affecting those of NHI, HI, and TI; concomitantly, in AR
      deferoxamine lowered myocardial lipid and protein oxidation, and reduced EDP with
      a tendency to augment CF. Instead, deferoxamine, even at high concentration of
      3.6mM, had no significant effects in the YACR. In conclusion, altered iron status
      with catalytic LMWI burden occurs in the aged rabbit heart, eventually resulting
      in iron-dependent cardiac oxidative stress and hemodynamic dysfunction.

PMID- 29180049
TI  - Self-assembled supramolecular hydrogels formed by biodegradable PLA/CS diblock
      copolymers and beta-cyclodextrin for controlled dual drug delivery.
AB  - The supramolecular hydrogel based on inclusion complexation between PLA/CS
      diblock copolymer and beta-CD has been demonstrated. The PLA/CS diblock copolymer
      confirmed by FIIR and 1HNMR were synthesized by in situ polymerization. The
      supramolecular hydrogel formed due to the complexation of PLA/CS with beta
      cyclodextrin was demonstrated by XRD and FIIR analysis. These results indicate
      that the carbonyl groups of PLA can form hydrogen bonds with the hydroxyl groups
      of beta-CD and CS in the complexes. The supramolecular hydrogel presented a
      porous network structure observed by positive fluorescence microscopy (PFM) was
      found to be thixotropic and reversibl. The gel kinetics has been studied by
      monitored the viscosity of the supramolecular system, which was well illustrated
      according to the Stokes-Einstein equation. The in vitro release kinetics studies
      of the two model drug from the hydrogel show the co-encapsulation of heparin
      sodium (HPS) and bovine serum albumin (BSA) exhibits better sustained release
      behaviors. Furthermore, the release rate of HPS is lower than that of BSA was
      explored by the two-dimensional UV correlation spectroscopy. The supramolecular
      hydrogel can be formulated to be a promising candidate for controlled dual drug
      delivery systems.

PMID- 29180048
TI  - Proteolytic and amylolytic enzymes from a newly isolated Bacillus mojavensis SA:
      Characterization and applications as laundry detergent additive and in leather
      processing.
AB  - The present work aims to study the simultaneous production of highly alkaline
      proteases and thermostable alpha-amylases by a newly isolated bacterium Bacillus
      mojavensis SA. The optimum pH and temperature of amylase activity were 9.0 and 55
      degrees C, respectively, while those of the proteolytic activity were 12.0 and 60
      degrees C, respectively. Both alpha-amylase and protease enzymes showed a high
      stability towards a wide range of pH and temperature. Furthermore, SA crude
      enzymes were relatively stable towards non-ionic (Tween 20, Tween 80 and Triton X
      100) and anionic (SDS) surfactants, as well as oxidizing agents. Both activities
      were improved by the presence of polyethylene glycol 4000 and glycerol.
      Additionally, the crude enzymes showed excellent stability against various solid
      and liquid detergents. Wash performance analysis revealed that the SA crude
      enzymes exhibited a remarkable efficiency in the removal of a variety type of
      stains, such as blood, chocolate, coffee and oil. On the other side, SA proteases
      revealed a potential dehairing activity of animal hide without chemical
      assistance or fibrous proteins hydrolysis. Thus, considering their promising
      properties, B. mojavensis SA crude enzymes could be used in several
      biotechnological bioprocesses.

PMID- 29180050
TI  - Potential of Potentilla inclinata and its polyphenolic compounds in alpha
      glucosidase inhibition: Kinetics and interaction mechanism merged with docking
      simulations.
AB  - In the present study we aimed to identify the alpha-glucosidase enzyme inhibitory
      potential of Potentilla inclinata Vill. MeOH and n-BuOH extracts which possessed
      remarkable alpha-glucosidase enzyme inhibitory effects with IC50 values of 1.06+/
      0.02 and 0.93+/-0.01MUg/ml respectively, compared to that of acarbose (IC50
      31.92+/-0.17). Thus, BuOH extract was chosen for further phytochemical
      investigations. A phenolic acid, six flavonol glycosides, and two hydrolysable
      tannins were isolated from the most active n-BuOH extract of the title plant.
      Structures of the isolated compounds were elucidated by 1D- and 2D-NMR
      experiments. All the compounds exhibited remarkable alpha-glucosidase inhibitory
      activity compared to the positive control, acarbose. Rutin (2) showed the highest
      activity with an IC50 value of 26.31+/-0.02MUg/ml. An enzyme kinetics analysis
      revealed that compounds 5 and 7 were competitive, 4 and 6 noncompetitive, and 3
      was uncompetitive inhibitors of alpha-glucosidase enzyme. Molecular docking
      studies were performed to get insights into inhibition mechanisms of the isolates
      considering their inhibition type using various binding sites of the enzyme model
      we previously reported.

PMID- 29180051
TI  - Aptamer based assay of plated-derived grow factor in unprocessed human plasma
      sample and MCF-7 breast cancer cell lysates using gold nanoparticle supported
      alpha-cyclodextrin.
AB  - Platelet-derived growth factor (PDGF), a protein biomarker, is directly involved
      in many cell transformation processes, such as tumor growth and progression.
      Elevation platelet-derived growth factor (PDGF-BB) concentration in plasma could
      indicate the accelerating growth of metastatic breast tumors and angiogenesis.
      The development of an apta-assay for detection of PDGF-BB in is presented in this
      work. A highly specific DNA-aptamer, selected to PDGF-BB was immobilized onto a
      gold nanoparticles supported alpha-cyclodextrin and electrochemical measurements
      were performed in a solution containing the phosphate buffer solution with
      physiological pH. Variety of shapes of gold nanostructures with different sizes
      from zero-dimensional nanoparticles to spherical structures were prepared by one
      step template (alpha-cyclodextrin)-assistant green electrodeposition method.
      Fully electrochemical methodology was used to prepare a new transducer on a gold
      surface which provided a high surface area to immobilize a high amount of the
      aptamer. The surface morphology of electrode was characterized by high-resolution
      field emission scanning electron microscope (FE-SEM) and energy dispersive
      spectroscopy (EDX). The prepared aptasensors represented different
      electrochemical activities toward the redox processes of PDGF-BB attributing to
      the size and shape of the gold nanoparticles. The aptasensor was employed for the
      detection of PDGF using square wave voltammetry (SWV) and Cyclic voltammetry (CV)
      techniques. Under optimized condition the calibration curve for PDGF-BB was
      linear in 0.52-1.52nM with low limit of quantification of 0.52nM. Also, under the
      optimized experimental conditions, the proposed aptasensor of GNPs-cubic-alpha-CD
      Apt-Au electrode exhibited excellent analytical performance for MCF-7 cells
      determination, ranging from 328 TO 593 cells mL-1 with low limit of
      quantification of 328 cells mL-1. As a result, the electrochemical aptasensor was
      able to detect cancer-related targets in unprocessed human plasma samples.

PMID- 29180052
TI  - Evaluation of thiazolidinone derivatives as a new class of mushroom tyrosinase
      inhibitors.
AB  - Tyrosinase (EC 1.14.18.1) is a key copper-containing metalloenzyme widely
      distributed in nature and plays determinant role in melanin biosynthesis. The
      enzyme manifests two unusual catalytic properties including oxidase and
      monooxygenase activities. Its inhibitors may be applied to efficiently treat of
      hyperpigmentation and widely used in pharmaceutical and cosmetic products, as
      well as food supplements and insecticides. The present study aims to evaluate the
      inhibitory effects of some novel azo-hydrazone tautomeric dyes (4a-e) including
      bioactive thiazolidinone moiety on the activity of the mushroom tyrosinase. When
      L-3,4-dihydroxyphenylalanine (L-Dopa) was used as the substrate for the enzyme,
      the compounds 4d, 4a, and 4e showed strong inhibitory effects against the
      activity of the enzyme (61%, 56%, and 49% inhibition in the presence of 60MUM of
      each compound, respectively). The IC50 values of the synthetized compounds were
      measured and their inhibition properties were also visualized by zymography.
      According to tyrosinase inhibitory activity, the compounds 4a, 4c, 4d and 4e
      exhibited strong inhibitory activities with IC50 values of 45.83, 140.25, 37.59,
      and 42.31MUM, respectively, compared to the positive control kojic acid
      (29.44MUM). Kinetic study of 4d compound (as the most potent inhibitor) revealed
      that the compound acts as a reversible competitive inhibitor of the enzyme with
      the Ki value of 31.0MUM. We also simulated the molecular docking with the
      compound 4d and the results confirmed that the compound strongly interacts with
      the mushroom tyrosinase residues. All results totally suggest that thiazolidine
      derivatives, especially 4d, 4a, and 4e, can be considered as safe and efficient
      tyrosinase inhibitors. They also have the potential to be used in the correspond
      fields.

PMID- 29180053
TI  - Unique properties of arginase purified from camel liver cytosol.
AB  - Arginase (ARG) is an enzyme involved in urea cycle, where it catalyzes the
      hydrolysis of L-arginine into L-ornithine and urea. Since there is no information
      about the isolation and purification of ARG from camel liver, this investigation
      was designed to purify and characterize ARG from camel liver and compare its
      molecular and kinetic properties with that reported from other species. Camel
      liver arginase (CL-ARG) was purified to homogeneity using heat denaturation
      followed by ammonium sulphate precipitation with a combination of DEAE-cellulose,
      SP-Sepharose and Sephadex G 100-120 chromatography columns. The specific activity
      of CL-ARG was increased to 18,485 units/mg proteins with 23.5-fold purification
      over crude homogenate. It was observed that CL-ARG showed a similarity with other
      species such as behaviour on DEAE-cellulose column, kinetics of inhibition,
      necessity for metal ions as cofactor, and alkaline optimum pH. On the contrary,
      CL-ARG differed in its molecular weight (180kDa), oligomeric protein structure,
      slightly neutral-alkaline pI value (7.7), Km value (7.1mM), optimum pH (9, 10.7),
      and higher optimum temperature (70 degrees C). In conclusion, this study
      investigated the properties of CL-ARG via a simple and reproducible purification
      procedure and provided valuable information for its production from available
      source in Egypt for medical and industrial purposes.

PMID- 29180054
TI  - [A therapeutic education program for parents of children with ASD: Preliminary
      results about the effectiveness of the ETAP program].
AB  - Autism Spectrum Disorders (ASD) are characterized by particularities of cognitive
      and socio-adaptive functioning. Daily, they require specific interventions for
      the disabled person as well as support for parents who often report deterioration
      in their physical and mental health. To this end, the latest Autism Plan 2013
      2017 highlights the need "to help families to be present and active alongside
      their loved ones, to avoid situations of exhaustion and stress and to enable them
      to play their role fully in the long term". The support devices must therefore be
      based on an analysis of the parents' needs and propose multiple intervention
      modalities, which respond to the complexity of the caregiving mission.
      Therapeutic education (TE) seems to answer to these different elements by
      proposing a global approach improving the development of child-centered skills
      and the educational challenges (self-care skills) but also of skills centered on
      the projects and the fulfillment of the parent (psychosocial skills). The ETAP
      (Therapeutic Education Autism and Parenting) program is an initial TE offer
      intended for parents of children with ASD aged between 3 and 10years. It consists
      of seven group sessions and two semi-structured interviews, called educational
      diagnosis. A booster session is also proposed three months after the last
      session. It was developed following rigorously the guidelines on program
      construction, published by the High Authority of Health. In addition, it is based
      on an assessment of the needs of the parents, an in-depth analysis of the
      literature and the opinion of nine experts in this area. The objective of this
      study is to evaluate the effectiveness of the ETAP program on the quality of life
      and anxio-depressive symptoms of parents of a child with ASD. To our knowledge,
      the ETAP program is the first TE program in France for parents of children with
      an ASD that has been evaluated. Our sample is composed of 40 participants,
      including 30 parents who participated in the ETAP program ("ETAP Group"),
      compared to ten controls who did not participate, but who are on a waiting list
      ("Control Group"). Each participant completed a Quality of Life Questionnaire
      (WhoQol-Brief) and an Anxiety-Depressive Symptomatology Questionnaire (HADS)
      prior to the start of the program (T1) and after the session 7 (T2). Preliminary
      analyses show a good intergroup matching on socio-demographic and medical data.
      Moreover, the two groups are not significantly different at T1 over the set of
      dependent variables measured. Our results show an improvement in the quality of
      life of the depressive symptomatology in the participants. On the other hand, we
      did not notice any significant decrease in anxiety symptoms. However, when we
      consider the proportion of parents with a significant anxiety state (in terms of
      the clinical threshold of HADS, score >=10), we see that it tends to decrease
      after the program only for the group ETAP. These data should be interpreted with
      caution because of their preliminary nature and the small size of our sample.
      However, the first steps are encouraging and confirm the value of the therapeutic
      education model for parents of children with ASD. The different information given
      during the sessions takes into account the previous representations, knowledge
      and skills of the parent. Thus the program promotes the upholding and the
      development of individual resources in parents. In addition, the psychosocial
      skills targeted also to make access easier to available environmental resources.
      Finally, in a more indirect way, the ETAP program also aims to maintain or
      restore a positive parenthood and individual identity and the progressive
      development of new ways of to interact with the environment. An adaptation of the
      Hobfoll resource conservation model is proposed by the authors to formulate
      hypotheses on the mechanisms of action of the ETAP program.

PMID- 29180055
TI  - UPRmt coordinates immunity to maintain mitochondrial homeostasis and animal
      fitness.
AB  - Proper function of mitochondria is often challenged by intrinsic factors and
      extrinsic stimuli. To cope with mitochondrial stress, organisms evolve
      mitochondrial unfolded protein response (UPRmt) to monitor mitochondrial function
      and induce the transcription of mitochondrial chaperones and proteases to restore
      mitochondrial proteostasis and alleviate stress. Interestingly, UPRmt also
      induces immune response genes and improves animals' fitness against pathogen
      infection. In this review, we will summarize progresses of UPRmt studies and
      discuss the relationship between UPRmt and the induction of innate immunity.

PMID- 29180056
TI  - Controversy and debate on dengue vaccine series-paper 1: review of a licensed
      dengue vaccine: inappropriate subgroup analyses and selective reporting may cause
      harm in mass vaccination programs.
AB  - Severe life-threatening dengue fever usually occurs when a child is infected by
      dengue virus a second time. This is caused by a phenomenon called antibody
      dependent enhancement (ADE). Since dengue vaccines can mimic a first infection in
      seronegative children (those with no previous infection), a natural infection
      later in life could lead to severe disease. The possibility that dengue vaccines
      can cause severe dengue through ADE has led to serious concern regarding the
      safety of mass vaccination programs. A published meta-analysis addressed this
      safety issue for a new vaccine against dengue fever-Dengvaxia. The trials in this
      meta-analysis have been used to campaign for mass vaccination programs in
      developing countries. We discuss the results of this paper and point out problems
      in the analyses. Reporting the findings in an Asian trial (CYD14), the authors
      show a sevenfold rise in one outcome-hospitalization for dengue fever in children
      <5 years old. However, they fail to point out two signals of harm for another
      outcome-hospitalization for severe dengue fever (as confirmed by an independent
      data monitoring committee): 1. In children younger than 9 years, the relative
      risk was 8.5 (95% confidence interval [CI]: 0.5, 146.8), and 2. In the overall
      study group, the relative risk was 5.5 (95% CI: 0.9, 33). The authors conduct a
      subgroup analysis to support claims that the vaccine is probably safe among
      children aged 9 years or more. This subgroup analysis has limited credibility
      because: (1) it was a post hoc analysis; (2) it was one of a large number of
      subgroup analyses; (3) the test of interaction was not reported, but was
      insignificant (P = 0.14); and (4) there is no biological basis for a threshold
      age of 9 years. The more likely explanation for the higher risk in younger
      children is ADE, that is, more frequent seronegativity, rather than age itself.
      The selective reporting and inappropriate subgroup claims mask the potential harm
      of dengue mass vaccination programs. Countries planning public use of the vaccine
      must conduct diligent postmarketing surveillance, secure informed consent from
      parents of potential recipients, and closely monitor the results of ongoing long
      term follow-up of clinical trial participants.

PMID- 29180057
TI  - Do Live Discharge Rates Increase as Hospices Approach Their Medicare Aggregate
      Payment Caps?
AB  - CONTEXT: The rate of live discharge from hospice and the proportion of hospices
      exceeding their aggregate caps have both increased for the last 15 years,
      becoming a source of federal scrutiny. The cap restricts aggregate payments
      hospices receive from Medicare during a 12-month period. The risk of repayment
      and the manner in which the cap is calculated may incentivize hospices coming
      close to their cap ceilings to discharge existing patients before the end of the
      cap year. OBJECTIVE: The objective of this work was to explore annual cap-risk
      trends and live discharge patterns. We hypothesized that as a hospice comes
      closer to exceeding its cap, a patient's likelihood of being discharged alive
      increases. METHODS: We analyzed monthly hospice outcomes using 2012-2013 Medicare
      claims. RESULTS: Adjusted analyses showed a positive and statistically
      significant relationship between cap risk and live discharges. CONCLUSION:
      Policymakers ought to consider the unintended consequences the aggregate cap may
      be having on patient outcomes of care.

PMID- 29180058
TI  - Integration of Complementary Medicine in Supportive Cancer Care: A Call for
      Middle-Eastern Collaborative Research.

PMID- 29180059
TI  - End-of-Life Care in Imprisoned Persons.

PMID- 29180060
TI  - Forgotten Influences and Reflections on Exercise and on the End of the Year 2017.

PMID- 29180061
TI  - HPLC and in vitro evaluation of antioxidant properties of fruit from Malpighia
      glabra (Malpighiaceae) at different stages of maturation.
AB  - Malpighia glabra L. is indicated for the treatment of diseases due presenting
      several medicinal properties. The aim of the present study was quantify phenolic
      compounds and carotenoids, additionally, evaluate the antioxidant potential of
      different methanolic fractions (mature stage, intermediate stage and green
      maturity stage) of Malpighia glabra. Methanolic fractions of the three stages of
      maturation were characterized using HPLC-DAD. The antioxidant activity of
      fractions was evaluated using in vitro assay systems: iron-chelating activity
      (Fe2+), inhibition of the radical 1-1-diphenyl-2-picrylhydrazyl (DPPH) and
      inhibition of production of thiobarbituric acid reactive substances (TBARS). In
      quantifying compounds by HPLC-DAD showed that the compounds rutin and quercetin
      showed the highest peaks in the three samples tested. Regarding carotenoids, the
      beta-carotene stood in the analyze. The methanolic fraction of lyophilized pulp
      of green fruits showed better results for iron chelation and DPPH tests; TBARS by
      the methanolic fraction of the ripe fruits showed lower IC50 as the basal. When
      in the presence of iron as an inducer of peroxidation, the methanolic fraction of
      the pulp of green fruits showed the lowest IC50. Our research indicates that the
      o fruits of M. glabra good potential in scavenging free radicals and can be an
      important source of antioxidant phytochemical.

PMID- 29180062
TI  - Metabolic detoxification of bakuchiol is mediated by oxidation of CYP 450s in
      liver microsomes.
AB  - Bakuchiol, one of bioactive compounds isolated from the dried ripe fruits of
      Psoralea corylifolia L., possesses a variety of pharmacological activities. In
      this study, the metabolites of bakuchiol in rat liver microsomes as well as their
      cytotoxicities were studied. A total of eight metabolites were isolated and
      identified as 14-carboxylbakuchiol (M1), 14,15-dihydroxybakuchiol (M2), 12,13
      dihydroxybakuchiol (M3), 15-hydroxybakuchiol (M4), 14-hydroxybakuchiol (M5),
      bakuchiol hydrate (M6), 15-hydroxybakuchiol acetate (M7), and 14-hydroxybakuchiol
      acetate (M8). All the metabolites are new compounds except for M3. The main type
      of biotransformation is oxidation reaction, including hydroxylation, epoxidation
      and carboxylation. Cytotoxicities of bakuchiol and its metabolites against human
      kidney-2 (HK-2) cell line were evaluated. The median inhibition concentration
      (IC50) values of bakuchiol, M4, M6 and M8 were (29.48 +/- 0.22) MUM, (67.51 +/-
      6.80) MUM, (90.23 +/- 3.89) MUM, and (86.62 +/- 6.08) MUM, respectively, and the
      IC50 values of M1, M2, M3, M5, and M7 were all in excess of 100 MUM. To further
      verify the metabolic reliability, the metabolits of bakuchiol in vivo and the
      metabolic species variations in human and rat liver microsomes were studied using
      UPLC-MS/MS method. This study provides valuable information for further
      investigation of metabolism and toxicity of bakuchiol in vivo.

PMID- 29180063
TI  - Letter to the Editor in response to "Our unrequited love for natural
      ingredients," by Burdock and Wang.
AB  - This letter is in response to the review article "Our unrequited love for natural
      ingredients" authored by Burdock and Wang in the September edition of FCT. Our
      purpose is to clarify the procedure used by the FEMA Expert Panel for the safety
      evaluation of natural flavor complexes, as well as to note and/or correct
      inaccuracies that we have identified within the article.

PMID- 29180064
TI  - Exposure to bisphenol S alters the expression of microRNA in male zebrafish.
AB  - Bisphenol S (BPS), an alternative compound of bisphenol A, has been found to
      affect reproduction, development, and immune system. Although microRNAs (miRNAs)
      play an important role in many metabolic activities, whether and how they are
      involved in the process of BPS-induced toxicity is unknown. In the present study,
      BPS-induced changes in miRNAs and target gene expression in male zebrafish gonad,
      and the potential mechanism was investigated. Male zebrafish were exposed to 0,
      5, and 50MUg/L BPS for 21 d. miRNA was isolated from the gonad pool and the
      expression profiles of 255 known zebrafish miRNAs were analyzed using
      microarrays. Quantitative real-time polymerase chain reaction was used to
      validate the expression of several miRNAs in the microarray data. The GO term
      analysis revealed that miRNAs significantly affected by BPS exposure were
      involved in hematopoiesis, lymphoid organ development, and immune system
      development. Among 14 miRNAs that were significantly regulated after exposure to
      5 and 50MUg/L BPS, six targeted cyp19a1b gene, suggesting the role of BPS-induced
      toxicity via the interference with the aromatization process. Our findings
      provide novel insight into the epigenetic regulatory mechanisms of BPS-induced
      toxicity in male zebrafish, and identification of novel miRNA biomarkers for
      exposure to BPS.

PMID- 29180065
TI  - beta-Naphthoflavone treatment attenuates neonatal hyperoxic lung injury in wild
      type and Cyp1a2-knockout mice.
AB  - Exposure to supraphysiological concentrations of oxygen (hyperoxia) leads to
      bronchopulmonary dysplasia (BPD), one of the most common pulmonary morbidities in
      preterm neonates, which is more prevalent in males than females. Beta
      naphthoflavone (BNF) is protective against hyperoxic lung injury in adult and
      neonatal wild type (WT) mice and in and mice lacking Cyp1a1gene. In this
      investigation, we tested the hypothesis that BNF treatment will attenuate
      neonatal hyperoxic lung injury in WT and Cyp1a2-/- mice, and elucidated the
      effect of sex-specific differences. Newborn WT or Cyp1a2-/- mice were treated
      with BNF (10mg/kg) or the vehicle corn oil (CO) i.p., from postnatal day (PND) 2
      to 8 once every other day, while being maintained in room air or hyperoxia (85%
      O2) for 14days. Hyperoxia exposure lead to alveolar simplification and arrest in
      angiogenesis in WT as well as Cyp1a2-/- mice No significant differences were seen
      between WT and Cyp1a2-/- mice. Cyp1a2-/- female mice had better preservation of
      pulmonary angiogenesis at PND15 compared to similarly exposed males. BNF
      treatment attenuated lung injury and inflammation in both genotypes, and this was
      accompanied by a significant induction of hepatic and pulmonary CYP1A1 in WT but
      not in Cyp1a2-/- mice. BNF treatment increased NADPH quinone oxidoreductase
      (NQO1) mRNA levels in Cyp1a2-/- mouse livers compared to WT mice. These results
      suggest that BNF is protective in neonatal mice exposed to hyperoxia independent
      of CYP1A2 and this may entail the protective effect of phase II enzymes like
      NQO1.

PMID- 29180066
TI  - Inhibition of estrogen receptor reduces connexin 43 expression in breast cancers.
AB  - Connexins are widely supported as tumor suppressors due to their downregulation
      in cancers, nevertheless, more recent evidence suggests roles for connexins in
      facilitating tumor progression in later stages, including metastasis. One of the
      key factors regulating the expression, modification, stability, and localization
      of connexins is hormone receptors in hormone-dependent cancers. It is reasonable
      to consider that hormones/hormone receptors may modulate connexins expression and
      play critical roles in the cellular control of connexins during breast cancer
      progression. In estrogen receptor (ER)-positive breast cancers, tamoxifen and
      fulvestrant are widely used therapeutic agents and are considered to alter ER
      signaling. In this present study, we investigated the effects of fulvestrant and
      tamoxifen in Cx43 expression, and we also explored the role of Cx43 in ER
      positive breast cancer migration and the relationship between Cx43 and ER. The
      involvement of estrogen/ER in Cx43 modulation was further verified by
      administering tyrosine kinase inhibitors and chemotherapeutic agents. We found
      that inhibition of ER promoted the binding of E3 ligase Nedd4 to Cx43, leading to
      Cx43 ubiquitination. Furthermore, inhibition of ER by fulvestrant and tamoxifen
      phosphorylated p38 MAPK, and inhibition of Rac, MKK3/6, and p38 reversed
      fulvestrant-reduced Cx43 expression. These findings suggest that Cx43 expression
      which may positively regulate cell migration is ER-dependent in ER-positive
      breast cancer cells.

PMID- 29180067
TI  - "Sports Ultrasound", advantages, indications and limitations in upper and lower
      limbs musculoskeletal disorders. Review article.
AB  - Ultrasonography (US) is a safe and noninvasive imaging modality that is gaining
      popularity in different medical and surgical fields. Its introduction in
      musculoskeletal and sports medicine has taken this advanced subspecialty to a
      higher level. It has the advantage over other imaging techniques with regards to
      ease of use, availability, comfort and cost. Not to mention, in terms of safety
      profile, patients are not exposed to radiations, like in x-rays, and it can be
      performed on patients with metal or pacemaker implants, which are contraindicated
      in MRI. Standard diagnostic sonography doesn't have any known harmful effects on
      humans. In this article we will discuss the role of ultrasound in sports
      medicine, highlighting the diagnostic and interventional indications, uses and
      limitations.

PMID- 29180068
TI  - Timing of surgery for aneurysmal subarachnoid hemorrhage: A systematic review and
      meta-analysis.
AB  - INTRODUCTION: The timing of surgery for aneurysmal subarachnoid hemorrhage
      influences the outcome, but the optimal timing remains controversial. We
      conducted a systematic review to clarify whether early surgery was better than
      late surgery for improving outcome. MATERIALS AND METHODS: We systematically
      searched several databases to screen eligible studies. After synthesizing data,
      an overall effect was shown using a risk ratio (RR) and 95% confidence interval
      (CI). Subgroup analyses were stratified by multiple variables to control the
      confounding factors. Sensitivity analyses were applied to check the robustness of
      the results. Publication bias was measured with Egger's and Begg's tests.
      RESULTS: A total of 14 studies were included in the analysis. Compared with late
      surgery, early surgery significantly decreased the incidence of poor outcome,
      regardless of whether patients were in good condition (RR, 0.65 [95%CI, 0.50
      0.84]; p = 0.001) or in poor condition on admission (RR, 0.71 [95%CI, 0.61 0.83];
      p < 0.0001). Moreover, when patients were in good condition on admission, early
      surgery also effectively reduced the death rate (RR, 0.61 [95%CI, 0.46 0.82]; p =
      0.001). Additionally, early surgery reduced the death rate compared with late
      surgery in patients older than 50 years (RR, 0.49 [95%CI, 0.27 0.89]; p < 0.002).
      CONCLUSIONS: Early surgery was superior to late surgery in reducing a poor
      outcome and death rate when patients were in good condition on admission, and
      decreased the incidence of poor outcome when patients were in poor condition on
      admission. Age was a potential confounding factor, influencing the effect of
      early surgery. Further study is required on this issue.

PMID- 29180069
TI  - Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis:
      Time to change the goal of our research?

PMID- 29180071
TI  - Role of thromboxane A2 signaling in endothelium-dependent contractions of
      arteries.
AB  - Thromboxane A2 (TxA2) plays a very important role in various cardiovascular
      diseases through its action on platelet aggregation, vasoconstriction, and
      proliferation. The present article focuses on the role of TxA2 signaling in
      endothelium-dependent contractions of arteries. Arachidonic acid (AA) is
      metabolized by cyclooxygenase (COX) to form the unstable prostaglandin H2 which
      is further converted into TxA2. After being produced by thromboxane synthase
      (TxAS), TxA2 ultimately stimulates TxA2/prostanoid (TP) receptor to induce
      vasoconstriction. The calcium ionophore A23187, the prostanoid precursor AA, or
      the muscarinic receptor agonist acetylcholine (ACh) can evoke endothelium
      dependent contractions associated with TxA2. The endothelium-dependent
      contractions shown in hypertension, diabetes, atherogenesis, and other
      cardiovascular diseases have been significantly reduced by antagonism of COX,
      TxAS, or TP receptor. So inhibition of the bioavailability and/or effect of TxA2
      may be promising therapeutic targets to prevent these diseases. Especially some
      bioactive compounds isolated from medicinal plants will provide new
      pharmacological approaches to promote vascular health.

PMID- 29180072
TI  - Functional Outcome of Completely Intracorporeal Robotic Ileal Ureteric
      Replacement.
AB  - OBJECTIVE: To assess perioperative, clinical, and functional outcomes following
      completely robotic ileal ureter. METHODS: We retrospectively reviewed 7
      consecutive patients undergoing completely intracorporeal ileal ureteric
      replacement between November 2015 and May 2017. One patient had a solitary
      kidney. A 4-arm technique was used. In 5 patients, additional psoas hitch
      procedure was performed. Patients had retrograde filling and removal of the ileal
      stent and transurethral catheter at an average of 14 days postoperatively. Renal
      ultrasonography, serum analysis, and diuretic renography were performed at follow
      up 3 months postoperatively. RESULTS: Mean operative time was 328 +/- 66.3
      minutes and median estimated blood loss was 100 mL (range 50-200); mean length of
      the ileal substitute was 20.4 cm (range 18-24). No case was converted to open
      surgery. In 1 patient, there was a prolonged insufficiency of the pyeloileal
      anastomosis, requiring prolonged stenting. Apart from that, there were no major
      complications and no open surgical or endoscopic reinterventions. On 3-month
      follow-up, all patients presented symptom-free, with no signs of obstruction on
      ultrasound and significantly improved glomerular filtration rate, creatinine
      levels, and differential renal function (P = .02, 0.03, and 0.046, respectively).
      Five patients had a diuretic halftime <10 minutes, 2 had a halftime between 10
      and 20 minutes. CONCLUSION: Completely intracorporeal robotic ileal ureteric
      replacement results in full functional restoration of the upper tract in cases of
      long defects of the mid and upper ureter.

PMID- 29180073
TI  - Assessing the potential impact of a front-of-pack nutritional rating system on
      food availability in school canteens: A randomised controlled trial.
AB  - BACKGROUND: Front-of-pack graphical nutritional rating of products is becoming an
      important strategy in many countries to improve healthy food purchases by
      consumers. Evidence of the effectiveness of such on facilitating healthy food
      choices by school food service providers has not been reported. The primary aim
      of the study was to assess the impact of providing front-of-pack nutritional
      rating information on school canteen managers' likely food selections. Secondary
      outcomes were canteen manager awareness, attitudes and reported barriers to using
      the front-of-pack information. METHODS: A randomised controlled trial involving
      primary school canteen managers was conducted in a single region in New South
      Wales, Australia. Eligible participants were randomised to an intervention or
      control group and asked in a telephone interview which of 12 common food products
      sold in school canteens they would sell. Both groups received product name and
      brand information. The intervention group also received information regarding the
      nutritional rating of products. RESULTS: Canteen managers in the intervention
      group were significantly more likely than those in the control group to indicate
      they would sell three of the six 'healthier' products (p = 0.036, 0.005, 0.009).
      There was no difference between groups in the likelihood of making available for
      sale any of the six 'less healthy' products. The majority of canteen managers who
      had heard of a product nutritional rating system agreed that it was helpful in
      identifying 'healthier' foods (88%, n = 31). CONCLUSIONS: The inclusion of
      product nutritional rating information has the potential to improve the
      availability of some 'healthier' items on canteen menus and contribute to
      improving child dietary intake. Further research is required to determine whether
      the use of product nutritional rating information actually makes a difference to
      canteen manager choices.

PMID- 29180070
TI  - A high-throughput screening campaign to identify inhibitors of DXP
      reductoisomerase (IspC) and MEP cytidylyltransferase (IspD).
AB  - The rise of antibacterial resistance among human pathogens represents a problem
      that could change the landscape of healthcare unless new antibiotics are
      developed. The methyl erythritol phosphate (MEP) pathway represents an attractive
      series of targets for novel antibiotic design, considering each enzyme of the
      pathway is both essential and has no human homologs. Here we describe a pilot
      scale high-throughput screening (HTS) campaign against the first and second
      committed steps in the pathway, catalyzed by DXP reductoisomerase (IspC) and MEP
      cytidylyltransferase (IspD), using compounds present in the commercially
      available LOPAC1280 library as well as in an in-house natural product extract
      library. Hit compounds were characterized to deduce their mechanism of
      inhibition; most function through aggregation. The HTS workflow outlined here is
      useful for quickly screening a chemical library, while effectively identifying
      false positive compounds associated with assay constraints and aggregation.

PMID- 29180074
TI  - Sweet taste of prosocial status signaling: When eating organic foods makes you
      happy and hopeful.
AB  - As the current research suggests that there are links between prosocial acts and
      status signaling (including sustainable consumer choices), we empirically study
      (with three experiments) whether food consumers go green to be seen. First, we
      examine how activating a motive for status influences prosocial organic food
      preferences. Then, we examine how the social visibility of the choice (private
      vs. public) affects these preferences. We found that when consumers' desire for
      status was elicited, they preferred organic food products significantly over
      their nonorganic counterparts; making the choice situation visible created the
      same effect. Finally, we go beyond consumers' evaluative and behavioral domains
      that have typically been addressed to investigate whether this (nonconscious)
      "going green to be seen" effect is also evident at the level of more
      physiologically-driven food responses. Indeed, status motives and reputational
      concerns created an improved senso-emotional experience of organic food.
      Specifically, when consumers were led to believe that they have to share their
      organic food taste experiences with others, an elevation could be detected not
      only in the pleasantness ratings but also in how joyful and hopeful they felt
      after eating a food sample. We claim that the reason for this is that a tendency
      to favor organic foods can be viewed as a costly signaling trait, leading to
      flaunting about one's prosocial tendencies. According to these findings,
      highlighting socially disapproved consumption motives, such as reputation
      management, may be an effective way to increase the relatively low sales of
      organic foods and thereby promote sustainable consumer behavior.

PMID- 29180075
TI  - Cortical neuromodulation for neuropathic pain and Parkinson disease: Where are
      we?
AB  - Cortex neuromodulation is promising approach for treatment of some neurological
      conditions, especially neuropathic pain and Parkinson's disease. Effects of non
      invasive cortical stimulation are short lived; transcranial direct current
      stimulation (tDCS) and transcranial alternating current stimulation (tACS) may be
      useful to assess the suitability for invasive cortical stimulation. Direct
      cortical stimulation (DCS) is the method able to provide long-lasting effects in
      treatment of neuropathic pain and some symptoms of Parkinson's disease through
      the use of totally implantable systems that ensure a chronic stimulation.

PMID- 29180076
TI  - Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal,
      hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO,
      CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG,
      NCRI, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines.
AB  - PURPOSE: Few studies have reported large inter-observer variations in target
      volume selection and delineation in patients treated with radiotherapy for head
      and neck squamous cell carcinoma. Consensus guidelines have been published for
      the neck nodes (see Gregoire et al., 2003, 2014), but such recommendations are
      lacking for primary tumour delineation. For the latter, two main schools of
      thoughts are prevailing, one based on geometric expansion of the Gross Tumour
      Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical
      expansion of the GTV using compartmentalization of head and neck anatomy. METHOD:
      For each anatomic location within the larynx, hypopharynx, oropharynx and oral
      cavity, and for each T-stage, the DAHANCA proposal has been comprehensively
      reviewed and edited to include anatomic knowledge into the geometric Clinical
      Target Volume (CTV) delineation concept. A first proposal was put forward by the
      leading authors of this publication (VG and CG) and discussed with opinion
      leaders in head and neck radiation oncology from Europe, Asia, Australia/New
      Zealand, North America and South America to reach a worldwide consensus. RESULTS:
      This consensus proposes two CTVs for the primary tumour, the so called CTV-P1 and
      CVT-P2, corresponding to a high and lower tumour burden, and which should be
      associated with a high and a lower dose prescription, respectively. CONCLUSION:
      Implementation of these guidelines in the daily practice of radiation oncology
      should contribute to reduce treatment variations from clinicians to clinicians,
      facilitate the conduct of multi-institutional clinical trials, and contribute to
      improved care of patients with head and neck carcinoma.

PMID- 29180077
TI  - Expression of CD133 as a Putative Prognostic Biomarker to Predict Intracranial
      Dissemination of Primary Spinal Cord Astrocytoma.
AB  - OBJECTIVE: Spinal cord astrocytoma with intracranial dissemination carries a poor
      prognosis. The mechanisms leading to dissemination remain to be elucidated. A
      stem cell marker, CD133, was reported to predict recurrence patterns in
      intracranial glioblastoma. We evaluated the significance of CD133 as a putative
      prognostic biomarker to predict intracranial dissemination in spinal cord
      astrocytoma. METHODS: This study included 14 consecutive patients with primary
      spinal cord astrocytoma treated from 1998 to 2014. Six of the patients were women
      and the patients' ages ranged from 12 to 75 years. Seven and 6 patients underwent
      open biopsy and partial resection of the tumors, respectively. After confirmation
      of the histologic diagnoses, all patients were treated with postoperative
      radiotherapy, chemotherapy, or a combination of both. To identify factors
      predictive of intracranial dissemination, we analyzed their clinical data
      including Ki-67 labeling index, and CD133 expression. RESULTS: Intracranial
      dissemination was observed in 6 of 14 patients. All 6 patients died during the
      follow-up period. Of the 8 patients without intracranial dissemination, 5
      survived (P = 0.02). Median survival for the patients with intracranial
      dissemination was 22.7 months. CD133 expression was significantly higher in
      patients with intracranial dissemination (P = 0.04), whereas other variables did
      not indicate the dissemination. CONCLUSIONS: The expression of CD133 can be an
      efficient biomarker to predict intracranial dissemination in spinal cord
      astrocytoma. Recognition of high CD133 expression in surgical specimens and early
      detection of intracranial dissemination is important for the clinical management
      of spinal cord astrocytoma.

PMID- 29180078
TI  - Surgical Orthopedics in a Spondylometaphyseal Dysplastic Patient.
AB  - BACKGROUND: Spondylometaphyseal dysplasia (SMD) is a rare disease characterized
      by vertebral and metaphyseal abnormalities. The treatment of SMD spinal
      deformities remains a challenge for spinal surgeons. The purpose of this study is
      to demonstrate the feasibility and effectiveness of vertebral column resection of
      SMD by thoracolumbar kyphosis and scoliosis. CASE DESCRIPTION: A 23-year-old man
      with SMD was referred to us with multivertebral anomalies and scoliosis, and a
      rigid curved thoracolumbar kyphosis in T11-12. The patient had fixed
      thoracolumbar kyphosis and scoliosis with neurologic symptoms. The morphology of
      vertebra was measured and calculated based on radiologic data. A 3-dimensional
      printing was made to help the spinal orthopedics. The anterior fusion was made
      with cages reconstruction and posterolateral fusion with screw fixation.
      CONCLUSIONS: The spinal axes were corrected with obvious and satisfying
      realignment effects. The neurologic symptoms disappeared after surgery. The 1
      year follow-up period was uneventful. Surgical treatment for SMD multiaxial spine
      malformation is feasible. Posterior column resection with segmental pedicle screw
      fixation and complementary fusion provides obvious curative effects for adult
      patients with neurologic complications.

PMID- 29180079
TI  - Adult Pilocytic Astrocytoma: An Institutional Series and Systematic Literature
      Review for Extent of Resection and Recurrence.
AB  - INTRODUCTION: Pilocytic astrocytoma is a classically benign tumor that most often
      affects pediatric patients. Rarely, it occurs during adulthood. We present a case
      series and systematic literature review of adult pilocytic astrocytoma (APA) to
      examine the clinical presentation, extent of resection, and recurrence rate
      associated with this tumor in this population. MATERIALS AND METHODS: Our
      institutional records were retrospectively reviewed for cases of pilocytic
      astrocytoma in adults. A PubMed search identified English-language studies of
      pathology-proven APA. A meta-analysis was performed to determine the relationship
      between extent of tumor resection and recurrence. RESULTS: Forty-six patients
      with APA were diagnosed at our institution (mean age 33.6 +/- 13.3; 24 [52%]
      female). Twenty-four patients (52%) underwent gross total resection, 11 (24%)
      subtotal resection, 4 (9%) near total resection, 4 (9%) observation after biopsy,
      and 3 (6%) radiotherapy alone. Tumors recurred or progressed in 6 (13%) patients,
      of whom 4 were treated by STR and 2 were treated by radiotherapy alone. Thirty
      nine (95%) patients were still alive at last follow-up. A systematic literature
      review identified 415 patients with APA in 38 studies. Including our case series,
      7 studies reported extent of resection, follow-up, and recurrence. Of 254
      patients with a weighted mean follow-up of 77.7 +/- 49.6 (31-250) months, 129
      (51%) were treated with gross total resection, and 125 (49%) underwent subtotal
      resection. Tumor recurred in 79 (31%) patients, 22 (27%) after gross total
      resection and 57 (73%) after subtotal resection (P < 0.001). CONCLUSIONS:
      Pilocytic astrocytoma rarely presents during adulthood. Overall, prognosis is
      favorable and survival rates are high. APA recurrence is more likely after STR,
      and the goal of surgery should always be GTR when feasible.

PMID- 29180080
TI  - Long-Term Outcome After Carotid Endarterectomy in Patients with Ischemic Heart
      Disease.
AB  - BACKGROUND: The long-term outcome after carotid endarterectomy (CEA) is
      determined by many confounding factors. Ischemic heart disease (IHD) is linked to
      atherosclerotic stroke, and it is an important cause of death during the
      perioperative and follow-up periods after CEA. We aimed to investigate mortality
      and long-term major adverse cardiovascular events (MACEs) in patients with IHD
      compared with patients who do not have IHD. METHODS: We consecutively enrolled
      229 patients who underwent CEA procedures from 2000 to 2011. Of these patients,
      45 had known or probable IHD defined by history or medical record of myocardial
      infarction, stable/unstable angina, previous coronary revascularization such as
      percutaneous coronary intervention or coronary artery bypass graft, or positive
      stress test. Long-term outcome was identified by using death certificates from
      the Korean National Statistical Office and telephone interviews by June 2013. We
      investigated predictors of early (<=30 days) and long-term mortality and MACEs
      (stroke, myocardial infarction, and death). RESULTS: Mean follow-up period was 49
      months. Cox proportional analysis adjusted for potent predictors revealed
      symptomatic stenosis (hazard ratio, 1.72; 95% confidence interval, 1.02-2.88; P =
      0.042) and presence of IHD (hazard ratio, 1.93; 95% confidence interval, 1.09
      3.42; P = 0.025) as significant predictors of long-term MACEs. Kaplan-Meier
      analysis showed a significantly lower rate of survival (P = 0.030) and MACE-free
      survival (P = 0.003) in the IHD group. CONCLUSIONS: In this study, a poor long
      term outcome was observed in patients with IHD and symptomatic stenosis but not
      in patients with conventional high-risk factors for surgery. Therefore,
      appropriate evaluation and treatment of IHD before and after CEA might be helpful
      for better outcome.

PMID- 29180081
TI  - The Patient Size Setting: A Novel Dose Reduction Strategy in Cerebral
      Endovascular Neurosurgery Using Biplane Fluoroscopy.
AB  - BACKGROUND: In some fluoroscopy machines, the dose-rate output of the fluoroscope
      is tied to a selectable patient size. Although patient size may play a
      significant role in visceral or cardiac procedures, head morphology is less
      variable, and high dose outputs may not be necessary even in very obese patients.
      We hypothesized that very small patient size setting can be used to reduce dose
      for cerebral angiography without compromising image quality. METHODS: Patients
      who underwent endovascular neurosurgical procedures during the 2015-2016 academic
      year were identified, and estimated procedural air kerma (AK) was tabulated
      retrospectively. Technologists were instructed to begin using the very small
      patient size setting for all procedures performed using our Philips Allura Xper
      FD20 biplane fluoroscopy system beginning in March 2016. No changes were made in
      a second procedure room using a Toshiba Infinix system. Student t tests and
      logistic regression models were used to compare radiation exposure before and
      after March 1, 2016, for both machines. RESULTS: For diagnostic cerebral
      angiograms performed on the Philips system (n = 302), AK was reduced by
      approximately 17% (1277 vs. 1061 mGy; P = 0.0006.) Changes in table height, total
      fluoroscopy time, patient weight, and body mass index did not contribute to this
      difference. No significant change was seen in total AK using the Toshiba system
      (n = 237). Blinded review by a neuroradiologist did not demonstrate any change in
      image quality. CONCLUSIONS: Using the very small patient size reduces fluoroscopy
      dose by 17% for cerebral angiography without impacting image quality.

PMID- 29180082
TI  - Quantitative Volumetric Analysis Following Magnetic Resonance-Guided Laser
      Interstitial Thermal Ablation of Cerebellar Metastases.
AB  - BACKGROUND: Treating recurrent posterior fossa metastases after previous
      radiation therapy and surgical resection remains challenging. Magnetic resonance
      laser-induced thermal therapy (MR-LITT) is a promising treatment for recurrent
      lesions, but data on safety, efficacy, and postablation volume change in the
      posterior fossa are lacking. METHODS: All patients with recurrent posterior fossa
      metastatic lesions treated with MR-LITT by the senior neurosurgeon were included
      in the study. Preoperative and postoperative follow-up magnetic resonance imaging
      (MRI) studies were used to measure lesional and perilesional edema volume. These
      measurements were compared to calculate percent ablation volume. All patients'
      clinical examinations were followed closely. RESULTS: Four patients with
      recurrent cerebellar metastases were treated with MR-LITT. The average percent
      lesion ablated was 97.1% (range, 88.2%-100%). The average preoperative lesion
      volume was 3.3 cm3 (range, 1.1-7.2 cm3), and the average final postoperative
      volume was 3.8 cm3 (range, 0.5-7.6 cm3). Lesion volume increased to maximum
      volume on postoperative day 1, with an average increase of 486.9%. The
      extrapolated average time for the lesion to shrink to below the initial size was
      294.5 days. There was a trend toward a decrease in average edema volume from the
      preoperative MRI of 17.8 cm3 to final postoperative follow-up MRI of 3.4 cm3 (P =
      0.0952). No postoperative hydrocephalus or complications occurred. CONCLUSIONS:
      This pilot study shows that LITT appears to be a safe and promising treatment for
      recurrent posterior fossa metastatic lesions up to 7.2 cm3. Further randomized
      controlled studies are warranted to further characterize the long-term efficacy
      of this therapy.

PMID- 29180083
TI  - Rupture Resemblance Models May Correlate to Growth Rates of Intracranial
      Aneurysms: Preliminary Results.
AB  - BACKGROUND: Treatment of intracranial aneurysms (IAs) is largely guided by IA
      size and growth. Preliminary investigations have found a relationship between
      clinical factors and growth; yet, the relationship between morphologic and
      hemodynamic risk prediction models in IA growth is unknown. METHODS: We analyzed
      serial images of 5 growing and 6 stable IAs. Rupture resemblance scores (RRSs)
      were calculated from three-dimensional segmented images and computational fluid
      dynamics simulations. The morphologic (RRSM), hemodynamic (RRSH), and combination
      (RRSC) scores leveraged IA size ratio, wall shear stress, and oscillatory shear
      index. Comparisons of RRS and morphologic and hemodynamic characteristics were
      made between growing and stable IAs at the baseline time point and between the
      baseline and follow-up time points of the growing IAs. In addition, we
      investigated the correlation of growth rate and RRS and the hemodynamics of
      growing and stable regions were compared. RESULTS: Our results indicate that
      there is no statistical difference in IAs at the baseline time point; however,
      growing IAs tend to have a higher aspect ratio (P = 0.066), undulation index (P =
      0.086), and RRSC (P = 0.86). In addition, we found a significant correlation
      between growth rate and baseline RRS of all 3 models (RRSM, r = 0.874, P < 0.001;
      RRSH, r = 0.727, P = 0.011; RRSC, r = 0.815, P = 0.002). We also found that
      growing IAs significantly increased in aspect ratio (P = 0.034), size ratio (P =
      0.034), and RRSM (P = 0.034). Our results show that stable and growing regions
      had statistically different wall shear stress and oscillatory shear index.
      CONCLUSIONS: Based on this preliminary study, we conjecture that aneurysms that
      resemble ruptured IAs may grow faster.

PMID- 29180084
TI  - Cerebellar Mutism Syndrome and Other Complications After Surgery in the Posterior
      Fossa in Adults: A Prospective Study.
AB  - BACKGROUND: Cerebellar mutism syndrome (CMS) is rarely described in adults;
      however, data on self-assessed linguistic complications after posterior fossa
      surgery do not exist. METHODS: Through a prospective single-center study, data on
      59 tumor operations in the posterior fossa were collected preoperatively as well
      as 1 week and 1 month postoperatively. Data on self-assessed problems in 5 CMS
      related domains, CMS scores, and neurology as well as surgical procedure and
      complications were obtained. RESULTS: Data on CMS-related complications were
      obtained on 56 of the 59 operations. None was found to have CMS according to the
      CMS score. Within each of the 5 domains, at least 9 operations (16%) were
      followed by development or worsening of self-assessed CMS-related complications.
      Self-assessed complications were found to be most frequent after primary tumor
      surgeries, although they were significant only for speech and motor complications
      (P value = 0.01 and 0.02). Speech and language complications occurred more
      frequently in midline tumors compared with lateral tumors (40% vs. 7%; P =
      0.004). Surgical complications were similar to other studies. CONCLUSIONS: We
      propose that speech and language problems in adults undergoing surgery in the
      posterior fossa occur more frequently than previously assumed. Some of the self
      assessed complications might reflect components of the cerebellar cognitive
      affective syndrome. Our findings are consistent with the fact that midline
      location of the tumor is one of the few known risk factors for CMS in children.
      Thus, the cerebellar midline seems to be a vulnerable region for speech and
      language complications also in adults.

PMID- 29180085
TI  - Transvenous Embolization of Ethmoidal Dural Arteriovenous Fistulas: Case Series
      and Review of the Literature.
AB  - BACKGROUND: Ethmoidal dural arteriovenous fistulas (DAVFs) are rare and
      aggressive lesions, usually treated by microsurgical disconnection of the
      fistula. Transarterial embolization rarely is performed because of the risk of
      retinal ischemia. Transvenous embolization has been reported as an alternative
      approach. We describe our experience in transvenous embolization of ethmoidal
      DAVFs and review the literature focusing on technical and safety aspects of the
      procedure. METHODS: We retrospectively identified 4 patients with ethmoidal DAVFs
      treated by transvenous embolization in a single center. Clinical data and
      angiographic images were reviewed. We reviewed the literature after PubMed
      searching for articles describing patients treated by a transvenous approach.
      RESULTS: One patient was treated by transvenous coiling and 3 patients by
      retrograde Onyx injection through a detachable-tip microcatheter. Three fistulas
      drained in an ascending cortical frontal vein and one drained posteriorly in the
      olfactory vein. In all patients the fistula was occluded, in one case an
      asymptomatic hemorrhage occurred. In the literature 12 further cases of
      transvenous embolization of ethmoidal DAVFs have been reported. CONCLUSIONS:
      Transvenous embolization is an effective approach for the treatment of ethmoidal
      DAVFs in properly selected patients. Onyx injection through detachable-tip
      microcatheters increases the feasibility of the intervention.

PMID- 29180086
TI  - History, Current Situation, and Future Development of Endoscopic Neurosurgery in
      China.
AB  - OBJECTIVE: During the past few decades, Chinese endoscopic neurosurgery has
      rapidly developed in synchrony with the rest of the world. The aim of this
      article is to review the development of Chinese endoscopic neurosurgery,
      including its birth, growth, current situation, and prospects. METHODS: The
      history of Chinese endoscopic neurosurgery development can be divided into 3
      stages: cognition and initial stage (1964-1995), exploration and maturity stage
      (1995-2006), and rapid development and promotion stage (2006-present). RESULTS:
      In the first stage, we mainly began to become aware of endoscopic neurosurgery
      from the translation and review of literature. In the mid to late 1990s, Chinese
      neurosurgery pioneers began using neuroendoscopic techniques. In the following
      decade, many leading neurosurgeons made persistent efforts to push the
      development of Chinese endoscopic neurosurgery forward, focusing on advocating
      for and promoting and popularizing neuroendoscopic technology. In the rapid
      development and promotion stage, many representative national and regional
      neurosurgical centers became skilled and efficient in the application of
      neuroendoscopic technology and became new advocates of the technology. The number
      of cases, level of technology, and treatment effectiveness are gradually nearing
      international standards. However, future development requires promotion of
      balanced development to decrease regional disparities, further strengthen
      international exchanges, follow the latest developments, and constantly innovate
      for continuous improvement. CONCLUSIONS: Following the dramatic efforts of
      several pioneers, development of Chinese endoscopic neurosurgery has been
      considerable, and it has become an important component of neurosurgery worldwide.

PMID- 29180087
TI  - Changes in Blood Flow Velocity of the Middle Cerebral Artery After Carotid
      Endarterectomy: Daily Assessment with Transcranial Color-Coded Sonography.
AB  - BACKGROUND: Hyperperfusion syndrome (HPS) is a well-known complication of carotid
      endarterectomy (CEA) warranting repeatable inexpensive monitoring. Transcranial
      color-coded sonography (TCCS) may provide a potential modality for such
      monitoring, but little is known about TCCS trends after CEA. METHODS: Between
      January 2016 and February 2017, we prospectively included patients with CEA at
      our institute in this study. TCCS was performed preoperatively and repeated daily
      from the operation day until postoperative day (POD) 7. Daily trends in mean flow
      velocity (MFV) at the M1 portion of the middle cerebral artery were compared
      between patients with and without HPS. RESULTS: Among 35 patients with CEA, daily
      TCCS monitoring was performed in 18 patients (mean age +/- SD, 72 +/- 7 years;
      male/female, 17:1). Among these 18 patients, 3 had probable HPS. On POD 0, MFV of
      the 18 patients showed a 32% increase from the initial preoperative value (from
      52.5 to 69.4 cm/s, P = 0.0013). This increased MFV lasted for several days and
      recovered gradually by POD 7. Patients with probable HPS demonstrated a trend to
      higher MFV than those without; however, the difference was below the significance
      level. CONCLUSIONS: We used daily TCCS after CEA to depict cerebral blood flow
      changes after CEA in our cohort. This technique may be useful both for the
      detection and prevention of HPS.

PMID- 29180088
TI  - Simple New Screw Insertion Technique without Extraction for Broken Pedicle
      Screws.
AB  - OBJECTIVE: Spinal transpedicular screw fixation is widely performed. Broken
      pedicle screw rates range from 3%-7.1%. Several techniques have been described
      for extraction of broken pedicle screws. However, most of these techniques
      require special instruments. We describe a simple, modified technique for
      management of broken pedicle screws without extraction. No special instruments or
      drilling in an adjacent pedicle are required. METHODS: We used a high-speed air
      drill with a round burr. With C-arm fluoroscopy guidance, the distal fragment of
      a broken pedicle screw was palpated using free-hand technique through the screw
      entry hole. A high-speed air drill with a round burr (not a diamond burr) was
      inserted through the hole. Drilling began slowly and continued until enough space
      was obtained for new screw insertion. Using this space, we performed new pedicle
      screw fixation medially alongside the distal fragment of the broken pedicle
      screw. We performed the insertion with a previously used entry hole and pathway
      in the pedicle. The same size pedicle screw was used. RESULTS: Three patients
      were treated with this modified technique. New screw insertion was successful in
      all cases after partial drilling of the distal broken pedicle screw fragment.
      There were no complications, such as screw loosening, dural tears, or root
      injury. CONCLUSION: We describe a simple, modified technique for management of
      broken pedicle screws without extraction. This technique is recommended in
      patients who require insertion of a new screw.

PMID- 29180089
TI  - The pCONus2 Neck-Bridging Device: Early Clinical Experience and Immediate
      Angiographic Results.
AB  - BACKGROUND: Treating wide-necked aneurysms is challenging for the interventional
      neuroradiologist. Recently, numerous devices dedicated to the treatment of these
      aneurysms have become available. We report our early experience using the pCONus2
      device and present the technical success rate, clinical outcomes, and immediate
      angiographic occlusion rates. METHODS: We performed a retrospective review of
      prospectively collected data to identify patients treated with the pCONus2 device
      between February 2015 and February 2017. RESULTS: We identified 12 patients (10
      females) treated with the pCONus2 device. The average patient age was 56.6 +/-
      15.8 years (range, 13-71 years). The average aneurysm dome width was 8.83 +/- 5.3
      mm (range, 3.8-20 mm), the average dome height was 7.23 +/- 4.06 mm (range, 3.36
      15 mm), and the average neck width was 5.88 +/- 2.92 mm (range, 2.77-11 mm). The
      angulation of the aneurysm to the parent vessel varied between 0 and 78 degrees 
      (mean, 32.2 degrees ). Ten aneurysms were located in the anterior circulation,
      and 2 were in the posterior circulation. Immediate posttreatment angiography
      showed 11 aneurysms with modified Raymond-Roy classification (mRRC) grade I
      occlusion and 1 aneurysm with mRRC grade II occlusion. There were no deaths or
      hemorrhagic complications. Three patients developed small thrombi during
      treatment, all of whom were successfully treated with glycoprotein IIb/IIIa
      antagonists. Early angiographic follow-up data for 6 patients showed adequate
      aneurysm occlusion in 5 patients and aneurysm recanalization in 1 patient.
      CONCLUSIONS: The early results on the use of the pCONus2 device suggest that it
      can be useful for treating wide-necked aneurysms; however, larger studies with
      longer-term follow-up data are needed.

PMID- 29180090
TI  - Neurologic Deterioration in Patients with Moyamoya Disease during Pregnancy,
      Delivery, and Puerperium.
AB  - BACKGROUND: We reviewed our clinical experience of patients with moyamoya disease
      (MMD) who gave birth and assessed characteristics of those experiencing
      neurologic deterioration. METHODS: The patients were classified into patients
      diagnosed with MMD during pregnancy and puerperium (group 1) and those diagnosed
      before pregnancy (group 2). We retrospectively reviewed patient characteristics,
      MMD treatment, neurologic symptoms before and during pregnancy and/after
      puerperium, obstetrical history, and delivery type in groups 1 and 2. RESULTS:
      Group 1 included 2 patients with deterioration of pre-existing transient ischemic
      attacks (TIAs) and acute cerebral infarction and 1 patient with seizures and
      newly developed TIAs during pregnancy and/or puerperium. Group 2 included 20
      patients with 23 pregnancies. In group 2, 4 patients had deterioration of TIAs
      during pregnancy and puerperium. There were significant differences between the
      cases without neurologic deterioration and with deterioration in group 2 (TIAs
      >=10 before pregnancy, 0% vs. 75%, P = 0.002; severely reduced regional
      cerebrovascular reserve on single-photon emission computed tomography, 10.5% vs.
      100%, P = 0.002; and surgical revascularization before pregnancy, 75% vs. 15.8%,
      P = 0.04). In groups 1 and 2, 6 of the 7 cases in which TIAs occurred or worsened
      during pregnancy or puerperium recovered to prepregnancy TIA levels after
      puerperium. CONCLUSIONS: Patients with severely reduced regional cerebrovascular
      reserve on single-photon emission computed tomography and frequent TIAs before
      pregnancy may experience neurologic deterioration during pregnancy, delivery, and
      puerperium. Surgical revascularization before pregnancy may decrease neurologic
      deterioration during these periods.

PMID- 29180091
TI  - Prevalence of Surgically Untreated Face, Head, and Neck Conditions in Uganda: A
      Cross-Sectional Nationwide Household Survey.
AB  - BACKGROUND: The Surgeons OverSeas Assessment of Surgical Need tool (SOSAS) was
      created to evaluate the burden of surgically treatable conditions in low- and
      middle-income countries. The goal of our study is to describe the face, head, and
      neck (FHN) conditions that need surgical care in Uganda, along with barriers to
      that care and disability from these conditions. METHODS: A 2-stage cluster
      randomized SOSAS survey was administered in a cross-sectional manner between
      August and September 2014. Participants included randomly selected persons in 105
      enumeration areas in 74 districts throughout Uganda with 24 households in each
      cluster. The SOSAS survey collected demographic and clinical data on all
      respondents. Univariate and multivariate logistic models evaluated associations
      of demographic characteristics and clinical characteristics of the FHN conditions
      and outcomes of whether health care was sought or surgical care was received.
      RESULTS: Of the 4428 respondents, 331 (7.8%) reported having FHN conditions. The
      most common types of conditions were injury-related wounds. Of those who reported
      an FHN condition, 36% reported receiving no surgical care whereas 82.5% reported
      seeking health care. In the multivariate model, literacy and type of condition
      were significant predictors of seeking health care whereas village type,
      literacy, and type of condition remained significant predictors of receiving
      surgical care. CONCLUSIONS: Many individuals in Uganda are not receiving surgical
      care and barriers include costs, rural residency, and literacy. Our study
      highlights the need for targeted interventions in various parts of Uganda to
      increase human resources for surgery and expand surgical capacity.

PMID- 29180092
TI  - Future considerations for clinical dermatology in the setting of 21st century
      American policy reform: The Relative Value Scale Update Committee.
AB  - The American Medical Association-Specialty Society Relative Value Scale Update
      Committee, also known as the RUC, plays a critical role in assessing the relative
      value of physician services and procedures. This committee provides access for
      all physicians, including dermatologists, to the reimbursement process. Since the
      introduction of the Resource-Based Relative Value Scale by Medicare, the RUC has
      done important work to evaluate and refine reimbursement for physician services.
      The RUC recommendations have also led the Current Procedural Terminology (CPT)
      Editorial Panel to develop additional reimbursement codes as new procedures and
      services are developed. In this article (from the series Future Considerations
      for Clinical Dermatology in the Setting of 21st Century American Policy Reform),
      we will review the RUC, including its history and membership, the RUC update
      process, and a brief discussion of a few issues of particular importance to
      dermatologists.

PMID- 29180093
TI  - Estimating the cost of skin cancer detection by dermatology providers in a large
      health care system.
AB  - BACKGROUND: Data on the cost and efficiency of skin cancer detection through
      total body skin examination are scarce. OBJECTIVE: To determine the number needed
      to screen (NNS) and biopsy (NNB) and cost per skin cancer diagnosed in a large
      dermatology practice in patients undergoing total body skin examination. METHODS:
      This is a retrospective observational study. RESULTS: During 2011-2015, a total
      of 20,270 patients underwent 33,647 visits for total body skin examination; 9956
      lesion biopsies were performed yielding 2763 skin cancers, including 155
      melanomas. The NNS to detect 1 skin cancer was 12.2 (95% confidence interval [CI]
      11.7-12.6) and 1 melanoma was 215 (95% CI 185-252). The NNB to detect 1 skin
      cancer was 3.0 (95% CI 2.9-3.1) and 1 melanoma was 27.8 (95% CI 23.3-33.3). In a
      multivariable model for NNS, age and personal history of melanoma were
      significant factors. Age switched from a protective factor to a risk factor at 51
      years of age. The estimated cost per melanoma detected was $32,594 (95% CI
      $27,326-$37,475). LIMITATIONS: Data are from a single health care system and
      based on physician coding. CONCLUSION: Melanoma detection through total body skin
      examination is most efficient in patients >=50 years of age and those with a
      personal history of melanoma. Our findings will be helpful in modeling the cost
      effectiveness of melanoma screening by dermatologists.

PMID- 29180094
TI  - Validation study of the Vitiligo Extent Score-plus.

PMID- 29180095
TI  - Drug survival of secukinumab in real-world plaque psoriasis patients: A 52-week,
      multicenter, retrospective study.

PMID- 29180097
TI  - Lack of correlation of the patient-derived Vitiligo Disease Activity Index with
      the clinician-derived Vitiligo Area Scoring Index.

PMID- 29180098
TI  - Spontaneous painful disease in companion animals can facilitate the development
      of chronic pain therapies for humans.
AB  - OBJECTIVE: To outline the role that spontaneous osteoarthritis (OA) in companion
      animals can play in translational research and therapeutic pharmacological
      development. OUTLINE: Narrative review summarizing the opportunities and
      limitations of naturally occurring, spontaneous OA as models of human OA pain,
      with a focus on companion animal pets. The background leading to considering
      inserting spontaneous disease models in the translational paradigm is provided.
      The utility of this model is discussed in terms of outcome measures that have
      been validated as being related to pain, and in terms of the potential for target
      discovery is outlined. The limitations to using companion animal pets as models
      of human disease are discussed. CONCLUSIONS: Although many steps along the
      translational drug development pathway have been identified as needing
      improvement, spontaneous painful OA in companion animals offers translational
      potential. Such 'models' may better reflect the complex genetic, environmental,
      temporal and physiological influences present in humans and current data suggests
      the predictive validity of the models are good. The opportunity for target
      discovery exists but is, as yet, unproven.

PMID- 29180096
TI  - Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary
      skin tumor from other metastatic neuroendocrine carcinomas: The ELECTHIP
      criteria.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) can present as a cutaneous tumor or a
      lymph node metastasis without a primary tumor. MCC presenting without a primary
      tumor (MCCWOPT) can be misinterpreted on histologic examination as lymph node
      metastasis (LNM) from another neuroendocrine carcinoma (LNMNEC). However, this
      distinction is crucial for therapeutic management. OBJECTIVE: To determine the
      discriminative criteria for the differential diagnosis of MCCWOPT, LNM from
      cutaneous MCC, and LNMNECs. METHODS: Clinical, morphologic, and
      immunohistochemical data (expression of cytokeratins AE1, AE3, 7, 19, and 20;
      chromogranin A, synaptophysin, thyroid transcription factor-1 [TTF-1]), as well
      as the presence of Merkel cell polyomavirus (by immunohistochemistry and PCR)
      were compared in patients with MCCWOPT (n = 17), LNM from a cutaneous MCC (n =
      11), and LNMNEC (n = 20; 8 lung, 7 thyroid, 3 digestive tract, 2 other). RESULTS:
      MCC (including MCCWOPT and LNM from a cutaneous MCC) differed from LNMNEC by 7
      discriminative criteria: 1) elderly age, 2) location of the tumor, 3) extent of
      the disease, 4) cytokeratin expression, 5) TTF-1 expression, 6) histologic type,
      and 7) Merkel cell polyomavirus detection, summarized under the acronym ELECTHIP.
      All MCC patients had >=5 of the ELECTHIP criteria, whereas all patients with
      LNMNEC (except 1) had <3 criteria. LIMITATIONS: The discriminant ability of the
      ELECTHIP criteria should be validated in a second independent set. CONCLUSION:
      MCCWOPT can be distinguished from other LNMNEC by the ELECTHIP criteria.

PMID- 29180099
TI  - Comparison of fat suppression capability for chest MR imaging with Dixon, SPAIR
      and STIR techniques at 3 Tesla MR system.
AB  - PURPOSE: To directly compare fat suppression efficacy of Dixon, spectral
      attenuated inversion recovery (SPAIR) and short tau inversion recovery (STIR)
      techniques for a 3T MR system. MATERIALS AND METHODS: Nineteen consecutive
      patients (11 men, 8 women; mean age 67.9years) underwent chest MR imaging.
      Contrast-noise ratio (CNR) between muscle and fat (CNRFat) was calculated by ROI
      measurement. Then, two radiologists used a five-point scale for visual assessment
      of image quality, fat suppression capability and lesion detection. Next, the
      quantitative calculations obtained with all three techniques were compared by
      means of Tukey's honest significant difference (HSD) test. Inter-observer
      agreements were assessed by kappa statistics and chi2 test. Fisher's least
      significant difference (LSD) test was used for comparison among all scores.
      RESULTS: CNRFat of SPAIR were significantly higher than those of Dixon and STIR
      (p<0.001). Inter-observer agreements were assessed as significantly moderate,
      substantial or almost perfect (0.51<kappa<0.89, p<0.0001). Total image quality
      and fat suppression capability of Dixon and STIR were significantly higher than
      those of SPAIR (p<0.001). CONCLUSION: Dixon technique has better fat suppression
      capability on T2-weighted turbo SE imaging than SPAIR technique on chest MR
      imaging examined with a 3T MR system, although it can't substitute STIR technique
      on fat suppression and lesion visualization.

PMID- 29180100
TI  - Fully automated contour detection of the ascending aorta in cardiac 2D phase
      contrast MRI.
AB  - PURPOSE: In this study we proposed a fully automated method for localizing and
      segmenting the ascending aortic lumen with phase-contrast magnetic resonance
      imaging (PC-MRI). MATERIAL AND METHODS: Twenty-five phase-contrast series were
      randomly selected out of a large population dataset of patients whose cardiac MRI
      examination, performed from September 2008 to October 2013, was unremarkable. The
      local Ethical Committee approved this retrospective study. The ascending aorta
      was automatically identified on each phase of the cardiac cycle using a priori
      knowledge of aortic geometry. The frame that maximized the area, eccentricity,
      and solidity parameters was chosen for unsupervised initialization. Aortic
      segmentation was performed on each frame using active contouring without edges
      techniques. The entire algorithm was developed using Matlab R2016b. To validate
      the proposed method, the manual segmentation performed by a highly experienced
      operator was used. Dice similarity coefficient, Bland-Altman analysis, and
      Pearson's correlation coefficient were used as performance metrics. RESULTS:
      Comparing automated and manual segmentation of the aortic lumen on 714 images,
      Bland-Altman analysis showed a bias of -6.68mm2, a coefficient of repeatability
      of 91.22mm2, a mean area measurement of 581.40mm2, and a reproducibility of 85%.
      Automated and manual segmentation were highly correlated (R=0.98). The Dice
      similarity coefficient versus the manual reference standard was 94.6+/-2.1%
      (mean+/-standard deviation). CONCLUSION: A fully automated and robust method for
      identification and segmentation of ascending aorta on PC-MRI was developed. Its
      application on patients with a variety of pathologic conditions is advisable.

PMID- 29180101
TI  - Beyond war and PTSD: The crucial role of transition stress in the lives of
      military veterans.
AB  - Although only a relatively small minority of military veterans develop
      Posttraumatic Stress Disorder (PTSD), mental health theory and research with
      military veterans has focused primarily on PTSD and its treatment. By contrast,
      many and by some accounts most veterans experience high levels of stress during
      the transition to civilian life, however transition stress has received scant
      attention. In this paper we attempt to address this deficit by reviewing the
      wider range of challenges, rewards, successes, and failures that transitioning
      veterans might experience, as well as the factors that might moderate these
      experiences. To illuminate this argument, we briefly consider what it means to
      become a soldier (i.e., what is required to transition into military service) and
      more crucially what kind of stressors veterans might experience when they attempt
      to shed that identity (i.e., what is required to transition out of military
      service). We end by suggesting how an expanded research program on veteran
      transition stress might move forward.

PMID- 29180102
TI  - Insomnia in United States military veterans: An integrated theoretical model.
AB  - Marked by difficulty falling or staying asleep and/or poor sleep leading to
      daytime dysfunction, insomnia contributes to functional impairment, poor health,
      and increased healthcare utilization when left untreated. As many as two-thirds
      of Iraq and Afghanistan military veterans complain of insomnia. Older veterans of
      prior conflicts report insomnia occurring since initial service, suggesting a
      chronic nature to insomnia in this population. Despite insomnia's high prevalence
      and severe consequences, there is no theoretical model to explain either the
      onset or chronicity of insomnia in this growing patient population. Existing
      theories view insomnia as an acute, unidirectional phenomenon and do little to
      elucidate long-term consequences of such problems. Existing theories also fail to
      address mechanisms by which acute insomnia becomes chronic. This paper presents
      an original, integrated theoretical model that draws upon constructs from several
      prominent behavioral medicine theories to reconceptualize insomnia as a chronic,
      cyclical problem that is both a consequence and predictor of stress. Additional
      research examining the relationships between stress, sleep, resilience, and
      outcomes of interest could inform clinical and research practices. Addressing
      sleep problems early could potentially enhance adaptive capacity, thereby
      reducing the risk for subsequent negative outcomes.

PMID- 29180103
TI  - A molecular phylogeny of the bladed Bangiales (Rhodophyta) in China provides
      insights into biodiversity and biogeography of the genus Pyropia.
AB  - A molecular taxonomic study was undertaken for the first time of the bladed
      Bangiales of the mainland coast of China (Northwest Pacific) based on sequence
      data of 201 plastid rbcL and 148 nuclear 18S sequences of historical and
      contemporary specimens. The results revealed that only one genus of bladed
      Bangiales, Pyropia, was present along Chinese coast. Species delimitation was
      determined using two empirical methods: the Automatic Barcode Gap Discovery
      (ABGD) and General Mixed Yule Coalescence (GMYC) coupled with detection of
      monophyly in tree reconstruction. At least fourteen species of Pyropia were
      recovered. Six species were confirmed that had been recorded previously based on
      morphology (Py. suborbiculata, Py. yezoensis, Py. haitanensis, Py. katadae, Py.
      tenera and Py. acanthophora), three species were recorded from China for the
      first time (Py. kinositae, Py. pseudolinearis and Py. tanegashimensis), and five
      cryptic species that did not match any molecular sequences were also discovered.
      The phylogeny of the concatenated rbcL and 18S dataset resolved three singletons
      and four clades. Each clades has a strong trend towards occupying a biogeographic
      region, but they are not confined to them. A transoceanic and antitropical
      pattern of distribution was found for Pyropia at both the subgeneric and species
      level. This together with high biodiversity (ca. 30% of all known Pyropia
      species) indicates that the Northwest Pacific might act as a centre of origin for
      modern distribution of Pyropia since the early Cenozoic.

PMID- 29180104
TI  - The Nkd EF-hand domain modulates divergent wnt signaling outputs in zebrafish.
AB  - Wnt proteins regulate diverse biological responses by initiating two general
      outcomes: beta-catenin-dependent transcription and beta-catenin-independent
      activation of signaling cascades, the latter including modulation of calcium and
      regulation of cytoskeletal dynamics (Planar Cell Polarity, PCP). It has been
      difficult to elucidate the mechanisms by which Wnt signals are directed to effect
      one or the other outcome due to shared signaling proteins between the beta
      catenin-dependent and -independent pathways, such as the Dishevelled binding
      protein Naked. While all Naked paralogs contain a putative calcium-binding
      domain, the EF-Hand, Drosophila Naked does not bind calcium. Here we find a
      lineage-specific evolutionary change within the Drosophila Naked EF-hand that is
      not shared with other insects or vertebrates. We demonstrate the necessary role
      of the EF-hand for Nkd localization changes in calcium fluxing cells and using in
      vivo assays, we identify a role for the zebrafish Naked EF-hand in PCP but not in
      beta-catenin antagonism. In contrast, Drosophila-like Nkd does not function in
      PCP, but is a robust antagonist of Wnt/beta-catenin signaling. This work reveals
      that the zebrafish Nkd1 EF-hand is essential to balance Wnt signaling inputs and
      modulate the appropriate outputs, while the Drosophila-like EF-Hand primarily
      functions in beta-catenin signaling.

PMID- 29180105
TI  - Sex hormone-binding globulin b expression in the rainbow trout ovary prior to sex
      differentiation.
AB  - Salmonids have two sex hormone-binding globulin (Shbg) paralogs. Shbga is mainly
      expressed in the liver, while Shbgb is secreted by the granulosa cells of the
      rainbow trout ovary. Coexpression of shbgb and the gonadal aromatase cyp19a1a
      mRNAs been observed in granulosa cells, suggesting a physiological coordination
      between Shbgb expression and estrogen synthesis. As estrogens are essential for
      female sex determination in the fish ovary, we propose that Shbgb participates in
      early ovarian differentiation, either by binding with estrogen or through another
      mechanism that remains to be discovered. To elucidate this potential role,
      monosex populations of female trout were studied during the molecular ovarian
      differentiation period (28-56 dpf). shbgb mRNA expression was measured using qPCR
      and compared with expression of genes for other ovarian markers (cyp19a1a, foxl2,
      follistatin, and estrogen receptors). shbgb transcript expression was detected
      during the final stages of embryonic development (21-26 dpf) and during molecular
      ovarian differentiation (32-52 dpf) after hatching (which occurred at 31 dpf). In
      situ hybridization localized shbgb transcription to the undifferentiated ovary at
      42 dpf, and shbgb and cyp19a1a mRNA showed similar expression patterns. These
      results suggest that Shbgb is involved in early ovarian differentiation,
      supporting an important role for the salmonid shbgb gene in sex determination.

PMID- 29180106
TI  - The influence of endogenous attention on contrast perception, contrast
      discrimination, and saccadic reaction time.
AB  - Visual spatial attention has been shown to influence both contrast detection and
      suprathreshold contrast perception, as well as manual and saccadic reaction times
      (SRTs). Because SRTs are influenced also by stimulus contrast, we investigated if
      the enhancement of perceived contrast that accompanies attention could account
      for the shorter SRTs observed for attended targets locations. We conducted two
      dual-task experiments to assess psychophysical and oculomotor responses to non
      foveal targets of various contrast for different spatial-attention-cueing
      conditions. Cues were either: valid, an arrow at fixation pointing in the
      direction of the upcoming target; invalid, an arrow pointing in a different
      direction from the target; or neutral, a small circle instead of an arrow. In
      both experiments, subjects were instructed to make a saccade to the location of a
      subsequent, briefly flashed target. In the first experiment, the psychophysical
      judgment was a two-alternative-forced-choice (2AFC) contrast-detection task, in
      which subjects reported whether the flashed target was at a near (3 degrees ) or
      far (6 degrees ) eccentricity. In the second experiment, the judgment was a
      contrast matching task, in which subjects reported whether the target's contrast
      was higher or lower than a remembered standard contrast. The results exhibit a
      robust, ~40-50 ms reduction of SRTs with a valid compared to an invalid cue.
      Cueing effects on contrast detection and matching were small and inconsistent
      across subjects. Hence, the observed decrease in SRTs could not be accounted for
      fully by an enhancement in the target's effective contrast due to attention, as
      attended and unattended targets that were equally detectable or were perceived to
      have the same suprathreshold contrast showed substantial differences in SRT.

PMID- 29180107
TI  - Limited transfer of visual skill in orientation discrimination to locations
      treated by pre-testing and subliminal exposure.
AB  - Substantial transfer of perceptual skill learning can be achieved across large
      distances in the visual field by a brief pre-test, training-plus-exposure, or a
      double-training paradigm (Xiao et al., 2008; Zhang, Xiao, et al., 2010; Zhang,
      Zhang, et al., 2010). Additionally, subliminal exposure has been shown to be
      beneficial for subsequent perceptual learning. Here, we tested the generalization
      of orientation discrimination learning from a fully trained location towards four
      other test locations, either in the same or opposite hemifield as the training
      location, which each were subjected to a different type of pre-conditioning. In
      one test location, there was brief pre-testing in the first session. Two other
      locations were stimulated by masked stimuli similar or identical to concurrently
      presented stimuli in the training location. In the fourth test location, no
      stimuli were presented during training. Generalization of training to test
      locations was measured in the session immediately following the completion of
      training in the training location. Moreover, to test the robustness of transfer,
      training was continued in all four test locations. The experiment as a whole
      consisted of 15 sessions of orientation discrimination learning at the training
      location, followed by 15 sessions of training in the test locations. We found
      only limited generalization from the trained to the test locations. Performance
      in pre-tested and stimulated test locations showed a small advantage compared to
      the unstimulated test location. However, this advantage disappeared within a few
      sessions of further training in the test locations.

PMID- 29180108
TI  - Palmitate induces neuroinflammation, ER stress, and Pomc mRNA expression in
      hypothalamic mHypoA-POMC/GFP neurons through novel mechanisms that are prevented
      by oleate.
AB  - Dietary fats can modulate brain function. How free fatty acids (FFAs) alter
      hypothalamic pro-opiomelanocortin (POMC) neurons remain undefined. The saturated
      FFA, palmitate, increased neuroinflammatory and ER stress markers, as well as
      Pomc mRNA levels, but did not affect insulin signaling, in mHypoA-POMC/GFP-2
      neurons. This effect was mediated through the MAP kinases JNK and ERK. Further,
      the increase in Pomc was dependent on palmitoyl-coA synthesis, but not de novo
      ceramide synthesis, as inhibition of SPT enhanced palmitate-induced Pomc
      expression, while methylpalmitate had no effect. While palmitate concomitantly
      induces neuroinflammation and ER stress, these effects were independent of
      changes in Pomc expression. Palmitate thus has direct acute effects on Pomc,
      which appears to be important for negative feedback, but not directly related to
      neuroinflammation. The monounsaturated FFA oleate completely blocked the
      palmitate-mediated increase in neuroinflammation, ER stress, and Pomc mRNAs. This
      study provides insight into the complex central metabolic regulation by FFAs.

PMID- 29180109
TI  - Relaxin induces up-regulation of ADAM10 metalloprotease in RXFP1-expressing cells
      by PI3K/AKT signaling.
AB  - ADAM10 metalloprotease is required for activation of Notch-1, a transmembrane
      receptor regulating cell differentiation, proliferation and apoptosis, whose
      intracellular proteolytic fragment NICD mediates some key cardiovascular effects
      of the hormone relaxin (RLX). This study demonstrates the involvement of ADAM10
      and PI3K/Akt signaling in mediating RLX-induced Notch-1 activation. H9c2
      cardiomyocytes and NIH3T3 fibroblasts were incubated with human RLX-2 (17 nmol/l,
      24 h) in presence or absence of the PI3K or Akt inhibitors wortmannin (WT, 100
      nmol/l) and triciribine (TCN, 1 MUmol/l). Cyclohexanedione-inactivated RLX (iRLX)
      served as negative control. RLX significantly increased Akt phosphorylation,
      ADAM10 and NICD expression, which were abolished by WT or TCN and did not occur
      with iRLX. These findings highlight a new receptor-specific signal transduction
      pathway of RLX.

PMID- 29180110
TI  - Interleukin 6 inhibits the differentiation of rat stem Leydig cells.
AB  - Inflammation causes male hypogonadism. Several inflammatory cytokines, including
      interleukin 6 (IL-6), are released into the blood and may suppress Leydig cell
      development. The objective of the present study was to investigate whether IL-6
      affected the proliferation and differentiation of rat stem Leydig cells. Leydig
      cell-depleted rat testis (in vivo) and seminiferous tubules (in vitro) with
      ethane dimethane sulfonate (EDS) were used to explore the effects of IL-6 on stem
      Leydig cell development. Intratesticular injection of IL-6 (10 and 100 ng/testis)
      from post-EDS day 14 to 28 blocked the regeneration of Leydig cells, as shown by
      the lower serum testosterone levels (21.6% of the control at 100 ng/testis dose),
      the down-regulated Leydig cell gene (Lhcgr, Star, Cyp11a1, Cyp17a1, and Hsd17b3)
      expressions, and the reduced Leydig cell number. Stem Leydig cells on the surface
      of the seminiferous tubules were induced to enter the Leydig cell lineage in
      vitro in the medium containing luteinizing hormone and lithium. IL-6 (1, 10, and
      100 ng/ml) concentration-dependently decreased testosterone production and Lhcgr,
      Cyp11a1, Cyp17a1, Hsd17b3 and Insl3 mRNA levels. The IL-6 mediated effects were
      antagonized by Janus kinase 1 (JAK) inhibitor (filgotinib) and Signal Transducers
      and Activators of Transcription 3 (STAT3) inhibitor (S3I-201), indicating that a
      JAK-STAT3 signaling pathway is involved. In conclusion, our results demonstrated
      that IL-6 was an inhibitory factor of stem Leydig cell development.

PMID- 29180111
TI  - Tactile acuity is reduced in people with chronic neck pain.
AB  - BACKGROUND: Tactile acuity deficits have been demonstrated in a range of
      persistent pain conditions and may reflect underlying cortical re-organisation.
      OBJECTIVE: This study aimed to determine whether tactile acuity is impaired in
      people with chronic neck pain relative to controls, and whether deficits relate
      to pain location, duration and intensity. METHODS: In this cross-sectional study,
      20 people with chronic neck pain (5 idiopathic neck pain; 15 whiplash-associated
      disorder) and 20 pain-free controls underwent two-point discrimination (TPD)
      testing at the neck, back and arm, and point-to-point (PTP) and graphesthesia
      tests of tactile acuity at the neck and arm. RESULTS: Linear mixed effects models
      demonstrated a significant group*body region interaction for TPD, Graphesthesia
      and PTP tests (Ps < 0.001), with post hoc tests showing impaired TPD in people
      with neck pain relative to controls at the neck, low back, and arm (P <= 0.001).
      Graphesthesia and PTP was also impaired at the neck (P < 0.001) but not the arm
      (P >= 0.48). TPD correlated with intensity and duration of pain (Pearson's r =
      0.48, P < 0.05; Pearson's r = 0.77, P < 0.01). There was no sig difference
      between the two neck pain groups for any tactile acuity measure (TPD: P = 0.054;
      Graphesthesia; P = 0.67; Point to Point: P = 0.77), however, low power limited
      confidence in this comparison. CONCLUSION: People with chronic neck pain
      demonstrated tactile acuity deficits in painful and non-painful regions when
      measured using the TPD test, with the magnitude of deficits appearing greatest at
      the neck. The study also revealed a positive relationship between TPD and pain
      intensity/duration, further supporting the main study finding.

PMID- 29180112
TI  - MRI evaluation of the effects of extension exercises on the disc fluid content
      and location of the centroid of the fluid distribution.
AB  - BACKGROUND: McKenzie prone press-up exercises have been hypothesised to reduce
      intradiscal pressure, allowing fluid to be reabsorbed into the disc, which could
      improve the internal stability and local chemical milieu of the disc, potentially
      reducing symptoms. OBJECTIVE: To investigate the immediate effects of prone press
      up exercises on lumbar disc fluid content and movement. DESIGN: Quantification of
      MRI changes before and after a single exercise session. METHODS: The mid-sagittal
      T2-weighted MR images of 22 volunteers with low back pain were obtained before
      and immediately after performing press-up exercises. The whole disc and nucleus
      regions of the L4-5 and L5-S1 discs were then segmented, and their mean signal
      intensity (MSI) and signal intensity weighted centroid (SIWC) were computed to
      estimate disc fluid content and displacement. RESULTS: There were no significant
      differences between the MSI and the vertical position of the SIWC of the whole
      disc before and after extension at either disc level (effect size [ES]: -0.23 to
      0.09). There was a significant anterior displacement (0.1 +/- 5.4 mm) of the
      location of the SIWC of the disc after extension exercise at L4-5 (ES: 0.22), but
      not at L5-S1 (ES: 0.00) or at either level for the nucleus region (ES: -0.06;
      0.16). CONCLUSION: Little evidence was found supporting the hypothesis that press
      up exercises affect disc fluid content and distribution. Novel parameters
      reflecting fluid distribution detected similar or larger effects of the extension
      than MSI. If such exercises are effective in reducing symptoms, it is likely
      through other mechanisms than by changing fluid content or distribution.

PMID- 29180113
TI  - Two common mild analgesics have no effect on general endocrine mediated endpoints
      in zebrafish (Danio rerio).
AB  - Mild analgesics such as acetylsalicylic acid (ASA) and acetaminophen (APAP) exert
      their pain-relieving effect in humans by inhibition of prostaglandin synthesis.
      Prostaglandins play key roles in developmental and reproductive processes in
      vertebrates, and in recent years, it has been suggested that weak analgesics
      might also act as endocrine disrupters. In a set of experiments we investigated
      if ASA and APAP affect well-established endocrine endpoints in zebrafish (Danio
      rerio), which is a commonly used model organism in the investigation of endocrine
      disrupting chemicals. Zebrafish were exposed to APAP (0.22, 2.3, and 30mgL-1) or
      ASA (0.2, 0.5, 1.7, and 8.2mgL-1) from hatch to sexual maturity in a test design
      resembling the OECD Fish Sexual Development Test. No effects on sex ratio and
      vitellogenin levels were observed. Adult zebrafish were exposed to high
      concentrations (mgL-1) of ASA or APAP for eight or 14days. ASA reduced the levels
      of prostaglandin E2, but had no effect on the concentration of 11
      ketotestosterone and vitellogenin. Overall, ASA decrease prostaglandin E2
      concentrations, but well-established endpoints for endocrine disruption in
      zebrafish are generally not affected by aquatic exposure neither during
      development nor adulthood. According to the WHO/IPCS definition of an endocrine
      disrupter, the present results do not define APAP and ASA as endocrine
      disrupters.

PMID- 29180114
TI  - Novel and divergent viruses associated with Australian orchid-fungus symbioses.
AB  - Terrestrial orchids represent a symbiotic union between plants and mycorrhizal
      fungi. This study describes the occurrence and nature of viruses associated with
      one population of wild Pterostylis sanguinea orchids, including their fungal
      symbionts, over two consecutive years. A generic sequencing approach, which
      combined dsRNA-enrichment from plant and mycelial tissues, random amplification
      and high throughput shotgun sequencing was used to identify novel viruses. The
      majority of the virus-like sequences represent partial genomes, and their
      identification is based solely on de novo assembly of sequencing data. In orchid
      leaf tissues we found three isolates of a novel totivirus and an unclassified
      virus; both resemble fungus-infecting viruses. Two isolates of Ceratobasidium sp
      that were isolated from orchid underground stems contained at least 20 viruses,
      16 of which were previously described as alphapartitiviruses and
      betapartitiviruses. A novel hypovirus and a mitovirus were genetically distant
      from existing members of the genera and did not readily fit into recognised
      subgroups.

PMID- 29180115
TI  - Deletion of GIRK2 subunit containing GIRK channels of neurons expressing dopamine
      transporter decrease immobility time on forced swimming in mice.
AB  - We previously reported that non-narcotic antitussives possessing inhibitory
      actions on G protein-coupled inwardly rectifying potassium (GIRK) channels have
      antidepressant-like effects in the forced swimming test in normal and
      adrenocoticotropic hormone (ACTH) treated rats. Furthermore, the antidepressant
      like effects of the antitussives such as tipepidine were blocked by dopamine D1
      receptor antagonist, and inhibitory actions on GIRK channels of dopamine neurons
      may be involved in the antidepressant-like effects of tipepidine. In this study,
      we generated GIRK2DATKO mice with Girk2/Kcnj6 conditional deletion and assessed
      depression-related behavior of the mice. The Cre/loxP system was used to
      selectively delete GIRK2 subunit containing GIRK channels in the neurons
      expressing dopamine transporter. First, deletion of GIRK2 subunits in the ventral
      tegmental area (VTA) neurons expressing dopamine transporters was confirmed by
      hisitochemically and electrophysiologically. In the mice, a significant decrease
      in the immobility time of forced swimming test was observed. Locomotor activity
      of the mice was not changed compared to that of GIRK2floxed mice, when tested in
      the open field. These results suggest that the antidepressant-like effect of
      antitussives such as tipepidine may be caused partly through the inhibitory
      actions on GIRK channels in the dopamine neurons.

PMID- 29180116
TI  - Association of different neural processes during different emotional perceptions
      of white noise and pure tone auditory stimuli.
AB  - Sound is a sensory stimulant ubiquitously found throughout our environment.
      Humans have evolved a system that effectively and automatically converts sound
      sensory inputs into emotions. Although different emotional responses to sounds
      with different frequency characteristics are empirically recognized, there is a
      paucity of studies addressing different emotional responses to these sounds and
      the underlying neural mechanisms. In this study, we examined effects of pure tone
      (PT) and white noise (WN) inputs at ordinary loudness levels on emotional
      responses. We found that WN stimuli produced more aversive responses than PT
      stimuli. This difference was endorsed by larger late posterior positivity (LPP).
      In a source localization study, we found increased neural activity in the
      parietal lobe prior to LPP. These findings show that WN stimuli produce aversive
      perceptions compared with PT stimuli, at typical loudness levels. In addition,
      different emotional responses were processed in a similar manner as visual
      stimulations, as reflected by increased LPP activation. Various emotional effects
      of WN and PT stimuli, at ordinary loudness levels, could expand our understanding
      of adverse effects of noise as well as favorable effects associated with music.

PMID- 29180117
TI  - The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug
      resistance.
AB  - The FOXO3 and FOXM1 forkhead box transcription factors, functioning downstream of
      the essential PI3K-Akt, Ras-ERK and JNK/p38MAPK signalling cascades, are crucial
      for cell proliferation, differentiation, cell survival, senescence, DNA damage
      repair and cell cycle control. The development of resistance to both conventional
      and newly emerged molecularly targeted therapies is a major challenge confronting
      current cancer treatment in the clinic. Intriguingly, the mechanisms of
      resistance to 'classical' cytotoxic chemotherapeutics and to molecularly targeted
      therapies are invariably linked to deregulated signalling through the FOXO3 and
      FOXM1 transcription factors. This is owing to the involvement of FOXO3 and FOXM1
      in the regulation of genes linked to crucial drug action-related cellular
      processes, including stem cell renewal, DNA repair, cell survival, drug efflux,
      and deregulated mitosis. A better understanding of the mechanisms regulating the
      FOXO3-FOXM1 axis, as well as their downstream transcriptional targets and
      functions, may render these proteins reliable and early diagnostic/prognostic
      factors as well as crucial therapeutic targets for cancer treatment and
      importantly, for overcoming chemotherapeutic drug resistance.

PMID- 29180118
TI  - Role of bioactive lipofishins in prevention of inflammation and colon cancer.
AB  - Many clinical conditions exist in which it is desirable to stimulate or suppress
      the immune system, and many different drugs are able to do this. It is also well
      known that nutrition may affect human health and immune responses. Nutritional
      factors are crucial components of the diet and essential for normal growth and
      development of both vertebrate and invertebrate organisms. Many of these
      components have been shown to play different roles in the immune response and,
      under different circumstances, they can significantly modulate the immune system
      to create an effective response. Diet and its components are known to play an
      important factor in the process of inflammation and in turn on the health effects
      related to inflammation, such as cancer and cardiovascular diseases. Previous
      research so far has mainly looked at the effect of specific food stuffs or
      nutrients on inflammation and health outcomes. The aims of the present review was
      a) to underline the fact that diet as a whole plays an important role in
      modifying inflammation and health outcomes related to inflammation, aging, and
      colon cancer; b) to show the in vitro cytotoxic effect of LipoFishins (E
      Congerine 10423(r); AntiGanTM) obtained from the Atlantic Conger conger marine
      organism present on the Galician coast, against different human tumor cell lines;
      c) to show the in vivo effect of E-Congerine-10423(r) on colonic inflammation
      induced in mice by seven weeks' exposure to 2% of dextran sulfate sodium (DSS);
      and d) to show the effect of E-Congerine-10423(r) (AntiGanTM) on tumor markers
      (TMs) in healthy subjects and in patients with different types of cancer at the
      time of diagnosis. Preliminary data in a limited number of cases indicate that
      about 50% of the patients show a reduction in the levels of tumor markers (TM),
      and this response was much more evident in patients with cancer, when TM values
      are above normal range. Finally, all the above mentioned results suggest that
      diet has a major role in controlling inflammation and thereby plays an important
      role in the development or prevention of various chronic diseases, hence public
      health steps should be taken to modify the individual's whole diet and to promote
      the intake of specific natural compounds.

PMID- 29180119
TI  - Cyclopropane fatty acid synthesis affects cell shape and acid resistance in
      Leishmania mexicana.
AB  - Cyclopropane fatty acid synthase (CFAS) catalyzes the transfer of a methylene
      group from S-adenosyl methionine to an unsaturated fatty acid, generating a
      cyclopropane fatty acid (CFA). The gene encoding CFAS is present in many bacteria
      and several Leishmania spp. including Leishmania mexicana, Leishmania infantum
      and Leishmania braziliensis. In this study, we characterised the CFAS-null and 
      overexpression mutants in L. mexicana, the causative agent for cutaneous
      leishmaniasis in Mexico and central America. Our data indicate that L. mexicana
      CFAS modifies the fatty acid chain of plasmenylethanolamine (PME), the dominant
      class of ethanolamine glycerophospholipids in Leishmania, generating CFA-PME.
      While the endogenous level of CFA-PME is extremely low in wild type L. mexicana,
      overexpression of CFAS results in a significant increase. CFAS-null mutants (cfas
      ) exhibit altered cell shape, increased sensitivity to acidic pH, and aberrant
      growth in serum-free media. In addition, the CFAS protein is preferentially
      expressed during the proliferative stage of L. mexicana and is required for the
      cell membrane targeting of lipophosphoglycan. Finally, the maturation and
      localization of CFAS protein are dependent upon the downstream sequence of the
      CFAS coding region. Without the downstream sequence, the mis-localised CFAS
      protein cannot fully rescue the defects of cfas-. Our data suggest that CFA
      modification of phospholipids can significantly affect the parasite's response to
      certain adverse conditions. These findings are distinct from the roles of CFAS in
      L. infantum, highlighting the functional divergence in lipid modification among
      Leishmania spp.

PMID- 29180120
TI  - Reply to the editor- Disseminated intravascular coagulation as a cause of shock
      related to device extraction.

PMID- 29180121
TI  - To the Editor- Disseminated intravascular coagulation as a cause of shock related
      to device extraction.

PMID- 29180122
TI  - Use of the SAMe-TT2R2 score to predict anticoagulation control in atrial
      fibrillation and venous thromboembolism patients receiving vitamin K antagonists:
      A review.
AB  - Identifying patients who are likely to achieve and maintain a therapeutic
      international normalized ratio when prescribed a vitamin K antagonist for stroke
      prevention in atrial fibrillation (AF) and venous thromboembolism (VTE) is
      challenging. The SAMe-TT2R2 score was developed on the basis of common clinical
      factors that can highlight patients who may be unable to achieve and maintain
      good anticoagulation control and for whom a "trial of warfarin" would be
      inadvisable. This review summarizes the main published prospective and
      retrospective studies that have validated the SAMe-TT2R2 score in patients with
      AF and VTE treated with a vitamin K antagonist and how the SAMe-TT2R2 score could
      aid clinical decision making; 19 studies were included. Taken together,
      validation studies suggest that the SAMe-TT2R2 score is able to predict good or
      poor anticoagulation control in patients with AF and VTE, although data on
      patients with VTE are limited (3 studies). The available evidence suggests that
      the SAMe-TT2R2 score may be a useful tool to aid clinical decision making for
      oral anticoagulants in patients with AF and VTE.

PMID- 29180123
TI  - Childhood- versus adult-onset ANCA-associated vasculitides: A nested, matched
      case-control study from the French Vasculitis Study Group Registry.
AB  - OBJECTIVE: To investigate differences between childhood-onset ANCA-associated
      vasculitides (cAAVs) and matched adult-onset controls (aAAVs). METHODS: cAAV
      clinical pictures at onset and outcomes were compared to a randomly selected
      sample of aAAV patients from the French Vasculitis Study Group Registry. Cases
      and controls were matched for AAV (granulomatosis with polyangiitis [GPA],
      microscopic polyangiitis [MPA] or eosinophilic granulomatosis with polyangiitis
      [EGPA]), sex and year of enrollment. Medications, disease activity and damage
      were prospectively recorded. Kaplan-Meier curves and the log-rank test were used
      to analyze case-vs.-control differences for predefined outcomes. RESULTS:
      Comparing 35 cAAVs (25 GPA, 4 MPA, 6 EGPA) to 151 aAAVs (106 GPA, 17 MPA, 28
      EGPA), their respective median follow-up durations were 71 and 64months (P=0.49),
      and, at baseline, children had less frequent myalgias (P=0.005) and peripheral
      neuropathy (P<0.001) but were more frequently febrile (P<0.05). Rates of renal
      involvement were comparable (13 [37%] cAAVs vs. 73 [48%] aAAVs; P=0.31). Initial
      GPA-associated ischemic abdominal pain and nasal cartilage damage were more
      common in cAAVs than aAAVs (P<0.05). During follow-up, the cAAV relapse rate was
      higher (24.5 vs. 18.7 flares per 100 patient-years; P<0.05) and, at last visit,
      cases had accumulated more damage, mostly ear, nose & throat sequelae (P=0.001),
      associated with longer maintenance therapy (P=0.03), than aAAV controls. Four
      (11.4%) cAAV and 13 (8.6%) aAAV patients died (P=0.53). CONCLUSION: cAAVs are
      severe diseases, characterized by a higher relapse rate, more accrued damage and
      longer maintenance therapy than for aAAVs.

PMID- 29180124
TI  - NK cells in autoimmune diseases: Linking innate and adaptive immune responses.
AB  - The pathogenesis of autoimmunity remains to be fully elucidated, although the
      contribution of genetic and environmental factors is generally recognized.
      Despite autoimmune conditions are principally due to T and B lymphocytes, NK
      cells also appear to play a role in the promotion and/or maintenance of altered
      adaptive immune responses or in peripheral tolerance mechanisms. Although NK
      cells are components of the innate immune system, they shows characteristics of
      the adaptive immune system, such as the expansion of pathogen-specific cells, the
      generation of long-lasting "memory" cells able to persist upon cognate antigen
      encounter, and the possibility to induce an increased secondary recall response
      to re-challenge. Human NK cells are generally identified as CD56+CD3-, conversely
      CD56+CD3+ cells represent a mixed population of NK-like T (NK T) cells and
      antigen-experienced T cells showing the up-regulation of several NK cell markers.
      CD56dim constitute about 90% of NK cells in the peripheral blood, they are mature
      and involved in cytotoxicity responses; CD56bright instead are more immature,
      mostly involved in cytokine production, having only a limited role in cytolytic
      responses, keen to leave the blood vessels as the principal population observed
      in lymph nodes. NK cells have been identified also in non-lymphoid tissues since,
      in pathologic conditions, they can quickly reach the target organs. A cross-talk
      between NK with dendritic cells and T cells is established throughout different
      receptor-ligand bindings. Several studies support the correlation between NK cell
      number and/or functional alterations, such as a defective cytotoxic activity and
      several autoimmune conditions. Among the different autoimmune pathologies and
      even within the same disease, NK cell function is significantly different either
      promoting or even protecting against the onset of the autoimmune condition. In
      this Review, we discuss recent literature supporting the role played by NK cells,
      as a bridge between innate and adaptive immunity, in the onset of autoimmune
      diseases.

PMID- 29180125
TI  - Clinical and microbiological characteristics of the infections in patients
      treated with rituximab for autoimmune and/or malignant hematological disorders.
AB  - INTRODUCTION: Rituximab is commonly used for the treatment of hematological
      malignancies and autoimmune diseases. Despite a reputation for good tolerance,
      case-series and registries reported rituximab-related infections of variable
      severity including opportunistic infections. We aimed at describing the natural
      history of infectious events (IE) after treatment by rituximab providing clinical
      and microbiological features and outcome. PATIENTS AND METHODS: We
      retrospectively analyzed the medical records of patients treated with rituximab
      in an internal medicine department of a tertiary hospital between 2007 and 2015,
      and identified all IE after this therapy. Events' severity was assessed using the
      Common Terminological Criteria of Adverse Events (version 4.3) definitions.
      RESULTS: Among 101 patients treated with rituximab, we identified 228 IE in 74
      (73.3%) of these patients (median follow-up 30.4months). Indication for rituximab
      was either autoimmune disease (AID) (52.5% of patients), or monoclonal
      hematological disease (MHD) (47.5%). Patients received an overall median number
      of 5 rituximab infusions [interquartile range: 4-8], representing a cumulative
      dose of 4340mg [2620-6160]. After last rituximab infusion, IE occurred after
      3.1months [0.7-9.4]. Respectively, IE were severe in 28.1% of cases in patients
      treated for AID vs 58.0% in patients treated for MHD (p<0.001), due to
      opportunistic pathogens in 7.8% vs 11.0% (p=0.49) and fatal in 4.7% vs 13.0%
      (p=0.044). Factor associated with mortality were polymicrobial infection
      (p<0.001), monoclonal hematological disease (p=0.035), use of steroids over
      10mg/d within the last two weeks (p=0.003), and rituximab cumulative dose
      (p<0.001). We identified a group of 10 patients (9.9%) showing life-threatening,
      polymicrobial, and opportunistic infections constituting a 'catastrophic
      infectious syndrome', which was lethal in 7 cases. CONCLUSION: IE after treatment
      by rituximab can be extremely severe, especially in patients immunocompromised by
      several other drugs. Further studies should focus on the group with life
      threatening polymicrobial infections.

PMID- 29180126
TI  - Belimumab in the treatment of systemic lupus erythematous: An evidence based
      review of its place in therapy.
AB  - INTRODUCTION: Systemic lupus erythematous is an autoimmune disease with diverse
      clinical features and has its development associated with a complexity of
      genetic, hormonal and environmental factors and the development of
      autoantibodies. Identification of new treatments is currently an area of intense
      investigation. Belimumab is the first biologic approved for the treatment of the
      disease inhibiting the excessive B cell activity observed in these patients and
      consequently reduction of autoantibodies. AIM: To review the current transition
      of the evidence available of its use in real life patients with persistent active
      disease while on conventional therapies. EVIDENCE: The results observed on the
      large series of patients (over 50 patients) followed for at least six months
      confirm the observations from phase 3 trials. In clinical practice close to two
      third of the patients remained on belimumab and one third discontinued mostly due
      to evaluation by the doctor or the patient or both of no detectable positive
      response. The presence of adverse events was considerably low and the subgroups
      with skin and joint manifestations appear to benefit the most. Daily steroid use
      is usually reduced to a significantly low when compared with the intake before
      introduction of the biologic Although not seen on trials in real life the
      addition of belimumab to the conventional therapy in lupus nephritis is being
      reported in several patients. Cost of the medication is still an issue that
      hampers its use. Further evidence of its use in certain specific groups is under
      investigation and its results should shed light on additional indications. PLACE
      IN THERAPY: Considering what is currently published on the evidence here reviewed
      in the use of belimumab in clinical practice it is our understanding that
      belimumab it will be gradually incorporated in the armamentarium of treatment not
      necessarily on refractory patients. We believe that with the upcoming of the
      subcutaneous route in the near future should also help in widen the use of the
      belimumab to be considered in first line combination set ups.

PMID- 29180127
TI  - Curcumin: A natural modulator of immune cells in systemic lupus erythematosus.
AB  - Curcumin is a polyphenol natural product isolated from turmeric, interacting with
      different cellular and molecular targets and, consequently, showing a wide range
      of pharmacological effects. Recent preclinical and clinical trials have revealed
      immunomodulatory properties of curcumin that arise from its effects on immune
      cells and mediators involved in the immune response, such as various T-lymphocyte
      subsets and dendritic cells, as well as different inflammatory cytokines.
      Systemic lupus erythematosus (SLE) is an inflammatory, chronic autoimmune
      mediated disease characterized by the presence of autoantibodies, deposition of
      immune complexes in various organs, recruitment of autoreactive and inflammatory
      T cells, and excessive levels of plasma proinflammatory cytokines. The function
      and numbers of dendritic cells and T cell subsets, such as T helper 1 (Th1),
      Th17, and regulatory T cells have been found to be significantly altered in SLE.
      In the present report, we reviewed the results of in vitro, experimental (pre
      clinical), and clinical studies pertaining to the modulatory effects that
      curcumin produces on the function and numbers of dendritic cells and T cell
      subsets, as well as relevant cytokines that participate in SLE.

PMID- 29180128
TI  - Type B Pigmentary Demarcation Lines in Pregnancy.

PMID- 29180129
TI  - Genetic diagnosis of epidermolysis bullosa: recommendations from an expert
      Spanish research group.
AB  - Epidermolysis bullosa (EB) is a rare genetic disease that causes mucocutaneous
      fragility. It comprises a clinically and genetically heterogeneous group of
      disorder characterized by spontaneous or contact/friction-induced blistering. EB
      is classified into 4 types-simplex, junctional, dystrophic, and Kindler syndrome
      and 30 subtypes. The disease is caused by defects in proteins implicated in
      dermal-epidermal adhesion. At least 19 genes have been characterized and more
      than 1000 mutations identified, thus rendering diagnosis complex. Molecular
      diagnosis of EB is the last stage of a laborious process that starts with a
      detailed clinical history compilation and careful procurement of a skin fresh
      biopsy that includes an area where the epidermis detaches from the dermis. The
      detachment area makes it possible to establish the cleavage plane by antigen
      mapping and, in the best scenario, to identify a single candidate gene to search
      for pathogenic mutations. The results of the molecular diagnosis enable the
      physician to provide appropriate genetic counseling (inheritance pattern, risk of
      recurrence, and options for prenatal and preimplantation diagnosis) and implement
      subsequent preventive programs, as well as to establish a reasonable clinical
      prognosis facilitating access to specific therapy and rehabilitation. Lastly,
      molecular diagnosis is essential for the participation of patients in clinical
      trials, a critical issue given the current incurable status of EB. The present
      guidelines aim to disseminate the procedure for diagnosing EB in our laboratory
      and thus avoid suboptimal or incomplete clinical diagnoses. The recommendations
      we provide are the result of more than 10 years' experience in the molecular
      diagnosis of EB in Spain.

PMID- 29180130
TI  - Factors associated with low levels of physical activity among elderly residents
      in a small urban area in the interior of the Brazilian Amazon.
AB  - The aim of the present study was to investigate levels of physical activity and
      risk factors for inactivity in older adults living in an urban area in the
      interior of the Amazonas state, Brazil. Data were collected between 2013 and 2015
      from 274 individuals 60 years of age or older who resided in the interior of the
      Brazilian Amazon. Sociodemographic, general health, functional capacity and
      physical performance were associated with self-referred physical activity level.
      A multivariate analysis, after adjustment, showed that being a man, having a body
      mass index above 27kg/m2, never having lived in riverside communities and having
      less than three associated chronic diseases were independent risk factors for low
      levels of physical activity among elderly residing in the interior of the
      Brazilian Amazon. Few studies have been conducted about the characteristics that
      are singular to this population. Our results suggest that the physical activity
      level and, consequently, the aging process of the elderly is influenced by where
      they have resided throughout their lives. Additionally, the results showed
      particular risk factors associated with low physical activity level among older
      adults residing in the interior of the state of Amazonas.

PMID- 29180131
TI  - Impact of coexisting overactive bladder in Medicare patients with osteoporosis.
AB  - BACKGROUND: Osteoporosis and overactive bladder (OAB) are prevalent conditions in
      older adults and are independent risk factors for falls and fractures. A paucity
      of evidence exists examining the impact of coexisting OAB in patients with
      osteoporosis. OBJECTIVE: To examine the impact of OAB on healthcare resource
      utilization (HRU), clinical outcomes, and healthcare costs among older adult
      patients with osteoporosis. METHODS: This retrospective analysis compared
      patients with osteoporosis with and without OAB. Patients with an osteoporosis
      diagnosis, enrolled in a Medicare Advantage plan, and aged 65-89 inclusive were
      eligible. Incident OAB among patients with prevalent osteoporosis was identified.
      A comparison group of patients with osteoporosis but no evidence of OAB was
      propensity score matched on baseline characteristics. Fall and/or fracture
      outcomes, HRU and healthcare costs were evaluated during 12 months of follow-up.
      Bivariate comparisons of outcomes were conducted. Ordinary least squared
      regression was used to examine the relationship between OAB and total healthcare
      costs. RESULTS: After matching, 5,526 patients in each group were included.
      Patients with osteoporosis and OAB demonstrated greater all-cause HRU across all
      encounter types compared to patients without OAB (all P values<0.001). Patients
      with osteoporosis and OAB had a greater frequency of any fall/fracture (17.7% vs.
      14.9%, P<0.001). Patients with osteoporosis and OAB had 35% greater all-cause
      total healthcare costs than patients without OAB (P<0.001). CONCLUSIONS: Patients
      with OAB and osteoporosis had significantly greater all-cause HRU and costs.
      Falls and fractures were significantly more common in patients with osteoporosis
      and OAB compared to patients with osteoporosis without OAB.

PMID- 29180132
TI  - The effect of intravitreal cholinergic drugs on motor control.
AB  - The retina bears embryological, neurochemical and functional similarities to the
      circadian and dopamine systems of the brain. Recent studies have shown that the
      intravitreal injection of minute quantities of L-dopa and of the melatonin
      receptor antagonist ML-23 have anti-Parkinsonian potential. Furthermore, it has
      been suggested that light therapy may be potentially useful in treating some
      aspects of Parkinson's disease (PD) and it is hypothesized that this treatment
      works via the circadian system. Given that little is known about the mechanism by
      which such treatments work the present study was designed to examine the role of
      the acetyl cholinergic system of the retina in gross bodily movement. While IVIT
      atropine was shown to improve movement in intact rats Cogentin treated rats
      showed impairment of motor function compared to control rats or to rats treated
      with any other cholinergic drug. Furthermore, a link between the phase of the
      light/dark cycle and the efficacy of these drugs in altering movement was
      demonstrated. These results show that anticholinergic systems in the retina can
      exert control over movement which has been solely attributed to the function of
      deep brain structures.

PMID- 29180133
TI  - Cognitive, neurohistological and mortality outcomes following the four-vessel
      occlusion/internal carotid artery model of chronic cerebral hypoperfusion: The
      impact of diabetes and aging.
AB  - Chronic cerebral hypoperfusion (CCH) may be involved in the etiology of aging
      related dementias, and several risk factors contribute to their development
      and/or aggravation. We previously reported on the development of the 4-VO/ICA
      model of CCH, and the impact of hypertension on the cognitive and histological
      outcomes of CCH. Here, we advanced those studies by investigating how 4-VO/ICA
      alone or in combination with diabetes affects survival, body weight and cognitive
      performance in both young and middle-aged rats. Subsequently, middle-aged rats
      were examined for the impact of diabetes on CCH-induced neurodegeneration, white
      matter damage, and glial cells response. Diabetes alone reduced body weight and
      increased mortality rate slightly in young rats; these effects were striking,
      however, in the older animals. After CCH alone, neither body weight nor mortality
      rate changed significantly in both age groups. However, when CCH was combined
      with diabetes, mortality rate increased significantly in both aged groups. Young
      rats were cognitively asymptomatic to CCH, but they became 'mildly' impaired
      after CCH combined with diabetes. In middle-aged rats, CCH severely impaired
      memory, which was significantly worsened by diabetes. Moreover, diabetes
      aggravated neurodegeneration in the hippocampus and white matter injury in the
      corpus callosum and it promoted glial activation in the hippocampus and white
      matter of CCH middle-aged rats. These data suggest that diabetes interacts
      synergistically with age and reduces the capacity of the brain to adequately
      respond to CCH and highlight the importance of associating risk factors in the
      preclinical investigation of age-related cerebrovascular diseases physiopathology
      and potential therapies.

PMID- 29180134
TI  - Learning and memory are impaired in the object recognition task during
      metestrus/diestrus and after sleep deprivation.
AB  - Females are an under-represented research model and the mechanisms through which
      sleep loss impairs cognition are not clear. Since levels of reproductive hormones
      and the estrous cycle are sensitive to sleep loss and necessary for learning and
      memory, we hypothesized that sleep deprivation impacts learning and memory in
      female mice by interfering with the estrous cycle. We used the object recognition
      task to assess learning and memory in female mice during separate phases of the
      estrous cycle and after sleep loss. Mice in metestrus/diestrus attended to sample
      objects less than mice in proestrus/estrus during object acquisition, the first
      phase of the object recognition task. Subsequently, during the recognition phase
      of the task, only mice in proestrus/estrus displayed a preference for the novel
      object. Sleep deprivation for 12h immediately before the object recognition task
      reduced time attending to sample objects and novel object preference for mice in
      proestrus/estrus, without changing length of the estrous cycle. These results
      show that sleep deprived mice in proestrus/estrus had learning deficits and
      memory impairments, like mice in metestrus/diestrus. Since sleep deprivation did
      not disrupt the estrous cycle, however, results did not support the hypothesis.
      Cognitive impairments due to acute sleep loss were not due to alterations to the
      estrous cycle.

PMID- 29180135
TI  - Alpha-Synuclein transgenic mice, h-alpha-SynL62, display alpha-Syn aggregation
      and a dopaminergic phenotype reminiscent of Parkinson's disease.
AB  - Alpha-Synuclein (alpha-Syn) accumulation is considered a major risk factor for
      the development of synucleinopathies such as Parkinson's disease (PD) and
      dementia with Lewy bodies. We have generated mice overexpressing full-length
      human alpha-Syn fused to a membrane-targeting signal sequence under the control
      of the mouse Thy1-promotor. Three separate lines (L56, L58 and L62) with similar
      gene expression levels, but considerably heightened protein accumulation in L58
      and L62, were established. In L62, there was widespread labelling of alpha-Syn
      immunoreactivity in brain including spinal cord, basal forebrain, cortex and
      striatum. Interestingly, there was no detectable alpha-Syn expression in
      dopaminergic neurones of the substantia nigra, but strong human alpha-Syn
      reactivity in glutamatergic synapses. The human alpha-Syn accumulated during
      aging and formed PK-resistant, thioflavin-binding aggregates. Mice displayed
      early onset bradykinesia and age progressive motor deficits. Functional
      alterations within the striatum were confirmed: L62 showed normal basal dopamine
      levels, but impaired dopamine release (upon amphetamine challenge) in the dorsal
      striatum measured by in vivo brain dialysis at 9 months of age. This impairment
      was coincident with a reduced response to amphetamine in the activity test. L62
      further displayed greater sensitivity to low doses of the dopamine receptor 1
      (D1) agonist SKF81297 but reacted normally to the D2 agonist quinpirole in the
      open field. Since accumulation of alpha-Syn aggregates in neurones and synapses
      and alterations in the dopaminergic tone are characteristics of PD, phenotypes
      reported for L62 present a good opportunity to further our understanding of motor
      dysfunction in PD and Lewy body dementia.

PMID- 29180136
TI  - Obstacle circumvention and eye coordination during walking to least and most
      affected side in people with Parkinson's disease.
AB  - BACKGROUND: The mechanisms that contribute to gait asymmetry in people with
      Parkinson's disease (PD) are unclear, mainly during gait with greater
      environmental demand, such as when an obstacle is circumvented while walking.
      OBJECTIVE: The aim of this study was to investigate the effects of obstacle
      circumvention of the least and most affected side on motor and gaze behavior in
      people with PD under/without the effects of dopaminergic medication. METHODS:
      Fifteen people with PD and 15 matched-control individuals were instructed to walk
      along a pathway, at a self-selected velocity, and to circumvent an obstacle,
      avoiding contact with it. Each participant performed five trials for each side.
      Kinematic parameters, mediolateral and horizontal body clearance to the obstacle,
      strategy to circumvent the obstacle, and gaze behavior were calculated.
      Parameters were grouped according to the side that the obstacle was circumvented
      and compared by three-way ANOVAs. RESULTS: Both people with PD and the control
      group presented asymmetry to circumvent an obstacle during walking, however this
      was exacerbated in people with PD. Individuals with PD presented safe strategies
      (largest mediolateral and horizontal body clearance to the obstacle, "lead-out"
      strategy, and higher number and time of fixations on the obstacle) during
      obstacle circumvention for the least affected side compared to the most affected
      side. In addition, positive effects of dopaminergic medication on body clearance,
      spatial-temporal parameters, and gaze behavior were evidenced only when the
      obstacle was circumvented to the least affected side. CONCLUSIONS: The obstacle
      circumvention to the most affected side is risky for people with PD.

PMID- 29180138
TI  - Estimation of sex in a contemporary Saudi population based on sternal
      measurements using multidetector computed tomography.
AB  - Sex estimation is an essential step for identifying unknown individuals and
      usually depends on the presence of highly dimorphic bones, such as the pelvis and
      skull. Nevertheless, the body integrity can be compromised in certain
      circumstances, and these bones might be absent; therefore, the ability to use
      other bones for sex estimation is crucial. The aims of this study were to collect
      baseline data for sternal dimensions in Saudi adults, assess the existence of
      sexual dimorphism in the sternum, and generate population-specific equations to
      estimate sex using sternal dimensions. During 2014-2015, 200 thoracic/thoraco
      abdominal computed tomography (CT) images (100 men, 100 women) were anonymously
      collected from King Abdulaziz Medical City. Six measurements were obtained and
      two indices calculated after 3D reconstruction of the CT scans. Descriptive
      statistics were calculated, and sexual dimorphism was assessed using independent
      t-tests. Discriminant function equations were developed for these measurements.
      Except for the sternal index, men had significantly larger dimensions than women.
      Sexual dimorphism was highly significant (p<0.001). The best predictor was the
      combination of the manubrium and sternal body lengths (89.5%). In the stepwise
      analysis, the best predictors were the manubrium length, sternal body length,
      manubrium width, and corpus width at the first sternebra, with a cross-validated
      accuracy of 90.5%. Cross-validated accuracy for all measurements ranged between
      62.5% and 90.5%. The findings of the study may have important anatomical,
      anthropological, and forensic applications.

PMID- 29180137
TI  - The influence of early life stress on the integration of emotion and working
      memory.
AB  - INTRODUCTION: Early life stress (ELS) impacts emotional and cognitive
      competences. We aimed to investigate whether the effects of ELS on working memory
      (WM) performance depend on the valence of the stimuli. METHODS: Between January
      and October 2015, we recruited (N=31) healthy subjects with (N=15) and without
      (N=16) ELS experiences. Participants performed a WM-task with emotional stimuli.
      RESULTS: Results show a trend towards decreased WM accuracy in subjects with ELS
      experiences (p=.06) with increased WM accuracy (p=.08) and an altered pattern of
      BOLD responses in the left posterior cingulate cortex (PCC)/precuneus (p<.001)
      and the rostral anterior cingulate cortex (rACC) (p<.01) in response to negative
      stimuli. LIMITATIONS: The small sample size and potential confounding factors
      should be considered when interpreting the results. CONCLUSION: Our data suggests
      that negative valence influences cognitive performance and brain activity in
      subjects with ELS experiences.

PMID- 29180139
TI  - Combined gastrin releasing peptide-29 and glucagon like peptide-1 reduce body
      weight more than each individual peptide in diet-induced obese male rats.
AB  - To test the hypothesis that gastrin releasing peptide-29 (GRP-29) combined with
      glucagon like peptide-1 (7-36) (GLP-1 (7-36)) reduce body weight (BW) more than
      each of the peptides given individually, we infused the two peptides (0.5nmol/kg
      each) in the aorta of free feeding, diet-induced obese (DIO) male Sprague Dawley
      rats once daily for 25days and measured BW. We found that GRP-29 and GLP-1 reduce
      BW, GRP-29 reduced it more than GLP-1 and GRP-29+GLP-1 reduce BW more than each
      peptide given alone. This reduction was accompanied by decrease 24-hour food
      intake (normal rat chow), meal size (MS), duration of first meal and number of
      meals, and increase latency to the first meal, intermeal interval (IMI) and
      satiety ratio (IMI/MS, amount of food consumed per a unit of time). Furthermore,
      the peptides and their combination decreased 24-hour glucose levels. In
      conclusion, GRP-29+GLP-1 reduce BW more than each of the peptides given
      individually.

PMID- 29180140
TI  - Grit: An important characteristic in learners.
AB  - Grit, or the perseverance and passion for long-term goals, has been associated
      with successful pursuits in academics, competitions, and professions outside of
      pharmacy. The fortitude needed to withstand tremendous physical, mental, and
      emotional stressors may be better predicted by grit than other factors. In those
      who demonstrate grit, a combination of factors may reflect academic achievement.
      It appears that achievement results when talent and effort are combined, with
      particular attention being paid to effort, as it is a function of the direction,
      duration, and intensity of a person's actions toward a goal. It appears that grit
      may be a good discriminating factor when evaluating individuals in other
      professions. The objective of this short commentary is to provide an introduction
      to the non-pharmacy literature surrounding grit and to suggest its applications
      in pharmacy.

PMID- 29180141
TI  - Use of a health screening and education event to change student attitudes toward
      the elderly.
AB  - BACKGROUND: While many schools have incorporated geriatric pharmacy education
      into their curricula, questions remain as to how these experiences shape student
      perceptions of the geriatric population. The objective of this study was to
      assess student comfort levels and perceptions toward the geriatric patient
      population before and after participation in a single health screening and
      education event. METHODS: Student perceptions about the elderly (measured via the
      Geriatrics Attitude Survey) and comfort levels in caring for geriatric patients
      were assessed before and after an event. RESULTS: Twenty-two students completed
      pre-event and post-event surveys. Students were primarily female (73%), and half
      were completing their second year of pharmacy school (50%). Global student
      perceptions of geriatric patients positively changed from baseline following
      event participation (p = 0.023). Results reveal significant increases from
      baseline in student comfort levels with communicating, screening, and counseling
      elderly patients (p < 0.001, 0.01, and 0.001, respectively). CONCLUSION: The
      Geriatrics Attitude Survey is a useful tool in assessing the value of a geriatric
      experience. Participation in this geriatric experience caused a statistically
      significant positive change in global perception scores. Additionally, survey
      results indicate that interactions with geriatric patients at a single event
      increased student comfort in communication, screening, and counseling.

PMID- 29180142
TI  - The impact of proctored online exams on the educational experience.
AB  - PURPOSE: This study explored new ways to maintain academic integrity for large
      enrollment, completely online courses. We examined the use of ProctorU as our
      proctoring strategy with the objectives to identify any implementation challenges
      and understand the impact of using an online proctor on the student experience.
      METHODS: In fall 2013, students were surveyed after each exam. Based on these
      preliminary findings, ProctorU-related questions were included in the course
      evaluation administered in spring 2014. A mixed-methods analysis plan was used to
      examine the results, including quantitative analysis and qualitative analysis of
      open-ended survey questions. RESULTS: In the fall 2013 surveys, 88.95% of
      students reported being satisfied with their experience using ProctorU. Of those
      who were unsatisfied, following three emerging themes were identified: took too
      long to setup, technical difficulties, and personnel issues with proctors. In the
      spring 2014 course evaluation data, the majority of students rated the experience
      "good" (57.53%), but a large number of those same students also commented on
      issues they encountered. Over half of the students indicated that the use of
      ProctorU would influence their future decision to take another online course,
      either negatively or positively. CONCLUSIONS: The question of how to maintain
      academic integrity with online courses is still an ongoing question, but this
      project demonstrates that online proctoring does influence the educational
      experience in ways that must be considered when determining the risk and benefit
      balance of proctored and unproctored assessments.

PMID- 29180143
TI  - Development of a college-level assessment framework in line with international
      accreditation standards: A Middle Eastern perspective.
AB  - INTRODUCTION: Accreditation of international pharmacy programs by North American
      and European accrediting bodies is becoming increasingly popular. Practices
      regarding assessment and evaluation are especially highlighted in accreditation
      standards and many programs around the world do not currently have coordinated
      approaches to meet assessment expectations. This article describes the process of
      developing a comprehensive assessment framework at our institution and provides
      discussion regarding facilitators and barriers for those attempting to do the
      same. METHODS: A coordinator of Assessment and Accreditation was appointed by the
      Dean. This person subsequently formed an Assessment Committee consisting of
      faculty, student, and administrative support membership. This committee developed
      the assessment framework through a review of published and online literature, in
      addition to extraction of key assessment points from accreditation standards.
      These data were then categorized according to major domains informed by the
      literature review and subcategorized based on components to be assessed using
      consensus techniques. RESULTS: A comprehensive assessment framework was developed
      consisting of three domains (programmatic assessment, academics, and
      engagement/satisfaction). The components relating to programmatic assessment
      included vision/mission and accreditation standards; academics consisted of
      program learning outcomes, final cumulative assessment, and course and curriculum
      assessments; and engagement/satisfaction consisted of students, faculty/staff,
      and other stakeholders. CONCLUSION: An assessment framework guided by
      accreditation standards can coordinate assessment plans and support program
      quality.

PMID- 29180144
TI  - Predicting pharmacy students' intention to apply for a residency: A systematic
      theory of planned behavior approach.
AB  - OBJECTIVE: The current literature has identified many motivating factors and
      barriers influencing pharmacy students' decision to apply for residency training.
      Despite a growing need for residency trained pharmacists to advance the
      profession, it is not clear why only about one in four pharmacy students decide
      to pursue a residency, and which of these factors have the most influence on
      student decision-making. The study examines the factors associated with pharmacy
      students' intention to apply for a postgraduate residency using the theory of
      planned behavior (TPB) framework. METHODS: Second and third-year students from
      four Texas pharmacy schools were surveyed using an online questionnaire based on
      the TPB. Descriptive statistics and multiple linear regression analyses were
      utilized to assess the study objectives. RESULTS: A total of 251 completed
      responses were received. Attitude, subjective norms (SN), and perceived
      behavioral control (PBC) were significant predictors of intention to apply for a
      pharmacy residency (beta = 0.32, 0.58, and 0.36, respectively, p < 0.001).
      Attending ASHP's midyear meeting or other residency showcase was a significant
      predictor of intention (beta = 0.71, p = 0.006). Additional significant
      predictors of intention include believing a residency would increase confidence
      in practicing pharmacy (beta = 0.36, p < 0.001) and help achieve career goals
      (beta = 0.16, p < 0.02); the social influence of faculty members (beta = 0.10, p
      = 0.003) and family (beta = 0.08, p = 0.02); believing financial obligations
      (beta = 0.20, p = 0.006), feeling afraid of the competition and/or not matching
      (beta = 0.24, p < 0.001), needing to relocate (beta = 0.09, p = 0.04), and the
      lengthy application and/or interview process (beta = 0.12, p = 0.04) would make
      it more difficult to apply for a residency. CONCLUSIONS: The TPB model was useful
      in predicting pharmacy students' intention to apply for a residency, and all TPB
      constructs were significant predictors. Therefore, interventions that target
      students' attitude, SN, and PBC may be valuable to increase their intention,
      especially the specific beliefs identified to significantly predict intention.
      Future research into methods in which these motivating factors can be encouraged
      and perceived barriers can be addressed by pharmacy stakeholders will increase
      interest and participation in residency training.

PMID- 29180145
TI  - Design, analysis, and conclusions: Telling a consistent causal story.
AB  - Pharmacy educators are dedicated to providing the best education to student
      pharmacists and post-graduate trainees. This involves developing and evaluating
      new educational approaches or activities, as well as working to understand better
      other factors that may affect student and program outcomes. Although we may not
      realize it, the idea of causality, or the presence of a cause-and-effect
      relationship, is embedded in much of what we do when engaging in pharmacy
      educational scholarship. Saying that an educational intervention is effective at
      improving test scores implies that the intervention caused the increase. Perhaps
      more subtly, a cause-and-effect relationship is implied when identifying poor
      interviewing skills as a factor that reduces the likelihood that a student will
      obtain a pharmacy practice residency. The extent to which causal claims can be
      made depends on appropriate study design and analysis. Similarly, the language
      used to present these claims is related to study design and analysis.
      Unfortunately, study designs used when evaluating educational approaches do not
      always align with the language used to report the results. This review provides a
      brief overview of current thinking related to causal inference. The role of study
      design and analysis in causal inference is also discussed along with
      recommendations for study design and analysis to facilitate making appropriate
      causal claims. After reading this article, readers should be able to select a
      study design that best aligns with their particular research question and report
      their findings in ways that are faithful to the strengths of the study design.

PMID- 29180146
TI  - How-to-guide for writing multiple choice questions for the pharmacy instructor.
AB  - BACKGROUND: Writing multiple choice questions (MCQ) takes a lot of practice.
      Often, pharmacy practitioners lack the training to write effective MCQ. Sources
      for instruction in effective MCQ writing can be overwhelming with numerous
      suggestions of what should and should not be done. PURPOSE: The following guide
      is prepared to serve as a succinct reference for creation and revision of MCQ by
      both novice and seasoned pharmacy faculty practitioners. METHODS: The literature
      is summarized into 12 best practices for writing effective MCQ. Pharmacy specific
      examples that demonstrate violations of best practices and how they can be
      corrected are provided. IMPLICATIONS: The guide can serve as a primer to write
      new MCQ, as a reference to revise previously created questions, or as a guide to
      peer review of MCQ.

PMID- 29180147
TI  - Useful resources for members serving on a curriculum committee in schools and
      colleges of pharmacy.
AB  - The curriculum committee has an important role in the design and delivery of a
      Doctor of Pharmacy program. The primary purpose of this article is to identify
      relevant resources for members to utilize to be active participants in a school
      or college of pharmacy curriculum committee. The resources presented are focused
      around the following seven key curricular management concepts: orientation to
      curriculum, syllabus review, teaching methods, curriculum review,
      interprofessional education, student workload, and policy development, as these
      are common agenda items for a committee meeting. Several curricular resources
      used by other health care disciplines were included to promote collaboration with
      interprofessional education activities. Awareness of such resources may benefit
      members to achieve optimal educational outcomes for the program.

PMID- 29180148
TI  - Game on: The gamification of the pharmacy classroom.
AB  - BACKGROUND: Gamification is the use of game mechanics to promote engagement and
      enjoyment of problem-solving in non-game situations. Gamification has been used
      widely in recent years in industry and academia as a tool for training and
      education. OBJECTIVE: The aims of this paper are to provide an overview of
      gamification and digital game-based learning (DGBL), review the use of digital
      games in health professional education, and provide suggestions for future use in
      pharmacy curricula. DISCUSSION: Many examples of game-based learning in pharmacy
      and other health professional curricula have been published, however the body of
      literature on DGBL is less developed. Overall, evaluations of these techniques
      show that students find them engaging and enjoyable. A recent meta-analysis of
      studies comparing DGBL to non-game based learning in primary, secondary, post
      secondary education found that DGBL significantly enhances learning. Challenges
      to implementing game-based learning are financial, cultural, and technological.
      CONCLUSION: Many areas of the pharmacy curriculum could be appropriate for
      digital gamification. With more students entering pharmacy school familiar with
      video games and game-based living the time has come for pharmacy educators to
      explore how these instructional technologies could benefit a new generation of
      pharmacy students. As serious games are developed and researched in pharmacy
      curricula, test scores, student confidence in knowledge and skills, and retention
      of knowledge and skills are all outcomes that, if published, will help advance
      the adoption of DGBL into the pharmacy school classroom.

PMID- 29180149
TI  - Identifying motivators and barriers to student completion of instructor
      evaluations: A multi-faceted, collaborative approach from four colleges of
      pharmacy.
AB  - OBJECTIVE: To identify motivators and barriers to pharmacy student completion of
      instructor evaluations, and to develop potential strategies to improve the
      evaluation process. METHODS: Completed at four Ohio Colleges of Pharmacy, Phase I
      consisted of a student/faculty survey and Phase II consisted of joint
      student/faculty focus groups to discuss Phase I data and to problem solve.
      RESULTS: In Phase I, the top three student-identified and faculty-perceived
      motivators to completion of evaluations were to (1) make the course better, (2)
      earn bonus points, and (3) improve the instructor's teaching. The top three
      student-identified barriers to completion of evaluations were having to (1)
      evaluate multiple instructors, (2) complete several evaluations around the same
      time, and (3) complete lengthy evaluations. Phase II focus groups identified a
      number of potential ways to enhance the motivators and reduce barriers, including
      but not limited to making sure faculty convey to students that the feedback they
      provide is useful and to provide examples of how student feedback has been used
      to improve their teaching/the course. CONCLUSIONS: Students and faculty
      identified motivators and barriers to completing instructor evaluations and were
      willing to work together to improve the process.

PMID- 29180150
TI  - The impact of a research course on pharmacy students' perceptions of research and
      evidence-based practice.
AB  - BACKGROUND: Pharmacists need be able to understand and utilize evidence from the
      literature to provide optimal patient care as well as participate in research to
      improve care. Thus, it is important for pharmacy students to acquire skills in
      research and evidence-based practice (EBP). OBJECTIVES: To evaluate the changes
      in pharmacy student (1) perceptions of research and EBP, (2) interest in research
      participation, and (3) confidence in understanding the research process and
      developing a research proposal after completing a research course. METHODS: First
      year professional pharmacy students completed a required one-semester research
      course. Study objectives were assessed pre- and post-semester using a survey that
      contained seven demographic items, nine Research Perceptions items, and 17
      Confidence in Research items (5-point Likert scale; 1 = not at all confident, and
      5 = extremely confident). Two years of data were collected (2012: N = 49, 2013: N
      = 53) and analyzed using Wilcoxon signed-rank tests and Mann-Whitney U tests as
      appropriate. RESULTS: Significant improvements were seen in students' perceptions
      of the importance (2012: p = 0.022, 2013: p = 0.042) and usefulness of research
      (p = 0.022). Students' confidence significantly increased on all items for both
      years (p < 0.001). There was no significant change in student plans to perform or
      participate in future research. More students planned to use EBP in their
      practice post-semester in 2013 (p = 0.008). CONCLUSIONS: A research course can be
      an effective way to increase student confidence in research and improve
      perceptions on the importance and usefulness of research and EBP. It may not be
      an effective way to increase student interest in research as a career.

PMID- 29180151
TI  - Comparison of pharmacy students' knowledge and self-efficacy to provide cessation
      counseling for hookah and cigarette use.
AB  - OBJECTIVES: We aimed to assess pharmacy students' self-efficacy to provide
      cessation counseling for commercial cigarette and hookah tobacco use. METHODS: A
      cross-sectional study including PharmD students at a College of Pharmacy was
      conducted in Spring 2014. Confidence in counseling and perception of knowledge
      were self-rated and based on the Ask-Advise-Assess-Assist-Arrange follow-up
      (5A's) model and general tobacco cessation counseling skills. Comparisons were
      made between cigarettes and hookahs and by program level using t-tests, Wilcoxon
      signed-rank test, analyses of variance, and Tukey-Kramer tests. RESULTS: Overall,
      82% and 16% of the students, respectively, reported receiving training on
      cigarette smoking and hookah tobacco use cessation. Students were moderately
      confident in their ability to counsel. Compared to hookah tobacco use cessation
      counseling, students were more confident in their general counseling skills and
      ability to counsel on cigarette smoking cessation using the 5A's (p < 0.001 in
      each case). Students perceived themselves to be more knowledgeable about
      cigarette smoking cessation than about hookah tobacco use cessation. Almost half
      of the students (42.0%) thought hookah tobacco was less harmful than traditional
      cigarettes. CONCLUSIONS: Pharmacy students need further training to address
      hookah and other alternative tobacco products to support patients' cessation
      needs, decrease risks for tobacco-related morbidity and mortality, and increase
      medication effectiveness.

PMID- 29180152
TI  - Benefits of a concentrated teaching rotation: Perspectives of pharmacy residents
      and faculty.
AB  - The postgraduate pharmacy residency experience requires residents to develop the
      proper skillset to not only provide optimal therapeutic management to patients,
      but to effectively deliver their knowledge to trainees and other health care
      providers. Without specific recommendations for how to achieve these skills,
      residents may hone their communication, organizational, and teaching skills
      through a number of different venues currently offered by residency programs
      nationwide. Residency programs commonly offer a longitudinal experience in order
      for residents to obtain didactic teaching skills; less often do programs offer a
      concentrated rotation dedicated to academia. Residents can acquire a number of
      skills from a focused academic rotation including curriculum development, career
      growth, and preceptorship by following a schedule that more closely mimics that
      of a clinical faculty member. These skills are typically more difficult to
      develop with a longitudinal experience due to time constraints and other resident
      and faculty member commitments. Prior to implementing this experience, the impact
      on both the resident and faculty member should be taken into consideration.

PMID- 29180153
TI  - Adaptation and psychometric validation of a scale to assess student pharmacists'
      beliefs in simplifying complicated medication regimens.
AB  - OBJECTIVES: To validate a scale in order to identify the most relevant survey
      constructs to measure student pharmacists' beliefs of providing a novel cognitive
      service of simplifying complicated medication regimens of community dwelling
      patients using a pill card. METHODS: A pre-existing scale was used to construct
      an adapted questionnaire in the context of simplifying complicated drug regimens
      in patients taking >five Rx meds daily. The adapted 14-item questionnaire was
      administered to 126 student pharmacists immediately after they performed a
      mandatory community pharmacy advanced pharmacy practice experience (APPE)
      exercise to simplify complicated drug regimens of patients. All students had
      rehearsed this service with standardized patients before their APPEs assignment.
      In this APPE assignment the student pharmacists consolidated the dose timings of
      the daily medications while attempting to improve their likelihood of efficacy
      and reduce their risk of adverse events. The psychometric properties of the
      adapted questionnaire were assessed using parallel analysis and principal
      component analysis. Internal consistency was established using Cronbach's alpha.
      RESULTS: Out of 126 students, 116 (92%) responded to the questionnaire. Factor
      analysis produced a 3-factor solution of the 14-item scale which accounted for
      56% of the explained variance. The factors relate to self-efficacy (alpha =
      0.956), intention to practice (alpha = 0.89) and mattering (alpha = 0.885). The
      overall internal consistency as measured by Cronbach's alpha was 0.936. The mean
      values obtained using these scales were 6.01 +/- 0.823, 4.88 +/- 0.742, and 4.45
      +/- 0.556, respectively, indicating stronger beliefs in this cognitive service.
      CONCLUSIONS: The adapted 14-question instrument can be used to reliably measure
      the self-efficacy, intention and mattering of fourth-year student pharmacists who
      can simplify complicated drug regimens by consolidating routinely prescribed
      medications.

PMID- 29180154
TI  - Student use of flipped classroom videos in a therapeutics course.
AB  - PURPOSE: To evaluate the extent of student use of flipped classroom videos.
      METHODS: This was a cross-sectional study conducted in a college of pharmacy
      therapeutics course in the Unites States. In one section of the course (four
      sessions) all content was provided in the form of lecture videos that students
      had to watch prior to class. Class time was spent discussing patient cases. For
      half of the sessions, there was an electronic quiz due prior to class. The
      outcome measure was video view time in minutes. Adequate video view time was
      defined as viewing >=75% of total video duration. Video view time was compared
      with or without quizzes using the Wilcoxon signed-rank test. RESULTS: There were
      100 students in the class and all were included in the study. Overall, 74
      students had adequate video view time prior to session 1, which decreased to 53
      students for session 2, 53 students for session 3, and 36 students for session 4.
      Median video view time was greater when a quiz was required [80 minutes (IQR: 38
      114) versus 69 minutes (IQR: 3-105), p < 0.001]. The mean score on the exam was
      84 +/- 8 points (out of 100). There was a significant association between video
      view time (per 50% increment) and score on the exam (coefficient 2.52; 95% CI:
      0.79-4.26; p = 0.005; model R2 = 7.8%). CONCLUSION: Student preparation prior to
      the flipped classroom is low and decreases with time. Preparation is higher when
      there is a quiz required.

PMID- 29180155
TI  - The opinion of preceptors and students of very early IPPE rotations delivered
      concurrently with didactic courses.
AB  - INTRODUCTION: The Marshall University School of Pharmacy had the opportunity to
      create an experiential education program where IPPE education was introduced in
      their P1 year and was concurrent with didactic coursework. The School begins the
      delivery of experiential education as soon as the sixth week of the first
      professional year. OBJECTIVE: To ascertain the opinion of institutional
      preceptors, community preceptors, and students after the first academic year to
      discern viewpoints on the effectiveness and value of very early P1 experiential
      rotations. METHODS: Institutional and community preceptors and students were
      assessed by anonymous survey in order to ascertain their respective opinions
      regarding early P1 experiential education. The results of the preceptors were
      further divided into institutional and community practice sites. This study was
      approved by the Marshall University Institutional Review Board. RESULTS: Key
      findings demonstrated that early rotations were perceived as beneficial to the
      student by both community and institutional preceptors, as well as, the students
      themselves. CONCLUSIONS: Most, but not all, preceptors felt early rotations were
      beneficial to their practice and the student. Institutional preceptors were less
      likely to perceive a benefit to their practice or to the student than were
      community preceptors. Students were positive about the early experience. The
      results of these surveys regarding early experiential rotations should help
      minimize concerns of both preceptors and those assigned responsibility for
      constructing experiential programs about implementing early experiential
      rotations in the curriculum.

PMID- 29180156
TI  - Lesbian, gay, bisexual, and transgender inclusion: Survey of campus climate in
      colleges and schools of pharmacy.
AB  - BACKGROUND AND PURPOSE: To quantify the implementation of inclusive policies and
      benefits as well as institutional commitment to support LGBT faculty, staff, and
      students in pharmacy schools nationwide. EDUCATIONAL ACTIVITY AND SETTING: An
      anonymous, electronic survey was sent to administrators at 130 pharmacy schools.
      Forty-four survey responses were received, indicating a 34% response rate. The
      survey included questions relating to campus climate, inclusive policies and
      benefits, and institutional commitments to the LGBT community. FINDINGS:
      Approximately half of the survey respondents reported that their school has
      public written statements about diversity and multiculturalism that include
      sexual orientation and/or gender identity. About one-fifth of the respondents
      indicated that their school has inclusive materials for faculty, staff, and
      student information regarding sexual orientation and gender identity. Nearly one
      fourth of schools of pharmacy had participated in a voluntary LGBT training
      program, such as Safe Zone, Safe Space, or Ally Program. Over half of the
      respondents reported having access to LGBT organizations on campus, with two
      schools reporting having pharmacy organizations that specifically focus on LGBT
      student pharmacists and allies. Less than one-tenth of schools reported offering
      gender-neutral/single-occupancy restrooms and no schools reported knowledge of
      LGBT-related scholarships. SUMMARY: Room for improvement exists regarding the
      implementation of inclusive practices to improve campus climate for LGBT
      students, faculty, and staff. Areas with the largest room for improvement include
      accessible gender-neutral restrooms and availability of LGBT trainings,
      scholarships, and events.

PMID- 29180157
TI  - The development and piloting of "ATTEND DR," a clinical teaching tool to identify
      and prioritize potential causes of adverse drug reactions.
AB  - BACKGROUND: The identification, management, and reporting of adverse drug
      reactions are integral to clinical practice and education; however, undergraduate
      teaching related to adverse drug reactions may be inadequate for practice.
      Existing methods of causality assessment have a number of limitations in relation
      to clinical teaching, for example, they do not deal well with the concurrent use
      of other medications. OBJECTIVE: To develop and pilot a teaching tool to guide
      students through the process of identifying and prioritizing potential causes of
      an adverse drug reaction. SETTING: University-based School of Pharmacy,
      Australia: an undergraduate Quality Use of Medicines course. METHOD: A contrived
      acronym (mnemonic) was developed from causality assessments and discussions with
      practitioners. The acronym ATTEND DR (abnormality, taken, timeline, evidence,
      nothing else?, dose, dechallenge, and rechallenge) was piloted in workshops that
      focussed on adverse drug reactions and their management. Students' responses to
      "What did you find most valuable about today's workshop?" and "How could we
      improve?" were analyzed. RESULTS: All attendees responded (65/65). Students
      indicated that the ATTEND DR acronym was easy to remember, and facilitated
      causality assessment in a clinical context, due to an easily followed, step-by
      step, comprehensive process that was easy to remember. More practice case studies
      were requested. CONCLUSION: The ATTEND DR acronym was designed to address
      limitations of the existing methods of causality assessment in relation to
      clinical teaching and preparation of students for future clinical roles. Students
      responded favorably to its introduction, commenting that it was easily remembered
      and provided a comprehensive, clinically orientated, step-by-step process.

PMID- 29180158
TI  - Assessment of students' ability to incorporate a computer into increasingly
      complex simulated patient encounters.
AB  - BACKGROUND AND PURPOSE: Pharmacy students should be exposed to and offered
      opportunities to practice the skill of incorporating a computer into a patient
      interview in the didactic setting. Faculty sought to improve retention of student
      ability to incorporate computers into their patient-pharmacist communication.
      EDUCATIONAL ACTIVITY AND SETTING: Students were required to utilize a computer to
      document clinical information gathered during a simulated patient encounter
      (SPE). Students utilized electronic worksheets and were evaluated by instructors
      on their ability to effectively incorporate a computer into a SPE using a rubric.
      Students received specific instruction on effective computer use during patient
      encounters. Students were then re-evaluated by an instructor during subsequent
      SPEs of increasing complexity using standardized rubrics blinded from the
      students. FINDINGS: Pre-instruction, 45% of students effectively incorporated a
      computer into a SPE. After receiving instruction, 67% of students were effective
      in their use of a computer during a SPE of performing a pharmaceutical care
      assessment for a patient with chronic obstructive pulmonary disease (COPD) (p <
      0.05 compared to pre-instruction), and 58% of students were effective in their
      use of a computer during a SPE of retrieving a medication list and social history
      from a simulated alcohol-impaired patient (p = 0.087 compared to pre
      instruction). DISCUSSION: Instruction can improve pharmacy students' ability to
      incorporate a computer into SPEs, a critical skill in building and maintaining
      rapport with patients and improving efficiency of patient visits. Complex
      encounters may affect students' ability to utilize a computer appropriately.
      Students may benefit from repeated practice with this skill, especially with SPEs
      of increasing complexity.

PMID- 29180159
TI  - Pharmacy students' use and perceptions of Apple mobile devices incorporated into
      a basic health science laboratory.
AB  - OBJECTIVE: To describe pharmacy students' use of mobile devices in a basic health
      science laboratory and to report the students' perceptions on how solving cases
      with their mobile devices influenced their attitudes, abilities, and view on the
      use of mobile devices as tools for pharmacists. METHODS: First-year pharmacy
      students utilized mobile devices to solve clinical case studies in a basic health
      sciences laboratory. A pre-survey and two post-surveys were administered to
      assess the students' comfort, awareness, use, and perceptions on the use of their
      mobile devices and apps. RESULTS: The pre-survey and first post-survey each had a
      response rate of 99%, and the second post-survey had a response rate of 100%. In
      comparing the pre-survey and first post-survey data, there was a statistically
      significant increase in the number of students that agreed or strongly agreed
      that they were more comfortable utilizing their mobile device (p = 0.025), they
      were more aware of apps for pharmacists (p < 0.005), and they have used more apps
      that can be useful for pharmacists (p < 0.005). The second post-survey
      demonstrated that over 78% of students agreed or strongly agreed that completing
      the case studies influenced them to be more comfortable with their mobile
      devices, to be more aware of apps that can be useful for pharmacists, and to be
      more agreeable with mobile device utilization by pharmacists in improving patient
      care. In addition, the second post-survey also demonstrated that 84% of students
      responded that using their mobile devices to solve the cases influenced them to
      either use their mobile device in a clinical setting for a clinical and/or
      pharmacy-related purpose for the first time or to use it more frequently for this
      purpose. CONCLUSIONS: The use of mobile devices to solve clinical cases in a
      first-year basic health science laboratory course was perceived as beneficial by
      students and influenced them to utilize their mobile device even more in a
      pharmacy practice setting.

PMID- 29180160
TI  - Predictors of student performance on the Pharmacy Curriculum Outcomes Assessment
      at a new school of pharmacy using admissions and demographic data.
AB  - OBJECTIVES: To characterize student performance on the Pharmacy Curriculum
      Outcomes Assessment (PCOA) and to determine the significance of specific
      admissions criteria and pharmacy school performance to predict student
      performance on the PCOA during the first through third professional years.
      METHODS: Multivariate linear regression models were developed to study the
      relationships between various independent variables and students' PCOA total
      scores during the first through third professional years. RESULTS: To date, four
      cohorts have successfully taken the PCOA examination. Results indicate that the
      Pharmacy College Admissions Test (PCAT), the Health Science Reasoning Test
      (HSRT), and cumulative pharmacy grade point average were the only consistent
      significant predictors of higher PCOA total scores across all students who have
      taken the exam at our school of pharmacy. CONCLUSION: The school should examine
      and clarify the role of PCOA within its curricular assessment program. Results
      suggest that certain admissions criteria and performance in pharmacy school are
      associated with higher PCOA scores.

PMID- 29180161
TI  - Implementing professionalism by deprofessionalized strategies: A moral quandary.
AB  - Monetary fine proceedings has been one of the methods of upholding
      professionalism amongst health care professionals. Professionalism as a concept
      is multifaceted and fragmented and it has become symbolic to the extent that,
      unfortunately, some traits of professionalism showcase the whole concept. It
      seems fair to interpret the symbolic views on the concept of professionalism as
      means to capitalize on certain aspects of professions such as commercial
      profitability for the employer and respected status for the profession.
      Evaluation of professionalism is often implicit and inadequate; and assessing
      professionalism by relying on abstract and idealized definitions implies that
      professionalism is a compounded composite of certain set of stable traits. We
      suggest to refer to the theory of values-based practice so as to achieve
      collocated views on professionalism among employers and health academics. Instead
      of capitalizing on certain traits of professionalism to project the whole concept
      of professionalism, we may need to relook at the traits of professionalism as
      values. It is extremely crucial to internalize the values of the health
      profession in the future health professionals, so that the future health
      professionals imbibe the professionalism through dialog and democratic methods of
      sharing values during the course of professional development.

PMID- 29180162
TI  - Using a community theatre as a self-directed introductory pharmacy practice
      experience (SD IPPE) site.
AB  - OBJECTIVE: To describe a novel setting and method for self-directed introductory
      pharmacy practice experiences (SD IPPE). METHODS: Students presented health care
      information relative to the plot of a production at a local community theater
      throughout the season. Students developed a poster and handout that were
      presented in the theater lobby prior to each production. ASSESSMENT: A six
      question survey was provided to students after each presentation that identified
      their perceived benefit to play patrons and their overall experience using a 5
      point Likert scale. IMPLICATIONS: Completing SD IPPE in a theater is a novel and
      innovative concept. Data suggest that students prefer presenting information in
      non-traditional settings. Students felt their work enhanced the theatrical
      experience of patrons. Results demonstrate that the theater is a viable setting
      for future presentations that benefit both students and public.

PMID- 29180163
TI  - A needs assessment of pharmacokinetic skills performed on advanced pharmacy
      practice experiences by student pharmacists.
AB  - INTRODUCTION: Pharmacokinetic (PK) calculations are an important competency for
      pharmacy students, however, there is little to guide which medications should be
      included in pharmacy curricula. Additionally, many new medications require
      therapeutic drug monitoring (TDM)-but not PK calculations-to ensure safe use. The
      objectives of this study were to quantify which medications are most frequently
      encountered by pharmacy students during advanced pharmacy practice experiences
      (APPE's) and to what extent PK calculations or TDM were completed by students
      while on APPE's at the University of New England. METHODS: Fourth-year students
      were surveyed upon completion of their advanced pharmacy practice experiences
      (APPE's). RESULTS: Pharmacokinetic calculations occurred most frequently on
      institutional rotations. Vancomycin and aminoglycosides were the two most common
      medications pharmacy students were asked to perform PK calculations for while on
      APPE's. Therapeutic drug monitoring occurred most frequently on institutional
      rotations. Therapeutic drug monitoring also occurred more often than
      pharmacokinetic monitoring on ambulatory care rotations. CONCLUSIONS:
      Pharmacokinetic calculations as well as therapeutic drug monitoring requiring no
      calculations were both commonly encountered by student pharmacists while on APPE
      rotations. Changes to clinical guidelines have impacted the types of medications
      students are expected to have proficiency with, and more broadly defined
      therapeutic drug monitoring competencies may be important for ambulatory care
      APPE's.

PMID- 29180164
TI  - Th-17 cytokines are associated with severity of Trypanosoma cruzi chronic
      infection in pediatric patients from endemic areas of Mexico.
AB  - In Chagas disease the clinical, acute and chronic manifestations are the result
      of the interaction between the parasite and the host factors. The balance between
      inflammatory and anti-inflammatory immune responses is essential for the increase
      or resolution of the manifestations in individuals infected with T. cruzi. To
      identify if children with chronic Chagas disease and heart injury is related with
      non-regulated Th1, Th2 and Th17 responses. We included 31 children with T. cruzi
      confirmed chronic infection from endemic areas of Mexico. Subsequently, they were
      separated according to their ECHO and ECG results into three groups according to
      the severity of cardiac involvement. Circulating Th1, Th2 and Th17 cytokine
      profiles were performed by Luminex assays and the results were analyzed by
      bivariate and multivariable analysis. Patients were classified in asymptomatic
      chronic (group 1, N=12); individuals with IRBBB in ECG and incipient lesions in
      ECHO (Group 2, N=8) and Patients with severe chronic symptomatic disease (Group
      3, N=11). The analysis of immune mediators revealed that patients with severe
      cardiac manifestations had significant higher levels (p <0.05) of Th17 related
      cytokines including IL-17 and IL-6 as well as IFN-gamma and IL-2. Also patients
      with severe cardiomyopathy exhibit increased levels of IL-13 (p <0.05) after
      multivariate analysis. High levels of Th17 related cytokines including IL-17, IFN
      gamma, IL-6 and IL-2 and pro-fibrotic factors such as IL-13 could be associated
      to the severity of cardiac involvement in children with chronic T. cruzi
      infection. These cytokines could be useful as indicators for the early
      identification of cardiac damage associated to the T. cruzi infection.

PMID- 29180165
TI  - Photolabile ruthenium complexes to cage and release a highly cytotoxic anticancer
      agent.
AB  - CHS-828 (N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N"-4-pyridyl guanidine) is an
      anticancer agent with low bioavailability and high systemic toxicity. Here we
      present an approach to improve the therapeutic profile of the drug using
      photolabile ruthenium complexes to generate light-activated prodrugs of CHS-828.
      Both prodrug complexes are stable in the dark but release CHS-828 when irradiated
      with visible light. The complexes are water-soluble and accumulate in tumour
      cells in very high concentrations, predominantly in the mitochondria. Both
      prodrug complexes are significantly less cyototoxic than free CHS-828 in the dark
      but their toxicity increases up to 10-fold in combination with visible light. The
      cellular responses to light treatment are consistent with release of the
      cytotoxic CHS-828 ligand.

PMID- 29180166
TI  - Highlights from the 20th Workshop on Vitamin D in Orlando, Mar. 28-31, 2017.

PMID- 29180167
TI  - Characterization of equine GST A3-3 as a steroid isomerase.
AB  - Glutathione transferases (GSTs) comprise a superfamily of enzymes prominently
      involved in detoxication by making toxic electrophiles more polar and therefore
      more easily excretable. However some GSTs have developed alternative functions.
      Thus, a member of the Alpha class GSTs in pig and human tissues is involved in
      steroid hormone biosynthesis, catalyzing the obligatory double-bond isomerization
      of Delta5-androstene-3,17-dione to Delta4-androstene-3,17-dione and of Delta5
      pregnene-3,20-dione to Delta4-pregnene-3,20-dione on the biosynthetic pathways to
      testosterone and progesterone. The human GST A3-3 is the most efficient steroid
      double-bond isomerase known so far in mammals. The current work extends
      discoveries of GST enzymes that act in the steroidogenic pathways in large
      mammals. The mRNA encoding the steroid isomerase GST A3-3 was cloned from testis
      of the horse (Equus ferus caballus). The concentrations of GSTA3 mRNA were
      highest in hormone-producing organs such as ovary, testis and adrenal gland.
      EcaGST A3-3 produced in E. coli has been characterized and shown to have highly
      efficient steroid double-bond isomerase activity, exceeding its activities with
      conventional GST substrates. The enzyme now ranks as one of the most efficient
      steroid isomerases known in mammals and approaches the activity of the bacterial
      ketosteroid isomerase, one of the most efficient enzymes of all categories known
      today. The high efficiency and the tissue distribution of EcaGST A3-3 support the
      view that the enzyme plays a physiologically significant role in the biosynthesis
      of steroid hormones.

PMID- 29180168
TI  - Inhalable particulate drug delivery systems for lung cancer therapy:
      Nanoparticles, microparticles, nanocomposites and nanoaggregates.
AB  - There is progressive evolution in the use of inhalable drug delivery systems
      (DDSs) for lung cancer therapy. The inhalation route offers many advantages,
      being non-invasive method of drug administration as well as localized delivery of
      anti-cancer drugs to tumor tissue. This article reviews various inhalable
      colloidal systems studied for tumor-targeted drug delivery including polymeric,
      lipid, hybrid and inorganic nanocarriers. The active targeting approaches for
      enhanced delivery of nanocarriers to lung cancer cells were illustrated. This
      article also reviews the recent advances of inhalable microparticle-based drug
      delivery systems for lung cancer therapy including bioresponsive, large porous,
      solid lipid and drug-complex microparticles. The possible strategies to improve
      the aerosolization behavior and maintain the critical physicochemical parameters
      for efficient delivery of drugs deep into lungs were also discussed. Therefore, a
      strong emphasis is placed on the approaches which combine the merits of both
      nanocarriers and microparticles including inhalable nanocomposites and
      nanoaggregates and on the optimization of such formulations using the proper
      techniques and carriers. Finally, the toxicological behavior and market potential
      of the inhalable anti-cancer drug delivery systems are discussed.

PMID- 29180169
TI  - Sarcopenia in children with perforated appendicitis.
AB  - BACKGROUND: Decreased skeletal muscle mass, or sarcopenia, has been shown to be
      associated with worse postoperative recovery and a higher risk of complications
      in adult surgical patients. We hypothesized that pediatric patients with
      complicated appendicitis may experience sarcopenic changes over the course of
      their treatment. METHODS: The medical records and computed tomography scans of 36
      pediatric complex appendicitis patients who had both preoperative and
      postoperative computerized tomography scans at our hospital were reviewed.
      Changes in psoas muscle area were examined using linear mixed models with random
      patient-level intercept and time effects. RESULTS: The median change in body mass
      index among all patients from admission to discharge was -0.8 kg/m2
      (interquartile range: -1.3 to -0.2). The mean percentage change in psoas muscle
      area per day over the course of appendicitis-related treatment was -0.81% (95%
      confidence interval: -1.12 to -0.50) (P < 0.001). The relative decrease in psoas
      muscle area per day did not vary by initial body mass index, gender, or race (P >
      0.10 for all interactions). CONCLUSIONS: Our data suggest that pediatric patients
      with complex appendicitis experience sarcopenic changes during their hospital
      admission. Given previous reports that sarcopenia is a significant predictor of
      worse surgical outcomes, more investigation is warranted to assess whether these
      changes are associated with postsurgical complications and to evaluate potential
      interventions that may prevent these changes.

PMID- 29180170
TI  - Money well spent? A cost and utilization analysis of prophylactic inferior vena
      cava filter placement in high-risk trauma patients.
AB  - BACKGROUND: Inferior vena cava filters (IVCF) for venous thromboembolic
      prophylaxis in high-risk trauma patients is a controversial practice. Utilization
      of IVCF prophylaxis was evaluated at a level 1 trauma center. Daily cost of IVCF
      prophylaxis, time to IVCF, duration between IVCF and chemoprophylaxis, and number
      of patients needed to treat (NNT) to prevent pulmonary embolism (PE) was
      calculated. METHODS: A retrospective review of prophylactic IVCF over a 5-year
      period (2010-2014). Demographic, physiologic, injury, procedural, and outcome
      data were abstracted from the administrative trauma database. Medicare fees and
      days without chemoprophylaxis were used to determine daily IVCF cost. NNT was
      calculated using PE events in a cohort without IVCF. RESULTS: Over the 5-year
      period, 146 patients with mean age 56.3 y (SD +/- 24.2), 67.8% male, underwent
      prophylactic IVCF. Predominant mechanisms of injuries were falls (45.9%) and
      motor vehicle accidents (20.5%) with median Injury Severity Score of 25
      (intraquartile range [IQR] 16-29) and head Abbreviated Injury Score of 3 (IQR 3
      5). Most common operative interventions required in 24.7% were orthopedic (25.3%)
      and neurosurgical (21.9%). Median time to IVCF was 78 h (IQR 48-144). Most common
      IVCF indications were closed head injury (48.6%) and spinal injuries (30.8%).
      Median time to administration of chemoprophylaxis was 96 h after IVCF (IQR 24
      192) in 57.5%. Median IVCF cost was $759/d (IQR $361-$1897) compared with $4.32
      for chemoprophylaxis. PE occurred in 0.26% without IVCF. PE did not occur with
      prophylactic IVCF. Estimated NNT was 379 (95% CI 265, 661). CONCLUSIONS:
      Prophylactic IVCF placement is a costly practice with relatively low benefit.
      Anticipated time without chemoprophylaxis and patient criteria should be
      considered before routine IVCF placement.

PMID- 29180171
TI  - The long-term outcomes of thyroid function after subtotal thyroidectomy for
      Graves' hyperthyroidism.
AB  - BACKGROUND: Surgical management of Graves' disease (GD) is changing from subtotal
      to total thyroidectomy because the latter eliminates the risk of recurrence.
      However, to preserve thyroid function in a euthyroid state, subtotal
      thyroidectomy is still performed for GD in non-Western countries. Therefore, we
      designed a study to investigate the long-term outcomes in GD patients after
      subtotal thyroidectomy and the correlation between remnant weight and
      postoperative thyroid function. MATERIALS AND METHODS: This was a retrospective
      cohort observation study. Between January 2005 and December 2011, 415 consecutive
      GD patients treated by subtotal thyroidectomy were enrolled. All data were
      collected from 385 patients who underwent bilateral subtotal thyroidectomy and 57
      patients who underwent the Hartley-Dunhill operation. The median postoperative
      follow-up time was 72 months (range 12-144 months). RESULTS: The mean weight of
      the preserved thyroid remnant was 5.1 g. Persistent or recurrent hyperthyroidism
      was observed in 119 (28.7%) patients. The median time of recurrence was 36 months
      (range 12-120 months). Hypothyroidism developed in over 50% of patients. A
      euthyroid state was achieved in only 19.3% of patients, and the rate did not
      increase significantly as remnant weight increased. Based on a Cox regression
      analysis, the remnant weight is an independent risk factor for persistent or
      recurrent hyperthyroidism (hazard ratio: 1.323, 95% confidence interval: 1.198
      1.461, P < 0.001). CONCLUSIONS: Subtotal thyroidectomy with the intent to
      maintain a euthyroid state is not an optimal surgical strategy for the definitive
      treatment of GD because the persistence or recurrence rate is high and the
      euthyroid rate is lower than expected.

PMID- 29180172
TI  - Early appendectomy reduces costs in children with perforated appendicitis.
AB  - BACKGROUND: Perforated appendicitis can be managed with early appendectomy, or
      nonoperative management followed by interval appendectomy. We aimed to identify
      the strategy with the lowest health care utilization and cost. METHODS: We
      retrospectively reviewed the medical records of all children <=18 years old with
      perforated appendicitis admitted to a single institution between January 2009 and
      March 2016. After excluding immunosuppressed patients and transfers from outside
      hospitals, we grouped the remaining patients by early or interval appendectomy.
      Cost accounting data were obtained from our institutional database. The primary
      outcome was total hospital cost over 2 y from initial admission for appendicitis.
      Other outcomes analyzed included initial admission costs, number of admissions,
      emergency room and clinic visits, percutaneous procedures, cross-sectional and
      overall imaging studies, and length of stay. RESULTS: A total of 203 children
      with perforated appendicitis were identified. After exclusion of immunosuppressed
      patients and outside hospital transfers, 94 patients were included in the study.
      Thirty-nine underwent early appendectomy and 55 initial nonoperative management;
      of these, 54 underwent elective interval appendectomy. Five of 55 patients (9%)
      failed initial nonoperative management and required earlier-than-planned
      appendectomy. Total cost over 2 y was significantly lower with early appendectomy
      than initial nonoperative management ($19,300 +/- 14,300 versus $26,000 +/-
      17,500; P = 0.05). Early appendectomy resulted in fewer hospital admissions,
      clinic visits, invasive procedures, and imaging studies. CONCLUSIONS: Early
      appendectomy results in lower hospital costs and less health care utilization
      compared with initial nonoperative management with elective interval
      appendectomy. A prospective study will shed more light on this question and can
      assess the role of nonoperative management without interval appendectomy in
      children with perforated appendicitis.

PMID- 29180173
TI  - Greater lymph node retrieval and lymph node ratio impacts survival in resected
      pancreatic cancer.
AB  - BACKGROUND: Surgical resection is the mainstay of pancreatic cancer treatment;
      however, the ideal lymphadenectomy remains unsettled. This study sought to
      determine whether number of examined lymph nodes (eLNs) and lymph node ratio
      (LNR) impact survival. METHODS: The U.S. National Cancer Data Base (2003-2011)
      was reviewed for patients who underwent initial resection for clinical stage I
      and II pancreatic adenocarcinoma. Univariate and multivariate survival analyses
      were performed. RESULTS: Of 14,007 patients, 15.6% had 0-6 eLN, 27.1% 7-12, 13.4%
      13-15, and 38.6% > 15 eLN. Median eLN was 11 for pancreaticoduodenectomy, and 14
      for distal, total pancreatectomy, or other procedure. ELN >15 was associated with
      significantly improved survival in both node negative and positive disease (P <
      0.001, both). In multivariable analysis, 7-12, 13-15, and >15 eLN had improved
      survival relative to 0-6 eLN (HR 0.87, P < 0.001, HR 0.89, P = 0.002, HR 0.82, P
      < 0.001, respectively). A total of 34.5% of patients had an LNR of 0, 31.5% <=
      0.2, 20.3% 0.2-0.4, 11.7% 0.4-0.8, and 2.0% had an LNR >0.8. Patients with LNR 0
      had improved survival in T1-T3 disease (P < 0.01). In multivariable analysis,
      higher LNR was negatively associated with survival (LNR 0-0.2: HR 1.44, P <
      0.001, LNR 0.2-0.4: HR 1.82, P < 0.001, LNR 0.4-0.8: 2.03, P < 0.001, LNR >0.8, P
      < 0.001). Even with suboptimal eLN (eLN <=6 or <=12), higher LNR remained an
      independent predictor of mortality. CONCLUSIONS: Greater lymph node retrieval in
      stage I & II pancreatic adenocarcinoma may have prognostic value, even in node
      negative disease. Lymph node ratio is inversely related to survival and may be
      useful with suboptimal eLN.

PMID- 29180174
TI  - Formalin-fixed paraffin-embedded sample conditions for deep next generation
      sequencing.
AB  - INTRODUCTION: Precision medicine is only possible in oncology practice if
      targetable genes in fragmented DNA, such as DNA from formalin-fixed paraffin
      embedded (FFPE) samples, can be sequenced using next generation sequencing (NGS).
      The aim of this study was to examine the quality and quantity of DNA from FFPE
      cancerous tissue samples from surgically resected and biopsy specimens. METHODS:
      DNA was extracted from unstained FFPE tissue sections prepared from surgically
      resected specimens of breast, colorectal and gastric cancer, and biopsy specimens
      of breast cancer. A total quantity of DNA >=60 ng from a sample was considered
      adequate for NGS. The DNA quality was assessed by Q-ratios, with a Q-ratio >0.1
      considered sufficient for NGS. RESULTS: The Q-ratio for DNA from FFPE tissue
      processed with neutral-buffered formalin was significantly better than that
      processed with unbuffered formalin. All Q-ratios for DNA from breast, colorectal
      and gastric cancer samples indicated DNA levels sufficient for NGS. DNA extracted
      from gastric cancer FFPE samples prepared within the last 7 years is suitable for
      NGS analysis, whereas those older than 7 years may not be suitable. Our data
      suggested that adequate amounts of DNA can be extracted from FFPE samples, not
      only of surgically resected tissue but also of biopsy specimens. CONCLUSIONS: The
      type of formalin used for fixation and the time since FFPE sample preparation
      affect DNA quality. Sufficient amounts of DNA can be extracted from FFPE samples
      of both surgically resected and biopsy tissue, thus expanding the potential
      diagnostic uses of NGS in a clinical setting.

PMID- 29180175
TI  - YouTube as a source of information for patients considering surgery for
      ulcerative colitis.
AB  - BACKGROUND: With the range of health information online, assessing the resources
      that patients access may improve the content of preoperative information. Our aim
      was to assess the content of the most viewed videos on YouTube related to surgery
      for ulcerative colitis (UC). METHODS: YouTube was searched for videos containing
      information on surgery for UC. The 50 most viewed videos were identified and user
      interaction analyzed. Upload source was classified as patient, individual health
      care professional (HCP), or hospital/professional association. Video content was
      categorized using an inductive thematic analysis on a purposive sample list of
      videos. The overarching theme of each video was classified once data saturation
      was achieved. RESULTS: Thirty videos were uploaded by patients, 15 by hospitals
      and 5 by HCPs. Seventeen videos (34%) discussed life after surgery. Sixteen of
      these were uploaded by patients who had previously undergone surgery for UC. No
      videos of this theme were uploaded by HCPs. Ten videos (20%) described a number
      of different operations. Other themes identified were alternative health
      therapies (12%), colonoscopy (12%), life with UC (8%), miscellaneous (8%), and
      education for HCPs (6%). Patient uploaded videos had significantly more comments
      (P = 0.0079), with 28% of comments on patient videos being users requesting
      further information. CONCLUSIONS: Understanding the sequelae of surgery is most
      important to preoperative patients. There are a lack of professional videos
      addressing this topic on YouTube. HCPs must participate in the production of
      videos and adapt preoperative consultations to address common preoperative
      concerns.

PMID- 29180176
TI  - Magnetic transcutaneous fixation: an experimental study in pigs.
AB  - BACKGROUND: Magnetic subdermal implants have never been studied in the context of
      magnetic fixation of an external device to the body's surface. Excessive
      attractive force between the implant and the external device may compromise local
      circulation due to mechanical compression, leading to necrosis. OBJECTIVE: To
      evaluate the feasibility of transcutaneous magnetic fixation and assess secondary
      skin changes when subjected to a continuous static magnetic field. METHODS: Using
      the pig as an animal model, 72 implants were introduced in 12 animals. After
      wound healing, ultrasonography was performed to measure implant depths. Computer
      simulations were applied to allow magnetic attachment between implants and
      external devices without impairing local blood flow. External devices of
      different magnetic strengths were applied over the skin for 7 days. Local skin
      was examined and collected for analysis. A senior dermatopathologist blindly
      examined skin specimens and controls for abnormal findings, measuring dermal and
      epidermal thickness. Statistical analysis (P <0.05) was performed over the data.
      RESULTS: Nineteen implants presented extrusion. The remaining 53 skin sites
      underwent magnetic compression, of which 43 (81%) evolved uneventfully. Implant
      depth varied between 4.6 mm and 8.3 mm (5.8 mm; +/- 8.6 mm) with estimated
      pressure levels between 13.28 mmHg and 37.04 mmHg (27.6 mmHg; +/-6.0 mmHg).
      Stronger magnets were associated with an increase in dermal thickness (P = 0.011)
      and neovascularization (P = 0.045). CONCLUSIONS: Transcutaneous magnetic fixation
      is compatible with skin viability in vivo, under experimental conditions. Skin
      interposition between two permanent magnets resulted in a continuous static
      magnetic field stimulation, which showed similar effects to pulsed
      electromagnetic fields reported on scientific literature.

PMID- 29180177
TI  - Cutting electrocautery versus scalpel for surgical incisions: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Although cutting electrocautery can be superior to the scalpel in
      reducing blood loss and incisional time, several reports associated
      electrocautery with higher rates of wound infection, impaired healing, and worse
      cosmesis. We performed this systematic review and meta-analysis to compare
      cutting electrocautery versus scalpel for surgical incisions. MATERIALS AND
      METHODS: We conducted a computerized literature search of five electronic
      databases and included all published original studies comparing cutting
      electrocautery and scalpel surgical incisions. Relevant data were extracted from
      eligible studies and pooled as odds ratios (ORs) or standardized mean difference
      (SMD) values in a meta-analysis model, using RevMan and Comprehensive Meta
      analysis software. RESULTS: Forty-one studies (36 randomized trials, four
      observational, and one quasirandom study) were included in the pooled analysis
      (6422 participants). Compared with the scalpel incision, cutting electrocautery
      resulted in significantly less blood loss (SMD = -1.16, 95% CI [-1.60 to -0.72]),
      shorter incisional (SMD = -0.63, 95% CI [-0.96 to -0.29]) and operative times
      (SMD = -0.59, 95% CI [-1.12 to -0.05]), and lower pain scores (SMD = -0.91, 95%
      CI [-1.27 to -0.55]) with no significant differences in terms of wound infection
      rates (OR = 0.92, 95% CI [0.74-1.15]) or overall subjective scar score (SMD = 
      0.49, 95% CI [-1.72 to 0.75]). CONCLUSIONS: Surgical incision using
      electrocautery can be quicker with less blood loss and postoperative pain scores
      than the scalpel incision. No statistically significant difference was found
      between both techniques in terms of postoperative wound complications, hospital
      stay duration, and wound cosmetic characteristics. Therefore, we recommend
      routine use of cutting electrocautery for surgical incisions.

PMID- 29180178
TI  - Telemedicine broadening access to care for complex cases.
AB  - BACKGROUND: Surgical and nonsurgical specialists are highly centralized, making
      access to high-quality care difficult for many Americans. We explored the
      feasibility, benefits, preliminary outcomes, and patient satisfaction with a new
      type of health visit, in which a surgical oncologist used video telecommunication
      to manage and treat complex cancer diseases, including patients with severe
      comorbidities. MATERIALS AND METHODS: Patients visited local VA medical centers
      throughout Florida to engage in video telecommunication visits with a centralized
      surgical oncologist in Miami, who directed their oncology treatment. The average
      length of stay and rate of unplanned readmission were calculated within each
      organ. The total mileage saved was calculated by subtracting the distance between
      the patient's home address and the local VA from the distance between the
      patient's home address and the Miami VA. Travel costs were determined by the VA's
      reimbursement of $0.415/mile for health-related travel and reimbursement of
      $150.00 for an overnight hotel stay. A Likert scale with both positively and
      negatively keyed questions was used to assess patient satisfaction. RESULTS: In
      24 mo, seven unplanned readmissions occurred among 195 operations. Patients
      experienced an 80.7% reduction in travel distance and saved a total of 213,007.58
      miles by visiting their local VA instead of the Miami VA. Survey results indicate
      that 86% of patients believed that the telemedicine program made medical care
      more accessible. CONCLUSIONS: The Specialist-Directed Telemedicine Model can save
      patients substantial time and money by not traveling to centralized areas, while
      delivering greater continuity of care and patient satisfaction.

PMID- 29180179
TI  - Preoperative thrombelastography maximum amplitude predicts massive transfusion in
      liver transplantation.
AB  - BACKGROUND: Massive transfusion (MT) is frequently required during liver
      transplantation. Risk stratification of transplant patients at risk for MT is an
      appealing concept but remains poorly developed. Thrombelastography (TEG) has
      recently been shown to reduce mortality when used for trauma resuscitation. We
      hypothesize that preoperative TEG can be used to risk stratify patients for MT.
      MATERIAL AND METHODS: Liver transplant patients had blood drawn before surgical
      incision and assayed via TEG. Preoperative TEG measurements were collected in
      addition to standard laboratory coagulation tests. TEG variables including R-time
      (reaction time), angle, maximum amplitude (MA), and LY30 (clot lysis 30 min after
      MA) were correlated to red blood cell units, plasma (fresh frozen plasma),
      cryoprecipitate, and platelets during the first 24 h after surgery and tested for
      their performance using a receiver-operating characteristic curve. RESULTS:
      Twenty-eight patients were included in the analysis with a median Model for End
      Stage Liver Disease score of 17; 36% received a MT. The TEG variables associated
      with MT (defined as >=10 red blood cell units/24 h) were a low MA (P < 0.001) and
      low angle (P = 0.014). A high international normalized ratio of prothrombin time
      (P = 0.003) and low platelet count (P = 0.007) were also associated with MT. MA
      had the highest area under the curve (0.861) followed by international normalized
      ratio of prothrombin time (0.803). An MA of less than 47 mm has a sensitivity of
      90% and specificity of 72% to predict a MT. MA was the only coagulation variable
      that correlated strongly to all blood products transfused. CONCLUSIONS: TEG MA
      has a high predictability of MT during liver transplantation. The use of TEG
      preoperatively may help guide more cost effective blood bank preparation for this
      procedure as only a third of patients required a MT.

PMID- 29180180
TI  - Primary repair for pediatric colonic injury: Are there differences among adult
      and pediatric trauma centers?
AB  - BACKGROUND: Management of colonic injuries (colostomy [CO] versus primary
      anastomosis [PA]) among pediatric patients remains controversial. The aim of this
      study was to assess outcomes in pediatric trauma patient with colonic injury
      undergoing operative intervention. METHODS: The National Trauma Data Bank (2011
      2012) was queried including patients with isolated colonic injury undergoing
      exploratory laparotomy with PA or CO with age <=18 y. Missing value analysis was
      performed. Patients were stratified into two groups: PA and CO. Outcome measures
      were mortality, in-hospital complications, and hospital length of stay.
      Multivariate regression analysis was performed. RESULTS: A total of 1151 patients
      included. Mean +/- standard deviation age was 11.61 +/- 2.8 y, and median [IQR]
      Injury Severity Score was 12 [8-16]; 39% (n = 449) of the patients had CO, and
      35.6% (n = 410) were managed in pediatric trauma centers (PC). Patients with CO
      had a higher Injury Severity Score (P < 0.001), a trend toward lower blood
      pressure (P = 0.40), and an older age (P < 0.001). There was no difference in
      mortality between the PA and CO groups. However, patients who underwent PA had a
      shorter length of stay (P < 0.001) and lower in-hospital complications (P <
      0.001). A subanalysis shows that, after controlling for all confounding factors,
      patients managed in PC were 1.2 times (1.2 [1.1-2.1], P = 0.04) more likely to
      receive a CO than those patients managed in adult trauma centers (AC). Moreover,
      there was no difference in mortality between the AC and the PC (P = 0.79).
      CONCLUSIONS: Our data demonstrate no difference in mortality in pediatric trauma
      patients with colonic injury who undergo primary repair or CO. However, adult
      trauma centers had lower rates of CO performed as compared to a similar cohort of
      patients managed in pediatric trauma centers. Further assessment of the reasons
      underlying such differences will help improve patient outcomes.

PMID- 29180181
TI  - Marked stem/progenitor cell expansion occurs early after murine ileostomy: a new
      model.
AB  - BACKGROUND: Improving treatment for short bowel syndrome requires a better
      understanding of how intestinal adaptation is affected by factors like
      mechanoluminal stimulation. We hypothesized that in mice, luminal diversion via
      an ileostomy would drive adaptive changes similar to those seen in human
      intestine after diversion while offering the opportunity to study the immediate
      events after resection that precede intestinal adaptation. MATERIALS AND METHODS:
      With Institutional Animal Care and Use Committee approval, a distal ileostomy
      with a long distal Hartman's was created in 9- to 14-week-old C57/B6 mice (n =
      8). Control mice only had a midline laparotomy without stoma formation (n = 5). A
      rim of tissue from the proximal stoma was resected as a historical control for
      the proximal segment. Postoperatively, mice received a high-protein liquid diet
      and water ad libitum. On day 3, tissue from both the proximal and distal limbs
      were collected for histologic and RNA analysis. Morphometric measures,
      immunofluorescent antigen detection, and RNA expression were compared with
      Student paired t-tests with a P value < 0.05 considered significant. RESULTS: At
      3 d, survival for mice with an ileostomy was 87% and average weight loss was
      12.5% of initial weight compared to 6.05% for control mice. Compared to the
      distal limb, the proximal limb in mice with an ileostomy demonstrated
      significantly taller villi with deeper and wider crypts. The proximal limb also
      had decreased expression of intestinal stem cell markers lgr5, bmi1, sox9, and
      ascl2. Fewer goblet and enteroendocrine cells per hemivillus were also noted in
      the proximal limb. In control mice, none of these measures were significant
      between proximal and distal ileum except for villus height. CONCLUSIONS: This new
      murine ileostomy model allows study of intestinal adaptation without intestinal
      anastomosis, which can be technically challenging and morbid.

PMID- 29180182
TI  - Perioperative warming, oxygen, and Ilomedin on oxygenation and healing in
      infrainguinal bypass surgery.
AB  - BACKGROUND: Perioperative adjuncts are utilized across surgical specialities with
      the goal of improving patient outcomes. High-dose oxygen and extended warming are
      shown to increase wound collagen deposition during abdominal surgery.
      Prostacyclin is shown to improve limb salvage and patency rate in infrainguinal
      bypass (IIB) surgery. This study evaluated the impact of these adjuncts on
      healing and perfusion post IIB surgery. METHODS: This randomized controlled study
      allocated patients undergoing IIB surgery into three treatment arms
      (perioperative high-dose oxygen, extended warming, and a synthetic prostacyclin)
      or a control group. The primary outcome was accumulation of hydroxyproline (OHP,
      collagen surrogate marker) as collected in polytetrafluoroethylene implants on
      day 5. Secondary outcomes included levels of growth factors and cytokines, and
      tissue oxygenation of the wound and foot as measured by hyperspectral technology
      and ankle-brachial pressure index. Clinical outcomes were observed to day 30,
      with long-term follow-up of 12 mo. RESULTS: Seventy-one patients completed the
      study. Comparing treatment groups with the control at day 5, there were no
      differences in OHP, growth factors or cytokines levels, or improvement in tissue
      oxygenation at the surgical incision. However, there was more flow to the foot
      (HT-SUM (%) change) in the Ilomedin group compared to control (0% versus -14.6%,
      P = 0.045). HT-deoxy was higher at the peripheries in the oxygen and temperature
      groups, suggesting decreased tissue oxygenation. CONCLUSIONS: The perioperative
      treatments did not dramatically improve oxygenation or healing of the surgical
      wound in IIB surgery; however, Ilomedin may result in greater flow to the
      peripheries.

PMID- 29180183
TI  - Timing of valproic acid in acute lung injury: prevention is the best therapy?
AB  - BACKGROUND: Acute lung injury and respiratory distress syndrome is characterized
      by uncontrolled inflammation of the lungs after a severe inflammatory stimulus.
      We have previously demonstrated an ameliorated syndrome and improved survival in
      mice with early administration of valproic acid (VPA), a broad-spectrum histone
      deacetylase inhibitor, while studies in humans have shown no benefit when anti
      inflammatories are administered late. The current study tested the hypothesis
      that early treatment would improve outcomes in our gram-negative pneumonia
      induced acute lung injury. MATERIALS AND METHODS: Mice (C57BL/6) had 50 * 106
      Escherichia coli (strain 19,138) instilled endotracheally and VPA (250 mg/kg)
      administered intraperitoneally 3, 4, 6, and 9 h (n = 12/group) later. Six hours
      after VPA administration, the animals were sacrificed, and bronchoalveolar lavage
      (BAL) fluid interleukin-6 (IL-6), tumor necrosis factor, neutrophils and
      macrophages as well as the E coli colony-forming units were quantified. Plasma IL
      6 was also measured. A separate group of mice (n = 12/group) were followed
      prospectively for 7 days to assess survival. RESULTS: BAL IL-6 and tumor necrosis
      factor as well as plasma IL-6 were significantly lower in the animals
      administered VPA within 3 h (P < 0.05) but not when administered later (4, 6, 9
      h). There was no difference in the BAL E coli colony-forming units, macrophage,
      or neutrophil numbers at any time point. Survival improved only when VPA was
      administered within 3 h. CONCLUSIONS: A narrow therapeutic window exists in this
      murine model of gram-negative pneumonia-induced acute lung injury and likely
      explains the lack of response in studies with late administration of anti
      inflammatory therapies in clinical studies.

PMID- 29180184
TI  - Status of trauma quality improvement programs in the Americas: a survey of trauma
      care providers.
AB  - INTRODUCTION: Global disparities in trauma care contribute to significant
      morbidity and mortality (M&M) in low- and middle-income countries. Implementation
      of quality improvement (QI) programs has been shown to be a cost-effective
      strategy to improve trauma care quality. In this study, we aim to characterize
      the trauma QI programs in a broad range of low- to high-income countries in the
      Americas to assess areas for targeted improvement in global trauma QI efforts.
      METHODS: We conducted a mixed methods survey of trauma care providers in North
      and South America distributed in-person at trauma care conferences and online via
      a secure survey platform. Responses were analyzed to observe differences across
      respondent country income categories. RESULTS: One hundred ninety-two surveys
      were collected, representing 21 different countries from three income strata
      (three lower-middle-, eleven upper-middle-, and eight high-income countries).
      Respondents were primarily physicians or physicians-in-training (85%). Eighty
      nine percent of respondents worked at an institution where M&M conferences
      occurred. M&M conferences were significantly more frequent at higher income
      levels (P = 0.002), as was attending physician presence at M&M conferences (70%
      in high-income countries versus 43% in lower-middle-income countries). There were
      also significant differences in the structure, quality, and follow-up of M&M
      conferences in lower versus higher income countries. Sixty-three percent of
      respondents reported observing some kind of positive change at their institution
      due to M&M conferences. The survey also suggested significantly higher
      utilization of autopsy (P < 0.001) and electronic trauma registries (P = 0.01) at
      higher income levels. CONCLUSIONS: This survey demonstrated an encouraging
      pattern of widespread adoption of trauma QI programs in several countries in
      North and South America. However, there continue to be significant disparities in
      the structure and function of trauma QI efforts in low- and middle-income
      countries in the Americas. There are several potential areas for development and
      improvement of trauma care systems, including standardization of case selection
      and follow-up for M&M conferences and increased use of medical literature to
      improve evidence-based care.

PMID- 29180185
TI  - ADAM-17 expression is enhanced by FoxM1 and is a poor prognostic sign in gastric
      carcinoma.
AB  - BACKGROUND: The ADAMs proteases are a multifunctional family of proteins, many of
      which participate in the pathogenesis of cancers. The expression and regulation
      of ADAMs has not yet been fully examined in gastric cancer. MATERIALS AND
      METHODS: Using reverse transcription-PCR, messenger RNA expression of ADAM-9,
      ADAM-10, ADAM-11, ADAM-12, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 was detected in
      gastric cancer. ADAM-10, ADAM-17, ADAM-28, and FoxM1 expression in gastric cancer
      was detected by Western blot and immunohistochemistry. The correlation between
      ADAM-17 and FoxM1 was analyzed in vivo and in vitro. RESULTS: The messenger RNA
      levels of ADAM-9, ADAM-10, ADAM-15, ADAM-17, ADAM-28, and ADAM-33 were increased
      in tumor tissues compared with adjacent normal tissue, especially ADAM-10, ADAM
      17, and ADAM-28. FoxM1 expression correlated significantly with ADAM-17
      expression. FoxM1 regulates ADAM-17 expression in vivo and in vitro, which in
      turn influences proliferation and tumor growth of gastric cancer cells.
      Furthermore, Cox regression analysis revealed that FoxM1 and ADAM-17 are
      independent prognostic factors for patients with gastric cancer. CONCLUSIONS:
      These results indicate that overexpression of ADAMs may contribute to gastric
      cancer progression and that ADAM-17 is a downstream target of FoxM1. Overall, the
      present study highlights the potential for FoxM1 and ADAMs as potential
      therapeutic targets for patients with gastric carcinoma.

PMID- 29180186
TI  - Laparoscopic versus open liver resection for colorectal liver metastases: a
      systematic review.
AB  - BACKGROUND: Laparoscopic liver resection (LLR) has been proposed as a safe and
      feasible treatment option for colorectal liver metastasis (CRLM). However, the
      short-term and oncologic outcomes of LLR versus open liver resection (OLR) for
      CRLM have not been adequately assessed. Thus, we herein provide an updated
      systematic review comparing short-term and oncologic outcomes of CRLM patients
      undergoing LLR versus OLR. METHODS: A systematic literature search was performed
      in the Pubmed, Embase, and Cochrane Library databases (until November 2, 2016)
      with a limitation to the publications in English. Quality assessment was
      performed based on the modification of the Newcastle-Ottawa Scale. Dichotomous
      data were calculated by odds ratio (OR), and continuous data were calculated by
      weighted mean difference (WMD) with 95% confidence intervals (CIs). RESULTS: A
      total of 28 studies enrolling 4591 patients with CRLM were included. With respect
      to short-term outcomes, patients in LLR group showed significantly reduced blood
      loss (WMD: -143.64; 95% CI: -180.56 to -106.73; I2 = 86%; P < 0.001), lower
      operative transfusion requirement (OR: 0.40; 95% CI: 0.30-0.53; I2 = 0%; P <
      0.001), shorter hospital stay (WMD: -2.47; 95% CI: -2.99 to -1.94; I2 = 82%; P <
      0.001), reduced overall postoperative morbidity (OR: 0.53; 95% CI: 0.42-0.66; I2
      = 38%; P < 0.001) and reduced severe morbidity (OR: 0.44; 95% CI: 0.32-0.60; I2 =
      35%; P < 0.001). Regarding oncologic outcomes, there were no significant
      differences between the two surgical procedures in recurrence and 1-, 3-, and 5
      overall survival and disease-free survival except for slightly higher R0
      resection rate in LLR group was slightly higher than that of OLR group (OR: 1.43;
      95% CI: 1.03-1.97; I2 = 37%; P = 0.03). CONCLUSIONS: LLR should be the standard
      approach for selected patients with CRLM, and further research should focus on
      determining which patients would benefit most from LLR.

PMID- 29180187
TI  - Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting
      expression of heat shock protein 90.
AB  - BACKGROUND: Myocardial cell injury and cardiac myocyte apoptosis are associated
      with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury.
      The aim of this study was to explore the role of Gln on cardiac myocytes in a
      cecal ligation and puncture (CLP) model of sepsis in Wistar rats. MATERIALS AND
      METHODS: Following induction of sepsis in a CLP rat model, viral encoding heat
      shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and
      knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically,
      and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end
      labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated
      X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by
      western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8,
      and caspase-9 were detected by enzyme-linked immunosorbent assay. RESULTS: Rat
      cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90
      overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2
      expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of
      apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly
      upregulated in the CLP model, which were reduced by Gln treatment and Hsp90
      overexpression. CONCLUSIONS: Gln reduced apoptosis of cardiac myocytes in a rat
      model of sepsis, by promoting Hsp90 expression. Further studies are needed to
      determine the possible therapeutic action of Gln in sepsis in human tissue.

PMID- 29180188
TI  - Statewide assessment of surgical outcomes and the acute care surgery model.
AB  - BACKGROUND: The acute care surgery (ACS) model has been widely implemented with
      single institution studies demonstrating improved outcomes. Recent multicenter
      studies have raised questions about the economics and efficacy of ACS. This study
      compares traditional and ACS outcomes across an entire state. METHODS: A
      retrospective review of Virginia's Health Information administrative database was
      completed. Adults admitted with appendicitis or cholecystitis between 2008 and
      2014 were included. Hospital administration was contacted to determine surgical
      model. To compare patient characteristics, t-test and chi-square analyses were
      used. Total charges and length of stay (LOS) differences between ACS and
      traditional were examined using generalized linear models, whereas logistic
      regression was used for the presence of complications and 30-day mortality.
      RESULTS: Overall, the ACS model showed an increased proportion of uninsured
      patients with a higher rate of comorbidities. In the appendicitis subgroup, (n =
      22,011; ACS n = 1993), ACS patients had higher total charges ($30,060 versus
      $28,460, P = 0.013), longer LOS (3.31 versus 2.92 d, P < 0.001), and higher
      chance of complications (odds ratio [OR] = 1.2, P = 0.016) and mortality (OR =
      2.4, P = 0.029). After adjustment for comorbidities and insurance, mortality was
      no longer significantly different. In the cholecystitis group (n = 6936; ACS n =
      777), ACS patients had a longer LOS (4.55 versus 4.13 d; P = 0.009) without
      significant differences in mortality, complications, or cost. There were no
      significant differences after adjustment for patient characteristics.
      CONCLUSIONS: ACS patients in Virginia have a higher rate of medical comorbidities
      and uninsured status, with slightly worse outcomes than the traditional model for
      appendicitis. Further studies to determine which patients benefit the most from
      ACS are warranted.

PMID- 29180189
TI  - Impact of triage guidelines on prehospital triage: comparison of guidelines with
      a statistical model.
AB  - BACKGROUND: The American College of Surgeons developed the National Field Triage
      Decision Scheme (NFTDS) that has been adapted by many trauma centers in the
      nation, but quantitative evidence of its efficacy is unclear. We compare the
      NFTDS and state of Ohio guidelines to the "observed" rates and with rates derived
      using a statistical model. METHODS: We used 4757 trauma records from 2008-2012
      available from the state and calculated undertriage (UT) and overtriage (OT)
      rates. We then simulated the NFTDS and the state guidelines for those years and
      estimated the corresponding UT and OT rates. We finally compared these rates with
      those derived from a multivariate logistic regression model. RESULTS: For the
      state data, both NFTDS and state guidelines produced lower UT rate (~9%) compared
      with the observed rate (~17%), whereas the OT rates were higher (>85%) than the
      observed rates (~54%). The statistical model identified novel factors that were
      not directly available in the NFTDS; change in responsiveness (odds ratio [OR] =
      1.924) and complaint in body (OR = 3.140), back (OR = 1.890), chest (OR = 3.191),
      head (OR = 3.878), and abdomen (OR = 2.966). Although the statistical model
      performed similar to observed rates, it performed considerably better than NFTDS
      (UT = 1.93% versus 9.03%; OT = 66.42% versus 87.52%) and state guidelines (UT =
      2.18% versus 8.72%; OT = 64.09% versus 86.52%). CONCLUSIONS: The current NFTDS
      and state's triage guidelines do not appear to achieve the ACS recommendation of
      <5% UT and <35% OT rates in the state of Ohio. Inclusion of region-specific
      factors may help enhance the current NFTDS guidelines and aid in the first
      impression or judgment of the Emergency Medical Services personnel to improve
      trauma care and reduce cost.

PMID- 29180190
TI  - Patterns of sural nerve innervation of the sural artery with implication for
      reconstructive surgery.
AB  - BACKGROUND: Most of the literature concerning the neurocutaneous flap is related
      to its anatomic investigation and clinical application, and the more in-depth
      physiological problem such as whether the cutaneous nerve contains sympathetic
      fibers that innervate its accompanying vessels has never been explored. MATERIALS
      AND METHODS: Dissection was first performed on three rabbits. In another 22
      rabbits, two rabbits undergoing no surgery were used as the normal control group.
      In the remaining 20 rabbits, the 40 sides of hind limbs were divided into a nerve
      severance group, where the sural nerve was transected at its origin after
      creation of the proximally based sural neurocutaneous flap, and a nerve
      preservation group, in which the continuation of the sural nerve was preserved.
      The sural neurovascular bundles at four time points were harvested for
      immunohistochemical and Western blotting analyses of the expression of tyrosine
      hydroxylase (TH). An infrared thermal imager was used for measurement of the
      average flap temperature within the first 24 h. RESULTS: The sural neurovascular
      bundle entered the skin at 4.5 +/- 1.2 cm above the lateral malleolus. The TH in
      the sural nerve and tunica adventitia of the sural artery showed a synchronized
      abated expression in the nerve severance group. The TH expression showed no
      decline in the nerve preservation group. The average flap temperature in the
      nerve severance group was higher than that in the nerve preservation group
      starting from 2 h after flap harvest (P = 0.05). CONCLUSIONS: The cutaneous nerve
      has meted out sympathetic fibers to the accompanying artery, regulating its
      vascular tone.

PMID- 29180191
TI  - Suture thread check test for detection of surgical site contamination: a
      prospective study.
AB  - BACKGROUND: Surgical site infection (SSI) is a common complication of surgical
      procedures. AIM: Our study aimed at investigating a new method based on
      assessment of suture thread colonization to identify patients developing an SSI.
      MATERIALS AND METHODS: We prospectively enrolled 119 patients undergoing elective
      surgery. For each patient, a synthetic absorbable thread in Lactomer 9-1
      (Polisorb Gauge 2) inserted in the surgical site at the end of surgery was sent
      to the microbiology laboratory after 48 h to assess colonization of its inner
      tract. RESULTS: Forty (33.6% of cases) patients had a colonized thread.
      Antibiotic prophylaxis was administered to 66 of 79 patients who did not display
      a colonized thread and to 20 of the 40 patients with a colonized thread (83.5%
      versus 50%, respectively, P = 0.0002). An SSI was observed only in patients with
      a colonized thread (10% versus 0, P = 0.02). The microorganisms identified in
      colonized threads were the same identified in SSIs. CONCLUSIONS: Since an SSI was
      found only in patients with colonized threads, the method described here may be
      valuable for identifying patients developing an SSI. Moreover, the method can
      also be useful for targeting efficient antibiotic therapy to the culprit
      microorganisms.

PMID- 29180192
TI  - Reduced serum cholinesterase activity indicates splenic modulation of the sterile
      inflammation.
AB  - BACKGROUND: Sterile inflammation is an immediate and well-coordinated immune
      response to surgical injury. The cholinergic system plays a pivotal role in the
      inflammatory response. Induced inflammation stimulates the vagus nerve, which in
      turn activates anti-inflammatory nonneuronal processes. Serum cholinesterase
      (butyrylcholinesterase [BChE]) is an enzyme that hydrolyzes acetylcholine.
      Measuring the activity of the BChE in blood might indicate the level of the
      nonneuronal cholinergic activity. The spleen is a major organ of the immune
      system playing an important role during inflammation. A functional connection of
      the neuroimmune reflex has thus far been described only in experimental settings.
      MATERIALS AND METHODS: In 48 patients receiving major pancreatic surgery, BChE
      activity was measured by applying point-of-care-testing, in addition to standard
      laboratory tests. RESULTS: The BChE activity decreased in patients receiving
      surgery. This reduction emerged much earlier than changes in C-reactive protein
      concentration, an inflammatory biomarker broadly used in the clinical
      environment. A milder reduction in the BChE activity was observed in patients
      subjected to surgery with splenectomy than in those with a preserved spleen.
      CONCLUSIONS: The use of the point-of-care-testing system for quick bedside
      diagnostics and the rapid effects of inflammation on BChE levels provide a method
      and a marker to facilitate the early detection of systemic inflammation.
      Furthermore, this study provides evidence that the experimentally documented
      neuroimmune interaction is part of the physiological response to surgery-induced
      sterile inflammation. Splenic function plays an essential role in modulating the
      cholinergic anti-inflammatory response.

PMID- 29180193
TI  - Defining payments associated with the treatment of colorectal cancer.
AB  - BACKGROUND: While bundled payments aim to reduce variations in health care
      spending across the continuum of care, data reporting on variations in payments
      for privately insured patients undergoing treatment for colon cancer (CC) are
      lacking. The current study sought to characterize variations in payments received
      for the treatment of CC using a cohort of commercially insured patients. METHODS:
      Patients who underwent a colectomy for CC were identified using the MarketScan
      Database for 2010-2014. Multivariable regression analysis was used to calculate
      and compare risk-adjusted payments between patients. RESULTS: A total of 18,337
      patients were identified who met inclusion criteria. The median risk-adjusted
      payment for surgery was $26,408 (IQR: $19,193-$38,037) ranging from $19,762 (IQR:
      $15,595-$25,636) among patients in the lowest quartile of payments to $33,809
      (IQR: $24,783-$48,254) for patients in the highest (+?71.1%). The median risk
      adjusted payment for chemotherapy was $70,090 (IQR: $57,813-$83,216); compared
      with patients in the lowest quartile of payments, payments associated with
      chemotherapy were 40.4% higher among patients in the highest quartile of payments
      (Q1 versus Q4: $56,827 [IQR: 49,173-65,353] versus $79,801 [IQR: 67,270-90,999]).
      When stratified by treatment type, patients in the highest two quartiles of risk
      adjusted payments accounted for a total of 58.5% of all payments, whereas
      patients in the lower two quartiles of risk-adjusted payments accounted for only
      41.5% of all payments. A younger patient age, increasing patient comorbidity and
      undergoing an open operation were associated with higher overall payments.
      CONCLUSIONS: Wide variations in payments exist for the treatment for colon
      cancer. Episode-based bundle payments for surgery and chemotherapy may
      differentially impact reimbursement for CC.

PMID- 29180194
TI  - Perioperative complications of emergent and elective procedures in psychiatric
      patients.
AB  - BACKGROUND: Patients with psychiatric disorders have an increased risk for
      morbidity and mortality from other medical conditions. METHODS: Medical records
      of all the patients undergoing appendectomy (n = 2594) and laparoscopic
      cholecystectomy (n = 2874) from 2009 to 2014 in one hospital were reviewed. For
      each patient with a documented psychiatric disorder undergoing surgery, four
      controls were matched. RESULTS: The final sample of patients undergoing
      appendectomy included 96 patients, whereas those undergoing laparoscopic
      cholecystectomy included 260 patients. In the emergent scenario, psychiatric
      patients had longer time from symptom appearance to admission, longer
      hospitalization duration, and increased rate and severity of postoperative
      complications. In the elective scenario, psychiatric patients were shown to have
      more postoperative respiratory complications. CONCLUSIONS: Our results, together
      with the high prevalence of psychiatric disorders in the population, underscore
      the importance of screening for psychiatric disorders and their proper
      documentation in surgical patients.

PMID- 29180195
TI  - Sutures versus new cyanoacrylates in prosthetic abdominal wall repair: a
      preclinical long-term study.
AB  - BACKGROUND: As an alternative to sutures, meshes used for hernia repair can be
      fixed using cyanoacrylate-based adhesives. Attempts to improve these adhesives
      include alkyl-chain lengthening to reduce their toxicity. This preclinical study
      compares the long-term behavior of cyanoacrylates of different chain lengths
      already used in hernia repair and new ones for this application. MATERIALS AND
      METHODS: Partial abdominal wall defects were repaired using a Surgipro mesh in 18
      New Zealand White rabbits, and groups were established according to the mesh
      fixation method: sutures (control), Glubran 2 (n-butyl), Ifabond (n-hexyl), and
      the new adhesives SafetySeal (n-butyl), and Evobond (n-octyl). Six months after
      surgery, recovered implants were examined to assess adhesive degradation, host
      tissue reaction, and biomechanical strength. RESULTS: All the cyanoacrylate
      groups showed good host tissue incorporation in the meshes. Macrophage responses
      to Glubran and Ifabond were quantitatively greater compared with sutures. Cell
      damage caused by the adhesives was similar, and only Glubran induced
      significantly more damage than sutures. Significantly lower collagen 1/3
      messenger RNA expression was induced by Ifabond than the remaining fixation
      materials. No differences were observed in collagen expression except slightly
      reduced collagen I deposition in Glubran/Ifabond and collagen III deposition in
      the suture group. Mechanical strengths failed to vary between the suture and
      cyanoacrylate groups. CONCLUSIONS: All cyanoacrylates showed good long-term
      behavior and tolerance irrespective of their long or intermediate chain length.
      Cyanoacrylate residues persisted at 6 mo, indicating their incomplete
      degradation. Biomechanical strengths were similar both for the adhesives and
      sutures.

PMID- 29180196
TI  - Laparotomy causes loss of peritoneal mesothelium prevented by humidified CO2
      insufflation in rats.
AB  - INTRODUCTION: Avoiding tissue desiccation is a common recommendation to reduce
      postoperative complications following open abdominal surgery, although difficult
      to achieve delicately without damaging the peritoneal mesothelium. Insufflation
      of humidified-warm CO2 into the abdomen during open abdominal surgery is proposed
      as an invisible, effortless way to prevent desiccation. We hypothesized that
      desiccation during open abdominal surgery would cause loss of peritoneal
      mesothelium that would be prevented by insufflation of humidified-warm CO2.
      METHODS: Nine Wistar rats were assigned to 1 h of anesthesia only, laparotomy
      only, or laparotomy with insufflation of humidified-warm CO2. Twelve hours after
      treatment, rats were euthanized and tissue samples were excised. Scanning
      electron microscopy (SEM) and light microscopy (LM) images of visceral and
      parietal peritoneum were scored by two independent, blinded examiners for loss of
      mesothelium and other indications of inflammation, including measurement of
      apoptosis by detection of DNA cleavage. RESULTS: Loss of peritoneal mesothelium
      was found in peritoneum exposed to laparotomy only (SEM: P = 0.002; LM: P =
      0.01), and mesothelial loss was reduced by humidified-warm CO2 (SEM: P < 0.001;
      LM P = 0.004). Similarly, DNA cleavage was significantly higher on the peritoneal
      surface following laparotomy only, compared with anesthesia only (P = 0.0055) and
      laparotomy with humidified-warm CO2 insufflation (P = 0.0003). CONCLUSIONS: In a
      rat model, exposing the peritoneal mesothelial to conditions that replicate
      minimum recommended air flow within an operating room causes inadvertent loss of
      mesothelium and signs of inflammation that can be prevented by insufflating
      humidified-warm CO2 into the open abdominal cavity.

PMID- 29180197
TI  - TSG-6 is highly expressed in human abdominal aortic aneurysms.
AB  - BACKGROUND: The formation of abdominal aortic aneurysms (AAA) is characterized by
      a dominance of proinflammatory forces that result in smooth muscle cell
      apoptosis, extracellular matrix degradation, and progressive diameter expansion.
      Additional defects in the antiinflammatory response may also play a role but have
      yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent
      antiinflammatory protein involved in extracellular matrix stabilization and cell
      migration active in many pathological conditions. Here, we describe its role in
      AAA formation. METHODS: Blood and/or aortic tissue samples were collected from
      organ donors, subjects undergoing elective AAA screening, and open surgical AAA
      repair. Aortic specimens collected were preserved for IHC or immediately assayed
      after tissue homogenization. Protein concentrations in tissue and plasma were
      assayed by ELISA. All immune cell populations were assayed using FACS. In vitro,
      macrophage polarization from monocytes was performed with young, healthy donor
      PBMCs. RESULTS: TSG-6 was found to be abnormally elevated in both the plasma and
      aortic wall of patients with AAA compared with healthy and risk-factor matched
      non-AAA donors. We observed the highest tissue concentration of TSG-6 in the less
      diseased proximal and distal shoulders compared with the central aspect of the
      aneurysm. IHC localized most TSG-6 to the tunica media with minor expression in
      the tunica adventitia of the aortic wall. Higher concentrations of both M1 and M2
      macrophages where also observed, however M1/M2 ratios were unchanged from healthy
      controls. We observed no difference in M1/M2 ratios in the peripheral blood of
      risk-factor matched non-AAA and AAA patients. Interesting, TSG-6 inhibited the
      polarization of the antiinflammatory M2 phenotype in vitro. CONCLUSIONS: AAA
      formation results from an imbalance of inflammatory forces causing aortic wall
      infiltration of mononuclear cells leading to the vessel breakdown. In the AAA
      condition, we report an elevation of TSG-6 expression in both the aortic wall and
      the peripheral circulation.

PMID- 29180198
TI  - Surgical tray optimization as a simple means to decrease perioperative costs.
AB  - BACKGROUND: Health care spending in the US remains excessively high. Aside from
      complicated, large-scale efforts at health care cost reduction, there are still
      relatively simple ways in which individual hospitals can cut unnecessary costs
      from everyday operations. Inspired by recent publications, our group sought to
      decrease the costs associated with surgical instrument processing at a large,
      multihospital academic center. METHODS: This was a single-site observational
      study conducted at a large academic medical center. At the study start, all
      attending surgeons within the section of pediatric surgery agreed to standardize
      the pediatric surgery trays and to eliminate instruments that were deemed
      unnecessary from each tray. A multidisciplinary start-up meeting was held, and
      this meeting included stakeholders from central sterile processing, operating
      room nursing, scrub technicians, and materials management along with all five
      pediatric surgeons. Each tray was addressed individually. Instruments were
      eliminated from trays only if there was unanimous agreement among all the
      surgeons in the group. If no instruments in a given surgical tray were deemed
      necessary, the entire tray was eliminated from sterile processing rotation.
      Feedback questionnaires were drafted by the multidisciplinary team that
      participated in the start-up meeting. Surgeons were allowed to request for
      certain instruments to be placed back into the trays at any time, and the
      questionnaires also allowed for free-hand comments. Surgical kit preparation time
      was obtained from the institutional barcode scanning system. The cost per second
      of sterile processing labor was calculated using regional median salary for
      sterile processing technicians in the state of Connecticut. Using the pediatric
      surgery section as the model unit, this method was then applied to pediatric
      urology, neurosurgery, spine surgery, and orthopedics. RESULTS: The pediatric
      surgery section eliminated an average of 59.5% of instruments per tray, resulting
      in an overall reduction of 1826 (39.5%) instruments from rotation, 45,856 fewer
      instruments processed per year, and nine trays eliminated completely from regular
      rotation. Processing time for six commonly used trays was reduced by an average
      of 28.7%. The urology section eliminated 18 trays from regular rotation and 179
      (10.1%) instruments in total. Pediatric orthopedics, neurosurgery, and spine
      sections eliminated 708 (17.1%), 560 (92.7%), and 31 (32.2%) instruments,
      respectively, resulting in approximately 18,804 fewer instruments processed per
      year. Among all five surgical sections, annual instrument cost avoidance after
      tray optimization was estimated at $53,193 to $531,929 using average instrument
      life spans ranging from 1-10 y. Negative feedback and requests for instrument
      replacement were both minimal on feedback questionnaires. CONCLUSIONS: Surgical
      tray optimization represents a relatively simple microsystem improvement that
      could result in significant hospital cost reduction. Although difficult to
      quantify, other gains from surgical kit optimization include decreased weight per
      tray, decreased materials cost, and decreased labor required to count,
      decontaminate, and pack surgical trays.

PMID- 29180199
TI  - Dose-dependent effect of parathyroid hormone on fracture healing and bone
      formation in mice.
AB  - BACKGROUND: Parathyroid hormone (PTH) is the only clinically approved
      osteoanabolic drug for osteoporosis treatment. However, PTH is not established
      for the treatment of fracture healing, and doses of PTH diverge significantly
      between different studies. We hypothesized that the effect of PTH on promoting
      fracture healing and bone formation is dose dependent. MATERIALS AND METHODS: In
      vivo, mice were treated with PTH (10, 40, and 200 MUg/kg) in a closed femoral
      fracture model. Fracture healing was analyzed after 4 weeks. The fourth lumbar
      vertebra was analyzed to assess systemic effects. In addition, osteoblasts from
      calvaria of mice were treated in vitro with PTH doses of 10-5-50 nM, and their
      differentiation was analyzed after 26 days. RESULTS: In vivo, PTH dose
      dependently stimulated bone formation in the fracture callus and the vertebral
      body. However, PTH treatment did not increase biomechanical stiffness of the
      fractured femora in a dose-dependent manner. The increased bone formation in the
      200 MUg/kg group was associated with a depletion of osteoclasts, indicating
      diminished bone remodeling. Of interest, in vitro, we observed diminished
      mineralization with the highest doses of PTH in osteoblast cultures. CONCLUSIONS:
      PTH dose-dependently stimulates bone formation in vivo. However, during fracture
      healing, this did not result in a dose-dependent increase of the mechanical
      stiffness of the fracture callus. Taken together, our in vivo and in vitro data
      indicate that the dose-dependent effects of PTH during fracture healing are based
      on the actions on multiple cell types, thereby influencing not only bone
      formation but also osteoclastic callus remodeling.

PMID- 29180200
TI  - Indicators of breast cancer in patients undergoing microdochectomy for a
      pathological nipple discharge in a middle-income country.
AB  - BACKGROUND: The management of a pathological nipple discharge often involves
      surgery for the exclusion of a malignant etiology. This study aimed to determine
      the prevalence of cancer in patients who had microdochectomy for pathological
      nipple discharge in a population in South Africa and to evaluate patients'
      demographics and clinical characteristics as indicators of underlying cancer and
      make recommendations for their management in resource-limited settings. MATERIALS
      AND METHODS: Clinical, radiological, and histological data from 153 patients who
      underwent a microdochectomy for a pathological nipple discharge at two South
      African breast clinics was collected. RESULTS: Invasive or in situ cancer was
      found in 12 patients (7.84%), and in all patients, cancer was associated with a
      bloody nipple discharge. Bloody discharge had a sensitivity of 100% in indicating
      cancer, specificity of 55.32%, positive predictive value of 16%, and negative
      predictive value of 100%. Patients with breast cancer were also more likely to be
      aged 55 y or older (P = 0.04). Preoperative mammogram and ultrasound were poor in
      detecting cancer (0/12). CONCLUSIONS: In our population, a bloody discharge in
      women aged 55 years or older should mandate a microdochectomy, with selective
      surgery for younger women and those with nonbloody discharges. Thorough clinical
      examination to determine the true color and nature of the discharge is vital in
      the initial assessment of these patients. Preoperative radiology is not helpful
      in determining the presence of cancer (in an isolated pathological nipple
      discharge), and microdochectomy still remains the gold standard in diagnosing
      cancer in these patients.

PMID- 29180201
TI  - Laparoscopic repair of perforated peptic ulcer: simple closure versus omentopexy.
AB  - BACKGROUND: This report presents our experience with laparoscopic repair
      performed in 118 consecutive patients diagnosed with a perforated peptic ulcer
      (PPU). We compared the surgical outcome of simple closure with modified Cellan
      Jones omentopexy and report the safety and benefit of simple closure. METHODS:
      From January 2010 to December 2014, 118 patients with PPU underwent laparoscopic
      repair with simple closure (n = 27) or omentopexy (n = 91). Charts were
      retrospectively reviewed for demographic characteristics and outcome. The data
      were compared by Fisher's exact test, Mann-Whitney U test, Pearson's chi-square
      test, and the Kruskal-Wallis test. The results were considered statistically
      significant if P < 0.05. RESULTS: No patients died, whereas three incurred
      leakage. After matching, the simple closure and omentopexy groups had similarity
      in sex, systolic blood pressure, pulse rate, respiratory rate, Boey score,
      Charlson comorbidity index, Mannheim peritonitis index, and leakage. There were
      statistically significant differences in age, length of hospital stay, perforated
      size, and operating time. Comparison of the operating time in the <=4.0 mm and
      5.0-12 mm groups revealed that the simple closure took less time than omentopexy
      in both groups (<=4.0 mm, 76 versus 133 minutes, P < 0.0001; 5.0-12 mm, 97 versus
      139.5 minutes; P = 0.006). CONCLUSIONS: Compared to the omentopexy, laparoscopic
      simple closure is a safe procedure and shortens the operating time.

PMID- 29180202
TI  - Resident and fellow participation in Thyroid and Parathyroid surgery: an ACS
      NSQIP clinical outcomes analysis.
AB  - BACKGROUND: The effect of decreased overall hours of training in surgical
      specialties is still being examined. Of particular interest is the safety of
      patients undergoing surgeries with trainee surgeons. The aim of this study was to
      identify if there were significant differences in outcomes of patients undergoing
      commonly performed thyroid and parathyroid surgeries when trainees were involved.
      MATERIALS AND METHODS: Postoperative complication rates, length of stay (LOS),
      and total operation time (OT) data were gathered from the American College of
      Surgeons National Surgical Quality Improvement Project database. The cases were
      identified by CPT code and were divided based on the training level of the
      participating resident surgeon: Junior (postgraduate year [PGY] 1-2), senior (PGY
      3-5), fellow (PGY >5), as well as an attending-only group where no resident was
      present. We compared the clinical outcomes, LOS, and OT in each trainee group to
      the attending-only group as the reference. RESULTS: A total of 84,711 cases were
      identified of which 45.33% involved trainee participation. Odds ratios (ORs) and
      95% confidence interval for overall, neurologic, and bleeding complications were
      calculated. No difference in the odds of overall patient complications or
      neurologic complications was observed. A decrease in the odds of bleedings
      complications when a junior or senior trainee was present was observed. Overall
      complications in operations including a junior trainee (PGY 1-2) had an OR of
      1.04 (0.85, 1.29), a senior trainee (PGY 3-5) had an OR of 1.00 (0.89, 1.13), and
      a fellow had an OR of 0.98 (0.74, 1.31). Mean OT was found to be significantly
      different between attending only and junior and senior trainees. There was no
      significant difference in OT between fellows and attending only. LOS did not
      meaningfully differ across groups. CONCLUSIONS: In three commonly performed
      thyroid and parathyroid operations, there is not an increased overall or
      neurologic complication odds when a surgical trainee is involved; there are
      decreased odds of a bleeding complication.

PMID- 29180203
TI  - CEACAM1 is associated with recurrence after hepatectomy for colorectal liver
      metastasis.
AB  - BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)
      is re-expressed at the invasion front of colorectal cancer. CEACAM1 expression at
      metastatic sites remains to be investigated. The current study aims to clarify
      the association between CEACAM1 expression and recurrence after hepatectomy of
      colorectal liver metastasis and to address whether CEACAM1 induces tumor
      initiating properties needed for growth at metastatic sites. METHODS:
      Immunohistochemical analyses for CEACAM1 were performed in 67 patients with liver
      metastasis of colorectal cancer who had undergone curative hepatectomy. The risk
      factors for postoperative recurrence were calculated based on a CEACAM1
      cytoplasmic domain isoform at the primary tumor invasion front. To investigate
      the effects of CEACAM1 cytoplasmic isoforms on HT29 and HCT116 colorectal cancer
      cells, Western blotting for CD44 and CD133, flow cytometry for ALDH1 activity,
      and soft-agar colony formation assay were performed. RESULTS: CEACAM1 long
      (CEACAM1-L) and short (CEACAM1-S) cytoplasmic domain isoforms are strongly
      expressed on cancer cells in the liver metastases. Enhanced CEACAM1-S expression
      in the state of CEACAM1-L dominance at the primary tumor invasion front was an
      independent factor for colorectal cancer recurrence after curative hepatectomy.
      CEACAM1-4S-transfected HT29 and HCT116 cells had significantly higher CD44
      expression and ALDH1 activity and increased the growth in anchorage-independent
      condition. CONCLUSIONS: High expression of CEACAM1-S at the primary lesion
      invasion front is associated with recurrence and prognosis of patients with
      colorectal liver metastasis after curative hepatectomy. The expression of CEACAM1
      4S enhances the tumor-initiating property of colorectal cancer cells.

PMID- 29180204
TI  - Hyperoxygenated hydrogen-rich solution suppresses shock- and resuscitation
      induced liver injury.
AB  - BACKGROUND: It is not known whether simultaneous delivery of hydrogen and oxygen
      can reduce injury caused by hemorrhagic shock and resuscitation (HSR). This study
      investigated the therapeutic potential of hyperoxygenated hydrogen-rich solution
      (HHOS), a combined hydrogen/oxygen carrier, in a rat model of HSR-induced liver
      injury. MATERIALS AND METHODS: Rats (n = 60) were randomly divided into 5 groups
      (n = 6 per group at each time point). One group underwent sham operation, and the
      others were subjected to severe hemorrhagic shock and then treated with lactated
      Ringer's solution (LRS), hydrogen-rich solution, hyperoxygenated solution, or
      HHOS. At 2 and 6 h after resuscitation, blood samples (n = 6) were collected from
      the femoral artery and serum concentrations of alanine aminotransferase and
      aspartate aminotransferase (AST) were measured. Rats were then sacrificed, and
      histopathological changes in the liver were evaluated by quantifying the
      percentage of apoptotic cells by caspase-3 immunohistochemistry and terminal
      deoxynucleotidyl transferase dUTP nick-end labeling. Inflammation was assessed by
      assessing malondialdehyde content and tumor necrosis factor-alpha, and
      interleukin (IL)-6 expression. RESULTS: Compared to lactated Ringer's solution,
      hydrogen-rich solution, or hyperoxygenated solution groups, serum AST and alanine
      aminotransferase levels and IL-6, tumor necrosis factor-alpha, and
      malondialdehyde expression in liver tissue were decreased by HHOS treatment. The
      number of caspase-3- and terminal deoxynucleotidyl transferase dUTP nick end
      labeling-positive cells was decreased (P < 0.05) by HHOS treatment, 2 and 6 h
      after resuscitation. CONCLUSIONS: HHOS has protective effects against liver
      injury in a rat model of HSR.

PMID- 29180205
TI  - Effect of transfer status on outcomes for necrotizing soft tissue infections.
AB  - BACKGROUND: Whether patients with necrotizing soft tissue infections (NSTI) who
      presented to under-resourced hospitals are best served by immediate debridement
      or expedited transfer is unknown. We examined whether interhospital transfer
      status impacts outcomes of patients requiring emergency debridement for NSTI.
      METHODS AND MATERIALS: We conducted a retrospective review studying patients with
      an operative diagnosis of necrotizing fasciitis, Fournier's gangrene, or gas
      gangrene in the 2010-2015 American College of Surgeons National Surgical Quality
      Improvement Program Participant Use Data Files. Multivariable regression analyses
      determined if transfer status independently predicted 30-d mortality, major
      morbidity, minor morbidity, and length of stay. RESULTS: Among 1801 patients,
      1243 (69.0%) were in the non-transfer group and 558 (31.0%) were in the transfer
      group. The transfer group experienced higher rates of 30-d mortality (14.5%
      versus 13.0%) and major morbidity (64.5% versus 60.1%) than the non-transfer
      group, which were not significant after risk adjustment (adjusted odds ratio [95%
      confidence interval]: 0.87 [0.62-1.22] and 1.00 [0.79-1.27], respectively). The
      transferred group experienced a longer median length of postoperative
      hospitalization (14 d [interquartile range 8-24] versus 11 d [6-20]), which
      maintained statistical significance after adjustment for other factors (adjusted
      beta coefficient [95% confidence interval]: 1.92 [0.48-3.37]; P = 0.009).
      CONCLUSIONS: Our results suggest that interhospital transfer status is not an
      independent risk factor for mortality or morbidity after surgical management of
      NSTI. Although expedient debridement remains a basic tenet of NSTI management,
      our findings provide some reassurance that transfer before initial debridement
      will not significantly jeopardize patient outcomes should such transfer be deemed
      necessary.

PMID- 29180206
TI  - Ropivacaine wound infiltration: a fast-track approach in patients undergoing
      thoracotomy surgery.
AB  - BACKGROUND: Postoperative pain impairs enhanced recovery in patients after
      various surgeries. Local use of ropivacaine has become an effective strategy for
      postoperative pain management. The aim of this study was to assess the
      effectiveness and safety of wound infiltration with ropivacaine for postoperative
      analgesia as a fast-track approach in patients undergoing thoracotomy surgery.
      MATERIALS AND METHODS: Forty adult patients with esophageal cancer scheduled for
      selective thoracotomy surgery were enrolled in this double-blind, randomized,
      controlled study. Patients were randomized (1:1) to receive ropivacaine or
      placebo wound infiltration before incision closure. Numerical rating score (NRS),
      postoperative analgesics consumption, length of hospital stay, time to anal
      exsufflation, defecation, ambulation, and patient satisfaction scores were
      recorded. Side effects including allergic reaction, nausea, vomiting, wound
      infection, and pneumonia were also assessed. RESULTS: NRS was significantly
      decreased in the ropivacaine group with less consumption of postsurgery
      analgesics. The ropivacaine group also showed shorter postoperative hospital
      stays, earlier anal exsufflation and ambulation, and higher patient satisfaction
      scores. However, there were no significant differences between the two groups
      regarding time of defecation. No allergic reactions occurred in either group. The
      incidences of nausea, vomiting, wound infection, and pneumonia were similar.
      CONCLUSIONS: The present study showed that ropivacaine wound infiltration could
      be a safe and effective fast-track approach for patients undergoing thoracotomy
      surgery.

PMID- 29180207
TI  - Residents' response to bleeding during a simulated robotic surgery task.
AB  - BACKGROUND: The aim of this study was to assess performance measurement validity
      of our newly developed robotic surgery task trainer. We hypothesized that
      residents would exhibit wide variations in their intercohort performance as well
      as a measurable difference compared to surgeons in fellowship training. MATERIALS
      AND METHODS: Our laboratory synthesized a model of a pelvic tumor that simulates
      unexpected bleeding. Surgical residents and fellows of varying specialties
      completed a demographic survey and were allowed 20 minutes to resect the tumor
      using the da Vinci robot and achieve hemostasis. At a standardized event in the
      simulation, venous bleeding began, and participants attempted hemostasis using
      suture ligation. A motion tracking system, using electromagnetic sensors,
      recorded participants' hand movements. A postparticipation Likert scale survey
      evaluated participants' assessment of the model's realism and usefulness.
      RESULTS: Three of the seven residents (postgraduate year 2-5), and the fellow
      successfully resected the tumor in the allotted time. Residents showed high
      variability in performance and blood loss (125-700 mL) both within their cohort
      and compared to the fellow (150 mL blood). All participants rated the model as
      having high realism and utility for trainees. CONCLUSIONS: The results support
      that our bleeding pelvic tumor simulator has the ability to discriminate resident
      performance in robotic surgery. The combination of motion, decision-making, and
      blood loss metrics offers a multilevel performance assessment, analyzing both
      technical and decision-making abilities.

PMID- 29180208
TI  - MZB1 in borderline resectable pancreatic cancer resected after neoadjuvant
      chemoradiotherapy.
AB  - BACKGROUND: A high accumulation of CD8+ tumor-infiltrating lymphocytes (TILs)
      induced by neoadjuvant chemoradiotherapy (NACRT) is associated with a favorable
      prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the
      correlation between a high accumulation of CD8+ TILs and a favorable prognosis
      has yet to be fully clarified. The aim of this study was to determine predictive
      markers of a high accumulation of CD8+ TILs, with a favorable prognosis, using
      proteomic analysis. MATERIALS AND METHODS: We studied 72 resected borderline
      resectable PDAC patients treated with NACRT between April 2009 and March 2014.
      Three matched pairs of high CD8+ TIL patients with a favorable prognosis and low
      CD8+ TIL patients with a poor prognosis were selected. Shotgun proteomics of the
      stroma and cancerous lesion was performed using formalin-fixed, paraffin-embedded
      tissue. Validation of the identified proteins was performed using
      immunohistochemical staining. Relationships between the identified proteins and
      TILs and clinical outcomes were assessed. RESULTS: Marginal zone B- and B1-cell
      specific protein (MZB1) was detected in the tumor stroma. MZB1 expression was
      positively correlated with a high accumulation of CD8+ TILs. High stromal MZB1
      expression also correlated with disease-free and overall survival. In a subgroup
      analysis of CD8+ expression, there was a significant association between stromal
      MZB1 expression and disease-free and overall survival in the high CD8+ TIL group.
      CONCLUSIONS: MZB1 is a potential marker of a high accumulation of CD8+ TILs in
      borderline resectable PDACs resected after NACRT. Combination of CD8+ TILs with
      MZB1 may be a new biomarker of resected cases after NACRT.

PMID- 29180209
TI  - Costunolide protects lipopolysaccharide/d-galactosamine-induced acute liver
      injury in mice by inhibiting NF-kappaB signaling pathway.
AB  - BACKGROUND: Costunolide, a well-known sesquiterpene lactone, has been reported to
      have anti-inflammatory and anti-oxidative effects. METHODS: In this study, we aim
      to investigate the protective effects and mechanism of costunolide on
      lipopolysaccharide/d-galactosamine (LPS/D-Gal)-induced acute liver injury. Acute
      liver injury animal model was induced by intraperitoneal injection with D-Gal and
      LPS. Costunolide (10, 20, and 30 mg/kg) was injected intraperitoneally 1 h before
      or after LPS/D-Gal treatment. RESULTS: The results showed that costunolide
      significantly attenuated liver pathologic changes, as well as alanine
      aminotransferase and aspartate aminotransferase levels in serum. Meanwhile,
      costunolide inhibited the expressions of interleukin (IL-1beta) and tumor
      necrosis factor (TNF-alpha) in liver tissues in a dose-dependent manner.
      Furthermore, costunolide dose dependently inhibited LPS/D-Gal-induced NF-kappaB
      activation. CONCLUSIONS: In conclusion, this study suggested that costunolide
      could attenuate LPS/D-Gal-induced liver injury and might be a potential
      therapeutic reagent for liver injury.

PMID- 29180210
TI  - Survival outcomes of neoadjuvant chemotherapy with zoledronic acid for HER2
      negative breast cancer.
AB  - BACKGROUND: A randomized phase 2 trial in women with HER2-negative breast cancer
      has shown that adding zoledronic acid (ZOL) to neoadjuvant chemotherapy (CT) has
      potential anticancer benefits in postmenopausal and triple-negative (TN) breast
      cancer patients. We report the data for the secondary end point of disease-free
      survival (DFS). METHODS: Patients were randomly assigned to receive CT or CT +
      ZOL (CT-Z). All patients received four cycles of FEC100 followed by 12 cycles of
      paclitaxel weekly. ZOL (4 mg) was administered 3-4 times weekly for 7 wk to the
      CT-Z group patients. The primary end point was pathologic complete response
      (pCR). The secondary end points were the clinical response rates, rate of breast
      conserving surgery, safety, and DFS. RESULTS: Of the 188 patients enrolled, 95
      were assigned to the CT group and 93 to the CT-Z group. DFS and overall survival
      were analyzed in 92 and 88 patients with the mean times of 5.15 y and 5.38 y,
      respectively. The 3-y DFS rate was 84.6% in the CT group and 90.8% in the CT-Z
      group (P = 0.188). The particular benefit from ZOL for the neoadjuvant CT seen as
      improvement of the pCR rate was indicated in the 3-y DFS period for TN cancer
      cases (CT versus CT-Z: 70.6% versus 94.1%) but not for postmenopausal cases.
      CONCLUSIONS: ZOL did not improve DFS when combined with CT. However, the
      improvement of the pCR rate translated to survival outcomes in TN breast cancer.
      The short-term application of ZOL may not be sufficient to improve the outcome in
      postmenopausal patients.

PMID- 29180211
TI  - Open versus laparoscopic approach to gastric fundoplication in children with
      cardiac risk factors.
AB  - BACKGROUND: Gastric fundoplication is the most common noncardiac operation in
      children with congenital cardiac disease. While prior studies validated safety of
      laparoscopy in this population, we hypothesize that children with cardiac risk
      factors (CRFs) are likelier to undergo open fundoplication (OF) but experience
      greater morbidity than after laparoscopic fundoplication (LF). MATERIALS AND
      METHODS: Utilizing 2013 National Surgical Quality Improvement Program-Pediatrics
      Public-Use-File, pediatric patients undergoing LF and OF were stratified to none,
      minor, major, or severe CRFs. Multivariate logistic regression determined
      preoperative variables and postoperative outcomes associated with LF or OF.
      RESULTS: A total of 1501 fundoplication patients were identified with 92%
      undergoing LF. OF patients were likelier to have minor (odds ratio [OR]: 2.36, P
      < 0.001), major (OR: 2.41, P = 0.003), and severe CRFs (OR: 4.36, P < 0.001).
      Children <= 1 y (OR: 3.38, P = 0.048) and those with tracheostomy were likelier
      to have OF (OR: 2.3, P = 0.006). Overall, the OF group had higher postoperative
      morbidity (OR: 2.41, P < 0.001). Specifically, children with minor or major CRFs
      experienced more complications following OF compared to LF. CONCLUSIONS: OF is
      more common in patients <=1 y old; patients with minor, major, or severe CRFs;
      and those with tracheostomy. LF should be considered in children with minor and
      major CRFs, as OF in those patients results in greater pulmonary, infectious, and
      hematological sequelae.

PMID- 29180212
TI  - Patterns of elective lobectomy for lung cancer.
AB  - BACKGROUND: Lobectomy is the recommended treatment for early-stage lung cancer.
      Little is known about variations of access to health service areas and hospital
      types for lobectomy overall and according to specific surgical techniques, such
      as the video-assisted thoracoscopic surgery (VATS). METHODS: The New York
      Statewide Planning and Research Cooperative System (2007-2012) was queried for
      lung cancer patients who underwent elective lobectomy. Hospitals were defined as
      nearest high-volume hospital (nHVH, reference), distant HVH (dHVH), close or
      distant low-volume hospital (cLVH or dLVH) using lobectomy volume and travel
      burden by the distance to nHVH. RESULTS: Utilization of hospitals within
      patients' health service areas ranged between 44% and 82% for three different
      geographic units. Approximately 26%, 34%, 31%, and 9% of the 9099 lobectomies
      were performed in nHVH, dHVH, cLVH, and dLVH, respectively. Patients in nHVH were
      older and more likely to have private insurance. Patients in dHVH were treated
      more with VATS and by higher volume surgeons, opposite of what observed in cLVH
      and dLVH. The use of dHVH was associated with more comorbidities and higher
      income. The use of dLVH was higher in Hispanics and non-Hispanic blacks than that
      in non-Hispanic whites. The odds of adverse postoperative events were higher in
      cLVH and dLVH but lower for patients treated with VATS and by high-volume
      surgeons. CONCLUSIONS: Multiple factors likely resulted in differences in
      patterns of elective lobectomy among lung cancer patients. These variations
      should be taken into account when accessing and planning specialized health care
      delivery services.

PMID- 29180213
TI  - Cross talk between TGF beta and TNF alfa in regression of myointimal hyperplasia.
AB  - BACKGROUND: The phenomena involved in regression of arterial myointimal
      hyperplasia have not been analyzed in detail. MATERIALS AND METHODS: In 24 Lewis
      rats, a 1-cm-long venous graft, obtained from syngenic Lewis rats, was implanted
      in the infrarenal aorta. After 4 wk, the grafts were removed and analyzed using
      scanning electron microscopy and histochemistry. The grafts showed evidence of
      myointimal hyperplasia; 16 of these explanted grafts were reimplanted in the vein
      circulation of syngenic Lewis rats. These grafts were harvested 2 wk (8 animals)
      and 8 wk (8 animals) later, showing complete regression of myointimal
      hyperplasia. RESULTS: Regression of experimental myointimal hyperplasia was
      correlated with the simultaneous and complementary action of Transforming Growth
      Factor beta and Tumor Necrosis Factor alfa. Inflammatory cytokines (IL1, IL2, and
      IL6) inhibit Tumor Necrosis Factor alfa-induced apoptosis. CONCLUSIONS:
      Regression of myointimal hyperplasia is an active process, which implies the
      action of several inhibitory factors. The analysis of these phenomena can lead to
      new therapeutic approaches to prevent myointimal hyperplasia progression.

PMID- 29180214
TI  - Thioredoxin-1 attenuates sepsis-induced cardiomyopathy after cecal ligation and
      puncture in mice.
AB  - BACKGROUND: Sepsis is a leading cause of mortality among patients in intensive
      care units across the USA. Thioredoxin-1 (Trx-1) is an essential 12 kDa cytosolic
      protein that, apart from maintaining the cellular redox state, possesses
      multifunctional properties. In this study, we explored the possibility of
      controlling adverse myocardial depression by overexpression of Trx-1 in a mouse
      model of severe sepsis. METHODS: Adult C57BL/6J and Trx-1Tg/+ mice were divided
      into wild-type sham (WTS), wild-type cecal ligation and puncture (WTCLP), Trx
      1Tg/+sham (Trx-1Tg/+S), and Trx-1Tg/+CLP groups. Cardiac function was evaluated
      before surgery, 6 and 24 hours after CLP surgery. Immunohistochemical and Western
      blot analysis were performed after 24 hours in heart tissue sections. RESULTS:
      Echocardiography analysis showed preserved cardiac function in the Trx-1Tg/+ CLP
      group compared with the WTCLP group. Similarly, Western blot analysis revealed
      increased expression of Trx-1, heme oxygenase-1 (HO-1), survivin (an inhibitor of
      apoptosis [IAP] protein family), and decreased expression of thioredoxin
      interacting protein (TXNIP), caspase-3, and 3- nitrotyrosine in the Trx-1Tg/+CLP
      group compared with the WTCLP group. Immunohistochemical analysis showed reduced
      4-hydroxynonenal, apoptosis, and vascular leakage in the cardiac tissue of Trx
      1Tg/+CLP mice compared with mice in the WTCLP group. CONCLUSIONS: Our results
      indicate that overexpression of Trx-1 attenuates cardiac dysfunction during CLP.
      The mechanism of action may involve reduction of oxidative stress, apoptosis, and
      vascular permeability through activation of Trx-1/HO-1 and anti-apoptotic protein
      survivin.

PMID- 29180215
TI  - Analysis of ischemic muscle in patients with peripheral artery disease using X
      ray spectroscopy.
AB  - BACKGROUND: Peripheral artery disease (PAD) is a vascular disease caused by
      atherosclerosis, resulting in decreased blood flow to the lower extremities. The
      ankle-brachial index (ABI) is a standard PAD diagnostic test but only identifies
      reduced blood flow based on blood pressure differences. The early signs of PAD
      manifest themselves not only at a clinical level but also at an elemental and
      biochemical level. However, the biochemical and elemental alterations to PAD
      muscle are not well understood. The objective of this study was to compare
      fundamental changes in intracellular elemental compositions between control,
      claudicating, and critical limb ischemia muscle tissue. MATERIALS AND METHODS:
      Gastrocnemius biopsies from three subjects including one control (ABI >= 0.9),
      one claudicating (0.4 <= ABI < 0.9), and one critical limb ischemia patient (ABI
      < 0.4) were evaluated using a scanning electron microscope and energy dispersive
      X-ray spectroscopy to quantify differences in elemental compositions. Spectra
      were collected for five myofibers per specimen. An analysis of variance was
      performed to identify significant differences in muscle elemental compositions.
      RESULTS: This study revealed that intracellular magnesium and calcium were lower
      in PAD compared with control myofibers, whereas sulfur was higher. Magnesium and
      calcium are antagonistic, meaning, if magnesium concentrations go down calcium
      concentrations should go up. However, our findings do not support this antagonism
      in PAD. Our analysis found decreases in sodium and potassium, in PAD myofibers.
      CONCLUSIONS: These findings may provide insight into the pathologic mechanisms
      that may operate in ischemic muscle and aid in the development of specialized
      preventive and rehabilitative treatment plans for PAD patients.

PMID- 29180216
TI  - Pediatric gastrostomy tubes and techniques: making safer and cleaner choices.
AB  - BACKGROUND: Gastrostomy tube placement is a common procedure that can be
      accomplished with a variety of techniques, each with its attendant complications.
      In an effort to standardize practice at our institution, we retrospectively
      evaluated complications including early dislodgement requiring operative repair,
      leaks, and granulation tissue to determine the optimal technique. MATERIALS AND
      METHODS: A retrospective cohort study (June 2008-July 2014) evaluating children
      (<18) receiving gastrostomy tubes was completed. We recorded demographic data,
      placement technique, and postoperative complications within 120 days. The seven
      techniques in use at our institution were categorized into three groups: standard
      pull-type techniques for percutaneous endoscopic gastrostomies (PEGs), "push"
      techniques using transabdominal sutures or T-fasteners for securement of the
      stomach, and "fascial" techniques using sutures directly from the stomach to the
      abdominal fascia at the stoma site. Descriptive statistics were analyzed using t
      test and Kruskal-Wallis tests as appropriate, and outcomes with P < 0.05 were
      considered significant. RESULTS: Of the 450 patients, 255 (56.7%) were male.
      Median age and weight at the time of operation were 19.3 months (interquartile
      range, 6.5-89.6 months) and 9.0 kg (interquartile range, 5.7-17.1 kg)
      respectively. By technique, 245 patients underwent fascial placement (54.4%), 112
      underwent push (24.9 %), and 93 underwent PEG (20.7%). Push and fascial
      techniques were less likely become dislodged than PEG, with odds ratios (ORs) of
      0.14 (confidence interval CI 0.02-0.66) and 0.31 (CI 0.11-0.83), respectively.
      Fascial techniques had more granulation tissue than either push or PEG pull
      methods, OR 2.39 (CI 1.20-3.36), and more leakage, OR 2.22 (CI 1.19-4.15).
      CONCLUSIONS: Dislodgement is most likely with PEG techniques. Granulation and
      leakage are most likely with fascial suture techniques. Push techniques are
      associated with the lowest complication rate.

PMID- 29180217
TI  - Comparison of perioperative complications of pedicled island flap in
      reconstruction of extremities.
AB  - PURPOSE: The aim of this study was to analyze the differences in perioperative
      complications for pedicled island flaps in the reconstruction of extremities and
      to identify the factors contributing to pedicled island flap necrosis.
      Furthermore, the flap indications based on these outcomes are summarized.
      METHODS: Based on the inclusion criteria, 228 skin flaps were included in this
      study. Univariate and multivariate analyses were used to identify the risk
      factors for pedicled island flap necrosis. Differences in perioperative
      complications between upper and lower extremities were analyzed using the chi
      square test or Fisher's exact test. RESULTS: The average age of the patients was
      38 years. The overall complication rate was 21.93%, including partial flap
      necrosis (10.09%) and total flap necrosis (5.70%). The overall complication rate
      and flap necrosis rate in upper extremity reconstruction were significantly lower
      than the rates in lower extremity reconstruction. Flap area and postoperative
      wound infection were statistically significant risk factors for pedicled island
      flap necrosis in extremity reconstruction. Preoperative contamination of the
      wound bed was a statistically significant risk factor for postoperative wound
      infection. CONCLUSIONS: The flap area and postoperative wound infection were both
      independent risk factors for pedicled island flap necrosis in extremity
      reconstruction. The causes contributing to the differences in perioperative
      complications between upper and lower extremities reconstruction included
      preoperative contamination of the wound bed, postoperative wound infection, and
      the flap area but were also related to anatomical factors of the skin flap.
      Pedicled island flaps are more suitable for small- and medium-sized soft tissue
      defects.

PMID- 29180218
TI  - A high-throughput solid-phase microextraction and post-loop mixing large volume
      injection method for water samples.
AB  - This article presents a novel approach for the analysis of 13 drugs in wastewater
      for use in wastewater-based epidemiology (WBE) studies. Sample preparation
      remains one of the principal bottlenecks in modern high-throughput analysis by
      ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC
      MS/MS). The proposed methodology is based on the micro-extraction of small
      volumes (1 ml) of wastewater using a HLB 96-well microplate and both large volume
      injection (LVI) and post-loop mixing injection (PLM). With this configuration,
      the limits of quantification (LOQ) were below the reported environmental
      concentrations of the target compounds in wastewater. Furthermore, both the
      complexity of collecting, transporting and storing the wastewater sample, sample
      preparation time, cost and amount of solvent used are all diminished, enhancing
      the suitability of this methodology for future WBE studies. A new workflow is
      also proposed in order to create a virtual specimen library bank for WBE by using
      high-resolution mass spectrometry (HRMS). The method was validated and the limits
      of quantification were between 0.2 and 6.3 ng L-1. The relative standard
      deviations (RSD) for a standard mixture at 200 ng L-1 (n = 6) was between 3.4 and
      14.4% while the recoveries for the 13 drug target residues (DTR) were between 92
      and 110%. The developed and validated method was finally successfully applied to
      10 wastewater samples collected from Oslo, Norway.

PMID- 29180219
TI  - Rapid method for the quantification of 13 sulphonamides in milk by conventional
      high-performance liquid chromatography with diode array ultraviolet detection
      using a column packed with core-shell particles.
AB  - In the present study, a column packed with core-shell particles was used for the
      separation and the quantification of 13 sulphonamides in milk by conventional
      high-performance liquid chromatography coupled with diode array ultraviolet
      detection (HPLC/UV-DAD). Preliminary experiments were carried out to investigate
      selectivity of different stationary phases. Best results were achieved using a
      C18 column packed with 2.6MUm core-shell particles (diameter 4.6mm, length 75mm).
      A binary gradient elution based on acetate buffer solution at pH 4.50 and a
      mixture of methanol acetonitrile 50:50 (v/v) was employed at the flow rate of
      1.2mLmin-1 with an injection volume of 6MUL. These chromatographic conditions
      allowed the efficient separation of 13 sulphonamides in about 8min. To evaluate
      the suitability of the method for official control analysis, the most important
      validation parameters were investigated according to the European Decision
      657/2002/EC as established for analysis of drug residues in food. Sulphonamides
      were recovered from milk samples by a simple and quick preparation procedure
      consisting of an extraction step with chloroform/acetone and a purification step
      with n-hexane. Mean recoveries from raw milk ranged between 55% and 86% at the
      Maximum Residual Limit of 100MUgkg-1, and RSDs% resulted lower than Thompson and
      Horwitz RSD% reference values for all sulphonamides. The LOQ value (2.7-15MUgkg
      1) was low enough to satisfy legal limits suggested by European Regulation
      37/2010/EC.

PMID- 29180220
TI  - Organic solvent modifier and temperature effects in non-aqueous size-exclusion
      chromatography on reversed-phase columns.
AB  - Common reversed-phase columns (C18, C4, phenyl, and cyano) offer inert surfaces
      suitable for the analysis of polymers by size-exclusion chromatography (SEC). The
      effect of tetrahydrofuran (THF) solvent and the mixtures of THF with a variety of
      common solvents used in high performance liquid chromatography (acetonitrile,
      methanol, dimethylformamide, 2-propanol, ethanol, acetone and chloroform) on
      reversed-phase stationary phase characteristics relevant to size exclusion were
      studied. The effect of solvent on the elution of polystyrene (PS) and poly(methyl
      methacrylate) (PMMA) and the effect of column temperature (within a relatively
      narrow range corresponding to typical chromatographic conditions, i.e., 10
      degrees C-60 degrees C) on the SEC partition coefficients KSEC of PS and PMMA
      polymers, were also investigated. The bonded phases show remarkable differences
      in size separations when binary mixtures of THF with other solvents are used as
      the mobile phase. The solvent impact can be two-fold: (i) change of the polymeric
      coil size, and possible shape, and (ii) change of the stationary phase pore
      volume. If the effect of this impact is properly moderated, then the greatest
      benefit of optimized solute resolution can be achieved. Additionally, this work
      provides an insight on solvent-stationary phase interactions and their effects on
      column pore volume. The only effect of temperature observed in our studies was a
      decreased elution volume of the polymers with increasing temperature. SEC
      partition coefficients were temperature-independent in the range of 10 degrees C
      60 degrees C and therefore, over this temperature range elution of PS and PMMA
      polymers is by near-ideal SEC on reversed-phase columns. Non-ideal SEC appears to
      occur for high molar mass PMMA polymers on a cyano column when alcohols are used
      as mobile phase modifiers.

PMID- 29180221
TI  - Performance optimization of ultra high-resolution recycling liquid
      chromatography.
AB  - The optimization of a twin-column recycling separation process (TCRSP) for
      maximum resolution or maximum speed-resolution was investigated. The general
      optimization method was based on the construction of kinetic plots by assuming an
      ideal TCRSP (no efficiency loss upon recycling). For the optimization, we
      examined three chromatographic parameters: operation pressure (3000, 6000, 9000,
      and 12,000psi), column length (10, 15, and 25cm), and column inner diameter
      (i.d.) (2.1, 3.0, and 4.6mm). Accordingly, the highest TCRSP resolution level is
      expected for 25cm long columns packed with 2.5, 2.0, 1.7, and 1.6MUm particles at
      pressures of 3000, 6000, 9000, and 12,000psi, respectively. The maximum speed
      resolution performance is expected for 10cm columns packed with 3.7, 3.0, 2.6,
      and 2.4MUm particles. 3.0mm i.d. columns are best to minimize the negative
      impacts of thermal and inter-column dispersion effects on the TCRSP performance.
      The method was illustrated for the challenging separation (selectivity factor
      alpha<1.02) of small molecules in RPLC at a maximum pressure of 6000psi using
      commercially available columns. Accordingly, 3.0*150mm columns packed with 2.5MUm
      cellulose-1 Trefoil particles (chiral separation, gamma-phenylbutyrolactone,
      alpha=1.01, efficiency N=4500) and 2.7MUm Cortecs-C18 particles (isotope
      separation, alpha=1.02, N=14, 500) particles were found to be the most suitable
      columns to maximize speed-resolution performance. Further optimization of the
      TCRSP performance was required by reducing the inter-column sample dispersion
      that could cause undesirable peak tailing. A standard 2.4MUL Rheodyne valve and
      100MUm i.d. tubes were replaced with a home-made 0.5MUL low-dispersion prototype
      valve and 75MUm i.d. perfect connection tubes. As a result, the experimental
      resolution factors were increased by +60% (gamma-phenylbutyrolactone, 25 cycles,
      Rs=0.7->1.1) and +80% (deuterated benzenes, 22 cycles, Rs=1.1->2.0). Direct
      comparison between the experimental and the predicted TCRSP performance
      unambiguously demonstrated that the resolution gain was explained by the
      significant reduction of the peak tailing after a large number of cycles (n>20).

PMID- 29180222
TI  - Intranasal insulin in Alzheimer's disease: Food for thought.
AB  - Accumulating evidence suggests that disrupted brain insulin signaling promotes
      the development and progression of Alzheimer's disease (AD), driving clinicians
      to target this circuitry. While both traditional and more modern antidiabetics
      show promise in combating insulin resistance, intranasal insulin appears to be
      the most efficient method of boosting brain insulin. Furthermore, intranasal
      delivery elegantly avoids adverse effects from peripheral insulin administration.
      However, there remain significant open questions regarding intranasal insulin's
      efficacy, safety, and potential as an adjunct or mono-therapy. Thus, this review
      aims to critically evaluate the present evidence and future potential of
      intranasal insulin as a meaningful treatment for AD. This article is part of the
      Special Issue entitled 'Metabolic Impairment as Risk Factors for
      Neurodegenerative Disorders.'

PMID- 29180223
TI  - Insulin resistance, an unmasked culprit in depressive disorders: Promises for
      interventions.
AB  - Depressive disorders constitute a set of debilitating diseases with
      psychological, societal, economic and humanitarian consequences for millions of
      people worldwide. Scientists are beginning to understand the reciprocal
      communication between the brain and the rest of the body in the etiology of these
      diseases. In particular, scientists have noted a connection between depressive
      disorders, which are primarily seen as brain-based, and, insulin resistance (IR),
      a modifiable metabolic inflammatory state that is typically seen as peripheral.
      We highlight evidence showing how treating IR, with drugs or behavioral
      interventions, may ameliorate or possibly prevent, depressive disorders and their
      long-term consequences at various stages of the life course. This article is part
      of the Special Issue entitled 'Metabolic Impairment as Risk Factors for
      Neurodegenerative Disorders.'

PMID- 29180224
TI  - A regulatory perspective on the evaluation of hallucinogen drugs for human use.
AB  - In recent years, there is renewed interest in the study of various hallucinogens
      for their potential therapeutic effects. In the United States of America (USA),
      the abuse potential assessment of a drug is carried out as part of the general
      safety and efficacy evaluation of a drug. Additionally, the abuse potential
      assessment is taken under consideration in determining if a drug needs to be
      subject to controls to minimize the abuse of the drug once on the market. This
      assessment is conducted for all new drugs with central nervous system (CNS)
      activity, that are chemically or pharmacologically similar to other drugs with
      known abuse potential, or drugs that produce psychoactive effects predictive of
      abuse, such as euphoria and hallucinations. This paper describes the regulatory
      framework for evaluating the abuse potential of new drugs, with emphasis on
      hallucinogens. The paper discusses the role of the United States Food and Drug
      Administration (FDA) in the evaluation of the abuse potential of drugs and its
      role in drug control, and provides an overview of the controlled status of
      hallucinogens and the requirements to conduct research with Schedule I substances
      in the USA. This article is part of the Special Issue entitled 'Psychedelics: New
      Doors, Altered Perceptions'.

PMID- 29180225
TI  - Ferrosenescence: The iron age of neurodegeneration?
AB  - Aging has been associated with iron retention in many cell types, including the
      neurons, promoting neurodegeneration by ferroptosis. Excess intracellular iron
      accelerates aging by damaging the DNA and blocking genomic repair systems, a
      process we define as ferrosenescence. Novel neuroimaging and proteomic techniques
      have pinpointed indicators of both iron retention and ferrosenescence, allowing
      for their early correction, potentially bringing prevention of neurodegenerative
      disorders within reach. In this review, we take a closer look at the early
      markers of iron dyshomeostasis in neurodegenerative disorders, focusing on
      preventive strategies based on nutritional and microbiome manipulations.

PMID- 29180226
TI  - Microwave radiation leading to shrinkage of dendritic spines in hippocampal
      neurons mediated by SNK-SPAR pathway.
AB  - The popularization of microwave raised concerns about its influence on health
      including cognitive function which is associated greatly with dendritic spines
      plasticity. SNK-SPAR is a molecular pathway for neuronal homeostatic plasticity
      during chronically elevated activity. In this study, Wistar rats were exposed to
      microwaves (30 mW/cm2 for 6 min, 3 times/week for 6 weeks). Spatial learning and
      memory function, distribution of dendritic spines, ultrastructure of the neurons
      and their dendritic spines in hippocampus as well as the related critical
      molecules of SNK-SPAR pathway were examined at different time points after
      microwave exposure. There was deficiency in spatial learning and memory in rats,
      loss of spines in granule cells and shrinkage of mature spines in pyramidal
      cells, accompanied with alteration of ultrastructure of hippocampus neurons.
      After exposure to 30 mW/cm2 microwave radiation, the up-regulated SNK induced
      decrease of SPAR and PSD-95, which was thought to cause the changes mentioned
      above. In conclusion, the microwave radiation led to shrinkage and even loss of
      dendritic spines in hippocampus by SNK-SPAR pathway, resulting in the cognitive
      impairments.

PMID- 29180227
TI  - Mechanism of salvianolic acid B neuroprotection against ischemia/reperfusion
      induced cerebral injury.
AB  - The purpose of this study was to evaluate the cerebral protection of salvianolic
      acid B (Sal B) against cerebral I/R injury and investigate the underlying
      mechanism. As shown by 2,3,5-Triphenyltetrazolium chloride (TTC) staining and
      magnetic resonance imaging (MRI) analyses, Sal B significantly reduced cerebral
      infarct size, and accompanied with improved neurobehavioral functions as
      indicated by the modified Bederson score and Longa five-point scale. Sal B
      decreased the production of reactive oxygen species (p < .05, n = 10). The data
      of Western blotting and reverse transcription quantitative real time polymerase
      chain reaction (qRT-PCR) analyses showed that the expression of GFAP, Iba1, IL
      1beta, IL-6, TNF-alpha and Cleaved-caspase 3 was significantly reduced by Sal B
      in I/R injured brain tissues as compared to corresponding controls (p < .05, n =
      10). Over activation of astrocytes and microglia were inhibited by Sal B as shown
      by immunostaining of GFAP and Iba 1. These data suggest that Sal B has neural
      protective effects against I/R-induced cerebral injury and could be an effective
      candidate for further development of clinical therapy.

PMID- 29180228
TI  - Telehealth and telenursing using simulation for pre-licensure USA students.
AB  - An innovative simulation was used to teach pre-licensure USA nursing students
      about telenursing for screening, assessment, and patient education during a home
      visit. The students used telepresence technology to deliver nursing care to a
      homebound geriatric patient. After the simulation, students (N = 73) felt
      increased confidence with the skills needed to deliver telenursing care and in
      using telepresence technology. Students reported that they modified and improved
      their communication in order to adapt to perceived barriers posed by the new
      technology. As telenursing becomes more prevalent for managing patient care at a
      distance, nursing programs will need to incorporate educational strategies to
      reflect this change.

PMID- 29180230
TI  - Glucocorticoids, genes and brain function.
AB  - The identification of key genes in transcriptomic data constitutes a huge
      challenge. Our review of microarray reports revealed 88 genes whose transcription
      is consistently regulated by glucocorticoids (GCs), such as cortisol,
      corticosterone and dexamethasone, in the brain. Replicable transcriptomic data
      were combined with biochemical and physiological data to create an integrated
      view of the effects induced by GCs. The most frequently reported genes were
      Errfi1 and Ddit4. Their up-regulation was associated with the altered
      transcription of genes regulating growth factor and mTORC1 signaling (Gab1,
      Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1,
      Cdkn1a and Cables1). The GC-induced reprogramming of cell function involves
      changes in the mRNA level of genes responsible for the regulation of
      transcription (Klf9, Bcl6, Klf15, Tle3, Cxxc5, Litaf, Tle4, Jun, Sox4, Sox2,
      Sox9, Irf1, Sall2, Nfkbia and Id1) and the selective degradation of mRNA (Tob2).
      Other genes are involved in the regulation of metabolism (Gpd1, Aldoc and Pdk4),
      actin cytoskeleton (Myh2, Nedd9, Mical2, Rhou, Arl4d, Osbpl3, Arhgef3, Sdc4, Rdx,
      Wipf3, Chst1 and Hepacam), autophagy (Eva1a and Plekhf1), vesicular transport
      (Rhob, Ehd3, Vps37b and Scamp2), gap junctions (Gjb6), immune response (Tiparp,
      Mertk, Lyve1 and Il6r), signaling mediated by thyroid hormones (Thra and
      Sult1a1), calcium (Calm2), adrenaline/noradrenaline (Adcy9 and Adra1d),
      neuropeptide Y (Npy1r) and histamine (Hdc). GCs also affected genes involved in
      the synthesis of polyamines (Azin1) and taurine (Cdo1). The actions of GCs are
      restrained by feedback mechanisms depending on the transcription of Sgk1, Fkbp5
      and Nr3c1. A side effect induced by GCs is increased production of reactive
      oxygen species. Available data show that the brain's response to GCs is part of
      an emergency mode characterized by inactivation of non-core activities,
      restrained inflammation, restriction of investments (growth), improved efficiency
      of energy production and the removal of unnecessary or malfunctioning cellular
      components to conserve energy and maintain nutrient supply during the stress
      response.

PMID- 29180229
TI  - Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based
      chemotherapy.
AB  - Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity.
      Doxorubicin promotes thinning of the brain cortex and accelerates brain aging,
      leading to cognitive impairment. Oxidative stress induced by doxorubicin
      contributes to cellular damage. In addition to mitochondria, peroxisomes also
      generate reactive oxygen species (ROS) and promote cell senescence. Here, we
      investigated if doxorubicin affects peroxisomal homeostasis in neurons. We
      demonstrate that the number of peroxisomes is increased in doxorubicin-treated
      neurons and in the brains of mice which underwent doxorubicin-based chemotherapy.
      Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons,
      and peroxisomes produce more ROS. 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD),
      an activator of the transcription factor TFEB, which regulates expression of
      genes involved in autophagy and lysosome function, mitigates damage of pexophagy
      and decreases ROS production induced by doxorubicin. We conclude that peroxisome
      associated oxidative stress induced by doxorubicin may contribute to
      neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer
      patients and survivors. Peroxisomes might be a valuable new target for mitigating
      neuronal damage caused by chemotherapy drugs and for slowing down brain aging in
      general.

PMID- 29180231
TI  - Regional gray matter volume and structural network strength in somatic vs. non
      somatic delusional disorders.
AB  - BACKGROUND: Monothematic delusional disorders are characterized by a single
      tenacious belief. They provide a great opportunity to study underlying brain
      structures in the absence of confounding symptoms that accompany delusions in
      schizophrenia. Delusional beliefs include persecution, jealousy or somatic
      delusions including infestation. It is unclear whether specific delusional
      content is associated with distinct neural substrates. METHODS: We used magnetic
      resonance imaging in patients presenting with somatic vs. non-somatic delusional
      disorders. Patients with delusional infestation (DI, n=18), and individuals with
      non-somatic delusional disorders (n=19) were included, together with healthy
      volunteers (n=20). Uni- and multivariate techniques for structural data analysis
      were applied to provide a comprehensive characterization of abnormal brain volume
      at both the regional and neural network level. RESULTS: Patients with DI showed
      lower gray matter volume in thalamic, striatal (putamen), insular and medial
      prefrontal brain regions in contrast to non-somatic delusional disorders and
      healthy controls. Importantly, these differences were consistently detected at
      regional and network level. Compared to healthy controls, patients with
      delusional disorders other than DI showed lower gray matter volume in temporal
      cortical regions. CONCLUSION: The data support the notion that dysfunctional
      somatosensory and peripersonal networks could mediate somatic delusions in
      patients with DI in contrast to delusional disorders without somatic content. The
      data also suggest putative content-specific neural signatures in delusional
      disorders and in delusion formation per se.

PMID- 29180232
TI  - Areas of improvement in thromboprophylaxis of hospitalized medical patients.

PMID- 29180233
TI  - A non-invasive methodology for ATAA rupture risk estimation.
AB  - Ascending thoracic aortic aneurysms (ATAA) are a life-threatening pathology
      provoking an irreversible dilation with a high associated risk of aortic rupture
      or dissection and death of the patient. Rupture or dissection of ATAAs remains
      unpredictable and has been documented to occur at diameters less than 4.5 cm for
      nearly 60% of patients. Other factors than the aneurysm diameter may highly
      affect the predisposition to rupture. In order to have a better insight in
      rupture risk prediction, a bulge inflation bench was developed to test ATAAs
      samples collected on patients during surgical interventions. Preoperative dynamic
      CT scans on a cohort of 13 patients were analyzed to estimate volumetric and
      cross-sectional distensibility. A failure criteria based on in vitro ultimate
      stretch showed a significant correlation with the aortic membrane stiffness
      deduced from in vivo distensibility. These results reinforce the significance of
      stretch-based rupture criteria and their possible non-invasive prediction in
      clinical practice.

PMID- 29180234
TI  - Corrigendum to "Alterations of musculoskeletal models for a more accurate
      estimation of lower limb joint contact forces during normal gait: A systematic
      review" [J. Biomech. 63 (2017) 8-20].

PMID- 29180235
TI  - A proposed new instrument for detailed nutritional status assessment and a
      management protocol for malnourished patients.

PMID- 29180236
TI  - [Economic impact of etanercept and adalimumab biosimilars on hospitals scale
      covered by PharmAlp'Ain, a hospitals grouping of orders for health products].
AB  - OBJECTIVES: To evaluate the economic impact of future prescriptions of etanercept
      and adalimumab biosimilars at the territorial scale covered by PharmAlp'Ain, a
      hospitals grouping of orders for health products. METHODS: Determination of the
      number and status of patients (naive or in continuation of treatment) from the
      National Database "Datamart de Consommation Inter-Regimes" of health insurance,
      concerned by a dispensation in a pharmacy of etanercept or adalimumab in 2015.
      Calculation of potential savings in case of biosimilar requirements according to
      3 hypotheses: 63% (rate observed in a previous study) of initiations are treated
      with biosimiliaries and the others by princeps (H1); all initiations under
      biosimilars and continuation therapy with the princeps (H2) or all patients are
      treated with biosimilars (H3). RESULTS: The annual savings are estimated at
      237,000 ? with the H1 hypothesis. In the case of H2, the expected savings would
      be 376,200 ? per year. In the case of H3, savings for the community could reach
      almost 1,282,800 ? per year. CONCLUSION: The arrival of biosimilars allows
      significant savings for medicines market. According to the French recommendations
      in 2016, the expected savings are between the H1 and H2 hypothesis. The rate of
      penetration of biosimilars depends on many factors such as the involvement of
      health professionals, patient adherence, or health authority recommendations.

PMID- 29180237
TI  - [Haemorrhagic risk associated with skin cancer surgery: AMIF! (accept, manage,
      inform, follow-up)].

PMID- 29180238
TI  - Glucose homeostasis in the euryhaline crab Cytograpsus angulatus: Effects of the
      salinity in the amylase, maltase and sucrase activities in the hepatopancreas and
      in the carbohydrate reserves in different tissues.
AB  - We studied the existence, biochemical characteristics and response to different
      environmental salinities of amylase, maltase and sucrase activity in the
      intertidal euryhaline crab Cyrtograpsus angulatus (Dana, 1852) along with the
      response to distinct salinities of glycogen and free glucose content in storage
      organs. Amylase, maltase and sucrase activities were kept over a broad range of
      pH and temperature and exhibited Michaelis-Menten kinetics. Zymography showed the
      existence of two amylase forms in crabs exposed to 35 (osmoconformation) and low
      (6-10psu; hyper-regulation) or high (40psu) (hypo-regulation) salinities.
      Carbohydrases activity in the hepatopancreas and glycemia were not affected in
      crab exposed to different environmental salinities. In 6 and 40psu, the glycogen
      content in anterior gills was lower than in 35psu. In 6, 10 and 40psu, glycogen
      concentration in hepatopancreas, muscle and posterior gills were similar to that
      in 35psu. Free glucose concentration in chela muscle was higher in 6 and 40psu
      than in 35psu. The existence and biochemical characteristics of carbohydrases
      activity and the adjustments in concentration of glycogen in anterior gills and
      free glucose in chela muscle suggests the ability to perform complete hydrolysis
      of glycogenic substrates and to keep glucose homeostasis in relation to
      acclimation to different salinity conditions.

PMID- 29180239
TI  - Comparative biochemistry of cytochrome c oxidase in animals.
AB  - Cytochrome c oxidase (COX), the terminal enzyme of the electron transport system,
      is central to aerobic metabolism of animals. Many aspects of its structure and
      function are highly conserved, yet, paradoxically, it is also an important model
      for studying the evolution of the metabolic phenotype. In this review, part of a
      special issue honouring Peter Hochachka, we consider the biology of COX from the
      perspective of comparative and evolutionary biochemistry. The approach is to
      consider what is known about the enzyme in the context of conventional
      biochemistry, but focus on how evolutionary researchers have used this background
      to explore the role of the enzyme in biochemical adaptation of animals. In
      synthesizing the conventional and evolutionary biochemistry, we hope to identify
      synergies and future research opportunities. COX represents a rare opportunity
      for researchers to design studies that span the breadth of biology: molecular
      genetics, protein biochemistry, enzymology, metabolic physiology, organismal
      performance, evolutionary biology, and phylogeography.

PMID- 29180240
TI  - The 2018 Marcus W. Feldman Prize in Theoretical Population Biology.

PMID- 29180241
TI  - Generation of semiquinone-[2Fe-2S]+ spin-coupled center at the Qo site of
      cytochrome bc1 in redox-poised, illuminated photosynthetic membranes from
      Rhodobacter capsulatus.
AB  - One of the less understood parts of the catalytic cycle of cytochrome bc1/b6f
      complexes is the mechanism of electronic bifurcation occurring within the
      hydroquinone oxidation site (Qo site). Several models describing this mechanism
      invoke a phenomenon of formation of an unstable semiquinone. Recent studies with
      isolated cytochrome bc1 or b6f revealed that a relatively stable semiquinone spin
      coupled to the reduced Rieske cluster (SQ-FeS) is generated at the Qo site during
      the oxidation of ubi- or plastohydroquinone analogs under conditions of
      continuous turnover. Here, we identified the EPR transition of SQ-FeS formed upon
      oxidation of ubihydroquinone in native photosynthetic membranes from purple
      bacterium Rhodobacter capsulatus. We observed a significant amount of SQ-FeS
      generated when the antimycin-inhibited enzyme experiences conditions of non
      equilibrium caused by the continuous light activation of the reaction center. We
      also noted that SQ-FeS cannot be detected under equilibrium redox titrations in
      dark. The non-equilibrium redox titrations of SQ-FeS indicate that this center
      has a higher apparent redox midpoint potential when compared to the redox
      midpoint potential of the quinone pool. This suggests that SQ-FeS is stabilized,
      which corroborates a recently proposed mechanism in which the SQ-FeS state is
      metastable and functions to safely hold electrons at the local energy minimum
      during the oxidation of ubihydroquinone and limits superoxide formation. Our
      results open new possibilities to study the formation and properties of this
      state in cytochromes bc under close to physiological conditions in which non
      equilibrium is attained by the light activation of bacterial reaction centers or
      photosystems.

PMID- 29180242
TI  - Cell-free DNA characteristics and chimerism analysis in patients after allogeneic
      cell transplantation.
AB  - : Cell-free DNA (cfDNA) isolated from plasma or serum has received increasing
      interest for diagnostic applications in pregnancy, solid tumors and solid organ
      transplantation. The reported clinical usefulness of cfDNA obtained from plasma
      or serum in patients undergoing allogeneic cell transplantation (alloHSCT) is
      scarce. OBJECTIVE: To analyze the potential clinical utility of cfDNA chimerism
      analysis after alloHSCT. DESIGN AND METHODS: A total of 196 samples obtained from
      110 patients were investigated for their chimeric status both in peripheral blood
      and plasma using standard PCR for microsatellite amplification. Plasma DNA size
      distribution was analyzed using capillary electrophoresis. RESULTS: The mean
      cfDNA concentration in the transplanted patients was 469ng/ml (range: 50
      10,700ng/ml). The size range of almost 80% of the analyzed fragments was between
      80 and 200bp. In 41 out of the 110 patients included in the study a mixture of
      donor and recipient plasma cfDNA was detected. There was a statistically
      significant difference in the percentage of plasma mixed chimerism between the
      patients without transplant related complications and the patients with either
      GvHD (p<0.05) or relapse (p<0.01). In those patients who showed improvement of
      GvHD also displayed a decrease in the observable percentage of recipient cfDNA
      during GvHD treatment. In patients without improvement or even with worsening of
      acute GvHD, stable or increasing levels of recipient cfDNA were detected.
      CONCLUSIONS: cfDNA in combination with peripheral blood and bone marrow cell
      chimerism analysis might improve its utility in the clinic in particular in those
      patients with clinical complications after alloHSCT.

PMID- 29180243
TI  - Investigating error-related processing in incarcerated adolescents with self
      report psychopathy measures.
AB  - Disparate results have been found in previous reports when incorporating both
      interview-based and self-report measures of psychopathic traits within the same
      sample, suggesting such assessments should not be used interchangeably. We
      previously found Total and Facet 4 scores from Hare's Psychopathy Checklist:
      Youth Version (PCL:YV) were negatively related to amplitude of the error-related
      positivity (Pe) event-related potential (ERP) component. Here, we investigated
      using the same previously published sample whether scores on four different self
      report measures of adolescent psychopathic traits (the Antisocial Process
      Screening Device [APSD], Child Psychopathy Scale [CPS], Inventory of Callous
      Unemotional Traits [ICU], and Youth Psychopathic Traits Inventory [YPI]) were
      similarly associated with reduced Pe amplitude. Unlike our previous results,
      adolescent self-report psychopathy scores were not associated with reduced Pe
      amplitude in multiple regression analyses. Results obtained in the current report
      support previous research observing incongruent findings when incorporating
      different assessment types within the same sample.

PMID- 29180244
TI  - Dual loss of p110delta PI3-kinase and SKAP (KNSTRN) expression leads to combined
      immunodeficiency and multisystem syndromic features.
AB  - BACKGROUND: We previously reported a novel syndrome characterized by combined
      immunodeficiency associated with severe developmental defects-subsequently known
      as Roifman-Chitayat syndrome (RCS; OMIM 613328). Linkage analysis identified 2
      disease-associated loci. OBJECTIVES: We sought to identify the genetic defect in
      these patients and characterize their immunologic cellular abnormalities.
      METHODS: Genetic, immunologic, protein, and cellular functional analyses were
      used to identify and characterize patient genetic deficiencies and aberrant
      patient cell behavior. RESULTS: Deleterious variants were found at both loci
      identified by linkage analysis: a homozygous stop codon in PI3-kinase p110delta
      (PIK3CD) and a homozygous frame shift mutation in SKAP (KNSTRN), both ablating
      protein expression. Patients with RCS display aberrant B-cell development,
      similar to p110delta-deficient mice, but also aberrant T-cell spreading, cell
      cell interaction, and migration. Patients also display significant developmental
      abnormalities not seen in p110delta knockouts (eg, optic nerve atrophy and
      skeletal anomalies) that we ascribe to loss of SKAP. Aberrant SKAP expression can
      prolong anaphase and this may contribute to developmental defects. However, we
      also identified microtubule-associated protein 4 microtubule-binding protein as a
      novel SKAP-binding partner and show that it undergoes relocalization in patient T
      cells, with associated areas of aberrant microtubule hyperstabilization, likely
      contributing not only to the altered properties of RCS lymphoid cells but also to
      developmental defects. CONCLUSIONS: The complex RCS presentation, with combined
      developmental and immunologic defects, is associated with a combined deficiency
      of 2 genes products, PI3-kinase p110delta and SKAP, both of which appear to play
      a significant role in the disease.

PMID- 29180245
TI  - The detection of ACLSV and ASPV in pear plants by RT-LAMP assays.
AB  - A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay
      was developed for the detection of Apple chlorotic leaf spot virus (ACLSV) and
      Apple stem pitting virus (ASPV), two important viruses frequently occurring in
      pear trees. A set of four RT-LAMP primers designed based on the highly conserved
      region of each CP gene of the two viruses showed high specificity and feasibility
      for ACLSV and ASPV detections. The RT-LAMP assays for ACLSV and ASPV in pear
      samples were 104 and 103 times more sensitive than that of conventional RT-PCR
      assays. The RT-LAMP under optimal reaction condition was subsequently utilized in
      the detection of the two viruses in-vitro cultures of pear and field pear
      samples. This study provides a rapid and sensitive tool to determine the
      infection statues of the two viruses in pear certification program.

PMID- 29180246
TI  - The immunohistochemical expression and potential prognostic value of HDAC6 and AR
      in invasive breast cancer.
AB  - Previous studies have investigated the role of histone deacetylase 6 (HDAC6) in
      the regulation of androgen receptor (AR) in prostate cancer; however, the role of
      HDAC6 has not yet been clearly identified in breast cancer. The aim of this study
      was to examine the expression of HDAC6 and AR, determine the correlation between
      HDAC6 and AR, and assess the prognostic value of HDAC6 and AR in breast cancer. A
      total of 228 cases of invasive breast cancer were randomly selected. The
      expression of HDAC6 and AR was analyzed by immunohistochemistry. chi2 Tests were
      performed to determine the association between conventional clinicopathological
      factors and HDAC6, AR, and HDAC6/AR co-expression. Spearman correlation methods
      were performed to determine the correlation between HDAC6 and AR, and Kaplan
      Meier analyses were performed to determine the prognostic impact of HDAC6, AR and
      HDAC6/AR co-expression; 58.8% (134/228) patients exhibited high expression of
      HDAC6. High HDAC6 expression was significantly associated with high histologic
      grade (G3) (P<.001) and p53 overexpression (P=.002). HDAC6 and AR expression
      levels were significantly associated (r=0.382, P<.01). In estrogen receptor (ER)
      negative samples, high expression of HDAC6 was more common in the AR+ groups
      (P<.001) and correlated with high histologic grade (G3) (P=.009), as well as
      higher HER2 (P=.006) and p53 levels (P=.012). Higher expression of AR and HDAC6
      and HDAC6/AR co-expression had a worse clinical prognosis. The expression levels
      of HDAC6 and AR are correlated in breast cancer; moreover, HDAC6 and AR have
      prognostic value in predicting the overall survival (OS) of ER-negative breast
      cancer patients.

PMID- 29180247
TI  - Fewer seniors from United States allopathic medical schools are filling pathology
      residency positions in the Main Residency Match, 2008-2017.
AB  - Some pathologists have observed that fewer trainees from US medical schools are
      entering pathology residency. This trend was measured and further explored using
      Main Residency Match (MRM) data from 2008 to 2017, obtained from the National
      Resident Matching Program (NRMP). Over the past decade, there was an increase of
      93 (508 in 2008 versus 601 in 2017, an 18.3% increase) pathology positions
      offered in the MRM. However, the proportion of pathology residency positions
      filled in the MRM which were taken by trainees from US medical schools decreased
      from 77.7% to 50.1% over this timespan. This was primarily due to fewer seniors
      from US allopathic medical schools filling pathology positions in the MRM (298 in
      2008 versus 216 in 2017, a 27.5% decrease). Compared to 14 other medical
      specialties, pathology had the largest decline in the proportion of residency
      positions filled in the MRM which were taken by seniors from US allopathic
      medical schools (63.8% in 2008 versus 39.6% in 2017). Furthermore, pathology now
      has the lowest percentage of residency positions filled in the MRM, which were
      taken by seniors from US allopathic medical schools. The primary reason for this
      decline was because fewer seniors from US allopathic medical schools participated
      in the MRM for pathology positions (326 in 2008 versus 232 in 2017, a 28.8%
      decrease); however, the underlying reasons for this decline are unknown. In
      conclusion, over the past decade, substantially fewer seniors from US allopathic
      medical schools sought/filled pathology residency positions in the MRM. These
      findings are relevant for pathology residency recruitment, especially in the
      context of a projected decline in US pathologist workforce.

PMID- 29180248
TI  - Transient monoclonal gammopathy induced by Candida fungemia.
AB  - A 41-year-old woman was admitted for Candida fungemia. On hospital day 4, a
      routine complete blood count and peripheral smear showed circulating plasma
      cells. Initial workup showed an M-component on serum protein electrophoresis with
      6% lambda-predominate plasma cells by flow cytometry. The patient was treated
      with intravenous antifungal therapy. Her 6-month follow-up laboratory evaluation
      revealed resolution of the M-component and only rare polyclonal plasma cells in
      peripheral blood by flow cytometry. This case illustrates that transient
      monoclonal gammopathy can be induced by fungal infection. It is important to
      exclude a plasma cell neoplasm or a B-cell lymphoma and to follow the patient
      until resolution of abnormal findings.

PMID- 29180249
TI  - Tumor necrosis in radical prostatectomies with high-grade prostate cancer is
      associated with multiple poor prognostic features and a high prevalence of
      residual disease.
AB  - The Gleason grading system and the recently defined Grade Groups are strong, well
      established predictors of outcome in prostate cancer. Each Gleason score,
      however, is the result of a sum of categories (Gleason patterns or GPs) that are
      intrinsically heterogeneous, as each individual pattern encompasses several tumor
      morphologies. Although the prognostic value of specific morphologic components of
      GP4 has recently been demonstrated, the significance of the different patterns of
      GP5 is largely unknown. We reviewed 344 consecutive prostatectomies performed at
      the Hospital of the University of Illinois at Chicago between 2011 and 2016 and
      selected 56 cases with primary or secondary GP5 with archival material available
      for review. Subsequently, we sorted the cases according to the presence or
      absence of tumor necrosis in invasive adenocarcinoma GP5-designated G5 (+N) and
      G5 (-N), respectively-for comparison of histopathologic and clinical
      characteristics. The GP5 (+N) group demonstrated higher prevalence of biochemical
      recurrence (P=.0006) and seminal vesicle invasion (P=.02), with a trend toward a
      higher frequency of lymph node metastases (P=.07) and multifocal surgical margin
      involvement (P=.09). Also, G5 (+N) patients showed higher preoperative prostate
      specific antigen values (P=.005) and a larger percentage of submitted tissue
      involved by tumor (P<.0001). Our results show that GP5 with tumor necrosis is
      associated with poor prognostic histopathologic features and high rates of
      residual disease after prostatectomy.

PMID- 29180250
TI  - High interlaboratory and interobserver agreement of somatostatin receptor
      immunohistochemical determination and correlation with response to somatostatin
      analogs.
AB  - Monoclonal antibodies to somatostatin receptors 2A (SSTR2A, UMB-1) and 5 (SSTR5,
      UMB-4) were reported to be highly reliable for immunohistochemical detection of
      these receptors in neuroendocrine neoplasms. However, the standardization of
      either the immunohistochemical procedure and the methods of evaluation has yet to
      be established. Fifty-two tissues from 38 patients with neuroendocrine neoplasm
      were retrieved from 2 institutions in Italy and Japan. The tissues were
      immunostained using 3 staining methodologies: 1 automated and 2 manual protocols
      from the Italian and Japanese institutions. The slides were independently
      evaluated by 3 observers (2 experienced pathologists and 1 medical student) using
      3 scoring systems (Volante-Score, HER2-Score, and H-Score). The scores obtained
      from the staining methods were highly correlated with each other (r>0.85,
      P<.0001). Especially, the Volante- and HER2-Scores were highly concordant
      (r>=0.95, P<=.0001). Very high interobserver agreement was obtained irrespective
      of the method used and the experience of the evaluator, with the best concordance
      obtained by experienced pathologists evaluating automated system-stained slides
      (SSTR2A, r>0.97; SSTR5, r>0.96). HER2- and H-Scores were reliable to represent
      the characteristics of the patients. SSTR2A expression evaluated by the HER2
      Score was significantly associated with clinical efficacy to somatostatin analogs
      (P=.04). SSTRs determination is an easily standardizable tool in different
      laboratories and is highly reproducible irrespective of the method of evaluation
      used. Given the positive association with clinical efficacy to somatostatin
      analogs, as well as the simple and widespread use, HER2-Score can be proposed as
      a standard evaluation procedure of SSTR2A and SSTR5 expression in neuroendocrine
      neoplasms.

PMID- 29180251
TI  - Renal cell carcinoma with angioleiomyoma-like stroma and clear cell papillary
      renal cell carcinoma: exploring SDHB protein immunohistochemistry and the
      relationship to tuberous sclerosis complex.
AB  - Renal cell carcinoma (RCC) with angioleiomyoma-like stroma appears to be
      molecularly distinct from clear cell RCC; however, its relationship to clear cell
      papillary RCC remains debated. Recent studies have found that similar tumors
      sometimes occur in patients with tuberous sclerosis complex (TSC), of which 1
      study found unexpectedly negative succinate dehydrogenase B (SDHB)
      immunostaining. We evaluated immunohistochemistry for SDHB in 12 apparently
      sporadic RCCs with angioleiomyoma-like stroma and correlated with clinical
      information for stigmata of TSC. Tumors were compared with a group of 16 clear
      cell papillary RCCs and 6 unclassified tumors with prominent stroma. With the
      exception of 1 unclassified tumor, all exhibited at least focal cytoplasmic
      staining for SDHB protein, often requiring high magnification and better
      appreciated with increased antibody concentration. Detailed history information
      was available for 9 of 11 patients with smooth muscle-rich tumors, revealing no
      stigmata of undiagnosed TSC. Electron microscopy performed on 1 of these tumors
      revealed mitochondria to be very sparse, potentially accounting for the weak
      immunohistochemical labeling for SDHB protein. Weak SDHB immunostaining may
      represent another shared feature of RCC with angioleiomyoma-like stroma and clear
      cell papillary RCC, likely due to sparse mitochondria, strengthening the possible
      relationship of these entities. Although smooth muscle-rich tumors have been
      recently reported in patients with TSC, absence of staining in tumors with this
      pattern may not be specific for TSC. In tumors with pale or clear cytoplasm,
      immunohistochemical staining for SDHB should be interpreted with caution as
      evidence of abnormality in the SDH pathway.

PMID- 29180252
TI  - Distinction of intrahepatic metastasis from multicentric carcinogenesis in
      multifocal hepatocellular carcinoma using molecular alterations.
AB  - Patients with hepatocellular carcinoma (HCC) frequently have multiple
      anatomically distinct tumors. In these patients, multifocal HCC could represent
      intrahepatic metastases (IMs) of a single cancer or multicentric carcinogenesis
      (MC) with multiple independent neoplasms. To determine the frequency and clinical
      implications of these 2 possibilities, we performed histological and molecular
      analysis of 70 anatomically distinct HCCs from 24 patients. We assayed mutations
      in the TERT promoter region by Sanger sequencing and used next-generation
      sequencing to analyze the entire coding regions of 7 well-characterized HCC
      driver genes-based on shared or discordant mutations in these genes, we
      classified the HCCs in each patient as IM, MC, or indeterminate. Mutations in the
      TERT promoter were the most common alteration in our cohort, present in 71% of
      tumors analyzed. Mutations in the remaining genes occurred in less than 20% of
      analyzed tumors. We were able to determine the relatedness in 58% of the patients
      analyzed: MC occurred in 41% of patients, with 33% with exclusively MC and 8%
      with both MC and IM. IM occurred exclusively in 17% of patients, whereas the
      remainder were indeterminate. This study highlights the utility of molecular
      analyses to determine relatedness in multifocal HCC; however, targeted sequencing
      can only resolve this distinction in approximately 60% of patients with
      multifocal HCC.

PMID- 29180253
TI  - Pathology and radiology correlation of idiopathic interstitial pneumonias.
AB  - By nature, idiopathic interstitial pneumonias have been diagnosed in a
      multidisciplinary manner. As classifications have been subject to significant
      refinement over the last decade, the importance of correlating clinical,
      radiologic, and pathologic information to arrive at a diagnosis, which will
      predict prognosis in any given patient, has become increasingly recognized. In
      2013, the American Thoracic Society and European Respiratory Society updated the
      idiopathic interstitial pneumonias classification scheme, addressing the most
      recent updates in the field. The purpose of this review is to highlight the
      correlations between radiologic and pathologic findings in idiopathic
      interstitial pneumonias while using updated classification schemes and naming
      conventions.

PMID- 29180254
TI  - Reclaiming hijacked phagosomes: Hybrid nano-in-micro encapsulated MIAP peptide
      ensures host directed therapy by specifically augmenting phagosome-maturation and
      apoptosis in TB infected macrophage cells.
AB  - TB-Superbugs have emerged as one of the most challenging global health threat due
      to the decrease in effectiveness of conventional antibiotics. Meanwhile, Host
      defense peptides (HDP) have evolved as an alternative to classical therapeutics
      with lesser susceptibility of resistance. We describe the potential of nano
      encapsulated synthetic Magainin-I analog peptide (MIAP) as Host Directed Therapy
      against TB. Micron-sized inhalable platform "Porous Nanoparticle Aggregates
      Particles (PNAP)" with nano-scale physiognomies were developed to improve the
      delivery of MIAP-peptide to the lungs and enhance its stability. This particle
      engineering enabled more control over aerodynamic characteristics and bioactive
      release. Antimicrobial and mechanistic studies were carried out against virulent
      H37Rv TB bacteria. These MIAP-PNAP nano-assemblies demonstrated dose and time
      dependent antibacterial action against virulent M.tb for at least 96 h, with up
      to ~3.03-log CFU reduction in numbers of viable bacteria compared to untreated
      group. These MIAP-PNAP at concentration of 50 MUM and above showed significant
      antibacterial effects on M.tb after 48-96 h of incubation. Mechanistically, MIAP
      nano-formulation enhanced host defense mechanism by averting bacteria-induced
      inhibition of phagosomal-lysosome fusion (Lysostracker) and apoptosis (Annexin
      FITC) as shown by confocal microscopy and flow-cytometry. Encapsulated MIAP may
      serve for adjunctive host-directed TB therapy which may also synergizes the
      efficacy of standard anti-TB drugs.

PMID- 29180255
TI  - Nanoparticle-loaded hydrogels as a pathway for enzyme-triggered drug release in
      ophthalmic applications.
AB  - The aim of this study was to develop nanoparticle loaded hydrogel based contact
      lenses that could be used for ocular drug delivery. Two potential contact lens
      platforms for controlled ophthalmic drug delivery were developed by incorporating
      chitosan-poly (acrylic acid) nanoparticles into polyvinyl alcohol (PVA) hydrogels
      and in-situ gelled nanoparticles and cellulose nanocrystals (CNC) in PVA lenses.
      The nanoparticles were shown to disintegrate in a physiological 0.2 mM
      concentration of lysozyme resulting from the hydrolysis of the chitosan chains by
      lysozyme. An extended release over a 28-h period was demonstrated once the
      nanoparticles had been integrated into the composite lenses, with nanoparticle
      CNC PVA lenses showing even greater potential for extended release. The platform
      shows great promise in developing enzyme-triggered ocular drug delivery systems.

PMID- 29180256
TI  - Effects of solvents on skin absorption of nonvolatile lipophilic and polar
      solutes under finite dose conditions.
AB  - The effects of solvents upon the deposition of a moderately lipophilic solute on
      skin and skin permeation were investigated previously. The present study was a
      continuing effort to investigate the effects of solvents on finite dose skin
      absorption of nonvolatile lipophilic and polar solutes and examine the
      relationships between solute physicochemical properties, solvent effects, and
      skin absorption of these solutes after solvent deposition. Skin permeation
      experiments under the finite dose conditions were conducted with model solutes
      (corticosterone, urea, mannitol, glycerol, triamcinolone acetonide, and
      estradiol) and model solvents (ethanol, butanol, water, and propylene glycol)
      using Franz diffusion cells and human epidermal membrane. Urea showed
      unexpectedly high skin permeation under the finite dose conditions compared to
      the other solutes based on their skin permeability coefficients (obtained under
      infinite dose condition). The influences of the solvents on solute permeation
      suggest that these solvents did not act solely as a vehicle for spreading the
      solutes during solvent deposition. In the testing of skin permeation mechanisms,
      model analyses indicated a correlation between solute permeation and their
      molecular weights and solubilities, suggesting that the solute permeation
      mechanism with the volatile solvent was related to solute dissolution on the skin
      surface and its diffusion across the skin.

PMID- 29180257
TI  - Insights on animal models to investigate inhalation therapy: Relevance for
      biotherapeutics.
AB  - Acute and chronic respiratory diseases account for major causes of illness and
      deaths worldwide. Recent developments of biotherapeutics opened a new era in the
      treatment and management of patients with respiratory diseases. When considering
      the delivery of therapeutics, the inhaled route offers great promises with a
      direct, non-invasive access to the diseased organ and has already proven
      efficient for several molecules. To assist in the future development of inhaled
      biotherapeutics, experimental models are crucial to assess lung deposition,
      pharmacokinetics, pharmacodynamics and safety. This review describes the animal
      models used in pulmonary research for aerosol drug delivery, highlighting their
      advantages and limitations for inhaled biologics. Overall, non-clinical species
      must be selected with relevant scientific arguments while taking into account
      their complexities and interspecies differences, to help in the development of
      inhaled medicines and ensure their successful transposition in the clinics.

PMID- 29180258
TI  - Ten simple rules for neuroimaging meta-analysis.
AB  - Neuroimaging has evolved into a widely used method to investigate the functional
      neuroanatomy, brain-behaviour relationships, and pathophysiology of brain
      disorders, yielding a literature of more than 30,000 papers. With such an
      explosion of data, it is increasingly difficult to sift through the literature
      and distinguish spurious from replicable findings. Furthermore, due to the large
      number of studies, it is challenging to keep track of the wealth of findings. A
      variety of meta-analytical methods (coordinate-based and image-based) have been
      developed to help summarise and integrate the vast amount of data arising from
      neuroimaging studies. However, the field lacks specific guidelines for the
      conduct of such meta-analyses. Based on our combined experience, we propose best
      practice recommendations that researchers from multiple disciplines may find
      helpful. In addition, we provide specific guidelines and a checklist that will
      hopefully improve the transparency, traceability, replicability and reporting of
      meta-analytical results of neuroimaging data.

PMID- 29180259
TI  - Post-Operative Cognitive Dysfunction: An exploration of the inflammatory
      hypothesis and novel therapies.
AB  - Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with
      significant clinical, social and financial impacts for patients and their
      communities. The underlying pathophysiology is becoming increasingly understood,
      with the role of neuroinflammation and oxidative stress secondary to surgery and
      anaesthesia strongly implicated. This review aims to describe the putative
      mechanisms by which surgery-induced inflammation produces cognitive sequelae,
      with a focus on identifying potential novel therapies based upon their ability to
      modify these pathways.

PMID- 29180260
TI  - A novel de novo activating mutation in STAT3 identified in a patient with common
      variable immunodeficiency (CVID).
AB  - Common variable immunodeficiency (CVID) is characterised by repeated infection
      associated with primary acquired hypogammaglobulinemia. CVID frequently has a
      complex aetiology but, in certain cases, it has a monogenic cause. Recently,
      variants within the gene encoding the transcription factor STAT3 were implicated
      in monogenic CVID. Here, we describe a patient presenting with symptoms
      synonymous with CVID, who displayed reduced levels of IgG and IgA, repeated viral
      infections and multiple additional co-morbidities. Whole-exome sequencing
      revealed a de novo novel missense mutation in the coiled-coil domain of STAT3
      (c.870A>T; p.K290N). Accordingly, the K290N variant of STAT3 was generated, and a
      STAT3 responsive dual-luciferase reporter assay revealed that the variant
      strongly enhances STAT3 transcriptional activity both under basal and stimulated
      (with IL-6) conditions. Overall, these data complement earlier studies in which
      CVID-associated STAT3 mutations are predicted to enhance transcriptional
      activity, suggesting that such patients may respond favourably to IL-6 receptor
      antagonists (e.g. tocilizumab).

PMID- 29180261
TI  - Optimal choice of k-mer in composition vector method for genome sequence
      comparison.
AB  - Several proteins and genes are members of families that share a public
      evolutionary. In order to outline the evolutionary relationships and to recognize
      conserved patterns, sequence comparison becomes an emerging process. The current
      work investigates critically the k-mer role in composition vector method for
      comparing genome sequences. Generally, composition vector methods using k-mer are
      applied under choice of different value of k to compare genome sequences. For
      some values of k, results are satisfactory, but for other values of k, results
      are unsatisfactory. Standard composition vector method is carried out in the
      proposed work using 3-mer string length. In addition, special type of information
      based similarity index is used as a distance measure. It establishes that use of
      3-mer and information based similarity index provide satisfactory results
      especially for comparison of whole genome sequences in all cases. These
      selections provide a sort of unified approach towards comparison of genome
      sequences.

PMID- 29180262
TI  - Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to
      hypertension-induced cardiac hypertrophy.
AB  - Cardiac hypertrophy is a major characteristic of early-stage hypertension-related
      heart failure. We have found that the insulin-like growth factor receptor II (IGF
      IIR) signaling was critical for hypertensive angiotensin II-induced cardiomyocyte
      hypertrophy and apoptosis. Moreover, this IGF-IIR signaling was elegantly
      modulated by the heat shock transcription factors (HSFs) during heart failure.
      However, the detailed mechanism by which HSFs regulates IGF-IIR during
      hypertension-induced cardiac hypertrophy remains elusive. In this study, we found
      that heat shock transcription factor 2 (HSF2) activated IGF-IIR to induce cardiac
      hypertrophy for hypertension-induced heart failure. The transcriptional activity
      of HSF2 appeared to be primarily mediated by SUMOylation via conjugation with
      small ubiquitin-like modifier-1 (SUMO-1). The SUMOylation of HSF2 was severely
      attenuated by MEL18 (also known as polycomb group ring finger 2 or PCGF2) in the
      heart of spontaneously hypertensive rats (SHR). Inhibition of HSF2 SUMOylation
      severely induced cardiac hypertrophy via IGF-IIR-mediated signaling in
      hypertensive rats. Angiotensin II receptor type I blocker (ARB) treatment in
      spontaneously hypertensive rats restored HSF2 SUMOylation and alleviated the
      cardiac defects. Thus, our study uncovered a novel MEL18-SUMO-1-HSF2-IGF-IIR
      pathway in the heart that profoundly influences cardiac hypertrophy for
      hypertension-induced heart failure.

PMID- 29180263
TI  - Polypill, hypertension and medication adherence: The solution strategy?
AB  - INTRODUCTION: Hypertension is an important global health challenge and a leading
      preventable risk factor for premature death and disability worldwide. In current
      cardiology practice, the main obstacles in the management of patients affected by
      hypertension are comorbidities and poor adherence to pharmacological treatments.
      The World Health Organization has recently highlighted increased adherence as a
      key development need for reducing cardiovascular disease. METHODS: Principal
      observational and clinical trial data regarding adherence, reductions in
      cardiovascular risk and safety of the polypill approach are summarized and
      reviewed. CONCLUSIONS: The polypill approach has been conclusively shown to
      increase adherence relative to usual care in all cardiovascular patients,
      furthermore, concomitant risk factor reductions have also been suggested. To
      date, the use of polypill could represent a solution strategy in patients
      affected by hypertension, comorbidities and non-adherence even though further
      studies, especially in the real-world settings, are needed in order to better
      understand its role in clinical practice.

PMID- 29180264
TI  - Impact of persistent ST elevation on outcome in patients with Takotsubo syndrome.
      Results from the GErman Italian STress Cardiomyopathy (GEIST) registry.
AB  - BACKGROUND: Potential predictors of clinical complications of Takotsubo syndrome
      (TTS) are poorly known. Persistent ST-segment elevation (PSTE) may have an impact
      on outcome similar as previously reported in acute coronary syndrome. The aim of
      this study was to assess the prevalence and prognostic relevance of PSTE in
      patients with TTS. METHODS: Two-hundred-sixty-nine consecutive patients were
      enrolled in an international multicenter registry. PSTE was defined as the
      documentation of ST-elevation at least for the first 48h of hospitalization. Long
      term mortality was evaluated in median 1.9years after the acute event. RESULTS:
      PSTE was found in 52 TTS patients (19%). Patients with PSTE were characterized by
      higher admission levels of troponin-I (23+/-12 vs 8+/-49ng/L, p<0.001),
      experienced a longer hospitalization (10+/-5 vs 8+/-3days, p=0.02) and a higher
      rate of in-hospital complications (31% vs 17% p=0.03). At multivariate analysis
      including PSTE, age, male sex, admission ejection fraction, PSTE (odds ratio [OR]
      4.2; 95% confidence interval [CI] 1.4-13; p=0.01), age (OR 1.05; 95%CI 1.00-1.10;
      p=0.03) and admission ejection fraction (OR 0.93; 95%CI 0.87-0.99; p=0.02) were
      independent predictors of in-hospital complications. At long-term follow-up no
      significant differences in terms of mortality were observed between patients with
      and without PSTE (19% vs 15%; p=0.5). However, PSTE was a predictor of major
      cardiac adverse events (MACE) at follow-up (HR 2.32, 95% CI 1.02-5.31, p 0.045).
      CONCLUSIONS: In TTS patients, PSTE is a common finding, represents an independent
      predictor of in-hospital complications and could be associated with MACE at
      follow-up.

PMID- 29180265
TI  - Corrigendum to "Physiologic mechanism of discordance between instantaneous wave
      free ratio and fractional flow reserve: Insight from 13N-ammonium positron
      emission tomography" [Int. J. Cardiol. 243 (2017) 91-94].

PMID- 29180266
TI  - Heart, kidney and FGF23: Les liaisons dangereuses.

PMID- 29180268
TI  - Takayasu arteritis in young women with acute ischemic heart disease: Time to
      shift from anecdote to clinical practice?

PMID- 29180267
TI  - Cardiac arrest and Brugada syndrome: Is drug-induced type 1 ECG pattern always a
      marker of low risk?
AB  - BACKGROUND: Patients diagnosed as affected by Brugada syndrome (BrS) on the basis
      of a drug-induced type 1 ECG pattern (type1) are regarded as at low risk for
      cardiac arrest. We tested whether this assumption matches reality. METHODS: The
      study population included 26 patients from our group and 217 patients from three
      studies published between 2002 and 2013, all of them with aborted cardiac arrest
      (ACA) and in whom a previously unrecognized type1 (spontaneous or drug-induced)
      was discovered after the event, thus leading to the diagnosis of BrS. RESULTS:
      Among our 26 patients, a drug-induced type1 was detected in 11 (42%) and only
      1/11 showed a spontaneous pattern during follow-up; of 6 patients with syncope
      before ACA, 4 (67%) had only a drug-induced pattern. ICD shocks rates were
      similar in both spontaneous and drug-induced groups (57% and 45%). Early on, year
      2002, the percentage of drug-induced type1 after ACA was much lower (14%) and has
      progressively increased to approximately 50%. CONCLUSIONS: If drug-induced type1
      carries low arrhythmic risk, it should seldom be the only marker for BrS after an
      ACA. In studies on patients after an unexpected ACA, a drug-induced type1 leads
      to the diagnosis of BrS more often than anticipated. This contrasts with
      prospective studies focusing on patients already diagnosed as BrS and which
      consider drug-induced type1 as a marker of low risk. Contrary to current views,
      it is possible that not all patients with a drug-induced BrS type1 are at low
      risk of future events.

PMID- 29180270
TI  - The Colombian peace deal and its impact on the evolution of tropical diseases
      agents.

PMID- 29180269
TI  - Dysregulation of antioxidant responses in patients diagnosed with concomitant
      Primary Sclerosing Cholangitis/Inflammatory Bowel Disease.
AB  - OBJECTIVE: Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver
      disease that is characterized by severe peri-biliary tract inflammation and
      fibrosis, elevated oxidative stress and hepatocellular injury. A hallmark of PSC
      patients is the concurrent diagnosis of Inflammatory Bowel Disease occurring in
      approximately 70%-80% of PSC patients (PSC/IBD). The objective of this study was
      to determine the impact of end stage PSC/IBD on cellular antioxidant responses
      and the formation of protein carbonylation. METHODS: Using hepatic tissue and
      whole cell extracts isolated from age-matched healthy humans and patients
      diagnosed with end stage PSC/IBD, overall inflammation, oxidative stress, and
      protein carbonylation were assessed by Western blotting, and
      immunohistochemistry. RESULTS: Increased immunohistochemical staining for CD3+
      (lymphocyte), CD68 (Kupffer cell) and myeloperoxidase (neutrophil) colocalized
      with the extensive Picrosirius red stained fibrosis confirming the inflammatory
      aspect of PSC. Importantly, the increased inflammation also colocalized with
      elevated periportal post-translational modification by the reactive aldehydes 4
      HNE, MDA and acrolein. 4-HNE, MDA and acrolein IHC all displayed a significant
      component in hepatocytes adjacent to fibrotic regions. Furthermore, acrolein was
      also elevated within the nuclei of periportal inflammatory cells whereas MDA
      staining was increased in hepatocytes across the lobule. Prussian Blue staining,
      when compared to the positive controls (ALD, NASH), did not display any evidence
      of iron accumulation in PSC/IBD livers. Western analysis of PSC/IBD anti-oxidant
      responses revealed elevated expression of SOD2, GSTpi as well as upregulation of
      Akt Ser473 phosphorylation. In contrast, expression of GSTMU, GSTA4, catalase,
      Gpx1 and Hsp70 were suppressed. These data were further supported by a
      significant decrease in measured GST activity. Dysregulation of anti-oxidant
      responses in the periportal region of the liver was supported by elevated SOD2
      and GSTpi IHC signals in periportal hepatocytes and cholangiocytes. Expression of
      the Nrf2-regulated proteins HO-1, NAD(P)H quinone reductase (NQO1) and Gpx1 was
      primarily localized to macrophages. In contrast, catalase staining decreased
      within periportal hepatocytes and was not evident within cholangiocytes.
      CONCLUSIONS: Results herein provide additional evidence that cholestasis induces
      significant increases in periportal oxidative stress and suggest that there are
      significant differences in the cellular and subcellular generation of reactive
      aldehydes formed during cholestatic liver injury. Furthermore, these data suggest
      that anti-oxidant responses are dysregulated during end-stage PSC/IBD supporting
      pathological data. This work was funded by NIH5R37AA009300-22 D.R.P.

PMID- 29180271
TI  - Reconstructive techniques for revision and limb salvage surgery in persons with
      haemophilia.
AB  - Haemophilia is an inherited haemorrhagic disease characterized by the lack of
      coagulative factors associated nowadays mostly to musculoskeletal complications,
      particularly severe secondary arthritis in specific joints. Recurrent traumatic
      or spontaneous joint bleeding, induce severe arthropathy at a young age that can
      be treated only by joint replacement. Total knee or hip arthroplasty in young
      subjects may fail earlier due to wear or infections and in the haemophilic
      population, this means bone loss, pseudo tumours and the need of revision or even
      limb salvage surgery. Modern modular implants and the use of bone graft enriched
      by tissue engineering techniques such as a concentration of autologous
      mesenchymal cells or PRP may be helpful to compensate all bone loss and anatomic
      alterations due to failures of orthopaedic implants. The authors present their
      experience with this type of surgery and their biological approach to these
      challenging cases.

PMID- 29180272
TI  - Combination of MALDI-TOF MS and PBP2' latex agglutination assay for rapid MRSA
      detection.
AB  - Sample preparation was optimized for MALDI-TOF MS directly from the selective
      enrichment broth to detect Staphylococcus aureus. A combination of MALDI-TOF MS
      and the PBP2' latex agglutination assay was applied for MRSA screening and
      evaluated on 255 clinical samples. MRSA colonisation can be reported already 18
      24h after sample collection.

PMID- 29180273
TI  - Evaluation of vitrification protocol of mouse ovarian tissue by effect of DNA
      methyltransferase-1 and paternal imprinted growth factor receptor-binding protein
      10 on signaling pathways.
AB  - Transplantation of cryopreserved ovarian tissue has been considered as a
      promising way of fertility preservation for women. however, this cryopreservation
      method is prone to post-resuscitation follicle proliferation and oocyte
      development stagnation, affecting late transplant survival. To evaluate current
      vitrification works, we investigated the critical pathway alternations in
      vitrified-warmed juvenile 10-day-old mouse ovary. We showed a significant
      decrease of protein kinase B (Akt) and Mitogen-activated protein kinase (Mapk)
      phosphorylation, during which serine/threonine kinases play central roles in
      coordinating follicle and oocyte development and stress response. Inhibition of
      Akt and Mapk activity were associated with one of the imprinted insulin pathway
      negative regulatory genes, Growth factor receptor-binding protein 10 (Grb10)
      which remarkably increased in vitrified-warmed juvenile mouse ovary than that of
      fresh group (p < 0.05). RNAi-induced Grb10 down-regulation reversed the decrease
      in Akt and Mapk phosphorylation. The increase of Grb10 expression was partially
      caused by the hyper-methylation of the promoter region, associated with the
      decrease of follicular DNA methyltransferase (Dnmt) 1 protein in different stages
      of vitrified-warmed group, compared to fresh group (p < 0.05). The mRNA and
      protein expression of Dnmt1 in ovary of vitrified-warmed juvenile mouse were
      remarkably lower than those in fresh group (p < 0.05). Dnmt1 overexpression
      dramatically reversed Grb10 up-regulation and Akt and Mapk phosphorylation
      reduction. Taken together, our findings suggest that Grb10 expression might be
      helpful in evaluation of effectiveness of vitrification, and considered as a
      potential target for further vitrification protocols improvement in the future.

PMID- 29180274
TI  - Protocol for cryopreservation of the turbot parasite Philasterides dicentrarchi
      (Ciliophora, Scuticociliatia).
AB  - Philasterides dicentrarchi is a free-living marine ciliate that can become an
      endoparasite that causes a severe disease called scuticociliatosis in cultured
      fish. Long-term maintenance of this scuticociliate in the laboratory is currently
      only possible by subculture, with periodic passage in fish to maintain the
      virulence of the isolates. In this study, we developed and optimized a
      cryopreservation protocol similar to that used for the long-term storage of
      scuticociliates of the genus Miamiensis. The cryogenic medium comprised ATCC
      medium 1651 and a combination of 11% dimethylsulfoxide and 5% glycerol. We have
      verified that the most important factor ensuring the efficiency of the
      cryopreservation procedure is the growth phase of the culture, and that ciliates
      should be cryopreserved at the stationary phase (around the sixth day of
      culture). The cryopreservation protocol described here can be used for all
      strains of P. dicentrarchi as well as commercial strains of Miamiensis and
      enables the virulence of the strains to be maintained. Finally, this
      cryopreservation protocol has been shown to be more effective than others
      routinely applied to scuticociliates, yielding a higher survival rate with a
      lower initial concentration of ciliates. The results obtained indicate that the
      cropreservation protocol enables the long-term storage of scuticociliate
      parasites while maintaining the virulence of the isolates. The protocol is
      therefore suitable for use in vaccine production and related studies.

PMID- 29180275
TI  - [Exhaustivity and critical tone of the news in print media reporting medical
      innovations].
AB  - OBJECTIVE: To quantify how exhaustive and critical were stories reporting medical
      innovations published in print media and to analyze the characteristics that may
      be related. METHOD: Content analysis of the newspapers stories related to the
      discovery, introduction or improvement of a medical innovation through a
      questionnaire with ten criteria that allows calculating an overall score of
      exhaustiveness. The critical view was also included. RESULTS: We analyzed 204
      newspapers stories that on average obtained a comprehensiveness score of 4.5.
      Were optimistic 70% of the stories. The most valued criteria were: level of
      detail of the explanation of the innovation and the correct differentiation
      between facts and opinions. While the worst-valued criteria were: disclosure of
      financial conflicts of interest and the quantification of harms. The variables
      author, length of the story and classification of the innovation were related to
      both the comprehensiveness score and the critical view. The comprehensiveness
      score was also related to the pathology, number of sources of information and the
      critical tone of the story, while the critical view was also related to the
      newspapers diffusion and the relevance of the news. CONCLUSIONS: The analyzed
      stories presented inaccuracies, biases or an excess of optimism (either
      intentional or involuntary). Some aspects of the stories discussed in more detail
      would provide solutions to many of the identified shortcomings.

PMID- 29180277
TI  - High prevalence of mcr-1, mcr-3 and mcr-5 in Escherichia coli derived from
      diseased pigs in Japan.

PMID- 29180276
TI  - Dalbavancin in the treatment of different gram-positive infections: a real-life
      experience.
AB  - Dalbavancin is a lipoglycopeptide with a very prolonged half-life enabling
      treatment with a single intravenous administration that has been approved to
      treat complicated skin and soft-tissue infections. Information on the efficacy
      and safety of dalbavancin in other situations is very scarce. This retrospective
      study included adult patients who received at least one dose of dalbavancin
      between 2016 and 2017 in 29 institutions in Spain. The primary objective was to
      report the use of dalbavancin in clinical practice, including its efficacy and
      tolerability. The potential impact of dalbavancin on reducing the length of
      hospital stay and hospital costs was also evaluated. A total of 69 patients
      received dalbavancin during the study period (58.0% male; median age 63.5 years).
      Dalbavancin was used to treat prosthetic joint infection (29.0%), acute bacterial
      skin and skin-structure infection (21.7%), osteomyelitis (17.4%) and catheter
      related bacteraemia (11.6%). These infections were mainly caused by
      Staphylococcus aureus (27 isolates), coagulase-negative staphylococci (24
      isolates) and Enterococcus spp. (11 isolates). All but two patients received
      previous antibiotics for a median of 18 days. Dalbavancin was administered for a
      median of 21 days (range 7-168 days), and concomitant antimicrobial therapy was
      prescribed to 25 patients (36.2%). The overall clinical success rate of
      dalbavancin was 84.1%. Adverse events, mainly mild in intensity, were reported in
      nine patients. Overall, dalbavancin was estimated to reduce hospitalisation by
      1160 days, with an estimated overall cost reduction of ?211 481 (?3064 per
      patient). Dalbavancin appears to be an effective therapy for many serious Gram
      positive infections.

PMID- 29180278
TI  - Higher versus standard amikacin single dose in emergency department patients with
      severe sepsis and septic shock: a randomised controlled trial.
AB  - Recent studies suggest that intensive care unit patients treated with amikacin
      frequently do not attain the desired pharmacokinetic/pharmacodynamic (PK/PD)
      target, i.e. peak amikacin concentration (Cpeak) to minimum inhibitory
      concentration (MIC) ratio of >=8, when a single dose of 15 mg/kg is used. No data
      are available for patients admitted to the emergency department (ED). The aim of
      this prospective randomised controlled study was to determine PK/PD target
      attainment in ED patients presenting with severe sepsis or septic shock treated
      with 15 mg/kg versus 25 mg/kg amikacin. Patients were randomly assigned to
      receive amikacin 25 mg/kg or 15 mg/kg. Amikacin Cpeak values were determined. The
      primary outcome was target attainment defined as Cpeak/MIC >= 8 both using EUCAST
      susceptibility breakpoints and actually documented MICs as denominator. A total
      of 104 patients were included. The EUCAST-based target was attained in 76% vs.
      40% of patients assigned to the 25 mg/kg vs. 15 mg/kg dose groups (P <0.0001).
      Target attainment using actual MICs (median of 2 mg/L, documented in 48 isolated
      Gram-negative pathogens) was achieved in 95% vs. 94% of patients in the 25 mg/kg
      vs. 15 mg/kg dose groups (P = 0.969). Risk factors associated with PK/PD target
      failure were identified in the multivariable analysis. At least 25 mg/kg amikacin
      as a single dose should be used in ED patients with severe sepsis and septic
      shock to attain the EUCAST-based PK/PD target. However, when using local
      epidemiology as denominator, 15 mg/kg appears to be sufficient.
      [ClinicalTrials.gov ID: NCT02365272.

PMID- 29180279
TI  - Impact of the colistin resistance gene mcr-1 on bacterial fitness.
AB  - A Klebsiella pneumoniae isolate harbouring a 217 kb IncHI2-type plasmid (pKP2442)
      encoding the colistin resistance gene mcr-1 was isolated from a leukaemia
      patient. pKP2442 was mobilised by intragenus and intergenus transconjugation from
      the clinical isolate to Escherichia coli J53 (transconjugation frequency 6.86 *
      10-8 +/- 5.57 * 10-8) and K. pneumoniae PRZ (transconjugation frequency 4.04 * 10
      8 +/- 3.03 * 10-8), respectively. Since acquisition of resistance determinants
      often results in a loss of fitness, the impact of mcr-1 on the fitness of E. coli
      and K. pneumoniae was investigated. Escherichia coli J53 and K. pneumoniae PRZ
      transformants harbouring the TOPO expression vector encoding mcr-1 displayed
      significantly decreased growth rates compared with isogenic parental strains and
      controls. In contrast, competitive growth experiments revealed equal growth rates
      between E. coli J53 pKP2442 transconjugants (TcpKP2442) and the parental strain,
      whereas K. pneumoniae PRZ TcpKP2442 showed significantly reduced growth rates
      compared with their parental strain (selection rate constant -1.62 +/- 0.49),
      indicating a decrease in fitness. Infection of A549 human lung epithelial cells
      with TcpKP2442 or mcr-1 transformants and controls revealed equal lactate
      dehydrogenase activities, indicating no significant impact of mcr-1 on
      cytotoxicity. Likewise, survival of Galleria mellonella larvae infected with mcr
      1-expressing strains and isogenic controls was similar. These data indicate that
      expression of mcr-1 is able to cause a fitness cost when encoded on expression
      vectors and that acquisition of natural plasmid-borne mcr-1 does not impair
      fitness in E. coli J53 but negatively influences growth rates in K. pneumoniae
      PRZ.

PMID- 29180280
TI  - Association between augmented renal clearance, antibiotic exposure and clinical
      outcome in critically ill septic patients receiving high doses of beta-lactams
      administered by continuous infusion: a prospective observational study.
AB  - This study assessed whether augmented renal clearance (ARC) impacts negatively on
      antibiotic concentrations and clinical outcomes in patients treated by high-dose
      beta-lactams administered continuously. Over a 9-month period, all critically ill
      patients without renal impairment treated by one of the monitored beta-lactams
      for a documented infection were eligible. During the first 3 days of antibiotic
      therapy, every patient underwent 24-h CLCr measurements and therapeutic drug
      monitoring. The main outcome was the rate of beta-lactam underdosing, defined as
      a free drug concentration <4 * MIC of the known pathogen. Secondary outcomes were
      rates of subexposure for beta-lactams and therapeutic failure. The performance of
      CLCr in predicting underdosing was assessed by a ROC curve, and multivariable
      logistic regression was performed to determine risk factors for subexposure and
      therapeutic failure. A total of 79 patients were included and 235 samples were
      analysed. The rate of underdosing<4*MIC was 12%, with a significant association
      with CLCr (P <0.0001). A threshold of CLCr >= 170 mL/min had a sensitivity and
      specificity of 0.93 (95% CI 0.77-0.99) and 0.65 (95% CI 0.58-0.71) for predicting
      beta-lactam underdosing<4*MIC. Mean CLCr values >=170 mL/min were significantly
      associated with subexposure<4xMIC [OR = 10.1 (2.4-41.6); P = 0.001]. Patients
      with subexposure<4*MIC presented higher rates of therapeutic failure [OR = 6.3
      (1.2-33.2); P = 0.03]. Mean CLCr values >=170 mL/min remain a risk factor for
      subexposure to beta-lactams despite high doses of beta-lactams administered
      continuously. beta-Lactam subexposure was associated with higher rates of
      therapeutic failure in septic critically ill patients.

PMID- 29180281
TI  - Insertion sequence transpositions and point mutations in mgrB causing colistin
      resistance in a clinical strain of carbapenem-resistant Klebsiella pneumoniae
      from Vietnam.
AB  - Resistance among Klebsiella pneumoniae to the last-resort antibiotics carbapenems
      and colistin is increasing worldwide. In this study, whole-genome sequencing was
      used to determine the colistin resistance mechanisms in clinical isolates of
      carbapenem- and colistin-resistant K. pneumoniae from Vietnam. Alterations in the
      regulatory gene mgrB, via mutations and insertion sequence transpositions, were
      found in 30 of 31 isolates, emphasising the importance of this resistance
      mechanism in colistin-resistant K. pneumoniae.

PMID- 29180282
TI  - Antibiotic resistance genes in phage particles isolated from human faeces and
      induced from clinical bacterial isolates.
AB  - Phage particles have emerged as elements with the potential to mobilise
      antibiotic resistance genes (ARGs) in different environments, including the
      intestinal habitat. This study aimed to determine the occurrence of ARGs in phage
      particles present in faecal matter and induced from strains isolated from faeces.
      Nine ARGs (blaTEM, blaCTX-M-1 group, blaCTX-M-9 group, blaOXA-48, qnrA, qnrS,
      mecA, sul1 and armA) were quantified by qPCR in the phage DNA fractions of 150
      faecal samples obtained from healthy individuals who had not received antibiotic
      treatment or travelled abroad in the 3 months prior to sample collection. On the
      suspicion that the detected particles originated from bacterial flora, 82
      Escherichia coli and Klebsiella pneumoniae isolates possessing at least one
      identified ARG (blaTEM, blaCTX-M-1 group, blaCTX-M-9 group, armA, qnrA, qnrS and
      sul1) were isolated and their capacity to produce phage particles carrying these
      ARGs following induction was evaluated. Of 150 samples, 72.7% were positive for
      at least one ARG, with blaTEM and blaCTX-M-9 group being the most prevalent and
      abundant. Of the 82 isolates, 51 (62%) showed an increase in the number of copies
      of the respective ARG in the phage fraction following induction, with blaTEM,
      blaCTX-M-1 group, blaCTX-M-9 group and sul1 being the most abundant. Phages
      induced from the isolates were further purified and visualised using microscopy
      and their DNA showed ARG levels of up to 1010 gene copies/mL. This study
      highlights the abundance of phage particles harbouring ARGs and indicates that
      bacterial strains in the intestinal habitat could be source of these particles.

PMID- 29180283
TI  - Current Readings on Surgery for the Neonate With Hypoplastic Aortic Arch.
AB  - Aortic arch hypoplasia is commonly present in neonates born with ductal-dependent
      coarctation of the aorta. The ideal surgical repair of neonates with proximal
      arch hypoplasia continues to be debated. Controversy exists about the fate of the
      hypoplastic proximal aortic arch following surgical repair and whether that will
      eventually grow to normal size upon relief of the distal obstruction or will
      persist as a residual lesion that can affect the long-term outlook of those
      patients. There is new evidence that residual proximal arch hypoplasia and the
      shape of the reconstructed arch both have an important impact on vascular
      remodeling and on the subsequent development of hypertension. Those concerns
      about late outcomes despite what was originally deemed a successful repair in
      infancy, coupled with improved cardiopulmonary bypass and cerebral perfusion
      techniques that allow surgeons to address proximal arch hypoplasia with low
      morbidity, have rekindled the debate on how to address proximal arch hypoplasia,
      with the aim to offer a neonatal surgery that would last for a lifetime and
      provide both optimal early recovery and late freedom from hypertension and
      related complications.

PMID- 29180284
TI  - Reoperative Pulmonary Endarterectomy: Past Failures of Patient Selection Can
      Assist in Future Practice of Informed Consent.
AB  - The Pavia group reports their experience with reoperative pulmonary
      endarterectomy for patients with chronic thromboembolic pulmonary hypertension.
      They achieved impressive results in terms of hemodynamic parameters and
      functional status; however, a mortality rate of 40% represents inappropriate
      patient selection. Recommendations are made for identifying ideal operative
      candidates.

PMID- 29180285
TI  - Hsc70 regulates the IRES activity and serves as an antiviral target of
      enterovirus A71 infection.
AB  - Enterovirus A71 (EV-A71) is a small positive-stranded RNA virus that causes human
      hand, foot and mouth disease (HFMD) and fatal neurological disorders in some
      cases without effective treatment. Here we show that heat shock cognate protein
      70 (Hsc70), a molecular chaperone, displays pivotal role in viral infections.
      Knockdown of Hsc70 significantly suppresses viral replication evidenced by
      reducing not only the level of both viral replication intermediates (negative
      stranded RNA) and viral genomic RNA (positive stranded RNA), but also the level
      of viral protein expression; whereas ectopic expression of Hsc70 markedly
      promotes viral replication. Interestingly, depletion of Hsc70 decreases the IRES
      activity of EV-A71, and the ectopic expression of Hsc70 enhances the IRES
      activity accordingly. Further study shows that Hsc70 binds viral genomic RNA but
      does not directly interact with IRES. Moreover, we reveal that Hsc70 interacts
      with 2A protease and promotes eIF4G cleavage. More importantly, Hsc70 inhibitor
      Ver-155008 significantly protects cytopathic effects from EV-A71 infection and
      inhibits both IRES activity and viral reproduction in a dose-dependent manner.
      The cell viability assay shows that the IC50 and CC50 are 2.01 MUM and 47.67 MUM,
      respectively. These results demonstrate not only an important mechanism of Hsc70
      in facilitating EV-A71 replication, but also a target for antiviral drug
      development.

PMID- 29180286
TI  - The estimation of oxime efficiency is affected by the experimental design of
      phosphylated acetylcholinesterase reactivation.
AB  - Reactivation of acetylcholinesterase (AChE), an essential enzyme in
      neurotransmission, is a key point in the treatment of acute poisoning by nerve
      agents and pesticides, which structurally belong to organophosphorus compounds
      (OP). Due to the high diversity of substituents on the phosphorous atom, there is
      a variety of OP-AChE conjugates deriving from AChE inhibition, and therefore not
      only is there no universal reactivator efficient enough for the most toxic OPs,
      but for some nerve agents there is still a lack of any reactivator at all. The
      endeavor of many chemists to find more efficient reactivators resulted in
      thousands of newly-designed and synthesized oximes-potential reactivators of
      AChE. For an evaluation of the oximes reactivation efficiency, many research
      groups employ a simple spectrophotometric Ellman method. Since parameters that
      describe reactivator efficiency are often incomparable among laboratories, we
      tried to emphasize the critical steps in the determination of reactivation
      parameters as well as in the experimental design of a reactivation assay. We
      highlighted the important points in evaluation of reactivation kinetic parameters
      with an aim to achieve better agreement and comparability between the results
      obtained by different laboratories and overall, a more efficient evaluation of in
      vitro reactivation potency.

PMID- 29180287
TI  - Role of N-acetyltransferase 2 acetylation polymorphism in 4, 4'-methylene bis (2
      chloroaniline) biotransformation.
AB  - Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) catalyze the acetylation of
      arylamine carcinogens. Single nucleotide polymorphisms in the NAT2 coding exon
      present in NAT2 haplotypes encode allozymes with reduced N-acetyltransferase
      activity towards the N-acetylation of arylamine carcinogens and the O-acetylation
      of their N-hydroxylated metabolites. NAT2 acetylator phenotype modifies urinary
      bladder cancer risk following exposures to arylamine carcinogens such as 4
      aminobiphenyl. 4, 4'-methylene bis (2-chloroaniline) (MOCA) is a Group 1
      carcinogen for which a role of the NAT2 acetylation polymorphism on cancer risk
      is unknown. We investigated the role of NAT2 and the genetic acetylation
      polymorphism on both MOCA N-acetylation and N-hydroxy-MOCA O-acetylation. MOCA N
      acetylation exhibited a robust gene dose response in rabbit liver cytosol and in
      cryopreserved human hepatocytes derived from individuals of rapid, intermediate
      and slow acetylator NAT2 genotype. MOCA exhibited about 4-fold higher affinity
      for recombinant human NAT2 than NAT1. Recombinant human NAT2*4 (reference) and 15
      variant recombinant human NAT2 allozymes catalyzed both the N-acetylation of MOCA
      and the O-acetylation of N-hydroxy-MOCA. Human NAT2 5, NAT2 6, NAT2 7 and NAT2 14
      allozymes catalyzed MOCA N-acetylation and N-hydroxy-O-acetylation at rates much
      lower than the reference NAT2 4 allozyme. In conclusion, our results show that
      NAT2 acetylator genotype has an important role in MOCA metabolism and suggest
      that risk assessments related to MOCA exposures consider accounting for NAT2
      acetylator phenotype in the analysis.

PMID- 29180288
TI  - Study of potential transfer of aluminum to the brain via the olfactory pathway.
AB  - Many employees in the aluminum industry are exposed to a range of aluminum
      compounds by inhalation, and the presence of ultrafine particles in the workplace
      has become a concern to occupational health professionals. Some metal salts and
      metal oxides have been shown to enter the brain through the olfactory route,
      bypassing the blood-brain barrier, but few studies have examined whether aluminum
      compounds also use this pathway. In this context, we sought to determine whether
      aluminum was found in rat olfactory bulbs and whether its transfer depended on
      physicochemical characteristics such as solubility and granulometry. Aluminum
      salts (chloride and fluoride) and various nanometric aluminum oxides (13nm, 20nm
      and 40-50nm) were administered to rats by intranasal instillation through one
      nostril (10MUg Al/30MUL for 10days). Olfactory bulbs (ipsilateral and
      contralateral relative to instilled nostril) were harvested and the aluminum
      content was determined by graphite furnace atomic absorption spectrometry after
      tissue mineralization. Some transfer of aluminum salts to the central nervous
      system via the olfactory route was observed, with the more soluble aluminum
      chloride being transferred at higher levels than aluminum fluoride. No cerebral
      translocation of any of the aluminas studied was detected.

PMID- 29180289
TI  - Synthesis and antimalarial activity of 3'-trifluoromethylated 1,2,4-trioxolanes
      and 1,2,4,5-tetraoxane based on deoxycholic acid.
AB  - A series of new steroidal peroxides - 3'-trifluoromethylated 1,2,4-trioxolanes
      and 1,2,4,5-tetraoxanes based on deoxycholic acid were prepared via the reactions
      of the Griesbaum coozonolysis and peroxycondensation, respectively. 1,2,4
      Trioxolanes were synthesized by the interaction of methyl O-methyl-3-oximino
      12alpha-acetoxy-deoxycholate with CF3C(O)CH3 or CF3C(O)Ph and O3 as the mixtures
      of four possible stereoisomers at ratios of 1:2:2:1 and in yields of 50% and 38%,
      respectively. The major diastereomer of methyl 12alpha-acetoxy-5beta-cholan-24
      oate-3-spiro-5'-(3'-methyl-3'-trifluoromethyl-1',2',4'-trioxolane) was isolated
      via crystallization of a mixture of stereoisomers from hexane and its (3S,3'R)
      configuration was determined using X-ray crystallographic analysis.
      Peroxycondensation of methyl 3-bishydroperoxy-12alpha-acetoxy-deoxycholate with
      CF3C(O)CH3 or acetone led to 1,2,4,5-tetraoxanes in yields of 44% and 37%,
      respectively. Antimalarial activity of these new steroidal peroxides was
      evaluated in vitro against the chloroquine-sensitive (CQS) T96 and chloroquine
      resistant (CQR) K1 strains of Plasmodium falciparum. Deoxycholic acid 3'
      trifluoromethylated 1,2,4,5-tetraoxane demonstrated a good IC50 value against CQR
      strain (IC50 (K1) = 7.6 nM) of P. falciparum. Tetraoxane with the acetone subunit
      demonstrated the best results among all tested peroxides with an IC50 value of 3
      nM against the CQ-resistant K1 strain. In general, 1,2,4-trioxolanes of
      deoxycholic acid are less active than 1,2,4,5-tetraoxanes.

PMID- 29180291
TI  - Fish antimicrobial peptides (AMP's) as essential and promising molecular
      therapeutic agents: A review.
AB  - Antimicrobial peptides (AMPs) are generally considered as an essential component
      of innate immunity, thereby providing the first line of defense against wide
      range of pathogens. In addition, they can also kill the pathogens which are
      generally resistant to number of antibiotics, thereby providing the avenues for
      the development of future therapeutic agents. Fishes are constantly challenged by
      variety of pathogens which not only shows detrimental effect on their health but
      also increases risk of becoming resistant to conventional antibiotics. As fishes
      rely more on innate immunity, AMPs can serve as a potential defensive weapons in
      fishes for combating emerging devastating diseases. Generally, AMPs show
      multidimensional properties like rapid diffusion to the site of infection,
      recruitment of other immune cells to infected tissues and vigorous potential to
      rapidly neutralize broad range of pathogens (bacterial, fungal and viral). AMPs
      also exhibit diverse biological effect like endotoxin neutralization,
      immunomodulation and induction of angiogenesis in mammals. Due to these
      properties AMPs have become one of the most promising therapeutic agents to be
      studied. Till date, many AMPs have been isolated from the fishes but not fully
      characterized at molecular level. This review provides an overview of the
      structures, functions, and putative mechanisms of major families of fish AMPs.
      Further, we also highlighted how fish AMPs can be used as a novel therapeutic
      tool which is the theme of future research in drug development.

PMID- 29180292
TI  - NLRP3 inflammasome activation by mycobacterial ESAT-6 and dsRNA in intraocular
      tuberculosis.
AB  - The molecular basis of intraocular tuberculosis (TB) is not well understood. In
      this study, we investigated the role of two constituents of viable Mycobacterium
      tuberculosis - Early Secreted Antigenic Target-6 (ESAT-6), and mycobacterial RNA-
      in inflammasome activation in the retinal pigment epithelium (RPE), a key site of
      inflammation in intraocular TB. We found that ESAT-6 induced caspase-1 activation
      and inflammasome priming in mouse RPE cells, substantially more in wild-type than
      in Tlr2/3/4/7/9-/-, Myd88-/- or Nlrp3-/- RPE cells. Sub-retinal ESAT-6 injection
      resulted in greater RPE degeneration in wild-type than in Nlrp3-/- mice. In human
      ocular TB tissue sections, NLRP3 staining was noted in retina as well as RPE.
      Mycobacterial RNA, specifically its double stranded component, also induced
      caspase-1 activation, and the double stranded RNA was immunolocalized to human
      ocular TB sections. Our observations suggest that inflammasome activation in RPE
      by viable M. tuberculosis could potentially contribute to human intraocular TB.

PMID- 29180293
TI  - Development of indirect immunofluorescence assay for TCID50 measurement of grass
      carp reovirus genotype II without cytopathic effect onto cells.
AB  - Grass carp reovirus (GCRV) caused severe hemorrhagic disease with significant
      losses of fingerling and yearling grass carp, Cyenopharyngodon idellus, in
      southeast Asian. It was first isolated in 1983 in China, and clade analysis of
      the different GCRV isolates indicates there are at least three different
      genotypes I, II, and III. In recent years, GCRV genotype II has been determined
      as a dominant virus type which cause severe obvious clinical signs in fish but no
      cytopathic effect onto presently available cell culture. TCID50 is one of
      standard method to quantity infectious virus particles. In the present study, an
      indirect immunofluorescence assay (IFA) was developed using antibody against a
      protein encoded by segment 10 of GCRV genotype II. Moreover, the specific assay
      to differentitate GCRV of different genotypes and a sensitive assay for
      determination of GCRV genotype II were developed respectively. The results showed
      the IFA only can recognize genotype II virus at the lowest initial concentration
      of 550 genomic copies/ml. Furthermore, comparison of results obtained from qPCR
      and the TCID50 assay combined IFA was conducted. The results indicated that
      TCID50 of GCRV isolates JX0901 and HZ08 differs with 2 log steps reduction in the
      numbers of viruses compared with the number of genome copies detected by qPCR.
      The immunofluorescence assay developed is sensitive, specific, and the TCID50
      combined with IFA will be a standardizable technique for the quantitation and
      detection of infectious GCRV in cell culture without cytolysis.

PMID- 29180290
TI  - Estradiol and the control of feeding behavior.
AB  - This review lays out the evidence for the role of E2 in homeostatic and hedonic
      feeding across several species. While significant effort has been expended on
      homeostatic feeding research, more studies for hedonic feeding need to be
      conducted (i.e. are there increases in meal size and enhanced motivation to
      natural food rewards). By identifying the underlying neural circuitry involved,
      one can better delineate the mechanisms by which E2 influences feeding behavior.
      By utilizing more selective neural targeting techniques, such as optogenetics,
      significant progress can be made toward this goal. Together, behavioral and
      physiological techniques will help us to better understand neural deficits that
      can increase the risk for obesity in the absence of E2 (menopause) and aid in
      developing therapeutic strategies.

PMID- 29180296
TI  - Universal Lipid Screening in 9- to 11-Year-Olds Before and After 2011 Guidelines.
AB  - OBJECTIVE: To determine whether the 2011 guidelines for universal routine
      screening for dyslipidemia in children aged 9 to 11 years, published by the
      Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk
      Reduction in Children and Adolescents and National Heart, Lung, and Blood
      Institute, are being followed by pediatric primary-care providers. METHODS:
      Retrospective data were obtained for 63,951 well-child visits (WCV) in children
      aged 9 to 11 years from 2 health care systems and 1 insurance program from 2009
      to 2015. The proportion of WCV that had a lipid panel or total cholesterol test
      performed within 1 year of the visit was compared for 2009-2011 versus 2013-2015.
      Associations between demographic variables and lipid screening were evaluated
      with logistic regression. The frequency of tested children who had abnormal lipid
      results was evaluated. RESULTS: Only 3.5% of 9- to 11-year WCV had lipid tests
      performed in association with the visit before and after the guidelines. Of those
      tested, 43% had an abnormal lipid result. CONCLUSIONS: Utah clinicians rarely
      follow guidelines for universal lipid screening of children aged 9 to 11. This
      represents a missed opportunity to identify children at risk for early-onset
      cardiovascular disease.

PMID- 29180295
TI  - Antimicrobial and bactericidal impacts of Bacillus amyloliquefaciens CECT 5940 on
      fecal shedding of pathogenic bacteria in dairy calves and adult dogs.
AB  - Two experiments were carried out to evaluate the bactericidal impacts of Bacillus
      amyloliquefaciens CECT 5940 on the shedding of faecal pathogenic bacteria in
      dairy calves (Experiment 1) and in adults dogs (experiment 2). In the calves
      experiment, a completely randomized design was used to investigate the faecal
      bacteria profile of Holstein dairy calves fed with either pasteurized waste milk
      (PWM; n = 9) or a formulated non-medicated milk replacer (NMR; n = 9) for 60 d.
      The NMR containing sodium-butyrate and the active probiotic B. amyloliquefaciens
      CECT 5940. In the dogs experiment, addition of same probiotic (i.e., B.
      amyloliquefaciens CECT 5940) was carried out in two stages. The first stage
      started from day 7-37, and the second from day 44-71. The assessment of faecal
      score measured on day 22, 37, 42, 57, 71 and 77 to determine the texture of the
      stools. Calves received PWM consumed (P < 0.05) more starter feed between day 16
      and day 45. The calves fed NMR had more moisture faeces and less cough reflux
      than the PWM-calves. Feeding NMR to calves increased faecal Klebsiella oxytoca
      and Proteus vulgaris counts in comparison to PWM-calves. The administration of B.
      amyloliquefaciens CECT 5940 to the dog diet has no significant effect on the
      hardness of the stool. Meanwhile, the bacillus count increases while the
      coliforms count decreases upon B. amyloliquefaciens CECT 5940 administration.
      This reveals that B. amyloliquefaciens CECT 5940 survived the gastrointestinal
      passage and rapidly colonized the dog intestine, which could positively affect
      the metabolism and composition of the intestinal microflora. These results show
      that B. amyloliquefaciens are a promising probiotic with an antimicrobial and
      bactericidal activities against the intestinal pathogenic bacteria for dairy
      calves and adult dogs.

PMID- 29180294
TI  - Homeopathic treatment as an alternative prophylactic to minimize bacterial
      infection and prevent neonatal diarrhea in calves.
AB  - Bovine neonatal diarrhea is common due low immunity in newborn calves, poor
      management (or absence) of sanitary barriers, and other factors. Newborn calves
      with diarrhea in the first days of life suffer failure to thrive and may die if
      left untreated. The aim of this study was to evaluate whether prophylactic
      administration of a homeopathic product (Dia 100(r)) can control bovine neonatal
      diarrhea in calves born on a farm with substantial sanitary challenges. We
      counted total bacteria and protozoan parasites in fecal samples. We measured
      serum glucose, total protein, globulin, albumin, cholesterol and triglycerides on
      days 1, 7 and 14 of life. Twenty newborn calves were maintained in individual
      stalls, and were divided in two groups: ten untreated animals (control) and ten
      animals treated with Dia 100(r). Fecal consistency was evaluated daily. We
      diagnosed diarrhea in five animals in the treated group, and in all animals from
      the control group. Infections with Escherichia coli and Giardia duodenalis were
      identified as the responsible organisms. The E. coli count was low in the
      treatment group on day 7 of life compared with the control group. Antibiotics
      were given to eight animals in the control group, and to two animals in the
      treatment group. On day of life 7, serum levels of total protein and globulins
      were higher in the control group, but were lower on day 14. Serum levels of
      glucose and triglycerides were greater in treated animals on days 7 and 14,
      suggesting that the homeopathic product contributes to improvement of intestinal
      health and absorption and nutrients. We conclude that Dia 100(r) controls
      diarrhea with 50% of efficacy, and reduces antibiotic utilization.

PMID- 29180297
TI  - Development, Implementation, and Assessment of the Intensive Clinical Orientation
      for Residents (ICOR) Curriculum: A Pilot Intervention to Improve Intern Clinical
      Preparedness.

PMID- 29180298
TI  - Overexpressing cell systems are a competitive option to primary adipocytes when
      predicting in vivo potency of dual GPR81/GPR109A agonists.
AB  - Mathematical models predicting in vivo pharmacodynamic effects from in vitro data
      can accelerate drug discovery, and reduce costs and animal use. However, data
      integration and modeling is non-trivial when more than one drug-target receptor
      is involved in the biological response. We modeled the inhibition of non
      esterified fatty acid release by dual G-protein-coupled receptor 81/109A
      (GPR81/GPR109A) agonists in vivo in the rat, to estimate the in vivo EC50 values
      for 12 different compounds. We subsequently predicted those potency estimates
      using EC50 values obtained from concentration-response data in isolated primary
      adipocytes and cell systems overexpressing GPR81 or GPR109A in vitro. A simple
      linear regression model based on data from primary adipocytes predicted the in
      vivo EC50 better than simple linear regression models based on in vitro data from
      either of the cell systems. Three models combining the data from the
      overexpressing cell systems were also evaluated: two piecewise linear models
      defining logical OR- and AND-circuits, and a multivariate linear regression
      model. All three models performed better than the simple linear regression model
      based on data from primary adipocytes. The OR-model was favored since it is
      likely that activation of either GPR81 or GPR109A is sufficient to deactivate the
      cAMP pathway, and thereby inhibit non-esterified fatty acid release. The OR-model
      was also able to predict the in vivo selectivity between the two receptors.
      Finally, the OR-model was used to predict the in vivo potency of 1651 new
      compounds. This work suggests that data from the overexpressing cell systems are
      sufficient to predict in vivo potency of GPR81/GPR109A agonists, an approach
      contributing to faster and leaner drug discovery.

PMID- 29180299
TI  - Initial Imaging for Pediatric Renal Tumors: An Opportunity for Improvement.
AB  - PURPOSE: Current Children's Oncology Group studies on renal malignancy focus on
      minimizing treatment side effects with a goal of decreasing long-term
      complications. In this series we evaluate the patterns of initial imaging in
      children with renal tumors. MATERIALS AND METHODS: We retrospectively reviewed
      records of 122 patients treated for renal tumors at our institution between 2005
      and 2016. Ideal imaging was defined as cross-sectional imaging of the chest,
      abdomen and pelvis in a single setting without any additional ionizing radiation
      exposing scans. RESULTS: Median patient age was 33.5 months (range 1 to 195). A
      total of 101 patients (83%) were initially evaluated elsewhere and subsequently
      referred to oncology (67.2%) for further evaluation. Before treatment 58 patients
      (47.5%) underwent imaging that was obtained in an ideal manner. Compared to those
      undergoing ideal imaging, median additional radiation exposure was 2.31 mSv
      (range 0.9 to 11.5), 3.08 mSv (0.6 to 11.7) and 5.1 mSv (1.2 to 16) in patients
      younger than 5 years, 5 to 9 years old and 10 years or older, respectively.
      Factors associated with undergoing ideal imaging included undergoing abdominal
      ultrasound as an initial scan (OR 3.637, p = 0.001), while presentation to an
      emergency department resulted in a reduced likelihood of undergoing ideal imaging
      (OR 0.351, p = 0.012). Factors associated with a decreased likelihood of
      undergoing initial screening ultrasound included presenting with vague symptoms
      (OR 0.072, p = 0.045) and presenting to a tertiary care emergency department (OR
      0.228, p = 0.027). CONCLUSIONS: Current patterns of initial imaging for pediatric
      renal tumors are often associated with unnecessary and avoidable imaging studies,
      resulting in increased radiation exposure. Presenting to the emergency room as
      the initial point of contact with vague symptoms is associated with a decreased
      likelihood of undergoing appropriate or ideal pretherapy imaging, while initial
      evaluation with ultrasound is associated with a greater likelihood of undergoing
      ideal imaging, reducing overall radiation exposure. We advocate initial abdominal
      ultrasound in all pediatric patients suspected of having an abdominal mass. Our
      data highlight an opportunity for quality improvement across specialties caring
      for children with renal tumors.

PMID- 29180300
TI  - Variation in Spending around Surgical Episodes of Urinary Stone Disease: Findings
      from Michigan.
AB  - PURPOSE: To help rein in surgical spending there is growing interest in the
      application of payment bundles to common outpatient procedures like ureteroscopy
      and shock wave lithotripsy. However, before urologists can move to such a payment
      system they need to know where episode costs are concentrated. MATERIALS AND
      METHODS: Using claims data from Michigan Value Collaborative we identified
      patients who underwent ureteroscopy or shock wave lithotripsy at hospitals in
      Michigan from 2012 to 2015. We then totaled expenditures for all relevant
      services during the 30-day surgical episodes of these patients and categorized
      component payments (ie those for the index procedure, subsequent
      hospitalizations, professional services and postacute care). Finally we
      quantified the variation in total episode expenditures for ureteroscopy and shock
      wave lithotripsy across hospitals, examining drivers of this variation. RESULTS:
      A total of 9,449 ureteroscopy and 6,446 shock wave lithotripsy procedures were
      performed at 62 hospitals. Among these hospitals there was threefold variation in
      ureteroscopy and shock wave lithotripsy spending. The index procedure accounted
      for the largest payment difference between high vs low cost hospitals
      (ureteroscopy $7,936 vs $4,995 and shock wave lithotripsy $4,832 vs $3,207, each
      p <0.01), followed by payments for postacute care (ureteroscopy $2,207 vs $1,711
      and shock wave lithotripsy $2,138 vs $1,104, each p <0.01). Across hospitals the
      index procedure explained 68% and 44% of the variation in episode spending for
      ureteroscopy and shock wave lithotripsy, and postacute care payments explained
      15% and 28%, respectively. CONCLUSIONS: There exists substantial variation in
      ambulatory surgical spending across Michigan hospitals for urinary stone
      episodes. Most of this variation can be explained by payment differences for the
      index procedure and for postacute care services.

PMID- 29180301
TI  - When should ADULT CPR be delivered to children?

PMID- 29180302
TI  - Lost Memories of Winter: Breaking the FLC Silence.

PMID- 29180303
TI  - Effects of erythropoietin on astrocytes and brain endothelial cells in primary
      culture during anoxia depend on simultaneous signaling by other cytokines and on
      duration of anoxia.
AB  - Studies on animals revealed neuroprotective effects of exogenously applied
      erythropoietin (EPO) during cerebral ischemia/hypoxia. Yet, application of
      exogenous EPO in stroke patients often lead to haemorrhagic transformation. To
      clarify potential mechanism of this adverse effect we explored effects of EPO on
      viabilities of astrocytes and brain endothelial cells (BECs) in primary culture
      during anoxia of various durations, in the presence or absence of vascular
      endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), which are cytokines
      that are also released from the neurovascular unit during hypoxia. Anoxia (2-48
      h) exerted marginal effects on BECs' viability and significant reductions in
      viability of astrocytes. Astrocyte-conditioned medium did not exert effects and
      exerted detrimental effects on BECs during 2 h and 24 h anoxia, respectively.
      This was partially reversed by inhibition of Janus kinase (Jak)2/signal
      transducer and activator of transcription (STAT)5 activation. Addition of rat
      recombinant EPO (rrEPO) during 2 h-6h anoxia was protective for astrocytes, but
      had no effect on BECs. Addition of rrEPO significantly reduced viability of BECs
      and astrocytes after 48 h anoxia and after 24 h-48 h anoxia, respectively, which
      was attenuated by inhibition of Jak2/STAT5 activation. Simultaneous addition of
      rrEPO and VEGFA (1-165) caused marginal effects on BECs, but a highly significant
      protective effects on astrocytes during 24-48 h anoxia, which were attenuated by
      inhibition of Jak2/STAT5 activation. Simultaneous addition of EPO, VEGFA 1-165
      and Ang1 exerted protective effects on BECs during 24 h-48 h anoxia, which were
      attenuated by addition of soluble Tie2 receptor. These data revealed that EPO
      could exert protective, but also injurious effects on BECs and astrocytes during
      anoxia, which depended on the duration of anoxia and on simultaneous signaling by
      VEGF and Ang1. If these injurious effects occur in stroke patients, they could
      enhance vascular damage and haemorrhagic transformation.

PMID- 29180305
TI  - Pulmonary Vascular Resistance During Exercise Predicts Long-Term Outcomes in
      Heart Failure With Preserved Ejection Fraction.
AB  - BACKGROUND: In heart failure with preserved ejection fraction (HFpEF), the
      prognostic value of pulmonary vascular dysfunction (PV-dysfunction), identified
      by elevated pulmonary vascular resistance (PVR) at peak exercise, is not
      completely understood. We evaluated the long-term prognostic implications of PV
      dysfunction in HFpEF during exercise in consecutive patients undergoing invasive
      cardiopulmonary exercise testing for unexplained dyspnea. METHODS: Patients with
      HFpEF were classified into 2 main groups: resting HFpEF (n = 104, 62% female, age
      61 years) with a pulmonary arterial wedge pressure (PAWP) >15 mmHg at rest; and
      exercise HFpEF (eHFpEF; n = 81) with a PAWP <15 mmHg at rest, but >20 mmHg during
      exercise. The eHFpEF group was further subdivided into eHFpEF + PV-dysfunction
      (peak PVR >=80 dynes/s/cm-5; n = 55, 60% female, age 64) group and eHFpEF - PV
      dysfunction (peak PVR <80 dynes/s/cm-5; n = 26, 42% female, age 54 years) group.
      Outcomes were analyzed for the first 9 years of follow-up and included any cause
      mortality and heart failure (HF)-related hospitalizations. The mean follow-up
      time was 6.7 +/- 2.6 years (0.5-9.0). RESULTS: Mortality rate did not differ
      among the groups. However, survival free of HF-related hospitalization was lower
      for the eHFpEF + PV-dysfunction group compared with eHFpEF - PV-dysfunction (P =
      .01). These findings were similar between eHFpEF + PV-dysfunction and the resting
      HFpEF group (P = .774). By Cox analysis, peak PVR >=80 dynes/s/cm-5 was a
      predictor of HF-related hospitalization for eHFpEF (hazard ratio 5.73, 95%
      confidence interval 1.05-31.22, P = .01). In conclusion, the present study
      provides insight into the impact of PV-dysfunction on outcomes of patients with
      exercise-induced HFpEF. An elevated peak PVR is associated with a high risk of HF
      related hospitalization.

PMID- 29180306
TI  - Intraoperative Effect of Preoperative Gonadotropin-Releasing Hormone Analogue
      Administration in Women Undergoing Cold Loop Hysteroscopic Myomectomy: A
      Randomized Controlled Trial.
AB  - STUDY OBJECTIVE: To evaluate the intraoperative effects of gonadotropin-releasing
      hormone (GnRH) analogue pretreatment in patients undergoing cold loop
      hysteroscopic myomectomy. DESIGN: Randomized controlled trial (Canadian Task
      Force classification I). SETTING: Arbor Vitae Center for Endoscopic Gynecology,
      Rome, Italy. PATIENTS: A total of 99 patients were randomized and subsequently
      allocated to the GnRH analogue group or to the nonpharmacologic treatment control
      group. Fifteen patients were lost after allocation, and 42 patients per group
      underwent hysteroscopic myomectomy. INTERVENTIONS: Cold loop hysteroscopic
      myomectomy. MEASUREMENTS AND MAIN RESULTS: The control group accomplished the
      treatment in a 1-step procedure more frequently than the GnRH analogue group
      (92.85% and 73.8% of cases, respectively; p = .040). The completion of the
      treatment was more unlikely in case of G2 myomas (p = .006), whereas no
      differences were recorded for G1 and G0 myomas. The multivariate analysis showed
      a significant correlation between the multiple-step treatment and the use of GnRH
      analogue (odds ratio, 5.365; 95% confidence interval [CI], 1.018-28.284; p =
      .048), grading (odds ratio, 4.503; 95% CI, 1.049-19.329; p = .043), and size of
      myomas (odds ratio, 1.128; 95% CI, 1.026-1.239; p = .013). CONCLUSIONS:
      Preoperative GnRH analogue administration did not facilitate the completion of
      cold loop hysteroscopic myomectomy in a single surgical procedure in G2 myomas
      and was correlated with a longer duration of the surgery. No significant benefits
      were found for G0 and G1 myomas. (ClinicalTrials.gov: NCT01873378.).

PMID- 29180304
TI  - Functional analysis of corin protein domains required for PCSK6-mediated
      activation.
AB  - Atrial natriuretic peptide (ANP) is a cardiac hormone essential for normal blood
      pressure and cardiac function. Corin is a transmembrane serine protease that
      activates ANP. Recently, we identified proprotein convertase subtilisin/kexin-6
      (PCSK6), also called PACE4, as the long-sought corin activator. Both corin and
      PCSK6 are expressed in cardiomyocytes, but corin activation occurs only on the
      cell surface. It remains unknown if cell membrane association is needed for PCSK6
      to activate corin. Here we expressed corin deletion mutants in HEK293 cells to
      analyze the domain structures required for PCSK6-mediated activation. Our results
      show that soluble corin lacking the transmembrane domain was activated by PCSK6
      in the conditioned medium but not intracellularly. Recombinant PCSK6 also
      activated the soluble corin under cell-free conditions. Moreover, PCSK6-mediated
      corin activation was not enhanced by cell membrane fractions. These results
      indicate that cell membrane association is unnecessary for PCSK6 to activate
      corin. Experiments with monensin that blocks PCSK6 secretion and immunostaining
      indicated that the soluble corin and PCSK6 were secreted via different
      intracellular pathways, which may explain the lack of corin activation inside the
      cell. We also found that the protein domains in the corin pro-peptide region were
      dispensable for PCSK6-mediated activation and that addition of heparan sulfate
      and chondroitin sulfate or treatment with heparinase or chondroitinase did not
      alter corin activation by PCSK6 in HEK293 cells. Together, our results provide
      important insights into the molecular and cellular mechanisms underlying PCSK6
      mediated corin activation that is critical for cardiovascular homeostasis.

PMID- 29180307
TI  - Laparoscopic Sterilization Under Local Anesthesia with Conscious Sedation Versus
      General Anesthesia: Systematic Review of the Literature.
AB  - Female sterilization is the most popular and common contraceptive method
      worldwide. Because hysteroscopic sterilization techniques are used less often due
      to side effects, the number of laparoscopic sterilization is increasing. A
      systematic overview concerning the most optimal anesthetic technique for
      laparoscopic sterilization is lacking. We performed a systematic review to
      compare conscious sedation with general anesthesia for laparoscopic sterilization
      procedures with respect to clinical relevant outcome measures, such as operating
      times, perioperative parameters and complications, patient comfort, recovery, and
      patient satisfaction. We searched Cochrane Central Register of Controlled Trials,
      MEDLINE, and EMBASE for randomized controlled trials comparing general anesthesia
      with conscious sedation for laparoscopic sterilization. Two authors (AGH and
      HAAMvV) abstracted and entered data into RevMan. Methodologic quality of the
      included trials was critically appraised. For our main outcome measures mean
      differences (continuous variables) and risk ratios (dichotomous variables) with
      95% confidence intervals using random-effect models were calculated. Four
      randomized controlled trials were included comparing general anesthesia versus
      local anesthesia with conscious sedation for laparoscopic sterilization. The
      methodologic quality of the studies was moderate to good. Both techniques were
      comparable with regard to operating times, complications, and postoperative pain.
      However, local anesthesia with conscious sedation showed better results compared
      with general anesthesia with respect to recovery times, patient complaints of
      sore throat, and patient recovery and satisfaction. In conclusion, this
      systematic review about anesthetic techniques for laparoscopic sterilization
      showed that both general anesthesia and conscious sedation have no major
      anesthetic complications and may therefore be safe. Patients might benefit from
      conscious sedation in terms of recovery times, sore throat, and patient recovery
      and satisfaction, but only a few studies are included in the review and are
      relatively old. New research regarding this subject is needed to advise our
      patients most optimally in the future about the best anesthetic technique to be
      used when choosing for a laparoscopic sterilization procedure.

PMID- 29180308
TI  - Evidence-Based Medicine: Pandora's Box of Medical and Surgical Treatment of
      Endometriosis.

PMID- 29180309
TI  - Laparoscopic Excision vs Ablation for Endometriosis-Associated Pain: An Updated
      Systematic Review and Meta-Analysis.

PMID- 29180310
TI  - Author's Reply.

PMID- 29180311
TI  - Repeated Measurement of Fractional Exhaled Nitric Oxide Is Not Essential for
      Asthma Screening.
AB  - BACKGROUND AND OBJETIVE: Older guidelines recommend that fractional exhaled
      nitric oxide (FeNO) should be checked more than twice during the same session to
      confirm an asthma diagnosis. Recent studies show the excellent reproducibility of
      FeNO measurements. Objetive: We aimed to determine whether repeated FeNO
      measurements during the same session are necessary for asthma screening. MATERIAL
      AND METHODS: We retrospectively reviewed the electronic medical records of adult
      outpatients who visited the respiratory medicine department for diagnosis of
      asthma and assessed FeNO measurements obtained from June 2016 to July 2017.
      RESULTS: Of the 132 patients enrolled, 79 (59.8%) were diagnosed with asthma.
      Repeated FeNO measurements taken during the same session showed high
      reproducibility (intraclass correlation coefficient >0.9; P<.001) and a strong
      correlation (Pearson coefficient >0.9; P<.001), although reproducibility and
      correlation were slightly weaker in patients with low FeNO values. The value of
      repeated measurement was not significant; however, the second FeNO measurement
      was significantly higher than the first measurement in patients with the worst
      and best lung function. The predictive power of the first measurement of FeNO
      (sensitivity, 80.5%; specificity, 85.1%) was not inferior to the second
      (sensitivity, 76.6%; specificity 85.1%). The same was true of the geometric mean
      of the two. CONCLUSIONS: Repeated FeNO measurement during the same session is not
      essential for asthma screening in cases where the first acceptable FeNO
      measurement is performed using the proper method.

PMID- 29180312
TI  - Nevus depigmentosus with yellow hair colour due to an excess amount of
      benzothiazine-type pheomelanin.

PMID- 29180313
TI  - Segmental vitiligo treated by fire needle therapy: a case series.

PMID- 29180314
TI  - Leg ulcers as an atypical presentation of Mycobacterium leprae infection.

PMID- 29180315
TI  - A novel deletion mutation in the 2B domain of KRT5 in epidermolysis bullosa
      simplex with childhood-onset migratory circinate erythema.

PMID- 29180316
TI  - Dermoscopy and confocal microscopy for metachronous multiple melanomas:
      morphological, clinical, and molecular correlations.
AB  - Cutaneous melanoma is one of the most frequent malignancies of the skin in
      Caucasian populations. Patients who develop cutaneous melanoma are at increased
      risk of developing a second primary melanoma. The estimated incidence of multiple
      primary melanoma (MPM) ranges from 1.2% to 8.2% of cases, with a high
      preponderance of melanomas occurring metachronously. The aim of this study was to
      describe dermoscopic, microscopic, clinical, and molecular correlations between
      first and subsequent melanomas in patients with metachronous MPMs. Twenty-four
      paired melanomas from 12 MPM patients were evaluated for architectural
      characteristics based on dermoscopy and confocal microscopy, as well as for
      mutations in BRAF and NRAS genes by Sanger-based sequencing analysis. Specific
      scores used for classifying features of dermoscopy (global pattern; 7-point check
      list; ABCD Stolz score) and confocal microscopy (Segura and Pellacani) were
      compared with genetic and histological data. Consistency in dermoscopic patterns
      between the primary and subsequent cutaneous melanomas were observed in about two
      thirds of cases, whereas concordant features based on confocal microscopy were
      found in only about two fifths of cases. The majority of patients (7/12; 58%)
      presented consistent BRAF/NRAS mutation patterns between first and subsequent
      primary melanomas. A significant association between BRAF mutations and Pellacani
      score was evident. Similarities between the index melanoma and subsequent
      cutaneous melanomas were observed with regards to dermoscopic features and, to a
      much less extent, confocal microscopy findings. Our data further indicate that
      the Pellacani score may be used to predict BRAF mutations.

PMID- 29180317
TI  - A case series of paediatric and adolescent melanoma.

PMID- 29180318
TI  - A novel base pair deletion in the TRPS1 gene in a Japanese patient with
      trichorhinophalangeal syndrome.

PMID- 29180319
TI  - Wolf's isotopic response: Lichen planus patterns on non-segmental muco-cutaneous
      vitiligo.

PMID- 29180320
TI  - [Low expression of lncRNA-GAS5 promotes epithelial-mesenchymal transition of
      breast cancer cells in vitro].
AB  - OBJECTIVE: To investigate the role of long non-coding RNA growth arrest-specific
      transcript 5 (lncRNA-GAS5) in breast cancer progression and epithelial
      mesenchymal transition (EMT) of the cancer cells. METHODS: Real-time quantitative
      PCR (qRT-PCR) was used to detect the expression of lncRNA-GAS5 in 37 pairs of
      breast cancer and adjacent non-tumor tissues and in parental MCF-7 cells and
      paclitaxel-resistant MCF-7 (MCF-7/PR) cells, and the correlation of lncRNA-GAS5
      expression with the clinical stage and lymph node metastasis of breast cancer was
      investigated. The expressions of the genes related with cell cycle and EMT at
      both the mRNA and protein levels were detected using qRT-PCR, Western blotting
      and immunohistochemistry. The changes in the biological behaviors and morphology
      of breast cancer cells with either lncRNA-GAS5 knockdown or overexpression were
      observed. Nude mouse models were established bearing breast cancer xenografts
      derived from MCF-7/PR cells or MCF-7/PR cells over-expressing lncRNA-GAS5, and
      the inhibitory effect of paclitaxel on tumor growth was evaluated. RESULTS: The
      transcriptional levels of lncRNA-GAS5 were significantly lower in breast cancer
      tissues than in the adjacent non-tumor tissues (P<0.05), and decreased lncRNA
      GAS5 expression was significantly correlated with TNM stage and lymph node
      metastasis of breast cancer (P<0.05). lncRNA-GAS5 expression was also
      significantly lowered in paclitaxel-resistant breast cancer cells and showed a
      positive correlation with P21 expression and a negative correlation with CDK6.
      MCF-7 cells during EMT presented with a lowered expression of lncRNA-GAS5,
      whereas lncRNA-GAS5 over-expression strongly suppressed MCF-7/PR cell migration
      and invasion, and increased the susceptibility of the cells to paclitaxel. In the
      tumor-bearing nude mouse models, lncRNA-GAS5 overexpression in the tumor cells
      obviously enhanced the inhibitory effect of paclitaxel on tumor growth and lung
      metastasis by reversing the EMT marker proteins. CONCLUSION: A decreased
      expression of lncRNA-GAS5 promotes lung metastasis of breast cancer by inducing
      EMT, suggesting the potential of lncRNA-GAS5 as a therapeutic target in breast
      cancer.

PMID- 29180321
TI  - [A recombinant adenovirus vector carrying murine interleukin-21 gene controls
      chronic HBV infection in mice].
AB  - OBJECTIVE: To investigate the effect of an adenovirus vector containing murine
      interleukin-21 gene (Ad-GFP-mIL-21) in virus clearance and on the production of
      HBV-specific antibodies in mice with persistent HBV infection. METHODS: ELISA and
      Western blot analysis were used to detect the expression of mIL-21 in the
      supernatant and cytoplasm of cultured HepG2.2.15 cells after infection by Ad-GFP
      mIL-21. Mouse models of chronic HBV infection established by in vivo transduction
      with rAAV8-1.3HBV were divided into 3 groups for treatment 12 weeks later with
      injection of Ad-GFP-mIL-21, GFP recombinant adenovirus or PBS via the tail vein.
      Serum levels of HBsAg, HBsAb, HBcAb, and mIL-21 in the mice were detected using
      ELISA, and the expression of Ad-GFP-mIL-21 in the organs was observed by
      fluorescent microscopy at different time points after the injection. RESULTS: Ad
      GFP-mIL-21 was capable of infecting HepG2.2.15 cells in vitro, and the levels of
      mIL-21 in the supernatant were correlated with the titers of adenovirus
      administered and the infection time. In the mice with persistent HBV infection,
      green fluorescence expression was observed almost exclusively in the liver on day
      4 after injection of Ad-GFP-mIL21, and serum levels of IL-21 increased
      significantly compared with the level before treatment (P<0.05). Although HBsAb
      was undetectable in both Ad-GFP-mIL21-injected and control mice on day 13, a
      significantly higher serum level of HBcAb was detected in the mice with Ad-GFP
      mIL21 injection (P<0.05). CONCLUSION: Ad-GFP-mIL-21 can efficiently express mIL
      21 in mice with chronic HBV infection to downregulate serum levels of HBsAg and
      promote HBcAb production, suggesting its efficacy in controlling chronic HBV
      infection.

PMID- 29180322
TI  - [Peripheral blood T cell TNF-alpha and IFN-gamma production stimulated by low
      molecular peptide of Mycobacterium tuberculosis heat-resistant antigen for
      differential diagnosis between pulmonary tuberculosis and latent tuberculosis
      infection].
AB  - OBJECTIVE: To investigate the effects of low molecular peptide of Mycobacterium
      tuberculosis heat-resistant antigen (Mtb-HAg-10k) on the production of tumor
      necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in peripheral
      blood T cells and test the feasibility of differential diagnosis between
      pulmonary tuberculosis (PTB) and latent tuberculosis infection (LTBI) by
      assessing the number of Mtb-HAg-10k-stimulated IFN-gamma-producing T cells.
      METHODS: Peripheral blood mononuclear cells (PBMCs) were separated from the
      peripheral blood of 10 healthy adults, 6 individuals with LTBI and 13 patients
      with PTB. The PBMCs were cultured in the presence of Mtb-HAg-10k obtained by
      ultrafiltration centrifugation, with Mtb-HAg and phytohaemagglutinin (PHA) as the
      controls. The proportions of TNF-alpha- and IFN-gamma-producing cells in the T
      cell subsets were detected by flow cytometry (FCM), and the number of IFN-gamma
      producing cells from patients with PTB and LTBI was detected with ELISPOT.
      RESULTS: Flow cytometry showed that Mtb-HAg-10k exposure resulted in a
      significantly higher proportion of TNF-alpha-producing gammadeltaT cells than
      that of IFN-gamma-producing gammadeltaT cells in the PBMCs (P<0.01). Compared
      with the PBMCs exposed to PHA, the PBMCs exposed to Mtb-HAg-10k exhibited a
      significantly greater proportion of gammadeltaT cells that produced both TNF
      alpha and IFN-gamma (P<0.01) but a significantly lower proportion of alphabetaT
      cells producing both TNF-alpha and IFN-gamma (P<0.01). Mtb-HAg-10k exposure of
      the PBMCs caused a significant reduction in the number of IFN-gamma-producing
      cells as compared with Mtb-HAg and PHA treatments (P<0.01), and this reduction
      was more obvious in PBMCs from patients with PTB than in those from individuals
      with LTBI (P<0.01). CONCLUSION: Mtb-HAg-10k can markedly induce gammadeltaT cells
      in the PBMCs to produce TNF-alpha and IFN-gamma, and detection of the number of
      IFN-gamma-producing cells in the PBMCs following Mtb-HAg-10k stimulation helps in
      the differential diagnosis between pulmonary tuberculosis and latent tuberculosis
      infection.

PMID- 29180323
TI  - [Pathogen analysis in patients with diabetic foot osteomyelitis using 16S rRNA
      high-throughput sequencing].
AB  - OBJECTIVE: To analyze the characteristics of pathogenic microorganisms in the
      infected bone tissues in patients with diabetic foot osteomyelitis (DFO) using
      16S rRNA high-throughput sequencing to facilitate rapid and accurate detection of
      pathogens and effective infection control. METHODS: Between September, 2016 and
      April, 2017, 16 patients with DFO were admitted in our department and infected
      bone specimens were obtained during debridement. The pathogenic microorganisms in
      the specimens were identified using both 16S rRNA high-throughput sequencing and
      automatic blood culture analyzer, and the characteristics of the microflora were
      analyzed based on 16S rRNA sequencing data in comparison with the results of
      blood culture. RESULTS: The results of 16S rRNA sequencing showed that bone
      tissues of DFO contained diverse and uniformly distributed pathogenic organisms,
      among which 20 (87%) dominant genera were identified with Prevotella as the most
      abundant pathogen. Both 16S rRNA sequencing and routine culture results suggested
      the domination of gram-negative bacteria among the pathogens in DFO bone tissues.
      16S rRNA sequencing, compared with routine culture, yielded a higher positivity
      rate (100% vs 88.24%) and detected a greater average number of pathogens (12.56
      vs 1.50) and a higher proportion of gram-negative bacteria (67.16% vs 50.00%) in
      the samples. 16S rRNA sequencing detected nearly all the pathogens identified by
      routine culture except for Escherichia coli, Serratia marcescens and Enterobacter
      cloaca, and identified 13 genera that failed to be detected by routine culture,
      including the obligate or strict anaerobes Anaerococcus, Veillonella,
      Bacteroides, Fusobacterium, Porphyromonas, Finegoldia, Prevotella,
      Peptostreptococcus, Parvimonas, Peptoniphilus and Bulleidia. Routine culture did
      not detect any anaerobes in the samples but identified multidrug-resistant
      strains in as many as 58.33% of the pathogens. CONCLUSIONS: 16S rRNA high
      throughput sequencing is capable of demonstrating the diversity and abundance of
      microflora in DFO bone tissues, where diverse and uniformly distributed pathogens
      can be detected with a discrete distribution of the dominant genera, most of
      which are gram-negative. Compared with routine culture method, 16S rRNA
      sequencing allows more convenient and accurate identification of the pathogens
      (especially gram-negative bacteria and anaerobes), and can be useful in clinical
      decision on appropriate treatment of DFO.

PMID- 29180324
TI  - [Effects of simvastatin on aortic vascular endothelial cell apoptosis and Bcl-2
      protein expression in a rat model of atherosclerosis].
AB  - OBJECTIVE: To explore the effects of simvastatin on vascular endothelial cell
      apoptosis and Bcl-2 protein expression in the aorta in a rat model of
      atherosclerosis. METHODS: Thirty-six rats were randomized into control group
      (n=10), atherosclerosis model group (n=13) and simvastatin intervention group
      (n=13). In the latter two groups, rat models of atherosclerosis were established
      by intraperitoneal injection of vitamin D3 combined with high-fat feeding for 6
      weeks, and the control rats were fed with regular diet. In the intervention
      group, the rats were further fed with high-fat diet with daily simvastatin
      treatment for 4 weeks. After the treatments, the pathological changes and plaque
      in the thoracic aorta were observed, and the expression of Bcl-2 protein was
      detected with immunohistochemistry. TUNEL assay was used to determine the
      apoptosis index (AI) of the vascular endothelial cells. RESULTS: Compared with
      that in the control group, Bcl-2 protein expression in the aorta of
      atherosclerotic rats was significantly decreased (P<0.05); simvastatin treatment
      obviously increased the expression of Bcl-2 protein in atherosclerotic rats
      (P<0.05) to a level similar to that in the control group. The AI was the highest
      in the model group (P<0.05) and comparable between the control and simvastatin
      treatment group. CONCLUSION: The therapeutic effect of simvastatin against
      atherosclerosis is probably mediated by up-regulation of Bcl-2 protein, which
      inhibits vascular endothelial cell apoptosis in rats with aortic atherosclerosis.

PMID- 29180325
TI  - [Correlation between ectopic fat accumulation and insulin sensitivity in obese
      individuals with different glucose tolerance levels].
AB  - OBJECTIVE: To investigate the correlation between liver and skeletal muscle fat
      contents and insulin resistance in obese individuals with different levels of
      glucose tolerance. METHODS: RESULTS: Ten non-obese individuals with normal
      glucose tolerance (NGT), 9 obese individuals with NGT, and 7 obese individuals
      with impaired glucose tolerance (IGT) were enrolled in this study. All the
      participants were examined for insulin sensitivity by hyperinsulinemic-euglycemic
      clamp and for liver and skeletal muscle fat accumulation quantified by proton
      magnetic resonance spectroscopy (1H MRS). The data were collected from the
      subjects including somatometric measurements, fasting plasma glucose, 2-h plasma
      glucose (2hPG), fasting insulin, and blood biochemistry. Linear correlation
      analysis and multiple linear stepwise regression analysis were used to analyze
      the relationship between ectopic fat accumulation and insulin resistance.
      RESULTS: The glucose infusion rates (GIR, presented as the M value) differed
      significantly among IGT-obese (3.95?1.66 mg.kg-1.min-1), NGT-obese (6.14?1.90
      mg.kg-1.min-1) and NGT-non-obese (8.78?2.46 mg.kg-1.min-1) groups (P<0.05). The 3
      groups also showed significant differences in liver fat contents [(15.23?3.09)%,
      (6.25?0.38)%, and (1.89?0.90)%, respectively, P<0.05] and intramyocellular lipids
      in the tibialis anterior (2.69?0.95, 2.61?1.45, and 1.54?0.66 mmol/kg,
      respectively, P<0.05). Linear analysis revealed that liver fat content, but not
      skeletal muscle fat content, was significantly correlated with the M value.
      Multiple linear stepwise regression analysis using M value as the dependent
      variable (Y) revealed that liver fat content (X) was an independent factor
      inversely correlated with the M value (regression equation: Y=-30.562X+9.007,
      R2=0.717, P<0.01). CONCLUSIONS: Liver fat accumulation, but not skeletal muscle
      fat accumulation, is correlated with insulin resistance and impaired glucose
      metabolism.

PMID- 29180326
TI  - [Total knee arthroplasty with 3D printing technique versus conventional surgery:
      comparison of the outcomes].
AB  - OBJECTIVE: To compare the clinical outcomes of patients receiving total knee
      arthroplasty (TKA) using 3D printing technique and conventional surgical methods.
      METHODS: From October, 2015 to February, 2017, 17 patients (20 knees) underwent
      TKA with the assistance of individualized navigation template and 16 concurrent
      patients (18 knees) matched for age, gender and knee society score received
      conventional TKA. The operation time, blood loss, and osteotomy data of the
      femoral condyle and tibia plateau were recorded. The mean femorotibial angle
      (MFTA) and sagittal tibial component angle (STCA) after the operation and the KSS
      at the last follow-up were compared between the two groups. RESULTS: All the
      patients were followed up for 7-23 months, during which no infection or
      prosthesis loosening or motion was found. In patients receiving surgery with 3D
      printing technique, the osteotomy data of the femoral condyle and tibia plateau
      in the actual surgeries were consistent with those in surgical plans (P>0.05).
      The patients in the 3D group had a significantly shorter operation time and a
      higher KSS score than those in the conventional group (P<0.05). Significant
      differences were found between the two groups in postoperative MFTA and STCA
      (P<0.05). CONCLUSION: The application of 3D printing technique can simplify the
      surgical procedure and improve the surgical precision and efficacy of TKA.

PMID- 29180327
TI  - [A probability model for analyzing speckles in intravascular ultrasound images to
      facilitate image segmentation].
AB  - OBJECTIVE: Ultrasonic image speckles result from the interference of the
      reflected signals by the scatters in the detected tissue. The physical
      characteristics of the speckles are closely correlated with the structures of the
      biological tissues, and the probability distribution of these speckles differs
      across different tissues. Based on the probability characteristics of
      intravascular ultrasound (IVUS) speckles, a Gamma mixture model and Gaussian
      mixture model are proposed to describe the calcified plaque, soft plaque and
      normal vascular regions on IVUS images. Using KS test, KL divergence and
      correlation coefficient analysis, we found that the probability distributions of
      the speckles generated by calcified plaques and normal blood vessels were better
      described by the Gaussian mixture model, while the speckles caused by soft
      plaques were described better by the Gamma mixture model. Based on this finding,
      we propose a probability mixture model combining neighborhood information for
      plaque segmentation on IVUS images. Compared with the existing probabilistic
      mixture model, the segmentation accuracy was greatly improved with a reduced
      noise.

PMID- 29180328
TI  - [Small interfering RNA-mediated alpha-enolase knockdown suppresses glycolysis and
      proliferation of human glioma U251 cells in vitro].
AB  - OBJECTIVE: To investigate the role of alpha-enolase (ENO1) in regulating glucose
      metabolism and cell growth in human glioma cells. METHODS: Glucose uptake and
      lactate generation were assessed to evaluate the changes in glucose metabolism in
      human glioma U251 cells with small interfering RNA (siRNA)-mediated ENO1
      knockdown. MTT assay and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to
      examine the cell growth and cell cycle changes following siRNA transfection of
      the cells. RESULTS: Transfection of U251 cells with siRNA-ENO1 markedly reduced
      glucose uptake (P=0.023) and lactate generation (P=0.007) in the cells and
      resulted in significant suppression of cell proliferation (*P<0.05) since the
      second day following the transfection. Transfection with siRNA-ENO1 also
      obviously suppressed cell cycle G1/S transition in the cells (P=0.0425). The
      expressions of HK2 and LDHA, the marker genes for glucose metabolism, were
      significantly down-regulated in the cells with siRNA-mediated ENO1 knockdown.
      CONCLUSION: ENO1 as a potential oncogene promotes glioma cell growth by
      positively modulating glucose metabolism.

PMID- 29180329
TI  - [Effects of aldosterone on osteoblast proliferation, differentiation and
      osteogenic gene expressions in vitro].
AB  - OBJECTIVE: To study the effect of aldosterone on cell proliferation, alkaline
      phosphatase (AKP) activity and osteogenic gene expression in rat osteoblasts and
      explore the mechanisms. METHODS: Osteoblasts isolated from the skull of neonatal
      SD rats by enzyme digestion were cultured and treated with different
      concentrations of aldosterone. The cell proliferation and AKP activity were
      evaluated using CCK-8 assay kit and AKP assay kit, respectively. The effects of
      aldosterone on mRNA and protein expressions of the osteogenic genes and
      epithelial sodium channel (ENaC) gene were investigated using semi-quantitative
      PCR and Western blotting. RESULTS: Compared with the control cells, the cells
      treated with 0.01-1.0 umol/L aldosterone showed obviously enhanced proliferation
      while lower (1*10-3 umol/L) or higher (10 umol/L) concentrations of aldosterone
      did not significantly affect the cell proliferation. Aldosterone within the
      concentration range of 1*10-3 to 10 umol/L did not cause significant changes in
      AKP activity in the osteoblasts. Treatment with 0.01 to 1.0 umol/L aldosterone
      significantly upregulated the expressions of the osteogenic genes and alpha-ENaC
      gene at both the mRNA and protein levels. CONCLUSION: Aldosterone within the
      concentration range of 0.01-1.0 umol/L stimulates the proliferation and
      osteogenic gene expressions and enhances alpha-ENaC gene expression in rat
      osteoblasts in vitro, suggesting the possibility that ENaC participates in
      aldosterone-mediated regulation of osteoblast functions.

PMID- 29180330
TI  - [Role of lncRNA PTENP1 in tumorigenesis and progression of bladder cancer and the
      molecular mechanism].
AB  - OBJECTIVE: To explore the molecular mechanism underlying the biological function
      of lncRNA PTENP1 in bladder cancer. METHODS: Expressions of PTENP1, PTEN and miR
      17 were examined by quantitative reverse transcriptase PCR (qRT-PCR) in 12
      bladder cancer tissues. The expression of PTEN was examined by Western blotting
      in bladder cancer cell lines T24 and 5637 overexpressing PTENP1. Luciferase
      reporter assay was performed to confirm the targeting of miR-17 to PTENP1 and
      PTEN. T24 and 5637 cell lines with stable overexpression of PTENP1 and mir-17
      were used to investigate effect of PTNE and miR-17 on the function of PTENP1 in
      bladder cancer. RESULTS: The expression of miR-17 was up-regulated and PTENP1 and
      PTEN were down-regulated in bladder cancer tissues, where a positive correlation
      was found between PTENP1 and PTEN expressions and a negative correlation between
      PTENP1 and miR-17 (P<0.05). Overexpression of PTENP1 in bladder cancer cell lines
      T24 and 5637 obviously enhanced the expression of PTEN protein. miR-17 was found
      to target both PTENP1 and PTEN and promote the growth of bladder cancer. miR-17
      could partially restore the tumor-suppressing activity of PTENP1 in bladder
      cancer. CONCLUSION: By binding with miR-17, lncRNA PTENP1 functions as a PTEN
      competing endogenous RNA (ceRNA) to suppress the progression of bladder cancer.

PMID- 29180331
TI  - [Effects of luteinizing hormone supplementation on outcomes of in vitro
      fertilization and embryo transfer in patients undergoing GnRH-agonist long
      protocol].
AB  - OBJECTIVE: To compare the clinical outcomes of in vitro fertilization and embryo
      transfer (IVF-ET) among patients in different conditions receiving luteinizing
      hormone supplementation in GnRH-agonist long protocol. METHODS: Between June,
      2010 and December, 2015, 671 IVF-ET cycles with GnRH-agonist long protocol were
      performed at our center. These cycles were divided into group A with FSH only and
      group B with FSH and recombinant luteinizing hormone (r-LH) supplementation, and
      each group was divided into 4 subgroups according to age (<35 or >=35) and the LH
      level on the initial day (<1.0 U/L or >=1.0 U/L). The effects of LH
      supplementation on the clinical pregnancy rate and implantation rate were
      compared among different subgroups. RESULTS: No statistical significances were
      found between groups A and B in age, body mass index (BMI), basal FSH, basal LH,
      basal E2, Gn dosage, Gn day, LH on HCG day, E2 on HCG day, P on HCG day, number
      of oocytes, fertilization rate, available embryo rate or good quality embryo rate
      per oocyte, but the endometrium thickness on HCG day differed significantly
      between the two groups. In women below 35 years of age with a LH level on HCG day
      over 1.0 U/L, r-LH supplementation resulted in a clinical pregnancy rate of 60%,
      significantly lower than the rate of 79.55% in women without r-LH supplementation
      (P<0.05). In women over 35 years with a LH level below 1.0 U/L, r-LH
      supplementation resulted in an implantation rate of 44.74%, as compared with
      24.74% in women without r-LH supplementation (P<0.05). CONCLUSION: In the long
      protocol, LH supplementation does not improve the oocyte number, fertilization
      rate, or good quality embryo per oocyte, and does not bring benefits to women
      below 35 years with a low LH level (<1.0 U/L) or those over 35 years with normal
      LH level (>=1.0 U/L) after GnRH-agonist administration. But for women over 35
      years with low LH levels, r-LH supplementation may improve the clinical pregnancy
      rate and implantation rate of IVF-ET cycles.

PMID- 29180332
TI  - [Effect of dexmedetomidine postconditioning on myocardial ischemia-reperfusion
      injury and inflammatory response in diabetic rats].
AB  - OBJECTIVE: To investigate the effect of dexmedetomidine postconditioning in
      alleviating myocardial ischemia-reperfusion (IR) injury and inflammation in
      diabetic mellitus rats. METHODS: Thirty normal male Sprauge Dawley (SD) rats were
      randomly allocated into 3 groups (n=10), namely the sham-operated group, IR
      group, and dexmedetomidine postconditioning (DP) group. Similarly, another thirty
      diabetic SD rats were also randomly allocated into diabetic sham (DM-S) group,
      diabetic IR (DM-IR) group and diabetic dexmedetomidine postconditioning (DM-DP)
      group. The mean arterial pressure (MAP), heart rate (HR) and the rate pressure
      product (RPP) were recorded at baseline, after 30 min of ischemia, and at 30 and
      120 min during reperfusion. Myocardial infarct size was analyzed by TTC double
      staining method, and plasma levels of CTnI, TNF-a, IL-6, IL-10 and IL-1beta were
      measured at 120 min of reperfusion. RESULTS: Compared with those in the sham
      operated group, normal and diabetic rats in IR and DP groups showed significantly
      lowered MAP, HR, and RPP and increased levels of plasma CTnI, TNF-a, IL-6, IL-10
      and IL-1beta levels after 30 min of ischemia and at 30 min and 120 min of
      reperfusion (P<0.05). Compared with those in the IR group, the normal rats in DP
      group showed decreased MAP, HR, and RPP at 30 min of ischemia and at 30 min of
      reperfusion, which increased at 120 min of reperfusion (P<0.05); the infarct size
      and plasma CTnI, TNF-a, IL-6 and IL-1beta levels were decreased while IL-10 was
      increased in DP group (P<0.05). Compared with those in DP group, the rats in DM
      DP group showed similar MAP, HR and RPP (P>0.05) but significantly increased
      infarct size and plasma CTnI, TNF-a, IL-6 and IL-1beta levels (P<0.05).
      CONCLUSION: Dexmedetomidine postconditioning may produce a cardioprotective
      effect against myocardial IR injury in normal rats by alleviating inflammation,
      but can not reduce the release of inflammatory mediators in diabetic rats to
      improve myocardial infarction.

PMID- 29180333
TI  - [Expressions of survivin, PI3K and AKT in keratinocytes in skin lesions and their
      pathogenic role in psoriasis vulgaris].
AB  - OBJECTIVE: To explore the role of survivin and PI3K/AKT pathway in the
      pathogenesis of psoriasis vulgaris (PV). METHODS: Plaque-like lesions collected
      from 22 patients with PV in progressive stage and 18 normal control skin
      specimens were examined using immunohistochemical staining, Western blotting and
      real-time quantitative PCR for expressions of survivin, PI3K and AKT in the
      keratinocytes, and their correlation was analyzed. A small interfering RNA
      (siRNA) was used to knock down AKT in cultured HaCaT cells, and Western blotting
      was used to detect the changes in the expression of survivin. RESULTS Compared
      with normal skin, PV lesions showed obviously up-regulated expressions of
      survivin, PI3K and AKT in the keratinocytes. Survivin expression was positively
      correlated with PI3K (r=0.4510, P=0.0351) and AKT (r=0.4423, P=0.0393) in the
      keratinocytes in PV lesions. In cultured HaCaT cells, siRNA-mediated knockdown of
      AKT caused down-regulation of survivin expression. CONCLUSION: Survivin and
      PI3K/AKT signaling pathway may participate in the occurrence and progression of
      PV.

PMID- 29180334
TI  - [Quantitative and comparative proteomics analysis in clear cell renal cell
      carcinoma and adjacent noncancerous tissues by 2-D DIGE].
AB  - OBJECTIVE: To identify specific protein markers for renal cell carcinoma
      detection and diagnosis, as well as develop new potential therapeutic targets of
      the disease. METHODS: We used two-dimensional difference in-gel electrophoresis
      (2-D DIGE) technique conjunction with mass spectrometry (MS) for the
      identification of significant differentially expressed proteins between 15cases
      of paired clear cell renal cell carcinoma (ccRCC) and adjacent normal renal
      tissues. The protein spots were considered as differentially expressed if a 1.5
      fold altered expression level was observed (Student's t test, P value<0.05).
      RESULTS: Of the 27 differentially expressed protein spots, 26 proteins were
      successfully identified. 11 proteins up-regulated in renal cell carcinoma,15
      proteins down-regulated. Among them Short/branched chain specific acyl-CoA
      dehydrogenase, mitochondrial (ACDSB), Aldose 1-epimerase (GALM), Peroxiredoxin-4
      (PRDX4), Macrophage-capping protein (CAPG), Beta-defensin 107 (D107A),
      Microfibril-associated glycoprotein 4 (MFAP4) were first time screening as new
      differential expressed proteins by protomic study in renal cell carcinoma.
      CONCLUSIONS: 2-D DIGE is a useful technique for screening and analysis
      differential expressed proteins in renal cell carcinoma. These new differently
      expressed proteins may be useful for development new molecular markers for the
      tumor.

PMID- 29180335
TI  - [Pathogenic role of leukotriene B4 in pulmonary microvascular endothelial cell
      hyper- permeability induced by one lung ventilation in rabbits].
AB  - OBJECTIVE: To elucidate the pathogenic role of leukotriene B4 (LTB4) in increased
      pulmonary microvascular endothelial cell permeability induced by one lung
      ventilation (OLV) in rabbits. METHODS: Forty-eight healthy Japanese white rabbits
      were randomly divided into control group (group C), saline pretreatment group
      (group S), bestatin (a leukotriene A4 hydrolase (LTA4H) inhibitor) plus saline
      pretreatment group (group B), OLV group (group O), saline pretreatment plus OLV
      group (group SO) and bestatin plus saline pretreatment with OLV group (group BO).
      ELISA was used to detect LTB4 content in the lung tissues, and LTA4H and
      phospholipase Cepsilonl (PLCEl) expressions were examined by Western blotting and
      quantitative PCR. The wet/dry weight (W/D) ratio of the lung, lung permeability
      index and the expressions of myosin light chain kinase (MLCK) protein and mRNA in
      the lung tissues were determined to evaluate the permeability of the pulmonary
      microvascular endothelial cells (PMVECs). The severities of lung injury were
      evaluated by lung histomorphological scores. RESULTS: No significant differences
      were found among groups C, S and B except that LTA4H expressions was
      significantly lower in group B than in groups C and S (P<0.05). OLV significantly
      increased the expressions of LTA4H (P<0.05) and resulted in LTB4 overproduction
      in the lungs (P<0.05) accompanied by significantly enhanced PLCE1 expression and
      PMVEC permeability (P<0.05). Pretreatment with bestatin, significantly reduced
      the expression of LTA4H and LTB4 production (P<0.05) and down-regulated the
      expression of PLCE1 in the lungs of the rabbits receiving OLV (P<0.05).
      CONCLUSION: Bestatin plays a protective role in OLV-induced rabbit lung injury by
      downregulating LTA4H to reduce the production of LTB4 in the lungs. LTB4 can
      increase PMVEC permeability by up-regulating PLCE1 expression in rabbits with OLV
      induced lung injury.

PMID- 29180336
TI  - [Protective effects of rutin against obesity-induced reproductive impairment in
      male mice].
AB  - OBJECTIVE: To study the effect of rutin on body weight and obesity-induced
      reproductive impairment in male mice. METHODS: Twenty-four male mice were
      randomized equally into normal control group, high-fat diet group (HFD group),
      and HFD + rutin intervention group (HRU group). After 28 days of treatments, the
      testes and epididymis of the mice were collected for detection of total
      cholesterol (TC) and triglycerides (TG) levels and for pathological examinations
      with HE staining. The expressions of related genes was detected with real-time
      PCR, and Western blotting was used to detect the expression of Ucp1 protein in
      the samples. RESULTS: After 28 days of treatments, the mean body weight was lower
      in mice with rutin intervention than in those in HFD group. The mice in HFD group
      showed significantly higher TG levels in the testis and epididymis and higher TC
      levels in the epididymis than those in the control and HRU groups. In HFD group,
      the testis and the epididymis displayed loosened structures with abnormalcell
      structure, and the number ofmature spermatozoa in the lumen was decreased and the
      mobility of the sperms was reduced; all these changes were significantly
      alleviated in HRU group. The expression levels of Ucp1 mRNA and protein increased
      (P<0.05) and the expressions of Mcp1 and TNF-alpha decreased significantly in the
      mice after rutin treatment (P<0.05). CONCLUSION: Rutin can effectively inhibit
      rapid increase of body weight and protect against obesity-induced reproductive
      impairment in obese mice.

PMID- 29180337
TI  - [Effect of basic fibroblast growth factor antibody combined with irinotecan on
      proliferation and apoptosis of small cell lung cancer H223 cells in vitro].
AB  - OBJECTIVE: To study the synergistic inhibitory effects of basic fibroblast growth
      factor (bFGF) monoclonal antibody (bFGF mAb) and irinotecan on the proliferation
      of small cell lung cancer H223 cells. METHODS: CCK-8 assay and flow cytometry
      were used to assess the effects of bFGF mAb combined with irinotecan on the
      proliferation and apoptosis of H223 cells, respectively. Western blotting was
      performed to analyze the effect of bFGF-mAb combined with irinotecan on AKT and
      ERK1/2 phosphorylation in the cells. RESULTS: Both bFGF mAb and irinotecan alone
      inhibited H223 cell proliferation in a dose-dependent manner (P<0.05). The
      inhibitory rate was significantly higher in H223 cells treated with bFGF mAb +
      irinotecan (54.30%) than in cell treated with bFGF mAb (18.73%) or irinotecan
      (21.96%) alone (P<0.05). Both bFGF mAb and irinotecan induced H223 cell apoptosis
      in a dose-dependent manner (P<0.05), and the combined treatment resulted in a
      significantly higher early apoptosis rates (6.5%) than treatment with bFGF mAb
      (2.7%) or irinotecan (4.3%) alone (P<0.05). bFGF mAb and irinotecan, either alone
      or in combination, significantly inhibited the levels of p-AKT protein and p
      ERK1/2 protein without obviously affecting AKT and ERK1/2 protein levels.
      CONCLUSION: bFGF mAb and irinotecan produce synergistic inhibitory effects on
      small cell lung cancer H223 cells by suppressing proliferation and promoting
      apoptosis of the cells, and can effectively block the MAPK/ERK and PI3K/AKT
      signaling pathways associated with bFGF.

PMID- 29180338
TI  - [Association of waist-to-hip ratio with insulin resistance in non-diabetic normal
      weight individuals: a cross-sectional study].
AB  - OBJECTIVE: To explore the relationship between waist-to-hip ratio (WHR) and
      insulin resistance(IR) in non-diabetic normal-weight individuals and investigate
      how this association differs between male and femalesubjects. METHODS: From June
      to October, 2012, we performed a cross-sectional survey among 2142 community
      based non-diabetic Chinese participants, who were divided into 4 groups according
      to the gender-specific quartiles of WHR. Homeostatic model assessment of insulin
      resistance (HOMA-IR), calculated as the product of fasting plasma glucose
      (mmol/L) and fasting insulin (mU/L) divided by 22.5, was used as the indicator of
      insulin resistance. Logistic regression models were used to explore the
      association of WHR with IR in these subjects. RESULTS: In the unadjusted model,
      WHR was significantly associated with IR in women (OR=6.60, 95%CI: 2.86-15.26,
      P<0.001); the association was still significant (OR=3.28, 95%CI: 1.34-8.04,
      P=0.009) after adjustment for the potential confounders including the history of
      hypertension, coronary heartdisease, current smoker, physical inactivity, and
      body mass index. CONCLUSION: WHR is independently associated with IR in non
      diabetic Chinese women with normal body weight.

PMID- 29180339
TI  - [Deguelin inhibits proliferation and regulates the expression of MCM3-CDC45 in
      MCF-7 and H1299 cells in vitro].
AB  - OBJECTIVE: To observe the effects of deguelin on the proliferation of breast
      cancer MCF-7 cells and lung cancer H1299 cells in vitro and the expression of
      minichromosome maintenance protein 3 (MCM3) and CDC45 in the cells. METHODS: MTT
      assay was used to evaluate the proliferation of MCF-7 and H1299 cells exposed to
      different concentrations of deguelin for 48, 72 or 96 h. The growth of the cells
      was observed microscopically and the changes of MCM3 and CDC45 expressions in MCF
      7 and H1299 cells following deguelin treatment were detected with fluorescence
      quantitative PCR. RESULTS: The proliferation of MCF-7 cells was significantly
      inhibited by exposure to 0.25, 0.5, 1, 5, 10, 30, and 50 umol/L deguelin for 48,
      72, and 96 h in a concentration- and time-dependent manner. In MCF-7 cells, the
      IC50 of deguelin at 48, 72, and 96 h was 9, 3, and 2 umol/L, respectively.
      Deguelin treatments of H1299 cells at 0.5, 1, 5, 10, 30, 50, and 100 umol/L also
      resulted in a concentration- and time-dependent inhibition of the cell growth
      with an IC50 at 96 h of 2 umol/L. Optical microscopy of the cells revealed a
      decreased number of viable cells with obvious cell shrinkage following deguelin
      treatments. The expression of MCM3 and CDC45 were significantly reduced in the
      cells after deguelin treatments. CONCLUSION: Deguelin can inhibit the
      proliferation of MCF-7 and H1299 cells in vitro and down-regulate the expression
      of MCM3 and CDC45 in the cells.

PMID- 29180340
TI  - [Association between hepatocyte growth factor in tears and corneal haze in
      rabbits early after epipolis laser in situ keratomileusis].
AB  - OBJECTIVE: To study the dynamic changes of levels of hepatocyte growth factor
      (HGF) in tears and their association with corneal haze in rabbits early after
      epipolis laser in situ keratomileusis (Epi-LASIK). METHODS: Twenty-four New
      Zealand rabbits received Epi-LASIK with an ablation depth of 100 um in one eye
      and of 150 um in the other eye. Before and at 3, 7, 14, and 30 days after the
      surgery, the level of HGF in tears collected from the rabbits was measured using
      enzyme-linked immunosorbent assay (ELISA), and corneal haze was graded after
      surgery. RESULTS: In all the rabbits, corneal epithelium healing occurred in 3 to
      5 days after Epi-LASIK. Corneal haze appeared 3 days postoperatively in the
      rabbits accompanied by increased levels of HGF in tears. At 3, 7, 14, and 30 days
      after the surgery, the rabbits with an ablation depth of 150 um showed more
      obvious corneal haze (P<0.05) and significantly higher levels of HGF in tears
      than those with an ablation depth of 100 um (P<0.05). CONCLUSION: In rabbits
      receiving Epi-LASIK, HGF levels in tears and the grade of corneal haze show a
      positive correlation early after the surgery and are both related with the depth
      of ablation.

PMID- 29180341
TI  - [Surgical management of pregnancy-associated acute Stanford type A aortic
      dissection: analysis of 5 cases].
AB  - OBJECTIVE: To explore the diagnosis and treatment of pregnancy-associated acute
      Stanford type A aortic dissection to improve the maternal and fetal outcomes.
      METHODS: We analyzed the perioperative data of 5 pregnant women with acute
      Stanford type A aortic dissection treated between June, 2009 and February, 2017.
      RESULTS: The median age of the women was 30 years (range, 22-34 years) with
      gestational weeks of 23-38 weeks upon diagnosis. All the 5 patients received
      surgical interventions. Three patients underwent caesarean delivery and
      hysterectomy, and the fetuses survived after the surgery; 2 patients chose to
      continue pregnancy following the surgery, among whom one died due to
      postoperative complications and the other underwent termination of pregnancy.
      During follow-up, the surviving patients showed no endoleak in the descending
      aorta stent and the distal dissection remained stable. CONCLUSION: The maternal
      and fetal outcomes of pregnancy-associated acute Stanford type A aortic
      dissection can be improved by multidisciplinary cooperation and optimization of
      the surgical approaches according to the time of pregnancy, fetal development and
      conditions of the aortic lesions.

PMID- 29180342
TI  - [Progress and analysis methods of clinical application of extracellular
      vesicles].
AB  - OBJECTIVE: Extracellular vesicles (EVs) are small vesicles released by cells,
      which contain proteins and miRNA. It is a new research field in recent years. EVs
      change accordingly in a variety of diseases. These vesicles can sensitively
      reflect the pathological changes of the body. Compared with tissue biopsy, EVs
      detection have the advantages of non-invasive, simple sampling and real-time
      monitoring. EVs are becoming new diagnostic marker. This article reviews the
      current status and progress of EVs in clinical application.

PMID- 29180343
TI  - Mullerian Cyst in Posterior Mediastinum in a Young Woman.

PMID- 29180344
TI  - Behavioral Interventions to Prevent or Delay Dementia: Protocol for a Randomized
      Comparative Effectiveness Study.
AB  - BACKGROUND: Currently, people at risk for dementia and their caregivers are
      confronted with confusing choices about what behavioral interventions are most
      effective. OBJECTIVE: The objective of this study is to determine which
      empirically supported behavioral interventions most impact the outcomes highly
      valued by patients with mild cognitive impairment and their partners. METHODS:
      This protocol describes a comparative effectiveness trial targeting 300
      participants with mild cognitive impairment and their study partners. The trial
      is being conducted at the Mayo Clinic campuses in Arizona, Florida, Minnesota,
      and the University of Washington in Seattle. The study examines the contribution
      of five behavioral interventions (yoga, memory compensation training,
      computerized cognitive training, support groups, and wellness education) on
      primary outcomes of participant and partner quality of life and self-efficacy. In
      this unique 10-day multicomponent intervention, groups of couples were randomized
      to have one of the five interventions withheld while receiving the other four.
      Although the longitudinal follow-up is still under way, enrollment results are
      available and reported. RESULTS: In total, 272 couples have been enrolled in the
      trial and follow-up visits continue. Outcomes will be assessed at the end-of
      intervention and 6-, 12-, and 18-month follow-ups. We anticipate reporting on our
      primary and secondary outcomes across time points in the next 2 years.
      CONCLUSIONS: This paper describes the protocol for a randomized comparative
      effectiveness study of behavioral interventions to prevent or delay dementia. We
      describe of the rationale, design, power analysis, and analysis plan. Also
      because enrollment is complete and we are in follow-up phases of the study, we
      have included enrollment data from the trial. TRIAL REGISTRATION: 
      ClinicalTrials.gov NCT02265757; http://clinicaltrials.gov/ctsshow/ NCT02265757
      (Archived by WebCite at http://www.webcitation.org/6ueRfwSYv).

PMID- 29180345
TI  - In-Person Versus eHealth Mindfulness-Based Intervention for Adolescents With
      Chronic Illness: Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: Eight-week mindfulness-based interventions (MBIs) have a beneficial
      impact on mental health and well-being in adolescents with chronic health
      conditions. Usually delivered in person in a group setting, these programs are
      difficult to access for teens with disabilities or who do not have in-person MBIs
      available in their communities. OBJECTIVE: This paper outlines the rationale,
      development, and design of a randomized controlled trial comparing the effects of
      an MBI delivered in person or via eHealth in adolescents with a chronic illness.
      Quantitative outcomes will include mindfulness skills acquisition (primary
      outcome), effects of the MBI on self-reported mood, anxiety, self-esteem, illness
      perception, and physiological stress (via salivary cortisol), and qualitative
      outcomes will include individual practice, participant appreciation, and
      adaptation of the MBI for eHealth. METHODS: This is a randomized noninferiority
      mixed methods study comparing 2 MBI arms: in-person and eHealth. Participants are
      eligible to participate if they are aged 13 to 18 years, have a diagnosis of
      chronic medical condition, live close enough to the recruitment hospital to
      participate in the in-person arm of the study, and are currently followed by a
      health care provider. Each participant will receive an adapted 8-week MBI
      delivered either in person at a tertiary pediatric hospital or via a secure audio
      visual platform allowing group interactions in real time. Groups will be
      facilitated by 2 experienced mindfulness providers. Quantitative and qualitative
      data will be collected through standardized research questionnaires administered
      via a secure, youth-friendly online platform and through semistructured
      interviews, participant log books, facilitator log books, and salivary cortisol
      analysis. Qualitative data will be analyzed using a grounded theory model.
      RESULTS: Data collection is currently underway. Data analysis, manuscript
      writing, and additional publications are expected to be completed in the winter
      and spring of 2018. CONCLUSIONS: Based on previous results from in-person trials
      conducted in adolescents and eHealth trials conducted in adults, we anticipate
      that both modes of delivery will significantly improve mindfulness skills
      acquisition, mood, anxiety, self-esteem, illness perception, and stress and that
      the magnitude of the effects will be correlated to the level of home practice. We
      predict that participants in both arms will show similar levels of home practice
      and that both modes of delivery will have high levels of feasibility and
      acceptability. If successful, this study could provide evidence for the use of
      eHealth in the delivery of 8-week MBIs in clinical adolescent populations,
      potentially increasing availability to MBIs for a large group of youth with
      mobility issues or living away from large urban centers. TRIAL REGISTRATION:
      ClinicalTrials.org NCT03067207; https://clinicaltrials.gov/ct2/show/NCT03067207
      (archived by WebCite at http://www.webcitation.org/6v4ZK8RBH).

PMID- 29180346
TI  - Relationship Between the Menstrual Cycle and Timing of Ovulation Revealed by New
      Protocols: Analysis of Data from a Self-Tracking Health App.
AB  - BACKGROUND: There are many mobile phone apps aimed at helping women map their
      ovulation and menstrual cycles and facilitating successful conception (or
      avoiding pregnancy). These apps usually ask users to input various biological
      features and have accumulated the menstrual cycle data of a vast number of women.
      OBJECTIVE: The purpose of our study was to clarify how the data obtained from a
      self-tracking health app for female mobile phone users can be used to improve the
      accuracy of prediction of the date of next ovulation. METHODS: Using the data of
      7043 women who had reliable menstrual and ovulation records out of 8,000,000
      users of a mobile phone app of a health care service, we analyzed the
      relationship between the menstrual cycle length, follicular phase length, and
      luteal phase length. Then we fitted a linear function to the relationship between
      the length of the menstrual cycle and timing of ovulation and compared it with
      the existing calendar-based methods. RESULTS: The correlation between the length
      of the menstrual cycle and the length of the follicular phase was stronger than
      the correlation between the length of the menstrual cycle and the length of the
      luteal phase, and there was a positive correlation between the lengths of past
      and future menstrual cycles. A strong positive correlation was also found between
      the mean length of past cycles and the length of the follicular phase. The
      correlation between the mean cycle length and the luteal phase length was also
      statistically significant. In most of the subjects, our method (ie, the calendar
      based method based on the optimized function) outperformed the Ogino method of
      predicting the next ovulation date. Our method also outperformed the ovulation
      date prediction method that assumes the middle day of a mean menstrual cycle as
      the date of the next ovulation. CONCLUSIONS: The large number of subjects allowed
      us to capture the relationships between the lengths of the menstrual cycle,
      follicular phase, and luteal phase in more detail than previous studies. We then
      demonstrated how the present calendar methods could be improved by the better
      grouping of women. This study suggested that even without integrating various
      biological metrics, the dataset collected by a self-tracking app can be used to
      develop formulas that predict the ovulation day when the data are aggregated.
      Because the method that we developed requires data only on the first day of
      menstruation, it would be the best option for couples during the early stages of
      their attempt to have a baby or for those who want to avoid the cost associated
      with other methods. Moreover, the result will be the baseline for more advanced
      methods that integrate other biological metrics.

PMID- 29180347
TI  - Effectiveness and safety of acupuncture combined with Madopar for Parkinson's
      disease: a systematic review with meta-analysis.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of acupuncture combined with
      Madopar for the treatment of Parkinson's disease (PD), compared to the use of
      Madopar alone. METHODS: A systematic search was carried out for randomised
      controlled trials (RCTs) of acupuncture and Madopar for the treatment of PD
      published between April 1995 and April 2015. The primary outcome was total
      effectiveness rate and secondary outcomes included Unified Parkinson's Disease
      Rating Scale (UPDRS) scores. Data were pooled and analysed with RevMan 5.3.
      Results were expressed as relative ratio (RR) with 95% confidence interval (CIs).
      RESULTS: Finally, 11 RCTs with 831 subjects were included. Meta-analyses showed
      that acupuncture combined with Madopar for the treatment of PD can significantly
      improve the clinical effectiveness compared with Madopar alone (RR=1.28, 95% CI
      1.18 to 1.38, P<0.001). It was also found that acupuncture combined with Madopar
      significantly improved the UPDRS II (SMD=-1.00, 95% CI -1.71 to -0.29, P=0.006)
      and UPDRS I-IV total summed scores (SMD=-1.15, 95% CI -1.63 to -0.67, P<0.001)
      but not UPDRS I (SMD=-0.37, 95% CI -0.77 to 0.02, P=0.06), UPDRS III (SMD=-0.93,
      95% CI -2.28 to 0.41, P=0.17) or UPDRS IV (SMD=-0.78, 95% CI -2.24 to 0.68,
      P=0.30) scores. Accordingly, acupuncture combined with Madopar appeared to have a
      positive effect on activities of daily life and the general condition of patients
      with PD, but was not better than Madopar alone for the treatment of mental
      activity, behaviour, mood and motor disability. In the safety evaluation, it was
      found that acupuncture combined with Madopar was associated with significantly
      fewer adverse effects including gastrointestinal reactions (RR=0.38, 95% CI 0.23
      to 0.65, P<0.001), on-off phenomena (RR=0.27, 95% CI 0.11 to 0.66, P=0.004) and
      mental disorders (RR=0.24, 95% CI 0.06 to 0.92, P=0.04) but did not significantly
      reduce dyskinesia (RR=0.64, 95% CI 0.35 to 1.16, P=0.14). CONCLUSION: Acupuncture
      combined with Madopar appears, to some extent, to improve clinical effectiveness
      and safety in the treatment of PD, compared with Madopar alone. This conclusion
      must be considered cautiously, given the quality of most of the studies included
      was low. Therefore, more high-quality, multicentre, prospective, RCTs with large
      sample sizes are needed to further clarify the effect of acupuncture combined
      with Madopar for PD.

PMID- 29180350
TI  - Undergraduate Performance in Solving Ill-Defined Biochemistry Problems.
AB  - With growing interest in promoting skills related to the scientific process, we
      studied performance in solving ill-defined problems demonstrated by graduating
      biochemistry majors at a public, minority-serving university. As adoption of
      techniques for facilitating the attainment of higher-order learning objectives
      broadens, so too does the need to appropriately measure and understand student
      performance. We extended previous validation of the Individual Problem Solving
      Assessment (IPSA) and administered multiple versions of the IPSA across two
      semesters of biochemistry courses. A final version was taken by majors just
      before program exit, and student responses on that version were analyzed both
      quantitatively and qualitatively. This mixed-methods study quantifies student
      performance in scientific problem solving, while probing the qualitative nature
      of unsatisfactory solutions. Of the five domains measured by the IPSA, we found
      that average graduates were only successful in two areas: evaluating given
      experimental data to state results and reflecting on performance after the
      solution to the problem was provided. The primary difficulties in each domain
      were quite different. The most widespread challenge for students was to design an
      investigation that rationally aligned with a given hypothesis. We also extend the
      findings into pedagogical recommendations.

PMID- 29180348
TI  - Phenotype-genotype spectrum of AAA syndrome from Western India and systematic
      review of literature.
AB  - OBJECTIVE: To study genotype-phenotype spectrum of triple A syndrome (TAS).
      METHODS: Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8)
      and review of genotyped TAS cases reported in world literature (cohort 2, n =
      133, 68 publications). RESULTS: Median age at presentation was 4.75 years (range:
      4-10) and 5 years (range: 1-42) for cohorts 1 and 2, respectively. Alacrima,
      adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen
      in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients
      in cohort 2, respectively. In both cohorts, alacrima was present since birth
      while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC)
      was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site
      mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8
      (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five
      exhibited regional clustering. AI was more prevalent, more often a presenting
      feature, and was diagnosed at younger age in T group (those with truncating
      mutations) as compared to NT (non-truncating mutations) group. ND was more
      prevalent, more common a presenting feature, with later age at onset in NT as
      compared to T group. CONCLUSION: Clinical profile of our patients is similar to
      that of patients worldwide. Alacrima is the earliest and most consistent finding.
      MC deficiency is uncommon. Some recurrent mutations show regional clustering.
      p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our
      cohort. Phenotype of T group differs from that of NT group and merits future
      research.

PMID- 29180351
TI  - Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors and Incident
      Type 2 Diabetes: A Systematic Review and Meta-analysis With Over 96,000 Patient
      Years.
AB  - OBJECTIVE: Like mutations with loss of function in the proprotein convertase
      subtilisin/kexin type 9 (PCSK9) gene, inhibitors of PCSK9 (PCSK9i) may
      potentially favor the manifestation of diabetes. RESEARCH DESIGN AND METHODS: A
      meta-analysis of phase 2/3 randomized clinical trials (RCTs) assessed PCSK9i
      versus placebo in the primary hypercholesterolemia setting. Statins and ezetimibe
      were used in 98.4% of these studies and balanced between PCSK9i and placebo. We
      calculated relative risks (RRs) and 95% CIs using random- and fixed-effect
      models. RESULTS: We included 68,123 participants (20 RCTs) with median follow-up
      of 78 weeks. PCSK9i increased fasting blood glucose (weighted mean difference
      1.88 mg/dL [95% CI 0.91-2.68]; I2 = 0%; P < 0.001) and HbA1c (0.032% [0.011
      0.050]; I2 = 15.5%; P < 0.001) when compared with placebo. This effect was not
      sufficient to increase incidence of diabetes (RR 1.04 [0.96-1.13]; I2 = 0%; P =
      0.427). Exploratory meta-regression analyses indicated an association between the
      increased risk of diabetes and the potency (P = 0.029) and duration (P = 0.026)
      of PCSK9i treatment. CONCLUSIONS: In the short term, PCSK9i therapy favors a
      small but significant increase in plasma glycemia and HbA1c.

PMID- 29180352
TI  - Secondary care doctors denigrate general practice in front of medical students,
      study finds.

PMID- 29180354
TI  - Patients with rare diseases: from therapeutic orphans to pioneers of personalized
      treatments.

PMID- 29180353
TI  - Clec16a, Nrdp1, and USP8 Form a Ubiquitin-Dependent Tripartite Complex That
      Regulates beta-Cell Mitophagy.
AB  - Mitophagy is a cellular quality-control pathway, which is essential for
      elimination of unhealthy mitochondria. While mitophagy is critical to pancreatic
      beta-cell function, the posttranslational signals governing beta-cell
      mitochondrial turnover are unknown. Here, we report that ubiquitination is
      essential for the assembly of a mitophagy regulatory complex, comprised of the E3
      ligase Nrdp1, the deubiquitinase enzyme USP8, and Clec16a, a mediator of beta
      cell mitophagy with unclear function. We discover that the diabetes gene Clec16a
      encodes an E3 ligase, which promotes nondegradative ubiquitin conjugates to
      direct its mitophagy effectors and stabilize the Clec16a-Nrdp1-USP8 complex.
      Inhibition of the Clec16a pathway by the chemotherapeutic lenalidomide, a
      selective ubiquitin ligase inhibitor associated with new-onset diabetes, impairs
      beta-cell mitophagy, oxygen consumption, and insulin secretion. Indeed, patients
      treated with lenalidomide develop compromised beta-cell function. Moreover, the
      beta-cell Clec16a-Nrdp1-USP8 mitophagy complex is destabilized and dysfunctional
      after lenalidomide treatment as well as after glucolipotoxic stress. Thus, the
      Clec16a-Nrdp1-USP8 complex relies on ubiquitin signals to promote mitophagy and
      maintain mitochondrial quality control necessary for optimal beta-cell function.

PMID- 29180356
TI  - Just When We Thought We Knew Everything We Needed To Know about Zn Acquisition
      and Bacterial Pathogenesis.
AB  - It is well established that high-affinity zinc importers play essential roles in
      bacterial virulence, but the studies described by Moreau et al. in this issue (G.
      B. Moreau, A. Qin, and B. J. Mann, J Bacteriol 200:e00587-17, 2018,
      https://doi.org/10.1128/JB.00587-17) demonstrate that we probably still have much
      to learn about how these transporters function and how the genes that encode them
      are regulated in different bacterial pathogens.

PMID- 29180355
TI  - Photoreceptor glucose metabolism determines normal retinal vascular growth.
AB  - The neural cells and factors determining normal vascular growth are not well
      defined even though vision-threatening neovessel growth, a major cause of
      blindness in retinopathy of prematurity (ROP) (and diabetic retinopathy), is
      driven by delayed normal vascular growth. We here examined whether hyperglycemia
      and low adiponectin (APN) levels delayed normal retinal vascularization, driven
      primarily by dysregulated photoreceptor metabolism. In premature infants, low APN
      levels correlated with hyperglycemia and delayed retinal vascular formation.
      Experimentally in a neonatal mouse model of postnatal hyperglycemia modeling
      early ROP, hyperglycemia caused photoreceptor dysfunction and delayed
      neurovascular maturation associated with changes in the APN pathway; recombinant
      mouse APN or APN receptor agonist AdipoRon treatment normalized vascular growth.
      APN deficiency decreased retinal mitochondrial metabolic enzyme levels
      particularly in photoreceptors, suppressed retinal vascular development, and
      decreased photoreceptor platelet-derived growth factor (Pdgfb). APN pathway
      activation reversed these effects. Blockade of mitochondrial respiration
      abolished AdipoRon-induced Pdgfb increase in photoreceptors. Photoreceptor
      knockdown of Pdgfb delayed retinal vascular formation. Stimulation of the APN
      pathway might prevent hyperglycemia-associated retinal abnormalities and suppress
      phase I ROP in premature infants.

PMID- 29180358
TI  - Nonclinical Cardiovascular Studies of Prucalopride, a Highly Selective 5
      Hydroxytryptamine 4 Receptor Agonist.
AB  - Patients with chronic constipation benefit from treatment with 5
      hydroxytryptamine 4 (5-HT4) receptor agonists. However, the first-generation 5
      HT4 receptor agonists cisapride and tegaserod were withdrawn from the market
      owing to rare cardiovascular adverse events that were not 5-HT4-receptor-related
      but due to the lack of selectivity of these drugs. Here we report the nonclinical
      cardiovascular profile of the selective 5-HT4 receptor agonist prucalopride. To
      assess its non-5-HT4 receptor-mediated effects on cardiovascular
      electrophysiological parameters, in vitro studies were performed in human ether-a
      go-go-related gene-transfected cells, guinea pig ventricular myocytes and
      papillary muscle preparations, rabbit and dog Purkinje fibers, and the
      Langendorff rabbit heart. In vivo experiments were performed in a rabbit model
      for drug-induced proarrhythmogenesis, in anesthetized guinea pigs, and
      anesthetized and conscious dogs. In addition, human platelet aggregation and
      coronary artery contraction were studied to exclude interactions that have been
      suggested to mediate the cardiovascular effects of tegaserod. Effects at 5-HT4
      receptors were evaluated in piglet and human atrial myocardium, and in
      anesthetized pigs. Finally, cardiovascular endpoints were investigated in
      chronic, repeated-dose toxicology studies at very high prucalopride doses in rats
      and dogs. No relevant effects were observed in any of the cardiovascular studies
      at concentrations at least 50 times the therapeutic plasma level. Only in pigs
      were minor and transient increases in heart rate and blood pressure noted upon
      first exposure to prucalopride, at plasma levels at least 10 times higher than
      human therapeutic plasma levels. Prucalopride may thus provide therapeutic
      benefit without the cardiovascular risks reported for other 5-HT4 receptor
      agonists.

PMID- 29180357
TI  - Pseudouridine-Free Escherichia coli Ribosomes.
AB  - Pseudouridine (Psi) is present at conserved, functionally important regions in
      the ribosomal RNAs (rRNAs) from all three domains of life. Little, however, is
      known about the functions of Psi modifications in bacterial ribosomes. An
      Escherichia coli strain has been constructed in which all seven rRNA Psi
      synthases have been inactivated and whose ribosomes are devoid of all Psis.
      Surprisingly, this strain displays only minor defects in ribosome biogenesis and
      function, and cell growth is only modestly affected. This is in contrast to a
      strong requirement for Psi in eukaryotic ribosomes and suggests divergent roles
      for rRNA Psi modifications in these two domains.IMPORTANCE Pseudouridine (Psi) is
      the most abundant posttranscriptional modification in RNAs. In the ribosome, Psi
      modifications are typically located at conserved, critical regions, suggesting
      they play an important functional role. In eukarya and archaea, rRNAs are
      modified by a single pseudouridine synthase (PUS) enzyme, targeted to rRNA via a
      snoRNA-dependent mechanism, while bacteria use multiple stand-alone PUS enzymes.
      Disruption of Psi modification of rRNA in eukarya seriously impairs ribosome
      function and cell growth. We have constructed an E. coli multiple deletion strain
      lacking all Psi modifications in rRNA. In contrast to the equivalent eukaryotic
      mutants, the E. coli strain is only modestly affected in growth, decoding, and
      ribosome biogenesis, indicating a differential requirement for Psi modifications
      in these two domains.

PMID- 29180359
TI  - Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid
      Secretion and Motility.
AB  - Tegoprazan [(S)-4-((5,7-difluorochroman-4-yl)oxy)-N,N,2-trimethyl-1H
      benzo[d]imidazole-6-carboxamide], a potassium-competitive acid blocker (P-CAB),
      is a novel potent and highly selective inhibitor of gastric H+/K+-ATPase.
      Tegoprazan inhibited porcine, canine, and human H+/K+-ATPases in vitro with IC50
      values ranging from 0.29 to 0.52 MUM, while that for canine kidney Na+/K+-ATPase
      was more than 100 MUM. A kinetic analysis revealed that tegoprazan inhibited
      H+/K+-ATPase in a potassium-competitive manner and the binding was reversible.
      Oral single administrations of tegoprazan ranging from 0.3 to 30 mg/kg in dogs
      were well absorbed into the blood stream and distributed in gastric tissue/fluid
      higher than in plasma. Tegoprazan potently inhibited histamine-induced gastric
      acid secretion in dogs, and a complete inhibition was observed at 1.0 mg/kg
      starting from 1 hour after administration. Moreover, an oral administration of
      tegoprazan at 1 and 3 mg/kg reversed the pentagastrin-induced acidified gastric
      pH to the neutral range. Interestingly, 3 mg/kg tegoprazan immediately evoked a
      gastric phase III contraction of the migrating motor complex in pentagastrin
      treated dogs and similar effects was observed with the other P-CAB, vonoprazan.
      Tegoprazan is the novel P-CAB that may provide a new option for the therapy of
      gastric acid-related and motility-impaired diseases.

PMID- 29180360
TI  - Production and Biotechnological Potential of Extracellular Polymeric Substances
      from Sponge-Associated Antarctic Bacteria.
AB  - Four sponge-associated Antarctic bacteria (i.e., Winogradskyella sp. strains
      CAL384 and CAL396, Colwellia sp. strain GW185, and Shewanella sp. strain CAL606)
      were selected for the highly mucous appearance of their colonies on agar plates.
      The production of extracellular polymeric substances (EPSs) was enhanced by a
      step-by-step approach, varying the carbon source, substrate and NaCl
      concentrations, temperature, and pH. The EPSs produced under optimal conditions
      were chemically characterized, resulting in a moderate carbohydrate content
      (range, 15 to 28%) and the presence of proteins (range, 3 to 24%) and uronic
      acids (range, 3.2 to 11.9%). Chemical hydrolysis of the carbohydrate portion
      revealed galactose, glucose, galactosamine, and mannose as the principal
      constituents. The potential biotechnological applications of the EPSs were also
      investigated. The high protein content in the EPSs from Winogradskyella sp.
      CAL384 was probably responsible for the excellent emulsifying activity toward
      tested hydrocarbons, with a stable emulsification index (E24) higher than those
      recorded for synthetic surfactants. All the EPSs tested in this work improved the
      freeze-thaw survival ratio of the isolates, suggesting that they may be exploited
      as cryoprotection agents. The addition of a sugar in the culture medium, by
      stimulating EPS production, also allowed isolates to grow in the presence of
      higher concentrations of mercury and cadmium. This finding was probably dependent
      on the presence of uronic acids and sulfate groups, which can act as ligands for
      cations, in the extracted EPSs.IMPORTANCE To date, biological matrices have never
      been employed for the investigation of EPS production by Antarctic
      psychrotolerant marine bacteria. The biotechnological potential of extracellular
      polymeric substances produced by Antarctic bacteria is very broad and comprises
      many advantages, due to their biodegradability, high selectivity, and specific
      action compared to synthetic molecules. Here, several interesting EPS properties
      have been highlighted, such as emulsifying activity, cryoprotection, biofilm
      formation, and heavy metal chelation, suggesting their potential applications in
      cosmetic, environmental, and food biotechnological fields as valid alternatives
      to the commercial polymers currently used.

PMID- 29180361
TI  - Production of 1-Dodecanol, 1-Tetradecanol, and 1,12-Dodecanediol through Whole
      Cell Biotransformation in Escherichia coli.
AB  - Medium- and long-chain 1-alkanol and alpha,omega-alkanediols are used in personal
      care products, in industrial lubricants, and as precursors for polymers
      synthesized for medical applications. The industrial production of alpha,omega
      alkanediols by alkane hydroxylation primarily occurs at high temperature and
      pressure using heavy metal catalysts. However, bioproduction has recently emerged
      as a more economical and environmentally friendly alternative. Among alkane
      monooxygenases, CYP153A from Marinobacter aquaeolei VT8 (CYP153A M.aq ; the
      strain is also known as Marinobacter hydrocarbonoclasticus VT8) possesses low
      overoxidation activity and high regioselectivity and thus has great potential for
      use in terminal hydroxylation. However, the application of CYP153A M.aq is
      limited because it is encoded by a dysfunctional operon. In this study, we
      demonstrated that the operon regulator AlkR M.aq is functional, can be induced by
      alkanes of various lengths, and does not suffer from product inhibition.
      Additionally, we identified a transposon insertion in the CYP153A M.aq operon.
      When the transposon was removed, the expression of the operon genes could be
      induced by alkanes, and the alkanes could then be oxyfunctionalized by the
      resulting proteins. To increase the accessibility of medium- and long-chain
      alkanes, we coexpressed a tunable alkane facilitator (AlkL) from Pseudomonas
      putida GPo1. Using a recombinant Escherichia coli strain, we produced 1.5 g/liter
      1-dodecanol in 20 h and 2 g/liter 1-tetradecanol in 50 h by adding dodecane and
      tetradecane, respectively. Furthermore, in 68 h, we generated 3.76 g/liter of
      1,12-dodecanediol by adding a dodecane-1-dodecanol substrate mixture. This study
      reports a very efficient method of producing C12/C14 alkanols and C12 1,12
      alkanediol by whole-cell biotransformation.IMPORTANCE To produce terminally
      hydroxylated medium- to long-chain alkane compounds by whole-cell
      biotransformation, substrate permeability, enzymatic activity, and the control of
      overoxidability should be considered. Due to difficulties in production, small
      amounts of 1-dodecanol, 1-tetradecanol, and 1,12-dodecanediol are typically
      produced. In this study, we identified an alkane-inducible monooxygenase operon
      that can efficiently catalyze the conversion of alkane to 1-alkanol with no
      detection of the overoxidation product. By coexpressing an alkane membrane
      facilitator, high levels of 1-dodecanol, 1-tetradecanol, and 1,12-dodecanediol
      could be generated. This study is significant for the bioproduction of medium-
      and long-chain 1-alkanol and alpha,omega-alkanediols.

PMID- 29180362
TI  - Limited Effects of Variable-Retention Harvesting on Fungal Communities
      Decomposing Fine Roots in Coastal Temperate Rainforests.
AB  - Fine root litter is the principal source of carbon stored in forest soils and a
      dominant source of carbon for fungal decomposers. Differences in decomposer
      capacity between fungal species may be important determinants of fine-root
      decomposition rates. Variable-retention harvesting (VRH) provides refuge for
      ectomycorrhizal fungi, but its influence on fine-root decomposers is unknown, as
      are the effects of functional shifts in these fungal communities on carbon
      cycling. We compared fungal communities decomposing fine roots (in litter bags)
      under VRH, clear-cut, and uncut stands at two sites (6 and 13 years postharvest)
      and two decay stages (43 days and 1 year after burial) in Douglas fir forests in
      coastal British Columbia, Canada. Fungal species and guilds were identified from
      decomposed fine roots using high-throughput sequencing. Variable retention had
      short-term effects on beta-diversity; harvest treatment modified the fungal
      community composition at the 6-year-postharvest site, but not at the 13-year
      postharvest site. Ericoid and ectomycorrhizal guilds were not more abundant under
      VRH, but stand age significantly structured species composition. Guild
      composition varied by decay stage, with ruderal species later replaced by
      saprotrophs and ectomycorrhizae. Ectomycorrhizal abundance on decomposing fine
      roots may partially explain why fine roots typically decompose more slowly than
      surface litter. Our results indicate that stand age structures fine-root
      decomposers but that decay stage is more important in structuring the fungal
      community than shifts caused by harvesting. The rapid postharvest recovery of
      fungal communities decomposing fine roots suggests resiliency within this
      community, at least in these young regenerating stands in coastal British
      Columbia.IMPORTANCE Globally, fine roots are a dominant source of carbon in
      forest soils, yet the fungi that decompose this material and that drive the
      sequestration or respiration of this carbon remain largely uncharacterized. Fungi
      vary in their capacity to decompose plant litter, suggesting that fungal
      community composition is an important determinant of decomposition rates.
      Variable-retention harvesting is a forestry practice that modifies fungal
      communities by providing refuge for ectomycorrhizal fungi. We evaluated the
      effects of variable retention and clear-cut harvesting on fungal communities
      decomposing fine roots at two sites (6 and 13 years postharvest), at two decay
      stages (43 days and 1 year), and in uncut stands in temperate rainforests.
      Harvesting impacts on fungal community composition were detected only after 6
      years after harvest. We suggest that fungal community composition may be an
      important factor that reduces fine-root decomposition rates relative to those of
      above-ground plant litter, which has important consequences for forest carbon
      cycling.

PMID- 29180363
TI  - Silver Nanoparticles Complexed with Bovine Submaxillary Mucin Possess Strong
      Antibacterial Activity and Protect against Seedling Infection.
AB  - A simple method for the synthesis of nanoparticles (NPs) of silver (Ag) in a
      matrix of bovine submaxillary mucin (BSM) was reported previously by some of the
      authors of this study. Based on mucin characteristics such as long-lasting
      stability, water solubility, and surfactant and adhesive characteristics, we
      hypothesized that these compounds, named BSM-Ag NPs, may possess favorable
      properties as potent antimicrobial agents. The goal of this study was to assess
      whether BSM-Ag NPs possess antibacterial activity, focusing on important plant
      pathogenic bacterial strains representing both Gram-negative (Acidovorax and
      Xanthomonas) and Gram-positive (Clavibacter) genera. Growth inhibition and
      bactericidal assays, as well as electron microscopic observations, demonstrate
      that BSM-Ag NPs, at relatively low concentrations of silver, exert strong
      antimicrobial effects. Moreover, we show that treatment of melon seeds with BSM
      Ag NPs effectively prevents seed-to-seedling transmission of Acidovorax citrulli,
      one of the most threatening pathogens of cucurbit production worldwide. Overall,
      our findings demonstrate strong antimicrobial activity of BSM-Ag NPs and their
      potential application for reducing the spread and establishment of devastating
      bacterial plant diseases in agriculture.IMPORTANCE Bacterial plant diseases
      challenge agricultural production, and the means available to manage them are
      limited. Importantly, many plant-pathogenic bacteria have the ability to colonize
      seeds, and seed-to-seedling transmission is a critical route by which bacterial
      plant diseases spread to new regions and countries. The significance of our study
      resides in the following aspects: (i) the simplicity of the method of BSM-Ag NP
      synthesis, (ii) the advantageous chemical properties of BSM-Ag NPs, (iii) the
      strong antibacterial activity of BSM-Ag NPs at relatively low concentrations of
      silver, and (iv) the fact that, in contrast to most studies on the effects of
      metal NPs on plant pathogens, the proof of concept for the novel compound is
      supported by in planta assays. Application of this technology is not limited to
      agriculture; BSM-Ag NPs potentially could be exploited as a potent antimicrobial
      agent in a wide range of industrial areas, including medicine, veterinary
      medicine, cosmetics, textiles, and household products.

PMID- 29180364
TI  - Genetic Plasticity and Ethylmalonyl Coenzyme A Pathway during Acetate
      Assimilation in Rhodospirillum rubrum S1H under Photoheterotrophic Conditions.
AB  - Purple nonsulfur bacteria represent a promising resource for biotechnology
      because of their great metabolic versatility. Rhodospirillum rubrum has been
      widely studied regarding its metabolism of volatile fatty acid, mainly acetate.
      As the glyoxylate shunt is unavailable in Rs. rubrum, the citramalate cycle
      pathway and the ethylmalonyl-coenzyme A (CoA) pathway are proposed as alternative
      anaplerotic pathways for acetate assimilation. However, despite years of debate,
      neither has been confirmed to be essential. Here, using functional genomics, we
      demonstrate that the ethylmalonyl-CoA pathway is required for acetate
      photoassimilation. Moreover, an unexpected reversible long-term adaptation is
      observed, leading to a drastic decrease in the lag phase characterizing the
      growth of Rs. rubrum in the presence of acetate. Using proteomic and genomic
      analyses, we present evidence that the adaptation phenomenon is associated with
      reversible amplification and overexpression of a 60-kb genome fragment containing
      key enzymes of the ethylmalonyl-CoA pathway. Our observations suggest that a
      genome duplication and amplification phenomenon is not only involved in
      adaptation to acute stress but can also be important for basic carbon metabolism
      and the redox balance.IMPORTANCE Purple nonsulfur bacteria represent a major
      group of anoxygenic photosynthetic bacteria that emerged as a promising resource
      for biotechnology because of their great metabolic versatility and ability to
      grow under various conditions. Rhodospirillum rubrum S1H has notably been
      selected by the European Space Agency to colonize its life support system, called
      MELiSSA, due to its capacity to perform photoheterotrophic assimilation of
      volatile fatty acids (VFAs), mainly acetate. VFAs are valuable carbon sources for
      many applications, combining bioremediation of contaminated environments with the
      generation of added-value products. Acetate is one of the major volatile fatty
      acids generated as a by-product of fermentation processes. In Rs. rubrum, purple
      nonsulfur bacteria, the assimilation of acetate is still under debate since two
      different pathways have been proposed. Here, we clearly demonstrate that the
      ethylmalonyl-CoA pathway is the major anaplerotic pathway for acetate
      assimilation in this strain. Interestingly, we further observed that gene
      duplication and amplification, which represent a well-known phenomenon in
      antibiotic resistance, also play a regulatory function in carbon metabolism and
      redox homeostasis.

PMID- 29180365
TI  - Nutrient co-limited Trichodesmium as nitrogen source or sink in a future ocean.
AB  - Nitrogen-fixing (N2) cyanobacteria provide bioavailable nitrogen to vast ocean
      regions but are in turn limited by iron (Fe) and/or phosphorus (P), which may
      force them to employ alternative nitrogen acquisition strategies. The adaptive
      responses of nitrogen-fixers to global-change drivers under nutrient-limited
      conditions could profoundly alter the current ocean nitrogen and carbon cycles.
      Here, we show that the globally-important N2-fixer Trichodesmium fundamentally
      shifts nitrogen metabolism towards organic-nitrogen scavenging following long
      term high-CO2 adaptation under iron and/or phosphorus (co)-limitation. Global
      shifts in transcripts and proteins under high CO2/Fe-limited and/or P-limited
      conditions include decreases in the N2-fixing nitrogenase enzyme, coupled with
      major increases in enzymes that oxidize trimethylamine (TMA). TMA is an abundant,
      biogeochemically-important organic nitrogen compound that supports rapid
      Trichodesmium growth while inhibiting N2 fixation. In a future high-CO2 ocean,
      this whole-cell energetic reallocation towards organic nitrogen scavenging and
      away from N2-fixation may reduce new-nitrogen inputs by Trichodesmium, while
      simultaneously depleting the scarce fixed-nitrogen supplies of nitrogen-limited
      open ocean ecosystems.ImportanceTrichodesmium is among the most biogeochemically
      significant microorganisms in the ocean, since it supplies up to 50% of the new
      nitrogen supporting open ocean food webs. We used Trichodesmium cultures adapted
      to high CO2 for 7 years followed by additional exposure to iron and/or phosphorus
      (co)-limitation. We show that 'future ocean' conditions of high CO2 and
      concurrent nutrient limitation(s) fundamentally shift nitrogen metabolism away
      from nitrogen fixation, and instead towards upregulation of organic-nitrogen
      scavenging pathways. We show that Trichodesmium's responses to projected future
      ocean conditions include decreases in the nitrogen-fixing nitrogenase enzymes,
      coupled with major increases in enzymes that oxidize the abundant organic
      nitrogen source trimethylamine (TMA). Such a shift towards organic nitrogen
      uptake and away from nitrogen fixation may substantially reduce new-nitrogen
      inputs by Trichodesmium to the rest of the microbial community in the future high
      CO2 ocean, with potential global implications for ocean carbon and nitrogen
      cycling.

PMID- 29180366
TI  - In Vitro Enzymatic Depolymerization of Lignin with Release of Syringyl, Guaiacyl,
      and Tricin Units.
AB  - New environmentally sound technologies are needed to derive valuable compounds
      from renewable resources. Lignin, an abundant polymer in terrestrial plants
      comprised predominantly of guaiacyl and syringyl monoaromatic phenylpropanoid
      units, is a potential natural source of aromatic compounds. In addition, the
      plant secondary metabolite tricin is a recently discovered and moderately
      abundant flavonoid in grasses. The most prevalent interunit linkage between
      guaiacyl, syringyl, and tricin units is the beta-ether linkage. Previous studies
      have shown that bacterial beta-etherase pathway enzymes catalyze glutathione
      dependent cleavage of beta-ether bonds in dimeric beta-ether lignin model
      compounds. To date, however, it remains unclear whether the known beta-etherase
      enzymes are active on lignin polymers. Here we report on enzymes that catalyze
      beta-ether cleavage from bona fide lignin, under conditions that recycle the
      cosubstrates NAD+ and glutathione. Guaiacyl, syringyl, and tricin derivatives
      were identified as reaction products when different model compounds or lignin
      fractions were used as substrates. These results demonstrate an in vitro
      enzymatic system that can recycle cosubstrates while releasing aromatic monomers
      from model compounds as well as natural and engineered lignin oligomers. These
      findings can improve the ability to produce valuable aromatic compounds from a
      renewable resource like lignin.IMPORTANCE Many bacteria are predicted to contain
      enzymes that could convert renewable carbon sources into substitutes for
      compounds that are derived from petroleum. The beta-etherase pathway present in
      sphingomonad bacteria could cleave the abundant beta-O-4-aryl ether bonds in
      plant lignin, releasing a biobased source of aromatic compounds for the chemical
      industry. However, the activity of these enzymes on the complex aromatic
      oligomers found in plant lignin is unknown. Here we demonstrate biodegradation of
      lignin polymers using a minimal set of beta-etherase pathway enzymes, the ability
      to recycle needed cofactors (glutathione and NAD+) in vitro, and the release of
      guaiacyl, syringyl, and tricin as depolymerized products from lignin. These
      observations provide critical evidence for the use and future optimization of
      these bacterial beta-etherase pathway enzymes for industrial-level
      biotechnological applications designed to derive high-value monomeric aromatic
      compounds from lignin.

PMID- 29180367
TI  - GH30 Glucuronoxylan-Specific Xylanase from Streptomyces turgidiscabies C56.
AB  - Endoxylanases are important enzymes in bioenergy research because they
      specifically hydrolyze xylan, the predominant polysaccharide in the hemicellulose
      fraction of lignocellulosic biomass. For effective biomass utilization, it is
      important to understand the mechanism of substrate recognition by these enzymes.
      Recent studies have shown that the substrate specificities of bacterial and
      fungal endoxylanases classified into glycoside hydrolase family 30 (GH30) were
      quite different. While the functional differences have been described, the
      mechanism of substrate recognition is still unknown. Therefore, a gene encoding a
      putative GH30 endoxylanase was cloned from Streptomyces turgidiscabies C56, and
      the recombinant enzyme was purified and characterized. GH30 glucuronoxylan
      specific xylanase A of Streptomyces turgidiscabies (StXyn30A) showed hydrolytic
      activity with xylans containing both glucuronic acid and the more common 4-O
      methyl-glucuronic acid side-chain substitutions but not on linear
      xylooligosaccharides, suggesting that this enzyme requires the recognition of
      glucuronic acid side chains for hydrolysis. The StXyn30A limit product structure
      was analyzed following a secondary beta-xylosidase treatment by thin-layer
      chromatography and mass spectrometry analysis. The hydrolysis products from both
      glucuronoxylan and 4-O-methylglucuronoxylan by StXyn30A have these main-chain
      substitutions on the second xylopyranosyl residue from the reducing end. Because
      previous structural studies of bacterial GH30 enzymes and molecular modeling of
      StXyn30A suggested that a conserved arginine residue (Arg296) interacts with the
      glucuronic acid side-chain carboxyl group, we focused on this residue, which is
      conserved at subsite -2 of bacterial but not fungal GH30 endoxylanases. To help
      gain an understanding of the mechanism of how StXyn30A recognizes glucuronic acid
      substitutions, Arg296 mutant enzymes were studied. The glucuronoxylan hydrolytic
      activities of Arg296 mutants were significantly reduced in comparison to those of
      the wild-type enzyme. Furthermore, limit products other than aldotriouronic acid
      were observed for these Arg296 mutants upon secondary beta-xylosidase treatment.
      These results indicate that a disruption of the highly conserved Arg296
      interaction leads to a decrease of functional specificity in StXyn30A, as
      indicated by the detection of alternative hydrolysis products. Our studies allow
      a better understanding of the mechanism of glucuronoxylan recognition and enzyme
      specificity by bacterial GH30 endoxylanases and provide further definition of
      these unique enzymes for their potential application in industry.IMPORTANCE
      Hemicellulases are important enzymes that hydrolyze hemicellulosic
      polysaccharides to smaller sugars for eventual microbial assimilation and
      metabolism. These hemicellulases include endoxylanases that cleave the beta-1,4
      xylose main chain of xylan, the predominant form of hemicellulose in
      lignocellulosic biomass. Endoxylanases play an important role in the utilization
      of plant biomass because in addition to their general utility in xylan
      degradation, they can also be used to create defined compositions of
      xylooligosaccharides. For this, it is important to understand the mechanism of
      substrate recognition. Recent studies have shown that the substrate specificities
      of bacterial and fungal endoxylanases that are classified into glycoside
      hydrolase family 30 (GH30) were distinct, but the difference in the mechanisms of
      substrate recognition is still unknown. We performed characterization and
      mutagenesis analyses of a new bacterial GH30 endoxylanase for comparison with
      previously reported fungal GH30 endoxylanases. Our study results in a better
      understanding of the mechanism of substrate specificity and recognition for
      bacterial GH30 endoxylanases. The experimental approach and resulting data
      support the conclusions and provide further definition of the structure and
      function of GH30 endoxylanases for their application in bioenergy research.

PMID- 29180368
TI  - Impact of Peat Mining and Restoration on Methane Turnover Potential and Methane
      Cycling Microorganisms in a Northern Bog.
AB  - Ombrotrophic peatlands are a recognized global carbon reservoir. Without
      restoration and peat regrowth, harvested peatlands are dramatically altered,
      impairing their carbon sink function, with consequences for methane turnover.
      Previous studies determined the impact of commercial mining on the
      physicochemical properties of peat and the effects on methane turnover. However,
      the response of the underlying microbial communities catalyzing methane
      production and oxidation have so far received little attention. We hypothesize
      that with the return of Sphagnum spp. postharvest, methane turnover potential and
      the corresponding microbial communities will converge in a natural and restored
      peatland. To address our hypothesis, we determined the potential methane
      production and oxidation rates in natural (as a reference), actively mined,
      abandoned, and restored peatlands over two consecutive years. In all sites, the
      methanogenic and methanotrophic population sizes were enumerated using
      quantitative PCR (qPCR) assays targeting the mcrA and pmoA genes, respectively.
      Shifts in the community composition were determined using Illumina MiSeq
      sequencing of the mcrA gene and a pmoA-based terminal restriction fragment length
      polymorphism (t-RFLP) analysis, complemented by cloning and sequence analysis of
      the mmoX gene. Peat mining adversely affected methane turnover potential, but the
      rates recovered in the restored site. The recovery in potential activity was
      reflected in the methanogenic and methanotrophic abundances. However, the
      microbial community composition was altered, being more pronounced for the
      methanotrophs. Overall, we observed a lag between the recovery of the
      methanogenic/methanotrophic activity and the return of the corresponding
      microbial communities, suggesting that a longer duration (>15 years) is needed to
      reverse mining-induced effects on the methane-cycling microbial
      communities.IMPORTANCE Ombrotrophic peatlands are a crucial carbon sink, but this
      environment is also a source of methane, an important greenhouse gas. Methane
      emission in peatlands is regulated by methane production and oxidation catalyzed
      by methanogens and methanotrophs, respectively. Methane-cycling microbial
      communities have been documented in natural peatlands. However, less is known of
      their response to peat mining and of the recovery of the community after
      restoration. Mining exerts an adverse impact on potential methane production and
      oxidation rates and on methanogenic and methanotrophic population abundances.
      Peat mining also induced a shift in the methane-cycling microbial community
      composition. Nevertheless, with the return of Sphagnum spp. in the restored site
      after 15 years, methanogenic and methanotrophic activity and population abundance
      recovered well. The recovery, however, was not fully reflected in the community
      composition, suggesting that >15 years are needed to reverse mining-induced
      effects.

PMID- 29180369
TI  - Membrane Vesicles Derived from Bordetella bronchiseptica: Active Constituent of a
      New Vaccine against Infections Caused by This Pathogen.
AB  - Bordetella bronchiseptica, a Gram-negative bacterium, causes chronic respiratory
      tract infections in a wide variety of mammalian hosts, including humans (albeit
      rarely). We recently designed Bordetella pertussis and Bordetella parapertussis
      experimental vaccines based on outer membrane vesicles (OMVs) derived from each
      pathogen, and we obtained protection against the respective infections in mice.
      Here, we demonstrated that OMVs derived from virulent-phase B. bronchiseptica
      (OMVBbvir+) protected mice against sublethal infections with different B.
      bronchiseptica strains, two isolated from farm animals and one isolated from a
      human patient. In all infections, we observed that the B. bronchiseptica loads
      were significantly reduced in the lungs of vaccinated animals; the lung-recovered
      CFU were decreased by >=4 log units, compared with those detected in the lungs of
      nonimmunized animals (P < 0.001). In the OMVBbvir+-immunized mice, we detected
      IgG antibody titers against B. bronchiseptica whole-cell lysates, along with an
      immune serum having bacterial killing activity that both recognized B.
      bronchiseptica lipopolysaccharides and polypeptides such as GroEL and outer
      membrane protein C (OMPc) and demonstrated an essential protective capacity
      against B. bronchiseptica infection, as detected by passive in vivo transfer
      experiments. Stimulation of cultured splenocytes from immunized mice with
      OMVBbvir+ resulted in interleukin 5 (IL-5), gamma interferon (IFN-gamma), and IL
      17 production, indicating that the vesicles induced mixed Th2, Th1, and Th17 T
      cell immune responses. We detected, by adoptive transfer assays, that spleen
      cells from OMVBbvir+-immunized mice also contributed to the observed protection
      against B. bronchiseptica infection. OMVs from avirulent-phase B. bronchiseptica
      and the resulting induced immune sera were also able to protect mice against B.
      bronchiseptica infection.IMPORTANCEBordetella bronchiseptica, a Gram-negative
      bacterium, causes chronic respiratory tract infections in a wide variety of
      mammalian hosts, including humans (albeit rarely). Several vaccines aimed at
      preventing B. bronchiseptica infection have been developed and used, but a safe
      effective vaccine is still needed. The significance and relevance of our research
      lie in the characterization of the OMVs derived from B. bronchiseptica as the
      source of a new experimental vaccine. We demonstrated here that our formulation
      based on OMVs derived from virulent-phase B. bronchiseptica (OMVBbvir+) was
      effective against infections caused by B. bronchiseptica isolates obtained from
      different hosts (farm animals and a human patient). In vitro and in vivo
      characterization of humoral and cellular immune responses induced by the
      OMVBbvir+ vaccine enabled a better understanding of the mechanism of protection
      necessary to control B. bronchiseptica infection. Here we also demonstrated that
      OMVs derived from B. bronchiseptica in the avirulent phase and the corresponding
      induced humoral immune response were able to protect mice from B. bronchiseptica
      infection. This realization provides the basis for the development of novel
      vaccines not only against the acute stages of the disease but also against stages
      of the disease or the infectious cycle in which avirulence factors could play a
      role.

PMID- 29180370
TI  - Quantifying the Survival of Multiple Salmonella enterica Serovars in vivo using
      Massively-parallel Whole Genome Sequencing to Predict Zoonotic Risk.
AB  - Salmonella enterica is an animal and zoonotic pathogen of worldwide importance.
      Serovars exist that differ in their host and tissue tropism. Cattle are an
      important reservoir of human non-typhoidal salmonellosis and contaminated bovine
      peripheral lymph nodes enter the food chain via ground beef. The relative ability
      of different serovars to survive within the bovine lymphatic system is poorly
      understood and constrains the development of control strategies. This problem was
      addressed by developing a massively-parallel whole genome sequencing method to
      study mixed-serovar infections in vivoSalmonella serovars differ genetically by
      naturally occurring single nucleotide polymorphisms (SNPs) in certain genes. It
      was hypothesised that these SNPs could be used as markers to simultaneously
      identify serovars in mixed populations and quantify the abundance of each member
      in a population. The performance of the method was validated in vitro using
      simulated pools containing up to 11 serovars in varying proportions. It was then
      applied to study serovar survival in vivo in cattle challenged orally with the
      same 11 serovars. All the serovars successfully colonised the bovine lymphatic
      system, including the peripheral lymph nodes, and thus pose a similar risk of
      zoonosis. This method enables the fate of multiple genetically unmodified strains
      to be evaluated simultaneously in a single animal. It could be useful in reducing
      the number of animals required to study multi-strain infections and for testing
      the cross-protective efficacy of vaccines and treatments. It also has the
      potential to be applied to diverse bacterial species which possess shared but
      polymorphic alleles.Importance While some Salmonella serovars are more frequently
      isolated from lymph nodes rather than the faeces and environment of cattle, the
      relative ability of serovars to survive within the lymphatic system of cattle
      remains ill-defined. A sequencing-based method was developed, which used
      available information from sequenced Salmonella genomes to study the dynamics of
      mixed-serovar infections in vivo The main advantages of the method include the
      simultaneous identification and quantification of multiple strains without any
      genetic modification and minimal animal use. This approach could be used in
      vaccination trials or in epidemiological surveys where an understanding of the
      dynamics of closely-related strains of a pathogen in mixed populations could
      inform the prediction of zoonotic risk and the development of intervention
      strategies.

PMID- 29180371
TI  - Ankyrin-Like Protein AnkB Interacts with CatB, Affects Catalase Activity, and
      Enhances Resistance of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv.
      oryzicola to Phenazine-1-Carboxylic Acid.
AB  - Xanthomonas oryzae pv. oryzae, which causes rice bacterial leaf blight, and
      Xanthomonas oryzae pv. oryzicola, which causes rice bacterial leaf streak, are
      important plant-pathogenic bacteria. A member of the adaptor protein family,
      ankyrin protein, has been investigated largely in humans but rarely in plant
      pathogenic bacteria. In this study, a novel ankyrin-like protein, AnkB, was
      identified in X. oryzae pv. oryzae and X. oryzae pv. oryzicola. The expression of
      ankB was significantly upregulated when these bacteria were treated with
      phenazine-1-carboxylic acid (PCA). ankB is located 58 bp downstream of the gene
      catB (which encodes a catalase) in both bacteria, and the gene expression of catB
      and catalase activity were reduced following ankB deletion in X. oryzae pv.
      oryzae and X. oryzae pv. oryzicola. Furthermore, we demonstrated that AnkB
      directly interacts with CatB by glutathione S-transferase (GST) pulldown assays.
      Deletion of ankB increased the sensitivity of X. oryzae pv. oryzae and X. oryzae
      pv. oryzicola to H2O2 and PCA, decreased bacterial biofilm formation, swimming
      ability, and exopolysaccharide (EPS) production, and also reduced virulence on
      rice. Together our results indicate that the ankyrin-like protein AnkB has
      important and conserved roles in antioxidant systems and pathogenicity in X.
      oryzae pv. oryzae and X. oryzae pv. oryzicola.IMPORTANCE This study demonstrates
      that the ankyrin protein AnkB directly interacts with catalase CatB in
      Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola. Ankyrin
      protein AnkB can affect the gene expression of catB, catalase activity, and
      sensitivity to H2O2 In Xanthomonas spp., the locations of genes ankB and catB and
      the amino acid sequence of AnkB are highly conserved. It is suggested that in
      prokaryotes, AnkB plays a conserved role in the defense against oxidative stress.

PMID- 29180372
TI  - Quality of Irrigation Water Affects Soil Functionality and Bacterial Community
      Stability in Response to Heat Disturbance.
AB  - Anthropogenic activities alter the structure and function of a bacterial
      community. Furthermore, bacterial communities structured by the conditions the
      anthropogenic activities present may consequently reduce their stability in
      response to an unpredicted acute disturbance. The present mesocosm-scale study
      exposed soil bacterial communities to different irrigation water types, including
      freshwater, fertilized freshwater, treated wastewater, and artificial wastewater,
      and evaluated their response to a disturbance caused by heat. These effectors may
      be considered deterministic and stochastic forces common in agricultural
      operations of arid and semiarid regions. Bacterial communities under conditions
      of high mineral and organic carbon availability (artificial wastewater) differed
      from the native bacterial community and showed a proteobacterial dominance. These
      bacterial communities had a lower resistance to the heat treatment disturbance
      than soils under conditions of low resource availability (high-quality treated
      wastewater or freshwater). The latter soil bacterial communities showed a higher
      abundance of operational taxonomic units (OTUs) classified as Bacilli These
      results were elucidated by soil under conditions of high resource availability,
      which lost higher degrees of functional potential and had a greater bacterial
      community composition change. However, the functional resilience, after the
      disturbance ended, was higher under a condition of high resource availability
      despite the bacterial community composition shift and the decrease in species
      richness. The functional resilience was directly connected to the high growth
      rates of certain Bacteroidetes and proteobacterial groups. A high stability was
      found in samples that supported the coexistence of both resistant OTUs and fast
      growing OTUs.IMPORTANCE This report presents the results of a study employing a
      hypothesis-based experimental approach to reveal the forces involved in
      determining the stability of a soil bacterial community to disturbance. The
      resultant postdisturbance bacterial community composition dynamics and
      functionality were analyzed. The paper demonstrates the relatedness of community
      structure and stability under cultivation conditions prevalent in an arid area
      under irrigation with water of different qualities. The use of common
      agricultural practices to demonstrate these features has not been described
      before. The combination of a fundamental theoretical issue in ecology with common
      and concerning disturbances caused by agricultural practice makes this study
      unique. Furthermore, the results of the present study have applicable importance
      regarding soil conservation, as it enables a better characterization and
      monitoring of stressed soil bacterial communities and possible intervention to
      reduce the stress. It will also be of valued interest in coming years, as fresh
      water scarcity and the use of alternative water sources are expected to rise
      globally.

PMID- 29180373
TI  - Generation of Bacteriophage-Insensitive Mutants of Streptococcus thermophilus via
      an Antisense RNA CRISPR-Cas Silencing Approach.
AB  - Predation of starter lactic acid bacteria such as Streptococcus thermophilus by
      bacteriophages is a persistent and costly problem in the dairy industry. CRISPR
      mediated bacteriophage insensitive mutants (BIMs), while straightforward to
      generate and verify, can quickly be overcome by mutant phages. The aim of this
      study was to develop a tool allowing the generation of derivatives of commercial
      S. thermophilus strains which are resistant to phage attack through a non-CRISPR
      mediated mechanism, with the objective of generating BIMs exhibiting stable
      resistance against a range of isolated lytic S. thermophilus phages. To achieve
      this, standard BIM generation was complemented by the use of the wild-type (WT)
      strain which had been transformed with an antisense mRNA-generating plasmid
      (targeting a crucial CRISPR-associated [cas] gene) in order to facilitate the
      generation of non-CRISPR-mediated BIMs. Phage sensitivity assays suggest that non
      CRISPR-mediated BIMs exhibit some advantages compared to CRISPR-mediated BIMs
      derived from the same strain.IMPORTANCE The outlined approach reveals the
      presence of a powerful host-imposed barrier for phage infection in S.
      thermophilus Considering the detrimental economic consequences of phage infection
      in the dairy processing environment, the developed methodology has widespread
      applications, particularly where other methods may not be practical or effective
      in obtaining robust, phage-tolerant S. thermophilus starter strains.

PMID- 29180375
TI  - Formation and Characterization of Early Bacterial Biofilms on Different Wood
      Typologies Applied in Dairy Production.
AB  - The main hypothesis of this work was that Sicilian forestry resources are
      suitable for the production of equipment to be used in cheese making and
      indigenous milk lactic acid bacteria (LAB) are able to develop stable biofilms
      providing starter and nonstarter cultures necessary for curd fermentation and
      cheese ripening, respectively. Hence, the present work was carried out with
      deproteinized whey to evaluate LAB biofilm formation on different woods derived
      from tree species grown in Sicily. Microbiological and scanning electron
      microscopy analyses showed minimal differences in microbial levels and
      compositions for the neoformed biofilms. The specific investigation of Salmonella
      spp., Listeria monocytogenes, Escherichia coli, coagulase-positive staphylococci
      (CPS), and sulfite-reducing anaerobes did not generate any colony for all vats
      before and after bacterial adhesion. LAB populations dominated all vat surfaces.
      The highest levels (7.63 log CFU/cm2) were registered for thermophilic cocci.
      Different colonies were characterized physiologically, biochemically, and
      genetically (at strain and species levels). Six species within the genera
      Enterococcus, Lactobacillus, Lactococcus, and Streptococcus were identified. The
      species most frequently present were Lactobacillus fermentum and Lactococcus
      lactis LAB found on the surfaces of the wooden vats in this study showed
      interesting characteristics important for dairy manufacture. To thoroughly
      investigate the safety of the wooden vat, a test of artificial contamination on
      new Calabrian chestnut (control wood) vats was carried out. The results showed
      that LAB represent efficient barriers to the adhesion of the main dairy
      pathogens, probably due to their acidity and bacteriocin generation.IMPORTANCE
      This study highlights the importance of using wooden vats for traditional cheese
      production and provides evidence for the valorization of the Sicilian forest wood
      resources via the production of dairy equipment.

PMID- 29180374
TI  - Diazotroph Community Characterization via a High-Throughput nifH Amplicon
      Sequencing and Analysis Pipeline.
AB  - The dinitrogenase reductase gene (nifH) is the most widely established molecular
      marker for the study of nitrogen-fixing prokaryotes in nature. A large number of
      PCR primer sets have been developed for nifH amplification, and the effective
      deployment of these approaches should be guided by a rapid, easy-to-use analysis
      protocol. Bioinformatic analysis of marker gene sequences also requires
      considerable expertise. In this study, we advance the state of the art for nifH
      analysis by evaluating nifH primer set performance, developing an improved
      amplicon sequencing workflow, and implementing a user-friendly bioinformatics
      pipeline. The developed amplicon sequencing workflow is a three-stage PCR-based
      approach that uses established technologies for incorporating sample-specific
      barcode sequences and sequencing adapters. Based on our primer evaluation, we
      recommend the Ando primer set be used with a modified annealing temperature of 58
      degrees C, as this approach captured the largest diversity of nifH templates,
      including paralog cluster IV/V sequences. To improve nifH sequence analysis, we
      developed a computational pipeline which infers taxonomy and optionally filters
      out paralog sequences. In addition, we employed an empirical model to derive
      optimal operational taxonomic unit (OTU) cutoffs for the nifH gene at the
      species, genus, and family levels. A comprehensive workflow script named TaxADivA
      (TAXonomy Assignment and DIVersity Assessment) is provided to ease processing and
      analysis of nifH amplicons. Our approach is then validated through
      characterization of diazotroph communities across environmental gradients in
      beach sands impacted by the Deepwater Horizon oil spill in the Gulf of Mexico, in
      a peat moss-dominated wetland, and in various plant compartments of a sugarcane
      field.IMPORTANCE Nitrogen availability often limits ecosystem productivity, and
      nitrogen fixation, exclusive to prokaryotes, comprises a major source of nitrogen
      input that sustains food webs. The nifH gene, which codes for the iron protein of
      the nitrogenase enzyme, is the most widely established molecular marker for the
      study of nitrogen-fixing microorganisms (diazotrophs) in nature. In this study, a
      flexible sequencing/analysis pipeline, named TaxADivA, was developed for nifH
      amplicons produced by Illumina paired-end sequencing, and it enables an inference
      of taxonomy, performs clustering, and produces output in formats that may be used
      by programs that facilitate data exploration and analysis. Diazotroph diversity
      and community composition are linked to ecosystem functioning, and our results
      advance the phylogenetic characterization of diazotroph communities by providing
      empirically derived nifH similarity cutoffs for species, genus, and family
      levels. The utility of our pipeline is validated for diazotroph communities in a
      variety of ecosystems, including contaminated beach sands, peatland ecosystems,
      living plant tissues, and rhizosphere soil.

PMID- 29180376
TI  - Brexit and wage caps are blamed for UK doctor and nurse shortage.

PMID- 29180377
TI  - Comparison of Canadian public medication insurance plans and the impact on out-of
      pocket costs.
AB  - BACKGROUND: Research from 2006 documented substantial variation in medication
      coverage for residents across Canada. Since then, some provinces have implemented
      major medication plan reforms. We aimed to update the information on publicly
      funded medication insurance plans available across Canada and to compare out-of
      pocket costs across the country. METHODS: We compared provincial medication
      insurance plans using data from public websites and other public source
      documents. Using 2 hypothetical clinical examples, we determined the amount and
      type of a patient's out-of-pocket costs for 5 different patient subtypes that
      varied based on medication burden, age and income. RESULTS: Each province offers
      a plan to all residents. Cost-sharing is employed across all provinces. Some
      residents must pay a premium to receive insurance or must pay 100% of their
      medication costs until they reach a deductible amount, above which government
      funding covers a portion of medication costs. With the scenario of low medication
      burden (medication cost about $500), out-of-pocket costs ranged from $250 to
      $2100 for higher-income residents and from $0 to $700 for lower-income residents.
      With the scenario of high medication burden (medication cost about $1800), the
      corresponding ranges were $250-$2500 and $0-$1100. The variation was due to
      province of residence, age and income. INTERPRETATION: Variations in out-of
      pocket payments continue to exist across the provinces, with some groups facing
      high expenses. Further work is required to understand the impact of different
      cost-sharing mechanisms, develop policies to limit out-of-pocket expenses and
      improve provincial drug plans.

PMID- 29180378
TI  - Cationic gas-filled microbubbles for ultrasound-based nucleic acids delivery.
AB  - The use of ultrasound has gained great interest for nucleic acids delivery.
      Ultrasound can reach deep tissues in non-invasive manner. The process of
      sonoporation is based on the use of low-frequency ultrasound combined with gas
      filled microbubbles (MBs) allowing an improved delivery of molecules including
      nucleic acids in the insonified tissue. For in vivo gene transfer, the
      engineering of cationic MBs is essential for creating strong electrostatic
      interactions between MBs and nucleic acids leading to their protection against
      nucleases degradation and high concentration within the target tissue. Cationic
      MBs must be stable enough to withstand nucleic acids interaction, have a good
      size distribution for in vivo administration, and enough acoustic activity to be
      detected by echography. This review aims to summarize the basic principles of
      ultrasound-based delivery and new knowledge acquired in these recent years about
      this method. A focus is made on gene delivery by discussing reported studies made
      with cationic MBs including ours. They have the ability for efficient delivery of
      plasmid DNA (pDNA), mRNA or siRNA. Last, we discuss about the key challenges that
      have to be faced for a fine use of this delivery system.

PMID- 29180379
TI  - Selection of internal references for qRT-PCR assays of human hepatocellular
      carcinoma cell lines.
AB  - Selecting internal references is important for normalizing the loading quantity
      of samples in quantitative reverse-transcription PCR (qRT-PCR). In the present
      study, a systematic evaluation of reference genes among nine hepatocellular
      carcinoma (HCC) cell lines was conducted. After screening the microarray assay
      data of ten HCC cell lines, 19 candidate reference genes were preselected and
      then evaluated by qRT-PCR, together with ACTB, GAPDH, HPRT1 and TUBB The
      expression evenness of these candidate genes was evaluated using RefFinder. The
      stabilities of the reference genes were further evaluated under different
      experimental perturbations in Huh-7 and MHCC-97L, and the applicability of the
      reference genes was assessed by measuring the mRNA expression of CCND1, CCND3,
      CDK4 and CDK6 under sorafenib treatment in Huh-7. Results showed that TFG and
      SFRS4 are among the most reliable reference genes, and ACTB ranks third and acts
      quite well as a classical choice, whereas GAPDH, HPRT1 and TUBB are not proper
      reference genes in qRT-PCR assays among the HCC cell lines. SFRS4, YWHAB, SFRS4
      and CNPY3 are the most stable reference genes of the MHCC-97L under the
      perturbations of chemotherapy, oxidative stress, starvation and hypoxia
      respectively, whereas YWHAB is the most stable one of Huh-7 under all
      perturbations. GAPDH is recommended as a reference gene under chemotherapy
      perturbations. YWHAB and UBE2B, TMED2 and TSFM, and GAPDH and TSFM are the two
      best reference genes under oxidative stress, starvation and hypoxia perturbations
      respectively. TSFM is stable in both cell lines across all the perturbations.

PMID- 29180380
TI  - OsmiR396d Affects Gibberellin and Brassinosteroid Signaling to Regulate Plant
      Architecture in Rice.
AB  - Genetic improvement of plant architecture is one of the strategies for increasing
      the yield potential of rice (Oryza sativa). Although great progress has been made
      in the understanding of plant architecture regulation, the precise mechanism is
      still an urgent need to be revealed. Here, we report that over-expression of
      OsMIR396d in rice results in semidwarf and increased leaf angle, a typical
      phenotype of brassinosteroid (BR) enhanced mutant. OsmiR396d is involved in the
      interaction network of BR and gibberellin (GA) signaling. In OsMIR396d over
      expression plants, BR signaling was enhanced. In contrast, both the signaling and
      biosynthesis of GA were impaired. BRASSINAZOLE-RESISTANT1, a core transcription
      activator of BR signaling, directly promoted the accumulation of OsmiR396d, which
      controlled BR response and GA biosynthesis by regulating the expression of
      different target genes respectively. GROWTH REGULATING FACTOR 6, one of OsmiR396d
      targets, participated in GA biosynthesis and signal transduction but was not
      directly involved in BR signaling. This study provides a new insight into the
      understanding of interaction between BR and GA from multiple levels on
      controlling plant architecture.

PMID- 29180382
TI  - What to do about the Canadian Resident Matching Service.

PMID- 29180381
TI  - Extracellular ATP Acts on Jasmonate Signaling to Reinforce Plant Defense.
AB  - Damaged cells send various signals to stimulate defense responses. Recent
      identification and genetic studies of the plant purinoceptor, P2K1 (also known as
      DORN1), have demonstrated that extracellular ATP is a signal involved in plant
      stress responses, including wounding, perhaps to evoke plant defense. However, it
      remains largely unknown how extracellular ATP induces plant defense responses.
      Here, we demonstrate that extracellular ATP induces plant defense mediated
      through activation of the intracellular signaling of jasmonate (JA), a well
      characterized defense hormone. In Arabidopsis (Arabidopsis thaliana) leaves, ATP
      pretreatment induced resistance against the necrotrophic fungus, Botrytis cinerea
      The induced resistance was enhanced in the P2K1 receptor overexpression line, but
      reduced in the receptor mutant, dorn1-3 Mining the transcriptome data revealed
      that ATP induces a set of JA-induced genes. In addition, the P2K1-associated
      coexpression network contains defense-related genes, including those encoding
      jasmonate ZIM-domain (JAZ) proteins, which play key roles as repressors of JA
      signaling. We examined whether extracellular ATP impacts the stability of JAZ1 in
      Arabidopsis. The results showed that the JAZ1 stability decreased in response to
      ATP addition in a proteasome-dependent manner. This reduction required
      intracellular signaling via second messengers-cytosolic calcium, reactive oxygen
      species, and nitric oxide. Interestingly, the ATP-induced JAZ1 degradation was
      attenuated in the JA receptor mutant, coi1, but not in the JA biosynthesis
      mutant, aos, or upon addition of JA biosynthesis inhibitors. Immunoprecipitation
      analysis demonstrated that ATP increases the interaction between COI1 and JAZ1,
      suggesting direct cross talk between extracellular ATP and JA in intracellular
      signaling events. Taken together, these results suggest that extracellular ATP
      signaling directly impacts the JA signaling pathway to maximize plant defense
      responses.

PMID- 29180383
TI  - Comparative risk of incident venous thromboembolism in patients with inflammatory
      bowel disease initiating tumour necrosis factor-alpha inhibitors or nonbiologic
      agents: a cohort study.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) increases the risk of venous
      thromboembolism (VTE) by 2 to 3 times. We compared the reduction in risk of
      incident VTE associated with use of tumour necrosis factor-alpha (TNF-alpha)
      inhibitors versus nonbiologic immunomodulatory agents in patients with IBD.
      METHODS: This observational cohort study used data from public (Medicaid, 2000
      2010; Medicare, 2007-2013) and private (Optum Clinformatics, 2004-2013) health
      insurance programs in the United States. We included a total of 21 671 patients
      who had IBD without a prior diagnosis of cancer or VTE. The exposure of interest
      was treatment initiation with TNF-alpha inhibitor or nonbiologic (azathioprine,
      mercaptopurine, methotrexate, cyclosporine). The outcome of interest was
      admission to hospital with VTE as the principal diagnosis. We used Cox
      proportional hazard regression models to estimate hazard ratios (HRs) separately
      for each database after risk adjustment for more than 50 covariables using
      propensity score fine stratification. We used inverse variance meta-analytic
      methods to pool the adjusted HRs across the 3 databases. RESULTS: We included a
      total of 5173 patients who started TNF-alpha inhibitor therapy (1439 in the
      Medicaid database, 1480 in Medicare and 2254 in Optum Clinformatics) and 16 498
      who initiated a nonbiologic agent (5041 in Medicaid, 5166 in Medicare, 6291 in
      Optum Clinformatics). The adjusted pooled HR for VTE risk with TNF-alpha
      inhibitor versus a nonbiologic agent was 0.78 (95% confidence interval [CI] 0.60
      to 1.02). The HR was lower in patients with Crohn disease (pooled HR 0.62, 95% CI
      0.44 to 0.86) and younger patients (18-44 yr; pooled HR 0.55, 95% CI 0.34 to
      0.87). INTERPRETATION: We did not find a statistically significant association
      between risk of VTE and use of TNF-alpha inhibitors, relative to nonbiologics, in
      patients with IBD overall. However, an association was evident for patients
      younger than 45 years and those with Crohn disease.

PMID- 29180385
TI  - Treatment of venous thromboembolism in a 22-year-old woman taking an oral
      contraceptive pill.

PMID- 29180384
TI  - Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational
      postexposure prophylaxis.

PMID- 29180386
TI  - J-waves in hypothermia.

PMID- 29180387
TI  - Pigmented Bowen disease.

PMID- 29180388
TI  - Sexual orientation not included in analysis.

PMID- 29180389
TI  - Diagnostic coding of routinely collected data.

PMID- 29180390
TI  - Is it ever better not to have health insurance?

PMID- 29180391
TI  - Winds of growth may signal brewing health spending storm.

PMID- 29180392
TI  - Northwest Territories leads Canada in electronic medical record coverage.

PMID- 29180393
TI  - Segmental Sclerosis and Extracapillary Hypercellularity Predict Diabetic ESRD.
AB  - Pathogenetic markers of diabetic kidney disease (DKD) progression to ESRD are
      lacking. We characterized the prognostic value of histologic findings in DKD for
      time to ESRD in native kidney specimens from biopsies performed from 1995 to 2011
      with diabetic glomerulosclerosis as the only glomerular disease diagnosis
      (n=109). Biopsy specimens were analyzed according to standard methods, including
      determination of diabetic nephropathy class, as defined by the Renal Pathology
      Society. Clinical data were extracted from electronic medical records. We used
      competing risk models, with death as the competing risk, to estimate
      subdistribution hazard ratios (HRs) for ESRD. All multivariable models included
      age, sex, black race, baseline eGFR, and baseline proteinuria. Pathologic
      characteristics achieving P<0.1 were added into successively complex models. ESRD
      occurred in 56% of patients, and 26% of patients died before reaching ESRD. In
      univariate analyses, diabetic nephropathy class was not statistically significant
      in predicting time to ESRD. The final multivariable model (n=106) showed a
      borderline association between mild mesangial expansion and decreased risk for
      ESRD (subdistribution HR, 0.64; 95% confidence interval, 0.40 to 1.00). Poor
      prognostic factors in the final model included segmental sclerosis and
      extracapillary hypercellularity (subdistribution HR, 2.04; 95% confidence
      interval, 1.36 to 3.05; and subdistribution HR, 2.21; 95% confidence interval,
      1.19 to 4.11, respectively). In conclusion, we identified segmental sclerosis and
      extracapillary hypercellularity as novel, poor prognostic indicators of time from
      DKD to ESRD. Whether these indicators represent a distinct pathogenetic phenotype
      of DKD will require a large study with a broad spectrum of disease severity.

PMID- 29180394
TI  - Redirecting TGF-beta Signaling through the beta-Catenin/Foxo Complex Prevents
      Kidney Fibrosis.
AB  - TGF-beta is a key profibrotic factor, but targeting TGF-beta to prevent fibrosis
      also abolishes its protective anti-inflammatory effects. Here, we investigated
      the hypothesis that we can redirect TGF-beta signaling by preventing downstream
      profibrotic interaction of beta-catenin with T cell factor (TCF), thereby
      enhancing the interaction of beta-catenin with Foxo, a transcription factor that
      controls differentiation of TGF-beta induced regulatory T cells (iTregs), and
      thus, enhance anti-inflammatory effects of TGF-beta In iTregs derived from EL4 T
      cells treated with recombinant human TGF-beta1 (rhTGF-beta1) in vitro, inhibition
      of beta-catenin/TCF transcription with ICG-001 increased Foxp3 expression,
      interaction of beta-catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter,
      and Foxo transcriptional activity. Moreover, the level of beta-catenin expression
      positively correlated with the level of Foxo1 binding to the Foxp3 promoter and
      Foxo transcriptional activity. T cell fate mapping in Foxp3gfp Ly5.1/5.2 mice
      revealed that coadministration of rhTGF-beta1 and ICG-001 further enhanced the
      expansion of iTregs and natural Tregs observed with rhTGF-beta1 treatment alone.
      Coadministration of rhTGF-beta1 with ICG-001 also increased the number of Tregs
      and reduced inflammation and fibrosis in the kidney fibrosis models of unilateral
      ureteric obstruction and ischemia-reperfusion injury. Notably, ICG-001 prevented
      the fibrosis in distant organs (lung and liver) caused by rhTGF-beta1. Together,
      our results show that diversion of beta-catenin from TCF- to Foxo-mediated
      transcription inhibits the beta-catenin/TCF-mediated profibrotic effects of TGF
      beta while enhancing the beta-catenin/Foxo-mediated anti-inflammatory effects.
      Targeting beta-catenin/Foxo may be a novel therapeutic strategy in the treatment
      of fibrotic diseases that lead to organ failure.

PMID- 29180396
TI  - The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease.
AB  - The identification of genetic factors associated with kidney disease has the
      potential to provide critical insights into disease mechanisms. Genome-wide
      association studies have uncovered genomic regions associated with renal function
      metrics and risk of CKD. UMOD is among the most outstanding loci associated with
      CKD in the general population, because it has a large effect on eGFR and CKD risk
      that is consistent across different ethnic groups. The relevance of UMOD for CKD
      is clear, because the encoded protein, uromodulin (Tamm-Horsfall protein), is
      exclusively produced by the kidney tubule and has specific biochemical properties
      that mediate important functions in the kidney and urine. Rare mutations in UMOD
      are the major cause of autosomal dominant tubulointerstitial kidney disease, a
      condition that leads to CKD and ESRD. In this brief review, we use the UMOD
      paradigm to describe how population genetic studies can yield insight into the
      pathogenesis and prognosis of kidney diseases.

PMID- 29180395
TI  - Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney.
AB  - Tamm-Horsfall protein (THP), also known as uromodulin, is a kidney-specific
      protein produced by cells of the thick ascending limb of the loop of Henle.
      Although predominantly secreted apically into the urine, where it becomes highly
      polymerized, THP is also released basolaterally, toward the interstitium and
      circulation, to inhibit tubular inflammatory signaling. Whether, through this
      latter route, THP can also regulate the function of renal interstitial
      mononuclear phagocytes (MPCs) remains unclear, however. Here, we show that THP is
      primarily in a monomeric form in human serum. Compared with wild-type mice, THP-/
      mice had markedly fewer MPCs in the kidney. A nonpolymerizing, truncated form of
      THP stimulated the proliferation of human macrophage cells in culture and
      partially restored the number of kidney MPCs when administered to THP-/- mice.
      Furthermore, resident renal MPCs had impaired phagocytic activity in the absence
      of THP. After ischemia-reperfusion injury, THP-/- mice, compared with wild-type
      mice, exhibited aggravated injury and an impaired transition of renal macrophages
      toward an M2 healing phenotype. However, treatment of THP-/- mice with truncated
      THP after ischemia-reperfusion injury mitigated the worsening of AKI. Taken
      together, our data suggest that interstitial THP positively regulates mononuclear
      phagocyte number, plasticity, and phagocytic activity. In addition to the effect
      of THP on the epithelium and granulopoiesis, this new immunomodulatory role could
      explain the protection conferred by THP during AKI.

PMID- 29180397
TI  - ApoL1 Overexpression Drives Variant-Independent Cytotoxicity.
AB  - Coding variants in the APOL1 gene are associated with kidney diseases in African
      ancestral populations; yet, the underlying biologic mechanisms remain uncertain.
      Variant-dependent autophagic and cytotoxic cell death have been proposed as
      pathogenic pathways mediating kidney injury. To examine this possibility, we
      conditionally expressed APOL1-G0 (reference), -G1, and -G2 (variants) using a
      tetracycline-regulated system in HEK293 cells. Autophagy was monitored
      biochemically and cell death was measured using multiple assays. We measured
      intracellular Na+ and K+ content with atomic absorption spectroscopy and APOL1
      dependent currents with whole-cell patch clamping. Neither reference nor variant
      APOL1s induced autophagy. At high expression levels, APOL1-G0, -G1, and -G2
      inserted into the plasma membrane and formed pH-sensitive cation channels,
      causing collapse of cellular Na+ and K+ gradients, phosphorylation of p38 mitogen
      activated protein kinase, and cell death, without variant-dependent differences.
      APOL1-G0 and -G2 exhibited similar channel properties in whole-cell patch clamp
      experiments. At low expression levels, neither reference nor variant APOL1s
      localized on the plasma membrane, Na+ and K+ gradients were maintained, and cells
      remained viable. Our results indicate that APOL1-mediated pore formation is
      critical for the trypanolytic activity of APOL1 and drives APOL1-mediated
      cytotoxicity in overexpression systems. The absence of cytotoxicity at
      physiologic expression levels suggests variant-dependent intracellular K+ loss
      and cytotoxicity does not drive kidney disease progression.

PMID- 29180398
TI  - Inhibition of heme oxygenase ameliorates anemia and reduces iron overload in a
      beta-thalassemia mouse model.
AB  - Thalassemias are a heterogeneous group of red blood cell disorders, considered a
      major cause of morbidity and mortality among genetic diseases. However, there is
      still no universally available cure for thalassemias. The underlying basis of
      thalassemia pathology is the premature apoptotic destruction of erythroblasts
      causing ineffective erythropoiesis. In beta-thalassemia, beta-globin synthesis is
      reduced causing alpha-globin accumulation. Unpaired globin chains, with heme
      attached to them, accumulate in thalassemic erythroblasts causing oxidative
      stress and the premature cell death. We hypothesize that in beta-thalassemia heme
      oxygenase (HO) 1 could play a pathogenic role in the development of anemia and
      ineffective erythropoiesis. To test this hypothesis, we exploited a mouse model
      of beta-thalassemia intermedia, Th3/+ We observed that HO inhibition using tin
      protoporphyrin IX (SnPP) decreased heme-iron recycling in the liver and
      ameliorated anemia in the Th3/+ mice. SnPP administration led to a decrease in
      erythropoietin and increase in hepcidin serum levels, changes that were
      accompanied by an alleviation of ineffective erythropoiesis in Th3/+ mice.
      Additionally, the bone marrow from Th3/+ mice treated with SnPP exhibited
      decreased heme catabolism and diminished iron release as well as reduced
      apoptosis. Our results indicate that the iron released from heme because of HO
      activity contributes to the pathophysiology of thalassemia. Therefore, new
      therapies that suppress heme catabolism may be beneficial in ameliorating the
      anemia and ineffective erythropoiesis in thalassemias.

PMID- 29180400
TI  - First report of ibrutinib in IgM-related amyloidosis: few responses, poor
      tolerability, and short survival.

PMID- 29180401
TI  - Predicting phenological shifts in a changing climate.
AB  - Phenological shifts constitute one of the clearest manifestations of climate
      warming. Advanced emergence is widely reported in high-latitude ectotherms, but a
      significant number of species exhibit delayed, or no change in, emergence. Here
      we present a mechanistic theoretical framework that reconciles these disparate
      observations and predicts population-level phenological patterns based solely on
      data on temperature responses of the underlying life history traits. Our model,
      parameterized with data from insects at different latitudes, shows that peak
      abundance occurs earlier in the year when warming increases the mean
      environmental temperature, but is delayed when warming increases the amplitude of
      seasonal fluctuations. We find that warming does not necessarily lead to a longer
      activity period in high-latitude species because it elevates summer temperatures
      above the upper limit for reproduction and development. Our findings both confirm
      and confound expectations for ectotherm species affected by climate warming: an
      increase in the mean temperature is more detrimental to low-latitude species
      adapted to high mean temperatures and low-amplitude seasonal fluctuations; an
      increase in seasonal fluctuations is more detrimental to high-latitude species
      adapted to low mean temperatures and high-amplitude fluctuations.

PMID- 29180399
TI  - Diminished microRNA-29b level is associated with BRD4-mediated activation of
      oncogenes in cutaneous T-cell lymphoma.
AB  - MicroRNA (miRNA) dysregulation is a hallmark of cutaneous T-cell lymphoma (CTCL),
      an often-fatal malignancy of skin-homing CD4+ T cells for which there are few
      effective therapies. The role of microRNAs (miRs) in controlling epigenetic
      modifier-dependent transcriptional regulation in CTCL is unknown. In this study,
      we characterize a novel miR dysregulation that contributes to overexpression of
      the epigenetic reader bromodomain-containing protein 4 (BRD4). We used patient
      CD4+ T cells to show diminished levels of miR-29b compared with healthy donor
      cells. Patient cells and miR-29b-/- mouse cells revealed an inverse relationship
      between miR-29b and BRD4, the latter of which is overexpressed in these cells.
      Chromatin immunoprecipitation and sequencing analysis revealed increased genome
      wide BRD4 occupancy at promoter and enhancer regions in CD4+ T cells from CTCL
      patients. The cumulative result of BRD4 binding was increased expression of tumor
      associated genes such as NOTCH1 and RBPJ, as well as the interleukin-15 (IL-15)
      receptor complex, the latter enhancing IL-15 autocrine signaling. Furthermore, we
      confirm the in vivo relevance of this pathway in our IL-15 transgenic mouse model
      of CTCL by showing that interference with BRD4-mediated pathogenesis, either by
      restoring miR-29b levels via bortezomib treatment or by directly inhibiting BRD4
      binding via JQ1 treatment, prevents progression of CTCL. We describe a novel
      oncogenic pathway featuring IL-15, miR-29b, and BRD4 in CTCL and suggest
      targeting of these components as a potentially effective therapy for CTCL
      patients.

PMID- 29180402
TI  - Fishnet model for failure probability tail of nacre-like imbricated lamellar
      materials.
AB  - Nacre, the iridescent material of the shells of pearl oysters and abalone,
      consists mostly of aragonite (a form of CaCO3), a brittle constituent of
      relatively low strength ([Formula: see text]10 MPa). Yet it has astonishing mean
      tensile strength ([Formula: see text]150 MPa) and fracture energy ([Formula: see
      text]350 to 1,240 J/m2). The reasons have recently become well understood: (i)
      the nanoscale thickness ([Formula: see text]300 nm) of nacre's building blocks,
      the aragonite lamellae (or platelets), and (ii) the imbricated, or staggered,
      arrangement of these lamellea, bound by biopolymer layers only [Formula: see
      text]25 nm thick, occupying [Formula: see text] of volume. These properties
      inspire manmade biomimetic materials. For engineering applications, however, the
      failure probability of [Formula: see text] is generally required. To guarantee
      it, the type of probability density function (pdf) of strength, including its
      tail, must be determined. This objective, not pursued previously, is hardly
      achievable by experiments alone, since [Formula: see text] tests of specimens
      would be needed. Here we outline a statistical model of strength that resembles a
      fishnet pulled diagonally, captures the tail of pdf of strength and, importantly,
      allows analytical safety assessments of nacreous materials. The analysis shows
      that, in terms of safety, the imbricated lamellar structure provides a major
      additional advantage-~10% strength increase at tail failure probability [Formula:
      see text] and a 1 to 2 orders of magnitude tail probability decrease at fixed
      stress. Another advantage is that a high scatter of microstructure properties
      diminishes the strength difference between the mean and the probability tail,
      compared with the weakest link model. These advantages of nacre-like materials
      are here justified analytically and supported by millions of Monte Carlo
      simulations.

PMID- 29180404
TI  - Correction for Schulte et al., Prairie strips improve biodiversity and the
      delivery of multiple ecosystem services from corn-soybean croplands.

PMID- 29180403
TI  - SUMOylation and ubiquitination reciprocally regulate alpha-synuclein degradation
      and pathological aggregation.
AB  - alpha-Synuclein accumulation is a pathological hallmark of Parkinson's disease
      (PD). Ubiquitinated alpha-synuclein is targeted to proteasomal or lysosomal
      degradation. Here, we identify SUMOylation as a major mechanism that counteracts
      ubiquitination by different E3 ubiquitin ligases and regulates alpha-synuclein
      degradation. We report that PIAS2 promotes SUMOylation of alpha-synuclein,
      leading to a decrease in alpha-synuclein ubiquitination by SIAH and Nedd4
      ubiquitin ligases, and causing its accumulation and aggregation into inclusions.
      This was associated with an increase in alpha-synuclein release from the cells. A
      SUMO E1 inhibitor, ginkgolic acid, decreases alpha-synuclein levels by relieving
      the inhibition exerted on alpha-synuclein proteasomal degradation. alpha
      Synuclein disease mutants are more SUMOylated compared with the wild-type
      protein, and this is associated with increased aggregation and inclusion
      formation. We detected a marked increase in PIAS2 expression along with
      SUMOylated alpha-synuclein in PD brains, providing a causal mechanism underlying
      the up-regulation of alpha-synuclein SUMOylation in the disease. We also found a
      significant proportion of Lewy bodies in nigral neurons containing SUMO1 and
      PIAS2. Our observations suggest that SUMOylation of alpha-synuclein by PIAS2
      promotes alpha-synuclein aggregation by two mutually reinforcing mechanisms.
      First, it has a direct proaggregatory effect on alpha-synuclein. Second,
      SUMOylation facilitates alpha-synuclein aggregation by blocking its ubiquitin
      dependent degradation pathways and promoting its accumulation. Therefore,
      inhibitors of alpha-synuclein SUMOylation provide a strategy to reduce alpha
      synuclein levels and possibly aggregation in PD.

PMID- 29180405
TI  - Hydraulic fracturing near domestic groundwater wells.
AB  - Hydraulic fracturing operations are generating considerable discussion about
      their potential to contaminate aquifers tapped by domestic groundwater wells.
      Groundwater wells located closer to hydraulically fractured wells are more likely
      to be exposed to contaminants derived from on-site spills and well-bore failures,
      should they occur. Nevertheless, the proximity of hydraulic fracturing operations
      to domestic groundwater wells is unknown. Here, we analyze the distance between
      domestic groundwater wells (public and self-supply) constructed between 2000 and
      2014 and hydraulically fractured wells stimulated in 2014 in 14 states. We show
      that 37% of all recorded hydraulically fractured wells stimulated during 2014
      exist within 2 km of at least one recently constructed (2000-2014) domestic
      groundwater well. Furthermore, we identify 11 counties where most ([Formula: see
      text]50%) recorded domestic groundwater wells exist within 2 km of one or more
      hydraulically fractured wells stimulated during 2014. Our findings suggest that
      understanding how frequently hydraulic fracturing operations impact groundwater
      quality is of widespread importance to drinking water safety in many areas where
      hydraulic fracturing is common. We also identify 236 counties where most recorded
      domestic groundwater wells exist within 2 km of one or more recorded oil and gas
      wells producing during 2014. Our analysis identifies hotspots where both
      conventional and unconventional oil and gas wells frequently exist near recorded
      domestic groundwater wells that may be targeted for further water-quality
      monitoring.

PMID- 29180406
TI  - Coupled European and Greenland last glacial dust activity driven by North
      Atlantic climate.
AB  - Centennial-scale mineral dust peaks in last glacial Greenland ice cores match the
      timing of lowest Greenland temperatures, yet little is known of equivalent
      changes in dust-emitting regions, limiting our understanding of dust-climate
      interaction. Here, we present the most detailed and precise age model for
      European loess dust deposits to date, based on 125 accelerator mass spectrometry
      14C ages from Dunaszekcso, Hungary. The record shows that variations in glacial
      dust deposition variability on centennial-millennial timescales in east central
      Europe and Greenland were synchronous within uncertainty. We suggest that
      precipitation and atmospheric circulation changes were likely the major
      influences on European glacial dust activity and propose that European dust
      emissions were modulated by dominant phases of the North Atlantic Oscillation,
      which had a major influence on vegetation and local climate of European dust
      source regions.

PMID- 29180407
TI  - Glycosyltransferase MDR1 assembles a dividing ring for mitochondrial
      proliferation comprising polyglucan nanofilaments.
AB  - Mitochondria, which evolved from a free-living bacterial ancestor, contain their
      own genomes and genetic systems and are produced from preexisting mitochondria by
      binary division. The mitochondrion-dividing (MD) ring is the main skeletal
      structure of the mitochondrial division machinery. However, the assembly
      mechanism and molecular identity of the MD ring are unknown. Multi-omics analysis
      of isolated mitochondrial division machinery from the unicellular alga
      Cyanidioschyzon merolae revealed an uncharacterized glycosyltransferase,
      MITOCHONDRION-DIVIDING RING1 (MDR1), which is specifically expressed during
      mitochondrial division and forms a single ring at the mitochondrial division
      site. Nanoscale imaging using immunoelectron microscopy and componential analysis
      demonstrated that MDR1 is involved in MD ring formation and that the MD ring
      filaments are composed of glycosylated MDR1 and polymeric glucose nanofilaments.
      Down-regulation of MDR1 strongly interrupted mitochondrial division and
      obstructed MD ring assembly. Taken together, our results suggest that MDR1
      mediates the synthesis of polyglucan nanofilaments that assemble to form the MD
      ring. Given that a homolog of MDR1 performs similar functions in chloroplast
      division, the establishment of MDR1 family proteins appears to have been a
      singular, crucial event for the emergence of endosymbiotic organelles.

PMID- 29180409
TI  - Correction to Supporting Information for Alvarez et al., Human genetic variation
      in VAC14 regulates Salmonella invasion and typhoid fever through modulation of
      cholesterol.

PMID- 29180408
TI  - In situ modeling of multimodal floral cues attracting wild pollinators across
      environments.
AB  - With more than 80% of flowering plant species specialized for animal pollination,
      understanding how wild pollinators utilize resources across environments can
      encourage efficient planting and maintenance strategies to maximize pollination
      and establish resilience in the face of environmental change. A fundamental
      question is how generalist pollinators recognize "flower objects" in vastly
      different ecologies and environments. On one hand, pollinators could employ a
      specific set of floral cues regardless of environment. Alternatively, wild
      pollinators could recognize an exclusive signature of cues unique to each
      environment or flower species. Hoverflies, which are found across the globe, are
      one of the most ecologically important alternative pollinators after bees and
      bumblebees. Here, we have exploited their cosmopolitan status to understand how
      wild pollinator preferences change across different continents. Without employing
      any a priori assumptions concerning the floral cues, we measured, predicted, and
      finally artificially recreated multimodal cues from individual flowers visited by
      hoverflies in three different environments (hemiboreal, alpine, and tropical)
      using a field-based methodology. We found that although "flower signatures" were
      unique for each environment, some multimodal lures were ubiquitously attractive,
      despite not carrying any reward, or resembling real flowers. While it was
      unexpected that cue combinations found in real flowers were not necessary, the
      robustness of our lures across insect species and ecologies could reflect a
      general strategy of resource identification for generalist pollinators. Our
      results provide insights into how cosmopolitan pollinators such as hoverflies
      identify flowers and offer specific ecologically based cues and strategies for
      attracting pollinators across diverse environments.

PMID- 29180411
TI  - Correction for Alvarez et al., Human genetic variation in VAC14 regulates
      Salmonella invasion and typhoid fever through modulation of cholesterol.

PMID- 29180410
TI  - Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk,
      regulating cortical neurogenesis.
AB  - The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell
      fate determination during corticogenesis. During neuronal differentiation, the
      Ryk intracellular domain (ICD) is cleaved. Cleavage of Ryk and nuclear
      translocation of Ryk-ICD are required for neuronal differentiation. However, the
      mechanism of translocation and how it regulates neuronal differentiation remain
      unclear. Here, we identified Smek1 and Smek2 as Ryk-ICD partners that regulate
      its nuclear localization and function together with Ryk-ICD in the nucleus
      through chromatin recruitment and gene transcription regulation. Smek1/2 double
      knockout mice displayed pronounced defects in the production of cortical neurons,
      especially interneurons, while the neural stem cell population increased. In
      addition, both Smek and Ryk-ICD bound to the Dlx1/2 intergenic regulator element
      and were involved in its transcriptional regulation. These findings demonstrate a
      mechanism of the Ryk signaling pathway in which Smek1/2 and Ryk-ICD work together
      to mediate neural cell fate during corticogenesis.

PMID- 29180413
TI  - Correction for Kang et al., Increased intracellular Ca2+ concentrations prevent
      membrane localization of PH domains through the formation of Ca2+
      phosphoinositides.

PMID- 29180412
TI  - Membrane targeting of inhibitory Smads through palmitoylation controls TGF
      beta/BMP signaling.
AB  - TGF-beta/BMP (bone morphogenetic protein) signaling pathways play conserved roles
      in controlling embryonic development, tissue homeostasis, and stem cell
      regulation. Inhibitory Smads (I-Smads) have been shown to negatively regulate TGF
      beta/BMP signaling by primarily targeting the type I receptors for ubiquitination
      and turnover. However, little is known about how I-Smads access the membrane to
      execute their functions. Here we show that Dad, the Drosophila I-Smad, associates
      with the cellular membrane via palmitoylation, thereby targeting the BMP type I
      receptor for ubiquitination. By performing systematic biochemistry assays, we
      characterized the specific cysteine (Cys556) essential for Dad palmitoylation and
      membrane association. Moreover, we demonstrate that dHIP14, a Drosophila
      palmitoyl acyl-transferase, catalyzes Dad palmitoylation, thereby inhibiting
      efficient BMP signaling. Thus, our findings uncover a modification of the
      inhibitory Smads that controls TGF-beta/BMP signaling activity.

PMID- 29180414
TI  - Correction to Supporting Information for Sculley et al., Eighty years of food-web
      response to interannual variation in discharge recorded in river diatom frustules
      from an ocean sediment core.

PMID- 29180416
TI  - Fluid-driven origami-inspired artificial muscles.
AB  - Artificial muscles hold promise for safe and powerful actuation for myriad common
      machines and robots. However, the design, fabrication, and implementation of
      artificial muscles are often limited by their material costs, operating
      principle, scalability, and single-degree-of-freedom contractile actuation
      motions. Here we propose an architecture for fluid-driven origami-inspired
      artificial muscles. This concept requires only a compressible skeleton, a
      flexible skin, and a fluid medium. A mechanical model is developed to explain the
      interaction of the three components. A fabrication method is introduced to
      rapidly manufacture low-cost artificial muscles using various materials and at
      multiple scales. The artificial muscles can be programed to achieve multiaxial
      motions including contraction, bending, and torsion. These motions can be
      aggregated into systems with multiple degrees of freedom, which are able to
      produce controllable motions at different rates. Our artificial muscles can be
      driven by fluids at negative pressures (relative to ambient). This feature makes
      actuation safer than most other fluidic artificial muscles that operate with
      positive pressures. Experiments reveal that these muscles can contract over 90%
      of their initial lengths, generate stresses of ~600 kPa, and produce peak power
      densities over 2 kW/kg-all equal to, or in excess of, natural muscle. This
      architecture for artificial muscles opens the door to rapid design and low-cost
      fabrication of actuation systems for numerous applications at multiple scales,
      ranging from miniature medical devices to wearable robotic exoskeletons to large
      deployable structures for space exploration.

PMID- 29180415
TI  - WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback
      loop in Mycobacterium marinum.
AB  - ESX (ESAT-6 system) export systems play diverse roles across mycobacterial
      species. Interestingly, genetic disruption of ESX systems in different species
      does not result in an accumulation of protein substrates in the mycobacterial
      cell. However, the mechanisms underlying this observation are elusive. We
      hypothesized that the levels of ESX substrates were regulated by a feedback
      control mechanism, linking the levels of substrates to the secretory status of
      ESX systems. To test this hypothesis, we used a combination of genetic,
      transcriptomic, and proteomic approaches to define export-dependent mechanisms
      regulating the levels of ESX-1 substrates in Mycobacterium marinum WhiB6 is a
      transcription factor that regulates expression of genes encoding ESX-1
      substrates. We found that, in the absence of the genes encoding conserved
      membrane components of the ESX-1 system, the expression of the whiB6 gene and
      genes encoding ESX-1 substrates were reduced. Accordingly, the levels of ESX-1
      substrates were decreased, and WhiB6 was not detected in M. marinum strains
      lacking genes encoding ESX-1 components. We demonstrated that, in the absence of
      EccCb1, a conserved ESX-1 component, substrate gene expression was restored by
      constitutive, but not native, expression of the whiB6 gene. Finally, we found
      that the loss of WhiB6 resulted in a virulent M. marinum strain with reduced ESX
      1 secretion. Together, our findings demonstrate that the levels of ESX-1
      substrates in M. marinum are fine-tuned by negative feedback control, linking the
      expression of the whiB6 gene to the presence, not the functionality, of the ESX-1
      membrane complex.

PMID- 29180418
TI  - Correction for Schroeder et al., Mutagenic cost of ribonucleotides in bacterial
      DNA.

PMID- 29180417
TI  - SNX8 mediates IFNgamma-triggered noncanonical signaling pathway and host defense
      against Listeria monocytogenes.
AB  - IFNgamma is a cytokine that plays a key role in host defense against
      intracellular pathogens. In addition to the canonical JAK-STAT1 pathway, IFNgamma
      also activates an IKKbeta-mediated noncanonical signaling pathway that is
      essential for induction of a subset of downstream effector genes. The molecular
      mechanisms and functional significance of this IFNgamma-triggered noncanonical
      pathway remains enigmatic. Here, we identified sorting nexin 8 (SNX8) as an
      important component of the IFNgamma-triggered noncanonical signaling pathway.
      SNX8-deficiency impaired IFNgamma-triggered induction of a subset of downstream
      genes. Snx8-/- mice infected with Listeria monocytogenes exhibited lower serum
      cytokine levels and higher bacterial loads in the livers and spleens, resulting
      in higher lethality. Mechanistically, SNX8 interacted with JAK1 and IKKbeta and
      promoted their association. IFNgamma induced JAK1-mediated phosphorylation of
      SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKbeta to the JAK1
      complex. SNX8-deficiency impaired IFNgamma-induced oligomerization and
      autophosphorylation of IKKbeta at Ser177, which is critical for selective
      induction of downstream genes. Our findings suggest that SNX8 acts as a link for
      IFNgamma-triggered noncanonical signaling pathway, which induces a subset of
      downstream genes important for host defense against L. monocytogenes infection.

PMID- 29180419
TI  - Chiral intertwined spirals and magnetic transition dipole moments dictated by
      cylinder helicity.
AB  - The presence of anomalous chirality in a roll of graphitic carbon sheets has been
      recognized since the discovery of carbon nanotubes, which are becoming available
      in higher quantities through the isolation of chiral single-wall congeners with
      high purity. Exploration of the properties arising from cylinder chirality is
      expected to expand the scope of tubular entities in the future. By studying
      molecular fragments of helical carbon nanotubes, we herein reveal interesting
      properties that arise from this chirality. The chirality of nanoscale cylinders
      resulted in chirality of larger dimensions in the form of a double-helix
      assembly. Cylinder chirality in solution gave rise to a large dissymmetry factor
      of metal-free entities in circular polarized luminescence. Theoretical
      investigations revealed the pivotal role of cylindrical shapes in enhancing
      magnetic dipole transition moments to yield extreme rotatory strength. Unique
      effects of cylinder chirality in this study may prompt the development of tubular
      entities, for instance, toward chiroptical applications.

PMID- 29180420
TI  - Structures and enzymatic mechanisms of phycobiliprotein lyases CpcE/F and PecE/F.
AB  - The light-harvesting phycobilisome in cyanobacteria and red algae requires the
      lyase-catalyzed chromophorylation of phycobiliproteins. There are three
      functionally distinct lyase families known. The heterodimeric E/F type is
      specific for attaching bilins covalently to alpha-subunits of phycocyanins and
      phycoerythrins. Unlike other lyases, the lyase also has chromophore-detaching
      activity. A subclass of the E/F-type lyases is, furthermore, capable of
      chemically modifying the chromophore. Although these enzymes were characterized
      >25 y ago, their structures remained unknown. We determined the crystal structure
      of the heterodimer of CpcE/F from Nostoc sp. PCC7120 at 1.89-A resolution. Both
      subunits are twisted, crescent-shaped alpha-solenoid structures. CpcE has 15 and
      CpcF 10 helices. The inner (concave) layer of CpcE (helices h2, 4, 6, 8, 10, 12,
      and 14) and the outer (convex) layer of CpcF (h16, 18, 20, 22, and 24) form a
      cavity into which the phycocyanobilin chromophore can be modeled. This location
      of the chromophore is supported by mutations at the interface between the
      subunits and within the cavity. The structure of a structurally related,
      isomerizing lyase, PecE/F, that converts phycocyanobilin into phycoviolobilin,
      was modeled using the CpcE/F structure as template. A H87C88 motif critical for
      the isomerase activity of PecE/F is located at the loop between h20 and h21,
      supporting the proposal that the nucleophilic addition of Cys-88 to C10 of
      phycocyanobilin induces the isomerization of phycocyanobilin into
      phycoviolobilin. Also, the structure of NblB, involved in phycobilisome
      degradation could be modeled using CpcE as template. Combined with CpcF, NblB
      shows a low chromophore-detaching activity.

PMID- 29180422
TI  - Storm, rogue wave, or tsunami origin for megaclast deposits in western Ireland
      and North Island, New Zealand?
AB  - The origins of boulderite deposits are investigated with reference to the present
      day foreshore of Annagh Head, NW Ireland, and the Lower Miocene Matheson
      Formation, New Zealand, to resolve disputes on their origin and to contrast and
      compare the deposits of tsunamis and storms. Field data indicate that the
      Matheson Formation, which contains boulders in excess of 140 tonnes, was produced
      by a 12- to 13-m-high tsunami with a period in the order of 1 h. The origin of
      the boulders at Annagh Head, which exceed 50 tonnes, is disputed. We combine
      oceanographic, historical, and field data to argue that this is a cliff-top storm
      deposit (CTSD). A numerical model for CTSDs is developed which indicates that
      boulder shape in addition to density and dimensions should be taken into account
      when applying hydrodynamic equations to such deposits. The model also predicts
      that the NE Atlantic storms are capable of producing boulderites that, when size
      alone is considered, cannot be distinguished from tsunamites. We review the
      characteristics that identify the origins of these two deposits.

PMID- 29180421
TI  - Metal transporter Slc39a10 regulates susceptibility to inflammatory stimuli by
      controlling macrophage survival.
AB  - Zn plays a key role in controlling macrophage function during an inflammatory
      event. Cellular Zn homeostasis is regulated by two families of metal
      transporters, the SLC39A family of importers and the SLC30A family of exporters;
      however, the precise role of these transporters in maintaining macrophage
      function is poorly understood. Using macrophage-specific Slc39a10-knockout
      (Slc39a10fl/fl;LysM-Cre+ ) mice, we found that Slc39a10 plays an essential role
      in macrophage survival by mediating Zn homeostasis in response to LPS
      stimulation. Compared with Slc39a10fl/fl mice, Slc39a10fl/fl;LysM-Cre+ mice had
      significantly lower mortality following LPS stimulation as well as reduced liver
      damage and lower levels of circulating inflammatory cytokines. Moreover, reduced
      intracellular Zn concentration in Slc39a10fl/fl;LysM-Cre+ macrophages led to the
      stabilization of p53, which increased apoptosis upon LPS stimulation. Concomitant
      knockout of p53 largely rescued the phenotype of Slc39a10fl/fl;LysM-Cre+ mice.
      Finally, the phenotype in Slc39a10fl/fl;LysM-Cre+ mice was mimicked in wild-type
      mice using the Zn chelator TPEN and was reversed with Zn supplementation. Taken
      together, these results suggest that Slc39a10 plays a role in promoting the
      survival of macrophages through a Zn/p53-dependent axis in response to
      inflammatory stimuli.

PMID- 29180424
TI  - Causes of ice age intensification across the Mid-Pleistocene Transition.
AB  - During the Mid-Pleistocene Transition (MPT; 1,200-800 kya), Earth's orbitally
      paced ice age cycles intensified, lengthened from ~40,000 (~40 ky) to ~100 ky,
      and became distinctly asymmetrical. Testing hypotheses that implicate changing
      atmospheric CO2 levels as a driver of the MPT has proven difficult with available
      observations. Here, we use orbitally resolved, boron isotope CO2 data to show
      that the glacial to interglacial CO2 difference increased from ~43 to ~75 MUatm
      across the MPT, mainly because of lower glacial CO2 levels. Through carbon cycle
      modeling, we attribute this decline primarily to the initiation of substantive
      dust-borne iron fertilization of the Southern Ocean during peak glacial stages.
      We also observe a twofold steepening of the relationship between sea level and
      CO2-related climate forcing that is suggestive of a change in the dynamics that
      govern ice sheet stability, such as that expected from the removal of subglacial
      regolith or interhemispheric ice sheet phase-locking. We argue that neither ice
      sheet dynamics nor CO2 change in isolation can explain the MPT. Instead, we infer
      that the MPT was initiated by a change in ice sheet dynamics and that longer and
      deeper post-MPT ice ages were sustained by carbon cycle feedbacks related to dust
      fertilization of the Southern Ocean as a consequence of larger ice sheets.

PMID- 29180423
TI  - Prenatal stress accelerates offspring growth to compensate for reduced maternal
      investment across mammals.
AB  - Across mammals, prenatal maternal stress (PREMS) affects many aspects of
      offspring development, including offspring growth. However, how PREMS translates
      to offspring growth is inconsistent, even within species. To explain the full
      range of reported effects of prenatal adversity on offspring growth, we propose
      an integrative hypothesis: developmental constraints and a counteracting adaptive
      growth plasticity work in opposition to drive PREMS effects on growth. Mothers
      experiencing adversity reduce maternal investment leading to stunted growth
      (developmental constraints). Concomitantly, the pace of offspring life history is
      recalibrated to partly compensate for these developmental constraints (adaptive
      growth plasticity). Moreover, the relative importance of each process changes
      across ontogeny with increasing offspring independence. Thus, offspring exposed
      to PREMS may grow at the same rate as controls during gestation and lactation,
      but faster after weaning when direct maternal investment has ceased. We tested
      these predictions with a comparative analysis on the outcomes of 719 studies
      across 21 mammal species. First, the observed growth changes in response to PREMS
      varied across offspring developmental periods as predicted. We argue that the
      observed growth acceleration after weaning is not "catch-up growth," because
      offspring that were small for age grew slower. Second, only PREMS exposure early
      during gestation produced adaptive growth plasticity. Our results suggest that
      PREMS effects benefit the mother's future reproduction and at the same time
      accelerate offspring growth and possibly maturation and reproductive rate. In
      this sense, PREMS effects on offspring growth allow mother and offspring to make
      the best of a bad start.

PMID- 29180425
TI  - Interaction of intramembrane metalloprotease SpoIVFB with substrate Pro-sigmaK.
AB  - Intramembrane proteases (IPs) cleave membrane-associated substrates in nearly all
      organisms and regulate diverse processes. A better understanding of how these
      enzymes interact with their substrates is necessary for rational design of IP
      modulators. We show that interaction of Bacillus subtilis IP SpoIVFB with its
      substrate Pro-sigmaK depends on particular residues in the interdomain linker of
      SpoIVFB. The linker plus either the N-terminal membrane domain or the C-terminal
      cystathione-beta-synthase (CBS) domain of SpoIVFB was sufficient for the
      interaction but not for cleavage of Pro-sigmaK Chemical cross-linking and mass
      spectrometry of purified, inactive SpoIVFB-Pro-sigmaK complex indicated residues
      of the two proteins in proximity. A structural model of the complex was built via
      partial homology and by using constraints based on cross-linking data. In the
      model, the Proregion of Pro-sigmaK loops into the membrane domain of SpoIVFB, and
      the rest of Pro-sigmaK interacts extensively with the linker and the CBS domain
      of SpoIVFB. The extensive interaction is proposed to allow coordination between
      ATP binding by the CBS domain and Pro-sigmaK cleavage by the membrane domain.

PMID- 29180426
TI  - Proton movement and coupling in the POT family of peptide transporters.
AB  - POT transporters represent an evolutionarily well-conserved family of proton
      coupled transport systems in biology. An unusual feature of the family is their
      ability to couple the transport of chemically diverse ligands to an inwardly
      directed proton electrochemical gradient. For example, in mammals, fungi, and
      bacteria they are predominantly peptide transporters, whereas in plants the
      family has diverged to recognize nitrate, plant defense compounds, and hormones.
      Although recent structural and biochemical studies have identified conserved
      sites of proton binding, the mechanism through which transport is coupled to
      proton movement remains enigmatic. Here we show that different POT transporters
      operate through distinct proton-coupled mechanisms through changes in the
      extracellular gate. A high-resolution crystal structure reveals the presence of
      ordered water molecules within the peptide binding site. Multiscale molecular
      dynamics simulations confirm proton transport occurs through these waters via
      Grotthuss shuttling and reveal that proton binding to the extracellular side of
      the transporter facilitates a reorientation from an inward- to outward-facing
      state. Together these results demonstrate that within the POT family multiple
      mechanisms of proton coupling have likely evolved in conjunction with variation
      of the extracellular gate.

PMID- 29180428
TI  - Development of self-protective biases in response to social evaluative feedback.
AB  - Adolescence is a developmental period marked by heightened attunement to social
      evaluation. While adults have been shown to enact self-protective processes to
      buffer their self-views from evaluative threats like peer rejection, it is
      unclear whether adolescents avail themselves of the same defenses. The present
      study examines how social evaluation shapes views of the self and others
      differently across development. N = 107 participants ages 10-23 completed a
      reciprocal social evaluation task that involved predicting and receiving peer
      acceptance and rejection feedback, along with assessments of self-views and
      likability ratings of peers. Here, we show that, despite equivalent experiences
      of social evaluation, adolescents internalized peer rejection, experiencing a
      feedback-induced drop in self-views, whereas adults externalized peer rejection,
      reporting a task-induced boost in self-views and deprecating the peers who
      rejected them. The results identify codeveloping processes underlying why peer
      rejection may lead to more dramatic alterations in self-views during adolescence
      than other phases of the lifespan.

PMID- 29180427
TI  - AP-4 mediates export of ATG9A from the trans-Golgi network to promote
      autophagosome formation.
AB  - AP-4 is a member of the heterotetrameric adaptor protein (AP) complex family
      involved in protein sorting in the endomembrane system of eukaryotic cells.
      Interest in AP-4 has recently risen with the discovery that mutations in any of
      its four subunits cause a form of hereditary spastic paraplegia (HSP) with
      intellectual disability. The critical sorting events mediated by AP-4 and the
      pathogenesis of AP-4 deficiency, however, remain poorly understood. Here we
      report the identification of ATG9A, the only multispanning membrane component of
      the core autophagy machinery, as a specific AP-4 cargo. AP-4 promotes signal
      mediated export of ATG9A from the trans-Golgi network to the peripheral
      cytoplasm, contributing to lipidation of the autophagy protein LC3B and
      maturation of preautophagosomal structures. These findings implicate AP-4 as a
      regulator of autophagy and altered autophagy as a possible defect in AP-4
      deficient HSP.

PMID- 29180429
TI  - Kinematics of flagellar swimming in Euglena gracilis: Helical trajectories and
      flagellar shapes.
AB  - The flagellar swimming of euglenids, which are propelled by a single anterior
      flagellum, is characterized by a generalized helical motion. The 3D nature of
      this swimming motion, which lacks some of the symmetries enjoyed by more common
      model systems, and the complex flagellar beating shapes that power it make its
      quantitative description challenging. In this work, we provide a quantitative,
      3D, highly resolved reconstruction of the swimming trajectories and flagellar
      shapes of specimens of Euglena gracilis We achieved this task by using high-speed
      2D image recordings taken with a conventional inverted microscope combined with a
      precise characterization of the helical motion of the cell body to lift the 2D
      data to 3D trajectories. The propulsion mechanism is discussed. Our results
      constitute a basis for future biophysical research on a relatively unexplored
      type of eukaryotic flagellar movement.

PMID- 29180430
TI  - Def1 interacts with TFIIH and modulates RNA polymerase II transcription.
AB  - The DNA damage response is an essential process for the survival of living cells.
      In a subset of stress-responsive genes in humans, Elongin controls transcription
      in response to multiple stimuli, such as DNA damage, oxidative stress, and heat
      shock. Yeast Elongin (Ela1-Elc1), along with Def1, is known to facilitate
      ubiquitylation and degradation of RNA polymerase II (pol II) in response to
      multiple stimuli, yet transcription activity has not been examined. We have found
      that Def1 copurifies from yeast whole-cell extract with TFIIH, the largest
      general transcription factor required for transcription initiation and nucleotide
      excision repair. The addition of recombinant Def1 and Ela1-Elc1 enhanced
      transcription initiation in an in vitro reconstituted system including pol II,
      the general transcription factors, and TFIIS. Def1 also enhanced transcription
      restart from TFIIS-induced cleavage in a pol II transcribing complex. In the
      Deltadef1 strain, heat shock genes were misregulated, indicating that Def1 is
      required for induction of some stress-responsive genes in yeast. Taken together,
      our results extend the understanding of the molecular mechanism of transcription
      regulation on cellular stress and reveal functional similarities to the mammalian
      system.

PMID- 29180431
TI  - Amorphous MoS3 as the sulfur-equivalent cathode material for room-temperature Li
      S and Na-S batteries.
AB  - Many problems associated with Li-S and Na-S batteries essentially root in the
      generation of their soluble polysulfide intermediates. While conventional wisdom
      mainly focuses on trapping polysulfides at the cathode using various functional
      materials, few strategies are available at present to fully resolve or circumvent
      this long-standing issue. In this study, we propose the concept of sulfur
      equivalent cathode materials, and demonstrate the great potential of amorphous
      MoS3 as such a material for room-temperature Li-S and Na-S batteries. In Li-S
      batteries, MoS3 exhibits sulfur-like behavior with large reversible specific
      capacity, excellent cycle life, and the possibility to achieve high areal
      capacity. Most remarkably, it is also fully cyclable in the carbonate electrolyte
      under a relatively high temperature of 55  degrees C. MoS3 can also be used as
      the cathode material of even more challenging Na-S batteries to enable decent
      capacity and good cycle life. Operando X-ray absorption spectroscopy (XAS)
      experiments are carried out to track the structural evolution of MoS3 It largely
      preserves its chain-like structure during repetitive battery cycling without
      generating any free polysulfide intermediates.

PMID- 29180432
TI  - Phosphorylation of CENP-C by Aurora B facilitates kinetochore attachment error
      correction in mitosis.
AB  - Kinetochores are superprotein complexes that orchestrate chromosome segregation
      via a dynamic interaction with spindle microtubules. A physical connection
      between CENP-C and the Mis12-Ndc80-Knl1 (KMN) protein network is an important
      pathway that is used to assemble kinetochores on CENP-A nucleosomes. Multiple
      outer kinetochore components are phosphorylated by Aurora B kinase to activate
      the spindle assembly checkpoint (SAC) and to ensure accurate chromosome
      segregation. However, it is unknown whether Aurora B can phosphorylate inner
      kinetochore components to facilitate proper mitotic chromosome segregation. Here,
      we reported the structure of the fission yeast Schizosaccharomyces pombe Mis12
      Nnf1 complex and showed that N-terminal residues 26-50 in Cnp3 (the CENP-C
      homolog of S. pombe) are responsible for interacting with the Mis12 complex.
      Interestingly, Thr28 of Cnp3 is a substrate of Ark1 (the Aurora B homolog of S.
      pombe), and phosphorylation impairs the interaction between the Cnp3 and Mis12
      complex. The expression of a phosphorylation-mimicking Cnp3 mutant results in
      defective chromosome segregation due to improper kinetochore assembly. These
      results establish a previously uncharacterized regulatory mechanism involved in
      CENP-C-Mis12-facilitated kinetochore attachment error correction to ensure
      accurate chromosome segregation during mitosis.

PMID- 29180433
TI  - A STAT3-dependent transcriptional circuitry inhibits cytotoxic gene expression in
      T cells.
AB  - CD8+ T cells are preprogrammed for cytotoxic differentiation in the thymus as
      they acquire expression of the transcription factor Runx3. However, a subset of
      effector CD8+ T cells (Tc17) produce IL-17 and fail to express cytotoxic genes.
      Here, we show that the transcription factors directing IL-17 production, STAT3
      and RORgammat, inhibit cytotoxicity despite persistent Runx3 expression.
      Cytotoxic gene repression did not require the transcription factor Thpok, which
      in CD4+ T cells restrains Runx3 functions and cytotoxicity; and STAT3 restrained
      cytotoxic gene expression in CD8+ T cells responding to viral infection in vivo.
      STAT3-induced RORgammat represses cytotoxic genes by inhibiting the functions but
      not the expression of the "cytotoxic" transcription factors T-bet and
      Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression
      inhibits cytotoxic functions. However, by allowing expression of activators of
      the cytotoxic program, this inhibitory mechanism contributes to the instability
      of IL-17-producing T cells.

PMID- 29180434
TI  - Synaptic homeostasis requires the membrane-proximal carboxy tail of GluA2.
AB  - Bidirectional scaling of synaptic transmission, expressed as a compensatory
      change in quantal size following chronic activity perturbation, is a critical
      effector mechanism underlying homeostatic plasticity in the brain. An emerging
      model posits that the GluA2 AMPA receptor (AMPAR) subunit may be important for
      the bidirectional scaling of excitatory transmission; however, whether this
      subunit plays an obligatory role in synaptic scaling, and the identity of the
      precise domain(s) involved, remain controversial. We set out to determine the
      specific AMPAR subunit required for scaling up in CA1 hippocampal pyramidal
      neurons, and found that the GluA2 subunit is both necessary and sufficient. In
      addition, our results point to a critical role for a single amino acid within the
      membrane-proximal region of the GluA2 cytoplasmic tail, and suggest a distinct
      model for the regulation of AMPAR trafficking in synaptic homeostasis.

PMID- 29180435
TI  - Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1
      genomes during infection.
AB  - Numerous viruses, including HIV-1, exploit the microtubule network to traffic
      toward the nucleus during infection. Although numerous studies have observed a
      role for the minus-end microtubule motor dynein in HIV-1 infection, the mechanism
      by which the viral core containing the viral genome associates with dynein and
      induces its perinuclear trafficking has remained unclear. Here, we report that
      the dynein adapter protein bicaudal D2 (BICD2) is able to interact with HIV-1
      viral cores in target cells. We also observe that BICD2 can bind in vitro
      assembled capsid tubes through its CC3 domain. We observe that BICD2 facilitates
      infection by promoting the trafficking of viral cores to the nucleus, thereby
      promoting nuclear entry of the viral genome and infection. Finally, we observe
      that depletion of BICD2 in the monocytic cell line THP-1 results in an induction
      of IFN-stimulated genes in these cells. Collectively, these results identify a
      microtubule adapter protein critical for trafficking of HIV-1 in the cytoplasm of
      target cells and evasion of innate sensing mechanisms in macrophages.

PMID- 29180436
TI  - Broad detection of bacterial type III secretion system and flagellin proteins by
      the human NAIP/NLRC4 inflammasome.
AB  - Inflammasomes are cytosolic multiprotein complexes that initiate host defense
      against bacterial pathogens by activating caspase-1-dependent cytokine secretion
      and cell death. In mice, specific nucleotide-binding domain, leucine-rich repeat
      containing family, apoptosis inhibitory proteins (NAIPs) activate the nucleotide
      binding domain, leucine-rich repeat-containing family, CARD domain-containing
      protein 4 (NLRC4) inflammasome upon sensing components of the type III secretion
      system (T3SS) and flagellar apparatus. NAIP1 recognizes the T3SS needle protein,
      NAIP2 recognizes the T3SS inner rod protein, and NAIP5 and NAIP6 recognize
      flagellin. In contrast, humans encode a single functional NAIP, raising the
      question of whether human NAIP senses one or multiple bacterial ligands. Previous
      studies found that human NAIP detects both flagellin and the T3SS needle protein
      and suggested that the ability to detect both ligands was achieved by multiple
      isoforms encoded by the single human NAIP gene. Here, we show that human NAIP
      also senses the Salmonella Typhimurium T3SS inner rod protein PrgJ and that T3SS
      inner rod proteins from multiple bacterial species are also detected.
      Furthermore, we show that a single human NAIP isoform is capable of sensing the
      T3SS inner rod, needle, and flagellin. Our findings indicate that, in contrast to
      murine NAIPs, promiscuous recognition of multiple bacterial ligands is conferred
      by a single human NAIP.

PMID- 29180437
TI  - Solving visual correspondence between the two eyes via domain-based population
      encoding in nonhuman primates.
AB  - Stereoscopic vision depends on correct matching of corresponding features between
      the two eyes. It is unclear where the brain solves this binocular correspondence
      problem. Although our visual system is able to make correct global matches, there
      are many possible false matches between any two images. Here, we use optical
      imaging data of binocular disparity response in the visual cortex of awake and
      anesthetized monkeys to demonstrate that the second visual cortical area (V2) is
      the first cortical stage that correctly discards false matches and robustly
      encodes correct matches. Our findings indicate that a key transformation for
      achieving depth perception lies in early stages of extrastriate visual cortex and
      is achieved by population coding.

PMID- 29180439
TI  - Goodhart's law: when waiting times became a target, they stopped being a good
      measure.

PMID- 29180438
TI  - Protective effects of agonists of growth hormone-releasing hormone (GHRH) in
      early experimental diabetic retinopathy.
AB  - The potential therapeutic effects of agonistic analogs of growth hormone
      releasing hormone (GHRH) and their mechanism of action were investigated in
      diabetic retinopathy (DR). Streptozotocin-induced diabetic rats (STZ-rats) were
      treated with 15 MUg/kg GHRH agonist, MR-409, or GHRH antagonist, MIA-602. At the
      end of treatment, morphological and biochemical analyses assessed the effects of
      these compounds on retinal neurovascular injury induced by hyperglycemia. The
      expression levels of GHRH and its receptor (GHRH-R) measured by qPCR and Western
      blotting were significantly down-regulated in retinas of STZ-rats and in human
      diabetic retinas (postmortem) compared with their respective controls. Treatment
      of STZ-rats with the GHRH agonist, MR-409, prevented retinal morphological
      alteration induced by hyperglycemia, particularly preserving survival of retinal
      ganglion cells. The reverse, using the GHRH antagonist, MIA-602, resulted in
      worsening of retinal morphology and a significant alteration of the outer retinal
      layer. Explaining these results, we have found that MR-409 exerted antioxidant
      and anti-inflammatory effects in retinas of the treated rats, as shown by up
      regulation of NRF-2-dependent gene expression and down-regulation of
      proinflammatory cytokines and adhesion molecules. MR-409 also significantly down
      regulated the expression of vascular endothelial growth factor while increasing
      that of pigment epithelium-derived factor in diabetic retinas. These effects
      correlated with decreased vascular permeability. In summary, our findings suggest
      a neurovascular protective effect of GHRH analogs during the early stage of
      diabetic retinopathy through their antioxidant and anti-inflammatory properties.

PMID- 29180440
TI  - TIMP3 is a CLOCK-dependent diurnal gene that inhibits the expression of UVB
      induced inflammatory cytokines in human keratinocytes.
AB  - As the outermost physical barrier of an organism, the skin is diurnally exposed
      to UV radiation (UVR). Recent studies have revealed that the skin exhibits a
      circadian rhythm in various functions, and this oscillation is disturbed and
      reset via a strong environmental cue, the UVR. However, a molecular link between
      circadian perturbation by UVR and UVR-induced cellular responses has not been
      investigated. We identified tissue inhibitor of metalloproteinase ( TIMP)- 3 as a
      novel circadian locomotor output cycles kaput (CLOCK)-dependent diurnal gene by
      using a CLOCK-knockdown strategy in human keratinocytes. Among dozens of
      identified transcripts down-regulated by CLOCK knockdown, TIMP3 displayed a
      rhythmic expression in a CLOCK-dependent manner, in which the expression of
      matrix metalloproteinase (MMP)-1 and inflammatory cytokines, such as TNF-alpha,
      chemokine (C-X-C motif) ligand (CXCL)-1, and IL-8, were inversely regulated. Upon
      UVB exposure, the expression of CLOCK and TIMP3 was down-regulated, which led to
      an up-regulation of secretion of MMP1 and TNF-alpha proteins and in the
      transcription of CXCL1 and IL-8 via CCAAT-enhancer binding protein (C/EBP)-alpha.
      UVB-induced TNF-alpha secretion increased further or decreased by knockdown or
      overexpression of TIMP3, respectively, as well as by CLOCK. As a novel CLOCK
      dependent diurnal gene, TIMP3 inhibits the expression of inflammatory cytokines
      that are up-regulated by UV irradiation in human keratinocytes. Thus, our work
      suggests a molecular link between circadian perturbation by UVR and UVR-induced
      inflammation.-Park, S., Kim, K., Bae, I.-H., Lee, S. H., Jung, J., Lee, T. R.,
      Cho, E.-G. TIMP3 is a CLOCK-dependent diurnal gene that inhibits the expression
      of UVB-induced inflammatory cytokines in human keratinocytes.

PMID- 29180441
TI  - Neural deletion of Sh2b1 results in brain growth retardation and reactive
      aggression.
AB  - Psychiatric disorders are associated with aberrant brain development and/or
      aggressive behavior and are influenced by genetic factors; however, genes that
      affect brain aggression circuits remain elusive. Here, we show that neuronal Src
      homology-2 (SH2)B adaptor protein-1 ( Sh2b1) is indispensable for both brain
      growth and protection against aggression. Global and brain-specific deletion of
      Sh2b1 decreased brain weight and increased aggressive behavior. Global and brain
      specific Sh2b1 knockout (KO) mice exhibited fatal, intermale aggression. In a
      resident-intruder paradigm, latency to attack was markedly reduced, whereas the
      number and the duration of attacks was significantly increased in global and
      brain-specific Sh2b1 KO mice compared with wild-type littermates. Consistently,
      core aggression circuits were activated to a higher level in global and brain
      specific Sh2b1 KO males, based on c-fos immunoreactivity in the amygdala and
      periaqueductal gray. Brain-specific restoration of Sh2b1 normalized brain size
      and reversed pathologic aggression and aberrant activation of core aggression
      circuits in Sh2b1 KO males. SH2B1 mutations in humans were linked to aberrant
      brain development and behavior. At the molecular level, Sh2b1 enhanced
      neurotrophin-stimulated neuronal differentiation and protected against oxidative
      stress-induced neuronal death. Our data suggest that neuronal Sh2b1 promotes
      brain development and the integrity of core aggression circuits, likely through
      enhancing neurotrophin signaling.-Jiang, L., Su, H., Keogh, J. M., Chen, Z.,
      Henning, E., Wilkinson, P., Goodyer, I., Farooqi, I. S., Rui, L. Neural deletion
      of Sh2b1 results in brain growth retardation and reactive aggression.

PMID- 29180442
TI  - KCa2 channel localization and regulation in the axon initial segment.
AB  - Small conductance calcium-activated potassium (KCa2) channels are expressed
      throughout the CNS and play a critical role in synaptic and neuronal
      excitability. KCa2 channels have a somatodendritic distribution with their
      highest expression in distal dendrites. It is unclear whether KCa2 channels are
      specifically present on the axon initial segment (AIS), the site at which action
      potentials are initiated in neurons. Through a powerful combination of toxin
      pharmacology, single-molecule atomic force microscopy, and dual-color
      fluorescence microscopy, we report here that KCa2 channels-predominantly the
      KCa2.3 subtype-are indeed present on the AIS. We also report that cAMP-PKA
      controls the axonal KCa2 channel surface expression. Surprisingly, and in
      contrast to KCa2 channels that were observed in the soma and dendrites, the
      inhibition of cAMP-PKA increased the surface expression of KCa2 channels without
      promoting nanoclustering. Lastly, we found that axonal KCa2 channels seem to
      undergo endocytosis in a dynamin-independent manner, unlike KCa2 channels in the
      soma and dendrites. Together, these novel results demonstrate that the
      distribution and membrane recycling of KCa2 channels differs among various
      neuronal subcompartments.-Abiraman, K., Tzingounis, A. V., Lykotrafitis, G. KCa2
      channel localization and regulation in the axon initial segment.

PMID- 29180443
TI  - Genomic and lipidomic analyses differentiate the compensatory roles of two COX
      isoforms during systemic inflammation in mice.
AB  - Both cyclooxygenase (COX)-1 and COX-2, encoded by Ptgs1 and Ptgs2, function
      coordinately during inflammation. But the relative contributions and
      compensations of COX-1 and COX-2 to inflammatory responses remain unanswered. We
      used three engineered mouse lines where the Ptgs1 and Ptgs2 genes substitute for
      one another to discriminate the distinct roles and interchangeability of COX
      isoforms during systemic inflammation. In macrophages, kidneys, and lungs,
      "flipped" Ptgs genes generate a "reversed" COX expression pattern, where the
      knock-in COX-2 is expressed constitutively and the knock-in COX-1 is
      lipopolysaccharide inducible. A panel of eicosanoids detected in serum and kidney
      demonstrates that prostaglandin (PG) biosynthesis requires native COX-1 and
      cannot be rescued by the knock-in COX-2. Our data further reveal preferential
      compensation of COX isoforms for prostanoid production in macrophages and
      throughout the body, as reflected by urinary PG metabolites. NanoString analysis
      indicates that inflammatory networks can be maintained by isoform substitution in
      inflamed macrophages. However, COX-1>COX-2 macrophages show reduced activation of
      inflammatory signaling pathways, indicating that COX-1 may be replaced by COX-2
      within this complex milieu, but not vice versa. Collectively, each COX isoform
      plays a distinct role subject to subcellular environment and tissue/cell-specific
      conditions, leading to subtle compensatory differences during systemic
      inflammation.

PMID- 29180444
TI  - PCSK9 deficiency reduces atherosclerosis, apolipoprotein B secretion, and
      endothelial dysfunction.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) interacts directly with
      cytoplasmic apoB and prevents its degradation via the autophagosome/lysosome
      pathway. This process affects VLDL and LDL production and influences
      atherogenesis. Here, we investigated the molecular machinery by which PCSK9
      modulates autophagy and affects atherogenesis. We backcrossed Pcsk9-/- mice with
      atherosclerosis-prone Ldlr-/-Apobec1-/- (LDb) mice to generate Ldlr-/-Apobec1-/
      Pcsk9-/- (LTp) mice. Deletion of PCSK9 resulted in decreased hepatic apoB
      secretion, increased autophagic flux, and decreased plasma levels of IDL and LDL
      particles. The LDLs from LTp mice (LTp-LDLs) were less atherogenic and contained
      less cholesteryl ester and phospholipids than LDb-LDLs. Moreover LTp-LDLs induced
      lower endothelial expression of the genes encoding TLR2, Lox-1, ICAM-1, CCL2,
      CCL7, IL-6, IL-1beta, Beclin-1, p62, and TRAF6 Collectively, these effects were
      associated with substantially less atherosclerosis development (>4-fold) in LTp
      mice. The absence of PCSK9 in LDb mice results in decreased lipid and apoB
      levels, fewer atherogenic LDLs, and marked reduction of atherosclerosis. The
      effect on atherogenesis may be mediated in part by the effects of modified LDLs
      on endothelial cell receptors and proinflammatory and autophagy molecules. These
      findings suggest that there may be clinical benefits of PCSK9 inhibition due to
      mechanisms unrelated to increased LDL receptor activity.

PMID- 29180445
TI  - Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific compensatory
      functions.
AB  - Two prostaglandin (PG) H synthases encoded by Ptgs genes, colloquially known as
      cyclooxygenase (COX)-1 and COX-2, catalyze the formation of PG endoperoxide H2,
      the precursor of the major prostanoids. To address the functional
      interchangeability of these two isoforms and their distinct roles, we have
      generated COX-2>COX-1 mice whereby Ptgs2 is knocked in to the Ptgs1 locus. We
      then "flipped" Ptgs genes to successfully create the Reversa mouse strain, where
      knock-in COX-2 is expressed constitutively and knock-in COX-1 is
      lipopolysaccharide (LPS) inducible. In macrophages, flipping the two Ptgs genes
      has no obvious impact on COX protein subcellular localization. COX-1 was shown to
      compensate for PG synthesis at high concentrations of substrate, whereas elevated
      LPS-induced PG production was only observed for cells expressing endogenous COX
      2. Differential tissue-specific patterns of expression of the knock-in proteins
      were evident. Thus, platelets from COX-2>COX-1 and Reversa mice failed to express
      knock-in COX-2 and, therefore, thromboxane (Tx) production in vitro and urinary
      Tx metabolite formation in COX-2>COX-1 and Reversa mice in vivo were
      substantially decreased relative to WT and COX-1>COX-2 mice. Manipulation of COXs
      revealed isoform-specific compensatory functions and variable degrees of
      interchangeability for PG biosynthesis in cells/tissues.

PMID- 29180446
TI  - Quantitative ligand and receptor binding studies reveal the mechanism of
      interleukin-36 (IL-36) pathway activation.
AB  - IL-36 cytokines signal through the IL-36 receptor (IL-36R) and a shared subunit,
      IL-1RAcP (IL-1 receptor accessory protein). The activation mechanism for the IL
      36 pathway is proposed to be similar to that of IL-1 in that an IL-36R agonist
      (IL-36alpha, IL-36beta, or IL-36gamma) forms a binary complex with IL-36R, which
      then recruits IL-1RAcP. Recent studies have shown that IL-36R interacts with IL
      1RAcP even in the absence of an agonist. To elucidate the IL-36 activation
      mechanism, we considered all possible binding events for IL-36 ligands/receptors
      and examined these events in direct binding assays. Our results indicated that
      the agonists bind the IL-36R extracellular domain with micromolar affinity but do
      not detectably bind IL-1RAcP. Using surface plasmon resonance (SPR), we found
      that IL-1RAcP also does not bind IL-36R when no agonist is present. In the
      presence of IL-36alpha, however, IL-1RAcP bound IL-36R strongly. These results
      suggested that the main pathway to the IL-36R.IL-36alpha.IL-1RAcP ternary complex
      is through the IL-36R.IL-36alpha binary complex, which recruits IL-1RAcP. We
      could not measure the binding affinity of IL-36R to IL-1RAcP directly, so we
      engineered a fragment crystallizable-linked construct to induce IL-36R.IL-1RAcP
      heterodimerization and predicted the binding affinity during a complete
      thermodynamic cycle to be 74 MUm The SPR analysis also indicated that the IL-36R
      antagonist IL-36Ra binds IL-36R with higher affinity and a much slower off rate
      than the IL-36R agonists, shedding light on IL-36 pathway inhibition. Our results
      reveal the landscape of IL-36 ligand and receptor interactions, improving our
      understanding of IL-36 pathway activation and inhibition.

PMID- 29180447
TI  - A variant of death-receptor 3 associated with rheumatoid arthritis interferes
      with apoptosis-induction of T cell.
AB  - Rheumatoid arthritis (RA) is a chronic polyarthritis of unknown etiology. To
      unravel the molecular mechanisms in RA, we performed targeted DNA sequencing
      analysis of patients with RA. This analysis identified a variant of the death
      receptor 3 (DR3) gene, a member of the family of apoptosis-inducing Fas genes,
      which contains four single-nucleotide polymorphisms (SNPs) and a 14-nucleotide
      deletion within exon 5 and intron 5. We found that the deletion causes the
      binding of splicing regulatory proteins to DR3 pre-mRNA intron 5, resulting in a
      portion of intron 5 becoming part of the coding sequence, thereby generating a
      premature stop codon. We also found that this truncated DR3 protein product lacks
      the death domain and forms a heterotrimer complex with wildtype DR3 that dominant
      negatively inhibits ligand-induced apoptosis in lymphocytes. Myelocytes from
      transgenic mice expressing the human DR3 variant produced soluble truncated DR3,
      forming a complex with TNF-like ligand 1A (TL1A), which inhibited apoptosis
      induction. In summary, our results reveal that a DR3 splice variant that
      interferes with ligand-induced T cell responses and apoptosis may contribute to
      RA pathogenesis.

PMID- 29180448
TI  - A neutralizing antibody that blocks delivery of the enzymatic cargo of
      Clostridium difficile toxin TcdB into host cells.
AB  - Clostridium difficile infection is the leading cause of hospital-acquired
      diarrhea and is mediated by the actions of two toxins, TcdA and TcdB. The toxins
      perturb host cell function through a multistep process of receptor binding,
      endocytosis, low pH-induced pore formation, and the translocation and delivery of
      an N-terminal glucosyltransferase domain that inactivates host GTPases. Infection
      studies with isogenic strains having defined toxin deletions have established
      TcdB as an important target for therapeutic development. Monoclonal antibodies
      that neutralize TcdB function have been shown to protect against C. difficile
      infection in animal models and reduce recurrence in humans. Here, we report the
      mechanism of TcdB neutralization by PA41, a humanized monoclonal antibody capable
      of neutralizing TcdB from a diverse array of C. difficile strains. Through a
      combination of structural, biochemical, and cell functional studies, involving X
      ray crystallography and EM, we show that PA41 recognizes a single, highly
      conserved epitope on the TcdB glucosyltransferase domain and blocks productive
      translocation and delivery of the enzymatic cargo into the host cell. Our study
      reveals a unique mechanism of C. difficile toxin neutralization by a monoclonal
      antibody, which involves targeting a process that is conserved across the large
      clostridial glucosylating toxins. The PA41 antibody described here provides a
      valuable tool for dissecting the mechanism of toxin pore formation and
      translocation across the endosomal membrane.

PMID- 29180449
TI  - Ligand-specific conformational transitions and intracellular transport are
      required for atypical chemokine receptor 3-mediated chemokine scavenging.
AB  - The atypical chemokine receptor ACKR3 contributes to chemotaxis by binding,
      internalizing, and degrading the chemokines CXCL11 and CXCL12 to shape and
      terminate chemotactic gradients during development and immune responses. Although
      unable to trigger G protein activation, both ligands activate G protein
      independent ACKR3 responses and prompt arrestin recruitment. This offers a model
      to specifically study ligand-specific receptor conformations leading to G protein
      independent signaling and to functional parameters such as receptor transport and
      chemokine degradation. We here show chemokine specificity in arrestin
      recruitment, by different effects of single amino acid substitutions in ACKR3 on
      arrestin in response to CXCL12 or CXCL11. Chemokine specificity in receptor
      transport was also observed, as CXCL11 induced faster receptor internalization,
      slower recycling, and longer intracellular sojourn of ACKR3 than CXCL12.
      Internalization and recycling rates of the ACKR3 R1423.50A substitution in
      response to each chemokine were similar; however, ACKR3 R1423.50A degraded only
      CXCL12 and not CXCL11. This suggests that ligand-specific intracellular receptor
      transport is required for chemokine degradation. Remarkably, the failure of ACKR3
      R1423.50A to degrade CXCL11 was not caused by the lack of arrestin recruitment;
      rather, arrestin was entirely dispensable for scavenging of either chemokine.
      This suggests the involvement of another, yet unidentified, ACKR3 effector in
      scavenging. In summary, our study correlates ACKR3 ligand-specific conformational
      transitions with chemokine-dependent receptor transport dynamics and points
      toward unexpected ligand specificity in the mechanisms of chemokine degradation.

PMID- 29180450
TI  - Knockout of mitochondrial voltage-dependent anion channel type 3 increases
      reactive oxygen species (ROS) levels and alters renal sodium transport.
AB  - It has been suggested that voltage-dependent anion channels (VDACs) control the
      release of superoxide from mitochondria. We have previously shown that reactive
      oxygen species (ROS) such as superoxide (O2) and hydrogen peroxide (H2O2)
      stimulate epithelial sodium channels (ENaCs) in sodium-transporting epithelial
      tissue, including cortical collecting duct (CCD) principal cells. Therefore, we
      hypothesized that VDACs could regulate ENaC by modulating cytosolic ROS levels.
      Herein, we find that VDAC3-knockout(KO) mice can maintain normal salt and water
      balance on low-salt and high-salt diets. However, on a high-salt diet for 2
      weeks, VDAC3-KO mice had significantly higher systolic blood pressure than
      wildtype mice. Consistent with this observation, after a high-salt diet for 2
      weeks, ENaC activity in VDAC3-KO mice was significantly higher than wildtype
      mice. EM analysis disclosed a significant morphological change of mitochondria in
      the CCD cells of VDAC3-KO mice compared with wildtype mice, which may have been
      caused by mitochondrial superoxide overload. Of note, compared with wildtype
      animals, ROS levels in VDAC3-KO animals fed a normal or high-salt diet were
      consistently and significantly increased in renal tubules. Both the ROS scavenger
      1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (TEMPOL) and the mitochondrial ROS
      scavenger (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2
      oxoethyl)triphenylphosphonium chloride (mito-TEMPO) could reverse the effect of
      high-salt on ENaC activity and systolic blood pressure in the VDAC3-KO mice. Mito
      TEMPO partially correct the morphological changes in VDAC3-KO mice. Our results
      suggest that knocking out mitochondrial VDAC3 increases ROS, alters renal sodium
      transport, and leads to hypertension.

PMID- 29180451
TI  - Molecular mimicking of C-terminal phosphorylation tunes the surface dynamics of
      CaV1.2 calcium channels in hippocampal neurons.
AB  - L-type voltage-gated CaV1.2 calcium channels (CaV1.2) are key regulators of
      neuronal excitability, synaptic plasticity, and excitation-transcription
      coupling. Surface-exposed CaV1.2 distributes in clusters along the dendrites of
      hippocampal neurons. A permanent exchange between stably clustered and laterally
      diffusive extra-clustered channels maintains steady-state levels of CaV1.2 at
      dendritic signaling domains. A dynamic equilibrium between anchored and diffusive
      receptors is a common feature among ion channels and is crucial to modulate
      signaling transduction. Despite the importance of this fine regulatory system,
      the molecular mechanisms underlying the surface dynamics of CaV1.2 are completely
      unexplored. Here, we examined the dynamic states of CaV1.2 depending on
      phosphorylation on Ser-1700 and Ser-1928 at the channel C terminus.
      Phosphorylation at these sites is strongly involved in CaV1.2-mediated nuclear
      factor of activated T cells (NFAT) signaling, long-term potentiation, and
      responsiveness to adrenergic stimulation. We engineered CaV1.2 constructs
      mimicking phosphorylation at Ser-1700 and Ser-1928 and analyzed their behavior at
      the membrane by immunolabeling protocols, fluorescence recovery after
      photobleaching, and single particle tracking. We found that the phosphomimetic
      S1928E variant increases the mobility of CaV1.2 without altering the steady-state
      maintenance of cluster in young neurons and favors channel stabilization later in
      differentiation. Instead, mimicking phosphorylation at Ser-1700 promoted the
      diffusive state of CaV1.2 irrespective of the differentiation stage. Together,
      these results reveal that phosphorylation could contribute to the establishment
      of channel anchoring mechanisms depending on the neuronal differentiation state.
      Finally, our findings suggest a novel mechanism by which phosphorylation at the C
      terminus regulates calcium signaling by tuning the content of CaV1.2 at signaling
      complexes.

PMID- 29180452
TI  - Conformational switch of the bacterial adhesin FimH in the absence of the
      regulatory domain: Engineering a minimalistic allosteric system.
AB  - For many biological processes such as ligand binding, enzymatic catalysis, or
      protein folding, allosteric regulation of protein conformation and dynamics is
      fundamentally important. One example is the bacterial adhesin FimH, where the C
      terminal pilin domain exerts negative allosteric control over binding of the N
      terminal lectin domain to mannosylated ligands on host cells. When the lectin and
      pilin domains are separated under shear stress, the FimH-ligand interaction
      switches in a so-called catch-bond mechanism from the low- to high-affinity
      state. So far, it has been assumed that the pilin domain is essential for the
      allosteric propagation within the lectin domain that would otherwise be
      conformationally rigid. To test this hypothesis, we generated mutants of the
      isolated FimH lectin domain and characterized their thermodynamic, kinetic, and
      structural properties using isothermal titration calorimetry, surface plasmon
      resonance, nuclear magnetic resonance, and X-ray techniques. Intriguingly, some
      of the mutants mimicked the conformational and kinetic behaviors of the full
      length protein and, even in absence of the pilin domain, conducted the cross-talk
      between allosteric sites and the mannoside-binding pocket. Thus, these mutants
      represent a minimalistic allosteric system of FimH, useful for further
      mechanistic studies and antagonist design.

PMID- 29180455
TI  - Hypertension: Update 2018.

PMID- 29180453
TI  - A hereditary spastic paraplegia-associated atlastin variant exhibits defective
      allosteric coupling in the catalytic core.
AB  - The dynamin-related GTPase atlastin (ATL) catalyzes membrane fusion of the
      endoplasmic reticulum and thus establishes a network of branched membrane
      tubules. When ATL function is compromised, the morphology of the endoplasmic
      reticulum deteriorates, and these defects can result in neurological disorders
      such as hereditary spastic paraplegia and hereditary sensory neuropathy. ATLs
      harness the energy of GTP hydrolysis to initiate a series of conformational
      changes that enable homodimerization and subsequent membrane fusion. Disease
      associated amino acid substitutions cluster in regions adjacent to ATL's
      catalytic site, but the consequences for the GTPase's molecular mechanism are
      often poorly understood. Here, we elucidate structural and functional defects of
      an atypical hereditary spastic paraplegia mutant, ATL1-F151S, that is impaired in
      its nucleotide-hydrolysis cycle but can still adopt a high-affinity homodimer
      when bound to a transition-state analog. Crystal structures of mutant proteins
      yielded models of the monomeric pre- and post-hydrolysis states of ATL. Together,
      these findings define a mechanism for allosteric coupling in which Phe151 is the
      central residue in a hydrophobic interaction network connecting the active site
      to an interdomain interface responsible for nucleotide loading.

PMID- 29180454
TI  - Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients
      With Obesity and Hypertension.
AB  - : Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin
      inhibitor, was recently approved for the treatment of heart failure with reduced
      ejection fraction. Neprilysin degrades several peptides that modulate lipid
      metabolism, including natriuretic peptides. In this study, we investigated the
      effects of 8 weeks' treatment with sacubitril/valsartan on whole-body and adipose
      tissue lipolysis and lipid oxidation during defined physical exercise compared
      with the metabolically neutral comparator amlodipine. This was a multicenter,
      randomized, double-blind, active-controlled, parallel-group study enrolling
      subjects with abdominal obesity and moderate hypertension (mean sitting systolic
      blood pressure >=130-180 mm Hg). Lipolysis during rest and exercise was assessed
      by microdialysis and [1,1,2,3,3-2H]-glycerol tracer kinetics. Energy expenditure
      and substrate oxidation were measured simultaneously using indirect calorimetry.
      Plasma nonesterified fatty acids, glycerol, insulin, glucose, adrenaline and
      noradrenaline concentrations, blood pressure, and heart rate were also
      determined. Exercise elevated plasma glycerol, free fatty acids, and interstitial
      glycerol concentrations and increased the rate of glycerol appearance. However,
      exercise-induced stimulation of lipolysis was not augmented on
      sacubitril/valsartan treatment compared with amlodipine treatment. Furthermore,
      sacubitril/valsartan did not alter energy expenditure and substrate oxidation
      during exercise compared with amlodipine treatment. In conclusion,
      sacubitril/valsartan treatment for 8 weeks did not elicit clinically relevant
      changes in exercise-induced lipolysis or substrate oxidation in obese patients
      with hypertension, implying that its beneficial cardiovascular effects cannot be
      explained by changes in lipid metabolism during exercise. CLINICAL TRIAL
      REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
      NCT01631864.

PMID- 29180456
TI  - Body Mass Index and Vascular Disease in Men Aged 65 Years and Over: HIMS (Health
      In Men Study).
AB  - BACKGROUND: Understanding the relationship between body mass index (BMI) and
      vascular disease at older age has become increasingly important in the many
      countries where both average age and BMI are rising. METHODS AND RESULTS: In this
      prospective cohort study, 12 203 men (aged >=65) were recruited in 1996-1999 from
      the general population in Perth, Australia. To limit reverse causality, analyses
      excluded those with past vascular disease and the first 4 years of follow-up.
      During a further 8 (SD3) years of follow-up, there were 1136 first-ever major
      vascular events (nonfatal myocardial infarction, nonfatal stroke, or death from
      any vascular cause). Cox regression (adjusted for age, education, and smoking)
      related BMI at recruitment to incidence of major vascular events. At ages 65 to
      94, the lowest risk of major vascular events was at ~ 22.5 to 25 kg/m2. In the
      higher BMI range (>=25 kg/m2), 5 kg/m2 higher BMI was associated with 33% higher
      risk of major vascular events (hazard ratio, 1.33 [95% confidence interval, 1.18
      1.49]): 24% higher risk of ischemic heart disease (1.24 [1.06-1.46]); 34% higher
      risk of stroke (1.34 [1.11-1.63]); and 78% higher risk of other vascular death
      (1.78 [1.32-2.41]). In the lower BMI range, there were fewer events and no strong
      evidence of an association (hazard ratio per 5 kg/m2 higher BMI, 0.82 [95%
      confidence interval, 0.61-1.12]). CONCLUSIONS: In this population of older men,
      risk of major vascular events was lowest at ~ 22.5 to 25 kg/m2. Above this range,
      BMI was strongly related to incidence of major vascular events, with each 5 kg/m2
      higher BMI associated with ~30% higher risk.

PMID- 29180459
TI  - Inpatient bedspacing: could a common response to hospital crowding cause
      increased patient mortality?

PMID- 29180458
TI  - Clinical Outcomes After Ablation of the AV Junction in Patients With Atrial
      Fibrillation: Impact of Cardiac Resynchronization Therapy.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) often undergo AV junction
      ablation (AVJA) and pacemaker implantation. Right ventricular (RV) pacing
      contributes to increased risk of heart failure (HF), which may be mitigated by
      biventricular pacing. We sought to determine the impact of AVJA concurrent with
      RV versus biventricular pacemaker implantation on AF and HF hospitalizations.
      METHODS AND RESULTS: The MarketScan Commercial and Medicare Supplemental claims
      database was used to select 18- to 100-year-old patients with AF with pacemaker
      implantation. Patients were divided into those with an RV and a biventricular
      pacemaker and further into those who did (AVJA+) or did not undergo concurrent
      ablation. Separately, the AVJA+ group was divided into those receiving RV versus
      biventricular pacemakers. AF and HF hospitalization rates were compared between
      groups after matching on demographics, comorbidities, and baseline
      hospitalization rates. The study included 24 361 patients, with RV (n=23 377) or
      biventricular (n=984) pacemakers; 1611 patients underwent AVJA. AVJA+ was
      associated with reduced AF hospitalization risk (RV hazard ratio [HR], 0.31;
      P<0.001; biventricular HR, 0.20; P=0.003) compared with no AVJA. However, HF
      hospitalization risk was increased for RV (HR, 1.63; P=0.001), but not
      biventricular (HR, 0.98; P=0.942), pacemakers. In AVJA+ patients, biventricular
      pacing was associated with reduced risk of HF hospitalization versus RV pacing
      (HR, 0.62; P=0.017). CONCLUSIONS: In a large cohort of patients with AF, AVJA+
      significantly reduced AF hospitalizations, irrespective of whether an RV or a
      biventricular pacemaker was implanted. However, AVJA was associated with a marked
      HF hospitalization increase in patients with an RV pacemaker, which was
      ameliorated with biventricular pacing.

PMID- 29180457
TI  - Antihypertensive Treatment With beta-Blockade in Patients With Asymptomatic
      Aortic Stenosis and Association With Cardiovascular Events.
AB  - BACKGROUND: Patients with aortic stenosis (AS) often have concomitant
      hypertension. Antihypertensive treatment with a beta-blocker (Bbl) is frequently
      avoided because of fear of depression of left ventricular function. However, it
      remains unclear whether antihypertensive treatment with a Bbl is associated with
      increased risk of cardiovascular events in patients with asymptomatic mild to
      moderate AS. METHODS AND RESULTS: We did a post hoc analysis of 1873 asymptomatic
      patients with mild to moderate AS and preserved left ventricular ejection
      fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study.
      Propensity-matched Cox regression and competing risk analyses were used to assess
      risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular
      death. A total of 932 (50%) patients received Bbl at baseline. During a median
      follow-up of 4.3+/-0.9 years, 545 underwent aortic valve replacement, and 205
      died; of those, 101 were cardiovascular deaths, including 40 sudden
      cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower
      risk of all-cause mortality (hazard ratio 0.5, 95% confidence interval 0.3-0.7,
      P<0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2
      0.7, P<0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence
      interval 0.1-0.6, P=0.004). This was confirmed in competing risk analyses (all
      P<0.004). No interaction was detected with AS severity (all P>0.1). CONCLUSIONS:
      In post hoc analyses Bbl therapy did not increase the risk of all-cause
      mortality, sudden cardiac death, or cardiovascular death in patients with
      asymptomatic mild to moderate AS. A prospective study may be warranted to
      determine if Bbl therapy is in fact beneficial. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

PMID- 29180460
TI  - Accelerating Early Access to Immunotherapies for Advanced Urothelial Carcinoma.

PMID- 29180461
TI  - Weapon Carrying Among Victims of Bullying.
AB  - OBJECTIVES: To examine, in a large, nationally representative sample of high
      school students, the association between bullying victimization and carrying
      weapons to school and to determine to what extent past experience of 1, 2, or 3
      additional indicators of peer aggression increases the likelihood of weapon
      carrying by victims of bullying (VoBs). METHODS: National data from the 2015
      Youth Risk Behavior Survey were analyzed for grades 9 to 12 (N = 15 624). VoB
      groups were determined by self-report of being bullied at school and additional
      adverse experiences: fighting at school, being threatened or injured at school,
      and skipping school out of fear for one's safety. Weapon carrying was measured by
      a dichotomized (ie, >=1 vs 0) report of carrying a gun, knife, or club on school
      property. VoB groups were compared with nonvictims with respect to weapon
      carrying by logistic regression adjusting for sex, grade, and race/ethnicity.
      RESULTS: When surveyed, 20.2% of students reported being a VoB in the past year,
      and 4.1% reported carrying a weapon to school in the past month. VoBs
      experiencing 1, 2, or 3 additional risk factors were successively more likely to
      carry weapons to school. The subset of VoBs who experienced all 3 additional
      adverse experiences were more likely to carry weapons to school compared with
      nonvictims (46.4% vs 2.5%, P < .001). CONCLUSIONS: Pediatricians should recognize
      that VoBs, especially those who have experienced 1 or more indicators of peer
      aggression in conjunction, are at substantially increased risk of weapon
      carrying.

PMID- 29180462
TI  - Global Human Trafficking and Child Victimization.
AB  - Trafficking of children for labor and sexual exploitation violates basic human
      rights and constitutes a major global public health problem. Pediatricians and
      other health care professionals may encounter victims who present with
      infections, injuries, posttraumatic stress disorder, suicidality, or a variety of
      other physical or behavioral health conditions. Preventing child trafficking,
      recognizing victimization, and intervening appropriately require a public health
      approach that incorporates rigorous research on the risk factors, health impact,
      and effective treatment options for child exploitation as well as implementation
      and evaluation of primary prevention programs. Health care professionals need
      training to recognize possible signs of exploitation and to intervene
      appropriately. They need to adopt a multidisciplinary, outward-focused approach
      to service provision, working with nonmedical professionals in the community to
      assist victims. Pediatricians also need to advocate for legislation and policies
      that promote child rights and victim services as well as those that address the
      social determinants of health, which influence the vulnerability to human
      trafficking. This policy statement outlines major issues regarding public policy,
      medical education, research, and collaboration in the area of child labor and sex
      trafficking and provides recommendations for future work.

PMID- 29180463
TI  - Trends of Out-of-Hospital Sudden Cardiac Death Among Children and Young Adults.
AB  - BACKGROUND AND OBJECTIVES: Previous estimates of sudden cardiac death in children
      and young adults vary significantly, and population-based studies in the United
      States are lacking. We sought to estimate the incidence, causes, and mortality
      trends of sudden cardiac death in children and young adults (1-34 years).
      METHODS: Demographic and mortality data based on death certificates for US
      residents (1-34 years) were obtained (1999-2015). Cases of sudden death and
      sudden cardiac death were retrieved by using the International Classification of
      Diseases, 10th Revision codes. RESULTS: A total of 1 452 808 subjects aged 1 to
      34 years died in the United States, of which 31 492 (2%) were due to sudden
      cardiac death. The estimated incidence of sudden cardiac death is 1.32 per 100
      000 individuals and increased with age from 0.49 (1-10 years) to 2.76 (26-34
      years). During the study period, incidence of sudden cardiac death declined from
      1.48 to 1.13 per 100 000 (P < .001). Mortality reduction was observed across all
      racial and ethnic groups with a varying magnitude and was highest in children
      aged 11 to 18 years. Significant disparities were found, with non-Hispanic
      African American individuals and individuals aged 26 to 34 years having the
      highest mortality rates. The majority of young children (1-10 years) died of
      congenital heart disease (n = 1525, 46%), whereas young adults died most commonly
      from ischemic heart disease (n = 5075, 29%). CONCLUSIONS: Out-of-hospital sudden
      cardiac death rates declined 24% from 1999 to 2015. Disparities in mortality
      exist across age groups and racial and ethnic groups, with non-Hispanic African
      American individuals having the highest mortality rates.

PMID- 29180464
TI  - Sudden Cardiac Death Decreasing: Why Remains Unclear.

PMID- 29180465
TI  - Complexities in the Association Between Bullying Victimization and Weapon
      Carrying.

PMID- 29180466
TI  - Synthetic Lethality of PARP Inhibitors in Combination with MYC Blockade Is
      Independent of BRCA Status in Triple-Negative Breast Cancer.
AB  - PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients.
      Several of those patients exhibit intrinsic/acquired resistance mechanisms that
      limit efficacy of PARPi monotherapy. Here we show how the efficacy of PARPi in
      triple-negative breast cancers (TNBC) can be expanded by targeting MYC-induced
      oncogenic addiction. In BRCA-mutant/sporadic TNBC patients, amplification of the
      MYC gene is correlated with increased expression of the homologous DNA
      recombination enzyme RAD51 and tumors overexpressing both genes are associated
      with worse overall survival. Combining MYC blockade with PARPi yielded synthetic
      lethality in MYC-driven TNBC cells. Using the cyclin-dependent kinase inhibitor
      dinaciclib, which downregulates MYC expression, we found that combination with
      the PARPi niraparib increased DNA damage and downregulated homologous
      recombination, leading to subsequent downregulation of the epithelial-mesenchymal
      transition and cancer stem-like cell phenotypes. Notably, dinaciclib resensitized
      TBNC cells, which had acquired resistance to niraparib. We found that the
      synthetic lethal strategy employing dinaciclib and niraparib was also highly
      efficacious in ovarian, prostate, pancreatic, colon, and lung cancer cells. Taken
      together, our results show how blunting MYC oncogene addiction can leverage
      cancer cell sensitivity to PARPi, facilitating the clinical use of c-myc as a
      predictive biomarker for this treatment.Significance: Dual targeting of MYC
      regulated homologous recombination and PARP-mediated DNA repair yields potent
      synthetic lethality in triple-negative breast tumors and other aggressive tumors
      characterized by MYC overexpression. Cancer Res; 78(3); 742-57. (c)2017 AACR.

PMID- 29180467
TI  - YAP1 and COX2 Coordinately Regulate Urothelial Cancer Stem-like Cells.
AB  - Overcoming acquired drug resistance remains a core challenge in the clinical
      management of human cancer, including in urothelial carcinoma of the bladder
      (UCB). Cancer stem-like cells (CSC) have been implicated in the emergence of drug
      resistance but mechanisms and intervention points are not completely understood.
      Here, we report that the proinflammatory COX2/PGE2 pathway and the YAP1 growth
      regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding
      and sustaining the accumulation of urothelial CSCs. Mechanistically, COX2/PGE2
      signaling induced promoter methylation of let-7, resulting in its downregulation
      and subsequent SOX2 upregulation. YAP1 induced SOX2 expression more directly by
      binding its enhancer region. In UCB clinical specimens, positive correlations in
      the expression of SOX2, COX2, and YAP1 were observed, with coexpression of COX2
      and YAP1 particularly commonly observed. Additional investigations suggested that
      activation of the COX2/PGE2 and YAP1 pathways also promoted acquired resistance
      to EGFR inhibitors in basal-type UCB. In a mouse xenograft model of UCB, dual
      inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by
      limiting CSC expansion after chemotherapy and EGFR inhibition. Our findings
      provide a preclinical rationale to target these pathways concurrently with
      systemic chemotherapy as a strategy to improve the clinical management of
      UCB.Significance: These findings offer a preclinical rationale to target the COX2
      and YAP1 pathways concurrently with systemic chemotherapy to improve the clinical
      management of UCB, based on evidence that these two pathways expand cancer stem
      like cell populations that mediate resistance to chemotherapy. Cancer Res; 78(1);
      168-81. (c)2017 AACR.

PMID- 29180468
TI  - Small-Molecule Inhibition of Axl Targets Tumor Immune Suppression and Enhances
      Chemotherapy in Pancreatic Cancer.
AB  - Activation of the receptor tyrosine kinase Axl is associated with poor outcomes
      in pancreatic cancer (PDAC), where it coordinately mediates immune evasion and
      drug resistance. Here, we demonstrate that the selective Axl kinase inhibitor
      BGB324 targets the tumor-immune interface to blunt the aggressive traits of PDAC
      cells in vitro and enhance gemcitibine efficacy in vivo Axl signaling stimulates
      the TBK1-NFkappaB pathway and innate immune suppression in the tumor
      microenvironment. In tumor cells, BGB324 treatment drove epithelial
      differentiation, expression of nucleoside transporters affecting gemcitabine
      response, and an immune stimulatory microenvironment. Our results establish a
      preclinical mechanistic rationale for the clinical development of Axl inhibitors
      to improve the treatment of PDAC patients.Significance: These results establish a
      preclinical mechanistic rationale for the clinical development of AXL inhibitors
      to improve the treatment of PDAC patients. Cancer Res; 78(1); 246-55. (c)2017
      AACR.

PMID- 29180469
TI  - SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation.
AB  - The mitochondrial serine hydroxymethyltransferase SHMT2, which catalyzes the rate
      limiting step in serine catabolism, drives cancer cell proliferation, but how
      this role is regulated is undefined. Here, we report that the sirtuin SIRT5
      desuccinylates SHMT2 to increase its activity and drive serine catabolism in
      tumor cells. SIRT5 interaction directly mediated desuccinylation of lysine 280 on
      SHMT2, which was crucial for activating its enzymatic activity. Conversely,
      hypersuccinylation of SHMT2 at lysine 280 was sufficient to inhibit its enzymatic
      activity and downregulate tumor cell growth in vitro and in vivo Notably, SIRT5
      inactivation led to SHMT2 enzymatic downregulation and to abrogated cell growth
      under metabolic stress. Our results reveal that SHMT2 desuccinylation is a
      pivotal signal in cancer cells to adapt serine metabolic processes for rapid
      growth, and they highlight SIRT5 as a candidate target for suppressing serine
      catabolism as a strategy to block tumor growth.Significance: These findings
      reveal a novel mechanism for controlling cancer cell proliferation by blocking
      serine catabolism, as a general strategy to impede tumor growth. Cancer Res;
      78(2); 372-86. (c)2017 AACR.

PMID- 29180470
TI  - ERalpha Binding by Transcription Factors NFIB and YBX1 Enables FGFR2 Signaling to
      Modulate Estrogen Responsiveness in Breast Cancer.
AB  - Two opposing clusters of transcription factors (TF) have been associated with the
      differential risks of estrogen receptor positive or negative breast cancers, but
      the mechanisms underlying the opposing functions of the two clusters are
      undefined. In this study, we identified NFIB and YBX1 as novel interactors of the
      estrogen receptor (ESR1). NFIB and YBX1 are both risk TF associated with
      progression of ESR1-negative disease. Notably, they both interacted with the ESR1
      FOXA1 complex and inhibited the transactivational potential of ESR1. Moreover,
      signaling through FGFR2, a known risk factor in breast cancer development,
      augmented these interactions and further repressed ESR1 target gene expression.
      We therefore show that members of two opposing clusters of risk TFs associated
      with ESR1-positive and -negative breast cancer can physically interact. We
      postulate that this interaction forms a toggle between two developmental pathways
      affected by FGFR2 signaling, possibly offering a junction to exploit
      therapeutically.Significance: Binding of the transcription factors NFIB and YBX1
      to the estrogen receptor can promote an estrogen-independent phenotype that can
      be reverted by inhibiting FGFR2 signaling. Cancer Res; 78(2); 410-21. (c)2017
      AACR.

PMID- 29180471
TI  - MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21
      Levels.
AB  - The MYC oncogene broadly promotes transcription mediated by all nuclear RNA
      polymerases, thereby acting as a positive modifier of global gene expression.
      Here, we report that MYC stimulates the transcription of DANCR, a long noncoding
      RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR
      through its overexpression in a transgenic model of MYC-induced lymphoma, but
      found that it was broadly upregulated in many human cancer cell lines and
      cancers, including most notably in prostate and ovarian cancers. Mechanistic
      investigations indicated that DANCR limited the expression of cell-cycle
      inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell
      proliferation could be partially rescued by p21 silencing. In a xenograft model
      of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR
      in vivo was sufficient to strongly inhibit tumor growth. Our observations expand
      knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a
      critical lncRNA widely overexpressed in human cancers.Significance: These
      findings expand knowledge of how MYC drives cancer cell proliferation by
      identifying an oncogenic long noncoding RNA that is widely overexpressed in human
      cancers. Cancer Res; 78(1); 64-74. (c)2017 AACR.

PMID- 29180472
TI  - Utility of Single-Cell Genomics in Diagnostic Evaluation of Prostate Cancer.
AB  - A distinction between indolent and aggressive disease is a major challenge in
      diagnostics of prostate cancer. As genetic heterogeneity and complexity may
      influence clinical outcome, we have initiated studies on single tumor cell
      genomics. In this study, we demonstrate that sparse DNA sequencing of single-cell
      nuclei from prostate core biopsies is a rich source of quantitative parameters
      for evaluating neoplastic growth and aggressiveness. These include the presence
      of clonal populations, the phylogenetic structure of those populations, the
      degree of the complexity of copy-number changes in those populations, and
      measures of the proportion of cells with clonal copy-number signatures. The
      parameters all showed good correlation to the measure of prostatic malignancy,
      the Gleason score, derived from individual prostate biopsy tissue cores.
      Remarkably, a more accurate histopathologic measure of malignancy, the surgical
      Gleason score, agrees better with these genomic parameters of diagnostic biopsy
      than it does with the diagnostic Gleason score and related measures of diagnostic
      histopathology. This is highly relevant because primary treatment decisions are
      dependent upon the biopsy and not the surgical specimen. Thus, single-cell
      analysis has the potential to augment traditional core histopathology, improving
      both the objectivity and accuracy of risk assessment and inform treatment
      decisions.Significance: Genomic analysis of multiple individual cells harvested
      from prostate biopsies provides an indepth view of cell populations comprising a
      prostate neoplasm, yielding novel genomic measures with the potential to improve
      the accuracy of diagnosis and prognosis in prostate cancer. Cancer Res; 78(2);
      348-58. (c)2017 AACR.

PMID- 29180473
TI  - New Mechanisms of Resistance to MEK Inhibitors in Melanoma Revealed by Intravital
      Imaging.
AB  - Targeted therapeutics that are initially effective in cancer patients nearly
      invariably engender resistance at some stage, an inherent challenge in the use of
      any molecular-targeted drug in cancer settings. In this study, we evaluated
      resistance mechanisms arising in metastatic melanoma to MAPK pathway kinase
      inhibitors as a strategy to identify candidate strategies to limit risks of
      resistance. To investigate longitudinal responses, we developed an intravital
      serial imaging approach that can directly visualize drug response in an inducible
      RAF-driven, autochthonous murine model of melanoma incorporating a fluorescent
      reporter allele (tdTomatoLSL). Using this system, we visualized formation and
      progression of tumors in situ, starting from the single-cell level longitudinally
      over time. Reliable reporting of the status of primary murine tumors treated with
      the selective MEK1/2 inhibitor (MEKi) trametinib illustrated a time-course of
      initial drug response and persistence, followed by the development of drug
      resistance. We found that tumor cells adjacent to bundled collagen had a
      preferential persistence in response to MEKi. Unbiased transcriptional and kinome
      reprogramming analyses from selected treatment time points suggested increased c
      Kit and PI3K/AKT pathway activation in resistant tumors, along with enhanced
      expression of epithelial genes and epithelial-mesenchymal transition
      downregulation signatures with development of MEKi resistance. Similar trends
      were observed following simultaneous treatment with BRAF and MEK inhibitors
      aligned to standard-of-care combination therapy, suggesting these reprogramming
      events were not specific to MEKi alone. Overall, our results illuminate the
      integration of tumor-stroma dynamics with tissue plasticity in melanoma
      progression and provide new insights into the basis for drug response,
      persistence, and resistance.Significance: A longitudinal study tracks the course
      of MEKi treatment in an autochthonous imageable murine model of melanoma from
      initial response to therapeutic resistance, offering new insights into the basis
      for drug response, persistence, and resistance. Cancer Res; 78(2); 542-57.
      (c)2017 AACR.

PMID- 29180474
TI  - Vitamin C Sensitizes Melanoma to BET Inhibitors.
AB  - Bromodomain and extraterminal inhibitors (BETi) are promising cancer therapies,
      yet prominent side effects of BETi at effective doses have been reported in phase
      I clinical trials. Here, we screened a panel of small molecules targeting
      epigenetic modulators against human metastatic melanoma cells. Cells were
      pretreated with or without ascorbate (vitamin C), which promotes DNA
      demethylation and subsequently changes the sensitivity to drugs. Top hits were
      structurally unrelated BETi, including JQ1, I-BET151, CPI-203, and BI-2536.
      Ascorbate enhanced the efficacy of BETi by decreasing acetylation of histone H4,
      but not H3, while exerting no effect on the expression of BRD proteins. Histone
      acetyltransferase 1 (HAT1), which catalyzes H4K5ac and H4K12ac, was downregulated
      by ascorbate mainly via the TET-mediated DNA hydroxymethylation pathway. Loss of
      H4ac, especially H4K5ac and H4K12ac, disrupted the interaction between BRD4 and
      H4 by which ascorbate and BETi blocked the binding of BRD4 to acetylated
      histones. Cotreatment with ascorbate and JQ1 induced apoptosis and inhibited
      proliferation of cultured melanoma cells. Ascorbate deficiency as modeled in Gulo
      /- mice diminished the treatment outcome of JQ1 for melanoma tumorgraft. In
      contrast, ascorbate supplementation lowered the effective dose of JQ1 needed to
      successfully inhibit melanoma tumors in mice. On the basis of our findings,
      future clinical trials with BETi should consider ascorbate levels in patients.
      Furthermore, ascorbate supplementation might help reduce the severe side effects
      that arise from BETi therapy by reducing the dosage necessary for
      treatment.Significance: This study shows that ascorbate can enhance the efficacy
      of BET inhibitors, providing a possible clinical solution to challenges arising
      in phase I trials from the dose-dependent side effects of this class of
      epigenetic therapy. Cancer Res; 78(2); 572-83. (c)2017 AACR.

PMID- 29180475
TI  - Distinct TP63 Isoform-Driven Transcriptional Signatures Predict Tumor Progression
      and Clinical Outcomes.
AB  - TP63 is required to maintain stem cell pluripotency and suppresses the metastatic
      potential of cancer cells through multiple mechanisms. These functions are
      differentially regulated by individual isoforms, necessitating a deeper
      understanding of how the distinct transcriptional programs controlled by these
      isoforms affect cancer progression and outcomes. In this study, we conducted a
      pan-cancer analysis of The Cancer Genome Atlas to identify transcriptional
      networks regulated by TAp63 and DeltaNp63 using transcriptomes derived from
      epidermal cells of TAp63-/- and DeltaNp63-/- mice. Analysis of 17 cancer
      developmental and 27 cancer progression signatures revealed a consistent tumor
      suppressive pattern for TAp63. In contrast, we identified pleiotropic roles for
      DeltaNp63 in tumor development and found that its regulation of Lef1 was crucial
      for its oncogenic role. DeltaNp63 performed a distinctive role as suppressor of
      tumor progression by cooperating with TAp63 to modulate key biological pathways,
      principally cell-cycle regulation, extracellular matrix remodeling, epithelial-to
      mesenchymal transition, and the enrichment of pluripotent stem cells.
      Importantly, these TAp63 and DeltaNp63 signatures prognosticated progression and
      survival, even within specific stages, in bladder and renal carcinomas as well as
      low-grade gliomas. These data describe a novel approach for understanding
      transcriptional activities of TP63 isoforms across a large number of cancer
      types, potentially enabling identification of patient subsets most likely to
      benefit from therapies predicated on manipulating specific TP63
      isoforms.Significance: Transcriptomic analyses of patient samples and murine
      knockout models highlight the prognostic role of several critical mechanisms of
      tumor suppression that are regulated by TP63. Cancer Res; 78(2); 451-62. (c)2017
      AACR.

PMID- 29180476
TI  - A Potent, Metabolically Stable Tubulin Inhibitor Targets the Colchicine Binding
      Site and Overcomes Taxane Resistance.
AB  - Antimitotics that target tubulin are among the most useful chemotherapeutic
      drugs, but their clinical activity is often limited by the development of
      multidrug resistance. We recently discovered the novel small-molecule DJ101 as a
      potent and metabolically stable tubulin inhibitor that can circumvent the drug
      efflux pumps responsible for multidrug resistance of existing tubulin inhibitors.
      In this study, we determined the mechanism of action of this drug. The basis for
      its activity was illuminated by solving the crystal structure of DJ101 in complex
      with tubulin at a resolution of 2.8A. Investigations of the potency of DJ101 in a
      panel of human metastatic melanoma cell lines harboring major clinically relevant
      mutations defined IC50 values of 7-10 nmol/L. In cells, DJ101 disrupted
      microtubule networks, suppressed anchorage-dependent melanoma colony formation,
      and impaired cancer cell migration. In melanoma-bearing mice, DJ101
      administration inhibited tumor growth and reduced lung metastasis in the absence
      of observable toxicity. DJ101 also completely inhibited tumor growth in a
      paclitaxel-resistant xenograft mouse model of human prostate cancer (PC-3/TxR),
      where paclitaxel was minimally effective. Our findings offer preclinical proof of
      concept for the continued development of DJ101 as a next-generation tubulin
      inhibitor for cancer therapy.Significance: These findings offer preclinical proof
      of concept for the continued development of DJ101 as a next-generation
      antitubulin drug for cancer therapy. Cancer Res; 78(1); 265-77. (c)2017 AACR.

PMID- 29180477
TI  - miR-139-5p Modulates Radiotherapy Resistance in Breast Cancer by Repressing
      Multiple Gene Networks of DNA Repair and ROS Defense.
AB  - Radiotherapy is essential to the treatment of most solid tumors and acquired or
      innate resistance to this therapeutic modality is a major clinical problem. Here
      we show that miR-139-5p is a potent modulator of radiotherapy response in breast
      cancer via its regulation of genes involved in multiple DNA repair and reactive
      oxygen species defense pathways. Treatment of breast cancer cells with a miR-139
      5p mimic strongly synergized with radiation both in vitro and in vivo, resulting
      in significantly increased oxidative stress, accumulation of unrepaired DNA
      damage, and induction of apoptosis. Several miR-139-5p target genes were also
      strongly predictive of outcome in radiotherapy-treated patients across multiple
      independent breast cancer cohorts. These prognostically relevant miR-139-5p
      target genes were used as companion biomarkers to identify radioresistant breast
      cancer xenografts highly amenable to sensitization by cotreatment with a miR-139
      5p mimetic.Significance: The microRNA described in this study offers a
      potentially useful predictive biomarker of radiosensitivity in solid tumors and a
      generally applicable druggable target for tumor radiosensitization. Cancer Res;
      78(2); 501-15. (c)2017 AACR.

PMID- 29180478
TI  - Perioperative, Spatiotemporally Coordinated Activation of T and NK Cells Prevents
      Recurrence of Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating
      cancer resistant to therapy, including checkpoint immunotherapies, and early
      tumor resection and (neo)adjuvant chemotherapy fails to improve a poor prognosis.
      In a transgenic mouse model of resectable PDAC, we investigated the coordinated
      activation of T and natural killier (NK) cells in addition to gemcitabine
      chemotherapy to prevent tumor recurrence. Only neoadjuvant, but not adjuvant
      treatment with a PD-1 antagonist effectively supported chemotherapy and
      suppressed local tumor recurrence and improved survival involving both NK and T
      cells. Local T-cell activation was confirmed by increased tumor infiltration with
      CD103+CD8+ T cells and neoantigen-specific CD8 T lymphocytes against the marker
      neoepitope LAMA4-G1254V. To achieve effective prevention of distant metastases in
      a complementary approach, we blocked the NK-cell checkpoint CD96, an inhibitory
      NK-cell receptor that binds CD155, which was abundantly expressed in primary PDAC
      and metastases of human patients. In gemcitabine-treated mice, neoadjuvant PD-1
      blockade followed by adjuvant inhibition of CD96 significantly prevented relapse
      of PDAC, allowing for long-term survival. In summary, our results show in an
      aggressively growing transgenic mouse model of PDAC that the coordinated
      activation of both innate and adaptive immunity can effectively reduce the risk
      of tumor recurrence after surgery, facilitating long-term remission of this
      lethal disease.Significance: Coordinated neoadjuvant and adjuvant immunotherapies
      reduce the risk of disease relapse after resection of murine PDAC, suggesting
      this concept for future clinical trials. Cancer Res; 78(2); 475-88. (c)2017 AACR.

PMID- 29180479
TI  - Influence of residual force enhancement and elongation of attached cross-bridges
      on stretch-shortening cycle in skinned muscle fibers.
AB  - Increased muscle force during stretch-shortening cycles (SSCs) has been widely
      examined. However, the mechanisms causing increased muscle force in SSCs remain
      unknown. The purpose of this study was to determine the influence of residual
      force enhancement and elongation of attached cross-bridges on the work
      enhancement in SSCs. For the Control condition, skinned rabbit soleus fibers were
      elongated passively from an average sarcomere length of 2.4 to 3.0 MUm, activated
      and then actively shortened to 2.4 MUm. For the Transition condition, fibers were
      elongated actively from an average sarcomere length of 2.4 to 3.0 MUm. Two
      seconds after the end of active lengthening, fibers were actively shortened to
      2.4 MUm. In the SSC condition, fibers were lengthened actively from an average
      sarcomere length of 2.4 to 3.0 MUm, and then immediately shortened actively to
      2.4 MUm. Increased muscle force in the SSCs was quantified by the increase in
      mechanical work during active shortening compared to the mechanical work measured
      during the purely active shortening contractions. Work enhancement was
      significantly greater in the SSC compared to the Transition conditions. This
      difference was associated with the pause given between the active lengthening and
      shortening phase in the Transition test, which likely resulted in a reduction of
      the average elongation of the attached cross-bridges caused by active stretching.
      Since some work enhancement was still observed in the Transition condition,
      another factor, for example the stretch-induced residual force enhancement, must
      also have contributed to the work enhancement in SSCs.

PMID- 29180480
TI  - Motor module activation sequence and topography in the spinal cord during air
      stepping in human: Insights into the traveling wave in spinal locomotor circuits.
AB  - Coordinated locomotor muscle activity is generated by the spinal central pattern
      generators (CPGs), which are modulated by peripheral and supraspinal inputs. The
      CPGs would consist of multiple motor modules generating basic muscle activity,
      which are distributed rostrocaudally along the spinal cord. To activate the motor
      modules in proper sequence, rostrocaudally traveling waves of activation in the
      spinal cord are important mechanisms in the CPGs. The traveling waves of
      activation have been observed in nonhuman vertebrates. However, they have not yet
      been confirmed during human locomotion. Although, rostrocaudal wave-like
      activations in the spinal cord were observed during walking in humans in a
      previous study, the propagation shifted rostrally toward the upper lumbar
      segments at foot contact. Here, using an air stepping task to remove the foot
      contact interactions, we examined whether the traveling wave mechanism exists in
      the human spinal circuits based on the activation sequence of motor modules and
      their topography. We measured electromyographic activity of lower leg muscles
      during the air-stepping task. Then, we extracted motor modules (i.e., basic
      patterns of sets of muscle activations: muscle synergies) from the measured
      muscle activities using nonnegative matrix factorization method. Next, we
      reconstructed motoneuron (MN) activity from each module activity based on
      myotomal charts. We identified four types of motor modules from muscle activities
      during the air-stepping task. Each motor module represented different sets of
      synergistic muscle activations. MN clusters innervating each motor module were
      sequentially activated from the rostral to caudal region in the spinal cord, from
      the initial flexion to the last extension phase during air-stepping. The
      rostrocaudally sequential activation of MN clusters suggests the possibility that
      rostrocaudally traveling waves exist in human locomotor spinal circuits. The
      present results advance the understanding of human locomotor control mechanisms,
      and provide important insights into the evolution of locomotor networks in
      vertebrates.

PMID- 29180481
TI  - Validity and variability of xBRS: instantaneous cardiac baroreflex sensitivity.
AB  - Spontaneous oscillations of blood pressure (BP) and interbeat interval (IBI) may
      reveal important information on the underlying baroreflex control and regulation
      of BP We evaluated the method of continuously measured instantaneous baroreflex
      sensitivity by cross correlation (xBRS) validating its mean value against the
      gold standard of phenylephrine (Phe) and nitroprusside (SNP) bolus injections,
      and focusing on its spontaneous changes quantified as variability around the
      mean. For this purpose, we analyzed data from an earlier study of eight healthy
      males (aged 25-46 years) who had received Phe and SNP in conditions of baseline
      and autonomic blocking agents: atropine, propranolol, and clonidine. Average xBRS
      corresponds well to Phe/SNP-BRS, with xBRS levels ranging from 1.2 (atropine) to
      102 msec/mmHg (subject asleep under clonidine). Time shifts from BP- to IBI
      signal increased from <=1 sec (maximum correlations within the current heartbeat)
      to 3-5 sec (under atropine). Plotted on a logarithmic vertical scale, xBRS values
      show 40% variability (defined as SD/mean) over the whole range in the various
      conditions, except twice when the subjects had fallen asleep and it dropped to
      20%. The xBRS oscillates at frequencies of 0.1 Hz and lower, dominant between
      0.02-0.05 Hz. Although xBRS is the result of IBI/BP-changes, no linear coherence
      was found in the cross-spectra of the xBRS-signal and IBI or BP We speculate that
      the level of variability in the xBRS-signal may act as a probe into the central
      nervous condition, as evidenced in the two subjects who fell asleep with high
      xBRS and only 20% of relative variation.

PMID- 29180483
TI  - Decoding spatial attention with EEG and virtual acoustic space.
AB  - Decoding spatial attention based on brain signals has wide applications in brain
      computer interface (BCI). Previous BCI systems mostly relied on visual patterns
      or auditory stimulation (e.g., loudspeakers) to evoke synchronous brain signals.
      There would be difficulties to cover a large range of spatial locations with such
      a stimulation protocol. The present study explored the possibility of using
      virtual acoustic space and a visual-auditory matching paradigm to overcome this
      issue. The technique has the flexibility of generating sound stimulation from
      virtually any spatial location. Brain signals of eight human subjects were
      obtained with a 32-channel Electroencephalogram (EEG). Two amplitude-modulated
      noise or speech sentences carrying distinct spatial information were presented
      concurrently. Each sound source was tagged with a unique modulation phase so that
      the phase of the recorded EEG signals indicated the sound being attended to. The
      phase-tagged sound was further filtered with head-related transfer functions to
      create the sense of virtual space. Subjects were required to pay attention to the
      sound source that best matched the location of a visual target. For all the
      subjects, the phase of a single sound could be accurately reflected over the
      majority of electrodes based on EEG responses of 90 s or less. The electrodes
      providing significant decoding performance on auditory attention were fewer and
      may require longer EEG responses. The reliability and efficiency of decoding with
      a single electrode varied with subjects. Overall, the virtual acoustic space
      protocol has the potential of being used in practical BCI systems.

PMID- 29180484
TI  - Repeated bouts of resistance exercise with short recovery periods activates mTOR
      signaling, but not protein synthesis, in mouse skeletal muscle.
AB  - The recovery period between bouts of exercise is one of the major factors
      influencing the effects of resistance exercise, in addition to exercise intensity
      and volume. However, the effects of shortening the recovery time between bouts of
      resistance exercise on subsequent protein synthesis remain unclear. In this
      study, we investigated the consequences of shortening the recovery time between
      bouts of resistance exercise on protein synthesis and related processes in mouse
      skeletal muscles. Eighteen male C57BL/6J mice were randomly subjected to three
      bouts of resistance exercise with 72 (72H), 24 (24H), or 8 h (8H) of recovery
      periods between bouts. Resistance exercise, consisting of five sets of 3 s * 10
      isometric contractions with 3 min rest between sets, was elicited on the right
      tibialis anterior muscle via percutaneous electrical stimulation on the deep
      peroneal nerve under isoflurane anesthesia. The left muscle served as an internal
      control. Six hours after the third bout of exercise, protein synthesis was found
      to be activated in the 72H and 24H groups, but not in the 8H group.
      Phosphorylation of p70S6K at Thr 389, a marker of mammalian target of rapamycin
      (mTOR) signaling, was increased in all groups, with the 8H group showing the
      highest magnitude. In contrast, protein carbonylation was observed only in mice
      in the 8H group. These results suggest that repeated bouts of resistance exercise
      with 8 h of recovery periods do not effectively increase the levels of muscle
      protein synthesis despite activation of the mTOR signaling pathway, which likely
      involves oxidative stress.

PMID- 29180482
TI  - Deep-targeted sequencing of endothelial nitric oxide synthase gene exons uncovers
      exercise intensity and ethnicity-dependent associations with post-exercise
      hypotension.
AB  - In previous studies, we found an endothelial nitric oxide synthase gene (NOS3)
      variant rs2070744 associated with the ambulatory blood pressure (BP) response
      following bouts of moderate and vigorous intensity acute exercise, termed post
      exercise hypotension (PEH). In a validation cohort, we sequenced NOS3 exons for
      associations with PEH Obese (30.9 +/- 3.6 kg.m-2) African American (n = 14) [AF]
      and Caucasian (n = 9) adults 42.0 +/- 9.8 years with hypertension (139.8 +/-
      10.4/84.6 +/- 6.2 mmHg) performed three random experiments: bouts of vigorous and
      moderate intensity cycling and control. Subjects were attached to an ambulatory
      BP monitor for 19 h. We performed deep-targeted exon sequencing with the Illumina
      TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor
      alleles (#MA) and selected for additional statistical analysis based upon
      Bonferonni or Benjamini-Yekutieli multiple testing-corrected P-values under time
      adjusted linear models for 19 hourly BP measurements for each subject. After
      vigorous intensity over 19 h, among NOS3 variants passing multiple testing
      thresholds, as the #MA increased in rs891512 (P = 6.4E-04), rs867225 (P = 6.5E
      04), rs743507 (P = 2.6E-06), and rs41483644 (P = 2.4E-04), systolic (SBP)
      decreased from 17.5 to 33.7 mmHg; and in rs891512 (P = 9.7E-05), rs867225 (P =
      2.6E-05), rs41483644 (P = 1.6E-03), rs3730009 (P = 2.6E-04), and rs77325852 (P =
      5.6E-04), diastolic BP decreased from 11.1 mmHg to 20.3 mmHg among AF only. In
      contrast, after moderate intensity over 19 h in NOS3 rs3918164, as the #MA
      increased, SBP increased by 16.6 mmHg (P = 2.4E-04) among AF only. NOS3 variants
      exhibited associations with PEH after vigorous, but not moderate intensity
      exercise among AF only. NOS3 should be studied further for its effects on PEH in
      a large, ethnically diverse sample of adults with hypertension to confirm our
      findings.

PMID- 29180485
TI  - Validation of whole room indirect calorimeters: refinement of current
      methodologies.
AB  - Whole room indirect calorimeter (WRIC) validation techniques consist of propane
      combustion (PC) or infusion of mixed carbon dioxide (CO2) and nitrogen (N2) by a
      precision blender (PB). To determine the best method, PC of 6, 10, 22-h and PB
      infusions of 6, 10, and 14-h, were conducted. The 14-h infusion consisted of two
      metabolic settings. Energy expenditure (EE; kJ), ventilation (V; liters/min) of
      oxygen (VO2), VCO2, and respiratory quotient (VCO2/VO2) obtained from the WRIC
      were extrapolated to the respective test durations and compared to similarly
      calculated values. Moreover, accurate equations (AE) were derived to correct
      infusions for additional N2 As a final evaluation of a PC validated WRIC, weight
      maintenance (WM), energy balance (EB), respiratory quotient (RQ), and food
      quotients (FQ) were determined in 22 subjects who had repeat 24-h EE
      measurements. Statistical analyses (P < 0.05) were conducted (SPSS, version 23).
      Significant differences in RQ existed between PC and stoichiometry after 6-h.
      Errors for the rest of the PC tests ranged from -1.5 +/- 2.4 (VCO2) to 2.8 +/-
      4.6% (EE). When compared with the WRIC, all uncorrected metabolic parameters for
      six and 10-h PB infusions were significantly different with errors from -12.8 +/-
      1.6 (VO2) to 6.0 +/- 2.8% (RQ). The AE reduced the magnitude of errors to -12.4
      +/- 1.5 (RQ) to 2.2 +/- 3.0% (RQ). The PB infusion with two settings showed
      similar performance. No differences in WM, EB, RQ, or FQ existed in the subjects.
      In conclusion, 10-h PC tests are sufficient for validating WRICs.

PMID- 29180488
TI  - Rhesus Macaque Myeloid-Derived Suppressor Cells Demonstrate T Cell Inhibitory
      Functions and Are Transiently Increased after Vaccination.
AB  - Myeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses
      in several pathological conditions. Whether MDSCs increase and influence T cell
      responses in temporary inflammation, such as after vaccine administration, is
      unknown. Using the rhesus macaque model, which is critical for late-stage vaccine
      testing, we demonstrate that monocytic (M)-MDSCs and polymorphonuclear (PMN)
      MDSCs can be detected using several of the markers used in humans. However,
      whereas rhesus M-MDSCs lacked expression of CD33, PMN-MDSCs were identified as
      CD33+ low-density neutrophils. Importantly, both M-MDSCs and PMN-MDSCs showed
      suppression of T cell proliferation in vitro. The frequency of circulating MDSCs
      rapidly and transiently increased 24 h after vaccine administration. M-MDSCs
      infiltrated the vaccine injection site, but not vaccine-draining lymph nodes.
      This was accompanied by upregulation of genes relevant to MDSCs such as arginase
      1, IDO1, PDL1, and IL-10 at the injection site. MDSCs may therefore play a role
      in locally maintaining immune balance during vaccine-induced inflammation.

PMID- 29180486
TI  - The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression
      Kinetics with Atypical RNASEL Induction.
AB  - Bats host a large number of zoonotic viruses, including several viruses that are
      highly pathogenic to other mammals. The mechanisms underlying this rich viral
      diversity are unknown, but they may be linked to unique immunological features
      that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to
      viral infection by inducing IFNs, which trigger antiviral defenses through IFN
      stimulated gene (ISG) expression. Although the IFN system of several bats is
      characterized at the genomic level, less is known about bat IFN-mediated
      transcriptional responses. In this article, we show that IFN signaling in bat
      cells from the black flying fox (Pteropus alecto) consists of conserved and
      unique ISG expression profiles. In IFN-stimulated cells, bat ISGs comprise two
      unique temporal subclusters with similar early induction kinetics but distinct
      late-phase declines. In contrast, human ISGs lack this decline phase and remained
      elevated for longer periods. Notably, in unstimulated cells, bat ISGs were
      expressed more highly than their human counterparts. We also found that the
      antiviral effector 2-5A-dependent endoribonuclease, which is not an ISG in
      humans, is highly IFN inducible in black flying fox cells and contributes to cell
      intrinsic control of viral infection. These studies reveal distinctive innate
      immune features that may underlie a unique virus-host relationship in bats.

PMID- 29180487
TI  - Toxoplasma gondii Inactivates Human Plasmacytoid Dendritic Cells by Functional
      Mimicry of IL-10.
AB  - Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-alpha, an
      antiviral cytokine involved in immunomodulation and control of HIV type 1
      replication, whereas Toxoplasma gondii is a life-threatening opportunistic
      infection in AIDS patients. During infection with HIV type 1, human pDCs decrease
      in circulation and remaining pDC produce lower amounts of IFN-alpha in response
      to viral stimulation. In this study, we investigated the impact of coinfection
      with T. gondii on the innate virus-directed responses of human pDCs. Using
      intracellular flow cytometry and fluorescence microscopy, we determined that T.
      gondii invaded but did not induce IFN-alpha or TNF-alpha in human pDC. However,
      T. gondii inhibited IFN-alpha and TNF-alpha produced in response to HSV and HIV,
      thus functionally inactivating pDC. IFN-alpha production was inhibited only in
      cells infected by T. gondii, which inhibited neither uptake of GFP-HSV nor
      localization of TLR9 in CD71+ endosomes, directing us to investigate downstream
      events. Using imaging flow cytometry, we found that both T. gondii and IL-10
      inhibited virus-induced nuclear translocation, but not phosphorylation, of IFN
      response factor 7. Blockade of IFN response factor 7 nuclear translocation and
      inhibition of the IFN-alpha response was partially reversed by a deficiency in
      the T. gondii-derived ROP16 kinase, known to directly phosphorylate STAT3, a
      critical mediator of IL-10's anti-inflammatory effects. Taken together, our
      results indicate that T. gondii suppresses pDC activation by mimicking IL-10's
      regulatory effects through an ROP16 kinase-dependent mechanism. Our findings
      further imply a convergent mechanism of inhibition of TLR signaling by T. gondii
      and IL-10 and suggest potential negative consequences of HIV/T. gondii
      coinfection.

PMID- 29180489
TI  - Downregulation of NFAT3 Due to Lack of T-Box Transcription Factor TBX5 Is Crucial
      for Cytokine Expression in T Cells.
AB  - The NFAT family transcription factors play crucial roles in immunological and
      other biological activities. NFAT3 is rarely expressed in T cells, and the
      mechanisms and significance of the specific NFAT3 downregulation in T cells have
      been unknown. In human CD4+ T cells, overexpression of NFAT1 and NFAT3 enhanced
      and suppressed IL-2 expression, respectively. NFAT3 downregulation in Jurkat
      cells using RNA interference technology augmented IL-2 expression, whereas a
      knockdown of NFAT1, NFAT2, and NFAT4 suppressed it. The promoter/enhancer
      activity of the NFAT-binding site in the IL-2 gene was upregulated and
      downregulated by NFAT1 and NFAT3, respectively. A study employing NFAT1/NFAT3
      chimeric molecules revealed that the region in NFAT3 responsible for NFAT
      promoter activity inhibition was located within its N-terminal transactivation
      domain, Ca2+-regulatory domain, and DNA-binding domain. Downregulation of NFAT3
      expression in T cells is mediated by lower chromatin accessibility and enhancer
      activity in its promoter in comparison with aortic smooth muscle cells expressing
      endogenous NFAT3. The binding sites of T-box transcription factor TBX5 and NK-2
      transcription factor-related locus 5 Nkx2.5, which were expressed at higher
      levels in aortic smooth muscle cells than in T cells, were located within the 
      387 to +97 NFAT3 promoter region, exhibiting the maximum enhancer activity.
      Mutating the binding site of TBX5 but not Nkx2.5 diminished the NFAT3 promoter
      activity, whereas the overexpression of TBX5 enhanced it. Introduction of TBX5
      into CD4+ T cells enhanced the expression of NFAT3 and suppressed that of IL-2.
      TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine
      producing activity of T cells.

PMID- 29180490
TI  - Identity and Diversity of Human Peripheral Th and T Regulatory Cells Defined by
      Single-Cell Mass Cytometry.
AB  - Human CD3+CD4+ Th cells, FOXP3+ T regulatory (Treg) cells, and T regulatory type
      1 (Tr1) cells are essential for ensuring peripheral immune response and
      tolerance, but the diversity of Th, Treg, and Tr1 cell subsets has not been fully
      characterized. Independent functional characterization of human Th1, Th2, Th17, T
      follicular helper (Tfh), Treg, and Tr1 cells has helped to define unique surface
      molecules, transcription factors, and signaling profiles for each subset.
      However, the adequacy of these markers to recapitulate the whole CD3+CD4+ T cell
      compartment remains questionable. In this study, we examined CD3+CD4+ T cell
      populations by single-cell mass cytometry. We characterize the CD3+CD4+ Th, Treg,
      and Tr1 cell populations simultaneously across 23 memory T cell-associated
      surface and intracellular molecules. High-dimensional analysis identified several
      new subsets, in addition to the already defined CD3+CD4+ Th, Treg, and Tr1 cell
      populations, for a total of 11 Th cell, 4 Treg, and 1 Tr1 cell subsets. Some of
      these subsets share markers previously thought to be selective for Treg, Th1,
      Th2, Th17, and Tfh cells, including CD194 (CCR4)+FOXP3+ Treg and CD183 (CXCR3)+T
      bet+ Th17 cell subsets. Unsupervised clustering displayed a phenotypic
      organization of CD3+CD4+ T cells that confirmed their diversity but showed
      interrelation between the different subsets, including similarity between Th1-Th2
      Tfh cell populations and Th17 cells, as well as similarity of Th2 cells with Treg
      cells. In conclusion, the use of single-cell mass cytometry provides a systems
      level characterization of CD3+CD4+ T cells in healthy human blood, which
      represents an important baseline reference to investigate abnormalities of
      different subsets in immune-mediated pathologies.

PMID- 29180491
TI  - Are Meta-Analyses a Form of Medical Fake News? Thoughts About How They Should
      Contribute to Medical Science and Practice.

PMID- 29180492
TI  - Mild Thyroid Dysfunction: A Potential Target in Prevention of Atrial
      Fibrillation?

PMID- 29180493
TI  - Is Less Really More? Conscious Sedation or General Anesthesia for Transcatheter
      Aortic Valve Replacement.

PMID- 29180494
TI  - Metabolism: A Direct Link Between Cardiac Structure and Function.

PMID- 29180496
TI  - Highlights From the Circulation Family of Journals.

PMID- 29180497
TI  - Impact of Coronary Computed Tomography Angiography Findings on Initiation of
      Cardioprotective Medications.

PMID- 29180495
TI  - Handheld Echocardiography: Current State and Future Perspectives.
AB  - Echocardiography is the primary imaging modality for diagnosing cardiac
      conditions. Over the past 2 decades, technological advancements have resulted in
      the emergence of miniaturized handheld ultrasound equipment that is compact and
      battery operated, and handheld echocardiography can be readily performed at the
      point of care with reasonable image quality. The simplicity of use, availability
      at the patient's bedside, easy transportability, and relatively low cost have
      encouraged physicians to use these devices for prompt medical decision making. As
      a consequence, the use of handheld echocardiography is on the rise even among
      nonechocardiographers (intensivists, emergency care physicians, internists, and
      medical students). One of the real utilities of ultrasound-augmented clinical
      diagnosis is in evaluating patients efficiently and selecting patients for
      appropriate downstream diagnostic testing including comprehensive
      echocardiography. Although clinical evidence supports the use of handheld devices
      in various clinical settings and by different users, proficiency in point-of-care
      ultrasound requires dedicated training in both performance and interpretation.
      This review summarizes the existing literature on the use of handheld
      echocardiography in conducting focused cardiac examinations: its training
      requirements, challenges, opportunities, and future perspectives in the care of
      the cardiovascular patient.

PMID- 29180498
TI  - Letter by Campbell Regarding Article, "gammadelta T Cells Mediate Angiotensin II
      Induced Hypertension and Vascular Injury".

PMID- 29180499
TI  - Response by Caillon et al to Letter Regarding Article, "gammadelta T Cells
      Mediate Angiotensin II-Induced Hypertension and Vascular Injury".

PMID- 29180500
TI  - Letter by Jin-shan and Xue-bin Regarding Article, "Prognostic Value of
      Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain: Insights
      From the PROMISE Trial (Prospective Multicenter Imaging Study for Evaluation of
      Chest Pain)".

PMID- 29180501
TI  - Letter by Braillon Regarding Article, "Polygenic Risk Score Identifies Subgroup
      With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin
      Therapy in the Primary Prevention Setting".

PMID- 29180502
TI  - Photo Quiz: Peripheral Blood Smear in a Ugandan Refugee.

PMID- 29180503
TI  - The Role of Scientific and Medical Societies in Journals ... and More: a Micro
      Comic Strip.

PMID- 29180505
TI  - Closing the Brief Case: Confirmed Positive HIV-1 Serological Screening but
      Undetectable RNA Virus Load in a Pregnant Woman.

PMID- 29180504
TI  - The Brief Case: Confirmed Positive HIV-1 Serologic Screening but Undetectable RNA
      Virus Load in a Pregnant Woman.

PMID- 29180506
TI  - Answer to December 2017 Photo Quiz.

PMID- 29180507
TI  - CEBPA mutational analysis in acute myeloid leukaemia by a laboratory-developed
      next-generation sequencing assay.
AB  - AIM: The presence of biallelic CEBPA mutations is a favourable prognostic feature
      in acute myeloid leukaemia (AML). CEBPA mutations are currently identified
      through conventional capillary sequencing (CCS). With the increasing adoption of
      next-generation sequencing (NGS) platforms, challenges with regard to
      amplification efficiency of CEBPA due to the high GC content may be encountered,
      potentially resulting in suboptimal coverage. Here, the performance of an
      amplicon-based NGS method using a laboratory-developed CEBPA-specific Nextera XT
      (CEBNX) was evaluated. METHODS: Mutational analyses of the CEBPA gene of 137 AML
      bone marrow or peripheral blood retrospective specimens were performed by the
      amplification of the CEBPA gene using the Expand Long Range dNTPack and the
      amplicons processed by CCS and NGS. CEBPA-specific libraries were then
      constructed using the Nextera XT V.2 kit. All FASTQ files were then processed
      with the MiSeq Reporter V.2.6.2.3 using the PCR Amplicon workflow via the
      customised CEBPA-specific manifest file. The variant calling format files were
      analysed using the Illumina Variant Studio V.2.2. RESULTS: A coverage per base of
      3631X to 28184X was achieved. 22 samples (16.1%) were found to contain CEBPA
      mutations, with variant allele frequencies (VAF) ranging from 3.8% to 58.2%.
      Taking CCS as the 'gold standard', sensitivity and specificity of 97% and 97% was
      achieved. For the transactivation domain 2 polymorphism
      (c.584_589dupACCCGC/p.His195_Pro196dup), the CEBNX achieved 100% sensitivity and
      100% specificity relative to CCS. CONCLUSIONS: Our laboratory-developed CEBNX
      workflow shows high coverage and thus overcomes the challenges associated with
      amplification efficiency and low coverage of CEBPA. Therefore, our assay is
      suitable for deployment in the clinical laboratory.

PMID- 29180508
TI  - Incidence and serotype characterisation of Streptococcus agalactiae in a
      Portuguese hospital.
AB  - AIMS: Streptococcus agalactiae, commonly known as group B Streptococcus (GBS),
      has been recognised as a worldwide causative pathogenic agent of neonatal sepsis,
      meningitis and pneumonia. To better understand the behaviour of S. agalactiae in
      pregnant women from a hospital from the North of Portugal, retrospective analyses
      were performed to describe epidemiological, clinical and microbiological
      characteristics of the isolates obtained. METHODS: Based on laboratorial records
      and the hospital's patient files, a 6-year retrospective study was performed to
      analyse S. agalactiae isolates from screened pregnant women between 35 and 37
      weeks of gestation and hospitalised neonates from pregnant women between 24 and
      41 weeks of gestation admitted in Hospital Pedro Hispano. Serotype
      characterisation was also performed in 67 GBS strains. RESULTS: In 6692 pregnant
      women between 35 and 37 weeks of gestation screened between 2011 and 2016, a
      total of 1377 S. agalactiae isolates (21%) were found. A high percentage (40%) of
      unknown colonisation status among hospitalised neonates from pregnant women
      between 24 and 41 weeks of gestations was also found. The incidence of neonatal
      sepsis was 8.7 (95% CI 7.0 to 10.8) cases per 1000 live births. Regarding
      serotype characterisation, serotype III (22.4%) was the most frequent, followed
      by serotype Ia (19.4%) and serotypes Ib and V (both with 17.9%). CONCLUSION: High
      epidemiological values of GBS colonisation and incidence were found in this
      study. In Portugal studies on the epidemiology and behaviour of S. agalactiae
      remain limited, reinforcing the importance and need for S. agalactiae screening
      across the country.

PMID- 29180509
TI  - Subcellular localisation of the stem cell markers OCT4, SOX2, NANOG, KLF4 and c
      MYC in cancer: a review.
AB  - The stem cell markers octamer-binding transcription factor 4, sex-determining
      region Y-box 2, NANOG, Kruppel-like factor 4 and c-MYC are key factors in
      inducing pluripotency in somatic cells, and they have been used to detect cancer
      stem cell subpopulations in a range of cancer types. Recent literature has
      described the subcellular localisation of these markers and their potential
      implications on cellular function. This is a relatively complex and unexplored
      area of research, and the extent of the effect that subcellular localisation has
      on cancer development and growth is largely unknown. This review analyses this
      area of research in the context of the biology of stem cells and cancer and
      explores the potential modulating effect of subcellular localisation of these
      proteins as supported by the literature.

PMID- 29180510
TI  - mRNA Processing Factor CstF-50 and Ubiquitin Escort Factor p97 Are BRCA1/BARD1
      Cofactors Involved in Chromatin Remodeling during the DNA Damage Response.
AB  - The cellular response to DNA damage is an intricate mechanism that involves the
      interplay among several pathways. In this study, we provide evidence of the roles
      of the polyadenylation factor cleavage stimulation factor 50 (CstF-50) and the
      ubiquitin (Ub) escort factor p97 as cofactors of BRCA1/BARD1 E3 Ub ligase,
      facilitating chromatin remodeling during the DNA damage response (DDR). CstF-50
      and p97 formed complexes with BRCA1/BARD1, Ub, and some BRCA1/BARD1 substrates,
      such as RNA polymerase (RNAP) II and histones. Furthermore, CstF-50 and p97 had
      an additive effect on the activation of the ubiquitination of these BRCA1/BARD1
      substrates during DDR. Importantly, as a result of these functional interactions,
      BRCA1/BARD1/CstF-50/p97 had a specific effect on the chromatin structure of genes
      that were differentially expressed. This study provides new insights into the
      roles of RNA processing, BRCA1/BARD1, the Ub pathway, and chromatin structure
      during DDR.

PMID- 29180511
TI  - Functions of the TFIIE-Related Tandem Winged-Helix Domain of Rpc34 in RNA
      Polymerase III Initiation and Elongation.
AB  - Rpc34 is a subunit of the Rpc82/34/31 subcomplex residing on the DNA-binding
      cleft of RNA polymerase (Pol) III. Rpc34 contains a structurally flexible N
      terminal tandem winged-helix (tWH) domain related to the TFIIE transcription
      factor. While the second WH (WH2) fold of the tWH domain is known to function in
      DNA melting activity during transcription initiation, the functional role of the
      WH1 fold is unknown. In this study, we generated a series of new Rpc34 tWH
      mutants conferring a cold-sensitive growth phenotype. We found that the tWH
      mutations severely compromised in vitro transcription activity due to
      destabilization of the preinitiation complex (PIC). Site-specific protein photo
      cross-linking analysis indicated that the tWH domain persistently interacts with
      protein subunits of the Pol III cleft in the PIC and the ternary elongation
      complex (TEC). Furthermore, purified Pol III proteins with tWH mutations also
      showed reduced efficiency in RNA elongation. Our study results suggest that the
      tWH domain is an important protein module above the Pol III cleft that integrates
      protein and nucleic acid interactions for initiation and elongation.

PMID- 29180512
TI  - Junior doctors are being left to run hospital departments unsupervised, GMC
      warns.

PMID- 29180513
TI  - Glucose deprivation induces primary cilium formation through mTORC1 inactivation.
AB  - Primary cilia are antenna-like sensory organelles extending from the surface of
      many cell types that play critical roles in tissue development and homeostasis.
      Here, we examined the effect of nutrient status on primary cilium formation.
      Glucose deprivation significantly increased the number of ciliated cells under
      both serum-fed and -starved conditions. Glucose deprivation-induced ciliogenesis
      was suppressed by overexpression of Rheb, an activator of the mammalian target of
      rapamycin complex-1 (mTORC1). Inactivating mTORC1 by rapamycin treatment or
      Raptor knockdown significantly promoted ciliogenesis. These results indicate that
      glucose deprivation promotes primary cilium formation through mTORC1
      inactivation. Rapamycin treatment did not promote autophagy or degradation of
      OFD1, a negative regulator of ciliogenesis. In contrast, rapamycin treatment
      increased the level of the p27KIP1 (also known as CDKN1B) cyclin-dependent kinase
      inhibitor, and rapamycin-induced ciliogenesis was abrogated in p27KIP1-depleted
      cells. These results indicate that mTORC1 inactivation induces ciliogenesis
      through p27KIP1 upregulation, but not through autophagy. By contrast, glucose
      deprivation or rapamycin treatment shortened the cilium length. Thus, glucose
      deprivation and subsequent inactivation of mTORC1 play dual roles in
      ciliogenesis: triggering primary cilium formation and shortening cilium
      length.This article has an associated First Person interview with the first
      author of the paper.

PMID- 29180514
TI  - Protein localization screening in vivo reveals novel regulators of multiciliated
      cell development and function.
AB  - Multiciliated cells (MCCs) drive fluid flow in diverse tubular organs and are
      essential for the development and homeostasis of the vertebrate central nervous
      system, airway and reproductive tracts. These cells are characterized by dozens
      or hundreds of motile cilia that beat in a coordinated and polarized manner. In
      recent years, genomic studies have not only elucidated the transcriptional
      hierarchy for MCC specification but also identified myriad new proteins that
      govern MCC ciliogenesis, cilia beating and cilia polarization. Interestingly,
      this burst of genomic data has also highlighted that proteins with no obvious
      role in cilia do, in fact, have important ciliary functions. Understanding the
      function of proteins with little prior history of study presents a special
      challenge, especially when faced with large numbers of such proteins. Here, we
      define the subcellular localization in MCCs of ~200 proteins not previously
      implicated in cilia biology. Functional analyses arising from the screen provide
      novel links between actin cytoskeleton and MCC ciliogenesis.

PMID- 29180516
TI  - The EGFR odyssey - from activation to destruction in space and time.
AB  - When cell surface receptors engage their cognate ligands in the extracellular
      space, they become competent to transmit potent signals to the inside of the
      cell, thereby instigating growth, differentiation, motility and many other
      processes. In order to control these signals, activated receptors are endocytosed
      and thoroughly curated by the endosomal network of intracellular vesicles and
      proteolytic organelles. In this Review, we follow the epidermal growth factor
      (EGF) receptor (EGFR) from ligand engagement, through its voyage on endosomes
      and, ultimately, to its destruction in the lysosome. We focus on the spatial and
      temporal considerations underlying the molecular decisions that govern this
      complex journey and discuss how additional cellular organelles - particularly the
      ER - play active roles in the regulation of receptor lifespan. In summarizing the
      functions of relevant molecules on the endosomes and the ER, we cover the order
      of molecular events in receptor activation, trafficking and downregulation, and
      provide an overview of how signaling is controlled at the interface between these
      organelles.

PMID- 29180515
TI  - Migration against the direction of flow is LFA-1-dependent in human hematopoietic
      stem and progenitor cells.
AB  - The recruitment of immune cells during inflammation is regulated by a multi-step
      cascade of cell rolling, activation, adhesion and transmigration through the
      endothelial barrier. Similarly, hematopoietic stem and progenitor cells (HSPCs)
      use this pathway to migrate and home to the bone marrow. After selectin-mediated
      braking, HSPCs migrate on adhesion ligands presented by the vascular endothelium
      including ICAM-1, VCAM-1 or MAdCAM-1. Here, we report that both the KG1a stem
      cell line and primary bone marrow CD34+ HSPCs can migrate against the direction
      of fluid flow on surfaces coated with cell adhesion molecules (CAMs), a behavior
      thus far only reported in T lymphocytes. We demonstrate that KG1a cells and
      primary HSPCs migrate upstream on surfaces presenting ICAM-1, downstream on
      surfaces presenting VCAM-1, and both upstream and downstream on surfaces
      presenting MAdCAM-1. In addition, we demonstrate that KG1a cells and HSPCs
      display upstream migration both on surfaces with multiple CAMs, as well as on
      human umbilical vein endothelial cell (HUVEC) monolayers. By blocking with
      monoclonal antibodies, we show that lymphocyte function-associated antigen-1 (LFA
      1) is the key receptor responsible for upstream migration on the endothelium
      during the trafficking of HSPCs to the bone marrow.This article has an associated
      First Person interview with the first author of the paper.

PMID- 29180518
TI  - Unintentional injury mortality among indigenous communities of Taiwan: trends
      from 2002 to 2013 and evaluation of a community-based intervention.
AB  - INTRODUCTION: Indigenous communities in Taiwan shoulder a disproportionate burden
      of unintentional injury fatalities. We compare unintentional injury mortality
      rate trends among Taiwan's indigenous communities and the general population from
      2002 to 2013, and evaluate potential impact of a community-based injury
      prevention programme on indigenous unintentional injury death rates. METHODS:
      Standardised and crude unintentional injury mortality rates were obtained from
      Taiwan government reports. Segmented linear regression was used to estimate and
      compare unintentional injury mortality rate trends before and after the
      intervention. RESULTS: Between 2002 and 2013, unintentional injury mortality
      rates among Taiwan's indigenous population significantly declined by about 4.5
      deaths per 100 000 each year (p<0.0001). During that time, the unintentional
      injury mortality rate ratio between indigenous Taiwanese and the general
      population significantly decreased by approximately 1% each successive year
      (p=0.02). However, we were unable to detect evidence that the 'Healthy and Safe
      Tribe' programme was associated with a statistically significant decrease in the
      unintentional injury mortality rate trend among indigenous persons (p=0.81).
      CONCLUSION: Taiwanese indigenous communities remain at significantly higher risk
      of unintentional injury death, though the gap may be slowly narrowing. We found
      no evidence that the 'Healthy and Safe Tribe' indigenous injury-prevention
      programme significantly contributed to the nationwide decline in unintentional
      injury mortality among indigenous Taiwanese communities from 2009 to 2013. Future
      interventions to address the disproportionate burden of unintentional injury
      fatalities among indigenous Taiwanese should consider interventions with wider
      coverage of the indigenous population, and complementing grass roots led
      community-based interventions with structural policy interventions as well.

PMID- 29180517
TI  - RDGBalpha localization and function at membrane contact sites is regulated by
      FFAT-VAP interactions.
AB  - Phosphatidylinositol transfer proteins (PITPs) are essential regulators of PLC
      signalling. The PI transfer domain (PITPd) of multi-domain PITPs is reported to
      be sufficient for in vivo function, questioning the relevance of other domains in
      the protein. In Drosophila photoreceptors, loss of RDGBalpha, a multi-domain PITP
      localized to membrane contact sites (MCSs), results in multiple defects during
      PLC signalling. Here, we report that the PITPd of RDGBalpha does not localize to
      MCSs and fails to support function during strong PLC stimulation. We show that
      the MCS localization of RDGBalpha depends on the interaction of its FFAT motif
      with dVAP-A. Disruption of the FFAT motif (RDGBFF/AA) or downregulation of dVAP
      A, both result in mis-localization of RDGBalpha and are associated with loss of
      function. Importantly, the ability of the PITPd in full-length RDGBFF/AA to
      rescue mutant phenotypes was significantly worse than that of the PITPd alone,
      indicating that an intact FFAT motif is necessary for PITPd activity in vivo
      Thus, the interaction between the FFAT motif and dVAP-A confers not only
      localization but also intramolecular regulation on lipid transfer by the PITPd of
      RDGBalpha. This article has an associated First Person interview with the first
      author of the paper.

PMID- 29180519
TI  - Understanding the resistance to creating safer ice hockey: essential points for
      injury prevention.
AB  - INTRODUCTION: Despite the known negative health outcomes of concussions in minor
      level boys' hockey, there has been significant resistance to creating a safer
      game with less body checking. METHODS: To better understand cultural barriers
      that prevent making the sport safer for youth and adolescents, semistructured
      interviews, with 20 ice hockey stakeholders, were conducted and analysed using
      thematic analysis. RESULTS: Through this analysis, two primary concepts arose
      from respondents. The first concept is that body checking, despite the harm it
      can cause, should be done in a respectful sportsmanlike fashion. The second
      concept is the contradiction that the game of ice hockey is both dynamic and
      unchangeable. DISCUSSION: Using structural functionalist theory, we propose an
      argument that the unfortunate perpetuation of violence and body checking in youth
      ice hockey serves to maintain the social order of the game and its culture. Any
      strategies aimed at modifying and promoting healthy behaviour in the game should
      take these concepts into account.

PMID- 29180520
TI  - Heartbeat: Healthcare approaches to reducing adverse outcomes in patients with
      atrial fibrillation.

PMID- 29180521
TI  - Liver injury with direct-acting anticoagulants: has the fog cleared?

PMID- 29180522
TI  - Integrated Resistance Analysis of CERTAIN-1 and CERTAIN-2 Studies in Hepatitis C
      Virus-Infected Patients Receiving Glecaprevir and Pibrentasvir in Japan.
AB  - Glecaprevir and pibrentasvir are hepatitis C virus (HCV) pangenotypic inhibitors
      targeting NS3/4A protease and NS5A, respectively. This once-daily, fixed-dose
      combination regimen demonstrated high sustained virologic response 12 weeks
      postdosing (SVR12) rates in CERTAIN-1 and CERTAIN-2 studies in Japanese HCV
      infected patients, with a low virologic failure rate (1.2%). There were no
      virologic failures among direct-acting antiviral (DAA)-treatment-naive genotype
      1a (GT1a) (n = 4)-, GT1b (n = 128)-, and GT2 (n = 97)-infected noncirrhotic
      patients treated for 8 weeks or among GT1b (n = 38)- or GT2 (n = 20)-infected
      patients with compensated cirrhosis treated for 12 weeks. Two of 33 DAA
      experienced and 2 of 12 GT3-infected patients treated for 12 weeks experienced
      virologic failure. Pooled resistance analysis, grouped by HCV subtype, treatment
      duration, prior treatment experience, and cirrhosis status, was conducted. Among
      DAA-naive GT1b-infected patients, the baseline prevalence of NS3-D168E was 1.2%,
      that of NS5A-L31M was 3.6%, and that of NS5A-Y93H was 17.6%. Baseline
      polymorphisms in NS3 or NS5A were less prevalent in GT2, with the exception of
      the common L/M31 polymorphism in NS5A. Among DAA-experienced GT1b-infected
      patients (30/32 daclatasvir plus asunaprevir-experienced patients), the baseline
      prevalence of NS3-D168E/T/V was 48.4%, that of NS5A-L31F/I/M/V was 81.3%, that of
      the NS5A P32deletion was 6.3%, and that of NS5A-Y93H was 59.4%. Common baseline
      polymorphisms in NS3 and/or NS5A had no impact on treatment outcomes in GT1- and
      GT2-infected patients; the impact on GT3-infected patients could not be assessed
      due to the enrollment of patients infected with diverse subtypes and the limited
      number of patients. The glecaprevir-pibrentasvir combination regimen allows a
      simplified treatment option without the need for HCV subtyping or baseline
      resistance testing for DAA-naive GT1- or GT2-infected patients. (The CERTAIN-1
      and CERTAIN-2 studies have been registered at ClinicalTrials.gov under
      identifiers NCT02707952 and NCT02723084, respectively.).

PMID- 29180523
TI  - Efficacy of Novel Antistaphylococcal Ectolysin P128 in a Rat Model of Methicillin
      Resistant Staphylococcus aureus Bacteremia.
AB  - Staphylococcus aureus causes systemic infections with high morbidity and
      mortality, and the emergence of drug-resistant strains is a rapidly growing
      clinical concern. Novel therapeutic agents are required to tackle S. aureus
      infections. P128 is a bacteriophage-derived chimeric ectolysin with potent and
      rapid bactericidal activity against S. aureus In the present study, the efficacy
      of P128 was evaluated in a newly developed rat model of S. aureus bacteremia.
      Prior to in vivo testing, P128 was shown to be stable in whole blood by
      incubation in rat blood for up to 6 h and testing its bactericidal activity
      against the methicillin-resistant S. aureus isolate USA300. Rats succumbed to
      intravenous challenge with 109 CFU of S. aureus USA300, resulting in 80 to 100%
      mortality by day 14. Evaluation of the bacterial load in various organs at 96 h
      postinfection revealed high bacterial counts in the kidney, and this correlated
      with the presence of renal abscesses. Treatment of infected animals with P128
      either by intravenous bolus administration via tail vein or by 1-h infusion via
      the jugular vein at 2 h postinfection resulted in the dose-dependent survival of
      rats. P128 treatment also resulted in very few or no abscesses in the kidneys.
      These data show that P128 is stable in the physiological milieu and that
      intravenous treatment with P128 is highly effective in rescuing rats from S.
      aureus bacteremia. P128 can be a novel therapeutic option for treatment of S.
      aureus systemic infections.

PMID- 29180524
TI  - Safety and Pharmacokinetics of the Aminomethylcycline Antibiotic Omadacycline
      Administered to Healthy Subjects in Oral Multiple-Dose Regimens.
AB  - Omadacycline, a first-in-class aminomethylcycline antibiotic, is related to
      tetracyclines but is structurally modified to circumvent mechanisms of resistance
      to tetracyclines. Omadacycline demonstrates potent activity against a broad range
      of pathogens, including drug-resistant strains, and is in late-stage development
      for treatment of acute bacterial skin and skin structure infections and community
      acquired bacterial pneumonia. Previous studies support an intravenous-to-oral
      transition regimen with 300-mg once-daily oral dosing. This phase 1 study
      investigated the pharmacokinetics and safety/tolerability of multiple oral
      omadacycline doses higher than 300 mg. Using a 3-period crossover design, healthy
      adults were randomized to receive oral omadacycline at 300, 450, and 600 mg in
      variable sequence (n = 26) or placebo (n = 7) once daily for 5 consecutive days
      per period. In plasma, omadacycline maximum concentration and total exposure
      increased with increasing dose but were less than dose proportional. The kinetics
      of omadacycline plasma accumulation were similar between dose levels; exposure on
      day 5 was ~50% higher than that on day 1. Omadacycline plasma concentrations on
      day 1 of 450-mg dosing were similar to those on day 5 of 300-mg dosing. All doses
      were generally well tolerated, but the 600-mg dose was associated with more
      gastrointestinal adverse events.

PMID- 29180525
TI  - Increasing Antimicrobial Resistance in Nontyphoidal Salmonella Isolates in
      Australia from 1979 to 2015.
AB  - Australia has high and increasing rates of salmonellosis. To date, the serovar
      distribution and associated antimicrobial resistance (AMR) patterns of
      nontyphoidal Salmonella enterica (NTS) in Australia have not been assessed. Such
      information provides critical knowledge about AMR in the food chain and informs
      decisions about public health. We reviewed longitudinal data on NTS in two
      Australian states over a 37-year period, between 1979 and 2015, and antimicrobial
      resistance since 1984. Overall, 17% of isolates were nonsusceptible to at least
      one antimicrobial, 4.9% were nonsusceptible to ciprofloxacin, and 0.6% were
      nonsusceptible to cefotaxime. In total, 2.5% of isolates were from invasive
      infections, with no significant difference in AMR profiles between invasive and
      noninvasive isolates. Most isolates with clinically relevant AMR profiles were
      associated with travel, particularly to Southeast Asia, with multiple
      "incursions" of virulent and resistant clones into Australia. Our findings
      represent the largest longitudinal surveillance system for NTS in Australia and
      provide valuable public health knowledge on the trends and distribution of AMR in
      NTS. Ongoing surveillance is critical to identify local emergence of resistant
      isolates.

PMID- 29180526
TI  - Antibacterial and Sterilizing Effect of Benzylpenicillin in Tuberculosis.
AB  - The modern chemotherapy era started with Fleming's discovery of benzylpenicillin.
      He demonstrated that benzylpenicillin did not kill Mycobacterium tuberculosis In
      this study, we found that >64 mg/liter of static benzylpenicillin concentrations
      killed 1.16 to 1.43 log10 CFU/ml below starting inoculum of extracellular and
      intracellular M. tuberculosis over 7 days. When we added the beta-lactamase
      inhibitor avibactam, benzylpenicillin maximal kill (Emax) of extracellular log
      phase-growth M. tuberculosis was 6.80 +/- 0.45 log10 CFU/ml at a 50% effective
      concentration (EC50) of 15.11 +/- 2.31 mg/liter, while for intracellular M.
      tuberculosis it was 2.42 +/- 0.14 log10 CFU/ml at an EC50 of 6.70 +/- 0.56
      mg/liter. The median penicillin (plus avibactam) MIC against South African
      clinical M. tuberculosis strains (80% either multidrug or extensively drug
      resistant) was 2 mg/liter. We mimicked human-like benzylpenicillin and avibactam
      concentration-time profiles in the hollow-fiber model of tuberculosis (HFS-TB).
      The percent time above the MIC was linked to effect, with an optimal exposure of
      >=65%. At optimal exposure in the HFS-TB, the bactericidal activity in log-phase
      growth M. tuberculosis was 1.44 log10 CFU/ml/day, while 3.28 log10 CFU/ml of
      intracellular M. tuberculosis was killed over 3 weeks. In an 8-week HFS-TB study
      of nonreplicating persistent M. tuberculosis, penicillin-avibactam alone and the
      drug combination of isoniazid, rifampin, and pyrazinamide both killed >7.0 log10
      CFU/ml. Monte Carlo simulations of 10,000 preterm infants with disseminated
      disease identified an optimal dose of 10,000 U/kg (of body weight)/h, while for
      pregnant women or nonpregnant adults with pulmonary tuberculosis the optimal dose
      was 25,000 U/kg/h, by continuous intravenous infusion. Penicillin-avibactam
      should be examined for effect in pregnant women and infants with drug-resistant
      tuberculosis, to replace injectable ototoxic and teratogenic second-line drugs.

PMID- 29180527
TI  - Azithromycin Pharmacodynamics against Persistent Haemophilus influenzae in
      Chronic Obstructive Pulmonary Disease.
AB  - The pharmacodynamic profile of azithromycin against persistent strains of
      nontypeable Haemophilus influenzae (NTHi) from chronic obstructive pulmonary
      disease (COPD) patients was characterized. Azithromycin displayed differential
      concentration-dependent activities (R2 >= 0.988); the pharmacodynamic response
      was attenuated when we compared the "first" and "last" strains of NTHi that
      persisted in the airways of the same patient for 819 days (the 50% effective
      concentration [EC50] increased more than 50 times [0.0821 mg/liter versus 4.23
      mg/liter]). In the hollow-fiber infection model, NTHi viability was maintained
      throughout simulated azithromycin (Zithromax) Z-Pak regimens over 10 days.

PMID- 29180528
TI  - Simple In Vitro Assay To Evaluate the Incorporation Efficiency of Ribonucleotide
      Analog 5'-Triphosphates into RNA by Human Mitochondrial DNA-Dependent RNA
      Polymerase.
AB  - There is a growing body of evidence suggesting that some
      ribonucleoside/ribonucleotide analogs may be incorporated into mitochondrial RNA
      by human mitochondrial DNA-dependent RNA polymerase (POLRMT) and disrupt
      mitochondrial RNA synthesis. An assessment of the incorporation efficiency of a
      ribonucleotide analog 5'-triphosphate by POLRMT may be used to evaluate the
      potential mitochondrial toxicity of the analog early in the development process.
      In this report, we provide a simple method to prepare active recombinant POLRMT.
      A robust in vitro nonradioactive primer extension assay was developed to assay
      the incorporation efficiency of ribonucleotide analog 5'-triphosphates. Our
      results show that many ribonucleotide analogs, including some antiviral compounds
      currently in various preclinical or clinical development stages, can be
      incorporated into newly synthesized RNA by POLRMT and that the incorporation of
      some of them can lead to chain termination. The discrimination (D) values of
      ribonucleotide analog 5'-triphosphates over those of natural ribonucleotide
      triphosphates (rNTPs) were measured to evaluate the incorporation efficiency of
      the ribonucleotide analog 5'-triphosphates by POLRMT. The discrimination values
      of natural rNTPs under the condition of misincorporation by POLRMT were used as a
      reference to evaluate the potential mitochondrial toxicity of ribonucleotide
      analogs. We propose the following criteria for the potential mitochondrial
      toxicity of ribonucleotide analogs based on D values: a safe compound has a D
      value of >105; a potentially toxic compound has a D value of >104 but <105; and a
      toxic compound has a D value of <104 This report provides a simple screening
      method that should assist investigators in designing ribonucleoside-based drugs
      having lower mitochondrial toxicity.

PMID- 29180530
TI  - Nursing issues.

PMID- 29180529
TI  - The ABC of Biofilm Drug Tolerance: the MerR-Like Regulator BrlR Is an Activator
      of ABC Transport Systems, with PA1874-77 Contributing to the Tolerance of
      Pseudomonas aeruginosa Biofilms to Tobramycin.
AB  - A hallmark of biofilms is their tolerance to killing by antimicrobial agents. In
      Pseudomonas aeruginosa, biofilm drug tolerance requires the c-di-GMP-responsive
      MerR transcriptional regulator BrlR. However, the mechanism by which BrlR
      mediates biofilm drug tolerance has not been elucidated. Here, we demonstrate
      that BrlR activates the expression of at least 7 ABC transport systems, including
      the PA1874-PA1875-PA1876-PA1877 (PA1874-77) operon, with chromatin
      immunoprecipitation and DNA binding assays confirming BrlR binding to the
      promoter region of PA1874-77. Insertional inactivation of the 7 ABC transport
      systems rendered P. aeruginosa PAO1 biofilms susceptible to tobramycin or
      norfloxacin. Susceptibility was linked to drug accumulation, with BrlR
      contributing to norfloxacin accumulation in a manner dependent on multidrug
      efflux pumps and the PA1874-77 ABC transport system. Inactivation of the
      respective ABC transport system, furthermore, eliminated the recalcitrance of
      biofilms to killing by tobramycin but not norfloxacin, indicating that drug
      accumulation is not linked to biofilm drug tolerance. Our findings indicate for
      the first time that BrlR, a MerR-type transcriptional activator, activates genes
      encoding several ABC transport systems, in addition to multiple multidrug efflux
      pump genes. Moreover, our data confirm a BrlR target contributing to drug
      tolerance, likely countering the prevailing dogma that biofilm tolerance arises
      from a multiplicity of factors.

PMID- 29180531
TI  - Anion Gap as a Determinant of Ionized Fraction of Divalent Cations in
      Hemodialysis Patients.
AB  - BACKGROUND AND OBJECTIVES: Circulating levels of anions that bind to magnesium
      and calcium are often altered in patients with CKD. However, it is unknown how
      these alterations affect the ionized fraction of magnesium and calcium. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This cross-sectional study involved
      patients on maintenance hemodialysis and patients not on dialysis who visited the
      outpatient department of nephrology. We collected whole-blood samples to measure
      ionized magnesium and calcium concentrations. Adjusted anion gap was calculated
      as an integrative index of unmeasured anions. RESULTS: A total of 118 patients on
      hemodialysis and 112 patients not on dialysis were included. Although the
      prevalence of hypermagnesemia defined by total magnesium was much higher in
      patients on hemodialysis than in patients not on dialysis (69% versus 12%;
      P<0.001), the prevalence of hypermagnesemia defined by ionized magnesium did not
      differ significantly (13% versus 18%; P=0.28). Among patients on hemodialysis
      with high total magnesium, 83% had normal or low ionized magnesium. Consequently,
      the mean ionized fraction of magnesium in patients on hemodialysis was
      significantly lower than that in patients not on dialysis (51% versus 63%;
      P<0.001). Similarly, the mean ionized fraction of calcium in patients on
      hemodialysis was lower than that in patients not on dialysis (55% versus 56%;
      P<0.001). In patients on hemodialysis who had a higher adjusted anion gap than
      patients not on dialysis (mean [SD]: 14.1 [2.2] versus 5.1 [3.1]), the ionized
      fractions of magnesium and calcium were inversely associated with the adjusted
      anion gap. Furthermore, the anion gap significantly improved predictions of
      ionized magnesium and calcium in patients on hemodialysis. CONCLUSIONS: Anions
      that accumulate in patients on hemodialysis contribute to the lower ionized
      fraction of magnesium and calcium. Equations that incorporate the anion gap
      provide better predictions of ionized magnesium and calcium in patients on
      hemodialysis.

PMID- 29180532
TI  - To sell or not to sell: cigarette sales in alcohol-licenced premises.
AB  - OBJECTIVE: To obtain insight into tobacco retailing by alcohol-licenced premises,
      in order to understand the financial importance of tobacco sales for such
      retailers. METHOD: Data were collected by a telephone survey of 1042 clubs,
      hotels and packaged liquor outlets in New South Wales, Australia. The response
      rate was 86.1%. Qualitative and quantitative data were obtained. Logistic and
      linear regression were used to determine factors associated with the probability
      of selling and stopping selling and the importance of cigarette sales. RESULTS:
      More than a third (36.4%) of premises contacted did not sell cigarettes. 147 (an
      estimated 18.1% of those who had ever sold) had stopped selling. There were
      significant differences in the probability of selling, in the reported importance
      of cigarette sales and in the probability of stopping selling, between different
      outlet types and other outlet characteristics (number of gaming machines,
      proximity of nearest alternative tobacco retailer and remoteness). Outlets where
      alcohol can be consumed were more likely to rate cigarette sales as 'not
      important' than 'important'. CONCLUSIONS: Despite claims by tobacco companies
      that tobacco sales are important for many Australian retailers, tobacco sales
      appear to be of limited importance for alcohol-licenced premises. This means that
      opposition to stopping tobacco sales where alcohol is consumed and/or sold may be
      less than expected.

PMID- 29180533
TI  - Did independent and convenience (small) retailers comply with standardised
      tobacco packaging in the UK?

PMID- 29180534
TI  - Tobacco control in California compared with the rest of the USA: trends in adult
      per capita cigarette consumption.
AB  - BACKGROUND: In the 1990s, California led the USA in state-level tobacco control
      strategies. However, after 2000, California lost ground on cigarette taxes,
      although it maintained higher levels of smoke-free homes among smokers. METHODS:
      Trends in per capita cigarette consumption were assessed through taxed sales data
      and from self-report in repeated national cross-sectional surveys. Linear
      regressions identified changes in trends after year 2000 separately for
      California and the rest of the USA. Using data from each state, a linear
      regression tested the association between different tobacco control strategies
      and per capita consumption. Change in self-reported per capita consumption was
      partitioned into contributions associated with initiation, quitting and reduction
      in cigarette consumption level. RESULTS: Both taxed cigarette sales and per
      capita consumption declined rapidly in the USA from 1985 to 2015. Declines were
      particularly fast in California before 2000 but slowed thereafter. In 2014, per
      capita consumption in California was 29.4 packs/adult/year, but 90% higher in the
      rest of the USA. Modelling state-level data, every $1 increase in cigarette taxes
      reduced consumption by 4.8 (95% CI 2.9 to 6.8) packs/adult/year. Every 5%
      increase in the proportion of smokers with smoke-free homes reduced consumption
      by 8.0 (95% CI 7.0 to 8.9) packs/adult/year. The different patterns in California
      and the rest of the USA are at least partially explained by these two variables.
      The slow down in per capita consumption in California can be attributed to
      changes in initiation, quitting and especially smokers reducing their consumption
      level. CONCLUSIONS: Tobacco control strategies need to be continually updated to
      maintain momentum towards a smoke-free society.

PMID- 29180535
TI  - Radiotherapy and CTLA-4 Blockade Shape the TCR Repertoire of Tumor-Infiltrating T
      Cells.
AB  - Immune checkpoint inhibitors activate T cells to reject tumors. Unique tumor
      mutations are key T-cell targets, but a comprehensive understanding of the nature
      of a successful antitumor T-cell response is lacking. To investigate the T-cell
      receptor (TCR) repertoire associated with treatment success versus failure, we
      used a well-characterized mouse carcinoma that is rejected by CD8 T cells in mice
      treated with radiotherapy (RT) and anti-CTLA-4 in combination, but not as
      monotherapy, and comprehensively analyzed tumor-infiltrating lymphocytes (TILs)
      by high-throughput sequencing of the TCRBeta CDR3 region. The combined treatment
      increased TIL density and CD8/CD4 ratio. Assessment of the frequency of T-cell
      clones indicated that anti-CTLA-4 resulted in fewer clones and a more oligoclonal
      repertoire compared with untreated tumors. In contrast, RT increased the CD8/CD4
      ratio and broadened the TCR repertoire, and when used in combination with anti
      CTLA-4, these selected T-cell clones proliferated. Hierarchical clustering of
      CDR3 sequences showed a treatment-specific clustering of TCRs that were shared by
      different mice. Abundant clonotypes were commonly shared between animals and yet
      treatment-specific. Analysis of amino-acid sequence similarities revealed a
      significant increase in the number and richness of dominant CDR3 motifs in tumors
      treated with RT + anti-CTLA-4 compared with control. The repertoire of TCRs
      reactive with a single tumor antigen recognized by CD8+ T cells was heterogeneous
      but highly clonal, irrespective of treatment. Overall, data support a model
      whereby a diverse TCR repertoire is required to achieve tumor rejection and may
      underlie the synergy between RT and CTLA-4 blockade. Cancer Immunol Res; 6(2);
      139-50. (c)2017 AACR.

PMID- 29180536
TI  - High-Affinity GD2-Specific CAR T Cells Induce Fatal Encephalitis in a Preclinical
      Neuroblastoma Model.
AB  - The GD2 ganglioside, which is abundant on the surface of neuroblastoma cells, is
      targeted by an FDA-approved therapeutic monoclonal antibody and is an attractive
      tumor-associated antigen for cellular immunotherapy. Chimeric antigen receptor
      (CAR)-modified T cells can have potent antitumor activity in B-cell malignancies,
      and trials to harness this cytolytic activity toward GD2 in neuroblastoma are
      under way. In an effort to enhance the antitumor activity of CAR T cells that
      target GD2, we generated variant CAR constructs predicted to improve the
      stability and the affinity of the GD2-binding, 14G2a-based, single-chain variable
      fragment (scFv) of the CAR and compared their properties in vivo We included the
      E101K mutation of GD2 scFv (GD2-E101K) that has enhanced antitumor activity
      against a GD2+ human neuroblastoma xenograft in vivo However, this enhanced
      antitumor efficacy in vivo was concomitantly associated with lethal central
      nervous system (CNS) toxicity comprised of extensive CAR T-cell infiltration and
      proliferation within the brain and neuronal destruction. The encephalitis was
      localized to the cerebellum and basal regions of the brain that display low
      amounts of GD2. Our results highlight the challenges associated with target
      antigens that exhibit shared expression on critical normal tissues. Despite the
      success of GD2-specific antibody therapies in the treatment of neuroblastoma, the
      fatal neurotoxicity of GD2-specific CAR T-cell therapy observed in our studies
      suggests that GD2 may be a difficult target antigen for CAR T-cell therapy
      without additional strategies that can control CAR T-cell function within the
      CNS. Cancer Immunol Res; 6(1); 36-46. (c)2017 AACR.

PMID- 29180537
TI  - A cross-sectional study examining associations between substance use frequency,
      problematic use and STIs among youth living with HIV.
AB  - OBJECTIVES: This study sought to examine the prevalence of STIs and whether
      substance use frequency and/or problematic use-specifically alcohol, marijuana
      and other drugs-was associated with having an STI diagnosis among youth living
      with HIV (YLWH) METHODS: A sample of 823 YLWH were recruited at 14 adolescent HIV
      clinics through the Adolescent Medicine Trials Network for HIV Interventions.
      Study staff abstracted STI data from medical records for up to 26 weeks prior to
      participants' completing a cross-sectional survey including the ASSIST (Alcohol,
      Smoking and Substance Involvement Screening Test), which measures substance use
      frequency and consequences. RESULTS: Almost one-third of youth had been diagnosed
      with an STI (30.5%) at the time of their baseline assessment. In multivariable
      analyses, those who engaged in weekly or greater marijuana use (adjusted OR
      (AOR)=10.66, 95% CI: 4.39 to 25.87, P<0.001) had an increased odds of being
      diagnosed with an STI. Additionally, youth who met alcohol use criteria for
      moderate (AOR=5.23, 95% CI: 2.50 to 10.93, P<0.001) and high risk (AOR=6.53, 95%
      CI: 1.20 to 35.68, P<0.05) alcohol use had an increased odds of being diagnosed
      with an STI compared with low-risk alcohol users. CONCLUSIONS: Study findings
      underscore the need to investigate the role of greater frequency of marijuana use
      and problematic alcohol use in STI incidence among YLWH. Given the associations
      between both substance use frequency and problematic use in STI diagnoses among
      YLWH seen in HIV care settings, clinicians should use validated substance use
      screening tools which capture both frequencies and consequences in order to
      identify YLWH who may need further evaluation and treatment.

PMID- 29180539
TI  - Chitotriosidase: shucking the role of microglia in amyotrophic lateral sclerosis.

PMID- 29180538
TI  - Prevalence and sociodemographic correlates of cervicovaginal human papillomavirus
      (HPV) carriage in a cross-sectional, multiethnic, community-based female Asian
      population.
AB  - OBJECTIVES: Cervical cancer is a largely preventable disease, and the strategic
      implementation of a cervical cancer prevention programme is partly dependent on
      the impact of human papillomavirus (HPV) infection interpreted within the context
      of the country's sociodemographic attributes. The objective of this study is to
      determine the prevalence of cervicovaginal HPV infection among a healthy,
      community-based, multiethnic Malaysian population. The HPV prevalence was
      subsequently correlated to the individual's sociodemographics and
      sexual/reproductive history. Of significance, the observed prevalence captured
      was in a birth cohort not included in the national school-based HPV vaccination
      programme. METHODS: This was a cross-sectional study where 1293 healthy women
      aged between 18 and 60 years were recruited via convenience sampling from five
      community-based clinics in Selangor, Malaysia. Cervicovaginal self-samples were
      obtained and DNA was extracted for HPV detection and genotyping. A comprehensive
      questionnaire was administered to determine the sociodemographics and behavioural
      patterns of participants. RESULTS: The median age at enrolment was 37 years old
      (IQR: 30-47). In total, 86/1190 (7.2%) of the samples collected were positive for
      HPV infection, with the highest HPV prevalence (11.9%) detected in the subgroup
      of 18-24 years old. The top three most prevalent HPV genotypes were HPV 16, 52
      and 58. The independent risk factors associated with higher rates of HPV
      infection included Indian ethnicity, widowed status and women with partners who
      are away from home for long periods and/or has another sexual partner.
      CONCLUSIONS: The overall prevalence of HPV infection in this Malaysian
      multiethnic population was 7.2%, with 6.5% being high-risk genotypes. The top
      three most common high-risk HPV types were HPV 16, 52 and 58. This information is
      important for the planning of primary (HPV vaccination) and secondary (screening)
      cervical cancer prevention programmes in Malaysia.

PMID- 29180540
TI  - Reducing alarms in the NICU.

PMID- 29180541
TI  - Neonatal brain injuries in England: population-based incidence derived from
      routinely recorded clinical data held in the National Neonatal Research Database.
AB  - OBJECTIVE: In 2015, the Department of Health in England announced an ambition to
      reduce 'brain injuries occurring during or soon after birth'. We describe the
      development of a pragmatic case definition and present annual incidence rates.
      DESIGN: Retrospective cohort study using data held in the National Neonatal
      Research Database (NNRD) extracted from neonatal electronic patient records from
      all National Health Service (NHS) neonatal units in England, Wales and Scotland.
      In 2010-2011, population coverage in the NNRD was incomplete, hence rate
      estimates are presented as a range; from 2012, population coverage is complete,
      and rates (95% CIs) are presented. Rates are per 1000 live births. SETTING: NHS
      neonatal units in England. PATIENTS: Infants admitted for neonatal care;
      denominator: live births in England. MAIN OUTCOME MEASURE: 'Brain injuries
      occurring at or soon after birth' defined as infants with seizures, hypoxic
      ischaemic encephalopathy, stroke, intracranial haemorrhage, central nervous
      system infection and kernicterus and preterm infants with cystic periventricular
      leucomalacia. RESULTS: In 2010, the lower estimate of the rate of 'Brain injuries
      occurring at or soon after birth' in England was 4.53 and the upper estimate was
      5.19; in 2015, the rate was 5.14 (4.97, 5.32). For preterm infants, the
      population incidence in 2015 was 25.88 (24.51, 27.33) and 3.47 (3.33, 3.62) for
      term infants. Hypoxic-ischaemic encephalopathy was the largest contributor to
      term brain injury, and intraventricular/periventricular haemorrhage was the
      largest contributor to preterm brain injury. CONCLUSIONS: Annual incidence rates
      for brain injuries can be estimated from data held in the NNRD; rates for
      individual conditions are consistent with published rates. Routinely recorded
      clinical data can be used for national surveillance, offering efficiencies over
      traditional approaches.

PMID- 29180542
TI  - Myocardial revascularisation in high-risk subjects.

PMID- 29180543
TI  - Multiple Practical Facts and Ideas to Improve Family Medicine Care.
AB  - Seconds count in a study on the best electronic health note format to reduce
      medical record charting time and increase accuracy. Directly observed family
      physician work is compared with Current Procedural Terminology (CPT) coding
      examples and notably under-recognized. This issue contains articles from single
      practices that that implemented new methods of care and other reports on practice
      innovations that can be more broadly implemented. We have articles on opioid
      medication use for acute low back pain in primary care, an electronic chronic
      pain consult service, a key question to identify potential opioid misuse risk,
      and newly implemented screening for other substances of abuse. Omissions (or
      gaps) in care are also highlighted: from the common types of omissions identified
      by primary care clinicians, self-reported low levels of substance use screening
      by family medicine prenatal care providers, and inadequate and inadequately
      available hospital discharge summaries. In addition, the most important alarm
      symptoms for a cancer diagnosis are reported.

PMID- 29180544
TI  - Dynamic Electronic Health Record Note Prototype: Seeing More by Showing Less.
AB  - INTRODUCTION: Cluttered documentation may contribute adversely to physician
      readers' cognitive load, inadvertently obscuring high-value information with less
      valuable information. We test the hypothesis that a novel, collapsible
      assessment, plan, subjective, objective (APSO) note design would be faster, more
      accurate, and more satisfying to use than a conventional electronic health record
      (EHR) subjective, objective, assessment, plan (SOAP) note for finding information
      needed for ambulatory chronic disease care. METHODS: We iteratively developed
      physician clinic note prototypes with features designed to emphasize more
      important information and de-emphasize less clinically relevant information.
      Sixteen primary care physicians reviewed comparable clinic notes with the 4 note
      styles presented in random order to find key information in the notes during
      timed tasks. The 4 note styles were denoted A (traditional SOAP note), B (2
      column APSO note), C (collapsible APSO note), and D (2-column collapsible APSO
      note). The 4 unique note styles were designed to have equal amounts of
      information in each section. We simulated their utility for clinical practice by
      imposing time limits and by interrupting 1 of the tasks with a typical clinical
      interruption. For each session, we recorded audio, computer-screen activity, eye
      tracking, and made field notes. We obtained usability ratings (System Usability
      Scale), new feature preference ratings, and performed semistructured post-task
      interviews with subsequent content analysis. We compared the effectiveness of the
      4 note styles by measuring time on task, task success (accuracy), and effort as
      measured by NASA Task Load Index. RESULTS: Note styles C and D were significantly
      faster than A and B for the Review of Systems and Physical Examination tasks, as
      we expected. Notes B and C had the best success (finding requested data) scores.
      Users strongly endorsed all the new note features incorporated into the new note
      prototypes. Previously expressed concerns about temporarily hiding parts of the
      note (using the accordion display design pattern) were allayed. Usability ratings
      for note A were worst but comparably better for note styles B, C, and D.
      DISCUSSION: The new APSO note prototypes performed better than the traditional
      SOAP note format for speed, task success (accuracy), and usability for physician
      users acquiring information needed for a typical chronic disease visit in primary
      care. Moving Assessment and Plan to the top is 1 easily accomplished feature
      change. Innovative documentation displays of EHR data can safely improve
      information display without eliminating data from the record of the visit.

PMID- 29180545
TI  - Implementation of a Standardized Medication Therapy Management Plus Approach
      within Primary Care.
AB  - PURPOSE: The purpose of this study was to implement a clinical pharmacist-led
      medication therapy management (MTM) service within a primary-care setting that is
      enhanced by 1) a clinical decision support system (CDSS) that includes a unique
      combination of medication risk mitigation factors, which aids the pharmacist in
      interpreting the medication profile, and 2) pharmacogenomics (PGx) testing.
      METHODS: This was a service implementation study, whereby Medicare beneficiaries
      were eligible if they were patients of Elmwood Family Physicians, a private
      family, primary care practice with 2 locations in New Jersey, and were on at
      least 7 medications. Patients had a medication reconciliation completed by a
      pharmacist and performed a PGx buccal swab. Patient information was run through a
      CDSS to aid the pharmacist with screening for multidrug interactions and
      assessing patient's medication-related risks. The output of the CDSS was used to
      create recommendations and provide a consult to the physicians. Recommendations
      were followed up by return of the consult. RESULTS: Enrolled patients used a mean
      (+/- standard deviation) of 12.1 (+/- 4.6) medications. The turnaround time for
      the MTM Plus consults was 11.7 (+/- 6.2) days. During the consults, the
      pharmacist identified 138 medication-related problems (MRPs). The most common
      MRPs were drug-drug interactions (29.0%) and drug-gene interactions (DGIs;
      24.6%). CONCLUSION: Implementing a clinical pharmacist-led MTM Plus service in
      the primary care setting is feasible. This study highlights that DGIs are common
      in older adults in family practice and indicates that PGx testing identifies
      additional MRPs that may otherwise go unnoticed in these patients. The
      experiences we shared can aid other clinicians in establishing successful MTM
      Plus services. Future studies should also measure the impact of such personalized
      medicine services on economic, clinical, and humanistic outcomes. This study has
      been registered with ClinicalTrials.gov (study No. NCT02748148).

PMID- 29180546
TI  - Impact of a Novel Wellness Group Visit Model on Obesity and Behavior Change.
AB  - BACKGROUND: Increasing weight-related illness in the United States has led to
      120,000 preventable deaths annually and soaring medical costs. Treating patients
      in a group setting may be more effective than traditional care (TC) in achieving
      behavioral change. We studied a wellness-group (WG) model to determine whether it
      could generate sustained behavioral change and weight loss in a subset of
      patients. METHODS: 99 patients with a body mass index (BMI) >30 kg/m2 from 1
      family practice volunteered to participate in a 15-visit WG co-led by a family
      physician and dietitian. We compared these WG patients with 190 patients who had
      a BMI >30 kg/m2 and who received TC in the form of an annual physical during the
      same time period. The patients were mostly white, highly educated, and of middle
      to-high-income households. All patients were surveyed on their ability to sustain
      12 wellness behaviors 3 months after completing their WG or physical. Patients
      were not paid to complete the survey. We reviewed medical charts for weight, BMI,
      blood pressure, lipids, and glycohemoglobin before and at least 1 year after the
      WG or physical. WG patients' weights were recorded at the beginning and end of
      the WG as was the weight from their most recent office visit. RESULTS: WG
      patients were more likely to report sustaining 12 of 12 wellness behaviors than
      patients who received TC with an annual physical. At 1 year, WG patients also
      lost more weight than TC patients (-13.21 pounds for WG vs +1.94 pounds for TC)
      and achieved greater reduction in their systolic blood pressure (-6.96 mm Hg for
      WG vs -1.13 mm Hg for TC). Average weight gained after the WG was 6.9 pounds.
      Among WG patients, 61% lost a clinically relevant amount of weight (>5%). Of the
      WG patients who lost clinically relevant weight, 71% were able to maintain at
      least half of their weight loss 3 years later. CONCLUSIONS: An observational
      study of a novel WG model showed that WG patients sustained wellness behaviors
      and weight loss over time when compared with patients who received TC.

PMID- 29180547
TI  - The Full Scope of Family Physicians' Work Is Not Reflected by Current Procedural
      Terminology Codes.
AB  - BACKGROUND: The purpose of this study was to characterize the content of family
      physician (FP) clinic encounters, and to count the number of visits in which the
      FPs addressed issues not explicitly reportable by 99211 to 99215 and 99354
      Current Procedural Terminology (CPT) codes with current reimbursement methods and
      based on examples provided in the CPT manual. METHODS: The data collection
      instrument was modeled on the National Ambulatory Medical Care Survey. Trained
      assistants directly observed every other FP-patient encounter and recorded every
      patient concern, issue addressed by the physician (including care barriers
      related to health care systems and social determinants), and treatment ordered in
      clinics affiliated with 10 residencies of the Residency Research Network of
      Texas. A visit was deemed to include physician work that was not explicitly
      reportable if the number or nature of issues addressed exceeded the definitions
      or examples for 99205/99215 or 99214 + 99354 or a preventive service code,
      included the physician addressing health care system or social determinant
      issues, or included the care of a family member. RESULTS: In 982 physician
      patient encounters, patients raised 517 different reasons for visit (total, 5278;
      mean, 5.4 per visit; range, 1 to 16) and the FPs addressed 509 different issues
      (total issues, 3587; mean, 3.7 per visit; range, 1 to 10). FPs managed 425
      different medications, 18 supplements, and 11 devices. A mean of 3.9 chronic
      medications were continued per visit (range, 0 to 21) and 4.6 total medications
      were managed (range, 0 to 22). In 592 (60.3%) of the visits the FPs did work that
      was not explicitly reportable with available CPT codes: 582 (59.3%) addressed
      more numerous issues than explicitly reportable, 64 (6.5%) addressed system
      barriers, and 13 (1.3%) addressed concerns for other family members. CONCLUSIONS
      AND RELEVANCE: FPs perform cognitive work in a majority of their patient
      encounters that are not explicitly reportable, either by being higher than the
      CPT example number of diagnoses per code or the type of problems addressed, which
      has implications for the care of complex multi-morbid patients and the growth of
      the primary care workforce. To address these limitations, either the CPT codes
      and their associated rules should be updated to reflect the realities of family
      physicians' practices or new billing and coding approaches should be developed.

PMID- 29180548
TI  - Primary Care Providers' Perspectives on Errors of Omission.
AB  - BACKGROUND: Despite recent focus on patient safety in primary care, little
      attention has been paid to errors of omission, which represent significant gaps
      in care and threaten patient safety in primary care but are not well studied or
      categorized. The purpose of this study was to develop a typology of errors of
      omission from the perspectives of primary care providers (PCPs) and understand
      what factors within practices lead to or prevent these omissions. METHODS: A
      qualitative descriptive design was used to collect data from 26 PCPs, both
      physicians and nurse practitioners, from the New York State through individual
      interviews. One researcher conducted all interviews, which were audiotaped,
      transcribed verbatim, and analyzed in ATLAS.ti, Berlin by 3 researchers using
      content analysis. They immersed themselves into data, read transcripts
      independently, and conducted inductive coding. The final codes were linked to
      each other to develop the typology of errors of omission and the themes. Data
      saturation was reached at the 26th interview. RESULTS: PCPs reported that
      omitting patient teaching, patient followup, emotional support, and addressing
      mental health needs were the main categories of errors of omission. PCPs
      perceived that time constraints, unplanned patient visits and emergencies, and
      administrative burden led to these gaps in care. They emphasized that
      organizational support and infrastructure, effective teamwork and communication,
      and preparation for the patient encounter were important safeguards to prevent
      errors of omission within their practices. DISCUSSION: Errors of omission are
      common in primary care and could threaten patient safety. Efforts to eliminate
      them should focus on strengthening organizational attributes of practices,
      improving teamwork and communication, and assigning manageable workload to PCPs.
      CONCLUSIONS: Practice and policy change is necessary to address gaps in care and
      prevent them before they result in patient harm.

PMID- 29180549
TI  - Family Physicians' Perceived Prevalence, Safety, and Screening for Cigarettes,
      Marijuana, and Electronic-Nicotine Delivery Systems (ENDS) Use during Pregnancy.
AB  - OBJECTIVE: Assess perceptions of prevalence, safety, and screening practices for
      cigarettes and secondhand smoke exposure (SHSe), marijuana (and synthetic
      marijuana), electronic nicotine delivery systems (ENDS; eg, e-cigarettes),
      nicotine-replacement therapy (NRT), and smoking-cessation medications during
      pregnancy, among primary care physicians (PCPs) providing obstetric care.
      METHODS: A web-based, cross-sectional survey was e-mailed to 3750 US physicians
      (belonging to organizations within the Council of Academic Family Medicine
      Educational Research Alliance). Several research groups' questions were included
      in the survey. Only physicians who reported providing "labor and delivery"
      obstetric care responded to questions related to the study objectives. RESULTS: A
      total of 1248 physicians (of 3750) responded (33.3%) and 417 reported providing
      labor and delivery obstetric care. Obstetric providers (N = 417) reported
      cigarette (54%), marijuana (49%), and ENDS use (24%) by "Some (6% to 25%)"
      pregnant women, with 37% endorsing that "Very Few (1% to 5%)" pregnant women used
      ENDS. Providers most often selected that very few pregnant women used NRT (45%),
      cessation medications (ie, bupropion or varenicline; 37%), and synthetic
      marijuana (23%). Significant proportions chose "Do not Know" for synthetic
      marijuana (58%) and ENDS (27%). Over 90% of the sample perceived that use of or
      exposure to cigarettes (99%), synthetic marijuana (99%), SHS (97%), marijuana
      (92%), or ENDS (91%) were unsafe during pregnancy, with the exception of NRT
      (44%). Providers most consistently screened for cigarette (85%) and marijuana use
      (63%), followed by SHSe in the home (48%), and ENDS (33%) and synthetic marijuana
      use (28%). Fewer than a quarter (18%) screened consistently for all substances
      and SHSe. One third (32%) reported laboratory testing for marijuana and 3%
      reported laboratory testing for smoking status. CONCLUSION: This sample of PCPs
      providing obstetric care within academic settings perceived cigarettes,
      marijuana, and ENDS use to be prevalent and unsafe during pregnancy.
      Opportunities for increased screening during pregnancy across these substances
      were apparent.

PMID- 29180550
TI  - Information Transfer and the Hospital Discharge Summary: National Primary Care
      Provider Perspectives of Challenges and Opportunities.
AB  - PURPOSE: The hospital discharge summary (HDS) serves as a critical method of
      patient information transfer between hospitalist and primary care provider (PCP).
      This study was designed to increase our understanding of PCP preferences for, and
      perceived deficiencies in, the discharge summary. METHODS: We designed a mail
      survey that was sent to a random sample of 800 American Academy of Family
      Physicians members nationally. The survey response rate was 59%. We analyzed the
      availability of summaries at hospital followup, whether all desired information
      was contained in the summary and whether certain specific items were completed.
      Provider subgroup analysis was performed. RESULTS: The strongest predictor of
      discharge summary availability at posthospital followup is direct access to
      inpatient data. Respondents (27.5%) had a summary available 0% to 40% of the
      time, 41.4% noted availability 41% to 80% of the time and 31.1% >80% of the time;
      if a provider had access to inpatient data they tended to have a discharge
      summary available to them (P < .0001). Providers also described significant
      content deficits: 26.5% of providers noted the summary contained all information
      needed 0% to 40% of the time, 48.5% of providers noted this 41% to 80% of the
      time and only 25% >80% of the time. Specific summary items considered "very
      important" by providers included medication list (94% of respondents), diagnosis
      list (89%), and treatment provided (87%). CONCLUSIONS: Opportunities remain in
      timely delivery of a complete HDS to the PCP. Further multifaceted practice
      redesign should be directed at optimizing this critical information transfer
      tool, potentially encompassing electronic medical record utilization and specific
      training for clinicians preparing summaries. Initial efforts should focus on
      ensuring availability of a complete summary (containing items deemed important by
      PCPs including medication list, diagnosis list, and treatment provided) at the
      posthospital follow-up visit.

PMID- 29180551
TI  - Supporting Better Access to Chronic Pain Specialists: The Champlain BASETM
      eConsult Service.
AB  - INTRODUCTION: Excessive wait times for chronic pain are associated with
      significant reductions in quality of life and worse health outcomes. The
      Champlain BASETM (Building Access to Specialists through eConsultation) eConsult
      service can improve access to specialist care for patients with chronic pain by
      facilitating electronic communication between primary care providers (PCPs) and
      specialists. We explored the content of eConsult cases sent to chronic pain
      specialists to identify the major themes emerging from exchanges between PCPs and
      specialists regarding patients with chronic pain. METHODS: We conducted a
      thematic analysis of eConsult cases submitted to chronic pain specialists between
      April 1, 2011 and October 31, 2014, using a constant comparison approach.
      RESULTS: PCPs submitted 128 cases to chronic pain specialists during the study
      period. The study team coded 48 cases before data saturation was reached. PCPs
      sought advice for treating patients with chronic pain arising from a range of
      medical problems, and who frequently struggled with issues of mental health,
      substance dependence, and social complexity. Specialists responded with advice on
      pain management and treatment, directed PCPs to published guidelines and
      community resources, and validated the PCPs' frustration or concerns. Specialists
      provided instruction on safe opioid prescribing and how to identify and manage
      potential cases of substance dependence. CONCLUSION: Providing care to patients
      with chronic pain is a challenge for PCPs, who often experience frustration at
      their inability to provide a definitive solution for patients. Specialists
      offered invaluable feedback not only through guidance and advice, but also with
      sympathy and encouragement.

PMID- 29180552
TI  - Neighborhood Socioeconomic Status and Receipt of Opioid Medication for New Back
      Pain Diagnosis.
AB  - BACKGROUND: Although treatment for new back pain is heavily guideline driven,
      deviations occur frequently. Neighborhood socioeconomic status (nSES) may
      contribute to these deviations. OBJECTIVE: Determine whether nSES is associated
      with type of treatment provided for patients seeking treatment for new back pain
      in primary care clinics. METHODS: This retrospective cohort was conducted in
      academic internal and family medicine practices. Data were examined from the
      Primary Care Patient Data Registry. Eligibility criteria included age >=18 years,
      free of HIV and cancer, and presenting to primary care with a new diagnosis of
      back pain, resulting in1646 patients included. Patients' nSES was determined
      using ZIP code and calculating a validated index of 7 census-tract variables.
      Multinomial logistic regression was used to measure the association between nSES
      and 3 treatment outcomes compared with no pharmacologic management. Outcomes
      included opioid prescription, nonsteroidal anti-inflammatory (NSAID)/muscle
      relaxant prescription, or combined opioid/nonopioid treatment within 90 days of
      initial presentation. Covariates included age, sex, race, high clinic utilization
      (HCU), depression, anxiety, substance use, obesity, comorbidities, smoking,
      number of pain conditions, and physical therapy (PT) referral. RESULTS: The
      cohort was 67.9% female with an average age of 55.72 years (Standard Error [SE] =
      0.387). Compared with no pharmacologic treatment, individuals in the low nSES
      group had 63% higher odds of receiving an opioid only compared with the high nSES
      group (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.01 to 2.62). There
      was no significant association between nSES and odds of nonopioid or combined
      treatment compared with no pharmacotherapy (OR, 1.17; 95% CI, 0.97 to 1.50), (OR,
      1.09; 95% CI, 0.67 to 1.78), respectively. Covariates associated with increased
      odds of opioid only included HCU, ever smoker, and increasing comorbidity index.
      PT referral was associated with NSAID/muscle relaxant only, and increasing age
      and comorbidity index were inversely associated with odds of NSAID/muscle
      relaxant only. Finally, covariates associated with increased odds of receiving
      both therapies included high clinic utilizusation, ever smoking, and PT referral.
      CONCLUSIONS: These data characterize a possible association between low nSES and
      increased risk of receiving an opioid only when being treated for new back pain.
      This may be evidence that patients of low nSES are at increased risk of receiving
      guideline-noncompliant treatment for new back pain.

PMID- 29180553
TI  - Relationship of Opioid Prescriptions to Physical Therapy Referral and
      Participation for Medicaid Patients with New-Onset Low Back Pain.
AB  - INTRODUCTION: Physical therapy (PT) early in the management of low back pain
      (LBP) is associated with reductions in subsequent health care utilization and LBP
      related costs. The objectives of this study were to 1) Examine differences among
      newly consulting patients with LBP who received a PT referral and those who did
      not, 2) examine differences between patients who participated in PT to those who
      did not, and 3) compare the impact of a PT referral and PT participation on LBP
      related health care utilization and costs over 1 year. METHODS: This was a
      retrospective cohort study using electronic medical records and claims data.
      Participants were 454 Medicaid enrollees with new LBP consultations (mean age,
      40.4 years; SD = 12.0; 70% women). Outcomes included advanced imaging,
      injections, emergency department visits, opioid prescriptions, surgery and LBP
      related costs. Variables associated with a PT consult, PT participation, and
      subsequent outcomes were evaluated with multivariate models. RESULTS: A total of
      251 (55%) participants received a PT consult within 7 days of the index LBP visit
      and 81 (19%) participated in PT. The odds of a PT consult were increased if
      patients were prescribed non-steroidal anti-inflammatories (aOR = 1.81; 95%
      confidence interval [CI], 1.0 to 3.27; P = .05) or muscle relaxers (adjusted odds
      ratio [aOR] = 2.24; 95% CI, 1.03 to 4.87; P = .04). Whereas tobacco users and
      individual with multiple comorbidities were less likely to receive a PT consult
      (aOR = 0.52; 95% CI, 0.20 to 0.91) and 0.42 (95% CI, 0.23 to 0.78),
      respectively). Odds of participating in PT were higher for patients receiving an
      radiograph at baseline (odds ratio [OR] = 2.63; 95% CI, 1.25 to 5.53) or having
      multiple comorbidities (OR = 2.96; 95% CI, 1.20 to 7.20). The odds of receiving
      an opioid prescription over the year following the index visit reduced with a PT
      consult (aOR = 0.65; 95% CI, 0.43 to 1.00) and with PT participation (aOR = 0.47;
      95% CI, 0.24 to 0.92). No differences in LBP related costs over 1 year were noted
      between any of the groups. CONCLUSIONS: Among Medicaid recipients with new-onset
      LBP, the index provider's prescription and imaging decisions and patient
      demographics were associated with PT referrals and participation. A referral to
      PT and subsequent PT participation was associated with reduced opioid
      prescriptions during follow-up. There was no difference in overall LBP-related
      health care costs.

PMID- 29180554
TI  - Frequency of Cannabis Use Among Primary Care Patients in Washington State.
AB  - INTRODUCTION: Over 12% of US adults report past-year cannabis use, and among
      those who use daily, 25% or more have a cannabis use disorder. Use is increasing
      as legal access expands. Yet, cannabis use is not routinely assessed in primary
      care, and little is known about use among primary care patients and relevant
      demographic and behavioral health subgroups. This study describes the prevalence
      and frequency of past-year cannabis use among primary care patients assessed for
      use during a primary care visit. METHODS: This observational cohort study
      included adults who made a visit to primary care clinics with annual behavioral
      health screening, including a single-item question about frequency past-year
      cannabis use (March 2015 to February 2016; n = 29,857). Depression, alcohol and
      other drug use were also assessed by behavioral health screening. Screening
      results, tobacco use, and diagnoses for past-year behavioral health conditions
      (e.g., mental health and substance use disorders) were obtained from EHRs.
      RESULTS: Among patients who completed the cannabis use question (n = 22,095; 74%
      of eligible patients), 15.3% (14.8% to 15.8%) reported any past-year use: 12.2%
      (11.8% to 12.6%) less than daily, and 3.1% (2.9%-3.3%) daily. Among 2228 patients
      age 18 to 29 years, 36.0% (34.0% to 38.0%) reported any cannabis use and 8.1%
      (7.0% to 9.3%) daily use. Daily cannabis use was common among men age 18 to 29
      years who used tobacco or screened positive for depression or used tobacco: 25.5%
      (18.8% to 32.1%) and 31.7% (23.3% to 40.0%), respectively. CONCLUSIONS: Cannabis
      use was common in adult primary care patients, especially among younger patients
      and those with behavioral health conditions. Results highlight the need for
      primary care approaches to address cannabis use.

PMID- 29180555
TI  - The Diagnostic Value of the Patient's Reason for Encounter for Diagnosing Cancer
      in Primary Care.
AB  - PURPOSE: Family physicians (FPs) have to recognize alarm symptoms and estimate
      the probability of cancer to manage these symptoms correctly. Mostly, patients
      start the consultation with a spontaneous statement on why they visit the doctor.
      This is also called the reason for encounter (RFE). It precedes the interaction
      and interpretation by FPs and patients. The aim of this study is to investigate
      the predictive value of alarm symptoms as the RFE for diagnosing cancer in
      primary care. DESIGN AND SETTING: Retrospective cohort study in a Dutch practice
      based research network (Family Medicine Network). METHOD: We analyzed all
      patients >45 years of age listed in the practice-based research network, FaMe
      net, in the period 1995 to 2014 (118.219 patient years). We focused on a
      selection of alarm symptoms as defined by the Dutch Cancer Society and Cancer
      Research UK. We calculated the positive predictive value (PPV) of alarm symptoms,
      spontaneously mentioned in the beginning of the consultation by the patient
      (RFE), for diagnosing cancer. RESULTS: The highest PPVs were found for patients
      spontaneously mentioning a breast lump (PPV 14.8%), postmenopausal bleeding (PPV
      3.9%), hemoptysis (PPV 2.7%), rectal bleeding (PPV 2.6%), hematuria (PPV 2.2%)
      and change in bowel movements (PPV 1.8%). CONCLUSION: Patients think about going
      to their physician and think about their first uttered statements during the
      consultation. In the case of cancer, the diagnostic workup during the
      consultation on alarm symptoms will add to the predictive value of these reasons
      for encounter. However, it is important to realize that the statement made by the
      patient entering the consultation room has a significant predictive value in
      itself.

PMID- 29180556
TI  - Older Adults' Preferences for When and How to Discuss Life Expectancy in Primary
      Care.
AB  - INTRODUCTION: Life expectancy is important to inform a number of clinical
      decisions in primary care but its communication is challenging for clinicians.
      METHODS: This qualitative interview study with 40 community-dwelling older adults
      explored their perspectives on how and when to discuss life expectancy in primary
      care. RESULTS: Most participants did not want to discuss life expectancy longer
      than 1 year but were open to being offered discussion by clinicians. Suggestions
      included using health decline as trigger for discussion and discussing with
      family members instead of patient. DISCUSSION: Although older adults have varied
      preferences for the timing and content of life expectancy discussions in primary
      care, it was generally acceptable for clinicians to offer the opportunity for
      this type of discussion.

PMID- 29180558
TI  - Using Drug Prescribing Patterns to Identify Stewards of Cost-Conscious Care.
AB  - PURPOSE: To characterize family physicians (FPs) who are stewards of care by
      consistently prescribing omeprazole over esomeprazole. METHODS: Cross-sectional
      analysis of physicians prescribing omeprazole or esomeprazole under Medicare Part
      D in 2014. RESULTS: There was a regional trend with 49% of Western FPs but only
      6% of Southern FPs rarely prescribing esomeprazole. Physicians had increased odds
      of being a steward if they worked with a care coordinator (P < .001), at a
      patient-centered medical home (P < .001), or in a large practice (P < .001).
      CONCLUSIONS: If these findings are replicated across multiple drugs, future
      outreach could be conducted based on provider prescribing patterns.

PMID- 29180557
TI  - Worsening Rural-Urban Gap in Hospital Mortality.
AB  - BACKGROUND: One out of every 5 Americans live in rural communities. Rural
      Americans have higher rates of early and preventable deaths outside of the
      hospital than their urban counterparts. How rurality relates to hospital
      mortality is unknown. We sought to determine the association between rural versus
      urban residence and hospital mortality. METHODS: This is a retrospective
      observational study of 4,412,942 nonmaternal, nonneonatal hospitalizations in
      2008, and 3899,464 nonmaternal, nonneonatal hospitalizations in 2013 using all
      payer, all-age data from the National Inpatient Sample of the Health care Cost
      and Utilization Project. Using multivariable logistic regression, we report the
      association between rural versus urban location of residence and hospital
      mortality, adjusting for chronic disease burden, age, income, and insurance
      status. RESULTS: The unadjusted probability of hospital mortality for urban
      patients decreased from 2.51% (95% CI, 2.40 to 2.62) in 2008 to 2.27% (95% CI,
      2.22 to 2.32) in 2013 (P < .001). Hospital mortality did not change for rural
      patients over this same time period (2008: 2.66% [95% CI, 2.57 to 2.74], 2013:
      2.66% [95% CI, 2.60 to 2.72]; P = .99). Adjusting for covariates accounted for
      the rural-urban hospital mortality difference in 2008 (rural: 2.13% [95% CI, 2.05
      to 2.21], urban: 2.11% [95% CI, 2.02 to 2.20]; P = .67), but did not fully
      explain the difference in 2013 (rural: 1.92% [95% CI, 1.87 to 1.97]; urban: 1.76%
      [95% CI, 1.72 to 1.80], P < .001), resulting in 8416 excess deaths among
      hospitalized patients from rural areas. CONCLUSION AND RELEVANCE: In 2013,
      patients living in rural areas of the United States had a greater probability of
      hospital mortality than their urban counterparts. Explaining excess rural
      hospital deaths will require further attention to the patient, community, and
      health system factors that distinguish rural from urban populations.

PMID- 29180559
TI  - Predicting Risk for Opioid Misuse in Chronic Pain with a Single-Item Measure of
      Catastrophic Thinking.
AB  - BACKGROUND: Chronic pain patients are frequently treated with opioid medications
      in primary care, where brief measures of risk for opioid misuse have great
      utility. Catastrophic thinking is a clinically relevant and potentially
      modifiable factor associated with several chronic pain outcomes, including risk
      for opioid misuse. This study examined the utility of a single-item measure of
      pain-related catastrophizing in predicting risk of opioid misuse. METHOD: 119
      chronic pain patients completed the Coping Strategies Questionnaire
      catastrophizing item, Pain Catastrophizing Scale (PCS), and Screener and Opioid
      Assessment for Patients with Pain-Revised (SOAPP-R). Area under the receiver
      operator curve (AUC) and linear regression were used to examine predictive
      utility of the catastrophizing item. RESULTS: The catastrophizing item
      demonstrated a fair ability to discriminate those with high risk for opioid
      misuse on the SOAPP-R (AUC = 0.74), whereas the PCS demonstrated good
      discrimination (AUC = 0.85). The single item alone accounted for 30% of variance
      in SOAPP-R scores. CONCLUSION: A single question assessing pain catastrophizing
      has utility for predicting risk for opioid misuse. In addition, it provides the
      primary care provider with information on a potentially modifiable risk factor
      that can be addressed within the context of a brief clinical visit.

PMID- 29180560
TI  - Dysrhythmias with Loperamide Used for Opioid Withdrawal.
AB  - The antidiarrheal loperamide has had a recent, drastic increase in off-label use
      as an alternative treatment for symptoms of opioid withdrawal. The concept of
      this is easily discovered on the Internet and social media, where there are
      multiple blogs and forums promoting loperamide use at doses of 70 to 200 mg per
      day. Unfortunately, the serious side effects are not well recognized. Multiple
      cases of cardiac dysrhythmias contributing to death have been highlighted in
      recent literature. In November 2016, the US Food & Drug Administration released a
      statement highlighting the potential heart effects and risk of death with high
      doses of loperamide.1 This case regards a 22-year-old who took 200 mg of
      loperamide per day for 2 years as an alternative to methadone in her attempts to
      wean off heroin. Her subsequent spontaneous collapse, dysrhythmias, and acute
      hospital treatment are reviewed in detail as they were contradictory to standard
      therapy and required a multidisciplinary approach. Her outpatient management
      addressed the complex biological, psychological, and social aspects of her
      addiction.

PMID- 29180561
TI  - Notalgia Paresthetica Relieved by Cervical Traction.
AB  - Notalgia paresthetica is a syndrome of unilateral, chronic pruritis that is
      associated with burning pain, paresthesia, numbness, and hyperesthesia localized
      to the medial and inferior scapula. The condition does not respond to anti
      inflammatory drugs or traditional antipruritic agents and has variable responses
      to numerous other reported pharmacologic and nonpharmacologic therapies. Although
      the etiology is thought to be nerve impingement, neurologic and musculoskeletal
      causes are often not considered in the differential diagnosis. We present a
      report of a woman with a 2-year history of refractory notalgia paresthetica.
      Based on spinal imaging showing cervical neuroforaminal stenosis, the patient was
      prescribed a course of cervical traction. Her symptoms resolved and have not
      returned after 2 years of followup. We believe this is the first case report of
      successful treatment of notalgia paresthetica with cervical traction.

PMID- 29180562
TI  - The Single Graduate Medical Education (GME) Accreditation System Will Change the
      Future of the Family Medicine Workforce.
AB  - BACKGROUND: Due to the Accreditation Council for Graduate Medical Education
      (ACGME)/American Osteopathic Association (AOA) single-accreditation model, the
      specialty of family medicine may see as many as 150 programs and 500 trainees in
      AOA-accredited programs seek ACGME accreditation. This analysis serves to better
      understand the composition of physicians completing family medicine residency
      training and their subsequent certification by the American Board of Family
      Medicine. METHODS: We identified residents who completed an ACGME-accredited or
      dual-accredited family medicine residency program between 2006 and 2016 and cross
      tabulated the data by graduation year and by educational background (US Medical
      Graduate-MD [USMG-MD], USMG-DO, or International Medical Graduate-MD [IMG-MD]) to
      examine the cohort composition trend over time. RESULTS: The number and
      proportion of osteopaths completing family medicine residency training continues
      to rise concurrent with a decline in the number and proportion of IMGs. Take
      Rates for USMG-MDs and USMG-IMGs seem stable; however, the Take Rate for the USMG
      DOs has generally been rising since 2011. CONCLUSIONS: There is a clear change in
      the composition of graduating trainees entering the family medicine workforce. As
      the transition to a single accreditation system for graduate medical education
      progresses, further shifts in the composition of this workforce should be
      expected.

PMID- 29180563
TI  - Strategies for Increasing the Role of Family Medicine in Mexican Health Care
      Reform.
AB  - There is little or no role for primary care and family medicine in current health
      reforms in Mexico. However, robust evidence shows that primary care helps prevent
      morbidity and mortality and increases health equity. Mexico has participated in
      several international meetings sponsored by the World Organization of National
      Colleges, Academies and Academic Associations and the North American Primary Care
      Research Group that are aimed at increased understanding of national health
      systems and the need to strengthen primary care for improved health outcomes.
      From 1 of these meetings the Cancun Manifesto emerged, with a strategic plan to
      increase the stature and impact of the Mexican College of Family Physicians
      (COLMEXAC) in strengthening primary care in Mexico. We aim to describe this
      strategic plan and discuss its early implementation, and for this account to
      serve as a possible formula for other countries. The 5 specific strategies
      discussed are 1) the need for consensus on the leading role of the Mexican family
      physician in the national health system; 2) health ecology research; 3) to
      improve the perception of patients about the benefits of primary care and family
      medicine; 4) to organize meetings of health providers, users, and other
      stakeholders; and 5) to promote the professionalization of COLMEXAC as a legal
      entity.

PMID- 29180564
TI  - Re: Patient Beliefs Have a Greater Impact Than Barriers on Medication Adherence
      in a Community Health Center.

PMID- 29180567
TI  - Uhrf1 is indispensable for normal limb growth by regulating chondrocyte
      differentiation through specific gene expression.
AB  - Transcriptional regulation can be tightly orchestrated by epigenetic regulators.
      Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is
      reported to have diverse epigenetic functions, including regulation of DNA
      methylation. However, the physiological functions of Uhrf1 in skeletal tissues
      remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1
      conditional knockout mice (Uhrf1DeltaLimb/DeltaLimb ) exhibit remarkably
      shortened long bones that have morphological deformities due to dysregulated
      chondrocyte differentiation and proliferation. RNA-seq performed on primary
      cultured chondrocytes obtained from Uhrf1DeltaLimb/DeltaLimb mice showed abnormal
      chondrocyte differentiation. In addition, integrative analyses using RNA-seq and
      MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and
      increased gene expression through reduced DNA methylation in the promoter regions
      of 28 genes, including Hspb1, which is reported to be an IL1-related gene and to
      affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can
      normalize abnormal expression of genes involved in chondrocyte differentiation,
      such as Mmp13 These results indicate that Uhrf1 governs cell type-specific
      transcriptional regulation by controlling the genome-wide DNA methylation status
      and regulating consequent cell differentiation and skeletal maturation.

PMID- 29180568
TI  - Maternal Nanog is required for zebrafish embryo architecture and for cell
      viability during gastrulation.
AB  - Nanog has been implicated in establishment of pluripotency in mammals and in
      zygotic genome activation in zebrafish. In this study, we characterize the
      development of MZnanog (maternal and zygotic null) mutant zebrafish embryos.
      Without functional Nanog, epiboly is severely affected, embryo axes do not form
      and massive cell death starts at the end of gastrulation. We show that three
      independent defects in MZnanog mutants contribute to epiboly failure: yolk
      microtubule organization required for epiboly is abnormal, maternal mRNA fails to
      degrade owing to the absence of miR-430, and actin structure of the yolk
      syncytial layer does not form properly. We further demonstrate that the cell
      death in MZnanog embryos is cell-autonomous. Nanog is necessary for correct
      spatial expression of the ventral-specifying genes bmp2b, vox and vent, and the
      neural transcription factor her3 It is also required for the correctly timed
      activation of endoderm genes and for the degradation of maternal eomesa mRNA via
      miR-430. Our findings suggest that maternal Nanog coordinates several gene
      regulatory networks that shape the embryo during gastrulation.

PMID- 29180570
TI  - Perturbation of canonical and non-canonical BMP signaling affects migration,
      polarity and dendritogenesis of mouse cortical neurons.
AB  - Bone morphogenetic protein (BMP) signaling has been implicated in the regulation
      of patterning of the forebrain and as a regulator of neurogenesis and gliogenesis
      in the mammalian cortex. However, its role in other aspects of cortical
      development in vivo remains unexplored. We hypothesized that BMP signaling might
      regulate additional processes during the development of cortical neurons after
      observing active BMP signaling in a spatiotemporally dynamic pattern in the mouse
      cortex. Our investigation revealed that BMP signaling specifically regulates the
      migration, polarity and the dendritic morphology of upper layer cortical neurons
      born at E15.5. On further dissection of the role of canonical and non-canonical
      BMP signaling in each of these processes, we found that migration of these
      neurons is regulated by both pathways. Their polarity, however, appears to be
      affected more strongly by canonical BMP signaling, whereas dendritic branch
      formation appears to be somewhat more strongly affected by LIMK-mediated non
      canonical BMP signaling.

PMID- 29180569
TI  - The skeletal phenotype of achondrogenesis type 1A is caused exclusively by
      cartilage defects.
AB  - Inactivating mutations in the ubiquitously expressed membrane trafficking
      component GMAP-210 (encoded by Trip11) cause achondrogenesis type 1A (ACG1A).
      ACG1A is surprisingly tissue specific, mainly affecting cartilage development.
      Bone development is also abnormal, but as chondrogenesis and osteogenesis are
      closely coupled, this could be a secondary consequence of the cartilage defect. A
      possible explanation for the tissue specificity of ACG1A is that cartilage and
      bone are highly secretory tissues with a high use of the membrane trafficking
      machinery. The perinatal lethality of ACG1A prevents investigating this
      hypothesis. We therefore generated mice with conditional Trip11 knockout alleles
      and inactivated Trip11 in chondrocytes, osteoblasts, osteoclasts and pancreas
      acinar cells, all highly secretory cell types. We discovered that the ACG1A
      skeletal phenotype is solely due to absence of GMAP-210 in chondrocytes. Mice
      lacking GMAP-210 in osteoblasts, osteoclasts and acinar cells were normal. When
      we inactivated Trip11 in primary chondrocyte cultures, GMAP-210 deficiency
      affected trafficking of a subset of chondrocyte-expressed proteins rather than
      globally impairing membrane trafficking. Thus, GMAP-210 is essential for
      trafficking specific cargoes in chondrocytes but is dispensable in other highly
      secretory cells.

PMID- 29180571
TI  - The primary role of zebrafish nanog is in extra-embryonic tissue.
AB  - The role of the zebrafish transcription factor Nanog has been controversial. It
      has been suggested that Nanog is primarily required for the proper formation of
      the extra-embryonic yolk syncytial layer (YSL) and only indirectly regulates gene
      expression in embryonic cells. In an alternative scenario, Nanog has been
      proposed to directly regulate transcription in embryonic cells during zygotic
      genome activation. To clarify the roles of Nanog, we performed a detailed
      analysis of zebrafish nanog mutants. Whereas zygotic nanog mutants survive to
      adulthood, maternal-zygotic (MZnanog) and maternal mutants exhibit developmental
      arrest at the blastula stage. In the absence of Nanog, YSL formation and epiboly
      are abnormal, embryonic tissue detaches from the yolk, and the expression of
      dozens of YSL and embryonic genes is reduced. Epiboly defects can be rescued by
      generating chimeric embryos of MZnanog embryonic tissue with wild-type vegetal
      tissue that includes the YSL and yolk cell. Notably, cells lacking Nanog readily
      respond to Nodal signals and when transplanted into wild-type hosts proliferate
      and contribute to embryonic tissues and adult organs from all germ layers. These
      results indicate that zebrafish Nanog is necessary for proper YSL development but
      is not directly required for embryonic cell differentiation.

PMID- 29180572
TI  - The ATPase activity of Asna1/TRC40 is required for pancreatic progenitor cell
      survival.
AB  - Asna1, also known as TRC40, is implicated in the delivery of tail-anchored (TA)
      proteins into the endoplasmic reticulum (ER), in vesicle-mediated transport, and
      in chaperoning unfolded proteins during oxidative stress/ATP depletion. Here, we
      show that Asna1 inactivation in pancreatic progenitor cells leads to
      redistribution of the Golgi TA SNARE proteins syntaxin 5 and syntaxin 6, Golgi
      fragmentation, and accumulation of cytosolic p62+ puncta. Asna1-/- multipotent
      progenitor cells (MPCs) selectively activate integrated stress response signaling
      and undergo apoptosis, thereby disrupting endocrine and acinar cell
      differentiation, resulting in pancreatic agenesis. Rescue experiments implicate
      the Asna1 ATPase activity and a CXXC di-cysteine motif in ensuring Golgi
      integrity, syntaxin 5 localization and MPC survival. Ex vivo inhibition of
      retrograde transport reproduces the perturbed Golgi morphology, and syntaxin 5
      and syntaxin 6 expression, whereas modulation of p53 activity, using PFT-alpha
      and Nutlin-3, prevents or reproduces apoptosis in Asna1-deficient and wild-type
      MPCs, respectively. These findings support a role for the Asna1 ATPase activity
      in ensuring the survival of pancreatic MPCs, possibly by counteracting p53
      mediated apoptosis.

PMID- 29180574
TI  - miR-126-5p promotes retinal endothelial cell survival through SetD5 regulation in
      neurons.
AB  - MicroRNAs are key regulators of angiogenesis, as illustrated by the vascular
      defects observed in miR-126-deficient animals. The miR-126 duplex gives rise to
      two mature microRNAs (miR-126-3p and -5p). The vascular defects in these mutant
      animals were attributed to the loss of miR-126-3p but the role of miR-126-5p
      during normal angiogenesis in vivo remains unknown. Here, we show that miR-126-5p
      is expressed in endothelial cells but also by retinal ganglion cells (RGCs) of
      the mouse postnatal retina and participates in protecting endothelial cells from
      apoptosis during the establishment of the retinal vasculature. miR-126-5p
      negatively controls class 3 semaphorin protein (Sema3A) in RGCs through the
      repression of SetD5, an uncharacterized member of the methyltransferase family of
      proteins. In vitro, SetD5 controls Sema3A expression independently of its SET
      domain and co-immunoprecipitates with BRD2, a bromodomain protein that recruits
      transcription regulators onto the chromatin. Both SetD5 and BRD2 bind to the
      transcription start site and to upstream promoter regions of the Sema3a locus and
      BRD2 is necessary for the regulation of Sema3A expression by SetD5. Thus,
      neuronally expressed miR-126-5p regulates angiogenesis by protecting endothelial
      cells of the developing retinal vasculature from apoptosis.

PMID- 29180575
TI  - Radiation-induced spinal nerve root cavernous malformations as a rare cause of
      radiculopathy.

PMID- 29180576
TI  - Editors' Note.

PMID- 29180573
TI  - Plasticity within the niche ensures the maintenance of a Sox2+ stem cell
      population in the mouse incisor.
AB  - In mice, the incisors grow throughout the animal's life, and this continuous
      renewal is driven by dental epithelial and mesenchymal stem cells. Sox2 is a
      principal marker of the epithelial stem cells that reside in the mouse incisor
      stem cell niche, called the labial cervical loop, but relatively little is known
      about the role of the Sox2+ stem cell population. In this study, we show that
      conditional deletion of Sox2 in the embryonic incisor epithelium leads to growth
      defects and impairment of ameloblast lineage commitment. Deletion of Sox2
      specifically in Sox2+ cells during incisor renewal revealed cellular plasticity
      that leads to the relatively rapid restoration of a Sox2-expressing cell
      population. Furthermore, we show that Lgr5-expressing cells are a subpopulation
      of dental Sox2+ cells that also arise from Sox2+ cells during tooth formation.
      Finally, we show that the embryonic and adult Sox2+ populations are regulated by
      distinct signalling pathways, which is reflected in their distinct transcriptomic
      signatures. Together, our findings demonstrate that a Sox2+ stem cell population
      can be regenerated from Sox2- cells, reinforcing its importance for incisor
      homeostasis.

PMID- 29180577
TI  - Letter Re: Practice guideline summary: Reducing brain injury following
      cardiopulmonary resuscitation: Report of the Guideline Development,
      Dissemination, and Implementation Subcommittee of the American Academy of
      Neurology.

PMID- 29180578
TI  - Letter Re: Practice guideline summary: Reducing brain injury following
      cardiopulmonary resuscitation: Report of the Guideline Development,
      Dissemination, and Implementation Subcommittee of the American Academy of
      Neurology.

PMID- 29180579
TI  - Author response: Practice guideline summary: Reducing brain injury following
      cardiopulmonary resuscitation: Report of the Guideline Development,
      Dissemination, and Implementation Subcommittee of the American Academy of
      Neurology.

PMID- 29180580
TI  - Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis
      clinical trials.

PMID- 29180581
TI  - Mystery Case: A 61-year-old woman with lower extremity paralysis and sensory
      loss.

PMID- 29180583
TI  - How comorbid conditions affect the choice of treatment in multiple sclerosis.

PMID- 29180582
TI  - Teaching NeuroImages: Brain imaging findings in acute methanol toxicity.

PMID- 29180584
TI  - Margaret McCartney: Let's have a report on what resources the NHS needs.

PMID- 29180585
TI  - A trivalent HCV vaccine elicits broad and synergistic polyclonal antibody
      response in mice and rhesus monkey.
AB  - OBJECTIVE: Despite the development of highly effective direct-acting antivirals,
      a prophylactic vaccine is needed for eradicating HCV. A major hurdle of HCV
      vaccine development is to induce immunity against HCV with high genome diversity.
      We previously demonstrated that a soluble E2 (sE2) expressed from insect cells
      induces broadly neutralising antibodies (NAbs) and prevents HCV infection. The
      objective of this study is to develop a multivalent HCV vaccine to increase the
      antigenic coverage. DESIGN: We designed a trivalent vaccine containing sE2 from
      genotype 1a, 1b and 3a. Mice and rhesus macaques were immunised with monovalent
      or trivalent sE2 vaccine, and sera or purified immunoglobulin were assessed for
      neutralisation against a panel of cell culture-derived virion (HCVcc) of genotype
      1-7 in cell culture. Splenocytes from the vaccinated macaques were assessed for
      HCV-specific T cell response. RESULTS: We showed that the trivalent vaccine
      elicited pangenotypic NAbs in mice, which neutralised HCVcc of all the seven
      genotypes more potently than the monovalent vaccine. Further analyses
      demonstrated that each sE2 component of this trivalent vaccine elicited unique
      spectrum of NAbs which acted synergistically to inhibit HCV infection. Finally,
      the trivalent vaccine triggered stronger and more uniform multigenotypic
      neutralising antibody response than the monovalent vaccine in rhesus macaques.
      CONCLUSIONS: In summary, we developed a trivalent HCV vaccine that induces broad
      and synergistic-acting neutralising antibodies in mice and non-human primates.

PMID- 29180587
TI  - Correction to: Letter by Tang et al Regarding Article, "General Anesthesia Versus
      Conscious Sedation for Endovascular Treatment of Acute Ischemic Stroke: The
      Anstroke Trial (Anesthesia During Stroke)".

PMID- 29180588
TI  - Correction to: Stratifying Stroke Risk in Atrial Fibrillation: Beyond Clinical
      Risk Scores.

PMID- 29180589
TI  - Correction to: Guidelines for Adult Stroke Rehabilitation and Recovery: A
      Guideline for Healthcare Professionals From the American Heart
      Association/American Stroke Association.

PMID- 29180590
TI  - Examining tRNA 3'-ends in Escherichia coli: teamwork between CCA-adding enzyme,
      RNase T, and RNase R.
AB  - tRNA maturation and quality control are crucial for proper functioning of these
      transcripts in translation. In several organisms, defective tRNAs were shown to
      be tagged by poly(A) or CCACCA tails and subsequently degraded by 3'
      exonucleases. In a deep-sequencing analysis of tRNA 3'-ends, we detected the
      CCACCA tag also in Escherichia coli However, this tag closely resembles several
      3'-trailers of tRNA precursors targeted for maturation and not for degradation.
      Here, we investigate the ability of two important exonucleases, RNase R and RNase
      T, to distinguish tRNA precursors with a native 3'-trailer from tRNAs with a
      CCACCA tag. Our results show that the degrading enzyme RNase R breaks down both
      tRNAs primed for degradation as well as precursor transcripts, indicating that it
      is a rather nonspecific RNase. RNase T, a main processing exonuclease involved in
      trimming of 3'-trailers, is very inefficient in converting the CCACCA-tagged tRNA
      into a mature transcript. Hence, while both RNases compete for trailer-containing
      tRNA precursors, the inability of RNase T to process CCACCA tails ensures that
      defective tRNAs cannot reenter the functional tRNA pool, representing a safeguard
      to avoid detrimental effects of tRNAs with erroneous integrity on protein
      synthesis. Furthermore, these data indicate that the RNase T-mediated end
      turnover of the CCA sequence represents a means to deliver a tRNA to a repeated
      quality control performed by the CCA-adding enzyme. Hence, originally described
      as a futile side reaction, the tRNA end turnover seems to fulfill an important
      function in the maintenance of the tRNA pool in the cell.

PMID- 29180591
TI  - Developing outcome measures assessing wound management and patient experience: a
      mixed methods study.
AB  - OBJECTIVES: To develop outcome measures to assess practical management of primary
      surgical wounds and patient experience. DESIGN: Mixed methods, including
      qualitative interviews and data extraction from published randomised controlled
      trials (RCTs). SETTING: Two university-teaching NHS hospitals and three district
      NHS hospitals in the South West and Midlands regions of England. PARTICIPANTS:
      Sixty-four patients and 15 healthcare professionals from abdominal general
      surgical specialities and obstetrics (caesarean section). METHODS: Measures were
      developed according to standard guidelines to identify issues relevant to
      patients' experiences of surgical wounds and dressings, including analysis of
      existing RCT outcomes and semi-structured interviews. These were written into
      provisional questionnaire items for a single outcome measure. Cognitive
      interviews with patients and healthcare professionals assessed face validity,
      acceptability and relevance. Findings from interviews were regularly shared with
      the study team who suggested amendments to modify and reword items to improve
      understanding before further iterative testing with patients and healthcare
      professionals. RESULTS: Analyses of existing RCT outcomes and interviews produced
      a total of 69 issues. Pretesting and iterative revision established the need for
      two separate measures. One measure addresses healthcare professionals' experience
      of wound management in two key areas: exudate and its impact, and allergic
      reactions to the dressing. The other measure addresses patients' experience of
      wounds in seven key areas: wound comfort, dressing removal, dressings to protect
      the wound, impact on daily activities, ease of movement, anxiety about the wound
      and satisfaction with dressing. Each measure took less than five min to complete
      and both were understood and acceptable to patients and healthcare professionals.
      CONCLUSION: This in-depth study has developed two measures to assess practical
      management of primary surgical wounds and patient experience. Further work to
      test their validity, reliability and application to other settings is now
      required. TRIAL REGISTRATION NUMBER: HTA - 12/200/04; Pre-results.

PMID- 29180592
TI  - Cost-effectiveness of a preferred intensity exercise programme for young people
      with depression compared with treatment as usual: an economic evaluation
      alongside a clinical trial in the UK.
AB  - OBJECTIVES: To assess the cost-effectiveness of preferred intensity exercise
      programme for young people with depression compared with a treatment as usual
      control group. DESIGN: A 'within trial' cost-effectiveness and cost-utility
      analysis conducted alongside a randomised controlled trial. The perspective of
      the analysis was the UK National Health Service and social services. SETTING: The
      intervention was provided in a community leisure centre setting. PARTICIPANTS: 86
      young people aged 14-17 years attending Tier 2 and Tier 3 CAMHS (Child and
      Adolescent Mental Health Services) outpatient services presenting with
      depression. INTERVENTIONS: The intervention comprised 12 separate sessions of
      circuit training over a 6-week period. Sessions were supervised by a qualified
      exercise therapist. Participants also received treatment as usual. The comparator
      group received treatment as usual. RESULTS: We found improvements in the
      Children's Depression Inventory-2 (CDI-2) and estimated cost-effectiveness at L61
      per point improvement in CDI-2 for the exercise group compared with control. We
      found no evidence that the exercise intervention led to differences in quality
      adjusted life years (QALY). QALYs were estimated using the EQ-5D-5L (5-level
      version of EuroQol-5 dimension). CONCLUSIONS: There is evidence that exercise can
      be an effective intervention for adolescents with depression and the current
      study shows that preferred intensity exercise could also represent a cost
      effective intervention in terms of the CDI-2. TRIAL REGISTRATION NUMBER:
      NCT01474837.

PMID- 29180593
TI  - Qualitative interview study of antibiotics and self-management strategies for
      respiratory infections in primary care.
AB  - OBJECTIVE: To explore perceptions of illness, the decisions to consult and the
      acceptability of delayed antibiotic prescriptions and self-help treatments for
      respiratory tract infections (RTIs). DESIGN: Qualitative semistructured interview
      study. SETTING: UK primary care. PARTICIPANTS: 20 adult patients who had been
      participating in the 'PIPS' (Pragmatic Ibuprofen Paracetamol and Steam) trial in
      the South of England. METHOD: Semistructured telephone interviews were conducted
      with participants to explore their experiences and views on various treatments
      for RTI. RESULTS: Participants had concerns about symptoms that were not
      clinically serious and were mostly unaware of the natural history of RTIs, but
      were aware of the limitations of antibiotics and did not expect them with every
      consultation. Most viewed delayed prescriptions positively and had no strong
      preference over which technique is used to deliver the delayed antibiotic, but
      some patients received mixed messages, such as being told their infection was
      viral then being given an antibiotic, or were sceptical about the rationale.
      Participants disliked self-help treatments that involved taking medication and
      were particularly concerned about painkillers in combination. Steam inhalation
      was viewed as only moderately helpful for mild symptoms. CONCLUSION: Delayed
      prescribing is acceptable no matter how the delay is operationalised, but
      explanation of the rationale is needed and care taken to minimise mixed messages
      about the severity of illnesses and causation by viruses or bacteria. Better
      access is needed to good natural history information, and the signs and symptoms
      requiring or not requiring general practitioner advice. Significant concerns
      about paracetamol, ibuprofen and steam inhalation are likely to need careful
      exploration in the consultation.

PMID- 29180594
TI  - Referrers' point of view on the referral process to neurosurgery and opinions on
      neurosurgeons: a large-scale regional survey in the UK.
AB  - OBJECTIVES: There is an increased reliance on online referral systems (ORS)
      within neurosurgical departments across the UK. Opinions of neurosurgeons on ORS
      are extensively reported but those of referrers have hardly been sought. Our
      study aims at ascertaining our referring colleagues' views on our ORS and its
      impact on patient care, their opinions on neurosurgeons and how to improve our
      referral process. SETTING: 14 district general hospitals and one teaching
      hospital. PARTICIPANTS: 641 healthcare professionals across a range of medical
      and surgical specialties including doctors of all grades, nurses and
      physiotherapists. Survey responses were obtained by medical students using a
      smartphone application. RESULTS: Although 92% of respondents were aware of the
      ORS, 74% would routinely phone the on-call registrar either before or after
      making referrals online. The majority (44%) believed their call to relate to a
      life-threatening emergency. 62% of referrers considered the ORS helpful in
      informing patients' care and 48% had a positive opinion of their interaction with
      neurosurgical registrars. On ways to improve the ORS, 50% selected email/text
      confirmation of response sent to referrers and 16% to referring consultants.
      CONCLUSION: Our results confirm that referrers feel that using our ORS positively
      impacts patient care but that it remains in need of improvement in order to
      better suit our colleagues' needs when it comes to managing neurosurgical
      patients. We feel that the promotion of neurosurgical education and mitigation of
      the effects of adverse workplace human factors are likely to achieve the common
      goal of neurosurgeons and referrers alike: a high standard in patient care.

PMID- 29180595
TI  - ALKBH10B Is an RNA N6-Methyladenosine Demethylase Affecting Arabidopsis Floral
      Transition.
AB  - N6-methyladenosine (m6A) is the most abundant, internal, posttranscriptional
      modification in mRNA among all higher eukaryotes. In mammals, this modification
      is reversible and plays broad roles in the regulation of mRNA metabolism and
      processing. Despite its importance, previous studies on the role and mechanism of
      m6A methylation in Arabidopsis thaliana have been limited. Here, we report that
      ALKBH10B is a demethylase that oxidatively reverses m6A methylation in mRNA in
      vitro and in vivo. Depletion of ALKBH10B in the alkbh10b mutant delays flowering
      and represses vegetative growth. Complementation with wild-type ALKBH10B, but not
      a catalytically inactive mutant (ALKBH10B H366A/E368A), rescues these effects in
      alkbh10b-1 mutant plants, suggesting the observed phenotypes are controlled by
      the catalytic action of ALKBH10B We show that ALKBH10B-mediated mRNA
      demethylation affects the stability of target transcripts, thereby influencing
      floral transition. We identified 1190 m6A hypermethylated transcripts in the
      alkbh10b-1 mutant involved in plant development. The discovery and
      characterization of the archetypical RNA demethylase in Arabidopsis sheds light
      on the occurrence and functional role(s) of reversible mRNA methylation in plants
      and defines the role of m6A RNA modification in Arabidopsis floral transition.

PMID- 29180597
TI  - Open-Source Device Tracks Mechanical Properties of Living Plant Cells in 3D.

PMID- 29180596
TI  - Patterns and Consequences of Subgenome Differentiation Provide Insights into the
      Nature of Paleopolyploidy in Plants.
AB  - Polyploidy is an important feature of plant genomes, but the nature of many
      polyploidization events remains to be elucidated. Here, we demonstrate that the
      evolutionary fates of the subgenomes in maize (Zea mays) and soybean (Glycine
      max) have followed different trajectories. One subgenome has been subject to
      relaxed selection, lower levels of gene expression, higher rates of transposable
      element accumulation, more small interfering RNAs and DNA methylation around
      genes, and higher rates of gene loss in maize, whereas none of these features
      were observed in soybean. Nevertheless, individual gene pairs exhibit
      differentiation with respect to these features in both species. In addition, we
      observed a higher number of chromosomal rearrangements and higher frequency of
      retention of duplicated genes in soybean than in maize. Furthermore, soybean
      "singletons" were found to be more frequently tandemly duplicated than
      "duplicates" in soybean, which may, to some extent, counteract the genome
      imbalance caused by gene loss. We propose that unlike in maize, in which two
      subgenomes were distinct prior to the allotetraploidization event and thus
      experienced global differences in selective constraints, in soybean, the two
      subgenomes were far less distinct prior to polyploidization, such that individual
      gene pairs, rather than subgenomes, experienced stochastic differences over
      longer periods of time, resulting in retention of the majority of duplicates.

PMID- 29180599
TI  - Too hard to swallow: a secret secondary defence of an aposematic insect.
AB  - Anti-predator strategies are significant components of adaptation in prey
      species. Aposematic prey are expected to possess effective defences that have
      evolved simultaneously with their warning colours. This study tested the
      hypothesis of the defensive function and ecological significance of the hard body
      in aposematic Pachyrhynchus weevils pioneered by Alfred Russel Wallace nearly 150
      years ago. We used predation trials with Japalura tree lizards to assess the
      survivorship of 'hard' (mature) versus 'soft' (teneral) and 'clawed' (intact)
      versus 'clawless' (surgically removed) weevils. The ecological significance of
      the weevil's hard body was evaluated by assessing the hardness of the weevils,
      the local prey insects, and the bite forces of the lizard populations. The
      existence of toxins or deterrents in the weevil was examined by gas
      chromatography-mass spectrometry (GC-MS). All 'hard' weevils were instantly spat
      out after being bitten once and survived attacks by the lizards. In contrast, the
      'soft' weevils were chewed and subsequently swallowed. The results were the same
      regardless of the presence or absence of the weevil's tarsal claws. The hardness
      of 'hard' Pachyrhynchus weevils was significantly higher than the average
      hardness of other prey insects in the same habitat and the mean bite forces of
      the local lizards. The four candidate compounds of the weevil identified by GC-MS
      had no known toxic or repellent functions against vertebrates. These results
      reveal that the hardness of aposematic prey functions as an effective secondary
      defence, and they provide a framework for understanding the spatio-temporal
      interactions between vertebrate predators and aposematic insect prey.

PMID- 29180598
TI  - Intracellular Distribution of Manganese by the Trans-Golgi Network Transporter
      NRAMP2 Is Critical for Photosynthesis and Cellular Redox Homeostasis.
AB  - Plants require trace levels of manganese (Mn) for survival, as it is an essential
      cofactor in oxygen metabolism, especially O2 production via photosynthesis and
      the disposal of superoxide radicals. These processes occur in specialized
      organelles, requiring membrane-bound intracellular transporters to partition Mn
      between cell compartments. We identified an Arabidopsis thaliana member of the
      NRAMP family of divalent metal transporters, NRAMP2, which functions in the
      intracellular distribution of Mn. Two knockdown alleles of NRAMP2 showed
      decreased activity of photosystem II and increased oxidative stress under Mn
      deficient conditions, yet total Mn content remained unchanged. At the subcellular
      level, these phenotypes were associated with a loss of Mn content in vacuoles and
      chloroplasts. NRAMP2 was able to rescue the mitochondrial yeast mutant mtm1? In
      plants, NRAMP2 is a resident protein of the trans-Golgi network. NRAMP2 may act
      indirectly on downstream organelles by building up a cytosolic pool that is used
      to feed target compartments. Moreover, not only does the nramp2 mutant accumulate
      superoxide ions, but NRAMP2 can functionally replace cytosolic superoxide
      dismutase in yeast, indicating that the pool of Mn displaced by NRAMP2 is
      required for the detoxification of reactive oxygen species.

PMID- 29180600
TI  - Integration of celestial compass cues in the central complex of the locust brain.
AB  - Many insects rely on celestial compass cues such as the polarization pattern of
      the sky for spatial orientation. In the desert locust, the central complex (CX)
      houses multiple sets of neurons, sensitive to the oscillation plane of polarized
      light and thus probably acts as an internal polarization compass. We investigated
      whether other sky compass cues like direct sunlight or the chromatic gradient of
      the sky might contribute to this compass. We recorded from polarization-sensitive
      CX neurons while an unpolarized green or ultraviolet light spot was moved around
      the head of the animal. All types of neuron that were sensitive to the plane of
      polarization (E-vector) above the animal also responded to the unpolarized light
      spots in an azimuth-dependent way. The tuning to the unpolarized light spots was
      independent of wavelength, suggesting that the neurons encode solar azimuth based
      on direct sunlight and not on the sky chromatic gradient. Two cell types
      represented the natural 90 deg relationship between solar azimuth and zenithal E
      vector orientation, providing evidence to suggest that solar azimuth information
      supports the internal polarization compass. Most neurons showed advances in their
      tuning to the E-vector and the unpolarized light spots dependent on rotation
      direction, consistent with anticipatory signaling. The amplitude of responses and
      its variability were dependent on the level of background firing, possibly
      indicating different internal states. The integration of polarization and solar
      azimuth information strongly suggests that besides the polarization pattern of
      the sky, direct sunlight might be an important cue for sky compass navigation in
      the locust.

PMID- 29180601
TI  - Widespread utilization of passive energy recapture in swimming medusae.
AB  - Recently, it has been shown that some medusae are capable of swimming very
      efficiently, i.e. with a low cost of transport, and that this is in part due to
      passive energy recapture (PER) which occurs during bell relaxation. We compared
      the swimming kinematics among a diverse array of medusae, varying in taxonomy,
      morphology and propulsive and foraging modes, in order to evaluate the prevalence
      of PER in medusae. We found that while PER was common among taxa, the magnitude
      of the contribution to overall swimming varied greatly. The ability of medusae to
      utilize PER was not related to morphology and swimming performance but was
      controlled by their swimming kinematics. Utilizing PER required the medusae to
      pause after bell expansion and individuals could modulate their PER by changing
      their pause duration. PER can greatly enhance swimming efficiency but there
      appear to be trade-offs associated with utilizing PER.

PMID- 29180602
TI  - Respiratory mechanics and morphology of Tibetan and Andean high-altitude geese
      with divergent life histories.
AB  - High-altitude bar-headed geese (Anser indicus) and Andean geese (Chloephaga
      melanoptera) have been shown to preferentially increase tidal volume over
      breathing frequency when increasing ventilation during exposure to hypoxia.
      Increasing tidal volume is a more effective breathing strategy but is also
      thought to be more mechanically and metabolically expensive. We asked whether
      there might be differences in the mechanics or morphology of the respiratory
      systems of high-altitude transient bar-headed geese and high-altitude resident
      Andean geese that could minimize the cost of breathing more deeply. We compared
      these two species with a low-altitude migratory species, the barnacle goose
      (Branta leucopsis). We ventilated anesthetized birds to measure mechanical
      properties of the respiratory system and used CT scans to quantify respiratory
      morphology. We found that the respiratory system of Andean geese was
      disproportionately larger than that of the other two species, allowing use of a
      deeper breathing strategy for the same energetic cost. The relative size of the
      respiratory system, especially the caudal air sacs, of bar-headed geese was also
      larger than that of barnacle geese. However, when normalized to respiratory
      system size, the mechanical cost of breathing did not differ significantly among
      these three species, indicating that deeper breathing is enabled by morphological
      but not mechanical differences between species. The metabolic cost of breathing
      was estimated to be <1% of basal metabolic rate at rest in normoxia. Because of
      differences in the magnitude of the ventilatory response, the cost of breathing
      was estimated to increase 7- to 10-fold in bar-headed and barnacle geese in
      severe hypoxia, but less than 1-fold in Andean geese exposed to the same low
      atmospheric PO2.

PMID- 29180603
TI  - Metabolome dynamics of diapause in the butterfly Pieris napi: distinguishing
      maintenance, termination and post-diapause phases.
AB  - Diapause is a deep resting stage facilitating temporal avoidance of unfavourable
      environmental conditions, and is used by many insects to adapt their life cycle
      to seasonal variation. Although considerable work has been invested in trying to
      understand each of the major diapause stages (induction, maintenance and
      termination), we know very little about the transitions between stages,
      especially diapause termination. Understanding diapause termination is crucial
      for modelling and predicting spring emergence and winter physiology of insects,
      including many pest insects. In order to gain these insights, we investigated
      metabolome dynamics across diapause development in pupae of the butterfly Pieris
      napi, which exhibits adaptive latitudinal variation in the length of endogenous
      diapause that is uniquely well characterized. By employing a time-series
      experiment, we show that the whole-body metabolome is highly dynamic throughout
      diapause and differs between pupae kept at a diapause-terminating (low)
      temperature and those kept at a diapause-maintaining (high) temperature. We show
      major physiological transitions through diapause, separate temperature-dependent
      from temperature-independent processes and identify significant patterns of
      metabolite accumulation and degradation. Together, the data show that although
      the general diapause phenotype (suppressed metabolism, increased cold tolerance)
      is established in a temperature-independent fashion, diapause termination is
      temperature dependent and requires a cold signal. This revealed several
      metabolites that are only accumulated under diapause-terminating conditions and
      degraded in a temperature-unrelated fashion during diapause termination. In
      conclusion, our findings indicate that some metabolites, in addition to
      functioning as cryoprotectants, for example, are candidates for having regulatory
      roles as metabolic clocks or time-keepers during diapause.

PMID- 29180605
TI  - Cell-Free DNA and Circulating Tumor Cells: Comprehensive Liquid Biopsy Analysis
      in Advanced Breast Cancer.
AB  - Purpose: Liquid biopsy provides a real-time assessment of metastatic breast
      cancer (MBC). We evaluated the utility of combining circulating tumor cells (CTC)
      and circulating tumor DNA (ctDNA) to predict prognosis in MBC.Experimental
      Design: We conducted a retrospective study of 91 patients with locally advanced
      breast cancer and MBC. CTCs were enumerated by CellSearch; the plasma-based assay
      was performed utilizing Guardant360 and the survival analysis using Kaplan-Meier
      curves.Results: Eighty-four patients had stage IV cancer, and 7 patients had no
      metastases. Eighty patients had CTC analysis: median number 2 (0-5,612). Blood
      samples [232 of 277 (84%)] had mutations. The average ctDNA fraction was 4.5% (0
      88.2%) and number of alterations 3 (0-27); the most commonly mutated genes were
      TP53 (52%), PIK3CA (40%), and ERBB2 (20%). At the time of analysis, 36 patients
      (39.6%) were dead. The median follow-up for CTCs was 9 months; for ctDNA, it was
      9.9 months. For CTCs and ctDNA, respectively, progression-free survival (PFS) was
      4.2 and 5.2 months and overall survival (OS) was 18.7 and 21.5 months. There was
      a statistically significant difference in PFS and OS for baseline CTCs < 5 versus
      CTCs >= 5 (P = 0.021 and P = 0.0004, respectively); %ctDNA < 0.5 versus >= 0.5 (P
      = 0.003 and P = 0.012); number of alterations < 2 versus >= 2 (P = 0.059
      borderline and P = 0.0015). A significant association by Fisher exact test was
      found between the number of alterations and the %ctDNA in the baseline sample (P
      < 0.0001).Conclusions: The study demonstrated that liquid biopsy is an effective
      prognostic tool. Clin Cancer Res; 24(3); 560-8. (c)2017 AACR.

PMID- 29180604
TI  - Classifying Colorectal Cancer by Tumor Location Rather than Sidedness Highlights
      a Continuum in Mutation Profiles and Consensus Molecular Subtypes.
AB  - Purpose: Colorectal cancers are classified as right/left-sided based on whether
      they occur before/after the splenic flexure, with established differences in
      molecular subtypes and outcomes. However, it is unclear if this division is
      optimal and whether precise tumor location provides further
      information.Experimental Design: In 1,876 patients with colorectal cancer, we
      compared mutation prevalence and overall survival (OS) according to side and
      location. Consensus molecular subtype (CMS) was compared in a separate cohort of
      608 patients.Results: Mutation prevalence differed by side and location for TP53,
      KRAS, BRAFV600, PIK3CA, SMAD4, CTNNB1, GNAS, and PTEN Within left- and right
      sided tumors, there remained substantial variations in mutation rates. For
      example, within right-sided tumors, RAS mutations decreased from 70% for cecal,
      to 43% for hepatic flexure location (P = 0.0001), while BRAFV600 mutations
      increased from 10% to 22% between the same locations (P < 0.0001). Within left
      sided tumors, the sigmoid and rectal region had more TP53 mutations (P = 0.027),
      less PIK3CA (P = 0.0009), BRAF (P = 0.0033), or CTNNB1 mutations (P < 0.0001),
      and less MSI (P < 0.0001) than other left-sided locations. Despite this, a
      left/right division preceding the transverse colon maximized prognostic
      differences by side and transverse colon tumors had K-modes mutation clustering
      that appeared more left than right sided. CMS profiles showed a decline in CMS1
      and CMS3 and rise in CMS2 prevalence moving distally.Conclusions: Current
      right/left classifications may not fully recapitulate regional variations in
      tumor biology. Specifically, the sigmoid-rectal region appears unique and the
      transverse colon is distinct from other right-sided locations. Clin Cancer Res;
      24(5); 1062-72. (c)2017 AACRSee related commentary by Dienstmann, p. 989.

PMID- 29180606
TI  - Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates
      Drug-Resistant Human B-cell Malignancies In Vivo.
AB  - Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell
      malignancies, yet many patients develop resistance. Novel therapies against
      alternative targets are needed to circumvent resistance mechanisms. We sought to
      generate mAbs against human B-cell-activating factor receptor (BAFF-R/TNFRSF13C),
      which has not yet been targeted successfully for cancer therapy.Experimental
      Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded
      cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were
      developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The
      chimeric mAbs were tested against human B-cell tumor lines, primary patient
      samples, and drug-resistant tumors.Results: Chimeric antibodies bound with high
      affinity to multiple human malignant B-cell lines and induced potent antibody
      dependent cellular cytotoxicity (ADCC) against multiple subtypes of human
      lymphoma and leukemia, including primary tumors from patients who had relapsed
      after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib
      resistant and rituximab-insensitive CD20-deficient variant lymphomas,
      respectively. Importantly, they demonstrated remarkable in vivo growth inhibition
      of drug-resistant tumor models in immunodeficient mice.Conclusions: Our method
      generated novel anti-BAFF-R antibody therapeutics with remarkable single-agent
      antitumor effects. We propose that these antibodies represent an effective new
      strategy for targeting and treating drug-resistant B-cell malignancies and
      warrant further development. Clin Cancer Res; 24(5); 1114-23. (c)2017 AACR.

PMID- 29180607
TI  - Small-Cell Carcinomas of the Bladder and Lung Are Characterized by a Convergent
      but Distinct Pathogenesis.
AB  - Purpose: Small-cell carcinoma of the bladder (SCCB) is a rare and aggressive
      neuroendocrine tumor with a dismal prognosis and limited treatment options. As
      SCCB is histologically indistinguishable from small-cell lung cancer, a shared
      pathogenesis and cell of origin has been proposed. The aim of this study is to
      determine whether SCCBs arise from a preexisting urothelial carcinoma or share a
      molecular pathogenesis in common with small-cell lung cancer.Experimental Design:
      We performed an integrative analysis of 61 SCCB tumors to identify histology- and
      organ-specific similarities and differences.Results: SCCB has a high somatic
      mutational burden driven predominantly by an APOBEC-mediated mutational process.
      TP53, RB1, and TERT promoter mutations were present in nearly all samples.
      Although these events appeared to arise early in all affected tumors and likely
      reflect an evolutionary branch point that may have driven small-cell lineage
      differentiation, they were unlikely the founding transforming event, as they were
      often preceded by diverse and less common driver mutations, many of which are
      common in bladder urothelial cancers, but not small-cell lung tumors. Most
      patient tumors (72%) also underwent genome doubling (GD). Although arising at
      different chronologic points in the evolution of the disease, GD was often
      preceded by biallelic mutations in TP53 with retention of two intact
      copies.Conclusions: Our findings indicate that small-cell cancers of the bladder
      and lung have a convergent but distinct pathogenesis, with SCCBs arising from a
      cell of origin shared with urothelial bladder cancer. Clin Cancer Res; 24(8);
      1965-73. (c)2017 AACRSee related commentary by Oser and Janne, p. 1775.

PMID- 29180608
TI  - t-Darpp Activates IGF-1R Signaling to Regulate Glucose Metabolism in Trastuzumab
      Resistant Breast Cancer Cells.
AB  - Purpose: Increased glycolysis and glucose dependence is a hallmark of malignancy
      that enables tumors to maximize cell proliferation. In HER2+ cancers, an increase
      in glycolytic capacity is associated with trastuzumab resistance. IGF-1R
      activation and t-Darpp overexpression both confer trastuzumab resistance in
      breast cancer. We therefore investigated a role for IGF-1R and t-Darpp in
      regulating glycolytic capacity in HER2+ breast cancers.Experimental Design: We
      examined the relationship between t-Darpp and IGF-1R expression in breast tumors
      and their respective relationships with patient survival. To assess t-Darpp's
      metabolic effects, we used the Seahorse flux analyzer to measure glucose
      metabolism in trastuzumab-resistant SK-BR-3 cells (SK.HerR) that have high
      endogenous t-Darpp levels and SK.tDrp cells that stably overexpress exogenous t
      Darpp. To investigate t-Darpp's mechanism of action, we evaluated t-Darpp:IGF-1R
      complexes by coimmunoprecipitation and proximity ligation assays. We used pathway
      specific inhibitors to study the dependence of t-Darpp effects on IGF-1R
      signaling. We used siRNA knockdown to determine whether glucose reliance in
      SK.HerR cells was mediated by t-Darpp.Results: In breast tumors, PPP1R1B mRNA
      levels were inversely correlated with IGF-1R mRNA levels and directly associated
      with shorter overall survival. t-Darpp overexpression was sufficient to increase
      glucose metabolism in SK.tDrp cells and essential for the glycolytic phenotype of
      SK.HerR cells. Recombinant t-Darpp stimulated glucose uptake, glycolysis, and IGF
      1R-Akt signaling in SK-BR-3 cells. Finally, t-Darpp stimulated IGF-1R
      heterodimerization with ErbB receptors and required IGF-1R signaling to confer
      its metabolic effects.Conclusions: t-Darpp activates IGF-1R signaling through
      heterodimerization with EGFR and HER2 to stimulate glycolysis and confer
      trastuzumab resistance. Clin Cancer Res; 24(5); 1216-26. (c)2017 AACR.

PMID- 29180610
TI  - Functional Organization and Dynamic Activity in the Superior Colliculus of the
      Echolocating Bat, Eptesicus fuscus.
AB  - Sensory-guided behaviors require the transformation of sensory information into
      task-specific motor commands. Prior research on sensorimotor integration has
      emphasized visuomotor processes in the context of simplified orienting movements
      in controlled laboratory tasks rather than an animal's more complete, natural
      behavioral repertoire. Here, we conducted a series of neural recording
      experiments in the midbrain superior colliculus (SC) of echolocating bats engaged
      in a sonar target-tracking task that invoked dynamic active sensing behaviors. We
      hypothesized that SC activity in freely behaving animals would reveal dynamic
      shifts in neural firing patterns within and across sensory, sensorimotor, and
      premotor layers. We recorded neural activity in the SC of freely echolocating
      bats (three females and one male) and replicated the general trends reported in
      other species with sensory responses in the dorsal divisions and premotor
      activity in ventral divisions of the SC. However, within this coarse functional
      organization, we discovered that sensory and motor neurons are comingled within
      layers throughout the volume of the bat SC. In addition, as the bat increased
      pulse rate adaptively to increase resolution of the target location with closing
      distance, the activity of sensory and vocal premotor neurons changed such that
      auditory response times decreased, and vocal premotor lead times shortened. This
      finding demonstrates that SC activity can be modified dynamically in concert with
      adaptive behaviors and suggests that an integrated functional organization within
      SC laminae supports rapid and local integration of sensory and motor signals for
      natural, adaptive behaviors.SIGNIFICANCE STATEMENT Natural sensory-guided
      behaviors involve the rapid integration of information from the environment to
      direct flexible motor actions. The vast majority of research on sensorimotor
      integration has used artificial stimuli and simplified behaviors, leaving open
      questions about nervous system function in the context of natural tasks. Our work
      investigated mechanisms of dynamic sensorimotor feedback control by analyzing
      patterns of neural activity in the midbrain superior colliculus (SC) of an
      echolocating bat tracking and intercepting moving prey. Recordings revealed that
      sensory and motor neurons comingle within laminae of the SC to support rapid
      sensorimotor integration. Further, we discovered that neural activity in the bat
      SC changes with dynamic adaptations in the animal's echolocation behavior.

PMID- 29180609
TI  - Honokiol Radiosensitizes Squamous Cell Carcinoma of the Head and Neck by
      Downregulation of Survivin.
AB  - Purpose: Previous studies revealed diverging results regarding the role of
      survivin in squamous cell carcinoma of the head and neck (SCCHN). This study
      aimed to evaluate the clinical significance of survivin expression in SCCHN; the
      function of survivin in DNA-damage repair following ionizing radiation therapy
      (RT) in SCCHN cells; and the potential of honokiol to enhance RT through
      downregulation of survivin.Experimental Design: Expression of survivin in SCCHN
      patient primary tumor tissues (n = 100) was analyzed and correlated with clinical
      parameters. SCCHN cell lines were used to evaluate the function of survivin and
      the effects of honokiol on survivin expression in vitro and in vivoResults:
      Overexpression of survivin was significantly associated with lymph nodes'
      metastatic status (P = 0.025), worse overall survival (OS), and disease-free
      survival (DFS) in patients receiving RT (n = 65, OS: P = 0.024, DFS: P = 0.006)
      and in all patients with SCCHN (n = 100, OS: P = 0.002, DFS: P = 0.003). In SCCHN
      cells, depletion of survivin led to increased DNA damage and cell death following
      RT, whereas overexpression of survivin increased clonogenic survival. RT induced
      nuclear accumulation of survivin and its molecular interaction with gamma-H2AX
      and DNA-PKCs. Survivin specifically bound to DNA DSB sites induced by I-SceI
      endonuclease. Honokiol (which downregulates survivin expression) in combination
      with RT significantly augmented cytotoxicity in SCCHN cells with acquired
      radioresistance and inhibited growth in SCCHN xenograft tumors.Conclusions:
      Survivin is a negative prognostic factor and is involved in DNA-damage repair
      induced by RT. Targeting survivin using honokiol in combination with RT may
      provide novel therapeutic opportunities. Clin Cancer Res; 24(4); 858-69. (c)2017
      AACR.

PMID- 29180612
TI  - Clinical Implication of Mycophenolic Acid Trough Concentration Monitoring in
      Kidney Transplant Patients on a Tacrolimus Triple Maintenance Regimen: A Single
      Center Experience.
AB  - BACKGROUND This study was designed to analyze the clinical implications of
      mycophenolic acid trough concentration monitoring. MATERIAL AND METHODS We
      collected data of patients with mycophenolic acid trough concentration monitoring
      after their first kidney transplant between November 2006 and March 2015 who were
      prescribed tacrolimus, mycophenolate, and methylprednisolone. Analyses were
      performed on 3 periods: 1 month, 1 month to 1 year, and after 1 year post
      transplantation. To analyze factors related to acute cellular rejection, logistic
      regression was used for 1 month, while Cox analysis was used during 1 month to 1
      year and after 1 year post-transplantation. RESULTS In the 145 patients receiving
      mycophenolate mofetil, mean tacrolimus trough >=7.0 ng/mL (OR=0.177, CI=0.060
      0.524, p=0.002) and mean mycophenolic acid trough >=1.7 mg/L (OR=0.190, CI=0.040
      0.896, p=0.036) were protective for rejection during 1 month. Mean mycophenolic
      acid trough >=1.7 mg/L (HR=0.179, CI=0.040-0.806, p=0.025) and >=0.7 mg/L
      (HR=0.142, CI=0.028-0.729, p=0.019) were related to better rejection-free
      survival during 1 month to 1 year and after 1 year, respectively. In 399 patients
      receiving enteric-coated mycophenolate sodium, mean tacrolimus trough >=7.0 ng/mL
      (OR=0.258, CI=0.131-0.507, p<0.001) and mean mycophenolic acid trough >=2.1 mg/L
      (OR=0.507, CI=0.264-0.973, p=0.041) were protective for rejection during 1 month.
      Mean mycophenolic acid trough >=1.7 mg/L (HR=0.519, CI=0.289-0.932, p=0.028) and
      >=0.7 mg/L (HR=0.208, CI=0.072-0.602, p=0.004) were related to better rejection
      free survival during 1 month to 1 year and after 1 year, respectively.
      CONCLUSIONS Mycophenolic acid trough concentration monitoring can be useful in
      preventing acute cellular rejection in patients receiving tacrolimus,
      mycophenolate, and methylprednisolone.

PMID- 29180613
TI  - Analysis of Risk Factors for Hypoglycemic Coma in 194 Patients with Type 2
      Diabetes.
AB  - BACKGROUND The present study was conducted to analyze possible risk factors in
      patients with type 2 diabetes who are in hypoglycemic coma. MATERIAL AND METHODS
      A total of 194 patients with type 2 diabetic hypoglycemic coma who were admitted
      to our hospital between January 2010 and January 2016 were included. The patients
      were all in coma on admission, and their blood glucose levels were lower than 2.8
      mmol/L. None of the patients had type I diabetes, specific types of diabetes, or
      gestational diabetes. Multiple linear regression analysis was used to determine
      possible factors associated with hypoglycemic coma. RESULTS Among the patients,
      82 were male and 112 were female (mean age, 66.88+/-10.62 years). In addition, 72
      patients lived in urban areas and 122 lived in rural areas. Occurrence of
      hypoglycemic coma was correlated with difference between urban and rural
      residence, glycosylated hemoglobin (HbA1c) level, combined hypertension, and
      combined neural complications. Self-purchased drugs resulted in significantly
      lower blood glucose level at the onset of hypoglycemic coma than insulin,
      secretagogue, or non-secretagogue drugs. Blood glucose level at onset was
      correlated with season. Patients living in rural areas or with combined
      macrovascular or microvascular complications had prolonged hospital stay and poor
      prognosis. CONCLUSIONS Our results demonstrate that rural residence, higher HbA1c
      level, combined hypertension, and combined neural complications increase the
      incidence of hypoglycemic coma. Use of self-purchased drugs and colder seasons
      may result in lower blood glucose levels in patients with hypoglycemic coma.

PMID- 29180611
TI  - Screening drug effects in patient-derived cancer cells links organoid responses
      to genome alterations.
AB  - Cancer drug screening in patient-derived cells holds great promise for
      personalized oncology and drug discovery but lacks standardization. Whether cells
      are cultured as conventional monolayer or advanced, matrix-dependent organoid
      cultures influences drug effects and thereby drug selection and clinical success.
      To precisely compare drug profiles in differently cultured primary cells, we
      developed DeathPro, an automated microscopy-based assay to resolve drug-induced
      cell death and proliferation inhibition. Using DeathPro, we screened cells from
      ovarian cancer patients in monolayer or organoid culture with clinically relevant
      drugs. Drug-induced growth arrest and efficacy of cytostatic drugs differed
      between the two culture systems. Interestingly, drug effects in organoids were
      more diverse and had lower therapeutic potential. Genomic analysis revealed novel
      links between drug sensitivity and DNA repair deficiency in organoids that were
      undetectable in monolayers. Thus, our results highlight the dependency of
      cytostatic drugs and pharmacogenomic associations on culture systems, and guide
      culture selection for drug tests.

PMID- 29180614
TI  - Isolated C5 Vertebrae Dislocation with Trauma: An Extremely Rare Case of Isolated
      C5 Dislocation.
AB  - BACKGROUND Total spondylolisthesis, or dislocation of 1 cervical vertebrae, is
      only caused by high-energy trauma and is usually fatal. Cervical spine fractures
      and dislocations often cause 3-column structural damage to the cervical spine,
      injury to the spinal cord, and precipitating alignment of the cervical vertebrae,
      as well as cervical instability, which are detrimental, show poor prognosis, and
      are associated with high rates of mortality rate and disability. CASE REPORT We
      report an extremely rare case of isolated C5 dislocation caused by falling out of
      a tree, with sudden tetraplegia. CONCLUSIONS Total spondylolisthesis or
      dislocation of 1 cervical vertebrae can be surgically treated with anterior
      approach because it is possible to completely remove the vertebra body,
      intervertebral disc, and bone fragments, to directly decompress the spinal cord
      with stabilization.

PMID- 29180615
TI  - Evolutionary recruitment of flexible Esrp-dependent splicing programs into
      diverse embryonic morphogenetic processes.
AB  - Epithelial-mesenchymal interactions are crucial for the development of numerous
      animal structures. Thus, unraveling how molecular tools are recruited in
      different lineages to control interplays between these tissues is key to
      understanding morphogenetic evolution. Here, we study Esrp genes, which regulate
      extensive splicing programs and are essential for mammalian organogenesis. We
      find that Esrp homologs have been independently recruited for the development of
      multiple structures across deuterostomes. Although Esrp is involved in a wide
      variety of ontogenetic processes, our results suggest ancient roles in non-neural
      ectoderm and regulating specific mesenchymal-to-epithelial transitions in
      deuterostome ancestors. However, consistent with the extensive rewiring of Esrp
      dependent splicing programs between phyla, most developmental defects observed in
      vertebrate mutants are related to other types of morphogenetic processes. This is
      likely connected to the origin of an event in Fgfr, which was recruited as an
      Esrp target in stem chordates and subsequently co-opted into the development of
      many novel traits in vertebrates.

PMID- 29180616
TI  - Changes in cortical network connectivity with long-term brain-machine interface
      exposure after chronic amputation.
AB  - Studies on neural plasticity associated with brain-machine interface (BMI)
      exposure have primarily documented changes in single neuron activity, and largely
      in intact subjects. Here, we demonstrate significant changes in ensemble-level
      functional connectivity among primary motor cortical (MI) neurons of chronically
      amputated monkeys exposed to control a multiple-degree-of-freedom robot arm. A
      multi-electrode array was implanted in M1 contralateral or ipsilateral to the
      amputation in three animals. Two clusters of stably recorded neurons were
      arbitrarily assigned to control reach and grasp movements, respectively. With
      exposure, network density increased in a nearly monotonic fashion in the
      contralateral monkeys, whereas the ipsilateral monkey pruned the existing network
      before re-forming a denser connectivity. Excitatory connections among neurons
      within a cluster were denser, whereas inhibitory connections were denser among
      neurons across the two clusters. These results indicate that cortical network
      connectivity can be modified with BMI learning, even among neurons that have been
      chronically de-efferented and de-afferented due to amputation.

PMID- 29180618
TI  - A transcribed enhancer dictates mesendoderm specification in pluripotency.
AB  - Enhancers and long noncoding RNAs (lncRNAs) are key determinants of lineage
      specification during development. Here, we evaluate remodeling of the enhancer
      landscape and modulation of the lncRNA transcriptome during mesendoderm
      specification. We sort mesendodermal progenitors from differentiating embryonic
      stem cells (ESCs) according to Eomes expression, and find that enhancer usage is
      coordinated with mesendoderm-specific expression of key lineage-determining
      transcription factors. Many of these enhancers are associated with the expression
      of lncRNAs. Examination of ESC-specific enhancers interacting in three
      dimensional space with mesendoderm-specifying transcription factor loci
      identifies MesEndoderm Transcriptional Enhancer Organizing Region (Meteor).
      Genetic and epigenetic manipulation of the Meteor enhancer reveal its
      indispensable role during mesendoderm specification and subsequent cardiogenic
      differentiation via transcription-independent and -dependent mechanisms.
      Interestingly, Meteor-deleted ESCs are epigenetically redirected towards
      neuroectodermal lineages. Loci, topologically associating a transcribed enhancer
      and its cognate protein coding gene, appear to represent therefore a class of
      genomic elements controlling developmental competence in pluripotency.

PMID- 29180619
TI  - The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO
      conjugation machinery.
AB  - SUMO-targeted ubiquitin ligases (STUbLs) mediate the ubiquitylation of SUMOylated
      proteins to modulate their functions. In search of direct targets for the STUbL
      RNF4, we have developed TULIP (targets for ubiquitin ligases identified by
      proteomics) to covalently trap targets for ubiquitin E3 ligases. TULIP
      methodology could be widely employed to delineate E3 substrate wiring. Here we
      report that the single SUMO E2 Ubc9 and the SUMO E3 ligases PIAS1, PIAS2, PIAS3,
      ZNF451, and NSMCE2 are direct RNF4 targets. We confirm PIAS1 as a key RNF4
      substrate. Furthermore, we establish the ubiquitin E3 ligase BARD1, a tumor
      suppressor and partner of BRCA1, as an indirect RNF4 target, regulated by PIAS1.
      Interestingly, accumulation of BARD1 at local sites of DNA damage increases upon
      knockdown of RNF4. Combined, we provide an insight into the role of the STUbL
      RNF4 to balance the role of SUMO signaling by directly targeting Ubc9 and SUMO E3
      ligases.

PMID- 29180617
TI  - Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor
      suppressor microRNAs.
AB  - The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs
      implicated in human carcinogenesis. Their mechanisms of action and the factors
      regulating their expression in cancers are poorly understood. Here we show that
      high expression of uc.339 correlates with lower survival in 210 non-small cell
      lung cancer (NSCLC) patients. We provide evidence from cell lines and primary
      samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is
      upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p,
      -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these
      microRNAs is upregulated, promoting cancer growth and migration. Finally, we find
      that modulation of uc.339 affects microRNA expression. However, overexpression or
      downregulation of these microRNAs causes no significant variations in uc.339
      levels, suggesting a type of interaction for uc.339 that we call "entrapping".
      Our results support a key role for uc.339 in lung cancer.

PMID- 29180620
TI  - Quantitative measurement of post-concussion syndrome Using
      Electrovestibulography.
AB  - In this study, a noninvasive quantitative measure was used to identify short and
      long term post-concussion syndrome (PCS) both from each other and from healthy
      control populations. We used Electrovestibulography (EVestG) for detecting
      neurophysiological PCS consequent to a mild traumatic brain injury (mTBI) in both
      short-term (N = 8) and long-term (N = 30) (beyond the normal recovery period)
      symptomatic individuals. Peripheral, spontaneously evoked vestibuloacoustic
      signals incorporating - and modulated by - brainstem responses were recorded
      using EVestG, while individuals were stationary (no movement stimulus). Tested
      were 38 individuals with PCS in comparison to those of 33 age-and-gender-matched
      healthy controls. The extracted features were based on the shape of the averaged
      extracted field potentials (FPs) and their detected firing pattern. Linear
      discriminant analysis classification, incorporating a leave-one-out routine,
      resulted in (A) an unbiased 84% classification accuracy for separating healthy
      controls from a mix of long and short-term symptomatology PCS sufferers and (B) a
      79% classification accuracy for separating between long and short-term
      symptomatology PCS sufferers. Comparatively, short-term symptomatology PCS was
      generally detected as more distal from controls. Based on the results, the EVestG
      recording shows promise as an assistive objective tool for detecting and
      monitoring individuals with PCS after normal recovery periods.

PMID- 29180621
TI  - Quantitative analysis of intra- and inter-individual variability of human beta
      cell mass.
AB  - Pancreatic beta-cell mass is a critical determinant of the progression of
      diabetes. The loss of beta-cells in various types of diabetes has been documented
      in comparison to age, sex and body mass index (BMI) matched control subjects.
      However, the underlying heterogeneity of beta-cell mass in healthy individuals
      has not been considered. In this study, the inter-individual heterogeneity in
      beta-cell/islet mass was examined among 10 cases of age-matched non-diabetic male
      subjects in relation to BMI, pancreas weight, and the percent ratio, volume and
      number of islets in the whole pancreas. Beta-cell/islet mass was measured using a
      large-scale unbiased quantification method. In contrast to previous studies, we
      found no clinically relevant correlation between beta-cell/islet mass and age,
      BMI or pancreas weight, with large differences in beta-cell/islet mass and islet
      number among the individuals. Our method extracts the comprehensive information
      out of individual pancreas providing multifaceted parameters to study the
      intrinsic heterogeneity of the human pancreas.

PMID- 29180622
TI  - Calf Circumference as a Novel Tool for Risk of Disability of the Elderly
      Population.
AB  - Disability became increasingly common with age, and crude rates of disability
      were rising around the globe. The aim of this study was to investigate the
      association between calf circumference (CC) and disability in the U.S. elderly
      population. From the 1999-2006 National Health and Nutrition Examination Survey,
      a total of 4,245 participants with an age range of 60-84 years were included.
      Disability was defined as the total number of difficulties within the following 5
      major domains of disability, such as activities of daily living (ADL),
      instrumental ADL, general physical activities, lower extremity mobility, and
      leisure and social activities. The association between CC and disability was
      investigated through the regression model adjusted for multiple covariates.
      According to the fully adjusted model regarding disability, the beta coefficients
      for each quartile of increasing CC were -0.041 for quartile 2 (P = 0.096), -0.060
      for quartile 3 (P = 0.027), and -0.073 for quartile 4 (P = 0.026) respectively,
      compared with lowest quartile. There was a negative association between CC and
      disability among the elderly population. Calf circumference may be a novel risk
      assessment for disability of elderly people.

PMID- 29180623
TI  - Genotyping-by-Sequencing Derived High-Density Linkage Map and its Application to
      QTL Mapping of Flag Leaf Traits in Bread Wheat.
AB  - Winter wheat parents 'Harry' (drought tolerant) and 'Wesley' (drought
      susceptible) were used to develop a recombinant inbred population with future
      goals of identifying genomic regions associated with drought tolerance. To
      precisely map genomic regions, high-density linkage maps are a prerequisite. In
      this study genotyping-by- sequencing (GBS) was used to construct the high-density
      linkage map. The map contained 3,641 markers distributed on 21 chromosomes and
      spanned 1,959 cM with an average distance of 1.8 cM between markers. The
      constructed linkage map revealed strong collinearity in marker order across 21
      chromosomes with POPSEQ-v2.0, which was based on a high-density linkage map. The
      reliability of the linkage map for QTL mapping was demonstrated by co-localizing
      the genes to previously mapped genomic regions for two highly heritable traits,
      chaff color, and leaf cuticular wax. Applicability of linkage map for QTL mapping
      of three quantitative traits, flag leaf length, width, and area, identified 21
      QTLs in four environments, and QTL expression varied across the environments. Two
      major stable QTLs, one each for flag leaf length (Qfll.hww-7A) and flag leaf
      width (Qflw.hww-5A) were identified. The map constructed will facilitate QTL and
      fine mapping of quantitative traits, map-based cloning, comparative mapping, and
      in marker-assisted wheat breeding endeavors.

PMID- 29180624
TI  - Alpha-synuclein facilitates to form short unconventional microtubules that have a
      unique function in the axonal transport.
AB  - Although alpha-synuclein (alphaSyn) has been linked to Parkinson's disease (PD),
      the mechanisms underlying the causative role in PD remain unclear. We previously
      proposed a model for a transportable microtubule (tMT), in which dynein is
      anchored to a short tMT by LIS1 followed by the kinesin-dependent anterograde
      transport; however the mechanisms that produce tMTs have not been determined. Our
      in vitro investigations of microtubule (MT) dynamics revealed that alphaSyn
      facilitates the formation of short MTs and preferentially binds to MTs carrying
      14 protofilaments (pfs). Live-cell imaging showed that alphaSyn co-transported
      with dynein and mobile betaIII-tubulin fragments in the anterograde transport.
      Furthermore, bi-directional axonal transports are severely affected in alphaSyn
      and gammaSyn depleted dorsal root ganglion neurons. SR-PALM analyses further
      revealed the fibrous co-localization of alphaSyn, dynein and betaIII-tubulin in
      axons. More importantly, 14-pfs MTs have been found in rat femoral nerve tissue,
      and they increased approximately 19 fold the control in quantify upon nerve
      ligation, indicating the unconventional MTs are mobile. Our findings indicate
      that alphaSyn facilitates to form short, mobile tMTs that play an important role
      in the axonal transport. This unexpected and intriguing discovery related to
      axonal transport provides new insight on the pathogenesis of PD.

PMID- 29180625
TI  - Differential prognostic value of MYC immunohistochemistry in subtypes of
      papillary renal cell carcinoma.
AB  - The histomorphological subtyping of papillary renal cell carcinomas (pRCCs) has
      improved the predictions of patients' long-term survival. Based on our previous
      results, we hypothesized that the MYC proto-oncogene would show differential
      expression in pRCC subtypes. Using a multi-institutional cohort of 204 pRCC
      patients we assessed the additional value of the immunohistochemical markers MYC,
      MINA53, and Ki67 in predicting patient's long-term survival. The clinical
      endpoints were overall survival (OS) and cancer-specific survival (CSS).
      Nomograms were constructed to predict each patient's risk of death (OS). The
      incorporation of the MYC staining patterns allowed the stratification of pRCC
      type 1 patients into better and worse prognostic groups. None of the patients
      with pRCC type 1 tumors and favorable MYC staining patterns died from tumor
      related causes. This prognostic value was independent of the patient's age at
      surgery, the pathological tumor stage and presence of lymph node invasion. we
      could show that the immunohistochemical assessment of MYC and the
      histomorphological subtyping of pRCC stratifies pRCC type 1 tumors with regard to
      OS and CSS. The determination of the histomorphologic pRCC subtype in combination
      with the MYC immunohistochemical staining patterns allows a more accurate
      prediction of patients' individual risk of death.

PMID- 29180627
TI  - Characteristics of martensitic and strain-glass transitions of the Fe-substituted
      TiNi shape memory alloys probed by transport and thermal measurements.
AB  - The electrical resistivity, Seebeck coefficient, thermal conductivity, and
      specific heat of Ti50Ni50-x Fe x (x = 2.0-10.0 at.%) shape memory alloys (SMAs)
      were measured to investigate the influence of point defects (Fe) on the
      martensitic transformation characteristics. Our results show that the Ti50Ni48Fe2
      and Ti50Ni47Fe3 SMAs have a two-step martensitic transformation (B2 -> R and R ->
      B19'), while the Ti50Ni46Fe4, Ti50Ni44.5Fe5.5, and Ti50Ni44Fe6 SMAs display a one
      step martensitic transition (B2 -> R). However, the compounds Ti50Ni42Fe8 and
      Ti50Ni40Fe10 show strain glass features (frozen strain-ordered state).
      Importantly, the induced point defects significantly alter the martensitic
      transformation characteristics, namely transition temperature and width of
      thermal hysteresis during the transition. This can be explained by the
      stabilization of austenite B2 phase upon Fe substitution, which ultimately leads
      to the decrease in enthalpy that associated to the martensitic transition. To
      determine the boundary composition that separates the R-phase and strain glass
      systems in this series of SMAs, a Ni-rich specimen Ti49Ni45Fe6 was fabricated.
      Remarkably, a slight change in Ti/Ni ratio converts Ti49Ni45Fe6 SMA into a strain
      glass system. Overall, the evolution of phase transformation in the Fe
      substituted TiNi SMAs is presumably caused by the changes in local lattice
      structure via the induced local strain fields by Fe point defects.

PMID- 29180626
TI  - Mitochondrial dynamics controls anti-tumour innate immunity by regulating CHIP
      IRF1 axis stability.
AB  - Macrophages, dendritic cells and other innate immune cells are involved in
      inflammation and host defense against infection. Metabolic shifts in
      mitochondrial dynamics may be involved in Toll-like receptor agonist-mediated
      inflammatory responses and immune cell polarization. However, whether the
      mitochondrial morphology in myeloid immune cells affects anti-tumor immunity is
      unclear. Here we show that FAM73b, a mitochondrial outer membrane protein, has a
      pivotal function in Toll-like receptor-regulated mitochondrial morphology
      switching from fusion to fission. Switching to mitochondrial fission via ablation
      of Fam73b (also known as Miga2) promotes IL-12 production. In tumor-associated
      macrophages, this switch results in T-cell activation and enhances anti-tumor
      immunity. We also show that the mitochondrial morphology affects Parkin
      expression and its recruitment to mitochondria. Parkin controls the stability of
      the downstream CHIP-IRF1 axis through proteolysis. Our findings identify
      mechanisms associated with mitochondrial dynamics that control anti-tumor immune
      responses and that are potential targets for cancer immunotherapy.

PMID- 29180629
TI  - Transcriptome profile analysis reveals the regulation mechanism of floral sex
      differentiation in Jatropha curcas L.
AB  - The seeds of Jatropha curcas contain a high percentage of biodiesel. However, low
      seed yield which was limited by its poor female flowers was a bottleneck for its
      utilization. Here, we compared the transcriptomic profiles of five different
      samples during floral sex differentiation stages using Illumina Hiseq 4000. Our
      results showed that hundreds of differentially expressed genes (DEGs) were
      detected in floral sex initiation period, but thousands of DEGs were involved in
      the stamens and ovules development process. Moreover, the DEGs were mainly shown
      up-regulation in male floral initiation, but mainly down-regulation in female
      floral initiation. Male floral initiation was associated with the flavonoid
      biosynthesis pathway while female floral initiation was related to the
      phytohormone signal transduction pathway. Cytokinin (CTK) signaling triggered the
      initiation of female floral primordium, thereafter other phytohormones co
      promoted the female floral development. In addition, the floral organ identity
      genes played important roles in floral sex differentiation process and displayed
      a general conservation of the ABCDE model in J. curcas. To the best of our
      knowledge, this data is the first comprehensive analysis of the underlying
      regulatory mechanism and the related genes during floral sex differentiation in
      J. curcas, which help in engineering high-yielding varieties of J. curcas.

PMID- 29180628
TI  - Parkin targets HIF-1alpha for ubiquitination and degradation to inhibit breast
      tumor progression.
AB  - Mutations in E3 ubiquitin ligase Parkin have been linked to familial Parkinson's
      disease. Accumulating evidence suggests that Parkin is a tumor suppressor, but
      the underlying mechanism is poorly understood. Here we show that Parkin is an E3
      ubiquitin ligase for hypoxia-inducible factor 1alpha (HIF-1alpha). Parkin
      interacts with HIF-1alpha and promotes HIF-1alpha degradation through
      ubiquitination, which in turn inhibits metastasis of breast cancer cells. Parkin
      downregulation in breast cancer cells promotes metastasis, which can be inhibited
      by targeting HIF-1alpha with RNA interference or the small-molecule inhibitor YC
      1. We further identify lysine 477 (K477) of HIF-1alpha as a major ubiquitination
      site for Parkin. K477R HIF-1alpha mutation and specific cancer-associated Parkin
      mutations largely abolish the functions of Parkin to ubiquitinate HIF-1alpha and
      inhibit cancer metastasis. Importantly, Parkin expression is inversely correlated
      with HIF-1alpha expression and metastasis in breast cancer. Our results reveal an
      important mechanism for Parkin in tumor suppression and HIF-1alpha regulation.

PMID- 29180630
TI  - ATF4 overexpression induces early onset of hyperlipidaemia and hepatic steatosis
      and enhances adipogenesis in zebrafish.
AB  - Activating transcription factor 4 (ATF4) is constitutively expressed in a variety
      of tissues, and regulates several pathological features associated with metabolic
      diseases such as non-alcoholic fatty liver diseases (NAFLD) and obesity. However,
      the role of ATF4 in animal model systems is poorly understood. To investigate
      ATF4 functions in zebrafish, we conditionally expressed ATF4 proteins, using a
      Tet-off transgenic system. We observed early-onset hyperlipidaemia and liver
      steatosis in ATF4 transgenic zebrafish (ATs) without doxycycline treatment (ATs -
      Dox). Oil Red O (ORO)-stained signals were predominant in the intravascular blood
      vessels and liver buds of larval ATs - Dox, indicating that ATF4 functionally
      promotes lipogenesis. Further, ATF4 overexpression accompanied the stimulation of
      the unfolded protein response. Therefore, adult ATs - Dox showed increased lipid
      accumulation, which led, in turn, to liver steatosis. Liver histology and ORO
      staining of ATs - Dox hepatocytes also indicated oxidative stress and induced
      NASH-like phenotypes. Moreover, ATF4 overexpression accelerated adipocyte
      differentiation via CCAAT enhancer binding protein-beta and peroxisome
      proliferator activated receptor-gamma inducible expression. ATs-Dox zebrafish
      showed increased weight gain with larger fat pads due to adipocyte hyperplasia.
      In this study, we report that ATF4 is a potential stimulator of lipid
      biosynthesis and adipogenesis in zebrafish.

PMID- 29180631
TI  - STRT-seq-2i: dual-index 5' single cell and nucleus RNA-seq on an addressable
      microwell array.
AB  - Single-cell RNA-seq has become routine for discovering cell types and revealing
      cellular diversity, but archived human brain samples still pose a challenge to
      current high-throughput platforms. We present STRT-seq-2i, an addressable 9600
      microwell array platform, combining sampling by limiting dilution or FACS, with
      imaging and high throughput at competitive cost. We applied the platform to fresh
      single mouse cortical cells and to frozen post-mortem human cortical nuclei,
      matching the performance of a previous lower-throughput platform while retaining
      a high degree of flexibility, potentially also for other high-throughput
      applications.

PMID- 29180632
TI  - Microfluidic-assisted Formation of Highly Monodisperse and Mesoporous Silica Soft
      Microcapsules.
AB  - The fabrication of mesoporous silica microcapsules with a highly controlled
      particle size ranging in the micrometer size presents a major challenge in many
      academic and industrial research areas, such as for the developement of smart
      drug delivery systems with a well controlled loading and release of (bio)active
      molecules. Many studies based on the solvent evaporation or solvent diffusion
      methods have been developed during the last two decades in order to control the
      particle size, which is often found to range at a sub-micrometer scale. Droplet
      based microfluidics proved during the last decade a powerful tool to produce
      highly monodisperse and mesoporous silica solid microspheres with a controllable
      size in the micrometer range. We show in the present study, in contrast with
      previous microfluidic-assisted approaches, that a better control of the diffusion
      of the silica precursor sol in a surrounding perfluorinated oil phase during the
      silica formation process allows for the formation of highly monodisperse
      mesoporous silica microcapsules with a diameter ranging in the 10 micrometer
      range. We show also, using optical, scanning and transmission electron
      microscopies, small angle x-ray diffraction and BET measurements, that the
      synthesized mesoporous silica microcapsules exhibit a soft-like thin shell with a
      thickness of about 1 MUm, across which 5.9 nm sized mesopores form a well-ordered
      hexagonal 2D network. We suggest and validate experimentally a model where the
      formation of such microcapsules is controlled by the solvent evaporation process
      at the droplet-air interface.

PMID- 29180633
TI  - Integrating evolutionary dynamics into treatment of metastatic castrate-resistant
      prostate cancer.
AB  - Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting
      CYP17A, an enzyme for testosterone auto-production. With standard dosing,
      evolution of resistance with treatment failure (radiographic progression) occurs
      at a median of ~16.5 months. We hypothesize time to progression (TTP) could be
      increased by integrating evolutionary dynamics into therapy. We developed an
      evolutionary game theory model using Lotka-Volterra equations with three
      competing cancer "species": androgen dependent, androgen producing, and androgen
      independent. Simulations with standard abiraterone dosing demonstrate strong
      selection for androgen-independent cells and rapid treatment failure. Adaptive
      therapy, using patient-specific tumor dynamics to inform on/off treatment cycles,
      suppresses proliferation of androgen-independent cells and lowers cumulative drug
      dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations
      of tumor burdens; median TTP is at least 27 months with reduced cumulative drug
      use of 47% of standard dosing. The outcomes show significant improvement over
      published studies and a contemporaneous population.

PMID- 29180634
TI  - Transient locking of the hook procures enhanced motility to flagellated bacteria.
AB  - Flagellated bacteria often proliferate in inhomogeneous environments, such as
      biofilms, swarms and soil. In such media, bacteria are observed to move
      efficiently only if they can get out of "dead ends" by changing drastically their
      swimming direction, and even to completely reverse it. Even though these
      reorientations are ubiquitous, we have only recently begun to describe and
      understand how they happen. In the present work, we visualized the flagella of
      bacteria swimming in a soft agar solution. The surprising observation that the
      filaments do not rotate while being flipped from one side of the cell to the
      other suggests that reversals are driven directly by the motor rather than by the
      thrust created by the rotating filament. This was confirmed by observing bacteria
      in a liquid crystal, where the linear movement of bacteria greatly simplifies the
      analysis. These observations suggest that the reversal and reorientation
      processes involve a temporary locking of the flagellum's hook, which is the
      normally flexible joint between the rotary motor and the long helical filament
      that propels the cell. This newly described locked-hook mode occurs only when the
      motor switches to a clockwise rotation. That correlates with other phenomena that
      are triggered by a switch in one direction and not the other.

PMID- 29180635
TI  - Food availability drives plastic self-repair response in a basal metazoan- case
      study on the ctenophore Mnemiopsis leidyi A. Agassiz 1865.
AB  - Many marine invertebrates including ctenophores are capable of extensive body
      regeneration when injured. However, as for the invasive ctenophore Mnemiopsis
      leidyi, there is a constant subportion of individuals not undergoing whole body
      regeneration but forming functionally stable half-animals instead. Yet, the
      driving factors of this phenomenon have not been addressed so far. This study
      sheds new light on how differences in food availability affect self-repair choice
      and regeneration success in cydippid larvae of M. leidyi. As expected, high food
      availability favored whole-body regeneration. However, under low food conditions
      half-animals became the preferential self-repair mode. Remarkably, both
      regenerating and half-animals showed very similar survival chances under
      respective food quantities. As a consequence of impaired food uptake after
      injury, degeneration of the digestive system would often occur indicating limited
      energy storage capacities. Taken together, this indicates that half-animals may
      represent an alternative energy-saving trajectory which implies self-repair
      plasticity as an adaptive trade-off between high regeneration costs and low
      energy storage capacities. We conclude that self-repair plasticity could lead to
      higher population fitness of ctenophores under adverse conditions such as in
      ships' ballast water tanks which is postulated to be the major vector source for
      the species' spreading around the globe.

PMID- 29180636
TI  - Anterior cervical discectomy and fusion surgery versus total disc replacement: A
      comparative study with minimum of 10-year follow-up.
AB  - Based on long-term follow-ups, this study was designed to investigate the
      incidence and risk factors for postoperative adjacent segment degeneration (ASD)
      after anterior cervical discectomy and fusion (ACDF) or total disc replacement
      (TDR) in treating cervical degenerative diseases. Between January 2000 and
      December 2005, 108 cases undergoing ACDF and 78 undergoing TDR, were enrolled
      into this study. All medical records were retrospectively collected. Every
      patient was followed up at least 10 years. Outcome assessment included visual
      analogue scale (VAS) score, Neck Disability Index (NDI) score, Japanese
      Orthopaedic Association (JOA) score, and radiographic parameters. Consequently,
      thirty-eight (35.2%) of 108 cases suffered from ASD in ACDF group, and 26 (33.3%)
      of 78 cases in TDR group. There was no statistical difference between the two
      groups regarding ASD incidence, VAS/NDI/JOA score, recovery rate. Logistic
      regression analysis showed that age (OR = 2.86, 95% CI, 1.58-4.14) and
      preoperative segmental lordosis (OR = 1.90, 95% CI, 1.05-3.20) were risk factors
      associated with increased odds of ASD regardless of surgical procedures. On the
      other hand, preoperative overall lordosis (OR = 0.54, 95% CI, 0.26-0.82) was most
      likely protective. In conclusion, advanced age and preoperative segmental
      lordosis were identified as risk factors for postoperative ASD, while
      preoperative overall lordosis proves to be a protective factor.

PMID- 29180637
TI  - Present and past selves: a steady-state visual evoked potentials approach to self
      face processing.
AB  - The self-face has a prioritized status in the processing of incoming visual
      inputs. As the self-face changes over the lifespan, this stimulus seems to be
      well-suited for investigation of the self across time. Here, steady-state visual
      evoked potentials (SSVEP, oscillatory responses to periodic stimulation with a
      frequency that mirrors the frequency of stimulation) were used to investigate
      this topic. Different types of faces (present self, past self, close-other's,
      unknown, scrambled) flickered four times per second in two types of stimulation
      ('identical', with the same image of a given type of face; 'different', with
      different images of the same type of face). Each of the 10 stimulation sessions
      lasted 90 seconds and was repeated three times. EEG data were recorded and
      analyzed in 20 participants. In general, faces evoked higher SSVEP than scrambled
      faces. The impact of identical and different stimulation was similar for faces
      and scrambled faces: SSVEP to different stimuli (faces, scrambled faces) was
      enhanced in comparison to identical ones. Present self-faces evoked higher SSVEP
      responses than past self-faces in the different stimulation condition only. Thus,
      our results showed that the physical aspects of the present and past selves are
      differentiated on the neural level in the absence of an overt behavior.

PMID- 29180638
TI  - Clipping has stronger effects on plant production than does warming in three
      alpine meadow sites on the Northern Tibetan Plateau.
AB  - The relative effects of warming and clipping on vegetation growth are not fully
      understood. Therefore, we compared the relative effects of experimental warming
      and clipping on the normalised difference vegetation index (NDVI), green NDVI
      (GNDVI), soil-adjusted vegetation index (SAVI), aboveground biomass (AGB) and
      gross primary production (GPP) in three alpine meadow sites (A, B and C) on the
      Northern Tibetan Plateau from 2013 to 2015. There were no obvious effects of
      experimental warming on the NDVI, GNDVI, SAVI, AGB and GPP at the three sites,
      which were most likely attributed to experimental warming-induced warming and
      drying conditions. In contrast, clipping significantly decreased the NDVI, SAVI
      and AGB by 27.8%, 31.3% and 18.2% at site A, by 27.1%, 31.8% and 27.7% at site B,
      and by 12.3%, 15.1% and 17.6% at site C, respectively. Clipping also
      significantly reduced the GNDVI and GPP by 11.1% and 28.2% at site A and by 18.9%
      and 33.7% at site B, respectively. Clipping marginally decreased the GNDVI by
      8.7% (p = 0.060) and GPP (p = 0.082) by 14.4% at site C. Therefore, clipping had
      stronger effects on vegetation growth than did warming in the three alpine meadow
      sites on the Tibetan Plateau.

PMID- 29180639
TI  - The chromatin remodeling factor ISW-1 integrates organismal responses against
      nuclear and mitochondrial stress.
AB  - Age-associated changes in chromatin structure have a major impact on organismal
      longevity. Despite being a central part of the ageing process, the organismal
      responses to the changes in chromatin organization remain unclear. Here we show
      that moderate disturbance of histone balance during C. elegans development alters
      histone levels and triggers a stress response associated with increased
      expression of cytosolic small heat-shock proteins. This stress response is
      dependent on the transcription factor, HSF-1, and the chromatin remodeling
      factor, ISW-1. In addition, we show that mitochondrial stress during
      developmental stages also modulates histone levels, thereby activating a
      cytosolic stress response similar to that caused by changes in histone balance.
      These data indicate that histone and mitochondrial perturbations are both
      monitored through chromatin remodeling and involve the activation of a cytosolic
      response that affects organismal longevity. HSF-1 and ISW-1 hence emerge as a
      central mediator of this multi-compartment proteostatic response regulating
      longevity.

PMID- 29180640
TI  - Young onset type 2 diabetic patients might be more sensitive to metformin
      compared to late onset type 2 diabetic patients.
AB  - It is unknown whether YOD (young onset diabetes) and LOD (late onset diabetes)
      require similar insulin doses for intensive insulin therapy with a metformin add
      on to achieve glycemic control. We analyzed data from our two previously
      performed randomized, controlled open-label trials. Patients were randomized to
      receive either continuous subcutaneous insulin infusion (CSII) therapy or CSII
      combined with metformin therapy for 4 weeks. The studies concentrated on the
      differences in the insulin doses used for the two groups. We included 36 YOD (age
      < 40 yrs) and 152 LOD (age > 40 yrs) patients. YOD patients who received
      metformin combined with CSII therapy required significantly lower insulin doses
      to maintain euglycemic control compared to patients with LOD. A multivariate
      analysis, controlled for gender and the fasting blood concentration, was
      performed to determine the significance of the differences between groups,
      particularly with respect to the total and basal insulin doses. There was a trend
      toward improvement in beta-cell function and insulin resistance in terms of
      DeltaHOMA-B and DeltaHOMA-IR in patients with YOD compared to those with LOD.
      Newly diagnosed T2D patients with YOD required significantly lower insulin doses,
      particularly basal insulin doses, to maintain glycemic control compared to the
      LOD patients.

PMID- 29180641
TI  - A sensitive and rapid immunoassay for Mycoplasma pneumoniae in children with
      pneumonia based on single-walled carbon nanotubes.
AB  - Mycoplasma pneumoniae(MP) is a leading pathogen of respiratory infection,
      especially community-acquired pneumonia (CAP), in children worldwide. However,
      its diagnosis is frequently ineffective because bacterial culture and serology
      test are usually positive 1-2 weeks or more after the disease onset. To achieve a
      better detection efficiency, the single-walled carbon nanotubes(SWCNT) were
      coupled with the colloidal gold-monoclonal antibody immunochromatographic
      strips(CGIC). Interestingly, the SWCNT/CGIC assay allowed MP identification, with
      a detection limit of 1 * 102 copies/ml. Using referenced throat swabs of 97 MP
      and 40 non-MP cases, the assay yielded 72.2% sensitivity, 100.0% specificity,
      100.0% positive predictive value (PPV), 59.7% negative predictive value (NPV). In
      summary, our assay was far more effective than any conventional methods for the
      diagnosis of acute MP. The ease of use, rapid and stability further enhance its
      feasibility for clinical use on-site.

PMID- 29180642
TI  - A new structural arrangement in proteins involving lysine NH3+ group and
      carbonyl.
AB  - Screening of the Protein Data Bank led to identification of a recurring
      structural motif where lysine NH3+ group interacts with backbone carbonyl. This
      interaction is characterized by linear atom arrangement, with carbonyl O atom
      positioned on the three-fold symmetry axis of the NH3+ group (angle Cepsilon
      Nzeta-O close to 180 degrees , distance Nzeta-O ca. 2.7-3.0 A). Typically, this
      linear arrangement coexists with three regular hydrogen bonds formed by lysine
      NH3+ group (angle Cepsilon-Nzeta-acceptor atom close to 109 degrees , distance
      Nzeta-acceptor atom ca. 2.7-3.0 A). Our DFT calculations using polarizable
      continuum environment suggest that this newly identified linear interaction makes
      an appreciable contribution to protein's energy balance, up to 2 kcal/mol. In the
      context of protein structure, linear interactions play a role in capping the C
      termini of alpha-helices and 310-helices. Of note, linear interaction involving
      conserved lysine is consistently found in the P-loop of numerous NTPase domains,
      where it stabilizes the substrate-binding conformation of the P-loop. Linear
      interaction NH3+ - carbonyl represents an interesting example of ion-dipole
      interactions that has so far received little attention compared to ion-ion
      interactions (salt bridges) and dipole-dipole interactions (hydrogen bonds), but
      nevertheless represents a distinctive element of protein architecture.

PMID- 29180643
TI  - Impact of Oxidant Gases on the Relationship between Outdoor Fine Particulate Air
      Pollution and Nonaccidental, Cardiovascular, and Respiratory Mortality.
AB  - Outdoor fine particulate air pollution (PM2.5) is known to increase mortality
      risk and is recognized as an important contributor to global disease burden.
      However, less is known about how oxidant gases may modify the chronic health
      effects of PM2.5. In this study, we examined how the oxidant capacity of O3 and
      NO2 (using a redox-weighted average, Ox) may modify the relationship between
      PM2.5 and mortality in the 2001 Canadian Census Health and Environment Cohort. In
      total, 2,448,500 people were followed over a 10.6-year period. Each 3.86 ug/m3
      increase in PM2.5 was associated with nonaccidental (Hazard Ratio (HR) = 1.095,
      95% CI: 1.077, 1.112), cardiovascular (HR = 1.088, 95% CI: 1.059, 1.118), and
      respiratory mortality (HR = 1.110, 95% CI: 1.051, 1.171) in the highest tertile
      of Ox whereas weaker/null associations were observed in the middle and lower
      tertiles. Analysis of joint non-linear concentration-response relationships for
      PM2.5 and Ox suggested threshold concentrations between approximately 23 and 25
      ppb with Ox concentrations above these values strengthening PM2.5-mortality
      associations. Overall, our findings suggest that oxidant gases enhance the
      chronic health risks of PM2.5. In some areas, reductions in Ox concentrations may
      have the added benefit of reducing the public health impacts of PM2.5 even if
      mass concentrations remain unchanged.

PMID- 29180644
TI  - Genome editing for the reproduction and remedy of human diseases in mice.
AB  - With the recent progress in genome-editing technologies, such as the CRISPR/Cas9
      system, genetically modified animals carrying nucleotide substitutions or large
      chromosomal rearrangements can be produced rapidly and at low cost. Such genome
      editing techniques have been applied in the generation of animal models,
      especially mice, for reproducing human disease mutations, such as single
      nucleotide polymorphisms (SNPs) or large chromosomal rearrangements identified by
      genome-wide screening analyses. While application methods are under development
      for various complex mutations involving genome editing for mimicking human
      disease-causing mutations in mice, functional studies of mouse models carrying
      replicated human mutations are gradually being published. In this review, we
      discuss the recent progress in application methods of the CRISPR/Cas9 system,
      focusing on the production of mouse models of diseases.

PMID- 29180646
TI  - Phytoplankton communities determine the spatio-temporal heterogeneity of alkaline
      phosphatase activity: evidence from a tributary of the Three Gorges Reservoir.
AB  - In order to reveal the role of phytoplankton in the spatio-temporal distribution
      of alkaline phosphatase activity (APA), monthly investigations were conducted in
      the Xiaojiang River, a tributary of the Three Gorges Reservoir in China.
      Different APA fractions, environmental parameters, and phytoplankton communities
      were followed. High spatio-temporal variations of APA were observed, with the
      highest value in summer and the lowest in winter. The annual average APAT (total
      alkaline phosphatase activity) ranged from 7.78-14.03 nmol?L-1?min-1 with the
      highest in the midstream and the lowest in the estuary. The dominant
      phytoplankton phyla in summer and winter were Cyanophyta and Bacillariophyta,
      respectively. The mean cell density in the midstream and in the estuary was 5.2 *
      107 cell?L-1 and 1.4 * 107 cell?L-1, respectively. That APA>3.0 MUm was
      significantly higher than APA0.45-3 MUm indicating phytoplankton was the main
      contributor to alkaline phosphatase. Correlation analysis indicated the dominant
      species and cell density could determine the distribution pattern of APA.
      Turbidity, total phosphorus, chemical oxygen demand, water temperature (WT), pH
      and chlorophyll a were proved to be positively correlated with APA; soluble
      reactive phosphorus, conductivity, transparency and water level(WL) were
      negatively correlated with APA. It was concluded that spatio-temporal
      heterogeneity of APA determined by phytoplankton communities was related to WT
      and WL.

PMID- 29180645
TI  - Combinations of chromosome transfer and genome editing for the development of
      cell/animal models of human disease and humanized animal models.
AB  - Chromosome transfer technology, including chromosome modification, enables the
      introduction of Mb-sized or multiple genes to desired cells or animals. This
      technology has allowed innovative developments to be made for models of human
      disease and humanized animals, including Down syndrome model mice and humanized
      transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are
      developing rapidly, and permit modifications such as gene knockout and knockin to
      be performed in various cell lines and animals. This review summarizes chromosome
      transfer-related technologies and the combined technologies of chromosome
      transfer and genome editing mainly for the production of cell/animal models of
      human disease and humanized animal models. Specifically, these include: (1)
      chromosome modification with genome editing in Chinese hamster ovary cells and
      mouse A9 cells for efficient transfer to desired cell types; (2) single
      nucleotide polymorphism modification in humanized Tc mice with genome editing;
      and (3) generation of a disease model of Down syndrome-associated hematopoiesis
      abnormalities by the transfer of human chromosome 21 to normal human embryonic
      stem cells and the induction of mutation(s) in the endogenous gene(s) with genome
      editing. These combinations of chromosome transfer and genome editing open up new
      avenues for drug development and therapy as well as for basic research.

PMID- 29180647
TI  - Prediction of postoperative outcomes using intraoperative hemodynamic monitoring
      data.
AB  - Major surgeries can result in high rates of adverse postoperative events.
      Reliable prediction of which patient might be at risk for such events may help
      guide peri- and postoperative care. We show how archiving and mining of
      intraoperative hemodynamic data in orthotopic liver transplantation (OLT) can aid
      in the prediction of postoperative 180-day mortality and acute renal failure
      (ARF), improving upon predictions that rely on preoperative information only.
      From 101 patient records, we extracted 15 preoperative features from clinical
      records and 41 features from intraoperative hemodynamic signals. We used logistic
      regression with leave-one-out cross-validation to predict outcomes, and
      incorporated methods to limit potential model instabilities from feature
      multicollinearity. Using only preoperative features, mortality prediction
      achieved an area under the receiver operating characteristic curve (AUC) of 0.53
      (95% CI: 0.44-0.78). By using intraoperative features, performance improved
      significantly to 0.82 (95% CI: 0.56-0.91, P = 0.001). Similarly, including
      intraoperative features (AUC = 0.82; 95% CI: 0.66-0.94) in ARF prediction
      improved performance over preoperative features (AUC = 0.72; 95% CI: 0.50-0.85),
      though not significantly (P = 0.32). We conclude that inclusion of intraoperative
      hemodynamic features significantly improves prediction of postoperative events in
      OLT. Features strongly associated with occurrence of both outcomes included
      greater intraoperative central venous pressure and greater transfusion volumes.

PMID- 29180648
TI  - CSA13 inhibits colitis-associated intestinal fibrosis via a formyl peptide
      receptor like-1 mediated HMG-CoA reductase pathway.
AB  - Many Crohn's disease (CD) patients develop intestinal strictures, which are
      difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares
      cationic nature and antimicrobial function with antimicrobial peptide
      cathelicidin. As many functions of cathelicidin are mediated through formyl
      peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti
      fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical
      data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated
      intestinal fibrosis mouse model with the administration of CSA13 was used.
      Colonic FPRL1 mRNA expression was positively correlated with the histology scores
      of inflammatory bowel disease patients. In CD patients, colonic FPRL1 mRNA was
      positively correlated with intestinal stricture. CSA13 administration ameliorated
      intestinal fibrosis without influencing intestinal microbiota. Inhibition of
      FPRL1, but not suppression of intestinal microbiota, reversed these protective
      effects of CSA13. Metabolomic analysis indicated increased fecal mevalonate
      levels in the TNBS-treated mice, which were reduced by the CSA13 administration.
      CSA13 inhibited colonic HMG-CoA reductase activity in an FPRL1-dependent manner.
      Mevalonate reversed the anti-fibrogenic effect of CSA13. The increased colonic
      FPRL1 expression is associated with severe mucosal disease activity and
      intestinal stricture. CSA13 inhibits intestinal fibrosis via FPRL1-dependent
      modulation of HMG-CoA reductase pathway.

PMID- 29180650
TI  - A Route to Terahertz Metamaterial Biosensor Integrated with Microfluidics for
      Liver Cancer Biomarker Testing in Early Stage.
AB  - Engineered Terahertz (THz) metamaterials presented an unique characteristics for
      biosensing application due to their accurately tunable resonance frequency, which
      is in accord with vibrational frequency of some important biomolecules such as
      cancer biomarker. However, water absorption in THz regime is an obstacle to
      extend application in trace biomolecules of cancer antibody or antigen. Here, to
      overcome water absorption and enhance the THz biosensing sensitivity, two kinds
      of THz metamaterials biosensor integrated with microfluidics were fabricated and
      used to detect the Alpha fetoprotein (AFP) and Glutamine transferase isozymes II
      (GGT-II) of liver cancer biomarker in early stage. There were about 19 GHz
      resonance shift (5 mu/ml) and 14.2 GHz resonance shift (0.02524 MUg/ml) for GGT
      II and AFP with a two-gap-metamaterial, respectively, which agreed with
      simulation results. Those results demonstrated the power and usefulness of
      metamaterial-assisted THz spectroscopy in trace cancer biomarker molecular
      detection for biological and chemical sensing. Moreover, for a particular cancer
      biomarker, the sensitivity could be further improved by optimizing the
      metamaterial structure and decreasing the permittivity of the substrate. This
      method might be powerful and potential for special recognition of cancer
      molecules in the early stage.

PMID- 29180649
TI  - Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced
      inflammation to insulin resistance.
AB  - Obesity-induced inflammation engenders insulin resistance and type 2 diabetes
      mellitus (T2DM) but the inflammatory effectors linking obesity to insulin
      resistance are incompletely understood. Here, we show that hepatic expression of
      Protein Tyrosine Phosphatase Receptor Gamma (PTPR-gamma) is stimulated by
      inflammation in obese/T2DM mice and positively correlates with indices of
      inflammation and insulin resistance in humans. NF-kappaB binds to the promoter of
      Ptprg and is required for inflammation-induced PTPR-gamma expression. PTPR-gamma
      loss-of-function lowers glycemia and insulinemia by enhancing insulin-stimulated
      suppression of endogenous glucose production. These phenotypes are rescued by re
      expression of Ptprg only in liver of mice lacking Ptprg globally. Hepatic PTPR
      gamma overexpression that mimics levels found in obesity is sufficient to cause
      severe hepatic and systemic insulin resistance. We propose hepatic PTPR-gamma as
      a link between obesity-induced inflammation and insulin resistance and as
      potential target for treatment of T2DM.

PMID- 29180651
TI  - Bidirectional Electron-Transfer in Polypeptides with Various Secondary
      Structures.
AB  - The protein-mediated bidirectional electron transfer (ET) is the foundation of
      protein molecular wire, and plays an important role in the rapid detection of oxo
      guanine-adenine DNA mismatches by MutY glycosylase. However, the influences of
      structural transitions on bidirectional ET are still not clear. In this work, the
      modified through-bond coupling (MTBC) model was further refined to correlate the
      structural transition and ET rate more quantitatively. With this model, various
      polyglycine structures (310-helix, alpha-helix, beta-sheets, linear, polyproline
      helical I and II) were studied to explore the influences of structural
      transitions on bidirectional ET. It was found that the HOMO-LUMO gaps (DeltaE) in
      CN (from the carboxyl to amino terminus) direction are much lower than that in
      opposite direction, except for polypro I. However, with the equal tunneling
      energy, the differences between bidirectional ET rates are slight for all
      structures. In structural transitions, we found that the ET rates are not only
      affected by the Ramachandran angles, but also correlated to the alignment of C =
      O vectors, the alignment of peptide planes and the rearrangement of other
      structure factors. The detailed information can be used to rationalize the
      inhomogeneous ET across different protein structures and design more efficient
      protein molecular wires.

PMID- 29180653
TI  - Prevalence and risk factors of secondhand smoke (SHS) exposure among pregnant
      women in Mongolia.
AB  - This cross-sectional study investigated the prevalence of smoking and secondhand
      smoking (SHS) among pregnant women in Darkhan-Uul Province, Mongolia, using
      urinary cotinine (UC) levels, and clarified the factors related to SHS exposure.
      It targeted pregnant women who underwent antenatal health check-ups from November
      2015 to January 2016. Self-administered questionnaires and urine samples were
      used to collect data. Using UC levels as the criterion, it was found that the
      prevalence of smokers (>100 ng/ml) among 493 pregnant women was 11.8%, while SHS
      exposure (>=5 ng/ml) among nonsmokers was 44.8%. Older and highly educated women
      had lower odds of SHS exposure (p = 0.006 and 0.002, respectively). Furthermore,
      nonsmoking pregnant women from homes where smoking was permitted had higher odds
      of SHS exposure compared to women from homes where smoking was not permitted.
      These results suggest that community guidance programs, such as home smoking
      cessation that include families, are necessary.

PMID- 29180652
TI  - In silico-based screen synergistic drug combinations from herb medicines: a case
      using Cistanche tubulosa.
AB  - Neuroinflammation is characterized by the elaborated inflammatory response
      repertoire of central nervous system tissue. The limitations of the current
      treatments for neuroinflammation are well-known side effects in the clinical
      trials of monotherapy. Drug combination therapies are promising strategies to
      overcome the compensatory mechanisms and off-target effects. However, discovery
      of synergistic drug combinations from herb medicines is rare. Encouraged by the
      successfully applied cases we move on to investigate the effective drug
      combinations based on system pharmacology among compounds from Cistanche tubulosa
      (SCHENK) R. WIGHT. Firstly, 63 potential bioactive compounds, the related 133
      direct and indirect targets are screened out by Drug-likeness evaluation combined
      with drug targeting process. Secondly, Compound-Target network is built to
      acquire the data set for predicting drug combinations. We list the top 10 drug
      combinations which are employed by the algorithm Probability Ensemble Approach
      (PEA), and Compound-Target-Pathway network is then constructed by the 12
      compounds of the combinations, targets, and pathways to unearth the corresponding
      pharmacological actions. Finally, an integrating pathway approach is developed to
      elucidate the therapeutic effects of the herb in different pathological features
      relevant biological processes. Overall, the method may provide a productive
      avenue for developing drug combination therapeutics.

PMID- 29180654
TI  - Ellipsoidal mirror for two-dimensional 100-nm focusing in hard X-ray region.
AB  - Cutting-edge hard X-ray microscopy strongly depends on sophisticated focusing
      optics and ultrabright X-ray sources at synchrotron-radiation and X-ray free
      electron laser (XFEL) facilities. These facilities typically provide two
      dimensional nanofocusing X-ray beams by combining one-dimensional focusing
      mirrors. However, single-reflecting two-dimensional focusing mirrors with an
      ellipsoidal surface, which are well-known to possess high efficiency, have
      limited microfocusing applications. In this paper, we present an ultrahigh
      precision ellipsoidal mirror for two-dimensional X-ray nanofocusing by overcoming
      the difficulties faced in the manufacturing process of its aspherical surface,
      including the surface-processing methods and surface metrology. The developed
      mirror has nanoscale accuracy, and it achieves focus size of 85 nm * 125 nm (full
      width at half maximum) using 7-keV X-rays. Two-dimensional focus was demonstrated
      in the same focal plane by resolving 50-nm test structures by scanning X-ray
      microscopy using a focusing beam. These achievements represent an important first
      step toward realizing two-dimensional aspherical mirrors with complex designs, in
      addition to ultralow loss and unprecedented small focusing property for extensive
      optical applications in synchrotron-radiation and XFEL facilities as well as in
      other scientific fields that require ultraprecision optical surfaces.

PMID- 29180655
TI  - Transition metal binding selectivity in proteins and its correlation with the
      phylogenomic classification of the cation diffusion facilitator protein family.
AB  - Divalent d-block metal cations (DDMCs), such as Fe, Zn and Mn, participate in
      many biological processes. Understanding how specific DDMCs are transported to
      and within the cell and what controls their binding selectivity to different
      proteins is crucial for defining the mechanisms of metalloproteins. To better
      understand such processes, we scanned the RCSB Protein Data Bank, performed a de
      novo structural-based comprehensive analysis of seven DDMCs and found their amino
      acid binding and coordination geometry propensities. We then utilized these
      results to characterize the correlation between metal selectivity, specific
      binding site composition and phylogenetic classification of the cation diffusion
      facilitator (CDF) protein family, a family of DDMC transporters found throughout
      evolution and sharing a conserved structure, yet with different members
      displaying distinct metal selectivity. Our analysis shows that DDMCs differ, at
      times significantly, in terms of their binding propensities, and that in each CDF
      clade, the metal selectivity-related binding site has a unique and conserved
      sequence signature. However, only limited correlation exists between the
      composition of the DDMC binding site in each clade and the metal selectivity
      shown by its proteins.

PMID- 29180656
TI  - Bactofilin-mediated organization of the ParABS chromosome segregation system in
      Myxococcus xanthus.
AB  - In bacteria, homologs of actin, tubulin, and intermediate filament proteins often
      act in concert with bacteria-specific scaffolding proteins to ensure the proper
      arrangement of cellular components. Among the bacteria-specific factors are the
      bactofilins, a widespread family of polymer-forming proteins whose biology is
      poorly investigated. Here, we study the three bactofilins BacNOP in the rod
      shaped bacterium Myxococcus xanthus. We show that BacNOP co-assemble into
      elongated scaffolds that restrain the ParABS chromosome segregation machinery to
      the subpolar regions of the cell. The centromere (parS)-binding protein ParB
      associates with the pole-distal ends of these structures, whereas the DNA
      partitioning ATPase ParA binds along their entire length, using the newly
      identified protein PadC (MXAN_4634) as an adapter. The integrity of these
      complexes is critical for proper nucleoid morphology and chromosome segregation.
      BacNOP thus mediate a previously unknown mechanism of subcellular organization
      that recruits proteins to defined sites within the cytoplasm, far off the cell
      poles.

PMID- 29180657
TI  - The electron-phonon interaction at deep Bi 2 Te3-semiconductor interfaces from
      Brillouin light scattering.
AB  - It is shown that the electron-phonon interaction at a conducting interface
      between a topological insulator thin film and a semiconductor substrate can be
      directly probed by means of high-resolution Brillouin light scattering (BLS). The
      observation of Kohn anomalies in the surface phonon dispersion curves of a 50 nm
      thick Bi2Te3 film on GaAs, besides demonstrating important electron-phonon
      coupling effects in the GHz frequency domain, shows that information on deep
      interface electrons can be obtained by tuning the penetration depth of optically
      generated surface phonons so as to selectively probe the interface region, as in
      a sort of quantum sonar.

PMID- 29180658
TI  - Paleoclimatic information recorded in fluid inclusions in halites from Lop Nur,
      Western China.
AB  - The homogenization temperature (Th) of primary fluid inclusions in halite can be
      used for paleoclimate interpretations. Lop Nur, in Central Asia, is an extremely
      arid zone where large amounts of glauberite were deposited from the late Middle
      to Late Pleistocene. This deposition was accompanied by formation of large-scale
      potash-bearing brines. However, quantitative paleotemperature data are still
      lacking, hindering reconstruction of Quaternary climate conditions and their
      control over potash formation. We measured the Th of inclusions in halite from
      the salt field and the top of Upper Pleistocene strata in Lop Nur. The maximum
      homogenization temperature (Th MAX) of inclusions in halite from the salt field
      was 41.1  degrees C, consistent with the maximum ambient temperature (43.4 
      degrees C) in the same period. The Th MAX of inclusions in halite from the Upper
      Pleistocene strata ranged from 35.6  degrees C to 43  degrees C, where maximum
      air temperatures may have reached 37.9  degrees C to 45.3  degrees C. The results
      show that a hot and arid climate prevailed in Lop Nur at the end of the Late
      Pleistocene. Furthermore, changes of the brine chemical composition due to supply
      variations instead of climate change, may have caused glauberite deposition to
      cease at the end of the Late Pleistocene.

PMID- 29180659
TI  - Cooperative function of Fmp30, Mdm31, and Mdm32 in Ups1-independent cardiolipin
      accumulation in the yeast Saccharomyces cerevisiae.
AB  - Cardiolipin (CL) is synthesized from phosphatidic acid (PA) through a series of
      enzymatic reactions occurring at the mitochondrial inner membrane (MIM). Ups1
      Mdm35 mediates PA transfer from the mitochondrial outer membrane (MOM) to the MIM
      in the yeast Saccharomyces cerevisiae. Deletion of UPS1 leads to a ~80% decrease
      in the cellular CL level. However, the CL accumulation in ups1? cells is enhanced
      by the depletion of Ups2, which forms a protein complex with Mdm35 and mediates
      phosphatidylserine (PS) transfer from the MOM to the MIM for
      phosphatidylethanolamine (PE) synthesis by a PS decarboxylase, Psd1. In this
      study, we found that the accumulation of CL in ups1? cells was enhanced by
      deletion of not only UPS2, but also PSD1 and CHO1 encoding a PS synthase,
      suggesting that low PE levels in mitochondria were relevant to the enhancement of
      CL accumulation in ups1? cells. Furthermore, the Ups1-independent and low-level
      PE-enhanced CL accumulation was shown to depend on the functions of FMP30, MDM31,
      and MDM32. In addition, the physical interactions of Fmp30 with Mdm31 and Mdm32
      were revealed. Thus, when the mitochondrial PE level is reduced, Fmp30, Mdm31,
      and Mdm32 seem to function cooperatively for the accumulation of CL in a UPS1
      independent manner.

PMID- 29180660
TI  - Preparation of ZnS@In2S3 Core@shell Composite for Enhanced Photocatalytic
      Degradation of Gaseous o-Dichlorobenzene under Visible Light.
AB  - In this study, novel ZnS@In2S3 core@shell hollow nanospheres were fabricated by a
      facile refluxing method for the first time, and the formation mechanism of hollow
      structure with interior architecture was discussed based on ion-exchange Ostwald
      ripening. As the photocatalytic material for degradation of gaseous o
      Dichlorobenzene (o-DCB), the as-synthesized core@shell hollow nanospheres were
      found to show significantly enhanced catalytic performance for effective
      separation of photo-generated charges. Moreover, the mechanisms of enhanced
      activity were elucidated by band alignment and unique configuration. Such
      photocatalyst would meet the demands for the control of persistent organic
      pollutant (POPs) in the atmospheric environment.

PMID- 29180661
TI  - Identification of novel genetic loci GAL3ST4 and CHGB involved in susceptibility
      to leprosy.
AB  - Leprosy has long been thought to have a strong genetic component, and so far,
      only positional cloning and genomewide association studies have been used to
      study the genetic susceptibility to leprosy,while whole exome sequencing (WES)
      approach has not yet been applied. In this study, we used WES approach on four
      leprosy patients and four healthy control relatives from two leprosy families. We
      found three new susceptible loci of leprosy, one in GAL3ST4 and two in CHGB. We
      went on to validate the findings of WES using 151 leprosy cases and 226 healthy
      controls by Sanger sequencing. Stratified by gender, GAL3ST4 was found to be the
      susceptible gene only for the female population, and CHGB48 and CHGB23 were
      susceptibile to leprosy for the male population, respectively). Moreover, the
      gene expression levels of the three susceptible loci were measured by real-time
      PCR after the stimulation by M. leprae antigens in the PBMC (peripheral blood
      mononuclear cells) of 69 healthy people. The results showed that the female
      subjects with high frequent genotype in GAL3ST4 had a fivefold elevated
      expression. We suggest the polymorphisms in GAL3ST4 in different population are
      associated with increased risk of leprosy.

PMID- 29180662
TI  - Longer aftershocks duration in extensional tectonic settings.
AB  - Aftershocks number decay through time, depending on several parameters peculiar
      to each seismogenic regions, including mainshock magnitude, crustal rheology, and
      stress changes along the fault. However, the exact role of these parameters in
      controlling the duration of the aftershock sequence is still unknown. Here, using
      two methodologies, we show that the tectonic setting primarily controls the
      duration of aftershocks. On average and for a given mainshock magnitude (1)
      aftershock sequences are longer and (2) the number of earthquakes is greater in
      extensional tectonic settings than in contractional ones. We interpret this
      difference as related to the different type of energy dissipated during
      earthquakes. In detail, (1) a joint effect of gravitational forces and pure
      elastic stress release governs extensional earthquakes, whereas (2) pure elastic
      stress release controls contractional earthquakes. Accordingly, normal faults
      operate in favour of gravity, preserving inertia for a longer period and
      seismicity lasts until gravitational equilibrium is reached. Vice versa, thrusts
      act against gravity, exhaust their inertia faster and the elastic energy
      dissipation is buffered by the gravitational force. Hence, for seismic sequences
      of comparable magnitude and rheological parameters, aftershocks last longer in
      extensional settings because gravity favours the collapse of the hangingwall
      volumes.

PMID- 29180663
TI  - A large and distinct skin impression on the cast of a sauropod dinosaur footprint
      from Early Cretaceous floodplain deposits, Korea.
AB  - The occurrence and features of skin impressions in a sauropod footprint, the
      largest (>50 cm in diameter) reported to date for this taxon, from the Lower
      Cretaceous Haman Formation (Albian) in Korea are described, and its preservation
      and paleoenvironmental implications are interpreted. The skin impression-bearing
      deposits are floodplain sediments formed by sheetflood processes. The large
      impression is preserved in silty mudstone with microbial lenses and wisps
      overlying a planar- to cross-laminated and fine-grained sandstone to siltstone
      bed. The paleoenvironment of the skin impression-bearing deposits is interpreted
      as a saline sandflat to mudflat where microbial mats can form around lakes or
      ponds under semi-arid paleoclimatic conditions with alternating wetting and
      drying intervals. These paleoenvironmental conditions would have permitted the
      distinct preservation of skin impressions in a dinosaur footprint. The
      observations here suggest that some sauropod dinosaurs in the Cretaceous had a
      well-developed polygonal skin texture covering nearly the whole of their foot
      pads, as seen in modern elephants, which would increase stability when walking on
      muddy and wet ground.

PMID- 29180665
TI  - Assessment of Unusual Gigantic Jets observed during the Monsoon season: First
      observations from Indian Subcontinent.
AB  - Gigantic Jets are electric discharges from thunderstorm cloud tops to the bottom
      of ionosphere at ~90 km altitude and electrically connect the troposphere and
      lower ionosphere. Since their first report in 2002, sporadic observations have
      been reported from ground and space based observations. Here we report first
      observations of Gigantic Jets in Indian subcontinent over the Indo-Gangetic
      plains during the monsoon season. Two storms each produced two jets with
      characteristics not documented so far. Jets propagated ~37 km up remarkably in ~5
      ms with velocity of ~7.4 * 106ms-1 and disappeared within ~40-80 ms, which is
      faster compared to jets reported earlier. The electromagnetic signatures show
      that they are of negative polarity, transporting net negative charge of ~17-23 C
      to the lower ionosphere. One jet had an unusual form observed for the first time,
      which emerged from the leading edge of a slowly drifting complex convective cloud
      close to the highest regions at ~17 km altitude. A horizontal displacement of ~10
      km developed at ~50 km altitude before connecting to the lower ionosphere.
      Modeling of these Gigantic jets suggests that Gigantic Jets may bend when
      initiated at the edge of clouds with misaligned vertical charge distribution.

PMID- 29180664
TI  - Circulating microparticles in acute diabetic Charcot foot exhibit a high content
      of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.
AB  - Circulating microparticles (MPs) are major mediators in cardiovascular
      complications of type 2 diabetes (T2D); however, their contribution to Charcot
      foot (CF) disease is not known. Here, we purified and assessed the origin,
      concentration and content of circulating MPs from 33 individuals: 11 with T2D and
      acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic
      controls. First, we demonstrated that there were no differences in the
      distribution of MPs of endothelial, platelet origin among the 3 groups. However,
      MPs from leukocytes and monocytes origin were increased in CF patients. Moreover,
      we demonstrated that monocytes-derived MPs originated more frequently from
      intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF,
      GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute
      CF patients. Applying ingenuity pathways analysis, we found that those cytokines
      interacted well and induced the activation of pathways that are involved in
      osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted
      from healthy patients with CF-derived MPs during their differentiation into
      osteoclasts, which increased their differentiation into multinucleated osteoclast
      like cells. Altogether, our study suggests that circulating MPs in CF disease
      have a high content of inflammatory cytokines and could increase osteoclast
      differentiation in vitro.

PMID- 29180666
TI  - Methane- and dissolved organic carbon-fueled microbial loop supports a tropical
      subterranean estuary ecosystem.
AB  - Subterranean estuaries extend inland into density-stratified coastal carbonate
      aquifers containing a surprising diversity of endemic animals (mostly
      crustaceans) within a highly oligotrophic habitat. How complex ecosystems (termed
      anchialine) thrive in this globally distributed, cryptic environment is poorly
      understood. Here, we demonstrate that a microbial loop shuttles methane and
      dissolved organic carbon (DOC) to higher trophic levels of the anchialine food
      web in the Yucatan Peninsula (Mexico). Methane and DOC production and consumption
      within the coastal groundwater correspond with a microbial community capable of
      methanotrophy, heterotrophy, and chemoautotrophy, based on characterization by
      16S rRNA gene amplicon sequencing and respiratory quinone composition. Fatty acid
      and bulk stable carbon isotope values of cave-adapted shrimp suggest that carbon
      from methanotrophic bacteria comprises 21% of their diet, on average. These
      findings reveal a heretofore unrecognized subterranean methane sink and
      contribute to our understanding of the carbon cycle and ecosystem function of
      karst subterranean estuaries.

PMID- 29180668
TI  - Regulation of human and mouse telomerase genes by genomic contexts and
      transcription factors during embryonic stem cell differentiation.
AB  - Differential regulation of telomerase reverse transcriptase (TERT) genes
      contribute to distinct aging and tumorigenic processes in humans and mice. To
      study TERT regulation, we generated mouse embryonic stem cell (ESC) lines
      containing single-copy bacterial artificial chromosome (BAC) reporters, covering
      hTERT and mTERT genes and their neighboring loci, via recombinase-mediated BAC
      targeting. ESC lines with chimeric BACs, in which two TERT promoters were
      swapped, were also generated. Using these chromatinized BACs, we showed that
      hTERT silencing during differentiation to embryoid bodies (EBs) and to fibroblast
      like cells was driven by the human-specific genomic context and accompanied by
      increases of repressive epigenetic marks, H3K9me3 and H3K27me3, near its
      promoter. Conversely, the mouse genomic context did not repress TERT
      transcription until late during differentiation. The hTERT promoter was more
      active than its mouse counterpart when compared in the same genomic contexts.
      Mutations of E-box and E2F consensus sites at the promoter had little effect on
      hTERT transcription in ESCs. However, the mutant promoters were rapidly silenced
      upon EB differentiation, indicating that transcription factors (TFs) bound to
      these sites were critical in maintaining hTERT transcription during
      differentiation. Together, our study revealed a dynamic hTERT regulation by
      chromatin environment and promoter-bound TFs during ESC differentiation.

PMID- 29180667
TI  - Rods progressively escape saturation to drive visual responses in daylight
      conditions.
AB  - Rod and cone photoreceptors support vision across large light intensity ranges.
      Rods, active under dim illumination, are thought to saturate at higher (photopic)
      irradiances. The extent of rod saturation is not well defined; some studies
      report rod activity well into the photopic range. Using electrophysiological
      recordings from retina and dorsal lateral geniculate nucleus of cone-deficient
      and visually intact mice, we describe stimulus and physiological factors that
      influence photopic rod-driven responses. We find that rod contrast sensitivity is
      initially strongly reduced at high irradiances, but progressively recovers to
      allow responses to moderate contrast stimuli. Surprisingly, rods recover faster
      at higher light levels. A model of rod phototransduction suggests that
      phototransduction gain adjustments and bleaching adaptation underlie rod
      recovery. Consistently, exogenous chromophore reduces rod responses at bright
      background. Thus, bleaching adaptation renders mouse rods responsive to modest
      contrast at any irradiance. Paradoxically, raising irradiance across the photopic
      range increases the robustness of rod responses.

PMID- 29180669
TI  - MYC-containing amplicons in acute myeloid leukemia: Genomic structures,
      evolution, and transcriptional consequences.
AB  - Double minutes (dmin), homogeneously staining regions, and ring chromosomes are
      vehicles of gene amplification in cancer. The underlying mechanism leading to
      their formation as well as their structure and function in acute myeloid leukemia
      (AML) remain mysterious. We combined a range of high-resolution genomic methods
      to investigate the architecture and expression pattern of amplicons involving
      chromosome band 8q24 in 23 cases of AML (AML-amp). This revealed that different
      MYC-dmin architectures can coexist within the same leukemic cell population,
      indicating a step-wise evolution rather than a single event origin, such as
      through chromothripsis. This was supported also by the analysis of the
      chromothripsis criteria, that poorly matched the model in our samples.
      Furthermore, we found that dmin could evolve toward ring chromosomes stabilized
      by neocentromeres. Surprisingly, amplified genes (mainly PVT1) frequently
      participated in fusion transcripts lacking a corresponding DNA template. We also
      detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in
      AML-amp cases versus AML with a normal karyotype. Our results show that 8q24
      amplicons in AML are surprisingly plastic DNA structures with an unexpected
      association to novel fusion transcripts and circular RNAs.Leukemia accepted
      article preview online, 28 November 2017. doi:10.1038/leu.2017.337.

PMID- 29180671
TI  - Corticostriatal circuit defects in Hoxb8 mutant mice.
AB  - This corrects the article DOI: 10.1038/mp.2017.180.

PMID- 29180670
TI  - MiR-16-5p mediates a positive feedback loop in EV71-induced apoptosis and
      suppresses virus replication.
AB  - Enterovirus 71 (EV71) is the predominant causative pathogen of hand-foot-and
      mouth disease (HFMD). Contrary to other HFMD-causing enterovirus, EV71 can lead
      to severe neurological complications, even death. MicroRNAs (miRNAs) are small
      non-coding RNAs that constitute the largest family of gene regulators
      participating in numerous biological or pathological processes. We previously
      reported that miR-16-5p increases with severity of HFMD by investigating the
      expression patterns of host miRNAs in patients with HFMD. However, the mechanisms
      by which EV71 induces miR-16-5p expression are not clear, and the interaction
      between EV71 and miR-16-5p is not yet fully understood. Here, we confirmed EV71
      induced expression of miR-16-5p both in vitro and in vivo and show that
      upregulation of miR-16-5p by EV71 infection may occur at the posttranscriptional
      level. Moreover, EV71-induced caspase activation facilitates the processing of
      pri-miR-16-1. We also revealed that miR-16-5p can promote EV71-induced nerve
      cells apoptosis through activating caspase-3. In addition, we found that miR-16
      5p can inhibit EV71 replication. CCNE1 and CCND1, two important cell cycle
      regulators, play an important role in the suppression of EV71 replication by miR
      16-5p. Therefore, miR-16-5p is a positive feedback regulator in EV71-induced
      apoptosis and a suppressor of virus replication. These results help in
      understanding the interaction network between miRNA and EV71 infection and
      provide a potential target for the development of antiviral therapy.

PMID- 29180674
TI  - Why is there selective subcortical vulnerability in ADHD? Clues from postmortem
      brain gene expression data.
AB  - Sub-cortical volumetric differences were associated with attention
      deficit/hyperactivity disorder (ADHD) in a recent multi-site, mega-analysis of
      1713 ADHD persons and 1529 controls. As there was a wide range of effect sizes
      among the sub-cortical volumes, it is possible that selective neuronal
      vulnerability has a role in these volumetric losses. To address this possibility,
      we used data from Allen Brain Atlas to investigate variability in gene expression
      profiles between subcortical regions of typically developing brains. We tested
      the hypothesis that the expression of genes in a set of curated ADHD candidate
      genes and five a priori selected, biological pathways would be associated with
      the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) findings.
      Across the subcortical regions studied by ENIGMA, gene expression profiles for
      three pathways were significantly correlated with ADHD-associated volumetric
      reductions: apoptosis, oxidative stress and autophagy. These correlations were
      strong and significant for children with ADHD, but not for adults. Although
      preliminary, these data suggest that variability of structural brain anomalies in
      ADHD can be explained, in part, by the differential vulnerability of these
      regions to mechanisms mediating apoptosis, oxidative stress and autophagy.

PMID- 29180673
TI  - Calhm2 governs astrocytic ATP releasing in the development of depression-like
      behaviors.
AB  - Extracellular ATP is a widespread cell-to-cell signaling molecule in the brain,
      where it functions as a neuromodulator by activating glia and neurons. Although
      ATP exerts multiple effects on synaptic plasticity and neuro-glia interactions,
      as well as in mood disorders, the source and regulation of ATP release remain to
      be elaborated. Here, we define Calhm2 as an ATP-releasing channel protein based
      on in vitro and in vivo models. Conventional knockout and conditional astrocyte
      knockout of Calhm2 both lead to significantly reduced ATP concentrations, loss of
      hippocampal spine number, neural dysfunction and depression-like behaviors in
      mice, which can be significantly rescued by ATP replenishment. Our findings
      identify Calhm2 as a critical ATP-releasing channel that modulates neural
      activity and as a potential risk factor of depression.

PMID- 29180672
TI  - The thalamic reticular nucleus in schizophrenia and bipolar disorder: role of
      parvalbumin-expressing neuron networks and oxidative stress.
AB  - Growing evidence points to a disruption of cortico-thalamo-cortical circuits in
      schizophrenia (SZ) and bipolar disorder (BD). Clues for a specific involvement of
      the thalamic reticular nucleus (TRN) come from its unique neuronal
      characteristics and neural connectivity, allowing it to shape the thalamo
      cortical information flow. A direct involvement of the TRN in SZ and BD has not
      been tested thus far. We used a combination of human postmortem and rodent
      studies to test the hypothesis that neurons expressing parvalbumin (PV neurons),
      a main TRN neuronal population, and associated Wisteria floribunda agglutinin
      labeled perineuronal nets (WFA/PNNs) are altered in SZ and BD, and that these
      changes may occur early in the course of the disease as a consequence of
      oxidative stress. In both disease groups, marked decreases of PV neurons
      (immunoreactive for PV) and WFA/PNNs were observed in the TRN, with no effects of
      duration of illness or age at onset. Similarly, in transgenic mice with redox
      dysregulation, numbers of PV neurons and WFA/PNN+PV neurons were decreased in
      transgenic compared with wild-type mice; these changes were present at postnatal
      day (P) 20 for PV neurons and P40 for WFA/PNN+PV neurons, accompanied by
      alterations of their firing properties. These results show profound abnormalities
      of PV neurons in the TRN of subjects with SZ and BD, and offer support for the
      hypothesis that oxidative stress may play a key role in impacting TRN PV neurons
      at early stages of these disorders. We put forth that these TRN abnormalities may
      contribute to disruptions of sleep spindles, focused attention and emotion
      processing in these disorders.

PMID- 29180675
TI  - Protein kinase Mzeta in medial prefrontal cortex mediates depressive-like
      behavior and antidepressant response.
AB  - Neuronal atrophy and alterations of synaptic structure and function in the medial
      prefrontal cortex (mPFC) have been implicated in the pathogenesis of depression,
      but the underlying molecular mechanisms are largely unknown. The protein kinase
      Mzeta (PKMzeta), a brain-specific atypical protein kinase C isoform, is important
      for maintaining long-term potentiation and storing memory. In the present study,
      we explored the role of PKMzeta in mPFC in two rat models of depression, chronic
      unpredictable stress (CUS) and learned helplessness. The involvement of PKMzeta
      in the antidepressant effects of conventional antidepressants and ketamine were
      also investigated. We found that chronic stress decreased the expression of
      PKMzeta in the mPFC and hippocampus but not in the orbitofrontal cortex.
      Overexpression of PKMzeta in mPFC prevented the depressive-like and anxiety-like
      behaviors induced by CUS, and reversed helplessness behaviors. Inhibition of
      PKMzeta in mPFC by expressing a PKMzeta dominant-negative mutant induced
      depressive-like behaviors after subthreshold unpredictable stress and increased
      learned helplessness behavior. Furthermore, stress-induced deficits in synaptic
      proteins and decreases in dendritic density and the frequency of miniature
      excitatory postsynaptic currents in the mPFC were prevented by PKMzeta
      overexpression and potentiated by PKMzeta inhibition in subthreshold stress rats.
      The antidepressants fluoxetine, desipramine and ketamine increased PKMzeta
      expression in mPFC and PKMzeta mediated the antidepressant effects of ketamine.
      These findings identify PKMzeta in mPFC as a critical mediator of depressive-like
      behavior and antidepressant response, providing a potential therapeutic target in
      developing novel antidepressants.

PMID- 29180676
TI  - Greatly enhanced light emission of MoS2 using photonic crystal heterojunction.
AB  - We present theoretical study on developing a one-dimensional (1D) photonic
      crystal heterojunction (h-PhC) that consists of a monolayer molybdenum disulfide
      (MoS2) structure. By employing the transfer matrix method, we obtained the
      analytical solution of the light absorption and emission of two-dimensional
      materials in 1D h-PhC. Simultaneously enhancing the light absorption and emission
      of the medium in multiple frequency ranges is easy as h-PhC has more modes of
      photon localization than the common photonic crystal. Our numerical results
      demonstrate that the proposed 1D h-PhC can simultaneously enhance the light
      absorption and emission of MoS2 and enhance the photoluminescence spectrum of
      MoS2 by 2-3 orders of magnitude.

PMID- 29180677
TI  - Toughness amplification in copper/epoxy joints through pulsed laser micro
      machined interface heterogeneities.
AB  - This work addresses the mechanics of debonding along copper/epoxy joints
      featuring patterned interfaces. Engineered surface heterogeneities with enhanced
      adhesion properties are generated through pulsed laser irradiation. Peel tests
      are carried out to ascertain the effect of patterns shape and area fraction on
      the mechanical response. Experimental results are evaluated with the support of
      three-dimensional finite element simulations based on the use of cohesive
      surfaces. Results discussion is largely framed in terms of effective peel force
      and energy absorbed to sever the samples. It is shown that surface
      heterogeneities act as sites of potential crack pinning able to trigger crack
      initiation, propagation and arrest. Surface patterns ultimately enable a
      remarkable increase in the effective peel force and dissipated energy with
      respect to baseline homogeneous sanded interface.

PMID- 29180678
TI  - Long non-coding RNA LINC00152 promotes cell proliferation, metastasis, and
      confers 5-FU resistance in colorectal cancer by inhibiting miR-139-5p.
AB  - Long intergenic non-coding RNA 152 (LINC00152) is a recently identified tumor
      promoting long non-coding RNA. However, the biological functions of LINC00152 in
      colorectal cancer (CRC) remain unclear and require further research. The aim of
      the present study is to explore the roles of LINC00152 in cellular function and
      its possible molecular mechanism. In this study, we discovered that LINC00152 was
      overexpressed in CRC tissues and negatively related to the survival time of CRC
      patients. Functional analyses revealed that LINC00152 could promote cell
      proliferation. Furthermore, LINC00152 could increase the resistance of CRC cells
      to 5-fluorouracil (5-FU) by suppressing apoptosis. We also discovered that
      LINC00152 could enhance cell migration and invasion. Mechanistic studies
      demonstrated that LINC00152 could regulate the expression of NOTCH1 through
      sponging miR-139-5p and inhibiting its activity from promoting CRC progression
      and development. Altogether, our work points out a novel LINC00152/miR-139
      5p/NOTCH1 regulatory axis in CRC progression and development.

PMID- 29180679
TI  - Risk of non-cardiac surgery after percutaneous coronary intervention with drug
      eluting stents.
AB  - Elective non-cardiac surgery (NCS) should optimally be delayed one year after
      implantation of a drug-eluting stent (DES). Dual antiplatelet therapy or at least
      aspirin is recommended to be continued considering the relative risk of stent
      thrombosis especially during the 4 weeks after DES implantation. However, these
      recommendations were supported by insufficient evidence. We investigated
      predictors for postoperative major adverse cardiovascular and cerebral event
      (MACCE) in 1582 patients undergoing non-cardiac surgery after DES implantation.
      96 patients (6.1%) developed postoperative MACCE. In the propensity score-matched
      analysis, aspirin maintenance was not associated with MACCE (odds ratio [OR]
      0.78, 95% confidence interval [CI] 0.48-1.27, P = 0.320) and was associated with
      increased risk of major bleeding (OR 1.84, 95% CI 1.02-3.32, P = 0.044). When
      patients who underwent NCS within one month after DES implantation were matched
      with those who underwent NCS thereafter, the risk of MACCE was higher when
      surgery was done within 30 days after PCI (OR 2.21, 95% CI 1.05-4.66, P = 0.036).
      Maintenance of aspirin did not decrease MACCE after NCS in patients with DES and
      only increased the risk of major bleeding. NCS within one month after DES
      implantation was associated with higher incidence of MACCE. However, prospective
      trials are required to validate our results.

PMID- 29180680
TI  - Functional interplay between the transcription factors USF1 and PDX-1 and protein
      kinase CK2 in pancreatic beta-cells.
AB  - Glucose homeostasis is regulated by insulin, which is produced in the beta-cells
      of the pancreas. The synthesis of insulin is controlled by several transcription
      factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as
      substrates for protein kinase CK2. Here, we have analysed the interplay of PDX-1,
      USF1 and CK2 in the regulation of PDX-1 gene transcription. We found that the PDX
      1 promoter is dose-dependently transactivated by PDX-1 and transrepressed by
      USF1. With increasing glucose concentrations the transrepression of the PDX-1
      promoter by USF1 is successively abrogated. PDX-1 binding to its own promoter was
      not influenced by glucose, whereas USF1 binding to the PDX-1 promoter was
      reduced. The same effect was observed after inhibition of the protein kinase
      activity by three different inhibitors or by using a phospho-mutant of USF1.
      Moreover, phosphorylation of USF1 by CK2 seems to strengthen the interaction
      between USF1 and PDX-1. Thus, CK2 is a negative regulator of the USF1-dependent
      PDX-1 transcription. Moreover, upon inhibition of CK2 in primary islets, insulin
      expression as well as insulin secretion were enhanced without affecting the
      viability of the cells. Therefore, inhibition of CK2 activity may be a promising
      approach to stimulate insulin production in pancreatic beta-cells.

PMID- 29180681
TI  - Subthalamic Nucleus Deep Brain Stimulation Does Not Modify the Functional
      Deficits or Axonopathy Induced by Nigrostriatal alpha-Synuclein Overexpression.
AB  - Subthalamic nucleus deep brain stimulation (STN DBS) protects dopaminergic
      neurons of the substantia nigra pars compacta (SNpc) against 6-OHDA and MPTP. We
      evaluated STN DBS in a parkinsonian model that displays alpha-synuclein pathology
      using unilateral, intranigral injections of recombinant adeno-associated virus
      pseudotype 2/5 to overexpress wildtype human alpha-synuclein (rAAV2/5 alpha-syn).
      A low titer of rAAV2/5 alpha-syn results in progressive forelimb asymmetry, loss
      of striatal dopaminergic terminal density and modest loss of SNpc dopamine
      neurons after eight weeks, corresponding to robust human-Snca expression and no
      effect on rat-Snca, Th, Bdnf or Trk2. alpha-syn overexpression increased
      phosphorylation of ribosomal protein S6 (p-rpS6) in SNpc neurons, a readout of
      trkB activation. Rats received intranigral injections of rAAV2/5 alpha-syn and
      three weeks later received four weeks of STN DBS or electrode implantation that
      remained inactive. STN DBS did not protect against alpha-syn-mediated deficits in
      forelimb akinesia, striatal denervation or loss of SNpc neuron, nor did STN DBS
      elevate p-rpS6 levels further. ON stimulation, forelimb asymmetry was
      exacerbated, indicating alpha-syn overexpression-mediated neurotransmission
      deficits. These results demonstrate that STN DBS does not protect the
      nigrostriatal system against alpha-syn overexpression-mediated toxicity. Whether
      STN DBS can be protective in other models of synucleinopathy is unknown.

PMID- 29180682
TI  - Features of reactive cysteines discovered through computation: from kinase
      inhibition to enrichment around protein degrons.
AB  - Large-scale characterisation of cysteine modification is enabling study of the
      physicochemical determinants of reactivity. We find that location of cysteine at
      the amino terminus of an alpha-helix, associated with activity in thioredoxins,
      is under-represented in human protein structures, perhaps indicative of selection
      against background reactivity. An amino-terminal helix location underpins the
      covalent linkage for one class of kinase inhibitors. Cysteine targets for S
      palmitoylation, S-glutathionylation, and S-nitrosylation show little correlation
      with pKa values predicted from structures, although flanking sequences of S
      palmitoylated sites are enriched in positively-charged amino acids, which could
      facilitate palmitoyl group transfer to substrate cysteine. A surprisingly large
      fraction of modified sites, across the three modifications, would be buried in
      native protein structure. Furthermore, modified cysteines are (on average) closer
      to lysine ubiquitinations than are unmodified cysteines, indicating that cysteine
      redox biology could be associated with protein degradation and degron
      recognition.

PMID- 29180683
TI  - Hydrogen gas mediates ascorbic acid accumulation and antioxidant system
      enhancement in soybean sprouts under UV-A irradiation.
AB  - The soybean sprout is a nutritious and delicious vegetable that is rich in
      ascorbic acid (AsA). Hydrogen gas (H2) may have potential applications in the
      vegetable processing industry. To investigate whether H2 is involved in the
      regulation of soybean sprouts AsA biosynthesis under UV irradiation, we set 4
      different treatments: white light(W), W+HRW, UV-A and UV-A+HRW. The results
      showed that H2 significantly blocked the UV-A-induced accumulation of ROS,
      decreased TBARS content and enhanced SOD and APX activity in soybean sprouts. We
      also observed that the UV-A induced accumulation of AsA was enhanced more
      intensely when co-treated with HRW. Molecular analyses showed that UV-A+HRW
      significantly up-regulated AsA biosynthesis and recycling genes compared to UV-A
      in soybean sprouts. These data demonstrate that the H2 positively regulates
      soybean sprouts AsA accumulation under UV-A and that this effect is mediated via
      the up-regulation of AsA biosynthesis and recycling genes.

PMID- 29180684
TI  - Systemic clearance and brain distribution of carbazole-based cyanine compounds as
      Alzheimer's disease drug candidates.
AB  - SLM and SLOH, two analogues of carbazole-based cyanine compounds, have been shown
      to inhibit beta-amyloid peptide aggregation in vitro and in Alzheimer's disease
      model mice, which could be potentially developed into drugs for disease
      treatment. To pave the way for further pharmacokinetics-pharmacodynamics study,
      we set to investigate these compounds' systemic clearance pathways and their
      brain exposure. We found that they generally exhibited relatively low plasma
      clearance which comprised of hepatic clearance and biliary clearance. Phase I
      oxidative metabolites for SLM and for SLOH upon microsomes incubation were
      identified, and the metabolism by CYP3A4 were found to be the major (>70%)
      hepatic clearance pathway, while the efflux by P-gp and BCRP located in the
      canalicular membrane of hepatocytes led to high biliary clearance. The permeation
      of SLM and SLOH through the brain endothelium was affected by the efflux
      transporters (P-gp and BCRP) and influx transporter (OATP2B1). The unbound
      interstitial fluid to plasma ratio (K puu,brain) was 8.10 for SLOH and 11.0 for
      SLM, which favored brain entry and were several folds higher than that in wild
      type mice. Taken together, these carbazole compounds displayed low plasma
      clearance and high brain permeability, which entitle further development.

PMID- 29180685
TI  - Evaluating the effect of Clostridium difficile conditioned medium on fecal
      microbiota community structure.
AB  - Clostridium difficile infection (CDI) is typically associated with disturbed gut
      microbiota and changes related to decreased colonization resistance against C.
      difficile are well described. However, nothing is known about possible effects of
      C. difficile on gut microbiota restoration during or after CDI. In this study, we
      have mimicked such a situation by using C. difficile conditioned medium of six
      different C. difficile strains belonging to PCR ribotypes 027 and 014/020 for
      cultivation of fecal microbiota. A marked decrease of microbial diversity was
      observed in conditioned medium of both tested ribotypes. The majority of
      differences occurred within the phylum Firmicutes, with a general decrease of gut
      commensals with putative protective functions (i.e. Lactobacillus,
      Clostridium_XIVa) and an increase in opportunistic pathogens (i.e. Enterococcus).
      Bacterial populations in conditioned medium differed between the two C. difficile
      ribotypes, 027 and 014/020 and are likely associated with nutrient availability.
      Fecal microbiota cultivated in medium conditioned by E. coli, Salmonella
      Enteritidis or Staphylococcus epidermidis grouped together and was clearly
      different from microbiota cultivated in C. difficile conditioned medium
      suggesting that C. difficile effects are specific. Our results show that the
      changes observed in microbiota of CDI patients are partially directly influenced
      by C. difficile.

PMID- 29180686
TI  - Immobilized Cerrena sp. laccase: preparation, thermal inactivation, and
      operational stability in malachite green decolorization.
AB  - Laccases are polyphenol oxidases with widespread applications in various
      industries. In the present study, the laccase from Cerrena sp. HYB07 was
      immobilized with four methods, namely entrapment in alginate, covalently binding
      to chitosan as well as formation of cross-linked enzyme aggregates (CLEAs) and
      magnetic CLEAs (M-CLEAs). The activity recovery rates of the immobilized laccases
      ranged from 29% to 68%. Immobilization elevated the reaction temperature optimum
      and reduced substrate specificity, but not necessarily the turnover rate. pH
      stability of immobilized laccases was improved compared with that of the free
      laccase, especially at acidic pH values. Thermal inactivation of all laccases
      followed a simple first-order exponential decay model, and immobilized laccases
      displayed higher thermostability, as manifested by lower thermal inactivation
      rate constants and longer enzyme half-life time. Operational stability of the
      immobilized laccase was demonstrated by decolorization of the triphenylmethane
      dye malachite green (MG) at 60  degrees C. MG decolorization with free laccase
      was accompanied by a shift of the absorption peak and accumulation of a stable,
      colored intermediate tetradesmethyl MG, probably due to lower thermostability of
      the free laccase and premature termination of the degradation pathway. In
      contrast, complete decolorization of MG was achieved with laccase CLEAs at 60 
      degrees C.

PMID- 29180687
TI  - Exploring Voluntary Vaccinating Behaviors using Evolutionary N-person Threshold
      Games.
AB  - Understanding individuals' voluntary vaccinating behaviors plays essential roles
      in making vaccination policies for many vaccinepreventable diseases. Usually,
      individuals decide whether to vaccinate through evaluating the relative cost of
      vaccination and infection according to their own interests. Mounting evidence
      shows that the best vaccine coverage level for the population as a whole can
      hardly be achieved due to the effects of herd immunity. In this paper, taking
      into consideration the herd immunity threshold, we present an evolutionary N
      person threshold game, where individuals can dynamically adjust their vaccinating
      strategies and their payoffs depend nonlinearly on whether or not the herd
      immunity threshold is reached. First, in well-mixed populations, we analyze the
      relationships at equilibrium among the fraction of vaccinated individuals, the
      population size, the basic reproduction number and the relative cost of
      vaccination and infection. Then, we carry out simulations on four types of
      complex networks to explore the evolutionary dynamics of the N-person threshold
      game in structured populations. Specifically, we investigate the effects of
      disease severity and population structure on the vaccine coverage for different
      relative costs of vaccination and infection. The results and findings can offer
      new insight into designing incentive-based vaccination policies for disease
      intervention and control.

PMID- 29180689
TI  - A new A-P compartment boundary and organizer in holometabolous insect wings.
AB  - Decades of research on the highly modified wings of Drosophila melanogaster has
      suggested that insect wings are divided into two Anterior-Posterior (A-P)
      compartments separated by an axis of symmetry. This axis of symmetry is created
      by a developmental organizer that establishes symmetrical patterns of gene
      expression that in turn pattern the A-P axis of the wing. Butterflies possess
      more typical insect wings and butterfly wing colour patterns provide many
      landmarks for studies of wing structure and development. Using eyespot colour
      pattern variation in Vanessa butterflies, here we show an additional A-P axis of
      symmetry running between wing sectors 3 and 4. Boundaries of Drosophila mitotic
      clones suggest the existence of a previously undetected Far-Posterior (F-P)
      compartment boundary that coincides with this additional A-P axis. A similar
      compartment boundary is evident in butterfly mosaic gynandromorphs. We suggest
      that this additional compartment boundary and its associated developmental
      organizer create an axis of wing colour pattern symmetry and a gene expression
      based combinatorial code, permitting each insect wing compartment to acquire a
      unique identity and allowing for the individuation of butterfly eyespots.

PMID- 29180688
TI  - Involvement of cecropin B in the formation of the Aedes aegypti mosquito cuticle.
AB  - In this study, we found a mosquito antimicrobial peptide (AMP), Aedes aegypti
      cecropin B (Aacec B), was expressed constitutively in pupae. Knockdown in the
      pupae of Aacec B using double-stranded RNA (dsRNA) resulted in high mortality,
      the emergence of deformed adults and an impairment of pharate adult cuticle
      formation with fewer lamellae being deposited and the helicoidal pattern of the
      chitin microfibrils being disorganized. Simultaneous injection of Aacec B dsRNA
      and Aacec B peptide into pupae significantly reduced this mortality and no
      deformed adults then emerged. The expression levels of Ae. aegypti
      prophenoloxidase (AaPPO) 3 and AaPPO 4 were significantly reduced in the Aacec B
      knockdown pupae. Exogenous Aacec B peptide significantly enhanced the
      transcription of AaPPO 3 in pupae. Knockdown of AaPPO 3 in pupae caused effects
      similar to Aacec B-knockdown. The Aacec B peptide could be detected in both the
      cytoplasm and nuclei of pupal cells and was able to bind to the TTGG(A/C)A motif
      in AaPPO 3 DNA both in vitro and in vivo. These findings suggest that Aacec B
      plays a crucial role in pharate adult cuticle formation via the regulation of
      AaPPO 3 gene expression in pupae.

PMID- 29180691
TI  - Serum Uric Acid is Independently Associated with Enlarged Perivascular Spaces.
AB  - Enlarged perivascular spaces (EPVS) are reported to be associated with impaired
      cognitive function and sleep disorders. It is of clinical importance to
      understand the risk factors for EPVS. Hyperuricemia increases the risk of
      hypertension and endothelial dysfunction, which are well recognized to be
      associated with EPVS. Therefore, we postulated that serum uric acid (SUA) might
      be associated with EPVS. A total of 665 lacunar stroke patients were enrolled in
      this study. The SUA concentrations of patients with severe EPVS were much higher
      than those of patients with mild EPVS (for basal ganglia: 5.25 +/- 1.40 mg/dl vs.
      4.75 +/- 1.40 mg/dl, p < 0.001; for white matter: 5.31 +/- 1.41 mg/dl vs. 4.88 +/
      1.37 mg/dl, p = 0.009). The percentage of subjects with severe EPVS tended to be
      higher in the highest quartile of SUA (chi-square test: P = 0.002 for basal
      ganglia and 0.006 for white matter). Spearman correlation analysis indicated that
      the SUA concentrations were positively correlated with the severity of EPVS (rho
      > 0, p < 0.05). Multivariate logistic regression analysis showed that high normal
      SUA was independently associated with a higher severity of EPVS. This finding
      suggests that high SUA levels might be an independent risk factor for EPVS in
      lacunar stroke patients.

PMID- 29180690
TI  - FAD104, a regulator of adipogenesis, is a novel suppressor of TGF-beta-mediated
      EMT in cervical cancer cells.
AB  - Epithelial-to-mesenchymal transition (EMT) is a biological process in which
      epithelial cells translate into a mesenchymal phenotype with invasive capacities,
      contributing to tumour progression, metastasis, and the acquisition of
      chemotherapy resistance. To identify new therapeutic targets for cancers, it is
      important to clarify the molecular mechanism of induction of EMT. We have
      previously reported that fad104, a positive regulator of adipocyte
      differentiation, suppressed the invasion and metastasis of melanoma and breast
      cancer cells. In this study, we showed that FAD104 functions as a novel
      suppressor of transforming growth factor-beta (TGF-beta)-mediated EMT in cervical
      cancer cells. Expression of FAD104 is upregulated during TGF-beta-mediated EMT in
      human cervical cancer HeLa cells. Reduction of fad104 expression enhanced TGF
      beta-mediated EMT and migration in HeLa cells. Conversely, overexpression of
      FAD104 suppressed TGF-beta-induced EMT. In addition, we showed that FAD104
      negatively regulated phosphorylation of Smad2 and Smad3 but positively regulated
      phosphorylation of Smad1/5/8 via treatment with TGF-beta. These findings
      demonstrate that FAD104 is a novel suppressor of TGF-beta signalling and
      represses TGF-beta-mediated EMT in cervical cancer cells.

PMID- 29180692
TI  - Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling
      cascade and NLRP3 inflammasome activation in mice.
AB  - Baicalein (5,6,7-trihydroxyflavone), a predominant bioactive component isolated
      from the root of Scutellaria baicalensis Georgi, has established potent anti
      inflammatory activity via multi-targeted mechanisms. However, little is known
      about the effect of baicalein on 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      induced colitis, which shares pathology related to human Crohn's disease (CD).
      The present study demonstrated that baicalein alleviated the severity of TNBS
      induced colitis in mice by decreasing the activity of myeloperoxidase (MPO) and
      the expression of pro-inflammatory mediators. The decline in the activation of
      nuclear factor-kappa B (NF-kappaB) and p38 mitogen-activated protein kinase
      (MAPK) correlated with a decrease in the expression of mucosal toll-like receptor
      4 (TLR4) and its adaptor myeloid differentiation factor 88 (MyD88). In vitro,
      baicalein down-regulated the TLR4/MyD88 signaling cascades (NF-kappaB and MAPKs)
      in lipopolysaccharide (LPS)-stimulated macrophages. At the upstream level,
      baicalein bound to the hydrophobic region of the myeloid differentiation protein
      2 (MD-2) pocket and inhibited the formation of the LPS-induced MD-2/TLR4 complex.
      Furthermore, baicalein reduced NOD-like receptor 3 (NLRP3) inflammasome
      activation and downstream interleukin-1beta expression in a dose-dependent
      manner. Our study provided evidence for the first time that baicalein attenuated
      TNBS-induced colitis, at least in part, via inhibition of TLR4/MyD88 signaling
      cascade as well as inactivation of NLRP3 inflammasome.

PMID- 29180693
TI  - Anomalous Growth Rate of Ag Nanocrystals Revealed by in situ STEM.
AB  - In situ microscopy of colloidal nanocrystal growth offers a unique opportunity to
      acquire direct and straightforward data for assessing classical growth models.
      Here, we observe the growth trajectories of individual Ag nanoparticles in
      solution using in situ scanning transmission electron microscopy. For the first
      time, we provide experimental evidence of growth rates of Ag nanoparticles in the
      presence of Pt in solution that are significantly faster than predicted by
      Lifshitz-Slyozov-Wagner theory. We attribute these observed anomalous growth
      rates to the synergistic effects of the catalytic properties of Pt and the
      electron beam itself. Transiently reduced Pt atoms serve as active sites for Ag
      ions to grow, thereby playing a key role in controlling the growth kinetics.
      Electron beam illumination greatly increases the local concentration of free
      radicals, thereby strongly influencing particle growth rate and the resulting
      particle morphology. Through a systematic investigation, we demonstrate the
      feasibility of utilizing these synergistic effects for controlling the growth
      rates and particle morphologies at the nanoscale. Our findings not only expand
      the current scope of crystal growth theory, but may also lead to a broader
      scientific application of nanocrystal synthesis.

PMID- 29180694
TI  - Anions for Near-Infrared Selective Organic Salt Photovoltaics.
AB  - Organic molecular salts are an emerging and highly tunable class of materials for
      organic and transparent photovoltaics. In this work, we demonstrate novel phenyl
      borate and carborane-based anions paired with a near-infrared (NIR)-selective
      heptamethine cation. We further explore the effects of anion structures and
      functional groups on both device performance and physical properties. Changing
      the functional groups on the anion significantly alters the open circuit voltage
      and yields a clear dependence on electron withdrawing groups. Anion exchange is
      also shown to selectively alter the solubility and film surface energy of the
      resulting molecular salt, enabling the potential fabrication of solution
      deposited cascade or multi-junction devices from orthogonal solvents. This study
      further expands the catalog and properties of organic salts for inexpensive, and
      stable NIR-selective molecular salt photovoltaics.

PMID- 29180695
TI  - The interactive effects of arbuscular mycorrhiza and plant growth-promoting
      rhizobacteria synergistically enhance host plant defences against pathogens.
AB  - Belowground interactions between plant roots, mycorrhizal fungi and plant growth
      promoting rhizobacteria (PGPR) can improve plant health via enhanced nutrient
      acquisition and priming of the plant immune system. Two wheat cultivars differing
      in their ability to form mycorrhiza were (co)inoculated with the mycorrhizal
      fungus Rhizophagus irregularis and the rhizobacterial strain Pseudomonas putida
      KT2440. The cultivar with high mycorrhizal compatibility supported higher levels
      of rhizobacterial colonization than the low compatibility cultivar. Those levels
      were augmented by mycorrhizal infection. Conversely, rhizobacterial colonization
      of the low compatibility cultivar was reduced by mycorrhizal arbuscule formation.
      Single inoculations with R. irregularis or P. putida had differential growth
      effects on both cultivars. Furthermore, while both cultivars developed systemic
      priming of chitosan-induced callose after single inoculations with R. irregularis
      or P. putida, only the cultivar with high mycorrhizal compatibility showed a
      synergistic increase in callose responsiveness following co-inoculation with both
      microbes. Our results show that multilateral interactions between roots,
      mycorrhizal fungi and PGPR can have synergistic effects on growth and systemic
      priming of wheat.

PMID- 29180696
TI  - Stanene-hexagonal boron nitride heterobilayer: Structure and characterization of
      electronic property.
AB  - The structural and electronic properties of stanene/hexagonal boron nitride (Sn/h
      BN) heterobilayer with different stacking patterns are studied using first
      principle calculations within the framework of density functional theory. The
      electronic band structure of different stacking patterns shows a direct band gap
      of ~30 meV at Dirac point and at the Fermi energy level with a Fermi velocity of
      ~0.53 * 106 ms-1. Linear Dirac dispersion relation is nearly preserved and the
      calculated small effective mass in the order of 0.05mo suggests high carrier
      mobility. Density of states and space charge distribution of the considered
      heterobilayer structure near the conduction and the valence bands show
      unsaturated pi orbitals of stanene. This indicates that electronic carriers are
      expected to transport only through the stanene layer, thereby leaving the h-BN
      layer to be a good choice as a substrate for the heterostructure. We have also
      explored the modulation of the obtained band gap by changing the interlayer
      spacing between h-BN and Sn layer and by applying tensile biaxial strain to the
      heterostructure. A small increase in the band gap is observed with the increasing
      percentage of strain. Our results suggest that, Sn/h-BN heterostructure can be a
      potential candidate for Sn-based nanoelectronics and spintronic applications.

PMID- 29180697
TI  - Resistance mutations of Pro197, Asp376 and Trp574 in the acetohydroxyacid
      synthase (AHAS) affect pigments, growths, and competitiveness of Descurainia
      sophia L.
AB  - D. Sophia is one of the most problematic weed species infesting winter wheat in
      China, and has evolved high resistance to tribenuron-methyl. Amino acid
      substitutions at site of Pro197, Asp376 and Trp574 in acetohydroxyacid synthase
      (AHAS) were mainly responsible for D. sophia resistance to tribenuron-methyl. In
      this study, D. sophia plant individually homozygous for specific AHAS mutation
      (Pro197Leu, Pro197His, Pro197Ser, Pro197Thr, Asp376Glu and Trp574Leu) were
      generated. In addition, the effects of resistance mutations on pigments, growths
      and competitiveness of susceptible (S) and resistant (R) plants of D. sophia were
      investigated. The results indicated the R plants carrying Pro197Leu or Pro197His
      or Asp376Glu or Trp574Leu displayed stronger competitiveness than S plants. The
      adverse effects on R plants aggravated with the increase of R plants proportion,
      which made the R plants against domination the weed community in absent of
      herbicide selection. Therefore, these resistance mutation have no obvious adverse
      effects on the pigments (chlorophyll a, chlorophyll b and carotenoid), relative
      growth rates (RGR), leaf area ratio (LAR) and net assimilation rate (NAR) of R
      plants.

PMID- 29180698
TI  - Dual impact of elevated temperature on plant defence and bacterial virulence in
      Arabidopsis.
AB  - Environmental conditions profoundly affect plant disease development; however,
      the underlying molecular bases are not well understood. Here we show that
      elevated temperature significantly increases the susceptibility of Arabidopsis to
      Pseudomonas syringae pv. tomato (Pst) DC3000 independently of the phyB/PIF
      thermosensing pathway. Instead, elevated temperature promotes translocation of
      bacterial effector proteins into plant cells and causes a loss of ICS1-mediated
      salicylic acid (SA) biosynthesis. Global transcriptome analysis reveals a major
      temperature-sensitive node of SA signalling, impacting ~60% of benzothiadiazole
      (BTH)-regulated genes, including ICS1 and the canonical SA marker gene, PR1.
      Remarkably, BTH can effectively protect Arabidopsis against Pst DC3000 infection
      at elevated temperature despite the lack of ICS1 and PR1 expression. Our results
      highlight the broad impact of a major climate condition on the enigmatic
      molecular interplay between temperature, SA defence and function of a central
      bacterial virulence system in the context of a widely studied susceptible plant
      pathogen interaction.

PMID- 29180700
TI  - Autophagy protects pancreatic beta cell mass and function in the setting of a
      high-fat and high-glucose diet.
AB  - Autophagy is a major regulator of pancreatic beta cell homeostasis. Altered
      autophagic activity has been implicated in the beta cells of patients with type 2
      diabetes, and in the beta cells of obese diabetic rodents. Here, we show that
      autophagy was induced in beta cells by either a high-fat diet or a combined high
      fat and high-glucose diet, but not by high-glucose alone. However, a high-glucose
      intake alone did increase beta cell mass and insulin secretion moderately.
      Depletion of Atg7, a necessary component of the autophagy pathway, in beta cells
      by pancreatic intra-ductal AAV8-shAtg7 infusion in C57BL/6 mice, resulted in
      decreased beta cell mass, impaired glucose tolerance, defective insulin
      secretion, and increased apoptosis when a combined high-fat and high-glucose diet
      was given, seemingly due to suppression of autophagy. Taken together, our
      findings suggest that the autophagy pathway may act as a protective mechanism in
      pancreatic beta cells during a high-calorie diet.

PMID- 29180699
TI  - Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and
      persistence.
AB  - Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the
      development of gliomas and other human malignancies. Mutant IDH1 induces
      epigenetic changes that promote tumorigenesis, but the scale and reversibility of
      these changes are unknown. Here, using human astrocyte and glioma tumorsphere
      systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic
      reprogramming. We characterize the reversibility of the alterations in DNA
      methylation, the histone landscape, and transcriptional reprogramming that occur
      following IDH1 mutation. We discover genome-wide coordinate changes in the
      localization and intensity of multiple histone marks and chromatin states. Mutant
      IDH1 establishes a CD24+ population with a proliferative advantage and stem-like
      transcriptional features. Strikingly, prolonged exposure to mutant IDH1 results
      in irreversible genomic and epigenetic alterations. Together, these observations
      provide unprecedented high-resolution molecular portraits of mutant-IDH1
      dependent epigenomic reprogramming. These findings have substantial implications
      for understanding of mutant IDH function and for optimizing therapeutic
      approaches to targeting IDH-mutant tumors.

PMID- 29180701
TI  - Longitudinal study of visual field changes determined by Humphrey Field Analyzer
      10-2 in patients with Retinitis Pigmentosa.
AB  - The aim of this study is to determine the progress of the visual field defects
      obtained by the Humphrey Field Analyzer 10-2 program (HFA 10-2) in patients with
      retinitis pigmentosa (RP). The medical records of 45 eyes of 45 RP patients who
      had at least 3 visual field tests were reviewed. Linear mixed models were used to
      follow the changes of the mean deviation and the average sensitivity of 4, 12,
      and 20 points in three concentric squares, designated as S4, S12, and S20. The
      median follow-up time was 3.86 years [range: 1.93 to 9.86, IQR (Interquartile
      range): 3.01 to 4.93]. The median number of the visual field tests was 3 (range:
      3 to 15, IQR: 3 to 4). The mean change of the MD was -0.46 dB/year (-5.80%/year).
      When the patients were grouped by the average initial MD, the less advanced group
      had slower progressions than the more advanced group in S4, S12, and S20. These
      results should be useful in understanding the pathological changes of RP in the
      central visual field.

PMID- 29180702
TI  - Developing a Machine Learning System for Identification of Severe Hand, Foot, and
      Mouth Disease from Electronic Medical Record Data.
AB  - Children of severe hand, foot, and mouth disease (HFMD) often present with same
      clinical features as those of mild HFMD during the early stage, yet later
      deteriorate rapidly with a fulminant disease course. Our goal was to: (1) develop
      a machine learning system to automatically identify cases with high risk of
      severe HFMD at the time of admission; (2) compare the effectiveness of the new
      system with the existing risk scoring system. Data on 2,532 HFMD children
      admitted between March 2012 and July 2015, were collected retrospectively from a
      medical center in China. By applying a holdout strategy and a 10-fold cross
      validation method, we developed four models with the random forest algorithm
      using different variable sets. The prediction system HFMD-RF based on the model
      of 16 variables from both the structured and unstructured data, achieved 0.824
      sensitivity, 0.931 specificity, 0.916 accuracy, and 0.916 area under the curve in
      the independent test set. Most remarkably, HFMD-RF offers significant gains with
      respect to the commonly used pediatric critical illness score in clinical
      practice. As all the selected risk factors can be easily obtained, HFMD-RF might
      prove to be useful for reductions in mortality and complications of severe HFMD.

PMID- 29180703
TI  - Comparison of graphical optimization or IPSA for improving brachytheraphy plans
      associated with inadequate target coverage for cervical cancer.
AB  - Many studies have reported that inverse planning by simulated annealing (IPSA)
      can improve the quality of brachytherapy plans, and we wanted to examine whether
      IPSA could improve cervical cancer brachytherapy plans giving D90 < 6 Gy (with 7
      Gy per fraction) at our institution. Various IPSA plans involving the tandem and
      ovoid applicators were developed for 30 consecutive cervical cancer patients on
      the basis of computed tomography: IPSA1, with a constraint on the maximum dose in
      the target volume; IPSA1-0, identical to IPSA1 but without a dwell-time deviation
      constraint; IPSA2, without a constraint on the maximum dose; and IPSA2-0,
      identical to IPSA2 but without a dwell-time deviation constraint. IPSA2 achieved
      similar results as graphical optimization, and none of the other IPSA plans was
      significantly better than graphical optimization. Therefore, other approaches,
      such as combining interstitial and intracavitary brachytherapy, may be more
      appropriate for improving the quality of brachytherapy plans associated with
      inadequate target coverage.

PMID- 29180705
TI  - Rapid morphological change of a top predator with the invasion of a novel prey.
AB  - Invasive exotic species are spreading rapidly throughout the planet. These
      species can have widespread impacts on biodiversity, yet the ability for native
      species, particularly long-lived vertebrates, to respond rapidly to invasions
      remains mostly unknown. Here we provide evidence of rapid morphological change in
      the endangered snail kite (Rostrhamus sociabilis) across its North American range
      with the invasion of a novel prey, the island apple snail (Pomacea maculata), a
      much larger congener of the kite's native prey. In less than one decade since
      invasion, snail kite bill size and body mass increased substantially. Larger
      bills should be better suited to extracting meat from the larger snail shells,
      and we detected strong selection on increased size through juvenile survival.
      Using pedigree data, we found evidence of both genetic and environmental
      influences on trait expression and discovered that additive genetic variation in
      bill size increased with invasion. However, trends in predicted breeding values
      emphasize that recent morphological changes have been driven primarily by
      phenotypic plasticity rather than micro-evolutionary change. Our findings suggest
      that evolutionary change may be imminent and underscore that even long-lived
      vertebrates can respond quickly to invasive species. Furthermore, these results
      highlight that phenotypic plasticity may provide a crucial role for predators
      experiencing rapid environmental change.

PMID- 29180704
TI  - Vps34 PI 3-kinase inactivation enhances insulin sensitivity through reprogramming
      of mitochondrial metabolism.
AB  - Vps34 PI3K is thought to be the main producer of phosphatidylinositol-3
      monophosphate, a lipid that controls intracellular vesicular trafficking. The
      organismal impact of systemic inhibition of Vps34 kinase activity is not
      completely understood. Here we show that heterozygous Vps34 kinase-dead mice are
      healthy and display a robustly enhanced insulin sensitivity and glucose
      tolerance, phenotypes mimicked by a selective Vps34 inhibitor in wild-type mice.
      The underlying mechanism of insulin sensitization is multifactorial and not
      through the canonical insulin/Akt pathway. Vps34 inhibition alters cellular
      energy metabolism, activating the AMPK pathway in liver and muscle. In liver,
      Vps34 inactivation mildly dampens autophagy, limiting substrate availability for
      mitochondrial respiration and reducing gluconeogenesis. In muscle, Vps34
      inactivation triggers a metabolic switch from oxidative phosphorylation towards
      glycolysis and enhanced glucose uptake. Our study identifies Vps34 as a new drug
      target for insulin resistance in Type-2 diabetes, in which the unmet therapeutic
      need remains substantial.

PMID- 29180707
TI  - Flow regime alteration degrades ecological networks in riparian ecosystems.
AB  - Riverine ecosystems are governed by patterns of temporal variation in river
      flows. This dynamism will change due to climate change and the near-ubiquitous
      human control of river flows globally, which may have severe effects on species
      distributions and interactions. We employed a combination of population modelling
      and network theory to explore the consequences of possible flow regime futures on
      riparian plant communities, including scenarios of increased drought, flooding
      and flow homogenization (removal of flow variability). We found that even slight
      modifications to the historic natural flow regime had significant consequences
      for the structure of riparian plant networks. Networks of emergent interactions
      between plant guilds were most connected at the natural flow regime and became
      simplified with increasing flow alteration. The most influential component of
      flow alteration was flood reduction, with drought and flow homogenization both
      having greater simplifying community-wide consequences than increased flooding.
      These findings suggest that maintaining floods under future climates will be
      needed to overcome the negative long-term consequences of flow modification on
      riverine ecosystems.

PMID- 29180708
TI  - Outstanding research opportunities at the interface of evolution and medicine.

PMID- 29180709
TI  - Predation drives local adaptation of phenotypic plasticity.
AB  - Phenotypic plasticity is the ability of an individual genotype to alter aspects
      of its phenotype depending on the current environment. It is central to the
      persistence, resistance and resilience of populations facing variation in
      physical or biological factors. Genetic variation in plasticity is pervasive,
      which suggests its local adaptation is plausible. Existing studies on the
      adaptation of plasticity typically focus on single traits and a few populations,
      while theory about interactions among genes (for example, pleiotropy) suggests
      that a multi-trait, landscape scale (for example, multiple populations)
      perspective is required. We present data from a landscape scale, replicated,
      multi-trait experiment using a classic predator-prey system centred on the water
      flea Daphnia pulex. We find predator regime-driven differences in genetic
      variation of multivariate plasticity. These differences are associated with
      strong divergent selection linked to a predation regime. Our findings are
      evidence for local adaptation of plasticity, suggesting that responses of
      populations to environmental variation depend on the conditions in which they
      evolved in the past.

PMID- 29180706
TI  - Complexity and conservation of regulatory landscapes underlie evolutionary
      resilience of mammalian gene expression.
AB  - To gain insight into how mammalian gene expression is controlled by rapidly
      evolving regulatory elements, we jointly analysed promoter and enhancer activity
      with downstream transcription levels in liver samples from 15 species. Genes
      associated with complex regulatory landscapes generally exhibit high expression
      levels that remain evolutionarily stable. While the number of regulatory elements
      is the key driver of transcriptional output and resilience, regulatory
      conservation matters: elements active across mammals most effectively stabilize
      gene expression. In contrast, recently evolved enhancers typically contribute
      weakly, consistent with their high evolutionary plasticity. These effects are
      observed across the entire mammalian clade and are robust to potential
      confounders, such as the gene expression level. Using liver as a representative
      somatic tissue, our results illuminate how the evolutionary stability of gene
      expression is profoundly entwined with both the number and conservation of
      surrounding promoters and enhancers.

PMID- 29180710
TI  - Biodiversity-multifunctionality relationships depend on identity and number of
      measured functions.
AB  - Biodiversity ensures ecosystem functioning and provisioning of ecosystem
      services, but it remains unclear how biodiversity-ecosystem multifunctionality
      relationships depend on the identity and number of functions considered. Here, we
      demonstrate that ecosystem multifunctionality, based on 82 indicator variables of
      ecosystem functions in a grassland biodiversity experiment, increases strongly
      with increasing biodiversity. Analysing subsets of functions showed that the
      effects of biodiversity on multifunctionality were stronger when more functions
      were included and that the strength of the biodiversity effects depended on the
      identity of the functions included. Limits to multifunctionality arose from
      negative correlations among functions and functions that were not correlated with
      biodiversity. Our findings underline that the management of ecosystems for the
      protection of biodiversity cannot be replaced by managing for particular
      ecosystem functions or services and emphasize the need for specific management to
      protect biodiversity. More plant species from the experimental pool of 60 species
      contributed to functioning when more functions were considered. An individual
      contribution to multifunctionality could be demonstrated for only a fraction of
      the species.

PMID- 29180711
TI  - Global patterns in marine predatory fish.
AB  - Large teleost (bony) fish are a dominant group of predators in the oceans and
      constitute a major source of food and livelihood for humans. These species differ
      markedly in morphology and feeding habits across oceanic regions; large pelagic
      species such as tunas and billfish typically occur in the tropics, whereas
      demersal species of gadoids and flatfish dominate boreal and temperate regions.
      Despite their importance for fisheries and the structuring of marine ecosystems,
      the underlying factors determining the global distribution and productivity of
      these two groups of teleost predators are poorly known. Here, we show how
      latitudinal differences in predatory fish can essentially be explained by the
      inflow of energy at the base of the pelagic and benthic food chain. A low
      productive benthic energy pathway favours large pelagic species, whereas equal
      productivities support large demersal generalists that outcompete the pelagic
      specialists. Our findings demonstrate the vulnerability of large teleost
      predators to ecosystem-wide changes in energy flows and hence provide key insight
      to predict the responses of these important marine resources under global change.

PMID- 29180712
TI  - Colour discrimination thresholds in type 1 Bipolar Disorder: a pilot study.
AB  - Although some studies have reported perceptual changes in psychosis, no
      definitive conclusions have been drawn about visual disturbances that are related
      to bipolar disorder (BPD). The purpose of the present study was to evaluate
      colour vision in BPD patients. Data were recorded from 24 participants: healthy
      control group (n = 12) and type 1 BPD group (n = 12). The participants were 20-45
      years old and they were free from neurological disorders and identifiable ocular
      disease and had normal or corrected-to-normal visual acuity. Colour
      discrimination was evaluated using the Lanthony D-15d, Trivector and Ellipse
      tests, using a psychophysical forced-choice method. The relationship of visual
      measures to mood state and cognitive function was also investigated. The results
      showed that BPD patients had higher colour discrimination thresholds in the D15d
      (p < 0.001), Trivector (p < 0.001) and Ellipse (p < 0.01) tests compared with
      healthy controls. Linear regression analysis showed that mood state was related
      to colour discrimination. BPD individuals were not impaired in cognitive tasks.
      The present study provided new evidence of potential links between type 1 BPD and
      visual processing impairments. This research suggests a new direction for studies
      and the need for research in this field of study.

PMID- 29180713
TI  - Metabolic regulatory oscillations in intertidal green seaweed Ulva lactuca
      against tidal cycles.
AB  - The survival of wetland plant species largely relies on physiological adaptations
      essential for submergence and desiccation. Intertidal seaweeds, unlike
      terrestrial plants, have unique adaptations to submergence and can also sustain
      desiccation arising from tidal rhythms. This study determined the differential
      metabolic regulations in the inter-tidal seaweed species Ulva lactuca against the
      submergence and desiccation. During desiccation, the relative water content of
      the algal thalli declined with concomitant increase in reactive oxygen species
      (ROS) and lipid peroxidation. Nevertheless, the trends reversed during recovery
      on re-submergence and attained homeostasis. Metabolite profiling of U. lactuca
      revealed desiccation induced balance in energy reserve utilization by adjusting
      carbohydrate metabolism and switch over to ammonia metabolism. Upon re
      submergence, thalli showed an increase in fermentative metabolites, pyruvate
      alanine conversion, and the GABA shunt. Prolonged submergence induced substrate
      level phosphorylation mediated sugar biosynthesis while continuing the
      alternative carbon flux through fermentative metabolism, an increase in
      osmoprotectants glycine and betaine, sulfur bearing compounds cysteine and
      hypotaurine, and phenolic compound coniferaldehyde. The determined metabolic
      regulations in U. lactuca for submergence tolerance provide insights into
      potential evolutionarily conserved protective mechanisms across the green lineage
      and also highlights the possible role of sulfur oxoforms as strong free radical
      scavengers.

PMID- 29180714
TI  - Unraveling the molecular mechanism of photosynthetic toxicity of highly
      fluorescent silver nanoclusters to Scenedesmus obliquus.
AB  - While the discovery of numerous attractive properties of silver at the nanoscale
      has increased their demand in many sectors including medicine, optics, sensing,
      painting and cosmetics, it has also raised wide public concerns about their
      effect on living organisms in aquatic environment. Despite the continuous effort
      to understand the various aspects of the toxicity of silver nanomaterials, the
      molecular level understanding on their cytotoxicity mechanism to biological
      organisms has remained unclear. Herein, we demonstrated the underlying mechanism
      of the photosynthetic toxicity against green algae namely, Scenedesmus obliquus
      by using an emerging silver nanomaterial, called silver nanoclusters (defined as
      r-Ag NCs). By exploiting the unique fluorescence properties of r-Ag NCs along
      with various other analytical/biological tools, we proposed that the
      photosynthetic toxicity of r-Ag NCs was largely attributed to the "joint
      toxicity" effect of particulate form of r-Ag NCs and its released Ag+, which
      resulted in the disruption of the electron transport chain of light reaction and
      affected the content of key enzymes (RuBP carboxylase/ oxygenase) of Calvin cycle
      of algae cells. We believe that the present study can also be applied to the
      assessment of the ecological risk derived from other metal nanoparticles.

PMID- 29180715
TI  - A PLGA-reinforced PEG in situ gel formulation for improved sustainability of
      hypoglycaemic activity of glimepiride in streptozotocin-induced diabetic rats.
AB  - Glimepiride (GMD) is a third-generation sulfonylurea derivative and one of the
      top three most-prescribed oral antidiabetic drugs. The need for a depot
      formulation exists, and a safe and effective antidiabetic therapy is the goal of
      this study. The aims were to design a depot in situ gel (ISG) formulation and
      investigate the main factors that control the initial burst and sustain the GMD
      effect using the Box-Behnken design. The studied factors were polymer percent
      (X1), plasticizer percent (X2) and benzyl benzoate percent in N-methyl-2
      pyrrolidone (X3). The results revealed that X2 is the only factor that showed
      significant effects on all investigated responses. Scanning electron microscopy
      images showed that an increase in PEG % improved the smoothness and reduced the
      porosity of the ISG formulation surface. The GMD plasma levels in diabetic rats
      revealed no significant difference (p < 0.05) between the maximum GMD plasma
      concentrations of the optimized GMD-ISG formula (10 mg/ kg) and oral marketed GMD
      tablets (1 mg/kg). This result ensures that the optimized formula does not exceed
      the maximum safe plasma concentration. In addition, the optimized GMD-ISG
      formulation showed a depot effect that lasted for 14 days post-injection. This
      approach to controlling GMD release using an in situ forming system could be
      useful for improving patient compliance and diabetes treatment effectiveness.

PMID- 29180716
TI  - Drosophila Kruppel homolog 1 represses lipolysis through interaction with dFOXO.
AB  - Transcriptional coordination is a vital process contributing to metabolic
      homeostasis. As one of the key nodes in the metabolic network, the forkhead
      transcription factor FOXO has been shown to interact with diverse transcription
      co-factors and integrate signals from multiple pathways to control metabolism,
      oxidative stress response, and cell cycle. Recently, insulin/FOXO signaling has
      been implicated in the regulation of insect development via the interaction with
      insect hormones, such as ecdysone and juvenile hormone. In this study, we
      identified an interaction between Drosophila FOXO (dFOXO) and the zinc finger
      transcription factor Kruppel homolog 1 (Kr-h1), one of the key players in
      juvenile hormone signaling. We found that Kr-h1 mutants show delayed larval
      development and altered lipid metabolism, in particular induced lipolysis upon
      starvation. Notably, Kr-h1 physically and genetically interacts with dFOXO in
      vitro and in vivo to regulate the transcriptional activation of insulin receptor
      (InR) and adipose lipase brummer (bmm). The transcriptional co-regulation by Kr
      h1 and dFOXO may represent a broad mechanism by which Kruppel-like factors
      integrate with insulin signaling to maintain metabolic homeostasis and coordinate
      organism growth.

PMID- 29180717
TI  - Three-year monitoring of genetic diversity reveals a micro-connectivity pattern
      and local recruitment in the broadcast marine species Paracentrotus lividus.
AB  - In conservation and management of marine biological resources, a knowledge of
      connectivity is necessary to understand how local populations are naturally
      replenished by the arrival of new recruits from source populations. At small
      geographical scales, species experiencing moderate to long pelagic larval phases
      are mostly genetically homogeneous, which hinders inferences about local
      connectivity. Recent studies demonstrated that assessing genetic relatedness and
      kinship could provide information about local connectivity in populations with
      high levels of gene flow. Here, we were interested in deciphering the structure
      and connectivity of populations of the sea urchin Paracentrotus lividus, by
      monitoring populations at 11 localities distributed along a 225-km coast-line in
      the south-eastern French Mediterranean Sea. Using 12 microsatellite loci, we
      found a weak but significant genetic differentiation and observed a transient
      genetic differentiation among locations within temporal cohorts, without any
      correlation with the distance between locations, interpreted as unexplainable
      chaotic genetic patchiness. Among temporal cohorts, the more related individuals
      were mainly found within locations and the observed local differentiation (FST)
      correlated with the proportion of kin within locations, suggesting that larvae
      dispersed cohesively. Specifically, we could also reveal that populations
      flanking Cape Sicie were influenced by eastern populations and that local
      recruitment was a frequent occurrence. Overall, our results contribute to the
      growing number of studies showing that connectivity can be reliably assessed at a
      fine spatial scale even in genetically homogenous populations.

PMID- 29180718
TI  - Efficiency of genomic prediction of non-assessed single crosses.
AB  - An important application of genomic selection in plant breeding is predicting
      untested single crosses (SCs). Most investigations on the prediction efficiency
      were based on tested SCs using cross-validation. The main objective was to assess
      the prediction efficiency by correlating the predicted and true genotypic values
      of untested SCs (accuracy) and measuring the efficacy of identification of the
      best 300 untested SCs (coincidence) using simulated data. We assumed 10,000 SNPs,
      400 QTLs, two groups of 70 selected DH lines, and 4900 SCs. The heritabilities
      for the assessed SCs were 30, 60, and 100%. The scenarios included three sampling
      processes of DH lines, two sampling processes of SCs for testing, two SNP
      densities, DH lines from distinct and the same populations, DH lines from
      populations with lower LD, two genetic models, three statistical models, and
      three statistical approaches. We derived a model for genomic prediction based on
      SNP average effects of substitution and dominance deviations. The prediction
      accuracy is not affected by the linkage phase. The prediction of untested SCs is
      very efficient. The accuracies and coincidences ranged from ~0.8 and 0.5 at low
      heritability to 0.9 and 0.7 at high heritability, respectively. We also highlight
      the relevance of the overall LD and demonstrate that efficient prediction of
      untested SCs can be achieved for crops that show no heterotic pattern, for
      reduced training set size (10%), for SNP density of 1 cM, and for distinct
      sampling processes of DH lines based on random choice of the SCs for testing.

PMID- 29180719
TI  - Population mitogenomics provides insights into evolutionary history, source of
      invasions and diversifying selection in the House Crow (Corvus splendens).
AB  - The House Crow (Corvus splendens) is a useful study system for investigating the
      genetic basis of adaptations underpinning successful range expansion. The species
      originates from the Indian subcontinent, but has successfully spread through a
      variety of thermal environments across Asia, Africa and Europe. Here, population
      mitogenomics was used to investigate the colonisation history and to test for
      signals of molecular selection on the mitochondrial genome. We sequenced the
      mitogenomes of 89 House Crows spanning four native and five invasive populations.
      A Bayesian dated phylogeny, based on the 13 mitochondrial protein-coding genes,
      supports a mid-Pleistocene (~630,000 years ago) divergence between the most
      distant genetic lineages. Phylogeographic patterns suggest that northern South
      Asia is the likely centre of origin for the species. Codon-based analyses of
      selection and assessments of changes in amino acid properties provide evidence of
      positive selection on the ND2 and ND5 genes against a background of purifying
      selection across the mitogenome. Protein homology modelling suggests that four
      amino acid substitutions inferred to be under positive selection may modulate
      coupling efficiency and proton translocation mediated by OXPHOS complex I. The
      identified substitutions are found within native House Crow lineages and
      ecological niche modelling predicts suitable climatic areas for the establishment
      of crow populations within the invasive range. Mitogenomic patterns in the
      invasive range of the species are more strongly associated with introduction
      history than climate. We speculate that invasions of the House Crow have been
      facilitated by standing genetic variation that accumulated due to diversifying
      selection within the native range.

PMID- 29180720
TI  - SNX27 links DGKzeta to the control of transcriptional and metabolic programs in T
      lymphocytes.
AB  - Sorting nexin 27 (SNX27) recycles PSD-95, Dlg1, ZO-1 (PDZ) domain-interacting
      membrane proteins and is essential to sustain adequate brain functions. Here we
      define a fundamental SNX27 function in T lymphocytes controlling antigen-induced
      transcriptional activation and metabolic reprogramming. SNX27 limits the
      activation of diacylglycerol (DAG)-based signals through its high affinity PDZ
      interacting cargo DAG kinase zeta (DGKzeta). SNX27 silencing in human T cells
      enhanced T cell receptor (TCR)-stimulated activator protein 1 (AP-1)- and nuclear
      factor kappaB (NF-kappaB)-mediated transcription. Transcription did not increase
      upon DGKzeta silencing, suggesting that DGKzeta function is dependent on SNX27.
      The enhanced transcriptional activation in SNX27-silenced cells contrasted with
      defective activation of the mammalian target of rapamycin (mTOR) pathway. The
      analysis of Snx27 -/- mice supported a role for SNX27 in the control of T cell
      growth. This study broadens our understanding of SNX27 as an integrator of lipid
      based signals with the control of transcription and metabolic pathways.

PMID- 29180721
TI  - 5D proteomic approach for the biomarker search in plasma: Acute myeloid leukaemia
      as a case study.
AB  - Acute myeloid leukaemia (AML) is a type of cancer affecting all ages but it is
      more common in adults, as compared to children. Recent advancements in proteomics
      and mass spectrometry tools, offer a comprehensive solution to study the
      molecular complexity of diseases, such as cancers. This study is focused on the
      proteomic profiling of AML in comparison to healthy control for which, a
      systematic 5D proteomic approach for the fractionation of pooled plasma samples
      was used. Methodology includes depletion of Top-7 abundant proteins, ZOOM
      isoelectric focusing (ZOOM-IEF), two-dimensional gel electrophoresis (2-DGE), and
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis
      followed by the validation of identified biomarker proteins using enzyme linked
      immunosorbent assay (ELISA). Up-/down-fold changes in concentration of proteins
      were observed in 2-DGE of AML in comparison with the healthy control and a total
      of 34 proteins were identified in fractioned plasma. Among them, fifteen proteins
      were significantly differentiated and five proteins; SAA1, complement factor C7,
      ApoE, plasminogen, and ApoA1 were later verified by ELISA in individual samples,
      which showed that SAA1 and plasminogen could be used as potential biomarker for
      AML.

PMID- 29180722
TI  - Rare non-coding variants are associated with plasma lipid traits in a founder
      population.
AB  - Founder populations are ideally suited for studies on the clinical effects of
      alleles that are rare in general populations but occur at higher frequencies in
      these isolated populations. Whole genome sequencing in 98 Hutterites, a founder
      population of European descent, and subsequent imputation revealed 660,238 single
      nucleotide polymorphisms that are rare (<1%) or absent in European populations,
      but occur at frequencies >1% in the Hutterites. We examined the effects of these
      rare in European variants on plasma lipid levels in 828 Hutterites and applied a
      Bayesian hierarchical framework to prioritize potentially causal variants based
      on functional annotations. We identified two novel non-coding rare variants
      associated with LDL cholesterol (rs17242388 in LDLR) and HDL cholesterol
      (rs189679427 between GOT2 and APOOP5), and replicated previous associations of a
      splice variant in APOC3 (rs138326449) with triglycerides and HDL-C. All three
      variants are at well-replicated loci in GWAS but are independent from and have
      larger effect sizes than the known common variation in these regions. Candidate
      eQTL analyses in in LCLs in the Hutterites suggest that these rare non-coding
      variants are likely to mediate their effects on lipid traits by regulating gene
      expression.

PMID- 29180723
TI  - Neuromodulation of orexin neurons reduces diet-induced adiposity.
AB  - BACKGROUND/OBJECTIVES: Low levels of orexin are associated with obesity and
      reduced physical activity in humans and animals. SUBJECTS/METHODS: Designer
      Receptors Exclusively Activated by Designer Drugs (DREADDs) selectively activated
      orexin neurons in mouse lateral hypothalamus (LH) to measure effects on
      spontaneous physical activity (SPA). DREADD targeting was achieved by stereotaxic
      injection of AAV vectors into caudal lateral LH of heterozygous orexin-Cre or
      C57/B6J mice. In one set of studies, excitation of orexin neurons was examined
      (virus: AAV2-EF1a-DIO-hM3Dq-mCherry), and test sessions began 3-4 h after light
      cycle onset. In a study examining the inhibition of orexin neurons (virus: AAV2
      hSyn-DIO-hM4Di-mCherry), testing began 15 min prior to dark cycle onset.
      Clozapine n-oxide (CNO; 1 or 5 mg/kg) or saline was injected intraperitoneally
      and time spent moving in open field chambers was recorded for 2 h. Follow-up
      studies in separate mouse cohorts quantified SPA in parallel with changes in
      energy expenditure (EE) and chow intake using indirect calorimetry chambers
      (SableSystemTM). Following acclimation, testing sessions (saline and/or CNO) took
      place over the course of ~1 week, with injections administered every day. Changes
      in SPA, EE, chow intake, fecal boli, and body composition (EchoMRITM) were
      measured. Additional mice cohorts were fed a high-fat diet (HFD) and injected
      with CNO daily up to 10 days to assess the potential for orexin activation to
      prevent diet-induced obesity. RESULTS: Activation of orexin resulted in increases
      in SPA in male and female mice, and was accompanied by increases in energy
      expenditure without changes in overall chow intake. When orexin activation
      occurred in the context of high fat diet, weight gain and adiposity were
      significantly attenuated. SPA was decreased when DREADDs were used to inhibit
      orexin activity. CONCLUSION: These results demonstrate that orexin neurons play a
      critical role in mediating physical activity and suggest a novel therapeutic
      target for treating obesity.

PMID- 29180724
TI  - Novel Common Variants Associated with Obesity and Type 2 Diabetes Detected Using
      a cFDR Method.
AB  - Genome-wide association studies (GWASs) have been performed extensively in
      diverse populations to identify single nucleotide polymorphisms (SNPs) associated
      with complex diseases or traits. However, to date, the SNPs identified fail to
      explain a large proportion of the variance of the traits/diseases. GWASs on type
      2 diabetes (T2D) and obesity are generally focused on individual traits
      independently, and genetic intercommunity (common genetic contributions or the
      product of over correlated phenotypic world) between them are largely unknown,
      despite extensive data showing that these two phenotypes share both genetic and
      environmental risk factors. Here, we applied a recently developed genetic
      pleiotropic conditional false discovery rate (cFDR) approach to discover novel
      loci associated with BMI and T2D by incorporating the summary statistics from
      existing GWASs of these two traits. Conditional Q-Q and fold enrichment plots
      were used to visually demonstrate the strength of pleiotropic enrichment.
      Adopting a cFDR nominal significance level of 0.05, 287 loci were identified for
      BMI and 75 loci for T2D, 23 of which for both traits. By incorporating related
      traits into a conditional analysis framework, we observed significant pleiotropic
      enrichment between obesity and T2D. These findings may provide novel insights
      into the etiology of obesity and T2D, individually and jointly.

PMID- 29180727
TI  - Cancer immunotherapy: Rewiring cancer cells.

PMID- 29180728
TI  - Cryo-electron microscopy makes waves in pharma labs.

PMID- 29180725
TI  - Activation of Vibrio cholerae quorum sensing promotes survival of an arthropod
      host.
AB  - Vibrio cholerae colonizes the human terminal ileum to cause cholera, and the
      arthropod intestine and exoskeleton to persist in the aquatic environment.
      Attachment to these surfaces is regulated by the bacterial quorum-sensing signal
      transduction cascade, which allows bacteria to assess the density of microbial
      neighbours. Intestinal colonization with V. cholerae results in expenditure of
      host lipid stores in the model arthropod Drosophila melanogaster. Here we report
      that activation of quorum sensing in the Drosophila intestine retards this
      process by repressing V. cholerae succinate uptake. Increased host access to
      intestinal succinate mitigates infection-induced lipid wasting to extend survival
      of V. cholerae-infected flies. Therefore, quorum sensing promotes a more
      favourable interaction between V. cholerae and an arthropod host by reducing the
      nutritional burden of intestinal colonization.

PMID- 29180726
TI  - Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in
      susceptible mice.
AB  - Antibiotic exposure in children has been associated with the risk of inflammatory
      bowel disease (IBD). Antibiotic use in children or in their pregnant mother can
      affect how the intestinal microbiome develops, so we asked whether the transfer
      of an antibiotic-perturbed microbiota from mothers to their children could affect
      their risk of developing IBD. Here we demonstrate that germ-free adult pregnant
      mice inoculated with a gut microbial community shaped by antibiotic exposure
      transmitted their perturbed microbiota to their offspring with high fidelity.
      Without any direct or continued exposure to antibiotics, this dysbiotic
      microbiota in the offspring remained distinct from controls for at least 21
      weeks. By using both IL-10-deficient and wild-type mothers, we showed that both
      inoculum and genotype shape microbiota populations in the offspring. Because IL10
      /- mice are genetically susceptible to colitis, we could assess the risk due to
      maternal transmission of an antibiotic-perturbed microbiota. We found that the
      IL10-/- offspring that had received the perturbed gut microbiota developed
      markedly increased colitis. Taken together, our findings indicate that antibiotic
      exposure shaping the maternal gut microbiota has effects that extend to the
      offspring, with both ecological and long-term disease consequences.

PMID- 29180729
TI  - Infectious disease: Fighting influenza B.

PMID- 29180731
TI  - Obesity: GDF15 tells the brain to lose weight.

PMID- 29180732
TI  - Small molecules against RNA targets attract big backers.

PMID- 29180730
TI  - GPCRs: Crystal structure of D4 dopamine receptor.

PMID- 29180734
TI  - BTK inhibitors get a boost.

PMID- 29180733
TI  - Second anticancer CAR T therapy receives FDA approval.

PMID- 29180735
TI  - Diabetes: Selective FOXO1 modulation.

PMID- 29180736
TI  - FDA approves first digital pill.

PMID- 29180737
TI  - Polypharmacology: Repurposing ceritinib.

PMID- 29180738
TI  - Mantle hydration and the role of water in the generation of large igneous
      provinces.
AB  - The genesis of large igneous provinces (LIP) is controlled by multiple factors
      including anomalous mantle temperatures, the presence of fusible fertile
      components and volatiles in the mantle source, and the extent of decompression.
      The lack of a comprehensive examination of all these factors in one specific LIP
      makes the mantle plume model debatable. Here, we report estimates of the water
      content in picrites from the Emeishan LIP in southwestern China. Although these
      picrites display an island arc-like H2O content (up to 3.4 by weight percent),
      the trace element characteristics do not support a subduction zone setting but
      point to a hydrous reservoir in the deep mantle. Combining with previous studies,
      we propose that hydrous and hot plumes occasionally appeared in the Phanerozoic
      era to produce continental LIPs (e.g., Tarim, Siberian Trap, Karoo). The wide
      sampling of hydrous reservoirs in the deep mantle by mantle plumes thus indicates
      that the Earth's interior is largely hydrated.

PMID- 29180739
TI  - Transport and Association of Ions in Lithium Battery Electrolytes Based on Glycol
      Ether Mixed with Halogen-Free Orthoborate Ionic Liquid.
AB  - Ion transport behaviour of halogen-free hybrid electrolytes for lithium-ion
      batteries based on phosphonium bis(salicylato)borate [P4,4,4,8][BScB] ionic
      liquid mixed with diethylene glycol dibutyl ether (DEGDBE) is investigated. The
      Li[BScB] salt is dissolved at different concentrations in the range from 0.15 mol
      kg-1 to 1.0 mol kg-1 in a mixture of [P4,4,4,8][BScB] and DEGDBE in 1:5 molar
      ratio. The ion transport properties of the resulting electrolytes are
      investigated using viscosity, electrical impedance spectroscopy and pulsed-Field
      Gradient (PFG) NMR. The apparent transfer numbers of ions are calculated from the
      diffusion coefficients measured by using PFG NMR. PFG NMR data suggested ion
      association upon addition of Li salt to the [P4,4,4,8][BScB] in DEGDBE solution.
      This is further confirmed by liquid state 7Li and 11B NMR, and FTIR spectroscopic
      techniques, which suggest strong interactions between the lithium cation and
      oxygen atoms of the [BScB]- anion in the hybrid electrolytes.

PMID- 29180740
TI  - High-efficiency exfoliation of large-area mono-layer graphene oxide with
      controlled dimension.
AB  - In this work, we introduce a novel and facile method of exfoliating large-area,
      single-layer graphene oxide using a shearing stress. The shearing stress reactor
      consists of two concentric cylinders, where the inner cylinder rotates at
      controlled speed while the outer cylinder is kept stationary. We found that the
      formation of Taylor vortex flow with shearing stress can effectively exfoliate
      the graphite oxide, resulting in large-area single- or few-layer graphene oxide
      (GO) platelets with high yields (>90%) within 60 min of reaction time. Moreover,
      the lateral size of exfoliated GO sheets was readily tunable by simply
      controlling the rotational speed of the reactor and reaction time. Our approach
      for high-efficiency exfoliation of GO with controlled dimension may find its
      utility in numerous industrial applications including energy storage, conducting
      composite, electronic device, and supporting frameworks of catalyst.

PMID- 29180741
TI  - Observation of Dirac bands in artificial graphene in small-period nanopatterned
      GaAs quantum wells.
AB  - Charge carriers in graphene behave like massless Dirac fermions (MDFs) with
      linear energy-momentum dispersion 1, 2 , providing a condensed-matter platform
      for studying quasiparticles with relativistic-like features. Artificial graphene
      (AG)-a structure with an artificial honeycomb lattice-exhibits novel phenomena
      due to the tunable interplay between topology and quasiparticle interactions 3-6
      . So far, the emergence of a Dirac band structure supporting MDFs has been
      observed in AG using molecular 5 , atomic 6, 7 and photonic systems 8-10 ,
      including those with semiconductor microcavities 11 . Here, we report the
      realization of an AG that has a band structure with vanishing density of states
      consistent with the presence of MDFs. This observation is enabled by a very small
      lattice constant (a = 50 nm) of the nanofabricated AG patterns superimposed on a
      two-dimensional electron gas hosted by a high-quality GaAs quantum well. Resonant
      inelastic light-scattering spectra reveal low-lying transitions that are not
      present in the unpatterned GaAs quantum well. These excitations reveal the energy
      dependence of the joint density of states for AG band transitions. Fermi level
      tuning through the Dirac point results in a collapse of the density of states at
      low transition energy, suggesting the emergence of the MDF linear dispersion in
      the AG.

PMID- 29180742
TI  - Out-of-plane heat transfer in van der Waals stacks through electron-hyperbolic
      phonon coupling.
AB  - Van der Waals heterostructures have emerged as promising building blocks that
      offer access to new physics, novel device functionalities and superior electrical
      and optoelectronic properties 1-7 . Applications such as thermal management,
      photodetection, light emission, data communication, high-speed electronics and
      light harvesting 8-16 require a thorough understanding of (nanoscale) heat flow.
      Here, using time-resolved photocurrent measurements, we identify an efficient out
      of-plane energy transfer channel, where charge carriers in graphene couple to
      hyperbolic phonon polaritons 17-19 in the encapsulating layered material. This
      hyperbolic cooling is particularly efficient, giving picosecond cooling times for
      hexagonal BN, where the high-momentum hyperbolic phonon polaritons enable
      efficient near-field energy transfer. We study this heat transfer mechanism using
      distinct control knobs to vary carrier density and lattice temperature, and find
      excellent agreement with theory without any adjustable parameters. These insights
      may lead to the ability to control heat flow in van der Waals heterostructures.

PMID- 29180743
TI  - A graphene Zener-Klein transistor cooled by a hyperbolic substrate.
AB  - The engineering of cooling mechanisms is a bottleneck in nanoelectronics. Thermal
      exchanges in diffusive graphene are mostly driven by defect-assisted acoustic
      phonon scattering, but the case of high-mobility graphene on hexagonal boron
      nitride (hBN) is radically different, with a prominent contribution of remote
      phonons from the substrate. Bilayer graphene on a hBN transistor with a local
      gate is driven in a regime where almost perfect current saturation is achieved by
      compensation of the decrease in the carrier density and Zener-Klein tunnelling
      (ZKT) at high bias. Using noise thermometry, we show that the ZKT triggers a new
      cooling pathway due to the emission of hyperbolic phonon polaritons in hBN by out
      of-equilibrium electron-hole pairs beyond the super-Planckian regime. The
      combination of ZKT transport and hyperbolic phonon polariton cooling renders
      graphene on BN transistors a valuable nanotechnology for power devices and RF
      electronics.

PMID- 29180745
TI  - Molecular variation of tomato yellow leaf curl virus in the insect vector Bemisia
      tabaci.
AB  - Insect vectors play significant roles in geminivirus spread and evolution in
      nature. To date little is known about the population dynamics of begomoviruses in
      their insect vector Bemisia tabaci. In this study we analyzed the genetic
      variation of tomato yellow leaf curl virus (TYLCV) in its host plant, Solanum
      lycopersicum, in its transmission vector B. tabaci raised on TYLCV-infected S.
      lycopersicum plants, and in B. tabaci after being transferred from S.
      lycopersicum to Gossypium hirsutum. We found that the levels of variability of
      TYLCV remained stable in S. lycopersicum plants, but increased significantly in
      both invasive and indigenous species of B. tabaci. We also presented evidence
      that the elevated mutation frequencies in TYLCV populations from vector
      whiteflies were caused mainly by mutations that occurred at several distinct
      sites within the TYLCV genome. Simultaneous introduction of mutations in the hot
      spots did not affect the ability of TYLCV to be transmitted by B. tabaci, but
      reduced its pathogenicity in both S. lycopersicum and Nicotiana benthamiana. Our
      findings provide new information on population variability of TYLCV in its insect
      vector, extending the knowledge of the influence of insect vector on plant virus
      population dynamics.

PMID- 29180744
TI  - Stem cell senescence drives age-attenuated induction of pituitary tumours in
      mouse models of paediatric craniopharyngioma.
AB  - Senescent cells may promote tumour progression through the activation of a
      senescence-associated secretory phenotype (SASP), whether these cells are capable
      of initiating tumourigenesis in vivo is not known. Expression of oncogenic beta
      catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters
      of stem cells and induction of tumours resembling human adamantinomatous
      craniopharyngioma (ACP), derived from Sox2- cells in a paracrine manner. Here, we
      uncover the mechanisms underlying this paracrine tumourigenesis. We show that
      expression of oncogenic beta-catenin in Hesx1+ embryonic precursors also results
      in stem cell clusters and paracrine tumours. We reveal that human and mouse
      clusters are analogous and share a common signature of senescence and SASP.
      Finally, we show that mice with reduced senescence and SASP responses exhibit
      decreased tumour-inducing potential. Together, we provide evidence that
      senescence and a stem cell-associated SASP drive cell transformation and tumour
      initiation in vivo in an age-dependent fashion.

PMID- 29180746
TI  - NumtS colonization in mammalian genomes.
AB  - The colonization of the nuclear genome by mitochondrial DNA is an ongoing process
      in eukaryotes and plays an important role in genomic variability. Notwithstanding
      the DNA sequence availability of about 100 complete eukaryotic genomes, up to now
      NumtS distribution has been fully reported for a small number of sequenced
      eukaryotic species. With the aim to clarify the time and way of NumtS evolution,
      we explored the genomic distribution of NumtS in 23 eukaryotic species using an
      intra/interspecies in silico approach based on a cross-species similarity search
      and deeply investigate the evolution of NumtS in mammals. The intra- and
      interspecies analysis underlined how some mitochondrial regions that populated
      nuclear genomes can be considered as hotspots. Considering the large amount of
      NumtS we found in platypus and opossum genomes, we hypothesized the occurrence of
      an earlier colonization that happened prior to the Prototherian/Therian mammal
      divergence, approximately 160-210 million years ago. These events are still
      detectable due to the species-specific dynamics that have affected these genomes.
      Phylogenetic analyses of NumtS derived from two different mitochondrial DNA loci
      allowed us to recognize the unusual NumtS evolution that acted differently on
      primate and non-primate species' genomes.

PMID- 29180747
TI  - Accumbal D2 cells orchestrate innate risk-avoidance according to orexin signals.
AB  - Excitation of accumbal D2 cells governs vital actions, including avoidance of
      learned risks, but the origins of this excitation and roles of D2 cells in innate
      risk-avoidance are unclear. Hypothalamic neurons producing orexins (also called
      hypocretins) enhance innate risk-avoidance via poorly understood neurocircuits.
      We describe a direct orexin->D2 excitatory circuit and show that D2 cell activity
      is necessary for orexin-dependent innate risk-avoidance in mice, thus revealing
      an unsuspected hypothalamus-accumbens interplay in action selection.

PMID- 29180748
TI  - Altered responses to social chemosignals in autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is characterized by impaired social communication,
      often attributed to misreading of emotional cues. Why individuals with ASD
      misread emotions remains unclear. Given that terrestrial mammals rely on their
      sense of smell to read conspecific emotions, we hypothesized that misreading of
      emotional cues in ASD partially reflects altered social chemosignaling. We found
      no difference between typically developed (TD) and cognitively able adults with
      ASD at explicit detection and perception of social chemosignals. Nevertheless, TD
      and ASD participants dissociated in their responses to subliminal presentation of
      these same compounds: the undetected 'smell of fear' (skydiver sweat) increased
      physiological arousal and reduced explicit and implicit measures of trust in TD
      but acted opposite in ASD participants. Moreover, two different undetected
      synthetic putative social chemosignals increased or decreased arousal in TD but
      acted opposite in ASD participants. These results implicate social chemosignaling
      as a sensory substrate of social impairment in ASD.

PMID- 29180749
TI  - Clonal evolution and antigen recognition of anti-nuclear antibodies in acute
      systemic lupus erythematosus.
AB  - The evolutional process of disease-associated autoantibodies in systemic lupus
      erythematosus (SLE) remains to be established. Here we show intraclonal
      diversification and affinity maturation of anti-nuclear antibody (ANA)-producing
      B cells in SLE. We identified a panel of monoclonal ANAs recognizing nuclear
      antigens, such as double-stranded DNA (dsDNA) and ribonucleoproteins (RNPs) from
      acute SLE subjects. These ANAs had relatively few, but nonetheless critical
      mutations. High-throughput immunoglobulin sequencing of blood lymphocytes
      disclosed the existence of sizable ANA lineages shearing critical mutations
      intraclonally. We further focused on anti-DNA antibodies, which are capable to
      bind to both single-stranded (ss) and dsDNA at high affinity. Crystal structure
      and biochemical analysis confirmed a direct role of the mutations in the
      acquisition of DNA reactivity and also revealed that these anti-DNA antibodies
      recognized an unpaired region within DNA duplex. Our study unveils the unique
      properties of high-affinity anti-DNA antibodies that are generated through
      antigen-driven affinity maturation in acute phase of SLE.

PMID- 29180751
TI  - Quantum algorithm for preparing the ground state of a system via resonance
      transition.
AB  - Preparing the ground state of a system is an important task in physics. We
      propose a quantum algorithm for preparing the ground state of a physical system
      that can be simulated on a quantum computer. The system is coupled to an
      ancillary qubit, by introducing a resonance mechanism between the ancilla qubit
      and the system, and combined with measurements performed on the ancilla qubit,
      the system can be evolved to monotonically converge to its ground state through
      an iterative procedure. We have simulated the application of this algorithm for
      the Afflect-Kennedy-Lieb-Tasaki model, whose ground state can be used as resource
      state in one-way quantum computation.

PMID- 29180750
TI  - Strain-resolved analysis of hospital rooms and infants reveals overlap between
      the human and room microbiome.
AB  - Preterm infants exhibit different microbiome colonization patterns relative to
      full-term infants, and it is speculated that the hospital room environment may
      contribute to infant microbiome development. Here, we present a genome-resolved
      metagenomic study of microbial genotypes from the gastrointestinal tracts of
      infants and from the neonatal intensive care unit (NICU) room environment. Some
      strains detected in hospitalized infants also occur in sinks and on surfaces, and
      belong to species such as Staphylococcus epidermidis, Enterococcus faecalis,
      Pseudomonas aeruginosa, and Klebsiella pneumoniae, which are frequently
      implicated in nosocomial infection and preterm infant gut colonization. Of the 15
      K. pneumoniae strains detected in the study, four were detected in both infant
      gut and room samples. Time series experiments showed that nearly all strains
      associated with infant gut colonization can be detected in the room after, and
      often before, detection in the gut. Thus, we conclude that a component of
      premature infant gut colonization is the cycle of microbial exchange between the
      room and the occupant.

PMID- 29180752
TI  - The E. coli dicarboxylic acid transporters DauA act as a signal transducer by
      interacting with the DctA uptake system.
AB  - The Slc26A/SulP family of ions transporter is ubiquitous and widpsread in all
      kingdon of life. In E. coli, we have demonstrated that the Slc26 protein DauA is
      a C4-dicarboxilic acids (C4-diC) transporter active at acidic pH. The main C4-diC
      transporter active at pH7 is DctA and is induced by C4-diC via the DcuS/R two
      component system. DctA interacts with DcuS, the membrane embedded histidine
      kinase, to transfers DcuS to the responsive state, i.e. in the absence of DctA,
      DcuS is permanently "on", but its activity is C4-diC-dependent when in complex
      with DctA. Using phenotypic characterization, transport assays and protein
      expression studies, we show that at pH7 full DctA production depends on the
      presence of DauA. A Bacterial Two Hybrid system indicates that DauA and the
      sensor complex DctA/DcuS physically interact at the membrane. Pull down
      experiments completed by co-purification study prove that DauA and DctA interact
      physically at the membrane. These data open a completely new aspect of the C4-diC
      metabolism in E. coli and reveals how the bacterial Slc26A uptake systems
      participate in multiple cellular functions. This constitutes a new example of a
      bacterial transporter that acts as a processor in a transduction pathway.

PMID- 29180753
TI  - Dissipative quantum error correction and application to quantum sensing with
      trapped ions.
AB  - Quantum-enhanced measurements hold the promise to improve high-precision sensing
      ranging from the definition of time standards to the determination of fundamental
      constants of nature. However, quantum sensors lose their sensitivity in the
      presence of noise. To protect them, the use of quantum error-correcting codes has
      been proposed. Trapped ions are an excellent technological platform for both
      quantum sensing and quantum error correction. Here we present a quantum error
      correction scheme that harnesses dissipation to stabilize a trapped-ion qubit. In
      our approach, always-on couplings to an engineered environment protect the qubit
      against spin-flips or phase-flips. Our dissipative error correction scheme
      operates in a continuous manner without the need to perform measurements or
      feedback operations. We show that the resulting enhanced coherence time
      translates into a significantly enhanced precision for quantum measurements. Our
      work constitutes a stepping stone towards the paradigm of self-correcting quantum
      information processing.

PMID- 29180754
TI  - Complexity and conflicts of interest statements: a case-study of emails exchanged
      between Coca-Cola and the principal investigators of the International Study of
      Childhood Obesity, Lifestyle and the Environment (ISCOLE).
AB  - Statements on conflicts of interest provide important information for readers of
      scientific papers. There is now compelling evidence from several fields that
      papers reporting funding from organizations that have an interest in the results
      often generate different findings from those that do not report such funding. We
      describe the findings of an analysis of correspondence between representatives of
      a major soft drinks company and scientists researching childhood obesity.
      Although the studies report no influence by the funder, the correspondence
      describes detailed exchanges on the study design, presentation of results and
      acknowledgement of funding. This raises important questions about the meaning of
      standard statements on conflicts of interest.

PMID- 29180755
TI  - Nav channel binder containing a specific conjugation-site based on a low toxicity
      beta-scorpion toxin.
AB  - Voltage-gated sodium (Nav) channels play a key role in generating action
      potentials which leads to physiological signaling in excitable cells. The
      availability of probes for functional studies of mammalian Nav is limited. Here,
      by introducing two amino acid substitutions into the beta scorpion toxin Ts1, we
      have chemically synthesized a novel binder [S14R, W50Pra]Ts1 for Nav with high
      affinity, low dissociation rate and reduced toxicity while retaining the
      capability of conjugating Ts1 with molecules of interests for different
      applications. Using the fluorescent-dye conjugate, [S14R, W50Pra(Bodipy)]Ts1, we
      confirmed its binding to Nav1.4 through Lanthanide-based Resonance Energy
      Transfer. Moreover, using the gold nanoparticle conjugate, [S14R,
      W50Pra(AuNP)]Ts1, we were able to optically stimulate dorsal root ganglia neurons
      and generate action potentials with visible light via the optocapacitive effect
      as previously reported. [S14R, W50Pra]Ts1 is a novel probe with great potential
      for wider applications in Nav-related neuroscience research.

PMID- 29180756
TI  - Asymmetrical bipolar nanosecond electric pulse widths modify bipolar
      cancellation.
AB  - A bipolar (BP) nanosecond electric pulse (nsEP) exposure generates reduced
      calcium influx compared to a unipolar (UP) nsEP. This attenuated physiological
      response from a BP nsEP exposure is termed "bipolar cancellation" (BPC). The
      predominant BP nsEP parameters that induce BPC consist of a positive polarity (?)
      front pulse followed by the delivery of a negative polarity (?) back pulse of
      equal voltage and width; thereby the duration is twice a UP nsEP exposure. We
      tested these BPC parameters, and discovered that a BP nsEP with symmetrical pulse
      widths is not required to generate BPC. For example, our data revealed the
      physiological response initiated by a ?900 nsEP exposure can be cancelled by a
      second pulse that is a third of its duration.  However, we observed a complete
      loss of BPC from a ?300 nsEP followed by a ?900 nsEP exposure. Spatiotemporal
      analysis revealed these asymmetrical BP nsEP exposures generate distinct local YO
      PRO(r)-1 uptake patterns across the plasma membrane. From these findings, we
      generated a conceptual model that suggests BPC is a phenomenon balanced by
      localized charging and discharging events across the membrane.

PMID- 29180757
TI  - Discovery of High-Affinity PDGF-VEGFR Interactions: Redefining RTK Dynamics.
AB  - Nearly all studies of angiogenesis have focused on uni-family ligand-receptor
      binding, e.g., VEGFs bind to VEGF receptors, PDGFs bind to PDGF receptors, etc.
      The discovery of VEGF-PDGFRs binding challenges this paradigm and calls for
      investigation of other ligand-receptor binding possibilities. We utilized surface
      plasmon resonance to identify and measure PDGF-to-VEGFR binding rates,
      establishing cut-offs for binding and non-binding interactions. We quantified the
      kinetics of the recent VEGF-A:PDGFRbeta interaction for the first time with KD =
      340 pM. We discovered new PDGF:VEGFR2 interactions with PDGF-AA:R2 KD = 530 nM,
      PDGF-AB:R2 KD = 110 pM, PDGF-BB:R2 KD = 40 nM, and PDGF-CC:R2 KD = 70 pM. We
      computationally predict that cross-family PDGF binding could contribute up to 96%
      of VEGFR2 ligation in healthy conditions and in cancer. Together the
      identification, quantification, and simulation of these novel cross-family
      interactions posits new mechanisms for understanding anti-angiogenic drug
      resistance and presents an expanded role of growth factor signaling with
      significance in health and disease.

PMID- 29180758
TI  - Knowledge graph prediction of unknown adverse drug reactions and validation in
      electronic health records.
AB  - Unknown adverse reactions to drugs available on the market present a significant
      health risk and limit accurate judgement of the cost/benefit trade-off for
      medications. Machine learning has the potential to predict unknown adverse
      reactions from current knowledge. We constructed a knowledge graph containing
      four types of node: drugs, protein targets, indications and adverse reactions.
      Using this graph, we developed a machine learning algorithm based on a simple
      enrichment test and first demonstrated this method performs extremely well at
      classifying known causes of adverse reactions (AUC 0.92). A cross validation
      scheme in which 10% of drug-adverse reaction edges were systematically deleted
      per fold showed that the method correctly predicts 68% of the deleted edges on
      average. Next, a subset of adverse reactions that could be reliably detected in
      anonymised electronic health records from South London and Maudsley NHS
      Foundation Trust were used to validate predictions from the model that are not
      currently known in public databases. High-confidence predictions were validated
      in electronic records significantly more frequently than random models, and
      outperformed standard methods (logistic regression, decision trees and support
      vector machines). This approach has the potential to improve patient safety by
      predicting adverse reactions that were not observed during randomised trials.

PMID- 29180760
TI  - Detectability of Breast Tumor by a Hand-held Impulse-Radar Detector: Performance
      Evaluation and Pilot Clinical Study.
AB  - In this report, a hand-held impulse-radar breast cancer detector is presented and
      the detectability of malignant breast tumors is demonstrated in the clinical test
      at Hiroshima University Hospital, Hiroshima, Japan. The core functional parts of
      the detector consist of 65-nm technology complementary metal-oxide-semiconductor
      (CMOS) integrated circuits covering the ultrawideband width from 3.1 to 10.6 GHz,
      which enable the generation and transmission of Gaussian monocycle pulse (GMP)
      with the pulse width of 160 ps and single port eight throw (SP8T) switching
      matrices for controlling the combination of 4 * 4 cross-shaped dome antenna
      array. The detector is designed to be placed on the breast with the patient in
      the supine position. The detectability of malignant tumors is confirmed in
      excised breast tissues after total mastectomy surgery. The three-dimensional
      positions of the tumors in the imaging results are consistent with the results of
      histopathology analysis. The clinical tests are conducted by a clinical doctor
      for five patients at the hospital. The malignant tumors include invasive ductal
      carcinoma (IDC) and ductal carcinoma in situ (DCIS). The final confocal imaging
      results are consistent with those of Magnetic Resonance Imaging (MRI),
      demonstrating the feasibility of the hand-held impulse-radar detector for
      malignant breast tumors.

PMID- 29180759
TI  - Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and
      reversing immunosuppression.
AB  - While chemotherapy delivery by nanocarriers has modestly improved the survival
      prospects of pancreatic ductal adenocarcinoma (PDAC), additional engagement of
      the immune response could be game changing. We demonstrate a nano-enabled
      approach for accomplishing robust anti-PDAC immunity in syngeneic mice through
      the induction of immunogenic cell death (ICD) as well as interfering in the
      immunosuppressive indoleamine 2,3-dioxygenase (IDO) pathway. This is accomplished
      by conjugating the IDO inhibitor, indoximod (IND), to a phospholipid that allows
      prodrug self-assembly into nanovesicles or incorporation into a lipid bilayer
      that encapsulates mesoporous silica nanoparticles (MSNP). The porous MSNP
      interior allows contemporaneous delivery of the ICD-inducing chemotherapeutic
      agent, oxaliplatin (OX). The nanovesicles plus free OX or OX/IND-MSNP induce
      effective innate and adaptive anti-PDAC immunity when used in a vaccination
      approach, direct tumor injection or intravenous biodistribution to an orthotopic
      PDAC site. Significant tumor reduction or eradication is accomplishable by
      recruiting cytotoxic T lymphocytes, concomitant with downregulation of Foxp3+ T
      cells.

PMID- 29180761
TI  - Combined inhibition of MEK and nuclear ERK translocation has synergistic
      antitumor activity in melanoma cells.
AB  - Genetic alterations in BRAF, NRAS and NF1 that activate the ERK cascade, account
      for over 80% of metastatic melanomas. However, ERK cascade inhibitors have been
      proven beneficial almost exclusively for BRAF mutant melanomas. One of the
      hallmarks of the ERK cascade is the nuclear translocation of ERK1/2, which is
      important mainly for the induction of proliferation. This translocation can be
      inhibited by the NTS-derived peptide (EPE) that blocks the ERK1/2-importin7
      interaction, inhibits the nuclear translocation of ERK1/2, and arrests active
      ERK1/2 in the cytoplasm. In this study, we found that the EPE peptide
      significantly reduced the viability of not only BRAF, but also several NRAS and
      NF1 mutant melanomas. Importantly, combination of the EPE peptide and trametinib
      showed synergy in reducing the viability of some NRAS mutant melanomas, an effect
      driven by the partial preservation of negative feedback loops. The same
      combination significantly reduced the viability of other melanoma cells,
      including those resistant to mono-treatment with EPE peptide and ERK cascade
      inhibitors. Our study indicates that targeting the nuclear translocation of
      ERK1/2, in combination with MEK inhibitors can be used for the treatment of
      different mutant melanomas.

PMID- 29180762
TI  - Linear magnetoelectric effect in gothite, alpha-FeOOH.
AB  - By means of symmetry analysis, density functional theory calculations, and Monte
      Carlo simulations we show that goethite, alpha-FeOOH, is a linear magnetoelectric
      below its Neel temperature T N = 400 K. The experimentally observed magnetic
      field induced spin-flop phase transition results in either change of direction of
      electric polarization or its suppression. Estimated value of magnetoelectric
      coefficient is 0.57 MUC . m-2 . T-1. The abundance of goethite in nature makes it
      arguably the most widespread magnetoelectric material.

PMID- 29180763
TI  - Identification of genes expressed in a mesenchymal subset regulating prostate
      organogenesis using tissue and single cell transcriptomics.
AB  - Prostate organogenesis involves epithelial growth controlled by inductive
      signalling from specialised mesenchymal subsets. To identify pathways active in
      mesenchyme we used tissue and single cell transcriptomics to define mesenchymal
      subsets and subset-specific transcript expression. We documented transcript
      expression using Tag-seq and RNA-seq in female rat Ventral Mesenchymal Pad (VMP)
      as well as adjacent urethra comprised of smooth muscle and peri-urethral
      mesenchyme. Transcripts enriched in female VMP were identified with Tag-seq of
      microdissected tissue, RNA-seq of cell populations, and single cells. We
      identified 400 transcripts as enriched in the VMP using bio-informatic
      comparisons of Tag-seq and RNA-seq data, and 44 were confirmed by single cell RNA
      seq. Cell subset analysis showed that VMP and adjacent mesenchyme were composed
      of distinct cell types and that each tissue contained two subgroups. Markers for
      these subgroups were highly subset specific. Thirteen transcripts were validated
      by qPCR to confirm cell specific expression in microdissected tissues, as well as
      expression in neonatal prostate. Immunohistochemical staining demonstrated that
      Ebf3 and Meis2 showed a restricted expression pattern in female VMP and prostate
      mesenchyme. We conclude that prostate inductive mesenchyme shows limited cellular
      heterogeneity and that transcriptomic analysis identified new mesenchymal subset
      transcripts associated with prostate organogenesis.

PMID- 29180764
TI  - Synthesis and implication of novel poly(acrylic acid)/nanosorbent embedded
      hydrogel composite for lead ion removal.
AB  - Lead stands second among the deadly heavy metal pollutants owing to the
      incompetent mechanism possessed by the human body for its removal. A polymeric
      hydrogel in the form of composite was prepared using acrylic acid (monomer) and
      novel nanofiller that possess super adsorbent properties with restricted gel
      seepage into flowing ionic liquid. The filler used is an adsorbent which is
      biocompatible, biodegradable, economical, abundant, non-hazardous and easy to
      synthesize. The invariably porous nanofiller, the Nanobentonite(clay), was
      synthesized using ion exchange reaction by creating acidic environment for
      accelerated dispersion with exfoliation by CTAB to enhance cation exchange
      capacity. NanobentoFnite was capable of removing >97% lead ion in batch
      adsorption study and followed pseudo-second order kinetic model. Freundlich
      isotherm suggested a removal capacity of ~20 mg/g. Thus, the successfully
      experimented adsorbent was implicated as filler to form polyacrylic acid nanoclay
      hydrogel polymerized in ultrasonic bath. The amount of filler was varied from
      0.25 to 2 wt% to get 94% removal, analyzed using ICP-OES. The prepared adsorbents
      were characterized before and after adsorption using TEM, FESEM, XRD, FTIR and
      DSC to understand the structural changes and metal-sorbent interaction. Thus, the
      novel nanosorbent/composite are promiscuous and competent in terms of
      availability, reusability and longevity to remove heavy metal ions.

PMID- 29180765
TI  - The inhibitory effect of minocycline on radiation-induced neuronal apoptosis via
      AMPKalpha1 signaling-mediated autophagy.
AB  - Due to an increasing concern about radiation-induced cognitive deficits for brain
      tumor patients receiving radiation therapy, developing and evaluating
      countermeasures has become inevitable. Our previous study has found that
      minocycline, a clinical available antibiotics that can easily cross the blood
      brain barrier, mitigates radiation-induced long-term memory loss in rats,
      accompanied by decreased hippocampal neuron apoptosis. Thus, in the present
      study, we report an unknown mechanism underlying the neuroprotective effect of
      minocycline. We demonstrated that minocycline prevented primary neurons from
      radiation-induced apoptosis and promoted radiation-induced autophagy in vitro.
      Moreover, using an immortalized mouse hippocampal neuronal cell line, HT22 cells,
      we found that the protective effect of minocycline on irradiated HT22 cells was
      not related to DNA damage repair since minocycline did not facilitate DNA DSB
      repair in irradiated HT22 cells. Further investigation showed that minocycline
      significantly enhanced X-irradiation-induced AMPKalpha1 activation and autophagy,
      thus resulting in decreased apoptosis. Additionally, although the antioxidant
      potential of minocycline might contribute to its apoptosis-inhibitory effect, it
      was not involved in its enhancive effect on radiation-induced AMPKalpha1-mediated
      autophagy. Taken together, we have revealed a novel mechanism for the protective
      effect of minocycline on irradiated neurons, e.g. minocycline protects neurons
      from radiation-induced apoptosis via enhancing radiation-induced AMPKalpha1
      mediated autophagy.

PMID- 29180768
TI  - Screening for pulmonary hypertension in preterm infants-not ready for prime time.

PMID- 29180767
TI  - Frequency and reactivity of antigen-specific T cells were concurrently measured
      through the combination of artificial antigen-presenting cell, MACS and ELISPOT.
AB  - Conventional peptide-major histocompatibility complex (pMHC) multimer staining,
      intracellular cytokine staining, and enzyme-linked immunospot (ELISPOT) assay
      cannot concurrently determine the frequency and reactivity of antigen-specific T
      cells (AST) in a single assay. In this report, pMHC multimer, magnetic-activated
      cell sorting (MACS), and ELISPOT techniques have been integrated into a micro
      well by coupling pMHC multimers onto cell-sized magnetic beads to characterize
      AST cell populations in a 96-well microplate which pre-coated with cytokine
      capture antibodies. This method, termed AAPC-microplate, allows the enumeration
      and local cytokine production of AST cells in a single assay without using flow
      cytometry or fluorescence intensity scanning, thus will be widely applicable.
      Here, ovalbumin257-264-specific CD8+ T cells from OT-1 T cell receptor (TCR)
      transgenic mice were measured. The methodological accuracy, specificity,
      reproducibility, and sensitivity in enumerating AST cells compared well with
      conventional pMHC multimer staining. Furthermore, the AAPC-microplate was applied
      to detect the frequency and reactivity of Hepatitis B virus (HBV) core antigen18
      27- and surface antigen183-191-specific CD8+ T cells for the patients, and was
      compared with conventional method. This method without the need of high-end
      instruments may facilitate the routine analysis of patient-specific cellular
      immune response pattern to a given antigen in translational studies.

PMID- 29180766
TI  - Oscillatory brain activity in spontaneous and induced sleep stages in flies.
AB  - Sleep is a dynamic process comprising multiple stages, each associated with
      distinct electrophysiological properties and potentially serving different
      functions. While these phenomena are well described in vertebrates, it is unclear
      if invertebrates have distinct sleep stages. We perform local field potential
      (LFP) recordings on flies spontaneously sleeping, and compare their brain
      activity to flies induced to sleep using either genetic activation of sleep
      promoting circuitry or the GABAA agonist Gaboxadol. We find a transitional sleep
      stage associated with a 7-10 Hz oscillation in the central brain during
      spontaneous sleep. Oscillatory activity is also evident when we acutely activate
      sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila. In
      contrast, sleep following Gaboxadol exposure is characterized by low-amplitude
      LFPs, during which dFB-induced effects are suppressed. Sleep in flies thus
      appears to involve at least two distinct stages: increased oscillatory activity,
      particularly during sleep induction, followed by desynchronized or decreased
      brain activity.

PMID- 29180769
TI  - Performance on emotional tasks engaging cognitive control depends on emotional
      intelligence abilities: an ERP study.
AB  - Cognitive control is a key process in decision making and adequately adapting our
      behavior to the environment. Previous studies have provided evidence of a lower
      capacity for cognitive control in emotion-laden contexts in comparison with
      neutral contexts. The aim of the present research was to study changes in
      cognitive control performance as a function of emotional intelligence (EI) level
      in contexts involving emotional information. The study sample was composed of 2
      groups of 22 participants each: the high and low EI group. Participants carried
      out an emotional go/no-go task while brain activity was recorded by EEG. N2 and
      P3 ERPs were used as indices of cognitive control processing. Participants with
      higher EI showed a larger N2, reflecting a greater capacity for cognitive control
      related to changes in conflict monitoring, and to a better detection and
      evaluation of the emotional stimuli. Moreover, in general, response inhibition
      accuracy was reduced when emotional information was involved in this process. Our
      findings reveal that neural mechanisms underlying tasks that engage cognitive
      control depend on emotional content and EI level. This study indicates the
      important role played by EI in the relationship between emotion and cognition. EI
      training may be a very useful tool for improving performance in emotion-laden
      contexts.

PMID- 29180770
TI  - Optical gain in colloidal quantum dots achieved with direct-current electrical
      pumping.
AB  - Chemically synthesized semiconductor quantum dots (QDs) can potentially enable
      solution-processable laser diodes with a wide range of operational wavelengths,
      yet demonstrations of lasing from the QDs are still at the laboratory stage. An
      important challenge-realization of lasing with electrical injection-remains
      unresolved, largely due to fast nonradiative Auger recombination of multicarrier
      states that represent gain-active species in the QDs. Here we present population
      inversion and optical gain in colloidal nanocrystals realized with direct-current
      electrical pumping. Using continuously graded QDs, we achieve a considerable
      suppression of Auger decay such that it can be outpaced by electrical injection.
      Further, we apply a special current-focusing device architecture, which allows us
      to produce high current densities (j) up to ~18 A cm-2 without damaging either
      the QDs or the injection layers. The quantitative analysis of electroluminescence
      and current-modulated transmission spectra indicates that with j = 3-4 A cm-2 we
      achieve the population inversion of the band-edge states.

PMID- 29180771
TI  - Programmed coherent coupling in a synthetic DNA-based excitonic circuit.
AB  - Natural light-harvesting systems spatially organize densely packed chromophore
      aggregates using rigid protein scaffolds to achieve highly efficient, directed
      energy transfer. Here, we report a synthetic strategy using rigid DNA scaffolds
      to similarly program the spatial organization of densely packed, discrete
      clusters of cyanine dye aggregates with tunable absorption spectra and strongly
      coupled exciton dynamics present in natural light-harvesting systems. We first
      characterize the range of dye-aggregate sizes that can be templated spatially by
      A-tracts of B-form DNA while retaining coherent energy transfer. We then use
      structure-based modelling and quantum dynamics to guide the rational design of
      higher-order synthetic circuits consisting of multiple discrete dye aggregates
      within a DX-tile. These programmed circuits exhibit excitonic transport
      properties with prominent circular dichroism, superradiance, and fast delocalized
      exciton transfer, consistent with our quantum dynamics predictions. This bottom
      up strategy offers a versatile approach to the rational design of strongly
      coupled excitonic circuits using spatially organized dye aggregates for use in
      coherent nanoscale energy transport, artificial light-harvesting, and
      nanophotonics.

PMID- 29180772
TI  - Dislocation nucleation facilitated by atomic segregation.
AB  - Surface segregation-the enrichment of one element at the surface, relative to the
      bulk-is ubiquitous to multi-component materials. Using the example of a Cu-Au
      solid solution, we demonstrate that compositional variations induced by surface
      segregation are accompanied by misfit strain and the formation of dislocations in
      the subsurface region via a surface diffusion and trapping process. The resulting
      chemically ordered surface regions acts as an effective barrier that inhibits
      subsequent dislocation annihilation at free surfaces. Using dynamic, atomic-scale
      resolution electron microscopy observations and theory modelling, we show that
      the dislocations are highly active, and we delineate the specific atomic-scale
      mechanisms associated with their nucleation, glide, climb, and annihilation at
      elevated temperatures. These observations provide mechanistic detail of how
      dislocations nucleate and migrate at heterointerfaces in dissimilar-material
      systems.

PMID- 29180773
TI  - Chiral liquid crystal colloids.
AB  - Colloidal particles disturb the alignment of rod-like molecules of liquid
      crystals, giving rise to long-range interactions that minimize the free energy of
      distorted regions. Particle shape and topology are known to guide this self
      assembly process. However, how chirality of colloidal inclusions affects these
      long-range interactions is unclear. Here we study the effects of distortions
      caused by chiral springs and helices on the colloidal self-organization in a
      nematic liquid crystal using laser tweezers, particle tracking and optical
      imaging. We show that chirality of colloidal particles interacts with the nematic
      elasticity to predefine chiral or racemic colloidal superstructures in nematic
      colloids. These findings are consistent with numerical modelling based on the
      minimization of Landau-de Gennes free energy. Our study uncovers the role of
      chirality in defining the mesoscopic order of liquid crystal colloids, suggesting
      that this feature may be a potential tool to modulate the global orientated self
      organization of these systems.

PMID- 29180774
TI  - Spontaneous exchange bias formation driven by a structural phase transition in
      the antiferromagnetic material.
AB  - Most of the magnetic devices in advanced electronics rely on the exchange bias
      effect, a magnetic interaction that couples a ferromagnetic and an
      antiferromagnetic material, resulting in a unidirectional displacement of the
      ferromagnetic hysteresis loop by an amount called the 'exchange bias field'.
      Setting and optimizing exchange bias involves cooling through the Neel
      temperature of the antiferromagnetic material in the presence of a magnetic
      field. Here we demonstrate an alternative process for the generation of exchange
      bias. In IrMn/FeCo bilayers, a structural phase transition in the IrMn layer
      develops at room temperature, exchange biasing the FeCo layer as it propagates.
      Once the process is completed, the IrMn layer contains very large single-crystal
      grains, with a large density of structural defects within each grain, which are
      promoted by the FeCo layer. The magnetic characterization indicates that these
      structural defects in the antiferromagnetic layer are behind the resulting large
      value of the exchange bias field and its good thermal stability. This mechanism
      for establishing the exchange bias in such a system can contribute towards the
      clarification of fundamental aspects of this exchange interaction.

PMID- 29180775
TI  - Ubiquitous formation of bulk Dirac cones and topological surface states from a
      single orbital manifold in transition-metal dichalcogenides.
AB  - Transition-metal dichalcogenides (TMDs) are renowned for their rich and varied
      bulk properties, while their single-layer variants have become one of the most
      prominent examples of two-dimensional materials beyond graphene. Their disparate
      ground states largely depend on transition metal d-electron-derived electronic
      states, on which the vast majority of attention has been concentrated to date.
      Here, we focus on the chalcogen-derived states. From density-functional theory
      calculations together with spin- and angle-resolved photoemission, we find that
      these generically host a co-existence of type-I and type-II three-dimensional
      bulk Dirac fermions as well as ladders of topological surface states and surface
      resonances. We demonstrate how these naturally arise within a single p-orbital
      manifold as a general consequence of a trigonal crystal field, and as such can be
      expected across a large number of compounds. Already, we demonstrate their
      existence in six separate TMDs, opening routes to tune, and ultimately exploit,
      their topological physics.

PMID- 29180777
TI  - Colloidal nanocrystals: Electrifying quantum dots for lasers.

PMID- 29180776
TI  - Temporary formation of highly conducting domain walls for non-destructive read
      out of ferroelectric domain-wall resistance switching memories.
AB  - Erasable conductive domain walls in insulating ferroelectric thin films can be
      used for non-destructive electrical read-out of the polarization states in
      ferroelectric memories. Still, the domain-wall currents extracted by these
      devices have not yet reached the intensity and stability required to drive read
      out circuits operating at high speeds. This study demonstrated non-destructive
      read-out of digital data stored using specific domain-wall configurations in
      epitaxial BiFeO3 thin films formed in mesa-geometry structures. Partially
      switched domains, which enable the formation of conductive walls during the read
      operation, spontaneously retract when the read voltage is removed, reducing the
      accumulation of mobile defects at the domain walls and potentially improving the
      device stability. Three-terminal memory devices produced 14 nA read currents at
      an operating voltage of 5 V, and operated up to T = 85  degrees C. The gap length
      can also be smaller than the film thickness, allowing the realization of
      ferroelectric memories with device dimensions far below 100 nm.

PMID- 29180778
TI  - The development of bioresorbable composite polymeric implants with high
      mechanical strength.
AB  - Implants for the treatment of tissue defects should mimic the mechanical
      properties of the native tissue of interest and should be resorbable as well as
      biocompatible. In this work, we developed a scaffold from variants of
      poly(glycolic) acid which were braided and coated with an elastomer of
      poly(glycolide-co-caprolactone) and crosslinked. The coating of the scaffold with
      the elastomer led to higher mechanical strength in terms of compression,
      expansion and elasticity compared to braids without the elastomer coating. These
      composite scaffolds were found to have expansion properties similar to metallic
      stents, utilizing materials which are typically much weaker than metal. We
      optimized the mechanical properties of the implant by tuning the elastomer
      branching structure, crosslink density, and molecular weight. The scaffolds were
      shown to be highly resorbable following implantation in a porcine femoral artery.
      Biocompatibility was studied in vivo in an ovine model by implanting the
      scaffolds into femoral arteries. The scaffolds were able to support an expanded
      open lumen over 12 months in vivo and also fully resorbed by 18 months in the
      ovine model.

PMID- 29180779
TI  - Plating and stripping calcium in an organic electrolyte.
AB  - There is considerable interest in multivalent cation batteries, such as those
      based on magnesium, calcium or aluminium. Most attention has focused on
      magnesium. In all cases the metal anode represents a significant challenge.
      Recent work has shown that calcium can be plated and stripped, but only at
      elevated temperatures, 75 to 100  degrees C, with small capacities, typically
      0.165 mAh cm-2, and accompanied by significant side reactions. Here we
      demonstrate that calcium can be plated and stripped at room temperature with
      capacities of 1 mAh cm-2 at a rate of 1 mA cm-2, with low polarization (~100 mV)
      and in excess of 50 cycles. The dominant product is calcium, accompanied by a
      small amount of CaH2 that forms by reaction between the deposited calcium and the
      electrolyte, Ca(BH4)2 in tetrahydrofuran (THF). This occurs in preference to the
      reactions which take place in most electrolyte solutions forming CaCO3, Ca(OH)2
      and calcium alkoxides, and normally terminate the electrochemistry. The CaH2
      protects the calcium metal at open circuit. Although this work does not solve all
      the problems of calcium as an anode in calcium-ion batteries, it does demonstrate
      that significant quantities of calcium can be plated and stripped at room
      temperature with low polarization.

PMID- 29180780
TI  - In situ investigation of phase transformations in Ti-6Al-4V under additive
      manufacturing conditions combining laser melting and high-speed micro-X-ray
      diffraction.
AB  - We present combined in situ X-ray diffraction and high-speed imaging to monitor
      the phase evolution upon cyclic rapid laser heating and cooling mimicking the
      direct energy deposition of Ti-6Al-4V in real time. Additive manufacturing of the
      industrially relevant alloy Ti-6Al-4V is known to create a multitude of phases
      and microstructures depending on processing technology and parameters. Current
      setups are limited by an averaged measurement through the solid and liquid parts.
      In this work the combination of a micro-focused intense X-ray beam, a fast
      detector and unidirectional cooling provide the spatial and temporal resolution
      to separate contributions from solid and liquid phases in limited volumes. Upon
      rapid heating and cooling, the beta <-> alpha' phase transformation is observed
      repeatedly. At room temperature, single phase alpha' is observed. Secondary beta
      formation upon formation of alpha' is attributed to V partitioning to the beta
      phase leading to temporary stabilization. Lattice strains in the alpha'-phase are
      found to be sensitive to the alpha' -> beta phase transformation. Based on
      lattice strain of the beta-phase, the martensite start temperature is estimated
      at 923 K in these experiments. Off-axis high speed imaging confirms a technically
      relevant solidification front velocity and cooling rate of 10.3 mm/s and 4500
      K/s, respectively.

PMID- 29180781
TI  - The Relationship between Secondary Forest and Environmental Factors in the
      Southern Taihang Mountains.
AB  - It is important to understand the effects of environmental factors on secondary
      forest assembly for effective afforestation and vegetation restoration. We
      studied 24 20 m * 20 m quadrats of natural secondary forest in the southern
      Taihang Mountains. Canonical correspondence analysis (CCA) and two-way indicator
      hydrocarbon analysis were used to analyse the relationship between community
      vegetation and environmental factors. The CCA showed that 13 terrain and soil
      variables shared 68.17% of the total variance. The principal environmental
      variables, based on the most parsimonious CCA model, were (in order) elevation,
      soil total N, soil gravel content, slope, soil electrical conductivity, and pH.
      Samples were clustered into four forest types, with forest diversity affected by
      elevation, nutrients, and water gradients. Topographical variables affected
      forest assembly more than soil variables. Species diversity was evaluated using
      the Shannon-Wiener, Simpson's diversity, and Pielou's evenness indexes. The
      environmental factors that affected species distribution had different effects on
      species diversity. The vegetation-environment relationship in the southern region
      was different than the central region of the Taihang Mountains, and vegetation
      restoration was at an early stage. The terrain of the southern region, especially
      elevation and slope, should be considered for vegetation restoration and
      conservation.

PMID- 29180782
TI  - Alpha-helicoidal HEAT-like Repeat Proteins (alphaRep) Selected as Interactors of
      HIV-1 Nucleocapsid Negatively Interfere with Viral Genome Packaging and Virus
      Maturation.
AB  - A new generation of artificial proteins, derived from alpha-helicoidal HEAT-like
      repeat protein scaffolds (alphaRep), was previously characterized as an effective
      source of intracellular interfering proteins. In this work, a phage-displayed
      library of alphaRep was screened on a region of HIV-1 Gag polyprotein
      encompassing the C-terminal domain of the capsid, the SP1 linker and the
      nucleocapsid. This region is known to be essential for the late steps of HIV-1
      life cycle, Gag oligomerization, viral genome packaging and the last cleavage
      step of Gag, leading to mature, infectious virions. Two strong alphaRep binders
      were isolated from the screen, alphaRep4E3 (32 kDa; 7 internal repeats) and
      alphaRep9A8 (28 kDa; 6 internal repeats). Their antiviral activity against HIV-1
      was evaluated in VLP-producer cells and in human SupT1 cells challenged with HIV
      1. Both alphaRep4E3 and alphaRep9A8 showed a modest but significant antiviral
      effects in all bioassays and cell systems tested. They did not prevent the
      proviral integration reaction, but negatively interfered with late steps of the
      HIV-1 life cycle: alphaRep4E3 blocked the viral genome packaging, whereas
      alphaRep9A8 altered both virus maturation and genome packaging. Interestingly,
      SupT1 cells stably expressing alphaRep9A8 acquired long-term resistance to HIV-1,
      implying that alphaRep proteins can act as antiviral restriction-like factors.

PMID- 29180784
TI  - Singlet oxygen-mediated selective C-H bond hydroperoxidation of ethereal
      hydrocarbons.
AB  - Singlet O2 is a key reactive oxygen species responsible for photodynamic therapy
      and is generally recognized to be chemically reactive towards C=C double bonds.
      Herein, we report the hydroperoxidation/lactonization of alpha-ethereal C-H bonds
      by singlet O2 (1Deltag) under exceptionally mild conditions, i.e., room
      temperature and ambient pressure, with modest to high yields (38~90%) and
      excellent site selectivity. Singlet O2 has been known for > 90 years, but was
      never reported to be able to react with weakly activated C-H bonds in saturated
      hydrocarbons. Theoretical calculations indicate that singlet O2 directly inserts
      into the alpha-ethereal C-H bond in one step with conservation of steric
      configuration in products. The current discovery of chemical reaction of singlet
      oxygen with weakly activated solvent C-H bonds, in addition to physical
      relaxation pathway, provides an important clue to a 35-year-old unresolved
      mystery regarding huge variations of solvent dependent lifetime of singlet O2.

PMID- 29180783
TI  - Ingestion of artificial sweeteners leads to caloric frustration memory in
      Drosophila.
AB  - Non-caloric artificial sweeteners (NAS) are widely used in modern human food,
      raising the question about their health impact. Here we have asked whether NAS
      consumption is a neutral experience at neural and behavioral level, or if NAS can
      be interpreted and remembered as negative experience. We used behavioral and
      imaging approaches to demonstrate that Drosophila melanogaster learn the non
      caloric property of NAS through post-ingestion process. These results show that
      sweet taste is predictive of an energy value, and its absence leads to the
      formation of what we call Caloric Frustration Memory (CFM) that devalues the NAS
      or its caloric enantiomer. CFM formation involves activity of the associative
      memory brain structure, the mushroom bodies (MBs). In vivo calcium imaging of MB
      input dopaminergic neurons that respond to sugar showed a reduced response to NAS
      after CFM formation. Altogether, these findings demonstrate that NAS are a
      negative experience for the brain.

PMID- 29180785
TI  - Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a
      phenotype mimicking a lysosomal storage disease.
AB  - HSD17B1 is a steroid metabolising enzyme. We have previously generated knockout
      mice that had the entire coding region of Hsd17b1 replaced with lacZ-neo cassette
      (Hsd17b1-LacZ/Neo mice). This resulted in a 90% reduction of HSD17B1 activity,
      associated with severe subfertility in the knockout females. The present study
      indicates that Hsd17b1-LacZ/Neo male mice have a metabolic phenotype, including
      reduced adipose mass, increased lean mass and lipid accumulation in the liver.
      During the characterisation of this metabolic phenotype, it became evident that
      the expression of the Naglu gene, located closely upstream of Hsd17b1, was
      severely reduced in all tissues analysed. Similar results were obtained from
      Hsd17b1-LacZ mice after removing the neo cassette from the locus or by crossing
      the Hsd17b1-LacZ/Neo mice with transgenic mice constitutively expressing human
      HSD17B1. The deficiency of Naglu caused the accumulation of glycosaminoglycans in
      all studied mouse models lacking the Hsd17b1 gene. The metabolic phenotypes of
      the Hsd17b1 knockout mouse models were recapitulated in Naglu knockout mice.
      Based on the data we propose that the Hsd17b1 gene includes a regulatory element
      controlling Naglu expression and the metabolic phenotype in mice lacking the
      Hsd17b1 genomic region is caused by the reduced expression of Naglu rather than
      the lack of Hsd17b1.

PMID- 29180786
TI  - New design model for high efficiency cylindrical diffractive microlenses.
AB  - A new model, i.e., the decreasing thickness model (DTM) is proposed and employed
      for designing the cylindrical diffractive microlenses (CDMs). Focal performances
      of the designed CDMs are theoretically investigated by solving Maxwell's
      equations with the boundary element method. For comparison, the CDMs designed by
      the traditional equal thickness model (ETM) are also studied. Theoretical
      simulations demonstrate that focal performances of the designed CDMs are improved
      a lot via replacing the traditional ETM with the proposed DTM. Concretely, the
      focal efficiency is heightened and the focal spot size is shrunk. Experimental
      measurements verify the theoretical simulations well. Especially, the above
      mentioned improvements become more prominent for the CDM with a higher numerical
      aperture.

PMID- 29180787
TI  - Towards the cell-instructive bactericidal substrate: exploring the combination of
      nanotopographical features and integrin selective synthetic ligands.
AB  - Engineering the interface between biomaterials and tissues is important to
      increase implant lifetime and avoid failures and revision surgeries. Permanent
      devices should enhance attachment and differentiation of stem cells, responsible
      for injured tissue repair, and simultaneously discourage bacterial colonization;
      this represents a major challenge. To take first steps towards such a
      multifunctional surface we propose merging topographical and biochemical cues on
      the surface of a clinically relevant material such as titanium. In detail, our
      strategy combines antibacterial nanotopographical features with integrin
      selective synthetic ligands that can rescue the adhesive capacity of the surfaces
      and instruct mesenchymal stem cell (MSC) response. To this end, a smooth
      substrate and two different high aspect ratio topographies have been produced and
      coated either with an alphavbeta3-selective peptidomimetic, an alpha5beta1
      selective peptidomimetic, or an RGD/PHSRN peptidic molecule. Results showed that
      antibacterial effects of the substrates could be maintained when tested on
      pathogenic Pseudomonas aeruginosa. Further, functionalization increased MSC
      adhesion to the surfaces and the alphavbeta3-selective peptidomimetic-coated
      nanotopographies promoted osteogenesis. Such a dual physicochemical approach to
      achieve multifunctional surfaces represents a first step in the design of novel
      cell-instructive biomaterial surfaces.

PMID- 29180788
TI  - Pseudotrichonympha leei, Pseudotrichonympha lifesoni, and Pseudotrichonympha
      pearti, new species of parabasalian flagellates and the description of a rotating
      subcellular structure.
AB  - Pseudotrichonympha is a large and structurally complex genus of parabasalian
      protists that play a key role in the digestion of lignocellulose in the termite
      hindgut. Like many termite symbionts, it has a conspicuous body plan that makes
      genus-level identification relatively easy, but species-level diversity of
      Pseudotrichonympha is understudied. Molecular surveys have suggested the
      diversity is much greater than the current number of described species, and that
      many "species" described in multiple hosts are in fact different, but gene
      sequences from formally described species remain a rarity. Here we describe three
      new species from Coptotermes and Prorhinotermes hosts, including small subunit
      ribosomal RNA (SSU rRNA) sequences from single cells. Based on host
      identification by morphology and DNA barcoding, as well as the morphology and
      phylogenetic position of each symbiont, all three represent new
      Pseudotrichonympha species: P. leei, P. lifesoni, and P. pearti.
      Pseudotrichonympha leei and P. lifesoni, both from Coptotermes, are closely
      related to other Coptotermes symbionts including the type species, P. hertwigi.
      Pseudotrichonympha pearti is the outlier of the trio, more distantly related to
      P. leei and P. lifesoni than they are to one another, and contains unique
      features, including an unusual rotating intracellular structure of unknown
      function.

PMID- 29180789
TI  - The computations that support simple decision-making: A comparison between the
      diffusion and urgency-gating models.
AB  - We investigate a question relevant to the psychology and neuroscience of
      perceptual decision-making: whether decisions are based on steadily accumulating
      evidence, or only on the most recent evidence. We report an empirical comparison
      between two of the most prominent examples of these theoretical positions, the
      diffusion model and the urgency-gating model, via model-based qualitative and
      quantitative comparisons. Our findings support the predictions of the diffusion
      model over the urgency-gating model, and therefore, the notion that evidence
      accumulates without much decay. Gross qualitative patterns and fine structural
      details of the data are inconsistent with the notion that decisions are based
      only on the most recent evidence. More generally, we discuss some strengths and
      weaknesses of scientific methods that investigate quantitative models by
      distilling the formal models to qualitative predictions.

PMID- 29180791
TI  - Surface modification of layered perovskite Sr2TiO4 for improved CO2
      photoreduction with H2O to CH4.
AB  - Layered perovskite Sr2TiO4 photocatalyst was synthesized by using sol-gel method
      with citric acid. In order to increase the surface area of layered perovskite
      Sr2TiO4, and thus to improve its photocatalytic activity for CO2 reduction, its
      surface was modified via hydrogen treatment or exfoliation. The physical and
      chemical properties of the prepared catalysts were characterized by X-ray
      diffraction, high-resolution transmission electron microscopy, elemental mapping
      analysis, energy-dispersive X-ray spectroscopy, N2 adsorption-desorption, UV-Vis
      spectroscopy, X-ray photoelectron spectroscopy, photoluminescence, and
      electrophoretic light scattering. CO2 photoreduction was performed in a closed
      reactor under 6 W/cm2 UV irradiation. The gaseous products were analyzed using a
      gas chromatograph equipped with flame ionization and thermal conductivity
      detectors. The exfoliated Sr2TiO4 catalyst (E-Sr2TiO4) exhibited a narrow band
      gap, a large surface area, and high dispersion. Owing to these advantageous
      properties, E-Sr2TiO4 photocatalyst showed an excellent catalytic performance for
      CO2 photoreduction reaction. The rate of CH4 production from the photoreduction
      of CO2 with H2O using E-Sr2TiO4 was about 3431.77 MUmol/gcat after 8 h.

PMID- 29180790
TI  - Vanillic acid from Actinidia deliciosa impedes virulence in Serratia marcescens
      by affecting S-layer, flagellin and fatty acid biosynthesis proteins.
AB  - Serratia marcescens is one of the important nosocomial pathogens which rely on
      quorum sensing (QS) to regulate the production of biofilm and several virulence
      factors. Hence, blocking of QS has become a promising approach to quench the
      virulence of S. marcescens. For the first time, QS inhibitory (QSI) and
      antibiofilm potential of Actinidia deliciosa have been explored against S.
      marcescens clinical isolate (CI). A. deliciosa pulp extract significantly
      inhibited the virulence and biofilm production without any deleterious effect on
      the growth. Vanillic acid was identified as an active lead responsible for the
      QSI activity. Addition of vanillic acid to the growth medium significantly
      affected the QS regulated production of biofilm and virulence factors in a
      concentration dependent mode in S. marcescens CI, ATCC 14756 and MG1. Furthermore
      vanillic acid increased the survival of Caenorhabditis elegans upon S. marcescens
      infection. Proteomic analysis and mass spectrometric identification of
      differentially expressed proteins revealed the ability of vanillic acid to
      modulate the expression of proteins involved in S-layers, histidine, flagellin
      and fatty acid production. QSI potential of the vanillic acid observed in the
      current study paves the way for exploring it as a potential therapeutic candidate
      to treat S. marcescens infections.

PMID- 29180792
TI  - Twitter-derived neighborhood characteristics associated with obesity and
      diabetes.
AB  - Neighborhood characteristics are increasingly connected with health outcomes.
      Social processes affect health through the maintenance of social norms,
      stimulation of new interests, and dispersal of knowledge. We created zip code
      level indicators of happiness, food, and physical activity culture from
      geolocated Twitter data to examine the relationship between these neighborhood
      characteristics and obesity and diabetes diagnoses (Type 1 and Type 2). We
      collected 422,094 tweets sent from Utah between April 2015 and March 2016. We
      leveraged administrative and clinical records on 1.86 million individuals aged 20
      years and older in Utah in 2015. Individuals living in zip codes with the
      greatest percentage of happy and physically-active tweets had lower obesity
      prevalence-accounting for individual age, sex, nonwhite race, Hispanic ethnicity,
      education, and marital status, as well as zip code population characteristics.
      More happy tweets and lower caloric density of food tweets in a zip code were
      associated with lower individual prevalence of diabetes. Results were robust in
      sibling random effects models that account for family background characteristics
      shared between siblings. Findings suggest the possible influence of sociocultural
      factors on individual health. The study demonstrates the utility and cost
      effectiveness of utilizing existing big data sources to conduct population health
      studies.

PMID- 29180793
TI  - Activation of the mitochondrial unfolded protein response promotes longevity and
      dopamine neuron survival in Parkinson's disease models.
AB  - While the pathogenesis of Parkinson's disease (PD) is incompletely understood,
      mitochondrial dysfunction is thought to play a crucial role in disease
      pathogenesis. Here, we examined the relationship between mitochondrial function
      and dopamine neuron dysfunction and death using C. elegans mutants for three
      mitochondria-related genes implicated in monogenic PD (pdr-1/PRKN, pink-1/PINK1
      and djr-1.1/DJ-1). We found that pdr-1 and pink-1 mutants exhibit deficits in
      dopamine-dependent behaviors, but no loss of dopamine neurons, while djr-1.1
      mutants showed an increased sensitivity to oxidative stress. In examining
      mitochondrial morphology and function, we found that djr-1.1 mutants exhibit
      increased mitochondrial fragmentation leading to decreased rate of oxidative
      phosphorylation and ATP levels. pdr-1 and pink-1 mutants show an accumulation of
      dysfunctional mitochondria with age, which leads to activation of the
      mitochondrial unfolded protein response (mitoUPR). Preventing the upregulation of
      the mitoUPR with a deletion in atfs-1 results in decreased lifespan and dopamine
      neuronal loss in pdr-1 and pink-1 mutants but not in wild-type worms. Overall,
      our results suggest that mutations in pdr-1 and pink-1 cause the accumulation of
      dysfunctional mitochondria, which activates the mitoUPR to mitigate the
      detrimental effect of these mutations on dopamine neuron survival.

PMID- 29180794
TI  - Water Soluble Self-Aggregates Induced Green Emission of Biocompatible Citric Acid
      PEG Hyper Branched Polymer.
AB  - An aliphatic citric acid-PEG hyper-branched polymer (CPHP) with a pi-bond on the
      polymer backbone was synthesized by a single- step melt reaction in which the
      polymerization and pi-bond formation occur simultaneously. The chemical structure
      of CPHP was confirmed by FTIR, 1H-NMR, 13C-NMR and MALDI-TOF mass spectral
      analyses. Aggregates are generally found to disperse in any solvent but the CPHP
      aggregates were soluble in water due to their hybrid nature. The pi-bond in the
      aconitate unit induces green emission by CH/pi interaction while the PEG unit of
      CPHP increases its solubility in water. The soluble aggregates induced green
      emission (SAIE) of the CPHP was investigated by UV-Visible absorption and
      emission spectra, time- correlated single photon counting (TCSPC) and zeta
      potential measurements. The fluorescence life time (tauf) increased from 4.93
      to11.38 ns with an increase in CPHP concentration. The fluorescence quantum yield
      (Phif) of CPHP can be altered by varying the concentration of CPHP.

PMID- 29180795
TI  - Hypertension and obesity comorbidities increases coronary risk, affects domains
      of sexual function and sexual quality of life.
AB  - About 25% of the world's adult population suffers from arterial hypertension with
      about 1.5 billion estimated to develop hypertension by 2025. Hypertensive
      patients have been reported to have a higher risk of developing diabetes and
      sexual dysfunction. Hypertension have been linked with lubricative and orgasmic
      difficulties in females, as wel as ED and vascular disease in men. Obesity has
      also been linked to ED in diabetic males as well as several aspects of female
      sexuality. Hypertension and obesity are closely related, each occurring in
      greater frequency with the other, it is only logical to think that comorbidities
      of obesity and hypertension could increase the risk of cardiovascular disease and
      SD. This research looks at the relationship between hypertension and obesity
      comorbidities and its association with sexual function in type II diabetics.
      Diabetic patients who were at least 18 years old and were engaged in a stable
      heterosexual relationships for at least 1 year were recruited for this study.
      Participants were categorized into the -HYP/-OB, +HYP/-OB and the +HYP/+OB
      groups. Sexual function was assessed using the GRISS-M and GRIS-F for the
      diabetic males and females respectively. Early morning fasting blood samples was
      used in lipid profile as well as FBG assay. The Coronary risk was estimated as
      Total/HDL Cholesterol. Triglyceride levels and coronary risk were highest in the
      +HYP/+OBES group, followed by the +HYP/-OBES group, with the -HYP/-OBES group
      recording the lowest levels. PE and infrequency recorded the highest score among
      the +HYP/+OBES group with the +HYP/-OBES group recording the lowest scores. SQoL
      was highest amongst the -HYP/-OBES group, with the +HYP/+OBES group recording the
      lowest scores. Anorgasmia and avoidance increased along the shades of HYP/OBES
      groups. Comorbidities of hypertension and obesity increases the risk of coronary
      disease, affects some domains of sexual function and decreases the SQoL of
      diabetics.

PMID- 29180796
TI  - Sexual dysfunction as a determinant of cardiovascular outcome in patients
      undergoing chronic hemodialysis.
AB  - Sexual dysfunction (SD) is common in men and women with chronic kidney disease
      (CKD) and is considered as an early marker for cardiovascular (CV) disease. We
      hypothesized that patients with SD have higher risk for vascular damage of the
      large arteries, accelerated vascular aging, and consequently higher CV mortality
      than other end-stage renal disease (ESRD) patients. In this study, the
      International Index of Erectile Function (IIEF) questionnaire and the Female
      Sexual Function Index (FSFI) questionnaire were applied in men and women,
      respectively. Ambulatory blood pressure monitoring (ABPM), arterial stiffness,
      and ankle-brachial index (ABI) were performed in all patients. Pulse wave
      velocity (PWV) was significantly slower in non-SD patients (10.5 vs. 8.8 m/s; p <
      0.001) with significantly lower number of non-SD patients with PWV > 10 m/s
      compared to SD patients (p < 0.001). Only 57% of the patients with prior CV event
      had PWV > 10 m/s. No difference in AIx was observed. Non-SD patients had better
      values of ABI (0.83 vs. 1.09; p < 0.05) with significantly lower number of non-SD
      patients with ABI < 0.9 compared to SD patients (p = 0.001) as well as smaller
      percentage of LVH (57.5% vs. 80.7%; p = 0.01). There were no differences in
      hemodynamic parameters when patients with SD were divided by sex. Pulse wave
      velocity was the strongest predictor of lower IIEF and FSFI scores. Mean survival
      time was longer in non-SD patients than in SD patients (11.6 vs. 10.5 months, p =
      0.019). The higher incidence of prior CV events and CV mortality found in SD
      patients on hemodialysis (HD) is a consequence of accelerated vascular aging.
      Sexual dysfunction in HD patients should also be considered a marker of
      subclinical organ damage and future CV events. Our study confirms the predictive
      role of PWV in HD patients.

PMID- 29180797
TI  - Outcomes of variation in technique and variation in accuracy of measurement in
      penile length measurement.
AB  - Accurate data regarding the size of the erect penis is of great importance to
      several disciplines working with male patients, but little data exists on the
      best technique to measure penile length. While some previous small studies have
      suggested good correlation between stretched penile length, others have shown
      significant variability. Penile girth has been less well studied, and little data
      exist on the possible errors induced by differing observers and different
      techniques. Much of the published data report penile length measured from the
      penopubic skin junction-to-glans tip (STT) rather than pubic bone-to-tip (BTT).
      We wished to assess the accuracy of different techniques of penile measurements
      with multiple observers. Men who achieved full erection using dynamic penile
      Doppler ultrasound for the diagnosis of sexual dysfunction or a desire for
      objective penile measurement were included in the study. Exclusion criteria were
      penile scarring, curvature, or congenital abnormality. In each case, the penis
      was measured by one of the seven andrology specialists in a private air
      conditioned (21  degrees C) environment. Each patient had three parameters
      measured: circumference (girth) of the penile shaft, length from suprapubic skin
      to-distal glans (STT), and pubis-to-distal glans (BTT). The three measurements
      were recorded in the stretched flaccid state, and the same three measurements
      were then repeated in the fully erect state, following induction of full erection
      with intracavernosal injection. We analyzed the accuracy of each flaccid
      measurement using the erect measurements as a reference, for the overall patient
      population and for each observer. In total, 201 adult men (mean age 49.4 years)
      were included in this study. Assessing the penis in the stretched and flaccid
      state gave a mean underestimate of the erect measurement of ~20% (STT length
      23.39%, BTT length 19.86%, and circumference 21.38%). In this large, multicenter,
      multi-observer study of penis size, flaccid measurements were only moderately
      accurate in predicting erect size. They were also significantly observer
      dependent. Measuring penile length from pubic bone to tip of glans is more
      accurate and reliable, the discrepancy being most notable in overweight patients.

PMID- 29180798
TI  - Anthropometric study of penile length in self-declared Brazilians regarding the
      color of the skin as white or black: The study of a Myth.
AB  - This is an observational transversal cohort study in which we aim to analyze the
      Brazilian penis length and compare the penis size of the men self-declared as
      white (SDW) or black (SDB) skin color. Subjects were asked for self-declare
      according to their skin color, after that they have been invited to participate
      in a semi-structured interview so as to have their perception evaluated regarding
      their penis size and their self-esteem as well. Eventually, their penis length
      was measured with an anthropometric ruler. The men's mean penis length who
      declared themselves as black skin color was 16.5 +/- 1.7 cm (penis length in real
      fully-stretched flaccid length) and the men's mean penis length who declared
      themselves as white skin color was 15.8 +/- 1.6 cm (p < 0.001).The majority of
      either SDB (94.0%) or SDW (89.4%) are satisfied with their penis size (p =
      0.464). We have shown that the man's mean penis length who identifies himself as
      black is just a little bit bigger than the one who identifies himself as white.
      However, there were no significant difference between groups regarding self
      assessment of genital body image.

PMID- 29180799
TI  - Low-intensity extracorporeal shock wave therapy for erectile dysfunction after
      radical prostatectomy: a review of preclinical studies.
AB  - Low-intensity extracorporeal shock wave therapy (LI-ESWT) is a novel treatment
      for erectile dysfunction (ED). Its ability to improve erectile function has been
      shown in patients with vasculogenic ED by many randomized-controlled trials
      against sham procedures. However, the role of LI-ESWT in ED caused by radical
      prostatectomy (RP) is still questionable because this type of ED was excluded
      from nearly all clinical studies; it has been investigated in only a few small
      single-arm trials. This review summarizes preclinical studies on mechanisms of
      action of LI-ESWT for ED and neurological diseases to explore the potential of
      this treatment for nerve-impaired ED after RP.

PMID- 29180800
TI  - Electronic Health Record Driven Prediction for Gestational Diabetes Mellitus in
      Early Pregnancy.
AB  - Gestational diabetes mellitus (GDM) is conventionally confirmed with oral glucose
      tolerance test (OGTT) in 24 to 28 weeks of gestation, but it is still uncertain
      whether it can be predicted with secondary use of electronic health records
      (EHRs) in early pregnancy. To this purpose, the cost-sensitive hybrid model
      (CSHM) and five conventional machine learning methods are used to construct the
      predictive models, capturing the future risks of GDM in the temporally aggregated
      EHRs. The experimental data sources from a nested case-control study cohort,
      containing 33,935 gestational women in West China Second Hospital. After data
      cleaning, 4,378 cases and 50 attributes are stored and collected for the data
      set. Through selecting the most feasible method, the cost parameter of CSHM is
      adapted to deal with imbalance of the dataset. In the experiment, 3940 samples
      are used for training and the rest 438 samples for testing. Although the accuracy
      of positive samples is barely acceptable (62.16%), the results suggest that the
      vast majority (98.4%) of those predicted positive instances are real positives.
      To our knowledge, this is the first study to apply machine learning models with
      EHRs to predict GDM, which will facilitate personalized medicine in maternal
      health management in the future.

PMID- 29180801
TI  - Modification and functional adaptation of the MBF1 gene family in the lichenized
      fungus Endocarpon pusillum under environmental stress.
AB  - The multiprotein-bridging factor 1 (MBF1) gene family is well known in archaea,
      non-lichenized fungi, plants, and animals, and contains stress tolerance-related
      genes. Here, we identified four unique mbf1 genes in the lichenized fungi
      Endocarpon spp. A phylogenetic analysis based on protein sequences showed the
      translated MBF1 proteins of the newly isolated mbf1 genes formed a monophyletic
      clade different from other lichen-forming fungi and Ascomycota groups in general,
      which may reflect the evolution of the biological functions of MBF1s. In contrast
      to the lack of function reported in yeast, we determined that lysine114 in the
      deduced Endocarpon pusillum MBF1 protein (EpMBF1) had a specific function that
      was triggered by environmental stress. Further, the Endocarpon-specific C
      terminus of EpMBF1 was found to participate in stress tolerance. Epmbf1 was
      induced by a number of abiotic stresses in E. pusillum and transgenic yeast, and
      its stress-resistant ability was stronger than that of the yeast mbf1. These
      findings highlight the evolution and function of EpMBF1 and provide new insights
      into the co-evolution hypothesis of MBF1 and TATA-box-binding proteins.

PMID- 29180802
TI  - Two heart failure phenotypes in arterial hypertension: a clinical study.

PMID- 29180803
TI  - Prevalence and correlates of hypertension in a semi-rural population of Southern
      India.
AB  - While elevated blood pressure is a recognized risk factor for cardiovascular
      disease, the prevalence of hypertension still remains unclear for most
      populations. A door-to-door survey was conducted using modified WHO STEPS
      questionnaire in a group of villages under the Thavanampalle Mandal of Chittoor
      District in the state of Andhra Pradesh of South India. Data were collated and
      analyzed for 16,636 individuals (62.3% females and 37.7% males) above 15 years of
      age. Overall, prevalence of hypertension (as per JNC-7 classification) was found
      to be 27.0% (95% CI, 26.3, 27.7) in the surveyed community with 56.7% of the
      total hypertensives being diagnosed for the first time during the survey. An
      additional 39.1% had their blood pressure readings in the prehypertensive range.
      Among the known Hypertensives on treatment only 46.2% had a blood pressure
      recording within acceptable limits, with 31.2% in the prehypertensive range and
      only 15.0% in the normal range. Systolic blood pressure (SBP) of the surveyed
      population showed a continuous linear increase with age, but diastolic blood
      pressure (DBP) peaked and started reducing in early fifth decade in males. Male
      gender, increasing age, higher body mass index (BMI), increased waist-hip ratio,
      increased body weight, family history of hypertension, death of spouse, and
      diabetes were found to be positively correlated with hypertension. Risk factors
      of alcohol intake, use of ground nut/palm oil, and family history of diabetes
      lost their independent predictive ability for hypertension on multivariate
      logistic regression analysis. The level of physical activity was also not found
      to be a significant predictor of hypertension in the study population.

PMID- 29180804
TI  - Hypertension prevalence, awareness, treatment, and control in northeast China: a
      population-based cross-sectional survey.
AB  - Hypertension has been recognized as a major risk factor for cardiovascular
      disease. We aimed to analyze the current prevalence, awareness, treatment, and
      control of hypertension in northeast China. This cross-sectional survey adopted
      the multistage stratified random cluster sampling method to obtain a
      representative sample of adults aged 40 years or older in the general population
      of northeast China. Hypertension was defined as a systolic blood pressure (SBP)
      >= 140 mm Hg, or diastolic blood pressure (DBP) >= 90 mm Hg, or self-reported use
      of antihypertensive medications in the last 2 weeks irrespective of BP.
      Altogether 4052 participants were included with weighted prevalence of
      hypertension of 57.3%. Among them, 47.4% were aware of their condition; 78.8%
      took antihypertensive medication, but only 10.2% had their blood pressure
      controlled. Individuals who were overweight/obesity, with dyslipidemia, or
      diabetes were at a higher risk of hypertension; these people also more likely to
      be aware of their condition. Subjects with a personal history of stroke were more
      inclined to receive antihypertensive medication, but that did not necessarily
      translate to well-controlled hypertension. Moreover, dyslipidemia (OR = 0.600;
      95% CI: 0.375, 0.960) were associated with poor hypertension control. Subjects
      using combination of antihypertensive medications (OR = 2.924; 95% CI: 1.606,
      5.325) or with a family history of coronary heart disease were more likely to
      have their blood pressure controlled. Our study identified a high prevalence of
      hypertension in northeast China. Although awareness and treatment rates improved
      over the last decade, the control rate remained disproportionately and
      unacceptably low.

PMID- 29180805
TI  - A fast approach to detect gene-gene synergy.
AB  - Selecting informative genes, including individually discriminant genes and
      synergic genes, from expression data has been useful for medical diagnosis and
      prognosis. Detecting synergic genes is more difficult than selecting individually
      discriminant genes. Several efforts have recently been made to detect gene-gene
      synergies, such as dendrogram-based I(X 1; X 2; Y) (mutual information), doublets
      (gene pairs) and MIC(X 1; X 2; Y) based on the maximal information coefficient.
      It is unclear whether dendrogram-based I(X 1; X 2; Y) and doublets can capture
      synergies efficiently. Although MIC(X 1; X 2; Y) can capture a wide range of
      interaction, it has a high computational cost triggered by its 3-D search. In
      this paper, we developed a simple and fast approach based on abs conversion type
      (i.e. Z = |X 1 - X 2|) and t-test, to detect interactions in simulation and real
      world datasets. Our results showed that dendrogram-based I(X 1; X 2; Y) and
      doublets are helpless for discovering pair-wise gene interactions, our approach
      can discover typical pair-wise synergic genes efficiently. These synergic genes
      can reach comparable accuracy to the individually discriminant genes using the
      same number of genes. Classifier cannot learn well if synergic genes have not
      been converted properly. Combining individually discriminant and synergic genes
      can improve the prediction performance.

PMID- 29180806
TI  - Rational design of cholesterol oxidase for efficient bioresolution of cholestane
      skeleton substrates.
AB  - Cholesterol oxidase catalyzes the oxidation and isomerization of the cholestane
      substrates leading to the addition of a hydroxyl group at the C3 position.
      Rational engineering of the cholesterol oxidase from Pimelobacter simplex (PsChO)
      was performed. Mutagenesis of V64 and F70 improved the catalytic activities
      toward cholestane substrates. Molecular dynamics simulations, together with
      structure-activity relationship analysis, revealed that both V64C and F70V
      increased the binding free energy between PsChO mutants and cholesterol. F70V and
      V64C mutations might cause the movement of loops L56-P77, K45-P49 and L350-E354
      at active site. They enlarged the substrate-binding cavity and relieved the
      steric interference with substrates facilitating recognition of C17 hydrophobic
      substrates with long side chain substrates.

PMID- 29180807
TI  - Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated
      immunity.
AB  - The sensor RIG-I detects double-stranded RNA derived from RNA viruses. Although
      RIG-I is also known to have a role in the antiviral response to DNA viruses,
      physiological RNA species recognized by RIG-I during infection with a DNA virus
      are largely unknown. Using next-generation RNA sequencing (RNAseq), we found that
      host-derived RNAs, most prominently 5S ribosomal RNA pseudogene 141 (RNA5SP141),
      bound to RIG-I during infection with herpes simplex virus 1 (HSV-1). Infection
      with HSV-1 induced relocalization of RNA5SP141 from the nucleus to the cytoplasm,
      and virus-induced shutoff of host protein synthesis downregulated the abundance
      of RNA5SP141-interacting proteins, which allowed RNA5SP141 to bind RIG-I and
      induce the expression of type I interferons. Silencing of RNA5SP141 strongly
      dampened the antiviral response to HSV-1 and the related virus Epstein-Barr virus
      (EBV), as well as influenza A virus (IAV). Our findings reveal that antiviral
      immunity can be triggered by host RNAs that are unshielded following depletion of
      their respective binding proteins by the virus.

PMID- 29180810
TI  - Food regimes and the geopolitics of wheat.

PMID- 29180808
TI  - Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses
      macrophages and is a target of cancer immunotherapy.
AB  - Exciting progress in the field of cancer immunotherapy has renewed the urgency of
      the need for basic studies of immunoregulation in both adaptive cell lineages and
      innate cell lineages. Here we found a central role for major histocompatibility
      complex (MHC) class I in controlling the phagocytic function of macrophages. Our
      results demonstrated that expression of the common MHC class I component beta2
      microglobulin (beta2M) by cancer cells directly protected them from phagocytosis.
      We further showed that this protection was mediated by the inhibitory receptor
      LILRB1, whose expression was upregulated on the surface of macrophages, including
      tumor-associated macrophages. Disruption of either MHC class I or LILRB1
      potentiated phagocytosis of tumor cells both in vitro and in vivo, which defines
      the MHC class I-LILRB1 signaling axis as an important regulator of the effector
      function of innate immune cells, a potential biomarker for therapeutic response
      to agents directed against the signal-regulatory protein CD47 and a potential
      target of anti-cancer immunotherapy.

PMID- 29180809
TI  - Structural basis for TNA synthesis by an engineered TNA polymerase.
AB  - Darwinian evolution experiments carried out on xeno-nucleic acid (XNA) polymers
      require engineered polymerases that can faithfully and efficiently copy genetic
      information back and forth between DNA and XNA. However, current XNA polymerases
      function with inferior activity relative to their natural counterparts. Here, we
      report five X-ray crystal structures that illustrate the pathway by which alpha
      (L)-threofuranosyl nucleic acid (TNA) triphosphates are selected and extended in
      a template-dependent manner using a laboratory-evolved polymerase known as Kod
      RI. Structural comparison of the apo, binary, open and closed ternary, and
      translocated product detail an ensemble of interactions and conformational
      changes required to promote TNA synthesis. Close inspection of the active site in
      the closed ternary structure reveals a sub-optimal binding geometry that explains
      the slow rate of catalysis. This key piece of information, which is missing for
      all naturally occurring archaeal DNA polymerases, provides a framework for
      engineering new TNA polymerase variants.

PMID- 29180811
TI  - Loopholes for smuggling DNA into pollen.

PMID- 29180812
TI  - Raising the BAR of specificity.

PMID- 29180813
TI  - Pollen magnetofection for genetic modification with magnetic nanoparticles as
      gene carriers.
AB  - Genetic modification plays a vital role in breeding new crops with excellent
      traits. Almost all the current genetic modification methods require regeneration
      from tissue culture, involving complicated, long and laborious processes. In
      particular, many crop species such as cotton are difficult to regenerate. Here,
      we report a novel transformation platform technology, pollen magnetofection, to
      directly produce transgenic seeds without regeneration. In this system, exogenous
      DNA loaded with magnetic nanoparticles was delivered into pollen in the presence
      of a magnetic field. Through pollination with magnetofected pollen, transgenic
      plants were successfully generated from transformed seeds. Exogenous DNA was
      successfully integrated into the genome, effectively expressed and stably
      inherited in the offspring. Our system is culture-free and genotype independent.
      In addition, it is simple, fast and capable of multi-gene transformation. We
      envision that pollen magnetofection can transform almost all crops, greatly
      facilitating breeding processes of new varieties of transgenic crops.

PMID- 29180814
TI  - The crystal structure of Deg9 reveals a novel octameric-type HtrA protease.
AB  - The high temperature requirement A (HtrA) proteases (also termed Deg proteases)
      play important roles in diverse organisms by regulating protein quality and
      quantity. One of the 16 Arabidopsis homologs, Deg9, is located in the nucleus
      where it modulates cytokinin- and light-mediated signalling via degrading the
      ARABIDOPSIS RESPONSE REGULATOR 4 (ARR4). To uncover the structural features
      underlying the proteolytic activity of Deg9, we determined its crystal structure.
      Unlike the well-established trimeric building block of HtrAs, Deg9 displays a
      novel octameric structure consisting of two tetrameric rings that have distinct
      conformations. Based on the structural architecture, we generated several mutant
      variants of Deg9, determined their structure and tested their proteolytic
      activity towards ARR4. The results of the structural and biochemical analyses
      allowed us to propose a model for a novel mechanism of substrate recognition and
      activity regulation of Deg9. In this model, protease activation of one tetramer
      is mediated by en-bloc reorientation of the protease domains to open an entrance
      for the substrate in the opposite (inactive) tetramer. This study provides the
      structural basis for understanding how the levels of nuclear signal components
      are regulated by a plant protease.

PMID- 29180815
TI  - Non-specific activities of the major herbicide-resistance gene BAR.
AB  - Bialaphos resistance (BAR) and phosphinothricin acetyltransferase (PAT) genes,
      which convey resistance to the broad-spectrum herbicide phosphinothricin (also
      known as glufosinate) via N-acetylation, have been globally used in basic plant
      research and genetically engineered crops 1-4 . Although early in vitro enzyme
      assays showed that recombinant BAR and PAT exhibit substrate preference toward
      phosphinothricin over the 20 proteinogenic amino acids 1 , indirect effects of
      BAR-containing transgenes in planta, including modified amino acid levels, have
      been seen but without the identification of their direct causes 5,6 . Combining
      metabolomics, plant genetics and biochemical approaches, we show that transgenic
      BAR indeed converts two plant endogenous amino acids, aminoadipate and
      tryptophan, to their respective N-acetylated products in several plant species.
      We report the crystal structures of BAR, and further delineate structural basis
      for its substrate selectivity and catalytic mechanism. Through structure-guided
      protein engineering, we generated several BAR variants that display significantly
      reduced non-specific activities compared with its wild-type counterpart in vivo.
      The transgenic expression of enzymes can result in unintended off-target
      metabolism arising from enzyme promiscuity. Understanding such phenomena at the
      mechanistic level can facilitate the design of maximally insulated systems
      featuring heterologously expressed enzymes.

PMID- 29180817
TI  - Virus replicon particle vaccines expressing nucleoprotein of influenza A virus
      mediate enhanced inflammatory responses in pigs.
AB  - Studies in the mouse model indicate that the nucleoprotein of influenza A virus
      represents an interesting vaccine antigen being well conserved across subtypes of
      influenza virus but still able to induce protective immune responses. Here we
      show that immunizations of pigs with vesicular stomatitis virus- and classical
      swine fever virus-derived replicon (VRP) particles expressing the nucleoprotein
      (NP) of H1N1 A/swine/Belzig/2/01 induced potent antibody and T-cell responses
      against influenza A virus. In contrast to a conventional whole inactivated virus
      vaccine, the VRP vaccines induced both NP-specific CD4 and CD8 T cells responses,
      including interferon-gamma and tumor-necrosis-factor dual-secreting cell.
      Although T-cells and antibody responses were cross-reactive with the heterologous
      H1N2 A/swine/Bakum/R757/2010 challenge virus, they did not provide protection
      against infection. Surprisingly, vaccinated pigs showed enhanced virus shedding,
      lung inflammation and increased levels of systemic and lung interferon-alpha as
      well as elevated lung interleukin-6. In conclusion, our study shows that NP,
      although efficacious in the mouse model, appears not to be a promising stand
      alone vaccine antigen for pigs.

PMID- 29180818
TI  - OCT4 supports extended LIF-independent self-renewal and maintenance of
      transcriptional and epigenetic networks in embryonic stem cells.
AB  - Embryonic stem (ES) cell pluripotency is governed by OCT4-centric transcriptional
      networks. Conventional ES cells can be derived and maintained in vitro with media
      containing the cytokine leukemia inhibitory factor (LIF), which propagates the
      pluripotent state by activating STAT3 signaling, and simultaneous inhibition of
      glycogen synthase kinase-3 (GSK3) and MAP kinase/ERK kinase signaling. However,
      it is unclear whether overexpression of OCT4 is sufficient to overcome LIF
      dependence. Here, we show that inducible expression of OCT4 (iOCT4) supports long
      term LIF-independent self-renewal of ES cells cultured in media containing fetal
      bovine serum (FBS) and a glycogen synthase kinase-3 (GSK3) inhibitor, and in
      serum-free media. Global expression analysis revealed that LIF-independent iOCT4
      ES cells and control ES cells exhibit similar transcriptional programs relative
      to epiblast stem cells (EpiSCs) and differentiated cells. Epigenomic profiling
      also demonstrated similar patterns of histone modifications between LIF
      independent iOCT4 and control ES cells. Moreover, LIF-independent iOCT4 ES cells
      retain the capacity to differentiate in vitro and in vivo upon downregulation of
      OCT4 expression. These findings indicate that OCT4 expression is sufficient to
      sustain intrinsic signaling in a LIF-independent manner to promote ES cell
      pluripotency and self-renewal.

PMID- 29180819
TI  - Quantum-disordered state of magnetic and electric dipoles in an organic Mott
      system.
AB  - Strongly enhanced quantum fluctuations often lead to a rich variety of quantum
      disordered states. Developing approaches to enhance quantum fluctuations may open
      paths to realize even more fascinating quantum states. Here, we demonstrate that
      a coupling of localized spins with the zero-point motion of hydrogen atoms, that
      is, proton fluctuations in a hydrogen-bonded organic Mott insulator provides a
      different class of quantum spin liquids (QSLs). We find that divergent dielectric
      behavior associated with the approach to hydrogen-bond order is suppressed by the
      quantum proton fluctuations, resulting in a quantum paraelectric (QPE) state.
      Furthermore, our thermal-transport measurements reveal that a QSL state with
      gapless spin excitations rapidly emerges upon entering the QPE state. These
      findings indicate that the quantum proton fluctuations give rise to a QSL-a
      quantum-disordered state of magnetic and electric dipoles-through the coupling
      between the electron and proton degrees of freedom.

PMID- 29180820
TI  - Subcutaneous white adipocytes express a light sensitive signaling pathway
      mediated via a melanopsin/TRPC channel axis.
AB  - Subcutaneous white adipose tissue (scWAT) is the major fat depot in humans and is
      a central player in regulating whole body metabolism. Skin exposure to UV
      wavelengths from sunlight is required for Vitamin D synthesis and pigmentation,
      although it is plausible that longer visible wavelengths that penetrate the skin
      may regulate scWAT function. In this regard, we discovered a novel blue light
      sensitive current in human scWAT that is mediated by melanopsin coupled to
      transient receptor potential canonical cation channels. This pathway is activated
      at physiological intensities of light that penetrate the skin on a sunny day.
      Daily exposure of differentiated adipocytes to blue light resulted in decreased
      lipid droplet size, increased basal lipolytic rate and alterations in adiponectin
      and leptin secretion. Our results suggest that scWAT function may be directly
      under the influence of ambient sunlight exposure and may have important
      implications for our current understanding of adipocyte biology. (150 words).

PMID- 29180821
TI  - Specific Features of SVZ Neurogenesis After Cortical Ischemia: a Longitudinal
      Study.
AB  - Stroke is a devastating disease with an increasing prevalence. Part of the
      current development in stroke therapy is focused in the chronic phase, where
      neurorepair mechanisms such as neurogenesis, are involved. In the adult brain,
      one of the regions where neurogenesis takes place is the subventricular zone
      (SVZ) of the lateral ventricles. Given the possibility to develop pharmacological
      therapies to stimulate this process, we have performed a longitudinal analysis of
      neurogenesis in a model of cortical ischemia in mice. Our results show an initial
      decrease of SVZ proliferation at 24 h, followed by a recovery leading to an
      increase at 14d and a second decrease 28d after stroke. Coinciding with the 24 h
      proliferation decrease, an increase in the eutopic neuroblast migration towards
      the olfactory bulb was observed. The analysis of the neuroblast ectopic migration
      from the SVZ toward the lesion showed an increase in this process from day 14
      after the insult. Finally, our data revealed an increased number of new cortical
      neurons in the peri-infarct cortex 65d after the insult. In summary, we report
      here critical check-points about post-stroke neurogenesis after cortical
      infarcts, important for the pharmacological modulation of this process in stroke
      patients.

PMID- 29180822
TI  - Damage-induced lncRNAs control the DNA damage response through interaction with
      DDRNAs at individual double-strand breaks.
AB  - The DNA damage response (DDR) preserves genomic integrity. Small non-coding RNAs
      termed DDRNAs are generated at DNA double-strand breaks (DSBs) and are critical
      for DDR activation. Here we show that active DDRNAs specifically localize to
      their damaged homologous genomic sites in a transcription-dependent manner.
      Following DNA damage, RNA polymerase II (RNAPII) binds to the MRE11-RAD50-NBS1
      complex, is recruited to DSBs and synthesizes damage-induced long non-coding RNAs
      (dilncRNAs) from and towards DNA ends. DilncRNAs act both as DDRNA precursors and
      by recruiting DDRNAs through RNA-RNA pairing. Together, dilncRNAs and DDRNAs fuel
      DDR focus formation and associate with 53BP1. Accordingly, inhibition of RNAPII
      prevents DDRNA recruitment, DDR activation and DNA repair. Antisense
      oligonucleotides matching dilncRNAs and DDRNAs impair site-specific DDR focus
      formation and DNA repair. We propose that DDR signalling sites, in addition to
      sharing a common pool of proteins, individually host a unique set of site
      specific RNAs necessary for DDR activation.

PMID- 29180823
TI  - HUWE1 variants cause dominant X-linked intellectual disability: a clinical study
      of 21 patients.
AB  - Whole-gene duplications and missense variants in the HUWE1 gene (NM_031407.6)
      have been reported in association with intellectual disability (ID). Increased
      gene dosage has been observed in males with non-syndromic mild to moderate ID
      with speech delay. Missense variants reported previously appear to be associated
      with severe ID in males and mild or no ID in obligate carrier females. Here, we
      report the largest cohort of patients with HUWE1 variants, consisting of 14
      females and 7 males, with 15 different missense variants and one splice site
      variant. Clinical assessment identified common clinical features consisting of
      moderate to profound ID, delayed or absent speech, short stature with small hands
      and feet and facial dysmorphism consisting of a broad nasal tip, deep set eyes,
      epicanthic folds, short palpebral fissures, and a short philtrum. We describe for
      the first time that females can be severely affected, despite preferential
      inactivation of the affected X chromosome. Three females with the c.329 G  >  A
      p.Arg110Gln variant, present with a phenotype of mild ID, specific facial
      features, scoliosis and craniosynostosis, as reported previously in a single
      patient. In these females, the X inactivation pattern appeared skewed in favour
      of the affected transcript. In summary, HUWE1 missense variants may cause
      syndromic ID in both males and females.

PMID- 29180825
TI  - Novel predators emit novel cues: a mechanism for prey naivety towards alien
      predators.
AB  - Detecting enemies is crucial for survival and a trait that develops over an
      evolutionary timeframe. Introduced species disrupt coevolved systems of
      communication and detection in their new ranges, often leading to devastating
      impacts. The classic example is prey naivety towards alien predators, whereby
      prey fail to recognise a new predator. Yet exactly why native prey fail to
      recognise alien predators remains puzzling. Naivety theory predicts that it is
      because novel predators emit novel cues. Distantly related animals have distinct
      evolutionary histories, physiologies and ecologies, predicting they will emit
      different cues. Yet it also possible that all predators emit similar cues because
      they are carnivorous. We investigate whether odour cues differ between placental
      and marsupial carnivores in Australia, where native prey experienced only
      marsupial mammal predation until ~4000 years ago. We compared volatile chemical
      profiles of urine, scats and bedding from four placental and three marsupial
      predators. Chemical profiles showed little overlap between placental and
      marsupial carnivores across all odour types, suggesting that cue novelty is a
      plausible mechanism for prey naivety towards alien predators. Our results also
      suggest a role for olfactory cues to complement visual appearance and
      vocalisations as biologically meaningful ways to differentiate species.

PMID- 29180824
TI  - Genetic Architecture and Candidate Genes Identified for Follicle Number in
      Chicken.
AB  - Follicular development has a major impact on reproductive performance. Most
      previous researchers focused on molecular mechanisms of follicular development.
      The genetic architecture underlying the number of follicle, however, has yet not
      to be thoroughly defined in chicken. Here we report a genome-wide association
      study for the genetic architecture determining the numbers of follicles in a
      large F2 resource population. The results showed heritability were low to
      moderate (0.05-0.28) for number of pre-ovulatory follicles (POF), small yellow
      follicles (SYF) and atresia follicles (AF). The highly significant SNPs
      associated with SYF were mainly located on GGA17 and GGA28. Only four significant
      SNPs were identified for POF on GGA1. The variance partitioned across chromosomes
      and chromosome lengths had a linear relationship for SYF (R2 = 0.58). The
      enriched genes created by the closest correspondent significant SNPs were found
      to be involved in biological pathways related to cell proliferation, cell cycle
      and cell survival. Two promising candidate genes, AMH and RGS3, were suggested to
      be prognostic biomarkers for SYF. In conclusion, this study offers the first
      evidence of genetic variance and positional candidate genes which influence the
      number of SYF in chicken. These identified informative SNPs may facilitate
      selection for an improved reproductive performance of laying hens.

PMID- 29180826
TI  - Persistent inhibition of pore-based cell migration by sub-toxic doses of
      miuraenamide, an actin filament stabilizer.
AB  - Opposed to tubulin-binding agents, actin-binding small molecules have not yet
      become part of clinical tumor treatment, most likely due to the fear of general
      cytotoxicity. Addressing this problem, we investigated the long-term efficacy of
      sub-toxic doses of miuraenamide, an actin filament stabilizing natural compound,
      on tumor cell (SKOV3) migration. No cytotoxic effects or persistent morphological
      changes occurred at a concentration of miuraenamide of 20 nM. After 72 h
      treatment with this concentration, nuclear stiffness was increased, causing
      reduced migration through pores in a Boyden chamber, while cell migration and
      chemotaxis per se were unaltered. A concomitant time-resolved proteomic approach
      showed down regulation of a protein cluster after 56 h treatment. This cluster
      correlated best with the Wnt signaling pathway. A further analysis of the actin
      associated MRTF/SRF signaling showed a surprising reduction of SRF-regulated
      proteins. In contrast to acute effects of actin-binding compounds on actin at
      high concentrations, long-term low-dose treatment elicits much more subtle but
      still functionally relevant changes beyond simple destruction of the
      cytoskeleton. These range from biophysical parameters to regulation of protein
      expression, and may help to better understand the complex biology of actin, as
      well as to initiate alternative regimes for the testing of actin-targeting drugs.

PMID- 29180827
TI  - Development and Validation of High Performance Liquid Chromatographic Method for
      Determination of Gentisic Acid and Related Renal Cell Carcinoma Biomarkers in
      Urine.
AB  - A reversed phase liquid chromatographic (RPLC) method was developed to
      simultaneously detect and quantify creatinine, quinolinic acid, gentisic acid and
      4-hydroxybenzoic acid in urine. These four bio-markers are present in relatively
      high concentrations in urine. Using a 5% methanol in water mobile phase with 0.6%
      acetic acid and a Zorbax C18 column, baseline resolution for all four biomarkers
      in synthetic urine was achieved. Better resolution was obtained for the
      separation of these four compounds when water rich mobile phases were used.
      Detection of the four biomarkers in urine using the proposed RPLC method is
      limited by background from the urine matrix for the later eluting compounds and
      from the dead marker for earlier eluting compounds.

PMID- 29180828
TI  - Plant litter functional diversity effects on litter mass loss depend on the macro
      detritivore community.
AB  - A better understanding of the mechanisms driving litter diversity effects on
      decomposition is needed to predict how biodiversity losses affect this crucial
      ecosystem process. In a microcosm study, we investigated the effects of litter
      functional diversity and two major groups of soil macro-detritivores on the mass
      loss of tree leaf litter mixtures. Furthermore, we tested the effects of litter
      trait community means and dissimilarity on litter mass loss for seven traits
      relevant to decomposition. We expected macro-detritivore effects on litter mass
      loss to be most pronounced in litter mixtures of high functional diversity. We
      used 24 leaf mixtures differing in functional diversity, which were composed of
      litter from four species from a pool of 16 common European tree species.
      Earthworms, isopods, or a combination of both were added to each litter
      combination for two months. Litter mass loss was significantly higher in the
      presence of earthworms than in that of isopods, whereas no synergistic effects of
      macro-detritivore mixtures were found. The effect of functional diversity of the
      litter material was highest in the presence of both macro-detritivore groups,
      supporting the notion that litter diversity effects are most pronounced in the
      presence of different detritivore species. Species-specific litter mass loss was
      explained by nutrient content, secondary compound concentration, and structural
      components. Moreover, dissimilarity in N concentrations increased litter mass
      loss, probably because detritivores having access to nutritionally diverse food
      sources. Furthermore, strong competition between the two macro-detritivores for
      soil surface litter resulted in a decrease of survival of both macro
      detritivores. These results show that the effects of litter functional diversity
      on decomposition are contingent upon the macro-detritivore community and
      composition. We conclude that the temporal dynamics of litter trait diversity
      effects and their interaction with detritivore diversity are key to advancing our
      understanding of litter mass loss in nature.

PMID- 29180829
TI  - Automated detection of geological landforms on Mars using Convolutional Neural
      Networks.
AB  - The large volume of high-resolution images acquired by the Mars Reconnaissance
      Orbiter has opened a new frontier for developing automated approaches to
      detecting landforms on the surface of Mars. However, most landform classifiers
      focus on crater detection, which represents only one of many geological landforms
      of scientific interest. In this work, we use Convolutional Neural Networks
      (ConvNets) to detect both volcanic rootless cones and transverse aeolian ridges.
      Our system, named MarsNet, consists of five networks, each of which is trained to
      detect landforms of different sizes. We compare our detection algorithm with a
      widely used method for image recognition, Support Vector Machines (SVMs) using
      Histogram of Oriented Gradients (HOG) features. We show that ConvNets can detect
      a wide range of landforms and has better accuracy and recall in testing data than
      traditional classifiers based on SVMs.

PMID- 29180831
TI  - Internal conflict, market uniformity, and transparency in price competition
      between teams.
AB  - The way profits are divided within successful teams imposes different degrees of
      internal conflict. We experimentally examine how the level of internal conflict,
      and whether such conflict is transparent to other teams, affects teams' ability
      to compete vis-a-vis each other, and, consequently, market outcomes. Participants
      took part in a repeated Bertrand duopoly game between three-player teams which
      had either the same or different level of internal conflict (uniform vs. mixed).
      Profit division was either private-pay (high conflict; each member received her
      own asking price) or equal-pay (low conflict; profits were divided equally). We
      find that internal conflict leads to (tacit) coordination on high prices in
      uniform private-pay duopolies, but places private-pay teams at a competitive
      disadvantage in mixed duopolies. Competition is softened by transparency in
      uniform markets, but intensified in mixed markets. We propose an explanation of
      the results and discuss implications for managers and policy makers. (D43, L22,
      C92).

PMID- 29180830
TI  - Mycosphaerellaceae - Chaos or clarity?
AB  - The Mycosphaerellaceae represent thousands of fungal species that are associated
      with diseases on a wide range of plant hosts. Understanding and stabilising the
      taxonomy of genera and species of Mycosphaerellaceae is therefore of the utmost
      importance given their impact on agriculture, horticulture and forestry. Based on
      previous molecular studies, several phylogenetic and morphologically distinct
      genera within the Mycosphaerellaceae have been delimited. In this study a
      multigene phylogenetic analysis (LSU, ITS and rpb2) was performed based on 415
      isolates representing 297 taxa and incorporating ex-type strains where available.
      The main aim of this study was to resolve the phylogenetic relationships among
      the genera currently recognised within the family, and to clarify the position of
      the cercosporoid fungi among them. Based on these results many well-known genera
      are shown to be paraphyletic, with several synapomorphic characters that have
      evolved more than once within the family. As a consequence, several old generic
      names including Cercosporidium, Fulvia, Mycovellosiella, Phaeoramularia and
      Raghnildiana are resurrected, and 32 additional genera are described as new.
      Based on phylogenetic data 120 genera are now accepted within the family, but
      many currently accepted cercosporoid genera still remain unresolved pending fresh
      collections and DNA data. The present study provides a phylogenetic framework for
      future taxonomic work within the Mycosphaerellaceae.

PMID- 29180832
TI  - Emotion Language in Trauma Narratives is Associated with Better Psychological
      Adjustment among Survivors of Childhood Sexual Abuse.
AB  - Traumatized individuals are often encouraged to confront their experiences by
      talking or writing about them. However, survivors of childhood sexual abuse (CSA)
      might find it especially difficult to process abuse experiences, particularly
      when the abuse is more severe, which could put them at greater risk for mental
      health problems. The current study examined whether CSA survivors who use emotion
      language when describing their abuse experiences exhibit better mental health. We
      analyzed the trauma narratives of 55 adults who, as children, were part of a
      larger study of the long-term emotional effects of criminal prosecutions on CSA
      survivors. Abuse narratives were analyzed using the Linguistic Inquiry and Word
      Count (LIWC) program. We examined whether positive and negative emotion language
      in participants' abuse narratives were associated with self- and caregiver
      reported mental health symptoms and whether these associations differed according
      to the severity of the abuse. As hypothesized, participants who used more
      positive and negative emotion language had better psychological outcomes,
      especially when the abuse was severe. Our findings suggest that survivors of more
      severe abuse might benefit from including emotion language, whether positive or
      negative in valence, when describing the abuse.

PMID- 29180833
TI  - Growth Differentiation Factor-15 Is a Predictor of Mortality in Critically Ill
      Patients with Sepsis.
AB  - Growth differentiation factor-15 (GDF-15) is a member of the transforming growth
      factor-beta superfamily related to inflammation and macrophage activation. Serum
      concentrations of GDF-15 can predict poor survival in chronic diseases, but its
      role in sepsis is obscure. Therefore, we investigated GDF-15 as a prognostic
      biomarker in critically ill patients. We measured GDF-15 levels in 219 critically
      ill patients (146 with sepsis, 73 without sepsis) upon admission to the intensive
      care unit (ICU), in comparison to 66 healthy controls. GDF-15 levels were
      significantly increased in ICU patients compared to controls. GDF-15 was further
      increased in sepsis and showed a strong association with organ dysfunction
      (kidney, liver and lactate) and disease severity (APACHE II and SOFA score). High
      GDF-15 concentrations at admission independently predicted ICU (HR 3.42; 95% CI
      1.33-8.78) and overall mortality (HR 2.02, 95% CI 1.02-3.88) in all ICU
      critically ill patients as well as in a large subgroup of sepsis patients (ICU
      mortality: HR 3.16; 95% CI 1.10-9.07; overall mortality: HR 2.62; 95% CI 1.14
      6.02). Collectively, serum GDF-15 levels are significantly increased in
      critically ill patients, associated with sepsis, organ failure, and disease
      severity. High GDF-15 levels at ICU admission predict short- and long-term
      mortality risk.

PMID- 29180834
TI  - Increased Levels of S100A8/A9 in Patients with Peritonsillar Abscess: A New
      Promising Diagnostic Marker to Differentiate between Peritonsillar Abscess and
      Peritonsillitis.
AB  - Peritonsillar abscess (PTA) is a very frequent reason for urgent outpatient
      consultation and otolaryngological hospital admission. Early, correct diagnosis
      and therapy of peritonsillar abscess are important to prevent possible life
      threatening complications. Based on physical examinations, a reliable
      differentiation between peritonsillar cellulitis and peritonsillar abscess is
      restricted. A heterodimeric complex called calprotectin consists of the S100
      proteins A8 and A9 (S100A8/A9) and is predominantly expressed not only in
      monocytes and neutrophils but also in epithelial cells. Due to its release by
      activated phagocytes at local sites of inflammation, we assumed S100A8/A9 to be a
      potential biomarker for peritonsillar abscess. We examined serum and saliva of
      patients with peritonsillitis, acute tonsillitis, peritonsillar abscess, and
      healthy controls and found significantly increased levels of S100A8/A9 in
      patients with PTA. Furthermore, we could identify halitosis, trismus, uvula
      edema, and unilateral swelling of the arched palate to be characteristic symptoms
      for PTA. Using a combination of these characteristic symptoms and S100A8/A9
      levels, we developed a PTA score as an objective and appropriate tool to
      differentiate between peritonsillitis and peritonsillar abscess with a
      sensitivity of 92% and specificity of 93%.

PMID- 29180835
TI  - Laminated and infused Parafilm(r) - paper for paper-based analytical devices.
AB  - Numerous fabrication methods have been reported for microfluidic paper-based
      analytical devices (MUPADs) using barrier materials ranging from photoresist to
      wax. While these methods have been used with wide success, consistently producing
      small, high-resolution features using materials and methods that are compatible
      with solvents and surfactants remains a challenge. Two new methods are presented
      here for generating MUPADs with well-defined, high-resolution structures
      compatible with solvents and surfactant-containing solutions by partially or
      fully fusing paper with Parafilm(r) followed by cutting with a CO2 laser cutter.
      Partial fusion leads to laminated paper (l-paper) while the complete fusion
      results in infused paper (i-paper). Patterned structures in l-paper were
      fabricated by selective removal of the paper but not the underlying Parafilm(r)
      using a benchtop CO2 laser. Under optimized conditions, a gap as small as 137 +/-
      22 MUm could be generated. Using this approach, a miniaturized paper 384-zone
      plate, consisting of circular detection elements with a diameter of 1.86 mm, was
      fabricated in 64 * 43 mm2 area. Furthermore, these ablation-patterned substrates
      were confirmed to be compatible with surfactant solutions and common organic
      solvents (methanol, acetonitrile and dimethylformamide), which has been achieved
      by very few MUPAD patterning techniques. Patterns in i-paper were created by
      completely cutting out zones of the i-paper and then fixing pre-cut paper into
      these openings similar to the strategy of fitting a jigsaw piece into a puzzle.
      Upon heating, unmodified paper was readily sealed into these openings due to
      partial reflow of the paraffin into the paper. This unique and simple bonding
      method was illustrated by two types of 3D MUPADs, a push-on valve and a time
      gated flow distributor, without adding adhesive layers. The free-standing jigsaw
      patterned sheets showed good structural stability and solution compatibility,
      which provided a facile alternative method for fabricating complicated MUPADs.

PMID- 29180837
TI  - IL-33-ST2 Axis in Liver Disease: Progression and Challenge.
AB  - The new member of the IL-1 family, interleukin-33 (IL-33), participates in the
      progression of a variety of diseases through binding with its receptor ST2.
      Recently, much clinical evidence and experimental data have indicated that IL-33
      is associated with various liver diseases. This review primarily addresses the
      relationship between IL-33 and several hepatic diseases. IL-33 can alleviate high
      fat diet- (HFD-) induced hepatic steatosis and insulin resistance, and IL-33 acts
      as an alarmin, which quickly triggers the immune system to respond to virus
      invasion and toxic damage to the liver. However, when liver injury is chronic, IL
      33 promotes Th2 reactions and hepatic stellate cell (HSC) activity, facilitating
      progression to liver fibrosis. The complicated functions of IL-33 should be
      considered before its clinical application.

PMID- 29180836
TI  - Skin Immune Landscape: Inside and Outside the Organism.
AB  - The skin is an essential organ to the human body protecting it from external
      aggressions and pathogens. Over the years, the skin was proven to have a crucial
      immunological role, not only being a passive protective barrier but a network of
      effector cells and molecular mediators that constitute a highly sophisticated
      compound known as the "skin immune system" (SIS). Studies of skin immune
      sentinels provided essential insights of a complex and dynamic immunity, which
      was achieved through interaction between the external and internal cutaneous
      compartments. In fact, the skin surface is cohabited by microorganisms recognized
      as skin microbiota that live in complete harmony with the immune sentinels and
      contribute to the epithelial barrier reinforcement. However, under stress, the
      symbiotic relationship changes into a dysbiotic one resulting in skin disorders.
      Hence, the skin microbiota may have either positive or negative influence on the
      immune system. This review aims at providing basic background information on the
      cutaneous immune system from major cellular and molecular players and the impact
      of its microbiota on the well-coordinated immune responses in host defense.

PMID- 29180838
TI  - Suppressed Programmed Death 1 Expression on CD4+ and CD8+ T Cells in Psoriatic
      Patients.
AB  - Psoriasis is a chronic inflammatory disease mediated by T cell immunity.
      Programmed death 1 (PD-1), a coinhibitory receptor, plays an important role in
      immune regulation and maintaining peripheral tolerance. The aim of the study was
      to compare the expression of PD-1 on the peripheral T cells between psoriatic
      patients and healthy controls. The study included 75 psoriatic patients and 52
      healthy volunteers. The percentages and absolute numbers of CD3+, CD4+, CD8+,
      CD4+PD-1+, and CD8+PD-1+ T cells were analyzed using flow cytometry. The absolute
      numbers and percentages of CD4+PD-1+ and CD8+PD-1+ T cells were significantly
      decreased in the psoriatic patients in comparison with the control group. No
      significant correlations were found between the absolute numbers and percentages
      of CD4+PD-1+ or CD8+PD-1+ T cells and clinical characteristics of psoriasis.
      Decreased PD-1 expression on the T cells may be responsible for impaired negative
      regulation of immune response in psoriasis pathogenesis.

PMID- 29180839
TI  - Triggering Receptor Expressed on Myeloid Cells 2 Overexpression Inhibits
      Proinflammatory Cytokines in Lipopolysaccharide-Stimulated Microglia.
AB  - Microglia play an important role in mediating inflammatory processes in the
      central nervous system (CNS). Triggering receptor expressed on myeloid cells 2
      (TREM2) is a microglia-specific receptor and could decrease neuropathology in
      Alzheimer's disease (AD). However, the detailed mechanism remains unclear. This
      study was designed to elucidate the effect of TREM2 on microglia. We showed that
      lipopolysaccharide (LPS) stimulation significantly increases proinflammatory
      cytokines and suppressed TREM2 in microglia. In addition, TREM2 overexpression
      inhibited LPS-induced microglia activation and elevated M2 phenotype of
      microglia. Together, our results demonstrate that TREM2 overexpression reduced
      LPS-induced proinflammatory cytokine release in microglia and increased M2
      phenotype of microglia. These findings provide novel insights that the regulation
      of microglia polarization may be an approach for ameliorating microglia
      inflammation in neurodegenerative diseases.

PMID- 29180841
TI  - The Role of EUS-BD in the Management of Malignant Biliary Obstruction: The
      Indonesian Perspective.
AB  - Aims: To evaluate the success rate and related factors of endoscopic ultrasound
      guided-biliary drainage (EUS-BD). Material and Methods: We conducted a
      retrospective study among 24 patients with malignant biliary obstruction who
      underwent EUS-BD after failed ERCP from January 2015 to December 2016 in a
      tertiary health center. The bilirubin levels before and after the procedure were
      used to define the clinical success rate, while the stent deployment was used to
      define the technical success rate. We placed either transluminal biliary stents
      or transpapillary biliary stents. Results: Among 24 patients,
      choledochoduodenostomy technique was conducted in 23 patients (95.8%) and
      hepaticogastrostomy technique in 1 patient (4.2%). Transluminal stent placement
      was conducted in 23 patients, while transpapillary stent placement was conducted
      in 1 patient. The clinical success rate was 78.2% (18) in choledochoduodenostomy
      route and 100% (1) in hepaticogastrostomy route. EUS-BD was 2.37 times and 2.11
      times more likely to be successful in reducing the bilirubin level in patients
      with tumor of the head of pancreas and periampullary tumor, respectively, but not
      in cholangiocarcinoma. Conclusions: EUS-BD is an effective and efficient
      procedure to achieve biliary drainage among patients with malignant biliary
      obstruction after ERCP failure.

PMID- 29180840
TI  - Candida Chorioamnionitis Leads to Preterm Birth and Adverse Fetal-Neonatal
      Outcome.
AB  - Candida chorioamnionitis is rare but can lead to neonatal infection, high
      mortality, and neurodevelopmental impairment. We aimed to investigate maternal
      clinical features and perinatal outcomes and discuss future management
      strategies. We reviewed the medical records of women with Candida
      chorioamnionitis at our hospital over a 10-year period (n = 9) and previous
      published case reports and case series. The most prevalent Candida species was C.
      albicans (71.3% of the all cases). The most prevalent predisposing condition was
      preterm premature rupture of membranes (31/123, 25.2%), followed by pregnancy
      with a retained intrauterine contraceptive device (26/123, 21.1%) and pregnancy
      after in vitro fertilization (25/123, 20.3%). Preterm labor was the most common
      symptom (52/123, 42.3%), and only 13% of cases involved fever. Of the infants,
      27% of the singletons and 23.8% of the twins were born before 22 gestational
      weeks, while 60% of the singletons and 76.2% of the twins were born at 22-36
      weeks. The median birth weight of the babies born after 22 weeks was 1230 g. The
      mortality rates of the singletons and twins born after 22 weeks of gestation in
      the year 2000 or later were 28.6% and 52.4%, respectively. Antenatal treatment
      for Candida chorioamnionitis has not been established.

PMID- 29180842
TI  - Feasibility and Acceptability of Two Complementary and Alternative Therapies for
      Perceived Insufficient Milk in Mothers of Late Preterm and Early Term Infants.
AB  - Background: Complementary and alternative medicine (CAM) could be one option to
      address perceived insufficient milk (PIM), but there are few data comparing the
      effectiveness, acceptability, and safety of various CAM therapies. The purpose of
      this study was to describe and compare, among women delivering at 34-376/7 weeks,
      the feasibility and acceptability of two CAM interventions for treatment of PIM:
      (1) a meditation/relaxation intervention via an MP3 (Apple iPod Shuffle(c))
      player and (2) a commercially available combination-blend herbal supplement
      (Motherlove: More Milk Plus Alcohol Free(r)). Materials and Methods: After
      randomization, over 9 days, women received three home visits from a lactation
      consultant, recorded pre/post intervention test weights and expressed milk
      volume, tracked daily breastfeeding behavior, and completed an end-of-study
      interview about the interventions. Women in each group were offered the other
      group's intervention on study day 9. Breastfeeding status and intervention
      continuation were assessed at 2 months. Results: Of 183 women screened, 11 were
      eligible, enrolled into, and completed the 9-day trial. Six women were randomized
      to the herbal supplement and 5 to meditation. One participant (meditation)
      stopped breastfeeding on study day 8. At 2 months, 3 of 6 women assigned to the
      herbal supplement and 3 of 5 women assigned to meditation were still
      breastfeeding; 1 (herbal supplement) was exclusively breastfeeding. Most
      participants were adherent to the prescribed protocols for both interventions.
      Interventions were generally perceived as safe, with benefits not necessarily
      related to increased milk supply. Conclusion: Mothers of late preterm and early
      term infants who had PIM found the CAM interventions acceptable and safe. The
      effect of CAM therapies on breastfeeding outcomes, with and without in-home
      lactation assistance, requires further investigation.

PMID- 29180843
TI  - Visual performance, reading ability and patient satisfaction after implantation
      of a diffractive trifocal intraocular lens.
AB  - Purpose: To evaluate visual outcome, reading performance, contrast sensitivity,
      and patient satisfaction after cataract surgery with implantation of a
      diffractive trifocal intraocular lens (IOL). Patients and methods: A total of 42
      eyes (21 patients) underwent cataract surgery with implantation of the trifocal
      IOL AT LISA tri 839MP. Visual acuity, contrast sensitivity, and patient
      satisfaction were evaluated 3 months postoperatively. Reading performance was
      evaluated at 3 months postoperatively with the MNREAD charts. Results: All eyes
      achieved a 3-month postoperative monocular uncorrected distance visual acuity of
      0.10 logMAR or better (Snellen 20/25). Likewise, 97.62% and 85.71% of eyes
      achieved a postoperative monocular uncorrected intermediate, and near visual
      acuity of 0.20 logMAR (Snellen 20/30) or better. All patients achieved
      postoperative binocular uncorrected distance visual acuity, uncorrected
      intermediate, and uncorrected near visual acuity of 0.20 logMAR (Snellen 20/30)
      or better. Mean photopic reading acuity and speed were 0.24+/-0.07 logMAR and
      177.61+/-20.67 words per minute, respectively. Postoperative contrast sensitivity
      values were within the ranges of normality for all spatial frequencies evaluated.
      Postoperative spectacle independence and patient satisfaction was very high, with
      most of the patients reporting a good or very good visual quality at far,
      intermediate, and near distances. All patients would choose the same lens again.
      Conclusion: The evaluated trifocal IOL provides an effective restoration of the
      visual function after cataract surgery, with high levels of distance,
      intermediate, and near visual acuity, strong reading performance, and patient
      satisfaction.

PMID- 29180844
TI  - Vitreoretinal interface abnormalities in diabetic macular edema and effectiveness
      of anti-VEGF therapy: an optical coherence tomography study.
AB  - Purpose: To study vitreoretinal interface (VRI) abnormalities in diabetic macular
      edema (DME) and the influence of these on the effectiveness of intravitreal anti
      vascular endothelial growth factor (VEGF) therapy. Methods: VRI status and
      central retinal thickness (CRT) were evaluated using line and 3D-reference scans
      obtained using spectral domain-optical coherence tomography RTVue-100 before and
      1 month after intravitreal anti-VEGF injection (IVI). VRI status was categorized
      into five subgroups: normal VRI, retinal surface wrinkling associated with the
      eccentric epiretinal membrane (ERM), ERM involving the macular center,
      vitreomacular adhesion (VMA), and vitreomacular traction (VMT). Results: A total
      of 105 eyes of 89 patients were included in the study. One month after IVI, the
      mean change of CRT in normal VRI eyes and eyes with VRI abnormalities was 
      128.0+/-144.7 um and -53.0+/-96.4 um (p<0.05), respectively. The mean change of
      CRT 1 month after IVI in each subgroup with VRI abnormalities, apart from the
      subgroup with retinal wrinkling associated with eccentric ERM, was statistically
      significantly lower compared to the eyes with normal VRI (p<0.05). Conclusion:
      VRI abnormalities significantly reduce the effectiveness of intravitreal anti
      VEGF therapy in eyes with DME. Eyes with noticeable changes of VRI, including ERM
      involving the macular center, VMA, and VMT have a poorer response to anti-VEGF
      therapy compared to eyes with normal VRI or eccentric ERM.

PMID- 29180845
TI  - Clinical outcomes of endoscope-assisted vitrectomy for treatment of
      rhegmatogenous retinal detachment.
AB  - Summary: We evaluated the clinical outcomes for ophthalmic endoscope-assisted
      vitrectomy in consecutive patients with uncomplicated rhegmatogenous retinal
      detachment (RRD). The primary success rate was 98.4% (125/127) without performing
      a posterior drainage retinotomy or using perfluorocarbon liquids (PFCL) for
      subretinal fluid drainage. Purpose: To investigate the clinical outcomes of
      endoscope-assisted vitrectomy in patients with uncomplicated RRD. Methods: We
      examined 127 eyes from consecutive patients who underwent repair of RRD by 23- or
      25-gauge endoscope-assisted vitrectomy, with a minimum follow-up of 3 months.
      Eyes with the following criteria were excluded: Giant retinal tears, grade C
      proliferative vitreoretinopathy, dense vitreous hemorrhage, retinal detachment
      secondary to other ocular diseases, and prior retinal or vitreous surgery. All
      cases underwent subretinal fluid drainage, endolaser photocoagulation and fundus
      inspection were performed under ophthalmic endoscopic observation. Success rate,
      visual acuity, surgery time and complications were evaluated. Results: Primary
      and final success rate was 98.4% (125/127) and 100% (127/127), respectively,
      Surgery time was 59.6+/-26.3 minutes. The best-corrected visual acuity
      significantly improved from 20/100 to 20/20 (P<0.0001). There were 2 cases (1.6%)
      of creation of a peripheral drainage retinotomy and 4 cases (3.1%) of using PFCL
      to suppress movement of the detached retina, but there were no cases of creation
      of a posterior drainage retinotomy or using PFCL for subretinal fluid drainage.
      There was 1 case of presumed endophthalmitis after surgery. There were 12
      hypotonous cases at postoperative day 1 and one of them needed additional scleral
      sutures at postoperative day 4 for prolonged hypotony. Conclusion: The present
      study demonstrated the efficacy of endoscope-assisted vitrectomy for patients
      with uncomplicated RRD. To perform endoscope-assisted vitrectomy safely,
      sufficient closure of sclerotomies is necessary at the end of surgery.

PMID- 29180846
TI  - Different fixation targets affect retinal sensitivity obtained by microperimetry
      in normal individuals.
AB  - Purpose: To determine the differences in the retinal sensitivities obtained by
      microperimetry with a single cross or a circular fixation target in normal
      individuals. Methods: Thirty-two eyes of 16 healthy volunteers (mean age 28.9+/
      1.4 years, range 24-44 years) were studied. The retinal sensitivity of the
      central 0 degrees and of the mean central 2 degrees consisting of 8 points were
      determined independently using the two different fixation targets with
      Microperimeter 3. The Goldmann III stimulus with a luminance of 1.0 cd/m2 was
      presented for 200 ms on a white background. Results: The retinal sensitivity of
      the central 0 degrees was significantly better with the circular target than that
      with the cross target (P=0.003, right eyes; P=0.001, left eyes). The mean retinal
      sensitivity in the central 2 degrees was not significantly different between the
      cross and circular fixation targets. (P=0.07, right eyes; P=0.08, left eyes).
      Conclusion: These results indicate that the circular fixation target is a better
      target to use to evaluate the central retinal sensitivity. The difference in the
      retinal sensitivity is most likely due to the cross fixation target overlapping
      the test stimulus target.

PMID- 29180847
TI  - Optic disc segmentation for glaucoma screening system using fundus images.
AB  - Segmenting the optic disc (OD) is an important and essential step in creating a
      frame of reference for diagnosing optic nerve head pathologies such as glaucoma.
      Therefore, a reliable OD segmentation technique is necessary for automatic
      screening of optic nerve head abnormalities. The main contribution of this paper
      is in presenting a novel OD segmentation algorithm based on applying a level set
      method on a localized OD image. To prevent the blood vessels from interfering
      with the level set process, an inpainting technique was applied. As well an
      important contribution was to involve the variations in opinions among the
      ophthalmologists in detecting the disc boundaries and diagnosing the glaucoma.
      Most of the previous studies were trained and tested based on only one opinion,
      which can be assumed to be biased for the ophthalmologist. In addition, the
      accuracy was calculated based on the number of images that coincided with the
      ophthalmologists' agreed-upon images, and not only on the overlapping images as
      in previous studies. The ultimate goal of this project is to develop an automated
      image processing system for glaucoma screening. The disc algorithm is evaluated
      using a new retinal fundus image dataset called RIGA (retinal images for glaucoma
      analysis). In the case of low-quality images, a double level set was applied, in
      which the first level set was considered to be localization for the OD. Five
      hundred and fifty images are used to test the algorithm accuracy as well as the
      agreement among the manual markings of six ophthalmologists. The accuracy of the
      algorithm in marking the optic disc area and centroid was 83.9%, and the best
      agreement was observed between the results of the algorithm and manual markings
      in 379 images.

PMID- 29180848
TI  - Safety and efficacy of the addition of pertuzumab to T-DM1 +/- taxane in patients
      with HER2-positive, locally advanced or metastatic breast cancer: a pooled
      analysis.
AB  - Background: The aim of this review was to systematically evaluate the safety and
      efficacy of the addition of pertuzumab to trastuzumab emtansine (T-DM1) +/-
      taxane in patients with human epidermal growth factor receptor 2 (HER2)-positive,
      locally advanced breast cancer (LABC) or metastatic breast cancer (MBC).
      Materials and methods: Several databases were searched for relevant clinical
      trials. The study characteristics, details of adverse events (AEs) and details of
      treatment efficacy were extracted for analysis. Results: Six studies with 996
      patients were included. Common AEs of T-DM1 + pertuzumab +/- taxane included
      fatigue, diarrhea, nausea, epistaxis, peripheral neuropathy, increased aspartate
      transaminase (AST), increased alanine transaminase (ALT) and thrombocytopenia.
      Major grade >=3 AEs of T-DM1 + pertuzumab +/- taxane included thrombocytopenia,
      neutropenia, fatigue, increased ALT, anemia and peripheral neuropathy. The
      addition of pertuzumab to T-DM1 +/- taxane led to higher risks of diarrhea
      (especially grade >=3 diarrhea), rash and vomiting, and decreased risks of
      thrombocytopenia and grade >=3 increased AST. The relative risks of the addition
      of pertuzumab to T-DM1 +/- taxane for objective response (1.068, 95% CI 0.945
      1.207) and clinical benefit (1.038, 95% CI 0.974-1.106) were not statistically
      significant. Conclusion: Common AEs should be carefully monitored in HER2
      positive LABC or MBC patients treated with T-DM1 + pertuzumab +/- taxane. The
      addition of pertuzumab to T-DM1 +/- taxane showed noninferior, but not superior,
      objective response rate and clinical benefit rate. However, more studies are
      needed to further verify these findings.

PMID- 29180849
TI  - Adjuvant immunotherapy of dendritic cells and cytokine-induced killer cells is
      safe and enhances chemotherapy efficacy for multiple myeloma in China: a meta
      analysis of clinical trials.
AB  - Objective: The aim of this study was to systematically evaluate the efficacy and
      safety of the combination of dendritic cells and cytokine-induced killer cells
      (DC-CIK) adjuvant immunotherapy and chemotherapy in the treatment of multiple
      myeloma (MM). Methods: Clinical trials were gathered by searching Web of Science,
      PubMed, Embase, Cochrane Library, Wanfang, and CNKI database. Outcome
      measurements including therapeutic efficacy, prognosis, immune function, and
      adverse events were extracted and evaluated. Results: A total of 12 trials
      including 594 MM patients were involved in this study for statistical analysis.
      Results indicated that compared to chemotherapy alone, the combination of DC-CIK
      immunotherapy with chemotherapy significantly improved patients' overall response
      rate (ORR, odds ratio [OR] =2.77, 95% confidence interval [CI] =1.88-4.10,
      P<0.00001), disease control rate (DCR, OR =2.90, CI =1.72-4.90, P<0.0001), and
      life quality (P<0.00001). The combined therapy showed advantages over
      chemotherapy alone in prognostic indicators including percentage of tumor cells
      (P=0.04), serum levels of beta2-microglobin (P<0.0001), M protein (P<0.00001),
      and creatinine (P<0.0001), and 24 h urine light chains (P<0.00001). After
      combined treatment, CD4+ lymphocyte subsets' percentages, CD4+/CD8+ ratio, and
      cytokines levels of AgNOR, IFN-gamma, IL-2, and IL-12 were significantly
      increased (P<0.05), whereas CD8+ and CD4+CD25+ percentages and IL-4, IL-6, IL-10,
      and TGF-beta levels were obviously decreased (P<0.01), indicating a recovered
      immune condition. Conclusion: Adjuvant DC-CIK immunotherapy enhances the efficacy
      of chemotherapy for MM and improves prognosis probably by reconstructing immune
      function.

PMID- 29180850
TI  - Role of nebulized glycopyrrolate in the treatment of chronic obstructive
      pulmonary disease.
AB  - In the upcoming years, the proportion of elderly patients with chronic
      obstructive pulmonary disease (COPD) will increase, according to the
      progressively aging population and the increased efficacy of the pharmacological
      treatments, especially considering the management of chronic comorbidities. The
      issue to prescribe an appropriate inhalation therapy to COPD patients with
      significant handling or coordination difficulties represents a common clinical
      experience; in the latter case, the choice of an inadequate inhalation device may
      jeopardize the adherence to the treatment and eventually lead to its
      ineffectiveness. Treatment options that do not require particular timing for
      coordination between activation and/or inhalation or require high flow thresholds
      to be activated should represent the best treatment option for these patients.
      Nebulized bronchodilators, usually used only in acute conditions such as COPD
      exacerbations, could fulfill this gap, enabling an adequate drug administration
      during tidal breathing and without the need for patients' cooperation. However,
      so far, only short-acting muscarinic antagonists have been available for
      nebulization. Recently, a nebulized formulation of the inhaled long-acting
      muscarinic antagonist glycopyrrolate, delivered by means of a novel proprietary
      vibrating mesh nebulizer closed system (SUN-101/eFlow(r)), has progressed to
      Phase III trials and is currently in late-stage development as an option for
      maintenance treatment in COPD. The present critical review describes the current
      knowledge about the novel nebulizer technology, the efficacy, safety, and
      critical role of nebulized glycopyrrolate in patients with COPD. To this end,
      PubMed, ClinicalTrials.gov, Embase, and Cochrane Library have been searched for
      relevant papers. According to the available results, the efficacy and
      tolerability profile of nebulized glycopyrrolate may represent a valuable and
      dynamic treatment option for the chronic pharmacological management of patients
      with COPD.

PMID- 29180851
TI  - Differences of statin activity in 2D and 3D pancreatic cancer cell cultures.
AB  - Purpose: To evaluate the anticancer activity of lovastatin (LOVA), mevastatin
      (MEVA), pitavastatin (PITA), and simvastatin (SIMVA) in 2D and 3D models of three
      human pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, and PANC-1). Methods: The
      effect of statins on cell viability was estimated by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide test. The activity of statins in 3D pancreatic
      cancer cell cultures was examined by measuring the size change of spheroids. The
      type of cell death was identified by cell staining with Hoechst 33342 and
      propidium iodide. The activity of statins on the clonogenicity of cancer cells
      was tested by evaluating the effect on the colony-forming ability of cells.
      Results: The rank order of the activity of tested statins on cell viability was
      as follows: PITA > SIMVA > LOVA > MEVA. Among the tested statins, PITA had the
      greatest effect on cell viability (half maximal effective concentration values
      after 72 h on BxPC-3, MIA PaCa-2, and PANC-1 cells were 1.4+/-0.4 MUM, 1.0+/-0.2
      MUM, and 1.0+/-0.5 MUM, respectively). PITA also showed the strongest effect on
      tumor spheroid growth. Statins suppressed the colony formation of cancer cells.
      PITA demonstrated the greatest reduction in colony size and number. Apoptosis and
      necrosis assay results showed that at lower concentrations statins mostly induced
      cell death through apoptosis, whereas higher concentrations of compounds
      activated also necrotic processes. Conclusion: Statins, especially PITA,
      demonstrate an anticancer activity against pancreatic cancer cell lines BxPC-3,
      MIA PaCa-2, and PANC-1 in both 2D and 3D models.

PMID- 29180852
TI  - In silico-based identification of human alpha-enolase inhibitors to block cancer
      cell growth metabolically.
AB  - Unlimited growth of cancer cells requires an extensive nutrient supply. To meet
      this demand, cancer cells drastically upregulate glucose uptake and metabolism
      compared to normal cells. This difference has made the blocking of glycolysis a
      fascinating strategy to treat this malignant disease. alpha-enolase is not only
      one of the most upregulated glycolytic enzymes in cancer cells, but also
      associates with many cellular processes or conditions important to cancer cell
      survival, such as cell migration, invasion, and hypoxia. Targeting alpha-enolase
      could simultaneously disturb cancer cells in multiple ways and, therefore, is a
      good target for anticancer drug development. In the current study, more than 22
      million chemical structures meeting the criteria of Lipinski's rule of five from
      the ZINC database were docked to alpha-enolase by virtual screening. Twenty-four
      chemical structures with docking scores better than that of the enolase
      substrate, 2-phosphoglycerate, were further screened by the absorption,
      distribution, metabolism, excretion, and toxicity (ADMET) properties prediction.
      Four of them were classified as non-mutagenic, non-carcinogenic, and capable of
      oral administration where they showed steady interactions to alpha-enolase that
      were comparable, even superior, to the currently available inhibitors in
      molecular dynamics (MD) simulation. These compounds may be considered promising
      leads for further development of the alpha-enolase inhibitors and could help
      fight cancer metabolically.

PMID- 29180853
TI  - New insights into frequency and contents of fear of cancer progression/recurrence
      (FOP/FCR) in outpatients with colorectal carcinoma (CRC) receiving oral
      capecitabine: a pilot study at a comprehensive cancer center.
AB  - Background: Fear of cancer progression/recurrence (FOP/FCR) is considered one of
      the most prevalent sources of distress in cancer survivors and associated with
      lower quality of life and functional impairment. Detailed measures of FOP/FCR are
      needed because little is known about the knowledge of FOP/FCR, its associations
      with the patient-doctor relationship, and the rate of adequate therapy.
      Colorectal cancer (CRC) is one of the most prevalent cancer entities, and oral
      capecitabine is widely prescribed as treatment. Therefore, we initiated a pilot
      study to expand the literature on FOP/FCR in CRC outpatients receiving
      capecitabine and to generate hypotheses for future investigations. Methods: This
      study included 58 patients treated at a comprehensive cancer center. FOP/FCR was
      assessed with the Fear of Progression Questionnaire (FOP-Q-SF). Satisfaction with
      the relationships with doctors was assessed with the Patient-Doctor Relationship
      Questionnaire-9 (PRDQ-9). Levels of side effects were rated by the patients on a
      visual analog scale. Clinical data were extracted from the charts. Results: A
      total of 19 out of 58 patients (36%) suffered from FOP/FCR according to our
      assessment. Levels of FOP/FCR seemed to be mostly moderate to high. Only four out
      of the 19 distressed patients (21%) were treated accordingly. Typical side
      effects of oncological treatment were associated with higher FOP/FCR.
      Satisfaction with doctor-patient relationships was not associated with FOP/FCR.
      Regarding single items of FOP/FCR, three out of the five most prevalent fears
      were associated with close relatives. Discussion: FOP/FCR occurred frequently in
      more than one in three patients, but was mostly untreated in this sample of
      consecutive outpatients with CRC receiving oral capecitabine. In detail, most
      fears were related to family and friends. In addition to an unmet need of
      patients, our data indicate sources of distress not considered thus far. If
      replicated in larger studies, results may help to inform intervention development
      and improve patient care.

PMID- 29180854
TI  - Antimicrobial characterization of silver nanoparticle-coated surfaces by "touch
      test" method.
AB  - Bacterial infections, especially by antimicrobial resistant (AMR) bacteria, are
      an increasing problem worldwide. AMR is especially a problem with health care
      associated infections due to bacteria in hospital environments being easily
      transferred from patient to patient and from patient to environment, and thus,
      solutions to prevent bacterial transmission are needed. Hand washing is an
      effective tool for preventing bacterial infections, but other approaches such as
      nanoparticle-coated surfaces are also needed. In the current study, direct and
      indirect liquid flame spray (LFS) method was used to produce silver nanoparticle
      coated surfaces. The antimicrobial properties of these nanoparticle surfaces were
      evaluated with the "touch test" method against Escherichia coli and
      Staphylococcus aureus. It was shown in this study that in glass samples one
      silver nanoparticle-coating cycle can inhibit E. coli growth, whereas at least
      two coating cycles were needed to inhibit S. aureus growth. Silver nanoparticle
      coated polyethylene (PE) and PE terephthalate samples did not inhibit bacterial
      growth as effectively as glass samples: three nanoparticle-coating cycles were
      needed to inhibit E. coli growth, and more than 30 coating cycles were needed
      until S. aureus growth was inhibited. To conclude, with the LFS method, it is
      possible to produce nanostructured large-area antibacterial surfaces which show
      antibacterial effect against clinically relevant pathogens. Results indicate that
      the use of silver nanoparticle surfaces in hospital environments could prevent
      health care-associated infections in vivo.

PMID- 29180855
TI  - Aural stimulation with capsaicin ointment improved swallowing function in elderly
      patients with dysphagia: a randomized, placebo-controlled, double-blind,
      comparative study.
AB  - Objective: The aim of this study was to assess whether aural stimulation with
      ointment containing capsaicin improves swallowing function in elderly patients
      with dysphagia. Study design: A randomized, placebo-controlled, double-blind,
      comparative study. Settings: Secondary hospital. Patients and methods: Twenty
      elderly dysphagic patients with a history of cerebrovascular disorder or
      Parkinson's disease were randomly divided into two groups: 10 receiving aural
      stimulation with 0.025% capsaicin ointment and 10 stimulated with placebo. The
      ointments were applied to the external auditory canal with a cotton swab. Then,
      swallowing of a bolus of blue-dyed water was recorded using transnasal
      videoendoscopy, and the swallowing function was evaluated according to both
      endoscopic swallowing scoring and Sensory-Motor-Reflex-Clearance (SMRC) scale.
      Results: The sum of endoscopic swallowing scores was significantly decreased 30
      and 60 min after a single administration in patients treated with capsaicin, but
      not with placebo. Reflex score, but not Sensory, Motion and Clearance scores, of
      the SMRC scale was significantly increased 5, 30 and 60 min after single
      administration in patients treated with capsaicin, but not with placebo. No
      patient showed signs of adverse effects. Conclusion: As capsaicin is an agonist
      of the transient receptor potential vanilloid 1 (TRPV1), these findings suggest
      that improvement of the swallowing function, especially glottal closure and cough
      reflexes, in elderly dysphagic patients was due to TRPV1-mediated aural
      stimulation of vagal Arnold's nerve with capsaicin, but not with a nonspecific
      mechanical stimulation with a cotton swab.

PMID- 29180856
TI  - Effects of comprehensive geriatric assessment on physical fitness in an acute
      medical setting for frail elderly patients.
AB  - Introduction: Frail elderly people often use emergency care. During
      hospitalization, physical decline is common, implying an increased risk of
      adverse health outcomes. Comprehensive Geriatric Assessment (CGA) has been shown
      to be beneficial for these patients in hospital care. However, there is very
      limited evidence about the effects on physical fitness. The aim was to compare
      effects on physical fitness in the acute care of frail elderly patients at a CGA
      unit versus conventional care, 3 months after discharge. Patients and methods: A
      clinical, prospective, controlled trial with two parallel groups was conducted.
      Patients aged >=75 years, assessed as frail and in need of inpatient care, were
      assigned to a CGA unit or conventional care. Measurements of physical fitness,
      including handgrip strength (HS), timed up-and-go (TUG), and the 6-minute walk
      test (6-MWT) were made twice, at the hospital index care period and at the 3
      month follow-up. Data were analyzed as the mean change from index to the 3-month
      follow-up, and dichotomized as decline versus stability/improvement in physical
      fitness. Results: In all, 408 participants, aged 85.7+/-5.4 years, were included.
      The intervention group improved significantly in all components of physical
      fitness. The controls improved in TUG and declined in HS and 6-MWT. When the
      changes were dichotomized the intervention group declined to a lesser extent; HS
      p<0.001, 6-MWT p<0.001, TUG p<0.003. The regression analysis showed the following
      odds ratios (ORs) for how these outcomes were influenced by the intervention; HS
      OR 4.4 (confidence interval [CI] 95% 2.2-9.1), 6-MWT OR 13.9 (CI 95% 4.2-46.2),
      and TUG OR 2.5 (CI 95% 1.1-5.4). Conclusion: This study indicates that the acute
      care of frail elderly patients at a CGA unit is superior to conventional care in
      terms of preserving physical fitness at 3 months follow-up. CGA management may
      positively influence outcomes of great importance for these patients, such as
      mobility, strength, and endurance.

PMID- 29180858
TI  - The impact of age and preoperative health-related quality of life on patient
      reported improvements after total hip arthroplasty.
AB  - Background: Total hip arthroplasty (THA) is a common surgical procedure and
      approximately 9,500 of these surgeries are performed annually in Denmark. The
      operation is considered effective and successful with respect to complications,
      mortality, and implant survival. However, using patient-reported outcome
      measures, up to 10% of patients are not satisfied with the outcome of their
      operation. To address this, it is important to find out why some patients
      experience impaired outcomes after THA. The purpose of this study was to
      investigate the impact of age and preoperative health-related quality of life
      (HRQoL) on improvements in HRQoL after THA. Methods: A cohort study was conducted
      with follow-up at 3 and 12 months. Patients were included from September 2008 to
      December 2013. We analyzed 1,283 THA cases. HRQoL was measured using the EuroQol
      5 Domain. Analyses were carried out with multiple linear regression and adjusted
      for relevant variables available in the data set. Results: A significant positive
      association was found between age and HRQoL outcomes for patients who underwent
      THA at both 3 (beta [regression coefficient] 0.0026, confidence interval [CI]
      0.0013; 0.0039, p<0.001) and 12 (beta 0.0020 CI 0.0008; 0.0032, p=0.001) months
      of follow-up. A clinically relevant change was achieved with an increase in age
      of 12-15 years. A significant negative association was found between preoperative
      HRQoL and HRQoL outcomes at both 3 (beta -0.841 CI -0.886; -0.795, p<0.001) and
      12 (beta -0.804 CI -0.844; -0.764, p<0.001) months of follow-up. Conclusion:
      Contrary to our expectations, older patients had more improvements in HRQoL
      outcomes after THA. A high preoperative HRQoL seems to inhibit improvements in
      HRQoLs after THA.

PMID- 29180857
TI  - Association between apolipoprotein E gene polymorphism and mild cognitive
      impairment: a meta-analysis.
AB  - A number of published case-control studies reported that the apolipoprotein E
      (ApoE) gene polymorphism was associated with the mild cognitive impairment (MCI).
      However, previous reports still remain conflicting. To estimate the association
      between ApoE polymorphism and MCI susceptibility, we searched the electronic
      databases including PubMed, Wanfang, CNKI (China National Knowledge
      Infrastructure), VIP, and EMBASE to retrieve all available studies. A total of 18
      studies with 2,004 cases and 3,705 controls were included in this meta-analysis.
      The pooled analysis based on selected studies showed that statistically
      significant risk association was found between ApoE gene polymorphism and MCI in
      overall population (epsilon4 vs epsilon3: odds ratio [OR] =2.38, 95% confidence
      interval [CI]: 2.11-2.68; epsilon4/epsilon4 vs epsilon3/epsilon3: OR =4.45, 95%
      CI: 3.06-6.48; epsilon2/epsilon4 vs epsilon3/epsilon3: OR =2.57, 95% CI: 1.77
      3.73; epsilon3/epsilon4 vs epsilon3/epsilon3: OR =2.31, 95% CI: 1.99-2.69).
      However, no significant association was detected in two genetic models: epsilon2
      versus epsilon3 (OR =0.90, 95% CI: 0.77-1.05) and epsilon2/epsilon2 versus
      epsilon3/epsilon3 (OR =0.91, 95% CI: 0.50-1.65). Furthermore, ApoE
      epsilon2/epsilon3 genotype provided a slight protection for MCI in overall
      population (epsilon2/epsilon3 vs epsilon3/epsilon3: OR =0.80, 95% CI: 0.66-0.97).
      In the stratified analysis based on ethnicity, similar results were also observed
      in Chinese population (significant risk: epsilon4 vs epsilon3: OR =2.52, 95% CI:
      2.19-2.90; epsilon4/epsilon4 vs epsilon3/epsilon3: OR =5.45, 95% CI: 3.41-8.70;
      epsilon2/epsilon4 vs epsilon3/epsilon3: OR =2.59, 95% CI: 1.74-3.86;
      epsilon3/epsilon4 vs epsilon3/epsilon3: OR =2.34, 95% CI: 1.97-2.79; slight
      protection: epsilon2/epsilon3 vs epsilon3/epsilon3: OR =0.79, 95% CI: 0.64-0.98;
      no association: epsilon2 vs epsilon3: OR =0.92, 95% CI: 0.78-1.09; and
      epsilon2/epsilon2 vs epsilon3/epsilon3: OR =1.04, 95% CI: 0.55-1.99). In summary,
      this meta-analysis of 5,709 subjects suggested that ApoE epsilon4 allele was
      associated with an increased risk of MCI. In addition, ApoE epsilon2/epsilon3
      genotype provided a slight protection for MCI.

PMID- 29180859
TI  - Hyponatremia in the elderly: challenges and solutions.
AB  - Decreased serum sodium concentration is a rather frequent electrolyte disorder in
      the elderly population because of the presence of factors contributing to
      increased antidiuretic hormone, the frequent prescription of drugs associated
      with hyponatremia and also because of other mechanisms such as the "tea and
      toast" syndrome. The aim of this review is to present certain challenges in the
      evaluation and treatment of hyponatremia in the elderly population and provide
      practical solutions. Hyponatremia in elderly subjects is mainly caused by drugs
      (more frequently thiazides and antidepressants), the syndrome of inappropriate
      antidiuretic hormone secretion (SIAD) or endocrinopathies; however, hyponatremia
      is multifactorial in a significant proportion of patients. Special attention is
      needed in the elderly population to exclude endocrinopathies as a cause of
      hyponatremia before establishing the diagnosis of SIAD, which then requires a
      stepped diagnostic approach to reveal its underlying cause. The treatment of
      hyponatremia depends on the type of hyponatremia. Special attention is also
      needed to correct serum sodium levels at the appropriate rate, especially in
      chronic hyponatremia, in order to avoid the osmotic demyelination syndrome. In
      conclusion, both the evaluation and the treatment of hyponatremia pose many
      challenges in the elderly population.

PMID- 29180860
TI  - Different impacts of respiratory symptoms and comorbidities on COPD-specific
      health-related quality of life by COPD severity.
AB  - Background: Patients with chronic obstructive pulmonary disease (COPD) often have
      poor health-related quality of life (HRQoL) that is disproportionate to their
      degree of airflow limitation. This study evaluated the association between St
      George's Respiratory Questionnaire for COPD (SGRQ-C) score and forced expiratory
      volume in one second and investigated the factors responsible for high SGRQ-C
      score according to severity of airflow limitation. Methods: Data from 1,264 COPD
      patients were obtained from the Korean COPD Subgroup Study (KOCOSS) cohort.
      Patients were categorized into two groups according to severity of airflow
      limitation: mild-to-moderate and severe-to-very severe COPD groups. We evaluated
      the clinical factors associated with high SGRQ-C score (>=25) in each COPD
      patient group. Results: Of the 1,264 COPD patients, 902 (71.4%) had mild-to
      moderate airflow limitation and 362 (28.6%) had severe-to-very severe airflow
      limitation. Of the mild-to-moderate COPD patients, 59.2% (534/902) had high SGRQ
      C score, while 80.4% (291/362) of the severe-to-very severe COPD patients had
      high SGRQ-C score. The association between SGRQ-C score and post-bronchodilator
      forced expiratory volume in one second (% predicted) was very weak in the mild-to
      moderate COPD patients (r=-0.103, p=0.002) and weak in the severe-to-very severe
      COPD patients (r=-0.219, p<0.001). Multiple logistic regression analysis revealed
      that age, being an ex- or current smoker, lower level of education, cough,
      dyspnea, and number of comorbidities with congestive heart failure,
      hyperlipidemia, and depression were significantly associated with high SGRQ-C
      score in mild-to-moderate COPD patients. In comparison, being an ex-smoker and
      having respiratory symptoms including sputum and dyspnea were significant factors
      associated with high SGRQ-C score in severe-to-very severe COPD patients.
      Conclusions: In addition to the respiratory symptoms of dyspnea and cough, high
      SGRQ-C score was associated with extra-pulmonary comorbidities in mild-to
      moderate COPD patients. However, only respiratory symptoms such as sputum and
      dyspnea were significantly associated with high SGRQ-C score in severe-to-very
      severe COPD patients. This indicates the need for an improved management strategy
      for relieving respiratory symptoms in COPD patients with poor HRQoL. In addition,
      attention should be paid to extra-pulmonary comorbidities, especially in mild-to
      moderate COPD patients with poor HRQoL.

PMID- 29180861
TI  - Healthy lifestyle behaviors among individuals with chronic obstructive pulmonary
      disease in urban and rural communities in China: a large community-based
      epidemiological study.
AB  - Background: Lifestyle modification is one of the most cost-effective strategies
      in self-management and secondary prevention of chronic obstructive pulmonary
      disease (COPD). However, the prevalence of healthy lifestyle behaviors in COPD
      patients in China remains unclear. The objective of this study was to examine the
      rates of healthy lifestyle behaviors including smoking cessation, regular
      exercise, and healthy diet in community population with COPD in China. Methods:
      We recruited 46,285 individuals aged 35-70 years from 115 urban and rural
      communities in 12 provinces of China from 2005 to 2009. We recorded the smoking
      status, physical activity intensity, and quality of diet for all spirometry
      diagnosed COPD patients by standardized questionnaires. Results: Among 3,690
      individuals with COPD, 18.2% (95% confidence interval [CI], 13.0-24.9) quitted
      smoking, 27.1% (95% CI, 24.7-29.7) exercised often, and 34.8% (95% CI, 31.8-38.0)
      ate high-quality diet. More than half of the individuals followed one or less key
      healthy lifestyle, and only 8.4% (95% CI, 7.0-10.0) followed all of the three
      healthy behaviors. Urban residents had significant higher rates of smoking
      cessation (23.5% [95% CI, 17.3-31.1] vs 14.4% [95% CI, 9.9-20.5], p=0.0008),
      regular exercise (45.6% [95% CI, 42.4-48.8] vs 14.0% [95% CI, 12.1-16.2],
      p<0.0001), and healthy diet (38.5% [95% CI, 35.5-41.6] vs 32.2% [95% CI, 29.2
      35.4], p=0.0013) than rural residents. Age, sex, education level, body mass
      index, respiratory symptoms, and family income were associated with healthy
      living, and the strength of associations varied between urban and rural areas.
      Conclusion: There is a large gap between the anticipated rate and the real
      participation in healthy lifestyle behaviors in Chinese adults with COPD,
      especially in rural communities. Simple and effective strategies are warranted to
      improve patients' lifestyle in China.

PMID- 29180862
TI  - Smoking cessation affects the natural history of COPD.
AB  - Background: Cigarette smoking is the most commonly encountered and readily
      identifiable risk factor for COPD. However, it is not clear which quantitative
      factors related to smoking influence the prognosis of COPD patients. Methods: A
      total of 204 patients with a long-term history of smoking were enrolled into this
      study and followed up for 5 years. Patients were divided into "death" or
      "survival" groups based on follow-up results and "quitting-smoking" or
      "continuing-smoking" groups based on whether they gave up smoking. Results:
      Patients in the death group had a longer smoking time, lower prevalence of
      quitting smoking, later onset of COPD symptoms, older age at quitting smoking,
      lower forced expiratory volume in one second (FEV1) % predicted, and lower ratio
      of FEV1/forced vital capacity. Age, age at quitting smoking, and FEV1% predicted
      were independently associated with mortality from COPD. Compared to the
      continuing-smoking group, the quitting-smoking group had a lower mortality rate,
      longer course of COPD, earlier onset of COPD symptoms, and lower residual volume
      percent predicted. During the 5-year follow-up, 113 deaths were recorded
      (quitting-smoking group: n=92; 40 deaths; continuing-smoking group: n=112; 73
      deaths). The mortality risk remained significantly higher in the continuing
      smoking group than the quitting-smoking group (log-rank test, 13.59; P=0.0002).
      Conclusion: Smoking time may be related to the mortality rate from COPD. Smoking
      cessation has the greatest capacity to influence the natural history of COPD.

PMID- 29180863
TI  - Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong
      retention time for pulmonary drug delivery.
AB  - High drug resistance, poor water solubility, short half-life, and low local drug
      concentration are obstacles for successful delivery of chemotherapeutic drugs for
      lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary
      delivery is proposed. However, use of NPs is limited by the particle size range
      for pulmonary drug delivery considering that NPs cannot be deposited directly
      into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs)
      will result in suitable particle sizes and retain the advantages of nanodrugs
      after redispersion when applied in pulmonary delivery. We report the development
      of novel NPs in the form of PMs loaded with paclitaxel (PTX) and quercetin (QUE)
      double drugs based on the synthesis of oleic acid-conjugated chitosan (OA-CTS)
      for pulmonary delivery. This approach is aimed toward prolonging PTX retention
      time in the presence of QUE and bypassing P-glycoprotein drug efflux pumps. NPs
      loaded with PTX or QUE were prepared with 11% substitution degree using OA-CTS as
      the carrier by ionic cross-linking method, which NPs loaded with PTX or QUE were
      used in the preparation of PMs by spray-drying. The diameters of the PMs ranged
      from 1 to 5 MUm which had uniform size range. Scanning electron microscopy showed
      that PMs were polymers formed by a large number of NPs and readily redispersed
      (after redispersion, size of NPs ranged between 250 and 350 nm) in water within 1
      h. PMs displayed slow-release characteristics at pH 4.5 and 7.4. The in vivo
      pharmacokinetic and biodistribution studies suggested that PMs exhibit prolonged
      circulation time and a markedly high accumulation in the lung. The obtained
      results indicate that PMs can serve as a promising pulmonary delivery system for
      combined pharmacotherapy using hydrophobic anticancer drugs.

PMID- 29180864
TI  - A nanoliposome-based photoactivable drug delivery system for enhanced cancer
      therapy and overcoming treatment resistance.
AB  - Recently, stimuli-responsive drug delivery systems (DDSs) with high
      spatial/temporal resolution bring many benefits to cancer treatment. However,
      cancer cells always develop ways to resist and evade treatment, ultimately limit
      the treatment efficacy of the DDSs. Here, we introduce photo-activated
      nanoliposomes (PNLs) that impart light-induced cytotoxicity and reversal of drug
      resistance in synchrony with a photoinitiated and rapid release of antitumor
      drug. The PNLs consist of a nanoliposome doped with a photosensitizer
      (hematoporphyrin monomethyl ether [HMME]) in the lipid bilayer and an antitumor
      drug doxorubicin (DOX) encapsulated inside. PNLs have several distinctive
      capabilities: 1) carrying high loadings of DOX and HMME and releasing the
      payloads in a photo-cleavage manner with high spatial/temporal resolution at the
      site of actions via photocatalysis; 2) reducing drug efflux in MCF-7/multidrug
      resistance cells via decreasing the level of P-glycoprotein induced by
      photodynamic therapy (PDT); 3) accumulating in tumor site taking advantage of the
      enhanced permeability and retention effect; and 4) combining effective
      chemotherapy and PDT to exert much enhanced anticancer effect and achieving
      significant tumor regression in a drug-resistant tumor model with little side
      effects.

PMID- 29180865
TI  - Fabrication of large-pore mesoporous Ca-Si-based bioceramics for bone
      regeneration.
AB  - Our previous study revealed that mesoporous Ca-Si-based materials exhibited
      excellent osteoconduction because dissolved ions could form a layer of
      hydroxycarbonate apatite on the surface of the materials. However, the biological
      mechanisms underlying bone regeneration were largely unknown. The main aim of
      this study was to evaluate the osteogenic ability of large-pore mesoporous Ca-Si
      based bioceramics (LPMSCs) by alkaline phosphatase assay, real-time PCR analysis,
      von Kossa, and alizarin red assay. Compared with large-pore mesoporous silica
      (LPMS), LPMSCs had a better effect on the osteogenic differentiation of dental
      pulp cells. LPMSC-2 and LPMSC-3 with higher calcium possessed better osteogenic
      abilities than LPMSC-1, which may be related to the calcium-sensing receptor
      pathway. Furthermore, the loading capacity for recombinant human platelet-derived
      growth factor-BB was satisfactory in LPMSCs. In vivo, the areas of new bone
      formation in the calvarial defect repair were increased in the LPMSC-2 and LPMSC
      3 groups compared with the LPMSC-1 and LPMS groups. We concluded that LPMSC-2 and
      LPMSC-3 possessed both excellent osteogenic abilities and satisfactory loading
      capacities, which may be attributed to their moderate Ca/Si molar ratio.
      Therefore, LPMSCs with moderate Ca/Si molar ratio might be potential alterative
      grafts for craniomaxillofacial bone regeneration.

PMID- 29180867
TI  - Immigration-related mental health disorders in refugees 5-18 years old living in
      Turkey.
AB  - Purpose: This study assessed early-onset psychiatric disorders and factors
      related to these disorders in a group of refugee children after immigration due
      to war. Materials and methods: This study was conducted between January 2016 and
      June 2016. Clinical interviews were conducted with 89 children and their
      families, and were performed by native speakers of Arabic and Persian who had
      been primarily educated in these languages and were living in Turkey. A strengths
      and difficulties questionnaire (SDQ) that had Arabic and Persian validity and
      reliability was applied to both children and their families. Independent
      variables for cases with and without a psychiatric disorder were analyzed using
      the chi2 test for categorical variables, Student's t-test for those that were
      normally distributed, and Mann-Whitney U-test for data that were not normally
      distributed. Data that showed significant differences between groups who had a
      psychiatric disorder and on common effects in emerging psychiatric disorders were
      analyzed through binary logistic regression analysis. Results: A total of 89
      children and adolescents were interviewed within the scope of the study. The mean
      age of cases was 9.96+/-3.98 years, and 56.2% (n=50) were girls, while 43.8%
      (n=39) were boys. Among these children, 47 (52.8%) had come from Syria, 27
      (30.3%) from Iraq, 14 (15.7%) from Afghanistan, and 1 (1.1%) from Iran. A
      psychiatric disorder was found in 44 (49.4%) of the children. A total of 26
      children were diagnosed with anxiety disorders, 12 with depressive disorders, 8
      with trauma and related disorders, 5 with elimination disorders, 4 with attention
      deficit/hyperactivity disorder, and 3 with intellectual disabilities. It was
      determined that seeing a dead or injured person during war/emigration and the
      father's unemployment increased the risk of psychopathology. The OR was 7.077
      (95% CI 1.722-29.087) for having seen a dead or injured individual and 4.51 (95%
      GA 1.668-12.199) for father's employment status. Conclusion: Within the context
      of war and emigration, these children try to cope with the negative circumstances
      they experience prior to migration, as well as the despair they see their parents
      experience.

PMID- 29180866
TI  - Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide
      derivatized [60]fullerene in a murine model of breast adenocarcinoma.
AB  - [60]Fullerene is a highly versatile nanoparticle (NP) platform for drug delivery
      to sites of pathology owing to its small size and both ease and versatility of
      chemical functionalization, facilitating multisite drug conjugation, drug
      targeting, and modulation of its physicochemical properties. The prominent and
      well-characterized role of the enhanced permeation and retention (EPR) effect in
      facilitating NP delivery to tumors motivated us to explore vascular transport
      kinetics of a water-soluble [60]fullerene derivatives using intravital microscopy
      in an immune competent murine model of breast adenocarcinoma. Herein, we present
      a novel local and global image analysis of vascular transport kinetics at the
      level of individual tumor blood vessels on the micron scale and across whole
      images, respectively. Similar to larger nanomaterials, [60]fullerenes displayed
      rapid extravasation from tumor vasculature, distinct from that in normal
      microvasculature. Temporal heterogeneity in fullerene delivery to tumors was
      observed, demonstrating the issue of nonuniform delivery beyond spatial
      dimensions. Trends in local region analysis of fullerene biokinetics by
      fluorescence quantification were in agreement with global image analysis. Further
      analysis of intratumoral vascular clearance rates suggested a possible enhanced
      penetration and retention effect of the fullerene compared to a 70 kDa vascular
      tracer. Overall, this study demonstrates the feasibility of tracking and
      quantifying the delivery kinetics and intratumoral biodistribution of fullerene
      based drug delivery platforms, consistent with the EPR effect on short timescales
      and passive transport to tumors.

PMID- 29180868
TI  - The efficacy of antipsychotics for prolonged delirium with renal dysfunction.
AB  - Aim: Delirium is commonly encountered in daily clinical practice. To identify
      predictors influencing outcomes, we retrospectively examined the characteristics
      of inpatients with delirium who required psychiatric medication during
      hospitalization. Methods: We extracted all new inpatients (n=523) consulted for
      psychiatric symptoms at Fukushima Medical University Hospital between October
      2011 and September 2013. We selected 203 inpatients with delirium diagnosed by
      psychiatrists. We analyzed data from 177 inpatients with delirium who received
      psychiatric medication. We defined an "early improvement group" in which delirium
      resolved in <=3 days after starting psychiatric medication, and a "prolonged
      group" with delirium lasting for >3 days. Among the 83 inpatients with renal
      dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2), we defined
      an "early improvement group with renal dysfunction" in which delirium resolved in
      <=3 days after starting psychiatric medication and a "prolonged group with renal
      dysfunction" with delirium lasting for >3 days. We then examined differences
      between groups for different categorical variables. Results: Dose of
      antipsychotic medication at end point was significantly lower in the prolonged
      group with renal dysfunction than in the early improvement group with renal
      dysfunction. Conclusion: The results suggest that maintaining a sufficient dose
      of antipsychotics from an early stage may prevent prolongation of delirium even
      in inpatients with renal dysfunction.

PMID- 29180869
TI  - ECMO as an effective rescue therapeutic for fulminant myocarditis complicated
      with refractory cardiac arrest.
AB  - Fulminant myocarditis (FM) is a life-threatening disease in children. With a
      rapid, progressive course of deterioration, it causes refractory
      cardiorespiratory failure even with optimal clinical intervention. We present the
      case of a 9-year-old girl with FM complicated by cardiogenic shock, malignant
      arrhythmia, and refractory cardiac arrest. She received effective cardiopulmonary
      resuscitation, therapeutic hypothermia, and other supportive treatments. However,
      the patient rapidly worsened into pulseless ventricular tachycardia and
      refractory cardiac arrest. Therefore, we performed extracorporeal membrane
      oxygenation (ECMO) to establish spontaneous circulation after the failure of
      standard resuscitation measures. The girl recovered with intact cardiac and
      neurocognitive functions after continued ECMO treatment for 221 hours. Therefore,
      ECMO is an effective rescue therapeutics for FM, especially when complicated with
      refractory cardiac arrest.

PMID- 29180870
TI  - The effect of antiviral therapy on patients with hepatitis B virus-related
      hepatocellular carcinoma after curative resection: a systematic review and meta
      analysis.
AB  - Background and aim: Studies suggest that antiviral therapy performed after
      curative resection improves the postoperative prognosis of hepatitis B virus
      (HBV)-related hepatocellular carcinoma (HCC), but the evidence has been
      contradictory. The aim of this meta-analysis was to assess the effect of
      antiviral therapy with nucleoside analogs (NAs) after curative resection on the
      long-term postoperative survival of patients with HBV-related HCC. Materials and
      methods: MEDLINE, PubMed, Embase, and Cochrane Library were systematically
      searched up to August 2017 with no limits. Outcome measures were the primary
      parameter of overall survival (OS) after radical resection of HBV-related HCC and
      the secondary parameter of postoperative recurrence-free survival (RFS). Results:
      A total of 9,009 patients (2,546 of whom received antiviral therapy and 6,463
      received no treatment) were included. The pooled analysis revealed that antiviral
      therapy was associated with significantly improved OS (hazard ratio [HR]: 0.58;
      95% confidence interval [CI]: 0.51-0.67; P<0.00001) and RFS (HR: 0.68; 95% CI:
      0.63-0.74; P<0.00001). Moderate heterogeneity among studies for both OS and RFS
      was observed, which disappeared or decreased after pooling studies using one type
      of NA as antiviral drug. In the subgroup analysis, anti-viral therapy
      significantly prolonged both OS (HR: 0.69; 95% CI: 0.52-0.92; P=0.01) and RFS
      (HR: 0.58; 95% CI: 0.49-0.70; P<0.00001) in patients with high baseline HBV DNA
      level (>=20,000 IU/mL) with no heterogeneity, but not in patients with low
      baseline HBV DNA level (<20,000 IU/mL). Conclusion: Antiviral therapy with NAs
      confers significant survival benefits in patients with HBV-related HCC after
      curative resection, especially in patients with high baseline HBV DNA level
      (>=20,000 IU/mL).

PMID- 29180871
TI  - LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by
      regulating ZEB1 expression via miR-194.
AB  - Background: Chemoresistance is one of the major obstacles for cancer therapy in
      the clinic. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported
      as an oncogene in most malignancies such as lung cancer, esophageal cancer, and
      gastric cancer. This study is designed to investigate the function of NEAT1 in
      paclitaxel (PTX) resistance of ovarian cancer and its potential molecular
      mechanism. Patients and methods: The expressions of NEAT1 and miR-194 in ovarian
      cancer tissues and cells were estimated by quantitative real-time polymerase
      chain reaction (qRT-PCR). MTT, flow cytometry, and Western blot assays were used
      to assess the effect of NEAT1 on PTX resistance in PTX-resistant ovarian cancer
      cells. Luciferase reporter assay was applied to examine the association between
      NEAT1, zinc finger E-box-binding homeobox 1 (ZEB1) and miR-194. Xenograft tumor
      model was established to confirm the biological role of NEAT1 in PTX resistance
      of ovarian cancer in vivo. Results: NEAT1 was upregulated, and miR-194 was
      downregulated in PTX-resistant ovarian cancer tissues and cells. Functionally,
      NEAT1 knockdown enhanced cell sensitivity to PTX via promoting PTX-induced
      apoptosis in vitro. NEAT1 was identified as a molecular sponge of miR-194 to
      upregulate ZEB1 expression. Mechanistically, NEAT1-knockdown-induced PTX
      sensitivity was mediated by miR-194/ZEB1 axis. Moreover, NEAT1 knockdown improved
      PTX sensitivity of ovarian cancer in vivo. Conclusion: NEAT1 contributed to PTX
      resistance of ovarian cancer cells at least partly through upregulating ZEB1
      expression by sponging miR-194, elucidating a novel regulatory pathway of
      chemoresistance in PTX-resistant ovarian cancer cells and providing a possible
      long noncoding RNA (lncRNA)-targeted therapy for ovarian cancer.

PMID- 29180872
TI  - Therapeutic efficacy and safety of combined BRAF and MEK inhibition in patients
      with malignant melanoma: a meta-analysis.
AB  - Background: Recent clinical studies have shown that initial therapy with combined
      BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibition
      is more effective in metastatic melanoma than single-agent BRAF inhibitors.
      However, the response rates with single-agent BRAF are low. Thus, the objective
      of this study was to conduct a meta-analysis of randomized controlled trials to
      compare the efficacy and adverse events risk between mono-therapy and combination
      therapy. Materials and methods: Searches were made in PubMed and EMBASE
      electronic databases and conference abstracts published by the American Society
      of Clinical Oncology from 2000 to 2017. Outcomes included overall response,
      progression-free survival, and overall survival, as well as the incidence rate of
      adverse events. Results: Eight trials comprising 2,664 patients were included in
      the meta-analysis. Patients with combined therapies showed superior results
      compared to those with BRAF inhibitors alone for the following: overall response
      rate (combined relative risk [RR] =1.34, 95% confidence interval [95% CI]: 1.24
      1.45, P<0.00001), progression-free survival (combined hazards ratio [HR] =0.58,
      95% CI: 0.52-0.64, P<0.00001), and overall survival rate (combined HR =0.70, 95%
      CI: 0.62-0.80, P<0.00001). Patients with combination therapies had higher
      incidence of adverse events including pyrexia (combined RR =2.00, 95% CI: 1.40
      2.84), nausea (combined RR =1.41, 95% CI: 1.03-1.94), diarrhea (combined RR
      =1.50, 95% CI: 1.08-2.06), and vomiting (combined RR =1.87, 95% CI: 01.52-2.31)
      compared to those with BRAF inhibitors alone. Conclusion: These data suggested
      that the combined BRAF and MEK inhibition was associated with a significant
      improvement in overall response, progression-free survival, and overall survival,
      but increased the incidence of adverse events among the patients with BRAF V600
      mutated metastatic melanoma. Further large-scale, high-quality, placebo
      controlled, double-blind trials are needed to confirm this conclusion.

PMID- 29180873
TI  - In vitro study on anti-cancer properties of genistein in tongue cancer.
AB  - Purpose: Tongue cancer is an extremely aggressive disease and is characterized by
      a poor prognosis. It is a complex disease to treat and current therapies have
      produced mediocre results with many side effects. Some facts suggest that natural
      essences can support traditional cancer therapy by carrying out a synergistic
      function with chemotherapy. Therefore, we evaluated the antitumor effects of
      genistein on tongue carcinoma cells. Methods: Genistein 20, 50 and 100 uM were
      used for 24, 48 and 72 hours on 3 tongue carcinoma cell lines. xCELLigence system
      was used to evaluate the effects on cell adhesion, proliferation and to calculate
      IC50 values. Both MTT assay and Trypan blue assay were used to evaluate
      alterations in cell viability, scratch assay for cell migration and Western blot
      analysis for expression of some proteins. Results: Cell adhesion was inhibited
      especially between 20 and 50 uM of genistein treatment. Proliferation was reduced
      by 50% for treatments with 20 uM at 24 hours, with 20 or 50 uM at 48 and 50 uM at
      72 hours (P<0.0001). Viability tests confirmed a proportional reduction in
      concentration of genistein and duration of treatments. Even cell migration was
      reduced significantly (P<0.001). Genistein down-regulates vitronectin, OCT4 and
      survivin. Conclusion: This in vitro study clarifies the anti-tumor effect of
      genistein on tongue carcinoma. In vivo studies are needed to confirm these data
      and develop a suitable delivery system that is capable of acting directly on
      tumor.

PMID- 29180874
TI  - Expression and significance of B7-H3 and Tie-2 in the tumor vasculature of clear
      cell renal carcinoma.
AB  - Tumor angiogenesis is required for tumor growth and metastasis, and the Ang/Tie-2
      axis plays a pivotal role in angiogenesis. B7-H3, a new member of the B7 family
      of costimulatory molecules, has a critical function in the T-cell-mediated
      antitumor immune response, and abnormal tumor B7-H3 expression is frequently
      associated with a poor prognosis. However, the relationship between B7-H3 and
      angiogenesis in clear cell renal carcinoma (ccRCC) remains unclear. In this
      study, we used immunohistochemical methods to detect tumor vascular expression of
      B7-H3 and Tie-2 in tissue microarrays of 82 ccRCC patient samples. According to
      the results, B7-H3 is highly expressed in the tumor vascular endothelium of ccRCC
      and is associated with the ccRCC grade and tumor-node-metastasis (TNM) stage.
      Although vascular Tie-2 expression was also correlated with T stage and lymph
      node metastasis, it was not related to ccRCC grade or distant metastasis. The
      microvessel density (MVD) labeled by CD34 was correlated with tumor grade and TNM
      stage. Expression of B7-H3 and Tie-2 was positively correlated, and the levels
      were positively associated with the MVD. Additionally, immunofluorescence
      staining revealed coexpression of B7-H3 and Tie-2 in the vascular endothelia of
      ccRCC. Collectively, our findings suggest that expression of B7-H3 and Tie-2 in
      ccRCC tumor vasculature is closely related to the progression and prognosis of
      the disease. Furthermore, B7-H3 possibly promotes ccRCC angiogenesis through the
      Tie-2 pathway. Thus, B7-H3 might serve as an effective endothelial marker for
      ccRCC prognosis and become a promising target for ccRCC anti-angiogenic-targeted
      therapy.

PMID- 29180875
TI  - Effective treatment of low-dose decitabine in myelodysplastic
      syndrome/myeloproliferative neoplasms.
AB  - Objective: Primary myelofibrosis (PMF) is one of the Philadelphia negative
      myeloproliferative neoplasms (MPN). The main clinical features are obvious
      physical symptoms and symptomatic splenomegaly. It may be converse to leukemia
      and has a shortened life expectancy. Nowadays, the therapy for PMF is aimed at
      maintaining comfort and there is no curative treatment. PMF with myelodysplastic
      syndrome (MDS), called MDS/MPN-u, is rare and the treatment is complex. In this
      study, we want to discuss an effective treatment for MDS/MPN via a case report
      and literature review. Materials and methods: A female patient was diagnosed with
      MDS/MPN through bone marrow cytology, immunology, cell genetics, molecular
      biology, and pathology. She received thalidomide and prednisone as initial
      treatment. Ten months later, the first-line therapy had failed, she presented
      with clinically relevant pancytopenia and increased blasts in bone marrow.
      Because decitabine is one of the first-line treatments for MDS and the patient
      was frail, she received low-dose decitabine as second-line therapy. Decitabine
      was administered at 15 mg/m2 once a week for 3 weeks, in a 4 week cycle. If there
      was improvement the treatment interval was prolonged. Result: After one cycle,
      the blasts in bone marrow were decreased to 0.5%. After four cycles, she felt
      comfortable and hematological improvement was achieved. The treatment interval
      was prolonged. After eight cycles, the spleen reduced to 2 cm under the rib, and
      she achieved complete hematological remission. After ten cycles, the mutation of
      JAK2/V617F expression was decreased from 60.63% to 0.01%. During the therapy, the
      patient presented with grade III-IV hematological toxicity after the first two
      cycles, but there were no side effects after subsequent cycles. Conclusion: Our
      research showed that low-dose decitabine may be an effective treatment for
      MDS/MPN, especially in improving physical symptoms and achieving hematological
      remission. Besides, it may be possible to reverse positive JAK2 mutation.

PMID- 29180876
TI  - The effect of CYP2D6 *10 polymorphism on adjuvant tamoxifen in Asian breast
      cancer patients: a meta-analysis.
AB  - Objective: To evaluate the effect of CYP2D6 *10 polymorphism (C 100C>T,
      rs1065852) on clinical outcomes of female Asian breast cancer patients with
      tamoxifen adjuvant treatment. Methods: Meta-analysis of retrospective cohort
      studies published in July 2017 was performed. Fifteen studies with 1,794 Asian
      breast cancer patients were included, using strict eligibility requirements.
      Associations of disease-free survival (DFS), overall survival (OS) and recurrence
      rate after tamoxifen intake, with CYP2D6 *10 polymorphism were investigated
      through random effects models. Results: CYP2D6 *10 polymorphism was found to have
      effect on DFS and recurrence rate in various comparison models, but not on
      overall survival in the female Asian breast cancer patients. Conclusion: In
      conclusion, our meta-analysis suggests that significant association of *10/*10
      (TT) genotype with poorer DFS and recurrence exists in female Asian breast cancer
      patients with tamoxifen 20 mg/day adjuvant treatment. In the future, large and
      well-designed studies are required to illustrate the interactions of CYP2D6
      genetic variants, including *10 polymorphism and tamoxifen response on female
      breast cancer patients.

PMID- 29180878
TI  - Nimotuzumab combined with concurrent chemoradiotherapy benefits patients with
      advanced nasopharyngeal carcinoma.
AB  - Background: The potential benefits and possible risks associated with combined
      nimotuzumab and concurrent chemoradiotherapy in patients with advanced
      nasopharyngeal carcinoma (NPC) have yet to be determined. Methods: The databases
      PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang were
      systematically searched through February 2017 for studies comparing combined
      nimotuzumab and chemoradiotherapy versus chemoradiotherapy alone in the treatment
      of NPC. Primary outcomes were complete and partial responses, and the secondary
      outcome was adverse reactions. The random-effect model was used to pool relative
      risks (RRs) and 95% confidence intervals (CIs). Results: Nine randomized control
      trials and six cohort studies were included in the final analysis (n=1,015
      patients). Compared with chemoradiotherapy alone, chemoradiotherapy combined with
      nimotuzumab was associated with an increased response rate (RR =1.11, 95% CI:
      1.01-1.22). Combined treatment further reduced the occurrence rate of
      erythropenia (RR =0.11, 95% CI: 0.05-0.28) and neutropenia (RR =0.12, 95% CI:
      0.05-0.27). The differences in the rates of other complications were not
      significant. Conclusion: Nimotuzumab combined with concurrent chemoradiotherapy
      is more effective in patients with advanced NPC than chemoradiotherapy alone.
      Patients receiving combination therapy did not have a higher rate of adverse
      reactions. Nimotuzumab can thus be recommended as an adjunct therapy in patients
      with advanced NPC.

PMID- 29180877
TI  - Clinical significance of CMTM4 expression in hepatocellular carcinoma.
AB  - CMTM4 is the most conserved member of chemokine-like factor (CKLF)-like MARVEL
      transmembrane domain-containing (CMTM) family on chromosome 16q22.1, a locus that
      harbors a number of tumor-suppressor genes. In previous studies, CMTM4 was
      reported to be downregulated and exhibited tumor-suppressor activities by
      regulating cell growth and cell cycle in clear cell renal cell carcinoma.
      However, its roles in tumorigenesis of hepatocellular carcinoma (HCC) remain
      poorly studied. This study first investigated the expression of CMTM4 in HCC, and
      then examined the association between the expression of CMTM4 with the
      clinicopathological features and prognosis of HCC patients. It was found that
      CMTM4 was downregulated in HCC tissues, compared with matched adjacent nontumor
      tissues, as detected by immunohistochemistry. In addition, Kaplan-Meier survival
      analysis showed that the negative expression of CMTM4 was associated with
      decreased overall survival rates in patients with HCC. The results of this study
      suggest CMTM4 plays a role as a tumor suppressor in HCC and CMTM4 negative
      expression is a risk factor for poor prognosis of HCC.

PMID- 29180879
TI  - Male occult triple-negative breast cancer with dermatomyositis: a case report and
      review of the literature.
AB  - Occult breast cancer is defined by the presence of axillary metastases without an
      identifiable primary breast tumor. Here, we report a rare case of a male occult
      breast cancer with dermatomyositis. We performed a modified radical mastectomy
      consisting of whole breast mastectomy and axillary lymph node dissection.
      Immunohistochemistry and fluorescent in situ hybridization analyses demonstrated
      an adenocarcinoma likely of breast origin, which was an occult triple-negative
      breast cancer. Interestingly, the patient's previously noted periorbital
      dermatomyositis resolved promptly following surgical excision.

PMID- 29180880
TI  - Identification of COX5B as a novel biomarker in high-grade glioma patients.
AB  - Background: Malignant glioma is the second leading cause of cancer-related death
      worldwide, and is known to exhibit a high degree of heterogeneity in its
      deregulation of different oncogenic pathways. The molecular subclasses of human
      glioma are not well known. Thus, it is crucial to identify vital oncogenic
      pathways in glioma with significant relationships to patient survival. Methods:
      In this study, we devised a bioinformatics strategy to map patterns of oncogenic
      pathway activation in glioma, from the Gene Expression Omnibus (GEO).
      Bioinformatics analysis revealed that 749 genes were differentially expressed and
      classified into different glioma grades. Results: Using gene expression
      signatures, we identified three oncogenic pathways (MAPK signaling pathway, Wnt
      signaling pathway, and ErbB signaling pathway) deregulated in the majority of
      human glioma. Following gene microarray analysis, the gene expression profile in
      the differential grade glioma was further validated by bioinformatic analyses,
      with coexpression network construction. Furthermore, we found that cytochrome c
      oxidase subunit Vb (COX5B), the terminal enzyme of the electron transport chain,
      was the central gene in a coexpression network that transfers electrons from
      reduced cytochrome c to oxygen and, in the process, generates an electrochemical
      gradient across the mitochondrial inner membrane. The expression level of COX5B
      was then detected in 87 glioma tissues as well as adjacent normal tissues using
      immunohistochemistry. We found that COX5B was significantly upregulated in 67 of
      87 (77.0%) glioma and glioblastoma tissues, compared with adjacent tissue
      (p<0.01). Furthermore, statistical analysis showed the COX5B expression level was
      significantly associated with clinical stage and lymph node status, while there
      were no correlations between COX5B expression and age or tumor size. Conclusion:
      These data indicate that COX5B may be implicated in glioma pathogenesis and as a
      biomarker for identification of the pathological grade of glioma.

PMID- 29180881
TI  - Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma
      by suppressing the PI3K/AKT and NF-kappaB/COX-2 signaling pathways.
AB  - Glioblastoma (GBM) is a highly invasive and challenging primary tumor of the
      central nervous system (CNS), and currently available treatments provide limited
      benefits to patients with this disease. Therefore, the development of novel
      therapeutic targets and effective treatment strategies is essential. Nimustine
      hydrochloride (ACNU) is widely used as the standard chemotherapeutic agent and is
      frequently administered together with other chemotherapeutic agents in clinical
      studies. Curcumin, a natural polyphenolic compound, could potentially be combined
      with chemotherapeutics for cancer treatment; however, there are no reports of
      studies where ACNU and curcumin were combined for GBM treatment, and the
      mechanisms underlying their activity remain poorly understood. In the present
      study, we investigated the effects of combined treatment with curcumin and ACNU
      on GBM cells and found that it significantly enhanced the inhibition of cell
      proliferation, colony formation, migration, and invasion. In addition, co
      treatment with curcumin increased ACNU-induced apoptosis through enhancing the
      release of cytochrome c from the mitochondrial intermembrane space into the
      cytosol. Further, curcumin and ACNU acted synergistically in their antitumor
      effects by targeting N-cadherin/MMP2/9, PI3K/AKT, and NF-kappaB/COX-2 signaling.
      These results indicate that curcumin can enhance the anti-proliferation, anti
      migration, and proapoptotic activities of ACNU against GBM, and provide strong
      evidence that combined treatment with curcumin and ACNU has the potential to be
      an effective therapeutic option for GBM.

PMID- 29180882
TI  - Cytomembranic PD-L1 expression in locoregionally advanced nasopharyngeal
      carcinoma.
AB  - Background and objective: The aim of this study was to evaluate the expression of
      cytomembranic programmed death-ligand 1 (PD-L1) and its clinical significance in
      locoregionally advanced nasopharyngeal carcinoma (NPC). Patients and methods:
      Formalin-fixed, paraffin-embedded tissue biopsies from 85 patients with
      histological diagnosis of locoregionally advanced NPC treated with radical
      intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy were
      studied. By using immunohistochemistry staining, expressions of cytomembranic PD
      L1 on tumor cells were detected. Results: After a median follow-up duration of
      65.8 months, 7 (8.2%), 5 (5.9%), and 5 (5.9%) patients suffered from local
      failure, regional failure, and distant metastases, respectively. The 5-year local
      failure-free survival, regional failure-free survival, distant failure-free
      survival, and overall survival (OS) rates were 90.9%, 94.8%, 94.0%, and 92.2%,
      respectively. Our results revealed that a high expression of cytomembranic PD-L1
      was correlated with shorter OS (5y-OS: 82.5% vs 97.6%, P=0.022). In the
      multivariate analysis, only the cytomembranic PD-L1 was an independent prognostic
      factor for OS (hazard ratio: 6.176, 95% confidence interval, 1.166-32.710,
      P=0.032). Conclusion: Cytomembranic PD-L1 expression levels correlated with OS in
      locoregionally advanced NPC. Agreement between different methods is needed for
      further application of PD-L1 biomarker assays in NPC.

PMID- 29180883
TI  - Erratum: Toll-like receptors 7 and 8 expression correlates with the expression of
      immune biomarkers and positively predicts the clinical outcome of patients with
      melanoma [Corrigendum].
AB  - [This corrects the article on p. 4339 in vol. 10, PMID: 28919783.].

PMID- 29180885
TI  - Long-term effect of the insoluble thread-lifting technique.
AB  - Background: Although the thread-lifting technique for sagging faces has become
      more common and popular, medical literature evaluating its effects is scarce.
      Studies on its long-term prognosis are particularly uncommon. Patients and
      methods: One hundred individuals who had previously undergone insoluble thread
      lifting were retrospectively investigated. Photos in frontal and oblique views
      from the first and last visits were evaluated by six female individuals by
      guessing the patients' ages. The mean guessed age was defined as the apparent
      age, and the difference between the real and apparent ages was defined as the
      youth value. The difference between the youth values before and after the thread
      lift was defined as the rejuvenation effect and analyzed in relation to the time
      since the operation, the number of threads used and the number of thread-lift
      operations performed. Results: The rejuvenation effect decreased over the first
      year after the operation, but showed an increasing trend thereafter. The
      rejuvenation effect increased with the number of threads used and the number of
      thread-lift operations performed. Conclusion: The insoluble thread-lifting
      technique appears to be associated with both early and late effects. The
      rejuvenation effect appeared to decrease during the first year, but increased
      thereafter. A multicenter trial is necessary to confirm these findings.

PMID- 29180884
TI  - Redefining face contour with a novel anti-aging cosmetic product: an open-label,
      prospective clinical study.
AB  - Background: Skin aging is accelerated by multiple extrinsic factors: ultraviolet
      radiation, smoking and pollution increase oxidative activity, damaging cellular
      and extracellular components such as DNA, proteins, and lipids. With age,
      collagen and hyaluronic acid levels decline, resulting in loss of elasticity and
      moisture of the skin. Over time this damage leads to characteristic signs that
      make the skin look older: altered facial contour, sagging skin, wrinkles, and an
      uneven complexion. This study evaluated the anti-aging effects of a new facial
      cream formulated with carnosine, Alteromonas ferment extract, crosspolymer
      hyaluronic acid, and a tripeptide. Methods: An open-label intra-individual study
      to assess the anti-aging efficacy of the investigational product in 33 women aged
      45 to 65 years. The product was applied twice daily for 56 days. Facial contour
      and skin deformation, elasticity, hydration, and complexion were measured with
      specialized equipment at baseline and days 28 and 56. Additionally, subjects
      completed questionnaires at days 28 and 56 on the perceived efficacy and cosmetic
      characteristics of the product. Results: After 56 days of use of the
      investigational product, a redefining effect was observed, with a significant
      decrease in sagging jawline (7%). Skin was significantly more hydrated (12%),
      firmer (29%), and more elastic (20%) (P<0.001 for all). On complexion assessment,
      skin texture (a measure of skin smoothness) and spots (brown and red skin
      lesions) also improved significantly (12% and 6% decrease, respectively). In the
      subjective self-evaluation, the majority of subjects reported that the skin was
      visibly tightened and more elastic, flexible, and moisturized (91%, 88%, 91%, and
      90%, respectively). The product was well tolerated with no adverse events
      reported during the study. Conclusion: This new cosmetic product demonstrated
      anti-aging effects after 56 days of use, most notably a redefined facial contour
      and improved complexion. It is a safe and effective anti-aging product.

PMID- 29180886
TI  - Next generation of biologics for the treatment of Crohn's disease: an evidence
      based review on ustekinumab.
AB  - The limited efficacy of the currently available medical therapies in a proportion
      of patients with Crohn's disease has led to the research and development of
      molecules that can block new inflammatory pathways. Ustekinumab is a fully human
      IgG1 monoclonal antibody which targets the common p40 subunit of the cytokines
      interleukin-12 as well as interleukin-23. Consequently, the Th1 and Th17
      inflammatory responses are inhibited. Ustekinumab has been recently approved for
      its use in patients with Crohn's disease. Its efficacy and safety was initially
      proved in patients with psoriasis and psoriatic arthritis. More recently, three
      Phase III trials have confirmed its efficacy in patients with Crohn's disease
      refractory to anti-tumor necrosis factor therapy. This biologic agent appears
      safe, with no increased risk of infectious or malignant complications, and a low
      immunogenic profile.

PMID- 29180888
TI  - Association between serum concentration of 25-hydroxyvitamin D and community
      acquired pneumonia: a case-control study.
AB  - Background: Community-acquired pneumonia (CAP) is a common disease with
      significant morbidity and mortality. There is evidence that vitamin D deficiency
      can be associated with infectious diseases. The aim of this study was to compare
      the levels of vitamin D between patients with CAP and healthy controls. Methods:
      In a case-control study on 73 patients with CAP and 76 healthy controls, the
      serum concentration of 25-hydroxyvitamin D (25[OH]D) was measured. Severity and
      outcomes of disease and also duration of hospital stay were compared in patients
      with different levels of 25(OH)D. The severity of CAP was assessed using the CURB
      65 score (confusion, uremia, respiratory rate, low blood pressure, age >=65
      years) and was also reflected by the length of hospital stay, admission to
      intensive care unit (ICU), and 30-day mortality. Results: In total, 81.2% of the
      study population had vitamin D levels <30 ng/dL. The risk of pneumonia among
      subjects with deficient vitamin D levels was 3.69 (95% CI: 1.46, 9.31) times of
      those with sufficient vitamin D level (P=0.006). Prevalence of severe deficiency
      of vitamin D in scores three and four of CURB-65 (59.38%), was far more than
      scores one and two (31.71%). Also, results indicated patients with severe
      deficiency had a higher risk for ICU admission, 30-day mortality, and longer
      hospitalization stay, but these were not statistically significant. Conclusion:
      According to findings, a low level of 25(OH)D is associated with a higher
      incidence of CAP and more severe disease. It is recommended to pay more attention
      to vitamin D deficiency in infectious diseases, particularly in CAP patients.

PMID- 29180887
TI  - Ingested capsaicinoids can prevent low-fat-high-carbohydrate diet and high-fat
      diet-induced obesity by regulating the NADPH oxidase and Nrf2 pathways.
AB  - Objective: Capsaicinoids (CAPs), most commonly found in chili peppers, have a
      multitude of pharmacological and physiological effects, such as anti
      inflammation, antioxidant, and anticancer effects. In the present study, we set
      out to investigate the hypothesis that CAPs mitigate obesity in rats and the
      possible mechanisms thereof. Materials and methods: Rats were divided into six
      groups, including control (+/-10 mg CAPs/kg body weight [BW]), low-fat-high
      sucrose diet (+/-10 mg CAPs/kg BW), and high-fat diet (+/-10 mg CAPs/kg BW).
      Blood samples and liver and aortic tissues were taken at the end of the study.
      Results: CAPs supplementation significantly reduced hyperglycemia and
      hyperlipidemia (P<0.001) and ameliorated oxidative damage by reducing
      malondialdehyde concentrations in serum and liver and by increasing total
      antioxidant capacity in serum induced by the low-fat-high-sucrose and high-fat
      diets (P<0.001 for all). CAPs also depressed levels of NFkappaB p65, gp91phox,
      and p22phox, essential components of NADPH oxidase, in the aorta of rats.
      However, levels of Nrf2, Sirt1, and endothelial nitric oxide synthase were
      significantly increased in the aorta. Conclusion: CAPs may at least partially
      reduce adverse effects due to high-fat diet and sucrose consumption through
      regulation of energy metabolism, oxidative stress, and proteins involved in
      vasoprotection.

PMID- 29180889
TI  - Risk of respiratory depression with opioids and concomitant gabapentinoids.
AB  - Introduction: The combination of opioids and central nervous system depressants
      such as benzodiazepines and barbiturates has an additive effect on the frequency
      of oversedation and respiratory depression requiring naloxone use in hospitalized
      patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed
      with opioids for their opioid-sparing and adjuvant analgesic effects. There is
      limited literature on the risk of respiratory depression due to the combination
      of opioids and gabapentinoids requiring naloxone administration. Methods: This
      retrospective study evaluated patients who were prescribed opioids and at least
      one dose of naloxone between March 1, 2014 and September 30, 2016. The primary
      objective of this study was to compare the frequency of respiratory depression
      among patients who received naloxone and opioids (non-gabapentinoid group) with
      those who received naloxone, opioids, and gabapentinoids (gabapentinoid group).
      Secondary objectives included comparing the association of oversedation, using
      the Pasero Opioid-induced Sedation Scale, and various risk factors with those in
      the gabapentinoid group. Results: A total of 153 patient episodes of naloxone
      administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups)
      in 125 unique patients were included in the study. For the primary objective,
      there were 33 episodes of respiratory depression associated with the non
      gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression
      with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed
      a significant association between respiratory depression and surgery in the
      previous 24 hours (p=0.036) as well as respiratory depression and age >65 years
      (p=0.031) for patients in the non-gabapentinoid group compared to the
      gabapentinoid group. Conclusion: There was no significant association of
      respiratory depression in the gabapentinoid group versus the non-gabapentinoid
      group. There was an increased risk of respiratory depression in the gabapentinoid
      group, specifically in patients who had surgery within the previous 24 hours.

PMID- 29180890
TI  - A retrospective study on analgesic requirements for thoracoscopic surgery
      postoperative pain.
AB  - Background: Thoracoscopic surgery (TS) has been performed as a minimally invasive
      procedure since the beginning of the 1990s. This has led to a dramatic change in
      the postoperative condition of these patients, facilitating early ambulation and
      easier management of postoperative pain. However, empirical evidence on
      postoperative pain management after TS is limited. The aims of this study were to
      determine the efficacy and adequacy of postoperative analgesic medications and to
      simplify the choice of additional drugs based on a numerical rating scale (NRS).
      Materials and methods: A retrospective study of patients who underwent TS was
      performed to evaluate postoperative pain, analgesia requirements, and the number
      of drugs needed during the perioperative period based on the NRS score. Results:
      Of the 524 patients, mild pain was noted in 87% patients on the day of the
      operation and in 75.6% patients on ambulation. The mean NRS score was 1.83+/-1.49
      on the day of the operation and 2.73+/-1.75 on ambulation. An NRS score of 3 on
      both the day of operation and on ambulation was defined as the necessary
      condition for improved pain management. Multivariate analysis showed that high
      surgical stress significantly influenced pain scores. Reduction in pain with an
      NRS score of >=1 was significant with the addition of pentazocine hydrochloride
      (p<0.01) and flurbiprofen (p<0.01). Interestingly, the addition of tramadol was
      borderline efficacious (p=0.05) in patients with an NRS score of >3 on
      ambulation. Conclusion: A small number of patients have moderate-to-severe pain
      after TS. Tramadol demonstrated borderline efficacy in controlling postoperative
      intense pain with an NRS score of >=3.

PMID- 29180891
TI  - Effect of oxycodone patient-controlled intravenous analgesia after cesarean
      section: a randomized controlled study.
AB  - Background: Oxycodone is a semisynthetic MU-opioid receptor agonist with a
      potentially good analgesic efficacy in visceral pain. This study aims to compare
      the efficacy of oxycodone with sufentanil patient-controlled intravenous
      analgesia (PCIA). Methods: One hundred and twenty primiparas undergoing elective
      cesarean section were randomized into four groups by different drugs of PCIA:
      group S (sufentanil 100 MUg), group OS1 (sufentanil 70 MUg, oxycodone 30 mg),
      group OS2 (sufentanil 50 MUg, oxycodone 50 mg), and group O (oxycodone 100 mg).
      Ramosetron 0.3 mg was added to each group. In all groups, drugs were diluted to
      100 mL and managed with a continuous infusion of 1 mL.h-1, a bolus dose of 2 mL,
      and a lockout interval of 15 min. The maximum dose of PCIA per hour was 10 mL.
      After surgery, pain scores, PCIA doses, and side effects were compared among
      groups. Results: At all time points (6, 12, and 24 h after surgery), Numerical
      Rating Scale (NRS) of uterine cramping pain (NRS-U) scores in group O were lower
      than those in groups OS1 and S (P<0.008) and NRS-U scores in groups OS2 and OS1
      were lower than that in group S (P<0.008). NRS of moving into the sitting
      position (NRS-S) scores in group O were lower than those in the other groups
      (P<0.008). NRS-S scores in group OS2 were lower than those in groups OS1 and S
      (P<0.008). At 12 and 24 h after surgery, NRS of incision pain at rest (NRS-R)
      scores in group O were lower than those in the other groups (P<0.008). At all
      time points, NRS-R scores in group OS2 were lower than those in groups OS1 and S
      (P<0.008). The number of PCIA boluses and amount of opioid consumption in group O
      were lower than those in groups OS1 and S at all time points (P<0.008).
      Conclusion: Oxycodone PCIA may be more effective than sufentanil PCIA for pain
      relief after cesarean section but the incidence of side effects needs further
      investigation.

PMID- 29180892
TI  - Does self-perception of sensitivity to pain correlate with actual sensitivity to
      experimental pain?
AB  - Background: People often state that they are "sensitive" or "insensitive" to
      pain. However, the accuracy and clinical relevance of such statements is unclear.
      Objective: The aim of this study was to search for associations between self
      perception of sensitivity to pain and experimental pain measures, including known
      psychophysical inhibitory or excitatory pain paradigms. Subjects and methods:
      Subjective sensitivity to pain was reported by 75 healthy participants and
      included three self-perceived variables: pain threshold, pain sensitivity and
      pain intensity in response to a hypothetical painful event (hypothetical pain
      intensity [HPI]). Experimental pain measures consisted of thermal pain threshold
      ( degrees C), suprathreshold thermal pain intensity (Visual Analog Scale, 0-100)
      and the psychophysical paradigms of conditioned pain modulation (CPM) and
      temporal summation (TS), representing inhibitory and excitatory pain processes,
      respectively. Results: No significant correlations were found between self
      perceived pain threshold or pain sensitivity and any of the experimental pain
      measures. In contrast, the reported HPI correlated with thermal pain threshold (r
      = -0.282; p = 0.014), suprathreshold thermal pain intensity (r = 0.367; p =
      0.001) and CPM (r = 0.233; p = 0.044), but not with TS. Conclusion: Self
      perception of pain sensitivity articulated by intangible expressions such as pain
      threshold or pain sensitivity is unrelated to actual sensitivity to experimental
      pain. In contrast, when measured by intensity of a hypothetical painful event
      (HPI), sensitivity to pain is associated with some, but not all, experimental
      pain reports. Further studies are needed for better understanding of these
      associations and their potential clinical significance.

PMID- 29180893
TI  - Identification of key genes and pathways associated with neuropathic pain in
      uninjured dorsal root ganglion by using bioinformatic analysis.
AB  - Purpose: Neuropathic pain is a complex chronic condition occurring post-nervous
      system damage. The transcriptional reprogramming of injured dorsal root ganglia
      (DRGs) drives neuropathic pain. However, few comparative analyses using high
      throughput platforms have investigated uninjured DRG in neuropathic pain, and
      potential interactions among differentially expressed genes (DEGs) and pathways
      were not taken into consideration. The aim of this study was to identify changes
      in genes and pathways associated with neuropathic pain in uninjured L4 DRG after
      L5 spinal nerve ligation (SNL) by using bioinformatic analysis. Materials and
      methods: The microarray profile GSE24982 was downloaded from the Gene Expression
      Omnibus database to identify DEGs between DRGs in SNL and sham rats. The
      prioritization for these DEGs was performed using the Toppgene database followed
      by gene ontology and pathway enrichment analyses. The relationships among DEGs
      from the protein interactive perspective were analyzed using protein-protein
      interaction (PPI) network and module analysis. Real-time polymerase chain
      reaction (PCR) and Western blotting were used to confirm the expression of DEGs
      in the rodent neuropathic pain model. Results: A total of 206 DEGs that might
      play a role in neuropathic pain were identified in L4 DRG, of which 75 were
      upregulated and 131 were downregulated. The upregulated DEGs were enriched in
      biological processes related to transcription regulation and molecular functions
      such as DNA binding, cell cycle, and the FoxO signaling pathway. Ctnnb1 protein
      had the highest connectivity degrees in the PPI network. The in vivo studies also
      validated that mRNA and protein levels of Ctnnb1 were upregulated in both L4 and
      L5 DRGs. Conclusion: This study provides insight into the functional gene sets
      and pathways associated with neuropathic pain in L4 uninjured DRG after L5 SNL,
      which might promote our understanding of the molecular mechanisms underlying the
      development of neuropathic pain.

PMID- 29180894
TI  - Cortical mapping of painful electrical stimulation by quantitative
      electroencephalography: unraveling the time-frequency-channel domain.
AB  - The goal of this study was to capture the electroencephalographic signature of
      experimentally induced pain and pain-modulating mechanisms after painful
      peripheral electrical stimulation to determine one or a selected group of
      electrodes at a specific time point with a specific frequency range. In the first
      experiment, ten healthy participants were exposed to stimulation of the right
      median nerve while registering brain activity using 32-channel
      electroencephalography. Electrical stimulations were organized in four blocks of
      20 stimuli with four intensities - 100%, 120%, 140%, and 160% - of the electrical
      pain threshold. In the second experiment, 15 healthy participants received
      electrical stimulation on the dominant median nerve before and during the
      application of a second painful stimulus. Raw data were converted into the time
      frequency domain by applying a continuous wavelet transform. Separated domain
      information was extracted by calculating Parafac models. The results demonstrated
      that it is possible to capture a reproducible cortical neural response after
      painful electrical stimulation, more specifically at 250 milliseconds
      poststimulus, at the midline electrodes Cz and FCz with predominant delta
      oscillations. The signature of the top-down nociceptive inhibitory mechanisms is
      delta-activity at 235 ms poststimulus at the prefrontal electrodes. This study
      presents a methodology to overcome the a priori determination of the regions of
      interest to analyze the brain response after painful electrical stimulation.

PMID- 29180895
TI  - Postoperative pain management in the postanesthesia care unit: an update.
AB  - Acute postoperative pain remains a major problem, resulting in multiple
      undesirable outcomes if inadequately controlled. Most surgical patients spend
      their immediate postoperative period in the postanesthesia care unit (PACU),
      where pain management, being unsatisfactory and requiring improvements, affects
      further recovery. Recent studies on postoperative pain management in the PACU
      were reviewed for the advances in assessments and treatments. More objective
      assessments of pain being independent of patients' participation may be
      potentially appropriate in the PACU, including photoplethysmography-derived
      parameters, analgesia nociception index, skin conductance, and pupillometry,
      although further studies are needed to confirm their utilities. Multimodal
      analgesia with different analgesics and techniques has been widely used. With
      theoretical basis of preventing central sensitization, preventive analgesia is
      increasingly common. New opioids are being developed with minimization of adverse
      effects of traditional opioids. More intravenous nonopioid analgesics and
      adjuncts (such as dexmedetomidine and dexamethasone) are introduced for their
      opioid-sparing effects. Current evidence suggests that regional analgesic
      techniques are effective in the reduction of pain and stay in the PACU. Being
      available alternatives to epidural analgesia, perineural techniques and
      infiltrative techniques including wound infiltration, transversus abdominis plane
      block, local infiltration analgesia, and intraperitoneal administration have
      played a more important role for their effectiveness and safety.

PMID- 29180896
TI  - Checkpoint blockade in solid tumors and B-cell malignancies, with special
      consideration of the role of CD200.
AB  - In the ontogeny of a normal immune response, a series of checkpoints must be
      overcome to ensure that unwanted and/or harmful self-directed activation
      responses are avoided. Many of the molecules now known to be active in this
      overseeing of the evolving immune activation cascade, contributing inhibitory
      signals to dampen an overexuberant response, belong to the immunoglobulin
      supergene family. These include members of the CD28/CTLA-4:B7.1/B7.2
      receptor/ligand family, PD-1 and PDL-1, CD200 and CD200R, and the more recently
      described V-domain immunoglobulin suppressor of T-cell activation and its ligand
      (VSIG-3/IGSF11). Unfortunately, from the point of view of improving
      immunotargeting of cancer cells, triggering these checkpoint inhibitory signaling
      pathways, so necessary to maintain self-tolerance, simultaneously acts to prevent
      effective tumor immunity. The recent development of reagents, predominantly
      antibodies, to act as checkpoint blockade agents, has had a dramatic effect on
      human cancer treatment, with a marked reported success for anti-CTLA-4 and PD-1
      in particular in clinical trials. This review provides a general overview of the
      data now available showing the promise of such treatments to our cancer
      armamentarium and elaborates in depth on the potential promise of what can be
      regarded as an underappreciated target molecule for checkpoint blockade in
      chronic lymphocytic leukemia and solid tumors, CD200.

PMID- 29180897
TI  - Prognostic value of site-specific metastases and therapeutic roles of surgery for
      patients with metastatic bladder cancer: a population-based study.
AB  - Background: We aimed to evaluate the prognostic value of site-specific metastases
      in patients with metastatic bladder cancer and analyze the roles that surgeries
      play in the treatment of this malignancy. Materials and methods: A population
      based retrospective study using Surveillance, Epidemiology and End Results
      dataset was performed and metastatic bladder cancer patients were classified
      according to the sites of metastases (bone, brain, liver, lung and distant lymph
      nodes). Kaplan-Meier analysis with log-rank test was used for survival
      comparisons. Multivariate Cox regression model was employed to analyze the effect
      of distant metastatic sites on overall survival (OS) and cancer-specific survival
      (CSS). Results: A total of 1862 patients with metastatic bladder cancer from 2010
      to 2014 were identified. Bone, lung and distant lymph nodes were the most common
      metastatic sites. Patients with bone, brain, liver and lung involvement had worse
      OS and CSS compared to patients without the corresponding sites of metastases.
      Multivariate analysis showed that bone, brain, liver and lung metastases were
      independent prognostic factors for both OS and CSS, while distant node metastasis
      was not. Moreover, patients with a single metastatic site had more favorable OS
      (p<0.001) and CSS (p<0.001) than patients with multisite metastases. Among single
      site metastatic patients, distant nodes and liver metastases represented the best
      and the worst prognosis, respectively. Moreover, radical cystectomy was an
      independent predictor for better OS and CSS, while in patients with liver
      metastasis and multiple metastatic sites, RC did not bring benefits. Besides, in
      patients with a single metastatic site, metastasectomy seemed to be associated
      with favorable OS (p=0.042), especially for patients with age <65 years (p=0.006)
      and for muscle-invasive bladder cancer patients (p=0.031). Conclusion: Distant
      metastatic sites have differential impact on survival outcomes in patients with
      metastatic bladder cancer. Surgeries, including radical cystectomy and
      metastasectomy, might still lead to survival benefits for highly selected
      patients.

PMID- 29180898
TI  - Risk factors for hypocalcemia and hypoparathyroidism following thyroidectomy: a
      retrospective Chinese population study.
AB  - Background: Hypocalcemia is one of the most common postoperative complications
      following thyroid surgery in clinical practice. The occurrence of hypocalcemia is
      mainly attributed to hypoparathyroidism when parathyroid glands are
      devascularized, injured, or dissected during the surgery. The aim of this study
      was to analyze the risk factors for hypocalcemia and hypoparathyroidism following
      thyroidectomy. Patients and methods: A total of 278 patients who underwent
      thyroid surgery were analyzed retrospectively. Univariate analysis and
      multivariable logistic regression were performed to discover the risk factors for
      hypocalcemia and hypoparathyroidism. Results: Postoperative hypocalcemia occurred
      in 76 (27.3%) patients and hypoparathyroidism occurred in 42 (15.1%) patients.
      Seven factors were significantly related to the presence of postoperative
      hypocalcemia, namely, age (P=0.049), gender (P=0.015), lateral lymph node
      dissection (P=0.017), operation type (P<0.001), preoperative parathyroid hormone
      (PTH) level (P=0.035), operation time (P=0.001), and applying carbon
      nanoparticles (CNs; P=0.007). Our result revealed that gender (P=0.014), lateral
      lymph node dissection (P=0.038), operation type (P<0.001), operative time
      (P<0.001), and applying CNs (P=0.001) had a significant correlation with
      postoperative hypoparathyroidism. Conclusion: These findings were crucial for
      guiding surgeons to prevent the occurrence of hypocalcemia and
      hypoparathyroidism.

PMID- 29180899
TI  - Expression of minichromosome maintenance genes in renal cell carcinoma.
AB  - Minichromosome maintenance (MCM) proteins play an essential role in DNA
      replication. They have been shown to be overexpressed in various types of cancer.
      However, the role of this family in renal cell carcinoma (RCC) is widely unknown.
      In this study, we have identified a number of RCC datasets in the Gene Expression
      Omnibus database and also investigated the correlation between the expression
      levels of MCM genes and clinicopathological parameters. We found that the
      expression levels of MCM genes are positively correlated with one another.
      Expression levels of MCM2, MCM5, MCM6, and MCM7, but not of MCM3 and MCM4, were
      higher in RCC compared to paired adjacent normal tissue. Only the expression
      level of MCM4, but not of other MCMs, was positively correlated with tumor grade.
      In addition, a high-level expression of MCM2 in either primary tumor or
      metastases of RCC predicted a shorter disease-free survival time, while a high
      level expression of MCM4 or MCM6 in primary tumor was also associated with poorer
      disease-free survival. Interestingly, we also demonstrated that patients with
      their primary RCC overexpressing 2 or more MCM genes had a shorter disease-free
      survival time, while those with RCC metastases overexpressing 3 or more MCM genes
      had a shorter disease-free survival. Importantly, we also demonstrated that
      overexpression of MCM genes is an independent predictor for survival in RCC
      patients. Our results suggest that MCM2-7 genes may be an important prognostic
      marker for patients with RCC.

PMID- 29180900
TI  - Association between unilateral or bilateral mastectomy and breast cancer death in
      patients with unilateral ductal carcinoma.
AB  - Background: Utilization of bilateral mastectomy for unilateral breast cancer is
      increasing despite cost and surgical risks with conflicting reports of survival
      benefit. Current studies evaluating death after bilateral mastectomy have
      included patients treated both with breast conservation therapy and unilateral
      mastectomy. In this study, we directly compared breast cancer-specific death of
      patients who underwent bilateral or unilateral mastectomy for unilateral breast
      cancer using a matched cohort analysis. Methods: This was an observational study
      of women diagnosed with unilateral breast cancer from 1998 through 2002, using
      the Surveillance, Epidemiology, and End Results (SEER) database. A 4-to-1 matched
      cohort of patients was selected including 14,075 patients. Mortality of the
      groups was compared using Cox proportional hazards models for cause-specific
      death. Results: A total of 41,510 patients diagnosed with unilateral breast
      cancer were included. Unilateral mastectomy was performed in 93% of patients,
      while bilateral mastectomy was performed in the remaining 7% of patients. When 4
      to-1 matching was performed, 11,260 unilateral mastectomy and 2,815 bilateral
      mastectomy patients were included. Patients with bilateral mastectomy did not
      have a significantly lower hazard of breast cancer-specific death when compared
      with patients with unilateral mastectomy (hazard ratio: 0.92 vs 1.00, p=0.11).
      Conclusion: Bilateral mastectomy did not provide a clinically or statistically
      significant breast cancer-specific mortality benefit over unilateral mastectomy
      based on a matched cohort analysis of a nationwide population database. These
      findings should be interpreted in the context of patient preference and
      alternative benefits of bilateral mastectomy.

PMID- 29180901
TI  - Enhanced recovery programs in lung cancer surgery: systematic review and meta
      analysis of randomized controlled trials.
AB  - Background: Enhanced recovery after surgery (ERAS) program is an effective
      evidence-based multidisciplinary protocol of perioperative care, but its roles in
      thoracic surgery remain unclear. This systematic review of randomized controlled
      trials (RCTs) aims to investigate the efficacy and safety of the ERAS programs
      for lung cancer surgery. Materials and methods: We searched the PubMed and EMBASE
      databases to identify the RCTs that implemented an ERAS program encompassing more
      than four care elements within at least two phases of perioperative care in lung
      cancer surgery. The heterogeneity levels between studies were estimated by the
      Cochrane Collaborations. A qualitative review was performed if considerable
      heterogeneity was revealed. Relative risk (RR) and weighted mean difference
      served as the summarized statistics for the meta-analyses. Additional analyses
      were also performed to perceive potential bias risks. Results: A total of seven
      RCTs enrolling 486 patients were included. The meta-analysis indicated that the
      ERAS group patients had significantly lower morbidity rates (RR=0.64; p<0.001),
      especially the rates of pulmonary (RR=0.43; p<0.001) and surgical complications
      (RR=0.46; p=0.010), than those of control group patients. No significant
      reduction was found in the in-hospital mortality (RR=0.70; p=0.58) or
      cardiovascular complications (RR=1.46; p=0.25). In the qualitative review, most
      of the evidence reported significantly shortened length of hospital and intensive
      care unit stay and decreased hospitalization costs in the ERAS-treated patients.
      No significant publication bias was detected in the meta-analyses. Conclusion:
      Our review demonstrates that the implementation of an ERAS program for lung
      cancer surgery can effectively accelerate postoperative recovery and save
      hospitalization costs without compromising patients' safety. A worldwide
      consensus guideline is urgently required to standardize the ERAS protocols for
      elective lung resections in the future.

PMID- 29180902
TI  - Validation of algorithms to determine incidence of Hirschsprung disease in
      Ontario, Canada: a population-based study using health administrative data.
AB  - Objective: Incidence rates of Hirschsprung disease (HD) vary by geographical
      region, yet no recent population-based estimate exists for Canada. The objective
      of our study was to validate and use health administrative data from Ontario,
      Canada to describe trends in incidence of HD between 1991 and 2013. Study design:
      To identify children with HD we tested algorithms consisting of a combination of
      diagnostic, procedural, and intervention codes against the reference standard of
      abstracted clinical charts from a tertiary pediatric hospital. The algorithm with
      the highest positive predictive value (PPV) that could maintain high sensitivity
      was applied to health administrative data from April 31, 1991 to March 31, 2014
      (fiscal years 1991-2013) to determine annual incidence. Temporal trends were
      evaluated using Poisson regression, controlling for sex as a covariate. Results:
      The selected algorithm was highly sensitive (93.5%) and specific (>99.9%) with
      excellent predictive abilities (PPV 89.6% and negative predictive value >99.9%).
      Using the algorithm, a total of 679 patients diagnosed with HD were identified in
      Ontario between 1991 and 2013. The overall incidence during this time was 2.05
      per 10,000 live births (or 1 in 4,868 live births). The incidence did not change
      significantly over time (odds ratio 0.998, 95% confidence interval 0.983-1.013, p
      = 0.80). Conclusion: Ontario health administrative data can be used to accurately
      identify cases of HD and describe trends in incidence. There has not been a
      significant change in HD incidence over time in Ontario between 1991 and 2013.

PMID- 29180903
TI  - Prescription duration and treatment episodes in oral glucocorticoid users:
      application of the parametric waiting time distribution.
AB  - Purpose: Glucocorticoids are widely used medications. In many
      pharmacoepidemiological studies, duration of individual prescriptions and
      definition of treatment episodes are important issues. However, many data sources
      lack this information. We aimed to estimate duration of individual prescriptions
      for oral glucocorticoids and to describe continuous treatment episodes using the
      parametric waiting time distribution. Methods: We used Danish nationwide
      registries to identify all prescriptions for oral glucocorticoids during 1996
      2014. We applied the parametric waiting time distribution to estimate duration of
      individual prescriptions each year by estimating the 80th, 90th, 95th and 99th
      percentiles for the interarrival distribution. These corresponded to the time
      since last prescription during which 80%, 90%, 95% and 99% of users presented a
      new prescription for redemption. We used the Kaplan-Meier survival function to
      estimate length of first continuous treatment episodes by assigning estimated
      prescription duration to each prescription and thereby create treatment episodes
      from overlapping prescriptions. Results: We identified 5,691,985 prescriptions
      issued to 854,429 individuals of whom 351,202 (41%) only redeemed 1 prescription
      in the whole study period. The 80th percentile for prescription duration ranged
      from 87 to 120 days, the 90th percentile from 116 to 150 days, the 95th
      percentile from 147 to 181 days, and the 99th percentile from 228 to 259 days
      during 1996-2014. Based on the 80th, 90th, 95th and 99th percentiles of
      prescription duration, the median length of continuous treatment was 113, 141,
      170 and 243 days, respectively. Conclusion: Our method and results may provide an
      important framework for future pharmacoepidemiological studies. The choice of
      which percentile of the interarrival distribution to apply as prescription
      duration has an impact on the level of misclassification. Use of the 80th
      percentile provides a measure of drug exposure that is specific, while the 99th
      percentile provides a sensitive measure.

PMID- 29180904
TI  - Quality of oral surgery referrals and how to improve them.
AB  - Aim: To assess the quality of routine oral surgery referrals received at Halmstad
      Hospital and Vaxjo Hospital and to emphasize areas for improvement. Method: A
      retrospective study was performed on all routine oral surgery referrals received
      between 2014 and 2015 at both Halmstad Hospital and Vaxjo Hospital. A total of
      1,891 referral letters were assessed for their quality against a predetermined
      checklist of basic requirements of a satisfactory referral. The referrals were
      also categorized according to if it was sent by a male, female, private dental
      service, or the Swedish Public Dental Health service. Results: A diagnosis was
      missing in 30% of all referrals. Radiographs and information about previous
      radiographic examinations were not included in 10% of the referrals. Of those
      referrals that included radiographs, only around half were deemed adequate for
      diagnostic purposes. The presenting complaint was missing in 40% of all
      referrals. Current medical history was absent in 40% and current medication was
      omitted in 60% of the referrals. Information about tobacco use was only included
      in 10% of all referrals. Overall, female referrers performed better than male
      colleagues. Private referrals more regularly included information about
      diagnosis, previous treatment, and current medication. On the other hand,
      referrals from the public dental health service more frequently included
      radiographs, tobacco use, and current medical history. Conclusion: There is
      plenty of room for improving the standards of oral surgery referrals. We suggest
      that future electronic referral systems should only allow for submission once all
      of the essential information has been considered.

PMID- 29180905
TI  - Effects of minodronate in postmenopausal women with osteoporosis who received
      prior treatment with raloxifene.
AB  - Background: In clinical practice, patients with postmenopausal osteoporosis have
      often shown a poor response to treatment with an antiresorptive agent for several
      years. The purpose of this study was to investigate the efficacy of switching
      raloxifene with minodronate in patients who responded poorly to the treatment of
      postmenopausal osteoporosis with raloxifene. Patients and methods: This
      observational study was conducted based on a single-arm, non-randomized, open
      label design and was approved by the institute's institutional review board.
      Postmenopausal women with osteoporosis who became unresponsive in terms of bone
      mineral density (BMD) after being administered raloxifene for two or more years
      were enrolled. Patients were treated with 1 mg minodronate daily or 50 mg
      minodronate monthly. Changes in BMD and serum bone turnover markers were
      monitored at baseline, 6, 12, and 24 months after switching treatment. Results:
      Twenty-seven patients were enrolled. Two discontinued treatment because of
      adverse events related to the study drug. Among the remaining 25 patients, lumbar
      BMD significantly increased by 3.67%, 5.08%, and 6.97% at 6, 12, and 24 months,
      respectively, and femoral neck BMD increased by 1.63%, 2.18%, and 3.85% at 6, 12,
      and 24 months, respectively. Serum bone-specific alkaline phosphatase showed a
      significant reduction of 30.35% from the baseline (p<0.0001) within the first 6
      months, suggesting a stronger antiresorptive effect of minodronate. Serum N
      terminal telopeptide of type I collagen showed a tendency to decrease.
      Conclusion: Switching raloxifene with minodronate is effective in poor responders
      of osteoporosis treatment and should be considered as one of the treatment
      options for osteoporosis.

PMID- 29180906
TI  - Perceived acceptability of progesterone to prevent preterm births and low birth
      weight among HIV-infected and HIV-uninfected Zambian pregnant women.
AB  - Introduction: Intramuscular and vaginal progesterone are recommended for
      prevention of preterm labor (PTL) in women with risk factors. Studies are
      emerging to indicate that HIV-infected women on combination antiretroviral
      therapy (cART) are at risk of PTL and low birth weight (LBW), and may benefit
      from supplemental progesterone. This study aims to determine the perceived
      acceptability of various modes of progesterone supplementation to prevent PTL and
      LBW in HIV-infected and HIV-uninfected women. Methods: HIV-infected and HIV
      uninfected women were recruited in Lusaka, Zambia. The participants completed a
      questionnaire to assess their willingness to take oral, vaginal, or intramuscular
      progesterone supplementation for preventing PTL and LBW, preferred modes of
      supplementation, and concern for PTL and LBW. Results: The study questionnaire
      was completed by 147 participants. Of the participants, 98.6% would consider
      using a medication to help prevent PTL and LBW, of whom 97.9% would consider
      using an oral form of progesterone. In addition, 83.3% and 84.0% of women would
      consider intramuscular and vaginal (gel or tablet) administration of progesterone
      respectively. Between intramuscular and vaginal modes of progesterone, 60.5% of
      participants (n=147) preferred intramuscular progesterone, while 39.5% preferred
      vaginal progesterone. There was no difference in preference between HIV-infected
      (n=70) and HIV-uninfected (n=77) women. Conclusions/implications: Pregnant
      Zambian women demonstrated a high degree of acceptance for all modes of
      progesterone supplementation for the prevention of PTL and LBW. Women preferred
      intramuscular over vaginal supplementation. Progesterone supplementation can be
      considered a feasible intervention for preventing PTL and LBW in both HIV
      infected and HIV-uninfected pregnant Zambian women.

PMID- 29180907
TI  - Clinical behavior of a cohort of adult women with facial acne treated with
      combined oral contraceptive: ethinylestradiol 20 ug/dienogest 2 mg.
AB  - Acne vulgaris is the most common skin disease. It affects the young adult female
      population and generates great impact on physical and mental health. One of the
      treatments with good results for affected women is combined oral contraceptive
      pills (COCPs). The aim of this study was to determine the clinical effect of
      facial acne management with ethinylestradiol 20 ug/dienogest 2 mg in a cohort of
      Colombian adult women. A cohort of 120 female university students was followed
      for 12 months. These participants were enrolled in the Sexual and Reproductive
      Health Program of the Santiago de Cali University. This cohort admitted women
      between 18 and 30 years old who had chosen to start birth control with
      ethinylestradiol 20 ug/dienogest 2 mg COCPs, did not have contraindi cations to
      the use of COCPs, and had been diagnosed with acne. Monthly monitoring of facial
      acne lesion count was performed. Relative changes in facial lesion count were
      identified. At the end of follow-up, the percentage of reduction of lesions was
      94% and 23% of women had a 100% reduction in acne lesions. In conclusion, the
      continued use of the ethinylestradiol 20 ug/dienogest 2 mg COCPs reduced
      inflammatory and non-inflammatory acne lesions in reproductive-age women between
      18 and 30 years of age with no severe acne.

PMID- 29180908
TI  - Chronic low-grade postoperative endophthalmitis in a child with Marfan syndrome.
AB  - This case report describes a 9-year-old male who presented to the emergency
      department with 2 days' history of left painful red eye. On initial examination,
      his outside medical records indicated that he had bilateral subluxated lenses and
      had undergone left eye lensectomy with glued intrascleral fixation of an
      intraocular lens 8 weeks earlier. Vision in left eye was poor from first
      postoperative day but with no undue pain or redness, and poor vision was
      attributed to possible vitreous bleed. Subsequent postoperative course was
      uneventful. He was discharged from ophthalmic care on topical steroids and
      antibiotic drops, one week postsurgery. The eye was healing well until he
      developed pain, for which ophthalmic care was sought. He underwent anterior
      chamber tap with intravitreal injections. Aqueous samples were positive for
      Staphylococcus aureus DNA by polymerase chain reaction. Post vitrectomy and
      implant removal, his recovery was good and vision improved to 0.50 LogMar with
      aphakic correction.

PMID- 29180909
TI  - Wearable cardioverter defibrillators for the prevention of sudden cardiac arrest:
      a health technology assessment and patient focus group study.
AB  - Aim: To summarize the evidence on clinical effectiveness and safety of wearable
      cardioverter defibrillator (WCD) therapy for primary and secondary prevention of
      sudden cardiac arrest in patients at risk. Methods: We performed a systematic
      literature search in databases including MEDLINE via OVID, Embase, the Cochrane
      Library, and CRD (DARE, NHS-EED, HTA). The evidence obtained was summarized
      according to GRADE methodology. A health technology assessment (HTA) was
      conducted using the HTA Core Model(r) for rapid relative effectiveness
      assessment. Primary outcomes for the clinical effectiveness domain were all-cause
      and disease-specific mortality. Outcomes for the safety domain were adverse
      events (AEs) and serious adverse events (SAEs). A focus group with cardiac
      disease patients was conducted to evaluate ethical, organizational, patient,
      social, and legal aspects of the WCD use. Results: No randomized- or non
      randomized controlled trials were identified. Non-comparative studies (n=5)
      reported AEs including skin rash/itching (6%), false alarms (14%), and
      palpitations/light-headedness/fainting (9%) and discontinuation due to
      comfort/lifestyle issues (16-22%), and SAEs including inappropriate shocks (0
      2%), unsuccessful shocks (0-0.7%), and death (0-0.3%). The focus group results
      reported that experiencing a sense of security is crucial to patients and that
      the WCD is not considered an option for weeks or even months due to expected
      restrictions in living a "normal" life. Conclusion: The WCD appears to be
      relatively safe for short-to-medium term, but the quality of existing evidence is
      very low. AEs and SAEs need to be more appropriately reported in order to further
      evaluate the safety of the device. High-quality comparative evidence and well
      described disease groups are required to assess the effectiveness of the WCD and
      to determine which patient groups may benefit most from the intervention.

PMID- 29180910
TI  - Research during medical school: is it particularly difficult in developing
      countries compared to developed countries?
AB  - Objectives: Medical student involvement in research has been declining over the
      years. We reviewed the factors that hinder participation in research with a focus
      on developing countries. Methods: Literature search was performed using PubMed,
      MEDLINE and Cochrane Library. Peer-reviewed articles published between 1995 and
      2017 were screened for relevance to identify key factors affecting medical
      student involvement in research with a particular focus on developing world.
      Analytical review is presented here in this article in relation to commonly
      reported aspects related to research during medical school. Results: This search
      revealed varied contributing factors that hinder students' growth and interest in
      research. It commonly highlighted few aspects in relation to research during
      medical school, and they were "variability in research uptake among students and
      issues related to them, their knowledge and attitude toward research and
      organizational input and its influence on students". Conclusion: While early
      introduction to research by inculcating a mindset aimed at research has been
      proposed, it has not been seen in practice during either the medical school or
      beyond to an extent that was expected. It appears that developing countries,
      while they share some of the reasons with developed countries, have their own set
      of difficulties, which are influenced by culture, beliefs and priorities.

PMID- 29180911
TI  - Burning Mouth Syndrome: Aetiopathogenesis and Principles of Management.
AB  - Burning mouth syndrome (BMS) is a chronic debilitating oral condition
      characterised by a burning sensation of the oral mucosa in an otherwise
      apparently normal person. Its aetiology and pathogenesis are obscure, but both
      psychogenic factors and peripheral and central neuropathies appear to be
      implicated. There is no cure for BMS, and treatment with either local or systemic
      medications focuses on the relief of symptoms and on improving quality of life.
      In recalcitrant cases, psychological/psychiatric intervention may be helpful. In
      order to improve treatment outcomes, a better understanding of the pathogenesis
      of this syndrome might provide a basis for the development of more effective
      management strategies. In this short review, we discuss current knowledge of the
      diagnosis, aetiopathogenesis, and management of BMS.

PMID- 29180912
TI  - Dealing with the positive publication bias: Why you should really publish your
      negative results.
AB  - Studies with positive results are greatly more represented in literature than
      studies with negative results, producing so-called publication bias. This review
      aims to discuss occurring problems around negative results and to emphasize the
      importance of reporting negative results. Underreporting of negative results
      introduces bias into meta-analysis, which consequently misinforms researchers,
      doctors and policymakers. More resources are potentially wasted on already
      disputed research that remains unpublished and therefore unavailable to the
      scientific community. Ethical obligations need to be considered when reporting
      results of studies on human subjects as people have exposed themselves to risk
      with the assurance that the study is performed to benefit others. Some studies
      disprove the common conception that journal editors preferably publish positive
      findings, which are considered as more citable. Therefore, all stakeholders, but
      especially researchers, need to be conscious of disseminating negative and
      positive findings alike.

PMID- 29180913
TI  - Minimum requirements for the estimation of measurement uncertainty:
      Recommendations of the joint Working group for uncertainty of measurement of the
      CSMBLM and CCMB.
AB  - The International vocabulary of metrology - Basic and general concepts and
      associated terms (VIM3, 2.26 measurement uncertainty, JCGM 200:2012) defines
      uncertainty of measurement as a non-negative parameter characterizing the
      dispersion of the quantity values being attributed to a measurand, based on the
      information obtained from performing the measurement. Clinical Laboratory
      Standards Institute (CLSI) has published a very detailed guideline with a
      description of sources contributing to measurement uncertainty as well as
      different approaches for the calculation (Expression of measurement uncertainty
      in laboratory medicine; Approved Guideline, CLSI C51-A 2012). Many other national
      and international recommendations and original scientific papers about
      measurement uncertainty estimation have been published. In Croatia, the
      estimation of measurement uncertainty is obligatory for accredited medical
      laboratories. However, since national recommendations are currently not
      available, each of these laboratories uses a different approach in measurement
      uncertainty estimation. The main purpose of this document is to describe the
      minimal requirements for measurement uncertainty estimation. In such way, it will
      contribute to the harmonization of measurement uncertainty estimation, evaluation
      and reporting across laboratories in Croatia. This recommendation is issued by
      the joint Working group for uncertainty of measurement of the Croatian Society
      for Medical Biochemistry and Laboratory Medicine and Croatian Chamber of Medical
      Biochemists. The document is based mainly on the recommendations of Australasian
      Association of Clinical Biochemists (AACB) Uncertainty of Measurement Working
      Group and is intended for all medical biochemistry laboratories in Croatia.

PMID- 29180916
TI  - Measurement uncertainty of blood ethanol concentration in drink-driving cases in
      an emergency laboratory.
AB  - Introduction: The quality of blood ethanol concentration (BEC) determination is
      important because of its legal ramifications. Measurement uncertainty provides
      quantitative information about the quality and reliability of test results. In
      this study, we aim to calculate the measurement uncertainty for the ethanol test
      in our laboratory measured with a Synchron Systems Ethanol assay kit by employing
      an enzymatic rate method on the Beckman-Coulter Olympus AU400 auto analyzer
      (Beckman Coulter Inc, Melville, USA). Materials and methods: The measurement
      uncertainty values were calculated in accordance to the Nordtest guidelines. All
      vehicle drivers involved in a traffic accident were retrospectively inspected for
      the BEC test conducted during July to December 2016 in our emergency laboratory.
      Results: A 1034 vehicle drivers had their BEC tested. The results for 181 drivers
      were > 0.50 g/L and reported as positive. The serum ethanol concentration in
      those showing a positive result was 2.04 +/- 1.01 g/L, over four times the legal
      limit. The median BEC in those showing a negative result was 0.03 (IQR: 0.03)
      g/L. The expanded uncertainty obtained was 19.74%. When measurement uncertainty
      values were added to the results of the 1034 drivers who were retrospectively
      screened, eight vehicle drivers had results with 95% confidence intervals that
      exceeded the legal limit 0.50 g/L. Conclusions: The BEC test results for vehicle
      drivers with values close to legal limits should be reported as the obtained
      ethanol concentration with corresponding measurement uncertainty.

PMID- 29180915
TI  - National survey on current situation of critical value reporting in 973
      laboratories in China.
AB  - Introduction: The aim of the study was to investigate the state-of-the-art of the
      performance of critical value reporting and provide recommendations for
      laboratories setting critical value reporting time frames. Materials and methods:
      The National Centre for Clinical Laboratories in China initiated a critical value
      reporting investigation in 2015. A questionnaire related to critical value
      reporting policy was sent to 1589 clinical laboratories in China online. The
      questionnaire consisted of a set of questions related to critical value reporting
      policy and a set of questions related to timeliness of critical value reporting.
      The survey data were collected between March and April 2015. Results: A total
      survey response rate was 61.2%. The critical value unreported rate, unreported
      timely rate, and clinical unacknowledged rate of more than half of participants
      were all 0.0%. More than 75.0% of participants could report half of critical
      values to clinicians within 20 minutes and could report 90.0% of critical values
      to clinicians within 25 minutes (from result validation to result communication
      to the clinician). The median of target critical value reporting time was 15
      minutes. "Reporting omission caused by laboratory staff", "communications
      equipment failure to connect", and "uncompleted application form without contact
      information of clinician" were the three major reasons for unreported critical
      value. Conclusions: The majority of laboratories can report critical values to
      responsible clinical staff within 25 minutes. Thus, this value could be
      recommended as suitable critical value reporting time frame for biochemistry
      laboratories in China. However, careful monitoring of the complete reporting
      process and improvement of information systems should ensure further improvement
      of critical value reporting timeliness.

PMID- 29180914
TI  - Insights into cerumen and application in diagnostics: past, present and future
      prospective.
AB  - Cerumen or earwax is an emerging bio-fluid in clinical diagnosis that has been
      very little exploited during the past decades in spite of its high diagnostic
      potential. It is highly abundant in diagnostic biomarkers such as genetic
      material, lipids, proteins, chemical elements, internal and external metabolites
      (e.g. hormones, volatile organic compounds, amino acids, xenobiotics etc.)
      reaching earwax from the blood circulation. Thus, it is able to reflect not only
      physiology, pathophysiology of the human body but can also detect recent and long
      term exposure to environmental pollutants, without the need of invasive blood
      tests and in the same time overcoming many disadvantages faced by using other
      diagnostic biological fluids. This review discusses the biology, functions,
      chemistry of earwax, past and current approaches for the study of its chemical
      composition, emphasizing how a detected variation in its composition can offer
      information of high clinical value, which can be useful in diagnosis of many
      diseases such as metabolic disorders and tumours as well as in forensic
      applications. It also presents details about techniques of sample collection,
      storage, and analysis. Moreover, it highlights concerns about the use of earwax
      for diagnostic purposes, which should be addressed to make earwax diagnostics a
      reality in the future.

PMID- 29180917
TI  - Establishing the upper reference limit of Galectin-3 in healthy blood donors.
AB  - Introduction: Galectin-3 (Gal-3) is an independent predictor of poor outcomes and
      mortality in patients with heart failure (HF). Thus, it has been proposed as a
      reliable prognostic biomarker for HF. The definition of reference intervals is
      mandatory for interpreting the findings of experimental studies and encouraging
      the routine use of biomarkers in clinical practice. To date, no study assessed
      the reference intervals of Gal-3 and identified the biological variables that
      affect its concentration in a well-defined healthy population. The aim of this
      study was to determine the upper reference limit (URL) of Gal-3 in a highly
      reliable population of healthy subjects. Materials and methods: We recruited 714
      blood donors. After measuring surrogate biomarkers to identify underlying
      diseases, 8 subjects were excluded. A final population of 706 individuals (385
      men (54.5%); median age 39 (18-65) years) was included. The URL was calculated
      using the non-parametric percentile approach. Results: The 97.5th percentile URL
      of plasma Gal-3 in our study population (90% CI) was 26.1 (23.3-31.5) ng/mL.
      After stratifying subjects according to age, the URL of Gal-3 was found to be
      considerably higher in older (> 45 years) than in younger subjects (31.5 (26.2
      51.4) vs 21.8 (21-26.1) ng/mL, respectively). No sex-related differences were
      found in Gal-3 plasma concentration. Conclusions: We established the URL of Gal-3
      in a highly selected healthy population. Our findings indicate that age is an
      important determinant of Gal-3 plasma concentration, so that multiple diagnostic
      cut-offs should be preferably used according to the different age classes.

PMID- 29180918
TI  - Analytical evaluation of a fully automated immunoassay for faecal calprotectin in
      a paediatric setting.
AB  - Introduction: Faecal calprotectin (FC) is a routinely used marker for identifying
      and monitoring children with inflammatory bowel disease (IBD). This non-invasive
      test is useful for screening children with gastrointestinal symptoms to avoid
      unnecessary invasive procedures. In this study, we validated for the first time
      the performance of a fully automated particle-enhanced turbidimetric immunoassay
      (PETIA) on the VITROS(r) 5600 analyzer for measurement of FC in symptomatic
      children and adolescents. Materials and methods: For performance validation of
      the PETIA (fCAL(r) turbo, Buhlmann Laboratories, Switzerland) on the VITROS(r)
      5600 analyzer (Ortho Clinical Diagnostics, USA) limit of quantitation (LoQ),
      linearity, precision data and calibration curve stability were defined.
      Additionally, 95 faecal samples were measured using the PETIA, an enzyme-linked
      immunosorbent assay (ELISA; fCAL(r), Buhlmann Laboratories, Switzerland) and a
      semi-quantitative lateral flow assay (Quantum Blue Reader(r), Buhlmann
      Laboratories, Switzerland) for agreement evaluation. Results: The LoQ for
      calprotectin using PETIA on the VITROS(r) 5600 analyzer was 21 ug/g. The
      linearity range was 20 - 2100 ug/g and the precision study showed a total
      coefficient of variation (CV) between 2.3% and 8.9%. The calibration curve was
      stable for 4 weeks. Using the clinical samples quantifiable by PETIA, ELISA and
      the semi-quantitative lateral flow assay, Passing-Bablok regression analysis and
      Bland-Altman plots showed good agreement. Conclusions: Due to good performance
      characteristics and agreement with established methods, the fully automated PETIA
      on the routine chemistry analyzer VITROS(r) 5600 is a new analytical option for
      the rapid determination of FC.

PMID- 29180919
TI  - False positive immunoassay for heparin-induced thrombocytopenia in the presence
      of monoclonal gammopathy: a case report.
AB  - Heparin induced thrombocytopenia (HIT) is a life-threatening disorder which
      diagnosis depends on laboratory evaluation. The objective of this report is to
      present the impact of different laboratory methods for HIT detection on the
      diagnostic evaluation process. In this case, a 78-year old female patient
      previously diagnosed with monoclonal gammopathy of undetermined significance
      (MGUS) was administered with heparin for pulmonary embolism treatment. Patient's
      initial diagnostic work-up (determination of platelet count and prothrombin time
      measurement for monitoring of pharmacotherapy) was followed by the clinical
      estimation of HIT likelihood by "4Ts" score, two immunoassays (ID-PaGIA
      Heparin/PF4 Antibody Test and ELISA PF4 IgG assay) and one functional test called
      high-performance liquid chromatography serotonin release assay (HPLC-SRA). The
      result of "4Ts" score indicated a low likelihood of HIT but persistent
      thrombocytopenia that appeared days after discontinuation of heparin therapy
      suggested delayed-onset HIT. Both immunoassays were positive for presence of HIT
      autoantibodies, while the functional HPLC-SRA was negative. Since different
      methods gave opposing results, their interpretation required great attention. In
      comparison to the HPLC-SRA, immunoassays are prone to the analytical
      interferences associated with the presence of non-specific antibodies, which may
      lead to false positive results. In this case, where the patient is known to
      produce antibodies of undetermined significance, HIT was ruled out as the
      possible cause of persistent thrombocytopenia primarily due to the negative
      result of HPLC-SRA, which is not prone to this type of interferences, but also
      due to the low "4Ts" clinical score.

PMID- 29180920
TI  - Urinary free cortisol assessment by liquid chromatography tandem mass
      spectrometry: a case study of ion suppression due to unacquainted administration
      of piperacillin.
AB  - Introduction: Liquid chromatography coupled to atmospheric pressure ionization
      tandem mass spectrometry (LC-ESI-MS/MS) is currently considered the reference
      method for quantitative determination of urinary free cortisol (UFC). One of the
      major drawbacks of this measurement is a particular form of matrix effect,
      conventionally known as ion suppression. Materials and methods: We describe here
      the case of a 66-year-old-patient referred to the daily service of general
      medicine for intravenous antibiotic administration due to a generalized
      Staphylococcus aureus infection and for routine 24 hours UFC monitoring in the
      setting of glucocorticoid replacement therapy. Results: The observation of 10
      fold decrease of internal standard of cortisol signal led us to hypothesize the
      presence of an ion suppression effect due to a co-eluting endogenous compound.
      Screening analysis of tandem mass spectrometry (MS/MS) spectra of the interfering
      molecule, along with in vitro confirmation analyses, were suggestive of the
      presence of high concentration of piperacillin. The problem was then easily
      solved with minor modifications of the chromatographic technique. Conclusions:
      According to our findings, antibiotic therapy with piperacillin/tazobactam should
      be regarded as an important interference in UFC assessment, which may potentially
      affect detection capability, precision and accuracy of this measurement. This
      case report emphasizes that accurate anamnesis and standardization of all phases
      of urine collection are essential aspects for preventing potential interference
      in laboratory testing.

PMID- 29180921
TI  - Erratum: Ethical issues in publishing in predatory journals.
AB  - [This corrects the article DOI: 10.11613/BM.2017.030.].

PMID- 29180922
TI  - Corrigendum to: Does small equal predatory? Analysis of publication charges and
      transparency of editorial policies in Croatian open access journals.
AB  - [This corrects the article DOI: 10.11613/BM.2017.032.].

PMID- 29180923
TI  - Corrigendum to: Impact of reference change value (RCV) based autoverification on
      turnaround time and physician satisfaction.
AB  - [This corrects the article DOI: 10.11613/BM.2017.037.].

PMID- 29180924
TI  - Immune checkpoints, their control by immunotherapy and ovarian cancer.
AB  - Immune checkpoints are new targets for manipulation of immunological control over
      malignant tumors. They provide an important means to manage especially recurrent
      and refractory cancers and those cancers where there is an unmet need such as
      recurrent melanoma, renal cell carcinoma and recurrent ovarian cancer. As a new
      development this subject is experiencing rapid progress and multiple avenues are
      opening up. However, there are many hurdles to overcome, requiring constant
      updating, especially for students of ovarian cancer, who are looking at it with
      much hope.

PMID- 29180925
TI  - Marjolin's ulcer in chronic wounds - review of available literature.
AB  - Marjolin's ulcer is a rare, aggressive skin cancer developing in scar tissue,
      chronic ulcers and areas affected by inflammations. Its incidence is estimated to
      range from 1% to 2% of all burn scars. It most frequently takes the form of
      squamous cell carcinoma which sometimes is diagnosed during examination of
      lesions developing in scars and hard-to-heal chronic wounds (pressure sores, leg
      ulcers). Therapeutic management of Marjolin's ulcer requires well-designed
      treatment plan to ensure optimal medical care and good quality of life for the
      patient. The high risk of metastases and damage to the structure of vitally
      important organs determines the need for early diagnosis and prompt surgical
      intervention with supplementary therapy. The purpose of the study was to examine
      etiopathogenesis of Marjolin's ulcer and principles of its treatment. The authors
      focused on the aspect of malignant degeneration in chronic wounds (leg ulcers,
      pressure sores) as a very rare, aggressive form of Marjolin's ulcer. A review of
      the available literature on the issue of Marjolin ulcers was conducted using the
      key words; Marjolin ulcers, pressure sore, chronic wound. Malignant degeneration
      in chronic wounds is a very rare aggressive form of Marjolin ulcer. Increased
      oncological alertness should be displayed by nursing and medical personnel taking
      care of patients with chronic wounds.

PMID- 29180926
TI  - Radiotherapy in testicular germ cell tumours - a literature review.
AB  - Testicular germ cell tumours (GCT) represent about 1-2% of malignant in men. The
      essential therapeutic option for early-stage GCT is radical orchiectomy (RO),
      except in situations that require immediate chemotherapy in patients with a
      massive dissemination and unequivocally elevated levels of tumour markers.
      Postoperative radiotherapy (PORT) in patients with testicular seminoma in
      Clinical Stage I (CS I) is one of the treatment options next to active
      surveillance (AS) and chemotherapy (CHTH). Regardless of the procedure, five-year
      survival in this group of patients ranges between 97% and 100%. In the article,
      we present the literature review pertinent to therapeutic options, with a focus
      on radiotherapy. We have searched MEDLINE (PubMed) for all studies on patients
      with GCT treated with radiation therapy during the last 20 years, and the current
      therapeutic recommendations. We used the following keywords: germ cell tumours,
      testis, seminoma, non-seminoma, radiotherapy, outcome.

PMID- 29180927
TI  - Comparative efficacy of epigallocatechin-3-gallate against H2O2-induced ROS in
      cervical cancer biopsies and HeLa cell lines.
AB  - Aim of the study: Antioxidants play an important role in maintaining
      physiological homeostasis. Recent literature emphasises the potential therapeutic
      effects of natural antioxidants that play anti-inflammatory and antioxidant
      effects applicable in preventing oxidative stress-induced injury, which
      characterises their pathogenesis. The goal of this study was to evaluate the
      protective role of EGCG on the HeLa cell line and cancerous cells. Material and
      methods: The HeLa cell line and cervical cancer biopsies (CCB) were treated with
      varying doses of antioxidants to determine their effects. Thereafter, hydrogen
      peroxide (0-10 nM) - an ROS-generating compound - was co-cultured with varying
      doses of epigallocatechin-3-gallate (EGCG). The effect of this compound on
      superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity was
      assessed. Result: The activity of SOD and GPx was protected significantly in the
      treatment of EGCG in cervical cancer biopsies and HeLa cell line. Hypothesis: It
      is hypothesised that EGCG has free radical scavenging properties. Conclusions:
      EGCG protected the activity SOD and GPx equally in cervical cancer biopsies (CCB)
      and HeLa cell line.

PMID- 29180928
TI  - The importance of serum and pleural fluid level of vascular endothelial growth
      factor (VEGF) and VEGF fluid/serum ratio in the differential diagnosis of
      malignant mesothelioma-related pleural effusion.
AB  - Aim of the study: Vascular endothelial growth factor (VEGF) is one of the
      parameters that has been studied in differential diagnosis of malignant fluids.
      This study is aimed at evaluate applicability of serum, fluid VEGF level and
      fluid to serum VEGF ratio in the diagnosis of malignant pleural mesothelioma
      (MPM). Material and methods: The patients with pleural effusion over age of 18,
      between 2011 and 2015 were included in the study. They were divided into three
      groups: group 1 - mesothelioma patients; group 2 - other malignancies; and group
      3 - benign aetiologies. Group 1 and 2 were termed as the malignant group. Fluid,
      serum VEGF levels, and the ratio of fluid/serum VEGF level were studied to
      evaluate the fluid/serum VEGF ratio in all groups. Results: Twenty cases with
      mesothelioma, 44 cases with other malignancies, and 20 cases with benign
      aetiologies were included in this study. No statistically significant difference
      was found according to serum VEGF levels for all groups, (group 1: 437 +/-324
      pg/ml, group 2: 354 +/-223 pg/ml, group 3: 373 +/-217 pg/ml, p = 0.836), while
      fluid VEGF levels showed a statistically significant difference (group 1: 3359 +/
      700 pg/ml, group 2: 2175 +/-435 pg/ml, group 3: 1092 +/-435 pg/ml, p = 0.041).
      The ratio of fluid to serum VEGF levels showed a difference, at the significance
      limit, between the malignant (group 1 and group 2) and benign (group 3) groups
      (8.83 +/-1.29 vs. 4.57 +/-1.07, p = 0.059) but showed a statistically significant
      difference between the mesothelioma and benign groups (12.11 +/-1.68 vs. 4.57 +/
      1.07, p = 0.044). Conclusions: The VEGF fluid/serum ratio may be an applicable
      parameter in the differential diagnosis of malignant fluids, especially MPM.

PMID- 29180929
TI  - Estimation of the prevalence and distribution of HPV genotypes and identification
      of related risk factors among Turkish women.
AB  - Aim of the study: The present study aims to estimate the prevalence and
      distribution of HPV genotypes and identify related risk factors among Turkish
      women. Material and methods: 11 624 Turkish women attending our gynaecological
      clinic and expressing a desire for access to cervical cancer screening were
      assessed during the years 2014-2016. Cervical specimens were collected and
      transported using the HC2 HPV DNA Collection Device (consisting of a cervical
      brush and digene Specimen Transport Medium). Results: Among these 11 624
      individuals, positive HPV test results were obtained for 325 (2.79%), and
      negative results were observed for 11 299 (97.2%). The vast majority of patients
      were between the 3rd and 5th decades and the mean age of the patients was 44 +/
      9.12 (range 27-66). Among the HPV-positive women, 205 were positive for a single
      HPV type (205/325 = 63.1% of HPV infections; 205/11624 = 1.76% of all samples)
      and 120 were positive for multiple types (120/325 = 36.9% of HPV infections;
      120/11624 = 1.03% of all samples). The four most prevalent high-risk types were
      HPV 16, 31, 51 and 52, with frequencies of 11.25%, 7.83%, 6.06% and 3.16%,
      respectively. Conclusions: There appears to be geographic variation in the
      distribution of HPV genotypes. In this study, the four most prevalent high-risk
      types were HPV 16, 31, 51 and 52, with frequencies of 11.25%, 7.83%, 6.06% and
      3.16%, respectively.

PMID- 29180930
TI  - Examination of anastomotic leak with aqueous contrast swallow after total
      gastrectomy: Should it be carried out routinely?
AB  - Aim of the study: Examination of esophagojejunal (EJ) anastomosis with aqueous
      contrast swallow after total gastrectomy is still routinely conducted by many
      centres. The present study aimed to answer the question: Is it necessary to
      evaluate EJ anastomosis in terms of leakage by having every patient drink oral
      contrast agent before initiation of oral food intake after total gastrectomy (TG)
      performed due to gastric cancer? Material and methods: Clinical and radiological
      results of patients on whom total gastrectomy was performed due to gastric cancer
      between January 2013 and December 2016 were retrospectively reviewed. Diagnostic
      method used for patients in whom leak developed and therapeutic interventions
      were assessed. Evaluation results from aqueous contrast agent and clinical,
      laboratory, and tomographic findings were studied. Results: Sixty of the 69
      patients who underwent total gastrectomy with a diagnosis of gastric
      adenocarcinoma swallowed aqueous contrast agent on postoperative day 7 +/-2 days
      and were evaluated in terms of anastomotic leak. Leak developed in 14 patients
      (20.2 %), 10 of whom ingested contrast agent. Leak was identified in 6 of those
      patients; however, diagnosis was made with multislice computed tomography (CT) in
      four patients (40%). The sensitivity of the examination with aqueous contrast
      agent was 60%. Conclusions: Evaluating anastomotic leak with aqueous contrast
      agent after TG has low sensitivity, and it would be wise to resort to this
      procedure in cases with clinical suspicion, rather than routinely performing it
      in every patient.

PMID- 29180931
TI  - Treatment results of adult patients with primary bone tumours of the humerus with
      the use of the oncological modular endoprosthesis.
AB  - Aim of the study: Primary bone tumours are relatively rare, but their diagnosis
      and treatment is difficult and connected with a high risk of complications. The
      goal of this report is a retrospective evaluation of outcomes in patients with
      primary tumours of the humerus treated in our centre with the use of modular
      endoprosthetic reconstruction. Material and methods: Currently, surgical
      treatment is a standard procedure for local therapy, with wide tumour-free margin
      resection after a planned multidisciplinary and individualised strategy of tumour
      management based on the diagnostic biopsy result. The best option for patients to
      avoid disability is simultaneous surgical reconstruction aiming to spare the limb
      and its functionality. Results: In this report, we present the results of
      treatment of our 11 adult patients suffering from primary bone tumours of the
      humerus, who have undergone wide bone resection followed by reconstruction with
      the use of a modular MUTARS(r) endoprosthesis. Conclusions: The study showed that
      prosthetic reconstruction of the resected humerus due to a primary bone tumour is
      safe and acceptable for patients; despite the fact that limitation of active
      abduction of the shoulder is up to 20 grades, this surgical procedure provides
      satisfactory limb function.

PMID- 29180932
TI  - Assessment of the accuracy of dose calculation in the build-up region of the
      tangential field of the breast for a radiotherapy treatment planning system.
AB  - Aim of the study: Our objective was to quantify the accuracy of dose calculation
      in the build-up region of the tangential field of the breast for a TiGRT
      treatment planning system (TPS). Material and methods: Thermoluminescent
      dosimeter (TLD) chips were arranged in a RANDO phantom for the dose measurement.
      TiGRT TPS was also used for the dose calculation. Finally, confidence limit
      values were obtained to quantify the accuracy of the dose calculation of the TPS
      at the build-up region. Results: In the open field, for gantry angles of 15
      degrees , 30 degrees , and 60 degrees , the confidence limit values were 17.68,
      19.97, and 34.62 at a depth of 5 mm, and 24.01, 19.07, and 15.74 at a depth of 15
      mm, respectively. In the wedge field, for gantry angles of 15 degrees , 30
      degrees , and 60 degrees , the confidence limit values were 21.64, 26.80, and
      34.87 at a depth of 5 mm, and 27.92, 22.04, and 20.03 at a depth of 15 mm,
      respectively. Additionally, the findings showed that at a depth of 5 mm, the
      confidence limit values increased with increasing gantry angle while at a depth
      of 15 mm, the confidence limit values decreased with increasing gantry angle.
      Conclusions: Overall, TiGRT TPS overestimated doses compared to TLD measurements,
      and the confidence limit values were greater for the wedge field than for the
      open fields. Our findings suggest that the assessment of dose distributions in
      large-dose gradient regions (i.e. build-up region) should not entirely rely on
      TPS calculations.

PMID- 29180933
TI  - Implementation of an enhanced recovery after surgery (ERAS) protocol in a
      gynaecology department - the follow-up at 1 year.
AB  - Aim of the study: An ERAS protocol provides the latest perioperative care
      principles, whose primary aim is to reduce complication rates, and therefore
      mortality. The aim of this study is to establish the progress of the ERAS pathway
      implementation in our gynaecology department. Material and methods: This was a
      retrospective analysis of two sets of 100 consecutive medical records: patients
      treated before (PRE-ERAS) and after (ERAS) introduction of the ERAS protocol. All
      patients were comparable and all underwent major gynaecological surgery. Patients
      as well as medical and nursing staff were informed about the proposed
      preparation, surgical management and postoperative routine. Results and
      conclusions: Patients were given supper and drank water during the night.
      Laparoscopic surgery was used in 44% and spinal anaesthesia was given for open
      surgery in 43 study patients. Use of drains was reduced only by 23%, bowel
      preparation by 15%. Intravenous fluid administration was reduced by 22%. Use of
      postoperative morphine was minimised to 12 patients. Postoperative nausea was
      managed with the regular use of anti-emetics. Anti-coagulation was given to 80%
      of the study group. Difficulties in the introduction of the ERAS protocol were
      due to refusal by some patients to mobilise and eat early postoperatively.
      Patients in the ERAS programme group were discharged earlier.Further information
      about the ERAS protocol in the media would facilitate patients' education among
      conservative society. In order to introduce new and innovative treatment methods,
      one has to take into account the cultural and ideological factors, especially
      when patient involvement is essential.

PMID- 29180934
TI  - Long-term survival in a patient with unresectable liver metastases from uveal
      melanoma treated with transarterial chemoembolization with irinotecan eluting
      beads - case report and review of literature.
AB  - Introduction: Treatment of unresectable liver metastases (LM) from uveal melanoma
      (UM) remains a major clinical challenge. Systemic chemotherapy and
      chemoimmunotherapy regimens extrapolated from cutaneous melanoma are considered
      to be ineffective in therapy of metastases from uveal melanoma. Studies suggest
      that the progression of hepatic metastases rather than the primary tumor or
      metastases in other organs determines survival. Case report: We report a case of
      transarterial chemoembolization of 57-year-old man diagnosed with unresectable
      liver metastases from uveal melanoma with irinotecan eluting beads. Therapy
      resulted in long progression free survival and overall survival, 41 months and 45
      months after diagnosis of metastatic disease respectively. Patient did not
      experience any major side effects of the therapy. Follow-up CTs indicate stable
      disease in mRECIST criteria and partial response in CHOI criteria. Conclusions:
      Transarterial chemoembolization with drug eluting beads loaded with irinotecan
      may be an effective treatment of unresectable liver metastases from uveal
      melanoma.

PMID- 29180935
TI  - Atypical bilateral cerebellopontine angle medulloblastoma: differential
      diagnosis, immunohistochemical features and radiological presentation.
AB  - Medulloblastoma (MB) is a highly aggressive soft tissue neoplasm, classified as a
      primitive neuroectodermal tumor. It is the most common posterior fossa tumor in
      children, but occurs rarely in adults. MB accounts for approximately 20% of all
      primary central nervous system (CNS) tumors of childhood, while its incidence is
      around 1% of adult brain tumors. Most often it occurs in the cerebellum. We
      report a case of multicentric MB involving the bilateral cerebellopontine angle
      (CPA) and right cerebellar hemisphere. The tumor showed isointensity on T1/T2
      weighted images, and slight hyperintensity on T2-weighted fluid-attenuated
      inversion-recovery (FLAIR) images. The MB had restricted diffusion on diffusion
      weighted images (DWI). It was not easy to make an accurate diagnosis before
      biopsy. The lesion in our patient presented with atypical MR image features of
      medulloblastoma. To our knowledge, this is the first case of bilateral CPA MB.

PMID- 29180936
TI  - Osimertinib - effective treatment of NSCLC with activating EGFR mutations after
      progression on EGFR tyrosine kinase inhibitors.
AB  - Non-small cell lung cancer (NSCLC) driven by activating mutations in epidermal
      growth factor receptor (EGFR) constitutes up to 10% of NSCLC cases. According to
      the NCCN recommendations, all patients (with the exception of smoking patients
      with squamous cell lung cancer) should be screened for the presence of activating
      EGFR mutations, i.e. deletion in exon 19 or point mutation L858R in exon 21, in
      order to select the group that benefits from EGFR tyrosine kinase inhibitors
      (EGFR TKIs) treatment. Among approved agents there are the 1st generation
      reversible EGFR TKIs, erlotinib and gefitinib, and the 2nd generation
      irreversible EGFR TKI, afatinib. The objective response rates to these drugs in
      randomised clinical trials were in the range of 56-74%, and median time to
      progression 9-13 months. The most common determinant of resistance to these drugs
      is the clonal expansion of cancer cells with T790M mutation (Thr790Met) in exon
      20 of EGFR. Osimertinib (TagrissoTM), a 3rd generation, irreversible EGFR
      tyrosine kinase inhibitor, constitutes a novel, highly efficacious treatment for
      NSCLC patients progressing on EGFR TKIs with T790M mutation confirmed as the
      resistance mechanism. Resistance mutation can be determined in tissue or liquid
      biopsy obtained after progression on EGFR TKIs. Osimertinib has a favourable
      toxicity profile, with mild rash and diarrhoea being the most common. In this
      article, we present three cases that were successfully treated with osimertinib
      after progression on 1st and 2nd generation EGFR TKIs.

PMID- 29180937
TI  - Synthesis and Cytotoxic Evaluation of Steroidal Copper (Cu (II)) Complexes.
AB  - Using estrone and pregnenolone as starting materials, some steroidal copper
      complexes were synthesized by the condensation of steroidal ketones with
      thiosemicarbazide or diazanyl pyridine and then complexation of steroidal
      thiosemicarbazones or steroidal diazanyl pyridines with Cu (II). The complexes
      were characterized by IR, NMR, and HRMS. The synthesized compounds were screened
      for their cytotoxicity against HeLa, Bel-7404, and 293T cell lines in vitro. The
      results show that all steroidal copper (II) complexes display obvious
      antiproliferative activity against the tested cancer cells. The IC50 values of
      complexes 5 and 12 against Bel-7404 (human liver carcinoma) are 5.0 and 7.0 MUM.

PMID- 29180938
TI  - Erratum: High carotenoid production by a halotolerant bacterium, Kocuria sp.
      strain QWT-12 and anticancer activity of its carotenoid.
AB  - [This corrects the article on p. 840 in vol. 16, PMID: 28827999.].

PMID- 29180939
TI  - Transnational aging: toward a transnational perspective in old age research.

PMID- 29180940
TI  - National and transnational belonging among Turkish and Moroccan older migrants in
      the Netherlands: protective against loneliness?
AB  - This research investigates how a sense of belonging functions as protective
      mechanism against loneliness. Inspired by the work of Berry (1980) on
      acculturation strategies (i.e. integration, assimilation, separation and
      marginalization), we distinguish migrants who feel a relatively strong or weak
      sense of belonging to larger society and those who feel a strong or weak
      belonging to the "own group." We expect that more national belonging contributes
      to less loneliness. We add a transnational perspective by arguing that feelings
      of belonging to the own group can take place in the country of settlement, but
      can also be transnational, i.e. a feeling of belonging to the country of origin.
      Transnational belonging can protect against loneliness, as it acknowledges the
      importance of place attachment. Using data from the Longitudinal Aging Study
      Amsterdam on older migrants aged 55-66, we employ latent class analysis and find
      five national belonging clusters, interpretable in terms of Berry's acculturation
      strategies. Further analyses reveal mixed evidence: some aspects of transnational
      belonging vary with belonging to the own group, but other aspects point to a
      third dimension of belonging. Regression analysis shows that those marginalized
      are loneliest and that a transnational sense of belonging contributes to more
      loneliness. We conclude that Berry's (1980) typology is useful for interpreting
      older migrants' national belonging and that a transnational sense of belonging is
      apparent among older migrants, but needs to be explored further.

PMID- 29180941
TI  - Legislating for transnational ageing: a challenge to the logics of the welfare
      state.
AB  - Transnational ageing presents fundamental challenges to nationally bounded
      welfare states, which historically have tended to be organised according to a
      logic of solidarity among nationals and permanent residents of a given state
      territory. Nonetheless, the Dutch and French governments have taken steps to
      break this link between solidarity and territorially bounded consumption of
      welfare, by providing lifelong income security for older migrants who return to
      countries of origin on a permanent or semi-permanent basis. This article asks
      what motivated policymakers to initially develop these novel policy tools for
      transnational ageing which contradict the territorial logic of the welfare state.
      Based on interviews with key stakeholders and available official documents, we
      find that in both France and the Netherlands, policymakers' initial motivations
      can be characterised as rather benign, if not beneficent: to facilitate return
      for those who are willing but unable to afford it. However, two types of obstacle
      have impeded the delivery of such policies. Non-discrimination clauses and free
      movement rights in EU law may make it difficult to implement policies for
      specific categories of older migrants. Electoral realpolitik may also lead
      policymakers to shelve policies which benefit older migrants, in a European
      context where public opinion on immigration is less and less favourable.
      Nonetheless, opposition may be neutralised by the budgetary advantages of these
      schemes, since older returnees do not consume public services such as healthcare.

PMID- 29180942
TI  - The emergence of care facilities in Thailand for older German-speaking people:
      structural backgrounds and facility operators as transnational actors.
AB  - This paper presents findings from an ethnographic study of old age care
      facilities for German-speaking people in Thailand. It analyses the conditions and
      processes behind the development and specific designs of such facilities. It
      first looks at the intertwinement, at the socio-structural level, of different
      transborder developments in which the facilities' emergence is embedded. Second,
      it analyses the processes that accompany the emergence, development and
      organisation of these facilities at the local level. In this regard, it points
      out the central role of the facility operators as transnational actors who
      mediate between different frames of reference and groups of actors involved in
      these facilities. It concludes that the processes of mediation and intertwining
      are an important and distinctive feature of the emergence of these facilities,
      necessitated by the fact that, although the facilities are located in Thailand,
      their 'markets' are in the German-speaking countries of their target groups.

PMID- 29180943
TI  - Transnational grandparenting in the digital age: mediated co-presence and
      childcare in the case of Romanian migrants in Switzerland and Canada.
AB  - Taking transnational families of Romanian migrants in Canada and Switzerland as a
      case in point, this paper accounts for the emergence of new patterns of
      "grandparenting" and "doing family" practices in the digital age, based on ICTs
      mediated co-presence. It shows that migrants' parents are able to acquire
      manifold technological skills in order to cope with distance and separation and
      to improve the quality of their interaction and relationships with children and
      grandchildren living abroad. Ordinary co-presence routines within polymedia
      environments allow grandparents to take on their role as childcare providers
      across borders and develop new transnational lifestyles. Thus, despite
      contrasting feelings of well-being and distress that mediated co-presence
      generates, migrants' parents are able to place themselves as key actors within
      the transnational family in the digital society and invent new grandparenting
      practices.

PMID- 29180944
TI  - Presenteeism, stress resilience, and physical activity in older manual workers: a
      person-centred analysis.
AB  - This study used a person-centred approach to explore typologies of older manual
      workers based on presenteeism, stress resilience, and physical activity. Older
      manual workers (n = 217; 69.1% male; age range 50-77; M age = 57.11 years; SD =
      5.62) from a range of UK-based organisations, representing different manual job
      roles, took part in the study. A cross-sectional survey design was used. Based on
      the three input variables: presenteeism, stress resilience and physical activity,
      four distinct profiles were identified on using Latent Profile Analysis. One
      group ('High sport/exercise and well-functioning'; 5.50%) engaged in high levels
      of sport/exercise and exhibited low levels of stress resilience and all types of
      presenteeism. Another profile ('Physically burdened'; 9.70%) reported high levels
      of work and leisure-time physical activity, low stress resilience, as well as
      high levels of presenteeism due to physical and time demands. A 'Moderately
      active and functioning' group (46.50%) exhibited moderate levels on all
      variables. Finally, the fourth profile ('Moderately active with high
      presenteeism'; 38.20%) reported engaging in moderate levels of physical activity
      and had relatively high levels of stress resilience, yet also high levels of
      presenteeism. The profiles differed on work affect and health perceptions largely
      in the expected directions. There were no differences between the profiles in
      socio-demographics. These results highlight complex within-person interactions
      between presenteeism, stress resilience, and physical activity in older manual
      workers. The identification of profiles of older manual workers who are at risk
      of poor health and functioning may inform targeted interventions to help retain
      them in the workforce for longer.

PMID- 29180945
TI  - Career histories as determinants of gendered retirement timing in the Danish and
      Swedish pension systems.
AB  - After reforms in pension systems had taken place in most European countries
      within the last two decades, the concern was raised that women may be
      disadvantaged by these reforms. It is suggested that they are faced with a higher
      financial need to work longer. Retrospective data from SHARELIFE are used to run
      an event history analysis on the timing of the final employment exit, separately
      for gender, country and exit cohort. This study aims to disentangle the influence
      of gendered labour markets and pension regulations on retirement timing by
      investigating conditions in Denmark and Sweden. Some evidence was found that
      women compensate for lower labour market attachment due to long part-time periods
      by working longer, especially in younger cohorts. This seems to depend on the
      pension system. In countries with broad basic pensions, high replacement rates
      for low-income groups and fewer penalties for early retirement, the compensation
      is suggested to be less frequent. This study indicates the growing importance of
      the "compensation hypothesis" compared to the "status maintenance hypothesis" of
      previous careers in relation with retirement timing.

PMID- 29180946
TI  - Educational inequalities in late-life depression across Europe: results from the
      generations and gender survey.
AB  - This study explores country- and gender-stratified educational differences in
      depression among older adults from 10 European countries. We examine inequalities
      in both absolute (prevalence differences) and relative (odds ratios) terms and in
      bivariate and multivariate models. We use cross-sectional, nationally
      representative data from the generations and gender survey. The analysis
      comprises 27,331 Europeans aged 60-80. Depression is measured with a seven-item
      version of the Center for Epidemiologic Studies Depression scale. Findings show
      considerable between-country heterogeneity in late-life depression. An East-West
      gradient is evident, with rates of depression up to three times higher in Eastern
      European than in Scandinavian countries. Rates are about twice as high among
      women than men in all countries. Findings reveal marked absolute educational gaps
      in depression in all countries, yet the gaps are larger in weaker welfare states.
      This pattern is less pronounced for the relative inequalities, especially for
      women. Some countries observe similar relative inequalities but vastly different
      absolute inequalities. We argue that the absolute differences are more important
      for social policy development and evaluation. Educational gradients in depression
      are strongly mediated by individual-level health and financial variables.
      Socioeconomic variation in late-life depression is greater in countries with
      poorer economic development and welfare programs.

PMID- 29180948
TI  - Validity of the de Jong Gierveld Loneliness Scale in Spanish older population:
      competitive structural models and item response theory.
AB  - Loneliness is a subjective measure of one's state of mind and the negative
      feelings about one's level of social contact, which usually involves an unwanted
      discrepancy between existing and desired relationships. It is measured through
      self-reported questionnaires, among which a widely used one is the de Jong
      Gierveld Loneliness Scale (DJGLS). Although it has been previously tested and
      proven to be a reliable tool for measuring loneliness of Spanish older people,
      some relevant research questions remain unsolved. Therefore, this article aims to
      present a validity study of the Spanish version of the DJGLS for its use with
      older people, by establishing its factorial validity; studying the adequateness
      of a Rasch model underlying participants' responses; offering evidence of its
      reliability; and testing for convergent and discriminant validity. Data were
      obtained in a survey conducted with older adults attending Lifelong Learning
      programs in Valencia (Spain). The sample consisted of 335 people aged 55 years or
      older. Sociodemographic data were collected, and loneliness was measured with the
      DJGLS and the UCLA Loneliness Scale. Results have supported a unidimensional
      substantive structure, but with minor method effects associated with negatively
      worded items. In terms of multidimensional IRT analysis, the 2 Parameters
      Logistic Model fitted the data well and offered better information functions than
      the Rasch model. Reliability and criterion-related validity estimates were
      adequate.

PMID- 29180947
TI  - Prevalence and related factors of successful aging among Chinese rural elders
      living in nursing homes.
AB  - Few studies focus on the prevalence and related factors of successful aging (SA)
      among Chinese rural elders living in nursing homes. This study aims to make an
      operational definition of successful aging, estimate the prevalence of SA, and
      identify factors related to SA among Chinese rural elders living in nursing
      homes. Data for this cross-sectional study were collected by face-to-face
      interviews in five rural public nursing homes. A total of 205 elders aged 60
      years and above were asked to answer a series of questions. Descriptive analysis,
      independent sample t tests, chi2 tests, and multivariate logistic regression were
      used to show the prevalence and related factors of SA. The prevalence of SA in
      this population is 17.6% based on a multidimensional construct composed of: few
      chronic diseases, good cognitive and physical functioning, good mental health,
      and active social engagement. The logistic regression results indicate that
      successful agers are more likely to be younger, married, resilient, and better
      off economically, whereas gender, education, and social support are not related
      to SA independently. This model accounts for 45.8% of the variance in SA. These
      results suggest some tentative recommendations for elders, relevant decision
      makers or employees in nursing homes, and administrative bodies. More rigorous
      longitudinal design is necessary to investigate the causality of the related
      factors and SA.

PMID- 29180949
TI  - Electrically Oscillating Plasmonic Nanoparticles for Enhanced DNA Vaccination
      against Hepatitis C Virus.
AB  - The promise of DNA vaccines is far-reaching. However, the development of potent
      immunization methods remains a key challenge for its use in clinical
      applications. Here, an approach for in vivo DNA vaccination by electrically
      activated plasmonic Au nanoparticles is reported. The electrical excitation of
      plasmonic nanoparticles can drive vibrational and dipole-like oscillations that
      are able to disrupt nearby cell membranes. In combination with their intrinsic
      ability to focus and magnify the electric field on the surface of cells, Au
      nanoparticles allow enhanced cell poration and facilitate the uptake of DNA
      vaccine. Mice immunized with this approach showed up to 100-fold higher gene
      expression compared to control treatments (without nanoparticles) and exhibited
      significantly increased levels of both antibody and cellular immune responses
      against a model hepatitis C virus DNA vaccine. This approach can be tuned to
      establish controlled and targeted delivery of different types of therapeutic
      molecules into cells and live animals as well.

PMID- 29180950
TI  - Dissociable Electroencephalograph Correlates of Visual Awareness and Feature
      Based Attention.
AB  - Background: The relationship between awareness and attention is complex and
      controversial. A growing body of literature has shown that the neural bases of
      consciousness and endogenous attention (voluntary attention) are independent. The
      important role of exogenous attention (reflexive attention) on conscious
      experience has been noted in several studies. However, exogenous attention can
      also modulate subliminal processing, suggesting independence between the two
      processes. The question of whether visual awareness and exogenous attention rely
      on independent mechanisms under certain circumstances remains unanswered.
      Methods: In the current study, electroencephalograph recordings were conducted
      using 64 channels from 16 subjects while subjects attempted to detect faint speed
      changes of colored rotating dots. Awareness and attention were manipulated
      throughout trials in order to test whether exogenous attention and visual
      awareness rely on independent mechanisms. Results: Neural activity related to
      consciousness was recorded in the following cue-locked time-windows (event
      related potential, cluster- based permutation test): 0-50, 150-200, and 750-800
      ms. With a more liberal threshold, the inferior occipital lobe was found to be
      the source of awareness-related activity in the 0-50 ms range. In the later 150
      200 ms range, activity in the fusiform and post-central gyrus was related to
      awareness. Awareness-related activation in the later 750-800 ms range was more
      widely distributed. This awareness-related activation pattern was quite different
      from that of attention. Attention-related neural activity was emphasized in the
      750-800 ms time window and the main source of attention-related activity was
      localized to the right angular gyrus. These results suggest that exogenous
      attention and visual consciousness correspond to different and relatively
      independent neural mechanisms and are distinct processes under certain
      conditions.

PMID- 29180951
TI  - P2X2 Dominant Deafness Mutations Have No Negative Effect on Wild-Type Isoform:
      Implications for Functional Rescue and in Deafness Mechanism.
AB  - The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits.
      Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R
      can cause autosomal dominant nonsyndromic hearing loss. However, the underlying
      mechanism remains unclear. The fact that heterozygous mutations cause deafness
      suggests that the mutations may have dominant-negative effect (DNE) on wild-type
      (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study,
      the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated.
      We found that sole transfection of both V60L and G353R deafness mutants could
      efficiently target to the plasma membrane, like WT P2X2, but exhibit a
      significantly reduced response to ATP stimulation. Both mutants reduced the
      channel conductance, but G353R mutation also altered the voltage dependency. Co
      expression with WT P2X2 could restore the response to ATP. As the ratio of WT
      P2X2 vs. mutants increased, the response to ATP was also increased. Computer
      modeling confirmed that both V60L and G353R dominant-deafness mutant subunits do
      not have any negative effect on WT P2X2 subunit, when assembled as a
      heterotrimer. Improper docking or defective gating is the more likely mechanism
      for impaired channel function by these P2X2 deafness mutations. These results
      suggest that P2X2 dominant deafness mutations do not have negative effects on WT
      P2X2 isoforms, and that adding additional WT P2X2 could rescue the lost channel
      function caused by the deafness mutations. These P2X2 dominant deafness mutations
      may have negative-effects on other partners leading to hearing loss.

PMID- 29180952
TI  - Maintenance of Positional Identity of Neural Progenitors in the Embryonic and
      Postnatal Telencephalon.
AB  - Throughout embryonic development and into postnatal life, regionally distinct
      populations of neural progenitor cells (NPCs) collectively generate the many
      different types of neurons that underlie the complex structure and function of
      the adult mammalian brain. At very early stages of telencephalic development,
      NPCs become organized into regional domains that each produce different subsets
      of neurons. This positional identity of NPCs relates to the regional expression
      of specific, fate-determining homeodomain transcription factors. As development
      progresses, the brain undergoes vast changes in both size and shape, yet
      important aspects of NPC positional identity persist even into the postnatal
      brain. How can NPC positional identity, which is established so early in brain
      development, endure the many dynamic, large-scale and complex changes that occur
      over a relatively long period of time? In this Perspective article, we review
      data and concepts derived from studies in Drosophila regarding the function of
      homeobox (Hox) genes, Polycomb group (PcG) and trithorax group (trxG) chromatin
      regulators. We then discuss how this knowledge may contribute to our
      understanding of the maintenance of positional identity of NPCs in the mammalian
      telencephalon. Similar to the axial body plan of Drosophila larvae, there is a
      segmental nature to NPC positional identity, with loss of specific homeodomain
      transcription factors causing homeotic-like shifts in brain development. Finally,
      we speculate about the role of mammalian PcG and trxG factors in the long-term
      maintenance of NPC positional identity and certain neurodevelopmental disorders.

PMID- 29180953
TI  - Roles of Glial Cells in Sculpting Inhibitory Synapses and Neural Circuits.
AB  - Glial cells are essential for every aspect of normal neuronal development,
      synapse formation, and function in the central nervous system (CNS). Astrocytes
      secrete a variety of factors that regulate synaptic connectivity and circuit
      formation. Microglia also modulate synapse development through phagocytic
      activity. Most of the known actions of CNS glial cells are limited to roles at
      excitatory synapses. Nevertheless, studies have indicated that both astrocytes
      and microglia shape inhibitory synaptic connections through various mechanisms,
      including release of regulatory molecules, direct contact with synaptic
      terminals, and utilization of mediators in the extracellular matrix. This review
      summarizes recent investigations into the mechanisms underlying CNS glial cell
      mediated inhibitory synapse development.

PMID- 29180955
TI  - Dissociable Role of Corticotropin Releasing Hormone Receptor Subtype 1 on
      Dopaminergic and D1 Dopaminoceptive Neurons in Cocaine Seeking Behavior.
AB  - The ability of many drugs of abuse, including cocaine, to mediate reinforcement
      and drug-seeking behaviors is in part mediated by the corticotropin-releasing
      hormone (CRH) system, in which CRH exerts its effects partly via the CRH receptor
      subtype 1 (CRHR1) in extra-hypothalamic areas. In fact, CRHR1 expressed in
      regions of the mesolimbic dopamine (DA) system have been demonstrated to modify
      cocaine-induced DA release and alter cocaine-mediated behaviors. Here we examined
      the role of neuronal selectivity of CRHR1 within the mesolimbic system on cocaine
      induced behaviors. First we used a transgenic mouse line expressing GFP under the
      control of the Crhr1 promoter for double fluorescence immunohistochemistry to
      demonstrate the cellular location of CRHR1 in both dopaminergic and D1
      dopaminoceptive neurons. We then studied cocaine sensitization, self
      administration, and reinstatement in inducible CRHR1 knockouts using the
      CreERT2/loxP in either dopamine transporter (DAT)-containing neurons (DAT-Crhr1)
      or dopamine receptor 1 (D1)-containing neurons (D1-Crhr1). For sensitization
      testing, mice received five daily injections of cocaine (15 mg/kg IP). For self
      administration, mice received eight daily 2 h cocaine (0.5 mg/kg per infusion)
      self-administration sessions followed by extinction and reinstatement testing.
      There were no differences in the acute or sensitized locomotor response to
      cocaine in DAT-Crhr1 or D1-Crhr1 mice and their respective controls. Furthermore,
      both DAT-Crhr1 and D1-Crhr1 mice reliably self-administered cocaine at the level
      of controls. However, DAT-Crhr1 mice demonstrated a significant increase in cue
      induced reinstatement relative to controls, whereas D1-Crhr1 mice demonstrated a
      significant decrease in cue-induced reinstatement relative to controls. These
      data demonstrate the involvement of CRHR1 in cue-induced reinstatement following
      cocaine self-administration, and implicate a bi-directional role of CRHR1 for
      cocaine craving.

PMID- 29180954
TI  - Disrupted Co-activation of Interneurons and Hippocampal Network after Focal
      Kainate Lesion.
AB  - GABAergic interneurons are known to control activity balance in physiological
      conditions and to coordinate hippocampal networks during cognitive tasks. In
      temporal lobe epilepsy interneuron loss and consecutive network imbalance could
      favor pathological hypersynchronous epileptic discharges. We tested this
      hypothesis in mice by in vivo unilateral epileptogenic hippocampal kainate lesion
      followed by in vitro recording of extracellular potentials and patch-clamp from
      GFP-expressing interneurons in CA3, in an optimized recording chamber. Slices
      from lesioned mice displayed, in addition to control synchronous events, larger
      epileptiform discharges. Despite some ipsi/contralateral and layer variation,
      interneuron density tended to decrease, average soma size to increase. Their
      membrane resistance decreased, capacitance increased and contralateral
      interneuron required higher current intensity to fire action potentials.
      Examination of synchronous discharges of control and larger amplitudes, revealed
      that interneurons were biased to fire predominantly with the largest population
      discharges. Altogether, these observations suggest that the overall effect of
      reactive cell loss, hypertrophy and reduced contralateral excitability
      corresponds to interneuron activity tuning to fire with larger population
      discharges. Such cellular and network mechanisms may contribute to a runaway path
      toward epilepsy.

PMID- 29180956
TI  - Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain
      Structure and Substance Use.
AB  - During adolescence, problems reflecting cognitive, behavioral and affective
      dysregulation, such as inattention and emotional dyscontrol, have been observed
      to be associated with substance use disorder (SUD) risks and outcomes. Prior
      studies have typically been with small samples, and have typically not included
      comprehensive measurement of executive dysfunction domains. The relationships of
      executive dysfunction in daily life with performance based testing of cognitive
      skills and structural brain characteristics, thought to be the basis for
      executive functioning, have not been definitively determined. The aims of this
      study were to determine the relationships between executive dysfunction in daily
      life, measured by the Behavior Rating Inventory of Executive Function (BRIEF),
      cognitive skills and structural brain characteristics, and SUD risks, including a
      global SUD risk indicator, sleep quality, and risky alcohol and cannabis use. In
      addition to bivariate relationships, multivariate models were tested. The
      subjects (n = 817; ages 12 through 21) were participants in the National
      Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. The
      results indicated that executive dysfunction was significantly related to SUD
      risks, poor sleep quality, risky alcohol use and cannabis use, and was not
      significantly related to cognitive skills or structural brain characteristics. In
      multivariate models, the relationship between poor sleep quality and risky
      substance use was mediated by executive dysfunction. While these cross-sectional
      relationships need to be further examined in longitudinal analyses, the results
      suggest that poor sleep quality and executive dysfunction may be viable
      preventive intervention targets to reduce adolescent substance use.

PMID- 29180957
TI  - Age-Related Brain Activation Changes during Rule Repetition in Word-Matching.
AB  - Objective: The purpose of this study was to explore the age-related brain
      activation changes during a word-matching semantic-category-based task, which
      required either repeating or changing a semantic rule to be applied. In order to
      do so, a word-semantic rule-based task was adapted from the Wisconsin Sorting
      Card Test, involving the repeated feedback-driven selection of given pairs of
      words based on semantic category-based criteria. Method: Forty healthy adults (20
      younger and 20 older) performed a word-matching task while undergoing a fMRI scan
      in which they were required to pair a target word with another word from a group
      of three words. The required pairing is based on three word-pair semantic rules
      which correspond to different levels of semantic control demands: functional
      relatedness, moderately typical-relatedness (which were considered as low control
      demands), and atypical-relatedness (high control demands). The sorting period
      consisted of a continuous execution of the same sorting rule and an inferred
      trial-by-trial feedback was given. Results: Behavioral performance revealed
      increases in response times and decreases of correct responses according to the
      level of semantic control demands (functional vs. typical vs. atypical) for both
      age groups (younger and older) reflecting graded differences in the repetition of
      the application of a given semantic rule. Neuroimaging findings of significant
      brain activation showed two main results: (1) Greater task-related activation
      changes for the repetition of the application of atypical rules relative to
      typical and functional rules, and (2) Changes (older > younger) in the inferior
      prefrontal regions for functional rules and more extensive and bilateral
      activations for typical and atypical rules. Regarding the inter-semantic rules
      comparison, only task-related activation differences were observed for functional
      > typical (e.g., inferior parietal and temporal regions bilaterally) and atypical
      > typical (e.g., prefrontal, inferior parietal, posterior temporal, and
      subcortical regions). Conclusion: These results suggest that healthy cognitive
      aging relies on the adaptive changes of inferior prefrontal resources involved in
      the repetitive execution of semantic rules, thus reflecting graded differences in
      support of task demands.

PMID- 29180958
TI  - Changing Artificial Playback Speed and Real Movement Velocity Do Not
      Differentially Influence the Excitability of Primary Motor Cortex during
      Observation of a Repetitive Finger Movement.
AB  - Action observation studies have investigated whether changing the speed of the
      observed movement affects the action observation network. There are two types of
      speed-changing conditions; one involves "changes in actual movement velocity,"
      and the other is "manipulation of video speed." Previous studies have
      investigated the effects of these conditions separately, but to date, no study
      has directly investigated the differences between the effects of these
      conditions. In the "movement velocity condition," increased velocity is
      associated with increased muscle activity; however, this change of muscle
      activities is not shown in the "video speed condition." Therefore, a difference
      in the results obtained under these conditions could be considered to reflect a
      difference in muscle activity of actor in the video. The aim of the present study
      was to investigate the effects of different speed-changing conditions and
      spontaneous movement tempo (SMT) on the excitability of primary motor cortex (M1)
      during action observation, as assessed by motor-evoked potentials (MEPs)
      amplitudes induced by transcranial magnetic stimulation (TMS). A total of 29
      healthy subjects observed a video clip of a repetitive index or little finger
      abduction movement under seven different speed conditions. The video clip in the
      movement velocity condition showed repetitive finger abduction movements made in
      time with an auditory metronome, at frequencies of 0.5, 1, 2, and 3 Hz. In the
      video speed condition, playback of the 1-Hz movement velocity condition video
      clip was modified to show movement frequencies of 0.5, 2, or 3 Hz (Hz-Fake). TMS
      was applied at the time of maximal abduction and MEPs were recorded from two
      right-hand muscles. There were no differences in M1 excitability between the
      movement velocity and video speed conditions. Moreover, M1 excitability did not
      vary across the speed conditions for either presentation condition. Our findings
      suggest that changing playback speed and actual differences in movement velocity
      do not differentially influence M1 excitability during observation of a simple
      action task, such as repetitive finger movement, and that it is not affected by
      SMT. In simple and meaningless observational task, people might not be able to
      recognize the difference in muscle activity of actor in the video.

PMID- 29180960
TI  - Association of Cerebral Small Vessel Disease Burden and Health-Related Quality of
      Life after Acute Ischemic Stroke.
AB  - Objective: Cerebral small vessel disease (SVD) is associated with increased
      mortality, disability and cognitive decline, depression in stroke survivors. This
      study examined the association between SVD burden, defined by a combination of
      SVD markers, and health-related quality of life (HRQoL) in acute ischemic stroke.
      Methods: Patients admitted with acute ischemic stroke of any etiology were
      prospectively screened between January 2010 to December 2014 and enrolled in the
      study if they met study entry criteria. HRQoL was evaluated with the 12-item
      Stroke Specific Quality of Life (SSQoL) at 3 months after the onset of acute
      ischemic stroke. SVD was ascertained by the presence of any of the SVD markers
      including lacune, white matter hyperintensities (WMH), cerebral microbleeds (CMB)
      and enlarged perivascular spaces (EPVS) in the basal ganglia or their
      combinations on brain magnetic resonance imaging (MRI). The presence of each
      individual marker scored 1 point and was summed up to generate an ordinal "SVD
      score" (0-4) capturing total SVD burden. Linear regression was used to determine
      the associations between SVD burden and HRQoL. Results: Of the743 acute ischemic
      stroke patients that formed he study sample (mean age: 66.3 +/- 10.6 years; 41.7%
      women), 49.3%, 22.5%, 16.0%, 9.2% and 3.1% had SVD scores of 0, 1, 2, 3 and 4,
      respectively. After adjusting for demographic, clinical and imaging variables,
      the SVD score was independently associated with lower overall score of SSQoL (B =
      -1.39, SE = 0.56, p = 0.01), and its domains of mobility (B = -0.41, SE = 0.10, p
      < 0.001) and vision (B = -0.12, SE = 0.06, p = 0.03). Acute infract volume (B = 
      1.44, SE = 0.54, p = 0.01), functional independence (B = 5.69, SE = 0.34, p <
      0.001) and anxious (B = -1.13, SE = 0.23, p < 0.001) and depressive symptoms (B =
      -3.41, SE = 0.22, p < 0.001) were also the significant predictors of the overall
      score of SSQoL. Conclusion: The brain's SVD burden predicts lower HRQoL,
      predominantly in domains of mobility and vision at 3 months after acute ischemic
      stroke. The evaluation of SVD burden could facilitate developing individual
      treatment strategies.

PMID- 29180959
TI  - Family Income, Cumulative Risk Exposure, and White Matter Structure in Middle
      Childhood.
AB  - Family income is associated with gray matter morphometry in children, but little
      is known about the relationship between family income and white matter structure.
      In this paper, using Tract-Based Spatial Statistics, a whole brain, voxel-wise
      approach, we examined the relationship between family income (assessed by income
      to-needs ratio) and white matter organization in middle childhood (N = 27, M =
      8.66 years). Results from a non-parametric, voxel-wise, multiple regression
      (threshold-free cluster enhancement, p < 0.05 FWE corrected) indicated that lower
      family income was associated with lower white matter organization [assessed by
      fractional anisotropy (FA)] for several clusters in white matter tracts involved
      in cognitive and emotional functions including fronto-limbic circuitry (uncinate
      fasciculus and cingulum bundle), association fibers (inferior longitudinal
      fasciculus, superior longitudinal fasciculus), and corticospinal tracts. Further,
      we examined the possibility that cumulative risk (CR) exposure might function as
      one of the potential pathways by which family income influences neural outcomes.
      Using multiple regressions, we found lower FA in portions of these tracts,
      including those found in the left cingulum bundle and left superior longitudinal
      fasciculus, was significantly related to greater exposure to CR (beta = -0.47, p
      < 0.05 and beta = -0.45, p < 0.05).

PMID- 29180961
TI  - Ginsenoside-Rb1-Mediated Anti-angiogenesis via Regulating PEDF and miR-33a
      through the Activation of PPAR-gamma Pathway.
AB  - Angiogenesis is the formation of new blood vessels from the existing vasculature,
      which is involved in multiple biological processes, including atherosclerosis,
      ischemic heart disease, and cancer. Ginsenoside-Rb1 (Rb1), the most abundant
      ginsenoside isolated form Panax ginseng, has been identified as a promising anti
      angiogenic agent via the up-regulation of PEDF. However, the underlying molecular
      mechanisms still unknown. In the present study, human umbilical vein endothelial
      cells (HUVECs) were selected to perform in vitro assays. Rb1 (0-20 nM) treatment
      induced pigment epithelial-derived factor (PEDF) protein expression in
      concentration and time-dependent manners. Interestingly, it was also demonstrated
      that the exposure of Rb1 (10 nM) could increase PEDF protein expression without
      any alteration on mRNA level, suggesting the involvement of posttranscriptional
      regulation. Furthermore, bioinformatics predictions indicated the regulation of
      miR-33a on PEDF mRNA 3'-UTR, which was further confirmed by luciferase reporter
      gene assay and real-time PCR. Over-expression of pre-miR-33a was found to regress
      partly Rb1-mediated PEDF increment and anti-angiogenic effect in HUVECs.
      Additionally, Rb1-reduced miR-33a and increased PEDF expression was prevented by
      pre-incubation with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      antagonist (GW9662) or transfection with PPAR-gamma siRNA in HUVECs. Taken
      together, our findings demonstrated that Rb1 exerted anti-angiogenic effects
      through PPAR-gamma signaling pathway via modulating miR-33a and PEDF expressions.
      Thus, Rb1 may have the potential of being developed as an anti-angiogenic agent,
      however, further appropriate studies are warranted to evaluate the effect in
      vivo.

PMID- 29180962
TI  - Tetradecyl 2,3-Dihydroxybenzoate Improves the Symptoms of Diabetic Mice by
      Modulation of Insulin and Adiponectin Signaling Pathways.
AB  - Background: Tetradecyl 2,3-dihydroxybenzoate (ABG-001) derived from Chinese
      medicine, gentiana regescens Franch is a leading compound with NGF mimic effect,
      it can induce neurite outgrowth of PC12 cells via the IGF-1/PI3K/ERK signaling
      pathway. Thus, we inferred that this compound had anti-diabetic effect and used
      streptozocin (STZ)-induced diabetic mice to indicate it. Methods: ABG-001 was
      synthesized with 2,3-dihydroxybenzoic acid and tetradecyl alcohol under certain
      reaction conditions. STZ-induced diabetic mice were used to investigate anti
      diabetic effect. Oral glucose tolerance test, insulin tolerance test, RT-PCR,
      Western blot, ELISA assays and histological section were performed to do the
      analysis of action mechanism. Results: ABG-001 showed anti-diabetic effect in STZ
      induced diabetic mice. In diabetic mice, the anti-diabetic effect of ABG-001 at a
      dose of 20 mg/kg was equal with metformin at a dose of 140 mg/kg. Moreover,
      glucose tolerance and insulin sensitivity were significantly improved on diabetic
      mice. The plasma insulin, adiponectin and leptin were notably increased, whereas
      glucagon remarkably decreased. The gene expressions of adiponectin and leptin in
      adipose tissue, glucose transporter 4 and adiponectin receptor 1 in liver and
      gastrocnemius, ADR2 in hypothalamus and pancreas were obviously increased.
      Conclusion: ABG-001 exerts antidiabetic effects via modulation of insulin and
      adiponectin signaling pathways. This new type of molecule could be a promising
      drug candidate for treatment of diabetes.

PMID- 29180964
TI  - Retraction: An Antifungal Mechanism of Protolichesterinic Acid from the Lichen
      Usnea albopunctata Lies in the Accumulation of Intracellular ROS and Mitochondria
      Mediated Cell Death Due to Apoptosis in Candida tropicalis.
AB  - [This retracts the article on p. 301 in vol. 8, PMID: 28611662.].

PMID- 29180963
TI  - Spinal Cord Molecular and Cellular Changes Induced by Adenoviral Vector- and Cell
      Mediated Triple Gene Therapy after Severe Contusion.
AB  - The gene therapy has been successful in treatment of spinal cord injury (SCI) in
      several animal models, although it still remains unavailable for clinical
      practice. Surprisingly, regardless the fact that multiple reports showed motor
      recovery with gene therapy, little is known about molecular and cellular changes
      in the post-traumatic spinal cord following viral vector- or cell-mediated gene
      therapy. In this study we evaluated the therapeutic efficacy and changes in
      spinal cord after treatment with the genes encoding vascular endothelial growth
      factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG),
      and neuronal cell adhesion molecule (NCAM) applied using both approaches.
      Therapeutic genes were used for viral vector- and cell-mediated gene therapy in
      two combinations: (1) VEGF+GDNF+NCAM and (2) VEGF+ANG+NCAM. For direct gene
      therapy adenoviral vectors based on serotype 5 (Ad5) were injected intrathecally
      and for cell-mediated gene delivery human umbilical cord blood mononuclear cells
      (UCB-MC) were simultaneously transduced with three Ad5 vectors and injected
      intrathecally 4 h after the SCI. The efficacy of both treatments was confirmed by
      improvement in behavioral (BBB) test. Molecular and cellular changes following
      post-traumatic recovery were evaluated with immunofluorescent staining using
      antibodies against the functional markers of motorneurons (Hsp27, synaptophysin,
      PSD95), astrocytes (GFAP, vimentin), oligodendrocytes (Olig2, NG2, Cx47) and
      microglial cells (Iba1). Our results suggest that both approaches with
      intrathecal delivery of therapeutic genes may support functional recovery of post
      traumatic spinal cord via lowering the stress (down regulation of Hsp25) and
      enhancing the synaptic plasticity (up regulation of PSD95 and synaptophysin),
      supporting oligodendrocyte proliferation (up regulation of NG2) and myelination
      (up regulation of Olig2 and Cx47), modulating astrogliosis by reducing number of
      astrocytes (down regulation of GFAP and vimetin) and microglial cells (down
      regulation of Iba1).

PMID- 29180965
TI  - Oxidative Stress and Antioxidant System in Periodontitis.
AB  - Periodontitis is a common inflammatory disease, which is initiated by bacterial
      infection and subsequently progressed by aberrant host response. It can result in
      the destruction of teeth supporting tissues and have an influence on systemic
      health. When periodontitis occurs, reactive oxygen species, which are
      overproduced mostly by hyperactive neutrophils, could not be balanced by
      antioxidant defense system and cause tissues damage. This is characterized by
      increased metabolites of lipid peroxidation, DNA damage and protein damage. Local
      and systemic activities of antioxidants can also be influenced by periodontitis.
      Total antioxidant capacity, total oxidant status and oxidative stress index have
      been used to evaluate the oxidative stress associated with periodontitis. Studies
      have confirmed that inflammatory response in periodontitis is associated with an
      increased local and systemic oxidative stress and compromised antioxidant
      capacity. Our review focuses on increased oxidative stress in periodontal
      disease, specifically, on the relationship between the local and systemic
      biomarkers of oxidative stress and periodontitis and their association with the
      pathogenesis of periodontitis. Also, the relationship between periodontitis and
      systemic inflammation, and the effects of periodontal therapy on oxidative stress
      parameters will be discussed.

PMID- 29180966
TI  - Parathyroid Hormone-Related Protein Promotes Rat Stem Leydig Cell
      Differentiation.
AB  - The regulatory factors for stem Leydig cell development are largely unknown.
      Herein, we reported that parathyroid hormone-related protein (PTHrP) may be a
      factor to regulate this process. The effects of PTHrP on rat stem Leydig cell
      proliferation and differentiation were investigated using a stem Leydig cell
      culture system and an ethane dimethane sulfonate (EDS)-treated in vivo Leydig
      cell regeneration model. PTHrP (1,000 pg/ml) significantly increased medium
      testosterone level and up-regulated STAR, CYP17A1, and 17beta-HSD3 expressions.
      Co-treatment with PKA inhibitor H-89 or PKC inhibitor U73122 reversed PTHrP
      mediated increase of testosterone production in vitro. Intratesticular injection
      of PTHrP (100 ng/testis) into the Leydig cell-depleted testis from post-EDS day 7
      to 21 significantly increased serum testosterone level, up-regulated LHCGR,
      SCARB1, CYP11A1, 11beta-HSD1, and CYP17A1 expressions. It also enlarged Leydig
      cell size without affecting PCNA-labeled Leydig cell number. This indicates that
      PTHrP promotes stem Leydig cell differentiation. PTHrP in vivo increased CREB and
      p-CREB levels, suggesting that PTHrP acts via a PKA-CREB signaling pathway. In
      conclusion, PTHrP stimulates stem Leydig cell differentiation without affecting
      its proliferation, showing its novel action and mechanism on rat stem Leydig cell
      development.

PMID- 29180967
TI  - Efficacy and Tolerability of Different Interventions in Children and Adolescents
      with Attention Deficit Hyperactivity Disorder.
AB  - Background: Our study is an analysis of multiple publications involving assessing
      the comparable efficacy and tolerability of six interventions, which are
      lisdexamfetamine dimesylate (LDX), atomoxetine (ATX), methylphenidate (MPH),
      clonidine hydrochloride (CLON), guanfacine extended release (GXR), and bupropion,
      for young patients (6-18 years old) suffering from attention deficit
      hyperactivity disorder (ADHD). Methods: A conventional meta-analysis (MA) was
      performed to give direct comparisons and a network meta-analysis (NMA) was used
      to show the combination of direct and indirect evidence. Ranking preference for
      all the interventions under a certain outcome was given by the surface of
      cumulative ranking curve area (SUCRA). Results: Overall, 15,025 participants from
      73 studies were involved in our analysis. In the pairwise MA, LDX was associated
      with less withdrawal than ATX for lack of efficacy. MPH showed less effectiveness
      than LDX according to ADHD Rating Scale score. Based on the analysis of our NMA,
      significant results of efficacy that LDX is a competitive drug were observed when
      evaluating LDX in comparison with other drugs except for CLON. ATX and GXR
      presented higher rates of abdominal pain morbidity versus inactive treatment.
      Conclusion: The stimulants LDX and MPH are still highly recommended because they
      are highly effective and are tolerated well by patients. Among the non
      stimulants, CLON can be taken into consideration for its appreciable
      effectiveness and tolerability. ATX and GXR can be seen as moderate choices.

PMID- 29180969
TI  - Effect of Transcranial Direct Current Stimulation on Functional Capacity in
      Schizophrenia: A Study Protocol for a Randomized Controlled Trial.
AB  - : Schizophrenia patients elicit a wide range of psychopathology, including
      psychotic symptoms, mood symptoms, and cognitive impairment. Functional capacity
      is defined as the ability to perform everyday living skills, which is linked to
      cognition and real-world functional outcome. In a previous open trial, we
      demonstrated that transcranial direct current stimulation (tDCS), one of the
      neuromodulation methods, improved cognition and functional capacity in 28
      patients with schizophrenia. However, since it was a pilot study, a controlled
      trial is needed. Therefore, we present a study protocol for a randomized
      controlled trial designed to evaluate the effect of tDCS on functional capacity
      in patients with schizophrenia. This is a two-arm, parallel-design, randomized
      controlled trial, in which patients and assessors will be blinded. Patients
      meeting DSM-5 criteria for schizophrenia will be enrolled and randomized to
      receive either active or sham stimulation (with 10 sessions in five consecutive
      days). Functional capacity will be evaluated by the UCSD Performance-based Skills
      Assessment-Brief as primary outcome. Cognition, as measured by the Brief
      Assessment of Cognition in Schizophrenia, and psychotic symptoms, as measured by
      the Positive and Negative Syndrome Scale, will also be evaluated. Data will be
      collected at baseline, immediately after the last stimulation, and 1 and 2 months
      thereafter. If active stimulation elicits greater effects compared with those of
      sham stimulation, it may add to the efforts to improve functional outcomes by
      neuromodulation in patients with schizophrenia. Trial registration:
      UMIN000028224; https://upload.umin.ac.jp/cgi-open
      bin/ctr/ctr_view.cgi?recptno=R000032305.

PMID- 29180968
TI  - Food-Predicting Stimuli Differentially Influence Eye Movements and Goal-Directed
      Behavior in Normal-Weight, Overweight, and Obese Individuals.
AB  - Obese individuals have been shown to exhibit abnormal sensitivity to rewards and
      reward-predicting cues as for example food-associated cues frequently used in
      advertisements. It has also been shown that food-associated cues can increase
      goal-directed behavior but it is currently unknown, whether this effect differs
      between normal-weight, overweight, and obese individuals. Here, we investigate
      this question by using a Pavlovian-to-instrumental transfer (PIT) task in normal
      weight (N = 20), overweight (N = 17), and obese (N = 17) individuals.
      Furthermore, we applied eye tracking during Pavlovian conditioning to measure the
      participants' conditioned response as a proxy of the incentive salience of the
      predicted reward. Our results show that the goal-directed behavior of overweight
      individuals was more strongly influenced by food-predicting cues (i.e., stronger
      PIT effect) than that of normal-weight and obese individuals (p < 0.001). The
      weight groups were matched for age, gender, education, and parental education.
      Eye movements during Pavlovian conditioning also differed between weight
      categories (p < 0.05) and were used to categorize individuals based on their
      fixation style into "high eye index" versus "low eye index" as well. Our main
      finding was that the fixation style exhibited a complex interaction with the
      weight category. Furthermore, we found that normal-weight individuals of the
      group "high eye index" had higher body mass index within the healthy range than
      individuals of the group "low eye index" (p < 0.001), but this relationship was
      not found within in the overweight or obese groups (p > 0.646). Our findings are
      largely consistent with the incentive sensitization theory predicting that
      overweight individuals are more susceptible to food-related cues than normal
      weight controls. However, this hypersensitivity might be reduced in obese
      individuals, possibly due to habitual/compulsive overeating or differences in
      reward valuation.

PMID- 29180970
TI  - Cebranopadol, a Mixed Opioid Agonist, Reduces Cocaine Self-administration through
      Nociceptin Opioid and Mu Opioid Receptors.
AB  - Cocaine addiction is a widespread psychiatric condition still waiting for
      approved efficacious medications. Previous studies suggested that simultaneous
      activation of nociceptin opioid (NOP) and mu opioid (MOP) receptors could be a
      successful strategy to treat cocaine addiction, but the paucity of molecules co
      activating both receptors with comparable potency has hampered this line of
      research. Cebranopadol is a non-selective opioid agonist that at nanomolar
      concentration activates both NOP and MOP receptors and that recently reached
      phase-III clinical trials for cancer pain treatment. Here, we tested the effect
      of cebranopadol on cocaine self-administration (SA) in the rat. We found that
      under a fixed-ratio-5 schedule of reinforcement, cebranopadol (25 and 50 ug/kg)
      decreased cocaine but not saccharin SA, indicating a specific inhibition of
      psychostimulant consumption. In addition, cebranopadol (50 ug/kg) decreased the
      motivation for cocaine as detected by reduction of the break point measured in a
      progressive-ratio paradigm. Next, we found that cebranopadol retains its effect
      on cocaine consumption throughout a 7-day chronic treatment, suggesting a lack of
      tolerance development toward its effect. Finally, we found that only simultaneous
      blockade of NOP and MOP receptors by concomitant administration of the NOP
      antagonist SB-612111 (30 mg/kg) and naltrexone (2.5 mg/kg) reversed cebranopadol
      induced decrease of cocaine SA, demonstrating that cebranopadol activates both
      NOP and classical opioid receptors to exert its effect. Our data, together with
      the fairly advanced clinical development of cebranopadol and its good
      tolerability profile in humans, indicate that cebranopadol is an appealing
      candidate for cocaine addiction treatment.

PMID- 29180972
TI  - Why Women Wear High Heels: Evolution, Lumbar Curvature, and Attractiveness.
AB  - Despite the widespread use of high-heeled footwear in both developing and
      modernized societies, we lack an understanding of this behavioral phenomenon at
      both proximate and distal levels of explanation. The current manuscript advances
      and tests a novel, evolutionarily anchored hypothesis for why women wear high
      heels, and provides convergent support for this hypothesis across multiple
      methods. Using a recently discovered evolved mate preference, we hypothesized
      that high heels influence women's attractiveness via effects on their lumbar
      curvature. Independent studies that employed distinct methods, eliminated
      multiple confounds, and ruled out alternative explanations showed that when women
      wear high heels, their lumbar curvature increased and they were perceived as more
      attractive. Closer analysis revealed an even more precise pattern aligning with
      human evolved psychology: high-heeled footwear increased women's attractiveness
      only when wearing heels altered their lumbar curvature to be closer to an
      evolutionarily optimal angle. These findings illustrate how human evolved
      psychology can contribute to and intersect with aspects of cultural evolution,
      highlighting that the two are not independent or autonomous processes but rather
      are deeply intertwined.

PMID- 29180971
TI  - Increased Risk of Pulmonary Tuberculosis in Patients with Depression: A Cohort
      Study in Taiwan.
AB  - Background/objective: Tuberculosis (TB) and depression were major public health
      issues worldwide and the mutual causative relationships between them were not
      exhaustive. This study was performed to explore the association between
      depression, comorbidities, and the risk of pulmonary TB in Taiwan. Methods: The
      cohort study used the database of the Taiwan National Health Insurance Program.
      The depression group included 34,765 subjects aged 20-84 years with newly
      diagnosed depression from 2000 to 2012, and the non-depression group included
      138,187 randomly selected subjects without depression. Both depression and non
      depression groups were matched with respect to sex, age, and comorbidities. We
      explored the incidence of pulmonary TB at the end of 2013 in both the groups and
      used multivariable Cox proportional hazards regression model to explore the
      hazard ratio (HR) and 95% confidence interval (CI) for the risk of pulmonary TB
      associated with depression. Results: The overall incidence of pulmonary TB was
      1.16-fold greater in the depression group than that in the non-depression group
      (1.52 vs. 1.31 per 1,000 person-years, 95% CI 1.12, 1.21). The multivariable Cox
      proportional hazards regression analysis revealed that the adjusted HR of
      pulmonary TB was 1.15 for the depression group (95% CI 1.03, 1.28), compared with
      the non-depression group. Conclusion: Depression is associated with 1.15-fold
      increased hazard of pulmonary TB in Taiwan.

PMID- 29180973
TI  - Mothers, Intrinsic Math Motivation, Arithmetic Skills, and Math Anxiety in
      Elementary School.
AB  - Math anxiety is influenced by environmental, cognitive, and personal factors.
      Yet, the concurrent relationships between these factors have not been examined.
      To this end, the current study investigated how the math anxiety of 30 sixth
      graders is affected by: (a) mother's math anxiety and maternal behaviors
      (environmental factors); (b) children's arithmetic skills (cognitive factors);
      and (c) intrinsic math motivation (personal factor). A rigorous assessment of
      children's math anxiety was made by using both explicit and implicit measures.
      The results indicated that accessible self-representations of math anxiety, as
      reflected by the explicit self-report questionnaire, were strongly affected by
      arithmetic skills. However, unconscious cognitive constructs of math anxiety, as
      reflected by the numerical dot-probe task, were strongly affected by
      environmental factors, such as maternal behaviors and mothers' attitudes toward
      math. Furthermore, the present study provided preliminary evidence of
      intergenerational transmission of math anxiety. The conclusions are that in order
      to better understand the etiology of math anxiety, multiple facets of parenting
      and children's skills should be taken into consideration. Implications for
      researchers, parents, and educators are discussed.

PMID- 29180974
TI  - Effects of Two Linguistically Proximal Varieties on the Spectral and
      Coarticulatory Properties of Fricatives: Evidence from Athenian Greek and Cypriot
      Greek.
AB  - Several studies have explored the acoustic structure of fricatives, yet there has
      been very little acoustic research on the effects of dialects on the production
      of fricatives. This article investigates the effects of two linguistically
      proximal Modern Greek dialects, Athenian Greek and Cypriot Greek on the temporal,
      spectral, and coarticulatory properties of fricatives and aims to determine the
      acoustic properties that convey information about these two dialects. Productions
      of voiced and voiceless labiodental, dental, alveolar, palatal, and velar
      fricatives were extracted from a speaking task from typically speaking female
      adult speakers (25 Cypriot Greek and 20 Athenian Greek speakers). Measures were
      made of spectral properties, using a spectral moments analysis. The formants of
      the following vowel were measured and second degree polynomials of the formant
      contours were calculated. The findings showed that Athenian Greek and Cypriot
      Greek fricatives differ in all spectral properties across all places of
      articulation. Also, the co-articulatory effects of fricatives on following vowel
      were different depending on the dialect. Duration, spectral moments, and the
      starting frequencies of F1, F2, F3, and F4 contributed the most to the
      classification of dialect. These findings provide a solid evidence base for the
      manifestation of dialectal information in the acoustic structure of fricatives.

PMID- 29180975
TI  - Experience-Induced Change of Alcohol-Related Risk Perception in Patients with
      Alcohol Use Disorders.
AB  - The role of alcohol-related risk perception for effective treatment of alcohol
      use disorders (AUD) is still unclear. The present study on 101 alcohol-dependent
      patients undergoing a 10-week AUD treatment protocol investigated the
      relationship between alcohol-related risk perception and alcohol use with the
      hypotheses that (1) risk perception changes across treatment, (2) changes vary
      with treatment-related experiences of abstinence/relapse indicating 'risk
      reappraisal,' and (3) adjustment of perceived own vulnerability according to
      'risk reappraisal hypothesis' predicts abstinence during follow-up. Abstinence
      during treatment was related to a decrease, and relapse during treatment to a
      slight increase in perceived own risks. Abstinence during the 3-month follow-up
      varied with experience-induced risk reappraisal. The results show an impact of
      risk reappraisal on alcohol use and hence advocate a focus on risk reappraisal in
      AUD treatment.

PMID- 29180976
TI  - Are Clowns Good for Everyone? The Influence of Trait Cheerfulness on Emotional
      Reactions to a Hospital Clown Intervention.
AB  - Trait cheerfulness predicts individual differences in experiences and behavioral
      responses in various humor experiments and settings. The present study is the
      first to investigate whether trait cheerfulness also influences the impact of a
      hospital clown intervention on the emotional state of patients. Forty-two adults
      received a clown visit in a rehabilitation center and rated their emotional state
      and trait cheerfulness afterward. Facial expressions of patients during the clown
      visit were coded with the Facial Action Coding System. Looking at the total
      sample, the hospital clown intervention elicited more frequent facial expressions
      of genuine enjoyment (Duchenne smiles) than other smiles (Non-Duchenne smiles),
      and more Duchenne smiles went along with more perceived funniness, a higher level
      of global positive feelings and transcendence. This supports the notion that
      overall, hospital clown interventions are beneficial for patients. However, when
      considering individual differences in the receptiveness to humor, results
      confirmed that high trait cheerful patients showed more Duchenne smiles than low
      trait cheerful patients (with no difference in Non-Duchenne smiles), and reported
      a higher level of positive emotions than low trait cheerful individuals. In
      summary, although hospital clown interventions on average successfully raise the
      patients' level of positive emotions, not all patients in hospitals are equally
      susceptible to respond to humor with amusement, and thus do not equally benefit
      from a hospital clown intervention. Implications for research and practitioners
      are discussed.

PMID- 29180977
TI  - Adopting Basic Principles of the United Nations Academic Impact Initiative
      (UNAI): Can Cultural Differences Be Predicted from Value Orientations and
      Globalization?
AB  - The United Nations Academic Impact (UNAI) Initiative has set forth 10 Basic
      Principles for higher education. In the present study, a 10 item self-report
      questionnaire measuring personal endorsement of these principles has been tested
      by self-report questionnaires with university and post-graduate students from
      Austria, China, Cyprus, India, Nigeria, and Slovakia (total N = 976, N = 627
      female, mean age 24.7 years, s = 5.7). Starting from the assumptions of Moral
      Foundations Theory (MFT), we expected that personal attitudes toward the UNAI
      Basic Principles would be predicted by endorsement of various moral foundations
      as suggested by MFT and by the individual's degree of globalization. Whereas for
      the Austrian, Cypriot, and Nigerian sub- samples this assumption was largely
      confirmed, for the Chinese, Indian, and Slovak sub- samples only small amounts of
      the variance could be explained by regression models. All six sub-samples
      differed substantially with regard to their overall questionnaire responses: by
      five discriminant functions 83.6% of participants were classified correctly. We
      conclude that implementation of UNAI principles should adhere closely to the
      cultural requirements of the respective society and, where necessary should be
      accompanied by thorough informational campaigns about UN educational goals.

PMID- 29180978
TI  - Emotion Regulation Ability and Resilience in a Sample of Adolescents from a
      Suburban Area.
AB  - Earlier research has identified a remarkable number of related factors to
      resilience during adolescence. Historically, theoretical treatments of resilience
      have been focused almost exclusively on psychosocial levels of analysis to derive
      explanatory models. However, there is insufficient understanding of the role of
      emotion regulation explaining competent functioning despite the experience of
      adversity (resilience), especially during adolescence. This study explores the
      relationship between both, emotional regulation abilities and strategies, and
      resilience in a sample of adolescents from suburbs high-schools (Jerez de la
      Frontera, Spain). The study also examines how using different emotional
      regulation strategies may help the development of resilience levels at this
      stage. Participants of the study were 164 adolescents ranging from 13 to 16 years
      old (M = 13.98; SD = 0.66). Emotion regulation was measured using the Cognitive
      Emotional Regulation Questionnaire (CERQ, Garnefski et al., 2001), and sections D
      and H of Mayer-Salovey-Caruso Emotional Intelligence Test, a performance test
      (Emotion Regulation Ability sections, MSCEIT, Spanish version, Mayer et al.,
      2003). Resilience was evaluated with ERE (Educative Resilience Scale for children
      and adolescents, Saavedra and Castro, 2009). Verbal Intelligence (Yuste, 1997)
      and personality traits (Cattell and Cattell, 1986) were assessed as two
      independent variables. Results supported the idea that emotion regulation ability
      (MSCEIT, D and H sections, Extremera et al., 2006) is a significant predictor of
      adolescents' resilience. Moreover, cognitive regulation strategies, such as
      positive reappraisal, predicted perceived resilience among students. Sociability
      (A factor of HSPQ, sociability) also correlated with resilience levels. Hence,
      these results are promising, implying that emotion regulation ability may act as
      a helpful tool preventing adolescents from irrational risky behaviors, commonly
      assumed at this developmental stage.

PMID- 29180979
TI  - Clinical Characteristics and Predictors of Outcome for Onconeural Antibody
      Associated Disorders: A Retrospective Analysis.
AB  - Objective: To describe and analyze the clinical characteristics, laboratory data,
      management, and outcome of patients with onconeural antibody-associated disorders
      (OAAD) and identify predictors for poor outcome. Methods: This was a
      retrospective review of all patients with potential OAAD, who were hospitalized
      in Jinan General Hospital between September 2009 and July 2017. We clarified the
      diagnosis, collected comprehensive information and categorized patients into
      three groups: paraneoplastic neurological disorders (PNDs), autoimmune
      encephalitis (AE), and possible OAAD. Within the three groups, we analyzed a
      range of clinical and laboratory parameters and used univariate and multivariate
      regression analysis to identify predictors for poor outcome [modified Rankin
      Scale (mRS) = 3-6]. Results: From 158 patients, we identified 70 who fulfilled
      the criteria for OAAD, including 44 men (62.9%) and 26 women (37.1%). There were
      38 patients (54.3%) in the PNDs group, 14 patients (20%) in the AE group, and 18
      patients (25.7%) in the possible OAAD group. After the last follow-up, 14
      (36.8%), 9 (64.2%), and 12 (66.7%) had a good outcome (mRS = 0-2). However, 6
      (15.8%), 2 (14.3%), and 3 (16.7%) died, respectively. Univariate analysis showed
      that duration prior to the hospital (p = 0.0224) and urinary
      incontinence/retention (p = 0.0043) were associated with poor outcome (mRS = 3
      6). After multivariate regression analysis, urinary incontinence/retention (p =
      0.0388) and an immunocompromised state (p = 0.0247) remained as significant
      factors for poor outcome. Conclusion: Urinary incontinence/retention and an
      immunocompromised state represent significant predictors of a worse prognosis for
      patients with OAAD. By contrast, cerebrospinal fluid analysis showed that serum
      autoantibodies and tumor markers, the function of crucial organs,
      electrophysiology, and radiological findings were not associated with a poor
      outcome.

PMID- 29180980
TI  - Commentary: Parent-Reported Behavioral and Psychiatric Problems Mediate the
      Relationship between Sleep-Disordered Breathing and Cognitive Deficits in School
      Aged Children.

PMID- 29180981
TI  - Cerebral Microdialysis Monitoring to Improve Individualized Neurointensive Care
      Therapy: An Update of Recent Clinical Data.
AB  - Cerebral microdialysis (CMD) allows bedside semicontinuous monitoring of patient
      brain extracellular fluid. Clinical indications of CMD monitoring are focused on
      the management of secondary cerebral and systemic insults in acute brain injury
      (ABI) patients [mainly, traumatic brain injury (TBI), subarachnoid hemorrhage,
      and intracerebral hemorrhage (ICH)], specifically to tailor several routine
      interventions-such as optimization of cerebral perfusion pressure, blood
      transfusion, glycemic control and oxygen therapy-in the individual patient. Using
      CMD as clinical research tool has greatly contributed to identify and better
      understand important post-injury mechanisms-such as energy dysfunction,
      posttraumatic glycolysis, post-aneurysmal early brain injury, cortical spreading
      depressions, and subclinical seizures. Main CMD metabolites (namely,
      lactate/pyruvate ratio, and glucose) can be used to monitor the brain response to
      specific interventions, to assess the extent of injury, and to inform about
      prognosis. Recent consensus statements have provided guidelines and
      recommendations for CMD monitoring in neurocritical care. Here, we summarize
      recent clinical investigation conducted in ABI patients, specifically focusing on
      the role of CMD to guide individualized intensive care therapy and to improve our
      understanding of the complex disease mechanisms occurring in the immediate phase
      following ABI. Promising brain biomarkers will also be described.

PMID- 29180983
TI  - Therapy-Induced Growth and Sexual Maturation in a Developmentally Infantile Adult
      Patient with a PROP1 Mutation.
AB  - Background: Hypopituitarism as a result of PROP1 (prophet of PIT1) mutation
      represents the most common genetic cause of combined deficiency of pituitary
      hormones and due to growth retardation it is typically diagnosed in childhood.
      Case description: We present a unique case report of a prepubertal woman with
      growth retardation in whom combined pituitary hormone deficiency [central
      hypopituitarism, hypogonadism, and growth hormone (GH) deficiency] caused by
      homozygous mutation c.150delA in the PROP1 gene was diagnosed late in young
      adulthood due to unfavorable life circumstances. Through cautiously combined GH
      therapy and sex hormone therapy, she has achieved better than expected height
      (exceeding predictions based on family height) and sexual maturation, including
      regular menstrual cycles. Conclusion: Early diagnosis of panhypopituitarism due
      to PROP1 mutation is essential for successful treatment; however, our case report
      shows that carefully titrated GH treatment and sex hormone substitution, although
      initiated in adulthood, enable restoration of physiological growth and sexual
      development in a hormonally infantile adult woman with a PROP1 mutation.

PMID- 29180982
TI  - Resveratrol for Easing Status Epilepticus Induced Brain Injury, Inflammation,
      Epileptogenesis, and Cognitive and Memory Dysfunction-Are We There Yet?
AB  - Status epilepticus (SE) is a medical emergency exemplified by self-sustaining,
      unceasing seizures or swiftly recurring seizure events with no recovery between
      seizures. The early phase after SE event is associated with neurodegeneration,
      neuroinflammation, and abnormal neurogenesis in the hippocampus though the extent
      of these changes depends on the severity and duration of seizures. In many
      instances, over a period, the initial precipitating injury caused by SE leads to
      temporal lobe epilepsy (TLE), typified by spontaneous recurrent seizures,
      cognitive, memory and mood impairments associated with chronic inflammation,
      reduced neurogenesis, abnormal synaptic reorganization, and multiple molecular
      changes in the hippocampus. While antiepileptic drugs are efficacious for
      terminating or greatly reducing seizures in most cases of SE, they have proved
      ineffective for easing SE-induced epileptogenesis and TLE. Despite considerable
      advances in elucidating SE-induced multiple cellular, electrophysiological, and
      molecular changes in the brain, efficient strategies that prevent SE-induced TLE
      development are yet to be discovered. This review critically confers the efficacy
      and promise of resveratrol, a phytoalexin found in the skin of red grapes, for
      easing SE-induced neurodegeneration, neuroinflammation, aberrant neurogenesis,
      and for restraining the evolution of SE-induced brain injury into a chronic
      epileptic state typified by spontaneous recurrent seizures, and learning, memory,
      and mood impairments.

PMID- 29180984
TI  - Risk of Transmission of Antimicrobial Resistant Escherichia coli from Commercial
      Broiler and Free-Range Retail Chicken in India.
AB  - Multidrug-resistant Escherichia coli infections are a growing public health
      concern. This study analyzed the possibility of contamination of commercial
      poultry meat (broiler and free-range) with pathogenic and or multi-resistant E.
      coli in retail chain poultry meat markets in India. We analyzed 168 E. coli
      isolates from broiler and free-range retail poultry (meat/ceca) sampled over a
      wide geographical area, for their antimicrobial sensitivity, phylogenetic
      groupings, virulence determinants, extended-spectrum-beta-lactamase (ESBL)
      genotypes, fingerprinting by Enterobacterial Repetitive Intergenic Consensus
      (ERIC) PCR and genetic relatedness to human pathogenic E. coli using whole genome
      sequencing (WGS). The prevalence rates of ESBL producing E. coli among broiler
      chicken were: meat 46%; ceca 40%. Whereas, those for free range chicken were:
      meat 15%; ceca 30%. E. coli from broiler and free-range chicken exhibited varied
      prevalence rates for multi-drug resistance (meat 68%; ceca 64% and meat 8%; ceca
      26%, respectively) and extraintestinal pathogenic E. coli (ExPEC) contamination
      (5 and 0%, respectively). WGS analysis confirmed two globally emergent human
      pathogenic lineages of E. coli, namely the ST131 (H30-Rx subclone) and ST117
      among our poultry E. coli isolates. These results suggest that commercial poultry
      meat is not only an indirect public health risk by being a possible carrier of
      non-pathogenic multi-drug resistant (MDR)-E. coli, but could as well be the
      carrier of human E. coli pathotypes. Further, the free-range chicken appears to
      carry low risk of contamination with antimicrobial resistant and extraintestinal
      pathogenic E. coli (ExPEC). Overall, these observations reinforce the
      understanding that poultry meat in the retail chain could possibly be
      contaminated by MDR and/or pathogenic E. coli.

PMID- 29180985
TI  - Stratification of Diversity and Activity of Methanogenic and Methanotrophic
      Microorganisms in a Nitrogen-Fertilized Italian Paddy Soil.
AB  - Paddy fields are important ecosystems, as rice is the primary food source for
      about half of the world's population. Paddy fields are impacted by nitrogen
      fertilization and are a major anthropogenic source of methane. Microbial
      diversity and methane metabolism were investigated in the upper 60 cm of a paddy
      soil by qPCR, 16S rRNA gene amplicon sequencing and anoxic 13C-CH4 turnover with
      a suite of electron acceptors. The bacterial community consisted mainly of
      Acidobacteria, Chloroflexi, Proteobacteria, Planctomycetes, and Actinobacteria.
      Among archaea, Euryarchaeota and Bathyarchaeota dominated over Thaumarchaeota in
      the upper 30 cm of the soil. Bathyarchaeota constituted up to 45% of the total
      archaeal reads in the top 5 cm. In the methanogenic community, Methanosaeta were
      generally more abundant than the versatile Methanosarcina. The measured maximum
      methane production rate was 444 nmol gdwh-1, and the maximum rates of nitrate-,
      nitrite-, and iron-dependent anaerobic oxidation of methane (AOM) were 57 nmol,
      55 nmol, and 56 nmol gdwh-1, respectively, at different depths. qPCR revealed a
      higher abundance of 'Candidatus Methanoperedens nitroreducens' than
      methanotrophic NC10 phylum bacteria at all depths, except at 60 cm. These results
      demonstrate that there is substantial potential for AOM in fertilized paddy
      fields, with 'Candidatus Methanoperedens nitroreducens' archaea as a potential
      important contributor.

PMID- 29180986
TI  - Chlamydia trachomatis Strain Types Have Diversified Regionally and Globally with
      Evidence for Recombination across Geographic Divides.
AB  - Chlamydia trachomatis (Ct) is the leading cause of bacterial sexually transmitted
      diseases worldwide. The Ct Multi Locus Sequence Typing (MLST) scheme is effective
      in differentiating strain types (ST), deciphering transmission patterns and
      treatment failure, and identifying recombinant strains. Here, we analyzed 323
      reference and clinical samples, including 58 samples from Russia, an area that
      has not previously been represented in Ct typing schemes, to expand our knowledge
      of the global diversification of Ct STs. The 323 samples resolved into 84 unique
      STs, a 3.23 higher typing resolution compared to the gold standard single locus
      ompA genotyping. Our MLST scheme showed a high discriminatory index, D, of 0.98
      (95% CI 0.97-0.99) confirming the validity of this method for typing.
      Phylogenetic analyses revealed distinct branches for the phenotypic diseases of
      lymphogranuloma venereum, urethritis and cervicitis, and a sub-branch for ocular
      trachoma. Consistent with these findings, single nucleotide polymorphisms were
      identified that significantly correlated with each phenotype. While the overall
      number of unique STs per region was comparable across geographies, the number of
      STs was greater for Russia with a significantly higher ST/sample ratio of 0.45
      (95% CI: 0.35-0.53) compared to Europe or the Americas (p < 0.009), which may
      reflect a higher level of sexual mixing with the introduction of STs from other
      regions and/or reassortment of alleles. Four STs were found to be significantly
      associated with a particular geographic region. ST23 [p = 0.032 (95% CI: 1-23)],
      ST34 [p = 0.019 (95% CI: 1.1-25)]; and ST19 [p = 0.001 (95% CI: 1.7-34.7)] were
      significantly associated with Netherlands compared to Russia or the Americas,
      while ST 30 [p = 0.031 (95% CI: 1.1-17.8)] was significantly associated with the
      Americas. ST19 was significantly associated with Netherlands and Russia compared
      with the Americans [p = 0.001 (95% CI: 1.7-34.7) and p = 0.006 (95% CI: 1.5
      34.6), respectively]. Additionally, recombinant strains were ubiquitous in the
      data set [106 (32.8%)], although Europe had a significantly higher number than
      Russia or the Americas (p < 0.04), the majority of which were from Amsterdam [43
      (87.8%) of 49)]. The higher number of recombinants in Europe indicates selective
      pressure and/or adaptive diversification that will require additional studies to
      elucidate.

PMID- 29180987
TI  - Escherichia coli Fails to Efficiently Maintain the Activity of an Important
      Flavin Monooxygenase in Recombinant Overexpression.
AB  - This paper describes the measurement and analysis of in vivo activity and
      stability of cyclohexanone monooxygenase from Acinetobacter sp. NCIMB 9871
      (CHMO), a model Baeyer-Villiger monooxygenase, in the recombinant host
      Escherichia coli. This enzyme was often described as poorly stable in vitro, and
      has recently been found to deactivate rapidly in the absence of its essential
      cofactors and antioxidants. Its stability in vivo was scarcely studied, so far.
      Under conditions common for the overexpression of CHMO we investigated the
      ability of the host to support these properties using metabolomics. Our results
      showed that E. coli failed to provide the intracellular levels of cofactors
      required to functionally stabilize the enzyme, although the biocatalyst was
      produced in high concentration, and was invariably detected after protein
      synthesis had stopped. We thus infer that biotechnological applications of CHMO
      with this host relied on a residual activity of approximately 5-10%. Other
      microorganisms might offer a more efficient solution for recombinant production
      of CHMO and related enzymes.

PMID- 29180988
TI  - A Waking Review: Old and Novel Insights into the Spore Germination in
      Streptomyces.
AB  - The complex development undergone by Streptomyces encompasses transitions from
      vegetative mycelial forms to reproductive aerial hyphae that differentiate into
      chains of single-celled spores. Whereas their mycelial life - connected with
      spore formation and antibiotic production - is deeply investigated, spore
      germination as the counterpoint in their life cycle has received much less
      attention. Still, germination represents a system of transformation from
      metabolic zero point to a new living lap. There are several aspects of
      germination that may attract our attention: (1) Dormant spores are strikingly
      well-prepared for the future metabolic restart; they possess stable
      transcriptome, hydrolytic enzymes, chaperones, and other required macromolecules
      stabilized in a trehalose milieu; (2) Germination itself is a specific sequence
      of events leading to a complete morphological remodeling that include spore
      swelling, cell wall reconstruction, and eventually germ tube emergences; (3)
      Still not fully unveiled are the strategies that enable the process, including a
      single cell's signal transduction and gene expression control, as well as
      intercellular communication and the probability of germination across the whole
      population. This review summarizes our current knowledge about the germination
      process in Streptomyces, while focusing on the aforementioned points.

PMID- 29180990
TI  - The N-Terminus of Human Lactoferrin Displays Anti-biofilm Activity on Candida
      parapsilosis in Lumen Catheters.
AB  - Candida parapsilosis is a major cause of hospital-acquired infection, often
      related to parenteral nutrition administered via catheters and hand colonization
      of health care workers, and its peculiar biofilm formation ability on plastic
      surfaces. The mortality rate of 30% points to the pressing need for new
      antifungal drugs. The present study aimed at analyzing the inhibitory activity of
      the N-terminal lactoferrin-derived peptide, further referred to as hLF 1-11,
      against biofilms produced by clinical isolates of C. parapsilosis characterized
      for their biofilm forming ability and fluconazole susceptibility. hLF 1-11 anti
      biofilm activity was assessed in terms of reduction of biofilm biomass, metabolic
      activity, and observation of sessile cell morphology on polystyrene microtiter
      plates and using an in vitro model of catheter-associated C. parapsilosis biofilm
      production. Moreover, fluctuation in transcription levels of genes related to
      cell adhesion, hyphal development and extracellular matrix production upon
      peptide exposure were evaluated by quantitative real time RT-PCR. The results
      revealed that hLF 1-11 exhibits an inhibitory effect on biofilm formation by all
      the C. parapsilosis isolates tested, in a dose-dependent manner, regardless of
      their fluconazole susceptibility. In addition, hLF 1-11 induced a statistically
      significant dose-dependent reduction of preformed-biofilm cellular density and
      metabolic activity at high peptide concentrations only. Interestingly, when
      assessed in a catheter lumen, hLF 1-11 was able to induce a 2-log reduction of
      sessile cell viability at both the peptide concentrations used in RPMI diluted in
      NaPB. A more pronounced anti-biofilm effect was observed (3.5-log reduction) when
      a 10% glucose solution was used as experimental condition on both early and
      preformed C. parapsilosis biofilm. Quantitative real time RT-PCR experiments
      confirmed that hLF 1-11 down-regulates key biofilm related genes. The overall
      findings suggest hLF 1-11 as a promising candidate for the prevention of C.
      parapsilosis biofilm formation and to treatment of mature catheter-related C.
      parapsilosis biofilm formation.

PMID- 29180989
TI  - ANK1 and DnaK-TPR, Two Tetratricopeptide Repeat-Containing Proteins Primarily
      Expressed in Toxoplasma Bradyzoites, Do Not Contribute to Bradyzoite
      Differentiation.
AB  - Toxoplasma gondii is an important zoonotic pathogen infecting one third of the
      world population and numerous animals. A key factor to its wide distribution is
      the ability to interconvert between fast replicating tachyzoites and slowly
      growing bradyzoites, and to establish lifelong chronic infection in intermediate
      hosts. Although it is well accepted that stage conversion plays key roles in the
      pathogenesis and transmission of the parasite, little is known about the
      molecular mechanisms behind it. Using existing gene expression data from TOXODB
      and published work, we looked for proteins with novel functional domains and
      whose expression is up-regulated in the bradyzoite stage, hoping to find
      molecules that have critical roles in regulating stage conversion and bradyzoite
      formation. In this study we characterized two such proteins ANK1 and DnaK-TPR,
      both of which are primarily expressed in bradyzoites and contain novel motifs to
      mediate protein-protein interactions. Through CRISPR/CAS9 directed gene editing
      technology, both genes were individually knocked out in type 1 strain TgHB2 and
      type 2 strain ME49. Disruption of neither of these two genes affected the growth
      or replication of tachyzoites in vitro, consistent with their minimal expression
      at this stage. However, mutants lacking ANK1 or DnaK-TPR displayed modest
      virulence attenuation during mice infection. Surprisingly, inactivation of
      neither ANK1 nor DnaK-TPR seemed to have a significant impact on bradyzoite
      differentiation in vitro or cyst formation in vivo. These results suggest that
      ANK1 and DnaK-TPR probably do not directly contribute to bradyzoite
      differentiation, but likely affect other aspects of bradyzoite biology.

PMID- 29180991
TI  - Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum
      Metabolites in Chronic Hepatitis B Patients.
AB  - Chronic hepatitis B (CHB) is a global epidemic disease that results from
      hepatitis B virus (HBV) infection and may progress to severe liver failure,
      including liver fibrosis, cirrhosis and hepatocellular carcinoma. Previous
      evidence has indicated that the dysbiosis of gut microbiota occurs after liver
      virus infection and is associated with severe liver disease. The aim of this
      study is to elucidate the compositional and functional characteristics of the gut
      microbiota in early-stage CHB and to understand their influence on disease
      progression. We investigated the gut microbial composition of stool samples from
      85 CHB patients with low Child-Pugh scores and 22 healthy controls using the
      Illumina MiSeq sequencing platform. Furthermore, the serum metabolome of 40
      subjects was measured by gas chromatography mass spectrometry. Compared with the
      controls, significant alteration in the gut microbiota was observed in the CHB
      patients; 5 operational taxonomic units (OTUs) belonging to Actinomyces,
      Clostridium sensu stricto, unclassified Lachnospiraceae and Megamonas were
      increased, and 27 belonging to Alistipes, Asaccharobacter, Bacteroides,
      Butyricimonas, Clostridium IV, Escherichia/Shigella, Parabacteroides,
      Ruminococcus, unclassified Bacteria, unclassified Clostridiales, Unclassified
      Coriobacteriaceae, unclassified Enterobacteriaceae, unclassified Lachnospiraceae
      and unclassified Ruminococcaceae were decreased. The inferred metagenomic
      information of gut microbiota in CHB showed 21 enriched and 17 depleted KEGG
      level-2 pathways. Four OTUs, OTU38 (Streptococcus), OTU124 (Veillonella), OTU224
      (Streptococcus), and OTU55 (Haemophilus), had high correlations with hosts'
      hepatic function indices and 10 serum metabolites, including phenylalanine and
      tyrosine, which are aromatic amino acids that play pathogenic roles in liver
      disease. In particular, these 4 OTUs were significantly higher in patients with
      higher Child-Pugh scores, who also showed diminished phenylalanine and tryptophan
      metabolisms in the inferred gut metagenomic functions. These compositional and
      functional changes in the gut microbiota in early-stage CHB patients suggest the
      potential contributions of gut microbiota to the progression of CHB, and thus
      provide new insight into gut microbiota-targeted interventions to improve the
      prognosis of this disease.

PMID- 29180992
TI  - Phylogenetic Network Analysis Revealed the Occurrence of Horizontal Gene Transfer
      of 16S rRNA in the Genus Enterobacter.
AB  - Horizontal gene transfer (HGT) is a ubiquitous genetic event in bacterial
      evolution, but it seldom occurs for genes involved in highly complex
      supramolecules (or biosystems), which consist of many gene products. The ribosome
      is one such supramolecule, but several bacteria harbor dissimilar and/or chimeric
      16S rRNAs in their genomes, suggesting the occurrence of HGT of this gene.
      However, we know little about whether the genes actually experience HGT and, if
      so, the frequency of such a transfer. This is primarily because the methods
      currently employed for phylogenetic analysis (e.g., neighbor-joining, maximum
      likelihood, and maximum parsimony) of 16S rRNA genes assume point mutation-driven
      tree-shape evolution as an evolutionary model, which is intrinsically
      inappropriate to decipher the evolutionary history for genes driven by
      recombination. To address this issue, we applied a phylogenetic network analysis,
      which has been used previously for detection of genetic recombination in
      homologous alleles, to the 16S rRNA gene. We focused on the genus Enterobacter,
      whose phylogenetic relationships inferred by multi-locus sequence alignment
      analysis and 16S rRNA sequences are incompatible. All 10 complete genomic
      sequences were retrieved from the NCBI database, in which 71 16S rRNA genes were
      included. Neighbor-joining analysis demonstrated that the genes residing in the
      same genomes clustered, indicating the occurrence of intragenomic recombination.
      However, as suggested by the low bootstrap values, evolutionary relationships
      between the clusters were uncertain. We then applied phylogenetic network
      analysis to representative sequences from each cluster. We found three ancestral
      16S rRNA groups; the others were likely created through recursive recombination
      between the ancestors and chimeric descendants. Despite the large sequence
      changes caused by the recombination events, the RNA secondary structures were
      conserved. Successive intergenomic and intragenomic recombination thus shaped the
      evolution of 16S rRNA genes in the genus Enterobacter.

PMID- 29180993
TI  - Co-carcinogenesis: Human Papillomaviruses, Coal Tar Derivatives, and Squamous
      Cell Cervical Cancer.
AB  - Cervical cancer (CC) is the fourth most common cancers among women worldwide.
      Human papillomaviruses (HPVs) play a major role in the etiology of CC, with
      several lines of epidemiologic and experimental evidence supporting a role for
      non-viral (co-carcinogens) and host genetic factors in controlling the risk for
      progression to neoplasia among HPV-infected individuals. The role of co
      carcinogens in the development of CC is significant in the developing world where
      poor sanitation and other socio-economic conditions increase the infectious
      cancer burden. Here, we discuss how exposure to environmental factors such as
      coal tar derivatives from cigarette smoking, tar-based sanitary products, and
      inhaled smoke from biomass-burning stoves, could activate host pathways involved
      in development of HPV-associated squamous cell cancers in resource-limited
      settings. Understanding interactions between these pathways with certain
      oncogenic HPV genotypes may guide implementation of strategies for control and
      treatment of HPV-associated cancers that develop in populations at high risk of
      exposure to various co-carcinogens.

PMID- 29180994
TI  - Retraction: Molecular characterization of forest soil based Paenibacillus elgii
      and optimization of various culture conditions for its improved antimicrobial
      activity.
AB  - [This retracts the article on p. 1167 in vol. 6, PMID: 26539188.].

PMID- 29180995
TI  - B Cell Intrinsic Mechanisms Constraining IgE Memory.
AB  - Memory B cells and long-lived plasma cells are key elements of adaptive humoral
      immunity. Regardless of the immunoglobulin class produced, these cells can ensure
      long-lasting protection but also long-lasting immunopathology, thus requiring
      tight regulation of their generation and survival. Among all antibody classes,
      this is especially true for IgE, which stands as the most potent, and can trigger
      dramatic inflammatory reactions even when present in minute amounts. IgE
      responses and memory crucially protect against parasites and toxic components of
      venoms, conferring selective advantages and explaining their conservation in all
      mammalian species despite a parallel broad spectrum of IgE-mediated
      immunopathology. Long-term memory of sensitization and anaphylactic responses to
      allergens constitute the dark side of IgE responses, which can trigger multiple
      acute or chronic pathologic manifestations, some punctuated with life-threatening
      events. This Janus face of the IgE response and memory, both necessary and
      potentially dangerous, thus obviously deserves the most elaborated self-control
      schemes.

PMID- 29180996
TI  - Antibody Heavy Chain Variable Domains of Different Germline Gene Origins
      Diversify through Different Paths.
AB  - B cells produce antibodies, key effector molecules in health and disease. They
      mature their properties, including their affinity for antigen, through
      hypermutation events; processes that involve, e.g., base substitution, codon
      insertion and deletion, often in association with an isotype switch.
      Investigations of antibody evolution define modes whereby particular antibody
      responses are able to form, and such studies provide insight important for
      instance for development of efficient vaccines. Antibody evolution is also used
      in vitro for the design of antibodies with improved properties. To better
      understand the basic concepts of antibody evolution, we analyzed the mutational
      paths, both in terms of amino acid substitution and insertions and deletions,
      taken by antibodies of the IgG isotype. The analysis focused on the evolution of
      the heavy chain variable domain of sets of antibodies, each with an origin in 1
      of 11 different germline genes representing six human heavy chain germline gene
      subgroups. Investigated genes were isolated from cells of human bone marrow, a
      major site of antibody production, and characterized by next-generation
      sequencing and an in-house bioinformatics pipeline. Apart from substitutions
      within the complementarity determining regions, multiple framework residues
      including those in protein cores were targets of extensive diversification.
      Diversity, both in terms of substitutions, and insertions and deletions, in
      antibodies is focused to different positions in the sequence in a germline gene
      unique manner. Altogether, our findings create a framework for understanding
      patterns of evolution of antibodies from defined germline genes.

PMID- 29180998
TI  - Cystatin F Affects Natural Killer Cell Cytotoxicity.
AB  - Cystatin F is a cysteine peptidase inhibitor which, unlike other cystatin family
      members, is targeted to endosomal/lysosomal compartments. It is synthesized as an
      inactive disulfide-linked dimer which is then converted to an active monomer by
      proteolytic cleavage of 15 N-terminal residues. Cystatin F has been suggested to
      regulate the cytotoxicity of natural killer (NK) cells by inhibiting the major
      granzyme convertases, cathepsins C and H. To test this hypothesis, we prepared
      variants of cystatin F and analyzed their uptake, subcellular trafficking, and
      peptidase inhibition, as well as their impact on the cytotoxicity of NK-92 cells
      and primary NK cells. The N-glycosylation pattern is responsible for the
      secretion, uptake, and subcellular sorting of cystatin F in HeLa and Hek293
      cells, whereas the legumain binding site had no effect on these processes.
      Active, N-terminally truncated, monomeric cystatin F can also be internalized by
      recipient cells and targeted to endo/lysosomes, affecting also cells lacking the
      activating peptidase. Cystatin F mutants capable of cell internalization and
      trafficking through the endo/lysosomal pathway significantly decreased cathepsin
      C and H activities, both in situ, following transfection and in trans, using
      conditioned media. Further, incubation of IL-2 stimulated NK-92 and primary NK
      cells with full-length and N-terminally truncated cystatin F mutants led to
      suppression of their granule-mediated cytotoxicity. This effect was most
      significant with the N-terminally truncated mutants. These results suggest that
      cystatin F can be an important mediator within tumor microenvironment affecting
      the cytotoxicity of NK cells and consequently antitumor immune response.

PMID- 29180997
TI  - Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females
      Contribute to Sex-Related Differences in the Innate Immune Response.
AB  - Females have a longer lifespan and better general health than males. Considerable
      number of studies also demonstrated that, after trauma and sepsis, females
      present better outcomes as compared to males indicating sex-related differences
      in the innate immune response. The current notion is that differences in the
      immuno-modulatory effects of sex hormones are the underlying causative mechanism.
      However, the field remains controversial and the exclusive role of sex hormones
      has been challenged. Here, we propose that polymorphic X-linked immune competent
      genes, which are abundant in the population are important players in sex-based
      immuno-modulation and play a key role in causing sex-related outcome differences
      following trauma or sepsis. We describe the differences in X chromosome (ChrX)
      regulation between males and females and its consequences in the context of
      common X-linked polymorphisms at the individual as well as population level. We
      also discuss the potential pathophysiological and immune-modulatory aspects of
      ChrX cellular mosaicism, which is unique to females and how this may contribute
      to sex-biased immune-modulation. The potential confounding effects of ChrX
      skewing of cell progenitors at the bone marrow is also presented together with
      aspects of acute trauma-induced de novo ChrX skewing at the periphery. In support
      of the hypothesis, novel observations indicating ChrX skewing in a female trauma
      cohort as well as case studies depicting the temporal relationship between trauma
      induced cellular skewing and the clinical course are also described. Finally, we
      list and discuss a selected set of polymorphic X-linked genes, which are frequent
      in the population and have key regulatory or metabolic functions in the innate
      immune response and, therefore, are primary candidates for mediating sex-biased
      immune responses. We conclude that sex-related differences in a variety of
      disease processes including the innate inflammatory response to injury and
      infection may be related to the abundance of X-linked polymorphic immune
      competent genes, differences in ChrX regulation, and inheritance patterns between
      the sexes and the presence of X-linked cellular mosaicism, which is unique to
      females.

PMID- 29180999
TI  - Alarmin S100A8 Activates Alveolar Epithelial Cells in the Context of Acute Lung
      Injury in a TLR4-Dependent Manner.
AB  - Alveolar epithelial cells (AECs) are an essential part of the respiratory barrier
      in lungs for gas exchange and protection against pathogens. Damage to AECs occurs
      during lung injury and PAMPs/DAMPs have been shown to activate AECs. However,
      their interplay as well as the mechanism of AECs' activation especially by the
      alarmin S100A8/A9 is unknown. Thus, our aim was to study the mechanism of
      activation of AECs (type I and type II) by S100A8 and/or lipopolysaccharide (LPS)
      and to understand the role of endogenous S100A8/A9 in neutrophil recruitment in
      the lung. For our studies, we modified a previous protocol for isolation and
      culturing of murine AECs. Next, we stimulated the cells with S100A8 and/or LPS
      and analyzed cytokine/chemokine release. We also analyzed the contribution of the
      known S100-receptors TLR4 and RAGE in AEC activation. In a murine model of lung
      injury, we investigated the role of S100A8/A9 in neutrophil recruitment to lungs.
      S100A8 activates type I and type II cells in a dose- and time-dependent manner
      which could be quantified by the release of IL-6, KC, and MCP-1. We here clearly
      demonstrate that AEC s are activated by S100A8 via a TLR4-dependent pathway.
      Surprisingly, RAGE, albeit mainly expressed in lung tissue, plays no role.
      Additionally, we show that S100A8/A9 is an essential factor for neutrophil
      recruitment to lungs. We, therefore, conclude that S100A8 promotes acute lung
      injury via Toll-like receptor 4-dependent activation of AECs.

PMID- 29181000
TI  - Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor
      Repertoire Influencing Development of Autoimmunity.
AB  - Prenatal glucocorticoids are routinely administered to pregnant women at risk of
      preterm delivery in order to improve survival of the newborn. However, in half of
      the cases, birth occurs outside the beneficial period for lung development.
      Glucocorticoids are potent immune modulators and cause apoptotic death of
      immature T cells, and we have previously shown that prenatal betamethasone
      treatment at doses eliciting lung maturation induce profound thymocyte apoptosis
      in the offspring. Here, we asked if there are long-term consequences on the
      offspring's immunity after this treatment. In the non-obese diabetic mouse model,
      prenatal betamethasone clearly decreased the frequency of pathogenic T cells and
      the incidence of type 1 diabetes (T1D). In contrast, in the lupus-prone MRL/lpr
      strain, prenatal glucocorticoids induced changes in the T cell repertoire that
      resulted in more autoreactive cells. Even though glucocorticoids transiently
      enhanced regulatory T cell (Treg) development, these cells did not have a
      protective effect in a model for multiple sclerosis which relies on a limited
      repertoire of pathogenic T cells for disease induction that were not affected by
      prenatal betamethasone. We conclude that prenatal steroid treatment, by inducing
      changes in the T cell receptor repertoire, has unforeseeable consequences on
      development of autoimmune disease. Our data should encourage further research to
      fully understand the consequences of this widely used treatment.

PMID- 29181001
TI  - Disease Tolerance Mediated by Phosphorylated Indoleamine-2,3 Dioxygenase Confers
      Resistance to a Primary Fungal Pathogen.
AB  - Resistance to primary fungal pathogens is usually attributed to the
      proinflammatory mechanisms of immunity conferred by interferon-gamma activation
      of phagocytes that control microbial growth, whereas susceptibility is attributed
      to anti-inflammatory responses that deactivate immunity. This study challenges
      this paradigm by demonstrating that resistance to a primary fungal pathogen such
      as Paracoccidiodes brasiliensis can be mediated by disease tolerance, a mechanism
      that preserves host fitness instead of pathogen clearance. Among the mechanisms
      of disease tolerance described, a crucial role has been ascribed to the enzyme
      indoleamine-2,3 dioxygenase (IDO) that concomitantly controls pathogen growth by
      limiting tryptophan availability and reduces tissue damage by decreasing the
      inflammatory process. Here, we demonstrated in a pulmonary model of
      paracoccidioidomycosis that IDO exerts a dual function depending on the resistant
      pattern of hosts. IDO activity is predominantly enzymatic and induced by IFN
      gamma signaling in the pulmonary dendritic cells (DCs) from infected susceptible
      (B10.A) mice, whereas phosphorylated IDO (pIDO) triggered by TGF-beta activation
      of DCs functions as a signaling molecule in resistant mice. IFN-gamma signaling
      activates the canonical pathway of NF-kappaB that promotes a proinflammatory
      phenotype in B10.A DCs that control fungal growth but ultimately suppress T cell
      responses. In contrast, in A/J DCs IDO promotes a tolerogenic phenotype that
      conditions a sustained synthesis of TGF-beta and expansion of regulatory T cells
      that avoid excessive inflammation and tissue damage contributing to host fitness.
      Therefore, susceptibility is unexpectedly mediated by mechanisms of
      proinflammatory immunity that are usually associated with resistance, whereas
      genetic resistance is based on mechanisms of disease tolerance mediated by pIDO,
      a phenomenon never described in the protective immunity against primary fungal
      pathogens.

PMID- 29181002
TI  - The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in
      Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial.
AB  - Introduction: Aside from direct effects on neurotransmission, inhaled and
      intravenous anesthetics have immunomodulatory properties. In vitro and mouse
      model studies suggest that propofol inhibits, while isoflurane increases,
      neuroinflammation. If these findings translate to humans, they could be
      clinically important since neuroinflammation has detrimental effects on
      neurocognitive function in numerous disease states. Materials and methods: To
      examine whether propofol and isoflurane differentially modulate neuroinflammation
      in humans, cytokines were measured in a secondary analysis of cerebrospinal fluid
      (CSF) samples from patients prospectively randomized to receive anesthetic
      maintenance with propofol vs. isoflurane (registered with
      http://www.clinicaltrials.gov, identifier NCT01640275). We measured CSF levels of
      EGF, eotaxin, G-CSF, GM-CSF, IFN-alpha2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10,
      MCP-1, MIP-1alpha, MIP-1beta, and TNF-alpha before and 24 h after intracranial
      surgery in these study patients. Results: After Bonferroni correction for
      multiple comparisons, we found significant increases from before to 24 h after
      surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1alpha, MIP-1beta,
      and TNF-alpha. However, we found no difference in cytokine levels at baseline or
      24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21)
      patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and
      MCP-1 levels directly correlated with each other and with postoperative CSF
      elevations in tau, a neural injury biomarker. We observed CSF cytokine increases
      up to 10-fold higher after intracranial surgery than previously reported after
      other types of surgery. Discussion: These data clarify the magnitude of
      neuroinflammation after intracranial surgery, and raise the possibility that a
      coordinated neuroinflammatory response may play a role in neural injury after
      surgery.

PMID- 29181003
TI  - The Human-Associated Archaeon Methanosphaera stadtmanae Is Recognized through Its
      RNA and Induces TLR8-Dependent NLRP3 Inflammasome Activation.
AB  - The archaeon Methanosphaera stadtmanae is a member of the gut microbiota; yet,
      the molecular cross-talk between archaea and the human immune system and its
      potential contribution to inflammatory diseases has not been evaluated. Although
      archaea are as bacteria prokaryotes, they form a distinct domain having unique
      features such as different cell wall structures and membrane lipids. So far, no
      microbe-associated molecular patterns of archaea which activate innate immune
      receptors have been identified. By stimulating human myeloid cells with M.
      stadtmanae and purified archaeal nucleic acids, we identified both the
      microorganism and its RNA as potent stimuli for the innate immune system. To
      dissect the recognition and activation pathways induced by M. stadtmanae, human
      monocytic BLaER1 knockout cells were generated using the CRISPR/Cas9 system
      targeting components of TLR and inflammasome signaling. While the recognition of
      M. stadtmanae is mediated by TLR7 and TLR8, activation of the NLRP3 inflammasome
      depends solely on TLR8 engagement. Notably, this process resembles hallmarks of
      both the canonical and the recently described alternative inflammasome
      activation. Thus, we have demonstrated for the first time the specific
      recognition of and response to an archaeon by human cells at the molecular level.

PMID- 29181004
TI  - Identification of Secretory Leukoprotease Inhibitor As an Endogenous Negative
      Regulator in Allergic Effector Cells.
AB  - Mast cells, basophils, and eosinophils are central effectors in allergic
      inflammatory disorders. These cells secrete abundant serine proteases as well as
      chemical mediators and cytokines; however, the expression profiles and functions
      of their endogenous inhibitors remain elusive. We found that murine secretory
      leukoprotease inhibitor (SLPI) is expressed in basophils and eosinophils but in
      not in mast cells. SLPI-deficient (Slpi-/-) basophils produce more cytokines than
      wild-type mice after IgE stimulation. Although the deletion of SLPI in basophils
      did not affect the release of chemical mediators upon IgE stimulation, the
      enzymatic activity of the serine protease tryptase was increased in Slpi-/-
      basophils. Mice transferred with Slpi-/- basophils were highly sensitive to IgE
      mediated chronic allergic inflammation. Eosinophils lacking SLPI showed greater
      interleukin-6 secretion and invasive activity upon lipopolysaccharide
      stimulation, and the expression of matrix metalloproteinase-9 by these
      eosinophils was increased without stimulation. The absence of SLPI increases JNK1
      phosphorylation at the steady state, and augments the serine phosphorylation of
      JNK1-downstream ETS transcriptional factor Elk-1 in eosinophils upon stimulation.
      Of note, SLPI interacts with a scaffold protein, JNK-interacting protein 3
      (JIP3), that constitutively binds to the cytoplasmic domain of toll-like receptor
      (TLR) 4, suggesting that SLPI controls Elk-1 activation via binding to JIP3 in
      eosinophils. Mice transferred with Slpi-/- eosinophils showed the exacerbation of
      chitin-induced allergic inflammation. These findings showed that SLPI is a
      negative regulator in allergic effector cells and suggested a novel inhibitory
      role of SLPI in the TLR4 signaling pathways.

PMID- 29181005
TI  - Induction of Robust B Cell Responses after Influenza mRNA Vaccination Is
      Accompanied by Circulating Hemagglutinin-Specific ICOS+ PD-1+ CXCR3+ T Follicular
      Helper Cells.
AB  - Modified mRNA vaccines have developed into an effective and well-tolerated
      vaccine platform that offers scalable and precise antigen production.
      Nevertheless, the immunological events leading to strong antibody responses
      elicited by mRNA vaccines are largely unknown. In this study, we demonstrate that
      protective levels of antibodies to hemagglutinin were induced after two
      immunizations of modified non-replicating mRNA encoding influenza H10
      encapsulated in lipid nanoparticles (LNP) in non-human primates. While both
      intradermal (ID) and intramuscular (IM) administration induced protective titers,
      ID delivery generated this response more rapidly. Circulating H10-specific memory
      B cells expanded after each immunization, along with a transient appearance of
      plasmablasts. The memory B cell pool waned over time but remained detectable
      throughout the 25-week study. Following prime immunization, H10-specific plasma
      cells were found in the bone marrow and persisted over time. Germinal centers
      were formed in vaccine-draining lymph nodes along with an increase in circulating
      H10-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells, a population shown to
      correlate with high avidity antibody responses after seasonal influenza
      vaccination in humans. Collectively, this study demonstrates that mRNA/LNP
      vaccines potently induce an immunological repertoire associated with the
      generation of high magnitude and quality antibodies.

PMID- 29181006
TI  - Protective Effect of Panax notoginseng Root Water Extract against Influenza A
      Virus Infection by Enhancing Antiviral Interferon-Mediated Immune Responses and
      Natural Killer Cell Activity.
AB  - Influenza is an acute respiratory illness caused by the influenza A virus, which
      causes economic losses and social disruption mainly by increasing hospitalization
      and mortality rates among the elderly and people with chronic diseases. Influenza
      vaccines are the most effective means of preventing seasonal influenza, but can
      be completely ineffective if there is an antigenic mismatch between the seasonal
      vaccine virus and the virus circulating in the community. In addition, influenza
      viruses resistant to antiviral drugs are emerging worldwide. Thus, there is an
      urgent need to develop new vaccines and antiviral drugs against these viruses. In
      this study, we conducted in vitro and in vivo analyses of the antiviral effect of
      Panax notoginseng root (PNR), which is used as an herbal medicine and nutritional
      supplement in Korea and China. We confirmed that PNR significantly prevented
      influenza virus infection in a concentration-dependent manner in mouse
      macrophages. In addition, PNR pretreatment inhibited viral protein (PB1, PB2, HA,
      NA, M1, PA, M2, and NP) and viral mRNA (NS1, HA, PB2, PA, NP, M1, and M2)
      expression. PNR pretreatment also increased the secretion of pro-inflammatory
      cytokines [tumor necrosis factor alpha and interleukin 6] and interferon (IFN)
      beta and the phosphorylation of type-I IFN-related proteins (TANK-binding kinase
      1, STAT1, and IRF3) in vitro. In mice exposed to the influenza A H1N1 virus, PNR
      treatment decreased mortality by 90% and prevented weight loss (by approximately
      10%) compared with the findings in untreated animals. In addition, splenocytes
      from PNR-administered mice displayed significantly enhanced natural killer (NK)
      cell activity against YAC-1 cells. Taking these findings together, PNR stimulates
      an antiviral response in murine macrophages and mice that protects against viral
      infection, which may be attributable to its ability to stimulate NK cell
      activity. Further investigations are needed to reveal the molecular mechanisms
      underlying the protective effects of PNR and its components against influenza
      virus A infection.

PMID- 29181008
TI  - Engineered Soluble Monomeric IgG1 Fc with Significantly Decreased Non-Specific
      Binding.
AB  - Due to the long serum half-life provided by the neonatal Fc receptor (FcRn)
      recycling, the IgG1 Fc has been pursued as the fusion partner to develop
      therapeutic Fc-fusion proteins, or as the antibody-derived scaffold that could be
      engineered with antigen-binding capabilities. In previous studies, we engineered
      the monomeric Fc by mutating critical residues located on the IgG1 Fc
      dimerization interface. Comparing with the wild-type dimeric Fc, monomeric Fc
      might possess substantial advantages conferred by its smaller size, but also
      suffers the disadvantage of non-specific binding to some unrelated antigens,
      raising considerable concerns over its potential clinical development. Here, we
      describe a phage display-based strategy to examine the effects of multiple
      mutations of IgG1 monomeric Fc and, simultaneously, to identify new Fc monomers
      with desired properties. Consequently, we identified a novel monomeric Fc that
      displayed significantly decreased non-specificity. In addition, it exhibited
      higher thermal stability and comparable pH-dependent FcRn binding to the previous
      reported monomeric Fc. These results provide baseline to understand the mechanism
      underlying the generation of soluble IgG1 Fc monomers and warrant the further
      clinical development of monomeric Fc-based fusion proteins as well as antigen
      binders.

PMID- 29181009
TI  - CRISPRi Induced Suppression of Fimbriae Gene (fimH) of a Uropathogenic
      Escherichia coli: An Approach to Inhibit Microbial Biofilms.
AB  - Urinary tract infection (UTI) is one the common infections caused by the
      recalcitrant nature of biofilms, developed after the pathogen has adhered to the
      inner lining of the urinary tract. Although significant research has been made in
      recent years to control these types of infection, but as of yet, no approach has
      sufficiently been able to reduce the prevalence of UTIs. The main objective of
      this study was to prevent UTIs through targeting the fimH gene, which is the
      major virulent factor responsible for biofilm formation. The novelty of this work
      lies in the use of CRISPRi, a gene specific editing tool to control such types of
      infections. Accordingly, the system was designed to target fimH gene, responsible
      for bacterial adherence and this approach was successfully validated by
      performing microscopic, biofilm and adherence assays.

PMID- 29181007
TI  - Interplay between Natural Killer Cells and Anti-HER2 Antibodies: Perspectives for
      Breast Cancer Immunotherapy.
AB  - Overexpression of the human epidermal growth factor receptor 2 (HER2) defines a
      subgroup of breast tumors with aggressive behavior. The addition of HER2-targeted
      antibodies (i.e., trastuzumab, pertuzumab) to chemotherapy significantly improves
      relapse-free and overall survival in patients with early-stage and advanced
      disease. Nonetheless, considerable proportions of patients develop resistance to
      treatment, highlighting the need for additional and co-adjuvant therapeutic
      strategies. HER2-specific antibodies can trigger natural killer (NK) cell
      mediated antibody-dependent cellular cytotoxicity and indirectly enhance the
      development of tumor-specific T cell immunity; both mechanisms contributing to
      their antitumor efficacy in preclinical models. Antibody-dependent NK cell
      activation results in the release of cytotoxic granules as well as the secretion
      of pro-inflammatory cytokines (i.e., IFNgamma and TNFalpha) and chemokines.
      Hence, NK cell tumor suppressive functions include direct cytolytic killing of
      tumor cells as well as the regulation of subsequent antitumor adaptive immunity.
      Albeit tumors with gene expression signatures associated to the presence of
      cytotoxic lymphocyte infiltrates benefit from trastuzumab-based treatment, NK
      cell-related biomarkers of response/resistance to HER2-specific therapeutic
      antibodies in breast cancer patients remain elusive. Several variables, including
      (i) the configuration of the patient NK cell repertoire; (ii) tumor molecular
      features (i.e., estrogen receptor expression); (iii) concomitant therapeutic
      regimens (i.e., chemotherapeutic agents, tyrosine kinase inhibitors); and (iv)
      evasion mechanisms developed by progressive breast tumors, have been shown to
      quantitatively and qualitatively influence antibody-triggered NK cell responses.
      In this review, we discuss possible interventions for restoring/enhancing the
      therapeutic activity of HER2 therapeutic antibodies by harnessing NK cell
      antitumor potential through combinatorial approaches, including immune checkpoint
      blocking/stimulatory antibodies, cytokines and toll-like receptor agonists.

PMID- 29181011
TI  - From IgG Fusion Proteins to Engineered-Specific Human Regulatory T Cells: A Life
      of Tolerance.
AB  - Recent efforts have concentrated on approaches to expand and "specify" human
      regulatory T cells (Tregs) and to apply them to modulate adverse immune responses
      in autoimmunity and hemophilia. We have used retroviral transduction of specific
      T-cell receptor, single chain Fv, or antigen domains in Tregs to achieve this
      goal. Each of these approaches have advantages and disadvantages. Results with
      these engineered T cells and evolution of the research developments and paths
      that led to the development of specific regulatory approaches for tolerance are
      summarized.

PMID- 29181010
TI  - Crystallizable Fragment Glycoengineering for Therapeutic Antibodies Development.
AB  - Monoclonal antibody (mAb)-based therapeutics are the fastest growing class of
      human pharmaceuticals. They are typically IgG1 molecules with N-glycans attached
      to the N297 residue on crystallizable fragment (Fc). Different Fc glycoforms
      impact their effector function, pharmacokinetics, stability, aggregation, safety,
      and immunogenicity. Fc glycoforms affect mAbs effector functions including
      antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent
      cytotoxicity (CDC) by modulating the Fc-FcgammaRs and Fc-C1q interactions. While
      the terminal galactose enhances CDC activity, the fucose significantly decreases
      ADCC. Defucosylated immunoglobulin Gs (IgGs) are thus highly pursued as next
      generation therapeutic mAbs with potent ADCC at reduced doses. A plethora of cell
      glycoengineering and chemoenzymatic glycoengineering strategies is emerging to
      produce IgGs with homogenous glycoforms especially without core fucose. The
      chemoenzymatic glycosylation remodeling also offers useful avenues for site
      specific conjugations of small molecule drugs onto mAbs. Herein, we review the
      current progress of IgG-Fc glycoengineering. We begin with the discussion of the
      structures of IgG N-glycans and biosynthesis followed by reviewing the impact of
      IgG glycoforms on antibody effector functions and the current Fc glycoengineering
      strategies with emphasis on Fc defucosylation. Furthermore, we briefly discuss
      two novel therapeutic mAbs formats: aglycosylated mAbs and Fc glycan specific
      antibody-drug conjugates (ADCs). The advances in the understanding of Fc
      glycobiology and development of novel glycoengineering technologies have
      facilitated the generation of therapeutic mAbs with homogenous glycoforms and
      improved therapeutic efficacy.

PMID- 29181012
TI  - Sulfated Polysaccharides in the Freshwater Green Macroalga Cladophora surera Not
      Linked to Salinity Adaptation.
AB  - The presence of sulfated polysaccharides in cell walls of seaweeds is considered
      to be a consequence of the physiological adaptation to the high salinity of the
      marine environment. Recently, it was found that sulfated polysaccharides were
      present in certain freshwater Cladophora species and some vascular plants.
      Cladophora (Ulvophyceae, Chlorophyta) is one of the largest genera of green algae
      that are able to grow in both, seas and freshwater courses. Previous studies
      carried out on the water-soluble polysaccharides of the marine species C.
      falklandica established the presence of sulfated xylogalactoarabinans constituted
      by a backbone of 4-linked beta-L-arabinopyranose units partially sulfated mainly
      on C3 and also on C2 with partial glycosylation, mostly on C2, with terminal beta
      D-xylopyranose or beta-D-galactofuranose units. Besides, minor amounts of 3-, 6-
      and/or 3,6-linked beta-D-galactan structures, with galactose in the pyranosic
      form were detected. In this work, the main water soluble cell wall
      polysaccharides from the freshwater alga Cladophora surera were characterized. It
      was found that this green alga biosynthesizes sulfated polysaccharides, with a
      structure similar to those found in marine species of this genus. Calibration of
      molecular clock with fossil data suggests that colonization of freshwater
      environments occurred during the Miocene by its ancestor. Therefore, the presence
      of sulfated polysaccharides in the freshwater green macroalga C. surera could be,
      in this case, an adaptation to transient desiccation and changes in ionic
      strength. Retention of sulfated polysaccharides at the cell walls may represent a
      snapshot of an evolutionary event, and, thus constitutes an excellent model for
      further studies on the mechanisms of sulfation on cell wall polysaccharides and
      environmental stress co-evolution.

PMID- 29181013
TI  - Abiotic Stresses Cause Differential Regulation of Alternative Splice Forms of
      GATA Transcription Factor in Rice.
AB  - The GATA gene family is one of the most conserved families of transcription
      factors, playing a significant role in different aspects of cellular processes,
      in organisms ranging from fungi to angiosperms. GATA transcription factors are
      DNA-binding proteins, having a class IV zinc-finger motif CX2CX17-20CX2C followed
      by a highly basic region and are known to bind a consensus sequence WGATAR. In
      plants, GATAs are known to be involved in light-dependent gene regulation and
      nitrate assimilation. However, a comprehensive analysis of these GATA gene
      members has not yet been highlighted in rice when subjected to environmental
      stresses. In this study, we present an overview of the GATA gene family in rice
      (OsGATA) in terms of, their chromosomal distribution, domain architecture, and
      phylogeny. Our study has revealed the presence of 28 genes, encoding 35 putative
      GATA transcription factors belonging to seven subfamilies in the rice genome.
      Transcript abundance analysis in contrasting genotypes of rice-IR64 (salt
      sensitive) and Pokkali (salt tolerant), for individual GATA members indicated
      their differential expression in response to various abiotic stresses such as
      salinity, drought, and exogenous ABA. One of the members of subfamily VII
      OsGATA23a, emerged as a multi-stress responsive transcription factor giving
      elevated expression levels in response to salinity and drought. ABA also induces
      expression of OsGATA23a by 35 and 55-folds in IR64 and Pokkali respectively.
      However, OsGATA23b, an alternative splice variant of OsGATA23 did not respond to
      above-mentioned stresses. Developmental regulation of the OsGATA genes based on a
      publicly available microarray database showed distinct expression patterns for
      most of the GATA members throughout different stages of rice development.
      Altogether, our results suggest inherent roles of diverse OsGATA factors in
      abiotic stress signaling and also throw some light on the tight regulation of the
      spliced variants of OsGATA genes in response to different environmental
      conditions.

PMID- 29181014
TI  - Inspecting the True Identity of Herbal Materials from Cynanchum Using ITS2
      Barcode.
AB  - Cynanchum is a large genus with some important medicinal species in China. The
      medicinal species in Cynanchum are easily confused, leading to potential safety
      risks. In this study, the internal transcribed spacer 2 (ITS2) barcode was used
      to discriminate the medicinal plants in Cynanchum. The identifying capability of
      ITS2 was assessed using the specific genetic divergence, BLAST1, neighbor-joining
      (NJ) tree, maximum-likelihood (ML) tree, and single-nucleotide polymorphism (SNP)
      methods. Results indicated that the intra-specific genetic divergences of
      Cynanchum species were lower than their inter-specific genetic divergences. Of
      the 87 samples from 17 species, ITS2 showed a high identification efficiency of
      90.8 and 87.4% at the species level through BLAST1 and the nearest distance
      methods. NJ tree and ML tree also demonstrated the suitability of ITS2 to
      differentiate Cynanchum species. Meanwhile, a stable SNP was found, and it could
      accurately authenticate Cynanchum paniculatum and Cynanchum atratum. Furthermore,
      we collected 64 commercial samples from three commonly used herbal medicines and
      evaluated the capability of ITS2 to survey their authentication. Of these
      samples, Cynanchi Atrati Radix et Rhizoma (Baiwei) showed a potential safety
      problem, and all the 11 test samples were adulterants. In conclusion, ITS2 can
      distinguish medicinal species in Cynanchum effectively, and its application could
      greatly improve the identification efficiency and accuracy of commercial herbal
      medicines in this genus.

PMID- 29181015
TI  - An Extended Approach to Quantify Triacylglycerol in Microalgae by Characteristic
      Fatty Acids.
AB  - Microalgae represent a third generation biofuel feedstock due to their high
      triacylglycerol (TAG) content under adverse environmental conditions. Microalgal
      TAG resides in a single cell and serves as a lipid class mixed with complicated
      compositions. We previously showed that TAG possessed characteristic fatty acids
      (CFAs) for quantification and was linearly correlated with the relative abundance
      of CFA within certain limits in microalgae. Here, we defined the application
      range of the linear correlation between TAG and CFA in the oleaginous microalgae
      Chlamydomonas reinhardtii and Phaeodactylum tricornutum. In addition, TAG
      quantification was further expanded to a wide range of levels and the absolute
      amounts of saturated or monounsaturated CFAs, 16:0 and 18:1n9 of C. reinhardtii
      and 16:0 and 16:1n7 of P. tricornutum, instead of polyunsaturated CFAs, were
      verified to be linearly correlated to TAG levels throughout the entire period of
      nitrogen stress. This approach utilizes a single fatty acid to quantify TAG
      mixtures, and is rapid, simple and precise, which provides a useful tool for
      monitoring TAG accumulation of distinct microalgal species and facilitating high
      throughput mutant screening for microalgae.

PMID- 29181016
TI  - The Biosynthesis of Unusual Floral Volatiles and Blends Involved in Orchid
      Pollination by Deception: Current Progress and Future Prospects.
AB  - Flowers have evolved diverse strategies to attract animal pollinators, with
      visual and olfactory floral cues often crucial for pollinator attraction. While
      most plants provide reward (e.g., nectar, pollen) in return for the service of
      pollination, 1000s of plant species, particularly in the orchid family, offer no
      apparent reward. Instead, they exploit their often specific pollinators (one or
      few) by mimicking signals of female insects, food source, and oviposition sites,
      among others. A full understanding of how these deceptive pollination strategies
      evolve and persist remains an open question. Nonetheless, there is growing
      evidence that unique blends that often contain unusual compounds in floral
      volatile constituents are often employed to secure pollination by deception.
      Thus, the ability of plants to rapidly evolve new pathways for synthesizing
      floral volatiles may hold the key to the widespread evolution of deceptive
      pollination. Yet, until now the biosynthesis of these volatile compounds has been
      largely neglected. While elucidating the biosynthesis in non-model systems is
      challenging, nonetheless, these cases may also offer untapped potential for
      biosynthetic breakthroughs given that some of the compounds can be exclusive or
      dominant components of the floral scent and production is often tissue-specific.
      In this perspective article, we first highlight the chemical diversity
      underpinning some of the more widespread deceptive orchid pollination strategies.
      Next, we explore the potential metabolic pathways and biosynthetic steps that
      might be involved. Finally, we offer recommendations to accelerate the discovery
      of the biochemical pathways in these challenging but intriguing systems.

PMID- 29181017
TI  - Alternate Modes of Photosynthate Transport in the Alternating Generations of
      Physcomitrella patens.
AB  - Physcomitrella patens has emerged as a model moss system to investigate the
      evolution of various plant characters in early land plant lineages. Yet, there is
      merely a disparate body of ultrastructural and physiological evidence from other
      mosses to draw inferences about the modes of photosynthate transport in the
      alternating generations of Physcomitrella. We performed a series of
      ultrastructural, fluorescent tracing, physiological, and immunohistochemical
      experiments to elucidate a coherent model of photosynthate transport in this
      moss. Our ultrastructural observations revealed that Physcomitrella is an
      endohydric moss with water-conducting and putative food-conducting cells in the
      gametophytic stem and leaves. Movement of fluorescent tracer 5(6)
      carboxyfluorescein diacetate revealed that the mode of transport in the
      gametophytic generation is symplasmic and is mediated by plasmodesmata, while
      there is a diffusion barrier composed of transfer cells that separates the
      photoautotrophic gametophyte from the nutritionally dependent heterotrophic
      sporophyte. We posited that, analogous to what is found in apoplasmically phloem
      loading higher plants, the primary photosynthate sucrose, is actively imported
      into the transfer cells by sucrose/H+ symporters (SUTs) that are, in turn,
      powered by P-type ATPases, and that the transfer cells harbor an ATP-conserving
      Sucrose Synthase (SUS) pathway. Supporting our hypothesis was the finding that a
      protonophore (2,4-dinitrophenol) and a SUT-specific inhibitor (diethyl
      pyrocarbonate) reduced the uptake of radiolabeled sucrose into the sporangia. In
      situ immunolocalization of P-type ATPase, Sucrose Synthase, and Proton
      Pyrophosphatase - all key components of the SUS pathway - showed that these
      proteins were prominently localized in the transfer cells, providing further
      evidence consistent with our argument.

PMID- 29181018
TI  - Corrigendum: Phytohormone and Putative Defense Gene Expression Differentiates the
      Response of 'Hayward' Kiwifruit to Psa and Pfm Infections.
AB  - [This corrects the article on p. 1366 in vol. 8, PMID: 28824694.].

PMID- 29181020
TI  - Chaos Quantum-Behaved Cat Swarm Optimization Algorithm and Its Application in the
      PV MPPT.
AB  - Cat Swarm Optimization (CSO) algorithm was put forward in 2006. Despite a faster
      convergence speed compared with Particle Swarm Optimization (PSO) algorithm, the
      application of CSO is greatly limited by the drawback of "premature convergence,"
      that is, the possibility of trapping in local optimum when dealing with nonlinear
      optimization problem with a large number of local extreme values. In order to
      surmount the shortcomings of CSO, Chaos Quantum-behaved Cat Swarm Optimization
      (CQCSO) algorithm is proposed in this paper. Firstly, Quantum-behaved Cat Swarm
      Optimization (QCSO) algorithm improves the accuracy of the CSO algorithm, because
      it is easy to fall into the local optimum in the later stage. Chaos Quantum
      behaved Cat Swarm Optimization (CQCSO) algorithm is proposed by introducing tent
      map for jumping out of local optimum in this paper. Secondly, CQCSO has been
      applied in the simulation of five different test functions, showing higher
      accuracy and less time consumption than CSO and QCSO. Finally, photovoltaic MPPT
      model and experimental platform are established and global maximum power point
      tracking control strategy is achieved by CQCSO algorithm, the effectiveness and
      efficiency of which have been verified by both simulation and experiment.

PMID- 29181021
TI  - Mental Task Evaluation for Hybrid NIRS-EEG Brain-Computer Interfaces.
AB  - Based on recent electroencephalography (EEG) and near-infrared spectroscopy
      (NIRS) studies that showed that tasks such as motor imagery and mental arithmetic
      induce specific neural response patterns, we propose a hybrid brain-computer
      interface (hBCI) paradigm in which EEG and NIRS data are fused to improve binary
      classification performance. We recorded simultaneous NIRS-EEG data from nine
      participants performing seven mental tasks (word generation, mental rotation,
      subtraction, singing and navigation, and motor and face imagery). Classifiers
      were trained for each possible pair of tasks using (1) EEG features alone, (2)
      NIRS features alone, and (3) EEG and NIRS features combined, to identify the best
      task pairs and assess the usefulness of a multimodal approach. The NIRS-EEG
      approach led to an average increase in peak kappa of 0.03 when using features
      extracted from one-second windows (equivalent to an increase of 1.5% in
      classification accuracy for balanced classes). The increase was much stronger
      (0.20, corresponding to an 10% accuracy increase) when focusing on time windows
      of high NIRS performance. The EEG and NIRS analyses further unveiled relevant
      brain regions and important feature types. This work provides a basis for future
      NIRS-EEG hBCI studies aiming to improve classification performance toward more
      efficient and flexible BCIs.

PMID- 29181019
TI  - Crosstalk between the Androgen Receptor and PPAR Gamma Signaling Pathways in the
      Prostate.
AB  - Nuclear receptors are a superfamily of ligand-activated transcription factors
      that play critical roles in the regulation of normal biological processes and
      several disease states. Of the nuclear receptors expressed within the prostate,
      the androgen receptor (AR) promotes the differentiation of prostatic epithelial
      cells and stimulates production of enzymes needed for liquefaction of semen.
      Multiple forms of AR also promote the growth of both early and late stage
      prostate cancers. As a result, drugs that target the AR signaling pathway are
      routinely used to treat patients with advanced forms of prostate cancer. Data
      also suggest that a second member of the nuclear receptor superfamily, the
      peroxisome proliferator activated receptor gamma (PPARgamma), is a tumor
      suppressor that regulates growth of normal prostate and prostate cancers. Recent
      studies indicate there is a bidirectional interaction between AR and PPARgamma,
      with each receptor influencing the expression and/or activity of the other within
      prostatic tissues. In this review, we examine how AR and PPARgamma each regulate
      the growth and development of normal prostatic epithelial cells and prostate
      cancers. We also discuss interactions between the AR and PPARgamma signaling
      pathways and how those interactions may influence prostate biology.

PMID- 29181023
TI  - Corrigendum to "Suppressing Syndecan-1 Shedding Ameliorates Intestinal Epithelial
      Inflammation through Inhibiting NF-kappaB Pathway and TNF-alpha".
AB  - [This corrects the article DOI: 10.1155/2016/6421351.].

PMID- 29181022
TI  - First-Line Helicobacter pylori Eradication with Vonoprazan, Clarithromycin, and
      Metronidazole in Patients Allergic to Penicillin.
AB  - Aim: To assess the efficacy of 7-day first-line Helicobacter pylori eradication
      with vonoprazan (VPZ), clarithromycin (CAM), and metronidazole (MNZ) in patients
      with penicillin allergy. Methods: Patients with penicillin allergy, diagnosed
      with Helicobacter pylori infection and did not have history of Helicobacter
      pylori eradication, were eligible for the study. Twenty patients were
      prospectively treated with 20 mg VPZ twice daily, 200 or 400 mg CAM twice daily,
      and 250 mg MNZ twice daily for 7 days. We also collected the data from 30
      patients retrospectively treated with proton pump inhibitor (PPI), CAM, and MNZ.
      Safety was evaluated in patients completing an adverse effect questionnaire.
      Results: Both the intention-to-treat and per-protocol effectiveness of VPZ-based
      eradication were 100% (95% CI: 86.1-100%; n = 20). The eradication rates of PPI
      based regimen were 83.3% (95% CI: 65.3-94.4%) in the ITT and 82.7% (95% CI: 64.2
      94.2%) in the PP analyses. Abdominal fullness was more frequent in VCM compared
      to PCM. However, all patients with VCM regimen had taken 100% of their course of
      medication. Conclusion: Triple therapy with VPZ, CAM, and MNZ is well tolerated
      and effective for eradicating Helicobacter pylori in patients allergic to
      penicillin. This study was registered in the UMIN Clinical Trials Registry as
      UMIN000016335.

PMID- 29181024
TI  - Corrigendum to "Sugammadex-Enhanced Neuronal Apoptosis following Neonatal
      Sevoflurane Exposure in Mice".
AB  - [This corrects the article DOI: 10.1155/2016/9682703.].

PMID- 29181025
TI  - Detection of Bone Defects Using CBCT Exam in an Italian Population.
AB  - Background: The aim of this study was to evaluate the in vivo incidence and the
      location of fenestrations in a young Italian population by using CBCT. Materials
      and Methods: Fifty patients who had previously performed CBCT for planning third
      molar extraction or orthodontic therapy were selected for the study. No previous
      dental treatment had been performed on these patients. Overall, 1,395 teeth were
      evaluated. Root fenestrations were identified according to the definition of
      Davies and the American Association of Endodontists. Data was collected and
      statistically analyzed. Results: Fenestrations were observed in 159 teeth out of
      1,395 (11% of teeth). In the lower jaw, we found 68 fenestrations (5%) and 91 in
      the maxilla (6,5%). Incisors were the teeth with the highest incidence of
      fenestrations. Conclusion: The relative common finding (11%) of fenestration
      supports the need for CBCT exams before any surgical/implant treatment to avoid
      complications related to the initial presence of fenestrations. CBCT was found to
      be an effective and convenient tool for diagnosing fenestration.

PMID- 29181026
TI  - Simple Quantification of Pentosidine in Human Urine and Plasma by High
      Performance Liquid Chromatography.
AB  - Pentosidine is an advanced glycation end-product (AGE) and fluorescent cross-link
      compound. A simple high-performance liquid chromatographic (HPLC) method was
      developed for the detection and quantification of pentosidine in human urine and
      plasma. The mobile phase used a gradient system to improve separation of
      pentosidine from endogenous peaks, and chromatograms were monitored by
      fluorescent detector set at excitation and emission wavelengths of 328 and 378
      nm, respectively. The retention time for pentosidine was 24.3 min and the lower
      limits of quantification (LLOQ) in human urine and plasma were 1 nM. The intraday
      assay precisions (coefficients of variation) were generally low and found to be
      in the range of 5.19-7.49% and 4.96-8.78% for human urine and plasma,
      respectively. The corresponding values of the interday assay precisions were
      9.45% and 4.27%. Accuracies (relative errors) ranged from 87.9% to 115%.
      Pentosidine was stable in a range of pH solutions, human urine, and plasma. In
      summary, this HPLC method can be applied in future preclinical and clinical
      evaluation of pentosidine in the diabetic patients.

PMID- 29181027
TI  - Dispersive Solid Phase Extraction for the Analysis of Veterinary Drugs Applied to
      Food Samples: A Review.
AB  - To achieve analytical success, it is necessary to develop thorough clean-up
      procedures to extract analytes from the matrix. Dispersive solid phase extraction
      (DSPE) has been used as a pretreatment technique for the analysis of several
      compounds. This technique is based on the dispersion of a solid sorbent in liquid
      samples in the extraction isolation and clean-up of different analytes from
      complex matrices. DSPE has found a wide range of applications in several fields,
      and it is considered to be a selective, robust, and versatile technique. The
      applications of dispersive techniques in the analysis of veterinary drugs in
      different matrices involve magnetic sorbents, molecularly imprinted polymers,
      carbon-based nanomaterials, and the Quick, Easy, Cheap, Effective, Rugged, and
      Safe (QuEChERS) method. Techniques based on DSPE permit minimization of
      additional steps such as precipitation, centrifugation, and filtration, which
      decreases the manipulation of the sample. In this review, we describe the main
      procedures used for synthesis, characterization, and application of this
      pretreatment technique and how it has been applied to food analysis.

PMID- 29181028
TI  - Comparison of the Performance of Urinary Mycobacterium tuberculosis Antigens
      Cocktail (ESAT6, CFP10, and MPT64) with Culture and Microscopy in Pulmonary
      Tuberculosis Patients.
AB  - Pulmonary tuberculosis (TB) is a major global health problem and is one of the
      top 10 causes of death worldwide. Our study aimed to evaluate the performance of
      urinary Mycobacterium tuberculosis (Mtb) antigens cocktail (ESAT6, CFP10, and
      MPT64) compared with culture and microscopy. This descriptive cross-sectional
      study was conducted in Dr. Hasan Sadikin General Hospital, Bandung, from January
      2014 to October 2016. A total of 141 pulmonary tuberculosis patients were
      included. Sputum samples were examined for acid-fast bacilli (ZN stain) and
      mycobacterial culture (LJ); the Mtb antigens cocktail was examined in the urine
      sample. The positivity rate of TB detection from the three methods was as
      follows: AFB 52/141 (36.9%), culture 50/141 (35.5%), and urinary Mtb antigens
      cocktail 95/141 (67.4%). Sensitivity, specificity, PPV, and NPV of urinary Mtb
      antigens cocktail were 68.2%, 33%, 31.6%, and 69.6%, respectively. Validity of
      combination of both methods with culture as a gold standard yielded sensitivity,
      specificity, PPV, and NPV of 90%, 28.6%, 40.9%, and 83.8%, respectively.
      Combination of urinary Mtb antigens cocktail with AFB as a screening test gives a
      good sensitivity, although the specificity is reduced. Urinary Mtb antigens
      cocktail can be used as screening test for pulmonary tuberculosis.

PMID- 29181029
TI  - Incidence and Risk Factors for Infections Requiring Hospitalization, Including
      Pneumocystis Pneumonia, in Japanese Patients with Rheumatoid Arthritis.
AB  - Objective: Rheumatoid arthritis (RA) may be complicated by different infections,
      but risk factors for these are not fully elucidated. Here, we assessed the
      incidence of and risk factors for infections requiring hospitalization (IRH)
      including pneumocystis pneumonia (PCP) in patients with RA. Methods: We
      retrospectively surveyed all RA patients treated at our hospital from 2009 to
      2013, for whom data were available on demographic features, medications,
      comorbidities, and severity of RA. Multivariate logistic regression analysis was
      applied to calculate adjusted odds ratios (ORs) for factors associated with the
      occurrence of IRH. Results: In a total of 9210 patient-years (2688 patients),
      there were 373 IRH (3.7/100 patient-years). Respiratory tract infections were
      most frequent (n = 154, and additionally 16 PCP), followed by urinary tract
      infections (n = 50). Significant factors for PCP included higher age (>=70 years;
      OR 3.5), male sex (6.6), underlying lung disease (3.0), use of corticosteroids
      (4.8), and use of biologics (5.4). Use of methotrexate (5.7) was positively
      associated with PCP but negatively with total infections (0.7). Additionally,
      functional disorders and higher RA disease activity were also related to total
      infections. Conclusions: Risk factors for infection should be taken into account
      when deciding treatment for the individual RA patient.

PMID- 29181030
TI  - Recovery from Cogwheel Rigidity and Akinesia and Improvement in Vibration Sense
      and Olfactory Perception following Removal of an Epoxy-Oleic Acid DNA Adduct.
AB  - The epoxy fatty acid cis-12,13-epoxy-oleic acid, which acts as a DNA adduct, may
      be generated during long-term storage of many seed oils, including those used in
      cooking, with frying oils and fried foods being a major source in the modern
      human diet. Removal of this epoxy fatty acid from the locus of the N-formyl
      peptide receptors was associated with recovery from cogwheel rigidity and
      akinesia as well as with improvement in vibration sense and olfactory perception.

PMID- 29181031
TI  - Laparoscopic Supracervical Hysterectomy with In-Bag Morcellation in Very Large
      Uterus.
AB  - Laparoscopic supracervical hysterectomy (LASH) is a safe and fast minimally
      invasive approach in hysterectomy. In order to extract the uterine body from the
      abdominal cavity, one condition for LASH is the morcellation of the tissue. The
      intra-abdominal dissemination of benign and occult malignant uterine cells is a
      possible risk of this method, which can be avoided by the use of special bags for
      laparoscopic in-bag morcellation. We present a case of laparoscopic supracervical
      hysterectomy with in-bag morcellation in a uterus of more than 1400 g. and
      describe that this minimal-access surgery is safe and feasible even in very large
      uteri. This case report is registered in Research Registry under the UIN
      researchregistry1810.

PMID- 29181032
TI  - Overt Lower Gastrointestinal Bleeding and Pseudotumor: A Rare Presentation of
      Cytomegalovirus Infection.
AB  - Cytomegalovirus (CMV) is a ubiquitous organism which can infect multiple organs
      of the body. In an immunocompromised patient, it can have a myriad of
      gastrointestinal manifestations. We report a case of recurrent hematochezia and
      concomitant pseudotumor in an AIDS (acquired immunodeficiency syndrome) patient
      attributable to CMV infection. A 62-year-old man with a history of AIDS,
      noncompliant with highly active antiretroviral therapy (HAART), presented with
      bright red blood per rectum. Index colonoscopy showed presence of multiple
      ulcers, colonic stenosis, and mass-like appearing lesion. Biopsy confirmed CMV
      infection and ruled out malignancy. Cessation of dual antiplatelet therapy and
      compliance with HAART lead to clinical cessation of bleeding and endoscopic
      healing of ulcers with complete resolution of colon mass on follow-up
      colonoscopy.

PMID- 29181033
TI  - Insulin-Like Growth Factor Binding Protein-6 Alters Skeletal Muscle
      Differentiation of Human Mesenchymal Stem Cells.
AB  - Insulin-like growth factor binding protein-6 (IGFBP-6), the main regulator of
      insulin-like growth factor-2 (IGF-2), is a component of the stem cell niche in
      developing muscle cells. However, its role in muscle development has not been
      clearly defined. In this study, we investigated the role of IGFBP-6 in muscle
      commitment and differentiation of human mesenchymal stem cells derived from the
      placenta. We showed that placental mesenchymal stem cells (PMSCs) have the
      ability to differentiate into muscle cells when exposed to a specific culture
      medium by expressing muscle markers Pax3/7, MyoD, myogenin, and myosin heavy
      chain in a stage-dependent manner with the ultimate formation of multinucleated
      fibers and losing pluripotency-associated markers, OCT4 and SOX2. The addition of
      IGFBP-6 significantly increased pluripotency-associated markers as well as muscle
      differentiation markers at earlier time points, but the latter decreased with
      time. On the other hand, silencing IGFBP-6 decreased both pluripotent and
      differentiation markers at early time points. The levels of these markers
      increased as IGFBP-6 levels were restored. These findings indicate that IGFBP-6
      influences MSC pluripotency and myogenic differentiation, with more prominent
      effects observed at the beginning of the differentiation process before muscle
      commitment.

PMID- 29181034
TI  - FGF2 Attenuates Neural Cell Death via Suppressing Autophagy after Rat Mild
      Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) can lead to physical and cognitive deficits, which
      are caused by the secondary injury process. Effective pharmacotherapies for TBI
      patients are still lacking. Fibroblast growth factor-2 (FGF2) is an important
      neurotrophic factor that can stimulate neurogenesis and angiogenesis and has been
      shown to have neuroprotective effects after brain insults. Previous studies
      indicated that FGF2's neuroprotective effects might be related to its function of
      regulating autophagy. The present study investigated FGF2's beneficial effects in
      the early stage of rat mild TBI and the underlying mechanisms. One hundred and
      forty-four rats were used for creating controlled cortical impact (CCI) models to
      simulate the pathological damage after TBI. Our results indicated that
      pretreatment of FGF2 played a neuroprotective role in the early stage of rat mild
      TBI through alleviating brain edema, reducing neurological deficits, preventing
      tissue loss, and increasing the number of surviving neurons in injured cortex and
      the ipsilateral hippocampus. FGF2 could also protect cells from various forms of
      death such as apoptosis or necrosis through inhibition of autophagy. Finally,
      autophagy activator rapamycin could abolish the protective effects of FGF2. This
      study extended our understanding of FGF2's neuroprotective effects and shed
      lights on the pharmacological therapy after TBI.

PMID- 29181035
TI  - The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the
      Tumor Microenvironment Niche.
AB  - Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy,
      particularly for their antitumor effects. This cell population can be isolated
      from multiple tissue sources and also display an innate ability to home to areas
      of inflammation, such as tumors. Upon entry into the tumor microenvironment
      niche, MSCs promote or inhibit tumor progression by various mechanisms, largely
      through the release of soluble factors. These factors can be immunomodulatory by
      activating or inhibiting both the adaptive and innate immune responses. The
      mechanisms by which MSCs modulate the immune response are not well understood.
      Because of this, the relationship between MSCs and immune cells within the tumor
      microenvironment niche continues to be an active area of research in order to
      help explain the apparent contradictory findings currently available in the
      literature. The ongoing research aims to enhance the potential of MSCs in future
      therapeutic applications.

PMID- 29181036
TI  - Microarray Analysis Reveals a Potential Role of lncRNA Expression in 3,4
      Benzopyrene/Angiotensin II-Activated Macrophage in Abdominal Aortic Aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a fatal disease, and exposure to 3,4
      benzopyrene (Bap) is closely related to the development of AAA. We have found
      that Bap could impair the biological function of endothelial progenitor cells
      (EPCs), which are associated with the occurrence of AAA. We have also
      demonstrated that macrophage activation plays a key role in Bap-induced AAA, but
      the mechanism is unknown. Here, we used a mouse lncRNA array to investigate the
      expression signatures of lncRNAs and mRNAs in Bap-activated macrophage. A total
      of 457 lncRNAs and 219 mRNAs were found to be differentially expressed. The
      function of differential mRNAs was determined by pathway and Gene Ontology
      analysis. Eight pathways associated with inflammation were upregulated, and seven
      pathways including cell apoptosis were downregulated. It was worth noting that
      AGE-RAGE pathway, which was involved in Bap-induced EPC dysfunction, was
      significantly upregulated in Bap-activated macrophage and may contribute to AAA
      formation. Thus, lncRNAs may exert a key role in activated macrophages and
      intervene the core lncRNAs and may inhibit the occurrence of a series of cascade
      reactions in the macrophages, which may provide potential targets for AAA caused
      by smoking.

PMID- 29181037
TI  - The Burden and Trend of Blood-Borne Pathogens among Asymptomatic Adult Population
      in Akwatia: A Retrospective Study at the St. Dominic Hospital, Ghana.
AB  - Background: This study was aimed at evaluating the seroprevalence and trend of
      blood-borne pathogens (HIV, HCV, HBV, and Syphilis) among asymptomatic adults at
      Akwatia during a four-year period (2013-2016). Materials and Methods: The study
      was a retrospective analysis of secondary data of blood donors who visited the
      hospital from January 2013 to December 2016. Archival data from 11,436
      prospective donors was extracted. Data included age, sex, and place of residence
      as well as results of infectious markers (HIV, HBV, HCV, and Syphilis). Results:
      The prevalence of blood-borne pathogens in the donor population was 4.06%, 7.23%,
      5.81%, and 10.42% for HIV, HBV, HCV, and Syphilis infections, respectively. A
      significant decline in HBV and HCV infections was observed in the general donor
      population and across genders. HIV infection rate remained steady while Syphilis
      infections recorded a significantly increasing trend, peaking in the year 2015
      (14.20%). Age stratification in HBV infection was significant, peaking among age
      group 40-49 years (8.82%). Conclusion: Asymptomatic blood-borne pathogen burden
      was high among the adult population in Akwatia. Gender variations in HBV, HCV,
      and Syphilis infections in the cumulative four-year burden were observed.
      Awareness needs to be created, especially in the older generation.

PMID- 29181038
TI  - Implementing an Oxygen Supplementation and Monitoring Protocol on Inpatient
      Pediatric Bronchiolitis: An Exercise in Deimplementation.
AB  - Aim: Our goal in this study is to evaluate the effectiveness of our oxygen (O2)
      protocol to reduce length of stay (LOS) for children hospitalized with
      bronchiolitis. Methods: In this retrospective cohort study, the outcomes of
      children <= 24 months old that were admitted with bronchiolitis and placed on the
      O2 protocol were compared to historical controls. The primary outcome was
      hospital length of stay. Secondary outcomes were duration of O2 supplementation,
      rates of pediatric intensive care unit transfer, and readmission. Results: Groups
      were not significantly different in age, gender, and rates of respiratory
      distress score assessment. Significantly more severely ill patients were in the
      O2 protocol group. There were no significant differences between control and O2
      protocol groups with regard to mean LOS, rates of pediatric intensive care unit
      transfer, or seven-day readmission rates. By multiple regression analysis, the
      use of the O2 protocol was associated with a nearly 20% significant decrease in
      the length of hospitalization (p = 0.030). Conclusion: Use of O2 supplementation
      protocol increased LOS in the more ill patients with bronchiolitis but decreased
      overall LOS by having a profound effect on patients with mild bronchiolitis.

PMID- 29181039
TI  - Epidemiology and Genetic Diversity of Colistin Nonsusceptible Nosocomial
      Acinetobacter baumannii Strains from Russia for 2013-2014.
AB  - A high level of resistance to carbapenems in Acinetobacter baumannii strains
      severely limits therapeutic possibilities. Colistin is the last resort drug
      against such strains, although the cases of resistance to this drug have become
      more frequent. This article presents the epidemiological features and genetic
      diversity of colistin nonsusceptible A. baumannii strains collected as part of a
      national multicenter epidemiological study of the antibiotic resistance of
      pathogens of nosocomial infections (MARATHON), which was conducted in 2013-2014
      in Russia. A total of 527 A. baumannii isolates were collected, 10 (1.9%) of
      which were nonsusceptible to colistin. The majority of nonsusceptible A.
      baumannii isolates to colistin showed resistance to carbapenems and had the genes
      of the acquired OXA-40-like carbapenemases (n = 6). In one case, a combination of
      OXA-23-like + OXA-40-like (n = 1) genes was identified. One strain had the
      multidrug-resistant (MDR) phenotype, 6 isolates had extensively drug-resistant
      (XDR) phenotype, and 3 isolates had pandrug-resistant (PDR) phenotype. Among the
      colistin nonsusceptible A. baumannii isolates, 6 individual genotypes were
      identified, most of which belonged to successful international clones
      (CC92OXF/CC2PAS, n = 4; CC944OXF/ST78PAS, n = 4; CC109OXF/CC1PAS, n = 1).

PMID- 29181040
TI  - Is there a determining factor that predicts mortality in patients with congenital
      diaphragmatic hernia?
AB  - Aim: This study was designed to investigate the factors affecting the prognosis
      in neonates with congenital diaphragmatic hernia (CDH) who were treated in our
      clinic. These factors included prenatal lung-head ratio (LHR), prenatal stomach
      and liver presence in the thorax, blood gases in the first 24 h and the modified
      ventilation index (MVI). Material and methods: The study was carried out
      retrospectively in 30 neonates with prenatally diagnosed left CDH who were
      treated in our clinic between January 2007 and 2013. Data were collected,
      evaluated, and statistically analyzed for gender, birth weight, gestational age,
      prenatal LHR, prenatal presence of stomach and liver in the thorax, postnatal
      initial blood gases in the first 24 h and MVI. Results: The median LHR for non
      survivors was 1.49 and for survivors 1.51. No statistically significant
      difference in LHR was detected between survivors and non-survivors. In 19
      neonates, prenatal ultrasonography (USG) revealed intrathoracic stomach, and 9 of
      these infants died. Intrathoracic liver was seen in 15 neonates, and 9 of these
      died. A statistically significant difference was not found between survivors and
      non-survivors in the intrathoracic liver or intrathoracic stomach neonates. A
      comparison between the non-survivors and survivors showed a median pH value of
      7.10 in non-survivors and 7.24 in survivors (p = 0.002). The median PaCO2 value
      was 69.4 mm Hg in non-survivors and 51.9 mm Hg in survivors (p = 0.01). There
      were statistically significant differences in pH and PaCO2 values. The median
      value of MVI was 33 in survivors and 100 in non-survivors. There was a
      statistically significant difference between overall non-survivors and survivors
      in the MVI value (p < 0.05). Conclusions: Based on the findings, postnatal pH,
      and PaCO2 and MVI values are favorable prognostic factors in CDH in our selected
      group of patients.

PMID- 29181041
TI  - Video-assisted thoracic surgery in hemothorax evacuation after cardiac surgery or
      cardiac interventions.
AB  - Introduction: Cardiac surgery and cardiac interventions are associated with the
      risk of iatrogenic complications, including hemothorax. Minimally invasive
      methods of evacuating hemothorax include video-assisted thoracic surgery (VATS).
      Aim: This paper presents this method and provides its detailed analysis. Material
      and methods: The VATS procedures were used to evacuate hemothorax in 8 patients
      (7 after cardiac surgery and 1 after a cardiac intervention). Complete three-port
      VATS was performed in 7 patients, while 1 patient underwent assisted VATS due to
      a large number of adhesions. Results: On average, the repeat procedures were
      performed on the 20th postoperative day (10th-58th postoperative day). In 6 (75%)
      cases the VATS intervention was the third surgical intervention performed. One
      patient, operated on 12 days after the original procedure, was diagnosed with
      active arterial bleeding, which required conversion to a classic procedure using
      median sternotomy. No postoperative wound infection was noted. Complete
      hemothorax removal was achieved in all patients. Conclusions: Classic median
      sternotomy is the standard approach for hemothorax evacuation. However, it may
      sometimes be burdened with a high perioperative risk due to massive mediastinal
      adhesions in the late postoperative period. Additionally, access through the
      postoperative wound appears to be associated with a higher risk of local
      infection and sternal instability. Hemodynamically stable patients in the late
      postoperative period, with stable sternums and healed postoperative wounds, are
      good candidates for VATS aiming to evacuate hemothorax. The VATS is an effective
      procedure for evacuating hemothorax.

PMID- 29181042
TI  - Associations between coronary artery disease, aneurysm and ectasia.
AB  - Aim: Investigation the frequency and contribution of coronary artery
      aneurysm/ectasia in addition to their correlation with coronary artery disease
      (CAD). Material and methods: We retrospectively evaluated the coronary
      angiography records of 6500 adult consecutive patients, and 418 of them were met
      inclusion criteria and used in the present study. The CAD was defined as the
      presence of angiographic coronary stenosis of > 50% of the luminal diameter in no
      less than one of the epicardial coronary arteries. Moreover, the prevalence and
      features of the coronary artery aneurysm/ectasia among the cases with and without
      CAD were compared. Results: We observed coronary artery aneurysm (CAA) and
      ectasia (CAE) in 6.6% of the patients with significant CAD (+), and 6.1% of the
      patients with significant CAD (-) (p = 0.2). The percentage of coronary artery
      aneurysms was significantly higher in CAD (+) patients than in CAD (-) patients
      (0.8% vs. 0.4%, p = 0.015). The percentage of coronary artery ectasia showed no
      variation between CAD (+) patients and CAD (-) patients (5.8% vs. 5.7%, p =
      0.47). The frequency of spotting aneurysm on a single coronary artery was higher
      than discerning aneurysm on two or three coronary arteries. Conclusions: Presence
      of CAA or CAE cases is often encountered in those who have undergone angiography
      procedures. Furthermore, CAA and CAE should not be considered as simple dilations
      of vessels. Further studies are needed to determine the effective procedures for
      the treatment and prognostic evaluations of the patients with CAA or CAE.

PMID- 29181043
TI  - Results of open heart surgery in Jehovah's Witness patients. Single centre
      experience.
AB  - Aim: Evaluation the results in patients from the religious community of Jehovah's
      Witness (JW) undergoing open heart surgery at our institution. Material and
      methods: Between September 2011 and March 2015, 21 patients with a religious
      background of the JW church underwent open heart surgery at our institution
      performed by the same surgical team. Mean age was 68.43 +/-8.93 years. There were
      13 (61.9%) female patients. Recombinant human erythropoietin was administered to
      every patient with a hemoglobin value < 12.0 g/dl. Nine patients undergoing
      isolated coronary artery revascularization were operated on without
      cardiopulmonary bypass. Seven patients underwent combined surgery and 5 patients
      underwent aortic valve replacement via ministernotomy. The mean follow-up time
      was 16.45 +/-11.09 months (range: 1.67-44.3 months). Results: Mean baseline
      hematocrit serum level was 40.15 +/-3.34% (range: 34.5-46.1%). Perioperatively
      the hematocrit serum levels decreased to the mean level of 29.89 +/-4.31% (range:
      21.4-36.3%). The mean hematocrit value at discharge was 30.85 +/-3.59% (range:
      23.5-38.4%). One death was observed in the perioperative period. Five (24%)
      patients suffered from sternum wound infection requiring vacuum-assisted therapy.
      During the follow-up period 1 patient died due to a non-cardiac related cause.
      Conclusions: After careful preoperative preparation the results of open heart
      surgery in JW were very good, including combined procedures. The decrease of
      hematocrit serum levels significantly characterizing the postoperative period was
      highly acceptable in this series. Nevertheless, the number of sternum wound
      infections was a limiting factor for prompt postoperative recovery.

PMID- 29181044
TI  - Clinical features, management and mortality in diabetic and non-diabetic patients
      with heart failure - observations from the COMMIT-HF registry.
AB  - Introduction: Diabetes mellitus (DM) and heart failure (HF) are two common
      diseases that often co-exist. Aim: To explore clinical characteristics,
      management strategies and rates of 3-year mortality among diabetic and non
      diabetic patients hospitalised in a highly specialized interventional cardiology
      centre. Material and methods: We used data from COMMIT-HF (COnteMporary
      Modalities In Treatment of Heart Failure), which is a single-centre,
      observational, prospective registry of patients with symptomatic chronic systolic
      HF (LVEF < 35%). Data collected included demographics, clinical characteristics,
      medical history, inpatient therapies and procedures. Follow-up was based on the
      information acquired from the national health-care provider. Results: We analysed
      1397 patients out of the total of 1798 patients included in the COMMIT-HF
      registry between 2009 and 2013. We identified 595 (42.6%) diabetic and 802
      (57.4%) non-diabetic patients. Compared to patients without DM, patients with
      type 2 DM had a higher rate of comorbidity. Frequency of death in patients with
      DM during the 3-year follow-up was significantly higher than in patients without
      DM (199 (33.4%) vs. 163 (20.3%), p < 0.0001, respectively). Conclusions: In the
      analysed HF population representing patients receiving typical, everyday clinical
      care, the prevalence of DM is 42.6%. Diabetes mellitus has deleterious effects on
      renal function and symptoms as assessed by the New York Heart Association
      functional class. DM remains associated with increased frequency of death in
      patients with HF, in spite of recent pharmacological and device-based advances in
      HF management.

PMID- 29181045
TI  - Late subclinical hemolysis and long-term outcomes after aortic valve replacement
      with On-X mechanical prostheses - a preliminary single-center report.
AB  - Introduction: Aortic valve replacement (AVR) with a mechanical prosthesis is not
      free from late complications. Aim: To evaluate the prevalence of subclinical
      hemolysis after AVR with On-X prostheses and assess its impact on long-term
      outcomes. Material and methods: The prospective study included 84 consecutive
      patients aged 58.3 +/-10.3 years who underwent AVR. They were retrospectively
      split into group H (n = 12; 14.3%) with prosthesis-related subclinical hemolysis
      and a control group (C; n = 72; 85.7%). All operations were performed via median
      sternotomy using cardio-pulmonary bypass. At the end of follow-up,
      echocardiography was carried out and blood samples for morphology and
      biochemistry (lactate dehydrogenase (LDH), bilirubin, haptoglobin) were taken.
      Results: The rate of subclinical hemolysis in patients with properly working
      prostheses was 14.3% and it was the highest (33.3%) for the smallest valves.
      Although an improvement in functional status was noted in both groups, it was
      less evident in group H than in group C (p = 0.007). At the end of follow-up,
      97.2% in group C and 75.0% in group H were found in NYHA classes I and II.
      Patients in group H had significantly lower hemoglobin, hematocrit, and
      haptoglobin and higher LDH activity than group C subjects. In group H, systolic
      gradients of On-X valves were higher whereas effective orifice area was smaller
      than in group C. Conclusions: Our study proved that prosthesis-induced
      subclinical hemolysis is seen even after implantation of the latest generation
      mechanical prostheses, particularly of small diameter, and its degree may impact
      late outcome.

PMID- 29181046
TI  - Role of dual source multidetector row cardiac computed tomography angiography in
      diagnosis and management of congenital heart disease patients.
AB  - Introduction: Primary evaluation of patients with congenital heart disease (CHD)
      traditionally relies on echocardiography and conventional cardiac angiography
      (CCA), both of which have potential limitations. Aim: To test the hypothesis that
      cardiac computed tomography angiography (CCTA) is useful in the diagnosis and
      management of these patients. Material and methods: The 3-year observational,
      analytical, retrospective, cohort study included a total of 111 tomographic
      studies of patients with congenital heart disease. Computed tomography scans were
      read twice and medical records were reviewed. The Aristotle complexity was
      assessed as well as and the contribution of new data in relation to clinical
      suspicion and diagnostic change was evaluated by two expert readers who were
      blinded for clinical outcome in consensus reading. The confidence interval was
      set at 95% and a p-value of < 0.05 was used as the cutoff for statistical
      significance. Results: In total, 111 patients were included (56 men and 55 women)
      with a mean age of 7.2 years (1 day-71 years). The therapeutic procedure was
      performed without additional tests in 85.8% of patients. New findings were
      observed in 60.4% of patients and a subsequent change in management in 46.9%. New
      unexpected findings in CCTA prompted changes in management in 86.8% of patients.
      There were no significant differences in age between patients with new findings
      vs. patients without such findings in CCTA suggesting that CCTA-supported
      diagnosis of CHD is independent of age. Conclusions: Use of dual-source cardiac
      computed tomography yields good diagnostic performance in congenital heart
      disease, prompts changes in management in more than one-third of patients, and
      reveals new findings in relation to the presumed diagnosis in most patients.

PMID- 29181048
TI  - Interpreting myocardial perfusion scintigraphy using single-photon emission
      computed tomography. Part 1.
AB  - This article discusses the protocol for myocardial perfusion scintigraphy
      performed with single-photon emission computed tomography (SPECT). Indications
      for SPECT are listed with consideration given to the results of the increasingly
      more common angio-CT examinations of the coronary arteries (multislice computed
      tomography). The paper also presents basic information about interpreting the
      results, including the scores of left ventricle myocardial perfusion using the 17
      segment polar map, and explains the concept of total perfusion deficit.

PMID- 29181047
TI  - Approaching the 50th anniversary of the first Fontan procedure. What is the
      current state of treatment provided to patients with functional single
      ventricles?
AB  - Nearly 50 years after the pioneering procedure performed by Francis Fontan and
      Eugene Baudet, which has saved the lives of thousands of children, there are
      still more questions than answers regarding therapeutic management. The complex
      pathophysiology of Fontan circulation, the lack of clear guidelines, and the
      shift in the care of such patients from pediatric cardiological and cardiac
      surgical centers to ones dealing with adult patients, cause new threats. This
      paper outlines the fundamental issues related to the pathophysiology of Fontan
      circulation and reviews the literature on the methods of treating complications
      characteristic of this group of patients.

PMID- 29181049
TI  - Paravalvular leak of a mechanical mitral valve prosthesis associated with
      Burkholderia cepacia subacute endocarditis: a rare case successfully treated by
      multidisciplinary approach.

PMID- 29181050
TI  - Acute pulmonary hemorrhage after dislocation of transcatheter aortic valve
      prosthesis.

PMID- 29181051
TI  - False-positive lung positron emission tomography-computed tomography result in a
      patient with a history of cancer.

PMID- 29181052
TI  - Pulmonary epithelioid hemangioendothelioma imitating lung cancer.

PMID- 29181053
TI  - Progression of coronary artery disease in a HIV-infected patient previously
      treated for ascending aorta aneurysm.

PMID- 29181054
TI  - Predictive values of Notch signalling in renal carcinoma.
AB  - Introduction: Notch signalling, an evolutionarily conserved mechanism of cellular
      differentiation and tissue remodelling, is frequently deregulated in several
      human malignancies, including renal cell carcinoma (RCC). However, the prognostic
      value of individual Notch pathway members in RC subtypes remains indefinable. The
      present study investigates whether the differential expression of Notch members
      has a contrary effect on disease-free survival (DFS) in clear cell renal cell
      carcinoma (KIRC), papillary cell renal cell carcinoma (KIRP) and chromophobe
      renal cell carcinoma (KICH) patients. Material and methods: The predictive value
      of 19 Notch members was evaluated in KICH, KIRC and KIRP patient cohorts from The
      Cancer Genome Atlas (TCGA). Results in the form of Kaplan-Meier survival plots
      with the p-value calculated (log-rank test, p < 0.05) enabled the patients to be
      split into favourable/unfavourable prognosis groups regarding expression of Notch
      members. Results: More specifically, lowered expression of ADAM17 correlated with
      good prognosis in KICH, KIRC and KIRP (HR = 7.79, p = 0.03; HR = 3.98, p = 0.051;
      HR = 11.24, p < 0.001, respectively). Additionally, HES4 differentiated KICH and
      KIRC, as its higher expression correlated with good prognosis in KICH and
      favourable lowered expression in KIRC (HR = 0.11, p = 0.015; HR = 2.42, p <
      0.001, respectively). Conclusions: Our analysis could be valuable for better
      understanding of the molecular mechanism of renal carcinoma. The expression of
      Notch pathway members could be a useful biomarker for predicting
      favourable/unfavourable prognosis in patients with RCC.

PMID- 29181055
TI  - Functions of the AP-2alpha gene in activating apoptosis and inhibiting
      proliferation of gastric cancer cells both in vitro and in vivo.
AB  - Introduction: This study was designed to investigate the potential function of
      the activating protein 2alpha (AP-2alpha) gene in controlling the proliferation
      and apoptosis of gastric cancer. Material and methods: Gastric cancer cell line
      MCG-803 cells and normal cell line GES-1 cells were selected to transfect
      pcDNA3.1(+)-AP-2alpha and pcDNA3.1(+) plasmids, respectively. Both mRNA and
      protein levels of AP-2alpha in each group transfected with the pcDNA3.1(+)-AP
      2alpha plasmids were up-regulated after 48 h by real-time PCR and Western
      blotting analysis, leading to marked proliferation inhibition and significant
      cell cycle arrest. Results: pcDNA3.1(+)-AP-2alpha reduced tumor tissue growth in
      a subcutaneous tumor gastric carcinoma nude mouse model. Protein over-expression
      of AP-2alpha in the nude mouse model was accompanied by down-regulation of Blc-2
      and ErbB2, resulting in the up-regulation of caspase-3, -8, and -9, ERalpha and
      p21WAF1/CIP1. Conclusions: The reintroduction of the AP-2alpha gene by pcDNA3.1
      could inhibit gastric tumor growth in vitro and in vivo, which may be an
      alternative future therapeutic molecular target for human gastric cancer.

PMID- 29181056
TI  - Prognostic implications of phosphatidylinositol 3-kinase/AKT signaling pathway
      activation in gastric carcinomas.
AB  - Introduction: Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway
      plays a critical role in carcinogenesis and resistance to anticancer drugs. In
      this study, gastric carcinomas (GC) were investigated and statistical analyses
      were performed concerning the correlation between the clinicopathological
      features and activation of the PI3K/AKT pathway. Material and methods:
      Immunohistochemistry for p-AKT, p-mTOR and PTEN was performed in 239 GC and 200
      non-neoplastic gastric tissues. The clinicopathological parameters were recorded
      from the medical charts. Statistical significance was defined by a p-value <
      0.05. Results: High p-AKT expression was observed in 10% of the normal gastric
      tissue and in 90% of GC, and it was significantly associated with tumor size (p <
      0.001), T3/T4 tumors (p < 0.001), and presence of metastases (p = 0.02).
      Similarly, p-mTOR positivity was found in GC cells, but not in the normal gastric
      mucosa, and was correlated with perineural invasion (p = 0.02) and T3/T4 tumors
      (p = 0.03). On the other hand, PTEN expression was weak and focal in the tumor
      cells, while in the normal gastric tissue this staining was strong and diffuse.
      Importantly, the expression of p-mTOR and PTEN was associated with overall
      survival. Conclusions: The results of the present study, characterized by the
      loss of PTEN expression and higher expression of p-AKT and p-mTOR in the majority
      of tumor cells, apparently are implicated in the carcinogenesis and progression
      of GC. The identification of p-mTOR and PTEN expression as prognostic factors
      corroborates the identification and use of potential target drugs that could be
      more efficient for the treatment of these patients.

PMID- 29181057
TI  - Tissue expression of beta-catenin and E- and N-cadherins in chronic hepatitis C
      and hepatocellular carcinoma.
AB  - Introduction: The role of Wnt/ beta -catenin signaling pathway in HCV-associated
      hepatocellular carcinogenesis is still unknown. Material and methods: This study
      aimed to perform quantitative analysis of immuno- and hybridocytochemical
      expression of beta -catenin, E- and N-cadherins and HCV proteins (C, NS3, NS5A)
      in long-lasting (>= 20 years) chronic hepatitis C (CH-C) (n = 54), hepatocellular
      carcinoma (HCC) (n = 61), and control liver samples (n = 8). Results: Typical
      membranous expression of beta -catenin in the control liver was higher than in
      the CH-C and HCC (p = 0.06). The mean beta -catenin tissue expression in CH-C was
      similar to controls, and significantly higher than that of HCC (p = 0.005). E
      cadherin expression was lower in CH-C than in the control (p = 0.045) and HCC (p
      < 0.001). In HCC both beta -catenin and E-cadherin expressions were significantly
      lower in comparison to controls (p = 0.02, p = 0.001, respectively). Positive
      correlations were found between beta -catenin and E-cadherin (in CH-C and HCC),
      beta -catenin and N-cadherin (HCC), E- and N-cadherins expressions (HCC) (p <
      0.05 in all cases). In CH-C the positive correlation was demonstrated between
      NS5A protein and beta -catenin, and between the all HCV proteins (C, NS3, NS5A)
      and E-cadherin expression (p < 0.05 in all cases). Conclusions: Alterations in
      cellular locations of beta -catenin and E-cadherin in CH-C and HCC pointed to
      structural disturbances in intercellular junctions in the livers and presence of
      the transcriptionally inactive form of beta -catenin. The reduced expression of E
      cadherin in long-lasting CH-C may represent an early indicator of the epithelial
      mesenchymal transition. The most important role in modulation of the Wnt/ beta 
      catenin pathway in vivo is probably played by the NS5A viral protein.

PMID- 29181058
TI  - Value of CNRIP1 promoter methylation in colorectal cancer screening and prognosis
      assessment and its influence on the activity of cancer cells.
AB  - Introduction: The aim of the study was to investigate the effect of CNRIP1
      promoter methylation on the proliferative, invasive and migration potential of
      colorectal cancer cells, including its potential use for the early detection and
      prognostic assessment of colorectal cancer. Material and methods: Quantitative
      methylation-specific PCR (qMSP) was used to detect the methylation status of the
      CNRIP1 promoter region in peripheral blood samples drawn from patients with
      colorectal adenocarcinoma, benign colorectal adenoma, and matched healthy
      controls. Putative CpG methylation sites were then pyrosequenced. We subsequently
      suppressed CNRIP1 methylation within colon cancer cells via treatment with 5
      azacytidine and overexpressed colon cancer cells by transfection with a CNRIP1
      overexpression pcDNA3.0 plasmid. Thereafter, the CNRIP1 methylation status and
      mRNA and protein expressions levels were determined. Finally, the proliferative,
      invasive and migration abilities of cell lines were determined with the CCK-8 and
      Transwell cell assays. Results: There were differences in the methylation status
      at loci 2216, 2226, 2231, 2245, and 2254 within the promoter region of CNRIP1
      between patients with colorectal adenocarcinoma, colorectal adenoma, and healthy
      volunteers. The methylation status of CpG sequence 2245 significantly correlated
      with tumor diameter, invasion depth, TNM stage, grade, and lymph node metastasis
      (p < 0.05). The proliferative, invasive and migration abilities of colon cancer
      cells treated with 5-azaC or transfected with a CNRIP1-overexpression plasmid
      were significantly impaired relative to negative controls (p < 0.05).
      Conclusions: The methylation status at locus 2245 within the CNRIP1 promoter
      region has potential value for the early detection and prognostic evaluation of
      colorectal cancers. Demethylation of the CNRIP1 promoter or overexpression of
      CNRIP1 can reduce the proliferative and migration abilities of colon cancer
      cells.

PMID- 29181059
TI  - Polymorphism of MSH2 Gly322Asp and MLH1 -93G>A in non-familial colon cancer - a
      case-controlled study.
AB  - Introduction: Our aim was to determine the effect of the single nucleotide
      polymorphisms (SNP) -93G>A of the MLH1 gene (rs1800734) and Gly322Asp of the MSH2
      gene (rs4987188) on the risk of colon cancer (CC) and identify any relationship
      with clinical factors. Material and methods: The study included 144 unrelated
      patients with sporadic CC (71 males; mean age: 61.7 +/-11 years) and 151 control
      patients (74 males; mean age: 63 +/-11 years). DNA was extracted from peripheral
      blood lymphocytes, and genotypes were determined by polymerase chain reaction
      restriction fragment length polymorphism. Results: In our population, the
      homozygous G/G genotype of the -93G>AMLH1 gene increased the risk of sporadic CC
      (OR = 2.07; 95% CI: 1.11-3.83; p < 0.02). For A/G and A/A genotypes, the MLH1
      93G>A polymorphism was significantly more common in women (p = 0.034). The SNP
      demonstrated differences in allele distribution according to the location of the
      tumor, i.e. right vs. left side (p = 0.014), and disease recurrence (p = 0.022).
      Significant differences were found in the occurrence of Gly322Asp of MSH2 with
      regard to primary and recurrent disease (p = 0.001). Conclusions: The -93G>AMLH1
      polymorphism plays an important role in evaluating the risk of sporadic CC. It
      can also be used as an indicator in some patients with left-sided and recurrent
      tumors. MSH2 Gly322Asp is a potential marker in patients with risk of recurrence.

PMID- 29181060
TI  - Expression of multidrug resistance protein P-glycoprotein in correlation with
      markers of hypoxia (HIF-1alpha, EPO, EPO-R) in invasive breast cancer with
      metastasis to lymph nodes.
AB  - Introduction: Overexpression of the mdr-1 gene is the earliest discovered
      mechanism of multidrug resistance, which is associated with P-glycoprotein (P-gp)
      - a cell membrane protein responsible for the efflux of drugs of various
      structures out of cancer cells. Although the expression of P-glycoprotein has
      been demonstrated in many cancer types, its relation to markers of hypoxia such
      as HIF-1alpha, EPO-R or EPO in invasive breast cancer is not well established.
      The aim of this research was to analyze the co-expression of P-glycoprotein and
      the markers of tissue hypoxia HIF-1alpha, EPO, and EPO-R by immunohistochemistry
      in invasive breast cancer classified according to the presence of steroid
      receptors and the HER2 receptors. Material and methods: Tissue samples were
      collected from 58 patients with the diagnosis of invasive breast cancer with
      lymph node metastases. The expression of P-gp, HIF-1alpha, EPO-R and EPO was
      determined by immunohistochemistry. Results: Of all the invasive breast cancers
      with lymph node metastases, 15.5% expressed P-gp in cell membrane and tumor blood
      vessels. In our research, there was a significant positive correlation between
      HER2-positive tumors that did not express steroid receptors (ER-/PR-/HER2+), and
      P-gp expression (p = 0.049, r = 0.105). Moreover, there was a significant
      positive correlation between EPO expression and P-gp (p < 0.001, r = 0.474), and
      between HIF-1alpha expression and P-gp (p = 0.00475, r = 0.371). Conclusions: We
      found that HIF-1alpha and EPO expression is significantly associated with P-gp
      expression in invasive breast cancer with lymph node metastases. An important
      result of our study is the demonstration of a correlation between P-gp expression
      and patients with HER2-positive breast tumors that do not express steroid
      receptors.

PMID- 29181061
TI  - Up-regulation of the long non-coding RNA RMRP contributes to glioma progression
      and promotes glioma cell proliferation and invasion.
AB  - Introduction: Gliomas are the most common malignant tumors of the brain. Long non
      coding RNAs (lncRNAs) play key regulatory roles in various tumors. In this study,
      we aimed to determine the expression and biological roles of lncRNA RMRP in
      glioma. Material and methods: The relative expression level of lncRNA RMRP was
      determined by quantitative real-time polymerase chain reaction (qRT-PCR) in a
      total of 39 patients with glioma. RNA interference (RNAi) approaches were used to
      investigate the biological functions of RMRP. The effect of lncRNA RMRP on
      proliferation was determined by CCK8 assay. Cell cycle and apoptosis were
      evaluated by flow cytometry analysis. Cell migration was explored by the wound
      healing assay. Cell invasion was investigated by the Transwell invasion assay.
      Results: LncRNA RMRP was up-regulated in human glioma tissues compared with
      normal brain tissues (p < 0.05). LncRNA RMRP up-regulation was significantly
      correlated with advanced tumor grade and low Karnofsky Performance Score (KPS) (p
      < 0.05). Moreover, patients with a high expression level of lncRNA RMRP had a
      relatively poor prognosis (p < 0.05). Multivariate analyses revealed that lncRNA
      RMRP expression served as an independent predictor for overall survival of glioma
      patients (p < 0.05). In addition, inhibition of lncRNA RMRP by RNAi significantly
      suppressed the proliferation, migration and invasion of glioma cells in vitro (p
      < 0.05). Conclusions: lncRNA RMRP might act as an oncogene and could be used as a
      therapeutic target for the treatment of glioma. Our findings provide an in-depth
      insight into the role of lncRNA RMRP in glioma progression.

PMID- 29181062
TI  - Investigation of platinum nanoparticle properties against U87 glioblastoma
      multiforme.
AB  - Introduction: Gliomas are the most aggressive and common primary tumors of the
      central nervous system (CNS). Many side effects of drugs containing platinum and
      their poor penetration of the CNS are major drawbacks in glioma therapy. The aim
      of the study was to investigate and compare the toxicity of platinum
      nanoparticles and cisplatin and their anticancer properties in examination with a
      U87 glioma cell line and tumor. Material and methods: Nanoparticles of platinum
      (NP-Pt) and cisplatin were incubated with U87 glioma cells or injected directly
      into tumor tissue. The biological properties of NP-Pt and cisplatin were compared
      through the morphology, viability, mortality, genotoxicity and the type of cell
      death of U87 glioma cells, the morphology and ultrastructure of glioma tumor, and
      expression of caspase-3, p53 and PCNA mRNA. Results: NP-Pt at concentrations of
      0.14 uM/ml, 0.29 uM/ml and 0.65 uM/ml had a harmful influence on viability of U87
      glioblastoma multiforme (GBM) cells, but also showed genotoxic properties as well
      as a pro-apoptotic effect on cancer cells. It was found that NP-Pt decreased the
      weight and volume of U87 GBM tumor tissue and caused pathomorphological changes
      in the ultrastructure and morphology of tumor tissue, but they also upregulated
      p53 and caspase-3 mRNA expression. Conclusions: The comparison between the
      effectiveness of glioblastoma treatment by NP-Pt vs cisplatin showed promising
      results for future studies. The results indicate that the properties of NP-Pt
      might be utilized for brain cancer therapy.

PMID- 29181063
TI  - Impact of connexin 43 coupling on survival and migration of multiple myeloma
      cells.
AB  - Introduction: Gap junctions (GJs) represent the best known intercellular
      communication (IC) system and are membrane-spanning channels that facilitate
      intercellular communication by allowing small signaling molecules to pass from
      cell to cell. In this study, we constructed an amino terminus of human Cx43
      (Cx43NT-GFP), verified the overexpression of Cx43-NT in HUVEC cells and explored
      the impact of gap junctions (GJs) on multiple myeloma (MM). Material and methods:
      The levels of phosphorylated Cx43(s368) and the change of MAPK pathway associated
      molecules (ERK1/2, JNK, p38, NFkappaB) were also investigated in our cell models.
      Cx43 mRNA and proteins were detected in both MM cell lines and mesenchymal stem
      cells (MSCs). Dye transfer assays demonstrated that gap junction intercellular
      communication (GJIC) occurring via Cx43 situated between MM and MSCs or MM and
      HUVECCx43NT is functional. Results: Our results present evidence for a channel
      dependent modulator action of connexin 43 on the migratory activity of MM cells
      toward MSCs or HUVECCx43-N was higher than those of spontaneous migration (p <
      0.05) and protection them from apoptosis in the presence of dexamethasone via
      cytokines secretion. In the meantime, the migration of MM cells involves an
      augmented response of p38 and JNK signaling pathway of carboxyl tail of the
      protein. Conclusions: Our data suggest that GJIC between MM and MSCs is one of
      the essential factors in tumor cell proliferation and drug sensitivity, and is
      implicated in MM pathogenesis.

PMID- 29181064
TI  - Diagnostic investigations of PLA2G16 and CDH11 expression levels as independent
      prognostic markers of human osteosarcoma.
AB  - Introduction: The aim of this study was to facilitate and deepen the
      understanding of the associations of the clinical significance of PLA2G16 and
      CDH11 in patients with osteosarcoma. Material and methods: We collected 50 paired
      osteosarcoma tissues and adjacent normal bone tissues and evaluated the
      expression of PLA2G16 and CDH11 by quantitavise reverse transcriptase real-time
      polymerase chain reaction. Results: PLA2G16 expression was upregulated in
      osteosarcoma tissues when compared with adjacent normal bone tissues, and the
      difference was statistically significant (4.78 +/-0.70 vs. 1.31 +/-0.65; p <
      0.05). Our data indicated that high expression of PLA2G16 was significantly
      related to advanced TNM stage and metastasis or recurrence (p < 0.05). The
      expression level of CDH11 was lower in osteosarcoma tissues (median relative
      expression level +/- SD: 6.29 +/-1.43) than adjacent normal bone tissues (mean +/
      SD: 13.72 +/-3.08, p < 0.05). Our findings demonstrated that decreased
      expression of CDH11 was strongly linked to advanced TNM stage, and metastasis or
      recurrence (p < 0.05). Log-rank analysis showed that patients with high
      expression of PLA2G16 have shorter overall survival than those with low
      expression. Moreover, shorter overall survival was significantly correlated with
      decreased expression of CDH11. Multivariate Cox proportional hazards analysis
      showed that PLA2G16 (p = 0.028; HR = 2.621; 95% CI) and CDH11 (p = 0.023; HR =
      2.81; 95% CI) expression and also metastasis or recurrence (p = 0.03; HR = 2.531;
      95% CI) were independent prognostic factors for poor overall survival of
      osteosarcoma patients. Conclusions: These findings suggest that PLA2G16 and CDH11
      expression can be independent prognostic factors for poor overall survival of
      patients with osteosarcoma.

PMID- 29181065
TI  - Down-regulation of microRNA-182 and microRNA-183 predicts progression of
      osteosarcoma.
AB  - Introduction: The aim of this study was to investigate the expression levels of
      microRNA-182 and microRNA-183 and their association with clinicopathological
      features in patients with osteosarcoma. Material and methods: Total RNA was
      purified from samples and noncancerous bone tissues and then quantitative real
      time polymerase chain reaction was applied to evaluate the expression levels of
      microRNAs, and their relationship with clinicopathological features and survival
      in osteosarcoma patients. Results: Our findings showed that expression of MiR-182
      was clearly lower in osteosarcoma bone tissue (mean +/- SD: 2.84 +/-.07) compared
      with noncancerous bone tissues (6.23 +/-1.72, p = 0.004). On the other hand,
      lower expression of MiR-183 was seen in osteosarcoma bone tissue (1.43 +/-0.59)
      when compared with normal tissues (4.36 +/-2.47, p = 0.036). Decreased expression
      of MiR-182 was clearly correlated with advanced clinical stage (p = 0.001),
      metastasis or recurrence (p = 0.024), and large tumor size (p = 0.032). Decreased
      expression of MiR-183 was associated with advanced TNM stage (p = 0.004), and
      metastasis or recurrence (p = 0.002). A multivariate Cox proportional hazards
      model revealed that low expression of MiR-182 and MiR-183 (p = 0.02; p = 0.016),
      TNM stage (p = 0.04), and metastasis or recurrence (p = 0.03) were significantly
      associated with poor survival as independent prognostic factors. Conclusions:
      These findings suggest that MiR-182 and MiR-183 may be associated with
      progression and metastasis of osteosarcoma.

PMID- 29181066
TI  - Stem cell factor in the serum of patients with esophageal cancer in relation to
      its histological types.
AB  - Introduction: Hematopoietic growth factors (HGFs), such as stem cell factor
      (SCF), may stimulate proliferation and differentiation of hematopoietic
      progenitor cells. Stem cell factor is also able to affect the growth of malignant
      tumors, including esophageal cancer (EC). The prognosis of EC patients' survival
      is still unfavorable. Thus, novel biomarkers are necessary to improve the
      diagnosis and prognosis of EC patients. The aim of this study was to determine
      the serum SCF concentrations in EC patients in relation to its histological types
      and compare these levels with the classical tumor marker - carcinoembryonic
      antigen (CEA). Material and methods: The study included 56 EC patients and 65
      healthy controls. Serum SCF and CEA concentrations were measured using
      immunoenzyme assays. Moreover, diagnostic criteria of both proteins tested and
      the survival of EC patients were assessed. Results: The serum SCF concentrations
      were lower in EC patients compared to healthy controls, but the difference was
      not significant, whereas CEA levels were higher in EC patients than in healthy
      subjects. The serum SCF concentrations were significantly higher in patients with
      adenocarcinoma of the esophagus (AC) than in patients with esophageal squamous
      cell carcinoma (ESCC). Moreover, the diagnostic sensitivity of SCF (88%) was
      higher than for CEA (29%) and increased for combined analysis of SCF with CEA.
      Conclusions: Our findings suggest the potential role of serum SCF in the
      diagnosis of EC patients, especially in combination with the classical tumor
      marker. However, due to the non-specific nature of SCF, this issue requires
      further investigations performed on a larger population of EC patients.

PMID- 29181067
TI  - Preoperative immunonutrition regulates tumor infiltrative lymphocytes and
      increases tumor angiogenesis in gastric cancer patients.
AB  - Introduction: An increased number of tumor infiltrative lymphocytes (TILs) is
      considered a favorable prognostic factor in various cancers because it is a
      marker of antitumoral activity of the immune system. In this prospective, non
      randomized clinical trial, we evaluated the impact of preoperative
      immunonutrition on tumor infiltrative lymphocytes and neoangiogenesis in
      cancerous tissue in patients with locoregional and resectable gastric
      adenocarcinoma. Material and methods: Patients with locoregional and resectable
      gastric adenocarcinoma were divided non-randomly into two study groups. The first
      (control) group included patients who had standard nutrition, and the second
      group included those who had immunonutrition for 7 days before surgery. The
      biopsy samples taken endoscopically in the preoperative period, as well as the
      gastrectomy samples, were subjected to immunohistochemical staining for
      quantitative analysis of CD4, CD8, CD16, CD56, CD31 and CD105 antibodies. Main
      outcome measures were CD4-to-CD8 ratio and CD105 levels. Results: Fifty patients
      were included in the study between January 2013 and December 2014. Twenty-five
      patients were assigned to each of the first and second group. The CD4-to-CD8
      ratio and CD105 levels determined in endoscopic biopsy samples were similar in
      both groups. The CD4-to-CD8 ratio in gastrectomy samples was significantly higher
      in the first group (p = 0.0001). The CD105 levels in gastrectomy samples were
      significantly lower in the first group (p = 0.01). Conclusions: Seven-day
      preoperative immunonutrition use regulates TILs in gastric cancer patients, but
      prolonged use increases tumor angiogenesis.

PMID- 29181068
TI  - Immunohistochemical features and staging of early gastric cancer.
AB  - Introduction: The aim of this study was to analyze the particularities of early
      gastric cancer (EGC) and their importance for staging, prognosis, and therapy.
      Material and methods: A total of 338 GCs diagnosed and surgically removed in
      three medical institutes from Eastern Europe were retrospectively examined, and
      the EGCs were further examined. Besides the demographic factors and tumor
      characteristics, immunostains were performed with E-cadherin, HER-2, p53, Ki67,
      MLH-1, MSH-2, COX-2, VEGF-A, CD31, and CD105. Results: From the 338 GCs, 29 were
      EGCs, the average being similar in Poland and Hungary (12.37% and 13.33%
      respectively) but lower in Romania (5.61%). The rate of lymph node metastases was
      20.69% (n = 6). Two of the cases presented liver metastases, both of them having
      a multifocal aspect. In 1 of these cases, limited to the mucosa, intramural
      carcinomatosis of the lymph vessels was seen in submucosa, muscularis propria,
      and subserosa. COX-2 positivity was observed in 14 (48.72%) cases. COX-2 was
      directly correlated with microvessel density determined with CD31 (p < 0.001) and
      CD105 (p = 0.03). Same correlation with CD31 and CD105 was seen for HER-2 (p =
      0.03 and p = 0.0007). The only negative independent prognostic factors for
      overall survival were tumor localization at the proximal stomach and male gender,
      regardless of age. Conclusions: In EGCs, intramural carcinomatosis of the lymph
      vessels and multifocality should be separately described in every surgical
      pathology report, as indicators of aggressiveness. Microsatellite status, E
      cadherin, HER-2, p53, and Ki67 do not have prognostic value in EGC, but the
      highly angiogenic pattern is a possible therapeutic target.

PMID- 29181069
TI  - Sorafenib combined with hepatectomy in patients with intermediate-stage and
      advanced hepatocellular carcinoma.
AB  - Introduction: Guidelines based on the Barcelona Clinic Liver Cancer (BCLC)
      classification system recommend that hepatic resection should be performed only
      in patients in BCLC stage A. Patients with stage B or stage C should receive
      palliative or no treatment. However, actual clinical practice varies, and a
      recent analysis of hepatocellular carcinoma (HCC) surgery outcomes in high volume
      surgical centers throughout the world concluded that hepatectomy can provide
      survival benefit for selected patients in all three BCLC stages. The aim of this
      study is to evaluate the efficacy and tolerability of adjuvant sorafenib after
      hepatic resection in patients with intermediate-stage and advanced HCC. Material
      and methods: In a retrospective case-control study involving 81 patients with
      intermediate/advanced HCC, 27 who received sorafenib 400 mg BID (median duration
      7.33 months) following hepatic resection were compared with a matched group of 54
      patients who received hepatic resection only. Overall survival (OS) and time to
      recurrence (TTR) were evaluated over a median follow-up time of 14.5 months.
      Results: The median OS was significantly longer in the surgery+sorafenib group
      than in the surgery-only group (18.6 vs. 11.9 months, respectively; p = 0.014).
      However, the median TTR did not differ significantly between the 2 groups (p =
      0.291). Conclusions: Sorafenib is effective as adjuvant therapy after liver
      resection in intermediate-stage and advanced HCC, and can be considered a viable
      treatment option following surgery in such patients.

PMID- 29181070
TI  - Investigation of clinicopathological parameters in emergency colorectal cancer
      surgery: a study of 67 patients.
AB  - Introduction: The aim of the present study was to establish, having adjusted for
      case mix, the size of the differences in postoperative mortality and 5-year
      survival between patients presenting as an emergency with evidence of obstruction
      and perforation and the association of clinicopathological factors with mortality
      (bivariate analyses). Material and methods: The study included 67 patients who
      presented with colorectal cancer (CRC) between 2009 and 2013 in Iran. The mean
      age of the patients was 59.7 years. Of the 67 patients, 37 (55.22%) were male and
      30 (44.77%) were female. Certain parameters that correlated with CRC and surgical
      treatment were investigated. Results: Our results showed that 46 (68.65%)
      patients had obstruction, while perforation was observed in 21 (31.34%) cases.
      Among the patients with obstruction, obstruction of the right colon was observed
      in 29 (43.28%) cases. There was no significant difference in mortality rate
      between right and left colonic obstruction. Based on the bivariate analyses, our
      findings showed that death of patients was significantly related to tumor grade
      (p = 0.02) and TNM staging (p = 0.026), but no association was found between
      other parameters and death, including age, sex, and tumor site. Conclusions:
      Compared with patients who undergo elective surgery for colon cancer, those who
      present as an emergency with evidence of obstruction or perforation have higher
      postoperative mortality rates and poorer cancer-specific survival. Also,
      colorectal cancer patients with emergency surgery showed aggressive
      histopathology and an advanced stage.

PMID- 29181071
TI  - Application of artificial neural networks for predicting presence of non-sentinel
      lymph node metastases in breast cancer patients with positive sentinel lymph node
      biopsies.
AB  - Introduction: The aim of this study was to present a new predictive tool for non
      sentinel lymph node (nSLN) metastases. Material and methods: One thousand five
      hundred eighty-three patients with early-stage breast cancer were subjected to
      sentinel lymph node biopsy (SLNB) between 2004 and 2012. Metastatic SLNs were
      found in 348 patients - the retrospective group. Selective axillary lymph node
      dissection (ALND) was performed in 94% of cases. Involvement of the nSLNs was
      identified in 32.1% of patients following ALND. The correlation between nSLN
      involvement and selected epidemiological data, primary tumor features and details
      of the diagnostic and therapeutic management was examined in metastatic SLN
      group. Multivariate analysis was performed using an artificial neural network to
      create a new nomogram. The new test was validated using the overall study
      population consisting of the prospective group (365 patients - SLNB between 01
      07.2013). Results: Accuracy of the new test was calculated using area under the
      receiver operating characteristics curve (AUC). We obtained AUC coefficient equal
      to 0.87 (95% confidence interval: 0.81-0.92). Sensitivity amounted to 69%,
      specificity to 86%, accuracy - 80% (retrospective group) and 77%, 46%, 66%
      (validation group), respectively. The Memorial Sloan-Kettering Cancer Center
      (MSKCC) nomogram the calculated AUC value was 0.71, for Stanford - 0.68, for
      Tenon - 0.67. Conclusions: In the analyzed group only the MSKCC nomogram and the
      new model showed AUC values exceeding the expected level of 0.70. Our nomogram
      performs well in prospective validation on patient series. The overall assessment
      of clinical usefulness of this test will be possible after testing it on
      different patient populations.

PMID- 29181072
TI  - Retrospective evaluation of histopathological examinations in invasive ductal
      breast cancer of no special type: an analysis of 691 patients.
AB  - Introduction: Invasive ductal carcinoma (IDC) is the most common type of breast
      cancer in women and accounts for about 80% of all breast cancers. Material and
      methods: The material consisted of histological preparations derived from 691
      patients treated for IDC-NST. Results: In our own study material, invasive ductal
      breast cancer of no special type accounted for more than 60% of cases, with the
      largest percentage of tumors being classified as G2 (53.96%) and G3 (28.98%). In
      terms of tumor size, the most common IDC-NST tumors were those of stage T1c
      (34.59%) and T2 (35.31%). The incidence of lymph node involvement was also
      assessed to reveal that no lymph node metastases were present in 45.44% of IDC
      NST tumors. In the histopathological analysis of IDC-NST, significant statistical
      correlation was demonstrated between the presence of lymph node metastases and
      the histological malignancy grade (N0/G1-G3 p = 0.0103; N1A/G1-G3 p = 0.0498;
      N1B/G1-G3 p< 0.001; N3/G1-G3 p = 0.0027; N4/G1-G3 p < 0.001), between the
      presence of lymph node metastases and the tumor size (N0/T1-T4 p = 0.00295;
      N1B/T1-T4 p < 0.001; N2/T1-T4 p < 0.001; N2A/T1-T2 p < 0.001; N4/T1-T4 p < 0.001;
      Nx/T1-T4 p = 0.0447), as well as between the histological malignancy grade and
      the tumor size (G1/T1-T4 p < 0.001; G1/2/T1-T4 p < 0.001; G2/3/T1-T4 p < 0.0267).
      Conclusions: Own research demonstrated that the most common histological type of
      breast cancer is invasive ductal carcinoma of no special type (IDC-NST);
      statistically significant correlations were demonstrated in IDC-NST patients
      between the lymph node involvement status and the histological malignancy grade
      or tumor size as well as between the histological malignancy grade and the tumor
      size.

PMID- 29181073
TI  - One-step nucleic acid amplification analysis of sentinel lymph nodes in papillary
      thyroid cancer patients.
AB  - Introduction: It is essential to look for methods to define the need for central
      lymphadenectomy for papillary thyroid cancer patients. The aim is to determine
      the efficacy of one-step nucleic acid amplification (OSNA) and sentinel lymph
      node (SLN) biopsy in the intraoperative detection of nodal involvement. Material
      and methods: This prospective, experimental study enrolled 49 patients with
      clinically negative lymph nodes. Intraoperatively, 1% Patent Blue dye was
      injected intratumorally. Lymph nodes that stained blue were defined as SLNs. They
      were directly cut into blocks at 2-mm intervals. Nonadjacent blocks were
      subjected to either the OSNA assay or histological examination. Results: Sixty
      five SLNs were found in 43 (87.8%) patients. There were 20 (30.8%)
      histopathologically positive SLNs. According to the OSNA, 22 (33.8%) SLNs were
      positive. The OSNA results were different from histopathology in 8 (12.3%) SLNs.
      The OSNA gave a positive result in 5 (7.7%) SLNs, while they were not involved
      according to the histopathology. However, OSNA upstaged N status from N0 to N1
      only in 2 (3.1%) patients. Inverse results (histopathology +, OSNA-) were
      obtained in 3 (4.6%) SLNs. Positive and negative predictive values (PPV and NPV)
      for OSNA were 0.77 and 0.93, respectively. The concordance rate between
      examinations was 85.5%. Conclusions: In some patients with clinically negative
      lymph nodes, OSNA and SLN biopsy may prevent unnecessary central lymphadenectomy.
      On the other hand, the sentinel lymph node biopsy may reveal the presence of
      potentially involved sentinel lymph nodes outside the central compartment. These
      SLNs can also be assessed by means of OSNA.

PMID- 29181074
TI  - Hindgut neuroendocrine neoplasms - characteristics and prognosis.
AB  - Introduction: The aim of the study was to analyze the clinicopathologic
      characteristics and prognostic factors of hindgut-rectal neuroendocrine
      neoplasms. Material and methods: The study included 38 patients with rectal
      neuroendocrine tumors who were treated at the Department of Endocrinology,
      Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznan,
      Poland from February 2010 to December 2015. The clinicopathological data were
      retrospectively reviewed, extracted, analyzed, and patients were followed up to
      determine their survival status. Follow-up data were available for all 38
      patients. Uni- and multivariate Cox regression analyses were performed to
      determine the prognostic factors significantly associated with overall survival.
      Results: The tumors occurred mostly in the middle and lower rectum, and the most
      typical symptoms experienced by patients were hematochezia and diarrhea. The
      median distance between the tumors and the anal edges was 4.7 +/-1.3 cm, and the
      median diameter of the tumors was 0.9 +/-1.2 cm. The major pathological types
      were neuroendocrine neoplasm G1 in 31 patients, and neuroendocrine neoplasm G2 in
      7 patients. Tumor-node-metastasis (TNM) stages I, II, III and IV tumors accounted
      for 76.3% (29/38), 5.3% (2/38), 7.9% (3/38) and 10.5% (4/38) of patients,
      respectively. The main treatment method was transanal extended excision or
      endoscopic resection. The 1-, 3- and 5-year survival rates of the whole group of
      patients were 100%, 83.7%, and 75.3%, respectively. Conclusions: Univariate
      analysis showed that age (p = 0.022), tumor diameter (p < 0.001), histological
      type (p < 0.001), and TNM stage (p < 0.001) were all prognostic factors.

PMID- 29181076
TI  - Intensive rehabilitation as an independent determinant of better outcome in
      patients with lung tumors treated by thoracic surgery.
AB  - Introduction: The frequency of postoperative complications after thoracic surgery
      remains high. Rehabilitation may become a procedure characterized by a high cost
      effectiveness ratio. The aim of the study was to determine the independent
      importance of intensive rehabilitation in patients with lung tumors treated by
      thoracic surgery. Material and methods: The prospective observational study
      included two groups of patients: 187 patients treated according to the historical
      scheme including thoracic surgery without specific exercises improving cardio
      pulmonary capacity, and 215 patients treated in agreement with the innovative
      algorithm of perioperative intensive physiotherapy until discharge from hospital.
      The evaluated clinical endpoints comprised bronchoscopy for pulmonary toilet and
      all other possible postoperative complications. Results: The use of intensive
      physiotherapy significantly shortened the duration of hospitalization through
      reducing the frequencies of different postoperative complications. The specific
      clinical benefit was associated with a significantly lower rate of bronchoscopy
      performance for pulmonary toilet (16% vs. 5.6%, p = 0.0006). Multivariate
      regression analyses revealed intensive physiotherapy as a significant independent
      predictor for all postoperative complications (OR = 0.57; 95% CI: 0.323-0.988; p
      = 0.045) and need to perform bronchoscopy for pulmonary toilet (OR = 0.24; 95%
      CI: 0.11-0.51; p = 0.0002). Conclusions: The study showed the strong independent
      positive effect of intensive rehabilitation in patients with lung tumors treated
      by thoracic surgery.

PMID- 29181075
TI  - MGMT promoter methylation as a potential prognostic marker for acute leukemia.
AB  - Introduction: It has been proved that genetic and epigenetic changes play a
      significant role in the development and progression of acute leukemia. The aim of
      our study was to evaluate the frequency and prognostic implications of genetic
      and epigenetic alterations in p15, MGMT, DNMT3A and TP53 genes in acute
      leukemias. Material and methods: We included in the study 59 patients with acute
      leukemia. Evaluation of TP53 and DNMT3A mutations was performed using sequencing
      analysis and PCR-RFLP, respectively. Methylation status of MGMT and p15 genes was
      evaluated using MSP and COBRA, respectively. For assessment of global DNA
      methylation ELISA-based kit was used. Results: We found that overall survival was
      higher for ALL patients. MGMT promoter methylation was significantly associated
      with patients age at the time of diagnosis (p = 0.03). TP53 and DNMT3A mutations
      were observed only in AML patients (16.67% and 8.8%, respectively). Patients with
      acute leukemia and p15 promoter methylation had significantly more frequently
      mutated TP53 gene (p = 0.04) and AML patients with p15 promoter methylation had
      significantly more frequently detected global hypomethylation of DNA (p = 0.009).
      In the group of ALL patients we noted an opposite trend: only patients negative
      for p15 promoter methylation were characterized by global DNA hypomethylation.
      Conclusions: Our findings demonstrate that MGMT promoter methylation can have a
      considerable impact on the development of acute leukemia in older patients.
      DNMT3A and TP53 mutations may play a significant role in AML development.
      However, further studies conducted in a larger cohort of patients are needed to
      determine its clinical utility.

PMID- 29181077
TI  - Updated analysis of vitamin D receptor gene FokI polymorphism and prostate cancer
      susceptibility.
AB  - Introduction: Polymorphisms of the vitamin D receptor (VDR) gene have been
      investigated in various case-control studies to evaluate prostate cancer
      susceptibility; however, published data on the association between vitamin D
      receptor gene FokI polymorphism and prostate cancer risk are inconclusive.
      Material and methods: To assess the impact of vitamin D receptor gene FokI
      polymorphism, we performed a meta-analysis of eligible studies including 9,720
      patients and 9,710 control subjects. Results: The overall results indicated no
      obvious association of this variant on prostate cancer risk. However, in subgroup
      analysis by ethnicity, positive associations existed in Caucasian descendents for
      allelic contrast (OR = 1.03, 95% CI: 1.00-1.06, pheterogeneity = 0.552, p =
      0.026) and the dominant genetic model (OR = 1.03, 95% CI: 1.00-1.05,
      pheterogeneity = 0.856, p = 0.032). In the subgroup analysis by tumor stage,
      there was a significant association between this variant and advanced prostate
      cancer under the recessive genetic model (OR = 1.15, 95% CI: 1.01-1.32,
      pheterogeneity = 0.469, p = 0.032). In the subgroup analysis by source of
      control, association of the VDR FokI polymorphism and prostate cancer
      susceptibility was also found in population-based studies under homozygote
      comparison and the recessive genetic model. Conclusions: The VDR FokI
      polymorphism may contribute to the risk of developing prostate cancer in
      Caucasian and population-based studies. Further large, well-designed studies are
      warranted to confirm this conclusion in more detail.

PMID- 29181078
TI  - Pain, acceptance of illness, adjustment to life with cancer and coping strategies
      in prostate cancer patients.
AB  - Introduction: Prostate cancer is the second most common type of carcinoma in men.
      The rate of prostate cancer has increased approximately fivefold lover the last
      30 years. The purpose of the study was to evaluate coping strategies, pain
      management, illness acceptance, and adjustment to cancer in patients diagnosed
      with prostate carcinoma and the effect of socioeconomic variables on the above
      mentioned issues. Material and methods: The study included 228 patients diagnosed
      with prostate cancer. The questionnaire interview consisted of demographic
      questions and four psychometric tests: BPCQ, measuring the influence of factors
      affecting pain management, CSQ, designed to evaluate pain coping strategies, the
      AIS questionnaire, measuring disease acceptance, and the Mini-Mac. Results: Pain
      locus of control scores in prostate cancer patients are distributed evenly across
      all three BPCQ subscales. The top mean score was observed in the area of beliefs
      that powerful others (doctors) control pain. Increased behavioral activity was
      the most frequently selected coping strategy (mean score = 18.27). The average
      level of disease acceptance in study patients was 30.39, with a standard
      deviation of 8.07. The results were differentiated by education (p = 0.08) and
      income (p = 0.012). The most frequently indicated coping strategies were fighting
      spirit (mean score = 22.46) and positive re-evaluation (mean score = 22.04).
      Conclusions: The main belief about pain control in prostate cancer patients is
      that powerful others (doctors) control pain. The study patients cope with disease
      constructively. The main socioeconomic variables which differentiate the scores
      obtained across all tests are income and education.

PMID- 29181079
TI  - Survivin expression, HPV positivity and microvessel density in oropharyngeal
      carcinomas and relationship with survival time.
AB  - Introduction: Among head and neck cancers, those of the oral cavity and
      oropharynx are the second most prevalent following the larynx. This study aimed
      to research immunohistochemical expression of survivin, HPV positivity and
      microvessel density in tumors and their relationships with prognosis. Material
      and methods: Pathological materials and demographic properties of 46 patients
      were retrospectively evaluated. Survivin, HPV and CD34 (for microvessel density
      evaluation) antibodies were applied tumoral tissues. Survival times, clinical
      stage and differentiation were evaluated. Results: In univariate analysis, we
      observed that survivin, microvessel density and stage were significantly
      associated with survival time (p < 0.05). In multivariate analysis, only survivin
      and microvessel density were associated with survival time (p < 0.05). But we did
      not find significant correlation between neither tumor differentiation nor HPV
      positivity and survival (p > 0.05). Conclusions: Survivin levels and microvessel
      density were found to be effective prognostic factors and were related to
      survival in oral cavity and oropharyngeal cancers. Treatments targeting survivin
      expression and angiogenesis might be employed against these tumor groups.

PMID- 29181080
TI  - Quality of life of patients from rural and urban areas in Poland with head and
      neck cancer treated with radiotherapy. A study of the influence of selected socio
      demographic factors.
AB  - Introduction: The quality of life (QoL) experienced by cancer patients depends
      both on their state of health and on sociodemographic factors. Tumours in the
      head and neck region have a particularly adverse effect on patients
      psychologically and on their social functioning. Material and methods: The study
      involved 121 patients receiving radiotherapy treatment for head and neck cancers.
      They included 72 urban and 49 rural residents. QoL was assessed using the
      questionnaires EORTC-QLQ-C30 and QLQ-H&N35. The data were analysed using
      statistical methods: a chi2 test for independence and a multinomial logit model.
      Results: The evaluation of QoL showed a strong, statistically significant,
      positive dependence on state of health, and a weak dependence on sociodemographic
      factors and place of residence. Evaluations of financial situation and living
      conditions were similar for rural and urban residents. Patients from urban areas
      had the greatest anxiety about deterioration of their state of health. Rural
      respondents were more often anxious about a worsening of their financial
      situation, and expressed a fear of loneliness. Conclusions: Studying the QoL of
      patients with head and neck cancer provides information concerning the areas in
      which the disease inhibits their lives, and the extent to which it does so. It
      indicates conditions for the adaptation of treatment and care methods in the
      healthcare system which might improve the QoL of such patients. A multinomial
      logit model identifies the factors determining the patients' health assessment
      and defines the probable values of such assessment.

PMID- 29181081
TI  - Care of cancer patients with liver and bone metastases - the place of
      pharmaceutical care in a balanced plan, focused on the patient's needs and goals.
AB  - Metastatic cancer, especially in the growing population of geriatric patients,
      presents a big challenge to these patients, as well as to treatment teams and the
      entire health care system. This article describes some common medical problems
      faced by patients with metastases to liver and bone, and presents a diagnostic
      approach, and therapeutic management of various symptoms, relevant to advanced
      stages of the malignant disease. The article highlights the importance of patient
      education on various aspects of metastatic cancer, and underscores the unique
      position of pharmacists practicing pharmaceutical care, which is particularly
      beneficial in this group of patients with advanced malignancy. Also, this paper
      emphasizes that achieving a proper balance between managing the malignant disease
      and maintaining the patients' quality of life, especially in the elderly
      population, should involve coordinated efforts of the oncology treatment team,
      primary care physicians, pharmacists, therapists and nurses, as well as patients,
      their families and caregivers.

PMID- 29181083
TI  - Primary small-cell carcinoma of the palate - the second case report worldwide.

PMID- 29181082
TI  - SOX10-MITF pathway activity in melanoma cells.
AB  - Melanoma is one of the most dangerous and lethal skin cancers, with a
      considerable metastatic potential and drug resistance. It involves a malignant
      transformation of melanocytes. The exact course of events in which melanocytes
      become melanoma cells remains unclear. Nevertheless, this process is said to be
      dependent on the occurrence of cells with the phenotype of progenitor cells -
      cells characterized by expression of proteins such as nestin, CD-133 or CD-271.
      The development of these cells and their survival were found to be potentially
      dependent on the neural crest stem cell transcription factor SOX10. This is just
      one of the possible roles of SOX10, which contributes to melanomagenesis by
      regulating the SOX10-MITF pathway, but also to melanoma cell survival,
      proliferation and metastasis formation. The aim of this review is to describe the
      broad influence of the SOX10-MITF pathway on melanoma cells.

PMID- 29181084
TI  - Clinical pharmacogenomics: patient perspectives of pharmacogenomic testing and
      the incidence of actionable test results in a chronic disease cohort.
AB  - Aim: This study aimed to examine pharmacogenomic test results and patient
      perspectives at an academic cardiovascular medicine clinic. Patients & methods:
      Test results for three common cardiovascular drug-gene tests (warfarin-CYP2C9
      VKORC1, clopidogrel-CYP2C19 and simvastatin-SLCO1B1) of 208 patients in the Ohio
      State University-Coriell Personalized Medicine Collaborative were examined to
      determine the incidence of potentially actionable test results. A post-hoc,
      anonymous, patient survey was also conducted. Results: Potentially actionable
      test results for at least one of the three drug-gene tests were determined in 170
      (82%) patients. Survey responses (n = 134) suggested that patients generally
      considered their test results to be important (median of 7.5 on a 10-point scale
      of importance) and were interested (median of 7.3 on a 10-point scale of
      interest) in a Clinical Pharmacogenomic Service. Conclusion: Attitudes toward
      pharmacogenomic testing were generally favorable, and potentially actionable test
      results were not uncommon in this cardiovascular medicine cohort.

PMID- 29181085
TI  - Communication challenges for nongeneticist physicians relaying clinical genomic
      results.
AB  - Aim: Identify the behavioral challenges to the use of genome sequencing (GS) in a
      clinical setting. Materials & methods: We observed how general internists and
      nongenetic specialists delivered GS results to patients enrolled in the MedSeq
      Project. Using transcripts of such disclosure interactions, we made qualitative
      observations of communication behaviors that could limit the usefulness of GS
      results until reaching the point of thematic saturation. Results: Findings
      included confusion regarding genomic terminology, difficulty with the volume or
      complexity of information and difficulties communicating complex risk information
      to patients. We observed a broad dismissal of clinical value of GS by some
      physicians and sometimes ineffective communication regarding health behavior
      change. Conclusion: Overcoming these behavioral challenges is necessary to make
      full use of clinical GS results.

PMID- 29181087
TI  - Deep Convolutional Neural Networks for Classifying Body Constitution Based on
      Face Image.
AB  - Body constitution classification is the basis and core content of traditional
      Chinese medicine constitution research. It is to extract the relevant laws from
      the complex constitution phenomenon and finally build the constitution
      classification system. Traditional identification methods have the disadvantages
      of inefficiency and low accuracy, for instance, questionnaires. This paper
      proposed a body constitution recognition algorithm based on deep convolutional
      neural network, which can classify individual constitution types according to
      face images. The proposed model first uses the convolutional neural network to
      extract the features of face image and then combines the extracted features with
      the color features. Finally, the fusion features are input to the Softmax
      classifier to get the classification result. Different comparison experiments
      show that the algorithm proposed in this paper can achieve the accuracy of 65.29%
      about the constitution classification. And its performance was accepted by
      Chinese medicine practitioners.

PMID- 29181089
TI  - Are we enabling the next generation to thrive?

PMID- 29181086
TI  - Recent advances in the development of antiviral therapeutics for Rift Valley
      fever virus infection.
AB  - Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to sub
      Saharan Africa and the Arabian Peninsula and the etiological agent of Rift Valley
      fever. Rift Valley fever is a disease of major public health and economic
      concern, affecting livestock and humans. In ruminants, RVFV infection is
      characterized by high mortality rates in newborns and near 100% abortion rates in
      pregnant animals. Infection in humans is typically manifested as a self-limiting
      febrile illness, but can lead to severe and fatal hepatitis, encephalitis,
      hemorrhagic fever or retinitis with partial or complete blindness. Currently,
      there are no specific treatment options available for RVFV infection. This review
      presents a summary of the therapeutic approaches that have been explored on the
      treatment of RVFV infection.

PMID- 29181088
TI  - Improving detection of mental health problems in community settings in Nepal:
      development and pilot testing of the community informant detection tool.
AB  - Background: Despite increasing efforts to expand availability of mental health
      services throughout the world, there continues to be limited utilization of these
      services by persons with mental illness and their families. Community-based
      detection that facilitates identification and referral of people with mental
      health problems has been advocated as an effective strategy to increase help
      seeking and service utilization. The Community Informant Detection Tool (CIDT)
      was developed for the community informants to identify people with depression,
      psychosis, alcohol use problems, epilepsy, and child behavioral problems in
      community settings. The CIDT has been validated in Nepal and found to be
      effective in promoting treatment initiation. To facilitate replication in other
      settings, this paper describes the development process of CIDT and the steps to
      achieve comprehensibility, utility and feasibility. Methods: The CIDT was
      developed in four steps. First, case vignettes and illustrations were created
      incorporating local idioms of distress for symptoms of each disorder with an
      expert panel of 25 Nepali mental health professionals. Second, the utility of a
      draft tool was assessed through focus group discussions (n = 19) and in-depth
      interviews (n = 6). Third, a practice run was conducted assessing applicability
      of the tool through IDI among purposively selected community informants (n = 8).
      Finally, surveys were administered to 105 community informants to assess
      feasibility. Results: The first through third steps led to modifications in the
      format and presentation of the CIDT. The pilot test found CIDT to be
      comprehensible and feasible for detection and referral of all conditions except
      child behavioral problems. Female community health volunteers were recommended as
      the most appropriate persons to utilize the CIDT. Conclusion: Community-based
      detection using the CIDT for persons in need of mental health care is perceived
      to be useful and feasible by key community stakeholders who would integrate the
      tool into their daily activities.

PMID- 29181090
TI  - Beginner's mind.
AB  - : The concept of 'beginner's mind' invites the expert medical professional to be
      present to their patients, remaining curious and responsive in the face of the
      individuality of illness. Each patient is a universe of unknowns, presenting with
      suffering which cannot always be classified with a diagnosis. Improvisation and
      openness may not just benefit our patients enduring their patient journeys but
      may also revive and reconnect us with our own humanity. Why this matters to me:
      My experience as cancer patient brought home to me the value of encountering a
      doctor who was present and able to listen and respond to me as an individual. It
      did not necessarily take longer, but was about an attitude of heart.Like any
      professional, as GPs we are at risk of presumption and habitual thinking.
      Beginner's mind, that is recapturing the openness and curiosity modelled to us by
      children, can powerfully transform the medical encounter, allowing space for
      emergence of patient perspective and doctor response. Key message: Embrace
      curiosity and learning into our expert clinical practice.

PMID- 29181091
TI  - Parenting and child mental health.
AB  - : This paper reviews parenting programmes and their effectiveness with families
      of young children and highlights additional resources for primary care
      practitioners. Typically, 30% of GP consultations concern child behaviour
      problems and established behaviour problems can have lasting effects on
      children's life chances. These problems can be identified in infancy and
      toddlerhood.Parenting is a key risk factor in their development and maintenance,
      yet is also amenable to change. In this paper we consider six parenting
      programmes that are widely evaluated and/or available in the U.K. and their
      evidence base . These include two NICE recommended parenting programmes
      (Incredible Years and Triple P), which offer tiered and flexible parenting
      programmes; predominantly for parents of school-age children. We also review
      Parent-Infant Psychotherapy, which is typically for parents of younger children.
      Fourth is Family Nurse Partnership, an intensive programme to support young,
      first-time mothers. Finally we consider, video feedback programmes which use
      video to focus in detail on parents' interactions with their children, including
      Video Feedback to Promote Positive Parenting and Video Interactive Guidance.
      These interventions demonstrate the range of approaches which are being used to
      intervene early in children's lives to try to prevent the development of enduring
      behavioural problems. Why this matters to me: It is becoming increasingly clear
      that the origins of many mental health problems lie in childhood. Family factors,
      including the quality of care that parents provide for their children, can make a
      huge difference to children's early life pathways, for better or for worse.
      Understanding how best to intervene to support parents is a key challenge. In
      this article, we critically review the most widely used parenting programmes for
      parents of young children. It is imperative that we judge these early
      interventions to high standards so that we are offering children the best start
      in life. Key message: Parenting programmes offer a means to intercept behaviour
      problems in early childhood before they become established.

PMID- 29181092
TI  - Efficacy of multisystemic therapy in youths aged 10-17 with severe antisocial
      behaviour and emotional disorders: systematic review.
AB  - Background: Antisocial behaviour and conduct disorders are the most common
      behavioural and mental health problems in children and young people globally. An
      efficacious intervention is needed to manage these antisocial behaviours that
      have costly consequences. Multisystemic Therapy (MST), an intensive home-based
      intervention for youths with psychosocial and behavioural problems, is
      recommended under National Institute for Health and Clinical Excellence
      guidelines for conduct disorder. However, reviews on the efficacy of MST are
      mixed. Aim: To review randomised controlled trials (RCTs) reporting efficacy of
      MST among youths presenting with antisocial behaviour and emotional disorder
      respectively. Method: A systematic map term to subject heading search was
      conducted in PsycINFO, Embase, and Ovid Medline databases for articles up to
      November 2015. RCTs comparing MST vs.treatment as usual (TAU) in youths
      presenting with antisocial behaviour and emotional disorder were included.
      Results: 12 RCTs (n = 1425) reported efficacy of MST vs. TAU in youths presenting
      with antisocial behaviour and emotional disorder. Clinically significant
      treatment effects of MST showed a reduction of antisocial behaviour which
      includes delinquency. MST, vs. psychiatric hospitalisation, was associated with a
      reduction of suicidal attempts in youths presenting with psychiatric emergencies.
      4 studies showed that MST was less costly than TAU in the short term, with
      further analysis required for long-term cost-effectiveness. Conclusion: MST is an
      efficacious intervention for severe antisocial behaviours in reduction of
      delinquency and should be included in clinical practices. MST was shown to have a
      positive effect on emotional disorder but further research is needed to evaluate
      the efficacy of MST with emotional disorder. Further analysis is required to
      assess the services utilized for long-term cost effectiveness.

PMID- 29181093
TI  - Preschool growth and nutrition service - addressing common nutritional problems:
      a community based, primary care led intervention.
AB  - Childhood obesity has been prioritised by the World Health Organization in a
      recent report, which calls for a holistic multiagency approach to tackling and
      reducing future risks of obesity and its associated co-morbidities. This article
      examines a health service approach to improving recognition and management of pre
      school nutritional problems as part of training health care professionals. It
      explores the practicalities of setting up a local pathway for managing cases in
      the community with appropriate specialist support. This model, developed for the
      management of weight faltering, has now been adapted to tackle childhood obesity.

PMID- 29181094
TI  - Carelli on art 'The Dali Universe'.
AB  - Interactive and multimedia methods are the future, already developing in teaching
      and learning modules in Medicine. It happens and has to happen because: 1) It
      improves tools for the teacher in preparing and showing the bulk of materials on
      which students must study and learn; it enables interactivity with learners both
      in formative pathway and in final assessment. 2) It improves attention, interest
      and involvement of students and learners, and acts as a guideline to progressive
      broadening in researches, studies, considerations, and information exchanges
      among different learners. 3) The rapid progress in application of technology, WEB
      area and sources researches allows such a deepening and widening interactivity
      that before was never possible to imagine. It is the same thing also in CME,
      sometimes so dry, and dropped from above, while the new methodology may/must get
      rid of negative and boring features, often not useful in producing particular
      improvements in knowledge and quality. The Professional Doctor needs to feel a
      protagonist part in situation to be investigated, where interaction with all what
      media tools can offer may produce an "educative" improvement, much faster,
      effective and pleasant/rewarding.

PMID- 29181095
TI  - Quantitation of Fentanyl Analogs in Dried Blood Spots by Flow-Through Desorption
      Coupled to Online Solid Phase Extraction Tandem Mass Spectrometry.
AB  - An automated dried blood spot (DBS) elution coupled with solid phase extraction
      and tandem mass spectrometric analysis for multiple fentanyl analogs was
      developed and assessed. This method confirms human exposures to fentanyl,
      sufentanil, carfentanil, alfentanil, lofentanil, alpha-methyl fentanyl, and 3
      methyl fentanyl in blood with minimal sample volume and reduced shipping and
      storage costs. Seven fentanyl analogs were detected and quantitated from DBS made
      from venous blood. The calibration curve in matrix was linear in the
      concentration range of 1.0 ng/mL to 100 ng/mL with a correlation coefficient
      greater than 0.98 for all compounds. The limit of detection varied from 0.15
      ng/mL to 0.66 ng/mL depending on target analyte. Analysis of the entire DBS
      minimized the effects of hematocrit on quantitation. All quality control
      materials evaluated resulted in <15% error; analytes with isotopically labeled
      internal standards had <15% RSD, while analytes without matching standards had 15
      24% RSD. This method provides an automated means to detect seven fentanyl
      analogs, and quantitate four fentanyl analogs with the benefits of DBS at levels
      anticipated from an overdose of these potent opioids.

PMID- 29181096
TI  - Structure Activity Relationship of Heparin Mimicking Polymer p(SS-co-PEGMA):
      Effect of Sulfonation and Polymer Size on FGF2-Receptor Binding.
AB  - Fibroblast growth factor-2 (FGF2) is a heparin binding protein that plays a role
      in a range of biological functions such as wound healing and bone regeneration.
      Heparin, a highly sulfated glycosaminoglycan, is required for FGF2 to bind to its
      receptor. Therefore, polymeric mimics of heparin are widely studied for their
      ability to manipulate FGF2-induced biological interactions. It is known that
      altering the degree of sulfonated monomer incorporation and size of heparin
      mimicking polymers can affect protein-receptor binding. To elucidate the
      relationship between degree of sulfonation and receptor binding for the heparin
      mimicking polymer, poly(styrene sulfonate-co-poly(ethylene glycol) methyl ether
      methacrylate) (p(SS-co-PEGMA)) a library was synthesized to contain nine polymers
      with degrees of sulfonation ranging from 0-100%. Kinetics of the polymerization
      was evaluated and reactivity ratios compared to literature results. These
      polymers were then tested for their ability to enhance FGF2 binding with its
      receptor as both covalent conjugates and as excipients. In a receptor based
      enzyme-linked immunosorbant assay (ELISA), as well as a cell-based study, the
      polymer with 81% SS incorporation enhanced receptor binding compared to FGF2
      alone, and to a greater extent than the other polymers. Therefore, another
      library of polymers was prepared maintaining the degree of sulfonation at 81% and
      changing the size from 41 to 390 monomer repeat units. The polymers were again
      tested in receptor based ELISA and cell studies, and all of the different sizes
      performed similarly, except for degree of polymerization 295 and 390, which had
      reduced response in the cellular assay. These results provide important
      information for the use of pSS-co-PEGMA as a potential heparin-mimicking
      therapeutic.

PMID- 29181097
TI  - Stomatin-like protein 2 is overexpressed in cervical cancer and involved in tumor
      cell apoptosis.
AB  - Stomatin-like protein 2 (SLP-2) is overexpressed in numerous types of human
      cancer and previous studies revealed that SLP-2 may function in mitochondria. The
      purpose of the present study was to evaluate the expression of SLP-2 in cervical
      cancer and the association between SLP-2 expression and clinical features, in
      addition to investigating the role of SLP-2 in the apoptosis of cervical cancer
      cells. The expression profile of SLP-2 was determined by quantitative polymerase
      chain reaction, western blotting and immunohistochemical staining. The effect of
      SLP-2 on cell apoptosis induced by chemotherapeutics in cervical cancer cells was
      evaluated using Annexin V staining and terminal deoxynucleotidyl-transferase
      mediated dUTP nick end labeling (TUNEL) assays. The results indicated that SLP-2
      expression in cervical cancer was significantly upregulated at the mRNA and
      protein levels, compared with that in normal cervical tissues.
      Immunohistochemical analysis revealed significant correlation between SLP-2
      protein expression and clinical characteristics, including the squamous cell
      carcinoma antigen (P=0.003), deep stromal invasion (P=0.021), lymphovascular
      space involvement (P=0.044) and pelvic lymph node metastasis (P<0.001), which
      served as independent prognostic factors for predicting the shortening of overall
      survival time in patients with early-stage cervical cancer. In addition, TUNEL
      and Annexin V binding assays revealed that silencing SLP-2 expression
      significantly enhanced the sensitivity of cervical cancer cells to apoptosis
      induced by chemotherapeutics. Taken together, the results of the present study
      suggest that SLP-2 may be a progressive gene in the development of cervical
      cancer. Overexpression of SLP-2 serves an important role in the apoptosis of
      human cervical cancer cells.

PMID- 29181098
TI  - Characterization of hair-follicle side population cells in mouse epidermis and
      skin tumors.
AB  - A subset of cells, termed side-population (SP), which have the ability to efflux
      Hoeschst 33342, have previously been demonstrated to act as a potential method to
      isolate stem cells. Numerous stem/progenitor cells have been localized in
      different regions of the mouse hair follicle (HF). The present study identified a
      SP in the mouse HF expressing the ABCG2 transporter and MTS24 surface marker.
      These cells are restricted to the upper isthmus of the HF and have previously
      been described as progenitor cells. Consistent with their SP characteristic, they
      demonstrated elevated expression of ABCG2 transporter, which participates in the
      dye efflux. Analysis of tumor epidermal cell lines revealed a correlation between
      the number of SP keratinocytes and the grade of malignancy, suggesting that the
      SP may play a role in malignant progression. Consistent with this idea, the
      present study observed an increased number of cells expressing ABCG2 and MTS24 in
      chemically induced skin tumors and skin tumor cell lines. This SP does not
      express the CD34 surface marker detected in the multipotent stem cells of the
      bulge region of the HF, which have been defined as tumor initiation cells. The
      present study concluded that a SP with properties of progenitor cells is
      localized in the upper isthmus of the HF and is important in mouse skin tumor
      progression.

PMID- 29181099
TI  - Breast cancers with EGFR and HER2 co-amplification favor distant metastasis and
      poor clinical outcome.
AB  - ErbB signaling serves essential roles in invasive ductal carcinoma (IDC). The aim
      of the present study was to assess gene amplification in ErbB family members in
      IDC with clinical implications. Quantitative polymerase chain reaction and
      fluorescence in situ hybridization were performed on formalin-fixed paraffin
      embedded tumor samples for gene amplification detection. The clinical and
      histopathological characteristics, as well as the prognostic significance, were
      analyzed. Among the 119 IDC patients evaluated, epidermal growth factor receptor
      [EGFR; also known as human epidermal growth factor receptor (HER)1], HER2, HER3
      and HER4 gene amplification was observed in 30 (25.2%), 44 (36.9%), 0 (0.0%) and
      1 (0.8%) patients, respectively. EGFR amplification was associated with estrogen
      receptor status (P=0.028) and higher possibilities of recurrence (P=0.015) and
      distant metastasis (following initial surgery) (P=0.011). In survival analysis,
      EGFR amplification was also associated with disease-free survival (DFS) (P=0.001)
      and overall survival (OS) (P=0.003). HER2 amplification was associated with
      larger tumor size (P=0.006), later clinical stage (P=0.003) and distant
      metastasis (following initial surgery) (P=0.006). In survival analysis, HER2
      amplification was also associated with DFS (P=0.011). Notably, the present study
      identified a group of patients in whom EGFR and HER2 were co-amplified. This
      group of patients appeared to have a higher possibility of metastasis (when
      diagnosed) (P=0.014) and distant metastasis (following initial surgery)
      (P<0.001). In survival analysis, these patients were noticed to be associated
      with DFS (P<0.001) and OS (P=0.002). With respect to treatment regimen, this was
      also true for the DFS association with chemotherapy (P<0.001), radiotherapy
      (P<0.001) and hormonal therapy (P=0.001). The present results suggest that EGFR
      and HER2 amplification favor distant metastasis following initial surgery and are
      significantly associated with poor clinical outcome in breast cancer patients.

PMID- 29181100
TI  - Kinesin family member 11 contributes to the progression and prognosis of human
      breast cancer.
AB  - The present study aimed to clarify the association between kinesin family member
      11 (KIF11) and human breast cancer, and the effect of KIF11 on breast cancer cell
      progression. Western blot analysis, reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) analysis, retroviral infection, immunohistochemistry
      staining, MTT assay, anchorage-independent growth ability assay and
      tumorigenicity assay were all used in the present study. Western blot and RT-qPCR
      analysis revealed that the expression of KIF11 was markedly increased in
      malignant cells compared with that in non-tumorous cells at the mRNA and protein
      level. Immunohistochemical analysis revealed that KIF11 expression was
      upregulated in 256/268 (95.8%) paraffin-embedded archival breast cancer biopsies.
      Statistical analysis demonstrated a significant association between the
      upregulation of KIF11 expression and the progression of breast cancer.
      Multivariate analysis revealed that KIF11 upregulation represents an independent
      prognostic indicator for the survival of patients with breast cancer.
      Tumorigenicity experiments were further used to evaluate the effect of KIF11 in
      non-obese diabetic/severe combined immunodeficient mice. Silencing endogenous
      KIF11 by short hairpin RNAs inhibited the proliferation of breast cancer cells in
      vitro and in vivo. The present results suggest that KIF11 may serve an important
      function in the proliferation of breast cancer and may represent a novel and
      useful prognostic marker for breast cancer.

PMID- 29181101
TI  - Downregulation of nuclear and cytoplasmic Chibby is associated with advanced
      cervical cancer.
AB  - Chibby has been identified as a putative tumor suppressor and antagonist to beta
      catenin, thereby controlling the Wnt signaling pathway. Chibby is typically
      downregulated in numerous types of cancer and may be associated with
      tumorigenesis. The present study aimed at clarifying the following: i) Whether
      Chibby antagonizes beta-catenin in cervical cancer; ii) whether Chibby and beta
      catenin mRNA expression is associated with cancer progression; and iii) whether
      Chibby and beta-catenin expression may be used as a biomarker. A total of 87
      paraffin-embedded cervical sections with distinct cervical intraepithelial
      neoplasia (CIN) stages (chronic cervicitis, CIN 1, CIN 2, CIN 3 and invasive
      squamous cell carcinoma) were collected between June 2004 and October 2012 The
      mRNA expression level of Chibby and beta-catenin was determined using the
      polymerase chain reaction. Protein expression and cellular localization of Chibby
      and beta-catenin were determined using immunohistochemistry. Chibby and beta
      catenin were analyzed for possible association with the progression of cervical
      cancer. Chibby mRNA expression and the Chibby/beta-catenin ratio were identified
      to be downregulated in invasive tumors. Positive cytoplasmic and nuclear staining
      for Chibby was associated with CIN staging and decreased as the CIN stage
      increased. In addition, the cytoplasmic and membrane intensity of beta-catenin
      was associated with invasive tumors, in which a significantly increased level of
      protein expression was detected. Chibby may be a tumor suppressor in cervical
      cancer, since the dysregulation of Chibby expression is associated with
      tumorigenesis in cervical cancer. Chibby and beta-catenin expression together may
      potentially to a biomarker for disease progression in cervical cancer.

PMID- 29181102
TI  - MicroRNA-1271 inhibits cellular proliferation of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common causes of cancer
      associated mortality worldwide, particularly in China. MicroRNAs (miRs) serve
      important roles in the pathogenesis of HCC. The present study investigated the
      function of miR-1271 in HCC. The miR-1271 levels were analyzed by quantitative
      reverse transcription polymerase chain reaction. Cells growth was examined by MTT
      assay. Bioinformatics algorithms from TargetScanHuman were used to predict the
      target genes of miR-1271. The protein level was assayed by western blotting. miR
      1271 demonstrated a lower expression level in HCC tissues. Upregulation of miR
      1271 suppressed the growth of HepG-2 and Huh-7 cells and induced apoptosis of
      cells. Forkhead box Q1 (FOXQ1) was targeted by miR-1271. In conclusion, miR-1271
      is a novel tumor suppressor that inhibits HCC proliferation and induces cellular
      apoptosis by targeting FOXQ1 in HCC. The results of the present study may provide
      a novel therapeutic target of HCC.

PMID- 29181103
TI  - Myxoid liposarcoma with cartilaginous differentiation showing DDIT3
      rearrangement.
AB  - Myxoid liposarcoma (MLPS) is the second most common histologic subtype of
      liposarcoma. However, cartilaginous differentiation within MLPS is an extremely
      rare phenomenon, with only 7 cases of MLPS with cartilaginous differentiation
      reported to date. The majority of MLPS cases show the t(12;16)(q13;p11)
      translocation, resulting in the fused in sarcoma-DNA damage-inducible transcript
      3 (FUS-DDIT3) fusion gene. This fusion gene as a hallmark of MLPS is very useful
      for differential diagnosis from other soft tissue sarcomas, and the associated
      protein, FUS-DDIT3, performs an important role in the phenotypic selection of
      targeted multipotent mesenchymal cells during oncogenesis. In this report, a case
      of MLPS with cartilaginous differentiation that occurred in the thigh of a 44
      year-old woman is described. Histopathologically, the tumor was composed of a
      typical myxoid liposarcoma area and a mature hyaline cartilaginous area. Using
      fluorescence in situ hybridization analysis, rearrangement of the DDIT3 gene was
      detected in not only the liposarcomatous area but also in the chondrocytes of the
      cartilaginous area. Based on these findings, the cartilaginous differentiation
      area appears to be partially associated with oncogenesis through the specific
      fusion gene FUS-DDIT3.

PMID- 29181104
TI  - Recombinant human adenovirus-p53 improves the outcome of mid-late stage
      pancreatic cancer via arterial infusion.
AB  - The present study aimed to investigate the therapeutic efficacy and clinical
      value of recombinant human adenovirus-p53 (rAd-p53) perfusion via the pancreatic
      artery for the treatment of mid-late stage pancreatic cancer. rAd-p53 (2*1012
      virus particles) in 6 ml normal saline was pushed (intravenous bolus) into the
      gastroduodenal and superior pancreaticoduodenal arteries via interventional
      superselection, with the catheter retained for subsequent drug administration at
      a 3-day interval for 4 cycles. Tumor changes in all patients were observed to
      evaluate tumor response by computed tomography (CT) at 2, 8 and 16 weeks post
      treatment. The following improvements were noted in the 23-patient cohort: A
      total of 73.9% (17/23) of patients demonstrated significant tumor shrinkage
      (>20%); the symptoms of abdominal and back pain were relieved in 15 patients; the
      survival time was >12 months in 1 patient and >6 months in 14 patients; the
      patient's general condition, including appetite, was improved in 13 patients;
      body weight was increased in 9 patients; jaundice was attenuated in 12 patients;
      and ascites subsided in 10 patients. However, the therapeutic outcome was poor in
      2 patients whose tumors size did not show significant change after treatment as
      detected by CT. These 2 patients succumbed within 6 months. In conclusion, rAd
      p53 perfusion via the pancreatic artery is a safe and minimally invasive option
      for the treatment of mid-late stage pancreatic cancer.

PMID- 29181105
TI  - Overexpression of long non-coding RNA colon cancer-associated transcript 2 is
      associated with advanced tumor progression and poor prognosis in patients with
      colorectal cancer.
AB  - The aim of the present study was to explore the clinicopathological and
      prognostic significance of long non-coding RNA (lncRNA) colon cancer-associated
      transcript 2 (CCAT2) expression in human colorectal cancer (CRC). Expression
      levels of lncRNA CCAT2 in CRC, adjacent non-tumor and healthy colon mucosa
      tissues were detected by quantitative polymerase chain reaction. The disease-free
      survival and overall survival rates were evaluated using the Kaplan-Meier method,
      and multivariate analysis was performed using Cox proportional hazard analysis.
      The expression level of lncRNA CCAT2 in CRC tissues was increased significantly
      compared with adjacent normal tissues or non-cancerous tissues. CCAT2 expression
      was observed to be progressively increased between tumor-node-metastasis (TNM)
      stages I and IV. A high level of CCAT2 expression was revealed to be associated
      with poor cell differentiation, deeper tumor infiltration, lymph node metastasis,
      distance metastasis, vascular invasion and advanced TNM stage. Compared with
      patients with low levels of CCAT2 expression, patients with high levels of CCAT2
      expression had shorter disease-free survival and overall survival times.
      Multivariate analyses indicated that high CCAT2 expression was an independent
      poor prognostic factor. Therefore, increased lncRNA CCAT2 expression maybe a
      potential diagnostic biomarker for CRC, and an independent predictor of prognosis
      in patients with CRC.

PMID- 29181106
TI  - ALDH enzyme activity is regulated by Nodal and histamine in the A549 cell line.
AB  - The present study aimed to examine whether the enzyme activity of aldehyde
      dehydrogenase (ALDH) was regulated by Nodal and histamine in the human alveolar
      adenocarcinoma A549 cell line. The regulated enzyme activity of ALDH was analyzed
      by flow cytometry in the A549 cell line. ALDH1 and Nodal expression was
      investigated by immunohistochemistry in28 cases of lung mixed adenocarcinoma. The
      enzyme activity of ALDH was upregulated by histamine and agonists of histamine H1
      receptor (H1R) and histamine H2 receptor (H2R). ALDH activity was also
      downregulated by recombinant human Nodal and antagonists of H1R and H2R in the
      A549 cell line. In addition, expression of Nodal and ALDH1 were inversely
      correlated in lung mixed adenocarcinoma. ALDH enzyme activity was regulated by
      Nodal and histamine in lung adenocarcinoma.

PMID- 29181108
TI  - Comparative profiling of well-defined copper reagents and precursors for the
      trifluoromethylation of aryl iodides.
AB  - A number of copper reagents were compared for their effectiveness in
      trifluoromethylating 4-iodobiphenyl, 4-iodotoluene, and 2-iodotoluene. Yields
      over time were plotted in order to refine our understanding of each reagent
      performance, identify any bottlenecks, and provide more insight into the rates of
      the reactions. Interestingly, differences in reactivity were observed when a well
      defined [LCuCF3] complex was employed directly or generated in situ from
      precursors by published reports. Relative reactivities were also found to highly
      dependent on the nature of the iodoarenes.

PMID- 29181107
TI  - Investigation of fusion gene expression in HCT116 cells.
AB  - Colon cancer is the most common type of gastrointestinal cancer. A number of
      specific and sensitive biomarkers facilitate the diagnosis and monitoring of
      patients with colon cancer. Fusion genes are typically identified in cancer and a
      majority of the newly identified fusion genes are oncogenic in nature. Therefore,
      fusion genes are potential biomarkers and/or therapy targets in cancer. In the
      present study, the regulation of specific candidate fusion genes were
      investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the
      HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator
      CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly
      to the progression of colorectal carcinoma from the M0 to the M1a stage. It was
      identified that EIF3E(e1)-RSPO2(e2), EIF3E(e1)-RSPO2(e3), PTPRK(e1)-RSPO3(e2),
      PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present
      in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a
      genomic fusion transcript, which originates from DNA arrangement in HCT116 cells.
      BORIS suppresses the expression of EIF3E, RSPO2, PTPRK, RSPO3, TADA2A and CD4 to
      inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized
      that the fusion transcripts investigated in the present study may not be
      oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the
      fusion genes investigated may be a biomarker assemblage for monitoring the
      progression of colorectal carcinoma.

PMID- 29181109
TI  - Synthesis and photophysical properties of novel benzophospholo[3,2-b]indole
      derivatives.
AB  - The parent benzophospholo[3,2-b]indole was prepared by the reaction of
      dichlorophenylphosphine with a dilithium intermediate, which was prepared in two
      steps from 2-ethynyl-N,N-dimethylaniline. Using the obtained benzophosphole-fused
      indole as a common starting material, simple modifications were carried out at
      the phosphorus center of the phosphole, synthesizing various functionalized
      analogs. The X-ray structure analysis of trivalent phosphole and phosphine oxide
      showed that the fused tetracyclic moieties are planar. The benzophosphole-fused
      indoles, such as phosphine oxide, phospholium salt, and borane complex, exhibited
      strong photoluminescence in dichloromethane (Phi = 67-75%).

PMID- 29181110
TI  - Diosgenyl 2-amino-2-deoxy-beta-D-galactopyranoside: synthesis, derivatives and
      antimicrobial activity.
AB  - The synthesis of diosgenyl 2-amino-2-deoxy-beta-D-galactopyranoside is presented
      for the first time. This synthetic saponin was transformed into its hydrochloride
      as well as N-acyl, 2-ureido, N-alkyl, and N,N-dialkyl derivatives. Antifungal and
      antibacterial studies show that some of the obtained compounds are active against
      Gram-positive bacteria and Candida type fungi.

PMID- 29181111
TI  - Homologated amino acids with three vicinal fluorines positioned along the
      backbone: development of a stereoselective synthesis.
AB  - Backbone-extended amino acids have a variety of potential applications in peptide
      and protein science, particularly if the geometry of the amino acid is
      controllable. Here we describe the synthesis of delta-amino acids that contain
      three vicinal C-F bonds positioned along the backbone. The ultimately successful
      synthetic approach emerged through the investigation of several methods based on
      both electrophilic and nucleophilic fluorination chemistry. We show that
      different diastereoisomers of this fluorinated delta-amino acid adopt distinct
      conformations in solution, suggesting that these molecules might have value as
      shape-controlled building blocks for future applications in peptide science.

PMID- 29181112
TI  - Synthesis of ergostane-type brassinosteroids with modifications in ring A.
AB  - Herein, we present a new strategy for the preparation of a broad range of
      brassinosteroid biosynthetic precursors/metabolites differing by the ring A
      fragment. The protocol is based on the use of readily available phytohormones of
      this class bearing a 2alpha,3alpha-diol moiety (epibrassinolide or
      epicastasterone) as starting materials. The required functionalities (Delta2-,
      2alpha,3alpha- and 2beta,3beta-epoxy-, 2alpha,3beta-, 2beta,3alpha-, and
      2beta,3beta-dihydroxy-, 3-keto-, 3alpha- and 3beta-hydroxy-, 2alpha-hydroxy-3
      keto-) were synthesized from 2alpha,3alpha-diols in a few simple steps (Corey
      Winter reaction, epoxidation, oxidation, hydride reduction, etc.).

PMID- 29181113
TI  - Is the tungsten(IV) complex (NEt4)2[WO(mnt)2] a functional analogue of acetylene
      hydratase?
AB  - The tungsten(IV) complex (Et4N)2[W(O)(mnt)2] (1; mnt = maleonitriledithiolate)
      was proposed (Sarkar et al., J. Am. Chem. Soc.1997, 119, 4315) to be a functional
      analogue of the active center of the enzyme acetylene hydratase from Pelobacter
      acetylenicus, which hydrates acetylene (ethyne; 2) to acetaldehyde (ethanal; 3).
      In the absence of a satisfactory mechanistic proposal for the hydration reaction,
      we considered the possibility of a metal-vinylidene type activation mode, as it
      is well established for ruthenium-based alkyne hydration catalysts with anti
      Markovnikov regioselectivity. To validate the hypothesis, the regioselectivity of
      tungsten-catalyzed alkyne hydration of a terminal, higher alkyne had to be
      determined. However, complex 1 was not a competent catalyst for the hydration of
      1-octyne under the conditions tested. Furthermore, we could not observe the
      earlier reported hydration activity of complex 1 towards acetylene. A critical
      assessment of, and a possible explanation for the earlier reported results are
      offered. The title question is answered with "no".

PMID- 29181114
TI  - One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones
      by T3P(r) activation of 3-arylpropiolic acids.
AB  - In situ activation of 3-arylpropiolic acids with T3P(r) (n-propylphosphonic acid
      anhydride) initiates a domino reaction furnishing 4-arylnaphtho[2,3-c]furan-1,3
      diones in excellent yields. Upon employing these anhydrides as reactive
      intermediates blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones are
      formed by consecutive pseudo three-component syntheses in a one-pot fashion. The
      Stokes shifts correlate excellently with the Hammett-Taft sigmaR parameter
      indicating an extended degree of resonance stabilization in the vibrationally
      relaxed excited singlet state.

PMID- 29181115
TI  - Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic
      hybrids based on quinoline and 1,2,3-triazole.
AB  - Copper-catalyzed mechanochemical click reactions using Cu(II), Cu(I) and Cu(0)
      catalysts have been successfully implemented to provide novel 6-phenyl-2
      (trifluoromethyl)quinolines with a phenyl-1,2,3-triazole moiety at O-4 of the
      quinoline core. Milling procedures proved to be significantly more efficient than
      the corresponding solution reactions, with up to a 15-fold gain in yield.
      Efficiency of both solution and milling procedures depended on the p-substituent
      in the azide reactant, resulting in H < Cl < Br < I reactivity bias. Solid-state
      catalysis using Cu(II) and Cu(I) catalysts entailed the direct involvement of the
      copper species in the reaction and generation of highly luminescent compounds
      which hindered in situ monitoring by Raman spectroscopy. However, in situ
      monitoring of the milling processes was enabled by using Cu(0) catalysts in the
      form of brass milling media which offered a direct insight into the reaction
      pathway of mechanochemical CuAAC reactions, indicating that the catalysis is most
      likely conducted on the surface of milling balls. Electron spin resonance
      spectroscopy was used to determine the oxidation and spin states of the
      respective copper catalysts in bulk products obtained by milling procedures.

PMID- 29181116
TI  - Fluorination of some highly functionalized cycloalkanes: chemoselectivity and
      substrate dependence.
AB  - A study exploring the chemical behavior of some dihydroxylated beta-amino ester
      stereo- and regioisomers, derived from unsaturated cyclic beta-amino acids is
      described. The nucleophilic fluorinations involving hydroxy-fluorine exchange of
      some highly functionalized alicyclic diol derivatives have been carried out in
      view of selective fluorination, investigating substrate dependence, neighboring
      group assistance and chemodifferentiation.

PMID- 29181117
TI  - Mechanochemistry.

PMID- 29181118
TI  - Structure-property relationships and third-order nonlinearities in
      diketopyrrolopyrrole based D-pi-A-pi-D molecules.
AB  - Nine new quadrupolar chromophores based on diketopyrrolopyrrole were designed and
      prepared by cross-coupling reactions. The property tuning has been achieved by
      structural variation of the peripheral substituents (donor) and enlargement of
      the pi-system. Fundamental properties of target molecules were studied by
      differential scanning calorimetry, electrochemistry, and absorption and emission
      spectra. Nonlinear optical properties were studied by measuring the third
      harmonic generation. The experimental data were completed by quantum-chemical
      calculations and structure-property relationships were elucidated.

PMID- 29181119
TI  - Electron-deficient pyridinium salts/thiourea cooperative catalyzed O
      glycosylation via activation of O-glycosyl trichloroacetimidate donors.
AB  - The glycosylation of O-glycosyl trichloroacetimidate donors using a synergistic
      catalytic system of electron-deficient pyridinium salts/aryl thiourea derivatives
      at room temperature is demonstrated. The acidity of the adduct formed by the 1,2
      addition of alcohol to the electron-deficient pyridinium salt is increased in the
      presence of an aryl thiourea derivative as an hydrogen-bonding cocatalyst. This
      transformation occurs under mild reaction conditions with a wide range of O
      glycosyl trichloroacetimidate donors and glycosyl acceptors to afford the
      corresponding O-glycosides in moderate to good yields with predictable
      selectivity. In addition, the optimized method is also utilized for the
      regioselective O-glycosylation by using a partially protected acceptor.

PMID- 29181120
TI  - Synthesis, effect of substituents on the regiochemistry and equilibrium studies
      of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines.
AB  - An efficient synthesis methodology for a series of tetrazolo[1,5-a]pyrimidines
      substituted at the 5- and 7-positions from the cyclocondensation reaction [CCC +
      NCN] was developed. The NCN corresponds to 5-aminotetrazole and CCC to beta
      enaminone. Two distinct products were observed in accordance with the beta
      enaminone substituent. When observed in solution, the compounds can be divided
      into two groups: (a) precursor compounds with R = CF3 or CCl3, which leads to
      tetrazolo[1,5-a]pyrimidines in high regioselectivity with R at the 7-position of
      the heterocyclic ring; and (b) precursor compounds with R = aryl or methyl, which
      leads to a mixture of compounds, tetrazolo[1,5-a] pyrimidines (R in the 5
      position of the ring) and 2-azidopyrimidines (R in the 4-position of the ring),
      which was attributed to an equilibrium of azide-tetrazole. In the solid state,
      all compounds were found as 2-azidopyrimidines. The regiochemistry of the
      reaction and the stability of the products are discussed on the basis of the data
      obtained by density functional theory (DFT) for energetic and molecular orbital
      (MO) calculations.

PMID- 29181121
TI  - Ginger Oleoresin Alleviated gamma-Ray Irradiation-Induced Reactive Oxygen Species
      via the Nrf2 Protective Response in Human Mesenchymal Stem Cells.
AB  - Unplanned exposure to radiation can cause side effects on high-risk individuals;
      meanwhile, radiotherapies can also cause injury on normal cells and tissues
      surrounding the tumor. Besides the direct radiation damage, most of the ionizing
      radiation- (IR-) induced injuries were caused by generation of reactive oxygen
      species (ROS). Human mesenchymal stem cells (hMSCs), which possess self-renew and
      multilineage differentiation capabilities, are a critical population of cells to
      participate in the regeneration of IR-damaged tissues. Therefore, it is
      imperative to search effective radioprotectors for hMSCs. This study was to
      demonstrate whether natural source ginger oleoresin would mitigate IR-induced
      injuries in human mesenchymal stem cells (hMSCs). We demonstrated that ginger
      oleoresin could significantly reduce IR-induced cytotoxicity, ROS generation, and
      DNA strand breaks. In addition, the ROS-scavenging mechanism of ginger oleoresin
      was also investigated. The results showed that ginger oleoresin could induce the
      translocation of Nrf2 to cell nucleus and activate the expression of
      cytoprotective genes encoding for HO-1 and NQO-1. It suggests that ginger
      oleoresin has a potential role of being an effective antioxidant and
      radioprotective agent.

PMID- 29181123
TI  - Carlina vulgaris L. as a Source of Phytochemicals with Antioxidant Activity.
AB  - The methanol extracts from three populations of Carlina vulgaris L. were examined
      for the chlorogenic acid content, mineral content, total phenolic content (TPC),
      total flavonoid content (TFC), and antioxidant activity. Two populations
      originated from natural nonmetallicolous habitats (NN (populations from Nasilow)
      and NP (populations from Pinczow)), and one metallicolous population (MB) was
      collected from Boleslaw waste heap localized at the place of former open-cast
      mining of Ag-Pb and Zn-Pb ores dating back to the 13th century and 18th century,
      respectively. The level of Zn, Pb, Cd, Fe, Ni, and Mn was significantly higher in
      the root and leaves of MB plants as a result of soil contaminations compared to
      those of the NN and NP ones. The highest antioxidant potency has been showed by
      the plants growing in a nonmetallicolous habitat. The flower head extracts
      obtained from the nonmetallicolous populations also contained the largest amount
      of chlorogenic acid, whereas the lowest was determined in the roots (ca. 2-3.5
      mg/g and 0.2-0.4 mg/g of air-dry weight, resp.). These studies provide important
      information on the influence of a habitat on the quality of herbal materials and
      the content of the biologically active primary and secondary metabolites.

PMID- 29181124
TI  - Inhibition of Caveolae Contributes to Propofol Preconditioning-Suppressed
      Microvesicles Release and Cell Injury by Hypoxia-Reoxygenation.
AB  - Endothelial microvesicles (EMVs), released after endothelial cell (EC) apoptosis
      or activation, may carry many adverse signals and propagate injury by
      intercellular transmission. Caveolae are 50-100 nm cell surface plasma membrane
      invaginations involved in many pathophysiological processes. Recent evidence has
      indicated EMVs and caveolae may have functional effects in cells undergoing H/R
      injury. Propofol, a widely used anaesthetic, confers antioxidative stress
      capability in the same process. But the connection between EMVs, H/R, and
      caveolae remains largely unclear. Here, we found that H/R significantly increased
      the release of EMVs, the expression of CAV-1 (the structural protein responsible
      for maintaining the shape of caveolae), oxidative stress, and the mitochondrial
      damage, and all these changes were inhibited by propofol preconditioning.
      Interestingly, the caveolae inhibitor Mbeta-CD strengthened the protective effect
      of propofol preconditioning. We further found that the release of EMVs is more
      significantly reduced under propofol preconditioning in the presence of the
      caveolae inhibitor Mbeta-CD. EMVs released from H/R-treated cells caused a
      substantially increased mitochondrial and cellular damage to normal HUVECs after
      4 hours of coculture. Thus, we conclude that inhibition of caveolae contributes
      to propofol preconditioning-suppressed microvesicles release and cell injury by
      H/R.

PMID- 29181122
TI  - Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the
      Complex Milieu of Anthracycline Cardiotoxicity.
AB  - The production of reactive species is a core of the redox cycling profile of
      anthracyclines. However, these molecular characteristics can be viewed as a
      double-edged sword acting not only on neoplastic cells but also on multiple
      cellular targets throughout the body. This phenomenon translates into
      anthracycline cardiotoxicity that is a serious problem in the growing population
      of paediatric and adult cancer survivors. Therefore, better understanding of
      cellular processes that operate within but also go beyond cardiomyocytes is a
      necessary step to develop more effective tools for the prevention and treatment
      of progressive and often severe cardiomyopathy experienced by otherwise
      successfully treated oncologic patients. In this review, we focus on oxidative
      stress-triggered cellular events such as DNA damage, senescence, and cell death
      implicated in anthracycline cardiovascular toxicity. The involvement of
      progenitor cells of cardiac and extracardiac origin as well as different cardiac
      cell types is discussed, pointing to molecular signals that impact on cell
      longevity and functional competence.

PMID- 29181125
TI  - Protective Effects and Possible Mechanisms of Ergothioneine and Hispidin against
      Methylglyoxal-Induced Injuries in Rat Pheochromocytoma Cells.
AB  - Diabetic encephalopathy (DE) is often a complication in patients with Alzheimer's
      disease due to high blood sugar induced by diabetic mellitus. Ergothioneine (EGT)
      and hispidin (HIP) are antioxidants present in Phellinus linteus. Methylglyoxal
      (MGO), a toxic precursor of advanced glycated end products (AGEs), is responsible
      for protein glycation. We investigated whether a combination EGT and HIP (EGT +
      HIP) protects against MGO-induced neuronal cell damage. Rat pheochromocytoma
      (PC12) cells were preincubated with EGT (2 MUM), HIP (2 MUM), or EGT + HIP, then
      challenged with MGO under high-glucose condition (30 MUM MGO + 30 mM glucose; GLU
      + MGO) for 24-96 h. GLU + MGO markedly increased protein carbonyls and reactive
      oxygen species in PC12 cells; both of these levels were strongly reduced by EGT
      or HIP with effects comparable to those of 100 nM aminoguanidine (an AGE
      inhibitor) but stronger than those of 10 MUM epalrestat (an aldose reductase
      inhibitor). GLU + MGO significantly increased the levels of AGE and AGE receptor
      (RAGE) protein expression of nuclear factor kappa-B (NF-kappaB) in the cytosol,
      but treatment with EGT, HIP, or EGT + HIP significantly attenuated these levels.
      These results suggest that EGT and HIP protect against hyperglycemic damage in
      PC12 cells by inhibiting the NF-kappaB transcription pathway through antioxidant
      activities.

PMID- 29181126
TI  - Rhinacanthin C Alleviates Amyloid-beta Fibrils' Toxicity on Neurons and
      Attenuates Neuroinflammation Triggered by LPS, Amyloid-beta, and Interferon-gamma
      in Glial Cells.
AB  - Neuroinflammation plays a central role in the pathophysiology of Alzheimer's
      disease (AD). Compounds that suppress neuroinflammation have been identified as
      potential therapeutic targets for AD. Rhinacanthin C (RC), a naphthoquinone ester
      found in Rhinacanthus nasutus Kurz (Acanthaceae), is currently proposed as an
      effective molecule against inflammation. However, the exact role of RC on
      neuroinflammation remains to be elucidated. In the present study, we investigated
      RC effect on modulating lipopolysaccharides (LPS), amyloid-beta peptide (Abeta),
      or interferon-gamma- (IFN-gamma-) evoked pathological events in neurons and glia.
      Our findings demonstrated that RC prevented Abeta-induced toxicity in rat
      hippocampal neurons and attenuated LPS-activated nitric oxide (NO) production,
      inducible nitric oxide synthase (iNOS) expression, and NF-kappaB signaling in rat
      glia. Likewise, RC suppressed LPS-induced neuroinflammation by reducing NO
      production and iNOS, IL-1beta, CCL-2, and CCL-5 mRNA levels in rat microglia.
      Further studies using BV-2 microglia revealed that RC inhibited LPS-, Abeta-, and
      IFN-gamma-stimulated IL-6 and TNF-alpha secretion. Of note, NF-kappaB and ERK
      activation was abrogated by RC in BV-2 cell response to Abeta or IFN-gamma.
      Moreover, RC protected neurons from Abeta-stimulated microglial conditioned media
      dependent toxicity. Collectively, these data highlight the beneficial effects of
      RC on neuroprotection and support the therapeutic implications of RC to
      neuroinflammation-mediated conditions.

PMID- 29181127
TI  - Oxidative Modification of Blood Serum Proteins in Multiple Sclerosis after
      Interferon Beta and Melatonin Treatment.
AB  - Multiple sclerosis (MS) is a disease involving oxidative stress (OS). This study
      was aimed at examination of the effect of melatonin supplementation on OS
      parameters, especially oxidative protein modifications of blood serum proteins,
      in MS patients. The study included 11 control subjects, 14 de novo diagnosed MS
      patients with the relapsing-remitting form of MS (RRMS), 36 patients with RRMS
      receiving interferon beta-1b (250 MUg every other day), and 25 RRMS patients
      receiving interferon beta-1b plus melatonin (5 mg daily). The levels of N'
      formylkynurenine, kynurenine, dityrosine, carbonyl groups, advanced glycation
      products (AGEs), advanced oxidation protein products (AOPP), and malondialdehyde
      were elevated in nontreated RRSM patients. N'-Formylkynurenine, kynurenine, AGEs,
      and carbonyl contents were decreased only in the group treated with interferon
      beta plus melatonin, while dityrosine and AOPP contents were decreased both in
      the group of patients treated with interferon beta and in the group treated with
      interferon beta-1b plus melatonin. These results demonstrate that melatonin
      ameliorates OS in MS patients supporting the view that combined administration of
      interferon beta-1b and melatonin can be more effective in reducing OS in MS
      patients than interferon beta-1b alone.

PMID- 29181128
TI  - Telomere shortening in non-tumorous and tumor mucosa is independently related to
      colorectal carcinogenesis in precancerous lesions.
AB  - Telomere shortening is associated with colorectal carcinogenesis and recent
      studies have focused on its characteristics in both normal mucosa and tumor
      tissues. To clarify the role of telomeres in colorectal carcinogenesis, we
      analyzed telomere shortening in normal and tumor regions of 93 colorectal
      precursor lesions. Telomere length was examined in 61 tubular adenomas (TAs) and
      32 serrated polyps (SPs), and PIK3CA expression, KRAS mutation, BRAF mutation,
      and MSI were also analyzed. Telomere length was similar in normal and tumor
      tissues of TAs and SPs. In normal tissues of TAs, telomere shortening was
      associated with PIK3CA amplification (81.3% vs. 18.8%, p < 0.001), whereas it was
      associated with BRAF mutation in normal tissues of SPs (66.7% vs. 23.1%, p =
      0.060). According to the analysis on tumor tissues, KRAS and BRAF mutations were
      mutually exclusive in TAs and SPs (p < 0.001), and telomere shortening was
      associated with mitochondrial microsatellite instability (63.6% vs. 36.4%, p =
      0.030). These data suggested a pivotal role of telomere shortening in normal
      colorectal tissue for proceeding to TAs or SPs along with PIK3CA amplification
      and BRAF mutation, respectively. Moreover, telomeres in TAs may collaborate with
      mitochondrial instability for disease progression.

PMID- 29181129
TI  - Erratum: pri-miR-34b/c rs4938723 polymorphism is associated with hepatocellular
      carcinoma risk: a case-control study in a Chinese population.
AB  - [This corrects the article on p. 1 in vol. 8, PMID: 28337312.].

PMID- 29181130
TI  - Palmar Nerve Sheath Myxoma: A Case Report.
AB  - Nerve sheath myxoma is a rare benign tumor of the peripheral nerves. It typically
      presents as a painless, firm, and slow growing nodule with a predilection for
      extremities mostly fingers and knees. Microscopically, it has characteristic
      multilobules of spindle cells in an abundant myxoid stroma. The cells are
      strongly positive for S-100 protein. However, this rare tumor is usually
      misdiagnosed as other more common benign neuronal tumors. This report describes a
      rare case of nerve sheath myxoma involving the palmar surface of a 23-year-old
      female. Clinically, it was diagnosed as a fibroma. It was excised and the final
      diagnosis was made after histopathological and comprehensive immunohistochemical
      examination of the specimen. The clinicopathological features of this rare tumor
      and its important differential diagnoses are discussed along with a brief review
      of the literature.

PMID- 29181131
TI  - Pressure Sore at an Unusual Site- the Bilateral Popliteal Fossa: A Case report.
AB  - Pressure sore is tissue ulceration due to unrelieved pressure, altered sensory
      perception, and exposure to moisture. Geriatric patients with organic problems
      and patients with spinal cord injuries are the high-risk groups. Soft tissues
      over bony prominences are the common sites for ulcer development. About 95% of
      pressure ulcers occur in the lower part of the body. Ischial tuberosity, greater
      trochanter, sacrum and heel are common sites. In addition to these, pressure
      sores at unusual sites like nasal alae, malar eminences, cervical region and
      medial side of knee have also been described. Only 1.6% of the patients present
      with sores in areas outside the pelvis and lower extremity. In a paraplegic
      patient, pressure sores are usually over extensor surface of knee and heel but
      pressure ulcer over popliteal fossa are extremely rare. We herein report a case
      of a 36-years-old diabetic and paraplegic male, who presented with multiple bed
      sores involving the sacral area, heels and bilateral popliteal fossa. Popliteal
      fossa is an unusual site for pressure sores. Only one similar case has been
      previously reported in the literature.

PMID- 29181132
TI  - Giant Cell Fibroblastoma: A Case Report.
AB  - Giant cell fibroblastoma is a rare intermediate grade soft tissue tumor of
      childhood which characteristically occurs in males during the first decade of
      life. It has high incidence of local recurrence but metastasis has never been
      reported. Giant cell fibroblastoma merits attentive interpretation as they have
      been misdiagnosed as sarcoma in the past leading to erroneous remedies. Here we
      are reporting a case of giant cell fibroblastoma in a 3-year-old boy who
      presented with a painless swelling over the medial aspect of right ankle forthe
      last five months.

PMID- 29181133
TI  - Use of dark chocolate for diabetic patients: a review of the literature and
      current evidence.
AB  - Dietary changes are a major lifestyle factor that can influence the progression
      of chronic diseases such as diabetes. Recently, flavanols, a subgroup of plant
      derived phytochemicals called flavonoids, have gained increasing attention, due
      to studies showing an inverse correlation between dietary intake of flavanols and
      incidence of diabetes. Flavanoids in the cocoa plant may ameliorate insulin
      resistance by improving endothelial function, altering glucose metabolism, and
      reducing oxidative stress. Oxidative stress has been proposed as the main culprit
      for insulin resistance. The well-established effects of cocoa on endothelial
      function also points to a possible effect on insulin sensitivity. The
      relationship between insulin resistance and endothelial function is a reciprocal
      one. Overall, the evidence from these studies suggests that cocoa may be useful
      in slowing the progression to type 2 diabetes and ameliorating insulin resistance
      in metabolic syndrome. Additionally, results from several small studies indicate
      that cocoa may also have therapeutic potential in preventing cardiovascular
      complications in diabetic patients. Studies highlighting the potential of cocoa
      containing diets, in large-randomized controlled trials should be performed which
      might give us a better opportunity to analyze the potential health-care benefit
      for reducing the risk of complications in diabetic patients at molecular level.

PMID- 29181134
TI  - A nine-month-old-boy with Atypical Hemophagocytic Lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammation
      caused by uncontrolled proliferation of activated lymphocytes and histiocytes.
      Often, HLH is an acquired syndrome. We report a case of a nine month-old-boy
      presented with hepatosplenomegaly, severe anemia, thrombocytopenia,
      hypertriglyceridemia and high hyperferritinemia. These clinical features of HLH
      prompted a wide range of infectious and auto-immune tests to be performed. After
      an extensive diagnostic workup, he was referred to the immune-hematologic unit
      for HLH suspicion with an unknown cause. Primary HLH due to familial
      lymphohistiocytosis (FLH) was first evoked in front of consanguinity, probable
      HLH in the family, early onset, and in the absence of a causative pathology like
      infection or cancer. However, functional tests were normal. Atypical features
      like the: absence of fever, hypotonia, recurrent diarrhea since diversification,
      hematuria, and proteinuria suggested an inborn metabolism error with
      gastrointestinal involvement. Specific tests were performed to reach a final
      diagnosis.

PMID- 29181135
TI  - Graves' Disease Thyrotoxicosis and Propylthiouracil Related Agranulocytosis
      Successfully Treated with Therapeutic Plasma Exchange and G-CSF Followed by Total
      Thyroidectomy.
AB  - Antithyroid drugs can be a rare cause of agranulocytosis (0.5% of treated
      patients). Suspension of these drugs is mandatory in these patients and may
      result in worsening hyperthyroidism. We report the case of a 27-year-old woman
      who is 3 months post-partum, breastfeeding, and suffering with Graves' disease
      hyperthyroidism treated first with methimazole and then with propylthiouracil due
      to a methimazole allergy. She was admitted for urosepsis and agranulocytosis. The
      patient was diagnosed with propylthiouracil related agranulocytosis, diffuse
      toxic goiter and thyro-gastric syndrome. Antithyroid drug therapy was stopped
      resulting in a worsening of thyrotoxicosis. Agranulocytosis was treated with 8
      doses of G-CSF with full recovery. To rapidly restore euthyroidism and to perform
      a thyroidectomy, the patient received 6 therapeutic plasma exchange (TPE)
      procedures, to clear thyroid hormones and anti-TSH receptor antibodies from
      blood, resulting in a pre-surgical euthyroid state without antithyroid drug
      therapy. Two years after thyroidectomy, the patient is well under thyroid hormone
      replacement therapy with a normal granulocyte count.

PMID- 29181136
TI  - Feasibility and Effectiveness of Tuberculosis Active Case-Finding among Children
      Living with Tuberculosis Relatives: a Cross-Sectional Study in Guinea-Bissau.
AB  - Background and objectives: The World Health Organization End tuberculosis (TB)
      Strategy, approved in 2014, aims at a 90% reduction in TB deaths and an 80%
      reduction in TB incidence rate by 2030. One of the suggested interventions is the
      systematic screening of people with suspected TB, belonging to specific risk
      groups. The Hospital Raoul Follereau (HRF) in Bissau, Guinea-Bissau, is the
      National Reference Hospital for Tuberculosis and Lung Disease of the country. We
      performed an active case-finding program among pediatric age family members and
      cohabitants of admitted adult TB patients, from January to December 2013.
      Methods: Newly admitted adult patients with a diagnosis of TB were invited to
      bring their family members or cohabitants in childhood age for clinical
      evaluation in a dedicated outpatient setting within the hospital compound. All
      the children brought to our attention underwent a medical examination and chest x
      ray. In children with clinical and/or radiologic finding consistent with
      pulmonary TB, a sputum-smear was requested. Results: All admitted adult patients
      accepted to bring their children cohabitants. In total, 287 children were
      examined in 2013. Forty-four patients (15%) were diagnosed with TB. The number
      needed to screen (NNS) to detect one case of TB was 7. 35 patients (80%) had
      pulmonary TB; 2 of them were sputum smear-positive. No adjunctive personnel cost
      was necessary for the intervention. Conclusions: A hospital-based TB active case
      finding program targeted to high-risk groups like children households of severely
      ill admitted patients with TB can successfully be implemented in a country with
      limited resources.

PMID- 29181137
TI  - Transfusion-Related Acute Lung Injury (TRALI) in two Thalassaemia Patients Caused
      by the Same Multiparous Blood Donor.
AB  - We report two separate episodes of transfusion-related acute lung injury (TRALI)
      in two thalassaemia patients who received red blood cell transfusions from the
      same multiparous donor. Both cases had the same symptomatology and occurred
      within 60 minutes of transfusion. The patients presented dyspnoea, sweating,
      fatigue, dizziness, fever, and sense of losing consciousness. The chest x-ray
      showed a pulmonary oedema-like picture with both lungs filled with fluid. The
      patients were treated in the intensive therapy unit. They were weaned off the
      ventilator and discharged following hospitalization 7 and 9 days respectively.
      The TRALI syndrome was diagnosed to be associated with HLA-specific donor
      antibodies against mismatched HLA-antigens of the transfused patients.
      Haemovigilance improvements are essential for reducing the morbidity and
      mortality in transfused patients. Blood from multiparous donors should be tested
      for the presence of IgG HLA-Class I and -Class II antibodies before being
      transfused in thalassaemia and other chronically transfused patients.

PMID- 29181138
TI  - Bing-Neel Syndrome: Illustrative Cases and Comprehensive Review of the
      Literature.
AB  - The Bing-Neel syndrome is a rare neurological complication of Waldenstrom's
      Macroglobulinemia which results from a direct involvement of central nervous
      system by malignant lymphoplasmacytic cells. The clinical suspicion of Bing-Neel
      syndrome may be overlooked because neurologic symptoms are heterogeneous,
      nonspecific and sometimes underhand. A definitive diagnosis of Bing-Neel syndrome
      can be confidently made using brain and spinal cord magnetic resonance imaging as
      well as histopathology and/or cerebrospinal fluid analysis to confirm the
      neoplastic infiltration of central nervous system. The detection in the
      cerebrospinal fluid of patients with Bing-Neel syndrome of the MYD88 (L265P)
      somatic mutation, which is highly recurrent in Waldenstrom's Macroglobulinemia,
      proved useful for the diagnosis and monitoring of central nervous system
      involvement. Despite recommendations recently published, there is still no clear
      consensus on treatment of Bing-Neel syndrome, which includes systemic
      immunochemotherapy, intrathecal chemotherapy and brain irradiation as possible
      options. Ibrutinib, a Bruton kinase inhibitor approved for Waldenstrom's
      Macroglobulinemia, has been recently added to the therapeutic armamentarium of
      Bing-Neel syndrome due to its ability to pass the blood-brain barrier. However,
      prospective clinical trials are eagerly awaited with the aim to define the
      optimal treatment strategy. Here we describe four illustrative cases of Bing-Neel
      syndrome diagnosed and treated at our Institution and review the literature on
      this topic.

PMID- 29181139
TI  - Outcome of Frontline Treatment with "Generic" Imatinib In Adult Patients with
      Chronic Myeloid Leukemia in Algerian Population: A Multicenter Study.
AB  - Introduction: In a developing country like Algeria, such expensive therapy is not
      available. Alternative approaches are needed to help these adult. In Algeria
      'imatib' (CIPLA-India) was introduced in 2006; but no study has been published
      yet in the North Africa region regarding response and outcome of this copy in CML
      patients. The goal of this multicenter study is to characterize newly adult CML
      in the western region of Algeria and to assess the effectiveness and safety of
      imatib (IM, copy) as frontline therapy for patients with CML. Patients and
      Methods: The study was carried out in 7 hematology centers in the western
      Algeria. Patients, who were diagnosed to be suffering from CML between January
      1st, 2007 and December 31st, 2014 were selected for data analysis. All patients
      received a copy preparation, consisting of the alpha crystal form of imatinib,
      (IM, copy) at an oral dose of 400 mg daily and monitored for tolerance and side
      effects while on therapy. Results: Between January 2007 and December 2014, 355
      patients with CML were treated with imatib (Copy). The median follow- up of the
      study was 46 months (range: 13-107 months). Complete hematological response (CHR)
      was seen in 83% of patients within 3 months. According to the Sokal score, 72%
      patients with low, 78% with intermediate and 69% with high risk disease achieved
      a CHR in 3 months (p=0.26) and according to the EUTOS score, 81% of patients with
      low and 70% with high risk disease achieved a CHR in 3 months (p=0.08). The major
      molecular response (MMR) at six months (M6), M9, M12, M18 and M24 was 21%, 38%,
      35%, 51% and 67% respectively and 34% of patients achieved a complete molecular
      response (CMR). The projected 5-year overall survival (OS) rate was 83%. Side
      effects of imatib (copy) in this study were similar to those reported previously
      for the entire imatinib mesylate treatment study and only 8% of patients were
      intolerant to imatib (copy) and treated with a second generation of BCR-ABL
      inhibitor. Conclusion: This study reflects real world experience treating
      patients with CML in a developing country and thus sheds light on differences in
      this population compared to Western countries. In conclusion, imatib (copy) is
      effective and safe in treating patients with CML in chronic phase and proves to
      have a durable outcome. To our knowledge this is the first study reporting the
      response to imatib (copy) in an Algerian population.

PMID- 29181140
TI  - Foetal Haemoglobin and Disease Severity in Nigerian Children with Sickle Cell
      Anaemia.
AB  - Background: Foetal haemoglobin (HbF) is a major modifying factor influencing
      sickle cell disease (SCD) severity. Despite this, HbF estimation is not routinely
      done in Nigeria. The relationship between HbF and SCD severity among affected
      children is also poorly studied. Methods: In this descriptive cross-sectional
      study, we determined the relationship between steady state HbF levels and disease
      severity of Nigerian children aged 1 - 15 years with homozygous SCD. For each
      child, the socio-demographic characteristics and SCD clinical severity were
      determined. The latter was assessed based on the frequency of significant painful
      episodes, blood transfusion, and hospitalisation in the preceding 12 months;
      lifetime cumulative incidence of SCD-related complications; the degree of splenic
      and hepatic enlargement; current haematocrit and leucocyte count. Foetal
      haemoglobin levels were quantified with high-performance liquid chromatography.
      Results: The mean HbF level of the 105 children with SCA was 9.9 +/- 6.0%. Male
      had significantly lower mean HbF levels than females, 8.0 +/- 5.6% vs. 12.2 +/-
      5.8% (p < 0.001). None of the children had severe disease. However, the 32
      children with moderate disease had significantly lower mean foetal haemoglobin
      levels than the 73 with mild disease (7.7 +/- 5.6% vs 10.8 +/- 6.0%
      respectively). The mean HbF level was also significantly lower in children who
      had a history of acute chest syndrome and stroke compared to those without these
      complications, p = 0.002 and 0.010 respectively. Conclusion: Children with SCA
      who had a moderate disease and those with a history of life-threatening
      complications such as stroke and acute chest syndrome had significantly low HbF
      levels. Therefore, it is recommended that facilities for early quantification of
      foetal haemoglobin and HbF inducement were made available to reduce the morbidity
      and mortality among these children.

PMID- 29181141
TI  - Correlation to FVIII:C in Two Thrombin Generation Tests: TGA-CAT and INNOVANCE
      ETP.
AB  - Introduction: Several thrombin-generation tests are available, but few have been
      directly compared. Our primary aim was to investigate the correlation of two
      thrombin generation tests, thrombin generation assay-calibrated automated
      thrombogram (TGA-CAT) and INNOVANCE ETP, to factor VIII levels (FVIII:C) in a
      group of patients with hemophilia A. The secondary aim was to investigate inter
      laboratory variation for the TGA-CAT method. Methods: Blood samples were taken
      from 45 patients with mild, moderate and severe hemophilia A. The TGA-CAT method
      was performed at both centers while the INNOVANCE ETP was only performed at the
      Stockholm center. Correlation between parameters was evaluated using Spearman's
      rank correlation test. For determination of the TGA-CAT inter-laboratory
      variability, Bland-Altman plots were used. Results: The correlation for the
      INNOVANCE ETP and TGA-CAT methods with FVIII:C in persons with hemophilia (PWH)
      was r=0.701 and r=0.734 respectively.The correlation between the two methods was
      r=0.546.When dividing the study material into disease severity groups (mild,
      moderate and severe) based on FVIII levels, both methods fail to discriminate
      between them.The variability of the TGA-CAT results performed at the two centers
      was reduced after normalization; before normalization, 29% of values showed less
      than +/-10% difference while after normalization the number increased to 41%.
      Conclusions: Both methods correlate in an equal manner to FVIII:C in PWH but show
      a poor correlation with each other. The level of agreement for the TGA-CAT method
      was poor though slightly improved after normalization of data. Further
      improvement of standardization of these methods is warranted.

PMID- 29181142
TI  - Molecular Screening for Malaria among Blood Donors in a WHO Claimed Region of
      Egypt, Fayoum Governorate.
AB  - Background: Transfusion-transmitted malaria is undoubtedly a potential health
      hazard for blood recipients. Egypt is still on the prevention of reintroduction
      phase of malaria control program. Fayoum Governorate is considered one of the
      high-risk foci in Egypt due to its geology. However, no studies have been
      reported to evaluate the current status of subclinical Plasmodium infection based
      on sensitive molecular techniques. Moreover, screening of malaria is not listed
      within screening protocols of blood-borne pathogens in Fayoum blood banks.
      Objective: To assess the current prevalence of subclinical Plasmodium infection
      among blood donors of Fayoum inhabitants for transfusion biosafety. To predict
      any possibility of the reemergence of malaria in the governorate and the
      effectiveness of malaria control measures. Methods: A cross-sectional survey was
      conducted on 400 apparently healthy blood-donors in blood transfusion center of
      Fayoum University hospital from Jun 2012 to Jan 2013. Conventional PCR was used
      to detect the 18 S ssrRNA Plasmodium gene. Results: All Fayoum inhabitants' blood
      donors' samples were negative for Plasmodium infection. Conclusions: Current
      applied control, and preventive measures are valid in the context of blood
      transfusion biosafety in Fayoum blood banks and, therefore, the implementation of
      a routine malaria screening test in Fayoum blood banks is not merited at this
      time.

PMID- 29181143
TI  - Myeloid Neoplasms with Isolated Isochromosome 17q: a yet to be Defined Entity.
AB  - Myeloid neoplasms with isolated isochromosome 17q [MN i(17q)] has been described
      as a distinct entity with poor prognosis. However, literature reports show a
      considerable clinical and molecular heterogeneity. We describe a 58-year-old male
      patient who was diagnosed as refractory anemia with multilineage dysplasia and
      ringed sideroblasts with isolated i(17q). Though he initially responded well to
      erythropoietin, he gradually progressed to an aggressive form of MDS/MPN
      refractory to azacytidine and died 29 months after the first diagnosis. Notably,
      in contrast to disease advancement, his karyotype reverted to normal, whereas his
      mutational profile remained unchanged. To our knowledge, this is the first report
      of karyotype normalization during disease progression in patients with MN i(17q).
      It suggests that the i(17q) anomaly is dispensable for the leukemic
      transformation and highlighting the underlying clinical and molecular complexity
      which both has to be resolved before the establishment of MN with isolated i(17q)
      as a distinct entity.

PMID- 29181145
TI  - The Impact of Diagnostic Code Misclassification on Optimizing the Experimental
      Design of Genetic Association Studies.
AB  - Diagnostic codes within electronic health record systems can vary widely in
      accuracy. It has been noted that the number of instances of a particular
      diagnostic code monotonically increases with the accuracy of disease phenotype
      classification. As a growing number of health system databases become linked with
      genomic data, it is critically important to understand the effect of this
      misclassification on the power of genetic association studies. Here, I
      investigate the impact of this diagnostic code misclassification on the power of
      genetic association studies with the aim to better inform experimental designs
      using health informatics data. The trade-off between (i) reduced
      misclassification rates from utilizing additional instances of a diagnostic code
      per individual and (ii) the resulting smaller sample size is explored, and
      general rules are presented to improve experimental designs.

PMID- 29181144
TI  - Evaluation of Electrospun Nanofiber-Anchored Silicone for the Degenerative
      Intervertebral Disc.
AB  - The nucleus pulposus (NP) substitution by polymeric gel is one of the promising
      techniques for the repair of the degenerative intervertebral disc (IVD). Silicone
      gel is one of the potential candidates for a NP replacement material. Electrospun
      fiber anchorage to silicone disc, referred as ENAS disc, may not only improve the
      biomechanical performances of the gel but it can also improve restoration
      capability of the gel, which is unknown. This study successfully produced a novel
      process to anchor any size and shape of NP gel with electrospun fiber mesh.
      Viscoelastic properties of silicone and ENAS disc were measured using standard
      experimental techniques and compared with the native tissue properties. Ex vivo
      mechanical tests were conducted on ENAS disc-implanted rabbit tails to the
      compare the mechanical stability between intact and ENAS implanted spines. This
      study found that viscoelastic properties of ENAS disc are higher than silicone
      disc and comparable to the viscoelastic properties of human NP. The ex vivo
      studies found that the ENAS disc restore the mechanical functionality of rabbit
      tail spine, after discectomy of native NP and replacing the NP by ENAS disc.
      Therefore, the PCL ENF mesh anchoring technique to a NP implant can have clinical
      potential.

PMID- 29181146
TI  - Metastatic prostate adenocarcinoma to intradural foramen magnum.
AB  - Intradural metastatic tumors are rarely reported in foramen magnum (FM),
      including cases of melanoma, pituitary carcinoma, thyroid carcinoma, and prostate
      carcinoma metastases. We report a 68-year-old male who presented with right-sided
      headache, progressive swallowing difficulty requiring gastrostomy tube and
      hoarseness over the course of 1 year. Images revealed a heterogeneous, contrast
      enhancing lesion in the FM that compressed the anterior aspect of the medulla and
      upper spinal cord. Although metastatic tumor was considered in differential
      diagnosis, presumptive diagnosis was FM meningioma due to lack of bone
      destruction or sclerosis on CT and T2W isointense and T1W hypointense appearance
      on MRI. The patient underwent gross total resection via right far-lateral
      transcondylar approach. Histopathological examination revealed prostate carcinoma
      metastasis. To the best of our knowledge this is the second case report of an
      intradural prostate carcinoma metastasis in the FM.

PMID- 29181147
TI  - A unique case of popliteal artery transection after a motorcycle collision.
AB  - Popliteal artery injuries may have devastating consequences if not recognized in
      a timely fashion. The risk of delayed diagnosis of a vascular injury is
      particularly high in blunt trauma to the lower extremity. We present a case of
      popliteal artery injury that is unusual in two respects: severity (a complete
      transection in the setting of a blunt injury) and lack of clinical and
      radiographic signs of the commonly associated musculoskeletal injuries.

PMID- 29181148
TI  - Abdominal compartment syndrome due to spontaneous rectus sheath hematoma with
      extension into the retroperitoneal space.
AB  - Rectus sheath hematoma (RSH) is an increasingly common clinical condition in our
      hospitals due to the increasing use of anticoagulant therapies for various
      purposes among our patients. Treatment of spontaneous RSH is generally
      conservative. For continued bleeding, interventional radiologic identification
      and subsequent embolization is an effective option. Surgery usually involves
      significant morbidity and is considered a technique of last resort. In this case
      report, we describe the case of middle aged female who developed abdominal
      compartment syndrome (ACS) from a large RSH that had extended into the
      retroperitoneum. The patient underwent abdominal decompression with removal of
      the hematoma and subsequently fared very well. Patients with large RSHs extending
      into the retroperitoneum should undergo constant monitoring of their abdominal
      pressures for early detection and treatment of potentially deadly condition of
      ACS.

PMID- 29181150
TI  - Colo-ovarian fistula.
AB  - Colo-ovarian fistula is a rare entity. The case of a 54-year-old female with a
      colo-ovarian fistula is presented. We describe our experience in managing this
      complication of diverticulitis and propose a workup and treatment plan. Initial
      imaging and diagnostic studies are described. En-bloc resection of the sigmoid
      colon and ovary was performed. A review of the literature is presented.

PMID- 29181149
TI  - A case of pneumatosis intestinalis during neoadjuvant chemotherapy with cisplatin
      and 5-fluorouracil for esophageal cancer?.
AB  - Pneumatosis intestinalis (PI) is a relatively rare disease. A 70-year-old man
      with stage II squamous cell carcinoma of the middle thoracic esophagus was
      administered cisplatin plus 5-fluorouracil (CF) therapy as neoadjuvant
      chemotherapy. On Day 14 of the first course of CF therapy, he complained of acute
      abdominal pain. Computed tomography (CT) revealed PI of the entire colon and a
      small air bubble in the mesentery. A colonoscopy revealed that there was no
      finding suggestive of ischemia. Because there was no sign of peritoneal
      irritation, conservative treatment was selected. On Day 7 after PI diagnosis, CT
      indicated the disappearance of PI. The patient underwent a radical esophagectomy.
      Intraoperative laparoscopic findings showed the serosa of the colon to be intact.
      The patient was discharged without any complications. It is important to take
      into account that CF therapy may cause PI and that PI can be treated
      conservatively.

PMID- 29181151
TI  - Socio-demographic determinants of the severity of locomotor disability among
      adults in Bangladesh: a cross-sectional study, December 2010-February 2011.
AB  - Background: Socio-demographic variables are widely known to have an association
      with the presence of any disability. However, the association between the
      severity of locomotor disability and socio-demographic variables has never been
      investigated in Bangladesh. Methods: A cross sectional survey of adults with
      locomotor disabilities was conducted between December 2010 and February 2011 at
      the Centre for the Rehabilitation of the Paralysed (CRP), Dhaka, Bangladesh.
      During the study period 328 adults with locomotor disabilities met our selection
      criteria, but 316 consented and participated in the study. The 55-item Locomotor
      Disability Scale was used to measure disability. This study investigated the
      socio-demographic determinants of the severity of locomotor disability: age,
      gender, marital status, educational attainment, occupation, income status, type
      of house, living in own/rented house, household monthly income, household
      population and area of residence. Results: Participants' age was positively
      associated with the severity of their locomotor disability (beta = 0.01; 95% CI:
      0.004 to 0.02), adjusting for diagnosis and other socio-demographic variables
      studied. Individuals who had an income experienced 0.35 (95% CI: -0.63 to -0.07)
      points decrease in the severity of disability than those did not have an income,
      adjusting for diagnosis and rest of the socio-demographic variables studied. In
      comparison to the unemployed individuals, students, homemakers, and individuals
      in elementary occupation respectively experienced 0.75 (95% CI: -1.08 to -0.43),
      0.51 (95% CI: -0.82 to -0.19) and 0.37 (95% CI: -0.66 to -0.08) points decrease
      in the severity of locomotor disability, adjusting for diagnosis and rest of the
      socio-demographic variables studied. Conclusions: The severity of locomotor
      disability has an association with individuals' age, income status and occupation
      of the adults with such disability in Bangladesh. No such association was evident
      with other socioeconomic position and demographic variables. This finding
      suggests that people with locomotor disabilities in Bangladesh experience similar
      disabling built and attitudinal environments irrespective of their socioeconomic
      positions and demographic characteristics. Further community-based studies are
      needed to confirm such conclusions.

PMID- 29181152
TI  - Impact of assay temperature on antibody binding characteristics in living cells:
      A case study.
AB  - Kinetic and thermodynamic studies of ligand-receptor interactions are essential
      for increasing the understanding of receptor activation mechanisms and drug
      behavior. The characterization of molecular interactions on living cells in real
      time goes beyond most current binding assays, and provides valuable information
      about the dynamics and underlying mechanism of the molecules in a living system.
      The effect of temperature on interactions in cell-based assays is, however,
      rarely discussed. In the present study, the effect of temperature on binding of
      monoclonal antibodies, cetuximab and pertuzumab to specific receptors on living
      cancer cells was evaluated, and the affinity and kinetics of the interactions
      were estimated at selected key temperatures. Changes in the behavior of the
      interactions, particularly in the on- and off-rates were observed, leading to
      greatly extended time to reach the equilibrium at 21 degrees C compared with at
      37 degrees C. However, the observed changes in kinetic characteristics were less
      than a factor of 10. It was concluded that it is possible to conduct real-time
      measurements with living cells at different temperatures, and demonstrated that
      influences of the ambient temperature on the interaction behavior are likely to
      be less than one order of magnitude.

PMID- 29181153
TI  - Efficacy of alogliptin combined with motor imagery under hyperbaric oxygen in
      diabetic nephropathy with silent cerebral infarction.
AB  - In the present study, we evaluated the curative effect of dipeptidyl peptidase-IV
      (DPP-IV) inhibitor alogliptin combined with motor imagery under hyperbaric oxygen
      in diabetic nephropathy (DN) with silent cerebral infarction (SCI). Two-hundred
      newly diagnosed DN patients with and without SCI were included. The SCI patients
      were divided into two treatment groups: Alogliptin (A group, n=50) and alogliptin
      combined with motor imagery under hyperbaric oxygen (B group, n=50). The degrees
      of neurocognitive dysfunction were evaluated at baseline and after 6 months of
      treatment. Thromboelastograms (TEGs) mapping were conducted. Serum glycoprotein
      VI (GPVI) mRNA expression and urine 11-DH-TXB2 levels were determined. Compared
      to group A patients, the severity of neurofunctional defects, GPVI mRNA
      expression and 11-DH-TXB2 levels were significantly lower in group B (P<0.05),
      while comprehensive, MoCA scores were higher in group B. The MoCA subscores of
      visuospatial/executive function, attention and concentration were significantly
      higher compared to group A (P<0.05). The sub-scores of computation, abstract
      thinking, language competence, memory and orientation were also higher in group B
      but the differences were not significant (P>0.05). TEG indexes were improved in
      both groups after treatment as manifested by increased R and K values, but there
      was significant improvement in group B. Intra-group comparisons revealed a time
      dependent effect of treatment. In conclusion, the treatment of alogliptin
      combined with motor imagery under hyperbaric oxygen can better promote
      thrombolysis absorption, restore brain damage and improve neurocognitive function
      in DN with silent cerebral infarction.

PMID- 29181154
TI  - Hexane fraction of Pluchea indica root extract inhibits proliferation and induces
      autophagy in human glioblastoma cells.
AB  - Pluchea indica (L.) Less. is a perennial plant known for its versatile uses in
      traditional medicine. Previous findings have shown that the extracts of Pluchea
      indica possess significant anti-inflammatory, anti-ulcer and anti-tuberculosis
      activity. The aim of this study was to demonstrate the anticancer activity of the
      hexane fraction of P. indica root extract (H-PIRE) in human glioblastoma cells
      using flow cytometric and western blot analysis. The results shoewd that, H-PIRE
      suppressed the growth of glioblastoma cells in a dose-dependent manner. H-PIRE
      treatment markedly decreased the population of cells in S and G2/M phases. The
      significant upregulation of acidic vesicular organelle (AVO) was detected during
      H-PIRE treatment. The expression levels of microtubule-associated light chain 3
      II (LC3-II) protein, phosphorylated JNK and phosphorylated p38 were significantly
      increased, confirming the occurrence of autophagy during the process. Finally,
      the combination treatment of H-PIRE and LY294002, a pan PI3K inhibitor, further
      decreased cell viability, suggesting an additive anticancer effect. Taken
      together, our results suggest that H-PIRE suppresses the proliferation of
      glioblastoma cells by inducing cell cycle arrest and autophagy.

PMID- 29181155
TI  - Comparison of the effect of the aerobic glycolysis inhibitor dichloroacetate and
      of the Krebs cycle inhibitor LW6 on cellular and humoral alloimmunity.
AB  - Cell metabolism is altered during T-cell and B-cell activation and
      differentiation. Clarifying the exact metabolic shifts may lead to the
      development of new immunosuppressive medications. In this study, the effect of
      the aerobic glycolysis inhibitor dichloroacetate (DCA) and of the Krebs cycle
      enzyme malate dehydrogenase 2 (MDH2) inhibitor LW6 on T-cell alloimmune clonal
      expansion and on alloantibody production, was evaluated. T-cell clonal expansion
      was assessed in two-way mixed lymphocyte reaction (MLR). Humoral alloimmunity was
      evaluated by the alloantibody production in one-way MLR. For this purpose, an
      antibody-mediated complement-dependent cytotoxicity assay was developed in which
      the supernatants from one-way MLRs were used against resting peripheral blood
      mononuclear cells (PBMCs) derived from the same individual that contributed the
      stimulator cells for the respective MLR. DCA had a minimum effect on alloimmune T
      cell clonal expansion, whereas it increased humoral immunity significantly. LW6
      decreased both alloimmune T-cell proliferation and alloantibody production. The
      results indicate that MDH2 may be a perfect target for the development of new
      immunosuppressive medications, especially when inhibition of both cellular and
      humoral alloimmunity is desirable.

PMID- 29181156
TI  - Proteomic profile of the lens in a streptozotocin-induced diabetic rat model
      using shotgun proteomics.
AB  - Streptozotocin (STZ)-induced diabetic rats (STZ rats) were used to investigate
      diabetic cataracts. In the current study, a shotgun liquid chromatography
      (LC)/mass spectrometry (MS)-based global proteomic analysis method was used to
      examine the mechanism of lens opacification as a result of hyperglycemia in STZ
      rats. The 6-week old Wistar rats were injected with STZ for 2 days (100
      mg/kg/day, i.p.) and housed for 3 weeks. The plasma glucose levels were
      identified to be significantly higher when compared with the normal rats and
      insulin was not detected in the STZ rats. Furthermore, opacification of the
      cortical epithelium was observed in the lenses of STZ rats. A total of 235
      proteins were identified in the lenses of the STZ rats and 229 in the lenses of
      the normal rats. A label-free semi-quantitative method, based on spectral
      counting, identified 52 proteins that were differentially expressed in the lenses
      of STZ rats compared with normal rats. In particular, superoxide dismutase, which
      is a critical antioxidant enzyme that detoxifies superoxide through redox
      cycling, was downregulated when analyzed by the semi-quantitative method. In
      addition, phosphorylated-p38, which is important in the signaling pathway
      involved in the oxidative stress response, was significantly increased in the
      lenses of STZ rats when compared with normal rats (P<0.05). Thus, the changes in
      protein expression were evaluated in the lenses of STZ rats using a shotgun LC/MS
      based global proteomic analysis approach, and a decrease in antioxidant enzymes
      and an increase in oxidative stress were identified in the lenses of STZ rats.
      Further studies are required to examine the role of these proteins in the onset
      or progression of diabetic cataracts.

PMID- 29181157
TI  - Non-syndromic isolated dominant optic atrophy caused by the p.R468C mutation in
      the AFG3 like matrix AAA peptidase subunit 2 gene.
AB  - Autosomal dominant optic atrophy (DOA) is the most frequent form of hereditary
      optic atrophy, a disease presenting with considerable inter- and intra-familial
      clinical variability. Although a number of mutations in different genes are now
      known to cause DOA, many cases remain undiagnosed. In an attempt to identify the
      underlying genetic defect, whole exome sequencing was performed in a 19-year-old
      male that had been affected by isolated DOA since childhood. The exome sequencing
      revealed a pathogenic mutation (p.R468C, c.1402C>T) in the AFG3 like matrix AAA
      peptidase subunit 2 (AFG3L2) gene, a gene known to be associated with
      spinocerebellar ataxia. The patient did not show any signs other than DOA. Thus,
      the result demonstrates the possibility that mutations in the AFG3L2 gene may be
      a cause of isolated autosomal DOA.

PMID- 29181158
TI  - Serum pepsinogen and gastrin-17 as potential biomarkers for pre-malignant lesions
      in the gastric corpus.
AB  - There is a lack of non-invasive screening modalities to diagnose chronic atrophic
      gastritis (CAG) and intestinal metaplasia (IM). Thus, the aim of the present
      study was to determine the sensitivity and specificity of serum pepsinogen I
      (PGI), PGI:II, the PGI:II ratio and gastrin-17 (G-17) in diagnosing CAG and IM,
      and the correlations between these serum biomarkers and pre-malignant gastric
      lesions. A cross-sectional study of 72 patients (82% of the calculated sample
      size) who underwent oesophageal-gastro-duodenoscopy for dyspepsia was performed
      in the present study. The mean age of the participants was 56.2+/-16.2 years.
      Serum PGI:I, PGI:II, G-17 and Helicobacter pylori antibody levels were measured
      by enzyme-linked immunosorbent assay. Median levels of PGI:I, PGI:II, the PGI:II
      ratio and G-17 for were 129.9 ug/l, 10.3 ug/l, 14.7 and 4.4 pmol/l, respectively.
      Subjects with corpus CAG/IM exhibited a significantly lower PGI:II ratio (7.2)
      compared with the control group (15.7; P<0.001). Histological CAG and IM
      correlated well with the serum PGI:II ratio (r=-0.417; P<0.001). The cut-off
      value of the PGI:II ratio of <=10.0 demonstrated high sensitivity (83.3%),
      specificity (77.9%) and area under the receiver operating characteristic curve of
      0.902 in detecting the two conditions. However, the sensitivity was particularly
      low at a ratio of <=3.0. The serum PGI:II ratio is a sensitive and specific
      marker to diagnose corpus CAG/IM, but at a high cut-off value. This ratio may
      potentially be used as an outpatient, non-invasive biomarker for detecting corpus
      CAG/IM.

PMID- 29181159
TI  - Investigation of the association between the MDM2 T309G polymorphism and gastric
      cancer.
AB  - Murine double minute clone 2 oncoprotein (MDM2) is a key component in the
      regulation of the tumour suppressor p53. The association between the MDM2
      polymorphism and gastric cancer (GC) has been investigated in Turkish population.
      In the present case-control study, the aim was to investigate the association
      between genetic polymorphisms of the MDM2 gene (a major regulator of p53
      function) and primary GC risk in a Turkish population. The polymorphism, T309G
      (rs2279744) in the MDM2 gene was determined in patients with GC (n=65) and in
      healthy control subjects (n=67) using the polymerase chain reaction-restriction
      fragment length polymorphism method. The findings were evaluated using logistic
      regression and chi2 tests. No statistically significant differences were observed
      between the control subjects and patients with GC regarding smoking status. A
      comparison between GC cases and control subjects indicated a statistically
      significant difference for family history of cancer [odds ratio (OR)=0.17; 95%
      confidence interval (CI), 0.05-0.56; chi2=0.19; P=0.01]. A significant difference
      was identified in the GG genotype distribution between GC patients and control
      subjects (OR=4.58; 95% CI, 1.18-17.79; P=0.022). Thus, the results of the present
      study indicate that the MDM2 gene T309G intron (GG) genotype may be an important
      risk factor for GC development in the Turkish population.

PMID- 29181160
TI  - Secondary central nervous system lymphoma surrounding a region injured by
      subarachnoid hemorrhage and subsequent aneurysmal clipping.
AB  - The present case study describes a rare case of secondary central nervous system
      (CNS) lymphoma that infiltrated the dura and leptomeninges around the area
      injured by subarachnoid hemorrhage and subsequent aneurysmal clipping. Invasion
      of the CNS was observed by computed tomography as slurred fissures of the right
      parietal lobe adjacent to the surgery area. Subdural and subarachnoid enhancement
      overlapping the area injured by past surgical procedures was observed by contrast
      enhanced magnetic resonance imaging. Surgical resection revealed B-cell lymphoma
      infiltrating the dura and leptomeninges surrounding the post-hemorrhagic area.
      The patient was subsequently diagnosed with systemic lymphoma and bone marrow
      invasion, and multiple lymph node swelling. To the best of our knowledge, this is
      the first report of malignant lymphoma involving the CNS overlapping a previously
      injured area.

PMID- 29181161
TI  - Effects of hydration combined with Shenfu injection on contrast-induced acute
      kidney injury in acute coronary syndrome patients undergoing percutaneous
      coronary intervention.
AB  - The aim of the present study was to evaluate the efficacy and safety of the
      Shenfu injection (SFI) in the prevention of contrast-induced acute kidney injury
      (CI-AKI) in acute coronary syndrome (ACS) patients undergoing percutaneous
      coronary intervention (PCI). A single-center prospective and randomized
      controlled trial was performed and 148 ACS patients undergoing PCI were divided
      randomly into control (n=74; receiving only 0.9% sodium chloride solution for
      routine hydration) and intervention (n=74; based upon routine hydration and
      receiving SFI) groups. Serum creatinine (Scr), blood urea nitrogen and urinary
      neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at the start,
      and 1 and 2 days after PCI. Among the 148 patients, 14 (9.4%) experienced CI-AKI
      subsequent to the procedure. CI-AKI occurred in 2.7% of the SFI group and 16.2%
      of the control group (P<0.05). The incidence of CI-AKI was lower in the
      intervention group when compared with the control. No serious adverse effects
      were observed in all patients. No differences between the levels of Scr and
      estimated glomerular filtration rate in the two groups were identified. However,
      12 h after PCI, the urinary NGAL level in the control group was significantly
      higher than that in the SFI group (P<0.05). Thus, hydration combined with SFI was
      identified to be more effective than hydration with sodium chloride in the
      prevention of CI-AKI in ACS patients undergoing PCI.

PMID- 29181162
TI  - Assessing predictors for the success of GnRH antagonist protocol in reproductive
      women in IVF/ICSI - in fresh cycles.
AB  - The aim of the present study was to evaluate the factors that affect the success
      rate of gonadotropin-releasing hormone antagonist on in vitro
      fertilization/intracytoplasmic sperm injection cycles. Multivariate analysis was
      performed to assess the factors that influence the outcomes, such as oocytes
      retrieved, and the success of pregnancy. The results showed that E2, P on human
      chorionic gonadotropin (HCG) day and body mass index (BMI) were positively
      correlated with the number of oocytes retrieved (P=0.001, P=0.024, P=0.017,
      respectively). The duration of infertility as well as the luteinizing hormone on
      HCG day were negatively correlated with the number of oocytes (P=0.048, P=0.002,
      respectively). The age of the women and P on HCG day were negatively correlated
      with successful pregnancy (P<0.001, P=0.022). In conclusion, some parameters,
      such as E2, P, and LH on the HCG day, as well as age and BMI, may affect
      treatment outcomes.

PMID- 29181163
TI  - Oxidative stress and prostatic diseases.
AB  - Prostatic diseases are a common health problem among males in Western countries,
      and include chronic prostatic diseases, which have an unclear pathogenesis and
      few treatment options. In vitro and in vivo studies describe oxidative stress as
      a major pathway involved in the occurrence of benign prostatic hyperplasia,
      prostatic cancer and chronic prostatitis. Thus, the oxidative stress cascade is a
      potential target for the treatment of prostatic diseases. This paper presents a
      systematic review of the available data concerning the association between
      oxidative stress and the most common chronic prostatic diseases, and describes
      the available treatment options that act upon this pathway.

PMID- 29181164
TI  - Recent findings on epigenetic gene abnormalities involved in uterine cancer.
AB  - Selective aberrant genetic effects that do not depend on abnormal DNA sequences
      are referred to as epigenetic abnormalities and are involved in carcinogenesis.
      In uterine cancer, various genes involved in apoptosis, cell cycle, DNA repair,
      cell proliferation and cell adhesion are abnormally methylated, resulting in gene
      silencing. Reversal of such epigenetic abnormalities in cancer cells is a
      potential strategy for cancer therapy, and studies on epigenetic abnormalities
      and treatment methods in uterine cancer are in progress. These include the
      evaluation of 5-hydroxymethylcytosine, which is present in cancer tissues at
      lower levels compared with those in normal tissues, as a prognostic marker in
      cervical cancer; combination therapy with 5-azacytidine and cisplatin;
      combination treatment focusing on tumor necrosis factor-related apoptosis
      inducing ligand in cervical cancer; studies focusing on DNA mismatch repair in
      endometrial cancer; and use of a demethylating agent to reactivate tumor
      suppressor genes and inhibit tumor proliferation. Detection of epigenetic changes
      using biomarkers may be used for histological classification, evaluation of
      disease progression and identification of compounds that are able to modulate
      epigenetic changes and may be useful for uterine cancer treatment.

PMID- 29181165
TI  - Primary extraosseous plasmacytoma of the parotid gland: A case report and
      literature review.
AB  - Extraosseous plasmacytoma (EOP) is an uncommon malignant tumour that is
      characterised by the monoclonal proliferation of abnormal plasma cells in soft
      tissue; however, EOP lacks the defining features of multiple myeloma or medullary
      plasmacytoma. Although the majority of EOP lesions occur in the head and neck,
      EOP of the parotid gland is extremely uncommon. The present study aimed to
      explore the clinical features of parotid plasmacytoma, in addition to the
      diagnostic and therapeutic options for its management. Using the Medline
      database, a search was conducted for articles published on the topic of 'parotid
      plasmacytoma' up until the year 2016. A total of 20 cases were evaluated,
      including 19 clinical cases from the literature and 1 new clinical case from our
      hospital. Among the 19 previously published cases, the mean age at the time of
      diagnosis of EOP was 65.1+/-10.9 years (range, 38-78 years). Plasmacytomas were
      located unilaterally in all cases: On the right side in 9 patients (47.4%), on
      the left side in 10 patients (52.6%). Treatment included chemotherapy in 3 cases,
      radiotherapy in 11 cases and surgical removal in 15 cases. The diagnosis of EOP
      is based on the presence of a localised tumour comprising monoclonal plasma
      cells, and EOP is identical to multiple myeloma in this regard; however, EOP, in
      contrast to multiple myeloma, does not exhibit the signs that are indicative of
      disseminated disease, such as additional lesions on skeletal radiological
      examination, plasmacytosis in the bone marrow, and hypercalcaemia, anaemia, or
      renal failure. Thus, EOP must be considered in the differential diagnosis of
      parotid gland lesions in order to avoid confusion with other tumoural diseases.

PMID- 29181166
TI  - Successful and long-term response to trastuzumab plus paclitaxel combination
      therapy in human epidermal growth factor receptor 2-positive extramammary Paget's
      disease: A case report and review of the literature.
AB  - A 58-year-old woman with a histologically confirmed diagnosis of vulvar
      extramammary Paget's disease (EMPD) was referred to our hospital due to locally
      advanced and relapsed EMPD. The patient had undergone surgical resection three
      times for relapsed vulvar EMPD over a period of 12 years, but developed locally
      advanced and unresectable EMPD. As pathological examination indicated that the
      lesion was positive for human epidermal growth factor receptor 2 (HER2) on
      immunohistochemical staining, the patient was treated with trastuzumab plus
      paclitaxel. The primary tumor mass and lymph node metastasis regressed
      successfully with combined trastuzumab and paclitaxel therapy, and the disease
      has been stable for >2 years after the initiation of treatment. These
      observations suggest that HER2 status must be determined in patients with
      advanced and/or metastatic extramammary Paget's disease and therapy with HER2
      inhibitors should be considered as an option for the treatment of HER2-positive
      EMPD.

PMID- 29181167
TI  - Long-term outcomes of laparoscopy vs. open surgery for colorectal cancer in
      elderly patients: A meta-analysis.
AB  - The long-term outcome of laparoscopic surgery for geriatric patients with
      colorectal cancer remains unclear due to decreased functional reserves and
      increased medical comorbidities. A meta-analysis was performed in the present
      study to compare the long-term outcome between laparoscopy and laparotomy.
      Randomized controlled trials and comparative studies regarding laparoscopy vs.
      open surgery for colorectal cancer in elderly patients were searched in Pubmed,
      Embase, and Cochrane library between inception and April 20, 2017. The
      methodological quality of the cohort studies was evaluated using the Newcastle
      Ottawa Scale. The meta-analysis was performed using Stata v12.0 software. Eight
      cohort studies were enrolled in the meta-analysis. Laparoscopic surgery was
      associated with a higher 3-year survival rate compared with open surgery [risk
      ratio (RR), 0.74; 95% confidence interval (CI), 0.61-0.90; P=0.003]. No
      significant difference was identified between laparoscopy and laparotomy
      regarding the 5-year survival rate (RR, 0.93; 95% CI, 0.78-1.11, P=0.424). The
      results of the meta-analysis indicated that the use of laparoscopic surgery on
      geriatric patients with colorectal cancer should be increased due to more
      improved long-term outcomes. All the studies included in the meta-analysis were
      case-control studies with selection bias and other confounding factors. Thus,
      larger sample sizes and multicenter randomized controlled trials are required to
      further validate the use of laparoscopic surgery as the preferred therapeutic
      option for elderly patients with colorectal cancer.

PMID- 29181168
TI  - Schwannoma of the vagina - a common tumor but a rare location: A case report.
AB  - Schwannomas are nerve sheath tumors arising from Schwann cells. These tumors
      usually present as benign, relatively slow-growing, solitary, encapsulated,
      painless masses. Schwannomas rarely occur in the vagina, and have not been fully
      recognized as gynecological tumors. We herein describe the case of a patient who
      presented with a schwannoma occurring in the wall of vagina, with non-specific
      symptoms lasting for ~1 year. The vaginal mass was incidentally detected during a
      sonographic examination and the patient was referred for surgical resection. The
      surgery was uncomplicated and the vaginal tumor was diagnosed as benign
      schwannoma. The immunohistochemical examination revealed positivity for vimentin,
      S-100 and glial fibrillary acidic protein, whereas discovered on GIST-1, CD117,
      CD34, desmin, smooth muscle actin and cytokeratin were negative. Tumors occurring
      in the vagina are common and are of variable histological types, with a wide
      range of pathological characteristics and complications. Schwannoma should be
      considered in the differential diagnosis in patients presenting with atypical
      symptoms from the gynecological tract. Immunohistochemical staining is required
      for confirmation of the diagnosis of schwannoma, and for distinguishing this
      entity from other homologous tumors.

PMID- 29181169
TI  - Retrospective analysis of single-agent nab-paclitaxel in patients with platinum
      resistant non-small cell lung cancer.
AB  - A retrospective study was conducted to investigate the efficacy and toxicity of
      single-agent nab-paclitaxel in 67 patients with platinum-resistant non-small cell
      lung cancer in Kansai Medical University Hospital from August 2013 to December
      2015. Overall, 25% of patients experienced disease progression, 48% exhibited a
      partial response, 27% had stable disease and 0% had a complete response. The
      median progression-free survival (PFS) time was 4.8 months and the median overall
      survival time was 18.2 months. There was no statistically significant difference
      in PFS between patients with non-squamous carcinoma and squamous carcinoma, or
      between second-line use and post-second-line use. The most common severe adverse
      event was neutropenia, followed by interstitial lung disease, infection and
      fatigue. The results revealed that single agent nab-paclitaxel was associated
      with an acceptable level of toxicity and a favorable response. This regimen has
      been developed recently, thus it has not been sufficiently evaluated its toxicity
      and efficacy. Additional studies to evaluate these parameters in non-small cell
      lung cancer are warranted.

PMID- 29181170
TI  - Role of Kruppel-like factor 4 and heat shock protein 27 in cancer of the larynx.
AB  - Late detection and lack of standard treatment strategies in larynx cancer
      patients result in high levels of mortality and poor prognosis. Prognostic
      stratification of larynx cancer patients based on molecular prognostic tumor
      biomarkers may lead to more efficient clinical management. Kruppel-like factor 4
      (KLF4) and Heat Shock Protein 27 (HSP27) have an important role in tumorigenesis
      and are considered promising candidate biomarkers for various types of cancer.
      However, their role in larynx carcinoma remains to be elucidated. The present
      study aimed to determine KLF4 and HSP27 expression profiles in laryngeal tumors.
      The protein and mRNA expression levels of KLF4 and HSP27 were evaluated by
      immunohistochemical and reverse transcription-polymerase chain reaction analyses
      in 44 larynx carcinoma samples and 21 normal tissue samples, and then correlated
      with clinical characteristics. A differential expression of KLF4 and HSP27 was
      observed between normal and tumor tissues. The protein and mRNA expression levels
      of KLF4 were significantly decreased in larynx squamous cell carcinoma (LSCC)
      compared with normal tissue, whereas HSP27 was significantly overexpressed in
      tumor tissues compared with normal tissues, at the protein and mRNA levels. KLF4
      expression decreased gradually with tumor progression whereas HSP27 expression
      increased. A significant difference was observed between stages I and IV. KLF4
      and HSP27 exhibit opposite functions and roles in the carcinogenic process of
      LSCC. Their role in laryngeal cancer initiation and progression emphasizes their
      use as potential future targets for prognosis and treatment. KLF4 and HSP27
      expression levels may act as potential biomarkers in patients with cancer of the
      larynx.

PMID- 29181171
TI  - Subserous invasion of VEGF-C-producing cancer cells is a possible risk factor for
      ileal ulceration in the non-metastatic mucosal layer during bevacizumab-combined
      chemotherapy for recurrent ovarian cancer: A case report.
AB  - A 65-year-old woman received chemotherapy using taxane and carboplatin prior and
      following optimal debulking surgery for ovarian cancer stage IV. Five months
      later, intra-abdominal recurrence was diagnosed, and second-line chemotherapy
      using nogitecan and bevacizumab was administered. After five courses, the patient
      presented with a symptom of subileus and subsequent intestinal perforation
      occurred. An emergent surgery revealed two perforation sites and longitudinally
      extended ulcerative lesions in the ileum. Pathologically, although metastatic
      sites were not observed in the submucus layer just beneath the ulcers, there were
      a number of vascular endothelial growth factor (VEGF)-C-positive cancer cell
      invasion sites along with marked edema and an increase of the lymphatic
      endothelial cell marker 'podoplanin'-positive cells in subserous regions. Since
      bevacizumab is able to inhibit VEGF-A, but not VEGF-C, and induce compensatory
      increase in VEGF-C production, these findings suggest that the local disturbance
      of lymphatic circulation in the subserous regions by VEGF-C-producing cancer
      cells is a possible risk factor for the development of intestinal ulceration and
      perforation during bevacizumab therapy.

PMID- 29181172
TI  - Trigeminal neurofibroma in the infratemporal fossa arising from the inferior
      alveolar nerve: A case report.
AB  - Solitary neurofibromas arising from cranial nerves are rare, and those arising
      from the peripheral divisions of the trigeminal nerve are even rarer. Although
      infratemporal fossa (ITF) masses are challenging to remove, certain approaches
      are considered feasible for this region. The present study reports a rare case of
      an ITF neurofibroma arising from the inferior alveolar nerve. The 27-year-old
      male patient presented with numbness of the right jaw. A radiological examination
      revealed a large mass occupying the ITF, from the mandible to the foramen ovale,
      originating from the inferior alveolar nerve in the mandible. The tumor was
      successfully excised via a transtemporal approach followed by a transoral
      retromolar approach. A histological examination confirmed the diagnosis of
      neurofibroma. The present case demonstrates that a combination of the
      transtemporal and transoral-retromolar approaches may provide wide access to the
      ITF region.

PMID- 29181173
TI  - Transverse colon schwannoma treated by endoscopic mucosal resection: A case
      report.
AB  - Gastrointestinal (GI) schwannoma is one of the rarest tumors of the GI tract. We
      herein describe the case of a 70-year-old female patient who presented for
      surveillance colonoscopy. The examination detected a 1-cm polyp that was removed
      by snare cautery polypectomy. Immune and histochemical staining revealed spindle
      cells that were positive for S-100 and vimentin, but negative for CD34 and smooth
      muscle actin, consistent with GI schwannoma. This case is noteworthy as GI
      schwannomas usually present in the stomach, making the finding of a colonic
      schwannoma of clinical interest. Furthermore, the present case was treated by
      removing the tumor endoscopically, in contrast to more invasive methods.

PMID- 29181174
TI  - Rapid occurrence of left ventricular thrombus associated with platinum-based
      chemotherapy plus cetuximab for the treatment of metastatic squamous cell
      carcinoma of the head and neck: A case report.
AB  - Platinum-based chemotherapy plus cetuximab represents the first-line treatment
      for recurrent or metastatic squamous cell carcinoma of the head and neck. The
      most common adverse events associated with cetuximab are infusion reactions and
      skin reactions, and a risk of venous thromboembolic events has also recently been
      reported in association with cetuximab. It is well known that thrombosis is a
      common complication of malignancy, and represents the second most frequent cause
      of mortality in cancer patients. The present study reports the case of a 79-year
      old man who presented with lung and liver metastases from tongue squamous cell
      carcinoma, for which platinum-based chemotherapy plus cetuximab was administered.
      After 1 cycle, the patient showed rapid growth of a left ventricular (LV)
      thrombus, despite ongoing antiplatelet therapy for an old myocardial infarction.
      Anticoagulant therapy was administered to treat the LV thrombus, which resolved
      within 1 week. To the best of our knowledge, this represents the first reported
      case of rapidly occurring LV thrombus associated with platinum-based chemotherapy
      plus cetuximab. Platinum-based chemotherapy plus cetuximab may be associated with
      a higher risk of embolic thrombus.

PMID- 29181175
TI  - Peripheral blood neutrophil count as a prognostic factor for patients with
      hepatocellular carcinoma treated with sorafenib.
AB  - Sorafenib is currently the only efficient molecular targeted therapy for
      hepatocellular carcinoma (HCC), although its effect is relatively moderate and
      variable between individuals. The present study aimed to evaluate the
      significance of peripheral blood neutrophils in the prognosis of HCC patients
      treated with sorafenib. A total of 464 patients with HCC were treated with
      sorafenib at Zhongshan Hospital (Shanghai, China) between January 1st, 2008 and
      December 31st, 2012, among which 120 patients were enrolled in the study. The
      optimal cutoff point for low vs. high neutrophil count (3.65*109) was obtained
      from a receiver operating characteristic curve. Overall survival (OS) was
      compared between the patients with low and high peripheral neutrophil counts.
      Univariate and multivariate analyses were used to explore the prognostic factors
      associated with OS in the patients treated with sorafenib. A nomogram model was
      also performed to predict the OS times of these patients. The median OS time was
      9.0 months (95% confidence interval, 5.9-12.1 months) in the whole group of
      patients, with 1-, 2- and 3-year OS rates of 36, 24 and 16%, respectively. Using
      a cutoff level of 3.65*109 neutrophils/l, the median OS time was longer in the
      group of patients with a low peripheral neutrophil count than in those with a
      high peripheral neutrophil count (11.5 vs. 5.0 months, respectively; P<0.001).
      The multivariate analysis showed that peripheral neutrophil count, alpha
      fetoprotein level and tumor size were independent prognostic factors for OS. In
      addition, using the nomogram model for the prediction of OS, the Harrell's c
      index was 0.79. Therefore, it was concluded that a lower peripheral blood
      neutrophil count was associated with a better prognosis following treatment with
      sorafenib therapy.

PMID- 29181176
TI  - Chemoprevention using folic acid for dysplastic lesions of the larynx.
AB  - Folate deficiency may be directly associated with carcinogenesis. Folate
      supplementation may reduce the risk of progression in a mucosa that is already
      genetically altered. The aim of the present study was to determine the role of
      folic acid in the treatment of mild and moderate laryngeal dysplasia recurring
      after surgery. The data obtained by laryngoscopy, measurement of serum folate
      levels and functional vocal assessment with the GIRBAS scale and VHI
      questionnaire were compared in patients who had received folic acid with a
      homogeneous group of patients with dysplasia who had not undergone any therapy. A
      total of 24 patients suffering from recurrence of mild or moderate laryngeal
      dysplasia (n=12, group A) were treated with 400 mg folic acid per os, once daily
      for 6 months. The patients in group B (n=12) received no treatment and were used
      as the control group. In group A, 7 (58%) patients exhibited a complete response,
      with clinically evident regression of leukoplakia, 3 (25%) displayed a partial
      decrease in the lesions with reduced volume of the area involved, whereas 2
      patients exhibited no change. As regards patients in control group B, 8 (67%)
      exhibited no change, in 1 case there was a spontaneous regression, and in 3 (25%)
      there was disease progression with suspected malignant transformation, leading to
      repeat surgery. Therefore, folate deficiency may be considered to be a factor
      predisposing to precancerous lesions, and dietary folate supplementation may
      prevent and reduce the emergence of cancer.

PMID- 29181177
TI  - Recurrent maxillary sinus cancer with only adrenal metastasis.
AB  - Maxillary sinus cancer is rare, and often presents as a locally advanced disease.
      Recurrence commonly occurs locoregionally, while fewer patients present with
      distant metastasis; the most common sites involved are the lung and bone. This
      report discusses the case of a 64-year-old male who presented with a mass in the
      left submandibular area. Biopsy was performed and histological analysis
      identified a poorly differentiated squamous cell carcinoma. After staging work
      up, it was concluded the patient had a maxillary sinus squamous cell carcinoma at
      clinical stage IVA. The patient received a left partial maxillectomy and left
      radical neck dissection followed by postoperative chemoradiotherapy. After three
      months of CRT, the patient developed a left adrenal gland metastasis without
      locoregional failure. The patient subsequently received a laparoscopic left
      adrenalectomy and the results of histological analysis revealed a poorly
      differentiated squamous cell carcinoma. Within one month of surgery, the patient
      had developed multiple metastases at the left adrenalectomy site and succumbed to
      the disease four months later.

PMID- 29181178
TI  - Development of lymphoma from the donor of haploidentical stem cell
      transplantation: A case report.
AB  - Post-transplantation lymphoproliferative disease (PTLD) is a serious complication
      following hematopoietic stem cell transplantation (HSCT). The majority of the
      cases develop during the first year after the transplantation and are associated
      with reactivation of the Epstein-Barr virus (EBV); the EBV-induced
      lymphoproliferation usually includes donor-derived B cells. We herein describe
      the case of a 28-year-old female patient who developed EBV-negative PTLD, namely
      diffuse large B-cell lymphoma (DLBCL), 6 months after receiving a haploidentical
      HSCT from her father. Chimerism analysis performed with XY fluorescence in situ
      hybridization revealed a B-cell PTLD originating from the donor. Unfortunately,
      the donor also developed DLBCL 380 days after donating progenitor cells, although
      he was hematologically normal at the time of donation. The present case
      demonstrated that disease transmitted from the donor may be a possible cause of
      PTLD.

PMID- 29181179
TI  - Efficacy of bendamustine on thrombocytopenia and hemolytic anemia secondary to
      CD5-positive B-cell lymphoma with massive splenomegaly in a patient with
      rheumatoid arthritis.
AB  - Chemotherapy for lymphoma may be avoided in the presence of coincident cytopenia.
      In case of immune cytopenia secondary to lymphoma, treatment of cytopenia is the
      same for primary cases, however, chemotherapy for lymphoma may be effective at
      the cost of severe hematological toxicity. The present study reports a complex
      case of thrombocytopenia and direct antiglobulin test-negative hemolytic anemia,
      thus mimicking Evans syndrome, secondary to cluster of differentiation 5-positive
      B-cell lymphoma with massive splenomegaly, in a patient suffering from rheumatoid
      arthritis for two decades. Treatment with prednisolone, high-dose dexamethasone,
      eltrombopag and rituximab for cytopenia were not effective. Chemotherapy with
      bendamustine subsequently resolved the cytopenia, additionally resulting in a
      complete remission of lymphoma. Thus, bendamustine may have a role in the
      management of lymphoma complicated with severe cytopenia.

PMID- 29181180
TI  - Comprehensive treatment of unresectable cardiac angiosarcoma: A case report and
      review of literature.
AB  - Cardiac angiosarcoma is a rare but lethal tumor that is difficult to diagnose and
      treat, due to its rapid local relapse and high incidence of systemic metastasis.
      The prognosis of cardiac angiosarcoma is dismal, with a mean life expectancy of
      only a few months. We herein report a case of unresectable angiosarcoma arising
      from the right atrium. The patient received first-line chemotherapy with weekly
      paclitaxel, and second-line therapy with vinorelbine and bevacizumab upon disease
      progression. The progression-free survival was 6 months and the overall survival
      was 7 months. The patient eventually succumbed to respiratory failure. A study of
      the present case and a review of the relevant literature suggest that treatment
      decisions for unresectable locally advanced or metastatic cardiac angiosarcoma
      are difficult, as the published literature on this disease mainly consists of
      case reports without sufficient data. Therefore, further clinical trials specific
      to the treatment of unresectable cardiac angiosarcoma are warranted.

PMID- 29181181
TI  - Adjuvant chemotherapy for patients with ypT0-2N0-category after neoadjuvant
      chemoradiotherapy for rectal cancer.
AB  - Locally advanced rectal cancer patients with ypT0-2N0 have good prognosis and may
      not require as many cycles of adjuvant chemotherapy as patients with a poor (ypT3
      4 or N+) response. The aim of the present study was to evaluate the three-year
      disease-free and overall survival between patients with ypT0-2N0 rectal
      adenocarcinoma who received 0-3 cycles of 5-fluorouracil-based adjuvant
      chemotherapy and those who received >3 cycles. A total of 106 patients with
      locally advanced rectal cancer, classified as ypT0-2N0 after surgery at the Fudan
      University Shanghai Cancer Center (Shanghai, China) between 2006 and 2012, were
      identified. The patients were divided into two groups depending on the number of
      cycles of adjuvant chemotherapy: Group 1 received 0-3 cycles (n=32) and group 2
      received >=4 cycles of adjuvant chemotherapy (n=74). The three-year disease-free
      survival and overall survival rates were 86.8 and 93.1% for group 1 (P=0.633),
      and 88.5 and 96.8% for group 2 (P=0.381). No statistically significant difference
      was observed between the two groups, suggesting that patients with ypT0-2N0
      status may not require more than three cycles of post-operative chemotherapy.
      Further evaluation in prospective studies is urgently recommended.

PMID- 29181182
TI  - Solitary nodule of angiolymphoid hyperplasia with eosinophilia of the back
      masquerading as pyogenic granuloma.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare chronic inflammatory
      disorder of unknown etiology that most commonly presents as painless
      lymphadenopathy or subcutaneous masses in the head and neck region. The
      pathogenesis of the disease is not yet clear. The differential diagnosis is
      determined using characteristic histological features, such as significant
      vascular proliferation, lymphocytes and eosinophil inflammation in the dermis.
      Here is presented the case of a patient with a solitary nodule of ALHE
      masquerading as pyogenic granuloma (PG). A 47 year-old male patient was admitted
      with an isolated lump on the right side of the back, which had been present for
      ~6 months; the nodule appeared to have characteristics of PG and was ~1.8*1.0 cm2
      in diameter. To the best of our knowledge, this is the first case report
      regarding ALHE arising in the back. The present report discusses the
      manifestation, histopathological features and treatment of the case.

PMID- 29181183
TI  - Internal fixation combined with bone grafting for large intraosseous calcaneal
      lipoma: A case report.
AB  - Intraosseous lipoma is a rare benign bone tumor that has been reported to occur
      in the calcaneus and long bones. The etiology of intraosseous lipoma is unknown,
      although several theories have been proposed. The majority of the cases of
      intraosseous calcaneal lipoma reported in the literature were localized in the
      anterior portion of the calcaneus and were treated by curettage and bone
      grafting. However, for larger lipomas, no specific treatment protocol has been
      developed to date. We herein present a rare case involving a large intraosseous
      lipoma of the calcaneus in a 36-year-old man following hindfoot trauma. The
      lesion was treated by decortication followed by bone grafting and internal
      fixation, a surgical approach that, to the best of our knowledge, has not been
      previously described in the literature.

PMID- 29181184
TI  - Claudin-1 expression in cervical cancer.
AB  - Claudin-1 is a tight junction protein that has been demonstrated to be involved
      in tumorigenesis and tumor progression in various types of solid tumors. In the
      present study, the protein expression of claudin-1 in squamous cervical cancer
      tissues obtained from 106 patients was analyzed by immunohistochemistry. In
      addition, the grade of claudin-1 expression was analyzed for associations with
      certain clinicopathological parameters. A significant overexpression of claudin-1
      was detected in the tumor cells, when compared with that in the peritumoral
      stroma. There was no significant association between claudin-1 expression and
      FIGO stage, tumor size, grading or the appearance of distant metastases. Cervical
      cancer patients scoring positive for claudin-1 protein expression tended to
      exhibit more lymph node metastasis (28.3%), compared with claudin-1-negative
      patients (7.1%). Regarding overall survival, the results of the present study
      suggest a better prognosis for claudin-1-negative patients. In order to elucidate
      whether claudin-1 overexpression has a significant prognostic impact on squamous
      cervical cancer, further studies are required.

PMID- 29181185
TI  - Prognostic factors in patients with skeletal-related events at non-small-cell
      lung cancer diagnosis.
AB  - The aim of the present study was to detect prognostic factors in patients with
      skeletal-related events (SREs) and bone metastasis at the time of non-small-cell
      lung cancer (NSCLC) diagnosis. A total of 85 NSCLC patients were retrospectively
      enrolled, 47 (55.2%) of whom presented with SREs at the time of NSCLC diagnosis.
      Multivariate logistic regression analysis identified squamous cell carcinoma as a
      risk factor for SRE. Kaplan-Meier analysis demonstrated that there was no
      difference in the overall survival between the SRE and no SRE groups. Cox hazard
      model revealed that a higher Eastern Cooperative Oncology Group (ECOG)
      performance status (PS) score was a risk factor for poor prognosis, while surgery
      for bone metastasis and molecular-targeted therapy were factors for better
      prognosis in patients with SREs at the time of NSCLC diagnosis. Multivariate
      analysis revealed that a higher ECOG PS score and metastasis to the adrenal gland
      were risk factors for poor prognosis, while surgery for bone metastasis and
      molecular-targeted therapy were factors for better prognosis. Thus, while
      surgical treatment and molecular-targeted therapy appear to improve the prognosis
      of patients with bone metastasis at the time of NSCLC diagnosis, those with a
      higher ECOG PS score and adrenal metastasis may benefit more from radiotherapy or
      supportive care.

PMID- 29181186
TI  - Enhanced antitumor effects and improved immune status of dendritic cell and
      cytokine-induced killer cell infusion in advanced cancer patients.
AB  - Little progress has been made in the treatment of advanced cancer. Dendritic
      cells (DCs) plus cytokine-induced killer (CIK) cells have exhibited antitumor
      effects. Thus, the aim of the present study was to evaluate the clinical efficacy
      of DC-CIK cell treatment in patients with advanced cancer. A paired study
      including 57 patients treated with DC-CIK cells (DC-CIK group) and 33 patients
      treated with best supportive care alone (BSC group) was performed. The patients
      in the DC-CIK group were matched to those in the control group in terms of sex,
      age, tumor type and clinical stage. T-cell subsets were detected and overall
      survival (OS) was compared between the two groups. The results demonstrated that
      CD4+/CD25+ and CD8+/CD28- subsets significantly decreased following DC-CIK
      immunotherapy (P<0.05). The CD3+, CD3+/CD8+, CD8+/CD28+ and CD3+/CD56+ T-cell
      subsets were significantly increased in the DC-CIK group compared with the BSC
      group, while the CD8+/CD28- subset was significantly decreased. Univariate
      analysis demonstrated that a lower CD8+/CD28- and a higher CD8+/CD28+ ratio were
      associated with prolonged OS in advanced cancer patients. In addition, DC-CIK
      treatment administration, age (>60 vs. <60 years), clinical stage and the
      frequency of CIK treatment significantly affected the OS of patients in the DC
      CIK group. A CD8+/CD28- ratio of <21.12 was found to decrease the hazard ratio
      (HR) of OS to 0.50 [95% confidence interval (CI): 0.29-0.87] and a CD8+/CD28+
      ratio >9.04 was found to decrease the HR of OS to 0.45 (95% CI: 0.21-0.98). No
      serious side effects were observed in the DC-CIK group. Taken together, these
      data indicate that DC-CIK infusions were able to change the ratios of the T-cell
      subsets, which increased the T helper cell and cytotoxic T lymphocyte subsets,
      while it decreased regulatory T lymphocyte subsets. Thus, this method of
      immunotherapy was found to improve the imbalance in the immune system and prolong
      the OS in patients with advanced cancer.

PMID- 29181187
TI  - Primary duodenal follicular lymphoma with late disseminated nodal relapse
      responsive to rituximab monotherapy: A case report.
AB  - Gastrointestinal follicular lymphoma is a rare malignancy accounting for only 1
      3.6% of primary non-Hodgkin lymphomas of the gastrointestinal tract and it is a
      relatively new clinical entity that was recently classified as a distinct variant
      of systemic follicular lymphoma. Therefore, data regarding long-term outcome are
      currently lacking. In addition, a consensus on the management of this disease has
      not been established and treatment strategies are derived from systemic
      follicular lymphoma. We herein report the case of a 51-year-old female patient
      diagnosed with duodenal follicular lymphoma who had nodal relapse nearly 5 years
      after complete remission. The patient was successfully treated with a 4-week
      course of rituximab during the initial diagnosis and relapse. To the best of our
      knowledge, this is the first case report to demonstrate the efficacy of a 4-week
      course of rituximab during both the initial diagnosis and nodal relapse. The aim
      of this report was to add to the limited available data on the treatment of
      gastrointestinal follicular lymphoma.

PMID- 29181188
TI  - Intra-articular osteochondroma of the posteroinferior femoral neck associated
      with hip joint osteochondromatosis: A case report.
AB  - Osteochondromas are usually extra-articular lesions originating from the
      metaphysis of long bones. Intra-articular osteochondromas may also occur, causing
      pain and discomfort and restricting the range of motion. Osteochondromas of the
      femoral neck are intra-articular lesions that are difficult to access for
      surgical resection, particularly when located posteriorly. We herein present a
      rare case of an intra-articular osteochondroma involving the posteroinferior
      aspect of the femoral neck associated with secondary synovial osteochondromatosis
      (SOC) of the hip joint in a 25-year-old woman. Determining the optimal treatment
      was difficult due to the high risk of avascular necrosis (AVN) following surgical
      excision. The patient was successfully treated with arthroscopic surgery and she
      remained in good condition at 2 years postoperatively, with a full range of
      motion of the hip joint, and without signs of limping, recurrence of the SOC, or
      AVN of the femoral head.

PMID- 29181189
TI  - Expression and clinical significance of androgen receptor in bladder cancer: A
      meta-analysis.
AB  - Emerging evidence has demonstrated that androgen receptor (AR) is a promising
      therapeutic target for bladder cancer. However, the relationship between AR
      expression and its clinical significance remains controversial. The present in
      depth meta-analysis aimed to investigate the correlation between AR expression
      and clinicopathological features, as well as prognostic value in bladder cancer.
      A systematic search was performed from PubMed, Web of Knowledge, Embase and the
      Cochrane Central Search Library by January 2017. The correlation between AR
      expression and tumor stage, tumor grade, recurrence free survival and progression
      free survival for patients with bladder cancer was evaluated. A total of 12
      relevant studies with 1,652 patient samples were included. AR expression
      positively correlated with low tumor grade [odds ratio (OR), 1.95; 95% confidence
      interval (CI), 1.36-2.81], low tumor stage (OR, 2.06; 95% CI, 1.02-4.16) and low
      recurrence rate [hazard ratio (HR), 0.48; 95% CI, 0.31-0.75] in Caucasian
      patients. While, its expression had no significant impact on cancer
      susceptibility (OR, 1.62; 95% CI, 0.19-13.72; P=0.44) and progression-free
      survival (HR, 1.20; 95% CI, 0.86-1.66; P=0.77). The present meta-analysis
      indicated that AR expression correlates with tumor grade, clinical stage and
      recurrence rates in the specified population and classification system. Further
      studies are required to determine the precise role of AR in bladder cancer.

PMID- 29181190
TI  - External quality assessment for EGFR mutations in Italy: improvements in
      performances over the time.
AB  - External quality assessment (EQA) schemes are essential procedures to assess the
      quality level of laboratories performing molecular testing of the epidermal
      growth factor receptor (EGFR) gene in non-small cell lung cancer. The Italian
      Association of Medical Oncology (AIOM) and the Italian Society of Pathology
      (SIAPEC-IAP) organise EGFR EQA programmes to ensure that the Italian laboratories
      achieve the quality standard levels required. Comparing the 2011, 2013 and 2015
      EGFR EQA schemes, it was possible to observe improvements in the methodologies
      used and the outcomes. The use of direct sequencing was reduced from 78.7% in
      2011 to only 14.1% in 2015, whereas the use of pyrosequencing and real-time PCR
      increased. The number of rounds in which centres using direct sequencing failed
      was significantly higher than the number of rounds that failed using other
      methods, both when analysing each single scheme and when combining the three EQAs
      together. In 2011 and 2013, about 29% of the participants failed the first phase
      of the programmes, compared with the 13% of centres failing in 2015, suggesting
      that the switch to more sensitive and robust methods could allow to increase the
      percentage of good performers. Although the molecular analyses are performed with
      good quality in Italy, the continuous education carried out by AIOM and SIAPEC
      IAP remains a fundamental tool to maintain this quality level.

PMID- 29181191
TI  - Anti-PD-1/anti-PD-L1 immunotherapy versus docetaxel for previously treated
      advanced non-small cell lung cancer: a systematic review and meta-analysis of
      randomised clinical trials.
AB  - Background: To compare the efficacy and toxicity of anti-programmed cell death
      receptor 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) versus
      docetaxel in previously treated patients with advanced non-small cell lung cancer
      (NSCLC). Materials and methods: Phase III randomised clinical trials (RCTs) were
      identified after systematic review of databases and conference proceedings. A
      random-effect model was used to determine the pooled HR for overall survival
      (OS), progression-free survival (PFS) and duration of response. The pooled OR for
      overall response and treatment-related side effects were calculated using the
      inverse-variance method. Heterogeneity was measured using the tau2 and I2
      statistics. Results: After the systematic review, we included four phase III RCTs
      (n=2737) in this meta-analysis. The use of anti-PD-1/anti-PD-L1 agents
      (atezolizumab, nivolumab and pembrolizumab) was associated with better OS in
      comparison with docetaxel alone (HR: 0.69; 95% CI 0.63 to 0.75; p<0.00001).
      Similarly, the PFS and duration of response was significantly longer for patients
      receiving immunotherapy (HR: 0.85; 95% CI 0.75 to 0.96; p=0.007 and HR:0.32; 95%
      CI 0.24 to 0.43; p<0.00001, respectively) versus single agent chemotherapy. The
      overall response rate was also higher for patients who received any anti-PD
      1/anti-PD-L1 therapy in comparison with docetaxel (OR: 1.77; 95% CI 1.26 to 2.50;
      p=0.001). Regarding treatment-related side effects grade 3 or higher, patients
      who received immunotherapy experienced less events than patients allocated to
      docetaxel (OR: 0.19; 95% CI 0.12 to 0.30; p<0.00001). Conclusion: The use of anti
      PD-1/anti-PD-L1 therapy in patients with progressive advanced NSCLC is
      significantly better than the use of docetaxel in terms of OS, PFS, duration of
      response and overall response rate.

PMID- 29181192
TI  - Selecting PCR for the Diagnosis of Intestinal Parasitosis: Choice of Targets,
      Evaluation of In-House Assays, and Comparison with Commercial Kits.
AB  - Microscopy of stool samples is a labour-intensive and inaccurate technique for
      detection of intestinal parasites causing diarrhoea and replacement by PCR is
      attractive. Almost all cases of diarrhoea induced by parasites over a nine-year
      period in our laboratory were due to Giardia lamblia, Cryptosporidium species, or
      Entamoeba histolytica detected by microscopy. We evaluated and selected in-house
      singleplex real-time PCR (RT-PCR) assays for these pathogens in 99 stool samples
      from patients suspected of having intestinal parasitosis tested by microscopy.
      The strategy included a genus-specific PCR assay for C. parvum and C. hominis,
      with subsequent identification by a PCR that distinguishes between the two
      species. G. lamblia was detected in five and C. parvum in one out of 68
      microscopy-negative samples. The performance of the in-house RT-PCR assays was
      compared to three commercially available multiplex test (MT-PCR) kit systems in
      81 stool samples, collected in 28 microscopy-positive and 27 microscopy-negative
      samples from individuals suspected of intestinal parasitosis and in 26 samples
      from individuals without suspicion of parasitic infection. The in-house assays
      detected parasites in more samples from patients suspected of having parasitosis
      than did any of the kits. We conclude that commercial kits are targeting relevant
      parasites, but their performance may vary.

PMID- 29181195
TI  - Survey of Extent of Translation of Oral Healthcare Guidelines for ICU Patients
      into Clinical Practice by Nursing Staff.
AB  - Nosocomial infections in critically ill/ventilated patients result from bacterial
      load in oropharyngeal regions. Oral decontamination serves as the easiest
      effective means of controlling infections. Knowledge, attitude, and practices
      followed by healthcare personnel in intensive care settings need to be assessed
      to implement concrete measures in health-care. Survey questionnaire was
      constructed and implemented following its validation on seventy nursing and
      paramedical staff working in government and private intensive care units
      throughout Lucknow city. 21-item questionnaire consisted of three parts of seven
      questions each. 78% of respondents had knowledge regarding oral care and its
      importance in critical settings but 44% of respondents considered it to be
      unpleasant task. 36% of respondents claimed to have provided oral care to all
      patients in ICU. Uniform guidelines for translation of oral healthcare in ICU
      settings are not being implemented. Previous studies in literature from various
      geographic diverse regions also point out to similar lacunae. Based on present
      survey, most respondents were aware of importance of oral care with protocols
      covered in academic curriculum. Attitude towards oral care is positive but
      respondents feel a need for specialised training. Practice for oral care is not
      sufficient and needs improvement and proper implementation.

PMID- 29181196
TI  - 99mTc-Sestamibi/123I Subtraction SPECT/CT in Parathyroid Scintigraphy: Is
      Additional Pinhole Imaging Useful?
AB  - Objectives: This retrospective study evaluated whether the use of additional
      anterior 99mTc-sestamibi/123I pinhole imaging improves the outcome of 99mTc
      sestamibi/123I subtraction SPECT/CT in parathyroid scintigraphy (PS). Materials
      and Methods: PS using simultaneous dual-isotope subtraction methods and an
      acquisition protocol combining SPECT/CT and planar pinhole imaging was performed
      for 175 patients with primary or secondary hyperparathyroidism. All patients who
      proceeded to surgery with complete postsurgery laboratory findings were included
      in this study (n = 94). SPECT/CT images alone and combined with pinhole images
      were evaluated. Results: There were 111 enlarged parathyroid glands of which 104
      and 108 glands were correctly visualized by SPECT/CT (seven false positives) or
      SPECT/CT with pinhole (three false positives), respectively. Both sensitivity and
      specificity were higher with combined SPECT/CT with pinhole than with SPECT/CT
      alone (97% versus 94% and 99% versus 98%, resp., not significant). The false
      positive rate was 6% with SPECT/CT and decreased to 3% using combined SPECT/CT
      with pinhole. Conclusion: 99mTc-sestamibi/123I subtraction SPECT/CT is a highly
      sensitive and specific protocol for PS. The use of additional anterior pinhole
      imaging increases both sensitivity and specificity of PS, although this increase
      is not statistically significant.

PMID- 29181197
TI  - Application of Real-Time 3D Navigation System in CT-Guided Percutaneous
      Interventional Procedures: A Feasibility Study.
AB  - Introduction: To evaluate the accuracy of a quantitative 3D navigation system for
      CT-guided interventional procedures in a two-part study. Materials and Methods:
      Twenty-two procedures were performed in abdominal and thoracic phantoms.
      Accuracies of the 3D anatomy map registration and navigation were evaluated. Time
      used for the navigated procedures was recorded. In the IRB approved clinical
      evaluation, 21 patients scheduled for CT-guided thoracic and hepatic biopsy and
      ablations were recruited. CT-guided procedures were performed without following
      the 3D navigation display. Accuracy of navigation as well as workflow fitness of
      the system was evaluated. Results: In phantoms, the average 3D anatomy map
      registration error was 1.79 mm. The average navigated needle placement accuracy
      for one-pass and two-pass procedures, respectively, was 2.0 +/- 0.7 mm and 2.8 +/
      1.1 mm in the liver and 2.7 +/- 1.7 mm and 3.0 +/- 1.4 mm in the lung. The
      average accuracy of the 3D navigation system in human subjects was 4.6 mm +/- 3.1
      for all procedures. The system fits the existing workflow of CT-guided
      interventions with minimum impact. Conclusion: A 3D navigation system can be
      performed along the existing workflow and has the potential to navigate precision
      needle placement in CT-guided interventional procedures.

PMID- 29181194
TI  - Physiological Roles of DNA Double-Strand Breaks.
AB  - Genomic integrity is constantly threatened by sources of DNA damage, internal and
      external alike. Among the most cytotoxic lesions is the DNA double-strand break
      (DSB) which arises from the cleavage of both strands of the double helix. Cells
      boast a considerable set of defences to both prevent and repair these breaks and
      drugs which derail these processes represent an important category of anticancer
      therapeutics. And yet, bizarrely, cells deploy this very machinery for the
      intentional and calculated disruption of genomic integrity, harnessing
      potentially destructive DSBs in delicate genetic transactions. Under tight
      spatiotemporal regulation, DSBs serve as a tool for genetic modification, widely
      used across cellular biology to generate diverse functionalities, ranging from
      the fundamental upkeep of DNA replication, transcription, and the chromatin
      landscape to the diversification of immunity and the germline. Growing evidence
      points to a role of aberrant DSB physiology in human disease and an understanding
      of these processes may both inform the design of new therapeutic strategies and
      reduce off-target effects of existing drugs. Here, we review the wide-ranging
      roles of physiological DSBs and the emerging network of their multilateral
      regulation to consider how the cell is able to harness DNA breaks as a critical
      biochemical tool.

PMID- 29181198
TI  - Effects of Long-Term Cultivation on Medium with Alpha-Ketoglutarate
      Supplementation on Metabolic Processes of Saccharomyces cerevisiae.
AB  - During last years, alpha-ketoglutarate (AKG), an important intermediate in the
      Krebs cycle, has been intensively studied as a dietary supplement with stress
      protective and potential antiaging effects. Here, we examined the effects of
      exogenous AKG on metabolic processes and survival of yeast Saccharomyces
      cerevisiae during long-term cultivation. Growth on AKG had no effect on the total
      cell number but increased the number of reproductively active cells at the late
      days of cultivation (from day 7 to day 15). A gradual increase in levels of total
      protein, glycogen, and trehalose was found over 7-day cultivation with more
      pronounced effects in AKG-grown cells. In control cells, metabolic activity and
      the activities of superoxide dismutase and catalase decreased, whereas levels of
      carbonyl proteins and low-molecular-mass thiols increased during 7-day
      cultivation. This suggests development of oxidative stress in stationary phase
      cells. Meanwhile, stationary phase cells cultured on AKG possessed higher levels
      of low-molecular-mass thiols and lower levels of carbonyl proteins and alpha
      dicarbonyl compounds when compared to control ones. Collectively, higher levels
      of storage carbohydrates and an activation of antioxidant defense with
      diminishing oxidative protein damage can prevent a loss of reproductive ability
      in yeast cells during long-term cultivation on AKG-supplemented medium.

PMID- 29181199
TI  - The Effects of Aerobic Exercise on the Recovery of Walking Ability and
      Neuroplasticity in People with Multiple Sclerosis: A Systematic Review of Animal
      and Clinical Studies.
AB  - Introduction: Walking is of high priority for people with multiple sclerosis
      (PwMS). It remains unclear whether aerobic exercise can improve walking ability
      and upregulate neurotrophins. This review aims to consolidate evidence to develop
      optimal aerobic training parameters to enhance walking outcomes and
      neuroplasticity in PwMS. Methods: Clinical studies examining aerobic exercise for
      >=3 weeks, having outcomes on walking with or without neurotrophic markers, were
      included. Studies utilizing animal models of MS were included if they employed
      aerobic exercise with outcomes on neurological recovery and neurotrophins. From a
      total of 1783 articles, 12 clinical and 5 animal studies were included. Results:
      Eleven clinical studies reported improvements in walking ability. Only two
      clinical studies evaluated both walking and neurotrophins, and neither found an
      increase in neurotrophins despite improvements in walking. Patients with
      significant walking impairments were underrepresented. Long-term follow-up
      revealed mixed results. Two animal studies reported a positive change in both
      neurological recovery and neurotrophins. Conclusion: Aerobic exercise improves
      walking ability in PwMS. Gains are not consistently maintained at 2- to 9-month
      follow-up. Studies examining levels of neurotrophins are inconclusive,
      necessitating further research. Aerobic exercise enhances both neurological
      recovery and neurotrophins in animal studies when started 2 weeks before
      induction of MS.

PMID- 29181193
TI  - In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the
      Structural Stability of G-Quadruplex Nucleic Acids?
AB  - Synthetic analogs of natural nucleotides have long been utilized for structural
      studies of canonical and noncanonical nucleic acids, including the extensively
      investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and
      nucleotide modifications of the folding landscape of GQs has been reviewed by
      several recent studies. Here, an overview is compiled on the thermodynamic
      stability of the modified GQ folds and on how the stereochemical preferences of
      more than 70 synthetic and natural derivatives of nucleotides substituting for
      natural ones determine the stability as well as the conformation. Groups of
      nucleotide analogs only stabilize or only destabilize the GQ, while the majority
      of analogs alter the GQ stability in both ways. This depends on the preferred syn
      or anti N-glycosidic linkage of the modified building blocks, the position of
      substitution, and the folding architecture of the native GQ. Natural base lesions
      and epigenetic modifications of GQs explored so far also stabilize or destabilize
      the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the
      stability of GQs can assist in engineering a required stable GQ topology, and
      exploring the in vitro action of the single and clustered natural base damage on
      GQ architectures may provide indications for the cellular events.

PMID- 29181200
TI  - Epidemiology of C2 Fractures in the 21st Century: A National Registry Cohort
      Study of 6,370 Patients from 1997 to 2014.
AB  - Objective: C2 fractures are a common injury in the elderly population. Treatment
      is often complicated due to osteoporosis and patient comorbidity. This study aims
      to investigate the incidence and treatment trend of C2 fractures in Sweden.
      Methods: Patients with the principal and secondary diagnosis of fracture of the
      second vertebrae (ICD-10: S12.1) between 1997 and 2014 were identified in the
      Swedish National Patient Registry (NPR). Results: Between 1997 and 2014, 6,370
      patients with a C2 fracture (51% male; age: 72 +/- 18) were identified in the
      NPR. The incidence of C2 fractures increased from 3 to 6 per 100,000 (r = 0.94; p
      < 0.01), mainly due to an increase of incidence in the geriatric subgroup (>=70
      years). The percentage of surgically treated patients decreased from 1997 to 2014
      (r = -0.80; p < 0.01). Younger age, male gender, spinal cord injury, and earlier
      year of admission were associated with surgical treatment assignment. Discussion:
      This study documents a rising incidence of C2 fractures in the elderly during the
      last two decades in Sweden. Greater awareness of fractures, improved diagnostics,
      coding, and a higher activity level of the patients are plausible causes. The
      declining trend of surgical treatment warrants further study.

PMID- 29181201
TI  - Sleep in the Postpartum: Characteristics of First-Time, Healthy Mothers.
AB  - Goals for the present study were to (a) describe the sleep of healthy new mothers
      over a 6-month postpartum period, (b) examine how sleep quality relates to
      daytime levels of fatigue and sleepiness, and (c) evaluate the relationship
      between mothers' and infants' sleep parameters. The sample consisted of 37
      healthy, partnered, first-time mothers who had experienced full-term vaginal
      birth and had a healthy infant. We investigated infants' sleep parameters and
      mothers' sleep, mood, and daytime functioning 2 and 6 months postpartum. We found
      that at 2 months postpartum, mothers reported sleeping 6 hours at night and just
      under one hour during the day. Despite relatively frequent nocturnal awakenings,
      mothers experienced minimal insomnia, nonrefreshing sleep, anxiety, depression,
      daytime sleepiness, or fatigue at either 2 or 6 months. The most robust
      relationship between mothers' and infants' sleep was in the number of nocturnal
      sleep-wake episodes. Of note is that none of the infant sleep parameters was
      related to mothers' anxiety, depression, fatigue, sleepiness, or nonrefreshing
      sleep at either time period. Our results indicate that (1) selected low risk new
      mothers are resilient in terms of sleep quality, daytime functioning, and mood
      and (2) these are independent of their infants' sleep parameters.

PMID- 29181203
TI  - Conducting Prolonged General Anesthesia without Intravenous Access in a Child
      with Hypoplastic Left Heart Syndrome.
AB  - Children with chronic medical conditions often need multiple intravenous (IV)
      access instances during their hospitalizations, both peripheral and central.
      Obtaining a working IV in this patient population undergoing general anesthesia
      can be challenging. In our case report, we describe a method of administering
      general anesthesia in an infant with partially repaired hypoplastic left heart
      syndrome without IV access.

PMID- 29181204
TI  - A Case of Invasive Pneumococcal Infection with Septic Shock and Rare
      Complications.
AB  - Invasive pneumococcus is a serious illness with potentially devastating outcomes.
      A 64-year-old female with a medical history of psoriatic arthritis and diabetes
      was transferred from an outside hospital for ventilator dependent respiratory
      failure and altered mental status. She initially presented with worsening back
      pain and was found to have leukocytosis with bandemia and acute renal failure but
      she was in septic shock upon arrival to our tertiary care center. Her blood
      cultures grew Streptococcus pneumoniae and MRI of the brain revealed pus within
      the posterior lateral ventricles and multiple infarcts. MRI of the spine revealed
      a psoas abscess. Transesophageal echocardiogram revealed mitral valve vegetation
      and her right eye developed endogenous endophthalmitis. She was treated with
      intravenous and intravitreal antibiotics and underwent drainage of the abscess
      with no improvement in mental status. Repeat imaging revealed multiple new
      thalamic, basal ganglia, and parietal lobe infarcts likely from septic emboli.
      After a protracted ICU stay, the patient's family opted for comfort care. The
      incidence of invasive pneumococcal infections has declined rapidly since the
      advent of antibiotics and vaccines. With the growing incidence of antibiotic
      resistance as well as the emergence of new immunomodulating drugs for various
      pathologies, there is a concern that invasive infections will reemerge.
      Ventriculitis and endogenous endophthalmitis are very rare complications of
      pneumococcal bacteremia.

PMID- 29181205
TI  - Basidiobolomycosis Simulating a Mycobacterium ulcerans Infection in a Togolese
      Rural Child.
AB  - Background: Basidiobolomycosis is a deep mycosis which preferentially affects
      rural young people in tropical countries. We report an atypical case, with
      multiple ulcers, simulating a Buruli ulcer. Case Report: A 5-year-old boy, living
      in a rural area, was seen for ulcers on the buttocks and at the back and right
      flank that had been in progress for 4 months. On examination, we found an
      infiltrated plaque with sharp edges, little painful, located on the buttocks,
      back, and the right flank. On this plaque, there were multiple ulcers with
      polycyclic contours and fibrinous bottom. There were inguinal inflammatory lymph
      nodes. The patient had an altered general condition. Examination of other organs
      was normal. The diagnosis of Buruli ulcer was evoked first; the search for
      Mycobacterium ulcerans by polymerase chain reaction was negative. Histology test
      performed revealed hypodermic granulomatous inflammation with predominant
      macrophage and eosinophils. The mycological culture was not done. The child was
      treated successfully with ketoconazole (10 mg/kg/day) during eight weeks.
      Discussion: Our observation shows great clinical and epidemiological similarities
      between basidiobolomycosis and Buruli ulcer. It confirms the efficacy of
      ketoconazole in severe basidiobolomycosis infection with alteration of general
      condition. Histopathology is very important for differential diagnosis between
      these two diseases.

PMID- 29181206
TI  - Atypical Histiocyte-Rich Sweet's Syndrome.
AB  - Sweet's Syndrome is a rare neutrophilic dermatosis thought to be a result of
      immune dysregulation occurring in the setting of drug exposure, recent infection,
      pregnancy, and underlying malignancy or idiopathic with specific and widely
      accepted diagnostic criteria established in the literature. Other organ systems
      can be involved with varying degrees of severity. An unusual case of Sweet's
      Syndrome associated with myopericarditis, acral involvement, and atypical
      histological findings with predominance of histiocytes is described here.

PMID- 29181207
TI  - Mycoplasma Pneumonia: An Unrecognized Cause of Fever of Unknown Origin in an
      Adult.
AB  - A 26-year-old female was admitted for fever of unknown origin (FUO), headaches,
      left ankle edema, and a lower extremity rash consistent with erythema nodosum.
      She had no respiratory symptoms or family history of autoimmune diseases. A chest
      X-ray was negative for pneumonia or hilar adenopathy. Extensive autoimmune workup
      was negative. A chest, abdomen, and pelvis computed tomography scan was
      unremarkable and laboratory studies revealed no source of infection. On hospital
      day 5, the patient developed a mild productive cough. Her Mycoplasma pneumonia
      (MP) IgM was high, confirming the diagnosis of MP induced FUO. She was started on
      azithromycin 500 mg daily and within 24 hours her fevers and headaches resolved.
      Her left ankle edema and EN gradually improved over a course of a few weeks. This
      case report highlights the need for MP testing in the evaluation of fever of
      unknown origin, even in the absence of pulmonary manifestations.

PMID- 29181202
TI  - Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep
      Disturbances, and Antidepressant Treatments.
AB  - Depression, which is characterized by a pervasive and persistent low mood and
      anhedonia, greatly impacts patients, their families, and society. The associated
      and recurring sleep disturbances further reduce patient's quality of life.
      However, therapeutic sleep deprivation has been regarded as a rapid and robust
      antidepressant treatment for several decades, which suggests a complicated role
      of sleep in development of depression. Changes in neural plasticity are observed
      during physiological sleep, therapeutic sleep deprivation, and depression. This
      correlation might help us to understand better the mechanism underlying
      development of depression and the role of sleep. In this review, we first
      introduce the structure of sleep and the facilitated neural plasticity caused by
      physiological sleep. Then, we introduce sleep disturbances and changes in
      plasticity in patients with depression. Finally, the effects and mechanisms of
      antidepressants and therapeutic sleep deprivation on neural plasticity are
      discussed.

PMID- 29181208
TI  - Large Retroperitoneal Haemorrhage Following Cyst Rupture in a Patient with
      Autosomal Dominant Polycystic Kidney Disease.
AB  - The complications of autosomal dominant polycystic kidney disease (ADPKD) include
      cyst rupture and haemorrhage leading to loin pain and frank haematuria. Risk
      factors include large kidney volume, hypertension, and renal impairment. We
      present a case of a young male who, following trauma to the kidney, had a life
      threatening bleed from his polycystic kidney. The case was initially treated with
      fluid resuscitation and blood transfusion but necessitated radiological
      embolization of bleeding source to control the blood loss. We review the risk
      factors and management of cyst haemorrhage in patients with ADPKD. Contact sports
      should be avoided as cyst rupture can lead to severe life threatening
      haemorrhage.

PMID- 29181209
TI  - Ureteropelvic Junction Obstruction and Parathyroid Adenoma: Coincidence or Link?
AB  - Congenital ureteropelvic junction obstruction (UPJO) is the most common cause of
      upper urinary tract obstruction in children. It is generally diagnosed in the
      routine work-up during antenatal period and is characterized by spontaneous
      recovery. It can be associated with urolithiasis; hence further investigation
      should be carried out. We report the case of a 15-year-old boy, who is known to
      have right UPJO, presented with right renal colic and discovered to have
      bilateral kidney stones. Further studies showed primary hyperparathyroidism and
      genetic analysis revealed a CDC73 mutation (initially HRPT2). We believe that
      association of UPJO and PHPT is a rare coincidence that can be linked. Careful
      work-up of children with UPJO and urolithiasis is recommended to exclude an
      underlying metabolic disease. Surgical correction can be evitable as treatment of
      the primary cause can lead to complete dissolution of kidney stones and
      improvement of the medical condition.

PMID- 29181210
TI  - Bilateral Tubal Pregnancy without Known Risk Factor.
AB  - Spontaneous bilateral ectopic gestation is very rare. The authors report a case
      diagnosed and taken care of at Yalgado Ouedraogo Teaching Hospital, Ouagadougou.
      It was a 30-year-old patient with no known pathological history. She had
      presented at the obstetric emergencies with a state of hypovolemic shock by
      haemoperitoneum with digestive disorders, pelvic pain, vaginal bleeding, and a
      mention of delayed menstruation. The ultrasound coupled with the urinary
      immunological pregnancy test confirmed the diagnosis of ruptured ectopic
      pregnancy and a bilateral form was suspected. A laparotomy in emergency confirmed
      the diagnosis of bilateral ectopic gestation with a right ampullary unruptured
      pregnancy and a left isthmic ruptured gestation. A bilateral salpingectomy was
      performed and counseling was made for the use of medical help of procreation in
      case of future need of pregnancy.

PMID- 29181211
TI  - Placenta Percreta in First Trimester after Multiple Rounds of Failed Medical
      Management for a Missed Abortion.
AB  - Background: The detection of a morbidly adherent placenta (MAP) in the first
      trimester is rare. Risk factors such as multiparity, advanced maternal age, prior
      cesarean delivery, prior myomectomy, placenta previa, or previous uterine
      evacuation place patients at a higher risk for having abnormal placental
      implantation. If these patients have a first trimester missed abortion and fail
      medical management, it is important that providers have a heightened suspicion
      for a MAP. Case: A 24-year-old G4P3003 with 3 prior cesarean deliveries underwent
      multiple rounds of failed medical management for a missed abortion. She had a
      dilation and curettage that was complicated by a significant hemorrhage and
      ultimately required an urgent hysterectomy. Conclusion: When patients fail
      medical management for a missed abortion, providers need to assess the patient's
      risk factors for a MAP. If risk factors are present, a series of specific
      evaluations should be triggered to rule out a MAP and help further guide
      management. Early diagnosis of a MAP allows providers to coordinate a
      multidisciplinary treatment approach and thoroughly counsel patients. Ensuring
      adequate resources and personnel at a tertiary hospital is essential to provide
      the highest quality of care and improve outcomes.

PMID- 29181212
TI  - Uncommon BRAF Mutations Associated with Durable Response to Immunotherapy in
      Patients with Metastatic Melanoma.
AB  - Melanoma is a disease process which has been increasing in incidence over the
      past three decades and metastatic melanoma carries a poor prognosis. Through
      genetic studies of this disease, it has been determined that the BRAF V600
      mutation plays a major role in the pathophysiology of the disease and this has
      led to the utilization of targeted therapy (BRAF and MEK inhibitors) in its
      treatment. Other BRAF mutations (non-V600 mutations) are rare in melanoma and
      targeted therapy is not indicated for patients with these mutations due to
      reduced response rates. An emerging option for metastatic melanoma with uncommon
      BRAF mutations is immunotherapy using checkpoint inhibitors such as PD-1
      inhibitors or CTLA-4 inhibitors. Currently, it is unknown how patients with BRAF
      non-V600 mutations respond to immunotherapy. This report will examine the effect
      of immunotherapy on two distinct metastatic melanoma patients, each with uncommon
      BRAF mutations, occurring outside the V600 locus (E586K and G469E). These
      patients were noted to have a durable, complete response when treated with
      immunotherapy and continue to exhibit a response 9 and 15 months after
      discontinuing therapy. Further research and clinical trials are needed to study
      patients with uncommon BRAF mutations and the potential therapeutic benefit of
      immunotherapy.

PMID- 29181213
TI  - Therapeutic Management of a Substantial Pelvic Aneurysmatic Bone Cyst Including
      the Off-Label Use of Denosumab in a 35-Year-Old Female Patient.
AB  - Aneurysmal bone cysts (ABC) are benign bone tumors, which are highly
      vascularized. The main course of treatment is curettage followed by bone grafting
      or cement insertion. Still recurrence remains a main problem for patients.
      Denosumab is a monoclonal antibody, which acts as an inhibitor of the RANK/RANKL
      pathway, diminishing bone turnover. Recent case reports have shown that Denosumab
      can be a promising therapeutic agent for people suffering from therapy-resistant
      ABC. We report the case of a 35-year-old female patient presenting with a
      pronounced ABC of the pelvis. Since the tumor was inoperable, Denosumab was
      administered, leading to a significant shrinkage of the lesion, which allowed
      surgical intervention. Upon recurrence, Denosumab was restarted putting the
      patient once more into remission. Follow-up was four years overall with a
      clinical and radiological stable disease for fifteen months after final
      discontinuation of the monoclonal antibody. Therefore, our case further
      underlines the potential of Denosumab in the treatment of ABC.

PMID- 29181214
TI  - Atypical Presentation of Sjogren-Larsson Syndrome.
AB  - Sjogren-Larsson syndrome is a rare neurocutaneous disorder characterized by
      ichthyosis, spastic diplegia or tetraplegia, and intellectual disability. Herein,
      we describe a case of a Greek patient with ichthyosis and spasticity of the legs
      but with normal intelligence (IQ 95). This syndrome should be suspected when a
      child presents with ichthyosis and spastic diplegia or tetraplegia, even if
      intelligence is normal.

PMID- 29181215
TI  - Electroconvulsive Therapy in Functional Hallucination: Scope and Challenges.
AB  - Functional hallucinations are hallucinations triggered by a stimulus in the same
      modality and cooccur with it. They are rare in occurrence; however, their rarity
      has no significance as psychopathology till date. Also, very little is known
      about the treatment of such hallucinations. Electroconvulsive therapy (ECT) has
      been tested for several psychiatric illnesses and has a few relative
      contraindications; however, it has not previously been used in treating
      functional hallucinations. We report on a female patient with paranoid
      schizophrenia who experienced functional hallucinations continuously despite the
      use of adequate risperidone, which controlled other symptoms. She was treated
      with ECT which resolved the functional hallucinations. The case highlights the
      need to ponder on the significance of the phenomenon as well as treatment of this
      psychopathology by ECT. It also underscores ECT as a treatment option for this
      kind of hallucination.

PMID- 29181216
TI  - Endovascular Repair with a Stent Graft in a Patient with Aortoduodenal Fistula
      after Radiation Therapy.
AB  - Primary aortoduodenal fistula (ADF) is a direct communication between the
      abdominal aorta and the gastrointestinal tract without any previous vascular
      intervention and represents a rare but critical cause of repeated and massive
      gastrointestinal bleeding. Primary ADF often occurs as a result of
      atherosclerotic aneurysm and infection, but ADF involving a normal-size aorta is
      rare; furthermore, ADF related to radiation therapy is extremely rare. We present
      the case of a 56-year-old man with a history of bowel obstruction due to
      radiation enteritis who was admitted with severe hematemesis and hemorrhagic
      shock. Gastroduodenal endoscopy and contrast-enhanced computed tomography
      findings were unremarkable. Aortoduodenal fistula was suspected based on the
      diffuse calcification of the abdominal aorta confined to the radiation field and
      the presence of an aortoduodenal communication on angiography. Endovascular
      repair with a stent graft seemed to be a safer option than open surgery and was
      suited to the rapid control of bleeding from ADF because of the patients'
      unstable hemodynamic state and the presence of intestinal adhesions. The fistula
      was successfully sealed by endovascular stent graft placement. Hematemesis did
      not recur postoperatively and anemia gradually improved. The patient died from
      pneumonia 33 days later.

PMID- 29181217
TI  - Traumatic Haemorrhagic Cervical Lymphadenopathy with Underlying Infectious
      Mononucleosis.
AB  - A 16-year-old male presented to the Emergency Department with a painful 3 * 3 cm
      left-sided neck swelling six hours following blunt trauma to the neck from a
      heavy swinging door. A CT angiogram was performed which revealed a large
      haemorrhagic lymph node as well as generalised cervical lymphadenopathy. The
      patient was eventually diagnosed with infectious mononucleosis. This case report
      describes a rare case of traumatic haemorrhagic cervical lymphadenopathy with an
      underlying diagnosis of infectious mononucleosis.

PMID- 29181218
TI  - Superinfection of a Dead Hepatic Echinococcal Cyst with a Cutaneous
      Fistulization.
AB  - Cystic echinococcosis (CE), also known as "hydatid disease" (HD), is a zoonotic
      infection caused by the larval stage of Echinococcus granulosus, which infects
      humans as intermediate hosts through the orofecal route. Carried by the
      intestinal venous blood, the embryos released by the eggs of the tapeworms can
      reach every organ, especially the liver, turning into a hydatid cyst. Usually
      asymptomatic, the cysts can be incidentally detected through radiological
      examinations performed for other reasons. We show an unusual case of
      superinfection of a hydatid cyst with typical radiological features of inactivity
      (WHO-type CE5) with an even rarer skin fistulization passing through a
      subcutaneous-abdominal abscess involving the right iliac muscle.

PMID- 29181220
TI  - Angio-SealTM Embolization: A Rare Etiology of an Acute Distal Limb Ischemia.
AB  - We herein report a serious vascular complication of diagnostic cardiac
      catheterization due to an embolization of an Angio-Seal closure device causing
      acute lower limb ischemia. The Angio-Seal was deployed via the right femoral
      artery following the catheterization which embolized several hours later to the
      right popliteal artery. Fogarty embolectomy restored perfusion to the right lower
      limb; however, compartment syndrome subsequently developed which required
      evacuation of a hematoma and repair of right popliteal artery.

PMID- 29181219
TI  - Idiopathic Giant Hepatic Artery Pseudoaneurysm.
AB  - Hepatic artery pseudoaneurysm (HAP) incidence is rising due to more common use of
      endoscopic and percutaneous hepatic interventions. HAP is potentially fatal, as
      it could lead to sudden life-threatening hemorrhage. HAP can be intrahepatic or
      extrahepatic. On computed tomography angiogram (CTA) and magnetic resonance
      angiogram (MRA), HAP follows blood pool on multiphasic examination, with brisk
      arterial enhancement that washes out, similar to the abdominal aorta on later
      phases. We present a case of idiopathic giant HAP in an 82-year-old male.
      Currently, angioembolization is replacing surgery as the initial modality of
      choice for management of this condition.

PMID- 29181221
TI  - Electroanalytical Sensing of Bromides Using Radiolytically Synthesized Silver
      Nanoparticle Electrocatalysts.
AB  - Monitoring bromides (Br-) is of crucial importance since bromates, potential
      human carcinogens, are formed during ozonation of water containing bromides in
      concentrations >100 MUg L-1. Within this study, silver (Ag) and four carbon
      supported Ag catalysts were synthesized by the gamma-radiation method and their
      morphology and structure examined using transmission electron microscopy, X-ray
      diffraction, and UV-Vis analysis. The nanocatalysts were tested for Br- sensing
      in aqueous media using cyclic voltammetry. All five Ag materials exhibited
      electroactivity for sensing of Br- ions, with pure Ag catalyst giving the best
      response to Br- ions presence in terms of the lowest limit of detection. Sensing
      of bromides was also explored in tap water after addition of bromides suggesting
      that herein prepared catalysts could be used for bromides detection in real
      samples. Furthermore, sensing of other halogen ions, namely, chlorides and
      iodides, was examined, and response due to chloride presence was recorded.

PMID- 29181222
TI  - Validation of an UHPLC-MS/MS Method for Screening of Antimicrobial Residues in
      Eggs and Their Application to Analyses of Eggs from Laying Hens Subjected to
      Pharmacological Treatment.
AB  - A multiresidue method by UHPLC/MS-MS was optimized and validated for the
      screening and semiquantitative detection of antimicrobials residues from
      tetracyclines, aminoglycosides, quinolones, lincosamides, beta-lactams,
      sulfonamides, and macrolides families in eggs. A qualitative approach was used to
      ensure adequate sensitivity to detect residues at the level of interest, defined
      as maximum residue limit (MRL), or less. The applicability of the methods was
      assessed by analyzing egg samples from hens that had been subjected to
      pharmacological treatment with neomycin, enrofloxacin, lincomycin,
      oxytetracycline, and doxycycline during five days and after discontinuation of
      medication (10 days). The method was adequate for screening all studied analytes
      in eggs, since the performance parameters ensured a false-compliant rate below or
      equal to 5%, except for flumequine. In the analyses of eggs from laying hens
      subjected to pharmacological treatment, all antimicrobial residues were detected
      throughout the experimental period, even after discontinuation of medication,
      except for neomycin, demonstrating the applicability of the method for analyses
      of antimicrobial residues in eggs.

PMID- 29181223
TI  - The Evidence of Cooperative Binding of a Ligand to G4 DNA.
AB  - Intrinsic constants of the ligand binding with G4 DNA (guanine-rich DNA sequence)
      using quantitative standards can be convenient providing the assessment for
      elucidating the possibility of such structures participation in biochemical
      processes. In the present communication, the hard + soft modelling approach to
      calculate intrinsic constants of a ligand binding with short DNA molecule,
      particularly such as G4 DNA, has been proposed. The suggested approach has
      focused upon the quantitative evaluating of a mutual influence between sites and
      between bound ligands. The cross-validation between a new hard + soft modelling
      and conventional stepwise complex formation algorithm has been conducted. A
      number of simulated examples will illustrate the methodology. The experimental
      mole-ratio titration of TMPyP4 by G4 DNA [(CG3)2CGC(AG3)2G] has been reexamined.
      The [(CG3)2CGC(AG3)2G] that folds from a G-rich sequence found in the promoter
      region of c-kit oncogene can be considered as a molecule with two equivalent
      mutually influence binding sites.

PMID- 29181224
TI  - Application of 19F NMR Spectroscopy for Content Determination of Fluorinated
      Pharmaceuticals.
AB  - A simple, rapid, and selective quantitative nuclear magnetic resonance
      spectroscopic method was evaluated for the determination of the content of
      fluorinated pharmaceuticals. 19F NMR spectra were either obtained in
      dimethylsulfoxide-d6 or aqueous buffer, using trifluoroacetic acid as internal
      standard. Quantification of 13 fluorine-containing pharmaceuticals spanning
      various pharmacological classes was accomplished using the proposed method. The
      method was found to be fit for purpose (interday precision 1.2% relative standard
      deviation) and may thus be applied for routine analysis and quality control of
      fluorine-containing pharmaceuticals due to its simplicity, nondestructive sample
      measurement, reliability, and high specificity. Therefore, 19F NMR may serve as a
      suitable analytical tool for the identification and selective determination of
      fluorinated pharmaceuticals used as reference materials and bulk samples.

PMID- 29181225
TI  - Assessment of the Efficacy of Home Remedial Methods to Improve Drinking Water
      Quality in Two Major Aquifer Systems in Jaffna Peninsula, Sri Lanka.
AB  - Chunnakam and Vadamaradchi are two major aquifer systems in Jaffna Peninsula, Sri
      Lanka. This study was performed to compare water quality in the domestic wells in
      these aquifers and to assess the efficacy of household water treatments for
      treating contaminated water. Replicate well water samples were collected from
      each aquifer and pH, dissolved oxygen (DO), conductivity, total dissolved solids
      (TDS), salinity, temperature, total solids (TS), total hardness (TH), chemical
      oxygen demand (COD), oil and grease (OG), nitrate N (N), and total phosphate (TP)
      were measured. The sampled water from the domestic wells was filtered through
      commercial mineral filter and Moringa oleifera leaf powder and boiled at 100
      degrees C for 10 minutes and the TH, OG, N, and TP were measured. Both OG and N
      in Chunnakam were significantly higher and the DO were significantly lower than
      those of Vadamaradchi. TH, N, and OG of some wells exceeded the drinking water
      quality standards established by Sri Lanka Standards Institution. Moringa
      oleifera leaf powder filtration reduced N significantly and filtering through
      commercial mineral filter reduced OG, TH, and N significantly. Boiling at 100
      degrees C could remove TH significantly but may cause significant increase in N
      which might result in health impacts.

PMID- 29181226
TI  - Blood Safety Status in WHO African Region Countries: Lessons Learnt from
      Mauritius.
AB  - In 2001, the WHO Office for Africa adopted a strategy for blood safety defining
      four targets. This paper describes the progress made by Mauritius in the
      implementation of this strategy. The blood safety indicators were collected and
      compared with the norms recommended by WHO. The country has formulated its blood
      policy and developed a strategic plan for its implementation since 2004. The
      total number of blood donations increased from 31,228 in 2002 to 43,742 in 2016,
      giving an annual blood collection rate evolving from 26.3 per 1000 inhabitants in
      2002 to 34.2 per 1000 inhabitants in 2016. The percentage of voluntary donations
      rose from 60% to 82.5%. Since 2002, all the blood units collected have been
      tested for the mandatory infectious markers. The Blood Transfusion Service has
      been certified ISO2008-9001 and nucleic acid testing has been introduced. The
      preparation of blood components increased from 60% to 98.2%. The most transfused
      blood components were red cell concentrates, platelet concentrates, and fresh
      frozen plasma. In addition to transfusion activities, there were other
      departments performing antenatal serology, tissue typing, special investigations,
      and reagent preparation. Despite the progress made, some challenges remain,
      namely, legal framework and haemovigilance system. A regulatory system for blood
      needs to be established.

PMID- 29181227
TI  - Dengue: The break-bone fever outbreak in Kerala, India.

PMID- 29181228
TI  - Knowledge of warning signs, presenting symptoms and risk factors of coronary
      heart disease among the population of Dubai and Northern Emirates in UAE: a cross
      sectional study.
AB  - Background: To evaluate the level of knowledge regarding warning signs,
      presenting symptoms and risk factors associated with coronary heart disease (CHD)
      among population of Dubai and Northern Emirates in UAE. Materials and Methods: A
      cross sectional survey of 1367 residents of Dubai and Northern Emirates was
      conducted using a self-administered questionnaire. Results: Respondents were
      classified into two groups: Young Adult Population (YAP; 18-24 years of age) and
      General Population (GP; 25 years and older). Majority of participants were males
      (56.7%) and of South Asian (57.5%) or Middle-Eastern (30.8%) ethnicity. Regarding
      presenting symptoms of CHD, chest pain was identified by around 80% of
      population, whereas pain in the left shoulder was recognized by 61% of GP and 44%
      of YAP. Atypical symptoms were poorly identified. Regarding risk factors, only
      one-fourth population knew that males were at higher risk compared to
      premenopausal females. Few knew that the risk increases in females after
      menopause and that the risk is higher for females who smoke and use oral
      contraceptives. 62% knew that the survivors of a heart attack are at high risk of
      recurrences. Except for tobacco smoke, hypercholesterolemia and hypertension,
      knowledge of other risk factors was not satisfactory. Older adults and females
      had comparatively higher level of knowledge. Conclusion: Knowledge level of many
      of the symptoms and risk factors of CHD is unsatisfactory. There is, therefore, a
      need to increase the awareness in the population of UAE. The knowledge gaps
      identified through this study can be addressed through health campaigns to
      increase the awareness about warning signs, symptoms and modifiable risk factors.
      .

PMID- 29181229
TI  - Lexis Expansion: a prerequisite for analyzing time changing variables in a cohort
      study.
AB  - In a prospective analytical cohort study or a study involving a longer follow up,
      changing age of participants influence the relationship between exposure and
      outcome. Usually age at entry is incorporated in the regression model to adjust
      for age. However, this fails to fully explain and adjust for changing age. For
      this Lexis expansion, a concept by Wilhelm Lexis, allows the analyst to expand
      the observations as per age bands and check for confounding and interaction by
      changing age. Lexis expansion assumes the rates to be constant within an age
      band.

PMID- 29181231
TI  - Remembering Our Roots.

PMID- 29181230
TI  - Fungal keratitis: study of increasing trend and common determinants.
AB  - Fungal keratitis is one of the leading cause of ocular morbidity. Fungal
      keratitis possesses a clinical challenge due to its slow pathologic process,
      overlapping features, diagnostic difficulty, and potential complications. Its
      increasing trend can be attributed to the use of contact lens, non-judiciary
      corticosteroid, and vegetative trauma. Early diagnosis and treatment is the
      cornerstone for its effective control. Knowledge of pathological course and
      clinical characteristics of fungal keratitis will definitely add in early
      diagnosis and treatment, with reduction in ocular morbidity. This review article
      explores the risk factor of fungal keratitis, its clinical course and management
      strategy.

PMID- 29181232
TI  - Machine Learning to Compare Frequent Medical Problems of African American and
      Caucasian Diabetic Kidney Patients.
AB  - Objectives: End-stage renal disease (ESRD), which is primarily a consequence of
      diabetes mellitus, shows an exemplary health disparity between African American
      and Caucasian patients in the United States. Because diabetic chronic kidney
      disease (CKD) patients of these two groups show differences in their medical
      problems, the markers leading to ESRD are also expected to differ. The purpose of
      this study was, therefore, to compare their medical complications at various
      levels of kidney function and to identify markers that can be used to predict
      ESRD. Methods: The data of type 2 diabetic patients was obtained from the 2012
      Cerner database, which totaled 1,038,499 records. The data was then filtered to
      include only African American and Caucasian outpatients with estimated glomerular
      filtration rates (eGFR), leaving 4,623 records. A priori machine learning was
      used to discover frequently appearing medical problems within the filtered data.
      CKD is defined as abnormalities of kidney structure, present for >3 months.
      Results: This study found that African Americans have much higher rates of CKD
      related medical problems than Caucasians for all five stages, and prominent
      markers leading to ESRD were discovered only for the African American group.
      These markers are high glucose, high systolic blood pressure (BP), obesity,
      alcohol/drug use, and low hematocrit. Additionally, the roles of systolic BP and
      diastolic BP vary depending on the CKD stage. Conclusions: This research
      discovered frequently appearing medical problems across five stages of CKD and
      further showed that many of the markers reported in previous studies are more
      applicable to African American patients than Caucasian patients.

PMID- 29181233
TI  - Development and Application of Direct Data Capture for Monitoring Medication
      Compliance in Clinical Trials.
AB  - Objectives: The monitoring of medication compliance in clinical trials is
      important but labor intensive. To check medication compliance in clinical trials,
      a system was developed, and its technical feasibility evaluated. Methods: The
      system consisted of three parts: a management part (clinical trial center
      database and a developed program), clinical trial investigator part (monitoring),
      and clinical trial participant part (personal digital assistant [PDA] with a
      barcode scanner). The system was tested with 20 participants for 2 weeks, and
      compliance was evaluated. Results: This study developed a medication compliance
      monitoring system that used a PDA with a barcode scanner, which sent
      reminder/warning messages, logged medication barcode data, and provided
      compliance information to investigators. Registered participants received short
      message service (SMS) reminder/warning messages on their PDA and sent barcode
      data at the dosing time. The age range of the participants was 29 to 73 years.
      Five participants were <50 years old and 8 were >=65 years old. The total mean
      compliance rate was 82.3%. The mean compliance rate was 83.1% in participants <65
      years old and 81.1% in those >=65 years old. Conclusions: The system was
      feasible, usable, and effective, even with elderly participants, for monitoring
      medication compliance in clinical trials using a PDA with a barcode scanner, and
      may improve the quality of clinical trials.

PMID- 29181234
TI  - Clinical Decision Support Model to Predict Occlusal Force in Bruxism Patients.
AB  - Objectives: The aim of this study was to develop a decision support model for the
      prediction of occlusal force from the size and color of articulating paper
      markings in bruxism patients. Methods: We used the information from the datasets
      of 30 bruxism patients in which digital measurements of the size and color of
      articulating paper markings (12-um Hanel; Coltene/Whaledent GmbH, Langenau,
      Germany) on canine protected hard stabilization splints were measured in pixels
      (P) and in red (R), green (G), and blue (B) values using Adobe Photoshop software
      (Adobe Systems, San Jose, CA, USA). The occlusal force (F) was measured using T
      Scan III (Tekscan Inc., South Boston, MA, USA). The multiple regression equation
      was applied to predict F from the P and RGB. Model evaluation was performed using
      the datasets from 10 new patients. The patient's occlusal force measured by T
      Scan III was used as a 'gold standard' to compare with the occlusal force
      predicted by the multiple regression model. Results: The results demonstrate that
      the correlation between the occlusal force and the pixels and RGB of the
      articulating paper markings was positive (F = 1.62*P + 0.07*R -0.08*G + 0.08*B +
      4.74; R2 = 0.34). There was a high degree of agreement between the occlusal force
      of the patient measured using T-Scan III and the occlusal force predicted by the
      model (kappa value = 0.82). Conclusions: The results obtained demonstrate that
      the multiple regression model can predict the occlusal force using the digital
      values for the size and color of the articulating paper markings in bruxism
      patients.

PMID- 29181235
TI  - Systematic Review of Data Mining Applications in Patient-Centered Mobile-Based
      Information Systems.
AB  - Objectives: Smartphones represent a promising technology for patient-centered
      healthcare. It is claimed that data mining techniques have improved mobile apps
      to address patients' needs at subgroup and individual levels. This study reviewed
      the current literature regarding data mining applications in patient-centered
      mobile-based information systems. Methods: We systematically searched PubMed,
      Scopus, and Web of Science for original studies reported from 2014 to 2016. After
      screening 226 records at the title/abstract level, the full texts of 92 relevant
      papers were retrieved and checked against inclusion criteria. Finally, 30 papers
      were included in this study and reviewed. Results: Data mining techniques have
      been reported in development of mobile health apps for three main purposes: data
      analysis for follow-up and monitoring, early diagnosis and detection for
      screening purpose, classification/prediction of outcomes, and risk calculation (n
      = 27); data collection (n = 3); and provision of recommendations (n = 2). The
      most accurate and frequently applied data mining method was support vector
      machine; however, decision tree has shown superior performance to enhance mobile
      apps applied for patients' self-management. Conclusions: Embedded data-mining
      based feature in mobile apps, such as case detection, prediction/classification,
      risk estimation, or collection of patient data, particularly during self
      management, would save, apply, and analyze patient data during and after care.
      More intelligent methods, such as artificial neural networks, fuzzy logic, and
      genetic algorithms, and even the hybrid methods may result in more patients
      centered recommendations, providing education, guidance, alerts, and awareness of
      personalized output.

PMID- 29181236
TI  - Machine Learning to Improve the Effectiveness of ANRS in Predicting HIV Drug
      Resistance.
AB  - Objectives: Human immunodeficiency virus infection and acquired immune deficiency
      syndrome (HIV/AIDS) is one of the major burdens of disease in developing
      countries, and the standard-of-care treatment includes prescribing antiretroviral
      drugs. However, antiretroviral drug resistance is inevitable due to selective
      pressure associated with the high mutation rate of HIV. Determining
      antiretroviral resistance can be done by phenotypic laboratory tests or by
      computer-based interpretation algorithms. Computer-based algorithms have been
      shown to have many advantages over laboratory tests. The ANRS (Agence Nationale
      de Recherches sur le SIDA) is regarded as a gold standard in interpreting HIV
      drug resistance using mutations in genomes. The aim of this study was to improve
      the prediction of the ANRS gold standard in predicting HIV drug resistance.
      Methods: A genome sequence and HIV drug resistance measures were obtained from
      the Stanford HIV database (http://hivdb.stanford.edu/). Feature selection was
      used to determine the most important mutations associated with resistance
      prediction. These mutations were added to the ANRS rules, and the difference in
      the prediction ability was measured. Results: This study uncovered important
      mutations that were not associated with the original ANRS rules. On average, the
      ANRS algorithm was improved by 79% +/- 6.6%. The positive predictive value
      improved by 28%, and the negative predicative value improved by 10%. Conclusions:
      The study shows that there is a significant improvement in the prediction ability
      of ANRS gold standard.

PMID- 29181237
TI  - Prediction of Kidney Graft Rejection Using Artificial Neural Network.
AB  - Objectives: Kidney transplantation is the best renal replacement therapy for
      patients with end-stage renal disease. Several studies have attempted to identify
      predisposing factors of graft rejection; however, the results have been
      inconsistent. We aimed to identify prognostic factors associated with kidney
      transplant rejection using the artificial neural network (ANN) approach and to
      compare the results with those obtained by logistic regression (LR). Methods: The
      study used information regarding 378 patients who had undergone kidney
      transplantation from a retrospective study conducted in Hamadan, Western Iran,
      from 1994 to 2011. ANN was used to identify potential important risk factors for
      chronic nonreversible graft rejection. Results: Recipients' age, creatinine
      level, cold ischemic time, and hemoglobin level at discharge were identified as
      the most important prognostic factors by ANN. The ANN model showed higher total
      accuracy (0.75 vs. 0.55 for LR), and the area under the ROC curve (0.88 vs. 0.75
      for LR) was better than that obtained with LR. Conclusions: The results of this
      study indicate that the ANN model outperformed LR in the prediction of kidney
      transplantation failure. Therefore, this approach is a promising classifier for
      predicting graft failure to improve patients' survival and quality of life, and
      it should be further investigated for the prediction of other clinical outcomes.

PMID- 29181238
TI  - Development of a Stress Classification Model Using Deep Belief Networks for
      Stress Monitoring.
AB  - Objectives: Stress management is related to public healthcare and quality of
      life; an accurate stress classification method is necessary for the design of
      stress monitoring systems. Therefore, the goal of this study was to design a
      novel stress classification model using a deep learning method. Methods: In this
      paper, we present a stress classification model using the dataset from the sixth
      Korea National Health and Nutrition Examination Survey conducted from 2013 to
      2015 (KNHANES VI) to analyze stress-related health data. Statistical analysis was
      performed to identify the nine features of stress detection, and we evaluated the
      performance of the proposed stress classification by comparison with several
      stress detection models. The proposed model was also evaluated using Deep Belief
      Networks (DBN). Results: We designed profiles depending on the number of hidden
      layers, nodes, and hyper-parameters according to the loss function results. The
      experimental results showed that the proposed model achieved an accuracy and a
      specificity of 66.23% and 75.32%, respectively. The proposed DBN model performed
      better than other classification models, such as support vector machine, naive
      Bayesian classifier, and random forest. Conclusions: The proposed model in this
      study was demonstrated to be effective in classifying stress detection, and in
      particular, it is expected to be applicable for stress prediction in stress
      monitoring systems.

PMID- 29181239
TI  - Validity of Principal Diagnoses in Discharge Summaries and ICD-10 Coding
      Assessments Based on National Health Data of Thailand.
AB  - Objectives: This study examined the validity of the principal diagnoses on
      discharge summaries and coding assessments. Methods: Data were collected from the
      National Health Security Office (NHSO) of Thailand in 2015. In total, 118,971
      medical records were audited. The sample was drawn from government hospitals and
      private hospitals covered by the Universal Coverage Scheme in Thailand. Hospitals
      and cases were selected using NHSO criteria. The validity of the principal
      diagnoses listed in the "Summary and Coding Assessment" forms was established by
      comparing data from the discharge summaries with data obtained from medical
      record reviews, and additionally, by comparing data from the coding assessments
      with data in the computerized ICD (the data base used for reimbursement
      purposes). Results: The summary assessments had low sensitivities (7.3%-37.9%),
      high specificities (97.2%-99.8%), low positive predictive values (9.2%-60.7%),
      and high negative predictive values (95.9%-99.3%). The coding assessments had low
      sensitivities (31.1%-69.4%), high specificities (99.0%-99.9%), moderate positive
      predictive values (43.8%-89.0%), and high negative predictive values (97.3%
      99.5%). The discharge summaries and codings often contained mistakes,
      particularly the categories "Endocrine, nutritional, and metabolic diseases",
      "Symptoms, signs, and abnormal clinical and laboratory findings not elsewhere
      classified", "Factors influencing health status and contact with health
      services", and "Injury, poisoning, and certain other consequences of external
      causes". Conclusions: The validity of the principal diagnoses on the summary and
      coding assessment forms was found to be low. The training of physicians and
      coders must be strengthened to improve the validity of discharge summaries and
      codings.

PMID- 29181240
TI  - Satisfaction with Paper-Based Dental Records and Perception of Electronic Dental
      Records among Dental Professionals in Myanmar.
AB  - Objectives: To overcome challenges in the implementation of electronic dental
      record systems in a low-resource setting, it is crucial to know the level of
      users' satisfaction with the existing system of paper-based dental records and
      their perceptions of electronic dental records. Methods: A cross-sectional paper
      based questionnaire survey was conducted among Myanmar dental professionals who
      worked in one of two teaching hospitals or in private dental clinics. Descriptive
      data were analyzed and regression analysis was carried out to identify factors
      influencing perceptions of electronic dental records. Results: Most dental
      professionals (>60%) were satisfied with just three out of six aspects of paper
      based dental records (familiarity, flexibility, and portability). In addition,
      generalized positive perceptions were found among decision makers towards
      electronic dental records, and 86% of dentists indicated that they were willing
      to use them. Financial concerns were identified as the most important barrier to
      the implementation of electronic dental records among dentists who were not
      willing to use the proposed system. Conclusions: The first step towards
      implementing electronic dental records in Myanmar should be improvement of the
      content and structure of paper-based dental records, especially in private dental
      clinics. Utilization of appropriate open-source electronic dental record software
      in private dental clinics is recommended to address perceived issues around
      financial barriers. For the long term, we recommend providing further education
      and training in health informatics to healthcare professionals to facilitate the
      efficient use of electronic dental record software in Myanmar in the future.

PMID- 29181241
TI  - Technology and Policy Challenges in the Adoption and Operation of Health
      Information Exchange Systems.
AB  - Objectives: This study aimed to identify problems and issues that arise with the
      implementation of online health information exchange (HIE) systems in a medical
      environment and to identify solutions to facilitate the successful operation of
      future HIE systems in primary care clinics and hospitals. Methods: In this study,
      the issues that arose during the establishment and operation of an HIE system in
      a hospital were identified so that they could be addressed to enable the
      successful establishment and operation of a standard-based HIE system. After the
      issues were identified, they were reviewed and categorized by a group of experts
      that included medical information system experts, doctors, medical information
      standard experts, and HIE researchers. Then, solutions for the identified
      problems were derived based on the system development, operation, and improvement
      carried out during this work. Results: Twenty-one issues were identified during
      the implementation and operation of an online HIE system. These issues were then
      divided into four categories: system architecture and standards, documents and
      data items, consent of HIE, and usability. We offer technical and policy
      recommendations for various stakeholders based on the experiences of operating
      and improving the online HIE system in the medical field. Conclusions: The issues
      and solutions identified in this study regarding the implementation and operate
      of an online HIE system can provide valuable insight for planners to enable them
      to successfully design and operate such systems at a national level in the
      future. In addition, policy support from governments is needed.

PMID- 29181242
TI  - Association between Health Information Technology and Case Mix Index.
AB  - Objectives: Health information technology (IT) can assist healthcare providers in
      ordering medication and adhering to guidelines while improving communication
      among providers and the quality of care. However, the relationship between health
      IT and Case Mix Index (CMI) has not been thoroughly investigated; therefore, this
      study aimed to clarify this relationship. Methods: To examine the effect of
      health IT on CMI, a generalized estimation equation (GEE) was applied to two
      years of California hospital data. Results: We found that IT was positively
      associated with CMI, indicating that increased IT adoption could lead to a higher
      CMI or billing though DRG up-coding. This implies that hospitals' revenue could
      increase around $40,000 by increasing IT investment by 10%. Conclusions: The
      positive association between IT and CMI implies that IT adoption itself could
      lead to higher patient billings. Generally, a higher CMI in a hospital indicates
      that the hospital provides expensive services with higher coding and therefore
      receives more money from patients. Therefore, measures to prevent upcoding
      through IT systems should be implemented.

PMID- 29181243
TI  - Development and Cross-cultural Validation of the Korean Version of SMArtphone's
      uSability Heuristics (SMASH).
AB  - Objectives: The purpose of this study was to develop and cross-culturally
      validate the Korean version of SMArtphone's uSability Heuristics (K-SMASH).
      Methods: In the study, it was used the adaptation process consisted of five
      stages, namely, translation, synthesis, back translation, expert committee
      review, and pretesting. In the pretesting stage, a mobile application, using the
      prefinal K-SMASH, was evaluated for the severity of usability problems by three
      experts in computer science and informatics. Each participant completed the
      evaluation and was interviewed about their understanding, interpretation, and
      opinion of the cultural relevance of the prefinal K-SMASH. Next, we reviewed the
      differences in the experts' opinions and the questionnaire results. Results:
      Twelve SMASH items, words and sentences, were translated, back translated, and
      revised, considering the conceptual meaning in the context of the Korean culture,
      by experts in various fields, including a Korean linguist and a bilingual
      translator, through the first stage to the fourth stage. In the pretesting stage,
      the results showed no major differences among the severity ratings of
      participants. Furthermore, all participants answered that there were no critical
      discrepancies or inconsistencies with the cultural relevance of the prefinal K
      SMASH. Conclusions: The results of the study provide preliminary evidence that
      the modified K-SMASH can be used for heuristic evaluation, one of the usability
      tests, when developing applications in Korea.

PMID- 29181244
TI  - System for Collecting Biosignal Data from Multiple Patient Monitoring Systems.
AB  - Objectives: Biosignal data include important physiological information. For that
      reason, many devices and systems have been developed, but there has not been
      enough consideration of how to collect and integrate raw data from multiple
      systems. To overcome this limitation, we have developed a system for collecting
      and integrating biosignal data from two patient monitoring systems. Methods: We
      developed an interface to extract biosignal data from Nihon Kohden and Philips
      monitoring systems. The Nihon Kohden system has a central server for the
      temporary storage of raw waveform data, which can be requested using the HL7
      protocol. However, the Philips system used in our hospital cannot save raw
      waveform data. Therefore, our system was connected to monitoring devices using
      the RS232 protocol. After collection, the data were transformed and stored in a
      unified format. Results: From September 2016 to August 2017, we collected
      approximately 117 patient-years of waveform data from 1,268 patients in 79 beds
      of five intensive care units. Because the two systems use the same data storage
      format, the application software could be run without compatibility issues.
      Conclusions: Our system collects biosignal data from different systems in a
      unified format. The data collected by the system can be used to develop
      algorithms or applications without the need to consider the source of the data.

PMID- 29181245
TI  - Usages of Computers and Smartphones to Develop Dementia Care Education Program
      for Asian American Family Caregivers.
AB  - Objectives: Families of ethnic minority persons with dementia often seek help at
      later stages of the disease. Little is known about the effectiveness of various
      methods in supporting ethnic minority dementia patients' caregivers. The
      objective of the study was to identify smartphone and computer usage among family
      caregivers of dementia patients (i.e., Korean and Vietnamese Americans) to
      develop dementia-care education programs for them. Methods: Participants were
      asked various questions related to their computer or smartphone usage in
      conjunction with needs-assessment interviews. Flyers were distributed at two
      ethnic minority community centers in Southern California. Snowball recruitment
      was also utilized to reach out to the families of dementia patients dwelling in
      the community. Results: Thirty-five family caregivers, including 20 Vietnamese
      and 15 Korean individuals, participated in this survey. Thirty participants (30
      of 35, 85.7%) were computer users. Among those, 76.7% (23 of 30) reported daily
      usage and 53% (16 of 30) claimed to use social media. A majority of the
      participants (31 of 35, 88.6%) reported that they owned smartphones. More than
      half of smartphone users (18 of 29, 62%) claimed to use social media
      applications. Many participants claimed that they could not attend in-class
      education due to caregiving and/or transportation issues. Conclusions: Most
      family caregivers of dementia patients use smartphones more often than computers,
      and more than half of those caregivers communicate with others through social
      media apps. A smartphone-app-based caregiver intervention may serve as a more
      effective approach compared to the conventional in-class method. Multiple
      modalities for the development of caregiver interventions should be considered.

PMID- 29181246
TI  - Methods Using Social Media and Search Queries to Predict Infectious Disease
      Outbreaks.
AB  - Objectives: For earlier detection of infectious disease outbreaks, a digital
      syndromic surveillance system based on search queries or social media should be
      utilized. By using real-time data sources, a digital syndromic surveillance
      system can overcome the limitation of time-delay in traditional surveillance
      systems. Here, we introduce an approach to develop such a digital surveillance
      system. Methods: We first explain how the statistics data of infectious diseases,
      such as influenza and Middle East Respiratory Syndrome (MERS) in Korea, can be
      collected for reference data. Then we also explain how search engine queries can
      be retrieved from Google Trends. Finally, we describe the implementation of the
      prediction model using lagged correlation, which can be calculated by the
      statistical packages, i.e., SPSS (Statistical Package for the Social Sciences).
      Results: Lag correlation analyses demonstrated that search engine data/Twitter
      have a significant temporal relationship with influenza and MERS data. Therefore,
      the proposed digital surveillance system can be used to predict infectious
      disease outbreaks earlier. Conclusions: This prediction method could be the core
      engine for implementing a (near-) real-time digital surveillance system. A
      digital surveillance system that uses Internet resources has enormous potential
      to monitor disease outbreaks in the early phase.

PMID- 29181247
TI  - Interactive Visualization of Healthcare Data Using Tableau.
AB  - Objectives: Big data analysis is receiving increasing attention in many
      industries, including healthcare. Visualization plays an important role not only
      in intuitively showing the results of data analysis but also in the whole process
      of collecting, cleaning, analyzing, and sharing data. This paper presents a
      procedure for the interactive visualization and analysis of healthcare data using
      Tableau as a business intelligence tool. Methods: Starting with installation of
      the Tableau Desktop Personal version 10.3, this paper describes the process of
      understanding and visualizing healthcare data using an example. The example data
      of colon cancer patients were obtained from health insurance claims in years 2012
      and 2013, provided by the Health Insurance Review and Assessment Service.
      Results: To explore the visualization of healthcare data using Tableau for
      beginners, this paper describes the creation of a simple view for the average
      length of stay of colon cancer patients. Since Tableau provides various
      visualizations and customizations, the level of analysis can be increased with
      small multiples, view filtering, mark cards, and Tableau charts. Conclusions:
      Tableau is a software that can help users explore and understand their data by
      creating interactive visualizations. The software has the advantages that it can
      be used in conjunction with almost any database, and it is easy to use by
      dragging and dropping to create an interactive visualization expressing the
      desired format.

PMID- 29181248
TI  - EFFECT OF HEEL LIFTS ON PATELLOFEMORAL JOINT STRESS DURING RUNNING.
AB  - Background: Patellofemoral pain is a debilitating injury for many recreational
      runners. Excessive patellofemoral joint stress may be the underlying source of
      pain and interventions often focus on ways to reduce patellofemoral joint stress.
      Purpose: Heel lifts have been used as an intervention within Achilles tendon
      rehabilitation programs and to address leg length discrepancies. The purpose of
      this study was to examine the effect of running with heel lifts on patellofemoral
      joint stress, patellofemoral stress impulse, quadriceps force, step length,
      cadence, and other related kinematic and spatiotemporal variables. Study Design:
      A repeated-measures research design. Methods: Sixteen healthy female runners
      completed five running trials in a controlled laboratory setting with and without
      11mm heel lifts inserted in a standard running shoe. Kinetic and kinematic data
      were used in combination with a static optimization technique to estimate
      individual muscle forces. These data were inserted into a patellofemoral joint
      model which was used to estimate patellofemoral joint stress and other variables
      during running. Results: When running with heel lifts, peak patellofemoral joint
      stress and patellofemoral stress impulse were reduced by a 4.2% (p=0.049) and
      9.3% (p=0.002). Initial center of pressure was shifted anteriorly 9.1% when
      running with heel lifts (p<0.001) despite all runners utilizing a heel strike
      pattern. Dorsiflexion at initial contact was reduced 28% (p=0.016) when heel
      lifts were donned. No differences in step length and cadence (p>0.05) were shown
      between conditions. Conclusions: Heel lift use resulted in decreased
      patellofemoral joint stress and impulse without associated changes in step length
      or frequency, or other variables shown to influence patellofemoral joint stress.
      The center of pressure at initial contact was also more anterior using heel
      lifts. The use of heel lifts may have therapeutic benefits for runners with
      patellofemoral pain if the primary goal is to reduce patellofemoral joint stress.
      Level of Evidence: 3b.

PMID- 29181249
TI  - COMPARISON OF HAMSTRING MUSCLE ACTIVATION DURING HIGH-SPEED RUNNING AND VARIOUS
      HAMSTRING STRENGTHENING EXERCISES.
AB  - Purpose/Background: Several studies have examined the effect of hamstring
      strength exercises upon hamstring strains in team sports that involve many
      sprints. However, there has been no cross comparison among muscle activation of
      these hamstring training exercises with actual sprinting. Therefore, the aim of
      this study was to examine different hamstring exercises and compare the muscle
      activity in the hamstring muscle group during various exercises with the muscular
      activity produced during maximal sprints. Methods: Twelve male sports students
      (age 25 +/- 6.2 years, 1.80 +/- 7.1 m, body mass 81.1 +/- 15.6 kg) participated
      in this study. Surface EMG electrodes were placed on semimembranosus,
      semitendinosus and biceps femoris to measure muscle activity during seven
      hamstrings exercises and sprinting together with 3D motion capture to establish
      at what hip and knee angles maximal muscle activation (EMG) occurs. Maximal EMG
      activity during sprints for each muscle was used in order to express each
      exercise as a percentage of max activation during sprinting. Results: The main
      findings were that maximal EMG activity of the different hamstring exercises were
      on average between 40-65% (Semitendinosus), 18-40% (biceps femoris) and 40-75%
      (Semimembranosus) compared with the max EMG activity in sprints, which were
      considered as 100%. The laying kick together with the Nordic hamstring exercises
      and its variations had the highest muscle activations, while the cranes showed
      the lowest muscle activation (in all muscles) together with the standing kick for
      the semimembranosus. In addition, angles at which the peak EMG activity of the
      hamstring muscle occurs were similar for the Nordic hamstring exercises and
      different for the two crane exercises (hip angle), standing kick (hip angle) and
      the laying kick (knee angle) compared with the sprint. Conclusions: Nordic
      hamstring exercises with its variation together with the laying kick activates
      the hamstrings at high levels and at angles similar to the joint angles at which
      peak hamstring activation occurs during sprinting, while cranes did not reach
      high levels of hamstring activation compared with sprinting. Level of Evidence:
      1b.

PMID- 29181250
TI  - THE EFFICACY OF ANGLE-MATCHED ISOKINETIC KNEE FLEXOR AND EXTENSOR STRENGTH
      PARAMETERS IN PREDICTING AGILITY TEST PERFORMANCE.
AB  - Background: Agility is a fundamental performance element in many sports, but
      poses a high risk of injury. Hierarchical modelling has shown that eccentric
      hamstring strength is the primary determinant of agility performance. Purpose:
      The purpose of this study was to investigate the relationship between knee flexor
      and extensor strength parameters and a battery of agility tests. Study Design:
      Controlled laboratory study. Methods: Nineteen recreational intermittent games
      players completed an agility battery and isokinetic testing of the eccentric knee
      flexors (eccH) and concentric knee extensors (conQ) at 60, 180 and 300 degrees .s
      1. Peak torque and the angle at which peak torque occurred were calculated for
      eccH and conQ at each speed. Dynamic control ratios (eccH:conQ) and fast:slow
      ratios (300:60) were calculated using peak torque values, and again using angle
      matched data, for eccH and conQ. The agility test battery differentiated linear
      vs directional changes and prescriptive vs reactive tasks. Results: Linear
      regression showed that eccH parameters were generally a better predictor of
      agility performance than conQ parameters. Stepwise regression showed that only
      angle-matched strength ratios contributed to the prediction of each agility test.
      Trdaitionally calculated strength ratios using peak torque values failed to
      predict performance. Angle-matched strength parameters were able to account for
      80% of the variation in T-test performance, 70% of deceleration distance, 55% of
      10m sprint performance, and 44% of reactive change of direction speed.
      Conclusions: Traditionally calculated strength ratios failed to predict agility
      performance, whereas angle-matched strength ratios had better predictive ability
      and featured in a predictive stepwise model for each agility task. Level of
      Evidence: 2c.

PMID- 29181251
TI  - LOWER EXTREMITY KINEMATICS OF ACL-REPAIRED AND NON-INJURED FEMALES WHEN USING
      KNEE SAVERS(r).
AB  - Background: Knee Savers(r) (KS) are an ergonomic aid purported to lessen the risk
      of injuries linked to deep squats. While widely used in sports such as baseball
      and softball, KS have not been tested to determine their effect upon lower
      extremity kinematics in any population. Purpose: The purpose of the study was to
      determine if KS influenced the lower extremity kinematics when females with
      previous anterior cruciate ligament (ACL)-reconstruction and healthy participants
      completed an end-range squat. Study Design: A repeated measures, counter-balanced
      laboratory study design was used. Methods: Twenty female participants (mean (SD) 
      age: 21.65 (2.06) yrs, height: 175.26 (9.29) cm, weight: 64.66 (7.72) kg) with a
      history of ACL-repair (n=10) or non-injury (n=10) completed this study.
      Participants completed a standardized trial of three deep squats with and without
      KS. Movement was analyzed using 2D video analysis methods increasingly available
      in clinical environments. Results: During the ascending phases of a squatting
      motion, there was significantly greater medial (p = .009) and lateral (p = .005)
      motion of the patella in the frontal plane for non-injured participants, when
      compared to the ACL-repaired group. No significant differences were found in
      sagittal plane lower extremity kinematics when squatting with and without KS.
      Ascending angular velocity was slower in ACL-repaired than non-injured females (p
      = .008) and slower with the KS than without KS for non-injured females (p =
      .007). Conclusions: When squatting with and without KS, the non-injured group
      experienced more frontal plane motion at the knee, compared to the ACL-repaired
      group. However, while KS are purported to influence lower extremity joint
      positions during the bottom phase of a deep squat, the data from the current
      study did not support this claim. Additionally, KS appear to slow ascending
      velocity for those without a history of ACL-repair. These findings may have
      clinically meaningful implications for athletes who use KS during sport
      activities. Level of Evidence: Level 2.

PMID- 29181252
TI  - COMPARISON OF DRY NEEDLING VS. SHAM ON THE PERFORMANCE OF VERTICAL JUMP.
AB  - Introduction: Dry needling has been reported to decrease pain in subjects having
      myofascial trigger points, as well as pain in muscle and connective tissue.
      Objective: The purpose of the study was to compare the effects on the ability to
      perform a two-legged vertical jump between a group who received one bout of dry
      needling and a group who received one bout of a sham treatment. Methods: Thirty
      five healthy students (19 males, 16 females) were recruited to participate in
      this study (mean age 22.7+/- 2.4 years). The subjects were randomly divided into
      two groups- dry needling (n=18) vs sham (n=17). The dry needling group received
      needling to four sites on bilateral gastrocnemius muscles; two at the medial head
      and two at the lateral head. The sham group had the four areas of the
      gastrocnemius muscle pressed with the tube housing the needle, but the needle was
      never inserted into the skin. Two-legged vertical jump was measured with chalk
      marks on the wall before and after the dry needling and sham treatments. Results:
      Analysis with a t-test indicated that the dry needling group significantly
      increased vertical jump height 1.2 inches over the sham group. Conclusion: One
      bout of dry needling showed an immediate effect at significantly increasing
      vertical jump height in healthy, young adults. Future research is needed to
      determine if dry needling has any long-term effects. Level of Evidence: 2b.

PMID- 29181253
TI  - INTER-RATER RELIABILITY OF THE SELECTIVE FUNCTIONAL MOVEMENT ASSESSMENT (SFMA) BY
      SFMA CERTIFIED PHYSICAL THERAPISTS WITH SIMILAR CLINICAL AND RATING EXPERIENCE.
AB  - Background: The Selective Functional Movement Assessment (SFMA) assesses posture,
      muscle balance, and movement patterns in order to identify relevant
      musculoskeletal dysfunction in a clinical population. Purpose: The purposes of
      this study were to: (1) determine if raters with similar clinical experience and
      rating experience exhibit adequate agreement of the scoring for the SFMA during
      clinical use; (2) determine the reliability of the categorical scoring of the
      SFMA in a clinical population; (3) determine the reliability of the criterion
      checklist scoring of the SFMA in a clinical population; (4) compare the
      reliability of real-time assessment to recorded assessment. Design: Inter-rater
      reliability study. Methods: 49 clinical subjects (20.7 years +/- 1.6) were
      simultaneously assessed in real-time by two physical therapists and were recorded
      with digital video cameras in the sagittal and frontal view while they performed
      the fifteen component movement patterns that comprise the top-tier SFMA. The
      third physical therapist assessed the patterns from the video. Subjects were
      assessed using the SFMA categorical scoring and criterion checklist scoring
      tools. Results: The two live clinical raters demonstrated the greatest Cohen's
      Kappa scores (10 of 15) with moderate or better inter-rater agreement (Kappa >
      0.40) using the categorical scoring tool. The overall ICC [2,1] score indicated
      fair to moderate agreement between all raters for the criterion checklist scoring
      (ICC, SEM, p-value) (0.61, 8.23, p < 0.001). Real time clinical use was the most
      reliable method for using the criterion checklist scoring tool (0.72, 1.95,
      p=0.43). Conclusions: Using the categorical and criterion checklist tools in a
      clinical population to score the fifteen component fundamental movements of the
      SFMA demonstrated moderate or better reliability when performed clinically by
      certified SFMA raters. Level of Evidence: Reliability, Level 2.

PMID- 29181254
TI  - HIP RANGE OF MOTION IN RECREATIONAL WEIGHT TRAINING PARTICIPANTS: A DESCRIPTIVE
      REPORT.
AB  - Background: The surveillance of hip injuries and risk factors have become an
      emerging focus in sports medicine due to the increased recognition of hip
      pathologies. Researchers suggest that decreased hip range of motion (ROM) is a
      risk factor for injury in various athletic activities. One under reported
      population that has potential for hip injuries is recreational weight training
      (WT) participants. Currently, no studies have reported hip ROM values in WT
      participants which creates a knowledge gap in this population. Purpose: The
      purpose of this study was to report hip passive ROM values of WT participants to
      develop reference data for future research on injury patterns and prevention
      strategies for this population. Study Design: Descriptive cross sectional study.
      Methods: Two-hundred healthy recreational adult WT participants (age = 27.18 +/-
      9.3 years, height = 174.84 +/- 9.8 cm, mass = 91.0 +/- 17.9 kg, body mass index =
      29.6 +/- 4.5 kg/m2) were recruited. Bilateral hip passive ROM was assessed for
      flexion, extension, internal rotation, external rotation, and abduction.
      Statistical analysis included subject demographics (means and SD) and a two
      tailed independent t-test to compare mean passive hip ROM values between sexes
      and hips. Statistical significance was considered p < .05. Results: A total of
      400 hundred hips (right + left) were measured for this analysis. When comparing
      hip ROM values within sexes, men had no significant difference (p>=.28) between
      the right and left hip for all motions. Women did have a significant difference
      (p<=.05) between the right and left hip for all motions. The right hip had lower
      values for all motions than the left hip suggesting a more global decrease in
      right hip ROM. When comparing hip ROM values between men and women, there was a
      significant difference (p<=.05) between men and women for all motions. Men had
      lower ROM values for all hip motions when compared to women. Conclusion: This is
      the first investigation to provide a descriptive analysis of hip ROM in healthy
      recreational WT participants. These data provide a starting point for clinicians
      and researchers to further study this population for injury prevention. Evidence
      Level: 2.

PMID- 29181256
TI  - SPORTS PHYSICAL THERAPY CURRICULA IN PHYSICAL THERAPIST PROFESSIONAL DEGREE
      PROGRAMS.
AB  - Background: The specialty niche of sports physical therapy has grown at a
      significant rate over the past 40 years. Despite this growth there is little
      information or direction from the physical therapy education accreditation body
      or professional association to guide academic programs on the interest or
      necessity of this type of practice content in physical therapy professional
      degree programs. Purpose: The purpose of this survey study is to report on the
      prevalence, attitudes, barriers, resources, and faculty expertise in providing
      required or elective sports physical therapy course work. Study Design: Cross
      sectional descriptive survey. Methods: A 57-item questionnaire with branching
      logic was distributed via a web-based electronic data capture tool to survey all
      Commission on Accreditation for Physical Therapy Education (CAPTE) accredited and
      candidate schools in the United States. Response data was analyzed to describe
      typical educational program profiles, faculty demographics, and correlational
      factors consistent with the presence or absence of specific sports physical
      therapy curricular content. Results: Thirty one percent of the schools responded
      to the survey and the program demographics were consistent with all currently
      accredited schools in regards to their geography, Carnegie classification, and
      faculty and student size. Forty three percent of programs offered a required or
      elective course distinct to the practice of sports physical therapy. Descriptive
      information regarding the sequencing, curricular make-up, resources, and
      assessment of content competence is reported. The odds of providing this content
      nearly doubles for programs that have faculty with sports clinical specialist
      credentials, accredited sports residency curriculums, or state practice acts that
      allow sports venue coverage. Conclusions: This survey provides an initial
      overview of sports physical therapy educational efforts in professional physical
      therapy degree programs. The data can used to spur further discussion on the
      necessity, structure, and implementation of education content that is inherent to
      a growing specialty practice in the physical therapy profession. Level of
      Evidence: 4, Cross-sectional descriptive survey design.

PMID- 29181255
TI  - DEVELOPMENT OF A SCREENING PROTOCOL TO IDENTIFY INDIVIDUALS WITH DYSFUNCTIONAL
      BREATHING.
AB  - Introduction: Dysfunctional breathing (DB) has been linked to health conditions
      including low back pain and neck pain and adversely effects the musculoskeletal
      system. Individuals with DB often have decreased pain thresholds and impaired
      motor control, balance, and movement. No single test or screen identifies DB,
      which is multi-dimensional, and includes biochemical, biomechanical, and
      psychophysiological components. Several tools assess and test for DB, but no
      screen exists to determine whether additional testing and assessment are
      indicated. Purpose/Background: The purpose of this study was to develop a
      breathing screening procedure that could be utilized by fitness and healthcare
      providers to screen for the presence of disordered breathing. A diagnostic test
      study approach was utilized to establish the diagnostic accuracy of the newly
      developed screen for DB. Methods: A convenience sample of 51 subjects (27
      females, 27.0 years, BMI 23.3) were included. To test for DB related to the
      biochemical dimension, end-tidal CO2 (ETCO2) was measured with a capnography
      unit. To test for DB related to biomechanical dimension, the Hi-Lo test was
      utilized. To test for DB related to the psychophysiological dimension, the Self
      Evaluation of Breathing Symptoms Questionnaire (SEBQ) and Nijmegen questionnaires
      were utilized. Potential screening items that have been shown to be related to DB
      in previous research and that could be performed by non-health care personnel
      were utilized to create the index test including activity level, breath hold time
      (BHT), respiration rate, and the Functional Movement Screen (FMSTM). Results:
      There were no strong correlations between the three measures of DB. Five subjects
      had normal breathing, 14 failed at least one measure, 20 failed at least two, and
      12 failed all three. To develop screening items for each dimension, data were
      examined for association with failure. BHT and a four-item mini-questionnaire
      were identified as the most closely associated variables with failure of all
      three dimensions. A BHT of < 25 seconds and four questions were combined and
      yielded a sensitivity of 0.89 (0.85-0.93) and a specificity of 0.60 (0.18-0.92)
      for clinical identification of DB. Conclusion: Easily obtained clinical measures
      of BHT and four questions can be utilized to screen for the presence of DB. If
      the screen is passed, there is an 89% chance that DB is not present. If the
      screen is failed, further assessment is recommended. Level of Evidence: 2b.

PMID- 29181257
TI  - SHOULDER PAIN IN COMPETITIVE TEENAGE SWIMMERS AND IT'S PREVENTION: A
      RETROSPECTIVE EPIDEMIOLOGICAL CROSS SECTIONAL STUDY OF PREVALENCE.
AB  - Background: The term "swimmer's shoulder" was first introduced in 1974 by Kennedy
      and Hawkins to describe a common condition among competitive swimmers
      characterized by pain and dysfunction of the shoulder complex. Currently, the
      term does not define a specific clinical diagnosis and its etiology is considered
      to be multifactorial. In the literature shoulder pain prevalence varies according
      to the adopted definitions (from 3% to 91%); however, in the Italian environment
      there is no prevalence study regarding swimmer shoulder. Prevention by means of
      dry land activities may assist in delimiting shoulder pain in swimmers. Purposes:
      The purpose of this study was to investigate the prevalence of swimmer's shoulder
      over the prior 12 months among teenage athletes and the preventive activities
      carried out across different sport's teams. A second purpose was to determine
      whether the extent of the condition is affected by dry land preventive activity.
      And finally, to compare different preventive activities related to the prevalence
      of swimmer's shoulder. Study design: Retrospective epidemiological cross
      sectional study of prevalence. Methods: Athletes from four levels of training:
      Esordienti A, Ragazzi, Juniores and Cadetti (according to Italian Swimming
      Federation F.I.N.'s partition age) belonging to eight Italian swimming teams and
      their respective coaches were involved in this study. Two types of questionnaires
      were created and completed by both the athletes and their coaches during May
      2015. The collected data were analyzed by means of descriptive and inferential
      statistics. Results: Shoulder pain prevalence over the previous 12 months from
      the completion of the survey was 51%. In six out of eight of the societies a
      specific shoulder dry land warm-up was carried out before water training, whereas
      among seven out of eight societies also utilized weekly sessions of performance
      (physical) training. Statistically significant differences were noticed between
      shoulder pain and gender, weekly frequency and duration of dry land warm-up and
      duration of physical training. Conclusion: The results of the current study
      indicate that shoulder pain is prevalent in youth swimmers (51%) and appears to
      be affected by dry land preventive activities. A weekly frequency of dry land
      warm-up more than five times appeared to protect swimmers from pain (p=0.044);
      whereas, a dry land warm-up duration greater than 10 minutes seems to cause
      shoulder pain (p=0.043). A single physical training duration lower than 45
      minutes seems to be associated with pain (p=0.035). Levels of evidence: 3a.

PMID- 29181258
TI  - AGE DIFFERENCES IN MEASURES OF FUNCTIONAL MOVEMENT AND PERFORMANCE IN HIGHLY
      YOUTH BASKETBALL PLAYERS.
AB  - Background: There is a lack of information about the influence of age on
      functional movement tests (FMT) and performance tests as well as in their
      relationships in young basketball players. Purpose: The purpose of the present
      study was to determine the variations in FMT and jump and/or sprint performance
      scores between age groups (U-14 vs. U-16) in Highly-trained young basketball
      players. The second purpose was to investigate the relationship between FMT for
      lower body and jump and/or sprint performance in highly-trained young (U-14 and U
      16) male basketball players. Study Design: Descriptive study. Methods: Thirty
      elite young (U-14 to U-16) male basketball players performed several FMT (weight
      bearing dorsiflexion test [WB-DF] and a modified Star Excursion Balance test
      [SEBT]) and performance including unilateral and bilateral countermovement jumps,
      unilateral horizontal jumping, linear sprinting and performance tests. Results:
      All anthropometric and performance tests showed a statistically significant
      advantage (p<0.05) in the U-16 group, excluding the unilateral jump with left leg
      (p=0.127). Five out of the eight FMT performed showed a statistically significant
      advantage (p<0.05) in the U-16 group. The U-14 group did not differ statistically
      from the U-16 group in WB-DF with left leg and the SEBT anterior right leg and
      posteromedial left leg reaches. Effect size calculations did show small to
      moderate effects in favor of U-16. Only two significant correlations (p<0.05)
      between functional movement and performance measures were identified in the U-16
      group for either limb (10-m sprint and SEBT-PLL, SEBT-CompositeL), while a total
      of 13 significant correlations (p<0.05) in the U-14 group were found.
      Conclusions: The results of this study demonstrated differences in FMT and jump
      and/or sprint performance test between age groups (U-16 vs U-14). The findings of
      this study support the idea that the age of the player should be considered when
      interpreting FMT scores, which could have implications when implementing the FMT
      for injury risk prediction. Level of evidence: 2b.

PMID- 29181259
TI  - INJURY PATTERNS IN ADOLESCENT ELITE ENDURANCE ATHLETES PARTICIPATING IN RUNNING,
      ORIENTEERING, AND CROSS-COUNTRY SKIING.
AB  - Background: Prospective injury registration studies, monitoring adolescent elite
      athletes, are sparse in running, orienteering and cross-country skiing, yet
      essential for developing prevention programs. Purpose: The aims of this study
      were to describe the injury prevalence/incidence, severity grade, injury
      location, risk factors and the prevalence of illness in running (RU),
      orienteering (OR) and cross-country skiing athletes (CR). Study Design:
      Prospective cohort study. Methods: One hundred fifty adolescent elite athletes
      (age range 16-19), participating in orienteering (25 females, 20 males), running
      (13 females, 18 males), cross-country skiing (38 females, 36 males), from 12
      National Sports High Schools in Sweden, were prospectively followed over one
      calendar year using a reliable and validated web-based questionnaire. Results:
      The main finding was that the average weekly injury prevalence was higher during
      the pre-season compared to the competitive season in all three sports. RU
      reported the significantly (p<0.05) highest average weekly injury prevalence
      (32.4%) and substantial injury prevalence (17.0%), compared to OR (26.0, 8.2%)
      and CR (21.1%, 8.9%). Most injuries occurred in the lower extremity (RU 94.4%; OR
      91.9%; CR 49.9%) and foot and knee injuries had the highest severity grade in all
      three sports. History of serious injury (p=0.002, OR 4.0, 95% CI 1.6-9.7) and
      current injury at study start (p=0.004, OR 4.0, 95% CI 1.5-11.2) were identified
      as the strongest risk factors for substantial injury. Younger athletes aged 16
      (p=0.019, OR 2.6, 95% CI 1.2-5.8) and 17 (p=0.045, OR 2.4, 95% CI 1.0-5.9), had a
      significantly higher injury risk for substantial injury compared to older
      athletes aged 18-19. Conclusion: Practitioners should be aware of the increased
      injury risk during pre-season and in younger athletes. By focus on prevention of
      foot and knee injuries, the injuries with the highest severity grade will be
      targeted in adolescent elite athletes participating in running, orienteering and
      cross-country skiing. Level of evidence: 2b.

PMID- 29181260
TI  - INJURIES IN QUIDDITCH: A DESCRIPTIVE EPIDEMIOLOGICAL STUDY.
AB  - Background: Quidditch is a fast growing, physically intense, mixed-gender full
      contact sport. Originally adapted from Harry Potter novels, quidditch was first
      played in 2005 in the USA but is now played worldwide. It is essential to
      elucidate patterns of injury for the safety and growth of the sport of quidditch.
      It also provides a unique opportunity to study injury patterns in mixed-gender
      full-contact sport, an area of increasing importance with the developing culture
      of transition from single-gender to mixed-gender sports. Purpose: The purpose of
      this investigation was to examine the types of injuries sustained while playing
      quidditch in terms of their incidence, anatomical distribution and severity, and
      gender distribution. Methods: An anonymous self-reporting questionnaire was
      distributed to all active quidditch players in the UK. Data collection included
      player demographics, type of injury, mechanism of injury, player position,
      experience and treatment required, relating to the previous 12 months. Results: A
      total of 348 participants of 684 eligible athletes responded to the questionnaire
      representing a 50.87% response rate. There were 315 injuries reported by 180
      athletes in total, with an overall incidence of 4.06 injuries per 1,000 hours. A
      statistically significantly different rate of concussion was observed with female
      athletes sustaining more concussion than males (p=0.006). The overall rate of
      concussion was 0.651/1000hrs in males and 1.163/1000hrs in females (0.877/1000
      hours overall). Conclusions: This study provides the first quantitative
      description of injury rates in quidditch. The overall injury rates are no higher
      than those reported in other recreational contact sports. Female athletes were
      found to have a higher rate of concussion, which needs further investigation.
      These findings are relevant to players concerned about safety in quidditch and to
      governing bodies regarding governance of the sport. Level of Evidence: 3b.

PMID- 29181261
TI  - FUNCTIONAL OUTCOMES OF HIP ARTHROSCOPY IN AN ACTIVE DUTY MILITARY POPULATION
      UTILIZING A CRITERION-BASED EARLY WEIGHT BEARING PROGRESSION.
AB  - Introduction: Hip arthroscopy allows surgeons to address intra-articular
      pathology of the hip while avoiding more invasive open surgical dislocation.
      However the post-operative rehabilitation protocols have varied greatly in the
      literature, with many having prolonged periods of limited motion and weight
      bearing. Purpose: The purpose of this study was to describe a criterion-based
      early weight bearing protocol following hip arthroscopy and investigate
      functional outcomes in the subjects who were active duty military. Methods:
      Active duty personnel undergoing hip arthroscopy for symptomatic femoroacetabular
      impingement were prospectively assessed in a controlled environment for the
      ability to incorporate early postoperative weight-bearing with the following
      criteria: no increased pain complaint with weight bearing and normalized gait
      pattern. Modified Harris Hip (HHS) and Hip Outcome score (HOS) were performed
      preoperatively and at six months post-op. Participants were progressed with a
      standard hip arthroscopy protocol. Hip flexion was limited to not exceed 90
      degrees for the first three weeks post-op, with progression back to running
      beginning at three months. Final discharge was dependent upon the ability to run
      two miles at military specified pace and do a single leg broad jump within six
      inches of the contralateral leg without an increase in pain. Results: Eleven
      participants met inclusion criteria over the study period. Crutch use was
      discontinued at an average of five days following surgery based on established
      weight bearing criteria. Only one participant required continued crutch use at 15
      days. Participants' functional outcome was improved postoperatively, as
      demonstrated by significant increases in HOS and HHS. At the six month follow up,
      eight of 11 participants were able to take and complete a full Army Physical
      Fitness Test. Conclusions: Following completion of the early weight bearing
      rehabilitation protocol, 81% of participants were able to progress to full weight
      bearing by four days post-operative, with normalized pain-free gait patterns.
      Active duty personnel utilizing an early weight bearing protocol following hip
      arthroscopy demonstrated significant functional improvement at six months. Level
      of Evidence: Level 4, Case-series.

PMID- 29181262
TI  - EXERCISE, MANUAL THERAPY AND POSTURAL RE-EDUCATION FOR UNCONTROLLED EAR TWITCHING
      AND RELATED IMPAIRMENTS AFTER WHIPLASH INJURY: A CASE REPORT.
AB  - Background and Purpose: Whiplash Associated Disorders and the interventions used
      to remediate them are well documented in physical therapy literature. However,
      specific interventions for spasms of the neck musculature that also involve
      constant ear twitching have yet to be addressed. The purpose of this case report
      is twofold. First, to describe comprehensive physical therapy management and
      outcomes for a subject with uncontrolled ear twitching and related
      musculoskeletal impairments, and second, to discuss the physical therapist's
      approach to evidence-based care when faced with a paucity of literature
      addressing physical therapy interventions for subjects with uncontrolled ear
      twitching. Case Description: The subject was a 14-year-old female who sustained a
      right anterolateral whiplash injury when struck in the head by a volleyball seven
      months prior to physical therapy. Beginning five months after that injury, she
      experienced uncontrolled and constant superior/inferior movement of her right ear
      (hereafter described in this report as a twitch) in addition to facial and
      cervical pain from her initial injury. She was unable to participate in high
      school athletics due to her pain. A multimodal treatment approach including
      exercise, manual therapy, and postural reeducation was utilized during the
      subject's episode of care. Outcomes: After eight treatment sessions, the
      subjects's cervical range of motion and upper extremity strength improved. The
      reported frequency of ear twitching decreased, as did reports of neck and
      shoulder pain. In addition, her Neck Disability Index improved from a score of
      22, indicating moderate disability, to 9, indicating mild disability and she was
      able to return to sport activity. Discussion: With limited research to direct
      intervention, clinical reasoning was utilized to formulate an effective
      therapeutic intervention. A combination of manual therapy, exercise, and postural
      reeducation intervention was effective for this subject and could assist in
      guiding interventions for similarly unique clinical presentations in the future.
      Further research is needed to examine the etiology of ear twitching caused by
      muscle spasm and to develop additional evidence-based interventions for Whiplash
      Associated Disorders. Level of Evidence: Level 4.

PMID- 29181263
TI  - Cytogenetic study is not essential in patients with aplastic anemia.
AB  - Depending on contemporary treatment approach of aggressive immunosuppression,
      Aplastic Anemia (AA) is caused by immunological destruction of otherwise normal
      hematopoietic stem cells. The aim was to summarize the cytogenetic abnormalities
      in AA patients and the frequency of Fanconi Anemia (FA) in morphologically normal
      AA patients in eastern India. Ethical clearances were obtained from both
      institutions involved in this study. Out of 72800 patients attending the
      outpatient department, 520 pancytopenia patients were screened for AA after Bone
      marrow (BM) aspiration and biopsy. Samples were collected from 117 cases in 3
      phases. 51 peripheral venous blood (PVB) samples in the first phase, 19 BM & PVB
      paired samples in the second phase and 47 BM samples in third phase were
      collected followed by leukocyte and/or BM stem cell culture. Next GTG banding and
      karyotyping were performed. PVB was collected from 63 (< 50 years) AA patients
      and stress cytogenetics was done to diagnose FA. In the first phase of the study,
      out of 51 PVB samples, 1 (1.96%) showed a unique chromosomal abnormality, i.e.
      45,XY,rob(14:21)(p10:q10)[20]. In the second phase of study, among 19 BM & PVB
      paired samples, 1 (5.26%) showed abnormal karyotype i.e. 45,X,-Y[3]/46,XY[47]. In
      the third phase of the study, 47 BM samples showed normal karyotype. Only 6
      (9.52%) cases were found positive for stress cytogenetics. A negligible
      percentage showing cytogenetic abnormality in such a considerable number of AA
      cases indicates that routine cytogenetic analysis of AA patient is not essential.
      A significant percentage was positive for stress cytogenetics; suggestive for FA,
      even the patients were morphologically normal.

PMID- 29181265
TI  - Off label use of direct oral anticoagulants for left ventricular thrombus. Is it
      appropriate?
AB  - A 57 year old gentleman with a history of non-ischemic cardiomyopathy and
      paroxysmal atrial fibrillation presented with worsening lower extremity edema and
      dyspnea on exertion. He had been compliant with his medications including
      rivaroxaban (Xarelto) for atrial fibrillation that he takes with the evening meal
      daily. His echocardiogram showed an ejection fraction of 10-15% and a new left
      ventricle (LV) apical thrombus. During his hospital stay, he developed right
      sided weakness. Magnetic Resonance Imaging showed a subacute infarct involving
      the left parietal lobe. The decision was made to discontinue rivaroxaban and
      initiate heparin infusion instead. Meanwhile, the patient's neurological symptoms
      were closely monitored. The patient was then transitioned to warfarin. He was
      eventually transferred to the rehabilitation floor with minimal residual
      neurologic weakness. Left ventricular thrombus is an important complication in
      the setting of systolic dysfunction. The combination of blood stasis, endothelial
      injury and hypercoagulability, is a prerequisite for in-vivo thrombus formation.
      The slow onset of action and reversal, need for frequent monitoring, narrow
      therapeutic range, dietary restrictions, and multiple drug interactions limit the
      use of vitamin K antagonists. Direct-acting oral anticoagulants (DOACs) do not
      have these limitations and may also reduce the risk of hemorrhagic stroke. Our
      patient developed an LV thrombus while on uninterrupted DOAC therapy.

PMID- 29181264
TI  - Evaluation of bone mineral density and related parameters in patients with
      haemophilia: a single center cross-sectional study.
AB  - Haemophilia has been associated with low bone mineral density (BMD) probably due
      to some predisposing factors. The aim of this study was to evaluate the
      relationship between BMD and potential clinical predictors in adult haemophilic
      patients. Fortynine patients with moderate and severe haemophilia were enrolled.
      BMD was measured by Dual Energy X-Ray Absorptiometry (DXA) and blood tests were
      performed for vitamin D, calcium, phosphore, alkaline phosphatase and
      parathormone levels. Functional Independence Score in Haemophilia (FISH) and
      Haemophilia Joint Health Score (HJHS) were used to assess musculoskeletal
      functions. Body mass index (BMI), Hepatitis C virus (HCV)/Human immunodeficiency
      virus (HIV) seropositivity and smoking status were also recorded. BMD was found
      lower than expected for reference age in 34.8% of patients of less than 50 years
      old. In patients older than 50 years, 66.6% of them had osteoporosis and 33.3% of
      them had normal BMD. FISH score was statistically significant correlated with BMD
      of total hip (TH) and femur neck (FN) but not with lumbar spine (LS). In eligible
      patients, there was also a statistically significant correlation between BMD of
      TH and HJHS. Vitamine D deficiency was common and found in 77.5% of patients,
      although there was no significant correlation with BMD. Also no correlation was
      found between BMD and blood tests, HCV/HIV status, BMI and smoking. This study
      confirmed that patients with haemophilia have an increased prevelance of low BMD
      even in younger group. Our results showed that there are significant correlations
      between FISH score and BMD of TH and FN and also between HJHS score and BMD of
      TH. Thus, using scoring systems may be beneficial as a simple predictors of BMD
      to reflect the severity of haemophilic arthropathy.

PMID- 29181266
TI  - Gender differences in ST-elevation myocardial infarction (STEMI) time delays:
      experience of a public health service in Salvador-Brazil.
AB  - BACKGROUND: Delays in attending to ST-elevation myocardial infarction (STEMI) are
      indicators or markers of quality of health services. Several records suggest
      gender disparity in cardiac care as a contributor to the increased mortality
      among women. METHODS: We prospectively enrolled all consecutive STEMI patients
      who were transferred to our hospital from January through December 2015. The
      following variables were analyzed: Symptom-to-Door Time (SDT); Time to First ECG
      (TECG); Transfer Time to Referring Center (TTRC); and Door-to-Cath lab time
      (DCT). RESULTS: Of the 133 patients, 85 (63.9%) were male and 45 (36%) female.
      The mean age and body mass index (BMI) between the male and female genders were
      56.3 and 60.5 years for the first and 26 and 27.7 Kg/M2 for the second. Diabetes
      and low school education level were more prevalent in women than men, with
      statistical significance: 20 (48.8%) vs 18 (26.1%) with P = 0.01 and 26 (54.2%)
      vs 28 (32.9%) with P = 0.04, respectively. Regarding the times evaluated (SDT,
      TECG, TTRC and DCT), there was no statistically significant difference in
      relation to gender. STEMI Killip class I was more prevalent in males: 93 (86.1%)
      vs 12 (63.2%) cases with P = 0.01, and thrombolysis with a tendency towards the
      same direction: 17 (20%) vs 4 (8.3%) and P = 0.07. CONCLUSIONS: According to our
      results women with STEMI had significantly higher prevalence of diabetes and low
      school education level, as well as a higher proportion of complicated STEMI
      (Killip class >= II).

PMID- 29181267
TI  - Variation and repeatability of measured standardized uptake values depending on
      actual values: a phantom study.
AB  - Standardized uptake values (SUVs) are the most widely used quantitative imaging
      biomarkers in positron emission tomography (PET); however, little is known about
      the changes in variation and repeatability of SUVs depending on the magnitude of
      the values. We hypothesized that low SUVs have larger variations than high SUVs,
      and attempted various kinds of experimental PET scans using a phantom. By
      adjusting the ratio of F-18 solution to tap water, a NEMA IEC body phantom was
      set for SUVs of 2.0, 4.0, and 8.0 inside six hot spheres. PET data were obtained
      for 4 hours, and the data reconstructed every 2 min. The SUVmax and SUVpeak of
      the spheres in all images were recorded. The relative SUVs were calculated by
      dividing the measured SUV by actual SUV, and used for the Bland-Altman plots.
      Some variation was observed for the measured SUVs. The measured SUVs for the
      actual SUV of 2.0 showed the largest variation among those of 2.0, 4.0, and 8.0,
      and those of 8.0 showed the smallest. Similarly, the relative SUVs showed
      significantly larger variations for lower values. In addition, the relative
      SUVmax showed larger variation and value than the relative SUVpeak. The Bland
      Altman plots showed considerable variation and little agreement, but the degree
      of variation decreased as the measured value increased. We demonstrated some
      variation of the measured SUVs, which decreased for larger measured values.
      Clinicians should consider the inaccuracy of low SUVs not only in daily practice,
      but also for multi-institutional studies.

PMID- 29181268
TI  - The flip-flop fungus sign: an FDG PET/CT sign of benignity.
AB  - Benign granulomatous processes such as fungal infection may mimic metastatic lung
      cancer on FDG PET/CT. We found that these processes often have draining lymph
      node(s) with equal or greater FDG activity than associated lung nodule(s), a
      "flip-flop" of what is commonly seen in lung cancer. The aim of this study was to
      examine the utility of this "flip-flop fungus" (FFF) sign for diagnosing benign
      pulmonary disease. FDG PET/CT scans performed between 9/09-3/13 for the
      indications of pulmonary nodule or mass were reviewed. Scans with at least one
      hilar or mediastinal FDG avid draining node were included. Patients with a
      history of cancer, lack of pathologic confirmation, or without at least two years
      of imaging follow-up were excluded. A total of 209 FDG PET/CT exams were included
      and reviewed in a blinded fashion. A positive FFF sign had a sensitivity of 60.0%
      (95% CI: 47.6-71.5%) and specificity of 84.9% (95% CI: 77.8-90.4%) (P<0.0001) for
      benign disease. With additional strict imaging criteria applied, the FFF sign had
      a specificity of 98.6% (95% CI: 94.9-99.8%) (P<0.0001) and a positive predictive
      value of 90.0% (95% CI: 68.3-98.5%). A positive FFF sign was predominately due to
      granulomatous disease (91%), mostly histoplasmosis (73%). A positive FFF sign
      combined with positive fungal serology (n=16) had a specificity of 100% for
      benign disease. The FFF sign predicts benign disease in patients with a lung
      nodule(s) and an FDG avid draining lymph node(s) that would otherwise be
      considered worrisome for cancer.

PMID- 29181269
TI  - Diagnostic test accuracy study of 18F-sodium fluoride PET/CT, 99mTc-labelled
      diphosphonate SPECT/CT, and planar bone scintigraphy for diagnosis of bone
      metastases in newly diagnosed, high-risk prostate cancer.
AB  - The aim of this study was to prospectively compare planar, bone scan (BS) versus
      SPECT/CT and NaF PET/CT in detecting bone metastases in prostate cancer. Thirty
      seven consecutive, newly diagnosed, prostate cancer patients with prostate
      specific antigen (PSA) levels >= 50 ng/mL and who were considered eligible for
      androgen-deprivation therapy (ADT) were included in this study. BS, SPECT/CT, and
      NaF PET/CT, were performed prior to treatment and were repeated after six months
      of ADT. Baseline images from each index test were independently read by two
      experienced readers. The reference standard was based on a consensus decision
      made by a multidisciplinary team on the basis of baseline and follow-up images of
      the index tests, the findings of the baseline index tests by the experienced
      readers, and any available imaging, biochemical, and clinical data, including the
      response to ADT. Twenty-seven (73%) of the 37 patients had bone metastases
      according to the reference standard. The sensitivities for BS, SPECT/CT and NaF
      PET/CT were 78%, 89%, and 89%, respectively, and the specificities were 90%,
      100%, and 90%, respectively. The positive predictive values of BS, SPECT/CT and
      NaF PET/CT were 96%, 100%, and 96%, respectively, and the negative predictive
      values were 60%, 77% and 75%, respectively. No statistically significant
      difference among the three imaging modalities was observed. All three imaging
      modalities showed high sensitivity and specificity. NaF PET/CT and SPECT/CT
      showed numerically improved, but not statistically superior, sensitivity compared
      with BS in this limited and selected patient cohort.

PMID- 29181270
TI  - Safety and accuracy of 68Ga-DOTATOC PET/CT in children and young adults with
      solid tumors.
AB  - 68Ga-DOTA-tyr3-Octreotide (68Ga-DOTATOC) PET/CT has been shown to have high
      accuracy in adults with neuroendocrine tumors, however has not been studied in
      pediatric patients. This study evaluated the safety and accuracy of 68Ga-DOTATOC
      PET/CT in children and young adults with solid tumors that express somatostatin
      receptor type 2. A series of three prospective, IRB approved, clinical trials
      evaluating safety and efficacy of 68Ga-DOTATOC PET/CT were conducted for subjects
      aged 6 months to 90 years. This study reports the results for the 26 children and
      young adults, aged 16 months to 29 years who participated in these trials. The
      administered activity of 68Ga-DOTATOC was 1.59 MBq/kg with an upper limit of 111
      MBq for subjects < 18 years and 148 MBq for young adults. Safety was assessed
      with laboratory studies and patient/parent report of symptoms before and after
      the scan. Scans were interpreted in consensus by two board-certified nuclear
      medicine physicians. Each scan was categorized on a patient basis as true
      positive, true negative, false negative or false positive against a reference
      standard that included a combination of histopathology, other imaging modalities
      and clinical follow-up. Nine Grade I adverse events (AEs) occurred among 26
      subjects, none of which were attributable to 68Ga-DOTATOC. Sensitivity of 68Ga
      DOTATOC PET/CT was 88% (14 true positive, 2 false negative) and specificity was
      100% (10 true negative, 0 false positive). 68Ga-DOTATOC PET/CT is safe and
      accurate in children and young adults with solid tumors expressing somatostatin
      receptor type 2.

PMID- 29181271
TI  - Radium-223 IN metastatic hormone-sensitive high-grade prostate cancer: initial
      experience.
AB  - Our study evaluates the feasibility of compassionate exemption of Radium-223
      (223Ra) treatment in metastatic hormone-sensitive high-grade prostate cancer
      (mHSHGPC) patients with concomitant androgen deprivation-therapy (ADT). Seven
      patients with mHSHGPC, were treated with six cycles of 223Ra plus ADT. All
      patients had undergone to 18F-NaF-PET/CT. A qualitative analyses of the 18F-NaF
      PET/CT was performed in conjunction with Alkaline Phosphatase (ALP), Lactate
      dehydrogenase (LDH) and Prostatic-Specific Antigen (PSA) values. The mean of
      SUVmax values were used as a quantitative measure of tumoral burden. Changes in
      PSA, ALP, LDH from baseline were evaluated, and were defined as increase or
      decrease of at least 30%. Clinical response was achieved if there was pain
      reduction using visual analogic scale. Four patients showed a significant
      reduction in mean SUVmax after 3 cycles of 223Ra, and one after 6 cycles.
      Patients who showed reductions in mean SUVmax after Ra-223 also showed reductions
      in PSA, ALP and LDH. Four weeks after the last cycle of 223Ra all patients had
      decreased total PSA, ALP and LDH values >= 30% also significant improvement on
      pain. No progress disease was documented after 14 +/- 4 weeks. We found slight to
      moderate decreases in neutrophils and hemoglobin in two patients. We concluded
      that 223Ra plus ADT can be useful in mHSHGPC; the semi-quantitative 18F-NaF
      PET/CT as a method effective to monitor the treatment response. Due to
      concomitant administration of ADT, 18F-NaF-PET/CT cannot differentiate whether
      the findings were due to androgen blockade or the 223Ra; nevertheless, data
      supporting the efficacy of 223Ra is the significant improvement on pain.

PMID- 29181272
TI  - New insights in the use of immunoglobulins for the management of immune
      deficiency (PID) patients.
AB  - Immunoglobulin replacement therapy (IRT) is standard treatment for patients with
      primary immunodeficiency (PID). Because most of the patients with PID will
      require long life-time immunoglobulin replacement therapy, the quality of the
      prescribed products is of utmost importance. The IRT is generally administered
      either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG).
      Both routes have been demonstrated to be effective. The preferred route may vary
      at different times during a given patient's life. Options are therefore not fixed
      and the choice of route for immunoglobulin therapy will depend on several
      factors, including patient characteristics, clinical indication, venous access,
      side effects, rural or remote location, treatment compliance and patient
      preference. Many years ago, immunoglobulin therapy was associated with side
      effects which may compromise patient's compliance and quality of life of the
      patients. Most of the side effects were related to impurities. Recently, major
      advances in the manufacturing process have been made and new processes, such as
      the Quality by design (QbD) approach were added into the manufacturing steps to
      ensure patients tolerability and safety. Due to the improved purity of the
      immunoglobulin products obtained by these processes, the incidence of side
      effects is lower, while the ways of administration of Ig therapy and the choice
      of the regimen has widened to suit patient's preference and needs.

PMID- 29181273
TI  - Optimizing peptide epitope-based autoantibody detection in cancer patients.
AB  - Autoantibody (autoAb) response is an important arm of endogenously arising anti
      tumor immune responses, and has received new attention as a cancer biomarker with
      the recent success of immune check-point inhibitor therapy. Our laboratory has
      been focusing on measuring autoAb against B-cell epitopes in order to bypass the
      necessity to purify a panel of recombinant proteins. In order to optimize peptide
      based autoAb measurement and to increase sensitivities to cover more patients, we
      developed a new approach of using mixed peptides to conjugate on the same
      microsphere and compared its results with the use of a dominant peptide epitope
      using Luminex microbead-based multiplex assays. The peptide epitopes of two
      cancer/germline antigens, New York esophageal cancer antigen-1 (NY-ESO-1) and X
      antigen family member-1b (XAGE-1b), and cancer/stem cell antigen, sex determining
      region Y-box-2 (SOX2), were used as prototypes in this study. Our results
      indicate that using mixed peptides of B-cell epitopes improves the sensitivity of
      detecting more patients with autoAb responses. Thus, when the full-length protein
      is not available for conjugating onto microspheres, a mixture of B-cell epitopes
      is the method of choice for using Luminex multiplex assay to detect autoAb
      response in cancer patients.

PMID- 29181274
TI  - Assessment of brain functional connectome alternations and correlation with
      depression and anxiety in major depressive disorders.
AB  - Major depressive disorder (MDD) is highly prevalent, recurrent, and associated
      with functional impairment, morbidity, and mortality. Herein, we aimed to
      identify disruptions in functional connectomics among subjects with MDD by using
      resting-state functional magnetic resonance imaging (rs-fMRI). Sixteen subjects
      with MDD and thirty health controls completed resting-state fMRI scans and
      clinical assessments (e.g., Hamilton Depression Rating Scale (HAMD) and Hospital
      Anxiety and Depression Scale (HADS)). We found higher amplitude of low frequency
      fluctuations (ALFF) bilaterally in the hippocampus and amygdala among MDD
      subjects when compared to healthy controls. Using graph theoretical analysis, we
      found decreased clustering coefficient, local efficiency, and transitivity in the
      MDD patients. Our findings suggest a potential biomarker for differentiating
      individuals with MDD from individuals without MDD.

PMID- 29181275
TI  - Morphological and molecular data confirm the transfer of homostylous species in
      the typically distylous genus Galianthe (Rubiaceae), and the description of the
      new species Galianthe vasquezii from Peru and Colombia.
AB  - Galianthe (Rubiaceae) is a neotropical genus comprising 50 species divided into
      two subgenera, Galianthe subgen. Galianthe, with 39 species and Galianthe subgen.
      Ebelia, with 11 species. The diagnostic features of the genus are: usually erect
      habit with xylopodium, distylous flowers arranged in lax thyrsoid inflorescences,
      bifid stigmas, 2-carpellate and longitudinally dehiscent fruits, with dehiscent
      valves or indehiscent mericarps, plump seeds or complanate with a wing-like
      strophiole, and pollen with double reticulum, rarely with a simple reticulum.
      This study focused on two species that were originally described under Diodia due
      to the occurrence of fruits indehiscent mericarps: Diodia palustris and D.
      spicata. In the present study, classical taxonomy is combined with molecular
      analyses. As a result, we propose that both Diodia species belong to Galianthe
      subgen. Ebelia. The molecular position within Galianthe, based on ITS and ETS
      sequences, has been supported by the following morphological characters:
      thyrsoid, spiciform or cymoidal inflorescences, bifid stigmas, pollen grains with
      a double reticulum, and indehiscent mericarps. However, both species, unlike the
      remainder of the genus Galianthe, have homostylous flowers, so the presence of
      this type of flower significantly modifies the generic concept. In this
      framework, a third homostylous species, Galianthe vasquezii, from the Andean
      region is also described. Until now, this species remained cryptic under
      specimens of Galianthe palustris It differs however from the latter by having
      longer calyx lobes, the presence of dispersed trichomes inside the corolla lobes
      (vs. glabrous), fruits that are acropetally dehiscent (vs. basipetally
      dehiscent), and its Andean geographical distribution (vs. Paranaense).
      Additionally, a lectotype has been chosen for Diodia palustris, Borreria
      pterophora has been placed under synonymy of Galianthe palustris, and Galianthe
      boliviana is reported for the first time from Peru. A key of all Galianthe
      species with indehiscent mericarps is also provided.

PMID- 29181276
TI  - I-ATAC: interactive pipeline for the management and pre-processing of ATAC-seq
      samples.
AB  - Assay for Transposase Accessible Chromatin (ATAC-seq) is an open chromatin
      profiling assay that is adapted to interrogate chromatin accessibility from small
      cell numbers. ATAC-seq surmounted a major technical barrier and enabled epigenome
      profiling of clinical samples. With this advancement in technology, we are now
      accumulating ATAC-seq samples from clinical samples at an unprecedented rate.
      These epigenomic profiles hold the key to uncovering how transcriptional programs
      are established in diverse human cells and are disrupted by genetic or
      environmental factors. Thus, the barrier to deriving important clinical insights
      from clinical epigenomic samples is no longer one of data generation but of data
      analysis. Specifically, we are still missing easy-to-use software tools that will
      enable non-computational scientists to analyze their own ATAC-seq samples. To
      facilitate systematic pre-processing and management of ATAC-seq samples, we
      developed an interactive, cross-platform, user-friendly and customized desktop
      application: interactive-ATAC (I-ATAC). I-ATAC integrates command-line data
      processing tools (FASTQC, Trimmomatic, BWA, Picard,
      ATAC_BAM_shiftrt_gappedAlign.pl, Bedtools and Macs2) into an easy-to-use platform
      with user interface to automatically pre-process ATAC-seq samples with
      parallelized and customizable pipelines. Its performance has been tested using
      public ATAC-seq datasets in GM12878 and CD4+T cells and a feature-based
      comparison is performed with some available interactive LIMS (Galaxy, SMITH,
      SeqBench, Wasp, NG6, openBIS). I-ATAC is designed to empower non-computational
      scientists to process their own datasets and to break to exclusivity of data
      analyses to computational scientists. Additionally, I-ATAC is capable of
      processing WGS and ChIP-seq samples, and can be customized by the user for one
      independent or multiple-sequential operations.

PMID- 29181277
TI  - Antibodies to Bordetella pertussis antigens in maternal and cord blood pairs: a
      Thai cohort study.
AB  - Background: Pertussis is a vaccine-preventable disease, yet an increasing
      incidence of pertussis occurs in many countries. Thailand has a long-standing
      pertussis vaccination policy, therefore most expectant mothers today had received
      vaccines as children. The resurgence of pertussis among Thai infants in recent
      years led us to examine the pre-existing antibodies to Bordetella pertussis
      antigens in a cohort of 90 pregnant women. Methods: We evaluated the IgG to the
      Pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) in
      maternal and cord blood sera using commercial enzyme-linked immunosorbent assays
      (ELISA). Results: When values of >10 IU/ml were accepted as potential protective
      concentrations, we found that the percentages of unprotected infants were 73.3%,
      43.3% and 75.5% for anti-PT, anti-FHA and anti-PRN IgG, respectively. Discussion:
      These results may explain the susceptibility for pertussis among newborn infants
      in Thailand and support the requirement for a pertussis booster vaccine during
      pregnancy, which may contribute to the passive seroprotection among newborns
      during the first months of life.

PMID- 29181280
TI  - Associations of IGF2 and DRD2 polymorphisms with laying traits in Muscovy duck.
AB  - Insulin-like growth factor 2 (IGF2) and dopamine receptor 2 (DRD2) play important
      roles in ovarian follicular development. In this study, we analyzed tissue
      specific expression of the Muscovy duck IGF2 and DRD2 genes and cloned those
      genes transcripts. Polymorphisms in these genes were tightly linked with egg
      production traits and both genes were highly expressed in the ovary. Moreover, we
      identified five single nucleotide polymorphisms (SNPs) for IGF1 and 28 for DRD2.
      Mutations A-1864G and C-1704G of IGF2 were positively correlated with increased
      egg laying at 59 weeks (E59W) (P < 0.05). The C+7T and C+364G mutations of DRD2
      were highly and significantly associated with first-egg age (FEA) and egg numbers
      at 300 days (E300D) (P < 0.01). Moreover, C+3301G and C+3545G of DRD2 were highly
      significantly associated with FEA, E59W and E300D (P < 0.01). Other mutations
      were positively associated with FEA or E300D or E59W (P < 0.05). These data
      suggest specific roles for IGF1 and DRD2 polymorphisms in egg production in
      Muscovy ducks.

PMID- 29181281
TI  - Do rotational shear-cushioning shoes influence horizontal ground reaction forces
      and perceived comfort during basketball cutting maneuvers?
AB  - Background: Court shoe designs predominantly focus on reducing excessive vertical
      ground reaction force, but shear force cushioning has received little attention
      in the basketball population. We aimed to examine the effect of a novel shoe
      cushioning design on both resultant horizontal ground reaction forces and comfort
      perception during two basketball-specific cutting movements. Methods: Fifteen
      university team basketball players performed lateral shuffling and 45-degree
      sidestep cutting at maximum effort in basketball shoes with and without the shear
      cushioning system (SCS). Paired t-tests were used to examine the differences in
      kinetics and comfort perception between two shoes. Results: SCS shoe allowed for
      larger rotational material deformation compared with control shoes, but no
      significant shoe differences were found in braking phase kinetics during both
      cutting movements (P = 0.35). Interestingly, a greater horizontal propulsion
      impulse was found with the SCS during 45-degree cutting (P < 0.05), when compared
      with the control. In addition, players wearing SCS shoes perceived better
      forefoot comfort (P = 0.012). During lateral shuffling, there were no significant
      differences in horizontal GRF and comfort perception between shoe conditions (P >
      0.05). Discussion: The application of a rotational shear-cushioning structure
      allowed for better forefoot comfort and enhanced propulsion performance in
      cutting, but did not influence the shear impact. Understanding horizontal ground
      reaction force information may be useful in designing footwear to prevent shear
      related injuries in sport populations.

PMID- 29181279
TI  - Genome-wide survey of single-nucleotide polymorphisms reveals fine-scale
      population structure and signs of selection in the threatened Caribbean elkhorn
      coral, Acropora palmata.
AB  - The advent of next-generation sequencing tools has made it possible to conduct
      fine-scale surveys of population differentiation and genome-wide scans for
      signatures of selection in non-model organisms. Such surveys are of particular
      importance in sharply declining coral species, since knowledge of population
      boundaries and signs of local adaptation can inform restoration and conservation
      efforts. Here, we use genome-wide surveys of single-nucleotide polymorphisms in
      the threatened Caribbean elkhorn coral, Acropora palmata, to reveal fine-scale
      population structure and infer the major barrier to gene flow that separates the
      eastern and western Caribbean populations between the Bahamas and Puerto Rico.
      The exact location of this break had been subject to discussion because two
      previous studies based on microsatellite data had come to differing conclusions.
      We investigate this contradiction by analyzing an extended set of 11
      microsatellite markers including the five previously employed and discovered that
      one of the original microsatellite loci is apparently under selection. Exclusion
      of this locus reconciles the results from the SNP and the microsatellite
      datasets. Scans for outlier loci in the SNP data detected 13 candidate loci under
      positive selection, however there was no correlation between available
      environmental parameters and genetic distance. Together, these results suggest
      that reef restoration efforts should use local sources and utilize existing
      functional variation among geographic regions in ex situ crossing experiments to
      improve stress resistance of this species.

PMID- 29181282
TI  - Modus operandi and affect in Sweden: the Swedish version of the Regulatory Mode
      Questionnaire.
AB  - Background: The Regulatory Mode Questionnaire (RMQ) is the most used and
      internationally well-known instrument for the measurement of individual
      differences in the two self-regulatory modes: locomotion (i.e., the aspect of
      self-regulation that is concerned with movement from state to state) and
      assessment (i.e., the comparative aspect of self-regulation). The aim of the
      present study was to verify the independence of the two regulatory modes, as
      postulated by the Regulatory Mode Theory (Kruglanski et al., 2000), and the
      psychometric properties of the RMQ in the Swedish context. Furthermore, we
      investigated the relationship between regulatory modes (locomotion and
      assessment) and affective well-being (i.e., positive affect and negative affect).
      Method: A total of 655 university and high school students in the West of Sweden
      (males = 408 females = 242, and five participants who didn't report their gender;
      agemean = 21.93 +/- 6.51) responded to the RMQ and the Positive Affect Negative
      Affect Schedule. We conducted two confirmatory factor analyses using structural
      equation modeling (SEM). A third SEM was conducted to test the relationship
      between locomotion and assessment to positive affect and negative affect.
      Results: The first analyses confirmed the unidimensional factor structure of
      locomotion and assessment and both scales showed good reliability. The assessment
      scale, however, was modified by dropping item 10 ("I don't spend much time
      thinking about ways others could improve themselves".) because it showed low
      loading (.07, p = .115). Furthermore, the effect of locomotion on positive affect
      was stronger than the effect of assessment on positive affect (Z = -15.16, p <
      .001), while the effect of assessment on negative affect was stronger than the
      effect of locomotion on negative affect (Z = 10.73, p < .001). Conclusion: The
      factor structure of the Swedish version of the RMQ is, as Regulatory Mode Theory
      suggests, unidimensional and it showed good reliability. The scales discriminated
      between the two affective well-being dimensions. We suggest that the Swedish
      version of the RMQ, with only minor modifications, is a useful instrument to tap
      individual differences in locomotion and assessment. Hence, the present study
      contributes to the validation of the RMQ in the Swedish culture and adds support
      to the theoretical framework of self-regulatory mode.

PMID- 29181283
TI  - Hydrothermal synthesis of ZnO quantum dot/KNb3O8 nanosheet photocatalysts for
      reducing carbon dioxide to methanol.
AB  - ZnO quantum dots and KNb3O8 nanosheets were synthesized by a two-step
      hydrothermal method for the photocatalytic reduction of CO2 to methanol where
      isopropanol is simultaneously oxidized to acetone . The as-prepared
      photocatalysts were characterized by X-ray diffraction (XRD), energy dispersive X
      ray spectroscopy (EDS), scanning electron microscopy (SEM), high-resolution
      transmission electron microscopy (HRTEM) and UV-vis absorption spectroscopy (UV
      vis). The photocatalytic activity of the materials was evaluated by formation
      rate of methanol under UV light irradiation at ambient temperature and pressure.
      The methanol formation rate of pure KNb3O8 nanosheets was found to be 1257.21
      MUmol/g/h, and after deposition of 2 wt % ZnO quantum dots on the surface of
      KNb3O8 nanosheets, the methanol production rate was found to increase to 1539.77
      MUmol/g/h. Thus, the ZnO quantum dots obviously prompted separation of charge
      carriers, which was explained by a proposed mechanism for this photocatalytic
      reaction.

PMID- 29181278
TI  - An update on anticancer drug development and delivery targeting carbonic
      anhydrase IX.
AB  - The expression of carbonic anhydrase (CA) IX is up-regulated in many types of
      solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of
      CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes
      has been shown to reverse the acidic environment of solid tumors and reduce the
      tumor growth establishing the significant role of CA IX in tumorigenesis. Thus,
      the development of potent antitumor drugs targeting CA IX with minimal toxic
      effects is important for the target-specific tumor therapy. Recently, several
      promising antitumor agents against CA IX have been developed to treat certain
      types of cancers in combination with radiation and chemotherapy. Here we review
      the inhibition of CA IX by small molecule compounds and monoclonal antibodies.
      The methods of enzymatic assays, biophysical methods, animal models including
      zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect
      hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to
      overview the recent progress related to novel therapeutic agents that target CA
      IX in hypoxic tumors.

PMID- 29181284
TI  - Fabrication of gold-coated PDMS surfaces with arrayed triangular
      micro/nanopyramids for use as SERS substrates.
AB  - Using the tip-based continuous indentation process, arrays of three-dimensional
      pyramidal cavities have been successfully machined on a copper template and the
      structures were successfully transferred to a polydimethylsiloxane (PDMS) surface
      using a reverse nanoimprinting approach. The structured PDMS surface is coated
      with a thin Au film, and the final substrate is demonstrated as a surface
      enhanced Raman spectroscopy (SERS) substrate. Rhodamine 6G (R6G) was used as a
      probe molecule in the present study to confirm the SERS measurements. Arrays of
      micro/nanostructures of different dimensions were formed by the overlap of
      pyramidal cavities with different adjacent distances using the tip-based
      continuous indentation process. The effects of the reverse nanoimprinting process
      and coating process on the final topography of the structures are studied. The
      experimental results show that the Raman intensity of the Au-film-coated PDMS
      substrate is influenced by the topography of the micro/nanostructures and by the
      thickness of the Au film. The Raman intensity of 1362 cm-1 R6G peak on the
      structured Au-film-coated PDMS substrate is about 8 times higher than the SERS
      tests on a commercial substrate (Q-SERS). A SERS enhancement factor ranging from
      7.5 * 105 to 6 * 106 was achieved using the structured Au-film-coated PDMS
      surface, and it was demonstrated that the method proposed in this paper is
      reliable, replicable, homogeneous and low-cost for the fabrication of SERS
      substrates.

PMID- 29181285
TI  - Molecular dynamics simulations of nanoindentation and scratch in Cu grain
      boundaries.
AB  - The dynamic nanomechanical characteristics of Cu films with different grain
      boundaries under nanoindentation and scratch conditions were studied by molecular
      dynamics (MD) simulations. The type of grain boundary is the main factor in the
      control of the substrate atoms with respect to the size of dislocations since the
      existence of the grain boundary itself restricts the movement associated with
      dislocations. In this work, we analyzed the transverse and vertical grain
      boundaries for different angles. From the simulation results, it was found that
      the sample with a transverse grain boundary angle of 20 degrees  had a higher
      barrier effect on the slip band as compared to samples with other angles.
      Moreover, the nanoindentation results (i.e., indentation on the upper area) of
      the vertical grain boundary showed that the force was translated along the grain
      boundary, thereby producing intergranular fractures.

PMID- 29181286
TI  - Photobleaching of YOYO-1 in super-resolution single DNA fluorescence imaging.
AB  - Super-resolution imaging of single DNA molecules via point accumulation for
      imaging in nanoscale topography (PAINT) has great potential to visualize fine DNA
      structures with nanometer resolution. In a typical PAINT video acquisition, dye
      molecules (YOYO-1) in solution sparsely bind to the target surfaces (DNA) whose
      locations can be mathematically determined by fitting their fluorescent point
      spread function. Many YOYO-1 molecules intercalate into DNA and remain there
      during imaging, and most of them have to be temporarily or permanently
      fluorescently bleached, often stochastically, to allow for the visualization of a
      few fluorescent events per DNA per frame of the video. Thus, controlling the
      fluorescence on-off rate is important in PAINT. In this paper, we study the
      photobleaching of YOYO-1 and its correlation with the quality of the PAINT
      images. At a low excitation laser power density, the photobleaching of YOYO-1 is
      too slow and a minimum required power density was identified, which can be
      theoretically predicted with the proposed method in this report.

PMID- 29181287
TI  - Tailoring the nanoscale morphology of HKUST-1 thin films via codeposition and
      seeded growth.
AB  - Integration of surface-anchored metal-organic frameworks (surMOFs) within
      hierarchical architectures is necessary for potential sensing, electronic,
      optical, or separation applications. It is important to understand the
      fundamentals of film formation for these surMOFs in order to develop strategies
      for their incorporation with nanoscale control over lateral and vertical
      dimensions. This research identified processing parameters to control the film
      morphology for surMOFs of HKUST-1 fabricated by codeposition and seeded
      deposition. Time and temperature were investigated to observe film formation, to
      control film thickness, and to tune morphology. Film thickness was investigated
      by ellipsometry, while film structure and film roughness were characterized by
      atomic force microscopy. Films formed via codeposition resulted in
      nanocrystallites anchored to the gold substrate. A dynamic process at the
      interface was observed with a low density of large particulates (above 100 nm)
      initially forming on the substrate; and over time these particulates were slowly
      replaced by the prevalence of smaller crystallites (ca. 10 nm) covering the
      substrate at a high density. Elevated temperature was found to expedite the
      growth process to obtain the full range of surface morphologies with reasonable
      processing times. Seed crystals formed by the codeposition method were stable and
      nucleated growth throughout a subsequent layer-by-layer deposition process. These
      seed crystals templated the final film structure and tailor the features in
      lateral and vertical directions. Using codeposition and seeded growth, different
      surface morphologies with controllable nanoscale dimensions can be designed and
      fabricated for integration of MOF systems directly into device architectures and
      sensor platforms.

PMID- 29181288
TI  - Changes of the absorption cross section of Si nanocrystals with temperature and
      distance.
AB  - The absorption cross section (ACS) of silicon nanocrystals (Si NCs) in single
      layer and multilayer structures with variable thickness of oxide barriers is
      determined via a photoluminescence (PL) modulation technique that is based on the
      analysis of excitation intensity-dependent PL kinetics under modulated pumping.
      We clearly demonstrate that roughly doubling the barrier thickness (from ca. 1 to
      2.2 nm) induces a decrease of the ACS by a factor of 1.5. An optimum separation
      barrier thickness of ca. 1.6 nm is calculated to maximize the PL intensity yield.
      This large variation of ACS values with barrier thickness is attributed to a
      modulation of either defect population states or of the efficiency of energy
      transfer between confined NC layers. An exponential decrease of the ACS with
      decreasing temperature down to 120 K can be explained by smaller occupation
      number of phonons and expansion of the band gap of Si NCs at low temperatures.
      This study clearly shows that the ACS of Si NCs cannot be considered as
      independent on experimental conditions and sample parameters.

PMID- 29181289
TI  - Numerical investigation of the tribological performance of micro-dimple textured
      surfaces under hydrodynamic lubrication.
AB  - Surface texturing is an important approach for controlling the tribological
      behavior of friction pairs used in mechanical and biological engineering. In this
      study, by utilizing the method of three-dimensional computational fluid dynamics
      (CFD) simulation, the lubrication model of a friction pair with micro-dimple
      array was established based on the Navier-Stokes equations. The typical pressure
      distribution of the lubricant film was analyzed. It was found that a positive
      hydrodynamic pressure is generated in the convergent part of the micro-dimple,
      while a negative hydrodynamic pressure is generated in the divergent part. With
      suitable parameters, the total integration of the pressure is positive, which can
      increase the load-carrying capacity of a friction pair. The effects of the micro
      dimple parameters as well as fluid properties on tribological performance were
      investigated. It was concluded that under the condition of hydrodynamic
      lubrication, the main mechanism for the improvement in the tribological
      performance is the combined effects of wedging and recirculation. Within the
      range of parameters investigated in this study, the optimum texture density is
      13%, while the optimum aspect ratio varies with the Reynolds number. For a given
      Reynolds number, there exists a combination of texture density and aspect ratio
      at which the optimum tribological performance could be obtained. Conclusions from
      this study could be helpful for the design of texture parameters in mechanical
      friction components and even in artificial joints.

PMID- 29181290
TI  - Expanding the molecular-ruler process through vapor deposition of
      hexadecanethiol.
AB  - The development of methods to produce nanoscale features with tailored chemical
      functionalities is fundamental for applications such as nanoelectronics and
      sensor fabrication. The molecular-ruler process shows great utility for this
      purpose as it combines top-down lithography for the creation of complex
      architectures over large areas in conjunction with molecular self-assembly, which
      enables precise control over the physical and chemical properties of small local
      features. The molecular-ruler process, which most commonly uses mercaptoalkanoic
      acids and metal ions to generate metal-ligated multilayers, can be employed to
      produce registered nanogaps between metal features. Expansion of this methodology
      to include molecules with other chemical functionalities could greatly expand the
      overall versatility, and thus the utility, of this process. Herein, we explore
      the use of alkanethiol molecules as the terminating layer of metal-ligated
      multilayers. During this study, it was discovered that the solution deposition of
      alkanethiol molecules resulted in low overall surface coverage with features that
      varied in height. Because features with varied heights are not conducive to the
      production of uniform nanogaps via the molecular-ruler process, the vapor-phase
      deposition of alkanethiol molecules was explored. Unlike the solution-phase
      deposition, alkanethiol islands produced by vapor-phase deposition exhibited
      markedly higher surface coverages of uniform heights. To illustrate the
      applicability of this method, metal-ligated multilayers, both with and without an
      alkanethiol capping layer, were utilized to create nanogaps between Au features
      using the molecular-ruler process.

PMID- 29181291
TI  - Surfactant-induced enhancement of droplet adhesion in superhydrophobic soybean
      (Glycine max L.) leaves.
AB  - This study performed with soybean (Glycine max L.), one of the most important
      crops for human and animal nutrition, demonstrates that changes in the leaf
      surface structure can increase the adhesion of applied droplets, even on
      superhydrophobic leaves, to reduce undesirable soil contamination by roll-off of
      agrochemical formulations from the plant surfaces. The wettability and morphology
      of soybean (Glycine max L.) leaf surfaces before and after treatment with six
      different surfactants (Agnique(r) SBO10 and five variations of nonionic
      surfactants) have been investigated. The leaf surface structures show a
      hierarchical organization, built up by convex epidermal cells (microstructure)
      and superimposed epicuticular platelet-shaped wax crystals (micro- to
      nanostructure). Chemical analysis of the epicuticular wax showed that 1
      triacontanol (C30H61OH) is the main wax component of the soybean leaf surfaces. A
      water contact angle (CA) of 162.4 degrees  (sigma = 3.6 degrees ) and tilting
      angle (TA) of 20.9 degrees  (sigma = 10.0 degrees ) were found. Adherence of pure
      water droplets on the superhydrophobic leaves is supported by the hydrophilic
      hairs on the leaves. Agnique(r) SBO10 and the nonionic surfactant XP ED 75
      increased the droplet adhesion and caused an increase of the TA from 20.9 degrees
      to 85 degrees  and 90 degrees , respectively. Scanning electron microscopy
      showed that surfactants with a hydrophilic-lipophilic balance value below 10
      caused a size reduction of the epicuticular wax structures and a change from
      Cassie-Baxter wetting to an intermediate wetting regime with an increase of
      droplet adhesion.

PMID- 29181292
TI  - Optical contrast and refractive index of natural van der Waals heterostructure
      nanosheets of franckeite.
AB  - We study mechanically exfoliated nanosheets of franckeite by quantitative optical
      microscopy. The analysis of transmission-mode and epi-illumination-mode optical
      microscopy images provides a rapid method to estimate the thickness of the
      exfoliated flakes at first glance. A quantitative analysis of the optical
      contrast spectra by means of micro-reflectance allows one to determine the
      refractive index of franckeite over a broad range of the visible spectrum through
      a fit of the acquired spectra to a model based on the Fresnel law.

PMID- 29181293
TI  - Increasing the stability of DNA nanostructure templates by atomic layer
      deposition of Al2O3 and its application in imprinting lithography.
AB  - We present a method to increase the stability of DNA nanostructure templates
      through conformal coating with a nanometer-thin protective inorganic oxide layer
      created using atomic layer deposition (ALD). DNA nanotubes and origami triangles
      were coated with ca. 2 nm to ca. 20 nm of Al2O3. Nanoscale features of the DNA
      nanostructures were preserved after the ALD coating and the patterns are
      resistive to UV/O3 oxidation. The ALD-coated DNA templates were used for a direct
      pattern transfer to poly(L-lactic acid) films.

PMID- 29181294
TI  - Electron beam induced deposition of silacyclohexane and dichlorosilacyclohexane:
      the role of dissociative ionization and dissociative electron attachment in the
      deposition process.
AB  - We present first experiments on electron beam induced deposition of
      silacyclohexane (SCH) and dichlorosilacyclohexane (DCSCH) under a focused high
      energy electron beam (FEBID). We compare the deposition dynamics observed when
      growing pillars of high aspect ratio from these compounds and we compare the
      proximity effect observed for these compounds. The two precursors show similar
      behaviour with regards to fragmentation through dissociative ionization in the
      gas phase under single-collision conditions. However, while DCSCH shows
      appreciable cross sections with regards to dissociative electron attachment, SCH
      is inert with respect to this process. We discuss our deposition experiments in
      context of the efficiency of these different electron-induced fragmentation
      processes. With regards to the deposition dynamics, we observe a substantially
      faster growth from DCSCH and a higher saturation diameter when growing pillars
      with high aspect ratio. However, both compounds show similar behaviour with
      regards to the proximity effect. With regards to the composition of the deposits,
      we observe that the C/Si ratio is similar for both compounds and in both cases
      close to the initial molecular stoichiometry. The oxygen content in the DCSCH
      deposits is about double that of the SCH deposits. Only marginal chlorine is
      observed in the deposits of from DCSCH. We discuss these observations in context
      of potential approaches for Si deposition.

PMID- 29181295
TI  - Supravaginal hysterectomy in Curacao prevalence and impact on screening for
      cervical cancer.
AB  - In Curacao, hysterectomies are frequently performed. A common reason for this
      procedure is the high incidence of leiomyomatosis. However in some cases the
      cervix is conserved. Following supravaginal hysterectomy most women discontinue
      cervical cancer screening because they think the cervix is not conserved. We
      aimed to get insight in the proportion of supravaginal hysterectomies and the
      level of awareness on the necessity to continue with cervical cancer screening in
      case of retained cervix. In 2014, data from all hysterectomies performed between
      2003 and 2013 on Curacao were collected. Information about: type of hysterectomy
      (supravaginal or not), age of the patient, reason for a hysterectomy and
      incidence of cervical cancer post-hysterectomy were obtained from the nationwide
      pathology database. In addition, 600 hysterectomised volunteers answered a
      questionnaire in which the awareness of their type of hysterectomy and
      continuation of screening for cervical cancer after surgery were investigated. In
      the at-risk population (>= 15 years old), 6.0 per1000 women (95% CI 5.9-6.2) had
      a hysterectomy between 2003 and 2013 (n = 692,304). From the performed
      hysterectomies, 2.9% were supravaginal and no cases of cervical cancer post
      hysterectomy were reported. The majority (55.3%) of women were unaware of their
      cervical status post-hysterectomy. About one-third (34.3%) of these women had
      their last Pap-smear pre-hysterectomy. Information campaigns are needed to raise
      awareness in women, to continue cervical-screening after supravaginal
      hysterectomy.

PMID- 29181296
TI  - A systematic review of physical activity interventions to improve physical
      fitness and health outcomes among Indigenous adults living in Canada.
AB  - : The Indigenous population of Canada faces an increased burden of chronic
      disease, leading to decreased life expectancy. Physical activity is an important
      health behaviour that improves chronic disease risk factors and physical fitness.
      The objective of this systematic review was to evaluate physical activity
      interventions in the Indigenous population in Canada to determine effects on
      physical activity rates, physical fitness, and health outcomes. MEDLINE,
      PsycINFO, EMBASE, and CINAHL were searched for peer-reviewed journal articles.
      Inclusion criteria were studies that examined a physical activity intervention
      delivered in Indigenous communities in Canada for adults over 18 years of age.
      Data was extracted and two authors independently rated quality of the evidence.
      Five studies were included in the narrative synthesis. Interventions were
      community-based, and three were multi-component interventions focused on
      preventing or managing type II diabetes. The interventions varied in their
      success in altering physical activity rates, with increases (n = 2), a decrease
      (n = 1), or non-significant changes reported (n = 2). No study reported any
      measure of physical fitness. BMI was reported in four studies, with only one
      reporting a significant decrease. Decreases in systolic blood pressure and total
      cholesterol were reported in two studies. There is limited evidence and a lack of
      robust interventions that examine the impacts of physical activity on health and
      fitness status in the Canadian Indigenous population. Validated, culturally
      relevant tools for measuring physical activity may aid in program evaluation and
      focused educational materials could better support population health initiatives.
      Trial registration: The review protocol was registered prospectively with
      PROSPERO (registration number: CRD42017055363).

PMID- 29181297
TI  - The ability of triggers to retrospectively predict potentially preventable
      adverse events in a sample of deceased patients.
AB  - Several trigger systems have been developed to screen medical records of
      hospitalized patients for adverse events (AEs). Because it's too labor-intensive
      to screen the records of all patients, usually a sample is screened. Our sample
      consists of patients who died during their stay because chances of finding
      preventable AEs in this subset are highest. Records were reviewed for fifteen
      triggers (n = 2182). When a trigger was present, the records were scrutinized by
      specialized medical doctors who searched for AEs. The positive predictive value
      (PPV) of the total trigger system and of the individual triggers was calculated.
      Additional analyses were performed to identify a possible optimization of the
      trigger system. In our sample, the trigger system had an overall PPV for AEs of
      47%, 17% for potentially preventable AEs. More triggers present in a record
      increased the probability of detecting an AE. Adjustments to the trigger system
      slightly increased the positive predictive value but missed about 10% of the AEs
      detected with the original system. In our sample of deceased patients the trigger
      system has a PPV comparable to other samples. However still, an enormous amount
      of time and resources are spent on cases without AEs or with non-preventable AEs.
      Possibly, the performance could be further improved by combining triggers with
      clinical scores and laboratory results. This could be promising in reducing the
      costly and labor-intensive work of screening medical records.

PMID- 29181298
TI  - Physical activity and park use of youth in Nanchang, China.
AB  - Physical inactivity is a growing issue in Chinese youth, but parks can facilitate
      traditional and non-traditional forms of physical activity for little to no cost.
      Despite this opportunity, very little is known regarding park use among Chinese
      youth. The purpose of this study was to conduct a cross-sectional observational
      study of park usage and physical activity of youth in municipal parks in
      Nanchang, China. Data were collected in June of 2014 in eight parks across
      Nanchang, Jiangxi a large city in southeast China. Physical activity was measured
      by a modified version of System for Observing Play and Recreation in Communities.
      Ordered hierarchic generalized linear models were estimated using a logit link
      function. The influence of the park was estimated using random effects, with
      fixed effects and park, environmental, and park user characteristics. Youth were
      most often seen active in the afternoon, on weekends, and during cooler times (<=
      29  degrees C). Paradoxically, more children were active when air quality was
      poorer. Older boys were more active than younger boys, but no differences were
      observed in girls. More children were seen active in unstructured play compared
      to structured activities. The results suggest parks are an important setting for
      physical activity among Chinese youth, and that unstructured activities can play
      an important role in promoting greater youth physical activity.

PMID- 29181299
TI  - Persistent bacteremia secondary to delayed identification of Lactobacillus in the
      setting of mitral valve endocarditis.
AB  - Introduction: Lactobacillus species causing infective endocarditis is rare. Most
      reported cases arise from the oral ingestion of Lactobacillus via dairy or
      nutritional supplements in patients with congenital valve disease or replacement.
      We present a case of native valve bacterial endocarditis caused by Lactobacillus
      arising from dental abscesses. Additionally, there was an error in identification
      of the Lactobacillus as Corynebacterium, which led to inadequate treatment.
      Presentation of case: A 51-year-old male presented to an outside clinic with
      several weeks of subjective fevers and malaise. The provider obtained two sets of
      blood cultures. Both grew Gram-positive bacilli identified as Corynebacterium.
      Once hospitalized he persistently had positive blood cultures despite treatment
      with vancomycin and gentamicin. The specimens were sent to a reference lab. The
      cultures were confirmed to be Lactobacillus zeae resistant to vancomycin and
      gentamicin. Once he was started on appropriate therapy his blood cultures showed
      no further growth of bacteria. The infected teeth were removed as it was felt
      they were the source of the bacteremia. Discussion: This case presents two
      interesting topics in one encounter. First, Lactobacillus is not a common culprit
      in endocarditis. Secondly, the incorrect identification of the gram-positive
      bacilli bacteria led to prolonged bacteremia in our patient. Conclusion: The
      patient was evaluated by cardiothoracic surgery at our facility and it was
      determined that he would likely need a mitral valve replacement versus repair.
      The decision was made to treat the patient with six weeks Penicillin-VK prior to
      the operation. He is currently completing his antibiotic therapy.

PMID- 29181300
TI  - Recurrence of Escherichia coli meningitis in a preterm infant and co-infection of
      echovirus 18.
AB  - Introduction: Bacterial meningitis may relapse after adequate antibiotic
      treatment. In most cases, however, the pathophysiology cannot be identified.
      Presentation of case: We describe a preterm infant with recurrent episodes of
      meningitis due to infection with an identical Escherichia coli strain both at
      birth and at 10 days after cessation of a 3 week course of appropriate antibiotic
      treatment. At the time of recurrence, the patient presented with fulminant severe
      cardiac failure due to acute myocarditis, coupled with a concurrent echovirus 18
      infection (confirmed by stool culture and serological analysis). Conclusion: Co
      infection by echovirus may underlie recurrence of Escherichia coli meningitis in
      this case.

PMID- 29181301
TI  - Glans penis necrosis following paraphimosis: A rare case with brief literature
      review.

PMID- 29181302
TI  - Pediatric urothelial carcinoma: A rare case of secondary genitorurinary
      malignancy in a Wilms Tumor patient.

PMID- 29181303
TI  - A rare case of pyonephrosis resulting from tension-free vaginal tape procedure.

PMID- 29181304
TI  - DNA vaccine expressing herpes simplex virus 1 glycoprotein C and D protects mice
      against herpes simplex keratitis.
AB  - AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1 (HSV-1)
      glycoprotein C (gC) and glycoprotein D (gD) will achieve better protective effect
      against herpes simplex keratitis (HSK) than DNA vaccine encoding gD alone.
      METHODS: DNA vaccine expressing gD or gC combined gD (gD.gC) were constructed and
      carried by chitosan nanoparticle. The expression of fusion protein gD and gC were
      detected in DNA/nanoparticle transfected 293T cells by Western-blot. For
      immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2wk
      interval, and two weeks after the final immunization, the specific immune
      responses and clinical degrees of primary HSK were evaluated. RESULTS: Fusion
      protein gD.gC could be expressed successfully in cultured 293T cells. And, pRSC
      gC.gD-IL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral
      and cellular immune response in primary HSK mice evidenced by higher levels of
      specific neutralizing antibody and sIgA production, enhanced cytotoxicities of
      splenocytes and nature killer cells (NK), when compared with those of gD alone or
      mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice
      showed least HSK disease. CONCLUSION: gC-based DNA vaccine could effectively
      prevent the progress of primary HSK, suggesting that this DNA vaccine could be a
      promising vaccine for HSK treatment in the future.

PMID- 29181305
TI  - Histopathologic findings of keratoconus corneas underwent penetrating
      keratoplasty according to topographic measurements and keratoconus severity.
AB  - AIM: To investigate the histopathologic and morphological changes of the corneas
      with keratoconus (KC) undergoing penetrating keratoplasty (PKP) according to
      topographic findings and severity of KC. METHODS: The corneal tissue of 35
      samples with KC was retrospectively evaluated with conventional light microscopy.
      Topographic and pachymetric parameters of keratoconus corneas by means of
      Pentacam such as mean keratometry (K) and central corneal thickness (CCT) were
      recorded. Severity of KC was graded according to Amsler-Krumeich classification.
      RESULTS: Epithelial thinning and breaks in Bowman's layer are the most common
      findings in keratoconus corneas (94.3% and 82.9% corneas, respectively). The
      results revealed statistically significant higher mean K value and lower CCT in
      the keratoconus corneas that were affected by epithelial thinning, breaks in the
      Bowman's layer, folds in the Descemet's membrane, epithelial scars, breaks in
      Descemet's membrane, and stromal scars than those corneas without these findings
      (P<0.05). Moreover, those corneas with epithelial thinning, breaks in the
      Bowman's layer, folds in Descemet's membrane, epithelial scars, and stromal scars
      had significantly more severe disease than those corneas without these findings
      (P<0.05). The presence of the stromal and epithelial scars were associated with
      the higher KC severity, in which, respectively, 87.5% and 80.0% of the corneas
      with stromal and epithelial scars had stage 4 of the KC severity. CONCLUSION: It
      seems that there are some specific patterns in histologic changes of the
      keratoconus corneas. The presence of pathologic findings was correlated with
      thinner and steeper corneas. Epithelial or stromal scars were associated with the
      highest disease severity. The description of histopathologic findings of KC may
      help in elucidating the pathogenesis of the disease and help pathologist in
      differentiating KC from other corneal diseases.

PMID- 29181306
TI  - Effect of itraconazole on the cornea in a murine suture model and penetrating
      keratoplasty model.
AB  - AIM: To investigate the anti-(lymph)angiogenic and/or anti-inflammatory effect of
      itraconazole in a corneal suture model and penetrating keratoplasty (PK) model.
      METHODS: Graft survival, corneal neovascularization, and corneal
      lymphangiogenesis were compared among itraconazole, amphotericin B,
      dexamethasone, phosphate buffered saline (PBS) and surgery-only groups following
      subconjunctival injection in mice that underwent PK and corneal suture.
      Immunohistochemical staining and analysis were performed in each group. Real-time
      polymerase chain reaction (RT-PCR) was performed to quantify the expression of
      inflammatory cytokines (TNF-alpha, IL-6) and vascular endothelial growth factor
      (VEGF)-A, VEGF-C, VEGFR-2, and VEGFR-3. RESULTS: In the suture model, the
      itraconazole group showed less angiogenesis, less lymphangiogenesis, and less
      inflammatory infiltration than the PBS group (all P<0.05). The itraconazole group
      showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group
      (all P<0.05). In PK model, the two-month graft survival rate was 28.57% in
      itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in
      amphotericin B group and 0 in surgery-only group. Graft survival in the
      itraconazole group was higher than that in the amphotericin, PBS and surgery-only
      group (P=0.057, 0.096, 0.012, respectively). The itraconazole group showed less
      total angiogenesis and lymphangiogenesis than PBS group (all P<0.05). CONCLUSION:
      Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in
      both a corneal suture model and PK model. Itraconazole has anti-(lymph)
      angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal
      effect and is therefore an alternative treatment option in cases where steroids
      cannot be used.

PMID- 29181307
TI  - Expression of multidrug resistance proteins in retinoblastoma.
AB  - AIM: To elucidate the mechanism of multidrug resistance in retinoblastoma, and to
      acquire more insights into in vivo drug resistance. METHODS: Three anticancer
      drug resistant Y79 human RB cells were generated against vincristine, etoposide
      or carboplatin, which are used for conventional chemotherapy in RB. Primary
      cultures from enucleated eyes after chemotherapy (PCNC) were also prepared. Their
      chemosensitivity to chemotherapeutic agents (vincristine, etoposide and
      carboplatin) were measured using MTT assay. Western blot analysis was performed
      to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins
      in retinoblastoma cells. RESULTS: Following exposure to chemotherapeutic drugs,
      PCNC showed less sensitivity to drugs. No significant changes observed in the p53
      expression, whereas Bcl-2 expression was found to be increased in the drug
      resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp)
      was observed in drug resistant Y79 cells; however there was no significant change
      in the expression of P-gp found between primary cultures of primarily enucleated
      eyes and PCNC. Multidrug resistance protein 1 (Mrp-1) expression was found to be
      elevated in the drug resistant Y79 cells as well as in PCNC. No significant
      change in the expression of lung resistance associated protein (Lrp) was observed
      in the drug resistant Y79 cells as well as in PCNC. CONCLUSION: Our results
      suggest that multidrug resistant proteins are intrinsically present in
      retinoblastoma which causes treatment failure in managing retinoblastoma with
      chemotherapy.

PMID- 29181308
TI  - Protective effect of pomegranate juice on retinal oxidative stress in
      streptozotocin-induced diabetic rats.
AB  - AIM: To investigate the effect of pomegranate juice (PJ) intake on overall
      oxidation status in retinas of diabetic rats. METHODS: Twenty-seven rats were
      divided into four groups as control (CO), diabetic (DM), control treated with PJ
      (CO-PJ), and diabetic treated with PJ (DM-PJ).The retina tissues were used to
      determine 8-hydroxy-2'-deoxyguanosine (8OHdG), malondialdehyde (MDA), reduced
      glutathione (GSH) levels, and the enzyme activities of superoxide dismutase (SOD)
      and glutathione peroxidase (GSH-Px). RESULTS: The levels of 8OHdG and MDA were
      significantly increased in the retina of DM group compared to CO group (P=0.001,
      P<0.001 respectively). Both 8OHdG and MDA levels were decreased in PJ-DM group
      compared to DM group (P=0.004, P<0.001 respectively). The activities of
      antioxidant enzymes GSH, SOD, and GDH-Px were significantly decreased in the
      retina of DM group compared to CO group (P<=0.01). GSH and GSH-Px activities were
      higher in PJ-DM group compared with DM group (P=0.010, P=0.042, respectively) but
      SOD activity was not statistically different (P=0.938). CONCLUSION: PJ intake is
      found to be effective in decreasing oxidative end products, and in increasing the
      activities of antioxidant enzymes in diabetic retinas of rats, which suggests it
      may be effective against oxidative stress in diabetic retinas.

PMID- 29181309
TI  - Effect of mistletoe combined with carboxymethyl cellulose on dry eye in
      postmenopausal women.
AB  - AIM: To investigate the protective effect of mistletoe combined with
      carboxymethyl cellulose eye drops on dry eye in postmenopausal women. METHODS:
      Sixty postmenopause female patients diagnosed of dry eye were assigned randomly
      to mistletoe combined with carboxymethyl cellulose eye drops treatment group
      (n=30) and control group treated with normal saline eye drops (n=30). The
      subjective symptoms of ocular surface, Ocular Surface Disease Index (OSDI), tear
      film function tests, tear protein and corneal morphology by confocal scanning
      microscopy were analyzed before treatment and at 1, 2, 4 and 8wk after treatment
      respectively. To ensure the safety of the trial, all patients were examined with
      systolic pressure, diastolic pressure, glutamic-pyruvic transaminase, glutamic
      oxaloacetic transaminase, urine creatinine, and blood urea nitrogen at 8wk after
      treatment. RESULTS: There were no obvious differences between two groups before
      the treatment (P>0.05). In two months after the treatment, the symptoms of ocular
      surface, OSDI, tear protein, and tear film function were only slightly changed in
      normal saline eye drops group. However, all indices were improved after the
      treatment of mistletoe combined with carboxymethyl cellulose eye drops group
      (P<0.05). In addition, the average amount of corneal epithelium basal cells and
      inflammatory cells of mistletoe treated group were 3174+/-379 and 38+/-25
      cells/mm2, significantly decreased as compared to the control group with 4309+/
      612 and 158+/- 61 cells/mm2, respectively. In the control group, although nerves
      still maintained straight under corneal epithelium, the number of nerves were
      significantly decreased, as compared with normal female. In the mistletoe treated
      group, the number of nerves was only slightly reduced, compared with normal
      female. CONCLUSION: Mistletoe combined with carboxymethyl cellulose eye drops can
      alleviate the symptoms and signs of dry eye symptoms.

PMID- 29181310
TI  - Femtosecond laser corneal refractive surgery for the correction of high myopic
      anisometropic amblyopia in juveniles.
AB  - AIM: To evaluate the effects of femtosecond laser-assisted in situ keratomileusis
      (FS-LASIK) and small-incision lenticule extraction (SMILE) to correct high myopic
      anisometropic amblyopia in juvenile patients. METHODS: From November 2013 to
      January 2015, 33 amblyopic patients with high myopic anisometropic amblyopia were
      studied. FS-LASIK (30 eyes) or SMILE (3 eyes) was performed in the amblyopic
      eyes. Visual acuity, refraction, contrast sensitivity, stereoacuity and
      complications were evaluated. Patients completed follow-up examinations at 3d,
      1mo, 3mo and the last follow-up time (mean 8.17+/-3.23mo) after surgery. RESULTS:
      The mean age at surgery was 9.04+/-3.04y (range 6-16y). The mean spherical
      equivalent in the amblyopic eyes was significantly decreased from -10.00+/-2.39 D
      preoperatively to -0.06+/-1.06 D at 1mo, -0.19+/-1.33 D at 3mo and -0.60+/-1.43 D
      at approximately 8mo postoperatively (P<0.05 for all). The mean myopic
      anisometropia was significantly decreased from -9.45+/-2.33 D preoperatively to
      +0.37+/-1.48 D at 1mo, -0.46+/-1.47 D at 3mo and -0.09+/-1.83 D at approximately
      8mo (P<0.05 for all). The logarithm of the minimum angle of resolution (logMAR)
      for uncorrected and corrected distance visual acuity (UDVA and CDVA,
      respectively) of the amblyopic eye improved from 1.74+/-0.35 and 0.98+/-0.63
      preoperatively to 0.45+/-0.31 and 0.41+/-0.33 at approximately 8mo after surgery,
      respectively. The logMAR CDVA at 3d, 1, 3 and 8mo postoperatively improved by
      means of 1.42, 2.22, 2.96, and 4.39 lines, and a gain of more than two lines
      accounted for 45%, 50%, 74% and 86% of all patients, respectively. The contrast
      sensitivity of both amblyopic eyes and dominant eyes at 0.5, 2, 8 cycles per
      degree was significantly improved postoperatively (P<0.05 for all). Of the 33
      pediatric patients, no patients had near stereopsis preoperatively and seven
      patients (21.2%) recovered near stereopsis (400" to 60") at approximately 8mo
      after surgery. No intraoperative or postoperative complications occurred in any
      patient. CONCLUSION: FS-LASIK or SMILE can be promising alternative methods to
      correct high myopic anisometropic amblyopia in juvenile patients who have failed
      with traditional approaches.

PMID- 29181311
TI  - Scanning-slit topography in patients with keratoconus.
AB  - AIM: To evaluate the anterior and posterior corneal surfaces using scanning-slit
      topography and to determine the diagnostic ability of the measured corneal
      parameters in keratoconus. METHODS: Orbscan II measurements were taken in 39
      keratoconic corneas previously diagnosed by corneal topography and in 39 healthy
      eyes. The central minimum, maximum, and astigmatic simulated keratometry (K) and
      anterior axial power values were determined. Spherical and cylindrical mean power
      diopters were obtained at the central and at the steepest point of the cornea
      both on anterior and on posterior mean power maps. Pachymetry evaluations were
      taken at the center and paracentrally in the 3 mm zone from the center at a
      location of every 45 degrees. Receiver operating characteristic (ROC) analysis
      was used to determine the best cut-off values and to evaluate the utility of the
      measured parameters in identifying patients with keratoconus. RESULTS: The
      minimum, maximum and astigmatic simulated K readings were 44.80+/-3.06 D, 47.17+/
      3.67 D and 2.42+/-1.84 D respectively in keratoconus patients and these values
      differed significantly (P<0.0001 for all comparisons) from healthy subjects. For
      all pachymetry measurements and for anterior and posterior mean power values
      significant differences were found between the two groups. Moreover, anterior
      central cylindrical power had the best discrimination ability (area under the ROC
      curve=0.948). CONCLUSION: The results suggest that scanning-slit topography and
      pachymetry are accurate methods both for keratoconus screening and for
      confirmation of the diagnosis.

PMID- 29181312
TI  - Phacoemulsification combined with transpupillary removal of silicone oil and
      intracapsular intraocular lens implantation.
AB  - AIM: To estimate the effectiveness of phacoemulsification and foldable
      intraocular lens (IOL) implantation combined with transpupillary silicone oil
      removal. METHODS: There were 168 eyes of 168 candidate patients with cataract and
      silicone oil-filled eyes recruited in our study. All of the patients received the
      intraocular silicone oil removal surgery by transpupillary drainage and cataract
      extraction by phacoemulsification. Then the IOL implantation were also performed
      through corneal incision. RESULTS: The surgery was successfully completed in all
      eyes. Best corrected visual acuity (BCVA) and postoperative complications were
      recorded in three months after surgery. There were 143 eyes with BCVA improved,
      otherwise 25 eyes remained stable at the last follow-up visit. The mean BCVA
      statistically improved from 20/400+/-0.02 to 20/100+/-0.15 (P<0.001) and mean
      postoperative IOP was 13.85+/-2.18 mm Hg (P=0.415). No intra-operative
      complications were reported. CONCLUSION: Phacoemulsification combined with
      transpupillary removal of silicone oil is a safe and simple effective method. In
      general, it enables quick recovery of visual acuity with less complication rate.

PMID- 29181313
TI  - Prospective study of Centurion(r) versus Infiniti(r) phacoemulsification systems:
      surgical and visual outcomes.
AB  - AIM: To evaluate surgical outcomes (SOs) and visual outcomes (VOs) in cataract
      surgery comparing the Centurion(r) phacoemulsification system (CPS) with the
      Infiniti(r) phacoemulsification system (IPS). METHODS: Prospective, consecutive
      study in a single-site private practice. Totally 412 patients undergoing cataract
      surgery with either the CPS using the 30-degree balanced(r) tip (n=207) or the
      IPS using the 30-degree Kelman(r) tip (n=205). Intraoperative and postoperative
      outcomes were documented prospectively up to one month follow-up. Nuclear
      sclerosis (NS) grade, cumulated dissipated energy (CDE), preoperative corrected
      distance visual acuity (CDVA), and CDVA at one month were recorded. RESULTS: CDE
      was 13.50% less in the whole CPS compared with the whole IPS subcohort. In eyes
      with NS grade III or greater, CDE was 28.87% less with CPS (n=70) compared with
      IPS (n=44) (P=0.010). Surgical complications were not statistically different
      between the two subcohorts (P=0.083), but in the one case of vitreous loss using
      the CPS, CDVA of 6/4 was achieved at one month. The mean CDVAs (VOs) at one month
      for NS grade III and above cataracts were -0.17 logMAR (6/4.5) in the CPS and 
      0.15 logMAR (6/4.5) in the IPS subcohort respectively (P=0.033). CONCLUSION: CDE
      is 28.87% less, and VOs are significantly improved, in denser cataracts in the
      CPS compared with the IPS. The authors recommend the CPS for cases with denser
      nuclei.

PMID- 29181314
TI  - Repeatability of Ophtha Top topography and comparison with IOL-Master and
      LenstarLS900 in cataract patients.
AB  - AIM: To determine the repeatability of Ophtha Top topography and assess the
      consistency with intraocular lens (IOL)-Master and LenstarLS900 (Lenstar) in
      measuring corneal parameters among cataract patients. METHODS: Totally 125 eyes
      were enrolled. Corneas were successively measured with Ophtha Top, IOL-Master and
      Lenstar at least three times. The flattest meridian power (Kf), the steepest
      meridian power (Ks), mean power (Km), J0 and J45 were recorded. Intra-class
      correlation coefficients (ICCs), the coefficient of variance (COV), within
      subject standard deviation (Sw), and test-retest repeatability (2.77Sw) were
      adopted to determine the repeatability. The 95% limit of agreement (95%LOA) and
      Bland-Altman plots were used to assess comparability. RESULTS: Repeatability of
      Ophtha Top topography for measuring corneal parameters showed the ICCs were all
      above 0.93, 2.77Sw was lower than 0.31, and the COV of the Kf and Ks was lower
      than 0.25. The keratometric readings with Ophtha Top topography were flatter than
      with the IOL-Master and Lenstar devices, while the Pearson correlation
      coefficients were over 0.97. The J0 and J45 with Ophtha Top topography were
      smaller compared with Lenstar and IOL-Master, while was comparable between
      Lenstar and IOL-Master. CONCLUSION: Ophtha Top topography shows excellent
      repeatability for measuring corneal parameters. However, differences between the
      Ophtha TOP topography and Lenstar, IOL-Master both in cornea curvature and the
      astigmatism should be noted clinically.

PMID- 29181315
TI  - Bimanual microincision cataract surgery with implantation of the new Incise(r)
      MJ14 intraocular lens through a 1.4 mm incision.
AB  - AIM: To analyze the visual outcomes and the posterior capsule opacification (PCO)
      with the new Incise(r) MJ14 intraocular lens (IOL) implanted through a 1.4 mm
      clear corneal incision (CCI) in patients who underwent bimanual microincision
      cataract surgery (B-MICS). METHODS: Eighty eyes which underwent cataract surgery
      using B-MICS technique performed by the same experienced surgeon were included in
      the study: 40 eyes were implanted with an Incise(r) MJ14 IOL through a 1.4 mm CCI
      (group A) without enlargement of the main CCI, while 40 eyes were implanted with
      an Akreos(r) MI60 IOL with enlargement of the main CCI to 1.8 mm (group B). Best
      corrected visual acuity (BCVA), astigmatism and endothelial cell loss were
      evaluated before and after surgery at 7, 30d and 6mo. Anterior segment-optical
      coherence tomography (AS-OCT) of CCI was performed at 1, 3, 7, 30d, 6 and 18mo.
      PCO incidence was evaluated at 18mo using EPCO 2000 Software. RESULTS: Mean BCVA
      improvement and endothelial cell loss were statistically significant at 18mo in
      both groups with no difference between the two groups; no statistically
      significant difference in surgically induced astigmatism (SIA) was noticed in the
      two groups. At AS-OCT the only significant alterations in the CCI were
      endothelial gaping and local detachment of Descemet's membrane at 1 and 7d after
      surgery; no statistically significant alterations were found at 1, 6 and 18mo.
      PCO score at 18mo was 0.03+/-0.07 for group A and 0.08+/-0.18 for group B
      (P=0.11) with no sign of central optic plate invasion in both groups. CONCLUSION:
      The implant of the new Incise(r) MJ14 IOL through a 1.4 mm CCI and B-MICS
      technique appeared to be a safe and effective procedure with rapid visual
      recovery. PCO rate resulted very low and the CCI presented few morphological
      alterations which were only detectable in the first days postoperatively and
      achieved fast corneal healing during the long-term follow-up.

PMID- 29181316
TI  - The prognostic value of lymphocyte-to-monocyte ratio in retinopathy of
      prematurity.
AB  - AIM: To evaluate the associations between development of retinopathy of
      prematurity (ROP) and serum lymphocyte-to-monocyte ratio (LMR), neutrophil-to
      lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). METHODS: A
      retrospective cohort study was performed, involving infants who were screened for
      ROP from January 2015 to December 2015. Preterm newborns of <=32 gestational
      weeks with ROP were enrolled as the observation group, and non-ROP infants were
      enrolled as the control group, whose complete blood cell were measured within the
      first 24h of life. The levels of NLR, LMR and PLR were determined in all groups.
      The data obtained were analyzed using univariate and multivariate logistic
      regression analysis. RESULTS: In this study, 40 cases of ROP were enrolled and 40
      cases of non-ROP as controls. The LMR levels were significantly higher (P<0.001)
      in ROP group (3.96+/-1.16) compared to non-ROP group (2.85+/-0.79). The NLR
      levels were significantly lower (P=0.035) in ROP group {median [interquartile
      range (IQR)], 0.88 (0.67-1.46)} compared to non-ROP group [median (IQR), 1.20
      (0.85-1.89)]. The median PLR values were 61.99 (IQR, 50.23-75.98) in ROP group
      and 69.24 (IQR, 55.52-88.12) in non-ROP group (P=0.104). Logistic regression
      analysis suggested that LMR was an independent risk factor for ROP (OR: 0.275;
      95% CI: 0.134-0.564; P=0.001). CONCLUSION: The findings demonstrate that higher
      LMR is independently and significantly associated with the development of ROP,
      and the LMR may be invoked as a predictive tool for identifying risk for ROP.

PMID- 29181317
TI  - A predictive score for retinopathy of prematurity by using clinical risk factors
      and serum insulin-like growth factor-1 levels.
AB  - AIM: To detect the impact of insulin-like growth factor-1 (IGF-1) and other risk
      factors for the early prediction of retinopathy of prematurity (ROP) and to
      establish a scoring system for ROP prediction by using clinical criteria and
      serum IGF-1 levels. METHODS: The study was conducted with 127 preterm infants.
      IGF-1 levels in the 1st day of life, 1st, 2nd, 3rd and 4th week of life was
      analyzed. The score was established after logistic regression analysis,
      considering the impact of each variable on the occurrences of any stage ROP. A
      validation cohort containing 107 preterm infants was included in the study and
      the predictive ability of ROP score was calculated. RESULTS: Birth weights (BW),
      gestational weeks (GW) and the prevalence of breast milk consumption were lower,
      respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and
      necrotizing enterocolitis (NEC) were more frequent, the duration of mechanical
      ventilation and oxygen supplementation was longer in patients with ROP (P<0.05).
      Initial serum IGF-1 levels tended to be lower in newborns who developed ROP.
      Logistic regression analysis revealed that low BW (<1250 g), presence of
      intraventricular hemorrhage (IVH) and formula feeding increased the risk of ROP.
      Afterwards, the scoring system was validated on 107 infants. The negative
      predictive values of a score less than 4 were 84.3%, 74.7% and 79.8% while
      positive predictive values were 76.3%, 65.5% and 71.6% respectively. CONCLUSION:
      In addition to BW <1250 g and IVH, formula consumption was detected as a risk
      factor for the development of ROP. Breastfeeding is important for prevention of
      ROP in preterm infants.

PMID- 29181318
TI  - Validity of automated refraction after segmented refractive multifocal
      intraocular lens implantation.
AB  - AIM: To evaluate the clinical utility of automated refraction (AR) and
      keratometry (KR) compared with subjective or manifest refraction (MR) after
      cataract or refractive lens exchange surgery with implantation of Lentis Mplus X
      (Oculentis GmbH) refractive multifocal intraocular lens (IOL). METHODS: Eighty
      six eyes implanted with the Lentis Mplus X multifocal IOL were included. MR was
      performed in all patients followed by three consecutive AR measurements using the
      Topcon KR-8000 autorefractor. Assessment of repeatability of consecutive AR
      before and after dilation with phenylephrine 10%, and comparison of the AR and KR
      with MR using vector analysis were performed at 3mo follow-up. RESULTS: Analysis
      showed excellent repeatability of the AR measurements. Linear regression of AR
      versus MR showed good correlation for sphere and spherical equivalent, whereas
      the correlation for astigmatism was low. The mean difference AR-MR was -1.28+/
      0.29 diopters (D) for sphere. Astigmatism showed better correlation between KR
      and MR. CONCLUSION: We suggest AR sphere plus 1.25 D and the KR cylinder as the
      starting point for MR in eyes with a Lentis Mplus X multifocal IOL. If AR
      measurements are equal to MR, decentration of the IOL should be suspected.

PMID- 29181319
TI  - The effect of cataract surgery on sleep quality: a systematic review and Meta
      analysis.
AB  - AIM: To evaluate the effect of cataract surgery on sleep quality and to compare
      the difference between ultraviolet-blocking clear intraocular lens (UVB-IOL) and
      blue-filtering intraocular lens (BF-IOL) implantation. METHODS: Electronic search
      was performed of PubMed, MEDLINE, Embase and the Cochrane Library up to January
      2016. Studies were eligible when they evaluated the sleep quality before and
      after cataract surgery by Pittsburgh sleep quality index (PSQI). A random/fixed
      effects Meta-analysis was used for the pooled estimate. Heterogeneity was
      assessed with the I2 test. RESULTS: Six studies were selected from 5623
      references. Cataract surgery significantly reduced the PSQI scores at
      postoperative 0-3mo [mean difference (MD) =-0.62, 95%CI: -1.14 to -0.11, P=0.02,
      I2=66%] and 3-12mo (MD=-0.32, 95%CI: -0.62 to -0.02, P=0.04, I2=0), respectively.
      Considering different intraocular lens (IOL) implantations, relative post
      operative PSQI reduction was found for both UVB-IOL and BF-IOL, but a significant
      reduction was detected only for UVB-IOL. No significant difference was found with
      the effect of BF-IOL vs UVB-IOL on sleep quality. CONCLUSION: This study found
      that cataract surgery significantly improved the PSQI score-derived subjective
      sleep quality irrespective of the IOL type implanted. These findings highlight a
      substantial benefit of cataract surgery on systemic health with photoreceptive
      restoration in addition to visual acuity improvements.

PMID- 29181320
TI  - Predictive factors of visual function recovery after pituitary adenoma resection:
      a literature review and Meta-analysis.
AB  - AIM: To determine the dominant predictive factors of postoperative visual
      recovery for patients with pituitary adenoma. METHODS: PubMed, Google Scholar,
      Web of Science and Cochrane Library were searched for relevant human studies,
      which investigated the prediction of the postoperative visual recovery of
      patients with pituitary adenoma, from January 2000 to May 2017. Meta-analyses
      were performed on the primary outcomes. After the related data were extracted by
      two independent investigators, pooled weighted mean difference (WMD) and odds
      ratio (OR) with 95% confidence interval (CI) were estimated using a random
      effects or a fixed-effects model. RESULTS: Nineteen studies were included in the
      literature review, and nine trials were included in the Meta-analysis, which
      comprised 530 patients (975 eyes) with pituitary adenoma. For the primary
      outcomes, there was a significant difference between preoperative and
      postoperative mean deviation (MD) values of the visual field (WMD -5.85; 95%CI: 
      8.19 to -3.51; P<0.00001). Predictive characteristics of four factors were
      revealed in this Meta-analysis by assigning the patients to sufficient and
      insufficient groups according to postoperative visual field improvements,
      including preoperative visual field defect (WMD 10.09; 95%CI: 6.17 to 14.02;
      P<0.00001), patient age (WMD -12.32; 95%CI: -18.42 to -6.22; P<0.0001), symptom
      duration (WMD -5.04; 95%CI: -9.71 to -0.37; P=0.03), and preoperative
      peripapillary retinal nerve fiber layer (pRNFL) thickness (OR 0.1; 95% CI: 0.04
      to 0.23; P<0.00001). CONCLUSION: Preoperative visual field defect, symptom
      duration, patient age, and preoperative pRNFL thickness are the dominant
      predictive factors of the postoperative recovery of the visual field for patients
      with pituitary adenoma.

PMID- 29181323
TI  - A new interpretation and quantitative method for diplopia test: 304 cases of
      ocular motor nerve palsy for clinical test and verify.
AB  - We introduce a new interpretation and quantitative method for computerized
      diplopia test. By comparing this new method to the Hess screen test, we validate
      its applicability among 304 patients with ocular motor nerve palsy. This new
      method shows great assistant value as the Hess screen test in making accurate
      diagnosis and quantitative evaluation the severity of diplopia. Furthermore, it
      is more convenient and suitable for daily clinical use.

PMID- 29181322
TI  - Potential role of Muller cells in the pathogenesis of macropsia associated with
      epiretinal membrane: a hypothesis revisited.
AB  - Pathophysiological explanations for metamorphopsia associated with retinal
      pathologies generally focus on photoreceptor organization disruption. However,
      the retinal microarchitecture is complicated, and we hypothesize that other
      retinal cells may also be involved. Metamorphopsia has been widely studied in
      eyes with epiretinal membranes and we revisit the idea that Muller cell
      displacement causes retinal macropsia. A PubMed query and related article search
      for the macula ultrastructure under normal and pathological conditions revealed
      an enormous amount of information, particularly ultrahigh definition optical
      coherence tomography and other retinal imaging modality studies. Findings of
      these imaging studies support our hypothesis that Muller cells, and not cone
      photoreceptors, are primarily responsible for macropsia in eyes with epiretinal
      membranes. More specifically, we conclude that displacement of Muller cell
      endfeet, and not photoreceptor cones, is a more likely the explanation for
      retinal macropsia associated with epiretinal membranes.

PMID- 29181324
TI  - The prevalence of uncorrected refractive error in urban, suburban, exurban and
      rural primary school children in Indonesian population.
AB  - Uncorrected refractive error (URE) is a major health problem among school
      children. This study was aimed to determine the frequency and patterns of URE
      across 4 gradients of residential densities (urban, exurban, suburban and rural).
      This was a cross-sectional study of school children from 3 districts in
      Yogyakarta and 1 district near Yogyakarta, Indonesia. The information regarding
      age, sex, school and school grader were recorded. The Snellen's chart was used to
      measure the visual acuity and to perform the subjective refraction. The district
      was then divided into urban, suburban, exurban and rural area based on their
      location and population. In total, 410 school children were included in the
      analyses (urban=79, exurban=73, suburban=160 and rural=98 school children). Urban
      school children revealed the worst visual acuity (P<0.001) and it was significant
      when compared with exurban and rural. The proportion of URE among urban,
      suburban, exurban and rural area were 10.1%, 12.3%, 3.8%, and 1%, respectively,
      and it was significant when compared to the proportion of ametropia and corrected
      refractive error across residential densities (P=0.003). The risk of URE
      development in urban, suburban, exurban, and rural were 2.218 (95%CI: 0.914
      5.385), 3.019 (95%CI: 1.266-7.197), 0.502 (95%CI: 0.195-1.293), and 0.130
      (95%CI:0.017-0.972), respectively. Urban school children showed the worst visual
      acuity. The school children in urban and suburban residential area had 2 and 3
      times higher risk of developing the URE.

PMID- 29181321
TI  - Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and
      update.
AB  - Adaptive optics scanning laser ophthalmoscopy (AO-SLO) has been a promising
      technique in funds imaging with growing popularity. This review firstly gives a
      brief history of adaptive optics (AO) and AO-SLO. Then it compares AO-SLO with
      conventional imaging methods (fundus fluorescein angiography, fundus
      autofluorescence, indocyanine green angiography and optical coherence tomography)
      and other AO techniques (adaptive optics flood-illumination ophthalmoscopy and
      adaptive optics optical coherence tomography). Furthermore, an update of current
      research situation in AO-SLO is made based on different fundus structures as
      photoreceptors (cones and rods), fundus vessels, retinal pigment epithelium
      layer, retinal nerve fiber layer, ganglion cell layer and lamina cribrosa.
      Finally, this review indicates possible research directions of AO-SLO in future.

PMID- 29181325
TI  - The use of choline in association with the Bangerter filters for the treatment of
      amblyopia.
AB  - The study investigated the effects of choline combined with Bangerter filter in
      the treatment of amblyopia. All amblyopic subjects used a Bangerter filter on the
      corrective spectacle lens (1d over the left eye, 1d over the right eye). Choline
      was then administered orally to 39 patients once daily, five days per week for
      the entire study period. Subjects treated with the Bangerter filter showed a mean
      visual acuity of 0.27 logMAR; at 12mo of treatment, the mean visual acuity
      reached 0.09 logMAR. Patients treated with the Bangerter filter and citicoline
      showed a mean visual acuity of 0.35 logMAR; at 12mo of treatment, the mean visual
      acuity reached 0.01 logMAR. No significant changes in the angle of deviation were
      observed in both groups. Subjects in both forms of amblyopia therapies
      demonstrated an increase in visual acuity. However, these effects were markedly
      enhanced when coupled with the administration of choline. Findings suggest that
      the effects are particularly relevant in the more severe amblyopic cases.

PMID- 29181326
TI  - Optical coherence tomography changes following vitrectomy for long standing
      premacular hemorrhage in Valsalva retinopathy.

PMID- 29181327
TI  - Acquired ptosis associated with oculomotor and contralateral facial nerve
      synkinesis: the first reported case.

PMID- 29181328
TI  - Combined penetrating keratoplasty, pars plana vitrectomy and Ahmed glaucoma valve
      implant after open globe injury: a challenging approach.

PMID- 29181329
TI  - Comment on "The diurnal variation pattern of choroidal thickness in macular
      region of young healthy female individuals using spectral domain optical
      coherence tomography".

PMID- 29181330
TI  - Evaluation of Admission Indications, Clinical Characteristics and Outcomes of
      Obstetric Patients Admitted to the Intensive Care Unit of a Teaching Hospital
      Center: A Five-Year Retrospective Review.
AB  - Background: Care of obstetric patients has always been a challenge for critical
      care physicians, because in addition to their complex pregnancy-related disease,
      fetal viability is considered. Objectives: The aim of this study was to review
      the admission indications, clinical characteristics and outcomes of obstetric
      patients, admitted to the intensive care unit of Alzzahra teaching hospital
      affiliated to Guilan University of Medical Sciences, Rasht, Iran. Methods: This
      retrospective cohort study was conducted on pregnant /post-partum (up to 6 weeks)
      patients admitted to the ICU over a 5-year period from April 2009 to April, 2014.
      Results: Data from 1019 subjects were analyzed. Overall, 90.1% of the patients
      were admitted in the postpartum period. The most common indications for admission
      were pregnancy related hypertensive disorders (27.5%) and obstetric hemorrhage
      (13.5%). Epilepsy (5.4%) and cardiac disease (5.2%) were the most common non
      obstetric indications. Conclusions: Pregnancy-related hypertensive disorders and
      obstetric hemorrhage were the main reasons for admission, and epilepsy and
      cardiac disease were the most common non-obstetric indications. Efforts must be
      concentrated on increasing antenatal care.

PMID- 29181331
TI  - Effect of Intravenous Acetaminophen on Postoperative Pain in Vitrectomy: A
      Randomized, Double-Blind, Clinical Trial.
AB  - Background: Nowadays, pain, nausea, and vomiting are regarded as important
      complications of anesthesia and surgery. The current study aimed at assessing the
      effect of preemptive intravenous acetaminophen on control of pain, nausea,
      vomiting, shivering, and drowsiness following the general anesthesia for retina
      and/or vitrectomy surgeries. Methods: In a randomized, double-blind, clinical
      trial, 83 candidates for retina or vitrectomy eye surgery under general
      anesthesia were distributed into 3 groups: A) 41 patients in the control group
      who received 100 mL of normal saline just before the surgery and 100 mL of normal
      saline 20 minutes before the end of surgery; B) 21 patients in the preemptive
      group who received acetaminophen 15 mg/kg in 100 mL normal saline just before the
      surgery and 100 mL normal saline 20 minutes before the end of surgery; C) 21
      patients in the preventive group who received 100 mL normal saline just before
      the surgery and acetaminophen 15 mg/kg in 100 mL normal saline 20 minutes before
      the end of surgery. Pain, nausea, vomiting, and shivering were assessed at the
      recovery and 2, 4, and 24 hours after the operation. Anesthesia emergence
      situation was assessed after arrival in the recovery room by the Richmond
      agitation-sedation scale (RASS) questionnaire. Blood pressure and heart rate were
      recorded before anesthesia induction, just after intubation, before extubation,
      and on discharge from the recovery room. Results: Total intraoperative fentanyl,
      duration of operation, and duration of anesthesia were not different among the
      studied groups. Vital signs were not statistically different among the groups at
      before anesthesia induction, just after intubation, before extubation, and on
      discharge from the recovery room. Thirty-three patients in the control group
      (87.8%), 11 in preemptive (52.4%), and 14 in preventive groups (66.7%) needed
      acetaminophen in the first 24 hours after the surgery (P value = 0.008). Pain
      scores measured by visual rating scale (VRS) was lower in the preemptive and
      preventive groups, compared with those of the control group, in the recovery (P
      value = 0.006), 2 hours after the surgery (P value = 0.008), and 4 hours after
      the surgery (P value = 0.012), but not in 24 hours after the operation (P value =
      0.1). Conclusions: Intravenous acetaminophen administered as preemptive or
      preventive medication was effective and safe to control acute postoperative pain
      and analgesic request after the vitrectomy eye surgery.

PMID- 29181332
TI  - Intravenous Midazolam as More Effective Than Propofol for Preventing Pruritus
      After Intrathecal Sufentanil in Surgical Patients: A Randomized Blinded Trial.
AB  - Background: Pruritus is a troublesome side effect of intrathecal opioids.
      Midazolam can reinforce GABA-mediated inhibition of the medullary dorsal horn
      neurons, and thus theoretically has potential to suppress opioid-induced
      pruritus. Objectives: This prospective double-blinded randomized trial aimed at
      comparing the effects of propofol, midazolam, and a combination of the two on the
      prevention of pruritus induced by intrathecal sufentanil. Methods: Eighty-four
      patients undergoing spinal anesthesia with 3 mL hyperbaric bupivacaine 0.5% and 5
      MUg sufentanil (1 mL) were randomly allocated to one of the three study groups:
      Group 1, who were administered 20 mg intravenous (IV) propofol bolus, then 50
      MUg/kg/min IV infusion; Group 2, who were administered 0.03 mg/kg IV midazolam
      bolus, then 0.02 mg/kg/h IV infusion; and Group 3, who were administered 10 mg IV
      propofol and 0.015 mg/kg IV midazolam bolus, then 25 MUg/kg/min propofol and 0.01
      mg/kg/h midazolam IV infusion. The incidence rates and severity of pruritus were
      assessed intraoperatively and postoperatively for 24 hours. Results: The Ramsay
      Sedation Score was highest for the propofol group throughout the duration of the
      anesthetic process. Overall, 17 patients in the propofol group (60.7%), eight
      patients in the midazolam group (28.6%), and nine patients in the propofol
      midazolam group (32.1%) developed pruritus (P = 0.027). Intraoperative pruritus
      was observed in seven patients in the propofol group (25%), two patients in the
      midazolam group (7.1%), and five patients in the midazolam-propofol group (17.9%)
      (P = 0.196). Postoperative pruritus developed in 12 patients in the propofol
      group (42.9%), six patients in the midazolam group (21.4%), and four patients in
      the midazolam-propofol group (14.3%) (P = 0.041). There was no significant
      difference between the groups with respect to the severity of pruritus (P >
      0.05). Conclusions: This study showed that in comparison with propofol, the
      administration of 0.03 mg/kg IV midazolam bolus followed by 0.02 mg/kg/h could be
      more effective in the prevention of intrathecal sufentanil-induced pruritus
      without increasing sedation and other side effects.

PMID- 29181333
TI  - Developing Cervical Hematoma Following Jaw Thrust Maneuver Triggered Diagnosis of
      Neurofibromatosis: A Case Report and Brief Literature Review.
AB  - A 25-year-old man underwent an excision of a thigh mass under general anesthesia
      without any complication. After the operation, he developed oxygen desaturation
      requiring a jaw thrust maneuver. A rapidly expanding hematoma on the right side
      of the neck was formed shortly after the application of the maneuver. The patient
      was returned to the operation room for a neck exploration. Damage to the facial
      artery and vein was noted. Further evaluations confirmed the diagnosis of
      Neurofibromatosis type 1 (NF-1). It is recommended that considering the probable
      risk of arising hematoma in NF-1 patients, application of jaw thrust maneuver
      should be performed meticulously.

PMID- 29181336
TI  - Editorial: Oncolytic Viruses-Genetically Engineering the Future of Cancer
      Therapy.

PMID- 29181335
TI  - Perceived Workplace Stress Is Associated with an Increased Risk of Prostate
      Cancer before Age 65.
AB  - Background: Evidence is lacking regarding the potential role of chronic
      psychological stress on cancer incidence. The workplace is reported to be the
      main source of stress among Canadian men. We examined the association between
      perceived lifetime workplace stress and prostate cancer (PCa) risk in a large
      case-control study. Methods: Cases were 1,933 men, aged <= 75 years, newly
      diagnosed with PCa in 2005-2009 across hospitals in Montreal, Canada.
      Concurrently, 1994 population controls frequency-matched on age were randomly
      selected from the electoral list based on cases' residential districts. Detailed
      lifestyle and work histories (including perceived stress, from any type of work
      stressor, for each job held) were collected during in-person interviews. Logistic
      regression was used to estimate odds ratios (OR) and 95% confidence intervals
      (CI) for the association between work-related stress and PCa risk in multivariate
      analyses. Results: Over the lifetime, 58% of subjects reported at least one job
      as stressful. Occupations described as stressful were most often among white
      collar workers. Perceived workplace stress duration was associated with a higher
      risk of PCa (OR = 1.12, 95% CI:1.04-1.20 per 10-year increase) among men younger
      than 65 years, but not among older men. Associations were similar irrespective of
      PCa aggressiveness. Frequent or recent screening for PCa, age at first exposure
      and time since exposure to work-related stress, and socioeconomic and lifestyle
      factors, had little influence on risk estimates. Conclusion: Findings are in line
      with an association between reporting prolonged workplace stress and an increase
      in risk of PCa before age 65.

PMID- 29181334
TI  - Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.
AB  - Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that
      usually exist in a quiescent state, only entering the cell cycle to replenish the
      blood compartment, thereby limiting the potential for errors in replication.
      Inflammatory signals that are released in response to environmental stressors,
      such as infection, trigger active cycling of HSCs. These inflammatory signals can
      also directly induce HSCs to release cytokines into the bone marrow environment,
      promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs
      require intracellular signaling programs to deactivate this response and return
      to steady state. Prolonged or excessive exposure to inflammatory cytokines, such
      as in prolonged infection or in chronic rheumatologic conditions, can lead to
      continued HSC cycling and eventual HSC loss. This promotes bone marrow failure,
      and can precipitate preleukemic states or leukemia through the acquisition of
      genetic and epigenetic changes in HSCs. This can occur through the initiation of
      clonal hematopoiesis, followed by the emergence preleukemic stem cells (pre
      LSCs). In this review, we describe the roles of multiple inflammatory signaling
      pathways in the generation of pre-LSCs and in progression to myelodysplastic
      syndrome (MDS), myeloproliferative neoplasms, and acute myeloid leukemia (AML).
      In AML, activation of some inflammatory signaling pathways can promote the
      cycling and differentiation of LSCs, and this can be exploited therapeutically.
      We also discuss the therapeutic potential of modulating inflammatory signaling
      for the treatment of myeloid malignancies.

PMID- 29181337
TI  - The Many-Faced Program of Epithelial-Mesenchymal Transition: A System Biology
      Based View.
AB  - System biology uses a range of experimental and statistical methods to dissect
      complex processes that results from alterations in biological models. Given the
      complexity of the epithelial-mesenchymal transition (EMT) program, system biology
      represents a promising approach to understanding its fine molecular regulation by
      the interpretation of high-throughput datasets. Herein, we review recent
      contributions of system biology applied to the field of EMT physiology and
      illustrate the importance of these approaches to model biological networks that
      are perturbed during the transition. Together, these results allowed the
      definition of an EMT signature across different tumor types, the identification
      of dysregulated processes and new modules of regulation, making possible to
      reveal the EMT molecular visage underneath.

PMID- 29181338
TI  - Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus
      Infection.
AB  - The mechanisms of hepatitis B virus (HBV) persistent infection are not completely
      understood. Interleukin (IL)-35, which is a newly identified cytokine belongs to
      IL-12 family, has been demonstrated to induce immunotolerance. Thus, the aim of
      current study was to investigate the role of IL-35 during chronic HBV infection.
      A total of 61 patients with chronic HBV infection [37 chronic hepatitis B (CHB)
      and 24 asymptomatic HBV carriers (ASC)] and 20 healthy individuals were enrolled.
      IL-35 concentration as well as the modulatory function of IL-35 on
      CD4+CD25+CD127dim/- regulatory T cells (Tregs) and on HBV antigen-specific CD8+ T
      cells was investigated. IL-35 expression was significantly increased in both CHB
      and ASC, and was positively correlated with the levels of HBV DNA. Inhibition of
      viral replication induced the reduction in serum levels of IL-35. IL-35
      stimulation led to inhibition of proinflammatory cytokine productions and
      elevation of apoptosis in peripheral blood mononuclear cells (PBMCs), but not in
      HepG2.2.15 cells. Moreover, IL-35 stimulation not only robustly inhibited
      cellular proliferation, but also up-regulated the production of IL-10 and IL-35
      in a HBV antigen-specific and non-specific manner in Tregs/CD4+CD25- T cells
      coculture system, which indicated enhancement of suppressive function of Tregs.
      Furthermore, IL-35 also reduced both cytolytic activity (direct lysis of
      HepG2.2.15 cells) and noncytolytic function (IFN-gamma and TNF-alpha production)
      of HBV antigen-specific CD8+ T cells. The current data suggested that IL-35
      contributed to maintain viral persistence by suppressing antiviral immune
      responses and reducing inflammatory responses in chronic HBV infection.

PMID- 29181339
TI  - Retraction: Synergistic combination of violacein and azoles that leads to
      enhanced killing of major human pathogenic dermatophytic fungi Trichophyton
      rubrum.
AB  - [This retracts the article on p. 57 in vol. 5, PMID: 26322275.].

PMID- 29181340
TI  - Smearing of Open Access by Predatory Journals: Difficulty of being Good.

PMID- 29181341
TI  - Odontoideum Bone Revealed by c1-c2 Dislocation of the Cervical Spine during a
      Diving Accident.
AB  - Introduction: Odontoideum bone or the mobile odontoid process is one of the
      rarest malformations of the cervico-occipital hinge. It exposes to the atlo-axial
      instability and to the risk of bulbo-medullary compression threatening then the
      vital and functional prognosis. We report the case of a 16-year-old patient who
      was the victim of a raod accident resulting in acervical spine injury.
      Radiological investigation found an odontoideum bone malformation associated with
      C1C2 dislocation. Case Report: A 16-year-old patient with no medical history had
      a road accident. Clinical evaluation found an incomplete tetraplegia.The imaging
      has revealed an atlo-axoidal dislocation with aspinal cord compression.
      Furthermore, radiological exams relvealed an odentoideum bone. A transcranial
      traction by a Gardner stirrup was set for 15 days to obtain a progressive
      reduction of the displacement. A full neurological recovery (FB-FD) was
      obtained.The patient was then operated to stabilize the reduction. A C1-C2
      posterior zygapophyseal arthrodesis was performed. An autograft harvested from
      the iliac crest was used. Complementary open reduction and fixation of the
      cervico-occipital hinge was made using lamellar hooks and compression rods. At
      the 18-month follow-up, the clinical examination found no neurological deficiency
      and the plain radiography showed a complete fusion of the arthrodesis.
      Conclusion: Odontoideum bone is a rare and potentially life-threatening
      malformation. It is most often asymptomatic but symptoms could occur any time
      after a benign trauma. The prognosis mainly depends on the precocity of the
      management. Preventive surgery is recommended byseveral authorsin case
      ofinstability.

PMID- 29181342
TI  - Early Loosening of Spinal Rod in a Case of Degenerative Grade 1 Spondylolisthesis
      treated with Unilateral Pedicle Screw Fixation and Transforaminal Cage for
      Interbody Fusion.
AB  - Introduction: Unilateral pedicle screw fixation and transforaminal cage for
      interbody fusion are well-established form of treatment for lumbar
      spondylolisthesis. It is cost effective and has shown to have a comparable
      outcome to bilateral pedicle screw fixation. We present a case of unilateral
      pedicle screw fixation and transforaminal cage for interbody fusion in a patient
      of Grade 1 Degenerative spondylolisthesis who had an early implant failure, and
      try to assess the possible events leading to it. Case Report: A 53-year-old
      female presented to our outpatient department with low back pain that had
      persisted for a few years. Plain radiographs revealed degenerative Meyerding
      Grade I spondylolisthesis at L5-S1. The patient underwent posterior decompression
      through left-sided laminotomy followed by pedicle screw fixation on the right
      side. Screws were inserted in the pedicle of L5-S1. An optimal hold of the screw
      in the left pedicle of L5 could not be achieved due to the poor quality of bone;
      hence, intraoperatively, the plan was revised from bilateral to unilateral
      pedicle screw fixation. Further, a transforaminal interbody cage was inserted.
      The patient started complaining of severe pain on the 8th post-operative day. X
      ray done on the next day revealed loosening of the rod from the L5 pedicle screw,
      with back out of the insert screw. The patient was subsequently posted for
      revision surgery. During the subsequent follow-up at 6 months, the patient has
      shown significant symptomatic improvement and has resumed her routine daily
      activities. Conclusion: Early rod loosening and migration are a rare phenomenon
      in lumbar pedicle screw fixation. Meticulous and precise pre-operative planning
      and surgical techniques may avert such complications. This case highlights the
      fact that though unilateral fixation is a reported treatment for listhesis, the
      proper case selection is needed. Conditions such as obesity and osteoporosis need
      to be considered, and preferably bilateral fixation should be done in such cases.

PMID- 29181344
TI  - Successful Two-step Correction for Severe Genu Valgum in Ellis-van Creveld
      Syndrome: A Case Report.
AB  - Introduction: Ellis-van Creveld syndrome (EVC) is a very rare genetic disorder
      involving a severe, relentlessly progressive genu valgum deformity of the knee
      and it is usually difficult to correct all of the deformities by elevation of the
      depressed lateral tibial plateau alone. We are reporting one such case treated
      using two-step operative technique (first, gradual correction using Taylor
      spatial frame (TSF) and second, tibia elevation through intra-articular
      osteotomy). Case Report: We report a case of 10-year-old female with severe genu
      valgum in EVC using two-step operative technique. First, performing soft tissue
      release and gradual correction using a TSF. Second, tibia elevation through intra
      articular osteotomy resulted in improved joint congruity. At final follow-up, the
      patient has a good functional result and the Mikulicz line proceeded
      physiologically to the joint center. Conclusion: This two-step technique allowed
      for the correction of the joint architecture and associated complications are
      minimal. For severe genu valgum in EVC, joint congruity is improved by the
      elevation of the anterolateral aspect of the tibia through intra-articular
      osteotomy. Performing soft tissue release followed by gradual correction allows
      for correction of the valgus and external rotation deformities without causing
      neuroparalysis.

PMID- 29181343
TI  - Retained Drain after Anterior Cruciate Ligament Surgery : A Silent Threat to an
      Athlete's Career: A Case Report.
AB  - Introduction: Breaking of surgical drain during the removal and retention of
      broken drain fragment is an avoidable complication. Such a complication brings
      disrepute to the operating team and causes psychological as well as further
      surgical trauma to the patient as a return to the operating room is required many
      a times to remove the retained drain fragment. Case Report: We report a case of
      an undetected retained drain fragment inside the knee joint of a 24-year-old male
      international kabaddi player, who remained asymptomatic for 5 months, when the
      residual drain fragment was removed arthroscopically. No such case has been
      reported earlier in the literature after arthroscopic surgery. Conclusion:
      Retained drain fragment after arthroscopic surgery can stay silent for months.
      Hence, a high index of suspicion should be maintained by surgeons to detect such
      a complication at the earliest. We suggest that every arthroscopic surgeon should
      follow a standard protocol while inserting and removing the drain to avoid this
      mistake.

PMID- 29181345
TI  - Intrapleural Penetration of a Clavicle Fracture: An Indication for Operative
      Fixation.
AB  - Introduction: Clavicle fractures are common injuries treated by orthopedic
      surgeons, with most injuries managed nonoperatively. Operative fixation of
      clavicle fractures is indicated in specific clinical scenarios such as open
      injuries, ipsilateral shoulder trauma, or fractures with associated
      neurovasculature compromise. Operative fixation is not widely accepted for closed
      injuries and is typically reserved for instances of failed closed treatment with
      resultant nonunion or delayed union. Among the complications associated with
      clavicle fractures, pneumothorax has not been commonly reported. We report a case
      of a severely displaced clavicle fracture requiring operative repair through
      plate fixation to achieve union of the fracture as well as resolve the
      pneumothorax. Case Report: A 22-year-old intoxicated male with no past medical
      history was admitted to the trauma bay in stable condition after being involved
      in a motor vehicle accident. On the primary survey, the patient was noted to be
      tachypneic with decreased breath sounds over his right hemithorax. Radiographic
      studies of his chest demonstrated a right proximal third clavicle fracture with
      inferior displacement with associated partial pneumothorax; the patient was also
      noted to have a right femoral shaft fracture. Neurovascular examinations of his
      extremities were normal. A chest thoracostomy tube was inserted and placed under
      suction. Computerized tomography studies later revealed that the fractured
      clavicle had penetrated the pleura and caused the partial lung collapse. The
      patient was initially placed in a sling and underwent intramedullary nailing of
      his femur on the day of presentation. Given the severe displacement of his
      clavicle fracture into the lung tissue resulting in pneumothorax, there was
      significant concern for nonunion and lack of resolution of the pneumothorax. 2
      days after stabilization of his right femur fracture, the patient underwent open
      reduction with internal fixation of his right clavicle. Follow-up radiographs
      showed a healed clavicle fracture and resolved pneumothorax. Conclusion: Closed
      clavicle fractures typically heal uneventfully. Low energy, minimally displaced
      clavicle fractures can be managed nonoperatively, but high energy, significantly
      displaced injuries may require operative repair. Specifically, if these injuries
      result in pneumothorax, physicians shoulder consider operative repair for both
      treatment of the bony defect as well resulting pneumothorax.

PMID- 29181346
TI  - Phalangeal Fracture During Attempted Dupuytrens Release Following Clostridial
      Collagenase Injection: Case Report.
AB  - Introduction: Dupuytren's disease can be a challenging condition for both
      patients and surgeons. Injectable collagen clostridium histolyticum was approved
      for clinical use by the Food and Drug Administration in 2010. A number of side
      effects have been described. In this case report, we present a complication of a
      proximal phalanx fracture which occurred during attempted release post injection.
      To the best of our knowledge, this is the first reported case of this particular
      complication. Case Report: The patient is an 80-year-old right-hand dominant
      retired male with bilateral hand contractures and palmar fibromatosis. His
      medical history is notable for Type II diabetes mellitus and metastatic thyroid
      cancer. The patient underwent Xiaflex injection of the left small finger and
      returned 4 days later for planned release. An appreciable release of the
      contracture was noted; however, there was a concern for plastic deformation of
      the proximal phalanx as a result of the manipulation. X-rays confirmed the
      fracture and apex volar angulation at the base of the proximal phalanx. The
      fracture appeared amenable to non-operative treatment. The patient has been
      followed closely and has had no pain or tenderness at the fracture site and
      minimal swelling. X-rays at 1 week and 1 month showed maintained alignment and
      signs of consolidation at the fracture site. The patient is currently 4-month
      post-fracture, and no further intervention has been pursued. Conclusions: This
      report represents an additional potential complication associated with the use of
      Xiaflex. We recommend judicious use in elderly patients with severe contractures
      and/or multiple comorbidities. It is important to appreciate the possibility of
      this complication at the time of release.

PMID- 29181347
TI  - Pelvic Hydatid Disease: A Case Report and Review of Literature.
AB  - Introduction: Cystic echinococcosis of the bone is rare and difficult to treat
      due to frequent recurrences, especially in certain locations such as ilium and
      hip, where radical surgery is difficult to achieve. Case Report: We present a
      case of a 35-year-old female of the Indian subcontinent who had complaints of
      pain in left hip and limp since 1 year. The first clinical and radiological
      diagnosis was tuberculosis of the hip. However, higher imaging modalities
      revealed the diagnosis of hydatid disease of hip. The patient underwent surgical
      debridement and anti-helminthic chemotherapy. At 3-year follow-up, the patient
      was disease- free. Conclusion: Hydatid disease of the hip and pelvis, although
      rare must be kept in the differential diagnosis of pathologies of hip-like
      tuberculosis. Debridement and excision of hip joint give good functional outcome,
      while also minimizing morbidities that are usually associated the use of custom
      made prosthesis or complex arthroplasty.

PMID- 29181348
TI  - Focal Periphyseal Edema Zone on Magnetic Resonance Imaging in the Greater
      Trochanter Apophysis: A Case Report.
AB  - Introduction: Magnetic resonance imaging (MRI) has been used to identify focal
      bone marrow edema or a focal periphyseal edema (FOPE) zone, in the closing growth
      plates of adolescent knees. Case Report: In the current case, an 11-year-old boy
      reported pain in his left hip. He had been participating in gymnastic classes at
      school, but otherwise, he was not an active athlete. Based on MRI findings, he
      was diagnosed with a FOPE zone in his greater trochanteric apophysis.
      Discontinuity of the cartilaginous growth plate at the FOPE zone was indicative
      of osseous continuity between the metaphysis and apophysis. Conclusion: This case
      suggested that a FOPE zone can occur in a non-weight bearing growth plate and
      through a tethering mechanism at the initial ossification site during skeletal
      growth plate maturation.

PMID- 29181349
TI  - Unstable Pediatric Femur Fractures: Combined Intramedullary Flexible Nails and
      External Fixation.
AB  - Introduction: The treatment of pediatric femur fractures continues to evolve. In
      the past, many of these fractures required prolonged hospitalization in traction.
      More recently, flexible elastic nails have gained popularity. However, length
      unstable and comminuted fractures can present some unique challenges. To avoid
      common complications of elastic nailing in the setting of unstable fractures we
      describe a technique of augmenting this treatment with external fixation for
      cases requiring additional rotational or longitudinal stability. Case Report: A
      series of two patients are described who underwent intramedullary flexible nails
      and external fixation for a closed unstable midshaft femur fracture: An 8-year
      old male that sustained a left periprosthetic femur fracture after a fall on his
      scooter, and a 5-year-old female that sustained a right femur fracture after a
      fall from a wet decking. Both patients had their external fixator removed after 4
      weeks and achieved radiographic and clinical fracture union at 8-week
      postoperatively. Conclusion: Treatment with elastic nails and external fixator
      for unstable pediatric femur fractures is a minimally invasive technique that
      safely provides fracture stability.

PMID- 29181350
TI  - Temporary Fixation Using a Long Femoral-tibial Nail to Treat a Displaced Medial
      Tibial Plateau Fracture in a 90-year-old Patient: A Case Report.
AB  - Introduction: Tibial plateau fractures are complex injuries in the elderly
      population. When traditional methods of fixation are not suitable, an alternative
      method needs to be chosen for a favorable outcome. We demonstrate a previously
      undescribed treatment for displaced tibial plateau fractures in the very elderly
      with poor soft-tissue integrity. Case Report: A 90-year-old woman suffered an
      open, Gustilo Grade IIIA, displaced fracture of the tibial plateau. An
      intramedullary knee arthrodesis, the femoral-tibial nail was used to temporarily
      stabilize her fracture. She was able to weight bear immediately postfixation.
      Conclusion: A long femoral-tibial nail allows favorable fracture and soft tissue
      healing, ease of nursing and immediate full weight-bearing. It shows good promise
      and should be considered as a management option when traditional methods are not
      applicable in select patients.

PMID- 29181351
TI  - Cerclage Wiring as an Adjunct for the Treatment of Femur Fractures: Series of 11
      Cases.
AB  - Introduction: Cerclage wiring has been used in the past for osteosynthesis of
      femoral fractures. However, the technique went into disrepute as extensive soft
      tissue dissection, and periosteal stripping increased the risk of bone necrosis
      and delayed union. Advent of new instrumentation and minimally invasive technique
      has significantly reduced these complications. In spite of the limited
      indications for its application, reduction and stabilization with cerclage wiring
      can supplement osteosynthesis especially in spiral or oblique fracture morphology
      or those with a butterfly fragment instead of interfragmentary screw fixation.
      This series attempts to describe the feasibility and evaluate outcomes of
      cerclage wiring as an adjunct to osteosynthesis and reestablish its place in
      reduction and fixation of femur fractures. Case Report: This is a retrospective
      case series of patients (January 2011 to October 2015) in whom cerclage wiring
      was used as an adjunct to osteosynthesis of primary and periprosthetic fractures
      of femur. Patient demographics, number of wires used, implant used for
      osteosynthesis, number of days to union, union rate and complications were
      recorded and analyzed. The patients were followed up for a minimum of 6 months.
      11 patients (7 female and 4 male) with a mean age of 67.10 +/- 21.64 years were
      studied. The number of patients with intertrochanteric, subtrochanteric,
      diaphyseal, and periprosthetic fractures of the femur was two, five, one, and
      three, respectively. Internal fixation was done with plates in six and
      cephalomedullary nails in five patients. Mean total number of wires used was 2.10
      +/- 0.70. Mean duration of follow-up was 15.91 +/- 10.03 months. Union was
      achieved in all cases with a mean duration of 86.63 +/- 22.44 days. There were no
      complications in our study. Conclusion: Cerclage wiring technique helps to
      achieve stable reduction of femoral fractures which can then be supplemented with
      a nail or a plate. The minimally invasive technique and instrumentation offer the
      advantage of minimal soft tissue dissection, and the procedure is associated with
      excellent outcomes without any major complications.

PMID- 29181352
TI  - A Case Report of Dual Incision Technique for Total Femur Arthroplasty as a
      Salvage Procedure in Infected Non-Unions.
AB  - Introduction: Total femur arthroplasty (TFA) is a rare salvage limb procedure
      which serves as an effective alternative to limb amputation. Most commonly, it is
      indicated for oncologic orthopedic cases, and very few cases of a purely
      traumatic history for TFA have been documented. The decision to perform this
      complex procedure involves paying careful attention to reconstructive needs and
      functional expectations of the patient. Alternatives to this procedure are quite
      detrimental and include hip disarticulation and above-the-knee amputation. Case
      Report: A 66-year-old woman with a history of hypertension, and parkinsonism was
      brought into the outpatient department of a tertiary care hospital. She has
      undergone a procedure for proximal femur nailing on her left hip in 2013 due to a
      trauma-related fracture. However, after the development of a series of
      complications, she underwent revision surgery on her left hip 6 times by
      different surgeons. This included surgeries for implant removal and fixation of a
      custom-made bipolar hemi-replacement hip, followed by a cemented bipolar hip hemi
      replacement with plating and cerclage wires followed by infection, the treatment
      of which entailed implant removal and placement of an antibiotic cement. This was
      followed by a long stem constrained cemented total hip arthroplasty which also
      failed. The surgeon then made the decision to perform a TFA. 12-month follow-up
      post-operatively showed neither peri-prosthetic infection or inflammation nor any
      leg length discrepancy. The functional outcome on lower extremity function scale
      showed improvement from 0 pre-operatively to 31 at 12-month follow- up.
      Conclusion: TFA serves as a viable technique for salvage of the lower extremity
      in cases of infected non-unions. However, a thorough evaluation of the particular
      case in the hand should be made before reaching a conclusion.

PMID- 29181353
TI  - Pyomyositis of Gluteus medius: A case report and review of the literature.
AB  - Introduction: We present a case of 12 year old boy presented with right hip pain,
      fever and antalgic gait. Inflammatory markers were raised at presentation. The
      pelvic radiograph and ultra sound scan of right hip joint did not detect any
      abnormality. The Magnetic Resonance Imaging (MRI) scans revealed inflammatory
      oedema in the right gluteus medius muscle. He was treated with intravenous
      Flucloxacillin for 10 days and later 6 weeks of oral Flucloxacillin. At the 6
      weeks follow up patient was asymptomatic with normal gait. MRI at 6 weeks did not
      show any fluid collection in gluteus medius. Conclusion: Pyomyositis is rare in
      temperate countries. It must be considered as one of the differential diagnosis
      in a child presenting with hip pain, fever and raised inflammatory markers.

PMID- 29181354
TI  - Central Chest Pain - An Atypical First Presentation.
AB  - Introduction: The diagnosis of thoracic spondylodiscitis is challenging, given
      that it is a rare entity in itself and when unusual symptoms such as central
      chest pain predominate on presentation, it may pose a serious diagnostic
      challenge. Case Report: A 54-year-old patient presented to accident and emergency
      with central chest pain and elevated inflammatory markers (C- reactive protein
      [CRP]: 21 mg/L). Following exclusion of life-threatening cardiac causes, he was
      discharged home with analgesia and no formal diagnosis. Over the course of the
      subsequent 6 weeks, he presented to his general practitioner on two different
      dates with worsening chest pain alongside a new symptom of back pain and
      progressively rising inflammatory markers. At 6 weeks, he presented back to the
      emergency department with clinical signs of sepsis, mid-thoracic tenderness with
      weakness and altered sensation to his legs. The CRP was raised at 297 mg/L. In
      view of these symptoms, a contrast magnetic resonance imaging scan was performed
      which revealed destruction of the sixth and seventh disc space with high signal
      intensity on T2 and short tau inversion recovery images in T6 and T7. Blood
      cultures were shown to have grown Staphylococcus aureus, and the patient was
      subsequently treated with combined intravenous antibiotics (flucloxacillin) and
      oral antibiotics (rifampicin) for 15 weeks resulting in complete resolution of
      his symptoms. Conclusion: Our case report highlights the need for a high index of
      suspicion of spondylodiscitis in patients presenting with central chest pain,
      unresolving back pain and elevated inflammatory markers especially in the absence
      of any other formal diagnosis.

PMID- 29181355
TI  - Group B Streptococcal Prosthetic Knee Joint Infection Linked to the Consumption
      of Raw Fish.
AB  - Introduction: Group B Streptococcal (GBS) prosthetic joint infections (PJI) are
      rare, accounting for only 4.6-6% of primary and revision total knee replacements
      (TKRs). In 2015, there was an outbreak of GBS infections in Singapore with an
      association confirmed between consumption of Chinese-style raw fish dishes
      (snakehead fish, Asian bighead carp) and GBS infection, Type III GBS ST283
      strain, affecting more than 200 patients in Singapore. This outbreak is the
      largest of its kind in the world and also the first time that foodborne
      transmission of GBS has been proven. We present the first reported case in the
      literature of a confirmed PJI in a TKR related to foodborne transmission of GBS
      through consumption of raw fish (Snakehead fish). Case Report: Our patient is a
      66-year-old Chinese female admitted with a 24-h history of acute right knee pain
      and swelling with associated fever in the context of consuming raw fish porridge
      3 days before the onset of her symptoms. She had a TKR performed in the same knee
      7 years before this presentation. Her GBS PJI was confirmed on both blood and
      intraoperative tissue/fluid cultures during the outbreak of GBS infections in
      Singapore. This was managed with debridement, polyethylene liner change,
      retention of metal prosthesis, and culture-directed antibiotics with good
      outcomes. Conclusion: Snakehead fish is a popular dish in the Asian community as
      a traditional remedy to promote wound healing after surgery. Our paper highlights
      the link between raw fish consumption and invasive GBS causing PJIs. This can
      occur in healthy adults, even in the absence of gastrointestinal symptoms,
      despite being a foodborne transmission. Our paper also highlights that GBS PJIs
      can be managed with debridement, antibiotic therapy, and implant retention with
      good outcomes in the setting of acute hematogenous infection. We recommend the
      inclusion of raw fish consumption on history taking in the workup of suspected
      PJIs and counseling patients preoperatively on the risk of GBS PJIs with the
      consumption of raw fish dishes (snakehead fish and Asian bighead carp) to
      mitigate unnecessary PJI risk.

PMID- 29181356
TI  - A Case of 3-month-old Neglected Elbow Dislocation Managed by Open Reduction and
      Cruciate Ligament Reconstruction Using Tendon Graft.
AB  - Introduction: Old neglected posterior type of elbow dislocations is not very
      common and generally requires open reduction. It was usually treated with open
      reduction and K-wire stabilization. We did a newer method in which in addition
      cruciate type ligament reconstruction; we have reconstructed lateral ulnar
      collateral ligament (LUCL) and UCL (medial collateral ligament) using
      semitendinosus graft. This allowed extra stability and early mobilization of the
      elbow joint. Authors report 3-month-old neglected posterior type of elbow
      dislocation without any fracture. Case Report: A 42-year-old male presented with
      pain and tenderness with deformity of the left elbow joint and inability to move
      the elbow joint after he fell down since 3 months. There was no neurovascular
      deficit. Radiological examination confirmed posterior dislocation of elbow joint
      without any fracture. The patient is managed by open reduction and cruciate
      ligament reconstruction of elbow joint using autologous semitendinosus graft.
      Conclusion: Open reduction with cruciate ligament reconstruction provides
      excellent stability for early mobilization of old neglected elbow dislocation.

PMID- 29181357
TI  - Aspergillus Osteomyelitis of the Ribs in Immunocompetent Hosts: Report of Two
      Rare Cases.
AB  - Introduction: Osteomyelitis is rarely caused by fungi, most common among them
      being Candida. Aspergillus is a rare cause of fungal osteomyelitis mimics
      tuberculous osteomyelitis. Aspergillus osteomyelitis (AO) of the ribs is
      relatively uncommon, with an incidence rate of only 9% among all reported cases
      of AO. With mortality rates of almost 25%, AO is on the rise attributed to
      increasing numbers of immunocompromised individuals. There are very few case
      reports of AO of ribs in immunocompetent individuals. We report two such cases.
      Case Report: Case 1: A 51-year-old male developed spontaneous chest pain along
      right costal margin with a low-grade fever. High-resolution computed tomography
      chest revealed osteomyelitis of anterolateral chest wall. He did not improve with
      empirical antitubercular therapy, and subsequent debridement showed polymicrobial
      pyogenic infection which was managed with appropriate antibiotics elsewhere.
      Samples were not sent for fungal culture. He presented to us 3 months later, and
      surgical debridement showed growth of Aspergillus flavus which was managed with
      oral voriconazole. The lesion healed with no recurrence at 24-month follow-up.
      Case 2: A 40-year-old male presented to our institute with left-sided chest pain,
      low-grade fever, and loss of appetite. There was a history of injury with a sharp
      piece of wood 2 years earlier. Magnetic resonance imaging defined the lesion
      which was biopsied under ultrasound guidance. Cultures grew A. flavus which was
      treated with oral voriconazole. He had complete clinical improvement at 16-month
      follow-up. Conclusion: More number of AO cases are being reported in
      immunocompetent individuals. Variability in clinical picture, rarity,
      misdiagnosis, empirical therapy, and failure to send deep tissue samples for
      fungal cultures are some of the reasons for the high mortality rates. It is
      paramount in today's scenario of atypical presentations, to obtain deep tissue
      for all cultures including fungal culture and histopathology, either surgically
      or under image guidance to achieve good clinical outcomes. Our study highlights
      that following the strict protocol of obtaining tissue for fungal culture,
      systemic antifungal therapy, and surgical debridement where necessary can help to
      diagnose and treat this rare pathology and ensure the good clinical outcome.

PMID- 29181358
TI  - A Case Report: Upper Thoracic Chance Fracture with Monoplegia... An Unusual
      Presentation!
AB  - Introduction: Chance fractures, the horizontal splitting vertebral fractures
      caused by flexion distraction mechanism, are inherently unstable fractures. These
      fractures can land up with significant visceral injuries. There are most commonly
      seen at thoracolumbar junction or in lumbar spine due to their high mobility.
      These fractures are extremely rare in the thoracic spine due to the rigidity of
      thoracic spine rendered by attachment of ribs. Furthermore, the level of injury
      makes neurological complications even graver. Case Report: We present a case of a
      road traffic accident with right lower limb monoplegia. On careful examination, a
      thin transverse fracture line was noticed in D5 vertebral body, and magnetic
      resonance imaging revealed posterior ligamentous disruption extending in line
      with the transverse fracture line in D5 vertebral body which confirmed the
      diagnosis of a Chance fracture. Fracture was stabilized by pedicle screw fixation
      from D4 to D7 level, and decompression was done at D5 level. By the end of 7
      months, patient regained Grade 4 power in the right hip and knee joints, with
      Grade 5 power in the right ankle and great toe. Conclusion: Chance fractures in
      thoracic region are extremely rare. A clinician should have a high index of
      suspicion as these fractures can be notorious when it comes to presentation on
      plain X-ray. These being inherently unstable fractures, posterior instrumented
      stabilization with decompression in patients with neurodeficit gives good
      results.

PMID- 29181359
TI  - Articular Reconstruction using Subchondral Cementation and Threaded Kirschner
      wires in Giant Cell Tumor: A Novel Technique.
AB  - Introduction: Giant Cell Tumor(GCT) is one of an infrequently encountered tumor
      by orthopaedic surgeons in clinical practice. It is described as 'locally
      malignant' tumor found in epimetaphyseal region of long bones, peculiarly around
      knee. We present a case of a solitary, benign Campanacci Grade 2 GCT in right
      lateral femoral condyle in 38 year old female and our treatment. Case Report: A
      38 year old female presented to our outpatient department with chief complaint of
      constant, moderate pain in right knee increasing in duration since 3 months. No
      history of precedent trauma. Radiological imaging with radiographs showed
      suspicious lytic lesion in lateral femoral condyle. MRI scan was done.On biopsy,
      histopathological evaluation showed presence of characteristic multinucleated
      giant- cells. After confirmation, tumor en bloc resection was done, followed by
      chemical cauterization with 5 % phenol. Articular margins were realigned under
      direct vision and fixed with 1.8 mm threaded K wires. PMMA cementing in bone
      defect was done after achieving adequate hemostasis. At two years follow-up,
      patient had good result in terms of pain, knee range of motion and weight
      bearing. Conclusion: Combination treatment of radical curettage, phenol
      irrigation, electrocautery and cementation is effective in preventing local
      recurrence. This can replace en bloc resection with a wide margin. Using
      subchondral threaded Kirschner wires to maintain articular margins is cheap
      alternative to costly implants in economically underprivileged patients.

PMID- 29181360
TI  - Tension Band Wiring Is As Effective As A Compression Screw In A Neglected, Medial
      Maleolus Non-Union: A Case-Based Discussion & Literature Review.
AB  - Introduction: Isolated, neglected medial malleolus nonunion cases are a rare
      entity in orthopedic literature. All studies (except one) have described the use
      of compression screws (with or without plates) for medial malleolar nonunion
      management. In acute fractures, tension band wiring (TBW) has shown excellent
      results both in biomechanical and in clinical studies. On the contrary, it has
      seldom been used in nonunion or in neglected cases. Case Report: We describe a 6
      month-old neglected medial malleolus gap nonunion case who presented with
      progressive pain and limp. TBW with a monoblock, inlay, tricortical, and iliac
      crest bone graft for the defect was performed. The fracture united within 12
      weeks and patient went back to his normal work routine; on the latest follow-up
      at 3 years, the patient was asymptomatic with no clinicoradiologic signs of
      secondary osteoarthritis of the ankle joint. Conclusion: TBW may be better than
      screw fixation in the management of medial malleolus nonunion as it is
      technically straightforward and cost-effective, can provide equal or more
      compression than a screw; it does not damage the sandwiched inlay bone graft, and
      the amount of compression is surgeon-controlled. It is also more suitable for
      fractures with small distal fragments and/or osteoporosis.

PMID- 29181361
TI  - Insufficiency Fractures at Unusual Sites: A Case Series.
AB  - Introduction: Insufficiency fractures (IFs) are a subtype of stress fractures
      commonly associated with osteoporosis and Vitamin D deficiency. These
      nontraumatic fractures often occur in the pelvis and spine, but the involvement
      of other unusual sites is also not very uncommon. Plain radiographs and magnetic
      resonance imaging scan are the most commonly used imaging modalities for the
      diagnosis of IF. Case Report: We are presenting a series of five cases of IFs at
      unusual sites, along with a detailed literature review on this individual. A 50
      year-old male patient with chronic kidney disease presented with both femoral
      neck and right lesser trochanter IF which was managed with cannulated screws. A
      53-year-old male patient on steroid presented with sternum IF. A 26-year-old male
      patient presented with Vitamin D deficiency and accessory navicular IF. A 60-year
      old female on bisphosphonate therapy came with bilateral femoral shaft fracture.
      All these three patients were managed conservatively. Another 62-year-old male
      patient with rheumatoid arthritis presented with sacrum IF which was managed with
      cannulated screw fixation. Conclusion: IFs are a subtype of stress fractures
      commonly associated with osteoporosis and Vitamin D deficiency. A good clinical
      examination along with proper radiological investigation facilitates early
      diagnosis of IF in the osteoporotic bone. An early diagnosis helps in deciding
      the definitive course of treatment and to obtain a good result. An undisplaced
      fracture can be managed nonoperatively by treating the underlying medical cause,
      but fractures at the risk of displacement or a displaced fracture may need
      operative treatment.

PMID- 29181362
TI  - Erratum: Author's name correction.
AB  - [This corrects the article on p. 5 in vol. 6, PMID: 27299113.].

PMID- 29181363
TI  - PREVALENCE OF BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER IN AFRICANS AND
      AFRICANS IN THE DIASPORA.
AB  - Background: There have been several publications on population or community
      prevalence of benign prostatic hyperplasia and prostate cancer from various
      countries and races but few reports are from Africa on Africans. Aim: A review on
      the prevalence of benign prostatic hyperplasia and prostate cancer in Africans
      and other races. Methodology: The current literature on prevalence of benign
      prostatic hyperplasia (BPH), prostate cancer (PC), and benign prostatic
      hyperplasia co-existing with prostate cancer in Africans and other races is
      reviewed. Results: Benign prostatic hyperplasia (BPH) prevalence in Ghana is
      responsible for 60% acute retention of urine and 28.6% of haematuria. Worldwide
      prevalence of BPH varies from 20 - 62% in men over 50 years and this includes
      USA, UK, Japan and Ghana. Reports from South Africa indicate prevalence of over
      50% in adult males of 60 years. BPH co-existing with PC - Reports from USA, UK
      and Japan and Ghana reveal moderate association of BPH and PC. The co-existence
      of PC in patients being treated for BPH is 3 - 20% Prostate Cancer prevalence -
      There is high prevalence in USA, Scandinavian Countries, African Americans (AA)
      and Caribbean blacks. Ghana, Trinidad & Tobago have reported high prevalence of 6
      -10% in men aged 50 years and above but others reported low prevalence in
      Africans from Africa. The low reporting from Africa of 10 - 40:100,000 is
      attributable to under reporting, absence of PSA screening/testing, lack of
      reliable cancer registries and poor medical facilities. Economic Costs of BPH and
      PC: BPH in the USA national direct costs are estimated at U$4Billion and
      individual costs of US$1536 annually. In Ghana, individual costs for BPH
      medications range from US$300 - 550 per year and cost for simple
      prostatectomy/TURP is estimated at US$1100. For prostate cancer, individual
      direct costs from Europe range from 6,575 - 12,000 euros, L2818.00 UK and over
      U$12,000 - 20,000 in USA per annum. In Ghana, individual direct costs ranges, for
      radical prostatectomy and external beam radiotherapy US$1250 - 1500, for
      brachytherapy 9,000 Euros, for hormonal therapy US$1600 - 3200) per year and
      US$510 for orchidectomy. Conclusion: Recent evidence although sparse indicate
      there is high prevalence of BPH and PC in Africans and men of African descent in
      diaspora, the low prevalence of BPH and PC reported from some African countries
      is likely to under reporting and future prevalence studies both in the living and
      deceased are recommended to reveal the true prevalence of BPH and PC in Africans
      though screening for PC in the living remains controversial.

PMID- 29181365
TI  - A COMMUNITY-BASED PREVALENCE OF PRESBYOPIA AND SPECTACLE COVERAGE IN SOUTHWEST
      NIGERIA.
AB  - Background: The use of population-based method to assess the prevalence of
      presbyopia and spectacle use is few even though it is more reliable compared to
      the commoner hospital based studies. This study was carried out to determine the
      need for spectacle services in our coverage area. Aim: To determine the
      prevalence of presbyopia among adults of 30 years old and above in Sagamu local
      government area of Ogun state, South-West, Nigeria. Design: The study was a
      population based descriptive and cross-sectional design. Setting: The study was
      carried out using a multistage cluster random sampling with probability
      proportional to size of regular adult residents of Sagamu Local Government area,
      Sagamu, Ogun state, Nigeria. Materials and Methods: Examination of respondents
      included administration of semi-structured interviewer assisted questionnaire and
      distance visual acuity measurement with or without pinhole at 6 meters using the
      Snellen's charts. Automated refraction with subjective refraction was carried out
      in all participants with presenting visual acuity (PVA) worse than 6/9 but with
      an improvement with pinhole. Near assessment was done at 40cm with the distance
      correction in place if required. Ocular examination was also carried out in all
      participants that had refraction including pupillary dilatation when indicated.
      Results: The prevalence of presbyopia was 80.9%. There was an increasing
      prevalence with age (p<0.001) with a 100% prevalence in the >=80 years age group.
      The mean add requirement was +2.24DS. The met presbyopic need was 22.9% and the
      unmet need 58%. The presbyopic spectacle coverage was 28.4% which was positively
      associated with younger age (p=0.034), attaining at least secondary school
      education (p<0.001), and living in an urban area (p<0.001). Conclusion: The
      prevalence of presbyopia is high in this community and found in persons younger
      than 40 years and the spectacle coverage for the population is low with a high
      unmet spectacle need. There is a need to provide near vision spectacles to a
      large proportion of residents in the community.

PMID- 29181364
TI  - MANAGEMENT OF PROSTATE CANCER IN ACCRA, GHANA.
AB  - Introduction: Africans living with prostate cancer in Africa face problems of
      early diagnosis and appropriate treatment. Aim: To study the clinical incidence
      of prostate cancer, risk factors, TNM stage, their management and outcomes.
      Methods: A prospective study of Prostate Cancer cases managed at Korle Bu
      Teaching Hospital and hospitals in Accra, diagnosed by history, abnormal PSA/DRE,
      physical examination and histologically confirmed by biopsy from 2004 to 2013 was
      carried out. The cases were TNM staged and managed by approved protocol. Results:
      There were 669 cases with a mean age 70+/-0.045SE years, median Gleason Score of
      7, organ confined Prostate Cancer(PC) in 415(62%), locally advanced in 167(25%)
      and metastatic Prostate Cancer in 87(13%) cases. The cases were followed for
      median of 10 months to >= 84 months. Organ confined cases were managed by:
      Radical Prostatectomy (RP) 92 (13.8%) with a mortality of 0.3%; brachytherapy 70
      (10.5%) with a mortality of 0.1% and External Beam Radiotherapy (EBRT) 155 (23%)
      with a mortality 0.7%. In all, 98 men constituting (14.1%) cases with a mean age
      of 75+0.25SE years, life expectancy <10 years were treated by hormonal therapy
      with a mortality of 1.7%. Twenty cases who were for active surveillance (GS6),
      PSA <10ng/ml, life expectancy <10 years later all opted for EBRT. Locally
      advanced cases 25% all had neoadjuvant hormonal therapy then Brachytherapy in 3
      (0.4%) mortality 0.15% and EBRT in 64 (9.5%), mortality 0.59%. Hormonal therapy
      was given in 100 (15%) locally advanced cases, mortality 5%. Metastatic prostate
      cancer cases (13%) were managed by hormonal therapy, mortality 6%. Conclusion:
      Improved facilities and dedicated skilled teams led to a significant rise in
      proportion of organ confined Prostate Cancer from 15.3% to 62% curable by Radical
      Prostatectomy, brachytherapy or EBRT with longer disease free survival.

PMID- 29181366
TI  - ANAESTHETISTS' ATTITUDES AND PRACTICE OF INFORMED CONSENT IN NIGERIA.
AB  - Background: Informed consent is an integral part of a surgical and anaesthetic
      procedure, failure to obtain it may result in grave medico-legal implications.
      Aim: To determine the attitudes of Nigerian anaesthetists to informed consent.
      Methodology: The study population included physician anaesthetists who attended a
      continuous medical education programme in November 2015. The target was to cover
      over 50% of anaesthetists by convenience sampling. The responses to the questions
      were recorded and descriptive statistics were employed to calculate the various
      qualitative variables under study. Results: Fifty-six respondents were analysed,
      the majority were in the age group 31-40 years (37.5%), consultants were 51.79%,
      and males constituted 75%. The respondents agreed that the main purposes of
      informed consent included a need to improve the doctor/patient relationship in
      36(64.29%), inform the patient about the desired benefits of the procedure in
      32(57.14%), provide the doctor with greater protection against medical litigation
      in 32(57.14%), and to respect the patient's right of autonomy in 30(53.57%). The
      general consensus among the respondents was that the anaesthetist should explain
      to the patient what the procedure entails 40(71.43%), what the procedure aims to
      achieve and additional procedures that are likely to be necessary to the patient
      41(73.21%). It was also agreed that there should be disclosure of all major
      risks/complications with incidence >1/20 in 29(51.79%) respondents, incidence
      >1/100 in 20(35.71%), incidence >1/1000, and incidence >1/10000 were 17(30.36%).
      The respondents who agreed that it is necessary to take consent before performing
      surgery or anaesthesia on patients and explained the procedure to patients were
      48(85.71%). Conclusion: We determined that informed consent was an integral part
      of a surgical procedure. which helped to improve doctor/patient relationship,
      respected the patient's right of autonomy and provided the surgeon and
      anaesthetists with greater protection against medical litigation. It is paramount
      to disclose all major risk and complications. However, few anaesthetists
      19(33.93%) obtain informed consent from their patients before epidural labour
      analgesia.

PMID- 29181367
TI  - RADIOTHERAPY TREATMENT OF KELOIDS IN IBADAN.
AB  - Background: The management of keloids has posed a difficult challenge to the
      patient, surgeon and radiation oncologist due to its high recurrence rate
      following treatment. Post-operative radiotherapy has been used to improve outcome
      of treatment by reducing recurrence. However, this is difficult in Africa where
      there are few Radiotherapy machines and some of those available are not the
      standard for the treatment for superficial tumours and lesions like keloids. Aim:
      To assess the pattern of presentation, treatment and outcomes in patients with
      keloids. Study design: A retrospective cross-sectional study. Setting: University
      College Hospital, Ibadan, Nigeria. Methodology: Records of all patients treated
      for keloids over a 25-year period were retrieved and their demographics, site and
      number of keloids, radiation treatment and outcome. The data obtained were
      analysed using the SPSS version 22. Results: In all, 172 cases were seen within
      the period with a male preponderance (57%), i.e. male: female ratio of 1.3:1. The
      age range was 12 - 73 years with a mean of 28.7 +/-14.53 years with 42.4% of the
      patients in the 20- 29 years bracket. Also, 69% of patients had a single keloid
      and the ears (35%) were the commonest sites in 35% of cases, the face (28.6%),
      the trunk (18.6%) and the neck (8.7%).All the patients had surgical excision
      followed by radiation therapy within 72 hours of surgery. They all received 12Gy
      in 2 fractions over 2 weeks except one that had 25Gy in 10 alternate daily
      fractions due to the large size of the tumour. There was no documented
      complication during and following treatment. The recurrence rate was 14.53%.
      Conclusion: Immediate postoperative radiotherapy of keloids is safe with good
      outcome and a low recurrence rate.

PMID- 29181368
TI  - CEPHALOMETRIC ASSESSMENT OF HYOID BONE POSITION IN NIGERIAN PATIENTS WITH
      BIMAXILLARY INCISOR PROCLINATION.
AB  - Background: Hyoid bone though constitute a small proportion of the human
      skeleton, its importance in relation to other facial structures cannot be
      overemphasized. Several studies have reported on hyoid bone position in relation
      to various types of malocclusion, however, to our knowledge, there has been no
      study on the relationship between the hyoid bone and bimaxillary incisor
      proclination. Aim: The aim of this study was to assess the relative position of
      hyoid bone in individuals with and without bimaxillary incisor proclination as
      well as other related demographic factors. Methodology: This was a comparative
      retrospective study of lateral cephalometric radiographs of orthodontic patients
      aged 12 to 40 years from two study locations (Ile-Ife and Lagos, Nigeria). Thirty
      randomly selected radiographs of patients with bimaxillary incisor proclination
      were compared with 30 radiographs of related cases with normal incisor
      relationship. These radiographs were manually traced using established
      cephalometric landmarks and analysed using SPSS 16. Independent t-test was used
      to compare mean values and statistical significant level was set as p<0.05.
      Results: Most of the linear and angular dental/skeletal measurements in relation
      to hyoid bone position showed no significant differences within the compared
      groups. Hyoid bone position (H-TV) was found to be more anteriorly located in
      male (p=0.02) and in bimaxillary incisor proclination (p=0.004) patients than
      their female and normal incisor relationship groups respectively. Similarly,
      there was a highly statistically significant difference in linear measurement of
      the lower incisor tip to hyoid bone position (H-LIT) between the adolescent and
      young adult groups (p=0.01). Conclusion: The hyoid bone position in male and
      bimaxillary incisor proclination subjects were more anteriorly located when
      compared with female and normal incisor relationship groups respectively.
      Similarly, the distance between the hyoid bone position and the lower incisor tip
      was longer in young adults than the adolescent group.

PMID- 29181370
TI  - Peer-Reviewed Abstracts of Scientific Paper Presentation at The 56th Annual
      Conference of The West African College of the Surgeons at Yaounde, Cameroun 15th 
      19th February 2016 Contd.

PMID- 29181369
TI  - ORBITAL AND ADNEXAL LYMPHOMAS AMONG ADULT PATIENTS IN GHANA.
AB  - Background: Non Hodgkin's lymphomas (NHLs) present variously in different ethnic
      communities. Orbital and adnexal disorders have been reported among NHLs in
      Africa. They can involve the orbit, the eyelid, the conjunctiva, alone or in
      combinations. To our knowledge there are no reports in the literature about the
      clinical presentation of lymphomas in Ghana. Aim: To explored orbital and adnexal
      disorders among adult patients attending the Korle-Bu Teaching hospital, Accra.
      Methodology: Histological case notes of patients reporting to the orbital clinic
      of Korle-Bu Teaching Hospital, Eye Department from November 2004 to October 2016
      with orbital and adnexial lympho-proliferative tumors were retrieved.
      Histopathology was performed at Sheffield Teaching hospital. Data collected
      included age, sex, symptoms at presentation and anatomic site of involvement.
      Histology and immune histochemistry data were generated. Results: A total of 18
      patients were examined and entered into the study. The male to female ratio was
      1.25:1. Twelve patients (70.6) presented with proptosis and 14 (77.8%) had
      orbital involvement. Two patients had isolated eyelid disease. Of those with
      orbital disease, three had simultaneously upper eyelid involvement. Out of the 18
      cases, 11 (61.1%) were mucosa-associated lymphoid tissue (MALT) lymphomas. Only
      males 40 years and above were affected, compared with females who presented at
      any age. Patients above 60 years reported early (i.e. <3 months) compared with
      patients below 40 years who mostly reported after 1 year. Conclusion: This study
      reports pattern of epidemiological and clinical presentation of orbital and
      adnexal lymphomas as seen in Ghana, West Africa. Though there were some
      variations in the clinical presentation the histological subtypes represented
      seem to be similar to those reported in other parts of the world.

PMID- 29181371
TI  - BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER IN AFRICANS AND AFRICANS IN THE
      DIASPORA.

PMID- 29181372
TI  - The new era of cancer immunotherapy: what can molecular imaging do to help?

PMID- 29181373
TI  - Prevalence of Anxiety and Depression in Patients with Inflammatory Bowel Disease.
AB  - Background: Inflammatory bowel disease (IBD) patients are not routinely screened
      for depression and anxiety despite knowledge of an increased prevalence in people
      with chronic disease and negative effects on quality of life. Methods: Prevalence
      of anxiety and depression was assessed in IBD outpatients through retrospective
      chart review. The presence of anxiety and/or depression was determined using the
      Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 self-report
      questionnaires or by diagnosis through psychiatric interview. Patient
      demographics, disease characteristics, and medication information were also
      collected. Multivariable analysis was used to determine associations between
      patient factors and depression and anxiety. Results: 327 patient charts were
      reviewed. Rates of depression and anxiety were found to be 25.8% and 21.2%, with
      30.3% of patients suffering from depression and/or anxiety. Disease activity was
      found to be significantly associated with depression and/or anxiety (p = 0.01).
      Females were more likely to have anxiety (p = 0.01). Conclusion: A significant
      proportion of IBD patients suffer from depression and/or anxiety. The rates of
      these mental illnesses would justify screening and referral for psychiatric
      treatment in clinics treating this population. Patients with active disease are
      particularly at risk for anxiety and depression.

PMID- 29181374
TI  - Malignancy-Induced Hypercalcemia-Diagnostic Challenges.
AB  - Hypercalcemia in children is a rare metabolic finding. The clinical picture is
      usually non-specific, and the etiology includes several entities (metabolic,
      nutritional, drug-induced, inflammatory, cancer-associated, or genetic) depending
      on the age at presentation, but severe hypercalcemia is associated mainly with
      malignancy in childhood and sepsis in neonates. Severe parathyroid hormone (PTH)
      suppressed hypercalcemia is challenging and requires multidisciplinary diagnostic
      and therapeutic approaches to (i) confirm or rule out a malignant cause, (ii)
      treat it and its potentially dangerous complications. We report a case of severe
      and complicated PTH-independent hypercalcemia in a symptomatic 3-year-old boy.
      His age, severity of hypercalcemia and its complicated course, and the first
      imaging reports were suggestive of malignancy. The first bone and kidney biopsies
      and bone marrow aspiration were normal. The definitive diagnosis was a malignant
      induced hypercalcemia, and we needed 4 weeks to assess other differential
      diagnoses and to confirm, on histopathological and immunochemical base, the
      malignant origin of hypercalcemia. Using this case as an illustrative example, we
      suggest a diagnostic approach that underlines the importance of repeated
      histology if the clinical suspicion is malignancy-induced hypercalcemia.
      Effective treatment is required acutely to restore calcium levels and to avoid
      complications.

PMID- 29181375
TI  - Editorial: Reducing Oral Health Disparities: Social, Environmental and Cultural
      Factors.

PMID- 29181376
TI  - Automated Solid-Phase Protein Modification with Integrated Enzymatic Digest for
      Reaction Validation: Application of a Compartmented Microfluidic Reactor for
      Rapid Optimization and Analysis of Protein Biotinylation.
AB  - Protein modification by covalent coupling of small ligands or markers is an
      important prerequisite for the use of proteins in many applications. Well-known
      examples are the use of proteins with fluorescent markers in many in vivo
      experiments or the binding of biotinylated antibodies via biotin-streptavidin
      coupling in the frame of numerous bioassays. Multiple protocols were established
      for the coupling of the respective molecules, e.g., via the C and N-terminus, or
      via cysteines and lysines exposed at the protein surface. Still, in most cases
      the conditions of these standard protocols are only an initial guess.
      Optimization of the coupling parameters like reagent concentrations, pH, or
      temperature may strongly increase coupling yield and the biological activity of
      the modified protein. In order to facilitate the process of optimizing coupling
      conditions, a method was developed which uses a compartmented microfluidic
      reactor for the rapid screening of different coupling conditions. In addition,
      the system allows for the integration of an enzymatic digest of the modified
      protein directly after modification. In combination with a subsequent MALDI-TOF
      analysis of the resulting fragments, this gives a fast and detailed picture not
      only of the number and extent of the generated modifications but also of their
      position within the protein sequence. The described process was demonstrated for
      biotinylation of green fluorescent protein. Different biotin-excesses and
      different pH-values were tested in order to elucidate the influence on the
      modification extent and pattern. In addition, the results of solid-phase based
      modifications within the microfluidic reactor were compared to modification
      patterns resulting from coupling trials with unbound protein. As expected,
      modification patterns of immobilized proteins showed clear differences to the
      ones of dissolved proteins.

PMID- 29181377
TI  - Mitochondria As Sources and Targets of Methane.
AB  - This review summarizes the current knowledge on the role of mitochondria in the
      context of hypoxic cell biology, while providing evidence of how these mechanisms
      are modulated by methane (CH4). Recent studies have unambiguously confirmed CH4
      bioactivity in various in vitro and in vivo experimental models and established
      the possibility that CH4 can affect many aspects of mitochondrial physiology. To
      date, no specific binding of CH4 to any enzymes or receptors have been reported,
      and it is probable that many of its effects are related to physico-chemical
      properties of the non-polar molecule. (i) Mitochondria themselves can be sources
      of endogenous CH4 generation under oxido-reductive stress conditions; chemical
      inhibition of the mitochondrial electron transport chain with site-specific
      inhibitors leads to increased formation of CH4 in eukaryote cells, in plants, and
      in animals. (ii) Conventionally believed as physiologically inert, studies cited
      in this review demonstrate that exogenous CH4 modulates key events of
      inflammation. The anti-apoptotic effects of exogenously administered CH4 are also
      recognized, and these properties also suggest that CH4-mediated intracellular
      signaling is closely associated with mitochondria. (iii) Mitochondrial substrate
      oxidation is coupled with the reduction of molecular oxygen, thus providing
      energy for cellular metabolism. Interestingly, recent in vivo studies have shown
      improved basal respiration and modulated mitochondrial oxidative phosphorylation
      by exogenous CH4. Overall, these data suggest that CH4 liberation and
      effectiveness in eukaryotes are both linked to hypoxic events and redox
      regulation and support the notion that CH4 has therapeutic roles in mammalian
      pathophysiologies.

PMID- 29181378
TI  - Screening of Dementia in Portuguese Primary Care: Methodology, Assessment Tools,
      and Main Results.
AB  - The objectives of this article are as follows: (1) to describe the assessment
      protocol used to outline people with probable dementia in Primary Health Care;
      (2) to show the methodological design and procedure to obtain a representative
      sample of patients with probable dementia; and (3) to report the main
      characteristics of the sample collected in the context of the study
      "Characteristics and needs of people with probable dementia." The study protocol
      was based on the "Community Assessment of Risk and Treatment Strategies (CARTS)
      Program" and is composed by a set of instruments that allow the assessment of
      older adults with probable dementia in several areas (health, psychological,
      functionality, and other). Descriptive analysis was used to characterize the
      final sample (n = 436). The study protocol as well as the methodological
      procedure to obtain the referral of research participants and data collection on
      the condition of people with probable dementia in Primary Health Care proved to
      be a valuable tool to obtain a sample of patients distributed by the full range
      of probable dementia in a large geographical area. Results may allocate the
      design of care pathways for old people with cognitive disorders to prevent, delay
      impairment, and/or optimize quality of life of patients.

PMID- 29181380
TI  - Production, Preservation, and Transfer of South American Camelid Embryos.
AB  - The current review summarizes progress in the field of in vitro and in vivo
      production of South American Camelid embryos. Both methods require ovarian
      superstimulation (with FSH and eCG) to obtain multiple ovulations (in vivo embryo
      production) or to induce follicle growth for oocyte collection (in vitro embryo
      production). Moreover, superstimulation entails prior administration of hormones
      that inhibit follicular growth (progesterone, progestagens, and estrogens).
      Cumulus-oocyte complexes obtained must mature in vivo (buserelin administration)
      or in vitro to then be subjected to in vitro fertilization or intracytoplasmic
      sperm injection. All these techniques also require morphologically normal, motile
      spermatozoa to achieve fertilization. Methods used to decrease semen viscosity
      and to select the best spermatozoa (Percoll(r); Androcoll-ETM) are described.
      Additionally, nuclear transfer or cloning has been applied in llamas. Up to now,
      embryo deep-freezing and vitrification have progressed slowly but are at the
      height of development. Embryos that are obtained by any of these techniques,
      either in vivo or in vitro, need to be transferred to synchronized recipient
      females. The best results are achieved after transfer to the left uterine horn
      with an ipsilateral ovulation. No live offspring have been obtained after the
      transfer of cryopreserved embryos. Applying reproductive biotechnologies, such as
      those described, will permit the expansion of genetically selected animals in the
      population and also that of wild camelid species, vicunas, and guanacos, whose
      embryos could then be transferred to the uterus of domestic species.

PMID- 29181379
TI  - Molecular Autopsy for Sudden Death in the Young: Is Data Aggregation the Key?
AB  - The Scripps molecular autopsy study seeks to incorporate genetic testing into the
      postmortem examination of cases of sudden death in the young (<45 years old).
      Here, we describe the results from the first 2 years of the study, which
      consisted of whole exome sequencing (WES) of a cohort of 50 cases predominantly
      from San Diego County. Apart from the individual description of cases, we
      analyzed the data at the cohort-level, which brought new perspectives on the
      genetic causes of sudden death. We investigated the advantages and disadvantages
      of using WES compared to a gene panel for cardiac disease (usually the first
      genetic test used by medical examiners). In an attempt to connect complex
      clinical phenotypes with genotypes, we classified samples by their genetic
      fingerprint. Finally, we studied the benefits of analyzing the mitochondrial DNA
      genome. In this regard, we found that half of the cases clinically diagnosed as
      sudden infant death syndrome had an increased ratio of heteroplasmic variants,
      and that the variants were also present in the mothers. We believe that community
      based data aggregation and sharing will eventually lead to an improved
      classification of variants. Allele frequencies for the all cases can be accessed
      via our genomics browser at https://genomics.scripps.edu/browser.

PMID- 29181381
TI  - Impact of Dietary Galacto-Oligosaccharide (GOS) on Chicken's Gut Microbiota,
      Mucosal Gene Expression, and Salmonella Colonization.
AB  - Preventing Salmonella colonization in young birds is key to reducing
      contamination of poultry products for human consumption (eggs and meat). While
      several Salmonella vaccines have been developed that are capable of yielding high
      systemic antibodies, it is not clear how effective these approaches are at
      controlling or preventing Salmonella colonization of the intestinal tract.
      Effective alternative control strategies are needed to help supplement the bird's
      ability to prevent Salmonella colonization, specifically by making the cecum less
      hospitable to Salmonella. In this study, we investigated the effect of the
      prebiotic galacto-oligosaccharide (GOS) on the cecal microbiome and ultimately
      the carriage of Salmonella. Day-old pullet chicks were fed control diets or diets
      supplemented with GOS (1% w/w) and then challenged with a cocktail of Salmonella
      Typhimurium and Salmonella Enteritidis. Changes in cecal tonsil gene expression,
      cecal microbiome, and levels of cecal and extraintestinal Salmonella were
      assessed at 1, 4, 7, 12, and 27 days post infection. While the Salmonella counts
      were generally lower in the GOS-treated birds, the differences were not
      significantly different at the end of the experiment. However, these data
      demonstrated that treatment with the prebiotic GOS can modify both cecal tonsil
      gene expression and the cecal microbiome, suggesting that this type of treatment
      may be useful as a tool for altering the carriage of Salmonella in poultry.

PMID- 29181382
TI  - Reinnervation of the diaphragm by the inferior laryngeal nerve to the phrenic
      nerve in ventilator-dependent tetraplegic patients with C3-5 damage.
AB  - The aim of this study was to evaluate the feasibility of unilateral diaphragmatic
      reinnervation in humans by the inferior laryngeal nerve. This pilot study
      included chronically ventilated tetraplegic patients with destruction of phrenic
      nerve motoneurons. Five patients were included. They all had a high level of
      tetraplegia, with phrenic nerve motor neuron destruction. They were highly
      dependent on ventilation, without any possibility of weaning. They did not have
      other chronic pathologies, especially laryngeal disease. They all had
      diaphragmatic explorations to diagnose the destruction of the motoneurons of the
      phrenic nerves and nasoendoscopy to be sure that they did not have laryngeal or
      pharyngeal disease. Then, surgical anastomosis of the right phrenic nerve was
      performed with the inferior laryngeal nerve, by a cervical approach. A laryngeal
      reinnervation was performed at the same time, using the ansa hypoglossi. One
      patient was excluded because of a functional phrenic nerve and one patient died 6
      months after the surgery of a cardiac arrest. The remaining three patients were
      evaluated after the anastomosis every 6 months. They did not present any
      swallowing or vocal alterations. In these three patients, the diaphragmatic
      explorations showed that there was a recovery of the diaphragmatic electromyogram
      of the right and left hemidiaphragms after 1 year. Two patients had surgical
      diaphragmatic explorations for diaphragmatic pacing 18-24 months after the
      reinnervation with excellent results. At 36 months, none of the patients could
      restore their automatic ventilation. In conclusion, this study demonstrated that
      diaphragmatic reinnervation by the inferior laryngeal nerve is effective, without
      any vocal or swallowing complications.

PMID- 29181383
TI  - High emergency organ allocation rule in lung transplantation: a simulation study.
AB  - The scarcity of suitable organ donors leads to protracted waiting times and
      mortality in patients awaiting lung transplantation. This study aims to assess
      the short- and long-term effects of a high emergency organ allocation policy on
      the outcome of lung transplantation. We developed a simulation model of lung
      transplantation waiting queues under two allocation strategies, based either on
      waiting time only or on additional criteria to prioritise the sickest patients.
      The model was informed by data from the United Network for Organ Sharing. We
      compared the impact of these strategies on waiting time, waiting list mortality
      and overall survival in various situations of organ scarcity. The impact of a
      high emergency allocation strategy depends largely on the organ supply. When
      organ supply is sufficient (>95 organs per 100 patients), it may prevent a small
      number of early deaths (1 year survival: 93.7% against 92.4% for waiting time
      only) without significant impact on waiting times or long-term survival. When the
      organ/recipient ratio is lower, the benefits in early mortality are larger but
      are counterbalanced by a dramatic increase of the size of the waiting list.
      Consequently, we observed a progressive increase of mortality on the waiting list
      (although still lower than with waiting time only), a deterioration of patients'
      condition at transplant and a decrease of post-transplant survival times. High
      emergency organ allocation is an effective strategy to reduce mortality on the
      waiting list, but causes a disruption of the list equilibrium that may have
      detrimental long-term effects in situations of significant organ scarcity.

PMID- 29181384
TI  - Identification and Characterization of the Diverse Stress-Responsive R2R3-RMYB
      Transcription Factor from Hibiscus sabdariffa L.
AB  - Various regulatory proteins play a fundamental role to manage the healthy plant
      growth under stress conditions. Differential display reverse transcriptase PCR
      and random amplification of cDNA ends (RACE) was used to explore the osmotic
      stress-responsive transcripts. We identified and characterized the salt stress
      responsive R2R3 type RMYB transcription factor from Hibiscus sabdariffa which has
      an open reading frame of 690 bp, encoding 229 long chain amino acids. In silico
      analysis confirmed the conserved R2 and R3 domain as well as an NLS-1
      localization site. The deduced amino acids of RMYB shared 83, 81, 80, 79, 72, 71,
      and 66% homology with Arabidopsis thaliana, Glycine max, Oryza sativa, Zea maize,
      Malus domestica, Populus tremula * Populus alba, and Medicago sativa specific MYB
      family, respectively. We observed the gene upregulation in stem, leaf, and root
      tissue in response to abiotic stress. Furthermore, RMYB gene was cloned into
      plant expression vector under CaMV35S promoter and transformed to Gossypium
      hirsutum: a local cotton cultivar. Overexpression of RMYB was observed in
      transgenic plants under abiotic stresses which further suggests its regulatory
      role in response to stressful conditions. The RMYB transcription factor
      overexpressing in transgenic cotton plants may be used as potential agent for the
      development of stress tolerant crop cultivars.

PMID- 29181385
TI  - Calcium Ionophore, Calcimycin, Kills Leishmania Promastigotes by Activating
      Parasite Nitric Oxide Synthase.
AB  - Leishmaniasis is an infectious disease caused by protozoan parasites of the genus
      Leishmania. There is no vaccine against human leishmaniasis and the treatment of
      the disease would benefit from a broader spectrum and a higher efficacy of
      leishmanicidal compounds. We analyzed the leishmanicidal activity and the
      mechanism of action of the calcium ionophore, calcimycin. L. major promastigotes
      were coincubated with calcimycin and the viability of the cells was assessed
      using resazurin assay. Calcimycin displayed dose-dependent effect with IC50 =
      0.16 MUM. Analysis of propidium iodide/LDS-751 stained promastigotes revealed
      that lower concentrations of calcimycin had cytostatic effect and higher
      concentrations had cytotoxic effect. To establish the mechanism of action of
      calcimycin, which is known to stimulate activity of mammalian constitutive nitric
      oxide synthase (NOS), we coincubated L. major promastigotes with calcimycin and
      selective NOS inhibitors ARL-17477 or L-NNA. Addition of these inhibitors
      substantially decreased the toxicity of calcimycin to Leishmania promastigotes.
      In doing so, we demonstrated for the first time that calcimycin has a direct
      leishmanicidal effect on L. major promastigotes. Also, we showed that Leishmania
      constitutive Ca2+/calmodulin-dependent nitric oxide synthase is involved in the
      parasite cell death. These data suggest activation of Leishmania nitric oxide
      synthase as a new therapeutic approach.

PMID- 29181386
TI  - The Influence of Different Oregano Species on the Antioxidant Activity Determined
      Using HPLC Postcolumn DPPH Method and Anticancer Activity of Carvacrol and
      Rosmarinic Acid.
AB  - The aim of this study was to evaluate concentration-dependent antioxidant and
      anticancer activities of CA and RA in ethanol extracts of three different Oregano
      species (Origanum onites L., Origanum vulgare L., and Origanum vulgare ssp.
      hirtum). The study revealed the highest RA antioxidant activity in O. vulgare
      ssp. hirtum (9550 +/- 95 mmol/g) and the lowest in O. vulgare L. (2605 +/- 52
      mmol/g) (p < 0.05). The highest CA amount was present in O. onites L., which was
      1.8 and 4.7 times higher (p < 0.05) than in O. vulgare ssp. hirtum and O. vulgare
      L., respectively. The anticancer activity was evaluated on human glioblastoma
      (U87) and triple-negative breast cancer (MDA-MB231) cell lines in vitro. RA
      anticancer activity was negligible. CA and the extracts were about 1.5-2 times
      more active against MDA-MB231 cell line (p < 0.05) compared to U87 cell line. The
      anticancer activities of three tested extracts were similar against U87 cell line
      (p > 0.05) but they had different activities against MDA-MB231 cell line.

PMID- 29181387
TI  - cAMP Response Element Binding Protein Expression in the Hippocampus of Rhesus
      Macaques with Chronic Ephedrine Addiction.
AB  - Background: Drug addiction is classified as a chronic relapse nature brain
      disease with complicated neurobiology mechanisms. There are an increasing number
      of researchers that are investigating the possible mechanisms for solving the
      thorny problem. Methods: The model of chronic addiction of rhesus monkey
      ephedrine was established, where changes in body weight and behavior were
      monitored. The expression of cAMP response element binding protein (CREB) in the
      hippocampus of rhesus monkeys was identified by real-time PCR and Western blot.
      Results: We were successful in establishing the chronic ephedrine addiction model
      in the rhesus macaques. They exhibited changes in body weight and behavior.
      Immunofluorescence showed that CREB was expressed in the nucleus of the
      hippocampus, and the expression of CREB mRNA and protein in the hippocampus were
      increased by real-time PCR and Western blot. The CREB positive expression in the
      hippocampus of the modeling group was significantly higher than in the control
      group. Conclusions: The changes of body weight and behavior of the rhesus monkeys
      after ephedrine chronic addiction were significant. The changes of CREB in the
      hippocampus of rhesus macaques with ephedrine chronic addiction are important
      molecular mechanisms, and the upregulation of CREB may be involved in the
      physiological pathology and behavior process in individuals with chronic
      ephedrine addiction.

PMID- 29181388
TI  - Early Production of the Neutrophil-Derived Lipid Mediators LTB4 and LXA4 Is
      Modulated by Intracellular Infection with Leishmania major.
AB  - Recruitment of neutrophil granulocytes to sites of infectious tissue damage is an
      early event in innate immune responses. Following chemotactic signals neutrophils
      establish a first line of defense in a swarm-like manner. Intracellular pathogens
      such as Leishmania major can, however, evade neutrophil-mediated killing and
      survive inside neutrophils. To achieve this the parasites evolved potent evasion
      mechanisms. Since neutrophils are a major source of inflammation regulating lipid
      mediators, we hypothesized that intracellular infection modifies the release of
      pro- and anti-inflammatory lipid mediators like leukotriene B4 (LTB4) and lipoxin
      A4 (LXA4), respectively. In the present study, we demonstrated in vitro that L.
      major-infected primary human neutrophils release an increased amount of LTB4,
      whereas LXA4 liberation is reduced during the first hours of infection. To
      investigate whether lipid mediator modulation is a common feature in
      intracellular infections, we tested the impact of an infection with Anaplasma
      phagocytophilum. Similarly to L. major, neutrophil infection with A.
      phagocytophilum led to an enhanced release of LTB4 and decreased LXA4 production.
      Together, our findings indicate that intracellular infections modulate the lipid
      mediator profile of neutrophils. This effect is likely to contribute to the
      survival of the pathogens in neutrophils and to the outcome of the infections.

PMID- 29181389
TI  - Cucurbitaceae Seed Protein Hydrolysates as a Potential Source of Bioactive
      Peptides with Functional Properties.
AB  - Seeds from Cucurbitaceae plants (squashes, pumpkins, melons, etc.) have been used
      both as protein-rich food ingredients and nutraceutical agents by many indigenous
      cultures for millennia. However, relatively little is known about the bioactive
      components (e.g., peptides) of the Cucurbitaceae seed proteins (CSP) and their
      specific effects on human health. Therefore, this paper aims to provide a
      comprehensive review of latest research on bioactive and functional properties of
      CSP isolates and hydrolysates. Enzymatic hydrolysis can introduce a series of
      changes to the CSP structure and improve its bioactive and functional properties,
      including the enhanced protein solubility over a wide range of pH values. Small
      sized peptides in CSP hydrolysates seem to enhance their bioactive properties but
      adversely affect their functional properties. Therefore, medium degrees of
      hydrolysis seem to benefit the overall improvement of bioactive and functional
      properties of CSP hydrolysates. Among the reported bioactive properties of CSP
      isolates and hydrolysates, their antioxidant, antihypertensive, and
      antihyperglycaemic activities stand out. Therefore, they could potentially
      substitute synthetic antioxidants and drugs which might have adverse secondary
      effects on human health. CSP isolates and hydrolysates could also be implemented
      as functional food ingredients, thanks to their favorable amino acid composition
      and good emulsifying and foaming properties.

PMID- 29181390
TI  - Gender Differences in the Progression of Experimental Chronic Kidney Disease
      Induced by Chronic Nitric Oxide Inhibition.
AB  - Chronic kidney disease (CKD) is considered a public health problem, assuming
      epidemic proportions worldwide. In this context, the preponderance of CKD
      prevalence in male over age-matched female patients is of note. In the present
      study, we investigated the impact of the gender on the development of
      experimental CKD induced by chronic nitric oxide (NO) inhibition in Wistar male
      and female rats through the administration of L-NAME. CKD model induced by L-NAME
      is characterized by systemic vasoconstriction, resulting in severe hypertension,
      albuminuria, renal ischemia, glomerulosclerosis, interstitial expansion, and
      macrophage infiltration. After 30 days of CKD induction, male NAME rats exhibited
      remarkable albuminuria, augmented cortical histological damage, interstitial
      inflammation, and fibrosis. Age-matched female NAME rats showed significantly
      lower albuminuria, diminished glomerular ischemia, and glomerulosclerosis, as
      well as a significant reduction in the expression of alpha-smooth muscle actin
      renal interstitial Ang II+ cells. Thus, the present study demonstrated that
      female rats submitted to the NAME model developed less severe CKD than males.
      Female renoprotection could be promoted by both the estrogen anti-inflammatory
      activity and/or by the lack of testosterone, related to renin-angiotensin
      aldosterone system hyperactivation and fibrogenesis. However, the influence of
      sex hormones on the progression of CKD needs to be further investigated.

PMID- 29181391
TI  - Barcoding the Dendrobium (Orchidaceae) Species and Analysis of the Intragenomic
      Variation Based on the Internal Transcribed Spacer 2.
AB  - Many species belonging to the genus Dendrobium are of great commercial value.
      However, their difficult growth conditions and high demand have caused many of
      these species to become endangered. Indeed, counterfeit Dendrobium products are
      common, especially in medicinal markets. This study aims to assess the
      suitability of the internal transcribed spacer 2 (ITS2) region as a marker for
      identifying Dendrobium and to evaluate its intragenomic variation in Dendrobium
      species. In total, 29,624 ITS2 copies from 18 species were obtained using 454
      pyrosequencing to evaluate intragenomic variation. In addition, 513 ITS2
      sequences from 26 Dendrobium species were used to assess its identification
      suitability. The highest intragenomic genetic distance was observed in Dendrobium
      chrysotoxum (0.081). The average intraspecific genetic distances of each species
      ranged from 0 to 0.032. Phylogenetic trees based on ITS2 sequences showed that
      most Dendrobium species are monophyletic. The intragenomic and intraspecies
      divergence analysis showed that greater intragenomic divergence is mostly
      correlated with larger intraspecific variation. As a major ITS2 variant becomes
      more common in genome, there are fewer intraspecific variable sites in ITS2
      sequences at the species level. The results demonstrated that the intragenomic
      multiple copies of ITS2 did not affect species identification.

PMID- 29181392
TI  - Long-Term Effectiveness of a Stress Management Intervention at Work: A 9-Year
      Follow-Up Study Based on a Randomized Wait-List Controlled Trial in Male
      Managers.
AB  - Objective: Short- and medium-term effectiveness (up to 3 years) of individual
      level stress management interventions (SMI) at work were demonstrated, yet long
      term effectiveness remains unexplored. We therefore aimed to address this
      research gap. Methods: 94 male middle managers participated in a randomized wait
      list controlled trial between 2006 and 2008 and in a post-trial-follow-up survey
      in 2015. During the first two years, all received an 18-hour psychotherapeutic
      SMI intervention which was based on the Effort-Reward Imbalance (ERI) model:
      tackling stressor on mismatch between effort and reward and promoting recovery on
      overcommitment. Work stress (i.e., ERI indicators) was the primary outcome, and
      the secondary outcome was depressive symptoms. The long-term effectiveness of the
      SMI was examined by mixed modeling, using an external control group (n = 94).
      Results: Effort and reward were substantially improved with significant
      intervention * time interaction effects (p < 0.001) compared to the external
      control group; effects on overcommitment and depressive symptoms were also
      significant (p < 0.05 and p < 0.01, resp.), though their trajectories in the
      intervention group were less sustainable. Conclusions: The effectiveness of this
      psychotherapeutic SMI at work based on the ERI model was observed over a 9-year
      period, particularly on the effort-reward ratio.

PMID- 29181393
TI  - Roles and Clinical Applications of Biomarkers in Cardiovascular Disease 2017.

PMID- 29181394
TI  - Corrigendum to "Serum Sclerostin Levels in Patients with Ankylosing Spondylitis
      and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis".
AB  - [This corrects the article DOI: 10.1155/2017/9295313.].

PMID- 29181396
TI  - Isometric Tunnel Placement in Ulnar Collateral Ligament Reconstruction with
      Single CT Scan.
AB  - Background: Isometric tunnel placement for anterior bundle of the medial
      collateral ligament (MCL) reconstruction is mandatory for successful surgery.
      Purpose: This study aimed to demonstrate a useful method for identifying
      isometric tunnel placement using a single computed tomography (CT) scan. Study
      Design: Descriptive Laboratory Study. Methods: Five normal elbows were scanned at
      4 different flexion angles at 45 degrees  increment. Three-dimensional models
      were analyzed using 2 different approaches: single and multiple CT scans methods.
      Ligament footprints in the humerus and the ulna were registered. Ligament length
      and isometric points were defined. The locations of the isometric points were
      imported into both methods to be compared. Results: There was no significant
      difference between 2 methods in calculating the length in every zone. There was
      also no significant difference in determining isometric ligament's origin point,
      which is located approximately 18.2 +/- 4.0 mm and 18.4 +/- 2.9 mm for single and
      multiple CT, respectively, measured inferolaterally from medial epicondyle.
      Conclusions: A solid preoperative plan is critical when predicting tunnel
      locations due to the difficulty in finding isometric points and the individuality
      of optimal bone tunnel locations. Using single CT scan, optimal locations can be
      predicted with the same accuracy as a multiple CT scans with less radiation
      exposure.

PMID- 29181397
TI  - Preoperative C-Reactive Protein as a Risk Factor for Postoperative Delirium in
      Elderly Patients Undergoing Laparoscopic Surgery for Colon Carcinoma.
AB  - Background: Postoperative delirium (POD) is a very common complication in
      operative disciplines, especially in those elderly patients after cardiac
      surgery. This study aimed to investigate the relationship between C-reactive
      protein (CRP) and POD in elderly patients undergoing laparoscopic surgery for
      colon carcinoma. Methods: 160 elderly patients scheduled to undergo selective
      laparoscopic surgery for colon carcinoma were prospectively recruited in this
      present study. The preoperative demographic and medical characteristics,
      intraoperative variables, and postoperative complications were all recorded in
      detail. POD assessment was performed once a day for the first 3 days and at 7th
      day after surgery, respectively. CRP concentrations preoperatively and on
      postoperative days 1, 2, and 3 were measured by using human enzyme linked
      immunosorbent assay (ELISA). Results: Of all the 160 enrolled patients, 39 had
      suffered POD with a POD incidence of 24.4% within the first week after the
      operation. The univariate analysis and multiple logistic regression analysis
      suggested preoperative CRP concentrations as the only independent predicator for
      POD in patients undergoing laparoscopic surgery for colon carcinoma (OR: 5.87;
      95% CI: 2.22-11.4; P = 0.018). Conclusions: This present study highlighted the
      predictive role of preoperative CRP concentrations for POD in elderly patients
      undergoing laparoscopic surgery for colon carcinoma.

PMID- 29181398
TI  - Rheumatoid Arthritis Affecting the Upper Cervical Spine: Biomechanical Assessment
      of the Stabilizing Ligaments.
AB  - Diameters of anterior and posterior atlantodental intervals (AADI and PADI) are
      diagnostically conclusive regarding ongoing neurological disorders in rheumatoid
      arthritis. MRI and X-ray are mostly used for patients' follow-up. This
      investigation aimed at analyzing these intervals during motion of cervical spine,
      when transverse and alar ligaments are damaged. AADI and PADI of 10 native, human
      cervical spines were measured using lateral fluoroscopy, while the spines were
      assessed in neutral position first, in maximal inclination second, and in maximal
      extension at last. First, specimens were evaluated under intact conditions,
      followed by analysis after transverse and alar ligaments were destroyed. Damage
      of the transverse ligament leads to an increase of the AADI's diameter about 0.65
      mm in flexion and damage of alar ligaments results in significant enhancement of
      3.59 mm at mean. In extension, the AADI rises 0.60 mm after the transverse
      ligament was cut and 0.90 mm when the alar ligaments are damaged. After all
      ligaments are destroyed, AADI assessed in extension closely resembles AADI at
      neutral position. Ligamentous damage showed an average significant decrease of
      the PADI of 1.37 mm in the first step and of 3.57 mm in the second step in
      flexion, while it is reduced about 1.61 mm and 0.41 mm in the extended and
      similarly in the neutrally positioned spine. Alar and transverse ligaments are
      both of obvious importance in order to prevent AAS and movement-related spinal
      cord compression. Functional imaging is necessary at follow-up in order to
      identify patients having an advanced risk of neurological disorders.

PMID- 29181395
TI  - Modulating Neuroinflammation to Treat Neuropsychiatric Disorders.
AB  - Neuroinflammation is recognised as one of the potential mechanisms mediating the
      onset of a broad range of psychiatric disorders and may contribute to
      nonresponsiveness to current therapies. Both preclinical and clinical studies
      have indicated that aberrant inflammatory responses can result in altered
      behavioral responses and cognitive deficits. In this review, we discuss the role
      of inflammation in the pathogenesis of neuropsychiatric disorders and ask the
      question if certain genetic copy-number variants (CNVs) associated with
      psychiatric disorders might play a role in modulating inflammation. Furthermore,
      we detail some of the potential treatment strategies for psychiatric disorders
      that may operate by altering inflammatory responses.

PMID- 29181399
TI  - MRI-Based Estimation of Scalar Cochlear-Implant Electrode Position.
AB  - The position of the cochlear-implant electrode is important to audiological
      outcomes after cochlear implantation. The common technique to evaluate the
      intracochlear electrode's position involves the use of ionized radiation in MSCT,
      DVT, or flat-panel tomography (FPT). Recent advances in knowledge regarding the
      handling of MRI artifacts in cochlear implantees indicate that estimating the
      intracochlear electrode's position with an MRI could be possible. This study's
      aim was to evaluate the ipsilaterally position of electrodes using MRI at 1.5 T.
      In a retrospective study of 10 implantees with postoperative need for MRI
      scanning, we evaluated the intrascalar electrode's position using a T2-weighted
      sequence at 1.5 T. We compared the resulting estimate of the intracochlear
      position with the estimates from the postoperative FPT scan and the
      intraoperative NRT ratio. For each ear, the MRI-estimated scalar position
      corresponded with the estimated positions from the FPT and NRT ratio. For eight
      ears, a scala tympani's position was observed in the MRI. In one case, an
      electrode scalar translocation was found. In one case, the scala vestibuli's
      position was observed. Thus, MRI-based estimation of the scalar position of a
      cochlear-implant electrode is possible. Limitations to this method include
      implant-specific magnet and fixation configurations, which can cause
      complications.

PMID- 29181400
TI  - Effects of Nitric Oxide on Renal Proximal Tubular Na+ Transport.
AB  - Nitric oxide (NO) has a wide variety of physiological functions in the kidney.
      Besides the regulatory effects in intrarenal haemodynamics and glomerular
      microcirculation, in vivo studies reported the diuretic and natriuretic effects
      of NO. However, opposite results showing the stimulatory effect of NO on Na+
      reabsorption in the proximal tubule led to an intense debate on its physiological
      roles. Animal studies have showed the biphasic effect of angiotensin II (Ang II)
      and the overall inhibitory effect of NO on the activity of proximal tubular Na+
      transporters, the apical Na+/H+ exchanger isoform 3, basolateral Na+/K+ ATPase,
      and the Na+/HCO3- cotransporter. However, whether these effects could be
      reproduced in humans remained unclear. Notably, our recent functional analysis of
      isolated proximal tubules demonstrated that Ang II dose-dependently stimulated
      human proximal tubular Na+ transport through the NO/guanosine 3',5'-cyclic
      monophosphate (cGMP) pathway, confirming the human-specific regulation of
      proximal tubular transport via NO and Ang II. Of particular importance for this
      newly identified pathway is its possibility of being a human-specific therapeutic
      target for hypertension. In this review, we focus on NO-mediated regulation of
      proximal tubular Na+ transport, with emphasis on the interaction with individual
      Na+ transporters and the crosstalk with Ang II signalling.

PMID- 29181401
TI  - Investigation into Hypoglycemic, Antihyperlipidemic, and Renoprotective
      Potentials of Dennettia tripetala (Pepper Fruit) Seed in a Rat Model of Diabetes.
AB  - This study investigated the hypoglycemic, antihyperlipidemic, and renoprotective
      potentials of Dennettia tripetala (DT) in a rat model of diabetes. The
      hypoglycemic activity in crude methanol seed extract of DT (CMEDT) and methanol
      seed fraction of DT (MFDT) measured by glucose oxidase method was increased by
      47.37% and 28.72%, respectively, after 8 hours of administration. After 10 days
      of treatment, CMEDT and MFDT gave a good glycemic control with the highest
      percentage reduction of 75.82% and 71.34% in glucose level, respectively, which
      is closely compared with 79.91% in glibenclamide. Using the enzymatic assay and
      Friedewald's equation, there was a significant reduction in serum level of total
      cholesterol (TC), triglyceride (TG), very-low-density lipoprotein (VLDL), and low
      density lipoprotein (LDL) and a significant increase in high-density lipoprotein
      (HDL) (p < 0.05) following treatment with CMEDT and MFDT, when compared with the
      untreated group, although results varied in dosed groups, with high dose of MFDT
      showing a better lipid-lowering activity. High dose of MFDT improved lipid
      metabolism and increased percentage protection against atherogenesis by 44%.
      However, neither CMEDT nor MFDT ameliorated the renal biochemical alteration in
      urea and creatinine. Thus, the study demonstrates hypoglycemic and
      antihyperlipidemic potentials of DT seed in diabetes.

PMID- 29181402
TI  - Effects of rhBMP-2 Loaded Titanium Reinforced Collagen Membranes on Horizontal
      Bone Augmentation in Dogs.
AB  - The aim of this study was to evaluate the efficacy of growth factor loaded
      collagen membranes on new bone formation during horizontal bone augmentation.
      Mandibular defects (4 * 4 * 4 mm) were surgically prepared in six male beagle
      dogs, which were then protected with one of three types of membranes: (1)
      titanium mesh, (2) titanium reinforced collagen, or (3) rhBMP-2 loaded titanium
      reinforced collagen. Animals were euthanized 8 and 16 weeks after surgery, and
      nondecalcified specimens were prepared and histomorphologically investigated to
      determine the degree of osteogenesis. Data were analyzed with Friedman test. With
      respect to the degree of osteogenesis at earlier stage (8 weeks after surgery),
      there was significantly higher new bone ratio in rhBMP-2 loaded membrane group (p
      > 0.05). However, with respect to the long-term results (16 weeks after surgery),
      there were no significant differences among the three membranes (p > 0.05). Based
      on histomorphometric analysis, there were no significant differences in
      horizontal bone gaining ratio (p > 0.05).

PMID- 29181403
TI  - GosB Inhibits Triacylglycerol Synthesis and Promotes Cell Survival in Mouse
      Mammary Epithelial Cells.
AB  - It has been demonstrated that the activator protein related transcription factor
      Finkel-Biskis-Jinkins murine osteosarcoma B (GosB) is involved in preadipocyte
      differentiation and triacylglycerol synthesis. However, the role of GosB in
      regulating the synthesis of milk fatty acid in mouse mammary glands remains
      unclear. This research uncovered potentially new roles of GosB in suppressing
      milk fatty acid synthesis. Results revealed that GosB had the highest expression
      in lung tissue and showed a higher expression level during nonlactation than
      during lactation. GosB inhibited the expression of fatty acid synthase (FASN),
      stearoyl-CoA desaturase (SCD), fatty acid binding protein 4 (FABP4),
      diacylglycerol acyltransferase 1 (DGAT1), perilipin 2 (PLIN2), perilipin 3
      (PLIN3), and C/EBPalpha in mouse mammary gland epithelial cells (MEC). In
      addition, GosB reduced cellular triglyceride content and the accumulation of
      lipid droplets; in particular, GosB enhanced saturated fatty acid concentration
      (C16:0 and C18:0). The PPARgamma agonist, rosiglitazone (ROSI), promoted
      apoptosis and inhibited cell proliferation. GosB increased the expression of Bcl
      2 and protected MEC from ROSI-induced apoptosis. Furthermore, MECs were protected
      from apoptosis through the GosB regulation of intracellular calcium
      concentrations. These findings suggest that GosB may regulate mammary epithelial
      cells milk fat synthesis and apoptosis via PPARgamma in mouse mammary glands.

PMID- 29181404
TI  - Delta9-Tetrahydrocannabinol Prevents Cardiovascular Dysfunction in STZ-Diabetic
      Wistar-Kyoto Rats.
AB  - The aim of this study was to determine if chronic, low-dose administration of a
      nonspecific cannabinoid receptor agonist could provide cardioprotective effects
      in a model of type I diabetes mellitus. Diabetes was induced in eight-week-old
      male Wistar-Kyoto rats via a single intravenous dose of streptozotocin (65 mg kg
      1). Following the induction of diabetes, Delta9-tetrahydrocannabinol was
      administered via intraperitoneal injection (0.15 mg kg-1 day-1) for an eight-week
      period until the animals reached sixteen weeks of age. Upon completion of the
      treatment regime, assessments of vascular reactivity and left ventricular
      function and electrophysiology were made, as were serum markers of oxidative
      stress and lipid peroxidation. Delta9-Tetrahydrocannabinol administration to
      diabetic animals significantly reduced blood glucose concentrations and
      attenuated pathological changes in serum markers of oxidative stress and lipid
      peroxidation. Positive changes to biochemical indices in diabetic animals
      conferred improvements in myocardial and vascular function. This study
      demonstrates that chronic, low-dose administration of Delta9-tetrahydrocannabinol
      can elicit antihyperglycaemic and antioxidant effects in diabetic animals,
      leading to improvements in end organ function of the cardiovascular system.
      Implications from this study suggest that cannabinoid receptors may be a
      potential new target for the treatment of diabetes-induced cardiovascular
      disease.

PMID- 29181406
TI  - Vertical-to-Horizontal Rotational Myocutaneous Flap for Repairing Cicatricial
      Lower Lid Ectropion: A Novel Surgical Technique.
AB  - Objective: To evaluate the efficacy and complications of a novel surgical
      technique for cicatricial lower lid ectropion that uses a vertical-to-horizontal
      (V-to-H) rotational myocutaneous flap procedure (Tsai procedure). Methods: We
      performed the V-to-H rotational myocutaneous flap procedure on 20 eyelids in 20
      patients with mild to moderate cicatricial lower lid ectropion. A vertical
      myocutaneous flap was created from the anterior lamella of the vertical pedicle
      in the lateral third of the lower eyelid. Following a horizontal relaxing
      incision from the base of the flap, a vertical myocutaneous flap was created and
      rotated to horizontal. Two patients with combined cicatricial ectropion and
      paralytic lagophthalmos simultaneously underwent additional lateral tarsorrhaphy.
      Results: After a minimum follow-up period of 6 months, all patients showed good
      anatomical and functional improvement with decreased dependence on topical
      lubricants and a satisfactory cosmetic appearance. Two patients with combined
      cicatricial and paralytic ectropion had mild residual asymptomatic lagophthalmos.
      No patients required further revision surgery and there were no complications or
      recurrence. Conclusion: The V-to-H rotational myocutaneous flap technique was an
      effective and simple one-stage procedure for correcting cicatricial lower lid
      ectropion. It lengthened the anterior lamella and tightened horizontal eyelid
      laxity without the need for a free skin graft.

PMID- 29181405
TI  - Review of Natural Product-Derived Compounds as Potent Antiglioblastoma Drugs.
AB  - Common care for glioblastoma multiforme (GBM) is a surgical resection followed by
      radiotherapy and temozolomide- (TMZ-) based chemotherapy. Unfortunately, these
      therapies remain inadequate involving severe mortality and recurrence. Recently,
      new approaches discovering combinations of multiple inhibitors have been proposed
      along with the identification of key driver mutations that are specific to each
      patient. To date, this approach is still limited by the lack of effective
      therapy. Hopefully, novel compounds derived from natural products are suggested
      as potential solutions. Inhibitory effects of natural products on angiogenesis
      and metastasis and cancer suppressive effect of altering miRNA expression are
      provident discoveries. Angelica sinensis accelerates apoptosis by their key
      substances influencing factors of apoptosis pathways. Brazilin displays antitumor
      features by making influence on reactive oxygen species (ROS) intensity.
      Sargassum serratifolium, flavonoids, and so on have antimetastasis effect. Ficus
      carica controls miRNA that inhibits translation of certain secretory pathway
      proteins during the UPR. Serratia marcescens and patupilone (EPO 906) are
      physically assessed materials through clinical trials related to GBM progression.
      Consequently, our review puts emphasis on the potential of natural products in
      GBM treatment by regulating multiple malignant cancer-related pathway solving
      pending problem such as reducing toxicity and side effect.

PMID- 29181407
TI  - Tomographic Evaluation of the Lower Incisor's Bone Limits in Mandibular Symphysis
      of Orthodontically Untreated Adults.
AB  - The amount of available bone in the lower incisor region is critical for
      periodontal preservation when planning large anteroposterior dental movements.
      The aims of this study were to evaluate bone limits of the lower incisors in the
      mandibular symphysis and to verify whether they are influenced by facial growth
      patterns, lower incisor inclinations, skeletal anteroposterior relationships, or
      patient age. Tomographic images of 40 orthodontically untreated patients were
      evaluated and measurements of width and height of the mandibular symphysis,
      thickness on the lingual and labial sides of the alveolar bone, and thickness of
      the entire alveolar bone were performed in sagittal view. The following
      cephalometric measurements were also evaluated: growth pattern (FHI), lower
      incisor inclination (IMPA), and skeletal anteroposterior relationships (AO-BO).
      Pearson's correlation test was used to assess associations among bone
      measurements, cephalometric measurements, and patients' ages. Weak to moderate
      positive correlations between FHI and bone measurements on the labial side of the
      incisors and total alveolar width were found. The height of the symphysis had a
      moderate negative correlation with FHI. It was concluded that patient age, FHI,
      and IMPA influenced bone limits of the lower incisors in the mandibular
      symphysis, while AO-BO had no influence.

PMID- 29181408
TI  - Body Posture Asymmetry in Prematurely Born Children at Six Years of Age.
AB  - Aims: The purpose of the study was to assess body posture asymmetries in the
      standing and sitting position in prematurely born children at six years of age.
      Study Design and Subjects: We measured trunk symmetry in coronal plane. The study
      was carried out in a group of 101 children, aged 6-7 years, mean age of 6.63,
      including 50 preterm children born at gestational age <32 weeks (preterm group)
      and 51 full-term children (control group). Outcome Measures: Trunk symmetry in
      coronal plane was measured using photogrammetric technique with Mora 4G CQ
      Elektronik. The subjects were examined in standing and sitting position.
      Statistical analyses were carried out using Shapiro-Wilk W-test, Student's t
      test, Mann-Whitney U test, and Pearson's chi-squared test. Statistical
      significance was assumed at p < 0.05. Results: No significant differences were
      found between the groups in the asymmetries identified in the relevant
      anthropometric points, relative to the position assumed during the examination or
      to the subjects' sex. Conclusions: There are no significant differences in body
      posture in the coronal plane, between preterm children and full-term children.
      Premature birth does not have adverse effects related to body posture asymmetry
      in preterm children at the age of six.

PMID- 29181409
TI  - Therapy Effects of Wogonin on Ovarian Cancer Cells.
AB  - Background: Wogonin is a plant monoflavonoid and has been reported to induce
      apoptosis of cancer cells and show inhibitory effect on cancer cell growth.
      However, the detailed and underlying molecular mechanisms are not elucidated. In
      this study, we investigated the molecular and biological effects of wogonin in
      human ovarian A2780 cancer cells. Materials and Methods: We determined the
      effects of wogonin on the changes of cell cycling and apoptotic responses of
      cells. Western blot analysis was used to measure the effects of wogonin on
      protein expressions. Results: Our results showed that treatment with wogonin
      inhibited the cancer cell proliferation, decreased the percentage of G0/G1
      subpopulation, and reduced invasiveness of A2780 cells. Exposure to wogonin also
      resulted in downregulated protein levels of estrogen receptor alpha (ER-alpha),
      VEGF, Bcl-2, and Akt and increased expressions of Bax and p53. In addition,
      exposure to wogonin increased caspase-3 cleavage and induced apoptosis in A2780
      cells. Our study further showed that MPP, a specific ER-alpha inhibitor,
      significantly enhanced antitumor effects of wogonin in A2780 cells. Conclusion:
      Our results suggest a potential clinical impact of wogonin on management of
      ovarian cancer.

PMID- 29181410
TI  - The Anti-Inflammatory Activity of Toonaciliatin K against Adjuvant Arthritis.
AB  - Toonaciliatin K is a natural limonoid purified from the Toona ciliata Roem. var.
      ciliata (Meliaceae). This study is to reveal the inflammatory suppression effect
      of toonaciliatin K and further the intrinsic mechanism. Firstly, anti
      inflammatory effect of toonaciliatin K was evaluated in lipopolysaccharide- (LPS
      ) induced RAW264.7 cells. RT-PCR results indicated that the mRNA expressions of
      TNF-alpha, IL-6, and IL-1beta were downregulated by toonaciliatin K. The
      toonaciliatin K inhibited TNF-alpha, IL-6, and IL-1beta levels stimulated by LPS.
      Furthermore, LPS elicited the excess iNOS and COX-2 mRNA and protein production
      and toonaciliatin K attenuated the excess production. Western blot assay
      demonstrated that MAPK and NF-kappaB signaling pathways play critical roles in
      the toonaciliatin K's anti-inflammatory activity. Secondly, toonaciliatin K
      inhibited carrageenan-induced paw edema in rats. Thirdly, toonaciliatin K
      alleviated the paw swelling and improved arthritis clinical scores in the
      adjuvant arthritis rats. Toonaciliatin K decreased the proinflammatory cytokines
      levels and Mankin scores in adjuvant arthritis rats. The HE staining, safranin O
      fast green, and toluidine blue staining results demonstrated that toonaciliatin K
      alleviated the histological changes of paw, for example, pannus formation, focal
      loss of cartilage, bone erosion, and presence of extra-articular inflammation.
      Hence, toonaciliatin K is a promising agent for treatment of arthritis.

PMID- 29181411
TI  - RNA-seq Based Transcription Characterization of Fusion Breakpoints as a Potential
      Estimator for Its Oncogenic Potential.
AB  - Based on high-throughput sequencing technology, the detection of gene fusions is
      no longer a big challenge but estimating the oncogenic potential of fusion genes
      remains challenging. Recent studies successfully applied machine learning methods
      and gene structural and functional features of fusion mutation to predict their
      oncogenic potentials. However, the transcription characterizations features of
      fusion genes have not yet been studied. In this study, based on the clonal
      evolution theory, we hypothesized that a fusion gene is more likely to be an
      oncogenic genomic alteration, if the neoplastic cells harboring this fusion
      mutation have larger clonal size than other neoplastic cells in a tumor. We
      proposed a novel method, called iFCR (internal Fusion Clone Ratio), given an
      estimation of oncogenic potential for fusion mutations. We have evaluated the
      iFCR method in three public cancer transcriptome sequencing datasets; the results
      demonstrated that the fusion mutations occurring in tumor samples have higher
      internal fusion clone ratio than normal samples. And the most frequent prostate
      cancer fusion mutation, TMPRSS2-ERG, appears to have a remarkably higher iFCR
      value in all three independent patients. The preliminary results suggest that the
      internal fusion clone ratio might potentially advantage current fusion mutation
      oncogenic potential prediction methods.

PMID- 29181413
TI  - Comment on "Prevalence and Risk Factors for Diabetic Lower Limb Amputation: A
      Clinic-Based Case Control Study".

PMID- 29181414
TI  - High Fasting Plasma Glucose during Early Pregnancy: A Review about Early
      Gestational Diabetes Mellitus.
AB  - Fasting plasma glucose (FPG) is nowadays routinely measured during early
      pregnancy to detect preexisting diabetes (FPG >= 7 mmol/L). This screening has
      concomitantly led to identify early intermediate hyperglycemia, defined as FPG in
      the 5.1 to 6.9 mmol/L range, also early gestational diabetes mellitus (eGDM).
      Early FPG has been associated with poor pregnancy outcomes, but the
      recommendation by the IADPSG to refer women with eGDM for immediate management is
      more pragmatic than evidence based. Although eGDM is characterized by insulin
      resistance and associated with classical risk factors for type 2 diabetes and
      incident diabetes after delivery, it is not necessarily associated with
      preexisting prediabetes. FPG >= 5.1 mmol/L in early pregnancy is actually poorly
      predictive of gestational diabetes mellitus diagnosed after 24 weeks of
      gestation. An alternative threshold should be determined but may vary according
      to ethnicity, gestational age, and body mass index. Finally, observational data
      suggest that early management of intermediate hyperglycemia may improve
      prognosis, through reduced gestational weight gain and potential early
      introduction of hypoglycemic agents. Considering all these issues, we suggest an
      algorithm for the management of eGDM based on early FPG levels that would be
      measured in case of risk factors. Nevertheless, interventional randomized trials
      are still missing.

PMID- 29181412
TI  - Antioxidative Effects of Natural Products on Diabetic Cardiomyopathy.
AB  - Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes and
      results in high mortality. It is therefore imperative to develop novel
      therapeutics for the prevention or inhibition of the progression of DCM.
      Oxidative stress is a key mechanism by which diabetes induces DCM. Hence,
      targeting of oxidative stress-related processes in DCM could be a promising
      therapeutic strategy. To date, a number of studies have shown beneficial effects
      of several natural products on the attenuation of DCM via an antioxidative
      mechanism of action. The aim of the present review is to provide a comprehensive
      and concise overview of the previously reported antioxidant natural products in
      the inhibition of DCM progression. Clinical trials of the antioxidative natural
      products in the management of DCM are included. In addition, discussion and
      perspectives are further provided in the present review.

PMID- 29181415
TI  - Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion
      Model of Acute Kidney Injury.
AB  - STAT3 is a transcriptional regulator that plays an important role in coordinating
      inflammation and immunity. In addition, there is a growing appreciation of the
      role STAT3 signaling plays in response to organ injury following diverse insults.
      Acute kidney injury (AKI) from ischemia-reperfusion injury is a common clinical
      entity with devastating consequences, and the recognition that endothelial
      alterations contribute to kidney dysfunction in this setting is of growing
      interest. Consequently, we used a mouse with a genetic deletion of Stat3
      restricted to the endothelium to examine the role of STAT3 signaling in the
      pathophysiology of ischemic AKI. In a mouse model of ischemic AKI, the loss of
      endothelial STAT3 signaling significantly exacerbated kidney dysfunction,
      morphologic injury, and proximal tubular oxidative stress. The increased severity
      of ischemic AKI was associated with more robust endothelial-leukocyte adhesion
      and increased tissue accumulation of F4/80+ macrophages. Moreover, important
      proximal tubular adaptive mechanisms to injury were diminished in association
      with decreased tissue mRNA levels of the epithelial cell survival cytokine IL-22.
      In aggregate, these findings suggest that the endothelial STAT3 signaling plays
      an important role in limiting kidney dysfunction in ischemic AKI and that
      selective pharmacologic activation of endothelial STAT3 signaling could serve as
      a potential therapeutic target.

PMID- 29181416
TI  - CD80 Expressed by CD8+ T Cells Contributes to PD-L1-Induced Apoptosis of
      Activated CD8+ T Cells.
AB  - Tumor cells are capable of limiting antitumor CD8+ T cell responses through their
      cell surface expression of PD-L1. In addition to PD-1 expressed by CD8+ T cells,
      PD-L1 also binds to CD80 expressed by CD8+ T cells. The influence of the PD
      L1/CD80 interaction on CD8+ T cell function has not been fully characterized, so
      we sought to investigate the impact of the PD-L1/CD80 interaction on PD-L1
      induced apoptosis of activated CD8+ T cells. We found that CD8+ T cells that
      lacked CD80 expression got activated to the same extent as wild-type CD8+ T
      cells, but when cultured with anti-CD3 and PD-L1/Fc protein, activated CD8+ T
      cells that lacked CD80 expression survived better than activated wild-type CD8+ T
      cells. These findings indicate that PD-L1 induces apoptosis in activated CD8+ T
      cells in part by signaling through CD80. Thus, in the design and implementation
      of checkpoint blockade therapies that target PD-L1, it is essential that both
      binding partners for PD-L1, PD-1, and CD80 are considered.

PMID- 29181417
TI  - Toll-Like Receptor Ligand-Induced Liver Injury in D-Galactosamine-Sensitized
      Mice: Differences between TLR7/8 and TLR9 Ligands, Cytokine Patterns, and Cross
      Tolerance Induction by TLR2 Ligand Pretreatment.
AB  - Administration of Toll-like receptor ligands (TLRLs) is known to cause liver
      injury in D-galN-sensitized mice. In the present study, we aimed to complement
      preceding reports on the TLRL/D-galN system by analyzing comparisons among TLRLs,
      mouse strain dependence, effects on serum levels of cytokines, and effects of
      sequential administrations of different TLRLs. In a preliminary set of analyses,
      we first confirmed that liver failure can be induced by diverse TLRLs, including
      LTA and R848 in combination with D-galN. Analysis using TLR4-deficient mice
      excluded potential confounding effects of endogenous TLR4Ls that include those
      referred to as DAMPs in CpG DNA/D-galN hepatotoxicity. Subsequently, we showed
      that LTA pretreatment could prevent mortality in both CpG DNA/D-galN- and R848/D
      galN-treated mice compared to without pretreatment. Incidentally, we observed
      that without the LTA pretreatment, CpG DNA/D-galN showed relatively higher liver
      specific toxicity whereas R848/D-galN showed more symptoms of multiple organ
      failure. These findings suggest that, in D-galN-sensitized mice, different TLRLs
      not only show similarity in the ability to induce hepatic injury but also exhibit
      distinctive abilities in inducing systemic inflammation and multiple organ
      failure. These findings also suggest the potential usefulness of cross-tolerance
      induction using LTA in the prevention of organ failure in TLRL-mediated acute
      inflammation.

PMID- 29181418
TI  - Asymptomatic Cardiovascular Syphilis With Aortic Regurgitation Requiring Surgical
      Repair in an HIV-Infected Patient.
AB  - A 47-year-old man with HIV infection presented 10 years after initial secondary
      syphilis diagnosis and treatment for routine follow-up. His HIV was well
      controlled on antiretroviral therapy. Rapid plasma reagin was 1:1, and TP-PA was
      reactive. Physical examination revealed a wide pulse pressure, a systolic murmur,
      and an early diastolic decrescendo murmur. Echocardiogram revealed moderate to
      severe aortic regurgitation, and subsequent computed tomography angiogram showed
      a 6.8-cm fusiform aneurysm of the proximal ascending aorta. Aortic valve and
      ascending hemiarch replacement were performed. Pathology showed adventitial
      inflammation with plasma cells, gumma-like amorphous areas surrounded by
      histiocytes, and giant cells with calcified plaques. Cardiovascular syphilis,
      while rare, remains a relevant cause of aortic aneurysm, even in previously
      treated patients. The physical exam can be critical in identifying this
      potentially fatal complication.

PMID- 29181419
TI  - Decrease in Seminal HIV-1 RNA Load After Praziquantel Treatment of Urogenital
      Schistosomiasis Coinfection in HIV-Positive Men-An Observational Study.
AB  - Background: Urogenital schistosomiasis due to Schistosoma hematobium infection is
      hypothesized to cause increased HIV-1 RNA shedding in semen in HIV co-infected
      men as result of chronic egg-induced inflammation in the prostate and the seminal
      vesicles. The effect of treatment with the antihelminthic agent praziquantel on
      seminal HIV-1 RNA load was assessed in this study. Methods: HIV-1 RNA load was
      determined in blood plasma and semen at baseline and at 10-week follow-up.
      Praziquantel was administered at baseline and two weeks later. Results: Eighteen
      HIV-positive men with S. haematobium co-infection were enrolled into the study.
      Status of antiretroviral therapy (ART): 6 ART-naive and 12 ART-experienced. All
      participants became egg-negative in urine at follow-up. Among the ART-naive men,
      the mean HIV-1 RNA load decreased by 0.32 log10 copies per mL (4.41 vs 4.09) in
      blood plasma from baseline to follow-up, and in semen by 1.06 log10 copies per mL
      (4.06 vs 3.00). Conclusions: This study demonstrated a decline in seminal HIV-1
      RNA load following praziquantel treatment of urogenital schistosomiasis infection
      in HIV-positive men. The finding needs further exploration in a larger randomized
      study targeting praziquantel as a supplementary preventive measure of sexual
      transmission of HIV-1 in S. haematobium endemic areas in sub-Saharan Africa.

PMID- 29181420
TI  - Autoantibodies to Granulocyte-Macrophage Colony-Stimulating Factor Associated
      With Severe and Unusual Manifestations of Cryptococcus gattii Infections.
AB  - Cryptococcus gattii infections, especially including those with severe clinical
      manifestations, may be related to underlying host immunologic factors. We present
      2 cases with autoantibodies to granulocyte-macrophage colony-stimulating factor
      (GM-CSF), a key cytokine in macrophage function. Immunologic evaluation for anti
      GM-CSF antibodies may be important to inform management and counseling.

PMID- 29181421
TI  - Sociodemographic and Clinical Factors Associated With Increasing Bacterial
      Sexually Transmitted Infection Diagnoses in Men Who Have Sex With Men Accessing
      Care at a Boston Community Health Center (2005-2015).
AB  - Background: The reasons why bacterial sexually transmitted infections (BSTIs) are
      increasing in US men who have sex with men (MSM) have not been fully
      characterized. Methods: An open cohort of MSM accessing medical care at a Boston
      community health center was used to assess secular trends in BSTI diagnoses.
      Frequency of infection and the estimated population size were used to calculate
      diagnosis rates. Poisson models were fit for multivariable analyses. Results:
      Between 2005 and 2015, 19 232 men had at least 1 clinic visit. Most (72.4%) were
      white; 6.0% were black, and 6.1% were Latino. Almost half had documented self
      report of identifying as gay (42.6%) or bisexual (3.2%). Most had private health
      insurance (61.7%); 5.4% had Medicare, 4.6% had Medicaid, and 8.4% reported no
      insurance. Between 2005 and 2015, BSTI diagnoses increased more than 8-fold. In
      2015, of 1319 men who were diagnosed with at least 1 BSTI; 291 were diagnosed
      with syphilis, 554 with gonorrhea (51.4% rectal, 31.0% urogenital), and 679 with
      chlamydia (69.1% rectal, 34.3% urogenital). In 2015, 22.7% of BSTIs were
      diagnosed among HIV-infected patients (15.4% of the clinic population), and 32.8%
      of BSTIs were diagnosed among HIV-uninfected patients using pre-exposure
      prophylaxis (PrEP; 10.1% of all men in care). In multivariable analyses, age 18
      to 24 years, being HIV-infected, using PrEP, being nonwhite, or reporting
      Medicaid or not reporting having private insurance or Medicare were independently
      associated with being diagnosed with a new BSTI. Conclusions: Over the past
      decade, BSTI diagnosis rates increased in HIV-infected and uninfected MSM, with
      disproportionate increases in PrEP users, racial and ethnic minority MSM, those
      aged 25 to 34 years, and those without stable health insurance, warranting
      focused education, screening, and accessible services for these key
      subpopulations.

PMID- 29181423
TI  - Biliary Strongyloides stercoralis With Cholecystitis and Extensive Portal Vein
      Thrombosis.
AB  - We report the rare finding of Strongyloides stercoralis rhabditiform larvae in
      biliary fluid, here associated with cholecystitis and near total portal vein
      thrombosis. The role of S. stercoralis leading to atypical clinical presentations
      and difficulty diagnosing strongyloidiasis in such patients with appropriate
      geographic exposure is discussed.

PMID- 29181422
TI  - Carbapenem-Resistant Enterobacteriaceae Infections in Patients on Renal
      Replacement Therapy.
AB  - Background: Patients on chronic intermittent renal replacement therapy (RRT) are
      at risk for infection with carbapenem-resistant Enterobacteriaceae (CRE).
      However, the impact of RRT on outcomes after CRE infections remains to be
      defined. Here we perform a comparison of outcomes for CRE-infected patients with
      preserved renal function compared with CRE-infected patients on RRT. Methods:
      Cases and controls were defined from a prospective cohort of CRE-infected
      patients from the Consortium on Resistance against Carbapenems in Klebsiella and
      other Enterobacteriaceae (CRACKLE). Cases were defined as CRE-infected patients
      on RRT at hospital admission, while controls were defined as CRE-infected
      patients with serum creatinine <2 mg/dL and not receiving RRT at admission. Risk
      factors for 28-day in-hospital mortality were assessed using multivariable
      logistic regression. An ordinal ranking of outcomes by desirability analysis was
      performed. Results: Patients on RRT were more likely to have diabetes mellitus
      and cardiac disease than controls. Urinary sources of infection were less common
      in the RRT group. In RRT patients, 28-day in-hospital mortality was increased as
      compared with controls: 22/71 (31%) vs 33/295 (11%). RRT remained significantly
      associated with 28-day in-hospital mortality after adjustment for source of
      infection, prehospitalization origin, and severity of illness (adjusted odds
      ratio, 2.27; 95% confidence interval [CI], 1.09-4.68; P = .03). Using univariable
      desirability of outcome ranking analysis, RRT status was associated with a 68%
      (95% CI, 61%-74%) chance of a worse disposition outcome. Conclusions: Chronic RRT
      in CRE-infected patients is associated with increased in-hospital mortality and
      worse disposition outcomes at 28 days.

PMID- 29181424
TI  - Comparative Effectiveness of Prophylactic Strategies for Perinatal Transmission
      of Hepatitis B Virus: A Network Meta-analysis of Randomized Controlled Trials.
AB  - Background: Perinatal transmission is the main route of hepatitis B virus (HBV)
      transmission. While several measures have been attempted as means of preventing
      perinatal HBV transmission, the optimal strategy remains inconclusive. Methods:
      We conducted a comprehensive search, through December 2016, for randomized
      controlled trials (RCTs) that compared the following measures among pregnant
      women with HBV infection: placebo/none, active immunoprophylaxis (hepatitis B
      vaccine series starting at birth [HBVac]), passive-active immunoprophylaxis
      (hepatitis B immunoglobulin and vaccine [HBIG+HBVac]), prenatal HBIG
      administration (HBIG/HBIG+HBVac), and prenatal antiviral therapy
      (AVT/HBIG+HBVac). Direct, indirect, and network meta-analyses were performed for
      all treatment comparisons. Results: Fifteen RCTs involving 2706 infants of HBV
      carrier mothers were eligible for analysis. Network meta-analysis demonstrated
      similar results as direct and indirect comparisons. HBVac alone significantly
      reduced the risk of hepatitis B infection in infants of HBV carrier mothers
      (relative risk [RR], 0.32; 95% confidence interval [CI], 0.21-0.50). The
      combination of immunoglobulin with vaccine is superior to vaccine alone (RR,
      0.37; 95% CI, 0.20-0.67). Prenatal HBIG administration and antiviral therapy
      offer further advantages over current passive-active immunoprophylaxis for
      infants of highly viremic (HBV DNA level higher than 2 * 105 IU/mL) mothers (RR,
      0.47; 95% CI, 0.29-0.75; and RR, 0.31; 95% CI, 0.10-0.99, respectively). There
      was no significant publication bias. Conclusions: Based on the universal
      infantile vaccination program, HBIG for infants born to HBV carrier mothers
      further reduces transmission. For highly viremic mothers whose children are still
      at risk for transmission under current immunoprophylaxis, prenatal HBIG
      administration or antiviral therapy in late pregnancy may be considered if more
      long-term evidence supports its efficacy and safety.

PMID- 29181425
TI  - Label-free photoacoustic tomography of whole mouse brain structures ex vivo.
AB  - Capitalizing on endogenous hemoglobin contrast, photoacoustic-computed tomography
      (PACT), a deep-tissue high-resolution imaging modality, has drawn increasing
      interest in neuroimaging. However, most existing studies are limited to
      functional imaging on the cortical surface and the deep brain structural imaging
      capability of PACT has never been demonstrated. Here, we explicitly studied the
      limiting factors of deep brain PACT imaging. We found that the skull distorted
      the acoustic signal and blood suppressed the structural contrast from other
      chromophores. When the two effects are mitigated, PACT can potentially provide
      high-resolution label-free imaging of structures in the entire mouse brain. With
      [Formula: see text] in-plane resolution, we can clearly identify major structures
      of the brain, which complements magnetic resonance microscopy for imaging small
      animal brain structures. Spectral PACT studies indicate that structural contrasts
      mainly originate from cytochrome distribution and that the presence of lipid
      sharpens the image contrast; brain histology results provide further validation.
      The feasibility of imaging the structure of the brain in vivo is also discussed.
      Our results demonstrate that PACT is a promising modality for both structural and
      functional brain imaging.

PMID- 29181426
TI  - Mitochondrial matrix pH as a decisive factor in neurometabolic imaging.
AB  - Alterations of cellular bioenergetics are a common feature in most
      neurodegenerative disorders. However, there is a selective vulnerability of
      different brain regions, cell types, and even mitochondrial populations to these
      metabolic disturbances. Thus, the aim of our study was to establish and validate
      an in vivo metabolic imaging technique to screen for mitochondrial function on
      the subcellular level. Based on nicotinamide adenine dinucleotide (phosphate)
      fluorescence lifetime imaging microscopy [NAD(P)H FLIM], we performed a
      quantitative correlation to high-resolution respirometry. Thereby, we revealed
      mitochondrial matrix pH as a decisive factor in imaging NAD(P)H redox state. By
      combining both parameters, we illustrate a quantitative, high-resolution
      assessment of mitochondrial function in metabolically modified cells as well as
      in an amyloid precursor protein-overexpressing model of Alzheimer's disease. Our
      metabolic imaging technique provides the basis for dissecting mitochondrial
      deficits not only in a range of neurodegenerative diseases, shedding light onto
      bioenergetic failures of cells remaining in their metabolic microenvironment.

PMID- 29181428
TI  - Pulmonary nodule classification in lung cancer screening with three-dimensional
      convolutional neural networks.
AB  - A three-dimensional (3-D) convolutional neural network (CNN) trained from scratch
      is presented for the classification of pulmonary nodule malignancy from low-dose
      chest CT scans. Recent approval of lung cancer screening in the United States
      provides motivation for determining the likelihood of malignancy of pulmonary
      nodules from the initial CT scan finding to minimize the number of follow-up
      actions. Classifier ensembles of different combinations of the 3-D CNN and
      traditional machine learning models based on handcrafted 3-D image features are
      also explored. The dataset consisting of 326 nodules is constructed with balanced
      size and class distribution with the malignancy status pathologically confirmed.
      The results show that both the 3-D CNN single model and the ensemble models with
      3-D CNN outperform the respective counterparts constructed using only traditional
      models. Moreover, complementary information can be learned by the 3-D CNN and the
      conventional models, which together are combined to construct an ensemble model
      with statistically superior performance compared with the single traditional
      model. The performance of the 3-D CNN model demonstrates the potential for
      improving the lung cancer screening follow-up protocol, which currently mainly
      depends on the nodule size.

PMID- 29181427
TI  - Effect of short-term colored-light exposure on cerebral hemodynamics and
      oxygenation, and systemic physiological activity.
AB  - There is not yet a comprehensive view of how the color of light affects the
      cerebral and systemic physiology in humans. The aim was to address this deficit
      through basic research. Since cerebral and systemic physiological parameters are
      likely to interact, it was necessary to establish an approach, which we have
      termed "systemic-physiology-augmented functional near-infrared spectroscopy (SPA
      fNIRS) neuroimaging." This multimodal approach measures the systemic and cerebral
      physiological response to exposure to light of different colors. In 14 healthy
      subjects (9 men, 5 women, age: [Formula: see text] years, range: 24 to 57 years)
      exposed to red, green, and blue light (10-min intermittent wide-field visual
      color stimulation; [Formula: see text] blocks of visual stimulation), brain
      hemodynamics and oxygenation were measured by fNIRS on the prefrontal cortex
      (PFC) and visual cortex (VC) simultaneously, in addition with systemic
      parameters. This study demonstrated that (i) all colors elicited responses in the
      VC, whereas only blue evoked a response in the PFC; (ii) there was a color
      dependent effect on cardiorespiratory activity; (iii) there was significant
      change in neurosystemic functional connectivity; (iv) cerebral hemodynamic
      responses in the PFC and changes in the cardiovascular system were gender and age
      dependent; and (v) electrodermal activity and psychological state showed no
      stimulus-evoked changes, and there was no dependence on color of light, age, and
      gender. We showed that short-term light exposure caused color-dependent responses
      in cerebral hemodynamics/oxygenation as well as cardiorespiratory dynamics.
      Additionally, we showed that neurosystemic functional connectivity changes even
      during apparently stress-free tasks-an important consideration when using any of
      the hemodynamic neuroimaging methods (e.g. functional magnetic resonance imaging,
      positron emission tomography, and fNIRS). Our findings are important for future
      basic research and clinical applications as well as being relevant for everyday
      life.

PMID- 29181429
TI  - Lung nodule volume quantification and shape differentiation with an ultra-high
      resolution technique on a photon-counting detector computed tomography system.
AB  - An ultra-high resolution (UHR) mode, with a detector pixel size of [Formula: see
      text] relative to isocenter, has been implemented on a whole body research photon
      counting detector (PCD) computed tomography (CT) system. Twenty synthetic lung
      nodules were scanned using UHR and conventional resolution (macro) modes and
      reconstructed with medium and very sharp kernels. Linear regression was used to
      compare measured nodule volumes from CT images to reference volumes. The full
      width-at-half-maximum of the calculated curvature histogram for each nodule was
      used as a shape index, and receiver operating characteristic analysis was
      performed to differentiate sphere- and star-shaped nodules. Results showed a
      strong linear relationship between measured nodule volumes and reference volumes
      for both modes. The overall volume estimation was more accurate using UHR mode
      and the very sharp kernel, having 4.8% error compared with 10.5% to 12.6% error
      in the macro mode. The improvement in volume measurements using the UHR mode was
      more evident for small nodule sizes or star-shaped nodules. Images from the UHR
      mode with the very sharp kernel consistently demonstrated the best performance
      [[Formula: see text]] for separating star- from sphere-shaped nodules, showing
      advantages of UHR mode on a PCD CT scanner for lung nodule characterization.

PMID- 29181430
TI  - Automatic selection of landmarks in T1-weighted head MRI with regression forests
      for image registration initialization.
AB  - Medical image registration establishes a correspondence between images of
      biological structures, and it is at the core of many applications. Commonly used
      deformable image registration methods depend on a good preregistration
      initialization. We develop a learning-based method to automatically find a set of
      robust landmarks in three-dimensional MR image volumes of the head. These
      landmarks are then used to compute a thin plate spline-based initialization
      transformation. The process involves two steps: (1) identifying a set of
      landmarks that can be reliably localized in the images and (2) selecting among
      them the subset that leads to a good initial transformation. To validate our
      method, we use it to initialize five well-established deformable registration
      algorithms that are subsequently used to register an atlas to MR images of the
      head. We compare our proposed initialization method with a standard approach that
      involves estimating an affine transformation with an intensity-based approach. We
      show that for all five registration algorithms the final registration results are
      statistically better when they are initialized with the method that we propose
      than when a standard approach is used. The technique that we propose is generic
      and could be used to initialize nonrigid registration algorithms for other
      applications.

PMID- 29181431
TI  - Neovascularization detection in diabetic retinopathy from fluorescein angiograms.
AB  - Although a lot of work has been done on optical coherence tomography and color
      images in order to detect and quantify diseases such as diabetic retinopathy,
      exudates, or neovascularizations, none of them is able to evaluate the diffusion
      of the neovascularizations in retinas. Our work has been to develop a tool that
      is able to quantify a neovascularization and the fluorescein leakage during an
      angiography. The proposed method has been developed following a clinical trial
      protocol; images are taken by a Spectralis (Heidelberg Engineering). Detections
      are done using a supervised classification using specific features. Images and
      their detected neovascularizations are then spatially matched by an image
      registration. We compute the expansion speed of the liquid that we call diffusion
      index. This last one specifies the state of the disease, permits indication of
      the activity of neovascularizations, and allows a follow-up of patients. The
      method proposed in this paper has been built to be robust, even with laser
      impacts, to compute a diffusion index.

PMID- 29181432
TI  - Cochlear implant phantom for evaluating computed tomography acquisition
      parameters.
AB  - Cochlear implants (CIs) are surgically implantable neuroprosthetic devices used
      to treat profound hearing loss. Recent literature indicates that there is a
      correlation between the final intracochlear positioning of the CI electrode
      arrays and the ultimate hearing outcome of the patient, indicating that further
      studies to better understand the relationship between electrode position and
      outcomes could have significant implications for future surgical techniques,
      array design, and processor programming methods. Postimplantation high-resolution
      computed tomography (CT) imaging is the best modality for localizing electrodes
      and provides the resolution necessary to visually identify electrode position,
      although with an unknown degree of accuracy depending on image acquisition
      parameters, like the hounsfield unit (HU) range of reconstruction, orientation,
      radiation dose, and image resolution. We report on the development of a phantom
      and on its use to study how four acquisition parameters, including image
      resolution and HU range of reconstruction, affect how accurately the true
      position of the electrodes can be found in a dataset of CT scans acquired from
      multiple helical and cone beam scanners. We also show how the phantom can be used
      to evaluate the effect of acquisition parameters on automatic electrode
      localization techniques.

PMID- 29181433
TI  - Tumor image signatures and habitats: a processing pipeline of multimodality
      metabolic and physiological images.
AB  - To create tumor "habitats" from the "signatures" discovered from multimodality
      metabolic and physiological images, we developed a framework of a processing
      pipeline. The processing pipeline consists of six major steps: (1) creating
      superpixels as a spatial unit in a tumor volume; (2) forming a data matrix
      [Formula: see text] containing all multimodality image parameters at superpixels;
      (3) forming and clustering a covariance or correlation matrix [Formula: see text]
      of the image parameters to discover major image "signatures;" (4) clustering the
      superpixels and organizing the parameter order of the [Formula: see text] matrix
      according to the one found in step 3; (5) creating "habitats" in the image space
      from the superpixels associated with the "signatures;" and (6) pooling and
      clustering a matrix consisting of correlation coefficients of each pair of image
      parameters from all patients to discover subgroup patterns of the tumors. The
      pipeline was applied to a dataset of multimodality images in glioblastoma (GBM)
      first, which consisted of 10 image parameters. Three major image "signatures"
      were identified. The three major "habitats" plus their overlaps were created. To
      test generalizability of the processing pipeline, a second image dataset from
      GBM, acquired on the scanners different from the first one, was processed. Also,
      to demonstrate the clinical association of image-defined "signatures" and
      "habitats," the patterns of recurrence of the patients were analyzed together
      with image parameters acquired prechemoradiation therapy. An association of the
      recurrence patterns with image-defined "signatures" and "habitats" was revealed.
      These image-defined "signatures" and "habitats" can be used to guide stereotactic
      tissue biopsy for genetic and mutation status analysis and to analyze for
      prediction of treatment outcomes, e.g., patterns of failure.

PMID- 29181434
TI  - Androgen receptor (AR) cistrome in prostate differentiation and cancer
      progression.
AB  - Despite the progress in development of better AR-targeted therapies for prostate
      cancer (PCa), there is no curative therapy for castration-resistant prostate
      cancer (CRPC). Therapeutic resistance in PCa can be characterized in two broad
      categories of AR therapy resistance: the first and most prevalent one involves
      restoration of AR activity despite AR targeted therapy, and the second one
      involves tumor progression despite blockade of AR activity. As such AR remains
      the most attractive drug target for CRPC. Despite its oncogenic role, AR
      signaling also contributes to the maturation and differentiation of prostate
      luminal cells during development. Recent evidence suggests that AR cistrome is
      altered in advanced PCa. Alteration in AR may result from AR amplification,
      alternative splicing, mutations, post-translational modification of AR, and
      altered expression of AR co-factors. We reasoned that such alterations would
      result in the transcription of disparate AR target genes and as such may
      contribute to the emergence of castration-resistance. In the present study, we
      evaluated the expression of genes associated with canonical or non-canonical AR
      cistrome in relationship with PCa progression and prostate development by
      analyzing publicly available datasets. We discovered a transcription switch from
      canonical AR cistrome target genes to the non-canonical AR cistrome target genes
      during PCa progression. Using Gene Set Enrichment Analysis (GSEA), we discovered
      that canonical AR cistrome target genes are enriched in indolent PCa patients and
      the loss of canonical AR cistrome is associated with tumor metastasis and poor
      clinical outcome. Analysis of the datasets involving prostate development,
      revealed that canonical AR cistrome target genes are significantly enriched in
      prostate luminal cells and can distinguish luminal cells from basal cells,
      suggesting a pivotal role for canonical AR cistrome driven genes in prostate
      development. These data suggest that the expression of canonical AR cistrome
      related genes play an important role in maintaining the prostate luminal cell
      identity and might restrict the lineage plasticity observed in lethal PCa.
      Understanding the molecular mechanisms that dictate AR cistrome may lead to
      development of new therapeutic strategies aimed at restoring canonical AR
      cistrome, rewiring the oncogenic AR signaling and overcome resistance to AR
      targeted therapies.

PMID- 29181435
TI  - Organoid culture of human prostate cancer cell lines LNCaP and C4-2B.
AB  - Organoids mimic the architecture and functions of a small organ. Organoid culture
      technique has been rapidly accepted by all research communities during the past
      decade to study stem cells, organ development and function, and patient-specific
      diseases. A protocol for organoid culture of human and mouse prostate epithelial
      and cancer tissues has been reported. However, organoid culture of the commonly
      used human prostate cancer cell lines has yet to be established. We followed the
      published protocol and performed organoid culture of LNCaP and C4-2B cells in
      MatrigelTM and organoid culture medium for 14 days. We found that both LNCaP and
      C4-2B cell lines formed organoids that presented glandular structures. The cells
      within the organoids were androgen receptor-positive adenocarcinoma cells, but
      not p63-positive basal cells. The cells in the organoids responded to interleukin
      17A treatment differently from the cells in the monolayer culture. The present
      study suggests that LNCaP and C4-2B cells are able to form organoids under the
      defined organoid culture conditions.

PMID- 29181437
TI  - Clinical features of patients treated by peritoneal dialysis for over a decade.
AB  - BACKGROUND: Peritoneal dialysis (PD) is well-established as renal replacement
      therapy in end stage renal disease and has survival rates similar or better than
      hemodialysis (HD) for the initial years on dialysis therapy. However retention
      rate is lower due to higher technique failure rates than in HD and few patients
      stay on PD for more than 10 years (PD>10 yrs). Here we investigated clinical
      features characterizing PD>10 yrs patients. PATIENTS AND METHODS: In a single
      center study of 450 prevalent PD patients, 35 PD>10 yrs patients (n=35) were
      compared with patients (n=415) who had been on PD for shorter periods of time in
      terms of clinical characteristics. Peritoneal transport, blood pressure, solute
      clearance, nutrition status, and blood calcium, phosphate and parathyroid hormone
      levels were measured dialysis start and, in PD>10 yrs patients, also after 5 and
      10 years of PD. RESULTS: The PD>10 yrs patients differed from the other PD
      patients in that (1) the proportion of women was higher; (2) body mass index
      (BMI) was lower; (3) there was no patient with diabetic nephropathy as primary
      diagnosis; (4) the incidence of peritonitis was lower; (5) glomerular filtration
      rate was higher; and (6) parathyroid hormone (PTH) levels were lower in those
      with decade-long PD treatment. In PD>10 yrs patients, serum albumin was
      maintained at a high level throughout the 10 year follow up; hemoglobin levels
      after 5 and 10 years of PD were higher than at the beginning of the treatment;
      blood calcium and phosphate concentrations were maintained at acceptable levels;
      while the dialysate/plasma ratio of creatinine, D/P-value, increased during the
      decade-long PD treatment. CONCLUSIONS: Patients receiving PD>10 years had lower
      incidence of peritonitis, lower BMI, adequate control of blood calcium and
      phosphate levels and solute clearance, and were more often women than PD patients
      treated for shorter periods of time.

PMID- 29181438
TI  - Parsley! Mechanism as antiurolithiasis remedy.
AB  - Parsley is a medicinal plant used widely in urolithiasis. The present study aimed
      to evaluate the antiurolithiatic effect of parsley and its mechanism. 24 rats
      divided into four groups: group A (negative control), group B (positive control),
      group C (cystone(r) group) and group D (parsley group). Group B were treated with
      EG and Ammonium chloride (AC). Group C were treated as B plus cystone(r) and
      group D was treated as B plus parsley. The period of experiment was 15 days.
      Urine samples were analysis on days 0 and 15 days. Kidneys of rats from all
      groups were removed, and histopathologically examined. The kidnies of parsley
      treated group appeared mostly to be calculi-free (less CaOx) even better than the
      cystone treated group. CaOx crystals was significantly lower both in histological
      sections and in urine samples in parsley treated group. We further investigated
      the mechanism of parsley by adding another 6 rats. The latter treated by parsley
      only after adaptation period. We found significant increase in urine volume and
      pH in parsley treated rats compared to negative control. We concluded that
      parsley acts as antiurolithiatic drug through decreasing urinary calcium
      excretion, increasing urinary pH, dieresis, decreasing urinary protein excretion
      and its nephroprtective activity. We recommended to use it in pharmaceutical
      forms as it is safe and effective as antiurolithiasis remedy.

PMID- 29181436
TI  - Molecular mechanisms involving prostate cancer racial disparity.
AB  - Prostate cancer (PCa) is the second leading cause of cancer-related deaths in the
      United States. The African (AA) descent has greater incidence and mortality rates
      of PCa as compared to Caucasian (CA) men. While socioeconomic differences across
      racial groups contribute to disparity in PCa, increasing evidence points that
      genetic and molecular alterations play important roles in racial disparities
      associated with PCa. In this review, we focus on genetic and molecular influences
      that contribute to racial disparity between AA and CA men including: androgen and
      estrogen receptor signaling pathways, growth factors, apoptotic proteins,
      genetic, genomic and epigenetic alterations. Future translational studies will
      identify prognostic and predictive biomarkers for AA PCa and assist in the
      development of new targeted-therapies specifically for AA men with PCa.

PMID- 29181439
TI  - Rest-activity circadian rhythms and bone mineral density in elderly men.
AB  - Background: Disrupted rest-activity circadian rhythm (RAR) patterns have been
      associated with poor health outcomes (i.e. diminished cognitive function,
      increased risk of dementia and falls). Circadian time cues in bone influence the
      differentiation of osteoblasts and osteoclasts, and bone turnover markers exhibit
      circadian variation; relationships between bone outcomes and RAR are emerging
      areas of research. We evaluated associations between RAR and areal bone mineral
      density (aBMD) at the total hip and femoral neck in older men from the
      Osteoporotic Fractures in Men (MrOS) cohort. We hypothesized that weaker RAR
      patterns would be associated with lower aBMD. Methods: MrOS is an ongoing
      prospective cohort study following ambulatory men >= 65 years (n = 5994) at 6
      U.S. clinics (baseline enrollment 3/2000-4/2002); participants for this analysis
      are from an ancillary study, Outcomes of Sleep Disorders in Older Men (MrOS
      Sleep). We included data from men who had technically adequate measures of RAR
      and aBMD at Sleep Visit 1 (12/2003-3/2005), with repeat aBMD at core Visit 3
      (3/2007-3/2009) (n = 2412; mean age at Sleep Visit 1: 75.7 +/- 5.2 years). aBMD
      was measured by dual energy x-ray absorptiometry (DXA). Actigraphs worn on the
      non-dominant wrist were used to collect circadian activity data over 4.8 +/- 0.8
      consecutive 24-hour periods. An extension of the traditional cosine curve was
      used to fit RAR to the activity data [Ancoli-Israel et al., 2003; Marler et al.,
      2006]. Six RAR parameters were evaluated: acrophase (time of peak activity),
      amplitude (rhythm strength), mesor (mean of activity fitted curve), pseudo F
      statistic (overall circadian rhythmicity of rest and activity), alpha statistic
      (daytime to nighttime activity ratio), and beta statistic (daytime activity).
      Associations between RAR and aBMD (Sleep Visit 1), and RAR and DeltaaBMD (Sleep
      Visit 1-Visit 3) were assessed with generalized linear models. Covariates
      included age, clinic site, physical activity, race, comorbidity, body mass index
      (BMI), smoking, alcohol, caffeine, beta blocker use, serum 25(OH) vitamin D and
      urinary melatonin and calcium. Results: Pseudo F-statistic was significantly
      associated with total hip aBMD (p-trend = 0.009), femoral neck aBMD (p-trend =
      0.007) and total hip DeltaaBMD (p-trend = 0.017) in minimally adjusted models but
      not after multivariate (MV) adjustment. Alpha statistic was significantly
      associated with femoral neck aBMD (p-trend = 0.029) and femoral neck DeltaaBMD (p
      trend = 0.019) in minimally adjusted models; significance was retained in the
      femoral neck DeltaaBMD model (p-trend = 0.034) after MV adjustment. There were no
      consistent, significant associations between the other RAR variables and aBMD or
      DeltaaBMD. Conclusions: The data demonstrate modest associations between overall
      circadian rhythmicity of rest and activity (measured by pseudo F-statistic), as
      well as daytime to nighttime activity ratio (measured by alpha statistic), aBMD
      and DeltaaBMD, but adjustment for covariates related to lifestyle, BMI and
      comorbidities attenuated most of these associations. These results suggest that
      RAR patterns are not independently associated with aBMD or four-year DeltaaBMD at
      the total hip or femoral neck in older men, but additional research is needed.

PMID- 29181440
TI  - Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone
      Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria.
AB  - Dexamethasone is widely used in both veterinary and human medical practices.
      However, it seems to cause some deleterious effects on pregnancy probably by
      causing changes in the reproductive hormone levels and their corresponding
      receptor concentrations. This study investigated the effects of dexamethasone on
      these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2
      rams were used for this study. Pregnancies were achieved by natural mating after
      estrus synchronization. Dexamethasone was administered at 0.25 mg/kg body weight
      on days 1, 3, and 5 during first trimester; days 51, 53, and 55 during second
      trimester; and days 101, 103, and 105 during the third trimester. Blood samples
      were collected biweekly for hormonal assay. Uterine biopsies were harvested
      through caesarean section for immunohistochemical analysis. Results showed that
      dexamethasone significantly (p < 0.05) decreased progesterone concentrations and
      caused abortion in Yankasa sheep but had no significant (p > 0.05) effect on
      estrogen, while progesterone receptors (PR) were upregulated. The abortion could
      probably be due to decreased progesterone concentrations as a consequence of the
      adverse effects on placenta. The PR upregulation may be a compensatory mechanism
      to increase progesterone sensitivity. It was concluded that dexamethasone should
      not be used in advanced pregnancy in Yankasa sheep.

PMID- 29181441
TI  - The Severity of Retinopathy in the Extremely Premature Infants.
AB  - Objective: We aimed to investigate the incidence and the severity of retinopathy
      of extremely premature infants and to evaluate the risk factors and outcome of
      the cases. Materials and Methods: Out of 200 premature births, we retrospectively
      reviewed 9 cases that developed ROP. We excluded cases where ROP developed in
      newborns > 30 weeks of gestational age and cases where medical notes were
      unavailable or incomplete. Topical drops of cyclopentolate 1% and phenylephrine
      5% were instilled and fundoscopy was performed using a direct ophthalmoscope.
      Results: The incidence of ROP was 4.5% in the 9-year period. The infants were
      divided into two groups. Group 1 included premature infants <=27 weeks of age and
      Group 2 included those >27 weeks but <= 30 weeks of age. We found that the
      infants of Group 1 showed advanced stages of ROP in comparison to Group 2. Out of
      18 eyes, 11 eyes had stage 3 ROP and they were all found in Group 1 (100% of
      cases). Conclusion: The severity of ROP was associated with earlier gestational
      age, lower birth weight, and oxygen supplementation. Constant cooperation between
      physicians and nursing staff is necessary to avoid undetected cases and further
      prevent ROP related blindness.

PMID- 29181442
TI  - Weak Middle-Ear-Muscle Reflex in Humans with Noise-Induced Tinnitus and Normal
      Hearing May Reflect Cochlear Synaptopathy.
AB  - Chronic tinnitus is a prevalent hearing disorder, and yet no successful
      treatments or objective diagnostic tests are currently available. The aim of this
      study was to investigate the relationship between the presence of tinnitus and
      the strength of the middle-ear-muscle reflex (MEMR) in humans with normal and
      near-normal hearing. Clicks were used as test stimuli to obtain a wideband
      measure of the effect of reflex activation on ear-canal sound pressure. The
      reflex was elicited using a contralateral broadband noise. The results show that
      the reflex strength is significantly reduced in individuals with noise-induced
      continuous tinnitus and normal or near-normal audiometric thresholds compared
      with no-tinnitus controls. Due to a shallower growth of the reflex strength in
      the tinnitus group, the difference between the two groups increased with
      increasing elicitor level. No significant difference in the effect of tinnitus on
      the strength of the middle-ear muscle reflex was found between males and females.
      The weaker reflex could not be accounted for by differences in audiometric
      hearing thresholds between the tinnitus and control groups. Similarity between
      our findings in humans and the findings of a reduced middle-ear muscle reflex in
      noise-exposed animals suggests that noise-induced tinnitus in individuals with
      clinically normal hearing may be a consequence of cochlear synaptopathy, a loss
      of synaptic connections between inner hair cells (IHCs) in the cochlea and
      auditory-nerve (AN) fibers that has been termed hidden hearing loss.

PMID- 29181443
TI  - Networks of global bird invasion altered by regional trade ban.
AB  - Wildlife trade is a major pathway for introduction of invasive species worldwide.
      However, how exactly wildlife trade influences invasion risk, beyond the
      transportation of individuals to novel areas, remains unknown. We analyze the
      global trade network of wild-caught birds from 1995 to 2011 as reported by CITES
      (Convention on International Trade in Endangered Species of Wild Fauna and
      Flora). We found that before the European Union ban on imports of wild-caught
      birds, declared in 2005, invasion risk was closely associated with numbers of
      imported birds, diversity of import sources, and degree of network centrality of
      importer countries. After the ban, fluxes of global bird trade declined sharply.
      However, new trade routes emerged, primarily toward the Nearctic, Afrotropical,
      and Indo-Malay regions. Although regional bans can curtail invasion risk
      globally, to be fully effective and prevent rerouting of trade flows, bans should
      be global.

PMID- 29181444
TI  - Climate change and water management in the biblical city of Dan.
AB  - Global climate change has sharpened focus on the social and economic challenges
      associated with water deficits, particularly in regions where anthropogenic
      demands exceed supply. This modern condition was also experienced by the people
      of ancient western Asia, where chronic water shortages were accentuated by
      recurrent droughts. However, human societies may react to climate change,
      particularly desiccation, in different ways depending on specific local
      conditions. Focusing on the biblical site of Tel Dan (present-day Israel), we
      show the effects of severe precipitation decline in an environment that was well
      watered and fertile even in times of drought. Such local niches of prosperity
      became attractive targets for predation when food resources became scarce in
      surrounding rain-fed areas. We propose that predation forced urban populations to
      either flee or adopt new subsistence strategies. Predation and abandonment, even
      if only partial, led to the poor maintenance of water networks in and around the
      city. Once stagnant water surrounded the area, water-borne disease proliferated.
      Our study shows how climate changes can disrupt social and political structures,
      cause water system management to collapse, and facilitate marshland expansion.

PMID- 29181445
TI  - Artificially lit surface of Earth at night increasing in radiance and extent.
AB  - A central aim of the "lighting revolution" (the transition to solid-state
      lighting technology) is decreased energy consumption. This could be undermined by
      a rebound effect of increased use in response to lowered cost of light. We use
      the first-ever calibrated satellite radiometer designed for night lights to show
      that from 2012 to 2016, Earth's artificially lit outdoor area grew by 2.2% per
      year, with a total radiance growth of 1.8% per year. Continuously lit areas
      brightened at a rate of 2.2% per year. Large differences in national growth rates
      were observed, with lighting remaining stable or decreasing in only a few
      countries. These data are not consistent with global scale energy reductions but
      rather indicate increased light pollution, with corresponding negative
      consequences for flora, fauna, and human well-being.

PMID- 29181446
TI  - Discrete False-Discovery Rate Improves Identification of Differentially Abundant
      Microbes.
AB  - Differential abundance testing is a critical task in microbiome studies that is
      complicated by the sparsity of data matrices. Here we adapt for microbiome
      studies a solution from the field of gene expression analysis to produce a new
      method, discrete false-discovery rate (DS-FDR), that greatly improves the power
      to detect differential taxa by exploiting the discreteness of the data.
      Additionally, DS-FDR is relatively robust to the number of noninformative
      features, and thus removes the problem of filtering taxonomy tables by an
      arbitrary abundance threshold. We show by using a combination of simulations and
      reanalysis of nine real-world microbiome data sets that this new method
      outperforms existing methods at the differential abundance testing task,
      producing a false-discovery rate that is up to threefold more accurate, and
      halves the number of samples required to find a given difference (thus increasing
      the efficiency of microbiome experiments considerably). We therefore expect DS
      FDR to be widely applied in microbiome studies. IMPORTANCE DS-FDR can achieve
      higher statistical power to detect significant findings in sparse and noisy
      microbiome data compared to the commonly used Benjamini-Hochberg procedure and
      other FDR-controlling procedures.

PMID- 29181447
TI  - Increased Biosynthetic Gene Dosage in a Genome-Reduced Defensive Bacterial
      Symbiont.
AB  - A symbiotic lifestyle frequently results in genome reduction in bacteria; the
      isolation of small populations promotes genetic drift and the fixation of
      deletions and deleterious mutations over time. Transitions in lifestyle,
      including host restriction or adaptation to an intracellular habitat, are thought
      to precipitate a wave of sequence degradation events and consequent proliferation
      of pseudogenes. We describe here a verrucomicrobial symbiont of the tunicate
      Lissoclinum sp. that appears to be undergoing such a transition, with low coding
      density and many identifiable pseudogenes. However, despite the overall drive
      toward genome reduction, this symbiont maintains seven copies of a large
      polyketide synthase (PKS) pathway for the mandelalides (mnd), cytotoxic compounds
      that likely constitute a chemical defense for the host. There is evidence of
      ongoing degradation in a small number of these repeats-including variable
      borders, internal deletions, and single nucleotide polymorphisms (SNPs). However,
      the gene dosage of most of the pathway is increased at least 5-fold.
      Correspondingly, this single pathway accounts for 19% of the genome by length and
      25.8% of the coding capacity. This increased gene dosage in the face of
      generalized sequence degradation and genome reduction suggests that mnd genes are
      under strong purifying selection and are important to the symbiotic relationship.
      IMPORTANCE Secondary metabolites, which are small-molecule organic compounds
      produced by living organisms, provide or inspire drugs for many different
      diseases. These natural products have evolved over millions of years to provide a
      survival benefit to the producing organism and often display potent biological
      activity with important therapeutic applications. For instance, defensive
      compounds in the environment may be cytotoxic to eukaryotic cells, a property
      exploitable for cancer treatment. Here, we describe the genome of an uncultured
      symbiotic bacterium that makes such a cytotoxic metabolite. This symbiont is
      losing genes that do not endow a selective advantage in a hospitable host
      environment. Secondary metabolism genes, however, are repeated multiple times in
      the genome, directly demonstrating their selective advantage. This finding shows
      the strength of selective forces in symbiotic relationships and suggests that
      uncultured bacteria in such relationships should be targeted for drug discovery
      efforts.

PMID- 29181448
TI  - Direct PCR Offers a Fast and Reliable Alternative to Conventional DNA Isolation
      Methods for Gut Microbiomes.
AB  - The gut microbiome of animals is emerging as an important factor influencing
      ecological and evolutionary processes. A major bottleneck in obtaining microbiome
      data from large numbers of samples is the time-consuming laboratory procedures
      required, specifically the isolation of DNA and generation of amplicon libraries.
      Recently, direct PCR kits have been developed that circumvent conventional DNA
      extraction steps, thereby streamlining the laboratory process by reducing
      preparation time and costs. However, the reliability and efficacy of direct PCR
      for measuring host microbiomes have not yet been investigated other than in
      humans with 454 sequencing. Here, we conduct a comprehensive evaluation of the
      microbial communities obtained with direct PCR and the widely used Mo Bio
      PowerSoil DNA extraction kit in five distinct gut sample types (ileum, cecum,
      colon, feces, and cloaca) from 20 juvenile ostriches, using 16S rRNA Illumina
      MiSeq sequencing. We found that direct PCR was highly comparable over a range of
      measures to the DNA extraction method in cecal, colon, and fecal samples.
      However, the two methods significantly differed in samples with comparably low
      bacterial biomass: cloacal and especially ileal samples. We also sequenced 100
      replicate sample pairs to evaluate repeatability during both extraction and PCR
      stages and found that both methods were highly consistent for cecal, colon, and
      fecal samples (rs > 0.7) but had low repeatability for cloacal (rs = 0.39) and
      ileal (rs = -0.24) samples. This study indicates that direct PCR provides a fast,
      cheap, and reliable alternative to conventional DNA extraction methods for
      retrieving 16S rRNA data, which can aid future gut microbiome studies. IMPORTANCE
      The microbial communities of animals can have large impacts on their hosts, and
      the number of studies using high-throughput sequencing to measure gut microbiomes
      is rapidly increasing. However, the library preparation procedure in microbiome
      research is both costly and time-consuming, especially for large numbers of
      samples. We investigated a cheaper and faster direct PCR method designed to
      bypass the DNA isolation steps during 16S rRNA library preparation and compared
      it with a standard DNA extraction method. We used both techniques on five
      different gut sample types collected from 20 juvenile ostriches and sequenced
      samples with Illumina MiSeq. The methods were highly comparable and highly
      repeatable in three sample types with high microbial biomass (cecum, colon, and
      feces), but larger differences and low repeatability were found in the
      microbiomes obtained from the ileum and cloaca. These results will help
      microbiome researchers assess library preparation procedures and plan their
      studies accordingly.

PMID- 29181450
TI  - Cerebrospinal fluid markers to distinguish bacterial meningitis from cerebral
      malaria in children.
AB  - Background. Few hospitals in high malaria endemic countries in Africa have the
      diagnostic capacity for clinically distinguishing acute bacterial meningitis
      (ABM) from cerebral malaria (CM). As a result, empirical use of antibiotics is
      necessary. A biochemical marker of ABM would facilitate precise clinical
      diagnosis and management of these infections and enable rational use of
      antibiotics. Methods. We used label-free protein quantification by mass
      spectrometry to identify cerebrospinal fluid (CSF) markers that distinguish ABM
      (n=37) from CM (n=22) in Kenyan children. Fold change (FC) and false discovery
      rates (FDR) were used to identify differentially expressed proteins.
      Subsequently, potential biomarkers were assessed for their ability to
      discriminate between ABM and CM using receiver operating characteristic (ROC)
      curves. Results. The host CSF proteome response to ABM ( Haemophilusinfluenza and
      Streptococcuspneumoniae) is significantly different to CM. Fifty two proteins
      were differentially expressed (FDR<0.01, Log FC>=2), of which 83% (43/52) were
      upregulated in ABM compared to CM. Myeloperoxidase and lactotransferrin were
      present in 37 (100%) and 36 (97%) of ABM cases, respectively, but absent in CM
      (n=22). Area under the ROC curve (AUC), sensitivity, and specificity were
      assessed for myeloperoxidase (1, 1, and 1; 95% CI, 1-1) and lactotransferrin
      (0.98, 0.97, and 1; 95% CI, 0.96-1). Conclusion. Myeloperoxidase and
      lactotransferrin have a high potential to distinguish ABM from CM and thereby
      improve clinical management. Their validation requires a larger cohort of samples
      that includes other bacterial aetiologies of ABM.

PMID- 29181449
TI  - Transcriptome Sequencing Reveals Novel Candidate Genes for Cardinium hertigii
      Caused Cytoplasmic Incompatibility and Host-Cell Interaction.
AB  - Cytoplasmic incompatibility (CI) is an intriguing, widespread, symbiont-induced
      reproductive failure that decreases offspring production of arthropods through
      crossing incompatibility of infected males with uninfected females or with
      females infected with a distinct symbiont genotype. For years, the molecular
      mechanism of CI remained unknown. Recent genomic, proteomic, biochemical, and
      cell biological studies have contributed to understanding of CI in the
      alphaproteobacterium Wolbachia and implicate genes associated with the WO
      prophage. Besides a recently discovered additional lineage of
      alphaproteobacterial symbionts only moderately related to Wolbachia, Cardinium
      (Bacteroidetes) is the only other symbiont known to cause CI, and genomic
      evidence suggests that it has very little homology with Wolbachia and evolved
      this phenotype independently. Here, we present the first transcriptomic study of
      the CI Cardinium strain cEper1, in its natural host, Encarsia suzannae, to detect
      important CI candidates and genes involved in the insect-Cardinium symbiosis.
      Highly expressed transcripts included genes involved in manipulating
      ubiquitination, apoptosis, and host DNA. Female-biased genes encoding ribosomal
      proteins suggest an increase in general translational activity of Cardinium in
      female wasps. The results confirm previous genomic analyses that indicated that
      Wolbachia and Cardinium utilize different genes to induce CI, and transcriptome
      patterns further highlight expression of some common pathways that these bacteria
      use to interact with the host and potentially cause this enigmatic and
      fundamental manipulation of host reproduction. IMPORTANCE The majority of insects
      carry maternally inherited intracellular bacteria that are important in their
      hosts' biology, ecology, and evolution. Some of these bacterial symbionts cause a
      reproductive failure known as cytoplasmic incompatibility (CI). In CI, the mating
      of symbiont-infected males and uninfected females produces few or no daughters.
      The CI symbiont then spreads and can have a significant impact on the insect host
      population. Cardinium, a bacterial endosymbiont of the parasitoid wasp Encarsia
      in the Bacteroidetes, is the only bacterial lineage known to cause CI outside the
      Alphaproteobacteria, where Wolbachia and another recently discovered CI symbiont
      reside. Here, we sought insight into the gene expression of a CI-inducing
      Cardinium strain in its natural host, Encarsia suzannae. Our study provides the
      first insights into the Cardinium transcriptome and provides support for the
      hypothesis that Wolbachia and Cardinium target similar host pathways with
      distinct and largely unrelated sets of genes.

PMID- 29181451
TI  - Impact of trichiasis surgery on daily living: A longitudinal study in Ethiopia.
AB  - Background: Trachomatous trichiasis (TT) may lead to disability, impeding
      productive activities, resulting in loss of income. This study was conducted to
      determine if trichiasis surgery improves participation in productive and leisure
      activities, and ability to perform activities without difficulty or assistance.
      Methods: We recruited 1000 adults with trichiasis (cases) and 200 comparison
      participants, matched to every fifth trichiasis case on age (+/- two years), sex
      and location. The 'Stylised Activity List' tool, developed for the World Bank
      Living Standard Measurement Survey, was adapted to collect data on activity in
      the last week (participation in activity, difficulty with activity, requirement
      of assistance for activity), at baseline and 12 months later. All trichiasis
      cases received trichiasis surgery at baseline. Random effect logistic regression
      was used to compare cases and comparison participants. Results: There was strong
      evidence that trichiasis surgery substantially improves the ability of trichiasis
      cases to perform all the productive and leisure activities investigated without
      difficulty, with large increases in processing agricultural products, 21.1% to
      87.0% (p<0.0001), farming, 19.1% to 82.4% (p<0.0001), and fetching wood, 25.3% to
      86.0% (p<0.0001). Similarly, there was a significant increase in the proportion
      of cases who could perform activities without assistance, with the largest
      increases in animal rearing 54.2% to 92.0% (p<0.0001) and farming 73.2% to 96.4%
      (p<0.0001). There was no change in the proportion of comparison participants
      performing activities without difficulty or assistance. The change in most of the
      activities in cases was independent of visual acuity improvement and recurrent TT
      at 12 months. One year after trichiasis surgery, the proportion of cases
      reporting ocular pain reduced from 98.9% to 33.7% (p<0.0001). Conclusions: Eyelid
      surgery for TT improves functional capabilities regardless of vision gains. These
      data lend strong support to the view that TT surgery improves function and
      contributes to improved household income and wealth.

PMID- 29181452
TI  - Prevalences of inherited red blood cell disorders in pregnant women of different
      ethnicities living along the Thailand-Myanmar border.
AB  - Background: Inherited red blood cell disorders are prevalent in populations
      living in malaria endemic areas; G6PD deficiency is associated with oxidant
      induced haemolysis and abnormal haemoglobin variants may cause chronic anaemia.
      In pregnant women, microcytic anaemia caused by haemoglobinopathies mimics iron
      deficiency, complicating diagnosis and treatment. Anaemia during pregnancy is
      associated with morbidity and mortality. The aim of this study was to
      characterise the prevalence of G6PD deficiency and haemoglobinopathies  among the
      pregnant population living along the Thailand-Myanmar border. Pregnant women
      attending antenatal clinics in this area belong to several distinct ethnic
      groups. Methods: Data were available for 13,520 women attending antenatal care
      between July 2012 and September 2016. Screening for G6PD deficiency was done by
      fluorescent spot test routinely. G6PD genotyping and quantitative phenotyping by
      spectrophotometry were analysed in a subsample of women. Haemoglobin variants
      were diagnosed by HPLC or capillary electrophoresis and molecular methods. The
      prevalence and distribution of inherited red blood cell disorders was analysed
      with respect to ethnicity. Results: G6PD deficiency was common, especially in the
      Sgaw Karen ethnic group, in whom the G6PD Mahidol variant allele frequency was
      20.7%. Quantitative G6PD phenotyping showed that 60.5% of heterozygous women had
      an intermediate enzymatic activity between 30% and 70% of the population median.
      HbE, beta-thalassaemia trait and Hb Constant Spring were found overall in 15.6%
      of women. Only 45.2% of women with low percentage of HbA 2 were carriers of
      mutations on the alpha globin genes. Conclusions: Distribution of G6PD and
      haemoglobin variants varied among the different ethnic groups, but the prevalence
      was generally high throughout the cohort. These findings encourage the
      implementation of an extended program of information and genetic counselling to
      women of reproductive age and will help inform future studies and current
      clinical management of anaemia in the pregnant population in this region.

PMID- 29181453
TI  - Supporting surveillance capacity for antimicrobial resistance: Laboratory
      capacity strengthening for drug resistant infections in low and middle income
      countries.
AB  - Development of antimicrobial resistance (AMR) threatens our ability to treat
      common and life threatening infections. Identifying the emergence of AMR requires
      strengthening of surveillance for AMR, particularly in low and middle-income
      countries (LMICs) where the burden of infection is highest and health systems are
      least able to respond. This work aimed, through a combination of desk-based
      investigation, discussion with colleagues worldwide, and visits to three
      contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing
      models and surveillance systems for AMR, to examine what worked and what did not
      work. Current capacity for AMR surveillance varies in LMICs, but and systems in
      development are focussed on laboratory surveillance. This approach limits
      understanding of AMR and the extent to which laboratory results can inform local,
      national and international public health policy. An integrated model, combining
      clinical, laboratory and demographic surveillance in sentinel sites is more
      informative and costs for clinical and demographic surveillance are
      proportionally much lower. The speed and extent to which AMR surveillance can be
      strengthened depends on the functioning of the health system, and the resources
      available. Where there is existing laboratory capacity, it may be possible to
      develop 5-20 sentinel sites with a long term view of establishing comprehensive
      surveillance; but where health systems are weaker and laboratory infrastructure
      less developed, available expertise and resources may limit this to 1-2 sentinel
      sites. Prioritising core functions, such as automated blood cultures, reduces
      investment at each site. Expertise to support AMR surveillance in LMICs may come
      from a variety of international, or national, institutions. It is important that
      these organisations collaborate to support the health systems on which AMR
      surveillance is built, as well as improving technical capacity specifically
      relating to AMR surveillance. Strong collaborations, and leadership, drive
      successful AMR surveillance systems across countries and contexts.

PMID- 29181454
TI  - Effectiveness of Laboratory Practices to Reducing Patient Misidentification Due
      to Specimen Labeling Errors at the Time of Specimen Collection in Healthcare
      Settings: LMBPTM Systematic Review.
AB  - Background: Specimen labeling errors have long plagued the laboratory industry
      putting patients at risk of transfusion-related death, medication errors,
      misdiagnosis, and patient mismanagement. Many interventions have been implemented
      and deemed to be effective in reducing sample error rates. The objective of this
      review was to identify and evaluate the effectiveness of laboratory practices/
      interventions to develop evidence based recommendations for the best laboratory
      practices to reduce labeling errors. Content: The standardized LMBPTM A-6 methods
      were used to conduct this systematic review. Total evidence included 12 studies
      published during the time periods of 1980 to September 2015. Combined data from
      seven studies found that the interventions developed as a result of improved
      communication and collaboration between the laboratory and clinical staff
      resulted in substantial decrease in specimen labeling errors (Median relative
      percent change in labeling errors: -75.86; IQI: -84.77, -58.00). Further data
      from subset of four studies showed a significant decrease in specimen labeling
      errors after the institution of the standardized specimen labeling protocols
      (Median relative percent decrease in specimen labeling errors: -72.45; IQI: 
      83.25, -46.50). Summary: Based on the evidence included in this review, the
      interventions that enhance the communication and collaboration between laboratory
      and healthcare professionals can decrease the specimen identification errors in
      healthcare settings. However, more research is needed to make the conclusion on
      the effectiveness of other evaluated practices in this review including training
      and education of the specimen collection staff, audit and feedback of labeling
      errors, and implementation of new technology (other than barcoding).

PMID- 29181455
TI  - The New Definition of Oral Health and Relationship between Oral Health and
      Quality of Life.
AB  - FDI World Dental Federation, which has 200 dental association members in some 130
      countries, is the official representative body and voice of more than 1 million
      clinicians worldwide. It set itself the task of creating a new definition for
      oral health as a baseline to develop tools to measure oral health and related
      indicators. The definition allows FDI to position oral health within the global
      health agenda in areas such as quality of life and wellbeing and the challenge of
      an ageing population worldwide. Furthermore, it provides an impetus for FDI
      activities in favour of worldwide periodontal health.

PMID- 29181456
TI  - A Review of Excessive Sugar Metabolism on Oral and General Health.
AB  - Stomatologists and dental practitioners, as they are called in different parts of
      the world according to tradition and history, are basically physicians who
      specialise in the study and treatment of diseases of the mouth and surrounding
      structures. They have always been outstanding in advocating the reduction of
      sugar consumption, mainly due to its direct connection to the pathogenesis of
      dental caries. Increasingly, it has come to the attention of researchers,
      epidemiologists and many healthcare workers and professionals that excessive
      consumption of sugar is also closely tied to the increase in tandem of our
      current major health issues like obesity, diabetes, heart, liver and kidney
      disease, and a host of other associated ailments. This development of current
      health crises throughout the world wherever traditional diets are replaced with
      modern fast food diets, which are usually packed with hidden, added refined
      sugars, is extremely troubling. It becomes all the more urgent and incumbent upon
      clinicians and stomatologists throughout the world to redouble their efforts to
      reduce and even eliminate the excessive consumption of added or extrinsic or
      secondary or hidden sugars to food and drinks. It will not only be to reduce
      dental caries, but also to reduce the many systemic and organ diseases associated
      with added sugars and which also exacerbate many oral diseases. This review is to
      give a basic history of sugar, the current understanding of sugar metabolism and
      the developing literature and research on the impact of sugar consumption on oral
      and overall health, as the mouth cannot be divorced from the body and vice versa.
      The author hopes to kick-start more research into this area that will result in
      various positive developments in the food and drink industry and persuade
      stakeholders to comprehensively address this universal health crisis that is
      closely tied to excessive consumption of added sugar in all its forms.

PMID- 29181457
TI  - Comparison of Real-Time Quantitative PCR with a Chairside Test for Streptococcus
      Mutans Assessment.
AB  - OBJECTIVE: To compare two methods for Streptococcus mutans detection and
      quantification in the human oral cavity: a chairside commercial test and a
      molecular-based real-time quantitative polymerase chain reaction (qPCR) method.
      METHODS: A total of 688 whole saliva samples were collected from 344 children
      aged 3 and 5 and their biological mothers. Caries status was examined using a
      World Health Organisation survey method. S. mutans levels were measured using the
      Dentocult SM Strip mutans test and scored as colony forming units per millilitre
      of saliva. Meanwhile, bacterial genomic DNA was extracted from the saliva, qPCR
      was performed with S. mutans species-specific primers, and absolute S. mutans DNA
      concentrations were obtained and scored as micrograms of DNA per millilitre of
      saliva. The two methods were compared for sensitivity, specificity, agreement and
      correlation with caries status. RESULTS: Significantly more participants tested
      positive for S. mutans by qPCR than in the chairside SM Strip test (82.4% vs
      71.4%). When only the highest and lowest test scores were considered, the
      agreement between the two methods assessing S. mutans colonisation was 0.956.
      Children with high levels of S. mutans in their saliva were six to eight times
      more likely to develop dental caries at 5 years old. CONCLUSION: The study
      provides new evidence supporting the use of the chairside SM Strip test or the
      qPCR assay for the detection and quantification of S. mutans colonisation in
      saliva as the analytical approach of choice for caries risk assessment in
      clinical and epidemiological studies.

PMID- 29181458
TI  - Minimally Invasive Crestal Sinus Lift Technique and Simultaneous Implant
      Placement.
AB  - OBJECTIVE: To evaluate the effectiveness and clinical results of a new crestal
      sinus lift technique used to elevate the sinus floor simultaneously with bone
      grafts and implant placement. METHODS: Eleven patients underwent this crestal
      sinus lift technique performed using an SCA KIT. The mean residual bone height
      was 6.4 mm (range: 4.1 mm to 8.6 mm). Bio-Oss collagen was used as the graft
      material, and 12 implants were simultaneously placed after sinus augmentation.
      Radiographic and clinical examinations were conducted during follow-up. RESULTS:
      All procedures were successfully performed with no obvious Schneiderian membrane
      perforation. The sinus floor was augmented with a mean height of 4.8 mm (range:
      2.8 to 7.4 mm). Twelve implants healed uneventfully with healing abutments. Peri
      implant marginal bone was stable, with a mean follow-up of 49.4 months (range: 33
      to 71 months). No complications were observed during follow-up. CONCLUSION:
      According to the limited data collected in this study, the novel crestal sinus
      lift approach could effectively lift the sinus floor and reduce the incidence of
      postoperative complications. Additional cases with long-term follow-up are needed
      to confirm and improve this crestal sinus lift technique.

PMID- 29181459
TI  - Gallium-67 Scintigraphy in Differential Diagnosis of Malignant Tumours from Non
      Tumorous Lesions of the Maxilla.
AB  - OBJECTIVE: To assess the gallium-67 (67Ga) scintigraphy in differential diagnosis
      of malignant tumours from non-tumorous lesions of the maxilla. METHODS: Nineteen
      patients with malignant tumours (six cases of squamous cell carcinoma and one
      case of malignant melanoma) and non-tumorous lesions (seven cases of maxillary
      sinusitis and five cases of postoperative maxillary changes) in the maxilla
      underwent 67Ga and bone scintigraphy with CT and MRI. The statistical analysis
      with respect to comparison between imaging features of 67Ga and bone scintigraphy
      and maxillary lesions was performed with the Pearson's chi-squared test. RESULTS:
      67Ga scintigraphy for six of the seven patients with malignant tumours in the
      maxilla was positive (85.7%), 0 of 12 patients with non-tumorous lesions were
      positive (0%) (P = 0.000). Bone scintigraphy for six out of seven patients with
      malignant tumours was positive (85.7%), 10 of 12 patients with non-tumorous
      lesions were positive (83.3%) (P = 0.891). CONCLUSION: 67Ga scintigraphy was
      useful for detection of malignant tumours in the maxilla. However, bone
      scintigraphy was not an effective technique for interpretation of malignant
      tumours, maxillary sinusitis and postoperative change in the maxilla.

PMID- 29181460
TI  - Electrode Placing Sites affect Pulp Vitality Test of Human Incisors and
      Premolars.
AB  - OBJECTIVE: To investigate electric pulp test thresholds at different sites on
      healthy incisors and premolars and determine appropriate test sites. METHODS:
      Overall, 47 volunteers aged 20 to 30 years were recruited, and 163 incisors and
      140 premolars were tested at several sites with an Electric Pulp Tester. One-way
      analysis of variance and a Tukey test were used to analyse the threshold values
      among different tooth types and sites. RESULTS: The lowest threshold value for
      incisors was identified on the incisal edge. The difference of threshold on the
      incisal edge and other sites was statistically significant in mandibular
      incisors. For maxillary premolars and the mandibular second premolar, the lowest
      response was obtained with the tester tip on the lingual slope of the buccal
      cusp. For the mandibular first premolar, the response at the lingual slope of the
      buccal cusp, as the second lowest, was slightly higher than that at the buccal
      cusp. CONCLUSION: The incisal edge for incisors and the lingual slope of the
      buccal cusp for premolars was favoured as the optimal sites for electric pulp
      test.

PMID- 29181461
TI  - Platelet-Rich Fibrin with Bone Grafts for Regeneration of Bony Defect following
      Extraction of Supernumerary Teeth: A Case Report.
AB  - Supernumerary teeth are hyperdontic variants due to abnormalities during tooth
      development. Here, we report a case on regeneration of bony defect, which ensued
      following extraction of two supernumerary teeth in the mandibular premolar
      region, using a combination of bone grafts and platelet-rich fibrin. To the best
      of our knowledge, it is the first time synergistic use of biomaterials with bone
      grafts have been used for this type of management.

PMID- 29181462
TI  - Chemical amplification accelerates reactive oxygen species triggered polymeric
      degradation.
AB  - Chemical amplification is a known strategy for improving the sensitivity of
      stimuli-responsive polymers. However, the chemical amplification effect has never
      been fully examined. Many questions remain about its mechanism and efficacy,
      obstructing its further implementation. Here, we design and demonstrate a
      reactive oxygen species (ROS) responsive polymer (ROS-ARP) with a chemical
      amplification strategy to dismiss these concerns. The ROS-ARP is designed to
      change the hydrophilicity by ROS, revealing a carboxylic acid, which also
      catalyzes ketal hydrolysis along the polymer backbone. The chemical amplification
      strategy of ROS-ARP accelerated the polymer degradation up to 17 fold compared to
      a previously reported ROS-responsive polymer. To investigate the mechanism behind
      this increased acceleration, we compared the degradation kinetics in various
      environments. Additionally, other effects such as hydrophilicity changes were
      excluded. The accelerated degradation of ROS-ARP is evaluated as a potential drug
      delivery system, demonstrating on-demand cargo release from the formulated
      polymeric particles.

PMID- 29181464
TI  - Exploration of cell division times during bacterial cytokinesis.
AB  - Filamenting temperature-sensitive mutant Z (FtsZ), an essential cell division
      protein in bacteria, has recently emerged as an important and exploitable
      antibacterial target. The perturbation of FtsZ assembly is found to have an
      effect on cell cytokinesis and cell survival. Cell division time is an important
      physical parameter in cell cytokinesis. Here, the theoretical framework that has
      been developed by combining a phase field model for rod-shaped cells with a
      kinetic description for FtsZ ring maintenance is extended to explore cell
      division times during bacterial cytokinesis. The cell division times of around 72
      s in the numerical studies have the same magnitude as the division time of
      several minutes observed physiologically. The dependence of the cell division
      time on parameters such as the initial state of rod-shaped cells and various
      kinetic rates of FtsZ assembly dynamics is thoroughly investigated. The
      theoretical analysis of the relations between the cell division time and these
      parameters is found to coincide well with the numerical calculated results.

PMID- 29181465
TI  - Strain engineering of phonon thermal transport properties in monolayer 2H-MoTe2.
AB  - The effect of strain on the phonon properties such as phonon group velocity,
      phonon anharmonicity, phonon lifetime, and lattice thermal conductivity of
      monolayer 2H-MoTe2 is studied by solving the Boltzmann transport equation based
      on first principles calculations. The phonon thermal transport properties of the
      unstrained monolayer 2H-MoTe2 are compared to those of the strained case under
      different biaxial tensile strains. One of the common features of two-dimensional
      materials is the quadratic nature near the Gamma point of the out-of-plane phonon
      flexural mode that disappears by applying tensile strain. We find that the
      lattice thermal conductivity of the monolayer 2H-MoTe2 is very sensitive to
      strain, and the lattice thermal conductivity is reduced by approximately 2.5
      times by applying 8% biaxial tensile strain due to the reduction in phonon group
      velocities and phonon lifetime. We also analyze how the contribution of each mode
      to lattice thermal conductivity changes with tensile strain. These results
      highlight that tensile strain is a key parameter in engineering phonon thermal
      transport properties in monolayer 2H-MoTe2.

PMID- 29181466
TI  - Quantum stochastic trajectories: the Smoluchowski-Bohm equation.
AB  - Molecular systems are quantum systems, but the complete characterization of
      molecular motions within a fully quantum framework might appear to be an
      unfeasible task because it would require that the actual nuclear positions are
      established at any time. One would like to use a quantum molecular trajectory
      that defines the instantaneous nuclear positions and satisfies the predictions of
      quantum mechanics in terms of its statistical properties. Even though it can be
      proven that the single Bohm trajectory provides a representation of the quantum
      molecular trajectory, this solves the issue only on a theoretical ground: exact
      solutions of the Schrodinger-Bohm dynamical system are extremely computationally
      demanding. Therefore, we derive a stochastic equation of Smoluchowski type from
      the Schrodinger-Bohm dynamics, through projection operator techniques, in order
      to characterize the molecular motions of open quantum systems. The main quantum
      features of the motions emerge from the equilibrium distribution, i.e., the wave
      function's squared modulus integrated on the environment degrees of freedom.
      Furthermore, we verify the accuracy of the stochastic equation by comparing its
      predictions with those of the deterministic dynamics for a model system of six
      interacting harmonic oscillators. The indisputable advantage of this full quantum
      mechanical approach is that of representing the molecular dynamics, which
      controls important phenomena like vibrational relaxation, conformational
      transitions and activated processes, in a self consistent way and at the low
      computational cost of solving simple stochastic equations.

PMID- 29181468
TI  - Analysis of dispersive interactions at polymer/TiAlN interfaces by means of
      dynamic force spectroscopy.
AB  - The structural and electronic origins of the interactions between polycarbonate
      and sputter deposited TiAlN were analysed using a combined electron and force
      spectroscopic approach. Interaction forces were measured by means of dynamic
      force spectroscopy and the surface polarizability was analysed by X-ray
      photoelectron valence band spectroscopy. It could be shown that the adhesive
      interactions between polycarbonate and TiAlN are governed by van der Waals
      forces. Different surface cleansing and oxidizing treatments were investigated
      and the effect of the surface chemistry on the force interactions was analysed.
      Intense surface oxidation resulted in a decreased adhesion force by a factor of
      two due to the formation of a 2 nm thick Ti0.21Al0.45O surface oxide layer. The
      origin of the residual adhesion forces caused by the mixed Ti0.21Al0.45O surface
      oxide was clarified by considering the non-retarded Hamaker coefficients as
      calculated by Lifshitz theory, based on optical data from Reflection Electron
      Energy Loss Spectroscopy. This disclosed increased dispersion forces of
      Ti0.21Al0.45O due to the presence of Ti(iv) ions and related Ti 3d band optical
      transitions.

PMID- 29181469
TI  - A full-spectrum photocatalyst with strong near-infrared photoactivity derived
      from synergy of nano-heterostructured Er3+-doped multi-phase oxides.
AB  - The development of full-spectrum photocatalysts active in the near-infrared (NIR)
      region has gained increasing attention in the photodegradation of organic
      pollutants. Herein, we designed a full-spectrum photocatalyst with strong NIR
      photoactivity based on the synergy of Er3+-doped ZnO-CuO-ZnAl2O4 multi-phase
      oxides (Er3+-doped Zn/Cu/Al-MPO) via the formation of n-p-n double
      heterojunctions. The photocatalyst was prepared by synthesizing nanosheets of a
      Zn/Cu/Al/Er hydrotalcite-like compound (Zn/Cu/Al/Er-HLC) with a co-precipitation
      method followed by calcination of the nanosheets at 800  degrees C. The as
      prepared Er3+-doped Zn/Cu/Al-MPO inherits the nanosheet morphology of Zn/Cu/Al/Er
      HLC, and displays over-doubled photoactivity in the entire ultraviolet (UV),
      visible and NIR regions compared to undoped Zn/Cu/Al-MPO. The excellent
      photocatalytic activity of Er3+-doped Zn/Cu/Al-MPO, especially its strong NIR
      photoactivity, is ascribed to its Er3+-doped CuO-involved multi-crystalline phase
      heterostructure, i.e., n-p-n double heterojunctions, which does not only offer an
      enhanced NIR absorption but also promotes the separation of photogenerated charge
      carriers. Importantly, the synergy of all the parts of the n-p-n double
      heterojuctions plays an important role in interface band structure regulation for
      the enhancement of the photocatalytic properties of Er3+-doped Zn/Cu/Al-MPO. This
      work has demonstrated the feasibility of utilizing hydrotalcite-like precursors
      in the design of full-spectrum photocatalysts active in the NIR region.

PMID- 29181471
TI  - Versatile (eta6-arene)Ni(PCy3) nickel monophosphine precursors.
AB  - Nickel monophosphine arene adducts have been proposed as highly reactive
      intermediates capable of difficult C-O bond activation steps in Ni catalyzed
      cross-coupling reactions. The addition of N-methylmorpholine N-oxide to arene
      solutions of ([Cy3P)2Ni]2N2 allows for the synthesis of stable (eta6
      arene)Ni(PCy3) complexes. The isolation of these species demonstrates their
      viability as intermediates and provides an experimental means to test the
      hypothesized importance of the Ni(PCy3) moiety in bond activation and catalysis.

PMID- 29181470
TI  - Effect of benzocaine and propranolol on phospholipid-based bilayers.
AB  - Cell membranes play a fundamental role in protecting the cell from its
      surroundings, in addition to hosting many proteins with fundamental biological
      tasks. A study of drug/lipid interactions is a necessary and important step in
      fully clarifying the role and action mechanism of active ingredients, and
      shedding light on possible complications caused by drug overdosage. In this
      paper, the influence of benzocaine and propranolol drugs on the structure of l
      alpha-phosphatidylcholine-based membranes has been investigated by means of
      neutron reflectivity, grazing incidence small angle neutron scattering, and
      small/ultra-small angle neutron scattering. Investigations allowed discovering a
      stiffening of the membranes and the formation of stalks, caused by the presence
      of benzocaine. On the other hand, disordered bilayers (lamellar powders) and
      highly curved structures were found in the presence of propranolol. The results
      obtained may be rationalized in terms of the molecular structures of drugs and
      may serve as a starting point for explaining the toxic behavior in long-term and
      overdosage scenarios.

PMID- 29181472
TI  - Tailoring the dispersion of nanoparticles and the mechanical behavior of polymer
      nanocomposites by designing the chain architecture.
AB  - The structure-property relationship of polymer nanocomposites (PNCs) has been
      extensively investigated, but less effort has been devoted to studying the effect
      of chain architectures. Herein, through coarse-grained molecular dynamics
      simulation, we build six different chain architectures namely linear, branch-2
      (with two side chains), branch-4 (with four side chains), branch-10 (with ten
      side chains), star-4 (with four arms) and star-6 (with six arms), by fixing the
      molecular weight per chain. First, we examine the effect of the interfacial
      interaction between the polymer and nanoparticles (NPs) epsilonnp on the
      dispersion of NPs, by calculating the radial distribution function between NPs,
      the second virial coefficient and the average number of neighbor fillers. We
      observe a non-monotonic change of the NP dispersion as a function of epsilonnp
      for all PNCs with different chain architectures, indicating the optimal
      dispersion of NPs at moderate epsilonnp. Meanwhile, we find that the star-6,
      branch-4 and linear chains promote the best dispersion of NPs at moderate
      epsilonnp, compared to the other chain architectures. Then we investigate the
      strain hardening behavior and chain orientation of these PNCs under uniaxial
      tension. We find that the star-6 chains demonstrate relatively the most
      remarkable reinforced mechanical behavior of PNCs. Furthermore, we probe the
      effect of end-functionalization of polymer chains with different architectures on
      the dispersion of NPs, by comparing them to the case without any
      functionalization. We find that the introduction of the end-functionalization
      benefits mostly the high degree of chain branching for promoting the dispersion
      of NPs. Meanwhile, we observe that when the tensile strain is small, the branch-4
      structure shows relatively improved mechanical properties, however, when the
      tensile strain is large, the star-6 and branch-10 structures display the best
      mechanical properties, and the end-functionalization evidently improves the
      mechanical properties of the PNCs. Our simulation results provide guidelines to
      tailor the dispersion of NPs and the mechanical properties of PNCs, by taking
      advantage of the chain architecture and its end-functionalization strategy.

PMID- 29181473
TI  - Molecular dynamics simulations of propane in slit shaped silica nano-pores:
      direct comparison with quasielastic neutron scattering experiments.
AB  - Molecular motion under confinement has important implications for a variety of
      applications including gas recovery and catalysis. Propane confined in mesoporous
      silica aerogel as studied using quasielastic neutron scattering (QENS) showed
      anomalous pressure dependence in its diffusion coefficient (J. Phys. Chem. C,
      2015, 119, 18188). Molecular dynamics (MD) simulations are often employed to
      complement the information obtained from QENS experiments. Here, we report an MD
      simulation study to probe the anomalous pressure dependence of propane diffusion
      in silica aerogel. Comparison is attempted based on the self-diffusion
      coefficients and on the time scales of the decay of the simulated intermediate
      scattering functions. While the self-diffusion coefficients obtained from the
      simulated mean squared displacement profiles do not exhibit the anomalous
      pressure dependence observed in the experiments, the time scales of the decay of
      the intermediate scattering functions calculated from the simulation data match
      the corresponding quantities obtained in the QENS experiment and thus confirm the
      anomalous pressure dependence of the diffusion coefficient. The origin of the
      anomaly in pressure dependence lies in the presence of an adsorbed layer of
      propane molecules that seems to dominate the confined propane dynamics at low
      pressure, thereby lowering the diffusion coefficient. Further, time scales for
      rotational motion obtained from the simulations explain the absence of rotational
      contribution to the QENS spectra in the experiments. In particular, the
      rotational motion of the simulated propane molecules is found to exhibit large
      angular jumps at lower pressure. The present MD simulation work thus reveals
      important new insights into the origin of anomalous pressure dependence of
      propane diffusivity in silica mesopores and supplements the information obtained
      experimentally by QENS data.

PMID- 29181474
TI  - Monolithic capillary columns consisting of poly(glycidyl methacrylate-co-ethylene
      glycol dimethacrylate) and their diol derivatives with incorporated hydroxyl
      functionalized multiwalled carbon nanotubes for reversed-phase capillary
      electrochromatography.
AB  - Two types of monolithic stationary phases with incorporated hydroxyl
      functionalized multiwalled carbon nanotubes (OH-MWCNTs) were introduced and
      evaluated, namely, the poly(glycidyl methacrylate-co-ethylene glycol
      dimethacrylate) monolith, denoted as poly(GMA-co-EDMA), and a diol derivative of
      the poly(GMA-co-EDMA) monolith. The diol derivative monolith was obtained by
      subjecting the poly(GMA-co-EDMA) monolith with physically incorporated OH-MWCNTs
      to an acid treatment with 0.1 M sulfuric acid at a moderate temperature of 50 
      degrees C for a total of 7.5 h. Also, the poly(GMA-co-EDMA) monolith with both
      physically and covalently incorporated OH-MWCNTs was prepared by subjecting the
      physically incorporated monolithic column to a Lewis acid catalyzed reaction in
      the presence of BF3 in order to react some of the OH-MWCNTs with the epoxy rings
      of the poly(GMA-co-EDMA) monolith. In all cases, the OH-MWCNTs were subjected to
      high power sonication at an output power of 10 W for 15 min with the aim of
      better dispersing the incorporated nanotubes into the monoliths under
      investigation. In fact, high power sonication yielded columns with a relatively
      higher plate count (~2 fold increase) when compared to low power sonication.
      While the incorporation of OH-MWCNTs into the poly(GMA-co-EDMA) monolith acted as
      an amendment boosting the nonpolar character of the monolith and providing
      additional pi-pi interactions, the diol derivative monolith with its polar
      backbone character acted nearly as a support for the OH-MWCNT stationary phase
      giving rise to a carbon nanotube sorbent providing hydrophobic and pi-pi
      interactions via the incorporated OH-MWCNTs. These two kinds of columns were
      evaluated using alkylbenzenes, toluene derivatives, aniline compounds, phenols
      and polyaromatic hydrocarbons.

PMID- 29181475
TI  - Synthesis and chemical transformation of Ni nanoparticles embedded in silica.
AB  - Ni nanoparticles (NPs) catalyze many chemical reactions, in which they can become
      contaminated or agglomerate, resulting in poorer performance. We report
      deposition of silica (SiO2) onto Ni NPs from tetraethyl orthysilicate (TEOS)
      through a reverse microemulsion approach, which is accompanied by an unexpected
      etching process. Ni NPs with an average initial diameter of 27 nm were embedded
      in composite SiO2-overcoated Ni NPs (SiO2-Ni NPs) with an average diameter of 30
      nm. Each SiO2-Ni NP contained a ~7 nm oxidized Ni core and numerous smaller
      oxidized Ni NPs with diameters of ~2 nm distributed throughout the SiO2 shell.
      Etching of the Ni NPs is attributed to use of ammonium hydroxide as a catalyst
      for deposition of SiO2. Aliquots acquired during the deposition and etching
      process reveal agglomeration of SiO2 and Ni NPs, followed by dissociation into
      highly uniform SiO2-Ni NPs. This etching and embedding process may also be
      extended to other core materials. The stability of SiO2-Ni NPs was also
      investigated under high-temperature oxidizing and reducing environments. The
      structure of the SiO2-Ni NPs remained significantly unchanged after both
      oxidation and reduction, which suggests structural durability when used for
      catalysis.

PMID- 29181477
TI  - A facile synthesis of reduced holey graphene oxide for supercapacitors.
AB  - Hydroxyl radicals (OH) generated from a UV/O3 solution reaction is used to
      efficiently etch graphene oxide nanosheets under moderate conditions. Reduced
      holey graphene oxide is directly used as a supercapacitor electrode material and
      exhibits high specific capacitance (224 F g-1 at a current density of 1 A g-1)
      and high volumetric capacitance (up to 206 F cm-3).

PMID- 29181478
TI  - Synthesis of alpha-keto imides through copper-catalyzed oxidation of N-sulfonyl
      ynamides.
AB  - A novel copper-catalyzed N-oxide oxidation of N-sulfonyl ynamides is disclosed.
      This non-noble metal-catalyzed protocol enables facile and efficient access to
      valuable alpha-keto imides in generally good to excellent yields. Other notable
      features of this method include widespread availability of the substrates,
      compatibility with broad functional groups, a simple procedure, mild conditions,
      and in particular, no need to exclude moisture or air ("open flask").

PMID- 29181479
TI  - Ruthenium complex-modified carbon nanodots for lysosome-targeted one- and two
      photon imaging and photodynamic therapy.
AB  - Nanohybrids can in most cases kill cancer cells more efficiently as compared with
      free photosensitizers. In this work, we constructed nanohybrid Ru1@CDs composed
      of carbon nanodots (CDs) and a phosphorescent Ru(ii) complex (Ru1) for one- and
      two-photon photodynamic therapy of cancer. The photosensitizer and imaging agent
      Ru1 is decorated onto the nanocarrier CDs covalently. Ru1 and Ru1@CDs can
      penetrate into cancer cells through an energy-dependent mechanism and
      endocytosis, respectively. Both Ru1 and Ru1@CDs are capable of lysosome-targeted
      phosphorescence imaging and photodamage under either 450 nm (one-photon) or 810
      nm (two-photon) excitation. Conjugation with CDs can increase the cellular uptake
      efficacy of Ru1. Mechanism investigations show that both Ru1 and Ru1@CDs can
      induce apoptosis through generation of reactive oxygen species and cathepsin
      initiated apoptotic signaling pathways. Upon two-photon excitation, Ru1@CDs show
      better penetrability, as well as higher inhibitory effects on cancer cell growth
      in both 2D cell and 3D multicellular tumor spheroid models. Our work provides an
      effective strategy for the construction of multifunctional imaging and
      phototherapeutic nanohybrids for the treatment of cancer.

PMID- 29181480
TI  - Clarifying the dehydrogenation pathway of catalysed Li4(NH2)3BH4-LiH composites.
AB  - The effect of different metal oxides (Co3O4 and NiO) on the dehydrogenation
      reaction pathways of the Li4(NH2)3BH4-LiH composite was investigated. The
      additives were reduced to metallic species i.e. Co and Ni which act as catalysts
      by breaking the B-H bonds in the Li-B-N-H compounds. The onset decomposition
      temperature was lowered by 32  degrees C for the Ni-catalysed sample, which
      released 8.8 wt% hydrogen below 275  degrees C. It was demonstrated that the
      decomposition of the doped composite followed a mechanism via LiNH2 and Li3BN2
      formation as the end product with a strong reduction of NH3 emission. The sample
      could be partially re-hydrogenated (~1.5 wt%) due to lithium imide/amide
      transformation. To understand the role of LiH, Li4(NH2)3BH4-LiH-NiO and
      Li4(NH2)3BH4-NiO composites were compared. The absence of LiH as a reactant
      forced the system to follow another path, which involved the formation of an
      intermediate phase of composition Li3BN2H2 at the early stages of dehydrogenation
      and the end products LiNH2 and monoclinic Li3BN2. We provided evidence for the
      interaction between NiO and LiNH2 during heating and proposed that the presence
      of Li facilitates a NHx-rich environment and the Ni catalyst mediates the
      electron transfer to promote NHx coupling.

PMID- 29181481
TI  - A graphene-like membrane with an ultrahigh water flux for desalination.
AB  - An ultrathin nanoporous membrane which combines high water permeability and high
      salt rejection is the core of ultrafiltration technology. Recently, we reported
      the synthesis of a chemically robust and nanoporous two-dimensional conjugated
      aromatic polymer (2D-CAP) membrane. Due to its array of highly regular sub
      nanometer pores and channels, the ultrathin 2D-CAP membrane can be potentially
      used in desalination. Herein, we used molecular dynamics simulations to analyze
      the transmembrane hydrodynamics of mono- and multi-layer 2D-CAP membranes as a
      function of layer number. The energy barriers to water and ions across these
      membranes were calculated to evaluate the potential of 2D-CAP to function as the
      ultimate RO membrane. Our simulation results show that the bilayer CAP membrane
      exhibits superior ion rejection (100%) and a water flux (1172 L m-2 h-1 bar-1)
      with a performance that is three orders of magnitude higher than the commercial
      reverse osmosis membrane, which is three times higher than the theoretically
      reported monolayer nanoporous MoS2 membrane (the state-of-the-art membrane
      reported for desalination). In addition, the 2D-CAP bilayer membrane is highly
      resistant to swelling even at a high water flux. The monolayer 2D-CAP membrane
      shows good ion selectivity between monovalent and divalent ions.

PMID- 29181483
TI  - Continuing Progress in Alzheimer's Disease Trials: Cause for Optimism.

PMID- 29181485
TI  - Prospects for Effective Treatment of the Dementia-Alzheimer Syndrome: A Renewed
      Odyssey in Search of the Magic Elixir.

PMID- 29181484
TI  - Recruitment of At-Risk Participants for Clinical Trials: A Major Paradigm Shift
      for Alzheimer's Disease Prevention.

PMID- 29181486
TI  - Epigallocatechin 3-Gallate as an Inhibitor of Tau Phosphorylation and
      Aggregation: A Molecular and Structural Insight.
AB  - Polyphenols such as Epigallocatechin-3 gallate (EGCG) are currently bearer of
      hope to prevent or at least to slow down the deleterious effect of Tauopathies
      such as Alzheimer disease. One of the main effects of these neurodegenerative
      pathologies is the hyperphosphorylation and consequent aggregation of the Tau
      protein that leads to the irremediable neuronal cells death. In the present
      paper, we show how EGCG can play a crucial role to prevent Tau aggregation: (i)
      in binding Tau in its phosphorylation region with an affinity of the same order
      of magnitude than kinases (0.5 mM), hindering their access to the protein and
      (ii) in modifying the 3D-structure of Tau whose preferential conformation changes
      in the presence of EGCG. For this purpose, two peptides were synthesized, one of
      20 residues long issued from the first Proline-rich region of Tau (171Ile
      190Lys), the second of 50 residues long (171Ile-220Thr) corresponding to more
      than 50% of the Tau Proline rich domaine. The total attribution of all the 1H,
      13C and 15N resonances of the two peptides has been achieved thanks to a "divide
      and conquer" strategy leading to their 3D structure preference and their affinity
      towards EGCG.

PMID- 29181488
TI  - Preclinical and Clinical Development of ABBV-8E12, a Humanized Anti-Tau Antibody,
      for Treatment of Alzheimer's Disease and Other Tauopathies.
AB  - Tau neurofibrillary tangles are found in the brains of patients suffering from
      Alzheimer's disease and other tauopathies. The progressive spreading of tau
      pathology from one brain region to the next is believed to be caused by
      extracellular transsynaptic transmission of misfolded tau between neurons.
      Preclinical studies have shown that antibodies against tau can prevent this
      transfer of misfolded tau between cells. Thus, antibodies against tau have the
      potential to stop or slow the progression of tau pathology observed in human
      tauopathies. To test this hypothesis, a humanized anti-tau antibody (ABBV-8E12)
      was developed and a phase 1 clinical trial of this antibody has been completed.
      The double-blind, placebo-controlled phase 1 study tested single doses of ABBV
      8E12 ranging from 2.5 to 50 mg/kg in 30 patients with progressive supranuclear
      palsy (PSP). ABBV-8E12 was found to have an acceptable safety profile with no
      clinically concerning trends in the number or severity of adverse events between
      the placebo and dosed groups. Pharmacokinetic modelling showed that the antibody
      has a plasma half-life and cerebrospinal fluid:plasma ratio consistent with other
      humanized antibodies, and there were no signs of immunogenicity against ABBV
      8E12. Based on the acceptable safety and tolerability profile of single doses of
      ABBV-8E12, AbbVie is currently enrolling patients into two phase 2 clinical
      trials to assess efficacy and safety of multiple doses of ABBV-8E12 in patients
      with early Alzheimer's disease or PSP.

PMID- 29181487
TI  - Vitamin E Supplementation Reduces Cellular Loss in the Brain of a Premature Aging
      Mouse Model.
AB  - BACKGROUND: Aging is a highly complex biological process driven by multiple
      factors. Its progression can partially be influenced by nutritional
      interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as
      nutritional supplement for its ability to prevent or delay the onset of specific
      aging pathologies, including neurodegenerative disorders. PURPOSE: We aimed here
      to investigate the effect of vitamin E during aging progression in a well
      characterized mouse model for premature aging. METHOD: Xpg-/- animals received
      diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed)
      vitamin E concentration and their phenotype was monitored during aging
      progression. Vitamin E content was analyzed in the feed, for stability reasons,
      and in mouse plasma, brain, and liver, for effectiveness of the treatment.
      Subsequent age-related changes were monitored for improvement by increased
      vitamin E or worsening by depletion in both liver and nervous system, organs
      sensitive to oxidative stress. RESULTS: Mice supplemented with high levels of
      vitamin E showed a delayed onset of age-related body weight decline and
      appearance of tremors when compared to mice with a low dietary vitamin E intake.
      DNA damage resulting in liver abnormalities such as changes in polyploidy, was
      considerably prevented by elevated amounts of vitamin E. Additionally,
      immunohistochemical analyses revealed that high intake of vitamin E, when
      compared with low and medium levels of vitamin E in the diet, reduces the number
      of p53-positive cells throughout the brain, indicative of a lower number of cells
      dying due to DNA damage accumulated over time. CONCLUSIONS: Our data underline a
      neuroprotective role of vitamin E in the premature aging animal model used in
      this study, likely via a reduction of oxidative stress, and implies the
      importance of improved nutrition to sustain health.

PMID- 29181489
TI  - The Alzheimer's Prevention Initiative Generation Program: Evaluating CNP520
      Efficacy in the Prevention of Alzheimer's Disease.
AB  - Alzheimer's disease pathology begins decades before the onset of clinical
      symptoms. This provides an opportunity for interventional clinical trials to
      potentially delay or prevent the onset of cognitive impairment or dementia.
      CNP520 (a beta-site-amyloid precursor protein-cleaving enzyme inhibitor) is in
      clinical development for the treatment of preclinical Alzheimer's disease under
      the Alzheimer's Prevention Initiative Generation Program. The Alzheimer's
      Prevention Initiative is a public-private partnership intended to accelerate the
      evaluation of Alzheimer's disease prevention therapies. The Generation Program
      comprises two pivotal phase II/III studies with similar designs to assess the
      efficacy and safety of investigational treatments in a cognitively unimpaired
      population at increased risk for developing Alzheimer's disease based on age and
      apolipoprotein E (APOE) genotype (i.e., presence of the APOE epsilon4 allele).
      The program has been designed to maximize benefit to Alzheimer's disease
      research. Generation Study 1 (NCT02565511) and Generation Study 2 (NCT03131453)
      are currently enrolling; their key features are presented here.

PMID- 29181490
TI  - Development Review of the BACE1 Inhibitor Lanabecestat (AZD3293/LY3314814).
AB  - Several ongoing clinical development programs are investigating potential disease
      modifying treatments for Alzheimer's disease (AD), including lanabecestat
      (AZD3293/LY3314814). Lanabecestat is a brain-permeable oral inhibitor of human
      beta-site amyloid (Abeta) precursor protein-cleaving enzyme 1 (BACE1) that
      reduces Abeta production. As a potent BACE1 inhibitor, lanabecestat significantly
      reduced soluble Abeta species and soluble amyloid precursor proteins (sAPPbeta)
      in mouse, guinea pig, and dog in a time- and dose-dependent manner. Significant
      reductions in plasma and cerebrospinal fluid (CSF) Abeta1-40 and Abeta1-42 were
      observed in Phase 1 studies of healthy subjects and AD patients treated with
      lanabecestat. Three lanabecestat trials are ongoing and intended to support
      registration in Early AD: (1) Phase 2/3 study in patients with mild cognitive
      impairment (MCI) due to AD and mild AD dementia (AMARANTH, NCT02245737); (2)
      Delayed-start extension study (AMARANTH-EXTENSION, NCT02972658) for patients who
      have completed treatment in the AMARANTH Study; and (3) Phase 3 study in mild AD
      dementia (DAYBREAK-ALZ, NCT02783573). This review will discuss the development of
      lanabecestat, results from the completed nonclinical and clinical studies, as
      well as describe the ongoing Phase 3 clinical trials.

PMID- 29181491
TI  - Clinical Development of Aducanumab, an Anti-Abeta Human Monoclonal Antibody Being
      Investigated for the Treatment of Early Alzheimer's Disease.
AB  - The amyloid hypothesis has been the dominant framework for Alzheimer's disease
      (AD) research, including the development of anti-AD therapies. However, none of
      the phase III clinical trials conducted to date that targeted amyloid beta
      (Abeta) production, aggregation, or clearance demonstrated a statistically
      significant treatment effect in patients with AD. This includes the approach of
      using monoclonal antibodies that recognize various Abeta epitopes and display
      different binding selectivity. While some monoclonal antibodies have failed in
      phase III trials, several are still in development. Aducanumab (BIIB037) is a
      human antibody that selectively targets aggregated forms of Abeta, including
      soluble oligomers and insoluble fibrils. In PRIME (NCT01677572), an ongoing phase
      Ib trial (N=196 patients dosed), aducanumab was shown to reduce Abeta plaques and
      slow decline in clinical measures in patients with prodromal or mild AD, with
      acceptable safety and tolerability. The main safety finding was amyloid-related
      imaging abnormalities (ARIA), a side effect associated with removal of Abeta,
      which was dose-dependent and occurred more often in ApoE epsilon4 carriers than
      non-carriers. ENGAGE (NCT02477800) and EMERGE (NCT02484547), the ongoing phase
      III trials of aducanumab in early AD, have been designed based on the outcomes of
      PRIME and on lessons from past clinical trials in patients with AD. Those study
      design features include patient selection with confirmed Abeta pathology,
      ensuring sufficient target engagement, and conducting clinical trials in patients
      at earlier symptomatic stages of AD.

PMID- 29181492
TI  - Developing Disease-Modifying Treatments in Alzheimer's Disease - A Perspective
      from Roche and Genentech.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disease for which no
      preventative or disease-modifying treatments currently exist. Pathological
      hallmarks include amyloid plaques and neurofibrillary tangles composed of hyper
      phosphorylated tau protein. Evidence suggests that both pathologies are self
      propagating once established. However, the lag time between neuropathological
      changes in the brain and the onset of even subtle clinical symptomatology means
      that patients are often diagnosed late when pathology, and neurodegeneration
      secondary to these changes, may have been established for several years. Complex
      pathological pathways associated with susceptibility to AD and changes that occur
      downstream of the neuropathologic process further contribute to the challenging
      endeavour of developing novel disease-modifying therapy. Recognising this
      complexity, effective management of AD must include reliable screening and early
      diagnosis in combination with effective therapeutic management of the
      pathological processes. Roche and Genentech are committed to addressing these
      unmet needs through developing a comprehensive portfolio of diagnostics and novel
      therapies. Beginning with the most scientifically supported targets, this
      approach includes two targeted amyloid-beta monoclonal antibody therapies,
      crenezumab and gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as
      well as a robust biomarker platform to aid in the early identification of people
      at risk or in the early stages of AD. Identification and implementation of
      diagnostic tools will support the enrolment of patients into clinical trials;
      furthermore, these tools should also support evaluation of the clinical efficacy
      and safety profile of the novel therapeutic agents tested in these trials. This
      review discusses the therapeutic agents currently under clinical development.

PMID- 29181493
TI  - Neflamapimod: Clinical Phase 2b-Ready Oral Small Molecule Inhibitor of p38alpha
      to Reverse Synaptic Dysfunction in Early Alzheimer's Disease.
AB  - Neflamapimod (previously code named VX-745) is a clinical phase 2b-ready highly
      specific inhibitor of the intra-cellular enzyme p38 mitogen activated protein
      kinase alpha ("p38alpha") that is being developed as a disease-modifying drug for
      Alzheimer's disease (AD) that acts via targeting synaptic dysfunction.
      Neflamapimod was discovered through a proprietary structure-based drug discovery
      platform at Vertex Pharmaceuticals, and developed previously by Vertex through to
      phase 2a in rheumatoid arthritis. EIP Pharma licensed the compound in 2014 for
      development and commercialization as a treatment of central nervous system (CNS)
      disorders. Neflamapimod is the most advanced in the clinic drug that targets
      specific molecular mechanisms within neurons that leads to synaptic dysfunction,
      the pathogenic process that is now considered to be a major driver of the
      development of memory deficits and disease progression in the early stages of AD.
      Based on the scientific rationale of targeting synaptic dysfunction and the
      preclinical data, neflamapimod has the potential to both reverse memory deficits
      and slow disease progression. Phase 2a clinical data in patients with early-stage
      AD (MMSE 20-28, biomarker positive) provides evidence that the preclinical
      science may be translatable to human Alzheimer's, as 6- to 12-weeks of
      neflamapimod treatment led to significant improvement in episodic memory, the
      best clinical measure of synaptic dysfunction in AD. A phase 2b six-month placebo
      controlled 150-patient clinical study is anticipated to start by end of 2017.
      This study is designed to definitively demonstrate that neflamapimod reverses
      memory deficits, and also to provide preliminary evidence that the drug slows
      disease progression.

PMID- 29181494
TI  - Wide Complex Tachycardia in a Patient Without Conduction System Disease.

PMID- 29181495
TI  - Quality Improvement for Quality Improvement Studies.

PMID- 29181496
TI  - The Evidence Basis for the American College of Rheumatology Practice Guidelines.

PMID- 29181497
TI  - Will You Be My Mentor?-Four Archetypes to Help Mentees Succeed in Academic
      Medicine.

PMID- 29181498
TI  - Traumatic Brain Injury and Cases of Abnormal Menstrual Pattern.

PMID- 29181499
TI  - Association Between Neonatal Intensive Care Unit Admission Rates and Illness
      Acuity.
AB  - Importance: Most neonates admitted to a neonatal intensive care unit (NICU) are
      born at gestational age (GA) of 34 weeks or more. The degree of uniformity of
      admission criteria for these infants is unclear, particularly at the low-acuity
      end of the range of conditions warranting admission. Objectives: To describe
      variation in NICU admission rates for neonates born at GA of 34 weeks or more and
      examine whether such variation is associated with high illness acuity or
      designated facility level of care. Design, Setting, and Participants: Cross
      sectional study of 35 921 NICU inborn admissions of GA at 34 weeks or more during
      calendar year 2015, using a population database of inborn NICU admissions at 130
      of the 149 hospitals in California with a NICU. The aggregate service population
      comprised 358 453 live births. The individual NICU was the unit of observation
      and analysis. The analysis was stratified by designated facility level of care
      and correlations with the percentage admissions with high illness acuity were
      explored. The hypothesis at the outset of the study was that inborn admission
      rates would correlate positively with the percentage of admissions with high
      illness acuity. Exposures: Live birth at GA of 34 weeks or more. Main Outcomes
      and Measures: Inborn NICU admission rate. Results: Of the total of 358 453 live
      births at GA of 34 weeks or more, 35 921 infants were admitted to a NICU and
      accounted for 79.2% of all inborn NICU admissions; 4260 (11.9%) of these
      admissions met high illness acuity criteria. Inborn admission rates varied 34
      fold, from 1.1% to 37.7% of births (median, 9.7%; mean [SD], 10.6% [5.8%]).
      Percentage with high illness acuity varied 40-fold, from 2.4% to 95% (median,
      11.3%; mean, 13.2% [9.9%]). Inborn admission rate correlated inversely with
      percentage of admissions with high illness acuity (Spearman rho = -0.3034, P <
      .001). Among regional NICUs capable of caring for patients with the highest
      degree of illness and support needs, inborn admission rate did not significantly
      correlate with percentage of admissions with high illness acuity (Spearman rho = 
      0.21, P = .41). Conclusions and Relevance: Percentage of admissions with high
      illness acuity does not explain 34-fold variation in NICU inborn admission rates
      for neonates born at GA of 34 weeks or more. The findings are consistent with a
      supply-sensitive care component and invite future investigation to clarify the
      lower-acuity end of the range of conditions considered to warrant neonatal
      intensive care.

PMID- 29181500
TI  - Perinatal Diagnosis, Management, and Follow-up of Cystic Renal Diseases: A
      Clinical Practice Recommendation With Systematic Literature Reviews.
AB  - Importance: Prenatal and neonatal cystic kidney diseases are a group of rare
      disorders manifesting as single, multiple unilateral, or bilateral cysts or with
      increased echogenicity of the renal cortex without macroscopic cysts. They may be
      accompanied by grossly enlarged kidneys, renal oligohydramnios, pulmonary
      hypoplasia, extrarenal abnormalities, and neonatal kidney failure. The prognosis
      is extremely variable from trivial to very severe or even uniformly fatal, which
      poses significant challenges to prenatal counseling and management. Objective: To
      provide a clinical practice recommendation for fetal medicine specialists,
      obstetricians, neonatologists, pediatric nephrologists, pediatricians, and human
      geneticists by aggregating current evidence and consensus expert opinion on
      current management of cystic nephropathies before and after birth. Methods: After
      8 systematic literature reviews on clinically relevant questions were prepared
      (including 90 studies up to mid-2016), recommendations were formulated and
      formally graded at a consensus meeting that included experts from all relevant
      specialties. After further discussion, the final version was voted on by all
      members using the Delphi method. The recommendations were reviewed and endorsed
      by the working groups on inherited renal disorders of the European Renal
      Association-European Dialysis and Transplant Association (ERA-EDTA) and European
      Society for Paediatric Nephrology (ESPN); the German Society of Obstetrics and
      Gynecology (DGGG), German Society of Perinatal Medicine (DGPM), and German
      Society of Ultrasound in Medicine (DEGUM); and the alliance of patient
      organizations, PKD International. Recommendations: The group makes a number of
      recommendations on prenatal and postnatal imaging by ultrasound and magnetic
      resonance imaging, genetic testing, prenatal counseling, in utero therapeutic
      interventions, and postnatal management of prenatal and neonatal cystic kidney
      diseases, including provision of renal replacement therapy in neonates. In
      addition to detailed knowledge about possible etiologies and their prognosis,
      physicians need to be aware of recent improvements and remaining challenges of
      childhood chronic kidney disease, neonatal renal replacement therapy, and
      intensive pulmonary care to manage these cases and to empower parents for
      informed decision making.

PMID- 29181501
TI  - Rapidly Changing Skin Lesion in a Teenage Boy.

PMID- 29181502
TI  - Traumatic Brain Injury and Cases of Abnormal Menstrual Pattern-Reply.

PMID- 29181503
TI  - Anticipatory smooth pursuit eye movements evoked by probabilistic cues.
AB  - Anticipatory smooth eye movements (ASEM; smooth eye movements in the direction of
      anticipated target motion) are elicited by cues that signal the direction of
      future target motion with high levels of certainty. Natural cues, however, rarely
      convey information with perfect certainty, and responses to uncertainty provide
      insights about how predictive behaviors are generated. Subjects smoothly pursued
      targets that moved to the right or left with varying cued probabilities. ASEM
      strength in a given direction increased with the probability level. The type of
      cue also played a role. ASEM elicited by symbolic visual cues tended to
      underweight low probabilities and overweight high probabilities. Cues based on
      memory (varying the proportion of trials with left or right motion) produced the
      opposite pattern, overweighting low probabilities and underweighting high
      probabilities. Finally, cues whose perceptual structure depicted the motion path
      produced a bias in ASEM in the depicted direction that was maintained across
      levels of cue congruency. The results show that the smooth pursuit system relies
      on a combination of signals, including memory for recent target motions,
      interpretation of cues, and prior beliefs about the relationship between the
      perceptual configuration and the motion path to determine the anticipatory
      response in the presence of uncertainty.

PMID- 29181504
TI  - Patient-Sharing Networks of Physicians and Health Care Utilization and Spending
      Among Medicare Beneficiaries.
AB  - Importance: Physicians are embedded in informal networks in which they share
      patients, information, and behaviors. Objective: We examined the association
      between physician network properties and health care spending, utilization, and
      quality of care among Medicare beneficiaries. Design, Setting, and Participants:
      In this cross-sectional study, we applied methods from social network analysis to
      Medicare administrative data from 2006 to 2010 for an average of 3 761 223
      Medicare beneficiaries per year seen by 40 241 physicians practicing in 51
      hospital referral regions (HRRs) to identify networks of physicians linked by
      shared patients. We improved on prior methods by restricting links to physicians
      who shared patients for distinct episodes of care, thereby excluding potentially
      spurious linkages between physicians treating common patients but for unrelated
      reasons. We also identified naturally occurring communities of more tightly
      linked physicians in each region. We examined the relationship between network
      properties measured in the prior year and outcomes in the subsequent year using
      regression models. Main Outcomes and Measures: Spending on total medical
      services, hospital, physician, and other services, use of services, and quality
      of care. Results: The mean patient age across the 5 years of study was 72.3 years
      and 58.5% of the participants were women. The mean age across communities of
      included physicians was 49 years and approximately 78% were men. Mean total
      annual spending per patient was $10 051. Total spending was higher for patients
      of physicians with more connections to other physicians ($1009 for a 1-standard
      deviation increase, P < .001) and more shared care outside of their community
      ($172, P < .001). Spending on inpatient care was slightly lower for patients of
      physicians whose communities had higher proportions of primary care physicians (
      $38, P < .001). Patients cared for by physicians linked to more physicians also
      had more hospital admissions and days (0.02 and 0.18, respectively; both P < .001
      for a 1-standard deviation increase in the number of connected physicians), more
      emergency visits (0.02, P < .001), more visits to specialists (0.37, P < .001),
      and more primary care visits (0.11, P < .001). Patients whose physicians'
      networks had more primary care physicians had more primary care visits (0.44, P <
      .001) and fewer specialist and emergency visits (-0.33 [P < .001] and -0.008 [P =
      .008], respectively). The various measures of quality were inconsistently related
      to the network measures. Conclusions and Relevance: Characteristics of
      physicians' networks and the position of physicians in the network were
      associated with overall spending and utilization of services for Medicare
      beneficiaries.

PMID- 29181505
TI  - Rethinking Eligibility for Experimental Clinical Trials.

PMID- 29181506
TI  - Sensitivity to the Deficits Associated With Traumatic Brain Injury or Chronic
      Traumatic Encephalopathy.

PMID- 29181507
TI  - Mentoring of Early-Stage Investigators When Funding Is Tight: The Childhood
      Obesity Prevention and Treatment Research Experience.

PMID- 29181508
TI  - Cervical Cancer Screening: The Transformational Role of Routine Human
      Papillomavirus Testing.

PMID- 29181509
TI  - Effect of Several Negative Rounds of Human Papillomavirus and Cytology Co-testing
      on Safety Against Cervical Cancer: An Observational Cohort Study.
AB  - Background: Current U.S. cervical cancer screening and management guidelines do
      not consider previous screening history, because data on multiple-round human
      papillomavirus (HPV) and cytology "co-testing" have been unavailable. Objective:
      To measure cervical cancer risk in routine practice after successive negative
      screening co-tests at 3-year intervals. Design: Observational cohort study.
      Setting: Integrated health care system (Kaiser Permanente Northern California,
      Oakland, California). Patients: 990 013 women who had 1 or more co-tests from
      2003 to 2014. Measurements: 3- and 5-year cumulative detection of (risk for)
      cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, and cervical
      cancer (>=CIN3) in women with different numbers of negative co-tests, overall and
      within subgroups defined by previous co-test results or baseline age. Results:
      Five-year >=CIN3 risks decreased after each successive negative co-test screening
      round (0.098%, 0.052%, and 0.035%). Five-year >=CIN3 risks for an HPV-negative co
      test, regardless of the cytology result, nearly matched the performance
      (reassurance) of a negative co-test for each successive round of screening
      (0.114%, 0.061%, and 0.041%). By comparison, >=CIN3 risks for the cytology
      negative co-test, regardless of the HPV result, also decreased with each
      successive round, but 3-year risks were as high as 5-year risks after an HPV
      negative co-test (0.199%, 0.065%, and 0.043%). No interval cervical cancer cases
      were diagnosed after the second negative co-test. Independently, >=CIN3 risks
      decreased with age. Length of previous screening interval did not influence
      future >=CIN3 risks. Limitation: Interval-censored observational data.
      Conclusion: After 1 or more negative cervical co-tests (or HPV tests), longer
      screening intervals (every 5 years or more) might be feasible and safe. Primary
      Funding Source: National Cancer Institute Intramural Research Program.

PMID- 29181511
TI  - The Value-Based Payment Modifier: Program Outcomes and Implications for
      Disparities.
AB  - Background: When risk adjustment is inadequate and incentives are weak, pay-for
      performance programs, such as the Value-Based Payment Modifier (Value Modifier
      [VM]) implemented by the Centers for Medicare & Medicaid Services, may contribute
      to health care disparities without improving performance on average. Objective:
      To estimate the association between VM exposure and performance on quality and
      spending measures and to assess the effects of adjusting for additional patient
      characteristics on performance differences between practices serving higher-risk
      and those serving lower-risk patients. Design: Exploiting the phase-in of the VM
      on the basis of practice size, regression discontinuity analysis and 2014
      Medicare claims were used to estimate differences in practice performance
      associated with exposure of practices with 100 or more clinicians to full VM
      incentives (bonuses and penalties) and exposure of practices with 10 or more
      clinicians to partial incentives (bonuses only). Analyses were repeated with 2015
      claims to estimate performance differences associated with a second year of
      exposure above the threshold of 100 or more clinicians. Performance differences
      were assessed between practices serving higher- and those serving lower-risk
      patients after standard Medicare adjustments versus adjustment for additional
      patient characteristics. Setting: Fee-for-service Medicare. Patients: Random 20%
      sample of beneficiaries. Measurements: Hospitalization for ambulatory care
      sensitive conditions, all-cause 30-day readmissions, Medicare spending, and
      mortality. Results: No statistically significant discontinuities were found at
      the threshold of 10 or more or 100 or more clinicians in the relationship between
      practice size and performance on quality or spending measures in either year.
      Adjustment for additional patient characteristics narrowed performance
      differences by 9.2% to 67.9% between practices in the highest and those in the
      lowest quartile of Medicaid patients and Hierarchical Condition Category scores.
      Limitation: Observational design and administrative data. Conclusion: The VM was
      not associated with differences in performance on program measures. Performance
      differences between practices serving higher- and those serving lower-risk
      patients were affected considerably by additional adjustments, suggesting a
      potential for Medicare's pay-for-performance programs to exacerbate health care
      disparities. Primary Funding Source: The Laura and John Arnold Foundation and
      National Institute on Aging.

PMID- 29181510
TI  - Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children
      and Young Adults.
AB  - Importance: Neurologic disorders with isolated symptoms or complex syndromes are
      relatively frequent among mitochondrial inherited diseases. Recessive RTN4IP1
      gene mutations have been shown to cause isolated and syndromic optic
      neuropathies. Objective: To define the spectrum of clinical phenotypes associated
      with mutations in RTN4IP1 encoding a mitochondrial quinone oxidoreductase.
      Design, Setting, and Participants: This study involved 12 individuals from 11
      families with severe central nervous system diseases and optic atrophy. Targeted
      and whole-exome sequencing were performed-at Hospital Angers (France), Institute
      of Neurology Milan (Italy), Imagine Institute Paris (France), Helmoltz Zentrum of
      Munich (Germany), and Beijing Genomics Institute (China)-to clarify the molecular
      diagnosis of patients. Each patient's neurologic, ophthalmologic, magnetic
      resonance imaging, and biochemical features were investigated. This study was
      conducted from May 1, 2014, to June 30, 2016. Main Outcomes and Measures:
      Recessive mutations in RTN4IP1 were identified. Clinical presentations ranged
      from isolated optic atrophy to severe encephalopathies. Results: Of the 12
      individuals in the study, 6 (50%) were male and 6 (50%) were female. They ranged
      in age from 5 months to 32 years. Of the 11 families, 6 (5 of whom were
      consanguineous) had a member or members who presented isolated optic atrophy with
      the already reported p.Arg103His or the novel p.Ile362Phe, p.Met43Ile, and
      p.Tyr51Cys amino acid changes. The 5 other families had a member or members who
      presented severe neurologic syndromes with a common core of symptoms, including
      optic atrophy, seizure, intellectual disability, growth retardation, and elevated
      lactate levels. Additional clinical features of those affected were deafness,
      abnormalities on magnetic resonance images of the brain, stridor, and abnormal
      electroencephalographic patterns, all of which eventually led to death before age
      3 years. In these patients, novel and very rare homozygous and compound
      heterozygous mutations were identified that led to the absence of the protein and
      complex I disassembly as well as mild mitochondrial network fragmentation.
      Conclusions and Relevance: A broad clinical spectrum of neurologic features,
      ranging from isolated optic atrophy to severe early-onset encephalopathies, is
      associated with RTN4IP1 biallelic mutations and should prompt RTN4IP1 screening
      in both syndromic neurologic presentations and nonsyndromic recessive optic
      neuropathies.

PMID- 29181512
TI  - Consumer Behaviors Among Individuals Enrolled in High-Deductible Health Plans in
      the United States.

PMID- 29181513
TI  - Sensitivity to the Deficits Associated With Traumatic Brain Injury or Chronic
      Traumatic Encephalopathy-Reply.

PMID- 29181515
TI  - Landmark Article Transforms Traditional View of the Autonomic Nervous System.

PMID- 29181514
TI  - Comparative Analysis of Biopsy Upgrading in Four Prostate Cancer Active
      Surveillance Cohorts.
AB  - Background: Active surveillance (AS) is increasingly accepted for managing low
      risk prostate cancer, yet there is no consensus about implementation. This lack
      of consensus is due in part to uncertainty about risks for disease progression,
      which have not been systematically compared or integrated across AS studies with
      variable surveillance protocols and dropout to active treatment. Objective: To
      compare risks for upgrading from a Gleason score (GS) of 6 or less to 7 or more
      across AS studies after accounting for differences in surveillance intervals and
      competing treatments and to evaluate tradeoffs of more versus less frequent
      biopsies. Design: Joint statistical model of longitudinal prostate-specific
      antigen (PSA) levels and risks for biopsy upgrading. Setting: Johns Hopkins
      University (JHU); Canary Prostate Active Surveillance Study (PASS); University of
      California, San Francisco (UCSF); and University of Toronto (UT) AS studies.
      Patients: 2576 men aged 40 to 80 years with a GS between 2 and 6 and clinical
      stage T1 or T2 prostate cancer enrolled between 1995 and 2014. Measurements: PSA
      levels and biopsy GSs. Results: After variable surveillance intervals and
      competing treatments were accounted for, estimated risks for biopsy upgrading
      were similar in the PASS and UT studies but higher in UCSF and lower in JHU
      studies. All cohorts had a delay of 3 to 5 months in detecting upgrading with
      biennial biopsies starting after a first confirmatory biopsy versus annual
      biopsies. Limitation: The model does not account for possible misclassification
      of biopsy GS. Conclusion: Men in different AS studies have different risks for
      biopsy upgrading after variable surveillance protocols and competing treatments
      are accounted for. Despite these differences, the consequences of more versus
      less frequent biopsies seem to be similar across cohorts. Biennial biopsies seem
      to be an acceptable alternative to annual biopsies. Primary Funding Source:
      National Cancer Institute.

PMID- 29181516
TI  - Measuring Adherence and Outcomes in the Treatment of Patients With Multiple
      Sclerosis.
AB  - Context: Both adherence and outcomes are more difficult to measure in patients
      with multiple sclerosis (MS) than in patients with diseases such as hypertension,
      for which most medications are taken orally and surrogate outcomes (eg, blood
      pressure) are routinely collected. Objectives: To characterize the adherence and
      outcomes of patients with MS within a large integrated health system and to
      assess the relationship between adherence and outcomes. Study Design:
      Retrospective review of adherence and health care utilization outcomes via
      electronic health records and claims (2004-2013) combined with a prospective
      survey regarding adherence and functional outcomes (2012-2013). Methods:
      Retrospectively, medication possession ratios were calculated, and adherence
      groups were compared regarding health care utilization and costs. Prospectively,
      patients were recruited to complete questionnaires to measure self-reported
      adherence (SRA) and MS-specific outcomes, including the Multiple Sclerosis Impact
      Scale (MSIS), the Kurtzke Expanded Disability Status Scale (EDSS), and the
      Treatment Satisfaction Questionnaire for Medication (TSQM). Regression was used
      to statistically test for differences in these outcomes among adherence groups.
      Results: A total of 681 patients were studied. Most patients (307 of 375 [82%] in
      the retrospective cohort and 244 of 306 [89%] in the prospective cohort) had
      greater that 80% adherence to their MS medications. Mean inpatient days per
      patient for MS-related admissions was highest for high-adherence than for
      intermediate and low-adherence patients (0.52 vs 0.23 and 0.34, respectively;
      P<.001), but no other associations between adherence and health care utilization
      were found. Mean outpatient costs and total costs were lowest for the low
      adherence group, suggesting that higher adherence may not guarantee cost savings
      overall. Patients with intermediate and high self-reported adherence showed
      significantly better mean scores than patients with low adherence on several MS
      outcomes, including EDSS (4.1 and 4.2 vs 4.8, P<.05), MSIS physical function (33
      and 35 vs 41, P<.05), and TSQM Global Satisfaction (75 and 78 vs 70, P<.05).
      Conclusions: The findings of this study indicate that patients with MS are mostly
      adherent to their existing treatments. Patients with greater medication adherence
      may have increased cost, but their physical outcomes are better. This finding may
      shed light on other chronic disease entities and how we view the success of
      treatments.

PMID- 29181517
TI  - Musculoskeletal Disorders in Ophthalmologists After Simulated Cataract Operation:
      A Pilot Study.
AB  - Context: Musculoskeletal disorders are a common problem among ophthalmologists,
      likely due to ergonomic challenges. Most research on the topic has been survey
      based studies, which carry inherent weaknesses. Objective: To examine the
      frequency and pattern of musculoskeletal dysfunction induced by performing a
      surgical procedure and to quantify the improvement after ergonomic interventions.
      Methods: Ophthalmology residents from a single academic institution were invited
      to participate in the study on a volunteer basis. Preexisting musculoskeletal
      disorders; previous spinal, cervical, or shoulder surgery; or limited range of
      motion of the upper body or arms were exclusion criteria. The interventions
      consisted of a surgical simulation session and a control session, each lasting 2
      hours. For the surgical simulation session, a musculoskeletal examination was
      performed at the beginning and end of the 2-hour session after the participants
      used the Eyesi Cataract Surgery Simulator (VRmagic). A musculoskeletal
      examination was performed by the palpatory screener (M.A.Z.) at the beginning and
      conclusion of the 2-hour control session, which consisted of both passive and
      active tasks. The musculoskeletal screener was blinded as to which session the
      participant was completing at the time of the examinations, as well as any
      musculoskeletal examination findings from before the intervention. All
      participants completed both sessions, but they were randomized into which session
      they were to complete first. Participants completed each session one after the
      other. Results: Eight participants completed both sessions, and 32
      musculoskeletal examinations were performed. In the surgical simulation session,
      after using the simulator, 5 of 8 participants had an increase in the number of
      spinal levels with tissue texture abnormalities, and 3 had no change. Of those in
      the control session, 5 participants had a decrease in the number of spinal levels
      with tissue texture abnormalities after a period of rest. Three participants in
      the control session had an increase in the number of affected spinal levels. The
      mean (SD) change in number of affected spinal levels in the surgical simulation
      session and control session was 1.3 (1.2) and -0.6 (2.0), respectively (P=.125).
      Age, sex, level of training, baseline somatic dysfunction, and which session was
      completed first did not affect results. Conclusion: The majority of participants
      in the surgical simulation session had an increase in degree of somatic
      dysfunction, whereas the majority in the control session had a decrease in degree
      of somatic dysfunction. Although the sample size of this pilot study was too
      small to show statistical significance, a trend was observed, and further study
      is warranted.

PMID- 29181518
TI  - Benign Breast Conditions.
AB  - Breast masses and nipple discharge are common symptoms that lead women to seek
      medical care. Many of the findings on subsequent examination are benign. When
      evaluating a patient who presents with breast masses or nipple discharge, it is
      useful to take a holistic approach to evaluating the patient, including a
      detailed history, structural and directed physical examination, and, if
      indicated, laboratory studies, diagnostic imaging, and biopsy. The goal of this
      review is to assist physicians in understanding the evaluation, diagnosis, and
      management of benign breast conditions.

PMID- 29181519
TI  - Role of Antiplatelet Therapy in Stroke Prevention in Patients With Atrial
      Fibrillation.
AB  - Patients with atrial fibrillation are at increased risk of having a cardioembolic
      stroke. The use of oral anticoagulation is now well established to prevent
      strokes in patients with atrial fibrillation and a CHA2DS2-VASc (congestive heart
      failure, hypertension, age >=75 years [2 points], diabetes mellitus, prior
      stroke/transient ischemic attack or thromboembolism [2 points], vascular disease,
      age 65 to 74 years, and sex category) score of greater than 1, beyond sex.
      However, the role of antiplatelet therapy, specifically aspirin in low-risk
      patients or as an alternative to oral anticoagulation, remains controversial. The
      most recent US guidelines conflict with the European guidelines, which do not
      recommend antiplatelet monotherapy for stroke prevention irrespective of stroke
      risk. The aim of this review is to summarize published studies that question the
      role of aspirin in preventing strokes associated with atrial fibrillation.
      Overall, aspirin is found to play a limited role in the prevention of stroke in
      patients with atrial fibrillation and is associated with a similar risk of
      hemorrhagic events compared with anticoagulants. The benefit of dual antiplatelet
      therapy as an alternative to oral anticoagulation requires further study.

PMID- 29181520
TI  - Predictors of Osteopathic Medical Students' Readiness to Use Health Information
      Technology.
AB  - Context: The advent of health information technology (HIT) tools can affect the
      practice of modern medicine in many ways, ideally by improving quality of care
      and efficiency and reducing medical errors. Future physicians will play a key
      role in the successful implementation of HIT. However, osteopathic medical
      students' willingness to learn, adopt, and use technology in a health care
      setting is not well understood. Objective: To understand osteopathic medical
      students' knowledge, attitudes, and behaviors regarding HIT and to identify
      factors that may be related to their readiness to use HIT. Methods: Using a cross
      sectional approach, quantitative surveys were collected from students attending a
      large osteopathic medical school. Multivariate regression modeling was used to
      determine whether knowledge, attitudes, behaviors, and personal characteristics
      were associated with students' readiness to use HIT in future clinical practice.
      Results: Six hundred four students responded to at least 70% of the survey and
      were included in the analysis. Multivariate modeling successfully explained the
      26% of variance in predicting students' readiness to use HIT (F8,506=22.6,
      P<.001, R2=0.263). Greater self-efficacy, openness to change (in academic/work
      settings), favorable attitudes toward HIT use, mobile technology use, younger
      age, being male, and prior exposure to technology were associated with readiness
      to use HIT. Conclusion: Understanding students' level of HIT readiness may help
      guide medical education intervention efforts to better prepare future osteopathic
      physicians for HIT engagement and use. Innovative approaches to HIT education in
      medical school curricula that include biomedical informatics may be necessary.

PMID- 29181521
TI  - Osteopathic Manipulative Treatment for the Management of Adjacent Segment
      Pathology.
AB  - Adjacent segment pathology is an adverse effect of spinal fusion that
      precipitates accelerated spinal degenerative changes at vertebral segments
      contiguous with the fused vertebrae. The accelerated degeneration related to ASP
      can be challenging to manage, as it can lead to conditions such as radiculopathy
      and can create the need for reoperation. In the present case, a 50-year-old woman
      with a previous spinal fusion presented with a 1-year history of progressive low
      back pain, lumbar radiculopathy, and sciatica. Osteopathic manipulative treatment
      was used to manage her pain, and the patient reported that the treatment provided
      long-term resolution of her sciatica symptoms. This case demonstrates an
      effective use of osteopathic manipulative treatment in the conservative
      management of lumbar radiculopathy related to adjacent segment pathology.

PMID- 29181523
TI  - Vesicovaginal Fistula.

PMID- 29181522
TI  - Inguinal Herniation of Perinephric Tissue: Case Report and Review of the
      Literature.
AB  - Inguinal hernias containing a kidney or perinephric tissue are extremely rare and
      usually related to cases involving a kidney positioned in the pelvis. We report
      the case of a 79-year-old man who presented with abdominal pain and scrotal
      swelling. He was found on imaging to have an inferiorly displaced kidney with an
      inguinal herniation of Gerota fascia, as well as an obstructing ureteral stone
      with an associated forniceal rupture. The unusual renal anatomy, as well as the
      management of a forniceal rupture, is discussed.

PMID- 29181524
TI  - Challenging Case of Parotitis: A Comprehensive Approach.
AB  - The diagnosis and management of parotitis can be challenging. Patients often
      present with pain and edema in the neck, jaw, head, and ear due to congestion of
      the gland. Parotitis is typically caused by an infection within the parotid gland
      and surrounding lymph nodes, and the infection can spread to nearby cervical
      fascial planes and cause major complications if not managed successfully.
      Specific guidelines for the outpatient management of parotitis are limited, and
      outpatient treatment failures are common, requiring inpatient therapy with
      multiple broad-spectrum antibiotics. In the current case, a comprehensive patient
      centered approach was used to treat a woman whose overlapping clinical
      conditions, lifestyle, and work factors led to an infection of the parotid gland.

PMID- 29181525
TI  - OMT for Patients With Multiple Sclerosis.

PMID- 29181527
TI  - Diagnosing Resistance to a Proprotein Convertase Subtilisin/Kexin Type 9
      Inhibitor.

PMID- 29181526
TI  - Cortical Structures Associated With Human Blood Pressure Control.
AB  - Importance: A better understanding of the role of cortical structures in blood
      pressure control may help us understand cardiovascular collapse that may lead to
      sudden unexpected death in epilepsy (SUDEP). Objective: To identify cortical
      control sites for human blood pressure regulation. Design, Setting, and
      Participants: Patients with intractable epilepsy undergoing intracranial
      electrode implantation as a prelude to epilepsy surgery in the Epilepsy
      Monitoring Unit at University Hospitals Cleveland Medical Center were potential
      candidates for this study. Inclusion criteria were patients 18 years or older who
      had electrodes implanted in one or more of the regions of interest and in whom
      deep brain electrical stimulation was indicated for mapping of ictal onset or
      eloquent cortex as a part of the presurgical evaluation. Twelve consecutive
      patients were included in this prospective case series from June 1, 2015, to
      February 28, 2017. Main Outcomes and Measures: Changes in continuous,
      noninvasive, beat-by-beat blood pressure parameter responses from amygdala,
      hippocampal, insular, orbitofrontal, temporal, cingulate, and subcallosal
      stimulation. Electrocardiogram, arterial oxygen saturation, end-tidal carbon
      dioxide, nasal airflow, and abdominal and thoracic plethysmography were
      monitored. Results: Among 12 patients (7 female; mean [SD] age, 44.25 [12.55]
      years), 9 electrodes (7 left and 2 right) all in Brodmann area 25 (subcallosal
      neocortex) in 4 patients produced striking systolic hypotensive changes. Well
      maintained diastolic arterial blood pressure and narrowed pulse pressure
      indicated stimulation-induced reduction in sympathetic drive and consequent
      probable reduction in cardiac output rather than bradycardia or peripheral
      vasodilation-induced hypotension. Frequency-domain analysis of heart rate and
      blood pressure variability showed a mixed picture. No other stimulated structure
      produced significant blood pressure changes. Conclusions and Relevance: These
      findings suggest that Brodmann area 25 has a role in lowering systolic blood
      pressure in humans. It is a potential symptomatogenic zone for peri-ictal
      hypotension in patients with epilepsy.

PMID- 29181528
TI  - Mutation Spectrum of the LRP5, NDP, and TSPAN12 Genes in Chinese Patients With
      Familial Exudative Vitreoretinopathy.
AB  - Purpose: LRP5, NDP, and TSPAN12 are known to be associated with familial
      exudative vitreoretinopathy (FEVR). In this study, a comprehensive mutation
      screening for the three genes was performed in patients with a clinical diagnosis
      of FEVR in Han Chinese. Methods: Genomic DNA and clinical data were collected
      from 100 probands and their family members. Sanger sequencing was performed to
      screen for LRP5, NDP, and TSPAN12 mutations and phenotype-genotype correlation
      was analyzed. Results: There were 23 causative mutations identified in 23
      unrelated probands (10/23 in LRP5, 8/23 in TSPAN12, and 5/23 in NDP). Apart from
      NDP mutations, only two LRP5 mutations inherited in an autosomal recessive
      manner. Among the 23 causative mutations, 13 were novel variants (4/10 in LRP5,
      6/8 in TSPAN12, and 3/5 in NDP). According to the modified classification system,
      statistical significance was observed in the distribution of mutated genes (P =
      0.049). None of the causative mutations was found in group I FEVR. Probands with
      LRP5 or NDP mutations were mainly categorized into group III and IV, TSPAN12
      mutations were mainly observed in probands with group IV and V FEVR. Conclusions:
      The detection rate for mutations in the three known genes was 23%. Mutations in
      LRP5 and TSPAN12 were more frequent, accounting for 10% and 8%, respectively. The
      NDP mutations were only identified in 6% in this cohort. There were 13 novel
      variants found, which provided a deeper understanding of this disease. Potential
      phenotype-genotype correlation was observed in the modified system. TSPAN12
      mutations might lead to the most severe phenotype.

PMID- 29181529
TI  - Restaging Abdominopelvic Computed Tomography Before Surgery After Preoperative
      Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer.

PMID- 29181531
TI  - Evolving Delivery System and Market Factors and Their Influence on Physician
      Networks and Patient Care.

PMID- 29181533
TI  - Blind Obedience and an Unnecessary Workup for Hypoglycemia: A Teachable Moment.

PMID- 29181530
TI  - Neurodevelopmental and Behavioral Outcomes in Extremely Premature Neonates With
      Ventriculomegaly in the Absence of Periventricular-Intraventricular Hemorrhage.
AB  - Importance: Studies of cranial ultrasonography and early childhood outcomes among
      cohorts of extremely preterm neonates have linked periventricular
      intraventricular hemorrhage and cystic periventricular leukomalacia with adverse
      neurodevelopmental outcomes. However, the association between nonhemorrhagic
      ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully
      understood. Objective: To characterize the outcomes of extremely preterm neonates
      younger than 27 weeks' gestational age who experienced nonhemorrhagic
      ventriculomegaly that was detected prior to 36 weeks' postmenstrual age. Design,
      Setting, and Participants: This longitudinal observational study was conducted at
      16 centers of the Eunice Kennedy Shriver National Institute of Child Health and
      Human Development Neonatal Research Network. Infants born prior to 27 weeks'
      gestational age in any network facility between July 1, 2006, and June 30, 2011,
      were included if they had a cranial ultrasonogram performed prior to 36 weeks'
      postmenstrual age. Comparisons were made between those with ventriculomegaly and
      those with normal cranial sonograms. Data analysis was completed from August 2013
      to August 2017. Main Outcomes and Measures: The main outcome was
      neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler
      Development III cognitive score less than 70, moderate/severe cerebral palsy, a
      Gross Motor Function Classification System score of level 2 or more, vision
      impairment, or hearing impairment. Secondary outcomes included Bayley Scales of
      Infant and Toddler Development III subscores, components of neurodevelopmental
      impairment, behavioral outcomes, and death/neurodevelopmental impairment.
      Logistic regression was used to evaluate the association of ventriculomegaly with
      adverse outcomes while controlling for potentially confounding variables and
      center differences as a random effect. Linear regression was used similarly for
      continuous outcomes. Results: Of 4193 neonates with ultrasonography data, 300 had
      nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial ultrasonograms
      (73%), 775 had periventricular-intraventricular hemorrhage (18.5%), and 73 had
      cystic periventricular leukomalacia (1.7%). Outcomes were available for 3008 of
      3345 neonates with ventriculomegaly or normal scans (90%). Compared with normal
      cranial ultrasonograms, ventriculomegaly was associated with lower gestational
      age, male sex, and bronchopulmonary dysplasia, late-onset sepsis, meningitis,
      necrotizing enterocolitis, and stage 3 retinopathy of prematurity. After
      adjustment, neonates with ventriculomegaly had higher odds of neurodevelopmental
      impairment (odds ratio [OR], 3.07; 95% CI, 2.13-4.43), cognitive impairment (OR,
      3.23; 95% CI, 2.09-4.99), moderate/severe cerebral palsy (OR, 3.68; 95% CI, 2.08
      6.51), death/neurodevelopmental impairment (OR, 2.17; 95% CI, 1.62-2.91), but not
      death alone (OR, 1.09; 95% CI, 0.76-1.57). Behavioral outcomes did not differ.
      Conclusions and Relevance: Nonhemorrhagic ventriculomegaly is associated with
      increased odds of neurodevelopmental impairment among extremely preterm neonates.

PMID- 29181532
TI  - Management of Suspected Opioid Overdose With Naloxone in Out-of-Hospital
      Settings: A Systematic Review.
AB  - Background: Naloxone is effective for reversing opioid overdose, but optimal
      strategies for out-of-hospital use are uncertain. Purpose: To synthesize evidence
      on 1) the effects of naloxone route of administration and dosing for suspected
      opioid overdose in out-of-hospital settings on mortality, reversal of overdose,
      and harms, and 2) the need for transport to a health care facility after reversal
      of overdose with naloxone. Data Sources: Ovid MEDLINE (1946 through September
      2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S.
      Food and Drug Administration (FDA) materials, and reference lists. Study
      Selection: English-language cohort studies and randomized trials that compared
      different doses of naloxone, administration routes, or transport versus
      nontransport after reversal of overdose with naloxone. Main outcomes were
      mortality, reversal of overdose, recurrence of overdose, and harms. Data
      Extraction: Dual extraction and quality assessment of individual studies;
      consensus assessment of overall strength of evidence (SOE). Data Synthesis: Of 13
      eligible studies, 3 randomized controlled trials and 4 cohort studies compared
      different administration routes. At the same dose (2 mg), 1 trial found similar
      efficacy between higher-concentration intranasal naloxone (2 mg/mL) and
      intramuscular naloxone, and 1 trial found that lower-concentration intranasal
      naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was
      associated with decreased risk for agitation (low SOE). Evidence was insufficient
      to evaluate other comparisons of route of administration. Six uncontrolled
      studies reported low rates of death and serious adverse events (0% to 1.25%) in
      nontransported patients after successful naloxone treatment. Limitation: There
      were few studies, all had methodological limitations, and none evaluated FDA
      approved autoinjectors or highly concentrated intranasal formulations.
      Conclusion: Higher-concentration intranasal naloxone (2 mg/mL) seems to have
      efficacy similar to that of intramuscular naloxone for reversal of opioid
      overdose, with no difference in adverse events. Nontransport after reversal of
      overdose with naloxone seems to be associated with a low rate of serious harms,
      but no study evaluated risks of transport versus nontransport. Primary Funding
      Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).

PMID- 29181535
TI  - Face the Facts: We Need to Change the Way We Do Pay for Performance.

PMID- 29181534
TI  - Association Between Decline in Slow Vital Capacity and Respiratory Insufficiency,
      Use of Assisted Ventilation, Tracheostomy, or Death in Patients With Amyotrophic
      Lateral Sclerosis.
AB  - Importance: The prognostic value of slow vital capacity (SVC) in relation to
      respiratory function decline and disease progression in patients with amyotrophic
      lateral sclerosis (ALS) is not well understood. Objective: To investigate the
      rate of decline in percentage predicted SVC and its association with respiratory
      related clinical events and mortality in patients with ALS. Design, Setting, and
      Participants: This retrospective study included 893 placebo-treated patients from
      2 large clinical trials (EMPOWER and BENEFIT-ALS, conducted from March 28, 2011,
      to November 1, 2012, and from October 23, 2012, to March 21, 2014, respectively)
      and an ALS trial database (PRO-ACT, containing studies completed between 1990 and
      2010) to investigate the rate of decline in SVC. Data from the EMPOWER trial
      (which enrolled adults with possible, probable, or definite ALS; symptom onset
      within 24 months before screening; and upright SVC at least 65% of predicted
      value for age, height, and sex) were used to assess the relationship of SVC to
      respiratory-related clinical events; 456 patients randomized to placebo were used
      in this analysis. The 2 clinical trials included patients from North America,
      Australia, and Europe. Main Outcomes and Measures: Clinical events included the
      earlier of time to death or time to decline in the Amyotrophic Lateral Sclerosis
      Functional Rating Scale-Revised (ALSFRS-R) respiratory subdomain, time to onset
      of respiratory insufficiency, time to tracheostomy, and all-cause mortality.
      Results: Among 893 placebo-treated patients with ALS, the mean (SD) patient age
      was 56.7 (11.2) years, and the mean (SD) SVC was 90.5% (17.1%) at baseline; 65.5%
      (585 of 893) were male, and 20.5% (183 of 893) had bulbar-onset ALS. In EMPOWER,
      average decline of SVC from baseline through 1.5-year follow-up was -2.7
      percentage points per month. Steeper declines were found in patients older than
      65 years (-3.6 percentage points per month [P = .005 vs <50 years and P = .007 vs
      50-65 years) and in patients with an ALSFRS-R total score of 39 or less at
      baseline (-3.1 percentage points per month [P < .001 vs >39]). When the rate of
      decline of SVC was slower by 1.5 percentage points per month in the first 6
      months, risk reductions for events after 6 months were 19% for decline in the
      ALSFRS-R respiratory subdomain or death after 6 months, 22% for first onset of
      respiratory insufficiency or death after 6 months, 23% for first occurrence of
      tracheostomy or death after 6 months, and 23% for death at any time after 6
      months (P < .001 for all). Conclusions and Relevance: The rate of decline in SVC
      is associated with meaningful clinical events in ALS, including respiratory
      failure, tracheostomy, or death, suggesting that it is an important indicator of
      clinical progression.

PMID- 29181536
TI  - Pharmacologic Treatment of Seasonal Allergic Rhinitis: Synopsis of Guidance From
      the 2017 Joint Task Force on Practice Parameters.
AB  - Description: The Joint Task Force on Practice Parameters, which comprises
      representatives of the American Academy of Allergy, Asthma and Immunology (AAAAI)
      and the American College of Allergy, Asthma and Immunology (ACAAI), formed a
      workgroup to review evidence and provide guidance to health care providers on the
      initial pharmacologic treatment of seasonal allergic rhinitis in patients aged 12
      years or older. Methods: To update a prior systematic review, the workgroup
      searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials
      from 18 July 2012 to 29 July 2016 to identify studies that addressed efficacy and
      adverse effects of single or combination pharmacotherapy for seasonal allergic
      rhinitis. In conjunction with the Joint Task Force, the workgroup reviewed the
      evidence and developed recommendations about initial treatment approaches by
      using the Grading of Recommendations Assessment, Development and Evaluation
      approach. Members of the AAAAI, the ACAAI, and the general public provided
      feedback on the draft document, which the Joint Task Force reviewed before
      finalizing the guideline. Recommendation 1: For initial treatment of seasonal
      allergic rhinitis in persons aged 12 years or older, routinely prescribe
      monotherapy with an intranasal corticosteroid rather than an intranasal
      corticosteroid in combination with an oral antihistamine. (Strong
      recommendation). Recommendation 2: For initial treatment of seasonal allergic
      rhinitis in persons aged 15 years or older, recommend an intranasal
      corticosteroid over a leukotriene receptor antagonist. (Strong recommendation).
      Recommendation 3: For treatment of moderate to severe seasonal allergic rhinitis
      in persons aged 12 years or older, the clinician may recommend the combination of
      an intranasal corticosteroid and an intranasal antihistamine for initial
      treatment. (Weak recommendation).

PMID- 29181537
TI  - A Multivariate Analytic Approach to the Differential Diagnosis of Apraxia of
      Speech.
AB  - Purpose: Apraxia of speech (AOS) is a consequence of stroke that frequently co
      occurs with aphasia. Its study is limited by difficulties with its perceptual
      evaluation and dissociation from co-occurring impairments. This study examined
      the classification accuracy of several acoustic measures for the differential
      diagnosis of AOS in a sample of stroke survivors. Method: Fifty-seven individuals
      were included (mean age = 60.8 +/- 10.4 years; 21 women, 36 men; mean months
      poststroke = 54.7 +/- 46). Participants were grouped on the basis of
      speech/language testing as follows: AOS-Aphasia (n = 20), Aphasia Only (n = 24),
      and Stroke Control (n = 13). Normalized Pairwise Variability Index, proportion of
      distortion errors, voice onset time variability, and amplitude envelope
      modulation spectrum variables were obtained from connected speech samples.
      Measures were analyzed for group differences and entered into a linear
      discriminant analysis to predict diagnostic classification. Results: Out-of
      sample classification accuracy of all measures was over 90%. The envelope
      modulation spectrum variables had the greatest impact on classification when all
      measures were analyzed together. Conclusions: This study contributes to efforts
      to identify objective acoustic measures that can facilitate the differential
      diagnosis of AOS. Results suggest that further study of these measures is
      warranted to determine the best predictors of AOS diagnosis. Supplemental
      Materials: https://doi.org/10.23641/asha.5611309.

PMID- 29181538
TI  - Data Deficiency in an Era of Expanding Neonatal Intensive Care Unit Care.

PMID- 29181539
TI  - Is It Time for a New Medical Specialty?: The Medical Virtualist.

PMID- 29181540
TI  - Physician Denial of Inappropriate Patient Requests-What If I Say No??

PMID- 29181541
TI  - Emergency Medical Services Naloxone Administration: Many Unknowns and
      Opportunities.

PMID- 29181542
TI  - Association of Clinician Denial of Patient Requests With Patient Satisfaction.
AB  - Importance: Prior studies suggesting clinician fulfillment or denial of requests
      affects patient satisfaction included limited adjustment for patient confounders.
      The studies also did not examine distinct request types, yet patient expectations
      and clinician fulfillment or denial might vary among request types. Objective: To
      examine how patient satisfaction with the clinician is associated with clinician
      denial of distinct types of patient requests, adjusting for patient
      characteristics. Design, Setting, and Participants: Cross-sectional observational
      study of 1319 outpatient visits to family physicians (n = 56) by 1141 adults at
      one Northern California academic health center. Main Outcomes and Measures: We
      used 6 Consumer Assessment of Healthcare Providers and Systems Clinician and
      Group Adult Visit Survey items to measure patient satisfaction with the visit
      physician. Standardized items were averaged to form the satisfaction score
      (Cronbach alpha = 0.80), which was then percentile-transformed. Seven separate
      linear mixed-effects models examined the adjusted mean differences in patient
      satisfaction percentile associated with denial of each of the following requests
      (if present)-referral, pain medication, antibiotic, other new medication,
      laboratory test, radiology test, or other test-compared with fulfillment of the
      respective requests. The models adjusted for patient sociodemographics, weight,
      health status, personality, worry over health, prior visit with clinician, and
      the other 6 request categories and their dispositions. Results: The mean (SD) age
      of the 1141 patients was 45.6 (16.1) years, and 902 (68.4%) were female. Among
      1319 visits, 897 (68.0%) included at least 1 request; 1441 (85.2%) were
      fulfilled. Requests by category were referral, 294 (21.1%); pain medication, 271
      (20.5%); antibiotic, 107 (8.1%); other new medication, 271 (20.5%); laboratory
      test, 448 (34.0%); radiology test, 153 (11.6%); and other tests, 147 (11.1%).
      Compared with fulfillment of the respective request type, clinician denials of
      requests for referral, pain medication, other new medication, and laboratory test
      were associated with worse satisfaction (adjusted mean percentile differences, 
      19.75 [95% CI, -30.75 to -8.74], -10.72 [95% CI, -19.66 to -1.78], -20.36 [95%
      CI, -29.54 to -11.18], and -9.19 [95% CI, -17.50 to -0.87]), respectively.
      Conclusions and Relevance: Clinician denial of some types of requests was
      associated with worse patient satisfaction with the clinician, but not for
      others, when compared with fulfillment of the requests. In an era of patient
      satisfaction-driven compensation, the findings suggest the need to train
      clinicians to deal effectively with requests, potentially enhancing patient and
      clinician experiences.

PMID- 29181544
TI  - Angiotensin 1-7, but not the thrombin-cleaved osteopontin C-terminal fragment,
      attenuates osteopontin-mediated macrophage-induced endothelial-cell inflammation.
AB  - OBJECTIVE AND DESIGN: Evaluating the pro-/anti-inflammatory activity of the C
      terminal cleavage product of osteopontin in comparison to angiotensin 1-7.
      MATERIAL AND SUBJECTS: Human coronary endothelial cells (hcEC) treated with
      conditioned media from human U937 macrophages. TREATMENT: Macrophages were
      (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN
      FL, OPN-N, respectively), angiotensin II, angiotensin 1-7 or TNF-alpha. OPN-C
      modulatory capacity was compared to that of Ang1-7 in inhibiting subsequent Ag
      II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation.
      METHODS: Protein expression of NFkappaB, IkappaB, vCAM-1 and iCAM-1 was assessed
      using western blot. Promotor activation by NFkappaB was also assessed by dual
      luciferase reporter assay. RESULTS: Conditioned media of macrophages treated with
      OPN-C induced hcECs' NfkappaB activation to a lower degree than OPN-FL or OPN-N.
      Priming of macrophages with angiotensin 1-7 attenuated the endothelial pro
      inflammatory effect induced by subsequent exposure of the macrophages to
      angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfkappaB activation
      and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not
      significantly attenuate the subsequent response to the pro-inflammatory
      cytokines. CONCLUSIONS: OPN-C induces lower macrophage-induced endothelial
      inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1-7, fails to
      prevent endothelial inflammation induced by subsequent pro-inflammatory
      macrophage stimulation.

PMID- 29181545
TI  - Non-celiac gluten sensitivity: people without celiac disease avoiding gluten-is
      it due to histamine intolerance?
AB  - INTRODUCTION: Food intolerance/malabsorption is caused by food ingredients,
      carbohydrates (mainly lactose and fructose), proteins (gluten), and biogenic
      amines (histamine) which cause nonspecific gastrointestinal and extra-intestinal
      symptoms. Here we focus on possible etiologic factors of
      intolerance/malabsorption especially in people with non-celiac gluten sensitivity
      (NCGS) or the so-called people without celiac disease avoiding gluten (PWCDAG)
      and histamine intolerance. METHODS: Recognizing the recently described symptoms
      of NCGS (PWCDAG) we review correlations and parallels to histamine intolerance
      (HIT). RESULTS: We show that intestinal and extra-intestinal NCGS (PWCDAG)
      symptoms are very similar to those which can be found in histamine intolerance.
      CONCLUSIONS: After a detailed diagnostic workup for all possible etiologic
      factors in every patient, a targeted dietary intervention for single or possibly
      combined intolerance/malabsorption might be more effective than a short-term diet
      low in fermentable oligo-, di- and monosaccharides and polyols (FODMAP) or the
      untargeted uncritical use of gluten-free diets.

PMID- 29181546
TI  - [Neurolymphomatosis : Two case reports].

PMID- 29181547
TI  - Fine-mapping and identifying candidate genes conferring resistance to Soybean
      mosaic virus strain SC20 in soybean.
AB  - KEY MESSAGE: The Mendelian gene conferring resistance to Soybean mosaic virus
      Strain SC20 in soybean was fine-mapped onto a 79-kb segment on Chr.13 where two
      closely linked candidate genes were identified and qRT-PCR verified. Soybean
      mosaic virus (SMV) threatens the world soybean production, particularly in China.
      A country-wide SMV strain system composed of 22 strains was established in China,
      among which SC20 is a dominant strain in five provinces in Southern China.
      Resistance to SC20 was evaluated in parents, F1, F2 and the F2:7 RIL (recombinant
      inbred line) population derived from a cross between Qihuang-1 (resistant) and
      NN1138-2 (susceptible). The segregation ratio of resistant to susceptible in the
      populations suggested a single dominant gene involved in the resistance to SC20
      in Qihuang-1. A "partial genome mapping strategy" was used to map the resistance
      gene on Chromosome 13. Linkage analysis between 178 RILs and genetic markers
      showed that the SC20-resistance gene located at 3.9 and 3.8 cM to the flanking
      markers BARCSOYSSR_13_1099 and BARCSOYSSR_13_1185 on Chromosome 13. Subsequently,
      a residual heterozygote segregating population with 346 individuals was developed
      by selfing four plants heterozygous at markers adjacent to the tentative SC20
      resistance gene; then, the candidate region was delimited to a genomic interval
      of approximately 79 kb flanked by the new markers gm-ssr_13-14 and gm-indel_13-3.
      Among the seven annotated candidate genes in this region, two genes,
      Glyma.13G194700 and Glyma.13G195100, encoding Toll Interleukin Receptor
      nucleotide-binding-leucine-rich repeat resistance proteins were identified as
      candidate resistance genes by quantitative real-time polymerase chain reaction
      and sequence analysis. The two closely linked genes work together to cause the
      phenotypic segregation as a single Mendelian gene. These results will facilitate
      marker-assisted selection, gene cloning and breeding for the resistance to SC20.

PMID- 29181548
TI  - Non-driver mutations in patients with JAK2V617F-mutated polycythemia vera or
      essential thrombocythemia with long-term molecular follow-up.
AB  - JAK2V617F monitoring and NGS of non-driver genes was performed in 100 patients
      with polycythemia vera (PV) or essential thrombocythemia (ET) with long molecular
      follow-up. Patients who did not progress to myelofibrosis (MF) or acute myeloid
      leukemia (AML) after more than 10 years (n = 50) showed a low frequency of
      mutations at first sample (18%) and an incidence rate of 1.7 new mutations * 100
      person-years. Mutations were detected at first sample in 83% of PV/ET patients
      who later progressed to AML (n = 12) with these patients having a rate of 25.6
      mutations * 100 person-years. Presence of mutations at diagnosis was the unique
      risk factor for acquiring a new genetic event (HR 2.7, 95% CI 1.1-6.8, p = 0.03)
      after correction for age, PV diagnosis, and total duration of hydroxyurea (HU)
      exposure. Patients with additional mutation at first sample showed a higher
      probability of developing cytopenia under HU therapy and a higher risk of AML (HR
      12.2, 95% CI 2.6-57.1, p = 0.001) with mutations in ASXL1 (p < 0.0001), TP53 (p =
      0.01), SRSF2 (p < 0.0001), IDH1/2 (p < 0.0001), and RUNX1 (p < 0.0001) being
      associated with a higher probability of AML. Myelofibrotic transformation was
      more frequent in patients with additional mutations, especially in SF3B1 (p =
      0.02) and IDH1/2 (p < 0.0001) although a persistently high or a progressive
      increase of the JAK2V617F allele burden while receiving cytoreduction was the
      strongest predictor of MF transformation (HR 10.8, 95% CI 2.4-49.1, p = 0.002).
      In conclusion, NGS may be useful to identify a minority of PV and ET patients
      with high genetic instability and increased risk of AML transformation.

PMID- 29181549
TI  - Treating open lower limb fractures successfully; thoughts and current practice on
      therapy and centralization in The Netherlands.
AB  - INTRODUCTION: The British Orthopedic Association (BOA) and British Association of
      Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) updated the evidence
      based guidelines for the treatment and care of open lower limb fractures (BOAST
      4). Following this, a Dutch version has been developed. The main points are
      multidisciplinary care, planning, and treatment of these injuries. Early
      osteosynthesis (within 7-14 days) combined with soft-tissue coverage results in
      more efficient care and less complications. AIM: To study the variation in
      treatment and thoughts among trauma, orthopedic, and plastic surgeons. MATERIALS
      AND METHODS: In this cross-sectional study 94 surgeons (57 trauma, 23 plastic,
      and 14 orthopedic surgeons) working at 46 centers completed an online
      questionnaire, consisting of 5 demographic, 14 hospital-related, 8 BOAST 4
      related, and 2 centralization-related questions. RESULTS: There was a strong
      agreement among surgeons about the best moment for multidisciplinary
      consultation, which was before initial debridement, while in practice, this often
      does not occur. All surgeons agreed that the initial debridement should be
      performed immediately by any surgeon, but not solely by trainees. Plastic
      surgeons responded that the definitive stabilization and wound cover should not
      exceed 7 days, while half of the trauma and orthopedic surgeons agreed that it
      should not exceed 14 days. Finally, most surgeons agreed that Gustilo 3 fractures
      should be centralized. However, there was disagreement on the need for
      centralization of Gustilo 2 fractures. DISCUSSION: Surgeons agree on better and
      earlier multidisciplinary treatment of open lower limb fractures and the
      centralization of Gustilo 3 fractures.

PMID- 29181550
TI  - Intravesical hyaluronic acid and chondroitin sulfate for recurrent urinary tract
      infections: systematic review and meta-analysis.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to assess the efficacy of
      intravesical hyaluronic acid (HA) and chondroitin sulfate (CS), alone or in
      combination, for recurrent urinary tract infections (RUTIs) in adult female
      patients using a systematic review and meta-analysis. METHODS: English-language
      articles were obtained from the MEDLINE, Embase, and Cochrane databases through
      November 2016, by manual searching and cross-referencing. Randomized and
      nonrandomized trials of adult female patients with a documented history of RUTIs
      who received HA, CS or HA plus CS were included. The random effects model was
      applied to all pooled analyses. Risk of bias was assessed for individual studies
      and across studies. RESULTS: Two randomized (n = 85) and six nonrandomized (n =
      715) studies met the inclusion criteria. These studies assessed HA +/- CS;
      studies of CS alone were not identified in the search. HA +/- CS decreased the
      UTI rate per patient-year (pooled mean difference [MD] -2.56; 95% confidence
      interval [CI] -3.86, -1.26; p < 0.001) and increased the time to first UTI
      recurrence (pooled MD 130.05 days; 95% CI 5.84, 254.26; p = 0.04). There was
      heterogeneity in most outcomes considered, and publication bias in many studies.
      The standard of trial reporting was low. The patient population size, and the
      number of studies included, were small. CONCLUSIONS: HA +/- CS appears to reduce
      the rate of UTI and increase the time to recurrence in women with RUTI. As
      randomized controlled studies are available only for HA plus CS, the quality of
      evidence is higher for the combination than for HA alone.

PMID- 29181551
TI  - [Metabolic disorders as paraneoplastic syndromes].
AB  - Paraneoplastic syndromes are characterized by the tumor-induced release of
      peptide hormones and/or the initiation of immune phenomena, which elicit clinical
      changes and alterations in laboratory parameters independent of the tumor size
      and spread. In addition to neurological, endocrinal and rheumatological
      phenotypes, metabolic alterations play a special role in the clinical routine as
      they commonly present with acute symptoms in an emergency situation and
      necessitate immediate diagnosis and prompt initiation of treatment. Metabolic
      alterations within the framework of malignant diseases should be treated in a
      multidisciplinary team and it is often necessary to perform monitoring and
      treatment in an intensive care unit. This article focuses on the diagnostic and
      therapeutic options for metabolic disorders due to paraneoplastic syndromes, such
      as hypercalcemia, hypocalcemia, hyperglycemia, hypoglycemia and a special variant
      of tumor-induced metabolic disorders due to tumor lysis syndrome.

PMID- 29181552
TI  - [Nephrotic syndrome and microhematuria in a patient with nutcracker syndrome:
      Report of a case and review of the literature].
AB  - We report about a 43-year-old woman with polyvalent drug addiction (i.e. alcohol,
      nicotine, methadone maintenance program with parallel consumption of heroin) who
      presented to the emergency department with peripheral edema, generalized
      weakness, and arthralgia. Laboratory findings revealed, among others,
      proteinuria, hyperlipoproteinemia and hypoproteinemia defining nephrotic
      syndrome. Computed tomography of the abdomen and iliocavography further revealed
      compression of left renal vein between aorta and superior mesenteric artery with
      distention of left ovarian vein as a possible cause of nephrotic syndrome (i. e.
      nutcracker syndrome). After excluding other possible causes of nephrotic
      syndrome, we decided against an interventional procedure due to poor compliance
      of the patient and potential risk of secondary stent dislocation. Instead, we
      opted for a surgical approach (i. e. veno-venous bypass, meaning transposition of
      left vena ovarica on vena cava inferior). The operative and postoperative course
      was uneventful. Postoperatively, proteinuria, microhematuria, arthralgia and
      edema receded.

PMID- 29181553
TI  - [CAREFul-care programme for the last days of life].

PMID- 29181554
TI  - [Cardiological functional diagnostics].
AB  - Cardiovascular diseases are common; therefore, adequate and guideline-based
      diagnostics and treatment are essential. In addition to an electrocardiogram
      (ECG) and (treadmill) exercise tests, echocardiography plays the pivotal role in
      functional cardiac testing. It is permanently available at the bedside and has a
      high diagnostic accuracy; however, examinations such as cardiac magnetic
      resonance imaging (MRI) and computed tomography (CT) as well as nuclear medical
      imaging, e.g. single proton emission CT (SPECT) and positron emission tomography
      (PET) are becoming more and more common in clinical practice. This is due to the
      wide range of additional information and the high diagnostic accuracy. In the
      following article, the individual possibilities of non-invasive cardiac
      functional testing are presented and their meaningful application will be
      discussed; however, studies on the meaningful application of non-invasive
      diagnostics are scarce.

PMID- 29181555
TI  - Predicting vection and visually induced motion sickness based on spontaneous
      postural activity.
AB  - Evidence is mounting that differences in postural instability can be used to
      predict who will experience strong illusory self-motions (vection) and become
      sick when exposed to global patterns of optical flow (e.g., Apthorp et al., PLoS
      One 9(12):e113897, 2014; Stoffregen and Smart, Brain Res Bull 47:437-448, 1998).
      This study compared the predictive ability of traditional and recurrence
      quantification analysis (RQA) based measures of postural activity. We initially
      measured spontaneous fluctuations in the centre of foot pressure (CoP) of our
      subjects as they stood quietly with their eyes open and closed. They were then
      repeatedly exposed to two different types of self-motion display. As expected,
      the oscillating self-motion displays were found to induce stronger vection and
      greater sickness than the smooth self-motion displays. RQA based measures of
      spontaneous postural activity proved to be superior predictors of both vection
      strength and visually induced motion sickness (VIMS). Participants who had
      displayed lower CoP recurrence rates when standing quietly were more likely to
      later report stronger vection and VIMS when exposed to both types of optical
      flow. Vection strength (but not VIMS) was also found to correlate significantly
      with three other RQA based measures of postural activity (determinism, entropy,
      and average diagonal line length). We propose that these RQA based measures of
      spontaneous postural activity could serve as useful diagnostic tools for
      evaluating who will benefit the most/least from exposure to virtual environments.

PMID- 29181556
TI  - Oligometastases in prostate cancer : Metabolic response in follow-up PSMA-PET-CTs
      after hypofractionated IGRT.
AB  - BACKGROUND: Prostate-specific membrane antigen positron emission
      tomography/computed tomography (PSMAPET/CT) is a new and evolving diagnostic
      method in prostate cancer with special impact on treatment planning in image
      guided radiotherapy (IGRT). Initial results of metabolic response in repeated
      PSMA PET/CTs after hypofractionated IGRT for metastatic lesions are reported
      here. MATERIALS AND METHODS: Of 280 patients investigated with 68Ga-PSMA PET/CT
      in the period from 01/2014 through 12/2016 in the authors' department, patients
      were selected according to the following criteria: oligometastatic disease at
      initial PSMA PET/CT defined as not more than five metastatic lesions,
      hypofractionated IGRT to all lesions, no systemic therapy in the last 6 months
      and during follow-up, and at least one follow-up PSMA PET after radiotherapy.
      Radiotherapy was administered to all PSMA PET-detected lesions (CTV = PET-GTV + 1
      to 2 mm), mostly with 35 Gy in five fractions (one lesion with four fractions of
      7 Gy due to dose constraints, two lymph nodes with 50 Gy in 25 fractions to an
      extended volume plus a boost of 7 Gy * 2 to the PET-positive volume). Metabolic
      response of irradiated lesions was evaluated on repeated PSMA PET/CTs according
      to PERCIST criteria. Five patients with a total number of 12 PSMA PETs matched
      the criteria. Patients received radiotherapy to all PET-positive lesions and had
      at least one (in one case three) follow-up PSMA PET examinations after
      radiotherapy with an interval to the first PET of 2-15 months; the median follow
      up for all patients was 11 months. RESULTS: The mean prostate-specific antigen
      (PSA) values at the time of examination were 8.9 +/- 8.5 ng/ml (median 3.3 ng/ml,
      range 0.17-21.8 ng/ml). A total number of 18 metastatic deposits were detected.
      The PET-positive tumor volume was 5.9 +/- 13.3 cm3 (median 1.25 cm3). The mean
      standardized uptake value (mean SUVmax) of the 18 metastatic lesions decreased
      from 19.9 +/- 23.3 (mean +/- SD) prior to RT to 5.4 +/- 4.6 at post-radiotherapy
      PSMA PET/CT. Using PERCIST criteria, 14 lesions (78%) showed a metabolic response
      in PSMA PET with a reduction of SUV of at least 30%, as well as a significant
      decrease in lesion size; in seven of these lesions, no uptake of 68Ga-PSMA was
      detectable. In follow-up PET scans, only two lesions showed metabolic progression
      with an increase in SUVmax yielding a local progression-free survival of 88%
      after 1 year. There was a correlation between the time interval after
      radiotherapy (median 3 months, range 1-9 months) and response (p = 0.04) with
      better metabolic response after longer follow-up. CONCLUSIONS: Preliminary
      results of this study show high metabolic response rates of PSMA PET-positive
      metastatic lesions after hypofractionated radiotherapy in follow-up PSMA PET with
      promising local control rates. An interval of several months may be required to
      fully estimate the efficacy of radiotherapy in control PSMA PET.

PMID- 29181559
TI  - Compensation after treatment for anterior cruciate ligament injuries: a review of
      compensation claims in Norway from 2005 to 2015.
AB  - PURPOSE: To assess the most common reasons for complaints following anterior
      cruciate ligament (ACL) injuries reported to the Norwegian System of Patient
      Injury Compensation (NPE), and to view these complaints in light of the ACL
      reconstructions (ACL-Rs) reported to the Norwegian Knee Ligament Registry (NKLR).
      METHOD: Data from the NPE and the NKLR were collected for the study period (2005
      2015). The age and gender and type of complaint and reason for granted
      compensation were collected from the NPE, while the graft choice and total number
      of ACL-R were collected from the NKLR. Risk for successful grant was estimated
      for graft type. RESULTS: 18,810 primary ACL-Rs were reported to the NKLR during
      the study period. A hamstring graft was used in 12,437 (66.1%) but the bone
      patellar tendon-bone (BPTB) became the graft of choice at the end of the study
      period. 240 patients filed a complaint to the NPE, of which 101 were granted
      compensation. The odds ratio for a claim being granted following a hamstring
      graft was 2.9 compared to that of a BPTB graft (p = 0.002) The most common reason
      for compensation was a hospital-acquired infection in 39 patients (38.6%)
      followed by inadequate surgical technique (27, 26.7%) and delayed diagnosis (13,
      12.9%). Of the 39 patients with infection, 27 had received a hamstring graft and
      six a BPTB graft (two patients were not reconstructed, data missing for three
      patients). Of the 27 patients who were granted compensation due to inadequate
      surgical technique, 24 had received a hamstring graft and three a BPTB graft.
      CONCLUSION: Infection and inadequate surgical technique are the most common
      causes for granted compensation from the NPE following ACL injury. Hamstring
      grafts have a threefold risk of complication that yields compensation from the
      NPE compared to BPTB grafts. This information is relevant for patients and
      surgeons when choosing graft type. The trend of increased use of BPTB grafts is
      warranted based on the results from this study. LEVEL OF EVIDENCE: Level III.

PMID- 29181558
TI  - Internal-external malalignment of the femoral component in kinematically aligned
      total knee arthroplasty increases tibial force imbalance but does not change
      laxities of the tibiofemoral joint.
AB  - PURPOSE: The purposes of this study were to quantify the increase in tibial force
      imbalance (i.e. magnitude of difference between medial and lateral tibial forces)
      and changes in laxities caused by  2 degrees  and 4 degrees  of internal-external
      (I-E) malalignment of the femoral component in kinematically aligned total knee
      arthroplasty. Because I-E malalignment would introduce the greatest changes to
      the articular surfaces near 90 degrees  of flexion, the hypotheses were that the
      tibial force imbalance would be significantly increased near 90 degrees  flexion
      and that primarily varus-valgus laxity would be affected near 90 degrees 
      flexion. METHODS: Kinematically aligned TKA was performed on ten human cadaveric
      knee specimens using disposable manual instruments without soft tissue release.
      One 3D-printed reference femoral component, with unmodified geometry, was aligned
      to restore the native distal and posterior femoral joint lines. Four 3D-printed
      femoral components, with modified geometry, introduced I-E malalignments of 2
      degrees  and 4 degrees  from the reference component. Medial and lateral tibial
      forces were measured from 0 degrees  to 120 degrees  flexion using a custom
      tibial force sensor. Bidirectional laxities in four degrees of freedom were
      measured from 0 degrees  to 120 degrees  flexion using a custom load application
      system. RESULTS: Tibial force imbalance increased the greatest at 60 degrees 
      flexion where a regression analysis against the degree of I-E malalignment
      yielded sensitivities (i.e. slopes) of 30 N/ degrees  (medial tibial force >
      lateral tibial force) and 10 N/ degrees  (lateral tibial force > medial tibial
      force) for internal and external malalignments, respectively. Valgus laxity
      increased significantly with the 4 degrees  external component with the greatest
      increase of 1.5 degrees  occurring at 90 degrees  flexion (p < 0.0001).
      CONCLUSION: With the tibial component correctly aligned, I-E malalignment of the
      femoral component caused significant increases in tibial force imbalance.
      Minimizing I-E malalignment lowers the increase in the tibial force imbalance. By
      keeping the resection thickness of each posterior femoral condyle to within +/-
      0.5 mm of the thickness of the respective posterior region of the femoral
      component, the increase in imbalance can be effectively limited to 38 N.
      Generally laxities were unaffected within the +/- 4o range tested indicating that
      instability is not a clinical concern and that manual testing of laxities is not
      useful to detect I-E malalignment.

PMID- 29181560
TI  - Stability and alignment do not improve by using patient-specific instrumentation
      in total knee arthroplasty: a randomized controlled trial.
AB  - PURPOSE: The primary aim of the study was to examine stability and alignment
      after total knee arthroplasty (TKA) using patient-specific instrumentation (PSI)
      and conventional instrumentation (CI). The hypothesis was that stability and
      alignment would be better using PSI than CI, 12 months postoperatively. The
      secondary aim included the evaluation of clinical outcomes after TKA. METHODS: In
      this prospective randomized controlled trial, 42 patients with knee
      osteoarthritis received a Genesis II PS prosthesis with either PSI or CI.
      Patients visited the hospital preoperatively and postoperatively after 6 weeks
      and 3 and 12 months. To evaluate stability, varus-valgus laxity was determined in
      extension and flexion using stress radiographs 12 months postoperatively. Three
      months postoperatively, a long-leg radiograph and CT scan were obtained to
      measure hip-knee-ankle (HKA) alignment and component rotation. Furthermore,
      frontal and sagittal alignment of the components, the Knee Society Score, VAS
      Pain, VAS Satisfaction, Knee injury and Osteoarthritis Outcome score, Patella
      score (Kujala), University of California Los Angeles activity score, anterior
      posterior laxity, (serious) adverse device-related events, and intraoperative
      complications were reported. The clinical outcomes were compared using
      independent t tests or non-parametric alternatives, and repeated measurements
      ANOVA with a significance level of p < 0.05. RESULTS: No significant differences
      were found between the two groups regarding stability, HKA angle, and rotational
      alignment. In four patients, the PSI did not fit correctly on the tibia and/or
      femur requiring intraoperative modifications. Both groups improved significantly
      over time on all clinical outcomes, with no significant differences between the
      groups 12 months postoperatively. The PSI group showed less tibial slope than the
      patients in the CI group [PSI 2.6 degrees  versus CI 4.8 degrees  (p = 0.02)].
      Finally, the PSI group more frequently received a thinner insert size than the CI
      group (p = 0.03). CONCLUSIONS: Patients operated with PSI did not differ from CI
      in terms of stability and alignment. However, in the PSI group ligament releases
      were more often required intraoperatively. Furthermore, the two methods did not
      show different clinical results. It seems that the preoperative planning for the
      PSI facilitates more conservative bone cuts than CI, but whether this is
      clinically relevant should be investigated. Since PSI is more expensive and time
      consuming than CI, and does not outperform CI with regard to clinical results, we
      recommend to use CI. LEVEL OF EVIDENCE: I.

PMID- 29181561
TI  - Humeral lengthening and proximal deformity correction with monorail external
      fixator in young adults.
AB  - PURPOSE: Several humeral lengthening or simultaneous deformity corrections
      through one osteotomy using various external fixators were reported, while
      literature regarding correction of shortening and proximal varus deformity is
      scarce. This retrospective clinical study evaluated the results of preforming an
      acute correction and delayed lengthening in young adults through two osteotomies
      using monorail external fixator. METHODS: We report seven patients with various
      pathologies who underwent humeral proximal deformity correction and lengthening
      between 2009 and 2015. Pre-operative and post-operative clinical and radiographic
      data were collected. The mean follow-up time was 33.4 months (25-46 months).
      RESULTS: The humeral neck-shaft angle improved from 97.9 degrees  (85-110 degrees
      ) to 138.6 degrees  (135-145 degrees ). The magnitude of lengthening achieved was
      average 7.6 cm (range, 6-10 cm) at an average healing index of lengthening of
      30.2 days/cm (range, 27.7-35.4 days/cm). There was a significant increase in
      range of shoulder abduction, and active abduction improved from pre-operative
      136.4 degrees  (range, 95-160 degrees ) to post-operative 166.4 degrees  (range,
      150-180 degrees ). The DASH score improved significance from 23.29 +/- 8.36 to
      6.57 +/- 3.65 (t = 4.848; p < 0.001). CONCLUSION: Acute deformity correction and
      gradual lengthening with the monorail external fixator can be used for humeral
      shortening and proximal varus angular deformity. Functional improvement is
      expected after surgery and post-operative therapy.

PMID- 29181557
TI  - A tailored multicomponent program to reduce discomfort in critically ill
      patients: a cluster-randomized controlled trial.
AB  - PURPOSE: Critically ill patients are exposed to stressful conditions and
      experience several discomforts. The primary objective was to assess whether a
      tailored multicomponent program is effective for reducing self-perceived
      discomfort. METHODS: In a cluster-randomized two-arm parallel trial, 34 French
      adult intensive care units (ICUs) without planned interventions to reduce
      discomfort were randomized, 17 to the arm including a 6-month period of program
      implementation followed by a 6-month period without the program (experimental
      group), and 17 to the arm with an inversed sequence (control group). The tailored
      multicomponent program consisted of assessment of ICU-related self-perceived
      discomforts, immediate and monthly feedback to healthcare teams, and site
      specific tailored interventions. The primary outcome was the overall discomfort
      score derived from the 16-item IPREA questionnaire (0, minimal, 100, maximal
      overall discomfort) and the secondary outcomes were the discomfort scores of each
      IPREA item. IPREA was administered on the day of ICU discharge with a considered
      timeframe from the ICU admission until ICU discharge. RESULTS: During a 1-month
      assessment period, 398 and 360 patients were included in the experimental group
      and the control group, respectively. The difference (experimental minus control)
      of the overall discomfort score between groups was - 7.00 (95% CI - 9.89 to -
      4.11, p < 0.001). After adjustment (age, gender, ICU duration, mechanical
      ventilation duration, and type of admission), the program effect was still
      positive for the overall discomfort score (difference - 6.35, SE 1.23, p < 0.001)
      and for 12 out of 16 items. CONCLUSIONS: This tailored multicomponent program
      decreased self-perceived discomfort in adult critically ill patients. TRIAL
      REGISTRATION: Clinicaltrials.gov Identifier NCT02442934.

PMID- 29181562
TI  - Comments on 'Potential risk factors for birth fractures: a case-control study'.

PMID- 29181563
TI  - Final kissing balloon inflation for coronary bifurcation lesions treated with
      single-stent technique : A meta-analysis.
AB  - BACKGROUND: The efficacy of final kissing balloon (FKB) inflation in one-stent
      techniques for bifurcation lesions is controversial. The goal of the present
      study was to investigate the impact of FKB on long-term clinical outcomes in one
      stent strategies. METHODS: A literature search of the PubMed, Embase, and
      Cochrane Library databases was undertaken through August 2017. The primary
      outcome was major adverse cardiac events (MACE), defined as the composite of
      cardiac death, myocardial infarction, and target lesion revascularization.
      Overall hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated
      using the random-effects model. RESULTS: Ten studies comprising 7364 patients
      treated with a one-stent technique were included in the analysis. Overall, FKB
      did not demonstrate a significant reduction in MACE compared with non-FKB in both
      randomized trials (HR: 1.13; 95% CI: 0.65-1.98) and observational studies (HR:
      0.86; 95% CI: 0.61-1.20). The risk of cardiac death (HR: 0.89; 95% CI: 0.53
      1.49), myocardial infarction (HR: 0.76; 95% CI: 0.53-1.09), and target lesion
      revascularization (HR: 0.96; 95% CI: 0.74-1.23) was also similar in both groups.
      CONCLUSION: FKB may not be mandatory and a selective FKB strategy might be more
      justified in one-stent techniques for bifurcation lesions.

PMID- 29181564
TI  - A cadaver study into the number of fasciotomies required to decompress the
      anterior compartment in forearm compartment syndrome.
AB  - PURPOSE: There is no typical approach for decompression of forearm compartment
      syndrome, due to contradictory considerations regarding the characteristics of
      forearm anterior compartment deep fascia. The main purpose of this study was to
      determine how many fasciae should be opened to fully decompress the forearm
      anterior compartment. Further, the compliance of the deep anterior compartment
      was also investigated, to strengthen our results. METHODS: An experimental study
      of a laboratory model of acute forearm compartment syndrome was performed. A deep
      forearm injection of egg white was undertaken to create an acute forearm
      compartment syndrome in sixteen non-embalmed human forearms from six male and two
      female donors. The pressure in the superficial and deep anterior compartments was
      recorded four times, both before and after each fasciotomy and the compliance of
      the deep anterior compartment was calculated for each step. RESULTS: The first
      incision of the superficial lamina of the deep fascia was not sufficient to
      decrease the elevated compartment pressure in the superficial and deep anterior
      compartments. Whereas the pressures decreased to near-baseline levels, following
      the fasciotomy of the intermuscular septum observed posterior to the flexor carpi
      radialis. The last incision of the deep lamina of the deep anterior fascia had no
      noticeable impact. These observations supported the hypothesis of high compliance
      of the deep anterior compartment. CONCLUSION: Two successive incisions were
      necessary to decompress the anterior compartment: the incision of the superficial
      lamina of the deep fascia and the incision of the intermuscular septum.

PMID- 29181565
TI  - Postnatal myocardium remodelling generates inhomogeneity in the architecture of
      the ventricular mass.
AB  - BACKGROUND: The 3D architecture of the ventricular mass is poorly known, although
      in vivo imaging techniques show the physiological inhomogeneity of ventricular
      walls mechanics. Polarized light imaging makes it possible to quantitatively
      analyse the myosin filament orientation. AIMS: In this paper, we focus on the
      study the 3D architecture and regional isotropy of myocardial cells. METHODS:
      Twenty normal human hearts, 10 from the perinatal period and 10 from the post
      neonatal period were studied by polarized light microscopy. In each voxel of the
      ventricular mass (90 * 90 * 500 um) the principal orientation segment was
      automatically and unambiguously extracted as well as a regional isotropy index
      (regional orientation tensor of the voxel neighbourhood). RESULTS: During the
      first months of postnatal age, the median regional isotropy values decreased in
      the ventricular mesh. This global decrease was not homogeneous across the
      ventricular walls. From the perinatal to the neonatal period, this decrease was
      more marked in the inner two-third of the lateral left ventricular wall and in
      the right part of the interventricular septum. There was a progressive post
      neonatal appearance of a particularly inhomogeneous secondary arrangement of
      myocardial cells with alternation of thick low-RI and thin high-RI areas.
      CONCLUSIONS: This study has shown a postnatal change in ventricular myocardial
      architecture, which became more inhomogeneous. The cell rearrangements
      responsible for the inhomogeneity in ventricular myocardial architecture are
      revealed by a variation of the regional isotropy index. These major changes are
      probably an adaptive consequence of the major haemodynamic changes occurring
      after birth during the neonatal period that generates major parietal stress
      variations and parietal remodelling.

PMID- 29181567
TI  - From molecular engineering to process engineering: development of high-throughput
      screening methods in enzyme directed evolution.
AB  - With increasing concerns in sustainable development, biocatalysis has been
      recognized as a competitive alternative to traditional chemical routes in the
      past decades. As nature's biocatalysts, enzymes are able to catalyze a broad
      range of chemical transformations, not only with mild reaction conditions but
      also with high activity and selectivity. However, the insufficient activity or
      enantioselectivity of natural enzymes toward non-natural substrates limits their
      industrial application, while directed evolution provides a potent solution to
      this problem, thanks to its independence on detailed knowledge about the
      relationship between sequence, structure, and mechanism/function of the enzymes.
      A proper high-throughput screening (HTS) method is the key to successful and
      efficient directed evolution. In recent years, huge varieties of HTS methods have
      been developed for rapid evaluation of mutant libraries, ranging from in vitro
      screening to in vivo selection, from indicator addition to multi-enzyme system
      construction, and from plate screening to computation- or machine-assisted
      screening. Recently, there is a tendency to integrate directed evolution with
      metabolic engineering in biosynthesis, using metabolites as HTS indicators, which
      implies that directed evolution has transformed from molecular engineering to
      process engineering. This paper aims to provide an overview of HTS methods
      categorized based on the reaction principles or types by summarizing related
      studies published in recent years including the work from our group, to discuss
      assay design strategies and typical examples of HTS methods, and to share our
      understanding on HTS method development for directed evolution of enzymes
      involved in specific catalytic reactions or metabolic pathways.

PMID- 29181566
TI  - Could 68Ga-somatostatin analogues be an important alternative to 18F-DOPA PET/CT
      in pediatrics?

PMID- 29181568
TI  - Amexanthomycins A-J, pentangular polyphenols produced by Amycolatopsis
      mediterranei S699?rifA.
AB  - Ten new pentangular polyphenols, namely amexanthomycins A-J (1-10) were isolated
      from the strain Amycolatopsis mediterranei S699?rifA constructed by deleting the
      polyketide synthase genes responsible for the biosynthesis of rifamycins. Their
      structures were elucidated on the basis of 1D and 2D NMR spectroscopic data and
      high-resolution ESIMS. Amexanthomycins A-C (1-3) showed inhibitory activity
      against human DNA topoisomerases.

PMID- 29181569
TI  - Characterization of oligotrophic AnAOB culture: morphological, physiological, and
      ecological features.
AB  - Anaerobic ammonium oxidation (anammox) process is regarded as a promising
      nitrogen removal technology to treat ammonium wastewaters in a wide concentration
      range. Oligotrophic anaerobic ammonia oxidation bacteria (O-AnAOB) culture has
      been successfully achieved from a new anammox system to treat superlow ammonium
      concentration wastewaters. In this work, the O-AnAOB culture was compared with
      the eutrophic AnAOB (E-AnAOB) culture to reveal its physiological, morphological,
      and ecological features. Results showed that the specific anammox activity (SAA)
      of O-AnAOB culture was 0.07 kgN/(kgVSS.d) with the nitrogen removal rate (NRR) of
      0.20 kgN/ (m3 d) in the reactor, while the SAA of E-AnAOB culture was 2.11
      kgN/(kgVSS.d) with the NRR of 11.10 kgN/(m3 d). The hzs gene transcription levels
      (hzs-mRNA) of O-AnAOB and E-AnAOB cultures were 1.32 * 109 copies/gVSS and 1.51 *
      1010 copies/gVSS, respectively. Morphologically, the O-AnAOB culture took on the
      unique brown color rather than the typical red color of E-AnAOB. The O-AnAOB
      cells lived in a disperse pattern in the culture. The cells were seriously
      deformed with deep craters on the cell wall. The size of anammoxsome and
      paryphoplasm compartments inside the O-AnAOB cells was smaller than that inside
      the E-AnAOB cells. Ecologically, the O-AnAOB culture had special microbial
      community with a higher bacterial diversity than the E-AnAOB. The most dominant
      genera in O-AnAOB were Anaerolineaceae (33.7%, fermentative bacteria), Candidatus
      Kuenenia (17.4%, anammox bacteria), and Nitrospira (7.3%, nitrite oxidizing
      bacteria). This study provided an insight into the new anammox process for deep
      nitrogen removal from wastewaters.

PMID- 29181570
TI  - Improved production of dibenzocyclooctadiene lignans in the elicited microshoot
      cultures of Schisandra chinensis (Chinese magnolia vine).
AB  - Dibenzocyclooctadiene lignans are a specific group of secondary metabolites that
      occur solely in Schisandra chinensis. The aim of the presented work was to boost
      the accumulation of lignans in the agitated microshoot cultures of S. chinensis,
      using different elicitation schemes. The experiments included testing of various
      concentrations and supplementation times of cadmium chloride (CdCl2), chitosan
      (Ch), yeast extract (YeE), methyl jasmonate (MeJa), and permeabilizing agent
      dimethylsulfoxide (DMSO). After 30 days, the microshoots were harvested and
      evaluated for growth parameters and lignan content by LC-DAD method. The analyses
      showed enhanced production of lignans in the elicited S. chinensis microshoots,
      whereas the respective media samples contained only trace amounts of the examined
      compounds (< 5 mg/l). Elicitation with CdCl2 caused up to 2-fold increase in the
      total lignan content (max. ca. 730 mg/100 g DW after the addition of 1000 MUM
      CdCl2 on the tenth day). Experiments with chitosan resulted in up to 1.35-fold
      increase in lignan concentration (max. ca. 500 mg/100 g DW) after the
      supplementation with 50 mg/l on the first day and 200 mg/l on the tenth day. High
      improvement of lignan production was also recorded after YeE elicitation. After
      the elicitation with 5000 mg/l of YeE on the first day of the growth period, and
      with 1000 and 3000 mg/l on the 20th day, the lignan production increased to the
      same degree-about 1.8-fold. The supplementation with 1000 mg/l YeE on the 20th
      day of the growth cycle was chosen as the optimal elicitation scheme, for the
      microshoot cultures maintained in Plantform temporary immersion system-the total
      content of the estimated lignans was equal to 831.6 mg/100 g DW.

PMID- 29181571
TI  - Bisphosphonate drug holidays in postmenopausal osteoporosis: effect on clinical
      fracture risk. Response to comments by Bredemeier.

PMID- 29181572
TI  - Comments on Mignot et al.: bisphosphonate drug holidays in postmenopausal
      osteoporosis: effect on clinical fracture risk.

PMID- 29181573
TI  - Correction to: Determination of the absolute oral bioavailability of niraparib by
      simultaneous administration of a 14C-microtracer and therapeutic dose in cancer
      patients.
AB  - The article ''Determination of the absolute oral bioavailability of niraparib by
      simultaneous administration of a 14C-microtracer and therapeutic dose in cancer
      patients'', written by L. van Andel, H. Rosing, Z. Zhang, L. Hughes, V. Kansra,
      M. Sanghvi, M. M. Tibben, A. Gebretensae, J. H. M. Schellens and J. H. Beijnen,
      was originally published electronically on the publisher's internet portal
      (currently SpringerLink) on 17th October 2017 without open access.

PMID- 29181574
TI  - Letter to the Editor concerning "Risk factors for sciatica leading to
      hospitalization" by U. Euro et al. Eur Spine J (2017) doi:10.1007/s00586-017-5182
      8.

PMID- 29181575
TI  - Is L5-S1 motion segment different from the rest? A radiographic kinematic
      assessment of 72 patients with chronic low back pain.
AB  - PURPOSE: The relationship between biomechanical instability and degenerative
      changes in the lumbar spine in chronic low back pain (CLBP) patients remains
      controversial. The main objective of this retrospective radiographical study was
      to evaluate changes in kinematics at different lumbar levels (in particular the
      L5-S1 level) with progressive grades of disc degeneration and facet joint
      osteoarthritis in CLBP patients. METHODS: Using standing neutral and dynamic
      flexion/extension (Fx/Ex) radiographs of the lumbar spine, in vivo segmental
      kinematics at L1-L2 through L5-S1 were evaluated in 72 consecutive CLBP patients.
      Disc degeneration was quantified using changes in signal intensity and central
      disc height on mid-sagittal T2-weighted magnetic resonance (MR) scans.
      Additionally, the presence or absence of facet joint osteoarthritis was noted on
      T2-weighted axial MR scans. RESULTS: Disc degeneration and facet joint
      osteoarthritis occurred independent of each other at the L5-S1 level (p = 0.188),
      but an association was observed between the two at L4-L5 (p < 0.001) and L3-L4 (p
      < 0.05) levels. In the absence of facet joint osteoarthritis, the L5-S1 segment
      showed a greater range of motion (ROM) in Ex (3.3 degrees  +/- 3.6 degrees ) and
      a smaller ROM in Fx (0.6 degrees  +/- 4.2 degrees ) compared with the upper
      lumbar levels (p < 0.05), but the differences diminished in the presence of it.
      In the absence of facet joint osteoarthritis, no change in L5-S1 kinematics was
      observed with progressive disc degeneration, but in its presence, restabilisation
      of the L5-S1 segment was observed between mild and severe disc degeneration
      states. CONCLUSION: The L5-S1 motion segment exhibited unique degenerative and
      kinematic characteristics compared with the upper lumbar motion segments. Disc
      degeneration and facet joint osteoarthritis occurred independent of each other at
      the L5-S1 level, but not at the other lumbar levels. Severe disc degeneration in
      the presence of facet joint osteoarthritis biomechanically restabilised the L5-S1
      motion segment.

PMID- 29181577
TI  - Correction to: Phytophagy of omnivorous predator Macrolophus pygmaeus affects
      performance of herbivores through induced plant defences.
AB  - Unfortunately, the citation of one of the papers was published erroneously in the
      original version and corrected here by this Erratum. The original article was
      corrected.

PMID- 29181576
TI  - Expression profile of microRNA-146a along HPV-induced multistep carcinogenesis: a
      study in HPV16 transgenic mice.
AB  - PURPOSE: Persistent human papillomavirus (HPV) infection is associated with the
      development of certain types of cancer and the dysregulation of microRNAs has
      been implicated in HPV-associated carcinogenesis. This is the case of microRNA
      146a (miR-146a), which is thought to regulate tumor-associated inflammation. We
      sought to investigate the expression levels of miR-146a during HPV16-mediated
      carcinogenesis using skin samples from K14-HPV16 transgenic mice which develop
      the consecutive phases of the carcinogenesis process. METHODS: Female transgenic
      (HPV+/-) and wild-type (HPV-/-) mice were sacrificed at 24-26 weeks-old or 28-30
      weeks-old. Chest and ear skin samples from HPV+/- and HPV-/- mice were
      histologically classified and used for microRNA extraction and quantification by
      qPCR. RESULTS: Chest skin samples from 24 to 26 weeks-old HPV+/- mice presented
      diffuse epidermal hyperplasia and only 22.5% showed multifocal dysplasia, while
      at 28-30 weeks-old all (100.0%) HPV+/- animals showed epidermal dysplasia. All
      HPV+/- ear skin samples showed carcinoma in situ (CIS). MiR-146a expression
      levels were higher in HPV+/- compared to HPV-/- mice (p = 0.006). There was also
      an increase in miR-146a expression in dysplastic skin lesions compared with
      hyperplasic lesions (p = 0.011). Samples showing CIS had a significant decrease
      in miR-146a expression when compared to samples showing epidermal hyperplasia (p
      = 0.018) and epidermal dysplasia (p = 0.009). CONCLUSIONS: These results suggest
      that HPV16 induces the overexpression of miR-146a in the initial stages of
      carcinogenesis (hyperplasia and dysplasia), whereas decreases its expression at
      later stages (CIS). Taken together, these data implicate and suggest different
      roles of miR-146a in HPV-mediated carcinogenesis.

PMID- 29181579
TI  - Mediterranean diet: fresh herbs and fresh vegetables decrease the risk of
      Androgenetic Alopecia in males.
AB  - It is well established that Androgenetic Alopecia (AGA) occurs in genetically
      predisposed individuals but little is known of its non-genetic risk factors. The
      aim of the study was to investigate the role of the Mediterranean diet in
      determining the risk of AGA. A hospital-based case-control study was conducted in
      the outpatient clinics of the hospital "Istituto Dermopatico dell'Immacolata,
      Rome, Italy". We included 104 males and 108 controls not affected by AGA.
      Controls were frequency matched to cases. Information on socio-demographic
      characteristics, medical history, smoking and diet were collected for all
      patients. Logistic regression was used to estimate odds ratio and 95% confidence
      intervals. After controlling for age, education, body mass index and family
      history of AGA, protective effects for AGA were found for high consumption (>= 3
      times weekly) of raw vegetables (OR 0.43; 95% CI 0.21-0.89) and high consumption
      of fresh herbs (3 or more regularly) (OR 0.44; 95% CI 0.22-0.87). We suggest that
      some foods of the Mediterranean diet, say fresh herbs and salad, may reduce the
      risk of AGA onset.

PMID- 29181578
TI  - Practical recommendations for fertility preservation in women by the FertiPROTEKT
      network. Part II: fertility preservation techniques.
AB  - PURPOSE: In addition to guidelines focusing on scientific evidence, practical
      recommendations on fertility preservation are also needed. METHODS: A selective
      literature search was performed based on the clinical and scientific experience
      of the authors. This article (Part II) focuses on fertility preservation
      techniques. Part I, also published in this journal, provides information on
      disease prognosis, disease-specific therapy, and risks for loss of fertility.
      RESULTS: Ovarian stimulation including double stimulation and freezing of oocytes
      is the best-established therapy providing live birth chances in women < 35 years
      with high ovarian reserve of around 30-40%. Ovarian tissue freezing is especially
      useful in young women with good ovarian, if spontaneous conception is favoured
      and if < 1 week until chemotherapy is provided. Data on success rates are still
      limited, but this further evolving technique will possibly reach similar success
      rates as ovarian stimulation. GnRH agonists seem to reduce the risk of premature
      ovarian failure up to 50%; however, the effect is possibly not long-lasting.
      Ovarian transposition can easily be combined with freezing of ovarian tissue and
      is the preferred technique before pelvic radiotherapy. Other techniques, such as
      in vitro maturation, are limited to women with high ovarian reserve and remain
      less effective. In addition, procedures such as in vitro growth of follicles,
      etc. are still experimental. CONCLUSIONS: Fertility preservation in women
      provides realistic chances of becoming pregnant. The choice of technique needs to
      be based on the time required, the woman's age, its risks and efficacy, and the
      individual preference of the patient.

PMID- 29181581
TI  - Evaluation of femoral head viability via bone scintigraphy in the postoperative
      pediatric patient.
AB  - BACKGROUND: Evaluating postoperative patients with hardware is challenging
      following surgical intervention for hip maladies such as femoral neck fractures
      and slipped capital femoral epiphysis (SCFE). These children are at increased
      risk of developing avascular necrosis, and imaging may be requested to confirm or
      exclude this diagnosis. Children with Legg-Calve-Perthes disease can be monitored
      for restoration of blood flow to the capital femoral epiphysis to guide
      management and help with prognosis. Although MRI is sensitive for detecting early
      avascular necrosis, the presence of hardware degrades image quality. OBJECTIVE:
      This report examines the utility of bone scans for evaluating femoral head
      perfusion in children who have undergone surgery for femoral neck fractures, SCFE
      or Legg-Calve-Perthes disease. MATERIALS AND METHODS: A retrospective review of
      20 patients (22 scans) after fixation for femoral neck fracture, SCFE or Legg
      Calve-Perthes disease from 2012 to 2015 was performed. The bone scan findings
      were correlated with the intraoperative findings or clinical follow-up. RESULTS:
      Twenty-one of the 22 (95%) bone scans in 19 of the 20 (95%) patients demonstrated
      findings consistent with clinical outcomes and/or the intraoperative appearance
      of the femoral head. Four of 20 patients (20%) had bone scan features of
      avascular necrosis, defined as "absent" or "moderately diminished" femoral head
      activity, which were confirmed intraoperatively and resulted in poor outcomes.
      CONCLUSION: Radionuclide imaging of hips in the postoperative setting is a
      valuable modality for assessing the risk of avascular necrosis, a complication of
      femoral neck fractures and SCFE and for evaluating the restoration of flow to the
      capital femoral epiphyses of children with Legg-Calve-Perthes disease.

PMID- 29181580
TI  - Ionizing radiation from computed tomography versus anesthesia for magnetic
      resonance imaging in infants and children: patient safety considerations.
AB  - In the context of health care, risk assessment is the identification, evaluation
      and estimation of risk related to a particular clinical situation or intervention
      compared to accepted medical practice standards. The goal of risk assessment is
      to determine an acceptable level of risk for a given clinical treatment or
      intervention in association with the provided clinical circumstances for a
      patient or group of patients. In spite of the inherent challenges related to risk
      assessment in pediatric cross-sectional imaging, the potential risks of ionizing
      radiation and sedation/anesthesia in the pediatric population are thought to be
      quite small. Nevertheless both issues continue to be topics of discussion
      concerning risk and generate significant anxiety and concern for patients,
      parents and practicing pediatricians. Recent advances in CT technology allow for
      more rapid imaging with substantially lower radiation exposures, obviating the
      need for anesthesia for many indications and potentially mitigating concerns
      related to radiation exposure. In this review, we compare and contrast the
      potential risks of CT without anesthesia against the potential risks of MRI with
      anesthesia, and discuss the implications of this analysis on exam selection,
      providing specific examples related to neuroblastoma surveillance imaging.

PMID- 29181582
TI  - Contrast-enhanced voiding urosonography (ceVUS) with the intravesical
      administration of the ultrasound contrast agent OptisonTM for vesicoureteral
      reflux detection in children: a prospective clinical trial.
AB  - BACKGROUND: Contrast-enhanced voiding urosonography (ceVUS) is widely used
      outside the United States to diagnose vesicoureteral reflux (VUR) in children and
      is highly sensitive while avoiding exposure to ionizing radiation. At the onset
      of this study, two ultrasound (US) contrast agents were available in the United
      States. Pediatric safety data for intravenous administration was published for
      one, OptisonTM. OBJECTIVE: This study aimed to evaluate the diagnostic
      performance and safety of ceVUS using OptisonTM and compare its diagnostic
      efficacy with voiding cystourethrogram (VCUG) for VUR detection and grading in
      children. MATERIALS AND METHODS: The United States Food and Drug Administration
      and institutional Investigational New Drug authorizations were obtained to
      conduct a prospective comparative study of ceVUS with OptisonTM and VCUG. CeVUS
      was performed with intravesical administration of 0.2% OptisonTM/normal saline
      solution. A standard VCUG followed. Safety assessment included physical
      examination, and heart rate, pulse oximetry and adverse reactions monitoring
      before, during and immediately after the examinations. A follow-up questionnaire
      was completed by telephone 48-h after the studies. RESULTS: Sixty-two
      pelviureteric units were studied in 30 patients with a mean age of 3.5 years
      (range: 0.1-17 years) including 21 girls and 9 boys. No severe adverse events
      occurred. All patients had normal heart rate and blood oxygenation saturation
      prior to, during and after the studies. At the 48-h follow-up, one patient (3.3%)
      reported transient dysuria. Taking the VCUG as the reference standard, ceVUS had
      a sensitivity of 91.7% (95%; confidence interval [CI]: 61.5%-99.8%) and
      specificity of 98% (95%; CI: 89.4%-99.9%). The concordance between ceVUS and VCUG
      for VUR detection and grading was 84.3% and 81.8%, respectively. VUR grades were
      discrepant in 4/11 refluxing pelviureteric units, with VCUG upgrading VUR in 2.
      CONCLUSION: Detection of VUR with OptisonTM ceVUS was comparable to VCUG without
      exposure to ionizing radiation. CeVUS with OptisonTM is a well-tolerated
      diagnostic procedure with a favorable safety profile.

PMID- 29181583
TI  - Individual differences in emotion processing: how similar are diffusion model
      parameters across tasks?
AB  - The goal of this study was to replicate findings of diffusion model parameters
      capturing emotion effects in a lexical decision task and investigating whether
      these findings extend to other tasks of implicit emotion processing.
      Additionally, we were interested in the stability of diffusion model parameters
      across emotional stimuli and tasks for individual subjects. Responses to words in
      a lexical decision task were compared with responses to faces in a gender
      categorization task for stimuli of the emotion categories: happy, neutral and
      fear. Main effects of emotion as well as stability of emerging response style
      patterns as evident in diffusion model parameters across these tasks were
      analyzed. Based on earlier findings, drift rates were assumed to be more similar
      in response to stimuli of the same emotion category compared to stimuli of a
      different emotion category. Results showed that emotion effects of the tasks
      differed with a processing advantage for happy followed by neutral and fear
      related words in the lexical decision task and a processing advantage for neutral
      followed by happy and fearful faces in the gender categorization task. Both
      emotion effects were captured in estimated drift rate parameters-and in case of
      the lexical decision task also in the non-decision time parameters. A principal
      component analysis showed that contrary to our hypothesis drift rates were more
      similar within a specific task context than within a specific emotion category.
      Individual response patterns of subjects across tasks were evident in significant
      correlations regarding diffusion model parameters including response styles, non
      decision times and information accumulation.

PMID- 29181584
TI  - Testing a potential alternative to traditional identification procedures:
      Reaction time-based concealed information test does not work for lineups with
      cooperative witnesses.
AB  - Direct eyewitness identification is widely used, but prone to error. We tested
      the validity of indirect eyewitness identification decisions using the reaction
      time-based concealed information test (CIT) for assessing cooperative
      eyewitnesses' face memory as an alternative to traditional lineup procedures. In
      a series of five experiments, a total of 401 mock eyewitnesses watched one of 11
      different stimulus events that depicted a breach of law. Eyewitness
      identifications in the CIT were derived from longer reaction times as compared to
      well-matched foil faces not encountered before. Across the five experiments, the
      weighted mean effect size d was 0.14 (95% CI 0.08-0.19). The reaction time-based
      CIT seems unsuited for testing cooperative eyewitnesses' memory for faces. The
      careful matching of the faces required for a fair lineup or the lack of intent to
      deceive may have hampered the diagnosticity of the reaction time-based CIT.

PMID- 29181585
TI  - [Rheumatism and the spine].

PMID- 29181586
TI  - [Indications for joint replacement : Total hip arthroplasty].
AB  - Total hip arthroplasty (THA) is a very successful and effective orthopedic
      operation with very good immediate as well as long-term results to alleviate pain
      and improve health-related quality of life. A THA is indicated in end-stage hip
      osteoarthritis with a high degree of persistent suffering when conservative
      treatment has failed and in patients who wish a THA. This statement is generally
      valid for patients where the medical history, clinical examination and
      radiographic findings are conclusive, the pressure of suffering and the
      expectations are realistic. The timing of THA is based on the patient's
      discomfort. The treatment of these patients should include an interdisciplinary
      approach and the main goal is to improve the quality of life. Patients will learn
      to have reasonable expectations and should be well informed about the risks and
      benefits of THA. Realistic patient expectations seem to be a predictive factor
      for a good subjective outcome after THA.

PMID- 29181587
TI  - Diagnostic accuracy of low and high tube voltage coronary CT angiography using an
      X-ray tube potential-tailored contrast medium injection protocol.
AB  - OBJECTIVES: To compare the diagnostic accuracy between low-kilovolt peak (kVp)
      (<= 100) and high-kVp (> 100) third-generation dual-source coronary CT
      angiography (CCTA) using a kVp-tailored contrast media injection protocol.
      METHODS: One hundred twenty patients (mean age = 62.6 years, BMI = 29.0 kg/m2)
      who underwent catheter angiography and CCTA with automated kVp selection were
      separated into two cohorts (each n = 60, mean kVp = 84 and 117). Contrast media
      dose was tailored to the kVp level: 70 = 40 ml, 80 = 50 ml, 90 = 60 ml, 100 = 70
      ml, 110 = 80 ml, and 120 = 90 ml. Contrast-to-noise ratio (CNR) was measured. Two
      observers evaluated image quality and the presence of significant coronary
      stenosis (> 50% luminal narrowing). RESULTS: Diagnostic accuracy
      (sensitivity/specificity) with <= 100 vs. > 100 kVp CCTA was comparable: per
      patient = 93.9/92.6% vs. 90.9/92.6%, per vessel = 91.5/97.8% vs. 94.0/96.8%, and
      per segment = 90.0/96.7% vs. 90.7/95.2% (all P > 0.64). CNR was similar (P >
      0.18) in the low-kVp vs. high-kVp group (12.0 vs. 11.1), as ws subjective image
      quality (P = 0.38). Contrast media requirements were reduced by 38.1% in the low-
      vs. high-kVp cohort (53.6 vs. 86.6 ml, P < 0.001) and radiation dose by 59.6%
      (4.3 vs. 10.6 mSv, P < 0.001). CONCLUSIONS: Automated tube voltage selection with
      a tailored contrast media injection protocol allows CCTA to be performed at <=
      100 kVp with substantial dose reductions and equivalent diagnostic accuracy for
      coronary stenosis detection compared to acquisitions at > 100 kVp. KEY POINTS: *
      Low-kVp coronary CT angiography (CCTA) enables reduced contrast and radiation
      dose. * Diagnostic accuracy is comparable between <= 100 and > 100 kVp CCTA. *
      Image quality is similar for low- and high-kVp CCTA. * Low-kVp image acquisition
      is facilitated by automated tube voltage selection. * Tailoring contrast
      injection protocols to the automatically selected kVp-level is feasible.

PMID- 29181588
TI  - High doses of folic acid in the periconceptional period and risk of low weight
      for gestational age at birth in a population based cohort study.
AB  - PURPOSE: We investigated the association between maternal use of folic acid (FA)
      during pregnancy and child anthropometric measures at birth. METHODS: We included
      2302 mother-child pairs from a population-based birth cohort in Spain (INMA
      Project). FA dosages at first and third trimester of pregnancy were assessed
      using a specific battery questionnaire and were categorized in non-user, < 1000,
      1000-4999, and >= 5000 ug/day. Anthropometric measures at birth (weight in grams,
      length and head circumference in centimetres) were obtained from medical records.
      Small for gestational age according to weight (SGA-w), length (SGA-l) and head
      circumference (SGA-hc) were defined using the 10th percentile based on Spanish
      standardized growth reference charts. Multiple linear and logistic regression
      analyses were used to explore the association between FA dosages in different
      stages of pregnancy and child anthropometric measures at birth. RESULTS: In the
      multiple linear regression analysis, we found a tendency for a negative
      association between the use of high dosages of FA (>= 5000 ug/day) in the
      periconceptional period of pregnancy and weight at birth compared to mothers who
      were non-users of FA (beta = - 73.83; 95% CI - 151.71, 4.06). In the multiple
      logistic regression, a greater risk of SGA-w was also evident among children
      whose mothers took FA dosages of 1000-4999 (OR = 2.21; 95% CI 1.17, 4.19) and of
      >= 5000 ug/day (OR = 2.32; 95% CI 1.06, 5.08) compared to mothers non-users of FA
      in the periconceptional period of pregnancy. CONCLUSION: Our findings suggest
      that a high dosage of FA (>= 1000 ug/day) may be associated with an increased
      risk of SGA-w at birth.

PMID- 29181589
TI  - Disentangling brain activity related to the processing of emotional visual
      information and emotional arousal.
AB  - Processing of emotional visual information engages cognitive functions and
      induces arousal. We aimed to examine the modulatory role of emotional valence on
      brain activations linked to the processing of visual information and those linked
      to arousal. Participants were scanned and their pupil size was measured while
      viewing negative and neutral images. The visual noise was added to the images in
      various proportions to parametrically manipulate the amount of visual
      information. Pupil size was used as an index of physiological arousal. We show
      that arousal induced by the negative images, as compared to the neutral ones, is
      primarily related to greater amygdala activity while increasing visibility of
      negative content to enhanced activity in the lateral occipital complex (LOC). We
      argue that more intense visual processing of negative scenes can occur
      irrespective of the level of arousal. It may suggest that higher areas of the
      visual stream are fine-tuned to process emotionally relevant objects. Both
      arousal and processing of emotional visual information modulated activity within
      the ventromedial prefrontal cortex (vmPFC). Overlapping activations within the
      vmPFC may reflect the integration of these aspects of emotional processing.
      Additionally, we show that emotionally-evoked pupil dilations are related to
      activations in the amygdala, vmPFC, and LOC.

PMID- 29181590
TI  - Using Telemedicine for Tuberculosis Care Management: a Three County Inter
      Municipal Approach.

PMID- 29181591
TI  - Post-zygotic genomic changes in glutamate and dopamine pathway genes may explain
      discordance of monozygotic twins for schizophrenia.
AB  - BACKGROUND: Monozygotic twins are valuable in assessing the genetic vs
      environmental contribution to diseases. In the era of complete genome sequences,
      they allow identification of mutational mechanisms and specific genes and
      pathways that offer predisposition to the development of complex diseases
      including schizophrenia. METHODS: We sequenced the complete genomes of two pairs
      of monozygotic twins discordant for schizophrenia (MZD), including one
      representing a family tetrad. The family specific complete sequences have allowed
      identification of post zygotic mutations between MZD genomes. It allows
      identification of affected genes including relevant network and pathways that may
      account for the diseased state in pair specific patient. RESULTS: We found
      multiple twin specific sequence differences between co-twins that included small
      nucleotides [single nucleotide variants (SNV), small indels and block
      substitutions], copy number variations (CNVs) and structural variations. The
      genes affected by these changes belonged to a number of canonical pathways, the
      most prominent ones are implicated in schizophrenia and related disorders.
      Although these changes were found in both twins, they were more frequent in the
      affected twin in both pairs. Two specific pathway defects, glutamate receptor
      signaling and dopamine feedback in cAMP signaling pathways, were uniquely
      affected in the two patients representing two unrelated families. CONCLUSIONS: We
      have identified genome-wide post zygotic mutations in two MZD pairs affected with
      schizophrenia. It has allowed us to use the threshold model and propose the most
      likely cause of this disease in the two patients studied. The results support the
      proposition that each schizophrenia patient may be unique and heterogeneous
      somatic de novo events may contribute to schizophrenia threshold and discordance
      of the disease in monozygotic twins.

PMID- 29181592
TI  - Selection and Qualification of Simplified QSP Models When Using Model Order
      Reduction Techniques.
AB  - Quantitative systems pharmacology (QSP) models are increasingly used in drug
      development to provide a deep understanding of the mechanism of action of drugs
      and to identify appropriate disease targets. Such models are, however, not
      suitable for estimation purposes due to their high dimensionality. Based on any
      desired and specific input-output relationship, the system may be reduced to a
      model with fewer states and parameters. However, any simplification process will
      be a trade-off between model performance and complexity. In this study, we
      develop a weighted composite criterion which brings together the opposing indices
      of performance and dimensionality. The weighting factor can be determined by
      qualification of the simplified model based on a visual predictive check (VPC)
      using the precision of each parameter. The weighted criterion and model
      qualification techniques were illustrated with three examples: a simple
      compartmental pharmacokinetic model, a physiologically based pharmacokinetic
      (PBPK) example, and a semimechanistic model for bone mineral density. When
      considering the PBPK example, this automated search identified the same reduced
      model which had been detected in a previous report, as well as a simpler model
      which had not been previously identified. The simpler bone mineral density model
      provided an adequate description of the response even after 1 year from the
      initiation of treatment. The proposed criterion together with a VPC provides a
      natural way for model order reduction that can be fully automated and applied to
      multiscale models.

PMID- 29181593
TI  - Real Patient and its Virtual Twin: Application of Quantitative Systems Toxicology
      Modelling in the Cardiac Safety Assessment of Citalopram.
AB  - A quantitative systems toxicology (QST) model for citalopram was established to
      simulate, in silico, a 'virtual twin' of a real patient to predict the occurrence
      of cardiotoxic events previously reported in patients under various clinical
      conditions. The QST model considers the effects of citalopram and its most
      notable electrophysiologically active primary (desmethylcitalopram) and secondary
      (didesmethylcitalopram) metabolites, on cardiac electrophysiology. The in vitro
      cardiac ion channel current inhibition data was coupled with the biophysically
      detailed model of human cardiac electrophysiology to investigate the impact of
      (i) the inhibition of multiple ion currents (IKr, IKs, ICaL); (ii) the inclusion
      of metabolites in the QST model; and (iii) unbound or total plasma as the
      operating drug concentration, in predicting clinically observed QT prolongation.
      The inclusion of multiple ion channel current inhibition and metabolites in the
      simulation with unbound plasma citalopram concentration provided the lowest
      prediction error. The predictive performance of the model was verified with three
      additional therapeutic and supra-therapeutic drug exposure clinical cases. The
      results indicate that considering only the hERG ion channel inhibition of only
      the parent drug is potentially misleading, and the inclusion of active metabolite
      data and the influence of other ion channel currents should be considered to
      improve the prediction of potential cardiac toxicity. Mechanistic modelling can
      help bridge the gaps existing in the quantitative translation from preclinical
      cardiac safety assessment to clinical toxicology. Moreover, this study shows that
      the QST models, in combination with appropriate drug and systems parameters, can
      pave the way towards personalised safety assessment.

PMID- 29181594
TI  - Determination of lesinurad in rat plasma by a UHPLC-MS/MS assay.
AB  - Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has
      been approved by the US Food and Drug Administration for combination therapy with
      a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with
      refractory gout. In the present study, a sensitive and specific ultra high
      performance liquid chromatography with tandem mass spectrometry assay was
      established and verified for the determination of lesinurad in rat plasma and was
      described in details for the first time. Chromatographic separation of lesinurad
      and diazepam (internal standard, IS) was performed on a Rapid Resolution HT C18
      column (3.0 * 100 mm, 1.8 um) using methanol-water (70:30, v/v) as the mobile
      phase at a flow rate of 0.3 mL/min. Lesinurad and IS were extracted from plasma
      by liquid-liquid extraction using ethyl acetate. The mass spectrometric detection
      was carried out using an electrospray ionization source in positive mode.
      Multiple reaction monitoring was used for quantification of the precursor to
      product ion at m/z 405.6 -> 220.9 for lesinurad and m/z 285.1 -> 192.8 for IS.
      The assay was well validated for selectivity, accuracy, precision, recovery,
      linearity, matrix effects, and stability. The verified method was applied to
      obtain the pharmacokinetic parameters and concentration-time profiles for
      lesinurad after oral/intravenous administration in rats. The study might provide
      an important reference and a necessary complement for the qualitative and
      quantitative evaluation of lesinurad.

PMID- 29181595
TI  - Integration of Waste Valorization for Sustainable Production of Chemicals and
      Materials via Algal Cultivation.
AB  - Managing waste is an increasing problem globally. Microalgae have the potential
      to help remove contaminants from a range of waste streams and convert them into
      useful biomass. This article presents a critical review of recent technological
      developments in the production of chemicals and other materials from microalgae
      grown using different types of waste. A range of novel approaches are examined
      for efficiently capturing CO2 in flue gas via photosynthetic microalgal
      cultivation. Strategies for using microalgae to assimilate nitrogen, organic
      carbon, phosphorus, and metal ions from wastewater are considered in relation to
      modes of production. Generally, more economical open cultivation systems such as
      raceway ponds are better suited for waste conversion than more expensive closed
      photobioreactor systems, which might have use for higher-value products. The
      effect of cultivation methods and the properties of the waste streams on the
      composition the microalgal biomass is discussed relative to its utilization.
      Possibilities include the production of biodiesel via lipid extraction, biocrude
      from hydrothermal liquefaction, and bioethanol or biogas from microbial
      conversion. Microalgal biomass produced from wastes may also find use in higher
      value applications including protein feeds or for the production of bioactive
      compounds such as astaxanthin or omega-3 fatty acids. However, for some waste
      streams, further consideration of how to manage potential microbial and chemical
      contaminants is needed for food or health applications. The use of microalgae for
      waste valorization holds promise. Widespread implementation of the available
      technologies will likely follow from further improvements to reduce costs, as
      well as the increasing pressure to effectively manage waste.

PMID- 29181597
TI  - From lighthouse to hothouse: hospital hygiene, antibiotics and the evolution of
      infectious disease, 1950-1990.
AB  - Upon entering clinical medicine in the 1940s, antibiotic therapy seemed to
      complete a transformation of hospitals that originated in the late nineteenth
      century. Former death sinks had become harbingers of therapeutic progress. Yet
      this triumph was short-lived. The arrival of pathologies caused by resistant
      bacteria, and of nosocomial infections whose spread was helped by antibiotic
      therapies, seemed to be intimately related to modern anti-infective therapy. The
      place where such problems culminated were hospitals, which increasingly appeared
      as dangerous environments where attempts to combat infectious diseases had
      instead created hothouses of disease evolution. This paper will focus on one
      aspect of that history. It caused clinical medicine and hospital hygiene in
      particular to pay attention to a dimension of infectious disease it had
      previously paid little attention to thus far: The evolution of infectious disease
      previously a matter of mostly theoretical interest-came to be useful in
      explaining many phenomena observed. This did not turn hospital hygienists into
      geneticists, though it did give them an awareness that the evolution of
      infectious disease in a broad sense was something that did matter to them. The
      paper advances its argument by looking at three phases: The growing awareness of
      the hospital as a dangerous environment in the 1950s, comprehensive attempts at
      improving antibiotic therapy and hospital hygiene that followed from the 1960s
      and lastly the framing of such challenges as risk factors from the 1970s. In
      conclusion, I will argue that hospital hygiene, being inspired in particular by
      epidemiology and risk factor analysis, discussed its own specific version of
      disease emergence and therefore contributed to the 1980s debates around such
      topics. Being loosely connected to more specialized studies, it consisted of a re
      interpretation of infectious disease centred around the temporality of such
      phenomena as they were encountered in day-to-day dealings of clinical wards.

PMID- 29181596
TI  - Recent Developments in Single-Walled Carbon Nanotube Thin Films Fabricated by Dry
      Floating Catalyst Chemical Vapor Deposition.
AB  - Transparent conducting films (TCFs) are critical components of many
      optoelectronic devices that pervade modern technology. Due to their excellent
      optoelectronic properties and flexibility, single-walled carbon nanotube (SWNT)
      films are regarded as an important alternative to doped metal oxides or brittle
      and expensive ceramic materials. Compared with liquid-phase processing, the dry
      floating catalyst chemical vapor deposition (FCCVD) method without dispersion of
      carbon nanotubes (CNTs) in solution is more direct and simpler. By overcoming the
      tradeoff between CNT length and solubility during film fabrication, the dry FCCVD
      method enables production of films that contain longer CNTs and offer excellent
      optoelectronic properties. This review focuses on fabrication of SWNT films using
      the dry FCCVD method, covering SWNT synthesis, thin-film fabrication and
      performance regulation, the morphology of SWNTs and bundles, transparency and
      conductivity characteristics, random bundle films, patterned films, individual
      CNT networks, and various applications, especially as TCFs in touch displays.
      Films based on SWNTs produced by the dry FCCVD method are already commercially
      available for application in touch display devices. Further research on the dry
      FCCVD method could advance development of not only industrial applications of
      CNTs but also the fundamental science of related nanostructured materials and
      nanodevices.

PMID- 29181598
TI  - History as a biomedical matter: recent reassessments of the first cases of
      Alzheimer's disease.
AB  - This paper examines medical scientists' accounts of their rediscoveries and
      reassessments of old materials. It looks at how historical patient files and
      brain samples of the first cases of Alzheimer's disease became reused as
      scientific objects of inquiry in the 1990s, when a genetic neuropathologist from
      Munich and a psychiatrist from Frankfurt lead searches for left-overs of
      Alzheimer's 'founder cases' from the 1900s. How and why did these researchers use
      historical methods, materials and narratives, and why did the biomedical
      community cherish their findings as valuable scientific facts about Alzheimer's
      disease? The paper approaches these questions by analysing how researchers
      conceptualised 'history' while backtracking and reassessing clinical and
      histological materials from the past. It elucidates six ways of conceptualising
      history as a biomedical matter: (1) scientific assessments of the past, i.e.
      natural scientific understandings of 'historical facts'; (2) history in
      biomedicine, e.g. uses of old histological collections in present day brain
      banks; (3) provenance research, e.g. applying historical methods to ensure the
      authenticity of brain samples; (4) technical biomedical history, e.g. reproducing
      original staining techniques to identify how old histological slides were made;
      (5) founding traditions, i.e. references to historical objects and persons within
      founding stories of scientific communities; and (6) priority debates, e.g.
      evaluating the role particular persons played in the discovery of a disease such
      as Alzheimer's. Against this background, the paper concludes with how the various
      ways of using and understanding 'history' were put forward to re-present historic
      cases as 'proto-types' for studying Alzheimer's disease in the present.

PMID- 29181599
TI  - Bioconversion of farnesol and 1,4-dihydroxy-2-naphthoate to menaquinone by an
      immobilized whole-cell biocatalyst using engineered Elizabethkingia
      meningoseptica.
AB  - Menaquinone (MK) has important applications in the pharmaceutical and food
      industries. To increase the production rate (QP) of MK-4, we developed a
      straightforward biotransformation method for MK-4 synthesis directly from its
      precursors 1,4-dihydroxy-2-naphthoate (DHNA) and farnesol using whole cells of
      genetically engineered Elizabethkingia meningoseptica. Results showed that MK-4
      can be produced directly from farnesol and DHNA using both free and immobilized
      FM-D198 cells. MK-4 yield peaked at 29.85 +/- 0.36 mg/L in the organic phase and
      24.08 +/- 0.33 mg/g DCW after 12 h of bioconversion using free cells in a two
      phase conversion system. MK-4 yield reached 26.34 +/- 1.35 mg/L and 17.44 +/-
      1.05 mg/g DCW after 8 h using immobilized cells. Although this yield was lower
      than that using free cells, immobilized cells can be re-used for MK-4 production
      via repeated-batch culture. After ten batch cultures, efficient MK-4 production
      was maintained at a yield of more than 20 mg/L. After optimizing the catalysis
      system, the MK-4 yield reached 26.91 +/- 1.27 mg/L using the immobilized cells
      and had molar conversion rates of 58.56 and 76.90% for DHNA and farnesol,
      respectively.

PMID- 29181600
TI  - Strategies for improving production performance of probiotic Pediococcus
      acidilactici viable cell by overcoming lactic acid inhibition.
AB  - Lactic acid bacteria are industrially important microorganisms recognized for
      fermentative ability mostly in their probiotic benefits as well as lactic acid
      production for various applications. Fermentation conditions such as
      concentration of initial glucose in the culture, concentration of lactic acid
      accumulated in the culture, types of pH control strategy, types of aeration mode
      and different agitation speed had influenced the cultivation performance of batch
      fermentation of Pediococcus acidilactici. The maximum viable cell concentration
      obtained in constant fed-batch fermentation at a feeding rate of 0.015 L/h was
      6.1 times higher with 1.6 times reduction in lactic acid accumulation compared to
      batch fermentation. Anion exchange resin, IRA 67 was found to have the highest
      selectivity towards lactic acid compared to other components studied. Fed-batch
      fermentation of P. acidilactici coupled with lactic acid removal system using IRA
      67 resin showed 55.5 and 9.1 times of improvement in maximum viable cell
      concentration compared to fermentation without resin for batch and fed-batch mode
      respectively. The improvement of the P. acidilactici growth in the constant fed
      batch fermentation indicated the use of minimal and simple process control
      equipment is an effective approach for reducing by-product inhibition. Further
      improvement in the cultivation performance of P. acidilactici in fed-bath
      fermentation with in situ addition of anion-exchange resin significantly helped
      to enhance the growth of P. acidilactici by reducing the inhibitory effect of
      lactic acid and thus increasing probiotic production.

PMID- 29181601
TI  - Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management
      Considerations.
AB  - PURPOSE OF REVIEW: Purpose of review Acute flaccid myelitis is a polio-like
      illness defined by the acute onset of flaccid paralysis in the setting spinal MRI
      demonstrating a longitudinal lesion in the gray matter of the cord. This paper
      aims to review the current state of knowledge and key clinical points for the
      diagnosis and management of acute flaccid myelitis. RECENT FINDINGS: Recent
      findings There were clusters of AFM noted in California and Colorado in 2014,
      with additional cases across the USA that year, and another spike in cases in
      2016. Patients have been managed with classic treatments for transverse myelitis,
      but in general without benefit, although some colleagues have noted anecdotal
      improvement in individual patients. Our current practice at the Children's
      Hospital of Philadelphia is to initiate therapy with intravenous immunoglobulin
      (IVIG) upon recognition of acute flaccid myelitis in hopes of boosting humoral
      immunity, and to provide an emphasis on rehabilitation services, including
      physical and occupational therapy. There is some data that suggests a connection
      to the virus enterovirus D68 (EV D68), but there has been no definitive link.
      Publications regarding longer-term outcomes in these patients are early in
      development and, thus far, only provide data for 6 to 12 months from onset.
      Summary AFM is a serious illness with long-term consequences, and we have much to
      learn. Key areas in need of further investigation involve etiology, host
      susceptibilities, treatment options, and long-term outcome. Individual clinicians
      can assist in these efforts by the prompt reporting of cases of AFM to the US
      Centers for Disease Control and Prevention.

PMID- 29181602
TI  - Long Parallel Stent Grafts for the Treatment of Complex Aortic Aneurysms.
AB  - PURPOSE: To describe our experience with the chimney technique in endovascular
      aneurysm repair (ch-EVAR) using long parallel grafts (PGs) of 100 mm or more for
      the treatment of complex aortic aneurysms. MATERIALS AND METHODS: From 2009 to
      2016, data were prospectively collected for patients who underwent ch-EVAR using
      long PGs. Data included patient demographics and aortic anatomy, technical
      success, patency and reintervention rate. RESULTS: A total of 29 long PGs were
      placed in 18 patients (males 16, average age 71 years). Nine (50%) suffered from
      thoracoabdominal aortic aneurysms, 4 (22%) from juxtarenal aortic aneurysms and 3
      (17%) from suprarenal aortic aneurysms and 2 (11%) were treated for abdominal
      aortic aneurysms that required revascularization of a pelvic kidney. Twenty (70%)
      of the PGs were 100 mm in length, and 9 (30%) were 150 mm. Long PGs were
      successfully placed in 16 (89%) patients. Two patients (11%) expired in the
      perioperative period. Mean period of follow-up was 12 months (range 1-43 months).
      Sac size decreased in size or remained unchanged in 13 patients (72%). Three
      patients with sac enlargement underwent successful endovascular treatment the
      type 1A gutter endoleaks. None required reintervention of the PGs. Three patients
      expired, none from aneurysm-related deaths. CONCLUSION: The use of long PGs is a
      feasible technique and provides a durable repair of complex aortic aneurysms in
      midterm follow-up. Despite the length of the PGs, gutter endoleaks are
      encountered only in a minority of the cases and can be treated minimally invasive
      techniques.

PMID- 29181603
TI  - Immediate Resolution of a Grade 3 Varicocele Post-Prostatic Artery Embolisation
      (PAE).

PMID- 29181604
TI  - Reply to Letter.

PMID- 29181605
TI  - Symptomatic Heart Failure After Transjugular Intrahepatic Portosystemic Shunt
      Placement: Incidence, Outcomes, and Predictors.
AB  - PURPOSE: To assess the incidence of symptomatic heart failure (SHF) occurring
      after transjugular intrahepatic portosystemic shunt (TIPS) placement, identify
      potential predictors of SHF, and evaluate clinical presentation and outcomes in
      cases of post-TIPS SHF. MATERIALS AND METHODS: A prospectively maintained TIPS
      database was used to identify patients who underwent new TIPS placements at a
      large urban tertiary care center between 1995 and 2014. SHF was defined as
      otherwise unexplained new-onset dyspnea, hypoxemia, radiologic pulmonary edema,
      an increased need for diuretics, or need for intubation within 7 days after TIPS
      placement. Cases of deaths occurring within 7 days due to septic shock,
      continuing gastrointestinal bleed, or multi-organ failure were excluded. A
      control group consisting of a random sample of 40 patients from the same TIPS
      database was created. Uni-variable analysis was performed to assess differences
      between patients with and without post-TIPS SHF. RESULTS: Of the 934 TIPS
      procedures performed during the study period, 883 met the inclusion criteria.
      Eight (0.9%) patients developed SHF, usually manifested by hypoxemia (50%) or
      dyspnea (25%) within 48 h. Patients with SHF had higher pre-TIPS right atrial (p
      = 0.03) and portal vein (p = 0.01) pressures, higher albumin (p = 0.02), and
      higher prothrombin time (p = 0.02). CONCLUSION: Post-TIPS SHF is rare. Higher pre
      TIPS right atrial and portal vein pressures are likely to predispose patients to
      this complication. Close monitoring may be warranted in these patients. In our
      eight patients, post-TIPS SHF did not result in poor outcomes.

PMID- 29181606
TI  - Trace Element Concentrations in Tree Leaves and Lichen Collected Along a Metal
      Pollution Gradient Near Olkusz (Southern Poland).
AB  - The aim of the study was to assess the metal pollution in the vicinity of the
      Bukowno smelter near Olkusz in southern Poland. Birch and oak leaves, pine
      needles and a lichen Hypogymnia physodes, overgrowing pine bark were collected at
      stands at different distances from the smelter and analysed for cadmium (Cd),
      copper (Cu), lead (Pb) and zinc (Zn) content. Concentrations of metals in the
      lichen were usually higher than in the tree leaves/needles and decreased with
      distance from the smelter, apart from the Cu content. The strongest correlation
      was noticed between Cd and Pb concentrations, which indicates a common pollution
      source (the smelter). Our results show that birch leaves can be potentially
      useful as a bioindicator of Zn air pollution since this species was shown to
      accumulate high amounts of zinc, related to environmental pollution with that
      metal, in their leaves.

PMID- 29181607
TI  - Cryptosporidium spp. Contamination in Perna perna Mussels Destined for Human
      Consumption in Southeastern Rio de Janeiro, Brazil.
AB  - Cryptosporidium spp. has been recognized as an important pathogen. As bivalve
      mollusks are noted as potential sources of several pathogens due to their
      consumption as foodstuffs, the aim of this study was to investigate the
      occurrence of Cryptosporidium spp. oocysts in Perna perna mussels and in seawater
      samples from a mussel farm in Southeastern Brazil, where mussels are grown
      directly in the sea, attached to ropes. Oocysts were observed by microscopy and
      confirmed by an enzyme-linked immunosorbent assay. Oocysts were present in mussel
      gills and GI tracts, as well as in the seawater. Of the 100 females, 10% and 11%
      showed contaminated GI tracts and gills, respectively, while this rate was lower
      in males, at 5% and 8.9%. Oocysts were present in higher amounts in the GI tract
      compared to gills and water. Contamination of the study area is apparent, leading
      to public health risks. More in-depth studies are needed, including molecular
      investigations, to identify Cryptosporidium species in mussels, as well as the
      implementation of monitoring actions in animals destined for human consumption.

PMID- 29181609
TI  - A New Class III Antiarrhythmic Drug Niferidil Prolongs Action Potentials in
      Guinea Pig Atrial Myocardium via Inhibition of Rapid Delayed Rectifier.
AB  - PURPOSE: A new class III antiarrhythmic drug niferidil (RG-2) has been introduced
      as a highly effective therapy for cases of persistent atrial fibrillation, but
      ionic mechanisms of its action are poorly understood. In the present study, the
      effects of niferidil on action potential (AP) waveform and potassium currents
      responsible for AP repolarization were investigated in guinea pig atrial
      myocardium. METHODS: APs were recorded with sharp glass microelectrodes in
      multicellular atrial preparations. Whole-cell patch-clamp technique was used to
      measure K+ currents in isolated myocytes. RESULTS: In multicellular atrial
      preparations, 10-8 M niferidil effectively prolonged APs by 15.2 +/- 2.8% at 90%
      repolarization level. However, even the highest tested concentrations, 10-6 M and
      10-5 M failed to prolong APs more than 32.5% of control duration. The estimated
      concentration of niferedil for half-maximal AP prolongation was 1.13 * 10-8 M.
      Among the potassium currents responsible for AP repolarization phase, I K1 was
      found to be almost insensitive to niferidil. However, another inward rectifier, I
      KACh, was effectively suppressed by micromolar concentrations of niferidil with
      IC50 = 9.2 * 10-6 M. I KATP was much less sensitive to the drug with IC50 = 2.26
      * 10-4 M. The slow component of delayed rectifier, I Ks, also demonstrated low
      sensitivity to niferidil-the highest used concentration, 10-4 M, decreased peak I
      Ks density to 46.2 +/- 5.5% of control. Unlike I Ks, the rapid component of
      delayed rectifier, I Kr, appeared to be extremely sensitive to niferidil. The
      IC50 was 1.26 * 10-9 M. I Kr measured in ventricular myocytes was found to be
      less sensitive to niferidil with IC50 = 3.82 * 10-8 M. CONCLUSIONS: Niferidil
      prolongs APs in guinea pig atrial myocardium via inhibition of I Kr.

PMID- 29181608
TI  - Immunolocalization patterns of cytokeratins during salivary acinar cell
      development in mice.
AB  - Embryonic development of the mouse salivary glands begins with epithelial
      thickening and continues with sequential changes from the pre-bud to terminal bud
      stages. After birth, morphogenesis proceeds, and the glands develop into a highly
      branched epithelial structure that terminates with saliva-producing acinar cells
      at the adult stage. Acinar cells derived from the epithelium are differentiated
      into serous, mucous, and seromucous types. During differentiation, cytokeratins,
      intermediate filaments found in most epithelial cells, play vital roles. Although
      the localization patterns and developmental roles of cytokeratins in different
      epithelial organs, including the mammary glands, circumvallate papilla, and sweat
      glands, have been well studied, their stage-specific localization and
      morphogenetic roles during salivary gland development have yet to be elucidated.
      Therefore, the aim of this study was to determine the stage and acinar cell type
      specific localization pattern of cytokeratins 4, 5, 7, 8, 13, 14, 18, and 19 in
      the major salivary glands (submandibular, sublingual, and parotid glands) of the
      mouse at the E15.5, PN0, PN10, and adult stages. In addition, cell physiology,
      including cell proliferation, was examined during development via immunostaining
      for Ki67 to understand the cellular mechanisms that govern acinar cell
      differentiation during salivary gland morphogenesis. The distinct localization
      patterns of cytokeratins in conjunction with cell physiology will reveal the
      roles of epithelial cells in salivary gland formation during the differentiation
      of serous, mucous or seromucous salivary glands.

PMID- 29181610
TI  - Barriers to Beta-Blocker Use and Up-Titration Among Patients with Heart Failure
      with Reduced Ejection Fraction.
AB  - PURPOSE: For patients with heart failure with reduced ejection fraction (HFrEF),
      guidelines recommend use of beta-blockers with gradual up-titration. However,
      many patients with HFrEF do not use beta-blockers and up-titration is rare. Our
      purpose was to identify and rank barriers to beta-blocker use and up-titration
      from the perspective of primary care physicians. METHODS: We conducted 4
      moderated, structured group discussions among 19 primary care physicians using
      the nominal group technique; 16 participants also completed a survey.
      Participants generated lists of barriers to beta-blocker use and up-titration
      among patients with HFrEF. Each participant had six votes with three votes
      assigned to the item ranked most important, two to the second most important
      item, and one to the third most important item. Investigators characterized items
      into themes. The percentage of available votes was calculated for each theme.
      RESULTS: Fifteen of 16 participating primary care physicians who completed the
      survey reported that management of beta-blockers was their responsibility.
      Treatment/side effects, particularly hypotension, were identified as the most
      important barrier for beta-blocker use (72% of available votes) followed by
      polypharmacy (11%), healthcare system barriers (10%), and comorbidities (6%).
      Barriers to up-titration included treatment/side effects (49% of available
      votes), patient communication/buy-in (21%), polypharmacy (13%), and healthcare
      system barriers (8%). CONCLUSIONS: Many barriers to guideline concordant use of
      beta-blockers among patients with HFrEF identified by primary care providers are
      not readily modifiable. Addressing these barriers may require development,
      testing, and dissemination of protocols for beta-blocker initiation and up
      titration that are safe and appropriate in primary care.

PMID- 29181612
TI  - Hot Topics in Ecohealth Research: A Joint Japanese-Swiss Perspective.

PMID- 29181613
TI  - SimpleITK Image-Analysis Notebooks: a Collaborative Environment for Education and
      Reproducible Research.
AB  - Modern scientific endeavors increasingly require team collaborations to construct
      and interpret complex computational workflows. This work describes an image
      analysis environment that supports the use of computational tools that facilitate
      reproducible research and support scientists with varying levels of software
      development skills. The Jupyter notebook web application is the basis of an
      environment that enables flexible, well-documented, and reproducible workflows
      via literate programming. Image-analysis software development is made accessible
      to scientists with varying levels of programming experience via the use of the
      SimpleITK toolkit, a simplified interface to the Insight Segmentation and
      Registration Toolkit. Additional features of the development environment include
      user friendly data sharing using online data repositories and a testing framework
      that facilitates code maintenance. SimpleITK provides a large number of examples
      illustrating educational and research-oriented image analysis workflows for free
      download from GitHub under an Apache 2.0 license:
      github.com/InsightSoftwareConsortium/SimpleITK-Notebooks .

PMID- 29181614
TI  - Maternal mortality in Sierra Leone: from civil war to Ebola and the Sustainable
      Development Goals.

PMID- 29181611
TI  - Human-Wildlife Interactions Predict Febrile Illness in Park Landscapes of Western
      Uganda.
AB  - Fevers of unknown origin complicate treatment and prevention of infectious
      diseases and are a global health burden. We examined risk factors of self
      reported fever-categorized as "malarial" and "nonmalarial"-in households adjacent
      to national parks across the Ugandan Albertine Rift, a biodiversity and emerging
      infectious disease hotspot. Statistical models fitted to these data suggest that
      perceived nonmalarial fevers of unknown origin were associated with more frequent
      direct contact with wildlife and with increased distance from parks where
      wildlife habitat is limited to small forest fragments. Perceived malarial fevers
      were associated with close proximity to parks but were not associated with direct
      wildlife contact. Self-reported fevers of any kind were not associated with
      livestock ownership. These results suggest a hypothesis that nonmalarial fevers
      in this area are associated with wildlife contact, and further investigation of
      zoonoses from wildlife is warranted. More generally, our findings of land use
      disease relationships aid in hypothesis development for future research in this
      social-ecological system where emerging infectious diseases specifically, and
      rural public health provisioning generally, are important issues.

PMID- 29181615
TI  - Right-Ear Advantage for Speech-in-Noise Recognition in Patients with
      Nonlateralized Tinnitus and Normal Hearing Sensitivity.
AB  - Despite having normal hearing sensitivity, patients with chronic tinnitus may
      experience more difficulty recognizing speech in adverse listening conditions as
      compared to controls. However, the association between the characteristics of
      tinnitus (severity and loudness) and speech recognition remains unclear. In this
      study, the Quick Speech-in-Noise test (QuickSIN) was conducted monaurally on 14
      patients with bilateral tinnitus and 14 age- and hearing-matched adults to
      determine the relation between tinnitus characteristics and speech understanding.
      Further, Tinnitus Handicap Inventory (THI), tinnitus loudness magnitude
      estimation, and loudness matching were obtained to better characterize the
      perceptual and psychological aspects of tinnitus. The patients reported low THI
      scores, with most participants in the slight handicap category. Significant
      between-group differences in speech-in-noise performance were only found at the 5
      dB signal-to-noise ratio (SNR) condition. The tinnitus group performed
      significantly worse in the left ear than in the right ear, even though bilateral
      tinnitus percept and symmetrical thresholds were reported in all patients. This
      between-ear difference is likely influenced by a right-ear advantage for speech
      sounds, as factors related to testing order and fatigue were ruled out.
      Additionally, significant correlations found between SNR loss in the left ear and
      tinnitus loudness matching suggest that perceptual factors related to tinnitus
      had an effect on speech-in-noise performance, pointing to a possible interaction
      between peripheral and cognitive factors in chronic tinnitus. Further studies,
      that take into account both hearing and cognitive abilities of patients, are
      needed to better parse out the effect of tinnitus in the absence of hearing
      impairment.

PMID- 29181616
TI  - Highlight report: prediction of drug induced liver injury (DILI) with human
      hepatocytes in vitro.

PMID- 29181617
TI  - Occult invasion of sternothyroid muscle by differentiated thyroid cancer.
AB  - PURPOSE: To determine the incidence of occult invasion of sternothyroid by
      differentiated thyroid cancer (DTC) and identify clinico-pathological features
      associated with the same. METHODS: Retrospective study of a consecutive series of
      DTC patients undergoing surgery, with preoperative ultrasound showing no evidence
      of strap muscle invasion. All had en bloc excision of sternothyroid muscle along
      with thyroidectomy. Incidence of microscopic invasion of sternothyroid and
      clinicopathologic features associated with the same, were studied. RESULTS: A
      total of 76 patients with DTC (2010-2014) were identified, of whom 62 met the
      inclusion criteria and were included in this study. Of these, 22 (36%) had no
      extrathyroidal extension (ETE), 30 (48%) had minimal ETE without sternothyroid
      invasion and 10 (16%) had minimal ETE with microscopic sternothyroid invasion.
      The mean tumor sizes of the three sub-groups were 1.9, 3.1 and 4.9 cm,
      respectively, with a significant difference between no ETE and sternothyroid
      invaded sub-groups (p = 0.03). Out of the 40 cases with minimal ETE, 3 (7.5%) had
      positive tumor microscopic margin. Retaining sternothyroid in situ would have
      theoretically increased this proportion to 27.5%. Over a median follow-up of 52
      months, 58 (94%) patients remained structurally disease free, with only 1 local
      recurrence. CONCLUSION: Occult invasion of sternothyroid muscle occurred in 16%
      of DTC in this series. Excision of the muscle en bloc with thyroidectomy,
      particularly in larger tumors, may confer benefit in accurately staging the
      disease, encompassing occult ETE and achieving clear microscopic margins.

PMID- 29181618
TI  - Quality of life in hypoparathyroidism.

PMID- 29181619
TI  - MicroRNA-326 contributes to autoimmune thyroiditis by targeting the Ets-1
      protein.
AB  - PURPOSE: MicroRNA-326 (miR-326), as a member of the microRNA (miRNA) family,
      which includes endogenous single-stranded, conserved, noncoding small RNAs, has
      been reported to play important roles in autoimmune diseases such as multiple
      sclerosis and systemic lupus erythematosus. However, few studies of the role of
      miR-326 in autoimmune thyroiditis (AIT) have been published. Here, we explored
      the roles of miR-326 and the involved pathway in iodine-induced AIT. METHODS:
      NOD.H-2h4 mice, which are a model of human AIT, were randomly divided into a
      normal water control group and a high-iodine group. Mice in the high-iodine group
      were administered 0.05% NaI (~1000 times the normal daily iodine intake), and
      mice in the control group received sterile water. Furthermore, we evaluated small
      interfering RNA (siRNA) interference in spleen mononuclear cell experiments in
      vitro. RESULTS: In this study, we found that Th17 cells were significantly
      increased with a high expression of miR-326 in an iodine-induced thyroiditis
      NOD.H-2h4 mouse model. In addition, the expression of Ets-1 protein, a negative
      regulator of Th17 differentiation, was significantly decreased. Intriguingly, our
      analysis showed that Ets-1 protein expression was negatively correlated with miR
      326 levels in AIT mice (r = -0.814, p < 0.01). Our study indicated that miR-326
      inhibited Ets-1 protein expression and promoted the differentiation of Th17 cells
      during the onset and development of AIT. The addition of a miR-326 inhibitor
      reversed Th17 cell production and Ets-1 protein expression, supporting this
      hypothesis. CONCLUSIONS: The results of our study suggest that miR-326 may target
      the Ets-1 protein to contribute to iodide-induced thyroiditis, providing a new
      theoretical basis for the use of miRNA targeting therapy for the treatment of
      autoimmune diseases.

PMID- 29181620
TI  - Consumption of heavy metal contaminated foods and associated risks in Bangladesh.
AB  - This study investigated the magnitude of heavy metal contamination and determined
      the carcinogenic as well as non-carcinogenic risks associated with selected food
      consumption in Bangladesh. Commonly consumed varieties of rice, vegetables, and
      fish samples were analyzed to measure the concentrations of heavy metals such as
      cadmium, chromium, lead, arsenic, manganese, nickel, and zinc. These staple food
      items showed the greatest probabilities of heavy metal contamination in different
      phases of their production and marketing. Wide variations of metal concentrations
      were observed. Specifically, estimated daily intakes of arsenic and cadmium
      exceeded allowable daily intakes in all three food items. Toxicity scores of the
      metals were evaluated, and a comprehensive risk assessment was conducted to
      quantify the risks associated with the daily food consumption. Except for cadmium
      and lead in vegetables, all the contaminants present in each food item posed
      significant levels of carcinogenic risks up to 2.99 * 10-3 compared to the EPA
      recommended carcinogenic risk level of 1.0 * 10-6. Cadmium and arsenic intake due
      to rice consumption also posed unsafe levels of non-carcinogenic risks of 4.587
      and 6.648, respectively, compared to the EPA recommended non-carcinogenic risk
      level of 1.0. Finally, a revised set of permissible limits was proposed for the
      heavy metals detected in the food items. Those permissible limits would ensure
      the risks associated with food consumption below the allowable carcinogenic and
      non-carcinogenic risk levels. Thus, this comprehensive approach would provide
      guidelines to formulate adequate control measures and regulatory limits of toxic
      metals in foods produced and marketed in Bangladesh.

PMID- 29181621
TI  - Monocyte chemoattractant protein-1 as a marker of systemic lupus erythematosus:
      an observational study.
AB  - There is a pivotal need for new markers to be tested in every day clinical
      practice for systemic lupus erythematosus (SLE) and lupus nephritis (LN). The
      levels of monocyte chemoattractant protein-1 (MCP-1) in the serum and urine of 72
      SLE patients (27 with LN and 45 without LN involvement) and 30 healthy
      individuals were studied to establish their clinical significance. The SLE
      Disease Activity Index (SLEDAI) was used to establish the disease activity. Urine
      and serum MCP-1 was determined using the sandwich enzyme immunosorbent assay.
      Urinary, but not serum MCP-1, positively correlated with proteinuria (r = 0.839;
      p < 0.001) and negatively correlated with glomerular filtration, evaluated using
      the modification of diet in renal disease (MDRD) formula (r = - 0.293; p < 0.05),
      and with C3 complement component in active LN patients (r = - 0.519, p = 0.019).
      Both serum and urinary MCP-1 demonstrated a positive correlation with SLEDAI (r =
      0.318; p < 0.01 and r = 0.431; p < 0.001). We also demonstrated that the levels
      of serum and urinary MCP-1 were significantly higher in patients with SLE
      compared to healthy controls, regardless of the disease activity and renal
      involvement. We recommend MCP-1 measurement in the routine laboratory follow-up
      of the SLE patients.

PMID- 29181622
TI  - Neuromuscular fatigue is weakly associated with perception of fatigue and
      function in patients with rheumatoid arthritis.
AB  - To assess electromyographic parameters of neuromuscular fatigue in knee extensors
      and their association with clinical, functional and emotional features in
      patients with rheumatoid arthritis (RA). Thirty-eight female patients with RA
      participated. Electromyography parameters (changes in signal amplitude,
      represented by the root mean square, and frequency content, represented by median
      frequency-MDF) were assessed during a submaximal (60%) isometric contraction of
      the knee extensors, sustained for 60 s. Clinical characteristics; the 28-joint
      Disease Activity Score (DAS-28) in which includes count of swollen joints (out of
      the 28) and tender joints (out of the 28), the erythrocyte sedimentation rate and
      global disease activity measured on a visual analogue scale; serum C reactive
      protein (CRP); information on treatment; the Health Assessment Questionnaire; the
      Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F); the
      Short Form Health Survey (SF-36) and the International Physical Activity
      Questionnaire (IPAQ), were also assessed. The mean patient age was 51.0 +/- 8.2
      years, mean disease activity score was 11.5 +/- 7.1, and mean CRP level was 8.0
      +/- 7.8 mg/dL. There was a moderate correlation between MDF and age (r = 0.5), as
      well as weak correlations of MDF with FACIT-F (r = 0.3), physical functioning (r
      = - 0.3) and vitality domains (r = - 0.3) of the SF-36, and IPAQ (r = - 0.3) (p
      <= 0.05 for all). No association was observed between electromyography
      measurements and clinical or treatment features. The electromyographic parameter
      MDF was correlated with perception of fatigue, age, physical functioning and
      vitality domains of SF-36, and physical activity level in this sample. These
      results indicate that primary muscle factors should also be considered when
      managing perceived fatigue in patients with RA.

PMID- 29181623
TI  - Complete genome sequence of shrimp hemocyte iridescent virus (SHIV) isolated from
      white leg shrimp, Litopenaeus vannamei.
AB  - Infection with shrimp hemocyte iridescent virus (SHIV), a new virus of the family
      Iridoviridae isolated in China, results in a high mortality rate in white leg
      shrimp (Litopenaeus vannamei). The complete genome sequence of SHIV was
      determined and analyzed in this study. The genomic DNA was 165,809 bp long with
      34.6% G+C content and 170 open reading frames (ORFs). Dotplot analysis showed
      that the longest repetitive region was 320 bp in length, including 11 repetitions
      of an 18-bp sequence and 3.1 repetitions of a 39-bp sequence. Two phylogenetic
      trees were constructed based on 27 or 16 concatenated sequences of proteins
      encoded by genes that are conserved between SHIV homologous and other iridescent
      viruses. The results of this study, suggest that SHIV should be considered a
      member of the proposed new genus "Xiairidovirus".

PMID- 29181624
TI  - Significant differences in the intra-host genetic diversity of Helicoverpa
      armigera nucleopolyhedrovirus dnapol after serial in vivo passages in the same
      insect population.
AB  - A denaturing gradient gel electrophoresis assay was used to assess the genetic
      diversity within a region of the DNA polymerase gene (dnapol) in Helicoverpa
      armigera nucleopolyhedrovirus (HearNPV) populations over serial in vivo passages.
      There was no evidence of movement towards a consensus dnapol variant composition
      in the different host larvae after multiple per os passages. The study showed
      that the HearNPV variant structure after in vivo passages in the same host
      population is not necessarily convergent, and that it may be reasonable to expect
      significant differences in intra-host HearNPV genetic diversity after inoculation
      of larvae with a genotypically-diverse HearNPV inoculum.

PMID- 29181625
TI  - Development of a high-resolution infrared thermographic imaging method as a
      diagnostic tool for acute undifferentiated limp in young children.
AB  - Acute limp is a common presenting condition in the paediatric emergency
      department. There are a number of causes of acute limp that include traumatic
      injury, infection and malignancy. These causes in young children are not easily
      distinguished. In this pilot study, an infrared thermographic imaging technique
      to diagnose acute undifferentiated limp in young children was developed.
      Following required ethics approval, 30 children (mean age = 5.2 years, standard
      deviation = 3.3 years) were recruited. The exposed lower limbs of participants
      were imaged using a high-resolution thermal camera. Using predefined regions of
      interest (ROI), any skin surface temperature difference between the healthy and
      affected legs was statistically analysed, with the aim of identifying limp. In
      all examined ROIs, the median skin surface temperature for the affected limb was
      higher than that of the healthy limb. The small sample size recruited for each
      group, however, meant that the statistical tests of significant difference need
      to be interpreted in this context. Thermal imaging showed potential in helping
      with the diagnosis of acute limp in children. Repeating a similar study with a
      larger sample size will be beneficial to establish reproducibility of the
      results. Graphical abstract A young child with an acute undifferentiated limp
      undergoes thermal imaging and the follow on image analysis assists the limp
      diagnosis.

PMID- 29181626
TI  - Pure alexia: two cases and a new neuroanatomical classification.
AB  - Pure alexia without visual or language accompanying deficits (isolated pure
      alexia), represents an infrequent finding in clinical practice. It has been
      linked to lesions involving the splenium of the callosal corpus in classical
      descriptions; however, it has also been reported after occipito-temporal cortex
      damage in the absence of white matter implication. In this regard, a functional
      region called the visual word form area has been recently related to the
      posterior aspect of the occipitotemporal gyrus. We report two new cases of
      cortical hematomas leading to this rare condition and we discuss the
      neuroanatomical evolution of this syndrome. Finally, we propose a new
      classification of pure alexia based on the neuroanatomical location of the
      lesion, namely: (1) disconnection alexia, after posterior and dorsal lesions
      involving the splenium of the callosal corpus or the paraventricular white
      matter, often associated with visual deficits, and (2) cortical alexia, after
      more anterior and ventral lesions in the occipito-temporal cortex with damage of
      the visual word form area, that usually manifests as isolated pure alexia.

PMID- 29181627
TI  - Pompe disease in Austria: clinical, genetic and epidemiological aspects.
AB  - In this study, we performed a survey of infantile and late-onset Pompe disease
      (IOPD and LOPD) in Austria. Paediatric and neuromuscular centres were contacted
      to provide a set of anonymized clinical and genetic data of patients with IOPD
      and LOPD. The number of patients receiving enzyme replacement therapy (ERT) was
      obtained from the pharmaceutical company providing alglucosidase alfa. We found
      25 patients in 24 families, 4 IOPD and 21 LOPD with a resulting prevalence of
      1:350,914. The most frequent clinical manifestation in LOPD was a lower limb
      girdle phenotype combined with axial weakness. Three patients were clinically
      pauci- or asymptomatic and were diagnosed because of persistent hyperCKemia.
      Diagnostic delay in LOPD was 7.4 +/- 9.7 years. The most common mutation was c.
      32-13T > G. All IOPD and 17 symptomatic LOPD patients are receiving ERT.
      Standardized follow-up was only available in six LOPD patients for the 6-min walk
      test (6minWT) and in ten for the forced vital capacity (FVC). Mean FVC did not
      decline (before ERT; 63.6 +/- 39.7%; last evaluation during ERT: 61.9 +/- 26.9%;
      P = 0.5) while there was a trend to decline in the mean distance covered by the
      6minWT (before ERT: 373.5 +/- 117.9 m; last evaluation during ERT: 308.5 +/-
      120.8 m; P = 0.077). The study shows a lower prevalence of Pompe disease in
      Austria than in other European countries and corroborates a limb-girdle phenotype
      with axial weakness as the most common clinical presentation, although
      asymptomatic hyperCKemia may be the first indication of LOPD.

PMID- 29181628
TI  - The major contribution of the DNA damage-triggered reactive oxygen species
      production to cell death: implications for antimicrobial and cancer therapy.
AB  - Genotoxic agents damage DNA, block DNA replication and provoke cell death.
      However, there is growing evidence that an important part of their cytotoxicity
      results from metabolic disturbances induced by treatment. This review article
      describes how increased production of the reactive oxygen species (ROS) induced
      by different genotoxic agents contribute to death of prokaryotic and eukaryotic
      cells. ROS are byproducts of normal cellular functioning. Because ROS are
      damaging cellular macromolecules, they are constantly eliminated by protective
      antioxidant mechanisms. However, even a small increase in ROS production may have
      deleterious consequences because cells possess just enough defensive mechanisms
      to protect themselves against endogenously produced ROS. Therefore, it may be
      possible to enhance cytotoxic potential of antimicrobial and anticancer drugs by
      increasing ROS production or by inhibiting cellular antioxidant systems.

PMID- 29181629
TI  - Linking neuronal structure to function in rodent hippocampus: a methodological
      prospective.
AB  - Since the discovery of place cells, hippocampus-dependent spatial navigation has
      proven to be an ideal model system for resolving the relationship between neural
      coding and behavior. Electrical recordings from the hippocampal formation in
      freely moving animals have revealed a rich repertoire of spatial firing patterns
      and have enormously advanced our understanding of the neural principles of
      spatial representation. However, limited progress has been achieved in resolving
      the underlying cellular mechanisms. This is partially attributable to the
      inability of standard recording techniques to link neuronal structure to function
      directly. In this review, we summarize recent efforts aimed at filling this gap.
      We also highlight the development of methodologies that allow functional
      measurements from identified neuronal elements in behaving rodents. Recent
      progress in the dentate gyrus serves as a showcase to reveal the potential of
      such methodologies and the necessity of resolving structure-function
      relationships in order to access the cellular mechanisms of hippocampal circuit
      computations.

PMID- 29181630
TI  - Detection and complete genome characteristics of Posavirus 1 from pigs in China.
AB  - Porcine stool-associated RNA virus 1 (Posavirus 1) is a novel member of
      picornaviruses and first identified from fecal samples of 30-day-old pigs with
      diarrhea in USA in 2011. To evaluate the existence of Posavirus 1 in swine herds,
      118 clinical samples from diarrheal pigs and 31 fecal swabs from healthy pigs
      were collected and detected by reverse transcription-polymerase chain reaction
      (RT-PCR) using Posavirus 1-specific primers. Only five fecal samples from
      diarrheal pigs on two swine farms were positive for Posavirus 1. The complete
      genome sequences [excluding poly (A) tail] of two representative isolates SDQD-25
      and HBTS-11 are determined and consist of 9840 and 9819 nucleotides in length,
      and encode one putative polyprotein of 3070 and 2952 amino acids, respectively.
      They share 90.3% homology with each other and 81.3-95.4% homologies with American
      Posavirus 1 isolates or strains at the nucleotide sequence level. The
      phylogenetic analysis based on the entire genomes of reference picornavirus
      strains or isolates showed SDQD-25, HBTS-11 cluster together with American
      Posavirus 1 isolates or strains, yet are clearly distant from the other
      picornaviruses. The complete genome sequences of Chinese Posavirus 1 isolates
      will enrich the information of Posavirus 1 sequence database and further expedite
      posavirus research on the genetic diversity, epidemiology, and evolution in
      China.

PMID- 29181631
TI  - A novel Bi4Ti3O12/Ag3PO4 heterojunction photocatalyst with enhanced
      photocatalytic performance.
AB  - In this work, we integrated Ag3PO4 with Bi4Ti3O12 to form Bi4Ti3O12/Ag3PO4
      heterojunction nanocomposites by an ion-exchange method. The as-prepared
      Bi4Ti3O12/Ag3PO4 composites were systematically characterized by means of XRD,
      SEM, TEM, BET, XPS, UV-vis DRS, EIS, PL spectroscopy, and photocurrent response.
      SEM, TEM, and XPS results demonstrate the creation of Bi4Ti3O12/Ag3PO4
      heterojunction with obvious interfacial interaction between Bi4Ti3O12 and Ag3PO4.
      PL spectra, EIS spectra, and photocurrent responses reveal that the composites
      display an enhanced separation efficiency of photogenerated electron-hole pairs,
      which is due to the charge transfer between Bi4Ti3O12 and Ag3PO4. Rhodamine B
      (RhB) was chosen as the target organic pollutant to evaluate its degradation
      behavior over Bi4Ti3O12/Ag3PO4 composites under simulated sunlight irradiation.
      Compared to bare Bi4Ti3O12 and Ag3PO4 nanoparticles, the composites exhibit a
      significantly enhanced photocatalytic activity. The highest photocatalytic
      activity is observed for the 10% Bi4Ti3O12/Ag3PO4 composite with 10% Bi4Ti3O12
      content, which is about 2.6 times higher than that of bare Ag3PO4. The
      photocatalytic mechanism involved was investigated and discussed in detail.

PMID- 29181632
TI  - Microbial lipolytic fusion enzymes: current state and future perspectives.
AB  - Genetic fusion of coding ORFs or connection of proteins in a post translational
      process are rather novel techniques to build products called fusion proteins that
      possess combined characteristics of their parental biomolecules. This attractive
      strategy used to create new enzymes not only diversifies their functionality by
      improving thermostability, thermo- and catalytic activity, substrate specificity,
      regio- or enantio-selectivity but also facilitates their purification and
      increases their yield. Many examples of microbial synthetic fusion biocatalysts
      are associated with fused enzymes that are involved in biomass degradation.
      However, one of the leading production segments is occupied by microbial
      lipolytic enzymes (lipases and esterases). As powerful biocatalysts these enzymes
      found their application in detergent, food, oil and fat, pulp and paper, leather,
      textile, cosmetics, biodiesel production industries. Moreover, lipolytic enzymes
      market is predicted to maintain leadership up to the year of 2024 and exceed
      millions of dollars. Recently, creation of lipolytic fusion biocatalysts for
      industrial applications gained more attention since it is not only a way of
      achievement of enzymes with improved properties but also a way to reduce
      industrial energy costs and ensure other economic benefits. This paper provides a
      comprehensive review on current state of microbial lipolytic fusion enzymes and
      their future potential.

PMID- 29181633
TI  - Amphiregulin regulates proliferation and migration of HER2-positive breast cancer
      cells.
AB  - PURPOSE: Tumor initiation and progression rely on cellular proliferation and
      migration. Many factors are involved in these processes, including growth
      factors. Amphiregulin (AREG) is involved in normal mammary development and the
      development of estrogen receptor (ER)-positive breast cancer. The aim of this
      project was to determine if AREG is involved in the proliferation and progression
      of HER2-positive breast cancer. METHODS: Mouse cell lines MMTV-neu, HC-11 and
      COMMA-D, as well as human cell lines MCF10A, SKBR3, HCC1954 and BT474 were used.
      Real-time PCR was used to quantify AREG expression and neutralizing antibodies
      were used to reduce the autocrine/paracrine effects of AREG. Transfections using
      siRNA and shRNA were used to knockdown AREG expression in the cancer cell lines.
      Free-floating sphere formation, colony forming, scratch wound and Transwell
      assays were used to assess the proliferation, tumor forming and migratory
      capacities of transfected cancer cells. RESULTS: We found AREG expression in both
      normal epithelial cell lines and tumor-derived cell lines. Knockdown of AREG
      protein expression resulted in reduced sphere sizes and reduced sphere numbers in
      both mouse and human cancer cells that overexpress erbB2/HER2. AREG was found to
      be involved in cancer cell migration and invasion. In addition, we found that
      AREG expression knockdown resulted in different migration capacities in normal
      and erbB2/HER2 overexpressing cancer cells. CONCLUSIONS: Based on our results we
      conclude that AREG is involved in regulating the proliferation and migration of
      erbB2/HER2-positive breast cancer cells.

PMID- 29181634
TI  - Population structure and virulence gene profiles of Streptococcus agalactiae
      collected from different hosts worldwide.
AB  - Streptococcus agalactiae is a leading cause of morbidity and mortality among
      neonates and causes severe infections in pregnant women and nonpregnant
      predisposed adults, in addition to various animal species worldwide. Still,
      information on the population structure of S. agalactiae and the geographical
      distribution of different clones is limited. Further data are urgently needed to
      identify particularly successful clones and obtain insights into possible routes
      of transmission within one host species and across species borders. We aimed to
      determine the population structure and virulence gene profiles of S. agalactiae
      strains from a diverse set of sources and geographical origins. To this end, 373
      S. agalactiae isolates obtained from humans and animals from five different
      continents were typed by DNA microarray profiling. A total of 242 different S.
      agalactiae strains were identified and further analyzed. Particularly successful
      clonal lineages, hybridization patterns, and strains were identified that were
      spread across different continents and/or were present in more than one host
      species. In particular, several strains were detected in both humans and cattle,
      and several canine strains were also detected in samples from human, bovine, and
      porcine hosts. The findings of our study suggest that although S. agalactiae is
      well adapted to various hosts including humans, cattle, dogs, rodents, and fish,
      interspecies transmission is possible and occurs between humans and cows, dogs,
      and rabbits. The virulence and resistance gene profiles presented enable new
      insights into interspecies transmission and make a crucial contribution to the
      identification of suitable targets for therapeutic agents and vaccines.

PMID- 29181635
TI  - Caryophyllales are the main hosts of a unique set of ectomycorrhizal fungi in a
      Neotropical dry forest.
AB  - The ectomycorrhizal symbiosis was long thought to be restricted to temperate
      forests. However, as tropical forests have been explored, it has become clear
      that these habitats host unique ectomycorrhizal (ECM) fungi. We have been
      exploring tropical dry forests (TDF), which are endangered terrestrial ecosystems
      and hotspots of endemism. Since Fabaceae is the main plant family in this
      environment, we hypothesized that trees in this lineage would be the main ECM
      hosts. We sequenced the ITS rDNA region from fungi and both rbcL and trnL cpDNA
      from plants to identify both symbiotic partners from root tips. The systematic
      position of each symbiont was confirmed by Bayesian phylogenetic inference. We
      identified 20 plant species belonging to 10 families that hosted 19 unique ECM
      fungal species from 5 lineages. Most ECM fungi were associated with
      Caryophyllales, not with Fabaceae. Achatocarpus and Guapira, the main hosts, are
      scattered throughout the forest and are not in monodominant patches. The low ECM
      fungal diversity can be explained by the low density of host plants and their
      high specificity. Our results indicate that Caryophyllales is an important order
      of tropical ECM hosts with at least four independent evolutionary lineages that
      have evolved the ability to form ectomycorrhizae.

PMID- 29181636
TI  - Accounting for local adaptation in ectomycorrhizas: a call to track geographical
      origin of plants, fungi, and soils in experiments.
AB  - Local adaptation, the differential success of genotypes in their native versus
      foreign environments, can influence ecological and evolutionary processes, yet
      its importance is difficult to estimate because it has not been widely studied,
      particularly in the context of interspecific interactions. Interactions between
      ectomycorrhizal (EM) fungi and their host plants could serve as model system for
      investigations of local adaptation because they are widespread and affect plant
      responses to both biotic and abiotic selection pressures. Furthermore, because EM
      fungi cycle nutrients and mediate energy flow into food webs, their local
      adaptation may be critical in sustaining ecological function. Despite their
      ecological importance and an extensive literature on their relationships with
      plants, the vast majority of experiments on EM symbioses fail to report critical
      information needed to assess local adaptation: the geographic origin of the
      plant, fungal inocula, and soil substrate used in the experiment. These omissions
      limit the utility of such studies and restrict our understanding of EM ecology
      and evolution. Here, we illustrate the potential importance of local adaptation
      in EM relationships and call for consistent reporting of the geographic origin of
      plant, soil, and fungi as an important step towards a better understanding of the
      ecology and evolution of EM symbioses.

PMID- 29181637
TI  - Further investigation of relationships between membrane fluidity and ethanol
      tolerance in Saccharomyces cerevisiae.
AB  - Membrane lipid unsaturation index and membrane fluidity have been related to
      yeast ethanol stress tolerance in published studies, however findings have been
      inconsistent. In this study, viability reduction on exposure to 18% (v/v) ethanol
      was compared to membrane fluidity determined by laurdan generalized polarization.
      Furthermore, in the determination of viability reduction, we examined the
      effectiveness of two methods, namely total plate count and methylene violet
      staining. We found a strong negative correlation between ethanol tolerance and
      membrane fluidity, indicated by negative Pearson correlation coefficients of -
      0.79, - 0.65 and - 0.69 for Saccharomyces cerevisiae strains A12, PDM and K7,
      respectively. We found that lower membrane fluidity leads to higher ethanol
      tolerance, as indicated by decreased viability reduction and higher laurdan
      generalized polarization in respiratory phase compared to respiro-fermentative
      phase cells. Total plate count better differentiated ethanol tolerance of yeast
      cells in different growth phases, while methylene violet staining was better to
      differentiate ethanol tolerance of the different yeast strains at a particular
      culture phase. Hence, both viability assessment methods have their own advantages
      and limitations, which should be considered when comparing stress tolerance in
      different situations.

PMID- 29181638
TI  - Synergetic Effect of Graphene and MWCNTs on Microstructure and Mechanical
      Properties of Cu/Ti3SiC2/C Nanocomposites.
AB  - Multi-walled carbon nanotubes (MWCNTs) and graphenes have been taken for novel
      reinforcements due to their unique structure and performance. However, MWCNTs or
      graphenes reinforced copper matrix composites could not catch up with ideal value
      due to reinforcement dispersion in metal matrix, wettability to metal matrix, and
      composite material interface. Taking advantage of the superior properties of one
      dimensional MWCNTs and two-dimensional graphenes, complementary performance and
      structure are constructed to create a high contact area between MWCNTs and
      graphenes to the Cu matrix. Mechanical alloying, hot pressing, and hot isostatic
      pressing techniques are used to fabricate Cu matrix self-lubricating
      nanocomposites. Effects of MWCNTs and graphenes on mechanical properties and
      microstructures of Cu/Ti3SiC2/C nanocomposites are studied. The fracture and
      strengthening mechanisms of Cu/Ti3SiC2/C nanocomposites are explored on the basis
      of structure and composition of Cu/Ti3SiC2/C nanocomposites with formation and
      function of interface.

PMID- 29181639
TI  - Mucositis, peri-implantitis, and survival and success rates of oxide-coated
      implants in patients treated for periodontitis 3- to 6-year results of a case
      series study.
AB  - AIM: The aim of this case-series study is to evaluate the prevalence of
      mucositis, peri-implantitis, and survival and success rates of oxide-coated
      implants in subjects treated for periodontitis. MATERIALS AND METHODS: Twenty
      four subjects treated for generalized chronic periodontitis (GCP) and five
      treated for generalized aggressive periodontitis (GAP) were orally rehabilitated
      with a total of 130 dental implants. Subjects were examined 2 to 4 weeks prior to
      extraction of non-retainable teeth and at insertion of superstructure. Additional
      examinations were performed during a 3-month recall schedule over a 3- to 6-year
      follow-up period. Radiographs were taken after insertion of the superstructure
      and 1, 3, and 5 years later. RESULTS: The results showed implant survival rates
      of 97.1% in GCP subjects versus 96.2% in GAP subjects. The implant success rate
      was 77.9% in GCP subjects and 38.5% in GAP subjects. In GCP subjects, mucositis
      was present in 7.7% and peri-implantitis in 12.5% of the implants. In GAP
      subjects, 28.0% of the implants showed mucositis and 32.0% peri-implantitis.
      Implant failure, mucositis, and peri-implantitis were more evident in GAP
      subjects. Peri-implantitis was more prevalent for implants in the maxilla and
      implants >10 mm. After 5 years, the mean peri-implant bone loss in GAP subjects
      was 2.89 mm and in GCP subjects 1.38 mm. CONCLUSIONS: Periodontally diseased
      subjects treated in a supportive periodontal therapy can be successfully
      rehabilitated with oxide-coated dental implants for a follow-up period of 3- to 6
      years. Implants in the maxilla and GAP subjects were more susceptible to
      mucositis and peri-implantitis, with lower implant survival and success rates.

PMID- 29181640
TI  - Impact of gut microbiota on drug metabolism: an update for safe and effective use
      of drugs.
AB  - The intestinal mucosa and liver have long been considered as the main sites of
      drug metabolism, and the contribution of gut microbiota to drug metabolism has
      been under-estimated. However, it is now generally accepted that the gut
      microbiota plays an important role in drug metabolism prior to drug absorption or
      during enterohepatic circulation via various microbial enzymatic reactions in the
      intestine. Moreover, some drugs are metabolized by gut microbiota to specific
      metabolite(s) that cannot be formed in the liver. More importantly, the
      metabolism of drugs by gut microbiota prior to absorption can alter the systemic
      bioavailability of certain drugs. Therefore, understanding drug metabolism by gut
      microbiota is critical for explaining changes in the pharmacokinetics of drugs,
      which may cause significant alterations in drug-induced pharmacodynamics and
      toxicities. In this review, we describe recent progress with regard to the role
      of metabolism by gut microbiota in some drug-induced alterations of either
      pharmacological or toxicological effects to emphasize the clinical importance of
      gut microbiota for safe and effective use of drugs.

PMID- 29181641
TI  - Effect of photobiomodulation on connective tissue remodeling and regeneration of
      skeletal muscle in elderly rats.
AB  - The purpose of this study was to evaluate the effects of low-level laser therapy
      (LLLT) on morphological aspects, IL-6 and IL-1beta expressions, as well as the
      distribution and organization of collagen in the tibialis anterior (TA) muscle of
      elderly rats submitted to cryoinjury. Histological photomicrographs were taken of
      TA muscles stained with HE and picrosirius red. Immunohistochemistry was used for
      the evaluation of IL-6 and IL-1beta. Male Wistar rats, aged 20 months, were
      distributed into three groups: (1) control animals not injured or treated with
      LLLT (n = 5), (2) cryoinjury without LLLT treatment (n = 15), and (3) cryoinjury
      treated with infrared LLLT (n = 15). LLLT was applied to the TA 2 h after of the
      injury induction and consisted of daily applications until the sacrifice (1, 3,
      and 7 days). The following parameters were used: lambda = 780 nm, power density 1
      W/cm2, output power 40 mW, 10 s per point, 8 points, and 3.2 J of total energy.
      In the histomorphological analysis, the treated group exhibited a significant
      decrease in inflammatory infiltrate (p < 0.001) as well as an increase immature
      fibers and new blood vessels at 7 days compared to the untreated group (p <
      0.05). Furthermore, treatment induced a better collagen distribution and
      organization at 7 days in comparison to the untreated group (p < 0.05). In
      conclusion, LLLT demonstrated a modulatory effect on the muscle repair process in
      elderly animals with regard to the collagen remodeling and morphological aspects
      of muscle tissue.

PMID- 29181642
TI  - Laser photobiomodulation in pressure ulcer healing of human diabetic patients:
      gene expression analysis of inflammatory biochemical markers.
AB  - Pressure ulcers (PU) are wounds located mainly on bone surfaces where the tissue
      under pressure suffers ischemia leading to cellular lesion and necrosis , its
      causes and the healing process depend on several factors. The aim of this study
      was evaluating the gene expression of inflammatory/reparative factors: IL6, TNF,
      VEGF, and TGF, which take part in the tissue healing process under effects of low
      level laser therapy (LLLT). In order to perform lesion area analysis, PUs were
      photographed and computer analyzed. Biochemical analysis was performed sa.mpling
      ulcer border tissue obtained through biopsy before and after laser therapy and
      quantitative real-time PCR (qRT-PCR) analysis. The study comprised eight
      individuals, mean age sixty-two years old, and sacroiliac and calcaneous PU,
      classified as degree III and IV according to the National Pressure Ulcer Advisory
      Panel (NPUAP). PUs were irradiated with low-level laser (InGaAIP, 100 mW, 660
      nm), energy density 2 J/cm2, once a day, with intervals of 24 h, totaling 12
      applications. The lesion area analysis revealed averaged improvement of the
      granulation tissue size up to 50% from pre- to post-treatment. qRT-PCR analysis
      revealed that IL6 values were not significantly different before and after
      treatment, TNF gene expression was reduced, and VEFG and TGF-beta gene expression
      increased after treatment. After LLLT, wounds presented improvement in gross
      appearance, with increase in factors VEFG and TGF-beta, and reduction of TNF;
      despite our promising results, they have to be analyzed carefully as this study
      did not have a control group.

PMID- 29181643
TI  - Vibrational spectroscopy of muscular tissue intoxicated by snake venom and
      exposed to photobiomodulation therapy.
AB  - The pathogenesis of myonecrosis caused by myotoxins from bothropic venom is
      associated with local extracellular matrix (ECM) disintegration, hemorrhage, and
      inflammation. Search for alternative methods associated with serum therapy is
      mandatory to neutralize the fast development of local damage following
      snakebites. The experimental use of photobiomodulation therapy (PBMT) in murine
      models has shown promising results relative to structural and functional recovery
      from bothropic snakebite-induced myonecrosis. This study pioneered in using Raman
      and Fourier transform infrared (FTIR) spectroscopies to characterize biochemical
      alterations in the gastrocnemius that had been injected with Bothrops jararacussu
      venom and exposed to local PBMT. Results show that vibrational spectra from
      lyophilized and diluted venom (1307 cm -1) was also found in the envenomed
      gastrocnemius indicating venom presence in the unirradiated muscle 48 h post
      injection; but any longer visible after PBMT at this time exposure or 72 h post
      injection regardless irradiated or not. Raman and FTIR analyses indicated that
      the bands with higher area and intensity were 1657 and 1547 cm-1 and 1667 and
      1452 cm-1, respectively; all are assignments for proteins, especially collagen,
      and are higher in the PBMT-exposed gastrocnemius. The infrared spectra suggest
      that laser treatment was able to change protein in tissue and that such change
      indicates collagen as the main target. We hypothesize that the findings reflect
      remodeling of ECM with key participation of collagen and faster tissue recovery
      for an anabolic condition.

PMID- 29181645
TI  - Erosion after laparoscopic ventral mesh rectopexy with a biological mesh.

PMID- 29181644
TI  - Effectiveness of a Cocaine Hydrolase for Cocaine Toxicity Treatment in Male and
      Female Rats.
AB  - Development of a truly effective medication for treatment of cocaine abuse has
      been a grand challenge. There is no FDA-approved therapeutic agent specific for
      cocaine addiction or overdose. An enzyme therapy using an efficient cocaine
      metabolizing enzyme could be a promising treatment strategy for cocaine overdose
      and addiction. One of our previously designed cocaine hydrolases (CocHs), known
      as CocH1, was fused with human serum albumin (HSA) to prolong the biological half
      life. The fusion protein CocH1-HSA is an investigational new drug (IND) approved
      by the FDA for clinical trials in cocaine addiction treatment, but not in cocaine
      overdose/toxicity treatment. In the present study, we aimed to evaluate the
      pharmacokinetic profile of CocH1-HSA and its effectiveness for cocaine toxicity
      treatment in male and female rats and demonstrate the clinical potential. The
      data demonstrate that enzyme CocH1-HSA has very similar pharmacokinetic profile
      in male and female rats. For both male and female rats, the enzyme can rapidly
      eliminate cocaine even if the cocaine dose is as high as 180 mg/kg (LD100). Based
      on the animal data, whenever the enzyme is given to a living subject, the
      remaining cocaine in the body will be converted rapidly to physiologically
      inactive metabolites and, thus, reverse the cocaine toxicity and help the subject
      to recover. So, an enzyme therapy using CocH1-HSA can effectively treat cocaine
      toxicity and prevent the subject from further damage by cocaine. The data
      obtained clearly demonstrate the promising clinical potential of CocH1-HSA in
      cocaine overdose treatment for both genders.

PMID- 29181646
TI  - Robiginitalea sediminis sp. nov., isolated from a sea cucumber culture pond.
AB  - A Gram-stain negative, aerobic, non-motile, orange and rod/coccoid-shaped
      bacterium, designated O458T, was isolated from sediment collected from a sea
      cucumber culture pond located in Rongcheng, Shandong province, China (122 degrees
      14'E, 36 degrees 54'N). Comparative analysis of 16S rRNA gene sequences revealed
      that strain O458T is a member of the genus Robiginitalea and is closely related
      to Robiginitalea biformata (95.7% sequence similarity) and Robiginitalea
      myxolifaciens (94.9%). Its DNA G+C content was 55.2 mol%. The strain grew at
      temperatures between 15 and 45  degrees C (optimum 33  degrees C), from pH 6.5 to
      8.5 (optimum pH 7.0-7.5) and between 1.0 and 6.0% (w/v) NaCl (optimum 2.0%).
      Strain O458T was found to contain menaquinon-6 (MK-6) as the only respiratory
      quinone, iso-C15:0, iso-C17:0 3-OH and Summed feature 1 (iso-C15:1 H and/or iso
      C13:0 3-OH) as the major fatty acids. The major polar lipids were
      phosphatidylethanolamine (PE) and four unidentified lipids (L1, L2, L3 and L4).
      On the basis of the results of the phylogenetic and phenotypic analyses it is
      suggested that strain O458T represents a novel species of the genus
      Robiginitalea, for which the name Robiginitalea sediminis sp. nov. is proposed.
      The type strain is O458T (=KCTC 52898T=MCCC 1H00190T).

PMID- 29181648
TI  - Molecular characterization of cytosolic cysteine synthase in Mimosa pudica.
AB  - In the cysteine and mimosine biosynthesis process, O-acetyl-L-serine (OAS) is the
      common substrate. In the presence of O-acetylserine (thiol) lyase (OASTL,
      cysteine synthase) the reaction of OAS with sulfide produces cysteine, while with
      3-hydroxy-4-pyridone (3H4P) produces mimosine. The enzyme OASTL can either
      catalyze Cys synthesis or both Cys and mimosine. A cDNA for cytosolic OASTL was
      cloned from M. pudica for the first time containing 1,410 bp nucleotides. The
      purified protein product from overexpressed bacterial cells produced Cys only,
      but not mimosine, indicating it is Cys specific. Kinetic studies revealed that pH
      and temperature optima for Cys production were 6.5 and 50  degrees C,
      respectively. The measured Km, Kcat, and Kcat Km-1 values were 159 +/- 21 uM,
      33.56 s-1, and 211.07 mM-1s-1 for OAS and 252 +/- 25 uM, 32.99 s-1, and 130.91 mM
      1s-1 for Na2S according to the in vitro Cys assay. The Cy-OASTL of Mimosa pudica
      is specific to Cys production, although it contains sensory roles in sulfur
      assimilation and the reduction network in the intracellular environment of M.
      pudica.

PMID- 29181647
TI  - The role of plant hormones during grafting.
AB  - For millennia, people have cut and joined different plant tissues together
      through a process known as grafting. By creating a chimeric organism, desirable
      properties from two plants combine to enhance disease resistance, abiotic stress
      tolerance, vigour or facilitate the asexual propagation of plants. In addition,
      grafting has been extremely informative in science for studying and identifying
      the long-distance movement of molecules. Despite its increasing use in
      horticulture and science, how plants undertake the process of grafting remains
      elusive. Here, we discuss specifically the role of eight major plant hormones
      during the wound healing and vascular formation process, two phenomena involved
      in grafting. We furthermore present the roles of these hormones during graft
      formation and highlight knowledge gaps and future areas of interest for the field
      of grafting biology.

PMID- 29181650
TI  - Reconstitutive approach for investigating plant vascular development.
AB  - Plants generate various tissues and organs via a strictly regulated developmental
      program. The plant vasculature is a complex tissue system consisting of xylem and
      phloem tissues with a layer of cambial cells in between. Multiple regulatory
      steps are involved in vascular development. Although molecular and genetic
      studies have uncovered a variety of key factors controlling vascular development,
      studies of the actual functions of these factors have been limited due to the
      inaccessibility of the plant vasculature. Thus, to obtain a different
      perspective, culture systems have been widely used to analyze the sequential
      processes that occur during vascular development. A tissue culture system known
      as VISUAL, in which molecular genetic analysis can easily be performed, was
      recently established in Arabidopsis thaliana. This reconstitutive approach to
      vascular development enables this process to be investigated quickly and easily.
      In this review, I summarize our recent knowledge of the regulatory mechanisms
      underlying vascular development and provide future perspectives on vascular
      analyses that can be performed using VISUAL.

PMID- 29181649
TI  - Cell-cell communications and molecular mechanisms in plant sexual reproduction.
AB  - Sexual reproduction is achieved by precise interactions between male and female
      reproductive organs. In plant fertilization, sperm cells are carried to ovules by
      pollen tubes. Signals from the pistil are involved in elongation and control of
      the direction of the pollen tube. Genetic, reverse genetic, and cell biological
      analyses using model plants have identified various factors related to the
      regulation of pollen tube growth and guidance. In this review, I summarize the
      mechanisms and molecules controlling pollen tube growth to the ovule, micropylar
      guidance, reception of the guidance signal in the pollen tube, rupture of the
      pollen tube to release sperm cells, and cessation of the tube guidance signal. I
      also briefly introduce various techniques used to analyze pollen tube guidance in
      vitro.

PMID- 29181652
TI  - Repeat cytoreduction and hyperthermic intraperitoneal chemotherapy for recurrent
      peritoneal carcinomatosis of appendiceal origin.
AB  - BACKGROUND: The purpose of this study was to clarify the role of repeat
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC)
      in the management of recurrent peritoneal carcinomatosis of appendiceal origin.
      METHODS: Data were retrieved on 42 patients who underwent CRS + HIPEC; 29 repeat
      surgical procedures were performed in 13 patients. RESULTS: Complete
      cytoreduction was achieved in 12 of 13 patients by the second CRS. Repeat
      recurrence was detected in 11 patients, eight of whom underwent a third CRS. The
      peritoneal cancer index decreased from initial CRS to repeat CRS but was still
      higher than 18 in nine patients at the second CRS. Preoperative chemotherapy was
      given to three patients with early recurrence. Grade 3-5 morbidity and 90-day
      mortality were not significantly different between initial and repeat CRS. Five
      year survival rates after first and second CRS were 75.5 and 67.7%, respectively.
      Complete cytoreduction at second CRS was a significant prognostic factor. Among
      patients with recurrence after the second CRS, patients who underwent a third CRS
      showed a better prognosis than those who did not. CONCLUSIONS: Repeat CRS is
      oncologically beneficial, and the morbidity rate was as high as that of initial
      CRS. Complete cytoreduction was the key to successful long-term results. Although
      further recurrence was common, aggressive resection was useful, even in cases of
      diffuse recurrence.

PMID- 29181651
TI  - Risk of fatigue in cancer patients receiving anti-EGFR monoclonal antibodies:
      results from a systematic review and meta-analysis of randomized controlled
      trial.
AB  - BACKGROUND: To evaluate the association between fatigue and anti-epidermal growth
      factor receptor monoclonal antibodies (anti-EGFR MAbs), we conducted the first
      meta-analysis to access the incidence and risk of fatigue associated with anti
      EGFR MAbs. METHODS: Electronic databases were searched for randomized controlled
      trials (RCTs) published up to February 2017. Eligible studies were selected
      according to PRISMA statement. Incidence rates, risk ratio (RRs), and 95%
      confidence intervals (CIs) were calculated using fixed-effects or random-effects
      models. Outcomes of quality were summarized in accordance with the GRADE (Grading
      of Recommendations Assessment, Development, and Evaluation) methodology. RESULTS:
      Thirty-five RCTs (including 15,622 patients) were included; median follow-up
      ranged from 8.1 to 71.4 months, and the fatigue events were recorded and graded
      according to the Common Toxicity Criteria for Adverse Events version 2.0 or 3.0
      in most of the included trials. For patients receiving anti-EGFR MAbs, the
      overall incidence of all-grade and high-grade fatigue was 54.1% and 10.5%,
      respectively. Compared with control, anti-EGFR MAbs significantly increased the
      risk of all-grade fatigue (RR 1.10, 95% CI, 1.05-1.14, moderate-quality evidence)
      and high-grade fatigue (RR 1.31, 95% CI, 1.19-1.45, moderate-quality evidence).
      No significant differences among subgroup analyses (anti-EGFR MAbs, tumor type,
      and median follow-up) on high-grade fatigue were observed. No evidence of
      publication bias was observed. CONCLUSION: The present study suggested that anti
      EGFR MAbs may increase the risk of fatigue in cancer patients.

PMID- 29181653
TI  - Acute disseminated encephalomyelitis associated with debut of a late onset
      coeliac disease-a case report.

PMID- 29181654
TI  - Diverse clinical presentations of neurosyphilis: focus on differential diagnosis.

PMID- 29181656
TI  - Questions.

PMID- 29181655
TI  - The organisation of the acute ischemic stroke management: key notes of the
      Italian Neurological Society and of the Italian Stroke Organization.
AB  - The main aim of acute ischemic stroke treatment is the as much possible prompt,
      safe and effective arterial recanalisation, in order to restore reperfusion into
      the ischemic brain area. The procedures obtaining this result are rapidly
      evolving and in the last years, we observed new evidences that affirmed the
      therapeutical benefit of the concomitant treatment using endovenous thrombolysis
      and mechanical thrombectomy in selected patients with ischemic stroke. However,
      all treatments are time-sensitive and the main limitation for their application
      is represented by the time. For this reason, the optimisation of the acute stroke
      management that includes a pre-hospital and an in-hospital phase is essential to
      reduce the avoidable delay, increasing the number of patients potentially
      treatable. The purpose of this document is to define the main elements and to
      suggest the principal key points constituting the optimal pathway of stroke
      management in Italian care settings, in line with the recommendations coming from
      the current national and international guidelines.

PMID- 29181657
TI  - Fitness for Duty Assessments: Teaching Forensic Psychiatry Fellows Best Practices
      in Workplace Safety Consultation.

PMID- 29181658
TI  - Effect of ferric citrate hydrate on FGF23 and PTH levels in patients with non
      dialysis-dependent chronic kidney disease with normophosphatemia and iron
      deficiency.
AB  - BACKGROUND: In patients with normophosphatemia with chronic kidney disease (CKD),
      fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) increase
      urinary phosphate excretion while maintaining serum phosphate within the normal
      range. Recent reports have shown that, in this stage, phosphate binders do not
      decrease serum FGF23 and PTH levels. Iron deficiency promotes transcription of
      FGF23 and iron-supplementation for iron deficiency decreases serum FGF23 levels.
      We hypothesized that ferric citrate hydrate, an iron-based phosphate binder, will
      decrease serum FGF23 levels in patients with non-dialysis-dependent CKD with
      normophosphatemia and iron deficiency. METHODS: This was a single-center,
      randomized, open-label interventional study. The inclusion criteria were as
      follows: (1) eGFR < 45 mL/min/1.73 m2, (2) normophosphatemia, (3) iron
      deficiency. Patients were assigned to the following groups: ferric citrate
      hydrate (FCH)-group, sodium ferrous citrate (SFC)-group, and control-group. After
      12 weeks of intervention, we evaluated serum FGF23 levels and CKD-mineral bone
      disorder markers. RESULTS: There were 17 patients in the FCH-group, 14 in the SFC
      group, and 9 in the control-group. The serum ferritin levels increased in the FCH
      group and SFC-group compared with baseline. Serum FGF23 levels were unchanged;
      the change in the FCH-group was from 52.91 RU/mL (42.48-72.91) to 40.00 RU/mL
      (30.30-58.13) (P = 0.1764). However, in the FCH-group, serum PTH levels
      significantly decreased compared with baseline, from 68.00 pg/mL (49.00-141.00)
      to 60.00 pg/mL (44.00-144.00) (P = 0.0101). CONCLUSION: Iron-based phosphate
      binder did not decrease serum FGF23 levels, but decreased serum PTH levels.

PMID- 29181659
TI  - Decrease in toe pinch force in male type 2 diabetic patients with diabetic
      nephropathy.
AB  - BACKGROUND: The purpose of this cross-sectional study was to investigate the toe
      pinch force (TPF) of type 2 diabetic patients with diabetic nephropathy by
      disease stage, and to clarify the factors affecting the TPF. METHODS: Seventy
      four men with diabetic nephropathy (age: 62.7 +/- 8.9 years, duration of
      diabetes: 14.2 +/- 8.6 years) were enrolled. According to the staging of diabetic
      nephropathy, TPF and knee extension force (KEF) were compared among three groups:
      normoalbuminuria, microalbuminuria, and overt nephropathy. In addition, we
      investigated factors influencing TPF and KEF by performing multiple regression
      analysis. RESULTS: Normoalbuminuria group, microalbuminuria group, and overt
      nephropathy group included 26, 25, and 23 patients, respectively. The TPF of the
      overt nephropathy group (3.15 +/- 0.75 kg) was significantly lower than that of
      the normoalbuminuria (4.2 +/- 0.7 kg, p < 0.001) and microalbuminuria groups
      (3.65 +/- 0.81 kg, p = 0.022). The KEF of the overt nephropathy group (37.1 +/-
      8.3 kgf) was significantly lower than that of the normoalbuminuria group (44.8 +/
      8.3 kgf, p = 0.010). Multiple regression analysis revealed that diabetic
      polyneuropathy (DPN) and diabetic nephropathy were determinant factors of the
      TPF; and age, body mass index, and diabetic nephropathy were determinant factors
      of the KEF. CONCLUSION: We found in male patients with diabetic nephropathy, the
      TPF and KEF decreased with progression of diabetic nephropathy. Furthermore, our
      findings suggest diabetic nephropathy and DPN are critically involved in the
      reduction of TPF and KEF.

PMID- 29181660
TI  - Pre-operative and post-operative estimated glomerular filtration rate in Japanese
      patients with urological malignancies.
AB  - BACKGROUND: The suitable methods evaluating glomerular filtration rate (GFR) have
      not been established in patients undergoing radical nephrectomy (RN) or radical
      nephroureterectomy (RNU) due to urological malignancies in Japan as well as
      worldwide. METHODS: We examined the relationship between creatinine clearance
      based measured GFR (mGFR) versus estimated GFR (eGFR) calculated by 3 popular
      equations, 4-variable Modification of Diet in Renal Disease equation adjusted by
      Japanese correction coefficient (cmMDRD), 3-variable MDRD equation for Japanese
      population (eGFRcreat), and Chronic Kidney Disease-Epidemiology Collaboration
      equation adjusted by Japanese correction coefficient (cmCKD-EPI) in Japanese
      patients who had undergone RN or RNU due to renal cell carcinoma or upper tract
      urothelial carcinoma before and after surgery. RESULTS: Among the 3 equations
      examined, eGFRcreat was the closest to mGFR, although each eGFR was significantly
      higher than mGFR in the pre-operative period. In the post-operative period,
      cmMDRD and eGFRcreat, but not cmCKD-EPI, were comparable to mGFR. Each of eGFR
      was significantly correlated with mGFR in both the pre-operative and post
      operative periods. Similar results were obtained by the subanalysis of the
      patients with pre-operative mGFR of < 60 mL/min/1.73 m2. Results of kappa
      statistics also showed that eGFRcreat was most appropriate to estimate GFR both
      before and after heminephrectomy, when cut-off value of GFR of < 60 mL/min/1.73
      m2 was used. CONCLUSION: Results of the present study suggest that eGFRcreat is
      likely to be the most appropriate equation for patients undergoing RN or RNU due
      to urological malignancies. However, more precise equations will be required for
      accurately estimating GFR.

PMID- 29181661
TI  - Role of Sertoli and Leydig Cells in the Regulation of Spermatogonial Stem Cell
      and Development of Reproductive Disorders in Male C57Bl/6 Mice with Type 1
      Diabetes Mellitus.
AB  - Course administration streptozotocin to male C57Bl/6 mice induces a complex of
      symptoms typical of type 1 diabetes mellitus: hyperglycemia and insulin
      deficiency, focal inflammatory infiltration of the pancreas, destructive changes
      in the Langerhans islets, damage to the insular apparatus (reduced number of
      PDX1+ cells and insulin expression by the secreting cells). Male reproductive
      disorder are serious complications of type 1 diabetes mellitus. In "diabetic"
      mice, interstitial edema with inflammatory infiltration and microvascular
      disorders in the testicular tissue are observed, the number of endothelial
      precursors (CD45-/CD31+) and the total number and percentage of motile
      spermatozoa decreased, immature spermatogenic epithelium cells are desquamated of
      into the lumen of the tubules. Disturbances in the proliferation and
      differentiation of various spermatogonial stem cell populations (c-kit-/CD90+, c
      kit+/CD90+, and CD51-/CD24+/CD52+) in diabetes can be explained by the inhibitory
      influence of inflammatory factors on testosterone-producing Leydig cells.

PMID- 29181662
TI  - Inhibition of the Expression of Inducible NO Synthase by Neuroactive Amino Acid
      Derivatives Phenibut and Glufimet In Vitro and Ex Vivo.
AB  - The effects of glufimet and phenibut (glutamic acid and GABA derivatives,
      respectively) on concentration of inducible NO synthase and cGMP in LPS-activated
      mouse peritoneal macrophages and on NO end products in their culture medium were
      examined in vitro and ex vivo. Addition of LPS into culture medium elevated
      concentration of NO metabolites in this medium and increased concentration of
      inducible NO synthase and cGMP in the lysates of peritoneal macrophages, whereas
      incubation of the cells with examined agents applied at concentration of 10-5 M
      diminished these indices. Similar results were obtained with intraperitoneal
      injection of LPS, glufimet, and phenibut. In culture medium containing peritoneal
      macrophages from the mice injected with LPS (100 MUg/kg), the concentrations of
      inducible NO synthase and cGMP as well as the total concentration of nitrite and
      nitrate ions increased, whereas in culture medium with the cells from LPS-exposed
      mice treated with glufimet (28.7 mg/kg) and phenibut (50 mg/kg) these indices
      significantly decreased.

PMID- 29181663
TI  - Gene TNF Polymorphism -308G>A (rs1800629) and Its Relationship with the
      Efficiency of Ursodeoxycholic Acid Therapy in Patients with Nonalcoholic
      Stetohepatitis.
AB  - Association of TNF gene polymorphism -308G>A with the development of nonalcoholic
      steatohepatitis in the Russian population was revealed. Carriers of allele A of
      the TNF gene marker -308G>A have significantly higher risk of nonalcoholic
      steatohepatitis development: OR=1.69 (1.05; 2.71). Allele A carriage by this
      marker predicts an increase in the basal HDL level and a decrease in LDL and IL
      10 levels in the blood of healthy subjects. Patients with nonalcoholic
      steatohepatitis, differing by the TNF gene -308G>A marker genotype, differ by the
      time course of the markers of hepatocellular damage (ALT, AST), activity of
      hepatocyte apoptosis (tissue polypeptide-specific antigen), and activation of
      specific humoral immunity (gamma-globulin) in response to therapy with
      ursodeoxycholic acid in a dose of 10-15 mg/kg over 4-6 weeks. Carriers of allele
      A of the TNF gene polymorphic marker -308G>A are more sensitive to
      ursodeoxycholic acid therapy than carriers of GG genotype.

PMID- 29181664
TI  - Immunomorphological Changes in the Olfactory Bulbs of Rats after Intranasal
      Administration of Rotenone.
AB  - Changes in the structure of the olfactory bulbs after long-term intranasal
      administration of pesticide rotenone, a classical inductor of parkinsonism, to
      rats were studied by the methods of immunomorphology. In rats intranasally
      receiving rotenone in a dose of 2.5 mg/kg every other day over 2 weeks, a
      decrease in the density of dopaminergic neurons and the area of astrocyte
      processes in the olfactory bulbs, activation of microglia in the glomerular
      layer, and enhanced alpha-synuclein phosphorylation and its accumulation in the
      bodies of mitral layer neurons were observed. The observed changes agree with the
      hypothesis on pathological alpha-synuclein transport via the olfactory route in
      Parkinson's disease and confirm relevance of the rotenone model of Parkinson's
      disease for studies of the pathological accumulation of alpha-synuclein.

PMID- 29181665
TI  - Effect of Neoadjuvant Chemoradiation Therapy on Proteasome Pool in Rectal Cancer.
AB  - In untreated rectal cancer patients, the chymotrypsin-like activity of
      proteasomes in tumor tissue was 3-fold higher than that in conventionally normal
      tissue, which is explained by up-regulation of expression of immunoproteasomes
      and total pool of proteasomes. After neoadjuvant chemoradiation therapy,
      expressions of the total pool of proteasomes and immunoproteasomes in the tumor
      as well as the relative ratios of these indices to those in conventionally normal
      tissue were smaller by 1.4-3.3 times in comparison with the untreated patients.
      These changes were paralleled with pronounced (4.5-fold) down-regulation of
      proteasome activity in the tumor and a 3.7-fold decrease of activity ratio for
      the proteasomes in tumor and in conventionally normal tissue. The number of
      immunoproteasome subunits and the chymotrypsin-like activity of proteasomes can
      be viewed as potential markers to prognosticate effectiveness of neoadjuvant
      chemoradiation therapy in rectal cancer patients.

PMID- 29181666
TI  - Effects of Tripeptide Gly-His-Lys in Pain-Induced Aggressive-Defensive Behavior
      in Rats.
AB  - We studied the effect of Gly-His -Lys tripeptide administered intraperitoneally
      in doses of 5, 15, 50 and 150 MUg/kg on pain-induced aggressive-defensive
      behavior. A foot-shock model of aggression in rats grouped in pairs in an
      electrified chamber was used. Analgesic and antiaggresiogenic effects of the
      peptide were demonstrated. It was found the L-lysine residue plays the key role
      in these effects, because they were observed under the influence of L-lysine
      administration in doses close to its equimolar content in the studied tripeptide.

PMID- 29181667
TI  - Comparison of the Pharmacological Effects of Dimeric Dipeptide Nerve Growth
      Factor Mimetic GK-2 and Mexidol on the Model of Ischemic Stroke in Rats.
AB  - We compared the effects of GK-2 (dimeric dipeptide mimetic of nerve growth
      factor) and Mexidol (standard preparation for the therapy of stroke) on rat model
      of transient occlusion of the middle cerebral artery. GK-2 and Mexidol were
      administered intraperitoneally in the most active doses (1 and 100 mg/kg,
      respectively) 6 h after surgery and then once a day for 6 days. The preparations
      reduced the volume of cerebral infarction (by 60 and 30%, respectively). At the
      same time, GK-2 had a pronounced and statistically more reliable effect in a dose
      that is lower by two orders of magnitude. In addition, GK-2 significantly reduced
      the neurological deficit in the limb placement test, while Mexidol was
      ineffective in this test.

PMID- 29181668
TI  - Melatonin-Aluminum Oxide-Polymethylsiloxane Complex on Apoptosis of Liver Cells
      in a Model of Obesity and Type 2 Diabetes Mellitus.
AB  - We studied the effects of a melatonin-aluminum oxide-polymethylsiloxane complex
      (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver
      of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2
      diabetes. Complex M or placebo was administered daily through the gastric tube
      during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving
      placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and
      weak response for anti-apoptotic Bcl-2 protein were observed. Administration of
      complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression
      significantly increased and against the background of reduced Bad expression
      area. These findings attest to antiapoptotic effect of complex M in the liver on
      the model of type 2 diabetes mellitus.

PMID- 29181669
TI  - Inhibitory Effect of Interferons on Contractive Activity of Bovine Mesenteric
      Lymphatic Vessels and Nodes.
AB  - We studied the effect of IFNalpha-2b and IFNbeta-1a on phasic and tonic
      contractions of isolated bovine mesenteric lymphatic vessels and nodes. IFNalpha
      2b and IFNbeta-1a in concentrations of 250-1000 U/ml produced dose-dependent
      negative chronotropic and inotropic effects on spontaneous phasic contractions
      and tonus of lymphatic vessels and nodes. In de-endothelialized lymphatic vessels
      and nodes, IFNalpha-2b and IFNbeta-1a in the same concentrations had less
      pronounced inhibitory effect on spontaneous contraction and tonus. L-NAME (100
      MUM) and charybdotoxin (0.1 MUM with 0.5 MUM apamine) significantly attenuated
      the inhibitory effect of IFNalpha-2b on phasic and tonic contractions of lymph
      nodes. L-NAME (100 MUM) and indomethacin (10 MUM) significantly reduced the
      IFNalpha-2b-induced inhibitory effect on phasic and tonic contractions of lymph
      node. These results indicate that IFNalpha-2b and IFNbeta-1a have a pronounced
      inhibitory effect on the phasic and tonic contractions of bovine mesenteric
      lymphatic vessels and nodes. The responses are endothelium-dependent and are
      determined by production of NO and endothelium-dependent hyperpolarizing factor
      by endotheliocytes in lymphatic vessels and by production of NO and prostacyclin
      by endotheliocytes in the lymphatic nodes.

PMID- 29181670
TI  - Anticoagulant Effects of Arginine-Containing Peptides of the Glyproline Family
      (His-Phe-Arg-Trp-Pro-Gly-Pro and Thr-Lys-Pro-Arg-Pro-Gly-Pro) Revealed by
      Thromboelastography.
AB  - Thromboelastography revealed anticoagulant effects of 3 glyproline oligopeptides
      (in various concentrations): His-Phe-Arg-Trp-Pro-Gly-Pro, Thr-Lys-Pro-Arg-Pro-Gly
      Pro (Selank), and Pro-Gly-Pro. The parameters R, K, MA, S, TMA, and J changed to
      hypocoagulation direction in comparison to the control. At this, Selank
      demonstrated the maximal anticoagulation potency.

PMID- 29181671
TI  - Modifying Effect of Autotransfusion of Mesenchymal Stromal Cells on the
      Production of Reactive Oxygen Species and Cytokines by Mononuclear Cells in
      Patients with Chronic Heart Failure.
AB  - We studied in vivo modifying effect of autotransfusion of human bone marrow
      mesenchymal stromal cells on ROS generation and production of cytokines
      (TNFalpha,TNFbeta, IL-1alpha, IL-10, IFNgamma, and GM-CSF) and PGE2 by
      mononuclear cells of patients (N=21) with chronic heart failure. These parameters
      were evaluated prior to (control) and after (immediately and on day 14)
      intravenous administration of stromal cells in doses of 100-200*106. Immediately
      after autotransfusion, significant increase of in vitro zymosan-induced
      chemiluminescence of blood mononuclear cells from 10 patients was observed. At
      later terms after autotransfusion (day 14), inhibition of chemiluminescent
      activity of blood mononuclear cells was revealed in 50% patients. We discuss
      possible mechanisms of involvement of transplanted autologous bone marrow
      mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from
      the pro- to anti-inflammatory phenotype under conditions of their in vivo
      interaction manifesting in transition from activation to inhibition of ROS
      producing activity of macrophages and significant suppression of in vitro LPS
      induced production of TNFalpha and GM-CSF by blood mononuclears against the
      background of significantly elevated TNFbeta, IL-10, and IL-1alpha
      concentrations.

PMID- 29181672
TI  - Seasonal cycles of the TBE and Lyme borreliosis vector Ixodes ricinus modelled
      with time-lagged and interval-averaged predictors.
AB  - Ticks of the species Ixodes ricinus (L.) are the major vectors for tick-borne
      diseases in Europe. The aim of this study was to quantify the influence of
      environmental variables on the seasonal cycle of questing I. ricinus. Therefore,
      an 8-year time series of nymphal I. ricinus flagged at monthly intervals in
      Haselmuhl (Germany) was compiled. For the first time, cross correlation maps were
      applied to identify optimal associations between observed nymphal I. ricinus
      densities and time-lagged as well as temporal averaged explanatory variables. To
      prove the explanatory power of these associations, two Poisson regression models
      were generated. The first model simulates the ticks of the entire time series
      flagged per 100 m[Formula: see text], the second model the mean seasonal cycle.
      Explanatory variables comprise the temperature of the flagging month, the
      relative humidity averaged from the flagging month and 1 month prior to flagging,
      the temperature averaged over 4-6 months prior to the flagging event and the
      hunting statistics of the European hare from the preceding year. The first model
      explains 65% of the monthly tick variance and results in a root mean square error
      (RMSE) of 17 ticks per 100 m[Formula: see text]. The second model explains 96% of
      the tick variance. Again, the accuracy is expressed by the RMSE, which is 5 ticks
      per 100 m[Formula: see text]. As a major result, this study demonstrates that
      tick densities are higher correlated with time-lagged and temporal averaged
      variables than with contemporaneous explanatory variables, resulting in a better
      model performance.

PMID- 29181674
TI  - Morphological and molecular divergence of Rhipicephalus turanicus tick from
      Albania and China.
AB  - Rhipicephalus turanicus is an important tick species potentially carrying tick
      borne pathogens. Several tick species have obvious subspecies divergence. However
      few studies aimed to examine the existence of divergence within R. turanicus.
      Therefore, a detailed morphological and molecular analysis was conducted for
      comparing R. turanicus from the Mediterranean Basin (represented by Albania) and
      Central Asia (Northwestern China). Altogether 315 adult ticks of R. turanicus
      (103 from Albania and 212 from China) were morphologically and molecularly
      analysed. DNA samples were used for mitochondrial 16S rRNA and cox1 gene
      sequences analysis. In addition, as potentially genetic markers, three fragments
      including partial nad1-16S rRNA, nad2-cox1, cox1-tRNA-Lys, were designed and then
      phylogenetically analyzed. Based on detailed morphological observations, only
      basis capituli length:width ratio (females), the length, the width and the
      length:width ratio of the scutum (males) had differences between R. turanicus
      from China and Albania. Gene divergences of 16S rRNA, cox1, partial nad1-16S
      rRNA, nad2-cox1 and cox1-tRNA-Lys from China and Albania ticks were 3.53-4.84,
      3.57-4.92, 3.57-4.07, 3.57-4.39 and 3.18-4.69%, respectively. The evaluated five
      genetic markers revealed two phylogenetic branches in R. turanicus. Obvious
      differences exist within R. turanicus based on morphological and genetic
      analysis. Three newly designed genetic markers (partial nad1-16S rRNA, nad2-cox1
      and cox1-tRNA-Lys) in this study may be suitable genetic tools for identification
      and analysis in R. turanicus. Subspecies analysis of R. turanicus from other
      regions of the world should be initiated in the future.

PMID- 29181676
TI  - Can Vessel Invasion Change the TNM Stage in Non-small Cell Lung Cancer? A Reply.

PMID- 29181675
TI  - Toxicity of Juniperus oxycedrus oil constituents and related compounds and the
      efficacy of oil spray formulations to Dermatophagoides farinae (Acari:
      Pyroglyphidae).
AB  - The American house dust mite (AHDM), Dermatophagoides farinae Hughes (Acari:
      Pyroglyphidae), is recognized as an important source of allergens in the domestic
      environment. This study was conducted to determine whether 19 constituents from
      essential oil of cade, Juniperus oxycedrus L. (Cupressaceae), eight structurally
      related compounds, and another 16 previously known cade oil constituents were
      toxic for adult AHDMs and to determine the route of acaricidal action of the test
      compounds, as well as to assess the control efficacy of four experimental spray
      formulations containing the oil (10-40 mg/L sprays). In a fabric-circle contact
      mortality bioassay, methyleugenol (LD50, 5.82 ug/cm2) and guaiacol (8.24 ug/cm2)
      were the most toxic compounds against the mites, and the toxicity of these
      compounds and benzyl benzoate did not significantly differ. High toxicity was
      also observed with eugenol, m-cresol, and nerolidol (LD50, 12.52-19.52 ug/cm2),
      and these compounds were significantly more toxic than N,N-diethyl-3
      methylbenzamide (DEET) (LD50, 37.67 ug/cm2). Cade applied as 30 or 40 mg/L
      experimental sprays provided 96 and 100% mortality against the mites,
      respectively, whereas permethrin (cis:trans, 25:75) 2.5 g/L spray treatment
      resulted in 17% mortality. In vapor-phase mortality tests, the compounds
      described were consistently more toxic in closed versus open containers,
      indicating that toxicity was achieved mainly through the action of vapor.
      Reasonable mite control in indoor environments can be achieved by spray
      formulation containing the 40 mg/L cade oil as potential contact-action
      fumigants.

PMID- 29181677
TI  - Video-Assisted Thoracic Surgery for Patients with Advanced-Stage Non-small Cell
      Lung Cancer: A Reply.

PMID- 29181673
TI  - Relative transcription of autophagy-related genes in Amblyomma sculptum and
      Rhipicephalus microplus ticks.
AB  - Ticks endure stressful off-host periods and perform as vectors of a diversity of
      infectious agents, thus engaging pathways that expectedly demand for autophagy.
      Little is known of ticks' autophagy, a conserved eukaryotic machinery assisting
      in homeostasis processes that also participates in tissue-dependent metabolic
      functions. Here, the autophagy-related ATG4 (autophagin-1), ATG6 (beclin-1) and
      ATG8 (LC3) mRNAs from the human diseases vector Amblyomma sculptum and the cattle
      tick Rhipicephalus microplus were identified. Comparative qPCR quantifications
      evidenced different transcriptional status for the ATG genes in the salivary
      glands (SG), ovaries and intestines of actively feeding ticks. These ATGs had
      increased relative transcription under nutrient-deprivation, as determined by
      validation tests with R. microplus embryo-derivative cells BME26 and A. sculptum
      SG explants incubations in HBSS. Starvation lead to 4-31.8* and ~ 60-500*
      increments on the ATGs mRNA loads in BME26 and A. sculptum SG explants,
      respectively. PI3K inhibitor 3MA treatment also affected ATGs expression in
      BME26. Some ATGs were more transcribed in the SGs than in the ovaries of cattle
      ticks. Amblyomma sculptum/R. microplus interspecific comparisons showed that ATG4
      and ATG6 were 0.18* less expressed in A. sculptum SGs, but ~ 10-100* more
      expressed in their ovaries when compared to R. microplus organs. ATG4 and ATG8a
      transcript loads were ~ 120* and ~ 40* higher, respectively, in A. sculptum
      intestines when compared to cattle-ticks of similar weight category. ATGs
      expression in A. sculptum intestines increased with tick weight, indicating Atgs
      contribution to intracellular blood digestion. Possible roles of the autophagy
      machinery and their organ-specific expression profile on vector biology are
      discussed.

PMID- 29181678
TI  - Comment on: Pathologic Response to Preoperative Chemotherapy in Colorectal Liver
      Metastases: Fibrosis, Not Necrosis, Predicts Outcome.

PMID- 29181679
TI  - Impact of Neoadjuvant Chemotherapy on Nodal Disease and Nodal Surgery by Tumor
      Subtype.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) is known to downstage disease in the
      breast and increase breast conservation. It can also decrease nodal disease
      extent. We evaluated the impact of NAC on nodal positivity, nodal burden, and
      nodal surgery by tumor subtype. METHODS: All cT1-4c breast cancers from 2010 to
      2014 in the National Cancer Database were evaluated, comparing patients receiving
      NAC with those undergoing primary surgery (PS). Rates of pathologic node-negative
      status (pN0) and sentinel lymph node (SLN) surgery (1-5 nodes) were compared
      using chi-square tests, and adjusted odds ratios (OR) were estimated. RESULTS: Of
      461,549 patients, 36,715 (8.0%) received NAC and 424,834 (92.0%) had PS. In cN0
      patients, pN0 rates were higher in NAC compared with PS patients in ER-/HER2+
      [93.2 vs. 79.0%, odds ratio (OR) 3.64, p < 0.001], ER-/HER2- (89.9 vs. 85.2%, OR
      1.55, p < 0.001), and ER+/HER2+ (84.7 vs. 78.3%, OR 1.54, p < 0.001). Patients
      with cT2-3, N0 tumors had significantly higher rate of SLN surgery for NAC versus
      PS for each biologic subtype except for ER+/HER2- tumors, amongst which this was
      true only for T3 tumors. In cN1-3 patients, pN0 rates after NAC were 61.3% in ER
      /HER2+, 47.7% in ER+/HER2+, 47.3% in ER-/HER2-, and 20.2% in ER+/HER2- and SLN
      surgery was highest in ER-/HER2+ (28.9%, p < 0.05 versus other subtypes).
      CONCLUSION: NAC increases rates of pN0 among cN0 patients compared with PS. Among
      cN+ patients, 20-61% undergoing NAC convert to pN0 depending on tumor type, with
      lowest nodal response in ER+/HER2- disease. Use of NAC results in less extensive
      axillary surgery than in patients treated with PS in both cN0 and cN+ disease.

PMID- 29181680
TI  - The Impact of Primary Tumor Location on Long-Term Survival in Patients Undergoing
      Hepatic Resection for Metastatic Colon Cancer.
AB  - BACKGROUND: The impact of primary tumor location on overall survival (OS),
      recurrence-free survival (RFS), and long-term outcomes has not been well
      established in patients undergoing potentially curative resection of colorectal
      liver metastases (CRLM). METHODS: A single-institution database was queried for
      initial resections for CRLM 1992-2004. Primary tumor location determined by chart
      review (right = cecum to transverse; left = splenic flexure to sigmoid). Rectal
      cancer (distal 16 cm), multiple primaries, and unknown location were excluded.
      Kaplan-Meier and Cox regression methods were used. Cure was defined as actual 10
      year survival with either no recurrence or resected recurrence with at least 3
      years of disease-free follow-up. RESULTS: A total of 907 patients were included
      with a median follow-up of 11 years; 578 patients (64%) had left-sided and 329
      (36%) right-sided primaries. Median OS for patients with a left-sided primary was
      5.2 years (95% confidence interval [CI] 4.6-6.0) versus 3.6 years (95% CI 3.2
      4.2) for right-sided (p = 0.004). On multivariable analysis, the hazard ratio for
      right-sided tumors was 1.22 (95% CI 1.02-1.45, p = 0.028) after adjusting for
      common clinicopathologic factors. Median RFS was marginally different stratified
      by primary location (1.3 vs. 1.7 years; p = 0.065). On multivariable analysis,
      location of primary was not significantly associated with RFS (p = 0.105).
      Observed cure rates were 22% for left-sided and 20% for right-sided tumors.
      CONCLUSIONS: Among patients undergoing resection of CRLM, left-sided primary
      tumors were associated with improved median OS. However, long-term survival and
      recurrence-free survival were not significantly different stratified by primary
      location. Patients with left-sided primary tumors displayed a prolonged clinical
      course suggestive of more indolent biology.

PMID- 29181681
TI  - A Novel Preoperative Skeletal Muscle Measure as a Predictor of Postoperative
      Complications, Long-Term Survival and Tumor Recurrence for Patients with Gastric
      Cancer After Radical Gastrectomy.
AB  - BACKGROUND: Increasing numbers of studies have shown that skeletal muscle
      measures are closely associated with tumors. This study explored the relationship
      between skeletal muscle measures and short- and long-term outcomes after radical
      gastrectomy (RG) for gastric cancer (GC). METHODS: The study analyzed 221 GC
      patients who underwent RG between December 2009 and December 2010. The total
      psoas area (TPA) and psoas density [Hounsfield unit average calculation (HUAC)]
      were measured. The total psoas gauge (TPG) was created by multiplying TPA * HUAC.
      Low TPA, low HUAC, and low TPG were defined in the categorical analyses as the
      lowest quartile. Logistic regression modeling, the Kaplan-Meier method, and three
      step multivariate analysis were used. RESULTS: The median follow-up period was 64
      months. Compared with low TPA and low HUAC, only low TPG was an independent risk
      factor for postoperative complications. The univariate analysis showed that low
      TPA, low HUAC, and low TPG were predictors of overall survival (OS), recurrence
      free survival (RFS), and cancer-specific survival (CCS) after surgery. The result
      of the three-step multivariate analysis demonstrated that low TPG was an
      independent risk factor for OS, RFS, and CCS. Moreover, the prognostic value of
      TPG was superior to that of TPA and HUAC. The patients with low TPG experienced
      significantly more postoperative liver recurrence than the patients with high TPG
      (p = 0.011). CONCLUSION: Compared with preoperative skeletal muscle quantity
      (TPA) and quality (HUAC), TPG can more accurately predict complications and
      prognosis after RG. In addition, TPG may be an indicator for the early detection
      of liver recurrence after RG.

PMID- 29181682
TI  - Effectiveness of Hepatic Artery Infusion (HAI) Versus Selective Internal
      Radiation Therapy (Y90) for Pretreated Isolated Unresectable Colorectal Liver
      Metastases (IU-CRCLM).
AB  - BACKGROUND: In the era of modern effective systemic chemotherapy, the comparative
      effectiveness of hepatic artery infusion (HAI) versus selective internal
      radiation therapy (yttrium-90 [Y90]) for pretreated patients with isolated
      unresectable colorectal liver metastasis (IU-CRCLM) remains unknown. This study
      sought to compare the overall survival (OS) after HAI versus Y90 for IU-CRCLM
      patients treated with modern chemotherapy and to perform a cost analysis of both
      regional methods. METHODS: This study retrospectively reviewed patients receiving
      HAI or Y90 in combination with modern chemotherapy as second-line therapy for IU
      CRCLM. Overall survival was calculated from the time of IU-CRCLM diagnosis. Uni-
      and multivariate models were constructed to identify independent predictors of
      survival. RESULTS: The inclusion criteria were met by 97 patients (48 HAI
      patients and 49 Y90 patients). Both groups were similar in terms of age, gender,
      body mass index (BMI), synchronous disease, carcinoembryonic antigen (CEA), liver
      tumor burden, and chemotherapy-related characteristics including use of biologics
      and lines of chemotherapy (all p > 0.05). The HAI group had a better OS than the
      Y90 group (31.2 vs. 16.3 months; p < 0.001). A trend toward reduced cost favored
      the HAI group (median, $29,479 vs. $39,092; p = 0.296). The multivariate analysis
      showed that receipt of HAI (hazard ratio 0.465) and number of chemotherapy lines
      (HR 0.797) were associated with improved OS from the date of IU-CRCLM diagnosis.
      CONCLUSIONS: This is the first study to evaluate the comparative effectiveness of
      HAI versus Y90 in the era of modern chemotherapy, and the findings suggests that
      HAI is associated with better survival than Y90 for patients with pretreated IU
      CRCLM.

PMID- 29181683
TI  - Analysis of the Infiltrative Features of Chordoma: The Relationship Between Micro
      Skip Metastasis and Postoperative Outcomes.
AB  - BACKGROUND: Chordomas are very rare primary malignant bone tumors that arise
      commonly from the sacrum (50-60%) and clivus (25-35%). Chordomas have a high rate
      of recurrence. The authors confirmed a unique histologic infiltration pattern of
      chordomas that resembles a skip-metastatic lesion in normal tissue around tumor,
      which they named "micro-skip metastasis." This study aimed to examine the
      correlations between the clinicopathologic features of chordomas, including micro
      skip metastasis, and the clinical outcomes, including overall survival, local
      recurrence-free survival, and distant metastasis-free survival. METHODS: The
      study analyzed histopathologic and clinical data from patients with sacral
      chordomas who underwent en bloc resection from July 1991 through July 2014. Cases
      with a minimum follow-up period shorter than 20 months after resection were
      excluded. Kaplan-Meier survival analyses with log-rank tests were performed for
      overall survival, metastasis-free survival, and recurrence-free survival.
      RESULTS: The study retrospectively reviewed 40 patients. The mean follow-up
      period was 98.2 months (range 22-297 months). The local recurrence rate was
      41.3%. Micro-skip metastases, observed in 17 patients (42.5%), were associated
      with a significantly increased risk of local recurrence (p = 0.023) but not with
      overall survival or distant metastasis-free survival. Poorer overall survival was
      associated with histologic vascular invasion (p = 0.030) and a greater maximum
      tumor diameter (p = 0.050). CONCLUSIONS: The presence of micro-skip metastasis
      was associated with a higher rate of local recurrence. The maximum tumor diameter
      and the presence of histologic vascular invasion were associated with poorer
      overall survival.

PMID- 29181684
TI  - Amputation for Sarcoma: Revisiting a 19th Century Treatment in the 21st Century.

PMID- 29181685
TI  - Correction to: Statistical crossover and nonextensive behavior of neuronal short
      term depression.
AB  - The authors apologize for the following errors published in the article. However,
      these errors do not modify the main assumptions in our work nor affects the
      discussion (interpretation) of the results.

PMID- 29181686
TI  - Administration of a Sol-Gel Formulation of Phenylephrine Using Low-Temperature
      Hollow Microneedle for Treatment of Intermittent Fecal Incontinence.
AB  - PURPOSE: A low temperature hollow microneedle system was devised to deliver sol
      gel transition formulation near the surface of the skin for extended release and
      local delivery of drug by a non-invasive method. This new system can improve
      treatment of intermittent fecal incontinence. METHOD: The low-temperature system
      was integrated with a hollow microneedle to maintain the low temperature of the
      sol formulation. Various sol-gel formulations using Pluronic F-127 (PF-127) and
      Hydroxy-propyl-methyl-cellulose (HPMC) were prepared, and their gelation
      temperature, flow property, and diffusion retardation were observed. Resting anal
      sphincter pressure in response to a phenylephrine (PE) sol-gel formulation was
      measured using an air-charged catheter. The biocompatibility of the sol-gel PE
      formulation was evaluated by observing the immunological response. RESULTS: When
      the PF-127 25%, HPMC 1% and PE formulation (PF25-HPMC1-PE) was injected through
      the peri-anal skin of the rat in vivo, the highest pressure on the anal sphincter
      muscle occurred at 6-8 h and anal pressure increased and lasted twice as long as
      with the phosphate-buffered saline (PBS)-PE formulation. There was no significant
      difference in the number of mast cells after administration into the rat in vivo
      between the PF25-HPMC1-PE formulation and the PBS-PE formulation. CONCLUSION: The
      combination of a low-pain hollow microneedle system and an injectable sol-gel
      formulation improved the efficacy of treatment of intermittent fecal
      incontinence. A low-temperature hollow microneedle system using a sol-gel
      formulation has many applications in medical treatments that require depot
      effect, local targeting, and pain control.

PMID- 29181687
TI  - miR-542-3p Appended Sorafenib/All-trans Retinoic Acid (ATRA)-Loaded Lipid
      Nanoparticles to Enhance the Anticancer Efficacy in Gastric Cancers.
AB  - PURPOSE: In this study, miR-542-3p appended SRF/ATRA-loaded solid lipid
      nanoparticle was successfully prepared and demonstrated for its therapeutic
      efficacy against gastric cancers. METHODS: The particles were nanosized and
      typically spherical in shape. In vitro release study showed that release of ATRA
      was significantly slower compared to that of SRF from the NPs. RESULTS: MTT assay
      showed that miR-542-3p have a strong inhibitory effect on the proliferation of
      MGC-803 cancer cells in a typical dose dependent manner. Nanocarrier
      encapsulation of SRF + ATRA induced a significantly higher cytotoxic effect
      compared to either individual drug or cocktail combinations indicating that the
      cellular uptake of different formulations was rate limiting factor in the
      therapeutic efficacy. Importantly, miR-542-3p-based miSRNP exhibited an extremely
      significant toxic effect compared to any other treated group. Importantly, miSRNP
      induced a significantly higher early (~55%) and late (~15%) apoptotic effect in
      gastric cancer cells. In vivo anticancer analysis results clearly suggest that
      nanoparticle encapsulation of combination of SRF and miRNA (with miRNA) will have
      greater antitumor efficacy in tumor mice. CONCLUSION: Overall, unique combination
      of miRNA coupled with SRF + ATRA in a lipid nanocarrier could be a promising
      therapeutic approach in gastric cancer treatment.

PMID- 29181688
TI  - Expanded description of Lamproglena cleopatra Humes, 1957 (Lernaeidae: Copepoda)
      from Labeo spp. (Cyprinidae) with a key to species of Lamproglena von Nordmann,
      1832.
AB  - The occurrence of the copepod Lamproglena cleopatra Humes, 1957, parasitising
      freshwater fishes in the Limpopo River System is presented, along with new
      morphological data. This crustacean was originally described parasitising a
      cyprinid (Labeo forskalii Ruppell) from the River Nile, Egypt. During 2014-2015
      crustacean samples were collected from the gills of three cyprinid fish species,
      Labeo rosae Steindachner from Flag Boshielo Dam, Labeo molybdinus Du Plessis from
      Nwanedi-Luphephe Dam in South Africa, and Labeo ruddi Boulenger from the River
      Bubye in Zimbabwe. The specimens from the present study were morphologically
      similar regardless of the host, but exhibited some morphometric intraspecific
      differences in comparison with the type-specimen from Egypt. A description of L.
      cleopatra copepodid III stage and a taxonomic key to Lamproglena spp. is
      provided.

PMID- 29181689
TI  - Do Parents and Clinicians Agree on Ratings of Autism-Related Behaviors at 12
      Months of Age? A Study of Infants at High and Low Risk for ASD.
AB  - Given the emphasis on early screening for ASD, it is crucial to examine the
      concordance between parent report and clinician observation of autism-related
      behaviors. Similar items were compared from the First Year Inventory (Baranek et
      al. First-Year Inventory (FYI) 2.0. University of North Carolina, Chapel Hill,
      2003), a parent screener for ASD, and the ADOS-2 Toddler Module (Lord et al.
      2013), a standardized ASD diagnostic tool. Measures were administered
      concurrently to 12-month-olds at high and low risk for ASD. Results suggest that
      clinicians and parents rated behaviors similarly. In addition, both informants
      rated high-risk infants as more impaired in several social-communication
      behaviors. Furthermore, the format of questions impacted agreement across
      observers. These findings have implications for the development of a new
      generation of screening instruments for ASD.

PMID- 29181690
TI  - Association of maternal depression with dietary intake, growth, and development
      of preterm infants: a cohort study in Beijing, China.
AB  - This study aimed to explore the association of maternal depression with nutrient
      intake, growth, and development of preterm infants. A cohort study of 201 infants
      was conducted in Beijing. Based on the gestational age of an infant and status of
      the mother, the infants were divided into four groups: non-depression-fullterm
      (64), non-depression-preterm (70), depression-fullterm (36), and depression
      preterm (31). Data on sociodemographic characteristics, nutritional intake,
      growth, and developmental status of children at 8 months (corrected ages) were
      collected using a quantitative questionnaire, a 24-Hour Dietary Recall,
      anthropometric measurements, and the Bayley-III scale. A multivariate analysis
      was used to evaluate the effects of maternal depression and preterm birth on
      infant growth and development. The energy, protein, and carbohydrate intake in
      the depression group was lower than the recommended amounts. The depression
      preterm groups indicated the lowest Z-scores for length and weight and the lowest
      Bayley-III scores. Preterm infants of depressed mothers are at high risks of poor
      growth and development delay.

PMID- 29181691
TI  - Irreversible phenotypic perturbation and functional impairment of B cells during
      HIV-1 infection.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection can damage humoral
      immunity. The knowledge of B cell perturbations during chronic HIV-1 infection
      and their recovery after combined antiretroviral therapy (cART) is not complete
      yet, and thus attempts to further improve humoral immunity are impeded. In this
      study, an HIV-1 chronically infected cohort with similar demographics, infection
      history, genetic background, and HIV-1 genotype was established to probe B cell
      perturbations. Results showed that the B cells from this cohort were highly
      activated and prone to cell death, and B cell compartments were altered
      significantly. Notably, although cART partially reversed the hyperactivation and
      reduced tissue-like memory B cells, other B cell perturbations, including
      impaired expression of survival factor Bcl-2, costimulatory molecules, and
      shrunken resting memory B cells, were irreversible. Further functional
      characterization revealed that the influenza HAspecific antibody-secreting cells
      were significantly lower during HIV-1 infection, whereas the recalled antibody
      response to HIV-1-specific antigens was decreased after cART. Finally, CpG plus
      R848 treatment increased the survival of B cells and memory B cells in vitro from
      HIV-1-infected patients. In conclusion, this study identified irreversible B cell
      immune perturbations in chronic HIV-1 infections regardless of cART and proposed
      the potential strategy to enhance B cell functions through the improvement of
      cell survival.

PMID- 29181692
TI  - Serum metabolites and risk of myocardial infarction and ischemic stroke: a
      targeted metabolomic approach in two German prospective cohorts.
AB  - Metabolomic approaches in prospective cohorts may offer a unique snapshot into
      early metabolic perturbations that are associated with a higher risk of
      cardiovascular diseases (CVD) in healthy people. We investigated the association
      of 105 serum metabolites, including acylcarnitines, amino acids, phospholipids
      and hexose, with risk of myocardial infarction (MI) and ischemic stroke in the
      European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam
      (27,548 adults) and Heidelberg (25,540 adults) cohorts. Using case-cohort
      designs, we measured metabolites among individuals who were free of CVD and
      diabetes at blood draw but developed MI (n = 204 and n = 228) or stroke (n = 147
      and n = 121) during follow-up (mean, 7.8 and 7.3 years) and among randomly drawn
      subcohorts (n = 2214 and n = 770). We used Cox regression analysis and combined
      results using meta-analysis. Independent of classical CVD risk factors, ten
      metabolites were associated with risk of MI in both cohorts, including
      sphingomyelins, diacyl-phosphatidylcholines and acyl-alkyl-phosphatidylcholines
      with pooled relative risks in the range of 1.21-1.40 per one standard deviation
      increase in metabolite concentrations. The metabolites showed positive
      correlations with total- and LDL-cholesterol (r ranged from 0.13 to 0.57). When
      additionally adjusting for total-, LDL- and HDL-cholesterol, triglycerides and C
      reactive protein, acyl-alkyl-phosphatidylcholine C36:3 and diacyl
      phosphatidylcholines C38:3 and C40:4 remained associated with risk of MI. When
      added to classical CVD risk models these metabolites further improved CVD
      prediction (c-statistics increased from 0.8365 to 0.8384 in EPIC-Potsdam and from
      0.8344 to 0.8378 in EPIC-Heidelberg). None of the metabolites was consistently
      associated with stroke risk. Alterations in sphingomyelin and phosphatidylcholine
      metabolism, and particularly metabolites of the arachidonic acid pathway are
      independently associated with risk of MI in healthy adults.

PMID- 29181693
TI  - Cost-effectiveness analysis of patient self-testing therapy of oral
      anticoagulation.
AB  - Patient Self-testing (PST) could be an option for present anticoagulation therapy
      monitoring, but current evidence on its cost-effectiveness is limited. This study
      aims to estimate the cost-effectiveness of PST to other different care approaches
      for anticoagulation therapy in Thailand, a low-to-middle income country (LMIC). A
      Markov model was used to compare lifetime costs and quality-adjusted life years
      (QALYs) accrued to patients receiving warfarin through PST or either
      anticoagulation clinic (AC) or usual care (UC). The model was populated with
      relevant information from literature, network meta-analysis, and database
      analyses. Incremental cost-effectiveness ratios (ICERs) were presented as the
      year 2015 values. A base-case analysis was performed for patients at age 45-year
      old. Sensitivity analyses including one-way and probabilistic sensitivity
      analyses (PSA) were constructed to determine the robustness of the findings. From
      societal perspective, PST increased QALY by 0.87 and costs by 112,461 THB
      compared with UC. Compared with AC, PST increased QALY by 0.161 and costs by
      21,019 THB. The ICER with PST was 128,697 (3625 USD) and 130,493 THB (3676 USD)
      per QALY gained compared with UC and AC, respectively. The probability of PST
      being cost-effective is 74.1% and 51.9%, compared to UC and AC, respectively, in
      Thai context. Results were sensitive to the efficacy of PST, age and frequency of
      hospital visit or self-testing. This analysis suggested that PST is highly cost
      effective compared with usual care and less cost-effective against
      anticoagulation clinic. Patient self-testing strategy appears to be economically
      valuable to include into healthcare system within the LMIC context.

PMID- 29181695
TI  - MEMRI reveals altered activity in brain regions associated with anxiety,
      locomotion, and cardiovascular reactivity on the elevated plus maze in the WKY vs
      SHR rats.
AB  - Individuals with anxiety/depression often have exaggerated cardiovascular
      responses to stressful stimuli and a comorbidity with hypertension.
      Alternatively, individuals with hypertension can be more anxious. In the present
      study cardiovascular changes were evaluated during behavioral testing of anxious
      behavior on the elevated plus maze (EPM) in the spontaneously hypertensive rat
      (SHR), a rodent model of neurogenic hypertension, and compared to the response of
      the more anxious, but normotensive, Wistar-Kyoto rat (WKY). Manganese-enhanced
      magnetic resonance imaging (MEMRI) was used to identify regional differences in
      baseline brain activity. Parallel to indicators of elevated behavioral anxiety on
      the EPM, WKYs had a greater increase in blood pressure but not heart rate when
      compared to the SHR while on the EPM. Associated with differences in anxiety
      related behavior and autonomic responses, we observed increased baseline activity
      in the amygdala, central gray, habenula and interpeduncular nucleus with MEMRI of
      the WKY compared to the SHR. Conversely, elevated baseline brain activity was
      found in regions associated with blood pressure control and system arousal,
      including the hypothalamus, locus coeruleus and pedunculopontine tegmental
      nucleus, in the SHR vs WKY, in-line with increased resting blood pressure and
      increased mobility in this strain. Lastly, reduced activity in hippocampal
      regions was identified in the SHR compared to the WKY and may be associated with
      cognitive impairment previously reported in the SHR. Thus, autonomic reactivity
      may be a true measure of stress in rodent models of anxiety and MEMRI presents a
      powerful technique to uncover novel brain mechanisms of blood pressure control.

PMID- 29181694
TI  - Infection prevention and control in ultrasound - best practice recommendations
      from the European Society of Radiology Ultrasound Working Group.
AB  - OBJECTIVES: The objective of these recommendations is to highlight the importance
      of infection prevention and control in ultrasound (US), including diagnostic and
      interventional settings. METHODS: Review of available publications and discussion
      within a multidisciplinary group consistent of radiologists and microbiologists,
      in consultation with European patient and industry representatives.
      RECOMMENDATIONS: Good basic hygiene standards are essential. All US equipment
      must be approved prior to first use, including hand held devices. Any equipment
      in direct patient contact must be cleaned and disinfected prior to first use and
      after every examination. Regular deep cleaning of the entire US machine and
      environment should be undertaken. Faulty transducers should not be used. As
      outlined in presented flowcharts, low level disinfection is sufficient for
      standard US on intact skin. For all other minor and major interventional
      procedures as well as all endo-cavity US, high level disinfection is mandatory.
      Dedicated transducer covers must be used when transducers are in contact with
      mucous membranes or body fluids and sterile gel should be used inside and outside
      covers. CONCLUSIONS: Good standards of basic hygiene and thorough decontamination
      of all US equipment as well as appropriate use of US gel and transducer covers
      are essential to keep patients safe. MAIN MESSAGES: * Transducers must be
      cleaned/disinfected before first use and after every examination. * Low level
      disinfection is sufficient for standard US on intact skin. * High level
      disinfection is mandatory for endo-cavity US and all interventions. * Dedicated
      transducer covers must be used for endo-cavity US and all interventions. *
      Sterile gel should be used for all endo-cavity US and all interventions.

PMID- 29181696
TI  - Comparison of clinical remission and survival between CLAG and FLAG induction
      chemotherapy in patients with refractory or relapsed acute myeloid leukemia: a
      prospective cohort study.
AB  - PURPOSE: To compare the clinical remission and survival between CLAG and FLAG
      induction chemotherapy in treating patients with refractory or relapsed acute
      myeloid leukemia (R/R AML). METHODS: 103 R/R AML patients were consecutively
      enrolled in this prospective cohort study. 55 patients were treated by CLAG
      induction chemotherapy as follows: 5 mg/m2/day cladribine (days 1-5); 2 g/m2/day
      cytarabine (days 1-5) and 300 MUg/day filgrastim (days 0-5). While 48 patients
      were treated by FLAG: 30 mg/m2/day fludarabine (days 1-5), 2 g/m2/day cytarabine
      (days 1-5), and 300 MUg/day filgrastim (days 0-5). RESULTS: CLAG induction
      chemotherapy achieved 61.7% complete remission rate (CR) and 78.7% overall
      remission rate (ORR), which was similar with FLAG chemotherapy which realized
      48.7% CR and 69.2% ORR. No difference of overall survival (OS) was discovered
      between two groups either. Age cytarabine 60 years, secondary disease, poor risk
      stratification and BM blast >= 42.7% and second or higher salvage therapy were
      independent factors for worse prognosis. Subgroups analysis revealed that in
      patients with second or higher salvage therapy, CLAG seemed to achieve a higher
      CR than FLAG. And in patients with relapsed disease, poor risk stratification or
      CR at first induction, CLAG seemed to realize a prolonged OS compared to FLAG.
      CONCLUSION: CLAG was equally effective to FLAG induction chemotherapy in total
      R/R AML patients, while CLAG seemed to be a better option than FLAG in patients
      with relapsed disease, poor risk stratification, CR at first induction or second
      or higher salvage therapies.

PMID- 29181697
TI  - Kernel-Based Visual Hazard Comparison (kbVHC): a Simulation-Free Diagnostic for
      Parametric Repeated Time-to-Event Models.
AB  - Repeated time-to-event (RTTE) models are the preferred method to characterize the
      repeated occurrence of clinical events. Commonly used diagnostics for parametric
      RTTE models require representative simulations, which may be difficult to
      generate in situations with dose titration or informative dropout. Here, we
      present a novel simulation-free diagnostic tool for parametric RTTE models; the
      kernel-based visual hazard comparison (kbVHC). The kbVHC aims to evaluate whether
      the mean predicted hazard rate of a parametric RTTE model is an adequate
      approximation of the true hazard rate. Because the true hazard rate cannot be
      directly observed, the predicted hazard is compared to a non-parametric kernel
      estimator of the hazard rate. With the degree of smoothing of the kernel
      estimator being determined by its bandwidth, the local kernel bandwidth is set to
      the lowest value that results in a bootstrap coefficient of variation (CV) of the
      hazard rate that is equal to or lower than a user-defined target value
      (CVtarget). The kbVHC was evaluated in simulated scenarios with different number
      of subjects, hazard rates, CVtarget values, and hazard models (Weibull, Gompertz,
      and circadian-varying hazard). The kbVHC was able to distinguish between Weibull
      and Gompertz hazard models, even when the hazard rate was relatively low (< 2
      events per subject). Additionally, it was more sensitive than the Kaplan-Meier
      VPC to detect circadian variation of the hazard rate. An additional useful
      feature of the kernel estimator is that it can be generated prior to model
      development to explore the shape of the hazard rate function.

PMID- 29181699
TI  - Benefits, benefits, once more benefits... with no risk? Stop overlooking the
      harms of medicines.
AB  - Consideration of drug benefits and harms is asymmetric. Approval of drugs is
      mainly based on efficacy, while the assessment of their safety is left to post
      marketing commitments or spontaneous reporting. Benefits are overestimated as a
      result of pharmaceutical companies' advertisements, the paucity of independent
      information, and the scant understanding of the effectiveness of medicines in
      real life. Polypharmacy in older adults-even during the last period of their life
      reflects the tendency to assign priority to efficacy and overlook harms, although
      nobody knows what happens when three or more drugs are given chronically. Medical
      journals and public research funding projects do not pay enough attention to drug
      toxicity. We call for a sense of purpose by all those involved in medicine to
      tackle this problem. European and national agencies and health authorities should
      promote and support independent information and experimental and clinical studies
      on drug toxicity. Information should rely not just on spontaneous reporting but
      also on active pharmacovigilance. The benefit-harm profile of drugs should be
      periodically reviewed in the light of toxic effects that come to light over the
      years. Potential interactions within polytherapies should be sought by re
      assessing the pharmacokinetics and pharmacodynamics of their components.

PMID- 29181700
TI  - Correction to: Effect of sertraline on complications and survival after
      hematopoietic stem-cell transplantation, a double-blind, placebo-controlled
      clinical study.
AB  - The correct name of the corresponding author should be ''Maryam Mehrpooya'', and
      not ''Mehrpooya Maryam'' as given in the original publication of the article.

PMID- 29181698
TI  - Pharmacokinetics of CYP2C9, CYP2C19, and CYP2D6 substrates in healthy Chinese and
      European subjects.
AB  - PURPOSE: The aim of this analysis is to compare the pharmacokinetics of drug
      substrates in healthy Chinese and European subjects of aligned CYP2C9, CYP2C19,
      or CYP2D6 enzyme activity, providing further insight into drivers of interethnic
      differences in pharmacokinetics. METHODS: Following identification of appropriate
      drug substrates, a comprehensive and structured literature search was conducted
      to identify single-dose pharmacokinetic data in healthy Chinese or European
      subjects with reported CYP2C9, CYP2C19, or CYP2D6 activity (genotype or
      phenotype). The ratio of drug AUC in the Chinese and European subjects classified
      with aligned enzyme activity was calculated (ethnicity ratio (ER)). RESULTS: For
      22/25 drugs identified, the ERs calculated indicated no or only limited
      interethnic differences in exposure (<twofold) in Chinese and European subjects
      with aligned polymorphic enzyme activity. The interethnic differences observed
      can reflect differences across populations in additional determinants of
      pharmacokinetics, although the notable between study variation and change over
      time in methods used to assign enzyme activity may also be contributing factors.
      There was no association between drug substrate fraction metabolized (fm) for
      CYP2C9, CYP2C19, or CYP2D6 and the ERs calculated. CONCLUSION: The spectrum of
      pharmacokinetic determinants for each drug substrate and their differences across
      ethnic groups must be considered on a case-by-case basis in addition to
      metabolism by CYP2C9, CYP2C19, or CYP2D6. This analysis has also highlighted the
      challenges which arise when comparing published datasets if consistent methods to
      assign polymorphic enzyme activity have not been used.

PMID- 29181701
TI  - Non-alcoholic steatohepatitis induced by induction chemotherapy for pediatric
      acute lymphoblastic leukemia.

PMID- 29181703
TI  - Transcatheter MitraClip implantation facilitated by transthoracic
      echocardiography.

PMID- 29181704
TI  - Correction to: Protein phosphatases 1 and 2A and their naturally occurring
      inhibitors: current topics in smooth muscle physiology and chemical biology.
AB  - The article Protein phosphatases 1 and 2A and their naturally occurring
      inhibitors: current topics in smooth muscle physiology and chemical biology,
      written by Akira Takai, Masumi Eto, Katsuya Hirano, Kosuke Takeya, Toshiyuki
      Wakimoto and Masaru Watanabe, was originally published electronically on the
      publisher's internet portal (currently SpringerLink) on 5th July 2017 without
      open access.

PMID- 29181702
TI  - Geoepidemiology of Primary Biliary Cholangitis: Lessons from Switzerland.
AB  - : No data on primary biliary cholangitis (PBC) are available in Switzerland. We
      established a national patient cohort to obtain information on PBC phenotypes and
      disease course in Switzerland. Local databases in all university hospitals and in
      two large secondary centers were searched for case finding. In addition, all
      primary care physicians, gastroenterologists, rheumatologists, and dermatologists
      were invited to contribute patients from their own medical records. PBC diagnosis
      was centrally reviewed. Five hundred one PBC patients were identified, 474 were
      included in data analysis, and 449 of them were enrolled by tertiary centers. The
      catchment area accounts for approximately one third of the Swiss population or
      approximately 2.8 million inhabitants. The median age at diagnosis was 53 years,
      84% were women, and 86% were anti-mitochondrial antibody positive. The median
      follow-up was 5.4 years, 12.6% experienced a liver-related endpoint. Splenomegaly
      was present at diagnosis in one quarter of patients and in half of male patients.
      Approximately one third were non-responders to ursodeoxycholic acid (UDCA). The
      median transplant-free survival at 10 years was 85%. The following variables were
      independently associated with poor outcome: low platelet count at baseline (HR =
      0.99, p < 0.0001), elevated alkaline phosphatase at baseline (HR = 1.36, p <
      0.0001), elevated bilirubin at baseline (HR = 1.11, p = 0.001), and elevated
      alanine aminotransaminase (HR = 1.35, p = 0.04) after 12 months of UDCA therapy.
      The AUROC for the UK-PBC risk score at 5, 10, and 15 years was 0.82. The AUROC
      for the Globe score at 5, 10, and 15 years was 0.77. Patients included in this
      study are currently being enrolled in a prospective nationwide registry with
      biobank, taking advantage of the collaboration network generated by this study.
      Our study provides the first snapshot of PBC in Switzerland, describing a
      diagnostic delay with one quarter of patients diagnosed when already in the
      cirrhotic stage. We were also able to externally validate the UK-PBC risk score
      and the Globe score. The ongoing nationwide prospective registry will be
      fundamental to improve disease awareness and interdisciplinary collaborations and
      will serve as a platform for clinical and translational research. TRIAL
      REGISTRATION NUMBER: clinicaltrials.gov : NCT02846896; SNCTP000001870.

PMID- 29181705
TI  - Coenzyme Q10-Loaded Fish Oil-Based Bigel System: Probing the Delivery Across
      Porcine Skin and Possible Interaction with Fish Oil Fatty Acids.
AB  - Coenzyme Q10 (CoQ10) is a vitamin-like oil-soluble molecule that has anti-oxidant
      and anti-ageing effects. To determine the most optimal CoQ10 delivery vehicle,
      CoQ10 was solubilised in both water and fish oil, and formulated into hydrogel,
      oleogel and bigel. Permeability of CoQ10 from each formulation across porcine ear
      skin was then evaluated. Furthermore, the effects of the omega-3 fatty
      eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from fish oil on skin
      permeation were investigated by means of nuclear magnetic resonance (NMR) and
      computerised molecular modelling docking experiments. The highest drug permeation
      was achieved with the bigel formulation that proved to be the most effective
      vehicle in delivering CoQ10 across the skin membrane due to a combination of its
      adhesive, viscous and lipophilic properties. Furthermore, the interactions
      between CoQ10 and fatty acids revealed by NMR and molecular modelling experiments
      likely accounted for skin permeability of CoQ10. NMR data showed dose-dependent
      changes in proton chemical shifts in EPA and DHA. Molecular modelling revealed
      complex formation and large binding energies between fatty acids and CoQ10. This
      study advances the knowledge about bigels as drug delivery vehicles and
      highlights the use of NMR and molecular docking studies for the prediction of the
      influence of drug-excipient relationships at the molecular level.

PMID- 29181706
TI  - Self-Assembling Raloxifene Loaded Mixed Micelles: Formulation Optimization, In
      Vitro Cytotoxicity and In Vivo Pharmacokinetics.
AB  - Raloxifene (RLX) has been strongly recommended for postmenopausal women at high
      risk of invasive breast cancer and for prevention of osteoporosis. However, low
      aqueous solubility and reduced bioavailability hinder its clinical application.
      The objective of this study was to explore the potential of RLX loaded mixed
      micelles (RLX-MM) using Pluronic F68 and Gelucire 44/14 for enhanced
      bioavailability and improved anticancer activity on human breast cancer cell line
      (MCF-7). RLX-MM were prepared by solvent evaporation method and optimized using
      32 factorial design. The average size, entrapment efficiency and zeta potential
      of the optimized formulation were found to be 190 +/- 3.3 nm, 79 +/- 1.3%, 13 +/-
      0.8 mV, respectively. In vitro study demonstrated 74.68% drug release from RLX-MM
      in comparison to 42.49% drug release from RLX dispersion. According to the in
      vitro cytotoxicity assay, GI50 values on MCF-7 breast cancer cell line for RLX-MM
      and free RLX were found to be 22.5 and 94.71 MUg/mL, respectively. Significant
      improvement (P < 0.05) in the anticancer activity on MCF-7 cell line was observed
      in RLX-MM over RLX pure drug. Additionally, oral bioavailability of RLX-MM was
      improved by 1.5-fold over free RLX when administered in female Wistar rats.
      Incorporation of RLX in the hydrophobic core and improved solubility of the drug
      due to hydrophilic shell attributed to the enhanced cytotoxicity and
      bioavailability of RLX-MM. This research establishes the potential of RLX loaded
      mixed micelles of Pluronic F68 and Gelucire 44/14 for improved bioavailability
      and anticancer activity on MCF-7 cell line.

PMID- 29181708
TI  - [Health: regional focus].

PMID- 29181707
TI  - Role of Sex and the Environment in Moderating Weight Gain Due to Inadequate
      Sleep.
AB  - PURPOSE OF REVIEW: The growing prevalence of obesity, inadequate sleep and sleep
      disorders together with the negative impact of lack of sleep on overall health
      highlights the need for therapies targeted towards weight gain due to sleep loss.
      RECENT FINDINGS: Sex disparities in obesity and sleep disorders are present; yet,
      the role of sex is inadequately addressed and thus it is unclear whether
      sensitivity to sleep disruption differs between men and women. Like sex,
      environmental factors contribute to the development of obesity and poor sleep.
      The obesogenic environment is characterized by easy access to palatable foods and
      a low demand for energy expenditure in daily activities. These and other
      environmental factors are discussed, as they drive altered sleep or their
      interaction with food choice and intake can promote obesity. We discuss data that
      suggest differences in sleep patterns and responses to sleep disruption influence
      sex disparities in weight gain, and that enviromental disturbances alter sleep
      and interact with features of the obesogenic environment that together promote
      obesity.

PMID- 29181710
TI  - The interaction of copper ions with Staphylococcus aureus, Pseudomonas
      aeruginosa, and Escherichia coli: an X-ray absorption near-edge structure (XANES)
      spectroscopy study.
AB  - The antimicrobial properties of copper ions have been known for a long time.
      However, the exact mechanism of action of the transition metal on microorganisms
      has long been unclear. X-ray absorption near-edge structure (XANES) spectroscopy
      at the Cu K edge allows the determination of copper speciation in Staphylococcus
      aureus, Escherichia coli, and Pseudomonas aeruginosa that have been treated with
      Cu(II) and Cu(I) solutions. The death/inactivation of the bacteria was observed
      using plate counting and light microscopy. The Cu K-XANES spectra of the two Gram
      negative bacteria are different than those of the Gram-positive strain. The
      results clearly show that the Cu+-S bond contributes to the antibacterial
      activity of copper, as in the case of silver. The detailed evaluation of the
      differentiated absorption spectra shows that Cu+ (not Cu2+) is the dominant ion
      that binds to the bacteria. Because Cu+ is not the most common copper ion, copper
      is not as effective an antibacterial agent as silver, whose common valency is
      actually + 1. Any reaction of copper with phosphorus from the bacteria can be
      excluded after the evaluation of the absorption spectra.

PMID- 29181711
TI  - A Note from the New Editor in Chief.

PMID- 29181713
TI  - Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?
AB  - Steroid-resistant nephrotic syndrome (SRNS) is a common cause of chronic kidney
      disease in childhood and has a significant risk of rapid progression to end-stage
      renal disease. The identification of over 50 monogenic causes of SRNS has
      revealed dysfunction in podocyte-associated proteins in the pathogenesis of
      proteinuria, highlighting their essential role in glomerular function. Recent
      technological advances in high-throughput sequencing have enabled indication
      driven genetic panel testing for patients with SRNS. The availability of genetic
      testing, combined with the significant phenotypic variability of monogenic SRNS,
      poses unique challenges for clinicians when directing genetic testing. This
      highlights the need for clear clinical guidelines that provide a systematic
      approach for mutational screening in SRNS. The likelihood of identifying a
      causative mutation is inversely related to age at disease onset and is increased
      with a positive family history or the presence of extra-renal manifestations. An
      unequivocal molecular diagnosis could allow for a personalised treatment approach
      with weaning of immunosuppressive therapy, avoidance of renal biopsy and
      provision of accurate, well-informed genetic counselling. Identification of novel
      causative mutations will continue to unravel the pathogenic mechanisms of
      glomerular disease and provide new insights into podocyte biology and glomerular
      function.

PMID- 29181715
TI  - CME INSTRUCTIONS: PET measurements of myocardial blood flow post myocardial
      infarction: Relationship to invasive and cardiac magnetic resonance studies and
      potential clinical applications.

PMID- 29181714
TI  - Discontinuation of Efavirenz in Paediatric Patients: Why do Children Switch?
AB  - BACKGROUND: Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI)
      is used globally as first-line antiretroviral therapy (ART) in combination with a
      dual nucleoside backbone in adults and children from 3 years of age. Up to 40% of
      adults taking efavirenz report central nervous system (CNS) adverse effects, and
      the rates of discontinuation of efavirenz-based treatment are higher than other
      first-line regimens. Data on efavirenz discontinuation are more limited for
      children and adolescents. OBJECTIVE: In this study, we aimed to describe our
      single-centre paediatric experience of efavirenz. METHODS: Retrospective case
      note audit of children and adolescents with perinatally acquired HIV who ever
      received efavirenz. RESULTS: From 1998 and 2014, 51 children and adolescents aged
      <= 18 years received efavirenz-based treatment. Median age at efavirenz
      initiation was 9.4 years (interquartile range [IQR] 7-13). More than half (30/51;
      59%) subsequently switched off efavirenz-15 (29%) following virological failure
      with NNRTI-associated resistance mutations, and 16 (30%) after reporting adverse
      effects. Of those who experienced adverse effects, one-fifth (19.6%) described
      CNS adverse effects, including sleep disturbance, reduced concentration,
      headaches, mood change and psychosis. Four children (three males) developed
      gynaecomastia, two developed hypercholesterolaemia, and one child developed
      Stevens-Johnson syndrome. Comparison between those reporting side effects and the
      rest of the cohort showed no difference in age, sex, initial CD4 cell count,
      viral suppression, length of efavirenz-based treatment, weight, or efavirenz dose
      per kilogram. Median time to switch was 25 months (IQR 10-71) in those who
      experienced side effects and 22 months (IQR 12-50) for virological failure. One
      individual experienced both virological failure and adverse effects. CONCLUSION:
      Almost two-thirds of this paediatric cohort switched from efavirenz-based
      treatment to an alternative regimen, due in equal proportions to both virological
      failure and toxicity. The majority of side effects involved the CNS. First-line
      regimens with improved tolerability and a higher genetic barrier to resistance
      should be the preferred option for children.

PMID- 29181716
TI  - [Imaging characteristics of malignant and benign lesions of skeletal muscle].
AB  - There are many different tumors and tumor-like lesions with variable biological
      behavior that may affect the skeletal musculature. The aim of this study was to
      review the different intramuscular lesions and to provide a classification based
      on their radiological patterns. Intramuscular lesions can present as solid,
      liquid, semiliquid or fat equivalent manifestations and also as diffuse muscle
      enlargement and muscle calcification. Additionally, lesions with mixed patterns
      of the aforementioned alterations can also occur. Benign and malignant muscle
      lesions can often manifest with identical radiological patterns, which is why a
      certain differentiation is often difficult. A systematic radiological description
      and when possible assignment with respect to etiology and dignity depending on
      the patient history is necessary in order to recommend a subsequent histological
      confirmation or to avoid unnecessary confirmation.

PMID- 29181712
TI  - Exosomes and microvesicles in normal physiology, pathophysiology, and renal
      diseases.
AB  - Extracellular vesicles are cell-derived membrane particles ranging from 30 to
      5,000 nm in size, including exosomes, microvesicles, and apoptotic bodies. They
      are released under physiological conditions, but also upon cellular activation,
      senescence, and apoptosis. They play an important role in intercellular
      communication. Their release may also maintain cellular integrity by ridding the
      cell of damaging substances. This review describes the biogenesis, uptake, and
      detection of extracellular vesicles in addition to the impact that they have on
      recipient cells, focusing on mechanisms important in the pathophysiology of
      kidney diseases, such as thrombosis, angiogenesis, tissue regeneration, immune
      modulation, and inflammation. In kidney diseases, extracellular vesicles may be
      utilized as biomarkers, as they are detected in both blood and urine.
      Furthermore, they may contribute to the pathophysiology of renal disease while
      also having beneficial effects associated with tissue repair. Because of their
      role in the promotion of thrombosis, inflammation, and immune-mediated disease,
      they could be the target of drug therapy, whereas their favorable effects could
      be utilized therapeutically in acute and chronic kidney injury.

PMID- 29181717
TI  - Racial disparities in omission of oncotype DX but no racial disparities in
      chemotherapy receipt following completed oncotype DX test results.
AB  - PURPOSE: To examine racial/ethnic disparities in Oncotype DX (ODX) testing among
      patients with node-negative, estrogen receptor (ER)-positive, human epidermal
      growth factor receptor 2 (HER2)-negative breast cancers and possible
      racial/ethnic disparities in chemotherapy receipt following ODX testing within
      Recurrence Score (RS) category (Not Done, Low, Intermediate, High), as well as
      chemotherapy receipt time trends within RS categories. METHODS: A retrospective
      cohort list of 125,288 women who were potentially indicated for ODX testing from
      2010 to 2014 was obtained using the National Cancer Database. We fit multivariate
      logistic regression predicting chemotherapy receipt, adjusting for clinical
      factors, patient demographic factors, and hospital-level factors, separately by
      RS category, and calculated odds ratios (OR) and 95% confidence intervals (CI),
      as well as time trends. RESULTS: Overall, ODX testing was completed for 46.1% of
      Non-Hispanic (NH) Whites, 43.9% of NH Blacks, and 41.7% of Hispanics. Among
      patients who did not receive ODX testing, NH Black and Hispanic women both
      experienced statistically significant increases in chemotherapy receipt relative
      to NH White women (NH Black OR 1.23; 95% CI 1.11-1.37; Hispanic OR 1.23; 95% CI
      1.07-1.42). However, among patients with ODX results, no statistically
      significant racial/ethnic differences in chemotherapy receipt were observed
      within strata of RS category. Trend analyses demonstrated increasing adherence to
      national guidelines for ODX testing. CONCLUSIONS: We identified racial
      disparities in omission of ODX testing but no differences in chemotherapy receipt
      if ODX test results were obtained, suggesting increasing access to ODX testing
      may improve racial equality in efficacious use of adjuvant chemotherapy for ER
      positive HER2-negative breast cancer.

PMID- 29181718
TI  - Willingness of breast cancer patients to undergo biopsy and breast cancer
      clinicians' practices around seeking biopsy at the time of breast cancer relapse.
AB  - PURPOSE: The practice of seeking a biopsy to confirm a metastatic relapse of a
      prior breast cancer is individualized. Tumor samples have well-recognized
      importance in clinical and translational research, but also an increasing role in
      routine care. We sought to determine the attitudes of patients and breast cancer
      clinicians about biopsy at breast cancer relapses. METHODS: Consenting breast
      cancer patients and clinicians completed questionnaires with scenarios of
      decreasing personal benefit and increasing discomfort or inconvenience associated
      with biopsy at relapse of a prior breast cancer. For each scenario, patients were
      asked whether they would, would not, or were unsure about agreeing to a biopsy.
      Clinicians provided information about their practice, research activities, and
      usual biopsy habits. They were asked to estimate how often patients would agree
      to a biopsy under each of the conditions presented to patient participants.
      RESULTS: The majority of patients expressed a willingness to undergo a biopsy
      procedure of modest inconvenience and discomfort to establish an uncertain
      diagnosis, guide treatment, to participate in a trial, or for research purposes
      only. About 50% of patients indicated that they would undergo an invasive biopsy
      procedure requiring IV sedation or general anesthetic for purely altruistic
      reasons. In spite of being a largely academic group, clinician respondents
      underestimated patient willingness to have a biopsy in all scenarios,
      particularly when there was no attached personal benefit. CONCLUSION: Breast
      cancer patients were very willing to undergo biopsy at breast cancer relapse for
      their routine care, clinical trials, or for research only. Clinicians act as the
      intermediary between patients and tumor tissue repositories, and clinician
      perceptions and practices should shift to match the altruistic attitudes of
      breast cancer patients.

PMID- 29181719
TI  - Environmental biotechnology and engineering: crucial tools for improving and
      caring for the environment and the quality of life of modern societies.

PMID- 29181720
TI  - Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression
      of Astrocytes in Collagen Gels.
AB  - Glaucoma is a common optic neuropathy characterized by retinal ganglion cell
      death. Elevated intraocular pressure (IOP), a key risk factor for glaucoma, leads
      to significant biomechanical deformation of optic nerve head (ONH) cells and
      tissues. ONH astrocytes respond to this deformation by transforming to a
      reactive, proliferative phenotype, which has been implicated in the progression
      of glaucomatous vision loss. However, little is known about the mechanisms of
      this transformation. In this study, we developed a 3D collagen gel culture system
      to mimic features of ONH deformation due to elevated IOP. Compressive loading of
      astrocyte-seeded collagen gels led to cell alignment perpendicular to the
      direction of strain, and increased astrocyte activation, as assayed by GFAP,
      vimentin, and s100beta levels, as well as MMP activity. This proof-of-concept
      study shows that this system has potential for studying mechanisms of astrocyte
      mechanobiology as related to the pathogenesis of glaucoma. Further work is needed
      to establish the possible interplay of mechanical stimulation, matrix properties,
      and hypoxia on the observed response of astrocytes.

PMID- 29181721
TI  - On the Failure Initiation in the Proximal Human Femur Under Simulated Sideways
      Fall.
AB  - The limitations of areal bone mineral density measurements for identifying at
      risk individuals have led to the development of alternative screening methods for
      hip fracture risk including the use of geometrical measurements from the proximal
      femur and subject specific finite element analysis (FEA) for predicting femoral
      strength, based on quantitative CT data (qCT). However, these methods need more
      development to gain widespread clinical applications. This study had three aims:
      To investigate whether proximal femur geometrical parameters correlate with
      obtained femur peak force during the impact testing; to examine whether or not
      failure of the proximal femur initiates in the cancellous (trabecular) bone; and
      finally, to examine whether or not surface fracture initiates in the places where
      holes perforate the cortex of the proximal femur. We found that cortical
      thickness around the trochanteric-fossa is significantly correlated to the peak
      force obtained from simulated sideways falling (R 2 = 0.69) more so than femoral
      neck cortical thickness (R 2 = 0.15). Dynamic macro level FE simulations
      predicted that fracture generally initiates in the cancellous bone compartments.
      Moreover, our micro level FEA results indicated that surface holes may be
      involved in primary failure events.

PMID- 29181722
TI  - Evaluation of Decoding Algorithms for Estimating Bladder Pressure from Dorsal
      Root Ganglia Neural Recordings.
AB  - A closed-loop device for bladder control may offer greater clinical benefit
      compared to current open-loop stimulation devices. Previous studies have
      demonstrated the feasibility of using single-unit recordings from sacral-level
      dorsal root ganglia (DRG) for decoding bladder pressure. Automatic online
      sorting, to differentiate single units, can be computationally heavy and
      unreliable, in contrast to simple multi-unit thresholded activity. In this study,
      the feasibility of using DRG multi-unit recordings to decode bladder pressure was
      examined. A broad range of feature selection methods and three algorithms
      (multivariate linear regression, basic Kalman filter, and a nonlinear
      autoregressive moving average model) were used to create training models and
      provide validation fits to bladder pressure for data collected in seven
      anesthetized feline experiments. A non-linear autoregressive moving average
      (NARMA) model with regularization provided the most accurate bladder pressure
      estimate, based on normalized root-mean-squared error, NRMSE, (17 +/- 7%). A
      basic Kalman filter yielded the highest similarity to the bladder pressure with
      an average correlation coefficient, CC, of 0.81 +/- 0.13. The best algorithm set
      (based on NRMSE) was further evaluated on data obtained from a chronic feline
      experiment. Testing results yielded a NRMSE and CC of 10.7% and 0.61,
      respectively from a model that was trained on data recorded 2 weeks prior. From
      offline analysis, implementation of NARMA in a closed-loop scheme for detecting
      bladder contractions would provide a robust control signal. Ultimate integration
      of closed-loop algorithms in bladder neuroprostheses will require evaluations of
      parameter and signal stability over time.

PMID- 29181723
TI  - Electrical Conductivity Method to Determine Sexual Dimorphisms in Human
      Temporomandibular Disc Fixed Charge Density.
AB  - To investigate potential mechanisms associated with the increased prevalence of
      temporomandibular joint (TMJ) disorders among women, the study objective was to
      determine sex-dependent and region-dependent differences in fixed charge density
      (FCD) using an electrical conductivity method. Seventeen TMJ discs were harvested
      from nine males (77 +/- 4 years) and eight females (86 +/- 4 years). Specimens
      were prepared from the anterior band, posterior band, intermediate zone, medial
      disc and lateral disc. FCD was determined using an electrical conductivity
      method, assessing differences among disc regions and between sexes. Statistical
      modeling showed significant effects for donor sex (p = 0.002), with cross-region
      FCD for male discs 0.051 +/- 0.018 milliequivalent moles per gram (mEq/g) wet
      tissue and 0.043 +/- 0.020 mEq/g wet tissue for female discs. FCD was
      significantly higher for male discs compared to female discs in the posterior
      band, with FCD 0.063 +/- 0.015 mEq/g wet tissue for male discs and 0.032 +/-
      0.020 mEq/g wet tissue for female discs (p = 0.050). These results indicate FCD
      contributes approximately 20% towards TMJ disc compressive modulus, through
      osmotic swelling pressure regulation. Additionally, FCD regulates critical
      extracellular ionic/osmotic and nutrient environments. Sexual dimorphisms in TMJ
      disc FCD, and resulting differences in extracellular ionic/osmotic and nutrient
      environments, could result in altered mechano-electro-chemical environments
      between males and females and requires further study.

PMID- 29181724
TI  - Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or
      without antiretroviral therapy.
AB  - Persistence of HIV-1 reservoirs in the central nervous system (CNS) is an
      obstacle to cure strategies. However, little is known about residual viral
      distribution, viral replication levels, and genetic diversity in different brain
      regions of HIV-infected individuals on combination antiretroviral therapy (cART).
      Because myeloid cells particularly microglia are likely major reservoirs in the
      brain, and more microglia exist in white matter than gray matter in a human
      brain, we hypothesized the major viral reservoirs in the brain are the white
      matter reflected by higher levels of viral DNA. To address the issue, we used the
      Chinese rhesus macaque (ChRM) model of SIV infection, and treated 11 SIVmac251
      infected animals including long-term nonprogressors with cART for up to 24 weeks.
      SIV reservoirs were assessed by SIV DNA levels in 16 specific regions of the
      brain and 4 regions of spinal cord. We found relatively high frequencies of SIV
      in basal ganglia and brain stem compared to other regions. cART-receiving animals
      had significantly lower SIV DNA levels in the gray matter than white matter.
      Moreover, a shortened envelope gp120 with 21 nucleotide deletions and guanine-to
      adenine hypermutations were observed. These results demonstrate that SIV enters
      the CNS in SIV-infected ChRM with a major reservoir in the white matter after
      cART; the SIV/ChRM/cART is an appropriate model for studying HIV CNS reservoirs
      and testing new eradication strategies. Further, examining multiple regions of
      the CNS may be needed when assessing whether an agent is successful in reducing
      the size of SIV reservoirs in the CNS.

PMID- 29181725
TI  - Association between left atrial phasic conduit function and early atrial
      fibrillation recurrence in patients undergoing electrical cardioversion.
AB  - BACKGROUND: Diastolic dysfunction promotes atrial fibrillation (AF) inducing left
      atrial (LA) remodeling, with chamber dilation and fibrosis. Predominance of LA
      phasic conduit (LAC) function should reflect not only chamber alterations but
      also underlying left ventricular (LV) filling impairment. Thus, LAC was tested as
      possible predictor of early AF relapse after electrical cardioversion (EC).
      METHODS: 96 consecutive patients, who underwent EC for persistent non-valvular
      AF, were prospectively enrolled. Immediately after successful EC (3 h +/- 15
      min), an echocardiographic apical four-chamber view was acquired with transmitral
      velocities, annular tissue Doppler and simultaneous LV and LA three-dimensional
      full-volume datasets. Then, from LA-LV volumetric curves we computed LAC as: [(LV
      maximum - LV minimum) - (LA maximum - LA minimum) volume], expressed as % LV
      stroke volume. LA pump, immediately post-EC, was assumed and verified as being
      negligible. Sinus rhythm persistence at 1 month was checked with ECG-Holter
      monitoring. RESULTS: At 1 month 62 patients were in sinus rhythm and 34 in AF. AF
      patients presented pre-EC higher E/e values (p = 0.012), no major LA volume
      differences (p = NS), but a stiffer LV cavity (p = 0.012) for a comparable LV
      capacitance (p = 0.461). Conduit contributed more (p < 0.001) to LV stroke volume
      in AF subpopulation. Multiple regression revealed LAC as the most significant AF
      predictor (p = 0.013), even after correction for biometric characteristics and
      pharmacotherapy (p = 0.008). CONCLUSION: Our data suggest that LAC larger
      contribution to LV filling soon after EC reflects LA-LV stiffening, which skews
      atrioventricular interaction leading to AF perpetuation and makes conduit
      dominance a powerful predictor of early AF recurrence.

PMID- 29181726
TI  - The inhibition of polyamine biosynthesis weakens the drought tolerance in white
      clover (Trifolium repens) associated with the alteration of extensive proteins.
AB  - Changes of endogenous polyamine (PA) levels could be a key adaptive response to
      drought in plants. White clover pretreated with or without dicyclohexylamine
      (DCHA), an inhibitor of PA biosynthesis, was subjected to drought stress induced
      by 18% polyethylene glycol 6000 for 8 days in controlled growth chambers. Results
      showed that drought stress significantly increased endogenous PA content, whereas
      DCHA significantly decreased PA accumulation under drought stress. The attenuate
      PA biosynthesis was unfavorable for plant growth and drought tolerance, as
      reflected by significantly lower relative water content, relative growth rate,
      instantaneous water use efficiency, and cell membrane stability in leaves in
      response to drought. On the basis of proteomic analysis, the inhibition of PA
      synthesis decreased the accumulation of many key differentially expressed
      proteins including (1) ribosomal structure and biogenesis: elongation factor,
      ribosomal protein S10E, and 30S ribosomal protein; (2) amino acid transport and
      metabolism: cysteine synthase, delta-1-pyrroline-5-carboxylate synthetase, and
      glutamate decarboxylase; (3) carbohydrate metabolism and energy production:
      photosystem apoprotein, sucrose-phosphate synthase, phosphogluconate
      dehydrogenase, sucrose-phosphatase, NADH oxidoreductase, and ATP synthase; (4)
      antioxidant metabolism: catalase, peroxidase I, ascorbate peroxidase, and
      glutathione S-transferase; and (5) other biological processes: heat shock protein
      70, heat shock protein 90, and calcium-dependent protein kinase associated with
      the decreased drought tolerance in white clover. These findings indicate that PAs
      play a critical role in the regulation of growth, ribosome, amino acid and energy
      metabolism, and antioxidant reactions in white clover under drought stress.
      Drought-induced increases in endogenous PAs could be one of key adaptive
      responses against drought stress in white clover.

PMID- 29181727
TI  - Hospital-acquired infection in patients with systemic lupus erythematosus: a case
      control study in a southern Chinese population.
AB  - The objective of this study is to investigate the current situation of hospital
      acquired infection (HAI) in lupus patients from a southern Chinese population. A
      case-control study was performed. Data from Jan. 2007 to Jan. 2017 were
      collected. Each lupus patient with HAI was compared with two control individuals
      without infection selected from the same period of time. Three hundred and sixty
      episodes of HAI were analyzed. The average Systemic Lupus Erythematosus Disease
      Activity Index (SLEDAI) score at admission was 13.2 +/- 7.2. The respiratory
      tract (58.8%) was most commonly involved, followed by the bloodstream (10.9%).
      Most episodes were bacteria-associated (50.0%), followed by viral infection
      (34.8%) and fungal infection (15.2%). Pathogenic bacteria were isolated in 87
      episodes, among which 60 episodes were gram-negative bacteria (GNB)-related.
      Multidrug-resistant strains were detected in 46.4% of bacterial isolates. Fungi
      were isolated in 49 episodes. Candida albicans (46.9%) was the leading pathogen.
      Fifty-four episodes of virus infection were confirmed. In multivariate analysis,
      SLEDAI score (OR 1.1, 95% CI 1.1-1.2, P < 0.001), lupus nephritis (OR 3.7, 95% CI
      2.7-5.1, P < 0.001), high dose of GC (OR 2.7, 95% CI 1.8-3.9, P < 0.001), and
      treatment with CYC (OR 2.9, 95% CI 2.1-4.0, P < 0.001) were risk factors for HAI.
      HAI in Chinese lupus patients had a unique epidemiology feature, which was
      characterized by common respiratory tract and bloodstream involvement and
      predominance of GNB with a high drug resistance rate. A variety of new pathogens
      including fungi and viruses emerged in the HAI patients. A history of nephritis
      or a higher SLEDAI score in SLE patients predicted HAI. Moreover, treatment with
      high dose of GC and CYC was also the main risk factor for HAI.

PMID- 29181728
TI  - Comparison of composite indices with global synovitis score on ultrasound for
      detecting remission.
AB  - We aimed to compare composite indices with Ultrasound Global Synovitis Score
      (GLOESS) for remission in rheumatoid arthritis (RA). RA patients in remission
      according to the clinician were investigated with Disease Activity Score28
      (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity
      Index (SDAI), and RAPID-3 (Routine Assessment of Patient Index Data 3).
      Ultrasonography was performed using the GLOESS scores. Patients in CDAI-remission
      had lower GLOESS (median (IQR), 5(3-9.75) vs 7(4-11.75), p = 0.048) with a
      similar trend in SDAI (5(3-9.25) vs 7(4-11.25), p = 0.064). This was not observed
      with DAS28-CRP and RAPID3. Our results show that CDAI is superior to other
      indices to assess remission in RA.

PMID- 29181729
TI  - Methyl group assignment using pseudocontact shifts with PARAssign.
AB  - A new version of the program PARAssign has been evaluated for assignment of NMR
      resonances of the 76 methyl groups in leucines, isoleucines and valines in a 25
      kDa protein, using only the structure of the protein and pseudocontact shifts
      (PCS) generated with a lanthanoid tag at up to three attachment sites. The number
      of reliable assignments depends strongly on two factors. The principle axes of
      the magnetic susceptibility tensors of the paramagnetic centers should not be
      parallel so as to avoid correlated PCS. Second, the fraction of resonances in the
      spectrum of a paramagnetic sample that can be paired with the diamagnetic
      counterparts is critical for the assignment. With the data from two tag positions
      a reliable assignment could be obtained for 60% of the methyl groups and for many
      of the remaining resonances the number of possible assignments is limited to two
      or three. With a single tag, reliable assignments can be obtained for methyl
      groups with large PCS near the tag. It is concluded that assignment of methyl
      group resonances by paramagnetic tagging can be particularly useful in
      combination with some additional data, such as from mutagenesis or NOE-based
      experiments. Approaches to yield the best assignment results with PCS generating
      tags are discussed.

PMID- 29181730
TI  - Preservation and Storage Stability of Extracellular Vesicles for Therapeutic
      Applications.
AB  - Recently, extracellular vesicles (EVs)-including exosomes, microvesicles, and
      others-have attracted interest as cell-derived biotherapeutics and drug delivery
      vehicles for a variety of applications. This interest stems from favorable
      properties of EVs, including their status as mediators of cell-cell communication
      via transfer of biological cargo and their reported ability to cross biological
      barriers that impede many delivery systems. However, there are many challenges to
      translation and widespread application of EV-based therapeutics. One such
      challenge that has yet to be extensively studied involves EV preservation and
      storage, which must be addressed to enable use of therapeutic EVs beyond resource
      intensive settings. Studies to date suggest that the most promising mode of
      storage is - 80 degrees C; however, understanding of storage-mediated effects is
      still limited. Additionally, the effects of storage appear to vary with sample
      source. The lack of knowledge about and standardization of EV storage may
      ultimately hinder widespread clinical translation. This mini-review reports
      current knowledge in the field of EV preservation and storage stability and
      highlights future directions in the area that could be critical to eventual
      development of EV therapies.

PMID- 29181731
TI  - Sodium Tanshinone II A Sulfonate Injection as Adjuvant Treatment for Unstable
      Angina Pectoris: A Meta-Analysis of 17 Randomized Controlled Trials.
AB  - OBJECTIVE: To systematically evaluate the effectiveness and safety of Sodium
      Tanshinone II A Sulfonate Injection (STS) as one adjuvant therapy for treating
      unstable angina pectoris (UAP). METHODS: Randomized controlled trials (RCTs) of
      UAP treated by STS were searched in the China National Knowledge Infrastructure
      Database (CNKI), VIP Database for Chinese Technical Periodicals (VIP), Wanfang
      Database, the Chinese Biomedical Literature Database (CBM), Web of Science, the
      Cochrane Library, Embase, and PubMed, which from inception to January, 2016. The
      Cochrane Risk Assessment Tool was used to evaluate the methodological quality of
      the RCTs. The Review Manager 5.3 software was used to conduct the metaanalysis.
      RESULTS: The results showed that 17 RCTs involving 1,372 patients were included.
      The meta-analysis indicated that the combined use of STS and Western medicine
      (WM) in the treatment of UAP can obviously improve the total effective rate [risk
      ratio (RR)=1.31, 95% confidence interval (CI) (1.24,1.39), P<0.0001], and the
      total effective rate of electrocardiogram [RR=1.43, 95% CI (1.30,1.56),
      P<0.0001], decrease the level of CRP [mean difference (MD)=-3.06, 95%CI (-3.85,
      2.27), P<0.00001], fibrinogen [MD=-1.03, 95% CI (-1.16,-0.89), P<0.00001], and
      whole blood high shear viscosity [MD=-0.70, 95% CI (-0.92,-0.49), P<0.00001].
      Additionally, the occurrence of adverse drug reaction of the experimental group
      was significantly higher than that of the control group [RR=3.57, 95% CI (1.28,
      9.94), P<0.05]. CONCLUSIONS: Compared with WM, the combined use of STS was more
      effective.

PMID- 29181732
TI  - Reporting characteristics of case reports of acupuncture therapy with CARE
      guidelines.
AB  - OBJECTIVE: To investigate the reporting characteristics of case reports of
      acupuncture therapy with CAse Report (CARE) guidelines, and to explore the
      applicability of the guidelines for these case reports. METHODS: Case reports
      published from January 1, 2011 to December 31, 2013, were identified by searching
      PubMed and the China Biomedicine Database by using MeSH terms. Screening and data
      extraction of case reports were conducted by two independent researchers.
      Assessments based on CARE guidelines and data analysis were conducted by using
      Excel 2003 and RevMan 5.0. RESULTS: A total of 61 case reports published in 19
      journals were identified, which involved 16 major types of diseases. Fifteen
      (24.6%) case reports declared no conflict of interests, and 5 (8.2%) reported
      funding sources. None of these case reports met all items of CARE guidelines, and
      only 6 subordinate items were fully reported among 50% of the case reports.
      Subgroup analysis indicated that case reports published in English or those that
      did not have competing interests had higher reporting quality. CONCLUSIONS: The
      reporting quality of case reports of acupuncture therapy is rather low. The
      reason might be a lack of awareness among authors and the poor dissemination of
      information regarding CARE guidelines in China. More evaluation studies are
      needed to promote and improve adherence to CARE guidelines. Moreover, an extended
      version of CARE guidelines should be developed for cases reports of special
      interventions such as acupuncture or adverse events caused by interventions.

PMID- 29181733
TI  - Modified Xiaochaihu decoction () promotes collagen degradation and inhibits
      pancreatic fibrosis in chronic pancreatitis rats.
AB  - OBJECTIVE: To investigate the effect of Modified Xiaochaihu Decoction (MXD, ) on
      collagen degradation in rats with chronic pancreatitis (CP). METHODS: Rats were
      injected dibutyltin dichloride (DBTC, 7 mg/kg of body weight) into the right
      caudal vein to induce CP model. Thirty heallhy male Wistar rats were randomly
      divided into three groups by a random number table: the control, the model and
      the treatment groups. Rats of treatment group were administered MXD (10 g/kg of
      body weight) orally once daily starting from the day post-model establishment.
      Pancreatic tissues were harvested after 28-day feeding and fibrosis was evaluated
      by picro-sirius red staining. The contents of collagen type I and III were
      detected using enzymelinked immunosorbent assay (ELISA), the expression of matrix
      metalloproteinase 13 (MMP13) and tissue inhibitor of metalloproteinase 1 (TIMP1)
      was analyzed by Western blot and real-time polymerase chain reaction (PCR).
      RESULTS: The fifi brosis scoring of pancreatic tissues, the concentrations of
      collagen type I and III, the expression levels of MMP13 and TIMP1 proteins and
      mRNA in the model group were all increased compared with the control group
      (P<0.05). After treatment with MXD, the fifi brosis scoring of pancreatic
      tissues, the concentrations of collagen type I and III, the expression levels of
      MMP13 proteins and mRNA in the teatment group were all decreased compared with
      the model group (P<0.05), but there were no signififi cant differences in the
      expression levels of TIMP1 proteins and mRNA (P>0.05). CONCLUSIONS: MXD could
      promote collagen degradation and reverse pancreatic fifi brosis in CP rats via a
      mechanism involve up-regulation of MMP13 expression.

PMID- 29181734
TI  - Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits
      determined using empirically derived kinships from the Busselton Health Study.
AB  - Over two billion adults are overweight or obese and therefore at an increased
      risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits
      genetically correlated with CMS may provide insight into CMS aetiology. The aim
      of this study was to utilise an empirically derived genetic relatedness matrix to
      calculate heritabilities and genetic correlations between CMS and anthropometric
      traits to determine whether they share genetic risk factors (pleiotropy). We used
      genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health
      Study participants. Exploiting both known and unknown relatedness, empirical
      kinship probabilities were estimated using these SNP data. General linear mixed
      models implemented in SOLAR were used to estimate narrow-sense heritabilities (h
      2) and genetic correlations (r g) between 15 anthropometric and 9 CMS traits.
      Anthropometric traits were adjusted by body mass index (BMI) to determine whether
      the observed genetic correlation was independent of obesity. After adjustment for
      multiple testing, all CMS and anthropometric traits were significantly heritable
      (h 2 range 0.18-0.57). We identified 50 significant genetic correlations (r g
      range: - 0.37 to 0.75) between CMS and anthropometric traits. Five genetic
      correlations remained significant after adjustment for BMI [high density
      lipoprotein cholesterol (HDL-C) and waist-hip ratio; triglycerides and waist-hip
      ratio; triglycerides and waist-height ratio; non-HDL-C and waist-height ratio;
      insulin and iliac skinfold thickness]. This study provides evidence for the
      presence of potentially pleiotropic genes that affect both anthropometric and CMS
      traits, independently of obesity.

PMID- 29181735
TI  - [Oral anticoagulation and platelet inhibition after atrial appendage occlusion].
AB  - In Europe left atrial appendage occluders (LAAO) are most frequently used in
      patients with contraindications for oral anticoagulation (OAC); therefore, the
      classical therapeutic OAC scheme from the PROTECT-AF trial (vitamin K antagonist
      plus acetylsalicylic acid) is usually changed to dual anti-platelet therapy
      (DAPT) after implantation of a Watchman(r) or Amulet(r) LAAO (St. Jude
      Medical/Abbott, Eschborn, Germany). For many years, patients with an LAAO
      received DAPT for 1-6 months. The current standard comprises DAPT for 3 months,
      followed by permanent acetylsalicylic acid monotherapy if the transesophageal
      echocardiogram excludes a thrombus at the site of the LAAO. In patients with high
      risk of bleeding, anti-platelet therapy can be stopped at 3 months after an
      individual risk-benefit calculation. There are no randomized studies on the risk
      of bleeding and stroke/embolism in patients with an LAA occluder under DAPT
      versus OAC. Experience from the EWOLUTION registry shows that NOACs may be used
      as an alternative with low bleeding and thrombus risks. In patients with a
      suboptimal implantation result, thrombus on the LAAO or specific risk factors,
      variations of the standard scheme have to be applied and if necessary lifelong
      DAPT or NOAC therapy has to be used. Thrombi on the LAAO occur in approximately 4
      6% of patients and are associated with a very low short-term stroke risk.

PMID- 29181736
TI  - Adoptive Induced Antigen-Specific Treg Cells Reverse Inflammation in Collagen
      Induced Arthritis Mouse Model.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease that may cause bone
      damage and worsening disability. Manipulating antigen-specific Treg cells is a
      promising approach to treat autoimmune disease since the immune suppressive
      function of Treg cells has the feature of antigen specificity which could avoid
      overall immune suppression. It has been known that the function of Treg cells is
      impaired in RA, and adoptive transfer of Treg cells is effective in suppressing
      RA. Here, we designed a new approach to generate antigen-specific Treg cells by
      culturing CD4+ T cells from mice with RA onset, and we also proved that the
      adoptive transfer of these antigen-specific Treg cells reversed the collagen
      induced arthritis (CIA) progression by suppressing the key inflammatory cytokine
      TNF-alpha. Further analysis showed that the transferred Treg cells were stable in
      vivo. These findings suggest this novel approach may have clinical applications
      for treatment of autoimmunity, including RA and other autoimmune disorders.

PMID- 29181737
TI  - MiR-548a-3p Promotes Keratinocyte Proliferation Targeting PPP3R1 after Being
      Induced by IL-22.
AB  - Psoriasis is an immune-mediated chronic skin disorder where T cells play a main
      role, and numerous inflammatory cytokines are implicated in its pathogenesis by
      initiating keratinocyte proliferation. Interleukin-22 (IL-22), an IL-10 family
      cytokines, is critical in the pathogenesis and development of psoriasis. To
      determine the target of microRNA (miR) -548a-3p and investigate its role in
      keratinocyte proliferation after treating human keratinocytes (HaCaT) with IL-22,
      we used quantitative reverse transcriptase PCR to measure the expression of miR
      548a-3p in both HaCaT cells stimulated with IL-22 and psoriatic lesions, and then
      detected the biological function of miR-548a-3p in HaCaT cells by performing
      Counting Kit-8 (CCK-8) assays. Luciferase reporter assay was conducted to
      determine the target gene of miR-548a-3p. Immunohistochemistry and Western blot
      were performed to verify the target gene. Results showed that miR-548a-3p was
      significantly upregulated both in HaCaT cells treated with IL-22 and psoriatic
      lesions. The over expression of miR-548a-3p could promote the proliferation of
      HaCaT cells. Luciferase was mutated in the 3'UTR of PPP3R1, a gene coding
      Calcineurin. Immunohistochemistry and Western blot demonstrated that the
      expression of PPP3R1 decreased respectively in psoriatic lesions and HaCaT cells.
      In conclusion, the expression of miR-548a-3p is upregulated in IL-22 mediated
      keratinocyte proliferative disorder like psoriasis. The impact of miR-548a-3p on
      keratinocyte proliferation may be implemented by targeting PPP3R1 and T
      regulatory cells may be involved in the pathogenesis of psoriasis.

PMID- 29181738
TI  - Long-term survival after multidisciplinary therapy for brain metastases from
      asymptomatic esophageal adenocarcinoma.
AB  - Asymptomatic T1 (invaded submucosa) esophageal carcinoma rarely metastasizes to
      the brain. A 53-year-old Japanese man complaining of right hemiparesis and
      convulsion was admitted to our hospital. Brain imaging demonstrated a ring-like,
      enhanced brain tumor in the left parietal lobe. The pathological findings of the
      resected tumor were consistent with a metastatic adenocarcinoma from the
      gastrointestinal tract. Additional examinations revealed an elevated-type tumor
      in the lower third of the thoracic esophagus. The patient underwent thoracoscopic
      esophagectomy with lymph node dissection followed by reconstruction with gastric
      tube substitution. The immunohistochemical findings of the resected specimen were
      similar to those of the metastatic brain tumor. Although the patient received
      adjuvant chemotherapy (5-fluorouracil, docetaxel plus cisplatin), a solitary
      small brain metastasis was detected 4 months after esophagectomy. Excision of the
      sequential metastases with whole-brain radiation therapy and gamma-knife therapy
      were performed. The patient survived for 50 months after beginning the initial
      treatment. This report describes a rare case of brain metastases from T1
      esophageal adenocarcinoma in a patient without gastrointestinal symptoms.

PMID- 29181739
TI  - Stochasticity in cultural evolution: a revolution yet to happen.
AB  - Over the last 40 years or so, there has been an explosion of cultural evolution
      research in anthropology and archaeology. In each discipline, cultural
      evolutionists investigate how interactions between individuals translate into
      group level patterns, with the aim of explaining the diachronic dynamics and
      diversity of cultural traits. However, while much attention has been given to
      deterministic processes (e.g. cultural transmission biases), we contend that
      current evolutionary accounts of cultural change are limited because they do not
      adopt a systematic stochastic approach (i.e. accounting for the role of chance).
      First, we show that, in contrast with the intense debates in ecology and
      population genetics, the importance of stochasticity in evolutionary processes
      has generated little discussion in the sciences of cultural evolution to date.
      Second, we speculate on the reasons, both ideological and methodological, why
      that should be so. Third, we highlight the inadequacy of genetically-inspired
      stochastic models in the context of cultural evolution modelling, and ask which
      fundamental stochastic processes might be more relevant to take up. We conclude
      that the field of cultural evolution would benefit from a stochastic revolution.
      For that to occur, stochastic models ought to be developed specifically for
      cultural data and not through a copy-pasting of neutral models from population
      genetics or ecology.

PMID- 29181740
TI  - Impact of mitral valve intervention with left ventricular assist device
      implantation on postoperative outcomes and morphologic change.
AB  - Although mitral regurgitation (MR) is prevalent in patients with end-stage heart
      failure, the impact of mitral valve (MV) surgery on outcomes after left
      ventricular assist device (LVAD) implantation and morphologic changes of MV
      remains unclear. We retrospectively reviewed 74 patients who underwent LVAD
      implantation as a bridge to transplant. Of these, 11 (15%) underwent MV repair
      concomitant with or prior to LVAD implantation, while 27 patients with
      preoperative significant (moderate or greater) MR did not undergo concomitant MV
      surgery. The mean interval between LVAD implantation and the last
      echocardiographic examination was 913 days. Irrespective of MV surgery,
      significant LV reverse remodeling including decreased LV and left atrial
      dimension and improved MR severity was observed in all patients except for
      patients with prior MV surgery. Histopathological examination of explanted hearts
      removed at heart transplantation (n = 69) or autopsy (n = 5) revealed that the MV
      annulus was still dilated (mean perimeter 11.7 cm) in the patients with
      preoperative significant MR and no concomitant MV surgery. Concomitant MV surgery
      at the time of LVAD implantation for significant MR might not be always necessary
      for bridge to transplant or destination therapy cases. However, it might be
      required in patients having potential for cardiac recovery or patients with
      severe pulmonary hypertension and depressed right ventricle.

PMID- 29181741
TI  - Longitudinal Associations between Oppositional Defiant Symptoms and Interpersonal
      Relationships among Chinese Children.
AB  - Children with oppositional defiant disorder (ODD) are at increased risk for
      developing poor relationships with people around them, but the longitudinal links
      between ODD symptoms and subsequent interpersonal functioning remain unclear. In
      the current study, we examined the bidirectional associations between ODD
      symptoms and children's relationships with parents, peers, and teachers. We
      included separate analyses for parent vs. teacher reports of ODD symptoms, with
      regard to subsequent interpersonal relationships. Participants included 256
      children with ODD, recruited in China, along with their parents and teachers,
      assessed at three time points roughly two years apart. Parents and teachers
      reported child ODD symptoms at each time point, and children reported their
      perceptions of father- and mother-child attachment, peer relationships, and
      teacher-student relationships across the three time points. ODD symptoms reported
      either by parents or teachers predicted impairments in interpersonal functioning.
      Meanwhile, child interpersonal impairments with peers and teachers predicted
      subsequent increase in teacher-reported ODD symptoms. These findings highlight
      the importance of transactional models of influence-and of considering early
      intervention for ODD in protecting children from developing further deficits and
      impairments. Additionally, we discuss the perspectives of multiple informants on
      ODD symptoms, including their different patterns of association with subsequent
      interpersonal relationships.

PMID- 29181742
TI  - Correction to: Early Colorectal Cancer Detected by Machine Learning Model Using
      Gender, Age, and Complete Blood Count Data.
AB  - The article Early Colorectal Cancer Detected by Machine Learning Model Using
      Gender, Age, and Complete Blood Count Data, written by Mark C. Hornbrook, Ran
      Goshen, Eran Choman, Maureen O'Keeffe-Rosetti, Yaron Kinar, Elizabeth G. Liles,
      and Kristal C. Rust, was originally published Online First without open access.

PMID- 29181744
TI  - The versatile mutational "repertoire" of Escherichia coli GroEL, a multidomain
      chaperonin nanomachine.
AB  - The bacterial chaperonins are highly sophisticated molecular nanomachines,
      controlled by the hydrolysis of ATP to dynamically trap and remove from the
      environment unstable protein molecules that are susceptible to denaturation and
      aggregation. Chaperonins also act to assist in the refolding of these unstable
      proteins, providing a means by which these proteins may return in active form to
      the complex environment of the cell. The Escherichia coli GroE chaperonin system
      is one of the largest protein supramolecular complexes known, whose quaternary
      structure is required for segregating aggregation-prone proteins. Over the course
      of more than two decades of research on GroE, it has become accepted that GroE,
      more specifically the GroEL subunit, is a "high-tolerance" molecular system,
      capable of accommodating numerous mutations, while retaining its molecular
      integrity. In some cases, a given site of mutation was revealed to be absolutely
      required for GroEL function, providing hints regarding the network of signals and
      triggers that propel this unique system. In other instances, however, a mutation
      has produced a more delicate response, altering only part of, or in some cases,
      only a single facet of, the molecular mechanism, and these mutants have often
      provided invaluable hints on the extent of the complexity underlying chaperonin
      assisted protein folding. In this review, we highlight some examples of the
      latter type of GroEL mutants which compose the unique "mutational repertoire" of
      GroEL and touch upon the important clues that each mutant provided to the overall
      effort to elucidate the details of GroE action.

PMID- 29181745
TI  - Salicylate Intoxication in an Infant: A Case Report.
AB  - In children, the most common cause of an elevated anion gap (AG) with ketonemia,
      ketonuria, hyperglycemia, and glycosuria is diabetic ketoacidosis. However, when
      the clinical history is not clear, other causes must be considered. A 9-month-old
      girl was transferred to our pediatric intensive care unit (PICU) because of
      severe metabolic acidosis. On admission, she presented with Kussmaul breathing,
      tachycardia, irritability, and fever. Blood gasses revealed metabolic acidosis
      with superimposed respiratory alkalosis and elevated AG. Fluid replacement and
      bicarbonate for urine alkalinization were started. Ketonemia, acidic urine with
      glycosuria, ketonuria, and high blood glucose prompted an insulin infusion.
      Measurement of plasma salicylate confirmed toxic levels. When confronted, the
      parents admitted to accidentally preparing the child's bottle with water
      containing salicylic acid 1000 mg. Although the incidence of salicylate
      intoxication has declined, it remains an important cause of pediatric morbidity
      and mortality.

PMID- 29181746
TI  - Severe Dehiscence of Gastrojejunal Anastomosis after Gastric Bypass: Its Cure by
      Using Partially Covered Stent and Avoiding Migration.
AB  - BACKGROUND: Gastric leak is a severe complication of gastric bypass that is
      associated with significant morbidity and mortality. Anastomosis dehiscence
      usually occurs at gastrojejunal anastomosis and can appear simultaneously with
      gastric leak, for which treatment can be a challenge. Fistula may have several
      clinical impacts, depending on patient-related factors, fistula characteristics,
      onset time, and therapy proposal. Abdominal toilet, drainage, gastrostomy, and
      revisional surgery constitute the traditional approaches to dehiscence and
      fistula closure, with variable results. Currently, endoscopic stents are gaining
      space, promoting fistula sealing, secretion deviation, treating gastric
      stricture, and allowing early oral diet. Herein, we present a case of severe
      gastrojejunal anastomosis dehiscence treated with partially covered stent.
      MATERIALS AND METHODS: We present a video of a 39-year-old man with a body mass
      index of 40 Kg/m2 who underwent a Roux-en-Y gastric bypass and presented fever
      and leukocytosis. Gastric leak was diagnosed 7 days after the bariatric surgery.
      At first, he was submitted to three reoperations: laparotomy with abdominal
      toilet, abdominal drain, and gastrostomy. Sepsis was controlled, but drain output
      maintained the same debit. On the 22nd POD, it was decided to place a metallic
      stent. As the first step, an endoscopist looked at the lesser curvature. There
      was no continuity to the alimentary limb, and the anastomosis was disrupted.
      Careful inflation and washing was done, allowing identification of the alimentary
      limb, followed by guidewire passage, with radioscopic control. Once the guidewire
      was positioned, stent placement was possible and safe. Upper edge of stent was
      placed in the lower third of the esophagus. RESULTS: Patient progressed
      uneventfully. After 4 weeks, stent removal was attempted. However, it was not
      possible due to endoluminal tissue hyperplasia. Argon plasma was used three times
      to promote proliferative mucosa ablation. Stent was removed after 53 days, with
      no migration. The abdominal drain was removed 1 week later. After 6-months follow
      up, the patient remains asymptomatic. CONCLUSION: Early dehiscence closure was
      observed, without recurrence. The use of partially covered self-expandable
      metallic stent is associated with lower migration rates; however, removal can be
      technically difficult due to tissue hyperplasia.

PMID- 29181743
TI  - Molecular dynamics simulation of bacterial flagella.
AB  - The bacterial flagellum is a biological nanomachine for the locomotion of
      bacteria, and is seen in organisms like Salmonella and Escherichia coli. The
      flagellum consists of tens of thousands of protein molecules and more than 30
      different kinds of proteins. The basal body of the flagellum contains a protein
      export apparatus and a rotary motor that is powered by ion motive force across
      the cytoplasmic membrane. The filament functions as a propeller whose helicity is
      controlled by the direction of the torque. The hook that connects the motor and
      filament acts as a universal joint, transmitting torque generated by the motor to
      different directions. This report describes the use of molecular dynamics to
      study the bacterial flagellum. Molecular dynamics simulation is a powerful method
      that permits the investigation, at atomic resolution, of the molecular mechanisms
      of biomolecular systems containing many proteins and solvent. When applied to the
      flagellum, these studies successfully unveiled the polymorphic supercoiling and
      transportation mechanism of the filament, the universal joint mechanism of the
      hook, the ion transfer mechanism of the motor stator, the flexible nature of the
      transport apparatus proteins, and activation of proteins involved in chemotaxis.

PMID- 29181747
TI  - Unusual accidental decapitation in a road traffic incident.
AB  - Decapitation is an occurrence only rarely encountered in forensic medical
      practice. This fatality is generally most often described in pedestrians who have
      been run over by trains accidently or in cases of suicide, or alternatively in
      occupants of cars involved in high speed vehicle collisions. We report, for the
      first time, a case of a complete decapitation of a pedestrian as a consequence of
      a traffic accident. Due to a thorough medico-legal investigation of the body and
      the involved vehicle, we were able to reconstruct the unique dynamics of the
      accident and the mechanism of injury.

PMID- 29181748
TI  - A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In
      Vitro Experiments.
AB  - There are a growing number of studies that model immunological processes in the
      artery wall that lead to the development of atherosclerotic plaques. However, few
      of these models use parameters that are obtained from experimental data even
      though data-driven models are vital if mathematical models are to become
      clinically relevant. We present the development and analysis of a quantitative
      mathematical model for the coupled inflammatory, lipid and macrophage dynamics in
      early atherosclerotic plaques. Our modeling approach is similar to the
      biologists' experimental approach where the bigger picture of atherosclerosis is
      put together from many smaller observations and findings from in vitro
      experiments. We first develop a series of three simpler submodels which are least
      squares fitted to various in vitro experimental results from the literature.
      Subsequently, we use these three submodels to construct a quantitative model of
      the development of early atherosclerotic plaques. We perform a local sensitivity
      analysis of the model with respect to its parameters that identifies critical
      parameters and processes. Further, we present a systematic analysis of the long
      term outcome of the model which produces a characterization of the stability of
      model plaques based on the rates of recruitment of low-density lipoproteins, high
      density lipoproteins and macrophages. The analysis of the model suggests that
      further experimental work quantifying the different fates of macrophages as a
      function of cholesterol load and the balance between free cholesterol and
      cholesterol ester inside macrophages may give valuable insight into long-term
      atherosclerotic plaque outcomes. This model is an important step toward models
      applicable in a clinical setting.

PMID- 29181749
TI  - Fate and behavior of dissolved organic matter in a submerged anoxic-aerobic
      membrane bioreactor (MBR).
AB  - In this study, the production, composition, and characteristics of dissolved
      organic matter (DOM) in an anoxic-aerobic submerged membrane bioreactor (MBR)
      were investigated. The average concentrations of proteins and carbohydrates in
      the MBR aerobic stage were 3.96 +/- 0.28 and 8.36 +/- 0.89 mg/L, respectively.
      After membrane filtration, these values decreased to 2.9 +/- 0.2 and 2.8 +/- 0.2
      mg/L, respectively. High performance size exclusion chromatograph (HP-SEC)
      analysis indicated a bimodal molecular weight (MW) distribution of DOMs, and that
      the intensities of all the peaks were reduced in the MBR effluent compared to the
      influent. Three-dimensional fluorescence excitation emission matrix (FEEM)
      indicated that fulvic and humic acid-like substances were the predominant DOMs in
      biological treatment processes. Precise identification and characterization of
      low-MW DOMs was carried out using gas chromatography-mass spectrometry (GC-MS).
      The GC-MS analysis indicated that the highest peak numbers (170) were found in
      the anoxic stage, and 54 (32%) compounds were identified with a similarity
      greater than 80%. Alkanes (28), esters (11), and aromatics (7) were the main
      compounds detected. DOMs exhibited both biodegradable and recalcitrant
      characteristics. There were noticeable differences in the low-MW DOMs present
      down the treatment process train in terms of numbers, concentrations, molecular
      weight, biodegradability, and recalcitrance.

PMID- 29181750
TI  - Experimental investigation of urea injection parameters influence on NOx
      emissions from blended biodiesel-fueled diesel engines.
AB  - The present work submits an investigation about the effect of urea injection
      parameters on NOx emissions from a four-stroke four-cylinder diesel engine fueled
      with B20 blended biodiesel. An L9(34) Taguchi orthogonal array was used to design
      the test plan. The results reveal that increasing urea concentration leads to
      lower NOx emissions. Urea flow rate increment has the same influence on NOx
      emission. The same result is obtained by an increase in spray angle. Also,
      according to the analysis of variance (ANOVA), urea concentration and then urea
      flow rate are the most effective design parameters on NOx emissions, while spray
      angle and mixing length have less influence on this pollutant emission. Finally,
      since the result of confirmation test is in good agreement with the predicted
      value based on the Taguchi technique, the predictive capability of this method in
      the present study could be deduced.

PMID- 29181751
TI  - Effect of gasoline fumes on reproductive function in male albino rats.
AB  - The increase in the frequency of exposure to gasoline fumes and the growing
      incidence of infertility among humans has been a major concern and subject of
      discussion over the years in Nigeria. We therefore present the reproductive
      effect of gasoline fumes on inhalation exposure in 40 male albino rats. The rats
      were randomized into five experimental treatments (T) with eight rats per
      treatment. T1 (control) was exposed to distilled water while T2, T3, T4, and T5
      were exposed to gasoline fumes in exposure chambers for 1, 3, 5, and 9 h daily
      respectively for 12 weeks. Serum level of testosterone, follicle stimulating
      hormone (FSH), luteinizing hormone (LH), prolactin, oxidative stress markers in
      the testicular tissue, epididymal sperm health assessment, and testicular
      histopathology of the rats were used as a diagnostic marker of reproductive
      dysfunction. Significant (p < 0.05) alterations in the levels of all the
      reproductive hormones and oxidative stress markers assayed were observed in rats
      exposed to gasoline fume. Significant reductions (p < 0.05) in sperm count and
      percentage motility in the exposed rats were observed. Significant (p < 0.05)
      increased in abnormal sperm cells characterized by damaged head, bent tail,
      damaged tail, and without head were also observed in the exposed rats.
      Histopathologically, severe degenerative testicular architectural lesions
      characterized by alterations in all the generations of sperm cells and reduction
      of interstitial cells were seen in the exposed rats. Gasoline fume is thus said
      to interfere with spermatogenesis and impair fertility in male gonad.

PMID- 29181752
TI  - Phosphate and ammonium adsorption of sesame straw biochars produced at different
      pyrolysis temperatures.
AB  - The adsorption of [Formula: see text] and [Formula: see text] by sesame straw
      biochars (C-300, C-500, and C-700) prepared under different temperatures (300,
      500, and 700  degrees C) was investigated in this study. The physicochemical
      properties of the biochars were characterized using Brunauer-Emmett-Teller
      method, X-ray diffraction, scanning electron microscopy, and Fourier transform
      infrared spectrometry. In batch experiments, C-300 showed the best [Formula: see
      text] adsorption capacity of 3.45 mg/g because of its abundant surface functional
      groups at low pyrolysis temperature. C-700 achieved the optimal [Formula: see
      text] adsorption capacity of 34.17 mg/g because of its high Ca, Mg, and Al
      contents and high surface area at high pyrolysis temperature. The isothermal
      study showed that the Langmuir-Freundlich model could sufficiently describe the
      [Formula: see text] and [Formula: see text] adsorption values, indicating the
      multiple adsorption processes of nutrients on biochars. The maximum [Formula: see
      text] adsorption capacity was 93.61 mg/g on C-300, whereas the maximum [Formula:
      see text] adsorption capacity was as high as 116.58 mg/g on C-700. Kinetic study
      showed that [Formula: see text] adsorption on C-300 was mainly controlled by
      intraparticle diffusion, and the pseudo-second-order model could well describe
      [Formula: see text] adsorption on C-700.

PMID- 29181753
TI  - Characterization of PM2.5 and identification of transported secondary and biomass
      burning contribution in Seoul, Korea.
AB  - The chemical and seasonal characteristics of fine particulates in Seoul, Korea,
      were investigated based on 24-h integrated PM2.5 measurements made over four 1
      month periods in each season between October 2012 and September 2013. The four
      season average concentration of PM2.5 was 37 MUg m-3, and the major chemical
      components were secondary inorganic aerosol (SIA) species of sulfate, nitrate,
      and ammonium (49%), followed by organic matter (34%). The mass concentration and
      most of the chemical components of PM2.5 showed clear seasonal variation, with a
      winter-high and summer-low pattern. The winter-to-summer sulfate ratio and the
      winter organic carbon (OC)-to-elemental carbon (EC) ratio were unusually high
      compared with those in previous studies. Strong correlations of both the sulfate
      level and the sulfur oxidation ratio with relative humidity, and between water
      soluble OC (WSOC) and SIA in winter, suggest the importance of aqueous phase
      chemistry for secondary aerosols. A strong correlation between non-sea salt
      sulfate and Na+ levels, a high Cl-/Na+ ratio, and an unusual positive correlation
      between the nitrogen oxidation ratio and temperature during the winter indicate
      the influence of transported secondary emission sources from upwind urban areas
      and from China across the Yellow Sea. Despite the absence of local forest fires
      and the regulation of wood burning, a high levoglucosan concentration and its
      correlations with OC and WSOC indicate that Seoul was affected by biomass burning
      sources in the winter. The unusually high water-insoluble OC (WIOC)-to-EC ratio
      in winter implies additional transported combustion sources of WIOC. The strong
      correlation between WIOC and levoglucosan suggests the likely influence of
      transported biomass burning sources on the high WIOC/EC ratio during the winter.

PMID- 29181754
TI  - Formulation and characterization of garlic (Allium sativum L.) essential oil
      nanoemulsion and its acaricidal activity on eriophyid olive mites (Acari:
      Eriophyidae).
AB  - Green and nanoacaricides including essential oil (EO) nanoemulsions are important
      compounds to provide new, active, safe acaricides and lead to improvement of
      avoiding the risk of synthetic acaricides. This study was carried out for the
      first time on eriophyid mites to develop nanoemulsion of garlic essential oil by
      ultrasonic emulsification and evaluate its acaricidal activity against the two
      eriophyid olive mites Aceria oleae Nalepa and Tegolophus hassani (Keifer). Acute
      toxicity of nanoemulsion was also studied on male rats. Garlic EO was analyzed by
      gas chromatography-mass spectrometry (GC-MS), and the major compounds were
      diallyl sulfide (8.6%), diallyl disulfide (28.36%), dimethyl tetrasulfide
      (15.26%), trisulfide,di-2-propenyl (10.41%), and tetrasulfide,di-2-propenyl
      (9.67%). Garlic oil nanoemulsion with droplet size 93.4 nm was formulated by
      ultrasonic emulsification for 35 min. Emulsification time and oil and surfactant
      ratio correlated to the emulsion droplet size and stability. The formulated
      nanoemulsion showed high acaricidal activity against injurious eriophyid mites
      with LC50 298.225 and 309.634 MUg/ml, respectively. No signs of nanoemulsion
      toxicity were noted in treating rats; thus, it may be considered non-toxic to
      mammals. Stability of garlic oil nanoemulsion, high acaricidal activity, and the
      absence of organic toxic solvents make the formulation that may be a possible
      acaricidal product. Results suggest the possibility of developing suitable
      natural nanoacaricide from garlic oil.

PMID- 29181755
TI  - Application of the Fenton's process in a bubble column reactor for hydroquinone
      degradation.
AB  - The aim of this study was to assess the degradation and mineralization of
      hydroquinone (HQ) by the Fenton's process in a bubble column reactor (BCR). The
      effect of the main operating variables, namely, air flow rate, effluent volume,
      hydrogen peroxide (H2O2) concentration, catalyst (Fe2+) dose, initial pH, and
      temperature, were assessed. For all air flow rates tested, no concentration
      gradients along the column were noticed, evidencing that a good mixing was
      reached in the BCR. For the best conditions tested ([H2O2] = 500 mg/L, [Fe2+] =
      45 mg/L, T = 24  degrees C, Q air = 2.5 mL/min, pH = 3.0, and V = 5 L), complete
      HQ degradation was reached, with ~ 39% of total organic carbon (TOC) removal, and
      an efficiency of the oxidant use-eta H2O2-of 0.39 (ratio between TOC removed per
      H2O2 consumed normalized by the theoretical stoichiometric value); moreover, a
      non-toxic effluent was generated. Under these conditions, the intermediates and
      final oxidation compounds identified and quantified were a few carboxylic acids,
      namely, maleic, pyruvic, and oxalic. As a strategy to improve the TOC removal, a
      gradual dosage of the optimal H2O2 concentration was implemented, being obtained
      ~ 55% of mineralization (with complete HQ degradation). Finally, the matrix
      effect was evaluated, for which a real wastewater was spiked with 100 mg/L of HQ;
      no reduction in terms of HQ degradation and mineralization was observed compared
      to the solution in distilled water.

PMID- 29181756
TI  - Obstacle diagnosis of green competition promotion: a case study of provinces in
      China based on catastrophe progression and fuzzy rough set methods.
AB  - As "green" and "sustainable" become the new themes of regional economic
      development, green competitiveness will undoubtedly become a new engine for
      regions to solve environmental, resource use, and other global problems to fit
      the new development themes. Unfortunately, the performance of regional green
      competitiveness is not always satisfactory due to various shortcomings. In this
      study, we abandoned the conventional research approach that directly explores the
      factors that promote regional green competitiveness and analyzed, instead, the
      obstacles to green competitiveness among provinces in China. The barrier degree
      was calculated for each obstacle using a catastrophe progression method and fuzzy
      rough set. Results showed that (a) resource and environmental problems have
      become increasingly prominent and have been the most common obstacles to
      promoting green competitiveness of provinces in China and (b) the obstacles to
      improving regional green competitiveness showed spatial differences and
      peculiarity according to the barrier degree. The outcome of the study can help
      policy makers to better understand and prioritize implementation strategies to
      develop effective action and policy interventions toward more successful
      construction of regional green competitiveness.

PMID- 29181757
TI  - Adsorption of aquaculture pollutants using a sustainable biopolymer.
AB  - Intensive aquaculture needs to adopt techniques that are able to contribute
      towards sustainability. Closed systems that employ water recirculation can
      combine intensive production with environmental sustainability, since there is no
      exchange of water or discharge of effluents into the environment. In order to
      achieve this, effective filtration systems are required to ensure that the water
      quality is satisfactory for the cultivation of aquatic organisms. Chitosan, an
      industrial waste material derived from crustacean farming, is a renewable natural
      material that is biodegradable and possesses adsorbent characteristics. In this
      work, chitosan foam was incorporated in filters and was evaluated as an adsorbent
      of aquaculture pollutants, adding value to the material and at the same time
      providing a use for industrial waste. The foam was characterized by scanning
      electron microscopy and energy dispersive spectroscopy, apparent density, and
      water absorption capacity. It was used to remove ammonia, nitrite,
      orthophosphate, and turbidity from aquaculture effluents. The foam consisted of a
      bilayer with smooth and porous sides, which presented low density, flexibility,
      and high water absorption capacity. The best proportion of the foam, in terms of
      the mass of foam per volume of solution (% m v-1), was 0.10, which resulted in
      removal of 32.8, 57.2, 89.5, and 99.9% of ammonia, nitrite, orthophosphate, and
      turbidity, respectively. This biopolymer produced is biodegradable, and when
      saturated with organic compounds from aquaculture, and no longer suitable for
      reuse as a filter material, it can be employed as a fertilizer, hence closing the
      sustainability cycle of the aquaculture production chain.

PMID- 29181758
TI  - Multi-analytical methodology to diagnose the environmental impact suffered by
      building materials in coastal areas.
AB  - This work is focused on the development of an innovative multi-analytical
      methodology to estimate the impact suffered by building materials in coastal
      environments. With the aim of improving the in situ spectroscopic assessment,
      which is often based on XRF and Raman spectrometers, diffuse reflectance infrared
      Fourier transform (DRIFT) spectroscopy was implemented in the diagnosis study. In
      this way, the additional benefits from DRIFT were compared to the usual in situ
      analyses of building materials, which often have interferences from fluorescence
      and reststrahlen effects. The studies were extended to the laboratory scale by MU
      X-ray fluorescence (MU-XRF) cross-section mapping and ion chromatography (IC),
      and the IC quantitative data were employed to develop thermodynamic models using
      the ECOS-RUNSALT program, with the aim of rationalizing the behavior of soluble
      salts with variations in the temperature and the relative humidity (RH). The
      multi-analytical methodology allowed identification of the most significant
      weathering agents and classification of the severity of degradation according to
      the salt content. The suitability of a DRIFT portable device to analyze these
      types of matrices was verified. Although the Kramers-Kronig algorithm correction
      proved to be inadequate to decrease the expected spectral distortions, the
      assignment was successfully performed based on the secondary bands and
      intensification of the overtones and decreased the time needed for in situ data
      collection. In addition, the pollutants' distribution in the samples and the
      possible presence of dangerous compounds, which were not detected during the in
      situ analysis campaigns, provided valuable information to clarify weathering
      phenomena.

PMID- 29181759
TI  - Theoretical investigations on the kinetics of Cl atom initiated reactions of
      series of 1-alkenes.
AB  - The temperature-dependent rate coefficients were calculated for the reactions of
      Cl atoms with propene (R1), 1-butene (R2), 1-pentene (R3), and 1-hexene (R4) over
      the temperature range of 200-400 K. Canonical variational transition state theory
      (CVT) with small curvature tunneling (SCT) and conventional transition state
      theory (CTST) in combination with MP2/6-31G(d,p), MP2/6-31G+(d,p), and MP2/6-311
      + G(d,p) level of theories were used to calculate the kinetic parameters. The
      obtained rate coefficients at 298 K for the reactions of Cl atoms with propene, 1
      butene, 1-pentene, and 1-hexene are 1.36 * 10-10 cm3 molecule-1 s-1, 1.53 * 10-10
      cm3 molecule-1 s-1, 4.61 * 10-10 cm3 molecule-1 s-1, and 4.76 * 10-10 cm3
      molecule-1 s-1, respectively. In all these reactions, strong negative temperature
      dependence was observed over the studied temperature range. Cl atom addition
      across the double bond is the most dominant pathway. The contribution of
      abstraction channels towards their global rate coefficients was observed to be
      increasing from propene to 1-hexane. Atmospheric implications such as effective
      lifetimes and thermodynamic parameters of the test molecules were investigated in
      the present study.

PMID- 29181761
TI  - Different contexts change the impression of animacy.
AB  - The aim of this research was to explore the effect of different spatiotemporal
      contexts on the perceptual saliency of animacy, and the extent of the
      relationship between animacy and other related properties such as emotions and
      intentionality. Paired-comparisons and ratings were used to compare the
      impressions of animacy elicited by a small square moving on the screen, either
      alone or in the context of a second square. The context element was either static
      or moving showing an animate-like or a physical-like trajectory, and the target
      object moved either toward it or away from it. The movement of the target could
      also include animacy cues (caterpillar-like expanding/contracting phases). To
      determine the effect of different contexts on the emergence of emotions and
      intentions, we also recorded and analysed the phenomenological reports of
      participants. The results show that the context significantly influences the
      perception of animacy, which is stronger in dynamic contexts than in static ones,
      and also when the target is moving away from the context element than when it is
      approaching it. The free reports reveal different proportions in emotional or
      intentional attributions in the different conditions: in particular, the "moving
      away" condition is related to negative emotions, while the "approaching"
      condition evokes positive emotions. Overall, the results suggest that animacy is
      a graded concept that can be articulated in more general characteristics, like
      simple aliveness, and more specific ones, like intentions or emotions, and that
      the spatiotemporal contingencies of the context play a crucial role in making
      them evident.

PMID- 29181760
TI  - ATP7B Mutation Detection and Pathogenicity Analysis: One Atypical Case of
      Wilson's Disease with Adrenocortical Insufficiency.
AB  - Wilson's disease (WD) is an autosomal recessive disorder caused by defective
      function of the copper-transporting ATP7B protein. Symptoms are typically related
      to the brain and liver, while endocrinologic abnormalities are rare. Here, we
      reported a 12-year-old female patient that was initially presented with unusual
      skin darkening and low serum level of adrenocorticotropic hormone and diagnosed
      as having adrenocortical insufficiency. We further screened the mutation in ATP7B
      by direct DNA sequencing and found compound heterozygous mutations: a known
      pathogenic mutation in exon8:c.2333G>T (Arg778Leu) inherited from her mother and
      a variant in intron4:c.1707 + 5G>A inherited from her father. To explore the
      pathogenicity of the intronic variant, a minigene splicing assay was used to
      determine the effects of the splicing variant by analyzing reverse transcription
      PCR of ATP7B minigene transcript production. The result indicated that the c.1707
      + 5G>A variant resulted in exon 4 skipping. We herein identified that 1707 + 5G>A
      intron 4 variant is a pathogenic mutation. Molecular genetic analysis and
      laboratory examination definitely confirmed the patient's condition as WD.
      Clinical status improved considerably after penicillamine treatment. Our results
      extended the mutation spectrum of ATP7B gene and highlighted the importance of
      molecular genetic analysis for the accurate diagnosis of atypical WD. WD may have
      diverse presentations and should be considered in children especially presenting
      with adrenocortical insufficiency as initial symptom, and this study highlights
      the importance of screening for hormone abnormal in WD.

PMID- 29181762
TI  - Magnetic immobilization of bacteria using iron oxide nanoparticles.
AB  - Bacterial cell immobilization is a novel technique used in many areas of
      biosciences and biotechnology. Iron oxide nanoparticles have attracted much
      attention in bacterial cell immobilization due to their unique properties such as
      superparamagnetism, large surface area to volume ratio, biocompatibility and easy
      separation methodology. Adhesion is the basis behind many immobilization
      techniques and various types of interactions determine bacterial adhesion.
      Efficiency of bacterial cell immobilization using iron oxide nanoparticles (IONs)
      generally depends on the physicochemical properties of the IONs and surface
      properties of bacterial cells as well as environmental/culture conditions.
      Bacteria exhibit various metabolic responses upon interaction with IONs, and the
      potential applications of iron oxide nanoparticles in bacterial cell
      immobilization will be discussed in this work.

PMID- 29181763
TI  - Isolation and Purification of Condensed Tannin from the Leaves and Branches of
      Prunus cerasifera and Its Structure and Bioactivities.
AB  - Prunus cerasifera has a rich resource and a weak utilization rate and its
      biological functions have been investigated. We found that the contents of total
      phenol (TP) in leaves and branches of Prunus cerasifera were 117.8 +/- 8.8 and
      100.04 +/- 0.9 mg/g, respectively; the contents of soluble condensed tannin (SCT)
      were 73.95 +/- 0.9 and 78.65 +/- 4.1 mg/g, respectively; the structure of SCT
      containing afzelechin/epiafzelechin, catechin/epicatechin, and
      atechin/epicatechin as the main units and the SCT from leaves and branches
      exhibited better anti-tyrosinase and antioxidant activities. This study could
      clarify Prunus cerasifera condensed tannin resource availability and lay a
      theoretical foundation for its development as a natural antioxidant and
      tyrosinase inhibitor.

PMID- 29181764
TI  - Exploring the Degradation of Gallotannins Catalyzed by Tannase Produced by
      Aspergillus niger GH1 for Ellagic Acid Production in Submerged and Solid-State
      Fermentation.
AB  - Due to great interest on producing bioactive compounds for functional foods and
      biopharmaceuticals, it is important to explore the microbial degradation of
      potential sources of target biomolecules. Gallotannins are polyphenols present in
      nature, an example of them is tannic acid which is susceptible to enzymatic
      hydrolysis. This hydrolysis is performed by tannase or tannin acyl hydrolase,
      releasing in this way, biomolecules with high-added value. In the present study,
      chemical profiles obtained after fungal degradation of tannic acid under two
      bioprocesses (submerged fermentation (SmF) and solid state fermentation (SSF))
      were determined. In both fermentation systems (SmF and SSF), Aspergillus niger
      GH1 strain and tannic acid as a sole carbon source and inducer were used (the
      presence of tannic acid promotes production of enzyme tannase). In case of SSF,
      polyurethane foam (PUF) was used like as support of fermentation; culture medium
      only was used in case of submerged fermentation. Fermentation processes were
      monitored during 72 h; samples were taken kinetically every 8 h; and all extracts
      obtained were partially purified to obtain polyphenolic fraction and then were
      analyzed by liquid chromatography-mass spectrometry (LC-MS). Molecules like
      gallic acid and n-galloyl glucose were identified as intermediates in degradation
      of tannic acid; during SSF was identified ellagic acid production. The results
      obtained in this study will contribute to biotechnological production of ellagic
      acid.

PMID- 29181765
TI  - Periorbital actinomycosis masquerading as a cutaneous malignancy.

PMID- 29181766
TI  - Reply to: metoprolol, or propranolol, or carvedilol, or labetalol, for patients
      with takotsubo syndrome?

PMID- 29181767
TI  - Frailty, diabetes, and the convergence of chronic disease in an age-related
      condition: a population-based nationwide cross-sectional analysis of the Mexican
      nutrition and health survey.
AB  - AIMS: To describe the associations of frailty with diabetes mellitus and related
      conditions in older adults. METHODS: We conducted a cross-sectional analysis of a
      representative sample of older adults (n = 5379). We generated a 35-item frailty
      index (FI) and obtained information on diabetes and related conditions
      (peripheral neuropathy, lower limb amputation, diabetic coma, number of physician
      visits due to diabetes-related conditions, all-cause hospitalizations in the past
      year, years since diabetes diagnosis, and type of treatment). Logistic and
      Poisson regression models were used to determine the associations between frailty
      and diabetes and its complications. RESULTS: The mean age was 70.3 years (+/-
      7.8); 54.7% were women. Those with an FI <= 0.082 composed the reference group.
      Multivariate analysis showed an OR of 2.32 (95% CI 1.93-2.73, p < 0.001) for the
      association between diabetes and frailty. People who were hospitalized for any
      cause during the previous year, those receiving both insulin and an oral compound
      to manage diabetes, and those with peripheral neuropathy showed ORs of 2.32 (95%
      CI 1.69-3.18, p < 0.001), 5.6 (95% CI 1.58-19.8, p = 0.008), and 2.02 (95% CI
      1.42-2.86, p < 0.001), respectively, for being in the most frail group.
      CONCLUSIONS: People with diabetes have higher frailty scores. Furthermore, older
      adults with diabetes and higher burden of frailty have more diabetes-related
      complications.

PMID- 29181768
TI  - Identification and feasibility of social participation initiatives reducing
      isolation and involving rural older Canadians in the development of their
      community.
AB  - BACKGROUND: Although some social participation initiatives exist to counter the
      isolation of older adults, none were identified and prioritized according to the
      needs of rural regional county municipalities (RCM), including in Canada. AIMS:
      To identify and prioritize social participation initiatives for older Canadians,
      and to document the feasibility of their implementation in a rural RCM. METHODS:
      An action research was used to identify, based on a review of scientific and grey
      literature, social participation initiatives, enriched and prioritized by the
      community. Facilitators, challenges, and advice for the implementation of these
      initiatives were documented through nine group discussions (n = 85). RESULTS: Two
      social participation initiatives were identified as more relevant to the RCM,
      combined and adapted as the Benevolent Community to locate and assist isolated
      older adults. Two other initiatives were prioritized to identify transportation
      needs and solutions, and create a website on social participation activities
      available. Most participants perceived these initiatives as feasible, and will
      address older adults' social participation needs. Two facilitators were a field
      worker for older adults and the preoccupations of the community toward isolated
      older adults. The main challenges concerned the difficulty in recruiting
      volunteers and locating isolated older adults, exacerbated by the RCM's vast
      territory. Main advice involved suggestions of people for the recruitment of
      volunteers. DISCUSSION: Through valuable collaboration with the community,
      initiatives were identified and prioritized, and challenges were raised, with
      anticipated success. CONCLUSIONS: Further studies are needed to document the
      implementation and effects of these initiatives on the social participation of
      older adults in the RCM.

PMID- 29181769
TI  - Cognitive functioning, subjective memory complaints and risky behaviour predict
      minor home injuries in elderly.
AB  - INTRODUCTION: Home accidents are one of the major causes of death, particularly
      in older people, young children and women. AIMS: The first aim of this study was
      to explore the role of subjective memory complaints, cognitive functioning and
      risky behaviour as predictors of home injuries occurred in a year in a sample of
      healthy Italian older adults. The second aim was to investigate the role of risky
      behaviour as a mediator in the relationship between subjective and objective
      cognitive functioning and home injuries. METHODS: One hundred thirty-three
      community-dwelling older people from southern Italy were administered a battery
      of tests to evaluate cognitive functioning, subjective memory complaints, and
      risky behaviour during home activities. Risky behaviour was evaluated using the
      Domestic Behaviour Questionnaire, created specifically for this purpose. The
      number of home injuries was recorded for a year throughout monthly telephone
      interviews. A path analysis was performed to test the following model: cognitive
      functioning and subjective memory complaints directly influence risky behaviour
      and number of accidents over a year; risky behaviour mediates the impact of
      cognitive functioning and subjective memory on number of accidents over a year.
      RESULTS: Path analysis confirmed the model tested except the role of risky
      behaviour as a mediator between cognitive functioning and home accidents.
      DISCUSSION: Risky behaviour could represent a further risk factor in cognitively
      intact older adults with subjective memory complaints. CONCLUSIONS: The
      assessment of both cognition and behaviour in elderly can make a valuable
      contribution in preventing home accidents in elderly.

PMID- 29181770
TI  - A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate.
AB  - Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million
      people worldwide. Major shortcomings in clinical translation result from multiple
      factors, including species differences, development of moderately predictive
      animal models, and differences in methodologies between preclinical and clinical
      studies. To overcome these obstacles, we first conducted a comparative
      neuroanatomical analysis of the spinal cord between mice, Microcebus murinus (a
      nonhuman primate), and humans. Next, we developed and characterized a new model
      of lateral spinal cord hemisection in M. murinus. Over a 3-month period after
      SCI, we carried out a detailed, longitudinal, behavioral follow-up associated
      with in vivo magnetic resonance imaging (1H-MRI) monitoring. Then, we compared
      lesion extension and tissue alteration using 3 methods: in vivo 1H-MRI, ex vivo
      1H-MRI, and classical histology. The general organization and glial cell
      distribution/morphology in the spinal cord of M. murinus closely resembles that
      of humans. Animals assessed at different stages following lateral hemisection of
      the spinal cord presented specific motor deficits and spinal cord tissue
      alterations. We also found a close correlation between 1H-MRI signal and
      microglia reactivity and/or associated post-trauma phenomena. Spinal cord
      hemisection in M. murinus provides a reliable new nonhuman primate model that can
      be used to promote translational research on SCI and represents a novel and more
      affordable alternative to larger primates.

PMID- 29181771
TI  - Correction to: SPG7 and Impaired Emotional Communication.
AB  - The original version of this article unfortunately contained an incorrect
      assignment of affiliations of Linwei Zhang and Tetsuo Ashizawa.

PMID- 29181773
TI  - Budget Impact Analysis of PCSK9 Inhibitors for the Management of Adult Patients
      with Heterozygous Familial Hypercholesterolemia or Clinical Atherosclerotic
      Cardiovascular Disease.
AB  - OBJECTIVE: The aim of this study was to assess the budget impact of introducing
      the proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) alirocumab
      and evolocumab to market for the treatment of adults with heterozygous familial
      hypercholesterolemia or clinical atherosclerotic cardiovascular (CV) disease
      requiring additional lowering of low-density lipoprotein cholesterol (LDL-C).
      METHODS: A 3-year model estimated the costs of lipid-modifying therapy (LMT) and
      CV events to a hypothetical US health plan of 1 million members, comparing two
      scenarios-with and without the availability of PCSK9i as add-on therapy to
      statins. Proportions of patients with uncontrolled LDL-C despite receiving
      statins, and at risk of CV events, were estimated from real-world data. Total
      undiscounted annual LMT costs (2017 prices, including PCSK9i costs of
      $14,563.50), dispensing and healthcare costs, including the costs of CV events,
      were estimated for all prevalent patients in the target population, based on
      baseline risk factors. Maximum PCSK9i utilization of 1-5% over 3 years according
      to risk group (following the same pattern as current ezetimibe use), and 5-10% as
      a secondary scenario, were assumed. RESULTS: Total healthcare budget impacts per
      target patient (and per member) per month for years 1, 2 and 3 were $3.62($0.10),
      $7.22($0.20) and $10.79($0.30), respectively, assuming 1-5% maximum PCSK9i
      utilization, and $15.81($0.44), $31.52($0.88) and $47.12($1.31), respectively,
      assuming 5-10% utilization. Results were sensitive to changes in model timeframe,
      years to maximum PCSK9i utilization and PCSK9i costs. CONCLUSIONS: The budget
      impact of PCSK9i as add-on therapy to statins for patients with
      hypercholesterolemia is relatively low compared with published estimates for
      other specialty biologics. Drug cost rebates and discounts are likely to further
      reduce budget impact.

PMID- 29181772
TI  - Liver cell therapy: is this the end of the beginning?
AB  - The prevalence of liver diseases is increasing globally. Orthotopic liver
      transplantation is widely used to treat liver disease upon organ failure. The
      complexity of this procedure and finite numbers of healthy organ donors have
      prompted research into alternative therapeutic options to treat liver disease.
      This includes the transplantation of liver cells to promote regeneration. While
      successful, the routine supply of good quality human liver cells is limited.
      Therefore, renewable and scalable sources of these cells are sought. Liver
      progenitor and pluripotent stem cells offer potential cell sources that could be
      used clinically. This review discusses recent approaches in liver cell
      transplantation and requirements to improve the process, with the ultimate goal
      being efficient organ regeneration. We also discuss the potential off-target
      effects of cell-based therapies, and the advantages and drawbacks of current pre
      clinical animal models used to study organ senescence, repopulation and
      regeneration.

PMID- 29181774
TI  - Sequestering of damage-associated molecular patterns (DAMPs): a possible
      mechanism affecting the immune-stimulating properties of aluminium adjuvants.
AB  - Aluminium-based adjuvants (ABAs) have been used in human and veterinary vaccines
      for decades, and for a long time, the adjuvant properties were believed to be
      mediated by an antigen depot at the injection site, prolonging antigen exposure
      to the immune system. The depot hypothesis is today more or less abandoned, and
      instead replaced by the assumption that ABAs induce an inflammation at the
      injection site. Induction of an inflammatory response is consistent with immune
      activation initiated by recognition of molecular patterns associated with danger
      or damage (DAMPs), and the latter are derived from endogenous molecules that
      normally reside intracellularly. When extracellularly expressed, because of
      damage, stress or cell death, a sterile inflammation is induced. In this paper,
      we report the induction of DAMP release by viable cells after phagocytosis of
      aluminium-based adjuvants. Two of the most commonly used ABAs in pharmaceutical
      vaccine formulations, aluminium oxyhydroxide and aluminium hydroxyphosphate,
      induced a vigorous extracellular expression of the two DAMP molecules
      calreticulin and HMGB1. Concomitantly, extracellular adjuvant particles adsorbed
      the DAMP molecules released by the cells whereas IL-1beta, a previously reported
      inflammatory mediator induced by ABAs, was not absorbed by the adjuvants.
      Induction of extracellular expression of the two DAMP molecules was more
      prominent using aluminium hydroxyphosphate compared to aluminium oxyhydroxide,
      whereas the extracellular adsorption of the DAMP molecules was more pronounced
      with the latter. Furthermore, it is hypothesised how induction of DAMP expression
      by ABAs and their concomitant adsorption by extracellular adjuvants may affect
      the inflammatory properties of ABAs.

PMID- 29181775
TI  - Notch ligand Delta-like1 enhances degranulation and cytokine production through a
      novel Notch/Dok-1/MAPKs pathway in vitro.
AB  - Food allergy includes sensitization phase and effect phase, and effect cells
      degranulate and secrete cytokines in the effect phase, causing allergic clinical
      symptoms. We have demonstrated that Notch signaling plays an important role in
      the sensitization phase, but its role in effect phases still remains unclear. In
      this study, we investigated the role of Notch signaling in degranulation and
      cytokine production of the effect phase response. A RBL-2H3 cell model was used
      and Notch signaling was induced by priming with Notch ligands. Our results showed
      after priming with Notch ligand, Delta-like1(Dll1)-Fc, beta-hexosaminidase
      release, and cytokines production, including TGF-beta, IL-1beta, IL-4, IL-6, and
      IL-13, were increased significantly, and the enhancement was abolished after DAPT
      treatment, a gamma-secretase inhibitor, indicating that Dll1 Notch signaling
      enhanced RBL-2H3 cell degranulation and cytokine production. Western blot
      analysis showed that Dll1 Notch signaling augmented high-affinity IgE receptors
      mediated phosphorylation of MAPKs through suppressing the expression of
      downstream tyrosine kinases 1 (Dok-1). Besides, a passive systemic anaphylaxis
      mouse model was used to confirm the role of Notch signaling. And our data showed
      that allergic clinical features of mice were alleviated, and the level of
      degranulation was decreased significantly after inhibiting Notch signaling in
      vivo. Therefore, we demonstrated Notch ligand Dll1 enhanced RBL-2H3 cell
      degranulation and cytokine production through a novel Notch/Dok-1/MAPKs pathway,
      suggesting Notch signaling played a key role in the effect phase of food allergy.

PMID- 29181776
TI  - [Detection and prevention in later life: risk profiles for physical,
      psychological, social and environmental frailty.]
AB  - In order to provide proactive care and support for older people attention is
      needed for the prevention of frailty among older adults. Subsequently, accurate
      case finding of those who are more at risk of becoming frail is crucial to
      undertake specific preventive actions. This study investigates frailty and risk
      profiles of frailty among older people in order to support proactive detection.
      Hereby, frailty is conceived not only as a physical problem, but also refers to
      emotional, social, and environmental hazards. Using data generated from the
      Belgian Ageing Studies (N = 21,664 home-dwelling older people), a multinomial
      logistic regression model was tested which included socio-demographic and socio
      economic indicators as well as the four dimensions of frailty (physical, social,
      psychological and environmental). Findings indicate that for both men and women
      having moved in the previous 10 years and having a lower household income are
      risk factors of becoming multidimensional frail. However, studying the different
      frailty domains, several risk profiles arise (e. g. marital status is important
      for psychological frailty), and gender-specific risk groups are detected (e. g.
      non-married men). This paper elaborates on practical implications and formulates
      a number of future research recommendations to tackle frailty in an ageing
      society.

PMID- 29181777
TI  - The utilization of fluorescent cholangiography during robotic cholecystectomy at
      an inner-city academic medical center.
AB  - In recent years, fluorescent cholangiography using Indocyanine green (ICG) dye
      has been used to aid identification of structures during robotic cholecystectomy.
      We sought to compare cholecystectomy with ICG dye versus laparoscopic
      cholecystectomy at an inner-city academic medical center. Between January 2013
      and July 2016, we identified 287 patients of which 191 patients underwent
      laparoscopic cholecystectomy and 96 patients underwent robotic cholecystectomy
      with ICG dye. Preoperative risk variables of interest included age, sex, race,
      body mass index (BMI), and acute cholecystitis. Primary outcome of interest was
      conversion to open procedures while secondary outcome was length of stay. The two
      groups were similar in their BMI (31.98 vs. 31.10 kg/m2 for the laparoscopic and
      robotic, respectively, p = 0.32). The laparoscopic group had a greater mean age
      compared to the robotic group (47.77 vs. 43.61 years, p = 0.04). There was no
      significant difference in sex and emergency surgery between the two groups. Fewer
      open conversions were found in the robotic than the laparoscopic group [2 (2.1%)
      vs. 17 (8.9%), p = 0.03]. In multiple logistic regression, robotic
      cholecystectomy with ICG also showed a lower risk of conversion compared to
      laparoscopic cholecystectomy, but the difference did not reach statistical
      significance (OR 0.42, 95% CI 0.11-1.65, p = 0.22). ICG fluorescent
      cholangiography during robotic cholecystectomy may contribute to proper
      identification of biliary structures and may reduce the rates of open conversion.
      The preliminary results of fewer open conversions are promising. Further studies
      with a large randomized prospective controlled study should be taken for further
      evaluation.

PMID- 29181778
TI  - Retzius space reconstruction following transperitoneal laparoscopic robot
      assisted radical prostatectomy: does it have any added value?
AB  - Retzius space sparing (RSS) during laparoscopic robot-assisted radical
      prostatectomy (RALP) has been offered as an approach that reduces perioperative
      complications and enables faster gaining of full urinary continence due to
      bladder anatomy preservation. Retro and transperitoneal techniques have been
      proposed, whereby RSS has been implemented. We sought to explore whether Retzius
      space reconstruction (RSR) following transperitoneal RALP will be an advantageous
      step as well. A prospective registry database of 102 consecutive transperitoneal
      RALP cases performed by a single surgeon was reviewed. The Retzius space had been
      opened by dissecting the bladder away from the anterior abdominal wall to the
      level of both internal rings. In the last 51 cases (RSR group), the peritoneal
      layer had been sutured back, thus repositioning the bladder back to the anterior
      abdominal wall and reconstructing the Retzius space. Perioperative factors were
      analyzed and compared between the two groups. Demographic and perioperative data
      did not differ between the two groups. RSR group demonstrated shorter length of
      stay (LOS) compared with the control group (p = 0.01), as well as faster urinary
      continence recovery (i.e., 0 pads) (p = 0.01). Moreover, lower numbers of Clavien
      Dindo class 3 complications and 12 mm port-site hernias (p = 0.03) were seen in
      the RSR group compared with the control group. RSR following transperitoneal RALP
      is a simple and efficient step that potentially reduces early and late post
      operative complications, shortens LOS and accelerates full urinary continence.

PMID- 29181779
TI  - Linking Individuals with Substance Use Disorders (SUDs) in Primary Care to SUD
      Treatment: the Recovery Management Checkups-Primary Care (RMC-PC) Pilot Study.
AB  - Linking individuals in primary care settings with substance use disorders (SUDs)
      to SUD treatment has proven to be challenging, despite the widespread use of
      Screening, Brief Intervention, and Referral to Treatment (SBIRT). This paper
      reports findings from a pilot study that examined the efficacy of the Recovery
      Management Checkups intervention adapted for primary care settings (RMC-PC), for
      assertively linking and engaging patients from Federally Qualified Health Centers
      into SUD treatment. Findings showed that patients in the RMC-PC (n=92) had
      significantly higher rates of SUD treatment entry and received more days of SUD
      treatment compared with those who receive the usual SBIRT referral (n=50).
      Receipt of RMC-PC had both direct and indirect effects, partially mediated
      through days of SUD treatment, on reducing days of drug use at 6 months post
      intake. RMC-PC is a promising intervention to address the need for more assertive
      methods for linking patients in primary care to SUD treatment.

PMID- 29181781
TI  - Recognition of transposed melodies: Effects of pitch distance and harmonic
      distance.
AB  - People easily recognize a familiar melody in a previously unheard key, but they
      also retain some key-specific information. Does the recognition of a transposed
      melody depend on either pitch distance or harmonic distance from the initially
      learned instances? Previous research has shown a stronger effect of pitch
      closeness than of harmonic similarity, but did not directly test for an
      additional effect of the latter variable. In the present experiment, we
      familiarized participants with a simple eight-note melody in two different keys
      (C and D) and then tested their ability to discriminate the target melody from
      foils in other keys. The transpositions included were to the keys of C# (close in
      pitch height, but harmonically distant), G (more distant in pitch, but
      harmonically close), and F# (more distant in pitch and harmonically distant).
      Across participants, the transpositions to F# and G were either higher or lower
      than the initially trained melodies, so that their average pitch distances from C
      and D were equated. A signal detection theory analysis confirmed that
      discriminability (d') was better for targets and foils that were close in pitch
      distance to the studied exemplars. Harmonic similarity had no effect on
      discriminability, but it did affect response bias (c), in that harmonic
      similarity to the studied exemplars increased both hits and false alarms. Thus,
      both pitch distance and harmonic distance affect the recognition of transposed
      melodies, but with dissociable effects on discrimination and response bias.

PMID- 29181780
TI  - 3D-Models of Insulin-Producing beta-Cells: from Primary Islet Cells to Stem Cell
      Derived Islets.
AB  - There is a need for physiologically relevant assay platforms to provide
      functionally relevant models of diabetes, to accelerate the discovery of new
      treatment options and boost developments in drug discovery. In this review, we
      compare several 3D-strategies that have been used to increase the functional
      relevance of ex vivo human primary pancreatic islets and developments into the
      generation of stem cell derived pancreatic beta-cells (beta-cells). Special
      attention will be given to recent approaches combining the use of extracellular
      matrix (ECM) scaffolds with pancreatic molecular memory, which can be used to
      improve yield and functionality of in vitro stem cell-derived pancreatic models.
      The ultimate goal is to develop scalable cell-based platforms for diabetes
      research and drug screening. This article will critically assess key aspects
      related to in vitro pancreatic 3D-ECM models and highlight the most promising
      approaches for future research.

PMID- 29181782
TI  - When attention is intact in adults with ADHD.
AB  - Is covert visuospatial attention-selective processing of information in the
      absence of eye movements-preserved in adults with attention-deficit/hyperactivity
      disorder (ADHD)? Previous findings are inconclusive due to inconsistent
      terminology and suboptimal methodology. To settle this question, we used well
      established spatial cueing protocols to investigate the perceptual effects of
      voluntary and involuntary attention on an orientation discrimination task for a
      group of adults with ADHD and their neurotypical age-matched and gender-matched
      controls. In both groups, voluntary attention significantly improved accuracy and
      decreased reaction times at the relevant location, but impaired accuracy and
      slowed reaction times at irrelevant locations, relative to a distributed
      attention condition. Likewise, involuntary attention improved accuracy and
      speeded responses. Critically, the magnitudes of all these orienting and
      reorienting attention effects were indistinguishable between groups. Thus, these
      counterintuitive findings indicate that spatial covert attention remains
      functionally intact in adults with ADHD.

PMID- 29181783
TI  - Capnocytophaga endodontalis sp. nov., Isolated from a Human Refractory Periapical
      Abscess.
AB  - A novel Gram-negative, capnophilic, fusiform bacterium, designated strain ChDC
      OS43T, was isolated from a human refractory periapical abscess in the left
      mandibular second molar and was characterized by polyphasic taxonomic analysis.
      The 16S rRNA gene sequence revealed that the strain belongs to the genus
      Capnocytophaga, as it showed sequence similarities to Capnocytophaga ochracea
      ATCC 27872T (96.30%) and C. sputigena ATCC 33612T (96.16%). The prevalent fatty
      acids of strain ChDC OS43T were isoC15:0 (57.54%), C16:0 (5.93%), C16:0 3OH
      (5.72%), and C18:1 cis 9 (4.41%). The complete genome of strain ChDC OS43T was
      3,412,686 bp, and the G+C content was 38.2 mol%. The average nucleotide identity
      (ANI) value between strain ChDC OS43T and C. ochracea ATCC 27872T or C. sputigena
      ATCC 33612T was >92.01%. The genome-to-genome distance (GGD) value between strain
      ChDC OS43T and C. ochracea ATCC 27872T or C. sputigena ATCC 33612T was 32.0 and
      45.7%, respectively. Based on the results of phenotypic, chemotaxonomic, and
      phylogenetic analysis, strain ChDC OS43T (= KCOM 1579T = KCTC 5562T = KCCM 42841T
      = JCM 32133T) should be classified as the type strain of a novel species of genus
      Capnocytophaga, for which the name Capnocytophaga endodontalis sp. nov. is
      proposed.

PMID- 29181784
TI  - Reply to responsible growth of nuclear cardiology in Spain.

PMID- 29181785
TI  - Multimodality imaging: Bird's eye view from The American College of Cardiology
      Annual Scientific Meeting 2017, Washington DC March 17 to 19, 2017.

PMID- 29181786
TI  - Early therapeutic effects of adaptive servo-ventilation on cardiac sympathetic
      nervous function in patients with heart failure evaluated using a combination of
      11C-HED PET and 123I-MIBG SPECT.
AB  - RATIONALE: Adaptive servo-ventilation (ASV), a novel respiratory support therapy
      for sleep disorders, may improve cardiac function in heart failure (HF). However,
      the reasons that ASV improves cardiac function have not been fully studied
      especially in sympathetic nervous function (SNF). The purpose of the present
      study was to investigate the effects of ASV therapy on cardiac SNF in patients
      with HF. METHODS: We evaluated ASV therapeutic effects before and 6 months after
      ASV therapy in 9 HF patients [57.3 +/- 17.3 years old, left ventricular ejection
      fraction (LVEF) 36.1 +/- 16.7%]. We performed echocardiography, polysomnography,
      biomarkers, 11C-hydroxyephedrine (HED) PET as a presynaptic function marker and
      planar 123I-metaiodobenzylguanidine (MIBG) to evaluate washout rate. RESULTS: ASV
      therapy reduced apnea-hypopnea index (AHI) and improved plasma brain natriuretic
      peptide (BNP) concentration. In 123I-MIBG imaging, the early heart/mediastinum
      (H/M) ratio increased after ASV therapy (2.19 +/- 0.58 to 2.40 +/- 0.67; P =
      0.045). Washout rate did not change (23.8 +/- 7.3% to 23.8 +/- 8.8%; P = 0.122).
      Global 11C-HED retention index (RI) improved from 0.068 +/- 0.033/s to 0.075 +/-
      0.034/s (P = 0.029). CONCLUSIONS: ASV reduced AHI and improved BNP. ASV might
      initially improve presynaptic cardiac sympathetic nervous function in HF patients
      after 6 months of treatment.

PMID- 29181787
TI  - What Does 'Unpaid Consultant' Signify? A Survey of Euphemistic Language in
      Conflict of Interest Declarations.
AB  - BACKGROUND AND OBJECTIVE: Inadequate competing interest declarations present
      interpretive challenges for editors, reviewers, and readers. We systematically
      studied a common euphemism, 'unpaid consultant,' to determine its occurrence in
      declarations and its association with vested interests, authors, and journals.
      METHODS: We used Google Scholar, a search engine that routinely includes
      disclosures, to identify 1164 occurrences and 787 unique biomedical journal
      publications between 1994 and 2014 that included one or more authors declaring
      themselves as an "unpaid consultant." Changes over time were reckoned with
      absolute and relative yearly rates, the latter normalized by overall biomedical
      publication volumes. We further analyzed declarations according to author,
      consultancy recipient, and journal. RESULTS: We demonstrate increases in the use
      of "unpaid consultant" since 2004 and show that such uninformative declarations
      are overwhelmingly (801/865, 92.6%) associated with for-profit companies and
      other vested interests, most notably in the pharmaceutical, device, and biotech
      industries. CONCLUSIONS: Disclosing 'unpaid' relationships with for-profit
      companies typically signals but does not explain competing interests. Our
      findings challenge editors to respond to the increasing use of language that may
      conceal rather than illuminate conflicts of interest.

PMID- 29181788
TI  - Mortality Associated with Metformin Versus Sulfonylurea Initiation: A Cohort
      Study of Veterans with Diabetes and Chronic Kidney Disease.
AB  - BACKGROUND: For patients with type 2 diabetes and chronic kidney disease (CKD),
      high-quality evidence about the relative benefits and harms of oral glucose
      lowering drugs is limited. OBJECTIVE: To evaluate whether mortality risk differs
      after the initiation of monotherapy with either metformin or a sulfonylurea in
      Veterans with type 2 diabetes and CKD. DESIGN: Observational, national cohort
      study in the Veterans Health Administration (VHA). PARTICIPANTS: Veterans who
      received care from the VHA for at least 1 year prior to initiating monotherapy
      treatment for type 2 diabetes with either metformin or a sulfonylurea between
      2004 and 2009. MAIN MEASURES: Metformin and sulfonylurea use was assessed from
      VHA electronic pharmacy records. The CKD-EPI equation was used to estimate
      glomerular filtration rate (eGFR). The outcome of death from January 1, 2004,
      through December 31, 2009, was assessed from VHA Vital Status files. KEY RESULTS:
      Among 175,296 new users of metformin or a sulfonylurea monotherapy, 5121 deaths
      were observed. In primary analyses adjusted for all measured potential
      confounding factors, metformin monotherapy was associated with a lower mortality
      hazard ratio (HR) compared with sulfonylurea monotherapy across all ranges of
      eGFR evaluated (HR ranging from 0.59 to 0.80). A secondary analysis of mortality
      risk differences favored metformin across all eGFR ranges; the greatest risk
      difference was observed in the eGFR category 30-44 mL/min/1.73m2 (12.1 fewer
      deaths/1000 person-years, 95% CI 5.2-19.0). CONCLUSIONS: Initiation of metformin
      versus a sulfonylurea among individuals with type 2 diabetes and CKD was
      associated with a substantial reduction in mortality, in terms of both relative
      and absolute risk reduction. The largest absolute risk reduction was observed
      among individuals with moderately-severely reduced eGFR (30-44 mL/min/1.73m2).

PMID- 29181789
TI  - Capsule Commentary on Merlin et al., Managing Concerning Behaviors in Patients
      Prescribed Opioids for Chronic Pain: A Delphi Study.

PMID- 29181790
TI  - Improving Outcomes After Hospitalization: A Prospective Observational Multicenter
      Evaluation of Care Coordination Strategies for Reducing 30-Day Readmissions to
      Maryland Hospitals.
AB  - BACKGROUND: Patients frequently experience suboptimal transitions from the
      hospital to the community, which can increase the likelihood of readmission. It
      is not known which care coordination services can lead to improvements in
      readmission rates. OBJECTIVE: To evaluate the effects of two care coordination
      interventions on 30-day readmission rates. DESIGN: Prospective multicenter
      observational study of hospitalized patients eligible for two care coordination
      services between January 1, 2013, and October 31, 2015. Readmission rates were
      compared for patients who received each care coordination intervention versus
      those who did not using multivariable generalized estimating equation logistic
      regression models. PARTICIPANTS: A total of 25,628 patients hospitalized in
      medicine, neurosciences, or surgical sciences units. INTERVENTIONS: Patients
      discharged home and deemed to be at high risk for readmission were assigned a
      nurse Transition Guide (TG) for 30 days post-discharge. All other patients were
      assigned the Patient Access Line (PAL) intervention, which provided a post
      discharge phone call from a registered nurse. SETTING: Two large academic
      hospitals in Baltimore, MD. MAIN MEASURES: Thirty-day all-cause readmission to
      any Maryland hospital. KEY RESULTS: Among all patients, 14.2% (2409/16,993) of
      those referred for the PAL intervention and 22.8% (1973/8635) of those referred
      for the TG intervention were readmitted. PAL-referred patients who did not
      receive the intervention had an adjusted odds ratio (aOR) for readmission of 1.27
      (95% confidence interval [95% CI] 1.12-1.44, p < 0.001) compared with patients
      who did. TG-referred patients who did not receive the TG intervention had an aOR
      of 1.83 (95% CI 1.60-2.10, p < 0.001) compared with patients who received the
      intervention. Younger age, male sex, having more comorbidities, and being
      discharged from a medicine unit were associated with not receiving an assigned
      intervention. These characteristics were also associated with higher readmission
      rates. CONCLUSIONS: PAL and TG care coordination interventions were associated
      with lower rates of 30-day readmission. Our findings underscore the importance of
      determining the appropriate intervention for the hardest-to-reach patients, who
      are also at the highest risk of being readmitted.

PMID- 29181791
TI  - Recruiting Rural Healthcare Providers Today: a Systematic Review of Training
      Program Success and Determinants of Geographic Choices.
AB  - BACKGROUND: Rural areas have historically struggled with shortages of healthcare
      providers; however, advanced communication technologies have transformed rural
      healthcare, and practice in underserved areas has been recognized as a policy
      priority. This systematic review aims to assess reasons for current providers'
      geographic choices and the success of training programs aimed at increasing rural
      provider recruitment. METHODS: This systematic review (PROSPERO: CRD42015025403)
      searched seven databases for published and gray literature on the current cohort
      of US rural healthcare practitioners (2005 to March 2017). Two reviewers
      independently screened citations for inclusion; one reviewer extracted data and
      assessed risk of bias, with a senior systematic reviewer checking the data;
      quality of evidence was assessed using the GRADE approach. RESULTS: Of 7276
      screened citations, we identified 31 studies exploring reasons for geographic
      choices and 24 studies documenting the impact of training programs. Growing up in
      a rural community is a key determinant and is consistently associated with
      choosing rural practice. Most existing studies assess physicians, and only a few
      are based on multivariate analyses that take competing and potentially correlated
      predictors into account. The success rate of placing providers-in-training in
      rural practice after graduation, on average, is 44% (range 20-84%; N = 31
      programs). We did not identify program characteristics that are consistently
      associated with program success. Data are primarily based on rural tracks for
      medical residents. DISCUSSION: The review provides insight into the relative
      importance of demographic characteristics and motivational factors in determining
      which providers should be targeted to maximize return on recruitment efforts.
      Existing programs exposing students to rural practice during their training are
      promising but require further refining. Public policy must include a specific
      focus on the trajectory of the healthcare workforce and must consider alternative
      models of healthcare delivery that promote a more diverse, interdisciplinary
      combination of providers.

PMID- 29181792
TI  - Medicaid Expansion, Mental Health, and Access to Care among Childless Adults with
      and without Chronic Conditions.
AB  - BACKGROUND: While the Affordable Care Act's (ACA) Medicaid expansion has
      increased insurance coverage, its effects on health outcomes have been mixed.
      This may be because previous research did not disaggregate mental and physical
      health or target populations most likely to benefit. OBJECTIVE: To examine the
      association between Medicaid expansion and changes in mental health, physical
      health, and access to care among low-income childless adults with and without
      chronic conditions. DESIGN: We used a difference-in-differences analytical
      framework to assess differential changes in self-reported health outcomes and
      access to care. We stratified our analyses by chronic condition status.
      PARTICIPANTS: Childless adults, aged 18-64, with incomes below 138% of the
      federal poverty level in expansion (n = 69,620) and non-expansion states (n =
      57,628). INTERVENTION: Active Medicaid expansion in state of residence. MAIN
      MEASURES: Self-reported general health; total days in past month with poor
      health, poor mental health, poor physical health, or health-related activity
      restrictions; disability; depression; insurance coverage; cost-related barriers;
      annual check-up; and personal doctor. KEY RESULTS: Medicaid expansion was
      associated with reductions in poor health days (-1.2 days [95% CI, -1.6,-0.7])
      and days limited by poor health (-0.94 days [95% CI, -1.4,-0.43]), but only among
      adults with chronic conditions. Trends in general health measures appear to be
      driven by fewer poor mental health days (-1.1 days [95% CI, -1.6,-0.6]).
      Expansion was also associated with a reduction in depression diagnoses (-3.4
      percentage points [95% CI, -6.1,-0.01]) among adults with chronic conditions.
      Expansion was associated with improvements in access to care for all adults.
      CONCLUSIONS: Medicaid expansion was associated with substantial improvements in
      mental health and access to care among low-income adults with chronic conditions.
      These positive trends are likely to be reversed if Medicaid expansion is
      repealed.

PMID- 29181793
TI  - In reply: Eye taping and chlorhexidine exposure: caution when interpreting scarce
      evidence.

PMID- 29181794
TI  - Comparing the socioeconomic status of critical care doctors and patients.

PMID- 29181795
TI  - Comparison of 3D Echocardiogram-Derived 3D Printed Valve Models to Molded Models
      for Simulated Repair of Pediatric Atrioventricular Valves.
AB  - Mastering the technical skills required to perform pediatric cardiac valve
      surgery is challenging in part due to limited opportunity for practice.
      Transformation of 3D echocardiographic (echo) images of congenitally abnormal
      heart valves to realistic physical models could allow patient-specific simulation
      of surgical valve repair. We compared materials, processes, and costs for 3D
      printing and molding of patient-specific models for visualization and surgical
      simulation of congenitally abnormal heart valves. Pediatric atrioventricular
      valves (mitral, tricuspid, and common atrioventricular valve) were modeled from
      transthoracic 3D echo images using semi-automated methods implemented as custom
      modules in 3D Slicer. Valve models were then both 3D printed in soft materials
      and molded in silicone using 3D printed "negative" molds. Using pre-defined
      assessment criteria, valve models were evaluated by congenital cardiac surgeons
      to determine suitability for simulation. Surgeon assessment indicated that the
      molded valves had superior material properties for the purposes of simulation
      compared to directly printed valves (p < 0.01). Patient-specific, 3D echo-derived
      molded valves are a step toward realistic simulation of complex valve repairs but
      require more time and labor to create than directly printed models. Patient
      specific simulation of valve repair in children using such models may be useful
      for surgical training and simulation of complex congenital cases.

PMID- 29181796
TI  - Risk Factors for an Elevated Ventricular End-Diastolic Pressure Prior to the
      Fontan Operation.
AB  - Systemic ventricular end-diastolic pressure (SVEDP) is an important determinant
      of pulmonary artery pressure in those with a Fontan circulation. Predictors of an
      elevated SVEDP have been incompletely identified in this population. All who
      underwent the Fontan operation at our center between 1/2009 and 12/2013 were
      retrospectively identified. SVEDP at the pre-Fontan catheterization and other
      patient variables were extracted. We identified 61 patients. Pre-Fontan SVEDP was
      positively associated with systemic ventricular systolic pressure (beta = 0.4, p
      = 0.004), aortic systolic pressure (beta = 0.3, p = 0.007), aortic mean pressure
      (beta = 0.3, p = 0.02), and decreased ventricular systolic function (p = 0.03).
      Compared to those with pre-Fontan SVEDP <= 7 mmHg, patients with SVEDP > 7 mmHg
      had higher average ventricular systolic pressure (85.0 +/- 7.5 vs. 78.7 +/- 8.3
      mmHg, p = 0.003), higher average descending aorta mean pressure (62.4 +/- 4.9 vs.
      58.6 +/- 8.1 mmHg, p = 0.03), and a higher incidence of decreased ventricular
      systolic function (36 vs. 15%, p = 0.07). For those with a systemic right
      ventricle, the SVEDP decreased significantly from the pre-Stage 2 to pre-Fontan
      measurements (8.7 +/- 2.6 vs. 7.3 +/- 2.0 mmHg, p = 0.02), but not for those with
      a systemic left ventricle (7.8 +/- 2.0 vs. 7.2 +/- 1.8 mmHg, p = 0.3). At pre
      Fontan catheterization, decreased ventricular systolic function and markers of
      systemic afterload were positively associated with the SVEDP. SVEDP decreased
      significantly after Stage 2 for those with a systemic right ventricle, but not
      for those with a systemic left ventricle; the systemic right ventricle may be
      particularly vulnerable to pre-Stage 2 volume loading.

PMID- 29181797
TI  - Incidence of Persistent Left Superior Vena Cava in the Normal Population and in
      Patients with Congenital Heart Diseases Detected Using Echocardiography.
AB  - Reports on the incidence of persistent left superior vena cava (PLSVC) in the
      normal population are limited to studies involving pacemaker implantation
      candidates and cadavers. The incidence in patients with congenital heart diseases
      (CHDs) is estimated to be higher than that in the normal population; however, the
      details are unclear. To investigate the incidence of PLSVC in the normal
      population and in patients with CHDs, subjects were examined prospectively using
      echocardiography. Normal subjects consisted of 2841 successive neonates without
      intra-cardiac or congenital anomalies born in Gifu Prefectural General Medical
      Center. Additionally, 1920 patients with CHDs were evaluated. The incidence of
      PLSVC in normal neonates was 0.21% (95% confidence interval 0.042-0.38%). A high
      incidence (more than 7.0 times the incidence in normal subjects) was observed in
      all CHD patients. The high incidence group included coarctation of the aorta
      (CoA) (23.7%) and double outlet right ventricle (DORV) patients (24.6%). The
      second group consisted of CHD patients with ventricular septal defect (VSD), with
      an incidence ranging from 5.1 to 6.1%. The low incidence group comprised patients
      with other CHDs, with an incidence between 1.5 and 3.1%. The incidence of PLSVC
      in trisomy 21 and atrial septal defect patients was significantly higher than
      that in normal neonates. The incidence of PLSVC in the normal population and in
      patients with CHDs was systematically evaluated for the first time. The incidence
      in CHD patients appeared to be positively influenced by the type of CHD,
      particularly by DORV, CoA, and VSD.

PMID- 29181798
TI  - Low Peak dP/dt in the Descending Aorta in Patients After Successful Aortic Arch
      Repair.
AB  - One of the most important problems in patients with aortic coarctation or
      interruption of the aortic arch after successful aortic arch repair is developing
      cardiovascular disease in the future. It has been reported that the repaired site
      is stiff and generates a new pressure wave reflection, which could lead to
      cardiovascular disease. The purpose of this study was to clarify the influence of
      the repaired portion's stiffness on the pressure waveform in patients. Fifteen
      patients (age: 7.4 +/- 3.2 years) who had successful aortic arch repair were
      enrolled. Their peak dP/dt in the ascending aorta (AAo) and the descending aorta
      (DAo) were compared with those of age-matched controls with a normal aortic arch.
      The ascending and descending aortic systolic blood pressures in aortic arch
      repair patients were higher than those in age-matched controls (AAo: 103.1 +/-
      13.3 vs. 91.9 +/- 9.2 mmHg, p = 0.012 and DAo: 108.7 +/- 16.4 vs. 96.5 +/- 9.9
      mmHg, p = 0.020). Although no difference existed in the peak dP/dt in the AAo
      between the aortic arch repair patients and the controls (572.1 +/- 100.1 vs.
      543.3 +/- 110.2 mmHg/s, p = 0.460), the peak dP/dt in the DAo in the aortic arch
      repair patients was significantly lower than that in the controls (489.3 +/- 75.2
      vs. 579.4 +/- 106.0 mmHg/s, p = 0.013). The peak dP/dt in the DAo in aortic arch
      repair patients is low. The stiff repaired site may attenuate pulsation.

PMID- 29181799
TI  - Modeling blood flow around a thrombus using a hybrid particle-continuum approach.
AB  - A hybrid, multiscale, particle-continuum numerical method is developed for
      resolving the interaction of a realistic thrombus geometry with unsteady
      hemodynamics typically occurring within large arteries. The method is based on a
      discrete particle/element description of the thrombus, coupled to blood flow
      using a fictitious domain finite element method. The efficacy of the discrete
      element approach in representing thrombi with arbitrary aggregate morphology and
      microstructure is demonstrated. The various features of the method are
      illustrated using a series of numerical experiments with a model system
      consisting of an occlusion embedded in a channel. The results from these
      numerical experiments establish that this approach can resolve the complex
      macroscale flow structures emanating from unsteady hemodynamics interacting with
      a thrombus. Simultaneously, it can also resolve micromechanical features, and
      microscale intra-thrombus flow and perfusion. Using a staggering algorithm, the
      method can further capture hemodynamics around time-varying thrombus manifolds.
      This is established using a numerical simulation of lysis of an idealized clot.
      The hybrid particle-continuum description of thrombus-hemodynamics interaction
      mechanics, and the unified treatment of macroscale as well as microscale flow and
      transport, renders significant advantages to the proposed method in enabling
      further investigations of physiological interest in thrombosis within patient
      specific settings.

PMID- 29181800
TI  - Inoculation density is affecting growth conditions of Listeria monocytogenes on
      fresh cut lettuce.
AB  - Listeria monocytogenes is a particular risk for the ready-to-eat food sector
      because of its ability to grow in various environmental conditions. In the
      literature, growth and survival of L. monocytogenes on food is tested using
      inoculation densities ranging from less than 102 to over 105 CFU g-1. Inoculation
      densities on food have been rarely tested as a factor for growth. In this study,
      inoculation densities from 102 to 105 of L. monocytogenes were tested on iceberg
      lettuce (Lactuca sativa) in modified atmospheres and air in model packages at 4
      and 8  degrees C to identify any potential inoculation density effects. On days
      0, 2, 5 and 7, L. monocytogenes was extracted from the lettuce surface and
      enumerated via selective media. The resulting growth curves identified a
      significant inoculation density effect at 4 and 8  degrees C with significantly
      higher amounts of growth (1-2 logs) when lettuce was inoculated at 102 CFU g-1 as
      opposed to 104 and 105 CFU g-1. In contrast, the use of different atmospheres had
      limited influence on growth of L. monocytogenes. In conclusion, greater emphasis
      on inoculation density of L. monocytogenes should be taken in inoculation
      experiments when confirmation of growth or the efficacies of growth inhibiting
      treatments are tested on ready-to-eat food such as lettuce.

PMID- 29181801
TI  - Cross-Cultural Validation of the Korean Version of the Chalder Fatigue Scale.
AB  - PURPOSE: University students are vulnerable to fatigue. If not adequately dealt
      with, fatigue might develop into various health problems and negatively affect
      quality of life (QOL). The present study examined psychometric properties of the
      Korean version of the Chalder Fatigue Scale (K-CFQ) in university students.
      METHOD: Data were obtained from two samples of undergraduate students in Korea.
      The first dataset (N = 557) was collected in a cross-sectional survey in 2015 and
      the second dataset (N = 338) from a longitudinal survey with three time points
      over a semester period in 2016. Participants completed measures of fatigue, QOL,
      depression, anxiety, and sleep quality. RESULTS: Three-factor model (physical
      fatigue, low energy, and mental fatigue) rather than the original two-factor
      model (physical and mental fatigue) provided a better goodness of fit indices to
      the data. Internal consistency of the K-CFQ was satisfactory, with Cronbach's
      alpha value of 0.88 for the total scale and those of subscales ranging from 0.73
      to 0.87. Its convergent validity was supported by its significant association
      with anxiety, depression, sleep quality, and QOL. Significant association between
      T1 K-CFQ with physical QOL at T2 and T3 supported its predictive validity. Its
      known-group validity was proven with higher K-CFQ scores observed in the
      participants with depression and those with poor sleep quality. CONCLUSIONS:
      Current results suggest that K-CFQ is a valid and reliable measure of fatigue,
      and a better model fit of the three-factor structure of the K-CFQ implies
      potential cross-cultural differences in the dimensionality of fatigue.

PMID- 29181802
TI  - Study and Understanding Behavior of Alginate-Inulin Synbiotics Beads for
      Protection and Delivery of Antimicrobial-Producing Probiotics in Colonic
      Simulated Conditions.
AB  - According to the World Health Organization (WHO), using antibiotics as growth
      promoters for livestock-particularly swine-is the principal cause of antibiotic
      resistance. It is therefore clear that finding an alternative to antibiotics
      becomes an emergency. Hundreds of recent studies have appointed probiotics as
      potential candidates to replace or to be used in combination with antibiotics.
      However, bringing probiotics alive to the colon-their site of action-remains a
      big challenge because of different physiological barriers encountered in proximal
      gastrointestinal tract (GIT) such as acidic pH and bile salts that may affect the
      viability of probiotic cultures. To overcome this problem, in previous studies,
      we developed and characterize a synbiotic formula consisting of beads of a
      mixture of alginate and inulin. Three potential probiotics strains namely
      Pediococcus acidilactici UL5 (UL5), Lactobacillus reuteri (LR), and Lactobacillus
      salivarius (LS) were encapsulated to study their release and the behavior of this
      synbiotic formula throughout the GIT using in vitro models. The survival and the
      release of bacteria from beads were studied by specific PMA-qPCR counting. The
      microscopic aspects of the beads were studied using scanning electron microscopy
      (SEM). Moreover, the microbial dynamics inside beads were studied by fluorescence
      microscopy using the live/dead test. Our results have shown that the beads
      containing 5% inulin were the most stable in the stomach and throughout the small
      intestine. However, beads were completely degraded in approximately 3 h of
      incubation in the fermented medium that mimic the colon. These results were
      confirmed by SEM and fluorescence microscopy images. Therefore, it can be stated
      that the AI5 formulation well protected the bacteria in the upper part of the
      digestive tract and allowed their controlled release in the colon.

PMID- 29181803
TI  - Functional Characterization of Probiotic Potential of Novel Pigmented Bacterial
      Strains for Aquaculture Applications.
AB  - The bioprospecting proficient of novel pigmented probiotic strains with respect
      to aquaculture industry was unexplored hitherto. In this study, we investigated
      the probiotic potential of novel pigmented bacterial strains isolated from the
      indigenous soil sediments in their vicinal habitats, which were screened for
      their antimicrobial activity against aquatic pathogens using agar well diffusion
      assay. The strains namely Exiguobacterium acetylicum (S01), Aeromonas veronii
      (V03), and Chryseobacterium joostei (V04) were phenotypically identified and
      confirmed by 16S rRNA gene sequence analysis. Further characterization revealed
      that strains S01 and V03 survive relatively in lower pH and higher bile salt
      concentrations and possess good adherence ability and broad-spectrum antibiotic
      susceptibility. The isolate S01 exhibited the higher adhesion ability to
      hydrocarbons (82%) and mannose-specific adhesion (msa) gene expression.
      Additionally, the probiotic effects were evaluated in Artemia nauplii fed with
      algae supplemented with S01, V03, and V04 strains (2.7 * 107 cfu/mL) for 3 days
      under axenic environment. We observed a significant increase (p < 0.05) in the
      survival rate of Artemia nauplii treated with S01 (83 +/- 5%) and V03 (55 +/-
      5%), whereas the survival rate was only 30 +/- 0% in the untreated group.
      Moreover, the individual length (IL) was increased in treated group S01 (156.7 +/
      2.2 MUm), V03 (146.1 +/- 3.4 MUm), and V04 (134.4 +/- 2.5 MUm) compared with
      untreated group (116.0 +/- 4.8 MUm). Our results revealed that E. acetylicum S01
      exhibits desirable functional probiotic attributes compared to A. veronii and C.
      joostei and it would be a promising probiotic strain, which can be efficiently
      used in the aquaculture applications.

PMID- 29181804
TI  - Vigorous intensity aerobic interval exercise in bladder cancer patients prior to
      radical cystectomy: a feasibility randomised controlled trial.
AB  - PURPOSE: Strategies to improve pre-operative cardiopulmonary fitness could
      positively impact recovery after surgery. This study investigated the feasibility
      of vigorous intensity aerobic interval exercise in bladder cancer patients prior
      to radical cystectomy (RC). METHODS: A total of 60 patients were randomised (1:1)
      to exercise or control following a cardiopulmonary exercise test (CPET). The
      exercise group was offered twice-weekly pre-operative supervised vigorous
      intensity aerobic interval exercise in addition to standard treatment. The
      controls received standard treatment only. A repeat CPET was undertaken before
      surgery and post-operative recovery outcomes were recorded. RESULTS: Over half of
      the 112 eligible patients approached in the clinic were recruited to the study
      (53.5%), with recruited patients attending a median of 8 (range 1-10) exercise
      sessions over a pre-operative period of 3-6 weeks. Improvements in peak values of
      oxygen pulse (P = 0.001), minute ventilation (P = 0.002) and power output (P <
      0.001) were observed at the follow-up CPET in the exercise group versus controls
      and there were no adverse events. Although this feasibility study was not powered
      to detect changes in post-operative recovery outcomes, there were marginal (non
      significant) differences in favour of the exercise group in post-operative
      Clavien-Dindo score and need for high dependency unit inotropic support.
      CONCLUSIONS: Bladder cancer patients respond well to pre-surgical aerobic
      interval exercise, and the improvements in cardiopulmonary fitness variables
      could have important implications for post-operative recuperation after RC. These
      findings provide a strong foundation for an adequately powered randomised
      controlled trial.

PMID- 29181805
TI  - Understanding Power Anomalies in Mediation Analysis.
AB  - Previous studies have found some puzzling power anomalies related to testing the
      indirect effect of a mediator. The power for the indirect effect stagnates and
      even declines as the size of the indirect effect increases. Furthermore, the
      power for the indirect effect can be much higher than the power for the total
      effect in a model where there is no direct effect and therefore the indirect
      effect is of the same magnitude as the total effect. In the presence of direct
      effect, the power for the indirect effect is often much higher than the power for
      the direct effect even when these two effects are of the same magnitude. In this
      study, the limiting distributions of related statistics and their non
      centralities are derived. Computer simulations are conducted to demonstrate their
      validity. These theoretical results are used to explain the observed anomalies.

PMID- 29181806
TI  - "Coil mainly" policy in management of intracranial ACoA aneurysms: single-centre
      experience with the systematic review of literature and meta-analysis.
AB  - Endovascular techniques are still expanding in their capability by introducing
      novel technologies. Nevertheless, anterior communicating artery (ACoA) remains
      the region with high propensity for aneurysm (AN) re-growth after endovascular
      intervention. The purpose of this study is to highlight the ongoing importance
      for microsurgical treatment. The authors conducted a single-institution
      retrospective study of ACoA AN treatment between January 2000 and December 2016
      maintaining "coil mainly" policy. The results are supplied with a systematic
      review of the literature. A total of n = 398 ACoA ANs were treated in n = 398
      consecutive patients (207 females, 191 males). Microsurgical treatment was
      performed for 79 AN patients (54 ruptured, 25 unruptured), and 319 AN patients
      (250 ruptured, 69 unruptured) underwent coiling procedure. Treatment-related
      morbidity and mortality (MM) for unruptured ANs was 0% in the microsurgical and
      1.5% in the endovascular group (p = 1.000). The percentage of patients with none
      or minor permanent deficits after subarachnoid hemorrhage was 74% in the
      microsurgical and 70% in the endovascular group (p = 0.693). The re-treatment
      rate was 3.8% in microsurgical group and 9.2% in endovascular group (p = 0.883).
      A literature review identified 39 studies concerning ACoA AN treatment. Clinical
      results of both modalities were comparable, with microsurgery being superior
      regarding radiological outcomes. This study demonstrates that both treatment
      techniques bring comparable clinical benefit to the patient. Microsurgery seemed
      superior regarding radiological outcomes. The decision about the treatment
      strategy should be made by a multi-disciplinary team consisting of specialists
      from both teams, bearing in mind the higher occlusion rate and longevity of the
      surgical treatment.

PMID- 29181809
TI  - [Trends in incidence of lung cancer according to histological subtype among men
      and women in Germany : Analysis of cancer registry data with the application of
      multiple imputation techniques].
AB  - BACKGROUND: Lung cancer can be described by histological subtype, of which small
      cell, squamous cell and adenocarcinoma are the most common. International data
      show that adenocarcinoma is becoming the dominant histological subtype of lung
      cancer although the relative risk due to smoking has been found to be smaller
      than that for other histological subtypes. OBJECTIVE: The aim of the analysis was
      to describe the time trends in incidence of lung cancer among women and men in
      Germany according to histological subtype. MATERIALS AND METHODS: All lung cancer
      cases (ICD-10 C33-C34) newly diagnosed between 2003 and 2012 and collected by the
      epidemiologic cancer registries of the German federal states with average
      completeness of registration of at least 90% were considered and grouped into
      histologic subtypes. If data on tumor histology were not microscopically verified
      or unspecific, multiple imputation techniques were applied to estimate the
      histologic subtype. RESULTS: Among women age-standardized lung cancer rates
      increased considerably between 2003 and 2012 (annual percent change APC = 2.7%),
      mostly driven by a rising adenocarcinoma incidence (APC = 4.7%). Among men
      overall lung cancer rates decreased during the same time (APC = -1.7%). Still, a
      slight increase in adenocarcinoma incidence was also observed in men (APC =
      1.0%). CONCLUSION: The rising incidence of adenocarcinoma of the lung is
      alarming. The cancer registry data do not allow risk factor analysis. In the
      international discussion, the introduction of filter cigarettes as well as the
      changing composition of cigarettes has been hypothesized as being responsible.
      Further epidemiologic studies are strongly needed.

PMID- 29181808
TI  - Socially Constructed Hierarchies of Impairments: The Case of Australian and Irish
      Workers' Access to Compensation for Injuries.
AB  - OBJECTIVES: Socially constructed hierarchies of impairment complicate the general
      disadvantage experienced by workers with disabilities. Workers with a range of
      abilities categorized as a "disability" are likely to experience less favourable
      treatment at work and have their rights to work discounted by laws and
      institutions, as compared to workers without disabilities. Value judgments in
      workplace culture and local law mean that the extent of disadvantage experienced
      by workers with disabilities additionally will depend upon the type of impairment
      they have. Rather than focusing upon the extent and severity of the impairment
      and how society turns an impairment into a recognized disability, this article
      aims to critically analyse the social hierarchy of physical versus mental
      impairment. METHODS: Using legal doctrinal research methods, this paper analysis
      how Australian and Irish workers' compensation and negligence laws regard workers
      with mental injuries and impairments as less deserving of compensation and
      protection than like workers who have physical and sensory injuries or
      impairments. RESULTS: This research finds that workers who acquire and manifest
      mental injuries and impairments at work are less able to obtain compensation and
      protection than workers who have developed physical and sensory injuries of equal
      or lesser severity. Organizational cultures and governmental laws and policies
      that treat workers less favourably because they have mental injuries and
      impairments perpetuates unfair and artificial hierarchies of disability
      attributes. CONCLUSIONS: We conclude that these "sanist" attitudes undermine
      equal access to compensation for workplace injury as prohibited by the United
      Nations Convention on the Rights of Persons with Disabilities.

PMID- 29181807
TI  - Pharmacogenomic Biomarkers for Improved Drug Therapy-Recent Progress and Future
      Developments.
AB  - Much of the inter-individual variability in drug efficacy and risk of adverse
      reactions is due to polymorphisms in genes encoding proteins involved in drug
      pharmacokinetics and pharmacodynamics or immunological responses. Pharmacogenetic
      research has identified a multitude of gene-drug response associations, which
      have resulted in genetically guided treatment and dosing decisions to yield a
      higher success rate of pharmacological treatment. The rapid technological
      developments for genetic analyses reveal that the number of genetic variants with
      importance for drug action is much higher than previously thought and that a true
      personalized prediction of drug response requires attention to millions of rare
      mutations. Here, we review the evolutionary background of genetic polymorphisms
      in drug-metabolizing enzymes, provide some important examples of current use of
      pharmacogenomic biomarkers, and give an update of germline and somatic genome
      biomarkers that are in use in drug development and clinical practice. We also
      discuss the current technology development with emphasis on complex genetic loci,
      review current initiatives for validation of pharmacogenomic biomarkers, and
      present scenarios for the future taking rare genetic variants into account for a
      true personalized genetically guided drug prescription. We conclude that
      pharmacogenomic information for patient stratification is of value to tailor
      optimized treatment regimens particularly in oncology. However, the routine use
      of pharmacogenomic biomarkers in clinical practice in other therapeutic areas is
      currently sparse and the prospects of its future implementation are being
      scrutinized by different international consortia.

PMID- 29181811
TI  - Temperature Dependence of Arn+ Cluster Backscattering from Polymer Surfaces: a
      New Method to Determine the Surface Glass Transition Temperature.
AB  - In this work, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used
      to study the intensity variations of the backscattered Arn+ clusters as a
      function of temperature for several amorphous polymer surfaces (polyolefins,
      polystyrene, and polymethyl methacrylate). For all these investigated polymers,
      our results show a transition of the ratio Ar2+/(Ar2+ + Ar3+) when the
      temperature is scanned from -120  degrees C to +125  degrees C (the exact limits
      depend on the studied polymer). This transition generally spans over a few tens
      of degrees and the temperature of the inflection point of each curve is always
      lower than the bulk glass transition temperature (Tg) reported for the considered
      polymer. Due to the surface sensitivity of the cluster backscattering process
      (several nanometers), the presented analysis could provide a new method to
      specifically evaluate a surface transition temperature of polymers, with the same
      lateral resolution as the gas cluster beam. Graphical abstract ?.

PMID- 29181810
TI  - Imaging findings in congenital Zika virus infection syndrome: an update.
AB  - BACKGROUND: Zika virus (ZIKV) is a neurotropic and neurotoxic RNA Flavivirus
      prompt to cause severe fetal brain dysmorphisms during pregnancy, a period of
      rapid and critical central nervous system development. A wide range of clinico
      radiological findings of congenital ZIKV infections were reported in the
      literature, such as microcephaly, overlapping sutures, cortical migrational and
      corpus callosum abnormalities, intracranial calcifications, ventriculomegaly,
      brain stem and cerebellar malformations, spinal cord involvement, and joint
      contractures. ZIKV is also related to other severe neurological manifestations in
      grown-up individuals such as Guillain-Barre syndrome and encephalomyelitis.
      PURPOSE: Our purpose is to review the radiological central nervous system
      abnormalities of congenital ZIKV infection syndrome on different imaging
      modalities.

PMID- 29181812
TI  - MALDI-TOF-MS with PLS Modeling Enables Strain Typing of the Bacterial Plant
      Pathogen Xanthomonas axonopodis.
AB  - Matrix-assisted desorption/ionization time of flight mass spectrometry (MALDI-TOF
      MS) is a fast and effective tool for microbial species identification. However,
      current approaches are limited to species-level identification even when genetic
      differences are known. Here, we present a novel workflow that applies the
      statistical method of partial least squares discriminant analysis (PLS-DA) to
      MALDI-TOF-MS protein fingerprint data of Xanthomonas axonopodis, an important
      bacterial plant pathogen of fruit and vegetable crops. Mass spectra of 32 X.
      axonopodis strains were used to create a mass spectral library and PLS-DA was
      employed to model the closely related strains. A robust workflow was designed to
      optimize the PLS-DA model by assessing the model performance over a range of
      signal-to-noise ratios (s/n) and mass filter (MF) thresholds. The optimized
      parameters were observed to be s/n = 3 and MF = 0.7. The model correctly
      classified 83% of spectra withheld from the model as a test set. A new decision
      rule was developed, termed the rolled-up Maximum Decision Rule (ruMDR), and this
      method improved identification rates to 92%. These results demonstrate that MALDI
      TOF-MS protein fingerprints of bacterial isolates can be utilized to enable
      identification at the strain level. Furthermore, the open-source framework of
      this workflow allows for broad implementation across various instrument platforms
      as well as integration with alternative modeling and classification algorithms.
      Graphical abstract ?.

PMID- 29181813
TI  - Probe-Substrate Distance Control in Desorption Electrospray Ionization.
AB  - We introduce probe-substrate distance (Dps)-control to desorption electrospray
      ionization (DESI) and report a systematic investigation of key experimental
      parameters. Examination of voltage, flow rate, and nebulizing gas pressure
      suggests as Dps decreases, the distance-dependent spray current increases, until
      a critical point. At the critical point the relationship inverts, and the spray
      current decreases as the probe moves closer to the surface due to constriction of
      solution flow by the nebulizing gas. Dps control was used to explore the use of
      spray current as a signal for feedback positioning, while mass spectrometry
      imaging was performed simultaneously. Further development of this technique is
      expected to find application in study of structure-function relationships for
      clinical diagnostics, biological investigation, and materials characterization.
      Graphical abstract ?.

PMID- 29181814
TI  - A high working memory load prior to memory retrieval reduces craving in non
      treatment seeking problem drinkers.
AB  - BACKGROUND: Reconsolidation-based interventions have been suggested to be a
      promising treatment strategy for substance use disorders. In this study, we aimed
      to investigate the effectiveness of a working memory intervention to interfere
      with the reconsolidation of alcohol-related memories in a sample of non-treatment
      seeking heavy drinkers. METHODS: Participants were randomized to one of the two
      conditions that underwent a 3-day intervention: in the experimental condition, a
      30-min working memory training was performed immediately after a 15-min memory
      retrieval session (i.e., within the memory reconsolidation time-window), whereas
      in the control condition, the working memory training was performed prior to a
      memory retrieval session. RESULTS: In contrast to our original hypothesis, a high
      working memory load after memory retrieval did not interfere with the
      reconsolidation of those memories while a high working memory load prior to
      memory retrieval (the original control condition) strongly reduced retrieval
      induced craving and craving for alcohol at follow-up. CONCLUSION: Whereas the
      neurocognitive mechanism behind this effect needs to be further investigated, the
      current findings suggest that, if replicated, working memory training prior to
      addiction-related memory retrieval has the potential to become an effective
      (adjunctive) intervention in the treatment of substance use disorders.

PMID- 29181815
TI  - Effects of adolescent alcohol exposure on stress-induced reward deficits, brain
      CRF, monoamines and glutamate in adult rats.
AB  - BACKGROUND: Adolescent alcohol exposure may increase depression vulnerability in
      adulthood by increasing the anhedonic response to stress. METHODS: Male Wistar
      rats (postnatal days 28-53) were exposed to binge-like adolescent intermittent
      ethanol (AIE) or water. In adulthood, rats were exposed to social defeat,
      consisting of daily confrontations with an aggressive conspecific, followed by
      testing of brain reward function in a discrete-trial current-intensity
      intracranial self-stimulation procedure for 10 consecutive days. Neurochemistry
      and corticotropin-releasing factor (CRF) and CRF receptor 1 (CRFR1) mRNA levels
      were assessed in corticolimbic brain areas on day 11 of social defeat stress.
      RESULTS: Social defeat elevated reward thresholds in both AIE- and water-exposed
      rats indicating stress-induced anhedonia. However, AIE-exposed rats were more
      likely to show threshold elevations after repeated stress compared to water
      exposed rats. AIE exposure decreased CRF mRNA levels in the nucleus accumbens and
      increased CRFR1 mRNA levels in the prefrontal cortex, while stress increased CRF
      mRNA levels in the central amygdala. In the caudate putamen, AIE exposure
      decreased dopamine turnover, while stress increased glutamate and serotonin
      metabolism and turnover. CONCLUSIONS: These results demonstrate increased risk of
      repeated stress-induced anhedonia after AIE exposure, an effect that may be due
      to alterations in brain CRF and dopamine systems. These results suggest that the
      increased rates of depression reported in people with a history of adolescent
      alcohol exposure may be related to alterations in brain reward and stress systems
      that may contribute to increased stress-induced anhedonia.

PMID- 29181818
TI  - Correction for Partial Volume Effect Is a Must, Not a Luxury, to Fully Exploit
      the Potential of Quantitative PET Imaging in Clinical Oncology.
AB  - The partial volume effect (PVE) is considered as one of the major degrading
      factors impacting image quality and hampering the accuracy of quantitative PET
      imaging in clinical oncology. This effect is the consequence of the limited
      spatial resolution of whole-body PET scanners, which results in blurring of the
      generated images by the scanner's response function. A number of strategies have
      been devised to deal with partial volume effect. However, the lack of consensus
      on the clinical relevance of partial volume correction and the most appropriate
      technique to be used in the context of clinical oncology limited their
      application in clinical setting. This issue is debated in this commentary.

PMID- 29181816
TI  - Nicotine-induced activation of caudate and anterior cingulate cortex in response
      to errors in schizophrenia.
AB  - BACKGROUND: Nicotine improves attention and processing speed in individuals with
      schizophrenia. Few studies have investigated the effects of nicotine on cognitive
      control. Prior functional magnetic resonance imaging (fMRI) research demonstrates
      blunted activation of dorsal anterior cingulate cortex (dACC) and rostral
      anterior cingulate cortex (rACC) in response to error and decreased post-error
      slowing in schizophrenia. METHODS: Participants with schizophrenia (n = 13) and
      healthy controls (n = 12) participated in a randomized, placebo-controlled,
      crossover study of the effects of transdermal nicotine on cognitive control. For
      each drug condition, participants underwent fMRI while performing the stop signal
      task where participants attempt to inhibit prepotent responses to "go (motor
      activation)" signals when an occasional "stop (motor inhibition)" signal appears.
      Error processing was evaluated by comparing "stop error" trials (failed response
      inhibition) to "go" trials. Resting-state fMRI data were collected prior to the
      task. RESULTS: Participants with schizophrenia had increased nicotine-induced
      activation of right caudate in response to errors compared to controls (DRUG *
      GROUP effect: p corrected < 0.05). Both groups had significant nicotine-induced
      activation of dACC and rACC in response to errors. Using right caudate activation
      to errors as a seed for resting-state functional connectivity analysis, relative
      to controls, participants with schizophrenia had significantly decreased
      connectivity between the right caudate and dACC/bilateral dorsolateral prefrontal
      cortices. CONCLUSIONS: In sum, we replicated prior findings of decreased post
      error slowing in schizophrenia and found that nicotine was associated with more
      adaptive (i.e., increased) post-error reaction time (RT). This proof-of-concept
      pilot study suggests a role for nicotinic agents in targeting cognitive control
      deficits in schizophrenia.

PMID- 29181817
TI  - Health economic evaluation of rivaroxaban in elective cardioversion of atrial
      fibrillation.
AB  - BACKGROUND: Electrical cardioversion (ECV) is a procedure in which a direct
      current electric shock is used to quickly and effectively restore the normal
      sinus rhythm. Appropriate anticoagulation reduces the risk of embolic events
      during and after ECV. The aim of this study was to estimate the cost
      effectiveness of rivaroxaban compared with vitamin K oral antagonists (VKAs) in
      patients with atrial fibrillation undergoing elective ECV in the Netherlands.
      METHODS AND RESULTS: A static transmission model over a 1-year time horizon was
      developed to compare rivaroxaban with VKAs in terms of clinical outcomes, health
      effects (quality-adjusted life years; QALYs), and costs. Cost-effectiveness was
      assessed from a societal and health care payer perspective at a willingness-to
      pay level of ?20,000 per QALY gained. The use of rivaroxaban as an anticoagulant
      in patients with atrial fibrillation scheduled for ECV would lead to a health
      gain of 0.23 QALYs per patient and would cost ?1.83 per patient from the societal
      perspective, resulting in an incremental cost-effectiveness ratio of ?7.92 per
      QALY gained. The probability of rivaroxaban being cost-saving compared with VKAs
      was 49.6% from this perspective. From the health care payer perspective, the
      incremental cost would be ?509 per patient with a health gain of 0.23 QALYs per
      patient, resulting in an incremental cost-effectiveness ratio of ?2198 per QALY
      gained. CONCLUSIONS: The use of rivaroxaban in elective ECV is a cost-effective
      alternative to the use of VKAs. Rivaroxaban has a 50% probability of being cost
      saving compared with VKAs and would increase a patient's quality of life when non
      health care costs such as productivity loss and informal care costs are taken
      into account.

PMID- 29181819
TI  - Translating Molecular Imaging of the Vulnerable Plaque-a Vulnerable Project?

PMID- 29181820
TI  - Role of Trace Elements, Oxidative Stress and Immune System: a Triad in Premature
      Ovarian Failure.
AB  - The risk of premature ovarian failure (POF) increases in association with
      alteration in immunological parameters and oxidative stress (OS). Adequate intake
      of trace elements is required for antioxidant property and immune defense
      mechanism. The aim of this study was to explore the involvement of trace
      elements, OS, and immunological parameters in POF. This was a cross-sectional,
      case-control study, involving 65 participants divided into the POF (n = 35) and
      control (n = 30) groups. Serum levels of Se, Zn, and Cu were determined along
      with hormonal, OS, and immunological markers. POF group had significantly lower
      levels of Zn, Cu, Se, and Zn:Cu ratio. However, Se:Cu ratio was not significant
      between the groups. FSH and LH levels were negatively correlated with Zn and Cu
      levels and positively correlated with Se levels. Estrogen levels were negatively
      correlated with all the studied trace elements. Inter-element association between
      Zn and Se was significant in POF (r = - 0.39, p = 0.02) compared to control group
      (r = - 0.078, p = 0.65). In all the POF patients, SOD and GPx activities were
      significantly (p < 0.05) lower and MDA level was higher (p > 0.05) than control
      group. B cell marker CD19 was significantly (p < 0.0001) high in POF group. There
      are involvement of trace elements in hormonal regulation and antioxidant defense
      mechanism, which once gets altered leads to high ROS generation and affect
      functions of the immune system. Exaggereative immune system causing higher
      expression of B cell associated markers (CD19) leading to autoimmune condition in
      POF.

PMID- 29181821
TI  - Combination Effects of Organic and Inorganic Chromium on Production Performance,
      Reproductive Response, Immune Status, and Maternal Antibody Transmission in
      Breeder Quails Under Heat Stress.
AB  - This experiment was carried out to investigate the combination effects of organic
      and inorganic chromium (Cr) on egg production, egg quality, reproductive
      response, and immune status of breeder quails and their offspring under heat
      stress. A total of 140 7-week-old Japanese breeder quails (120 females and 20
      males) according to a completely randomized design were used in four treatment
      groups (five replicate and seven birds per each) lasted for 8 weeks. Quails
      exposed to 35  degrees C for 8 h/day for induction of cyclic heat stress
      treatments consisted of diets supplemented with (1) 1 mg CrCl3 per kilogram of
      diet as control (CNT); (2) 1 mg Cr-L-Met per kilogram of diet as organic Cr
      (OCr); (3) 0.5 mg CrCl3 plus 0.5 mg Cr-L-Met per kilogram of diet (ISO); (4) 1 mg
      CrCl3 plus 0.5 mg Cr-L-Met per kilogram of diet (On-top). Productive performance
      and egg quality parameters were determined weekly. Fertility, hatchability, and
      embryonic mortality were measured at the end of experiment. Humoral immunity was
      assessed by primary and secondary antibody titer in sheep red blood cells (SRBC)
      and Newcastle disease (ND) tests. Cell-mediated immunity was assessed by the
      cutaneous basophil hypersensitivity (CBH) test to phytohemagglutinin (PHA) at
      days 20 and 45 of age. White blood cell count and immunoglobulin Y (IgY) content
      in serum and yolk of breeders and in serum and yolk residues of offspring were
      also measured. Results showed that maximum egg production, egg shell thickness,
      and Haugh unit were observed in birds fed ISO and On-top diets (P <= 0.05). The
      highest (P <= 0.05) antibody levels in ND test were observed in birds fed with
      OCr, ISO, and On-top diets. The highest cellular response (P <= 0.05) was in 12 h
      after primary PHA injection and 12 and 24 h after secondary PHA injection in
      birds fed with On-top diets. The highest count of heterophil and (H/L) were
      gained in breeder quails fed with CNT diet, and the lowest of them were reached
      with On-top diet (P <= 0.05). Results showed that the highest IgY level in serum
      of breeder and their offspring and that of yolk suck and egg yolk were observed
      in birds fed with On-top diet (P <= 0.05). These results suggest that extra
      supplemental organic Cr in combination with CrCl3 could lead to higher egg
      production, egg quality, and immune status of breeder quails and their offspring.

PMID- 29181822
TI  - Schisandrin A reverses doxorubicin-resistant human breast cancer cell line by the
      inhibition of P65 and Stat3 phosphorylation.
AB  - BACKGROUND: Multidrug resistance (MDR) in breast cancer therapy occurs
      frequently. Thus, anti-MDR agents from natural products or synthetic compounds
      were tested extensively. We have also explored the reverse effect and mechanism
      of Schisandrin A (Sch A), a natural product, on MCF-7 breast cancer doxorubicin
      (DOX)-resistant subline MCF-7/DOX. METHODS: MTT assay was performed to measure
      the viability of MCF-7 cells to assess the reverse effect of Sch A. Western blot
      analysis was used to study the protein levels. Laser scanning confocal microscopy
      was performed to detect the intercellular DOX and Rhodamine 123 accumulation. The
      qRT-PCR was used to analysis the target gene expression. Dual-luciferase reporter
      assay was performed to test the transcriptional activity of P-glycoprotein (P
      gp). RESULTS: Sch A, at the concentration of 20 uM, showed selective reverse
      effect (better than the positive control, verapamil at 5 uM) on MCF-7/DOX cell
      line but not on BEL-7402/DOX, Hep G2/DOX, and K-562/DOX cells. In addition, Sch A
      enhanced DOX-induced cleavage of Caspase-9 and PARP levels by increasing
      intracellular DOX accumulation and inhibiting P-gp function. Furthermore, Sch A
      selectively suppressed P-gp at gene and protein levels in MCF-7/DOX cells which
      express high level of MDR1 but not MRP1, MRP3, or BCRP. Besides, Sch A showed
      inhibitory effect on P-gp transcriptional activity. Sch A significantly reduced p
      IkappaB-alpha (Ser32) and p-Stat3 (Tyr705) levels which mediate P-gp expression.
      In addition, Stat3 knockdown enhanced the reverse effect of siP65. The combined
      effect of siStat3 and siP65 was better than Sch A single treatment in MCF-7/DOX
      cells. CONCLUSION: Sch A specifically reverses P-gp-mediated DOX resistance in
      MCF-7/DOX cells by blocking P-gp, NF-kappaB, and Stat3 signaling. Inhibition of
      P65 and Stat3 shows potent anti-MDR effect on MCF-7/DOX cells.

PMID- 29181823
TI  - A case of acute kidney injury caused by granulomatous interstitial nephritis
      associated with sarcoidosis.
AB  - Sarcoidosis affects multiple organs including lung, heart and kidney. Sarcoidosis
      causes hypercalcemia, hypergammaglobulinemia, and rarely, granulomatous
      interstitial nephritis, resulting in renal stromal damage. Granulomatous
      interstitial nephritis is characterized as interstitial nephritis with
      noncaseating epithelioid granulomas. Diagnosing granulomatous interstitial
      nephritis before patient's death is challenging; hence, only few cases proven by
      renal biopsy have been reported till date. We present a case of acute kidney
      injury caused by granulomatous interstitial nephritis as a renal manifestation of
      sarcoidosis proven by renal biopsy, which can be confirmed by 18F
      fluorodeoxyglucose positron emission tomography/computed tomography.
      Glucocorticoid therapy was helpful for improving and maintaining her renal
      function over a 6-year period.

PMID- 29181824
TI  - AGEs-RAGE overexpression in a patient with smoking-related idiopathic nodular
      glomerulosclerosis.
AB  - We report a case of smoking-related idiopathic nodular glomerulosclerosis (ING)
      with overexpression of glomerular advanced glycation end products (AGEs) and
      their receptor (RAGE). A 59-year-old Japanese man with nephrotic syndrome, who
      had a smoking history of one pack of cigarettes per day for approximately 40
      years, presented with a 3-year history of urinalysis abnormalities without
      clinical evidence of diabetic mellitus. The patient's leg edema progressively
      worsened over the previous 2 years, and he was admitted to our hospital. Renal
      biopsy showed mesangial expansion with diabetic Kimmelstiel-Wilson-like nodular
      lesions, glomerular basement thickening, and arteriosclerosis. No electron-dense
      deposits, fibrils, or microtubule deposits were seen in the glomeruli on electron
      microscopy. Skin AGE level measured using AGE reader was higher in this case than
      the average level in age-matched Caucasians. In addition, immunohistochemical
      analysis revealed that N-carboxymethyl lysine, one of the major AGEs, and RAGE
      were overexpressed and podocin expression was decreased in the peripheral area of
      the glomerular nodular lesions. These observations suggest that AGEs-RAGE system
      may be activated in smoking-related ING, possibly leading to the progression of
      renal dysfunction.

PMID- 29181825
TI  - A primary hepatic gastrinoma accompanied by hyperplasia of multi-nodular
      Brunner's glands.
AB  - BACKGROUND: Primary hepatic gastrinoma causing severe ulcerogenic syndrome is
      extremely rare. Herein, we report a case of primary hepatic gastrinoma
      accompanied by hyperplasia of multi-nodular Brunner's glands in a patient who
      instead, preoperatively, was suspected of having multiple duodenal gastrinomas
      and hepatic metastasis. CASE PRESENTATION: A 57-year-old woman consulted a clinic
      complaining of melena, intermittent abdominal pain, diarrhea, and vomiting which
      had persisted for about 3 years. Six months before her presentation, she
      underwent segmental resection of the jejunum for acute peritonitis due to the
      spontaneous jejunal perforation. A blood test revealed that her serum
      immunoreactive gastrin (IRG) level was 12,037 pg/mL. Subsequently, she was
      transferred to our hospital. On computed tomography (CT), a hypervascular tumor
      of 23 mm in the segment 5 (S5) region of the liver was visualized. A selective
      arterial secretagogue injection test (SASI test) was performed twice. The first
      SASI test revealed that the hepatic tumor was a gastrinoma, and there was no
      gastrinoma in the duodeno-pancreatic region. Additionally, somatostatin receptor
      scintigraphy only visualized the tumor in the liver. However, the second SASI
      test, which was performed during the administration of a proton pump inhibitor
      and a somatostatin analog (octreotide acetate), revealed that there may have been
      gastrinomas existing not only in the liver but also in the upper part of the
      duodenum or the head of the pancreas. Duodenal endoscopy revealed multiple
      submucosal tumors in the first and the second portion of the duodenum, although a
      pathological examination of biopsied specimens obtained from the duodenal lesions
      was negative for malignant cells. Multiple endocrine neoplasia type 1 (MEN1) was
      excluded from her family history, and serum levels of both intact parathyroid
      hormone (iPTH) and calcium were within normal ranges. An anterior segmentectomy
      of the liver and pancreas-preserving total duodenectomy were performed on
      September 9, 2013. Postoperatively, her serum immunoreactive gastrin level
      decreased to less than 50 pg/mL. Pathological study of the resected specimens
      revealed a gastrinoma in the liver, but no gastrinoma in the duodenum.
      Interestingly, the duodenal submucosal tumor-like lesions were hyperplastic
      Brunner's glands. Postoperatively, she has been well without recurrence of
      hypergastrinemia for 4 years. CONCLUSION: We report a case of primary hepatic
      gastrinoma in a patient who has been cured for 4 years postoperatively. The
      diagnosis was somewhat difficult due to the coexisting, multiple hyperplastic
      Brunner's glands of the duodenum mimicking the submucosal neuroendocrine tumors,
      which might have developed due to long-term hypergastrinemia.

PMID- 29181826
TI  - Speckle tracking imaging in inflammatory heart diseases.
AB  - Accurate diagnosis of acute myocarditis is important for the prognosis and risk
      stratification of these patients. Cardiac magnetic resonance (CMR) has become a
      major modality for diagnosis of myocarditis, but not widely available. In this
      study, we tried to evaluate regional and global longitudinal strain by speckle
      tracking echocardiography in patients with acute inflammatory myocardial diseases
      in correlation with CMR. Patients with suspected acute myocarditis were recruited
      prospectively. Clinical diagnosis was established based on clinical,
      electrocardiographic, laboratory and conventional echocardiographic data. All
      patients underwent CMR and repeat echocardiographic examination within 24 h of
      CMR. Echocardiographic examinations were analyzed offline with speckle tracking
      imaging software. Thirty-two patients with acute perimyocarditis and
      myopericarditis were included. Mean age was 29 +/- 8, 30 males. All patients
      presented with chest pain and an abnormal electrocardiogram, in 28 ST elevation
      was found. Troponin was elevated in 30 and was 0.7 +/- 0.5 ng/ml. Creatine kinase
      was 487 +/- 319 U. LVEF was 56 +/- 5%. Wall motion abnormalities were present in
      postero-lateral (53%), and inferior wall (21%). Delayed enhancement on CMR was
      found in 29 patients. Echocardiographic EF based on speckle tracking imaging
      correlated with CMR calculated EF. There was a positive correlation between the
      amplitude of regional strain and delayed enhancement, r = 0.52. Sensitivity and
      specificity of regional strain for prediction of delayed enhancement was 85 and
      73% respectively. Speckle tracking imaging can help in the diagnosis of acute
      myocarditis when CMR is not readily available. Speckle tracking imaging based EF
      correlates with CMR calculated LVEF and with global strain.

PMID- 29181827
TI  - Reference ranges for three-dimensional feature tracking cardiac magnetic
      resonance: comparison with two-dimensional methodology and relevance of age and
      gender.
AB  - Myocardial deformation is a sensitive marker of sub-clinical myocardial
      dysfunction that carries independent prognostic significance across a broad range
      of cardiovascular diseases. It is now possible to perform 3D feature tracking of
      SSFP cines on cardiac magnetic resonance imaging (FT-CMR). This study provides
      reference ranges for 3D FT-CMR and assesses its reproducibility compared to 2D FT
      CMR. One hundred healthy individuals with 10 men and women in each of 5 age
      deciles from 20 to 70 years, underwent 2D and 3D FT-CMR of left ventricular
      myocardial strain and strain rate using SSFP cines. Good health was defined by
      the absence of hypertension, diabetes, obesity, dyslipidaemia, or any
      cardiovascular, renal, hepatic, haematological and systemic inflammatory disease.
      Normal values for myocardial strain assessed by 3D FT-CMR were consistently lower
      compared with 2D FT-CMR measures [global circumferential strain (GCS) 3D - 17.6
      +/- 2.6% vs. 2D - 20.9 +/- 3.7%, P < 0.005]. Validity of 3D FT-CMR was confirmed
      against other markers of systolic function. The 3D algorithm improved
      reproducibility compared to 2D, with GCS having the best inter-observer agreement
      [intra-class correlation (ICC) 0.88], followed by global radial strain (GRS; ICC
      0.79) and global longitudinal strain (GLS, ICC 0.74). On linear regression
      analyses, increasing age was weakly associated with increased GCS (R2 = 0.15, R =
      0.38), peak systolic strain rate, peak late diastolic strain rate, and lower peak
      early systolic strain rate. 3D FT-CMR offers superior reproducibility compared to
      2D FT-CMR, with circumferential strain and strain rates offering excellent intra-
      and inter-observer variability. Normal range values for myocardial strain
      measurements using 3D FT-CMR are provided.

PMID- 29181828
TI  - Influence of Inhaled Corticosteroids on Bronchial Inflammation and Pulmonary
      Function in Chronic Obstructive Pulmonary Disease with Moderate Obstruction.
AB  - Inflammation in the bronchial respiratory tract and lung parenchyma underlies the
      pathogenesis of chronic obstructive pulmonary disease (COPD). It consists of
      effector cell infiltration, changes in reticular basement membrane (RBM)
      thickness, and the content of inflammatory mediators. The aim of this study was
      to assess the influence of inhaled corticosteroids (ICS) on the number of
      inflammatory cells and RBM thickness in bronchial biopsies, and pulmonary
      function in patients with moderate COPD. Twenty four patients with newly
      diagnosed COPD were included into the study. Pulmonary function tests and fiber
      optic bronchoscopy with bronchial biopsies were performed before and after 12
      month treatment in two groups: ICS- group (LABA plus anticholinergics) and ICS+
      group (LABA plus anticholinergics plus ICS). We found that the addition of
      inhaled corticosteroids to the therapeutic regimen contributed to a reduction of
      RBM thickness, inflammation, and lung hyperinflation. The intensity of bronchial
      inflammatory infiltration had little effect on lung function. In conclusion, RBM
      thickness, an airway wall remodeling element, does not significantly affect the
      degree of airflow limitation.

PMID- 29181829
TI  - Long-term endurance training increases serum cathepsin S levels in healthy female
      subjects.
AB  - BACKGROUND: Circulating cathepsin S (CS) has been associated with a lower risk
      for breast cancer in a large Swedish cohort. Long-term physical activity has been
      shown to have beneficial effects on the development of various cancer subtypes,
      in particular breast and colorectal cancers. The aim of this study was to
      investigate the effect of long-term endurance sport on CS levels in females.
      MATERIAL AND METHODS: Thirty-six of 40 subjects completed the study. Subjects
      were told to increase their activity pensum for 8 months reaching 150 min/week
      moderate or 75 min/week intense exercise. Ergometries were performed at the
      beginning and the end of the study to prove/quantify the performance gain. Blood
      samples were drawn at baseline and every 2 months. Serum CS levels were measured
      by ELISA. To analyse the change and the progression of CS, Wilcoxon rank sum and
      Friedman tests were used. RESULTS: The sportive group (performance gain by >
      4.9%) showed a significant increase of CS levels from 3.32/2.73/4.09 to
      4.00/3.09/5.04 ng/ml (p = 0.008) corresponding to an increase of 20.5%.
      CONCLUSIONS: We could show a significant increase of circulating CS levels in
      healthy female subjects induced by long-term physical activity. CS, occurring in
      the tumour microenvironment, is well-known to promote tumour growth, e.g. by
      ameliorating angiogenesis. However, the role of circulating CS in cancer growth
      is not clear. As physical activity is known as preventive intervention, in
      particular concerning breast and colorectal cancers, and long-term physical
      activity leads to an increase of CS levels in female subjects, circulating CS
      might even be involved in this protective effect. TRIAL REGISTRATION: Clinical
      trial registration: NCT02097199.

PMID- 29181830
TI  - Correction to: MRI and multiple sclerosis-the evolving role of MRI in the
      diagnosis and management of MS: a clinician's perspective.
AB  - The original version of this article unfortunately contained a mistake. The
      presentation of Table 1 was incorrectly captured. The Publisher regrets that it
      introduced errors to Table 1 during the typesetting of the article. The original
      article has been corrected.

PMID- 29181832
TI  - Pluronic-F127 composite film loaded with erythromycin for wound application:
      formulation, physicomechanical and in vitro evaluations.
AB  - Composite film dressings composed of pluronic F127 (PL)-pectin (PC) and pluronic
      (PL) F127-gelatin (GL) were investigated as potential drug delivery system for
      wound healing. Composite films were solvent cast by blending PL with PC or GL in
      different ratios using glycerol (2.5%) as plasticizer. Erythromycin (ER) (0.1%)
      was incorporated in films as model hydrophobic antibiotic. The optimized
      composite films were characterized for physical appearance, morphology,
      mechanical profile, and thermal behavior. In addition, drug release,
      antibacterial activity, and cytocompatibility of the films were investigated to
      assess their potential as drug delivery system. The composite films exhibited
      excellent wound dressing characters in terms of appearance, stability, and
      mechanical profile. Moreover, ER-loaded composite films released ER in controlled
      manner, exhibited antibacterial activity against Staphylococcus aureus, and were
      non-toxic to human skin fibroblast. These findings demonstrate that these
      composite films hold the potential to be formulated as antibacterial wound
      dressing.

PMID- 29181831
TI  - Molecular guidance cues in the development of visual pathway.
AB  - 70%-80% of our sensory input comes from vision. Light hit the retina at the back
      of our eyes and the visual information is relayed into the dorsal lateral
      geniculate nuclei (dLGN) and primary visual cortex (V1) thereafter, constituting
      the image-forming visual circuit. Molecular cues are one of the key factors to
      guide the wiring and refinement of the image-forming visual circuit during pre-
      and post-embryonic stages. Distinct molecular cues are involved in different
      developmental stages and nucleus, suggesting diverse guidance mechanisms. In this
      review, we summarize molecular guidance cues throughout the image-forming visual
      circuit, including chiasm determination, eye-specific segregation and refinement
      in the dLGN, and at last the reciprocal connections between the dLGN and V1.

PMID- 29181833
TI  - Influence of polymeric carrier on the disposition and retention of 20(R)
      ginsenoside-rg3-loaded swellable microparticles in the lung.
AB  - The objective of this study was to investigate the influence of differently
      charged biocompatible polymers, including chitosan (CS), hyaluronic acid (HA),
      and hydroxypropyl cellulose (HPC), on the disposition and retention of 20(R)
      ginsenoside-rg3 (Rg3)-loaded swellable microparticles in the lung. A high
      pressure homogenization method combined with spray drying was used to prepare Rg3
      loaded microparticles. In vitro aerodynamic performance of different
      microparticles was characterized by the Next Generation Impactor (NGI). Retention
      of the swellable microparticles in the rat lung was investigated using
      bronchoalveolar lavage fluid method. Influence of drug loading, polymer molecular
      weight, and polymer charge on the properties of the swellable microparticles was
      investigated. It was found that drug loading had no significant influence on
      experimental mass median aerodynamic diameter (MMADe) and fine particle fraction
      (FPF). Increasing polymer molecular weight caused no remarkable change in MMADe
      value, but the FPF value decreased with the increase of polymer molecular weight.
      At the same molecular weight level, polymer structure and charge had no
      statistical influence on the in vitro aerodynamic properties of the
      microparticles and lung disposition, but it influenced the swelling and
      bioadhesion behavior and therefore lung retention profile. Desirable phagocytosis
      escapement and inhibition of A549 cell proliferation were achieved for the
      developed swellable microparticles. In conclusion, the lung retention of
      swellable microparticles can be adjusted by selecting polymeric carriers with
      different structure and charge.

PMID- 29181834
TI  - Ion-pair formation combined with a penetration enhancer as a dual strategy to
      improve the transdermal delivery of meloxicam.
AB  - The aim of the study was to develop a novel drug-in-adhesive patch for
      transdermal delivery of meloxicam (MLX). The formulation involved a strategy to
      combine a chemical enhancer with an ion-pair agent. Diethylamine (DETA) was
      selected as the counter ion to form the ion-pair agent MLX-DETA. MLX-DETA was
      characterized by nuclear magnetic resonance spectroscopy (NMR) and Fourier
      transform infrared spectroscopy (FTIR). The ion-pair lifetime (T life) of MLX
      DETA was 164.1 MUs. The water solubility of MLX-DETA was increased nearly 9.3
      fold, compared with that of MLX. Oleic acid (OA) was selected as the chemical
      enhancer, and the optimized formulation consisted of 5% (w/w) MLX-DETA, 5% (w/w)
      oleic acid, and DURO-TAK(r) 87-4098 adhesive as the pressure-sensitive adhesive
      matrix. The permeation study in vitro showed that both the counter ion and
      chemical enhancer were effective in improving the skin permeation of MLX. Tissue
      distribution studies demonstrated that higher accumulation of MLX following
      application of the MLX-DETA patch to the skin could be obtained in rats compared
      with the MLX-patch group. In conclusion, to increase the skin absorption and
      obtain a sustained release for the transdermal delivery of MLX, preparation of a
      drug-in-adhesive patch by combining an ion pair (MLX-DETA) with a permeation
      enhancer (OA) is a suitable strategy.

PMID- 29181836
TI  - Strategies for Addressing Cancer Patients' Complaints of Fatigue.
AB  - Cancer-related fatigue is a complex and common symptom for cancer patients. This
      article reviews important topics that oncology practitioners should know to
      better manage fatigue in this patient population. Our discussion includes
      identification and assessment of fatigue severity, as well as screening for
      comorbid conditions that may be contributing to an individual patient's fatigue.
      Finally, we review nonpharmacologic and pharmacologic interventions for the
      treatment of cancer-related fatigue and the associated literature supporting
      their effectiveness.

PMID- 29181835
TI  - Nanoparticles in thermosensitive gel based composite nanosystem for ocular
      diseases.
AB  - The pentablock (PB) copolymers based composite nanosystems were designed to
      provide a long-term delivery of macromolecules to the back of the eye. A unique
      arrangement of each block (polyethylene glycol, polylactic acid, and
      polycaprolactone) with various molecular weights (PB-A and PB-B) was selected for
      the synthesis of nanoparticles (NPs) and thermosensitive gel (PB-C) by sequential
      ring-opening bulk copolymerization reaction. PB copolymers were characterized for
      their molecular weight and purity by 1H-NMR spectroscopy and crystallinity by
      PXRD. The macromolecule model drugs [lysozyme (Lyz ~ 14.5 kDa), IgG-Fab (~ 50
      kDa), and IgG (~ 150 kDa)] were selected to delineate the effect of molecular
      weights on in vitro release profile of nanoformulations. Lyz-, Fab-, and IgG
      encapsulated NPs were prepared by double emulsion solvent evaporation method. The
      entrapment efficiency (EE%) and drug loading (DL%) of macromolecules was higher
      for PB-B copolymers due to its higher molecular weight and hydrophobicity compare
      to PB-A. The particle size range of NPs was ~ 200-270 nm. In vitro release
      profiles of Lyz-, Fab-, and IgG-encapsulated in NPs alone and NPs suspended in
      gel (composite nanosystem) demonstrated a minimal burst release and drug release
      over a long period. The effect of hydrodynamic diameter of macromolecules and
      hydrophobicity of PB copolymers was investigated on the release profile of
      nanosystems. In vitro biocompatibility study showed negligible cytokine (IL-1, IL
      6, and TNF-alpha) release, which confirmed the safety of the PB copolymers. Based
      on the results, it is anticipated that long-term ocular delivery of
      macromolecules can be achieved through composite nanosystems.

PMID- 29181837
TI  - Expression of liver X receptors in normal and refractory carcinoma tissues of the
      human lung and pancreas.
AB  - Liver X receptors (LXRs) participate not only in maintaining cholesterol
      homeostasis but also in controlling cellular growth in many types of normal and
      tumor cells. We previously reported that LXRalpha was aberrantly expressed in
      human oral squamous cell carcinoma (HOSCC) tissues and cell lines, and that LXR
      stimulation led to significant reduction of proliferation of HOSCC cells via
      accelerating cholesterol efflux. Since LXRs and downstream proteins involved in
      cholesterol metabolism could be also applied as therapeutic targets in small cell
      lung carcinoma (SCLC) and pancreatic ductal adenocarcinoma (PDAC), we herein
      analyzed the distribution of LXR proteins in these refractory cancers as well as
      in normal human lung and pancreatic tissues. LXRbeta was observed in ciliated
      epithelial cells, bronchial gland epithelia, type II alveolar epithelia and
      alveolar macrophages of the lung, and was less expressed in bronchial basal cells
      and type I alveolar epithelia. In addition, LXRbeta was detected in epithelium of
      the pancreatic duct and acinar cells of the pancreas, and was weakly expressed in
      pancreatic islet cells. By contrast, LXRalpha expression was restricted to
      alveolar macrophages, and was not evident in any types of epithelial cells in the
      lung and pancreas. We also demonstrated that LXRbeta but not LXRalpha was
      abundantly expressed in nine cases of SCLC and twenty cases of PDAC tissues.
      These findings provide basic information for evaluating the efficacy of LXR
      targeted treatment in SCLC and PDAC.

PMID- 29181838
TI  - Hepatitis B reactivation and outcomes in persons treated with directly acting
      antiviral agents against hepatitis C virus: results from ERCHIVES.
AB  - BACKGROUND: Higher risk of hepatitis B reactivation (HBV-r) has been reported in
      patients with hepatitis C treated with newer directly acting antiviral agents
      (DAAs). AIM: To determine the proportion of persons who develop HBV-r and its
      clinical consequences among DAA treated vs pegylated interferon/ribavirin
      (PEG/RBV) treated persons. METHODS: We calculated the proportion of persons who
      developed HBV viral reactivation (HBV-r; new detectable HBV DNA or increase of >1
      log10 ); serum alanine aminotransferase flare (>5 times baseline); all-cause
      mortality and hepatic decompensation in persons treated with a newer DAA regimen
      or PEG/RBV. Kaplan-Meier curves were used to demonstrate survival and hepatic
      decompensation by treatment group and HBV-r. RESULTS: In 34 632 persons treated
      with DAA and 23 475 treated with PEG/RBV, HBV-r rate per 1000 person-years was
      30.04 (10.41, 49.67) and 25.42 (95% CI 17.23, 33.62) respectively (P = .8). When
      stratified by SVR or by baseline HBsAg status, HBV-r was not different between
      groups. Kaplan-Meier survival curves comparing each regimen stratified by
      presence or absence of HBV-r did not demonstrate a significant difference in
      incidence of hepatic decompensation over time. For overall survival, there was no
      difference between PEG/RBV treated persons with or without HBV-r. For DAA treated
      persons, those with HBV-r had a shortened survival, though the numbers at risk
      were small. CONCLUSIONS: HBV-r is relatively uncommon after DAA therapy and not
      higher than among those treated with a PEG/RBV regimen. The small numbers of
      persons treated with a DAA regimen who do develop HBV-r have a shortened survival
      compared to those without HBV-r.

PMID- 29181839
TI  - Abdominal computed tomography angiography in post-transplantation sinusoidal
      obstruction syndrome associated with R-DHAOX/BEAM toxicity.

PMID- 29181841
TI  - Epidural therapy for the treatment of severe pre-eclampsia in non labouring
      women.
AB  - BACKGROUND: Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is
      characterised by hypertension and multisystem organ involvement and which has
      significant maternal and fetal morbidity and mortality. Failure of the placental
      vascular remodelling and reduced uteroplacental flow form the etiopathological
      basis of pre-eclampsia. There are several established therapies for pre-eclampsia
      including antihypertensives and anticonvulsants. Most of these therapies aim at
      controlling the blood pressure or preventing complications of elevated blood
      pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the
      arteries, thereby increasing uteroplacental blood flow. This review was aimed at
      evaluating the available evidence about the possible benefits and risks of
      epidural therapy in the management of severe pre-eclampsia, to define the current
      evidence level of this therapy, and to determine what (if any) further evidence
      is required. OBJECTIVES: To assess the effectiveness, safety and cost of the
      extended use of epidural therapy for treating severe pre-eclampsia in non
      labouring women. This review aims to compare the use of extended epidural therapy
      with other methods, which include intravenous magnesium sulphate, anticonvulsants
      other than magnesium sulphate, with or without use of the antihypertensive drugs
      and adjuncts in the treatment of severe pre-eclampsia.This review only considered
      the use of epidural anaesthesia in the management of severe pre-eclampsia in the
      antepartum period and not as pain relief in labour. SEARCH METHODS: We searched
      Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the
      WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and
      reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy
      for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium
      sulphate, low-dose dopamine, corticosteroids or a combination of these, were
      eligible for inclusion. Trials using a cluster design, and studies published in
      abstract form only are also eligible for inclusion in this review. Cross-over
      trials were not eligible for inclusion in this review. DATA COLLECTION AND
      ANALYSIS: The two review authors independently assessed trials for inclusion and
      trial quality. There were no relevant data available for extraction. MAIN
      RESULTS: We included one small study (involving 24 women). The study was a single
      centre randomised trial conducted in Mexico. This study compared a control group
      who received antihypertensive therapy, anticonvulsant therapy, plasma expanders,
      corticosteroids and dypyridamole with an intervention group that received
      epidural block instead of the antihypertensives, as well as all the other four
      drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5
      mg each hour on continuous epidural infusion for six hours. This study was at low
      risk of bias in three domains but was assessed to be high risk of bias in two
      domains due to lack of allocation concealment and blinding of women and staff,
      and unclear for random sequence generation and outcome assessor blinding.The
      included study did not report on any of this review's important outcomes. Meta
      analysis was not possible.For the mother, these were: maternal death (death
      during pregnancy or up to 42 days after the end of the pregnancy, or death more
      than 42 days after the end of the pregnancy); development of eclampsia or
      recurrence of seizures; stroke; any serious morbidity: defined as at least one of
      stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver
      enzymes and low platelets), disseminated intravascular coagulation, pulmonary
      oedema.For the baby, these were: death: stillbirths (death in utero at or after
      20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week
      of life), death before discharge from the hospital, neonatal deaths (death within
      the first 28 days after birth), deaths after the first 28 days; preterm birth
      (defined as the birth before 37 completed weeks' gestation); and side effects of
      the intervention. Reported outcomesThe included study only reported on a single
      secondary outcome of interest to this review: the Apgar score of the baby at
      birth and after five minutes and there was no clear difference between the
      intervention and control groups.The included study also reported a reduction in
      maternal diastolic arterial pressure. However, the change in maternal mean
      arterial pressure and systolic arterial pressure, which were the other reported
      outcomes of this trial, were not significantly different between the two groups.
      AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence from randomised
      controlled trials to evaluate the effectiveness, safety or cost of using epidural
      therapy for treating severe pre-eclampsia in non-labouring women.High-quality
      randomised controlled trials are needed to evaluate the use of epidural agents as
      therapy for treatment of severe pre-eclampsia. The rationale for the use of
      epidural is well-founded. However there is insufficient evidence from randomised
      controlled trials to show that the effect of epidural translates into improved
      maternal and fetal outcomes. Thus, there is a need for larger, well-designed
      studies to come to an evidence-based conclusion as to whether the lowering of
      vasomotor tone by epidural therapy results in better maternal and fetal outcomes
      and for how long that could be maintained. Another important question that needs
      to be answered is how long should extended epidural be used to ensure any
      potential clinical benefits and what could be the associated side effects and
      costs. Interactions with other modalities of treatment and women's satisfaction
      could represent other avenues of research.

PMID- 29181840
TI  - MYD88 wild-type Waldenstrom Macroglobulinaemia: differential diagnosis, risk of
      histological transformation, and overall survival.
AB  - MYD88 mutations are present in 95% of Waldenstrom Macroglobulinaemia (WM)
      patients, and support diagnostic discrimination from other IgM-secreting B-cell
      malignancies. Diagnostic discrimination can be difficult among suspected wild
      type MYD88 (MYD88WT ) WM cases. We systematically reviewed the clinical,
      pathological and laboratory studies for 64 suspected MYD88WT WM patients. World
      Health Organization and WM consensus guidelines were used to establish
      clinicopathological diagnosis. Up to 30% of suspected MYD88WT WM cases had an
      alternative clinicopathological diagnosis, including IgM multiple myeloma. The
      estimated 10-year survival was 73% (95% confidence interval [CI] 52-86%) for
      MYD88WT versus 90% (95% CI 82-95%) for mutated (MYD88MUT ) WM patients (Log-rank
      P < 0.001). Multivariate analysis only showed MYD88 mutation status (P < 0.001)
      as a significant determinant for overall survival. Diffuse large B-cell lymphoma
      (DLBCL) was diagnosed in 7 (15.2%) and 2 (0.76%) of MYD88WT and MYD88MUT
      patients, respectively (Odds ratio 23.3; 95% CI 4.2-233.8; P < 0.001). Overall
      survival was shorter among MYD88WT patients with an associated DLBCL event (Log
      rank P = 0.08). The findings show that among suspected MYD88WT WM cases, an
      alternative clinicopathological diagnosis is common and can impact clinical care.
      WM patients with MYD88WT disease have a high incidence of associated DLBCL events
      and significantly shorter survival versus those with MYD88MUT disease.

PMID- 29181842
TI  - Sofosbuvir and velpatasvir with or without voxilaprevir in direct-acting
      antiviral-naive chronic hepatitis C: patient-reported outcomes from POLARIS 2 and
      3.
AB  - BACKGROUND: Chronic hepatitis C infection leads to impairment of patient-reported
      outcomes (PROs). Treatment with direct-acting antiviral regimens results in short
      and long-term improvement of these outcomes. AIM: To assess PROs in patients
      treated with a newly developed direct-acting antiviral, a fixed-dose combination
      of sofosbuvir/velpatasvir (SOF/VEL) with/without voxilaprevir (VOX). METHODS: The
      PRO data were collected from participants of POLARIS-2 and POLARIS-3 clinical
      trials (DAA-naive, all HCV genotypes). Participants self-administered SF-36v2,
      FACIT-F, CLDQ-HCV and WPAI:SHP instruments at baseline, during treatment, and in
      follow-up. RESULTS: Of 1160 patients, 611 received SOF/VEL/VOX and 549 received
      SOF/VEL (52.8 +/- 11.0 years, 55.9% male, 75.4% treatment-naive, 33.9%
      cirrhotic). The sustained viral response at 12 weeks (SVR12) rates were 95%-98%.
      During treatment, improvements in most PRO scores were significant (all but one P
      < .01) and ranged from, on average, +2.3 to +15.0 points (on a 0-100 scale) by
      the end of treatment. These improvements were similar between SOF/VEL/VOX and
      SOF/VEL arms (all P > .05). After treatment discontinuation, patients treated
      with both regimens achieved significant and clinically meaningful PRO gains (+2.7
      to +16.7 by post-treatment week 12, +3.9 to +20.1 by post-treatment week 24; all
      but one P < .001). Multivariate analysis showed that depression, anxiety and
      cirrhosis were the most consistent independent predictors of PRO impairment while
      no association of PROs with the treatment regimen choice was found (all P > .05).
      CONCLUSIONS: The pan-genotypic regimens with SOF/VEL with or without VOX not only
      have excellent efficacy and safety, but also significantly positively impact
      patients' experience both during treatment and after achieving sustained
      virologic response in DAA-naive patients with HCV.

PMID- 29181844
TI  - Comparative efficacy of endodontic medicaments and sodium hypochlorite against
      Enterococcus faecalis biofilms.
AB  - BACKGROUND: Many studies have investigated the effectiveness of root canal
      irrigants and medicaments against Enterococcus faecalis. The aim of this study
      was to compare the efficacy of commonly used medicaments against E. faecalis
      cultured as a biofilm on dentine substrate. METHODS: An E. faecalis biofilm was
      established on human dentine slices using a continuous flow cell. Each test
      medicament (Ledermix, Ca(OH)2 , Odontopaste, 0.2% chlorhexidine and 50:50
      combinations of Ledermix/Ca(OH)2 and Odontopaste/Ca(OH)2 ) was introduced into
      the flow cell and biofilms were harvested and quantitated by determining cellular
      protein. Cellular viability was determined using serial plating and the number of
      colony-forming units was normalized against cellular protein to allow treatment
      protocols to be compared. Qualitative scanning electron microscopy analyses of
      the biofilm were performed after a 48-h exposure to each test agent. RESULTS:
      Sodium hypochlorite achieved total bacterial elimination. Ledermix and
      Odontopaste had no significant effect on the E. faecalis biofilm. Ca(OH)2 and
      50:50 combinations of Ca(OH)2 /Ledermix or Ca(OH)2 /Odontopaste reduced the
      viability by more than 99% while 0.2% chlorhexidine reduced bacterial numbers by
      97%. CONCLUSIONS: Sodium hypochlorite remains the gold standard for bacterial
      elimination in root canal therapy. However, Ca(OH)2 in isolation and combined
      with Ledermix, and Odontopaste was highly effective in reducing bacterial
      viability.

PMID- 29181843
TI  - Genetic factors influencing prostate cancer risk in Norwegian men.
AB  - Norway has one of the highest rates of death due to prostate cancer (PCa) in the
      world. To assess the contribution of both common and rare single nucleotide
      variants (SNPs) to the prostate cancer burden in Norway, we assessed the
      frequency of the established prostate cancer susceptibility allele, HOXB13 G84E,
      as well as a series of validated, common PCa risk SNPs in a Norwegian PCa
      population of 779 patients. The G84E allele was observed in 2.3% of patients
      compared to 0.7% of control individuals, OR = 3.8, P = 1 * 10-4. While there was
      a trend toward an earlier age at diagnosis, overall the clinicopathologic
      features of PCa were not significantly different in G84E carriers and non
      carriers. Evaluation of 32 established common risk alleles revealed significant
      associations of risk alleles at 13 loci, including SNPs at 8q24, and near TET2,
      SLC22A3, NKX3-1, CASC8, MYC, DAP2IP, MSMB, HNF1B, PPP1R14A, and KLK2/3. When the
      data for each SNP are combined into a genetic risk score (GRS), Norwegian men
      within the top decile of GRS have over 5-fold greater risk to be diagnosed with
      PCa than men with GRS in the lowest decile. These results indicate that risk
      alleles of HOXB13 and common variant SNPs are important components of inherited
      PCa risk in the Norwegian population, although these factors appear to contribute
      little to the malignancy's aggressiveness.

PMID- 29181845
TI  - Interventions for preventing oral mucositis in patients with cancer receiving
      treatment: cytokines and growth factors.
AB  - BACKGROUND: Oral mucositis is a side effect of chemotherapy, head and neck
      radiotherapy, and targeted therapy, affecting over 75% of high-risk patients.
      Ulceration can lead to severe pain and difficulty with eating and drinking, which
      may necessitate opioid analgesics, hospitalisation and supplemental nutrition.
      These complications may disrupt cancer therapy, which may reduce survival. There
      is also a risk of death from sepsis if pathogens enter the ulcers of
      immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare
      systems, yet there are few preventive interventions proven to be beneficial.
      Cytokines and growth factors may help the regeneration of cells lining of the
      mouth, thus preventing or reducing oral mucositis and its negative effects.
      OBJECTIVES: To assess the effects of cytokines and growth factors for preventing
      oral mucositis in patients with cancer who are receiving treatment. SEARCH
      METHODS: Cochrane Oral Health's Information Specialist searched the following
      databases: Cochrane Oral Health's Trials Register (searched 10 May 2017); the
      Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4) in the
      Cochrane Library (searched 10 May 2017); MEDLINE Ovid (1946 to 10 May 2017);
      Embase Ovid (7 December 2015 to 10 May 2017); CINAHL EBSCO (Cumulative Index to
      Nursing and Allied Health Literature; 1937 to 10 May 2017); and CANCERLIT PubMed
      (1950 to 10 May 2017). The US National Institutes of Health Ongoing Trials
      Register (ClinicalTrials.gov) and the World Health Organization International
      Clinical Trials Registry Platform were searched for ongoing trials. SELECTION
      CRITERIA: We included parallel-design randomised controlled trials (RCTs)
      assessing the effects of cytokines and growth factors in patients with cancer
      receiving treatment. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened the results of electronic searches, extracted data and
      assessed risk of bias. For dichotomous outcomes, we reported risk ratios (RR) and
      95% confidence intervals (CI). For continuous outcomes, we reported mean
      differences (MD) and 95% CIs. We pooled similar studies in random-effects meta
      analyses. We reported adverse effects in a narrative format. MAIN RESULTS: We
      included 35 RCTs analysing 3102 participants. Thirteen studies were at low risk
      of bias, 12 studies were at unclear risk of bias, and 10 studies were at high
      risk of bias.Our main findings were regarding keratinocyte growth factor (KGF)
      and are summarised as follows.There might be a reduction in the risk of moderate
      to severe oral mucositis in adults receiving bone marrow/stem cell
      transplantation after conditioning therapy for haematological cancers (RR 0.89,
      95% CI 0.80 to 0.99; 6 studies; 852 participants; low-quality evidence). We would
      need to treat 11 adults with KGF in order to prevent one additional adult from
      developing this outcome (95% CI 6 to 112). There might be a reduction in the risk
      of severe oral mucositis in this population, but there is also some possibility
      of an increase in risk (RR 0.85, 95% CI 0.65 to 1.11; 6 studies; 852
      participants; low-quality evidence). We would need to treat 10 adults with KGF in
      order to prevent one additional adult from developing this outcome (95% CI 5 to
      prevent the outcome to 14 to cause the outcome).There is probably a reduction in
      the risk of moderate to severe oral mucositis in adults receiving radiotherapy to
      the head and neck with cisplatin or fluorouracil (RR 0.91, 95% CI 0.83 to 1.00; 3
      studies; 471 participants; moderate-quality evidence). We would need to treat 12
      adults with KGF in order to prevent one additional adult from developing this
      outcome (95% CI 7 to infinity). It is very likely that there is a reduction in
      the risk of severe oral mucositis in this population (RR 0.79, 95% CI 0.69 to
      0.90; 3 studies; 471 participants; high-quality evidence). We would need to treat
      7 adults with KGF in order to prevent one additional adult from developing this
      outcome (95% CI 5 to 15).It is likely that there is a reduction in the risk of
      moderate to severe oral mucositis in adults receiving chemotherapy alone for
      mixed solid and haematological cancers (RR 0.56, 95% CI 0.45 to 0.70; 4 studies;
      344 participants; moderate-quality evidence). We would need to treat 4 adults
      with KGF in order to prevent one additional adult from developing this outcome
      (95% CI 3 to 6). There might be a reduction in the risk of severe oral mucositis
      in this population (RR 0.30, 95% CI 0.14 to 0.65; 3 studies; 263 participants;
      low -quality evidence). We would need to treat 10 adults with KGF in order to
      prevent one additional adult from developing this outcome (95% CI 8 to 19).Due to
      the low volume of evidence, single-study comparisons and insufficient sample
      sizes, we found no compelling evidence of a benefit for any other cytokines or
      growth factors and there was no evidence on children. There did not appear to be
      any serious adverse effects of any of the interventions assessed in this review.
      AUTHORS' CONCLUSIONS: We are confident that KGF is beneficial in the prevention
      of oral mucositis in adults who are receiving: a) radiotherapy to the head and
      neck with cisplatin or fluorouracil; or b) chemotherapy alone for mixed solid and
      haematological cancers. We are less confident about a benefit for KGF in adults
      receiving bone marrow/stem cell transplant after conditioning therapy for
      haematological cancers because of multiple factors involved in that population,
      such as whether or not they received total body irradiation (TBI) and whether the
      transplant was autologous (the patients' own cells) or allogeneic (cells from a
      donor). KGF appears to be a relatively safe intervention.Due to limited research,
      we are not confident that there are any beneficial effects of other cytokines and
      growth factors. There is currently insufficient evidence to draw any conclusions
      about the use of cytokines and growth factors in children.

PMID- 29181846
TI  - GOLM1 promotes prostate cancer progression through activating PI3K-AKT-mTOR
      signaling.
AB  - BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed cancer in men.
      Various molecular mechanisms account for PCa progression and elucidation of these
      mechanisms is key for selection of optimal therapies and improvement of patient
      outcome. Golgi membrane protein 1 (GOLM1) has been identified as a novel
      biomarker for PCa, but its biological functions and molecular mechanisms remain
      poorly understood. METHOD: GOLM1 expression was determined in PCa by tissue
      microarrays (TMAs) and real-time RT-PCR, Western blot, and immunohistochemistry
      (IHC) analyses. To investigate GOLM1 functions in vitro and in vivo, we
      overexpressed and knocked down GOLM1 in PCa cell lines and established xenograft
      mice models. A series of cytological function assays were used to determine the
      role of GOLM1 in cell proliferation, migration, invasion, and apoptosis. PI3K-AKT
      mTOR signaling pathway downstream of GOLM1 was detected by Western blot and IHC
      analyses. RESULT: GOLM1 expression is up-regulated in PCa of all stages and
      grades. GOLM1 promotes proliferation, migration and invasion, and inhibits
      apoptosis in PCa cell lines (DU145, PC3, and CWR22Rv1) and xenograft mice models.
      Moreover, PI3K-AKT-mTOR signaling is positively regulated by GOLM1, whereas PI3 K
      inhibitor BKM120 significantly abrogates the oncogenic functions of GOLM1.
      CONCLUSION: GOLM1 acts as a critical oncogene by promoting PCa cell
      proliferation, migration and invasion, and inhibiting apoptosis. GOLM1 plays
      oncogenic functions mainly through activating PI3K-AKT-mTOR signaling pathway.
      Therefore, agents that block PI3K-AKT-mTOR signaling pathway could be used in PCa
      patients with GOLM1 up-regulation.

PMID- 29181847
TI  - Achyranthes bidentata polypeptide protects dopaminergic neurons from apoptosis in
      Parkinson's disease models both in vitro and in vivo.
AB  - BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder
      closely associated with dopaminergic neuron loss. It is well documented that
      Achyranthes bidentata polypeptides (ABPP) are potent neuroprotective agents in
      several kinds of neurons. Therefore, we proposed that ABPP might play a
      beneficial role against PD by protecting dopaminergic neurons from apoptosis.
      EXPERIMENTAL APPROACH: SH-SY5Y cells and primary rat dopaminergic neurons were
      pretreated with ABPP fraction k (ABPPk), a purified fraction of ABPP, and then
      the cells were exposed to 1-methyl-4-phenylpyridinium iodide (MPP+ ) to induce
      apoptosis. Cell viability, LDH activity, a Tunel assay and protein levels of Bcl
      2 and Bax were analysed. In an in vivo PD model induced by MPTP, ABPPk was
      intranasally delivered to mice. Behavioural tests, immunohistochemistry,
      immunostaining, Nissl staining, qRT-PCR and Western blot were employed to
      evaluate the potential effects of ABPPk on PD in mice. KEY RESULTS: The
      application of ABPPk markedly enhanced the viability of SH-SY5Y cells and primary
      dopaminergic neurons treated with neurotoxic agent MPP+ . In an in vivo MPTP
      induced PD model, ABPPk significantly improved behavioural performances and
      prevented tyrosine hydroxylase loss in the substantia nigra pars compacta and
      striatum. Furthermore, we showed that MPTP-induced astrocyte and microglia
      activation were largely attenuated by ABPPk, leading to low levels of
      neuroinflammation and a downregulation of the apoptotic signalling pathway.
      CONCLUSION AND IMPLICATIONS: Taken together, our data show that ABPPk protects
      dopaminergic neurons from apoptosis, suggesting that ABPPk might be an effective
      intervention for treating the neuron loss associated with disorders such as PD.

PMID- 29181848
TI  - Linked color imaging identified ulcerative colitis-associated colorectal cancer:
      A case report.

PMID- 29181849
TI  - The walking dead: sequential nuclear and organelle destruction during hair
      development.
AB  - BACKGROUND: Transition of hair shaft keratinocytes from actively respiring,
      nucleated cells to structural cells devoid of nucleus and cytoplasm is key to
      hair production. This form of cell 'death', or cornification, requires cellular
      organelle removal to allow the cytoplasm to become packed with keratin filament
      bundles that further require cross-linking to create a strong hair fibre.
      Although these processes are well described in epidermal keratinocytes, there is
      a lack of understanding of such mechanisms, specifically in the hair follicle.
      OBJECTIVES: To gain insights into cornification mechanisms within the hair
      follicle and thus improve our understanding of normal hair physiology. METHODS:
      Scalp biopsies and hair-pluck samples were obtained from healthy human donors and
      analysed microscopically after immunohistochemical staining. RESULTS: A focal
      point of respiratory activity was evident in keratogenous zone cells within the
      hair shaft, which also exhibited nuclear damage. Nuclear degradation occurred via
      both caspase-dependent and caspase-independent pathways. Conversely, mitophagy
      was driven by Bnip3L and restricted to the boundary of the keratogenous zone at
      Adamson's Fringe. CONCLUSIONS: We propose a model of stepwise living-dead
      transition within the first 1 mm of hair formation, whereby fully functional,
      nucleated cells first consolidate required functions by degrading nuclear DNA,
      yet continue to respire and provide the source of reactive oxygen species
      required for keratin cross-linking. Finally, as the cells become packed with
      keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the
      last remaining 'living' characteristic, thus completing the march from 'living'
      to 'dead' within the hair follicle.

PMID- 29181851
TI  - Life course evolution of body size and breast cancer survival in the E3N cohort.
AB  - Although adult obesity has been associated with poor breast cancer survival, data
      on adiposity at different periods in life and its lifelong evolution are scarce.
      Our aims were to assess the associations between breast cancer survival and body
      size during childhood, puberty and early adulthood and body size trajectories
      from childhood to adulthood. Self-assessed body size at age 8, at puberty, at age
      20-25 and at age 35-40 and trajectories of body size of 4,662 breast cancer
      survivors from the prospective E3N cohort were studied in relation to risk of
      death from any cause, death from breast cancer and second invasive cancer event
      using multivariate Cox regression models. Four trajectories of body size were
      identified (T1 "moderate increase," T2 "stable/low increase," T3 "increase at
      puberty" and T4 "constantly high"). Compared with stable body size, an increase
      in body size during adult life was associated with an increased risk of death
      from any cause (HR T1 vs. T2 = 1.27; 95% CI = 1.01-1.60) and an increased risk of
      second invasive cancer event (HR T1 vs. T2 = 1.25; 95% CI = 1.06-1.47).
      Silhouettes at various ages were not associated with survival. Our results
      suggest that the evolution of body size from childhood to adulthood has a long
      term influence on breast cancer survival. Although these results need to be
      confirmed, this work sheds light on the need to combine lifelong approaches to
      current BMI to better identify breast cancer survivors who are at higher risk of
      recurrence or second primary cancer, or of death.

PMID- 29181850
TI  - Can non-clinical repolarization assays predict the results of clinical thorough
      QT studies? Results from a research consortium.
AB  - BACKGROUND AND PURPOSE: Translation of non-clinical markers of delayed
      ventricular repolarization to clinical prolongation of the QT interval corrected
      for heart rate (QTc) (a biomarker for torsades de pointes proarrhythmia) remains
      an issue in drug discovery and regulatory evaluations. We retrospectively
      analysed 150 drug applications in a US Food and Drug Administration database to
      determine the utility of established non-clinical in vitro IKr current human
      ether-a-go-go-related gene (hERG), action potential duration (APD) and in vivo
      (QTc) repolarization assays to detect and predict clinical QTc prolongation.
      EXPERIMENTAL APPROACH: The predictive performance of three non-clinical assays
      was compared with clinical thorough QT study outcomes based on free clinical
      plasma drug concentrations using sensitivity and specificity, receiver operating
      characteristic (ROC) curves, positive (PPVs) and negative predictive values
      (NPVs) and likelihood ratios (LRs). KEY RESULTS: Non-clinical assays demonstrated
      robust specificity (high true negative rate) but poor sensitivity (low true
      positive rate) for clinical QTc prolongation at low-intermediate (1*-30*)
      clinical exposure multiples. The QTc assay provided the most robust PPVs and NPVs
      (ability to predict clinical QTc prolongation). ROC curves (overall test
      accuracy) and LRs (ability to influence post-test probabilities) demonstrated
      overall marginal performance for hERG and QTc assays (best at 30* exposures),
      while the APD assay demonstrated minimal value. CONCLUSIONS AND IMPLICATIONS: The
      predictive value of hERG, APD and QTc assays varies, with drug concentrations
      strongly affecting translational performance. While useful in guiding preclinical
      candidates without clinical QT prolongation, hERG and QTc repolarization assays
      provide greater value compared with the APD assay.

PMID- 29181852
TI  - Optimal injection solution for endoscopic submucosal dissection: A randomized
      controlled trial of Western solutions in a porcine model.
AB  - BACKGROUND AND AIM: When carrying out endoscopic submucosal dissection (ESD),
      procedural safety increases with greater tissue elevation and efficiency
      increases with longer-lasting submucosal cushion. Fluids specifically developed
      for ESD in Asia are not commercially available in the West, leaving endoscopists
      to use a variety of injectable fluids off-label. To determine the optimal fluid
      available in the West, we compared commonly used fluids for Western ESD. METHODS:
      All phases were carried out in an ex vivo porcine stomach model. Phase 1 compared
      tissue elevation and duration of submucosal cushions produced by various standard
      volumes of various injectable solutions used for ESD. The two best-performing
      solutions used off-label were tested head-to-head in ESD in Phase 2. Phase 3
      compared the best solution from Phase 2 to Eleview(r) , currently the only
      submucosal injection fluid approved in the USA. In Phases 2 and 3, five ESD were
      carried out with each solution. The solutions were randomized and the endoscopist
      blinded to the solution. RESULTS: The best-performing solutions in Phase 1 were
      0.4% hyaluronic acid, 6% hydroxyethyl starch (HES), and Eleview(r) . Phase 2
      compared 6% HES and hydroxypropyl methylcellulose (HPMC), showing that ESD with
      6% HES was easier (P = 0.007), faster (P = 0.041) and required less injection
      volume (P = 0.003). In Phase 3, resection speed, ease of ESD and total volume per
      area resected were comparable between 6% HES and Eleview(r) . CONCLUSIONS: Of the
      submucosal injection fluids currently available in the West, Eleview(r) and 6%
      HES are the best-performing solutions for ESD in a porcine model.

PMID- 29181854
TI  - Assessing the similarity of dose response and target doses in two non-overlapping
      subgroups.
AB  - We consider 2 problems of increasing importance in clinical dose finding studies.
      First, we assess the similarity of 2 non-linear regression models for 2 non
      overlapping subgroups of patients over a restricted covariate space. To this end,
      we derive a confidence interval for the maximum difference between the 2 given
      models. If this confidence interval excludes the pre-specified equivalence
      margin, similarity of dose response can be claimed. Second, we address the
      problem of demonstrating the similarity of 2 target doses for 2 non-overlapping
      subgroups, using again an approach based on a confidence interval. We illustrate
      the proposed methods with a real case study and investigate their operating
      characteristics (coverage probabilities, Type I error rates, power) via
      simulation.

PMID- 29181853
TI  - Toward the elimination of hepatitis C in the United States.
AB  - The emergence of effective direct-acting antiviral (DAA) agents has reignited
      discussion over the potential for hepatitis C elimination in the United States.
      Eliminating hepatitis C will require a critical examination of technical
      feasibility, economic considerations, and social/political attention. Tremendous
      advancement has been made with the availability of sensitive diagnostic tests and
      highly effective DAAs capable of achieving sustained viral response (SVR) in more
      than 95% of patients. Eliminating hepatitis C also requires escalating existing
      surveillance networks to monitor for new epidemics. All preventive interventions
      such as clean syringe and needle exchange programs, safe injection sites, opioid
      substitution therapies, and mental health services need to be expanded. Although
      costs of DAAs have raised budget concerns for hepatitis C elimination, studies
      have shown that eliminating hepatitis C will produce a savings of up to 6.5
      billion USD annually along with other intangible benefits such as increased work
      productivity and quality of life. Economic models and meta-analyses strongly
      suggest universal hepatitis C screening for all adults rather than just for birth
      cohort and high-risk populations. Social and political factors are at least as
      important as technical feasibility and economic considerations. Due to lack of
      promotion and public awareness, HCV elimination efforts continue to receive
      inadequate funding. Social stigma continues to impede meaningful policy changes.
      Eliminating hepatitis C is an attainable public health goal that will require
      intense collaboration and sustained public support. (Hepatology 2018;67:2449
      2459).

PMID- 29181855
TI  - Liposomal encapsulation of silver nanoparticles enhances cytotoxicity and causes
      induction of reactive oxygen species-independent apoptosis.
AB  - Silver nanoparticles (AgNP) are one of the most widely investigated metallic NPs
      due to their promising antibacterial activities. In recent years, AgNP research
      has shifted beyond antimicrobial use to potential applications in the medical
      arena. This shift coupled with the extensive commercial applications of AgNP will
      further increase human exposure and the subsequent risk of adverse effects that
      may result from repeated exposures and inefficient delivery, meaning research
      into improved AgNP delivery is of paramount importance. In this study, AgNP were
      encapsulated in a natural biosurfactant, dipalmitoylphosphatidylcholine, in an
      attempt to enhance the intracellular delivery and simultaneously mediate the
      associated cytotoxicity of the AgNP. It was noted that because of the
      encapsulation, liposomal AgNP (Lipo-AgNP) at 0.625 MUg ml-1 induced significant
      cell death in THP1 cell lines a notably lower dose than that of the uncoated AgNP
      induced cytotoxicity. The induced cytotoxicity was shown to result in an
      increased level of DNA fragmentation resulting in a cell cycle interruption at
      the S phase. It was shown that the predominate form of cell death upon exposure
      to both uncoated AgNP and Lipo-AgNP was apoptosis. However, a reactive oxygen
      species-independent activation of the executioner caspases 3/7 occurred when
      exposed to the Lipo-AgNP. These findings showed that encapsulation of AgNP
      enhance AgNP cytotoxicity and mediates a reactive oxygen species-independent
      induction of apoptosis.

PMID- 29181856
TI  - Nanoconfined Oxidation Synthesis of N-Doped Carbon Hollow Spheres and MnO2
      Encapsulated Sulfur Cathode for Superior Li-S Batteries.
AB  - The sulfur cathode, as a new generation of lithium-ion battery cathode material,
      has a high theoretical energy density of about 2500 Wh kg-1 . However, the low
      conductivity of sulfur and the "shuttle effect", widely presenting in the
      lithiation/de-lithiation process, seriously hinder its practical application.
      Here, we report a new nanoconfined oxidation route (first complete oxidation of
      metal sulfide and subsequently partial oxidation of the generated S from sulfide)
      for S cathode encapsulated with MnO2 nanosheets and N-doped carbon hollow
      spheres. This nanoconfined oxidation route can successfully confine the sulfur
      particles in the interior of the carbon shell, and the rationally introduced
      nonpolar carbon and polar MnO2 can both reduce the dissolution of polysulfide
      during the charge-discharge process. The obtained well-defined S-MnO2 @C cathode
      exhibits high specific capacity with excellent cycling performance and superior
      rate capability.

PMID- 29181858
TI  - Relationship between salivary haemoglobin and number of remaining teeth in older
      Koreans.
AB  - OBJECTIVE: We investigated the relationship between saliva and dental biofilm
      characteristics, oral hygiene behaviours and the number of remaining teeth in a
      sample of older Koreans. MATERIALS AND METHODS: This cross-sectional study
      included 133 participants, aged 65 years and older, recruited from senior welfare
      facilities in Incheon, South Korea. The outcome variable was the number of
      remaining teeth, and its associations with the independent variables of
      participants' general characteristics, salivary haemoglobin level, dental biofilm
      acidogenicity, salivary flow rate and oral hygiene behaviours were assessed. For
      statistical analyses, chi-squared test and step-wise multiple linear regression
      were used. RESULTS: The multiple linear regression model, which included all
      related factors identified in the bivariate analyses, showed that older adults
      who had high salivary haemoglobin levels (P < .05), brushed their teeth using the
      horizontal scrub method (P< .001), and did not use an interproximal cleaning
      device (P < .01) were more likely to have fewer remaining teeth. However, dental
      biofilm acidogenicity was not associated with the number of remaining teeth.
      CONCLUSION: The number of remaining teeth was associated with salivary
      haemoglobin level, appropriate toothbrushing technique and interdental cleaning.
      These findings suggest that the monitoring of salivary haemoglobin may contribute
      to the prevention of tooth loss caused by periodontal disease.

PMID- 29181857
TI  - Whole-exome sequencing of the BDR cohort: evidence to support the role of the
      PILRA gene in Alzheimer's disease.
AB  - AIM: Late-onset Alzheimer's disease (LOAD) accounts for 95% of all Alzheimer's
      cases and is genetically complex in nature. Overlapping clinical and
      neuropathological features between AD, FTD and Parkinson's disease highlight the
      potential role of genetic pleiotropy across diseases. Recent genome-wide
      association studies (GWASs) have uncovered 20 new loci for AD risk; however,
      these exhibit small effect sizes. Using NGS, here we perform association analyses
      using exome-wide and candidate-gene-driven approaches. METHODS: Whole-exome
      sequencing was performed on 132 AD cases and 53 control samples. Exome-wide
      single-variant association and gene burden tests were performed for 76 640
      nonsingleton variants. Samples were also screened for known causative mutations
      in familial genes in AD and other dementias. Single-variant association and
      burden analysis was also carried out on variants in known AD and other
      neurological dementia genes. RESULTS: Tentative single-variant and burden
      associations were seen in several genes with kinase and protease activity. Exome
      wide burden analysis also revealed significant burden of variants in PILRA (P =
      3.4 * 10-5 ), which has previously been linked to AD via GWAS, hit ZCWPW1.
      Screening for causative mutations in familial AD and other dementia genes
      revealed no pathogenic variants. Variants identified in ABCA7, SLC24A4, CD33 and
      LRRK2 were nominally associated with disease (P < 0.05) but did not withstand
      correction for multiple testing. APOE (P = 0.02) and CLU (P = 0.04) variants
      showed significant burden on AD. CONCLUSIONS: In addition, polygenic risk scores
      (PRS) were able to distinguish between cases and controls with 83.8% accuracy
      using 3268 variants, sex, age at death and APOE epsilon4 and epsilon2 status as
      predictors.

PMID- 29181859
TI  - Tumor invasion to the arteries feeding the gallbladder as a novel risk factor for
      cholecystitis after metallic stent placement in distal malignant biliary
      obstruction.
AB  - BACKGROUND AND AIM: Cholecystitis is a major complication after self-expandable
      metallic stent (SEMS) placement for malignant biliary obstruction. Ischemia is
      one of the risk factors for cholecystitis, but little is known about the
      influence of tumor invasion to the feeding artery of the gallbladder on the onset
      of cholecystitis after SEMS placement. The aim of the present study was to
      identify risk factors for cholecystitis after SEMS placement. METHODS: Incidence
      and nine predictive factors of cholecystitis were retrospectively evaluated in
      107 patients who underwent SEMS placement for unresectable distal malignant
      biliary obstruction at Kyoto University Hospital and Otsu Red Cross Hospital
      between January 2012 and June 2016. RESULTS: Cholecystitis occurred in 13 of 107
      patients (12.1%) after SEMS placement during the median follow-up period of 262
      days. Univariate analyses showed that tumor invasion to the feeding artery of the
      gallbladder and tumor involvement to the orifice of the cystic duct were
      significant predictors of cholecystitis (P = 0.001 and P < 0.001). Multivariate
      analysis confirmed that these two factors were significant and independent risks
      for cholecystitis with odds ratios of 22.13 (95% CI, 3.57-137.18; P = 0.001) and
      25.26 (95% CI, 4.12-154.98; P < 0.001), respectively. CONCLUSIONS: This study
      showed for the first time that tumor invasion to the feeding artery of the
      gallbladder as well as tumor involvement to the orifice of the cystic duct are
      independent risk factors for cholecystitis after SEMS placement.

PMID- 29181860
TI  - Detection of Helicobacter pylori in stool samples of young children using real
      time polymerase chain reaction.
AB  - BACKGROUND: The aims of this study were to develop and validate a multiplex real
      time polymerase chain reaction (q-PCR) assay of Helicobacter pylori in stool
      samples of healthy children. Additionally, we determined the prevalence of
      clarithromycin resistance and cagA gene in H. pylori-positive samples. MATERIALS
      AND METHODS: Archived stool samples from 188 children aged 6-9 years and 272
      samples of 92 infants aged 2-18 months were tested for H. pylori antigens using
      enzyme immunoassay (EIA). A multiplex q-PCR assay was designed to detect H.
      pylori 16S rRNA and urease and the human RNase P gene as an internal control.
      Kappa coefficient was calculated to assess the agreement between q-PCR and EIA.
      RESULTS: Laboratory validation of the q-PCR assay using quantitated H. pylori
      ATCC 43504 extracted DNA showed S-shaped amplification curves for all genes; the
      limit of detection was 1 CFU/reaction. No cross-reactivity with other bacterial
      pathogens was noted. Applying the multiplex q-PCR to DNA extracted from fecal
      samples showed clear amplification curves for urease gene, but not for 16S rRNA.
      The prevalence of H. pylori infection was 50% (95% CI 43%-57%) by q-PCR (urease
      cycle threshold <44) vs 59% (95% CI 52%-66%) by EIA. Kappa coefficient was .80 (P
      < .001) and .44 (P < .001) for children aged 6-9 years and 2-18 months,
      respectively. Sixteen samples were positive for cagA and three were positive for
      clarithromycin resistance mutation (A2143G) as confirmed by sequencing.
      CONCLUSIONS: The developed q-PCR can be used as a cotechnique to enhance the
      accuracy of H. pylori detection in epidemiological studies and in clinical
      settings.

PMID- 29181861
TI  - Aneuploidy, TP53 mutation, and amplification of MYC correlate with increased
      intratumor heterogeneity and poor prognosis of breast cancer patients.
AB  - The clinical course of breast cancer varies from one patient to another.
      Currently, the choice of therapy relies on clinical parameters and histological
      and molecular tumor features. Alas, these markers are informative in only a
      subset of patients. Therefore, additional predictors of disease outcome would be
      valuable for treatment stratification. Extensive studies showed that the degree
      of variation of the nuclear DNA content, i.e., aneuploidy, determines prognosis.
      Our aim was to further elucidate the molecular basis of aneuploidy. We analyzed
      five diploid and six aneuploid tumors with more than 20 years of follow-up. By
      performing FISH with a multiplexed panel of 10 probes to enumerate copy numbers
      in individual cells, and by sequencing 563 cancer-related genes, we analyzed how
      aneuploidy is linked to intratumor heterogeneity. In our cohort, none of the
      patients with diploid tumors died of breast cancer during follow-up in contrast
      to four of six patients with aneuploid tumors (mean survival 86.4 months). The
      FISH analysis showed markedly increased genomic instability and intratumor
      heterogeneity in aneuploid tumors. MYC gain was observed in only 20% of the
      diploid cancers, while all aneuploid cases showed a gain. The mutation burden was
      similar in diploid and aneuploid tumors, however, TP53 mutations were not
      observed in diploid tumors, but in all aneuploid tumors in our collective. We
      conclude that quantitative measurements of intratumor heterogeneity by multiplex
      FISH, detection of MYC amplification and TP53 mutation could augment
      prognostication in breast cancer patients.

PMID- 29181862
TI  - Perforation and right ventricular outflow tract stenting: Alternative palliation
      for infants with pulmonary atresia/ventricular septal defect.
AB  - BACKGROUND: Right ventricular outflow tract (RVOT) stents have been used as
      palliation in patients with severe tetralogy of Fallot (TOF). Radiofrequency
      perforation of the RVOT has also been described in patients with pulmonary
      atresia (PA)/ventricular septal defect (VSD). However, RVOT stenting in
      conjunction with radiofrequency perforation as a means for establishing reliable
      pulmonary blood flow in patients with PA/VSD has not previously been reported.
      OBJECTIVES: Our aim is to report our experience with using perforation of plate
      like pulmonary valve atresia combined with stenting of RVOT as an alternative and
      equally efficacious intervention for infants with PA/VSD, as compared to a
      surgical pulmonary artery shunt (SPS). METHODS: A retrospective review of
      patients with PA/VSD at our institution from Jan 2006 to October 2015 was
      performed. RESULTS: Twenty-seven patients received palliation for PA/VSD. Five
      (median 2.5 kg, 2.1-4.1 kg) underwent RVOT stenting and 22 (3.5 kg, 2.1-4.6 kg)
      underwent surgical SPS. Of the patients who received an RVOT stent, 3 underwent
      guidewire perforation and balloon dilation of the plate-like pulmonary valve, and
      2 underwent radiofrequency perforation of the pulmonary plate, followed by
      balloon dilation. Postprocedure saturations averaged 93% in the stent group and
      89% in the shunt group. One of the patients who underwent RVOT stenting required
      additional stenting of the PDA for isolation of the LPA, but none required re
      intervention. Four patients in the SPS cohort required re-intervention (18%). Two
      required stenting of the shunt, and 2 required surgical revision of the shunt.
      There was one death in the stent group, however this was secondary to withdrawal
      of support given an underlying genetic diagnosis (trisomy 13). There was one
      fatality in the SPS cohort prior to hospital discharge. CONCLUSIONS: Perforation
      followed by RVOT stenting may be a safe and effective alternative to surgical SPS
      in infants with PA/VSD.

PMID- 29181864
TI  - Functions of the multi-interacting protein KIDINS220/ARMS in cancer and other
      pathologies.
AB  - Development of an organ and subsequently the whole system from an embryo is a
      highly integrated process. Although there is evidence that different systems are
      interconnected during developmental stages, the molecular understanding of this
      relationship is either not known or only to a limited extent. Nervous system
      development, amongst all, is maybe the most crucial and complex process. It
      relies on the correct distribution of specific neuronal growth factors and
      hormones to the specific receptors. Among the plethora of proteins that are
      involved in downstream signalling of neuronal growth factors, we find the kinase
      D interacting substrate of 220 kDa (KIDINS220), also known as ankyrin-rich repeat
      membrane spanning (ARMS) protein. KIDINS220 has been shown to play a substantial
      role in the nervous system and vascular system development as well as in neuronal
      survival and differentiation. It serves as a downstream regulator for many
      important neuronal and vascular growth factors such as vascular endothelial
      growth factor (VEGF), the neurotrophin family, glutamate receptors and ephrin
      receptors. Moreover, activation and differentiation of B- and T-cells, as well as
      tumour cell proliferation has also shown to be related to KIDINS220. This review
      comprehensively summarises the existing research data on this protein, with a
      particular interest in its role in cancer and in other pathologies.

PMID- 29181863
TI  - Confined Carbon Mediating Dehydroaromatization of Methane over Mo/ZSM-5.
AB  - Non-oxidative dehydroaromatization of methane (MDA) is a promising catalytic
      process for direct valorization of natural gas to liquid hydrocarbons. The
      application of this reaction in practical technology is hindered by a lack of
      understanding about the mechanism and nature of the active sites in benchmark
      zeolite-based Mo/ZSM-5 catalysts, which precludes the solution of problems such
      as rapid catalyst deactivation. By applying spectroscopy and microscopy, it is
      shown that the active centers in Mo/ZSM-5 are partially reduced single-atom Mo
      sites stabilized by the zeolite framework. By combining a pulse reaction
      technique with isotope labeling of methane, MDA is shown to be governed by a
      hydrocarbon pool mechanism in which benzene is derived from secondary reactions
      of confined polyaromatic carbon species with the initial products of methane
      activation.

PMID- 29181865
TI  - A pi-Conjugation Extended Viologen as a Two-Electron Storage Anolyte for Total
      Organic Aqueous Redox Flow Batteries.
AB  - Extending the conjugation of viologen by a planar thiazolo[5,4-d]thiazole (TTz)
      framework and functionalizing the pyridinium with hydrophilic ammonium groups
      yielded a highly water-soluble pi-conjugation extended viologen, 4,4'
      (thiazolo[5,4-d]thiazole-2,5-diyl)bis(1-(3-(trimethylammonio)propyl)pyridin-1
      ium) tetrachloride, [(NPr)2 TTz]Cl4  , as a novel two-electron storage anolyte
      for aqueous organic redox flow battery (AORFB) applications. Its physical and
      electrochemical properties were systematically investigated. Paired with 4
      trimethylammonium-TEMPO (NMe -TEMPO) as catholyte, [(NPr)2 TTz]Cl4 enables a 1.44
      V AORFB with a theoretical energy density of 53.7 Wh L-1 . A demonstrated [(NPr)2
      TTz]Cl4 /NMe -TEMPO AORFB delivered an energy efficiency of 70 % and 99.97 %
      capacity retention per cycle.

PMID- 29181866
TI  - 'Last In-First Out': seasonal variations of non-structural carbohydrates, glucose
      6-phosphate and ATP in tubers of two Arum species.
AB  - Knowledge on the metabolism of polysaccharide reserves in wild species is still
      scarce. In natural sites we collected tubers of Arum italicum Mill. and A.
      maculatum L. - two geophytes with different apparent phenological timing, ecology
      and chorology - during five stages of the annual cycle in order to understand
      patterns of reserve accumulation and degradation. Both the entire tuber and its
      proximal and distal to shoot portion were utilised. Pools of non-structural
      carbohydrates (glucose, sucrose and starch), glucose-6-phosphate and ATP were
      analysed as important markers of carbohydrate metabolism. In both species, starch
      and glucose content of the whole tuber significantly increased from sprouting to
      the maturation/senescence stages, whereas sucrose showed an opposite trend; ATP
      and glucose-6-phosphate were almost stable and dropped only at the end of the
      annual cycle. Considering the two different portions of the tuber, both ATP and
      glucose-6-phosphate concentrations were higher in proximity to the shoot in all
      seasonal stages, except the flowering stage. Our findings suggest that seasonal
      carbon partitioning in the underground organ is driven by phenology and occurs
      independently of seasonal climate conditions. Moreover, our results show that
      starch degradation, sustained by elevated ATP and glucose-6-phosphate pools,
      starts in the peripheral, proximal-to-shoot portion of the tuber, consuming
      starch accumulated in the previous season, as a 'Last In-First Out' mechanism of
      carbohydrate storage.

PMID- 29181867
TI  - Ultrathin Graphdiyne Nanosheets Grown In Situ on Copper Nanowires and Their
      Performance as Lithium-Ion Battery Anodes.
AB  - A method is presented for the scalable preparation of high-quality graphdiyne
      nanotubes and ultrathin graphdiyne nanosheets (average thickness: ca. 1.9 nm)
      using Cu nanowires as a catalyst. For the storage of Li+ ions, the graphdiyne
      nanostructures show a high capacity of 1388 mAh g-1 and high rate performance
      (870 mA h g-1 at 10 A g-1 , and 449.8 mA h g-1 at 20 A g-1 ) with robust
      stability, demonstrating outstanding overall potential for its applications.

PMID- 29181868
TI  - Low molecular weight heparin as an anticoagulation strategy for left-sided
      ablation procedures.
AB  - OBJECTIVE: This quality improvement study was implemented to demonstrate
      consistent and reliable post procedure anticoagulation for patients undergoing
      left-sided ablations. We evaluated the safety and efficacy of anticoagulation
      practice during a transition from anticoagulation with overnight infusion of
      unfractionated heparin to a single subcutaneous injection of low molecular weight
      heparin. METHODS: Outcomes for patients who received unfractionated heparin from
      January 2014 to October 2014, were compared with outcomes of patients who
      received low molecular weight heparin from October 2014 to October 2015.
      Complications prepractice and postpractice change were documented and compared to
      establish confidence in the practice change and confirm the safety of the
      anticoagulation therapy management. RESULTS: There were no differences in the
      type or frequency of complications/adverse events demonstrated between the
      patients who had received unfractionated heparin for anticoagulation prophylaxis
      and those who received low molecular weight heparin. No thromboembolic events
      were reported or documented with either anticoagulation strategy. After
      confidence in the safety and efficacy of the practice change was established, a
      decision was made to discharge patients home the same day as there procedure,
      effectively reducing inpatient bed days and overall costs. CONCLUSION:
      Administration of low molecular weight heparin provides predictable
      anticoagulation and equally safe as unfractionated heparin when administered to
      patients post left-sided ablation. A secondary gain has been reduction of
      procedural costs by elimination of the previously required inpatient observation
      stay.

PMID- 29181869
TI  - Sample size re-estimation incorporating prior information on a nuisance
      parameter.
AB  - Prior information is often incorporated informally when planning a clinical
      trial. Here, we present an approach on how to incorporate prior information, such
      as data from historical clinical trials, into the nuisance parameter-based sample
      size re-estimation in a design with an internal pilot study. We focus on trials
      with continuous endpoints in which the outcome variance is the nuisance
      parameter. For planning and analyzing the trial, frequentist methods are
      considered. Moreover, the external information on the variance is summarized by
      the Bayesian meta-analytic-predictive approach. To incorporate external
      information into the sample size re-estimation, we propose to update the meta
      analytic-predictive prior based on the results of the internal pilot study and to
      re-estimate the sample size using an estimator from the posterior. By means of a
      simulation study, we compare the operating characteristics such as power and
      sample size distribution of the proposed procedure with the traditional sample
      size re-estimation approach that uses the pooled variance estimator. The
      simulation study shows that, if no prior-data conflict is present, incorporating
      external information into the sample size re-estimation improves the operating
      characteristics compared to the traditional approach. In the case of a prior-data
      conflict, that is, when the variance of the ongoing clinical trial is unequal to
      the prior location, the performance of the traditional sample size re-estimation
      procedure is in general superior, even when the prior information is robustified.
      When considering to include prior information in sample size re-estimation, the
      potential gains should be balanced against the risks.

PMID- 29181870
TI  - Lithium-Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols:
      Synthesis of 3-Sulfanyl-Oxetanes as Bioisosteres.
AB  - 3-Sulfanyl-oxetanes are presented as promising novel bioisosteric replacements
      for thioesters or benzyl sulfides. From oxetan-3-ols, a mild and inexpensive Li
      catalyst enables chemoselective C-OH activation and thiol alkylation. Oxetane
      sulfides are formed from various thiols providing novel motifs in new chemical
      space and specifically as bioisosteres for thioesters due to their similar shape
      and electronic properties. Under the same conditions, various pi-activated
      secondary and tertiary alcohols are also successful. Derivatization of the
      oxetane sulfide linker provides further novel oxetane classes and building
      blocks. Comparisons of key physicochemical properties of the oxetane compounds to
      selected carbonyl and methylene analogues indicate that these motifs are suitable
      for incorporation into drug discovery efforts.

PMID- 29181871
TI  - Outcome of 9 dogs treated with stereotactic radiation therapy for primary or
      metastatic vertebral osteosarcoma.
AB  - Primary and metastatic vertebral osteosarcoma (OSA) in the dog carries an overall
      guarded prognosis. Previously reported definitive treatments in dogs with
      vertebral OSA have included surgery, radiotherapy, chemotherapy or a combination
      of those therapies. This retrospective study was completed to determine patterns
      of failure, duration of local control and survival time in dogs with vertebral
      OSA treated with stereotactic radiation therapy (SRT). Nine dogs were treated
      with SRT for vertebral OSA. Protocols ranged from 1 to 5 fractions with total
      prescription ranging from 13.5 to 36 Gy. Six dogs had primary lesions and 3 had
      metastatic lesions. Neurologic score improved in 4 patients, remained the same in
      4 and worsened in 1. Five of the 6 dogs that presented with assessable spinal
      pain had reported improvement in pain. Overall median survival time was 139 days
      and median duration of pain control was 77 days. There was not a statistically
      significant survival difference between dogs presenting with primary or
      metastatic disease, or dogs that had improvement in neurologic score following
      SRT. The data suggests similar survival times to the previously reported
      definitive treatments in dogs with vertebral OSA and displays continued
      difficulty in controlling this tumour. The dose limiting structure is the late
      responding spinal cord, but many of the patients herein died prior to the
      expected time to development of late radiation side effects.

PMID- 29181872
TI  - Validation of T1w-based segmentations of white matter hyperintensity volumes in
      large-scale datasets of aging.
AB  - INTRODUCTION: Fluid-attenuated Inversion Recovery (FLAIR) and dual T2w and proton
      density (PD) magnetic resonance images (MRIs) are considered to be the optimum
      sequences for detecting white matter hyperintensities (WMHs) in aging and
      Alzheimer's disease populations. However, many existing large multisite studies
      forgo their acquisition in favor of other MRI sequences due to economic and time
      constraints. METHODS: In this article, we have investigated whether FLAIR and
      T2w/PD sequences are necessary to detect WMHs in Alzheimer's and aging studies,
      compared to using only T1w images. Using a previously validated automated tool
      based on a Random Forests classifier, WMHs were segmented for the baseline visits
      of subjects from ADC, ADNI1, and ADNI2/GO studies with and without T2w/PD and
      FLAIR information. The obtained WMH loads (WMHLs) in different lobes were then
      correlated with manually segmented WMHLs, each other, age, cognitive, and
      clinical measures to assess the strength of the correlations with and without
      using T2w/PD and FLAIR information. RESULTS: The WMHLs obtained from T1w-Only
      segmentations correlated with the manual WMHLs (ADNI1: r = .743, p < .001,
      ADNI2/GO: r = .904, p < .001), segmentations obtained from T1w + T2w + PD for
      ADNI1 (r = .888, p < .001) and T1w + FLAIR for ADNI2/GO (r = .969, p < .001), age
      (ADNI1: r = .391, p < .001, ADNI2/GO: r = .466, p < .001), and ADAS13 (ADNI1: r =
      .227, p < .001, ADNI2/GO: r = .190, p < 0.001), and NPI (ADNI1: r = .290, p <
      .001, ADNI2/GO: r = 0.144, p < .001), controlling for age. CONCLUSION: Our
      results suggest that while T2w/PD and FLAIR provide more accurate estimates of
      the true WMHLs, T1w-Only segmentations can still provide estimates that hold
      strong correlations with the actual WMHLs, age, and performance on various
      cognitive/clinical scales, giving added value to datasets where T2w/PD or FLAIR
      are not available.

PMID- 29181873
TI  - Lambl's excrescences in children: Improved detection via transthoracic
      echocardiography.
AB  - BACKGROUND: Lambl's excrescences (LE) are fibrous extensions that can be found
      along the lines of closure of the aortic valve. Due to improvements in ultrasound
      technology, LE are frequently imaged during transthoracic echocardiography (TTE)
      in adults. OBJECTIVE: The purpose of this study was to determine the prevalence
      of LE among children from two eras (2004-2006 and 2011-2012) and the effect of
      technological advancements on LE detection. METHODS: TTE from 700 subjects (age
      18 years old or younger) were reviewed. All parasternal long and short axis
      images of the aortic valve were reviewed by a board certified echocardiographer,
      and the positive studies were then reviewed by two additional observers to
      confirm the presence of LE. A two-sample t test with 95% significance was used to
      analyze the presence of LE in the cohorts. Median follow-up duration was 66
      months. RESULTS: Of the 700 subjects, 12 (1.7%) children were found to have LE.
      No significant difference in prevalence was found between the two eras (.9% vs.
      2.6%, P = .08) and the presence of LE was not related to age (P = .36). The
      youngest subject with an LE was 5 months old. During long-term follow-up there
      were no clinical events in the 12 children identified with a LE. CONCLUSIONS: The
      prevalence of LE in children is lower than that reported in adults, this supports
      the age-related "wear and tear" process that has been described in previous
      studies. LE do not require intervention or more aggressive invasive imaging in
      children.

PMID- 29181874
TI  - Using a statewide survey methodology to prioritize pediatric cardiology core
      content.
AB  - OBJECTIVE: Although pediatrician-reported relevance of Canadian cardiology
      specific objectives has been studied, similar data are not available for the 2016
      American Board of Pediatrics (ABP) cardiology-specific objectives. This study
      asked Kentucky trainees, pediatricians, and pediatric cardiologists to identify
      "most important" content within these objectives. DESIGN, METHODS, OUTCOME
      MEASURES: This cross-sectional study used an original, online survey instrument
      based on the 2016 ABP cardiology-specific objectives. We collected quantitative
      data (numerical indications of importance) and qualitative data (open-ended
      replies regarding missing content and difficulty in teaching and learning).
      Respondents indicated the top two choices of most important items within eight
      content areas. Descriptive statistics (frequencies and percentages) and chi
      square analysis were calculated. Content within categories was organized using
      naturally occurring "clusters" and "gaps" in scores. Common themes among open
      ended qualitative responses were identified using Pandit's version of Glaser and
      Strauss Grounded theory (constant comparison). RESULTS: Of the 136 respondents,
      23 (17%) were residents, 15 (11%) fellows, 85 (62%) pediatricians, and 13 (10%)
      pediatric cardiologists. Of attendings, 80% reported faculty/gratis faculty
      status. Naturally occurring clusters in respondent-designated importance resulted
      in <=3 "most selected" objectives per content area. Objectives in "most selected"
      content pertained to initial diagnosis (recognition of abnormality/disease) (n =
      16), possible emergent/urgent intervention required (n = 14), building a
      differential (n = 8), and planning a workup (n = 4). Conversely, themes for
      "least selected" content included comanagement with subspecialist (n = 15),
      knowledge useful in patient-family communication (n = 9), knowledge that can be
      referenced (as needed) (n = 7), and longitudinal/follow-up concerns (n = 5).
      CONCLUSIONS: This study demonstrated the utility of an online survey methodology
      to identify pediatric cardiology content perceived most important. Learners and
      faculty generally provided concordant responses regarding most important content
      within the cardiology-specific ABP objectives. Medical educators could apply this
      methodology to inform curriculum revision.

PMID- 29181875
TI  - Integration of routine QA data into mega-analysis may improve quality and
      sensitivity of multisite diffusion tensor imaging studies.
AB  - A novel mega-analytical approach that reduced methodological variance was
      evaluated using a multisite diffusion tensor imaging (DTI) fractional anisotropy
      (FA) data by comparing white matter integrity in people with schizophrenia to
      controls. Methodological variance was reduced through regression of variance
      captured from quality assurance (QA) and by using Marchenko-Pastur Principal
      Component Analysis (MP-PCA) denoising. N = 192 (119 patients/73 controls) data
      sets were collected at three sites equipped with 3T MRI systems: GE MR750, GE
      HDx, and Siemens Trio. DTI protocol included five b = 0 and 60 diffusion
      sensitized gradient directions (b = 1,000 s/mm2 ). In-house DTI QA protocol data
      was acquired weekly using a uniform phantom; factor analysis was used to distil
      into two orthogonal QA factors related to: SNR and FA. They were used as site
      specific covariates to perform mega-analytic data aggregation. The effect size of
      patient-control differences was compared to these reported by the enhancing neuro
      imaging genetics meta-analysis (ENIGMA) consortium before and after regressing QA
      variance. Impact of MP-PCA filtering was evaluated likewise. QA-factors explained
      ~3-4% variance in the whole-brain average FA values per site. Regression of QA
      factors improved the effect size of schizophrenia on whole brain average FA
      values-from Cohen's d = .53 to .57-and improved the agreement between the
      regional pattern of FA differences observed in this study versus ENIGMA from r =
      .54 to .70. Application of MP-PCA-denoising further improved the agreement to r =
      .81. Regression of methodological variances captured by routine QA and advanced
      denoising that led to a better agreement with a large mega-analytic study.

PMID- 29181877
TI  - Formal and informal care for community-dwelling frail elderly people over time: A
      comparison of integrated and usual care in the Netherlands.
AB  - : While integration has become a central tenet of community-based care for frail
      elderly people, little is known about its impact on formal and informal care and
      their dynamics over time. The aim of this study was therefore to examine how an
      integrated care intervention for community-dwelling frail elderly people affects
      the amount and type of formal and informal care over 12 months as compared to
      usual care. A quasi-experimental design with a control group was used. Data
      regarding formal and informal care were collected from frail elderly patients (n
      = 207) and informal caregivers (n = 74) with pre/post-questionnaires. Within- and
      between-group comparisons and multiple linear regression analyses were performed.
      The results showed marginal changes over time in the amount of formal and
      informal care in both integrated care and usual care. However, different
      associations between changes in formal and informal care were found in integrated
      and usual care. Most notably, informal caregivers provided more instrumental
      assistance over time if formal caregivers provided less personal care (and vice
      versa) in integrated care but not in usual care. These results suggest that
      integrated care does not necessarily change the contribution of formal or
      informal care, but changes the interaction between formal (personal care) and
      informal (instrumental) activities. Implications and recommendations for research
      and practice are discussed. TRIAL REGISTRATION: Current Controlled Trials
      ISRNT05748494.

PMID- 29181876
TI  - Coumarin enhances nitrate uptake in maize roots through modulation of plasma
      membrane H+ -ATPase activity.
AB  - Coumarin is one of the simplest plant secondary metabolites, widely distributed
      in the plant kingdom, affecting root form and function, including anatomy,
      morphology and nutrient uptake. Although, some plant responses to coumarin have
      been described, comprehensive knowledge of the physiological and molecular
      mechanisms is lacking. Maize seedlings exposed to different coumarin
      concentrations, alone or in combination with 200 MUm nitrate (NO3- ), were
      analysed, through a physiological and molecular approach, to elucidate action of
      coumarin on net NO3- uptake rate (NNUR). In detail, the time course of NNUR,
      plasma membrane (PM) H+ -ATPase activity, proton pumping and related gene
      expression (ZmNPF6.3, ZmNRT2.1, ZmNAR2.1, ZmHA3 and ZmHA4) were evaluated.
      Coumarin alone did not affect nitrate uptake, PM H+ -ATPase activity or
      transcript levels of ZmNRT2.1 and ZmHA3. In contrast, coumarin alone increased
      ZmNPF6.3, ZmNAR2.1 and ZmHA4 expression in response to abiotic stress. When
      coumarin and NO3- were concurrently added to the nutrient solution, a significant
      increase in the NNUR, PM H+ -ATPase activity, together with ZmNAR2.1:ZmNRT2.1 and
      ZmHA4 expression was observed, suggesting that coumarin affected the inducible
      component of the high affinity transport system (iHATS), and this effect appeared
      to be mediated by nitrate. Moreover, results with vanadate, an inhibitor of the
      PM H+ -ATPase, suggested that this enzyme could be the main target of coumarin.
      Surprisingly, coumarin did not affect PM H+ -ATPase activity by direct contact
      with plasma membrane vesicles isolated from maize roots, indicating its possible
      elicitor role in gene transcription.

PMID- 29181878
TI  - Linear and Nonlinear Optical Properties of Tricyanopropylidene-Based Merocyanine
      Dyes: Synergistic Experimental and Theoretical Investigations.
AB  - New merocyanines dyes with tricyanopropylidene-based acceptor units connected to
      dihexylaminophenyl or dihexylaminothiophenyl donor moieties through polyenic
      bridges of different lengths have been designed. All derivatives exhibited a
      strong dipolar character and showed a typical intramolecular charge transfer
      (ICT) transition. NMR spectroscopy experiments combined with DFT calculations
      demonstrated that both the nature of the donor-acceptor pair and the length of
      the conjugated linker strongly impact the electronic structure of the dyes and
      induce alteration in the bond-length alternation (BLA) and marked shifts in the
      ICT absorption bands. Hyper-Rayleigh scattering experiments revealed an
      exponential increase in the second-harmonic generation response as the polyenic
      chain length was increased. Strikingly, the largest chromophores with the
      strongest donor-acceptor pair exhibited a very high first hyperpolarizabilty
      together with a cyanine-like electronic structure, which apparently contradicts
      the paradigm of optimal BLA predicted by the two-state model. Although it
      decreased as the polyenic chain length increased, all dyes also exhibited high
      thermal stability, which demonstrates their potential for applications in
      nonlinear optical devices.

PMID- 29181880
TI  - Histological evaluations and inflammatory responses of different dental implant
      abutment materials: A human histology pilot study.
AB  - BACKGROUND: Improvements of soft tissue to the abutment surface results in more
      stable peri-implant conditions, however, few human histological studies have
      compared soft tissue responses around different abutment materials. PURPOSE: To
      describe the peri-implant tissue around 3 abutment materials; titanium, zirconia,
      and gold alloy, over an 8-week healing period. MATERIALS AND METHODS: Fifteen
      edentulous sites were treated with implants. Eight weeks later, peri-implant
      tissue was harvested and processed using a nonseparation resin embedded
      technique. The tissue attachment characteristics were assessed at clinical stages
      using the gingival index (GI) score, surgical stage (surgical score), and
      histological stage (histological attachment percentage). Additionally, the
      inflammatory responses were evaluated using inflammatory extent and inflammatory
      cellularity grades. Nonparametrical statistics were used to describe the GI and
      surgical scores, and analytical statistics were used to analyze the histological
      attachment percentages as well as the inflammatory extent and cellularity grades
      amongst the 3 groups. RESULTS: There were no statistically significant
      differences among the groups for GI score (P = .071) and surgical score (P =
      .262). Titanium and zirconia exhibited nearly similar mean histological
      attachment percentages while gold alloy had a significantly lower percentage (P =
      .004). For the inflammatory extent and cellularity grades, the odds of being one
      grade higher for gold alloy abutment was 5.18 and 17.8 times that of titanium
      abutment, respectively. However, for the zirconia abutment, the odds were 0.87
      and 7.5 times higher than the titanium group. CONCLUSIONS: The tissue around the
      gold alloy abutments resulted in worse attachment conditions compared with the
      titanium and zirconia abutments. Inflammation tended to be higher in the tissue
      around the gold alloy abutments than the titanium and zirconia abutments.

PMID- 29181879
TI  - High human herpesvirus 6 viral load in pediatric allogeneic hematopoietic stem
      cell transplant patients is associated with detection in end organs and high
      mortality.
AB  - Human Herpes Virus 6 (HHV-6) reactivation occurs in approximately half of
      patients following allogeneic hematopoietic stem cell transplant (HSCT). While
      encephalitis and delayed engraftment are well-documented complications of HHV-6
      following HSCT, the extent to which HHV-6 viremia causes disease in children is
      controversial. We performed a retrospective review of HHV-6 reactivation and
      possible manifestations in pediatric allogeneic HSCT patients at a single
      institution. Of 89 children and young adults who underwent allogeneic HSCT over a
      three-and-a-half-year period, 34 patients reactivated HHV-6 early post
      transplant. Unrelated donor stem cell source and lack of antiviral prophylaxis
      were risk factors for the development of HHV-6 viremia. Viremia correlated with
      the presence of acute graft-versus-host disease, but not chronic graft-versus
      host disease. We identified two subgroups within the viremic patients-a high-risk
      viremic and tissue-positive group that reactivated HHV-6 and had suspected end
      organ disease and a low-risk viremic but asymptomatic group that reactivated HHV
      6 but did not exhibit symptoms or signs of end-organ disease. Peak viral load was
      found to be strongly associated with mortality. Prospective studies in larger
      numbers of patients are needed to further investigate the role of HHV-6 in
      causing symptomatic end-organ disease as well as the association of viral load
      with mortality.

PMID- 29181881
TI  - Effects of triclosan on Japanese medaka (Oryzias latipes) during embryo
      development, early life stage and reproduction.
AB  - Triclosan has been shown to have endocrine-disrupting effects in aquatic
      organisms. In 2016, the US Food and Drug Administration banned the use of
      triclosan in consumer soaps. Before the ban, triclosan was reported at low
      concentrations in the aquatic environment, although the effect of triclosan on
      reproduction in teleost fish species is yet to be clarified. Here we investigated
      the effects of triclosan on embryo development and reproduction, and during the
      early life stage, in Japanese medaka (Oryzias latipes) by using Organisation for
      Economic Co-operation and Development tests 229, 212 and 210, with minor
      modifications. In adult medaka, exposure to 345.7 MUg l-1 suppressed fecundity
      and increased mortality but had no effect on fertility. Exposure to 174.1 or
      345.7 MUg l-1 increased liver vitellogenin concentration in females but decreased
      liver vitellogenin concentration in males. With triclosan exposure, mortality was
      increased dose dependently during the embryonic and early larval stages, and a
      particularly steep increase in mortality was observed soon after hatching. The
      lowest observed effect concentrations of triclosan in Japanese medaka obtained in
      the present study (mortality [embryonic and larval stages, 276.3 MUg l-1 ; early
      life stage, 134.4 MUg l-1 ; adult stage, 174.1 MUg l-1 ], growth [134.4 MUg l-1
      ], vitellogenin [174.1 MUg l-1 ], fecundity [345.7 MUg l-1 ] and fertility
      [>345.7 MUg l-1 ]) were at least 55 times (compared with the USA) and up to 13
      400 times (compared with Germany) greater than the detected triclosan levels in
      the aquatic environment. These results suggest that triclosan may not be
      affecting fish populations in the aquatic environment.

PMID- 29181882
TI  - Heparin-induced thrombocytopenia complicating children after the Fontan
      procedure: Single-center experience and review of the literature.
AB  - Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of
      heparin therapy. The risk for HIT correlates with the cumulative dosage of
      heparin exposure. In Fontan patients, recurrent systemic anticoagulation,
      traditionally with heparin, is used to alleviate the thrombotic complications
      that may occur postoperatively when the venous pressure rises and the systemic
      venous flow into the pulmonary arteries becomes sluggish, putting them at
      increased risk. As a pressure gradient-dependent circulation, elevation in
      systemic venous pressure, most often by venous thrombosis, contributes to circuit
      failure. Therefore, when HIT complicates patients after the Fontan procedure, it
      is associated with a high thrombotic morbidity and mortality; thus, a high index
      of suspicion is mandatory, based on the clinical signs of HIT. It is crucial to
      intervene early with alternative anticoagulants when HIT is suspected as this
      step may improve outcome in these patients.

PMID- 29181883
TI  - Real-time fMRI neurofeedback of the mediodorsal and anterior thalamus enhances
      correlation between thalamic BOLD activity and alpha EEG rhythm.
AB  - Real-time fMRI neurofeedback (rtfMRI-nf) with simultaneous EEG allows volitional
      modulation of BOLD activity of target brain regions and investigation of related
      electrophysiological activity. We applied this approach to study correlations
      between thalamic BOLD activity and alpha EEG rhythm. Healthy volunteers in the
      experimental group (EG, n = 15) learned to upregulate BOLD activity of the target
      region consisting of the mediodorsal (MD) and anterior (AN) thalamic nuclei using
      rtfMRI-nf during retrieval of happy autobiographical memories. Healthy subjects
      in the control group (CG, n = 14) were provided with a sham feedback. The EG
      participants were able to significantly increase BOLD activities of the MD and
      AN. Functional connectivity between the MD and the inferior precuneus was
      significantly enhanced during the rtfMRI-nf task. Average individual changes in
      the occipital alpha EEG power significantly correlated with the average MD BOLD
      activity levels for the EG. Temporal correlations between the occipital alpha EEG
      power and BOLD activities of the MD and AN were significantly enhanced, during
      the rtfMRI-nf task, for the EG compared to the CG. Temporal correlations with the
      alpha power were also significantly enhanced for the posterior nodes of the
      default mode network, including the precuneus/posterior cingulate, and for the
      dorsal striatum. Our findings suggest that the temporal correlation between the
      MD BOLD activity and posterior alpha EEG power is modulated by the interaction
      between the MD and the inferior precuneus, reflected in their functional
      connectivity. Our results demonstrate the potential of the rtfMRI-nf with
      simultaneous EEG for noninvasive neuromodulation studies of human brain function.

PMID- 29181884
TI  - miR-221/222 cluster expression improves clinical stratification of non-muscle
      invasive bladder cancer (TaT1) patients' risk for short-term relapse and
      progression.
AB  - Clinical heterogeneity of bladder cancer prognosis requires the identification of
      bladder tumors' molecular profile to improve the prediction value of the
      established and clinically used markers. In this study, we have analyzed miR
      221/222 cluster expression in bladder tumors and its clinical significance for
      patients' prognosis and disease outcome. The study included 387 tissue specimens.
      Following extraction, total RNA was polyadenylated at 3'-end and reversed
      transcribed. SYBR-Green based qPCR assays were performed for the quantification
      of miR-221/222 expression. Extensive statistical analysis was completed for the
      evaluation of miR-221/222 cluster's clinical significance. The expression of miR
      221/222 is significantly downregulated in tumors compared to normal urothelium,
      while ROC curve and logistic regression analysis highlighted cluster's
      discriminatory ability. However, miR-222 levels were increased in muscle-invasive
      (T2-T4) compared to superficial tumors (TaT1), and in high compared to low-grade
      tumors. Kaplan-Meier survival curves and Cox regression analysis revealed the
      stronger risk of TaT1 patients overexpressing miR-222 for disease short-term
      relapse and progression following treatment. Moreover, multivariate Cox models
      highlighted the independent prognostic value of miR-222 overexpression for TaT1
      patients' poor prognosis. Finally, the analysis of miR-222 expression improved
      significantly the positive prediction strength of the clinically used prognostic
      markers of tumor stage, grade, EORTC risk-stratification and recurrence at the
      first follow-up cystoscopy for TaT1 patients' outcome, and resulted to higher
      clinical net benefit following decision curve analysis. In conclusion, the
      expression of miR-221/222 cluster is deregulated in bladder tumors and miR-222
      overexpression results to a superior positive prediction of TaT1 patients' short
      term relapse and progression.

PMID- 29181885
TI  - Exploring PTDH-P450BM3 Variants for the Synthesis of Drug Metabolites.
AB  - The conversion of a series of pharmaceutical compounds was examined with three
      variants of cytochrome P450BM3 fused to phosphite dehydrogenase (PTDH) to enable
      cofactor recycling. Conditions for enzyme production were optimized, and the
      purified PTDH-P450BM3 variants were tested against 32 commercial drugs by using
      rapid UPLC-MS analysis. The sets of mutations (R47L/F87V/L188Q and
      R47L/F87V/L188Q/E267V/G415S) improved conversion for all compounds, and a variety
      of products were detected. Product analysis showed that reaction types included C
      hydroxylation, N-oxidation, demethylation, and aromatization. Interestingly,
      enzymatic aromatization could occur independent of the addition of reducing
      coenzyme. These results identified new conversions catalyzed by P450BM3 variants
      and showed that a small set of mutations in the oxygenase domain could broaden
      both substrate range and reaction type.

PMID- 29181886
TI  - Salmonella in breeding pigs: Shedding pattern, transmission of infection and the
      role of environmental contamination in Irish commercial farrow-to-finish herds.
AB  - This study aimed to provide new insights into the epidemiology of Salmonella in
      pig production, focusing on potential shedding patterns in breeding pigs
      throughout a full production cycle and the risk of transmission of infection from
      the sow to her offspring. A longitudinal study was conducted on five farrow-to
      finish commercial pig farms. In each herd, shedding of Salmonella in faeces was
      monitored in breeders through service, gestation and lactation. Swabs of the
      farrowing room floor and pools of faeces from piglets were collected on two
      occasions during lactation. Environmental pen swabs were also taken in the
      weaning and finisher houses. Salmonella isolates were serotyped, tested for
      antimicrobial resistance (AMR) and typed by Multiple-Locus Variable number tandem
      repeat Analysis (MLVA). Shedding by breeding pigs was low in all stages of the
      production cycle; 5% of sows shed at service, the production stage with highest
      risk of shedding (p < .01), 1.6% shed during gestation and 2.5% after farrowing.
      Salmonella was detected in 4% of piglet faecal pools in the second week post
      farrowing and 5% in the fourth week. Serotyping and AMR profiles of Salmonella
      isolates revealed that strains in sows and gilts were mostly different from
      strains isolated in weaner and finisher facilities. MLVA typing confirmed that
      the source of infection in piglets was in most instances the contaminated
      environment rather than their dam. Based on the typing results, it appears that
      sows do not pose a major risk in the maintenance and transmission of Salmonella
      to their progeny but instead the contaminated pen environment is more significant
      in the perpetuation of the organism on farm.

PMID- 29181887
TI  - Historic and geographic surveillance of Pseudogymnoascus destructans possible
      from collections of bat parasites.
AB  - Specimens archived in wet collections represent valuable material for scientific
      research. Here, we show that bat fly (Diptera, Nycteribiidae) samples contain DNA
      of Pseudogymnoascus destructans, a fungus pathogenic to bats. Using dual-probe
      quantitative PCR, we detected P. destructans DNA on bat flies collected in the
      Samara, Sverdlovsk and Irkutsk regions of Russia between 2005 and 2017. Fungal
      load was significantly lower on bat flies from wet collections than on freshly
      collected mites in the Czech Republic. The bat pathogen was present in the Samara
      region (European part of Russia) in 2005, that is, a year before recognition of
      white-nose syndrome in North America. As Samara and Irkutsk regions were
      identified as new positive locations of P. destructans, our data expand the known
      geographic distribution of P. destructans. We conclude that ethanol-stored
      ectoparasites can be used to identify the presence of pathogens in historic bat
      populations and understudied geographical regions.

PMID- 29181889
TI  - 6th Meeting of the COMET Initiative (VI), Amsterdam, November 10-11 2016.

PMID- 29181888
TI  - Preconditioned augmented Lagrangian formulation for nearly incompressible cardiac
      mechanics.
AB  - Computational modeling of the heart is a subject of substantial medical and
      scientific interest, which may contribute to increase the understanding of
      several phenomena associated with cardiac physiological and pathological states.
      Modeling the mechanics of the heart have led to considerable insights, but it
      still represents a complex and a demanding computational problem, especially in a
      strongly coupled electromechanical setting. Passive cardiac tissue is commonly
      modeled as hyperelastic and is characterized by quasi-incompressible,
      orthotropic, and nonlinear material behavior. These factors are known to be very
      challenging for the numerical solution of the model. The near-incompressibility
      is known to cause numerical issues such as the well-known locking phenomenon and
      ill-conditioning of the stiffness matrix. In this work, the augmented Lagrangian
      method is used to handle the nearly incompressible condition. This approach can
      potentially improve computational performance by reducing the condition number of
      the stiffness matrix and thereby improving the convergence of iterative solvers.
      We also improve the performance of iterative solvers by the use of an algebraic
      multigrid preconditioner. Numerical results of the augmented Lagrangian method
      combined with a preconditioned iterative solver for a cardiac mechanics benchmark
      suite are presented to show its improved performance.

PMID- 29181890
TI  - Pediatric acute kidney injury induced by concomitant vancomycin and piperacillin
      tazobactam.
AB  - BACKGROUND: Vancomycin is very commonly used in combination with piperacillin
      tazobactam (PTZ) as the initial empiric treatment for moderate-severe infection,
      whenever coverage for both methicillin-resistant Staphylococcus aureus and
      Pseudomonas aeruginosa is required. The combination of vancomycin and PTZ in
      adults has recently been reported to significantly increase the risk of acute
      kidney injury (AKI) relative to vancomycin monotherapy; such reports in
      pediatrics, however, are sparse. METHODS: A retrospective chart review was
      conducted of pediatric patients, aged 0-14 years, who were admitted to the
      general wards or intensive care unit and developed AKI after receiving vancomycin
      and PTZ concomitantly for >48 h. AKI is defined as a decrease in estimated
      glomerular filtration rate >=50% from baseline. Cases were identified by
      reviewing the Adverse Drug Reaction program database at King Saud University
      Medical City in Saudi Arabia from January 2015 to June 2016. RESULTS: Eight
      children admitted to the present hospital and who received concomitant vancomycin
      and PTZ treatment for pneumonia (n = 7) or febrile neutropenia (n = 1) developed
      drug-induced nephrotoxicity. Drug Interaction Probability Scale (DIPS) score for
      causation assessment was 9 in all cases (highly probable). CONCLUSION: Caution in
      utilizing the combination of vancomycin and PTZ is warranted in pediatric
      patients. Health-care professionals should be vigilant if this combination is to
      be initiated, and ensure close monitoring of renal function. Antibiotic therapy
      de-escalation should be considered as soon as culture results are available.

PMID- 29181891
TI  - Fluid-structure interaction of a pulsatile flow with an aortic valve model: A
      combined experimental and numerical study.
AB  - The complex fluid-structure interaction problem associated with the flow of blood
      through a heart valve with flexible leaflets is investigated both experimentally
      and numerically. In the experimental test rig, a pulse duplicator generates a
      pulsatile flow through a biomimetic rigid aortic root where a model of aortic
      valve with polymer flexible leaflets is implanted. High-speed recordings of the
      leaflets motion and particle image velocimetry measurements were performed
      together to investigate the valve kinematics and the dynamics of the flow. Large
      eddy simulations of the same configuration, based on a variant of the immersed
      boundary method, are also presented. A massively parallel unstructured finite
      volume flow solver is coupled with a finite-element solid mechanics solver to
      predict the fluid-structure interaction between the unsteady flow and the valve.
      Detailed analysis of the dynamics of opening and closure of the valve are
      conducted, showing a good quantitative agreement between the experiment and the
      simulation regarding the global behavior, in spite of some differences regarding
      the individual dynamics of the valve leaflets. A multicycle analysis (over more
      than 20 cycles) enables to characterize the generation of turbulence downstream
      of the valve, showing similar flow features between the experiment and the
      simulation. The flow transitions to turbulence after peak systole, when the flow
      starts to decelerate. Fluctuations are observed in the wake of the valve, with
      maximum amplitude observed at the commissure side of the aorta. Overall, a very
      promising experiment-vs-simulation comparison is shown, demonstrating the
      potential of the numerical method.

PMID- 29181892
TI  - Comparison of peri-implant clinical and radiographic status around short (6 mm in
      length) dental implants placed in cigarette-smokers and never-smokers: Six-year
      follow-up results.
AB  - BACKGROUND: It is hypothesized that peri-implant clinical and radiographic
      inflammatory parameters (probing depth [PD], bleeding on probing [BOP] and plaque
      index [PI]; and radiographic (crestal bone loss [CBL]) are worse among cigarette
      smokers (CS) compared with never-smokers (NS) with short implants. PURPOSE: The
      present 6-year follow-up retrospective study compared the peri-implant clinical
      and radiographic parameters in CS and NS with short dental implants (6 mm in
      length). MATERIALS AND METHODS: Fifty-six male individuals were included. These
      individuals divided into 2 groups as follows: (a) Group-1: 29 self-reported
      systemically healthy CS with 48 short-implants; and (b) Group-2: 27 self-reported
      systemically healthy NS with 43 short implants. Peri-implant PD, PI, BOP, and CBL
      were measured. Group comparisons were done using the Kruskal-Wallis test and
      sample size was estimated. Level of significance was set at P values < .05.
      RESULTS: In groups 1 and 2, the follow-up durations were 6.2 +/- 0.1 years and
      6.1 +/- 0.3 years, respectively. A cigarette smoking history of 8.9 +/- 3.6 pack
      years was reported by individuals in Group-1. At follow-up, scores of peri
      implant PD, BOP, PI, and mesial and distal CBL were comparable around short
      implants in both groups. CONCLUSION: Under strict oral hygiene maintenance
      protocols, short dental implants can remain functionally stable in CS in a manner
      similar to NS.

PMID- 29181893
TI  - Developing inclusive residential care for older lesbian, gay, bisexual and trans
      (LGBT) people: An evaluation of the Care Home Challenge action research project.
AB  - There have been substantial achievements in legislative and human rights for
      lesbian, gay, bisexual and transgender (LGBT) older people and their visibility
      in health and social care has equally increased. These appear to have surpassed
      the ability of care services to meet their needs given documented concerns about
      the accessibility, inclusiveness and safety of care services particularly
      institutionalised care. This requires systemic change not easy to operationalise.
      This paper describes an action research initiative where six care homes belonging
      to a national care provider, collaborated to assess and develop their services
      with the support of local LGBT "Community Advisors" and academic partners. Framed
      within Rogers' (2003) change management framework and combined with a
      participatory leadership approach, a programme of intervention was implemented
      comprising structured activities around seven key areas thought to promote LGBT
      inclusion. A formal evaluation was conducted involving 35 pre- and post
      intervention qualitative interviews with 18 people (community advisors; care home
      managers and senior managers). The findings are presented across three key themes
      (1) starting points on the journey; (2) challenges encountered along the journey
      (organisational and interpersonal); and (3) making change happen; opportunities,
      initiatives and gains. We make recommendations on the value of a programme
      approach for achieving tangible outcomes that demonstrate increased inclusion for
      older LGBT people living in long-term care settings.

PMID- 29181894
TI  - Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so
      far?
AB  - BACKGROUND: Helicobacter pylori has changed radically gastroenterologic world,
      offering a new concept in patients' management. Over time, more medical data gave
      rise to diverse distant, extragastric manifestations and interactions of the
      "new" discovered bacterium. Special interest appeared within the field of
      neurodegenerative diseases and particularly Alzheimer's disease, as the latter
      and Helicobacter pylori infection are associated with a large public health
      burden and Alzheimer's disease ranks as the leading cause of disability. However,
      the relationship between Helicobacter pylori infection and Alzheimer's disease
      remains uncertain. METHODS: We performed a narrative review regarding a possible
      connection between Helicobacter pylori and Alzheimer's disease. All accessible
      relevant (pre)clinical studies written in English were included. Both affected
      pathologies were briefly analyzed, and relevant studies are discussed, trying to
      focus on the possible pathogenetic role of this bacterium in Alzheimer's disease.
      RESULTS: Data stemming from both epidemiologic studies and animal experiments
      seem to be rather encouraging, tending to confirm the hypothesis that
      Helicobacter pylori infection might influence the course of Alzheimer's disease
      pleiotropically. Possible main mechanisms may include the bacterium's access to
      the brain via the oral-nasal-olfactory pathway or by circulating monocytes
      (infected with Helicobacter pylori due to defective autophagy) through disrupted
      blood-brain barrier, thereby possibly triggering neurodegeneration. CONCLUSIONS:
      Current data suggest that Helicobacter pylori infection might influence the
      pathophysiology of Alzheimer's disease. However, further large-scale randomized
      controlled trials are mandatory to clarify a possible favorable effect of
      Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before
      the recommendation of short-term and cost-effective therapeutic regimens against
      Helicobacter pylori-related Alzheimer's disease.

PMID- 29181895
TI  - Body composition, appetite-related hormones, adipocytokines, and heart failure in
      adult patients with congenital heart disease: A preliminary study.
AB  - OBJECTIVES: To assess body composition and relationships among body composition,
      appetite-related hormones, adipocytokines, and heart failure (HF) in adult
      patients with congenital heart disease (CHD). PATIENTS: This prospective study
      enrolled 46 consecutive adult patients with CHD and 12 age-matched healthy
      controls. The patients and control subjects were divided into four groups: 13
      patients with Fontan circulation (group A), 16 patients with cyanosis (group B),
      17 patients who previously underwent biventricular repair (group C), and 12 age
      matched healthy controls. DESIGN: Body composition was measured using InBody730,
      and levels of appetite-related hormones (ghrelin and leptin) and adipocytokines
      (leptin, interleukin-6, and tumor necrosis factor-alpha) were determined.
      Relationships of these measurements between severe HF, defined as New York Heart
      Association functional class III-IV and/or recent repeated unscheduled
      hospitalizations due to HF, were examined using univariate logistic analysis.
      RESULTS: Mean patient age was 32.1 +/- 7.4 years. The skeletal muscle mass was
      significantly decreased in groups A and B compared with that in controls.
      Interestingly, ghrelin levels in groups A and B were also significantly lower
      than those in controls. Univariate logistic analysis revealed that ghrelin level,
      percent body fat, and pulse oximetric oxygen saturation were significantly
      associated with severe HF. CONCLUSIONS: Patients with Fontan circulation and
      those with cyanosis might be at a risk of sarcopenia. Despite the decreased
      skeletal muscle mass and increased body fat, ghrelin levels in these patients
      were decreased. These changes might have a negative impact on HF in these
      patients.

PMID- 29181896
TI  - Constraining the Teratogenicity of Pesticide Pollution by a Synthetic
      Nanoreceptor.
AB  - The teratogenicity of the pesticide nereistoxin (NTX) and its derivative
      thiocyclam (THI) towards aquatic life was dramatically constrained by a synthetic
      nanoreceptor, cucurbit[7]uril, through selective encapsulation of the pesticides
      (KCB[7]-NTX of 3.24(+/-0.31)*106  m-1 and KCB[7]-THI of 7.46(+/-0.10)*105  m-1 ),
      as evidenced by the rate of hatchability, morphology development, and tyrosinase
      activity of zebrafish larvae incubated with the pesticides (3-300 MUm) in the
      absence and in the presence of 300 MUm cucurbit[7]uril, demonstrating the
      significant potential of the nanoreceptor in managing ecological pollution of
      these pesticides.

PMID- 29181898
TI  - Nine new species of the spider genus Stedocys (Araneae, Scytodidae) from China
      and Thailand.
AB  - Nine new species of the genus Stedocys Ono, 1995 are described: Stedocys
      gaolingensis Wu & Li sp. n. (??, Guangxi), S. huangniuensis Wu & Li sp. n. (?,
      Guangxi), S. ludiyanensis Wu & Li sp. n. (??, Guangxi), S. matuoensis Wu & Li sp.
      n. (?, Guangxi), S. pulianensis Wu & Li sp. n. (?, Guangxi), S. shilinensis Wu &
      Li sp. n. (??, Hainan), S. xianrenensis Wu & Li sp. n. (??, Guangxi), S.
      xiangzhouensis Wu & Li sp. n. (??, Guangxi) from China, and S. zhaoi Wu & Li sp.
      nov. (??, Kanchanaburi) from Thailand. Diagnoses of nine new species are
      provided. DNA barcodes for six new species are documented for future use and as
      proof of molecular differences between these species.

PMID- 29181899
TI  - A new species of rain-pool frog (Dicroglossidae: Fejervarya) from western
      Thailand.
AB  - We describe a new species, Fejervarya muangkanensissp. nov., based on a series of
      specimens collected from Ban Tha Khanun, Thong Pha Phum District, Kanchanaburi
      Province, Thailand. The new species is easily distinguished from its congeners by
      morphological and molecular data, and can be diagnosed by the following
      characters: (1) small size (adult male snout-vent length (SVL) 33.5 mm; female
      SVL 40.0-40.9 mm); (2) tympanum small, discernible but unclear; (3) poorly
      developed toe webbing; (4) no lateral line system in adults; (5) characteristic
      "Fejervaryan" lines present in females; and (6) femoral glands absent. Molecular
      phylogenetic analysis of mitochondrial 16S rRNA further supports it as a distinct
      lineage and distinguishes it from its congeners for which sequences are
      available.

PMID- 29181900
TI  - A new species of the Southeast Asian genus Opisthotropis (Serpentes: Colubridae:
      Natricinae) from western Hunan, China.
AB  - A new species of natricine snake of the Southeast Asian genus Opisthotropis Gu
      nther, 1872 is described from western Hunan Province of China based on both
      mitochondrial DNA and morphological data. The new species is morphologically most
      similar and genetically most closely related to O. cheni Zhao, 1999 and O.
      latouchii (Boulenger, 1899), but possesses considerable genetic divergence (p
      distance 5.1%-16.7%) and can be differentiated from all other congeners by a
      combination of the following morphological characters: (1) body size large (total
      length 514-586 mm) and strongly built; (2) dorsal scale rows 17 throughout,
      feebly keeled anteriorly and moderately keeled posteriorly; (3) ventral scales
      147-152, subcaudal scales 54-62; (4) preocular absent, loreal elongated and
      touching orbit; (5) supralabials 8-9, fifth and sixth entering obit; (6) anterior
      temporals short, length 1.74-2.04 times longer than width; (7) maxillary teeth
      subequal, 28-30; (8) dorsal surface of head with distinct irregular yellow
      stripes and markings edged with ochre; (9) body with clear black and yellow
      longitudinal streaks, partly fused to several lighter patches or thicker stripes
      anteriorly; and (10) venter pale yellow, with asymmetric blackish speckles along
      outer margin. We present an updated diagnostic key to all members of the genus
      Opisthotropis, and recommendations on the ecological study for the group are
      provided.

PMID- 29181902
TI  - Myanmarorchestia victoria sp. nov. (Crustacea, Amphipoda, Talitridae), a new
      species of landhopper from the high altitude forests in Myanmar.
AB  - Myanmarorchestia victoriasp. nov. is described from high altitude habitats in
      Myanmar. The new species differs morphologically from its congeners by palp of
      maxilliped narrow; sexually dimorphic gnathopod II, propodus of male chelate and
      propodus of female mitten-shaped; and dimorphic uropod II, outer ramus of male
      with small teeth distally, outer ramus of female with three distal spines.
      Analysis of DNA barcode sequences and niche distinctiveness support recognition
      of the new species.

PMID- 29181901
TI  - Bird diversity in northern Myanmar and conservation implications.
AB  - We conducted four bird biodiversity surveys in the Putao area of northern Myanmar
      from 2015 to 2017. Combined with anecdotal information collected between 2012 and
      2015, we recorded 319 bird species, including two species (Arborophila mandellii
      and Lanius sphenocercus) previously unrecorded in Myanmar. Bulbuls
      (Pycnonotidae), babblers (Timaliidae), pigeons and doves (Columbidae), and
      pheasants and partridges (Phasianidae) were the most abundant groups of birds
      recorded. Species richness below 1 500 m a. s. l. was higher than species
      richness at higher elevations. Our results suggest that the current protected
      areas in this region should be expanded to lower elevations to cover critical
      conservation gaps.

PMID- 29181903
TI  - A new species of sisorid catfish of the genus Exostoma from the Salween drainage,
      Yunnan, China.
AB  - A new species of the sisorid catfish genus Exostoma Blyth, 1860 was collected
      from two hill-stream tributaries of the Nujiang (Salween River) drainage in
      Gaoligong Mountain, south-western Yunnan Province, China from 2003 to 2006 and
      from two tributaries of the Salween River in Cangyuan County, Lingcang
      Prefecture, Yunnan Province, China (in 2007) and in Yongde County, Lingcang
      Prefecture, Yunnan Province, China (in 2015). Exostoma gaoligongensesp. nov. is
      the 10th species of the genus and is most similar to E. vinciguerrae in
      morphology but can be distinguished by pelvic fin reaching anus vs. not reaching;
      maxillary barbels just reaching or slightly surpassing pectoral-fin origin vs.
      surpassing pectoral-fin origin or even reaching posterior end of gill membrane;
      abdominal vertebrae 23-25 vs. 25-27; length of dorsal fin/dorsal to adipose
      distance 90.3%-287.0% vs. 59.2-85.7. A key to Exostoma spp. is provided.

PMID- 29181904
TI  - Five newly recorded Cyprinid fish (Teleostei: Cypriniformes) in Myanmar.
AB  - Freshwater fish from the Putao and Myitkyina areas were collected in three
      ichthyofaunal surveys of the Mali Hka River and tributaries in and around
      Khakaborazi National Park and Hponkanrazi Wildlife Sanctuary, Kachin State, from
      2014-2016. Tor yingjiangensis Chen et Yang 2004, Tor qiaojiensis Wu et al. 1977,
      Garra qiaojiensis Wu et al. 1977, Garra bispinosa Zhang 2005, and Schizothorax
      oligolepis Huang 1985, originally described from the upper Irrawaddy
      (Ayeyarwaddy) River in China, are first reported herein as new records to
      Myanmar. Counts, measurements, descriptions, photographs, and distributions of
      the specimens of the five newly recorded species are provided.

PMID- 29181905
TI  - Complete mitochondrial genome of the leaf muntjac (Muntiacus putaoensis) and
      phylogenetics of the genus Muntiacus.
AB  - The leaf muntjac (Muntiacus putaoensis) is an endemic deer species found in the
      east trans-Himalayan region. In recent years, population numbers have decreased
      due to heavy hunting and habitat loss, and little genetic data exists for this
      species, thus our knowledge of distribution rangs and population sizes likewise
      remain limited. We obtained mtDNA genes and the complete mitochondrial genome
      sequence of M. putaoensis using PCR, followed by direct sequencing. The complete
      mitogenome sequence was determined as a circular 16 349 bp mitochondrial genome,
      containing 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and one
      control region, the gene composition and order of which were similar to most
      other vertebrates so far reported. Most mitochondrial genes, except for ND6 and
      eight tRNAs, were encoded on the heavy strand. The overall base composition of
      the heavy strand was 33.1% A, 29.3% T, 24.2% C, and 13.4% G, with a strong AT
      bias of 62.4%. There were seven regions of gene overlap totaling 95 bp and 11
      intergenic spacer regions totaling 74 bp. Phylogenetic analyses (ML and BI) among
      the Muntiacus genus based on the sequenced of mitogenome and ND4L-ND4 supported
      M. putaoensis as a member of Muntiacus, most closely related to M. vuquangensis.
      However, when analyses based on cyt b included two more muntjacs, M.
      truongsonensis was most closely related to M. putaoensis rather than M.
      vuquangensis, and together with M. rooseveltorum, likely forming a M.
      rooseveltorum complex of the species. This study will help in the exploration of
      the evolutionary history and taxonomic status of the leaf muntjac, as well as its
      protection as a genetic resource.

PMID- 29181907
TI  - ?

PMID- 29181906
TI  - The problem of coercion.

PMID- 29181909
TI  - ?

PMID- 29181908
TI  - The eating disorder that paved the way for anabolic steroid use.

PMID- 29181910
TI  - ?

PMID- 29181911
TI  - ?

PMID- 29181912
TI  - [Does acupuncture work?].

PMID- 29181913
TI  - ?

PMID- 29181914
TI  - ?

PMID- 29181915
TI  - ?

PMID- 29181916
TI  - ?

PMID- 29181917
TI  - ?

PMID- 29181919
TI  - ?

PMID- 29181918
TI  - ?

PMID- 29181920
TI  - ?

PMID- 29181921
TI  - ?

PMID- 29181922
TI  - ?

PMID- 29181923
TI  - ?

PMID- 29181924
TI  - [Intravenous lipoma].

PMID- 29181925
TI  - ?

PMID- 29181926
TI  - [Do you know the secret services?].

PMID- 29181927
TI  - [What makes your inner clock tick?].

PMID- 29181928
TI  - ?

PMID- 29181929
TI  - ?

PMID- 29181930
TI  - ?

PMID- 29181931
TI  - Local emergency medical communication centres - staffing and populations.
AB  - BACKGROUND: There are several examples of inadequate staffing at local emergency
      medical communication centres (LEMCs) resulting in limited availability and long
      waits on the telephone. There are no guidelines for population size or the
      staffing of a LEMC. In the following, we present models of catchment areas and
      staffing. MATERIAL AND METHOD: Traffic intensity on Saturdays and Sundays was
      based on data on figures for patient contacts at seven LEMCs in 2014 and 2015. We
      defined the minimum optimal population base as at least 50 % probability of >= 10
      contacts in the course of a night duty. The Erlang-C formula was used to estimate
      service level and hence staffing requirements on the basis of population and
      response-time requirements. We have surveyed the combined staffing requirements
      of all the LEMCs in Norway. RESULT: The minimum optimal population base was 29
      134. In 2016, 48 of 103 LEMCs were smaller than this. In order to be able to
      satisfy the response-time requirements in the Norwegian Emergency Medicine
      Regulations, 112 LEMC night operators and 158 day operators would be necessary
      for the whole of Norway. A reduction of the response-time requirement from 120 to
      ten seconds would require 9.8 % more operators at night and 17 % more operators
      during the day. INTERPRETATION: The models we have presented provide a basis for
      planning the population base and staffing of LEMCs. Significantly stricter
      response-time requirements will result in limited need for more personnel.

PMID- 29181932
TI  - Cardiovascular disease and diabetes in patients with African or Asian background.
AB  - BACKGROUND: Population groups of different ancestry appear to have varying
      prevalence of diabetes, different risks of developing cardiovascular disease and
      different responses to certain drugs that are used for these conditions. We
      wished to review the literature in this field. MATERIAL AND METHOD: We have
      performed searches in several databases for systematic review articles published
      from the year 2000 onwards, and supplemented these with articles from reference
      lists, our own literature archives and a pyramid search in the Norwegian
      Electronic Health Library database. Altogether 37 articles were included.
      RESULTS: With regard to diagnosed diabetes, the prevalence of coronary heart
      disease and stroke varies among groups of South Asian, East Asian, African and
      European ancestry. In patients of South Asian ancestry, the risk of coronary
      heart disease appears to be twice that of Europeans, and the disease occurs 5-10
      years earlier. The prevalence of stroke is especially high in persons of African
      ancestry. Risk factors such as dyslipidemia and hypertension are distributed
      differently among these groups. The therapeutic response to drugs such as beta
      blockers, ACE inhibitors and various statins differs; for example, statin doses
      in Asians may often be halved in relation to those used for Caucasians, and ACE
      inhibitors are not recommended as monotherapy for hypertension in persons of
      African ancestry. These differences are partly attributable to variations in
      genetic disposition. INTERPRETATION: The findings are clinically significant -
      better insight in this field enables optimal tailoring of treatment for each
      patient, with more rapid achievement of goals and reduced risk of adverse
      effects. The recommendations given in this article are consistent with and
      complement the Directorate of Health's revised guidelines for the treatment of
      diabetes.

PMID- 29181934
TI  - ?

PMID- 29181933
TI  - [How to show equality?].

PMID- 29181935
TI  - ?

PMID- 29181936
TI  - ?

PMID- 29181937
TI  - ?

PMID- 29181938
TI  - ?

PMID- 29181939
TI  - ?

PMID- 29181941
TI  - ?

PMID- 29181940
TI  - ?

PMID- 29181942
TI  - [Emergency medical communication center and RAS syndrome].

PMID- 29181943
TI  - ?

PMID- 29181944
TI  - [The family physician system is crumbling - what now?].

PMID- 29181945
TI  - ?

PMID- 29181946
TI  - ?

PMID- 29181947
TI  - ?

PMID- 29181948
TI  - ?

PMID- 29181949
TI  - ?

PMID- 29181950
TI  - ?

PMID- 29181951
TI  - ?

PMID- 29181952
TI  - Coronary angiography in non-ST-elevation acute myocardial infarction - whom and
      when?

PMID- 29181953
TI  - Irisin levels correlate with bone mineral density in soccer players.
AB  - Irisin, a novel myokine produced in response to physical exercise by skeletal
      muscle, displays anabolic effect on bone and can improve the bone-loss-induced
      osteoporosis in hind limb suspended mice. It is well known that muscles
      positively impact the skeleton and in different sports, including soccer, total
      body bone mineral density (TB-BMD) is elevated. Therefore, we have investigated
      the correlation between irisin serum levels and total and bone sub-regional BMD
      in soccer players never studied before. In this study, Caucasian football players
      of Bari team have been enrolled. Their sera were collected to measure by ELISA
      kit irisin levels and by dual-energy X-ray absorptiometry (DEXA) analysis
      measurements of BMD (g * cm-2) in the whole body and different bone sub-regions
      (head, arms, legs, ribs, dorsal vertebrae, lumbar vertebrae, pelvis) were
      performed. The BMC (g) was measured in the whole body. By means of Pearson's (R)
      and Cohen's (d) coefficient we investigated the linear association between the
      irisin serum levels and BMD. In soccer players, we have found a positive
      correlation between irisin and TB-BMD as demonstrated by the values of Pearson
      and Cohen's (d) coefficient. Furthermore, linear association was detected between
      irisin and BMD of different bone-site such as right arm, lumbar vertebrae and
      head. A positive trend was also observed analyzing circulating levels of irisin
      and bone mineral content as well as total Z-score. In conclusion, we have
      demonstrated the correlation between irisin and total or bone sub-regional BMD in
      soccer players for the first time, an additional systemic effect of the "sport
      hormone" defined myokine.

PMID- 29181954
TI  - C3f is a potential tool for the staging of osteoarthritis.
AB  - An attractive method for osteoarthritis (OA) staging is the measurement of
      biochemical markers in biological fluids, which could reflect dynamic and
      quantitative changes in joint remodeling and therefore disease progression.
      Proteome analysis has been recognized as one of the most effective tools to
      explore biomarkers as it can furnish a wealth of information in both diagnosis
      and prognosis of diseases. We have recently described an innovative tool for
      peptidome and lipidome profiling of fluids based on mesoporous aluminosilicate
      (MPAS) and Matrix-Assisted Laser Desorption/Ionization time-of-flight Mass
      Spectrometry (MALDI-TOF MS). The aim of this study was to analyze peptide
      profiles of human synovial fluid in patients with different grade of OA using
      MALDI-TOF-MS technique in order to identify potential markers of disease
      progression. Twenty-five patients older than 50 years and affected by primary
      knee OA diagnosed according to clinical and radiological criteria were enrolled.
      For each patient a synovial fluid sample was aspirated from the affected knee and
      analyzed using MALDI-TOF-MS technique. A statistically significant difference in
      the normalized area of two peaks (m/z=1865 and m/z=2021) was detected among
      different stages of OA. The 2 peaks were identified as Complement C3 peptide
      fragments: C3f and C3f Des-Arg. The expression levels of these two peptides
      (m/z=1865 and 2021) decreased with the progression of OA degrees severity (rhos=
      0.434, p=0.03, and rhos=-0.532, p=0.006, respectively). This marker may be a
      useful tool for assessing the severity of knee OA and it may be a novel target
      for drug discovery, specifically for the development of disease modifying OA
      drugs. However further studies are required to clarify the role of C3f in OA
      pathogenesis.

PMID- 29181955
TI  - Soft tissue adhesion patterns over Trevira tube on modular endoprosthesis for
      malignant bone tumours: an in vitro study.
AB  - A reliable and effective technique in case of limb salvage surgery after
      resection of extensive bone tumors is represented by the implant of modular or
      custom-made megaprosthesis. Fixation of the residual surrounding soft tissue on
      the implant represent a challenge for the surgeon and the use of a polyethylene
      terephthalate (PET) tube over it, also known as Trevira, is currently a common
      choice for reattachment with good clinical outcomes. We compared fibroblastic
      cell culture potential over simple titanium coating vs titanium surrounded by
      Trevira and evaluated cell viability and replication at 24, 48 and 72 h using MTT
      cell growth assay and scanning electron microscopy to determine if there was any
      difference in the potential of cell growth associated to the material used. No
      significant difference was found at different timings in terms of total cell
      count for cultures over the two materials, but the absolute cell count was
      slightly higher in the Trevira group in the early time points, reversing the
      trend at 72 h of incubation. Ninety-four % of the cells analyzed were vital,
      regardless of the materials involved in the experiment, confirming the
      biocompatibility of titanium and PET. According to the results shown, we are able
      to confirm the in vitro safety and efficacy, in terms of newly formed cells
      extension and adhesion pattern, of using an attachment tube made from Trevira
      fibers surrounding an oncological megaprosthesis in order to achieve the most
      anatomical reinsertion of remaining soft tissue following resection.

PMID- 29181956
TI  - Infectious diseases in Poland in 2015
AB  - PURPOSE OF THE STUDY: This is the next annual analysis of the situation of
      infectious and parasitic diseasesin Poland in 2015 within the framework of the
      Epidemiological Chronicle of Przeglad Epidemiologiczny- Epidemiological Review.
      Its purpose is to identify potential threats to the health of populations from
      infectiousdiseases occurring in Poland with reference to other parts of the
      globe. MATERIAL AND METHODS: This paper is an introduction to more detailed
      studies of the epidemiologicalsituation of selected infectious diseases and
      summarizes the results of the surveillance of infectious diseasesin Poland in
      2015. References to epidemiological situation in other countries are limited to
      situations that mayaffect current or potential occurrence of the disease in
      Poland.The main source of epidemiological information for this summary is the
      data from the reports of the State SanitaryInspection included in the annual
      bulletins "Infectious Diseases and Poisonings in Poland in 2015" and"Vaccination
      in Poland in 2015" (1, 2). The epidemiological situation of particular diseases
      is further elaboratedin the Epidemiological Chronicle of the same issue of the
      Epidemiological Review.Data on deaths are based on the presentation of the
      Demographic and Labor Market Department of the CentralStatistical Office on
      deaths from infectious and parasitic diseases registered in Poland in 2015 and
      earlier. RESULTS: For a long time, the most common diseases among epidemiological
      surveillance it is upper respiratorytract infections classified as "influenza and
      suspected influenza". In 2015, the number of cases was3,843,438 (9 994,7 /
      100,000). As to compare with the 2014's incidence, this was an increase of
      22.6%.In 2015, incidence of intestinal infections with etiology of salmonella
      increased by 2.8% compared to the previousyear, but compared to the median of
      2009-2013 was 2.5% lower.A serious epidemiological problem is a strong upward
      trend in nosocomial infections including infections causedby Clostridium
      difficile. In 2015, 8.976 (23.3 / 100,000) of these cases were reported. They
      caused 491 deaths.Compared to the previous year, the increase in incidence was
      39.8%. Compared with the median of 2009-2013it was an increase of 89.7%.In 2015,
      there was a continuation of observed for more than a dozen years the unfavorable
      trend of intestinalinfections caused by noroviruses. There were recorded at 3,637
      (9.5 / 100,000) of those infections.Among viral intestinal infections, rotavirus
      infections in children are a particularly important problem. In 2015,as compared
      with 2014, the increase of incidence in the general population was not high, only
      0.5%, but to themedian of 2009-2013 it was 44.4%.An important group of intestinal
      infections, diarrhea in children under 2 years of age, had a slight decrease
      (by0.3%) in the category of bacterial infections in 2015, but increased by 26.7%
      in the category of bacterial poisoningsand 5.9% in the category of viral
      infections.In 2015, there were 4956 cases of pertussis (512.9 / 100,000), which
      was an increase in the incidence comparedwith the previous year by 136.2%, and
      compared with the 2009-2013 median by 127.4%.After the epidemic of rubella
      outbreaks in 2013, in the year 2014, the incidence dropped by 84.7% and in
      2015,the decrease was 65.9%. One case of congenital rubella has been
      reported.Most measles infections are imported infections or in contact with them
      in the country. In 2015 the number ofcases was 48 (0.12 / 100,000). In 2015, the
      number of invasive diseases caused by H. influenzae was 62 (0.16 /100,000).
      Compared to the previous year, this was an increase of 51.3%.The number of
      invasive diseases caused by Streptococcus pneumoniae in 2015 was 979 cases.
      Compared to2014, this was an increase of 39.0%. When compared with the median of
      2009-2013, increase was 128.1%.In 2015, number of reported cases of hepatitis B
      was 3,518 (9.1 / 100,000), which was 122.7% higher than themedian of 2009-2013.
      Newly diagnosed C-type infections were reported to be 4,285 (11.1 / 100,000), an
      increaseof 91.6% over the median of 2009-2013. Such a large increase in reported
      cases is related, inter alia to the introductiona new, more sensitive case
      definition in 2014.The incidence of Lyme disease has been on the rise in the last
      fifteen years. In 2015, 13,625 cases (35.4 /100,000) were reported, which, with
      an insignificant decrease compared to 2014, gives rise to 49.1% over themedian of
      2009-2013.The downward trend in the incidence of tuberculosis (all forms of
      tuberculosis) is clearly persistent. In 2015, theincidence of this disease
      decreased compared to the previous year from 17.4 to 16.7 / 100,000.In 2015 were
      reported 1,281 cases of newly diagnosed HIV (3,33 / 100,000). It was an increase
      of 13.0%. Thenumber of AIDS cases decreased by 13.5% compared to the previous
      year.Reported cases of malaria involve people who have been infected abroad in
      endemic malaria areas. In 2015 therewere reported 29 such cases.None of the cases
      of diphtheria, chronic childhood paralysis, rabies and viral hemorrhagic fever
      except for denguehave been reported in 2015. There were reported 12 cases of
      dengue imported from endemic regions.In Poland in 2015 number of deaths from all
      infectious and parasitic diseases was 2,199. The share of deaths dueto infectious
      diseases in the total number of deaths was 0.54% and mortality was 5.5 per
      100,000 population. Themajority of deaths were caused by tuberculosis and its
      consequences (25.7%) and intestinal infections caused byClostridium difficile
      (23.2%).

PMID- 29181957
TI  - Measles in Poland in 2015
AB  - BACKGROUND: In 1998 Poland, along with all other Member States in the WHO
      European Region, implementedMeasles Elimination Programme coordinated by WHO. It
      requires achieving and maintaining veryhigh vaccine coverage (>95%), recording
      all cases and suspected cases of measles, and laboratory testing ofall suspected
      measles cases in the WHO Reference Laboratory. In Poland it is a Laboratory of
      Department ofVirology, NIPH-NIH. In order to confirm or exclude the case of
      measles specific measles IgM antibodies shouldbe measured using Elisa test, or
      molecular testing (PCR) should be performed to detect the presence measlesvirus
      RNA in biological material. AIM: To assess epidemiological situation of measles
      in Poland in 2015, including vaccination coverage in Polishpopulation, and
      Measles Elimination Program implementation status. METHODS: The descriptive
      analysis was based on data retrieved from routine mandatory surveillance
      systemand published in the annual bulletins "Infectious diseases and poisonings
      in Poland in 2015" and "Vaccinationsin Poland in 2015", and measles case-based
      reports from 2015 sent to the Department of Epidemiology NIPHNIHby Sanitary
      Epidemiological Stations. RESULTS: In total, there were 48 measles cases
      registered in Poland in 2015 (incidence 0.12 per 100,000), fromwhich 30 cases
      (62.5%) were confirmed with laboratory test. That was less than in 2014 - when
      110 cases werereported and incidence was 0,29.In 2015, a total number of reported
      cases and suspected cases of measles was133, among them 48 cases (incidence 0.12
      per 100,000) meet the criteria and were registered in Poland. In comparisonto the
      previous year (110 cases; 0.29) there was registered dicrease in the number of
      cases. Thirty cases(36.1%) were confirmed with laboratory tests. The highest
      incidence rate was observed among children in agegroup 0-4 (0.59). In 2015, 26
      cases (54.2%) were hospitalized due to measles. No deaths from measles were
      reported.Vaccination coverage of children and youth aged 2-11 years ranged from
      77.9% do 99.5% (primary vaccinationin children born in 2009-2013) and from 71.5%
      do 88.9% (booster dose in children born in 2005-2008). SUMMARY AND CONCLUSIONS:
      The epidemiological situation of measles deteriorated in 2015 in comparisonto
      proceding year. The sensitivity of measles surveillance improved but is still
      insufficient. It is necessaryto further promote Measles Elimination Program in
      Poland, to improve measles surveillance system and tomaintain the high
      immunization coverage.

PMID- 29181958
TI  - Rubella in Poland in 2015
AB  - BACKGROUND: In 2004, Poland has adopted the WHO goal of rubella elimination and
      congenital rubellasyndrome prevention. The main target of the Programme is to
      stop transmission of the virus in the environmentand prevention of congenital
      rubella cases between children. This can be achieved by carrying out the
      vaccination.Participation in the rubella elimination program requires clinical
      diagnosis of rubella to be confirmed withlaboratory test. A laboratory-confirmed
      case is a suspected case with a positive blood test for rubella-specificIgM or/
      and isolation of rubella virus. Isolation of rubella viruses and genotyping is an
      important components forconfirming connections between cases or excluding cases
      during investigations.Vaccination against rubella was introduced in 1987,
      initially only in 13 year-old girls. Among men, the incidenceof measles remained
      high creating a risk of infection of non-immune pregnant women which may lead to
      thedevelopment of congenital rubella syndrome in the child. Since 2003, single
      jab vaccination against rubella,measles and mumps is used- MMR vaccine for all
      children: primary vaccination at the age 13-15 months. AIM: To assess
      epidemiological situation of rubella in Poland in 2015, including vaccination
      coverage in polishpopulation. METHODS: The descriptive analysis was based on data
      retrieved from routine mandatory surveillance systemand published in the annual
      bulletins "Infectious diseases and poisonings in Poland in 2015" and
      "Vaccinationsin Poland in 2015". RESULTS: In 2015, there was a decrease in the
      number of rubella cases - with registered 2 027 cases (in 2014- 5 891 cases) -
      and a decline in incidence (from 15.3 per 100 000 to 5.3). The highest incidence
      rate, regardlessof gender and the environment, was observed among children aged 0
      4 years (46.7 per 100,000). The incidenceof rubella in boys and men was similar
      to the incidence in girls and women (5.5 versus 5.0). In 2015, no cases
      ofcongenital rubella syndrome were registered. SUMMARY AND CONCLUSIONS: In 2015,
      there was a decrease in the number of rubella cases. In PolandRubella is reported
      exclusively on the basis of the clinical picture. The proportion of laboratory
      tests confirming/excluding rubella infection is still very low in Poland. In
      2015, only 1.1% of rubella cases were laboratoryconfirmed.

PMID- 29181959
TI  - Mumps in Poland in 2015
AB  - BACKGROUND: Vaccination against mumps from 2003 is mandatory in Poland and given
      as two dose schemewith MMR vaccine (mumps, measles, and rubella). Earlier this
      vaccination was only recommended. Despiteobserved decline in mumps incidence for
      over a decade which is a result of conducted vaccinations, mumps isstill a common
      disease among the children (1-3). AIM: To assess epidemiological situation of
      mumps in Poland in 2015, including vaccination coverage in Polishpopulation, in
      comparison to previous years. METHODS: The descriptive analysis was based on data
      retrieved from routine mandatory surveillance systemand published in the annual
      bulletins "Infectious diseases and poisonings in Poland in 2015" and
      "Vaccinationsin Poland in 2015" (4;5). Mumps cases were classified according to
      the criteria of surveillance case definitionimplemented in the European Union
      (Commission Decision of 28 April 2008 amending Decision 2002/253/EC).National
      Immunisation Programme for year 2015 was also used (6). RESULTS: In total, there
      were 2 208 mumps cases registered in Poland in 2015. Incidence of mumps was
      5.7per 100,000 and it was lower by 12,3% in comparison with 2014 and lower by
      20.4% in comparison with medianfor the years 2009-2014. The highest incidence
      (9.1 per 100 000) was registered in Kujawsko-pomorskie andthe lowest (3.3) - in
      Podkarpackie voivodeship. The highest incidence rate was observed among children
      aged 5years (48.3 per 100 000). Incidence in men (7.1 per 100 000) was higher
      than in women (4.4). In 2015, 12 peoplewere hospitalized due to mumps.
      Vaccination coverage of children aged 3 years in Poland in 2015 was 96,3%and it
      was lower by 0.7% in comparison with year 2014. CONCLUSIONS: Systematic execution
      of mumps vaccination in accordance with the National ImmunisationProgramme
      resulted in a significant decrease in the number of registered cases. Due to the
      high vaccinationcoverage further decline in the number of cases is expected.

PMID- 29181960
TI  - A starch, glycyrretinic, zinc oxide and bisabolol based cream in the treatment of
      chronic mild-to-moderate atopic dermatitis in children: a three-center, assessor
      blinded trial.
AB  - BACKGROUND: Atopic dermatitis (AD) is a very common chronic inflammatory and
      eczematous skin condition characterized by flares and remissions. Skin barrier
      alteration or dysfunction is the most relevant patogenetic factor. Topical
      corticosteroids are the mainstay treatment of AD, especially during flare
      periods. The daily use of emollients and moisturizers is also considered a
      relevant adjunctive strategy to improve skin barrier function and skin appearance
      in AD patients. Long-term use of topical corticosteroids is associated with
      important drawbacks and side effects. A corticosteroid-free cream containing
      starch, glycyrretinic acid, zinc oxide and bisabolol (DermamidTM; Difa Cooper,
      Caronno Pertusella, Varese, Italy) has been designed for the treatment of acute
      eczematous conditions like diaper dermatitis. However, this formulation could be
      particularly suitable also for AD. We evaluated in a three-center, assessor
      blinded prospective 6-week treatment trial the efficacy and tolerability of this
      cream in children with chronic mild-to-moderate atopic dermatitis. METHODS: A
      total of 30 children (mean age 5 years, 18 males and 12 females) with chronic
      mild to moderate AD, affecting face, lower and upper limbs or trunk, were
      enrolled after parents' written informed consent. Exclusion criteria were a
      condition of immunosuppression, acute flares or a positive history of allergy to
      one of the components of the cream. The primary outcome was the evolution total
      eczema severity score (TESS) calculated as the sum of the single eczema severity
      score for each body area involved. Single area Eczema Severity Score (ESS) was
      calculated assessing eczema, infiltration, lichenification and scraching lesions
      using a 4-point scale grade (with 0=no sign, and 4=severe sign). A secondary
      endpoint was the percentage of subjects reaching at least 50% of TESS reduction
      at week 6 in comparison with baseline. The TESS was evaluated at baseline and
      after 3 and 6 weeks of treatment (twice daily application) in an assessor-blind
      fashion. RESULTS: At baseline the mean (SD) TESS was 11.6 (4.7). TESS was reduced
      significantly (P=0.0001) to 5.7 (3) after 3 weeks (-51%), and to 3.0 (2.3) at
      week 6 (-74%). Similar reductions were observed for single area ESS values. The
      percentage of subjects with at least a >50% reduction of TESS value at the end of
      the study was 87%. The product was very well tolerated. Only for one patient a
      mild burning sensation at the application site was reported. All the subjects
      concluded the trial. CONCLUSIONS: This trial supports the efficacy and the
      tolerability of a corticosteroid-free cream containing starch, glycyrretinic acid
      and bisabolol in the treatment of chronic mild to moderate atopic dermatitis in
      children.

PMID- 29181961
TI  - Atypical causes of bacterial osteoarticular infections in immunocompetent
      children.
AB  - Caring for a child with an osteoarticular infection or considering the
      possibility of an osteoarticular infection in a child is one of the most common
      clinical dilemmas encountered by clinicians caring for children. In such a
      scenario, one most often considers infection with frequently encountered
      pathogens such as Staphylococcus aureus, Streptococcus pyogenes, Streptococcus
      pneumoniae or Kingella kingae. A large variety of opportunistic osteoarticular
      pathogens may be found in the immunosuppressed patient or the postoperative or
      post-trauma patient, due to breaches in the immune system and nosocomial or post
      traumatic exposure to multiple organisms. However, an enlarging spectrum of less
      commonly encountered bacterial pathogens is also increasingly appreciated in
      community-acquired osteoarticular infections in otherwise healthy children,
      particularly in this era of pneumococcal and Haemophilus influenzae serotype B
      immunization. Given the limitations of culture-based detection methods in
      osteoarticular infections and the potentially unique therapeutic and diagnostic
      approaches necessitated by some of these pathogens, an awareness of these
      infections is necessary for proper detection and management. This review will
      discuss less commonly encountered bacterial osteoarticular pathogens that may
      infect otherwise healthy children, with emphasis on the epidemiology, diagnosis
      and treatment of each.

PMID- 29181962
TI  - Unmet needs in children with diabetes: the role of basal insulin.
AB  - The goal of insulin therapy in people affected by type 1 diabetes mellitus
      consists in achieving an optimal metabolic control and so HbA1c levels below
      7.5%, according to the conclusions of relevant scientific studies. In any case it
      seems that this target is far from being achieved, mostly in the pediatric
      population. However, many important pharmacological, technological and cultural
      milestones have been placed both in therapy and management of insulin-dependent
      diabetes even if the gap between growing knowledge in these fields and its
      application in daily clinical practice appears still too wide. A fundamental
      component of these advancements concerns the design of new insulin basal
      analogues; molecules used to realize a basal-bolus model of therapy with MDI
      scheme. Degludec insulin has been recently approved for the pediatric utilization
      (aged 1 to 17 years). A registration trial for pediatric population (aged 6 to 17
      years) is in progress for glargine U-300 insulin. These two insulin types have
      different biochemical and pharmacological properties and they represent two
      different ways to achieve the ideal basal analogue. Insulin degludec and insulin
      glargine U-300 are the newest basal analogues and each of them has proper
      pharmacokinetic and pharmacodynamic characteristics. Their characteristics
      represent an effort to create the ideal solution. The aim of this review is to
      summarize the pharmacokinetic and pharmacodynamic properties of these new
      insulins, to list the most significant scientific findings regarding their
      pharmacology as well as clinical uses, with particular reference to the pediatric
      population in order to declare them to clinical experience and to report data on
      an initial experience with these analogues, especially with degludec insulin.
      Once again, evolution goes through the specialized training of the staff involved
      in the care of the diabetic patient and the constant education of the latter.

PMID- 29181963
TI  - Vitamin A- and E-based liposomal tear replacement in pediatric patients.

PMID- 29181964
TI  - Dexamethasone treatment for bacterial meningitis in children: what is the truth?

PMID- 29181965
TI  - A proposal of a follow-up protocol for children with neurogenic bladder.

PMID- 29181966
TI  - Bioelectrical impedance analysis: body composition in children and adolescents
      with Down syndrome.

PMID- 29181967
TI  - Legionellosis in Poland in 2015
AB  - OBJECTIVE: The aim of the study was to assess the epidemiological situation of
      legionellosis in Poland in2015 in comparison to the preceding years. MATERIAL AND
      METHODS: We reviewed data published in the annual bulletin: "Infectious diseases
      andpoisonings in Poland in 2015" and its prior versions along with the
      legionellosis case reports sent from Sanitary-Epidemiological Stations to the
      Department of Epidemiology of NIPH - NIH. RESULTS: In Poland, both two forms of
      legionellosis - Legionnaires' disease (a severe form of diseaseaccompanied by
      pneumonia) and Pontiac fever (mild, influenza-like form of infection) - are
      notifiable. In 2015,a total of 23 cases of Legionnaires' disease have been
      reported (there were no reports of Pontiac fever). Theannual incidence rate 0.060
      (per 100,000 population) slightly increased when compared to previous year as
      wellas to the median (incidence) for 2009-2013. The infections were reported in
      10 provinces, including five, whichin previous years usually did not register any
      cases; however, there is a number of provinces that did not identifyany LD cases
      in recent years. The incidence in males (0.097 per 100,000) was almost 4-times
      higher comparedto females (0.025). Except for one cluster of two, all cases were
      sporadic; All patients required hospitalization.The Sanitary Inspection reported
      four fatal cases - all men 43- 67 years/old. Eighteen cases were likely
      acquiredin the country, including a cluster of two cases linked with contaminated
      building water system. Four cases wereassociated with travels abroad (to Russia,
      Croatia, United Arab Emirates and USA) and in one case the exposureoccurred
      during the transport of goods (lorry driver). SUMMARY AND CONCLUSIONS: This study
      suggests, that legionellosis is likely under recognizedand under diagnosed in all
      provinces of the country. Geographical variations in incidence may reflect
      localdifferences in availability of laboratory tests for LD. Number of detected
      cases - without information on thenumber of laboratory tests performed - do not
      appear to be sufficient to fully assess the epidemiological situation.

PMID- 29181968
TI  - Growth Model of van der Waals Epitaxy of Films: A Case of AlN Films on Multilayer
      Graphene/SiC.
AB  - "Volmer-Weber" island nucleation and step-flow growth model are the classical
      processes of the conventional epitaxy of films. However, a growth model of van
      der Waals epitaxy (vdWE) of films is still not very well-documented. Here, we
      present an example of vdWE of AlN films on multilayer graphene (MLG)/SiC by
      hydride vapor phase epitaxy at a high temperature of 1100  degrees C and reveal
      the orientation relationship of AlN, MLG, and SiC as (0001)[1-100]AlN||(0001)[1
      100]MLG||(0001)[11-20]SiC, which suggests that the vdWE heterointerface is not an
      usual covalent bond and no excessive strain during the growth process owing to
      the incommensurate in-plane lattices. Remarkably, zigzag cracks are formed
      because of the anisotropy of strain after the films are cooled down to room
      temperature, indicating that the growth model of vdWE is different from that of
      conventional epitaxy. It is a layer-by-layer epitaxy, and a planar substrate
      without a miscut angle is essential for obtaining single-crystalline films.
      Additionally, the films can be transferred to foreign substrates by direct
      mechanical exfoliation without any stressor layer. An ultraviolet photosensor
      device illustrates an example of III-nitride heterogeneous integration
      application. Our work demonstrates an excellent step toward the vdWE of varieties
      of compound films on 2D materials for the applications of transferrable
      heterogeneous integration in future.

PMID- 29181969
TI  - DNAzyme Based Nanomachine for in Situ Detection of MicroRNA in Living Cells.
AB  - The capability of in situ detection of microRNA in living cells with signal
      amplification strategy is of fundamental importance, and it will open up a new
      opportunity in development of diagnosis and prognosis of many diseases. Herein we
      report a swing DNA nanomachine for intracellular microRNA detection. The surfaces
      of Au nanoparticles (NPs) are modified by two hairpin DNA. We observe that one
      DNA (MB2) will open its hairpin structure upon partial hybridization with target
      miR-21 after entering into cells, and the other part of its hairpin structure
      could further react with the other hairpin DNA (MB1) to form a Zn2+-specific
      DNAzyme. This results in the disruption of MB1 through shearing action and the
      release of fluorescein Cy5. To provide an intelligent DNA nanomachine, MB2 is
      available again with the shearing action to bind with MB1, which provides
      effective signal amplification. This target-responsive, DNA nanomachine-based
      method showed a detection limit of 0.1 nM in vitro, and this approach could be an
      important step toward intracellular amplified detection and imaging of various
      analytes in living cells.

PMID- 29181970
TI  - Catalyst-Controlled Structural Divergence: Selective Intramolecular 7-endo-dig
      and 6-exo-dig Post-Ugi Cyclization for the Synthesis of Benzoxazepinones and
      Benzoxazinones.
AB  - Metal catalyzed post-Ugi cyclization of bis-amides is reported in this study.
      Exposure of bis-amides to Pd(II) catalyst triggered the formation of seven
      membered benzoxazepinones. This investigation established that changing the
      catalyst to a Echavarren's gold(I) turned off cyclization to seven member ring
      and turned on 6-exo-dig annulations to afford family of six-membered
      benzoxazinones. To support the proposed mechanisms, quantum chemical based
      density functional theory calculations have been performed and validated. This
      novel method obtained molecular complexity up to four modular inputs and
      divergence of two different skeletons. 2D NMR spectroscopic techniques and single
      crystal X-ray diffraction established the proposed structures.

PMID- 29181971
TI  - Synthesis of Vinyl-, Allyl-, and 2-Boryl Allylboronates via a Highly Selective
      Copper-Catalyzed Borylation of Propargylic Alcohols.
AB  - An efficient methodology for the synthesis of vinyl-, allyl-, and (E)-2-boryl
      allylboronates from propargylic alcohols via Cu-catalyzed borylation under mild
      conditions is reported. In the presence of commercially available Cu(OAc)2 or
      Cu(acac)2 and Xantphos, the reaction affords the desired products in up to 92%
      yield with a broad substrate scope (43 examples). Isolation of an allenyl
      boronate as the reaction intermediate suggests that an insertion-elimination-type
      reaction, followed by borylcupration, is involved in the borylation of
      propargylic alcohols.

PMID- 29181972
TI  - Fully Elastic Conductive Films from Viscoelastic Composites.
AB  - We investigated, for the first time, the conditions where a thermoplastic
      conductive composite can exhibit completely reversible stretchability at high
      elongational strains (epsilon = 1.8). We studied a composite of Au nanosheets and
      a polystyrene-block-polybutadiene-block-polystyrene block copolymer as an
      example. The composite had an outstandingly low sheet resistance (0.45 Omega/sq).
      We found that when a thin thermoplastic composite film is placed on a relatively
      thicker chemically cross-linked elastomer film, it can follow the reversible
      elastic behavior of the bottom elastomer. Such elasticity comes from the
      restoration of the block copolymer microstructure. The strong adhesion of the
      thermoplastic polymer to the metallic fillers is advantageous in the fabrication
      of mechanically robust, highly conductive, stretchable electrodes. The chemical
      stability of the Au composite was used to fabricate high luminescence,
      stretchable electrochemiluminescence displays with a conventional top-bottom
      electrode setup and with a horizontal electrode setup.

PMID- 29181973
TI  - Selective Separation and Preconcentration of Scandium with Mesoporous Silica.
AB  - Separation and preconcentration of scandium (Sc) were successfully achieved using
      a mesoporous silica support that showed good selectivity for this element.
      Unmodified mesoporous silica materials were used as an extracting medium in a
      solid-liquid extraction (SLE) process. Selectivity, extraction capacity, kinetics
      of extraction, and reusability under acidic conditions were investigated. The
      results demonstrate the potential of unmodified mesoporous silica materials for
      the selective separation and preconcentration of Sc. As no chelating ligand was
      grafted on the silica surface, which is often the case for most solid-phase
      extraction media for metal-ion separation, the experimental data allow us to
      hypothesize that the accessible silanols on the material surface are responsible
      for the selective Sc extraction. This interesting feature would drastically
      decrease the cost of solid-liquid extraction systems by using unmodified
      mesoporous silica materials. Moreover, a leachate solution obtained from a real
      rare-earth element ore was used to determine the performances of the proposed
      materials in a packed column configuration. The maximum Sc adsorption on the
      silica material surfaces is moderate (1 mg/g), but it is balanced by a great
      concentration factor (more than 100 times). The extraction performances are
      potentially promising, both in terms of selectivity and preconcentration, under
      the acidic conditions tested.

PMID- 29181974
TI  - ATP-Activatable Photosensitizer Enables Dual Fluorescence Imaging and Targeted
      Photodynamic Therapy of Tumor.
AB  - Targeted delivery of intracellular stimuli-activatable photosensitizers (PSs)
      into tumor cells to achieve selective imaging and on-demand photodynamic therapy
      (PDT) of tumors has provided a vital opportunity for precise cancer diagnosis and
      therapy. In this paper, we report a tumor targeting and adenosine triphosphate
      (ATP)-activatable nanophotosensitizer Apt-HyNP/BHQ2 by modifying hybrid micellar
      nanoparticles with both nucleolin-targeting aptamer AS1411 and quencher BHQ2
      labeled ATP-binding aptamer BHQ2-ATP-apt. We demonstrated that both of the
      fluorescence emissions at 555 and 627 nm were quenched by BHQ2 in Apt-HyNP/BHQ2,
      resulting in low PDT capacity. After selective entry into tumor cells through
      nucleolin-mediated endocytosis, the high concentration of intracellular ATP could
      bind to BHQ2-ATP-apt and trigger Apt-HyNP/BHQ2 dissociation, leading to turning
      "on" both fluorescence and PDT. The "off-on" fluorescence emissions at both 555
      and 627 nm were successfully applied for dual color fluorescence imaging of
      endogenous ATP levels and real-time monitoring of intracellular activation of Apt
      HyNP/BHQ2 in tumor cells. Moreover, imaging-guided precise PDT of tumors in
      living mice was also demonstrated, allowing for selective ablation of tumors
      without obvious side effects. This study highlights the potential of using a
      combination of tumor-targeting and ATP-binding aptamers to design ATP-activatable
      PSs for both fluorescence imaging and imaging-guided PDT of tumors in vivo.

PMID- 29181975
TI  - Alteration in MicroRNA Expression Governs the Nature and Timing of Cellular Fate
      Commitment.
AB  - In the central nervous system, the expression level of transcriptional repressor
      Hes1 (hairy and enhancer of split-1) tightly controls the alternative cell fate
      commitment during differentiation as well as the time required for such cellular
      transitions. A microRNA, miR-9, that interacts with Hes1 in a mutually
      antagonistic manner, influences both the process of lineage specification and
      timing of differentiation significantly, but the impact of the miR-9 in guiding
      these events still remains poorly understood. Here, we proposed a stochastic
      mathematical model of the miR-9/Hes1 double-negative feedback interaction network
      that at the outset shows how alternative cell fate such as quiescence,
      progenitor, and neuronal states can be accomplished through fine-tuning the Hes1
      dynamics by altering the expression level of miR-9. The model simulations further
      foretell a correlated variation of the period of oscillation of Hes1, and the
      time delay observed between Hes1 mRNA and protein as the transcription rate of
      miR-9 increases during the neural progenitor state attainment. Importantly, the
      model simulations aided by the systematic sensitivity analysis predict that the
      timing of differentiation to the neuronal state crucially depends on the negative
      regulators (miR-9 and Hes6) of the Hes1. Our results indicate that miR-9/Hes1
      interaction network can be effectively exploited for an efficient and well-timed
      neuronal transformation.

PMID- 29181976
TI  - Effect of Low Temperature on Charge Transport in Operational Planar and
      Mesoporous Perovskite Solar Cells.
AB  - Low-temperature optoelectrical studies of perovskite solar cells using MAPbI3 and
      mixed-perovskite absorbers implemented into planar and mesoporous architectures
      reveal fundamental charge transporting properties in fully assembled devices
      operating under light bias. Both types of devices exhibit inverse correlation of
      charge carrier lifetime as a function of temperature, extending carrier lifetimes
      upon temperature reduction, especially after exposure to high optical biases.
      Contribution of bimolecular channels to the overall recombination process should
      not be overlooked because the density of generated charge surpasses trap-filling
      concentration requirements. Bimolecular charge recombination coefficient in both
      device types is smaller than Langevin theory prediction, and its mean value is
      independent of the applied illumination intensity. In planar devices, charge
      extraction declines upon MAPbI3 transition from a tetragonal to an orthorhombic
      phase, indicating a connection between the trapping/detrapping mechanism and
      temperature. Studies on charge extraction by linearly increasing voltage further
      support this assertion, as charge carrier mobility dependence on temperature
      follows multiple-trapping predictions for both device structures. The
      monotonously increasing trend following the rise in temperature opposes the
      behavior observed in neat perovskite films and indicates the importance of
      transporting layers and the effect they have on charge transport in fully
      assembled solar cells. Low-temperature phase transition shows no pattern of
      influence on thermally activated electron/hole transport.

PMID- 29181977
TI  - Air-Stable Transparent Silver Iodide-Copper Iodide Heterojunction Diode.
AB  - Transparent AgI-CuI heterojunctions with high rectifying diode behavior were
      prepared via vapor-phase iodization of metal thin films on transparent conducting
      oxide substrates. At room temperature, Ag and Cu metal thin films were quickly
      transformed into the transparent and well-crystallized beta-phase of AgI and the
      gamma-phase of CuI, respectively. The AgI and CuI films exhibited n-type and p
      type semiconductor properties, respectively, with wide band gaps. The
      heterojunctions were obtained by applying the CuI film to the AgI film in a
      sequential iodization process. AgI compounds generally have poor air-stability
      under light, making them suboptimal for use in electronic applications. Here, we
      used a CuI top layer to inhibit the photodecomposition of the AgI bottom layer,
      resulting in an air-stable and smooth AgI-CuI film. We also propose a simple
      patterning method for the AgI-CuI layer using selective decomposition of AgI
      without the need for lithography equipment or toxic chemicals. Although there is
      metal ion exchange between the two layers, each layer has a different chemical
      composition and crystal structure; therefore, the AgI-CuI heterojunction exhibits
      pn-diode behavior with a rectifying ratio of 9.4 * 104, which is comparable to
      that of other transparent pn-diodes. These findings open a new path for
      electronic application of AgI materials.

PMID- 29181978
TI  - Improving the Secretion Yield of the beta-Galactosidase Bgal1-3 in Pichia
      pastoris for Use as a Potential Catalyst in the Production of Prebiotic-Enriched
      Milk.
AB  - In this study, three kinds of milk were treated with the beta-galactosidase Bgal1
      3 (4 U/mL), resulting in 7.2-9.5 g/L galactooligosaccharides (GOS) at a lactose
      conversion of 90-95%. Then, Bgal1-3 was secreted from Pichia pastoris X33 under
      the direction of an alpha-factor signal peptide. After cultivation for 144 h in a
      flask culture with shaking, the extracellular activity of Bgal1-3 was 4.4 U/mL.
      Five more signal peptides (HFBI, apre, INU1A, MF4I, and W1) were employed to
      direct the secretion, giving rise to a more efficient signal peptide, W1 (11.2
      U/mL). To further improve the secretion yield, recombinant strains harboring two
      copies of the bgal1-3 gene were constructed, improving the extracellular activity
      to 22.6 U/mL (about 440 mg/L). This study successfully constructed an engineered
      strain for the production of the beta-galactosidase Bgal1-3, which is a promising
      catalyst in the preparation of prebiotic-enriched milk.

PMID- 29181979
TI  - Ytterbium-Catalyzed Hydroboration of Aldehydes and Ketones.
AB  - The well-defined heavy rare-earth ytterbium iodide complex 1 (L2YbI) has been
      successfully employed as an efficient catalyst for the hydroboration of a wide
      range of aldehydes and ketones with pinacolborane (HBpin) at room temperature.
      The protocol requires low catalyst loadings (0.1-0.5 mol %) and proceeds rapidly
      (>99% conversion in <10 min). Additionally, catalyst 1 shows a good functional
      group tolerance even toward the hydroxyl and amino moieties and displays
      chemoselective hydroboration of aldehydes over ketones under mild conditions.

PMID- 29181980
TI  - Palladium-Catalyzed Domino Alkenylation/Amination/Pyridination Reactions of 2
      Vinylanilines with Alkynes: Access to Cyclopentaquinolines.
AB  - A novel domino oxidative annulation of 2-vinylanilines with internal alkynes was
      developed to constitute a rare class of cyclopentaquinoline derivatives. This
      transformation encompasses four sigma bonds formation, one quaternary carbon
      center construction, and pyridination steps in one pot under identical
      conditions, which fascinatingly increases the molecular complexity from easily
      available starting materials.

PMID- 29181981
TI  - Comprehensive Proteomic Investigation of Ebf1 Heterozygosity in Pro-B Lymphocytes
      Utilizing Data Independent Acquisition.
AB  - Early B cell factor 1 (EBF1) is one of the key transcription factors required for
      orchestrating B-cell lineage development. Although studies have shown that Ebf1
      haploinsufficiency is involved in the development of leukemia, no study has been
      conducted that characterizes the global effect of Ebf1 heterozygosity on the
      proteome of pro-B lymphocytes. Here, we employ both data independent acquisition
      (DIA) and shotgun data dependent acquisition (DDA) workflows for profiling
      proteins that are differently expressed between Ebf1+/+ and Ebf1+/- cells. Both
      DDA and DIA were able to reveal the downregulation of the EBF1 transcription
      factor in Ebf1+/- pro-B lymphocytes. Further examination of differentially
      expressed proteins by DIA revealed that, similar to EBF1, the expression of other
      B-cell lineage regulators, such as TCF3 and Pax5, is also downregulated in Ebf1
      heterozygous cells. Functional DIA analysis of differentially expressed proteins
      showed that EBF1 heterozygosity resulted in the deregulation of at least eight
      transcription factors involved in lymphopoiesis and the deregulation of key
      proteins playing crucial roles in survival, development, and differentiation of
      pro-B lymphocytes.

PMID- 29181982
TI  - Catalytic Asymmetric Cascade Using Spiro-Pyrrolidine Organocatalyst: Efficient
      Construction of Hydrophenanthridine Derivatives.
AB  - A newly developed SPD (spiro-pyrrolidine) organocatalyst has been demonstrated to
      enable an asymmetric aza-Michael/Michael/aldol cyclization cascade, in which two
      six-membered rings (B/C) and three stereocenters have been constructed in a
      catalytic one-step process. It is so far the most efficient method for
      construction of hydrophenanthridine derivatives featuring high
      enantioselectivity. The trans- or cis-fused B/C-rings can be selectively
      assembled in a substrate-controlled manner. Moreover, this cascade could magnify
      to gram scale without loss of enanioselectivity.

PMID- 29181983
TI  - Synthesis of 4-(Trifluoromethyl)cyclopentenones and 2-(Trifluoromethyl)furans by
      Reductive Trifluoroacetylation of Ynones.
AB  - Reductive introduction of a fluorine-containing carbon block to readily available
      conjugated ynones, followed by intramolecular cyclization, successfully gave the
      corresponding trifluoromethylated cyclopentenones or trifluoromethylated furans
      in good yields through a simple two-step protocol. The key compound in carbon
      carbon bond formation by magnesium-promoted reduction is ethyl trifluoroacetate,
      which has been rarely used as a fluorine-containing carbon source, especially to
      electron-deficient carbon atoms in organic synthesis.

PMID- 29181984
TI  - From Positive to Negative Zero-Field Splitting in a Series of Strongly
      Magnetically Anisotropic Mononuclear Metal Complexes.
AB  - A series of mononuclear [M(hfa)2(pic)2] (Hhfa = 1,1,1,5,5,5-hexafluoro-2,4
      pentanedione; pic = 4-methylpyridine; M = FeII, CoII, NiII, ZnII) compounds were
      obtained and characterized. The structures of the complexes have been resolved by
      single-crystal X-ray diffraction, indicating that, apart from the zinc
      derivative, the complexes are in a trans configuration. Moreover, a dramatic
      lenghthening of the Fe-N distances was observed, whereas the nickel(II) complex
      is almost perfectly octahedral. The magnetic anisotropy of these complexes was
      thoroughly studied by direct-current (dc) magnetic measurements, high-field
      electron paramagnetic resonance, and infrared (IR) magnetospectroscopy: the
      iron(II) derivative exhibits an out-of-plane anisotropy (DFe = -7.28 cm-1) with a
      high rhombicity, whereas the cobalt(II) and nickel(II) complexes show in-plane
      anisotropy (DCo ~ 92-95 cm-1; DNi = 4.920 cm-1). Ab initio calculations were
      performed to rationalize the evolution of the structure and identify the excited
      states governing the magnetic anisotropy along the series. For the iron(II)
      complex, an out-of-phase alternating-current (ac) magnetic susceptibility signal
      was observed using a 0.1 T dc field. For the cobalt(II) derivative, the ac
      magnetic susceptibility shows the presence of two field-dependent relaxation
      phenomena: at low field (500 Oe), the relaxation process is beyond single-ion
      behavior, whereas at high field (2000 Oe), the relaxation of magnetization
      implies several mechanisms including an Orbach process with Ueff = 25 K and
      quantum tunneling of magnetization. The observation by MU-SQUID magnetization
      measurements of hysteresis loops of up to 1 K confirmed the single-ion-magnet
      behavior of the cobalt(II) derivative.

PMID- 29181985
TI  - Henrik S Thomsen: New Chief Editor of Acta Radiologica.

PMID- 29181986
TI  - Disproportionate fluid sign as an aid in diagnosing high-grade bursal-sided
      supraspinatus tendon tear.
AB  - Background Deep, high-grade bursal-sided supraspinatus tendon tears are sometimes
      preoperatively misinterpreted as full-thickness tears on shoulder magnetic
      resonance imaging (MRI). Purpose To determine the usefulness of disproportionate
      fluid sign for differentiating high-grade bursal-sided partial-thickness tears
      from full-thickness tears on conventional MRI. Material and Methods Preoperative
      MRIs of 198 patients with arthroscopically confirmed high-grade bursal-sided
      partial-thickness tears and full-thickness tears were independently reviewed by
      two readers on two occasions. The presence of high-grade bursal-sided partial
      thickness tears with a confidence level using a five-point grading scale was
      assessed based on tear depth alone and also in combination with disproportionate
      fluid sign, defined as a prominent subdeltoid or subacromial-subdeltoid bursal
      fluid distension with a relative paucity of effusion in the glenohumeral joint.
      The sensitivity, specificity, accuracy, and area under the receiver operating
      characteristic curve (AUC) were calculated, as well as inter-observer
      reliability. Results The disproportionate fluid sign was identified in 60/74
      (81.2%) bursal-sided partial-thickness tears and 9/124 (7.5%) full-thickness
      tears. The sensitivity and accuracy of the diagnosis of bursal-sided tear were
      higher when disproportionate fluid sign was used in conjunction with the tear
      depth, compared with tear depth alone ( P < 0.001). There was excellent inter
      observer agreement for disproportionate fluid sign and deep bursal-sided tear.
      The AUCs were significantly higher in combination with disproportionate fluid
      sign. Conclusion The disproportionate fluid sign indicates the presence of a
      deep, high-grade bursal-sided partial-thickness tear, which can be misinterpreted
      as a full-thickness tear. Thus, it can provide greater diagnostic assistance to
      less-experienced radiologists and clinicians.

PMID- 29181987
TI  - New co-editor: Neuroradiology.

PMID- 29181988
TI  - Diagnostic performances and interobserver agreement according to observer
      experience: a comparison study using three guidelines for management of thyroid
      nodules.
AB  - Background The differences regarding categorization of thyroid nodules among
      different guidelines may affect the diagnostic performances and agreement among
      observers. Purpose To compare the diagnostic performances and agreements between
      observers with various degree of experience when applying different guidelines
      for stratifying thyroid nodules using suspicious ultrasonography (US) features.
      Material and Methods This retrospective study included 370 thyroid nodules (>=10
      mm). Four observers, grouped as experienced and inexperienced, evaluated the US
      features and made final assessments according to the Kim criteria, Thyroid
      Imaging Reporting and Data System (TIRADS) by Kwak et al., and the 2015 American
      Thyroid Association (ATA) guideline. Diagnostic performances and agreements among
      the two groups were compared. Results The Kim criteria shows higher specificity
      with significantly lower sensitivity when compared to TIRADS and the 2015 ATA
      guideline (all P < 0.001), regardless of the level of experience. The experienced
      group showed significantly higher specificity with the Kim criteria and the 2015
      ATA guideline compared to the inexperienced group ( P < 0.001), and the
      inexperienced group showed significantly higher sensitivity using the Kim
      criteria ( P = 0.002). The experienced group showed significantly higher
      agreement than the inexperienced group when using TIRADS while higher agreement
      was seen when using the 2015 ATA guideline for the inexperienced group. Agreement
      was not significantly different for the Kim criteria according to observer
      experience. Conclusion The diagnostic performances and agreements show
      significant differences in risk stratification of thyroid nodules according to
      the three guidelines using suspicious US features and the level of experience of
      the observer.

PMID- 29181989
TI  - Fourth update on CT angiography of coronary stents: in vitro evaluation of 24
      novel stent types.
AB  - Background Non-invasive evaluation of coronary stent patency by coronary computed
      tomography angiography (cCTA) remains challenging. Multiple studies showed that
      CT technology but also individual stent design strongly influence the
      assessability of coronary stents by cCTA. Purpose To expand the available data on
      cCTA characteristics of coronary stents by 24 novel types to help interpreting
      examinations of patients after stent placement and selecting which stents are
      suitable for assessment by cCTA. Material and Methods Twenty-four novel coronary
      stents (17 cobalt-chromium, six stainless-steel, one platinum-chromium) were
      examined in a coronary phantom. Standard cCTA parameters with stent-specific
      algorithms were used. Image quality was quantified for each stent using
      established parameters (in-stent attenuation alteration and visible lumen
      diameter). Results Most stents (n = 14) showed lumen visibilities of 45-55%. No
      severe restriction of lumen visibility (>60%) was found. The majority of stents
      (n = 13) caused only small intraluminal attenuation deviations and no severe
      alterations (>20%) were found. When grouped by manufacturing material, no
      significant differences were found between cobalt-chromium and stainless-steel
      with identical mean visible diameters (1.52 +/- 0.17 mm vs. 1.52 +/- 0.13 mm) and
      comparable attenuation alterations (35.04 +/- 16.56 HU vs. 21.25 +/- 14.60 HU).
      The only platinum-chromium stent showed a smaller visible diameter (1.23 mm) and
      higher attenuation alteration (41.70 HU), but was also deemed to be assessable by
      cCTA. Conclusion All 24 novel evaluated stents are eligible for non-invasive
      evaluation by cCTA without significant differences between cobalt-chromium and
      stainless-steel stents. This updated catalogue of CT appearances of current
      coronary stents may serve as reference when taking care of patients with stents
      in need of coronary imaging.

PMID- 29181990
TI  - Is Commissural region tear an Achilles' heel of the Trifecta aortic
      bioprosthesis?

PMID- 29181991
TI  - Chest wall resection and reconstruction for Rosai-Dorfman disease masquerading as
      a chest wall sarcoma.
AB  - Rosai-Dorfman disease (RDD) is a rare benign histiocytic proliferative disease
      that can present as a pseudotumour of soft tissue. We describe the first chest
      wall resection and reconstruction.

PMID- 29181992
TI  - The significance of the pharyngeal veins during carotid endarterectomy:
      description of an anatomical triangle.
AB  - Injuries to the hypoglossal and vagus nerves are the most commonly reported
      injuries during carotid endarterectomy. While unilateral single nerve injury is
      usually well tolerated, bilateral or combined nerve injuries can pose a serious
      threat to life. This study aims to increase awareness of the inferior pharyngeal
      vein, which usually passes posterior to the internal carotid artery but sometimes
      crosses anterior to it. Injury to either or both hypoglossal and vagus nerves can
      occur during control of unexpected haemorrhage from the torn and retracted edges
      of the inferior pharyngeal vein. We recommend careful ligation and division of
      this vein. In addition, we observed in 9 (17.3%) of the 52 operations that the
      pharyngeal vein formed a triangle with the vagus and hypoglossal nerves when it
      passes anterior to the internal carotid artery.

PMID- 29181994
TI  - Urachal remnant causing umbilical in-drawing during micturition.
AB  - The urachus is a vestigial remnant of the allantois, which is normally
      obliterated during fetal life to become the median umbilical ligament, which runs
      between the urinary bladder and umbilicus in adults. Failure of obliteration
      leaves a tubular urachal remnant, which may present with disease. We report a
      unique case of a urachal remnant causing umbilical pain and in-drawing on
      micturition in a nine-year-old boy. There was no urine discharge from the
      umbilicus and in-drawing did not occur on defecation. His urinary stream was
      normal. High frequency ultrasonography revealed a thick band with a narrow,
      anechoic, fluid filled central channel. Exploration via an infraumbilical
      curvilinear incision identified a thick urachal band that could be traced to the
      dome of the bladder. This was excised flush with the bladder. The patient remains
      well at nine months following surgery with complete cessation of symptoms.

PMID- 29181993
TI  - 'Reverse guide wire' technique for placement of anterior column/superior pubic
      ramus screw in pelvis and acetabular surgery.

PMID- 29181995
TI  - The effect of rectal washout on local recurrence following rectal cancer surgery.
AB  - Introduction Local recurrence after surgery for rectal cancer is associated with
      significant morbidity and debilitating symptoms. Intraoperative rectal washout
      has been linked to a reduction in local recurrence but there is no conclusive
      evidence. The aim of this study was to evaluate whether performing rectal washout
      had any effect on the incidence of local recurrence in patients undergoing
      anterior resection for rectal cancer in the context of the current surgical
      management. Methods A total of 395 consecutive patients who underwent anterior
      resection with or without rectal washout for rectal cancer between January 2003
      and July 2009 at a high volume single institution were analysed retrospectively.
      A standardised process for performing washout was used and all patients had
      standardised surgery in the form of total mesorectal excision. Neoadjuvant and
      adjuvant therapy was used on a selected basis. Patients were followed up for five
      years and local recurrence rates were compared in the two groups. Results Of the
      395 patients, 297 had rectal washout and 98 did not. Both groups were well
      matched with regard to various important clinical, operative and
      histopathological characteristics. Overall, the local recurrence rate was 5.3%.
      There was no significant difference in the incidence of local recurrence between
      the washout group (5.7%) and the no washout group (4.1%). Conclusions Among our
      cohort of patients, there was no statistical difference in the incidence of local
      recurrence after anterior resection with or without rectal washout. This suggests
      that other factors are more significant in the development of local recurrence.

PMID- 29181996
TI  - Choledochal cyst of the proximal cystic duct: a taxonomical and therapeutic
      conundrum.
AB  - Isolated choledochal cysts involving the cystic duct are rare. We present a case
      of a choledochal cyst involving only the proximal cystic duct, and discuss the
      taxonomic and therapeutic challenges. There is a need for a clearly defined
      classification system for these cysts as they may be categorised as either type
      II or type VI cysts. The optimal treatment remains debatable, with some authors
      recommending a bilioenteric reconstruction owing to the wide cystic duct-bile
      duct junction. However, we suggest that a cholecystectomy should be performed
      with examination of the specimen and frozen section in case of any abnormality
      rather than upfront bile duct excision. In addition, given the rarity of this
      condition and the paucity of long-term data, we recommend meticulous follow-up
      for development of any malignancy.

PMID- 29181997
TI  - Tension band wire stabilisation: an aid to femoral intramedullary nail fixation.

PMID- 29181998
TI  - A technique for K-wire assisted closed reduction and percutaneous screw fixation
      of phalangeal fractures.

PMID- 29181999
TI  - The effect of non-steroidal anti-inflammatory drugs on severity of acute
      pancreatitis and pancreatic necrosis.
AB  - Introduction Acute pancreatitis (AP) is a common emergency presentation and can
      be disabling. There is significant morbidity and mortality associated with AP,
      and it places a considerable burden on the healthcare system. Non-steroidal anti
      inflammatory drugs (NSAIDs) have been shown to have a protective effect in some
      elective contexts. This retrospective study aimed to evaluate the effect of
      NSAIDs on the course of AP and the severity of the disease. Methods A
      retrospective analysis was carried out of 324 patients admitted as an emergency
      with a diagnosis of AP to two UK hospitals. Patients were divided into two
      groups: those already taking NSAIDs for other co-morbidities and those not taking
      NSAIDs. Variables compared included: admission to a high dependency or intensive
      care unit; pancreatic necrosis; pseudocyst development; need for surgery; serum
      inflammatory markers; modified early warning scores on days 1, 3 and 5; length of
      stay; and mortality. Results Patients not taking NSAIDs were more likely to have
      a C-reactive protein level of >=150mg/l (p=0.007). Patients in the NSAID group
      experienced less pancreatic necrosis (p=0.019) and lower rates of pseudocyst
      formation (p=0.010). Other variables showed no difference between the two groups,
      specifically length of stay and mortality. Conclusions Routine NSAID use may
      exert a protective effect on the development of AP, its severity, and
      complications. Therapeutic use of NSAIDs in acute presentations with pancreatitis
      should be further evaluated.

PMID- 29182000
TI  - Colossal pilomatrixoma.
AB  - We describe the largest reported case of pilomatrixoma in the literature. While
      pilomatrixomas typically present as small soft-tissue nodules of the head, neck
      and upper extremities, they can also present as much larger masses in atypical
      locations. When they present in their usual size, pilomatrixomas have typical
      imaging features and can be correctly diagnosed with imaging studies before
      histological confirmation. Their clinical and imaging diagnosis become
      challenging when they are very large, as in our case. A giant pilomatrixoma
      should also be considered for paediatric patients presenting with a large
      subcutaneous soft-tissue mass.

PMID- 29182001
TI  - Surgical resection of a massive primary mediastinal liposarcoma with cervical
      extension.
AB  - A 73-year-old man was referred for surgical excision of a massive mediastinal and
      cervical liposarcoma following neoadjuvant chemotherapy. Surgery was performed
      via a cervical incision, sternotomy and right posterolateral thoracotomy. The
      tumour arose from the oesophagus, which underwent extensive dissection and was
      oversewn with pleura after tumour resection. Histology confirmed a completely
      excised grade 2 de-differentiated liposarcoma with complete macroscopic excision.
      The patient made an excellent recovery. Oesophageal liposarcomas are rare and,
      unlike in this case, often extend intraluminally, necessitating oesophagectomy.
      To our knowledge, this is the largest such tumour found in the literature.

PMID- 29182002
TI  - Acute hand injury splinting - the good, the bad and the ugly.
AB  - Injuries to the hand comprise 20% of all emergency department attendances, with
      an estimated annual treatment cost of over L100 million in the UK. The initial
      assessment and management of hand injuries is usually undertaken by junior staff,
      many of whom have little or no training or experience in splinting hand
      fractures. In the Department of Orthopaedic Hand Surgery, Morriston Hospital, we
      regularly observe patients presenting to the specialist hand fracture clinics
      having had initial management that shows no appreciation for the treatment
      objectives or the safe positions for splinting. This article aims to provide
      guidance for frontline staff on the management of hand fractures, with particular
      emphasis on the appropriate nonoperative care to avoid any unnecessary morbidity.

PMID- 29182004
TI  - SIPRI yearbook 2017: armaments, disarmament and international security.

PMID- 29182003
TI  - Modification, validation and implementation of a protocol for post-thyroidectomy
      hypocalcaemia.
AB  - Introduction The management of post-thyroidectomy hypocalcaemia should facilitate
      early discharge, and reduce risks of hypocalcaemia, readmission and treatment
      related hypercalcaemia. This paper describes the implementation, evaluation and
      revision a protocol for the optimal management of this condition. Methods Day 1
      parathyroid hormone (PTH) measurements in addition to calcium measurements were
      commenced following review of the unit's outcomes and literature on post
      thyroidectomy hypocalcaemia. Outcomes from a three-year cohort of patients
      undergoing thyroid surgery helped amend this protocol (revision 1) to reduce
      biochemical tests, stipulate the need, nature and dose of vitamin D/calcium
      supplements, and encourage early discharge. This was further validated over seven
      months to assess compliance, episodes of hyper and/or hypocalcaemia after
      discharge, readmissions and need for treatment changes. Further revisions were
      made (revision 2) and implemented. Results The temporary and long-term
      postoperative hypocalcaemia rates were 29.1% and 3.2% respectively. Repeat
      calcium measurements on the first day altered management in only 1.4% of cases.
      The revised protocol was adhered to in 90% of cases. One patient had
      hypocalcaemia (due to non-compliance) and one had hypercalcaemia. Revision 2
      involved reducing the dose of calcium. Conclusions This is a good example of a
      unit protocol for post-thyroidectomy hypocalcaemia being developed and modified
      on the basis of the literature and local experience. Day 1 PTH and calcium levels
      determine the need for treatment and frequency of follow-up visits, facilitate
      early discharge, reduce risk of over and/or undertreatment, and are good
      indicators of permanent hypocalcaemia.

PMID- 29182005
TI  - IL-1beta gene polymorphism and serum levels in a Tunisian population with acute
      heart failure.
AB  - AIM: The aim of this study was to explore the relationship between IL-1beta-31T/C
      polymorphism and serum levels of IL-1beta and the risk of acute heart failure
      (AHF). METHODS: A total of 320 dyspnea patients (160 with AHF and 160 without
      AHF) and 100 healthy subjects were included in this study. IL-1beta genotyping
      was performed by PCR-restriction fragment length polymorphism technique. RESULTS:
      Concentration of IL-1beta was significantly higher in patients with heart failure
      (HF) compared with non-HF and control groups. Results of the distribution of IL
      1beta-31T/C genotypes and allele frequencies did not show any significant
      difference between the three groups. Serum levels of IL-1beta were found to be
      higher among TT genotype than TC and CC genotype. CONCLUSION: IL-1beta levels may
      be useful for the evaluation of diagnosis in acutely decompensated HF.

PMID- 29182006
TI  - Intimacy, intercourse and adjustments: Experiences of sexual life of a group of
      people with physical disabilities in South Africa.
AB  - There is a growing recognition of the sexual and reproductive rights of people
      with disabilities, and since the World Health Organisation's World Report on
      Disability, increased international attention has been given to these issues.
      Past research, however, suggests that this group encounter barriers to sexual and
      reproductive rights, which are both physical and attitudinal. Against this
      backdrop, this article employs a sequential mixed qualitative methodology to
      explore the practical and subjective experiences of 13 people with physical
      disabilities in South Africa, with regard to their sexual lives and experiences
      of sexuality. These experiences were marked by concerns about their 'fitness' as
      sexual beings and indicated that social forces were key in shaping their
      expectations for their own sexual life.

PMID- 29182007
TI  - Approaching recovery from myalgic encephalomyelitis and chronic fatigue syndrome:
      Challenges to consider in research and practice.
AB  - There are unique methodological challenges to studying and assessing recovery in
      myalgic encephalomyelitis and chronic fatigue syndrome. This study explored these
      challenges through interviewing 13 physicians who treat myalgic encephalomyelitis
      and chronic fatigue syndrome. Our deductive thematic analysis produced four
      themes to consider when approaching recovery: lifespan differences in the illness
      experience; the heterogeneity of myalgic encephalomyelitis and chronic fatigue
      syndrome-case definitions, etiological stance, and misdiagnosis; patient follow
      up and selection bias; and assessment logistics. We discuss how researchers and
      clinicians can use these considerations when working with patients, drafting
      recovery criteria, and interpreting treatment outcomes.

PMID- 29182008
TI  - Aberrant expression of PlncRNA-1 and TUG1: potential biomarkers for gastric
      cancer diagnosis and clinically monitoring cancer progression.
AB  - AIM: To evaluate PlncRNA-1, TUG1 and FAM83H-AS1 gene expression and their
      possible role as a biomarker in gastric cancer (GC) progression. PATIENTS &
      METHODS: Long noncoding RNA expressions and clinicopathological characteristics
      were assessed in 70 paired GC tissues. Furthermore, corresponding data from 318
      GC patients were downloaded from The Cancer Genome Atlas database. RESULTS:
      Expression of PlncRNA-1 and TUG1 were significantly upregulated in GC tumoral
      tissues, and significantly correlated with clinicopathological characters.
      However, FAM83H-AS1 showed no consistently differential expression. The
      expression of these three long noncoding RNAs was significantly higher in The
      Cancer Genome Atlas tumoral tissues. CONCLUSION: In conclusion, PlncRNA-1 and
      TUG1 genes may play a critical role in GC progression and may serve as potential
      diagnostic biomarkers in GC patients.

PMID- 29182009
TI  - Systematic Changes in Preference for Schedule-Thinning Arrangements as a Function
      of Relative Reinforcement Density.
AB  - We treated destructive behavior maintained by both social-positive (i.e., access
      to tangibles) and social-negative (i.e., escape from demands) reinforcement in an
      individual diagnosed with autism spectrum disorder using functional communication
      training (FCT). We then thinned the schedule of reinforcement for the tangible
      function using a multiple schedule (mult FCT) and later thinned the availability
      of escape using a chained schedule (chain FCT). Both treatments proved effective
      at maintaining functional communicative responses while decreasing destructive
      behavior to near-zero levels. In addition, treatment effects maintained when we
      rapidly thinned mult FCT to the terminal schedule. Throughout chain-FCT schedule
      thinning, we assessed client preference for each schedule-thinning arrangement
      (mult FCT or chain FCT) using a concurrent-chains procedure. Client preference
      reliably shifted from chain FCT to mult FCT as the response requirement increased
      and the proportion of session spent in reinforcement began to favor mult FCT. We
      discuss the clinical implications of these findings.

PMID- 29182010
TI  - New antioxidant treatment with yerba mate ( Ilex paraguariensis) infusion for
      fresh-cut apples: Modeling, optimization, and acceptability.
AB  - Enzymatic browning affects the sensory and nutritional quality of fresh-cut
      apples and limits their shelf-life. Yerba mate ( Ilex paraguariensis), a plant
      widely consumed in South America as an infusion, could potentially be used in
      minimally processed fruits and vegetables as a natural additive to prevent
      browning, due to its high content of phenolic compounds with antioxidant
      capacity. The effects of the concentrations of ascorbic acid, citric acid, and
      yerba mate in an aqueous dipping solution on the instrumental color parameters,
      antioxidant capacity, and sensory quality of "Granny Smith" fresh-cut apples were
      modeled and the solution was optimized to obtain treated apples with maximum
      antioxidant capacity and minimum browning, without affecting the natural flavor
      of the fruits. The optimal composition obtained (1.2% yerba mate  + 0.9% citric
      acid + 1.0% ascorbic acid) increased the antioxidant capacity of the apples by
      36%. The sensory acceptability test carried out on the "Granny Smith" fresh-cut
      apples treated with the optimal dipping solution showed that more than 78% of the
      surveyed consumers liked the color, flavor, and texture of the apples.

PMID- 29182011
TI  - Mobile Technology-Based Real-Time Teleotolaryngology Care Facilitated by a
      Nonotolaryngologist Physician in an Adult Population.
AB  - OBJECTIVES: Telehealth can improve access to specialist care. Very few reports of
      the use of smartphones for teleotolaryngology exist. The objective of this study
      is to evaluate the use of mobile teleotolaryngology facilitated by a
      nonotolaryngologist physician. METHODS: A prospective study in adult patients
      attending a general otolaryngology outpatient clinic. The telehealth encounter
      with a remote otolaryngologist was facilitated by a final-year medical student
      simulating a general physician prior to the scheduled visit. The patient and the
      remote otolaryngologist rated their satisfaction with the encounter. The remote
      otolaryngologist formulated a diagnosis and rated the level of certainty of this
      diagnosis. Diagnoses from the telehealth encounter and the face-to-face encounter
      were compared. RESULTS: Forty-eight patients with an average age of 42.5 years
      participated in this study. In 79.2% of the consultations, there was concordance
      between the diagnoses. The average patient and remote otolaryngologist
      satisfaction with the encounter was 9.5 +/- 0.9 and 8.7 +/- 1.3, respectively.
      Twenty-four of the 48 visits (50%) were defined as unnecessary. In the otology
      group, concordance rates and rates of preventable visits were highest.
      CONCLUSIONS: Synchronous telehealth consultations, facilitated by a general
      physician, can be an alternative to visiting a general otolaryngology clinic,
      especially for otologic patients.

PMID- 29182012
TI  - Validating Online Measures of Cognitive Ability in Genes for Good, a Genetic
      Study of Health and Behavior.
AB  - Genetic association studies routinely require many thousands of participants to
      achieve sufficient power, yet accumulation of large well-assessed samples is
      costly. We describe here an effort to efficiently measure cognitive ability and
      personality in an online genetic study, Genes for Good. We report on the first
      21,550 participants with relevant phenotypic data, 7,458 of whom have been
      genotyped genome-wide. Measures of crystallized and fluid intelligence reflected
      a two-dimensional latent ability space, with items demonstrating adequate item
      level characteristics. The Big Five Inventory questionnaire revealed the expected
      five-factor model of personality. Cognitive measures predicted educational
      attainment over and above personality characteristics, as expected. We found that
      a genome-wide polygenic score of educational attainment predicted educational
      level, accounting for 4%, 4%, and 2.7% of the variance in educational attainment,
      verbal reasoning, and spatial reasoning, respectively. In summary, the online
      cognitive measures in Genes for Good appear to perform adequately and demonstrate
      expected associations with personality, education, and an education-based
      polygenic score. Results indicate that online cognitive assessment is one avenue
      to accumulate large samples of individuals for genetic research of cognitive
      ability.

PMID- 29182013
TI  - Friend or foe? Mitochondria as a pharmacological target in cancer treatment.
AB  - Mitochondria have acquired numerous functions over the course of evolution, such
      as those involved in controlling energy production, cellular metabolism, cell
      survival, apoptosis and autophagy within host cells. Tumor cells can develop
      defects in mitochondrial function, presenting a potential strategy for designing
      selective anticancer therapies. Therefore, cancer has been the main focus of
      recent research to uncover possible mitochondrial targets for therapeutic
      benefit. This comprehensive review covers not only the recent discoveries of the
      roles of mitochondria in cancer development, progression and therapeutic
      implications but also the findings regarding emerging mitochondrial therapeutic
      targets and mitochondria-targeted agents. Current challenges and future
      directions for developments and applications of mitochondrial-targeted
      therapeutics are also discussed.

PMID- 29182014
TI  - Emodin attenuates cell injury and inflammation in pancreatic acinar AR42J cells.
AB  - The study was intended to investigate the protective effects of emodin against
      cell injury and inflammation in AR42J cells. We determined trypsin and lipase
      activity, intracellular ROS and MMP using specific assay kits. The related
      protein expression and TNF-alpha and IL-6 in the medium were assayed by Western
      blot and ELISA kits. Results showed that emodin could protect AR42J cells against
      cell injury caused by cerulein and lipopolysaccharide which were possibly
      associated with inhibition of mitochondrial damage, ROS production, and then
      significantly inhibited ROS-mediated pathway, and ameliorated pancreatic cells
      injury by depleting the levels of inflammatory cytokines.

PMID- 29182015
TI  - Toward the clinical use of circulating biomarkers predictive of bone union.
AB  - Current methods for diagnosis of bone healing after treatment of trauma injuries
      rely on clinical findings and the use of imaging methodologies that provide
      conclusive results but only at mid/long-term post-intervention. In this
      Perspective we present and discuss incipient evidence on biomarkers that may
      serve for monitoring the progression of bone healing as well as predicting
      eventual nonunion outcomes.

PMID- 29182017
TI  - Compressive Detection of Highly Overlapped Spectra Using Walsh-Hadamard-Based
      Filter Functions.
AB  - In the chemometric context in which spectral loadings of the analytes are already
      known, spectral filter functions may be constructed which allow the scores of
      mixtures of analytes to be determined in on-the-fly fashion directly, by applying
      a compressive detection strategy. Rather than collecting the entire spectrum over
      the relevant region for the mixture, a filter function may be applied within the
      spectrometer itself so that only the scores are recorded. Consequently,
      compressive detection shrinks data sets tremendously. The Walsh functions, the
      binary basis used in Walsh-Hadamard transform spectroscopy, form a complete
      orthonormal set well suited to compressive detection. A method for constructing
      filter functions using binary fourfold linear combinations of Walsh functions is
      detailed using mathematics borrowed from genetic algorithm work, as a means of
      optimizing said functions for a specific set of analytes. These filter functions
      can be constructed to automatically strip the baseline from analysis. Monte Carlo
      simulations were performed with a mixture of four highly overlapped Raman
      loadings and with ten excitation-emission matrix loadings; both sets showed a
      very high degree of spectral overlap. Reasonable estimates of the true scores
      were obtained in both simulations using noisy data sets, proving the linearity of
      the method.

PMID- 29182016
TI  - Improved antifouling properties of photobioreactors by surface grafted
      sulfobetaine polymers.
AB  - To improve the antifouling (AF) properties of photobioreactors (PBR) for
      microalgal cultivation, using trihydroxymethyl aminomethane (tris) as the linking
      agent, a series of polyethylene (PE) films grafted with sulfobetaine (PE-SBMA)
      with grafting density ranging from 23.11 to 112 MUg cm-2 were prepared through
      surface-initiated atom transfer radical polymerization (SI-ATRP). It was found
      that the contact angle of PE-SBMA films decreased with the increase in the
      grafting density. When the grafting density was 101.33 MUg cm-2, it reached 67.27
      degrees . Compared with the PE film, the adsorption of protein on the PE-SBMA
      film decreased by 79.84% and the total weight of solid and absorbed microalgae
      decreased by 54.58 and 81.69%, respectively. Moreover, the transmittance of PE
      SBMA film recovered to 86.03% of the initial value after cleaning, while that of
      the PE film recovered to only 47.27%. The results demonstrate that the AF
      properties of PE films were greatly improved on polySBMA-grafted surfaces.

PMID- 29182018
TI  - Structure-activity relationships of hydroxamate-based histone deacetylase-8
      inhibitors: reality behind anticancer drug discovery.
AB  - The pan-histone deacetylase (HDAC) inhibitors comprise a fish-like structural
      orientation where hydrophobic aryl- and zinc-binding groups act as head and tail,
      respectively of a fish. The linker moiety correlates the body of the fish linking
      head and tail groups. Despite these pan-HDAC inhibitors, selective HDAC-8
      inhibitors are still in demand as a safe remedy. HDAC-8 is involved in invasion
      and metastasis in cancer. This review deals with the rationale behind HDAC-8
      inhibitory activity and selectivity along with detailed structure-activity
      relationships of diverse hydroxamate-based HDAC-8 inhibitors. HDAC-8 inhibitory
      potency may be increased by modifying the fish-like pharmacophoric features of
      such type of pan-HDAC inhibitors. This review may provide a preliminary basis to
      design and optimize new lead molecules with higher HDAC-8 inhibitory activity.
      This work may surely enlighten in providing useful information in the field of
      target-specific anticancer therapy.

PMID- 29182019
TI  - Pain and Function Following Revision Cubital Tunnel Surgery.
AB  - BACKGROUND: The purpose of this study was to determine pain and functional
      outcomes following revision cubital tunnel surgery and to identify predictors of
      poor postoperative outcome. METHODS: A retrospective cohort study was conducted
      of all patients undergoing revision cubital tunnel surgery over a 5-year period
      at a high-volume peripheral nerve center. Intraoperative findings, demographic
      and injury factors, and outcomes were reviewed. Average pain, worst pain, and
      impact of pain on self-perceived quality of life were each measured using a 10-cm
      visual analog scale (VAS). Function was evaluated using pinch and grip strength,
      as well as the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire.
      Differences in preoperative and postoperative pain, strength, and DASH were
      analyzed using nonparametric tests. Predictors of postoperative average pain were
      evaluated using odds ratios and linear regression analyses. RESULTS: The final
      cohort consisted of 50 patients (mean age: 46.3 +/- 12.5 years; 29 [68%] male)
      undergoing 52 revision ulnar nerve transpositions (UNTs). Pain VAS scores
      decreased significantly following revision UNT. Strength and DASH scores
      demonstrated nonsignificant improvements postoperatively. Worse preoperative pain
      and greater than 1 prior cubital tunnel procedure were significant predictors of
      worse postoperative average pain VAS scores. CONCLUSIONS: Patients can and do
      improve following revision cubital tunnel surgery, particularly as it relates to
      pain. Intraoperative findings during the revision procedure suggest that
      adherence to specific principles in the primary operation is key to prevention of
      secondary cubital tunnel syndrome.

PMID- 29182020
TI  - New cycloartanes and new iridoids from Dolichandrone spathacea collected in the
      mangrove forest of Soc Trang province, Vietnam.
AB  - Two new cycloartanes, named dolichandrone A (1) and dolichandrone B (2), as well
      as two new iridoids, named [6-O-[(E)-4-methoxycinnamoyl]-1beta-hydroxy
      dihydrocatalpolgenin (3) and 6-O-[(E)-4-methoxycinnamoyl]-1alpha-hydroxy
      dihydrocatalpolgenin (4), together with four known iridoids (5-8), were isolated
      from the leaves and barks of Dolichandrone spathacea. Their structures were
      elucidated by means of extensive analysis of their HRESIMS, 1D and 2D NMR
      spectroscopic data. All of these compounds have been isolated for the first time
      from this plant. Compounds 1, 2, 5, and 7 were evaluated for their cytotoxic
      activity in vitro against four human cancer cell lines KB, Lu, HepG2, and MCF7.
      The results showed that only compound 2 exhibited a good cytotoxicity against KB
      cell line with IC50 of 18.77 MUM.

PMID- 29182021
TI  - Injuries Depicted in Sport-Related Films.
AB  - The perception that children and adolescents have of injuries may be influenced
      by their depiction in sport-related films. The objective of this study was to
      determine the depiction of injuries in a select number of sport-related films.
      Forty-four films were analyzed. Injury category, on-the-field management, and
      long-term management were determined for each injury. Major injuries were defined
      as injuries requiring prompt intervention and immediate discontinuation of sport
      participation. A total of 49 injuries were depicted, categorized as fracture (n =
      11), contusion (n = 10), brain concussion (n = 8), muscle cramps (n = 5),
      laceration/abrasion (n = 4), ligamentous knee injury (n = 4), shoulder
      dislocation (n = 2), rotator cuff injury (n = 2), ankle sprain (n = 2), and
      unspecified injury (n = 1). Of the 38 (78%) injuries considered major, immediate
      return to the game was the disposition for 13 injuries (34%). Pediatric health
      care providers, coaching staff, and parents should stress the importance of
      injury recognition/disclosure and realistic expectations for rehabilitation to
      pediatric athletes.

PMID- 29182022
TI  - Persistent Perianal Rash in a Young Boy.

PMID- 29182023
TI  - PDGFRbeta-specific affibody-directed delivery of a photosensitizer, IR700, is
      efficient for vascular-targeted photodynamic therapy of colorectal cancer.
AB  - Vascular-targeted photodynamic therapy (PDT) is an important strategy for cancer
      therapy. Conventional vascular-targeted PDT has been achieved by passive
      photosensitizer (PS) delivery, which involves a high risk of adverse effects.
      Active PS delivery is urgently required for vascular-targeted PDT. Although
      endothelial cells and pericytes are major cellular components of tumor blood
      vessels, little attention has been paid to pericyte-targeted PDT for cancer
      therapy. PDGFRbeta is abundantly expressed in the pericytes of various tumors. In
      this experiment, a dimeric ZPDGFRbeta affibody with a 0.9 nM affinity for
      PDGFRbeta was produced. The ZPDGFRbeta affibody showed PDGFRbeta-dependent
      pericyte binding. Intravenously injected ZPDGFRbeta affibody was predominantly
      distributed on pericytes and thus accumulated in LS174T tumor grafts. The
      conjugate of the ZPDGFRbeta affibody and IR700 dye, i.e. ZIR700, bound to
      PDGFRbeta+ pericytes but not to PDGFRbeta- LS174T tumor cells. Accordingly,
      ZIR700-mediated PDT in vitro induced the death of pericytes but not of LS174T
      tumor cells. In mice bearing LS174T tumor grafts, ZIR700-mediated PDT damaged
      tumor blood vessels, thus inducing tumor destruction by intensifying tissue
      hypoxia. The average mass of tumor grafts administered with ZIR700-mediated PDT
      was approximately 20-30% of that of the control, indicating that pericyte
      targeted PDT is efficient for cancer therapy. In addition, ZIR700-mediated PDT
      increased the tumor uptake of TNF-related apoptosis-inducing ligand (TRAIL)
      injected post-illumination. Consequently, combination therapy of ZIR700-mediated
      PDT and TRAIL showed greater tumor suppression than ZIR700-mediated PDT- or TRAIL
      based monotherapy. These results demonstrated that active vascular-targeted PDT
      could be achieved by using ZPDGFRbeta affibody-directed delivery of PS.

PMID- 29182024
TI  - First nationwide survey on systemic wild-type ATTR amyloidosis in Japan.
AB  - OBJECTIVE: A nationwide survey on systemic wild-type ATTR (ATTRwt) amyloidosis
      was conducted to elucidate the frequency, clinical picture and possible
      diagnostic issues of ATTRwt amyloidosis in Japan. METHODS: A questionnaire was
      sent to 4629 clinical departments across Japan. A total of 2341 (50.6%) responses
      were returned completed for further analysis. RESULTS: Fifty-one patients with
      ATTRwt amyloidosis (82% male) were identified between January 2012 and December
      2014. The study subjects were identified in 11 departments at 10 institutes. The
      mean age of onset and diagnosis were 71.6 and 73.6 years, respectively. The main
      clinical findings were cardiac failure (76%), cardiac conduction
      defects/arrhythmia (59%), renal dysfunction (49%), carpal tunnel syndrome (45%)
      and spinal canal stenosis (22%). CONCLUSIONS: ATTRwt amyloidosis is diagnosed in
      a limited number of institutes in Japan and is therefore considered to be
      underdiagnosed.

PMID- 29182025
TI  - VEGF-mediated tight junctions pathological fenestration enhances doxorubicin
      loaded glycolipid-like nanoparticles traversing BBB for glioblastoma-targeting
      therapy.
AB  - The existence of blood-brain barrier (BBB) greatly hindered the penetration and
      accumulation of chemotherapeutics into glioblastoma (GBM), accompany with poor
      therapeutic effects. The growth of GBM supervene the impairment of tight
      junctions (TJs); however, the pathogenesis of BBB breakdown in GBM is essentially
      poorly understood. This study found that vascular endothelial growth factor
      (VEGF) secreted by GBM cells plays an important role in increasing the
      permeability of BBB by disrupting endothelial tight junction proteins claudin-5
      and thus gave doxorubicin (DOX)-loaded glycolipid-like nanoparticles (Ap
      CSSA/DOX), an effective entrance to brain tumor region for GBM-targeting therapy.
      In addition, VEGF downregulates the expression of claudin-5 with a dose-dependent
      mode, and interfering with the VEGF/VEGFR pathway using its inhibitor axitinib
      could reduce the permeability of BBB and enhance the integrity of the barrier. Ap
      CSSA/DOX nanoparticles showed high affinity to expressed low-density lipoprotein
      receptor-related proteins 1 (LRP1) in both BBB and GBM. And BBB pathological
      fenestration in GBM further exposed more LRP1 binding sites for Ap-CSSA/DOX
      nanoparticles targeting to brain tumor, resulting in a higher transmembrane
      transport ratio in vitro and a stronger brain tumor biodistribution in vivo, and
      finally realizing a considerable antitumor effect. Overall, taking advantage of
      BBB pathological features to design an appropriate nanodrug delivery system
      (NDDS) might provide new insights into other central nervous system (CNS)
      diseases treatment.

PMID- 29182026
TI  - Extensor Carpi Ulnaris Tenodesis Versus No Stabilization After Wide Resection of
      Distal Ulna Giant Cell Tumors.
AB  - BACKGROUND: The necessity of stabilizing the residual ulnar stump after distal
      ulna tumor resection remains controversial. The authors retrospectively compared
      the outcome of patients who underwent wide resection of distal ulna giant cell
      tumors (GCTs) and reconstruction with tenodesis of the extensor carpi ulnaris
      (ECU) or without reconstruction. METHODS: Between 2007 and 2015, 9 patients (6
      females, 3 males; mean age, 36.8 years; range, 24-65 years) who underwent distal
      ulna resection for GCT of bone were retrospectively reviewed. The mean resection
      length was 8.1 cm. Five patients had no reconstruction, whereas 4 patients had
      stabilization of the ulnar stump using ECU tenodesis. With a mean follow-up of
      3.6 years (2-9 years), the functional outcome using the quick Disability of Arm,
      Shoulder and Hand (DASH) score; Musculoskeletal Tumor Society score and grip
      strength; as well as the oncological outcome were evaluated. RESULTS:
      Musculoskeletal Tumor Society functional scores were more than 24 in 7 patients
      and 20 to 24 in 2 patients (mean, 27.6 or 92%). Quick DASH scores ranged from 0
      to 27.3 (mean, 11.1). In both groups, similar scores were observed ( P > .5). No
      patient had instability or pain related to the stump. There was no ulnar
      translation or subluxation of the radiocarpal joint. Grip strength in the
      operated hand, controlled for handedness, was 11% less than in the contralateral
      hand, although there was no difference between groups ( P > .4). All patients
      were disease-free at the latest follow-up. CONCLUSIONS: The distal ulna may be
      widely resected with or without stabilization of the residual ulnar stump,
      yielding satisfactory local disease control and functional outcome.

PMID- 29182027
TI  - How development of blood biomarkers could benefit prehospital management of acute
      stroke.

PMID- 29182028
TI  - Altered expression of lysophosphatidic acid receptors, in association with the
      synthesis of estrogens and androgens in type 1 endometrial cancer biology.
AB  - To establish association between two main lysophosphatidic acid (LPA) receptors
      (LPAR2 and LPAR1) with the synthesis of estrogens and androgens in type-1
      endometrial carcinoma (EC), we evaluated correlation of LPARs expression with
      expression of steroid 5 alpha-reductase 2 - aromatase (SRD5A2), or cytochrome
      P450 family 19 subfamily A member 1-5alpha-reductase (CYP19A1) in EC. Moreover,
      we aimed to investigate SRD5A2 and CYP19A1 expression in type 1 endometrial
      cancer and normal endometrium with its correlation to selected
      clinicopathological features. The studied cancerous samples showed higher CYP19A1
      and SRD5A2 expression comparing to normal endometria. We also documented positive
      correlations between LPAR1 and LPAR2 with responsible for proliferation SRD5A2 in
      EC tissue which suggests that intratumoral estrogen metabolism and synthesis are
      pivotal in endometrial carcinoma progression, with the involvement of LPA in this
      process. However, positive correlation between CYP19A1 and LPAR1 accounts for
      supporting role of LPA acting via LPAR1 in intratumoral DHT concentration and the
      ethiology of endometrial cancer progression. Also, owing to the highest
      expression of LPARs, CYP19A1 and SRD5A2 as well as their association with depth
      of myoinvasion and FIGO stage LPAR2 and LPAR1 seem to be the efficient candidate
      prognostic markers in the individual, targeted therapies for EC.

PMID- 29182029
TI  - Strategies to keep working among workers with common mental disorders - a
      grounded theory study.
AB  - PURPOSE: Most people with common mental disorders (CMDs) are employed and
      working, but few studies have looked into how they manage their jobs while ill.
      This study explores workers' experiences of strategies to keep working while
      suffering from CMDs. METHODS: In this grounded theory study, we interviewed 19
      women and eight men with depression or anxiety disorders. They were 19-65 years
      old and had different occupations. Constant comparison method was used in the
      analysis. RESULTS: We identified a core pattern in the depressed and anxious
      workers' attempts to sustain their capacities, defined as Managing work space.
      The core pattern comprised four categories describing different cognitive,
      behavioral, and social strategies. The categories relate to a process of
      sustainability. Two categories reflected more reactive and temporary strategies,
      occurring mainly in the onset phase of illness: Forcing the work role and Warding
      off work strain. The third category, Recuperating from work, reflected strategies
      during both onset and recovery phases. The fourth category, Reflexive adaptation,
      was present mainly in the recovery phase and involved reflective strategies
      interpreted as more sustainable over time. CONCLUSIONS: The results can deepen
      understanding among rehabilitation professionals about different work-related
      strategies in depressed and anxious workers. Increased awareness of the meaning
      and characteristics of strategies can inform a person-oriented approach in
      rehabilitation. The knowledge can be used in clinical encounters to reflect
      together with the patient, exploring present options and introducing
      modifications to their particular work and life context. Implications for
      rehabilitation Self-managed work functioning in common mental disorders involves
      diverse strategies. Strategies interpreted as sustainable over time, seem to be
      reflective in the sense that the worker consciously applies and adapts the
      strategies. However, at the onset of illness, such reflection is difficult to
      develop as the worker might not want to realize their reduced functioning.
      Rehabilitation professionals' awareness of different strategies can facilitate a
      person-centered approach and understanding of the vocational rehabilitation
      process.

PMID- 29182030
TI  - Biomarkers of ocular surface disease using impression cytology.
AB  - Impression cytology (IC) is a technique which permits the retrieval of the
      outermost layer of ocular surface cells via the use of various types of filters.
      It is a minimally invasive method of evaluating human conjunctival epithelial
      cell morphology in the diagnosis of dry eye disease, a common and distressing
      disorder associated with ageing, contact lens wear, autoimmune disorders and
      refractive (LASIK) surgery. IC may also be utilized in the diagnosis of other
      ocular diseases, such as keratoconus and thyroid orbitopathy. More recently, IC
      has been utilized for the subsequent investigation of gene and protein expression
      of conjunctival cells in order to identify novel diagnostic biomarkers and to
      further our understanding of the mechanisms underlying ocular surface disease.
      This review will therefore examine the literature concerning the role of IC in
      identifying cellular markers of eye disease, systemic diseases with ocular
      involvement and potential novel therapeutic targets.

PMID- 29182031
TI  - Recent developments in d-alpha-tocopheryl polyethylene glycol-succinate-based
      nanomedicine for cancer therapy.
AB  - Cancer remains an obstacle to be surmounted by humans. As an FDA-approved
      biocompatible drug excipient, d-alpha-tocopheryl polyethylene glycol succinate
      (TPGS) has been widely applied in drug delivery system (DDS). Along with in-depth
      analyses of TPGS-based DDS, increasingly attractive results have revealed that
      TPGS is able to act not only as a simple drug carrier but also as an assistant
      molecule with various bio-functions to improve anticancer efficacy. In this
      review, recent advances in TPGS-based DDS are summarized. TPGS can inhibit P
      glycoprotein, enhance drug absorption, induce mitochondrial-associated apoptosis
      or other apoptotic pathways, promote drug penetration and tumor accumulation, and
      even inhibit tumor metastasis. As a result, many formulations, by using original
      TPGS, TPGS-drug conjugates or TPGS copolymers, were prepared, and as expected, an
      enhanced therapeutic effect was achieved in different tumor models, especially in
      multidrug resistant and metastatic tumors. Although the mechanisms by which TPGS
      participates in such functions are not yet very clear, considering its
      effectiveness in tumor treatment, TPGS-based DDS appears to be one of the best
      candidates for future clinical applications.

PMID- 29182032
TI  - Squamous Cell Carcinoma of the Bulbar Urethra Accompanied by Lichen Sclerosus: A
      Case Report.
AB  - Squamous cell carcinoma (SCC) of the bulbar urethra accompanied by lichen
      sclerosus (LS) is rarely reported. This study reports the case of a 56-year-old
      man with urethral squamous cell carcinoma (USCC) accompanied by a long history of
      genital LS. The man presented with a painful perineal mass and had a long-term
      history of urethral strictures and urethral dilatation. The patient developed a
      periurethral abscess that expanded to the perineum and formed an
      urethrocutaneousperineal fistula. An organ-sparing perineal resection and
      fistulectomy was performed according to the patient's wishes. During the
      operation, residue-like pus mixed with necrotic tissues drained out. A section of
      the prepuce and the necrotic tissues were sent for histological analysis.
      Hematoxylin and eosin (HE) staining of the excised prepuce revealed classical LS.
      HE and immunohistochemical (IHC) staining of the necrotic tissues showed well
      differentiated USCC. IHC staining showed the USCC to be positive for P53 and Ki
      67 and negative for P16, suggesting the USCC was probably associated with LS. The
      patient received high-dose chemotherapy and radiation therapy and died 10 months
      after surgery.

PMID- 29182033
TI  - Influence of physical activity on the health-related quality of life of young
      adults with and without autism spectrum disorder.
AB  - BACKGROUND: Health-related quality of life constructs has been used to understand
      the multiple dimensions (i.e., physical health, psychological, environment and
      social relationships) that affect a person's health status. In order to improve
      health-related quality of life for young adults, it is important to understand
      the factors that influence each dimension. The purpose of this paper was to
      examine the influence of the presence of autism spectrum disorder and physical
      activity on the multiple domains of health-related quality of life for young
      adults. METHODS: Three-hundred and twenty participants, including young adults
      with ASD, completed a questionnaire about their physical activity and health
      related quality of life. RESULTS: Five multiple regressions revealed that the
      presence of autism spectrum disorder significantly predicted overall health
      related quality of life, the physical health domain, psychological domain, and
      the environment domain. Additionally, physical activity significantly predicted
      each domain and overall health-related quality of life regardless of the presence
      of autism spectrum disorder. CONCLUSION: Practitioners should recognize the
      limitations that individuals with autism spectrum disorder may experience
      regarding their health-related quality of life, and utilize physical activity as
      a tool for improving health-related quality of life. Implications for
      Rehabilitation In order to address an individual's overall health, practitioners
      must consider multiple dimensions of health-related quality of life. Autism
      spectrum disorders influence how people perceive multiple dimensions of their
      health. Physical activity is a tool for improving perceptions of the multiple
      dimensions of health for individuals with and without autism spectrum disorders.

PMID- 29182035
TI  - Oral Health of Children With Attention Deficit Hyperactivity Disorder: Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: This systematic review investigated the oral health of children with
      ADHD. METHOD: A structured search strategy was performed on five electronic
      databases: SCOPUS, Web of Science, COCHRANE, PubMed, and PsychInfo. Studies were
      included in the review if they reported clinical oral health outcomes on a
      population diagnosed with ADHD under the age of 18 years old. Qualitative and
      quantitative analysis was performed on pooled prevalence and mean/median values
      for caries, trauma, periodontal problems, and tooth wear. RESULTS: Twenty-seven
      effective articles were reviewed by two calibrated assessors. Meta-analysis of
      the results found higher mean number of decayed surfaces, plaque index, and
      trauma prevalence among children with ADHD. CONCLUSION: Children with ADHD show
      increased risk for caries and traumatic dental injuries, and may have poorer oral
      hygiene compared with children without ADHD. More awareness among clinicians
      would promote better caries- and trauma-preventive advice and management.

PMID- 29182036
TI  - The Stanmore Nursing Assessment of Psychological Status (SNAPS): not just for
      spinal cord injury rehabilitation?
AB  - Spinal cord injury is an uncommon condition, potentially causing a wide range of
      consequences and requiring specialist rehabilitation to optimize health, activity
      and participation. Early psychological response to injury and relations with
      staff, as well as family, may set the foundations for long-term emotional
      adjustment, healthcare utilization and quality of life. The Stanmore Nursing
      Assessment of Psychological Status has been developed at the London Spinal Cord
      Injury Centre to empower nurses to adopt a consistently empathic approach to
      patient care, as part of a comprehensive range of rehabilitation team skills. Its
      use in other spinal cord injury centers and a broader range of clinical
      environments (hospital and community) should therefore be considered.

PMID- 29182034
TI  - Molecular Imaging and Radionuclide Therapy of Melanoma Targeting the Melanocortin
      1 Receptor.
AB  - Melanoma is a deadly disease at late metastatic stage, and early diagnosis and
      accurate staging remain the key aspects for managing melanoma. The melanocortin 1
      receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its
      endogenous ligand, the alpha-melanocyte-stimulating hormone (alphaMSH), has been
      extensively studied for the development of MC1 R-targeted molecular imaging and
      therapy of melanoma. Natural alphaMSH is not well suited for this purpose due to
      low stability in vivo. Unnatural amino acid substitutions substantially
      stabilized the peptide, while cyclization via lactam bridge and metal
      coordination further improved binding affinity and stability. In this study, we
      summarized the development and the in vitro and in vivo characteristics of the
      radiolabeled alphaMSH analogues, including 99mTc-, 111In-, 67 Ga-, or 125I
      labeled alphaMSH analogues for imaging with single-photon emission computed
      tomography; 68Ga-, 64Cu-, or 18F-labeled alphaMSH analogues for imaging with
      positron emission tomography; and 188Re-, 177Lu-, 90Y-, or 212Pb-labeled alphaMSH
      analogues for radionuclide therapy. These radiolabeled alphaMSH analogues showed
      promising results with high tumor uptake and rapid normal tissue activity
      clearance in the preclinical model of B16F1 and B16F10 mouse melanomas. These
      results highlight the potential of using radiolabeled alphaMSH analogues in
      clinical applications for molecular imaging and radionuclide therapy of melanoma.

PMID- 29182037
TI  - DRD4 exon 3 genotype and ADHD: Randomised pharmacodynamic investigation of
      treatment response to methylphenidate.
AB  - OBJECTIVES: Dopamine plays an important role in modulating attention and motor
      behaviours, dimensions altered in attention deficit/hyperactivity disorder
      (ADHD). Numerous association studies have linked dopamine receptor 4 (DRD4) to
      increased risk of ADHD. This study investigated the effect of DRD4 exon 3
      polymorphism on child behaviours in response to treatment with methylphenidate.
      METHODS: A total of 374 children diagnosed with ADHD (ages 6-12 years) were
      evaluated under three experimental conditions: baseline, placebo and MPH (0.5
      mg/kg/day). This was a 2-week prospective within-subject, placebo-controlled,
      crossover trial. The Conners' Global Index for parents and for teachers was used
      to evaluate the behaviours of the children. One-way repeated measures analysis of
      variance was used to test the effect of the interaction between DRD4 genotype and
      experimental conditions. RESULTS: A significant interaction between DRD4 genotype
      and treatment was detected when the child's behaviour was evaluated by the
      parents (P = 0.035, effect size of 0.014), driven by a better treatment response
      in children homozygous for long 7-repeat allele. CONCLUSIONS: According to the
      parent assessment, children homozygous for the long 7-repeat allele were more
      responsive to experimental condition. This is the largest pharmacogenetic
      investigation of the effect of DRD4 exon 3 polymorphism in childhood ADHD. TRIAL
      REGISTRATION: clinicaltrials.gov, identifier NCT00483106.

PMID- 29182038
TI  - The U.S. Health Care Crisis Continues: A Data Snapshot.
AB  - Despite implementation of the Affordable Care Act in 2014, the U.S. health care
      crisis continues. While coverage has been expanded, 28 million people remain
      uninsured, and tens of millions who have coverage are unable to afford care
      because of high cost-sharing requirements. Moreover, many with coverage have a
      sharply restricted choice of physicians and hospitals, and the corporate takeover
      of medical care in the United States is proceeding rapidly. This article provides
      a brief precis of recent data on U.S. health policy.

PMID- 29182040
TI  - Life Experience of Bereaved Parents After the 2014 Sewol Ferry Disaster in South
      Korea.
AB  - The aim of this study was to identify the outcomes of parental bereavement and
      the changes in life experience that follow the traumatic death of a teenage
      child. The results of the study are aimed to assist counselors and educators who
      work with themes of grief and loss. From 17 in-depth interviews from parents
      bereaved by the Sewol ferry disaster of 2014 in South Korea, three main
      categories were found to capture the reality for parents after the sudden and
      traumatic death of a teenage child: (a) personal changes, (b) changes in close
      relationships, and (c) changes in social life. Recommendations for future
      research and potential implications were discussed.

PMID- 29182039
TI  - Improvement of blood lipid profiles by Goishi tea polyphenols in a randomised,
      double-blind, placebo-controlled clinical study.
AB  - Dyslipidaemia is a risk factor for arteriosclerosis. Recent studies have shown
      that dyslipidaemia is effectively prevented by various polyphenols. In this
      clinical study (UMIN trial: 000024028), we evaluated the beneficial effects of
      polyphenols contained in Goishi tea on blood lipid profiles. Seventy-seven
      subjects with LDL cholesterol (CHO) ?120 mg/mL were randomly divided into two
      groups for 12 weeks of polyphenol intake as follows: the Goishi tea group for
      daily consumption of Goishi tea containing 122 mg of polyphenols and the placebo
      group for the corresponding consumption of a placebo drink containing 12.2 mg of
      polyphenols. Intake of Goishi tea polyphenols tended to increase HDL CHO and
      suppress the elevation of triglycerides. These effects were particularly notable
      among the subjects with a body mass index <25 kg/m2. These findings suggest that
      Goishi tea polyphenols may suppress arteriosclerosis and reduce cardiovascular
      event risk by improving blood lipid profiles and thereby preventing
      dyslipidaemia.

PMID- 29182042
TI  - Greater trochanteric pain syndrome and gluteus medius and minimus tendinosis:
      nonsurgical treatment.
AB  - Greater trochanteric pain syndrome (GTPS) affects 10-25% of people in developed
      countries. The underlying etiology for GTPS is most commonly the tendinosis or a
      tendon tear of the gluteus medius, minimus or both at the greater trochanter; the
      inflammation of the tendon is not a major feature. We critically evaluated
      conservative treatment, for which we reviewed 76 publications, grading them
      according to four levels of evidence. We identified a wide variety of
      conservative treatment options: home therapy (insoles, walking sticks/crutches,
      orthotic devices, stretching exercises and preventive measures); physiotherapy
      (massage and stretching exercises); infiltrations (corticosteroids and local
      anesthetics); image-guided infiltrations (fluoroscopy and ultrasound); shockwave
      therapy; platelet-rich plasma injection; and drug therapy. Severe complications
      associated with infiltrations are extremely rare, as are those associated with
      shockwave therapy. The most effective treatments were infiltrations with
      corticosteroids and shockwave therapy. We propose a graded treatment schedule for
      patients with GTPS.

PMID- 29182041
TI  - Characterization of Two Novel Deletions Involving the 5' Region of the beta
      Globin Gene.
AB  - We report two novel beta-thalassemia (beta-thal) deletions involving the 5'
      region of the beta-globin gene (HBB). The first deletion spans 538 bp and removes
      the beta-globin promoter, 5' untranslated region (5'UTR) and most of exon 1. This
      deletion was identified in a 3-year-old Vietnamese boy with non transfusion
      dependent Hb E (HBB: c.79G>A)/beta0-thal. The second deletion spans 1517 bp and
      removes the beta-globin gene promoter, 5'UTR, and exons 1 and 2. This deletion
      was identified in two unrelated adults of European descent who had beta-thal
      trait with unusually high Hb A2 levels. Deletions such as these are generally
      associated with higher levels of Hb A2 and Hb F than typical beta-thal alleles,
      which may ameliorate the severity of the disease.

PMID- 29182043
TI  - A cross-national exploration of societal-level factors associated with child
      physical abuse and neglect.
AB  - Children around the world experience violence at the hands of their caregivers at
      alarming rates. A recent review estimates that a minimum of 50% of children in
      Asia, Africa, and North America experienced severe physical violence by
      caregivers in the past year, with large variations between countries. Identifying
      modifiable country-level factors driving these geographic variations has great
      potential for achieving population-level reductions in rates of child
      maltreatment. This study builds on previous research by focusing on caregiver
      reported physical abuse and neglect victimisation, examining 22 societal factors
      representing 11 different constructs among 42 countries from 5 continents at
      different stages of development. Our findings suggest that gender inequity may be
      important for both child physical abuse and neglect. Indicators of literacy and
      development may also be important for child neglect. Given the limitations of the
      correlational findings and measurement issues, it is critical to continue to
      investigate societal-level factors of child maltreatment so that interventions
      and prevention efforts can incorporate strategies that have the greatest
      potential for population-level impact.

PMID- 29182044
TI  - Prerequisites and driving forces behind an extended working life among older
      workers.
AB  - BACKGROUND: Reforms are changing pension systems in many European countries, in
      order to both restrict early retirement and force people to extend their working
      life. From occupational therapy and occupational science perspectives, studies
      focusing on aspects of working life that motivate the older worker is urgent.
      AIM: The aim was to describe incentives behind an extended working life among
      people over age 65. METHOD: Focus group methodology was used, with participants
      ages 66-71, from varying work fields: construction and technical companies and
      the municipal elderly care sector. FINDINGS: Work was considered important and
      valuable to the degree of how challenging work was, the possibilities for
      inclusion in a team of colleagues and the chances for better personal finances.
      Amongst all, the participants expressed a feeling of a strengthened identity by
      being challenged and having the opportunity to manage working tasks. CONCLUSION:
      The finding showed the actual reasons behind an extended working life among older
      workers. However, a risk of rising social inequity may appear with increased
      working life if older people are forced to extend their working life due to a
      difficult financial situation as a pensioner. A variety of retirement options and
      initiatives in order to support older workers are justified.

PMID- 29182045
TI  - Corrigendum.

PMID- 29182046
TI  - Decolonizing Scoping Review Methodologies for Literature With, for, and by
      Indigenous Peoples and the African Diaspora: Dialoguing With the Tensions.
AB  - This article summarizes our deepened understanding of decolonizing research with,
      for, and by Indigenous peoples and peoples of African descent that emerged from
      conducting a scoping review of the methodological literature and reflecting on
      our review process. Although our review identified decolonizing methodologies as
      a promising approach, we questioned if our scoping review process engaged in
      decolonizing knowing. To unpack the epistemological tensions between decolonizing
      knowing and Western ways of doing scoping reviews, we engaged in individual and
      collective reflective processes- dialoguing with the tensions-moving from
      individual immersion in the literature to transformative dialogues among the
      team. In reflecting upon our tensions with the scoping review process, themes
      that emerged included (a) ontological/epistemological disjunctures, (b) tensions
      with concepts and language, and (c) relationships with the literature and beyond.
      This reflexive process provides valuable insight into ways in which review
      methods might be made a decolonizing research experience.

PMID- 29182047
TI  - The nuclear factor-kappa B pathway and response to treatment in breast cancer.
AB  - The nuclear factor-kappa B (NF-kappaB) pathway is known to contribute to critical
      signaling in cancer biology, including breast cancer, through promotion of
      proliferation, angiogenesis, metastasis, tumor progression, inflammation and cell
      survival. In this review, in vivo and in vitro studies of the NF-kappaB pathway
      in breast cancer are discussed, focusing on DNA damage and the epithelial
      mesenchymal transition associated with breast cancer stem cell properties. The
      relationships between NF-kappaB signaling and conventional cancer treatments in
      terms of response to chemo- and radiotherapy will also be discussed. Then
      contribution and involvement of immune system in the NF-kappaB pathway will be
      covered. Furthermore, the future perspective of NF-kappaB targeting as an
      innovative strategy to overcome refractory breast cancer, including recent
      updates on out-receptor activator of NF-kappaB (RANKing), will be covered.

PMID- 29182048
TI  - Cardiophrenic lymph node resection in advanced ovarian cancer: surgical outcomes,
      pre- and postoperative imaging.
AB  - OBJECTIVE: To evaluate the accuracy of preoperative imaging in the diagnosis of
      cardiophrenic lymph node (CPLN) metastases and to report perioperative outcomes
      after resection of CPLN at the time of cytoreductive surgery for advanced
      epithelial ovarian cancer (EOC). Furthermore, to assess clearance of CPLN by
      postoperative imaging. METHODS: All women with stage IIIC/IV EOC subjected to
      surgery at our institution from January 2014 to October 2016 were retrospectively
      identified from a database. Among these, women subjected to CPLN resection during
      surgery were identified. Pre- and postoperative computed tomography (CT) scans,
      pathology reports, surgical approach and outcomes were reviewed. RESULTS: One
      hundred and eighty women with stage IIIC/IV EOC subjected to surgery with
      curative intent were identified. Twenty-four (13%) of these women underwent CPLN
      resection. All had CT imaging suggestive of CPLN metastases. 20/24 (83%) had
      confirmed metastases upon final pathology. CPLN resection was associated with
      longer operation time, more often advanced upper abdominal surgery and more
      postoperative complications but there was no difference in days from surgery to
      initiation of chemotherapy. Postoperative CT was still indicative of CPLN
      metastases in 13/22 (59%) women despite resection with confirmative pathology.
      CONCLUSIONS: Resection of CPLN metastases is highly feasible without considerable
      added morbidity. Concern regarding surgical clearance is raised since
      postoperative imaging was indicative of metastases in the majority of women. The
      prognostic significance of stage IV disease based exclusively on CPLN metastases
      is unclear and any survival benefit from the procedure is yet to be determined.

PMID- 29182049
TI  - A qualitative study of two management models of community health centres in two
      Chinese megacities.
AB  - Two common public models of community health centres (CHCs) exist in China, i.e.
      the 'government-owned and government-managed' CHCs (G-CHCs) and the 'government
      owned and hospital-managed' CHCs (H-CHCs). Shanghai and Shenzhen are two Chinese
      megacities that lead the primary care development on the G-CHC and H-CHC models,
      respectively. Using a qualitative case study design, this study compares the
      management of the G-CHC model in Shanghai and H-CHC model in Shenzhen, through
      perspectives of a range of health providers. In each city, we randomly selected
      four CHCs and in total conducted 31 interviews with officers from the municipal
      health authorities, directors, GPs, nurses and public health doctors of the CHCs.
      When comparing with the H-CHC model in Shenzhen, the G-CHC model in Shanghai, a
      model with more simplified but accountable structure tended to present better
      management conditions, in terms of financial transparency, recruitment autonomy,
      community health workforce development (CHC staffing and family medicine
      training), funding and priority for public health. However, regardless of the
      models, staff retention remained a challenge. While our study tends to suggest
      that the G-CHC model in Shanghai presents better management conditions, future
      study can test whether and to what extent the model itself can lead to such
      differences.

PMID- 29182050
TI  - Erratum.
AB  - Moccia M, De Stefano N and Barkhof F. Imaging outcome measures for progressive
      multiple sclerosis trials. Mult Scler 2017; 23: 1614-1626. DOI:
      10.1177/1352458517729456. On pages 1614 and 1620 of this article, positron
      emission tomography was incorrectly spelled as position emission tomography. SAGE
      and the authors apologise for any confusion.

PMID- 29182051
TI  - What role does multiple sclerosis play in the development of untreatable painful
      conditions?
AB  - Clinical data outline the high incidence of pain syndromes in patients with
      multiple sclerosis, with a significant prevalence of craniofacial manifestations,
      including trigeminal neuralgia and migraine, which are very difficult to be
      managed pharmacologically. The common explanation of a localization of
      demyelinating plaques in areas devoted to pain modulation and integration as a
      trigger for pain development seems now partially unsatisfactory, since pain is
      often manifested well before the clinical signs of the pathology and its severity
      does not correlate with disease progression. This review focuses on additional
      mechanisms which could be at the basis of pain development in multiple sclerosis,
      whose identification will help identifying new targets to design more effective
      analgesic strategies.

PMID- 29182052
TI  - Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the
      three-class case-Application to the early diagnosis of Alzheimer disease.
AB  - Many medical diagnostic studies involve three ordinal diagnostic populations in
      which the diagnostic accuracy can be summarized by the volume or partial volume
      under the receiver operating characteristic surface for a diagnostic marker. When
      the diagnostic populations are clustered, e.g. by families, we propose to model
      the diagnostic marker by a general linear mixed model that takes into account of
      the correlation on the diagnostic marker from members of the same clusters. This
      model then facilitates the maximum likelihood estimation and statistical
      inferences of the diagnostic accuracy for the diagnostic marker. This approach
      naturally allows the incorporation of covariates as well as missing data when
      some clusters do not have subjects on all diagnostic groups in the estimation of,
      and the subsequent inferences on the diagnostic accuracy. We further study the
      performance of the proposed methods in a large simulation study with clustered
      data. Finally, we apply the proposed methodology to the data of several
      biomarkers collected by the Dominantly Inherited Alzheimer Network, an
      international family-clustered registry to study autosomal dominant Alzheimer
      disease which is a rare form of Alzheimer disease caused by mutations in any of
      the three genes including the amyloid precursor protein, presenilin 1 and
      presenilin 2. We estimate the accuracy of several cerebrospinal fluid and
      neuroimaging biomarkers in differentiating three diagnostic and genetic
      populations: normal non-mutation carriers, asymptomatic mutation carriers, and
      symptomatic mutation carriers.

PMID- 29182053
TI  - Identification of potential PKC inhibitors through pharmacophore designing, 3D
      QSAR and molecular dynamics simulations targeting Alzheimer's disease.
AB  - Protein kinases are ubiquitously expressed as Serine/Threonine kinases, and play
      a crucial role in cellular activities. Protein kinases have evolved through
      stringent regulation mechanisms. Protein kinases are also involved in tauopathy,
      thus are important targets for developing Anti-Alzheimer's disease compounds.
      Structures with an indole scaffold turned out to be potent new leads. With the
      aim of developing new inhibitors for human protein kinase C, here we report the
      generation of four point 3D geometric featured pharmacophore model. In order to
      identify novel and potent PKCtheta inhibitors, the pharmacophore model was
      screened against 80,000,00 compounds from various chemical databases such as.,
      ZINC, SPEC, ASINEX, which resulted in 127 compound hits, and were taken for
      molecular docking filters (HTVS, XP docking). After in-depth analysis of binding
      patterns, induced fit docking (flexible) was employed for six compounds along
      with the cocrystallized inhibitor. Molecular docking study reveals that compound
      6F found to be tight binder at the active site of PKCtheta as compared to the
      cocrystal and has occupancy of 90 percentile. MM-GBSA also confirmed the potency
      of the compound 6F as better than cocrystal. Molecular dynamics results suggest
      that compound 6F showed good binding stability of active sites residues similar
      to cocrystal 7G compound. Present study corroborates the pharmacophore-based
      virtual screening, and finds the compound 6F as a potent Inhibitor of PKC, having
      therapeutic potential for Alzheimer's disease. Worldwide, 46.8 million people are
      believed to be living with Alzheimer's disease. When elderly population increases
      rapidly and neurodegenerative burden also increases in parallel, we project the
      findings from this study will be useful for drug developing efforts targeting
      Alzheimer's disease.

PMID- 29182054
TI  - A Quantitative Method for the Evaluation of Spatial Resolution in Quality Control
      of B-mode Ultrasound Images.
AB  - The work describes a method to quantitatively evaluate spatial resolution in B
      mode quality control images as radial modulation transfer function (MTF). The
      method is easy to use in in-field quality assurance programs in clinical
      institutions, as it is fast and can be performed with the help of phantoms that
      are already used for routine quality control. It uses a round insert with
      different echogenic characteristics compared with the phantom background. The
      method was automated with a MATLAB(r) routine, which can be run in full automatic
      mode or with a grade of interaction by the user, as is sometimes necessary with
      low-quality images. Radial MTF was evaluated for several ultrasound (US) images
      produced with different clinical US scanners from various vendors and equipped
      with different types of transducers (linear, convex, sector, vector) working at
      various frequencies (from 2 to 14 MHz) and with different modalities. It was also
      evaluated on various computed tomography (CT) images including round inserts.
      This was done to compare these results with the MTF calculated from the same
      images using the well-known method from the point spread function (PSF) of a high
      contrast bead. Our radial MTF method, adapted to the specific characteristics of
      US images, was found to be reasonably robust and in line with other methods
      commonly used for USs (e.g., the pin method, which has repeatability issues) and
      in other fields, such as X-ray CT.

PMID- 29182055
TI  - Amyotrophic lateral sclerosis presenting as the temporomandibular disorder: A
      case report and literature review.
AB  - BACKGROUND: Spasticity and pain in the masticatory muscles or mouth opening
      limitation have been reported as early signs and symptoms of amyotrophic lateral
      sclerosis (ALS). These signs and symptoms are also frequently seen in, and thus
      mistaken for, temporomandibular disorders (TMD). CLINICAL PRESENTATION: The
      authors report a case of ALS initially presenting with signs and symptoms of TMD.
      The TMD was followed by dysarthria of insidious onset, leading to the diagnosis
      of ALS. This case highlights the importance of considering TMD as a potential
      early form of presentation of ALS, requiring multidisciplinary treatment,
      especially by dental professionals. CONCLUSION: A review of the literature was
      conducted to elucidate the oral and facial signs and symptoms of ALS and to
      identify ways of improving the quality of life of patients through a
      multidisciplinary approach.

PMID- 29182056
TI  - Lesion Segmentation in Automated 3D Breast Ultrasound: Volumetric Analysis.
AB  - Mammography is the gold standard screening technique in breast cancer, but it has
      some limitations for women with dense breasts. In such cases, sonography is
      usually recommended as an additional imaging technique. A traditional sonogram
      produces a two-dimensional (2D) visualization of the breast and is highly
      operator dependent. Automated breast ultrasound (ABUS) has also been proposed to
      produce a full 3D scan of the breast automatically with reduced operator
      dependency, facilitating double reading and comparison with past exams. When
      using ABUS, lesion segmentation and tracking changes over time are challenging
      tasks, as the three-dimensional (3D) nature of the images makes the analysis
      difficult and tedious for radiologists. The goal of this work is to develop a
      semi-automatic framework for breast lesion segmentation in ABUS volumes which is
      based on the Watershed algorithm. The effect of different de-noising methods on
      segmentation is studied showing a significant impact ([Formula: see text]) on the
      performance using a dataset of 28 temporal pairs resulting in a total of 56 ABUS
      volumes. The volumetric analysis is also used to evaluate the performance of the
      developed framework. A mean Dice Similarity Coefficient of [Formula: see text]
      with a mean False Positive ratio [Formula: see text] has been obtained. The
      Pearson correlation coefficient between the segmented volumes and the
      corresponding ground truth volumes is [Formula: see text] ([Formula: see text]).
      Similar analysis, performed on 28 temporal (prior and current) pairs, resulted in
      a good correlation coefficient [Formula: see text] ([Formula: see text]) for
      prior and [Formula: see text] ([Formula: see text]) for current cases. The
      developed framework showed prospects to help radiologists to perform an
      assessment of ABUS lesion volumes, as well as to quantify volumetric changes
      during lesions diagnosis and follow-up.

PMID- 29182057
TI  - The new Chikungunya virus outbreak in Italy possibly originated from a single
      introduction from Asia.

PMID- 29182059
TI  - Upcoming RANZCP conferences.

PMID- 29182058
TI  - Prevalence and antimicrobial susceptibility of Ureaplasma species and Mycoplasma
      hominis in Greek female outpatients, 2012-2016.
AB  - Mycoplasma hominis and Ureaplasma species are opportunistic pathogens associated
      with urogenital infections, complications during pregnancy and postpartum
      infections. Appropriate empirical antimicrobial treatment is necessary to achieve
      an optimal therapeutic outcome. This study evaluated the prevalence and the
      antimicrobial susceptibility of Mycoplasma hominis and Ureaplasma spp. isolated
      from 1,008 endocervical samples of outpatients in Crete, Greece, during a five
      year period (2012-2016), using the commercially available Mycoview kit (Zeakon
      diagnostics, France). Ureaplasma spp. was isolated from 116 patients (11.5%), M.
      hominis from 6 (0.6%), while coinfection with both mycoplasmas was demonstrated
      in 17 (1.7%). All Ureaplasma strains were susceptible to josamycin and
      doxycycline. Doxycycline, minocycline and ofloxacin were the most potent
      antibiotics against M. hominis. Docycycline was proved the most active and is
      still the drug of choice for the treatment of genital mycoplasma infections.
      Local surveillance to monitor changes in antimicrobial susceptibilities is
      necessary to guide treatment strategies.

PMID- 29182062
TI  - Shared decision-making in psychiatry of old age.

PMID- 29182063
TI  - Mediating assertive care and paternalism in old age psychiatry - An interview
      with Gary Cheung.

PMID- 29182064
TI  - Seton therapy.

PMID- 29182065
TI  - Violence in severe mental illness: is cognition missing in the associations with
      ethnicity, cannabis and alcohol?

PMID- 29182067
TI  - Contemporary mental health care and the role of psychiatrists.

PMID- 29182066
TI  - "Atomic psychiatry? An essay" by Ian Patrick (Paddy) Burges Watson.

PMID- 29182068
TI  - Can clinical subtypes contribute to genetic studies on major depression?

PMID- 29182069
TI  - From the President.

PMID- 29182070
TI  - Talking with Dr Giles Newton-Howes.

PMID- 29182073
TI  - New Zealand National Conference 2017: Kia Kotahi ai nga- Ara - Uniting the
      Pathways.

PMID- 29182072
TI  - Aboriginal and Torres Strait Islander Fellow and trainee forum.

PMID- 29182074
TI  - Enclosure design for flock-level, chronic exposure of birds to air contaminant
      mixtures.
AB  - The objective of this study was to design an enclosure suitable for studying the
      ecotoxicological effects of vehicle emissions on groups of wild birds without
      compromising welfare. Two, adjacent enclosures sheltered from sunlight, wind and
      rain, were bird-proofed and wrapped with thick polyethylene sheeting. Emissions
      were directed into the treatment enclosure from the exhaust of a light-duty
      gasoline truck, using flexible, heat-proof pipe, with joins sealed to prevent
      leakage. During active exposure, the engine was idled for 5 h/day, 6 days/week
      for 4 weeks. Fans maintained positive pressure (controls) and negative pressure
      (treatment), preventing cross-contamination of enclosures and protecting
      investigators. Four sets of passive, badge-type samplers were distributed across
      each enclosure, measuring nitrogen dioxide, sulfur dioxide and volatile organic
      compounds (NO2, SO2 and VOCs, respectively), and were complemented by active
      monitors measuring VOCs and particulate matter (2.5 um diameter, PM2.5). We found
      that the concentrations of NO2, SO2 and PM2.5 were not different between
      treatment and control enclosures. Volatile organic compounds (e.g. benzene,
      toluene, ethylbenzene and xylenes) were approximately six times higher in the
      treatment enclosure than control (13.23 and 2.13 ug m-1, respectively). In
      conclusion, this represents a successful, practical design for studying the
      effects of sub-chronic to chronic exposure to realistic mixtures of vehicle
      exhaust contaminants, in groups of birds. Recommended modifications for future
      research include a chassis dynamometer (vehicle treadmill), to better replicate
      driving conditions including acceleration and deceleration.

PMID- 29182075
TI  - Tricyclic and selective serotonin-reuptake-inhibitor antidepressants compared
      with placebo in randomized trials for acute major depression.

PMID- 29182077
TI  - The journal of mental health would like to thank the following reviewers who have
      contributed to the issues in 2017.

PMID- 29182076
TI  - No evidence for an acute placebo effect on emotional processing in healthy
      volunteers.
AB  - Placebo-controlled trials are the gold standard measure of efficacy in the
      development of new treatments for depression. However, the large placebo effects
      associated with standard measures of subjective symptoms reduce the sensitivity
      of such trials to detect antidepressant effects. There is a need to develop novel
      efficacy markers that are resistant to placebo effects. Measures of emotional
      processing, known to be sensitive to antidepressant treatment, may be such a
      marker, although the effect of an acute placebo treatment on these measures
      remains unclear. We assessed the influence of placebo on a validated battery of
      emotional processing tasks, the Emotional Test Battery (ETB), in healthy
      participants. Participants were informed they might receive the antidepressant
      drug bupropion, placebo or no treatment, with placebo effect being estimated as
      the difference between the placebo and no treatment groups. We found no
      significant difference between these groups on measures of emotional processing.
      There was also no effect of subjective treatment expectancy on performance in the
      tasks. This suggests that the ETB might be a useful tool for Phase I trials
      assessing novel antidepressant agents against placebo.

PMID- 29182078
TI  - Foodborne botulism in Poland in 2015
AB  - OBJECTIVE: The aim of this article is to assess the epidemiology of foodborne
      botulism in Poland in 2015compared to previous years MATERIALS AND METHODS: We
      reviewed (1) national surveillance data published in the annual
      bulletin"Infectious diseases and poisonings in Poland in 2015" and in previous
      publications, and (2) unpublished dataretrieved from botulism case reports for
      2015 sent from Sanitary-Epidemiological Stations to the Department ofEpidemiology
      NIPH-NIH. RESULTS: In 2015, a total of 30 foodborne botulism cases (including 18
      laboratory confirmed) was reported;the annual incidence rate (0.08 per 100,000
      population) was remarkably similar to that reported in previousyear and to the
      median incidence for years 2009 to 2013. The highest incidence in the country was
      reportedin Swietokrzyskie (0.24), Lubelskie (0.23) and Zachodniopomorskie
      province (0.23). Incidence in rural areas(0.13 per 100,000 population) was over 3
      times higher than the incidence in urban areas (0.04). Similarly, menhad more
      than 3 times higher incidence than women; As in previous year the highest
      incidence rate (0.30 per100,000 population) was observed among men in the age
      group of 20-24 years. Most cases were associated withconsumption of different
      types of commercially canned meat. Commercially produced canned fishery items
      werealso a common vehicle. All cases except one were hospitalized. No deaths
      related to the disease were reported. CONCLUSIONS: In 2015, the annual incidence
      of foodborne botulism in Poland was remarkably similar tothat reported in
      previous years. Since 2008 the number of foodborne botulism is stabilizing with
      an average of30 cases per year and corresponding incidence rate of 0.08 per
      100,000 population. It is important to conductthorough epidemiological
      investigation of each case, in order to identify the most common food vehicles
      forbotulism and other risk factors.

PMID- 29182079
TI  - Undulatory Swimming Performance and Body Stiffness Modulation in a Soft Robotic
      Fish-Inspired Physical Model.
AB  - Undulatory motion of the body is the dominant mode of locomotion in fishes, and
      numerous studies of body kinematics and muscle activity patterns have provided
      insights into the mechanics of swimming. However, it has not been possible to
      investigate how key parameters such as the extent of bilateral muscle activation
      affect propulsive performance due to the inability to manipulate muscle
      activation in live, freely swimming fishes. In this article we extend previous
      work on passive flexible mechanical models of undulatory propulsion by using
      actively controlled pneumatic actuators attached to a flexible foil to gain
      insight into undulatory locomotion and mechanisms for body stiffness control. Two
      soft actuators were attached on each side of a flexible panel with stiffness
      comparable to that of a fish body. To study how bilateral contraction can be used
      to modify axial body stiffness during swimming, we ran a parameter sweep of
      actuator contraction phasing and frequency. Thrust production by the soft
      pneumatic actuators was tested at cyclic undulation frequencies ranging from 0.3
      to 1.2 Hz in a recirculating flow tank at flow speeds up to 28 cm/s. Overall,
      this system generated more thrust at higher tail beat frequencies, with a plateau
      in thrust above 0.8 Hz. Self-propelled speed was found to be 0.8 foil lengths per
      second or ~13 cm/s when actuated at 0.55 Hz. This active pneumatic model is
      capable of producing substantial trailing edge amplitudes with a maximum
      excursion equivalent to 1.4 foil lengths, and of generating considerable thrust.
      Altering the extent of bilateral co-contraction in a range from -22% to 17% of
      the cycle period showed that thrust was maximized with some amount of
      simultaneous left-right actuation of ~3% to 6% of the cycle period. When the
      system is exposed to water flow, thrust was substantially reduced for conditions
      of greatest antagonistic overlap in left-right actuation, and also for the
      largest latencies introduced. This experimental platform provides a soft robotic
      testbed for studying aquatic propulsion with active control of undulatory
      kinematics.

PMID- 29182080
TI  - Arthrobots.
AB  - This article describes a class of robots-"arthrobots"-inspired, in part, by the
      musculoskeletal system of arthropods (spiders and insects, inter alia).
      Arthrobots combine mechanical compliance, lightweight and simple construction,
      and inexpensive yet scalable design. An exoskeleton, constructed from thin
      organic polymeric tubes, provides lightweight structural support. Pneumatic
      joints modeled after the hydrostatic joints of spiders provide actuation and
      inherent mechanical compliance to external forces. An inflatable elastomeric tube
      (a "balloon") enables active extension of a limb; an opposing elastic tendon
      enables passive retraction. A variety of robots constructed from these structural
      elements demonstrate (i) crawling with one or two limbs, (ii) walking with four
      or six limbs (including an insect-like triangular gait), (iii) walking with eight
      limbs, or (iv) floating and rowing on the surface of water. Arthrobots are simple
      to fabricate and are able to operate safely in contact with humans.

PMID- 29182081
TI  - Soft, Rotating Pneumatic Actuator.
AB  - This article describes a soft pneumatic actuator that generates cyclical motion.
      The actuator consists of several (three, four, or five) chambers (arranged around
      the circumference of a circle surrounding a central rod) that can be actuated
      independently using negative pressure (or partial vacuum). Sequential actuation
      of the four-chamber device using reduced pressure moves the central rod
      cyclically in an approximately square path. We characterize the trajectory of the
      actuator and the force exerted by it, as we vary the material used for
      fabrication, the number of chambers, and the size of the actuator. We demonstrate
      two applications of this actuator: to deliver fluid while stirring (by replacing
      the central rod with a needle) and for locomotion that mimics a reptilian gait
      (by combining four actuators together).

PMID- 29182082
TI  - Stiffness Customization and Patterning for Property Modulation of Silicone-Based
      Soft Pneumatic Actuators.
AB  - Soft pneumatic actuators (SPAs), as novel types of motion drivers for robotic
      devices, excel in many applications, such as rehabilitation and biomimicry, which
      demand compliance and softness. To further expand their scope of utilization, the
      SPAs should be customizable to meet the distinctive requirements of different
      applications. This article proposes a novel perspective on the SPA working
      mechanism based on stiffness distribution and then presents a versatile method
      called stiffness customization and patterning (SCP) for SPA body stiffness layout
      as a novel attempt to customize SPAs with distinctive properties. We fabricated a
      hybrid type of material combining unstretchable material and silicone with
      customizable aggregated elasticity. The tensile results showed that embedding
      unstretchable material directly increases the stiffness of the hybrid material
      sample, and our stress-strain model for SCP is able to adequately predict the
      elasticity of hybrid samples with specific material ratios. By applying this
      approach to bending-type SPAs, we are able to mitigate SPA buckling, a main
      failure mode of SPAs, and improve the SPA tip force by using hybrid material with
      globally increased stiffness. We also diversify bending modalities with different
      stiffness configurations in the hybrid material. SCP offers numerous ways to
      engineer SPAs for more applications.

PMID- 29182085
TI  - Learning Closed Loop Kinematic Controllers for Continuum Manipulators in
      Unstructured Environments.
AB  - This article introduces a machine-learning-based approach for closed loop
      kinematic control of continuum manipulators in the task space. For this purpose,
      we propose a unique formulation for learning the inverse kinematics of a
      continuum manipulator while integrating end-effector feedback. We demonstrate
      that this model-free approach for kinematic control is very well suited for
      nonlinear stochastic continuum robots. The article addresses problems that are
      vital for practical realization of machine-learning techniques. The primary
      objective is to solve the redundancy problem while making the algorithm scalable,
      fast, and tolerant to stochasticity, requiring minimal sensor elements and
      involving few open parameters for tuning. In addition, we demonstrate that the
      proposed controller can exhibit adaptive behavior in the presence of external
      forces and in an unstructured environment with the help of the morphological
      properties of the manipulator. Experimental validation of the proposed controller
      is done on a six-degree-of-freedom tendon-driven manipulator for pose control of
      the end effector in three-dimensional space with and without external forces. The
      experimental results exhibit accurate, reliable, and adaptive behavior of the
      proposed system, which appears suitable for the field of continuum service
      robots.

PMID- 29182084
TI  - Omni Directional Multimaterial Soft Cylindrical Actuator and Its Application as a
      Steerable Catheter.
AB  - Soft actuators with complex range of motion lead to strong interest in applying
      devices like biomedical catheters and steerable soft pipe inspectors. To
      facilitate the use of soft actuators in devices where controlled, complex,
      precise, and fast motion is required, a structurally controlled Omni directional
      soft cylindrical actuator is fabricated in a modular way using multilayer
      composite of polylactic acid based conductive Graphene, shape memory polymer,
      shape memory alloy, and polyurethane. Multiple fabrication techniques are
      discussed step by step that mainly include fused deposition modeling based 3D
      printing, dip coating, and UV curing. A mathematical control model is used to
      generate patterned electrical signals for the Omni directional deformations.
      Characterizations like structural control, bending, recovery, path, and thermal
      effect are carried out with and without load (10 g) to verify the new cylindrical
      design concept. Finally, the application of Omni directional actuator as a
      steerable catheter is explored by fabricating a scaled version of carotid artery
      through 3D printing using a semitransparent material.

PMID- 29182083
TI  - An Implantable Extracardiac Soft Robotic Device for the Failing Heart: Mechanical
      Coupling and Synchronization.
AB  - Soft robotic devices have significant potential for medical device applications
      that warrant safe synergistic interaction with humans. This article describes the
      optimization of an implantable soft robotic system for heart failure whereby soft
      actuators wrapped around the ventricles are programmed to contract and relax in
      synchrony with the beating heart. Elastic elements integrated into the soft
      actuators provide recoiling function so as to aid refilling during the diastolic
      phase of the cardiac cycle. Improved synchronization with the biological system
      is achieved by incorporating the native ventricular pressure into the control
      system to trigger assistance and synchronize the device with the heart. A three
      state electro-pneumatic valve configuration allows the actuators to contract at
      different rates to vary contraction patterns. An in vivo study was performed to
      test three hypotheses relating to mechanical coupling and temporal
      synchronization of the actuators and heart. First, that adhesion of the actuators
      to the ventricles improves cardiac output. Second, that there is a contraction
      relaxation ratio of the actuators which generates optimal cardiac output. Third,
      that the rate of actuator contraction is a factor in cardiac output.

PMID- 29182086
TI  - A Definition of Soft Materials for Use in the Design of Robots.

PMID- 29182087
TI  - Optimizing Double-Network Hydrogel for Biomedical Soft Robots.
AB  - Double-network hydrogel with standardized chemical parameters demonstrates a
      reasonable and viable alternative to silicone in soft robotic fabrication due to
      its biocompatibility, comparable mechanical properties, and customizability
      through the alterations of key variables. The most viable hydrogel sample in our
      article shows tensile strain of 851% and maximum tensile strength of 0.273 MPa.
      The elasticity and strength range of this hydrogel can be customized according to
      application requirements by simple alterations in the recipe. Furthermore, we
      incorporated Agar/PAM hydrogel into our highly constrained soft pneumatic
      actuator (SPA) design and eventually produced SPAs with escalated capabilities,
      such as larger range of motion, higher force output, and power efficiency.
      Incorporating SPAs made of Agar/PAM hydrogel resulted in low viscosity, thermos
      reversibility, and ultralow elasticity, which we believe can help to combine with
      the other functions of hydrogel, tailoring a better solution for fabricating
      biocompatible soft robots.

PMID- 29182088
TI  - Perinatal Maternal Mortality in Sickle Cell Anemia: Two Case Reports and Review
      of the Literature.
AB  - As outcomes of patients with sickle cell anemia improve and survival into
      adulthood with good quality of life and expectation of long-term survival becomes
      more common, challenges have developed, including issues related to reproduction.
      Pregnancy is frequently complicated in patients with sickle cell anemia with
      mortality up to 4.0%. Here we report maternal perinatal mortality in two women
      with sickle cell anemia who died post-partum due to acute chest syndrome (ACS),
      caused by bone marrow fat embolism and review the literature pertinent to this
      subject. Patient A was a 28-year-old woman with sickle cell anemia with multiple
      complications. At 30 weeks' gestation she developed hemolysis associated with
      poor placental function necessitating delivery by C-section. The fetus was
      delivered successfully but she died due to multi organ failure after delivery.
      Autopsy showed pulmonary and amniotic fluid embolization. Patient B was a 37-year
      old woman with uncomplicated sickle cell anemia who presented with pre term labor
      and crisis, then ACS and fetal distress. The infant was delivered successfully
      but the patient died after cardiovascular collapse. Autopsy results showed fat
      and bone marrow embolization as the cause of death. Pregnancy continues to be
      high risk for patients with sickle cell anemia including those with mild disease.
      Maternal perinatal mortality could be unpredictable due to serious complications
      of sickle cell disease. More studies to assess maternal perinatal mortality are
      needed.

PMID- 29182089
TI  - Investigation of the arterial intima-media thickness in Behcet's disease patients
      without vascular complaints.
AB  - Objectives Behcet's disease is a multisystemic, inflammatory disease. Various
      factors have been implicated in the disease, including genetics, infections,
      immunoglobulins, immune complexes, antibodies, and oxidative stress. However, the
      underlying etiopathogenesis remains unclear. Behcet's disease can occur with or
      without vascular involvement. This prospective study investigated the
      relationship between the intima-media thickness of the major arteries, in
      addition to other factors affecting the disease process, in Behcet's disease
      without vascular involvement. Methods Twenty-four patients (average age: 38.50 +/
      10.931) without vascular involvement or any vascular complaints who were
      diagnosed with Behcet's disease were included in the study. Sixteen healthy
      subjects (average age: 39.75 +/- 7.793) were included as a control group.
      Demographic information and medical histories were recorded, and routine blood
      tests were performed in both groups. The intima-media thickness of the
      subclavian, axillary, femoral, and carotid arteries of all the participants were
      recorded using Doppler ultrasonography. The data were then subjected to
      intergroup statistical and correlation analyses. Results There were no
      significant differences between the arterial intima-media thickness values of the
      Behcet's disease patients and those of the control group ( p > 0.05). However,
      there was a significant difference between the neutrophil-lymphocyte ratio ( p =
      0.004), low-density lipoprotein ( p = 0.007), and triglyceride ( p = 0042) levels
      of the two groups. Significant correlations were found between intima-media
      thickness and neutrophil-lymphocyte ratio levels ( p = 0.012) and the disease
      duration ( p = 0.030). There was also a significant correlation between the
      intima-media thickness of the femoral artery and disease duration ( p = 0.014).
      Conclusions The results showed that the duration of illness had a significant
      effect on arterial intima-media thickness in Behcet's disease. Blood neutrophil
      lymphocyte ratio levels were also associated with increased intima-media
      thickness.

PMID- 29182090
TI  - The Tactile Ethics of Soft Robotics: Designing Wisely for Human-Robot
      Interaction.
AB  - Soft robots promise an exciting design trajectory in the field of robotics and
      human-robot interaction (HRI), promising more adaptive, resilient movement within
      environments as well as a safer, more sensitive interface for the objects or
      agents the robot encounters. In particular, tactile HRI is a critical dimension
      for designers to consider, especially given the onrush of assistive and companion
      robots into our society. In this article, we propose to surface an important set
      of ethical challenges for the field of soft robotics to meet. Tactile HRI
      strongly suggests that soft-bodied robots balance tactile engagement against
      emotional manipulation, model intimacy on the bonding with a tool not with a
      person, and deflect users from personally and socially destructive behavior the
      soft bodies and surfaces could normally entice.

PMID- 29182091
TI  - Toward Modular Soft Robotics: Proprioceptive Curvature Sensing and Sliding-Mode
      Control of Soft Bidirectional Bending Modules.
AB  - Real-world environments are complex, unstructured, and often fragile. Soft
      robotics offers a solution for robots to safely interact with the environment and
      human coworkers, but suffers from a host of challenges in sensing and control of
      continuously deformable bodies. To overcome these challenges, this article
      considers a modular soft robotic architecture that offers proprioceptive sensing
      of pressure-operated bending actuation modules. We present integrated custom
      magnetic curvature sensors embedded in the neutral axis of bidirectional bending
      actuators. We describe our recent advances in the design and fabrication of these
      modules to improve the reliability of proprioceptive curvature feedback over our
      prior work. In particular, we study the effect of dimensional parameters on
      improving the linearity of curvature measurements. In addition, we present a
      sliding-mode controller formulation that drives the binary solenoid valve states
      directly, giving the control system the ability to hold the actuator steady
      without continuous pressurization and depressurization. In comparison to other
      methods, this control approach does not rely on pulse width modulation and hence
      offers superior dynamic performance (i.e., faster response rates). Our
      experimental results indicate that the proposed soft robotic modules offer a
      large range of bending angles with monotonic and more linear embedded curvature
      measurements, and that the direct sliding-mode control system exhibits improved
      bandwidth and a notable reduction in binary valve actuation operations compared
      to our earlier iterative sliding-mode controller.

PMID- 29182092
TI  - Preliminary Assessment of a Compliant Gait Exoskeleton.
AB  - Current commercial wearable gait exoskeletons contain joints with stiff actuators
      that cannot adapt to unpredictable environments. These actuators consume a
      significant amount of energy, and their stiffness may not be appropriate for safe
      human-machine interactions. Adjustable compliant actuators are being designed and
      implemented because of their ability to minimize large forces due to shocks, to
      safely interact with the user, and to store and release energy in passive elastic
      elements. Introduction of such compliant actuation in gait exoskeletons, however,
      has been limited by the larger power-to-weight and volume ratio requirement. This
      article presents a preliminary assessment of the first compliant exoskeleton for
      children. Compliant actuation systems developed by our research group were
      integrated into the ATLAS exoskeleton prototype. The resulting device is a
      compliant exoskeleton, the ATLAS-C prototype. The exoskeleton is coupled with a
      special standing frame to provide balance while allowing a semi-natural gait.
      Experiments show that when comparing the behavior of the joints under different
      stiffness conditions, the inherent compliance of the implemented actuators showed
      natural adaptability during the gait cycle and in regions of shock absorption.
      Torque tracking of the joint is achieved, identifying the areas of loading
      response. The implementation of a state machine in the control of knee motion
      allowed reutilization of the stored energy during deflection at the end of the
      support phase to partially propel the leg and achieve a more natural and free
      swing.

PMID- 29182093
TI  - Bioinspired Robotic Fingers Based on Pneumatic Actuator and 3D Printing of Smart
      Material.
AB  - In this article, we have proposed a novel robotic finger design principle aimed
      to address two challenges in soft pneumatic grippers-the controllability of the
      stiffness and the controllability of the bending position. The proposed finger
      design is composed of a 3D printed multimaterial substrate and a soft pneumatic
      actuator. The substrate has four polylactic acid (PLA) segments interlocked with
      three shape memory polymer (SMP) joints, inspired by bones and joints in human
      fingers. By controlling the thermal energy of an SMP joint, the stiffness of the
      joints is modulated due to the dramatic change in SMP elastic modulus around its
      glass transition temperature (Tg). When SMP joints are heated above Tg, they
      exhibit very small stiffness, allowing the finger to easily bend around the SMP
      joints if the attached soft actuator is actuated. When there is no force from the
      soft actuator, shape recovery stress in SMP contributes to the finger's shape
      restoration. Since each joint's rotation can be individually controlled, the
      position control of the finger is made possible. Experimental analysis has been
      conducted to show the finger's variable stiffness and the result is compared with
      the analytical values. It is found that the stiffness ratio can be 24.9 times for
      a joint at room temperature (20 degrees C) and at an elevated temperature of 60
      degrees C when air pressure p of the soft actuator is turned off. Finally, a
      gripper composed of two fingers is fabricated for demonstration.

PMID- 29182094
TI  - Origami Wheel Transformer: A Variable-Diameter Wheel Drive Robot Using an Origami
      Structure.
AB  - A wheel drive mechanism is simple, stable, and efficient, but its mobility in
      unstructured terrain is seriously limited. Using a deformable wheel is one of the
      ways to increase the mobility of a wheel drive robot. By changing the radius of
      its wheels, the robot becomes able to pass over not only high steps but also
      narrow gaps. In this article, we propose a novel design for a variable-diameter
      wheel using an origami-based soft robotics design approach. By simply folding a
      patterned sheet into a wheel shape, a variable-diameter wheel was built without
      requiring lots of mechanical parts and a complex assembly process. The wheel's
      diameter can change from 30 to 68 mm, and it is light in weight at about 9.7 g.
      Although composed of soft materials (fabrics and films), the wheel can bear more
      than 400 times its weight. The robot was able to change the wheel's radius in
      response to terrain conditions, allowing it to pass over a 50-mm gap when the
      wheel is shrunk and a 50-mm step when the wheel is enlarged.

PMID- 29182095
TI  - Fin Ray Stiffness and Fin Morphology Control Ribbon-Fin-Based Propulsion.
AB  - Ribbon-fin-based propulsion has rich locomotor capabilities that can enhance the
      mobility and performance of underwater vehicles navigating in complex
      environments. Bony fishes using this type of propulsion send one or multiple
      traveling waves along an elongated fin with the actuation of highly flexible rays
      that are interconnected by an elastic membrane. In this work, we study how the
      use of flexible rays and different morphology can affect the performance of
      ribbon-fin propulsion. We developed a physical model composed of 15 rays that are
      interconnected with an elastic membrane. We tested four different ray flexural
      stiffness and four aspect ratios. The robotic model was tested in a low
      turbulence flume under two flow conditions ([Formula: see text] wavelength/s). In
      two experimental sets, we measured fin kinematics, net surge forces, and power
      consumption. Using these data, we perform a thrust and power analysis of the
      undulating fin. We present the thrust coefficient, power coefficient, and
      propulsive efficiency. We find that the thrust generation was linear with the
      enclosed area swept by the fin, and square of the relative velocity between the
      incoming flow and traveling wave. The thrust coefficient levels off around 0.5.
      In addition, for our parameter range, we find that the power consumption scales
      by the cube of the effective tangential velocity of the rays [Formula: see text]
      (A is the amplitude of the ray oscillating motion, and [Formula: see text] is the
      angular velocity). We show that a decay in stiffness decreases both thrust
      production and power consumption. However, for rays with high flexural stiffness,
      the difference in thrust compared with rigid rays is minimal. Moreover, our
      results show that flexible rays can improve the propulsive efficiency compared
      with a rigid counterpart. Finally, we find that the morphology of ribbon fin
      affects its propulsive efficiency. For the aspect ratio considered in our
      experiments, [Formula: see text] was the most efficient compared with [Formula:
      see text]. Our results suggest that there could be an optimal morphology for a
      given ribbon fin kinematics. Therefore, both natural swimmers and underwater
      vehicles using ribbon-fin-based propulsion can take advantage of flexible rays
      and optimal aspect ratio to improve propulsive performance.

PMID- 29182096
TI  - Leveraging Internal Viscous Flow to Extend the Capabilities of Beam-Shaped Soft
      Robotic Actuators.
AB  - Elastic deformation of beam-shaped structures due to embedded fluidic networks
      (EFNs) is mainly studied in the context of soft actuators and soft robotic
      applications. Currently, the effects of viscosity are not examined in such
      configurations. In this work, we introduce an internal viscous flow and present
      the extended range of actuation modes enabled by viscosity. We analyze the
      interaction between elastic deflection of a slender beam and viscous flow in a
      long serpentine channel embedded within the beam. The embedded network is
      positioned asymmetrically with regard to the neutral plane and thus pressure
      within the channel creates a local moment deforming the beam. Under assumptions
      of creeping flow and small deflections, we obtain a fourth-order integro
      differential equation governing the time-dependent deflection field. This
      relation enables the design of complex time-varying deformation patterns of beams
      with EFNs. Leveraging viscosity allows to extend the capabilities of beam-shaped
      actuators such as creation of inertia-like standing and moving wave solutions in
      configurations with negligible inertia and limiting deformation to a small
      section of the actuator. The results are illustrated experimentally.

PMID- 29182097
TI  - A Practical Approach to Soft Actuation.

PMID- 29182098
TI  - The JamHand: Dexterous Manipulation with Minimal Actuation.
AB  - From using chopsticks to grab items off a plate, to snapping together two LEGO
      bricks in one hand, common manipulation tasks are easy for humans. However,
      grasping and dexterous manipulation still rank among the principal grand
      challenges in robotics. A key challenge is the complex interaction between hand
      biomechanics and motor control, leading to humanoid hands that remain too complex
      and costly for use in daily tasks. Here, we bypass this challenge by offering an
      alternative approach based on multi-finger material phase transition effects. By
      limiting our focus to dexterous manipulation, we are able to design a robotic
      hand that can achieve six fundamental dexterous manipulations as well as
      precision and power grasps, all with only two actuators. We further demonstrate
      our system on a range of real-world grasping and manipulation challenges. Besides
      practical application, these results suggest that leveraging the phase transition
      of granular materials is a viable technique for reducing the hand complexity
      required for performing daily tasks.

PMID- 29182099
TI  - An Overview of Shape Memory Alloy-Coupled Actuators and Robots.
AB  - The one-dimensional deformation of shape memory alloy (SMA) wires and springs can
      be implemented into different types of functional structures with three
      dimensional deformations. These structures can be classified based on the type of
      structure and how the SMA element has been implemented into the following
      categories: rigid mechanical joints, semi-rigid flexural hinges, SMA elements
      externally attached to a soft structure, and embedded into the soft structure.
      These structures have a wide range of properties and implementation requirements,
      and they have been used to produce a variety of robots with rigid and soft
      motions. The different research efforts to develop actuators and robots related
      to each type of structure are presented along with their respective strengths and
      weaknesses. A model is then developed to discuss the performance and
      applicability of SMA wires versus SMA springs for actuators with a polymeric
      matrix to see the effect of each type of SMA on the selection of design
      parameters. A comparison of the different types of structures and the
      applicability of different types of SMA elements for different types of
      structures is then presented.

PMID- 29182100
TI  - Dielectric Elastomer Actuators for Soft Wave-Handling Systems.
AB  - This article presents a soft handling system inspired by the principle of the
      natural wave (named Wave-Handling system) aiming to offer a soft solution to
      delicately transport and sort fragile items such as fruits, vegetables,
      biological tissues in food, and biological industries. The system consists of an
      array of hydrostatically coupled dielectric elastomer actuators (HCDEAs). Due to
      the electrostriction property of dielectric elastomers, the handling system can
      be controlled by electric voltage rather than the cumbersome pneumatic system. To
      study the working performance of the Wave-Handling system and how the performance
      can be improved, the basic properties of HCDEA are investigated through
      experiments. We find that the HCDEA exhibits some delay and hysteretic
      characteristics when activated by periodic voltage and the characteristics are
      influenced by the frequency and external force also. All this will affect the
      performance of the Wave-Handling system. However, the electric control, simple
      structure, light weight, and low cost of the soft handling system show great
      potential to move from laboratory to practical application. As a proof of design
      concept, a simply made prototype of the handling system is controlled to generate
      a parallel moving wave to manipulate a ball. Based on the experimental results,
      the improvements and future work are discussed and we believe this work will
      provide inspiration for soft robotic engineering.

PMID- 29182101
TI  - Design and Fabrication of Soft Morphing Ray Propulsor: Undulator and Oscillator.
AB  - A soft morphing ray propulsor capable of generating an undulating motion in its
      pectoral fins was designed and fabricated. The propulsor used shape memory alloy
      for actuation, and the body was made with soft polymers. To determine the effects
      of undulation in the fins, two models that differed in terms of the presence of
      undulation were fabricated using different polymer materials. The experimental
      models were tested with a dynamometer to measure and compare thrust tendencies.
      Thrust measurements were conducted with various fin beat frequencies. Using the
      experimental data, the concept of an optimized standalone version of the ray
      robot was suggested and its prototype was fabricated. The fabricated robot was
      able to swim as fast as 0.26 body length per second and 38% more efficient than
      other smart material-based ray-like underwater robots.

PMID- 29182102
TI  - A Novel Concept for Safe, Stiffness-Controllable Robot Links.
AB  - The recent decade has seen an astounding increase of interest and advancement in
      a new field of robotics, aimed at creating structures specifically for the safe
      interaction with humans. Softness, flexibility, and variable stiffness in
      robotics have been recognized as highly desirable characteristics for many
      applications. A number of solutions were proposed ranging from entirely soft
      robots (such as those composed mainly from soft materials such as silicone), via
      flexible continuum and snake-like robots, to rigid-link robots enhanced by joints
      that exhibit an elastic behavior either implemented in hardware or achieved
      purely by means of intelligent control. Although these are very good solutions
      paving the path to safe human-robot interaction, we propose here a new approach
      that focuses on creating stiffness controllability for the linkages between the
      robot joints. This article proposes a replacement for the traditionally rigid
      robot link-the new link is equipped with an additional capability of stiffness
      controllability. With this added feature, a robot can accurately carry out
      manipulation tasks (high stiffness), but can virtually instantaneously reduce its
      stiffness when a human is nearby or in contact with the robot. The key point of
      the invention described here is a robot link made of an airtight chamber formed
      by a soft and flexible, but high-strain resistant combination of a plastic mesh
      and silicone wall. Inflated with air to a high pressure, the mesh silicone
      chamber behaves like a rigid link; reducing the air pressure, softens the link
      and rendering the robot structure safe. This article investigates a number of
      link prototypes and shows the feasibility of the new concept. Stiffness tests
      have been performed, showing that a significant level of stiffness can be
      achieved-up to 40 N reaction force along the axial direction, for a 25-mm
      diameter sample at 60 kPa, at an axial deformation of 5 mm. The results confirm
      that this novel concept to linkages for robot manipulators exhibits the beam-like
      behavior of traditional rigid links when fully pressurized and significantly
      reduced stiffness at low pressure. The proposed concept has the potential to
      easily create safe robots, augmenting traditional robot designs.

PMID- 29182103
TI  - Association of mitochondrial copy number variation and T16189C polymorphism with
      colorectal cancer in North Indian population.
AB  - Globally, colorectal cancer is the third most common type of cancer. Genetic
      instability leading to cancer development is one of the major causes for
      development of cancer. Alterations in mitochondrial genome, that is, mutations,
      single-nucleotide polymorphisms, and copy number variations are known to
      contribute in cancer development. The aim of our study was to investigate
      association of mitochondrial T16189C polymorphism and copy number variation with
      colorectal cancer in North Indian population. DNA isolated from peripheral blood
      of 126 colorectal cancer patients and 114 healthy North Indian subjects was
      analyzed for T16189C polymorphism and half of them for mitochondrial copy number
      variation. Genotyping was done using polymerase chain reaction-restriction
      fragment length polymorphism, and copy number variation was estimated using real
      time polymerase chain reaction, numbers of mitochondrial copies and found to be
      significantly higher in colorectal cancer patients than healthy controls (88 (58
      154), p = 0.001). In the regression analysis, increased mitochondrial copy number
      variation was associated with risk of colorectal cancer (odds ratio = 2.885, 95%
      confidence interval = 1.3-6.358). However, T16189C polymorphism was found to be
      significantly associated with the risk of rectal cancer (odds ratio = 5.213, p =
      0.001) and non-significantly with colon cancer (odds ratio = 0.867, p = 0.791).
      Also, false-positive report probability analysis was done to validate the
      significant findings. Our results here indicate that mitochondrial copy number
      variation may be playing an important role in the development of colorectal
      cancer, and detection of mitochondrial copy number variation can be used as a
      biomarker for predicting the risk of colorectal cancer in North Indian subjects.

PMID- 29182104
TI  - Steered molecular dynamics for studying ligand unbinding of ecdysone receptor.
AB  - Ecdysone receptor (EcR) is an important target for pesticide design. Ligand
      binding regulates EcR transcriptional activity similar to other nuclear
      receptors; however, the pathways by which ligands enter and leave the EcR remain
      poorly understood. Here, we performed computational studies to identify unbinding
      pathways of an ecdysone agonist [the selective ecdysone agonist, BYI06830] from
      the EcR ligand binding domain (EcR LBD). BYI06830 can dissociate from EcR LBD via
      four different pathways with little effect on receptor structure. By comparing
      the potential of mean force (PMF) of four pathways, path 2 was considered to be
      the most likely exit path for BYI06830, which was located in the cleft formed by
      the H3-H4 loop, H6-H7 loop, and the H11 C-terminus. Furthermore, structural
      features along path 2 were analyzed and the structural snapshots of the
      metastable and transition states were isolated to illustrate the unbinding
      mechanism of ecdysone agonist from EcR LBD.

PMID- 29182105
TI  - A meta-analysis of external fixation and flexible intramedullary nails for
      femoral fractures in children.
AB  - Background : The purpose of this meta-analysis was to compare the outcomes of
      external fixation and flexible intramedullary nails for femoral fractures in
      children between 5 and 15 years of age based on the current evidence. Materials
      and methods: We searched relevent studies in the following database: Cochrane
      library, PubMed and EMABASE up to May 2014. All randomized controlled trials,
      Clinical controlled trials and retrospective controlled studies comparing
      external fixation and flexible intramedullary nails in femoral fractures of
      children were included. Data was extracted independently for meta-analysis.
      Results: Seven trials altogether involving 338 cases of femoral fractures of
      children treated by external fixation (128 cases) and flexible intramedullary
      nails (210 cases) were included in the meta-analysis. Results showed that
      flexible intramedullary nails was superior to external fixation in less time to
      union , lower postoperative infection rate and refracture rate . It may not
      increase delayed union, Limb-length discrepancy , pain and bursitis . Both
      fixations obtained a similar patient satisfaction. conclusion: Flexible
      intramedullary nail had greater advantages for the treatment of femoral fractures
      in children aged 5-15 years, compared to external fixation based on current meta
      analysis. This conclusion will ultimately require rigorous and adequately powered
      randomized controlled trials to be proved.

PMID- 29182106
TI  - Multidisciplinary approach to osteosarcoma.
AB  - Osteosarcoma is a malignant bone tumor composed of mesenchymal cells producing
      osteoid and immature bone. Osteosarcoma is the most frequent primary malignant
      bone tumor, if we excluded myeloma, a haematologic disease. The incidence of
      osteosarcoma is 2-3/million/year, but is higher in adolescence, in which the
      annual incidence peaks at 8-11/million/year at 15-19 years of age. Local pain,
      followed by localized swelling and limitation of joint movement, are the typical
      signs and symptoms. Correct diagnosis can be achieved through a correct approach
      to the disease and the combination of clinical and radiographic aspects. The
      final step to confirm the diagnosis is the biopsy. Computer Tomography of the
      chest and Positron-Emission Tomography are mandatory to complete the staging,
      which is performed according the Musculoskeletal Tumor Society staging system. A
      multidisciplinary approach is needed both to get to a correct diagnosis
      (orthopaedic surgeon, radiologist and histopathologist) and to perform definitive
      treatment. Multidisciplinary approach should be performed in reference centers
      able to provide access to the full spectrum of care and where orthopaedic
      surgeon, oncologist, histopathologist, radiologist and radiotherapist can
      cooperate. The management of osteosarcoma is based primarily on neo-adjuvant and
      adjuvant chemotherapy and surgical resection; radiotherapy is not effective as
      osteosarcomas are relatively radioresistant. Prognostic factors include
      metastases at presentation, histologic response to induction chemotherapy, the
      site of the primary tumor (with axial lesions having an inferior outcome), serum
      lactate dehydrogenase and alkaline phosphatase levels.

PMID- 29182107
TI  - Displaced distal end radius fractures in children treated with Kirschner wires -
      A systematic review.
AB  - The indications for Kirschner wiring, the technique of wiring, type of cast
      immobilization, period of immobilization and complications of K wires are
      unclear. We conducted a systematic review of the literature on Kirschner wiring
      of distal radius fractures in children. A total of 4263 articles were identified.
      The full text of the remaining 78 articles was reviewed. 64 articles were finally
      excluded because of incomplete data leaving 14 for analysis. Complete fracture
      displacement and translation more than 50% are the commonest indications for
      Kirschner wiring of these fractures with 2 retrograde wires in non-Kapandji
      fashion being the commonest technique. Long arm casts are the favored modality of
      immobilization with superficial infection being the commonest complication. Re
      displacement rates are low after Kirschner wiring. Most studies were
      retrospective and there is the need for a multicenter randomized controlled trial
      to define protocols for management of displaced distal radius fractures in
      children.

PMID- 29182108
TI  - Triple pelvic osteotomy for the treatment of symptomatic acetabular dysplasia in
      adolescents and adults : A review of 42 hips.
AB  - We treated 42 hips with symptomatic acetabular dysplasia using triple pelvic
      osteotomy. The mean age of the patients was 20.7 years (12-47). The median follow
      up was 50.3 months. The average Harris hip score improved from 74 to 92 points.
      Significant improvement from the preoperative to the latest follow-up evaluation
      was seen radiologically with reference to the center-edge angle, the anterior
      center-edge angle, the acetabular index and the femoral head extrusion index.
      Shenton's line was intact in 9 hips before the operation and it was intact in 40
      hips at the latest follow-up. The cross-over sign was present in 15 hips before
      the operation and it was present in one hip after the operation. The results of
      this study demonstrated that triple pelvic osteotomy provides improved
      radiographic results and good symptomatic relief in acetabular dysplasia.

PMID- 29182109
TI  - Factors affecting outcome after the use of the Ponseti method for the management
      of idiopathic clubfoot, a retrospective study in an orthopaedic referral
      institute.
AB  - TIn the last few decades Ponseti method has replaced soft tissue releases as the
      gold standard in the management of idiopathic clubfoot. However, the recurrence
      of the deformity is common without post tenotomy bracing. The purpose of this
      study was to retrospectively see various attributes of the patients associated
      with poor outcome after use of Ponseti method in idiopathic clubfoot management.
      Seventy nine consecutive patients with one hundred and twenty three idiopathic
      clubfeet treated with Ponseti method by single orthopaedic surgeon were followed
      for a period of two years and recurrence of the deformity was studied in relation
      to age of patient at presentation (< 3 months or more), sex of the patient,
      severity of the deformity ( moderate to severe verses (Vs.) very severe),
      compliance to post tenotomy bracing (compliant Vs. non compliant), educational
      level of parents (high school or less) and access of parents to internet (Yes or
      No) and odds ratio for recurrence and level of significance determined for each
      using Fisher's exact t-test. Non compliance in seventeen patients (17.7%) with
      post tenotomy bracing was the most important factor related to the recurrence,
      with an odds ratio of 6.22 (P =0.0059). Educational level (less than high school)
      of parents (36.7%) was the second most important factor with odds ratio of 5.5
      (P=0.0073). Fifteen patients with severe Demiglio scoring feet had an odds ratio
      of 5.3 (P= 0.0097) for the recurrence of the deformity. Inaccess of the parents
      to the internet had an odds ratio of 6.33 (P =0.011) for the recurrence of the
      deformity. Age and sex of the patients was not found to have a significant effect
      on the recurrence of the deformity. In conclusion, the risk factors associated
      with recurrence of the idiopathic clubfoot deformity except severity of the
      deformity are modifiable and extra minutes can be spent with risk group parents
      during follow up visits to prevent a recurrence by making them understand natural
      history of the corrected foot without post tenotomy bracing, encouraging them for
      regular follow up visits, arranging interactive sessions with other patients who
      are regular in their follow up and compliant with bracing, and encouraging the
      literate parents to update their information about clubfoot from internet.

PMID- 29182110
TI  - Difference between Spinecor brace and Thoracolumbosacral orthosis for deformity
      correction and quality of life in adolescent idiopathic scoliosis.
AB  - Although there are several conservative treatment options, only bracing has been
      found to be effective in preventing curve progression and a subsequent need for
      surgery in adolescent idiopathic scoliosis. The objective of this study is to
      compare the results of SpineCor brace and thoracolumbosacral orthosis (TLSO) for
      treatment of adolescent idiopathic scoliosis radiologically and clinically. Sixty
      four patients with adolescent idiopathic scoliosis treated with brace included in
      this study. Height, T1-Coccygx distance, and gibbosity were measured. Rib hump
      deformity was evaluated with a scoliometer. An SRS-22 questionnaire was used to
      determine the quality of life of patients after the first year of brace
      treatment. Differences in Cobb angles and gibbosity were insignificant for both
      groups. SRS-22 questionnaire results showed significant differences in pain, self
      image and function/activity subgroups. Patients' mental health and satisfaction
      scores were insignificant. These braces have a similar effect on deformity
      correction. The surgery rates and success rates of braces are approximately
      equal. The major difference between SpineCor and TLSO is health-related quality
      of life.

PMID- 29182111
TI  - The effect of distraction-based growth-friendly spinal instrumentation on growth
      in early-onset scoliosis.
AB  - The present study assessed the advantages and disadvantages of growth-friendly
      spinal instrumentation surgery for early-onset scoliosis in 17 patients who
      underwent this surgery with a minimum 2-year follow-up. The mean number of
      lengthening procedures was three, initial age at which surgery was performed was
      108.1 +/- 30.2 months, and follow-up duration was 40.6 +/- 16.6 months. Spinal
      height (T1-S1 and T1-T12), lung space available, major Cobb angle for scoliosis,
      maximum thoracic kyphosis, lumbar lordosis, shoulder and pelvic balance, and
      coronal and sagittal balance were assessed preoperatively and at the last follow
      up. Treatment with growth-friendly spinal instrumentation showed evident
      increases in the spinal height and space available for the lungs, and significant
      improvement in scoliosis and thoracic kyphosis. The most commonly observed
      complications were proximal anchor problems and proximal junctional kyphosis. To
      avoid proximal junctional kyphosis in treatments with growing rods, excessive
      thoracic kyphosis correction should not be performed.

PMID- 29182112
TI  - Treatment outcome in 60 children with pathological fractures of the humerus
      caused by juvenile or aneurysmal bone cysts.
AB  - The treatment of pathological fractures of the humerus caused by juvenile or
      aneurysmal bone cysts (JBC/ABC) should be a single approach with a high success
      rate and low complication rate. This study evaluates how day by day treatment
      concepts fulfil these aims. Children below 15 years of age with a pathological
      fracture of the humerus caused by a JBC or ABC between 01.01.2001 and 31.12.2010,
      were investigated by chart review in four major paediatric trauma centres. Age,
      gender, fracture localisation, X-ray findings, treatment and outcome - assessed
      by the Capanna classification (I to IV), were analysed. 60 children [41male, 19
      female; mean age: 9 years (4-14 years)] with 43 JBC and 12 ABC were included as
      well as five cysts, who could not be classified definitively. First treatment was
      non-operatively in 33 children. Of these 27 cysts did not improve; likewise the
      supportive installation of cortisone in six patients did not change the outcome.
      The first treatment consisted of elastic stable intramedullary in 13 children; up
      to three nail exchanges included. But only six of these reached (nearly) complete
      resolution (I/II). Overall the combined mechanical and biological treatment with
      curettage, elastic stable intramedullary nailing, (artificial) bone substitute
      and in some cases growth factors was performed as the 1st-line treatment in nine
      patients and further in 2nd or 3rd-line treatments in 13 humeral cysts. More than
      half of these reached a complete or nearly complete resolution of the cyst (12x
      I, 5x II, 1x III, 4x IV). Major complications in all operated patients were six
      nails not removable and two children with upper extremities length differences.
      Healing rates are low for non-operative treatment, elastic stable intramedullary
      nailing alone and by using cortisone for cysts resolution in pathological
      fractures of the humerus. Data support a combined mechanical and biological
      treatment with curettage, elastic stable intramedullary nailing, (artificial)
      bone substitute and the use of growth factors.

PMID- 29182113
TI  - Fusion-segment of high-grade Lumbar Spondylolisthesis: 2-year follow-up.
AB  - The clinical efficacy of reduction and fusion surgery and the suitable range of
      fusion-segment were evaluated in 12 pediatric patients treated for high-grade
      spondylolisthesis. Pre/post-operative clinical and radiological assessments were
      analyzed. A transient L5 nerve root paralysis was observed in one patient with L5
      spondylolisthesis. No degenerative spondylolisthesis or adjacent segmental
      instability occurred above the fusion segments. In conclusion, we suggest that,
      in case of spondylolisthesis without severe structural scoliosis deformity or
      only associated with lumbosacral deformity, the posterior ligament complex should
      be protected in case of adjacent segmental instability and spondylolisthesis. If
      the spondylolisthesis is complicated with severe structural scoliosis deformity
      (Cobb >= 70 degrees ), in principle, the treatment should be performed according
      to the characteristics of the two diseases respectively.

PMID- 29182114
TI  - Assessment of the Medial Longitudinal Arch in children with Flexible Pes Planus
      by Plantar Pressure Mapping.
AB  - INTRODUCTION: Plantar Pressure mapping was introduced as a new modality for
      assessment of the height of the medial longitudinal arch of the foot. Therefore,
      the aim of this study is to correlate the plantar pressure mapping readings of
      arch index contact force ratio (AICFR) in children with flexible pes planus with
      radiographic measurements and static plantar footprints in order to determine the
      reliability of pressure mapping as a modality for the assessment and follow up of
      the flat foot deformity. PATIENTS AND METHODS: Radiographic measurements, foot
      prints, and pressure mapping scans were recorded for each foot at initial
      presentation and at latest follow up in 28 children (56 feet) with flexible pes
      planus. RESULTS: A positive correlation of pressure mapping results was found
      with the talo-first metatarsal angle, the calcaneal pitch angle, as well as the
      footprint scans (P < 0.001). CONCLUSION: This study demonstrated that plantar
      pressure mapping is a reliable and effective tool in screening, diagnosis, and
      follow up of children with flexible pes planus.

PMID- 29182115
TI  - Management of adolescent tibia vara using Taylor spatial frame.
AB  - PURPOSE: Adolescent tibia vara is a multiplanar deformity that can lead to
      progressive deformity, altered gait, unequal leg lengths, and premature knee
      arthritis if uncorrected. The purpose of the current study is to report our
      experience in management of adolescent tibia vara using Taylor Spatial Frame
      (TSF). MATERIALS AND METHODS: A prospective study of eleven adolescent tibia vara
      patients managed by proximal tibial osteotomy gradual deformity correction using
      TSF. RESULTS: The average time in the frame was 123.5 (+/-25.5) days. At final
      follow up (average 15 (+/-2) months), the mean post-operative mPTA was 87 (+/-4)
      degrees (range 81 to 93 degrees), where the mean preoperative mean mPTA was 68
      (+/-9) degrees (range 49 to 77 degrees) (p value 0.003). The mean postoperative
      MAD was 12.2(+/-11.4) mm, range (-1 to 26 mm), where preoperative mean MAD was
      75.7(+/-14.7 mm), range (60 to 107mm) (p value 0.003). The mean postoperative
      PPTA was 80(+/-2) degrees, range (77 to 83 degrees), while the preoperative mean
      PPTA was 72 (+/-12) degrees, range (42 to 82 degrees) (p value 0.028).
      CONCLUSION: Although we have not directly compared the TSF with the Ilizarov
      fixator, this series serves to highlight the versatility and effectiveness of the
      TSF in the treatment of complex and often obstinate adolescent tibia vara.

PMID- 29182116
TI  - Surgical treatment for developmental dysplasia of the hip- a single surgeon
      series of 47 hips with a 7 year mean follow up).
AB  - The treatment of developmental dysplasia of the hip (DDH) in children remains
      controversial. We describe the clinical and radiological outcomes of  47 hips in
      43 children treated with open surgery by one surgeon between 2004 and 2008 for
      DDH. The mean age at operation was 25 months (5 to 113) with a mean follow up of 
      89 months  (22 to 169). At the latest follow up 40 of the 45 hips where Severin
      grades were recordable (89%) were graded as excellent or good, Severin class I or
      II. Clinically significant AVN (grade II to III  according to the Kalamchi and
      MacEwen classification) was seen in 6  (13%) of the hips. We found a pelvic
      osteotomy to be a risk factor for AVN  (p 0.02) and age at operation to be a risk
      factor for poor morphology at final follow up (p 0.03). Over 18 months old a
      pelvic osteotomy should be performed in selective cases depending on intra
      operative stability, but we will now consider doing this as a staged procedure
      and delaying the osteotomy for a period of time after open reduction to reduce
      the risk of AVN.

PMID- 29182117
TI  - Osteochondral fractures of the knee in skeletally immature patients: short term
      results of operative fixation using Omnitech screws.
AB  - PURPOSE: Osteochondral fractures in skeletally immature patients are rare. A
      retrospective case series is reported looking at the use of Omnitech compression
      screws for these injuries. METHOD: Nine patients with a mean age of 14 were
      included in the study with a mean follow up of 26 months. RESULTS: The average
      KOOS, IKDC and Tegner Lysholm Scores were 86.7, 90.34 and 96.1 respectively.
      CONCLUSION: The use of Omnitech screws in the acute setting for skeletally
      immature patients shows excellent short-term outcomes.

PMID- 29182118
TI  - Aneurysmal bone cystic lesions: value of genomic studies.
AB  - Aneurysmal bone cystic (ABC) lesions can be primary or secondary (to a trauma or
      a pre-existing benign or malignant tumour). Specific translocations of the USP6
      gene are reported in about 70% of primary but never in secondary ABC lesions. We
      report two cases of ABC lesions in which imbalanced genomic aberrations were
      detected at initial presentation and showed complex clonal evolution. These
      demonstrative observations strengthen the guidelines regarding the diagnostic
      approach when an ABC is suggested by imaging. Biopsy is mandatory including
      genomic analysis. When a primary ABC is not clearly proven by the initial biopsy,
      an extensive curettage should be performed, with pathological examination of all
      removed tissue in order to exclude a secondary ABC. It also illustrates the added
      value of genomic analyses in the setting of an ABC lesion: complex clonal
      aberrations argues for a lesion secondary to a malignant proliferation whereas
      USP6 rearrangement allows the diagnosis of primary ABC.

PMID- 29182119
TI  - IA comparison of two minimally invasive procedures for intra-articular displaced
      calcaneal fractures in older children.
AB  - The purpose of this study was to compare the clinical outcomes of displaced intra
      articular calcaneal fractures in older children treated with poking reduction and
      cannulated screws fixation or with plate fixation using a sinus tarsi approach.
      From June 2008 to May 2012, fifty patients were randomised to operative
      stabilisation either by poking reduction and cannulated screws fixation (Group A,
      28) or by plates fixation using a sinus tarsi approach (Group B, 22). The two
      groups were comparable with respect to age, gender, BMI, the affected side, cause
      of injury, fracture type, time from injury to surgery and follow-up time. We
      collected data on operative time and radiation time, length of hospitalization,
      hospital costs, union time, full weight-bearing time, full physical activity time
      and complications and measured joint function using the American Orthopaedic Foot
      and Ankle surgery (AOFAS) score. The average follow-up time of Group A was 36.5+/
      9.3 months and 40.2+/-10.6 months in Group B. No significant difference between
      these two groups was found in radiation time, average length of hospitalization,
      union time, full weight-bearing time, full physical activity time and the average
      AOFAS score. However, the patients of Group B had longer operation time (38.0+/
      10.6 min vs. 66.5+/-9.4 min, P<0.05) and more hospital costs (6200+/-800 RMB vs.
      15000+/-2000 RMB, P<0.05). The average Bohler's angle and Gissane's angle
      preoperative were 10.9+/-5.3 and 141.3+/-12.1 in Group A, and became 31.2+/-5.1
      and 128.5+/-5.4 after operation. The average Bohler's angle and Gissane's angle
      preoperative in Group B were 11.7+/-4.0 and 138.8+/-16.2, respectively, and they
      became 30.9+/-5.2 and 124.6+/-6.8 after operation. Bohler's angle and Gissane's
      angle were significantly restored after surgery (P<0.05). Postoperative incision
      pain was more frequent in Group B than in Group A (P<0.05). Our results indicated
      that both cannulated screws and plates were efficient methods for intra-articular
      calcaneal fractures in older children. However, poking reduction and cannulated
      screws fixation had the advantages of a shorter operative time, fewer hospital
      costs and less incision pain.

PMID- 29182121
TI  - Primary epiphyseal and metaepiphyseal tubercular osteomyelitis in children A
      series of 8 case.
AB  - : Clinical series of primary epiphyseal and metaepiphyseal tubercular
      osteomyelitis are few. The purpose of our study was to retrospectively review the
      presentation, healing response and functional results of 8 such cases in
      children. MATERIAL AND METHODS: The patients were evaluated for pain, deformity,
      range of motion, limb length discrepancy (if any) and recurrence. Serial
      radiographs of the region were studied to see remineralization, obliteration of
      radiological lesions, status of physis and remodeling of the growth plate.
      RESULTS: The mean patient age was 7.1 years. Average follow up was 3.7 years. The
      mean duration of symptom before presentation was 2.9 months (range, 0.5-8
      months). Knee region was involved in 4, distal radius in 2, shoulder and distal
      fibula in 1 patient each. The lesions were either localized or diffuse depending
      upon physeal involvement and osseous destruction. At the last follow up, the
      involved joints were painfree and had useful range of motion. Limb length
      lengthening was seen in all knee patients. The diffuse variety resulted in
      premature physeal closure. The residual lucencies persisted for several years
      without any clinical manifestations. CONCLUSIONS: Primary epiphyseal and
      metaepiphyseal tuberculosis was relatively uncommon. The clinical outcome was
      good following curettage and multidrug antitubercular therapy. The epiphyseal and
      metaphyseal lucencies persisted for several months even after successful
      treatment. The diffuse variety lead to premature physeal closure. Limb length
      lengthening was common sequelae of tuberculosis of knee region.

PMID- 29182120
TI  - Risk factors for additional surgery after closed reduction of hip developmental
      dislocation.
AB  - PURPOSE: to evaluate the risk factors for additional surgery after closed
      reduction of hip developmental dislocation Methods : closed reduction for
      developmental hip dislocation was performed on 72 patients, with a total of 82
      hips (10 bilateral). Were included only patients with irreducible hip dislocation
      who were treated by overhead traction followed by closed reduction under general
      anaesthesia and spica casting. The mean age at the time of closed reduction was
      10 months, with 82% of dislocation diagnosed after the age of 6 months. In 28
      hips (34.1%), no additional surgical procedure was necessary, while 54 hips
      (65.9%) needed an additional surgery, consisting in Salter osteotomy in 40 hips
      (48.8%) or open hip reduction in 14 (17.1%). RESULTS: risk factors for the need
      of additional surgery were: older age at the time of reduction, male sex, high
      grade of hip dislocation (Tonnis grade 3 and 4, versus grade 1 and 2), and
      quality of hip reduction. All the patients older than 17 months at the time of
      closed reduction needed additional surgery. Bilateral hip dislocation had poorer
      Severin grading than unilateral dislocation. Poorer Kalamchi scoring was
      associated with older age and with the presence of the cephalic nucleus at the
      time of reduction. CONCLUSION: this study confirmed delayed diagnosis of hip
      dislocation leads to a more extensive treatment with poorer issue.

PMID- 29182122
TI  - Complications associated with bone lengthening of the lower limb by callotasis.
AB  - The present study aims to assess the incidence of complications related to bone
      lengthening procedures and to identify factors that may predict these
      complications. We retrospectively studied 51 lengthening procedures in 39
      patients (mean age 13 years) from 2001 to 2015. A circular external fixator was
      used in 37 procedures and a monolateral fixator in 14 procedures. Duration of
      distraction, fixator's time, days of treatment, lengthening percentage, bone
      healing index, distraction regenerate length, distraction index, risk factors and
      complications were evaluated. The mean follow-up was 5 years. Complications
      occurred in 84 % of the procedures. Duration of distraction, fixator's time, days
      of treatment and distraction regenerate length were predictors of complications.
      Close follow-up is necessary during distraction and healing period and after
      fixator removal.

PMID- 29182123
TI  - Angular deformity development after the distal tibial physeal fractures.
AB  - : Several clinical and radiological factors can be prognostic in the development
      of angular deformity following physeal injuries of the distal tibia. One of the
      radiological parameters, premature physeal closure (PPC), can be detected during
      postoperative follow-ups. Aim of our study was to identify the prognostic factors
      in development of angular deformity and its relationship with PPC. One hundred
      and four patients treated due to physeal injuries of the distal tibia were
      included in our study. Patients were divided into three groups based on Salter
      Harris (SH) classification. The intergroup relationships between sex, age, the
      amount of energy sustained during injury, premature physeal closure, the amount
      of residual gap, and deformity were analyzed. Angular deformity developed in 25%
      (3/12) of SH Type 2, in 60% (9/15) of Type 3 and 30% (3/10) of Type 4 patients
      with PPC. A residual displacement of more than 2 mm, age and premature physeal
      closure were specified as significant risk factors for development of angular
      deformity. 2 mm limit for residual displacement and findings of premature physeal
      closure in the radiological evaluations during follow-ups are prognostic factors
      in avoiding malalignment of the distal tibia. LEVEL OF EVIDENCE: Level 3.

PMID- 29182124
TI  - Hip preservation surgery for adolescents and young adults with Post-Perthes
      Sequelae.
AB  - BACKGROUND: Impingement ensures a narrow arc of pathologic loading in adolescent
      hips with sequelae of Perthes Disease. Proper surgical interference when the hip
      is still in the pre-arthritic stage restores function and protects the young hip
      from early degenerative changes. METHODS: Osteochondroplasty at the femoral head
      neck junction and relative lengthening of the femoral neck by distal transfer of
      the greater trochanter was performed for 12 adolescents with combined intra
      articular/extra-articular impingement due to sequelae of Perthes disease in terms
      of coxa magna, coxa plana, coxa brevis, with an overriding greater trochanter.
      The safe surgical hip dislocation approach was performed in all cases. Patients
      were followed for an average of 24 months. RESULTS: The Harris hip scores
      improved from an average of 58 preoperatively (range 50 to 69) to 94
      postoperatively (range 91 to 97) at latest follow up. The range of hip flexion
      improved from a preoperative value of 84.2 degrees  (range, 60 to 105 degrees )
      to value of 120.8 degrees  (range, 95 to 130 degrees ). Changes in hip flexion
      averaged 28.6 degrees  (range, 15 to 45 degrees ). Mean internal rotation
      increased to 26 degrees  +/- 12 degrees , and abduction to 38 degrees  +/- 11
      degrees . Alpha angle improved to 40 degrees  +/- 8 degrees . The mean of center
      trochanteric distance improved from an average of -18 mm to -1 mm. No
      osteonecrosis or chondrolysis was noted up to the time of the latest follow up.
      CONCLUSION: Elimination of narrow arc of pathologic loading due to impingement is
      the main advantage of the proposed surgical technique. Other advantages include
      increased abductor lever arm and restoration of hip joint range of motion with
      normalization of the loading conditions, and hence future development of
      degenerative arthritis and the anticipated need for a future joint replacement
      surgery could be prevented or delayed. Femoral head vascularity is well
      maintained with the proven safety of the presented surgical approach.

PMID- 29182125
TI  - Locked rigid antegrade intramedullary nailing of adolescent femoral fractures
      using a lateral trochanteric entry point.
AB  - The purpose of this study is to present our experience of treating adolescent
      femoral fractures using a locked intramedullary nail with a lateral trochanteric
      entry point. We retrospectively reviewed 15 femoral fractures in 13 adolescents
      who were treated in our unit between 2011 and 2014. Data collected included
      patient demographics, mechanism of injury, type of fracture, associated injuries,
      time to union and complications. A radiographic review was also undertaken. The
      mean time to radiological union in 14 out of the 15 fractures was 13 weeks
      (range, 10-20 weeks). One patient had a delayed union that required bone grafting
      and united finally at 30 weeks post injury. The mean difference in the neck shaft
      angle between the operated and non-operated side was 1.5 degrees (range : -10 to
      10 degrees). No patients had infection or avascular necrosis. Five nails were
      removed after the fractures had healed without complications. Locked rigid
      intramedullary nailing of adolescent femoral fractures is a safe and effective
      treatment option when the lateral aspect of the greater trochanter is used as an
      entry point.

PMID- 29182127
TI  - Lower limb equalization with percutaneus epiphysiodesis of the knee joint area.
AB  - INTRODUCTION: Epiphysiodesis has become one of the most popular methods in the
      treatment of leg length discrepancy (LLD) due to its surgical simplicity, short
      hospitalization time, and a low risk of complications. PATIENTS AND METHODS: A
      retrospective analysis was performed on 34 patients treated for LDD with
      percutaneus epiphisiodesis of the distal femur and/or the proximal tibia. The
      mean discrepancy was 2.8 cm. The outcome evaluation method was based on Kemnitz
      et al. RESULTS: Based on the Kemnitz criteria, 23 (67.6%) patients experienced
      good results, while 2 (5.9%) satisfactory and 9 (26.5%) poor results. In 47% of
      patients, swellings of the knee joint were observed in the postoperative period.
      One serious complication - varus deformity of 10 degrees in femur occurred in the
      follow-up period. CONCLUSIONS: Percutaneous epiphysiodesis is a simple method of
      the LLD correction, with a low rate of complications and applicable in cases of
      late LDD diagnosis.

PMID- 29182126
TI  - A comparison of ketamine sedation and general anaesthesia for manipulation of
      paediatric forearm fractures.
AB  - The purpose of the study was to compare the use of ketamine sedation and general
      anaesthesia for manipulation of paediatric wrist and forearm fractures. A
      retrospective analysis was performed of patients under 16 years treated at our
      centre between October 2014 and October 2015. Exclusion criteria were open
      fractures and fractures with complete displacement. Outcomes measured were
      fracture reduction, the quality of the cast, fracture redisplacement, further
      surgical intervention and use of theatre time. 66 children were manipulated over
      the study period; 31 received ketamine sedation and 35 general anaesthesia. No
      statistically significant difference was found in the rate of re-intervention
      (p=0.48), quality of reduction (p=0.39), quality of cast (p=0.14 and p=0.21), or
      redisplacement (p=0.87). Those undergoing general anaesthesia used on average 50
      minutes of theatre time and one third required an overnight admission. We
      conclude that ketamine sedation achieves comparable treatment outcomes to general
      anaesthesia whilst using fewer resources.

PMID- 29182128
TI  - Management of birth-associated subtrochanteric femur fractures.
AB  - In daily clinical practice most orthopedic surgeons suffer from doubt about
      treatment of rare injuries. The aim of this study is to enlighten the management
      of birth related femoral subtrochanteric fractures of neonates. Four birth
      related femoral subtrochanteric fractures of neonates were treated and followed
      up. Difficult caesarian breech delivery seems to be a risk factor. All patients
      were treated with Pavlik harness and union was achieved by the fourth week. None
      of the patients suffer any angulation or limb length discrepancy. Adequate
      management of this type of fractures lead to good results.

PMID- 29182129
TI  - Anatomical and functional evaluation of diaphyseal femoral fractures in children
      under 6 years old.
AB  - Objective : The aim of this study is to evaluate both the anatomical and
      functional consequences of our treatment protocol of diaphyseal femoral fractures
      in children under 6 years old Methods : We conducted a retrospective analysis of
      a series containing 50 children in Strasbourg University Hospital whom had
      traumatic diaphyseal femoral fractures and underwent conservative treatment by
      traction followed by casting with a mean follow-up period of 25 months. Results :
      All fractures healed without complications i.e. gait disorders, back pain and
      limitation of activity. Results showed a significant correlation between the
      initial varus angulation and shortening which could influence the final
      remodeling result within the first 24 months. Using the Receiver Operating
      Characteristic curve, we developed the Initial Displacement Index on Traction
      (IDIT) which is the sum of both the initial varus in degrees and the initial
      shortening in millimeters. Conclusion : The treatment by initial traction
      followed by a cast for childrens <= 6 years old gives clinical and radiological
      results comparable with those reported for immediate casting method. The
      hospitalization period is longer in the traction method but with less exposure to
      general anesthesia (GA) and risks of secondary displacements.

PMID- 29182130
TI  - Correlation of Pirani score and Foot bimalleolar angle in the treatment of
      idiopathic congenital talipes equino varus by Ponseti method in infants.
AB  - AIM: Correlation of Pirani score and Foot bimalleolar (FBM) angle in the
      treatment of idiopathic congenital talipes equino varus (CTEV) by Ponseti method
      in infants. MATERIAL AND METHODS: 35 feet with idiopathic CTEV deformity <1 year
      were prospectively treated by Ponseti method. Deformity evaluated each successive
      week of treatment by Pirani score and FBM angle. Feet were divided according to
      Pirani score in groups : one(0-2.0), two(2.5-4) and three(4.5-6). Correlation
      between mean Pirani score and mean FBM angle was evaluated every week and at
      follow up, firstly by using Pearson's and Spearman's correlation and then, after
      dividing data in groups by using ANOVA. RESULTS: Correlation between Pirani score
      and FBM angle was statistically significant(p value <0.05). CONCLUSION: Pirani
      score decreases and FBM angle increases with correction. Pirani score and FBM
      angle correlated in severity of deformity and correction achieved, thus FBM angle
      provides objective evidence of clubfoot deformity/improvement/deterioration.

PMID- 29182131
TI  - Lateral pinning versus others procedures in the treatment of supracondylar
      humerus fractures in children.
AB  - We compared results of lateral pinning procedure with crossed pinning, closed
      reduction, and open reduction in a retrospective review of 184 patients with
      displaced supracondylar humeral fractures. All patients had a minimum of 2 years
      follow-up (range 36-90 months). Patients were separated into 4 groups. Success
      was estimated by Flynn's criteria. We compared success of the lateral pinning to
      others procedures. Incidence of nerve palsy was recorded and compared. Esthetic
      effect of lateral pinning is significantly better than closed reduction
      (p=0.0007), but no significant difference was found comparing with cross pinning
      and open reduction. Elbow function was similar. Cross pinning procedure was
      followed with ulnar nerve palsy in ten patients (20.8%). There was 1 case (5%) of
      combined nerve palsy including ulnar, median and radial nerve after open
      reduction procedure. Lateral pinning is safe and effective method of therapy for
      Gartland type II and III supracondylar humeral fractures.

PMID- 29182133
TI  - Results of one-stage surgical treatment in children with Tonnis grade 4
      developmental dysplasia of the hip: is it worse when it is bilateral?
AB  - This retrospective study compared the results of one-stage surgery of unilateral
      and bilateral Tonnis grade 4 hips (high dislocation in developmental hip
      dysplasia, DDH) : 41 hips, 30 patients. Mean follow-up was 56 months. Pelvic
      radiographs were evaluated at three time points. Acetabular inclination angle
      improved significantly in both groups. Results were satisfactory (Severin classes
      I-II) in 13 hips (68.5%) (unilateral group) and 21 hips (89.5%) (bilateral
      group). Functional evaluation (McKay classification) at final follow-up revealed
      satisfactory results in 94.8% (unilateral group) and 63.6% (bilateral group). One
      stage surgery is a reliable method for treating children with unilateral or
      bilateral DDH.

PMID- 29182132
TI  - Prevention of re-fractures of both bones of the forearm in children.
AB  - PURPOSE: The aim of this study was to observe if the re-fracture rate after
      forearm both bones was decreased by protecting the forearm with a preventive
      brace for 6 months following the fracture and by ceasing all physical activities.
      METHODS: We performed a retrospective study in 75 consecutive cases of diaphyseal
      fracture of both bone of forearms, in 52 boys and 23 girls aged from 6 months to
      11 years. It concerned a first episode of fracture in 84% of cases and a re
      fracture in 17%. RESULTS: Re-fracture rate was 0% in the group where a protective
      brace was worn while it was 20% in the group without brace. CONCLUSIONS: Both the
      wearing of a protective brace and absence of sport for 6 months may decrease the
      re-fracture rate to 0%, if the patient is compliant by wearing it and by ceasing
      all physical activities.

PMID- 29182134
TI  - Titanium elastic nailing in femoral diaphyseal fractures in children of 6-14
      years age.
AB  - BACKGROUND: Traditionally conservative methods were used in managing paediatric
      femoral diaphyseal fractures. There has been a renewed interest for operative
      treatment with Titanium elastic nail system (TENS) in the age group of 6-14
      years. MATERIALS AND METHODS: This prospective study was done on 20 patients. Two
      titanium nails were used for stabilization. We followed them for maximum of two
      years. The results were evaluated using Flynn's scoring criteria. RESULTS: In our
      study we had fifteen males and five females with average age 10.35 years. Average
      time for fracture union was 9.0 weeks, full weight bearing 9.2 weeks, hospital
      stay 8.6 days and return to school at 10 weeks. The results were excellent in 14,
      good in 5 and poor in 1 patient. Most common complication was irritation at nail
      entry site. No delayed union or nonunion seen. CONCLUSION: Treatment of
      diaphyseal femoral fracture in selected pediatric patients by TENS is reasonably
      effective.

PMID- 29182135
TI  - Long-term outcome in displaced lateral humeral condyle fractures following
      internal screw fixation in children.
AB  - BACKGROUND: The aim of this study was to investigate the long-term clinical
      outcome following open reduction and internal screw fixation of displaced lateral
      condyle fractures (LCFs) of the distal humerus and compare the outcome of primary
      and secondary LCFs. METHODS: The clinical outcome in 31 children (mean age 5.8+/
      2.4 years) operated for primary or secondary LCFs was retrospectively analyzed by
      standardized clinical examination and compared using the Mayo score, Morger
      score, and Patients Satisfaction score. RESULTS: The scores did not differ
      significantly between the primary and secondary displacement groups (Mayo score:
      99.3+/-3.3 vs. 100+/-0, p=0.852; Morger score: 3.8+/-0.5 vs. 3.9+/-0.3, p=0.852;
      Patients Satisfaction score: 3.7+/-0.6 vs. 3.9+/-0.3, p=0.546). Deficits in range
      of motion and joint axis deviation were minor (< 10 degrees ) and no elbow
      instabilities were observed. CONCLUSIONS: Surgical treatment of a secondary
      displaced LCF with open reduction and internal screw fixation leads to a
      favorable long-term outcome. The long-term outcome is similar between primary and
      secondary displaced LCFs.

PMID- 29182136
TI  - Titanium elastic nailing in femoral diaphyseal fractures in children of 6-14
      years age.
AB  - PURPOSE: The purpose of this study is to report our experience of fractures in
      children riding Hoverboards. METHODS: We undertook a prospective review of all
      children attending our hospital who sustained fractures whilst riding a
      Hoverboard. Data such as patient demographics, type of fracture sustained,
      treatment received, complications and outcome were collected. RESULTS: Twelve
      children, 5 males and 7 females with ages ranging from 5.5 to 15.3 years were
      included in this study. All patients sustained upper limb fractures and the
      distal radius was the commonest fracture site (30%). Surgery was required in 6
      (50%) out of the 12 patients because the respective fractures were displaced. No
      patient had any ongoing complaints or disability at the last clinic review.  
      Conclusion : Children riding Hoverboards are predisposed to upper limb fractures
      and parents who purchase Hoverboards should be warned about this.

PMID- 29182137
TI  - Is Autologous Blood Transfusion cost effective in Adolescent Idiopathic
      Scoliosis?
AB  - The purpose of this study has been to evaluate the use of preoperative autologous
      blood donation (PABD) in the surgical treatment of adolescent idiopathic
      scoliosis (AIS). The surgical records of 37 AIS patients, Lenke type 1, were
      reviewed. Patients were classified according to whether they had entered the PABD
      (Program of Autologous Blood Donation) (25 patients) or had been rejected to join
      (12 patients non-donors). Both groups were comparable. All but one of the PADB
      patients (96%) as compared to only 2 non-donors patients (16.7%) required post
      operative transfusion. Moreover, 12 of the PABD patients (48%) did not require
      the whole stored blood. At discharge both groups had similar haemoglobin levels.
      The risk of transfusion was much higher in the PABD group. The patients in this
      group received blood even with high haemoglobin levels (>8 g/dl). Furthermore,
      31.4% of the collected blood was never used. Therefore, PABD resulted in an
      increase in procedure costs and lead to unnecessary blood transfusions.

PMID- 29182138
TI  - Dealing with sub-trochanteric fracture in a child with osteopetrosis : A case
      report.
AB  - Osteopetrosis is a rare hereditary condition which may have autosomal recessive
      or autosomal dominant inheritance. Patients tend to present most commonly with
      fractures but involvement of cranial nerves and hematopoetic system is not
      uncommon. Patients with infantile and intermediate type tend to present more
      often with problems other than orthopaedic problems. While diagnosis can be made
      on the basis of radiographs, management needs to be customized for every patient.
      Non operative and operative management both have their advantages and
      disadvantages. We are here reporting a case of sub-trochanteric fracture in an
      eight-year-old child which was managed successfully with a dynamic hip screw
      (DHS). Surgery could be performed successfully by taking precautions during
      reduction, drilling and screw placement. At the latest follow up, which was after
      one and half years of surgery, the fracture had united well and the child faced
      no limitations of activities. Thus, open reduction and fixation with DHS can be
      considered as an effective management modality for pediatric sub-trochanteric
      fractures in osteopetrosis.

PMID- 29182139
TI  - A rare case of aneurymal bone cyst of cuboid bone in a 10-year-old girl.
AB  - Aneurysmal bone cysts (ABC) are rare and they represent 1- 1.4 % of all primary
      bone tumors. ABC of cuboid bone are extremely rare, especially in children. Very
      few cases have been reported in the literature since 1967. We present a case of
      pathological fracture of cuboid bone due to an aneurysmal cyst in a 10-year-old
      girl. Surgery was performed, which included open biopsy with aspiration and
      intralesional curettage . Bone defect was then filled in by fully synthetic
      cancellous bone graft substitute consisting of pure beta-tricalcium phosphate.
      Aneurysmal cyst of cuboid bone with pathological fracture could be successfully
      treated with pure beta-tricalcium phosphate as a bone graft substitute. This
      procedure is safe with excellent outcome.Follow up to nearly four years did not
      show any recurrence.

PMID- 29182140
TI  - Popliteal artery dissection presented 12 hours after admission for a Salter III
      fracture of proximal tibia.
AB  - A 16-year-old boy sustained a salter III fracture of the upper tibia following a
      motorcycle accident. Except for well localized knee pain, the patient did not
      have any other symptom. Repeated clinical examination did not reveal any absent
      peripheral pulse. Given the state of the fracture, anatomical reduction and screw
      fixation was planned in the operating room.  Twelve hours after admission the
      patient was taken to the operating room. During the period preceding surgery he
      continued to have normal vascular clinical examinations. Further clinical
      assessment was performed in the operating room and remained to be normal. However
      after induction and upon extension of the lower limb, peripheral pulses in the
      affected side were abruptly lost. Urgent vascular exploration of the area showed
      a popliteal artery dissection necessitating a bypass graft to restore blood flow.
      We present a review of the literature alongside a case report showing how
      popliteal artery pathology in a similar context can present late and be for a
      period of time clinically undetectable.

PMID- 29182141
TI  - 360 degrees  fixation with modern instrumentations of segment separation cervical
      spine injury in a 23-month-old.
AB  - In this case report clinical and technical lessons including seven years follow
      up learned from a flexion-distraction, highly unstable cervical spine injury
      causing a complete separation of C6-7 cervical segment with tetraparesis in a 23
      month-old boy, are presented. To our knowledge this is the only documented case
      in medical literature where adult size implants (cage, plate and lateral mass
      screw-rod system) were utilized for cervical combined anterior and posterior
      internal fixation in a child under the age of two years without implant-size
      related problems. Seven years after the injury the child attends elementary
      school, can operate a wheelchair manually, and can eat and write. Computed
      tomography control showed no failure of the hardware and fusion was later
      observed in the intervertebral space of the stabilized cervical segment, however
      adjacent segment syndrome occurred without deterioration of the patient's status.
      The decision on the mode of realignment and fixation to be made in such a case
      was difficult because there is no standard procedure for infants.

PMID- 29182142
TI  - An atypical case of elbow fracture Bilateral Capitellum Humeri Fracture in a
      Teenage.
AB  - Fractures of the capitellum are rare injures of the elbow rarely seen in
      adolescents. We report a case of a 14 year-old boy who sustained a bilateral Hahn
      Steinthal type fracture of his capitelum humeri. To our knowledge, such bilateral
      injury has not been reported before in teenagers. This paper reviews the
      literature regarding the epidemiology, classification and management of this rare
      pediatric capitellar fracture.

PMID- 29182143
TI  - Joint Modeling of Mixed Plasmodium Species Infections Using a Bivariate Poisson
      Lognormal Model.
AB  - Infectious diseases often present as coinfections that may affect each other in
      positive or negative ways. Understanding the relationship between two coinfecting
      pathogens is thus important to understand the risk of infection and burden of
      disease caused by each pathogen. Although coinfections with Plasmodium falciparum
      and Plasmodium vivax are very common outside Africa, it is yet unclear whether
      infections by the two parasite species are positively associated or if infection
      by one parasite suppresses the other. In this study, we use bivariate Poisson
      lognormal models (BPLM) to estimate covariate-adjusted associations between the
      incidence of infections (as measured by the force of blood-stage infections,
      molFOI) and clinical episodes caused by both P. falciparum and P. vivax in a
      cohort of Papua New Guinean children. A BPLM permits estimation of either
      positive or negative correlation, unlike most other multivariate Poisson models.
      Our results demonstrated a moderately positive association between P. falciparum
      and P. vivax infection rates, arguing against the hypothesis that P. vivax
      infections protect against P. falciparum infections. Our findings also suggest
      that the BPLM is only useful for counts with suitably large means and
      overdispersion.

PMID- 29182144
TI  - Chikungunya Virus Disease among Travelers-United States, 2014-2016.
AB  - Chikungunya virus is a mosquito-borne alphavirus that causes an acute febrile
      illness with severe polyarthralgia. The first local transmission of chikungunya
      virus in the Western Hemisphere was reported in December 2013. In the following
      year, the virus spread throughout much of the Americas and the number of cases
      among travelers increased substantially. We reviewed the epidemiology of
      chikungunya virus disease cases reported among U.S. travelers from 2014 to 2016.
      A total of 3,941 travel-acquired cases were reported from 49 states and the
      District of Columbia; 3,616 (92%) reported travel to other countries or
      territories in the Americas; the remaining 8% reported travel to Asia, Africa, or
      the Western Pacific. The most commonly reported travel destinations were the
      Dominican Republic, Puerto Rico, and Haiti. The largest number of cases (N =
      2,780, 71%) had illness onset in 2014, followed by 2015 (N = 913, 23%) and 2016
      (N = 248, 6%). Cases occurred in every month, but 70% of case-patients had
      illness onset from April to September, the months when mosquitoes are most likely
      to be active in the continental United States. Travel-acquired chikungunya cases
      will likely continue to occur and present a risk of introduction of the virus to
      locations in the continental United States. Clinicians and public health
      officials should be educated about the recognition, diagnosis, management, and
      timely reporting of chikungunya cases.

PMID- 29182145
TI  - Experimental Zika Virus Infection of Neotropical Primates.
AB  - The establishment of a sylvatic reservoir of Zika virus (ZIKV) in the Americas is
      dependent on the susceptibility of primates of sufficient population density, the
      duration and magnitude of viremia, and their exposure to the human mosquito-borne
      transmission cycle. To assess the susceptibility of squirrel (Saimiri sp.) and
      owl monkeys (Aotus sp.) to infection, we inoculated four animals of each species
      with ZIKV from the current epidemic. Viremia in the absence of detectible disease
      was observed in both species and seroconversion occurred by day 28. ZIKV was
      detected in the spleen of three owl monkeys: one at 7 days postinoculation (dpi)
      and two at 14 dpi. This study confirms the susceptibility to ZIKV infection of
      two Neotropical primate species that live in close proximity to humans in South
      America, suggesting that they could support a widespread sylvatic ZIKV cycle
      there. Collectively, establishment of a ZIKV sylvatic transmission cycle in South
      America would imperil eradication efforts and could provide a mechanism for
      continued exposure of humans to ZIKV infection and disease.

PMID- 29182146
TI  - Immunoproteasome functions explained by divergence in cleavage specificity and
      regulation.
AB  - The immunoproteasome (iP) has been proposed to perform specialized roles in MHC
      class I antigen presentation, cytokine modulation, and T cell differentiation and
      has emerged as a promising therapeutic target for autoimmune disorders and
      cancer. However, divergence in function between the iP and the constitutive
      proteasome (cP) has been unclear. A global peptide library-based screening
      strategy revealed that the proteasomes have overlapping but distinct substrate
      specificities. Differing iP specificity alters the quantity of production of
      certain MHC I epitopes but does not appear to be preferentially suited for
      antigen presentation. Furthermore, iP specificity was found to have likely arisen
      through genetic drift from the ancestral cP. Specificity differences were
      exploited to develop isoform-selective substrates. Cellular profiling using these
      substrates revealed that divergence in regulation of the iP balances its relative
      contribution to proteasome capacity in immune cells, resulting in selective
      recovery from inhibition. These findings have implications for iP-targeted
      therapeutic development.

PMID- 29182147
TI  - Rapid re-identification of human samples using portable DNA sequencing.
AB  - DNA re-identification is used for a broad suite of applications, ranging from
      cell line authentication to forensics. However, current re-identification schemes
      suffer from high latency and limited access. Here, we describe a rapid,
      inexpensive, and portable strategy to robustly re-identify human DNA called
      'MinION sketching'. MinION sketching requires as few as 3 min of sequencing and
      60-300 random SNPs to re-identify a sample enabling near real-time applications
      of DNA re-identification. Our method capitalizes on the rapidly growing
      availability of genomic reference data for cell lines, tissues in biobanks, and
      individuals. This empowers the application of MinION sketching in research and
      clinical settings for periodic cell line and tissue authentication. Importantly,
      our method enables considerably faster and more robust cell line authentication
      relative to current practices and could help to minimize the amount of
      irreproducible research caused by mix-ups and contamination in human cell and
      tissue cultures.

PMID- 29182150
TI  - Radiation protection for surgeons and anesthetists: practices and knowledge
      before and after training.
AB  - The use of radiological activity in the operating room (OR) and a regulatory
      decrease of the eye lens dose warrant an assessment of how medical staff are
      protected from radiation. This study aims to evaluate practices and knowledge in
      radiation protection (RP) for OR doctors before and after training. A descriptive
      study of surgeons and anesthetists in a French public hospital center was
      conducted in 2016. An ad hoc questionnaire concerning occupational practices and
      knowledge about RP was distributed before and one month after RP training. Among
      103 doctors attending the training, 90 answered the questionnaire before the
      training. Results showed a lack of knowledge and good practice in RP. Most of the
      participants (86.7%) had never been trained in RP and recognized insufficient
      knowledge. Most of them (92.2%) wore a lead apron, 50.0% a thyroid-shield, 5.6%
      lead glasses, 53.3% a passive dosimeter and 17.8% an electronic dosimeter. None
      of them benefitted from collective protective equipment such as a ceiling
      suspended screen. The questionnaire following the training was completed by only
      35 doctors. A comparison before and after training results showed an improvement
      in knowledge (scores of correct responses: 5.5/16 before and 9.5/16 after
      training) but not in RP good practices (scores of correct responses: 3.2/7 before
      and 3.3/7 after training). One training session appears to be insufficient to
      improve the application of the safety rules when x-rays are used. Communication
      needs to be improved regarding RP among anesthetists and surgeons, such as
      training renewal, workstation analysis in OR related to x-ray use and
      occupational medical follow-up. Otherwise, radiological risks in OR need to be
      given better consideration, such as radio-induced cataract risk. It is necessary
      to encourage the use of dosimeters and protective equipment and to strengthen
      access to lead glasses and collective protective equipment, such as ceiling
      suspended screens. All these recommendations ensure the received dose is reduced
      to as low as is reasonably achievable.

PMID- 29182148
TI  - A new genus of horse from Pleistocene North America.
AB  - The extinct 'New World stilt-legged', or NWSL, equids constitute a perplexing
      group of Pleistocene horses endemic to North America. Their slender distal limb
      bones resemble those of Asiatic asses, such as the Persian onager. Previous
      palaeogenetic studies, however, have suggested a closer relationship to caballine
      horses than to Asiatic asses. Here, we report complete mitochondrial and partial
      nuclear genomes from NWSL equids from across their geographic range. Although
      multiple NWSL equid species have been named, our palaeogenomic and morphometric
      analyses support the idea that there was only a single species of middle to late
      Pleistocene NWSL equid, and demonstrate that it falls outside of crown group
      Equus. We therefore propose a new genus, Haringtonhippus, for the sole species H.
      francisci. Our combined genomic and phenomic approach to resolving the
      systematics of extinct megafauna will allow for an improved understanding of the
      full extent of the terminal Pleistocene extinction event.

PMID- 29182152
TI  - Decoding of finger trajectory from ECoG using deep learning.
AB  - OBJECTIVE: Conventional decoding pipeline for brain-machine interfaces (BMIs)
      consists of chained different stages of feature extraction, time-frequency
      analysis and statistical learning models. Each of these stages uses a different
      algorithm trained in a sequential manner, which makes it difficult to make the
      whole system adaptive. The goal was to create an adaptive online system with a
      single objective function and a single learning algorithm so that the whole
      system can be trained in parallel to increase the decoding performance. Here, we
      used deep neural networks consisting of convolutional neural networks (CNN) and a
      special kind of recurrent neural network (RNN) called long short term memory
      (LSTM) to address these needs. APPROACH: We used electrocorticography (ECoG) data
      collected by Kubanek et al. The task consisted of individual finger flexions upon
      a visual cue. Our model combined a hierarchical feature extractor CNN and a RNN
      that was able to process sequential data and recognize temporal dynamics in the
      neural data. CNN was used as the feature extractor and LSTM was used as the
      regression algorithm to capture the temporal dynamics of the signal. MAIN
      RESULTS: We predicted the finger trajectory using ECoG signals and compared
      results for the least angle regression (LARS), CNN-LSTM, random forest, LSTM
      model (LSTM_HC, for using hard-coded features) and a decoding pipeline consisting
      of band-pass filtering, energy extraction, feature selection and linear
      regression. The results showed that the deep learning models performed better
      than the commonly used linear model. The deep learning models not only gave
      smoother and more realistic trajectories but also learned the transition between
      movement and rest state. SIGNIFICANCE: This study demonstrated a decoding network
      for BMI that involved a convolutional and recurrent neural network model. It
      integrated the feature extraction pipeline into the convolution and pooling layer
      and used LSTM layer to capture the state transitions. The discussed network
      eliminated the need to separately train the model at each step in the decoding
      pipeline. The whole system can be jointly optimized using stochastic gradient
      descent and is capable of online learning.

PMID- 29182151
TI  - Using convolutional neural networks to estimate time-of-flight from PET detector
      waveforms.
AB  - Although there have been impressive strides in detector development for time-of
      flight positron emission tomography, most detectors still make use of simple
      signal processing methods to extract the time-of-flight information from the
      detector signals. In most cases, the timing pick-off for each waveform is
      computed using leading edge discrimination or constant fraction discrimination,
      as these were historically easily implemented with analog pulse processing
      electronics. However, now with the availability of fast waveform digitizers,
      there is opportunity to make use of more of the timing information contained in
      the coincident detector waveforms with advanced signal processing techniques.
      Here we describe the application of deep convolutional neural networks (CNNs), a
      type of machine learning, to estimate time-of-flight directly from the pair of
      digitized detector waveforms for a coincident event. One of the key features of
      this approach is the simplicity in obtaining ground-truth-labeled data needed to
      train the CNN: the true time-of-flight is determined from the difference in path
      length between the positron emission and each of the coincident detectors, which
      can be easily controlled experimentally. The experimental setup used here made
      use of two photomultiplier tube-based scintillation detectors, and a point
      source, stepped in 5 mm increments over a 15 cm range between the two detectors.
      The detector waveforms were digitized at 10 GS s-1 using a bench-top
      oscilloscope. The results shown here demonstrate that CNN-based time-of-flight
      estimation improves timing resolution by 20% compared to leading edge
      discrimination (231 ps versus 185 ps), and 23% compared to constant fraction
      discrimination (242 ps versus 185 ps). By comparing several different CNN
      architectures, we also showed that CNN depth (number of convolutional and fully
      connected layers) had the largest impact on timing resolution, while the exact
      network parameters, such as convolutional filter size and number of feature maps,
      had only a minor influence.

PMID- 29182149
TI  - Multi-scale, multi-modal analysis uncovers complex relationship at the brain
      tissue-implant neural interface: new emphasis on the biological interface.
AB  - OBJECTIVE: Implantable neural electrode devices are important tools for
      neuroscience research and have an increasing range of clinical applications.
      However, the intricacies of the biological response after implantation, and their
      ultimate impact on recording performance, remain challenging to elucidate.
      Establishing a relationship between the neurobiology and chronic recording
      performance is confounded by technical challenges related to traditional
      electrophysiological, material, and histological limitations. This can greatly
      impact the interpretations of results pertaining to device performance and tissue
      health surrounding the implant. APPROACH: In this work, electrophysiological
      activity and immunohistological analysis are compared after controlling for
      motion artifacts, quiescent neuronal activity, and material failure of devices in
      order to better understand the relationship between histology and
      electrophysiological outcomes. MAIN RESULTS: Even after carefully accounting for
      these factors, the presence of viable neurons and lack of glial scarring does not
      convey single unit recording performance. SIGNIFICANCE: To better understand the
      biological factors influencing neural activity, detailed cellular and molecular
      tissue responses were examined. Decreases in neural activity and blood
      oxygenation in the tissue surrounding the implant, shift in expression levels of
      vesicular transporter proteins and ion channels, axon and myelin injury, and
      interrupted blood flow in nearby capillaries can impact neural activity around
      implanted neural interfaces. Combined, these tissue changes highlight the need
      for more comprehensive, basic science research to elucidate the relationship
      between biology and chronic electrophysiology performance in order to advance
      neural technologies.

PMID- 29182153
TI  - Characterization of the a-Si EPID in the unity MR-linac for dosimetric
      applications.
AB  - Electronic portal imaging devices (EPIDs) are frequently used in external beam
      radiation therapy for dose verification purposes. The aim of this study was to
      investigate the dose-response characteristics of the EPID in the Unity MR-linac
      (Elekta AB, Stockholm, Sweden) relevant for dosimetric applications under
      clinical conditions. EPID images and ionization chamber (IC) measurements were
      used to study the effects of the magnetic field, the scatter generated in the MR
      housing reaching the EPID, and inhomogeneous attenuation from the MR housing.
      Dose linearity and dose rate dependencies were also determined. The magnetic
      field strength at EPID level did not exceed 10 mT, and dose linearity and dose
      rate dependencies proved to be comparable to that on a conventional linac.
      Profiles of fields, delivered with and without the magnetic field, were
      indistinguishable. The EPID center had an offset of 5.6 cm in the longitudinal
      direction, compared to the beam central axis, meaning that large fields in this
      direction will partially fall outside the detector area and not be suitable for
      verification. Beam attenuation by the MRI scanner and the table is gantry angle
      dependent, presenting a minimum attenuation of 67% relative to the 90 degrees 
      measurement. Repeatability, observed over two months, was within 0.5% (1 SD). In
      order to use the EPID for dosimetric applications in the MR-linac, challenges
      related to the EPID position, scatter from the MR housing, and the inhomogeneous,
      gantry angle-dependent attenuation of the beam will need to be solved.

PMID- 29182154
TI  - An automated, quantitative, and case-specific evaluation of deformable image
      registration in computed tomography images.
AB  - A prerequisite for adaptive dose-tracking in radiotherapy is the assessment of
      the deformable image registration (DIR) quality. In this work, various metrics
      that quantify DIR uncertainties are investigated using realistic deformation
      fields of 26 head and neck and 12 lung cancer patients. Metrics related to the
      physiologically feasibility (the Jacobian determinant, harmonic energy (HE), and
      octahedral shear strain (OSS)) and numerically robustness of the deformation (the
      inverse consistency error (ICE), transitivity error (TE), and distance
      discordance metric (DDM)) were investigated. The deformable registrations were
      performed using a B-spline transformation model. The DIR error metrics were log
      transformed and correlated (Pearson) against the log-transformed ground-truth
      error on a voxel level. Correlations of r  ?  0.5 were found for the DDM and HE.
      Given a DIR tolerance threshold of 2.0 mm and a negative predictive value of
      0.90, the DDM and HE thresholds were 0.49 mm and 0.014, respectively. In
      conclusion, the log-transformed DDM and HE can be used to identify voxels at risk
      for large DIR errors with a large negative predictive value. The HE and/or DDM
      can therefore be used to perform automated quality assurance of each CT-based DIR
      for head and neck and lung cancer patients.

PMID- 29182155
TI  - Stability and recovery of DNA origami structure with cation concentration.
AB  - We synthesized triangular and rectangular DNA origami nanostructures and
      investigated the stability and recovery of them under low cation concentration.
      Our results demonstrated that the origami nanostructures would melt when
      incubated in low cation concentration, and recover whilst kept in the
      concentration for less than 10 min. However, extending the incubation time would
      lead to irreversible melting. Our results show the possibility of application of
      DNA origami nanostructures for things such as a sensor for cation concentration
      response, etc.

PMID- 29182157
TI  - Preparation of well-distributed titania nanopillar arrays on Ti6Al4V surface by
      induction heating for enhancing osteogenic differentiation of stem cells.
AB  - Great effort has recently been devoted to the preparation of nanoscale surfaces
      on titanium-based implants to achieve clinically fast osteoinduction and
      osseointegration, which relies on the unique characteristics of the
      nanostructure. In this work, we used induction heating treatment (IHT) as a rapid
      oxidation method to fabricate a porous nanoscale oxide layer on the Ti6Al4V
      surface for better medical application. Well-distributed vertical nanopillars
      were yielded by IHT for 20-35 s on the alloy surface. The composition of the
      oxides contained rutile/anatase TiO2 and a small amount of Al2O3 between the TiO2
      grain boundaries (GBs). This technology resulted in a reduction and subsequent
      increase of surface roughness of 26-32 nm when upregulating the heating time,
      followed by the successive enhancement of the thickness, wettability and adhesion
      strength of the oxidation layer to the matrix. The surface hardness also
      distinctly rose to 554 HV in the IHT-35 s group compared with the 350 HV of bare
      Ti6Al4V. The massive small-angle GBs in the bare alloy promoted the formation of
      nanosized oxide crystallites. The grain refinement and deformation texture
      reduction further improved the mechanical properties of the matrix after IHT.
      Moreover, in vitro experiments on a mesenchymal stem cell (BMSC) culture derived
      from human bone marrow for 1-7 days indicated that the nanoscale layers did not
      cause cytotoxicity, and facilitated cell differentiation in osteoblasts by
      enhancing the gene and osteogenesis-related protein expressions after 1-3 weeks
      of culturing. The increase of the IHT time slightly advanced the BMSC
      proliferation and differentiation, especially during long-term culture. Our
      findings provide strong evidence that IHT oxidation technology is a novel
      nanosurface modification technology, which is potentially promising for further
      clinical development.

PMID- 29182156
TI  - The effects of model composition design choices on high-fidelity simulations of
      motoneuron recruitment and firing behaviors.
AB  - OBJECTIVE: Computational models often require tradeoffs, such as balancing detail
      with efficiency; yet optimal balance should incorporate sound design features
      that do not bias the results of the specific scientific question under
      investigation. The present study examines how model design choices impact
      simulation results. APPROACH: We developed a rigorously-validated high-fidelity
      computational model of the spinal motoneuron pool to study three long-standing
      model design practices which have yet to be examined for their impact on
      motoneuron recruitment, firing rate, and force simulations. The practices
      examined were the use of: (1) generic cell models to simulate different
      motoneuron types, (2) discrete property ranges for different motoneuron types,
      and (3) biological homogeneity of cell properties within motoneuron types. MAIN
      RESULTS: Our results show that each of these practices accentuates conditions of
      motoneuron recruitment based on the size principle, and minimizes conditions of
      mixed and reversed recruitment orders, which have been observed in animal and
      human recordings. Specifically, strict motoneuron orderly size recruitment
      occurs, but in a compressed range, after which mixed and reverse motoneuron
      recruitment occurs due to the overlap in electrical properties of different
      motoneuron types. Additionally, these practices underestimate the motoneuron
      firing rates and force data simulated by existing models. SIGNIFICANCE: Our
      results indicate that current modeling practices increase conditions of
      motoneuron recruitment based on the size principle, and decrease conditions of
      mixed and reversed recruitment order, which, in turn, impacts the predictions
      made by existing models on motoneuron recruitment, firing rate, and force.
      Additionally, mixed and reverse motoneuron recruitment generated higher muscle
      force than orderly size motoneuron recruitment in these simulations and
      represents one potential scheme to increase muscle efficiency. The examined model
      design practices, as well as the present results, are applicable to neuronal
      modeling throughout the nervous system.

PMID- 29182158
TI  - Structural basis for specific flagellin recognition by the NLR protein NAIP5.
AB  - The nucleotide-binding domain- and leucine-rich repeat (LRR)-containing proteins
      (NLRs) function as intracellular immune receptors to detect the presence of
      pathogen- or host-derived signals. The mechanisms of how NLRs sense their ligands
      remain elusive. Here we report the structure of a bacterial flagellin derivative
      in complex with the NLR proteins NAIP5 and NLRC4 determined by cryo-electron
      microscopy at 4.28 A resolution. The structure revealed that the flagellin
      derivative forms two parallel helices interacting with multiple domains including
      BIR1 and LRR of NAIP5. Binding to NAIP5 results in a nearly complete burial of
      the flagellin derivative, thus stabilizing the active conformation of NAIP5. The
      extreme C-terminal side of the flagellin is anchored to a sterically constrained
      binding pocket of NAIP5, which likely acts as a structural determinant for
      discrimination of different bacterial flagellins by NAIP5, a notion further
      supported by biochemical data. Taken together, our results shed light on the
      molecular mechanisms underlying NLR ligand perception.

PMID- 29182159
TI  - Epigenetic Changes of FKBP5 as a Link Connecting Genetic and Environmental Risk
      Factors with Structural and Functional Brain Changes in Major Depression.
AB  - The gene for the glucocorticoid receptor regulator FK506 binding protein 5
      (FKBP5) plays a role for risk, response to treatment, and changes in brain areas
      in major depressive disorder (MDD). Chronic stress is associated with lower
      methylation of FKBP5. Our aim was to investigate whether methylation of FKBP5
      reflected exposure to childhood adversity in MDD and controls and whether it was
      associated with structure and function of emotional processing regions. FKBP5
      intron 7 GR response element region methylation and rs1360780 allelic status were
      assessed from whole blood in 56 MDD adults and 50 controls. Using magnetic
      resonance imaging, we assessed gray matter concentration of selected areas and
      their function during valence recognition of emotional images. Childhood
      adversity was investigated using the Childhood Trauma Questionnaire. In MDD
      patients carrying the high-risk T allele of rs1360780, lower methylation of FKBP5
      was predicted by childhood adversity (F=4.95, p=0.04). In all participants, lower
      FKBP5 intron methylation levels were associated with reduced gray matter
      concentration in the inferior frontal orbital gyrus bilaterally (Wald chi
      square=11.93, pFDR<0.01) and, in MDD, with its bilaterally higher activation
      during valence recognition (Wald chi-square=5.58, p=0.02). Activation of this
      region, regardless of side, was found to be lower in MDD compared to controls
      (Wald chi-square=3.88, p=0.049) and to be inversely correlated with depression
      severity (Wald chi-square=4.65, p=0.03). Our findings support the hypothesis
      that, in genetically predisposed individuals carrying a high-risk variant of the
      gene, childhood maltreatment might induce demethylation of FKBP5. This is in turn
      associated with structural and functional changes in the inferior frontal orbital
      gyrus, a relevant area for the clinical symptoms of MDD.

PMID- 29182160
TI  - Error-related Brain Activity as a Treatment Moderator and Index of Symptom Change
      during Cognitive-Behavioral Therapy or Selective Serotonin Reuptake Inhibitors.
AB  - Increased neural error monitoring, as measured by the error-related negativity
      (ERN), is a transdiagnostic neurobiological marker of anxiety. To date, little is
      known about whether the ERN can inform the choice between first-line anxiety
      disorder treatments and whether the ERN changes following treatment completion.
      The aim of the study was to therefore assess whether the ERN is a treatment
      moderator and index of symptom change during cognitive-behavioral therapy (CBT)
      or selective serotonin reuptake inhibitors (SSRIs). Participants included adult
      volunteers (M age=25.8+/-8.5; 67% female) with principal anxiety disorders (n=60)
      or no lifetime history of Axis I psychopathology (ie, healthy controls; n=26). A
      flanker task was used to elicit the ERN at baseline and 12 weeks later, following
      either CBT or SSRIs in the patient sample. Results indicated that baseline ERN
      was a significant treatment moderator such that a more enhanced baseline ERN was
      associated with greater reduction in anxiety symptoms within individuals who
      received CBT but not SSRIs. Results also revealed that the ERN increased pre- to
      post-treatment among patients randomized to SSRIs, but remained stable among
      patients randomized to CBT and healthy controls. Together, these novel findings
      highlight that ERN may help guide treatment decisions regarding engagement in CBT
      or SSRIs, especially among individuals with an enhanced ERN. The findings also
      suggest that SSRIs have the capacity to alter individual differences in the ERN,
      providing evidence that the ERN is not entirely static in patients with anxiety
      disorders.

PMID- 29182161
TI  - Colorectal cancer in 2017: Practice-changing updates in the adjuvant and
      metastatic setting.

PMID- 29182162
TI  - Melanoma in 2017: Moving treatments earlier to move further forwards.

PMID- 29182163
TI  - Immunotherapy: Relying on quality over quantity.

PMID- 29182164
TI  - Targeting RET-driven cancers: lessons from evolving preclinical and clinical
      landscapes.
AB  - This corrects the article DOI: 10.1038/nrclinonc.2017.175.

PMID- 29182165
TI  - Me too-drugs with limited benefits - the tale of regorafenib for HCC.
AB  - This corrects the article DOI: 10.1038/nrclinonc.2017.100.

PMID- 29182166
TI  - Improving medical students' confidence with supplemental training programs: a
      medical student's view.

PMID- 29182167
TI  - Effects of nucleophilic ligands on the chain initiation efficiency of polar
      monomer polymerizations catalyzed by 2-methoxyethylaminobis(phenolate)yttrium
      complexes: a DFT study.
AB  - 2-Methoxyethylaminobis(phenolate)yttrium complexes Y(ONOOtBu)(Nu)(THF) have
      unique catalytic activity and selectivity toward the ring-opening polymerization
      (ROP) of beta-butyrolactone (BBL). Some of them also showed activity toward the
      group-transfer polymerization (GTP) of Michael-type monomers. These complexes
      with various nucleophilic ligands (Nu = CH2SiMe3, 1a; N(SiHMe2)2, 1b; OiPr, 1c)
      showed discrepant activity for ROP and GTP. The chain initiation of the ROP of
      BBL and the GTP of 2-vinylpyridine (2VP) catalyzed by these complexes is
      investigated by DFT calculations. The results indicate that, in the case of the
      ROP of BBL, less steric hindrance of the nucleophilic anionic ligand OiPr makes
      complex 1c have a higher chain initiation efficiency and thus a higher
      polymerization activity than 1a and 1b. In the case of the GTP of 2VP, the
      activity of 1a benefits from a good orbital match between the moieties of Y
      CH2SiMe3 and vinyl of 2VP. The origin of the experimentally observed inertness of
      1b has also been elucidated. These results could add to the better understanding
      of the experimentally observed activity discrepancy and shed light on the
      development of such a catalysis system.

PMID- 29182168
TI  - Unimolecular decay strongly limits the atmospheric impact of Criegee
      intermediates.
AB  - Stabilized Criegee intermediates (SCI) are reactive oxygenated species formed in
      the ozonolysis of hydrocarbons. Their chemistry could influence the oxidative
      capacity of the atmosphere by affecting the HOx and NOx cycles, or by the
      formation of low-volatility oxygenates enhancing atmospheric aerosols known to
      have an important impact on climate. The concentration of SCI in the atmosphere
      has hitherto not been determined reliably, and very little is known about their
      speciation. Here we show that the concentration of biogenic SCI is strongly
      limited by their unimolecular decay, based on extensive theory-based structure
      activity relationships (SARs) for the reaction rates for decomposition. Reaction
      with water vapor, H2O and (H2O)2 molecules, is the second most important loss
      process; SARs are also proposed for these reactions. For SCI derived from the
      most common biogenic VOCs, we find that unimolecular decay is responsible for
      just over half of the loss, with reaction with water vapor the main remaining
      loss process. Reactions with SO2, NO2, or acids have negligible impact on the
      atmospheric SCI concentration. The ambient SCI concentrations are further
      characterized by analysis of field data with speciated hydrocarbon information,
      and by implementation of the chemistry in a global chemistry model. The results
      show a highly complex SCI speciation, with an atmospheric peak SCI concentrations
      below 1 * 105 molecule cm-3, and annual average SCI concentrations less than 7 *
      103 molecule cm-3. We find that SCI have only a negligible impact on the global
      gas phase H2SO4 formation or removal of oxygenates, though some contribution
      around the equatorial belt, and in select regions, cannot be excluded.

PMID- 29182169
TI  - Molecular insights into the enhanced rate of CO2 absorption to produce
      bicarbonate in aqueous 2-amino-2-methyl-1-propanol.
AB  - 2-Amino-2-methyl-1-propanol (AMP), a sterically hindered amine, exhibits a much
      higher CO2 absorption rate relative to tertiary amine diethylethanolamine (DEEA),
      while both yield bicarbonate as a major product in aqueous solution, despite
      their similar basicity. We present molecular mechanisms underlying the
      significant difference of CO2 absorption rate based on ab initio molecular
      dynamics simulations combined with metadynamics. Our calculations predict the
      free energy barrier for base-catalyzed CO2 hydration to be lower in aqueous AMP
      compared to DEEA. Further molecular analysis suggests that the difference in free
      energy barrier is largely attributed to entropic effects associated with
      reorganization of H2O molecules adjacent to the basic N site. Stronger hydrogen
      bonding of H2O with N of DEEA than AMP, in addition to the presence of bulky
      ethyl groups, suppresses the thermal rearrangement of adjacent H2O molecules,
      thereby leading to lower stability of the transition state involving OH- creation
      and CO2 polarization. Moreover, the hindered reorganization of adjacent H2O
      molecules is found to facilitate migration of OH- (created via proton abstraction
      by DEEA) away from the N site while suppressing CO2 approach. This leads us to
      speculate that catalyzed CO2 hydration in aqueous DEEA may involve OH- migration
      through multiple hydrogen-bonded H2O molecules prior to reaction with CO2,
      whereas in aqueous AMP it seems to preferentially follow the one H2O-mediated
      mechanism. This study highlights the importance of entropic effects in
      determining both mechanisms and rates of CO2 absorption into aqueous sterically
      hindered amines.

PMID- 29182170
TI  - Layered double hydroxide and zirconium phosphate as ion exchangers for the
      removal of 'black crusts' from the surface of ancient monuments.
AB  - The chloride form of MgAl layered double hydroxide (hereafter MgAlCl) as an anion
      exchanger and the semisodic form of alpha-zirconium phosphate (hereafter ZrPNaH)
      as a cation exchanger are proposed as new cleaning agents for the removal of
      gypsum from ancient monuments. The ability of these exchangers to capture the
      calcium and sulphate ions of the gypsum powder was first investigated separately
      and then as a coupled system. MgAlCl/gypsum, ZrPNaH/gypsum and
      MgAlCl/ZrPNaH/gypsum mixtures were characterized by X-ray powder diffraction
      (XRD), field emission scanning electron microscopy (FE-SEM) and dispersive X-ray
      spectroscopy (EDX). ZrPNaH in the form of a wet paste exhibited a rapid uptake of
      calcium from gypsum powder via Na+ and H+/Ca2+ cation exchange. Gypsum powder was
      also successfully dissolved by a wet paste of MgAlCl by exploiting the Cl-/SO42-
      anion exchange reaction. However, the dehydration of the paste favoured the
      reprecipitation of a secondary gypsum that was characterized by lower
      crystallinity and smaller particle size than the pristine gypsum. The combination
      of wet MgAlCl and ZrPNaH showed a synergic effect on the dissolution of gypsum
      and partially prevented the reprecipitation of gypsum in the dry paste. Finally,
      a preliminary test of the removal of gypsum crust grown on a sandstone sample was
      performed.

PMID- 29182171
TI  - Metal-semiconductor transition of two-dimensional Mg2C monolayer induced by
      biaxial tensile strain.
AB  - Designing new two-dimensional (2D) materials with novel band topologies has
      continuously attracted intense interest in fundamental science and potential
      applications. Here, we report a unique 2D Mg2C monolayer featuring quasi-planar
      hexa-coordinate magnesium and hexa-coordinate carbon, which can be tuned from a
      metal to a semiconductor. The system has been studied using density functional
      theory, including electronic structure calculations and molecular dynamics
      simulations. In the freestanding state, the Mg2C monolayer behaves as a weak
      metal; however, by increasing the biaxial tensile strains, it can gradually be
      modulated to a gapless semimetal and then to a semiconductor. The Mg2C monolayer
      exhibits excellent dynamic and thermal stabilities and is also the global minimum
      of the 2D Mg2C system, implying the feasibility of its experimental synthesis.
      With unique band structures, the material may find applications in
      optoelectronics and electromechanics.

PMID- 29182172
TI  - Crystal phase transition of urea: what governs the reaction kinetics in molecular
      crystal phase transitions.
AB  - Because of their weak intermolecular forces and flexible molecular geometry,
      molecular crystals are renowned for their structural versatility (polymorphism)
      and the great difficulty in controlling the crystal form during synthesis.
      Despite its great importance in determining the final solid form (e.g. single
      crystal, polycrystal or amorphous), the kinetics of the crystal-to-crystal
      transformation between structures with different molecular packing has long been
      a fundamental challenge in both measurement and simulation. Here we report the
      first global potential energy surface (PES) for urea crystals obtained by
      stochastic surface walking global PES exploration. With the big data from
      thousands of crystal/amorphous forms, we, using exhaustive reaction pathway
      sampling, resolve the solid-to-solid transformation pathways between urea
      crystals from first principles. We demonstrate that the strong tendency to grow a
      large single crystal of urea can be attributed to the flat PES between major
      crystal forms that share the same hydrogen-bonding network pattern, where one
      crystal can transform to another facilely via crystal-to-crystal transition.
      Other crystal forms with distinct hydrogen-bonding network patterns can be
      excluded in crystallization due to their poor thermodynamic stability and high
      barrier of solid-to-solid transition. A general theory for predicting molecular
      solid transformation is proposed and illustrated in a simplified one-dimensional
      global PES, which is now obtainable from computational techniques established
      here.

PMID- 29182173
TI  - Mn doped porous cobalt nitride nanowires with high activity for water oxidation
      under both alkaline and neutral conditions.
AB  - We report the successful synthesis of Mn doped CoN nanowires on a carbon fiber
      cloth substrate (CFC) by a two-step strategy, which can be used as an efficient
      and stable OER electrocatalyst under both alkaline and neutral conditions.
      Benefiting from enhanced electronic interaction, high active area and electrical
      conductivity, the Mn doped CoN nanowires/CFC exhibits enhanced kinetics and
      improved cycling stability for the OER under both alkaline and neutral
      conditions. To achieve a current density of 10 mA cm-2, the Mn doped CoN
      nanowires/CFC requires an overpotential of 265 mV in alkaline solution and 285 mV
      in neutral solution.

PMID- 29182174
TI  - Controllable synthesis of titanium nitride nanotubes by coaxial electrospinning
      and their application as a durable support for oxygen reduction reaction
      electrocatalysts.
AB  - Chemical and electrochemical corrosion of a support limits the corresponding
      catalyst's performance and lifetime. In this paper, uniform TiN nanotubes are
      synthesized via coaxial-electrospinning, thermal oxidation and nitridation. The
      average diameter of nanotubes can be facilely controlled by tuning the parameters
      of coaxial electrospinning. The TiN nanotubes are modified further with Pt
      nanoparticles as Pt/TiN NT electrocatalysts. After accelerated durability tests,
      the electrochemical surface area (ECSA) and mass activity of the Pt/TiN decrease
      by only 6% and 14% respectively, while those of the Pt/C decrease by 44% and
      46.2% respectively. The enhanced activity is attributed to the strong interaction
      between the Pt nanoparticles and the TiN support, which is confirmed by the X-ray
      dispersive spectra of Pt 4f.

PMID- 29182175
TI  - Stable Fe nanomagnets encapsulated inside vertically-aligned carbon nanotubes.
AB  - Well-defined sized (5-10 nm) metallic iron nanoparticles (NPs) with body-centered
      cubic structure encapsulated inside the tip of millimeter-long vertically aligned
      carbon nanotubes (VACNTs) of uniform length have been investigated with high
      resolution transmission electron microscopy and soft X-ray spectroscopy
      techniques. Surface-sensitive and chemically-selective measurements have been
      used to evaluate the magnetic properties of the encapsulated NPs. The
      encapsulated Fe NPs display magnetic remanence up to room temperature, low
      coercivity, high chemical stability and no significant anisotropy. Our surface
      sensitive measurements combined with the specific morphology of the studied
      VACNTs allow us to pinpoint the contribution of the surface oxidized or
      hydroxidized iron catalysts present at the VACNT-substrate interface.

PMID- 29182176
TI  - A unique non-interpenetrated open-framework chalcogenide with a large cavity.
AB  - Reported here is a unique non-interpenetrated open-framework metal chalcogenide
      built on a supertetrahedral [Fe4In16S35]14- cluster. The non-interpenetrated
      feature accompanied with the relatively large-sized cluster leads to a high extra
      framework volume.

PMID- 29182177
TI  - An imidazolium-functionalized mesoporous cationic metal-organic framework for
      cooperative CO2 fixation into cyclic carbonate.
AB  - A mesoporous cationic Cr-MOF, termed FJI-C10, containing imidazolium moieties,
      Lewis acidic Cr3+ sites and free halogens is constructed for the first time by a
      topology-guided one-pot synthesis. FJI-C10 exhibits excellent performances in CO2
      adsorption (20.2 wt% at 273 K and 1 bar) and chemical fixation of CO2 into cyclic
      carbonates without the use of co-catalyst under atmospheric pressure.

PMID- 29182178
TI  - Valence orbitals and local bond dynamics around N atoms of histidine under X-ray
      irradiation.
AB  - The valence orbitals of aqueous histidine under basic, neutral and acidic
      conditions and their X-ray induced transformations have been monitored through N
      1s resonant inelastic X-ray scattering. Using density functional ab initio
      molecular dynamics simulations in the core-hole state within the Z + 1
      approximation, core-excitation-induced molecular transformations are quantified.
      Spectroscopic evidence for a highly directional X-ray-induced local N-H
      dissociation within the scattering duration is presented for acidic histidine.
      Our report demonstrates a protonation-state and chemical-environment dependent
      propensity for a molecular dissociation, which is induced by the absorption of
      high energy photons. This case study indicates that structural deformations in
      biomolecules under exposure to ionizing radiation, yielding possible alteration
      or loss of function, is highly dependent on the physiological state of the
      molecule upon irradiation.

PMID- 29182179
TI  - Functionalized deltahedral Zintl complexes Ge9R3 (R = CF3, CN, and NO2): a new
      class of superhalogens.
AB  - The assembly of atoms leads to the formation of clusters. These clusters have a
      tendency to gain their stability by forming either cations or anions. Among the
      anionic clusters, Zintl ions with multiple negative charges are a special type of
      inorganic complex generally formed from group 13, 14 and 15 elements in the
      periodic table. On the other hand, superhalogens are neutral molecules which have
      high electron affinity. Between the two different types of molecules, the former
      stabilized in the neutral state by forming a phase with alkali metal atoms, while
      the latter prefers the anionic state. Using first principle calculations, we show
      that it is also possible to design superhalogens having a Zintl core by
      functionalizing with suitable ligands like CF3, CN and NO2. The vertical
      detachment energies of these complexes indicate that they can be classified as
      superhalogens. The stability of these complexes is explained in terms of the
      jellium model. Density of states, partial density of states and natural localized
      molecular orbitals (NLMO) of these molecules lend additional information on the
      structure and bonding of these complexes.

PMID- 29182180
TI  - Predicting the frequency of extreme air quality events.
AB  - A new method for predicting the frequency of extreme air quality events is
      proposed. The method is based on knowing the number of times a pollutant is
      measured at different concentrations during a period of data collection and
      fitting this data to a Weibull-type function. Extrapolation of the function to
      higher concentrations then allows the frequency of extreme events that did not
      occur during the collection period to be predicted, albeit with an unspecified
      uncertainty. Prediction of the frequency of events over a given concentration,
      which was exceeded during the period of data collection, has also been performed
      assuming Poisson statistics. The assumption of Poisson statistics enables the
      provision of an uncertainty statement to accompany the prediction. The methods
      are trialled on a data set of daily average PM10 mass concentrations recorded at
      Marylebone Road in London between 2007 and 2016, inclusive. Using the method it
      was predicted that a daily average PM10 mass concentration of over 100 MUg m-3,
      corresponding to the highest UK Daily Air Quality Index band, should be expected
      once in just over three years and this agreed well with real observations,
      demonstrating the utility of this new technique.

PMID- 29182181
TI  - Kinetic alteration of the 6Mg(NH2)2-9LiH-LiBH4 system by co-adding YCl3 and Li3N.
AB  - The 6Mg(NH2)2-9LiH-LiBH4 composite system has a maximum reversible hydrogen
      content of 4.2 wt% and a predicted dehydrogenation temperature of about 64 
      degrees C at 1 bar of H2. However, the existence of severe kinetic barriers
      precludes the occurrence of de/re-hydrogenation processes at such a low
      temperature (H. Cao, G. Wu, Y. Zhang, Z. Xiong, J. Qiu and P. Chen, J. Mater.
      Chem. A, 2014, 2, 15816-15822). In this work, Li3N and YCl3 have been chosen as
      co-additives for this system. These additives increase the hydrogen storage
      capacity and hasten the de/re-hydrogenation kinetics: a hydrogen uptake of 4.2
      wt% of H2 was achieved in only 8 min under isothermal conditions at 180  degrees
      C and 85 bar of H2 pressure. The re-hydrogenation temperature, necessary for a
      complete absorption process, can be lowered below 90  degrees C by increasing the
      H2 pressure above 185 bar. Moreover, the results indicate that the hydrogenation
      capacity and absorption kinetics can be maintained roughly constant over several
      cycles. Low operating temperatures, together with fast absorption kinetics and
      good reversibility, make this system a promising on-board hydrogen storage
      material. The reasons for the improved de/re-hydrogenation properties are
      thoroughly investigated and discussed.

PMID- 29182182
TI  - Addition of a polyhistidine tag alters the regioselectivity of carbonyl reductase
      S1 from Candida magnoliae.
AB  - Studying enzymatic reductions of substrates with more than a single keto group is
      challenging, as the carbonyl reduction can create a vast array of regio- and
      stereoisomers. If used as reference compounds, regio- and stereopure hydroxy
      ketides could facilitate the characterization of reductases with unclear regio-
      and stereoselectivity. We have combined nonenzymatic and enzymatic reduction and
      oxidation steps to obtain all four regio- and stereoisomers of tert-butyl
      hydroxyoxohexanoates in high optical purity (enantiomeric ratio (er) of 99 : 1
      for the delta-hydroxy-beta-keto isomers; er of >97 : 3 for the beta-hydroxy-delta
      keto isomers). Furthermore, we have prepared seven of the eight possible
      regioisomers and diastereomers of gamma-methylated hydroxyoxohexanoates. These 11
      compounds allowed unraveling the complex stereoselectivity of beta,delta-diketo
      ester reductions catalyzed by carbonyl reductase S1 from Candida magnoliae (CMCR
      S1). Our analysis shows that the regio- and stereoselectivity of CMCR-S1
      catalyzed reductions is highly sensitive toward modifications at the C-terminus
      of CMCR-S1: in addition to the expected delta-hydroxy product, the variant with a
      C-terminal His-tag also led to formation of beta-hydroxy by-products with high
      optical purity.

PMID- 29182183
TI  - Dendrimer-encapsulated nanoparticle-core micelles as a modular strategy for
      particle-in-a-box-in-a-box nanostructures.
AB  - The hierarchically controlled synthesis and characterization of self-assembling
      macromolecules and particles are key to explore and exploit new nanomaterials.
      Here we present a versatile strategy for constructing particle-in-a-box-in-a-box
      systems by assembling dendrimer-encapsulated gold nanoparticles (DENs) into
      dendrimicelles. This is realized by combining positively charged PAMAM dendrimers
      with a negative-neutral block copolymer. The number of particles per
      dendrimicelle can be controlled by mixing DENs with empty PAMAM dendrimers. The
      dendrimicelles are stable in solution for months and provide improved resistance
      for the nanoparticles against degradation. The dendrimicelle strategy provides a
      flexible platform with a plethora of options for variation in the type of
      nanoparticles, dendrimers and block copolymers used, and hence is tunable for
      applications ranging from nanomedicine to catalysis.

PMID- 29182184
TI  - Raman spectroscopy studies of the terahertz vibrational modes of a DUT-8 (Ni)
      metal-organic framework.
AB  - Low-frequency lattice vibrational modes have been discussed to play a crucial
      role in the phase transformation process of flexible metal-organic frameworks
      (MOFs). Therefore, Raman spectroscopy was applied to study the lattice dynamics
      of a pillared layer DUT-8(Ni) framework (DUT - Dresden University of Technology),
      existing in rigid and flexible forms. Both the open and the close pore phases
      could be unambiguously identified by breathing mode bands at 23 cm-1 and 60 cm-1
      in the corresponding Raman spectra, showing the efficiency of the technique for
      monitoring the flexibility of MOF materials as well as the differences in the
      lattice vibrations of the two phases. Born-Oppenheimer Molecular Dynamics
      simulations showed that observed low-frequency bands indeed correspond to the
      oscillation of the breathing mode along the diagonals of the pore channels.
      Moreover, the directional character of low-frequency vibrations in the flexible
      version of DUT-8(Ni) could be visualized by the orientation dependent Raman
      spectroscopy experiment.

PMID- 29182186
TI  - Lateral sorting of chiral nanoparticles using Fano-enhanced chiral force in
      visible region.
AB  - Chiral gradient force allows a passive separation of an enantiomer since its
      direction is dependent on the handedness of its chiral entities. However, chiral
      polarisability is much weaker than electric polarisability. As a consequence, the
      non-chiral gradient force dominates over chiral force, which makes
      enantioselective sorting challenging. We present here, both numerically and
      analytically, that the chiral gradient force acting on chiral nanoparticles can
      overcome the non-chiral force when specimens are placed in a Fano-enhanced chiral
      gradient near-field using a plasmonic nanoaperture. Under circularly polarized
      light illumination, the interaction between the resonant modes of symmetric outer
      and asymmetric inner Au split-rings results in a splitting of the modal energies,
      which excites multipolar interference Fano resonances (FRs). This enables a local
      aperture between the two split-rings to possess very large optical chirality
      gradients while maintaining low gradients of electromagnetic energy density
      around the FRs from the visible region. By way of the lateral resultant force
      composed of both chiral and non-chiral gradient forces, we can accomplish a
      helicity-dependent transverse deflection of the chiral nanoparticles positioned
      above the aperture, which may offer a good platform for all-optical enantiopure
      compounds.

PMID- 29182187
TI  - New active leads for tuberculosis booster drugs by structure-based drug
      discovery.
AB  - The transcriptional repressor EthR from Mycobacterium tuberculosis, a member of
      the TetR family of prokaryotic homo-dimeric transcription factors, controls the
      expression of the mycobacterial mono-oxygenase EthA. EthA is responsible for the
      bio-activation of the second-line tuberculosis pro-drug ethionamide, and
      consequently EthR inhibitors boost drug efficacy. Here, we present a
      comprehensive in silico structure-based screening protocol that led to the
      identification of a number of novel scaffolds of EthR inhibitors in subsequent
      biophysical screening by thermal shift assay. Growth inhibition assays
      demonstrated that five of the twenty biophysical hits were capable of boosting
      ethionamide activity in vitro, with the best novel scaffold displaying an EC50 of
      34 MUM. In addition, the co-crystal structures of EthR with four new ligands at
      resolution ranging from 2.1 to 1.4 A confirm the binding and inactivation mode,
      and will enable future lead development.

PMID- 29182185
TI  - Wearable sensors: modalities, challenges, and prospects.
AB  - Wearable sensors have recently seen a large increase in both research and
      commercialization. However, success in wearable sensors has been a mix of both
      progress and setbacks. Most of commercial progress has been in smart adaptation
      of existing mechanical, electrical and optical methods of measuring the body.
      This adaptation has involved innovations in how to miniaturize sensing
      technologies, how to make them conformal and flexible, and in the development of
      companion software that increases the value of the measured data. However,
      chemical sensing modalities have experienced greater challenges in commercial
      adoption, especially for non-invasive chemical sensors. There have also been
      significant challenges in making significant fundamental improvements to existing
      mechanical, electrical, and optical sensing modalities, especially in improving
      their specificity of detection. Many of these challenges can be understood by
      appreciating the body's surface (skin) as more of an information barrier than as
      an information source. With a deeper understanding of the fundamental challenges
      faced for wearable sensors and of the state-of-the-art for wearable sensor
      technology, the roadmap becomes clearer for creating the next generation of
      innovations and breakthroughs.

PMID- 29182188
TI  - Carbon cloth supported cobalt phosphide as multifunctional catalysts for
      efficient overall water splitting and zinc-air batteries.
AB  - Excellent performance and multifunctional electrocatalysts are of great
      importance for the development of renewable energy. Here, a multifunctional
      carbon cloth supported cobalt phosphide (CoP@CC) electrocatalyst was synthesized
      via a simple electrochemical deposition followed by subsequent phosphorization.
      This self-standing CoP@CC presents superior HER performance in both acid and
      alkaline media and excellent OER activity in an alkaline environment. When
      applied as both anode and cathode catalyst to overall water splitting, CoP@CC
      only required a low cell voltage of 1.68 V to drive a current density of 10 mA cm
      2, making this catalyst a potential candidate in industrial application.
      Moreover, inspired by its satisfying ORR activity, CoP@CC was first used as the
      air-electrode in zinc-air batteries, which outputted an open-circuit potential of
      0.6 V and a power density of ~30 mW cm-2.

PMID- 29182189
TI  - A colorimetric competitive displacement assay for the evaluation of catalytic
      peptides.
AB  - An indicator displacement assay has been adapted to detect the diol products of
      the aldol reaction between 4-nitrobenzaldehyde and hydroxyacetone in crude
      reaction mixtures. This provides a rapid colorimetric method of detecting product
      formation and thus evaluating potential catalysts, which is demonstrated using
      multiple catalytic peptides.

PMID- 29182190
TI  - [Association between socioeconomic status and survival after a first episode of
      myocardial infarction].
AB  - BACKGROUND: A low socioeconomic status is associated with higher overall
      mortality rates. AIM: To assess the effect of socioeconomic inequalities on
      survival of patients hospitalized with a first myocardial infarction. MATERIAL
      AND METHODS: Analysis of hospital discharge and mortality databases of the
      Ministry of Health. Patients aged over 15 years discharged between 2002 and 2011
      with a first myocardial infarction (code I-21, ICD-10) were identified. Their
      survival was verified with the mortality registry. Survival from 0 to 28 and from
      29 to 365 days was analyzed. Socioeconomic status was determined using the type
      of health insurance, stratified as public insurance (low and medium status) and
      private insurance (high status). Prais-Winsten trend (P-W) and Cox survival
      analyses were done. RESULTS: We analyzed 59,557 patients (69% males). Sixty three
      percent were of low socioeconomic status, 19% medium and 18% high. Between 2002
      and 2011 the increase in survival was higher among patients of low socioeconomic
      status, mainly in women (P-W coefficients 0.58:0.31-0.86 in men and 1.12:0.84
      1.41 in women for 0-28 days survival and 0.24:0.09-0.39 in men and 0.48:0.37-0.60
      in women for 29-365 days survival, respectively). However, age and year of
      hospitalization adjusted analysis showed a higher mortality risk among patients
      of low socioeconomic status at 0-28 days (HR 1.67:1.53-1.83 for men and 1.49:1.34
      1.66 for women) and at 29-365 days (HR 2.30:1.75-2.71 for men and 1.90:1.56-1.85
      for women). CONCLUSIONS: Survival after a myocardial infarction improved in the
      last decade especially in patients of low socioeconomic status. However, subjects
      of this stratum continue to have a higher mortality.

PMID- 29182191
TI  - [Association of active commuting with obesity: findings from the Chilean National
      Health Survey 2009-2010].
AB  - BACKGROUND: Active commuting is associated with a lower risk for obesity in
      developed countries. AIM: To investigate the association between active commuting
      and obesity risk in Chile. MATERIAL AND METHODS: Active commuting was measured
      using the Global Physical Activity Questionnaire (GPAQ v2) in 5,293 participants
      from the Chilean National Health Survey 2009-2010. Body mass index (BMI) and
      waist circumference (WC) were the study outcomes. The association between active
      commuting and obesity was investigated using linear and logistic regression
      analysis. RESULTS: Thirty four percent of responders [95% confidence intervals
      (CI): 32.6-35.1] were passive commuters. Active commuters had a lower BMI and WC
      than their passive counterparts. Thirty minutes increment in active commuting
      were associated with a -0.20 kg.m-2 lower BMI [95% CI: -0.33 to -0.07, p < 0.01]
      and a -076 cm lower WC [95% CI: -1.08 to -0.43, p < 0.01]. The odds of having a
      BMI > 25 kg.m-2 was 0.93 [95% CI: 0.88 to 0.98, p = 0.01] per every 30 minutes'
      increment in active commuting, whereas the odds for central obesity was 0.87 [95%
      CI: 0.82 to 0.92, p < 0.01]. CONCLUSIONS: Active commuting is associated with a
      lower adiposity and lower risk for obesity in Chilean adults.

PMID- 29182192
TI  - [Effects of high-intensity interval training and nutritional education in
      patients with type 2 diabetes].
AB  - BACKGROUND: High-intensity interval training (HIIT) improves cardiometabolic
      markers, but its effects on the quality of life of patients with type 2 diabetes
      (T2D) is not well known. AIM: To determine the effects of a 12-week HIIT exercise
      program on cardiometabolic and quality of life variables of T2D patients.
      MATERIAL AND METHODS: Nine T2D women were assigned to a HIIT + nutritional
      education (GE) and 10, to a nutritional education alone group (GC). At baseline
      and after each intervention, anthropometric and body composition parameters using
      bio-impedance were assessed, and a blood sample was obtained to measure serum
      lipid levels, blood glucose and glycated hemoglobin. Quality of life was assessed
      using the SF-12 questionnaire adapted for the Chilean population. RESULTS: There
      were no significant changes on the lipid profile variables in the GE group,
      although HDL cholesterol was increased significantly (p < 0.05) in the GC group.
      Total fat mass was decreased in the GE group from 43.5 +/- 1.5 to 41.9 +/- 1.5%,
      p < 0.01. Fasting glucose and glycated hemoglobin decreased in the GE group.
      There was a significant correlation between the decrease in total fat mass and
      that of glycated hemoglobin. There were significant increases in quality of life
      parameters; physical function, physical role, pain, general health, vitality,
      emotional role, mental health, and social function in the GE but not in the GC
      group. CONCLUSIONS: A 12-week program of HIIT plus nutritional education improves
      cardiometabolic and quality of life parameters on type 2 diabetics.

PMID- 29182193
TI  - [Microarrays in 236 patients with neurodevelopmental disorders and congenital
      abnormalities].
AB  - BACKGROUND: In 20% of neurodevelopmental disorders (NDD) and congenital
      abnormalities (CA) the cause would be a genomic imbalance detectable only by
      chromosomal microarrays (CMA). AIM: To analyze the results of CMA performed at
      the INTA Laboratory of Molecular Cytogenetics, during a period of four years in
      patients with NDD or CA. MATERIAL AND METHODS: Retrospective study that included
      all CMA reports of Chilean patients. Age, sex, clinical diagnosis and origin were
      analyzed, as well as the characteristics of the finding. The percentage of cases
      diagnosed by CMA was calculated considering all patients with pathogenic (PV) or
      probably pathogenic variants (VLP). Finally, we studied the association between
      patients' characteristics and a positive CMA outcome. RESULTS: A total of 236
      reports were analyzed. The median age was 5.41 (range 2.25-9.33) years, and 59%
      were men. Ninety chromosomal imbalances were found, which corresponded mainly to
      deletions (53.3%), with a median size of 1.662 (range 0.553-6.673) Megabases. The
      diagnostic rate of CMA in Chilean patients from all over the country was 19.2%.
      There was a close relationship between the patient's sex and the detection of
      VLP/VP (p = 0.034). CONCLUSIONS: Our diagnostic rate and the association between
      female sex and a higher percentage of diagnosed cases are concordant with other
      international studies. Therefore, CMA is a valid diagnostic tool in the Chilean
      population.

PMID- 29182195
TI  - [Assessment of a Chilean Spanish version of the Patient Assessment of Chronic
      Illness Care Questionnaire].
AB  - BACKGROUND: The Patient Assessment of Chronic Illness Care (PACIC) questionnaire
      is a widely used instrument to assess chronic disease care from a patient's
      perspective. AIM: To adapt the PACIC questionnaire to Chilean Spanish and to
      evaluate the psychometric properties of the translation. MATERIAL AND METHODS:
      Descriptive, cross-sectional design with exploratory and confirmatory factor
      analysis. The PACIC questionnaire was applied, throughout an external client, to
      200 users who received health care at the cardiovascular program in a Family
      Health Center in Concepcion, Chile. RESULTS: The confirmatory factor analysis did
      not show a good adjustment with the proposed structure in the original
      instrument. An exploratory factor analysis revealed five factors explaining 58%
      of total data variability. The distribution of the factor-items of the original
      questionnaire underwent some modifications, which are explained when analyzing
      the theoretical construct. A good reliability of the global scale was obtained
      (Cronbach's alpha 0.886). CONCLUSIONS: The PACIC questionnaire, Chilean version
      does not replicate the proposed structure of the original questionnaire.
      Therefore, further research about its validity, incorporating a higher number or
      diversity of participants is recommended.

PMID- 29182194
TI  - [Performance of an abbreviated mini mental examination to detect dementia in
      older people].
AB  - BACKGROUND: The usefulness of the abbreviated Mini-Mental State Examination
      included in the Chilean Functional assessment of elderly people (MM-SE-EFAM) to
      detect Dementia has not been determined. AIM: To assess the performance of the
      MMSE-EFAM to detect dementia. MATERIAL AND METHODS: We studied a non
      probabilistic sample of subjects older than 65 years who had been assessed by the
      MMSE-EFAM in a Chilean primary care center during a period of 6 months. Patients
      underwent clinical evaluation by a neurologist blinded to MMSE-EFAM score, to
      establish the diagnosis of dementia using DSM-IV-TR criteria. Besides, the full
      Mini-Mental State Examination (MMSE) was applied. RESULTS: The clinical diagnosis
      of Dementia was established in 13 of the 54 peoples evaluated. MMSE-EFAM had a
      sensitivity of 30.8% (95% confidence intervals (CI); 9-61.4) and a specificity of
      90.2% (95% CI; 76.9%-97.3%), while MMSE had a sensitivity of 84.6% (95% CI; 54.6
      98.1) and a specificity of 58.5% (95% CI; 42.1-73.7). In a receiver operating
      characteristic (ROC) curve analysis, the areas under the curve (AUC) were 0.77
      (95% CI; 0.61-0.93) and 0.82 (95% CI; 0.70-0.95) for MMSE-EFAM and MMSE,
      respectively. Socio-demographic variables did not influence test performance in
      both cases. CONCLUSIONS: MMSE-EFAM has a low sensitivity to detect patients with
      Dementia and it is not an effective screening tool. These results are in
      agreement with the evidence and international guidelines that do not support the
      use of cognitive screening tools to detect dementia in the older general
      population.

PMID- 29182196
TI  - [Attributes and features of a community health model from the perspective of
      practitioners].
AB  - BACKGROUND: The Family and Community Health Model is based on three essential
      principles: user-centered care, comprehensive care and continuity of care. AIM:
      To describe the attributes and characteristics of the guiding principles of the
      Family and Community Health Model (FHM) from the perspective of primary care
      experts. MATERIAL AND METHODS: This was a qualitative study. An electronic Delphi
      was conducted with 29 national experts on primary care. RESULTS: The experts
      agree that user centered care must be based on a psycho-social model integrating
      the multiple factors that influence health problems. It also must integrate
      patients' individual features, family and environmental issues. The proposed
      actions promote shared decision making. To promote integral care, anticipatory
      guidelines should be expanded and health care of patients with chronic conditions
      should be improved. Continuity of care should be promoted increasing working
      hours of medical centers and easing access to integrated electronic medical
      records, thereby generating efficient links between the different care levels.
      CONCLUSIONS: The results of the study can guide the clinical and administrative
      management of health teams, allowing the strengthening of primary health care
      according to the local realities.

PMID- 29182197
TI  - [Nurses' workload in hemodialysis units].
AB  - BACKGROUND: Knowing nurses' workload in hemodialysis units allows a better
      organization of human resources. AIM: To determine nurses' workload according to
      dependence and risk profiles of patients undergoing chronic hemodialysis.
      MATERIAL AND METHODS: One hundred fifty one patients from five hemodialysis units
      were selected and categorized in terms of dependence and risk using the
      instrument "Care according to dependence and risk in hemodialysis (CUDYR-DIAL).
      Nurses' activities for direct and indirect care and the time taken to complete
      those activities were measured. RESULTS: Per patient, nurses used 36.5 +/-10.7
      min for direct and 23.6 min for indirect care. The time required for direct care
      of patients at high risk with partial dependence and at high risk and partial
      self-sufficiency was 41.2 and 40.3 minutes respectively. CONCLUSIONS: During a
      dialysis session, nurses occupy 60% of their time providing direct care, mainly
      directed to patients categorized as being of high risk-partial dependence and
      high risk-partial self-sufficiency.

PMID- 29182198
TI  - [Abnormal expansion of C9orf72 gene in familial frontotemporal dementia].
AB  - Frontotemporal Dementia (FTD) and Motor Neuron Disease (MND) may share similar
      pathogenic mechanisms. An abnormal hexanucleotide expansion in C9orf72 gene is
      the most common genetic abnormality of these conditions and explains their
      concurrence in the same family. We report a 77-year-old female presenting with
      non-fluent aphasia leading to mutism and a mild Parkinsonism. A magnetic
      resonance imaging showed a severe atrophy of frontal and temporal lobes. Several
      family members of the patient suffered of atypical Parkinsonism, lateral
      amyotrophic sclerosis and dementia. We identified an abnormal hexanucleotide
      expansion in the C9orf72 gene in the proband. To the extent of our knowledge,
      this is the first time that this diagnosis is confirmed in our country. The
      knowledge of the genetic basis of neuro degenerative disorders improves diagnosis
      and opens expectatives for future treatments of these disabling conditions.

PMID- 29182199
TI  - [An analysis of essential health research in Chile].
AB  - Essential research studies of health problems affecting the majority of the
      population, aiming at actions that are feasible to be taken, efficiently and
      effectively implementing there and seeking solutions to unsolved problems. This
      is a complex process, which requires long lasting participation and coordinated
      interaction between different relevant sectors, namely the academic world, health
      policymakers and health-related industries. An analysis of essential health
      research in Chile is presented, considering factors such as shared efforts
      between the academic and health care sectors and the role of the Ministry of
      Health in research promotion. The following suggestions are made: 1) The Ministry
      of Health, along with universities, should stimulate, guide and monitor research
      activities that enrich and update the work on priority health issues; 2) To
      strengthen the capacity building of clinical or public health specialists by
      training them in applied research within medical centers, mainly teaching
      centers; 3) To assess the performance of National Fund for Health Research and
      Development (FONIS) and, if necessary, increase its resources to stimulate
      applied research in health; 4) To establish priorities for essential research,
      more specific than those proposed in 2010; 5) To reactivate the National Council
      for Health Research (CONIS) as an autonomous entity that coordinates applied
      research within the Ministry of Health.

PMID- 29182200
TI  - [Epigenetics of polycystic ovary syndrome].
AB  - Polycystic ovarian syndrome (PCOS) is an endocrine and metabolic dysfunction,
      highly prevalent in women in their reproductive years. Hyperandrogenism, oligo
      ovulation, polycystic ovarian morphology are the main features of this syndrome.
      PCOS is a genetic disorder with a multifactorial etiology and has a strong link
      with environmental components. It is frequently associated with obesity and
      insulin resistance. Recently, epigenetic mechanisms have been involved in the
      pathogenesis of PCOS. Several studies showed that methylation in DNA and miRNAs
      is altered in women with PCOS in blood, serum, adipose tissue, granulose cells
      and theca. This evidence indicates that women with PCOS have a different
      epigenetic regulation, which might be triggered by an adverse intrauterine
      environment or by postnatal environmental elements such as diet and or obesity.

PMID- 29182201
TI  - [Indian 'humor' in medical knowledge during the 16th and 17th centuries].
AB  - During the first Modern Era (15th-17th c.), bodily health and expressions of
      physiognomy were explained under the doctrine of humors. This doctrine -based on
      Corpus Hipocraticum-established a close relation between humors (blood, yellow
      bile, phlegm, and black bile), qualities (dry, moist, warm, and cold) and the
      elements (water, air, earth, and fire). One of these humors -black bile-,
      commonly a hallmark of the melancholic temperament, was associated to the
      complexion and nature of American Indians. This accusation was legitimized by the
      empirical examination of the physiognomy of a subject that was melancholic, sad
      and pusillanimous. In this article, we describe, based on the analysis of
      colonial texts (16th-17th c.), how the essential premises of the humor theory
      were transferred to the New World and in particular and how the Indian complexion
      was defined through the examination of subjects plagued by black humor and
      phlegm. With this, we determine the way these individuals -referred as 'Indians'-
      were inscribed in medical knowledge, during the global spread of the Hippocratic
      Galenic postulates.

PMID- 29182202
TI  - [The educational context to train health care professionals. A qualitative
      approach].
AB  - BACKGROUND: There are differences in the educational context in Health Sciences,
      between clinical and non-clinical teachers. Therefore, the didactic and reflexive
      peculiarities of both educational scenarios should be analyzed. AIM: To describe
      the conditions of the educational context in Health Sciences for the practice of
      the teaching role in a Chilean university. MATERIAL AND METHODS: Qualitative
      study, performed according to Grounded Theory of Strauss and Corbin. Thirty one
      teachers from six health sciences programs were selected according to Patton's
      maximum variation criterion and contacted personally, after an informed consent
      process. Semi-structured interviews and focus group were performed, analyzed by
      open coding, using the constant comparison method, with the Atlas-ti 7.5.2
      software. RESULTS: Six conditions of the educational context that can support the
      teaching role in these careers emerged. Namely, a clinical field suited for
      patient attention and teaching, classrooms designed for the new educational
      models, number of students in the classrooms and clinical settings, insertion
      programs for teachers' training, teachers' coordination and economic resources of
      the program. CONCLUSIONS: Health Sciences programs are developed in a complex
      educational context, having to articulate diverse elements to train
      professionals. Therefore, it is fundamental to understand the conditions of the
      educational context that can favor the practice of the teaching role, thus
      generating improvements in teaching-learning process.

PMID- 29182203
TI  - [Self-directed learning and academic background of 2010 to 2014 cohorts of
      medical students].
AB  - BACKGROUND: The widespread growth of higher education is increasing the
      heterogeneity of university students in terms of socioeconomic characteristics,
      academic story and cultural background. Medical schools are not an exception of
      this phenomenon. AIM: To compare the academic background and self-directed
      learning behavior of students who entered to a public medial school between 2010
      and 2014. MATERIAL AND METHODS: A non-probabilistic sample of 527 medical
      students aged between 17 and 29 years (60% men), was studied. Their academic
      information was collected from the University data base; they answered the Self
      directed learning readiness scale of Fisher. RESULTS: Students from the 2014
      cohort had higher high school grades than their counterparts. The scores in
      mathematics of the Scholarship Aptitude Test (SAT) were higher in the cohorts of
      2010 and 2011. Those of the sciences test were superior in the 2013 cohort. The
      2014 cohort had the lower general score of self-directed learning behaviors.
      CONCLUSIONS: The lower SAT and self-directed learning scores of the students
      entering medical school in 2014, indicate the progressive increase in the
      heterogeneity of Medical students.

PMID- 29182204
TI  - [Long QT syndrome and polymorphic ventricular tachycardia due to hypopituitarism.
      Report of one case].
AB  - Symptoms of hypopituitarism are usually chronic and nonspecific, but rarely the
      disease can have acute and life threatening manifestations. We report a 53 years
      old female with a pituitary adenoma that was admitted to our hospital because of
      syncope. The electrocardiogram showed sinus bradycardia with a prolonged QT
      interval. Frequent runs of non-sustained polymorphic ventricular tachycardia were
      noted on telemetry. The patient had a history of severe acute headaches in the
      previous days and laboratory tests revealed severe secondary hypothyroidism,
      adrenal insufficiency and a decrease in pituitary hormones. A magnetic resonance
      imaging of the head showed changes in the size and contrast enhancement of the
      adenoma. A diagnosis of hypopituitarism secondary to pituitary apoplexy was made
      and treatment with hydrocortisone and, subsequently, levothyroxine was started.
      Hormonal disorders such as hypothyroidism, adrenal insufficiency or
      hypopituitarism should be considered as unusual causes for reversible
      cardiomyopathy, long QT syndrome and ventricular arrhythmias.

PMID- 29182205
TI  - [Large B-cell lymphoma coexisting with Castleman's disease. Report of one case].
AB  - We report a 73-year-old female patient with Castleman's disease coexistent with
      large B cell type non-Hodgkin's lymphoma in a right axillary lymphadenopathy. An
      excisional biopsy was performed: microscopically, the lymph node revealed the
      presence of numerous plasma cells and small lymphoid cells characteristic of
      Castleman's disease. An analysis of another portion of the specimen revealed
      lymphoid cells with large abnormal nuclei gathered locally that were CDD 79+, CD
      38+ and MUM-1+ as well as positive for Kaposi sarcoma-associated herpesvirus and
      negative for Epstein Barr virus encoded RNA-1 (EBER).

PMID- 29182206
TI  - [McKrittick-Wheelock syndrome. Report of one case].
AB  - McKittrick-Wheelock syndrome is caused by chronic water and electrolyte
      hypersecretion from an intestinal tumor, usually a villous adenoma, located in
      the rectum or sigmoid. Patients often have dehydration, hypovolemic shock and
      kidney failure associated with hypokalemia, hyponatremia, hypochloremia and
      metabolic acidosis. We report a 62-year-old male, suffering chronic diarrhea for
      eight years who was admitted after a syncope. He had severe hypokalemia,
      hyponatremia, metabolic acidosis, hypovolemia and acute renal failure. After his
      metabolic disorders were corrected, a colonoscopy showed a large rectosigmoid
      tumor with the characteristics of a villous adenoma. During the follow up after
      the complete tumor resection, the patient has remained asymptomatic.

PMID- 29182207
TI  - [Considerations in the management of ruptured mycotic aortic aneurysm secondary
      to salmonella aortitis].

PMID- 29182209
TI  - ?

PMID- 29182208
TI  - [The importance of reporting validity and reliability in measuring instruments:
      Comments to Arancibia et al].

PMID- 29182210
TI  - The role of point-of-care ultrasound in intra-abdominal hypertension management.
AB  - BACKGROUND: Intra-abdominal hypertension is a common complication in critically
      ill patients. Recently the Abdominal Compartment Society (WSACS) developed a
      medical management algorithm with a stepwise approach according to the evolution
      of the intra-abdominal pressure and aiming to keep IAP <= 15 mm Hg. With the
      increased use of ultrasound as a bedside modality in both emergency and critical
      care patients, we hypothesized that ultrasound could be used as an adjuvant point
      of-care tool during IAH management. This may be particularly relevant to the
      first and second basic stages of the algorithm. The objective of this paper is to
      test the use of POCUS as an adjuvant tool in the management of patients with
      IAH/ACS. METHODS: Seventy-three consecutive adult critically ill patients
      admitted to the surgical intensive care unit (ICU) of a single urban institution
      with risk factor for IAH/ACS were enrolled. Those who met the inclusion criteria
      were allocated to undergo POCUS as an adjuvant tool in their IAH/ACS management.
      RESULTS: A total of 50 patients met the inclusion criteria and were included in
      the study. The mean age of study participants was 55 +/- 22.6 years, 58% were
      men, and the most frequent admission diagnosis was post-operative care following
      abdominal intervention. All admitted patients presented with a degree of IAH
      during their ICU stay. Following step 1 of the WSACS IAH medical management
      algorithm, ultrasound was used for NGT placement, confirmation of correct
      positioning, and evaluation of stomach contents. Ultrasound was comparable to
      abdominal X-ray, but shown to be superior in determining the gastric content
      (fluid vs. solid). Furthermore, POCUS allowed faster determination of correct NGT
      positioning in the stomach (antrum), avoiding bedside radiation exposure.
      Ultrasound also proved useful in: 1) evaluation of bowel activity; 2)
      identification of large bowel contents; 3) identification of patients that would
      benefit from bowel evacuation (enema) as an adjuvant to lower IAP; 4) and in the
      diagnosis of moderate to large amounts of free intra-abdominal fluid. CONCLUSION:
      POCUS is a powerful systematic ultrasound technique that can be used as an
      adjuvant in intra-abdominal hypertension management. It has the potential to be
      used in both diagnosis and treatment during the course of IAH.

PMID- 29182211
TI  - Assessment of hypovolaemia in the critically ill.
AB  - Assessment of the intravascular volume status of patients is one of the most
      challenging tasks for the intensive care clinician. It is also one of the most
      important skills in intensive care management as both hypervolaemia and
      hypovolaemia lead to increased morbidity and mortality. The assessment of
      hypovolaemic patients is aided by several clinical signs, laboratory
      investigations, and a multitude of haemodynamic monitoring systems. This review
      aims to outline the definitions, pathophysiology, and various assessment
      techniques (both old and new) employed by intensivists on the critically ill
      patient.

PMID- 29182212
TI  - A Randomised Controlled Trial of a Universal Bonding Agent at Three Years: Self
      Etch vs Total Etch.
AB  - General dental practice is increasingly being recognised as the ideal situation
      for the conduct of clinical trials into the longevity of restorations. The aim of
      this study was to investigate the survival of 64 nanofilled resin composite
      (Filtek Supreme XTE) restorations placed principally in loadbearing cavities
      using a Universal dentine bonding agent (Scotchbond Universal), in five UK dental
      practices by members of the UK-based practice-based research group, the PREP
      Panel. A split mouth design was used, comprising patients who required two
      restorations, with one of the restorations receiving a total etch approach using
      phosphoric acid and the other being placed using a self-etch approach. The
      results indicated good performance of the restorations examined, with no
      difference, in terms of marginal characteristics, between the restorations which
      received total etching and those which did not.

PMID- 29182213
TI  - The Effect of Core and Veneering Design on the Optical Properties of Polyether
      Ether Ketone.
AB  - This study aimed to evaluate the effect of core shade and core and veneering
      thickness on color parameters and translucency of polyether ether ketone (PEEK).
      Sixty PEEK discs (0.5 and 1 mm in thickness) with white and dentine shades were
      veneered with A2 shade indirect composite resin with 0.5, 1 and 1.5 mm thickness
      (n=5). Cores without the veneering material served as controls for translucency
      evaluation. Color parameters were measured by a spectroradiometer. Color
      difference (DeltaE00) and translucency parameters (TP) were computed. Data were
      analyzed using one-way ANOVA and Tukey's test (for veneering thickness) and
      independent t-test (for core shade and thickness) via SPSS 20.0 (p?0.05).
      Regarding the veneering thickness, white cores of 0.5 mm thickness showed
      significant differences in all color parameters. In white cores of 1 mm thickness
      and dentine cores of 0.5 and 1 mm thickness, there were statistically significant
      differences only in L*, a* and h*. The mean TP was significantly higher in all
      white cores of 1 mm thickness than dentine cores of 1 mm. Considering
      DeltaE00=3.7 as clinically unacceptable, only three groups had higher mean
      DeltaE00 values. Core shade, core thickness, and the veneering thickness affected
      the color and translucency of PEEK restorations.

PMID- 29182214
TI  - An Investigation into the Trueness and Precision of Copy Denture Templates
      Produced by Rapid Prototyping and Conventional Means.
AB  - OBJECTIVE: To assess the trueness and precision of copy denture templates
      produced using traditional methods and 3D printing. MATERIAL AND METHODS: Six
      copies of a denture were made using: 1. Conventional technique with silicone
      putty in an impression tray (CT). 2. Conventional technique with no impression
      tray (CNT). 3. 3D scanning and printing (3D). Scan trueness and precision was
      investigated by scanning a denture six times and comparing five scans to the
      sixth. Then the scans of the six CT, CNT and 3D dentures were compared by
      aligning, in turn, the copies of each denture to the scanned original. Outcome
      measures were the mean surface-to-surface distance, standard deviation of that
      distance and the maximum distance. Student's unpaired t-tests with Bonferroni
      correction were used to analyse the results. RESULTS: The repeated scans of the
      original denture showed a scan trueness of 0.013mm (SD 0.002) and precision of
      0.013mm (SD 0.002). Trueness: CT templates, 0.168mm (0.047), CNT templates
      0.195mm (0.034) and 3D 0.103mm (0.021). Precision: CT templates 0.158mm (0.037),
      CNT 0.233mm (0.073), 3D 0.090mm (0.017). For each outcome measure the 3D
      templates demonstrated an improvement which was statistically significant
      (p?0.05). CONCLUSIONS: 3D printed copy denture templates reproduced the original
      with greater trueness and precision than conventional techniques.

PMID- 29182215
TI  - A Measurement Protocol for the Marginal and Internal Fit of All-Ceramic Crowns.
AB  - AIMS: To evaluate in vitro the influence of firing on marginal and internal fit
      of all-ceramic milled and pressed lithium-disilicate crowns. MATERIALS AND
      METHODS: One Standardized model with 1.6mm occlusal and 1.4mm axial reduction was
      used to fabricate 64 crowns. Using a factorial design, eight groups of lithium
      disilicate ceramics (n=8) using P=press, C=CAD/CAM, M=monolithic, O=coping,
      V=veneered, R=as produced: PMR, PMG, POR, PVG, CMR, CMG, COR, CVG. Crowns were
      produced and cemented on stone dies, then embedded in clear epoxy resin and
      sectioned into two plains. With a digital microscope, the distance between die
      and crowns was measured at the occlusal and axial walls. The horizontal/vertical
      fit at the finishing line of each section were measured as well. RESULTS: For the
      marginal fit, the analysis shows that the influence of material and design was
      significant on horizontal and vertical margins, and the influence of finish was
      significant with horizontal but not vertical margins (p=0.09). For the internal
      fit, the analysis showed that the axial gap was significantly influenced by
      material and finish but not by design (p=0.44). CONCLUSIONS: With a few
      exceptions, horizontal and vertical marginal discrepancies were below 100 MUm.
      Additional firing increased the discrepancies.

PMID- 29182216
TI  - Adhesion and Early Colonization of S. Mutans on Lithium Disilicate Reinforced
      Glass-Ceramics, Monolithic Zirconia and Dual Cure Resin Cement.
AB  - OBJECTIVE: Monolithic zirconia and glass ceramics are increasingly used in
      implant crowns. Limited data is available on bacterial adhesion and early biofilm
      formation on these materials. METHODS: Four different materials were
      investigated: (1) Lithium disilicate glass-ceramics (LDS), (2) Fully stabilized
      zirconia (FSZ), (3) Partially stabilized zirconia (PSZ), and (4) Dual curing
      cement (DCC). The materials' surfaces were characterized with spinning disc
      confocal microscopy and by water contact angle and surface free energy (SFE)
      measurements. For the adhesion tests the materials were rolled in suspensions of
      Streptococcus mutans. Early biofilm formation was studied on the materials and
      allowing the biofilms to form for 24 h. S. mutans cell counts were determined by
      plate culturing. ANOVA and post-hoc Tukey's tests (p?0.05) were used for
      statistical evaluation. RESULTS: The LDS surfaces were clearly hydrophilic with
      the highest SFE value (p?0.001). For S. mutans adhesion, the ranking of the
      materials from lowest to highest was: LDS = FSZ ? DCC ? PSZ (p?0.05). No
      significant differences among the materials were noticed in biofilm formation.
      CONCLUSIONS: LDS has lower S.mutans adhesion than other materials examined in
      this study, but the difference was not reflected in early biofilm formation.

PMID- 29182217
TI  - The Effect of Surface Preparation of Acrylic Teeth.
AB  - PURPOSE: To investigate whether the chemical bond between acrylic teeth and heat
      polymerized PMMA can be altered by chemical and/or mechanical treatment.
      MATERIALS AND METHODS: One hundred fifty acrylic teeth were divided in groups of
      10. Their ridge lap surface underwent mechanical and/or chemical treatments: 1)
      no treatment, 2) air-abrasion with Al2O3 particles, 3) acid etching with
      phosphoric acid, 4) application of composite resin bonding agent, 5) application
      of MMA and ethylmethylketone bonding agent, 6) PMMA monomer application. The
      teeth were then placed in heat polymerized acrylic resin. Each specimen was
      compressed with a universal testing machine. Descriptive statistics, one-way
      ANOVA (alpha=0.05) and Tukey's HSD test were used. A scanning electron microscope
      (SEM) was also used to study the fracture areas. RESULTS: Statistically
      significant differences (p?0.001) in the bond strength were found. The strongest
      bond (239.41 N), was noted in the group treated with sandblasting followed by
      PMMA monomer application. CONCLUSIONS: Mechanical and/or chemical preparations
      affect significantly the bond strength between the acrylic resin denture teeth
      and the PMMA denture base. Air abrasion was the most effective treatment, either
      alone or combined with other treatments.

PMID- 29182218
TI  - Hepatitis A in Poland in 2015
AB  - AIM: The aim of this article is to assess the epidemiological situation of
      Hepatitis A in Poland in 2015 with theregard to the recent years. MATERIALS AND
      METHODS: The assessment was conducted based on the results of the analysis of
      data fromthe bulletins "Infectious diseases and poisonings in Poland in 2015" and
      "Vaccinations in Poland in 2015", as wellas information from the individual cases
      questionnaires and reports of epidemiological investigations in outbreaksof
      hepatitis A, submitted by the sanitary-epidemiological stations to the Department
      of Epidemiology in NIPH-NIH. RESULTS: In 2015 in Poland there were 49 cases of
      hepatitis A registered. Incidence per 100 000 inhabitantswas 0,13, and in
      different voivodeships varied from 0,03 (in Dolnoslaskie, Malopolskie
      voivodeship) to 0,36 (inMalopolskie voivodeship). The incidence among male and
      female was similar - 0.11 i 0.15/100 000 respectively. CONCLUSIONS: In 2015
      despite the decrease in the number of cases (comparing it to the previous year)
      no significantchange in epidemiological situation of hepatitis A was observed. In
      the course of routine surveillance no informationare gathered concerning the risk
      groups affiliation of persons being vaccinated. This information would
      facilitatethe creation of recommendations for the vaccination against hepatitis A
      policy. In regard of the increase of populationsusceptible to infection the
      maintenance of high level routine surveillance in Poland gains particular
      importance.

PMID- 29182219
TI  - Hepatitis B in Poland in 2015
AB  - OBJECTIVE: Assessment of the epidemiological situation of hepatitis B in Poland
      in 2015 in relation toprevious years. MATERIAL AND METHODS: Evaluation of the
      epidemiological situation carried out based on analysisof data from individual
      reports on acute hepatitis B cases registered by the sanitary-epidemiological
      stations,aggregate data published in annual bulletins "Infectious diseases and
      poisonings in Poland" and data from annualbulletin "Vaccinations in Poland".
      RESULTS: In total, 3 518 cases of hepatitis B were registered in 2015, including
      24 cases of HBV/ HCVco-infections. Acute cases accounted for 1.5% of all recorded
      cases, with a sustained downward trend inincidence - 0.14 per 100,000. Incidence
      of acute hepatitis B was lower by 22% compared to the previous year.In group of
      children up to 14 years old, covered by universal vaccinations of neonates, 1
      acute case was reportedin a 4-month-old child. Most of acute hepatitis B
      infections (58%) were probably acquired during medicalprocedures performed in
      health care settings.The number of chronic and unknown (in terms of stage) cases
      registered increased in comparison with theprevious year, the incidence was 9.0
      per 100,000 population and was higher by 29% than in 2014. Chronicinfections and
      UNK occurred 1.3-fold more frequently in men than in women and 1.5-fold more
      frequentlyamong urban dwellers than in rural population.In 2015, three people
      died due to acute hepatitis B, and 57 people due to chronic. CONCLUSIONS: The
      changes implemented in surveillance in 2014 allow for gradual reducing of
      territorialdisparities and for assessment of the actual number of newly detected
      infections. Maintenance of a low incidenceof acute hepatitis B provides the
      premise for sustain existing preventive measures, especially universal
      vaccinationof newborns and recommendation to vaccinate of all persons previously
      unvaccinated.

PMID- 29182220
TI  - Hepatitis C in Poland in 2015
AB  - INTRODUCTION: On account of the asymptomatic course, no possibility to prevent by
      vaccination andthe serious consequences of long-term infection (liver cirrhosis,
      hepatocellular carcinoma), hepatitis C (HCVinfection) is a serious public health
      problem. OBJECTIVE: This article aims are evaluating the epidemiological
      situation of HCV infections in Poland in2015 in reference to the data from
      previous years. MATERIAL AND METHODS: Analysis of epidemiological situation of
      hepatitis C in Poland was carried outon a basis of aggregated data from routine
      surveillance system published in annual bulletin "Infectious Diseasesand
      Poisonings in Poland". Data on hepatitis C mortality from the Demographic Surveys
      and Labour MarketDepartment of the Central Statistical Office were also included.
      In 2015, mandatory reporting included: 1) HCVinfections diagnosed by physicians
      and 2) positive laboratory test results for HCV. RESULTS: In 2015, a total of
      4,285 cases were reported (diagnosis rate 11.14 per 100,000). The diagnosis
      rateincreased by 21% compared to 2014 (2014: 3 551 cases, 9.23 per 100,000) and
      doubled with respect to the medianvalue in 2009-2013 (2,189 cases, 5.68 per
      100,000). For the first time the diagnosis rates in men and women werecomparable
      (11.10 per 100,000 vs. 11.19 per 100,000). The percentage of people hospitalized
      due to HCV infection atHCV diagnosis decreased (in 2015 - 39.0%, in 2014 -
      48.4%). In 2015, 239 deaths due to hepatitis C were registered. CONCLUSIONS: The
      increased diagnosis rate of hepatitis C in 2015 may be a consequence of improved
      reporting,legislative changes (introduction of mandatory reporting of positive
      laboratory results) as well as enhanced publicityand other HCV control
      activities, including increased availability of HCV laboratory screening.

PMID- 29182221
TI  - Tetanus in Poland in 2015
AB  - : The number of tetanus in the 21st century shows a slight declining trend, but
      each year there is reported fatalcases of this disease. THE PURPOSE of the STUDY:
      The purpose of the study is to provide data on epidemiological surveillanceof the
      tetanus in 2015. MATERIAL AND METHODS: The study is based on the individual forms
      of tetanus cases submitted to theNIZP-PZH Epidemiology Department and the data of
      the bulletin "Infectious Diseases and Poisoning in Polandin 2015. RESULTS: In
      2015, 12 cases of tetanus were reported. Six men and six women became ill. 4
      people died after69 years of age. SUMMARY AND CONCLUSIONS: Tetanus is an
      infectious disease acquired in the environment andassociated with wound
      contamination. Infections can be prevented by vaccination. Particularly threat to
      life andhealth carries disease in the late age.

PMID- 29182222
TI  - HIV and AIDS in Poland in 2015
AB  - AIM: AIM. The aim was to describe the epidemiological situation of newly
      diagnosed HIV infections and AIDS casesin Poland in 2015 in comparison to the
      previous years. MATERIALS AND METHODS: Descriptive analysis of newly detected HIV
      cases and AIDS cases wasperformed based on routine notifications by clinicians
      and laboratories. Data on the number of HIV tests fromannual survey among
      laboratories were also used. RESULTS: In 2015 there were 1,281 HIV cases newly
      diagnosed in Poland (diagnosis rate 3.33 per 100,000 population),including 23
      among non-Polish citizens. The rate of new cases rose by 15% compared to the
      previous year as well as tothe median in 2009 - 2013. The total number of AIDS
      cases was 128 (incidence 0.38 per 100,000) and 41 AIDS patientsdied (0.11 per
      100,000). HIV infection was mainly detected among people aged from 20 to 39 years
      (71.3%) and amongmales (84.8%). Among men, 67.6% of newly diagnosed infections
      with known transmission category were acquired bymen who have sex with men (MSM).
      The percentage of infected men in this group, compared to 2014, increased
      from64.5% to 67.6%. The percentage of newly diagnosed persons infected by
      heterosexual contact decreased from 24.1% to21.1% (persons with known
      transmission category). The percentage of people with HIV diagnosed at the same
      time asAIDS diagnosed decreased in comparison with 2014 (from 9.2% to 6.9% of
      newly detected HIV infections). CONCLUSIONS: HIV epidemic continues to develop
      among MSM in Poland. However, assessment ofepidemiological situation is limited
      by the missing data on the probable transmission route in a large percentageof
      reported newly detected HIV infection.

PMID- 29182223
TI  - Tuberculosis in Poland in 2015
AB  - AIM OF THE STUDY: To evaluate the main features of TB epidemiology in 2015 in
      Poland and to compare withthe data on the same phenomena in the EU/EEA countries.
      METHODS: Analysis of case - based data on TB patients from National TB Register,
      data on anti-TB drugsusceptibility testing results in cases notified in 2015,
      data from National Institute of Public Health- National Instituteof Hygiene on
      cases of tuberculosis as AIDS-defining disease, data from Central Statistical
      Office on deaths fromtuberculosis based on death certificates, data from ECDC
      report " European Centre for Disease Prevention andControl/WHO Regional Office
      for Europe. Tuberculosis surveillance and monitoring in Europe 2017.
      Stockholm:European Centre for Disease Prevention and Control, 2017". RESULTS:
      6430 TB cases were reported in Poland in 2015. The incidence rate was 16.7 cases
      per 100 000, withlarge variability between voivodeships from 8.3 to 26.5 per 100
      000. The mean annual decrease of TB incidencein 2011- 2015 was 5.5%. 5757 cases
      were new, never treated i.e. 15.0 per 100 000. 673 cases i.e. 1.8 per 100 000 
      10.5% of all registered subjects were previously treated.The number of all
      notified pulmonary tuberculosis cases in 2015 was 6078 i.e. 15.8 per 100 000.
      Pulmonary casesrepresented 94.5% of all TB cases. The number of pulmonary TB
      cases with bacteriological confirmation was 4472i.e. 11,6 per 100 000. In 2015,
      only 352 extrapulmonary TB cases were reported. Children accounted for 1.3% ofall
      TB cases in Poland; 81 pediatric cases were notified. The incidence of
      tuberculosis has been growing along withthe age group from 1.4 per 100 000 among
      children to 28.1 per 100 000 among patients aged 45 to 64 years. In theage group
      65 years old and older the incidence was 26.9 per 100 000.The incidence among men
      i.e. 24.0 per 100 000 was >2 times higher than among women i.e. 9.9 per 100 000.
      Thebiggest difference in the TB incidence between the two sex groups occurred in
      persons aged 50 to 54 years - 45.6vs. 12.4 and in subjects aged 55 to 59 years
      (53.3 vs. 12.8). The TB incidence in rural population was lower than inurban,
      respectively 16.5 per 100 000 and 16.9 per 100 000.The number of all registered
      culture positive TB cases, including cases previously treated, was 4630.
      Cultureconfirmedcases constituted 72.0% of all TB cases; culture-confirmed
      pulmonary TB - 73.6% of all pulmonary TBcases. The number of smear
      positive/culture positive pulmonary TB cases reported in 2015 was 2714 i.e. 7.1
      per100 000 respectively what constituted 44.7% of all pulmonary TB cases.TB was
      initial AIDS indicative disease in 20 persons. In Poland in 2015 there were 35
      cases with MDR-TB (amongthem 5 foreigners) and 95 patients with resistance solely
      to isoniazid, constituting respectively 0.8% and 2.3% ofcases with known DST
      results (DSTs were done in 91.6% of all culture-confirmed TB cases). There were
      52 casesof tuberculosis registered among foreigners in 2015.There were 526 deaths
      due to tuberculosis reported in 2014 - 1.4 per 100 000; 504 people died from
      pulmonaryand 22 from extrapulmonary tuberculosis. Mortality among males - 2.2 per
      100 000 - was 3.6 x higher than amongfemales - 0.6. The highest mortality rate
      was in subjects 65 years old and older - 3.8 per 100 000. There were nodeaths
      from tuberculosis in children. TB was cause of death in one adolescent. TB
      mortality in 2014 constituted0.14% of total mortality in Poland and 27.4% of
      mortality from infectious diseases. CONCLUSIONS: In Poland in 2015 the incidence
      of tuberculosis was lower than in the past but higher than theaverage in the
      EU/EEA countries. The highest incidence rates occurred in older age groups. The
      incidence in menwas more than 2 times higher than in women. In Poland,
      tuberculosis in children, tuberculosis in persons infectedwith HIV and MDR-TB are
      less common than in the EU/EEA countries.

PMID- 29182224
TI  - International Expansion. New JEMS content and EMS Today conference sessions allow
      you to expand your EMS horizon and improve your EMS System.

PMID- 29182225
TI  - He's Dying to Tell You. Will his last words help convict his killer?

PMID- 29182227
TI  - Hearing Voices. Safely treating patients with schizophrenia.

PMID- 29182226
TI  - Culture of Respect. Misuse of patient images isn't just about the law.

PMID- 29182229
TI  - Vaccine Standard. Providers have a responsibility to be vaccinated against
      influenza.

PMID- 29182228
TI  - Unexpected Transmission. Standard PPE can't prevent all viruses from spreading.

PMID- 29182230
TI  - CBCT for Full-Arch Implant Dental Treatment.

PMID- 29182231
TI  - Custom Abutments and Monolithic Zirconia: Aesthetic, Cementable Solutions for
      Complete Edentulism.

PMID- 29182232
TI  - The Case For An EMS Sepsis Detection and Alert Protocol.

PMID- 29182233
TI  - On the Front Line of Sepsis: Lifesaving sepsis identification and hospital alerts
      in Polk County, Fla.

PMID- 29182234
TI  - Implant Overdentures: Guidelines for Immediate Loading.

PMID- 29182235
TI  - Miami Sepsis Score: New evidence-based prehospital sepsis identification tool.

PMID- 29182236
TI  - Single-Visit Chairside Zirconia.

PMID- 29182237
TI  - Direct Composite Veneering: A Case Retrospective.

PMID- 29182238
TI  - Intensive Blood-Pressure Treatment and Patient-Reported Outcomes.

PMID- 29182239
TI  - Chemical Welding on Semimetallic TiS2 Nanosheets for High-Performance Flexible n
      Type Thermoelectric Films.
AB  - Solution-based processing of two-dimensional (2D) materials provides the
      possibility of allowing these materials to be incorporated into large-area thin
      films, which can translate the interesting fundamental properties of 2D materials
      into available devices. Here, we report for the first time a novel chemical
      welding method to achieve high-performance flexible n-type thermoelectric films
      using 2D semimetallic TiS2 nanosheets. We employ chemically exfoliated TiS2
      nanosheets bridged with multivalent cationic metal Al3+ to cross-link the nearby
      sheets during the film deposition process. We find that such a treatment can
      greatly enhance the stability of the film and can improve the power factor by
      simultaneously increasing the Seebeck coefficient and electrical conductivity.
      The resulting TiS2 nanosheet-based flexible film shows a room temperature power
      factor of ~216.7 MUW m-1 K-2, which is among the highest chemically exfoliated 2D
      transition-metal dichalcogenide nanosheet-based films and comparable to the best
      flexible n-type thermoelectric films, to our knowledge, indicating its potential
      applications in wearable electronics.

PMID- 29182240
TI  - Ag Nanoparticle-Based Triboelectric Nanogenerator To Scavenge Wind Energy for a
      Self-Charging Power Unit.
AB  - Li-ion batteries are a green energy storage technology with advantages of high
      energy density, long lifetime, and sustainability, but they cannot generate
      electric energy by themselves. As a novel energy-harvesting technology,
      triboelectric nanogenerators (TENGs) are a promising power source for supplying
      electronic devices, however it is difficult to directly use their high output
      voltage and low output current. Here, we designed a Ag nanoparticle-based TENG
      for scavenging wind energy. After including a transformer and a power management
      circuit into the system, constant output voltages such as 3.6 V and a pulsed
      current of about 100 mA can be obtained, which can be used to directly light up a
      light-emitting diode. Furthermore, the produced electric energy can be
      effectively stored in a WO3/LiMn2O4 electrode based Li-ion battery. Our present
      work provides a new approach to effectively scavenge wind energy and store the
      obtained electric energy, which is significant for exploring self-charging power
      units.

PMID- 29182241
TI  - Ultrathin Plasmonic Optical/Thermal Barrier: Flashlight-Sintered Copper
      Electrodes Compatible with Polyethylene Terephthalate Plastic Substrates.
AB  - In recent years, highly conductive, printable electrodes have received tremendous
      attention in various research fields as the most important constituent components
      for large-area, low-cost electronics. In terms of an indispensable sintering
      process for generating electrodes from printable metallic nanomaterials, a
      flashlight-based sintering technique has been regarded as a viable approach for
      continuous roll-to-roll processes. In this paper, we report cost-effective,
      printable Cu electrodes that can be applied to vulnerable polyethylene
      terephthalate (PET) substrates, by incorporating a heretofore-unrecognized
      ultrathin plasmonic thermal/optical barrier, which is composed of a 30 nm thick
      Ag nanoparticle (NP) layer. The different plasmonic behaviors during a flashlight
      sintering process are investigated for both Ag and Cu NPs, based on a combined
      interpretation of the experimental results and theoretical calculations. It is
      demonstrated that by a continuous printing process and a continuous flashlight
      sintering process, the Cu electrodes are formed successfully on large PET
      substrates, with a sheet resistance of 0.24 Omega/sq and a resistivity of 22.6
      MUOmega.cm.

PMID- 29182242
TI  - Synergistic Effect of Partially Fluorinated Ether and Fluoroethylene Carbonate
      for High-Voltage Lithium-Ion Batteries with Rapid Chargeability and
      Dischargeability.
AB  - The roles of a partially fluorinated ether (PFE) based on a mixture of
      1,1,1,2,2,3,3,4,4-nonafluoro-4-methoxybutane and 2-(difluoro(methoxy)methyl)
      1,1,1,2,3,3,3-heptafluoropropane on the oxidative durability of an electrolyte
      under high-voltage conditions, the rate capability of the graphite and 5 V-class
      LiNi0.4Mn1.6O4 (LNMO) electrodes, and the cycling performance of graphite/LNMO
      full cells are examined. Our findings indicate that the use of PFE as a cosolvent
      in the electrolyte yields thermally stable electrolytes with self-extinguishing
      ability. Electrochemical tests confirm that the PFE combined with fluoroethylene
      carbonate (FEC) effectively alleviates the oxidative decomposition of the
      electrolyte at the high-voltage LNMO cathode and enables reversible
      electrochemical reactions of the graphite anodes and LNMO cathodes at high rates.
      Moreover, the combination of PFE, which mitigates electrolyte decomposition at
      high voltages, and FEC, which stabilizes the anode-electrolyte interface, enables
      the reversible cycling of high-voltage full cells (graphite/LNMO) with a capacity
      retention of 70.3% and a high Coulombic efficiency of 99.7% after 100 cycles at
      1C rate at 30  degrees C.

PMID- 29182243
TI  - Targeting the Thioredoxin Reductase-Thioredoxin System from Staphylococcus aureus
      by Silver Ions.
AB  - The thioredoxin system, which is composed of NADPH, thioredoxin reductase (TrxR),
      and thioredoxin (Trx), is one of the major disulfide reductase systems used by
      bacteria against oxidative stress. In particular, this reductase system is
      crucial for the survival of the pathogenic bacterium Staphylococcus aureus, which
      lacks a natural glutathione/glutaredoxin (Grx) system. Although silver ions and
      silver-containing materials have been used as antibacterial agents for centuries,
      the antibacterial mechanism of silver is not well-understood. Herein, we
      demonstrate that silver ions bind to the active sites of S. aureus TrxR and Trx
      with dissociation constants of 1.4 +/- 0.1 MUM and 15.0 +/- 5.0 MUM and
      stoichiometries of 1 and 2 Ag+ ions per protein, respectively. Importantly,
      silver ion binding leads to oligomerization and functional disruption of TrxR as
      well as Trx. Silver also depleted intracellular thiol levels in S. aureus,
      disrupting bacterial thiol-redox homeostasis. Our study provides new insights
      into the antibacterial mechanism of silver ions. Moreover, the Trx and TrxR
      system might serve as a feasible target for the design of antibacterial drugs.

PMID- 29182245
TI  - Molecular "Flower" as the High-Mobility Hole-Transport Material for Perovskite
      Solar Cells.
AB  - To develop novel hole-transport materials (HTMs) with less synthetic steps is
      still a great challenge. Here, a small molecule hexakis[4-(N,N-di-p
      methoxyphenylamino)phenyl]benzene (F-1) was successfully synthesized by a
      relatively simple scenario. F-1 exhibits a deep highest occupied molecular
      orbital energy level of -5.31 eV. Notably, F-1 also features 2 times higher hole
      mobility of 4.98 * 10-4 cm2 V-1 s-1 than that of the mostly used 2,2',7,7'
      tetrakis(N,N-bis(4-methoxyphenyl)amino)-9,9'-spirobifluorene (spiro-OMeTAD).
      Consequently, F-1-based perovskite solar cells (PSCs) show markedly improved
      performance compared with spiro-OMeTAD-based ones. These results indicate such a
      material can be a promising HTM candidate to boost the overall performance of the
      PSC.

PMID- 29182244
TI  - Allosteric Modulation of Grb2 Recruitment to the Intrinsically Disordered
      Scaffold Protein, LAT, by Remote Site Phosphorylation.
AB  - Tyrosine phosphorylation of membrane receptors and scaffold proteins followed by
      recruitment of SH2 domain-containing adaptor proteins constitutes a central
      mechanism of intracellular signal transduction. During early T-cell receptor
      (TCR) activation, phosphorylation of linker for activation of T cells (LAT)
      leading to recruitment of adaptor proteins, including Grb2, is one prototypical
      example. LAT contains multiple modifiable sites, and this multivalency may
      provide additional layers of regulation, although this is not well understood.
      Here, we quantitatively analyze the effects of multivalent phosphorylation of LAT
      by reconstituting the initial reactions of the TCR signaling pathway on supported
      membranes. Results from a series of LAT constructs with combinatorial mutations
      of tyrosine residues reveal a previously unidentified allosteric mechanism in
      which the binding affinity of LAT:Grb2 depends on the phosphorylation at remote
      tyrosine sites. Additionally, we find that LAT:Grb2 binding affinity is altered
      by membrane localization. This allostery mainly regulates the kinetic on-rate,
      not off-rate, of LAT:Grb2 interactions. LAT is an intrinsically disordered
      protein, and these data suggest that phosphorylation changes the overall ensemble
      of configurations to modulate the accessibility of other phosphorylated sites to
      Grb2. Using Grb2 as a phosphorylation reporter, we further monitored LAT
      phosphorylation by TCR zeta chain-recruited ZAP-70, which suggests a weakly
      processive catalysis on membranes. Taken together, these results suggest that
      signal transmission through LAT is strongly gated and requires multiple
      phosphorylation events before efficient signal transmission is achieved.

PMID- 29182246
TI  - Prehospital Antibiotics. Greenville, S.C. brings definitive sepsis care into the
      ambulance.

PMID- 29182247
TI  - Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.

PMID- 29182248
TI  - EtCO2 to Identify Severe Sepsis: Prehospital sepsis screening and ED alerts in
      Orange County, Fla.

PMID- 29182249
TI  - Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.

PMID- 29182250
TI  - Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.

PMID- 29182251
TI  - Porphyria.

PMID- 29182252
TI  - EtCO2 and Lactate: Correlation may be key to early sepsis detection.

PMID- 29182253
TI  - Porphyria.

PMID- 29182254
TI  - Greater Emphasis: Wake County, N.C., strives for prehospital recognition and
      treatment of sepsis.

PMID- 29182255
TI  - More on Anti-CD19 CAR T Cells in CNS Diffuse Large-B-Cell Lymphoma.

PMID- 29182256
TI  - Image-Guided Endodontics: The Role of the Endodontic Triad.

PMID- 29182257
TI  - Er,Cr:YSGG Laser-Assisted Periodontal Treatment.

PMID- 29182258
TI  - Multidisciplinary Management of Oligodontia in the Adolescent.

PMID- 29182259
TI  - Incommensurability in Endodontics: The Role of the Endodontic Triad.

PMID- 29182260
TI  - An implant focus for the general practitioner.

PMID- 29182261
TI  - Focus on: Hands-on education.

PMID- 29182262
TI  - Pediatric Sepsis: A killer worldwide and at home.

PMID- 29182263
TI  - Sepsis Down Under: Sepsis care and treatment in New Zealand and Australia.

PMID- 29182264
TI  - Healthcare Anxiety: Educate the public on when to call 9-1-1.

PMID- 29182265
TI  - Last Word: The Ups and Downs of EMS.

PMID- 29182266
TI  - Asymmetric Nanochannel-Ionchannel Hybrid for Ultrasensitive and Label-Free
      Detection of Copper Ions in Blood.
AB  - Nanochannel/nanopre based analysis methods have attracted increasing interest in
      recent years due to their exquisite ability to reveal changes in molecular
      volume. In this work, a highly asymmetric nanochannel-ionchannel hybrid coupled
      with an electrochemical technique was developed for copper ion (Cu2+) detection.
      Polyglutamic acid (PGA) was modified in a nanochannel array of porous anodic
      alumina (PAA). When different concentrations of Cu2+ were introduced into the
      nanochannel-ionchannel hybrid in a neutral environment, a Cu2+-PGA chelation
      reaction occurs, resulting in varied current-potential (I-V) properties of the
      nanochannel-ionchannel hybrid. When PAA was immersed in a low pH solution, the
      Cu2+-PGA complex dissociated. On the basis of the change in ionic current, a
      label-free assay for Cu2+ was achieved along with the ability to regenerate and
      reuse the constructed platform. Because of the unique mass transfer property of
      the nanochannel-ionchannel hybrid combined with the highly amplified ionic
      current magnitude of the nanochannel array, significantly increased assay
      sensitivity was achieved, as expected. To evaluate the applicability of the
      present methodology for detecting Cu2+ in a real sample, the Cu2+ content in real
      blood samples was analyzed. The results demonstrate that the present method shows
      excellent selectivity with high sensitivity toward Cu2+ detection in real blood
      samples.

PMID- 29182267
TI  - An Improved Whole-Cell Biosensor for the Discovery of Lignin-Transforming Enzymes
      in Functional Metagenomic Screens.
AB  - The discovery and utilization of biocatalysts that selectively valorize
      lignocellulose is critical to the profitability of next-generation biorefineries.
      Here, we report the development of a refactored, whole-cell, GFP-based biosensor
      for high-throughput identification of biocatalysts that transform lignin into
      specialty chemicals from environmental DNA of uncultivable archaea and bacteria.
      The biosensor comprises the transcriptional regulator and promoter of the emrRAB
      operon of E. coli, and the configuration of the biosensor was tuned with the aid
      of mathematical model. The biosensor sensitively and selectively detects vanillin
      and syringaldehyde, and responds linearly over a wide detection range. We
      employed the biosensor to screen 42 520 fosmid clones comprising environmental
      DNA isolated from two coal beds and successfully identified 147 clones that
      transform hardwood kraft lignin to vanillin and syringaldehyde.

PMID- 29182268
TI  - Core Richness of N-Glycans of Caenorhabditis elegans: A Case Study on Chemical
      and Enzymatic Release.
AB  - Despite years of research, the glycome of the model nematode Caenorhabditis
      elegans is still not fully understood. Certainly, data over the years have
      indicated that this organism synthesizes unusual N-glycans with a range of
      galactose and fucose modifications on the Man2-3GlcNAc2 core region. Previously,
      up to four fucose residues were detected on its N-glycans, despite these lacking
      the fucosylated antennae typical of many other eukaryotes; some of these fucose
      residues are capped with hexose residues as shown by the studies of us and
      others. There have, though, been contrasting reports regarding the maximal number
      of fucose substitutions in C. elegans, which in part may be due to different
      methodological approaches, including use of either peptide:N-glycosidases F and A
      (PNGase F and A) or anhydrous hydrazine to cleave the N-glycans from
      glycopeptides. Here we compare the use of hydrazine with that of a new enzyme
      (rice PNGase Ar) and show that both enable release of glycans with more sugar
      residues on the proximal GlcNAc than previously resolved. By use of
      exoglycosidase sequencing, in conjunction with high-performance liquid
      chromatography (HPLC) and matrix-assisted laser desorption ionization time-of
      flight tandem mass spectrometry (MALDI-TOF MS/MS), we now reveal that actually up
      to five fucose residues modify the core region of C. elegans N-glycans and that
      the alpha1,3-fucose on the reducing terminus can be substituted by an alpha
      linked galactose. Thus, traditional PNGase F and A release may be insufficient
      for release of the more highly core-modified N-glycans, especially those
      occurring in C. elegans, but novel enzymes can compete against chemical methods
      in terms of safety, ease of cleanup, and quality of resulting glycomic data.

PMID- 29182269
TI  - Multistability at Room Temperature in a Bent-Shaped Spin-Crossover Complex
      Decorated with Long Alkyl Chains.
AB  - An iron(II) pyridyl-benzohydrazonate-based complex decorated with long alkyl
      chains is reported as a rare spin-crossover compound displaying a wide thermal
      hysteresis spanning room temperature. On heating, this compound exhibits a spin
      transition between a LS ground state and an ordered HS-LS phase with symmetry
      breaking from monoclinic P21/n into orthorhombic P21212 space groups. During
      cooling, the compound first transits into a magnetically distinguishable HS-LS
      phase with monoclinic P21 symmetry before returning into the LS phase.
      Interconversion between the two distinct HS-LS phases is the result of subtle
      structural changes in the alkyl chains and produces a second minor thermal
      hysteresis that superposes to the large one. This unprecedented result shows that
      the combination of a conventional cooperative spin transition and ligand-driven
      magnetic changes can promote magnetic tristability at room temperature.

PMID- 29182270
TI  - Advances in the Chemical Biology of Desferrioxamine B.
AB  - Desferrioxamine B (DFOB) was discovered in the late 1950s as a hydroxamic acid
      metabolite of the soil bacterium Streptomyces pilosus. The exquisite affinity of
      DFOB for Fe(III) identified its potential for removing excess iron from patients
      with transfusion-dependent hemoglobin disorders. Many studies have used
      semisynthetic chemistry to produce DFOB adducts with new properties and broad
      ranging functions. More recent approaches in chemical biology have revealed some
      nuances of DFOB biosynthesis and discovered new DFOB-derived drugs and radiometal
      imaging agents. The current and potential applications of DFOB continue to
      inspire a rich body of chemical biology research focused on this bacterial
      metabolite.

PMID- 29182271
TI  - Regio- and Chemoselective Hydrogenation of Dienes to Monoenes Governed by a Well
      Structured Bimetallic Surface.
AB  - Unprecedented surface chemistry, governed by specific atomic arrangements and the
      steric effect of ordered alloys, is reported. Rh-based ordered alloys supported
      on SiO2 (RhxMy/SiO2, M = Bi, Cu, Fe, Ga, In, Pb, Sn, and Zn) were prepared and
      tested as catalysts for selective hydrogenation of trans-1,4-hexadiene to trans-2
      hexene. RhBi/SiO2 exhibited excellent regioselectivity for the terminal C?C bond
      and chemoselective hydrogenation to the monoene, not to the overhydrogenated
      alkane, resulting in a high trans-2-hexene yield. Various asymmetric dienes,
      including terpenoids, were converted into the corresponding inner monoenes in
      high yields. This is the first example of a regio- and chemoselective
      hydrogenation of dienes using heterogeneous catalysts. Kinetic studies and
      density functional theory calculations revealed the origin of the high
      selectivity: (1) one-dimensionally aligned Rh arrays geometrically limit hydrogen
      diffusion and attack to alkenyl carbons from one direction and (2) adsorption of
      the inner C?C moiety to Rh is inhibited by steric repulsion from the large Bi
      atoms. The combination of these effects preferentially hydrogenates the terminal
      C?C bond and prevents overhydrogenation to the alkane.

PMID- 29182272
TI  - Ex Vivo Tracking of Endogenous CO with a Ruthenium(II) Complex.
AB  - A two-photon fluorescent probe based on a ruthenium(II) vinyl complex is capable
      of selectively detecting carbon monoxide in cells and ex vivo using mice with a
      subcutaneous air pouch as a model for inflammation. This probe combines highly
      selective and sensitive ex vivo detection of endogenous CO in a realistic model
      with facile, inexpensive synthesis, and displays many advantages over the widely
      used palladium-based systems.

PMID- 29182273
TI  - Structural Investigation of a Dimeric Variant of Pyruvate Kinase Muscle Isoform
      2.
AB  - Pyruvate kinase muscle isoform 2 (PKM2) catalyzes the terminal step in
      glycolysis, transferring a phosphoryl group from phosphoenolpyruvate to ADP, to
      produce pyruvate and ATP. PKM2 activity is allosterically regulated by fructose
      1,6-bisphosphate (FBP), an upstream glycolytic intermediate. FBP stabilizes the
      tetrameric form of the enzyme. In its absence, the PKM2 tetramers dissociate,
      yielding a dimer-monomer mixture having lower enzymatic activity. The S437Y
      variant of PKM2 is incapable of binding FBP. Consistent with that defect, we find
      that S437Y exists in a monomer-dimer equilibrium in solution, with a Kd of ~20
      MUM. Interestingly, however, the protein crystallizes as a tetramer, providing
      insight into the structural basis for impaired FBP binding of S437Y.

PMID- 29182274
TI  - Organic Photosensitizers Incorporating Rigid Benzo[1,2-b:6,5-b']dithiophene
      Segment for High-Performance Dye-Sensitized Solar Cells.
AB  - Benzo[1,2-b:6,5-b']dithiophene (BDT) entity with rigid skeleton is introduced
      into the conjugated spacer of organic dyes, with triphenylamine as the electron
      donor and 2-cyanoacrylic acid as the acceptor, have been prepared for dye
      sensitized solar cells. Inserting an aromatic entity between BDT and the anchor
      extends the absorption wavelength of the dyes and improves the dark current
      suppression efficiency, and consequently leads to better cell performance.
      Addition of chenodeoxycholic acid coadsorbent alleviates dye aggregation and
      results in better cell efficiency. The dye inserted with 4H-cyclopenta[2,1-b:3,4
      b']dithiophene entity achieves the best efficiency (9.11%) when I-/I3- was used
      as the electrolyte. When Co(phen)32+/3+ was used as the electrolyte, the
      efficiency further boosts to 9.88%.

PMID- 29182275
TI  - Remarkable Roles of Cu To Synergistically Optimize Phonon and Carrier Transport
      in n-Type PbTe-Cu2Te.
AB  - High thermoelectric performance of n-type PbTe is urgently needed to match its p
      type counterpart. Here, we show a peak ZT ~ 1.5 at 723 K and a record high
      average ZT > 1.0 at 300-873 K realized in n-type PbTe by synergistically
      suppressing lattice thermal conductivity and enhancing carrier mobility by
      introducing Cu2Te inclusions. Cu performs several outstanding roles: Cu atoms
      fill the Pb vacancies and improve carrier mobility, contributing to an
      unexpectedly high power factor of ~37 MUW cm-1 K-2 at 423 K; Cu atoms filling Pb
      vacancies and Cu interstitials both induce local disorder and, together with nano
      and microscale Cu-rich precipitates and their related strain fields, lead to a
      very low lattice thermal conductivity of ~0.38 Wm-1 K-1 in PbTe-5.5%Cu2Te,
      approaching the theoretical minimum value of ~0.36 Wm-1 K-1. This work provides
      an effective strategy to enhance thermoelectric performance by simultaneously
      improving electrical and thermal transport properties.

PMID- 29182276
TI  - Identifying Structure in Short DNA Scaffolds Using Solid-State Nanopores.
AB  - The identification of molecular tags along nucleic acid sequences has many
      potential applications in bionanotechnology, disease biomarker detection, and DNA
      sequencing. An attractive approach to this end is the use of solid-state
      nanopores, which can electrically detect molecular substructure and can be
      integrated into portable lab-on-a-chip sensors. We present here a DNA origami
      based approach of molecular assembly in which solid-state nanopores are capable
      of differentiating 165 bp scaffolds containing zero, one, and two dsDNA
      protrusions. This highly scalable technique requires minimal sample preparation
      and is customizable for a wide range of targets and applications. As a proof-of
      concept, an aptamer-based DNA displacement reaction is performed in which a dsDNA
      protrusion is formed along a 255 bp scaffold in the presence of ATP. While ATP is
      too small to be directly sensed using conventional nanopore methods, our approach
      allows us to detect ATP by identifying molecular substructure along the DNA
      scaffold.

PMID- 29182277
TI  - Overall Content of Salicylic Acid and Salicylates in Food Available on the
      European Market.
AB  - The study aimed to determine the salicylates content in 112 products available on
      the European market. Quantitative determination of free and conjugated forms of
      salicylic acid in food was performed using reversed-phase high-performance liquid
      chromatography with fluorescence detection. The salicylates contents ranged from
      0 to 1675.79 (MUg/100 g). The results of this study confirm the presence of
      salicylates in food products, as well as a broad content diversity of these
      compounds depending on the species, variety, and method of processing the food
      items. The results can be very helpful for nutritionists and dieticians in
      planning low-salicylates or high-salicylates diets.

PMID- 29182278
TI  - Understanding How Sterols Regulate Membrane Remodeling in Supported Lipid
      Bilayers.
AB  - The addition of single-chain lipid amphiphiles such as antimicrobial fatty acids
      and monoglycerides to confined, two-dimensional phospholipid bilayers can trigger
      the formation of three-dimensional membrane morphologies as a passive means to
      regulate stress. To date, relevant experimental studies have been conducted using
      pure phospholipid compositions, and extending such insights to more complex,
      biologically relevant lipid compositions that include phospholipids and sterols
      is warranted because sterols are important biological mediators of membrane
      stress relaxation. Herein, using the quartz crystal microbalance-dissipation (QCM
      D) technique, we investigated membrane remodeling behaviors triggered by the
      addition of sodium dodecyl sulfate (SDS), lauric acid (LA), and glycerol
      monolaurate (GML) to supported lipid bilayers (SLBs) composed of phospholipid and
      cholesterol mixtures. The SLB platforms were prepared by the solvent-assisted
      lipid bilayer method in order to form cholesterol-rich SLBs with tunable
      cholesterol fractions (0-52 mol %). The addition of SDS or LA to fabricated SLBs
      induced tubule formation, and the extent of membrane remodeling was greater in
      SLBs with higher cholesterol fractions. In marked contrast, GML addition led to
      bud formation, and the extent of membrane remodeling was lower in SLBs with
      higher cholesterol fractions. To explain these empirical observations, we discuss
      how cholesterol influences the elastic (stiffness) and viscous (stress
      relaxation) properties of phospholipid/cholesterol lipid bilayers as well as how
      the membrane translocation properties of single-chain lipid amphiphiles affect
      the corresponding membrane morphological responses. Collectively, our findings
      demonstrate that single-chain lipid amphiphiles induce highly specific membrane
      morphological responses across both simplified and complex model membranes, and
      cholesterol can promote or inhibit membrane remodeling by a variety of molecular
      mechanisms.

PMID- 29182281
TI  - Extension of the Polarizable Charge Equilibration Model to Higher Oxidation
      States with Applications to Ge, As, Se, Br, Sn, Sb, Te, I, Pb, Bi, Po, and At
      Elements.
AB  - We recently developed the polarizable charge equilibration (PQEq) model to
      predict accurate electrostatic interactions for molecules and solids and
      optimized parameters for H, C, N, O, F, Si, P, S, and Cl elements to fit
      polarization energies computed by quantum mechanics (QM). Here, we validate and
      optimize the PQEq parameters for other p-block elements including Ge, As, Se, Br,
      Sn, Sb, Te, I, Pb, Bi, Po, and At using 28 molecular structures containing these
      elements. For these elements, we now include molecules with higher oxidation
      states: III and V for the As column, IV and VI for the Se column, and I, III, and
      V for the Br column. We find that PQEq predicts polarization energies in
      excellent agreement with QM.

PMID- 29182279
TI  - Aminomethylation of Fullerene C60 with N,N',N"-Triaryl- or N,N',N"-Trihetaryl
      1,3,5-perhydrotriazines in the Presence of EtMgBr and Ti(Oi-Pr)4.
AB  - A new method for the functionalization of fullerenes based on the reaction
      between in situ generated aryl- or hetaryl-containing 1,3,5-perhydrotriazines and
      EtMgBr in the presence of Ti(Oi-Pr)4 has been developed. The cleavage of the
      triazine ring under previously developed conditions1-6 results in the formation
      of aminomethylated derivatives of fullerene C60 with high yields (80-90%) and
      selectivity (~90%).

PMID- 29182282
TI  - Structural Effects on the pH-Dependent Redox Properties of Organic Nitroxyls:
      Pourbaix Diagrams for TEMPO, ABNO, and Three TEMPO Analogs.
AB  - Electrochemical studies of the reduction and oxidation reactions of five
      different organic nitroxyls have been performed across a wide pH range (0-13).
      The resulting Pourbaix diagrams illustrate structural effects on their various
      redox potentials and on the p Ka values of the corresponding hydroxylamine and
      hydroxylammonium ions. Evidence is also given for the reversible formation of a
      hydroxylamine N-oxide when nitroxyls are oxidized in alkaline media. Structural
      effects on the thermodynamics of this reaction are assessed.

PMID- 29182283
TI  - Selective Single C(sp3)-F Bond Cleavage in Trifluoromethylarenes: Merging Visible
      Light Catalysis with Lewis Acid Activation.
AB  - The conversion of easily available trifluoromethylarenes into aryldifluoromethyl
      compounds, which are valuable motifs in the pharmaceutical chemistry, is highly
      atom- and step-economical. However, the single C(sp3)-F bond cleavage of ArCF3 is
      a great challenge because of the chemical inertness of the C(sp3)-F bond and the
      difficult selectivity control of monodefluorination. We report here the first
      example of single C(sp3)-F functionalization of trifluoromethylarenes via visible
      light catalysis merged with Lewis acid activation. The method allows good
      chemoselectivity control and shows good functional group tolerance. Mechanistic
      studies suggest an in situ-generated borenium cationic species as the key
      intermediate for C(sp3)-F bond cleavage in this reaction.

PMID- 29182284
TI  - Reconstructing the Surface of Gold Nanoclusters by Cadmium Doping.
AB  - Atomically precise metal nanoclusters with tailored surface structures are
      important for both fundamental studies and practical applications. The
      development of new methods for tailoring the surface structure in a controllable
      manner has long been sought. In this work, we report surface reconstruction
      induced by cadmium doping into the [Au23(SR)16]- (R = cyclohexyl) nanocluster, in
      which two neighboring surface Au atomic sites "coalesce" into one Cd atomic site
      and, accordingly, a new bimetal nanocluster, [Au19Cd2(SR)16]-, is produced.
      Interestingly, a Cd(S-Au-S)3 "paw-like" surface motif is observed for the first
      time in nanocluster structures. In such a motif, the Cd atom acts as a junction
      which connects three monomeric -S-Au-S- motifs. Density functional theory
      calculations are performed to understand the two unique Cd locations.
      Furthermore, we demonstrate different doping modes when the [Au23(SR)16]-
      nanocluster is doped with different metals (Cu, Ag), including (i) simple
      substitution and (ii) total structure transformation, as opposed to surface
      reconstruction for Cd doping. This work greatly expands doping chemistry for
      tailoring the structures of nanoclusters and is expected to open new avenues for
      designing nanoclusters with novel surface structures using different dopants.

PMID- 29182285
TI  - Enantioselective Total Synthesis of (+)-Gephyrotoxin 287C.
AB  - A synthesis of (+)-gephyrotoxin 287C using (S)-phenylglycinol-derived tricyclic
      lactam 7 as the starting enantiomeric scaffold is reported. From the
      stereochemical standpoint, the key steps are the generation of the DHQ C-5
      stereocenter by hydrogenation of the C-C double bond, removal of the chiral
      inductor to give a cis-DHQ, introduction of the DHQ C-2 substituent, completion
      of the (Z)-enyne moiety, and generation of the C-1 stereocenter during closure of
      the pyrrolidine ring.

PMID- 29182286
TI  - A Fe(III)/NaBH4-Promoted Free-Radical Hydroheteroarylation of Alkenes.
AB  - A free-radical-mediated intermolecular hydroheteroarylation of simple alkenes was
      developed. Through simply mixing heteroarenes, alkenes, Fe(III), and NaBH4 at 0 
      degrees C together, a wide range of alkylated heteroarenes could be afforded in
      moderate to excellent yields within 1 h.

PMID- 29182287
TI  - Palladium-Catalyzed Direct C-H Functionalization of Indoles with the Insertion of
      Sulfur Dioxide: Synthesis of 2-Sulfonated Indoles.
AB  - A palladium-catalyzed direct C-H bond sulfonylation of indoles with the insertion
      of sulfur dioxide is achieved through a three-component reaction of 1-(pyridin-2
      yl)indoles, DABCO.(SO2)2, and aryldiazonium tetrafluoroborates under mild
      conditions. Diverse 2-sulfonated indoles are generated by using 10 mol % of
      palladium(II) bromide as the catalyst at room temperature. This synthetic
      approach is efficient by merging palladium catalysis and insertion of sulfur
      dioxide via a radical process. 2-Pyrimidinyl can be used as the directing group
      well as for the C-H bond sulfonylation. Additionally, the directing group can be
      easily removed.

PMID- 29182288
TI  - Lewis Base-Catalyzed One-Pot Cascade Sequences of O-Alkenyl-Substituted
      Cyanohydrins: Diastereoselective Synthesis of Multisubstituted Dihydrofurans.
AB  - The first example of the diastereoselective construction of polysubstituted 2,3
      dihydrofurans incorporating contiguous quaternary and tertiary carbon centers via
      a Lewis base-catalyzed one-pot cascade sequence is described. The diversity and
      complexity of the final products can be efficiently constructed with high
      diastereoselectivities via this catalytic multistep process under mild reaction
      conditions.

PMID- 29182289
TI  - Bismuth Triflate-Catalyzed Vinylogous Nucleophilic 1,6-Conjugate Addition of para
      Quinone Methides with 3-Propenyl-2-silyloxyindoles.
AB  - A highly diastereoselective vinylogous nucleophilic 1,6-conjugate addition
      reaction of para-quinone methides with 3-propenyl-2-silyloxyindoles by a bismuth
      triflate catalyst has been developed. A number of diphenylmethane type compounds
      functionalized with oxindole motifs was obtained with excellent yields (up to
      99%) and very good diastereoselectivities (up to Z/E > 99:1).

PMID- 29182290
TI  - Oxamidation of Unsaturated O-Alkyl Hydroxamates: Synthesis of the Madangamine
      Diazatricylic (ABC Rings) Skeleton.
AB  - A novel approach to the diazatricyclic madangamine ABC ring system and the
      synthesis of an advanced, differentially protected intermediate for the synthesis
      of madangamine D is reported. Central to the success of this approach is the
      iodine(III)-mediated intramolecular oxamidation of an unsaturated O-methyl
      hydroxamate, a pi-N+-type cyclization which proceeds in high yield and with
      complete regioselectivity to generate the 2-azabicyclo[3.3.1]nonane (morphan)
      system encompassing rings A and C.

PMID- 29182291
TI  - Ru/Ni Dual Catalytic Desulfinative Photoredox Csp2-Csp3 Cross-Coupling of Alkyl
      Sulfinate Salts and Aryl Halides.
AB  - A mild Ru/Ni dual catalytic desulfinative photoredox Csp2-Csp3 cross-coupling
      reaction of alkyl sulfinate salts with aryl halides has been developed. The
      optimized catalyst system, consisting of Ru(bpy)3Cl2, Ni(COD)2, and DBU, smoothly
      mediates the coupling of a diverse set of secondary and primary nonactivated
      alkyl sulfinate salts with a broad range of electron-deficient aryl bromides,
      electron-rich aryl iodides, and heteroaryl bromides under irradiation with blue
      light. The procedure is ideal for late-stage introduction of alkyl groups on
      pharmaceutical intermediates, and the Csp2-Csp3 cross-coupling reaction allowed
      the rapid synthesis of caseine kinase 1delta inhibitor analogues via a parallel
      medicinal chemistry effort.

PMID- 29182292
TI  - Ultrasensitive Ethene Detector Based on a Graphene-Copper(I) Hybrid Material.
AB  - Ethene is a highly diffusive and relatively unreactive gas that induces aging
      responses in plants in concentrations as low as parts per billion. Monitoring
      concentrations of ethene is critically important for transport and storage of
      food crops, necessitating the development of a new generation of ultrasensitive
      detectors. Here we show that by functionalizing graphene with copper complexes
      biologically relevant concentrations of ethene and of the spoilage marker ethanol
      can be detected. Importantly, in addition these sensors provide us with important
      insights into the interactions between molecules, a key concept in chemistry.
      Chemically induced dipole fluctuations in molecules as they undergo a chemical
      reaction are harvested in an elegant way through subtle field effects in
      graphene. By exploiting changes in the dipole moments of molecules that occur
      upon a chemical reaction we are able to track the reaction and provide
      mechanistic insight that was, until now, out of reach.

PMID- 29182293
TI  - Oxidative Dehomologation of Aldehydes with Oxygen as a Terminal Oxidant.
AB  - A mild, efficient protocol for oxidative cleavage of C-C bonds in aldehydes has
      been developed that employs alkali metal hydrides as reagents and oxygen from air
      as a terminal oxidant. The method is applicable to a broad substrate range.

PMID- 29182294
TI  - Straightforward Integration Flow of a Silicon-Containing Block Copolymer for Line
      Space Patterning.
AB  - A promising alternative for the next-generation lithography is based on the
      directed self-assembly of block copolymers (BCPs) used as a bottom-up tool for
      the definition of nanometric features. Herein, a straightforward integration flow
      for line-space patterning is reported for a silicon BCP system, that is, poly(1,1
      dimethylsilacyclobutane)-b-poly(styrene) (PDMSB-b-PS), able to define sub 15 nm
      features. Both in-plane cylindrical (L0 = 20.7 nm) and out-of-plane lamellar
      structures (L0 = 23.2 nm) formed through a rapid thermal annealing-10 min at 180 
      degrees C-were successfully integrated using graphoepitaxy to provide a long
      range ordering of the BCP structure without the use of underlayers or top coats.
      Subsequent deep transfer into the silicon substrate using the hardened oxidized
      PDMSB domains as a mask is demonstrated. Combining a rapid self-assembly
      behavior, straightforward integration, and an excellent etching contrast, PDMSB-b
      PS may become a material of choice for the next-generation lithography.

PMID- 29182295
TI  - Superlight, Mechanically Flexible, Thermally Superinsulating, and Antifrosting
      Anisotropic Nanocomposite Foam Based on Hierarchical Graphene Oxide Assembly.
AB  - Lightweight, high-performance, thermally insulating, and antifrosting porous
      materials are in increasing demand to improve energy efficiency in many fields,
      such as aerospace and wearable devices. However, traditional thermally insulating
      materials (porous ceramics, polymer-based sponges) could not simultaneously meet
      these demands. Here, we propose a hierarchical assembly strategy for producing
      nanocomposite foams with lightweight, mechanically flexible, superinsulating, and
      antifrosting properties. The nanocomposite foams consist of a highly anisotropic
      reduced graphene oxide/polyimide (abbreviated as rGO/PI) network and hollow
      graphene oxide microspheres. The hierarchical nanocomposite foams are ultralight
      (density of 9.2 mg.cm-3) and exhibit ultralow thermal conductivity of 9 mW.m-1.K
      1, which is about a third that of traditional polymer-based insulating materials.
      Meanwhile, the nanocomposite foams show excellent icephobic performance. Our
      results show that hierarchical nanocomposite foams have promising applications in
      aerospace, wearable devices, refrigerators, and liquid nitrogen/oxygen
      transportation.

PMID- 29182296
TI  - Insight into the Origin of Capacity Fluctuation of Na2Ti6O13 Anode in Sodium Ion
      Batteries.
AB  - The capacity fluctuation phenomenon during cycling, which is closely related with
      solid electrolyte interphase and plays a key role for the design for advanced
      electrode, could be frequently observed in the titanium-based anode. However, the
      underlying reason for capacity fluctuation still remains unclear with rare
      related reports. Here, the origin of capacity fluctuation is verified with a long
      life Na2Ti6O13 anode. The reaction mechanism, structural evolution and reaction
      kinetics during the reported sodiation/desodiation processes were carefully
      investigated. The gradually enhanced diffusion controlled contribution resulted
      in the capacity increasing. And the capacity decay could be ascribed to the
      irreversible reaction of metallic titanium formation and the increasing potential
      polarization. It is worth noting that sodium ions seem to partially reduce NTO to
      metallic state, which is irreversible. The present study can provide more
      information for the design of advanced Na2Ti6O13 anode.

PMID- 29182297
TI  - Curious Case of Positive Current Collectors: Corrosion and Passivation at High
      Temperature.
AB  - In the evaluation of compatibility of different components of cell for high
      energy and extreme-conditions applications, the highly focused are positive and
      negative electrodes and their interaction with electrolyte. However, for high
      temperature application, the other components are also of significant influence
      and contribute toward the total health of battery. In present study, we have
      investigated the behavior of aluminum, the most common current collector for
      positive electrode materials for its electrochemical and temperature stability.
      For electrochemical stability, different electrolytes, organic and room
      temperature ionic liquids with varying Li salts (LiTFSI, LiFSI), are
      investigated. The combination of electrochemical and spectroscopic investigations
      reflects the varying mechanism of passivation at room and high temperature, as
      different compositions of decomposed complexes are found at the surface of
      metals.

PMID- 29182298
TI  - Controlling the Uptake and Regulating the Release of Nitric Oxide in Microporous
      Solids.
AB  - Representative compounds from three classes of microporous solids, namely, metal
      organic frameworks (MOFs), hybrid ultra-microporous materials (HUMs), and porous
      organic polymers (POPs), were investigated for their nitric oxide gas uptake and
      release behavior. Low-pressure sorption studies indicated strong chemisorption of
      NO on the free amine groups decorating the MOF UiO-66-NH2 when compared to its
      non-amine-functionalized parent. The HUMs demonstrated reversible physisorption
      within the low-pressure regime, but interestingly in one case there was evidence
      for chemisorption following pressurization with NO at 10 bar. Significant release
      of chemisorbed NO from the UiO-66-NH2 and one of the HUMs was triggered by
      addition of acid to the medium, a pH change from 7.4 to 5.4 being sufficient to
      trigger NO release. An imidazole-based POP exhibited chemisorption of NO at high
      pressure wherein the ring basicity facilitated both NO uptake and spontaneous
      release upon contact with the aqueous release medium.

PMID- 29182299
TI  - Switchable Conductive MOF-Nanocarbon Composite Coatings as Threshold Sensing
      Architectures.
AB  - Switchable metal-organic frameworks (MOFs) showing pronounced and stepwise volume
      changes as a response toward external stimuli such as partial pressure changes
      were integrated into electron conductive composites to generate novel threshold
      sensors with pronounced resistivity changes when approaching a critical partial
      pressure. Two "gate pressure" MOFs (DUT-8(Ni), DUT = Dresden University of
      Technology, and ELM-11, ELM = Elastic Layer-structured MOF) and one "breathing"
      MOF (MIL-53(Al), MIL = Material Institute Lavoisier) are shown to cover a wide
      range of detectable gas concentrations (~20-80%) using this concept. The highest
      resistance change is observed for composites containing a percolating carbon
      nanoparticle network (slightly above the percolation threshold concentration).
      The volume change of the MOF particles disrupts the percolating network,
      resulting in a colossal resistance change up to 7500%. Repeated threshold
      detection is particularly feasible using MIL-53(Al) due to its high mechanical
      and chemical stability, even enabling application of the composite sensor concept
      in ambient environment for the detection of volatile organic compounds at high
      concentration levels.

PMID- 29182300
TI  - CO2-Switchable Membranes Prepared by Immobilization of CO2-Breathing Microgels.
AB  - Herein, we report the development of a novel CO2-responsive membrane system
      through immobilization of CO2-responsive microgels into commercially available
      microfiltration membranes using a method of dynamic adsorption. The microgels,
      prepared from soap-free emulsion polymerization of CO2-responsive monomer 2
      (diethylamino)ethyl methacrylate (DEA), can be reversibly expanded and shrunken
      upon CO2/N2 alternation. When incorporated into the membranes, this switching
      behavior was preserved and further led to transformation between microfiltration
      and ultrafiltration membranes, as indicated from the dramatic changes on water
      flux and BSA rejection results. This CO2-regulated performance switching of
      membranes was caused by the changes of water transportation channel, as revealed
      from the dynamic water contact angle tests and SEM observation. This work
      represents a simple yet versatile strategy for making CO2-responsive membranes.

PMID- 29182301
TI  - Electropolymerization Porous Aromatic Framework Film As a Hole-Transport Layer
      for Inverted Perovskite Solar Cells with Superior Stability.
AB  - PAF-86 film is electropolymerized (EP) by targeted monomer M1 tethered
      bifunctional carbozolyl moieties which not only serve in electron donation but
      also provide effective electrochemical (EC) active sites. The resulting PAF-86
      film possesses a fairly compact surface, remarkable stability, efficient hole
      extraction capacity, and hole-transporting materials (HTMs) for inverted
      heterojunction perovskite solar cells (PSCs). Likewise, our investigation shows
      that PAF-86 film based perovskite solar cells (PSCs) retained about 80% power
      conversion efficiency (PCE) without encapsulation in air, and poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) based PSCs devices
      reduce to 4% under the same conditions. More impressively, the
      electropolymerization approach is convenient, controlled, and operated at ambient
      conditions which elude post heat-treatments and are appropriate for industrial
      application.

PMID- 29182302
TI  - Macroscale and Nanoscale Morphology Evolution during in Situ Spray Coating of
      Titania Films for Perovskite Solar Cells.
AB  - Mesoporous titania is a cheap and widely used material for photovoltaic
      applications. To enable a large-scale fabrication and a controllable pore size,
      we combined a block copolymer-assisted sol-gel route with spray coating to
      fabricate titania films, in which the block copolymer polystyrene-block
      poly(ethylene oxide) (PS-b-PEO) is used as a structure-directing template. Both
      the macroscale and nanoscale are studied. The kinetics and thermodynamics of the
      spray deposition processes are simulated on a macroscale, which shows a good
      agreement with the large-scale morphology of the spray-coated films obtained in
      practice. On the nanoscale, the structure evolution of the titania films is
      probed with in situ grazing incidence small-angle X-ray scattering (GISAXS)
      during the spray process. The changes of the PS domain size depend not only on
      micellization but also on solvent evaporation during the spray coating.
      Perovskite (CH3NH3PbI3) solar cells (PSCs) based on sprayed titania film are
      fabricated, which showcases the suitability of spray-deposited titania films for
      PSCs.

PMID- 29182303
TI  - Spontaneous Periodic Delamination of Thin Films To Form Crack-Free Metal and
      Silicon Ribbons with High Stretchability.
AB  - Design of electronic materials with high stretchability is of great importance
      for realizing soft and conformal electronics. One strategy of realizing
      stretchable metals and semiconductors is to exploit the buckling of materials
      bonded to elastomers. However, the level of stretchability is often limited by
      the cracking and fragmentation of the materials that occurs when constrained
      buckling occurs while bonded to the substrate. Here, we exploit a failure
      mechanism, spontaneous buckling-driven periodic delamination, to achieve high
      stretchability in metal and silicon films that are deposited on prestrained
      elastomer substrates. We find that both globally periodic buckle-delaminated
      pattern and ordered cracking patterns over large areas are observed in the
      spontaneously buckle-delaminated thin films. The geometry of periodic delaminated
      buckles and cracking periodicity can be predicted by theoretical models. By
      patterning the films into ribbons with widths smaller than the predicted cracking
      periodicity, we demonstrate the design of crack-free and spontaneous delaminated
      ribbons on highly prestrained elastomer substrates, which provides a high
      stretchability of about 120% and 400% in Si and Au ribbons, respectively. We find
      that the high stretchability is mainly attributed to the largely relaxed strain
      in the ribbons via spontaneous buckling-driven delamination, as made evident by
      the small maximum tensile strain in both ribbons, which is measured to be over
      100 times smaller than that of the substrate prestrain.

PMID- 29182304
TI  - Lightweight, Mesoporous, and Highly Absorptive All-Nanofiber Aerogel for
      Efficient Solar Steam Generation.
AB  - The global fresh water shortage has driven enormous endeavors in seawater
      desalination and wastewater purification; among these, solar steam generation is
      effective in extracting fresh water by efficient utilization of naturally
      abundant solar energy. For solar steam generation, the primary focus is to design
      new materials that are biodegradable, sustainable, of low cost, and have high
      solar steam generation efficiency. Here, we designed a bilayer aerogel structure
      employing naturally abundant cellulose nanofibrils (CNFs) as basic building
      blocks to achieve sustainability and biodegradability as well as employing a
      carbon nanotube (CNT) layer for efficient solar utilization with over 97.5% of
      light absorbance from 300 to 1200 nm wavelength. The ultralow density (0.0096
      g/cm3) of the aerogel ensures that minimal material is required, reducing the
      production cost while at the same time satisfying the water transport and thermal
      insulation requirements due to its highly porous structure (99.4% porosity).
      Owing to its rationally designed structure and thermal-regulation performance,
      the bilayer CNF-CNT aerogel exhibits a high solar-energy conversion efficiency of
      76.3% and 1.11 kg m-2 h-1 at 1 kW m-2 (1 Sun) solar irradiation, comparable or
      even higher than most of the reported solar steam generation devices. Therefore,
      the all-nanofiber aerogel presents a new route for designing biodegradable,
      sustainable, and scalable solar steam generation devices with superb performance.

PMID- 29182305
TI  - Point-of-Use Nanobiosensor for Detection of Dengue Virus NS1 Antigen in Adult
      Aedes aegypti: A Potential Tool for Improved Dengue Surveillance.
AB  - Dengue virus (DENV) and its primary mosquito vectors Aedes spp. have spread to
      every continent except Antarctica, causing outbreaks and autochthonous
      transmission in previously disease-free regions. Recently, the spread of other
      arboviruses carried by invasive Aedes spp., such as Chikungunya and Zika, seem to
      be following similar trends as DENV and have renewed interest in monitoring and
      modeling arboviruses within mosquito vectors. Unfortunately, current commercially
      available detection methods are designed for the diagnosis of DENV in humans or
      are too expensive and complex for sustainable monitoring. We report a novel
      electronic nanobiosensor utilizing a single-walled carbon nanotube networks
      chemiresistor transducer functionalized with antidengue NS1 monoclonal antibodies
      for rapid detection of the dengue nonstructural protein 1 (NS1). NS1 is a highly
      conserved protein secreted at high concentrations during viral replication and is
      a biomarker for DENV infection. NS1 was successfully detected in spiked adult
      Aedes aegypti homogenate over a broad dynamic range with high sensitivity and
      selectivity. The biosensor is compatible with "gold-standard" adult mosquito
      field-collection protocols and generates electronic data that can be readily
      stored or wirelessly transmitted. Thus, it has potential for remote and real-time
      monitoring of wild mosquito populations.

PMID- 29182306
TI  - Imaging Ca2+ with a Fluorescent Rhodol.
AB  - Ca2+ mediates a host of biochemical and biophysical signaling processes in cells.
      The development of synthetic, Ca2+-sensitive fluorophores has played an
      instrumental role in our understanding of the temporal and spatial dynamics of
      Ca2+. Coupling Ca2+-selective ligands to fluorescent reporters has provided a
      wealth of excellent indicators that span the visible excitation and emission
      spectrum and possess Ca2+ affinities suited to a variety of cellular contexts.
      One underdeveloped area is the use of hybrid rhodamine/fluorescein fluorophores,
      or rhodols, in the context of Ca2+ sensing. Rhodols are bright and photostable
      and have good two-photon absorption cross sections (sigmaTPA), making them
      excellent candidates for incorporation into Ca2+-sensing scaffolds. Here, we
      present the design, synthesis, and application of rhodol Ca2+ sensor 1 (RCS-1), a
      chlorinated pyrrolidine-based rhodol. RCS-1 possesses a Ca2+ binding constant of
      240 nM and a 10-fold turn response to Ca2+. RCS-1 effectively absorbs infrared
      light and has a sigmaTPA of 76 GM at 840 nm, 3-fold greater than that of its
      fluorescein-based counterpart. The acetoxy-methyl ester of RCS-1 stains the
      cytosol of live cells, enabling observation of Ca2+ fluctuations and cultured
      neurons using both one- and two-photon illumination. Together, these results
      demonstrate the utility of rhodol-based scaffolds for Ca2+ sensing using two
      photon illumination in neurons.

PMID- 29182307
TI  - Model Study To Assess Softwood Hemicellulose Hydrolysates as the Carbon Source
      for PHB Production in Paraburkholderia sacchari IPT 101.
AB  - Softwood hemicellulose hydrolysates are a cheap source of sugars that can be used
      as a feedstock to produce polyhydroxybutyrates (PHB), which are biobased and
      compostable bacterial polyesters. To assess the potential of the hemicellulosic
      sugars as a carbon source for PHB production, synthetic media containing softwood
      hemicellulose sugars (glucose, mannose, galactose, xylose, arabinose) and the
      potentially inhibitory lignocellulose degradation products (acetic acid, 5
      hydroxymethylfurfural (HMF), furfural, and vanillin) were fermented with the
      model strain Paraburkholderia sacchari IPT 101. Relative to pure glucose,
      individual fermentation for 24 h with 20 g/L mannose or galactose exhibited
      maximum specific growth rates of 97% and 60%, respectively. On the other hand,
      with sugar mixtures of glucose, mannose, galactose, xylose, and arabinose, the
      strain converted all sugars simultaneously to reach a maximum PHB concentration
      of 5.72 g/L and 80.5% PHB after 51 h. The addition of the inhibitor mixture at
      the following concentration, sodium acetate (2.11 g/L), HMF (0.67 g/L), furfural
      (0.66 g/L), and vanillin (0.93 g/L), to the sugar mixture stopped the growth
      entirely within 24 h. Individually, the inhibitors either had no effect or only
      reduced growth. Moreover, it was found that a bacterial inoculum with high
      initial cell density (optical density, OD >= 5.6) could overcome the growth
      inhibition to yield an OD of 13 within 24 h. Therefore, softwood hemicellulose
      sugars are viable carbon sources for PHB production. Nevertheless, real softwood
      hemicellulose hydrolysates need detoxification or a high inoculum to overcome
      inhibitory effects and allow bacterial growth.

PMID- 29182308
TI  - Targeted MultiNotch MS3 Approach for Relative Quantification of N-Glycans Using
      Multiplexed Carbonyl-Reactive Isobaric Tags.
AB  - The recently developed and commercially available carbonyl-reactive tandem mass
      tags (aminoxyTMT) enable multiplexed quantification of glycans through comparison
      of reporter ion intensities. However, challenges still exist for collision
      activated dissociation (CAD) MS/MS based quantification of aminoxyTMT due to the
      relatively low reporter ion yield especially for glycans with labile structures.
      To circumvent this limitation, we utilized the unique structural features of N
      glycan molecules, the common core sugar sequence (HexNAc)2(Man)3, and common m/z
      of Yn ions generated from different types of precursors by MS/MS and designed a
      Y1 ion triggered, targeted MultiNotch MS3 relative quantification approach based
      on aminoxyTMT labeling. This approach was implemented on a nanoHILIC-Tribrid
      quadrupole-ion trap-Orbitrap platform, which enables prescreening of aminoxyTMT
      labeled N-glycan precursor ions by Y1 ion fragment ion mass in a higher-energy
      collisional dissociation (HCD) MS/MS scan and coisolation and cofragmentation of
      multiple Yn fragment ions that carry the isobaric tags from the inclusion list in
      the MS/MS/MS scan. Through systematical optimization and evaluation using N
      glycans released from several glycoprotein standards and human serum proteins, we
      demonstrated that the Y1 ion triggered, targeted MultiNotch MS3 approach offers
      improved accuracy, precision, and sensitivity for relative quantification
      compared to traditional data-dependent MS2 and Y1 ion MS3 quantification methods.

PMID- 29182310
TI  - Enzyme-Mimetic Antioxidant Luminescent Nanoparticles for Highly Sensitive
      Hydrogen Peroxide Biosensing.
AB  - Hydrogen peroxide (H2O2) is an abundant molecule associated with biological
      functions and reacts with natural enzymes, such as catalase. Even though direct
      H2O2 measurement can be used to diagnose pathological conditions, such as
      infection and inflammation, H2O2 quantification further enables the detection of
      disease biomarkers in enzyme-linked assays (e.g., ELISA) in which enzymatic
      reactions may generate or consume H2O2. Such a quantification is often measured
      optically with organic dyes in biological media that suffer, however, from poor
      stability. Currently, the optical H2O2 biosensing without organic-dyes in
      biological media and at low, submicromolar, concentrations has yet to be
      achieved. Herein, we rationally design biomimetic artificial enzymes based on
      antioxidant CeO2 nanoparticles that become luminescent upon their Eu3+ doping. We
      vary systematically their diameter from 4 to 16 nm and study their catalase
      mimetic antioxidant activity, manifested as catalytic H2O2 decomposition in
      aqueous solutions, revealing a strong nanoparticle surface area dependency. The
      interaction with H2O2 influences distinctly the particle luminescence rendering
      them highly sensitive H2O2 biosensors down to 0.15 MUM (5.2 ppb) in solutions for
      biological assays. Our results link two, so far, unrelated research domains, the
      CeO2 nanoparticle antioxidant activity and luminescence by rare-earth doping.
      When these enzyme-mimetic nanoparticles are coupled with alcohol oxidase,
      biosensing can be extended to ethanol exemplifying how their detection potential
      can be broadened to additional biologically relevant metabolites. The enzyme
      mimetic nanomaterial developed here could serve as a starting point of
      sophisticated in vitro assays toward the highly sensitive detection of disease
      biomarkers.

PMID- 29182312
TI  - Potentially Immunogenic Contaminants in Wood-Based and Bacterial Nanocellulose:
      Assessment of Endotoxin and (1,3)-beta-d-Glucan Levels.
AB  - Knowledge gaps in the biosafety data of the nanocellulose (NC) for biomedical use
      through various routes of administration call for closer look at health and
      exposure evaluation. This work evaluated the potentially immunogenic contaminants
      levels, for example, endotoxin and (1,3)-beta-d-glucan, in four representative
      NCs, that is, wood-based NCs and bacterial cellulose (BC). The hot-water extracts
      were analyzed with ELISA assays, HPSEC-MALLS, GC, and NMR analysis. Varying
      levels of endotoxin and (1,3)-beta-d-glucan contaminats were found in these
      widely used NCs. Although the beta-(1,3)-d-glucan was not detected from the NMR
      spectra due to the small extract samples amount (2-7 mg), the anomerics and
      highly diastereotopic 6-CH2 signals may suggest the presence of beta-(1,4)
      linkages with beta-(1,6) branching in the polysaccharides of NCs' hot-water
      extracts, which were otherwise not detectable in the enzymatic assay. In all, the
      article highlights the importance of monitoring various water-soluble potentially
      immunogenic contaminants in NC for biomedical use.

PMID- 29182309
TI  - Fast-Scan Cyclic Voltammetry: Chemical Sensing in the Brain and Beyond.

PMID- 29182311
TI  - Polymyxin-Induced Lipid A Deacylation in Pseudomonas aeruginosa Perturbs
      Polymyxin Penetration and Confers High-Level Resistance.
AB  - Polymyxins are last-line antibiotics against life-threatening multidrug-resistant
      Gram-negative bacteria. Unfortunately, polymyxin resistance is increasingly
      reported, leaving a total lack of therapies. Using lipidomics and
      transcriptomics, we discovered that polymyxin B induced lipid A deacylation via
      pagL in both polymyxin-resistant and -susceptible Pseudomonas aeruginosa. Our
      results demonstrated that the deacylation of lipid A is an "innate immunity"
      response to polymyxins and a key compensatory mechanism to the aminoarabinose
      modification to confer high-level polymyxin resistance in P. aeruginosa.
      Furthermore, cutting-edge neutron reflectometry studies revealed that an
      assembled outer membrane (OM) with the less hydrophobic penta-acylated lipid A
      decreased polymyxin B penetration, compared to the hexa-acylated form. Polymyxin
      analogues with enhanced hydrophobicity displayed superior penetration into the
      tail regions of the penta-acylated lipid A OM. Our findings reveal a previously
      undiscovered mechanism of polymyxin resistance, wherein polymyxin-induced lipid A
      remodeling affects the OM packing and hydrophobicity, perturbs polymyxin
      penetration, and thereby confers high-level resistance.

PMID- 29182313
TI  - Biocatalytically Active Thin Films via Self-Assembly of 2-Deoxy-d-ribose-5
      phosphate Aldolase-Poly(N-isopropylacrylamide) Conjugates.
AB  - 2-Deoxy-d-ribose-5-phosphate aldolase (DERA) is a biocatalyst that is capable of
      converting acetaldehyde and a second aldehyde as acceptor into enantiomerically
      pure mono- and diyhydroxyaldehydes, which are important structural motifs in a
      number of pharmaceutically active compounds. However, substrate as well as
      product inhibition requires a more-sophisticated process design for the synthesis
      of these motifs. One way to do so is to the couple aldehyde conversion with
      transport processes, which, in turn, would require an immobilization of the
      enzyme within a thin film that can be deposited on a membrane support.
      Consequently, we developed a fabrication process for such films that is based on
      the formation of DERA-poly(N-isopropylacrylamide) conjugates that are
      subsequently allowed to self-assemble at an air-water interface to yield the
      respective film. In this contribution, we discuss the conjugation conditions,
      investigate the interfacial properties of the conjugates, and, finally,
      demonstrate a successful film formation under the preservation of enzymatic
      activity.

PMID- 29182314
TI  - Mesoporous TiO2 Embedded with a Uniform Distribution of CuO Exhibit Enhanced
      Charge Separation and Photocatalytic Efficiency.
AB  - Mixed metal oxide nanoparticles have interesting physical and chemical
      properties, but synthesizing them with colloidal methods is still challenging and
      often results in very heterogeneous structures. Here, we describe a simple method
      to synthesize mesoporous titania nanoparticles implanted with a uniform
      distribution of copper oxide nanocrystals (CuO@MTs). By calcining a titanium
      based metal-organic framework (MIL-125) in the presence of Cu ions, we can trap
      the Cu in the TiO2 matrix. Removal of the organic ligand creates mesoporosity and
      limits phase separation so that tiny CuO nanocrystals form in the interstices of
      the TiO2. The CuO@MTs exhibits superior performance for photocatalytic hydrogen
      evolution (4760 MUmol h-1) that is >90 times larger than pristine titania.

PMID- 29182316
TI  - Real-Time Monitoring of Endogenous Cysteine Levels In Vivo by near-Infrared Turn
      on Fluorescent Probe with Large Stokes Shift.
AB  - Cysteine (Cys), as an important biothiol, plays a major role in many
      physiological processes like protein synthesis, detoxification and metabolism,
      and also is closely associated with a variety of diseases; thus the design of
      novel highly selective and sensitive near-infrared (NIR) fluorescent probes for
      Cys detection in vivo is of great significance. Herein, we report a selective and
      sensitive NIR turn-on fluorescent probe (CP-NIR) with large Stokes shift for
      detecting Cys in vivo. Upon addition of Cys to the solution of the probe, it is
      absorption wavelength shifts from 550 to 600 nm, accompanying with an obvious
      enhancement of NIR fluorescence emission centering around 760 nm. This Michael
      addition reaction-based probe shows a large Stokes shift (160 nm), low detection
      limit (48 nM), fast response time, and low toxicity. Moreover, this novel NIR
      probe with good cell permeability was successfully applied to monitoring
      endogenous Cys in living cells and in a mouse model.

PMID- 29182315
TI  - Determinants and Prediction of Esterase Substrate Promiscuity Patterns.
AB  - Esterases receive special attention because of their wide distribution in
      biological systems and environments and their importance for physiology and
      chemical synthesis. The prediction of esterases' substrate promiscuity level from
      sequence data and the molecular reasons why certain such enzymes are more
      promiscuous than others remain to be elucidated. This limits the surveillance of
      the sequence space for esterases potentially leading to new versatile
      biocatalysts and new insights into their role in cellular function. Here, we
      performed an extensive analysis of the substrate spectra of 145 phylogenetically
      and environmentally diverse microbial esterases, when tested with 96 diverse
      esters. We determined the primary factors shaping their substrate range by
      analyzing substrate range patterns in combination with structural analysis and
      protein-ligand simulations. We found a structural parameter that helps rank
      (classify) the promiscuity level of esterases from sequence data at 94% accuracy.
      This parameter, the active site effective volume, exemplifies the topology of the
      catalytic environment by measuring the active site cavity volume corrected by the
      relative solvent accessible surface area (SASA) of the catalytic triad. Sequences
      encoding esterases with active site effective volumes (cavity volume/SASA) above
      a threshold show greater substrate spectra, which can be further extended in
      combination with phylogenetic data. This measure provides also a valuable tool
      for interrogating substrates capable of being converted. This measure, found to
      be transferred to phosphatases of the haloalkanoic acid dehalogenase superfamily
      and possibly other enzymatic systems, represents a powerful tool for low-cost
      bioprospecting for esterases with broad substrate ranges, in large scale sequence
      data sets.

PMID- 29182317
TI  - Twists and Turns of Orbiting and Spinning Metallic Microparticles Powered by
      Megahertz Ultrasound.
AB  - Micromotors powered by megahertz ultrasound, first reported about 5 years ago,
      have lately been considered a promising platform for a wide range of microscale
      applications, yet we are only at the early stage of understanding their operating
      mechanisms. Through carefully designed experiments, and by comparing the results
      to acoustic theories, we present here an in-depth study of the behaviors of
      particles activated by ultrasound, especially their in-plane orbiting and
      spinning dynamics. Experiments suggest that metallic microrods orbit in tight
      circles near the resonance ultrasound frequency, likely driven by localized
      acoustic streaming due to slightly bent particle shapes. On the other hand,
      particle spins around their long axes on nodal lines, where phase-mismatched
      orthogonal sound waves possibly produce a viscous torque. Intriguingly, such a
      torque spins metal-dielectric Janus microspheres back and forth in an unusual
      "rocking chair" fashion. Overall, our observations and analysis provide fresh and
      much needed insights on the interesting particle dynamics in resonating
      ultrasound and could help with developing more powerful and controllable
      micromachines with biocompatible energy sources.

PMID- 29182318
TI  - Heterochiral DNA Strand-Displacement Circuits.
AB  - The absence of a straightforward strategy to interface native d-DNA with its
      enantiomer l-DNA-oligonucleotides of opposite chirality are incapable of forming
      contiguous Watson-Crick base pairs with each other-has enforced a "homochiral"
      paradigm over the field of dynamic DNA nanotechnology. As a result, chirality, a
      key intrinsic property of nucleic acids, is often overlooked as a design element
      for engineering of DNA-based devices, potentially limiting the types of behaviors
      that can be achieved using these systems. Here we introduce a toehold-mediated
      strand-displacement methodology for transferring information between orthogonal
      DNA enantiomers via an achiral intermediary, opening the door for "heterochiral"
      DNA nanotechnology having fully interfaced d-DNA and l-DNA components. Using this
      approach, we demonstrate several heterochiral DNA circuits having novel
      capabilities, including autonomous chiral inversion of DNA sequence information
      and chirality-based computing. In addition, we show that heterochiral circuits
      can directly interface endogenous RNAs (e.g., microRNAs) with bioorthogonal l
      DNA, suggesting applications in bioengineering and nanomedicine. Overall, this
      work establishes chirality as a design parameter for engineering of dynamic DNA
      nanotechnology, thereby expanding the types of architectures and behaviors that
      can be realized using DNA.

PMID- 29182319
TI  - Relative Contribution of nirK- and nirS- Bacterial Denitrifiers as Well as Fungal
      Denitrifiers to Nitrous Oxide Production from Dairy Manure Compost.
AB  - The relative contribution of fungi, bacteria, and nirS and nirK denirifiers to
      nitrous oxide (N2O) emission with unknown isotopic signature from dairy manure
      compost was examined by selective inhibition techniques. Chloramphenicol (CHP),
      cycloheximide (CYH), and diethyl dithiocarbamate (DDTC) were used to suppress the
      activity of bacteria, fungi, and nirK-possessing denitrifiers, respectively.
      Produced N2O were surveyed to isotopocule analysis, and its 15N site preference
      (SP) and delta18O values were compared. Bacteria, fungi, nirS, and nirK gene
      abundances were compared by qPCR. The results showed that N2O production was
      strongly inhibited by CHP addition in surface pile samples (82.2%) as well as in
      nitrite-amended core samples (98.4%), while CYH addition did not inhibit the N2O
      production. N2O with unknown isotopic signature (SP = 15.3-16.20/00), accompanied
      by delta18O (19.0-26.80/00) values which were close to bacterial denitrification,
      was also suppressed by CHP and DDTC addition (95.3%) indicating that nirK
      denitrifiers were responsible for this N2O production despite being less abundant
      than nirS denitrifiers. Altogether, our results suggest that bacteria are
      important for N2O production with different SP values both from compost surface
      and pile core. However, further work is required to decipher whether N2O with
      unknown isotopic signature is mostly due to nirK denitrifiers that are
      taxonomically different from the SP-characterized strains and therefore have
      different SP values rather than also being interwoven with the contribution of
      the NO-detoxifying pathway and/or of co-denitrification.

PMID- 29182320
TI  - Large-Scale Computation of Nuclear Magnetic Resonance Shifts for Paramagnetic
      Solids Using CP2K.
AB  - Large-scale computations of nuclear magnetic resonance (NMR) shifts for extended
      paramagnetic solids (pNMR) are reported using the highly efficient Gaussian
      augmented plane-wave implementation of the CP2K code. Combining hyperfine
      couplings obtained with hybrid functionals with g-tensors and orbital shieldings
      computed using gradient-corrected functionals, contact, pseudocontact, and
      orbital-shift contributions to pNMR shifts are accessible. Due to the efficient
      and highly parallel performance of CP2K, a wide variety of materials with large
      unit cells can be studied with extended Gaussian basis sets. Validation of
      various approaches for the different contributions to pNMR shifts is done first
      for molecules in a large supercell in comparison with typical quantum-chemical
      codes. This is then extended to a detailed study of g-tensors for extended solid
      transition-metal fluorides and for a series of complex lithium vanadium
      phosphates. Finally, lithium pNMR shifts are computed for Li3V2(PO4)3, for which
      detailed experimental data are available. This has allowed an in-depth study of
      different approaches (e.g., full periodic versus incremental cluster computations
      of g-tensors and different functionals and basis sets for hyperfine computations)
      as well as a thorough analysis of the different contributions to the pNMR shifts.
      This study paves the way for a more-widespread computational treatment of NMR
      shifts for paramagnetic materials.

PMID- 29182321
TI  - Macrocycle Conformational Sampling by DFT-D3/COSMO-RS Methodology.
AB  - : To find and calibrate a robust and reliable computational protocol for mapping
      conformational space of medium-sized molecules, exhaustive conformational
      sampling has been carried out for a series of seven macrocyclic compounds of
      varying ring size and one acyclic analogue. While five of them were taken from
      the MD/LLMOD/force field study by Shelley and co-workers ( Watts , K. S. ; Dalal
      , P. ; Tebben , A. J. ; Cheney , D. L. ; Shelley , J. C. Macrocycle
      Conformational Sampling with MacroModel . J. Chem. Inf. MODEL: 2014 , 54 , 2680 -
      2696 ), three represent potential macrocyclic inhibitors of human cyclophilin A.
      The free energy values (GDFT/COSMO-RS) for all of the conformers of each compound
      were obtained by a composite protocol based on in vacuo quantum mechanics (DFT-D3
      method in a large basis set), standard gas-phase thermodynamics, and the COSMO-RS
      solvation model. The GDFT/COSMO-RS values were used as the reference for
      evaluating the performance of conformational sampling algorithms: standard and
      extended MD/LLMOD search (simulated-annealing molecular dynamics with low-lying
      eigenvector following algorithms, employing the OPLS2005 force field plus GBSA
      solvation) available in MacroModel and plain molecular dynamics (MD) sampling at
      high temperature (1000 K) using the semiempirical quantum mechanics (SQM)
      potential SQM(PM6-D3H4/COSMO) followed by energy minimization of the snapshots.
      It has been shown that the former protocol (MD/LLMOD) may provide a more complete
      set of initial structures that ultimately leads to the identification of a
      greater number of low-energy conformers (as assessed by GDFT/COSMO-RS) than the
      latter (i.e., plain SQM MD). The CPU time needed to fully evaluate one medium
      sized compound (~100 atoms, typically resulting in several hundred or a few
      thousand conformers generated and treated quantum-mechanically) is approximately
      1,000-100,000 CPU hours on today's computers, which transforms to 1-7 days on a
      small-sized computer cluster with a few hundred CPUs. Finally, our data sets
      based on the rigorous quantum-chemical approach allow us to formulate a composite
      conformational sampling protocol with multiple checkpoints and truncation of
      redundant structural data that offers superior insights at affordable
      computational cost.

PMID- 29182322
TI  - Controlling Photochemistry via Isotopomers and IR Pre-excitation.
AB  - It is a photochemist's dream to be able to photoinduce a reaction of a specific
      molecular species in an ensemble of similar but not identical ones. The problem
      is that similar molecules often exhibit nearly identical UV-Vis absorption
      spectra, making them difficult or impossible to distinguish or to select
      spectroscopically. The ultrafast VIPER (VIbrationally Promoted Electronic
      Resonance) pulse sequence allows to pick a single species for electronic
      excitation based on its infrared spectrum. The latter usually shows more
      features, allowing the discrimination between species than the UV-Vis spectrum.
      Here, we show that it is possible to induce and monitor species-selective
      photochemistry even for molecules with virtually identical UV-Vis spectra, which
      is the case for isotopomers. Next to isotope-selective photochemistry in
      solution, applications to orthogonal photo-uncaging and species-selective
      spectroscopy and photochemistry in mixtures are within reach.

PMID- 29182324
TI  - Protein-Ligand Dissociation Simulated by Parallel Cascade Selection Molecular
      Dynamics.
AB  - We investigated the dissociation process of tri-N-acetyl-d-glucosamine from hen
      egg white lysozyme using parallel cascade selection molecular dynamics (PaCS-MD),
      which comprises cycles of multiple unbiased MD simulations using a selection of
      MD snapshots as the initial structures for the next cycle. Dissociation was
      significantly accelerated by PaCS-MD, in which the probability of rare event
      occurrence toward dissociation was enhanced by the selection and rerandomization
      of the initial velocities. Although this complex was stable during 1 MUs of
      conventional MD, PaCS-MD easily induced dissociation within 100-101 ns. We found
      that velocity rerandomization enhances the dissociation of triNAG from the bound
      state, whereas diffusion plays a more important role in the unbound state. We
      calculated the dissociation free energy by analyzing all PaCS-MD trajectories
      using the Markov state model (MSM), compared the results to those obtained by
      combinations of PaCS-MD and umbrella sampling (US), steered MD (SMD) and US, and
      SMD and the Jarzynski equality, and experimentally determined binding free
      energy. PaCS-MD/MSM yielded results most comparable to the experimentally
      determined binding free energy, independent of simulation parameter variations,
      and also gave the lowest standard errors.

PMID- 29182323
TI  - Demystifying P2Y1 Receptor Ligand Recognition through Docking and Molecular
      Dynamics Analyses.
AB  - We performed a molecular modeling analysis of 100 nucleotide-like bisphosphates
      and 46 non-nucleotide arylurea derivatives previously reported as P2Y1R binders
      using the recently solved hP2Y1R structures. We initially docked the compounds at
      the X-ray structures and identified the binding modes of representative compounds
      highlighting key patterns in the structure-activity relationship (SAR). We
      subsequently subjected receptor complexes with selected key agonists (2MeSADP and
      MRS2268) and antagonists (MRS2500 and BPTU) to membrane molecular dynamics (MD)
      simulations (at least 200 ns run in triplicate, simulation time 0.6-1.6 MUs per
      ligand system) while considering alternative protonation states of nucleotides.
      Comparing the temporal evolution of the ligand-protein interaction patterns with
      available site-directed mutagenesis (SDM) data and P2Y1R apo state simulation
      provided further SAR insights and suggested reasonable explanations for loss/gain
      of binding affinity as well as the most relevant charged species for nucleotide
      ligands. The MD analysis also predicted local conformational changes required for
      the receptor inactive state to accommodate nucleotide agonists.

PMID- 29182325
TI  - Switching on a Spin Glass: Flux Growth, Structure, and Magnetism of La11Mn13-x
      yNixAlySn4-delta Intermetallics.
AB  - Reactions of tin and manganese in a lanthanum/nickel eutectic melt in alumina
      crucibles produce La11Mn13-x-yNixAlySn4-delta (0 <= x <= 3.6; 2.5 <= y <= 4.9;
      0.6 <= delta <= 1.1) phases with the stoichiometry dependent on the reactant
      ratio. These compounds crystallize in a new tetragonal structure type in space
      group P4/mbm, with a = 8.4197(1) A, c = 19.2414(3) A, and Z = 2 for
      La11Mn8.2Ni0.8Al4Sn3.3. The structure can be viewed as an intergrowth between
      La6Co11Ga3-type layers and Cr5B3-type La/Sn slabs. This system represents a
      unique playground to study the itinerant magnetism of diluted icosahedral Mn
      layers. The dilution of manganese sites in the Mn/Ni/Al layer with nonmagnetic
      elements has a significant effect on magnetic properties, with low Mn content
      analogues being paramagnetic and higher Mn content analogues such as
      La11Mn10Al3Sn3.4 exhibiting spin-glass behavior with a freezing transition at 20
      K. The lack of long-range magnetic ordering is confirmed by heat capacity and
      resistivity measurements.

PMID- 29182326
TI  - Phase Inversion Directly Induced Tight Ultrafiltration (UF) Hollow Fiber
      Membranes for Effective Removal of Textile Dyes.
AB  - This study has demonstrated the application of tight ultrafiltration (UF)
      membranes for effective removal of textile dyes from water at a low pressure.
      Novel UF hollow fiber membranes with well-defined nanopores and surface charges
      were developed via a single-step spinning process without any post-treatment. The
      newly developed tight UF hollow fibers not only possess a small mean pore
      diameter of 1.0-1.3 nm with a molecular weight cutoff (MWCO) of 1000-2000 Da but
      also have a high pure water permeability (PWP) of 82.5-117.6 L m-2 h-1 bar-1.
      Through the synergistic effects of size exclusion and charge repulsion, the novel
      UF hollow fibers can effectively remove various dyes with impressive rejections
      of 93.2-99.9% at 1 bar. At the same time, more than 92% of inorganic salts (i.e.,
      NaCl and Na2SO4) would permeate through the fibers, reducing the detrimental
      effects of concentration polarization and providing an attracted avenue for salts
      reuse. The tight UF hollow fibers also exhibit robust performance in a continuous
      operation of 170 h or at a high feed recovery of 90%. The fouled fibers can be
      easily regenerated by backwash of water with a flux recovery of larger than 92%.
      The newly developed tight UF hollow fiber membranes display huge potential for
      treating textile wastewater and other impaired effluents because of their great
      separation performance and simple fabrication process.

PMID- 29182327
TI  - Nonredox Metal Ions Promoted Olefin Epoxidation by Iron(II) Complexes with H2O2:
      DFT Calculations Reveal Multiple Channels for Oxygen Transfer.
AB  - Nonredox metal ions play significant roles in a wide range of biological and
      chemical oxidations in which they can modulate the oxidative reactivity of those
      redox metal ions. With environmentally benign H2O2 as oxidant, the influence of
      nonredox metal ions on an iron(II) complex mediated olefin epoxidation was
      investigated through experimental studies and theoretical calculations. It was
      found that adding nonredox metal ions like Sc3+ can substantially improve the
      oxygen transfer efficiency of the iron(II) complex toward cyclooctene epoxidation
      even in the presence of certain amount of water. In 18O-labeling experiments with
      18O water, the presence of Sc3+ provided a higher 18O incorporation in epoxide.
      In UV-vis studies, it was found that the presence of Sc3+ makes both FeIII-OOH
      and FeIV?O species unstable. Density functional theory calculations further
      disclosed that, in the presence of Sc(OTf)3, the Sc3+ adducts of FeIII-OOH and
      FeIV?O species are capable of epoxidizing olefin as well as FeV?O species, thus
      opening multiple channels for oxygenation. In particular, in the pathway of
      cyclooctene epoxidation, the FeIV?O/Sc3+ adduct-mediated epoxidation is more
      energetically favorable than that of the FeV?O species (12.2 vs 17.2 kcal/mol).
      This information may implicate that the presence of certain nonredox metal ions
      can facilitate these redox metal ions mediating biological and chemical
      oxidations happening at a relatively low oxidation state, which is more
      energetically accessible.

PMID- 29182328
TI  - Copper-Catalyzed Alkylation of Aliphatic Amines Induced by Visible Light.
AB  - Although the alkylation of an amine by an alkyl halide serves as a "textbook
      example" of a nucleophilic substitution reaction, the selective mono-alkylation
      of aliphatic amines by unactivated, hindered halides persists as a largely
      unsolved challenge in organic synthesis. We report herein that primary aliphatic
      amines can be cleanly mono-alkylated by unactivated secondary alkyl iodides in
      the presence of visible light and a copper catalyst. The method operates under
      mild conditions (-10  degrees C), displays good functional-group compatibility,
      and employs commercially available catalyst components. A trapping experiment
      with TEMPO is consistent with C-N bond formation via an alkyl radical in an out
      of-cage process.

PMID- 29182329
TI  - Simple Closed-Form Expression for Penning Reaction Rate Coefficients for Cold
      Molecular Collisions by Non-Hermitian Time-Independent Adiabatic Scattering
      Theory.
AB  - We present a simple expression and its derivation for reaction rate coefficients
      for cold anisotropic collision experiments based on adiabatic variational theory
      and time-independent non-Hermitian scattering theory. We demonstrate that only
      the eigenenergies of the resulting one-dimensional Schrodinger equation for
      different complex adiabats are required. The expression is applied to calculate
      the Penning ionization rate coefficients of an excited metastable helium atom
      with molecular hydrogen in an energy range spanning from hundreds of kelvins down
      to the millikelvin regime. Except for trivial quantities like the masses of the
      nuclei and the bond length of the diatomic molecule participating in the
      collision, one needs as input data only the complex potential energy surface
      (CPES). In calculations, we used recently obtained ab initio CPES by D.
      Bhattacharya et al. ( J. Chem. Theory Comput. 2017 , 13 , 1682 - 1690 ) without
      fitting parameters. The results show good accord with current measurements ( Nat.
      Phys. 2017 , 13 , 35 - 38 ).

PMID- 29182330
TI  - Highly Efficient Interception and Precipitation of Uranium(VI) from Aqueous
      Solution by Iron-Electrocoagulation Combined with Cooperative Chelation by
      Organic Ligands.
AB  - A new strategy combining iron-electrocoagulation and organic ligands (OGLs)
      cooperative chelation was proposed to screen and precipitate low concentrations
      (0-18.52 MUmol/L) of uranium contaminant in aqueous solution. We hypothesized
      that OGLs with amino, hydroxyl, and carboxyl groups
      hydrophobically/hydrophilically would realize precuring of uranyl ion at pH <
      3.0, and the following iron-electrocoagulation would achieve faster and more
      efficient uranium precipitation. Experimentally, the strategy demonstrated highly
      efficient uranium(VI) precipitation efficiency, especially with hydrophilic
      macromolecular OGLs. The uranium removal efficiency at optimized experimental
      condition reached 99.65%. The decrease of zeta potential and the lattice
      enwrapping between U-OGLs chelates and flocculation precursor were ascribed to
      the enhanced uranium precipitation activity. Uranium was precipitated as oxides
      of U(VI) or higher valences that were easily captured in aggregated micelles
      under low operation current potential. The actual uranium tailing wastewater was
      treated, and a satisfied uranium removal efficiency of 99.02% was discovered.
      After elution of the precipitated flocs, a concentrated uranium solution (up to
      106.52 MUmol/L) with very few other metallic impurities was obtained. Therefore,
      the proposed strategy could remove uranium and concentrate it concurrently. This
      work could provide new insights into the purification and recovery of uranium
      from aqueous solutions in a cost-effective and environmentally friendly process.

PMID- 29182331
TI  - Polyoxygenated Steroids from the Sponge Clathria gombawuiensis.
AB  - Six new polyoxygenated steroids (1-6) along with clathriol (7) were isolated from
      the Korean marine sponge Clathria gombawuiensis. Based upon the results of
      combined spectroscopic analyses, the structures of gombasterols A-F (1-6) were
      elucidated to be those of highly oxygenated steroids possessing a
      3beta,4alpha,6alpha,7beta-tetrahydroxy or equivalent (7beta-sodium O-sulfonato
      for 3) substitution pattern and a C-15 keto group as common structural motifs.
      The relative and absolute configurations of these steroids, including the rare
      14beta configuration of 1-4, were determined by a combination of NOESY, J-based
      analyses, the 2-methoxy-2-(trifluoromethyl)phenylacetic acid (MTPA) method, and X
      ray crystallographic analysis. The absolute configuration of 7 was also assigned
      by these methods. These compounds moderately enhanced 2-deoxy-2-[(7-nitro-2,1,3
      benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) uptake in differentiated 3T3-L1
      adipocytes and phosphorylation of AMP-activated protein kinase (AMPK) and acetyl
      CoA carboxylase (ACC) in differentiated mouse C2C12 skeletal myoblasts.

PMID- 29182332
TI  - Quantitative Evaluation of Serum Proteins Uncovers a Protein Signature Related to
      Maturity-Onset Diabetes of the Young (MODY).
AB  - Maturity-onset diabetes of the young (MODY) is an inherited monogenic type of
      diabetes. Genetic mutations in MODY often cause nonsynonymous changes that
      directly lead to the functional distortion of proteins and the pathological
      consequences. Herein, we proposed that the inherited mutations found in a MODY
      family could cause a disturbance of protein abundance, specifically in serum. The
      serum samples were collected from a Uyghur MODY family through three generations,
      and the serum proteins after depletion treatment were examined by quantitative
      proteomics to characterize the MODY-related serum proteins followed by
      verification using target quantification of proteomics. A total of 32 serum
      proteins were preliminarily identified as the MODY-related. Further verification
      test toward the individual samples demonstrated the 12 candidates with the
      significantly different abundance in the MODY patients. A comparison of the 12
      proteins among the sera of type 1 diabetes, type 2 diabetes, MODY, and healthy
      subjects was conducted and revealed a protein signature related with MODY
      composed of the serum proteins such as SERPINA7, APOC4, LPA, C6, and F5.

PMID- 29182333
TI  - Reply to "Comment on '308 nm Photolysis of Nitric Acid in the Gas Phase, on
      Aluminum Surfaces, and on Ice Films'".

PMID- 29182334
TI  - Correction to "Exciton Dynamics in Disordered Poly(p-phenylenevinylene). 2.
      Exciton Diffusion".

PMID- 29182335
TI  - Proteomic Landscape of Patient-Derived CD4+ T Cells in Recent-Onset Type 1
      Diabetes.
AB  - The pathophysiology underlying the autoimmune disease type 1 diabetes (T1D) is
      poorly understood. Obtaining an accurate proteomic profile of the T helper cell
      population is essential for understanding the pathogenesis of T1D. Here, we
      performed in-depth proteomic profiling of peripheral CD4+ T cells in a pediatric
      cohort to identify cellular signatures associated with the onset of T1D. Using
      only 250 000 CD4+ T cells per patient, isolated from biobanked PBMC samples, we
      identified nearly 6000 proteins using deep-proteome profiling with LC-MS/MS data
      independent acquisition. Our analysis revealed an inflammatory signature in
      patients with T1D; this signature is characterized by circulating mediators of
      neutrophils, platelets, and the complement system. This signature likely reflects
      the inflammatory extracellular milieu, which suggests that activation of the
      innate immune system plays an important role in disease onset. Our results
      emphasize the potential value of using high-resolution LC-MS/MS to investigate
      limited quantities of biobanked samples to identify disease-relevant proteomic
      patterns. Proteomic profiles of 114 individuals have been deposited in a
      comprehensive portable repository serving as a unique resource for CD4+ T cell
      expression in the context of both health and T1D disease.

PMID- 29182336
TI  - Total Synthesis of the Marine Alkaloid Discoipyrrole C via the MoOPH-Mediated
      Oxidation of a 2,3,5-Trisubstituted Pyrrole.
AB  - A total synthesis of the marine alkaloid discoipyrrole C (3) is described. In the
      pivotal step, the 2,3,5-trisubstituted pyrrole 19 was treated with MoOPH in the
      presence of MeOH, and the resulting methoxylated 1,2-dihydro-3H-pyrrol-3-one 20
      subjected to reaction with potassium carbonate in MeOH then trifluoroacetic acid
      and H2O. This gave a mixture of target 3 and its dehydration product, and the
      structure of the former compound was confirmed by single-crystal X-ray analysis.

PMID- 29182337
TI  - pH-Driven Reversible Self-Assembly of Micron-Scale DNA Scaffolds.
AB  - Inspired by cytoskeletal scaffolds that sense and respond dynamically to
      environmental changes and chemical inputs with a unique capacity for
      reconfiguration, we propose a strategy that allows the dynamic and reversible
      control of the growth and breakage of micron-scale synthetic DNA structures upon
      pH changes. We do so by rationally designing a pH-responsive system composed of
      synthetic DNA strands that act as pH sensors, regulators, and structural
      elements. Sensor strands can dynamically respond to pH changes and route
      regulatory strands to direct the self-assembly of structural elements into
      tubular structures. This example represents the first demonstration of the
      reversible assembly and disassembly of micron-scale DNA scaffolds using an
      external chemical input other than DNA. The capacity to reversibly modulate
      nanostructure size may promote the development of smart devices for catalysis or
      drug-delivery applications.

PMID- 29182338
TI  - Sucupiranins A-L, Furanocassane Diterpenoids from the Seeds of Bowdichia
      virgilioides.
AB  - Twelve new furanocassane diterpenoids, sucupiranins A-L (1-12), and three known
      compounds (13-15) were isolated from the seeds of Bowdichia virgilioides. The
      structures of the compounds were elucidated via 1H and 13C NMR analysis,
      including 2D NMR (1H-1H COSY, HSQC, HMBC, and NOESY); HRMS data; and X-ray
      crystallographic analysis. The absolute configurations were defined using their
      electronic circular dichroism (ECD) spectra by applying the exciton chirality
      method to the bis-p-bromobenzoate of compound 13. Sucupiranin J (10) inhibited
      lipopolysaccharide-induced nitric oxide production (IC50 30.6 MUM), whereas
      sucupiranins J (10), K (11), and 13 exhibited weak antimalarial activity against
      Plasmodium falciparum K1 with IC50 values of 32.2, 23.5, and 22.9 MUM and
      selectivity indices of 4.3, 1.9, and >12.0 (MRC-5/K1), respectively.

PMID- 29182339
TI  - Convergent Synthesis of Digalactosyl Diacylglycerols.
AB  - Efficient convergent chemical syntheses of digalactosyl diacylglycerols (DGDGs),
      which have both a galactose-galactose alpha(1->6)-linkage and a galactose
      glycerol beta-linkage along with a diacylglycerol containing various kinds of
      fatty acids, have been accomplished. In order to achieve a concise synthesis, we
      chose to use allylic protective groups as permanent protective groups. We have
      also achieved alpha- and beta-selective glycosylations for the respective
      linkages with high yields as the key steps.

PMID- 29182340
TI  - Metal-Free Thermal Activation of Molecular Oxygen Enabled Direct alpha-CH2
      Oxygenation of Free Amines.
AB  - Direct oxidation of alpha-CH2 group of free amines is hard to achieve due to the
      higher reactivity of amine moiety. Therefore, oxidation of amines involves the
      use of sophisticated metallic reagents/catalyst in the presence or absence of
      hazardous oxidants under sensitive reaction conditions. A novel method for direct
      C-H oxygenation of aliphatic amines through a metal-free activation of molecular
      oxygen has been developed. Both activated and unactivated free amines were
      oxygenated efficiently to provide a wide variety of amides (primary, secondary)
      and lactams under operationally simple conditions without the aid of metallic
      reagents and toxic oxidants. The method has been applied to the synthesis of
      highly functionalized amide-containing medicinal drugs, such as O-Me-alibendol
      and -buclosamide.

PMID- 29182341
TI  - Ruthenium-Catalyzed meta-Carboxylation.
AB  - The meta-carboxylation of arenes containing pyridine and other azine-directing
      groups is reported. Using carbon tetrabromide as the C1 source, ruthenium(III)
      trichloride catalysis enables functionalization of the arene meta-C-H position,
      affording carboxy methyl ester products after in situ reaction with methanol.

PMID- 29182342
TI  - Controllable Switching Filaments Prepared via Tunable and Well-Defined Single
      Truncated Conical Nanopore Structures for Fast and Scalable SiOx Memory.
AB  - The controllability of switching conductive filaments is one of the central
      issues in the development of reliable metal-oxide resistive memory because the
      random dynamic nature and formation of the filaments pose an obstacle to
      desirable switching performance. Here, we introduce a simple and novel approach
      to control and form a single silicon nanocrystal (Si-NC) filament for use in SiOx
      memory devices. The filament is formed with a confined vertical nanoscale gap by
      using a well-defined single vertical truncated conical nanopore (StcNP)
      structure. The physical dimensions of the Si-NC filaments such as number, size,
      and length, which have a significant influence on the switching properties, can
      be simply engineered by the breakdown of an Au wire through different StcNP
      structures. In particular, we demonstrate that the designed SiOx memory junction
      with a StcNP of pore depth of ~75 nm and a bottom diameter of ~10 nm exhibited a
      switching speed of up to 6 ns for both set and reset process, significantly
      faster than reported SiOx memory devices. The device also exhibited a high ON-OFF
      ratio, multistate storage ability, acceptable endurance, and retention stability.
      The influence of the physical dimensions of the StcNP on the switching features
      is discussed based on the simulated temperature profiles of the Au wire and the
      nanogap size generated inside the StcNP structure during electromigration.

PMID- 29182343
TI  - Quantitative Evidence for Lanthanide-Oxygen Orbital Mixing in CeO2, PrO2, and
      TbO2.
AB  - Understanding the nature of covalent (band-like) vs ionic (atomic-like) electrons
      in metal oxides continues to be at the forefront of research in the physical
      sciences. In particular, the development of a coherent and quantitative model of
      bonding and electronic structure for the lanthanide dioxides, LnO2 (Ln = Ce, Pr,
      and Tb), has remained a considerable challenge for both experiment and theory.
      Herein, relative changes in mixing between the O 2p orbitals and the Ln 4f and 5d
      orbitals in LnO2 are evaluated quantitatively using O K-edge X-ray absorption
      spectroscopy (XAS) obtained with a scanning transmission X-ray microscope and
      density functional theory (DFT) calculations. For each LnO2, the results reveal
      significant amounts of Ln 5d and O 2p mixing in the orbitals of t2g (sigma
      bonding) and eg (pi-bonding) symmetry. The remarkable agreement between
      experiment and theory also shows that significant mixing with the O 2p orbitals
      occurs in a band derived from the 4f orbitals of a2u symmetry (sigma-bonding) for
      each compound. However, a large increase in orbital mixing is observed for PrO2
      that is ascribed to a unique interaction derived from the 4f orbitals of t1u
      symmetry (sigma- and pi-bonding). O K-edge XAS and DFT results are compared with
      complementary L3-edge and M5,4-edge XAS measurements and configuration
      interaction calculations, which shows that each spectroscopic approach provides
      evidence for ground state O 2p and Ln 4f orbital mixing despite inducing very
      different core-hole potentials in the final state.

PMID- 29182344
TI  - Light Emission from Gold Nanoparticles under Ultrafast Near-Infrared Excitation:
      Thermal Radiation, Inelastic Light Scattering, or Multiphoton Luminescence?
AB  - Gold nanoparticles emit broad-band upconverted luminescence upon irradiation with
      pulsed infrared laser radiation. Although the phenomenon is widely observed,
      considerable disagreement still exists concerning the underlying physics, most
      notably over the applicability of concepts such as multiphoton absorption,
      inelastic scattering, and interband vs intraband electronic transitions. Here, we
      study single particles and small clusters of particles by employing a spectrally
      resolved power-law analysis of the irradiation-dependent emission as a sensitive
      probe of these physical models. Two regimes of emission are identified. At low
      irradiance levels of kW/cm2, the emission follows a well-defined integer-exponent
      power law suggestive of a multiphoton process. However, at higher irradiance
      levels of several kW/cm2, the nonlinearity exponent itself depends on the photon
      energy detected, a tell-tale signature of a radiating heated electron gas. We
      show that in this regime, the experiments are incompatible with both interband
      transitions and inelastic light scattering as the cause of the luminescence,
      whereas they are compatible with the notion of luminescence linked to intraband
      transitions.

PMID- 29182345
TI  - Formation of Micrometer Scale Metal Structures on Glass by Selective Electroless
      Plating on Photopatterned Titanium and Copper Containing Films.
AB  - A procedure for formation of catalytic SiO2 substrate adhesive layer patterns and
      selective electrochemical metal deposition on the catalyst images was
      investigated. A photoreactive solution containing a diazonaphthoquinone sulfonate
      ester and Ti and Cu complexes was developed to deposit Cu catalyst-TiO2 adhesive
      layer latent images on glass. Sub-micrometer/micrometer scale positive tone
      photoactive TiCu complex film patterns were formed using a conventional
      photolithography technique. The Cu ions in 40-50 nm thick Ti and Cu oxide layers
      formed by pyrolysis of the TiCu complex films were reduced, residual Cu displaced
      with Pd then the porous Ti oxide structure filled and plated with Cu by selective
      electroless then electrolytic plating. Annealing the Cu plating filled TiO2
      layers on glass resulted in formation of a smooth Ti3+/Cu1+ oxide interface that
      enabled formation of 20 MUm thick Cu deposits on glass substrate with up to 1
      kN/m adhesion strength. The adhesion strength was attributed to chemical bonding
      of Ti3+ and Cu1+ oxides to the glass and Ti4+ oxide to the Cu plating that was
      formed upon annealing the Cu filled TiO2 interlayer. Furthermore, a dip coating
      procedure was adapted that allowed copper film deposition on the entire surface
      of a 300 MUm thick glass substrate with 50 MUm in diameter holes enabling
      formation of electrically conductive through glass substrate interconnects.

PMID- 29182346
TI  - Phosphine-Catalyzed Asymmetric Synthesis of alpha-Quaternary Amine via Umpolung
      gamma-Addition of Ketimines to Allenoates.
AB  - A first phosphine-catalyzed enantioselective umpolung gamma-addition of ketimines
      to allenoates has been developed that provides efficient access to optically
      active gamma,delta-unsaturated alpha-amino esters and delta-amino esters with a
      chiral tertiary stereocenter under mild conditions. The salient features of this
      reaction include general substrate scope, mild conditions, good yields, high
      enantioselectivity, ease of scale-up to gram scale, and further transformations.

PMID- 29182347
TI  - Efficient and Adaptive Methods for Computing Accurate Potential Surfaces for
      Quantum Nuclear Effects: Applications to Hydrogen-Transfer Reactions.
AB  - We present two sampling measures to gauge critical regions of potential energy
      surfaces. These sampling measures employ (a) the instantaneous quantum wavepacket
      density, an approximation to the (b) potential surface, its (c) gradients, and
      (d) a Shannon information theory based expression that estimates the local
      entropy associated with the quantum wavepacket. These four criteria together
      enable a directed sampling of potential surfaces that appears to correctly
      describe the local oscillation frequencies, or the local Nyquist frequency, of a
      potential surface. The sampling functions are then utilized to derive a
      tessellation scheme that discretizes the multidimensional space to enable
      efficient sampling of potential surfaces. The sampled potential surface is then
      combined with four different interpolation procedures, namely, (a) local Hermite
      curve interpolation, (b) low-pass filtered Lagrange interpolation, (c) the
      monomial symmetrization approximation (MSA) developed by Bowman and co-workers,
      and (d) a modified Shepard algorithm. The sampling procedure and the fitting
      schemes are used to compute (a) potential surfaces in highly anharmonic hydrogen
      bonded systems and (b) study hydrogen-transfer reactions in biogenic volatile
      organic compounds (isoprene) where the transferring hydrogen atom is found to
      demonstrate critical quantum nuclear effects. In the case of isoprene, the
      algorithm discussed here is used to derive multidimensional potential surfaces
      along a hydrogen-transfer reaction path to gauge the effect of quantum-nuclear
      degrees of freedom on the hydrogen-transfer process. Based on the decreased
      computational effort, facilitated by the optimal sampling of the potential
      surfaces through the use of sampling functions discussed here, and the accuracy
      of the associated potential surfaces, we believe the method will find great
      utility in the study of quantum nuclear dynamics problems, of which application
      to hydrogen-transfer reactions and hydrogen-bonded systems is demonstrated here.

PMID- 29182348
TI  - Solvation of the Guanidinium Ion in Pure Aqueous Environments: A Theoretical
      Study from an "Ab Initio"-Based Polarizable Force Field.
AB  - We report simulation results regarding the hydration process of the guanidinium
      cation in water droplets and in bulk liquid water, at a low concentration of 0.03
      M, performed using a polarizable approach to model both water/water and ion/water
      interactions. In line with earlier theoretical studies, our simulations show a
      preferential orientation of guanidinium at water-vacuum interfaces, i.e., a
      parallel orientation of the guanidinium plane to the aqueous surface. In an
      apparent contradiction with earlier simulation studies, we show also that
      guanidinium has a stronger propensity for the cores of aqueous systems than the
      ammonium cation. However, our bulk simulation conditions correspond to weaker
      cation concentrations than in earlier studies, by 2 orders of magnitude, and that
      the same simulations performed using a standard nonpolarizable force field leads
      to the same conclusion. From droplet data, we extrapolate the guanidinium single
      hydration enthalpy value to be -82.9 +/- 2.2 kcal mol-1. That is about half as
      large as the sole experimental estimate reported to date, about -144 kcal mol-1.
      Our result yields a guanidinium absolute bulk hydration free energy at ambiant
      conditions to be -78.4 +/- 2.6 kcal mol-1, a value smaller by 3 kcal mol-1
      compared to ammonium. The relatively large magnitude of our guanidinium hydration
      free energy estimate suggests the Gdm+ protein denaturing properties to result
      from a competition between the cation hydration effects and the cation/protein
      interactions, a competition that can be modulated by weak differences in the
      protein or in the cation chemical environment.

PMID- 29182349
TI  - Cephanolides A-J, Cephalotane-Type Diterpenoids from Cephalotaxus sinensis.
AB  - Ten new cephalotane-type diterpenoids, cephanolides A-J (1-10), and two known
      analogues were isolated and characterized from Cephalotaxus sinensis. Compounds 1
      3 represent the first examples of A-ring-contracted cephalotane-type
      dinorditerpenoids, and compound 4 is an A-ring-contracted norditerpenoid. The
      biosynthetic pathways for compounds 1-4 are postulated with the coexisting
      cephalotane-type troponoids as the precursors. Compounds 11 and 12 showed
      significant cytotoxicities against a panel of tumor cell lines (A549, KB, HL-60,
      and HT-29) with IC50 values ranging from 0.464 to 6.093 MUM.

PMID- 29182350
TI  - Using the 4 Pillars to increase vaccination among high-risk adults: who benefits?
AB  - OBJECTIVES: To compare changes in vaccination rates (pneumococcal polysaccharide
      vaccine [PPSV]; tetanus, diphtheria, and pertussis [Tdap] vaccine; and influenza
      vaccine) among high-risk adults following an intervention (June 1, 2013, to
      January 31, 2015) that used the 4 Pillars Practice Transformation Program (4
      Pillars Program). STUDY DESIGN: Post hoc analysis of data from a randomized
      controlled cluster trial. METHODS: Eighteen primary care practices received staff
      education, guidance for using the 4 Pillars Program, and support for a practice
      immunization champion. Paired t tests were used to compare vaccination rates
      separately for those with diabetes, chronic lung or chronic heart disease, or
      other high-risk conditions. Student's t tests were used to compare vaccination
      rates across high-risk conditions. Generalized estimating equation modeling was
      used to determine the likelihood of vaccination. RESULTS: Based on International
      Classification of Diseases, Ninth Revision, Clinical Modification codes, 4737
      patients aged 18 to 64 years were identified as having diabetes (n = 1999),
      chronic heart disease (n = 658), chronic lung disease (n = 1682), or another high
      risk condition (n = 764). PPSV uptake increased by 12.2 percentage points (PP),
      Tdap vaccination increased by 11.4 PP, and influenza vaccination increased by 4.8
      PP. In regression analyses, patients with diabetes (odds ratio [OR], 2.2; 95% CI,
      1.80-2.73), chronic lung disease (OR, 1.50; 95% CI, 1.21-1.87), or chronic heart
      disease (OR, 1.32; 95% CI, 1.02-1.71) were more likely to receive PPSV than those
      without the respective high-risk condition. Those with diabetes (OR, 1.14; 95%
      CI, 1.01-1.28) or chronic lung disease (OR, 1.14; 95% CI, 1.01-1.30) were more
      likely to receive an influenza vaccine than those without the respective
      condition. The likelihood of Tdap vaccination was not significantly associated
      with any of the chronic conditions tested. CONCLUSIONS: An intervention including
      the 4 Pillars Program was associated with significant increases in vaccination of
      high-risk adults. However, the overall uptake of recommended vaccines for those
      with high-risk conditions remained below national goals.

PMID- 29182351
TI  - The influence of provider characteristics and market forces on response to
      financial incentives.
AB  - OBJECTIVES: Alternative payment models, such as accountable care organizations,
      use financial incentives as levers for change to facilitate the transition from
      volume to value. However, implementation raises concerns about adverse changes in
      market competition and the resultant physician response. We sought to identify
      physician characteristics and market-level factors associated with variation in
      response to financial incentives for cancer care that may ultimately be leveraged
      in risk-shared payment models. STUDY DESIGN: Retrospective cohort study of
      physicians providing minimally invasive bladder cancer procedures to fee-for
      service Medicare beneficiaries. METHODS: We examined the relationship of between
      group differences in market-level factors (competition [Herfindahl-Hirschman
      Index (HHI)] and provider density) and physician-level factors (use of unique
      billing codes, number of billing codes per patient, and competing financial
      interest) to responsiveness to financial incentives. RESULTS: Incentive
      responsive providers had increased odds (odds ratio [OR], 1.19; 95% CI, 1.04
      1.35) of practicing in markets with the highest quartile of provider density but
      not HHI (OR, 0.96; 95% CI, 0.87-1.05). Incentive-responsive providers were more
      likely to bill in the highest quartile for unique codes (OR, 1.49; 95% CI, 1.32
      1.69) and codes per patient (OR, 1.18; 95% CI, 1.11-1.25) and less likely to have
      a competing financial interest (OR, 0.76; 95% CI, 0.72-0.81). CONCLUSIONS:
      Responsiveness to financial incentives in cancer care is associated with high
      market provider density, profit-maximizing billing behavior, and lack of
      competing financial ownership interests. Identifying physicians and markets
      responsive to financial incentives may ultimately promote the successful
      implementation of alternative payment models in cancer care.

PMID- 29182352
TI  - Patients' perspectives of care management: a qualitative study.
AB  - OBJECTIVES: Risk-stratified care management is a cornerstone of patient-centered
      medical home models, but studies on patients' perspectives of care management are
      scarce. We explored patients' experiences with care management, what they found
      useful, and what needs improvement. STUDY DESIGN: Semi-structured qualitative
      telephone interviews. METHODS: We interviewed 43 high-risk patients or their
      caregivers who were receiving care management from 11 practices in CMS'
      Comprehensive Primary Care initiative, provided by nurse care managers (9
      practices) or the physician (2 [solo] practices). RESULTS: Patients' perceptions
      of care management were mixed. Patients who had regular contact with, and a
      desire to work with, their care manager valued the care management services
      provided. These patients valued care managers who listened to them and explained
      their conditions and options in lay terms, helped them navigate the healthcare
      system and community resources, and followed up after hospitalizations. However,
      one-fifth of the patients in practices that used nurse care managers could not
      identify their care manager although we: 1) sampled patients who had recent
      contact with their care manager and 2) defined the care manager's roles and
      provided examples of typical care management activities. Patients' interactions
      with care managers from health plans and hospitals contributed to confusion.
      CONCLUSIONS: Practices can improve patient buy-in for care management through in
      person introductions to care managers by their physicians, offering care
      management to patients who need and are interested in it, broader agreement about
      terminology and the role of care managers and care plans, and better coordination
      with care management from insurers and hospitals.

PMID- 29182353
TI  - Impact of health reform on young adult prescription medication utilization.
AB  - OBJECTIVES: To assess the impact of the Affordable Care Act dependent coverage
      provision on outpatient prescription expenditures among young adults and to
      characterize medication types that are prescribed for young adults. STUDY DESIGN:
      Quasi-experimental. METHODS: Using data from the Medical Expenditure Panel Survey
      from 2007 to 2009 and 2011 to 2013, difference-in-differences (DID) analyses
      estimated the provision's impact among young adults aged 19 to 25 years versus
      those aged 26 to 34 years. Five outcomes related to prescription medication
      access and utilization were evaluated, including whether young adults were unable
      to get necessary medications in the past year due to cost and whether there were
      changes in total, out-of-pocket (OOP), and private expenditures and the share of
      total expenditures paid OOP. DID analyses were also carried out for medication
      expenditures by class. RESULTS: There were a total of 19,165 young adults aged 19
      to 25 years and 23,892 aged 26 to 34 years. After adjusting for demographic and
      socioeconomic factors, provision implementation (DID coefficient P <=.05) was
      associated with an increase in total expenditures (by 3.8 percentage points),
      including those paid by private insurance (7.6 percentage points), and decreases
      in OOP expenditures and the share of total expenditures paid OOP (4.4 and 1.2
      percentage points, respectively). Commonly used medications were anti-infectives,
      central nervous system agents, and hormones. Expenditures significantly increased
      for anti-infectives and decreased for hormones and psychotherapeutics.
      CONCLUSIONS: The dependent coverage provision was associated with an increase in
      prescription medication expenditures, especially for anti-infectives, among young
      adults. The amount of expenditures paid by private insurers increased, whereas
      they decreased for OOP spending.

PMID- 29182354
TI  - Reframing the unaffordability debate: patient responsibility for physician care.
AB  - OBJECTIVES: Public discussion suggests that rising out-of-pocket costs have
      dramatically reduced the value of insurance and led to patients doing without
      needed care. Our aim was to ascertain trends in patient responsibility for cost
      sharing. STUDY DESIGN: We used data from an organization that serves over 78,000
      healthcare providers and has access to visit-level data, including the amounts
      paid by patients. These practices are broadly representative of physicians and
      patients nationally. METHODS: We analyzed trends in patient obligations among a
      cohort of about 21,000 providers in 1078 practices who had used athenahealth
      software since 2011, including primary care physicians, obstetricians and
      gynecologists, surgeons, and some other specialists. Our analysis focused on what
      commercially insured patients pay out of pocket when seeking ambulatory care.
      RESULTS: The average patient obligation for approximately 2.5 million primary
      care visits each year rose from $23.52 per visit in 2011 to $26.40 per visit in
      2015, for an overall increase of $2.88, or about 3% annually. This rate of
      increase is moderate and below growth in overall healthcare spending during the
      same time period. CONCLUSIONS: Average increases in patient obligations for
      outpatient visits in recent years have been fairly moderate, and multiple sources
      of survey data suggest that consumers' concerns about overall affordability are
      decreasing. The high cost of healthcare continues to pose challenges, both at the
      individual level and for society as a whole. Nevertheless, it is important that
      potential strategies to improve affordability are informed by trends in patient
      obligations.

PMID- 29182355
TI  - Electronic reminder's role in promoting human papillomavirus vaccine use.
AB  - OBJECTIVES: To study the association of using an electronic health record (EHR)'s
      clinical reminder functionality with increased human papillomavirus (HPV) vaccine
      administration among US office-based physicians. STUDY DESIGN: National
      Ambulatory Medical Care Survey data from 2007-2012 were pooled together to
      determine if EHR systems that employ clinical reminders are associated with
      increased immunization rates in different populations. METHODS: The
      administration of HPV vaccine served as the dependent variable, with the EHR
      reminder being the primary independent variable of interest. Logit regression was
      used to assess the relationship between using EHR reminders and HPV vaccine
      administration. RESULTS: Analyses indicated that compared with physicians without
      clinical reminder functions, physicians with clinical reminder functions were
      more likely to order HPV vaccines. Clinical reminder functions were particularly
      effective at increasing HPV vaccine use among adolescent males. CONCLUSIONS:
      Overall, physicians who report using clinical reminders were more likely to order
      HPV immunizations. However, the association of clinical reminders with HPV
      immunizations was not significant in the younger adolescent subpopulation.
      Further, given that HPV incidence decreases significantly even with small gains
      in vaccination rates, the increase in HPV immunizations found in the male
      population aged 11 to 21 years is promising. Therefore, targeting males to
      receive HPV vaccination immunizations through clinical reminders provides a
      positively disproportionate return on vaccination rates and disease burden.

PMID- 29182356
TI  - Improving antibiotic stewardship: a stepped-wedge cluster randomized trial.
AB  - OBJECTIVES: Antibiotic stewardship is key to optimizing patient outcomes and
      affordable care. The study objective was to examine the effect of provider
      education and clinical decision support (CDS) on antibiotic prescribing for acute
      sinusitis among providers of varying experience. STUDY DESIGN: A stepped-wedge
      cluster randomized intervention to evaluate antibiotic use for acute sinusitis
      encounters at 126 Kaiser Permanente Southern California clinics between September
      2014 and April 2015. METHODS: The primary outcome was receipt of an antibiotic
      prescription. Multivariate analysis adjusted for patient, provider, and medical
      center characteristics. Secondary analyses described sinusitis and other common
      upper respiratory infection (URI) diagnoses and antibiotic use during the study
      period compared with prior years. Chart review of a random sample reported the
      proportion of encounters receiving guideline-concordant antibiotics. RESULTS:
      Analysis of 21,949 encounters (10,491 pre- and 11,458 post intervention) showed
      CDS reduced the use of antibiotics (adjusted odds ratio [AOR], 0.78; 95% CI, 0.71
      0.87), although the pre-post absolute difference was small (85.9% vs 83.9%,
      respectively). Education had a large initial effect (AOR, 0.51; 95% CI, 0.46
      0.57), which did not persist. Increasing years of provider experience raised the
      rates of antibiotic prescribing, but did not have a significant interaction with
      CDS (P = .19). The effect of CDS varied by medical center (P <.001). In addition,
      sinusitis diagnoses decreased post intervention, with no overall increase in
      antibiotic prescribing for URI diagnoses. Lastly, guideline-concordant antibiotic
      use increased by 14%. CONCLUSIONS: Provider education and CDS improved antibiotic
      stewardship and changed diagnosis patterns. The benefits of education were brief,
      and CDS effectiveness varied by medical center.

PMID- 29182357
TI  - Changes in cardiovascular care provision after the Affordable Care Act.
AB  - OBJECTIVES: Physicians are gatekeepers to preventive care recommended by the US
      Preventive Services Task Force (USPSTF). We aimed to determine whether the
      Affordable Care Act (ACA) was associated with changes in physicians' provision of
      preventive cardiovascular services, focusing primarily on patients with employer
      sponsored health plans. STUDY DESIGN: Quasi-experimental, difference-in
      differences (DID) approach. METHODS: We analyzed National Ambulatory Medical Care
      Survey and National Hospital Ambulatory Medical Care Survey data from 2006 to
      2013. Using a quasi-experimental DID approach with multivariate logistic models,
      we compared trends in preventive cardiovascular services delivered during
      physician visits among target and control populations prior to the ACA's
      provisions. RESULTS: The ACA was associated with an increase in use of diabetes
      screening (3.9% in 2006-2010 [third quarter] to 7.6% in 2010 [fourth quarter]
      2013; DID, +3.5 per 100 visits; 95% CI, 1.1-5.9), tobacco use screening in adults
      (64.4% in 2006-2010 to 74.5% in 2010-2013; DID, +11.6 per 100 visits; 95% CI, 4.8
      18.3), aspirin therapy in men (11.1% in 2006-2010 to 13.5% in 2010-2013; DID,
      +2.9 per 100 visits; 95% CI, 1.1-4.6), and hypertension screening (73.2% in 2006
      2010 to 76.4% in 2010-2013; DID, +9.9 per 100 visits; 95% CI, 2.8-16.9).
      CONCLUSIONS: Provision of cardiovascular preventive care increased for some
      USPSTF-recommended services following enactment of the ACA, with evidence of a
      sex disparity in aspirin use. Other complementary policy approaches may further
      enhance uptake of evidence-based clinical preventive services.

PMID- 29182358
TI  - Diabetes care improvement in pharmacist- versus nurse-supported patient-centered
      medical homes.
AB  - OBJECTIVES: In 2009 and 2010, 17 primary care sites within 1 healthcare system
      became patient-centered medical homes (PCMHs), but the sites trained different
      personnel (pharmacists vs nurses) to improve diabetes care using self-management
      support (SMS). We report the challenges and successes of our efforts to: 1)
      assemble a new multipayer (Medicare, Medicaid, commercial) claims dataset linked
      to a clinical registry and 2) use the new dataset to perform comparative
      effectiveness research on implementation of the 2 SMS models. STUDY DESIGN:
      Longitudinal cohort study. METHODS: We lost permission to use private-payer data.
      Therefore, we used claims from Medicare fee-for-service and Medicare/Medicaid
      dual-eligible patients merged with chronic disease registry data. We studied 2008
      to 2010, which included 1 year pre- and 1 year post the 2009 implementation time
      period. Outcomes were outpatient and emergency department visits,
      hospitalizations, care process (use of statin), and 3 intermediate outcomes
      (glycemic control, blood pressure [BP], and low-density lipoprotein cholesterol
      [LDL-C]). RESULTS: In our sample of 2826 patients, quality of care improved and
      utilization decreased over the 2.5 years. Both approaches improved lipid control
      (LDL-C decreased by an average of 4 mg/dL for pharmacy-SMS and 5.6 mg/dL for
      nurse-SMS) and diastolic BP (-1.5 mm Hg for pharmacy-SMS and -1.3 mm Hg for nurse
      SMS), whereas only the pharmacy-led approach decreased primary care visits (by
      0.8 visits). The groups differed slightly on 2 measures (glycated hemoglobin,
      systolic BP) with respect to the trajectory of improvement over time, but
      performance was similar by 2.5 years. CONCLUSIONS: Diabetes care improved during
      PCMH implementation systemwide, supporting both nurse-led and pharmacist-led SMS
      models.

PMID- 29182360
TI  - Relationship between smell identification testing and the neuropsychological
      assessment of dementia in community-dwelling adults.
AB  - The objective of this research was to investigate the relationship of the
      University of Pennsylvania Smell Identification Test (UPSIT) with
      neuropsychological tests and identify the utility of the UPSIT in detecting
      cognitive impairment. This research was an archival study of neuropsychological
      test results obtained from 70 clients (30 male/40 female) of a community-based
      memory clinic. The sample had an average age of 69.7 (SD = 9.7) and education of
      14.6 (SD = 2.8) years. Hypotheses were tested using correlations, receiver
      operating characteristic (ROC) curves, and logistic regression. The UPSIT showed
      significant, weak to moderate correlations with neuropsychological tests. The
      UPSIT raw score correlated significantly with all but one cognitive ability
      domain. The UPSIT T-score was significantly correlated with all cognitive
      domains. Obtained areas under the ROC curve (AUC) for the UPSIT ranged from .60
      to .87. The AUCs of the UPSIT did not differ significantly from verbal semantic
      fluency tests, but the Repeatable Battery for the Assessment of
      Neuropsychological Status Total Scale and Delayed Memory index tended to produce
      larger AUCs than the UPSIT. Results from step-wise logistic regressions suggest
      that the UPSIT raw score provides unique information beyond its relationship to
      age. Olfaction relates broadly to cognitive ability and may be sensitive to early
      symptoms of cognitive decline. Further research is needed to explore the
      relationships between smell identification tests and neuropsychological
      assessment.

PMID- 29182359
TI  - Validation of a claims-based algorithm to characterize episodes of care.
AB  - OBJECTIVES: Although hospitals face increasing pressure from payers to improve
      the efficiency of healthcare delivery beyond the index hospitalization, they
      often lack information on postdischarge events. The Michigan Value Collaborative
      (MVC) developed a claims-based algorithm to provide hospitals with data on events
      that occur to patients beyond the hospitalization. Herein, we discuss the
      validation of MVC's claims-based algorithm. STUDY DESIGN: Retrospective analysis
      of a claims-based algorithm's ability to identify specific medical events, such
      as index hospitalizations, 30-day readmissions, emergency department visits,
      skilled nursing facility admissions, home health visits, and rehabilitation
      services. The claims-based events were validated using a primary review at 63
      hospitals. METHODS: We selected 1830 Blue Cross Blue Shield of Michigan episodes
      from MVC data and asked 63 Michigan hospitals to query their medical records for
      the presence or absence of specific events. We then calculated agreement
      statistics and improved our algorithm using feedback from hospitals. RESULTS: All
      63 hospitals participated in the validation process and successfully identified
      99% of episodes in their medical records. The initial agreement between our
      algorithm and medical records was moderate for 4 postdischarge events (kappa
      ranging from 0.62-0.78) and poor for rehabilitation services (0.16). Much of the
      disagreements occurred because hospitals could not identify postdischarge events
      occurring outside of their hospital systems. Other disagreements occurred because
      of hospital coding practices. Through this analysis, the claims-based algorithm
      was improved to better reflect real-world coding practice. CONCLUSIONS: Our
      findings suggest that the MVC claims-based algorithm identifies and classifies
      claims with high fidelity and outperforms medical records in the identification
      of postdischarge events. These findings provide important insight to policy
      makers, payers, and hospital administrators about the value of claims-based data
      for the implementation of episode-based programs.

PMID- 29182362
TI  - Growth, nisA Gene Expression, and In Situ Activity of Novel Lactococcus lactis
      subsp. cremoris Costarter Culture in Commercial Hard Cheese Production.
AB  - This study evaluated in situ expression of the nisA gene by an indigenous, nisin
      A-producing (NisA+) Lactococcus lactis subsp. cremoris raw milk genotype,
      represented by strain M78, in traditional Greek Graviera cheeses under real
      factory-scale manufacturing and ripening conditions. Cheeses were produced with
      added a mixed thermophilic and mesophilic commercial starter culture (CSC) or
      with the CSC plus strain M78 (CSC+M78). Cheeses were sampled after curd cooking
      (day 0), fermentation of the unsalted molds for 24 h (day 1), brining (day 7),
      and ripening of the brined molds (14 to 15 kg each) for 30 days in a fully
      controlled industrial room (16.5 degrees C; 91% relative humidity; day 37). Total
      RNA was directly extracted from the cheese samples, and the expression of nisA
      gene was evaluated by real-time reverse transcription PCR (qRT-PCR). Agar overlay
      and well diffusion bioassays were correspondingly used for in situ detection of
      the M78 NisA+ colonies in the cheese agar plates and antilisterial activity in
      whole-cheese slurry samples, respectively. Agar overlay assays showed good growth
      (>8 log CFU/g of cheese) of the NisA+ strain M78 in coculture with the CSC and
      vice versa. The nisA expression was detected in CSC+M78 cheese samples only, with
      its expression levels being the highest (16-fold increase compared with those of
      the control gene) on day 1, followed by significant reduction on day 7 and almost
      negligible expression on day 37. Based on the results, certain intrinsic and
      mainly implicit hurdle factors appeared to reduce growth prevalence rates and
      decrease nisA gene expression, as well as the nisin A-mediated antilisterial
      activities of the NisA+ strain M78 postfermentation. To our knowledge, this is
      the first report on quantitative expression of the nisA gene in a Greek cooked
      hard cheese during commercial manufacturing and ripening conditions by using a
      novel, rarely isolated, indigenous NisA+ L. lactis subsp. cremoris genotype as
      costarter culture.

PMID- 29182361
TI  - Ado-trastuzumab emtansine (T-DM1) in HER2+ advanced breast cancer patients: does
      pretreatment with pertuzumab matter?
AB  - AIM: We evaluated the outcomes of patients treated with ado-trastuzumab
      emantasine (T-DM1) after first-line pertuzumab/trastuzumab, compared with those
      receiving a trastuzumab-only-based regimen. PATIENTS & METHODS: Patients who
      received second-line T-DM1 after pertuzumab/trastuzumab (n = 34) were compared
      with those who received only trastuzumab (n = 73). RESULTS: Overall response rate
      was 33.3% in patients with prior pertuzumab and 57.1% in the remaining subjects.
      Disease control rate was 47 and 43%, respectively, and the clinical benefit rate
      was 43.3 and 71.1%, respectively. Median progression-free survival was 5.0 and
      11.0 months, respectively (hazard ratio: 2.02; 95% CI: 1.14-3.58; p = 0.01).
      CONCLUSION: Patients treated with T-DM1 who previously received pertuzumab
      present poorer clinical outcomes compared with those receiving a trastuzumab-only
      based regimen in the first-line setting.

PMID- 29182363
TI  - Interdisciplinarity and Adapted Physical Activity.
AB  - The purpose of the paper was to draw lessons for the field of adapted physical
      activity from the interrelated literatures on interdisciplinarity, creativity,
      and team research. In each of these literatures, strategies have been identified
      that have been found to be useful by previous researchers. Lack of familiarity
      with these strategies can result in unsuccessful research projects or in the
      devotion of scarce resources to the reinvention of such strategies. The first
      section in the paper in particular addresses questions that arose at the 2016
      North American Federation of Adapted Physical Activity symposium in Edmonton,
      Alberta.

PMID- 29182364
TI  - How Journalists Characterize Health Inequalities and Redefine Solutions for
      Native American Audiences.
AB  - Many Native American communities experience severe health inequalities, including
      shorter average lifespan and higher rates of chronic illnesses. Journalism that
      serves Native Americans is a promising channel for heath communication, but only
      if scholars first understand the particular cultural contexts of indigenous
      communities. This research contributes to that goal by investigating how
      journalists serving Native American communities characterize health and the
      issues they identify with covering determinants of health. In in-depth interviews
      (N = 24), journalists contrasted how they cover health issues as embedded in
      cultural context with shallow, more negative coverage by non-Native media
      organizations. Interviews also revealed a tension between "medical" and
      "cultural" models of health, contributing to the oversaturation of certain
      issues, like diabetes, while other health topics are underrepresented. The
      journalists also expressed how social determinants and histories of oppression
      shape health inequalities, illuminating the roles of historical trauma and the
      destruction of indigenous health beliefs and behaviors. Failure to recognize
      these issues could stymie efforts to communicate about health issues facing
      Native American audiences.

PMID- 29182365
TI  - Career Development and Learning Pathways of Paralympic Coaches With a Disability.
AB  - The purpose of this study was to gain an understanding of the career development
      and learning pathways of Paralympic head coaches who previously competed as
      Paralympic athletes. Each coach participated in a semistructured interview. A
      thematic analysis of the data revealed three higher order themes, which were
      called becoming a coach, learning to coach, and lifelong learning and teaching.
      Across these themes, participants discussed interactions with other coaches and
      athletes with a disability, learning from mentors and coaching clinics, as well
      as limited formal educational opportunities they experienced transitioning from
      athlete to head coach. The findings revealed that they acquired most of their
      knowledge from a combination of knowledge gained as athletes and informal
      sources, including trial and error. They also stressed the need for enhanced
      recruiting of parasport coaches and parasport coach education opportunities that
      would enhance programs for athletes with physical disabilities, from grassroots
      to Paralympic levels.

PMID- 29182367
TI  - Associations between Poor Sleep Quality, Obesity, and the Anthropometric
      Measurements of Women in Turkey.
AB  - Recent studies have shown that poor sleep quality is significantly associated
      with obesity. The aim of this study is to examine the association of sleep
      quality with obesity and specific anthropometric measurements. A total of 105
      women aged 20-55 years with no chronic diseases participated in this study. They
      filled out the Pittsburgh Sleep Quality Index (PSQI), their anthropometric
      measurements were taken, and their dietary data were collected with a food
      frequency questionnaire (FFQ). There was no significant relationship between
      sleep quality and BMI, waist circumference, triceps skinfold thicknesses, body
      fat ratio (%), and body fat mass (p > .05), but high bread consumption was
      significantly associated with poor sleep quality (p < .05). The women with poor
      sleep quality consumed significantly more bread, but not other foods, than the
      women with good sleep quality. Sleep quality can thus be related to eating
      habits.

PMID- 29182368
TI  - Fine needle aspiration biopsy of thyroid nodule smaller than 1.0 cm: accuracy of
      TIRADS classification system in more than 1000 nodules.
AB  - OBJECTIVE: To identify whether or not the same ultrasound features can be applied
      and should be considered to support the decision as to which subcentimeter
      nodules should be biopsied with fine needle aspiration (FNAB). METHODS: Single
      institution, IRB approved, retrospective study conducted from 2008 to 2016 that
      evaluated 1094 thyroid nodules smaller than 1.0 cm that were classified according
      to TIRADS and submitted for FNAB. RESULTS: The value of FNAB of thyroid nodules
      smaller than 1.0 cm were assessed and correlated with the sonographic criteria by
      comparing the obtained results with the cytological findings in 1094 thyroid
      nodules. In the analysis considering all nodules, the proportion of malignancies
      among nodules with TIRADS 2 is 0.91% and for TIRADS 3 is 2.87%. Among those
      classified as 4A, 12.26%; with 4B classification, 34.43%; with 4C classification,
      66.6%; and among those with 5 classifications, 85.7%. CONCLUSION: In conclusion,
      the TIRADS classification system, based on the sonographic features reported
      herein, may help detect which nodules should be investigated for potential
      malignancies. Advances in knowledge: Few reports compare the efficacy of
      ultrasound-FNAB for thyroid nodules smaller than 1.0 cm in diameter. The findings
      of malignancy in this subgroup of nodules may help in the clinical follow-up of
      which patients should be submitted to an early imaging evaluation or
      intervention.

PMID- 29182369
TI  - Infertility, Adoption, and Family Formation in Indonesia.
AB  - When combined, primary and secondary infertility affects up to 21 percent of
      Indonesian couples. Based on ethnographic fieldwork with married heterosexual
      couples, I explore how intra-family adoption represents a culturally and
      religiously acceptable pathway to family formation for couples without access to
      assisted reproductive technologies. I examine how kinship is central to the
      negotiation of adoption, and to maintaining ethnic and religious continuity
      within adoptive families. I reveal how adoption can enable infertile women and
      birth mothers to achieve or escape the dominant expectations of
      heteronormativity, and discuss intra-family adoption by infertile couples in
      relation to reproductive stratification and leveling.

PMID- 29182370
TI  - Communicating Inequalities to Enhance Support for Obesity-Prevention Policies:
      The Role of Social Comparisons, Age Frames, and Emotion.
AB  - With certain populations in the United States at higher risk for obesity than
      other populations, public health advocates have attempted to draw attention to
      these inequalities to galvanize support for obesity-mitigation policies. Yet
      research comparing different messages about social inequalities indicates that
      not all social comparisons are persuasive. Drawing on Weiner's (1986) theory of
      perceived responsibility and social motivation, I experimentally tested promising
      message frames about obesity disparities. Participants (N = 653) read one of six
      messages following a 3 (social comparison frame: geographic vs. racial vs. no
      comparison) * 2 (age frame: child vs. adult) between-subjects design.
      Unexpectedly, geographic frames (rural/urban) indirectly decreased policy support
      relative to the control frame by way of increased counterarguing. Compared to
      adult frames about obesity inequalities, childhood frames evoked more sympathy
      and less internal attribution, which in turn positively predicted support for
      obesity-prevention policies. Practical and theoretical implications of these
      findings are discussed.

PMID- 29182372
TI  - Modulation of working memory load distinguishes individuals with and without
      balance impairments following mild traumatic brain injury.
AB  - OBJECTIVES: Balance and gait deficits can persist after mild traumatic brain
      injury (TBI), yet an understanding of the underlying neural mechanism remains
      limited. The purpose of this study was to investigate differences in attention
      network modulation in patients with and without balance impairments 2-8 weeks
      following mild TBI. METHODS: Using functional magnetic resonance imaging, we
      compared activity and functional connectivity of cognitive brain regions of the
      default mode, central-executive and salience networks during a 2-back working
      memory task in participants with mild TBI and balance impairments (n = 7, age 47
      +/- 15 years) or no balance impairments (n = 7, age 47 +/- 15 years). RESULTS: We
      first identified greater activation in the lateral occipital cortex in the
      balance impaired group. Second, we observed stronger connectivity of left pre
      supplementary motor cortex in the balance impaired group during the working
      memory task, which was related to decreased activation of regions within the
      salience and central executive networks and greater suppression of the default
      mode network. CONCLUSIONS: Results suggest a link between impaired balance and
      modulation of cognitive resources in patients in mTBI. Findings also highlight
      the potential importance of moving beyond traditional balance assessments towards
      an integrative assessment of cognition and balance in this population.

PMID- 29182371
TI  - Decrease in scale invariance of activity fluctuations with aging and in patients
      with suprasellar tumors.
AB  - Motor activity in healthy young humans displays intrinsic fluctuations that are
      scale-invariant over a wide range of time scales (from minutes to hours). Human
      postmortem and animal lesion studies showed that the intact function of the
      suprachiasmatic nucleus (SCN) is required to maintain such scale-invariant
      patterns. We therefore hypothesized that scale invariance is degraded in patients
      treated for suprasellar tumors that compress the SCN. To test the hypothesis, we
      investigated 68 patients with nonfunctioning pituitary macroadenoma and 22
      patients with craniopharyngioma, as well as 72 age-matched healthy controls (age
      range 21.0-70.6 years). Spontaneous wrist locomotor activity was measured for 7
      days with actigraphy, and detrended fluctuation analysis was applied to assess
      correlations over a range of time scales from minutes to 24 h. For all the
      subjects, complex scale-invariant correlations were only present for time scales
      smaller than 1.5 h, and became more random at time scales 1.5-10 h. Patients with
      suprasellar tumors showed a larger decrease in correlations at 1.5-10 h as
      compared to healthy controls. Within healthy subject, gender and age >33 year
      were associated with attenuated scale invariance. Conversely, activity patterns
      at time scales between 10 and 24 h were significantly more regular than all other
      time scales, and this was mostly associated with age. In conclusion, scale
      invariance is degraded in healthy subjects at the ages of >33 year as
      characterized by attenuation of correlations at time scales 1.5-10 h. In
      addition, scale invariance was more degraded in patients with suprasellar tumors
      as compared to healthy subjects.

PMID- 29182373
TI  - Texture analysis of 18F-FDG PET/CT for grading thymic epithelial tumours:
      usefulness of combining SUV and texture parameters.
AB  - OBJECTIVE: To retrospectively investigate the standardized uptake value (SUV)
      related and heterogeneous texture parameters individually and in combination for
      differentiating between low- and high-risk 18Fluorone-fludeoxyglucose (18F-FDG)
      avid thymic epithelial tumours (TETs) with positron emission tomography (PET)/CT.
      METHODS: SUV-related and 6 texture parameters (entropy, homogeneity,
      dissimilarity, intensity variability, size-zone variability and zone percentage)
      were compared between 11 low-risk and 23 high-risk TETs (metabolic tumour volume
      >10.0 cm3 and SUV >=2.5). Diagnostic performance was evaluated by receiver
      operating characteristic analysis. The diagnostic value of combining SUV and
      texture parameters was examined by a scoring system. RESULTS: High-risk TETs were
      significantly higher in SUVmax (p = 0.022), entropy (p = 0.038), intensity
      variability (p = 0.041) and size-zone variability (p = 0.045) than low-risk TETs.
      Diagnostic accuracies of these 4 parameters, dissimilarity and zone percentage
      which also showed significance in receiver operating characteristic analysis
      ranged between 64.7 and 73.5% without significant differences in AUC (range; 0.71
      to 0.75) (p >= 0.05 each). Each parameter was scored as 0 (negative for high
      risk) or 1 (positive for high-risk) according to each threshold criterion, then
      scores were summed [0 or 1 for low-risk TETs (median; 1); >=2 for high-risk TETs
      (median; 4)]. The sensitivity, specificity and accuracy of detecting high-risk
      TETs were 100, 81.8 and 94.1%, respectively, with an AUC of 0.99. CONCLUSION: The
      diagnostic performances of individual SUVmax and texture parameters were
      relatively low. However, combining these parameters can significantly increase
      diagnostic performance when differentiating between relatively large low- and
      high-risk 18F-FDG-avid TETs. Advances in knowledge: Combined use of SUVmax and
      texture parameters can significantly increase the diagnostic performance when
      differentiating between low- and high-risk TETs.

PMID- 29182374
TI  - Lack of association of mirSNP rs11174811 in AVPR1A gene with arterial blood
      pressure and hypertension in South Indian population.
AB  - Epigenetic regulation of arterial blood pressure mediated through mirSNPs in
      renin-angiotensin aldosterone system (RAAS) genes is a less explored hypothesis.
      Recently, the mirSNP rs11174811 in the 3'UTR of the AVPR1A gene was associated
      with higher arterial blood pressure in a large study population from the Study of
      Myocardial Infarctions Leiden (SMILE). The aim of the present study was to
      replicate the association of mirSNP rs11174811 with blood pressure outcomes and
      hypertension in a south Indian population. Four hundred and fifteen hypertensive
      cases and 416 normotensive controls were genotyped using a 5' nuclease allelic
      discrimination assay. Logistic regression was used to test the association of
      mirSNP rs11174811 with the hypertension phenotype. Censored normal regression was
      used to test the association of the polymorphism with continuous blood pressure
      outcomes such as systolic and diastolic blood pressure. The mirSNP rs11174811 did
      not show any significant association with hypertension. The adjusted odds ratio
      was 1.02, with 95% CI of 0.72 to 1.45 (p = 0.909). The mean systolic and
      diastolic blood pressure values were not significantly different across the three
      genotypic groups, between hypertensives and normotensives, or when stratified by
      gender. Despite having a similar minor allele frequency (MAF) of 14.5% compared
      with the SMILE cohort, our results did not support an association of the mirSNP
      rs11174811 with the hypertension phenotype or with continuous blood pressure
      outcomes in the south Indian population.

PMID- 29182375
TI  - Multilevel Examination of Job Satisfaction and Career Intentions of Collegiate
      Athletic Trainers: A Quantitative Approach.
AB  - CONTEXT:   Recent employment data from collegiate athletic training settings have
      demonstrated departure trends among men and women. These trends have been
      hypothesized to be related to work-life balance. However, work-life balance is
      only 1 aspect of a myriad of factors. Due to the complex nature of the work-life
      interface, a multilevel examination is needed to better understand the
      precipitators of departure. OBJECTIVE:   To quantitatively examine factors that
      may influence collegiate athletic trainers' (ATs') job satisfaction and career
      intentions via a multilevel examination of the work-life interface. DESIGN:  
      Cross-sectional study. SETTING:   Web-based questionnaire. PATIENTS OR OTHER
      PARTICIPANTS:   Athletic trainers employed in National Collegiate Athletic
      Association Division I, II, or III or National Association of Intercollegiate
      Athletics colleges or universities (N = 299: 56.5% female, 43.5% male). The
      average age of participants was 33.6 +/- 8.3 years, and their average experience
      was 10.3 +/- 7.6 years. DATA COLLECTION AND ANALYSIS:   Participants responded to
      an online questionnaire consisting of demographic questions, 9 Likert-scale
      surveys, and open-ended questions. Job-satisfaction Scores (JSSs) and intention
      to-leave scores (ITLSs) served as the dependent variables and factors from
      individual, organizational, and sociocultural levels were the independent
      variables. Hierarchical regression analysis was run to determine the
      predictability of factors. RESULTS:   No sex differences in ITLS or JSS were
      found in our sample. Independent variables explained 68.5% of the variance in JSS
      and 28.8% of the variance in ITLS. Additions of factor levels increased the
      percentage of explained variance in both scores. CONCLUSIONS:   A combination of
      individual-, organizational-, and sociocultural-level factors was able to best
      predict JSS and ITLS among collegiate ATs.

PMID- 29182376
TI  - Perceptions of Work-Life Balance Practices Offered in the Collegiate Practice
      Setting.
AB  - CONTEXT:   Organizational factors have been identified as barriers to finding
      work-life balance (WLB) in athletic training. Despite the existence of
      organizational policies to address WLB, little is known about athletic trainers'
      (ATs') awareness of these policies that could assist them. OBJECTIVE:   To better
      understand the perceptions of ATs regarding the workplace practices available to
      them, which may help them achieve WLB. DESIGN:   Phenomenologic study. SETTING:  
      Collegiate practice setting. PATIENTS OR OTHER PARTICIPANTS:   Twenty-one ATs
      (women = 10, men = 11) employed at the collegiate level (National Collegiate
      Athletic Association Division I = 12, Division II = 5, Division III = 4)
      volunteered for our study. The average age of the participants was 33 +/- 9
      years. Saturation of the data was met at n = 21. DATA COLLECTION AND ANALYSIS:  
      Participants completed an in-depth, 1-on-1 phone interview, which was then
      transcribed verbatim. Data were analyzed using a phenomenologic approach.
      Credibility was determined by member checks, peer review, and researcher
      triangulation. RESULTS:   Our analyses revealed that participants (1) had a
      limited awareness of formal policies that were offered within their university or
      collegiate infrastructure; (2) used informal policies to manage their personal,
      family, and work obligations; and (3) thought that more formal policies, such as
      adherence to adequate staffing patterns and work schedules, could help establish
      WLB within collegiate athletic training settings. CONCLUSIONS:   Informal
      workplace policies were more commonly used by our participants and were viewed as
      a means of creating a supportive atmosphere. Administrators and supervisors
      should consider creating or endorsing more formal policies specific to the
      demands of an AT in the collegiate setting to help with WLB.

PMID- 29182377
TI  - Molecular landscape of pancreatic cancer: challenges and clinical implications.

PMID- 29182379
TI  - Prevalence and association of oral candidiasis with dysphagia in individuals with
      acquired brain injury.
AB  - OBJECTIVE: To describe the prevalence of oral candidiasis (OC) in individuals
      with acquired brain injury (ABI) and to evaluate the association of OC with
      improvement in dysphagia. DESIGN: Longitudinal observational study. METHODS:
      Individuals with ABI admitted to rehabilitation were recruited over a one-year
      period (n = 206 (59% with dysphagia)). OC-data were collected by clinical
      examinations and verified by cultivation/microscopy in every 3 weeks during first
      10 weeks of admission. Dysphagia improvement was defined by: 1) first positive
      change in food consistency, 2) initiation of at least soft food consistency.
      Individuals with/without OC were compared using multivariable Cox proportional
      hazards regression. RESULTS: The overall OC prevalence in all individuals, in
      individuals with dysphagia and in individuals not treated with antifungal agents
      were 32.5%, 43.4% and 29.7%, respectively. The OC prevalence was 24.8% at one
      week after admission and reduced to 10.1% ten weeks after admission. Adjusted
      hazard ratios for improvement in dysphagia were 0.64-0.77 in OC compared to
      without OC, though not statistically significant. CONCLUSION: Prevalence of OC
      was high at admission but reduced during rehabilitation. Though non-significant,
      the negative trend between OC and improvement in dysphagia suggest that OC may
      delay rehabilitation of dysphagia.

PMID- 29182380
TI  - The Relationship between Emotional and Esteem Social Support Messages and Health.
AB  - The purpose of this investigation is to determine the relative contribution of
      five types of social support to improved patient health. This analysis suggests
      that emotional and esteem social support messages are associated with improved
      patient health as measured by a decrease in average blood glucose levels among
      diabetic patients. In addition, when two system feature variables, two system use
      variables, two measures of learning, one measure of self-efficacy, and one
      measure of affect toward their HCP were added to the baseline model, a third
      significant factor emerged. Perceptions about learning about diabetes from
      reading the digital messages sent by their HCP also predicted improved patient
      health. Cognitive-Emotional Theory of Esteem Support Messages suggests a
      combination of esteem social support and emotional social support messages
      enhanced our ability to predict improved patient health by change in patient
      hemoglobin A1c (HbA1c) scores. While a nonrandomized prospective study, this
      investigation provides support for the notion that provider-patient interaction
      is related to improved patient health and that both emotional and esteem social
      support messages play a role in that process. Finally, the study suggests some
      types of social support are and other types are not associated with improved
      patient health; this is consistent with the optimal matching hypothesis.

PMID- 29182378
TI  - Early changes in cerebral autoregulation among youth hospitalized after sports
      related traumatic brain injury.
AB  - OBJECTIVE: To examine early cerebral haemodynamic changes among youth
      hospitalized with sports-related traumatic brain injury (TBI). STUDY DESIGN:
      Youth 0-18 years admitted to a level one trauma centre with sports-related TBI
      were enrolled. Daily measures included clinical symptoms and Glasgow Coma Scale
      (GCS) score. Using Transcranial Doppler (TCD) ultrasonography and tilt testing,
      we measured middle cerebral artery flow velocity (Vmca) and cerebral
      autoregulation index (ARI). RESULTS: Six previously healthy males age 14 (IQR 12
      16) years with headache and abnormal head CT were admitted with median admission
      GCS 15. Six patients underwent 12 TCD examinations between hospital days 0-9. Low
      Vmca occurred in 3/6 patients and on the side of TBI, whereas high Vmca occurred
      in 2/6 patients. Five patients had at least one measurement of impaired and five
      patients had absent cerebral autoregulation of at least one hemisphere; all these
      five patients had GCS 15 and headache during TCD examinations. Three patients
      were discharged with absent cerebral autoregulation. Five (83%) patients were
      discharged to home and one patient was discharged to a rehabilitation facility.
      CONCLUSION: Headache, abnormal Vmca and impaired cerebral autoregulation occur
      after sports-related TBI, despite normal GCS. Headache may signal underlying
      neurovascular abnormality in sports-related TBI.

PMID- 29182381
TI  - A validation of the Polish version of the Coma Recovery Scale-Revised (CRSR).
AB  - PRIMARY OBJECTIVE: The aim of this study was to determine the validity of the
      Polish version of the Coma Recovery Scale-Revised (CRS-R). METHODS AND DESIGN:
      Two trained raters, A and B, administered CRS-R on a group of 20 patients with
      severe brain injury (median age +/- SD, 38.0 +/- 14.39 years). Both rater A and
      rater B completed their assessment on day 1, and rater A repeated their
      assessment on day 2. Inter-rater and test-retest reliability were evaluated with
      an intra-class correlation coefficient and Spearman rank correlation. Internal
      consistency was estimated with Cronbach's alpha. Agreement in diagnostic
      impression was determined using Cohen's kappa. RESULTS: Inter-rater reliability
      for CRS-R total scores and test-retest reliability was excellent: (rho = 0.76, p
      < 0.001) and (rho = 0.92, p < 0.001), respectively. Inter-rater diagnostic
      agreement was good (kappa = 0.72, p < 0.001). Inter-rater reliability for
      subscales was fair to excellent. Internal consistency was excellent (Cronbach's
      alpha = 0.85). CONCLUSION: The Polish version of CRS-R can be administered
      reliably by trained raters and can successfully differentiate between vegetative
      state (VS), minimally conscious (MCS), and patients emerging from a minimally
      conscious state (EMCS).

PMID- 29182382
TI  - Features of the daily rhythms of blood melatonin and glucose in goats during
      different natural photoperiod.
AB  - The scope of the present study was to explore the features of the daily rhythms
      of plasma melatonin and blood glucose in goats during different natural
      photoperiod imposed by the four seasons. Five Sarda breed pluriparus female
      goats, 2 years old, with a mean body weight 40.5 +/- 2.3 kg, lead to a natural
      pasture, were cannulated the day before the start of the study for sample
      collection performed during spring and autumn equinoxes, and winter and summer
      solstices for a 48-h period. On blood samples, melatonin and glucose
      concentrations were assessed. Our results indicate a daily rhythm of both
      parameters studied which characteristics were influenced by the different
      photoperiod due to season. During the experimental period, the two parameters
      showed a negative correlation, despite the onset of melatonin concentration was
      linked to the sunset, whereas the onset and offset of glucose were not linked to
      the photoperiod. In conclusion, we can claim that the two parameters are driven
      by different entrainable systems, but further studies are necessary to establish
      their correlation.

PMID- 29182383
TI  - Ovarian cancer: how can resistance to chemotherapy be tackled?

PMID- 29182385
TI  - Magnetic resonance imaging measurements of organs within the coelomic cavity of
      red-eared sliders (Trachemys scripta elegans), yellow-bellied sliders (Trachemys
      scripta scripta), Coastal plain cooters (Pseudemys concinna floridana), and
      hieroglyphic river cooters (Pseudemys concinna hieroglyphica).
AB  - OBJECTIVE To determine anatomic reference points for 4 turtle species and to
      evaluate data on relative anatomic dimensions, signal intensities (SIs), and
      position of selected organs within the coelomic cavity by use of MRI. ANIMALS 3
      turtle cadavers (1 red-eared slider [Trachemys scripta elegans], 1 yellow-bellied
      slider [Trachemys scripta scripta], and 1 Coastal plain cooter [Pseudemys
      concinna floridana]) and 63 live adult turtles (30 red-eared sliders, 20 yellow
      bellied sliders, 5 Coastal plain cooters, and 8 hieroglyphic river cooters
      [Pseudemys concinna hieroglyphica]). PROCEDURES MRI and necropsy were performed
      on the 3 turtle cadavers. Physical examination, hematologic evaluation, and whole
      body radiography were performed on the 63 live turtles. Turtles were sedated, and
      MRI in transverse, sagittal, and dorsal planes was used to measure organ
      dimensions, position within the coelomic cavity, and SIs. Body positioning after
      sedation was standardized with the head, neck, limbs, and tail positioned in
      maximum extension. RESULTS Measurements of the heart, liver, gallbladder, and
      kidneys in sagittal, transverse, and dorsal planes; relative position of those
      organs within the coelom; and SIs of the kidneys and liver were obtained with MRI
      and provided anatomic data for these 4 turtle species. CONCLUSIONS AND CLINICAL
      RELEVANCE MRI was a valuable tool for determining the position, dimensions, and
      SIs of selected organs. Measurement of organs in freshwater chelonians was
      achievable with MRI. Further studies are needed to establish reference values for
      anatomic structures in turtles. Results reported here may serve as guidelines and
      aid in clinical interpretation of MRI images for these 4 species.

PMID- 29182384
TI  - Efficacy of a rectal spacer with prostate SABR-first UK experience.
AB  - OBJECTIVE: This study assessed the use of implanted hydrogel rectal spacers for
      stereotactic ablative radiotherapy-volumetric modulated arc therapy (SABR-VMAT)
      patients, investigating practicality, dosimetric impact, normal tissue
      complication probability (NTCP) and early toxicity. METHODS: Data from the first
      6 patients treated within a prostate SABR and rectal spacer trial were examined
      to determine spacer insertion tolerability, resultant changes in treatment
      planning and dosimetry and early toxicity effects. CT scans acquired prior to
      spacer insertion were used to generate SABR plans which were compared to post
      insertion plans. Plans were evaluated for target coverage, conformity, and organs
      at risk doses with NTCPs also determined from resultant dose fluences. Early
      toxicity data were also collected. RESULTS: All patients had successful spacer
      insertion under local anaesthetic with maximal Grade 1 toxicity. All plans were
      highly conformal, with no significant differences in clinical target volume dose
      coverage between pre- and post-spacer plans. Substantial improvements in rectal
      dose metrics were observed in post-spacer plans, e.g. rectal volume receiving 36
      Gy reduced by >=42% for all patients. Median NTCP for Grade 2 + rectal bleeding
      significantly decreased from 4.9 to 0.8% with the use of a rectal spacer (p =
      0.031). To date, two episodes of acute Grade 1 proctitis have been reported
      following treatment. CONCLUSION: The spacer resulted in clinically and
      statistically significant reduction in rectal doses for all patients. Advances in
      knowledge: This is one of the first studies to investigate the efficacy of a
      hydrogel spacer in prostate SABR treatments. Observed dose sparing of the rectum
      is predicted to result in meaningful clinical benefit.

PMID- 29182386
TI  - In vivo evaluation of effects of sedation on results of acoustoelastography of
      the superficial digital flexor tendons in clinically normal horses.
AB  - OBJECTIVE To assess the effects of sedation on results of acoustoelastography of
      the superficial digital flexor tendons (SDFTs) in clinically normal horses.
      ANIMALS 27 clinically normal horses. PROCEDURES For each horse, the pathology
      index (PI) for the SDFT of each thoracic limb was determined by use of
      acoustoelastography at 4 locations (5, 10, 15, and 20 cm distal to the accessory
      carpal bone). Horses were evaluated before and after they were sedated with a
      combination of detomidine hydrochloride (0.01 mg/kg, IV) and butorphanol tartrate
      (0.01 mg/kg, IV). A repeated-measures ANOVA was used for statistical analysis.
      RESULTS Overall, the PI was lower after sedation than before sedation. In
      addition, the PI was lower at more distal locations than at more proximal
      locations. There was not a significant effect of limb (left or right).
      Differences among individual horses accounted for the largest variance effect.
      CONCLUSIONS AND CLINICAL RELEVANCE Sedation with detomidine and butorphanol
      facilitated acoustoelastography; however, it decreased the SDFT PI in clinically
      normal horses and should be used consistently in prospective studies. Variance
      associated with each individual horse in the sample population had the greatest
      effect on the PI.

PMID- 29182388
TI  - Pharmacokinetics of ampicillin-sulbactam in serum and synovial fluid samples
      following regional intravenous perfusion in the distal portion of a hind limb of
      adult cattle.
AB  - OBJECTIVE To describe concentration-over-time data for ampicillin and sulbactam
      in the digital and systemic circulations and synovial fluid (SYN) of cattle
      following a single injection of ampicillin-sulbactam as a regional IV perfusion
      (RIVP). ANIMALS 6 healthy adult nonlactating Jersey-crossbred cows. PROCEDURES
      The right hind limb of each cow was aseptically prepared. A tourniquet was
      applied around the midmetatarsal region, and 1.0 g of ampicillin with 0.5 g of
      sulbactam in a combined formulation was administered as an RIVP into the dorsal
      common digital vein (DCDV). Blood samples from the DCDV and jugular vein and SYN
      samples from the metatarsophalangeal joint of the prepared limb were collected
      immediately before and at predetermined times for 24 hours after RIVP. One blood
      sample was obtained from the abaxial proper plantar vein of the lateral digit of
      the prepared limb 0.25 hours after RIVP. Serum and SYN ampicillin and sulbactam
      concentrations were determined by high-performance liquid chromatography. RESULTS
      Mean +/- SD maximum concentration of ampicillin in SYN and serum obtained from
      the abaxial proper plantar and jugular veins was 1,995 +/- 1,011 MUg/mL, 5,422 +/
      1,953 MUg/mL, and 2.5 +/- 1.6 MUg/mL, respectively. Corresponding serum and SYN
      concentrations of sulbactam were lower but followed the same pattern over time as
      those for ampicillin. Synovial fluid ampicillin concentration remained above 8
      MUg/mL for a mean time of 18.9 hours. CONCLUSIONS AND CLINICAL RELEVANCE
      Potentially therapeutic concentrations of ampicillin were achieved in regional
      serum and SYN samples; SYN concentrations remained at potentially therapeutic
      values for > 12 hours following RIVP of 1.5 g of ampicillin-sulbactam in the hind
      limb of healthy cows.

PMID- 29182389
TI  - Effect of a high-fat-high-cholesterol diet on gallbladder bile acid composition
      and gallbladder motility in dogs.
AB  - OBJCTIVE To investigate the effects of dietary lipid overload on bile acid
      metabolism and gallbladder motility in healthy dogs. ANIMALS 7 healthy Beagles.
      PROCEDURES In a crossover study, dogs were fed a high-fat-high-cholesterol diet
      (HFCD) or a low-fat diet (LFD) for a period of 2 weeks. After a 4-month washout
      period, dogs were fed the other diet for 2 weeks. Before and at the end of each
      feeding period, the concentrations of each of the gallbladder bile acids,
      cholecystokinin (CCK)-induced gallbladder motility, and bile acid metabolism
      related hepatic gene expression were examined in all dogs. RESULTS The HFCD
      significantly increased plasma total cholesterol concentrations. The HFCD also
      increased the concentration of taurochenodeoxycholic acid and decreased the
      concentration of taurocholic acid in bile and reduced gallbladder contractility,
      whereas the LFD significantly decreased the concentration of taurodeoxycholic
      acid in bile. Gene expression analysis revealed significant elevation of
      cholesterol 7alpha-hydroxylase mRNA expression after feeding the HFCD for 2
      weeks, but the expression of other genes was unchanged. CONCLUSIONS AND CLINICAL
      RELEVANCE Feeding the HFCD and LFD for 2 weeks induced changes in gallbladder
      bile acid composition and gallbladder motility in dogs. In particular, feeding
      the HFCD caused an increase in plasma total cholesterol concentration, an
      increase of hydrophobic bile acid concentration in bile, and a decrease in
      gallbladder sensitivity to CCK. These results suggested that similar bile acid
      compositional changes and gallbladder hypomotility might be evident in dogs with
      hyperlipidemia.

PMID- 29182390
TI  - In vitro effect of blood cell counts on multiple-electrode impedance aggregometry
      in dogs.
AB  - OBJECTIVE To assess the effect of decreased platelet and WBC counts on platelet
      aggregation as measured by a multiple-electrode impedance aggregometer in dogs.
      ANIMALS 24 healthy dogs. PROCEDURES From each dog, 9 mL of blood was collected
      into a 10-mL syringe that contained 1 mL of 4% sodium citrate solution to yield a
      10-mL sample with a 1:9 citrate-to-blood ratio. Each sample was then divided into
      unmanipulated and manipulated aliquots with progressively depleted buffy-coat
      fractions such that 2 to 3 blood samples were evaluated per dog. The Hct for
      manipulated aliquots was adjusted with autologous plasma so that it was within 2%
      of the Hct for the unmanipulated aliquot for each dog. All samples were analyzed
      in duplicate with a multiple-electrode impedance aggregometer following the
      addition of ADP as a platelet agonist. The respective effects of platelet count,
      plateletcrit, Hct, and WBC count on platelet aggregation area under the curve
      (AUC), aggregation, and velocity were analyzed with linear mixed models. RESULTS
      WBC count was positively associated with platelet AUC, aggregation, and velocity;
      blood samples with leukopenia had a lower AUC, aggregation, and velocity than
      samples with WBC counts within the reference range. Platelet count, plateletcrit,
      and Hct did not have an independent effect on AUC, aggregation, or velocity.
      CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that WBC count was
      positively associated with platelet aggregation when ADP was used to activate
      canine blood samples for impedance aggregometry. That finding may be clinically
      relevant and needs to be confirmed by in vivo studies.

PMID- 29182391
TI  - Effect of meloxicam administration on movement, feeding, and drinking behaviors
      of transported and nontransported cattle.
AB  - OBJECTIVE To evaluate the effects of meloxicam on movement, feeding, and drinking
      behaviors of transported and nontransported cattle. ANIMALS 100 crossbred beef
      steers. PROCEDURES During experiment 1 of a 2-experiment study, calves from a
      livestock auction received meloxicam (1 mg/kg, PO; n = 50) or a lactose placebo
      (1 capsule/calf; 50; control), then calves were transported approximately 1,000
      km overnight to a feedlot, where they were instrumented with a real-time location
      monitoring ear tag, placed in randomly assigned pens (n = 5 pens/treatment), and
      monitored for 21 days. During experiment 2, calves in pens were administered the
      treatment opposite that of experiment 1, returned to their pens without
      undergoing transportation, and monitored for another 21 days. For each
      experiment, mean daily distance traveled and percentage time spent near feed
      (PNF) and water (PNW) were calculated on a pen basis and compared between
      treatments. RESULTS During experiment 1, mean daily distance traveled, PNF, and
      PNW did not differ significantly between meloxicam-treated and control calves;
      however, all 3 behaviors varied significantly by day. During experiment 2,
      although mean distance traveled was significantly associated with the interaction
      between day and treatment, it did not differ significantly between meloxicam
      treated and control calves within any specific day. Mean PNF and PNW were
      significantly associated with day only, although no pattern in that effect was
      evident. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a single dose
      of meloxicam prior to transportation did not significantly affect the behaviors
      of transported and nontransported calves.

PMID- 29182392
TI  - Effect of oral administration of meloxicam prior to transport on inflammatory
      mediators and leukoctye function of cattle at feedlot arrival.
AB  - OBJECTIVE To investigate the effects of meloxicam administration before long
      distance transport on inflammatory mediators and leukocyte function of cattle at
      feedlot arrival. ANIMALS 60 healthy yearling beef steers. PROCEDURES Single
      source steers were assigned to a transported (n = 40) or nontransported (20)
      group. Then, half of the steers within each group were assigned to receive
      meloxicam (1 mg/kg, PO) or a lactose placebo (1 bolus/steer, PO). All steers were
      transported approximately 1,300 km overnight to a feedlot; however, the
      nontransported group was moved before treatment (meloxicam or placebo)
      administration and allowed a 17-day acclimation period, whereas the transported
      group was moved immediately after treatment administration on day -1. Blood
      samples for measurement of inflammatory mediators and leukocyte function were
      collected from all steers on days -1, 0, and 3. RESULTS For steers that received
      meloxicam, mean plasma meloxicam concentration for the transported group was
      significantly greater than that for the nontransported group on day 0. For steers
      that received the placebo, mean haptoglobin-matrix metalloproteinase-9 complex
      for the transported group was significantly greater than that for the
      nontransported group on day 0. Mean haptoglobin concentration, neutrophil L
      selectin intensity, and polymorphonuclear leukocyte count for the transported
      group were significantly greater than those for the nontransported group. Mean
      substance P concentration for nontransported steers that received meloxicam was
      significantly lower than that for the other 3 treatment groups. CONCLUSIONS AND
      CLINICAL RELEVANCE Results indicated meloxicam administration to healthy steers
      immediately before long-distance transport did not significantly mitigate the
      effects of transport-induced stress on leukocyte function or inflammatory
      markers.

PMID- 29182393
TI  - Analysis of the association between density of Helicobacter spp and gastric
      lesions in dogs.
AB  - OBJECTIVE To evaluate the correlation between the density of native gastric
      Helicobacter spp and the presence of gastric lesions in dogs. ANIMALS 80 dogs of
      various breeds, sexes, and ages. PROCEDURES Gastroscopic and histologic
      examinations were performed for all dogs. Helicobacter spp were detected by
      combining evaluation of urease activity and results of bacteriologic culture,
      microscopic observation, and a 16S rRNA PCR assay. The density of Helicobacter
      like organisms was evaluated with light microscopy by use of Warthin-Starry
      modified stain. Correlations were evaluated by use of the Spearman correlation
      analysis. RESULTS Gastritis was found in 55 of 80 dogs and classified as mild (n
      = 31), moderate (16), or severe (8). Of these 55 dogs, only 8 had clinical signs.
      Histologic examination revealed some degree of lymphocytic-plasmacytic
      infiltrate, mild eosinophilia, and neutrophilic inflammation in the lamina
      propria. Seventy-six dogs had positive results for Helicobacter spp. Helicobacter
      pylori DNA was not detected. Low density and homogeneous distribution of
      Helicobacter spp were observed in all gastric zones. CONCLUSIONS AND CLINICAL
      RELEVANCE A significant correlation between density of Helicobacter spp and
      gastroscopic or histologic lesions was not detected. These findings supported the
      contention that there is no correlation between general Helicobacter spp density
      or numbers and gastritis in dogs.

PMID- 29182394
TI  - Effects of intravenous administration of lidocaine and buprenorphine on
      gastrointestinal tract motility and signs of pain in New Zealand White rabbits
      after ovariohysterectomy.
AB  - OBJECTIVE To compare analgesic and gastrointestinal effects of lidocaine and
      buprenorphine administered to rabbits undergoing ovariohysterectomy. ANIMALS
      Fourteen 12-month-old female New Zealand White rabbits. PROCEDURES Rabbits were
      assigned to 2 treatment groups (7 rabbits/group). One group received
      buprenorphine (0.06 mg/kg, IV, q 8 h for 2 days), and the other received
      lidocaine (continuous rate infusion [CRI] at 100 MUg/kg/min for 2 days).
      Variables, including food and water consumption, fecal output, glucose and
      cortisol concentrations, and behaviors while in exercise pens, were recorded.
      RESULTS Rabbits receiving a lidocaine CRI had significantly higher
      gastrointestinal motility, food intake, and fecal output and significantly lower
      glucose concentrations, compared with results for rabbits receiving
      buprenorphine. Rabbits receiving lidocaine also had a higher number of normal
      behaviors (eg, sprawling, traveling, and frolicking) after surgery, compared with
      behaviors such as crouching and sitting that were seen more commonly in rabbits
      receiving buprenorphine. Both groups had significant weight loss after surgery.
      Pain scores did not differ significantly between treatment groups. Significant
      decreases in heart rate and respiratory rate were observed on the day of surgery,
      compared with values before and after surgery. Rabbits in the lidocaine group had
      significantly overall lower heart rates than did rabbits in the buprenorphine
      group. CONCLUSIONS AND CLINICAL RELEVANCE A CRI of lidocaine to rabbits provided
      better postoperative outcomes with respect to fecal output, food intake, and
      glucose concentrations. Thus, lidocaine appeared to be a suitable alternative to
      buprenorphine for alleviating postoperative pain with minimal risk of anorexia
      and gastrointestinal ileus.

PMID- 29182395
TI  - Evaluation of the dens-to-axis length ratio and dens angle in toy-breed dogs with
      and without atlantoaxial instability and in healthy Beagles.
AB  - OBJECTIVE To evaluate and compare morphological characteristics of the dens in
      atlantoaxial instability (AAI)-predisposed toy-breed dogs (TBDs) with and without
      AAI and non-AAI-predisposed healthy Beagles. ANIMALS 80 AAI-affected and 40
      nonaffected TBDs and 40 Beagles. PROCEDURES Each dog underwent CT examination of
      the cervical vertebral column. On median 3-D multiplanar reconstruction images,
      the dens angle (DA) was measured as were the lengths of the dens and the body of
      the axis; the dens-to-axis length ratio (ratio of the dens length to the axis
      body length [DALR]) was calculated. Data were compared among dog groups. RESULTS
      The DALR in nonaffected TBDs and Beagles did not differ significantly. The mean
      DALR for AAI-affected TBDs was significantly lower than that for nonaffected
      TBDs. The mean DA of AAI-affected TBDs was significantly greater than that of
      Beagles and nonaffected TBDs. CONCLUSIONS AND CLINICAL RELEVANCE Results
      indicated that a low DALR might be associated with a high probability of dens
      abnormalities in TBDs. Additionally, dens length in AAI-affected TBDs appeared to
      be smaller than that in non-AAI-affected TBDs, given the low DALR in AAI-affected
      TBDs. Further investigations to determine reference ranges of the DA and DALR and
      the potential usefulness of those variables as diagnostic markers for AAI in TBDs
      are warranted.

PMID- 29182396
TI  - Effect of bilateral ventriculocordectomy via ventral laryngotomy on laryngeal
      airway resistance in larynges of canine cadavers.
AB  - OBJECTIVE To evaluate the effect of bilateral ventriculocordectomy via ventral
      laryngotomy on laryngeal airway resistance (LAR) in canine cadaver larynges.
      SAMPLE 6 clinically normal canine cadaver larynges. PROCEDURES LAR was determined
      for each specimen before (baseline) and after bilateral ventriculocordectomy with
      the epiglottis open and closed. After ventral laryngotomy was performed, the
      vocal cords were sharply excised, and the incised mucosal edges were apposed with
      4-0 glycomer 631 suture in a simple continuous pattern. The thyroid cartilage was
      apposed with 3-0 polypropylene suture in a simple continuous pattern. RESULTS
      With the epiglottis closed, baseline median LAR was 27.6 cm H2O/L/s (range, 21.2
      to 30.6 cm H2O/L/s), which did not differ significantly from the median LAR after
      bilateral ventriculocordectomy (24.7 cm H2O/L/s [range, 20.6 to 27.7 cm
      H2O/L/s]). With the epiglottis open, baseline median LAR was 7.3 cm H2O/L/s
      (range, 5.4 to 7.8 cm H2O/L/s), which did not differ significantly from the
      median LAR after bilateral ventriculocordectomy (7.2 cm H2O/L/s [range, 6.6 to
      7.6 cm H2O/L/s]). CONCLUSIONS AND CLINICAL RELEVANCE Bilateral
      ventriculocordectomy did not affect LAR with an open epiglottis in canine cadaver
      larynges. Therefore, it may not be an effective treatment for laryngeal
      paralysis. It also did not affect LAR with a closed epiglottis, which may
      indicate protection against aspiration pneumonia.

PMID- 29182399
TI  - Application of camelid heavy-chain variable domains (VHHs) in prevention and
      treatment of bacterial and viral infections.
AB  - Camelid heavy-chain variable domains (VHHs) are the smallest, intact, antigen
      binding units to occur in nature. VHHs possess high degrees of solubility and
      robustness enabling generation of multivalent constructs with increased avidity -
      characteristics that mark their superiority to other antibody fragments and
      monoclonal antibodies. Capable of effectively binding to molecular targets
      inaccessible to classical immunotherapeutic agents and easily produced in
      microbial culture, VHHs are considered promising tools for pharmaceutical
      biotechnology. With the aim to demonstrate the perspective and potential of VHHs
      for the development of prophylactic and therapeutic drugs to target diseases
      caused by bacterial and viral infections, this review article will initially
      describe the structural features that underlie the unique properties of VHHs and
      explain the methods currently used for the selection and recombinant production
      of pathogen-specific VHHs, and then thoroughly summarize the experimental
      findings of five distinct studies that employed VHHs as inhibitors of host
      pathogen interactions or neutralizers of infectious agents. Past and recent
      studies suggest the potential of camelid heavy-chain variable domains as a novel
      modality of immunotherapeutic drugs and a promising alternative to monoclonal
      antibodies. VHHs demonstrate the ability to interfere with bacterial pathogenesis
      by preventing adhesion to host tissue and sequestering disease-causing bacterial
      toxins. To protect from viral infections, VHHs may be employed as inhibitors of
      viral entry by binding to viral coat proteins or blocking interactions with cell
      surface receptors. The implementation of VHHs as immunotherapeutic agents for
      infectious diseases is of considerable potential and set to contribute to public
      health in the near future.

PMID- 29182397
TI  - Breast tissue density change after oophorectomy in BRCA mutation carrier patients
      using visual and volumetric analysis.
AB  - OBJECTIVE: BRCA1/2 mutations account for 30-50% of hereditary breast cancers and
      bilateral oophorectomy is associated with a reduced risk of breast cancer in
      these patients. Breast density is a well-established breast cancer risk factor
      and is also associated with increased risk in BRCA carriers. The aim of the study
      was to evaluate the impact of oophorectomy on mammographic breast density and to
      assess which method of breast density assessment is more sensitive to change over
      time. METHODS: Retrospective study of 50 BRCA1/2 patients who underwent bilateral
      oophorectomy and had at least a baseline and post-surgery mammogram. Mammographic
      breast density was determined by Volpara and consensus visual assessment by two
      radiologists. The primary endpoint was change in density between baseline and the
      first mammogram post-surgery. RESULTS: At baseline, there was a non-significant
      trend for decreased density with increasing age. Volumetric breast density (VBD)
      significantly decreased after oophorectomy from a median VBD of 12.5% at baseline
      to 10.2% post-surgery which was driven by a reduction in fibroglandular volume.
      There was a higher absolute decrease in VBD in patients aged between 40-50 (p <
      0.01). Using Volpara Density Grades (analogous to BI-RADS 4th edition density
      categories), 84% of females displayed a decrease in density category over the
      study period compared to only 76% using the radiologists' visual classification
      (p < 0.001) Conclusion: Oophorectomy is associated with a decrease in breast
      density and younger patients exhibit a larger absolute decrease. Volpara is more
      sensitive to identify change over time compared to visual assessment. Advances in
      knowledge: Oophorectomy is associated with a significant decrease in VBD in
      patients with BRCA mutations and Volpara Density Grades were more sensitive to
      identify decreases in density compared to visually assessed BI-RADS categories.
      Decreases in breast density following oophorectomy surgery in BRCA patients may
      be one of the mechanisms contributing to the observed decreased breast cancer
      risk after surgery. However, further studies are needed to investigate the
      relationship between breast density, oophorectomy and breast cancer risk in BRCA
      patients.

PMID- 29182401
TI  - The Association of Cataract and Lens Epithelial Cell Apoptosis in Patients with
      Pseudoexfoliation Syndrome.
AB  - PURPOSE: The aim of this study was to measure the density of apoptotic lens
      epithelial cells (LECs) and to determine its association with cataract formation
      in eyes with pseudoexfoliation syndrome (PEX). MATERIALS AND METHODS: Twenty-one
      eyes of 21 patients diagnosed with PEX without glaucoma (Group 1) and 22 eyes of
      22 subjects without PEX (Group 2) were enrolled in this study. During cataract
      surgery, anterior capsule samples were obtained by the 5.5 mm continuous
      curvilinear capsulorhexis method. Apoptosis was determined with a TUNEL kit
      (Boster, Wuhan, China) according to the manufacturer's protocol. Four fields in
      each pathology preparation were chosen randomly under a microscope, and 100 cells
      were counted in each field to calculate the apoptosis rates. RESULTS: Forty-three
      eyes of 43 subjects were enrolled in this study. There were no significant
      differences in age or sex between the two studied groups (p > 0.05). Under a
      microscope, the LECs were stained light blue and their nuclei were oval shaped.
      Positive stained cells were found occasionally in Group 2, while a significant
      amount of black-brown positively stained LECs with condensed nuclei was found in
      Group 1. The apoptosis rates were 35.2 +/- 2.1% and 14.1 +/- 1% in Groups 1 and
      2, respectively. The proportion of positively stained LECs was higher in Group 1
      (p < 0.001). CONCLUSION: Our study suggests that apoptosis in LECs is the
      pathophysiological mechanism for the higher rate of cataracts in PEX patients, in
      addition to the ocular ischemia hypothesis.

PMID- 29182400
TI  - Interleukin-4 Gene Intron 3 VNTR Polymorphism in Type 2 Diabetes Patients with
      Peripheral Neuropathy.
AB  - OBJECTIVE: Diabetic peripheral neuropathy (DPN) is one of late complications of
      diabetes mellitus. The aim of this study was to evaluate the association between
      variable number tandem repeat (VNTR) polymorphism in intron 3 of interleukin-4
      gene and risk of DPN. METHODS: We examined 926 T2DM patients and 420 healthy
      controls. In the patient group, 44% had DPN. Genomic DNA was isolated from all
      subjects and genotyped for the IL-4 VNTR polymorphism by polymerase chain
      reaction (PCR). RESULTS: No significant difference was observed in the frequency
      of minor P1 allele between T2DM patients and controls (OR 1.00, 95% CI 0.81-1.23,
      p = 0.988). The distribution of IL-4 VNTR polymorphism was compared between
      patients with DPN and those without it. The polymorphism was not significantly
      associated with DPN in studied subjects. In comparison of 406 T2DM patients with
      DPN and 520 patients without it, the OR (95% CI) for P1 allele was 0.82 (0.65
      1.04), p = 0.10 and for P1P1 genotype 1.00 (0.53-1.89), p = 0.991. When two
      subgroups of patients with DPN, those with cardiovascular disease (CVD) and
      without CVD, were compared, subgroup with coexisting CVD had significantly higher
      frequency of P1 allele than patients without CVD, with odds ratio for the P1
      allele 3.27 (95% CI 1.83-5.83), p = 0.0001. CONCLUSION: Our results demonstrated
      that VNTR polymorphism in the IL-4 gene is associated with DPN in type 2 diabetes
      patients with coexisting CVD.

PMID- 29182403
TI  - Long-Distance Triathletes' Intentions to Manipulate Energy and Macronutrient
      Intake Over a Training Macrocycle.
AB  - This study explored the information sources long-distance triathletes used to
      inform their training and nutrition plans, and evaluated these plans over a
      training macrocycle. Seventy-four long-distance triathletes completed the online
      survey. Coaches were the most popular training information source (69%), whereas
      nonprofessional sources (internet 65%, other athletes 53%) were more popular than
      nutritionists (29%) for nutrition information. Attributes valued most in an
      information source were: source prior personal experience, individualized advice,
      breadth of knowledge, and credibility. Sixty-five percent of participants
      reported previously manipulating dietary intake to improve performance. Forty
      three percent reported carbohydrate loading previously, but only 29% planned to
      carbohydrate load for their upcoming event. Thirty-six percent of participants
      planned to reduce carbohydrate intake at some point in training, predominantly
      early (28%) and toward the end (22%) of their macrocycles. Twenty percent of
      participants planned to maintain energy intake early, and increase (14%) or
      maintain energy intake (15%) mid-cycle. Triathletes' training plans showed
      intentions for concurrent increases in volume and intensity, rather than a
      classical periodized training progression. Limitations of this study include the
      lack of diet intake and training data, quantitative comparison with dietary
      guidelines and high/low carbohydrate classification, and an overrepresentation of
      women in the study cohort. This research showed the popularity of the internet
      and other athletes to inform triathletes' nutrition plans, and revealed
      intentions to reduce carbohydrate intakes alongside training load increases,
      contrary to professional guidelines. Understanding athletes' intentions and
      sources of nutrition information is crucial to developing effective nutrition
      education strategies.

PMID- 29182402
TI  - Individual versus interprofessional team performance in formulating care
      transition plans: A randomised study of trainees from five professional groups.
AB  - Health professions trainees' performance in teams is rarely evaluated, but
      increasingly important as the healthcare delivery systems in which they will
      practice move towards team-based care. Effective management of care transitions
      is an important aspect of interprofessional teamwork. This mixed-methods study
      used a crossover design to randomise health professions trainees to work as
      individuals and as teams to formulate written care transition plans. Experienced
      external raters assessed the quality of the written care transition plans as well
      as both the quality of team process and overall team performance. Written care
      transition plan quality did not vary between individuals and teams (21.8 vs.
      24.4, respectively, p = 0.42). The quality of team process did not correlate with
      the quality of the team-generated written care transition plans (r = -0.172, p =
      0.659). However, there was a significant correlation between the quality of team
      process and overall team performance (r = 0.692, p = 0.039). Teams with highly
      engaged recorders, performing an internal team debrief, had higher-quality care
      transition plans. These results suggest that high-quality interprofessional care
      transition plans may require advance instruction as well as teamwork in
      finalising the plan.

PMID- 29182404
TI  - Evaluation of the Effect of Everolimus on Retinal Pigment Epithelial Cells and
      Experimental Proliferative Vitreoretinopathy.
AB  - PURPOSE: Failure of retinal detachment surgery is most commonly due to the
      development of proliferative vitreoretinopathy (PVR). Everolimus is an inhibitor
      of mammalian target of rapamycin (mTOR), and is available as oral tablets. In
      this study, we investigated the effect of everolimus on retinal pigment
      epithelial cells and modification of the severity of experimental PVR. METHODS:
      In our in vitro studies, primary culture of retinal pigment epithelium (RPE)
      cells was obtained from pigmented Rex rabbits. Cell proliferation was assayed
      with the tetrazolium dye cytotoxicity test, and cell migration assay was
      performed in 24-well transwell units with 8-MUm filters. In the in vivo study,
      pigmented Rex rabbits weighing between 2 and 2.5 kg were used. Each rabbit eye
      underwent gas compression; one week later, 5 * 104 RPE cells were injected into
      the vitreous cavity to induce PVR, and each eye was graded with indirect
      ophthalmoscopy on days 1, 3, 7, 14, 21, and 28. The rabbits were administered
      everolimus (0.5 mg/day orally) from the day of PVR induction. Total proteins
      extracted from RPE cells and dissected retinal samples were processed for Western
      blotting analysis of mTOR and ribosomal protein S6 (RPS6). RESULTS: The in vitro
      studies showed that everolimus significantly inhibited the proliferation of RPE
      cells at 0.1 MUg/ml; additionally, at 10 MUg/ml, it suppressed the migration of
      RPE cells and significantly suppressed the expression of mTOR and RPS6 in RPE
      cells. The in vivo study did not show any benefit of oral everolimus (0.5 mg/day)
      in suppressing experimental PVR. Thus, everolimus significantly suppressed the
      expression of mTOR and RPS6 in PVR. CONCLUSIONS: Everolimus suppressed the
      proliferation and migration of RPE cells in vitro. Oral everolimus (0.5 mg/day)
      suppressed the expression of mTOR and RPS6 in the retina, but showed no effect in
      suppressing experimental PVR.

PMID- 29182405
TI  - Decrease in the Frequency of Circulating CD56+CD161+ NK Cells in Human Visceral
      Leishmaniasis.
AB  - BACKGROUND: Natural Killer (NK) cell plays an important role in the innate immune
      system and is known to produce IFN-gamma at an early stage of infection that is
      essential to eliminate intracellular infection like Leishmania spp. It is already
      established that Leishmania parasite inhibits the activity of NK cells, avoiding
      the encounter with the early innate immune response. This, in turn, favors
      establishment and further dissemination of the infection. METHODS: In the present
      study, we have tried to measure the frequency of different phenotypic subsets of
      NK cells among visceral leishmaniasis (VL) patients. RESULTS: We have phenotyped
      three distinct three distinct subsets (CD56-CD161+, CD56+CD161-, and CD56+CD161+)
      of NK (CD3-) cell using their specific markers CD161 and CD56. CONCLUSION:
      Interestingly, we observed selective loss of CD56+CD161+ subset of circulating NK
      (CD3-) cells. Importantly, the other subsets (i.e., CD56-CD161+ and CD56+CD161-)
      of circulating NK cells remain unaffected as compared with healthy subjects.

PMID- 29182406
TI  - Assessing quality of care through client satisfaction at an interprofessional
      student-run free clinic.
AB  - Student-run free clinics (SRFCs) have become important contributors not only to
      improve access to primary-care services for homeless and uninsured populations
      but also to enhance health sciences student education. In order for SRFCs to
      reliably provide high quality healthcare services and educationally benefit
      students, it is imperative to assess client perceptions of the quality of care
      provided. The objective of this study was to evaluate the delivery of healthcare
      services through a client satisfaction questionnaire at the University of
      California, Los Angeles Mobile Clinic Project (UCLA MCP). From 2012 to 2015, 194
      questionnaires that addressed demographic information, satisfaction with services
      and client outcomes were analysed. Satisfaction scores were evaluated on a four
      point scale and differences in the composite satisfaction scores were assessed
      using Mann-Whitney U-tests. Half (50%) of the client respondents report that UCLA
      MCP is their primary source of health care (MCP primary care clients), while
      81.3% reported that the clinic improved access to other healthcare resources.
      Overall, clients are highly satisfied with their experiences (Range: 3.5-3.9) and
      62% have recommended our services to others. While MCP primary-care clients
      report significantly higher satisfaction scores than non-primary-care clients on
      average (p < 0.01), the mean composite scores for all subgroups are consistently
      high. The UCLA MCP clients perceive the clinic to provide high-quality healthcare
      services. This article presents a framework that may help other SRFCs evaluate
      clients' perception of the quality of their care, an essential building block for
      effective physician-client relationships.

PMID- 29182408
TI  - Rapid Weight Loss Is Not Associated With Competitive Success in Elite Youth
      Olympic-Style Boxers in Europe.
AB  - PURPOSE: To examine the influence of rapid weight loss (RWL) on competitive
      success in elite youth Olympic-style boxers. In addition, this study examined the
      practice and prevalence of weight reduction, weight-management protocols, and
      related symptoms in youth boxers from 12 European countries (N = 83, all males,
      mean [SD] age 17.1 [0.9] y). METHODS: The data were collected using an extensive
      questionnaire on weight cutting and its associated protocols and symptoms prior
      to highest-level continental championships. Competition results were obtained at
      follow-up using a dichotomous variable: medal winning vs nonwinning at the
      European Championships. RESULTS: Binary logistic regression analysis indicated
      that "boxing experience" was significantly related to the criterion competitive
      outcome (odds ratio = 1.33; 95% confidence interval, 1.06-1.66; Nagelkerke R2 =
      .11), with a higher likelihood of competitive success for more-experienced
      boxers. Of all the youth boxers, only 25% were included in the RWL group,
      irrespective of their weight-class stratification. More than 45% of all the youth
      boxers self-reported the simultaneous combination of different weight-cutting
      methods that are known to be serious health hazards. Finally, 33% of the boxers
      experienced muscle weakness as a consequence of RWL. CONCLUSIONS: Our study
      provided evidence of pathogenic weight-management protocols that are widely
      adopted by youth boxers, and yet the present outcomes showed that RWL did not
      translate into competitive success in these elite Olympic-style boxers in Europe.
      Therefore, the authors suggest a mandatory educational program that should
      simultaneously target all the mentioned issues including both health- and
      performance-threatening consequences.

PMID- 29182407
TI  - Metformin is associated with reduced cell proliferation in human endometrial
      cancer by inbibiting PI3K/AKT/mTOR signaling.
AB  - Metformin recently gained traction as potential anti-endometrial cancer agent for
      its new applications. However, the underlying mechanisms of the anti-cancer
      effect of metformin in the endometrial cancer have not yet been fully elucidated.
      Sixty-five patients diagnosed as endometrial carcinoma were grouped into (n = 33)
      and non-treatment mixed (n = 32) for analysis. Thirty healthy donors were
      recruited as controls. We attempt to investigate the effect of metformin on Ki
      67, PI3K, p-AKT, p-S6K1, and p-4EBP1 staining in human endometrial cancer by
      immunohistochemical staining. We found that increased Ki-67 expression in women
      with endometrial cancer, which were reversed by conventional anti-diabetic doses
      of metformin in present work. In parallel, the reduced PI3K, p-AKT, p-S6K1, and p
      4EBP1 staining induced by metformin appeared to play an important role for the
      anti-proliferative effects of metformin in endometrial cancer patients. Metformin
      significantly decreased proliferation in human endometrial cancer may by
      inhibiting PI3K/AKT/mTOR signaling. Our present results add to the growing body
      of evidence supporting metformin as a potential anti-cancer agent in endometrial
      cancer.

PMID- 29182409
TI  - Association between HLA-DQB1 polymorphisms and pemphigus vulgaris: A meta
      analysis.
AB  - OBJECTIVE: This study was performed to systematically summarize the results on
      the association of HLA-DQB1 polymorphisms with pemphigus vulgaris (PV) and other
      related factors. METHODS: A comprehensive literature search of PubMed, The
      Cochrane Library, Embase, and Google Scholar database was conducted to identify
      relevant articles in English, with the last report up to November 1, 2016.
      Heterogeneity test was performed, and publication bias was evaluated. Stata
      software 12.0 was used to perform the meta-analysis. Odds ratios (ORs) and 95%
      confidence intervals (CI) were used to describe the correlation by random-effects
      model. RESULTS: 18 studies were obtained after searching databases: 10 studies
      were about Caucasian, and 8 articles were about non-Caucasian. Meta-analysis
      revealed that the allele and phenotype frequencies of DQB1*05 were markedly
      higher in PV patients than in controls [P < 0.001, OR: 2.640, 95%CI: 1.570-4.441;
      P = 0.030, OR 3.688, 95%CI: 1.138-11.946]. In addition, DQB1*03 was significantly
      increased at the allele level [P < 0.001, OR: 2.080, 95%CI: 1.507-2.869], and
      DQB1*02 was significantly decreased in PV at the allele and phenotype levels [P =
      0.002, OR: 0.450, 95%CI: 0.289-0.702; P = 0.001, OR: 0.293, 95%CI: 0.146-0.587].
      When based on each subtype of HLA-DQB1, DQB1*05:03 and DQB1*03:02 may play
      susceptibility roles in PV, and DQB1*03:03, DQB1*05:01 and DQB1*06:01 are
      negatively associated with PV. CONCLUSION: In summary, our study suggests that
      alleles from the groups DQB1*05 and DQB1*03, concretely DQB1*05:03 and
      DQB1*03:02, respectively, may be the susceptibility factors for PV at allele and
      phenotype levels, whereas DQB1*05:01, DQB1*02, DQB1*06:01, and DQB1*03:03 are
      negatively associated with PV.

PMID- 29182410
TI  - The Effect of Periodization and Training Intensity Distribution on Middle- and
      Long-Distance Running Performance: A Systematic Review.
AB  - This review aimed to examine the current evidence for 3 primary training
      intensity distribution types: (1) pyramidal training, (2) polarized training, and
      (3) threshold training. Where possible, the training intensity zones relative to
      the goal race pace, rather than physiological or subjective variables, were
      calculated. Three electronic databases (PubMed, Scopus, and Web of Science) were
      searched in May 2017 for original research articles. After analysis of 493
      resultant original articles, studies were included if they met the following
      criteria: (1) Their participants were middle- or long-distance runners; (2) they
      analyzed training intensity distribution in the form of observational reports,
      case studies, or interventions; (3) they were published in peer-reviewed
      journals; and (4) they analyzed training programs with a duration of 4 wk or
      longer. Sixteen studies met the inclusion criteria, which included 6
      observational reports, 3 case studies, 6 interventions, and 1 review. According
      to the results of this analysis, pyramidal and polarized training are more
      effective than threshold training, although the latest is used by some of the
      best marathon runners in the world. Despite this apparent contradictory finding,
      this review presents evidence for the organization of training into zones based
      on a percentage of goal race pace, which allows for different periodization types
      to be compatible. This approach requires further development to assess whether
      specific percentages above and below race pace are key to inducing optimal
      changes.

PMID- 29182411
TI  - Interprofessional teamwork in comprehensive primary healthcare services: Findings
      from a mixed methods study.
AB  - This article draws on data from a 5-year project that examined the effectiveness
      of Comprehensive primary healthcare (CPHC) in local communities. A hallmark of
      CPHC services is interprofessional teamwork. Drawing from this study, our article
      presents factors that enabled, or hindered, healthcare teams working
      interprofessionally in Australian primary healthcare (PHC) services. The article
      reports on the experiences of teams working in six Australian PHC services (four
      managed by state governments, one non-government sexual health organisation, and
      one Aboriginal community-controlled health service) during a time of significant
      health sector restructure. Findings are drawn from two key methods: an online
      survey of practitioners and managers (n = 154), and interviews with managers and
      practitioners (n = 60) from the six study sites. The majority of survey
      respondents worked with other health professionals in their service to provide
      interprofessional care to clients. Processes included formal team meetings, case
      conferencing, referring clients to other health professionals if needed, informal
      communication with other health professionals about clients, and team-based
      delivery of care. A range of interrelated factors affected interprofessional work
      at the services, from contextual, organisational, processual, and relational
      domains. Funding cuts and policy changes that saw a reorientation and re
      medicalisation of South Australian services undermined interprofessional work,
      while a shared CPHC culture and commitment among some staff was helpful in
      resisting some of these effects. The co-location of services was a factor in PHC
      teams working interprofessionally and not only enabled some PHC teams to work
      more interprofessionally but also created barriers to interprofessional teamwork
      through disruption resulting from restructuring of services. Our study indicates
      the importance of decision makers taking into account the potential effects of
      policy and structural changes on interprofessional teamwork. Decision makers
      should strive to minimise unintended negative effects of changes on the
      functioning of interprofessional teams.

PMID- 29182412
TI  - The Effect of Water Loading on Acute Weight Loss Following Fluid Restriction in
      Combat Sports Athletes.
AB  - Novel methods of acute weight loss practiced by combat sport athletes include
      "water loading," the consumption of large fluid volumes for several days prior to
      restriction. We examined claims that this technique increases total body water
      losses, while also assessing the risk of hyponatremia. Male athletes were
      separated into control (n = 10) and water loading (n = 11) groups and fed a
      standardized energy-matched diet for 6 days. Days 1-3 fluid intake was 40 and 100
      ml/kg for control and water loading groups, respectively, with both groups
      consuming 15 ml/kg on Day 4 and following the same rehydration protocol on Days 5
      and 6. We tracked body mass (BM), urine sodium, urine specific gravity and
      volume, training-related sweat losses and blood concentrations of renal hormones,
      and urea and electrolytes throughout. Physical performance was assessed
      preintervention and postintervention. Following fluid restriction, there were
      substantial differences between groups in the ratio of fluid input/output (39%, p
      < .01, effect size = 1.2) and BM loss (0.6% BM, p = .02, effect size = 0.82).
      Changes in urine specific gravity, urea and electrolytes, and renal hormones
      occurred over time (p < .05), with an interaction of time and intervention on
      blood sodium, potassium, chloride, urea, creatinine, urine specific gravity, and
      vasopressin (p < .05). Measurements of urea and electrolyte remained within
      reference ranges, and no differences in physical performance were detected over
      time or between groups. Water loading appears to be a safe and effective method
      of acute BM loss under the conditions of this study. Vasopressin-regulated
      changes in aquaporin channels may potentially partially explain the mechanism of
      increased body water loss with water loading.

PMID- 29182413
TI  - Energetic Profile of the Basketball Exercise Simulation Test in Junior Elite
      Players.
AB  - PURPOSE: To analyze the energetic profile of the Basketball Exercise Simulation
      Test (BEST). METHODS: Ten male elite junior basketball players (age 15.5 [0.6] y,
      height 180 [9] cm, and body mass 66.1 [11.2] kg) performed a modified BEST (20
      circuits consisting of jumping, sprinting, jogging, shuffling, and short breaks)
      simulating professional basketball game play. Circuit time, sprint time, sprint
      decrement, oxygen uptake (VO2), heart rate, and blood lactate concentration (blc)
      were obtained. Metabolic energy and metabolic power above rest (Wtot and Ptot),
      as well as energy share in terms of aerobic (Waer), glycolytic (Wblc), and high
      energy phosphates (WPCr), were calculated from VO2 during exercise, net lactate
      production, and the fast component of postexercise VO2 kinetics, respectively.
      RESULTS: Waer, Wblc, and WPCr reflect 89% (2%), 5% (1%), and 6% (1%) of total
      energy needed, respectively. Assuming an aerobic replenishment of PCr energy
      stores during short breaks, the adjusted energy share yielded Waer 66% (4%), Wblc
      5% (1%), and WPCr 29% (1%). Waer and WPCr were negatively correlated (-0.72 and 
      0.59) with sprint time, which was not the case for Wblc. CONCLUSIONS: Consistent
      with general findings on energy system interaction during repeated high-intensity
      exercise bouts, the intermittent profile of the BEST relies primarily on aerobic
      energy combined with repetitive supplementation by anaerobic utilization of high
      energy phosphates.

PMID- 29182414
TI  - Cell-Free DNA as an Earlier Predictor of Exercise-Induced Performance Decrement
      Related to Muscle Damage.
AB  - PURPOSE: To evaluate whether cell-free DNA (cfDNA) levels increase immediately
      after an acute light and heavy resistance exercise (RE) bout and whether cfDNA
      levels are associated with functional muscle capacity up to 48 h after an
      exercise session. METHODS: Twenty healthy volunteers performed 3 sets of leg
      press RE with 80% of 1-repetition maximum (1RM) (RE80) or 40% of 1RM (RE40) with
      similar exercise volume. Blood lactate was measured after completion of the 3
      sets. Creatine kinase, cfDNA, and jump performance were evaluated before (pre)
      exercise, immediately postexercise (post-0h), and every 24 h until 48 h. RESULTS:
      Lactate concentration increased similarly in both groups (RE40 4.0 [1.3] mmol/L;
      RE80 4.8 [1.3] mmol/L). No changes were observed in squat-jump and
      countermovement-jump performance after RE40; however, both jumps remained reduced
      until 48 h in the RE80 group. Creatine kinase concentration increased post-24h
      only in the RE80 group (pre 128.8 [73.7] U/L to post-24h 313.8 [116.4] U/L).
      cfDNA concentration increased post-0h only in the RE80 group (pre 249.8 [82.3]
      ng/mL to post-0h 406.3 [67.2] ng/mL). There was a negative correlation between
      post-0h cfDNA concentration and post-24h squat jump (r = -.521; P = .01) and post
      0h cfDNA concentration and post-24h countermovement jump (r = -.539; P = .01).
      CONCLUSION: cfDNA increases in response to RE intensity even when not performed
      until exhaustion. cfDNA measured immediately after RE is a promising biomarker
      for muscle-performance decrement up to 48 h after a RE bout.

PMID- 29182415
TI  - Validity and Reliability of the Cycleops Hammer Cycle Ergometer.
AB  - PURPOSE: To validate the new drive indoor trainer Hammer designed by Cycleops(r).
      METHODS: A total of 11 cyclists performed 44 randomized and counterbalanced
      graded exercise tests (100-500 W) at 70-, 85-, and 100-rpm cadences in seated and
      standing positions on 3 different Hammer units, while a scientific SRM system
      continuously recorded cadence and power output data. RESULTS: No significant
      differences were detected between the 3 Hammer devices and the SRM for any
      workload, cadence, or pedaling condition (P value between 1.00 and .350), except
      for some minor differences (P = .03 and .04) found in the Hammer 1 at low
      workloads and for Hammer 2 and 3 at high workloads, all in seated position.
      Strong intraclass correlation coefficients were found between the power output
      values recorded by the Hammers and the SRM (>=.996; P = .001), independently from
      the cadence condition and seated position. Bland-Altman analysis revealed low
      bias (-5.5 to 3.8) and low SD of bias (2.5-5.3) for all testing conditions,
      except marginal values found for the Hammer 1 at high cadences and seated
      position (9.6 [6.6]). High absolute reliability values were detected for the 3
      Hammers (150-500 W; coefficient of variation <1.2%; SEM <2.1). CONCLUSIONS: This
      new Cycleops trainer is a valid and reliable device to drive and measure power
      output in cyclists, providing an alternative to larger and more expensive
      laboratory ergometers and allowing cyclists to use their own bicycles.

PMID- 29182416
TI  - Ex vivo Stimulation of Lymphocytes with IL-10 Mimics Sepsis-Induced Intrinsic T
      Cell Alterations.
AB  - Profound T-cell alterations are observed in septic patients in association with
      increased risk of secondary infection and mortality. The pathophysiological
      mechanisms leading to such dysfunctions are not completely understood and direct
      and indirect mechanisms have been described. In this study we evaluated whether
      ex vivo stimulation of lymphocytes with IL-10, an immunosuppressive cytokine
      released at the systemic level during sepsis, could mimic sepsis-induced
      intrinsic T-cell alterations. We showed that recombinant human IL-10 priming of T
      cells altered their proliferative response to anti-CD2/CD3/CD28 antibody-coated
      beads and PHA stimulations, in a dose-dependent manner independently of accessory
      cells. This priming also significantly decreased T-cell secretion of IL-2 and
      IFNgamma following stimulation. Furthermore, we demonstrated that IL-10 reduction
      of T-cell functionality was associated with increased FOXP3 expression in
      CD4+CD25+CD127- regulatory T cells as observed in sepsis. Finally, we found that
      blocking the increased IL-10 concentration in plasma from septic shock patients
      increased the proliferative response of responding T cells from healthy controls.
      We describe here an ex vivo model recapitulating features of sepsis-induced
      intrinsic T-cell alterations. This should help, in further studies, to decipher
      the pathophysiological mechanisms of T-cell alterations induced after septic
      shock.

PMID- 29182417
TI  - Seasonal Training Load and Wellness Monitoring in a Professional Soccer
      Goalkeeper.
AB  - The purpose of this investigation was to (1) quantify the training load practices
      of a professional soccer goalkeeper and (2) investigate the relationship between
      the training load observed and the subsequent self-reported wellness response.
      One male goalkeeper playing for a team in the top league of the Netherlands
      participated in this case study. Training load data were collected across a full
      season using a global positioning system device and session-RPE (rating of
      perceived exertion). Data were assessed in relation to the number of days to a
      match (MD- and MD+). In addition, self-reported wellness response was assessed
      using a questionnaire. Duration, total distance, average speed, PlayerLoadTM, and
      load (derived from session-RPE) were highest on MD. The lowest values for
      duration, total distance, and PlayerLoadTM were observed on MD-1 and MD+1. Total
      wellness scores were highest on MD and MD-3 and were lowest on MD+1 and MD-4.
      Small to moderate correlations between training load measures (duration, total
      distance covered, high deceleration efforts, and load) and the self-reported
      wellness response scores were found. This exploratory case study provides novel
      data about the physical load undertaken by a goalkeeper during 1 competitive
      season. The data suggest that there are small to moderate relationships between
      training load indicators and self-reported wellness response. This weak relation
      indicates that the association is not meaningful. This may be due to the lack of
      position-specific training load parameters that practitioners can currently
      measure in the applied context.

PMID- 29182418
TI  - Associations Between Bicycling and Reduced Fall-Related Physical Performance in
      Older Adults.
AB  - Falls among older adults remain a significant public health issue. Bicycling
      positively influences falls risk factors including reduced balance, muscle
      weakness, and low self-perceived confidence in maintaining balance. However, this
      association has not been systematically examined. We recruited 107 community
      dwelling participants aged 65 years and older in the Netherlands to determine the
      relationship between bicycling and falls risk factors. Participants completed
      three questionnaires on cycling behavior and balance confidence, and also
      undertook five falls-related physical performance tasks encompassing tests of
      balance, strength, gait, and endurance. On average, current bicyclists showed
      significantly better scores in all physical tasks and confidence compared with
      nonriders ranging from a 10% difference in 6-m walk time to a 141% difference in
      single-leg balance time (all ps = .01). Type of bike used and duration of
      bicycling displayed varied associations (.01 < ps < .79). Our findings suggest
      that bicycle riding warrants further prospective investigation for fall
      prevention and active aging.

PMID- 29182419
TI  - Psychometric Properties of the Modified Social Environment Questionnaire in
      Chinese Older Adults.
AB  - This study evaluated the psychometric properties of a Chinese version of the 24
      item Social Environment Questionnaire (SEQ-C). Confirmatory factor analysis was
      used to examine the factor validity and measurement invariance (Purpose 1) of the
      SEQ-C in 453 older adults in Hong Kong. Convergent validity (Purpose 2) and test
      retest reliability (Purpose 3) were also measured. The results of the
      confirmatory factor analysis and measurement invariance supported the four-factor
      structure (representing companionship, encouragement, neighborhood social
      cohesion, and role models) of the SEQ-C, in a 15-item model that closely fitted
      the data. The SEQ-C was also found to have acceptable to satisfactory internal
      consistency, test-retest reliability, composite reliability, and moderate
      convergent validity in correlating perceived social support. This study showed
      that the SEQ-C is a suitable means of measuring the social environments of older
      adults in Hong Kong.

PMID- 29182420
TI  - Timeliness of vaccination in infants followed by primary-care pediatricians in
      France.
AB  - Vaccination status is more often evaluated by up-to-date vaccination coverage
      rather than timeliness of immunization. Delaying vaccination may be dangerous
      during infancy. The aim of this study was to identify the importance of
      potentially dangerous vaccination delay (previously defined) and determinants of
      these delays. We conducted a national, prospective, vaccination survey in June
      2014, with primary care pediatricians. Children, 2 to 24 months of age, were
      included. Data about vaccination were extracted from their health books.
      Additional data were collected through a standardized questionnaire. Vaccine
      coverage rate and timeliness were calculated. Variables associated with a
      potentially dangerous vaccination delay as previously defined were determined by
      a multivariable analysis. Among the 443 included children (mean age 10.8 months,
      49% males), 13% to 58% of vaccine doses according to vaccine type were done with
      a potentially dangerous delay. Globally, 47% of children had at least one
      potentially dangerous immunization delay. We identified two risk factors of
      potentially dangerous delayed immunization globally: an increasing age of the
      child (adjusted odds ratio: 1.2, 95% confidence interval [CI]: 1.1-1.3, p < 10
      3), and a working mother (adjusted OR: 2.4, 95% CI: 1.2-4.7, p = 0.01). Despite a
      good vaccine coverage rate, a large number of children had a potentially
      dangerous vaccination delay. A high level of vigilance regarding these
      immunization delays, and particularly to the patients sharing the risk factors of
      immunization delay identified here, can increase quality and effectiveness of the
      vaccine protection.

PMID- 29182422
TI  - Salivary Biomarkers and Training Load During Training and Competition in
      Paralympic Swimmers.
AB  - CONTEXT: Stress responses in athletes can be attributed to training and
      competition, where increased physiological and psychological stress may
      negatively affect performance and recovery. PURPOSE: To examine the relationship
      between training load (TL) and salivary biomarkers immunoglobulin A (IgA), alpha
      amylase (AA), and cortisol across a 16-wk preparation phase and 10-d competition
      phase in Paralympic swimmers. METHODS: Four Paralympic swimmers provided biweekly
      saliva samples during 3 training phases-(1) normal training, (2) intensified
      training, and (3) taper-as well as daily saliva samples in the 10-d Paralympic
      competition (2016 Paralympic Games). TL was measured using session rating of
      perceived exertion. RESULTS: Multilevel analysis identified a significant
      increase in salivary immunoglobulin A (sIgA: 94.98 [27.69] MUg.mL-1), salivary
      alpha-amylase (sAA: 45.78 [19.07] MUg.mL-1), and salivary cortisol (7.92 [2.17]
      nM) during intensified training concurrent with a 38.3% increase in TL. During
      the taper phase, a 49.5% decrease in TL from the intensified training phase
      resulted in a decrease in sIgA, sAA, and salivary cortisol; however, all 3
      remained higher than baseline levels. A further significant increase was observed
      during competition in sIgA (168.69 [24.19] MUg.mL-1), sAA (35.86 [16.67] MUg.mL
      1), and salivary cortisol (10.49 [1.89] nM) despite a continued decrease (77.8%)
      in TL from the taper phase. CONCLUSIONS: Results demonstrate that performance in
      major competition such as Paralympic games, despite a noticeable reduction in TL,
      induces a stress response in athletes. Because of the elevated stress response
      observed, modifications to individual postrace recovery protocols may be required
      to enable athletes to maximize performance across all 10 d of competition.

PMID- 29182421
TI  - Feeding strategy shapes gut metagenomic enrichment and functional specialization
      in captive lemurs.
AB  - Many studies have demonstrated the effects of host diet on gut microbial
      membership, metagenomics, and fermentation individually; but few have attempted
      to interpret the relationship among these biological phenomena with respect to
      host features (e.g. gut morphology). We quantitatively compare the fecal
      microbial communities, metabolic pathways, and fermentation products associated
      with the nutritional intake of frugivorous (fruit-eating) and folivorous (leaf
      eating) lemurs. Our results provide a uniquely multidimensional and comparative
      perspective on the adaptive dynamics between host and microbiome. Shotgun
      metagenomic sequencing revealed significant differential taxonomic and metabolic
      pathway enrichment, tailored to digest and detoxify different diets. Frugivorous
      metagenomes feature pathways to degrade simple carbohydrates and host-derived
      glycosaminoglycans, while folivorous metagenomes are equipped to break down
      phytic acid and other phytochemical compounds in an anaerobic environment. We
      used nuclear magnetic resonance based metabolic profiling of fecal samples to
      link metabolic pathways to fermentation products, confirming that the dissimilar
      substrates provided in each diet select for specific microbial functions. Fecal
      samples from frugivorous lemurs contained significantly different profiles of
      short chain fatty acids, alcohol fermentation products, amino acids, glucose, and
      glycerol compared to folivorous lemurs. We present the relationships between
      these datasets as an integrated visual framework, which we refer to as microbial
      geometry. We use microbial geometry to compare empirical gut microbial profiles
      across different feeding strategies, and suggest additional utility as a tool for
      hypothesis-generation.

PMID- 29182423
TI  - The Digest.

PMID- 29182424
TI  - Bioactivation of cyclopropyl rings by P450: an observation encountered during the
      optimisation of a series of hepatitis C virus NS5B inhibitors.
AB  - 1. Due to its unique C-C and C-H bonding properties, conformational preferences
      and relative hydrophilicity, the cyclopropyl ring has been used as a synthetic
      building block in drug discovery to modulate potency and drug-like properties.
      During an effort to discover inhibitors of the hepatitis C virus non-structural
      protein 5B with improved potency and genotype-coverage profiles, the use of a
      pyrimidinylcyclopropylbenzamide moiety linked to a C6-substituted benzofuran or
      azabenzofuran core scaffold was explored in an effort to balance antiviral
      potency and metabolic stability. 2. In vitro metabolism studies of two compounds
      from this C6-substituted series revealed an NADPH-dependent bioactivation pathway
      leading to the formation of multiple glutathione (GSH) conjugates. Analysis of
      these conjugates by LC-MS and NMR demonstrated that the cyclopropyl group was the
      site of bioactivation. Based on the putative structures and molecular weights of
      the cyclopropyl-GSH conjugates, a multi-step mechanism was proposed to explain
      the formation of these metabolites by P450. This mechanism involves hydrogen atom
      abstraction to form a cyclopropyl radical, followed by a ring opening
      rearrangement and reaction with GSH. 3. These findings provided important
      information to the medicinal chemistry team which responded by replacing the
      cyclopropyl ring with a gem-dimethyl group. Subsequent compounds bearing this
      feature were shown to avert the bioactivation pathways in question.

PMID- 29182425
TI  - Endothelial alterations in a canine model of immune thrombocytopenia.
AB  - Bleeding heterogeneity amongst patients with immune thrombocytopenia (ITP) is
      poorly understood. Platelets play a role in maintaining endothelial integrity,
      and variable thrombocytopenia-induced endothelial changes may influence bleeding
      severity. Platelet-derived endothelial stabilizers and markers of endothelial
      integrity in ITP are largely underexplored. We hypothesized that, in a canine ITP
      model, thrombocytopenia would lead to alterations in the endothelial
      ultrastructure and that the Von Willebrand factor (vWF) would serve as a marker
      of endothelial injury associated with thrombocytopenia. Thrombocytopenia was
      induced in healthy dogs with an antiplatelet antibody infusion; control dogs
      received an isotype control antibody. Cutaneous biopsies were obtained prior to
      thrombocytopenia induction, at platelet nadir, 24 hours after nadir, and on
      platelet recovery. Cutaneous capillaries were assessed by electron microscopy for
      vessel thickness, the number of pinocytotic vesicles, the number of large
      vacuoles, and the number of gaps between cells. Pinocytotic vesicles are thought
      to represent an endothelial membrane reserve that can be used for repair of
      damaged endothelial cells. Plasma samples were assessed for vWF. ITP dogs had
      significantly decreased pinocytotic vesicle numbers compared to control dogs (P =
      0.0357) and the increase in plasma vWF from baseline to 24 hours correlated
      directly with the endothelial large vacuole score (R = 0.99103; P < 0.0001). This
      direct correlation between plasma vWF and the number of large vacuoles,
      representing the vesiculo-vacuolar organelle (VVO), a permeability structure,
      suggests that circulating vWF could serve as a biomarker for endothelial
      alterations and potentially a predictor of thrombocytopenic bleeding. Overall,
      our results indicate that endothelial damage occurs in the canine ITP model and
      variability in the degree of endothelial damage may account for differences in
      the bleeding phenotype among patients with ITP.

PMID- 29182426
TI  - Effects of Single Set Resistance Training With Different Frequencies on a
      Cellular Health Indicator in Older Women.
AB  - The main purpose of this study was to compare the effects of resistance training
      (RT) performed two versus three times per week on phase angle (a cellular health
      indicator) in older women. A total of 39 women (69.1 +/- 5.5 years) were randomly
      assigned to perform a RT program two (G2X) or three (G3X) days per week for 12
      weeks. The RT was a whole-body program (eight exercises, one set, 10-15
      repetitions). Phase angle, resistance, reactance, and total body water were
      assessed by bioimpedance spectroscopy. Intracellular water, reactance, and phase
      angle increased significantly in G2X (2.1%, 3.0%, and 5.6%, respectively) and G3X
      (5.0%, 6.9%, and 10.3%, respectively) from pretraining to posttraining, with no
      significant difference between groups. Bioimpedance resistance decreased
      similarly in both groups (G2X = -1.7% vs. G3X = -3.2%). We conclude that a single
      set RT program with a frequency of 2 days per week may be sufficient to promote
      an improvement in cellular health in older women.

PMID- 29182428
TI  - O-Acetylation is essential for functional antibody generation against
      Staphylococcus aureus capsular polysaccharide.
AB  - Staphylococcus aureus produces an antiphagocytic polysaccharide capsule to evade
      neutrophil-mediated killing. Many vaccines against encapsulated bacterial
      pathogens require generation of functional anti-capsular antibodies to mediate
      protection against infection and disease. Here it is shown that the generation of
      such antibody responses to S. aureus in vivo and in vitro requires the presence
      of O-acetyl modifications on the capsular polysaccharides. O-acetylation of S.
      aureus capsular polysaccharide therefore should be monitored carefully during
      vaccine development and production. This finding may provide additional insight
      into the previous failure of a S. aureus capsular polysaccharide conjugate
      vaccine.

PMID- 29182429
TI  - The relationship between methylenetetrahydrofolate reductase C677T polymorphism
      and diabetic retinopathy: A meta-analysis in multiethnic groups.
AB  - BACKGROUND: Many studies have analyzed the association between
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and diabetic
      retinopathy (DR), however, the results remained inconclusive. We therefore aim to
      address this association by performing a meta-analysis in multiethnic groups.
      METHODS: Related studies were identified from PubMed and Chinese databases up to
      October 2016. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were
      used to assess the strength of the associations. RESULTS: A total of 20 studies
      including 1860 DR cases and 3646 controls were involved in this meta-analysis. In
      the overall population, we found that MTHFR C677T polymorphism was significantly
      associated with an increased risk of DR for each genetic model. In this meta
      analysis stratified by ethnicity, significantly increased risk of DR with the
      MTHFR C677T variants was found in the Chinese, Japanese, and Turks populations.
      CONCLUSIONS: Our study suggested that the MTHFR C677T polymorphism may contribute
      to DR development in multiethnic groups. Studies with larger sample sizes and
      wider spectrum of populations are warranted to verify this finding.

PMID- 29182430
TI  - On evaluation of consistency in multi-regional clinical trials.
AB  - In recent years, multi-regional clinical trials (MRCT) that conduct clinical
      trials simultaneously in Asian Pacific region, Europe, and the United States have
      become very popular for global pharmaceutical development. The main purpose of
      multi-regional clinical trials is to shorten the time for pharmaceutical
      development and regulatory submission, and approval around the world. In
      practice, however, clinical results observed from some regions (sub-population)
      may not be consistent with the results from other regions and/or all regions
      combined (entire population). The inconsistency observed may be due to ethnic
      differences in different regions, differences in medical practice, time points of
      assessment, or by random chance due to small sample size for the region. Some
      regional regulatory agencies require consistency evaluation between local country
      results and overall results. However, the challenge is there is no detailed
      guidance on the definition of 'consistency' and methodology to evaluate it.
      Therefore, the questions are: how to evaluate consistency and what statistical
      methods are appropriate to be used for consistency evaluation? In this article,
      several statistical tests for consistency (similarity) between clinical results
      observed from a specific sub-population and the entire population are proposed.
      These methods are compared through extensive simulation. As most published
      articles discussed consistency evaluation for superiority situations, we have
      discussed consistency evaluation for non-inferiority situation in this article
      through a simulated example concerning consistency in some countries.
      Recommendations of the statistical methods to be used for consistency evaluation
      are given. Other aspects that should be considered for consistency evaluation are
      also provided.

PMID- 29182431
TI  - Impact-Induced Muscle Damage and Contact Sports: Etiology, Effects on
      Neuromuscular Function and Recovery, and the Modulating Effects of Adaptation and
      Recovery Strategies.
AB  - Athletes involved in contact sports are habitually exposed to skeletal-muscle
      damage in their training and performance environments. This often leads to
      exercise-induced muscle damage (EIMD) resulting from repeated eccentric and/or
      high-intensity exercise and to impact-induced muscle damage (IIMD) resulting from
      collisions with opponents and the playing surface. While EIMD has been an area of
      extensive investigation, IIMD has received comparatively little research, with
      the magnitude and time frame of alterations following IIMD not presently well
      understood. It is currently thought that EIMD results from an overload of
      mechanical stress that causes ultrastructural damage to the cellular membrane
      constituents. Damage leads to compromised ability to produce force, which
      manifests immediately and persists for up to 14 d following exercise exposure.
      IIMD has been implicated in attenuated neuromuscular performance and recovery and
      in inflammatory processes, although the underlying course over time remains
      unclear. Exposure to EIMD leads to an adaptation to subsequent exposures, a
      phenomenon known as the repeated-bout effect. An analogous adaptation has been
      suggested to occur following IIMD; however, to date, this contention remains
      equivocal. While a considerable body of research has explored the efficacy of
      recovery strategies following EIMD, strategies promoting recovery from IIMD are
      limited to investigations using animal contusion models. Strategies such as
      cryotherapy and antioxidant supplementation that focus on attenuating the
      secondary inflammatory response may provide additional benefit in IIMD and are
      explored herein. Further research is required to first establish a model of
      generating IIMD and then explore broader areas around IIMD in athletic
      populations.

PMID- 29182432
TI  - Temporal Consistency and Movement Effort of Repetitive Reaching During
      Continuation in Children and Adults.
AB  - The ability to match one's movements to an external beat and maintain that rhythm
      in the absence of the beat suggests sophisticated, well-developed neural control.
      Children (aged 5-10 years) were compared with adults (aged 18-30 years) during a
      repetitive reaching task to determine development of this control. Children as
      young as 5 years exhibited this control. The mean rate of reaching did not differ
      between groups nor did it differ during the two phases, suggesting an overall
      ability to internalize and continuously repeat a given pace. Children aged 5-8
      years were significantly more variable than children aged 9-10 years and adults,
      likely attributable to variability in central control processes. We found a
      possible transition period of temporal control. Children aged 9-10 years begin to
      exhibit more adult-like levels of variability with respect to temporal
      consistency and movement effort.

PMID- 29182433
TI  - An Experimental Method to Estimate Upper Limbs Inertial Parameters During
      Handcycling.
AB  - This study proposes an experimental method to estimate personalized inertial
      parameters of upper limbs during handcycling by using a planar dynamic model. The
      handle forces are expressed as a product of a matrix describing the kinematics
      terms and a vector of inertial parameters of arm and forearm. The parameters are
      estimated by measuring the handle forces during a suitable "passive test" and
      inverting the mentioned matrix. The data were acquired while an operator actuated
      the handle and the subject's muscles were relaxed. To validate the estimation
      procedure, it was applied to a custom-made artificial arm mechanism, and the
      results were compared with its known parameters. The method was then used to
      estimate the inertial parameters of 6 human subjects. The estimated parameters
      were used to compute the exchanged forces and compared with the measured ones
      obtaining an average error of 14% both for Fx and Fy. These errors are
      significantly smaller than those obtained using dynamic parameters extracted from
      the literature to compute the forces, which were 50% for Fx and 19% for Fy. An
      individual evaluation of inertial parameters better describes interaction forces
      during handcycling, especially for subjects whose body structures are different
      from the average population.

PMID- 29182434
TI  - Reactive Strength Index: A Poor Indicator of Reactive Strength?
AB  - PURPOSE: To assess the relationships between reactive strength measures and
      associated kinematic and kinetic performance variables achieved during drop
      jumps. A secondary aim was to highlight issues with the use of reactive strength
      measures as performance indicators. METHODS: Twenty-eight national- and
      international-level sprinters, 14 men and 14 women, participated in this cross
      sectional analysis. Athletes performed drop jumps from a 0.3-m box onto a force
      platform with dependent variables contact time (CT), landing time, push-off time,
      flight time, jump height (JH), reactive strength index (RSI, calculated as
      JH/CT), reactive strength ratio (RSR, calculated as flight time/CT), and vertical
      leg-spring stiffness recorded. RESULTS: A Pearson correlation test found very
      high to near-perfect relationships between RSI and RSR (r = .91-.97), with mixed
      relationships between RSI, RSR, and the key performance variables (men: r = -.86
      to -.71 between RSI/RSR and CT, r = .80-.92 between RSI/RSR and JH; women: r = 
      .85 to -.56 between RSR and CT, r = .71 between RSI and JH). CONCLUSIONS: The
      method of assessing reactive strength (RSI vs RSR) may be influenced by the
      performance strategies adopted, that is, whether athletes achieve their best
      reactive strength scores via low CTs, high JHs, or a combination. Coaches are
      advised to limit the variability in performance strategies by implementing upper
      and/or lower CT thresholds to accurately compare performances between
      individuals.

PMID- 29182435
TI  - Racial and Ethnic Differences in Mental Health among Asian Americans and Non
      Hispanic Whites: Based on California Health Interview Survey.
AB  - While Asians are becoming the largest ethnic group in the United States, studies
      have focused on Asians as a single population. The purpose of this study was to
      explore the racial and ethnic mental health differences between non-Hispanic
      Whites and Asians, with an emphasis on understudied subgroups, from the
      California Health Interview Survey 2011/2012. In this dataset Asians had
      significantly lower adjusted odds ratios for both mental distress and serious
      mental illness. However, when Asians were divided into subgroups and compared to
      Whites, Vietnamese and Japanese subgroups were significantly lower than Whites
      for mental distress while Koreans were significantly higher. Vietnamese and
      Chinese were found to have significantly less serious mental illness than Whites
      in the subgroup analyses. Our results underscore the importance of recognizing
      that Asian subgroups should not be overlooked, and all Asians should not
      automatically be treated as a homogenous group.

PMID- 29182436
TI  - Vertical and Horizontal Jump Capacity in International Cerebral Palsy Football
      Players.
AB  - PURPOSE: To evaluate the reliability and validity of vertical and horizontal jump
      tests in football players with cerebral palsy (FPCP) and to analyze the jump
      performance differences between current International Federation for Cerebral
      Palsy Football functional classes (ie, FT5-FT8). METHODS: A total of 132
      international parafootballers (25.8 [6.7] y; 70.0 [9.1] kg; 175.7 [7.3] cm; 22.8
      [2.8] kg.m-2; and 10.7 [7.5] y training experience) participated in the study.
      The participants were classified according to the International Federation for
      Cerebral Palsy Football classification rules, and a group of 39 players without
      cerebral palsy was included in the study as a control group. Football players'
      vertical and horizontal jump performance was assessed. RESULTS: All the tests
      showed good to excellent relative intrasession reliability scores, both in FPCP
      and in the control group (intraclass correlation = .78-.97, SEM < 10.5%).
      Significant between-groups differences (P < .001) were obtained in the
      countermovement jump, standing broad jump, 4 bounds for distance, and triple hop
      for distance dominant leg and nondominant leg. The control group performed
      higher/farther jumps with regard to all the FPCP classes, obtaining significant
      differences and moderate to large effect sizes (ESs) (.85 < ES < 5.54, P < .01).
      Players in FT8 class (less severe impairments) had significantly higher scores in
      all the jump tests than players in the lower classes (ES = moderate to large, P <
      .01). CONCLUSIONS: The vertical and horizontal jump tests performed in this study
      could be applied to the classification procedures and protocols for FPCP.

PMID- 29182437
TI  - Immunotherapy for pet allergies.
AB  - Allergic diseases compose a serious challenge for modern societies. Their
      individual, medical and economical burden is large. As humans spend most of their
      time indoors, exposure to indoor allergens is a significant contributor to the
      development of allergic sensitization and respiratory allergies, such as allergic
      rhinoconjunctivitis and asthma. One important source of indoor allergens are
      pets, in particular cats and dogs. Allergens from these and other mammals spread
      effectively and they are encountered widely in public places. If patient
      education, allergen avoidance and pharmacotherapy do not suffice for controlling
      the symptoms of pet allergy, allergen immunotherapy can be a treatment option.
      Current information on allergen immunotherapy in pet allergy suggests that it can
      be effective in reducing allergic symptoms. However, the low number of high
      quality randomized controlled trials of allergen immunotherapy in pet allergy
      warrants for further investigations.

PMID- 29182438
TI  - High numbers of myeloid derived suppressor cells in peripheral blood and ascitic
      fluid of cirrhotic and HCC patients.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer
      related death worldwide. It has evolved different immune escape mechanisms, which
      might include emergence of lymphoid and myeloid regulatory cells. Aim of this
      work: To determine the numbers of Myeloid-derived suppressor cells (MDSCs) in
      peripheral blood and ascitic fluid in cirrhosis and HCC and their relation to IFN
      gamma and alpha-fetoprotein (alpha-FP). PATIENTS AND METHODS: Sixty individuals
      were enrolled in this study; forty cirrhotic patients with ascites; twenty
      without HCC (Group I), and twenty with HCC (group II) as well as twenty healthy
      individuals as a control group (group III). The phenotype and numbers of MDSCs
      were analyzed in peripheral blood of all the individuals and ascitic fluid of the
      patients using flow cytometry. Intracellular IFN-gamma and serum alfa-fetoprotein
      were measured. RESULTS: Significant increases in the relative and the mean number
      of peripheral blood MDSCs were found in the cirrhosis and HCC groups than in the
      control group, with the HCC group showing the highest number. MDSC count was
      negatively correlated with IFN-gamma levels, while alpha-FP was positively
      correlated with MDSC% in the HCC group. MDSC count was low in ascitic fluid of
      both HCC and cirrhosis groups with no significant difference between the 2
      groups. CONCLUSION: A high frequency of MDSCs was detected in the peripheral
      blood of cirrhotic and HCC patients, indicating presence of immunosuppressive
      arms. These cells could be targeted to develop a new effective immunotherapy or
      an adjuvant to current therapies.

PMID- 29182440
TI  - The Action Level.

PMID- 29182439
TI  - Chondrocyte-based intraoperative processing strategies for the biological
      augmentation of a polyurethane meniscus replacement.
AB  - : Purpose/aim of study: Menisectomies account for over 1.5 million surgical
      interventions in Europe annually, and there is a growing interest in regenerative
      strategies to improve outcomes in meniscal replacement. The overall objective of
      this study was to evaluate the role of intraoperatively applied fresh chondrocyte
      (FC) isolates compared to minced cartilage (MC) fragments, used without cell
      isolation, to improve bioactivity and tissue integration when combined with a
      polyurethane replacement. MATERIALS AND METHODS: First, to optimize the
      intraoperative cell isolation protocol, caprine articular cartilage biopsies were
      digested with 750 U/ml or 3000 U/ml collagenase type II (ratio of 10 ml per g of
      tissue) for 30 min, 1 h or 12 h with constant agitation and compared to culture
      expanded chondrocytes in terms of matrix deposition when cultured on polyurethane
      scaffolds. Finally, FCs and MC-augmented polyurethane scaffolds were evaluated in
      a caprine meniscal explant model to assess the potential enhancements on tissue
      integration strength. RESULTS: Adequate numbers of FCs were harvested using a 30
      min chondrocyte isolation protocol and were found to demonstrate improved matrix
      deposition compared to standard culture-expanded cells in vitro. Upon evaluation
      in a meniscus explant defect model, both FCs and MC showed improved matrix
      deposition at the tissue-scaffold interface and enhanced push-out strength,
      fourfold and 2.5-fold, respectively, compared with the acellular implant.
      CONCLUSIONS: Herein, we have demonstrated a novel approach that could be applied
      intraoperatively, using FCs or MC for improved tissue integration with a
      polyurethane meniscal replacement.

PMID- 29182444
TI  - Performance validity testing in neuropsychology: a clinical guide, critical
      review, and update on a rapidly evolving literature.
AB  - OBJECTIVE: Over the past two decades, there has been much research on measures of
      response bias and myriad measures have been validated in a variety of clinical
      and research samples. This critical review aims to guide clinicians through the
      use of performance validity tests (PVTs) from test selection and administration
      through test interpretation and feedback. METHOD/RESULTS: Recommended cutoffs and
      relevant test operating characteristics are presented. Other important issues to
      consider during test selection, administration, interpretation, and feedback are
      discussed including order effects, coaching, impact on test data, and methods to
      combine measures and improve predictive power. When interpreting performance
      validity measures, neuropsychologists must use particular caution in cases of
      dementia, low intelligence, English as a second language/minority cultures, or
      low education. CONCLUSIONS: PVTs provide valuable information regarding response
      bias and, under the right circumstances, can provide excellent evidence of
      response bias. Only after consideration of the entire clinical picture, including
      validity test performance, can concrete determinations regarding the validity of
      test data be made.

PMID- 29182441
TI  - Elimination of tumor by CD47/PD-L1 dual-targeting fusion protein that engages
      innate and adaptive immune responses.
AB  - The host immune system generally serves as a barrier against tumor formation.
      Programmed death-ligand 1 (PD-L1) is a critical "don't find me" signal to the
      adaptive immune system, whereas CD47 transmits an anti-phagocytic signal, known
      as the "don't eat me" signal, to the innate immune system. These and similar
      immune checkpoints are often overexpressed on human tumors. Thus, dual targeting
      both innate and adaptive immune checkpoints would likely maximize anti-tumor
      therapeutic effect and elicit more durable responses. Herein, based on the
      variable region of atezolizumab and consensus variant 1 (CV1) monomer, we
      constructed a dual-targeting fusion protein targeting both CD47 and PD-L1 using
      "Knobs-into-holes" technology, denoted as IAB. It was effective in inducing
      phagocytosis of tumor cells, stimulating T-cell activation and mediating antibody
      dependent cell-mediated cytotoxicity in vitro. No obvious sign of hematological
      toxicity was observed in mice administered IAB at a dose of 100 mg/kg, and IAB
      exhibited potent antitumor activity in an immune-competent mouse model of MC38.
      Additionally, the anti-tumor effect of IAB was impaired by anti-CD8 antibody or
      clodronate liposomes, which implied that both CD8+ T cells and macrophages were
      required for the anti-tumor efficacy of IAB and IAB plays an essential role in
      the engagement of innate and adaptive immune responses. Collectively, these
      results demonstrate the capacity of an elicited endogenous immune response
      against tumors and elucidate essential characteristics of synergistic innate and
      adaptive immune response, and indicate dual blockade of CD47 and PD-L1 by IAB may
      be a synergistic therapy that activates both innate and adaptive immune response
      against tumors.

PMID- 29182443
TI  - Exploring the Factor Structure of Financial Capacity in Cognitively Normal and
      Impaired Older Adults.
AB  - OBJECTIVES: To investigate the factor structure of financial capacity using a
      direct-performance measure of financial skills (The Financial Capacity Instrument
      [FCI]) as a proxy for the financial capacity construct. METHODS: The study sample
      was composed of 440 older adults who represented the cognitive spectrum from
      normal cognitive aging to mild cognitive impairment (MCI) to mild dementia: 179
      healthy older adults, 149 participants with MCI, and 112 participants with mild
      Alzheimer's dementia (AD). RESULTS: Both Velicer's Minimum Average Partial test
      and Horn's parallel analysis supported a four-factor solution which accounted for
      46% of variance. The four extracted factors were interpreted as: (1) Basic
      Monetary Knowledge and Calculation Skills, (2) Financial Judgment, (3) Financial
      Conceptual Knowledge, and (4) Financial Procedural Knowledge. CONCLUSIONS: The
      study findings represent an important first step in empirically articulating the
      financial capacity construct in aging. The four identified factors can guide both
      clinical practice and future instrument utilization and development. CLINICAL
      IMPLICATIONS: Cognitively impaired older adults with MCI and mild AD dementia are
      likely to show financial changes in one or more of the four identified financial
      factors. Clinicians working with older adults should routinely examine for
      potential changes in these four areas of financial function.

PMID- 29182445
TI  - Attractiveness as a Function of Skin Tone and Facial Features: Evidence from
      Categorization Studies.
AB  - Participants rated the attractiveness and racial typicality of male faces varying
      in their facial features from Afrocentric to Eurocentric and in skin tone from
      dark to light in two experiments. Experiment 1 provided evidence that facial
      features and skin tone have an interactive effect on perceptions of
      attractiveness and mixed-race faces are perceived as more attractive than single
      race faces. Experiment 2 further confirmed that faces with medium levels of skin
      tone and facial features are perceived as more attractive than faces with extreme
      levels of these factors. Black phenotypes (combinations of dark skin tone and
      Afrocentric facial features) were rated as more attractive than White phenotypes
      (combinations of light skin tone and Eurocentric facial features); ambiguous
      faces (combinations of Afrocentric and Eurocentric physiognomy) with medium
      levels of skin tone were rated as the most attractive in Experiment 2.
      Perceptions of attractiveness were relatively independent of racial
      categorization in both experiments.

PMID- 29182446
TI  - Lesbians and tech: Analyzing digital media technologies and lesbian experience.
AB  - The rise of the popular Internet has coincided with the increasing acceptance,
      even assimilation, of lesbians into mainstream society. The visible presence of
      lesbians in the tech industry and in digitally mediated spaces raises a set of
      questions about the relationship between queer identities and Internet
      technologies. This introduction to a special issue of Journal of Lesbian Studies
      explores some of these questions and provides an overview of the articles that
      follow.

PMID- 29182447
TI  - Nursing Home Residents: Age-Friendly Communities.

PMID- 29182448
TI  - Cerebrospinal Fluid Cytokine Expression Profile in Multiple Sclerosis and Chronic
      Inflammatory Demyelinating Polyneuropathy.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) analysis in patients with particular
      neurologic disorders is a powerful tool to evaluate specific central nervous
      system inflammatory markers for diagnostic needs, because CSF represents the
      specific immune micro-environment to the central nervous system. METHODS: CSF
      samples from 49 patients with multiple sclerosis (MS), chronic inflammatory
      demyelinating polyneuropathy (CIDP), and non-inflammatory neurologic disorders
      (NIND) as controls were submitted to protein expression profiles of 47
      inflammatory biomarkers by multiplex Luminex bead assay to investigate possible
      differences in the inflammatory process for MS and CIDP. RESULTS: Our results
      showed differences in CSF cytokine levels in MS and CIDP; in particular, IL12
      (p40) was significantly highly expressed in MS in comparison with CIDP and NIND,
      while SDF-1alpha and SCGF-beta were significantly highly expressed in CIDP cohort
      when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels
      in NIND if compared with the other groups. CONCLUSIONS: Our study showed that,
      despite some common pathogenic mechanisms, central and peripheral nervous system
      demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory
      soluble proteins in CSF, underlining differences in the immune response involved
      in those autoimmune diseases.

PMID- 29182450
TI  - Infrared studies of deformation and docking in hydrogen-bonded molecular systems.

PMID- 29182449
TI  - Gender interaction of uric acid in the development of hypertension.
AB  - AIM: The present study explored the gender interaction on the risk of uric acid
      in the new development of hypertension. STUDY DESIGN: A longitudinal
      retrospective cohort. SUBJECTS & METHODS: A total of 5,807 individuals with an
      average age of 38 +/- 7 years old were recruited. Individuals whose blood
      pressure rose more than 140/90mmHg or those who newly commenced antihypertensive
      treatment were defined as a new onset of hypertension. Cox regression analysis
      was employed for the analysis. RESULTS: During the 10-years follow-up, 42.8% of
      men and 22.2% of women had developed hypertension. Factors to predict the
      hypertension development were male gender, older age, higher BMI, higher uric
      acid, and higher mean blood pressure. An association between higher uric acid
      levels and higher incidence of hypertension remained statistically significant in
      women in a multivariate model adjusted for various clinical variables (Hazard
      ration (HR), 1.180; 95%CI, 1.018 to 1.369), whereas such association was not
      found in men (HR, 1.034; 95%CI, 0.994 to 1.075). The interaction between the two
      genders reached statistical significance (p for interaction = 0.007). CONCLUSION:
      Higher uric acid is associated with the incident hypertension in the both
      genders. Women are more susceptible to the development of hypertension than men.

PMID- 29182451
TI  - Protein Recommendations for Weight Loss in Elite Athletes: A Focus on Body
      Composition and Performance.
AB  - There exists a large body of scientific evidence to support protein intakes in
      excess of the recommended dietary allowance (RDA) (0.8 g protein/kg/day) to
      promote the retention of skeletal muscle and loss of adipose tissue during
      dietary energy restriction. Diet-induced weight loss with as low as possible
      ratio of skeletal muscle to fat mass loss is a situation we refer to as high
      quality weight loss. We propose that high-quality weight loss is often of
      importance to elite athletes in order to maintain their muscle (engine) and shed
      unwanted fat mass, potentially improving athletic performance. Current
      recommendations for protein intakes during weight loss in athletes are set at 1.6
      2.4 g protein/kg/day. However, the severity of the caloric deficit and type and
      intensity of training performed by the athlete will influence at what end of this
      range athletes choose to be. Other considerations regarding protein intake that
      may help elite athletes achieve weight loss goals include the quality of protein
      consumed, and the timing and distribution of protein intake throughout the day.
      This review highlights the scientific evidence used to support protein
      recommendations for high-quality weight loss and preservation of performance in
      athletes. Additionally, the current knowledge surrounding the use of protein
      supplements, branched chain amino acids (BCAA), beta-hydroxy beta-methylbutyrate
      (HMB), and other dietary supplements with weight loss claims will be discussed.

PMID- 29182452
TI  - Exome Array Analysis of Nuclear Lens Opacity.
AB  - PURPOSE: Nuclear cataract is the most common subtype of age-related cataract, the
      leading cause of blindness worldwide. It results from advanced nuclear sclerosis,
      or opacity in the center of the optic lens, and is affected by both genetic and
      environmental risk factors, including smoking. We sought to understand the
      genetic factors associated with nuclear sclerosis through interrogation of rare
      and low frequency coding variants using exome array data. METHODS: We analyzed
      Illumina Human Exome Array data for 1,488 participants of European ancestry in
      the Beaver Dam Eye Study who were without cataract surgery for association with
      nuclear sclerosis grade, controlling for age and sex. We performed single-variant
      regression analysis for 32,138 variants with minor allele frequency (MAF)
      >=0.003. In addition, gene-based analysis of 11,844 genes containing at least two
      variants with MAF < 0.05 was performed using a gene-based unified burden and non
      burden sequence kernel association test (SKAT-O). Additionally, both single
      variant and gene-based analyses were analyzed stratified by smoking status.
      RESULTS: No single-variant test was statistically significant after Bonferroni
      correction (p < 1.6 * 10-6; top single nucleotide polymorphism (SNP):
      rs144458991, p = 2.83 * 10-5). Gene-based tests were suggestively associated with
      the gene RNF149 overall (p = 8.29 * 10-6) and among never smokers (N = 790, p =
      2.67 * 10-6). CONCLUSIONS: This study did not find a significant genetic
      association with nuclear sclerosis, the possible association with the RNF149 gene
      highlights a potential candidate gene for future studies that aim to understand
      the genetic architecture of nuclear sclerosis.

PMID- 29182453
TI  - Women outperform men in distinguishing between authentic and nonauthentic smiles.
AB  - Women tend to be more accurate in decoding facial expressions than men. We
      hypothesized that women's better performance in decoding facial expressions
      extends to distinguishing between authentic and nonauthentic smiles. We showed
      participants portrait photos of persons who smiled because either they saw a
      pleasant picture (authentic smile) or were instructed to smile by the
      experimenter (nonauthentic smile) and asked them to identify the smiles.
      Participants judged single photos of persons depicting either an authentic or a
      nonauthentic smile, and they judged adjacent photos of the same person depicting
      an authentic smile and a nonauthentic smile. Women outperformed men in
      identifying the smiles when judging the adjacent photos. We discuss implications
      for judging smile authenticity in real life and limitations for the observed sex
      difference.

PMID- 29182454
TI  - Correction to: Li et al., Personalised estimation of a woman's most fertile days.

PMID- 29182456
TI  - Levels of oxidative damage and proinflammatory cytokines are enhanced in patients
      with active vitiligo.
AB  - Vitiligo is an autoimmune depigmenting skin disease characterised by loss of
      melanocytes wherein oxidative stress is proposed to be the initial triggering
      factor with subsequent immune dysregulation. This study aimed to evaluate the
      relationship, if any, between the generation of reactive oxygen species (ROS),
      markers of oxidative damage and circulating cytokines in patients with active
      vitiligo. The generation of ROS in erythrocytes and neutrophils was significantly
      higher in patients with active vitiligo than healthy controls. Alongside, markers
      of oxidative stress-mediated damage namely lipid peroxidation, DNA damage and
      protein carbonylation were evaluated. Patients with active vitiligo demonstrated
      increased lipid and DNA damage but minimal protein damage. There was a
      significant decline in the free radical scavenging capacity of active vitiligo
      cases. A positive correlation existed between baseline levels of ROS and lipid
      peroxidation as also DNA damage. Patients with active vitiligo demonstrated an
      increase in several proinflammatory (IL-6, TNF-alpha, IL-1beta, IFN-gamma and IL
      8) and some anti-inflammatory/immunoregulatory (IL-5 and IL-10) cytokines.
      Importantly, the levels of IFN-gamma and IL-10 consistently correlated with the
      generation of ROS, markers of damage and their free radical scavenging capacity.
      Taken together, patients with active vitiligo demonstrated an enhanced generation
      of ROS in erythrocytes and neutrophils which mediated lipid peroxidation, DNA
      damage and coupled with a decline in their antioxidant capacity created a pro
      oxidant milieu that favoured tissue damage and potential generation of
      neoantigens, accounting for disease progression.

PMID- 29182455
TI  - Isolation of blood-brain barrier-crossing antibodies from a phage display library
      by competitive elution and their ability to penetrate the central nervous system.
AB  - The blood-brain barrier (BBB) is a formidable obstacle for delivery of biologic
      therapeutics to central nervous system (CNS) targets. Whilst the BBB prevents
      passage of the vast majority of molecules, it also selectively transports a wide
      variety of molecules required to maintain brain homeostasis. Receptor-mediated
      transcytosis is one example of a macromolecule transport system that is employed
      by cells of the BBB to supply essential proteins to the brain and which can be
      utilized to deliver biologic payloads, such as antibodies, across the BBB. In
      this study, we performed phage display selections on the mouse brain endothelial
      cell line, bEND.3, to enrich for antibody single-chain variable fragments (scFvs)
      that could compete for binding with a known BBB-crossing antibody fragment, FC5.
      A number of these scFvs were converted to IgGs and characterized for their
      ability to bind to mouse, rat and human brain endothelial cells, and subsequent
      ability to transport across the BBB. We demonstrated that these newly identified
      BBB-targeting IgGs had increased brain exposure when delivered peripherally in
      mice and were also able to transport a biologically active molecule, interleukin
      1 receptor antagonist (IL-1RA), into the CNS. The antagonism of the interleukin-1
      system within the CNS can result in the relief of neuropathic pain. We
      demonstrated that the BBB-targeting IgGs were able to elicit an analgesic
      response in a mouse model of nerve ligation-induced hypersensitivity when fused
      to IL-1RA.

PMID- 29182457
TI  - A Comparison of the Isometric Midthigh Pull and Isometric Squat: Intraday
      Reliability, Usefulness, and the Magnitude of Difference Between Tests.
AB  - PURPOSE: To examine the reliability and usefulness of the isometric midthigh pull
      (IMTP) and isometric squat (ISqT) performed at the same knee and hip angles. The
      scores produced in each test were compared to determine the magnitude of
      differences between tests. METHODS: Twenty-six male and female athletes (age,
      23.6 [4.3] y; height, 1.75 [0.07] m; and body mass, 68.8 [9.7] kg) performed 2
      maximal repetitions of the IMTP and ISqT following a specific warm-up. RESULTS:
      Maximum force, absolute peak force (PF), relative PF, allometrically scaled PF,
      rate of force development (0-200 and 0-250 ms), and impulse (0-300 ms) were
      deemed reliable (intraclass correlation coefficient [ICC] >=.86 and coefficient
      of variation [CV] <=9.4%) in the IMTP and ISqT based on predetermined criteria
      (ICC >=.8 and CV <=10%). Impulse (0-200 and 0-250 ms) was reliable in the ISqT
      (ICC >=.92 and CV <=9.9%). Participants produced significantly (P < .05) greater
      PF and impulse (0-300 ms) during the ISqT compared with the IMTP. When split by
      sex, female participants produced significantly greater PF (P = .042) during the
      ISqT, with no significant differences among male participants (P = .245). Both
      tests are capable of detecting changes in performance in maximum force and
      absolute PF. CONCLUSIONS: Both tests are reliable for non-time-dependent maximal
      strength measures when measured at the same knee and hip angles. The ISqT may be
      preferred when coaches want to test an athlete's true maximum lower-limb
      strength, especially female athletes.

PMID- 29182459
TI  - Recurrent pityriasis rosea: A case report.
AB  - Pityriasis rosea is a papulosquamous skin disorder that occurs most commonly
      between the ages of 10 and 35 years. Recurrent pityriasis rosea is rare. We
      report a patient suffering from recurrent pityriasis rosea, whose etiology may be
      related to either vaccine-induced stimulation of the immune system, or some rare
      vaccine component(influenza A [H1N1] vaccine, hepatitis B vaccine). We believe
      that such a case is unique and it has not been reported previously. The patient
      was successfully treated with a combination of oral cetirizine, a topical steroid
      cream, and narrowband-ultraviolet B phototherapy. The symptoms of this disorder
      should be recognized by dermatologists.

PMID- 29182460
TI  - Balance and Mobility Training With or Without Simultaneous Cognitive Training
      Reduces Attention Demand But Does Not Improve Obstacle Clearance in Older Adults.
AB  - The purpose of this study was to determine whether balance and mobility training
      (BMT) or balance and mobility plus cognitive training (BMT + C) would improve
      obstacle clearance and reaction time (RT); whether further improvements would be
      exposed in the BMT + C group relative to the BMT group; and whether possible
      improvements would be sustained at the follow-up. Healthy older adults were
      allocated to the BMT (n = 15; age: 70.2 +/- 3.2), BMT + C (n = 14; age: 68.7 +/-
      5.5), or control group (n = 13; age: 66.7 +/- 4.2). The BMT and BMT + C groups
      trained one-on-one, three times per week for 12 weeks on a balance obstacle
      course. The BMT + C group also completed cognitive training. Participants walked
      onto and over six obstacles of varying heights while completing no RT, simple RT,
      and choice RT tasks at baseline, posttraining, and at the 12-week follow-up. Both
      the BMT and BMT + C groups improved RT and maintained these improvements at the
      follow-up. No meaningful improvements in obstacle clearance emerged following
      training. Thus, dual-task balance training likely reduces attention demand.

PMID- 29182461
TI  - Diagnosis of multiple endocrine neoplasia type 2B and management of its ocular
      features.
AB  - BACKGROUND: To describe ocular and vascular findings in a patient with multiple
      endocrine neoplasia type 2B. MATERIALS AND METHODS: Case report of a 31-year-old
      male who was referred for ocular assessment following diagnosis of a carotid
      artery dissection and multiple vascular anomalies. RESULTS: Clinical examination
      revealed a marfanoid habitus, myelinated corneal nerve fibers, neuromas in the
      perilimbal area, conjunctival hyperemia with peripheral corneal
      neovascularization, and posterior blepharitis. Diagnosis of multiple endocrine
      neoplasia type 2B was confirmed by genetic testing of the RET proto-oncogene.
      Genetic screening for hereditary aortic and peripheral vasculopathies failed to
      reveal an underlying cause for the vascular findings. We noted improvement of the
      ocular surface disease with topical corticosteroids and oral tetracyclines.
      CONCLUSIONS: Ophthalmologists play a vital role in recognizing this rare but
      lethal malignancy. We report on a patient with apart from characteristic ocular
      findings also staphylococcal hypersensitivity and widespread systemic
      vasculopathy.

PMID- 29182458
TI  - Multimedia Aided Consent for Alzheimer's Disease Research.
AB  - OBJECTIVES: Optimizing the research consent process simultaneously fosters
      respect for autonomy and protection of those with diminished capacity for
      autonomy. This study evaluated the effectiveness of an enhanced research consent
      procedure, employing multimedia disclosure and corrective feedback, in improving
      decisional capacity among 114 people with mild-to-moderate Alzheimer's disease
      (AD) and 134 non-psychiatric comparison (NC) subjects. METHODS: Participants were
      randomized to consent type (routine versus enhanced) and protocol type (lower
      versus higher risk). Outcomes included a 5-item questionnaire assessing immediate
      comprehension, MacArthur Competence Assessment Tool for Clinical Research
      assessing four components of decision-making capacity, and categorical decisional
      capacity (based on a cut-score established in reference to expert judgments for a
      subset of participants). RESULTS: There was no significant effect of the enhanced
      consent procedure, relative to routine consent, on immediate comprehension or
      decisional capacity. CONCLUSIONS: Multimedia tools do not appear to be the
      solution to better consent for AD research. CLINICAL IMPLICATIONS: Given the
      ethical primacy of informed consent and issues of justice for impaired
      populations who might be harmed by an absence of research-based treatment
      advances, continued search for ways to more meaningfully engage people with AD in
      the consent or assent process is warranted.

PMID- 29182463
TI  - Willingness to pay for cataract surgery is much lower than actual costs in
      Zamfara state, northern Nigeria.
AB  - PURPOSE: Direct medical and non-medical costs incurred by those undergoing
      subsidised cataract surgery at Gusau eye clinic, Zamfara state, were recently
      determined. The aim of this study was to assess the willingness to pay for
      cataract surgery among adults with severe visual impairment or blindness from
      cataract in rural Zamfara and to compare this to actual costs. METHODS: In three
      rural villages served by Gusau eye clinic, key informants helped identify 80
      adults with bilateral severe visual impairment or blindness (<6/60), with
      cataract being the cause in at least one eye. The median amount participants were
      willing to pay for cataract surgery was determined. The proportion willing to pay
      actual costs of the (i) subsidised surgical fee (US$18.5), (ii) average non
      medical expenses (US$25.2), and (iii) average total expenses (US$51.2) at Gusau
      eye clinic were calculated. Where participants would seek funds for surgery was
      determined. RESULTS: Among 80 participants (38% women), most (n = 73, 91%) were
      willing to pay something, ranging from <US$1 to US$186 (median US$18.5,
      interquartile range 6.2-31.1). Approximately half of the participants (n = 41)
      were willing to pay US$18.5 (78% men), one-third (n = 26) were willing to pay
      US$25.2 (77% men); and 11% (n = 9) were willing to pay US$51.2 (all men). Only
      six participants (8%) already had the money to pay; one quarter (n = 20) would
      need to sell possessions to raise the funds. CONCLUSION: Willingness to pay for
      cataract surgery among adults with operable cataract in rural Zamfara state is
      far lower than current costs of undergoing surgery. People who were widowed-most
      of whom were women-were willing to pay least. Further financial support is
      required for cataract surgery to be universally accessible.

PMID- 29182465
TI  - Author's response to: "Letter to the Editor" regarding content of "Mesothelioma
      from asbestos exposures: Epidemiologic patterns and impact in the United States"
      by R. A. Lemen, Journal of Toxicology and Environmental Health, Part B 2016; 19:
      250-265.

PMID- 29182466
TI  - Two Agrobacterium tumefaciens CheW Proteins Are Incorporated into One
      Chemosensory Pathway with Different Efficiencies.
AB  - Agrobacterium tumefaciens is the agent that causes crown gall tumor disease on
      more than 140 species of dicotyledonous plants. Chemotaxis of A. tumefaciens
      toward the wound sites of the host plant is the first step to recognize the host.
      CheW is a coupling protein that bridges the histidine kinase CheA and the
      chemoreceptors to form the chemotaxis core signaling complex and plays a crucial
      role in the assembly and function of the large chemosensory array. Unlike all
      previously reported chemotaxis systems, A. tumefaciens has only one major che
      operon but two cheW homologs (atu2075 as cheW1 and atu2617 as cheW2) on unlinked
      loci. The in-frame deletion of either cheW gene significantly affects A.
      tumefaciens chemotaxis but does not abolish the chemotaxis, unless both cheW
      genes were deleted. The effect of cheW2 deletion on the chemotaxis is more severe
      than that of cheW1 deletion. Either CheW can interact with CheA and couple it to
      the cell poles. The promoter activity of cheW2 is always higher than that of
      cheW1 under all of the tested conditions. When two cheW genes were adjusted to
      the same expression level by using the identical promoter, the difference between
      the effects of two CheW proteins on the chemotaxis still existed. Therefore, we
      envision that both the different molecular ratio of two CheW proteins in cell and
      the different affinities of two CheW proteins with CheA and chemoreceptors result
      in the efficiency difference of two CheW proteins in functioning in the large
      chemosensory array.

PMID- 29182464
TI  - Triclosan exposure, transformation, and human health effects.
AB  - Triclosan (TCS) is an antimicrobial used so ubiquitously that 75% of the US
      population is likely exposed to this compound via consumer goods and personal
      care products. In September 2016, TCS was banned from soap products following the
      risk assessment by the US Food and Drug Administration (FDA). However, TCS still
      remains, at high concentrations, in other personal care products such as
      toothpaste, mouthwash, hand sanitizer, and surgical soaps. TCS is readily
      absorbed into human skin and oral mucosa and found in various human tissues and
      fluids. The aim of this review was to describe TCS exposure routes and levels as
      well as metabolism and transformation processes. The burgeoning literature on
      human health effects associated with TCS exposure, such as reproductive problems,
      was also summarized.

PMID- 29182468
TI  - Serum sMICA as biomarker in detection of non-small-cell lung carcinoma.

PMID- 29182467
TI  - Farming and mortality rates attributed to non-Hodgkin's lymphoma in Taiwan.
AB  - Previous studies suggested an elevated risk of non-Hodgkin's lymphoma (NHL) among
      farmers. To date, no apparent study examined the association between farming and
      NHL in Asian countries. The aim of this study was to investigate whether farmers
      in Taiwan exhibited an increased risk of mortality attributed to NHL. To this
      end, a mortality odds ratio (MOR) study was conducted to estimate the relative
      risk of mortality attributed to NHL for farmers in Taiwan. Data on the decedents
      enrolled in this investigation were derived from the death certificate database
      for the period 1997-2009. The study group comprised individuals who died from NHL
      and who were 50 years or older. The control group consisted of subjects who died
      from all other causes, excluding cancers, in the corresponding age group.
      Multiple logistic regression analysis was performed to compute the MOR, with
      adjustments for gender, age at death, year of death, marital status, and
      urbanizational levels. Among 32,456 deceased farmers, 205 died due to NHL.
      Farmers were found to have a nonsignificantly higher MOR than nonfarmers. This
      risk estimate is similar to estimates in previous meta-analyses. The MOR for NHL
      was higher among farmers who died 65 years or older than among those who died at
      younger ages. The findings indicate that farming in Taiwan may increase the risk
      of death attributed to NHL. Exposure to pesticides might be an influential factor
      contributing to high risk of mortality attributed to NHL among farmers and
      therefore needs to be further investigated.

PMID- 29182469
TI  - Semistructured Observation of Population-based Eye Screening in The Netherlands.
AB  - BACKGROUND: In the Netherlands, youth-healthcare (YHC) physicians screen children
      7 times for vision disorders between the ages of 1 and 60 months. Examination
      consists of inspection of the external structures of the eye, fundus red reflex,
      Hirschberg test, pupillary reflexes, cover-uncover test, alternating-cover test,
      eye motility, monocular pursuit, and, from 36 months onwards, visual acuity (VA).
      We observed how well these tests are done. METHODS: Screening test performance
      was assessed with semistructured observations. Two orthoptic students developed a
      semistructured observation form. In addition to extensive instructions from an
      orthoptist and YHC-physicians instructor, they attended 2 one-day courses for YHC
      physicians. Tests were assessed using criteria based on the Dutch Child Vision
      Screening Guideline version 2010 and the Dutch Manual for Orthoptic Examination.
      Type of chart, testing distance, and starting eye were recorded for VA
      measurements. The observations in the first week were done simultaneously by the
      two observers and checked for concordance. RESULTS: Concordance between the two
      observers was good. Twenty-five YHC physicians were observed during 100 days in
      total. Two physicians were excluded because they examined few children. The
      remaining 23 physicians examined 329 children, of whom 82 were aged 1-4 months,
      157 aged 6-24 months, and 90 aged 36-45 months of age. Fundus red reflex was
      performed in 89% of children, Hirschberg test in 88%, pupillary reflexes in 14%,
      cover-uncover test in 65%, alternating-cover test in 62%, eye motility in 68%,
      monocular pursuit in 23%, and VA at 36-45 months in 94%. Forty-eight percent of
      cover-uncover tests, 36% of alternating-cover tests, and 7% of eye motility tests
      were performed correctly. VA was measured at 3 meters in 2%, others at 5 meters
      in accordance with the guideline. A picture chart was used instead of the Landolt
      C at the age of 45 months in 23%. VA measurements were performed correctly in
      89%, fundus red reflex in 89%, and Hirschberg test in 87%. CONCLUSION: Hirschberg
      test, fundus red reflex, and VA were adequately tested in most cases. Cover
      uncover test, alternating-cover test, and eye motility were often performed
      inadequately. Pupillary reflexes were skipped often as room lights could not be
      dimmed.

PMID- 29182471
TI  - A Model for Temporal Dynamics of Brown Rot Spreading in Fruit Orchards.
AB  - Brown rot, caused by Monilinia spp., is a major disease of stone fruit and, in
      favorable environmental conditions and in the absence of fungicide treatments, it
      causes important economic losses. In the present work, we propose a modification
      of classical susceptible, exposed, infectious and removed compartmental models to
      grasp the peculiarities of the progression of brown rot epidemics in stone fruit
      orchards in the last stage of the fruit growth (i.e., from the end of the pit
      hardening to harvest time). Namely, we took into account (i) the lifespan of
      airborne spores; (ii) the dependence of the latent period on the cuticle crack
      surface area, which itself varies in time with fruit growth; (iii) the
      impossibility of recovery in infectious fruit; and (iv) the abrupt interruption
      of disease development by the elimination of the host fruit at harvest time. We
      parametrized the model by using field data from a peach Prunus persica orchard
      infected by Monilinia laxa and M. fructicola in Avignon (southern France). The
      basic reproduction number indicates that the environmental conditions met in the
      field were extremely favorable to disease development and the model closely
      fitted the temporal evolution of the fruit abundance in the different
      epidemiological compartments. The model permits us to highlight crucial
      mechanisms undergoing brown rot build up and to evaluate the consequences of
      different agricultural practices on the quantity and quality of the yield. We
      found that winter sanitation practices (which decrease the initial infection
      incidence) and the control of the fruit load (which affects the host fruit
      density and the single fruit growth trajectory) can be effective in controlling
      brown rot in conjunction with or in place of fungicide treatments.

PMID- 29182470
TI  - High shear induces platelet dysfunction leading to enhanced thrombotic propensity
      and diminished hemostatic capacity.
AB  - Thrombosis and bleeding are devastating adverse events in patients supported with
      blood-contacting medical devices (BCMDs). In this study, we delineated that high
      non-physiological shear stress (NPSS) caused platelet dysfunction that may
      contribute to both thrombosis and bleeding. Human blood was subjected to NPSS
      with short exposure time. Levels of platelet surface GPIbalpha and GPVI receptors
      as well as activation level of GPIIb/IIIa in NPSS-sheared blood were examined
      with flow cytometry. Adhesion of sheared platelets on fibrinogen, von Willibrand
      factor (VWF), and collagen was quantified with fluorescent microscopy. Ristocetin
      and collagen-induced platelet aggregation was characterized by aggregometry.
      NPSS activated platelets in a shear and exposure time-dependent manner. The
      number of activated platelets increased with increasing levels of NPSS and
      exposure time, which corresponded well with increased adhesion of sheared
      platelets on fibrinogen. Concurrently, NPSS caused shedding of GPIbalpha and GPVI
      in a manner dependent on shear and exposure time. The loss of intact GPIbalpha
      and GPVI increased with increasing levels of NPSS and exposure time. The number
      of platelets adhered on VWF and collagen decreased with increasing levels of NPSS
      and exposure time, respectively. The decrease in the number of platelets adhered
      on VWF and collagen corresponded well with the loss in GPIbalpha and GPVI on
      platelet surface. Both ristocetin- and collagen-induced platelet aggregation in
      sheared blood decreased with increasing levels of NPSS and exposure time. The
      study clearly demonstrated that high NPSS causes simultaneous platelet activation
      and receptor shedding, resulting in a paradoxical effect on platelet function via
      two distinct mechanisms. The results from the study suggested that the NPSS could
      induce the concurrent propensity for both thrombosis and bleeding in patients.

PMID- 29182472
TI  - An Innovative Root Inoculation Method to Study Ralstonia solanacearum
      Pathogenicity in Tomato Seedlings.
AB  - In this study, we report Ralstonia solanacearum pathogenicity in the early stages
      of tomato seedlings by an innovative root inoculation method. Pathogenicity
      assays were performed under gnotobiotic conditions in microfuge tubes by
      employing only 6- to 7-day-old tomato seedlings for root inoculation. Tomato
      seedlings inoculated by this method exhibited the wilted symptom within 48 h and
      the virulence assay can be completed in 2 weeks. Colonization of the wilted
      seedlings by R. solanacearum was confirmed by using gus staining as well as
      fluorescence microscopy. Using this method, mutants in different virulence genes
      such as hrpB, phcA, and pilT could be clearly distinguished from wild-type R.
      solanacearum. The method described here is economic in terms of space, labor, and
      cost as well as the required quantity of bacterial inoculum. Thus, the newly
      developed assay is an easy and useful approach for investigating virulence
      functions of the pathogen at the seedling stage of hosts, and infection under
      these conditions appears to require pathogenicity mechanisms used by the pathogen
      for infection of adult plants.

PMID- 29182473
TI  - Data-mining analysis of the provision of mobility devices in the United States
      with emphasis on complex rehab technology.
AB  - The objective of this study was to describe the provision of wheeled-mobility
      equipment from the perspective of a large equipment supplier in the United
      States. The records of clients who were prescribed a mobility device over a 6
      month period were randomly sampled to product a dataset of 1,689 clients.
      Analysis was limited to descriptive statistics and measures of relationships. The
      majority of the clients were adults (72%) and female (58%) with 62% receiving a
      manual wheelchair. The majority of interventions (58%) included some contribution
      from the client or client's family. Overall, 86% of all prescribed wheelchairs
      were classified as complex rehab technology (CRT). About half (52%) of all
      interventions involved a therapist. Therapist involvement was 2.5 times more
      likely during CRT interventions compared to standard durable medical equipment
      (StdDME). The project provides a novel description of mobility-related equipment
      provision using a large retrospective dataset. The analysis demonstrates the
      utility of analyzing a large number of client interventions. The capabilities of
      such analyses have business, clinical, and policy implications. Combining the
      data available from suppliers with prospective collection of client-specific
      information, such as outcomes, would be a more powerful means to assess the
      provision of wheeled-mobility equipment.

PMID- 29182474
TI  - Disordered eating and insulin restriction in type 1 diabetes: A systematic review
      and testable model.
AB  - AIM: To provide an overview of the existing literature pertaining to insulin
      restriction as a disordered eating behaviour in individuals with type 1 diabetes
      and present a novel maintenance model: The Transdiagnostic Model of Disordered
      Eating in Type 1 Diabetes. METHOD: A systematic review was conducted of the
      current literature relevant to insulin restriction and/or omission in the context
      of disordered eating in type 1 diabetes. A new maintenance model was then
      developed by incorporating diabetes-specific factors into existing eating
      disorder models. RESULTS: Type 1 diabetes may complicate the development and
      maintenance of disordered eating behaviour. Diabetes-specific circumstances,
      including disease diagnosis, insulin management, insulin restriction, and
      diabetes-related complications, contribute to the maintenance of disordered
      eating cognitions and behaviours. DISCUSSION: The proposed model offers a
      comprehensive representation of insulin restriction as a disordered eating
      behaviour in type 1 diabetes. Future research should test the model to further
      understand the mechanisms underlying disordered eating in type 1 diabetes and
      inform treatments for this at-risk population.

PMID- 29182476
TI  - Practice wisdom and research-based knowledge: Never the twain shall meet?

PMID- 29182477
TI  - Detection of Plasmid-Mediated Colistin Resistance, mcr-1 and mcr-2 Genes, in
      Salmonella spp. Isolated from Food at Retail in Belgium from 2012 to 2015.
AB  - A collection of 105 colistin-resistant Salmonella isolates collected from 2012 to
      2015 in the national surveillance program in Belgium was screened by PCR for the
      presence of genes mcr-1 and mcr-2. Of these, 1.90% (2/105) and 0.95% (1/105)
      tested positive for mcr-1 and mcr-2, respectively. The presence of the mcr-1 or
      mcr-2 determinant has been confirmed by whole genome sequencing and allowed the
      localization of these two genes on IncX4 type plasmids. We report here the
      presence of mcr-1 and the first mcr-2 gene in Salmonella ever isolated in the
      Belgian food chain. Although present at retail since 2012, the occurrence is low
      and sporadic.

PMID- 29182478
TI  - Bereavement Challenges and Their Relationship to Physical and Psychological
      Adjustment to Loss.
AB  - OBJECTIVE: The psychosocial challenges confronted by bereaved survivors may
      contribute to poor bereavement adjustment. Measures of the challenges of
      bereavement are limited. This study is a preliminary examination of the factor
      structure of a new measure of bereavement challenges and their relationships to
      quality of life and mental illness in bereaved cancer caregivers. This measure
      was designed to identify intervention targets to reduce the likelihood of
      prolonged grief. METHODS: Caregivers of advanced cancer patients were
      administered measures of bereavement challenges (Bereavement Challenges Scale,
      BCS), quality of life (Medical Outcomes Study Short Form-36), prolonged grief (PG
      13), and mental disorders (Structured Clinical Interview for the DSM-IV).
      Principal component factor analyses identified the underlying factor structure of
      the BCS. We examined associations between the factors and caregiver quality of
      life, prolonged grief, and rates of mental disorders. RESULTS: A factor analysis
      identified five factors: "Challenges with Connecting with Others," "Challenges
      with Change," "Challenges Imagining a Hopeful Future," "Challenges with Accepting
      the Loss," and "Challenges with Guilt." Greater endorsement of bereavement
      challenges was associated with worse quality of life, more severe symptoms of
      prolonged grief, and greater likelihood of meeting criteria for a mental
      disorder. CONCLUSIONS: Assessing the challenges associated with bereavement is
      important to understanding barriers to bereaved individuals' adjustment. The five
      factors of the BCS point to potential targets for clinical intervention.
      Additional research on the BCS is needed, including validation in larger more
      diverse samples, and confirmation that reduction of these challenges is
      associated with less psychiatric morbidity and, specifically, symptoms of
      prolonged grief.

PMID- 29182479
TI  - Vaccination choices for older people, looking beyond age specific approaches.
AB  - INTRODUCTION: To improve the ability of vaccines to protect older individuals we
      can no longer consider those over 65 years of age to be an homogenous population
      termed the 'elderly' displaying a condition termed immunosenescence. Area
      Covered: The most recent figures from the US Census Bureau indicate that the
      global population exceeds 7,400 million. Of these more than 657 million are
      currently over 65, an age often designated by policy makers as permitting them
      access to concessions, pensions and social care benefits. But the spill-over
      consequences of these policies are the impact they have on access to different
      vaccine formulations. Aging is associated with a blunted immune system, often
      termed immunosenescence, and because those of 65 are considered old, by
      association they are thought to have reduced immunity. Consequently, different
      vaccines are offered to those over this age. Expert Commentary: We believe it to
      be an inappropriate policy to ascribe a biological condition and consequent
      vaccine choices, to a population on the basis of single chronological feature. To
      ensure better protection within this population we need to consider approaches to
      stratify this group to ensure the best vaccine choices.

PMID- 29182480
TI  - Evaluation of State Plans and the Livestock Emergency Response Plan (LERP).
AB  - The Livestock Emergency Response Plan (LERP) was published in 2014 as a toolkit
      to assist state agricultural emergency planners in writing or modifying state
      foreign animal disease/high-consequence disease (FAD/HCD) plans. This research
      serves as a follow-up to and expands on an initial survey conducted in 2011 by
      the Department of Homeland Security Office of Health Affairs, Food, Ag, and
      Veterinary Defense Branch. The purpose of this project is to describe the status
      of current state animal disease response plans in relation to how closely their
      content, order, and terminology relate to that described in the LERP template.
      The analysis was compared to the 2011 study to identify advances, trends,
      continued areas for increased alignment, and fulfillment of planning gaps in
      individual state plans. While vast improvements were made in the status of state
      animal disease response plans from 2011 to 2016, there is nonetheless significant
      room for enhancing consistency between and identifying gaps in FAD/HCD plans. As
      awareness of the LERP toolkit grows, the authors hope its use as a template by
      the states will expand accordingly, thereby increasing consistency between plans
      and more thoroughly addressing challenges in an FAD/HCD outbreak. The results of
      this study support the need for curriculum planning resources at the state level.
      Development of a training curriculum and planning workshops for state agriculture
      emergency planners will produce a consistent planning philosophy and skill set
      among state planners-another means of indirectly addressing current planning gaps
      in agricultural emergency response.

PMID- 29182481
TI  - The Use of Therapeutic Hypothermia in Neonates with Perinatal Asphyxia at
      Charlotte Maxeke Johannesburg Academic Hospital: A Retrospective Review.
AB  - Therapeutic hypothermia (TH) has become the standard of care to reduce
      neurological damage following perinatal asphyxia. Current recommendations call
      for implementation of a standard, evidence-based protocol for the provision of
      TH. This is particularly challenging in resource-limited settings. This is a
      retrospective, descriptive study to determine whether neonates at Charlotte
      Maxeke Johannesburg Academic Hospital (CMJAH) are receiving TH according to the
      unit protocol in place. The study included all neonates with a birth weight
      greater than 1800 g admitted to the CMJAH neonatal unit from January 1, 2013, to
      June 30, 2017, before 24 hours of life. Neonates were assessed as to whether they
      met the criteria for TH according to the protocol, and reasons for not providing
      TH to those who qualified were investigated. The total number of neonates
      enrolled for the study was 485. Three hundred patients met the criteria for TH.
      185/300 appropriately received TH. One hundred fifteen patients were not cooled,
      despite meeting TH criteria. Reasons for this included severe clinical conditions
      (73/115) and a lack of equipment (26/115). Of the remaining 185 patients who did
      not meet TH criteria, 21 patients inappropriately received TH. A total of 206
      neonates received TH. TH at CMJAH is largely being practiced as per protocol.
      Still, more resources are needed, not only to optimize the number of patients who
      have access to this treatment modality but also in terms of imaging and support
      strategies.

PMID- 29182482
TI  - Endoscopic Plantar Fasciotomy vs Open Radiofrequency Microtenotomy for
      Recalcitrant Plantar Fasciitis.
AB  - BACKGROUND: Although usually self-limiting, around 10% of patients develop
      recalcitrant plantar fasciitis despite conservative treatment. In such cases,
      operative intervention can be offered. Traditionally, plantar fasciotomy has been
      the treatment of choice, but recently, there has been a push for more minimally
      invasive approaches. Radiofrequency microtenotomy has also been increasingly used
      as a treatment option. In this study, we compare the outcomes of endoscopic
      plantar fasciotomy and open radiofrequency microtenotomy. METHODS: Patients
      treated in our institution with either procedure between 2007 and 2015 were
      included and interviewed at baseline and 3 months, 6 months, and 12 months
      postoperatively using the American Orthopaedic Foot & Ankle Society (AOFAS) and
      36-item Medical Outcomes Short Form (SF-36) questionnaires. They were asked
      questions to evaluate their expectation and satisfaction postoperatively.
      Demographic and clinicopathological data were prospectively collected from
      clinical charts and electronic records. RESULTS: There was no difference in
      either treatment arms preoperatively and an overall improvement in all functional
      outcomes postoperatively. However, patients who had endoscopic plantar fasciotomy
      fared better at 3 months compared to patients who underwent open microtenotomy
      with the visual analog score component of the AOFAS hindfoot score (HINDVAS) and
      the social functioning and role-functioning-emotional reaching statistical
      significance ( P = .027, P = .03, and P = .03, respectively). There was no
      difference in functional outcomes at 6 or 12 months postoperatively. CONCLUSION:
      Endoscopic plantar fasciotomy was associated with an earlier improvement in
      functional outcome in our study. However, both treatments had equivalent outcomes
      at 1-year follow-up, suggesting that either method is reasonable in the treatment
      of chronic plantar fasciitis. LEVEL OF EVIDENCE: Level III, comparative study.

PMID- 29182483
TI  - Harmonizing the Nomenclature for Therapeutic Aerosol Particle Size: A Proposal.

PMID- 29182484
TI  - PPARgamma Regulates Mitochondrial Structure and Function and Human Pulmonary
      Artery Smooth Muscle Cell Proliferation.
AB  - Pulmonary hypertension (PH) is a progressive disorder that causes significant
      morbidity and mortality despite existing therapies. PH pathogenesis is
      characterized by metabolic derangements that increase pulmonary artery smooth
      muscle cell (PASMC) proliferation and vascular remodeling. PH-associated
      decreases in peroxisome proliferator-activated receptor gamma (PPARgamma)
      stimulate PASMC proliferation, and PPARgamma in coordination with PPARgamma
      coactivator 1alpha (PGC1alpha) regulates mitochondrial gene expression and
      biogenesis. To further examine the impact of decreases in PPARgamma expression on
      human PASMC (HPASMC) mitochondrial function, we hypothesized that depletion of
      either PPARgamma or PGC1alpha perturbs mitochondrial structure and function to
      stimulate PASMC proliferation. To test this hypothesis, HPASMCs were exposed to
      hypoxia and treated pharmacologically with the PPARgamma antagonist GW9662 or
      with siRNA against PPARgamma or PGC1alpha for 72 hours. HPASMC proliferation
      (cell counting), target mRNA levels (qRT-PCR), target protein levels (Western
      blotting), mitochondria-derived H2O2 (confocal immunofluorescence), mitochondrial
      mass and fragmentation, and mitochondrial bioenergetic profiling were determined.
      Hypoxia or knockdown of either PPARgamma or PGC1alpha increased HPASMC
      proliferation, enhanced mitochondria-derived H2O2, decreased mitochondrial mass,
      stimulated mitochondrial fragmentation, and impaired mitochondrial bioenergetics.
      Taken together, these findings provide novel evidence that loss of PPARgamma
      diminishes PGC1alpha and stimulates derangements in mitochondrial structure and
      function that cause PASMC proliferation. Overexpression of PGC1alpha reversed
      hypoxia-induced HPASMC derangements. This study identifies additional mechanistic
      underpinnings of PH, and provides support for the notion of activating PPARgamma
      as a novel therapeutic strategy in PH.

PMID- 29182485
TI  - On Bearing Witness.

PMID- 29182486
TI  - Two New Species of Staphylocystoides Yamaguti, 1959 (Cyclophyllidea:
      Hymenolepididae) from the Masked Shrew Sorex cinereus in North America.
AB  - Two new species of Staphylocystoides are described from masked shrews Sorex
      cinereus. Staphylocystoides oligospinosus n. sp. was collected from the vicinity
      of Missoula, Montana, United States, and Staphylocystoides parasphenomorphus n.
      sp. was collected from the vicinity of Whitehorse, Yukon Territory, Canada.
      Morphological differentiation from known species is provided. Both species are
      morphologically closest to Staphylocystoides sphenomorphus and to each other.
      Among other characters, S. oligospinosus n. sp. can be easily differentiated from
      all known species of the genus by unique cirrus armature, which consists of a
      short zone of small spines at the base of the cirrus, a few large sparsely
      distributed spines of varying size in the middle part of the cirrus, and hair
      like microtriches densely covering the apical portion of the cirrus.
      Staphylocystoides parasphenomorphus n. sp. differs from S. oligospinosus n. sp.
      in a number of characters, most distinctly in cirrus armature, and from another
      morphologically similar species, S. sphenomorphus, in the number of proglottids,
      strobila size, number and size of rostellar hooks, and relative length of cirrus
      sac. Comparison of partial sequences of nuclear large ribosomal RNA subunit gene
      (1,310 base pairs [bp]) and mitochondrial NAD(P)H dehydrogenase subunit 1 gene
      (710 bp) strongly supports the status of the described forms as new species. This
      increases the number of Staphylocystoides species known in North America to 9 (5
      parasitizing S. cinereus) and the total number of species in the genus to 12.
      Staphylocystoides parasphenomorphus n. sp. is the first named Staphylocystoides
      record in Canada.

PMID- 29182488
TI  - The Influence of Prosthesis Design on the Outcomes of Tooth Implants Immediately
      Placed and Loaded by Means of One-Piece Titanium Machined Restoration.
AB  - Our purpose was to evaluate the occurrence of complications and the degree of
      bone loss in a cohort of patients treated with fixed prostheses supported by
      immediately loaded dental implants. The primary aim was to compare partial versus
      full-arch fixed dental prostheses. We then tested the effect of sinus lifting. In
      the present retrospective cohort study, the patients had their implants restored
      with fixed dental prostheses supported by dental implants positioned in the
      posterior maxilla and mandible. When necessary, the maxillary sinuses were
      grafted with particulate autogenous bone. Patients were then ranked according to
      the following predictors: length of prosthesis, crown-to-implant ratio, number of
      crowns to number of implants ratio, and presence of sinus lifting. Outcomes were
      evaluated for up to 2 years regarding the peri-implant marginal bone loss and
      implant/prosthesis survival rates. Fifty-eight subjects (209 implants) were
      rehabilitated with 25 fixed full-arch prostheses and 33 partial fixed dental
      implant bridges (16 supported by implants placed in grafted sinus). The mean
      marginal bone loss for implants supporting partial fixed dental prostheses
      amounted to 0.81 mm, whereas that for implants within the group of full-arch
      fixed dental prostheses was 1.21 mm; the comparison of the levels in the 2 groups
      showed a significant difference ( P = .0055). A statistically significant
      difference ( P = .0006) was found between the bone loss around maxillary implants
      (1.53 mm) and the bone loss around mandibular implants (1.10 mm). Two implants
      and 4 prostheses failed; 2-year survival rates of partial and of full-arch fixed
      dental prostheses, respectively, were 94.1% and 96%. Bone loss in full-arch
      prostheses appeared to be higher than in that of partial prosthesis. Implant
      supported prostheses in the maxillae exhibited a bone loss higher than that
      registered in mandibles.

PMID- 29182487
TI  - Using Electronic Health Records for Quality Measurement and Accountability in
      Care of the Seriously Ill: Opportunities and Challenges.
AB  - BACKGROUND: As our population ages and the burden of chronic illness rises, there
      is increasing need to implement quality metrics that measure and benchmark care
      of the seriously ill, including the delivery of both primary care and specialty
      palliative care. Such metrics can be used to drive quality improvement, value
      based payment, and accountability for population-based outcomes. METHODS: In this
      article, we examine use of the electronic health record (EHR) as a tool to assess
      quality of serious illness care through narrative review and description of a
      palliative care quality metrics program in a large healthcare system. RESULTS: In
      the search for feasible, reliable, and valid palliative care quality metrics, the
      EHR is an attractive option for collecting quality data on large numbers of
      seriously ill patients. However, important challenges to using EHR data for
      quality improvement and accountability exist, including understanding the
      validity, reliability, and completeness of the data, as well as acknowledging the
      difference between care documented and care delivered. Challenges also include
      developing achievable metrics that are clearly linked to patient and family
      outcomes and addressing data interoperability across sites as well as EHR
      platforms and vendors. This article summarizes the strengths and weakness of the
      EHR as a data source for accountability of community- and population-based
      programs for serious illness, describes the implementation of EHR data in the
      palliative care quality metrics program at the University of Washington, and,
      based on that experience, discusses opportunities and challenges. Our palliative
      care metrics program was designed to serve as a resource for other healthcare
      systems. DISCUSSION: Although the EHR offers great promise for enhancing quality
      of care provided for the seriously ill, significant challenges remain to
      operationalizing this promise on a national scale and using EHR data for
      population-based quality and accountability.

PMID- 29182489
TI  - Peri-implantitis: A Comprehensive Overview of Systematic Reviews.
AB  - The objective of this systematic review was to perform a comprehensive overview
      of systematic reviews and meta-analyses pertaining to peri-implantitis in humans,
      including the prevalence and incidence, the diagnostic findings, microbial
      findings, effects of systemic diseases, and treatment of peri-implantitis.
      Electronic databases were searched for systematic reviews and meta-analyses of
      peri-implantitis. In view of the limitations of the included systematic reviews,
      the outcome of this overview suggested that (1) occurrence of peri-implantitis
      was higher in patients with periodontitis, in patients who smoke, and after 5
      years of implant function; (2) the microbial profile of peri-implantitis was
      different from periodontitis; (3) risk for peri-implantitis was higher in
      patients with uncontrolled diabetes and cardiovascular disease; (4) there was no
      strong evidence to suggest the most effective treatment intervention for peri
      implantitis, although most peri-implantitis treatments can produce successful
      outcomes; and (5) postimplant maintenance may be crucial in patients with a high
      risk of peri-implantitis.

PMID- 29182490
TI  - Positive Margins by Oropharyngeal Subsite in Transoral Robotic Surgery for T1/T2
      Squamous Cell Carcinoma.
AB  - Objective To compare positive margin rates between the 2 most common subsites of
      oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the
      tonsil, as well as identify preoperative imaging characteristics that predispose
      toward positive margins. Study Design Case series with chart review. Setting
      Tertiary care referral center. Subjects and Methods We compared the final and
      intraoperative positive margin rate between TORS resections for tonsil and BOT
      oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins
      on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT
      tumors to measure their dimensions and patterns of spread and provided a
      prediction of final margin results. Results Between January 2010 and May 2016, a
      total of 254 patients underwent TORS for OPSCC. A total of 140 patients who
      underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is
      significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%,
      respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil
      tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10
      times more likely to receive chemoradiation compared to a negative margin,
      controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95%
      confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and
      subjective radiologic examination of BOT tumors did not correlate with final
      margin status. Conclusion Positive margins are significantly more likely during
      TORS BOT resections compared to tonsil resections. More research is needed to
      help surgeons predict which T1/T2 tumors will be difficult to completely
      extirpate.

PMID- 29182491
TI  - Improved Lung Function after Sinus Surgery in Cystic Fibrosis Patients with
      Moderate Obstruction.
AB  - Objectives Cystic fibrosis (CF) is characterized by infection and inflammation of
      the sinorespiratory tract. Functional endoscopic sinus surgery (FESS) is an
      option for patients with severe sinusitis. We sought to evaluate pulmonary
      function testing after FESS in pediatric and adult patients with CF. Study Design
      Retrospective chart review using data from all patients with CF who underwent
      FESS from January 2009 to July 2014. Setting Patients were from a single
      institution. Subjects and Methods Data were extracted for 181 patients and 320
      surgeries. Lung function data, including the forced expiratory volume in one
      second (FEV1), forced vital capacity (FVC), and FEV1/FVC, were retrieved within 1
      year before and after surgery. Mixed-effects regression was used to compare FEV1
      trajectories before and after surgery. The effect of surgery was stratified by
      presurgery FEV1 to compare patients with mild/no lung disease (FEV1 >80%) and
      moderate/severe lung disease (FEV1 <80%). Results Of the 181 patients reviewed,
      131 with primary FESS had FEV1 data. Presurgery average age was 16 years (95%
      confidence interval [CI], 14.27-17.73), and FEV1 mean was 85% (95% CI, 81.02
      88.98). There were 88 patients with FEV1 >80% and 43 patients with FEV1 <80%. For
      the entire cohort, lung function did not change related to FESS. Among patients
      with FEV1 <80%, FEV1 declined presurgery by 3.5% per year (95% CI, -6.1% to 
      0.8%; P = .010), which halted after surgery with these patients, then showing no
      subsequent change in FEV1 (95% CI, 0.9%-3.7%; P = .240). No benefit was
      identified for patients with FEV1 >80%. Conclusion Pulmonary function testing
      improved in patients with moderate/severe lung disease 1 year following FESS.
      This suggests FESS may benefit pulmonary outcomes.

PMID- 29182492
TI  - Platelet Transfusion for Patients With Cancer: American Society of Clinical
      Oncology Clinical Practice Guideline Update Summary.

PMID- 29182493
TI  - Japan's 2014 General Election: Political Bots, Right-Wing Internet Activism, and
      Prime Minister Shinzo Abe's Hidden Nationalist Agenda.
AB  - In this article, we present results on the identification and behavioral analysis
      of social bots in a sample of 542,584 Tweets, collected before and after Japan's
      2014 general election. Typical forms of bot activity include massive Retweeting
      and repeated posting of (nearly) the same message, sometimes used in combination.
      We focus on the second method and present (1) a case study on several patterns of
      bot activity, (2) methodological considerations on the automatic identification
      of such patterns and the prerequisite near-duplicate detection, and (3) we give
      qualitative insights into the purposes behind the usage of social/political bots.
      We argue that it was in the latency of the semi-public sphere of social media-and
      not in the visible or manifest public sphere (official campaign platform, mass
      media)-where Shinzo Abe's hidden nationalist agenda interlocked and overlapped
      with the one propagated by organizations such as Nippon Kaigi and Internet right
      wingers (netto uyo) during the election campaign, the latter potentially forming
      an enormous online support army of Abe's agenda.

PMID- 29182494
TI  - Food Insecurity and Obesity: Exploring the Role of Social Support.
AB  - BACKGROUND: Women are disproportionately affected by both obesity and food
      insecurity. Food insecurity occurs when there is limited ability to acquire
      adequate foods. It is unknown whether social support can reduce the effect of
      food insecurity on increased obesity. This study seeks to determine whether
      social support modifies the relationship between food insecurity and obesity.
      METHODS: We conducted a cross-sectional study in a nationally representative
      sample of 4672 women aged >=40 years using National Health and Nutrition
      Examination Survey (2003-2008). Individual food insecurity was assessed based on
      the U.S. Department of Agriculture 18-item validated household food security
      scale. Women were categorized as fully food secure (0 affirmative responses) or
      food insecure (1-10 affirmative responses). Obesity was defined as body mass
      index >=30 kg/m2. Outcomes were analyzed by multivariable logistic regression.
      RESULTS: Fourteen percent were food insecure. Women with food insecurity had 1.4
      the odds of obesity as those who were fully food secure, adjusting for
      race/ethnicity and health status (95% confidence interval [CI] 1.22-1.62). Food
      insecure women were 80% less likely to report strong social support than women
      who were fully food secure (95% CI 0.11-0.36). Social support as measured in this
      study did not modify the association between food insecurity and obesity.
      CONCLUSIONS: Women reporting food insecurity reported lower levels of social
      support and were more likely to experience obesity. Interventions to reduce
      obesity in women who are food insecure must consider the limited resources
      available to these women.

PMID- 29182495
TI  - Platelet Transfusion for Patients With Cancer: American Society of Clinical
      Oncology Clinical Practice Guideline Update.
AB  - Purpose To provide evidence-based guidance on the use of platelet transfusion in
      people with cancer. This guideline updates and replaces the previous ASCO
      platelet transfusion guideline published initially in 2001. Methods ASCO convened
      an Expert Panel and conducted a systematic review of the medical literature
      published from September 1, 2014, through October 26, 2016. This review builds on
      two 2015 systematic reviews that were conducted by the AABB and the International
      Collaboration for Transfusion Medicine Guidelines. For clinical questions that
      were not addressed by the AABB and the International Collaboration for
      Transfusion Medicine Guidelines (the use of leukoreduction and platelet
      transfusion in solid tumors or chronic, stable severe thrombocytopenia) or that
      were addressed partially (invasive procedures), the ASCO search extended back to
      January 2000. Results The updated ASCO review included 24 more recent
      publications: three clinical practice guidelines, eight systematic reviews, and
      13 observational studies. Recommendations The most substantial change to a
      previous recommendation involved platelet transfusion in the setting of
      hematopoietic stem-cell transplantation. Based on data from randomized controlled
      trials, adult patients who undergo autologous stem-cell transplantation at
      experienced centers may receive a platelet transfusion at the first sign of
      bleeding, rather than prophylactically. Prophylactic platelet transfusion at
      defined platelet count thresholds is still recommended for pediatric patients
      undergoing autologous stem-cell transplantation and for adult and pediatric
      patients undergoing allogeneic stem-cell transplantation. Other recommendations
      address platelet transfusion in patients with hematologic malignancies or solid
      tumors or in those who undergo invasive procedures. Guidance is also provided
      regarding the production of platelet products, prevention of Rh alloimmunization,
      and management of refractoriness to platelet transfusion (
      www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki ).

PMID- 29182496
TI  - Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced
      Cholangiocarcinoma.
AB  - Purpose No standard treatment exists for patients with cholangiocarcinoma for
      whom first-line gemcitabine-based therapy fails. Fibroblast growth factor
      receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of
      intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan
      FGFR kinase inhibitor, has shown preliminary clinical activity against tumors
      with FGFR alterations. Methods A multicenter, open-label, phase II study (
      ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity
      in patients age >= 18 years with advanced or metastatic cholangiocarcinoma
      containing FGFR2 fusions or other FGFR alterations whose disease had progressed
      while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21
      days, then 7 days off (28-day cycles). The primary end point was investigator
      assessed overall response rate. Results Sixty-one patients (35 women; median age,
      57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3)
      participated. At the prespecified data cutoff (June 30, 2016), 50 patients had
      discontinued treatment. All responsive tumors contained FGFR2 fusions. The
      overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate
      was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free
      survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included
      hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and
      alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25
      patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and
      palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class
      FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical
      activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2
      fusions. This promising antitumor activity supports continued development of
      BGJ398 in this highly selected patient population.

PMID- 29182497
TI  - Effect of Prophylactic Human Papillomavirus (HPV) Vaccination on Oral HPV
      Infections Among Young Adults in the United States.
AB  - Purpose The incidence of human papilloma virus (HPV)-positive oropharyngeal
      cancers has risen rapidly in recent decades among men in the United States. We
      investigated the US population-level effect of prophylactic HPV vaccination on
      the burden of oral HPV infection, the principal cause of HPV-positive
      oropharyngeal cancers. Methods We conducted a cross-sectional study of men and
      women 18 to 33 years of age (N = 2,627) within the National Health and Nutrition
      Examination Survey 2011 to 2014, a representative sample of the US population.
      Oral HPV infection with vaccine types 16, 18, 6, or 11 was compared by HPV
      vaccination status, as measured by self-reported receipt of at least one dose of
      the HPV vaccine. Analyses accounted for the complex sampling design and were
      adjusted for age, sex, and race. Statistical significance was assessed using a
      quasi-score test. Results Between 2011 and 2014, 18.3% of the US population 18 to
      33 years of age reported receipt of at least one dose of the HPV vaccine before
      the age of 26 years (29.2% in women and 6.9% in men; P < .001). The prevalence of
      oral HPV16/18/6/11 infections was significantly reduced in vaccinated versus
      unvaccinated individuals (0.11% v 1.61%; Padj = .008), corresponding to an
      estimated 88.2% (95% CI, 5.7% to 98.5%) reduction in prevalence after model
      adjustment for age, sex, and race. Notably, the prevalence of oral HPV16/18/6/11
      infections was significantly reduced in vaccinated versus unvaccinated men (0.0%
      v 2.13%; Padj = .007). Accounting for vaccine uptake, the population-level effect
      of HPV vaccination on the burden of oral HPV16/18/6/11 infections was 17.0%
      overall, 25.0% in women, and 6.9% in men. Conclusion HPV vaccination was
      associated with reduction in vaccine-type oral HPV prevalence among young US
      adults. However, because of low vaccine uptake, the population-level effect was
      modest overall and particularly low in men.

PMID- 29182498
TI  - Effect of Single-Session, Cryogen-Cooled Monopolar Radiofrequency Therapy on
      Sexual Function in Women with Vaginal Laxity: The VIVEVE I Trial.
AB  - OBJECTIVE: This subanalysis of the VIVEVE I trial aimed to evaluate the impact of
      cryogen-cooled monopolar radiofrequency (CMRF) therapy, for the treatment of
      vaginal laxity, on the domains of sexual function included in the Female Sexual
      Function Index (FSFI). MATERIALS AND METHODS: The VIVEVE I clinical trial was
      prospective, randomized, single-blind, and Sham-controlled. Nine clinical study
      centers in Canada, Italy, Spain, and Japan were included. This subanalysis
      included premenopausal women with self-reported vaginal laxity who had >=1 term
      vaginal delivery and a baseline FSFI total score <=26.5, indicating sexual
      dysfunction. Enrolled subjects were randomized (2:1) to receive CMRF therapy
      [Active (90 J/cm2) vs. Sham (<=1 J/cm2)] delivered to the vaginal tissue.
      Independent analyses were conducted for each FSFI domain to evaluate both the
      mean change, as well as the clinically important change for Active- versus Sham
      treated subjects at 6 months post-intervention. RESULTS: Subjects randomized to
      Active treatment (n = 73) had greater improvement than Sham subjects (n = 35) on
      all FSFI domains of sexual function at 6 months postintervention. The analysis of
      covariance change from baseline analyses showed statistically significant
      improvements, in favor of Active treatment, for sexual arousal (p = 0.004),
      lubrication (p = 0.04), and orgasm (p = 0.007). In addition, Active treatment was
      associated with clinically important and statistically significant improvements
      in sexual desire [Odds ratio (OR) = 3.01 (1.11-8.17)], arousal [OR = 2.73 (1.06
      7.04)], and orgasm [OR = 2.58 (1.08-6.18)]. CONCLUSIONS: This subanalysis showed
      CMRF therapy is associated with statistically significant and clinically
      important improvements in sexual function in women with vaginal laxity. These
      findings provide the first randomized, placebo-controlled energy-based device
      evidence for functional improvements associated with a nonsurgical modality for a
      highly prevalent and undertreated condition.

PMID- 29182499
TI  - Strategy to Identify and Test Putative Light-Sensitive Non-Opsin G-Protein
      Coupled Receptors: A Case Study.
AB  - The rise of high-throughput RNA sequencing (RNA-seq) and de novo transcriptome
      assembly has had a transformative impact on how we identify and study genes in
      the phototransduction cascade of non-model organisms. But the advantage provided
      by the nearly automated annotation of RNA-seq transcriptomes may at the same time
      hinder the possibility for gene discovery and the discovery of new gene
      functions. For example, standard functional annotation based on domain homology
      to known protein families can only confirm group membership, not identify the
      emergence of new biochemical function. In this study, we show the importance of
      developing a strategy that circumvents the limitations of semiautomated
      annotation and apply this workflow to photosensitivity as a means to discover non
      opsin photoreceptors. We hypothesize that non-opsin G-protein-coupled receptor
      (GPCR) proteins may have chromophore-binding lysines in locations that differ
      from opsin. Here, we provide the first case study describing non-opsin light
      sensitive GPCRs based on tissue-specific RNA-seq data of the common bay scallop
      Argopecten irradians (Lamarck, 1819). Using a combination of sequence analysis
      and three-dimensional protein modeling, we identified two candidate proteins. We
      tested their photochemical properties and provide evidence showing that these two
      proteins incorporate 11-cis and/or all-trans retinal and react to light
      photochemically. Based on this case study, we demonstrate that there is potential
      for the discovery of new light-sensitive GPCRs, and we have developed a workflow
      that starts from RNA-seq assemblies to the discovery of new non-opsin, GPCR-based
      photopigments.

PMID- 29182500
TI  - New Insights from Genetic Data Sets on the Function and Evolution of Visual
      Systems: Introduction to a Virtual Symposium in The Biological Bulletin.

PMID- 29182501
TI  - Radiolar Eyes of Serpulid Worms (Annelida, Serpulidae): Structures, Function, and
      Phototransduction.
AB  - Fan worms, represented by sabellid and serpulid polychaetes, have an astonishing
      array of unusual eyes and photoreceptors located on their eponymous feeding
      appendages. Here we organize the previous descriptions of these eyes in serpulids
      and report new anatomical, molecular, and physiological data regarding their
      structure, function, and evolution and the likely identity of their
      phototransduction machinery. We report that, as in sabellids, serpulids display a
      broad diversity of radiolar eye arrangements and ocellar structures. Furthermore,
      the visual pigment expressed in the eyes of Spirobranchus corniculatus, a species
      of the charismatic Christmas tree worms, absorbs light maximally at 464 nm in
      wavelength. This visual pigment closely matches the spectrum of downwelling
      irradiance in shallow coral reef habitats and lends support to the hypothesis
      that these radiolar photoreceptors function as a silhouette-detecting "burglar
      alarm" that triggers a rapid withdrawal response when the worm is threatened by
      potential predators. Finally, we report on the transcriptomic sequencing results
      for the radiolar eyes of S. corniculatus, which express invertebrate c-type
      opsins in their ciliary radiolar photoreceptors, closely related to the opsin
      found in the radiolar eyes of the sabellid Acromegalomma interruptum. We explore
      the potential for a shared evolutionary lineage between the radiolar
      photoreceptors of serpulids and sabellids and consider these unique innovations
      in the broader context of metazoan eye evolution.

PMID- 29182502
TI  - Expression of G Proteins in the Eyes and Parietovisceral Ganglion of the Bay
      Scallop Argopecten irradians.
AB  - A multitude of image-forming eyes are spread across the bodies of certain
      invertebrates. Recent efforts have characterized how these eyes function, but
      less progress has been made toward describing the neural structures associated
      with them. Scallops, for example, have a distributed visual system that includes
      dozens of eyes whose optic nerves project to the lateral lobes of the
      parietovisceral ganglion (PVG). To identify sensory receptors and chemical
      synapses associated with the scallop visual system, we studied the expression of
      four G protein alpha subunits (Galphai, Galphao, Galphaq, and Galphas) in the
      eyes and PVG of the bay scallop Argopecten irradians (Lamarck, 1819). In the eyes
      of A. irradians, we noted expression of Galphao by the ciliary photoreceptors of
      the distal retina, expression of Galphaq by the rhabdomeric photoreceptors of the
      proximal retina, and the expression of Galphao and Galphaq by the cells of the
      cornea; we did not, however, detect expression of Galphai or Galphas in the eyes.
      In the PVG of A. irradians, we noted widespread expression of Galphai, Galphao,
      and Galphaq. The expression of Galphas was limited to fine neurites in the
      lateral and ventral central lobes, as well as large unipolar neurons in the
      dorsal central lobes. Our findings suggest that light detection by the eyes of A.
      irradians is conferred primarily by photoreceptors that express Galphao or
      Galphaq, that the corneal cells of scallops may contain sensory receptors and/or
      receive neural input, and that G protein labeling is useful for visualizing
      substructures and identifying specific populations of cells within the nervous
      systems of invertebrates.

PMID- 29182503
TI  - Molecular Evolution of Spider Vision: New Opportunities, Familiar Players.
AB  - Spiders are among the world's most species-rich animal lineages, and their visual
      systems are likewise highly diverse. These modular visual systems, composed of
      four pairs of image-forming "camera" eyes, have taken on a huge variety of forms,
      exhibiting variation in eye size, eye placement, image resolution, and field of
      view, as well as sensitivity to color, polarization, light levels, and motion
      cues. However, despite this conspicuous diversity, our understanding of the
      genetic underpinnings of these visual systems remains shallow. Here, we review
      the current literature, analyze publicly available transcriptomic data, and
      discuss hypotheses about the origins and development of spider eyes. Our efforts
      highlight that there are many new things to discover from spider eyes, and yet
      these opportunities are set against a backdrop of deep homology with other
      arthropod lineages. For example, many (but not all) of the genes that appear
      important for early eye development in spiders are familiar players known from
      the developmental networks of other model systems (e.g., Drosophila). Similarly,
      our analyses of opsins and related phototransduction genes suggest that spider
      photoreceptors employ many of the same genes and molecular mechanisms known from
      other arthropods, with a hypothesized ancestral spider set of four visual and
      four nonvisual opsins. This deep homology provides a number of useful footholds
      into new work on spider vision and the molecular basis of its extant variety. We
      therefore discuss what some of these first steps might be in the hopes of
      convincing others to join us in studying the vision of these fascinating
      creatures.

PMID- 29182504
TI  - Molecular Characterization of Copepod Photoreception.
AB  - Copepod crustaceans are an abundant and ecologically significant group whose
      basic biology is guided by numerous visually guided behaviors. These behaviors
      are driven by copepod eyes, including naupliar eyes and Gicklhorn's organs, which
      vary widely in structure and function among species. Yet little is known about
      the molecular aspects of copepod vision. In this study we present a general
      overview of the molecular aspects of copepod vision by identifying
      phototransduction genes from newly generated and publicly available RNA
      sequencing data and assemblies from 12 taxonomically diverse copepod species. We
      identify a set of 10 expressed transcripts that serve as a set of target genes
      for future studies of copepod phototransduction. Our more detailed evolutionary
      analyses of the opsin gene responsible for forming visual pigments found that all
      of the copepod species investigated express two main groups of opsins: middle
      wavelength-sensitive (MWS) opsins and pteropsins. Additionally, there is evidence
      from a few species (e.g., Calanus finmarchicus, Eurytemora affinis, Paracyclopina
      nana, and Lernaea cyprinacea) for the expression of two additional groups of
      opsins-the peropsins and rhodopsin 7 (Rh7) opsins-at low levels or distinct
      developmental stages. An ontogenetic analysis of opsin expression in Calanus
      finmarchicus found the expression of a single dominant MWS opsin, as well as
      evidence for differences in expression across development in some MWS, pteropsin,
      and Rh7 opsins, with expression peaking in early naupliar through early
      copepodite stages.

PMID- 29182505
TI  - Opsin Expression in the Central Nervous System of the Mantis Shrimp
      Neogonodactylus oerstedii.
AB  - Visual pigments, each composed of an opsin protein covalently bound to a
      chromophore molecule, confer light sensitivity for vision. The eyes of some
      species of stomatopod crustaceans, or mantis shrimp, can express dozens of
      different opsin genes. The opsin diversity, along with spectral filters and
      unique tripartite eye structure, bestow upon stomatopods unusually complex visual
      systems. Although opsins are found in tissues outside typical image-forming eyes
      in other animals, extraocular opsin expression in stomatopods, animals well known
      for their diversity of opsins, was unknown. Caudal photoreception in the central
      nervous system of decapod crustaceans, a group closely related to stomatopod
      crustaceans, is thought to be opsin based. However, electrophysiological data
      suggest that stomatopods do not have caudal photoreceptors. In this study, we
      identified mRNAs that could encode four different opsins and several components
      of a potential Gq-mediated phototransduction pathway in the central nervous
      system of the Caribbean mantis shrimp Neogonodactylus oerstedii. The four opsins
      are abundantly expressed in the cerebral ganglion, or brain, with little or no
      expression in the remainder of the ventral nerve cord. Our data suggest that
      there are previously undiscovered cerebral photoreceptors in stomatopods.

PMID- 29182506
TI  - Opsins and Their Expression Patterns in the Xiphosuran Limulus polyphemus.
AB  - The American horseshoe crab Limulus polyphemus (Linnaeus, 1758) is one of four
      extant species of xiphosuran chelicerates, the sister group to arachnids. Because
      of their position in the arthropod family tree and because they exhibit many
      plesiomorphic characteristics, Xiphosura are considered a proxy for the
      euchelicerate ancestor and therefore important for understanding the evolution
      and diversification of chelicerates and arthropods. Limulus polyphemus is the
      most extensively studied xiphosuran, and its visual system has long been a focus
      of studies critical for our understanding of basic mechanisms of vision and the
      evolution of visual systems in arthropods. Building upon a wealth of information
      about the anatomy and physiology of its visual system, advances in genetic
      approaches have greatly expanded possibilities for understanding its
      biochemistry. This review focuses on studies of opsin expression in L.
      polyphemus, which have been significantly advanced by the availability of
      transcriptomes and a recent high-quality assembly of its genome. These studies
      show that the repertoire of expressed opsins in L. polyphemus is far larger than
      anticipated, that the regulation of their expression in rhabdoms is far more
      complex than anticipated, and that photosensitivity may be distributed widely
      throughout the L. polyphemus central nervous system. The visual system of L.
      polyphemus is now arguably the best understood among chelicerates, and as such,
      it is a critical resource for furthering our understanding of the evolution and
      diversification of visual systems in arthropods.

PMID- 29182507
TI  - Implant Dentistry: The American Board of Dental Specialties Provides a Better Way
      for Specialty Recognition.

PMID- 29182508
TI  - Ethnic disparities in the dietary requirement for vitamin D during pregnancy:
      considerations for nutrition policy and research.
AB  - Despite the inverse association between skin colour and efficiency of cutaneous
      vitamin D synthesis, in addition to the widely accepted racial disparity in
      vitamin D status, populations of ethnic minority are understudied in terms of
      setting target serum 25-hydroxyvitamin D concentrations and corresponding dietary
      requirements for vitamin D. In minority groups, prevention of vitamin D
      deficiency on a population basis is challenging due to the lack of clarity
      surrounding the metabolism and transport of vitamin D. Authoritative agencies
      have been unable to define pregnancy-specific dietary recommendations for vitamin
      D, owing to an absence of sufficient evidence to confirm whether nutritional
      requirements for vitamin D are altered during pregnancy. While the question of
      setting race- and pregnancy-specific dietary reference values for vitamin D has
      not been addressed to date, endemic vitamin D deficiency has been reported among
      gravidae worldwide, specifically among ethnic minorities and white women resident
      at high latitude. In light of the increased risk of nutritional rickets among
      infants of ethnic minority, coupled with growing evidence for potential non
      skeletal roles of vitamin D in perinatal health, determination of the dietary
      vitamin D requirement that will prevent deficiency during pregnancy is a research
      priority. However, systematic approaches to establishing dietary requirements are
      limited by the quality of the available evidence and the under-representation of
      minority groups in clinical research. This review considers the evidence for
      racial differences in vitamin D status and response to vitamin D supplementation,
      with particular application to pregnancy-specific requirements among ethnic
      minorities resident at high latitudes.

PMID- 29182509
TI  - The 3C protease of enterovirus A71 counteracts the activity of host zinc-finger
      antiviral protein (ZAP).
AB  - Enterovirus A71 (EV-A71) is a positive-strand RNA virus that causes hand-foot
      mouth disease and neurological complications in children and infants. Although
      the underlying mechanisms remain to be further defined, impaired immunity is
      thought to play an important role. The host zinc-finger antiviral protein (ZAP),
      an IFN-stimulated gene product, has been reported to specifically inhibit the
      replication of certain viruses. However, whether ZAP restricts the infection of
      enteroviruses remains unknown. Here, we report that EV-A71 infection upregulates
      ZAP mRNA in RD and HeLa cells. Moreover, ZAP overexpression rendered 293 T cells
      resistant to EV-A71 infection, whereas siRNA-mediated depletion of endogenous ZAP
      enhanced EV-A71 infection. The EV-A71 infection stimulated site-specific
      proteolysis of two ZAP isoforms, leading to the accumulation of a 40 kDa N
      terminal ZAP fragment in virus-infected cells. We further revealed that the 3C
      protease (3Cpro) of EV-A71 mediates ZAP cleavage, which requires protease
      activity. Furthermore, ZAP variants with single amino acid substitutions at Gln
      369 were resistant to 3Cpro cleavage, implying that Gln-369 is the sole cleavage
      site in ZAP. Moreover, although ZAP overexpression inhibited EV-A71 replication,
      the cleaved fragments did not show this effect. Our results indicate that an
      equilibrium between ZAP and enterovirus 3Cpro controls viral infection. The
      findings in this study suggest that viral 3Cpro mediated ZAP cleavage may
      represent a mechanism to escape host antiviral responses.

PMID- 29182510
TI  - High dengue virus load differentially modulates human microvascular endothelial
      barrier function during early infection.
AB  - Plasma leakage is the main pathophysiological feature in severe dengue, resulting
      from altered vascular barrier function associated with an inappropriate immune
      response triggered upon infection. The present study investigated functional
      changes using an electric cell-substrate impedance sensing system in four (brain,
      dermal, pulmonary and retinal) human microvascular endothelial cell (MEC) lines
      infected with purified dengue virus, followed by assessment of cytokine profiles
      and the expression of inter-endothelial junctional proteins. Modelling of changes
      in electrical impedance suggests that vascular leakage in dengue-infected MECs is
      mostly due to the modulation of cell-to-cell interactions, while this loss of
      vascular barrier function observed in the infected MECs varied between cell lines
      and DENV serotypes. High levels of inflammatory cytokines (IL-6 and TNF-alpha),
      chemokines (CXCL1, CXCL5, CXCL11, CX3CL1, CCL2 and CCL20) and adhesion molecules
      (VCAM-1) were differentially produced in the four infected MECs. Further, the
      tight junctional protein, ZO-1, was down-regulated in both the DENV-1-infected
      brain and pulmonary MECs, while claudin-1, PECAM-1 and VE-cadherin were
      differentially expressed in these two MECs after infection. Non-purified virus
      stock was also studied to investigate the impact of virus stock purity on dengue
      specific immune responses, and the results suggest that virus stock propagated
      through cell culture may include factors that mask or alter the DENV-specific
      immune responses of the MECs. The findings of the present study show that high
      DENV load differentially modulates human microvascular endothelial barrier
      function and disrupts the function of inter-endothelial junctional proteins
      during early infection with organ-specific cytokine production.

PMID- 29182511
TI  - Molecular cloning and overexpression of DGA1, an acyl-CoA-dependent
      diacylglycerol acyltransferase, in the oleaginous yeast Rhodosporidiobolus
      fluvialis DMKU-RK253.
AB  - Triacylglycerol (TAG) is a major component of lipid storage in yeast. The acyl
      CoA: diacylgycerol acyltransferase (DGAT) that catalyzes the final and rate
      limiting step in the production of TAG is rather interesting. Consequently,
      cloning and analysis of the gene-encoding TAG synthase, diacylglycerol
      acyltransferase gene (DGA1), of the oleaginous yeast Rhodosporidiobolus fluvialis
      DMKU-RK253 were undertaken. Analysis of the deduced amino acid sequence of DGA1
      from R. fluvialis DMKU-RK253 (RfDGA1) showed similarity with the acyl
      CoA:diacylglycerol acyltransferase 2 (DGAT2) from other organisms. The cDNA of
      RfDGA1 was cloned into the yeast expression vector pYES2 and heterologously
      overexpressed in Saccharomyces cerevisiae. One of the transformants showed a 1.6
      fold increase in lipid content compared with the wild-type strain harbouring the
      pYES2 empty vector. Furthermore, DGA1 overexpression in R. fluvialis DMKU-RK253
      resulted in a 2.5-fold increase in lipid content when compared with the wild-type
      strain, and no significant differences in fatty acid composition were observed
      between RfDGA1-overexpressed and wild-type strains. Taken together, our results
      supported our hypothesis that the RfDGA1 is a genetic factor that can be used for
      the development of a strain with improved lipid accumulation capabilities.

PMID- 29182513
TI  - Both hypothyroidism and hyperthyroidism increase plasma irisin levels in rats.
AB  - Background A recently discovered hormone, irisin is accepted to be significantly
      involved in the regulation of body weight. Thyroid functions may be, directly or
      indirectly, associated with irisin. Aim The aim of the present study is to
      determine the effect of experimental thyroid dysfunction on irisin levels in
      rats. Methods The study registered 40 adult male Sprague-Dawley rats, which were
      allocated to groups as follows: 1. Control; 2. Hypothyroidism induced by
      injection of 10 mg/kg/day intraperitoneal propylthiouracil (PTU) for 3 weeks; 3.
      Hypothyroidism (PTU 2 weeks) + L-thyroxin (1.5 mg/kg/day for 1 week); 4.
      Hyperthyroidism induced in rats by 3-week thyroxin (0.3 mg/kg/day); 5.
      Hyperthyroidism + PTU. At the end of the study, blood samples were collected to
      quantify free triiodothyronine (FT3), free triiodothyronine (FT4) and irisin
      levels. Results FT3 and FT4 levels were reduced in hypothyroidism and were
      significantly elevated in hyperthyroidism (p < 0.001). Irisin values, on the
      other hand, were found to be elevated in both hypothyroidism and hyperthyroidism
      groups (p < 0.001). Conclusion The results of the study suggest that irisin
      values increase in thyroid dysfunction, hypo- and hyperthyroidism, and that when
      hypothyroidism is corrected by thyroxin administration and hyperthyroidism by PTU
      injection, plasma irisin values go back to normal.

PMID- 29182512
TI  - Global mapping of MtrA-binding sites links MtrA to regulation of its targets in
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis employs two-component systems (TCSs) for survival
      within its host. The TCS MtrAB is conserved among mycobacteria. The response
      regulator MtrA is essential in M. tuberculosis. The genome-wide chromatin
      immunoprecipitation (ChIP) sequencing performed in this study suggested that MtrA
      binds upstream of at least 45 genes of M. tuberculosis, including those involved
      in cell wall remodelling, stress responses, persistence and regulation of
      transcription. It binds to the promoter regions and regulates the peptidoglycan
      hydrolases rpfA and rpfC, which are required for resuscitation from dormancy. It
      also regulates the expression of whiB4, a critical regulator of the oxidative
      stress response, and relF, one-half of the toxin-antitoxin locus relFG. We have
      identified a new consensus 9 bp loose motif for MtrA binding. Mutational changes
      in the consensus sequence greatly reduced the binding of MtrA to its newly
      identified targets. Importantly, we observed that overexpression of a gain-of
      function mutant, MtrAY102C, enhanced expression of the aforesaid genes in M.
      tuberculosis isolated from macrophages, whereas expression of each of these
      targets was lower in M. tuberculosis overexpressing a phosphorylation-defective
      mutant, MtrAD56N. This result suggests that phosphorylated MtrA (MtrA-P) is
      required for the expression of its targets in macrophages. Our data have
      uncovered new MtrA targets that suggest that MtrA is required for a
      transcriptional response that likely enables M. tuberculosis to persist within
      its host and emerge out of dormancy when the conditions are favourable.

PMID- 29182514
TI  - Respect for professors: an often underappreciated component of professionalism in
      medical education.

PMID- 29182515
TI  - Sesquiterpenes from the Saudi Red Sea: Litophyton arboreum with their cytotoxic
      and antimicrobial activities.
AB  - A new pseudoguaiane-type sesquiterpene named litopharbol (1) was isolated from
      the methanolic extract of the Red Sea soft coral Litophyton arboreum, along with
      known sesquiterpenoids alismol (2), alismorientol B (3), teuhetenone A (4), and
      calamusin I (5); steroid, 24-methyl-cholesta-5,24(28)-diene-3beta-ol (6), alkyl
      glyceryl ether, chimyl alcohol (7); sphingolipid, erythro-N-dodecanoyl
      docosasphinga-(4E,8E)-dienine (8); and nitrogenous bases, thymine (9) and
      thymidine (10). The structures were determined on the basis of nuclear magnetic
      resonance (NMR) spectroscopic (1D and 2D NMR data including heteronuclear single
      quantum coherence spectroscopy, heteronuclear multiple-bond correlation
      spectroscopy, and nuclear Overhauser effect spectroscopy) and mass spectrometric
      analyses. Compounds 1-5 were explored for antimicrobial activity and cancer cell
      line sensitivity tests. Compound 1 exhibited antibacterial activity against
      Bacillus cereus with a minimum inhibition concentration of 1.8 MUg/mL, whereas
      compound 3 showed significant potent cytotoxic effect against MCF-7 (breast
      cancer cells) with IC50 4.32 MUM.

PMID- 29182516
TI  - ProteinAC: a frequency domain technique for analyzing protein dynamics.
AB  - It is widely believed that the interactions of proteins with ligands and other
      proteins are determined by their dynamic characteristics as opposed to only
      static, time-invariant processes. We propose a novel computational technique,
      called ProteinAC (PAC), that can be used to analyze small scale functional
      protein motions as well as interactions with ligands directly in the frequency
      domain. PAC was inspired by a frequency domain analysis technique that is widely
      used in electronic circuit design, and can be applied to both coarse-grained and
      all-atom models. It can be considered as a generalization of previously proposed
      static perturbation-response methods, where the frequency of the perturbation
      becomes the key. We discuss the precise relationship of PAC to static
      perturbation-response schemes. We show that the frequency of the perturbation may
      be an important factor in protein dynamics. Perturbations at different
      frequencies may result in completely different response behavior while magnitude
      and direction are kept constant. Furthermore, we introduce several novel
      frequency dependent metrics that can be computed via PAC in order to characterize
      response behavior. We present results for the ferric binding protein that
      demonstrate the potential utility of the proposed techniques.

PMID- 29182517
TI  - The electronic and optical properties of the sulvanite compounds: a many-body
      perturbation and time-dependent density functional theory study.
AB  - We have studied, by means of first-principles calculations, the electronic and
      optical properties of the sulvanite family: Cu3MX4 (M  =  V, Nb, Ta and X  =  S,
      Se), which, due to its broad range of gaps and chemical stability, have emerged
      as promising materials for technological applications such as photovoltaics and
      transparent conductivity. To address the reliability of those properties we have
      used semi-local and hybrid functionals (PBEsol, HSE06), many-body perturbation
      theory (G0W0 approximation and Bethe-Salpeter equation), and time-dependent
      density functional theory (revised bootstrap kernel) to calculate the quasi
      particle dispersion relation, band gaps, the imaginary part of the macroscopic
      dielectric function and the absorption coefficient. The calculated valence band
      maximum and the conduction band minimum are located at the R and X-points,
      respectively. The calculated gaps using PBEsol are between 0.81 and 1.88 eV, with
      HSE06 into 1.73 and 2.94 eV, whereas the G0W0 values fall into the 1.91-3.19 eV
      range. The calculated dielectric functions and absorption coefficients show that
      all these compounds present continuous excitonic features when the Bethe-Salpeter
      equation is used. Contrarily, the revised bootstrap kernel is incapable of
      describing the excitonic spectra. The calculated optical spectra show that Cu3VS4
      and Cu3MSe4 have good absorption in the visible, whereas Cu3NbS4 and Cu3TaS4 have
      it on the near ultraviolet.

PMID- 29182518
TI  - Temperature-dependence of the single-cell variability in the kinetics of
      transcription activation in Escherichia coli.
AB  - From in vivo single-cell, single-RNA measurements of the activation times and
      subsequent steady-state active transcription kinetics of a single-copy Lac-ara-1
      promoter in Escherichia coli, we characterize the intake kinetics of the inducer
      (IPTG) from the media, following temperature shifts. For this, for temperature
      shifts of various degrees, we obtain the distributions of transcription
      activation times as well as the distributions of intervals between consecutive
      RNA productions following activation in individual cells. We then propose a novel
      methodology that makes use of deconvolution techniques to extract the mean and
      the variability of the distribution of intake times. We find that cells,
      following shifts to low temperatures, have higher intake times, although, counter
      intuitively, the cell-to-cell variability of these times is lower. We validate
      the results using a new methodology for direct estimation of mean intake times
      from measurements of activation times at various inducer concentrations. The
      results confirm that E. coli's inducer intake times from the environment are
      significantly higher following a shift to a sub-optimal temperature. Finally, we
      provide evidence that this is likely due to the emergence of additional rate
      limiting steps in the intake process at low temperatures, explaining the reduced
      cell-to-cell variability in intake times.

PMID- 29182519
TI  - Elastic moduli of a Brownian colloidal glass former.
AB  - The static, dynamic and flow-dependent shear moduli of a binary mixture of
      Brownian hard disks are studied by an event-driven molecular dynamics simulation.
      Thereby, the emergence of rigidity close to the glass transition encoded in the
      static shear modulus [Formula: see text] is accessed by three methods. Results
      from shear stress auto-correlation functions, elastic dispersion relations, and
      the elastic response to strain deformations upon the start-up of shear flow are
      compared. This enables one to sample the time-dependent shear modulus [Formula:
      see text] consistently over several decades in time. By that a very precise
      specification of the glass transition point and of [Formula: see text] is
      feasible. Predictions by mode coupling theory of a finite shear modulus at the
      glass transition, of alpha-scaling in fluid states close to the transition, and
      of shear induced decay in yielding glass states are tested and broadly verified.

PMID- 29182520
TI  - Corrigendum: Angle-resolved photoemission spectroscopy studies of metallic
      surface and interface states of oxide insulators (J. Phys.: Condens. Matter 29
      (2017) 433005).
AB  - The citation given in reference [98] is incorrect. It should be Berner <i>et
      al</i> 2010 <i>Phys. Rev. Lett.</i> <b>110</b> 247601.

PMID- 29182521
TI  - Extraction and physicochemical characterization of chitin and chitosan isolated
      from house cricket.
AB  - Chitin ranks next to cellulose as the most important bio-polysaccharide which can
      primarily be extracted from crustacean shells. However, the emergence of new
      areas of the application of chitin and its derivatives are on the increase and
      there is growing demand for new chitin sources. In this study, therefore, an
      attempt was made to extract chitin from the house cricket (Brachytrupes
      portentosus) by a chemical method. The physicochemical properties of chitin and
      chitosan extracted from crickets were compared with commercial chitin and
      chitosan extracted from shrimps, in terms of proximate analysis in particular, of
      their ash and moisture content. Also, infrared spectroscopy, x-ray diffraction
      (XRD), scanning electron microscopy and elemental analysis were conducted. The
      chitin and chitosan yield of the house cricket ranges over 4.3%-7.1% and 2.4%
      5.8% respectively. Chitin and chitosan from crickets compares favourably with
      those extracted from shrimps, and were found to exhibit some similarities. The
      result shows that cricket and shrimp chitin and chitosan have the same degree of
      acetylation and degree of deacetylation of 108.1% and 80.5% respectively,
      following Fourier transform infrared spectroscopy. The characteristic XRD
      strong/sharp peaks of 9.4 and 19.4 degrees  for alpha-chitin are common for both
      cricket and shrimp chitin. The percentage ash content of chitin and chitosan
      extracted from B. portentosus is 1%, which is lower than that obtained from
      shrimp products. Therefore, cricket chitin and chitosan can be said to be of
      better quality and of purer form than commercially produced chitin and chitosan
      from shrimp. Based on the quality of the product, chitin and chitosan isolated
      from B. portentosus can replace commercial chitin and chitosan in terms of
      utilization and applications. Therefore, B. portentosus is a promising
      alternative source of chitin and chitosan.

PMID- 29182522
TI  - Varieties of charge distributions in coat proteins of ssRNA+  viruses.
AB  - A major part of the interactions involved in the assembly and stability of
      icosahedral, positive-sense single-stranded RNA (ssRNA+) viruses is electrostatic
      in nature, as can be inferred from the strong pH- and salt-dependence of their
      assembly phase diagrams. Electrostatic interactions do not act only between the
      capsid coat proteins (CPs), but just as often provide a significant contribution
      to the interactions of the CPs with the genomic RNA, mediated to a large extent
      by positively charged, flexible N-terminal tails of the CPs. In this work, we
      provide two clear and complementary definitions of an N-terminal tail of a
      protein, and use them to extract the tail sequences of a large number of CPs of
      ssRNA+  viruses. We examine the pH-dependent interplay of charge on both tails
      and CPs alike, and show that-in contrast to the charge on the CPs-the net
      positive charge on the N-tails persists even to very basic pH values. In
      addition, we note a limit to the length of the wild-type genomes of those viruses
      which utilize positively charged tails, when compared to viruses without charged
      tails and similar capsid size. At the same time, we observe no clear connection
      between the charge on the N-tails and the genome lengths of the viruses included
      in our study.

PMID- 29182523
TI  - Graphene oxide reduction by solid-state laser irradiation for bolometric
      applications.
AB  - We present a method for reduced graphene oxide (GO) patterning on the surface of
      GO film by a 445 nm solid-state laser with the adjustable fluence from 0.2-20 kJ
      cm-2. We demonstrate that the optimal argon concentration in air to obtain good
      quality reduced GO films is 90%. Varying the laser irradiation energy density
      allows controlling the resistance and I G /I D and I G /I 2D ratios of Raman peak
      intensities. As a result, we demonstrate the possibility of forming of conductive
      patterns with a sheet resistance of 189 Ohm/? and ~1 MUm film thickness by a
      local reduction of the GO. The fabricated structures reveal excellent bolometric
      response with a high speed and sensitivity to the radiation in the visible
      wavelength region.

PMID- 29182524
TI  - Long-term proton pump inhibitor therapy leads to small bowel bacterial overgrowth
      as determined by breath hydrogen and methane excretion.
AB  - OBJECTIVES: Prolonged suppression of gastric acid secretion by proton pump
      inhibitors (PPIs) may alter the bacterial microbiota of the upper
      gastrointestinal tract and lead to small bowel bacterial overgrowth (SBBO).
      Published reports have shown conflicting results on the association between PPI
      therapy and risk of SBBO development. We evaluated whether long-term PPI
      treatment is associated with presence of SBBO as determined by breath hydrogen
      (H2) and methane (CH4) excretion. We also assessed the differences in H2/CH4
      excretion patterns in patients taking PPI compared with those not taking the
      medication and searched for the potential predictors of a positive breath test
      result. MATERIAL AND METHODS: This was a prospective cohort study that included
      67 PPI-treated patients (PPIT) and 62 not-receiving PPI (C, comparison). PPIT and
      C underwent a glucose H2/CH4 breath test (HMBT) to determine the presence of
      SBBO. RESULTS: The prevalence of SBBO was significantly higher in PPIT compared
      to C (44.8% versus 21%, p = 0.005, OR = 3.06, 95% CI 1.40-6.66) as determined by
      H2 and CH4 excretion. We found that PPIT had all H2 test parameters (baseline H2
      levels, maximum peak of H2 as well as mean H2 through the whole test)
      significantly higher than C. Even those PPIT who did not meet the criteria of
      breath test positivity had statistically higher breath H2 levels compared to C.
      Although we did not observe significant differences in CH4 excretion between
      groups, 19.4% of PPIT and 12.9% of C would have had a false-negative HMBT results
      had CH4 not been taken into account. CONCLUSIONS: Long-term PPI use was found to
      be significantly associated with SBBO development as determined by breath H2 and
      CH4 excretion. CH4 determination reduces the number of falsely negative test
      results.

PMID- 29182525
TI  - Climatic Factors and Influenza Transmission, Spain, 2010-2015.
AB  - The spatio-temporal distribution of influenza is linked to variations in
      meteorological factors, like temperature, absolute humidity, or the amount of
      rainfall. The aim of this study was to analyse the association between influenza
      activity, and meteorological variables in Spain, across five influenza seasons:
      2010-2011 through to 2014-2015 using generalized linear negative binomial mixed
      models that we calculated the weekly influenza proxies, defined as the weekly
      influenza-like illness rates, multiplied by the weekly proportion of respiratory
      specimens that tested positive for influenza. The results showed an association
      between influenza transmission and dew point and cumulative precipitation. In
      increase in the dew point temperature of 5 degrees produces a 7% decrease in the
      Weekly Influenza Proxy (RR 0.928, IC: 0.891-0.966), and while an increase of 10
      mm in weekly rainfall equates to a 17% increase in the Weekly Influenza Proxy (RR
      1.172, IC: 1.097-1.251). Influenza transmission in Spain is influenced by
      variations in meteorological variables as temperature, absolute humidity, or the
      amount of rainfall.

PMID- 29182526
TI  - Immunohistochemical Analysis of Rat Renal Tumours Caused by Ochratoxin A.
AB  - Experimental renal cancer caused by ochratoxin A (OTA) in rats was first defined
      in the US National Toxicology Program (1989) and raised questions about any
      aetiological role in human urinary tract tumours. A review of histopathology in
      several rat kidney tumours from dietary OTA in recently described London studies,
      augmented by clinical immunohistochemistry for the first time for this mycotoxin,
      establishes their renal tubular cell origin. It had been assumed that the toxin
      might cause the human urothelial tumours associated with Balkan endemic
      nephropathy, but the present study could not support this. Comparison with a
      similar review of a metastasising renal tumour from a female rat of the NTP study
      consistently shows the kidney as the primary carcinogenic site for OTA.
      Morphological heterogeneity of these kidney tumours as epithelioid and/or
      sarcomatoid is revealed. Leiomyosarcoma was also diagnosed, and rhabdomyosarcoma
      differentiation was observed in the exceptionally aggressive NTP female tumour.
      The present pilot study involving immunohistochemistry indicates need for wider
      review of archived tumours for experimental evidence before formulating any
      epidemiological basis from a rat model for OTA's relevance to idiopathic human
      renal cell carcinoma. Although the NTP study concluded that females are less
      sensitive to OTA than males, some female tumours still had heterogeneous
      morphology.

PMID- 29182527
TI  - All-Fiber Laser Curvature Sensor Using an In-Fiber Modal Interferometer Based on
      a Double Clad Fiber and a Multimode Fiber Structure.
AB  - An all-fiber curvature laser sensor by using a novel modal interference in-fiber
      structure is proposed and experimentally demonstrated. The in-fiber device,
      fabricated by fusion splicing of multimode fiber and double-clad fiber segments,
      is used as wavelength filter as well as the sensing element. By including a
      multimode fiber in an ordinary modal interference structure based on a double
      clad fiber, the fringe visibility of the filter transmission spectrum is
      significantly increased. By using the modal interferometer as a curvature
      sensitive wavelength filter within a ring cavity erbium-doped fiber laser, the
      spectral quality factor Q is considerably increased. The results demonstrate the
      reliability of the proposed curvature laser sensor with advantages of robustness,
      ease of fabrication, low cost, repeatability on the fabrication process and
      simple operation.

PMID- 29182528
TI  - Circular RNAs (circRNAs) in Health and Disease.
AB  - Splicing events do not always produce a linear transcript. Circular RNAs
      (circRNAs) are a class of RNA that are emerging as key new members of the gene
      regulatory milieu, which are produced by back-splicing events within genes. In
      circRNA formation, rather than being spliced in a linear fashion, exons can be
      circularised by use of the 3' acceptor splice site of an upstream exon, leading
      to the formation of a circular RNA species. circRNAs have been demonstrated
      across species and have the potential to present genetic information in new
      orientations distinct from their parent transcript. The importance of these RNA
      players in gene regulation and normal cellular homeostasis is now beginning to be
      recognised. They have several potential modes of action, from serving as sponges
      for micro RNAs and RNA binding proteins, to acting as transcriptional regulators.
      In accordance with an important role in the normal biology of the cell,
      perturbations of circRNA expression are now being reported in association with
      disease. Furthermore, the inherent stability of circRNAs conferred by their
      circular structure and exonuclease resistance, and their expression in blood and
      other peripheral tissues in association with endosomes and microvesicles, renders
      them excellent candidates as disease biomarkers. In this review, we explore the
      state of knowledge on this exciting class of transcripts in regulating gene
      expression and discuss their emerging role in health and disease.

PMID- 29182529
TI  - Placing Salt/Soy Sauce at Dining Tables and Out-Of-Home Behavior Are Related to
      Urinary Sodium Excretion in Japanese Secondary School Students.
AB  - We investigated whether home environment, salt knowledge, and salt-use behavior
      were associated with urinary sodium (Na) excretion in Japanese secondary school
      students. Students (267; mean age, 14.2 years) from Suo-Oshima, Japan, collected
      three overnight urine samples and completed a salt environment/knowledge/behavior
      questionnaire. A subset of students (n = 66) collected, on non-consecutive days,
      two 24 h urine samples, and this subset was used to derive a formula for
      estimating 24 h Na excretion. Generalized linear models were used to examine the
      association between salt environment/knowledge/behavior and Na excretions.
      Students that had salt or soy sauce placed on the dining table during meals
      excreted more Na than those that did not (pfor trend < 0.05). A number of foods
      to which the students added seasonings were positively associated with Na
      excretion (pfor trend = 0.005). The students who frequently bought foods at
      convenience stores or visited restaurants excreted more Na in urine than those
      who seldom bought foods (pfor trend < 0.05). Knowledge about salt or
      discretionary seasoning use was not significantly associated with Na excretion.
      The associations found in this study indicate that home environment and salt-use
      behavior may be a target for a public health intervention to reduce salt intake
      of secondary school students.

PMID- 29182530
TI  - Nodule-Enriched GRETCHEN HAGEN 3 Enzymes Have Distinct Substrate Specificities
      and Are Important for Proper Soybean Nodule Development.
AB  - Legume root nodules develop as a result of a symbiotic relationship between the
      plant and nitrogen-fixing rhizobia bacteria in soil. Auxin activity is detected
      in different cell types at different stages of nodule development; as well as an
      enhanced sensitivity to auxin inhibits, which could affect nodule development.
      While some transport and signaling mechanisms that achieve precise spatiotemporal
      auxin output are known, the role of auxin metabolism during nodule development is
      unclear. Using a soybean root lateral organ transcriptome data set, we identified
      distinct nodule enrichment of three genes encoding auxin-deactivating GRETCHEN
      HAGEN 3 (GH3) indole-3-acetic acid (IAA) amido transferase enzymes: GmGH3-11/12,
      GmGH3-14 and GmGH3-15. In vitro enzymatic assays showed that each of these GH3
      proteins preferred IAA and aspartate as acyl and amino acid substrates,
      respectively. GmGH3-15 showed a broad substrate preference, especially with
      different forms of auxin. Promoter:GUS expression analysis indicated that GmGH3
      14 acts primarily in the root epidermis and the nodule primordium where as GmGH3
      15 might act in the vasculature. Silencing the expression of these GH3 genes in
      soybean composite plants led to altered nodule numbers, maturity, and size. Our
      results indicate that these GH3s are needed for proper nodule maturation in
      soybean, but the precise mechanism by which they regulate nodule development
      remains to be explained.

PMID- 29182531
TI  - Different Facets of Body Image Disturbance in Binge Eating Disorder: A Review.
AB  - The goal of the present review is to give an overview of the current findings on
      various facets of body image disturbance in Binge Eating Disorder such as body
      dissatisfaction, overconcern with weight and shape, body-related checking and
      avoidance behavior, misperception of body size, and body-related cognitive bias.
      In addition, treatments for a disturbed body image in BED and evidence of body
      image disturbance in youth with binge eating are reviewed. The results show that
      a disturbed body image in BED is present in the form of overconcern with weight
      and shape. Furthermore, there are hints that body dissatisfaction, as well as
      body-related checking and avoidance behavior, are also impaired. Research
      concerning misperception of body size in BED has been neglected so far, but first
      findings show that individuals with BED rate their own body shape rather
      accurately. Furthermore, there are first hints that body-related cognitive biases
      are present in individuals with BED. Moreover, in children and adolescents, there
      are first hints that body dissatisfaction, as well as shape and weight concerns,
      seem to be associated with loss of control and binge eating. Treatments aimed
      directly at the convertibility of a disturbed body image in BED have revealed
      encouraging outcomes. In conclusion, body image disturbance seems to occur in
      BED, and first studies show that it can be treated effectively.

PMID- 29182532
TI  - Human Skin Permeation Studies with PPARgamma Agonist to Improve Its Permeability
      and Efficacy in Inflammatory Processes.
AB  - Rosacea is the most common inflammatory skin disease. It is characterized by
      erythema, inflammatory papules and pustules, visible blood vessels, and
      telangiectasia. The current treatment has limitations and unsatisfactory results.
      Pioglitazone (PGZ) is an agonist of peroxisome proliferator-activated receptors
      (PPARs), a nuclear receptor that regulates important cellular functions,
      including inflammatory responses. The purpose of this study was to evaluate the
      permeation of PGZ with a selection of penetration enhancers and to analyze its
      effectiveness for treating rosacea. The high-performance liquid chromatography
      (HPLC) method was validated for the quantitative determination of PGZ. Ex vivo
      permeation experiments were realized in Franz diffusion cells using human skin,
      in which PGZ with different penetration enhancers were assayed. The results
      showed that the limonene was the most effective penetration enhancer that
      promotes the permeation of PGZ through the skin. The cytotoxicity studies and the
      Draize test detected cell viability and the absence of skin irritation,
      respectively. The determination of the skin color using a skin colorimetric probe
      and the results of histopathological studies confirmed the ability of PGZ
      limonene to reduce erythema and vasodilation. This study suggests new
      pharmacological indications of PGZ and its possible application in the treatment
      of skin diseases, namely rosacea.

PMID- 29182534
TI  - On-Tree Mango Fruit Size Estimation Using RGB-D Images.
AB  - In-field mango fruit sizing is useful for estimation of fruit maturation and size
      distribution, informing the decision to harvest, harvest resourcing (e.g., tray
      insert sizes), and marketing. In-field machine vision imaging has been used for
      fruit count, but assessment of fruit size from images also requires estimation of
      camera-to-fruit distance. Low cost examples of three technologies for assessment
      of camera to fruit distance were assessed: a RGB-D (depth) camera, a stereo
      vision camera and a Time of Flight (ToF) laser rangefinder. The RGB-D camera was
      recommended on cost and performance, although it functioned poorly in direct
      sunlight. The RGB-D camera was calibrated, and depth information matched to the
      RGB image. To detect fruit, a cascade detection with histogram of oriented
      gradients (HOG) feature was used, then Otsu's method, followed by color
      thresholding was applied in the CIE L*a*b* color space to remove background
      objects (leaves, branches etc.). A one-dimensional (1D) filter was developed to
      remove the fruit pedicles, and an ellipse fitting method employed to identify
      well-separated fruit. Finally, fruit lineal dimensions were calculated using the
      RGB-D depth information, fruit image size and the thin lens formula. A Root Mean
      Square Error (RMSE) = 4.9 and 4.3 mm was achieved for estimated fruit length and
      width, respectively, relative to manual measurement, for which repeated human
      measures were characterized by a standard deviation of 1.2 mm. In conclusion, the
      RGB-D method for rapid in-field mango fruit size estimation is practical in terms
      of cost and ease of use, but cannot be used in direct intense sunshine. We
      believe this work represents the first practical implementation of machine vision
      fruit sizing in field, with practicality gauged in terms of cost and simplicity
      of operation.

PMID- 29182533
TI  - Early Gabapentin Treatment during the Latency Period Increases Convulsive
      Threshold, Reduces Microglial Activation and Macrophage Infiltration in the
      Lithium-Pilocarpine Model of Epilepsy.
AB  - The lithium-pilocarpine model of epilepsy reproduces several features of temporal
      lobe epilepsy in humans, including the chronological timeline of an initial
      latency period followed by the development of spontaneous seizures. Epilepsy
      therapies in humans are implemented, as a rule, after the onset of the
      spontaneous seizures. We here studied the potential effect on epileptogenesis of
      starting an early treatment during the latency period, in order to prevent the
      development of spontaneous seizures. Adult male Wistar rats were treated with 3
      mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once status epilepticus (SE)
      was achieved, it was allowed to last for 20 min, and then motor seizures were
      controlled with the administration of 20 mg/kg diazepam. At 1DPSE (DPSE, days
      post-status epilepticus), animals started to receive 400 mg/kg/day gabapentin or
      saline for 4 days. At 5DPSE, we observed that SE induced an early profuse
      microglial and astroglial reactivity, increased synaptogenic trombospondin-1
      expression and reduced AQP4 expression in astroglial ending feet. Blood brain
      barrier (BBB) integrity seemed to be compromised, as infiltrating NG2+
      macrophages and facilitated access to the CNS was observed by transplanting eGFP+
      blood cells and bone marrow-derived progenitors in the SE animals. The early 4
      day gabapentin treatment successfully reduced microglial cell reactivity and
      blood-borne cell infiltration, without significantly altering the mRNA of
      proinflammatory cytokines IL-1beta and TNFalpha immediately after the treatment.
      After 21DSPE, another group of animals that developed SE and received 4 days of
      gabapentin treatment, were re-exposed to subconvulsive accumulative doses of
      pilocarpine (10 mg/kg/30 min) and were followed by recording the Racine scale
      reached. Early 4-day gabapentin treatment reduced the Racine scale reached by the
      animals, reduced animal mortality, and reduced the number of animals that
      achieved SE (34% vs. 72%). We conclude that early gabapentin treatment following
      SE, during the latency period, is able to reduce neuroinflammation and produces a
      persistent effect that limits seizures and increases convulsive threshold,
      probably by restricting microglial reactivity and spurious synaptogenesis.

PMID- 29182535
TI  - Contextual Exploration of a New Family Caregiver Support Concept for Geriatric
      Settings Using a Participatory Health Research Strategy.
AB  - Family caregivers are the backbone of the long-term care support system within
      the home environment. Comprehensive caregiver support programs require
      collaboration and coordination within the system. A new public health concept,
      Vade Mecum, aims to harmonize and professionalize family caregiver support
      initiatives in geriatric care settings in the Euregion Maas-Rhine. Exploration of
      the new concept recently started in Germany to gain in-depth insight into current
      support and the needs of the geriatric care team and family caregivers. Within
      the context of an exploratory qualitative study, a participatory health research
      (PHR) strategy was applied to make optimal use of experience and knowledge from
      the system. Care professionals, engaged as co-researchers, were responsible for
      decisions about the research question, data collection methods and procedures of
      engaging family caregivers. A research team representing all professions within
      the geriatric department was formed. Research objectives were formulated and an
      appropriate mix of qualitative data collection methods consisting of interviews,
      focus groups and story-telling was chosen. Needs and expectations of the new
      concept, and practical solutions for involving family caregivers were discussed.
      A PHR strategy resulted in initiating a qualitative study in a geriatric care
      setting carried out by care professionals from the department. Knowledge was
      generated in a co-creative manner, and co-researchers were empowered. A
      comprehensive understanding of the system serves as a starting point for
      advancement of the new family caregiver concept.

PMID- 29182536
TI  - Are We Underestimating Benthic Cyanotoxins? Extensive Sampling Results from
      Spain.
AB  - Microcystins (MCs) are potent hepatotoxins, and their presence in water bodies
      poses a threat to wildlife and human populations. Most of the available
      information refers to plankton, and much less is known about microcystins in
      other habitats. To broaden our understanding of the presence and environmental
      distribution of this group of toxins, we conducted extensive sampling throughout
      Spain, under a range of conditions and in distinct aquatic and terrestrial
      habitats. More than half of the tested strains were toxic; concentrations of the
      hepatotoxin were low compared with planktic communities, and the number of toxic
      variants identified in each sample of the Spanish strains ranged from 1-3. The
      presence of microcystins LF and LY (MC-LF and MC-LY) in the tested samples was
      significant, and ranged from 21.4% to 100% of the total microcystins per strain.
      These strains were only detected in cyanobacteria Oscillatoriales and Nostocales.
      We can report, for the first time, seven new species of microcystin producers in
      high mountain rivers and chasmoendolithic communities. This is the first report
      of these species in Geitlerinema and the confirmation of Anatoxin-a in Phormidium
      uncinatum. Our findings show that microcystins are widespread in all habitat
      types, including both aerophytic and endolithic peat bogs and that it is
      necessary to identify all the variants of microcystins in aquatic bodies as the
      commonest toxins sometimes represent a very low proportion of the total.

PMID- 29182538
TI  - Tactile Perception of Roughness and Hardness to Discriminate Materials by
      Friction-Induced Vibration.
AB  - The human fingertip is an exquisitely powerful bio-tactile sensor in perceiving
      different materials based on various highly-sensitive mechanoreceptors
      distributed all over the skin. The tactile perception of surface roughness and
      material hardness can be estimated by skin vibrations generated during a
      fingertip stroking of a surface instead of being maintained in a static position.
      Moreover, reciprocating sliding with increasing velocities and pressures are two
      common behaviors in humans to discriminate different materials, but the question
      remains as to what the correlation of the sliding velocity and normal load on the
      tactile perceptions of surface roughness and hardness is for material
      discrimination. In order to investigate this correlation, a finger-inspired
      crossed-I beam structure tactile tester has been designed to mimic the anthropic
      tactile discrimination behaviors. A novel method of characterizing the fast
      Fourier transform integral (FFT) slope of the vibration acceleration signal
      generated from fingertip rubbing on surfaces at increasing sliding velocity and
      normal load, respectively, are defined as kv and kw, and is proposed to
      discriminate the surface roughness and hardness of different materials. Over
      eight types of materials were tested, and they proved the capability and
      advantages of this high tactile-discriminating method. Our study may find
      applications in investigating humanoid robot perceptual abilities.

PMID- 29182537
TI  - Dynamics of Pathological and Virological Findings During Experimental Calpox
      Virus Infection of Common Marmosets (Callithrix jacchus).
AB  - Experimental intranasal infection of marmosets (Callithrix jacchus) with calpox
      virus results in fatal disease. Route and dose used for viral inoculation of the
      test animals mimics the natural transmission of smallpox, thus representing a
      suitable model to study pathogenesis and to evaluate new vaccines against
      orthopoxvirus infection. However, the pathogenic mechanisms leading to death are
      still unclear. Therefore, our study aimed at investigating the kinetics of
      pathological alterations to clarify the pathogenesis in calpox virus infection.
      Following intranasal inoculation with two different viral doses, common marmosets
      were sacrificed on days 3, 5, 7, 10 and 12 post inoculation. Collected tissue was
      screened using histopathology, immunohistochemistry, transmission electron
      microscopy, and virological assays. Our data suggest that primary replication
      took place in nasal and bronchial epithelia followed by secondary replication in
      submandibular lymph nodes and spleen. Parallel to viremia at day 7, virus was
      detectable in many organs, mainly located in epithelial cells and macrophages, as
      well as in endothelial cells. Based on the onset of clinical signs, the
      histological and ultrastructural lesions and the immunohistochemical distribution
      pattern of the virus, the incubation period was defined to last 11 days, which
      resembles human smallpox. In conclusion, the data indicate that the calpox model
      is highly suitable for studying orthopoxvirus-induced disease.

PMID- 29182539
TI  - Effect of Composition and Thickness on the Perpendicular Magnetic Anisotropy of
      (Co/Pd) Multilayers.
AB  - Magnetic materials with perpendicular magnetic anisotropy (PMA) have wide-ranging
      applications in magnetic recording and sensing devices. Multilayers comprised of
      ferromagnetic and non-magnetic metals (FM-NM) are interesting materials, as their
      magnetic anisotropy depends strongly on composition and growth parameters. In
      this context, (Co/Pd) multilayers have gained huge interest recently due to their
      robustness and tunable PMA. Here, we report a systematic study of the effect of
      composition on the magnetic anisotropy of (Co/Pd) multilayers grown by Direct
      Current (DC) magnetron sputtering. Four different series of (Co/Pd)*10
      multilayers with different thicknesses of Co and Pd were examined. Vibrating
      sample magnetometery was used to determine the magnetic anisotropy of these
      films. X-ray diffraction and transmission electron microscopy experiments were
      performed to understand the structural morphology of the films. Our results
      showed that (Co/Pd)*10 multilayers exhibit PMA when the Co to Pd ratio is less
      than or equal to 1 and the thickness of Co layers is not more than 5 A. Maximum
      effective anisotropy energy is shown by the films with a Co to Pd ratio of 1/3.

PMID- 29182541
TI  - Ceramic-Based 4D Components: Additive Manufacturing (AM) of Ceramic-Based
      Functionally Graded Materials (FGM) by Thermoplastic 3D Printing (T3DP).
AB  - In our study, we investigated the additive manufacturing (AM) of ceramic-based
      functionally graded materials (FGM) by the direct AM technology thermoplastic 3D
      printing (T3DP). Zirconia components with varying microstructures were additively
      manufactured by using thermoplastic suspensions with different contents of pore
      forming agents (PFA), which were co-sintered defect-free. Different materials
      were investigated concerning their suitability as PFA for the T3DP process.
      Diverse zirconia-based suspensions were prepared and used for the AM of single-
      and multi-material test components. All of the samples were sintered defect-free,
      and in the end, we could realize a brick wall-like component consisting of dense
      (<1% porosity) and porous (approx. 5% porosity) zirconia areas to combine
      different properties in one component. T3DP opens the door to the AM of further
      ceramic-based 4D components, such as multi-color, multi-material, or especially,
      multi-functional components.

PMID- 29182540
TI  - Probing Protein Glycation by Chromatography and Mass Spectrometry: Analysis of
      Glycation Adducts.
AB  - Glycation is a non-enzymatic post-translational modification of proteins, formed
      by the reaction of reducing sugars and alpha-dicarbonyl products of their
      degradation with amino and guanidino groups of proteins. Resulted early glycation
      products are readily involved in further transformation, yielding a heterogeneous
      group of advanced glycation end products (AGEs). Their formation is associated
      with ageing, metabolic diseases, and thermal processing of foods. Therefore,
      individual glycation adducts are often considered as the markers of related
      pathologies and food quality. In this context, their quantification in biological
      and food matrices is required for diagnostics and establishment of food
      preparation technologies. For this, exhaustive protein hydrolysis with subsequent
      amino acid analysis is the strategy of choice. Thereby, multi-step enzymatic
      digestion procedures ensure good recoveries for the most of AGEs, whereas tandem
      mass spectrometry (MS/MS) in the multiple reaction monitoring (MRM) mode with
      stable isotope dilution or standard addition represents "a gold standard" for
      their quantification. Although the spectrum of quantitatively assessed AGE
      structures is continuously increases, application of untargeted profiling
      techniques for identification of new products is desired, especially for in vivo
      characterization of anti-glycative systems. Thereby, due to a high glycative
      potential of plant metabolites, more attention needs to be paid on plant-derived
      AGEs.

PMID- 29182543
TI  - Home Hemodialysis (HHD) Treatment as Effective yet Underutilized Treatment
      Modality in the United States.
AB  - End-stage renal disease (ESRD) is a major health burden and its incidence has
      been increasing yearly reaching 120,000 cases in 2014. Home hemodialysis (HHD) is
      a treatment modality option that has been shown to contribute to numerous
      clinical benefits but is largely underutilized due to many contributing factors.
      The purpose of this review paper is to analyze the advantages and disadvantages
      of HHD and the reasons for its low utilization with a special focus on its
      socioeconomic impact as compared to facility hemodialysis. Key factors
      contributing to HHD underutilization are related to the reimbursement system of
      the facility and nephrologists as well as the underutilization of the pre
      dialysis educational benefit. Based on this comprehensive review of the
      literature, we propose several suggestions which may contribute to the expansion
      of HHD treatment modality.

PMID- 29182542
TI  - The Potential of Zebrafish as a Model Organism for Improving the Translation of
      Genetic Anticancer Nanomedicines.
AB  - In the last few decades, the field of nanomedicine applied to cancer has
      revolutionized cancer treatment: several nanoformulations have already reached
      the market and are routinely being used in the clinical practice. In the case of
      genetic nanomedicines, i.e., designed to deliver gene therapies to cancer cells
      for therapeutic purposes, advances have been less impressive. This is because of
      the many barriers that limit the access of the therapeutic nucleic acids to their
      target site, and the lack of models that would allow for an improvement in the
      understanding of how nanocarriers can be tailored to overcome them. Zebrafish has
      important advantages as a model species for the study of anticancer therapies,
      and have a lot to offer regarding the rational development of efficient delivery
      of genetic nanomedicines, and hence increasing the chances of their successful
      translation. This review aims to provide an overview of the recent advances in
      the development of genetic anticancer nanomedicines, and of the zebrafish models
      that stand as promising tools to shed light on their mechanisms of action and
      overall potential in oncology.

PMID- 29182544
TI  - TRIM8: Making the Right Decision between the Oncogene and Tumour Suppressor Role.
AB  - The TRIM8/GERP protein is a member of the TRIM family defined by the presence of
      a common domain structure composed of a tripartite motif including a RING-finger,
      one or two B-box domains, and a coiled-coil motif. The TRIM8 gene maps on
      chromosome 10 within a region frequently found deleted and rearranged in tumours
      and transcribes a 3.0-kB mRNA. Its expression is mostly ubiquitously in murine
      and human tissues, and in epithelial and lymphoid cells, it can be induced by
      IFNgamma. The protein spans 551 aa and is highly conserved during evolution.
      TRIM8 plays divergent roles in many biological processes, including important
      functions in inflammation and cancer through regulating various signalling
      pathways. In regulating cell growth, TRIM8 exerts either a tumour suppressor
      action, playing a prominent role in regulating p53 tumour suppressor activity, or
      an oncogene function, through the positive regulation of the NF-kappaB pathway.
      The molecular mechanisms underlying this dual role in human cancer will be
      discussed in depth in this review, and it will highlight the challenge and
      importance of developing novel therapeutic strategies specifically aimed at
      blocking the pro-oncogenic arm of the TRIM8 signalling pathway without affecting
      its tumour suppressive effects.

PMID- 29182545
TI  - Detection of Abrin Holotoxin Using Novel Monoclonal Antibodies.
AB  - Abrin, a member of the ribosome-inactivating protein family, is produced by the
      Abrus precatorius plant. Having the potential to pose a severe threat to both
      human and animal health, abrin is classified as a Select Agent by the U.S.
      Department of Health and Human Services. However, an immunoassay that is specific
      for intact abrin holotoxin has not yet been reported. In this study, seven new
      monoclonal antibodies (mAbs), designated as Abrin-1 through Abrin-7 have been
      developed. Isotyping analyses indicate these mAbs have IgG1, IgG2a, or IgG2b
      heavy-chains and kappa light-chains. Western blot analyses identified two abrin A
      chain specific mAbs, Abrin-1 and Abrin-2, and four B-chain specific mAbs (Abrin
      3, -5, -6, and -7). A sandwich enzyme-linked immunosorbent assay (ELISA), capable
      of detecting a mixture of abrin isoforms and agglutinins was developed using B
      chain specific Abrin-3 for capture and A-chain specific Abrin-2 as detector. The
      ELISA is highly sensitive and detects 1 ng/mL of the abrin holotoxin in phosphate
      buffered saline, nonfat milk, and whole milk, significantly below concentrations
      that would pose a health concern for consumers. This ELISA also detects native
      abrin in plant extracts with a very low background signal. The new abrin mAbs and
      ELISA should be useful for detecting this potent toxin in the milk supply chain
      and other complex matrices.

PMID- 29182546
TI  - Luminescent Lanthanoid Calixarene Complexes and Materials.
AB  - This review aims to provide an overview of recent examples of lanthanoid
      calixarene complexes incorporated into light-emitting materials. Background
      information on the antenna effect and early work on lanthanoid complexes on
      calixarenes is provided to set the context. Classes of materials discussed
      include polymers, nanoparticles, and metal clusters.

PMID- 29182547
TI  - Gene Silencing of Argonaute5 Negatively Affects the Establishment of the Legume
      Rhizobia Symbiosis.
AB  - The establishment of the symbiosis between legumes and nitrogen-fixing rhizobia
      is finely regulated at the transcriptional, posttranscriptional and
      posttranslational levels. Argonaute5 (AGO5), a protein involved in RNA silencing,
      can bind both viral RNAs and microRNAs to control plant-microbe interactions and
      plant physiology. For instance, AGO5 regulates the systemic resistance of
      Arabidopsis against Potato Virus X as well as the pigmentation of soybean
      (Glycine max) seeds. Here, we show that AGO5 is also playing a central role in
      legume nodulation based on its preferential expression in common bean (Phaseolus
      vulgaris) and soybean roots and nodules. We also report that the expression of
      AGO5 is induced after 1 h of inoculation with rhizobia. Down-regulation of AGO5
      gene in P. vulgaris and G. max causes diminished root hair curling, reduces
      nodule formation and interferes with the induction of three critical symbiotic
      genes: Nuclear Factor Y-B (NF-YB), Nodule Inception (NIN) and Flotillin2 (FLOT2).
      Our findings provide evidence that the common bean and soybean AGO5 genes play an
      essential role in the establishment of the symbiosis with rhizobia.

PMID- 29182549
TI  - Effects of Group Counseling Programs, Cognitive Behavioral Therapy, and Sports
      Intervention on Internet Addiction in East Asia: A Systematic Review and Meta
      Analysis.
AB  - To evaluate the effects of group counseling programs, cognitive behavioral
      therapy (CBT), and sports intervention on Internet addiction (IA), a systematic
      search in ten databases was performed to identify eligible studies without
      language restrictions up to January 2017. A meta-analysis and trial sequential
      analysis (TSA) was performed, respectively. A total of 58 randomized controlled
      trials (RCTs), which included 2871 participants, were incorporated into our meta
      analysis. The results showed that group counseling programs, CBT, and sports
      intervention could significantly reduce IA levels (group counseling program:
      standardized mean difference (SMD), -1.37; 95% confidence interval (CI), -1.89 to
      -0.85; CBT: SMD, -1.88; 95% CI, -2.53 to -1.23; sports intervention: SMD, -1.70;
      95% CI, -2.14 to -1.26). For group counseling programs, this treatment was more
      effective in four dimensions of IA, including time management, interpersonal and
      health issues, tolerance, and compulsive Internet use. For CBT, this treatment
      yielded a positive change in depression, anxiousness, aggressiveness,
      somatization, social insecurity, phobic anxiety, paranoid ideation, and
      psychoticism. For sports intervention, the significant effects were also observed
      in all dimensions of the IA scale. Each of group counseling programs, cognitive
      behavioral therapy, and sports intervention had a significant effect on IA and
      psychopathological symptoms. Sports intervention could improve withdrawal
      symptoms especially.

PMID- 29182548
TI  - Identification of DNA-protein Binding Sites through Multi-Scale Local Average
      Blocks on Sequence Information.
AB  - DNA-protein interactions appear as pivotal roles in diverse biological procedures
      and are paramount for cell metabolism, while identifying them with computational
      means is a kind of prudent scenario in depleting in vitro and in vivo
      experimental charging. A variety of state-of-the-art investigations have been
      elucidated to improve the accuracy of the DNA-protein binding sites prediction.
      Nevertheless, structure-based approaches are limited under the condition without
      3D information, and the predictive validity is still refinable. In this essay, we
      address a kind of competitive method called Multi-scale Local Average Blocks
      (MLAB) algorithm to solve this issue. Different from structure-based routes, MLAB
      exploits a strategy that not only extracts local evolutionary information from
      primary sequences, but also using predicts solvent accessibility. Moreover, the
      construction about predictors of DNA-protein binding sites wields an ensemble
      weighted sparse representation model with random under-sampling. To evaluate the
      performance of MLAB, we conduct comprehensive experiments of DNA-protein binding
      sites prediction. MLAB gives M C C of 0.392 , 0.315 , 0.439 and 0.245 on PDNA
      543, PDNA-41, PDNA-316 and PDNA-52 datasets, respectively. It shows that MLAB
      gains advantages by comparing with other outstanding methods. M C C for our
      method is increased by at least 0.053 , 0.015 and 0.064 on PDNA-543, PDNA-41 and
      PDNA-316 datasets, respectively.

PMID- 29182550
TI  - Evolution of Tandem Repeat Satellite Sequences in Two Closely Related
      Caenorhabditis Species. Diminution of Satellites in Hermaphrodites.
AB  - The availability of the genome sequence of the unisexual (male-female)
      Caenorhabditis nigoni offers an opportunity to compare its non-coding features
      with the related hermaphroditic species Caenorhabditis briggsae; to understand
      the evolutionary dynamics of their tandem repeat sequences (satellites), as a
      result of evolution from the unisexual ancestor. We take advantage of the
      previously developed SATFIND program to build satellite families defined by a
      consensus sequence. The relative number of satellites (satellites/Mb) in C.
      nigoni is 24.6% larger than in C. briggsae. Some satellites in C. nigoni have
      developed from a proto-repeat present in the ancestor species and are conserved
      as an isolated sequence in C. briggsae. We also identify unique satellites which
      occur only once and joint satellite families with a related sequence in both
      species. Some of these families are only found in C. nigoni, which indicates a
      recent appearance; they contain conserved adjacent 5' and 3' regions, which may
      favor transposition. Our results show that the number, length and turnover of
      satellites are restricted in the hermaphrodite C. briggsae when compared with the
      unisexual C. nigoni. We hypothesize that this results from differences in unequal
      recombination during meiotic chromosome pairing, which limits satellite turnover
      in hermaphrodites.

PMID- 29182551
TI  - Transparent and Flexible Capacitors with an Ultrathin Structure by Using Graphene
      as Bottom Electrodes.
AB  - Ultrathin, transparent and flexible capacitors using graphene as the bottom
      electrodes were directly fabricated on polyethylene naphthalate (PEN) substrates.
      ZrO2 dielectric films were deposited on the treated surface of graphene by atomic
      layer deposition (ALD). The deposition process did not introduce any detectible
      defects in the graphene, as indicated by Raman measurements, guaranteeing the
      electrical performances of the graphene electrodes. The Aluminum-doped zinc oxide
      (AZO) films were prepared as the top electrodes using the ALD technique. The
      capacitors presented a high capacitance density (10.3 fF/MUm2 at 10 kHz) and a
      relatively low leakage current (5.3 * 10-6 A/cm2 at 1 V). Bending tests revealed
      that the capacitors were able to work normally at an outward bending radius of 10
      mm without any deterioration of electrical properties. The capacitors exhibited
      an average optical transmittance of close to 70% at visible wavelengths. Thus, it
      opens the door to practical applications in transparent integrated circuits.

PMID- 29182552
TI  - Study on the Anticoagulant or Procoagulant Activities of Type II Phenolic Acid
      Derivatives.
AB  - In this study, three type II phenolic acids (caffeic acid, p-hydroxycinnamic
      acid, and ferulic acid) were used to synthesize a total of 18 phenolic acid
      derivatives. With molecular docking for molecule design and target protein
      (factors) screening, in combination with the confirmation of target proteins
      (factors) by surface plasmon resonance, and the evaluation of haemostatic and
      anticoagulant activities with five blood assays (plasma recalcification time,
      prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin
      time), the data indicated that caffeic acid derivatives showed certain
      anticoagulant or procoagulant activities and that two other series contained
      compounds with the best anticoagulant activities. Using Materials Studio
      analysis, particular functional groups that affect anticoagulant or procoagulant
      activities were revealed, and these conclusions can guide the discovery of
      compounds with better activities.

PMID- 29182553
TI  - Coumarin Derivatives Solvent-Free Synthesis under Microwave Irradiation over
      Heterogeneous Solid Catalysts.
AB  - A suitable methodology of synthesis of coumarin derivatives by Pechmann reaction
      over heterogeneous solid acid catalysts in a free solvent media under microwave
      irradiation is described. Resorcinol, phenol and ethyl acetoacetate were selected
      as model reactants in the Pechmann condensation. The catalytic activity of
      several materials-Amberlyst-15, zeolite beta and sulfonic acid functionalized
      hybrid silica-in solvent-free microwave-assisted synthesis of the corresponding
      coumarin derivatives has been investigated in detail. 7-Hydroxy-4-methylcoumarin
      and 4-methylcoumarin were obtained in 97% and 43% yields, respectively, over
      Amberlyst-15. This was the most active catalyst in the Pechmann reaction under
      studied conditions.

PMID- 29182554
TI  - Alcohol Interactions with Lipid Bilayers.
AB  - We investigate the structural changes to lipid membrane that ensue from the
      addition of aliphatic alcohols with various alkyl tail lengths. Small angle
      neutron diffraction from flat lipid bilayers that are hydrated through water
      vapor has been employed to eliminate possible artefacts of the membrane curvature
      and the alcohol's membrane-water partitioning. We have observed clear changes to
      membrane structure in both transversal and lateral directions. Most importantly,
      our results suggest the alteration of the membrane-water interface. The water
      encroachment has shifted in the way that alcohol loaded bilayers absorbed more
      water molecules when compared to the neat lipid bilayers. The experimental
      results have been corroborated by molecular dynamics simulations to reveal
      further details. Namely, the order parameter profiles have been fruitful in
      correlating the mechanical model of structural changes to the effect of
      anesthesia.

PMID- 29182555
TI  - Characterization and Computation of Yb/TiO2 and Its Photocatalytic Degradation
      with Benzohydroxamic Acid.
AB  - Yb-doped TiO2 (Yb/TiO2) compositions were synthesized by sol-gel method, and the
      prepared materials were characterized by X-ray Diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS), UV-visible diffuse-reflectance spectrum (UV-Vis
      DRS), transmission electron microscope (TEM) and high resolution transmission
      electron microscope (HRTEM), energy dispersive spectrometer (EDS), and N2
      adsorption. A beneficiation reagent of benzohydroxamic acid (BHA) was used to
      test the photocatalytic activity of Yb/TiO2. The characterizations indicate that
      the doping of Yb could inhibit the crystal growth of TiO2, enhance the specific
      surface area, increase the binding energy of Ti2p, and also slightly expand the
      adsorption ranges to visible light. Furthermore, the computation of band
      structure also indicates that Yb-doped TiO2 could make the forbidden band
      narrower than pure anatase TiO2, which presents a red shift in the absorption
      spectrum. As a result of the photodegradation experiment on BHA, Yb/TiO2 (0.50%
      in mass) sintered at 450  degrees C displayed the highest catalytic activity for
      BHA when compared with pure TiO2 or other doped Yb/TiO2 compositions, and more
      than 89.2% of the total organic carbon was removed after 120 min. Almost all
      anions, including Cl-, HCO3-, NO3-, and SO42-, inhibited the degradation of BHA
      by Yb/TiO2, and their inhibition effects followed the order of HCO3- > NO3- >
      SO42- > Cl-. Cations of Na+, K+, Ca2+, and Mg2+ displayed a slight suppressing
      effect due to the impact of Cl- coexisting in the solution. In addition, Yb/TiO2
      maintained a high photocatalytic ability with respect to BHA after four runs. It
      is hypothesized that .OH is one of the main species involved in the
      photodegradation of BHA, and the mutual transformation of Yb3+ and Yb2+ could
      promote the separation of electron-hole pairs.

PMID- 29182556
TI  - Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal
      Life.
AB  - Alcohol (ethanol) disturbs cognitive functions including learning and memory in
      humans, non-human primates, and laboratory animals such as rodents. As studied in
      animals, cellular mechanisms for learning and memory include bidirectional
      synaptic plasticity, long-term potentiation (LTP), and long-term depression
      (LTD), primarily in the hippocampus. Most of the research in the field of alcohol
      has analyzed the effects of ethanol on LTP; however, with recent advances in the
      understanding of the physiological role of LTD in learning and memory, some
      authors have examined the effects of ethanol exposure on this particular signal.
      In the present review, I will focus on hippocampal LTD recorded in rodents and
      the effects of fetal alcohol exposure on this signal. A synthesis of the findings
      indicates that prenatal ethanol exposure disturbs LTD concurrently with LTP in
      offspring and that both glutamatergic and gamma-aminobutyric acid (GABA)
      neurotransmissions are altered and contribute to LTD disturbances. Although the
      ultimate mode of action of ethanol on these two transmitter systems is not yet
      clear, novel suggestions have recently appeared in the literature.

PMID- 29182557
TI  - Effect of Dietary Acidolysis-Oxidized Konjac Glucomannan Supplementation on Serum
      Immune Parameters and Intestinal Immune-Related Gene Expression of Schizothorax
      prenanti.
AB  - The present study was conducted to investigate the effects of dietary acidolysis
      oxidized konjac glucomannan (A-OKGM) (0%, 0.4%, 0.8%, and 1.6%) supplementation
      on the immunity and expression of immune-related genes in Schizothorax prenanti.
      After feeding for eight weeks, the serum and guts were used for measurement of
      biochemical parameters, and immune-related gene expression in the gut were also
      analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). C
      reactive protein and IgM levels were significantly higher in the A-OKGM fed
      groups than in the control group, regardless of the dosage. The 0.4% and 1.6% A
      OKGM groups showed significant up-regulation of tumor necrosis factor alpha
      (TNFalpha) in the anterior gut. The 0.8% and 1.6% A-OKGM groups also showed
      significantly enhanced TNFalpha expression in the mid- and distal guts.
      Interleukin-1beta (IL-1beta) expression in the anterior gut of fish fed with 0.4%
      and 1.6% A-OKGM diets was significantly enhanced. The 0.8% and 1.6% A-OKGM diets
      resulted in significantly increased the expression of IL-1beta in the distal gut.
      Similarly, the interleukin-6 (IL-6) messenger RNA (mRNA) levels in the 0.4% and
      1.6% diet groups were significantly higher in the anterior gut. The 0.8% and 1.6%
      A-OKGM diet groups showed significant induction of IL-6 gene expression in the
      distal gut. A-OKGM modified from KGM can act as an immunostimulant to enhance the
      immunity of S. prenanti.

PMID- 29182558
TI  - An Isoxazole Chalcone Derivative Enhances Melanogenesis in B16 Melanoma Cells via
      the Akt/GSK3beta/beta-Catenin Signaling Pathways.
AB  - Plants or plant-derived products have been routinely used in several traditional
      medicine systems for vitiligo treatment. It is well-known that melanogenesis can
      be promoted by certain flavonoid compounds isolated from the traditional Uyghur
      medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid
      compounds, has become an interesting target for the development of anti-vitiligo
      agents. A series of novel isoxazole chalcone derivatives have been designed,
      synthesized, and evaluated for biological activities by our group. Among them,
      derivative 1-(4-((3-phenylisoxazol-5-yl)methoxy)phenyl)-3-phenylprop-2-en-1-one
      (PMPP) was identified as a potent tyrosinase activator with better activity and
      lower toxicity than the positive control 8-methoxypsoralen (8-MOP) in this study.
      Further investigations revealed that Akt and GSK3beta were the signaling pathways
      involved in the hyperpigmentation of PMPP. Overall, these studies may provide a
      convenient and novel approach for the further development of anti-vitiligo
      agents.

PMID- 29182559
TI  - Study of Perfluorophosphonic Acid Surface Modifications on Zinc Oxide
      Nanoparticles.
AB  - In this study, perfluorinated phosphonic acid modifications were utilized to
      modify zinc oxide (ZnO) nanoparticles because they create a more stable surface
      due to the electronegativity of the perfluoro head group. Specifically, 12
      pentafluorophenoxydodecylphosphonic acid, 2,3,4,5,6-pentafluorobenzylphosphonic
      acid, and (1H,1H,2H,2H-perfluorododecyl)phosphonic acid have been used to form
      thin films on the nanoparticle surfaces. The modified nanoparticles were then
      characterized using infrared spectroscopy, X-ray photoelectron spectroscopy, and
      solid-state nuclear magnetic resonance spectroscopy. Dynamic light scattering and
      scanning electron microscopy-energy dispersive X-ray spectroscopy were utilized
      to determine the particle size of the nanoparticles before and after
      modification, and to analyze the film coverage on the ZnO surfaces, respectively.
      Zeta potential measurements were obtained to determine the stability of the ZnO
      nanoparticles. It was shown that the surface charge increased as the alkyl chain
      length increases. This study shows that modifying the ZnO nanoparticles with
      perfluorinated groups increases the stability of the phosphonic acids adsorbed on
      the surfaces. Thermogravimetric analysis was used to distinguish between
      chemically and physically bound films on the modified nanoparticles. The higher
      weight loss for 12-pentafluorophenoxydodecylphosphonic acid and (1H,1H,2H,2H
      perfluorododecyl)phosphonic acid modifications corresponds to a higher surface
      concentration of the modifications, and, ideally, higher surface coverage. While
      previous studies have shown how phosphonic acids interact with the surfaces of
      ZnO, the aim of this study was to understand how the perfluorinated groups can
      tune the surface properties of the nanoparticles.

PMID- 29182560
TI  - Preparation of Al/Fe-Pillared Clays: Effect of the Starting Mineral.
AB  - Four natural clays were modified with mixed polyoxocations of Al/Fe for
      evaluating the effect of the physicochemical properties of the starting materials
      (chemical composition, abundance of expandable clay phases, cationic exchange
      capacity and textural properties) on final physicochemical and catalytic
      properties of Al/Fe-PILCs. The aluminosilicate denoted C2 exhibited the highest
      potential as starting material in the preparation of Al/Fe-PILC catalysts, mainly
      due to its starting cationic exchange capacity (192 meq/100 g) and the
      dioctahedral nature of the smectite phase. These characteristics favored the
      intercalation of the mixed (Al13-x/Fex)7+ Keggin-type polyoxocations, stabilizing
      a basal spacing of 17.4 A and high increase of the BET surface (194 m2/g), mainly
      represented in microporous content. According to H2-TPR analyses, catalytic
      performance of the incorporated Fe in the Catalytic Wet Peroxide Oxidation (CWPO)
      reaction strongly depends on the level of location in mixed Al/Fe pillars.
      Altogether, such physicochemical characteristics promoted high performance in
      CWPO catalytic degradation of methyl orange in aqueous medium at very mild
      reaction temperatures (25.0 +/- 1.0  degrees C) and pressure (76 kPa), achieving
      TOC removal of 52% and 70% of azo-dye decolourization in only 75 min of reaction
      under very low concentration of clay catalyst (0.05 g/L).

PMID- 29182561
TI  - Analysis of MicroRNA Expression in Newborns with Differential Birth Weight Using
      Newborn Screening Cards.
AB  - Birth weight is an early predictor for metabolic diseases and microRNAs (miRNAs)
      are proposed as fetal programming participants. To evaluate the use of dried
      blood spots (DBS) on newborn screening cards (NSC) as a source of analyzable
      miRNAs, we optimized a commercial protocol to recover total miRNA from normal
      birth weight (NBW, n = 17-20), low birth weight (LBW, n = 17-20) and high birth
      weight (macrosomia, n = 17-20) newborns and analyzed the relative expression of
      selected miRNAs by stem-loop RT-qPCR. The possible role of miRNAs on the fetal
      programming of metabolic diseases was explored by bioinformatic tools. The
      optimized extraction of RNA resulted in a 1.2-fold enrichment of miRNAs respect
      to the commercial kit. miR-33b and miR-375 were overexpressed in macrosomia 9.8
      fold (p < 0.001) and 1.7-fold, (p < 0.05), respectively and miR-454-3p was
      overexpressed in both LBW and macrosomia (19.7-fold, p < 0.001 and 10.8-fold, p <
      0.001, respectively), as compared to NBW. Potential target genes for these miRNAs
      are associated to cyclic-guanosine monophosphate (cGMP)-dependent protein kinase
      (PKG), mitogen-activated protein kinase (MAPK), type 2 diabetes, transforming
      growth factor-beta (TGF-beta)and Forkhead box O protein (FoxO) pathways. In
      summary, we improved a protocol for analyzing miRNAs from NSC and provide the
      first evidence that birth weight modifies the expression of miRNAs associated to
      adult metabolic dysfunctions. Our work suggests archived NSC are an invaluable
      resource in the search for fetal programming biomarkers.

PMID- 29182562
TI  - Simple Screening of Listeria monocytogenes Based on a Fluorescence Assay via a
      Laminated Lab-On-Paper Chip.
AB  - Monitoring food safety is essential for protecting the health and safety of
      consumers. Conventional methods used are time consuming and laborious, requiring
      anywhere from three to seven days to obtain results. Thus, better monitoring
      methods are required. In this study, a laminated lab-on-paper chip was developed,
      and its use for the screening of ready-to-eat seafood was demonstrated. The assay
      on a chip was based on loop-mediated isothermal DNA amplification (LAMP) of the
      hly gene of Listeria monocytogenes and fluorescence signal detection via SYBR
      GoldTM. Overall assay processes were completed in 4.5 h., (including 3.5 h.
      incubation for the bacteria enrichment, direct DNA amplification with no DNA
      extraction, and signal detection), without relying on standard laboratory
      facilities. Only positive samples induced fluorescence signals on chip upon
      illumination with UV light (lambda = 460). The method has a limit of detection of
      100 copies of L. monocytogenes DNA per 50 g of sample. No cross-reactivity was
      observed in samples contaminated with other bacteria. On-site monitoring of the
      seafood products using this chip revealed that one of 30 products from low
      sanitation vendors (3.33%) were contaminated, and these agreed with the results
      of PCR. The results demonstrated a benefit of this chip assay for practical on
      site monitoring.

PMID- 29182563
TI  - Development of a High Precision Displacement Measurement System by Fusing a Low
      Cost RTK-GPS Sensor and a Force Feedback Accelerometer for Infrastructure
      Monitoring.
AB  - A displacement measurement system fusing a low cost real-time kinematic global
      positioning system (RTK-GPS) receiver and a force feedback accelerometer is
      proposed for infrastructure monitoring. The proposed system is composed of a
      sensor module, a base module and a computation module. The sensor module consists
      of a RTK-GPS rover and a force feedback accelerometer, and is installed on a
      target structure like conventional RTK-GPS sensors. The base module is placed on
      a rigid ground away from the target structure similar to conventional RTK-GPS
      bases, and transmits observation messages to the sensor module. Then, the initial
      acceleration, velocity and displacement responses measured by the sensor module
      are transmitted to the computation module located at a central monitoring
      facility. Finally, high precision and high sampling rate displacement, velocity,
      and acceleration are estimated by fusing the acceleration from the accelerometer,
      the velocity from the GPS rover, and the displacement from RTK-GPS. Note that the
      proposed displacement measurement system can measure 3-axis acceleration,
      velocity as well as displacement in real time. In terms of displacement, the
      proposed measurement system can estimate dynamic and pseudo-static displacement
      with a root-mean-square error of 2 mm and a sampling rate of up to 100 Hz. The
      performance of the proposed system is validated under sinusoidal, random and
      steady-state vibrations. Field tests were performed on the Yeongjong Grand Bridge
      and Yi Sun-sin Bridge in Korea, and the Xihoumen Bridge in China to compare the
      performance of the proposed system with a commercial RTK-GPS sensor and other
      data fusion techniques.

PMID- 29182564
TI  - Oral Mucositis in Pediatric Patients in Treatment for Acute Lymphoblastic
      Leukemia.
AB  - Oral mucositis in oncologic patients is the most undesirable event of the
      chemotherapeutic treatment. This study aimed to identify damage to the oral
      cavity resulting from chemotherapy in pediatric patients with acute lymphoblastic
      leukemia (ALL). This is a prospective study with a sample of 42 children and
      adolescents evaluated for 10 consecutive weeks after diagnosis. The modified Oral
      Assessment Guide (OAG) was used, and data were analyzed by Spearman's rank
      correlation coefficient (alpha = 5%). Changes to the normal lips and saliva were
      positively related to an increase in the OAG score during all 10 weeks of
      evaluation. Alterations to the labial mucosa were correlated with an increase in
      the OAG score from the 2nd to 10th week, which was also found for changes in the
      tongue and in the swallowing function in Weeks 1, 6, 8, 9, and 10 and for gum
      changes from the 5th to 7th week. No significant vocal changes were correlated
      with the total OAG score at any point during the monitoring period. Changes in
      lips, cheek and/or palatal mucosa, labial mucosa, and gum areas and in swallowing
      function were positively correlated with an increase in the severity of oral
      mucositis in patients with ALL after beginning chemotherapeutic treatment.

PMID- 29182565
TI  - PPARgamma Modulates Long Chain Fatty Acid Processing in the Intestinal
      Epithelium.
AB  - Nuclear receptor PPARgamma affects lipid metabolism in several tissues, but its
      role in intestinal lipid metabolism has not been explored. As alterations have
      been observed in the plasma lipid profile of ad libitum fed intestinal epithelium
      specific PPARgamma knockout mice (iePPARgammaKO), we submitted these mice to
      lipid gavage challenges. Within hours after gavage with long chain unsaturated
      fatty acid (FA)-rich canola oil, the iePPARgammaKO mice had higher plasma free FA
      levels and lower gastric inhibitory polypeptide levels than their wild-type (WT)
      littermates, and altered expression of incretin genes and lipid metabolism
      associated genes in the intestinal epithelium. Gavage with the medium chain
      saturated FA-rich coconut oil did not result in differences between the two
      genotypes. Furthermore, the iePPARgammaKO mice did not exhibit defective lipid
      uptake and stomach emptying; however, their intestinal transit was more rapid
      than in WT mice. When fed a canola oil-rich diet for 4.5 months, iePPARgammaKO
      mice had higher body lean mass than the WT mice. We conclude that intestinal
      epithelium PPARgamma is activated preferentially by long chain unsaturated FAs
      compared to medium chain saturated FAs. Furthermore, we hypothesize that the
      iePPARgammaKO phenotype originates from altered lipid metabolism and release in
      epithelial cells, as well as changes in intestinal motility.

PMID- 29182566
TI  - Insights into Insulin Fibril Assembly at Physiological and Acidic pH and Related
      Amyloid Intrinsic Fluorescence.
AB  - Human insulin is a widely used model protein for the study of amyloid formation
      as both associated to insulin injection amyloidosis in type II diabetes and
      highly prone to form amyloid fibrils in vitro. In this study, we aim to gain new
      structural insights into insulin fibril formation under two different aggregating
      conditions at neutral and acidic pH, using a combination of fluorescence,
      circular dichroism, Fourier-transform infrared spectroscopy, and transmission
      electron miscroscopy. We reveal that fibrils formed at neutral pH are
      morphologically different from those obtained at lower pH. Moreover, differences
      in FTIR spectra were also detected. In addition, only insulin fibrils formed at
      neutral pH showed the characteristic blue-green fluorescence generally associated
      to amyloid fibrils. So far, the molecular origin of this fluorescence phenomenon
      has not been clarified and different hypotheses have been proposed. In this
      respect, our data provide experimental evidence that allow identifying the
      molecular origin of such intrinsic property.

PMID- 29182567
TI  - Mathematical Model for Localised and Surface Heat Flux of the Human Body Obtained
      from Measurements Performed with a Calorimetry Minisensor.
AB  - The accuracy of the direct and local measurements of the heat power dissipated by
      the surface of the human body, using a calorimetry minisensor, is directly
      related to the calibration rigor of the sensor and the correct interpretation of
      the experimental results. For this, it is necessary to know the characteristics
      of the body's local heat dissipation. When the sensor is placed on the surface of
      the human body, the body reacts until a steady state is reached. We propose a
      mathematical model that represents the rate of heat flow at a given location on
      the surface of a human body by the sum of a series of exponentials: W(t) = A0 +
      ?Aiexp(-t/taui). In this way, transient and steady states of heat dissipation can
      be interpreted. This hypothesis has been tested by simulating the operation of
      the sensor. At the steady state, the power detected in the measurement area (4
      cm2) varies depending on the sensor's thermostat temperature, as well as the
      physical state of the subject. For instance, for a thermostat temperature of 24 
      degrees C, this power can vary between 100-250 mW in a healthy adult. In the
      transient state, two exponentials are sufficient to represent this dissipation,
      with 3 and 70 s being the mean values of its time constants.

PMID- 29182568
TI  - A Quartz Crystal Microbalance Immunosensor for Stem Cell Selection and
      Extraction.
AB  - A cost-effective immunosensor for the detection and isolation of dental pulp stem
      cells (DPSCs) based on a quartz crystal microbalance (QCM) has been developed.
      The recognition mechanism relies on anti-CD34 antibodies, DPSC-specific
      monoclonal antibodies that are anchored on the surface of the quartz crystals.
      Due to its high specificity, real time detection, and low cost, the proposed
      technology has a promising potential in the field of cell biology, for the
      simultaneous detection and sorting of stem cells from heterogeneous cell samples.
      The QCM surface was properly tailored through a biotinylated self-assembled
      monolayer (SAM). The biotin-avidin interaction was used to immobilize the
      biotinylated anti-CD34 antibody on the gold-coated quartz crystal. After antibody
      immobilization, a cellular pellet, with a mixed cell population, was analyzed;
      the results indicated that the developed QCM immunosensor is highly specific,
      being able to detect and sort only CD34+ cells. Our study suggests that the
      proposed technology can detect and efficiently sort any kind of cell from samples
      with high complexity, being simple, selective, and providing for more convenient
      and time-saving operations.

PMID- 29182569
TI  - Knee Impedance Modulation to Control an Active Orthosis Using Insole Sensors.
AB  - Robotic devices for rehabilitation and gait assistance have greatly advanced with
      the objective of improving both the mobility and quality of life of people with
      motion impairments. To encourage active participation of the user, the use of
      admittance control strategy is one of the most appropriate approaches, which
      requires methods for online adjustment of impedance components. Such approach is
      cited by the literature as a challenge to guaranteeing a suitable dynamic
      performance. This work proposes a method for online knee impedance modulation,
      which generates variable gains through the gait cycle according to the users'
      anthropometric data and gait sub-phases recognized with footswitch signals. This
      approach was evaluated in an active knee orthosis with three variable gain
      patterns to obtain a suitable condition to implement a stance controller: two
      different gain patterns to support the knee in stance phase, and a third pattern
      for gait without knee support. The knee angle and torque were measured during the
      experimental protocol to compare both temporospatial parameters and kinematics
      data with other studies of gait with knee exoskeletons. The users rated scores
      related to their satisfaction with both the device and controller through QUEST
      questionnaires. Experimental results showed that the admittance controller
      proposed here offered knee support in 50% of the gait cycle, and the walking
      speed was not significantly different between the three gain patterns (p =
      0.067). A positive effect of the controller on users regarding safety during gait
      was found with a score of 4 in a scale of 5. Therefore, the approach demonstrates
      good performance to adjust impedance components providing knee support in stance
      phase.

PMID- 29182570
TI  - Effect of Shot Noise on Simultaneous Sensing in Frequency Division Multiplexed
      Diffuse Optical Tomographic Imaging Process.
AB  - Diffuse optical tomography (DOT) has been studied for use in the detection of
      breast cancer, cerebral oxygenation, and cognitive brain signals. As optical
      imaging studies have increased significantly, acquiring imaging data in real time
      has become increasingly important. We have developed frequency-division
      multiplexing (FDM) DOT systems to analyze their performance with respect to
      acquisition time and imaging quality, in comparison with the conventional time
      division multiplexing (TDM) DOT. A large tomographic area of a cylindrical
      phantom 60 mm in diameter could be successfully reconstructed using both TDM DOT
      and FDM DOT systems. In our experiment with 6 source-detector (S-D) pairs, the
      TDM DOT and FDM DOT systems required 6.18 and 1 s, respectively, to obtain a
      single tomographic data set. While the absorption coefficient of the
      reconstruction image was underestimated in the case of the FDM DOT, we
      experimentally confirmed that the abnormal region can be clearly distinguished
      from the background phantom using both methods.

PMID- 29182571
TI  - Graphene Oxide-Silver Nanoparticles Nanocomposite Stimulates Differentiation in
      Human Neuroblastoma Cancer Cells (SH-SY5Y).
AB  - Recently, graphene and graphene related nanocomposite receive much attention due
      to high surface-to-volume ratio, and unique physiochemical and biological
      properties. The combination of metallic nanoparticles with graphene-based
      materials offers a promising method to fabricate novel graphene-silver hybrid
      nanomaterials with unique functions in biomedical nanotechnology, and
      nanomedicine. Therefore, this study was designed to prepare graphene oxide (GO)
      silver nanoparticles (AgNPs) nanocomposite (GO-AgNPs) containing two different
      nanomaterials in single platform with distinctive properties using luciferin as
      reducing agents. In addition, we investigated the effect of GO-AgNPs on
      differentiation in SH-SY5Y cells. The synthesized GO-AgNPs were characterized by
      ultraviolet-visible absorption spectroscopy (UV-vis), X-ray diffraction (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM) and
      Raman spectroscopy. The differentiation was confirmed by series of cellular and
      biochemical assays. The AgNPs were distributed uniformly on the surface of
      graphene oxide with an average size of 25 nm. As prepared GO-AgNPOs induces
      differentiation by increasing the expression of neuronal differentiation markers
      and decreasing the expression of stem cell markers. The results indicated that
      the redox biology involved the expression of various signaling molecules, which
      play an important role in differentiation. This study suggests that GO-AgNP
      nanocomposite could stimulate differentiation of SH-SY5Y cells. Furthermore,
      understanding the mechanisms of differentiation of neuroblastoma cells could
      provide new strategies for cancer and stem cell therapies. Therefore, these
      studies suggest that GO-AgNPs could target specific chemotherapy-resistant cells
      within a tumor.

PMID- 29182572
TI  - Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Liver
      Lipidomics.
AB  - BACKGROUND: The aim of this study was to characterize the disorder of lipid
      metabolism in hepatocellular carcinoma (HCC). HCC is a worldwide disease. The
      research into the disorder of lipid metabolism in HCC is very limited. Study of
      lipid metabolism in liver cancer tissue may have the potential to provide new
      insight into HCC mechanisms. METHODS: A lipidomics study of HCC based on Ultra
      high performance liquid chromatography-electronic spray ionization-QTOF mass
      spectrometer (UPLC-ESI-QTOF MS) and Matrix assisted laser desorption ionization
      fourier transform ion cyclotron resonance mass spectrometer (MALDI-FTICR MS) was
      performed. RESULTS: Triacylglycerols (TAGs) with the number of double bond (DB) >
      2 (except 56:5 and 56:4 TAG) were significantly down-regulated; conversely,
      others (except 52:2 TAG) were greatly up-regulated in HCC tissues. Moreover, the
      more serious the disease was, the higher the saturated TAG concentration and the
      lower the polyunsaturated TAG concentration were in HCC tissues. The
      phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol
      (PI) were altered in a certain way. Sphingomyelin (SM) was up-regulated and
      ceramide (Cer) were down-regulated in HCC tissues. CONCLUSIONS: To our knowledge,
      this is the first such report showing a unique trend of TAG, PC, PE and PI. The
      use of polyunsaturated fatty acids, like eicosapentanoic and docosahexanoic acid,
      as supplementation, proposed for the treatment of Non-alcoholic steatohepatitis
      (NASH), may also be effective for the treatment of HCC.

PMID- 29182573
TI  - Room-Temperature H2 Gas Sensing Characterization of Graphene-Doped Porous Silicon
      via a Facile Solution Dropping Method.
AB  - In this study, a graphene-doped porous silicon (G-doped/p-Si) substrate for low
      ppm H2 gas detection by an inexpensive synthesis route was proposed as a
      potential noble graphene-based gas sensor material, and to understand the sensing
      mechanism. The G-doped/p-Si gas sensor was synthesized by a simple capillary
      force-assisted solution dropping method on p-Si substrates, whose porosity was
      generated through an electrochemical etching process. G-doped/p-Si was fabricated
      with various graphene concentrations and exploited as a H2 sensor that was
      operated at room temperature. The sensing mechanism of the sensor with/without
      graphene decoration on p-Si was proposed to elucidate the synergetic gas sensing
      effect that is generated from the interface between the graphene and p-type
      silicon.

PMID- 29182574
TI  - Contribution of Dietary Supplements to Nutritional Adequacy in Race/Ethnic
      Population Subgroups in the United States.
AB  - The U.S. Centers for Disease Control and Prevention has reported that nutritional
      deficiencies in the U.S. population vary by age, gender, and race/ethnicity, and
      could be as high as nearly one third of certain population groups. Based on
      nationally representative data in 10,698 adults from National Health and
      Nutrition Examination Surveys (NHANES) primarily from 2009-2012, assessments were
      made of race/ethnic differences in the impact of dietary supplements on nutrient
      intake and prevalence of inadequacies. Compared to food alone, use of any dietary
      supplement plus food was associated with significantly higher intakes of 14 to 16
      of 19 nutrients examined in all race/ethnic groups; and significantly (p < 0.01)
      reduced rates of inadequacy for 8/17 nutrients examined in non-Hispanic whites,
      but only 3-4/17 nutrients (calcium, and vitamins A, D, and E) for other
      race/ethnic groups. Across race/ethnic groups an increased prevalence of intakes
      above the Tolerable Upper Intake Level (UL) was seen for 1-9/13 nutrients, but
      all were less than 5% of the population. In conclusion, use of dietary
      supplements is associated with increased micronutrient intake, decreased nutrient
      inadequacies, and slight increases in prevalence above the UL in all
      race/ethnicities examined, with greater benefits among non-Hispanic whites.

PMID- 29182575
TI  - Modification of Bacterial Cellulose Biofilms with Xylan Polyelectrolytes.
AB  - The effect of the addition of two [4-butyltrimethylammonium]-xylan chloride
      polyelectrolytes (BTMAXs) on bacterial cellulose (BC) was evaluated. The first
      strategy was to add the polyelectrolytes to the culture medium together with a
      cell suspension of the bacterium. After one week of cultivation, the films were
      collected and purified. The second approach consisted of obtaining a purified and
      homogenized BC, to which the polyelectrolytes were added subsequently. The films
      were characterized in terms of tear and burst indexes, optical properties,
      surface free energy, static contact angle, Gurley porosity, SEM, X-ray
      diffraction and AFM. Although there are small differences in mechanical and
      optical properties between the nanocomposites and control films, the films
      obtained by BC synthesis in the presence of BTMAXs were remarkably less opaque,
      rougher, and had a much lower specular gloss. The surface free energy depends on
      the BTMAXs addition method. The crystallinity of the composites is lower than
      that of the control material, with a higher reduction of this parameter in the
      composites obtained by adding the BTMAXs to the culture medium. In view of these
      results, it can be concluded that BC-BTMAX composites are a promising new
      material, for example, for paper restoration.

PMID- 29182576
TI  - Nut Consumption and Cardiovascular Risk Factors: A Cross-Sectional Study in a
      Mediterranean Population.
AB  - : Nuts are often considered beneficial for health, yet few studies have examined
      determinants of their intake and the associations between nut consumption and
      various cardiovascular disease risk factors. The aim of this study was to
      identify factors associated with nut intake in a Mediterranean population, in
      Croatia, and to investigate the association of nut intake and various
      cardiovascular risk factors. METHODS: Subjects from the Island of Vis, Island of
      Korcula and the City of Split were included in this cross-sectional study (n =
      4416 in total; 4011 without known cardiovascular disease). Survey responses,
      medical records and clinically relevant measurements were utilized. Multivariate
      ordinal and logistic regression models were used in the analysis, adjusting for
      known confounding factors. RESULTS: As low as 5% of all subjects reported daily,
      and 11% reported weekly, nut consumption. The characteristics associated with
      more frequent nut intake were female gender (Odds ratio (OR) = 1.39; 95%
      confidence interval (CI) 1.19-1.62), highest level of education (1.42; 1.15-1.76)
      and material status (1.58; 1.29-1.93), smoking abstinence (1.21; 1.04-1.42 in
      never-smokers and 1.22; 1.02-1.46 in ex-smokers), Mediterranean diet adherence
      (1.87; 1.62-2.15), and absence of central obesity (1.29; 1.09-1.53), absence of
      diabetes (1.30; 1.02-1.66) and metabolic syndrome (1.17; 1.01-1.36). Subjects who
      consumed nuts had more favorable waist-to-height (overall p = 0.036) and waist-to
      hip ratios (0.033), lesser odds of elevated fibrinogen (p < 0.001 in both weekly
      and monthly nut consumers) and reduced high-density lipoprotein (HDL) cholesterol
      (p = 0.026), compared to non-consumers. CONCLUSIONS: It appears that frequent nut
      consumption is an integral part of a healthy lifestyle and better socioeconomic
      status. A beneficial association of nut intake with cardiovascular risk factors
      was confirmed in this study.

PMID- 29182577
TI  - Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma
      haematobium Infection.
AB  - Schistosoma haematobium is a human blood fluke causing a chronic infection called
      urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC)
      constitutes chronic sequelae of this infection, and S. haematobium infection is
      accounted as a risk factor for this type of cancer. This infection is considered
      a neglected tropical disease and is endemic in numerous countries in Africa and
      the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic
      molecules are metabolized to active quinones that induce modifications in DNA.
      The cytochrome P450 (CYP) enzymes are a superfamily of mono-oxygenases involved
      in estrogen biosynthesis and metabolism, the generation of DNA damaging
      procarcinogens, and the response to anti-estrogen therapies. IL6 Interleukin-6
      (IL-6) is a pleiotropic cytokine expressed in various tissues. This cytokine is
      largely expressed in the female urogenital tract as well as reproductive organs.
      Very high or very low levels of IL-6 are associated with estrogen metabolism
      imbalance. In the present study, we investigated the polymorphic variants in the
      CYP2D6 gene and the C-174G promoter polymorphism of the IL-6 gene on S.
      haematobium-infected children patients from Guine Bissau. CYP2D6 inactivated
      alleles (28.5%) and IL6G-174C (13.3%) variants were frequent in S. haematobium
      infected patients when compared to previously studied healthy populations (4.5%
      and 0.05%, respectively). Here we discuss our recent findings on these
      polymorphisms and whether they can be predictive markers of schistosome infection
      and/or represent potential biomarkers for urogenital schistosomiasis associated
      bladder cancer and infertility.

PMID- 29182578
TI  - Dietary Sialyllactose Influences Sialic Acid Concentrations in the Prefrontal
      Cortex and Magnetic Resonance Imaging Measures in Corpus Callosum of Young Pigs.
AB  - Sialic acid (SA) is a key component of gangliosides and neural cell adhesion
      molecules important during neurodevelopment. Human milk contains SA in the form
      of sialyllactose (SL) an abundant oligosaccharide. To better understand the
      potential role of dietary SL on neurodevelopment, the effects of varying doses of
      dietary SL on brain SA content and neuroimaging markers of development were
      assessed in a newborn piglet model. Thirty-eight male pigs were provided one of
      four experimental diets from 2 to 32 days of age. Diets were formulated to
      contain: 0 mg SL/L (CON), 130 mg SL/L (LOW), 380 mg SL/L (MOD) or 760 mg SL/L
      (HIGH). At 32 or 33 days of age, all pigs were subjected to magnetic resonance
      imaging (MRI) to assess brain development. After MRI, pig serum and brains were
      collected and total, free and bound SA was analyzed. Results from this study
      indicate dietary SL influenced (p = 0.05) bound SA in the prefrontal cortex and
      the ratio of free SA to bound SA in the hippocampus (p = 0.04). Diffusion tensor
      imaging indicated treatment effects in mean (p < 0.01), axial (p < 0.01) and
      radial (p = 0.01) diffusivity in the corpus callosum. Tract-based spatial
      statistics (TBSS) indicated differences (p < 0.05) in white matter tracts and
      voxel-based morphometry (VBM) indicated differences (p < 0.05) in grey matter
      between LOW and MOD pigs. CONT and HIGH pigs were not included in the TBSS and
      VBM assessments. These findings suggest the corpus callosum, prefrontal cortex
      and hippocampus may be differentially sensitive to dietary SL supplementation.

PMID- 29182579
TI  - Antarctic Krill Oil Diet Protects against Lipopolysaccharide-Induced Oxidative
      Stress, Neuroinflammation and Cognitive Impairment.
AB  - Oxidative stress and neuroinflammation are implicated in the development and
      pathogenesis of Alzheimer's disease (AD). Here, we investigated the anti
      inflammatory and antioxidative effects of krill oil. Oil from Euphausia superba
      (Antarctic krill), an Antarctic marine species, is rich in eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA). We examined whether krill oil diet (80
      mg/kg/day for one month) prevents amyloidogenesis and cognitive impairment
      induced by intraperitoneal lipopolysaccharide (LPS) (250 ug/kg, seven times
      daily) injections in AD mice model and found that krill oil treatment inhibited
      the LPS-induced memory loss. We also found that krill oil treatment inhibited the
      LPS-induced expression of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) and decreased reactive oxygen species (ROS) and
      malondialdehyde levels. Krill oil also suppresses IkappaB degradation as well as
      p50 and p65 translocation into the nuclei of LPS-injected mice brain cells. In
      association with the inhibitory effect on neuroinflammation and oxidative stress,
      krill oil suppressed amyloid beta (1-42) peptide generation by the down
      regulating APP and BACE1 expression in vivo. We found that eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) (50 and 100 uM) dose-dependently decreased
      LPS-induced nitric oxide and ROS generation, and COX-2 and iNOS expression as
      well as nuclear factor-kappaB activity in cultured microglial BV-2 cells. These
      results suggest that krill oil ameliorated impairment via anti-inflammatory,
      antioxidative, and anti-amyloidogenic mechanisms.

PMID- 29182580
TI  - Genes and Gut Bacteria Involved in Luminal Butyrate Reduction Caused by Diet and
      Loperamide.
AB  - Unbalanced dietary habits and gut dysmotility are causative factors in metabolic
      and functional gut disorders, including obesity, diabetes, and constipation.
      Reduction in luminal butyrate synthesis is known to be associated with gut
      dysbioses, and studies have suggested that restoring butyrate formation in the
      colon may improve gut health. In contrast, shifts in different types of gut
      microbiota may inhibit luminal butyrate synthesis, requiring different treatments
      to restore colonic bacterial butyrate synthesis. We investigated the influence of
      high-fat diets (HFD) and low-fiber diets (LFD), and loperamide (LPM)
      administration, on key bacteria and genes involved in reduction of butyrate
      synthesis in mice. MiSeq-based microbiota analysis and HiSeq-based differential
      gene analysis indicated that different types of bacteria and genes were involved
      in butyrate metabolism in each treatment. Dietary modulation depleted butyrate
      kinase and phosphate butyryl transferase by decreasing members of the
      Bacteroidales and Parabacteroides. The HFD also depleted genes involved in
      succinate synthesis by decreasing Lactobacillus. The LFD and LPM treatments
      depleted genes involved in crotonoyl-CoA synthesis by decreasing Roseburia and
      Oscilllibacter. Taken together, our results suggest that different types of
      bacteria and genes were involved in gut dysbiosis, and that selected treatments
      may be needed depending on the cause of gut dysfunction.

PMID- 29182581
TI  - Harvesting a 3D N-Doped Carbon Network from Waste Bean Dregs by Ionothermal
      Carbonization as an Electrocatalyst for an Oxygen Reduction Reaction.
AB  - Three-dimensional nitrogen-doped carbon (3D-NCN) has been synthesized via the
      ionothermal carbonization method using waste soybean dregs (SD) as the precursor.
      N2 adsorption/desorption isotherms show that the as-prepared 3D-NCN formed a
      hierarchically porous structure with a specific BET surface area of 1093.4 m2 g-1
      and a total pore volume of 1.77 cm3 g-1. The TEM images clearly show that
      graphene-like carbon sheets were formed on the edge of the networks. The
      characterization of the samples collected at different temperature indicated that
      salt melt plays the key role in the formation of the network structure and rich
      pores. When 3D-NCN is as electrocatalyst for ORR, it shows an onset potential of
      0.945 V with a more positive half-wave potential (0.846 V), which is comparable
      to that of commercial Pt/C. In addition, the long-term cycle results show that
      the onset potential and half-wave potential only negatively shifted by 6 mV and 8
      mV after 10,000 cycles respectively, which are smaller than those values of
      commercial Pt/C. Due to its high ORR activity, durability, and low-cost,
      producing 3D-NCN from SD in molten salt medium provides a promising approach to
      replace the Pt-based catalysts for use in fuel cells.

PMID- 29182582
TI  - New Half-Metallic Materials: FeRuCrP and FeRhCrP Quaternary Heusler Compounds.
AB  - The electronic structures and magnetic properties of FeRuCrP and FeRhCrP
      quaternary Heusler compounds with LiMgPbSb-type structures have been investigated
      via first-principles calculations. The calculational results show that both
      FeRuCrP and FeRhCrP compounds present perfect half-metallic properties: Showing
      large half-metallic band gaps of 0.39 eV and 0.38 eV, respectively. The total
      magnetic moments of FeRuCrP and FeRhCrP are 3 MUB and 4 MUB per formula unit,
      respectively. The magnetism of them mainly comes from the 3d electrons of Cr
      atoms and follows the Slater-Paulig behavior of Heusler compounds: Mt = Zt - 24.
      Furthermore, the half-metallic properties of FeRuCrP and FeRhCrP compounds can be
      kept in a quite large range of lattice constants (about 5.44-5.82 A and 5.26-5.86
      A, respectively) and are quite robust against tetragonal deformation (c/a ratio
      in the range of 0.94-1.1 and 0.97-1.1, respectively). Moreover, the large
      negative cohesion energy and formation energy of FeRuCrP and FeRhCrP compounds
      indicate that they can be synthesized experimentally.

PMID- 29182583
TI  - trans-Double Bond-Containing Liposomes as Potential Carriers for Drug Delivery.
AB  - The use of liposomes has been crucial for investigations in biomimetic chemical
      biology as a membrane model and in medicinal chemistry for drug delivery.
      Liposomes are made of phospholipids whose biophysical characteristics strongly
      depend on the type of fatty acid moiety, where natural unsaturated lipids always
      have the double bond geometry in the cis configuration. The influence of lipid
      double bond configuration had not been considered so far with respect to the
      competence of liposomes in delivery. We were interested in evaluating possible
      changes in the molecular properties induced by the conversion of the double bond
      from cis to trans geometry. Here we report on the effects of the addition of
      trans-phospholipids supplied in different amounts to other liposome constituents
      (cholesterol, neutral phospholipids and cationic surfactants), on the size, zeta
      potential and stability of liposomal formulations and on their ability to
      encapsulate two dyes such as rhodamine B and fluorescein. From a biotechnological
      point of view, trans-containing liposomes proved to have different
      characteristics from those containing the cis analogues, and to influence the
      incorporation and release of the dyes. These results open new perspectives in the
      use of the unnatural lipid geometry, for the purpose of changing liposome
      behavior and/or of obtaining molecular interferences, also in view of synergic
      effects of cell toxicity, especially in antitumoral strategies.

PMID- 29182584
TI  - Adjuvant Biological Therapies in Chronic Leg Ulcers.
AB  - Current biological treatments for non-healing wounds aim to address the common
      deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis
      and reduced synthesis of extracellular matrix. In this context, regenerative
      medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell
      products, may form part of adjuvant interventions in an integral patient
      management. We synthesized the clinical experience on ulcer management using
      these two categories of biological adjuvants. The results of ten controlled
      trials that are included in this systematic review favor the use of mesenchymal
      stromal cell based-adjuvants for impaired wound healing, but the number and
      quality of studies is moderate-low and are complicated by the diversity of
      biological products. Regarding platelet-derived products, 18 controlled studies
      investigated their efficacy in chronic wounds in the lower limb, but the
      heterogeneity of products and protocols hinders clinically meaningful
      quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical
      need in this condition. Overall, there is not sufficient evidence to inform
      routine care, and further clinical research is necessary to realize the full
      potential of adjuvant regenerative medicine strategies in the management of
      chronic leg ulcers.

PMID- 29182585
TI  - Optimization and Characterization of Paper-Made Surface Enhanced Raman Scattering
      (SERS) Substrates with Au and Ag NPs for Quantitative Analysis.
AB  - In this work, we present a systematic study on solid Surface Enhanced Raman
      Scattering (SERS) substrates consisting of Au and Ag nanoparticles (NPs) loaded
      on filter paper with the dip-coating method. The aim of this work is to explore
      how a series of parameters (e.g., concentration of colloidal solution, different
      porosity of filter paper, and the presence of an aggregating agent) affects the
      analytical performance of paper-based SERS substrates. All the substrates
      developed in this study have been analyzed with two non-resonant probe molecules,
      4-mercaptobenzoic acid (4-MBA) and adenine, in terms of (i) inter-sample
      repeatability, (ii) intra-sample repeatability, (iii) sensitivity, and (iv)
      overall SERS performance in terms of analyte quantification. Moreover, the issue
      of how to evaluate the repeatability for a solid SERS substrate is carefully
      discussed.

PMID- 29182586
TI  - Bioinspired versus Enzymatic Oxidation of Some Homologous Thionine Dyes in the
      Presence of Immobilized Metalloporphyrin Catalysts and Ligninolytic Enzymes.
AB  - Thionines are recalcitrant and polluting textile dyes presenting various degrees
      of N-methylation. In this paper, a complete series of homologous thionines was
      used as the substrates for oxidation in the presence of a bioinspired commercial
      iron-porphyrin immobilized on to imidazole- and pyridine-functionalized fumed
      silica, to emulate the active site of ligninolytic peroxidases. The obtained
      catalytic adducts showed a remarkable ability to catalyze thionine dye oxidation
      in the presence of different oxidants such as potassium monopersulfate and
      hydrogen peroxide. Different oxidation patterns were obtained and mechanistically
      discussed, in comparison with those observed in the presence of some ligninolytic
      oxidizing enzymes.

PMID- 29182589
TI  - Radio-Frequency-Controlled Urea Dosing for NH3-SCR Catalysts: NH3 Storage
      Influence to Catalyst Performance under Transient Conditions.
AB  - Current developments in exhaust gas aftertreatment led to a huge mistrust in
      diesel driven passenger cars due to their NOx emissions being too high. The
      selective catalytic reduction (SCR) with ammonia (NH3) as reducing agent is the
      only approach today with the capability to meet upcoming emission limits.
      Therefore, the radio-frequency-based (RF) catalyst state determination to monitor
      the NH3 loading on SCR catalysts has a huge potential in emission reduction.
      Recent work on this topic proved the basic capability of this technique under
      realistic conditions on an engine test bench. In these studies, an RF system
      calibration for the serial type SCR catalyst Cu-SSZ-13 was developed and
      different approaches for a temperature dependent NH3 storage were determined.
      This paper continues this work and uses a fully calibrated RF-SCR system under
      transient conditions to compare different directly measured and controlled NH3
      storage levels, and NH3 target curves. It could be clearly demonstrated that the
      right NH3 target curve, together with a direct control on the desired level by
      the RF system, is able to operate the SCR system with the maximum possible NOx
      conversion efficiency and without NH3 slip.

PMID- 29182588
TI  - Fluorinated Analog NMR s of Organosulfur Compounds from Garlic (Allium sativum):
      Synthesis, Chemistry and Anti-Angiogenesis and Antithrombotic Studies.
AB  - We describe the synthesis, reactivity, and antithrombotic and anti-angiogenesis
      activity of difluoroallicin (S-(2-fluoroallyl) 2-fluoroprop-2-ene-1
      sulfinothioate) and S-2-fluoro-2-propenyl-l-cysteine, both easily prepared from
      commercially available 3-chloro-2-fluoroprop-1-ene, as well as the synthesis of
      1,2-bis(2-fluoroallyl)disulfane, 5-fluoro-3-(1-fluorovinyl)-3,4-dihydro-1,2
      dithiin, trifluoroajoene ((E,Z)-1-(2-fluoro-3-((2-fluoroallyl)sulfinyl)prop-1-en
      1-yl)-2-(2-fluoroallyl)disulfane), and a bis(2-fluoroallyl)polysulfane mixture.
      All tested organosulfur compounds demonstrated effective inhibition of either FGF
      or VEG-mediated angiogenesis (anti-angiogenesis activity) in the chick
      chorioallantoic membrane (CAM) or the mouse Matrigel(r) models. No embryo
      mortality was observed. Difluoroallicin demonstrated greater inhibition (p <
      0.01) versus organosulfur compounds tested. Difluoroallicin demonstrated dose
      dependent inhibition of angiogenesis in the mouse Matrigel(r) model, with maximal
      inhibition at 0.01 mg/implant. Allicin and difluoroallicin showed an effective
      antiplatelet effect in suppressing platelet aggregation compared to other
      organosulfur compounds tested. In platelet/fibrin clotting (anti-coagulant
      activity), difluoroallicin showed concentration-dependent inhibition of clot
      strength compared to allicin and the other organosulfur compounds tested.

PMID- 29182587
TI  - Recent Advances in Momordica charantia: Functional Components and Biological
      Activities.
AB  - Momordica charantia L. (M. charantia), a member of the Cucurbitaceae family, is
      widely distributed in tropical and subtropical regions of the world. It has been
      used in folk medicine for the treatment of diabetes mellitus, and its fruit has
      been used as a vegetable for thousands of years. Phytochemicals including
      proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and
      steroids have been found in this plant. Various biological activities of M.
      charantia have been reported, such as antihyperglycemic, antibacterial,
      antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic,
      antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective,
      anticancer and anti-inflammatory activities. However, both in vitro and in vivo
      studies have also demonstrated that M. charantia may also exert toxic or adverse
      effects under different conditions. This review addresses the chemical
      constituents of M. charantia and discusses their pharmacological activities as
      well as their adverse effects, aimed at providing a comprehensive overview of the
      phytochemistry and biological activities of M. charantia.

PMID- 29182591
TI  - ECG Signal De-noising and Baseline Wander Correction Based on CEEMDAN and Wavelet
      Threshold.
AB  - A novel electrocardiogram (ECG) signal de-noising and baseline wander correction
      method based on complete ensemble empirical mode decomposition with adaptive
      noise (CEEMDAN) and wavelet threshold is proposed. Although CEEMDAN is based on
      empirical mode decomposition (EMD), it represents a significant improvement of
      the original EMD by overcoming the mode-mixing problem. However, there has been
      no previous study on using CEEMDAN to de-noise ECG signals, to the authors' best
      knowledge. In the proposed method, the original noisy ECG signal is decomposed
      into a series of intrinsic mode functions (IMFs) sorted from high to low
      frequency by CEEMDAN. Each IMF is then analyzed by the autocorrelation method to
      find out the first few high frequency IMFs containing random noise, and these
      IMFs should be de-noised by the wavelet threshold. The zero-crossing rate (ZCR)
      of all IMFs, including final residue, are computed, and the IMFs with ZCR less
      than a certain value are removed. Finally, the remaining IMFs are reconstructed
      to obtain the clean ECG signal. The proposed algorithm is validated through
      experiments using the MIT-BIH ECG databases, and the results show that the random
      noise in the ECG signal can be effectively suppressed, and at the same time the
      baseline wander can be corrected efficiently.

PMID- 29182590
TI  - Study on the Prevalence of Severe Anemia among Non-Pregnant Women of Reproductive
      Age in Rural China: A Large Population-Based Cross-Sectional Study.
AB  - Globally, severe anemia impacts millions of non-pregnant women. However, studies
      on the prevalence of severe anemia through large epidemiologic surveys among non
      pregnant women have been scarce in China. In this study, we aimed to study the
      prevalence of severe anemia and its determinants among non-pregnant women living
      in rural areas of China. Data were gathered for 712,101 non-pregnant women aged
      between 21 and 49 years who attended the 2012 National Free Preconception Health
      Examination Project. Severe anemia in non-pregnant women was defined as a
      hemoglobin (Hb) concentration lower than 80 g/L. Associated factors were analyzed
      using univariate and multivariate logistic regression methods. Out of the 712,101
      non-pregnant women living in the rural areas of China, 1728 suffered from severe
      anemia, with a prevalence of 0.24% (95% confidence interval (CI): 0.23-0.25%).
      Results from the multivariable logistic regression showed that elderly (adjusted
      odds ratio (aOR) = 3.08), living in the northwest region (aOR = 2.88), having a
      history of anemia (aOR = 5.76), with heavy menstrual blood loss (aOR = 1.84), and
      with a history of using an intra-uterine device (aOR = 1.47) etc., were
      independent determinants for women with severe anemia in rural China. The
      prevalence of severe anemia among Chinese non-pregnant women living in the rural
      areas was lower than the reported global prevalence. Prevention and intervention
      programs for severe anemia are required among non-pregnant women of reproductive
      age in the rural areas of China.

PMID- 29182592
TI  - A Novel Adaptive Hinfinity Filtering Method with Delay Compensation for the
      Transfer Alignment of Strapdown Inertial Navigation Systems.
AB  - Transfer alignment is always a key technology in a strapdown inertial navigation
      system (SINS) because of its rapidity and accuracy. In this paper a transfer
      alignment model is established, which contains the SINS error model and the
      measurement model. The time delay in the process of transfer alignment is
      analyzed, and an Hinfinity filtering method with delay compensation is presented.
      Then the Hinfinity filtering theory and the robust mechanism of Hinfinity filter
      are deduced and analyzed in detail. In order to improve the transfer alignment
      accuracy in SINS with time delay, an adaptive Hinfinity filtering method with
      delay compensation is proposed. Since the robustness factor plays an important
      role in the filtering process and has effect on the filtering accuracy, the
      adaptive Hinfinity filter with delay compensation can adjust the value of
      robustness factor adaptively according to the dynamic external environment. The
      vehicle transfer alignment experiment indicates that by using the adaptive
      Hinfinity filtering method with delay compensation, the transfer alignment
      accuracy and the pure inertial navigation accuracy can be dramatically improved,
      which demonstrates the superiority of the proposed filtering method.

PMID- 29182593
TI  - Analytical Methods of Phytochemicals from the Genus Gentiana.
AB  - The genus Gentiana comprises approximately 400 species. Many species have a wide
      range of pharmacological activities and have been used therapeutically for
      thousands of years. To provide comprehensive guidance, utilization and quality
      control of Gentiana species, this review presents updated information concerning
      the recent application and progress of chemical analysis including phytochemical
      analysis, sample preparation and chemometrics. Detailed and comprehensive data
      including number of analytes, extraction/separation methods, analytical
      techniques and chemometrics are shown as corresponding tables. These data
      illustrate that the development of newly discovered compounds and therapeutic
      uses, understanding of the structure-activity relationship and establishment of
      harmonious and effective medicinal herb standards are the direction of
      advancement in future research.

PMID- 29182595
TI  - Identifying Patients Who Will Most Benefit from Single Photon Emission
      Computerized Tomography and Computerized Tomography After Femoral Neck Fracture.
AB  - BACKGROUND Single photon emission computerized tomography and computerized
      tomography (SPECT/CT) is useful for assessing blood supply within the femoral
      head after femoral neck fracture, but its use in all femoral neck fracture
      patients is not feasible. Therefore, the present study aimed to identify the
      patients for whom SPECT/CT examination will be most beneficial. MATERIAL AND
      METHODS Sixty-five patients with a unilateral femoral neck fracture who underwent
      SPECT/CT examination of the hip and were treated via closed reduction and
      internal fixation with three screws were enrolled between January 2009 and March
      2011. A decision tree model (C 5.0) was used to identify the factors that best
      reflect blood supply and to build a flowchart for identifying patients who would
      benefit from SPECT/CT. RESULTS Fracture type was most strongly associated with
      the Fracture/Normal (F/N) ratio, which reflects the blood supply to the fractured
      femoral head. Age and the time interval from injury to examination were also
      associated with the F/N ratio. SPECT/CT examination is most beneficial for
      patients with a displaced fracture, especially if they are over 58 years old and
      the time interval from injury to examination is less than 10 days. CONCLUSIONS
      Our results indicate that elderly people with a displaced fracture are most
      likely to benefit from SPECT/CT examination, which can show the blood supply to
      the femoral head within a relatively short window of time after the injury.

PMID- 29182594
TI  - Pharmacokinetics of Chlorin e6-Cobalt Bis(Dicarbollide) Conjugate in Balb/c Mice
      with Engrafted Carcinoma.
AB  - The necessary precondition for efficient boron neutron capture therapy (BNCT) is
      control over the content of isotope 10B in the tumor and normal tissues. In the
      case of boron-containing porphyrins, the fluorescent part of molecule can be used
      for quantitative assessment of the boron content. Study Objective: We performed a
      study of the biodistribution of the chlorin e6-Cobalt bis(dicarbollide) conjugate
      in carcinoma-bearing Balb/c mice using ex vivo fluorescence imaging, and
      developed a mathematical model describing boron accumulation and release based on
      the obtained experimental data. Materials and Methods: The study was performed on
      Balb/c tumor-bearing mice (CT-26 tumor model). A solution of the chlorin e6
      Cobalt bis(dicarbollide) conjugate (CCDC) was injected into the blood at a dose
      of 10 mg/kg of the animal's weight. Analysis of the fluorescence signal intensity
      was performed at several time points by spectrofluorimetry in blood and by laser
      scanning microscopy in muscle, liver, and tumor tissues. The boron content in the
      same samples was determined by mass spectroscopy with inductively coupled plasma.
      Results: Analysis of a linear approximation between the fluorescence intensity
      and boron content in the tissues demonstrated a satisfactory value of
      approximation reliability with a Spearman's rank correlation coefficient of r =
      0.938, p < 0.01. The dynamics of the boron concentration change in various
      organs, calculated on the basis of the fluorescence intensity, enabled the
      development of a model describing the accumulation of the studied compound and
      its distribution in tissues. The obtained results reveal a high level of
      correspondence between the model and experimental data.

PMID- 29182596
TI  - [Comparability of the editions 2006/07 and 2011/12 of the Spanish Health Survey.]
AB  - OBJECTIVE: The Spanish Health Survey (SHS) is one of the main sources on social
      determinants of health. The objectives were to describe the data merging process
      of the 2006/07 and 2011/12 SHS editions, as well as to provide the merged
      databases and the directory of the variables. METHODS: The comparable variables
      were identified from the questionnaires. Other new variables were created to
      achieve comparability or to provide new indicators of interest. We obtained two
      completed merged databases, as well as two variable directories with their
      dictionaries (each one for the adults and children samples). RESULTS: 188
      variables were identified as potentially comparable ones. 36,7% of them had
      difficulties for being comparable and 8% had to be removed. The topic with the
      worst consequences due to the lack of comparability was the working conditions
      and employment from the adult sample. CONCLUSIONS: The merging of both SHS
      editions had a lot of problems, especially in the adult's sample. That affects to
      its comparability. This work may be useful to assess, design and merge these and
      other editions of the SHS, as well as to serve as a model to be applied in other
      cross-sectional population-based surveys.

PMID- 29182597
TI  - [Epidemiology of Imperfect Osteogenesis: a Rare Disease in the Valencia Region.]
AB  - OBJECTIVE: Osteogenesis imperfecta (OI) is a rare connective tissue and bone
      disease that results in a bone fragility of varying severity. The objective was
      to determine and describe the OI in the Valencia Region (VR) during the period
      2004 to 2014. METHODS: From the Rare Diseases Information System of the VR (SIER
      CV) patients from 2004 to 2014 with the codes of the International Classification
      of Diseases for the OI were identified: 756.51 from the 9th Revision-Clinical
      Modification and Q78.0 from the 10th Revision. The information was validated by
      reviewing clinical documentation (mainly electronic health records) and a
      descriptive analysis of the confirmed cases (diagnosis of OI in the clinical
      documentation) was performed. RESULTS: 162 patients were identified with a code
      for OI. 145 of the 161 patients with available clinical documentation were
      confirmed as cases. The prevalence was 0.29 per 10.000 inhabitants. 93.1% were
      Spanish, 54.5% were women and they were treated in 25 different hospitals in the
      VR. The type of OI was known in the 26.4% of the cases and type I was the most
      common (9.7%). 6.2% of the patients died with an average death age of 60.8 years.
      44.8% of patients received treatment with bisphosphonates and 10.4% had affected
      relatives. CONCLUSIONS: The real situation of the OI in the VR has been
      established, which will allow a better planning in the health actions to improve
      the quality of life of the affected ones and their families.

PMID- 29182599
TI  - Open University Learning Analytics dataset.
AB  - Learning Analytics focuses on the collection and analysis of learners' data to
      improve their learning experience by providing informed guidance and to optimise
      learning materials. To support the research in this area we have developed a
      dataset, containing data from courses presented at the Open University (OU). What
      makes the dataset unique is the fact that it contains demographic data together
      with aggregated clickstream data of students' interactions in the Virtual
      Learning Environment (VLE). This enables the analysis of student behaviour,
      represented by their actions. The dataset contains the information about 22
      courses, 32,593 students, their assessment results, and logs of their
      interactions with the VLE represented by daily summaries of student clicks
      (10,655,280 entries). The dataset is freely available at
      https://analyse.kmi.open.ac.uk/open_dataset under a CC-BY 4.0 license.

PMID- 29182598
TI  - Monitoring transcription initiation activities in rat and dog.
AB  - The promoter landscape of several non-human model organisms is far from complete.
      As a part of FANTOM5 data collection, we generated 13 profiles of transcription
      initiation activities in dog and rat aortic smooth muscle cells, mesenchymal stem
      cells and hepatocytes by employing CAGE (Cap Analysis of Gene Expression)
      technology combined with single molecule sequencing. Our analyses show that the
      CAGE profiles recapitulate known transcription start sites (TSSs) consistently,
      in addition to uncover novel TSSs. Our dataset can be thus used with high
      confidence to support gene annotation in dog and rat species. We identified
      28,497 and 23,147 CAGE peaks, or promoter regions, for rat and dog respectively,
      and associated them to known genes. This approach could be seen as a standard
      method for improvement of existing gene models, as well as discovery of novel
      genes. Given that the FANTOM5 data collection includes dog and rat matched cell
      types in human and mouse as well, this data would also be useful for cross
      species studies.

PMID- 29182600
TI  - RE-Europe, a large-scale dataset for modeling a highly renewable European
      electricity system.
AB  - Future highly renewable energy systems will couple to complex weather and climate
      dynamics. This coupling is generally not captured in detail by the open models
      developed in the power and energy system communities, where such open models
      exist. To enable modeling such a future energy system, we describe a dedicated
      large-scale dataset for a renewable electric power system. The dataset combines a
      transmission network model, as well as information for generation and demand.
      Generation includes conventional generators with their technical and economic
      characteristics, as well as weather-driven forecasts and corresponding
      realizations for renewable energy generation for a period of 3 years. These may
      be scaled according to the envisioned degrees of renewable penetration in a
      future European energy system. The spatial coverage, completeness and resolution
      of this dataset, open the door to the evaluation, scaling analysis and
      replicability check of a wealth of proposals in, e.g., market design, network
      actor coordination and forecasting of renewable power generation.

PMID- 29182601
TI  - Perspective on Diamond-Blackfan anemia: lessons from a rare congenital bone
      marrow failure syndrome.

PMID- 29182602
TI  - UTUC in 2017: Emerging evidence on treating upper tract urothelial cancer.

PMID- 29182604
TI  - Prostate cancer: H2A.Zac activates neo-enhancers.

PMID- 29182605
TI  - Prostate cancer: Glycolysis and AR expression as biomarkers.

PMID- 29182606
TI  - Bladder cancer in 2017: Advancing care through genomics and immune checkpoint
      blockade.

PMID- 29182603
TI  - A psychosocial approach to female genital pain.
AB  - Genital pain is a prevalent, complex, and disabling health concern in women.
      Efforts to study this chronic pain condition have been complicated by the fact
      that genital pain is heterogeneous and exists at the intersection of different
      biopsychosocial disciplines. Thus, organization of theoretical ideas and
      empirical findings across research areas is required to improve our understanding
      of how biopsychosocial factors affect the development and maintenance of the
      pain, the reporting of symptoms, and the choice of treatment. In the past, the
      study of physical markers has received the most research attention; an
      assimilation of the psychosocial variables underlying genital pain is, therefore,
      particularly needed to inform the field about the rapidly growing literature and
      stimulate interdisciplinary work. Current research lacks specificity, fails to
      capture the unique features of different pain conditions, and yields conflicting
      evidence, which makes it difficult to draw uniform conclusions. Although
      considerable advances have been made, confusion remains at the nosological,
      aetiological, theoretical, methodological, and treatment levels. This lack of
      consensus has important theoretical and clinical implications because
      inconsistent criteria and empirical disagreement can lead to misdiagnoses and
      interfere with the development of sound theoretical models and effective
      treatments to manage female genital pain and its physical and psychological
      sequelae.

PMID- 29182607
TI  - The current state of funded NIH grants in implementation science in genomic
      medicine: a portfolio analysis.
AB  - PurposeImplementation science offers methods to evaluate the translation of
      genomic medicine research into practice. The extent to which the National
      Institutes of Health (NIH) human genomics grant portfolio includes implementation
      science is unknown. This brief report's objective is to describe recently funded
      implementation science studies in genomic medicine in the NIH grant portfolio,
      and identify remaining gaps.MethodsWe identified investigator-initiated NIH
      research grants on implementation science in genomic medicine (funding initiated
      2012-2016). A codebook was adapted from the literature, three authors coded
      grants, and descriptive statistics were calculated for each code.ResultsForty-two
      grants fit the inclusion criteria (~1.75% of investigator-initiated genomics
      grants). The majority of included grants proposed qualitative and/or quantitative
      methods with cross-sectional study designs, and described clinical settings and
      primarily white, non-Hispanic study populations. Most grants were in oncology and
      examined genetic testing for risk assessment. Finally, grants lacked the use of
      implementation science frameworks, and most examined uptake of genomic medicine
      and/or assessed patient-centeredness.ConclusionWe identified large gaps in
      implementation science studies in genomic medicine in the funded NIH portfolio
      over the past 5 years. To move the genomics field forward, investigator-initiated
      research grants should employ rigorous implementation science methods within
      diverse settings and populations.Genetics in Medicine advance online publication,
      26 October 2017; doi:10.1038/gim.2017.180.

PMID- 29182608
TI  - Impact of tumour histology on survival in advanced cervical carcinoma: an NRG
      Oncology/Gynaecologic Oncology Group Study.
AB  - BACKGROUND: Based primarily on studies concerning early-stage tumours (treated
      surgically), and locally advanced disease (treated with chemoradiation), the
      prognosis for women with adenocarcinoma (AC) or adenosquamous (AS) carcinoma has
      been reported to be poorer than those with squamous cell carcinoma (SCCA) of the
      cervix. It is unclear whether differences in prognosis also persist in the
      setting of recurrent or metastatic disease treated using chemotherapy doublets
      with or without bevacizumab. METHODS: Cases were pooled from three Gynaecologic
      Oncology Group randomised phase III trials of chemotherapy doublets. Pearson's
      test was used to evaluate response rate (RR) of AC/AS vs SCCA, Kaplan-Meier
      method to estimate progression-free survival (PFS) and overall survival (OS), and
      Cox proportional hazards model to estimate the impact of histology on PFS and OS.
      RESULTS: Of 781 evaluable patients, 77% (N=599) had SCCA and 23% (N=182) AC/AS.
      There were no significant differences in RRs between histologic subgroups. The
      adjusted hazard ratio (HR) for death for SCCA vs AC/AS was 1.13 (95% CI 0.93,
      1.38 P=0.23). When comparing SC/AS (N=661, 85%) to AC alone (N=120, 15%), the
      adjusted HR for death was 1.23 (95% CI 0.97, 1.57, P=0.09). CONCLUSIONS: AC/AS
      and SCCA have similar survival in recurrent or metastatic cervical carcinoma when
      treated with chemotherapy doublets.

PMID- 29182610
TI  - BDNF expression in cat striate cortex is regulated by binocular pattern
      deprivation.
AB  - Deprivation of patterned visual information, as in early onset congenital
      cataract patients, results in a severe impairment in global motion perception.
      Previously we reported a delayed maturation of the peripheral visual field
      representation in primary visual area 17, based on a 2-D DIGE screen for protein
      expression changes and in situ hybridization for the activity reporter gene
      ZIF268. To corroborate these findings we here explore the binocular pattern
      deprivation (BD)-regulated expression of brain-derived neurotrophic factor
      (BDNF), a well-described neurotrophin precipitously regulated by early visual
      experience. To assess the timing of maturation-related BDNF expression we
      compared the central and the peripheral visual field representations of area 17
      of 1, 2, 4 and 6-month-old and adult cats reared under normal visual conditions.
      To scrutinize the outcome of BD, four different deprivation strategies were
      compared, including early onset BD from birth and lasting for 2, 4 or 6 months
      (2BD, 4BD, 6BD), and late onset BD for 2 months upon 2 months of normal vision
      (2N2BD), as animal models of congenital and delayed onset cataract. During normal
      cortical development the BDNF transcript levels, measured by quantitative RT-PCR,
      remained stable. Higher BDNF mRNA levels were found in central area 17 of 2BD and
      6BD animals compared to age-matched controls. In central area 17, the high BDNF
      mRNA levels at the end of the BD period may activate a mechanism by which plastic
      processes, halted by deprivation, may begin. We here confirm that the peripheral
      visual field representation of area 17 matures slower than its central
      counterpart. Only in central area 17 normal visual input upon BD could upregulate
      BDNF mRNA which may lead to a fast activation of local plastic adaptations.

PMID- 29182609
TI  - Variation in 'fast-track' referrals for suspected cancer by patient
      characteristic and cancer diagnosis: evidence from 670 000 patients with cancers
      of 35 different sites.
AB  - BACKGROUND: In England, 'fast-track' (also known as 'two-week wait') general
      practitioner referrals for suspected cancer in symptomatic patients are used to
      shorten diagnostic intervals and are supported by clinical guidelines. However,
      the use of the fast-track pathway may vary for different patient groups. METHODS:
      We examined data from 669 220 patients with 35 cancers diagnosed in 2006-2010
      following either fast-track or 'routine' primary-to-secondary care referrals
      using 'Routes to Diagnosis' data. We estimated the proportion of fast-track
      referrals by sociodemographic characteristic and cancer site and used logistic
      regression to estimate respective crude and adjusted odds ratios. We additionally
      explored whether sociodemographic associations varied by cancer. RESULTS: There
      were large variations in the odds of fast-track referral by cancer (P<0.001).
      Patients with testicular and breast cancer were most likely to have been
      diagnosed after a fast-track referral (adjusted odds ratios 2.73 and 2.35,
      respectively, using rectal cancer as reference); whereas patients with brain
      cancer and leukaemias least likely (adjusted odds ratios 0.05 and 0.09,
      respectively, for brain cancer and acute myeloid leukaemia). There were sex, age
      and deprivation differences in the odds of fast-track referral (P<0.013) that
      varied in their size and direction for patients with different cancers (P<0.001).
      For example, fast-track referrals were least likely in younger women with
      endometrial cancer and in older men with testicular cancer. CONCLUSIONS: Fast
      track referrals are less likely for cancers characterised by nonspecific
      presenting symptoms and patients belonging to low cancer incidence demographic
      groups. Interventions beyond clinical guidelines for 'alarm' symptoms are needed
      to improve diagnostic timeliness.

PMID- 29182611
TI  - The differential effects of neuroleptic drugs and PACAP on the expression of BDNF
      mRNA and protein in a human glioblastoma cell line.
AB  - Despite numerous studies, the molecular mechanisms underpinning the action of
      antipsychotic drugs remain not fully understood. It has been suggested that, in
      addition to the modulation of monoaminergic neurotransmission, antipsychotic
      drugs can also affect the expression of neurotrophic factors in the brain. The
      present study examines the effects of a first-generation neuroleptic drug (FGA;
      haloperidol) and two second-generation neuroleptic drugs (SGAs; olanzapine and
      amisulpride) on the expression and levels of brain-derived neurotrophic factor
      (BDNF) in an astrocyte-like T98G glioblastoma cell line. The effects of these
      drugs were compared to the action of PACAP38, a neuropeptide with well-known BDNF
      mediated neuroprotective effects. The tested neuroleptics differentially
      regulated the mRNA expression and protein level of BDNF depending on
      concentration and incubation time. Real-time PCR analysis demonstrates that, of
      the three tested neuroleptics, both haloperidol and olanzapine at a concentration
      of 5 uM (but not at 20 uM) increased BDNF mRNA expression with similar efficacy
      after 72-hour incubation. In order to confirm the observed changes in the mRNA
      expression of BDNF, a protein expression assay was performed. The exposure of
      cells to 5 MUM olanzapine alone for 72 hours increased BDNF concentration in the
      culture medium by 29%. Additionally, PACAP significantly up-regulated BDNF mRNA
      expression in T98G cells and the obtained results correlated positively with the
      increased production of BDNF protein, 22% above control values. Our findings show
      that olanzapine, similarly to exogenous PACAP38, increased BDNF mRNA expression
      and protein release, which can contribute to its neuroprotective mechanism of
      action in the cells of non-neuronal origin. The results of the paper show that
      olanzapine, similarly to exogenous PACAP38, increased BDNF mRNA expression and
      protein release, which can contribute to its neuroprotective mechanism of action
      in the cells of nonneuronal origin. The results of the present paper confirm the
      findings that BDNF may represent the key target for olanzapine and PACAP.

PMID- 29182612
TI  - Nucleus accumbens local field potential power spectrums, phase-amplitude
      couplings and coherences following morphine treatment.
AB  - In the past decade, neural processing has been extensively studied in cognitive
      neuroscience. However, neural signaling in the nucleus accumbens (NAc) that might
      clarify reward process remained to be investigated. Male Swiss albino ICR mice
      implanted with intracranial electrodes into the NAc and the ventral tegmental
      area (VTA) were used for morphine administration and local field potential (LFP)
      recording. One-way ANOVA revealed significant increases in low (30.3-44.9 Hz) and
      high (60.5-95.7 Hz) gamma powers in the NAc following morphine administration (5
      and 15 mg/kg, i.p.). These gamma activities oscillated independently with
      different time-course responses. Locomotor activity was also significantly
      increased by morphine administration. Regression analyses revealed that high
      gamma activity induced by morphine was positively correlated with distance
      travelled by animals. Low and high gamma powers were completely abolished by
      injection of naloxone, a non-specific opiate antagonist. Analysis of phase
      amplitude coupling confirmed that slow oscillations at 1-4 Hz (delta) and 4-8 Hz
      (theta) for phase were found to significantly increase modulation index of broad
      (30.27-80.77 Hz) and narrow (59.48-70.34 Hz) frequency ranges for amplitude,
      respectively. Moreover, significant increases in coherence values between the NAc
      and the VTA during 30-40 min following morphine administration were seen for
      22.46-44.90 Hz frequency range. Altogether, this study demonstrated changes of
      LFP oscillations in the NAc with low and high gamma activities, delta- and theta
      gamma couplings and interplay with VTA in response to morphine administration.
      These findings represent neural signaling in the mesolimbic dopamine pathway that
      might process reward function.

PMID- 29182613
TI  - Assessment of type 1 and type 3 deiodinase expression levels in depressive
      disorders.
AB  - A depressive disorder is a disease characterized by a heterogenous background.
      The important processes observed and diagnosed in depressed patients indicate
      that the etiology of depression may include disturbances in thyroid hormone (TH)
      levels and the occurrence of immune-inflammatory activation. Type 1 (DIO1) and
      type 3 (DIO3) iodothyronine deiodinases are the enzymes which determine the
      peripheral and tissue levels of TH, but also interfere with immunological cells
      and inflammatory processes. We aimed to investigate the levels of DIO1 and DIO3
      in the patients suffering from recurrent depressive disorders (rDD). Data
      collected from 91 rDD patients and 105 healthy controls were analyzed. The
      diagnoses were made based on the ICD-10 criteria (F33.0-F33.8). The expression
      levels of DIO1 and DIO3 were estimated using the polymerase chain reaction method
      and the enzyme-linked immunosorbent assay (ELISA). The expression of DIO1 on
      mRNA/protein levels in the rDD patients was reduced in comparison to the control
      subjects, while the expression of DIO3 was higher in the patients suffering from
      depression. No significant relationship was found between the investigated DIOs
      and other clinical parameters. Our results indicate and suggest a role of DIO1
      and DIO3-related pathways in the pathophysiology of depression. The results
      represent a promising way to investigate the biological markers of depression.

PMID- 29182614
TI  - Tiapride prevents the aversive but not the rewarding effect induced by
      parabrachial electrical stimulation in a place preference task.
AB  - The parabrachial complex has been related to the processing of both rewarding and
      aversive signals. This pontine area is activated after the gastrointestinal
      administration of rewarding nutrients, in taste aversion learning, and in
      response to the reinforcing and aversive effects of some drugs of abuse.
      Electrical stimulation of this region can induce, in different animals,
      preference or aversion behaviors towards a place in a rectangular three-chamber
      maze task. This study examined the effect of tiapride, a D2/D3 receptor
      antagonist, on the aversive or rewarding effects induced by electrical
      stimulation of the external lateral parabrachial subnucleus (NLPBe). As
      previously observed, administration of tiapride interrupted the aversive effect
      induced by NLPBe electrical stimulation. However, in contrast to the effects of
      dopamine antagonists on other rewarding systems, tiapride did not impair the
      place preference induced by NLPBe stimulation, an activation effect that is
      subject to tolerance. Tiapride administration also appeared to have no effect on
      the horizontal motor activity (crossings) of the electrically stimulated animals.
      We discuss the specific relevance of parabrachial reward with respect to other
      reinforcing brain components or systems, especially in relation to the preference
      effect of drugs of abuse, such as opiates, after dopamine antagonist
      administration.

PMID- 29182615
TI  - Effects of individual stressors used in a battery of "chronic unpredictable
      stress" on long-term plasticity in the hippocampus of juvenile rats.
AB  - We have studied alterations in the properties of long-term potentiation (LTP) in
      hippocampal slices of juvenile rats induced by the exposure of animals to
      different individual stressors usually used in batteries of chronic unpredictable
      stress (CUS), a widely used model of depression. Social isolation for 16 h did
      substantially affect neither the magnitude and nor the development of LTP. The
      effects of stroboscopic illumination and water deprivation appeared most severe,
      though opposite: the first stressor had activating effect, whereas the second one
      inhibited the development of LTP. In addition to the effects of these factors on
      the LTP magnitude, they also affected the patterns of LTP development. In this
      study weak tetanization with different probability of maintenance was used, and
      most of stressors, in spite of the similar LTP magnitude, influenced
      significantly on the process of consolidation. In hippocampal slices from rats
      maintained on wet bedding for 16 h, the time course but not magnitude of LTP
      significantly differed from that observed in the control or socially isolated
      rats. The weakest effect on LTP was observed in hippocampal slices of the rats
      exposed to food deprivation. In these animals, only some differences were
      observed in the development of LTP as compared to socially isolated rats. These
      data allow ranging stressors used in CUS paradigms according to the severity of
      their potential effects on neuronal function and animal behavior.

PMID- 29182616
TI  - Marble burying as compulsive behaviors in male and female mice.
AB  - Marble burying is considered an, albeit controversial, animal model of the
      compulsive like behaviors of obsessive-compulsive disorder (OCD). Hallmark
      features of OCD patients are similarities and, more prominent, differences from
      anxiety disorders, e.g., the absence of sex differences and resistance to
      spontaneous remission. We report an experiment on marble burying by male and
      female C57/BL6/N mice. Animals were administered either the classic anxiolytic
      drug, diazepam, that targets the GABA receptor or a "pure" inhibitor of the
      serotonin transporter, escitalopram, that has been reported to be particularly
      effective in OCD. A burying paradigm that more precisely mimics the human
      condition was used, e.g., testing in the home environment, chronic drug exposure
      and acknowledging individual differences by pre-selecting for high marble
      burying. Results were that there were no sex differences in groups treated with
      drugs or in control mice. Both diazepam and escitalopram decreased numbers of
      marbles buried compared to vehicle-only controls in the absence of correlated
      changes in anxiety. Diazepam, however, was more effective than escitalopram in
      suppressing MB. The conclusion is that along with serotonin, GABA is involved in
      regulating compulsive behaviors. The marble burying paradigm may prove more
      useful for pharmacological drugs tests of impulsivity or attention deficit
      because of the involvement of serotonin and GABA in both disorders.

PMID- 29182617
TI  - In vivo stimulation of locus coeruleus: effects on amygdala subnuclei.
AB  - The locus coeruleus (LC) is the major noradrenergic nucleus and sends projections
      to almost all brain areas. A marked increase in norepinephrine release has been
      demonstrated in several brain areas in response to exposure to acute stressful
      stimuli, especially those innervated by LC projections. One of the brain areas
      innervated by LC neurons is the amygdala, a structure highly involved in
      emotional processes and memory formation. The aim of this study was to increase
      knowledge of the functional connectivity between the LC and the amygdala
      subnuclei. To reach this objective, we evaluated c-fos immunoreactive cells in
      amygdala nuclei following direct electrical stimulation of the LC in conscious
      animals. This analysis of c-Fos immunoreactivity could inform whether there are
      differences in activity of the amygdala subnuclei related to LC electrical
      stimulation in conscious animals. Our results showed a marked increase in c-fos
      activity in these amygdala subnuclei both ipsilateral and contralateral to LC
      electrical stimulation in vivo. Therefore, our study provides evidence that in
      vivo electrical stimulation of LC is able to activate the amygdala subnuclei as
      measured by c-fos expression.

PMID- 29182618
TI  - Impact of scale of aggregation on associations of cardiovascular hospitalization
      and socio-economic disadvantage.
AB  - BACKGROUND: There are numerous studies that show an increased incidence of
      cardiovascular disease with increasing levels of socio-economic disadvantage.
      Exposures that might influence the relationship include elements of the built
      environment and social systems that shape lifestyle risk behaviors. In Canberra
      (the Australian capital city) there has been a particular housing policy to
      create 'mixed-tenure' neighborhoods so that small pockets of disadvantage are
      surrounded by more affluent residences (known as a 'salt-and-pepper' pattern).
      This may contribute to a scatter of higher incidence rates in very small areas in
      this population that may be obscured if aggregated data are used. This study
      explored the effect of changing the scale of the spatial units used in small area
      disease modelling, aiming to understand the impact of this issue and the
      implications for local public health surveillance. METHODS: The residence
      location of hospitalized individuals were aggregated to two differently scaled
      area units. First, the Australian Bureau of Statistics Statistical Area 2 (SA2)
      which is normally used as the basis for deidentification and release of health
      data. Second, these data were aggregated to a smaller level: the Statistical Area
      1 (SA1). Generalized Additive Models with penalized regression splines were used
      to assess the association of age-sex-standardized rates for cardiovascular
      disease hospital admissions with disadvantage. RESULTS: The relationships
      observed were different between the two types of spatial units. The SA1 level
      exposure-response curve for rates against the disadvantage index extended in a
      linear fashion above the midrange level, while that found at SA2-level suggested
      a curvilinear form with no evidence that rates increased with higher disadvantage
      beyond the midrange. CONCLUSION: Our result supports findings of other work that
      has found disadvantage increases risk of cardiovascular disease. The shape of the
      curves suggest a difference in associations of cardiovascular disease rates with
      disadvantage scores between SA1 versus SA2. From these results it can be
      concluded that scale of analysis does influence the understanding of geographical
      patterns of socio-economic disadvantage and cardiovascular disease morbidity.
      Health surveillance and interventions in Canberra should take into account the
      impact of the scale of aggregation on the association between disadvantage and
      cardiovascular disease observed.

PMID- 29182619
TI  - Response of imported malaria patients to antimalarial medicines in Sri Lanka
      following malaria elimination.
AB  - After eliminating local malaria transmission and being certified as a malaria
      free country, Sri Lanka is facing the challenge of imported malaria. At the same
      time, the country has the unique opportunity to be a case study for other
      countries in a similar situation by approaching this issue systematically, guided
      by evidence. This study demonstrates the importance of developing a mechanism to
      detect imported malaria and adopting an evidence-based approach to study the
      resistance of imported malaria to anti-malarial medicines. This is a prospective
      study of patients diagnosed with imported malaria in Sri Lanka and treated
      according to the national treatment guidelines, over 24 months (2015/2016). The
      clinical features, time to diagnosis, origin of the infection, infecting species,
      parasite density and the treatment given were recorded. All patients were
      followed up for 28 days, and in the case of Plasmodium vivax and P. ovale
      infections, the follow up period was extended to 12 months to establish treatment
      failures and relapses. Fifty nine uncomplicated and 15 severe imported malaria
      cases were reported in Sri Lanka during the study period. Most of these
      infections originated in either Sub-Saharan Africa or South and Southeast Asia.
      Having a P. vivax infection and low parasitic counts were significantly
      associated with relative diagnostic delay. One of the 14 uncomplicated P.
      falciparum patients and two of the 12 severe P. falciparum malaria patients who
      were followed up till day 28 had a late clinical failure. The others responded
      adequately to treatment both clinically and parasitologically. There was no
      treatment failure reported amongst any other species. This study, which is the
      first to assess the therapeutic response of imported malaria in Sri Lanka after
      elimination, demonstrates that the current antimalarial treatment policies and
      strategies in Sri Lanka have been effective against infections acquired overseas
      up until the end of year 2016.

PMID- 29182620
TI  - Broncho Vaxom (OM-85) modulates rhinovirus docking proteins on human airway
      epithelial cells via Erk1/2 mitogen activated protein kinase and cAMP.
AB  - BACKGROUND: Bronchial epithelial cells (BEC) are primary target for Rhinovirus
      infection through attaching to cell membrane proteins. OM-85, a bacterial
      extract, improves recovery of asthma and COPD patients after viral infections,
      but only part of the mechanism was addressed, by focusing on defined immune
      cells. OBJECTIVE: We therefore determined the effect of OM-85 on isolated primary
      human BEC of controls (n = 8), asthma patients (n = 10) and COPD patients (n =
      9). METHODS: BEC were treated with OM-85 alone (24 hours) or infected with
      Rhinovirus. BEC survival was monitored by manual cell counting and Rhinovirus
      replication by lytic activity. Immuno-blotting and ELISA were used to determine
      the expression of Rhinovirus interacting proteins: intracellular adhesion
      molecule (ICAM), major histocompatibility complex class II (MHC-2), complement
      component C1q receptor (C1q-R), inducible T-Cell co-stimulator (ICOS), its ligand
      ICOSL, and myeloid differentiation primary response gene 88 (Myd88); as well as
      for signal transducers Erk1/2, p38, JNK mitogen activated protein kinases MAPK),
      and cAMP. RESULTS: OM-85 significantly reduced Rhinovirus-induced BEC death and
      virus replication. OM-85 significantly increased the expression of virus
      interacting proteins C1q-R and beta-defensin in all 3 probes and groups, which
      was prevented by either Erk1/2 MAPK or cAMP inhibition. In addition, OM-85
      significantly reduced Rhinovirus induced expression of ICAM1 involving p38 MAPK.
      In BEC OM-85 had no significant effect on the expression of ICOS, ICOSL and MHC-2
      membrane proteins nor on the adaptor protein MyD88. CONCLUSION: The OM-85-induced
      increased of C1q-R and beta-defensin, both important for antigen presentation and
      phagocytosis, supports its activity in host cell's defence against Rhinovirus
      infection.

PMID- 29182621
TI  - Exploring the reproducibility of functional connectivity alterations in
      Parkinson's disease.
AB  - Since anatomic MRI is presently not able to directly discern neuronal loss in
      Parkinson's Disease (PD), studying the associated functional connectivity (FC)
      changes seems a promising approach toward developing non-invasive and non
      radioactive neuroimaging markers for this disease. While several groups have
      reported such FC changes in PD, there are also significant discrepancies between
      studies. Investigating the reproducibility of PD-related FC changes on
      independent datasets is therefore of crucial importance. We acquired resting
      state fMRI scans for 43 subjects (27 patients and 16 normal controls, with 2
      replicate scans per subject) and compared the observed FC changes with those
      obtained in two independent datasets, one made available by the PPMI consortium
      (91 patients, 18 controls) and a second one by the group of Tao Wu (20 patients,
      20 controls). Unfortunately, PD-related functional connectivity changes turned
      out to be non-reproducible across datasets. This could be due to disease
      heterogeneity, but also to technical differences. To distinguish between the two,
      we devised a method to directly check for disease heterogeneity using random
      splits of a single dataset. Since we still observe non-reproducibility in a large
      fraction of random splits of the same dataset, we conclude that functional
      heterogeneity may be a dominating factor behind the lack of reproducibility of FC
      alterations in different rs-fMRI studies of PD. While global PD-related
      functional connectivity changes were non-reproducible across datasets, we
      identified a few individual brain region pairs with marginally consistent FC
      changes across all three datasets. However, training classifiers on each one of
      the three datasets to discriminate PD scans from controls produced only low
      accuracies on the remaining two test datasets. Moreover, classifiers trained and
      tested on random splits of the same dataset (which are technically homogeneous)
      also had low test accuracies, directly substantiating disease heterogeneity.

PMID- 29182622
TI  - Cisplatin or LA-12 enhance killing effects of TRAIL in prostate cancer cells
      through Bid-dependent stimulation of mitochondrial apoptotic pathway but not
      caspase-10.
AB  - Searching for new strategies for effective elimination of human prostate cancer
      cells, we investigated the cooperative cytotoxic action of tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) and two platinum-based complexes,
      cisplatin or LA-12, and related molecular mechanisms. We demonstrated a notable
      ability of cisplatin or LA-12 to enhance the sensitivity of several human
      prostate cancer cell lines to TRAIL-induced cell death via an engagement of
      mitochondrial apoptotic pathway. This was accompanied by augmented Bid cleavage,
      Bak activation, loss of mitochondrial membrane potential, activation of caspase
      8, -10, -9, and -3, and XIAP cleavage. RNAi-mediated silencing of Bid or Bak in
      Bax-deficient DU 145 cells suppressed the drug combination-induced cytotoxicity,
      further underscoring the involvement of mitochondrial signaling. The caspase-10
      was dispensable for enhancement of cisplatin/LA-12 and TRAIL combination-induced
      cell death and stimulation of Bid cleavage. Importantly, we newly demonstrated LA
      12-mediated enhancement of TRAIL-induced cell death in cancer cells derived from
      human patient prostate tumor specimens. Our results provide convincing evidence
      that employing TRAIL combined with cisplatin/LA-12 could contribute to more
      effective killing of prostate cancer cells compared to the individual action of
      the drugs, and offer new mechanistic insights into their cooperative anticancer
      action.

PMID- 29182624
TI  - Maternal aging affects oocyte resilience to carbonyl cyanide-m
      chlorophenylhydrazone -induced mitochondrial dysfunction in cows.
AB  - Mitochondrial quality control is important for maintaining cellular and oocyte
      viability. In addition, aging affects mitochondrial quality in many cell types.
      In the present study, we examined how aging affects oocyte mitochondrial
      biogenesis and degeneration in response to induced mitochondrial dysfunction.
      Cumulus oocyte complexes were harvested from the ovaries of young (21-45 months)
      and aged (>=120 months) cows and treated for 2 hours with 10 MUM carbonyl cyanide
      m- chlorophenylhydrazone (CCCP), or a vehicle control, after which cumulus oocyte
      complexes were subjected to in vitro fertilization and culture. CCCP treatment
      reduced ATP content and increased reactive oxygen species (ROS) levels in the
      oocytes of both young and aged cows. When CCCP-treated cumulus oocyte complexes
      were subsequently cultured for 19 hours and/or subjected to fertilization, high
      ROS levels in oocytes and a low rate of blastocyst development was observed in
      oocytes derived from aged cows. In addition, we observed differential responses
      in mitochondrial biogenesis to CCCP treatment between young and aged cows. CCCP
      treatment enhanced mitochondrial biogenesis concomitant with upregulation of
      SIRT1 expression in oocytes of young, but not aged, cows. In conclusion, aging
      affects mitochondrial quality control and recuperation of oocytes following CCCP
      induced mitochondrial dysfunction.

PMID- 29182623
TI  - Immunotherapeutic efficacy of liposome-encapsulated refined allergen vaccines
      against Dermatophagoides pteronyssinus allergy.
AB  - Allergen specific immunotherapy (AIT) can modulate the allergic response causing
      a long-term symptom subsidence/abolishment which leads to reduced drug use and
      prevention of new sensitization. AIT of house dust mite allergy (HDM) using the
      mite crude extract (CE) as the therapeutic agent is not only less effective than
      the AIT for many other allergens, but also frequently causes adverse effects
      during the treatment course. In this study, mouse model of Dermatophagoides
      pteronyssinus (Dp) allergy was invented for testing therapeutic efficacies of
      intranasally administered liposome (L) encapsulated vaccines made of single Dp
      major allergens (L-Der p 1, L-Der p 2), combined allergens (L-Der p 1 and Der p
      2), and crude Dp extract (L-CE). The allergen sparing intranasal route was chosen
      as it is known that the effective cells induced at the nasal-associated lymphoid
      tissue can exert their activities at the lower respiratory tissue due to the
      common mucosal traffic. Liposome was chosen as the vaccine delivery vehicle and
      adjuvant as the micelles could reduce toxicity of the entrapped cargo. The Dp-CE
      allergic mice received eight doses of individual vaccines/placebo on alternate
      days. All vaccine formulations caused reduction of the Th2 response of the Dp
      allergic mice. However, only the vaccines made of single refined allergens
      induced expressions of immunosuppressive cytokines (TGF-beta, IL-35 and/or IL-10)
      which are the imperative signatures of successful AIT. The data emphasize the
      superior therapeutic efficacy of single refined major allergen vaccines than the
      crude allergenic extract vaccine.

PMID- 29182625
TI  - Regional brain morphometry in patients with traumatic brain injury based on acute
      and chronic-phase magnetic resonance imaging.
AB  - Traumatic brain injury (TBI) is caused by a sudden external force and can be very
      heterogeneous in its manifestation. In this work, we analyse T1-weighted magnetic
      resonance (MR) brain images that were prospectively acquired from patients who
      sustained mild to severe TBI. We investigate the potential of a recently proposed
      automatic segmentation method to support the outcome prediction of TBI.
      Specifically, we extract meaningful cross-sectional and longitudinal measurements
      from acute- and chronic-phase MR images. We calculate regional volume and
      asymmetry features at the acute/subacute stage of the injury (median: 19 days
      after injury), to predict the disability outcome of 67 patients at the chronic
      disease stage (median: 229 days after injury). Our results indicate that small
      structural volumes in the acute stage (e.g. of the hippocampus, accumbens,
      amygdala) can be strong predictors for unfavourable disease outcome. Further,
      group differences in atrophy are investigated. We find that patients with
      unfavourable outcome show increased atrophy. Among patients with severe
      disability outcome we observed a significantly higher mean reduction of cerebral
      white matter (3.1%) as compared to patients with low disability outcome (0.7%).

PMID- 29182626
TI  - Understanding the formation mechanism of lipid nanoparticles in microfluidic
      devices with chaotic micromixers.
AB  - Lipid nanoparticles (LNPs) or liposomes are the most widely used drug carriers
      for nanomedicines. The size of LNPs is one of the essential factors affecting
      drug delivery efficiency and therapeutic efficiency. Here, we demonstrated the
      effect of lipid concentration and mixing performance on the LNP size using
      microfluidic devices with the aim of understanding the LNP formation mechanism
      and controlling the LNP size precisely. We fabricated microfluidic devices with
      different depths, 11 MUm and 31 MUm, of their chaotic micromixer structures.
      According to the LNP formation behavior results, by using a low concentration of
      the lipid solution and the microfluidic device equipped with the 31 MUm chaotic
      mixer structures, we were able to produce the smallest-sized LNPs yet with a
      narrow particle size distribution. We also evaluated the mixing rate of the
      microfluidic devices using a laser scanning confocal microscopy and we estimated
      the critical ethanol concentration for controlling the LNP size. The critical
      ethanol concentration range was estimated to be 60-80% ethanol. Ten nanometer
      sized tuning of LNPs was achieved for the optimum residence time at the critical
      concentration using the microfluidic devices with chaotic mixer structures. The
      residence times at the critical concentration necessary to control the LNP size
      were 10, 15-25, and 50 ms time-scales for 30, 40, and 50 nm-sized LNPs,
      respectively. Finally, we proposed the LNP formation mechanism based on the
      determined LNP formation behavior and the critical ethanol concentration. The
      precise size-controlled LNPs produced by the microfluidic devices are expected to
      become carriers for next generation nanomedicines and they will lead to new and
      effective approaches for cancer treatment.

PMID- 29182627
TI  - Human papillomavirus DNA detection in plasma and cervical samples of women with a
      recent history of low grade or precancerous cervical dysplasia.
AB  - Circulating HPV DNA has been previously described in women with advanced stages
      of cervical cancer and has been suggested to be a prognostic marker of disease
      recurrences and metastases. Only a few studies have reported the presence of HPV
      DNA in bloodstream of patients with low grade or precancerous cervical lesions.
      This study aimed to define if HPV DNA could be detected in plasma samples of 120
      women referred for a recent history of cervical dysplasia who presented with
      lesions ranging from High Squamous Intraepithelial Lesion (H-SIL) to regressed
      normal cytology. HPV DNA detection was carried out in both plasma and cervical
      samples using type-specific real-time quantitative PCR assays identifying
      oncogenic HPV 16, 18, 31, 33, 45, 51 and 52. Overall, 34.2% (41/120) of plasma
      samples were shown to be positive for HPV DNA detection; HPV 45 (46.3%), HPV-51
      (29.6%), and HPV 16 (18.5%) were the most frequently identified genotypes. The
      rate of HPV detection in paired cervical and plasma samples increased with
      advancing disease stage, ranging from 15.4% in women with regressed lesions to
      38.9% in women with HSIL; HPV 16 resulted the most common genotype identified in
      women found to be HPV DNA positive in both cervical and plasma samples. Moreover,
      HPV 16 showed the highest median viral load value in both cervical and plasma
      samples, with 48,313 copies/104 cells and 1,099 copies/ml, respectively. Results
      obtained in this study confirm that HPV DNA can be detected and quantified in
      plasma samples of women with asymptomatic cervical infection. Further knowledge
      on HPV dissemination through the blood stream of women with cervical lesions
      would be very important in better understanding the natural history of HPV
      infection as well as its potential role in other distant tumors.

PMID- 29182628
TI  - Inhibitory activity of chokeberry, bilberry, raspberry and cranberry polyphenol
      rich extract towards adipogenesis and oxidative stress in differentiated 3T3-L1
      adipose cells.
AB  - Berries are a rich source of antioxidants and phytochemicals that have received
      considerable interest for their possible relations to human health. In this
      study, the anti-adipogenic effect of polyphenol-rich extract obtained from
      chokeberry Aronia melanocarpa (Michx.) Elliot, raspberry Rubus idaeus L.,
      bilberry Vaccinium myrtillus L. and cranberry Vaccinium macrocarpon Aiton fruits
      and its underlying molecular mechanisms were investigated in differentiated 3T3
      L1 adipose cells. Treatment with the extract (25-100 MUg/mL) significantly
      decreased lipid accumulation and reactive oxygen species generation in adipocytes
      without showing cytotoxicity. Real-time PCR analysis revealed that the extract at
      a concentration of 100 MUg/mL suppressed adipogenesis and lipogenesis via the
      down-regulation of PPARgamma (67%), C/EBPalpha (72%), SREBP1 (62%), aP2 (24%),
      FAS (32%), LPL (40%), HSL (39%), and PLIN1 (32%) gene expression. Moreover, the
      extract significantly increased the expression of adiponectin (4.4-fold) and
      decreased leptin expression (90%) and respectively regulated the production of
      these adipokines in 3T3-L1 adipocytes. The obtained results suggest that the
      analyzed extract may be a promising source of bioactive compounds that support
      long-term weight maintenance and promote the effective management of obesity.

PMID- 29182629
TI  - Effects of peroxisome proliferator activated receptors (PPAR)-gamma and -alpha
      agonists on cochlear protection from oxidative stress.
AB  - Various insults cause ototoxicity in mammals by increasing oxidative stress
      leading to apoptosis of auditory hair cells (HCs). The thiazolidinediones (TZDs;
      e.g., pioglitazone) and fibrate (e.g., fenofibrate) drugs are used for the
      treatment of diabetes and dyslipidemia. These agents target the peroxisome
      proliferator-activated receptors, PPARgamma and PPARalpha, which are
      transcription factors that influence glucose and lipid metabolism, inflammation,
      and organ protection. In this study, we explored the effects of pioglitazone and
      other PPAR agonists to prevent gentamicin-induced oxidative stress and apoptosis
      in mouse organ of Corti (OC) explants. Western blots showed high levels of
      PPARgamma and PPARalpha proteins in mouse OC lysates. Immunofluorescence assays
      indicated that PPARgamma and PPARalpha proteins are present in auditory HCs and
      other cell types in the mouse cochlea. Gentamicin treatment induced production of
      reactive oxygen species (ROS), lipid peroxidation, caspase activation, PARP-1
      cleavage, and HC apoptosis in cultured OCs. Pioglitazone mediated its anti
      apoptotic effects by opposing the increase in ROS induced by gentamicin, which
      inhibited the subsequent formation of 4-hydroxy-2-nonenal (4-HNE) and activation
      of pro-apoptotic mediators. Pioglitazone mediated its effects by upregulating
      genes that control ROS production and detoxification pathways leading to
      restoration of the reduced:oxidized glutathione ratio. Structurally diverse PPAR
      agonists were protective of HCs. Pioglitazone (PPARgamma-specific), tesaglitazar
      (PPARgamma/alpha-specific), and fenofibric acid (PPARalpha-specific) all provided
      >90% protection from gentamicin toxicity by regulation of overlapping subsets of
      genes controlling ROS detoxification. This study revealed that PPARs play
      important roles in the cochlea, and that PPAR-targeting drugs possess therapeutic
      potential as treatment for hearing loss.

PMID- 29182630
TI  - Connectivity and systemic resilience of the Great Barrier Reef.
AB  - Australia's iconic Great Barrier Reef (GBR) continues to suffer from repeated
      impacts of cyclones, coral bleaching, and outbreaks of the coral-eating crown-of
      thorns starfish (COTS), losing much of its coral cover in the process. This
      raises the question of the ecosystem's systemic resilience and its ability to
      rebound after large-scale population loss. Here, we reveal that around 100 reefs
      of the GBR, or around 3%, have the ideal properties to facilitate recovery of
      disturbed areas, thereby imparting a level of systemic resilience and aiding its
      continued recovery. These reefs (1) are highly connected by ocean currents to the
      wider reef network, (2) have a relatively low risk of exposure to disturbances so
      that they are likely to provide replenishment when other reefs are depleted, and
      (3) have an ability to promote recovery of desirable species but are unlikely to
      either experience or spread COTS outbreaks. The great replenishment potential of
      these 'robust source reefs', which may supply 47% of the ecosystem in a single
      dispersal event, emerges from the interaction between oceanographic conditions
      and geographic location, a process that is likely to be repeated in other reef
      systems. Such natural resilience of reef systems will become increasingly
      important as the frequency of disturbances accelerates under climate change.

PMID- 29182631
TI  - The expanding epidemic of HIV-1 in the Russian Federation.
AB  - In a Perspective, Chris Beyrer and coauthors discuss the threat of HIV to health
      in the Russian Federation.

PMID- 29182632
TI  - A comparison of the effects of fire on rodent abundance and diversity in the
      Great Basin and Mojave Deserts.
AB  - As invasive grasses and fire increase in frequency and extent in North American
      deserts, they have the potential to affect animal communities through bottom-up
      forces. We experimentally tested the effects of fire on rodent communities of the
      Great Basin and Mojave Deserts. Fire decreased the abundance, richness, and
      diversity of rodents in the Great Basin after fire. In the Mojave, abundance was
      unaffected and diversity and species richness were greater on burned than
      unburned plots 4 months after fire. The effects of fire on rodent communities
      tended to decrease over time. The differences in effects between the deserts may
      be due to differences in the foraging preferences of the dominant species at each
      site. As these species are primarily herbivorous, short-term changes to the
      rodent community could have long-term implications by affecting the recovery of
      the plant community after fire.

PMID- 29182633
TI  - Extensive virologic and immunologic characterization in an HIV-infected
      individual following allogeneic stem cell transplant and analytic cessation of
      antiretroviral therapy: A case study.
AB  - BACKGROUND: Notwithstanding 1 documented case of HIV-1 cure following allogeneic
      stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV
      1 positive individuals have failed to cure HIV-1 infection. The aim of our study
      was to describe changes in the HIV reservoir in a single chronically HIV-infected
      patient on suppressive antiretroviral therapy who underwent allo-SCT for
      treatment of acute lymphoblastic leukemia. METHODS AND FINDINGS: We prospectively
      collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55
      year-old man with chronic HIV infection before and after allo-SCT to measure the
      size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic
      changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable
      by multiple measures-including PCR measurements of both total and integrated HIV
      1 DNA, replication-competent virus measurement by large cell input quantitative
      viral outgrowth assay, and in situ hybridization of colon tissue-the patient
      consented to an analytic treatment interruption (ATI) with frequent clinical
      monitoring. He remained aviremic off antiretroviral therapy until ATI day 288,
      when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to
      1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding
      plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA
      detected in circulating PBMCs before transplantation. The main limitations of
      this study are the insensitivity of reservoir measurements, and the fact that it
      describes a single case. CONCLUSIONS: allo-SCT led to a significant reduction in
      the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1
      replication. Phylogenetic analyses suggest that the origin of rebound virus was
      distinct from the viruses identified pre-transplant in the PBMCs.

PMID- 29182634
TI  - Direct provision versus facility collection of HIV self-tests among female sex
      workers in Uganda: A cluster-randomized controlled health systems trial.
AB  - BACKGROUND: HIV self-testing allows HIV testing at any place and time and without
      health workers. HIV self-testing may thus be particularly useful for female sex
      workers (FSWs), who should test frequently but face stigma and financial and time
      barriers when accessing healthcare facilities. METHODS AND FINDINGS: We conducted
      a cluster-randomized controlled health systems trial among FSWs in Kampala,
      Uganda, to measure the effect of 2 HIV self-testing delivery models on HIV
      testing and linkage to care outcomes. FSW peer educator groups (1 peer educator
      and 8 participants) were randomized to either (1) direct provision of HIV self
      tests, (2) provision of coupons for free collection of HIV self-tests in a
      healthcare facility, or (3) standard of care HIV testing. We randomized 960
      participants in 120 peer educator groups from October 18, 2016, to November 16,
      2016. Participants' median age was 28 years (IQR 24-32). Our prespecified primary
      outcomes were self-report of any HIV testing at 1 month and at 4 months; our
      prespecified secondary outcomes were self-report of HIV self-test use, seeking
      HIV-related medical care and ART initiation. In addition, we analyzed 2 secondary
      outcomes that were not prespecified: self-report of repeat HIV testing-to
      understand the intervention effects on frequent testing-and self-reported
      facility-based testing-to quantify substitution effects. Participants in the
      direct provision arm were significantly more likely to have tested for HIV than
      those in the standard of care arm, both at 1 month (risk ratio [RR] 1.33, 95% CI
      1.17-1.51, p < 0.001) and at 4 months (RR 1.14, 95% CI 1.07-1.22, p < 0.001).
      Participants in the direct provision arm were also significantly more likely to
      have tested for HIV than those in the facility collection arm, both at 1 month
      (RR 1.18, 95% CI 1.07-1.31, p = 0.001) and at 4 months (RR 1.03, 95% CI 1.01
      1.05, p = 0.02). At 1 month, fewer participants in the intervention arms had
      sought medical care for HIV than in the standard of care arm, but these
      differences were not significant and were reduced in magnitude at 4 months. There
      were no statistically significant differences in ART initiation across study
      arms. At 4 months, participants in the direct provision arm were significantly
      more likely to have tested twice for HIV than those in the standard of care arm
      (RR 1.51, 95% CI 1.29-1.77, p < 0.001) and those in the facility collection arm
      (RR 1.22, 95% CI 1.08-1.37, p = 0.001). Participants in the HIV self-testing arms
      almost completely replaced facility-based testing with self-testing. Two adverse
      events related to HIV self-testing were reported: interpersonal violence and
      mental distress. Study limitations included self-reported outcomes and limited
      generalizability beyond FSWs in similar settings. CONCLUSIONS: In this study, HIV
      self-testing appeared to be safe and increased recent and repeat HIV testing
      among FSWs. We found that direct provision of HIV self-tests was significantly
      more effective in increasing HIV testing among FSWs than passively offering HIV
      self-tests for collection in healthcare facilities. HIV self-testing could play
      an important role in supporting HIV interventions that require frequent HIV
      testing, such as HIV treatment as prevention, behavior change for transmission
      reduction, and pre-exposure prophylaxis. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02846402.

PMID- 29182635
TI  - The evolution and adaptation of A-to-I RNA editing.
AB  - Adenosine-to-inosine (A-to-I) RNA editing is an important post-transcriptional
      modification that affects the information encoded from DNA to RNA to protein. RNA
      editing can generate a multitude of transcript isoforms and can potentially be
      used to optimize protein function in response to varying conditions. In light of
      this and the fact that millions of editing sites have been identified in many
      different species, it is interesting to examine the extent to which these sites
      have evolved to be functionally important. In this review, we discuss results
      pertaining to the evolution of RNA editing, specifically in humans, cephalopods,
      and Drosophila. We focus on how comparative genomics approaches have aided in the
      identification of sites that are likely to be advantageous. The use of RNA
      editing as a mechanism to adapt to varying environmental conditions will also be
      reviewed.

PMID- 29182636
TI  - Identification of differences in health impact modelling of salt reduction.
AB  - We examined whether specific input data and assumptions explain outcome
      differences in otherwise comparable health impact assessment models. Seven
      population health models estimating the impact of salt reduction on morbidity and
      mortality in western populations were compared on four sets of key features,
      their underlying assumptions and input data. Next, assumptions and input data
      were varied one by one in a default approach (the DYNAMO-HIA model) to examine
      how it influences the estimated health impact. Major differences in outcome were
      related to the size and shape of the dose-response relation between salt and
      blood pressure and blood pressure and disease. Modifying the effect sizes in the
      salt to health association resulted in the largest change in health impact
      estimates (33% lower), whereas other changes had less influence. Differences in
      health impact assessment model structure and input data may affect the health
      impact estimate. Therefore, clearly defined assumptions and transparent reporting
      for different models is crucial. However, the estimated impact of salt reduction
      was substantial in all of the models used, emphasizing the need for public health
      actions.

PMID- 29182637
TI  - Local ecological knowledge and its relationship with biodiversity conservation
      among two Quilombola groups living in the Atlantic Rainforest, Brazil.
AB  - Information on the knowledge, uses, and abundance of natural resources in local
      communities can provide insight on conservation status and conservation
      strategies in these locations. The aim of this research was to evaluate the uses,
      knowledge and conservation status of plants in two Quilombolas (descendants of
      slaves of African origin) communities in the Atlantic rainforest of Brazil, Sao
      Sebastiao da Boa Vista (SSBV) and Sao Bento (SB). We used a combination of
      ethnobotanical and ecological survey methods to ask: 1) What ethnobotanical
      knowledge do the communities hold? 2) What native species are most valuable to
      them? 3) What is the conservation status of the native species used? Thirteen
      local experts described the names and uses of 212 species in SSBV (105 native
      species) and 221 in SB (96 native species). Shannon Wiener diversity and Pielou's
      Equitability indices of ethnobotanical knowledge of species were very high
      (5.27/0.96 and 5.28/0.96, respectively). Species with the highest cultural
      significance and use-value indexes in SSBV were Dalbergia hortensis (26/2.14),
      Eremanthus erythropappus (6.88/1), and Tibouchina granulosa (6.02/1); while
      Piptadenia gonoacantha (3.32/1), Sparattosperma leucanthum (3.32/1) and Cecropia
      glaziovii (3.32/0.67) were the highest in SB. Thirty-three native species ranked
      in the highest conservation priority category at SSBV and 31 at SB. D. hortensis
      was noteworthy because of its extremely high cultural importance at SSBV, and its
      categorization as a conservation priority in both communities. This information
      can be used towards generating sustainable use and conservation plans that are
      appropriate for the local communities.

PMID- 29182638
TI  - Respondent-driven sampling for identification of HIV- and HCV-infected people who
      inject drugs and men who have sex with men in India: A cross-sectional, community
      based analysis.
AB  - BACKGROUND: A major barrier to achieving ambitious targets for global control of
      HIV and hepatitis C virus (HCV) is low levels of awareness of infection among key
      populations such as men who have sex with men (MSM) and people who inject drugs
      (PWID). We explored the potential of a strategy routinely used for surveillance
      in these groups, respondent-driven sampling (RDS), to be used as an intervention
      to identify HIV- and HCV-infected PWID and MSM who are unaware of their status
      and those who are viremic across 26 Indian cities at various epidemic stages.
      METHODS AND FINDINGS: Data were collected as part of the baseline assessment of
      an ongoing cluster-randomized trial. RDS was used to accrue participants at 27
      sites (15 PWID sites and 12 MSM sites) selected to reflect varying stages of the
      HIV epidemic among MSM and PWID in India. A total of 56 seeds recruited a sample
      of 26,447 persons (approximately 1,000 participants per site) between October 1,
      2012, and December 19, 2013. Across MSM sites (n = 11,997), the median age was 25
      years and the median number of lifetime male partners was 8. Across PWID sites (n
      = 14,450), 92.4% were male, the median age was 30 years, and 87.5% reported
      injection in the prior 6 months. RDS identified 4,051 HIV-infected persons, of
      whom 2,325 (57.4%) were unaware of their HIV infection and 2,816 (69.5%) were HIV
      viremic. It also identified 5,777 HCV-infected persons, of whom 5,337 (92.4%)
      were unaware that they were infected with HCV and 4,728 (81.8%) were viremic. In
      the overall sample (both MSM and PWID), the prevalence of HIV-infected persons
      who were unaware of their status increased with sampling depth, from 7.9% in
      participants recruited in waves 1 through 5 to 12.8% among those recruited in
      waves 26 and above (p-value for trend < 0.001). The overall detection rate of
      people unaware of their HIV infection was 0.5 persons per day, and the detection
      rate of HIV-infected persons with viremia (regardless of their awareness status)
      was 0.7 per day. The detection rate of HIV viremic individuals was positively
      associated with underlying HIV prevalence and the prevalence of HIV viremia
      (linear regression coefficient per 1-percentage-point increase in prevalence:
      0.05 and 0.07, respectively). The median detection rate of PWID who were unaware
      of their HCV infection was 2.5 per day. The cost of identifying 1 unaware HIV
      infected individual ranged from US$51 to US$2,072 across PWID sites and from
      US$189 to US$5,367 across MSM sites. The mean additional cost of identifying 1
      unaware HCV-infected PWID was US$13 (site range: US$7-US$140). Limitations of the
      study include the exclusivity of study sites to India, lack of prior HIV/HCV
      diagnosis confirmation with clinic records, and lack of cost data from other case
      finding approaches commonly used in India. CONCLUSIONS: In this study, RDS was
      able to rapidly identify at nominal cost a substantial number of unaware and
      viremic HIV-infected and HCV-infected individuals who were currently not being
      reached by existing programs and who were at high risk for transmission.
      Combining RDS (or other network-driven recruitment approaches) with strategies
      focused on linkage to care, particularly in high-burden settings, may be a viable
      option for achieving the 90-90-90 targets in key populations in resource-limited
      settings.

PMID- 29182639
TI  - Mycophenolate mofetil prevents the delayed T cell response after pilocarpine
      induced status epilepticus in mice.
AB  - Growing clinical and laboratory evidence corroborates a role for the immune
      system in the pathophysiology of epilepsy. In order to delineate the immune
      response following pilocarpine-induced status epilepticus (SE) in the mouse, we
      monitored the kinetics of leukocyte presence in the hippocampus over the period
      of four weeks. SE was induced following a ramping protocol of pilocarpine
      injection into 4-5 weeks old C57BL/6 mice. Brains were removed at days 1-4, 14 or
      28 after SE, and the hippocampi were analyzed via flow cytometry, via
      quantitative reverse transcriptase PCR (qRT-PCR) and via immunohistochemistry.
      Epileptogenesis was confirmed by Timm staining of mossy fiber sprouting in the
      inner molecular layer of the dentate gyrus. The flow cytometry data revealed a
      biphasic immune response following pilocarpine-induced SE with a transient
      increase in activated CD11b+ and F4/80+ macrophages within the first four days
      replaced by an increase in CD3+ T-lymphocytes around day 28. This delayed T cell
      response was confirmed via qRT-PCR and via immunohistochemistry. In addition, qRT
      PCR data could show that the delayed T cell response was associated with an
      increased CD8/CD4 ratio indicating a cytotoxic T cell response after SE.
      Intriguingly, early intervention with mycophenolate mofetil administration on
      days 0-3 after SE prevented this delayed T cell response. These results show an
      orchestrated immunological sequela and provide evidence that the delayed T cell
      response is sensitive to early immunomodulatory intervention.

PMID- 29182640
TI  - Changes in the interstitial cells of Cajal and neuronal nitric oxide synthase
      positive neuronal cells with aging in the esophagus of F344 rats.
AB  - The aging-associated cellular and molecular changes in esophagus have not been
      established, yet. Thus we evaluated histological structure, interstitial cells of
      Cajal (ICCs), neuronal nitric oxide synthase (nNOS)-positive cells, and
      contractility in the esophagus of Fischer 344 rat at different ages (6-, 31-, 74
      weeks, and 2-years). The lamina propria thickness and endomysial area were
      calculated. The immunoreactivity of c-Kit, nNOS and protein gene product (PGP)
      9.5 was counted after immunohistochemistry. Expression of c-Kit, stem cell factor
      (SCF), nNOS and PGP 9.5 mRNA was measured by real-time PCR, and expression of c
      Kit and nNOS protein was detected by Western blot. Isovolumetric contractile
      force measurement and electrical field stimulation (EFS) were conducted. The
      lamina propria thickness increased (6 week vs 2 year, P = 0.005) and the
      endomysial area of longitudinal muscle decreased with aging (6 week vs 2 year,
      P<0.001), while endomysial area of circular muscle did not significantly
      decrease. The proportions of NOS-immunoreactive cells and c-Kit-immunoreactive
      areas declined with aging (6 week vs 2 year; P<0.001 and P = 0.004,
      respectively), but there was no significant change of PGP 9.5-immunopositiviy.
      The expressions of nNOS, c-Kit and SCF mRNA also reduced with aging (6 week vs 2
      year; P = 0.006, P = 0.001 and P = 0.006, respectively), while the change of PGP
      9.5 mRNA expression was not significant. Western blot showed the significant
      decreases of nNOS and c-Kit protein expression with aging (6 week vs 2 year; P =
      0.008 and P = 0.012, respectively). The EFS-induced esophageal contractions
      significantly decreased in 2-yr-old rat compared with 6-wk-old rats, however, L
      NG-Nitroarginine methylester did not significantly increase the spontaneous and
      EFS-induced contractions in the 6-wk- and 2-yr-old rat esophagus. In conclusion,
      an increase of lamina propria thickness, a decrease of endomysial area, c-Kit,
      SCF and NOS expression with preserved total enteric neurons, and contractility in
      aged rat esophagus may explain the aging-associated esophageal dysmotility.

PMID- 29182641
TI  - Treatment eligibility and retention in clinical HIV care: A regression
      discontinuity study in South Africa.
AB  - BACKGROUND: Loss to follow-up is high among HIV patients not yet receiving
      antiretroviral therapy (ART). Clinical trials have demonstrated the clinical
      efficacy of early ART; however, these trials may miss an important real-world
      consequence of providing ART at diagnosis: its impact on retention in care.
      METHODS AND FINDINGS: We examined the effect of immediate (versus deferred) ART
      on retention in care using a regression discontinuity design. The analysis
      included all patients (N = 11,306) entering clinical HIV care with a first CD4
      count between 12 August 2011 and 31 December 2012 in a public-sector HIV care and
      treatment program in rural South Africa. Patients were assigned to immediate
      versus deferred ART eligibility, as determined by a CD4 count < 350 cells/MUl,
      per South African national guidelines. Patients referred to pre-ART care were
      instructed to return every 6 months for CD4 monitoring. Patients initiated on ART
      were instructed to return at 6 and 12 months post-initiation and annually
      thereafter for CD4 and viral load monitoring. We assessed retention in HIV care
      at 12 months, as measured by the presence of a clinic visit, lab test, or ART
      initiation 6 to 18 months after initial CD4 test. Differences in retention
      between patients presenting with CD4 counts just above versus just below the 350
      cells/MUl threshold were estimated using local linear regression models with a
      data-driven bandwidth and with the algorithm for selecting the bandwidth chosen
      ex ante. Among patients with CD4 counts close to the 350-cells/MUl threshold,
      having an ART-eligible CD4 count (<350 cells/MUl) was associated with higher 12
      month retention than not having an ART-eligible CD4 count (50% versus 32%), an
      intention-to-treat risk difference of 18 percentage points (95% CI 11 to 23; p <
      0.001). The decision to start ART was determined by CD4 count for one in four
      patients (25%) presenting close to the eligibility threshold (95% CI 20% to 31%;
      p < 0.001). In this subpopulation, having an ART-eligible CD4 count was
      associated with higher 12-month retention than not having an ART-eligible CD4
      count (91% versus 21%), a complier causal risk difference of 70 percentage points
      (95% CI 42 to 98; p < 0.001). The major limitations of the study are the
      potential for limited generalizability, the potential for outcome
      misclassification, and the absence of data on longer-term health outcomes.
      CONCLUSIONS: Patients who were eligible for immediate ART had dramatically higher
      retention in HIV care than patients who just missed the CD4-count eligibility
      cutoff. The clinical and population health benefits of offering immediate ART
      regardless of CD4 count may be larger than suggested by clinical trials.

PMID- 29182642
TI  - Elevated N-telopeptide as a potential diagnostic marker for bone metastasis in
      lung cancer: A meta-analysis.
AB  - BACKGROUND: Growing evidence indicates that the cross-linked N-telopeptide of
      type I collagen (NTx) is likely to be involved in the development of bone
      metastasis among lung cancer patients. We perform a meta-analysis to disclose the
      correlation between bone metastasis and NTx and also to evaluate its value in
      diagnosis of bone metastasis (BM) in lung cancer. METHOD: Electronic databases
      were searched and calculated the weighted mean difference (WMD) with 95%
      confidence interval (CI) to assess the expression difference of NTx between BM+
      and BM- lung cancer patients. Moreover, we conducted a sensitivity and
      specificity test and drew a summary receiver operating characteristic curve
      (SROC) to assess the diagnostic value of NTx in discerning bone metastasis.
      RESULTS: A total of eleven studies with 1108 individuals were included in this
      analysis. The results showed an increased NTx was correlated with the incidence
      of lung cancer (P < 0.001). The overall sensitivity and specificity of serum NTx
      (sNTx) for discerning bone metastasis was 0.74 (95% CI = 0.67 to 0.79) and 0.85
      (95% CI = 0.80 to 0.89), respectively. As for urine NTx (uNTx) the pooled
      sensitivity and specificity was 0.77(95% CI = 0.67 to 0.86) and 0.81(95% CI =
      0.76 to 0.86). The area under the SROC curve was 0.8889(SE = 0.0255) and
      0.8655(SE = 0.0254) for sNTx and uNTx respectively. CONCLUSIONS: The elevation of
      NTx in lung cancer was positively related with the development and progression of
      bone metastasis. A higher specificity over sensitivity of NTx suggested that it
      is a more accurate biomarker to distinguish patients without bone metastasis.
      Regarding SROC curve, sNTx may be a better choice.

PMID- 29182643
TI  - How do adults and teens with self-declared Autism Spectrum Disorder experience
      eye contact? A qualitative analysis of first-hand accounts.
AB  - A tendency to avoid eye contact is an early indicator of Autism Spectrum Disorder
      (ASD), and difficulties with eye contact often persist throughout the lifespan.
      Eye contact difficulties may underlie social cognitive deficits in ASD, and can
      create significant social and occupational barriers. Thus, this topic has
      received substantial research and clinical attention. In this study, we used
      qualitative methods to analyze self-reported experiences with eye contact as
      described by teens and adults with self-declared ASD. Results suggest people with
      a self- declared ASD diagnosis experience adverse emotional and physiological
      reactions, feelings of being invaded, and sensory overload while making eye
      contact, in addition to difficulties understanding social nuances, and
      difficulties receiving and sending nonverbal information. Some data support
      existing mindblindness frameworks, and hyperarousal or hypoarousal theories of
      eye contact, but we also present novel findings unaccounted for by existing
      frameworks. Additionally, we highlight innovative strategies people with self
      declared ASD have devised to overcome or cope with their eye contact
      difficulties.

PMID- 29182644
TI  - Temporal trends in adolescents' self-reported psychosomatic health complaints
      from 1980-2016: A systematic review and meta-analysis.
AB  - OBJECTIVE: There is increasing concern that mental health may be deteriorating in
      recent generations of adolescents. It is unclear whether this is the case for
      self-reported psychosomatic health complaints (PSHC). METHOD: We conducted a
      systematic review and meta-analysis of published primary studies on PSHC in the
      general adolescent population over time. The primary databases were MEDLINE,
      Embase and PsycINFO, which were searched from inception to November 2016. Studies
      were included if they involved an observational design, presented self-reported
      data from participants aged 10-19 years and included data from at least two time
      points, five years apart. Inclusion and study quality were assessed by two
      independent reviewers. RESULTS: Twenty-one studies were included; 18 reported
      trends on the prevalence of PSHC in a single country, while three studies
      reported on multiple countries. In total, over seven million adolescents from 36
      countries in Europe, North America, Israel and New Zealand were represented,
      covering the period 1982-2013. In the descriptive analysis, 10 studies indicated
      a trend of increasing PSHC, eight showed a stable trend and three showed a
      decreasing trend at certain points in time. The results from the meta-analysis
      showed a mean odds ratio (OR) of 1.04 (K = 139, 95% CI 1.01-1.08) for PSHC from
      1982 to 2013, thus indicating a minor increase in general. In the subgroup
      analysis, this minor increase was observed mainly between the 1980s and 2000s,
      while the trend appeared to be more stable between the 2000s and 2010s. Some
      differences were also found between multinational subregions. Findings from
      subgroup analysis, however, only supported a significant increasing trend in
      Northern Europe. CONCLUSION: There may have been a minor increasing trend in
      adolescent self-rated PSHC between the 1980 and 2000s, but has become more stable
      since the 2010s, from a multinational perspective. Northern Europe was the only
      region to show a clearly significant minor increasing trend, without being the
      region with the highest total prevalence of PSHC at the present time. The
      discrepant trends regarding PSHC between regions and the reliance on self
      reported data may reflect true changes in the occurrence of PSHC in the
      adolescent population. However, they may also reflect changes in how adolescents
      perceive and report health complaints. OTHER: PROSPERO registration 2016:
      CRD42016048300.

PMID- 29182645
TI  - HLA and non-HLA genes and familial predisposition to autoimmune diseases in
      families with a child affected by type 1 diabetes.
AB  - Genetic predisposition could be assumed to be causing clustering of autoimmunity
      in individuals and families. We tested whether HLA and non-HLA loci associate
      with such clustering of autoimmunity. We included 1,745 children with type 1
      diabetes from the Finnish Pediatric Diabetes Register. Data on personal or family
      history of autoimmune diseases were collected with a structured questionnaire
      and, for a subset, with a detailed search for celiac disease and autoimmune
      thyroid disease. Children with multiple autoimmune diseases or with multiple
      affected first- or second-degree relatives were identified. We analysed type 1
      diabetes related HLA class II haplotypes and genotyped 41 single nucleotide
      polymorphisms (SNPs) outside the HLA region. The HLA-DR4-DQ8 haplotype was
      associated with having type 1 diabetes only whereas the HLA-DR3-DQ2 haplotype was
      more common in children with multiple autoimmune diseases. Children with multiple
      autoimmune diseases showed nominal association with RGS1 (rs2816316), and
      children coming from an autoimmune family with rs11711054 (CCR3-CCR5). In
      multivariate analyses, the overall effect of non-HLA SNPs on both phenotypes was
      evident, associations with RGS1 and CCR3-CCR5 region were confirmed and
      additional associations were implicated: NRP1, FUT2, and CD69 for children with
      multiple autoimmune diseases. In conclusion, HLA-DR3-DQ2 haplotype and some non
      HLA SNPs contribute to the clustering of autoimmune diseases in children with
      type 1 diabetes and in their families.

PMID- 29182647
TI  - Influence of different feeding regimes on the survival, growth, and biochemical
      composition of Acropora coral recruits.
AB  - Heterotrophic feeding in newly-settled coral planulae can potentially improve
      survivorship and accelerate early development in some species; however, an
      optimal diet to facilitate this does not currently exist. This study evaluated
      the efficacy of three heterotrophic feeding regimes (enriched rotifers,
      unfiltered seawater, and a novel, particulate diet), against a wholly
      phototrophic treatment on Acropora hyacinthus, A. loripes, A. millepora, and A.
      tenuis recruits, over 93 days post-settlement. The unfiltered seawater treatment
      recorded maximum survival for all species (A. hyacinthus 95.9+/-8.0%, A. loripes:
      74.3+/-11.5%, A. millepora: 67+/-12.7%, A. tenuis: 53.2+/-11.3%), although not
      significant. Growth (% surface area gain) was also greatest in the unfiltered
      seawater, and this was significant for A. millepora (870+/-307%) and A. tenuis
      (693+/-91.8%) (p<0.05). Although total lipid concentration was relatively stable
      across treatments, the lipid class composition exhibited species-specific
      responses to each treatment. Lower saturated and higher polyunsaturated fatty
      acids appeared beneficial to recruit performance, particularly in the unfiltered
      seawater, which generally contained the highest levels of 20:5n-3 (EPA), 22:6n-3
      (DHA), and 20:4n-6 (ARA). The present study demonstrates the capacity of a
      nutritionally adequate and readily accepted heterotrophic feeding regime to
      increase coral recruit survival, growth, and health, which can greatly reduce the
      time required in cost- and labour-intensive culture.

PMID- 29182646
TI  - Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle
      identifies the periodically expressed mRNAs and their multiple levels of control.
AB  - Trypanosoma cruzi is the protozoan parasite causing American trypanosomiasis or
      Chagas disease, a neglected parasitosis with important human health impact in
      Latin America. The efficacy of current therapy is limited, and its toxicity is
      high. Since parasite proliferation is a fundamental target for rational drug
      design, we sought to progress into its understanding by applying a genome-wide
      approach. Treating a TcI linage strain with hydroxyurea, we isolated
      epimastigotes in late G1, S and G2/M cell cycle stages at 70% purity. The
      sequencing of each phase identified 305 stage-specific transcripts (1.5-fold
      change, p<=0.01), coding for conserved cell cycle regulated proteins and numerous
      proteins whose cell cycle dependence has not been recognized before. Comparisons
      with the parasite T. brucei and the human host reveal important differences. The
      meta-analysis of T. cruzi transcriptomic and ribonomic data indicates that cell
      cycle regulated mRNAs are subject to sub-cellular compartmentalization.
      Compositional and structural biases of these genes- including CAI, GC content,
      UTR length, and polycistron position- may contribute to their regulation. To
      discover nucleotide motifs responsible for the co-regulation of cell cycle
      regulated genes, we looked for overrepresented motifs at their UTRs and found a
      variant of the cell cycle sequence motif at the 3' UTR of most of the S and G2
      stage genes. We additionally identified hairpin structures at the 5' UTRs of a
      high proportion of the transcripts, suggesting that periodic gene expression
      might also rely on translation initiation in T. cruzi. In summary, we report a
      comprehensive list of T. cruzi cell cycle regulated genes, including many
      previously unstudied proteins, we show evidence favoring a multi-step control of
      their expression, and we identify mRNA motifs that may mediate their regulation.
      Our results provide novel information of the T. cruzi proliferative proteins and
      the integrated levels of their gene expression control.

PMID- 29182648
TI  - The neural response properties and cortical organization of a rapidly adapting
      muscle sensory group response that overlaps with the frequencies that elicit the
      kinesthetic illusion.
AB  - Kinesthesia is the sense of limb movement. It is fundamental to efficient motor
      control, yet its neurophysiological components remain poorly understood. The
      contributions of primary muscle spindles and cutaneous afferents to the
      kinesthetic sense have been well studied; however, potential contributions from
      muscle sensory group responses that are different than the muscle spindles have
      not been ruled out. Electrophysiological recordings in peripheral nerves and
      brains of male Sprague Dawley rats with a degloved forelimb preparation provide
      evidence of a rapidly adapting muscle sensory group response that overlaps with
      vibratory inputs known to generate illusionary perceptions of limb movement in
      humans (kinesthetic illusion). This group was characteristically distinct from
      type Ia muscle spindle fibers, the receptor historically attributed to limb
      movement sensation, suggesting that type Ia muscle spindle fibers may not be the
      sole carrier of kinesthetic information. The sensory-neural structure of muscles
      is complex and there are a number of possible sources for this response group;
      with Golgi tendon organs being the most likely candidate. The rapidly adapting
      muscle sensory group response projected to proprioceptive brain regions, the
      rodent homolog of cortical area 3a and the second somatosensory area (S2), with
      similar adaption and frequency response profiles between the brain and peripheral
      nerves. Their representational organization was muscle-specific (myocentric) and
      magnified for proximal and multi-articulate limb joints. Projection to
      proprioceptive brain areas, myocentric representational magnification of muscles
      prone to movement error, overlap with illusionary vibrational input, and resonant
      frequencies of volitional motor unit contraction suggest that this group response
      may be involved with limb movement processing.

PMID- 29182650
TI  - Predictors of adherence to a new erythropoiesis-stimulating agent inpatient
      ordering policy: A cross-sectional study.
AB  - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are recommended for treating
      anemia in patients with chronic kidney disease and end-stage renal disease.
      However, misappropriate and over-use of these agents can be costly and
      unnecessary in some settings. OBJECTIVE: The primary aim was to identify
      predictors of adherence to a newly approved ESA inpatient ordering policy. The
      secondary aims were to evaluate the impact of a 5-day delay in the initiation of
      ESA therapy on ESA usage, hemoglobin (Hb) levels, and costs. METHODS: This
      retrospective observational record review included a sample of adult patients
      admitted to four tertiary care hospitals from November 1, 2013 to August 31,
      2014. Multivariable logistic and linear regression analyses were used to
      calculate the odds of adherence to the new ESA inpatient ordering policy and the
      impact of this policy on discharge Hb level, respectively. RESULTS: A total of
      242 patients were included. The majority of the prescribers (77%) adhered to the
      new ESA ordering policy. Hemoglobin (OR = 1.306; 95% CI: 1.03-1.65) and ferritin
      (OR = 3.91; 95% CI: 1.23-12.51) levels at admission and length of hospital stay
      were positively correlated with the odds of patients receiving ESAs after day 5
      (OR = 1.12; 95% CI:1.05-1.20). Furthermore, adherence to the new policy did not
      have a significant impact on discharge Hb level (beta = 0.02349; P = 0.895).
      CONCLUSIONS: Prescribers were adherent to a 5-day delay in the initiation of ESA
      therapy policy which resulted in a reduction in ESA usage, did not impact the
      discharge Hb levels, and was proven to be cost effective.

PMID- 29182649
TI  - Men's perspectives of prostate cancer screening: A systematic review of
      qualitative studies.
AB  - BACKGROUND: Prostate cancer is the most commonly diagnosed non-skin cancer in
      men. Screening for prostate cancer is widely accepted; however concerns regarding
      the harms outweighing the benefits of screening exist. Although patient's play a
      pivotal role in the decision making process, men may not be aware of the
      controversies regarding prostate cancer screening. Therefore we aimed to describe
      men's attitudes, beliefs and experiences of prostate cancer screening. METHODS:
      Systematic review and thematic synthesis of qualitative studies on men's
      perspectives of prostate cancer screening. Electronic databases and reference
      lists were searched to October 2016. FINDINGS: Sixty studies involving 3,029 men
      aged from 18-89 years, who had been screened for prostate cancer by Prostate
      Specific Antigen (PSA) or Digital Rectal Examination (DRE) and not screened,
      across eight countries were included. Five themes were identified: Social
      prompting (trusting professional opinion, motivation from family and friends,
      proximity and prominence of cancer); gaining decisional confidence (overcoming
      fears, survival imperative, peace of mind, mental preparation, prioritising
      wellbeing); preserving masculinity (bodily invasion, losing sexuality,
      threatening manhood, medical avoidance); avoiding the unknown and uncertainties
      (taboo of cancer-related death, lacking tangible cause, physiological and
      symptomatic obscurity, ambiguity of the procedure, confusing controversies); and
      prohibitive costs. CONCLUSIONS: Men are willing to participate in prostate cancer
      screening to prevent cancer and gain reassurance about their health, particularly
      when supported or prompted by their social networks or healthcare providers.
      However, to do so they needed to mentally overcome fears of losing their
      masculinity and accept the intrusiveness of screening, the ambiguities about the
      necessity and the potential for substantial costs. Addressing the concerns and
      priorities of men may facilitate informed decisions about prostate cancer
      screening and improve patient satisfaction and outcomes.

PMID- 29182651
TI  - Evidence of increased toxic Alexandrium tamarense dinoflagellate blooms in the
      eastern Bering Sea in the summers of 2004 and 2005.
AB  - The eastern Bering Sea has a vast continental shelf, which contains various
      endangered marine mammals and large fishery resources. Recently, high numbers of
      toxic A. tamarense resting cysts were found in the bottom sediment surface of the
      eastern Bering Sea shelf, suggesting that the blooms have recently occurred.
      However, little is known about the presence of A. tamarense vegetative cells in
      the eastern Bering Sea. This study's goals were to detect the occurrence of A.
      tamarense vegetative cells on the eastern Bering Sea shelf and to find a
      relationship between environmental factors and their presence. Inter-annual field
      surveys were conducted to detect A. tamarense cells and environmental factors,
      such as nutrients, salinity, chlorophyll a, and water temperature, along a
      transect line on the eastern Bering Sea shelf during the summers of 2004, 2005,
      2006, 2009, 2012, and 2013. A. tamarense vegetative cells were detected during
      every sampling year, and their quantities varied greatly from year to year. The
      maximum cell densities of A. tamarense observed during the summers of 2004 and
      2005 were much higher than the Paralytic shellfish poisoning warning levels,
      which are greater than 100-1,000 cells L-1, in other subarctic areas. Lower
      quantities of the species occurred during the summers of 2009, 2012, and 2013. A
      significant positive correlation between A. tamarense quantity and water
      temperature and significant negative correlations between A. tamarense quantity
      and nutrient concentrations (of phosphate, silicate, and nitrite and nitrate)
      were detected in every sampling period. The surface- and bottom-water
      temperatures varied significantly from year to year, suggesting that water
      temperatures, which have been known to affect the cell growth and cyst
      germination of A. tamarense, might have affected the cells' quantities in the
      eastern Bering Sea each summer. Thus, an increase in the Bering Sea shelf's water
      temperature during the summer will increase the frequency and scale of toxic
      blooms and the toxin contamination of plankton feeders. This poses serious
      threats to humans and the marine ecosystem.

PMID- 29182652
TI  - Primary care and health inequality: Difference-in-difference study comparing
      England and Ontario.
AB  - BACKGROUND: It is not known whether equity-oriented primary care investment that
      seeks to scale up the delivery of effective care in disadvantaged communities can
      reduce health inequality within high-income settings that have pre-existing
      universal primary care systems. We provide some non-randomised controlled
      evidence by comparing health inequality trends between two similar jurisdictions
      one of which implemented equity-oriented primary care investment in the mid-to
      late 2000s as part of a cross-government strategy for reducing health inequality
      (England), and one which invested in primary care without any explicit equity
      objective (Ontario, Canada). METHODS: We analysed whole-population data on 32,482
      neighbourhoods (with mean population size of approximately 1,500 people) in
      England, and 18,961 neighbourhoods (with mean population size of approximately
      700 people) in Ontario. We examined trends in mortality amenable to healthcare by
      decile groups of neighbourhood deprivation within each jurisdiction. We used
      linear models to estimate absolute and relative gaps in amenable mortality
      between most and least deprived groups, considering the gradient between these
      extremes, and evaluated difference-in-difference comparisons between the two
      jurisdictions. RESULTS: Inequality trends were comparable in both jurisdictions
      from 2004-6 but diverged from 2007-11. Compared with Ontario, the absolute gap in
      amenable mortality in England fell between 2004-6 and 2007-11 by 19.8 per 100,000
      population (95% CI: 4.8 to 34.9); and the relative gap in amenable mortality fell
      by 10 percentage points (95% CI: 1 to 19). The biggest divergence occurred in the
      most deprived decile group of neighbourhoods. DISCUSSION: In comparison to
      Ontario, England succeeded in reducing absolute socioeconomic gaps in mortality
      amenable to healthcare from 2007 to 2011, and preventing them from growing in
      relative terms. Equity-oriented primary care reform in England in the mid-to-late
      2000s may have helped to reduce socioeconomic inequality in health, though other
      explanations for this divergence are possible and further research is needed on
      the specific causal mechanisms.

PMID- 29182653
TI  - Recovery from trauma induced amnesia correlates with normalization of thrombin
      activity in the mouse hippocampus.
AB  - Transient amnesia is a common consequence of minimal traumatic brain injury
      (mTBI). However, while recent findings have addressed the mechanisms involved in
      its onset, the processes contributing to its recovery have not yet been
      addressed. Recently, we have found that thrombin is detected at high
      concentrations in the brain of mice after exposure to mTBI and that in such
      settings amnesia is rescued by either inhibiting thrombin activity or by blockade
      of PAR1. Here, we report that mice spontaneously recover from amnesia after two
      weeks from mTBI exposure. At this time point, long term potentiation was equally
      evoked in injured vs. control animals with thrombin concentration in the brain
      being normalized at this stage. These findings, which refer to the specific
      aspect of memory retrieval upon mTBI, together with our previous work, hint to a
      strong correlation between cognitive defects in the context of mTBI and thrombin
      concentrations in the brain. This may suggest that a possible scavenging of
      thrombin in the brain at early phases following mTBI may improve memory function.

PMID- 29182654
TI  - Knowledge, attitudes and behaviours of women regarding breast and cervical cancer
      in Malatya, Turkey.
AB  - The aim of this study is to gather information about the knowledge, attitudes and
      behaviours of women regarding breast and cervical cancer, to increase the
      knowledge level of the relevant age group and to begin including the relevant age
      group in screening programs. This cross-sectional study is composed of 6910 women
      aged 30-69 years in Malatya, Turkey. The study aimed to reach 1782 women with a
      survey, and all of them were reached. The questionnaire form was completed with
      face-to-face interview. For statistical analysis, data were evaluated as number
      and percentage distributions. The average age of the women was 45.6+/-11.4.
      Nearly half of the women (46.4%) did not know that scans for early detection of
      breast and cervical cancers were free. Only 22.2% of women knew that breast
      cancer could be diagnosed early by mammography. 72.7% had never received a
      mammogram. One third (31.6%) of women did not know it was possible to recognize
      cervical cancer early, and two thirds (64.5%) of women had not received a Pap
      smear test. It has been determined that Turkish women do not have adequate
      knowledge about cancer diagnosis, early cancer diagnosis, and screening.

PMID- 29182655
TI  - A mechanistic model for spread of livestock-associated methicillin-resistant
      Staphylococcus aureus (LA-MRSA) within a pig herd.
AB  - Before an efficient control strategy for livestock-associated methicillin
      resistant Staphylococcus aureus (LA-MRSA) in pigs can be decided upon, it is
      necessary to obtain a better understanding of how LA-MRSA spreads and persists
      within a pig herd, once it is introduced. We here present a mechanistic
      stochastic discrete-event simulation model for spread of LA-MRSA within a farrow
      to-finish sow herd to aid in this. The model was individual-based and included
      three different disease compartments: susceptible, intermittent or persistent
      shedder of MRSA. The model was used for studying transmission dynamics and within
      farm prevalence after different introductions of LA-MRSA into a farm. The spread
      of LA-MRSA throughout the farm mainly followed the movement of pigs. After spread
      of LA-MRSA had reached equilibrium, the prevalence of LA-MRSA shedders was
      predicted to be highest in the farrowing unit, independent of how LA-MRSA was
      introduced. LA-MRSA took longer to spread to the whole herd if introduced in the
      finisher stable, rather than by gilts in the mating stable. The more LA-MRSA
      positive animals introduced, the shorter time before the prevalence in the herd
      stabilised. Introduction of a low number of intermittently shedding pigs was
      predicted to frequently result in LA-MRSA fading out. The model is a potential
      decision support tool for assessments of short and long term consequences of
      proposed intervention strategies or surveillance options for LA-MRSA within pig
      herds.

PMID- 29182656
TI  - Assessment of the prognostic value of the 8th AJCC staging system for patients
      with clinically staged prostate cancer; A time to sub-classify stage IV?
AB  - BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system (8th
      edition) for prostate cancer has been published. The current study seeks to
      validate the prognostic performance of the changes in the new system among
      clinically staged prostate cancer patients registered within the surveillance,
      epidemiology and end results (SEER) database. METHODS: SEER database (2004-2014)
      has been accessed through SEER*Stat program and AJCC 7th and 8th edition stages
      were calculated utilizing T, N and M stages as well as baseline prostatic
      specific antigen (PSA) and grade group. Cancer-specific and overall survival
      analyses according to 6th, 7th and 8th editions were conducted through Kaplan
      Meier analysis. Moreover, multivariate analysis was conducted through a Cox
      proportional hazard model. RESULTS: A total of 110499 patients with prostate
      cancer were identified in the period from 2004-2014.For cancer- specific survival
      according to 8th AJCC, all pair wise P values for comparison were significant
      (<0.01) except for stage IIA vs. IIB; while for overall survival according to 8th
      AJCC, all pair wise P values for comparison were significant (<0.02) except for
      stage IIIA vs. IIIB. Results of c-index assessment for cancer-specific survival
      for the three AJCC editions were as follows: c-index for AJCC 6th edition was
      0.816; c-index for AJCC 7th edition was 0.897; c-index for AJCC 8th edition was
      0.907. For stage IVB prostate cancer (i.e.M1 disease), further sub-staging was
      proposed according to M1 sub-stage (i.e. M1a, M1b and M1c). Pair wise comparison
      between these proposed sub-stages was conducted for both cancer-specific and
      overall survival. For both cancer-specific and overall survival, all pair wise P
      values for comparisons were <0.0001. CONCLUSION: Compared to older staging
      systems (6th and 7th), the 8th system is more discriminatory. Further sub
      classification of stage IV disease is suggested.

PMID- 29182657
TI  - Accuracy and reproducibility of CT right-to-left ventricular diameter measurement
      in patients with acute pulmonary embolism.
AB  - BACKGROUND: Right ventricular (RV) dysfunction caused by acute pulmonary embolism
      (PE) is associated with poor short- and long-term prognosis. RV dilatation as a
      proxy for RV dysfunction can be assessed by calculating the right-to-left
      ventricle diameter (RV/LV) ratio on standard computed tomography pulmonary
      angiography (CTPA) images. It is unknown whether dedicated training is required
      to accurately and reproducibly measure RV/LV ratio therefore we aimed to assess
      these parameters in residents in internal medicine without experience in CTPA
      reading. METHODS: CTPA images of 100 patients with PE were assessed by three
      residents after single instruction, and one experienced thoracic radiologist.
      Maximum diameters were evaluated in the axial view by measuring the distance
      between the ventricular endocardium and the interventricular septum,
      perpendicular to the long axis of the heart. RV dilatation was defined as a ratio
      of >=1.0. Interobserver accuracy and reproducibility was determined using Kappa
      statistics, Bland-Altman analysis and Spearman's rank correlation. RESULTS: The
      kappa statistic for the presence of RV dilatation of the residents compared to
      the experienced radiologist ranged from 0.83-0.94. The average interobserver
      difference in calculated RV/LV ratio's (+/-SD) between the three residents was: 
      0.01 (SD0.11), 0.07 (SD0.14) and 0.06 (SD0.18) with an overall mean RV/LV
      diameter ratio of 1.04. In line with this, Spearman's rank correlation
      coefficients were 0.92, 0.88 and 0.85 respectively indicating very good
      correlation (p<0.01 for all). CONCLUSION: After simple instruction, RV/LV
      diameter ratio assessment on CTPA images by clinical residents is accurate and
      reproducible, which is of help in identifying PE patients at risk.

PMID- 29182658
TI  - High-permeability region size on perfusion CT predicts hemorrhagic transformation
      after intravenous thrombolysis in stroke.
AB  - OBJECTIVE: Blood-brain barrier (BBB) permeability has been proposed as a
      predictor of hemorrhagic transformation (HT) after tissue plasminogen activator
      (tPA) administration; however, the reliability of perfusion computed tomography
      (PCT) permeability imaging for predicting HT is uncertain. We aimed to determine
      the performance of high-permeability region size on PCT (HPrs-PCT) in predicting
      HT after intravenous tPA administration in patients with acute stroke. METHODS:
      We performed a multimodal CT protocol (non-contrast CT, PCT, CT angiography) to
      prospectively study patients with middle cerebral artery occlusion treated with
      tPA within 4.5 hours of symptom onset. HT was graded at 24 hours using the
      European-Australasian Acute Stroke Study II criteria. ROC curves selected optimal
      volume threshold, and multivariate logistic regression analysis identified
      predictors of HT. RESULTS: The study included 156 patients (50% male, median age
      75.5 years). Thirty-seven (23,7%) developed HT [12 (7,7%), parenchymal hematoma
      type 2 (PH-2)]. At admission, patients with HT had lower platelet values, higher
      NIHSS scores, increased ischemic lesion volumes, larger HPrs-PCT, and poorer
      collateral status. The negative predictive value of HPrs-PCT at a threshold of
      7mL/100g/min was 0.84 for HT and 0.93 for PH-2. The multiple regression analysis
      selected HPrs-PCT at 7mL/100g/min combined with platelets and baseline NIHSS
      score as the best model for predicting HT (AUC 0.77). HPrs-PCT at 7mL/100g/min
      was the only independent predictor of PH-2 (OR 1, AUC 0.68, p = 0.045).
      CONCLUSIONS: HPrs-PCT can help predict HT after tPA, and is particularly useful
      in identifying patients at low risk of developing HT.

PMID- 29182659
TI  - Fractal analyses reveal independent complexity and predictability of gait.
AB  - Locomotion is a natural task that has been assessed for decades and used as a
      proxy to highlight impairments of various origins. So far, most studies adopted
      classical linear analyses of spatio-temporal gait parameters. Here, we use more
      advanced, yet not less practical, non-linear techniques to analyse gait time
      series of healthy subjects. We aimed at finding more sensitive indexes related to
      spatio-temporal gait parameters than those previously used, with the hope to
      better identify abnormal locomotion. We analysed large-scale stride interval time
      series and mean step width in 34 participants while altering walking direction
      (forward vs. backward walking) and with or without galvanic vestibular
      stimulation. The Hurst exponent alpha and the Minkowski fractal dimension D were
      computed and interpreted as indexes expressing predictability and complexity of
      stride interval time series, respectively. These holistic indexes can easily be
      interpreted in the framework of optimal movement complexity. We show that alpha
      and D accurately capture stride interval changes in function of the experimental
      condition. Walking forward exhibited maximal complexity (D) and hence,
      adaptability. In contrast, walking backward and/or stimulation of the vestibular
      system decreased D. Furthermore, walking backward increased predictability
      (alpha) through a more stereotyped pattern of the stride interval and galvanic
      vestibular stimulation reduced predictability. The present study demonstrates the
      complementary power of the Hurst exponent and the fractal dimension to improve
      walking classification. Our developments may have immediate applications in
      rehabilitation, diagnosis, and classification procedures.

PMID- 29182661
TI  - Classical and next generation sequencing approaches unravel Bymovirus diversity
      in barley crops in France.
AB  - Despite the generalized use of cultivars carrying the rym4 resistance gene, the
      impact of viral mosaic diseases on winter barleys increased in recent years in
      France. This change could reflect i) an increased prevalence of the rym4
      resistance-breaking pathotype of Barley yellow mosaic virus Y (BaYMV-2), ii) the
      emergence of rym4 resistance-breaking pathotypes of Barley mild mosaic virus
      (BaMMV) or iii) the emergence of other viruses. A study was undertaken to
      determine the distribution and diversity of viruses causing yellow mosaic
      disease. A collection of 241 symptomatic leaf samples from susceptible, rym4 and
      rym5 varieties was gathered from 117 sites. The viruses present in all samples
      were identified by specific RT-PCR assays and, for selected samples, by double
      stranded RNA next-generation sequencing (NGS). The results show that BaYMV-2 is
      responsible for the symptoms observed in varieties carrying the resistance gene
      rym4. In susceptible varieties, both BaYMV-1 and BaYMV-2 were detected, together
      with BaMMV. Phylogenetic analyses indicate that the rym4 resistance-breaking
      ability independently evolved in multiple genetic backgrounds. Parallel analyses
      revealed a similar scenario of multiple independent emergence events in BaMMV for
      rym5 resistance-breaking, likely involving multiple amino acid positions in the
      viral-linked genome protein. NGS analyses and classical techniques provided
      highly convergent results, highlighting and validating the power of NGS
      approaches for diagnostics and viral population characterization.

PMID- 29182660
TI  - Interaction between TCF7L2 polymorphism and dietary fat intake on high density
      lipoprotein cholesterol.
AB  - Recent evidence suggests that lifestyle factors influence the association between
      the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2)
      gene variants and cardio-metabolic traits in several populations; however, the
      available research is limited among the Asian Indian population. Hence, the
      present study examined whether the association between the MC4R single nucleotide
      polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and
      rs7903146) and cardio-metabolic traits is modified by dietary factors and
      physical activity. This cross sectional study included a random sample of normal
      glucose tolerant (NGT) (n = 821) and participants with type 2 diabetes (T2D) (n =
      861) recruited from the urban part of the Chennai Urban Rural Epidemiology Study
      (CURES). A validated food frequency questionnaire (FFQ) was used for dietary
      assessment and self-reported physical activity measures were collected. The
      threshold for significance was set at P = 0.00023 based on Bonferroni correction
      for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors)].
      After Bonferroni correction, there was a significant interaction between the
      TCF7L2 rs12255372 SNP and fat intake (g/day) (Pinteraction = 0.0001) on high
      density lipoprotein cholesterol (HDL-C), where the 'T' allele carriers in the
      lowest tertile of total fat intake had higher HDL-C (P = 0.008) and those in the
      highest tertile (P = 0.017) had lower HDL-C compared to the GG homozygotes. In a
      secondary analysis of SNPs with the subtypes of fat, there was also a significant
      interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA,
      g/day) (Pinteraction<0.0001) on HDL-C, where the minor allele carriers had higher
      HDL-C in the lowest PUFA tertile (P = 0.024) and those in the highest PUFA
      tertile had lower HDL-C (P = 0.028) than GG homozygotes. In addition, a
      significant interaction was also seen between TCF7L2 SNP rs12255372 and fibre
      intake (g/day) on HDL-C (Pinteraction<0.0001). None of the other interactions
      between the SNPs and lifestyle factors were statistically significant after
      correction for multiple testing. Our findings indicate that the association
      between TCF7L2 SNP rs12255372 and HDL-C may be modified by dietary fat intake in
      this Asian Indian population.

PMID- 29182662
TI  - Threats from urban expansion, agricultural transformation and forest loss on
      global conservation priority areas.
AB  - Including threats in spatial conservation prioritization helps identify areas for
      conservation actions where biodiversity is at imminent risk of extinction. At the
      global level, an important limitation when identifying spatial priorities for
      conservation actions is the lack of information on the spatial distribution of
      threats. Here, we identify spatial conservation priorities under three prominent
      threats to biodiversity (residential and commercial development, agricultural
      expansion, and forest loss), which are primary drivers of habitat loss and
      threaten the persistence of the highest number of species in the International
      Union for the Conservation of Nature (IUCN) Red List, and for which spatial data
      is available. We first explore how global priority areas for the conservation of
      vertebrate (mammals, birds, and amphibians) species coded in the Red List as
      vulnerable to each threat differ spatially. We then identify spatial conservation
      priorities for all species vulnerable to all threats. Finally, we identify the
      potentially most threatened areas by overlapping the identified priority areas
      for conservation with maps for each threat. We repeat the same with four other
      well-known global conservation priority area schemes, namely Key Biodiversity
      Areas, Biodiversity Hotspots, the global Protected Area Network, and Wilderness
      Areas. We find that residential and commercial development directly threatens
      only about 4% of the global top 17% priority areas for species vulnerable under
      this threat. However, 50% of the high priority areas for species vulnerable to
      forest loss overlap with areas that have already experienced some forest loss.
      Agricultural expansion overlapped with ~20% of high priority areas. Biodiversity
      Hotspots had the greatest proportion of their total area under direct threat from
      all threats, while expansion of low intensity agriculture was found to pose an
      imminent threat to Wilderness Areas under future agricultural expansion. Our
      results identify areas where limited resources should be allocated to mitigate
      risks to vertebrate species from habitat loss.

PMID- 29182663
TI  - Inattention in primary school is not good for your future school achievement-A
      pattern classification study.
AB  - Inattention in childhood is associated with academic problems later in life. The
      contribution of specific aspects of inattentive behaviour is, however, less
      known. We investigated feature importance of primary school teachers' reports on
      nine aspects of inattentive behaviour, gender and age in predicting future
      academic achievement. Primary school teachers of n = 2491 children (7-9 years)
      rated nine items reflecting different aspects of inattentive behaviour in 2002. A
      mean academic achievement score from the previous semester in high school (2012)
      was available for each youth from an official school register. All scores were at
      a categorical level. Feature importances were assessed by using multinominal
      logistic regression, classification and regression trees analysis, and a random
      forest algorithm. Finally, a comprehensive pattern classification procedure using
      k-fold cross-validation was implemented. Overall, inattention was rated as more
      severe in boys, who also obtained lower academic achievement scores in high
      school than girls. Problems related to sustained attention and distractibility
      were together with age and gender defined as the most important features to
      predict future achievement scores. Using these four features as input to a
      collection of classifiers employing k-fold cross-validation for prediction of
      academic achievement level, we obtained classification accuracy, precision and
      recall that were clearly better than chance levels. Primary school teachers'
      reports of problems related to sustained attention and distractibility were
      identified as the two most important features of inattentive behaviour predicting
      academic achievement in high school. Identification and follow-up procedures of
      primary school children showing these characteristics should be prioritised to
      prevent future academic failure.

PMID- 29182664
TI  - Differential inhibitory and activating NK cell receptor levels and NK/NKT-like
      cell functionality in chronic and recovered stages of chikungunya.
AB  - The role of natural killer (NK; CD3-CD56+)/NKT (CD3+CD56+)-like cells in
      chikungunya virus (CHIKV) disease progression/recovery remains unclear. Here, we
      investigated the expression profiles and function of NK and NKT-like cells from
      35 chronic chikungunya patients, 30 recovered individuals, and 69 controls.
      Percentage of NKT-like cells was low in chronic chikungunya patients. NKp30+,
      CD244+, DNAM-1+, and NKG2D+ NK cell percentages were also lower (MFI and/or
      percentage), while those of CD94+ and NKG2A+ NKT-like cells were higher (MFI
      and/or percentage) in chronic patients than in recovered subjects. IFN-gamma and
      TNF-alpha expression on NKT-like cells was high in the chronic patients, while
      only IFN-gamma expression on NK cells was high in the recovered individuals.
      Furthermore, percentage of perforin+NK cells was low in the chronic patients.
      Lower cytotoxic activity was observed in the chronic patients than in the
      controls. CD107a expression on NK and NKT-like cells post anti-CD94/anti-NKG2A
      blocking was comparable among the patients and controls. Upregulated inhibitory
      and downregulated activating NK receptor expressions on NK/NKT-like cells, lower
      perforin+ and CD107a+NK cells are likely responsible for inhibiting the NK and
      NKT-like cell function in the chronic stage of chikungunya. Therefore,
      deregulation of NKR expression might underlie CHIKV-induced chronicity.

PMID- 29182665
TI  - The role of protease inhibitors on the remineralization of demineralized dentin
      using the PILP method.
AB  - Mineralized and sound dentin matrices contain inactive preforms of proteolytic
      enzymes that may be activated during the demineralization cycle. In this study,
      we tested the hypothesis that protease inhibitors (PI) preserve demineralized
      collagen fibrils and other constituents of the dentin matrix and thereby affect
      the potential for remineralization. Artificial carious lesions with lesion depths
      of 140 MUm were created with acetate buffer (pH = 5.0, 66 hours), and
      remineralized using a polymer-induced-liquid-precursor (PILP) process (pH = 7.4,
      14 days) containing poly(aspartic acid) (pAsp) as the process-directing agent. De
      and remineralizing procedures were performed in the presence or absence of PI.
      Ultrastructure and mechanical recovery of demineralized dentin following PILP
      remineralization were examined and measured in water with atomic force microscopy
      (AFM) and nanoindentation. Nanomechanical properties of hydrated artificial
      lesions had a low elastic modulus (ER <0.4 GPa) extending about 100 MUm into the
      lesion, followed by a sloped region of about 140 MUm depth where values reached
      those of normal dentin (18.0-20.0 GPa). Mapping of mineral content by both micro
      FTIR and micro x-ray computed tomography correlated well with modulus profiles
      obtained by nanoindentation. Tissue demineralized in the presence of PI exhibited
      higher elastic moduli (average 2.8 GPa) across the lesion and comprised a narrow
      zone in the outer lesion with strongly increased modulus (up to 8 GPa; p < 0.05),
      which might be related to the preservation of non-collagenous proteins that
      appear to induce calcium phosphate mineral formation even under demineralizing
      physical-chemical conditions. However, mechanical aspects of remineralization
      through the elastic modulus change, and the micromorphological aspects with SEM
      and TEM observation were almost identical with PILP treatments being conducted in
      the presence or absence of PI. Thus, the application of the protease inhibitors
      (PI) seemed to be less effective in promoting the remineralization of
      demineralized dentin.

PMID- 29182666
TI  - GnRH receptor gene mutations in adolescents and young adults presenting with
      signs of partial gonadotropin deficiency.
AB  - Biallelic, partial loss-of-function mutations in GNRHR cause a wide spectrum of
      reproductive phenotypes from constitutional delay of growth and puberty to
      complete congenital hypogonadotropic hypogonadism. We studied the frequency of
      GNRHR, FGFR1, TAC3, and TACR3 mutations in nine adolescent and young adult
      females with clinical cues consistent with partial gonadotropin deficiency
      (stalled puberty, unexplained secondary amenorrhea), and describe phenotypic
      features and molecular genetic findings of monozygotic twin brothers with stalled
      puberty. Two girls out of nine (22%, 95%CI 6-55%) carried biallelic mutations in
      GNRHR. The girl with compound heterozygous c.317A>G p.(Gln106Arg) and
      c.924_926delCTT p.(Phe309del) GNRHR mutations displayed incomplete puberty and
      clinical signs of hypoestrogenism. The patient carrying a homozygous c.785G>A
      p.(Arg262Gln) mutation presented with signs of hypoestrogenism and unexplained
      secondary amenorrhea. None of the patients exhibited mutations in FGFR1, TAC3, or
      TACR3. The twin brothers, compound heterozygous for GNRHR mutations c.317A>G
      p.(Gln106Arg) and c.785G>A p.(Arg262Gln), presented with stalled puberty and were
      discordant for weight, and the heavier of them had lower testosterone levels.
      These results suggest that genetic testing of the GNRHR gene should be offered to
      adolescent females with low-normal gonadotropins and unexplained stalled puberty
      or menstrual dysfunction. In male patients with partial gonadotropin deficiency,
      excess adipose tissue may suppress hypothalamic-pituitary-gonadal axis.

PMID- 29182667
TI  - Heat shock proteins HSPB8 and DNAJC5B have HCV antiviral activity.
AB  - Hepatitis C is a disease caused by the hepatitis C virus (HCV), and an estimated
      3% of the world population is infected with the virus. During replication, HCV
      interacts with several cellular proteins. Studies have shown that several heat
      shock proteins (HSPs) have an altered expression profile in the presence of the
      virus, and some HSPs interact directly with HCV proteins. In the present study,
      we evaluated the expression levels of heat shock proteins in vitro in the
      presence and absence of HCV. The differential expression of 84 HSPs and
      chaperones was observed using a qPCR array, comparing HCV uninfected and infected
      Huh7.5 cells. To validate qPCR array, the differentially expressed genes were
      tested by real-time PCR in three different HCV models: subgenomic HCV replicon
      cells (SGR-JFH-1), JFH-1 infected cells (both genotype 2a) and subgenomic S52
      cells (genotype 3). The HSPB8 gene showed increased expression in all three viral
      models. We silenced HSPB8 expression and observed an increase in viral
      replication. In contrast, when we increased the expression of HSPB8, a decrease
      in the HCV replication rate was observed. The same procedure was adopted for
      DNAJC5B, and HCV showed a similar replication pattern as that observed for HSPB8.
      These results suggest that HSPB8 may act as an intracellular factor against
      hepatitis C virus replication and that DNAJC5B has the same function, with more
      relevant results for genotype 3. We also evaluated the direct interactions
      between HCV and HSP proteins, and the IP experiments showed that the HCV NS4B
      protein interacts with HSPB8. These results contribute to a better understanding
      of the mechanisms involved in HCV replication.

PMID- 29182668
TI  - Extracellular vesicles released by fibroblasts undergoing H-Ras induced
      senescence show changes in lipid profile.
AB  - Cells release extracellular vesicles (EVs) in their environment and cellular
      lipids play an important role in their formation, secretion and uptake. Besides,
      there is also evidence that EV transferred lipids impact on recipient's cell
      signaling. Cellular senescence is characterized by a state of permanent
      proliferation arrest and represents a barrier towards the development of
      neoplastic lesions. A peculiar feature of senescence is the release of many
      soluble factors, the so-called Senescence-Associated Secretory Phenotype, which
      play a key role in triggering paracrine senescence signals. Recently, evidences
      have suggested that this phenotype includes not only soluble factors, but also
      EVs. To identify lipid signatures associated with H-Ras-induced senescence in
      EVs, we expressed active H-Ras (H-RasV12) in human fibroblasts and investigated
      how it affects EV release and lipid composition. An enrichment of hydroxylated
      sphingomyelin, lyso- and ether-linked phospholipids and specific H-Ras-induced
      senescence signatures, e.g. sphingomyelin, lysophosphatidic acid and sulfatides,
      were found in EVs compared to cells. Furthermore, H-RasV12 expression in
      fibroblasts was associated with higher levels of tetraspanins involved in vesicle
      formation.

PMID- 29182671
TI  - Clustering of samples and variables with mixed-type data.
AB  - Analysis of data measured on different scales is a relevant challenge. Biomedical
      studies often focus on high-throughput datasets of, e.g., quantitative
      measurements. However, the need for integration of other features possibly
      measured on different scales, e.g. clinical or cytogenetic factors, becomes
      increasingly important. The analysis results (e.g. a selection of relevant genes)
      are then visualized, while adding further information, like clinical factors, on
      top. However, a more integrative approach is desirable, where all available data
      are analyzed jointly, and where also in the visualization different data sources
      are combined in a more natural way. Here we specifically target integrative
      visualization and present a heatmap-style graphic display. To this end, we
      develop and explore methods for clustering mixed-type data, with special focus on
      clustering variables. Clustering of variables does not receive as much attention
      in the literature as does clustering of samples. We extend the variables
      clustering methodology by two new approaches, one based on the combination of
      different association measures and the other on distance correlation. With
      simulation studies we evaluate and compare different clustering strategies.
      Applying specific methods for mixed-type data proves to be comparable and in many
      cases beneficial as compared to standard approaches applied to corresponding
      quantitative or binarized data. Our two novel approaches for mixed-type variables
      show similar or better performance than the existing methods ClustOfVar and bias
      corrected mutual information. Further, in contrast to ClustOfVar, our methods
      provide dissimilarity matrices, which is an advantage, especially for the purpose
      of visualization. Real data examples aim to give an impression of various kinds
      of potential applications for the integrative heatmap and other graphical
      displays based on dissimilarity matrices. We demonstrate that the presented
      integrative heatmap provides more information than common data displays about the
      relationship among variables and samples. The described clustering and
      visualization methods are implemented in our R package CluMix available from
      https://cran.r-project.org/web/packages/CluMix.

PMID- 29182669
TI  - NKT cells contribute to basal IL-4 production but are not required to induce
      experimental asthma.
AB  - CD1d-deficiency results in a selective deletion of NKT cells in mice that is
      reported to prevent murine allergic airway disease (AAD). Because we find 2-3
      fold lower basal IL-4 production in CD1d- mice than in wild-type (WT) mice, we
      hypothesized that the contribution made by NKT cells to AAD would depend on the
      strength of the stimulus used to induce the disease. Consequently, we compared
      CD1d-deficient mice to WT mice in the development of AAD, using several models of
      disease induction that differed in the type and dose of allergen, the site of
      sensitization and the duration of immunization. Surprisingly we found equivalent
      allergic inflammation and airway disease in WT and CD1d- mice in all models
      investigated. Consistent with this, NKT cells constituted only ~2% of CD4+ T
      cells in the lungs of mice with AAD, and IL-4-transcribing NKT cells did not
      expand with disease induction. Concerned that the congenital absence of NKT cells
      might have caused a compensatory shift within the immune response, we
      administered an anti-CD1d monoclonal Ab (mAb) to block NKT function before airway
      treatments, before or after systemic sensitization to antigen. Such Ab treatment
      did not affect disease severity. We suggest that the differences reported in the
      literature regarding the significance of NKT cells in the induction of allergic
      airway disease may have less to do with the methods used to study the disease and
      more to do with the animals themselves and/or the facilities used to house them.

PMID- 29182670
TI  - Diversity and potential activity of methanotrophs in high methane-emitting
      permafrost thaw ponds.
AB  - Lakes and ponds derived from thawing permafrost are strong emitters of carbon
      dioxide and methane to the atmosphere, but little is known about the methane
      oxidation processes in these waters. Here we investigated the distribution and
      potential activity of aerobic methanotrophic bacteria in thaw ponds in two types
      of eroding permafrost landscapes in subarctic Quebec: peatlands and mineral
      soils. We hypothesized that methanotrophic community composition and potential
      activity differ regionally as a function of the landscape type and permafrost
      degradation stage, and locally as a function of depth-dependent oxygen
      conditions. Our analysis of pmoA transcripts by Illumina amplicon sequencing and
      quantitative PCR showed that the communities were composed of diverse and
      potentially active lineages. Type I methanotrophs, particularly Methylobacter,
      dominated all communities, however there was a clear taxonomic separation between
      the two landscape types, consistent with environmental control of community
      structure. In contrast, methanotrophic potential activity, measured by pmoA
      transcript concentrations, did not vary with landscape type, but correlated with
      conductivity, phosphorus and total suspended solids. Methanotrophic potential
      activity was also detected in low-oxygen bottom waters, where it was inversely
      correlated with methane concentrations, suggesting methane depletion by
      methanotrophs. Methanotrophs were present and potentially active throughout the
      water column regardless of oxygen concentration, and may therefore be resilient
      to future mixing and oxygenation regimes in the warming subarctic.

PMID- 29182673
TI  - Ensemble machine learning and forecasting can achieve 99% uptime for rural
      handpumps.
AB  - Broken water pumps continue to impede efforts to deliver clean and economically
      viable water to the global poor. The literature has demonstrated that customers'
      health benefits and willingness to pay for clean water are best realized when
      clean water infrastructure performs extremely well (>99% uptime). In this paper,
      we used sensor data from 42 Afridev-brand handpumps observed for 14 months in
      western Kenya to demonstrate how sensors and supervised ensemble machine learning
      could be used to increase total fleet uptime from a best-practices baseline of
      about 70% to >99%. We accomplish this increase in uptime by forecasting pump
      failures and identifying existing failures very quickly. Comparing the costs of
      operating the pump per functional year over a lifetime of 10 years, we estimate
      that implementing this algorithm would save 7% on the levelized cost of water
      relative to a sensor-less scheduled maintenance program. Combined with a rigorous
      system for dispatching maintenance personnel, implementing this algorithm in a
      real-world program could significantly improve health outcomes and customers'
      willingness to pay for water services.

PMID- 29182672
TI  - Increased expression of Th17 cytokines and interleukin-22 correlates with disease
      activity in pristane-induced arthritis in rats.
AB  - The objective of this study was to identify the key changed subtype of T helper
      cells (Th cells) and their cytokines in pristane-induced arthritis (PIA) in rats.
      The severity of arthritis was evaluated by body weight, clinical score, the
      perimeter of ankle and mid-paw and histological assessment of ankle joints.
      Cytokines of Th1, Th2 and Th17 were determined in the spleen and inguinal lymph
      nodes at 28 days after pristane injection by real-time qPCR. The mRNA levels of
      IL-22 receptors, IL-22R1 and IL-22BP, in the spleen were quantified by real-time
      qPCR. Additionally, IL-22 expression in synovial membrane was detected by Western
      blotting, and serum IL-22 concentration was determined by ELISA. Correlation
      between IL-22 concentration and clinical score was analyzed. By screening the
      cytokines of Th1, Th2 and Th17 expression profile, we found that the mRNA levels
      of Th17 cytokines were significantly increased in PIA rats. Particularly, a
      significant increase in the protein expression of IL-22 was determined in
      synovial membrane and serum from PIA rats, and correlated with clinical score. We
      conclude that IL-22 expression level was increased and correlated with disease
      severity, which indicated that IL-22 may play an important role in development of
      PIA, and was helpful to explorer the pathogenesis of rheumatoid arthritis.

PMID- 29182674
TI  - Genome-wide analysis of the diversity and ancestry of Korean dogs.
AB  - There are various hypotheses on dog domestication based on archeological and
      genetic studies. Although many studies have been conducted on the origin of dogs,
      the existing literature about the ancestry, diversity, and population structure
      of Korean dogs is sparse. Therefore, this study is focused on the origin,
      diversity and population structure of Korean dogs. The study sample comprised
      four major categories, including non-dogs (coyotes and wolves), ancient, modern
      and Korean dogs. Selected samples were genotyped using an Illumina CanineHD array
      containing 173,662 single nucleotide polymorphisms. The genome-wide data were
      filtered using quality control parameters in PLINK 1.9. Only autosomal
      chromosomes were used for further analysis. The negative off-diagonal variance of
      the genetic relationship matrix analysis depicted, the variability of samples in
      each population. FIS (inbreeding rate within a population) values indicated, a
      low level of inbreeding within populations, and the patterns were in concordance
      with the results of Nei's genetic distance analysis. The lowest FST (inbreeding
      rate between populations) values among Korean and Chinese breeds, using a
      phylogenetic tree, multi-dimensional scaling, and a TreeMix likelihood tree
      showed Korean breeds are highly related to Chinese breeds. The Korean breeds
      possessed a unique and large diversity of admixtures compared with other breeds.
      The highest and lowest effective population sizes were observed in Korean Jindo
      Black (485) and Korean Donggyeong White (109), respectively. The historical
      effective population size of all Korean dogs showed declining trend from the past
      to present. It is important to take immediate action to protect the Korean dog
      population while conserving their diversity. Furthermore, this study suggests
      that Korean dogs have unique diversity and are one of the basal lineages of East
      Asian dogs, originating from China.

PMID- 29182675
TI  - An analytical approach to sparse telemetry data.
AB  - Horizontal behavior of highly migratory marine species is difficult to decipher
      because animals are wide-ranging, spend minimal time at the ocean surface, and
      utilize remote habitats. Satellite telemetry enables researchers to track
      individual movements, but population level inferences are rare due to data
      limitations that result from difficulty of capture and sporadic tag reporting. We
      introduce a Bayesian modeling framework to address population level questions
      with satellite telemetry data when data are sparse. We also outline an approach
      for identifying informative variables for use within the model. We tested our
      modeling approach using a large telemetry dataset for Shortfin Makos (Isurus
      oxyrinchus), which allowed us to assess the effects of various degrees of data
      paucity. First, a permuted Random Forest analysis is implemented to determine
      which variables are most informative. Next, a generalized additive mixed model is
      used to help define the relationship of each remaining variable with the response
      variable. Using jags and rjags for the analysis of Bayesian hierarchical models
      using Markov Chain Monte Carlo simulation, we then developed a movement model to
      generate parameter estimates for each of the variables of interest. By randomly
      reducing the tagging dataset by 25, 50, 75, and 90 percent and recalculating the
      parameter estimates, we demonstrate that the proposed Bayesian approach can be
      applied in data-limited situations. We also demonstrate how two commonly used
      linear mixed models with maximum likelihood estimation (MLE) can be similarly
      applied. Additionally, we simulate data from known parameter values to test each
      model's ability to recapture those values. Despite performing similarly, we
      advocate using the Bayesian over the MLE approach due to the ability for later
      studies to easily utilize results of past study to inform working models, and the
      ability to use prior knowledge via informed priors in systems where such
      information is available.

PMID- 29182676
TI  - Reproductive isolation in the acoustically divergent groups of tettigoniid,
      Mecopoda elongata.
AB  - Sympatric divergent populations of the same species provide an opportunity to
      study the evolution and maintenance of reproductive isolation. Male mating calls
      are important in sexual selection in acoustically communicating species, and they
      also have the potential to maintain isolation among species or incipient species.
      We studied divergent south Indian populations of the bush cricket Mecopoda
      elongata which are extremely difficult to distinguish morphologically, but which
      exhibit striking divergence in male acoustic signals. We performed phonotactic
      experiments investigating the relative preference of females of the "Chirper"
      song type for calls of all 5 of the song types found in the region (in varying
      degrees of sympatry). We found that Chirper females preferred their own song type
      and were completely unresponsive to three trilling song types. Chirper females
      were occasionally attracted to the call type "Double Chirper" (the call most
      similar to their own type), suggesting call preference alone cannot provide a
      complete isolating mechanism. To investigate the basis of call preference we
      investigated the response of chirper females to variation in chirp rate. Chirper
      females responded most frequently to a mean chirp rate characteristic of their
      own song type rather than a higher chirp rate which would be more characteristic
      of the Double-Chirper song type. This suggests females drive stabilising
      selection on male chirp rate, which may contribute to the maintenance of
      isolation. Finally, a no-choice mating experiment using Chirper females and
      Chirper and Double Chirper males revealed a significant preference of Chirper
      females to mate with their own song type, even without a requirement for
      phonotaxis. Overall, the strong specificity of Chirper females for their 'own'
      song type provides evidence for behavioural isolation among divergent sympatric
      Mecopoda song types being maintained by female preference for both male song type
      and subsequent mating probability driven by other cues.

PMID- 29182677
TI  - Arabidopsis ubiquitin ligase PUB12 interacts with and negatively regulates Chitin
      Elicitor Receptor Kinase 1 (CERK1).
AB  - In Arabidopsis, fungal chitin is recognized as a pathogen-associated molecular
      pattern (PAMP) by the chitin receptor complex containing the lysin-motif (LysM)
      receptor-like kinases CERK1 and LYK5. Upon the perception of chitin, CERK1
      phosphorylates the receptor-like cytoplasmic kinase, PBL27, which activates the
      intracellular mitogen-activated protein kinase (MAPK) cascade. However, the
      mechanisms by which the CERK1-PBL27 complex is regulated remain largely unknown.
      We identified ubiquitin ligase PUB12 as a component of the PBL27 complex using co
      immunoprecipitation and mass spectrometry. However, PUB12 did not interact
      directly with PBL27. Instead, the ARM domains of PUB12 and its paralog PUB13
      interacted with the intracellular domain of CERK1 in a manner that was dependent
      on its autophosphorylation, suggesting that the phosphorylation-based auto
      activation of CERK1 may be required for its interaction with PUB12. The co
      expression of PUB12 in Nicotiana benthamiana reduced the accumulation of CERK1.
      The pub12 pub13 mutant exhibited enhanced chitin-induced immune responses such as
      ROS production, MAPK activation, and callose deposition. These results suggest
      that PUB12 and PUB13 are involved in the negative regulation of the chitin
      receptor complex, which may contribute to the transient desensitization of chitin
      induced responses.

PMID- 29182678
TI  - Diagnostic performance of point-of-care and central laboratory cardiac troponin
      assays in an emergency department.
AB  - Early diagnosis of myocardial infarction (MI) with cardiac troponin (cTn) assays
      at the point-of-care (POC) is suggested to shorten turn-around-time in the
      emergency department (ED). The present study aimed at comparing the diagnostic
      performance of two POC cTn assays with that of a central laboratory high
      sensitivity (hs) method, under routine ED conditions. In 2,163 non-selected ED
      patients suspected for MI, the diagnostic performance of the POC troponin I
      (TnI), troponin T (TnT), and hs-TnT assay for the prediction of MI was evaluated
      based on receiver operating characteristic (ROC) analyses and compared with the
      performance based on the manufacturers' cut-offs. Due to an observed association
      between renal function as determined by estimated glomerular filtration rate
      (eGFR) and cTn concentrations, all analyses were stratified by renal function. In
      patients with normal renal function (eGFR > 60 mL/min/1.73m2), POC and hs assays
      showed a comparable diagnostic performance as quantified by the area under the
      ROC curve (AUC) of about 0.88. The ROC-derived optimal cut-off (OCO) levels for
      the different cTn assays clearly changed with decreasing kidney function.
      Impaired kidney function required OCO to be three to five times higher to achieve
      a comparable performance. Particularly cTnT concentrations were strongly
      associated with renal function. The three cTn assays demonstrated equivalent
      diagnostic performance in ED-patients admitted with suspected ACS in relation to
      the release diagnosis, supporting the use of POC testing in this setting. The
      present results implicate that application of eGFR-specific OCOs may decrease
      false-positives among patients with impaired renal function. Providing individual
      cut-offs depending on patients' eGFR might be an appropriate add-on tool to
      improve specificity in the diagnosis of MI.

PMID- 29182679
TI  - The extracellular matrix protein Edil3 stimulates osteoblast differentiation
      through the integrin alpha5beta1/ERK/Runx2 pathway.
AB  - Epidermal growth factor-like repeats and discoidin I-like domain 3 (Edil3) is an
      extracellular matrix protein containing an Arg-Gly-Asp (RGD) motif that binds
      integrin. Recently, Edil3 has been implicated in various biological processes,
      including angiogenesis and cellular differentiation. It can inhibit inflammatory
      bone destruction. The objective of this study was to explore the role of Edil3 in
      osteoblast differentiation and its underlying molecular mechanisms. In wild-type
      mice, high expression levels of Edil3 mRNA were observed in isolated calvaria and
      tibia/femur bones. Immunohistochemical analysis showed that Edil3 protein was
      localized along periosteum and calcified regions surrounding bone tissues. When
      murine calvaria-derived MC3T3-E1 cells were cultured in osteogenic medium
      containing 50 MUg/ml ascorbic acid and 5 mM beta-glycerophosphate, Edil3 mRNA and
      protein expression levels were increased. Treatment with Edil3 protein in growth
      media increased expression levels of alkaline phosphatase and osteocalcin gene
      and phosphorylation level of extracellular signal-regulated kinase (ERK). Edil3
      treatment with osteogenic medium induced mineralization. Treatment with a
      neutralizing antibody against alpha5beta1 and MEK inhibitor U0126 inhibited Edil3
      enhanced osteogenic marker gene expression and mineral deposition. Edil3
      increased protein expression levels of transcription factor runt-related
      transcription factor2 (Runx2). Edil3-induced Runx2 protein expression was
      suppressed by pretreatment with U0126. Taken together, these results suggest that
      Edil3 may stimulate osteoblast differentiation and matrix mineralization by
      increasing expression of Runx2 through alpha5beta1 integrin /ERK pathway.

PMID- 29182681
TI  - Using 13C in cattle hair to trace back the maize level in the feeding regime-A
      field test.
AB  - Sections from cattle hair serve as an isotopic archive-they contain information
      on the cattle diet from different time periods. We tested the reliability of 13C
      signatures (delta13C) in cattle tail switch hair to retrospectively trace back
      the annual dietary proportion of maize of different production systems without
      having to sample and analyze the feed. Furthermore, we investigated if
      differences in dietary proportion of maize during summer and winter feeding can
      be detected in a single tail switch hair by sampling hair only once a year. We
      sampled hair and obtained information on management and annual composition of
      diets on 23 cattle farms in northern Germany. Farms differed in dietary
      proportions of maize, grass and concentrates as well as in grazing regime (year
      round grazing, summer grazing, no grazing). We found that the annual mean
      delta13C values (delta13CY) of two hair sections that contain the isotopic
      information of summer and winter feeding is a robust indicator for the annual
      proportion of maize in cattle diet on a farm. The grazing regimes could clearly
      be distinguished by analyzing seasonal mean delta13C values (delta13CS). We could
      also demonstrate short term changes in the diet changes by means of delta13CS. We
      conclude that the method can be used in different cattle production systems to
      check on dietary proportions of maize for a period of one year before sampling of
      hair.

PMID- 29182680
TI  - Differential activity of 2-methylene-19-nor vitamin D analogs on growth factor
      gene expression in rhino mouse skin and comparison to all-trans retinoic acid.
AB  - While all 2-methylene-19-nor analogs of 1alpha,25-dihydroxyvitamin D3
      (1alpha,25(OH)2D3) tested produce an increase in epidermal thickness in the rhino
      mouse, only a subset reduce utricle size (comedolysis). All-trans retinoic acid
      (atRA) also causes epidermal thickening and a reduction in utricle size in the
      rhino mouse. We now report that 2-methylene-19-nor-(20S)-1alpha
      hydroxybishomopregnacalciferol (2MbisP), a comedolytic analog, increases
      epidermal thickening more rapidly than does atRA, while both reduce utricle area
      at an equal rate. Whereas unlike atRA, 2MbisP does not alter the epidermal growth
      factor receptor ligand, heparin-binding epidermal growth factor-like growth
      factor, it does increase the expression of both amphiregulin and epigen mRNA,
      even after a single dose. In situ hybridization reveals an increase in these
      transcripts throughout the closing utricle as well as in the interfollicular
      epidermis. The mRNAs for other EGFR ligands including betacellulin and
      transforming growth factor-alpha, as well as the epidermal growth factor receptor
      are largely unaffected by 2MbisP. Another analog, 2-methylene-19-nor-(20S)-26,27
      dimethylene-1alpha,25-dihydroxyvitamin D3 (CAGE-3), produces epidermal thickening
      but fails to reduce utricle size or increase AREG mRNA levels. CAGE-3 modestly
      increases epigen mRNA levels, but only after 5 days of dosing. Thus, 2-MbisP
      produces unique changes in epidermal growth factor receptor ligand mRNAs that may
      be responsible for both epidermal proliferation and a reduction in utricle size.

PMID- 29182683
TI  - Principal component and discriminant analyses as powerful tools to support
      taxonomic identification and their use for functional and phylogenetic signal
      detection of isolated fossil shark teeth.
AB  - Identifying isolated teeth of fossil selachians only based on qualitative
      characters is sometimes hindered by similarity in their morphology, resulting
      often in heated taxonomic debates. On the other hand, the use of quantitative
      characters (i.e. measurements) has been often neglected or underestimated in
      characterization and identification of fossil teeth of selachians. Here we show
      that, employing a robust methodological protocol based on principal component and
      discriminant analyses on a sample of 175 isolated fossil teeth of lamniform
      sharks, the traditional morphometrics can be useful to support and complement the
      classic taxonomic identification made on qualitative features. Furthermore, we
      show that discriminant analysis can be successfully useful to assign
      indeterminate isolated shark teeth to a certain taxon. Finally, the degree of
      separation of the clusters might be used to predict functional and probably also
      phylogenetic signals in lamniform shark teeth. However, this needs to be tested
      in the future employing teeth of more extant and extinct lamniform sharks and it
      must be pointed out that this approach does not replace in any way the
      qualitative analysis, but it is intended to complement and support it.

PMID- 29182682
TI  - Inferior immunogenicity and efficacy of respiratory syncytial virus fusion
      protein-based subunit vaccine candidates in aged versus young mice.
AB  - Respiratory syncytial virus (RSV) is recognized as an important cause of lower
      and upper respiratory tract infections in older adults, and a successful vaccine
      would substantially lower morbidity and mortality in this age group. Recently,
      two vaccine candidates based on soluble purified glycoprotein F (RSV F), either
      alone or adjuvanted with glucopyranosyl lipid A formulated in a stable emulsion
      (GLA-SE), failed to reach their primary endpoints in clinical efficacy studies,
      despite demonstrating the desired immunogenicity profile and efficacy in young
      rodent models. Here, one of the RSV F vaccine candidates (post-fusion
      conformation, RSV post-F), and a stabilized pre-fusion form of RSV F (RSV pre-F,
      DS-Cav1) were evaluated in aged BALB/c mice. Humoral and cellular immunogenicity
      elicited after immunization of naive, aged mice was generally lower compared to
      young animals. In aged mice, RSV post-F vaccination without adjuvant poorly
      protected the respiratory tract from virus replication, and addition of GLA-SE
      only improved protection in the lungs, but not in nasal turbinates. RSV pre-F
      induced higher neutralizing antibody titers compared to RSV post-F (as previously
      reported) but interestingly, RSV F-specific CD8 T cell responses were lower
      compared to RSV post-F responses regardless of age. The vaccines were also tested
      in RSV seropositive aged mice, in which both antigen forms similarly boosted
      neutralizing antibody titers, although GLA-SE addition boosted neutralizing
      activity only in RSV pre-F immunized animals. Cell-mediated immune responses in
      the aged mice were only slightly boosted and well below levels induced in
      seronegative young mice. Taken together, the findings suggest that the vaccine
      candidates were not able to induce a strong anti-RSV immune response in recipient
      mice with an aged immune system, in agreement with recent human clinical trial
      results. Therefore, the aged mouse model could be a useful tool to evaluate
      improved vaccine candidates, targeted to prevent RSV disease in older adults.

PMID- 29182684
TI  - Colorectal cancer stages transcriptome analysis.
AB  - Colorectal cancer (CRC) is the third most common cancer and the second leading
      cause of cancer-related deaths in the United States. The purpose of this study
      was to evaluate the gene expression differences in different stages of CRC. Gene
      expression data on 433 CRC patient samples were obtained from The Cancer Genome
      Atlas (TCGA). Gene expression differences were evaluated across CRC stages using
      linear regression. Genes with p<=0.001 in expression differences were evaluated
      further in principal component analysis and genes with p<=0.0001 were evaluated
      further in gene set enrichment analysis. A total of 377 patients with gene
      expression data in 20,532 genes were included in the final analysis. The numbers
      of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4
      gene, which encodes for NIMA related kinase 4, was differentially expressed
      across the four stages of CRC. The stage I patients had the highest expression of
      NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6).
      Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2,
      C20orf135 and SPSB3) had p value of 0.0001 in the differential expression
      analysis. Principal component analysis indicated that the patients from the 4
      clinical stages do not appear to have distinct gene expression pattern. Network
      based and pathway-based gene set enrichment analyses showed that these 11 genes
      map to multiple pathways such as meiotic synapsis and packaging of telomere ends,
      etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome,
      DNA packaging complex and protein-DNA interactions. The protein complex-based
      gene set analysis showed that four genes were involved in H2AX complex II. This
      study identified a small number of genes that might be associated with clinical
      stages of CRC. Our analysis was not able to find a molecular basis for the
      current clinical staging for CRC based on the gene expression patterns.

PMID- 29182686
TI  - Vertical organization of the division of labor within nests of the Florida
      harvester ant, Pogonomyrmex badius.
AB  - In the Florida harvester ant, Pogonomyrmex badius, foragers occur only in the top
      15 cm of the nest, whereas brood and brood-care workers reside mostly in the
      deepest regions, yet the food and seeds foragers collect must be transported
      downward 30 to 80 cm to seed chambers and up to 2 m to brood chambers. Using mark
      recapture techniques with fluorescent printer's ink, we identified a class of
      workers that ranges widely within the vertical structure of the nest, rapidly
      moving materials dropped by foragers in the upper regions downward, and excavated
      soil from deeper upward. Within the nest, only 5% of foragers were recovered
      below 20 cm depth, but about 30% of transfer workers and 82% of unmarked workers
      were found there. Below 70 cm depth, 90% of workers were unmarked, and were
      probably involved mostly in brood care. During the summer, the transfer workers
      comprise about a quarter of the nest population, while foragers make up about
      40%. Workers marked as transfer workers later appear as foragers, while those
      marked as foragers die and disappear from the foraging population, suggesting
      that transfer workers are younger, and age into foraging. The importance of these
      findings for laboratory studies of division of labor are discussed. The efficient
      allocation of labor is a key component of superorganismal fitness.

PMID- 29182685
TI  - miR205 inhibits stem cell renewal in SUM159PT breast cancer cells.
AB  - miR205 has a dual activity, as tumor suppressor and as oncogene. Here we analyzed
      the impact of miR205 ectopic expression in the initial tumorigenic processes of
      SUM159PT, a triple negative breast cancer cell line with low endogenous levels of
      miR205. In SUM159PT, miR205 inhibited expression of its targets VEGFA, ErbB3,
      Zeb1, Fyn and Lyn A/B; it reduced cell proliferation, and Myc/cyclin D1 levels,
      while increased p27kip1 expression. miR205 abolished anchorage-independent
      growth, inhibited migration and invasion, Src-kinases/Stat3 axis activation, and
      levels of secreted MMP9. miR205 also reduced expression of CD44 and TAZ, E2A.E12,
      Twist, Snail1 and CK5, associated with epithelial-mesenchymal transition (EMT).
      Importantly, we show that miR205 inhibited SUM159PT cancer-stem cell renewal,
      expression in mammospheres of CD44 and ALDH1 stem-cell markers, TAZ, and E2A.E12.
      All these effects of miR205 were reverted by Anti-miR205 co-expression,
      demonstrating its specificity. Thus, all these results strongly suggest that
      ectopic expression of miR205 in SUM159PT affected several parameters associated
      with initial steps of tumorigenesis.

PMID- 29182687
TI  - Semi-automatic tracking, smoothing and segmentation of hyoid bone motion from
      videofluoroscopic swallowing study.
AB  - Motion analysis of the hyoid bone via videofluoroscopic study has been used in
      clinical research, but the classical manual tracking method is generally labor
      intensive and time consuming. Although some automatic tracking methods have been
      developed, masked points could not be tracked and smoothing and segmentation,
      which are necessary for functional motion analysis prior to registration, were
      not provided by the previous software. We developed software to track the hyoid
      bone motion semi-automatically. It works even in the situation where the hyoid
      bone is masked by the mandible and has been validated in dysphagia patients with
      stroke. In addition, we added the function of semi-automatic smoothing and
      segmentation. A total of 30 patients' data were used to develop the software, and
      data collected from 17 patients were used for validation, of which the
      trajectories of 8 patients were partly masked. Pearson correlation coefficients
      between the manual and automatic tracking are high and statistically significant
      (0.942 to 0.991, P-value<0.0001). Relative errors between automatic tracking and
      manual tracking in terms of the x-axis, y-axis and 2D range of hyoid bone
      excursion range from 3.3% to 9.2%. We also developed an automatic method to
      segment each hyoid bone trajectory into four phases (elevation phase, anterior
      movement phase, descending phase and returning phase). The semi-automatic hyoid
      bone tracking from VFSS data by our software is valid compared to the
      conventional manual tracking method. In addition, the ability of automatic
      indication to switch the automatic mode to manual mode in extreme cases and
      calibration without attaching the radiopaque object is convenient and useful for
      users. Semi-automatic smoothing and segmentation provide further information for
      functional motion analysis which is beneficial to further statistical analysis
      such as functional classification and prognostication for dysphagia. Therefore,
      this software could provide the researchers in the field of dysphagia with a
      convenient, useful, and all-in-one platform for analyzing the hyoid bone motion.
      Further development of our method to track the other swallowing related
      structures or objects such as epiglottis and bolus and to carry out the 2D curve
      registration may be needed for a more comprehensive functional data analysis for
      dysphagia with big data.

PMID- 29182689
TI  - A novel strategy to construct Janus metallamacrocycles with both a Ru-arene face
      and an imidazolium face.
AB  - The bottom-up construction of highly functional metallamacrocycles from simple
      building blocks is a challenge of much current interest. We have used
      solvothermal reactions of a bifunctional p-bitmb ligand with [Ru(arene)X2]2 in
      CH2Cl2 or CH2Br2 to generate the novel mononuclear metallamacrocyclic
      [RuX(arene)L2CH2]X3 complexes 1-3 (1, arene = p-cym, X = Cl; 2, arene = bip, X =
      Cl; 3, arene = p-cym, X = Br), which were characterized by various techniques.
      These complexes are "bowl-like" and have two faces: one coordinative Ru centre
      (arene)Ru(N,N)X bridged by L (L = 1,4-bis(imidazol-1-ylmethyl)-2,3,5,6
      tetramethylbenzene, p-bitmb) to a dipositive bis-imidazolinium centre. Cl- or Br-
      anions can be trapped inside the cavity of the "bowl-like" structure, forming H
      bonds with the backbone. Experimental (NMR and ESI-MS) and computational (DFT
      calculations) studies show that the source of the bridging -CH2- group is the
      dihalogenated solvent (CH2Cl2 or CH2Br2) that links the two arms of an initially
      formed non-cyclic complex (arene)RuX2L2 by a mechanism of nucleophilic
      substitution. Optimization of the reaction conditions afforded the macrocyclic
      complexes in almost quantitative yields. The applications of these complexes as
      anti-proliferative agents towards cancer cells and for selective anion sensing
      have been explored.

PMID- 29182690
TI  - Improving the mass transport of copper-complex redox mediators in dye-sensitized
      solar cells by reducing the inter-electrode distance.
AB  - In this work, we study the influence of the distance between electrodes on the
      performance of dye-sensitized solar cells based on TiO2 using the organic dye
      LEG4 and a Cu(dmp)2 redox couple (dmp = dimethyl phenantroline). The solar cells
      are characterized by a large open circuit voltage of up to 1.03 V, and an
      efficiency of 8.2% has been achieved for a 5.3 MUm thick TiO2 film using an epoxy
      resin-based sealed cell configuration with a minimal separation between
      electrodes. Transient short-circuit photocurrent measurements up to an intensity
      of 3 Suns show a significant decay in photocurrent after an initial peak current
      upon switching on the light for larger distance, resulting in a lower steady
      state photocurrent. For the smaller distance cells, the steady state photocurrent
      is linear with light intensity up to 2 Suns. Charge extraction measurements under
      short-circuit conditions show that reducing the distance between electrodes
      increases the electron collection efficiency and thus, the attainable
      photocurrent. Recombination losses increase with larger electrode separation
      distance and higher light intensity due to mass transport limitation of the redox
      mediator. Electrochemical impedance measurements confirm the effect of electrode
      distance on the redox couple transport, showing an additional loop with
      increasing distance. For the configuration where the TiO2 film is in very close
      proximity to the PEDOT-covered counter electrode, inductive behavior is observed
      at low frequencies. The inductive behavior disappears with the incorporation of
      an insulating porous ZrO2 layer. The equivalent circuit for the solar cell has
      been expanded to include this effect.

PMID- 29182691
TI  - Huge enhancement of upconversion luminescence by dye/Nd3+ sensitization of
      quenching-shield sandwich structured upconversion nanocrystals under 808 nm
      excitation.
AB  - Lanthanide-doped upconversion nanoparticles (UCNPs) have shown potential
      applications in diverse fields. However, their upconversion luminescence (UCL)
      intensity and excitation wavelength range are limited by the weak and narrowband
      absorption of lanthanide ions. Herein, we introduce and validate a strategy to
      largely increase the absorptivity and upconversion luminescence intensity under
      808 nm excitation by broadband dye-sensitized quenching-shield sandwich
      structured upconversion nanocrystals NaLuF4:Gd,Yb,Tm@NaLuF4:Gd,Yb@NaNdF4:Yb. The
      dye molecules anchored on the surface of the UCNPs serve as an antenna which can
      broadly and strongly harvest NIR light. The Nd3+ facilitates the energy transfer
      and photon upconversion of the lanthanide activator at a biocompatible excitation
      wavelength (around 800 nm) with a significant increase in penetration ability and
      minimizes the overheating problem associated with conventional 980 nm excitation.
      The quenching-shield sandwich structure can greatly eliminate the deleterious
      cross-relaxation pathway between the activator and sensitizer. This approach
      combines the merits of the use of Nd3+ as a sensitizer, a quenching-shield
      sandwich structure and the "antenna" effect, leading to a tremendous enhancement
      of UCL under excitation at 808 nm. These well-designed UCNPs excited at 808 nm
      with improved optical performances will outperform conventional UCNPs excited at
      980 nm and play an important role in the development of luminescent probes for
      future biological and medical applications.

PMID- 29182692
TI  - Novel chloride-centered Ag18 clusters featuring a cuboctahedral Ag12 skeleton.
AB  - Two novel chloride-centered Ag18 clusters with the same framework but different
      supporting phosphines are synthesized by the reaction of PhC[triple bond, length
      as m-dash]CAg, AgSbF6, PPh3 (or P(p-Tol)3), and NaBH4 in CH2Cl2, followed by the
      addition of PhC[triple bond, length as m-dash]CH and NEt3. The inner twelve Ag
      atoms of these two clusters are arranged in a rare cuboctahedral structure, which
      can be rationalized by considering a ligand effect. Through careful analysis, we
      find that the central chloride arises from a generally ignored but nonetheless
      existing reaction between CH2Cl2 and NEt3, which is well recognized as the
      Menshutkin reaction. This research provides insights into the dependence of the
      cluster structure on the nature of the ligand and into the cluster formation
      mechanism of the Menshutkin reaction.

PMID- 29182693
TI  - H2O2 induced formation of graded composition sodium-doped tin dioxide and
      template-free synthesis of yolk-shell SnO2 particles and their sensing
      application.
AB  - Sodium peroxostannate nanoparticles with graded composition were produced from
      aqueous hydrogen peroxide-sodium hydroxostannate solution. The uniform particles
      were converted to composition graded sodium stannate by mild thermal treatment
      for peroxide decomposition and yielded yolk-shell tin dioxide particles by dilute
      acid treatment. The mechanism of formation of the graded sodium concentration is
      explained in view of the solubility of peroxostannate in H2O2-H2O solution and
      based on 119Sn NMR, XRD, dynamic light scattering (DLS) and electron microscopy
      studies. Initial studies illuminating sensitive hydrogen sensing by yolk-shell
      tin oxide particles are presented.

PMID- 29182688
TI  - Interferon-gamma release assay for the diagnosis of latent tuberculosis
      infection: A latent-class analysis.
AB  - BACKGROUND: Accurate diagnosis and subsequent treatment of latent tuberculosis
      infection (LTBI) is essential for TB elimination. However, the absence of a gold
      standard test for diagnosing LTBI makes assessment of the true prevalence of LTBI
      and the accuracy of diagnostic tests challenging. Bayesian latent class models
      can be used to make inferences about disease prevalence and the sensitivity and
      specificity of diagnostic tests using data on the concordance between tests. We
      performed the largest meta-analysis to date aiming to evaluate the performance of
      tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) for LTBI
      diagnosis in various patient populations using Bayesian latent class modelling.
      METHODS: Systematic search of PubMeb, Embase and African Index Medicus was
      conducted without date and language restrictions on September 11, 2017 to
      identify studies that compared the performance of TST and IGRAs for LTBI
      diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT
      GIT) and T-SPOT.TB. Studies were included if they reported 2x2 agreement data
      between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed
      to estimate the sensitivity and specificity of TST and IGRAs in various
      populations, including immune-competent adults, immune-compromised adults and
      children. A TST cut-off value of 10 mm was used for immune-competent subjects and
      5 mm for immune-compromised individuals. FINDINGS: A total of 157 studies were
      included in the analysis. In immune-competent adults, the sensitivity of TST and
      QFT-GIT were estimated to be 84% (95% credible interval [CrI] 82-85%) and 52% (50
      53%), respectively. The specificity of QFT-GIT was 97% (96-97%) in non-BCG
      vaccinated and 93% (92-94%) in BCG-vaccinated immune-competent adults. The
      estimated figures for TST were 100% (99-100%) and 79% (76-82%), respectively. T
      SPOT.TB has comparable specificity (97% for both tests) and better sensitivity
      (68% versus 52%) than QFT-GIT in immune-competent adults. In immune-compromised
      adults, both TST and QFT-GIT display low sensitivity but high specificity. QFT
      GIT and TST are equally specific (98% for both tests) in non-BCG-vaccinated
      children; however, QFT-GIT is more specific than TST (98% versus 82%) in BCG
      vaccinated group. TST is more sensitive than QFT-GIT (82% versus 73%) in
      children. CONCLUSIONS: This study is the first to assess the utility of TST and
      IGRAs for LTBI diagnosis in different population groups using all available data
      with Bayesian latent class modelling. Our results challenge the current beliefs
      about the performance of LTBI screening tests, and have important implications
      for LTBI screening policy and practice. We estimated that the performance of
      IGRAs is not as reliable as previously measured in the general population.
      However, IGRAs are not or minimally affected by BCG and should be the preferred
      tests in this setting. Adoption of IGRAs in settings where BCG is widely
      administered will allow for a more accurate identification and treatment of LTBI.

PMID- 29182696
TI  - The effect of the functional ionic group of the viologen derivative on visible
      light driven CO2 reduction to formic acid with the system consisting of water
      soluble zinc porphyrin and formate dehydrogenase.
AB  - The effect of the functional ionic group of 4,4'-bipyridinium salt derivatives
      (4,4'-BPs) as the electron carrier on the visible-light driven conversion of CO2
      to formic acid with the system consisting of water-soluble zinc
      tetraphenylporphyrin tetrasulfonate (ZnTPPS) and formate dehydrogenase (FDH) in
      the presence of triethanolamine (TEOA) as an electron donor was investigated.
      1,1'-Diaminoethyl- (DAV), 1-aminoethyl-1'-methyl- (AMV), 1-carboxymethyl-1'
      methyl- (CMV) and 1,1'-dicarboxymethyl-4,4'-bipyridinium salt (DCV) were prepared
      as the 4,4'-BPs with the functional ionic group. Irradiation of a CO2 saturated
      buffer solution containing TEOA, ZnTPPS, 4,4'-BP and FDH with visible light
      irradiation resulted in the production of formic acid. By using 4,4'-BPs with the
      cationic aminoethyl-group, DAV or AMV as an electron carrier, the effective
      visible-light driven formic acid production based on the CO2 reduction was
      observed compared to the 4,4'-BPs with the anionic carboxymethyl-group, CMV or
      DCV. The formic acid production rate with DAV was approximately 3.2 times higher
      than that of the system with DCV.

PMID- 29182698
TI  - Optical limiters with improved performance based on nanoconjugates of thiol
      substituted phthalocyanine with CdSe quantum dots and Ag nanoparticles.
AB  - Two alternative synthetic approaches affording a low-symmetry A3B-type
      phthalocyanine 1 bearing two [2'-(2''-mercaptoethoxy)ethoxy] anchoring
      substituents were developed. Due to the presence of thiol groups, this
      phthalocyanine could be conjugated with TOPO-capped (TOPO - trioctylphosphine)
      capped CdSe quantum dots (CdSe-QDs) or oleylamine capped silver nanoparticles (Ag
      NPs). The nonlinear optical behaviour of starting phthalocyanine, quantum dots,
      nanoparticles and their conjugates was studied by using an open aperture Z-scan
      technique, revealing that the grafting of 1 onto the nanomaterials resulted in a
      significant enhancement of the optical limiting of 1-Ag and 1-CdSe in comparison
      with the individual components. The conjugate 1-CdSe, being the first example of
      Pc-based thiol conjugated with quantum dots, revealed superior limiting
      characteristics with a limiting threshold below 0.18 J cm-2.

PMID- 29182699
TI  - Is the largest aqueous gold cluster a superatom complex? Electronic structure &
      optical response of the structurally determined Au146(p-MBA)57.
AB  - The new water-soluble gold cluster Au146(p-MBA)57, the structure of which has
      been recently determined at sub-atomic resolution by Vergara et al., is the
      largest aqueous gold cluster ever structurally determined and likewise the
      smallest cluster with a stacking fault. The core presents a twinned truncated
      octahedron, while additional peripheral gold atoms follow a C2 rotational
      symmetry. According to the usual counting rules of the superatom complex (SAC)
      model, the compound attains a number of 92 SAC electrons if the overall net
      charge is 3- (three additional electrons). As this is the number of electrons
      required for a major shell closing, the question arises of whether Au146(p-MBA)57
      should be regarded as a superatom complex. Starting from the experimental
      coordinates we have analyzed the structure using density-functional theory. The
      optimized (relaxed) structure retains all the connectivity of the experimental
      coordinates, while removing much of its irregularities in interatomic distances,
      thereby enhancing the C2-symmetry feature. On analyzing the angular-momentum
      projected states, we show that, despite a small gap, the electronic structure
      does not exhibit SAC model character. In addition, optical absorption spectra are
      found to be relatively smooth compared to the example of the Au144(SR)60 cluster.
      The Au146(SR)57 does not derive its stability from SAC character; it cannot be
      considered as a superatom complex.

PMID- 29182702
TI  - Swings and Roundabouts in CNS Drug Biomarkers.

PMID- 29182703
TI  - Clinical Effects of Oral Tramiprosate in APOE4/4 Homozygous Patients with Mild
      Alzheimer's Disease Suggest Disease Modification.

PMID- 29182704
TI  - Dementia Prevention by Disease-Modification through Nutrition.

PMID- 29182705
TI  - Potential Utility of Practice Effects in Preventive Trials.

PMID- 29182706
TI  - Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild
      Alzheimer's Disease Suggest Disease Modification Potential.
AB  - BACKGROUND: Alzheimer's Disease (AD) patients homozygous for the APOE4 allele
      (APOE4/4) have a distinct clinical and biological phenotype with high levels of
      beta amyloid (Abeta) pathology and toxic Abeta oligomers. Tramiprosate, an oral
      agent that inhibits Abeta monomer aggregation into toxic oligomers, was evaluated
      in two Phase 3 Mild to Moderate AD studies which did not show efficacy in the
      overall population. Re-analyses of these trials showed the most consistent
      clinical benefits in APOE4/4 patients. We analyzed efficacy in the APOE4/4
      patients with Mild disease. OBJECTIVES: To determine the optimal stage of AD for
      future trials in APOE4/4 homozygotes. DESIGN: Two randomized, double-blind,
      placebo-controlled parallel-arm multi-center studies of 78-weeks duration.
      SETTING: Academic Alzheimer's disease centers, community-based memory clinics,
      and neuropsychiatric research sites. PARTICIPANTS: Participants included 2,025 AD
      patients with MMSE 16-26. Approximately 13-15% had APOE4/4 genotype (N= 147 and
      110 per study), mean age 71.1 years, 56% females. Almost all were on stable
      symptomatic drugs. INTERVENTION: Randomized subjects received oral placebo, 100mg
      BID, or 150mg BID of tramiprosate. MEASUREMENTS: Co-primary outcomes were change
      from baseline in the ADAS-cog11 and CDR-SB. Disability assessment for dementia
      (DAD) was a secondary outcome. RESULTS: In APOE4/4 homozygotes receiving 150mg
      BID tramiprosate, efficacy in the traditional Mild AD patients (MMSE 20-26) was
      higher than the overall group (MMSE 16-26) and efficacy in the Mild patients
      (MMSE 22-26) was highest. Tramiprosate benefits compared to placebo on ADAS-cog,
      CDR-SB, and DAD were 125%, 81% and 71%, respectively (p<0.02). The Mild subgroup
      (MMSE 22-26) showed cognitive stabilization with no decline over 78 weeks, both
      ADAS-cog and DAD effects increased over time. Tramiprosate safety in APOE4/4
      patients was favorable. Most common adverse events were nausea, vomiting,
      depression and decreased weight. CONCLUSIONS: The Mild subgroup of APOE4/4 AD
      patients (MMSE 22-26) showed larger benefits on the high dose of tramiprosate
      than the overall Mild and Moderate group. Consistent with its preclinical effects
      on Abeta oligomers, tramiprosate seemed to stabilize cognitive performance,
      supporting its disease modification potential. Confirmatory studies using ALZ
      801, an improved pro-drug formulation of tramiprosate, will target APOE4/4
      patients with Mild AD.

PMID- 29182709
TI  - The ROSAS Cohort: A Prospective, Longitudinal Study of Biomarkers for Alzheimer's
      Disease. Strategy, Methods and Initial Results.
AB  - OBJECTIVE: The aims of the Research Of biomarkers in Alzheimer's diseaSe (ROSAS)
      study were to determine the biofluid and imaging biomarkers permitting an early
      diagnosis of Alzheimer's disease and better characterisation of cognitive and
      behavioural course of the pathology. This paper outlines the overall strategy,
      methodology of the study, baseline characteristics of the population and first
      longitudinal results from the ROSAS cohort. METHODS: Longitudinal prospective
      monocentric observational study performed at the Alzheimer's disease Research
      centre in Toulouse. A total of 387 patients were studied and analyzed in 3
      groups: 184 patients with dementia of Alzheimer's type, 96 patients with memory
      disorders without dementia (Mild Cognitive Impairment) and 107 patients without
      abnormal memory tests (control group), and were followed up during 4 years.
      Patient's sociodemographic characteristics, risk factors, medical conditions,
      previous and current medications, neuropsychological assessment and overall
      cognitive status were recorded. Blood and urine samples were collected at every
      year, Magnetic Resonance Imaging were performed at inclusion, after one year of
      follow-up and at the end of the study. RESULTS: At baseline, three different
      groups of the cohort differed interestingly in age, level of education, and in
      percentage of ApoEepsilon4 carriers whereas the history of cardiovascular and
      endocrine pathologies were similar among the groups. During the follow-up period
      (3-4 years) 42 mild cognitive impairment patients (43.8%) progressed to dementia,
      7 controls progressed into mild cognitive impairment and 1 patient in the control
      group converted from mild cognitive impairment group to dementia of Alzheimer's
      type group. During the first year of follow up, the incidence of progression from
      mild cognitive impairment to dementia of Alzheimer's type was 12.7 per 100,
      during the second year 33.9 per 100 and 46.7 per 100 for the third year.
      CONCLUSION: This paper presents the baseline characteristics of the unique French
      prospective monocenter study in which the natural course of dementia of
      Alzheimer's type was evaluated. Future analysis of blood and urine samples
      collection from the ROSAS study will permit to identify possible biofluid
      biomarkers predicting the early stages of the dementia of Alzheimer's type and
      risk of progression from Mild Cognitive Impairment to Alzheimer's disease.

PMID- 29182707
TI  - Sex and Age Differences in the Association of Blood Pressure and Hypertension
      with Cognitive Function in the Elderly: The Rancho Bernardo Study.
AB  - OBJECTIVES: This study examines sex and age differences in associations of
      systolic and diastolic blood pressure (SBP, DBP), pulse pressure and hypertension
      with cognitive function in a community-dwelling population. DESIGN: Cross
      sectional study. SETTING: Research clinic visit in 1988-91. PARTICIPANTS:
      Participants were 693 men and 1022 women aged 50-97 Measurements: Blood pressure
      was measured and 12 cognitive function tests were administered. RESULTS: Average
      age was 73.8+/-9.9 in men and 73.2+/-9.3 in women; 62.6% of men and 63.4% of
      women were hypertensive (SBP>=140 mmHg, DBP>=90 mmHg, or antihypertensive
      medication use). Each 5-unit increment in SBP, DBP, or pulse pressure and
      categorical hypertension was associated with significantly increased odds of poor
      verbal fluency performance in men and poor Trails B performance in women, with
      strongest associations for hypertension (OR=1.97, CI:1.01,3.85 in men; OR=1.51,
      CI:1.01,2.26 in women). After age stratification, associations remained
      statistically significant in younger (<80 years ) but not older (>=80 years)
      participants. CONCLUSION: Blood pressure as a continuous or categorical variable
      was associated with poor performance on cognitive function tests, but domains
      varied by sex and associations were found only in those younger than 80 years.
      The absent associations in those aged 80 years and older could support the
      hypothesis that increased blood flow is required to maintain cerebral perfusion
      with advancing age, or could reflect a survivor effect.

PMID- 29182710
TI  - Objective Cognitive Impairment and Progression to Dementia in Women: The
      Prospective Epidemiological Risk Factor Study.
AB  - BACKGROUND: Identification of subjects with a progressive disease phenotype is an
      urgent need in the pharmaceutical industry where most of the recent clinical
      trials in Alzheimer's disease have failed. OBJECTIVES: The objective of this
      study was to identify subgroups of individuals with objective cognitive
      impairment (OCI), who were most likely to progress to dementia and to identify
      the risk factors associated with progression. DESIGN: Prospective cohort study.
      SETTING: Population-based. PARTICIPANTS: 5,380 elderly women from Denmark.
      MEASUREMENTS: The Short Blessed Test and a category fluency test with animal
      naming, was used to assess cognitive function, and to classify them into
      different groups of OCI. RESULTS: OCI was identified in 852 subjects at baseline.
      The risk of dementia was elevated for OCI subjects as compared to subjects with
      normal cognition (HR 1.46[1.19-1.79]). The courses of OCI were studied in a sub
      cohort who completed the cognitive assessment at both the baseline and the follow
      up visit (n = 1,933). Of these subjects 203 had OCI at baseline. The multi-domain
      subtypes of OCI were associated with progressive OCI. Subjects most likely to
      progress were older, physically inactive, had a higher level of total cholesterol
      (>6.5 mmol/L) and had a history of depression as compared to subjects with a non
      progressive course of OCI. CONCLUSIONS: In this cohort we identified a risk
      profile associated with progression from OCI in older women. The degree of
      impairment at baseline was an important predictor of conversion to dementia,
      additionally several modifiable risk factors were associated with progression.

PMID- 29182708
TI  - B-Vitamin Therapy for Kidney Transplant Recipients Lowers Homocysteine and
      Improves Selective Cognitive Outcomes in the Randomized FAVORIT Ancillary
      Cognitive Trial.
AB  - BACKGROUND: Objectives: Elevated plasma total homocysteine (tHcy) is associated
      with increased risk of cardiovascular disease, stroke and dementia. Results of
      clinical trials using B-vitamins to reduce the cognitive risks attributed to tHcy
      have been inconsistent. The high prevalence of both hyperhomocysteinemia and
      cognitive impairment among kidney transplant recipients makes them an important
      population in which to evaluate the effect of lowering homocysteine on cognitive
      function. We therefore evaluated whether B-vitamin therapy to lower tHcy would
      prevent cognitive-decline in a cohort of stable kidney transplant recipients.
      DESIGN: The study was a longitudinal ancillary of the FAVORIT trial, a
      randomized, placebo-controlled multi-site trial of high-dose B vitamins to reduce
      cardiovascular and cerebrovascular events in clinically stable kidney transplant
      recipients with elevated tHcy. PARTICIPANTS: 584 participants from 18 sites
      across North America. INTERVENTION: The intervention consisted of a daily
      multivitamin containing high-doses of folate (5.0 mg), vitamin B12 (1.0 mg) and
      vitamin B6 (50 mg). The placebo consisted of a daily multi-vitamin containing no
      folate and recommended daily allowances of vitamins B12 and B6 (0 mg folate; 2.0
      ug vitamin B12; 1.4 mg vitamin B6). MEASUREMENTS: Annual neuropsychological
      assessment for up to 5 years (mean 3.3 years) using a standardized test battery.
      Efficacy was analyzed on an intention-to-treat basis using end-of-trial data.
      Subgroup analyses included stratification for baseline plasma B-vitamin and tHcy
      concentrations. RESULTS: At baseline, cognitive impairment was common with 61% of
      participants falling more than one standard deviation below published norms for
      at least one cognitive test. Fewer than 1% of participants had insufficient
      plasma folate < 5 ng/ml or vitamin B12 < 148 pmol/L. However, 44.6% had plasma B6
      concentrations < 30 nmol/L. At follow-up, processing speed and memory scores were
      modestly but significantly better in the B-vitamin supplement group than in
      controls (p<=0.05). There was no interaction between baseline tHcy, B-vitamin
      status and treatment on the cognitive outcomes. CONCLUSIONS: High-dose B-vitamin
      supplementation provided modest cognitive benefit for kidney transplant
      recipients with elevated baseline tHcy. Since nearly all participants were folate
      and vitamin B12 sufficient at baseline, the potential cognitive benefits of
      folate and B12 supplementation in individuals with poor B-vitamin status remains
      to be determined.

PMID- 29182711
TI  - Evaluation of the Neuroprotective Potential of N-Acetylcysteine for Prevention
      and Treatment of Cognitive Aging and Dementia.
AB  - Alzheimer's disease is a progressive neurodegenerative disease for which there is
      no cure and only a few treatments providing little relief. Increased oxidative
      stress that is associated with aging is strongly implicated in the pathogenesis
      and progression of Alzheimer's disease. Studies have shown that levels of the
      endogenous antioxidant glutathione decline at an early stage of Alzheimer's
      disease with decreased levels correlating with worse cognitive functions. N
      acetylcysteine, a drug also widely available as a dietary supplement, is a
      precursor of L-cysteine, which in turn is a component of glutathione. Because
      cysteine availability is a limiting factor for glutathione synthesis, treatment
      with N-acetylcysteine may increase glutathione levels and thereby counter
      oxidative stress, promote redox -regulated cell signaling, and improve immune
      responses. In this review, we evaluate the existing literature and the potential
      of N-acetylcysteine in promoting cognitive health and alleviating cognitive
      decline associated with dementia. Discussion will also include possible
      mechanisms of action of N-acetylcysteine, its effects on aging biology, and
      safety of long-term use. Based on the available literature, a nutraceutical
      formulation containing N-acetylcysteine among other compounds has shown some pro
      cognitive benefits in Alzheimer's patients and older adults, but the evidence for
      N-acetylcysteine alone is less robust. Although N-acetylcysteine crosses the
      blood-brain-barrier, low bioavailability is an obstacle. One promising avenue of
      research may be to explore derivatives of N-acetylcysteine such as N
      acetylcysteine amide, which has been reported in preclinical studies to have
      higher permeability through cellular and mitochondrial membranes with increased
      central nervous system bioavailability compared to N-acetylcysteine.

PMID- 29182712
TI  - Sarcopenia Is Negatively Related to High Gravitational Impacts Achieved From Day
      to-day Physical Activity.
AB  - Background: Sarcopenia has been associated with reduced physical activity (PA).
      We aimed to determine if sarcopenia, and specific components of muscle size,
      function, and physical performance, are associated with high impacts achieved
      during habitual PA, as these are related to bone strength in community-dwelling
      older women. Methods: Participants were older women from the Cohort of Skeletal
      Health in Bristol and Avon. We defined sarcopenia using the EWGSOP criteria.
      Lower limb peak muscle power and force were assessed using Jumping Mechanography
      (JM). High vertical impacts were assessed by tri-axial accelerometry (at least
      1.5g above gravity). Cross-sectional associations were analyzed by linear
      regression, adjusting for age, height and weight (or fat mass for models
      including appendicular lean mass index), comorbidities, smoking, alcohol, and
      Index of Multiple Deprivation. Results: Our analyses included 380 participants,
      with mean age 76.7 (SD 3.0) years; 242 (64%) also completed JM. In age-adjusted
      analysis, a negative relationship was observed between severity of sarcopenia and
      high, but not medium or low, impacts (p = .03 for trend). Regarding components of
      sarcopenia underlying this relationship, multivariable analyses revealed that
      gait speed (beta 1.47 [95% CI 1.14, 1.89], [beta-1] reflects the proportionate
      increase in high impacts per SD increase in exposure) and peak force (1.40 [1.07,
      1.84]) were independently associated with high impacts. Conclusions: Older women
      with sarcopenia experienced fewer bone-strengthening high impacts than those with
      presarcopenia or without sarcopenia. To increase bone strengthening activity in
      older women, interventions need to improve both lower limb muscle force and
      walking speed.

PMID- 29182713
TI  - The direct effects of plant polyploidy on the legume-rhizobia mutualism.
AB  - Background: Polyploidy is known to significantly alter plant genomes, phenotypes
      and interactions with the abiotic environment, yet the impacts of polyploidy on
      plant-biotic interactions are less well known. A particularly important plant
      biotic interaction is the legume-rhizobia mutualism, in which rhizobia fix
      atmospheric nitrogen in exchange for carbon provided by legume hosts. This
      mutualism regulates nutrient cycles in natural ecosystems and provides nitrogen
      to agricultural environments. Despite the ecological, evolutionary and
      agricultural importance of plant polyploidy and the legume-rhizobia mutualism, it
      is not yet fully understood whether plant polyploidy directly alters mutualism
      traits or the consequences on plant growth. Scope: The aim was to propose a
      conceptual framework to understand how polyploidy might directly enhance the
      quantity and quality of rhizobial symbionts hosted by legume plants, resulting in
      increased host access to fixed nitrogen (N). Mechanistic hypotheses have been
      devised to examine how polyploidy can directly alter traits that impact the
      quantity (e.g. nodule number, nodule size, terminal bacteroid differentiation)
      and quality of symbionts (e.g. nodule environment, partner choice, host
      sanctions). To evaluate these hypotheses, an exhaustive review of studies testing
      the effects of plant polyploidy on the mutualism was conducted. In doing so,
      overall trends were synthesized, highlighting the limited understanding of the
      mechanisms that underlie variation in results achieved thus far, revealing
      striking gaps in knowledge and uncovering areas ripe for future research.
      Conclusions: Plant polyploidy can immediately alter nodule size, N fixation rate
      and the identity of rhizobial symbionts hosted by polyploid legumes, but many of
      the mechanistic hypotheses proposed here, such as bacteroid number and
      enhancements of the nodule environment, remain unexplored. Although current
      evidence supports a role of plant polyploidy in enhancing key aspects of the
      legume-rhizobia mutualism, the underlying mechanisms and effects on host benefit
      from the mutualism remain unresolved.

PMID- 29182714
TI  - Two critical brain networks for generation and combination of remote
      associations.
AB  - Recent functional imaging findings in humans indicate that creativity relies on
      spontaneous and controlled processes, possibly supported by the default mode and
      the fronto-parietal control networks, respectively. Here, we examined the ability
      to generate and combine remote semantic associations, in relation to creative
      abilities, in patients with focal frontal lesions. Voxel-based lesion-deficit
      mapping, disconnection-deficit mapping and network-based lesion-deficit
      approaches revealed critical prefrontal nodes and connections for distinct
      mechanisms related to creative cognition. Damage to the right medial prefrontal
      region, or its potential disrupting effect on the default mode network, affected
      the ability to generate remote ideas, likely by altering the organization of
      semantic associations. Damage to the left rostrolateral prefrontal region and its
      connections, or its potential disrupting effect on the left fronto-parietal
      control network, spared the ability to generate remote ideas but impaired the
      ability to appropriately combine remote ideas. Hence, the current findings
      suggest that damage to specific nodes within the default mode and fronto-parietal
      control networks led to a critical loss of verbal creative abilities by altering
      distinct cognitive mechanisms.

PMID- 29182715
TI  - Modulation of Rat 50-kHz Ultrasonic Vocalizations by Glucocorticoid Signaling:
      Possible Relevance to Reward and Motivation.
AB  - Background: Rats emit 50-kHz ultrasonic vocalizations (USVs) to communicate
      positive emotional states, and these USVs are increasingly being investigated in
      preclinical studies on reward and motivation. Although it is the activation of
      dopamine receptors that initiates the emission of 50-kHz USVs, non-dopaminergic
      mechanisms may modulate calling in the 50 kHz frequency band. To further
      elucidate these mechanisms, the present study investigated whether the
      pharmacological manipulation of glucocorticoid signaling influenced calling.
      Methods: Rats were administered corticosterone (1-5 mg/kg, s.c.), the
      glucocorticoid receptor antagonist mifepristone (40 or 100 mg/kg, s.c.), or the
      corticosterone synthesis inhibitor metyrapone (50 or 100 mg/kg, i.p.). The
      effects of these drugs on calling initiation and on calling recorded during
      nonaggressive social contacts or after the administration of amphetamine (0.25 or
      1 mg/kg, i.p.) were then evaluated. Results: Corticosterone failed to initiate
      the emission of 50-kHz USVs and did not influence pro-social and amphetamine
      stimulated calling. Similarly, mifepristone and metyrapone did not initiate
      calling. However, metyrapone suppressed pro-social calling and calling stimulated
      by a moderate dose (1 mg/kg, i.p.) of amphetamine. Conversely, mifepristone
      attenuated calling stimulated by a low (0.25 mg/kg, i.p.), but not moderate (1
      mg/kg, i.p.), dose of amphetamine and had no influence on pro-social calling.
      Conclusions: The present results demonstrate that glucocorticoid signaling
      modulates calling in the 50 kHz frequency band only in certain conditions and
      suggest that mechanisms different from the inhibition of corticosterone synthesis
      may participate in the suppression of calling by metyrapone.

PMID- 29182716
TI  - Epidemic spread of Escherichia coli ST744 isolates carrying mcr-3 and blaCTX-M-55
      in cattle in France.

PMID- 29182717
TI  - Doxycycline in the management of sexually transmitted infections.
AB  - Doxycycline is a second-generation tetracycline, available worldwide for half a
      century. It is an inexpensive broad-spectrum antimicrobial agent largely used in
      the management of several bacterial infections, particularly involving
      intracellular pathogens, as well as in the treatment of acne or for the
      prophylaxis of malaria. Physicochemical characteristics of doxycycline
      (liposolubility) allow a high diffusion in the tissues and organs. It has high
      bioavailability and a long elimination half-life allowing oral administration of
      one or two daily doses. Over the last decade, the prevalence of bacterial
      sexually transmitted infections (STIs) (syphilis, chlamydiosis, gonorrhoea and
      Mycoplasma genitalium infections) has increased in most countries, mainly in MSM,
      many of whom are infected with HIV. In light of increasing prevalence of
      resistance towards first-line regimens of some STI agents and recently updated
      recommendations for STI management, doxycycline appears to be an attractive
      option compared with other available antibiotics for the treatment of some STIs
      due to its efficacy, good tolerability and oral administration. More recently,
      indications for doxycycline in STI prophylaxis have been evaluated. Considering
      the renewed interest of doxycycline in STI management, this review aims to update
      the pharmacology of, efficacy of, safety of and resistance to doxycycline in this
      context of use.

PMID- 29182718
TI  - A 3D Human Airway Model Enables Prediction of Respiratory Toxicity of Inhaled
      Drugs In Vitro.
AB  - Respiratory tract toxicity represents a significant cause of attrition of inhaled
      drug candidates targeting respiratory diseases. One of the key issues to allow
      early detection of respiratory toxicities is the lack of reliable and predictive
      in vitro systems. Here, the relevance and value of a physiologically relevant 3D
      human airway in vitro model (MucilAir) were explored by repeated administration
      of a set of compounds with (n = 8) or without (n = 7) respiratory toxicity
      following inhalation in vivo. Predictability for respiratory toxicity was
      evaluated by readout of cytotoxicity, barrier integrity, viability, morphology,
      ciliary beating frequency, mucociliary clearance and cytokine release.
      Interestingly, the data show that in vivo toxicity can be predicted in vitro by
      studying cell barrier integrity by transepithelial electrical resistance (TEER),
      and cell viability determined by the Resazurin method. Both read-outs had 88%
      sensitivity and 100% specificity, respectively, while the former was more
      accurate with receiver operating characteristic (ROC) AUC of 0.98 (p = .0018)
      compared with ROC AUC of 0.90 (p = .0092). The loss of cell barrier integrity
      could mainly, but not fully, be attributed to a loss of cell coverage in 6 out of
      7 compounds with reduced TEER. Notably, these effects occurred only at 400 uM, at
      concentration levels significantly above primary target cell potency, suggesting
      that greater attention to high local lung concentrations should be taken into
      account in safety assessment of inhaled drugs. Thus, prediction of respiratory
      toxicity in 3D human airway in vitro models may result in improved animal welfare
      and reduced attrition in inhaled drug discovery projects.

PMID- 29182719
TI  - Corrigendum to: Fear boosts the early neural coding of faces.

PMID- 29182720
TI  - Variation in xylem vulnerability to embolism in European beech from
      geographically marginal populations.
AB  - Climate change is expected to increase the frequency and intensity of droughts
      and heatwaves in Europe, leading to effects on forest growth and major forest
      dieback events due to hydraulic failure caused by xylem embolism. Inter-specific
      variability in embolism resistance has been studied in detail, but little is
      known about intra-specific variability, particularly in marginal populations. We
      evaluated 15 European beech populations, mostly from geographically marginal
      sites of the species distribution range, focusing particularly on populations
      from the dry southern margin. We found small, but significant differences in
      resistance to embolism between populations, with xylem pressures causing 50% loss
      of hydraulic conductivity ranging from -2.84 to -3.55 MPa. Significant phenotypic
      clines of increasing embolism resistance with increasing temperature and aridity
      were observed: the southernmost beech populations growing in a warmer drier
      climate and with lower habitat suitability have higher resistance to embolism
      than those from Northern Europe growing more favourable conditions. Previous
      studies have shown that there is little or no difference in embolism resistance
      between core populations, but our findings show that marginal populations have
      developed ways of protecting their xylem based on either evolution or plasticity.

PMID- 29182721
TI  - Molecular mimicry modulates plant host responses to pathogens.
AB  - Background: Pathogens often secrete molecules that mimic those present in the
      plant host. Recent studies indicate that some of these molecules mimic plant
      hormones required for development and immunity. Scope and Conclusion: This
      Viewpoint reviews the literature on microbial molecules produced by plant
      pathogens that functionally mimic molecules present in the plant host. This
      article includes examples from nematodes, bacteria and fungi with emphasis on
      RaxX, a microbial protein produced by the bacterial pathogen Xanthomonas oryzae
      pv. oryzae. RaxX mimics a plant peptide hormone, PSY (plant peptide containing
      sulphated tyrosine). The rice immune receptor XA21 detects sulphated RaxX but not
      the endogenous peptide PSY. Studies of the RaxX/XA21 system have provided insight
      into both host and pathogen biology and offered a framework for future work
      directed at understanding how XA21 and the PSY receptor(s) can be differentially
      activated by RaxX and endogenous PSY peptides.

PMID- 29182723
TI  - Extreme learning machines for reverse engineering of gene regulatory networks
      from expression time series.
AB  - Motivation: The reconstruction of gene regulatory networks (GRNs) from genes
      profiles has a growing interest in bioinformatics for understanding the complex
      regulatory mechanisms in cellular systems. GRNs explicitly represent the cause
      effect of regulation among a group of genes and its reconstruction is today a
      challenging computational problem. Several methods were proposed, but most of
      them require different input sources to provide an acceptable prediction. Thus,
      it is a great challenge to reconstruct a GRN only from temporal gene expression
      data. Results: Extreme Learning Machine (ELM) is a new supervised neural model
      that has gained interest in the last years because of its higher learning rate
      and better performance than existing supervised models in terms of predictive
      power. This work proposes a novel approach for GRNs reconstruction in which ELMs
      are used for modeling the relationships between gene expression time series.
      Artificial datasets generated with the well-known benchmark tool used in DREAM
      competitions were used. Real datasets were used for validation of this novel
      proposal with well-known GRNs underlying the time series. The impact of
      increasing the size of GRNs was analyzed in detail for the compared methods. The
      results obtained confirm the superiority of the ELM approach against very recent
      state-of-the-art methods in the same experimental conditions. Availability and
      implementation: The web demo can be found at http://sinc.unl.edu.ar/web-demo/elm
      grnnminer/. The source code is available at
      https://sourceforge.net/projects/sourcesinc/files/elm-grnnminer. Contact:
      mrubiolo@santafe-conicet.gov.ar. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29182722
TI  - Cryptic gene pools in the Hypericum perforatum-H. maculatum complex: diploid
      persistence versus trapped polyploid melting.
AB  - Background and Aims: In Central Europe Hypericum perforatum and Hypericum
      maculatum show significant hybridization and introgression as a consequence of
      Pleistocene range fluctuations, and their gene pools are merging on higher ploidy
      levels. This paper discusses whether polyploid hybrid gene pools are trapped in
      the ecological climatic niche space of their diploid ancestors, and tests the
      idea of geographical parthenogenesis. Methods: DNA sequence information of
      nuclear ribosomal DNA and plastid loci, ploidy level estimates and ecological
      niche modelling are used to characterize the various diploid and polyploid gene
      pools and unravel spatio-temporal patterns of gene flow among them. Key Results:
      On the diploid level, the three gene pools are clearly distinct between and
      within species of H. perforatum (two gene pools) and H. maculatum, and their
      divergence dates back to the first half of the Pleistocene. All polyploids in
      Central Europe show high levels of past and contemporary gene flow between all
      three gene pools. The correlation of genetic and geographical distances breaks
      down if the latter is larger than 250 km, indicating recent and ongoing gene
      flow. The two species are ecologically differentiated, but in particular hybrids
      among all three gene pools do not show significant niche differences compared to
      their parental gene pools, except for some combinations with H. maculatum.
      Conclusions: Inter- and intraspecific gene flow between inter- and intra-species
      gene pools is limited on the diploid level, and the geographical distribution of
      the diploids largely reflects Pleistocene evolutionary history. Secondary contact
      promoted hybridization and introgression on the polyploid level, enabling
      offspring to escape the diploid gene pools. However, the hybrid polyploids do not
      show significant niche differences compared to their diploid progenitors. It is
      concluded that the observed absence of niche divergence has precluded further
      differentiation and geographical partitioning of new polyploid lineages being
      effectively separated from the parental lines. The predominantly apomictic
      reproducing polyploids are trapped in the polyploid gene pool and the ecological
      climatic niche space of their diploid ancestors.

PMID- 29182724
TI  - Worsening Anxiety, Irritability, Insomnia, or Panic Predicts Poorer
      Antidepressant Treatment Outcomes: Clinical Utility and Validation of the Concise
      Associated Symptom Tracking (CAST) Scale.
AB  - Background: We report on the psychometric properties of the 16-item Concise
      Associated Symptom Tracking Scale self-report scale and its clinical utility.
      Methods: The 5-domain (irritability, anxiety, mania, insomnia, and panic)
      structure of Concise Associated Symptom Tracking Scale was validated with
      confirmatory factor analysis in Combining Medications to Enhance Depression
      Outcomes trial participants at baseline (n=664). Correlations with other clinical
      measures were used for convergent and divergent validity. In participants with at
      least one postbaseline visit (n=630), worsening in each Concise Associated
      Symptom Tracking Scale domain was defined as >=1.28 SD increase from baseline for
      each visit (weeks 1, 2, 4, and 6) only. Worsening in any domain (except mania)
      was defined as overall worsening. Association of domain-specific and overall
      worsening with remission was tested with logistic regression analyses. Results:
      The 5-domain structure had adequate model fit on confirmatory factor analysis
      (GFI=0.93, CFI=0.89, and RMSEA=0.07). Scores on anxiety, panic, insomnia, and
      mania significantly correlated with Hamilton Rating Scale for Depression anxiety
      subscale (rs=0.27), Psychiatric Diagnostic Screening Questionnaire-panic scale
      (rs=0.35), sum of 3 Quick Inventory of Depressive Symptomatology Self-Report
      insomnia items (rs=0.55), and Altman Self-Rating Mania scale (rs=0.41),
      respectively. From baseline to week 6, 5.2%, 7.5%, 47.6%, 15.6%, 6.2%, and 27.6%
      participants (n=630) experienced irritability, anxiety, mania, insomnia, panic,
      and overall worsening, respectively. Participants with overall worsening were
      less likely to remit (31.6%) than those without any worsening (43.9%; odds
      ratio=0.53, 95% CI=0.36, 0.78). Conclusion: The 16-item Concise Associated
      Symptom Tracking Scale self-report has acceptable psychometric properties.
      Clinically significant worsening of irritability, anxiety, insomnia, or panic
      with antidepressant treatment is associated with poorer outcomes.

PMID- 29182726
TI  - The association between income and life expectancy revisited:
      deindustrialization, incarceration and the widening health gap.
AB  - Background: The health gap between the top and the bottom of the income
      distribution is widening rapidly in the USA, but the lifespan of America's poor
      depends substantially on where they live. We ask whether two major developments
      in American society, deindustrialization and incarceration, can explain variation
      among states in life expectancy of those in the lowest income quartile. Methods:
      Life expectancy estimates at age 40 of those in the bottom income quartile were
      used to fit panel data models examining the relationship with deindustrialization
      and incarceration between 2001 and 2014 for all US states. Results: A one
      standard deviation (s.d.) increase in deindustrialization (mean = 11.2, s.d. =
      3.5) reduces life expectancy for the poor by 0.255 years [95% confidence interval
      (CI): 0.090-0.419] and each additional prisoner per 1000 residents (mean = 4.0,
      s.d. = 1.5) is associated with a loss of 0.468 years (95% CI: 0.213-0.723). Our
      predictors explain over 20% of the state-level variation in life expectancy among
      the poor and virtually the entire increase in the life expectancy gap between the
      top and the bottom income quartiles since the turn of the century. Conclusions:
      In the USA between 2001 and 2014, deindustrialization and incarceration
      subtracted roughly 2.5 years from the lifespan of the poor, pointing to their
      role as major health determinants. Future research must remain conscious of the
      upstream determinants and the political economy of public health. If public
      policy responses to growing health inequalities are to be effective, they must
      consider strengthening industrial policy and ending hyper-incarceration.

PMID- 29182725
TI  - Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New
      Zealand.
AB  - Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to
      public health. No studies to date have examined the genomic epidemiology of
      gonorrhoea in the Western Pacific Region, where the incidence of gonorrhoea is
      particularly high. Methods: A population-level study of N. gonorrhoeae in New
      Zealand (October 2014 to May 2015). Comprehensive susceptibility testing and WGS
      data were obtained for 398 isolates. Relatedness was inferred using phylogenetic
      trees, and pairwise core SNPs. Mutations and genes known to be associated with
      resistance were identified, and correlated with phenotype. Results: Eleven
      clusters were identified. In six of these clusters, >25% of isolates were from
      females, while in eight of them, >15% of isolates were from females. Drug
      resistance was common; 98%, 32% and 68% of isolates were non-susceptible to
      penicillin, ciprofloxacin and tetracycline, respectively. Elevated MICs to
      extended-spectrum cephalosporins (ESCs) were observed in 3.5% of isolates
      (cefixime MICs >= 0.12 mg/L, ceftriaxone MICs >= 0.06 mg/L). Only nine isolates
      had penA XXXIV genotypes, three of which had decreased susceptibility to ESCs
      (MIC = 0.12 mg/L). Azithromycin non-susceptibility was identified in 43 isolates
      (10.8%); two of these isolates had 23S mutations (C2611T, 4/4 alleles), while all
      had mutations in mtrR or its promoter. Conclusions: The high proportion of
      females in clusters suggests transmission is not exclusively among MSM in New
      Zealand; re-assessment of risk factors for transmission may be warranted in this
      context. As elevated MICs of ESCs and/or azithromycin were found in closely
      related strains, targeted public health interventions to halt transmission are
      urgently needed.

PMID- 29182727
TI  - An Ambulatory Polysomnography Study of the Post-traumatic Nightmares of Post
      traumatic Stress Disorder.
AB  - Study Objectives: This study used ambulatory polysomnography (PSG) to investigate
      post-traumatic nightmares of post-traumatic stress disorder (PTSD). The key
      research question was whether post-traumatic nightmares occur in both rapid eye
      movement (REM) and non-REM sleep, and if so, whether nightmares in each sleep
      stage differed in content, phenomenology, and heart rate response. Underlying
      sleep disorders were investigated in an exploratory way. Methods: Thirty-five
      treatment-seeking veterans, current serving military members, and emergency
      service personnel undertook full PSG using the Compumedics (Melbourne, Australia)
      SomtePSG V1 system, during an inpatient psychiatric admission. The PSG recording
      included an event button to be pressed when a nightmare occurred, allowing us to
      determine the stage of sleep, changes in heart rate, and associated sleep events.
      The content and phenomenological features of participants' nightmares were
      recorded. Results: Of the 35 participants, 29 reported a nightmare during their
      sleep study, but only 21 pressed the event button and could recall the content of
      one or more nightmare. This yielded sleep and nightmare data for 24 nightmares.
      Of the 24, 10 nightmares arose from REM sleep and 14 from non-REM (stages N1 and
      N2). Seven were accurate trauma replays and 17 were non-replay or a mixture of
      replay and non-replay. Most nightmares were associated with respiratory or leg
      movement events and increase in heart rate on awakening. Conclusions: Post
      traumatic nightmares of PTSD occur in both REM and non-REM sleep and are commonly
      associated with other sleep disturbances. These findings have important treatment
      implications.

PMID- 29182728
TI  - An evaluation of the impact of aloe vera and licorice extracts on the course of
      experimental pigeon paramyxovirus type 1 infection in pigeons.
AB  - The progressive decrease in the efficiency of synthetic drugs has prompted
      research into phytogenic feed additives with potentially immunomodulatory and
      anti-infective properties. Complex diseases with a mixed etiology, including
      viral, pose a growing problem in domestic pigeons. The aim of this study was to
      determine the effectiveness of various doses of aloe vera and licorice extracts
      on the course of experimental PPMV-1 infection in pigeons. The experiment was
      performed on pigeons divided into 5 groups, including one control group and 4
      experimental groups, which were orally administered aloe vera or licorice
      extracts at 300 or 500 mg/kg BW for 7 d after experimental inoculation with PPMV
      1. On d 4, 7, and 14 after inoculation, cloacal swabs and samples of organs were
      collected from 4 birds in each group. The samples were analyzed to determine the
      copy number of PPMV-1 RNA by TaqMan qPCR. The results indicate that licorice and
      aloe vera extracts inhibited PPMV-1 replication by decreasing viral RNA copy
      numbers in the examined organs. The most inhibitory effect was observed in
      pigeons receiving aloe vera extract at 300 mg/kg BW, for which PPMV-1 RNA copy
      numbers were approximately 7-fold lower (brain), 9-fold lower (kidneys), and 14
      fold lower (liver) than in the control group. The results of this study point to
      the potentially antiviral effects of aloe vera and licorice extracts in pigeons
      infected with PPMV-1. To the best of our knowledge, this is the first study to
      investigate the antiviral properties of aloe vera and licorice extracts in
      domestic pigeons.

PMID- 29182729
TI  - Effects of Opioids Given to Facilitate Mechanical Ventilation on Sleep Apnea
      After Extubation in the Intensive Care Unit.
AB  - Study Objectives: Following extubation in the intensive care unit (ICU), upper
      airway (UA) edema and respiratory depressants may promote UA dysfunction. We
      tested the hypothesis that opioids increase the risk of sleep apnea early after
      extubation. Methods: Fifty-six ICU patients underwent polysomnography the night
      after extubation. Airflow limitation during wakefulness was identified using
      bedside spirometry. Correlation and ordinal regression analyses were used to
      quantify the effects of preextubation opioid dose on postextubation apnea
      hypopnea index (AHI) and severity of sleep apnea and whether or not inspiratory
      airway obstruction (ratio of maximum expiratory and inspiratory airflows at 50%
      of vital capacity [MEF50/MIF50] >= 1) during wakefulness predicts airway
      obstruction during sleep. Data were adjusted for age, gender, body mass index, as
      well as a generalized propensity score balanced for APACHE II, score for
      preoperative prediction of obstructive sleep apnea, duration of mechanical
      ventilation, chronic obstructive pulmonary disease, and a procedural severity
      score for morbidity. Results: Sleep apnea (AHI >= 5) was present in 40 (71%) of
      the 56 patients. Morphine equivalent dose given 24 hours prior extubation
      predicted obstructive respiratory events during sleep (r = 0.35, p = .01) and
      sleep apnea (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.02-1.34). Signs
      of inspiratory UA obstruction (MEF50/MIF50 >= 1) assessed by bedside spirometry
      were strongly associated with sleep apnea (OR 5.93; 95% CI 1.16-30.33).
      Conclusions: High opioid dose given 24 hours prior to extubation increases the
      likelihood of postextubation sleep apnea in the ICU, particularly in patients
      with anatomical vulnerability following extubation.

PMID- 29182730
TI  - Genetic Variation in SLC8A1 Gene Involved in Blood Pressure Responses to Acute
      Salt Loading.
AB  - BACKGROUND: Salt sensitivity of blood pressure (SSBP) increases the risk of
      cardiovascular complications, and the heritability of SSBP is about 50% in
      Chinese population. However, studies identifying genes involved in BP responses
      to acute sodium loading and diuresis shrinkage are still limited. METHOD: A total
      of 342 essential hypertensives from Beijing were recruited in our study. A
      modified Sullivan's acute oral saline load and diuresis shrinkage test was
      conducted to each individual. Medical history and lifestyle risk factors were
      obtained by questionnaire. Generalized linear model was used to examine the
      associations of 29 single-nucleotide polymorphisms (SNPs) with SSBP and false
      discovery rate (FDR) was used to correct P values for multiple testing. RESULTS:
      In the process of acute sodium loading, after adjusting for age and 24-hour
      urinary sodium concentration, SNPs in CYP11B2, PRKG1, SLC8A1 genes were
      significantly associated with systolic BP (SBP) rising in the additive and
      recessive model; SNPs in CYP4A11, PRKG1, SLC8A1, and ADRB2 genes were
      significantly associated with diastolic BP (DBP) rising. In the process of
      diuresis shrinkage, SNPs of CLCNKA, eNOS, PRKG1 gene were associated with SBP and
      DBP decreasing. After FDR correction, rs434082 in SLC8A1 gene was still
      significantly associated with blood pressure rising during salt load. In the
      additive model, A allele increased DBP of 2.8 mm Hg (FDR_q = 0.029) and MAP of
      3.1 mm Hg (FDR_q = 0.029) after adjusting for age and 24-hour urinary sodium
      concentration. CONCLUSION: SLC8A1 gene may contribute to BP change in the process
      of acute sodium loading in a Han Chinese population.

PMID- 29182731
TI  - The Association Between Serum Activin A Levels and Hypertension in the Elderly: A
      Cross-Sectional Analysis From I-Lan Longitudinal Aging Study.
AB  - BACKGROUND: Hypertension is an important risk factor for cardiovascular disease.
      Activin A, a member of the transforming growth factor-beta cytokine family, has
      been shown to regulate blood pressure through the renin-angiotensin system.
      However, the relationship between activin A and blood pressure remains uncertain.
      The objective of this study was to determine whether serum activin A levels are
      associated with blood pressure. METHOD: A total of 470 participants of I-Lan
      longitudinal Aging Study (ILAS) were eligible for this study. Serum levels of
      activin A were assessed by enzyme-linked immunosorbent assay. Cross-sectional
      analyses were performed, including comparisons of demographic characteristics,
      hypertensive status, and activin A levels. RESULTS: Among the study participants
      (50% men, mean age, 69 years), 236 (50.2%) were hypertensive and 234 (49.8%) were
      normotensive. Hypertensive patients had significantly higher serum activin A
      levels than normotensives (normotensive vs. hypertensive: 507 +/- 169 vs. 554 +/-
      176 pg/ml, mean +/- SD, P < 0.001). All subjects were divided into 3 tertiles on
      the basis of serum activin A levels. Increasing tertiles of activin A were
      associated with higher systolic blood pressure (SBP), diastolic blood pressure
      and pulse pressure (PP) (all P < 0.001). After adjusting for all the potential
      confounding factors, serum activin A concentration was still significantly
      associated with SBP (P = 0.02) and PP (P = 0.03). CONCLUSIONS: Serum activin A
      level was associated with SBP and PP. Further studies are required to assess
      their causal relationship and the clinical relevance.

PMID- 29182732
TI  - A National Survey of Assertive Outreach Treatment Services for People Who
      Frequently Attend Hospital due to Alcohol-Related Reasons in England.
AB  - Aims: To characterize England's alcohol assertive outreach treatment (AAOT)
      services for people who frequently attend hospital due to alcohol-related reasons
      according to their concordance with six core AAOT components. Methods: A cross
      sectional national survey using structured telephone interviews with health
      professionals examining 6 essential AAOT components. High-level AAOT services
      were those that delivered 5 or more components, mid-level 3 to 4 components, low
      level AAOT services 2 or less. Results: The analysis included 37 services that
      were classified according to their concordance with the 6 AAOT components. Six
      were identified as high-level AAOT services, 13 as mid-level AAOT services and 18
      as low-level services. Extended support covering housing, mental and physical
      health over and above alcohol consumption was the most commonly delivered AAOT
      component provided. Having a multidisciplinary team was the least observed
      component, delivered in 33% high-level AAOT services and in 15% mid-level AAOT
      services. None of the low-level AAOT services had a multidisciplinary team.
      Conclusions: Access to AAOT services developed to support high-cost and high
      needs frequent hospital attenders varies across the nation. Further research,
      service evaluation and AAOT implementation should focus on essential AAOT
      components rather than self-defined labels of AAOT. Short summary: The study
      investigated alcohol assertive outreach treatment (AAOT) services in England. The
      study found variability in service provision across AAOT services when measured
      against six essential AAOT components. Improvement of AAOT in England's hospitals
      should focus on the implementation of essential AAOT components.

PMID- 29182733
TI  - Corrigendum: STOPP/START criteria for potentially inappropriate prescribing in
      older people: version 2.

PMID- 29182734
TI  - Quality of life measured with EuroQol-five dimensions questionnaire predicts long
      term mortality, response, and reverse remodelling in cardiac resynchronization
      therapy patients.
AB  - Aims: There are previous studies on quality of life (QoL) in cardiac
      resynchronization therapy (CRT) patients; however, there are no data with the
      short EuroQol-five dimensions (EQ-5D) questionnaire predicting outcomes. We aimed
      to assess the predictive role of baseline QoL and QoL change at 6 months after
      CRT with EQ-5D on 5-year mortality and response. Methods and results: In our
      prospective follow-up study, 130 heart failure (HF) patients undergoing CRT were
      enrolled. Clinical evaluation, echocardiography, and EQ-5D were performed at
      baseline and at 6 months of follow-up, continued to 5 years. Primary endpoint was
      all-cause mortality at 5 years. Secondary endpoints were (i) clinical response
      with at least one class improvement in New York Heart Association without HF
      hospitalization and (ii) reverse remodelling with 15% reduction in left
      ventricular end-systolic volume at 6 months. Fifty-four (41.5%) patients died
      during 5 years, 85 (65.3%) clinical responders were identified, and 63 patients
      (48.5%) had reverse remodelling. Baseline issues with mobility were associated
      with lower response [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.16
      0.84; P = 0.018]. Lack of reverse remodelling correlated with self-care issues at
      baseline (OR 0.10, 95% CI 0.01-0.94; P = 0.04). Furthermore, self-care
      difficulties [hazard ratio (HR) 2.39, 95% CI 1.17-4.86; P = 0.01) or more anxiety
      (HR 1.51, 95% CI 1.00-2.26; P = 0.04) predicted worse long-term survival. At 6
      months, mobility (HR 3.95, 95% CI 1.89-8.20; P < 0.001), self-care (HR 7.69, 95%
      CI 2.23-25.9; P = 0.001), or >= 10% visual analogue scale (VAS) (HR 2.24, 95% CI
      1.27-3.94; P = 0.005) improvement anticipated better survival at 5 years.
      Conclusion: EuroQol-five dimension is a simple method assessing QoL in CRT
      population. Mobility issues at baseline are associated with lower clinical
      response, whereas self-care issues predict lack of reverse remodelling. Problems
      with mobility or anxiety before CRT and persistent issues with mobility, self
      care, and VAS scale at 6 months predict adverse outcome.

PMID- 29182735
TI  - Never smokers with resected lung cancer: different demographics, similar
      survival.
AB  - OBJECTIVES: We sought to examine changes over time in the proportion of never
      smokers among surgical lung cancer patients and to determine whether smoking
      history affected survival. METHODS: We performed a retrospective review of a
      prospective database. Among never smokers and smokers, demographic and
      pathological data were compared. Disease-free survival (DFS) and cancer-specific
      survival (CSS) were analysed. Propensity matching was performed for further
      comparison of survival in a matched cohort. RESULTS: Among 3232 patients, we
      identified 718 never smokers (22%), 993 smokers with <30 pack history (31%) and
      1521 smokers with >=30 pack history (47%). The proportion of never smokers
      increased over time, comprising 26.6% of the cohort after 2007 compared with
      16.1% prior thereto (P <= 0.001). Never smokers were younger, more likely to be
      women and Asian, more frequently had adenocarcinoma and lower lobe tumours and
      were more likely to have pStage I disease. In pStage-matched cohorts, there were
      no differences in DFS or CSS. Similarly, in propensity-matched groups (498
      patients each), there was no difference in 5-year DFS (66% vs 67%, P = 0.661) or
      in CSS (84% vs 81%, P = 0.350). On univariate analysis of the matched cohort,
      never smoking status had no effect on DFS (hazard ratio 1.05, P = 0.661) or CSS
      (hazard ratio 1.16, P = 0.350). CONCLUSIONS: The proportion of never smokers
      undergoing resections for lung cancer is increasing. Never smokers have distinct
      demographic patterns and tend to be younger women with adenocarcinoma. Despite
      these differences, stage and propensity-matched never smokers have the same
      survival as smokers and remain at equal risk for recurrence and death.

PMID- 29182736
TI  - Does septal thickness influence outcome of myectomy for hypertrophic obstructive
      cardiomyopathy?
AB  - OBJECTIVES: Patients with hypertrophic obstructive cardiomyopathy and basal
      septal thickness <18 mm are often considered unsuitable candidates for myectomy.
      Mitral valve (MV) replacement is frequently performed instead. We aimed to
      determine whether septal thickness affects outcomes and adequacy of myectomy.
      METHODS: Clinical and echocardiographic data were reviewed for 1486 consecutive
      adult patients with hypertrophic obstructive cardiomyopathy who underwent
      transaortic septal myectomy from January 2005 through December 2014. Comparisons
      between patients, grouped by septal thickness (<18 mm, n = 369; 18-21 mm, n = 612
      and >21 mm, n = 505), were performed with the Kruskal-Wallis and the Pearson chi2
      tests and semiparametric analysis of covariance. RESULTS: Median group ages were
      57, 57 and 54 years (P = 0.007); men comprised 50.4%, 56.7% and 62.0%,
      respectively (P = 0.003). Intrinsic MV disease was present in 5.9%, 5.2% and
      4.6%, respectively (P = 0.80). All patients underwent transaortic septal
      myectomy. Additional mitral procedures were performed in 7.6%, 7.8% and 8.1%,
      respectively (P = 0.90). Reasons for MV surgery included intrinsic MV disease
      (66.7%), residual mitral regurgitation (30.8%) and residual gradient (2.6%). All
      groups had postoperative gradient relief (median reduction: 51, 54 and 50 mmHg; P
      = 0.11). Ventricular septal defect occurred in 4 patients (0.3%), and risk did
      not differ by group (P = 0.24). CONCLUSIONS: Adequate relief of left ventricular
      outflow tract obstruction can be achieved via transaortic septal myectomy without
      concomitant MV procedures when septal thickness is < 18 mm, and the risk of
      ventricular septal defect is minimal. Concomitant MV repair/replacement should be
      reserved for patients with intrinsic MV disease or inadequate relief of mitral
      regurgitation/left ventricular outflow tract obstruction following adequate
      extended septal myectomy.

PMID- 29182737
TI  - Health-related knowledge, beliefs and self-efficacy in women with polycystic
      ovary syndrome.
AB  - STUDY QUESTION: Do health-related knowledge, beliefs and self-efficacy differ
      between women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER:
      Women with PCOS felt at greater risk for adverse health outcomes, yet believed a
      healthy lifestyle was less beneficial to prevent weight gain relative to a
      comparison group. WHAT IS KNOWN ALREADY: Diet and physical activity are often
      used to treat PCOS, but there are high attrition rates and less engagement in
      self-help methods. It is unclear whether there are unique psychosocial
      considerations in PCOS that should be incorporated into these interventions.
      STUDY DESIGN, SIZE, DURATION: This cross-sectional study enrolled 475 women with
      (N = 255) and without PCOS (N = 220). PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Female participants were recruited through paper and web-based advertisements
      across the US (mean age: 28.1 +/- 5.4 years). Participants were either diagnosed
      with PCOS by a healthcare professional (PCOS group) or had self-reported regular
      menstrual cycles (comparison group). A reliable and valid online instrument about
      health-related knowledge, beliefs and self-efficacy was administered to these
      participants. MAIN RESULTS AND THE ROLE OF CHANCE: Most women with PCOS had a
      basic understanding of nutrition (96%), but had misconceptions about diagnostic
      criteria for PCOS (>=86%). PCOS was associated with greater perceived
      susceptibility for disease and weight gain and poorer perceived control over
      these health outcomes (all P < 0.05), in relation to the comparison group. Women
      with PCOS also perceived fewer benefits of healthy behaviors on weight gain (P =
      0.03) with less than half of the PCOS group attempting to follow government diet
      recommendations (47%). There were no differences in the self-efficacy of dietary
      behaviors between groups. LIMITATIONS, REASONS FOR CAUTION: It is likely that
      participant self-selection occurred due to the nature of recruitment in this
      study and results may have limited generalizability since most participants
      identified as Caucasian. Additionally, it is unclear whether some results may be
      clinically meaningful due to small effect sizes. WIDER IMPLICATIONS OF THE
      FINDINGS: These findings support that behavioral interventions should incorporate
      the unique psychosocial considerations associated with PCOS to encourage patient
      participation in lifestyle interventions. STUDY FUNDING/COMPETING INTEREST(S):
      This manuscript was partially supported by Cornell University Human Ecology
      Alumni Association and College of Agriculture and Life Sciences Alumni
      Association. The authors have no competing interests. TRIAL REGISTRATION NUMBER:
      NCT01859663.

PMID- 29182738
TI  - Protective role of the co-stimulator CD27 receptor and regulatory T cells in
      early atherogenesis.

PMID- 29182739
TI  - The search for cardiovascular benefit from treating obstructive sleep apnoea with
      CPAP therapy.

PMID- 29182741
TI  - Off-label use of thoracic aortic endovascular stent grafts to simplify difficult
      resections and procedures in general thoracic surgery.
AB  - OBJECTIVES: Tumour infiltration, or gross infectious involvement of the thoracic
      aortic wall, poses a significant intraoperative risk for fatal bleeding and
      therefore could compromise adequate resection or efficient surgical management of
      pleural infection in a considerable amount of cases. We present 3 successful
      cases of off-label thoracic aortic endografting to safeguard thoracic aortic wall
      integrity. METHODS: After all patients received thoracic stent grafts through
      femoral access into the descending aorta, the first patient underwent a resection
      of a locally advanced squamous cell carcinoma of the left inferior lobe cT4cN0
      1cM0 after neoadjuvant chemoradiation, which had infiltrated the descending
      aortic wall. The second case was video-assisted thoracoscopic bilateral pleural
      decortication for empyema with aortic ulcers of the distal thoracic aorta in a
      patient with pancreatic intrathoracic fistula in a necrotizing pancreatitis. The
      third patient was operated for a locally advanced squamous cell carcinoma of the
      left inferior lobe initial stage cT4 cN1-2 cM0 after neoadjuvant chemoradiation,
      which had broad contact to the descending aorta at the level of thoracic
      vertebrae 7 and 8 on a circumference of circa 180 degrees . Regional ethics
      committee approval according the Swiss Federal Human Research Act was obtained
      according to regulations. RESULTS: Preventive stent graft placement resulted in
      complication-free resection and significantly minimized the risk of fatal
      intraoperative bleeding. Patients were thus not exposed to complications
      associated with aortic cross-clamping, possible prosthetic replacement and
      extracorporeal circulation techniques. CONCLUSIONS: In carefully selected patient
      populations, the resection of locally advanced tumours or infectious processes
      involving the aortic wall can be facilitated by thoracic endovascular aortic
      repair prior to resection.

PMID- 29182740
TI  - Speciation Generates Mosaic Genomes in Kangaroos.
AB  - The iconic Australasian kangaroos and wallabies represent a successful marsupial
      radiation. However, the evolutionary relationship within the two genera, Macropus
      and Wallabia, is controversial: mitochondrial and nuclear genes, and
      morphological data have produced conflicting scenarios regarding the phylogenetic
      relationships, which in turn impact the classification and taxonomy. We sequenced
      and analyzed the genomes of 11 kangaroos to investigate the evolutionary cause of
      the observed phylogenetic conflict. A multilocus coalescent analysis using
      ~14,900 genome fragments, each 10 kb long, significantly resolved the species
      relationships between and among the sister-genera Macropus and Wallabia. The
      phylogenomic approach reconstructed the swamp wallaby (Wallabia) as nested inside
      Macropus, making this genus paraphyletic. However, the phylogenomic analyses
      indicate multiple conflicting phylogenetic signals in the swamp wallaby genome.
      This is interpreted as at least one introgression event between the ancestor of
      the genus Wallabia and a now extinct ghost lineage outside the genus Macropus.
      Additional phylogenetic signals must therefore be caused by incomplete lineage
      sorting and/or introgression, but available statistical methods cannot
      convincingly disentangle the two processes. In addition, the relationships inside
      the Macropus subgenus M. (Notamacropus) represent a hard polytomy. Thus, the
      relationships between tammar, red-necked, agile, and parma wallabies remain
      unresolvable even with whole-genome data. Even if most methods resolve
      bifurcating trees from genomic data, hard polytomies, incomplete lineage sorting,
      and introgression complicate the interpretation of the phylogeny and thus
      taxonomy.

PMID- 29182742
TI  - Lack of HIV testing and dissatisfaction with HIV testing and counselling among
      men having sex with men in Hungary.
AB  - Background: Using data from a large internet-based survey of European men having
      sex with men (MSM), we assessed factors associated with HIV testing and reasons
      for dissatisfaction with HIV testing and counselling among Hungarian MSM.
      Methods: A total of 2052 Hungarian MSM provided evaluable data for the European
      MSM Internet Survey (EMIS) in 2010. chi2 tests and Poisson regression with a
      robust variance estimator were used to assess factors associated with HIV testing
      and dissatisfaction with HIV testing and counselling. Results: A total of 42.1%
      of MSM reported never being testing for HIV. Over one-half of men (54.1%) who
      reported condomless anal intercourse (CAI) in the prior 12 months with a person
      of unknown or sero-discordant HIV status reported no lifetime HIV testing. The
      factor most strongly associated with dissatisfaction with HIV testing and
      counselling was test site with increased dissatisfaction with inpatient hospital
      settings vs. community-based organizations. Both lack of HIV testing and
      dissatisfaction with testing were independently associated with MSM who reported
      that no one, or only a few people, knew they were attracted to men. Conclusions:
      Lack of HIV testing was strongly associated with CAI. MSM reported that community
      based organizations better supported confidentiality and were more respectful
      during HIV testing.

PMID- 29182743
TI  - A Roadmap to Implementing Antimicrobial Stewardship Principles in Long-term Care
      Facilities (LTCFs): Collaboration Between an Acute-Care Hospital and LTCFs.
AB  - Effective 28 November 2017, the Centers for Medicare & Medicaid Services (CMS)
      mandated long-term care facilities (LTCFs) to have antimicrobial stewardship
      programs (ASPs) in place. Although guidance exists for establishing ASPs in
      LTCFs, limited data exist on the "how." As comprehensive ASPs already exist in
      many acute-care hospitals (ACHs) and with the known "sharing of patients" between
      both settings, extending ACH ASP expertise to LTCFs will not only aid LTCFs in
      complying with the CMS mandate but will likely also facilitate in decreasing
      multidrug-resistant organisms and Clostridium difficile infection rates in
      patients at both organizations. Here, we provide a roadmap on how to implement
      ASPs in LTCFs, using examples from our own ACH's collaboration with local LTCFs
      to develop and sustain LTCF ASPs. We discuss critical elements to achieving
      successful LTCF ASPs, including the potential barriers and how to overcome them.

PMID- 29182744
TI  - The Value of the Middle Meningeal Artery in Cerebrovascular Bypass Surgery: An
      Anatomic Feasibility Study.
AB  - BACKGROUND: Over the past decade, there has been a revival and a renewed interest
      for cerebrovascular bypass procedures. The superficial temporal artery (STA) has
      its value as a reliable donor vessel; however, a possible role for the middle
      meningeal artery (MMA) as a donor artery is still unclear. OBJECTIVE: To assess
      the feasibility of using the MMA as a donor vessel in cerebrovascular surgery.
      METHODS: We performed cadaveric dissections on 12 fresh specimens (23 sides)
      after bilateral silicone injection into the internal and external carotid
      arteries. We compared the size, diameter, and possibility to perform a bypass to
      the middle cerebral artery for both the MMA and the STA. Measurements were done
      using an electrical caliper. Additional measurements of the MMA and STA were
      performed on 20 random angiograms. RESULTS: There was no statistically
      significant difference in diameter of the MMA at its ostium being 2.4 mm,
      compared to 2.7 mm for the STA ostium (t-test; P = .21). The MMA could be
      mobilized over 4.1 cm, whereas the STA over 8.3 cm. Finally, the mean diameter of
      the donor vessel at the site of the anastomosis was 1.6 mm versus 1.9 mm for MMA
      and STA, respectively (P = .0026). We were able to perform an MMA and middle
      cerebral artery anastomosis on 17 sides. CONCLUSION: These results suggest that
      the MMA is a potentially valuable donor vessel to be used in selected cases. The
      availability of a suitable MMA branch should be assessed preoperatively on the
      angiogram.

PMID- 29182745
TI  - Unmet need for primary prevention in individuals with hypertriglyceridaemia not
      eligible for statin therapy according to European Society of Cardiology/European
      Atherosclerosis Society guidelines: a contemporary population-based study.
AB  - Aims: To identify individuals at high risk of atherosclerotic cardiovascular
      disease (ASCVD), who are not definite statin eligible according to the 2016
      European Society of Cardiology/European Atherosclerosis Society (ESC/EAS)
      guidelines, based on high concentrations of plasma triglycerides. Methods and
      results: From the Copenhagen General Population Study (2003-2015) 58 547
      individuals aged 40-65 and free of ASCVD, diabetes, and statin use at baseline
      were included. Of these, 14% were definite statin eligible, 7% were not eligible
      and had triglycerides >=3.0 mmol/L (264 mg/dL), and 79% were not statin eligible
      and had triglycerides <3.0 mmol/L (264 mg/dL). During 456 057 person-years of
      follow-up, 1770 individuals experienced a major adverse cardiovascular event
      (MACE) and 734 experienced a myocardial infarction (MI). The cumulative
      incidences of MACE at age 70 were 8.1% (95% confidence interval 7.3-8.9%) and
      14.6% (12.6-16.8%) in statin non-eligible individuals with triglycerides <3.0
      mmol/L (264 mg/dL) and >=3.0 mmol/L (264 mg/dL), and 16.5% (14.0-19.3%) in statin
      eligible individuals. Corresponding cumulative incidences of MI were 3.0% (2.7
      3.3%), 7.8% (6.4-9.5%), and 7.1% (5.9-8.4%), respectively. The estimated 10-year
      risks of MACE were 2.8% (2.6-3.0%) and 5.7% (4.9-6.6%) in statin non-eligible
      individuals with triglycerides <3.0 mmol/L (264 mg/dL) and >=3.0 mmol/L (264
      mg/dL), and 7.6% (6.9-8.3%) in statin eligible individuals; the median age in
      these three groups were 51, 51, and 60 years, respectively. Corresponding risks
      of MI were 1.0% (0.9-1.1%), 3.0% (2.4-3.7%), and 3.3% (2.8-3.7%), respectively.
      Conclusion: Statin non-eligible individuals with triglycerides >=3.0 mmol/L (264
      mg/dL) had risk of ASCVD similar to statin eligible individuals, defined
      according to the 2016 ESC/EAS guidelines. This illustrates an unmet need for
      primary prevention, calling for expansion of guidelines on statin eligibility,
      and the potential for placebo-controlled randomized clinical trials in
      individuals with hypertriglyceridaemia.

PMID- 29182746
TI  - Experiences of Persons With Parkinson's Disease Engaged in Group Therapeutic
      Singing.
AB  - Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder
      that leads to altered neural control of movement, including the control of voice,
      respiration, and swallowing. There is a prevalent need to provide therapy for
      voice, respiration, and swallowing difficulties because current pharmacological
      and surgical treatments do not effectively treat these impairments. Previous
      research has demonstrated that singing may be a treatment option to target voice,
      respiratory, and swallowing impairments, as well as quality of life. However,
      participants' perspectives related to reasons for enrolling and engaging in
      programs as well as evaluation of singing programs have been neglected.
      Objective: The purpose of this descriptive study was thus to solicit
      participants' views of their involvement in a group singing intervention (GSI)
      led by credentialed music therapists. Methods: Twenty persons with PD were
      interviewed 4 to 6 months after completing the singing intervention. Participants
      were asked about 1) why they chose to participate, 2) what were the beneficial
      and non-beneficial aspects of participating, and 3) how to improve overall design
      and delivery of the GSI. Results: Using content analysis procedures, we learned
      that participants regarded their involvement in the study as mutually beneficial,
      fun, and engaging. Participants appreciated the fellowship with other persons
      with PD and offered minimal constructive criticism. Conclusions: This study
      provided greater insight into how a therapeutic singing program may benefit
      participants and positively impact their lives.

PMID- 29182747
TI  - Improving outcomes after catheter ablation of atrial fibrillation: better patient
      selection, better procedure, or both?

PMID- 29182749
TI  - Infectious Diseases Society of America (IDSA) POSITION STATEMENT: Why IDSA Did
      Not Endorse the Surviving Sepsis Campaign Guidelines.
AB  - IDSA did not endorse the 2016 Surviving Sepsis Campaign Guidelines despite being
      represented in the working group that drafted the guidelines document. Leadership
      from the IDSA, the Surviving Sepsis Campaign Guidelines, and the Society of
      Critical Care Medicine had numerous amicable discussions primarily regarding the
      bolded, rated guidelines recommendations. Our societies had different
      perspectives, however, regarding the interpretation of the major studies that
      informed the guidelines' recommendations, thus leading us to different
      conclusions and different perspectives on the recommendations. IDSA consequently
      elected not to endorse the guidelines. IDSA nonetheless hopes to be able to
      continue collaborating with the Surviving Sepsis Campaign and the Society of
      Critical Care Medicine to resolve our differences and to develop further
      strategies together to prevent sepsis and septic shock as well as reduce death
      and disability from these conditions both nationally and globally.

PMID- 29182748
TI  - Phrenic nerve injury during right inferior pulmonary vein ablation with the
      second-generation cryoballoon: clinical, procedural, and anatomical
      characteristics.
AB  - Aims: There is still sparse information regarding phrenic nerve injury (PNI)
      during ablation of the right inferior pulmonary vein (RIPV) by means of the
      second-generation cryoballoon advance (CB-A). The aim of this study was to
      describe the procedural, anatomical, and clinical characteristics of patients who
      experienced PNI during the RIPV ablation. Methods and results: Consecutive
      patients who had undergone pulmonary vein isolation (PVI) using CB-A and suffered
      PNI during RIPV ablation were retrospectively included in our study. A cohort of
      patients who did not suffer any PNI was randomly included in a 1:3 ratio as a
      control group. The incidence of PNI during RIPV cryoapplication was 3.5%, (34 of
      979 patients). There were no significant differences in clinical characteristics
      between patients with and without PNI. The prevalence of right common ostium
      (RCO) was significantly higher in patients with a PNI [4 patients (11.8%) vs. 1
      patient (1.0%); P < 0.01]. A temperature drop velocity from the basal temperature
      to - 20  degrees C of 2.38  degrees C/s rendered a sensitivity of 82.4% and a
      specificity of 51.0% with a negative predictive value of 89.7%. Temperature drop
      velocity from basal to - 20  degrees C and the presence of an RCO were predictors
      of PNI in the multivariate analysis [odds ratio (OR) 7.27, 95% confidence
      interval (CI) 2.54-20.80; P < 0.01 and OR 18.41, 95%CI 1.87-181.23; P = 0.01,
      respectively). Conclusion: PNI during RIPV freeze might occur in around 3.5% of
      cases. The presence of an RCO and a fast temperature drop must prompt a careful
      monitoring of the phrenic nerve function during cryoapplications on the RIPV.

PMID- 29182750
TI  - Capsule Endoscopy Validation of the Magnetic Enterography Global Score in
      Patients with Established Crohn's Disease.
AB  - Background and Aims: Capsule endoscopy [CE] and magnetic resonance enterography
      [MRE] are prime modalities for evaluation of the small bowel in Crohn's disease
      [CD]. Detection of proximal small bowel [SB] inflammation in CD by MRE is
      challenging. Currently available quantitative MRE scores do not incorporate
      proximal SB data. The MRE global score [MEGS] was designed for quantitative
      evaluation of the entire digestive tract; its accuracy in the proximal SB has not
      previously been evaluated. This study compared the evaluation of the small bowel
      inflammation by MEGS and CE-derived quantitative score (the Lewis score[LS]).
      Methods: CD patients in stable clinical remission were prospectively recruited
      and underwent MRE and CE; faecal calprotectin [FC] levels were obtained. MEGS was
      calculated for each SB segment and the entire SB [SBMEGS]. SB inflammation on CE
      was quantified using LS. A cumulative Lewis score [C-LS] was calculated based on
      summation of three tertiles scores. Results: Fifty patients were included. There
      was a significant correlation of SBMEGS with LS and C-LS [r = 0.61 and 0.71, both
      p = 0.001]. The correlation with FC was stronger for MEGS than for LS or C-LS [r
      = 0.68 vs r = 0.46 vs r = 0.53, all p = 0.001]. The correlation between the
      proximal LS and MEGS was significant [r = 0.55, p = 0.001]; median MEGS was
      significantly different in patients, with LS values consistent with mucosal
      healing, mild and moderate-to-severe inflammation. Conclusions: MEGS provides
      accurate evaluation of the SB and strongly correlates with FC; the main advantage
      of MEGS is the accurate quantification of proximal SB inflammation unavailable
      for alternative MRE scores.

PMID- 29182751
TI  - Adverse childhood experiences and access and utilization of health care.
AB  - Background: Adverse childhood experiences (ACEs) have been associated with a
      variety of negative health outcomes. However, the association between ACEs and
      access and utilization of health care have been largely ignored. Methods: This
      study examined data from the 2011 Behavioral Risk Factor Surveillance System (N =
      101 527). We conducted logistic regression analyses, with nine ACEs as
      independent variables, in relation to the odds of being insured, having a
      personal health care provider and receiving a physician checkup in the past year.
      Unadjusted and adjusted multivariable models were estimated. Results: After
      accounting for potential confounders, all ACEs were associated with lower odds of
      being currently insured and receiving a physician checkup in the past year.
      Physical abuse, emotional abuse and several measures of household dysfunction
      were associated with lower odds of having a personal provider. Conclusions: Our
      findings suggest potential pathways by which ACEs may impact health. Provision of
      health insurance and providing care in a trauma-informed manner should be
      considered for individuals with a history of ACEs.

PMID- 29182752
TI  - The Quest for Welfare-Friendly Feeding of Broiler Breeders: Effects of Daily vs.
      5:2 Feed Restriction Schedules.
AB  - Restricted feeding of broiler breeders is required for improved long-term health
      and welfare. Because feeding frustration and hunger are major welfare concerns
      during rearing, many suggestions have been made to decrease the negative feelings
      of hunger while maintaining suitable growth rates and reproductive health. Non
      daily ("skip-a-day") feeding schedules are commonly used around the world to
      increase portion sizes at meal times while restricting intake but these practices
      are prohibited in many countries due to welfare concerns on fasting days. We
      compared birds raised on a non-daily feeding schedule (2 non-consecutive fasting
      days per week, 5:2), previously suggested as a welfare-friendlier non-daily
      alternative, to birds raised on daily feed restriction. We found signs of
      increased physiological stress levels in 5:2 birds, including elevated heterophil
      to lymphocyte ratios (1.00 for 5:2 vs. 0.75 for daily fed at 12 weeks of age),
      increased adiposity (0.21% lean body weight [LBW] for 5:2 vs. 0.13% LBW for daily
      fed), and reduced muscle growth (pectoral muscle 5.94% LBW for 5:2 vs. 6.52% LBW
      for daily fed). At the same time, 5:2 birds showed signs of lower anxiety before
      feeding times (activity was reduced from 10.30 in daily fed to 4.85) which may be
      a result of the lower feed competition associated with larger portion sizes.
      Although we found no difference in latency to first head movement in tonic
      immobility between the treatments (136.5 s on average for both groups), 5:2 birds
      generally showed more interest in a novel object in the home pen which indicated
      increased risk taking and reduced fear while fasting. The 5:2 birds in this study
      showed no signs of learning the feeding schedule, and this unpredictability may
      also increase stress. Taken together, the effects of 5:2 vs. daily feed
      restriction on the welfare of broiler breeder pullets remain inconclusive and
      differ between feeding and fasting days. In addition to reducing stress by
      minimizing the number of fasting days, we suggest that a shift to more
      predictable schedules may help improve the welfare of broiler breeder pullets.

PMID- 29182753
TI  - Isolated cardiac sarcoidosis: the crucial role of multimodal imaging with
      positron emission tomography/magnetic resonance imaging in diagnosis and therapy
      surveillance.

PMID- 29182754
TI  - Pharmacogenetics-Based Warfarin Dosing in Patients With Cardiac Valve
      Replacement: The Effects of CYP2C9 and VKORC1 Gene Polymorphisms.
AB  - Many lines of evidence suggest that warfarin dosing variability is significantly
      associated with cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase
      complex subunit 1 (VKORC1) variant alleles. Therefore, we investigated the
      influence of CYP2C9*2 (430C/T), *3 (1075A/C) and VKORC1 (-1639G/A) polymorphisms
      on warfarin dose requirements in patients who underwent cardiac valve surgery
      during the postoperative period.A total of 100 patients with heart valve
      replacement who had a prescribed target international normalized ratio (INR)
      range of 2-3 were enrolled in the study. Genotyping of CYP2C9 and VKORC1 was
      carried out using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) technique. The demographic and clinical data were
      collected using a precodified questionnaire and clinical examination and then
      were analyzed.Our findings revealed that the prevalence of CYP2C9 *2, *3 and
      VKORC1 -1639A alleles in patients were 10.5%, 39%, and 48%, respectively. We also
      found that patients with CYP2C9 *1 and VKORC1 -1639G alleles required the highest
      dosages of warfarin, while the carriers of CYP2C9 variant *2 and *3 alleles and
      VKORC1 -1639A required less warfarin. Univariate regression analysis showed that
      age and presence of CYP2C9 *2 allele significantly influenced the daily warfarin
      dose requirement. Our findings provide additional evidence to support the
      hypothesis that CYP2C9*2 (430C/T), *3 (1075A/C) and VKORC1 (-1639G/A)
      polymorphisms explain a considerable proportion of interindividual variability in
      warfarin dose. Therefore, testing for these variants might be helpful for
      adjusting patient warfarin dosage to an effective and safe level.

PMID- 29182756
TI  - Acute phase proteins and stress markers in the immediate response to a combined
      vaccination against Newcastle disease and infectious bronchitis viruses in
      specific pathogen free (SPF) layer chicks.
AB  - Vaccination is an important tool in poultry health, but is itself a stressor
      often resulting in a reduction in feed intake, body weight gain, and nutrient
      digestibility. In other species, vaccination is associated with an immediate
      acute-phase response. As an important immune parameter, the circulating
      heterophil/lymphocyte (H/L) ratio is a well-recognized parameter of stress in
      poultry. In this study, the effects of a routinely used commercial poultry
      vaccine on the acute phase response (APR) and H/L ratios in specific pathogen
      free (SPF) layer chicks was examined to determine if post vaccination (PV) stress
      and an APR occur. A combined Newcastle disease and infectious bronchitis vaccine
      (Nobalis Ma5+Clone 30) was administered to SPF chicks by the intraocular route at
      age 7 d. Acute phase proteins (APP), alpha-1 acid glycoprotein (AGP) and serum
      amyloid A (SAA) were measured by enzyme-linked immunosorbent assays at d 0 (pre
      vaccination) and d 0.5, 1, 2, 3, 4, 5, 6, and 21 PV. Stress was determined in the
      chicks by measurement of the H/L ratio. The immune response to the vaccine was
      estimated by measurement of the antibody (IgY) response to the vaccine at d
      21.The antibody titer was significantly (P < 0.05) higher in the vaccinated group
      at 21 d PV, confirming stimulation of the immune system. The H/L ratio was also
      significantly higher in the vaccinated group at 1 to 2 d (P < 0.01) and at 3 d (P
      < 0.05) PV. The concentration of SAA increased by 2.8-fold, from 63.7 MUg/mL in
      controls to 181 MUg/mL in the vaccinated group, (P < 0.05) at 1 d PV. AGP
      increased 1.6-fold at 2 d PV, (from 0.75 g/mL in the control group to 1.24 g/mL
      in the vaccinated group, P < 0.05).In conclusion an immediate but mild APR
      occurred in the chicks following intraocular vaccination, whereas the stress
      response as measured by H/L ratio seemed to be more specific and sensitive.
      Measurement of these biomarkers of the host response could be a tool in vaccine
      development.

PMID- 29182757
TI  - Super-response to cardiac resynchronization therapy may predict late phrenic
      nerve stimulation.
AB  - Aims : Changes in the anatomical relationship between left phrenic nerve and
      coronary veins may occur due to the reverse remodelling observed in super
      responders to cardiac resynchronization therapy (CRT) and might be the underlying
      mechanism in patients developing late-onset phrenic nerve stimulation (PNS)
      without evidence of lead dislodgement (LD). In this study, we sought to evaluate
      the role of super-response (SR) to CRT as a potential predictor of late-onset
      PNS. Methods and results: Consecutive patients implanted with a left ventricular
      (LV) lead in a single centre were retrospectively analysed. Phrenic nerve
      stimulation was classified as 'early' when it occurred within 3 months of
      implantation and 'late' for occurrences thereafter. 'Late' PNS was considered
      related to LD (LD-PNS) when LV threshold differed by > 1 V or impedance >250
      Omega from baseline values or in case of radiological displacement. Cases not
      meeting the former criteria were classified as 'non-LD-PNS'. Super-response was
      defined as a decrease >=30% of the left ventricluar end-systolic volume at 1-year
      echocardiography. At 32 +/- 7 months follow-up, PNS occurred in 20 of 139
      patients. Late non-LD-PNS incidence was significantly higher in the SR group
      (8/61; 13.1%) when compared with the non-SR (1/78; 1.3%) (P = 0.010). Super
      response remained the only predictor of non-LD-PNS at multivariate analysis (odds
      ratio: 11.62, 95% confidence interval 1.41-95.68, P = 0.023). Conclusion:
      Incidence of late non-LD-PNS is higher among SR to CRT, suggesting a potential
      role of the changes in the anatomical relationship between left phrenic nerve and
      coronary veins.

PMID- 29182755
TI  - Meta-analysis of DNA double-strand break response kinetics.
AB  - Most proteins involved in the DNA double-strand break response (DSBR) accumulate
      at the damage sites, where they perform functions related to damage signaling,
      chromatin remodeling and repair. Over the last two decades, studying the
      accumulation of many DSBR proteins provided information about their functionality
      and underlying mechanisms of action. However, comparison and systemic
      interpretation of these data is challenging due to their scattered nature and
      differing experimental approaches. Here, we extracted, analyzed and compared the
      available results describing accumulation of 79 DSBR proteins at sites of DNA
      damage, which can be further explored using Cumulus (http://www.dna
      repair.live/cumulus/)-the accompanying interactive online application. Despite
      large inter-study variability, our analysis revealed that the accumulation of
      most proteins starts immediately after damage induction, occurs in parallel and
      peaks within 15-20 min. Various DSBR pathways are characterized by distinct
      accumulation kinetics with major non-homologous end joining proteins being
      generally faster than those involved in homologous recombination, and signaling
      and chromatin remodeling factors accumulating with varying speeds. Our meta
      analysis provides, for the first time, comprehensive overview of the temporal
      organization of the DSBR in mammalian cells and could serve as a reference for
      future mechanistic studies of this complex process.

PMID- 29182758
TI  - MicroRNA-122 targets genes related to goose fatty liver.
AB  - MicroRNA-122 (miR-122), a completely conserved, liver-specific miRNA in
      vertebrates, is essential for the maintenance of liver homeostasis. This 22
      nucleotide-length RNA regulates diverse functions such as cholesterol, glucose,
      and lipid metabolism as well as iron homeostasis and infection of hepatitis C
      virus (HCV). Landes goose, which has a good, fatty liver, has important
      significance for us in studying miR-122 function in goose fatty liver. In the
      current study, we identified miR-122 in goose liver and its expression pattern
      and target genes. We found that miR-122 was highly expressed in goose liver and
      its expression was down-regulated after overfeeding; some genes related to lipid
      metabolism, including prolyl 4-hydroxylase subunit alpha 1 (P4HA1); aldolase,
      fructose-bisphosphate B (ALDOB); and pyruvate kinase, muscle (PKM2), were
      predicted and validated as target genes of goose miR-122. After overexpression or
      inhibition of miR-122 in primary goose hepatocytes, the expression of ALDOB and
      PKM2 was changed, but not that of P4HA1, indicating miR-122 regulates ALDOB and
      PKM2 expression at the mRNA level. These findings suggest miR-122 play important
      roles in goose fatty liver by targeting some of the genes related to lipid
      metabolism.

PMID- 29182759
TI  - Long-term outcome after anomalous left coronary artery from the pulmonary artery
      repair: a 40-year single-centre experience.
AB  - OBJECTIVES: An anomalous left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital anomaly, often associated with severely impaired left
      ventricular (LV) contractility and functional mitral valve (MV) regurgitation.
      Current data suggest that earlier correction of ALCAPA may result in a more
      complete recovery of LV function. By analysing the results of a large single
      centre ALCAPA cohort, we sought to investigate whether these treatment paradigms
      remain valid. METHODS: A retrospective study was performed evaluating all
      patients undergoing repair of ALCAPA over a period of almost 40 years. All
      preoperative and postoperative echocardiographic reports were reviewed, focusing
      on the recovery of LV and MV function. RESULTS: The study cohort included 78
      patients who underwent ALCAPA repair between 1977 and 2015, who were divided into
      2 groups based on patient age at initial repair: Group A (n = 52, age <1 year)
      and Group B (n = 26, age >1 year). Following repair, systolic LV and MV function
      improved significantly (P < 0.01) in both groups. Patient age at the time of
      initial surgery had no significant influence on the improvement of LV function.
      Early mortality (within 30 days) was 10% (n = 8). No 30-day mortality was
      reported in the past 20 years. Survival at 20 years following ALCAPA repair was
      86 +/- 4%. CONCLUSIONS: Following ALCAPA repair, LV function significantly
      improved, regardless of age at the time of repair. In addition, preoperative
      functional MV regurgitation decreased over time. Concomitant mitral valve surgery
      at the time of ALCAPA repair is required in patients with structural
      abnormalities of the MV.

PMID- 29182760
TI  - Expression Patterns of TNFalpha, MAdCAM1, and STAT3 in Intestinal and Skin
      Manifestations of Inflammatory Bowel Disease.
AB  - Background: Pathogenesis of cutaneous extraintestinal manifestations [EIM] in
      inflammatory bowel disease [IBD] remains elusive. Efficacy of anti-TNF agents
      suggests TNF-dependent mechanisms. The role of other biologics, such as anti
      integrins or JAK-inhibitors, is not yet clear. Methods: We performed
      immunohistochemistry for TNFalpha, NFkappaB, STAT1/STAT3, MAdCAM1, CD20/68,
      caspase 3/9, IFNgamma, and Hsp-27/70 on 240 intestinal [55 controls, 185 IBD] and
      64 skin biopsies [11 controls, 18 erythema nodosum [EN], 13 pyoderma gangenosum
      [PG], 22 psoriasis]. A semiquantitative score [0-100%] was used for evaluation.
      Results: TNFalpha was upregulated in intestinal biopsies from active Crohn's
      disease [CD] vs controls [36.2 vs 12.1, p < 0.001], but not ulcerative colitis
      [UC: 17.9]. NFkappaB, however, was upregulated in intestinal biopsies from both
      active CD and UC [43.2 and 34.5 vs 21.8, p < 0.001 and p = 0.017, respectively].
      TNFalpha and NFkappaB were overexpressed in skin biopsies from EN, PG, and
      psoriasis. No MAdCAM1 overexpression was seen in skin tissues, whereas it was
      upregulated in active UC vs controls [57.5 vs 35.4, p = 0.003]. STAT3 was
      overexpressed in the intestinal mucosa of active and non-active IBD, and a
      similar upregulation was seen in skin biopsies from EN [84.7 vs 22.3, p < 0.001]
      and PG [60.5 vs 22.3, p = 0.011], but not in psoriasis. Caspase 3 and CD68
      overexpression in skin biopsies distinguished EN/PG from psoriasis and controls.
      Conclusions: Upregulation of TNFalpha/NFkappaB in EN and PG is compatible with
      the efficacy of anti-TNF in EIM management. Data on overexpressed STAT3, but not
      MAdCAM1, support a rationale for JAK-inhibitors in EN and PG, while questioning
      the role of vedolizumab.

PMID- 29182761
TI  - Sugar and Aldehyde Content in Flavored Electronic Cigarette Liquids.
AB  - Introduction: Sugars are major constituents and additives in traditional tobacco
      products, but little is known about their content or related toxins
      (formaldehyde, acetaldehyde, and acrolein) in electronic cigarette (e-cigarette)
      liquids. This study quantified levels of sugars and aldehydes in e-cigarette
      liquids across brands, flavors, and nicotine concentrations (n = 66). Methods:
      Unheated e-cigarette liquids were analyzed using liquid chromatography mass
      spectrometry and enzymatic test kits. Generalized linear models, Fisher's exact
      test, and Pearson's correlation coefficient assessed sugar, aldehyde, and
      nicotine concentration associations. Results: Glucose, fructose and sucrose
      levels exceeded the limits of quantification in 22%, 53% and 53% of the samples.
      Sucrose levels were significantly higher than glucose [chi2(1) = 85.9, p < .0001]
      and fructose [chi2(1) = 10.6, p = .001] levels. Formaldehyde, acetaldehyde, and
      acrolein levels exceeded the limits of quantification in 72%, 84%, and 75% of the
      samples. Acetaldehyde levels were significantly higher than formaldehyde [chi2(1)
      = 11.7, p = .0006] and acrolein [chi2(1) = 119.5, p < .0001] levels. Differences
      between nicotine-based and zero-nicotine labeled e-cigarette liquids were not
      statistically significant for sugars or aldehydes. We found significant
      correlations between formaldehyde and fructose (-0.22, p = .004) and sucrose (
      0.25, p = .002) and acrolein and fructose (-0.26, p = .0006) and sucrose (-0.21,
      p = .0006). There were no significant correlations between acetaldehyde and any
      of the sugars or any of the aldehydes and glucose. Conclusions: Sugars and
      related aldehydes were identified in unheated e-cigarette liquids and their
      composition may influence experimentation in naive users and their potential
      toxicity. Implications: The data can inform the regulation of specific flavor
      constituents in tobacco products as a strategy to protect young people from using
      e-cigarettes, while balancing FDA's interest in how these emerging products could
      potentially benefit adult smokers who are seeking to safely quit cigarette
      smoking. The data can also be used to educate consumers about ingredients in
      products that may contain nicotine and inform future FDA regulatory policies
      related to product standards and accurate and comprehensible labeling of e
      cigarette liquids.

PMID- 29182762
TI  - Cognitive Function Among Antiretroviral Treatment-Naive Individuals Infected With
      Human Immunodeficiency Virus Type 1 Subtype G Versus CRF02_AG in Nigeria.
AB  - Background: Human immunodeficiency virus type 1 (HIV-1) subtype has been shown to
      be associated with disease progression. We compared cognitive function between
      individuals infected with HIV-1 subtype G and CRF02_AG in Nigeria. Methods: For
      this cross-sectional study, samples were analyzed from 146 antiretroviral-naive
      participants. Genotypic analysis of plasma HIV RNA was performed by nested
      polymerase chain reaction of protease and reverse transcriptase genes, and
      sequences were aligned with curated HIV-1 subtype references. Cognitive status
      was determined using demographically adjusted T scores and global deficit score
      (GDS) obtained from a comprehensive neuropsychological test battery. Results: A
      total of 76 (52.1%) participants were infected with CRF02_AG, 48 (32.8%) with
      subtype G, and 22 (15.1%) with other HIV-1 strains. In a multivariable linear
      regression adjusting for plasma HIV RNA, CD4 count, and depression score, mean
      global T score was lower among subtype G-infected compared with CRF02_AG-infected
      participants (mean difference, -3.0 [95% confidence interval {CI}, -5.2, to -.7];
      P = .011). Also, T scores were significantly lower among subtype G- than CRF02_AG
      infected participants for the speed of information processing, executive
      function, and verbal fluency ability domains. Adjusting for similar variables in
      a logistic regression, the odds of global cognitive impairment (GDS >=0.5) were
      2.2 times higher among subtype G compared with CRF02_AG-infected participants
      (odds ratio, 2.2 [95% CI, .9-5.4]; P = .078). Conclusions: Cognitive performance
      was significantly worse among antiretroviral-naive individuals with HIV-1 subtype
      G vs CRF02_AG infection. Further studies are required to characterize the
      mechanistic basis for these differences.

PMID- 29182763
TI  - Salvage radiotherapy for second oligo-recurrence in patients with breast cancer.
AB  - A new concept designated 'oligo-recurrence (OR)' has been proposed, which
      indicates one to several distant metastases/recurrences in one or more organs,
      which can be treated with local therapy, after the primary site of the cancer has
      been controlled. The purpose of this study was to assess the efficacy and
      toxicity of salvage radiotherapy (RT) for the second OR of breast cancer. The
      second OR was defined as once-salvaged patients with OR who had a second failure
      that was also detected as the state of OR. Twenty-one patients with second OR
      were treated with salvage RT and were retrospectively analyzed. The sites of the
      second OR were locoregional recurrence in 7 patients and distant metastasis in 14
      patients. Salvage RT was performed at a median total dose of 60 Gy. Nineteen
      (90%) patients had an objective response. The median overall survival and
      progression-free survival (PFS) times were 41 and 24 months after salvage RT for
      the second OR, respectively. The 3-year local (in-field) control (LC) rates were
      93%. The toxicities were mild; acute toxicities >=Grade 3 were seen in one
      patient with Grade 3 dermatitis, and no late toxicity >=Grade 2 was observed. In
      conclusion, salvage RT for the second OR was able to achieve a better LC rate and
      longer PFS time without inducing severe toxicity, and therefore may be a
      potentially effective modality for inducing long-term survival in select
      patients.

PMID- 29182764
TI  - Balloon-expandable transapical transcatheter aortic valve implantation with or
      without predilation of the aortic valve: results of a multicentre registry.
AB  - OBJECTIVES: To assess safety and efficacy of transapical transcatheter aortic
      valve implantation (TA-TAVI) in the absence of predilation using balloon aortic
      valvuloplasty (BAV). Predilation of the stenosed valve using BAV is a routine
      step in TA-TAVI; however, evidence supporting its clinical value is lacking, and
      several studies have linked it with higher complication rates. METHODS: A
      prospective, two-armed, multicentre registry (EASE-IT TA) to gather data on
      patients undergoing TA-TAVI with or without BAV, using the Edwards SAPIEN 3 valve
      was designed. The primary evaluation criterion was a composite of all-cause
      mortality, non-fatal stroke, non-fatal myocardial infarction, acute kidney injury
      and pacemaker implantation [per Valve Academic Research Consortium-2 (VARC-2)]
      within 30 days after TAVI. RESULTS: A total of 198 subjects underwent TA-TAVI, 61
      with and 137 without BAV. Patient characteristics were comparable at baseline
      (mean +/- SD: age 80.3 +/- 5.7 years; logistic EuroSCORE 20.2 +/- 12.6). Similar
      reductions in peak and mean transvalvular gradients were observed post
      procedurally. There was a significant reduction of fluoroscopy time without BAV
      (4.7 vs 7.9 min; P = 0.039) and significantly decreased odds of catecholamine
      administration (17.5% vs 32.8%; P = 0.017). A decreased odds of the primary
      evaluation criterion in patients without BAV after 30 days (adjusted odds ratio
      0.71; 95% confidence interval 0.34-1.82) and the same composite end-point after 6
      months (adjusted odds ratio 0.74; 95% confidence interval 0.37-1.47) were not
      significant even after multivariable adjustment. CONCLUSIONS: TA-TAVI without BAV
      appears to be at least equal to its conventional counterpart in terms of efficacy
      and may offer advantages in terms of safety. Thus, there appears to be little
      justification for maintaining the BAV step in TA-TAVI for many patients.

PMID- 29182765
TI  - qPCR-25 years old but still a matter of debate.

PMID- 29182766
TI  - Neuronal ceroid lipofuscinosis with severe biventricular impairment: a rare
      genetic disorder with associated myopathy?

PMID- 29182767
TI  - Letter: Spontaneous Third Ventriculostomy in a Patient Following Traumatic Brain
      Injury.

PMID- 29182768
TI  - Obesity-induced vascular dysfunction and arterial stiffening requires endothelial
      cell arginase 1.

PMID- 29182769
TI  - The Quality of Nonprey Food Affects Cannibalism, Intraguild Predation, and
      Hyperpredation in Two Species of Phytoseiid Mites.
AB  - Generalist arthropod predators not only prey on herbivores but also may engage in
      competitive interactions by attacking and consuming conspecifics (cannibalism) or
      other predators (intraguild predation [IGP] and hyperpredation). These types of
      interactions are quite common among predators used in biological control.
      Although there is evidence that nonprey food relaxes cannibalism and IGP, there
      is little information regarding the impact of the quality of the nonprey food.
      Herein, we examined how pollen of different nutritional quality (pine, narrow
      leaf cattail, or apple) impacted 1) the cannibalism by females of Euseius
      stipulatus (Athias-Henriot) (Acari: Phytoseiidae) on conspecific larvae, 2) the
      reciprocal predation between gravid females of E. stipulatus or Iphiseius
      degenerans (Berlese) (Acari: Phytoseiidae) and heterospecific larvae, and 3) the
      predation of E. stipulatus on the eggs of the aphid predator Aphidoletes
      aphidimyza (Rondani) (Diptera: Cecidomyiidae). E. stipulatus cannibalism was
      significantly reduced in the cattail pollen treatment, whereas in the pine pollen
      it did not significantly differ from control (no food). Predation between I.
      degenerans and E. stipulatus was significantly reduced in the cattail pollen
      treatment as compared to the control treatment. Finally, predation of E.
      stipulatus on A. aphidimyza eggs was significantly reduced when cattail or apple
      pollen was provided compared to the pine pollen or control treatments. These
      results suggest that cattail or apple pollen is suitable for mitigating negative
      interactions among generalist predatory mites used in biological control.

PMID- 29182770
TI  - Field Distribution and Density of Culicoides sonorensis (Diptera:
      Ceratopogonidae) Eggs in Dairy Wastewater Habitats.
AB  - Culicoides sonorensis Wirth and Jones (Diptera: Ceratopogonidae) is a key
      bluetongue virus vector in the United States. Immatures occur in mud near the
      edges of wastewater ponds and are understudied targets for control efforts. Eggs
      of C. sonorensis were collected in the morning from a dairy wastewater pond bank
      by taking 5-ml surface mud samples along four transects on each of six dates.
      Surface mud samples parallel to waterline (10-cm long, 1-cm wide, and 0.5-cm
      deep) were removed at 5-cm increments ranging from 15 cm below waterline up to 25
      cm above waterline. Eggs were removed using MgSO4 flotation, held on moist filter
      paper, and scored for hatching over 3 d. Eggs hatching on days 2 and 3 were
      assumed to have been laid on the test night. Water levels were stable within a
      night according to time-lapse camera photos. Most samples from below the
      waterline had no eggs and were not analyzed statistically. Mean (+/-SE) sample
      moisture (25.8 +/- 2.1 at 5 cm above waterline and 19.8 +/- 2.6% at 25 cm above
      waterline) did not vary significantly by position above waterline. The highest
      density of viable eggs (21 eggs/5 ml), proportion of mud samples positive for
      viable eggs (75%), and proportion of eggs hatching (80%) were found 5 cm above
      waterline. Oviposition in the few hours after sunset is adaptive, allowing eggs
      to age, develop the serosal cuticle, and resist later desiccation. As a potential
      control method, reducing water levels after midnight would encourage young egg
      desiccation.

PMID- 29182771
TI  - Limited Evidence for the Need for Region-Specific, Genotypic Drug-Susceptibility
      Assays for Mycobacterium tuberculosis.

PMID- 29182772
TI  - Identification of Ceratitis capitata (Diptera: Tephritidae) Sperm From Females in
      Traps: The Importance of the Ventral Receptacle.
AB  - The monitoring of a pest population often relies on the identification of
      individuals from traps. For area-wide programs utilizing the sterile insect
      technique, the further identification of the mated status of females found in
      traps is of utmost importance. For the Mediterranean fruit fly, Ceratitis
      capitata (Wiedemann) (Diptera: Tephritidae), this is usually verified through the
      assessment of sperm in the spermathecae. However, this can be misleading for
      species where there are other sperm storage organs such as the ventral
      receptacle. Here, we studied the relative importance of sperm storage in the
      ventral receptacle compared to the spermathecae for females from 5 to 18 d of
      age. Furthermore, we studied how sperm can be identified in the ventral
      receptacle or spermathecae after females were recovered from traps. We found no
      effect of female age on likelihood of sperm storage. Sperm could be identified in
      both sperm storage organs at 7 or 14 d after females had been placed in traps. We
      found that the ventral receptacle is a more reliable indicator of female mated
      status. Thus, we propose that if no sperm are found in the spermathecae, program
      managers should revise the ventral receptacle before assuming that females are
      not mated. This test may also be relevant to other pest tephritids that store
      even more sperm in the ventral receptacle than C. capitata.

PMID- 29182773
TI  - Mechanism of formation of a toroid around DNA by the mismatch sensor protein.
AB  - The DNA mismatch repair (MMR) pathway removes errors that appear during genome
      replication. MutS is the primary mismatch sensor and forms an asymmetric dimer
      that encircles DNA to bend it to scan for mismatches. The mechanism utilized to
      load DNA into the central tunnel was unknown and the origin of the force required
      to bend DNA was unclear. We show that, in absence of DNA, MutS forms a symmetric
      dimer wherein a gap exists between the monomers through which DNA can enter the
      central tunnel. The comparison with structures of MutS-DNA complexes suggests
      that the mismatch scanning monomer (Bm) will move by nearly 50 A to associate
      with the other monomer (Am). Consequently, the N-terminal domains of both
      monomers will press onto DNA to bend it. The proposed mechanism of toroid
      formation evinces that the force required to bend DNA arises primarily due to the
      movement of Bm and hence, the MutS dimer acts like a pair of pliers to bend DNA.
      We also shed light on the allosteric mechanism that influences the expulsion of
      adenosine triphosphate from Am on DNA binding. Overall, this study provides
      mechanistic insight regarding the primary event in MMR i.e. the assembly of the
      MutS-DNA complex.

PMID- 29182775
TI  - Transcriptional profile of the human skin pathogenic fungus Mucor irregularis in
      response to low oxygen.

PMID- 29182774
TI  - Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the
      m.1555A>G mtDNA variant in a large multigenerational family.
AB  - The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons
      for the highly variable clinical penetrance are not known. Exome sequencing
      identified a heterozygous start loss mutation in SSBP1, encoding the single
      stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi
      generational family transmitting m.1555A>G, associated with mtDNA depletion and
      multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state
      SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding
      the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific
      manner. This family demonstrates the importance of rare trans-acting genetic
      nuclear modifiers in the clinical expression of mtDNA disease.

PMID- 29182776
TI  - Crystal structure of an anti-CRISPR protein, AcrIIA1.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR
      associated (Cas) proteins provide bacteria with RNA-based adaptive immunity
      against phage infection. To counteract this defense mechanism, phages evolved
      anti-CRISPR (Acr) proteins that inactivate the CRISPR-Cas systems. AcrIIA1,
      encoded by Listeria monocytogenes prophages, is the most prevalent among the Acr
      proteins targeting type II-A CRISPR-Cas systems and has been used as a marker to
      identify other Acr proteins. Here, we report the crystal structure of AcrIIA1 and
      its RNA-binding affinity. AcrIIA1 forms a dimer with a novel two helical-domain
      architecture. The N-terminal domain of AcrIIA1 exhibits a helix-turn-helix motif
      similar to transcriptional factors. When overexpressed in Escherichia coli,
      AcrIIA1 associates with RNAs, suggesting that AcrIIA1 functions via nucleic acid
      recognition. Taken together, the unique structural and functional features of
      AcrIIA1 suggest its distinct mode of Acr activity, expanding the diversity of the
      inhibitory mechanisms employed by Acr proteins.

PMID- 29182777
TI  - Evaluation of a prognostic scoring system based on the systemic inflammatory and
      nutritional status of patients with locally advanced non-small-cell lung cancer
      treated with chemoradiotherapy.
AB  - Systemic inflammation and poor nutritional status have a negative effect on the
      outcomes of cancer. Here, we analyzed the effects of the pretreatment
      inflammatory and nutritional status on clinical outcomes of locally advanced non
      small-cell lung cancer (NSCLC) patients treated with chemoradiotherapy. We
      retrospectively reviewed 89 patients with locally advanced NSCLC treated with
      chemoradiotherapy between July 2006 and June 2013. Serum C-reactive protein (CRP)
      was assessed as an inflammatory marker, and serum albumin, body mass index (BMI)
      and skeletal mass index were assessed as nutritional status markers. The
      relationships between these markers and overall survival (OS) were assessed. The
      median OS was 24.6 months [95% confidence interval (CI): 19.4-39.3 months].
      During follow-up, 58 patients (65%) had disease recurrence and 52 patients (58%)
      died. In multivariate Cox hazard analysis, CRP levels and BMI approached but did
      not achieve a significant association with OS (P = 0.062 and 0.094,
      respectively). Recursive partitioning analysis identified three prognostic groups
      based on hazard similarity (CRP-BMI scores): 0 = CRP < 0.3 mg/dl, 1 = CRP >= 0.3
      mg/dl and BMI >= 18.5 kg/m2, and 2 = CRP >= 0.3 mg/dl and BMI < 18.5 kg/m2. The
      CRP-BMI score was significantly associated with OS (P = 0.023). Patients with
      scores of 0, 1 and 2 had median OS of 39.3, 24.5 and 14.5 months, respectively,
      and the scores also predicted the probability of receiving salvage treatment
      after recurrence. The CRP-BMI score is thus a simple and useful prognostic marker
      of clinical outcome for patients with locally advanced NSCLC treated with
      chemoradiotherapy.

PMID- 29182778
TI  - Jointly aligning a group of DNA reads improves accuracy of identifying large
      deletions.
AB  - Performing sequence alignment to identify structural variants, such as large
      deletions, from genome sequencing data is a fundamental task, but current methods
      are far from perfect. The current practice is to independently align each DNA
      read to a reference genome. We show that the propensity of genomic rearrangements
      to accumulate in repeat-rich regions imposes severe ambiguities in these
      alignments, and consequently on the variant calls-with current read lengths, this
      affects more than one third of known large deletions in the C. Venter genome. We
      present a method to jointly align reads to a genome, whereby alignment ambiguity
      of one read can be disambiguated by other reads. We show this leads to a
      significant improvement in the accuracy of identifying large deletions (>=20
      bases), while imposing minimal computational overhead and maintaining an overall
      running time that is at par with current tools. A software implementation is
      available as an open-source Python program called JRA at
      https://bitbucket.org/jointreadalignment/jra-src.

PMID- 29182779
TI  - Phosphine Resistance in North American Field Populations of the Lesser Grain
      Borer, Rhyzopertha dominica (Coleoptera: Bostrichidae).
AB  - Phosphine is the most widely used fumigant for stored grain insect pests, and
      resistance to phosphine has evolved in several species worldwide. This study was
      designed to determine the presence of phosphine resistance in 34 populations of
      Rhyzopertha dominica (F.) collected from the United States and Canada. Adult R.
      dominica were sampled and subjected to a discriminatory dose toxicity assay of
      exposure to 20 ppm of phosphine for 20 h of exposure to distinguish a susceptible
      R. dominica adult by death from a resistant beetle that survives the treatment.
      All but two of the 34 geographic populations surveyed had some beetles that were
      resistant to phosphine, and the frequency of resistance varied from 97% in a
      population from Parlier, California to 0% in beetles from both Carnduff,
      Saskatchewan and Starbuck, Manitoba. Probit analyses of dose-mortality bioassays
      with beetles from a laboratory-susceptible strain and those from five of the
      populations sampled were used to calculate resistance ratio factors (RRs) based
      on the ratio of LC50 (estimate for the concentration to kill 50% of a test group)
      in the sampled population to the LC50 for the susceptible strain. The highest RR
      for the five resistant populations was nearly 596-fold in beetles from Belle
      Glade, Florida, whereas the lowest RR in that group was 9-fold in Wamego, Kansas.
      This study revealed that phosphine resistance in R. dominica is common across
      North America and some populations have levels of resistance that may pose
      challenges for continued use of phosphine for their management.

PMID- 29182780
TI  - Cold Hardiness of Overwintering Larvae of Sphenoptera sp. (Coleoptera:
      Buprestidae) in Western China.
AB  - An undetermined species of Sphenoptera sp. is an important pest of Artemisia
      ordosica Krasch, and recently, an outbreak of this insect has spread throughout
      Ningxia, Inner Mongolia, Shanxi, and other regions in western China. The cold
      hardiness of overwintering larvae of Sphenoptera sp. was determined by measuring
      their supercooling point (SCP) and their mortality at sub-zero temperatures.
      Additionally, quantitative changes in sugars and low molecular weight sugar
      alcohols in larvae were determined following exposure of larvae to low
      temperatures. Mean SCP of overwintering larvae (i.e., collected in January) was 
      30.2 +/- 0.60 degrees C. The mortality rate of larvae approached 100% at -30
      degrees C, whereas mortality rates of larvae in the higher temperature treatments
      were generally less than 25%. Five sugars and sugar alcohols (i.e., glycerol,
      fructose, glucose, inositol, and trehalose) were detected in larvae. When larvae
      were exposed to low temperatures for 4 h, inositol, trehalose and total content
      was generally higher at the highest incubation temperature (-10 degrees C) than
      at lower incubation temperatures. Following a longer exposure (30 d), content of
      fructose, glucose, trehalose and total content generally increased with
      decreasing temperature down to -25 degrees C. Thus it appears that Sphenoptera
      sp. larvae are freeze avoidant, and their cold hardiness may be achieved by
      accumulation low molecular weight sugars and sugar alcohols.

PMID- 29182782
TI  - Abundance and Dynamics of Anopheles (Diptera: Culicidae) Larvae in a Malaria
      Endemic Area of Bangladesh.
AB  - Malaria is a major health burden in the border-belt areas of Bangladesh. There
      are recent data from adult mosquito collections that a number of vectors are
      involved in the transmission cycle. However, little information regarding the
      larval habitats of Anopheles mosquitoes are available in Bangladesh. To start
      filling this gap, a cross-sectional larval survey was conducted in Bandarban,
      Bangladesh from October 2011 to September 2012. Descriptive analysis, Poisson
      regression, spearman correlations and zero-inflated Poisson regression were used
      to calculate the degree of association between the abundance of larval Anopheles
      species and environmental factors. From the 300 larval habitats sampled, 5,568
      Anopheles larvae were collected and of these, 2,263 (40.6%) were identified to
      species. Collections represented 16 Anopheles species with Anopheles vagus
      (26.4%, n = 598) as the dominant species. A total of 16 Anopheles larval habitat
      types were identified. Larval abundance was significantly different (P < 0.05)
      among habitats with pond (40%, n = 914) and rice field (34%, n = 779) implicated
      to be the most utilized. Larval abundance varied significantly (P < 0.05) with
      habitat characteristics. Most of the larvae were collected from sites with a
      range of pH from 7.0 to 8.0. Data obtained from this study revealed both natural
      and human-created larval habitats were favorable for anopheline larval survival
      and development. Such information elucidates plausible drivers of high anopheline
      diversity, high vector abundance, changes in relative species abundance from
      historic data, and sustained transmission of malaria in endemic areas of
      Bangladesh.

PMID- 29182781
TI  - Resistance in 27 Rice Cultivars to Sugarcane Borer (Lepidoptera: Crambidae).
AB  - Rice (Oryza sativa L.) is considered one of the most important crops in the
      world, and the sugarcane borer, Diatraea saccharalis Fabricius (Lepidoptera:
      Crambidae), is among the key pests damaging the crop in the Americas. The
      objective of this work was to identify rice genotypes as a source of resistance
      to D. saccharalis. Rice plants were infested in the greenhouse and subsequently
      evaluated for damage, larval weight and survival, and stem size. The cultivars
      'Bonanca', 'Caripuna', 'IR 42', 'Canela de Ferro', 'SWA Norte', 'BR IRGA 409',
      'Pepita', 'Serra Dourada', 'Araguaia', 'Xingu', 'Tangara', and 'Soberana' showed
      antibiosis antixenosis, or both to D. saccharalis. These cultivars may be used as
      donor sources in the breeding program and used directly by Brazilian farmers as a
      component of rice-integrated pest management.

PMID- 29182783
TI  - Persistent smoking rate after coronary revascularization and factors related to
      smoking cessation in Turkey.
AB  - Background: Although smoking is an established risk factor for coronary artery
      disease, smoking cessation efforts, as part of a lifestyle change, have been
      disappointing so far. Therefore, assessing current smoking trends and identifying
      patients who are at risk of smoking continuation is of paramount importance. In
      this study, our aim was to assess current smoking rates after coronary
      revascularization as of 2017, and to define factors that potentially affect
      smoking cessation. Methods: Overall, 350 patients who had undergone coronary
      revascularization, either by percutaneous coronary intervention or bypass surgery
      were included in this cross-sectional, observational study. Patients were queried
      for various sociodemographic characteristics and smoking habits. Disease related
      data were obtained from the hospital archives. Results: The overall smoking rate
      was 57% after coronary revascularization. Age, bypass surgery and the occurrence
      of in-hospital adverse events were found to be independent predictors of smoking
      cessation in multivariate analysis. Conclusions: Despite efforts, smoking rates
      after coronary intervention remain substantially high. Therefore, a
      multidisciplinary approach to smoking cessation that incorporates cardiac
      rehabilitation programs and medications should be implemented in clinical
      practice.

PMID- 29182784
TI  - Redescription of Periglischrus herrerai (Acari: Spinturnicidae) Associated to
      Desmodus rotundus (Chiroptera: Phyllostomidae: Desmodontinae), With a Description
      of Adult Female Heteromorphism and an Analysis of its Variability Throughout the
      Neotropics.
AB  - A redescription, with a discussion of new features and illustrations, for all
      life stages is presented for the parasitic mite Periglischrus herrerai Machado
      Allison associated with the common vampire bat Desmodus rotundus (Geoffoy),
      including a description of the heteromorphic female and the first description of
      its female deutonymph. In addition, the morphological variation of P. herrerai is
      evaluated by morphometric analysis of the adults, concluding that there is an
      evident geographic variation throughout the neotropics. This study was possible
      by using type material of P. herrerai from the Machado-Allison collection, and
      voucher specimens from other collections, and specimens from an extensive
      surveying of hematophagous bats in some localities of the Pacific and Atlantic
      versants, and central Mexico.

PMID- 29182785
TI  - Antibiotic therapy in neonates and impact on gut microbiota and antibiotic
      resistance development: a systematic review.
AB  - Objectives: To systematically review the impact of antibiotic therapy in the
      neonatal period on changes in the gut microbiota and/or antibiotic resistance
      development. Methods: Data sources were PubMed, Embase, Medline and the Cochrane
      Database, supplemented by manual searches of reference lists. Randomized
      controlled trials (RCTs) and observational studies were included if they provided
      data on different categories of antibiotic treatment (yes versus no, long versus
      short duration and/or broad- versus narrow-spectrum regimens) and subsequent
      changes in the gut microbiota and/or antibiotic resistance development. We
      evaluated risk of bias using the Cochrane Handbook, adapted to include
      observational studies. When appropriate, we used the vote-counting method to
      perform semi-quantitative meta-analyses. We applied the Grades of Recommendation,
      Assessment, Development and Evaluation approach to rate the quality of evidence
      (QoE). Study protocol registration: PROSPERO CRD42015026743. Results: We included
      48 studies, comprising 3 RCTs and 45 observational studies. Prolonged antibiotic
      treatment was associated with reduced gut microbial diversity in all three
      studies investigating this outcome (very low QoE). Antibiotic treatment was
      associated with reduced colonization rates of protective commensal anaerobic
      bacteria in four of five studies (very low QoE). However, all three categories of
      antibiotic treatment were associated with an increased risk of antibiotic
      resistance development, in particular MDR in Gram-negative bacteria, and we
      graded the QoE for these outcomes as moderate. Conclusions: We are moderately
      confident that antibiotic treatment leads to antibiotic resistance development in
      neonates and it may also induce potentially disease-promoting gut microbiota
      alterations. Our findings emphasize the need to reduce unnecessary antibiotic
      treatment in neonates.

PMID- 29182787
TI  - Dynamics of phosphorus nutrition, allocation and growth of young beech (Fagus
      sylvatica L.) trees in P-rich and P-poor forest soil.
AB  - To investigate how long-lived forest trees cope with low soil phosphorus (P)
      availabilities, we characterized P nutrition of beech (Fagus sylvatica, L.) in
      soils from P-rich and P-poor beech forests throughout an annual growth cycle.
      Young trees were excavated with intact soil cores in mono-specific beech forests,
      kept under common garden conditions, and used for 33P labeling, analyses of P
      uptake, P content and biomass during five phenological stages (dormancy in
      winter, bud swelling in early spring, mature leaves in early and late summer, and
      senescent leaves in fall). Seasonal allocation patterns showed that young,
      emerging leaves were preferred sinks for P under P-poor conditions, thereby
      keeping foliar P concentrations at levels similar to those of trees grown in P
      rich soil. Phosphorus concentrations in stems and roots of trees from the P-poor
      conditions were lower than those from P-rich conditions. Coarse roots were the
      main P storage tissue, supplying inorganic P to newly formed leaves, originating
      from the inorganic and organic P pools under low and high P conditions,
      respectively. Beech trees in P-poor soil exhibited net biomass increment early in
      the annual growth along with a strong P deficit, which was replenished by
      enhanced uptake in late summer and fall. Trees in P-rich soil grew until late
      summer, and showed a moderate P decline in organic pools and recovery late in
      fall, which coincided with elevated P uptake from soil. Beech in P-poor soil
      produced more biomass per unit of P but at a slower growth rate than those in P
      rich soil, thereby exhibiting similar P-use efficiencies. Temporal decoupling of
      growth and P acquisition in combination with internal P trade-off between storage
      tissues and leaves facilitated flexible acclimation of beech to a wide range of
      soil P availabilities.

PMID- 29182786
TI  - Abscisic acid affects expression of citrus FT homologs upon floral induction by
      low temperature in Satsuma mandarin (Citrus unshiu Marc.).
AB  - After a long juvenile period, citrus trees undergo seasonal flowering cycles.
      Under natural conditions, citrus flowering is regulated mainly by low ambient
      temperatures around 15-20  degrees C and water deficit stress. Recent studies
      have revealed that fluctuations in the expression of citrus homologs of FLOWERING
      LOCUS T (FT, encoding a flowering integrator) are correlated with their presumed
      role as flower-promoting signals. Previous ectopic expression analyses have
      demonstrated the flower-promoting function of citrus FT homologs. In this study,
      we examined whether abscisic acid (ABA) affects the expression of FT homologs and
      the flowering induced by low ambient temperatures. Application of exogenous ABA
      to potted Satsuma mandarin (Citrus unshiu Marc.) trees resulted in transient
      accumulation of citrus FT homolog transcripts. The promoter of one citrus FT
      homolog, CiFT3, was active in transgenic A. thaliana (Arabidopsis thaliana) and
      responded to exogenous and endogenous ABA. CiFT3 is preferentially expressed in
      shoots, and its expression was affected by flower-inductive treatments.
      Endogenous ABA accumulated in mandarin shoots during the floral induction period
      at 15  degrees C and under field conditions. The accumulation of ABA was
      correlated with the accumulation of FT homolog transcripts and flowering
      intensity. It was consistent with changes in the expression of genes related to
      ABA metabolism. The abundance of carotenoid precursors that serve as substrates
      for ABA biosynthesis decreased in leaves during the accumulation of ABA. Our data
      indicate that ABA and carotenoid precursors in leaves influence the flowering of
      mandarin trees induced by low temperature.

PMID- 29182788
TI  - Does winter desiccation account for seasonal increases in supercooling capacity
      of Norway spruce bud primordia?
AB  - Bud primordia of Picea abies (L.) H. Karst. remain ice free at subzero
      temperatures by supercooling. Once ice forms inside the primordium, it is
      immediately injured. Supercooling capacity increases seasonally from ~-5  degrees
      C to as much as -50  degrees C by currently unknown mechanisms. Among other
      prerequisites, dehydration of tissues over the winter months has been considered
      to play a key role in freezing tolerance. In this regard, the water content of
      bud primordia may be crucial, especially in reference to supercooling. In order
      to assess the role of dehydration in supercooling capacity, seasonal changes in
      supercooling capacity and the water potential of bud primordia of Picea abies
      (L.) H. Karst were measured at two sites that differed by 1298 m in elevation,
      after artificial frost hardening and dehardening treatments and after controlled
      bench drying. The extent of supercooling of bud primordia varied from -7  degrees
      C in summer to -24.6  degrees C in winter, a difference of 17.6 -19.3 K. Total
      actual water potential (Psitact) of bud primordia was -2 MPa in summer and
      decreased to a mean of -3.8 MPa in midwinter. The decline involved dehydration,
      and to a lesser extent, osmoregulation. At decreased Psitact values (<3.0 MPa),
      supercooling capacity significantly increased <-19.5  degrees C, however, the
      correlation between actual water potential and supercooling capacity was poor.
      Frost-hardening treatments increased the supercooling capacity of bud primordia (
      0.6 K day-1) and lowered Psitact (-0.2 MPa day-1). Frost-dehardening treatments
      reduced supercooling capacity (+1.1 K day-1), and at the same time, increased
      Psitact (+0.3 MPa day-1). In contrast, artificial drying of bud primordia in the
      range observed seasonally (-2.0 MPa) had no effect on supercooling capacity.
      These results suggest that there is no causal relationship between desiccation
      and the supercooling capacity of bud primordia in P. abies, but rather it
      involves other compounds within the cells of the bud primordium that reduce the
      water potential.

PMID- 29182789
TI  - Incidence of Actinic Keratosis and Risk of Skin Cancer in Subjects with Actinic
      Keratosis: A Population-based Cohort Study.

PMID- 29182790
TI  - Validation of the Itch Severity Item as a Measurement Tool for Pruritus in
      Patients with Psoriasis: Results from a Phase 3 Tofacitinib Program.
AB  - Tofacitinib is an oral Janus kinase inhibitor. This post-hoc analysis aimed to
      investigate the psychometric properties of the Itch Severity Item (ISI), a
      numeric rating scale from 0 (no itching) to 10 (worst possible itching) for
      pruritus in psoriasis, and review the effect of tofacitinib on pruritus in
      patients with psoriasis participating in Phase 3 studies (N = 3,641). The ISI
      showed high test-retest reliability (intra-class correlation coefficient: 0.84).
      The clinically important difference was defined as a 1.48-point change, using
      Patient Global Assessment as an anchor. Mean changes from baseline in ISI scores
      with tofacitinib were significantly greater than placebo by Day 2 and exceeded
      the clinically important difference by Week 4 and Week 2 for tofacitinib 5 and 10
      mg twice daily, respectively. The sound psychometric properties of the ISI as an
      assessment tool for pruritus in psoriasis were confirmed. Tofacitinib provided
      clinically meaningful improvements in psoriatic pruritus versus placebo.

PMID- 29182791
TI  - Substance P Antagonist Aprepitant Shows no Additive Effect Compared with
      Standardized Topical Treatment Alone in Patients with Atopic Dermatitis.
AB  - Atopic dermatitis (AD) is a chronic, itchy, inflammatory skin disorder that may
      worsen due to stress and anxiety. Tachykinins have been suggested to be involved
      in the inflammation in AD, as well as pruritus. Aprepitant is a NK-1 receptor
      antagonist. This open randomized trial evaluated the effect of aprepitant added
      to topical treatment in adult patients with moderate-severe AD. The treatment
      group (n = 19) received 80 mg/day aprepitant for 7 days as a supplement to
      standardized topical treatment with a moderately strong steroid and a
      moisturizer. The control group (n = 20) received topical treatment alone.
      Patients were monitored for the extent of the disease (using SCORing of Atopic
      Dermatitis; SCORAD), pruritus, and scratching movements. In both the aprepitant
      treated and the control groups there was a decrease in SCORAD, pruritus and
      scratching movements. However, there was no significant additional improvement in
      any of these parameters in the aprepitant-treated group compared with the control
      group.

PMID- 29182792
TI  - Ex vivo Culture of Duodenal Biopsies from Patients with Dermatitis Herpetiformis
      Indicates that Transglutaminase 3 Antibody Production Occurs in the Gut.
AB  - Coeliac disease and dermatitis herpetiformis (DH) are characterized by
      autoantibodies targeting transglutaminase (TG)2 and TG3, respectively. Previous
      studies show that TG2 antibodies are produced in the gut and can be assessed in
      organ culture of small-intestinal biopsies from patients with coeliac disease.
      Thus far, no studies have investigated TG3 antibodies in organ culture of
      biopsies from patients with DH, or exploited the method in DH. The aim of this
      study was to investigate TG3 and TG2 antibody responses in serum and small
      intestinal biopsies from patients with DH with active disease, and from those in
      remission. The majority of patients with DH were negative for both serum and
      organ culture medium TG2-targeting antibodies. Surprisingly, patients with active
      DH secreted TG3 antibodies into the culture medium despite seronegativity. In
      patients secreting high levels of TG3 antibodies into the culture medium, we also
      detected TG3-antibody-positive cells in the small-intestinal mucosa. These
      findings suggest that TG3 antibodies can be investigated in the organ culture
      system and that their secretion occurs in the small intestine, especially in
      active DH.

PMID- 29182794
TI  - Acquired Transverse Stripes on the Fingernails: A Quiz.

PMID- 29182793
TI  - Atypical Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6 in Denmark: A
      Diagnostic Mimicker.
AB  - Since 2008, outbreaks of atypical hand, foot, and mouth disease (HFMD) in
      children and adults have been reported worldwide. The majority of these outbreaks
      are caused by a new lineage of Coxsackie virus A6 (CV-A6) presenting a more
      severe clinical phenotype than the classical childhood HFMD caused by CV-A16.
      Between June 2014 and January 2016, 23 cases of atypical HFMD disease presented
      at a Dermatology Department at a regional University Hospital in Denmark.
      Patients were referred by general practitioners and dermatologists with a variety
      of clinical diagnoses, including eczema herpeticum, vasculitis, syphilis,
      dermatophytid, erythema multiforme and Stevens-Johnson syndrome. Three adults and
      3 children required hospitalization due to extensive skin involvement and fever.
      All reported patients had laboratory-confirmed enterovirus infection. This study
      demonstrated an upsurge in atypical HFMD caused by CV-A6 in the Region of
      Southern Denmark and that atypical HFMD can be difficult to diagnose clinically
      as it may mimic other severe skin diseases.

PMID- 29182795
TI  - Epidermolysis Bullosa (EB) Acquisita in an Adult Patient with Previously
      Unrecognized Mild Dystrophic EB and Biallelic COL7A1 Mutations.
AB  - Circulating anti-type VII collagen autoantibodies are frequently detected in
      patients with recessive dystrophic epidermolysis bullosa (RDEB). However,
      evidence supporting their pathogenic role in inducing epidermolysis bullosa
      acquisita (EBA) has been provided for only one individual with dominant
      dystrophic epidermolysis bullosa (DDEB). We describe here a patient who presented
      with dystrophic toenails since early childhood and developed trauma-induced skin
      blisters and oral erosions at age 26 years. Direct immunofluorescence showed IgG
      deposits with a u-serrated pattern along the cutaneous basement membrane zone,
      while no change in the expression of collagen VII could be detected by antigen
      mapping. High-titre anti-collagen VII antibodies were detected by enzyme-linked
      immunoassay (ELISA). In parallel, sequencing of epidermolysis bullosa (EB) genes
      identified compound heterozygous COL7A1 missense c.410G>A (p.Arg137Gln) and
      splicing c.3674C>T (p.Ala1225_Gln1241del) mutations, previously unrecognized in
      dystrophic epidermolysis bullosa (DEB). Thus, our patient had RDEB "nails-only"
      and developed mechanobullous EBA in adulthood. These data support a pathogenic
      role of circulating autoantibodies to collagen VII in inducing EBA in selected
      patients with DEB. Unforeseen worsening of skin symptoms in DEB should prompt
      laboratory investigations for EBA.

PMID- 29182796
TI  - Nodular Melanoma: A Histopathologic Entity?

PMID- 29182797
TI  - Palliative chemotherapy and targeted therapies for esophageal and
      gastroesophageal junction cancer.
AB  - BACKGROUND: Almost half of people with esophageal or gastroesophageal junction
      cancer have metastatic disease at the time of diagnosis. Chemotherapy and
      targeted therapies are increasingly used with a palliative intent to control
      tumor growth, improve quality of life, and prolong survival. To date, and with
      the exception of ramucirumab, evidence for the efficacy of palliative treatments
      for esophageal and gastroesophageal cancer is lacking. OBJECTIVES: To assess the
      effects of cytostatic or targeted therapy for treating esophageal or
      gastroesophageal junction cancer with palliative intent. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
      Embase, the Web of Science, PubMed Publisher, Google Scholar, and trial
      registries up to 13 May 2015, and we handsearched the reference lists of studies.
      We did not restrict the search to publications in English. Additional searches
      were run in September 2017 prior to publication, and they are listed in the
      'Studies awaiting assessment' section. SELECTION CRITERIA: We included randomized
      controlled trials (RCTs) on palliative chemotherapy and/or targeted therapy
      versus best supportive care or control in people with esophageal or
      gastroesophageal junction cancer. DATA COLLECTION AND ANALYSIS: Two authors
      independently extracted data. We assessed the quality and risk of bias of
      eligible studies according to the Cochrane Handbook for Systematic Reviews of
      Interventions. We calculated pooled estimates of effect using an inverse variance
      random-effects model for meta-analysis. MAIN RESULTS: We identified 41 RCTs with
      11,853 participants for inclusion in the review as well as 49 ongoing studies.
      For the main comparison of adding a cytostatic and/or targeted agent to a control
      arm, we included 11 studies with 1347 participants. This analysis demonstrated an
      increase in overall survival in favor of the arm with an additional cytostatic or
      targeted therapeutic agent with a hazard ratio (HR) of 0.75 (95% confidence
      interval (CI) 0.68 to 0.84, high-quality evidence). The median increased survival
      time was one month. Five studies in 750 participants contributed data to the
      comparison of palliative therapy versus best supportive care. We found a benefit
      in overall survival in favor of the group receiving palliative chemotherapy
      and/or targeted therapy compared to best supportive care (HR 0.81, 95% CI 0.71 to
      0.92, high-quality evidence). Subcomparisons including only people receiving
      second-line therapies, chemotherapies, targeted therapies, adenocarcinomas, and
      squamous cell carcinomas all showed a similar benefit. The only individual agent
      that more than one study found to improve both overall survival and progression
      free survival was ramucirumab. Palliative chemotherapy and/or targeted therapy
      increased the frequency of grade 3 or higher treatment-related toxicity. However,
      treatment-related deaths did not occur more frequently. Quality of life often
      improved in the arm with an additional agent. AUTHORS' CONCLUSIONS: People who
      receive more chemotherapeutic or targeted therapeutic agents have an increased
      overall survival compared to people who receive less. These agents, administered
      as both first-line or second-line treatments, also led to better overall survival
      than best supportive care. With the exception of ramucirumab, it remains unclear
      which other individual agents cause the survival benefit. Although treatment
      associated toxicities of grade 3 or more occurred more frequently in arms with an
      additional chemotherapy or targeted therapy agent, there is no evidence that
      palliative chemotherapy and/or targeted therapy decrease quality of life. Based
      on this meta-analysis, palliative chemotherapy and/or targeted therapy can be
      considered standard care for esophageal and gastroesophageal junction carcinoma.

PMID- 29182798
TI  - Pharmacological interventions for pain relief during orthodontic treatment.
AB  - BACKGROUND: Pain is a common side effect of orthodontic treatment. It increases
      in proportion to the amount of force applied to the teeth, and the type of
      orthodontic appliance used can affect the intensity of the pain. Pain during
      orthodontic treatment has been shown to be the most common reason for people
      wanting to discontinue treatment, and has been ranked as the worst aspect of
      treatment. Although pharmacological methods of pain relief have been
      investigated, there remains some uncertainty among orthodontists about which
      painkillers are most suitable and whether pre-emptive analgesia is beneficial. We
      conducted this Cochrane Review to assess and summarize the international evidence
      relating to the effectiveness of analgesics for preventing this unwanted side
      effect associated with orthodontic treatment. OBJECTIVES: The objectives of this
      review are to determine:- the effectiveness of drug interventions for pain relief
      during orthodontic treatment; and- whether there is a difference in the analgesic
      effect provided by different types, forms and doses of analgesia taken during
      orthodontic treatment. SEARCH METHODS: Cochrane Oral Health's Information
      Specialist searched the following databases: the Cochrane Oral Health Trials
      Register (to 19 June 2017), the Cochrane Central Register of Controlled Trials
      (CENTRAL;the Cochrane Library 2016, Issue 7), MEDLINE Ovid (1946 to 19 June
      2017), Embase Ovid (1980 to 19 June 2017) and CINAHL EBSCO (Cumulative Index to
      Nursing and Allied Health Literature; 1937 to 19 June 2017). The US National
      Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World
      Health Organization International Clinical Trials Registry Platform were searched
      on the 19 June 2017 for ongoing studies. We placed no restrictions on language or
      date of publication when searching the electronic databases. SELECTION CRITERIA:
      We included randomized controlled trials (RCTs) relating to pain control during
      orthodontic treatment. Pain could be measured on a visual analogue scale (VAS),
      numerical rating scale (NRS) or categorical scale. DATA COLLECTION AND ANALYSIS:
      Two review authors independently screened the search results, agreed the studies
      to be included and extracted information from the included studies regarding
      methods, participants, interventions, outcomes, harms and results. We planned to
      resolve any discrepancies or disagreements through discussion. We used the
      Cochrane 'Risk of bias' tool to assess the risk of bias in the studies. MAIN
      RESULTS: We identified 32 relevant RCTs, which included 3110 participants aged 9
      to 34 years, 2348 of whom we were able to include in our analyses. Seventeen of
      the studies had more than two arms. We were able to use data from 12 trials in
      meta-analyses that compared analgesics versus control (no treatment or a
      placebo); nine that compared non-steroidal anti-inflammatories (NSAIDs) versus
      paracetamol; and two that compared pre-emptive versus post-treatment ibuprofen
      for pain control following orthodontic treatment. One study provided data for the
      comparison of NSAIDs versus local anaesthetic.We found moderate-quality evidence
      that analgesics effectively reduced pain following orthodontic treatment when
      compared to no treatment or a placebo at 2 hours (mean difference (MD) -11.66 mm
      on a 0 to 100 mm VAS, 95% confidence interval (CI) -16.15 to -7.17; 10 studies,
      685 participants), 6 hours (MD -24.27 mm on a VAS, 95% CI -31.44 to -17.11; 9
      studies, 535 participants) and 24 hours (MD -21.19 mm on a VAS, 95% CI -28.31 to 
      14.06; 12 studies, 1012 participants).We did not find any evidence of a
      difference in efficacy between NSAID and paracetamol at 2, 6 or 24 hours (at 24
      hours: MD -0.51, 95% CI -8.93 to 7.92; 9 studies, 734 participants; low-quality
      evidence).Very low-quality evidence suggested pre-emptive ibuprofen gave better
      pain relief at 2 hours than ibuprofen taken post treatment (MD -11.30, 95% CI 
      16.27 to -6.33; one study, 41 participants), however, the difference was no
      longer significant at 6 or 24 hours.A single study of 48 participants compared
      topical NSAIDs versus local anaesthetic and showed no evidence of a difference in
      the effectiveness of the interventions (very low-quality evidence).Use of rescue
      analgesia was poorly reported. The very low-quality evidence did not show
      evidence of a difference between participants taking ibuprofen and participants
      taking paracetamol (relative risk (RR) 1.5, 95% CI 0.6 to 3.6). Nor did we find
      evidence of a difference between groups in likelihood of requiring rescue
      analgesia when ibuprofen was taken pre-emptively compared to after treatment (RR
      0.8, 95% CI 0.3 to 1.9).Adverse effects were identified in one study, with one
      participant developing a rash that required treatment with antihistamines. This
      was provisionally diagnosed as a hypersensitivity to paracetamol. AUTHORS'
      CONCLUSIONS: Analgesics are more effective at reducing pain following orthodontic
      treatment than placebo or no treatment. Low-quality evidence did not show a
      difference in effectiveness between systemic NSAIDs compared with paracetamol, or
      topical NSAIDs compared with local anaesthetic. More high-quality research is
      needed to investigate these comparisons, and to evaluate pre-emptive versus post
      treatment administration of analgesics.

PMID- 29182799
TI  - Inhaled magnesium sulfate in the treatment of acute asthma.
AB  - BACKGROUND: Asthma exacerbations can be frequent and range in severity from mild
      to life-threatening. The use of magnesium sulfate (MgSO4) is one of numerous
      treatment options available during acute exacerbations. While the efficacy of
      intravenous MgSO4 has been demonstrated, the role of inhaled MgSO4 is less clear.
      OBJECTIVES: To determine the efficacy and safety of inhaled MgSO4 administered in
      acute asthma. SPECIFIC AIMS: to quantify the effects of inhaled MgSO4 I) in
      addition to combination treatment with inhaled beta2-agonist and ipratropium
      bromide; ii) in addition to inhaled beta2-agonist; and iii) in comparison to
      inhaled beta2-agonist. SEARCH METHODS: We identified randomised controlled trials
      (RCTs) from the Cochrane Airways Group register of trials and online trials
      registries in September 2017. We supplemented these with searches of the
      reference lists of published studies and by contact with trialists. SELECTION
      CRITERIA: RCTs including adults or children with acute asthma were eligible for
      inclusion in the review. We included studies if patients were treated with
      nebulised MgSO4 alone or in combination with beta2-agonist or ipratropium bromide
      or both, and were compared with the same co-intervention alone or inactive
      control. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trial selection, data extraction and risk of bias. We made efforts to collect
      missing data from authors. We present results, with their 95% confidence
      intervals (CIs), as mean differences (MDs) or standardised mean differences
      (SMDs) for pulmonary function, clinical severity scores and vital signs; and risk
      ratios (RRs) for hospital admission. We used risk differences (RDs) to analyse
      adverse events because events were rare. MAIN RESULTS: Twenty-five trials (43
      references) of varying methodological quality were eligible; they included 2907
      randomised patients (2777 patients completed). Nine of the 25 included studies
      involved adults; four included adult and paediatric patients; eight studies
      enrolled paediatric patients; and in the remaining four studies the age of
      participants was not stated. The design, definitions, intervention and outcomes
      were different in all 25 studies; this heterogeneity made direct comparisons
      difficult. The quality of the evidence presented ranged from high to very low,
      with most outcomes graded as low or very low. This was largely due to concerns
      about the methodological quality of the included studies and imprecision in the
      pooled effect estimates. Inhaled magnesium sulfate in addition to inhaled beta2
      agonist and ipratropiumWe included seven studies in this comparison. Although
      some individual studies reported improvement in lung function indices favouring
      the intervention group, results were inconsistent overall and the largest study
      reporting this outcome found no between-group difference at 60 minutes (MD -0.3 %
      predicted peak expiratory flow rate (PEFR), 95% CI -2.71% to 2.11%). Admissions
      to hospital at initial presentation may be reduced by the addition of inhaled
      magnesium sulfate (RR 0.95, 95% CI 0.91 to 1.00; participants = 1308; studies =
      4; I2 = 52%) but no difference was detected for re-admissions or escalation of
      care to ITU/HDU. Serious adverse events during admission were rare. There was no
      difference between groups for all adverse events during admission (RD 0.01, 95%
      CI -0.03 to 0.05; participants = 1197; studies = 2). Inhaled magnesium sulfate in
      addition to inhaled beta2-agonistWe included 13 studies in this comparison.
      Although some individual studies reported improvement in lung function indices
      favouring the intervention group, none of the pooled results showed a conclusive
      benefit as measured by FEV1 or PEFR. Pooled results for hospital admission showed
      a point estimate that favoured the combination of MgSO4 and beta2-agonist, but
      the confidence interval includes the possibility of admissions increasing in the
      intervention group (RR 0.78, 95% CI 0.52 to 1.15; participants = 375; studies =
      6; I2 = 0%). There were no serious adverse events reported by any of the included
      studies and no between-group difference for all adverse events (RD -0.01, 95% CI 
      0.05 to 0.03; participants = 694; studies = 5). Inhaled magnesium sulfate versus
      inhaled beta2-agonistWe included four studies in this comparison. The evidence
      for the efficacy of beta2-agonists in acute asthma is well-established and
      therefore this could be considered a historical comparison. Two studies reported
      a benefit of beta2-agonist over MgSO4 alone for PEFR and two studies reported no
      difference; we did not pool these results. Admissions to hospital were only
      reported by one small study and events were rare, leading to an uncertain result.
      No serious adverse events were reported in any of the studies in this comparison;
      one small study reported mild to moderate adverse events but the result is
      imprecise. AUTHORS' CONCLUSIONS: Treatment with nebulised MgSO4 may result in
      modest additional benefits for lung function and hospital admission when added to
      inhaled beta2-agonists and ipratropium bromide, but our confidence in the
      evidence is low and there remains substantial uncertainty. The recent large, well
      designed trials have generally not demonstrated clinically important benefits.
      Nebulised MgSO4 does not appear to be associated with an increase in serious
      adverse events. Individual studies suggest that those with more severe attacks
      and attacks of shorter duration may experience a greater benefit but further
      research into subgroups is warranted.Despite including 24 trials in this review
      update we were unable to pool data for all outcomes of interest and this has
      limited the strength of the conclusions reached. A core outcomes set for studies
      in acute asthma is needed. This is particularly important in paediatric studies
      where measuring lung function at the time of an exacerbation may not be possible.
      Placebo-controlled trials in patients not responding to standard maximal
      treatment, including inhaled beta2-agonists and ipratropium bromide and systemic
      steroids, may help establish if nebulised MgSO4 has a role in acute asthma.
      However, the accumulating evidence suggests that a substantial benefit may be
      unlikely.

PMID- 29182801
TI  - [Harmonization of TSH Measurements.]
AB  - The measured concentration of thyroid stimulating hormone (TSH) differs depending
      on the reagents used. Harmonization of TSH is crucial because the decision limits
      are described in current clinical practice guide- lines as absolute values, e.g.
      2.5 mIU/L in early pregnancy. In this study, we tried to harmonize the report- ed
      concentrations of TSH using the all-procedure trimmed mean. TSH was measured in
      146 serum samples, with values ranging from 0.01 to 18.8 mIU/L, using 4
      immunoassays. The concentration of TSH was highest with E test TOSOH and lowest
      with LUMIPULSE. The concentrations with each reagent were recalculated with the
      following formulas: E test TOSOH 0.855x-0.014; ECLusys 0.993x+0.079; ARCHITECT
      1.041x- 0.010; and LUMIPULSE 1.096x-0.015. Recalculation eliminated the between
      assay discrepancy. These formulas may be used until harmonization of TSH is
      achieved by the International Federation of Clinical Chemistry and Laboratory
      Medicine (IFCC).

PMID- 29182800
TI  - Interventions to increase tuberculosis case detection at primary healthcare or
      community-level services.
AB  - BACKGROUND: Pulmonary tuberculosis is usually diagnosed when symptomatic
      individuals seek care at healthcare facilities, and healthcare workers have a
      minimal role in promoting the health-seeking behaviour. However, some policy
      specialists believe the healthcare system could be more active in tuberculosis
      diagnosis to increase tuberculosis case detection. OBJECTIVES: To evaluate the
      effectiveness of different strategies to increase tuberculosis case detection
      through improving access (geographical, financial, educational) to tuberculosis
      diagnosis at primary healthcare or community-level services. SEARCH METHODS: We
      searched the following databases for relevant studies up to 19 December 2016: the
      Cochrane Infectious Disease Group Specialized Register; the Cochrane Central
      Register of Controlled Trials (CENTRAL), published in the Cochrane Library, Issue
      12, 2016; MEDLINE; Embase; Science Citation Index Expanded, Social Sciences
      Citation Index; BIOSIS Previews; and Scopus. We also searched the World Health
      Organization International Clinical Trials Registry Platform (WHO ICTRP),
      ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing
      trials. SELECTION CRITERIA: Randomized and non-randomized controlled studies
      comparing any intervention that aims to improve access to a tuberculosis
      diagnosis, with no intervention or an alternative intervention. DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed trials for eligibility
      and risk of bias, and extracted data. We compared interventions using risk ratios
      (RR) and 95% confidence intervals (CI). We assessed the certainty of the evidence
      using the GRADE approach. MAIN RESULTS: We included nine cluster-randomized
      trials, one individual randomized trial, and seven non-randomized controlled
      studies. Nine studies were conducted in sub-Saharan Africa (Ethiopia, Nigeria,
      South Africa, Zambia, and Zimbabwe), six in Asia (Bangladesh, Cambodia, India,
      Nepal, and Pakistan), and two in South America (Brazil and Colombia); which are
      all high tuberculosis prevalence areas.Tuberculosis outreach screening, using
      house-to-house visits, sometimes combined with printed information about going to
      clinic, may increase tuberculosis case detection (RR 1.24, 95% CI 0.86 to 1.79; 4
      trials, 6,458,591 participants in 297 clusters, low-certainty evidence); and
      probably increases case detection in areas with tuberculosis prevalence of 5% or
      more (RR 1.52, 95% CI 1.10 to 2.09; 3 trials, 155,918 participants, moderate
      certainty evidence; prespecified stratified analysis). These interventions may
      lower the early default (prior to starting treatment) or default during treatment
      (RR 0.67, 95% CI 0.47 to 0.96; 3 trials, 849 participants, low-certainty
      evidence). However, this intervention may have may have little or no effect on
      treatment success (RR 1.07, 95% CI 1.00 to 1.15; 3 trials, 849 participants, low
      certainty evidence), and we do not know if there is an effect on treatment
      failure or mortality. One study investigated long-term prevalence in the
      community, but with no clear effect due to imprecision and differences in care
      between the two groups (RR 1.14, 95% CI 0.65 to 2.00; 1 trial, 556,836
      participants, very low-certainty evidence).Four studies examined health promotion
      activities to encourage people to attend for screening, including mass media
      strategies and more locally organized activities. There was some increase, but
      this could have been related to temporal trends, with no corresponding increase
      in case notifications, and no evidence of an effect on long-term tuberculosis
      prevalence. Two studies examined the effects of two to six nurse practitioner
      educational sessions in tuberculosis diagnosis, with no clear effect on
      tuberculosis cases detected. One trial compared mobile clinics every five days
      with house-to-house screening every six months, and showed an increase in
      tuberculosis cases.There was also insufficient evidence to determine if sustained
      improvements in case detection impact on long-term tuberculosis prevalence; this
      was evaluated in one study, which indicated little or no effect after four years
      of either contact tracing, extensive health promotion activities, or both (RR
      1.31, 95% CI 0.75 to 2.30; 1 study, 405,788 participants in 12 clusters, very low
      certainty evidence). AUTHORS' CONCLUSIONS: The available evidence demonstrates
      that when used in appropriate settings, active case-finding approaches may result
      in increase in tuberculosis case detection in the short term. The effect of
      active case finding on treatment outcome needs to be further evaluated in
      sufficiently powered studies.

PMID- 29182802
TI  - [Haplotype Analysis of Coagulation Factor VII Gene in a Patient with Congenital
      Coagulation Factor VII Deficiency with Heterozygous p.Arg337Cys Mutation and
      o.Aro413Gin Polymorphism..]
AB  - Congenital coagulation factor VII (FVII) deficiency is a rare hemorrhagic disease
      with an autosomal reces- sive inheritance pattern. We analyzed coagulation factor
      VII gene (F7) of a patient with FVII deficiency and used expression studies to
      investigate the effect of a missense mutation on FVII secretion. The proband, a
      69-year-old Japanese woman, had a history of postpartum bleeding and excessive
      bleeding after dental extrac- tion. She was found to have mildly increased PT-INR
      (1.17) before an ophthalmic operation. FVII activity and antigen were reduced
      (29.0% and 32.8%). Suspecting that the proband was FVII deficient, we analyzed F7
      of the patient. Sequence analysis revealed that the patient was heterozygous for
      a point mutation (p.Arg337Cys) in the catalytic domain and polymorphisms: the
      decanucleotide insertion at the promoter re- gion, dimorphism (c.525C >T) in exon
      5, and p.Arg413Gln in exon 8. Haplotype analysis clarified that p.Arg337Cys was
      located on the p.Arg413 allele (Ml allele). The other allele had the p.Arg413Gln
      polymor- phism(M2 allele) which is known to produce less FVII. Expression studies
      revealed that p.Arg337Cys causes impairment of FVII secretion. Insufficient
      secretion of FVII arising from both the p.Arg337Cys/M1 allele and the p.Arg337/M2
      allele might lower the FVII level of this patient(<50%). The FVII level in a
      heterozygous FVII deficient patient might be influenced by F7 polymorphisms on
      the normal allele. There- fore, genetic analyses are important for the diagnosis
      of heterozygous FVII deficiency.

PMID- 29182803
TI  - [The Kidney and Comprehensive Medicine in Humans.]
AB  - The organs of the body do not only function independently. Various organs work
      together to form a net- work, and it has been suggested that this is how
      homeostasis is maintained in the human body. The kidneys play a vital role in
      maintaining homeostasis through regulating processes such as metabolism and
      endocrine activity. In fact, the onset, progression, and chronic nature of kidney
      disease leads to the development of cardiovascular disease that can itself lead
      to systemic organ damage. We refer to this attempt to elucidate such a bodily
      network as the "Comprehensive Medicine in Humans" study. We hope to reveal such
      mecha- nisms, and develop new diagnostic and treatment methods. We previously
      reported on nephro-vascular and nephro-pulmonary networks. Chronic kidney disease
      (CKD) patients, even when not suffering from diabe- tes mellitus, have been shown
      to exhibit a progression in atherosclerosis. Furthermore, a decline in the kidney
      function is closely linked to a decline in the pulmonary diffusion capacity. It
      has therefore been sug- gested that networks exist involving the kidneys and
      various other organs. Increasing CKD rates in a highly aged society, along with
      accompanying illnesses, can be understood from a whole-body network perspective.
      We aim to gain knowledge that can aid in disease prevention, as well as help
      develop new diagnostic methods and treatments for patients suffering from kidney
      disease.

PMID- 29182804
TI  - [Breakthrough Technologies: Liquid Biopsy -Chairmen's Introductory Remarks.]
AB  - To date, liquid biopsies have generated much interest as they involve minimally
      invasive blood tests, pro- vide an ongoing picture of a patient's cancer, and
      offer valuable insight into the best treatment. Liquid biop- sies detect
      circulating tumor cells (CTCs), fragments of tumor DNA and exosomes that are shed
      into the blood from the primary tumor and from metastatic sites. Liquid biopsies
      offer what tissue biopsies cannot due to risks to the patients and costs. Liquid
      biopsies allow the monitoring of genomic changes in tumors for the diagnosis of
      early and recurrent cancer and drug effects. In the future, instead of extensive
      imaging and invasive tissue biopsies, liquid biopsies could be used to guide
      cancer treatment decisions and even screen for tumors that are not vet visible on
      imaging.

PMID- 29182805
TI  - [Liquid Biopsy: Challenges and Possibilities Regarding Its Clinical Application.]
AB  - Cell-free DNA is "Fragmented DNA found in circulation in the Cell-free component
      of whole blood". Cell-free DNA derived from tumors is expressed as circulating
      tumor DNA. Examination of circulating tu- mor DNA for genetic alterations present
      in the tumor tissue is defined as liquid biopsy. Currently in the cancer field,
      Cell-free DNA or CTC (Circulating tumor cells) is the main target of "Liquid
      Biopsy". Acquir- ing Cell-free DNA or CTC presents little challenge because of
      the recent technological developments. However, we need to improve the efficiency
      of CTC retrieval, and we also need to establish how to culture the retrieved
      CTCs. For clinical applications, PGx (Pharmacogenomics) and PGt
      (Pharmacogenetics) fol- lowing NGS (Next Generation Sequencing) are attractive
      areas for new and future applications. The intro- duction of "Liquid Biopsy" to
      the area of clinical trials is already in progress. As an expert group, members
      of the JSLM (Japanese Society of Laboratory Medicine) need to indicate the
      presence of quality control or quality management in the area of "Liquid Biopsy".
      Besides these quality issues, we, as clinical pathologists, need to think about
      harmonizing our expertise with surgical pathologists, who have historically
      handled clas- sical biopsies of solid samples. The field of "Liquid Biopsy" has
      marked potential; however, we need to overcome various obstacles to realize this.

PMID- 29182806
TI  - [Circulating Tumor DNA (ctDNA) Detection Using BEAMing and Its Clinical
      Significance.]
AB  - In cancer, companion diagnostics accompanied by molecular-targeted drugs have
      been developed and launched over the last decade, leading to marked improvements
      of patients' treatments and outcomes. Alt- hough most of them are tested using
      tissue samples, sometimes it is difficult to obtain a biopsy for some types of
      cancers because of the patient's risk and performance status. Recently, extensive
      clinical research regarding "Liquid Biopsy", such as circulating tumor DNA
      (ctDNA), has been performed. It is considered that "Liquid Biopsy" has the
      potential to overcome the issue of tissue-based molecular diagnostics. "BEAMing"
      is one of the digital PCR methods invented by Prof. Bert Vogelstein's group from
      Johns Hop- kins University. This technology enables highly sensitive detection,
      at 0.01% of ctDNA in plasma, which outperforms general PCR methods. Regarding
      BEAMing, extensive research on the clinical significance of ctDNA detection has
      been done, especially in three fields: response prediction, response/recurrence
      monitoring, and molecular-targeted drug resistance monitoring. In this article, I
      will discuss the possibility of BEAMing and ctDNA testing as future diagnostics.

PMID- 29182807
TI  - [Application of Liquid Biopsy for Lung Cancer Treatment.]
AB  - Liquid biopsy is defined as a non-invasive blood test that detects features of
      tumor cells, which are shed into the blood stream from the primary tumor and/or
      metastatic sites. This method is developing based on research on circulating
      tumor cells (CTCs) and the circulating free/fragments of tumor DNA (cfDNA). CfDNA
      can be detected in the absence of detectable CTCs, and has been shown to increase
      with the disease condition. The detection of cfDNA can be used for tumor
      genotyping, monitoring of the tumor burden, and monitoring minimal residual
      diseases, and recent results showed that cfDNA is a highly specific biomarker
      with intermediate sensitivity. Liquid biopsy with cfDNA is promising, and is
      becoming an alternative to re- biopsy. However, there are some caveats: it has
      not been elucidated which patients and tumor types can be accessed with cfDNA.
      Further research is warranted.

PMID- 29182808
TI  - [Japanese International Volunteer Activities for Medical Aid -Chairman's
      Introductory Remarks.]
AB  - We held a symposium on international volunteer activities for medical support in
      foreign countries at the 62nd annual meeting of the Japanese Society of
      Laboratory Medicine. Here, we introduce two well-known international volunteer
      groups, the Peshawar-kai and Rocinantes. The two groups have continued various
      forms of medical assistance for a long time in Afghanistan and Sudan,
      respectively, where medical services are severely lacking. In this symposium, we
      would like to consider what is required in the countries, what is being done
      there, why they continue their activities, how we can support them, and, finally,
      what is the true goal of medical volunteer activities.

PMID- 29182809
TI  - [Current Status and Issues of Clinical Laboratory Testing Expanding into Health
      Care: How to Challenge Experts of Laboratory Medicine -Remark of Moderators.]
AB  - Point-of-Care Testing (POCT) has been increasingly implemented in healthcare, on
      the basis of advances in analysis and information technologies. Wherever POCT is
      implemented, it needs to be properly and safe- ly performed. However, a concern
      has been raised that it is preformed without training and support from the
      clinical laboratory and, thus, testing reliability and patient safety are not
      sufficiently ensured. Laboratory professionals and experts are expected to play
      an important role in the solution of this issue, through provid- ing guidance and
      support in the proper implementation and patient safety of POCT. Hence, this
      symposium was organized to summarize current situations and issues of POCT
      expanding into health care, the communi- ty, and home, and to clarify the way to
      challenge them as laboratory professionals for increased reliability and
      confidence on performing POCT, contributing to the cost-effectiveness and quality
      of health-care services.

PMID- 29182810
TI  - [The Technical Innovation of Medical Engineering and Application Development in
      POCT Devices.]
AB  - Medical doctors have been utilizing POCT devices at POC sites (ER, ICU, and
      operation rooms). Now, POCT devices are used by health care professionals in the
      physician's office and also for home healthcare. Home healthcare (welfare/nursing
      care) is a focus area of the MHLW initiative to develop healthcare in order to
      resolve the "2025 problem". The role of POCT is important in resolving this
      issue.

PMID- 29182811
TI  - [Present Status and Problems of Laboratory Test in a Community and at Home:
      "Sample Measurement Room", Self-Test and Mail-in Test.]
AB  - In this review, the present status and problems of laboratory tests outside
      traditional healthcare were dis- cussed. The test group includes the "sample
      measurement room", self-test, and mail-in test. They will be classified by 2 X 2
      viewpoints, sampling/measurement X place/person. As for the "sample measurement
      room", consultation based on the results cannot be recommended, even if the
      results are abnormal, although this is often misunderstood. The problems of the
      "sample measurement room", self-test, and mail-in test can be considered from the
      viewpoints mentioned above. A sample extraction defect, infection between
      persons, the data instability by preservation, measurement error, and
      insufficient quality control are thought to be examples.

PMID- 29182812
TI  - [Respiratory Function Tests as Physiological Examination in Home Health Care 
      Pulse Oximeter, Peak Flow Meter, and NO Measurement Apparatus.]
AB  - Daily monitoring of patients with chronic respiratory failure or bronchial asthma
      to prevent their disease deterioration is required. In home health care, the
      pulse oximeter for chronic respiratory failure during home oxygen therapy and the
      peak flow meter or the expiratory nitric oxide (NO) measurement apparatus for
      bronchial asthma are important. As there are many pitfalls in interpreting the
      test results, appropriate in- formation needs to be conveyed from the physicians
      to patients.

PMID- 29182813
TI  - [Circulatory Function Tests for Home & Community Use.]
AB  - Currently, the main circulatory function-testing tools for home use are blood
      pressure monitors and elec- trocardiography devices. Just like blood pressure
      monitors that are already widespread for home use, some devices with an
      electrocardiographic function have recently become available for purchase for
      personal use by the general public. On the other hand, clinic equipment on loan
      from doctors to patients in need can perform circulatory function tests like 24
      hour ambulatory blood pressure monitoring (ABPM), Holter monitoring, and real
      time electrocardiography. We introduce the actual clinical usage of ABPM and real
      time electro- cardiography, and discuss the usefulness of these procedures. ABPM
      uses a blood pressure measurement device worn on the body for 24 hours a day to
      measure blood pressure at regular intervals. This makes it possible to check
      blood pressure changes throughout the day in a way in which conventional home-use
      blood pressure monitors cannot, like during sleep. This method al- lows the
      identification of masked hypertension like early-morning and nocturnal
      hypertension, stress hyper- tension including workplace hypertension, and white
      coat hypertension that only occurs in the doctor's office. Under routine care,
      there are few opportunities to perform electrocardiography at the time a patient
      is experiencing symptoms. Now, real-time electrocardiography has begun to be used
      in routine care, and pa- tients can record an electrocardiogram by themselves
      anytime, anywhere, and send the data by telephone or the Internet for analysis
      and diagnosis. Transmission-capable electrocardiography devices can play an im-
      portant role in the event of dangerous symptoms like arrhythmia, angina, or acute
      myocardial infarction. The spread of ABPM and event heart monitors is likely to
      make the early treatment and prevention of stroke and heart disease possible. We
      are expecting rapid development in this field in the future.

PMID- 29182814
TI  - [Global Trends in the Use of Point-of-Care Testing Devices and Efforts toward
      Standardization.]
AB  - Advances in testing and information technologies have expanded the availability
      of Point-of-Care Testing (POCT) devices not only in healthcare but also in non
      healthcare settings. POCT laboratory accreditation under ISO 22870 has been
      implemented in conjunction with ISO 15189 in European countries. A markedly
      increasing number of facilities are performing POCT in non-healthcare settings in
      the United States with a certificate of waiver and in European countries;
      concerns are being raised on the lack of oversight and re- quirements for
      personnel qualifications and training. Centers for Disease Control and Prevention
      have been making efforts to develop educational tools. In ISO Technical Committee
      212 (ISO/TC212) on clinical labor- atory testing and in vitro diagnostic test
      systems, guidance for POCT operators is proposed, being designed as a document
      for operators in healthcare and non-healthcare settings who lack specific medical
      laboratory training. In Japan, on the basis of the international efforts on
      standardization and quality assurance, nation- wide efforts are necessary for
      increased reliability and confidence on performing POCT to promote the cost-
      effectiveness and quality of healthcare services.

PMID- 29182815
TI  - [Challenges and Potentialities of Biobank Projects -Chairman's Introductory
      Remarks.]
AB  - At the symposium entitled "challenging future of bio-bank business," the
      following topics were presented: 1) Bio-bank in the field of preemptive diagnosis
      by Prof. Saito (Fujita Health University), comprising personal health records of
      healthy individuals (3,000 as of Nov., 2015) consolidated with bio-resources
      under the or- ganization of the Resource Center for Health Science; 2) Cord blood
      banking by Mr. Asai (Stem Cell Institute Inc.), which was started in 1999,
      including mesenchymal stem cells for autologous purposes; 3) Bio-banking for
      regenerative medicine by Mr. Esaki (Healthcare Service Division of METI), in
      which stem cells from cord blood, surgical tissues, and dental pulp targeted for
      allogeneic purposes were emphasized; 4) Demonstration of a reference/search
      program for bio-bank business with a focus on medical information, a dietary
      question- naire (BDHQ), and stress questionnaires (GHQ-28 and CES-D) by Mr.
      Sakurai (SEIKOTEC Co., Ltd.). In iddition. Mr. Mivata (Nikkei BP. Inc.) helned
      facilitate the symposium.

PMID- 29182816
TI  - [Bio-Resources and Database for Preemptive Medicine.]
AB  - Establishing a primary defense for the improvement of individual quality of life
      by epidemiology and various clinical studies applying bio-resources/database
      analysis is very important. Furthermore, recent studies on understanding the
      epigenetic regulatory mechanisms of developmental origins of health and diseases
      are attracting increasing interest. Therefore, the storing of not only bio-fluid
      (i.e., blood, urine) but also certain tissues (i.e., placenta, cord) is very
      important for research. The Resource Center for Health Science (RECHS) and Bio
      databases Institute of Reproductive and Developmental Medicine (BIRD) have estab-
      lished Bio-bank and initiated a project based on the development and utilization
      of bio-resources/database, comprising personal health records (PHR), such as
      health/medical records including individual records of daily diet and exercise,
      physically consolidated with bio-resources, taken from the same individuals.
      These Bio-Resources/Database projects are very important for the establishment of
      preemptive medicine and un- derstanding the mechanisms of the developmental
      origins of health and diseases.

PMID- 29182817
TI  - [Signs can be Found in "Clinical Laboratory Values" and "Ultrasonographic
      Findings" -Chairmen's Introductory Remarks.]
AB  - Many examinations have limitations, including specificity. Therefore, multiple
      examinations should be combined for practical diagnosis to facilitate treatment.
      In symposium 14 (ultrasound and clinical examina- tion), 5 speakers presented how
      to combine diagnostic methods in their clinical practice. This symposium
      highlighted the importance of the comprehensive management of multiple
      examinations for optimal patient care.

PMID- 29182818
TI  - [View of Clinical Laboratory Physician on Pathophysiological Analysis by Close
      Cooperation of Clinical Laboratory and Ultrasonography.]
AB  - I want to give my opinion on what ultrasonography and the clinical laboratory
      should be to improve medical care. First, the close collaboration between
      ultrasonography and the clinical laboratory is the most im- portant. The
      development of technology and translation into the hands of medical technologists
      have been increasing the usefulness of ultrasonography to provide information for
      medical care. So, information should be used to interpret and report,
      respectively. The clinical research should be driven forward by collabora- tion
      and will result in improving medical care. Second, the system and culture of
      quality assurance should be established for ultrasonography as was done for
      clinical chemistry, hematology, etc. At that time, medical technologists who
      performed ultrasonography had to be aware that their abilities would be evaluated
      by oth- ers. Finally, it is important for medical technologists to educate young
      doctors not only on how to perform ultrasonography but also how to interpret
      images, because ultrasonography has been moving into the hands of medical
      technologists from doctors. Their sensitivity and view of life affect their
      works. I am sure of their importance in the clinical laboratory.

PMID- 29182819
TI  - [The Latest Findings in Liver Diseases -Chairman's Introductory Remarks.]
AB  - Symposium 15 entitled: "the latest findings in liver diseases", was held at the
      62nd Annual Meeting of the Japanese Society of Laboratory Medicine last year in
      Gifu. It is well-known that there have been marked changes in clinical practice
      for liver diseases, such as the development of directly acting antivirals for
      hepati- tis C virus, elucidation of the reactivation of hepatitis B virus, and
      the increase in the number of patients with non-alcoholic fatty liver disease and
      non-alcoholic steatohepatitis. Three speakers, Professor Junko Tanaka from
      Hiroshima University, Professor Yasuhito Tanaka from Nagoya City University, and
      Assistant Director Toshihide Shima from Saiseikai Suita Hospital, were invited to
      give a lecture regarding the epidemiological aspects of viral hepatitis, the
      reactivation of hepatitis B virus, and the current status and monitoring of non-B
      non-C liver diseases, respectively. This manuscript briefly summarizes the
      background of this symposium.

PMID- 29182820
TI  - [Epidemiology of Hepatitis Virus Infection and Its Control from the
      Epidemiological Point of View.]
AB  - In Japan, hepatitis and liver cancer measures, based on the hepatitis Basic
      Measures Law, have been pro- moted for 25 years with a focus on advancing the
      diagnosis, treatment, and inspection. In 2011, the estimated number of people
      persistently infected with the hepatitis virus in Japan was esti- mated to be
      about 2.1-2.8 per million people. In addition, "persistent infections latent in
      society of people unaware of their infection" has been estimated to involve
      777,000 people. Since it is now a time of introducing new drugs for effective
      anti-viral therapy, in order to continue to more effectively implement the
      hepatitis and liver cancer measures, regional cooperation, such as the
      construction of a liver disease patient follow-up system, is important.

PMID- 29182821
TI  - [Present State of Non-B Non-C Liver Disease-and Its Monitoring.]
AB  - As the prevalence of lifestyle-related diseases increases, the number of
      individuals who have abnormal liver function test results with negative HBs
      antigen and anti-HCV(non-B non-C liver diseases) has been increasing. Non-B non-C
      liver diseases consist mainly of nonalcoholic fatty liver disease (NAFLD) and al-
      coholic liver disease. Non-B non-C liver cancers have been increasing in number.
      The identification of individuals with high risks of liver cancer is crucial for
      their early diagnosis and treatment. Among NAFLD individuals, nonalcoholic
      steatohepatitis (NASH) patients with advanced liver fibrosis have a high risk of
      non-B non-C liver cancers. For the diagnosis of NASH with advanced liver
      fibrosis, useful parameters are as follows: 1) high value of liver fibrosis
      markers, such as type 4 collagen 7S, 2) low platelet count (lower than 19 X
      104/pL), 3) high value using a scoring system, such as the NAFLD fibrosis score
      and FIB-4 index, 4) high stiffness value measured by elastography, 5) advanced
      age, and 6) comorbidity of 3 or 4 types of lifestyle-related diseases. Alcohol
      drinkers consuming more than 60 g of ethanol a day are at risk of liver cancer.
      Obesity and diabetes mellitus are also risk factors. Individuals as described
      above are at risk of non-B non-C liver cancers. AFP is unlikely to show a high
      value in NASH liver cancer. Regular examination (every 6 months) with sonography
      and PIVKA-II is rec- ommended for the early diagnosis of non-B non-C liver
      cancers.

PMID- 29182822
TI  - [[GUIDELINES FOR THE PREVENTION, MONITORING AND THERAPY OF CHRONIC KIDNEY DISEASE
      METABOLIC BONE DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE].]
AB  - Chronic kidney disease (CKD) is a systemic disease with numerous complications
      associated with increased morbidity and mortality. Chronic kidney disease
      metabolic bone disease (CKD-MBD) starts at early stages of CKD with phosphorus
      accumulation and consequent initiation of numerous events that result with the
      development of secondary hyperparathyroidism with changes on bones and
      extraskeletal tissues. The most important and clinically most relevant
      consequences of CKD-MBD are vascular calcifications which contribute to
      cardiovascular mortality. Patients with the increased risk for the development of
      CKD-MBD should be recognized and treated. Prevention is the most important
      therapeutic option. The first step should be nutritional counseling with vitamin
      supplementation if necessary and correction of mineral status. Progression of CKD
      requires more intensive medicamentous treatment with the additional correction of
      metabolic acidosis and anemia. Renal replacement therapy should be timely
      initiated, with the adequate dose of dislaysis. Ideally, preemptive renal
      transplantion should be offered in individuals without contraindication for
      immunosuppressive therapy.

PMID- 29182824
TI  - PATHOLOGICAL CHANGES OF RENAL ARTERIES IN PATIENTS WITH RENAL CELL CARCINOMA.
AB  - Renal cell carcinoma is the ninth most common cancer in the world. It may have a
      varied microscopic appear- ance, and the most common histopathological type is
      clear cell carcinoma. The most common pathological changes of renal arteries are
      atherosclerosis and fibromuscular dysplasia (FMD). During histopathological
      evaluation of a kidney specimen containing carcinoma, the renal vein is routinely
      analyzed, while the renal artery is usually given little attention. Our stud- ies
      have shown that pathological changes of renal arteries are significantly more
      frequent in the group of patients with renal cell carcinoma compared with the
      control group and the group of patients with non-tumor kidney diseases. These
      relations led us to the conclusion that the onset of renal artery changes is not
      prior to the carcinoma or non-tumor diseases and that they are formed
      simultaneously or as a consequence. Further studies should be aimed at
      determining the incidence of these changes in a larger number of samples and the
      detection of their possible correlation with renal cell carcinoma.

PMID- 29182823
TI  - GUIDELINES FOR THE PREVENTION, DETECTION AND THERAPY OF VITAMIN D DEFICIENCY IN
      ADULTS.
AB  - It is estimated that over one billion of people around the globe have low serum
      values of vitamin D, therefore, we can consider vitamin D deficiency as a
      pandemic and public health problem. Geographic position of Croatia, especially
      the continental part of the country, is a risk factor for the development of
      deficiency of vitamin D in the population. The aim of these guidelines is to
      provide the clinicians with easy and comprehensive tool for prevention, detection
      and therapy of vitamin D deficienney in healthy population and various groups of
      patients. They were made as a result of collaboration of clinicians of different
      backgrounds who are dealing with patients at risk of vitamin D deficiency. These
      guidelines are evi- dence-based, according to GRADE-system (Grading of
      Recommendations, Assessment, Development and Evaluation), which describes the
      level of evidence and strength of recommendation. The main conclusions address
      the recommended serum vitamin D values in the population which should be between
      75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages
      of vitamin D in order to reach the adequate levels of serum vitamin D.

PMID- 29182825
TI  - SOCIODEMOGRAPHIC CHARACTERISTICS INFLUENCE PAIN PERCEPTION IN NON-SMALL CELL LUNG
      CANCER PATIENTS.
AB  - BACKGROUND: Lung cancer is the most common malignant disease in men and the third
      most common in women worldwide. Pain in these patients is a leading and
      debilitating symptom, among others. OBJECTIVES: The aim of this research was to
      determine the relationship between the sociodemographic characteristics and pain
      perception, as measured by visual analogue scale for pain, in patients with non
      small cell lung cancer. METHODS: This observational, single centre study included
      both a cross-sectional and prospective cohort design. RESULTS: Forty-one patients
      with a median age of 61 years (range 56-68) were included. This study showed that
      subjective perception of pain is related to age and place of residence. Younger
      patients ( <= 60 years old, p=0.026) and those residing in cities (p=0.03 1)
      reported feeling worse pain. Age was independently and statistically associated
      with the relative relief of pain after analgesic therapy (Wald=5.914; ss=1;
      p=0.015). CONCLUSION: Age, lifestyle, place of residence, and mentality should be
      considered when evaluating pain percep- tion in patients suffering from chronic
      pain related to malignant disease in order to provide the best possible medical
      treat- ment with the goal of improving quality of life.

PMID- 29182826
TI  - IS THERE ANY ROOM FOR TENDOSCOPY IN THE SURGICAL TREATMENT OF POSTERIOR TIBIAL
      TENDON INSUFFICIENCY?
AB  - Posterior tibial tendon insufficiency (PTTI) is nowadays considered to be the
      main cause of adult-acquired flatfoot deformity (AAFD). The purpose of this study
      is to report the outcomes of tendoscopic treatment of tibialis poste- rior tendon
      (TP) in eleven patients with stage 1 or 2 PTTI and failed prior conservative
      treatment. Tendoscopy was carried out as a solitary procedure in 8 patients,
      while in 3 patients additional procedures such as ,,mini-open" tubularization of
      TP or anterior ankle arthroscopy were necessary. In a single patient transfer of
      flexor digitorum longus tendon was performed as a second stage surgery due to
      complete rupture of TP. Related with tendoscopic procedure, no complications were
      re- ported. TP tendoscopy is a useful and beneficial minimally invasive procedure
      to treat TP pathology at earlier stages of PTTI. It is a technically demanding
      procedure that requires extensive experience in arthroscopic management of small
      ioints and excellent knowledge of repional anatomy.

PMID- 29182827
TI  - GIANT CELL AORTITIS DIAGNOSED WITH PET/CT - PARANEOPLASTIC SYNDROME?
AB  - Vasculitides are heterogenic group of autoimmune connective tissue diseases which
      often present difficulties in early diagnosing. Giant cell arteritis is
      vasculitis of large and medium arteries. It predominantly presents with symptoms
      of affection of the external carotid artery branches. Furthermore, the only
      symptoms can be constitutional. In clinical practice, vasculitides are sometimes
      considered as paraneoplastic, but no definite association with malignancies has
      been established and the mechanisms are still debated. The gold standard for
      diagnosing giant cell arteritis is a positive temporal artery biopsy, but the
      results can often be false negative. Additionally, more than half of the patients
      have aorta and its main branches affected. Considering aforementioned, imaging
      studies are essential in confirming large-vessel vasculitis, amongst which is
      highly sensitive PET/CT. We present the case of a 70-year-old female patient with
      constitutional symptoms and elevated sedimentation rate. After extensive
      diagnostic tests, she was admitted to our Rheumatology unit. Aortitis of the
      abdominal aorta has been confirmed by PET/CT and after the introduction of
      glucocorticoids the disease soon went into clinical and laboratory remission.
      Shortly after aortitis has been diagnosed, lung carcinoma was revealed of which
      the patient died. At the time of the comprehensive diagnostics, there was no
      reasonable doubt for underlying malignoma. To the best of our knowledge, there
      are no recent publications concerning giant cell arteritis and neoplastic
      processes in the context of up-to-date non-invasive diagnostic methods (i.e.
      PET/CT). In the light of previous research results, we underline that the
      sensitivity of PET/CT is not satisfactory when estimating cancer dissemination in
      non-enlarged lymph nodes and that its value can at times be overestimated.

PMID- 29182828
TI  - APPROACH TO THE PATIENT WITH NONALCOHOLIC FATTY LIVER DISEASE.
AB  - XNonalcoholic fatty liver disease (NAFLD) has become a common cause of elevated
      liver tests. The association between fatty liver and metabolic syndrome (MS) is
      well documented and widely accepted. Cirrhosis due to nonalcoholic
      steatohepatitis (NASH) is currently the second most common indication for liver
      transplant with increasing incidence. Gastroenterologists/hepathologists and
      primary care physicians have more questions than answers regarding the NAFLD. The
      most common questions are which NAFLD patients have a risk of progression to
      NASH, fibrosis, cirrhosis and hepa- tocellular carcinoma, and which patients with
      NAFLD have a need for liver biopsy. In addition, a number of non-invasive
      diagnostic methods in the approach to the patient with NAFLD are investigated.
      How to approach these patients in routine clinical practice, is more of an art
      than a science at this time. In this article we will try to provide more recent
      recommenda- tions of how to approach the patients with NAFLD.

PMID- 29182829
TI  - [Chronic kidney disease and cardiovascular disease : progression of arterial
      diseases in chronic kidney disease.]

PMID- 29182830
TI  - [The clinical characteristics of hypertension in chronic kidney disease.]

PMID- 29182831
TI  - [Pathophysiology of atherosclerosis in chronic kidney disease.]

PMID- 29182832
TI  - [Pathophysiology and therapeutic strategies of nephrosclerosis in the ageing
      society, Japan.]

PMID- 29182833
TI  - [Singularity of coronary artery disease in chronic kidney disease.]

PMID- 29182834
TI  - [Cerebrovascular disease in chronic kidney disease.]

PMID- 29182835
TI  - [Chronic kidney disease and aortic lesions.]

PMID- 29182836
TI  - [CKD and Progression of PAD.]

PMID- 29182837
TI  - [Chronic kidney disease caused by cholesterol embolization syndrome.]

PMID- 29182838
TI  - [After 200 years, time to watch the step of stethoscope.]

PMID- 29182839
TI  - [A case of FPS (fasciitis-oanniculitis syndrome) mimicking SSc (systemic
      sclerosis).]

PMID- 29182840
TI  - [A cse f myocardial infarction due to tumor embolus from myxoma proved by
      thrombus auction catheter.]

PMID- 29182841
TI  - [A case report of a nephrotic syndrome on IgA nephropathy complicated by Kimura's
      disease.]

PMID- 29182843
TI  - [The Cutting-edge of Medicine ; The latest treatment for multiple sclerosis.]

PMID- 29182842
TI  - [Case Report ; Malignant catatonia in a patient with schizophrenia.]

PMID- 29182844
TI  - [The Cutting-edge of Medicine ; Current opinion concerning pulmonary
      sarcoidosis.]

PMID- 29182845
TI  - [Diagnosis at a Glance.]

PMID- 29182846
TI  - Highly Efficient Thin-Film Transistor via Cross-Linking of 1T Edge Functional 2H
      Molybdenum Disulfides.
AB  - Thin-film transistors (TFTs) have received great attention for their use in
      lightweight, large area, and wearable devices. However, low crystalline materials
      and inhomogeneous film formation limit the realization of high-quality electrical
      properties for channels in commercial TFTs, especially for flexible electronics.
      Here, we report a field-effect TFT fabricated via cross-linking of edge-1T basal
      2H MoS2 sheets that are prepared by edge functional exfoliation of bulk MoS2 with
      soft organic exfoliation reagents. For edge functional exfoliation, the
      electrophilic 4-carboxy-benzenediazonium used as the soft organic reagent attacks
      the nucleophilic thiolates exposed at the edge of the bulk MoS2 with the help of
      an amine catalyst, resulting in 1T edge-functional HOOC-benzene-2H basal MoS2
      nanosheets (e-MoS2). The cross-linking via hydrogen bonding of the negatively
      charged HOOC of the e-MoS2 sheets with the help of a cationic polymer,
      polydiallyldimethylammonium chloride, results in a good film formation for a
      channel of the solution processing TFT. The TFT exhibits an extremely high
      mobility of 170 cm2/(V s) at 1 V (on/off ratio of 106) on SiO2/Si substrate and
      also a high mobility of 36.34 cm2/(V s) (on/off ratio of 103) on PDMS/PET
      substrate.

PMID- 29182848
TI  - Self-Recovery Superhydrophobic Surfaces: Modular Design.
AB  - Superhydrophobicity, the enhanced hydrophobicity of surfaces decorated with
      textures of suitable size, is associated with a layer of gas trapped within
      surface roughness. The reduced liquid/solid contact makes superhydrophobicity
      attractive for many technological applications. This gas layer, however, can
      break down with the liquid completely wetting the surface. Experiments have shown
      that the recovery of the "suspended" superhydrophobic state from the wet one is
      difficult. Self-recovery-the spontaneous restoring of the gas layer at ambient
      conditions-is one of the dreams of research in superhydrophobicity as it would
      allow to overcome the fragility of superhydrophobicity. In this work we have
      performed a theoretical investigation of the wetting and recovery processes on a
      set of surfaces characterized by textures of different dimensions and morphology
      in order to elucidate the optimal parameters for avoiding wetting and achieving
      self-recovery. Results show that texture size in the nanometer range is a
      necessary but not sufficient condition for self-recovery: the geometry plays a
      crucial role, nanopillars prevent self-recovery, while surfaces with square pores
      exhibit self-recovery even at large positive pressures. However, the optimal
      morphology for self-recovery, the square pore, is suboptimal for the functional
      properties of the surface, for example, high slippage. Our calculations show that
      these two properties are related to regions of the texture separated in space:
      self-recovery is controlled by the characteristics of the bottom surface, while
      wetting and slip are controlled by the cavity mouth. We thus propose a modular
      design strategy which combines self-recovery and good functional properties:
      Square pores surmounted by ridges achieve self-recovery even at 2 MPa and have a
      very small liquid/solid contact area. The macroscopic calculations, which allowed
      us to efficiently devise design criteria, have been validated by atomistic
      simulations, with the optimal texture showing self-recovery on atomic time
      scales, tau ~ 2 ns.

PMID- 29182847
TI  - NRPS-Derived Isoquinolines and Lipopetides Mediate Antagonism between Plant
      Pathogenic Fungi and Bacteria.
AB  - Bacterial-fungal interactions are presumed to be mediated chiefly by small
      molecule signals; however, little is known about the signaling networks that
      regulate antagonistic relationships between pathogens. Here, we show that the
      ralstonins, lipopeptides produced by the plant pathogenic bacteria Ralstonia
      solanacearum, interfere with germination of the plant-pathogenic fungus
      Aspergillus flavus by down-regulating expression of a cryptic biosynthetic gene
      cluster (BGC), named imq. Comparative metabolomic analysis of overexpression
      strains of the transcription factor ImqK revealed imq-dependent production of a
      family of tripeptide-derived alkaloids, the imizoquins. These alkaloids are
      produced via a nonribosomal peptide synthetase- (NRPS-)derived tripeptide and
      contain an unprecedented tricyclic imidazo[2,1-a]isoquinoline ring system. We
      show that the imizoquins serve a protective role against oxidative stress that is
      essential for normal A. flavus germination. Supplementation of purified
      imizoquins restored wildtype germination to a DeltaimqK A. flavus strain and
      protected the fungus from ROS damage. Whereas the bacterial ralstonins retarded
      A. flavus germination and suppressed expression of the imq cluster, the fungal
      imizoquins in turn suppressed growth of R. solanacearum. We suggest such
      reciprocal small-molecule-mediated antagonism is a common feature in microbial
      encounters affecting pathogenicity and survival of the involved species.

PMID- 29182849
TI  - Ion Trapping of Amines in Protozoa: A Novel Removal Mechanism for Micropollutants
      in Activated Sludge.
AB  - To optimize removal of organic micropollutants from the water cycle,
      understanding the processes during activated sludge treatment is essential. In
      this study, we hypothesize that aliphatic amines, which are highly abundant among
      organic micropollutants, are partly removed from the water phase in activated
      sludge through ion trapping in protozoa. In ion trapping, which has been
      extensively investigated in medical research, the neutral species of amine
      containing compounds diffuse through the cell membrane and further into acidic
      vesicles present in eukaryotic cells such as protozoa. There they become trapped
      because diffusion of the positively charged species formed in the acidic vesicles
      is strongly hindered. We tested our hypothesis with two experiments. First, we
      studied the distribution of the fluorescent amine acridine orange in activated
      sludge by confocal fluorescence imaging. We observed intense fluorescence in
      distinct compartments of the protozoa, but not in the bacterial biomass. Second,
      we investigated the distribution of 12 amine-containing and eight control
      micropollutants in both regular activated sludge and sludge where the protozoa
      had been inactivated. In contrast to most control compounds, the amine-containing
      micropollutants displayed a distinctly different behavior in the noninhibited
      sludge compared to the inhibited one: (i) more removal from the liquid phase;
      (ii) deviation from first-order kinetics for the removal from the liquid phase;
      and (iii) higher amounts in the solid phase. These results provide strong
      evidence that ion trapping in protozoa occurs and that it is an important removal
      mechanism for amine-containing micropollutants in batch experiments with
      activated sludge that has so far gone unnoticed. We expect that our findings will
      trigger further investigations on the importance of this process in full-scale
      wastewater treatment systems, including its relevance for accumulation of
      ammonium.

PMID- 29182850
TI  - Solid-Solution Sulfides Derived from Tunable Layered Double Hydroxide
      Precursors/Graphene Aerogel for Pseudocapacitors and Sodium-Ion Batteries.
AB  - Transition-metal sulfides (TMSs) are suggested as promising electrode materials
      for electrochemical pseudocapacitors and lithium- and sodium-ion batteries;
      however, they typically involve mixed composites or conventionally stoichiometric
      TMSs (such as NiCo2S4 and Ni2CoS4). Herein we demonstrate a preparation of solid
      solution sulfide (Ni0.7Co0.3)S2 supported on three-dimensional graphene aerogel
      (3DGA) via a sulfuration of NiCo-layered double hydroxide (NiCo-LDH)
      precursor/3DGA. The electrochemical tests show that the (Ni0.7Co0.3)S2/3DGA
      electrode exhibits a capacitance of 2165 F g-1 at 1 A g-1, 2055 F g-1 at 2 A g-1,
      and 1478 F g-1 at 10 A g-1; preserves 78.5% capacitance retention upon 1000
      cycles for pseudocapacitors; and in particular, possesses a relatively high
      charge capacity of 388.7 mA h g-1 after 50 cycles at 100 mA g-1 as anode
      nanomaterials for sodium-ion batteries. Furthermore, the electrochemical
      performances are readily tuned by varying the cationic type of the tunable LDH
      precursors to prepare different solid-solution sulfides, such as
      (Ni0.7Fe0.3)S2/3DGA and (Co0.7Fe0.3)S2/3DGA. Our results show that engineering
      LDH precursors can offer an alternative for preparing diverse transition-metal
      sulfides for energy storage.

PMID- 29182851
TI  - Valley Polarization of Trions and Magnetoresistance in Heterostructures of MoS2
      and Yttrium Iron Garnet.
AB  - Manipulation of spin degree of freedom (DOF) of electrons is the fundamental
      aspect of spintronic and valleytronic devices. Two-dimensional transition metal
      dichalcogenides (2D TMDCs) exhibit an emerging valley pseudospin, in which spin
      up (-down) electrons are distributed in a +K (-K) valley. This valley
      polarization gives a DOF for spintronic and valleytronic devices. Recently,
      magnetic exchange interactions between graphene and magnetic insulator yttrium
      iron garnet (YIG) have been exploited. However, the physics of 2D TMDCs with YIG
      have not been shown before. Here we demonstrate strong many-body effects in a
      heterostructure geometry comprising a MoS2 monolayer and YIG. High-order trions
      are directly identified by mapping absorption and photoluminescence at 12 K. The
      electron doping density is up to ~1013 cm-2, resulting in a large splitting of
      ~40 meV between trions and excitons. The trions exhibit a high circular
      polarization of ~80% under optical pumping by circularly polarized light at ~1.96
      eV; it is confirmed experimentally that both phonon scattering and electron-hole
      exchange interaction contribute to the valley depolarization with temperature;
      importantly, a magnetoresistance (MR) behavior in the MoS2 monolayer was
      observed, and a giant MR ratio of ~30% is achieved, which is 1 order of magnitude
      larger than the reported ratio in MoS2/CoFe2O4 heterostructures. Our experimental
      results confirm that the giant MR behaviors are attributed to the interfacial
      spin accumulation due to YIG substrates. Our work provides an insight into spin
      manipulation in a heterostructure of monolayer materials and magnetic substrates.

PMID- 29182852
TI  - Multilayer Graphene-WSe2 Heterostructures for WSe2 Transistors.
AB  - Two-dimensional (2D) materials are drawing growing attention for next-generation
      electronics and optoelectronics owing to its atomic thickness and unique physical
      properties. One of the challenges posed by 2D materials is the large source/drain
      (S/D) series resistance due to their thinness, which may be resolved by
      thickening the source and drain regions. Recently explored lateral graphene-MoS21
      3 and graphene-WS21,4 heterostructures shed light on resolving the mentioned
      issues owing to their superior ohmic contact behaviors. However, recently
      reported field-effect transistors (FETs) based on graphene-TMD heterostructures
      have only shown n-type characteristics. The lack of p-type transistor limits
      their applications in complementary metal-oxide semiconductor electronics. In
      this work, we demonstrate p-type FETs based on graphene-WSe2 lateral
      heterojunctions grown with the scalable CVD technique. Few-layer WSe2 is
      overlapped with the multilayer graphene (MLG) at MLG-WSe2 junctions such that the
      contact resistance is reduced. Importantly, the few-layer WSe2 only forms at the
      junction region while the channel is still maintained as a WSe2 monolayer for
      transistor operation. Furthermore, by imposing doping to graphene S/D, 2 orders
      of magnitude enhancement in Ion/Ioff ratio to ~108 and the unipolar p-type
      characteristics are obtained regardless of the work function of the metal in
      ambient air condition. The MLG is proposed to serve as a 2D version of emerging
      raised source/drain approach in electronics.

PMID- 29182853
TI  - Role of Precursor-Conversion Chemistry in the Crystal-Phase Control of
      Catalytically Grown Colloidal Semiconductor Quantum Wires.
AB  - Crystal-phase control is one of the most challenging problems in nanowire growth.
      We demonstrate that, in the solution-phase catalyzed growth of colloidal cadmium
      telluride (CdTe) quantum wires (QWs), the crystal phase can be controlled by
      manipulating the reaction chemistry of the Cd precursors and tri-n-octylphosphine
      telluride (TOPTe) to favor the production of either a CdTe solute or Te, which
      consequently determines the composition and (liquid or solid) state of the
      BixCdyTez catalyst nanoparticles. Growth of single-phase (e.g., wurtzite) QWs is
      achieved only from solid catalysts (y ? z) that enable the solution-solid-solid
      growth of the QWs, whereas the liquid catalysts (y ~ z) fulfill the solution
      liquid-solid growth of the polytypic QWs. Factors that affect the precursor
      conversion chemistry are systematically accounted for, which are correlated with
      a kinetic study of the composition and state of the catalyst nanoparticles to
      understand the mechanism. This work reveals the role of the precursor-reaction
      chemistry in the crystal-phase control of catalytically grown colloidal QWs,
      opening the possibility of growing phase-pure QWs of other compositions.

PMID- 29182855
TI  - Bacterial Adhesion to Ultrafiltration Membranes: Role of Hydrophilicity, Natural
      Organic Matter, and Cell-Surface Macromolecules.
AB  - Insight into the mechanisms underlying bacterial adhesion is critical to the
      formulation of membrane biofouling control strategies. Using AFM-based single
      cell force spectroscopy, we investigated the interaction between Pseudomonas
      fluorescens, a biofilm-forming bacterium, and polysulfone (PSF) ultrafiltration
      (UF) membranes to unravel the mechanisms underlying early stage membrane
      biofouling. We show that hydrophilic polydopamine (PDA) coatings decrease
      bacterial adhesion forces at short bacterium-membrane contact times. Further, we
      find that adhesion forces are weakened by the presence of natural organic matter
      (NOM) conditioning films, owing to the hydrophilicity of NOM. Investigation of
      the effect of adhesion contact time revealed that PDA coatings are less effective
      at preventing bioadhesion when the contact time is prolonged to 2-5 s, or when
      the membranes are exposed to bacterial suspensions under stirring. These results
      therefore challenge the notion that simple hydrophilic surface coatings are
      effective as a biofouling control strategy. Finally, we present evidence that
      adhesion to the UF membrane surface is mediated by cell-surface macromolecules
      (likely to be outer membrane proteins and pili) which, upon contacting the
      membrane, undergo surface-induced unfolding.

PMID- 29182854
TI  - Identification of a Functionally Unique Family of Penicillin-Binding Proteins.
AB  - Penicillin-binding proteins (PBPs) are enzymes involved in the assembly of the
      bacterial cell wall, a major target for antibiotics. These proteins are
      classified by mass into high-molecular-weight PBPs, which are transpeptidases
      that form peptidoglycan cross-links, and low-molecular-weight PBPs, which are
      typically hydrolases. We report a functionally unique family of low-molecular
      weight PBPs that act as transpeptidases rather than hydrolases, but they do not
      cross-link peptidoglycan. We show that these PBPs can exchange d-amino acids
      bearing chemical tags or affinity handles into peptidoglycan precursors,
      including Lipid II, enabling biochemical studies of proteins involved in cell
      wall assembly. We report that, in two organisms, the PBPs incorporate lysine into
      cellular peptidoglycan and that, further, the PBPs have the unprecedented ability
      to transfer the primary epsilon-amine of lysine to peptidoglycan.

PMID- 29182856
TI  - Direct Observation of Photoinduced Ultrafast Generation of Singlet and Triplet
      Quinone Methides in Aqueous Solutions and Insight into the Roles of Acidic and
      Basic Sites in Quinone Methide Formation.
AB  - Femtosecond time-resolved transient absorption spectroscopy experiments and
      density functional theory computations were done for a mechanistic investigation
      of 3-(1-phenylvinyl)phenol (1) and 3-hydroxybenzophenone (2) in selected
      solvents. Both compounds went through an intersystem crossing (ISC) to form the
      triplet excited states Tpipi* and Tnpi* in acetonitrile but behave differently in
      neutral aqueous solutions, in which a triplet excited state proton transfer
      (ESPT) induced by the ISC process is also proposed for 2 but a singlet ESPT
      without ISC is proposed for 1, leading to the production of the triplet quinone
      methide (QM) and the singlet excited QM species respectively in these two
      systems. The triplet QM then underwent an ISC process to form an unstable ground
      state intermediate which soon returned to its starting material 2. However, the
      singlet excited state QM went through an internal conversion process to the
      ground state QM followed by the formation of its final product in an irreversible
      manner. These differences are thought to be derived from the slow vinyl C-C
      rotation and the moderate basicity of the vinyl C atom in 1 as compared with the
      fast C-O rotation and the greater basicity of the carbonyl O atom of 2 after
      photoexcitation. This can account for the experimental results in the literature
      that the aromatic vinyl compounds undergo efficient singlet excited state
      photochemical reactions while the aromatic carbonyl compounds prefer triplet
      photochemical reactions under aqueous conditions. These results have fundamental
      and significant implications for understanding of the ESPT reactivity in general,
      as well as for the design of molecules for efficient QM formation in aqueous
      media with potential applications in cancer phototherapy.

PMID- 29182857
TI  - Surface Functionalization of Metal-Organic Framework Crystals with Catechol
      Coatings for Enhanced Moisture Tolerance.
AB  - Robust catechol coatings for enhanced moisture tolerance were produced in one
      step by direct reaction of Hong Kong University of Science and Technology (HKUST)
      with synthetic catechols. We ascribe the rapid formation of homogeneous coatings
      around the metal-organic framework particles to the biomimetic catalytic activity
      of Cu(II) dimers in the external surface of the crystals. Use of fluorinated
      catechols results in hydrophobic, permeable coatings that protect HKUST from
      water degradation while retaining close to 100% of its original sorption
      capacity.

PMID- 29182858
TI  - Cell-free DNA: A Neglected Source for Antibiotic Resistance Genes Spreading from
      WWTPs.
AB  - Cell-associated ARGs in wastewater treatment plants (WWTPs) has been concerned,
      however, cell-free ARGs in WWTPs was rarely studied. In this study, the
      abundances of four representative ARGs, sulII, tetC, blaPSE-1, and ermB, in a
      large municipal WWTP were investigated in both cell-associated and cell-free
      fractions. Cell-associated ARGs was the dominant ARGs fraction in the raw
      wastewater. After biological treatment, sludge settling, membrane filtration, and
      disinfection, cell-associated ARGs were substantially reduced, though the ratios
      of ARG/16S rRNA gene were increased with disinfection. Cell-free ARGs persisted
      in the WWTP with a removal of 0.36 log to 2.68 logs, which was much lower than
      the removal of cell-associated ARGs (3.21 logs to 4.14 logs). Therefore, the
      abundance ratio of cell-free ARGs to cell-associated ARGs increased from 0.04
      1.59% to 2.00-1895.08% along the treatment processes. After 25-day-storage, cell
      free ARGs in both biological effluent and disinfection effluent increased by 0.14
      log to 1.99 logs and 0.12 log to 1.77 logs respectively, reflecting the
      persistence and low decay rate of cell-free ARGs in the discharge water.
      Therefore, cell-free ARGs might be a kind of important but previously neglected
      pollutant from WWTPs, which added potential risks to the effluent receiving
      environments.

PMID- 29182859
TI  - High Circular Polarization of Electroluminescence Achieved via Self-Assembly of a
      Light-Emitting Chiral Conjugated Polymer into Multidomain Cholesteric Films.
AB  - We demonstrate a facile route to obtain high and broad-band circular polarization
      of electroluminescence in single-layer polymer OLEDs. As a light-emitting
      material we use a donor-acceptor polyfluorene with enantiomerically pure chiral
      side-chains. We show that upon thermal annealing the polymer self-assembles into
      a multidomain cholesteric film. By varying the thickness of the polymer emitting
      layer, we achieve high levels of circular polarization of electroluminescence (up
      to 40% excess of right-handed polarization), which are the highest reported for
      polymer OLEDs not using chiral dopants or alignment layers. Mueller matrix
      ellipsometry shows strong optical anisotropies in the film, indicating that the
      circular polarization of luminescence arises mainly after the photon has been
      generated, through selective scattering and birefringence correlated in the
      direction of the initial linear polarization of the photon. Our work demonstrates
      that chirally substituted conjugated polymers can combine photonic and
      semiconducting properties in advanced optoelectronic devices.

PMID- 29182861
TI  - Synthesis and Electronic Structures of Heavy Lanthanide Metallocenium Cations.
AB  - The origin of 60 K magnetic hysteresis in the dysprosocenium complex
      [Dy(Cpttt)2][B(C6F5)4] (Cpttt = C5H2tBu3-1,2,4, 1-Dy) remains mysterious, thus we
      envisaged that analysis of a series of [Ln(Cpttt)2]+ (Ln = lanthanide) cations
      could shed light on these properties. Herein we report the synthesis and physical
      characterization of a family of isolated [Ln(Cpttt)2]+ cations (1-Ln; Ln = Gd,
      Ho, Er, Tm, Yb, Lu), synthesized by halide abstraction of [Ln(Cpttt)2(Cl)] (2-Ln;
      Ln = Gd, Ho, Er, Tm, Yb, Lu). Complexes within the two families 1-Ln and 2-Ln are
      isostructural and display pseudo-linear and pseudo-trigonal crystal fields,
      respectively. This results in archetypal electronic structures, determined with
      CASSCF-SO calculations and confirmed with SQUID magnetometry and EPR
      spectroscopy, showing easy-axis or easy-plane magnetic anisotropy depending on
      the choice of Ln ion. Study of their magnetic relaxation dynamics reveals that 1
      Ho also exhibits an anomalously low Raman exponent similar to 1-Dy, both being
      distinct from the larger and more regular Raman exponents for 2-Dy, 2-Er, and 2
      Yb. This suggests that low Raman exponents arise from the unique spin-phonon
      coupling of isolated [Ln(Cpttt)2]+ cations. Crucially, this highlights a direct
      connection between ligand coordination modes and spin-phonon coupling, and
      therefore we propose that the exclusive presence of multihapto ligands in 1-Dy is
      the origin of its remarkable magnetic properties. Controlling the spin-phonon
      coupling through ligand design thus appears vital for realizing the next
      generation of high-temperature single-molecule magnets.

PMID- 29182860
TI  - Investigating Pharmacological Targeting of G-Quadruplexes in the Human Malaria
      Parasite.
AB  - The unique occurrence of G-quadruplexes in the AT-rich genome of human malaria
      parasite Plasmodium falciparum provides hints about their critical roles in
      parasite survival, pathogenesis, and host immune evasion. An intriguing question
      is whether these noncanonical structures can serve as molecular targets for small
      molecule-based interventions against malaria. In this study, we have investigated
      the pharmacological targeting of G-quadruplexes for parasite inhibition. We
      observed that bisquinolinium derivatives of 1,8-naphthyridine and pyridine
      affected the stability and molecular recognition properties of G-quadruplexes in
      telomeric and subtelomeric regions in P. falciparum. Parasite inhibition and
      cytotoxicity assays revealed that these ligands effectively inhibit parasite
      growth with minimal toxic effects in human cells. G-quadruplex interacting
      ligands caused degeneration and shortening of parasite telomeres. Ligand-induced
      perturbations in telomere homeostasis also affected transcriptional state of the
      subtelomeric region harboring antigenic variation genes. Taken together, our
      results suggest that quadruplex-ligand interaction disturbs
      telomeric/subtelomeric chromatin organization and induces DNA damage that
      consequently leads to parasite death. Our findings also draw attention to the
      striking differences in telomere dynamics in the protozoan parasite and human
      host that can be exploited for selective targeting of the telomeric quadruplex of
      the parasite as a potential antimalarial strategy.

PMID- 29182862
TI  - Inhibition of Mammalian 15-Lipoxygenase by Three Ebselen-like Drugs. A QM/MM and
      MM/PBSA Comparative Study.
AB  - Ebselen is a potent competitive inhibitor of the active form of rabbit 15
      lipoxygenase, an enzyme involved in many inflammatory diseases. Light-induced Z
      to-E isomerization of the ebselen-like 2-(3-benzylidene)-3-oxo-2,3
      dihydrobenzo[b]thiophene-7-carboxylic acid methyl ester (BODTCM) molecule was
      used to convert the weak (Z)-BOTDCM inhibitor into the (E)-isomer with much
      higher inhibitory capacity. In this study, the binding modes of ebselen, (E)
      BOTDCM and (Z)-BOTDCM, have been analyzed to provide molecular insights on the
      inhibitory potency of ebselen and on the geometric-isomer specificity of (E)- and
      (Z)-BOTDCM inhibitors. The inhibitor-enzyme structures obtained from docking and
      molecular dynamics simulations as well as from QM/MM calculations show that the
      inhibitor molecules are not coordinated to the nonheme iron in the active site.
      Thermal motion allows ebselen and (E)-BOTDCM to visit a wide range of the
      configurational space competing with the polyunsaturated fatty acid for binding
      at the active site. Both molecules present similar MM/PBSA binding free energies.
      The energy penalty for the bigger geometric deformation undergone by (E)-BODTCM
      would explain its lower inhibitor potency. The (Z)-isomer is the weakest
      inhibitor because thermal motion moves it to a region very far from the first
      coordination sphere of Fe, where it could not compete with the fatty acid
      substrate.

PMID- 29182863
TI  - The Atmospheric Oxidation of HONO by OH, Cl, and ClO Radicals.
AB  - The atmospheric oxidation of nitrous acid by hydroxyl radical, chlorine atom, and
      chlorine monoxide radical was investigated with high-level theoretical methods.
      Nitrous acid has two conformers (cis and trans), and we found a reaction path for
      the oxidation of each of these conformers with the radicals considered. In all
      cases, the oxidation of the cis conformer is much more favorable than the
      oxidation of the trans conformer. Interestingly all transition states in these
      oxidation processes follow a proton-coupled electron-transfer mechanism. Our
      computed rate constant at 298 K for the reaction of cis-HONO + .OH is 4.83 * 10
      12 cm3 molecule-1 s-1, in excellent agreement with their experimental values
      (4.85 * 10-12 and 6.48 * 10-12 cm3 molecule-1 s-1). For the trans-HONO + .OH
      reaction our calculated rate constant at 298 K is 9.05 * 10-18 cm3 molecule-1 s
      1, and we computed an effective rate constant for the oxidation of the whole
      nitrous acid by hydroxyl radical of 1.81 * 10-12 cm3 molecule-1 s-1. For the
      oxidation of nitrous acid by chlorine atom we predict greater rate constants
      (7.38 * 10-11, 3.33 * 10-15, and 2.76 * 10-11 cm3 molecule-1 s-1, for the cis and
      trans conformers and for the whole HONO), these results suggesting that this
      reaction should contribute to the tropospheric oxidation of nitrous acid,
      especially in marine boundary areas, and to the formation of tropospheric ozone.
      For the oxidation of nitrous acid by chlorine monoxide we predict rate constants
      roughly 6 orders of magnitude smaller than the oxidation by chlorine atom, and
      therefore we consider that this process should play a minor role in the
      troposphere.

PMID- 29182864
TI  - Electronic Properties and Electroluminescent OLED Performance of Panchromatic
      Emissive N-Aryl-2,3-naphthalimides.
AB  - This report investigates the excited-state properties of a series of N-aryl-2,3
      naphthalimides along with their fabrication into OLEDs and electroluminescence
      measurements. The N-aryl-2,3-NIs substituted specifically with chloro, fluoro,
      and methoxy substituents were chosen because of their unique propensity to
      display two emission bands or panchromatic fluorescence. Using the Lippert-Mataga
      analysis along with TD-DFT calculations, the excited states were determined to be
      n,pi* and pi,pi*. The TD-DFT calculations on the geometries of the excited states
      indicate that the excited state shows a planar structure. The origin of both the
      short wavelength (SW) and long wavelength (LW) emission were correlated to
      specific geometries such that the SW emission originates from an "angled"
      structure in the excited state, and LW emission originates from an excited state
      of coplanar structure. All of the dyes investigated readily formed good films
      under ultrahigh vacuum deposition. The molecular energy levels of these compounds
      (HOMO and LUMO) were measured with cyclic voltammetry. Band gaps were also
      measured in both electrochemical and optical methods and indicate that the HOMOs
      of these fluorophores matched well with the anode (ITO work function), and their
      LUMOs matched well with the cathode (LiF/Al). To compare photoluminescence of the
      four dyes with their potential electroluminescence, three OLED devices were
      designed and fabricated. The electroluminescent spectra of these devices indicate
      that the panchromatic fluorescence, observed in solution, shifts toward the red
      in the solid-state. A plausible explanation appears to stem from an inability to
      inject electrons to the higher LUMO+1 orbitals; a process observed in the
      solution phase. Hence, the short wavelength fluorescence peak, a key component to
      panchromatic luminescence disappears in the OLED device. The observed EL spectrum
      from these smaller heteroatomic architectures is on par if not more broadly
      emissive than rubrene (5,6,11,12-tetraphenyltetracene), a red-colored C42H28
      polycyclic aromatic hydrocarbon, that displays an orange-color EL.

PMID- 29182865
TI  - Cobalt- and Silver-Promoted Methylenecyclopropane Rearrangements.
AB  - The rate of the methylenecyclopropane rearrangement is enhanced by an alkyne
      Co2(CO)6 complex bonded to the para position of a benzene ring. This is explained
      by a stabilizing effect on the transition state leading to the biradical
      intermediate. Computational studies indicate that the benzylic-type biradical
      intermediate is stabilized by a delocalization mechanism, where spin is
      delocalized onto the two cobalt atoms. Silver cation also enhances the rate of
      the methylenecyclopropane rearrangement. Computational studies suggest that
      silver cation can also stabilize a benzylic radical by spin delocalization
      involving silver. In the case of the silver-promoted reactions, the rate
      enhancements in a series of aryl-substituted methylenecyclopropanes correlate
      with sigma+ values. The question remains open as to whether the silver-catalyzed
      methylenecyclopropane rearrangement proceeds via an argento-stabilized biradical
      or whether the reaction involves an argento-substituted allylic cation.

PMID- 29182866
TI  - Clickable Cubosomes for Antibody-Free Drug Targeting and Imaging Applications.
AB  - The combination of copper-free click chemistry with metabolic labeling offers new
      opportunities in drug delivery. The objective of this study was to determine
      whether cubosomes functionalized with azide or dibenzocyclooctyne (DBCO) groups
      are able to undergo copper-free click chemistry with a strained cyclooctyne or
      azide, respectively. Phytantriol-based cubosomes were functionalized using
      phospholipids bearing an azide or DBCO group. The modified cubosome dispersions
      were characterized using dynamic light scattering, cryo-TEM, and small-angle X
      ray scattering. The efficiency of "clickability" was assessed by reacting the
      cubosomes with a complementary dye and determining bound and unbound dye via size
      exclusion chromatography. The clickable cubosomes reacted specifically and
      efficiently with a click-Cy5 dye with minor changes to the size, shape, and
      structure of the cubosomes. This indicates that cubosomes can retain their unique
      internal structure while participating in copper-free click chemistry. This proof
      of concept study paves the way for the use of copper-free click chemistry and
      metabolic labeling with cubosomes for targeted drug delivery and imaging.

PMID- 29182867
TI  - Sustained Bauxite Residue Rehabilitation with Gypsum and Organic Matter 16 years
      after Initial Treatment.
AB  - Bauxite residue is a high volume byproduct of alumina manufacture which is
      commonly disposed of in purpose-built bauxite residue disposal areas (BRDAs).
      Natural waters interacting with bauxite residue are characteristically highly
      alkaline, and have elevated concentrations of Na, Al, and other trace metals.
      Rehabilitation of BRDAs is therefore often costly and resource/infrastructure
      intensive. Data is presented from three neighboring plots of bauxite residue that
      was deposited 20 years ago. One plot was amended 16 years ago with process sand,
      organic matter, gypsum, and seeded (fully treated), another plot was amended 16
      years ago with process sand, organic matter, and seeded (partially treated), and
      a third plot was left untreated. These surface treatments lower alkalinity and
      salinity, and thus produce a substrate more suitable for biological colonisation
      from seeding. The reduction of pH leads to much lower Al, V, and As mobility in
      the actively treated residue and the beneficial effects of treatment extend
      passively 20-30 cm below the depth of the original amendment. These positive
      rehabilitation effects are maintained after 2 decades due to the presence of an
      active and resilient biological community. This treatment may provide a lower
      cost solution to BRDA end of use closure plans and orphaned BRDA rehabilitation.

PMID- 29182868
TI  - Jacob's Ladder as Sketched by Escher: Assessing the Performance of Broadly Used
      Density Functionals on Transition Metal Surface Properties.
AB  - The present work surveys the performance of various widely used density
      functional theory exchange-correlation (xc) functionals in describing observable
      surface properties of a total of 27 transition metals with face-centered cubic
      (fcc), body-centered cubic (bcc), or hexagonal close-packed (hcp)
      crystallographic structures. A total of 81 low Miller index surfaces were
      considered employing slab models. Exemplary xc functionals within the three first
      rungs of Jacob's ladder were considered, including the Vosko-Wilk-Nusair xc
      functional within the local density approximation, the Perdew-Burke-Ernzerhof
      (PBE) functional within the generalized gradient approximation (GGA), and the Tao
      Perdew-Staroverov-Scuseria functional as a meta-GGA functional. Hybrids were
      excluded in the survey because they are known to fail in properly describing
      metallic systems. In addition, two variants of PBE were considered, PBE adapted
      for solids (PBEsol) and revised PBE (RPBE), aimed at improving adsorption
      energies. Interlayer atomic distances, surface energies, and surface work
      functions were chosen as the scrutinized properties. A comparison with available
      experimental data, including single-crystal and polycrystalline values, shows
      that no xc functional is best at describing all of the surface properties.
      However, in statistical mean terms the PBEsol xc functional is advised, while PBE
      is recommended when considering both bulk and surface properties. On the basis of
      the present results, a discussion of adapting GGA functionals to the treatment of
      metallic surfaces in an alternative way to meta-GGA or hybrids is provided.

PMID- 29182869
TI  - Effects of Chloride and Sulfate Salts on the Inhibition or Promotion of Sucrose
      Crystallization in Initially Amorphous Sucrose-Salt Blends.
AB  - The effects of salts on the stability of amorphous sucrose and its
      crystallization in different environments were investigated. Chloride (LiCl,
      NaCl, KCl, MgCl2, CaCl2, CuCl2, FeCl2, FeCl3, and AlCl3) and sulfate salts with
      the same cations (Na2SO4, K2SO4, MgSO4, CuSO4, Fe(II)SO4, and Fe(III)SO4) were
      studied. Samples (sucrose controls and sucrose:salt 1:0.1 molar ratios) were
      lyophilized, stored in controlled temperature and relative humidity (RH)
      conditions, and monitored for one month using X-ray diffraction. Samples were
      also analyzed by differential scanning calorimetry, microscopy, and moisture
      sorption techniques. All lyophiles were initially amorphous, but during storage
      the presence of a salt had a variable impact on sucrose crystallization. While
      all samples remained amorphous when stored at 11 and 23% RH at 25  degrees C,
      increasing the RH to 33 and 40% RH resulted in variations in crystallization
      onset times. The recrystallization time generally followed the order monovalent
      cations < sucrose < divalent cations < trivalent cations. The presence of a salt
      typically increased water sorption as compared to sucrose alone when stored at
      the same RH; however, anticrystallization effects were observed for sucrose
      combined with salts containing di- and trivalent cations in spite of the
      increased water content. The cation valency and hydration number played a major
      role in dictating the impact of the added salt on sucrose crystallization.

PMID- 29182870
TI  - Catalyst-Controlled Diastereoselective Synthesis of Cyclic Amines via C-H
      Functionalization.
AB  - Reliable regio- and stereochemical techniques applicable to nonactivated
      aliphatic systems remain largely elusive due to the challenges of discriminating
      between multiple, relatively strong sp3 C-H bonds whose chemical behavior often
      differ only subtly. Nevertheless, approaches that employ directing groups and/or
      auxiliaries have emerged, but impose practical restrictions, especially in
      complex molecule synthesis. This report describes a catalyst-controlled regio-
      and diastereoselective synthesis of N-unprotected pyrrolidines via dirhodium
      catalyzed intramolecular nitrene insertion into sp3 C-H bonds. The reaction
      proceeds at rt without external oxidants, nitrene stabilizing groups, or
      directing functionality. The insights that emerged from the
      conformational/stereoselectivity relationships (CSR) between catalysts and
      substrates provide a framework for rational catalyst design that can accommodate
      a broader range of aliphatic C-H chemistry.

PMID- 29182871
TI  - Contaminant Gradients in Trees: Directional Tree Coring Reveals Boundaries of
      Soil and Soil-Gas Contamination with Potential Applications in Vapor Intrusion
      Assessment.
AB  - Contaminated sites pose ecological and human-health risks through exposure to
      contaminated soil and groundwater. Whereas we can readily locate, monitor, and
      track contaminants in groundwater, it is harder to perform these tasks in the
      vadose zone. In this study, tree-core samples were collected at a Superfund site
      to determine if the sample-collection location around a particular tree could
      reveal the subsurface location, or direction, of soil and soil-gas contaminant
      plumes. Contaminant-centroid vectors were calculated from tree-core data to
      reveal contaminant distributions in directional tree samples at a higher
      resolution, and vectors were correlated with soil-gas characterization collected
      using conventional methods. Results clearly demonstrated that directional tree
      coring around tree trunks can indicate gradients in soil and soil-gas contaminant
      plumes, and the strength of the correlations were directly proportionate to the
      magnitude of tree-core concentration gradients (spearman's coefficient of -0.61
      and -0.55 in soil and tree-core gradients, respectively). Linear regression
      indicates agreement between the concentration-centroid vectors is significantly
      affected by in planta and soil concentration gradients and when concentration
      centroids in soil are closer to trees. Given the existing link between soil-gas
      and vapor intrusion, this study also indicates that directional tree coring might
      be applicable in vapor intrusion assessment.

PMID- 29182872
TI  - Isocanthine Synthesis via Rh(III)-Catalyzed Intramolecular C-H Functionalization.
AB  - An efficient synthesis of substituted isocanthines has been achieved using an
      intramolecular Rh(III)-catalyzed C-H functionalization of alkyne-tethered indoles
      in the presence of catalytic
      tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate
      and stoichiometric copper(II) acetate. This isocanthine synthesis tolerates a
      variety of electronically diverse 5- or 6-substituted indoles with N-tethered
      alkyne coupling partners and can also be extended to pyrrole derivatives for the
      synthesis of annulated 5-azaindoles.

PMID- 29182873
TI  - Mechanical Unfolding of Macromolecules Coupled to Bond Dissociation.
AB  - Single-molecule force spectroscopy has become a powerful tool to investigate
      molecular mechanisms in biophysics and materials science. In particular, the new
      field of polymer mechanochemistry has emerged to study how tension may induce
      chemical reactions in a macromolecule. A rich example is the mechanical unfolding
      of the metalloprotein rubredoxin coupled to dissociation of iron-sulfur bonds
      that has recently been studied in detail by atomic force microscopy. Here, we
      present a simple molecular model composed of a classical all-atom force field
      description, implicit solvation, and steered molecular dynamics simulation to
      describe the mechanical properties and mechanism of forced unfolding coupled to
      covalent bond dissociation of macromolecules. We apply this model and test it
      extensively to simulate forced rubredoxin unfolding, and we dissect the
      sensitivity of the calculated mechanical properties with model parameters. The
      model provides a detailed molecular explanation of experimental observables such
      as force-extension profiles and contour length increments. Changing the points of
      force application along the macromolecule results in different unfolding
      mechanisms, characterized by disruption of hydrogen bonds and secondary protein
      structure, and determines the degree of solvent access to the reactive center. We
      expect that this molecular model will be broadly applicable to simulate
      (bio)polymer mechanochemistry.

PMID- 29182874
TI  - Revisiting Nitrogen Species in Covalent Triazine Frameworks.
AB  - Covalent triazine frameworks (CTFs) are porous organic materials promising for
      applications in catalysis and separation due to their high stability, adjustable
      porosity, and intrinsic nitrogen functionalities. CTFs are prepared by
      ionothermal trimerization of aromatic nitriles; however, multiple side reactions
      also occur under synthesis conditions, and their influence on the material
      properties is still poorly described. Here we report the systematic
      characterization of nitrogen in CTFs using X-ray photoelectron spectroscopy. With
      the use of model compounds, we could distinguish several types of nitrogen
      species. By combining these data with textural properties, we unravel the
      influence that the reaction temperature, the catalyst, and the monomer structure
      and composition have on the properties of the resulting CTF materials.

PMID- 29182875
TI  - Synthesis, Characterization, and Application of Partially Blocked Amine
      Functionalized Magnetic Nanoparticles.
AB  - In this study, a novel technique was introduced for selective surface
      modification of amine-functionalized magnetic nanoparticles. The method was based
      on alignment of magnetic nanoparticles in an external magnetic field, which
      resulted in formation of chain-like assemblies in diluted suspensions. The
      aligned chains were then modified on the surface via reaction of isocyanate
      species with the particle functionalities. Finally, after removal from the
      reactor medium, particles with segmented distribution of surface functionalities
      were achieved. We named these partially blocked amine-functionalized magnetic
      nanoparticles as "Saturn" nanoparticles. Application of the particles in
      fabrication of magnetic assemblies was successfully demonstrated. Using methylene
      diphenyl diisocyanate (MDI) as the bridging agent, structures in different forms
      such as chains and filaments were produced by the Saturn particles and compared
      with cross-linked structures of the unmodified amine-functionalized particles. It
      is expected that this novel nanoparticle with its unique structure will have
      great potential in assembly fabrication with a variety of applications in
      biomedical fields.

PMID- 29182876
TI  - Solid-State Hydrogen-Deuterium Exchange Mass Spectrometry: Correlation of
      Deuterium Uptake and Long-Term Stability of Lyophilized Monoclonal Antibody
      Formulations.
AB  - Solid state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX
      MS) has been used to assess protein conformation and matrix interactions in
      lyophilized solids. ssHDX-MS metrics have been previously correlated to the
      formation of aggregates of lyophilized myoglobin on storage. Here, ssHDX-MS was
      applied to lyophilized monoclonal antibody (mAb) formulations and correlated to
      their long-term stability. After exposing lyophilized samples to D2O(g), the
      amount of deuterium incorporated at various time points was determined by mass
      spectrometry for four different lyophilized mAb formulations. Hydrogen-deuterium
      exchange data were then correlated with mAb aggregation and chemical degradation,
      which was obtained in stability studies of >2.5 years. Deuterium uptake on ssHDX
      MS of four lyophilized mAb formulations determined at the initial time point
      prior to storage in the dry state was directly and strongly correlated with the
      extent of aggregation and chemical degradation during storage. Other measures of
      physical and chemical properties of the solids were weakly or poorly correlated
      with stability. The data demonstrate, for the first time, that ssHDX-MS results
      are highly correlated with the stability of lyophilized mAb formulations. The
      findings thus suggest that ssHDX-MS can be used as an early read-out of
      differences in long-term stability between formulations helping to accelerate
      formulation screening and selection.

PMID- 29182877
TI  - Doping Lanthanide into Perovskite Nanocrystals: Highly Improved and Expanded
      Optical Properties.
AB  - Cesium lead halide (CsPbX3) perovskite nanocrystals (NCs) have demonstrated
      extremely excellent optical properties and great application potentials in
      various optoelectronic devices. However, because of the anion exchange, it is
      difficult to achieve white-light and multicolor emission for practical
      applications. Herein, we present the successful doping of various lanthanide ions
      (Ce3+, Sm3+, Eu3+, Tb3+, Dy3+, Er3+, and Yb3+) into the lattices of CsPbCl3
      perovskite NCs through a modified hot-injection method. For the lanthanide ions
      doped perovskite NCs, high photoluminescence quantum yield (QY) and stable and
      widely tunable multicolor emissions spanning from visible to near-infrared (NIR)
      regions are successfully obtained. This work indicates that the doped perovskite
      NCs will inherit most of the unique optical properties of lanthanide ions and
      deliver them to the perovskite NC host, thus endowing the family of perovskite
      materials with excellent optical, electric, or magnetic properties.

PMID- 29182878
TI  - Synthesis, Polymerization, and Assembly of Nanosilica Particles below the
      Isoelectric Point.
AB  - The particle growth of silica below the isoelectric point plays a key role in oil
      well cements, production of silica gels and production of nanosilica by
      dissolving silicates. In this article, we study the particle growth of silica
      below the isoelectric point using olivine, a silicate mineral, and sodium
      silicate solutions as silica sources in acid, where the particle size, soluble
      silica concentration, specific surface area and gelling time were measured. The
      size of the primary particles detected by laser light scattering is 3 nm in the
      experiments with sodium silicate solutions. These particles grow then by
      aggregation forming linear chains which in time will start to branch. The
      particle growth follows a quadratic polynomial function and particles as large as
      100 and 500 nm are detected in the final stages of experiments using sodium
      silica solutions and olivine, respectively. Based on these findings, a
      comprehensive model describing the silica particle development below the
      isoelectric point is proposed. This model gives fundamental information about the
      growth mechanism and the properties of silica (e.g., particle size of the primary
      particles, size of the aggregates) at the different growth stages.

PMID- 29182879
TI  - Surfactant-Solvent Interaction Effects on the Micellization of Cationic
      Surfactants in a Carboxylic Acid-Based Deep Eutectic Solvent.
AB  - Deep eutectic solvents have been demonstrated to support amphiphile self
      assembly, providing potential alternatives as structure-directing agents in the
      synthesis of nanostructures, and drug delivery. Here we have expanded on this
      recent research to investigate the self-assembly of alkyltrimethylammonium
      bromide surfactants in choline chloride:malonic acid deep eutectic solvent and
      mixtures of the solvent with water. Surface tension and small-angle neutron
      scattering were used to determine the behavior of the amphiphiles. Surfactants
      were found to remain active in the solvent, and surface tension measurements
      revealed changes in the behavior of the surfactants with different levels of
      hydration. Small-angle neutron scattering shows that in this solvent the micelle
      shape depends on the surfactant chain length, varying from globular micelles
      (aspect ratio ~2) for short chain surfactants to elongated micelles (aspect ratio
      ~14) for long chain surfactants even at low surfactant concentration. We suggest
      that the formation of elongated micelles can be explained through the interaction
      of the solvent with the surfactant headgroup, since ion-ion interactions between
      surfactant headgroups and solvent may modify the morphology of the micelles. The
      presence of water in the deep eutectic solvents promotes an increase in the
      charge density at the micelle interface and therefore the formation of less
      elongated, globular micelles.

PMID- 29182880
TI  - Porous-Shell Vanadium Nitride Nanobubbles with Ultrahigh Areal Sulfur Loading for
      High-Capacity and Long-Life Lithium-Sulfur Batteries.
AB  - Lithium-sulfur (Li-S) batteries hold great promise for the applications of high
      energy density storage. However, the performances of Li-S batteries are
      restricted by the low electrical conductivity of sulfur and shuttle effect of
      intermediate polysulfides. Moreover, the areal loading weights of sulfur in
      previous studies are usually low (around 1-3 mg cm-2) and thus cannot fulfill the
      requirement for practical deployment. Herein, we report that porous-shell
      vanadium nitride nanobubbles (VN-NBs) can serve as an efficient sulfur host in Li
      S batteries, exhibiting remarkable electrochemical performances even with
      ultrahigh areal sulfur loading weights (5.4-6.8 mg cm-2). The large inner space
      of VN-NBs can afford a high sulfur content and accommodate the volume expansion,
      and the high electrical conductivity of VN-NBs ensures the effective utilization
      and fast redox kinetics of polysulfides. Moreover, VN-NBs present strong chemical
      affinity/adsorption with polysulfides and thus can efficiently suppress the
      shuttle effect via both capillary confinement and chemical binding, and promote
      the fast conversion of polysulfides. Benefiting from the above merits, the Li-S
      batteries based on sulfur-filled VN-NBs cathodes with 5.4 mg cm-2 sulfur exhibit
      impressively high areal/specific capacity (5.81 mAh cm-2), superior rate
      capability (632 mAh g-1 at 5.0 C), and long cycling stability.

PMID- 29182881
TI  - Highly Fluorescent Silicon Nanocrystals Stabilized in Water Using Quatsomes.
AB  - Fluorescent silicon (Si) nanocrystals (2.8 nm diameter) were incorporated into
      surfactant assemblies of cetyltrimethylammonium bromide (CTAB) and cholesterol,
      called quatsomes. In water, the quatsome-Si nanocrystal assemblies remain
      fluorescent and well-dispersed for weeks. In contrast to Si nanocrystals,
      alkanethiol-capped gold (Au) nanocrystals do not form stable dispersions in water
      with quatsomes. Cryogenic transmission electron microscopy (cryo-TEM) confirmed
      that the Si nanocrystal-quatsome structures do not change over the course of
      several weeks. The long-term stability of the Si nanocrystal-quatsome assemblies,
      their fluorescence, and biocompatibility makes them attractive candidates for
      medical applications.

PMID- 29182882
TI  - When no news is bad news: communication failures and the hidden assumptions that
      threaten safety.

PMID- 29182883
TI  - Clinical Experience with SERPINA1 DNA Sequencing to Detect Alpha-1 Antitrypsin
      Deficiency.

PMID- 29182884
TI  - Four Lessons Learned From School Nurses in New Jersey About Building a Culture of
      Health.
AB  - Building a Culture of Health will give all members of our society the opportunity
      to lead healthier lives. To achieve this aim, more stakeholders in the community
      residents, elected officials, community-based nonprofits, law enforcement, and
      schools-need to be engaged in addressing the health challenges in our
      communities. Moreover, all community stakeholders have to think and act
      "upstream" by addressing the social determinants of health in their communities.
      Discussed in this article are some of the lessons that are being learned from the
      "upstream" actions of school nurses in New Jersey about building a Culture of
      Health.

PMID- 29182885
TI  - Unlocking Data Collection: Practical Tips for School Nurses.
AB  - School nurses contend with a variety of challenges related to collecting and
      using their own data. Seemingly small steps can be taken to overcome these
      challenges, which will result in significant improvements in data collection and
      use. Improving the quality of data collection assists school nurses to identify
      and define practice issues and guide implementation of evidence-based practice
      within their schools and districts. This article provides school nurses with
      practical steps to collect and use school or district specific health data.

PMID- 29182886
TI  - School Nurses on the Front Lines of Medicine: Take a BREATH: The Approach to a
      Student With Respiratory Distress.
AB  - Students presenting with varying degrees of respiratory symptoms and distress
      occur commonly in the school setting. It is important to develop a differential
      diagnosis for respiratory distress, to initiate stabilization of the student with
      life-threatening symptoms, and to triage these students to an appropriate level
      of care (back to the classroom, home with their guardian with follow up at their
      primary health care provider's office, or directly to the closest emergency
      department via Emergency Medical Services). This article describes the initial
      assessment and management of a student presenting with respiratory distress.

PMID- 29182887
TI  - Predicting Asthmatic Responses to Inhaled Allergen Using an Unbiased
      Transcriptomics Approach.

PMID- 29182889
TI  - Learning Healthcare Systems Will Protect Patients from Unscientific Practice
      Variation.

PMID- 29182888
TI  - Psychometric Assessment and Precision Remodeling of the Iowa Infant Feeding
      Attitude Scale to Improve Clinical Use and Efficacy Among Prenatal Women in
      Canada.
AB  - BACKGROUND: The 17-item Iowa Infant Feeding Attitude Scale (IIFAS) has been
      widely used to assess maternal attitudes toward infant feeding and to predict
      breastfeeding intention. The IIFAS has been validated among prenatal women
      located in Newfoundland and Labrador in Canada, although its length may prove
      challenging to complete in a clinical setting. Research aim: The authors aimed to
      reduce the number of items from the original 17-item IIFAS scale while
      maintaining reliability and validity. METHODS: A nonexperimental cross-sectional
      design was used among 1,283 women in their third trimester residing in
      Newfoundland and Labrador. Data were collected from August 2011 to June 2016. An
      exploratory factor analysis using principal component analysis was performed to
      explore the underlying structure of the IIFAS. The internal consistency of both
      the 17-item and reduced version was assessed using Cronbach's alpha and item
      total correlation. The area under the curve and linear regression model were used
      to assess predictive validity of intention to breastfeed. RESULTS: Our findings
      revealed that a 13-item IIFAS (Cronbach's alpha = .870) had relatively similar
      internal consistency to the original IIFAS (Cronbach's alpha = .868). Three
      themes were extracted from the factor analysis, resulting in the removal of four
      items. The reduced scale demonstrated an excellent ability to predict
      breastfeeding intention (area under the curve = 0.914). CONCLUSION: The reduced
      13-item version of the IIFAS is a psychometrically sound instrument that
      maintains its accuracy and validity when measuring maternal feeding attitudes
      during pregnancy and can be more time efficient in clinical settings compared
      with the 17-item IIFAS.

PMID- 29182890
TI  - Cystic Fibrosis Survival Gap Closing between the United States and Canada. Don't
      Leave Anyone Behind!

PMID- 29182891
TI  - Accelerating Research Collaborations Between Academia and Federally Qualified
      Health Centers: Suggestions Shaped by History.

PMID- 29182892
TI  - Diaphragm-Protective Mechanical Ventilation to Improve Outcomes in ICU Patients?

PMID- 29182894
TI  - Evaluating the Evidence for More Frequent Than Annual HIV Screening of Gay,
      Bisexual, and Other Men Who Have Sex With Men in the United States: Results From
      a Systematic Review and CDC Expert Consultation.
AB  - The Centers for Disease Control and Prevention (CDC) recommended in 2006 that
      sexually active gay, bisexual, and other men who have sex with men (MSM) be
      screened for human immunodeficiency virus (HIV) at least annually. A workgroup
      comprising CDC and external experts conducted a systematic review of the
      literature, including benefits, harms, acceptability, and feasibility of annual
      versus more frequent screening among MSM, to determine whether evidence was
      sufficient to change the current recommendation. Four consultations with managers
      of public and nonprofit HIV testing programs, clinics, and mathematical modeling
      experts were conducted to provide input on the programmatic and scientific
      evidence. Mathematical models predicted that more frequent than annual screening
      of MSM could prevent some new HIV infections and would be more cost-effective
      than annual screening, but this evidence was considered insufficient due to study
      design. Evidence supports CDC's current recommendation that sexually active MSM
      be screened at least annually. However, some MSM might benefit from more frequent
      screening. Future research should evaluate which MSM subpopulations would benefit
      most from more frequent HIV screening.

PMID- 29182895
TI  - Efficacy of downhill running training for improving muscular and aerobic
      performances.
AB  - This study investigated effects of downhill (DR) versus level (LR) running
      training on various muscular and aerobic performances. Eighteen healthy young
      males conducted either DR (DR group (DRG), n = 10: -10% slope) or LR (LR group
      (LRG), n = 8) training at a target heart rate (HR) associated with lactate
      threshold (LT) for 20 min.session-1, 3 sessions.week-1, for 5 weeks. Before and
      after the interventions, the following variables were measured: knee extension
      torque (-150, -30, 0, 30, 150 degrees .s-1), leg extension power (simultaneous
      hip and knee extension: 0.8 m.s-1), squat and countermovement jump height,
      rebound jump index (jump height.contact time-1), 20-m linear sprint and change-of
      direction (Pro-agility and V-cut tests) time, and aerobic capacity (maximal
      oxygen uptake, energy cost at LT, and velocity at maximal oxygen uptake and LT)
      on a level surface. Throughout the training sessions, HR during running did not
      differ between the groups (DRG: 77.7% +/- 4.6% vs LRG: 76.4% +/- 4.6% of maximal
      HR; average across all sessions), while velocity was significantly higher for DRG
      (14.5 +/- 1.1 vs 12.0 +/- 1.9 km.h-1). After the training, DRG significantly
      improved knee extension torque at all angular velocities (9%-24%) and change-of
      direction time for both tests (2%-3%), with no changes in other parameters. LRG
      significantly improved maximal oxygen uptake (5%), energy cost at LT (3%), and
      velocity at maximal oxygen uptake (7%), without changes in others. These results
      suggest that DR training has a greater potential to improve the knee extension
      strength and change-of-direction ability, but has little effect on the aerobic
      capacity, compared with HR-matched LR training.

PMID- 29182896
TI  - Editorial: Nanotherapeutics for Cancer Imaging and Therapy.

PMID- 29182897
TI  - Archaeology and anatomy.

PMID- 29182898
TI  - Reconnection surgery in adult post-operative short bowel syndrome < 100 cm: is
      colonic continuity sufficient to achieve enteral autonomy without autologous
      gastrointestinal reconstruction? Report from a single center and systematic
      review of literature.
AB  - A systematic bibliographic research concerning patients operated on for SBS was
      performed: inclusion criteria were adult age, reconnection surgery and SBS < 100
      cm. Autologous gastrointestinal reconstruction represented an exclusion criteria.
      The outcomes of interest were the rate of total parenteral nutrition (TPN)
      independence and the length of follow-up (minimum 1 year) after surgery. We
      reviewed our experience from 2003 to 2013 with minimum 1-year follow-up, dealing
      with reconnection surgery in 13 adults affected by < 100 cm SBS after massive
      small bowel resection: autologous gastrointestinal reconstruction was not
      feasible. Three (out of 5168 screened papers) non randomized controlled trials
      with 116 adult patients were analysed showing weaning from TPN (40%, 50% and 90%
      respectively) after reconnection surgery without autologous gastrointestinal
      reconstruction. Among our 13 adults, mean age was 54.1 years (53.8 % ASA III):
      69.2 % had a high stomal output (> 500 cc/day) and TPN dependence was 100%. We
      performed a jejuno-colonic anastomosis (SBS type II) in 53.8%, in 46.1% of cases
      without ileo-cecal valve, leaving a mean residual small bowel length of 75.7 cm.
      In-hospital mortality was 0%. After a minimum period of 1 year of intestinal
      rehabilitation, all our patients (100%) went back to oral intake and 69.2% were
      off TPN (9 patients). No one was listed for transplantation. A residual small
      bowel length of minimum 75 cm, even if reconnected to part of the colon, seems
      able to produce a TPN independence without autologous gastrointestinal
      reconstruction after a minimum period of 1 year of intestinal rehabilitation.

PMID- 29182899
TI  - Five year experience of the treatment of squamous cell carcinoma of the anus.
AB  - OBJECTIVES: The best treatment of early stage anal squamous cell carcinoma (SCC)
      is under debated. Wide local excision (WLE) may be considered adequate for stage
      1 anal margin cancer. This study demonstrates our experience in treatment of
      patients with SCC over 5 years. PATIENTS AND METHODS: We conducted a
      retrospective study of patients who had undergone anal screening or anal cancer
      surveillance between October 2010 and 2015 in our department. Each patient
      underwent anal Pap test, HPV test PCR HPV DNA and cytology by Thin Prep. The
      examinations were performed by Proctostation THD(c). Data were collected and
      analysed. RESULTS: We included 25 patients, 16 male (64%) and 9 female (36%).
      Twenty-four patients had SCC and 1 patient had adenocarcinoma. Of this cohort: 10
      underwent chemoradiotherapy (CRT) because T3-4 N1-2 M0, 13 underwent only surgery
      because T1/T2 and 2 patients had CRT and surgery because they already have had
      anal cancer treated in the past with CRT. Seventeen patients (68%) of this
      cohort, including 5 with micro-invasive SCCs, had regular follow-up without
      recurrences. Four patients (17%) died from metastatic disease and 4 patients
      (17%) had recurrent disease. CONCLUSIONS: In this small cohort we demonstrated
      satisfactory results in treatment of SCCs, underlining the effective role of
      surgery in early stages of SCC. Screening program and follow up were fundamental
      to identify early stage and recurrent disease. Also we found the High-resolution
      video-proctoscopy a valid diagnostic tool.

PMID- 29182900
TI  - Laparoscopic sleeve gastrectomy for morbid obesity: role of intraluminal and
      intraperitoneal postoperative drainage.
AB  - BACKGROUND AND AIMS: Bleeding and staple line leak are the most common
      postoperative complications of LSG. To prevent and/or to promptly identify such
      complications, conventional peri-operative protocols imply post-operative gastric
      decompression (NGT) and staple line drain (IAD). Our aim was to evaluate the role
      of naso-gastric tube (NGT) and intra-abdominal drain (IAD) in preventing and/or
      facilitating identification and treatment of post-operative complications after
      sleeve gastrectomy. PATIENTS AND METHODS: A retrospective observational study on
      two consecutive series has been undertaken to evaluate the real utility of
      routine placement of NGT and IAD at the end of a LSG to prevent (primary end
      point), promptly identify (secondary end-point) and manage (tertiary end-point)
      bleeding and staple line leakage. Collected outcome data of all consecutive
      cases, which underwent primary LSG at our Department, were analyzed. The first
      100 consecutive patients (group A) received the standard perioperative protocol
      and the other consecutive 100 (group B) received a fast track protocol (no NGT
      neither IAD). RESULTS: The two groups were not different in their outcome. Two
      bleeding occurred in Group A and were conservatively treated. One abscess
      developed in group B soon after surgery. It was diagnosed by an abdominal CT
      performed because patients presented fever, leucocitosis and tachycardia. It was
      successfully treated by percutaneous ultrasound-guided drainage. One fistula
      occurred in group B after discharge on 30th post-operative day. Fistula was
      suspected based on fever and tachycardia in absence of any abdominal discomfort
      and was confirmed by an abdominal CT. The patient was successfully treated in 40
      days by endoscopic positioning of a gastric tube-prosthesis and percutaneous
      ultrasound-guided drainage of abdominal collection. A third patient in group B
      experienced bleeding suspected due to hemoglobin drop and confirmed by abdominal
      CT. He also was conservatively treated. CONCLUSIONS: In conclusion, placement of
      drains does not facilitate detection of leak, abscess, or bleeding after primary
      LSG.

PMID- 29182902
TI  - A clinical case of perineal invasion from rectal carcinoma.
AB  - We report a case of 62-year old women with skin infiltration in the perineal area
      after anterior rectal resection due to upper rectal cancer. Computed Tomography
      (CT) shows an intense infiltrative aspect of the lesion. The patient had a
      diffuse perineal infiltration predominantly at Levator Ani muscles and adhesions
      to the posterior parts of urinary bladder, uterus, vagina and perineal skin. The
      patient underwent surgery with colostomy to relieve the colonic tract due to
      obstruction and later was treated with chemo-radiation.

PMID- 29182901
TI  - Surgery for post-operative entero-cutaneous fistulas: is bowel resection plus
      primary anastomosis without stoma a safe option to avoid early recurrence? Report
      on 20 cases by a single center and systematic review of the literature.
AB  - BACKGROUND: A review was performed on entero-cutaneous fistula (ECF) repair and
      early recurrence, adding our twenty adult patients (65% had multiple fistulas).
      METHODS: The search yielded 4.098 articles but only 15 were relevant: 1.217
      patients underwent surgery. The interval time between fistula's diagnosis and
      operative repair was between 3 months and 1 year. A bowel resection with primary
      anastomosis was performed in 1.048 patients, 192 (18.3%) underwent a covering
      stoma: 856 patients (81.7%) had a fistula takedown in one procedure. RESULTS: The
      patients had 14.3% recurrence and 13.1% mortality rate. In our experience 75%
      were surgically treated after a period equal or above one year from fistula
      occurrence: surgery was very demolitive (in 40% remnant small bowel was less than
      100 cm). We performed a bowel resection with a hand-sewn anastomosis (95%)
      without temporary stoma. In-hospital mortality was 0% and at discharge all were
      back to oral intake with 0% early re-fistulisation. CONCLUSIONS: Literature
      supports our experience: ECF takedown could be safely performed after an adequate
      period of recovery from 3 months to one year from fistula occurrence. In our
      series primary repair (bowel resection plus reconnection surgery without
      temporary stoma) avoided an early recurrence without mortality.

PMID- 29182903
TI  - Total laparoscopic splenectomy for giant epidermoid cyst: a case report.
AB  - INTRODUCTION: Splenic cysts are benign tumors, accidentally detected using US or
      CT scan. They are classified into true cyst (primary, 25%) and pseudocyst
      (secondary, 75%). Conventional treatment of splenic cyst, especially giant,
      symptomatic and complicated has been open or laparoscopic total splenectomy.
      Recently, partial splenectomy is recommended as well to preserve its
      hematopoietic function and homeostasis of blood, but it is not considered safe
      for complications as intra and post operative bleeding. CASE REPORT: A 46 years
      old man, martial arts practitioner, underwent US abdomen scan because of left
      upper quadrant pain, with evidence of a splenic mass. He underwent also CT and
      MRI, which revealed "oval giant splenic mass of 12 cm diameter located in
      superior splenic pole that can be firstly referred to cyst". Considered patient's
      frequency to thoraco-abdominal traumas, we decided to perform a total
      laparoscopic splenectomy. Surgical treatment was performed with a three trocar
      technique and lasted 150 minutes. Post-operative follow-up was regular and
      abdominal drain was removed in 4th POD (Post Operative Day). Patient was
      discharged in 5th POD. Pathological examination revealed epidermoid cyst.
      CONCLUSIONS: Total splenectomy needs to be performed in cases of giant cyst and
      in our limited experience it is a safe approach.

PMID- 29182904
TI  - Spontaneous splenic artery aneurysm rupture in a 38-year old female: a case
      report.
AB  - Splenic artery aneurysm (SAA) is a rare and extremely difficult diagnosis. A rare
      case of a ruptured SAA in a 38-year old female, firstly treated with endovascular
      embolization and then with splenectomy, is presented. A 38-year old female
      presented to the emergency department with epigastric pain and fainting episodes.
      Direct catheter angiography revealed a ruptured SAA and distal, as well as
      proximal coil embolization was performed. Due to abdominal compartment syndrome
      the patient underwent open surgery with splenic artery ligation and splenectomy.
      Postoperative she showed signs of sepsis and was treated with i.v. fluids,
      steroids, packed red blood cells, platelets, fresh frozen plasma and
      antimicrobial treatment. Additionally, a multidrug resistant Acinetobacter
      baumanni was yielded from the urine culture. She had a satisfactory recovery. She
      is followed up a total of 5 years with no signs of overwhelming post-splenectomy
      infection syndrome. Direct catheter angiography is a very helpful option in
      diagnosis, as well as treatment, but a close monitoring after embolization is
      essential. Furthermore, post-splenectomy sepsis is a severe disease with high
      mortality rates that requires immediate appropriate treatment.

PMID- 29182905
TI  - Is There a Difference in Intra-Articular Injections of Corticosteroids,
      Hyaluronate, or Placebo for Temporomandibular Osteoarthritis?
AB  - PURPOSE: Corticosteroids are widely used for treatment of temporomandibular joint
      (TMJ) osteoarthritis (OA). This study investigated the effects of corticosteroids
      on TMJOA compared with placebo or hyaluronate. MATERIALS AND METHODS: The authors
      designed and implemented a systematic review and meta-analysis to compare the
      effects of intra-articular injection of corticosteroid, hyaluronate, or placebo
      for patients with TMJOA. The authors searched related randomized controlled
      studies electronically in multiple English- and Chinese-language electronic
      databases. The predictor variable was intra-articular injection with
      corticosteroid, hyaluronate, or placebo. Primary outcome variables were pain
      intensity and maximal mouth opening. Other variables included success rate and
      adverse events. Meta-analyses were performed with Rev Man 5.3. RESULTS: Eight
      studies met the inclusion criteria. Meta-analysis showed that corticosteroid
      injections after arthrocentesis were superior to placebo in relieving pain as
      assessed with the visual analog scale (mean difference [MD], -0.74; 95%
      confidence interval [CI], -1.34 to -0.13; P = .02; I2 = 0%) in the long-term, but
      was inferior in increasing maximal mouth opening (MD, -2.06; 95% CI, -2.76 to 
      1.36; P < .00001; I2 = 28%). Although corticosteroid and hyaluronate injections
      without arthrocentesis decreased pain and improved maximal mouth opening, the
      corticosteroid group had a significantly lower success rate (odds ratio = 0.41;
      95% CI, 0.17-1.00; P = .05; I2 = 0%) than the hyaluronate group in the short
      term. CONCLUSION: Corticosteroid injections after arthrocentesis are recommended
      for patients with TMJOA to relieve joint pain rather than increase maximal mouth
      opening. Corticosteroid and hyaluronate have marked effectiveness on TMJOA;
      however, hyaluronate might be the better alternative to some extent.

PMID- 29182906
TI  - Effect of polymyxin B-containing regimens on renal function for the treatment of
      carbapenem-resistant Enterobacteriacea mediastinitis.
AB  - A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides or
      polymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in
      26 (86.6%) patients. The median time to acute kidney injury was 6.0 (95% CI 3-14)
      days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95%
      CI 6-42) days in the polymyxin with other antimicrobial combinations group
      (p=0.03). Polymyxin B with aminoglycosides group progressed faster to any degree
      of renal dysfunction.

PMID- 29182907
TI  - Evaluation of the suitability of a plant virus, pepper mild mottle virus, as a
      surrogate of human enteric viruses for assessment of the efficacy of coagulation
      rapid sand filtration to remove those viruses.
AB  - Here, we evaluated the removal of three representative human enteric viruses -
      adenovirus (AdV) type 40, coxsackievirus (CV) B5, and hepatitis A virus (HAV) IB 
      and one surrogate of human caliciviruses - murine norovirus (MNV) type 1 - by
      coagulation-rapid sand filtration, using water samples from eight water sources
      for drinking water treatment plants in Japan. The removal ratios of a plant virus
      (pepper mild mottle virus; PMMoV) and two bacteriophages (MS2 and phiX174) were
      compared with the removal ratios of human enteric viruses to assess the
      suitability of PMMoV, MS2, and phiX174 as surrogates for human enteric viruses.
      The removal ratios of AdV, CV, HAV, and MNV, evaluated via the real-time
      polymerase chain reaction (PCR) method, were 0.8-2.5-log10 when commercially
      available polyaluminum chloride (PACl, basicity 1.5) and virgin silica sand were
      used as the coagulant and filter medium, respectively. The type of coagulant
      affected the virus removal efficiency, but the age of silica sand used in the
      rapid sand filtration did not. Coagulation-rapid sand filtration with non
      sulfated, high-basicity PACls (basicity 2.1 or 2.5) removed viruses more
      efficiently than the other aluminum-based coagulants. The removal ratios of MS2
      were sometimes higher than those of the three human enteric viruses and MNV,
      whereas the removal ratios of phiX174 tended to be smaller than those of the
      three human enteric viruses and MNV. In contrast, the removal ratios of PMMoV
      were similar to and strongly correlated with those of the three human enteric
      viruses and MNV. Thus, PMMoV appears to be a suitable surrogate for human enteric
      viruses for the assessment of the efficacy of coagulation-rapid sand filtration
      to remove viruses.

PMID- 29182908
TI  - Outdoor and indoor air quality and cognitive ability in young children.
AB  - BACKGROUND: This study examined outdoor and indoor air quality at ages 9 months
      and 3 years and their association with cognitive ability at age 3 in England and
      Wales. METHOD: Data from 8198 Millennium Cohort Study children were analysed
      using multilevel regression. Outdoor air quality was assessed with mean annual
      estimates of nitrogen dioxide (NO2) levels within a standard small area (ward).
      Indoor air quality was measured with parent-reports of damp or condensation in
      the home and exposure to secondhand smoke in the home. Cognitive ability was
      assessed with the British Ability Scales Naming Vocabulary subscale and the
      Bracken School Readiness Assessment. RESULTS: In adjusted models, consistent
      exposure to high levels of NO2 at age 9 months and age 3 years was associated
      with lower verbal ability at age 3 years. Damp/condensation and secondhand smoke
      in the home at either age or at both ages were correlated with lower school
      readiness at age 3 years. Exposures to damp/condensation at age 3 years or at
      both ages and secondhand smoke at either age or at both ages were associated with
      lower verbal ability at age 3 years. CONCLUSION: Young children's exposures to
      indoor damp or condensation and secondhand smoke are likely to be detrimental for
      their cognitive outcomes. However, there do not appear to be any short-term
      effects of NO2.

PMID- 29182909
TI  - Association between media coverage and prevalence of idiopathic environmental
      intolerance attributed to electromagnetic field in Taiwan.
AB  - Idiopathic environmental intolerance attributed to electromagnetic fields (IEI
      EMF) describes symptoms sufferers attribute to exposure to electromagnetic fields
      (EMF). In Taiwan, the prevalence rate of IEI-EMF was 13.3% in 2007, but a survey
      using the same method found the rate declined to 4.6% in 2012. Because media
      reports may encourage readers to attribute their symptoms to EMF, the change
      might be related to media coverage. We searched articles indexed in the largest
      newspaper database in Taiwan to evaluate the association between media coverage
      and the prevalence of IEI-EMF. We also assessed the effects of other potential
      affecting factors. The number of newspaper articles related to EMF and IEI-EMF
      increased from 2005 to 2007 and then has been decreasing until 2012, which is
      compatible with the change in the prevalence of IEI-EMF. However, from 2007 to
      2012, the other potential affecting factors such as density of mobile phone base
      stations, number of mobile phone users, total mobile phone calling time, and
      number of text messages sent through mobile phones all increased in Taiwan. This
      finding indicated a positive association between media coverage and the
      prevalence of IEI-EMF in Taiwan, which might also be true in other countries.

PMID- 29182910
TI  - Peptide-based biosensors: From self-assembled interfaces to molecular probes in
      electrochemical assays.
AB  - Redox-tagged peptides have emerged as functional materials with multiple
      applications in the area of sensing and biosensing applications due to their high
      stability, excellent redox properties and versatility of biomolecular
      interactions. They allow direct observation of molecular interactions in a wide
      range of affinity and enzymatic assays and act as electron mediators. Short
      helical peptides possess the ability to self-assemble in specific configurations
      with the possibility to develop in highly-ordered, stable 1D, 2D and 3D
      architectures in a hierarchical controlled manner. We provide here a brief
      overview of the electrochemical techniques available to study the electron
      transfer in peptide films with particular interest in developing biosensors with
      immobilized peptide motifs, for biological and clinical applications.

PMID- 29182911
TI  - Electrode-based AC electrokinetics of proteins: A mini-review.
AB  - Employing electric phenomena for the spatial manipulation of bioparticles from
      whole cells down to dissolved molecules has become a useful tool in biotechnology
      and analytics. AC electrokinetic effects like dielectrophoresis and AC
      electroosmosis are increasingly used to concentrate, separate and immobilize DNA
      and proteins. With the advance of photolithographical micro- and nanofabrication
      methods, novel or improved bioanalytical applications benefit from concentrating
      analytes, signal enhancement and locally controlled immobilization by AC
      electrokinetic effects. In this review of AC electrokinetics of proteins, the
      respective studies are classified according to their different electrode
      geometries: individual electrode pairs, interdigitated electrodes, quadrupole
      electrodes, and 3D configurations of electrode arrays. Known advantages and
      disadvantages of each layout are discussed.

PMID- 29182912
TI  - SMC complexes sweeping through the chromosome: going with the flow and against
      the tide.
AB  - Bacteria transcribe, duplicate and segregate their genomes all at once. Conflicts
      between DNA replication and active transcription are a major source of DNA damage
      and jeopardize genome integrity and cell survival. Co-orientation of replication
      forks and transcription units is thought to reduce the impact of such conflicts.
      Like transcription and replication, chromosome segregation relies on the
      translocation of multi-subunit protein complexes along DNA. Here, I highlight
      recent advances in our understanding of two major classes of structural
      maintenance of chromosomes (SMC) complexes in bacteria: Smc-ScpAB, whose DNA
      translocation is co-oriented with DNA replication by specific start sites, and
      MukBEF, which apparently lacks such co-ordination. Potential advantages of
      centralized and decentralized approaches to chromosome organization are
      discussed.

PMID- 29182913
TI  - A Student Selected Component (or Special Study Module) in Forensic and Legal
      Medicine: Design, delivery, assessment and evaluation of an optional module as an
      addition to the medical undergraduate core curriculum.
AB  - The General Medical Council (United Kingdom) advocates development of non-core
      curriculum Student Selected Components and their inclusion in all undergraduate
      medical school curricula. This article describes a rationale for the design,
      delivery, assessment and evaluation of Student Selected Components in Forensic
      and Legal Medicine. Reference is made to the available evidence based literature
      pertinent to the delivery of undergraduate medical education in the subject area.
      A Student Selected Component represents an opportunity to highlight the
      importance of the legal aspects of medical practice, to raise the profile of the
      discipline of Forensic and Legal Medicine amongst undergraduate medical students
      and to introduce students to the possibility of a future career in the area. The
      authors refer to their experiences of design, delivery, assessment and evaluation
      of Student Selected Components in Forensic and Legal Medicine at their respective
      Universities in the Republic of Ireland (Galway) and in the United Kingdom
      (Oxford).

PMID- 29182914
TI  - Detection of proximal conduction blocks using a triple stimulation technique
      improves the early diagnosis of Guillain-Barre syndrome.
AB  - OBJECTIVE: Current diagnostic electrophysiological criteria can miss the early
      stages of Guillain-Barre syndrome (GBS). We evaluated the diagnostic efficiency
      of the triple stimulation technique (TST) in highlighting proximal conduction
      blocks (CBs) in patients who do not meet the electrophysiological criteria for
      GBS. METHODS: All patients with a diagnosis of clinical GBS referred to our
      center between September 2014 and January 2016 were included in the study. For
      patients who did not fulfill the electrophysiological criteria of GBS, we
      performed the TST examination. RESULTS: Among the 44 included patients, 86%
      fulfilled the electrophysiological criteria of GBS during the initial nerve
      conduction study (NCS). The six remaining patients had proximal CBs revealed by
      TST examination. Therefore, a combination of a conventional NCS and the TST
      allowed 100% of the patients to be electrophysiologically diagnosed. CONCLUSIONS:
      TST is useful for the diagnosis of GBS in association with NCS, particularly in
      the early stages of the disease. SIGNIFICANCE: TST is a useful tool for GBS
      diagnosis at the early stages of the disease.

PMID- 29182915
TI  - Event-related neuronal responses to acoustic novelty in single-sided deaf
      cochlear implant users: Initial findings.
AB  - OBJECTIVE: A cochlear implant (CI) is an auditory prosthesis restoring profound
      hearing loss. However, CI-transmitted sounds are degraded compared to normal
      acoustic hearing. We investigated cortical responses related to CI-degraded
      against acoustic listening. METHODS: Event-related potentials (ERPs) were
      recorded from eight single-sided deaf CI users who performed a three-stimulus
      oddball task, separately with their normal hearing ear and CI ear. The oddball
      tones were occasionally intermitted by novel sounds. ERP responses were compared
      between electric and acoustic listening for the auditory (N1) and auditory
      cognitive (Novelty P3, Target-P3) ERP components. RESULTS: CI-degraded listening
      was associated with attenuated sensory processing (N1) and with attenuated early
      cortical responses to acoustic novelty whereas the late cortical responses to
      acoustic novelty and the target-P3 did not differ between NH and CI ears.
      CONCLUSION: The present study replicates the CI-attenuation of Novelty-P3
      amplitudes in a within-subject comparison. Further, we show that the CI
      attenuation of Novelty-P3 amplitudes extends to early cortical responses to
      acoustic novelty, but not to late novelty responses. SIGNIFICANCE: The
      dissociation into CI-attenuated P3 early Novelty-P3 amplitudes and CI-unaffected
      late Novelty-P3 amplitudes represents a cortical fingerprint of CI-degraded
      listening. It further contributes to general claims of distinct auditory Novelty
      P3 sub-components.

PMID- 29182916
TI  - What is the optimal frequency range for quantifying slow EEG activity in
      neonates? Insights from power spectra.

PMID- 29182917
TI  - Natural radioactivity in soils of the state of Rio de Janeiro (Brazil):
      Radiological characterization and relationships to geological formation, soil
      types and soil properties.
AB  - Located in the south-western part of Brazil, the state of Rio de Janeiro is
      geotectonically contained within a complex structural province that resulted in
      the amalgamation of the Western Gondwana Paleocontinent. To undertake an
      extensive radiological characterization of this complex geological province and
      investigate the influence of bedrock, soil type and soil chemical-physical
      characteristics on natural radionuclide levels in soils, 259 surface soil samples
      were collected that encompassed the main soil types and geological formations
      throughout the state. Gamma spectrometry analysis of the samples resulted in
      median values of 114 Bq.kg-1for 40K, 32 Bq.kg-1 for 226Ra and 74 Bq.kg-1 for
      228Ra. The median value for 226Ra was similar to the world median value for
      soils, the 40K value was well below the worldwide value, and that for 228Ra
      exceeded the world median value. The intense weathering caused by the high
      rainfall rates and high temperatures may be responsible for the low levels of 40K
      in the soils, of which the strongly acidic and clayey soils are markedly K
      depleted. A soil from a high-grade metamorphic rock (granulite) presented the
      lowest 226Ra (18 Bq.kg-1) content, whereas the highest levels for 226Ra (92 Bq.kg
      1) and 228Ra (139 Bq.kg-1) were observed in a young soil enriched in primary
      minerals (Leptsol). A lowland soil (Gleysol) showed the highest median of 40K
      (301 Bq.kg-1). Strongly acidic soils tended to present high amounts of 226Ra, and
      sandy soils tended to contain low levels of 228Ra. The external radiation dose
      indicates that the state has a background radiation level within the natural
      range.

PMID- 29182918
TI  - Clustering analysis strategies for electron energy loss spectroscopy (EELS).
AB  - In this work, the use of cluster analysis algorithms, widely applied in the field
      of big data, is proposed to explore and analyze electron energy loss spectroscopy
      (EELS) data sets. Three different data clustering approaches have been tested
      both with simulated and experimental data from Fe3O4/Mn3O4 core/shell
      nanoparticles. The first method consists on applying data clustering directly to
      the acquired spectra. A second approach is to analyze spectral variance with
      principal component analysis (PCA) within a given data cluster. Lastly, data
      clustering on PCA score maps is discussed. The advantages and requirements of
      each approach are studied. Results demonstrate how clustering is able to recover
      compositional and oxidation state information from EELS data with minimal user
      input, giving great prospects for its usage in EEL spectroscopy.

PMID- 29182919
TI  - An atomic force microscopy mode for nondestructive electromechanical studies and
      its application to diphenylalanine peptide nanotubes.
AB  - Nondestructive scanning probe microscopy of fragile nanoscale objects is
      currently in increasing need. In this paper, we report a novel atomic force
      microscopy mode, HybriD Piezoresponse Force Microscopy (HD-PFM), for simultaneous
      nondestructive analysis of piezoresponse as well as of mechanical and dielectric
      properties of nanoscale objects. We demonstrate this mode in application to self
      assembled diphenylalanine peptide micro- and nanotubes formed on a gold-covered
      substrate. Nondestructive in- and out-of-plane piezoresponse measurements of
      tubes of less than 100 nm in diameter are demonstrated for the first time. High
      resolution maps of tube elastic properties were obtained simultaneously with HD
      PFM. Analysis of the measurement data combined with the finite-elements
      simulations allowed quantification of tube Young's modulus. The obtained value of
      29 +/- 1 GPa agrees well with the data obtained with other methods and reported
      in the literature.

PMID- 29182920
TI  - Effect of asymmetric morphology on coupling surface plasmon modes and generalized
      plasmon ruler.
AB  - Plasmon coupling in aggregated noble metal systems can provide a path to
      manipulate the optical response purposefully and possesses a wide range of
      application. Previously, most studies focused on the coupling behavior of Ag-Ag
      dimers with the same shape. However, plasmon coupling between nanoparticles at
      different morphologies can provide a new way to modulate optical properties due
      to broken of symmetry. In this work, we investigate systematically the coupling
      modes of asymmetric Ag-Ag heterodimers consisting of different morphologies by
      the boundary element method (BEM). Herein nanoparticles with different surface
      curvatures (modified by rounding parameter e) are constructed and combined as
      asymmetric Ag-Ag heterodimers. Simulated electron energy loss spectroscopy (EELS)
      spectra and eigenmodes are combined to analyze the evolution of coupling modes.
      The mode energy degeneracy and degeneracy breaking phenomena are found, while the
      charge states are always not degenerate, for the first time by modulating
      symmetry of the morphology. It is also found that coupling gap mode G2 can only
      be excited for Ag-Ag heterodimers with quite small separation distance, and will
      be greatly influenced by nanogap morphology. The rounded effect can also cause
      distinct blue shift of bounding dipolar modes. These results provide the
      possibility to modulate optical response by using different asymmetric dimers
      effectively. In contrast, optical response of high-order coupling modes is less
      sensitive to topographic effect than that of low-order coupling modes. Moreover,
      plasmon ruler for asymmetric Ag-Ag heterodimers is investigated and we
      demonstrate that a generalized plasmon ruler is applicable to predict the
      relative shift of coupling dipolar due to change of separation distance.

PMID- 29182921
TI  - Hydroxypyridinone-benzofuran hybrids with potential protective roles for
      Alzheimer's disease therapy.
AB  - A series of (3-hydroxy-4-pyridinone)-benzofuran hybrids have been developed and
      studied as potential multitargeting drugs for Alzheimer's disease (AD). Their
      design envisaged mainly to mimic the donepezil drug, a marketed inhibitor of
      acetylcholinesterase (AChE), and to endow the conjugate molecules with extra
      properties such as metal chelation, radical scavenging and inhibition of amyloid
      peptide (Abeta) aggregation. Thus, a set of eleven new hybrid compounds was
      developed and evaluated for chemical and biological properties, in solution and
      in neuronal cell environment. The results are discussed in terms of the type of
      substituents on both main moieties and the linker size. The closest similarity
      with donepezil, in terms of AChE inhibitory activity, was obtained for the O
      benzyl-hydroxypyridinone hybrids containing a 2-methylene linker, although still
      less active than the drug. However, the free-hydroxypyridinone hybrids present
      higher activity for the Abeta aggregation inhibition, metal chelating capacity
      and radical scavenging activity. Overall, some compounds demonstrated capacity to
      exert a multiple action by hitting three- (7d) or four- (8d, 8f)
      pathophysiological targets of AD. Furthermore, the compounds showed
      neuroprotective effects in neuronal cells subjected to model stressors of AD, but
      not significant dependence on the substituent groups. Importantly, the compounds
      evidenced drug-likeness properties, including good membrane permeability.

PMID- 29182923
TI  - Association between dietary patterns and depressive symptoms among middle-aged
      adults in China in 2016-2017.
AB  - The purpose of this study was to explore the associations of dietary patterns
      with depressive symptoms in middle-aged Chinese adults. The cross-sectional study
      participants were 1360 Chinese adults (45-59 years, 659 males and 701 females)
      who participated in a Health Survey at the time of periodic checkup. Dietary
      intakes were assessed via a semi-quantitative food frequency questionnaire (FFQ).
      Binary logistic regression analysis was used to estimate odds ratio(OR) and 95%
      confidence interval(CI) for depressive symptoms according to quartiles of each
      dietary pattern score. Four major dietary patterns were identified by factor
      analysis: traditional Chinese, Western, grains-vegetables and high-salt patterns.
      After controlling for potential confounders, participants in the highest quartile
      of the Western pattern scores had greater odds of depressive symptoms than those
      in the lowest quartile. In contrast, participants in the highest quartile of the
      grains-vegetables pattern had lower odds of depressive symptoms than those in the
      lowest quartile. Nevertheless, no significant associations were observed between
      the traditional Chinese and high-salt patterns and the risk of depressive
      symptoms, even after adjusting for potential confounders. The findings indicate
      that the Western pattern is associated with an increased risk, and the grains
      vegetables pattern is associated with a reduced risk of depressive symptoms.

PMID- 29182922
TI  - Quantitative trait loci for sensitivity to acute ethanol and ethanol consummatory
      behaviors in rats.
AB  - Individuals with a low initial response to alcohol (i.e., ethanol) are at greater
      risk of developing alcohol abuse or dependence later in life. Similar to humans,
      individual differences in ethanol sensitivity also can be seen in rats, and
      several laboratories have used these individual differences to generate
      selectively bred rats that differ in acute ethanol sensitivity. We have worked
      with two sets of such rats (Inbred High or Low Alcohol Sensitivity strains, IHAS
      or ILAS, respectively; Inbred Alcohol Tolerant or Non-Tolerant strains, IAT and
      IANT, respectively) and have confirmed previously mapped quantitative trait loci
      (QTL) for these acute differences with the use of recombinant congenic lines;
      however, the relationship between acute sensitivity and ethanol drinking in these
      rats has yet to be determined. Thus, here we tested the hypothesis that QTLs
      underlying variation in initial low sensitivity to ethanol also will modulate
      variation in ethanol drinking behaviors. Separate groups of selectively inbred
      parent and congenic rats were tested for the loss of righting response (LORR) and
      also assessed for ethanol consummatory behavior using either operant self
      administration or an intermittent-access two-bottle choice procedure. LORR
      testing confirmed the presence of a LORR duration QTL in all of the congenics;
      however, the lack of a corresponding difference in blood ethanol concentration at
      the regaining of the righting response suggests that these QTLs may be mediating
      a difference in ethanol metabolism rather than in neuronal sensitivity. IHAS/ILAS
      derived congenic rats did not differ from parent rats at any point during operant
      self-administration. IAT/IANT-derived congenic rats showed small, but
      significant, increases in ethanol consumption relative to the parent strains only
      during the initial stages of operant self-administration. In contrast to operant
      testing, IHAS/ILAS-derived congenic rats showed significantly greater ethanol
      consumption and preference than parent rats during intermittent-access testing.
      There were not differences, however, between IAT/IANT congenic and parent rats
      during intermittent access. These data support the hypothesis that there is a
      genetic relationship between initial ethanol sensitivity and ethanol consumption,
      at least for the IHAS/ILAS-derived congenic rats. Our current studies, however,
      cannot eliminate pharmacokinetic or taste preference factors as contributing to
      the rats' responses, nor can we eliminate the possibility of a linkage effect
      because of the fairly large size of the QTL intervals; i.e., distinct genes may
      be mediating the acute sensitivity and drinking responses.

PMID- 29182924
TI  - Control of anthracnose caused by Colletotrichum species in guava, mango and
      papaya using synergistic combinations of chitosan and Cymbopogon citratus (D.C.
      ex Nees) Stapf. essential oil.
AB  - This study assessed the efficacy of chitosan (Chi) and Cymbopogon citratus (D.C.
      ex Nees) Stapf. essential oil (CCEO) combinations to control the mycelial growth
      of five pathogenic Colletotrichum species (C. asianum, C. siamense, C.
      fructicola, C. tropicale and C. karstii) in vitro, as well as the anthracnose
      development in guava (Psidium guajava L.) cv. Paluma, mango (Mangifera indica L.)
      cv. Tommy Atkins and papaya (Carica papaya L.) cv. Papaya artificially inoculated
      with these species. Combinations of Chi (2.5, 5 or 7.5mg/mL) and CCEO (0.15, 0.3,
      0.6 or 1.25MUL/mL) inhibited the mycelial growth of all tested fungal species in
      vitro. Examined Chi-CCEO combinations showed additive or synergistic interactions
      to inhibit the target Colletotrichum species based on the Abbott index. Coatings
      formed by synergistic Chi (5mg/mL) and CCEO (0.15, 0.3 or 0.6MUL/mL) combinations
      decreased anthracnose lesion development in guava, mango and papaya inoculated
      with any of the tested Colleotrichum species during storage. Overall, anthracnose
      lesion development inhibition in fruit coated with synergistic Chi-CCEO
      combinations was higher than that observed in fruit treated with synthetic
      fungicides. These results show that the application of coatings formed by Chi
      CCEO synergistic combinations could be effective to control postharvest
      anthracnose development in fruit.

PMID- 29182925
TI  - To reveal the nature of interactions of human hemoglobin with gold nanoparticles
      having two different morphologies (sphere and star-shaped) by using various
      spectroscopic techniques.
AB  - The nature of interactions between heme protein human hemoglobin (HHb) and gold
      nanoparticles of two different morphologies that is GNP (spherical) and GNS (star
      shaped) have been investigated by using UV-vis absorption, steady state
      fluorescence, synchronous fluorescence, resonance light scattering (RLS), time
      resolved fluorescence, FT-IR, and circular dichroism (CD) techniques under
      physiological condition of pH ~7 at ambient and different temperatures. Analysis
      of the steady state fluorescence quenching of HHb in aqueous solution in the
      presence of GNP and GNS suggests that the nature of the quenching is of static
      type. The static nature of the quenching is also confirmed from time resolved
      data. The static type of quenching also indicates the possibility of formation of
      ground state complex for both HHb-GNP and HHb-GNS systems. From the measurements
      of Stern-Volmer (SV) constants KSV and binding constants, KA and number of
      binding sites it appears that HHb forms stronger binding with GNP relative to
      GNS. Analysis of the thermodynamic parameters indicates that the formation of HHb
      GNP and HHb-GNS complexes are spontaneous molecular interaction processes (?G<0).
      In both cases hydrogen bonding and van der Waals interactions play a dominant
      role (?H<0, ?S<0). Synchronous fluorescence spectroscopy further reveals that the
      ground state complex formations of HHb-GNP and HHb-GNS preferably occur by
      binding with the amino acid tyrosine through hydrogen bonding interactions.
      Moreover the alpha-helicity contents of the proteins as obtained from the
      circular dichroism (CD) spectra appears to be marginally reduced by increasing
      concentrations of GNP and GNS and the alpha-helical structures of HHb retain its
      identity as native secondary structure in spite of complex formations with GNP or
      GNS. These findings demonstrate the efficiency of biomedical applications of GNP
      and GNS nanoparticles as well as in elucidating their mechanisms of action as
      drugs or drug delivery systems in human.

PMID- 29182926
TI  - Poly (dopamine quinone-chromium (III) complex) microspheres as new modifier for
      simultaneous determination of phenolic compounds.
AB  - In this study, poly(dopamine-quinone chromium (III))-microspheres (PDQCM) were
      used for the modification of graphite paste electrode (GPE) for simultaneous
      voltammetric determination of 4-Amino Phenol (AP), Phenol (Ph) and 4-Nitro Phenol
      (NP). The PDQCM and the GPE modified with PDQCM were characterized by field
      emission scanning electron microscopy, Energy-dispersive X-ray spectroscopy,
      Fourier transform infrared spectroscopy, electrochemical impedance spectroscopy
      and electrochemistry methods such as cyclic voltammetry (CV) and differential
      pulse voltammetry (DPV). The proposed modified electrode exhibits high
      electrocatalytic activity toward electrooxidation of AP, Ph, and NP to three well
      separated peaks in the potential range from 0.2 to 1.3V using CV and DPV methods
      in phosphate buffer solution with pH 2.0. Under the optimum conditions, detection
      limits of 0.5, 0.6 and 0.8uM were obtained for AP, Ph, and NP, respectively.
      Moreover, GPE/PDQCM was successfully used for simultaneous determination of AP,
      Ph, and NP in tap and river waters.

PMID- 29182927
TI  - Insights into a hole transfer mechanism between glucose oxidase and a p-type
      organic semiconductor.
AB  - This manuscript describes a bioelectrochemical application of a new class of
      electrochemically generated hole-transporting (p-type) polymeric semiconductors
      (HTPS), which are based on a carbazole core and the oxiran and thiiran reactive
      groups. Electrode based on transparent layer of indium tin oxide was
      electrochemically modified with a layer of HTPS and a monolayer of covalently
      immobilized glucose oxidase (GOx). The HTPS/GOx-based electrode was investigated
      for an evaluation of direct hole-transfer between the enzyme and electrode at a
      bio-electrochemically relevant potential via HTPS layer. The broad linear
      relationship between the peak-current density and glucose concentration from 2 to
      15mM and high stability of ITO/poly-CzS/GOx-electrode was observed. Moreover, it
      was determined that charge transfer rate constants are reliable for the
      establishment of advanced electron transfer between enzyme and electrode for the
      application of this HTPS/GOx-based electrode in long-lived biofuel cells and
      amperometric biosensors.

PMID- 29182928
TI  - Paper-based diagnostics in the antigen-depletion regime: High-density
      immobilization of rcSso7d-cellulose-binding domain fusion proteins for efficient
      target capture.
AB  - In this work, we report the development of a general strategy for enhancing the
      efficiency of target capture in immunoassays, using a bifunctional fusion protein
      construct which incorporates a substrate-anchoring moiety for the high-abundance
      immobilization of an antigen-binding domain. This approach was informed by the
      development of a pseudo first-order rate constant model, and tested in a paper
      based assay format using a fusion construct consisting of an rcSso7d binding
      module and a cellulose-binding domain. These rcSso7d-CBD fusion proteins were
      solubly expressed and purified from bacteria in high molar yields, and enable
      oriented, high-density adsorption of the rcSso7d binding species to unmodified
      cellulose within a 30-second incubation period. These findings were validated
      using two distinct, antigen-specific rcSso7d variants, which were isolated from a
      yeast surface display library via flow cytometry. Up to 1.6 micromoles of rcSso7d
      CBD was found to adsorb per gram of cellulose, yielding a volume-averaged binder
      concentration of up to 760MUM within the resulting active material. At this molar
      abundance, the target antigen is captured from solution with nearly 100%
      efficiency, maximizing the attainable sensitivity for any given diagnostic
      system.

PMID- 29182929
TI  - Nitration of tyrosine and its effect on DNA hybridization.
AB  - One major marker of nitrosative stress is the formation of 3-Nitrotyrosine (3-NT)
      from Tyrosine (Tyr) by adding a nitro group (-NO2) with nitrating agents.
      Nitration of Tyr often causes loss of protein activity and is linked with many
      diseases. In this article, we detect 3-NT and discriminate it from Tyr with
      Differential Pulse Voltammetry (DPV) as it is a very important biomarker. We
      first examined redox (oxidation/reduction) properties and stability of 3-NT in
      detail. Second, we provided the Tyr and 3-NT discrimination with DPV and compared
      with the chromatography. We then explored the interaction of 3-NT and DNA
      oligonucleotides. Our findings demonstrate that 3-NT can be used as a new
      electrochemical indicator, which is able to detect hybridization of probe (single
      stranded DNA-ssDNA) and hybrid (double stranded DNA-dsDNA) both via 3-NT
      reduction and guanine oxidation signal changes at the same time. The signal
      differences enabled us to distinguish ssDNA and dsDNA without using a label or a
      tag. Moreover, we achieved to detect hybridization of DNA by using the reduction
      signal of 3-NT obtained at -0.4V vs. Ag/AgCl. More importantly, we observed the
      changes of the reduction signals of 3-NT after the interaction of probe and
      hybrid sequences. We showed that 3-NT signal decreases more with hybrid than the
      probe. Our platform, for the first time, demonstrates the detection of
      hybridization both guanine oxidation and indicator reduction signal changes at
      the same time. Moreover, we, for the first time, demonstrated the interaction
      between 3-NT and DNA.

PMID- 29182930
TI  - Electrochemical immunosensors - A powerful tool for analytical applications.
AB  - Immunosensors are biosensors based on interactions between an antibody and
      antigen on a transducer surface. Either antibody or antigen can be the species
      immobilized on the transducer to detect antigen or antibody, respectively.
      Because of the strong binding forces between these biomolecules, immunosensors
      present high selectivity and very high sensitivity, making them very attractive
      for many applications in different science fields. Electrochemical immunosensors
      explore measurements of an electrical signal produced on an electrochemical
      transductor. This signal can be voltammetric, potentiometric, conductometric or
      impedimetric. Immunosensors utilizing electrochemical detection have been
      explored in several analyses since they are specific, simple, portable, and
      generally disposable and can carry out in situ or automated detection. This
      review addresses the potential of immunosensors destined for application in food
      and environmental analysis, and cancer biomarker diagnosis. Emphasis is given to
      the approaches that have been used for construction of electrochemical
      immunosensors. Additionally, the fundamentals of immunosensors, technology of
      transducers and nanomaterials and a general overview of the possible applications
      of electrochemical immunosensors to the food, environmental and diseases analysis
      fields are described.

PMID- 29182931
TI  - Surveying managers to inform a regionally relevant invasive Phragmites australis
      control research program.
AB  - Managers of invasive species consider the peer-reviewed literature only
      moderately helpful for guiding their management programs. Though this "knowing
      doing gap" has been well-described, there have been few efforts to guide
      scientists in how to develop useful and usable science. Here we demonstrate how a
      comprehensive survey of managers (representing 42 wetland management units across
      the Great Salt Lake watershed) can highlight management practices and challenges
      (here for the widespread invasive plant, Phragmites australis, a recent and
      aggressive invader in this region) to ultimately inform a research program. The
      diversity of surveyed organizations had wide-ranging amounts of Phragmites which
      led to different goals and approaches including more aggressive control targets
      and a wider array of control tools for smaller, private organizations compared to
      larger government-run properties. We found that nearly all managers (97%) used
      herbicide as their primary Phragmites control tool, while burning (65%),
      livestock grazing (49%), and mowing (43%) were also frequently used. Managers
      expressed uncertainties regarding the timing of herbicide application and type of
      herbicide for effective control. Trade-offs between different Phragmites
      treatments were driven by budgetary concerns, as well as environmental conditions
      like water levels and social constraints like permitting issues. Managers had
      specific ideas about the plant communities they desired following Phragmites
      control, yet revegetation of native species was rarely attempted. The results of
      this survey informed the development of large-scale, multi-year Phragmites
      control and native plant revegetation experiments to address management
      uncertainties regarding herbicide type and timing. The survey also facilitated
      initial scientist-manager communication, which led to collaborations and
      knowledge co-production between managers and researchers. An important outcome of
      the survey was that experimental results were more pertinent to manager needs and
      trusted by managers. Such an approach that integrates manager surveys to inform
      management experiments could be adapted to any developing research program
      seeking to be relevant to management audiences.

PMID- 29182932
TI  - Structure-based design for binding peptides in anti-cancer therapy.
AB  - The conventional anticancer therapeutics usually lack cancer specificity, leading
      to damage of normal tissues that patients find hard to tolerate. Ideally,
      anticancer therapeutics carrying payloads of drugs equipped with cancer targeting
      peptides can act like "guided missiles" with the capacity of targeted delivery
      toward many types of cancers. Peptides are amenable for conjugation to nano drugs
      for functionalization, thereby improving drug delivery and cellular uptake in
      cancer-targeting therapies. Peptide drugs are often more difficult to design
      through molecular docking and in silico analysis than small molecules, because
      peptide structures are more flexible, possess intricate molecular conformations,
      and undergo complex interactions. In this review, the development and application
      of strategies for structure-based design of cancer-targeting peptides against
      GRP78 are discussed. This Review also covers topics related to peptide
      pharmacokinetics and targeting delivery, including molecular docking studies,
      features that provide advantages for in vivo use, and properties that influence
      the cancer-targeting ability. Some advanced technologies and special peptides
      that can overcome the pharmacokinetic challenges have also been included.

PMID- 29182934
TI  - Your retirement and my health behavior: Evidence on retirement externalities from
      a fuzzy regression discontinuity design.
AB  - This paper presents evidence on intra-household retirement externalities by
      assessing the causal effect of spousal retirement on various health behaviors and
      health status across 19 European countries. We identify partner's and own
      retirement effects by applying a fuzzy regression discontinuity design using
      retirement eligibility as exogenous instruments for spousal and own retirement
      status. We find significant increases in the frequency and intensity of alcohol
      consumption combined with a significant decrease in moderate physical activities
      as a response to partner's retirement. In line with the existing literature, we
      find that own retirement has significant positive effects on engaging in moderate
      and vigorous physical activities but also leads to a significant increase in the
      frequency of alcohol intake. Overall, subjective health is negatively affected by
      spousal retirement and positively by own retirement.

PMID- 29182933
TI  - MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating
      apoptosis and modulating immune reactivity.
AB  - Mesenchymal stem cell (MSC) exosome was previously shown to be effective in
      repairing critical size osteochondral defects in an immunocompetent rat model.
      Here we investigate the cellular processes modulated by MSC exosomes and the
      mechanism of action underlying the exosome-mediated responses in cartilage
      repair. We observed that exosome-mediated repair of osteochondral defects was
      characterised by increased cellular proliferation and infiltration, enhanced
      matrix synthesis and a regenerative immune phenotype. Using chondrocyte cultures,
      we could attribute the rapid cellular proliferation and infiltration during
      exosome-mediated cartilage repair to exosomal CD73-mediated adenosine activation
      of AKT and ERK signalling. Inhibitors of AKT or ERK phosphorylation suppressed
      exosome-mediated increase in cell proliferation and migration but not matrix
      synthesis. The role of exosomal CD73 was confirmed by the attenuation of AKT and
      ERK signalling by AMPCP, a CD73 inhibitor and theophylline, an adenosine receptor
      antagonist. Exosome-treated defects also displayed a regenerative immune
      phenotype characterised by a higher infiltration of CD163+ regenerative M2
      macrophages over CD86+ M1 macrophages, with a concomitant reduction in pro
      inflammatory synovial cytokines IL-1beta and TNF-alpha. Together, these
      observations demonstrated that the efficient osteochondral regeneration by MSC
      exosomes was effected through a coordinated mobilisation of multiple cell types
      and activation of several cellular processes.

PMID- 29182935
TI  - Health care expenditures, age, proximity to death and morbidity: Implications for
      an ageing population.
AB  - This paper uses Hospital Episode Statistics, English administrative data, to
      investigate the growth in admitted patient health care expenditures and the
      implications of an ageing population. We use two samples of around 40,000
      individuals who (a) used inpatient health care in the financial year 2005/06 and
      died by the end of 2011/12 and (b) died in 2011/12 and had some hospital
      utilisation since 2005/06. We use a panel structure to follow individuals over
      seven years of this administrative data, containing estimates of inpatient health
      care expenditures (HCE), information regarding individuals' age, time-to-death
      (TTD), morbidities at the time of an admission, as well as the hospital provider,
      year and season of admission. We show that HCE is principally determined by
      proximity to death rather than age, and that proximity to death is itself a proxy
      for morbidity.

PMID- 29182936
TI  - Does health insurance coverage fall when nonprofit insurers become for-profits?
AB  - In exchange for tax exemptions, Blue Cross and Blue Shield (BCBS) health insurers
      were expected to provide health insurance to the "bad risks," those for whom
      coverage was unavailable from other insurers. I present evidence that five years
      after a BCBS plan converted to for-profit status, the probability of having
      insurance was 1.4 percentage points higher, a 9% reduction in the uninsured. The
      increase in coverage does not mask reductions among populations often targeted by
      public policies. However, there is evidence of increased risk selection which
      suggests that the bad risks might have been worse off after a conversion.

PMID- 29182937
TI  - Corrigendum to "Risk selection and heterogeneous preferences in health insurance
      markets with a public option" [J. Health Econ. 49 (2016) 153-168].

PMID- 29182938
TI  - Does disease cause vaccination? Disease outbreaks and vaccination response.
AB  - Parental fear of vaccines has limited vaccination rates in the United States. I
      test whether disease outbreaks increase vaccination using a new dataset of county
      level disease and vaccination data. I find that pertussis (whooping cough)
      outbreaks in a county decrease the share of unvaccinated children entering
      kindergarten. These responses do not reflect changes in the future disease risk.
      I argue that these facts are best fit by a model in which individuals are both
      myopic and irrational. This suggests that better promotion of information about
      outbreaks could enhance the response.

PMID- 29182939
TI  - The lyssavirus host-specificity conundrum-rabies virus-the exception not the
      rule.
AB  - Lyssaviruses are a diverse range of viruses which all cause the disease rabies.
      Of the 16 recognized species, only rabies viruses (RABV) have multiple host
      reservoirs. Although lyssaviruses are capable of infecting all mammals, onward
      transmission in a new host population requires adaptation of the virus, in a
      number of stages with both host and virus factors determining the outcome. Due to
      an absence of recorded non-RABV host shifts, RABV data is extrapolated to draw
      conclusions for all lyssaviruses. In this article, we have focused on evidence of
      host shifts in the same insectivorous bat reservoir species in North America
      (RABV) and Europe (EBLV-1, EBLV-2 and BBLV). How RABV has successfully crossed
      species barriers and established infectious cycles in new hosts to be the global
      multi-host pathogen it is today, whilst other lyssaviruses appear restricted in
      host species is explored in this review. It hypothesized that RABV is the
      exception, rather than the rule, in this fascinating genus of viruses.

PMID- 29182940
TI  - Clinical study of optical coherence tomography in the diagnosis of peripheral
      pulmonary artery thrombus.
AB  - BACKGROUND: Peripheral pulmonary artery thrombus (PPT) is common in the clinic.
      However, due to the lack of an ideal diagnostic tool, PPT cannot be quickly
      diagnosed and effectively treated at present. Optical coherence tomography (OCT)
      is a new intravascular imaging technique that is characterized by high image
      resolution. This technique is suitable for small vessel imaging and has the
      ability to distinguish red and white thrombi. OBJECTIVE: This study aimed to
      evaluate the value of OCT in the diagnosis of PPT and in identifying the nature
      of thrombi by comparing the difference in sensitivity between OCT and selective
      pulmonary angiography (SPA). METHODS: Highly suspected PPT patients were enrolled
      in this study. Pulmonary ventilation/perfusion (V/Q) mismatch pulmonary segments
      or peripheral pulmonary arteries were chosen. SPA was performed first, followed
      by OCT imaging. The diagnostic standard of thrombus with SPA was an intraluminal
      filling defect. The procedure and criteria for OCT diagnosis of thrombus were
      previously introduced in intracoronary OCT thrombus images. The diameter of the
      imaging vessels was measured, and they were grouped according to diameter. The
      diameter was <2mm in the distal segment group, 2-3mm in the middle segment group,
      and >3mm in the proximal segment group. The recognition abilities of
      intravascular thrombus with the different diameters of these two techniques were
      compared. Patients with obvious clinical symptoms and more red thromboses
      revealed by OCT were given standardized anticoagulant therapy for half a year.
      The clinical symptoms, 6-minute walking test and changes in the thrombus in the
      OCT images of these patients before and after treatment were observed. RESULTS: A
      total of 22 patients with highly suspected PPT were suggested to undergo V/Q
      inspection. Finally, 12 patients were eligible for the study. SPA and OCT were
      performed in 61 peripheral pulmonary arteries in all 12 patients. The ideal SPA
      and OCT images obtained from a total of 76 blood vessel segments were suitable
      for comparative analysis. A total of 62 thrombi were found by SPA. Among these,
      eight thrombi were in the distal segment, 29 thrombi were in the middle segment,
      and 25 thrombi were in the proximal segment. A total of 81 thrombi were found by
      OCT, among which 22 thrombi were in the distal segment, 31 were in the middle
      segment, and 28 were in the proximal segment. There was a significant difference
      between two groups in the distal segment group (P=0.013), while there was no
      significant difference between two groups in the middle segment group or the
      proximal segment group (P>0.05). In addition to all the thrombi found by SPA, OCT
      found other thrombi that were missed by SPA. According to previous OCT images for
      determining the nature of thrombi, OCT revealed 81 thrombi, of which 48 (59%)
      were red thrombi and 33 (41%) were white thrombi. Then, seven patients who had
      obvious clinical symptoms and more red thrombi in the peripheral pulmonary artery
      were given anticoagulant therapy for six months. After treatment, these symptoms
      were improved, oxygenation indexes increased, and the six-minute walking test was
      extended in all these patients. After anticoagulation therapy, five patients
      underwent OCT review. These OCT images were matched and compared before and after
      anticoagulation therapy. The results revealed that most of the thrombi had
      disappeared, and a small amount of red thrombi turned white as the volume
      reduced. The mean lumen area before and after treatment was 2.05+/-1.03mm2 and
      2.86+/-1.24mm2, respectively, and the difference was statistically significant
      (P=0.035). CONCLUSION: OCT can clearly show the structure of the lumen and the
      wall of the peripheral pulmonary artery tube. The sensitivity of the diagnosis of
      PPT with a diameter of <2mm was higher than that of SPA. Moreover, OCT has the
      ability to distinguish between red and white thrombi, which is of guiding
      significance in anticoagulant therapy.

PMID- 29182941
TI  - Magnetoencephalography reveals an increased non-target P3a, but not target P3b,
      that is associated with high non-clinical psychosocial deficits.
AB  - Auditory processing deficits are frequently identified in autism and
      schizophrenia, and the two disorders have been shown to share psychosocial
      difficulties. This study used magnetoencephalography to investigate auditory
      processing differences for those with a high degree of a non-clinical autistic
      and schizotypal trait phenotype, Social Disorganisation (SD). Participants were
      18 low (9 female) and 19 high (9 female) SD scorers (18-40 years) who completed a
      three-stimulus auditory oddball paradigm of speech sounds (standard: 100ms 'o',
      deviant: 150ms 'o', novel: 150ms 'e'). Spatio-temporal cluster analysis revealed
      increased amplitude for the high SD group in a left (p = 0.006) and a right (p =
      0.020) hemisphere cluster in response to the novel non-target. No cluster
      differences were found in response to the target deviant. These findings suggest
      that those with a high degree of the SD phenotype recruit more cortical resources
      when processing unattended, novel speech stimuli, which may lead to psychosocial
      deficits.

PMID- 29182942
TI  - Does MnTBAP ameliorate DNA fragmentation and in vivo fertility of frozen-thawed
      Arabian stallion sperm?
AB  - Overproduction of reactive oxygen species during sperm freeze-thawing process
      leads to membrane lipid peroxidation, DNA damage, motility loss, and subsequent
      death. This oxidative stress can be alleviated by the addition of some
      antioxidants to semen extenders prior to freezing. This study was performed to
      evaluate the in vitro effectiveness of MnTBAP (a cell permeable antioxidant) on
      stallion sperm freezability and in vivo fertility rate. Twenty-one ejaculates
      were, collected with missouri model artificial vagina (n = 3 stallions, seven
      ejaculate each), and diluted (1:2 v/v) with phosphocaseinate base INRA extender,
      containing 0 (control), 100, 200 and 300 MUM of MnTBAP and frozen using
      acontrolled-rate freezing system. The following parameters were determined: sperm
      motility, viability, membrane integrity, acrosome abnormalities, lipid
      peroxidation and DNA fragmentation. MnTBAP improved horse semen quality
      parameters in a dose-dependent manner. The100 MUM concentration of MnTBAP did not
      show a significant difference in semen parameters compare with control group (p >
      0.05). Accordingly, the extender supplemented with 200 MUM resulted in higher
      sperm total and progressive motility (55.3 +/- 4.28% and 33.2 +/- 2.90%),
      viability (43.9 +/- 2.14%), and membrane integrity (50.8 +/- 2.14%), provided a
      greater protective effect in the percentage of total abnormalities compare to
      other groups (p < 0.05), and showed lower sperm with damaged DNA with lower MDA
      levels (p < 0.001). Higher concentrations (300 MUM) not only did not improve the
      results but inversely affected sperm parameters. Twelve mares were used for
      fertility trial in the cross over study of 60 deep horn inseminations performed
      using control (9/30 pregnancy/mare) and 200 MUM - MnTBAP (14/30 pregnancy/mere)
      groups frozen semen. The Average pregnancy rates were not significantly different
      between control and treated group (30% and 46.66%respectively) (p > 0.05). Under
      the conditions of this study, 200 MUM - MnTBAP reduced the oxidative stress and
      protect the DNA fragmentation of Arabian stallion sperm during cryopreservation;
      but did not improved pregnancy rates.

PMID- 29182943
TI  - Effect of sorting boar spermatozoa by sex chromosomes on oviduct cell binding.
AB  - This study examined the hypothesis that flow sorting sperm by sex chromosomes
      affects oviduct cell binding which would influence formation of the sperm
      reservoir in the oviduct. The sperm-rich fraction from boars (n = 5) was
      collected, sperm were stained with Hoechst 33342 and sorted. Sperm were sorted
      based on the presence of either an X or Y chromosome and placed into the
      following treatments: 1) sperm selected for the Y chromosome, 2) selected for the
      X, 3) an equal mixture of sorted X and Y, and 4) a control of non-sorted sperm
      from the same collection. Samples were tested for oviduct cell binding within 12
      h of sorting. Additionally, sperm were analyzed for motility characteristics,
      acrosome status, and binding to the two oviduct glycan motifs that bind porcine
      sperm, biantennary 6-sialylated N-acetyllactosamine on a mannose core (bi-SiaLN)
      and sulfated LeX trisaccharide (suLeX). The disaccharide found within both glycan
      motifs, N-acetyllactosamine (LacNAc), was used as a control. Sperm binding to
      oviduct cells was reduced by more than half in the three sorted samples when
      compared to the control sperm that were not sorted. The percentage of sperm that
      were motile 24 h after sorting was also decreased significantly in each of the
      sorted sample groups when compared to the unsorted control. In contrast, sorting
      did not decrease the percentage of sperm that bound purified soluble glycans or
      the location on sperm to which they bound. There was also no difference in sperm
      acrosome status among the four groups. In summary, sorting reduced sperm binding
      to the complex matrix around oviductal cell aggregates but sperm binding to
      purified soluble oviduct glycans was not affected. The requirement for higher
      affinity and motility to bind glycans immobilized on oviduct cells may explain
      this difference. The reduction in sperm fertility observed following sex-sorting
      may be explained partially by a reduced or altered ability to bind to the oviduct
      epithelium.

PMID- 29182944
TI  - Learning to feel tired: A learning trajectory towards chronic fatigue.
AB  - Chronic fatigue complaints are frequently reported in the general population and
      fatigue ranks among the most commonly reported symptoms in chronic disease. In
      contrast to its high prevalence and impact on quality of life, relatively little
      is understood about the etiology of chronic fatigue. We present a cognitive
      behavioral framework, the 'ALT+F' model, that conceptualizes fatigue from an
      associative learning perspective, and we will evaluate the current evidence for
      this position. Central to this framework is the notion that interoceptive and
      exteroceptive stimuli can become associated with the fatigue experience.
      Consequently, these stimuli may acquire the capacity to elicit fatigue as well as
      anticipatory fear-related avoidance behavior. We will argue that associative
      learning processes may contribute to the development of chronic fatigue, fear of
      fatigue, avoidance of fatigue and activity, and eventually, functional
      disability. The extent to which associative learning processes give rise to
      chronic fatigue and fear-related avoidance behavior may depend on a number of
      risk factors, including perceptual-cognitive biases, sensitization, fatigue
      catastrophizing, and excessive generalization. The presented framework offers a
      new window on treatment and intervention options for chronic fatigue.

PMID- 29182946
TI  - Effect of pulse duration and pulse repetition frequency of cavitation histotripsy
      on erosion at the surface of soft material.
AB  - Cavitation histotripsy with the short pulse duration (PD) but high pulse
      repetition frequency (PRF) disintegrates the tissue at a fluid interface.
      However, longer PD and lower PRF are used in the other focused ultrasound
      applications, where the acoustic radiation force, streaming, and cavitation are
      different, and their effects on erosion are unknown. In this study, the erosion
      at the surface of phantom/ex vivo tissue and the characteristics of induced
      bubble cloud captured by high-speed photography, passive cavitation detection,
      and light transmission during histotripsy exposure at varied PDs and PRFs but the
      same duty cycle were compared. The peak negative pressure of 6.6 MPa at the PD of
      20 ms and PRF of 1 Hz began to erode the phantom, which becomes more significant
      with the increase of peak negative pressure, PD, and interval time between
      bursts. The increase of the PRF from 1 Hz to 1000 Hz, while the decrease of the
      PD from 20 ms to 20 MUs (duty cycle of 2%) at the same energy was delivered to
      the gel phantom immersed in the degassed water led to the decrease of erosion
      volume but a slight increase of the erosion area and smoother surface. Low PRF
      and long PD produce the significant tissue deformation, acoustic wave refocusing,
      confinement of bubbles in a conical region, and more bubble dissolution after the
      collapse for the high acoustic scattering and light transmission signals. In
      comparison, high PRF and low PD produce a wide distribution of bubbles with only
      little wave refocusing at the beginning of cavitation histotripsy and high
      inertial cavitation. Acoustic emission dose has a good correlation with the
      erosion volume. The erosion on the porcine kidney at the varied PRFs and PDs with
      the same energy output showed similar trends as those in the phantom but at a
      slow rate. In summary, the PRF and PD are important parameters for the cavitation
      histotripsy-induced erosion at the interface of fluid and soft material, and they
      should be optimized for the best outcome.

PMID- 29182945
TI  - Low-intensity pulsed ultrasound (LIPUS) stimulates mineralization of MC3T3-E1
      cells through calcium and phosphate uptake.
AB  - The present study aimed to evaluate the effect of low-intensity pulsed ultrasound
      (LIPUS) on pre-osteoblast mineralization using in vitro bioassays. Pre
      osteoblastic MC3T3-E1 cells were exposed to LIPUS at 1 MHz frequency, 0.2 W/cm2
      intensity and 20% duty cycle for 30 min. The analyses were carried out up to 336
      h (14 days) after exposure. The concentration of collagen, phosphate, alkaline
      phosphatase, calcium and transforming growth factor beta 1 (TGF-beta1) in cell
      supernatant and the presence of calcium deposits in the cells were analyzed. Our
      results showed that LIPUS promotes mineralized nodules formation. Collagen,
      phosphate, and calcium levels were decreased in cell supernatant at 192 h after
      LIPUS exposure. However, alkaline phosphatase and TGF-beta1 concentrations
      remained unchanged. Therapeutic pulsed ultrasound is capable of stimulating
      differentiation and mineralization of pre-osteoblastic MC3T3-E1 cells by calcium
      and phosphate uptake with consequent hydroxyapatite formation.

PMID- 29182947
TI  - Low-level neural auditory discrimination dysfunctions in specific language
      impairment-A review on mismatch negativity findings.
AB  - In specific language impairment (SLI), there is a delay in the child's oral
      language skills when compared with nonverbal cognitive abilities. The problems
      typically relate to phonological and morphological processing and word learning.
      This article reviews studies which have used mismatch negativity (MMN) in
      investigating low-level neural auditory dysfunctions in this disorder. With MMN,
      it is possible to tap the accuracy of neural sound discrimination and sensory
      memory functions. These studies have found smaller response amplitudes and longer
      latencies for speech and non-speech sound changes in children with SLI than in
      typically developing children, suggesting impaired and slow auditory
      discrimination in SLI. Furthermore, they suggest shortened sensory memory
      duration and vulnerability of the sensory memory to masking effects. Importantly,
      some studies reported associations between MMN parameters and language test
      measures. In addition, it was found that language intervention can influence the
      abnormal MMN in children with SLI, enhancing its amplitude. These results suggest
      that the MMN can shed light on the neural basis of various auditory and memory
      impairments in SLI, which are likely to influence speech perception.

PMID- 29182948
TI  - Mozart's music in children with drug-refractory epileptic encephalopathies:
      Comparison of two protocols.
AB  - In this prospective, randomized, open label study, we compared the effect on
      seizure recurrence and quality-of-life parameters, of two different protocols of
      music therapy in children and adolescents with refractory epileptic
      encephalopathies. Nine out of 19 patients (13 males and 6 females, aged between 1
      and 24years) were randomized to listen to Mozart's sonata in D major for two
      pianos K448 for 2h/day for 2weeks; other 10 children were randomized on a set of
      Mozart's compositions. In group 1 (K448), 2/9 children (22.2%) had a >=75%
      seizure decrease; two patients had less than 50% seizure reduction, and the other
      five were unchanged. In group 2 (set Mozart), 7/10 patients (70%) had a
      significant seizure reduction (specifically, >=50% in 1/10; >=75% in 4/10; 100%
      in 2/10). An overall more significant behavioral improvement including less
      irritability and tearfulness, reduced self-/heteroaggression, a better daytime
      vigilance, and nighttime sleep quality, was also reported in children from group
      2. In conclusion, the present study seems to confirm that music therapy may be an
      additional, nonpharmacological, effective treatment for patients with refractory
      epileptic seizures in childhood. The Mozart's set of different compositions can
      be better accepted and effective than the K448.

PMID- 29182950
TI  - Design, synthesis, anti-inflammatory antitumor activities, molecular modeling and
      molecular dynamics simulations of potential naprosyn(r) analogs as COX-1 and/or
      COX-2 inhibitors.
AB  - Inflammation is a fundamental physiological process that is essential for
      survival of human being but at the same time is one of the major causes of human
      morbidity and mortality. In the past decade, numerous advances have taken place
      in the understanding and development of novel anti-inflammatory drugs. Therefore,
      investigation of newest anti-inflammatory agents is still a major challenge. In
      this study, novel and successfully synthesized naproxen-derivatives indicated
      powerful anti-inflammatory properties as potent of COX-1 and/or COX-2 inhibitors
      are reported. Results obtained revealed the presence of very potent derivatives
      with% inhibition of the oedema by 100% in addition to enzyme inhibition values
      that can reach 92%. The molecular docking and molecular dynamic calculations have
      been studied. Thus, new potent candidates for further investigation as
      prospective non-steroidal anti-inflammatory drug were proposed. Furthermore,
      twenty of the synthesized derivatives have been selected by the NCI, USA for anti
      cancer screening and some of the tested compounds showed good% growth inhibition
      and some selectivity against some cell lines such as melanoma, non-small cell
      lung and colon cancer with GI% values ranging from 60.9 to 82.8%. Structure
      activity relationship has been performed and molecular modeling studies and
      molecular dynamic simulations have been performed for more explanation of the
      action of the synthesized compounds.

PMID- 29182951
TI  - The aetiology of borderline personality disorder (BPD): contemporary theories and
      putative mechanisms.
AB  - This article presents an overview of current knowledge regarding the aetiology of
      Borderline Personality Disorder (BPD). It begins with a brief synopsis of early
      research and theory, and discusses how changing conceptualisations of BPD have
      impacted on our aetiological knowledge. Contemporary theories are described and
      presented within a developmental psychopathology framework. Deficient co
      regulation and social communication in infancy are purported to underpin
      emotional dysregulation and social cognition deficits across development. These
      mechanisms are further potentiated by maladaptive social experiences in a series
      of positive feedback loops. Prospective research provides preliminary evidence
      for the reciprocal (or mediating) effects of maladaptive experiences and
      childhood dysregulation. Moving forward, cohort studies may incorporate
      neurobiological assessments to examine the biological systems underpinning
      phenotypic (e.g., impulsivity, disturbed relatedness) covariation.

PMID- 29182949
TI  - Modeling the potential health benefits of lower household air pollution after a
      hypothetical liquified petroleum gas (LPG) cookstove intervention.
AB  - INTRODUCTION: Improved biomass and advanced fuel cookstoves can lower household
      air pollution (HAP), but levels of fine particulate matter (PM2.5) often remain
      above the World Health Organization (WHO) recommended interim target of 35MUg/m3.
      METHODS: Based on existing literature, we first estimate a range of likely levels
      of personal PM2.5 before and after a liquefied petroleum gas (LPG) intervention.
      Using simulations reflecting uncertainty in both the exposure estimates and
      exposure-response coefficients, we estimate corresponding expected health
      benefits for systolic blood pressure (SBP) in adults, birthweight, and pneumonia
      incidence among children <2years old. We also estimate potential avoided
      premature mortality among those exposed. RESULTS: Our best estimate is that an
      LPG stove intervention would decrease personal PM2.5 exposure from approximately
      270MUg/m3 to approximately 70MUg/m3, due to likely continued use of traditional
      open-fire stoves. We estimate that this decrease would lead to a 5.5mmHg lower
      SBP among women over age 50, a 338g higher birthweight, and a 37% lower incidence
      of severe childhood pneumonia. We estimate that decreased SBP, if sustained,
      would result in a 5%-10% decrease in mortality for women over age 50. We estimate
      that higher birthweight would reduce infant mortality by 4 to 11 deaths per 1000
      births; for comparison, the current global infant mortality rate is 32/1000 live
      births. Reduced exposure is estimated to prevent approximately 29 cases of severe
      pneumonia per year per 1000 children under 2, avoiding approximately 2-3
      deaths/1000 per year. However, there are large uncertainties around all these
      estimates due to uncertainty in both exposure estimates and in exposure-response
      coefficients; all health effect estimates include the null value of no benefit.
      CONCLUSIONS: An LPG stove intervention, while not likely to lower exposure to the
      WHO interim target level, is still likely to offer important health benefits.

PMID- 29182953
TI  - The use of laser Doppler flowmetry to evaluate oral soft tissue blood flow in
      humans: A review.
AB  - The objective of this work is to define the conditions for improving the use of
      laser Doppler flowmetry (LDF) and to determine the limits for the use of this
      technique. This article systematically reviews the literature on the evaluation
      of oral soft tissue blood microcirculation by LDF. We analysed the available
      literature through October 2016 using the database resources Medline/PubMed, the
      Cochrane Oral Health Group Specialist Trials Register and the ISI Web of
      Knowledge. Several points emerged from this literature review The use of LDF
      involves specific constraints; however, the influence of different factors
      (temperature, tobacco, pressure etc.) must be adequately controlled when using
      LDF. LDF measurements of soft tissue within the oral cavity vary depending on the
      anatomical site. In dentistry, LDF can be used to track healing progress in
      periodontal surgery and to diagnose vascular flow changes in the connective
      tissue of mucosae covered by a removable prosthesis at an early stage prior to
      the onset of clinical inflammation signs.

PMID- 29182954
TI  - Assessment of signature handwriting evidence via score-based likelihood ratio
      based on comparative measurement of relevant dynamic features.
AB  - This paper extends on previous research on the extraction and statistical
      analysis on relevant dynamic features (width, grayscale and radian combined with
      writing sequence information) in forensic handwriting examinations. In this
      paper, a larger signature database was gathered, including genuine signatures,
      freehand imitation signatures, random forgeries and tracing imitation signatures,
      which are often encountered in casework. After applying Principle Component
      Analysis (PCA) of the variables describing the proximity between specimens, a two
      dimensional kernel density estimation was used to describe the variability of
      within-genuine comparisons and genuine-forgery comparisons. We show that the
      overlap between the within-genuine comparisons and the genuine-forgery
      comparisons depends on the imitated writer and on the forger as well. Then, in
      order to simulate casework conditions, cases were simulated by random sampling
      based on the collected signature dataset. Three-dimensional normal density
      estimation was used to estimate the numerator and denominator probability
      distribution used to compute a likelihood ratio (LR). The comparisons between the
      performance of the systems in SigComp2011 (based on static features) and the
      method presented in this paper (based on relevant dynamic features) showed that
      relevant dynamic features are better than static features in terms of accuracy,
      false acceptance rate, false rejection rate and calibration of likelihood ratios.

PMID- 29182952
TI  - Building stereotypic connectivity: mechanistic insights into structural
      plasticity from C. elegans.
AB  - The ability of neurons to modify or remodel their synaptic connectivity is
      critical for the function of neural circuitry throughout the life of an animal.
      Understanding the mechanisms underlying neuronal structural changes is central to
      our knowledge of how the nervous system is shaped for complex behaviors and how
      it further adapts to developmental and environmental demands. Caenorhabditis
      elegans provides a powerful model for examining developmental processes and for
      discovering mechanisms controlling neural plasticity. Recent findings have
      identified conserved themes underlying neural plasticity in development and under
      environmental stress.

PMID- 29182955
TI  - Individual human scent as a forensic identifier using mantrailing.
AB  - Specially trained dogs have long been used by law enforcement agencies to help in
      criminal investigations and in searching for missing persons. Still, it is
      unclear which components of human scent released into the environment contribute
      to successful searches of individuals. In this study, saliva and axillary sweat
      samples were taken from a total of 190 people. Additionally, DNA was extracted
      from whole blood of seven different people and used as an odour sample as well.
      Overall 675 tests (trails) were performed during a period of 18 months. The
      ability to track individuals with the odour samples mentioned above was examined
      with seven dogs, four of which were specially-trained dogs (mantrailer) from the
      Saxony Police. Results indicated that specially-trained police dogs can track a
      person with an average success rate of 82% and correctly identify the absence of
      an odour track with an average success rate of 97% under various conditions.
      Private rescue dogs were less successful with an average success rate of 65% and
      75% respectively. These data suggest that the potential error rate of a well
      trained handler team is low and can be a useful tool for law enforcement
      personnel. Saliva, as a reference odour source, was found to be particularly
      suitable for the search. The results of the study suggest that the components
      contained in axillary sweat, saliva and DNA extracted from whole blood are
      sufficient, serving as a key stimulus for individualized searches.

PMID- 29182956
TI  - Unintentional mortality associated with paracetamol and codeine preparations,
      with and without doxylamine, in Australia.
AB  - INTRODUCTION: Misuse of paracetamol, codeine and doxylamine combination
      analgesics may lead to addiction and mortality. This study aimed to (1) identify
      unintentional deaths in Australia associated with use of combination analgesic
      products containing paracetamol, codeine and doxylamine; (2) describe cases
      characteristics, including demographics and additional medication use; and (3)
      identify common factors associated with misuse and mortality of these medicines
      in Australia. DESIGN: This retrospective case series analysed National Coronial
      Information System data to identify cases of unintentional death attributable to
      paracetamol, codeine and doxylamine products between 2002 and 2012. SETTING:
      Three Eastern Australian states: New South Wales, Queensland, Victoria,
      comprising a population of approximately 18.6 million people. RESULTS: 441
      unintentional deaths attributed to paracetamol/codeine products were identified;
      doxylamine was detected in 102 cases (23%). Overall unintentional death rates
      rose from 0.9-per-million in 2002 to 3.6-per-million in 2009, declining to 1.9
      per-million in 2012. Median age at time of death was 48, half of all cases
      occurred between 35-54 years of age, and 57% were female. Concomitant medication
      use was detected in 79% of cases, including benzodiazepines, other opioids,
      psychiatric medications, alcohol and illicit drugs. Behaviours consistent with
      drug misuse including doctor/pharmacy shopping, excessive dosages and extended
      use, were identified in 24% of cases. CONCLUSIONS: This study identified 441
      deaths associated with codeine-combination analgesic products across three
      Australian states; with an average of 40 deaths per year. Death commonly involved
      multiple substance use and abuse behaviours indicative of misuse and dependence.

PMID- 29182957
TI  - Ankle fracture - Correlation of Lauge-Hansen classification and patient reported
      fracture mechanism.
AB  - INTRODUCTION: The genetic Lauge-Hansen classification is used for reconstruction
      of the mechanism of ankle injury. In this study, we addressed the question of
      agreement between the mechanism of the fracture as postulated by the Lauge-Hansen
      classification and mechanism reported by the patient in rotational ankle
      fractures. MATERIAL AND METHODS: Radiographs of 78 patients with acute malleolar
      fractures were analyzed and compared with fracture mechanisms reported by these
      patients. RESULTS: The patient reported mechanisms were in concordance with the
      mechanism deducted from the X-rays in 49% of cases. Only 17% of patients who
      recalled a pronation trauma actually had radiographs classified as pronation
      fractures while 76% of patients who recalled a supination trauma were also
      radiographically classified as having sustained supination type fractures.
      CONCLUSION: The Lauge-Hansen classification should be used with caution for
      determining the actual mechanism of injury as it was able to predict the patient
      reported fracture mechanism in less than 50% of cases. A substantial percentage
      of fractures appearing radiographically as supination type injuries may have been
      actually produced by a pronation fracture mechanism.

PMID- 29182958
TI  - Vitamin A and marbling attributes: Intramuscular fat hyperplasia effects in
      cattle.
AB  - Twenty Angus steers were fed a diet low in beta-carotene and vitamin A for
      10months. Ten steers were supplemented with vitamin A weekly, while the other ten
      steers did not receive any additional vitamin A. The results demonstrated that
      the restriction of vitamin A intake increased intramuscular fat (IMF) by 46%.
      This was a function of the total number of marbling flecks increasing by 22% and
      the average marbling fleck size increasing by 14%. Vitamin A restriction resulted
      in marbling flecks that were less branched (22%) and slightly more round (4%)
      with an increased minor axis length (7%). However, restricting vitamin A did not
      affect the size of the intramuscular or subcutaneous adipocyte cells or the
      subcutaneous fat depth. The results suggest that vitamin A affects the amount of
      marbling and other attributes of the marbling flecks due to hyperplasia rather
      than hypertrophy. This may explain why vitamin A restriction specifically affects
      IMF rather than subcutaneous fat deposition.

PMID- 29182959
TI  - Social biases modulate the loss of redundant forms in the cultural evolution of
      language.
AB  - According to the competitive exclusion principle (Gause, 1934), competition for
      the same niche must eventually lead one competitor to extinction or the
      occupation of a new niche. This principle applies in both biology and the
      cultural evolution of language, where different words and structures compete for
      the same function or meaning (Aronoff, 2016). Across languages, for example, word
      order trades off with case marking as a means of indicating who did what to whom
      in a sentence. Previous experimental work has shed light on how such trade-offs
      come about as languages adapt to human biases through learning and production,
      with biases becoming amplified through iterated learning over generations. At the
      same time, a large body of work has documented the impact of social biases on
      language change. However, little work has investigated how social biases interact
      with learning and production biases. In particular, the social dimension of
      language may provide alternative niches for otherwise redundant forms, preventing
      or slowing their extinction. We tested this hypothesis in an iterated-learning
      experiment in which participants were exposed to a language with two dialects,
      both of which had fixed word order, but differed in whether they employed case
      markers. In one condition, we biased participants socially towards speakers of
      the dialect that employed case; in other conditions we provided no bias, or
      biased participants for or against the dialect without case. As expected under
      our hypothesis, the use of case markers declined over time in all conditions, but
      the social bias in favor of case-dialect speakers slowed the decline.

PMID- 29182960
TI  - Targeted drug delivery for tumor therapy inside the bone marrow.
AB  - Bone marrow is the primary hematopoietic organ, which is involved in multiple
      malignant diseases including acute and chronic leukemia, multiple myeloma,
      myelodysplastic syndromes, and bone metastases from solid tumors. These
      malignancies affect normal homeostasis and reshape the bone marrow
      microenvironment. There are limited treatment options for them because of their
      inevitable aggravation. The current systemic administration of anticancer agents
      is difficult to achieve ideal therapeutic dose to suppress tumor growth at bone
      marrow diseased sites, and is always associated with a high incidence of relapse
      and severe side effects. The limitations of current treatments urge scientists to
      develop bone marrow targeted drug delivery systems intended for the treatment of
      diseased bone marrow, which can improve the efficacy of therapeutic agents and
      reduce their dose-limiting systemic side effects on healthy tissues. In this
      review we first present the current opinions on bone marrow vasculature, as well
      as the molecular and structural interactions between tumor cells and the diseased
      bone marrow. In the second part, we highlight the different design rationales and
      strategies of bone marrow delivery systems and their therapeutic applications for
      the treatment of malignancies inside the bone marrow.

PMID- 29182961
TI  - Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro
      and in vivo: Role of DNA methyltransferase 1.
AB  - Cells perceive the physical cues such as perturbations of extracellular matrix
      (ECM) stiffness, and translate these stimuli into biochemical signals controlling
      various aspects of cell behavior, which contribute to the physiological and
      pathological processes of multiple organs. In this study, we tested the
      hypothesis that during arterial stiffening, vascular smooth muscle cells (SMCs)
      sense the increase of ECM stiffness, which modulates the cellular phenotype
      through the regulation in DNA methyltransferases 1 (DNMT1) expression. Moreover,
      we hypothesized that the mechanisms involve intrinsic stiffening and deficiency
      in contractility of vascular SMCs. Substrate stiffening was mimicked in vitro
      with polyacrylamide gels. A contractile-to-synthetic phenotypic transition was
      induced by substrate stiffening in vascular SMCs through the down-regulation of
      DNMT1 expression. DNMT1 repression was also observed in the tunica media of mice
      aortas in an acute aortic injury model and a chronic kidney failure model, as
      well as in the tunica intima of human carotid arteries with calcified
      atherosclerotic lesions. DNMT1 inhibition facilitates arterial stiffening in vivo
      and promotes osteogenic transdifferentiation, calcification and cellular
      stiffening of vascular SMCs in vitro. These effects may be attributable, at least
      in part, to the role of DNMT1 in regulating the promoter activities of Transgelin
      (SM22alpha) and alpha-smooth muscle actin (SMA) and the functional contractility
      of SMCs. We conclude that DNMT1 is a critical regulator that negatively regulates
      arterial stiffening via maintaining the contractile phenotype of vascular SMCs.
      This research may facilitate elucidation of the complex crosstalk between
      vascular SMCs and their surrounding matrix in healthy and in pathological
      conditions and provide new insights into the implications for potential targeting
      of the phenotypic regulatory mechanisms in material-related therapeutic
      applications.

PMID- 29182962
TI  - The possible worlds of global health research: An ethics-focused discourse
      analysis.
AB  - Representations of the world enable global health research (GHR), discursively
      constructing sites in which studies can legitimately take place. Depoliticized
      portrayals of the global South frequently obscure messy legacies of colonialism
      and motivate technical responses to health problems with political and economic
      root causes. Such problematic representations of the world have not yet been
      rigorously examined in relation to global health ethics, a major site of
      scholarly effort towards GHR that promotes justice and fairness. We carried out a
      discourse analysis of four guidance documents relevant to the ethical practice of
      GHR, purposively selecting texts covering different genres (UN documents and
      journal articles) and prominent GHR foci (HIV and clinical trials). In light of
      increasing acknowledgement of the lessons Indigenous health scholarship holds for
      global health ethics, the four analyzed texts also included a set of principles
      developed to support Indigenous nation-building. Three of four documents featured
      global disparities as reasons for ethical caution. These inequalities appeared
      without explanation or causes, with generation of new scientific knowledge
      following as a logical response to such disparities. The fourth - Indigenous
      health-focused - document clearly identified 'colonialism' as a reason for both
      inequities in society, and related harmful research practices. Solutions to
      disparities in this text did not necessarily involve cutting-edge research, but
      focused instead on empowerment and responsiveness to community priorities and
      needs. These contrasting representations of the world were accomplished in ways
      that depended on texts' 'participants', or the people they represented; specific
      vocabularies or language usages; intertextual relationships to prior texts; and
      overall objectives or intentions of the author(s). Our results illustrate how
      ethics and other guidance documents serve as an important terrain for
      constructing, naturalizing or contesting problematic representations of the world
      of GHR.

PMID- 29182963
TI  - Female garment workers' experiences of violence in their homes and workplaces in
      Bangladesh: A qualitative study.
AB  - The ways in which women's engagement in paid work shapes their experiences of
      violence in the home and workplace is widely debated, particularly in Bangladesh,
      but rarely considered together. We undertook 23 in-depth interviews with female
      garment workers living in slums in Bangladesh, and nine interviews with key
      informants (factory managers and supervisors, male workers, and employees from
      non-governmental organisations). Data came from two studies conducted in Dhaka,
      Bangladesh - the first between August and September 2011 and the second between
      June and August 2015 - and were analysed using thematic analysis. In both
      settings, women experienced similar forms of violence, including emotional,
      physical, sexual, and economic, although from different perpetrators. Despite
      violence in the home and violence in the workplace typically being considered
      separately, we identify four overlaps between them. First, violence in both
      settings is shaped by how patriarchal norms and structures of institutions
      intersect with institutions economic structures. Second, dominant representations
      of female garment workers as sex workers or sexually promiscuous enables violence
      against them. Third, economic violence is used as a way to control and limit
      women's autonomy. Fourth, women develop strategies to continue working and
      maximize the benefits of work for themselves. Finally, we suggest how
      interventions could work to prevent violence in the home and workplace.

PMID- 29182964
TI  - Mass release curves as the constitutive curves for modeling diffusive transport
      within biological tissue.
AB  - In diffusion governed by Fick's law, the diffusion coefficient represents the
      phenomenological material parameter and is, in general, a constant. In certain
      cases of diffusion through porous media, the diffusion coefficient can be
      variable (i.e. non-constant) due to the complex process of solute displacements
      within microstructure, since these displacements depend on porosity, internal
      microstructural geometry, size of the transported particles, chemical nature, and
      physical interactions between the diffusing substance and the microstructural
      surroundings. In order to provide a simple and general approach of determining
      the diffusion coefficient for diffusion through porous media, we have introduced
      mass release curves as the constitutive curves of diffusion. The mass release
      curve for a selected direction represents cumulative mass (per surface area)
      passed in that direction through a small reference volume, in terms of time. We
      have developed a methodology, based on numerical Finite Element (FE) and
      Molecular Dynamics (MD) methods, to determine simple mass release curves of
      solutes through complex media from which we calculate the diffusion coefficient.
      The diffusion models take into account interactions between solute particles and
      microstructural surfaces, as well as hydrophobicity (partitioning). We illustrate
      the effectiveness of our approach on several examples of complex composite media,
      including an imaging-based analysis of diffusion through pancreatic cancer
      tissue. The presented work offers an insight into the role of mass release curves
      in describing diffusion through porous media in general, and further in case of
      complex composite media such as biological tissue.

PMID- 29182965
TI  - Real-time continuous recognition of knee motion using multi-channel
      mechanomyography signals detected on clothes.
AB  - Mechanomyography (MMG) signal has been recently investigated for pattern
      recognition of human motion. In theory, it is no need of direct skin contact to
      be detected and unaffected by changes in skin impedance. So, it is hopeful for
      developing wearable sensing device with clothes. However, there have been no
      studies so far to detect MMG signal on clothes and verify the feasibility of
      pattern recognition. For this study, 4-channel MMG signals were detected on
      clothes from the thigh muscles of 8 able-bodied participants. The support vector
      machines (SVM) classifier with 4 common features was used to recognize 6 knee
      motions and the average accuracy of nearly 88% was achieved. The accuracy can be
      further improved up to 91% by introducing a new proposed feature of the
      difference of mean absolute value (DMAV), but not by root mean square (RMS) or
      mean absolute value (MAV). Furthermore, the first-order Markov chain model was
      combined with the SVM classifier and it can avoid the misclassifications in some
      cases. For application to wearable power-assisted devices, this study would
      promote the developments of more flexible, more comfortable, and minimally
      obtrusive wearable sensing devices with clothes and recognition techniques of
      human motion intention.

PMID- 29182966
TI  - Sustained effects of volcanic ash on biofilm stoichiometry, enzyme activity and
      community composition in North- Patagonia streams.
AB  - Volcanic eruptions are extreme perturbations that affect ecosystems. These events
      can also produce persistent effects in the environment for several years after
      the eruption, with increased concentrations of suspended particles and the
      introduction of elements in the water column. On 4th June 2011, the Puyehue
      Cordon Caulle Volcanic Complex (40.59 degrees S-72.11 degrees W, 2200m.a.s.l.)
      erupted explosively in southern Chile. The area affected by the volcano was
      devastated; a thick layer of volcanic ash (up to 30cm) was deposited in areas 50
      km east of the volcano towards Argentina. The aim of the present study was to
      evaluate the effect of volcanic ash deposits on stream ecosystems four years
      after the eruption, comparing biofilm stoichiometry, alkaline phosphatase
      activity, and primary producer's assemblage in streams which were severely
      affected by the volcano with unaffected streams. We confirmed in the laboratory
      that ash deposited in the catchment of affected streams still leach phosphorus
      (P) into the water four years after eruption. Results indicate that affected
      streams still receive volcanic particles and that these particles release P, thus
      stream water exhibits high P concentration. Biofilm P content was higher and the
      C:P ratio lower in affected streams compared to unaffected streams. As a
      consequence of less P in unaffected streams, the alkaline phosphatase activity
      was higher compared to affected streams. Cyanobacteria increased their abundances
      (99.9% of total algal biovolume) in the affected streams suggesting that the
      increase in P may positively affect this group. On the contrary, unaffected
      streams contained a diatom dominant biofilm. In this way, local heterogeneity was
      created between sub-catchments located within 30 km of each other. These types of
      events should be seen as opportunities to gather valuable ecological information
      about how severe disturbances, like volcanic eruptions, shape landscapes and
      lotic systems for several years after the event.

PMID- 29182967
TI  - The relationships between leaf economics and hydraulic traits of woody plants
      depend on water availability.
AB  - Leaf economics and hydraulic traits are simultaneously involved in the process of
      trading water for CO2, but the relationships between these two suites of traits
      remain ambiguous. Recently, Li et al. (2015) reported that leaf economics and
      hydraulic traits were decoupled in five tropical-subtropical forests in China. We
      tested the hypothesis that the relationships between economics and hydraulic
      traits may depend on water availability. We analysed five leaf economics traits,
      four hydraulic traits and anatomical structures of 47 woody species on the Loess
      Plateau with poor water availability and compared those data with Li et al.
      (2015) obtained in tropical-subtropical regions with adequate water. The results
      showed that plants on the Loess Plateau tend to have higher leaf tissue density
      (TD), leaf nitrogen concentrations and venation density (VD) and lower stomatal
      guard cell length (SL) and maximum stomatal conductance to water vapour (gwmax).
      VD showed positive correlations with leaf nitrogen concentrations, palisade
      tissue thickness (PT) and ratio of palisade tissue thickness to spongy tissue
      thickness (PT/ST). Principal component analysis (PCA) showed a result opposite
      from those of tropical-subtropical regions: leaf economics and hydraulic traits
      were coupled on the Loess Plateau. A stable correlation between these two suites
      of traits may be more cost-effective on the Loess Plateau, where water
      availability is poor. The correlation of leaf economics and hydraulic traits may
      be a type of adaptation mechanism in arid conditions.

PMID- 29182968
TI  - Testing the toxicity of metals, phenol, effluents, and receiving waters by root
      elongation in Lactuca sativa L.
AB  - Phytotoxicity tests using higher plants are among the most simple, sensitive, and
      cost-effective of the methods available for ecotoxicity testing. In the present
      study, a hydroponic-based phytotoxicity test using seeds of Lactuca sativa was
      used to evaluate the water quality of receiving waters and effluents near two
      industrial sites (Soyo and Daejon) in Korea with respect to the toxicity of 10
      metals (As, Cd, Cr, Cu, Fe, Pb, Mn, Hg, Ni, Zn) and phenol, and of the receiving
      waters and effluents themselves. First, the L. sativa hydroponic bioassay was
      used to determine whether the receiving water or effluents were toxic; then, the
      responsible toxicant was identified. The results obtained with the L. sativa
      bioassay ranked the EC50 toxicities of the investigated metal ions and phenol as:
      Cd > Ni > Cu > Zn > Hg > phenol > As > Mn > Cr > Pb > Fe. We found that Zn was
      the toxicant principally responsible for toxicity in Daejeon effluents. The
      Daejeon field effluent had a higher Zn concentration than permitted by the
      effluent discharge criteria of the Ministry of Environment of Korea. Our
      conclusion on the importance of Zn toxicity was supported by the results of the
      L. sativa hydroponic assay, which showed that the concentration of Zn required to
      inhibit root elongation in L. sativa by 50% (EC50) was higher in the Daejeon
      field effluent than that of pure Zn. More importantly, we proved that the L.
      sativa hydroponic test method can be applied not only as an alternative tool for
      determining whether a given waste is acceptable for discharge into public water
      bodies, but also as an alternative method for measuring the safety of aquatic
      environments using EC20 values, with respect to the water pollutants investigated
      (i.e., Cd, Cr, Cu, Pb, Mn, Hg, Ni, Zn, and phenol).

PMID- 29182969
TI  - Simulated developmental and reproductive impacts on amphibian populations and
      implications for assessing long-term effects.
AB  - Fish endpoints measured in early life stage toxicity tests are often used as
      representative of larval amphibian sensitivity in Ecological Risk Assessment
      (ERA). This application potentially overlooks the impact of developmental delays
      on amphibian metamorphosis, and thereby reduced survival, in amphibian
      populations constrained by habitat availability. Likewise, the effects of reduced
      productivity or altered sexual development as a result of chemical exposure are
      not presented in terms of lower population fecundity in these surrogate tests.
      Translating endpoints measured in toxicity tests to those that are more
      representative of amphibian ecology and population dynamics provides a means of
      identifying how developmental effects result in long-term impacts. Here we
      compare effects of developmental delay on metamorphosis success in six anuran
      species and simulate population-level impacts of subsequent reductions in larval
      survival as well as potential reductions in fecundity as a result of
      developmental impacts. We use deterministic matrix models to compare realistic
      combinations of amphibian demographic rates and relative impacts of reduced
      growth on larval survival and subsequently on population growth. Developmental
      delays are less detrimental in species with longer and less synchronous larval
      periods. All six species were most sensitive to changes in first-year survival,
      and damping ratios were generally a good indicator of resilience to perturbations
      in both larval survival and fecundity. Further identification of species and
      population-level vulnerabilities can improve the evaluation of sublethal effects
      in relevant context for ERA.

PMID- 29182970
TI  - Time to continuous electroencephalogram in repeated admissions to the pediatric
      intensive care unit.
AB  - PURPOSE: Describe timing from intensive care unit (ICU) admission to initiation
      of continuous electroencephalogram (cEEG) in repeated ICU admissions. METHOD: We
      performed a retrospective observational study in pediatric patients who underwent
      repeated ICU admissions with cEEG from 2011 to 2013. The main outcome measure was
      time from ICU admission to cEEG. RESULTS: There were 41 patients (54% males) with
      at least 2 ICU admissions with cEEG (median (p25-p75) age at first admission: 3.3
      (0.3-8.4) years, at second admission: 3.9 (1.1-9.4) years), 7 patients (57%
      males, 9.9 (2.9-11.5) years) with at least 3 ICU admissions, and 5 patients (60%
      males, 10.1 (4-10.5) years) with at least 4 ICU admissions. One patient had 21
      ICU admissions. The median (p25-p75) time from ICU admission to cEEG was not
      different during the first and second ICU admissions [10.7 (1.9-22.9) hours
      versus 13 (0.2-36.7) hours; p=0.908]. Among patients with electrographic seizures
      on first admission, time to cEEG was not different during the first and second
      admissions [7.9 (0.5-23.4) hours versus 14.5 (-2 to 44.5) hours; p=0.636]. Among
      patients with status epilepticus during the first admission, time to cEEG was not
      different between the first and second admissions [15.3 (9-79) hours versus 40.7
      (19.3-42.6) hours; p=0.75]. CONCLUSIONS: The time from ICU admission to the
      initiation of cEEG did not decrease in second or subsequent ICU admissions, even
      in patients with seizures or status epilepticus on the first admission.

PMID- 29182971
TI  - Detection and attribution of nitrogen runoff trend in China's croplands.
AB  - Reliable detection and attribution of changes in nitrogen (N) runoff from
      croplands are essential for designing efficient, sustainable N management
      strategies for future. Despite the recognition that excess N runoff poses a risk
      of aquatic eutrophication, large-scale, spatially detailed N runoff trends and
      their drivers remain poorly understood in China. Based on data comprising 535
      site-years from 100 sites across China's croplands, we developed a data-driven
      upscaling model and a new simplified attribution approach to detect and attribute
      N runoff trends during the period of 1990-2012. Our results show that N runoff
      has increased by 46% for rice paddy fields and 31% for upland areas since 1990.
      However, we acknowledge that the upscaling model is subject to large
      uncertainties (20% and 40% as coefficient of variation of N runoff,
      respectively). At national scale, increased fertilizer application was identified
      as the most likely driver of the N runoff trend, while decreased irrigation
      levels offset to some extent the impact of fertilization increases. In southern
      China, the increasing trend of upland N runoff can be attributed to the growth in
      N runoff rates. Our results suggested that increased SOM led to the N runoff rate
      growth for uplands, but led to a decline for rice paddy fields. In combination,
      these results imply that improving management approaches for both N fertilizer
      use and irrigation is urgently required for mitigating agricultural N runoff in
      China.

PMID- 29182973
TI  - Diet-specific trophic transfer of mercury in tilapia (Oreochromis niloticus):
      Biodynamic perspective.
AB  - This study tested the hypothesis that different diets could modulate mercury (Hg)
      trophic transfer by concurrently altering the transfer of energy (in terms of
      growth) and transfer of Hg (in terms of biodynamic process). Firstly, we
      conducted a 40-d laboratory bioaccumulation experiment, in which tilapia
      (Oreochromis niloticus) was exposed to inorganic mercury (Hg[II]) and
      methylmercury (MeHg) via feeding on three distinct diets (macrophyte, freshwater
      shrimp, and commercial pellets) at a fixed ingestion rate of 0.065 g g-1 d-1.
      During the dietary exposure period, tilapia exhibited Hg species- and diet
      dependent Hg trophic transfer patterns and diet-specific growth rates. We then
      employed a biokinetic model to assess how diet-specific biodynamics and/or diet
      specific growth rates modulated the overall Hg bioaccumulation and trophic
      transfer. The diet-specific assimilation efficiencies (AEs) were monitored using
      radioisotope technique, and the determined AEs of Hg(II) (8.6%-29.7%) varied by
      3.5 times among diets whereas the MeHg AEs (94.4%-97.1%) were not affected. The
      biokinetic modeling further revealed that Hg(II) trophic transfer in tilapia was
      controlled by the diet-specific AEs, while MeHg trophic transfer was governed by
      the diet-specific growth rates. Specifically, a diet-derived high growth rate
      reduced the MeHg trophic transfer in pellets-fed tilapia, and the overall
      accumulated MeHg level in fish was under the control of both somatic growth
      dilution and dietary MeHg influx. Moreover, we observed that the Hg levels
      (mainly as MeHg) in fast-growing farmed tilapia were significantly lower than
      wild-living tilapia after 100 d exposure in the field, attributed to somatic
      growth dilution (SGD). Both the laboratory and field study therefore demonstrated
      the importance of diet-derived SGD in modulating mercury trophic transfer in
      aquatic food webs.

PMID- 29182972
TI  - Endocrine disruption and differential gene expression in sentinel fish on St.
      Lawrence Island, Alaska: Health implications for indigenous residents.
AB  - People living a subsistence lifestyle in the Arctic are highly exposed to
      persistent organic pollutants, including polychlorinated biphenyls (PCBs).
      Formerly Used Defense (FUD) sites are point sources of PCB pollution; the Arctic
      contains thousands of FUD sites, many co-located with indigenous villages. We
      investigated PCB profiles and biological effects in freshwater fish (Alaska
      blackfish [Dallia pectoralis] and ninespine stickleback [Pungitius pungitius])
      living upstream and downstream of the Northeast Cape FUD site on St. Lawrence
      Island in the Bering Sea. Despite extensive site remediation, fish remained
      contaminated with PCBs. Vitellogenin concentrations in males indicated exposure
      to estrogenic contaminants, and some fish were hypothyroid. Downstream fish
      showed altered DNA methylation in gonads and altered gene expression related to
      DNA replication, response to DNA damage, and cell signaling. This study
      demonstrates that, even after site remediation, contaminants from Cold War FUD
      sites in remote regions of the Arctic remain a potential health threat to local
      residents - in this case, Yupik people who had no influence over site selection
      and use by the United States military.

PMID- 29182974
TI  - Suspect screening and non-targeted analysis of drinking water using point-of-use
      filters.
AB  - Monitored contaminants in drinking water represent a small portion of the total
      compounds present, many of which may be relevant to human health. To understand
      the totality of human exposure to compounds in drinking water, broader monitoring
      methods are imperative. In an effort to more fully characterize the drinking
      water exposome, point-of-use water filtration devices (Brita(r) filters) were
      employed to collect time-integrated drinking water samples in a pilot study of
      nine North Carolina homes. A suspect screening analysis was performed by matching
      high resolution mass spectra of unknown features to molecular formulas from EPA's
      DSSTox database. Candidate compounds with those formulas were retrieved from the
      EPA's CompTox Chemistry Dashboard, a recently developed data hub for
      approximately 720,000 compounds. To prioritize compounds into those most relevant
      for human health, toxicity data from the US federal collaborative Tox21 program
      and the EPA ToxCast program, as well as exposure estimates from EPA's ExpoCast
      program, were used in conjunction with sample detection frequency and abundance
      to calculate a "ToxPi" score for each candidate compound. From ~15,000 molecular
      features in the raw data, 91 candidate compounds were ultimately grouped into the
      highest priority class for follow up study. Fifteen of these compounds were
      confirmed using analytical standards including the highest priority compound, 1,2
      Benzisothiazolin-3-one, which appeared in 7 out of 9 samples. The majority of the
      other high priority compounds are not targets of routine monitoring, highlighting
      major gaps in our understanding of drinking water exposures. General product-use
      categories from EPA's CPCat database revealed that several of the high priority
      chemicals are used in industrial processes, indicating the drinking water in
      central North Carolina may be impacted by local industries.

PMID- 29182975
TI  - Adverse events of Dupilumab in adults with moderate-to-severe atopic dermatitis:
      A meta-analysis.
AB  - BACKGROUND: Dupilumab, a fully human monoclonal antibody against interleukin-4
      receptor alpha, inhibits the signals of interleukin-4 and interleukin-13, and has
      also shown significant efficacy in patients with moderate-to-severe atopic
      dermatitis (AD), while the effect of it on adverse events remains controversial.
      OBJECTIVE: To assess the influence of dupilumab on adverse events in adults with
      moderate-to-severe AD. METHOD: Randomised controlled trials (RCTs) that compared
      dupilumab with a placebo for patients with moderate-to-severe AD were searched in
      the MEDLINE, EMBASE, Web of Science and Cochrane databases. The outcome of the
      study was the incidence of adverse events during the observation period. RESULTS:
      Eight RCTs were analysed in this study. Meta-analysis showed that patients
      treated with dupilumab had a lower risk of skin infection (risk ratio [RR] 0.54;
      95% confidence interval [CI] 0.42-0.69) and exacerbation of AD (RR 0.44, 95% CI
      0.34-0.59), but had a higher risk of injection-site reaction (RR 2.24, 95% CI
      1.68-2.99), headache (RR 1.47, 95% CI 1.05-2.06), and conjunctivitis (RR 2.64,
      95% CI 1.79-3.89) than did patients treated with a placebo. Nasopharyngitis,
      urinary tract infection, upper respiratory tract infection, and herpes virus
      infection were found balanced in dupilumab groups and placebo groups. CONCLUSION:
      Dupilumab moderately reduced the risk of skin infection and the exacerbation of
      AD, slightly increased the risk of headache, and moderately increased the risk of
      injection-site reaction and conjunctivitis, but had little effect on other
      infections in adults with moderate-to-severe AD.

PMID- 29182976
TI  - Comparison of trailside degradation across a gradient of trail use in the Sonoran
      Desert.
AB  - As recreational visitation to the Sonoran Desert increases, the concern of
      scientists, managers and advocates who manage its natural resources deepens.
      Although many studies have been conducted on trampling of undisturbed vegetation
      and the effects of trails on adjacent plant and soil communities, little such
      research has been conducted in the arid southwest. We sampled nine 450-m trail
      segments with different visitation levels in Scottsdale's McDowell Sonoran
      Preserve over three years to understand the effects of visitation on soil
      erosion, trailside soil crusts and plant communities. Soil crust was reduced by
      27-34% near medium and high use trails (an estimated peak rate of 13-70 visitors
      per hour) compared with control plots, but there was less than 1% reduction near
      low use trails (peak rate of two to four visitors per hour). We did not detect
      soil erosion in the center 80% of the trampled area of any of the trails. The
      number of perennial plant species dropped by less than one plant species on
      average, but perennial plant cover decreased by 7.5% in trailside plots compared
      with control plots 6 m off-trail. At the current levels of visitation, the
      primary management focus should be keeping people on the originally constructed
      trail tread surface to reduce impact to adjacent soil crusts.

PMID- 29182977
TI  - Decentralised black water treatment by combined auto-thermal aerobic digestion
      and ammonia - A pilot study optimising treatment capacity.
AB  - Partial heating of black water by auto-thermal aerobic digestion was combined
      with the addition of 1% w/w urea and monitoring of pathogens and indicator
      organisms over a 21-day period. After initial mixing, the 160 m3 black water (60
      m3 heated and 100 m3 non-heated) was left undisturbed. The urea was confirmed to
      be fully degraded into ammonia (5.1 g N L-1) first after 14 days, while the pH
      stabilised at around 9.2 after one week. The initial temperature of 17  degrees C
      fell by 6  degrees C during the study. E. coli and Salmonella spp., which are
      sensitive to ammonia, were inactivated during the first few days of the study,
      despite the urea only being partly hydrolysed. At day 14, f-RNA bacteriophages
      could also no longer be detected. The more persistent somatic coliphages,
      Enterococcus spp. and Ascaris eggs, showed significant but slow inactivation. The
      treatment proved to be efficient with regards to salmonella, which is a target
      pathogen in the Swedish context, but for parasite egg inactivation a higher
      temperature was required. The treatment would benefit from more frequent stirring
      to speed up the hydrolysis of urea and thus improve treatment efficiency. The
      alternative treatment scheme could increase capacity by 2.4 times, albeit with a
      40% higher cost per volume due to the increased use of urea.

PMID- 29182978
TI  - Investigation of electrodialysis anti-fouling configuration for desalting and
      treating tannery unhairing wastewater: Feasibility of by-products recovery and
      water recycling.
AB  - The desalination and treatment of tannery unhairing wastewater by electrodialysis
      (ED) is investigated in this research in order to separate, concentrate, recover
      and reuse low molecular weight charged species (S2-, HS-, OH-, Cl-, Ca2+, Na+ and
      amino acids), and to separate proteins and recycle treated water. Therefore, a
      novel electrodialysis membrane configuration was proposed. This was based on a
      double anti-fouling membrane. The ED anion exchange membrane (AEM), which is very
      sensitive to organic fouling, was protected by an ultra filtration membrane
      impermeable to the negatively charged proteins that could not reach the AEM
      surface. The experimental results were quite promising, and in spite of only one
      desalination compartment ED cell; the demineralization efficiency was 56 +/-
      1.25% (5.5-2.4 mS/cm), with a sensitive removal of sulphide, calcium and
      chloride. The organic matter (protein, peptides...) was isolated in the dilute
      compartment. The most important result was the total absence of membrane fouling.
      The experimental results remarkably proved the initial hypothesis, and suggested
      promising solutions for industrial pollution, where the membrane processes have
      never been successful.

PMID- 29182979
TI  - An atmospheric vulnerability assessment framework for environment management and
      protection based on CAMx.
AB  - This paper presents an atmospheric vulnerability assessment framework based on
      CAMx that should be helpful to assess potential impacts of changes in human,
      atmospheric environment, and social economic elements of atmospheric
      vulnerability. It is also a useful and effective tool that can provide policy
      guidance for environmental protection and management to reduce the atmospheric
      vulnerability. The developed framework was applied to evaluate the atmospheric
      environment vulnerability of 13 cities in the Beijing-Tianjin-Hebei (BTH) region
      for verification. The results indicated that regional disparity of the
      atmospheric vulnerability existed in the study site. More specifically, the
      central and southern regions show more atmospheric environment vulnerability than
      the northern regions. The impact factors of atmospheric environment vulnerability
      in the BTH region mainly derived from increasing population press, frequently
      unfavorable meteorological conditions, extensive economic growth of secondary
      industry, increased environmental pollution, and accelerating population aging.
      The framework shown in this paper is an interpretative and heuristic tool for a
      better understanding of atmospheric vulnerability. This framework can also be
      replicated at different spatial and temporal scales using context-specific
      datasets to straightly support environmental managers with decision-making.

PMID- 29182980
TI  - The influence of perforation of foil reactors on greenhouse gas emission rates
      during aerobic biostabilization of the undersize fraction of municipal wastes.
AB  - The opinion, that the use of foil reactors for the aerobic biostabilization of
      municipal wastes is not a valid method, due to vulnerability to perforation, and
      risk of uncontrolled release of exhaust gasses, was verified. This study aimed to
      determine the intensity of greenhouse gas (GHG) emissions to the atmosphere from
      the surface of foil reactors in relation to the extent of foil surface
      perforation. Three scenarios were tested: intact (airtight) foil reactor,
      perforated foil reactor, and torn foil reactor. Each experimental variant was
      triplicated, and the duration of each experiment cycle was 5 weeks. Temperature
      measurements demonstrated a significant decrease in temperature of the
      biostabilization in the torn reactor. The highest emissions of CO2, CO and SO2
      were observed at the beginning of the process, and mostly in the torn reactor.
      During the whole experiment, observed emissions of CO, H2S, NO, NO2, and SO2 were
      at a very low level which in extreme cases did not exceed 0.25 mg t-1.h-1
      (emission of gasses mass unit per waste mass unit per unit time). The lowest
      average emissions of greenhouse gases were determined in the case of the intact
      reactor, which shows that maintaining the foil reactors in an airtight condition
      during the process is extremely important.

PMID- 29182981
TI  - Evolution of various fractions during the windrow composting of chicken manure
      with rice chaff.
AB  - Different fractions during the 85-day windrow composting were characterized based
      on various parameters, such as physiochemical properties and hydrolytic enzyme
      activities; several technologies were used, including spectral scanning
      techniques, confocal laser scanning microscopy (CLSM) and 13C Nuclear Magnetic
      Resonance Spectroscopy (13C NMR). The evaluated parameters fluctuated strongly
      during the first 3 weeks which was the most active period of the composting
      process. The principal components analysis (PCA) results showed that four classes
      of the samples were clearly distinguishable, in which the physiochemical
      parameters were similar, and that the dynamics of the composting process was
      significantly influenced by C/N and moisture content. The 13C NMR results
      indicated that O-alkyl-C was the predominant group both in the solid and water
      soluble fractions (WSF), and the decomposition of O-alkyl-C mainly occurred
      during the active stage. In general, the various parameters indicated that
      windrow composting is a feasible treatment that can be used for the resource
      reuse of agricultural wastes.

PMID- 29182982
TI  - Moderate intermittent negative pressure increases invasiveness of MDA-MB-231
      triple negative breast cancer cells.
AB  - BACKGROUND: To investigate the effect moderate intermittent negative pressure
      breast reconstructive model exerts on human triple negative breast cancer cell
      (TNBC) invasion and explore the related mechanism. METHODS: The human TNBC cell
      line MDA-MB-231 was used. Cells in external volume expansion (EVE) group were
      exposed to an intermittent -25 mmHg for 12 h; the pressure for non-EVE group was
      constantly 0 mmHg. In vivo, MDA-MB-231 cell suspensions were injected
      subcutaneously into dorsal skin of nude mice (n = 27 mice/group). Tumors on mice
      in EVE group received -25 mmHg suction 3 h/day; while mice in non-EVE group were
      under normal pressure. Cell invasion assay, ELISA, RT-PCR, western blot analysis
      and immunohistochemistry were used to evaluate the inflammation, epithelial
      mesenchymal transition (EMT) and angiogenesis between the two groups in both
      vitro and vivo experiments. RESULTS: MDA-MB-231 cells in the EVE group were more
      invasive and had higher expressions of IL-8 (30.02 +/- 10.44 pg/ml vs. 18.82 +/-
      9.26 pg/ml, P < 0.05) and TNF-alpha (20.59 +/- 4.72 pg/ml vs. 14.10 +/- 3.36
      pg/ml, P < 0.05) than the non-EVE group. Grafted MDA-MB-231 tumors in EVE group
      showed a more obvious epithelial-mesenchymal transition at 2 week and better
      angiogenesis at 2 and 4 week, respectively. CONCLUSION: Moderate intermittent
      negative pressure induces MDA-MB-231 cells to be more invasive. Future studies
      should figure out other effects this intervention may bring. Clinical studies
      should also be conducted to further evaluate its safety and optimize the clinical
      model.

PMID- 29182984
TI  - Bioaccessibilities and health implications of heavy metals in exposed-lawn soils
      from 28 urban parks in the megacity Guangzhou inferred from an in vitro
      physiologically-based extraction test.
AB  - This study focused on characterizing the oral bioaccessibilities and human health
      risks of eight heavy metals (Cd, Pb, Cr, Ni, Cu, Zn, Fe, and Mn) in surface
      exposed lawn soils from 28 urban parks in Guangzhou. The physiologically-based
      extraction test (PBET) method was used to assess bioavailability (in gastric and
      intestinal phases) and human health risk was assessed via statistical modelling
      (carcinogenic risk assessment, hazard quotients and hazard indices). Mean
      bioaccessibilities of Cd, Pb, Cr, Ni, Cu, Zn, Fe, and Mn from all soil samples
      were 50.90 +/- 17.67%, 5.81 +/- 1.67%, 7.12 +/- 3.24%, 17.91 +/- 18.34%, 11.93 +/
      2.88%, 34.33 +/- 10.02%, 1.68 +/- 0.48%, 26.71 +/- 5.06%, respectively. The
      concentrations of most heavy metals were higher in the gastric phase, except for
      Cr and Ni which remained higher in the intestinal phase. Principal component
      analysis revealed that the bioaccessibilities of the heavy metals could be split
      into three groupings, based on the urban park of soil origin. The carcinogenic
      risk probabilities for Pb and Cr were under the acceptable level (< 1 * 10-4) for
      both adults and children. The hazard quotient and hazard index values indicated
      no significant risk of non-carcinogenic effects to children or adults exposed to
      Guangzhou urban park soils. This research will help inform further risk
      assessment and management of heavy metal contaminants in urban environments.

PMID- 29182985
TI  - Assessment of metal pollution in the Lambro Creek (Italy).
AB  - This study assessed the effect of metal pollution in the Lambro Creek (Southern
      Italy). Water, sediment and biota were collected at six sampling sites (June) for
      metal concentration assessment (Cr, Cu, Ni, Pb and Zn). Sequential extraction was
      performed to determine the distribution of metals in different geochemical
      sediment fractions. The influence of pH and leaching time on the release of
      metals from sediment to the water column was investigated via remobilization
      tests. A battery of toxicity tests (Vibrio fischeri, Raphidocelis subcapitata,
      Phaeodactylum tricornutum, and Daphnia magna) with multi-endpoints
      (bioluminescence, growth inhibition, and immobilization) was used to determine
      the overall toxicity in sediment water extracts. The results showed that metals
      did not exceed the probable effect concentration levels, with Cr concentration
      exceeding the threshold effect concentration level at all sampling points except
      for the one closer to the source of the creek, suggesting potential negative
      effect on the biota. Considering the cumulative criterion unit, sediment
      contamination was moderate at all sampling sites, except for L3 and L5 where
      biota was exposed to a very high risk. With respect to sequential analysis, the
      most readily available fraction of metal can be generalised as Ni > Cr > Cu > Zn
      > Pb. For better understanding the fate of metals in the water-sediment
      environment, their biogeochemical cycles should also be investigated in small
      creeks including both fresh (watercourse) and saltwater (river mouth) sediments.

PMID- 29182983
TI  - Mammospheres of hormonal receptor positive breast cancer diverge to triple
      negative phenotype.
AB  - OBJECTIVES: This study aimed to characterize mammospheres from hormonal receptor
      (HR) positive and triple-negative breast cancer (TNBC), hypothesizing a
      differential profile of CSC and differentiation markers, and a stemness
      enrichment when successive sphere forming-protocols are performed. METHODS:
      Breast cancer cells MCF-7 and HCC1806 were submitted to sphere-forming protocols.
      The first sphere generation (MS1) was cultured in adherent conditions (G1). This
      procedure was repeated and generations of mammospheres (MS1, MS2, and MS3) and
      sphere-derived cells in adherent conditions (G1, G2, and G3) were obtained. The
      mammosphere forming capacity, self-renewal, area and doubling time were
      evaluated. Flow cytometry regarding CD133, CD24, and CD44 and western-blot
      regarding aldehyde dehydrogenase (ALDH), hormonal receptors and P53 expression
      was performed. RESULTS: Breast cancer cell lines harboured the capacity to form
      spheres, which originated derived adherent populations. The sphere-forming
      capacity was enhanced in HCC1806-MS3 compared to MS1. Self-renewal was higher in
      MCF-7 mammospheres, which also had an increased area. The putative CSC markers
      CD133 showed tendency to be enhanced in mammospheres but the CD44+/CD24-/low
      phenotype was not identified. The expression of ALDH was greater in mammospheres
      from MCF-7 and HCC1806 than in the respectively derived adherent cells. The
      expression of oestrogen receptor (ER)-alpha, progesterone receptor (PR) and P53
      decreased in MCF-7 spheres. ER-beta expression was lower in mammospheres from
      both cell lines compared with parental and derived adherent populations.
      CONCLUSIONS: Loss of HR and P53 expression in HR-positive mammospheres evidences
      the minor population of CSC which shares characteristics with the TNBC phenotype.

PMID- 29182986
TI  - Amelioration of cadmium-induced testes' damage in rats by the bone marrow
      mesenchymal stem cells.
AB  - Cadmium (Cd) and its compounds are highly toxic to virtually all organ systems of
      the mammals. Cd-induced testicular injuries have been reported in various animal
      species, using different protocols. The self-renewal capacity and the ability to
      generate different specialized cell types make the mesenchymal stem cells (MSCs)
      one of the ideal choices for restoring tissue damages of various etiologies. The
      use of bone marrow-derived MSCs (BM-MSCs) is among the most recent strategies to
      repair the Cd-induced testicular damage, but empirical studies in this regard are
      largely missing. Keeping in view the CD-induced testicular damage and the
      suggested restorative functions of BM-MSCs, the objectives of the current study
      were twofold: to induce testicular injury in Sprague-Dawley (SD) rats by a single
      intraperitoneal (i.p.) 2mg/kg Cd injection; and to study the reparative potential
      of BM-MSCs in Cd-induced testicular damage in adult male rats. The SD rats were
      randomly divided into three groups (n = 10 each): control (untreated), Cd-group
      (i.p. 2mg/kg Cd), and Cd+SC group (i.p. 2mg/kg Cd plus two intravenous doses of 1
      * 106 BM-MSCs via penile vein). After four weeks, Cd-group showed a significantly
      lower (p < 0.05) weight-gain, sperm count, and sperm viability, as well as led to
      testicular atrophy, necrosis, fibrosis, calcification, and marked perivascular
      lymphocytic infiltration, as compared to the untreated controls. As hypothesized,
      the rats exposed to Cd, but treated with BM-MSCs (Cd+SC group), showed a lesser
      degree of Cd-induced damage. In conclusion, the findings of current investigation
      indicate a reversal of Cd-induced testicular injury by BM-MSCs. The study
      supports the previously suggested notion that BM-MSCs can repair the Cd-induced
      testes' damage in rats.

PMID- 29182987
TI  - Lipoprotein(a) and abdominal aortic aneurysm risk: The Atherosclerosis Risk in
      Communities study.
AB  - BACKGROUND AND AIMS: No prospective study has investigated whether elevated
      lipoprotein(a) concentrations are associated with an increased risk of abdominal
      aortic aneurysm (AAA). We aimed to prospectively investigate this association.
      METHODS: In 1987-1989, the Atherosclerosis Risk in Communities study measured
      plasma lipoprotein(a) in 13,683 participants aged 45-64 years, without a history
      of AAA surgery. We followed them for incident, clinical AAA events through 2011.
      RESULTS: During the 272,914 person-years of follow-up, over a median of 22.6
      years, we documented 505 incident AAA events. The age-, sex-, and race-adjusted
      model showed that individuals in the highest quintile of plasma lipoprotein(a)
      had an increased risk of AAA. Further adjustment for the other potential
      confounding factors, including other plasma lipids (high- and low-density
      lipoprotein cholesterol and triglyceride concentrations), attenuated the
      association, but individuals in the highest versus lowest quintile of plasma
      lipoprotein(a) still had a significantly increased risk of AAA [hazard ratio (95%
      confidence interval): 1.57 (1.19-2.08)]. Interaction testing suggested no
      difference in the associations for whites and African Americans (p for
      interaction = 0.96). A restricted cubic spline analysis demonstrated a positive
      dose-response relation of plasma lipoprotein(a) with AAA, with a steep increase
      in AAA risk above the 75th percentile (p for overall association = 0.0086, p for
      non-linear association = 0.097). CONCLUSIONS: In this population-based cohort
      study, elevated lipoprotein(a) concentrations were independently associated with
      an increased risk of AAA. The association reflected a threshold of increased AAA
      risk at high lipoprotein(a) concentrations, rather than a steady monotonic
      association.

PMID- 29182988
TI  - Elevated circulating TGF-beta is not the cause of increased atherosclerosis
      development in biglycan deficient mice.
AB  - BACKGROUND AND AIMS: Vascular biglycan contributes to atherosclerosis development
      and increased biglycan expression correlates with increased atherosclerosis.
      However, mice deficient in biglycan have either no reduction in atherosclerosis
      or an unexpected increase in atherosclerosis. Biglycan deficient mice have
      systemically elevated TGF-beta, likely due to lack of sequestration of TGF-beta
      in the extracellular matrix. The purpose of this study was to determine if
      prevention of TGF-beta elevations in biglycan deficient mice affected
      atherosclerosis development. METHODS: Biglycan deficient mice were crossed to
      Ldlr deficient mice. Diabetes was induced via streptozotocin and all mice were
      fed a high cholesterol diet. Diabetic biglycan wild type and biglycan deficient
      Ldlr deficient mice were injected with the TGF-beta neutralizing antibody 1D11 or
      the irrelevant control antibody 13C4. RESULTS: Biglycan deficient mice had
      significantly elevated plasma TGF-beta levels, which was further increased by
      diabetes, and significantly increased atherosclerosis. There was a significant
      correlation between TGF-beta concentrations and atherosclerosis. However, despite
      nearly complete suppression of plasma TGF-beta levels in mice treated with the
      TGF-beta neutralizing antibody 1D11, there was no significant difference in
      atherosclerosis between mice with elevated TGF-beta levels and mice with
      suppressed TGF-beta levels. CONCLUSIONS: The increased atherosclerosis in
      biglycan deficient mice does not appear to be due to elevations in TGF-beta.

PMID- 29182989
TI  - Investigations for radiculopathy: The patient perspective. A qualitative,
      interpretative inquiry.
AB  - BACKGROUND: Clinical guidelines recommend that investigations, such as magnetic
      resonance imaging, are offered only when likely to change management. Meanwhile,
      the optimal process of diagnosing radiculopathy remains uncertain and, in
      clinical practice, differences of opinion can occur between patient and clinician
      regarding the perceived importance of investigations. OBJECTIVES: To explore
      peoples' experiences of investigations and the effect of concordance between
      clinical presentation and investigation findings. METHODS: In this qualitative
      study, 14 participants who had recently undergone investigations for a clinical
      presentation of radiculopathy were purposively recruited from an NHS, Primary
      Care Service in the United Kingdom. Based on the principles of interpretative
      phenomenological analysis, individual, semi-structured interviews were recorded
      and transcribed verbatim. Data were managed using a framework approach and
      analysed thematically. FINDINGS: Although people reported wanting investigations
      to understand the cause of symptoms and inform management, access to them was
      reported to be difficult and protracted. When investigations revealed potentially
      relevant findings, people experienced relief, validation, empowerment and
      decisive decision-making. Disappointment emerged, however, regarding treatment
      options and waiting times, and long-term prognosis. When investigations failed to
      identify relevant findings, people were unable to make sense of their symptoms,
      relinquish their search to identify the cause, or to move forward in their
      management. CONCLUSIONS: This study provides the first reported in-depth
      interpretation of peoples' experience of undergoing investigations specifically
      for radiculopathy. Important implications have been identified for: investigation
      referral criteria; shared-decision-making; information sharing and managing
      expectations and disappointment. CLINICALTRIALS. GOV REFERENCE: UOS-2307-CR.

PMID- 29182990
TI  - Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy:
      Comparison of RECIST 1.1, irRECIST and iRECIST criteria.
AB  - BACKGROUND: Immune checkpoint inhibitors are an important tool in the therapeutic
      strategy against metastatic non-small cell lung cancer (NSCLC); however,
      radiological evaluation is challenging due to the emergence of atypical patterns
      of responses. Several evaluation criteria have been proposed, such as the
      Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, immune 
      related RECIST (irRECIST) and iRECIST, but have not been systematically compared
      in a homogeneous population. PATIENTS AND METHODS: We conducted a monocentric
      retrospective analysis of consecutive advanced NSCLC patients treated with an
      anti-programmed cell death-1 or anti-program death-ligand 1. Response patterns
      and the discordance between RECIST 1.1, irRECIST and iRECIST guidelines were
      described, and associations of response patterns and clinical outcome were
      explored. RESULTS: Overall, 160 patients treated between February 2013 and
      October 2016 were included. Atypical responses were observed in 20 patients
      (13%), including eight pseudoprogressions (PsPDs) (5%) and 12 dissociated
      responses (8%). Thirteen of the 20 patients demonstrated clinical benefit. Per
      the RECIST 1.1, 37 patients (23%) showed an objective response or stable disease,
      and 123 patients (77%) exhibited progression. Eighty progressive patients were
      assessable for irRECIST and iRECIST: 15 patients were assessed differently;
      however, only three (3.8%) mismatches with a theoretical impact on the
      therapeutic decision were identified. Patients with PsPD or dissociated response
      had higher overall survival than patients with true progression. CONCLUSION:
      Atypical responses (PsPD/dissociated response) occurred in 13% of NSCLC patients
      under immune checkpoint inhibitors. Based on survival analyses, the RECIST 1.1
      evaluation underestimated the benefit of immune checkpoint inhibitors in 11% of
      the progressive patients. Immune-related RECIST and iRECIST identified these
      unconventional responses, with a 3.8% discrepancy rate.

PMID- 29182991
TI  - Influences of feedstock type and process variables on hydrochar properties.
AB  - In this study, the effect of process variables, such as temperature,
      biomass:water ratio and reaction time, in hydrothermal carbonization (HTC) has
      been studied for different type biomasses. Response surface methodology was used
      to study the influence of each factors as well as their combined interactive
      effect on the mass yield and energy density of hydrochars. The results showed
      that the temperature and time were significant factors effecting the mass yield
      and energy densification ratio in HTC of the sunflower stalk and algae, whereas
      temperature was only significant factor in HTC of poultry litter. The
      biomass:water ratio was found insignificant for all tested biomasses. In
      addition, the fuel properties of hydrochars were compared with the properties of
      biochar derived from torrefaction at 300  degrees C. The results showed that for
      all tested biomass, the biochars had lower volatile matter and fixed carbon than
      hydrochars.

PMID- 29182992
TI  - Process design and economics of a flexible ethanol-butanol plant annexed to a
      eucalyptus kraft pulp mill.
AB  - This work proposes a strategy, from a process design standpoint, for pulp
      companies to enter the Brazilian ethanol market. The flexible plant converts
      eucalyptus-derived glucose to either ethanol or butanol (according to market
      conditions) and xylose only to butanol production. Depending on the biomass
      pretreatment technology, Monte Carlo simulations showed that the Net Present
      Value (NPV) of the flexible plant increases by 20-28% in relation to an ethanol
      dedicated plant. Whereas the lower costs of the steam explosion technology turns
      the investment more attractive (NPV = 184 MMUSD; IRR = 29%), the organosolv
      technology provides better flexibility to the plant. This work also shows that
      excessive power consumption is a hurdle in the development of flash fermentation
      technology chosen for the flexible plant. These results indicate that
      conventional batch fermentation is preferable if the enzymatic hydrolysis step
      operates with solids loading up to 20 wt%.

PMID- 29182993
TI  - Lymphocyte count in peripheral blood is not associated with the level of clinical
      response to treatment with fingolimod.
AB  - BACKGROUND: Fingolimod is an efficient and safe drug for treating relapsing
      remitting multiple sclerosis (RRMS). In vivo, fingolimod is phosphorylated and
      binds to "sphingosine-1-phosphate"(S1P) receptors that are expressed in a wide
      range of cells, including lymphocytes. Under the effect of fingolimod,
      lymphocytes are retained in lymphoid tissues through the regulation of S1P1
      receptors. The aim of the present study was to assess whether the degree of
      lymphopenia was correlated to the positive treatment response of RRMS patients
      with fingolimod. METHODS: Data was sourced from the MSBase Registry. Patients
      were divided into two groups, according to the lymphocyte count on peripheral
      blood examination. Annualized Relapse Rate (ARR), time to first relapse and time
      to six-month confirmed disability progression were compared between groups.
      RESULTS: Group one consisted of 202 patients who reached 750 lymphocytes/mm3
      during treatment while the comparison group two included 101 patients who never
      reached less than 1000 lymphocytes/mm3 in peripheral blood during the observation
      period. There were no differences between groups in ARR, time to first relapse or
      time to six-month confirmed disability progression. CONCLUSION: The degree of
      lymphopenia in peripheral blood was not associated to the positive treatment
      response of fingolimod in RRMS patients.

PMID- 29182994
TI  - Motor fatigability in persons with multiple sclerosis: Relation between different
      upper limb muscles, and with fatigue and the perceived use of the arm in daily
      life.
AB  - BACKGROUND: Motor fatigability is increasingly acknowledged in persons with MS
      (pwMS). It is unknown whether fatigability is generalized across upper limb
      muscles and relates to fatigue and perceived difficulties in upper limb use.
      METHODS: This observational case-controlled study included twenty PwMS (median
      EDSS = 3, range 1.5-6.5) and twenty healthy controls who performed 30" sustained
      maximal muscle contractions for index finger abduction, hand grip, elbow flexion
      and shoulder abduction. A static fatigue index (SFI) was calculated to assess
      motor fatigability for each muscle group. PwMS completed the Fatigue Severity
      Scale (FSS) and Modified Fatigue Index Scale (MFIS), to quantify severity and
      perceived impact of fatigue and the Manual Ability Measure (MAM-36) reflecting
      perceived difficulty in using the upper limbs. Comparisons between groups and
      muscles was made by t-tests. Associations between outcomes were calculated with
      correlation coefficients. RESULTS: Fatigue was highest in pwMS. PwMS showed
      preserved muscle strength and a greater motor fatigability in elbow flexors
      compared to healthy controls. SFI of elbow flexors and shoulder abductors were
      associated, and contributed to FSS and MFIS. SFI of elbow flexors and finger
      abductors predicted half of the variation in MAM-36. CONCLUSION: Increased motor
      fatigability was only present in elbow flexors of PwMS, indicating that
      expression of motor fatigability is not generalized. Fatigability was associated
      with perceived fatigue (impact) and daily life upper limb use. Results are
      preliminary given the small sample size with predominantly persons with mild MS.

PMID- 29182995
TI  - Cocaine-induced multifocal leukoencephalopathy mimicking Balo's concentric
      sclerosis: A 2-year follow-up with serial imaging of a single patient.
AB  - Cocaine abuse may cause stroke, metabolic or multifocal inflammatory
      leukoencephalopathy. We described a patient with cocaine abuse who presented with
      Balo's type acute multifocal leukoencephalopathy. Magnetic Resonance Imaging
      (MRI) of the brain showed onion like patchy concentric ring enhancement on T1
      weighted MRI with gadolinium. Balo's Concentric Sclerosis like radiological
      findings related to cocaine has not been reported. Levamisole is now frequently
      used as an ingredient in cocaine and may cause leukoencephalopathy. It is
      recommended to check urine levamisole levels in patients with cocaine-induced
      leukoencephalopathy with or without mimicking Balo's Concentric Sclerosis. On the
      other hand, it is also possible that the cocaine use was coincidental and this
      was a demyelinating case arising de novo in patient who uses cocaine.

PMID- 29182996
TI  - Distinguishing among multiple sclerosis fallers, near-fallers and non-fallers.
AB  - BACKGROUND: Fall rates among adults with multiple sclerosis are consistently
      greater than 50%, but near-falls (i.e. a trip or stumble) are often undocumented.
      Furthermore, little is known about the circumstances surrounding fall and near
      fall events. The purpose of this study was to examine the similarities and
      differences among non-fallers, near-fallers and fallers with multiple sclerosis,
      including the circumstances that surround falls and near-falls. METHODS: In a
      single visit, 135 multiple sclerosis participants completed the Hopkins Falls
      Grading Scale, a custom questionnaire investigating circumstances surrounding
      falls and near-falls, and performed the Timed Up and Go and Timed 25-Foot Walk
      tests. Mann-Whitney tests were used to examine differences between fallers, near
      fallers and non-fallers. Multiple logistic regression with AIC criterion was used
      to examine associations of circumstances with the odds of falling vs. near
      falling. Cumulative odds ordinal logistic regression was used to analyze the
      association between each of the walking tests and the susceptibility of the
      individual for falls or near-falls. RESULTS: 30% of individuals reported falls,
      while 44% reported near-falls over a 1-year period. Non-fallers completed the
      walking tests more quickly than near-fallers (p < 0.0045), and fallers (p <
      0.0001); near-fallers and fallers demonstrated similar motor profiles.
      Individuals were more likely to sustain a fall rather than a near-fall under the
      following circumstances: transferring outside the home (p = 0.015) and tripping
      over an obstacle (p = 0.025). Performing 1-second slower on the walking tests
      increased the odds of a history of a fall by 6-20%. CONCLUSION: Near-falls occur
      commonly in individuals with MS; near-fallers and fallers reported similar
      circumstances surrounding fall events and demonstrated similar performance on
      standard timed walking tests. Clinicians monitoring individuals with MS should
      consider evaluation of the circumstances surrounding falls in combination with
      quantitative walking measures to improve determination of fall risk and
      appropriate rehabilitation interventions.

PMID- 29182997
TI  - Bioanalytical methods for the quantification of hydromorphone, fentanyl,
      norfentanyl, morphine, morphine-3beta-glucuronide and morphine-6beta-glucuronide
      in human plasma.
AB  - The aim of this study was to develop an assay for the quantification of
      hydromorphone, morphine, fentanyl and the metabolites norfentanyl, morphine-3beta
      glucuronide and morphine-6beta-glucuronide in human plasma to support
      pharmacokinetic studies investigating the large interpatient variability in
      response to opioid treatment. For the quantitation of hydromorphone, morphine,
      fentanyl and its metabolite norfentanyl aliquots of 200MUL human potassium EDTA
      plasma were deproteinized with deuterated internal standards in a mixture of
      acetonitrile and acetone, followed by a liquid-liquid extraction with 4% ammonium
      hydroxide and ethyl acetate. Morphine-3beta-glucuronide and morphine-6beta
      glucuronide were extracted by a solid phase extraction using 10mM ammonium
      carbonate pH 8.8 and a deuterated internal standards solution. Morphine,
      hydromorphone, fentanyl and norfentanyl were separated on an Aquity UPLC(r) BEH
      C18 column 1.7MUm, 100mm*2.1mm at 50 degrees C. Separation, was achieved on a
      gradient of methanol with an overall run time of 6min. The compounds were
      quantified by triple-quadrupole mass spectrometry in the positive ion
      electrospray ionization mode. Morphine-3beta-glucuronide and morphine-6beta
      glucuronide were separated on a VisionHT C18-P; 3MUm 2.1*50mm, column at 40
      degrees C on a gradient of acetonitrile, with an overall run time of 10min. Both
      methods were precise and accurate, with within-run and between-run precisions
      within acceptable limits and accuracy ranging from 84.0 to 105.5%. The methods
      were successfully applied to support clinical pharmacological studies in patients
      treated with opioids for the treatment of moderate to severe cancer-related pain.

PMID- 29182998
TI  - Three newly identified lipophilic flavonoids in Tanacetum parthenium
      supercritical fluid extract penetrating the Blood-Brain Barrier.
AB  - Feverfew (Tanacetum parthenium L.) as a perennial herb has been known for
      centuries due to its medicinal properties. The main sesquiterpene lactone,
      parthenolide is considered to be responsible for the migraine prophylactic
      effect, however the pharmacological benefits of the lipophilic flavonoid
      components can not be neglected. Supercritical fluid extraction (7% ethanol,
      22MPa, 64 degrees C) was carried out on the leaves of Tanacetum parthenium L.
      from which the presence of methylated flavonoids beside parthenolide and other
      sesquiterpene lactones were indicated by preliminary LC-MS analyses. Specific
      Parallel Artificial Membrane Permeability Assay (PAMPA) was applied to identify
      the components capable to cross the Blood-Brain Barrier (BBB). Three lipophilic
      flavonoids were detected on the acceptor side, that were isolated (Prep-HPLC) and
      identified as sudachitin, aceronin and nevadensin (LC-MS/MS, NMR). These
      flavonoids were also characterized individually by PAMPA-BBB model. The presence
      of sudachitin and nevadensin was proven in the Asteraceae family, but neither of
      the three flavonoids were reported in Tanacetum parthenium L.

PMID- 29182999
TI  - Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics
      studies of cannabidiolic acid (CBDA).
AB  - Hemp seed oil from Cannabis sativa L. is a very rich natural source of important
      nutrients, not only polyunsaturated fatty acids and proteins, but also terpenes
      and cannabinoids, which contribute to the overall beneficial effects of the oil.
      Hence, it is important to have an analytical method for the determination of
      these components in commercial samples. At the same time, it is also important to
      assess the safety of the product in terms of amount of any psychoactive
      cannabinoid present therein. This work presents the development and validation of
      a highly sensitive, selective and rapid HPLC-UV method for the qualitative and
      quantitative determination of the main cannabinoids, namely cannabidiolic acid
      (CBDA), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD),
      tetrahydrocannabinol (THC), cannabinol (CBN), cannabigerol (CBG) and
      cannabidivarin (CBDV), present in 13 commercial hemp seed oils. Moreover, since
      decomposition of cannabinoid acids generally occurs with light, air and heat,
      decarboxylation studies of the most abundant acid (CBDA) were carried out in both
      open and closed reactor and the kinetics parameters were evaluated at different
      temperatures in order to evaluate the stability of hemp seed oil in different
      storage conditions.

PMID- 29183001
TI  - Tailoring the appearance: what will synthetic cells look like?
AB  - Recently, the bottom-up assembly of a synthetic cell has emerged as a daring
      novel approach that can be expected to have major impact in generating
      fundamental insight in the organization and function of actual biological cells,
      as well as in stimulating a broad range of applications from drug delivery
      systems to chemical nanofactories. A crucial feature of any such synthetic cell
      is the architectural scaffold that defines its identity, compartmentalizes its
      inner content, and serves as a protective and selective barrier against its
      environment. Here we review a variety of potential scaffolds for building a
      synthetic cell. We categorize them as membranous structures (liposomes, fatty
      acid vesicles, polymersomes), emulsions (droplets and colloidosomes), and
      membrane-less coacervates. We discuss recent advances for each of them, and
      explore their salient features as candidates for designing synthetic cells.

PMID- 29183002
TI  - An MR/MRI compatible core holder with the RF probe immersed in the confining
      fluid.
AB  - An open frame RF probe for high pressure and high temperature MR/MRI measurements
      was designed, fabricated, and tested. The open frame RF probe was installed
      inside an MR/MRI compatible metallic core holder, withstanding a maximum pressure
      and temperature of 5000 psi and 80  degrees C. The open frame RF probe was
      tunable for both 1H and 19F resonance frequencies with a 0.2 T static magnetic
      field. The open frame structure was based on simple pillars of PEEK polymer upon
      which the RF probe was wound. The RF probe was immersed in the high pressure
      confining fluid during operation. The open frame structure simplified fabrication
      of the RF probe and significantly reduced the amount of polymeric materials in
      the core holder. This minimized the MR background signal detected. Phase encoding
      MRI methods were employed to map the spin density of a sulfur hexafluoride gas
      saturating a Berea core plug in the core holder. The SF6 was imaged as a high
      pressure gas and as a supercritical fluid.

PMID- 29183003
TI  - Direct hyperpolarization of micro- and nanodiamonds for bioimaging applications -
      Considerations on particle size, functionalization and polarization loss.
AB  - Due to the inherently long relaxation time of 13C spins in diamond, the nuclear
      polarization enhancement obtained with dynamic nuclear polarization can be
      preserved for a time on the order of about one hour, opening up an opportunity to
      use diamonds as a new class of long-lived contrast agents. The present
      communication explores the feasibility of using 13C spins in directly
      hyperpolarized diamonds for MR imaging including considerations for potential in
      vivo applications.

PMID- 29183000
TI  - The lymphatics in infiltrating ductal carcinoma (IDC) of the breast.

PMID- 29183004
TI  - Adaptive suppression of power line interference in ultra-low field magnetic
      resonance imaging in an unshielded environment.
AB  - Power-line harmonic interference and fixed-frequency noise peaks may cause stripe
      artifacts in ultra-low field (ULF) magnetic resonance imaging (MRI) in an
      unshielded environment and in a conductively shielded room. In this paper we
      describe an adaptive suppression method to eliminate these artifacts in MRI
      images. This technique utilizes spatial correlation of the interference from
      different positions, and is realized by subtracting the outputs of the reference
      channel(s) from those of the signal channel(s) using wavelet analysis and the
      least squares method. The adaptive suppression method is first implemented to
      remove the image artifacts in simulation. We then experimentally demonstrate the
      feasibility of this technique by adding three orthogonal superconducting quantum
      interference device (SQUID) magnetometers as reference channels to compensate the
      output of one 2nd-order gradiometer. The experimental results show great
      improvement in the imaging quality in both 1D and 2D MRI images at two common
      imaging frequencies, 1.3 kHz and 4.8 kHz. At both frequencies, the effective
      compensation bandwidth is as high as 2 kHz. Furthermore, we examine the
      longitudinal relaxation times of the same sample before and after compensation,
      and show that the MRI properties of the sample did not change after applying
      adaptive suppression. This technique can effectively increase the imaging
      bandwidth and be applied to ULF MRI detected by either SQUIDs or Faraday coil in
      both an unshielded environment and a conductively shielded room.

PMID- 29183005
TI  - Microarray Expression Profile of Circular RNAs in Plasma from Primary Biliary
      Cholangitis Patients.
AB  - BACKGROUND/AIMS: Circular RNAs (circRNAs) play a crucial role in the occurrence
      of several diseases, including autoimmune diseases. However, their role in
      primary biliary cholangitis (PBC) remains unclear. Here, we aimed to determine
      the circRNA expression profile in plasma from PBC patients and further explore
      the value of circRNA in diagnosing PBC. METHODS: CircRNA microarrays were used to
      determine circRNA expression profiles in plasma samples from 6 PBC patients and 6
      healthy controls. Statistical analyses identified differentially expressed
      circRNAs, and these circRNAs were verified by qRT-PCR in 29 PBC patients and 30
      healthy controls. MicroRNA (miRNA) target prediction software identified putative
      miRNA response elements (MREs), which were used to construct a map of circRNA
      miRNA interactions for the differentially expressed circRNAs. RESULTS: Our
      results indicated that there were 18 up-regulated and 4 down-regulated circular
      RNAs in the plasma from PBC patients compared with that from healthy individuals.
      Among the differentially expressed circRNAs, hsa_circ_402458 (P=0.0033),
      hsa_circ_087631 and hsa_circ_406329 (P=0.0185) were up-regulated, and
      hsa_circ_407176 (P=0.0066) and hsa_circ_082319 were down-regulated in the PBC
      group versus the healthy group as demonstrated by qRT-PCR. In particular,
      hsa_circ_402458 was significantly higher in PBC patients not receiving UDCA
      treatment than in PBC patients receiving UDCA treatment (P=0.0338). The area
      under the receiver operating characteristic curve for hsa_circ_402458 for
      diagnosing PBC was 0.710 (P=0.005). For hsa_circ_402458, two putative miRNA
      targets, hsa-miR-522-3p and hsa-miR-943, were predicted. CONCLUSIONS: circRNA
      dysregulation may play a role in PBC pathogenesis, and hsa_circ_402458 shows
      promise as a candidate biomarker for PBC.

PMID- 29183006
TI  - Health-Related Quality of Life in 536 Long-Term Prostate Cancer Survivors after
      Treatment with Leuprorelin Acetate: A Combined Retrospective and Prospective
      Analysis.
AB  - INTRODUCTION: We investigated the health-related quality of life (HRQoL) of long
      term prostate cancer patients who received leuprorelin acetate in microcapsules
      (LAM) for androgen-deprivation therapy (ADT). METHODS: The observational study
      was carried out by 30 office-based German urologists in 536 prostate cancer (PCa)
      patients treated for >=5 years with LAM and in 116 patients of an age-matched
      control group (CG). Data on HRQoL and health status was collected prospectively
      using validated questionnaires QLQ-C30, QLQ-PR25 and Karnofsky Index. Data on
      effectiveness (clinical response, prostate specific antigen [PSA], testosterone)
      and safety was collected retrospectively from patients' health records. We used
      descriptive statistics to analyze the data. RESULTS: The mean treatment duration
      was 8.6 years (range 4.5-19.8 years). General health status (QLQ-C30) was
      comparable for both groups. Differences were observed regarding physical - and
      role functioning. ADT patients rated single items slightly worse than CG.
      Karnofsky-Index showed comparable high values (median of 90%). QLQ-PR25 revealed
      more PCa-related symptoms for ADT patients. Within 6 months, median PSA level
      declined >90% and median testosterone levels declined below castration level from
      4.0 to 0.2 ng/mL. Clinical response (European Organisation for Research and
      Treatment of Cancer criteria) was observed in at least 90% of ADT patients.
      CONCLUSIONS: Long-term ADT with LAM is a well-accepted, tolerated, effective, and
      low-burden treatment option for patients with advanced, hormone-sensitive PCa.

PMID- 29183007
TI  - MiR-193a-3p is an Important Tumour Suppressor in Lung Cancer and Directly Targets
      KRAS.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) have emerged as major regulators of tumour
      development and progression in non-small cell lung cancer (NSCLC). However, the
      role of miR-193a-3p in NSCLC is still unclear. METHODS: Quantitative RT-PCR was
      used to detect miR-193a-3p expression levels in NSCLC tumour tissues. CCK8, EdU
      and cell migration assays were performed to analyse the biological functions of
      miR-193a-3p in NSCLC cells. Luciferase reporter assays were used to validate the
      bioinformatics-predicted target genes of miR-193a-3p. Western blotting and
      RNA/DNA interference carried out to evaluate the association between miR-193a-3p
      and KRAS. RESULTS: miR-193a-3p expression was decreased in the NSCLC tumour
      tissues. We investigated the biological effects of miR-193a-3p both in vivo and
      in vitro and found that enforced expression of miR-193a-3p inhibited tumour
      formation and suppressed cell proliferation and cell migration. KRAS was found to
      be a potential target of miR-193a-3p, and dual luciferase reporter assays showed
      that miR-193a-3p directly binds to the 3'-untranslated region (3'-UTR) of KRAS
      mRNA. In addition, we found that changing the expression of KRAS had the opposite
      results to those induced by miR-193a-3p in the NSCLC cells. Importantly,
      simultaneous overexpression of miR-193a-3p and KRAS could counteract the effects
      of both on cellular functions. CONCLUSION: These findings highlight an important
      role for miR-193a-3p as a tumour suppressor in NSCLC pathogenesis via the
      regulation of KRAS expression.

PMID- 29183008
TI  - Correlates of Pulmonary Function in Children with Sickle Cell Disease and
      Elevated Fetal Hemoglobin.
AB  - OBJECTIVE: The current study was carried out to compare pulmonary function tests
      (PFTs) in pediatric Kuwaiti sickle cell disease (SCD) patients to age-matched
      normal controls and to investigate the association of PFTs with selected clinical
      and laboratory parameters. Subjects andMethods: There were 38 patients with SCD
      and 36 controls in the study. The patients were recruited from the Pediatric
      Hematology Clinics of Mubarak Al-Kabeer and Al-Amiri Hospitals, Kuwait, and were
      studied in steady state. The controls were healthy, non-sickle cell siblings of
      the patients. Forced expiratory volume in 1 s (FEV1), forced vital capacity
      (FVC), total lung capacity, and other PFT parameters were obtained using a
      constant-volume, variable-pressure, body plethysmograph. Hemoglobin, fetal
      hemoglobin, serum bilirubin, and lactate dehydrogenase were determined using
      standard methods. RESULTS: The mean ages of the patients and controls were 10.5
      +/- 3.2 and 10.5 +/- 3.5 years, respectively. The FEV1% predicted of 84.1 +/-
      15.4% among the patients was significantly lower than the 92.1 +/- 11.8% in the
      controls (p = 0.003). The FVC% predicted was also significantly lower (p = 0.022)
      in the patients than in the controls, although the values were generally within
      the normal range. There was no association of FEV1 with pain phenotype, acute
      chest syndrome (ACS), or blood transfusions. Also, there was no significant
      correlation with reticulocytes, bilirubin, or lactate dehydrogenase. CONCLUSIONS:
      In this study, changes in PFT, especially FEV1, developed early in the SCD
      patients. There was no demonstrable association with frequent vaso-occlusive
      crisis, ACS, and other variables. Hence, there is a need for follow-up studies
      with serial PFTs to identify vulnerable patients, who might need intervention to
      prevent early mortality.

PMID- 29183009
TI  - Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect
      on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation
      Potential and Enhanced Antioxidant Ability.
AB  - BACKGROUND/AIMS: Radiation therapy is an important treatment for thoracic cancer;
      however, side effects accompanied with radiotherapy lead to limited tumor control
      and a decline in patient quality of life. Among these side effects, radiation
      induced lung injury (RILI) is the most serious and common. Hence, an effective
      remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult
      stem cells that have been demonstrated to be an effective treatment in some
      disease caused by tissue damage. However, unlike other injuries, RILI received
      limited therapeutic effects from implanted MSCs due to local hypoxia and
      extensive reactive oxygen species (ROS) in irradiated lungs. Since the poor
      survival of MSCs is primarily due to hypoxia and ROS generation, we hypothesize
      that persistent and adaptive hypoxia treatment induces enhanced resistance to
      hypoxic stress in implanted MSC. The aim of this study is to investigate whether
      persistent and adaptive hypoxia treatment of bmMSCs prior to their
      transplantation in injured mice enhanced survival and improved curative effects
      in RILI. METHODS: Primary bmMSCs were obtained from the marrow of six-week-old
      male C57BL6/J mice and were cultured either under normoxic conditions (21% O2) or
      hypoxic conditions (2.5% O2). Mice were injected with normoxia/hypoxia MSCs after
      thoracic irradiation (20 Gy). The therapeutic effects of MSCs on RILI were
      assessed by pathological examinations that included H&E staining, Masson staining
      and alpha-SMA staining; meanwhile, inflammatory factors were measured using an
      ELISA. The morphology of MSCs in vitro was recorded using a microscope and
      identified by flow cytometry, cell viability was measured using the CCK-8 assay,
      the potential for proliferation was detected by the EdU assay, and ROS levels
      were measured using a ROS fluorogenic probe. In addition, HIF-1alpha and several
      survival pathway proteins (Akt, p-Akt, Caspase-3) were also detected by western
      blotting. RESULTS: Implanted MSCs alleviated both early radiation-induced
      pneumonia and late pulmonary fibrosis. However, hypoxia MSCs displayed a more
      pronounced therapeutic effect compared to normoxia MSCs. Compared to normoxia
      MSCs, the hypoxia MSCs demonstrated greater cell viability, an enhanced
      proliferation potential, decreased ROS levels and increased resistance to hypoxia
      and ROS stress. In addition, hypoxia MSCs achieved higher activation levels of
      HIF-1alpha and Akt, and HIF-1alpha played a critical role in the development of
      resistance. CONCLUSION: Hypoxia enhances the therapeutic effect of mesenchymal
      stromal cells on radiation-induced lung injury by promoting MSC proliferation and
      improving their antioxidant ability, mediated by HIF-1alpha.

PMID- 29183010
TI  - Mild-to-Moderate Chronic Kidney Disease and Geriatric Outcomes: Analysis of Cross
      Sectional Data from the Berlin Aging Study II.
AB  - BACKGROUND: Mild-to-moderate chronic kidney disease (CKD G3a) is prevalent in
      older adults. Substantial evidence suggests that individuals with advanced CKD
      face a high risk for common geriatric conditions, like functional impairment and
      cognitive decline, whereas the relationships between mild-to-moderate CKD and
      functional impairment and cognitive decline, but also poor nutritional status and
      mood disorders, are still unclear. OBJECTIVE: The aim of this study was to
      explore associations between mild-to-moderate CKD and impairments in the core
      domains of geriatric assessment (GA) in a large cohort of community-dwelling
      older adults. METHODS: This was a cross-sectional analysis of 1,476 participants
      of the Berlin Aging Study II. Study participants were stratified as to presence
      or absence of CKD G3a (estimated glomerular filtration rate [eGFR] 45-59
      mL/min/1.73 m2 vs. eGFR >=60 mL/min/1.73 m2). GA comprised the following
      instruments: the Activities of Daily Living Scale (ADL), the Timed up and Go
      (TUG), the Tinetti test (Tinetti), the Mini-Mental-State Examination (MMSE), the
      Geriatric Depression Scale (GDS), and the Mini Nutritional Assessment (MNA). We
      used logistic regression models to estimate multivariable-adjusted associations
      between CKD G3a and impairments in the respective domains. RESULTS: A total of
      282 subjects with mild-to-moderate CKD (CKD G3a) were identified (19.1%).
      Overall, the prevalence of impairments identified was higher among subjects with
      compared to without CKD G3a (21 vs. 15.9%, p = 0.043). In multivariable-adjusted
      models, CKD G3a was consistently associated with increased odds of an impaired
      gait performance as to the TUG (adjusted odds ratio 2.06, 95% CI 1.04-4.09). In
      contrast, on average, individuals with and without CKD G3a did not differ as to
      their results in the MMSE, the ADL, the MNA, and the GDS. CONCLUSION: GA
      identified impairments in 21 versus 15.9% of older adults with and without mild
      to-moderate CKD, respectively. However, except for an increased likelihood of
      impaired gait performance (TUG) with mild-to-moderate CKD, we did not find
      independent associations between mild-to-moderate CKD and geriatric conditions.

PMID- 29183011
TI  - Transoral Robotic Surgery with Sialendoscopy for a Plunging Ranula.
AB  - BACKGROUND/AIMS: Plunging ranulas are oral mucoceles that often cannot be
      visualized directly and thus can be challenging to diagnose and differentiate
      from other neck lesions. Surgery is the preferred treatment option, but the
      optimal approach requires careful consideration. METHODS: We report the case of a
      plunging ranula presenting as an isolated neck mass in a 33-year-old patient.
      This patient was treated with a novel transoral robotic surgery (TORS)-assisted
      approach aided by sialendoscopy. RESULTS: TORS allowed for exceptional
      visualization and access to the plunging ranula and sublingual gland while
      avoiding critical neurovascular structures. The patient healed well without
      recurrence or complications. CONCLUSION: The TORS approach with sialendoscopy for
      plunging ranulas described in this case report shows promise and should be
      considered for certain clinical presentations. Additional studies evaluating the
      effectiveness of TORS for plunging ranulas may be indicated.

PMID- 29183012
TI  - Differential Expression of the Aryl Hydrocarbon Receptor and Transforming Growth
      Factor Beta 1 in Chronic Rhinosinusitis with Nasal Polyps with Allergic Rhinitis.
AB  - OBJECTIVE: This study aimed to determine the aryl hydrocarbon receptor (AhR) and
      transforming growth factor beta 1 (TGF-beta1) expression levels in chronic
      rhinosinusitis (CRS) and their possible correlation with allergic state and
      tissue remodeling. METHODS: Patients were enrolled and divided into the following
      groups: CRS without nasal polyps (NP) without allergic rhinitis (AR) (CRSsNPsAR;
      n = 20), CRS with NP with AR (CRSwNPwAR; n = 20), CRS with NP without AR
      (CRSwNPsAR; n = 20), and controls (n = 15). Tissue samples were analyzed by
      Masson trichrome staining for collagen, while the location and expression of AhR
      and TGF-beta1 were analyzed by immunohistochemistry, quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), and Western blotting. RESULTS:
      The collagen amounts as well as AhR and TGF-beta1 mRNA and protein expression
      levels were significantly increased in the CRSsNPsAR group compared with the
      CRSwNP (CRSwNPsAR and CRSwNPwAR) samples (p < 0.01). However, higher collagen
      amounts (p < 0.05) and higher TGF-beta1 (p < 0.05) but lower AhR expression
      levels (p < 0.05) were detected in the CRSwNPwAR versus the CRSwNPsAR patients.
      Both AhR and TGF-beta1 expression were positively correlated with the collagen
      level in CRS samples (p < 0.01). CONCLUSIONS: Elevated AhR expression may be
      involved in the progression of tissue remodeling in CRSsNPsAR similar to TGF
      beta1 expression. Conversely, lower AhR expression may be involved in allergic
      reactions in CRSwNPwAR.

PMID- 29183013
TI  - Uremic Pruritus: An Itch with Ominous Consequences.

PMID- 29183014
TI  - Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and
      Schwann Cells Progenitors Migration.
AB  - BACKGROUND/AIMS: Migration of Schwann cells (SCs) progenitors and neurite
      outgrowth from embryonic dorsal root ganglions (DRGs) are two central events
      during the development of the peripheral nervous system (PNS). How these two
      enthralling events preceding myelination are promoted is of great relevance from
      basic research and clinical aspects alike. Recent evidence demonstrates that
      biophysical cues (extracellular matrix stiffness) and biochemical signaling act
      in concert to regulate PNS myelination. Microenvironment stiffness of SCs
      progenitors and embryonic neurites dynamically changes during development.
      METHODS: DRG explants were isolated from day 12.5 to 13.5 mice embryos and plated
      on laminin-coated substrates with varied stiffness values. After 4 days in
      culture and immunostaining with specific markers, neurite outgrowth pattern, SCs
      progenitors migration, and growth cone shape and advance were analyzed with
      confocal fluorescence microscopy. RESULTS: We found out that growing substrate
      stiffness promotes directional neurite outgrowth, SCs progenitors migration,
      growth cone advance and presumably axons fasciculation. CONCLUSIONS: DRG explants
      are in vitro models for the research of PNS development, myelination and
      regeneration. Consequently, we conclude the following: Our observations point out
      the importance of mechanosensitivity for the PNS. At the same time, they prompt
      the investigation of the important yet unclear links between PNS biomechanics and
      inherited neuropathies with myelination disorders such as Charcot-Marie-Tooth 1A
      and hereditary neuropathy with liability to pressure palsies. Finally, they
      encourage the consideration of mechanosensitivity in bioengineering of scaffolds
      to aid nerve regeneration after injury.

PMID- 29183016
TI  - Meetings and Conferences.

PMID- 29183015
TI  - Oncological Rehabilitation and Cancer Survivorship.

PMID- 29183019
TI  - Society Bulletins.

PMID- 29183018
TI  - Cytogenetic Characterization of a Population of Acanthodactylus lineomaculatus
      Dumeril and Bibron, 1839 (Reptilia, Lacertidae), from Southwestern Morocco and
      Insights into Sex Chromosome Evolution.
AB  - Acanthodactylus lineomaculatus is now regarded as an ecotype of A. erythrurus
      with which it has been recently synonymized. Despite the wide range of A.
      erythrurus, karyological data for this species are scarce and limited to
      classical cytogenetic studies carried out in individuals from only 2 locations
      (central Spain and Spanish enclave of Melilla on the northwestern Mediterranean
      Moroccan coast). Here, for the first time, we cytogenetically characterized
      individuals of A. lineomaculatus from the southwestern Moroccan Atlantic coast
      with the aim to increase the karyological knowledge of this wide-ranging species
      and to assess if any chromosomal changes can be found in this ecotype in
      comparison to other populations of this species. The diploid number of the
      individuals investigated is 2n = 38 which is typical of most lacertids. Active
      NORs were located telomerically in a medium-small pair of chromosomes, and no
      inactive NORs were detected. C-banding revealed an intensely heterochromatic W
      chromosome composed of AT-rich (centromere and long arm telomeric region) and GC
      rich (most of the long arm) regions, with extended interstitial telomeric
      sequences. These telomere-like repeats occupy the GC-rich heterochromatin of the
      W. The DNA composition of the W represents a trait distinguishing A.
      lineomaculatus (southwestern Morocco) from A. erythrurus from Spain that possess
      a DAPI-positive (AT-rich) W chromosome. In conclusion, these results add further
      evidence to the remarkable karyotype conservation in lacertid lizards, although
      differences in NOR location and in W chromosome structure among populations could
      suggest an incipient speciation mediated by chromosome changes in this wide
      ranging lizard species.

PMID- 29183020
TI  - Clinical Application of Quantitative Foetal Fibronectin for the Prediction of
      Preterm Birth in Symptomatic Women.
AB  - AIM: To evaluate the clinical application of the new Hologic quantitative foetal
      fibronectin (qfFN) bedside test for the prediction of spontaneous preterm birth
      (sPTB) in patients with symptoms suggestive of spontaneous threatened preterm
      labour (sPTL). METHODS: A prospective observational study with 154 pregnant women
      presenting signs and symptoms of sPTL was conducted. These women were subjected
      to a qfFN test between 22 and 35 weeks of gestation For each cut-off threshold,
      the ability to predict sPTB at within 14 days of conducting the test and <37
      weeks was assessed by calculating the positive predictive value (PPV), negative
      predictive value (NPV), likelihood ratios, odds ratios, sensitivity, and
      specificity. RESULTS: For the outcome of delivery within 14 days of the test,
      qfFN <10 ng/mL had a 100% NPV and >200 ng/mL produced a 50.0% PPV; thus, qfFN
      added enhanced discrimination between high- and low-risk patients. The overall
      rate of sPTB (<37) was 13.3% (16/120), which increased progressively with
      increasing levels of fFN, with rates of 9.8% (8/81), 11.5% (3/26), 14.2% (1/7),
      50% (3/6) within the 4 categories (fFN 0-9, 10-49, 50-200, 200+) respectively.
      CONCLUSIONS: The use of the qfFN testing in symptomatic patients allowed for more
      accurate identification of women at risk of sPTB and thus more directed
      management.

PMID- 29183021
TI  - Digital Applications in Cytopathology: Problems, Rationalizations, and
      Alternative Approaches.
AB  - OBJECTIVE: The aim of this work was to raise awareness of problems using digital
      applications for examining, teaching, and applying telecytology at King Abdulaziz
      Medical City (KAMC), Riyadh, Saudi Arabia; University of Nebraska Medical Center
      (UNMC), Omaha, NE, USA; and University of Pittsburgh Medical Center (UPMC),
      Pittsburgh, PA, USA. The objective was to rationalize problems and propose
      alternative digital approaches. STUDY DESIGN: We sought to identify solutions to
      improve the following: (a) interpretive examination scores at KAMC for complex
      cytological templates (i.e., high-grade squamous intraepithelial lesions [HSIL])
      when using static digital images (SDI) of cells in regions of interest (ROI); (b)
      visualization of cells in 3D clusters when teaching at UNMC using 2D and 3D whole
      slide imaging (WSI); and (c) visualization of cells through streaming
      telecytology at UPMC. RESULTS: Composite SDI (CSDI) improved test scores for
      complex interpretations (i.e., HSIL) by converging diagnostic criteria from
      multiple ROI. Multiplane focusing through z-stacked WSI facilitated the teaching
      of cytological entities characterized by 3D cell clusters and consultative
      telecytology through robotic cell analysis. CONCLUSIONS: Adequately visualized
      cytomorphology and multiplane focusing are essential for virtual cytopathology
      examinations, teaching, or consultative telecytology. Visualization of diagnostic
      criteria through 2D or 3D imaging is critical. Panoptiq panoramic WSI with
      integrated z-stacked video clips enables optimal applied telecytology.

PMID- 29183022
TI  - Rehabilitation of Cancer Survivors with Long-Term Toxicities.
AB  - The prognosis of cancer patients is constantly improving, which increases the
      importance of securing long-term quality of life. While therapy of treatment
      related disability mostly succeeds a cancer-specific treatment, physicians'
      awareness of simultaneous supportive therapy is rising. Early interventions such
      as physical exercise during chemotherapy are effective in reducing conditions
      such as fatigue. Specific sensorimotor training is able to improve or even
      prevent impairment of balance caused by neurotoxic agents. Although targeted
      therapies reduce the risk of side effects, combinations with established drugs
      have to be monitored with regard to cardiotoxicity, which is already a concern in
      children's cancer therapy and is now also focused on in long-term adult
      survivors. Improvement in diagnosis und surgical procedures have reduced
      impairments such as lymphedema. Furthermore, management and quality of life of
      breast cancer patients benefit from evidence showing that physical exercise and
      resistance training do not increase the risk of developing lymphedema.

PMID- 29183024
TI  - Should All Extremely Premature Infants Be Screened for Pulmonary Hypertension?

PMID- 29183023
TI  - The Recovery of Microvascular Status Evaluated by Optical Coherence Tomography
      Angiography in Patients after Successful Macular Hole Surgery.
AB  - PURPOSE: The aim of this study was to evaluate the optical coherence tomography
      angiography (OCTA) features of patients who underwent successful macular hole
      (MH) surgery. METHODS: Nineteen patients who underwent surgery in a single eye
      due to MH and 13 healthy subjects as a control group were included in the study.
      Vascular densities, flow indexes, and the foveal avascular zone (FAZ) area in
      superficial and deep retinal capillary plexuses were evaluated by OCTA in the
      right eyes of the control group, and both the surgical and healthy fellow eyes of
      the patients. RESULTS: The mean vascular densities of the superficial and deep
      capillary plexuses were significantly lower in the surgical eyes than in the
      control group (44.1 vs. 49.6%, p = 0.002, and 47.3 vs. 59.1%, p = 0.009,
      respectively). The mean superficial and deep capillary flow indexes were
      significantly lower in the surgical eyes than in the control group (0.85 vs.
      1.35, p = 0.003, and 0.57 vs. 1.45, p = 0.001, respectively), while the mean
      superficial and deep FAZ area were significantly greater in the surgical eyes in
      comparison to the control group (0.55 vs. 0.32, p < 0.001, and 0.64 vs. 0.37, p =
      0.001, respectively). There was no difference between the flow indexes of both
      layers of the healthy fellow eyes and the control group. CONCLUSIONS: These
      preliminary results may be an explanation for unsatisfactory visual gain after
      surgery, despite the successful anatomical closure of the MH.

PMID- 29183025
TI  - Can Early Dissection of Cervical Lymph Nodes Improve Prognosis in Squamous Cell
      Carcinomas of the Hard Palate.
AB  - Squamous cell carcinomas of the hard palate and maxillary alveolar ridge are rare
      tumours with a poor prognosis. Lymph node dissection is recommended for tumours
      with nodal involvement, and is rarely performed in the absence of adenopathy. We
      report a series of patients with squamous cell carcinomas and evaluate the rate
      of lymph node invasion and its impact on survival. This is a retrospective study
      of 72 patients treated for squamous cell carcinoma of the hard palate and
      maxillary alveolar ridge between January 1, 1998 and December 31, 2008 in two
      cancer centres. Using clinical and radiological assessment, tumours were
      classified as T1-T2 in 25 patients (34.7%) and T3-T4 in 47 patients (65.3%). At
      diagnosis, 16 (22.2%) patients had clinical and/or radiological nodal involvement
      and 7 patients (9.7%) distal metastasis. Among N0 patients, 13 (18%) experienced
      isolated lymph node recurrence. Two-year global survival was 60%; 5-year survival
      was 34%. The rate of lymph node invasion observed in squamous cell carcinoma of
      the hard palate and maxillary alveolar ridge does not differ from other oral
      cavity sites. Because nodal recurrence worsens the prognosis of such a patient,
      lymph node dissection should be considered at an early stage, even among N0
      patients.

PMID- 29183026
TI  - Late Effects and Long-Term Follow-Up after Cancer in Childhood.
AB  - Today, 80% of children and adolescents with cancer survive their disease. From
      the results of aftercare research arises the question: Are the survivors also
      healthy? Many late effects depend on the type of cancer and its treatment.
      Patients with brain tumors and with malignant sarcomas are very often affected by
      secondary diseases. Data from the USA report that around 2/3 of all patients
      still living 30 years after their cancer treatment in childhood suffer from late
      complications. Equivalent figures for Germany were previously unavailable. In
      accordance with the guidelines, regular follow-ups to diagnose a relapse or
      possible late effects have mostly been carried out in the primary children's
      hospitals. In adolescence and in young adulthood, this regimen does no longer
      serve the patients' mental and physical needs. To ensure appropriate care for
      this maturing patient group, interdisciplinary approaches (e.g., aftercare
      consultations) are required in which pediatric oncologists collaborate with
      colleagues from the field of internal medicine and other disciplines. Individual,
      risk-adapted (depending on the cancer treatment) aftercare plans based on pre
      existing aftercare recommendations must be drawn up for every patient and to
      secure the early diagnosis of possible late effects. The conservation of health
      and quality of life after cancer treatment (in all age groups) will in the future
      not only represent a social but also an economic consideration.

PMID- 29183027
TI  - Identification of Subpathway Signatures For Ovarian Cancer Prognosis by
      Integrated Analyses of High-Throughput miRNA and mRNA Expression.
AB  - BACKGROUND/AIMS: Ovarian cancer (OC) causes more death and serious conditions
      than any other female reproductive cancers, and many expression signatures have
      been identified for OC prognoses. However, no significant overlap is found among
      signatures from different studies, indicating the necessity of signature
      identifications at the functional level. METHODS: We performed an integrated
      analyses of miRNA and gene expressions to identify OC prognostic subpathways
      (pathway regions). Using The Cancer Genome Atlas data set, we identified core
      prognostic subpathways, and calculated subpathway risk scores using both miRNA
      and gene components. Finally, we performed global risk impact analyses to
      optimize core subpathways using the random walk algorithm. RESULTS: Subpathway
      level analyses displayed more robust results than the gene- and miRNA-level
      analyses. Moreover, we verified the advantage of core subpathways over the entire
      pathway-based results and their prognostic performance in two independent
      validation data sets. Based on the global impact score, 13 subpathway signatures
      were selected and a combined subpathway-based risk score was further calculated
      for OC patient prognoses. CONCLUSIONS: Overall, it was possible to systematically
      perform integrated analyses of the expression levels of miRNAs and genes to
      identify prognostic subpathways and infer subpathway risk scores for use in OC
      clinical applications.

PMID- 29183028
TI  - Radiofrequency Ablation of Atrial Fibrillation in Patients with Ebstein's
      Anomaly: A Two-Case Report.
AB  - Ebstein's anomaly (EA) is a rare congenital heart disease characterized by
      "atrialization" of the right ventricle, due to apical displacement of the
      tricuspid leaflets into the right ventricle. Patients with EA may develop all
      kinds of supraventricular arrhythmias requiring radiofrequency ablation. Atrial
      fibrillation (Afib) is a common arrhythmia in EA patients, and results in
      debilitating symptoms that often require surgical treatment. This is a follow-up
      report of 2 patients with EA undergoing radiofrequency ablation for Afib. The
      first patient underwent pulmonary vein isolation (PVI) and the ablation of a
      concomitant atrioventricular nodal reentrant tachycardia. The second patient was
      also treated with a PVI and a redo PVI 8 months later. Both patients remain in
      sinus rhythm 8 months on. Radiofrequency ablation is the therapy of choice for
      patients with pharmacological refractory Afib, but it is not common in patients
      with EA.

PMID- 29183029
TI  - Successful Evidence-Based Treatment of Patients with Advanced Pancreatic Cancer
      in Community-Based Oncology Group Practices.
AB  - BACKGROUND: Randomized clinical trials do not reflect the day-to-day reality of
      patient care; hence, the treatment of patients with advanced pancreatic cancer in
      oncology group practices was evaluated. PATIENTS AND METHODS: All consecutive
      patients with advanced pancreatic cancer who were treated between 01/2012 and
      12/2015 in 4 oncology group practices were analyzed retrospectively using SPSS
      software. RESULTS: 324 patients with a median age of 70 years (range 32-94 years)
      were analyzed. The majority were male (56%) and had distant metastases (74%).
      Chemotherapy was the major modality of treatment (86%) with a median overall
      survival (OS) of 33.3 weeks (range 1.7-245.4 weeks). Chemotherapy significantly
      (p < 0.001) improved OS in comparison to best supportive care only (37.6 vs. 13.9
      weeks). Patients with locally advanced disease had a better prognosis compared to
      patients with metastases (median OS 49.6 vs. 30.4 weeks; p < 0.001). An age
      adjusted Charlson comorbidity score of >= 9 was found to influence the OS
      significantly (p = 0.004). CONCLUSION: Chemotherapy remains the main modality of
      treatment for patients with advanced pancreatic cancer with an OS comparable to
      prospective randomized trials. The OS of this patient cohort has remained the
      same over the last 20 years despite advances in treatment modalities.

PMID- 29183030
TI  - Emodin Inhibits ATP-Induced Proliferation and Migration by Suppressing P2Y
      Receptors in Human Lung Adenocarcinoma Cells.
AB  - BACKGROUND/AIMS: Extracellular ATP performs multiple important functions via
      activation of P2 receptors on the cell surface. P2Y receptors play critical roles
      in ATP evoked response in human lung adenocarcinoma cells (A549 cells). Emodin is
      an anthraquinone derivative originally isolated from Chinese rhubarb, possesses
      anticancer properties. In this study we examined the inhibiting effects of emodin
      on proliferation, migration and epithelial-mesenchymal transition (EMT) by
      suppressing P2Y receptors-dependent Ca2+ increase and nuclear factor-kappaB (NF
      KB) signaling in A549 cells. METHODS: A549 cells were pretreated with emodin
      before stimulation with ATP for the indicated time. Then, intracellular Ca2+
      concentration ([Ca2+]i) was measured by Fluo-8/AM staining. Cell proliferation
      and cell cycle progression were tested by CCK8 assay and flow cytometry In
      addition, wound healing and western blot were performed to determine cell
      migration and related protein levels (Bcl-2, Bax, claudin-1, NF-kappaB). RESULTS:
      Emodin blunted ATP/UTP-induced increase of [Ca2+]i and cell proliferation
      concentration-dependently Meanwhile, it decreased ATP-induced cells accumulation
      in the S phase. Furthermore, emodin altered protein abundance of Bcl-2, Bax and
      claudin-1 and attenuated EMT caused by ATP. Such ATP-induced cellular reactions
      were also inhibited by a nonselective P2Y receptors antagonist, suramin, in a
      similar way to emodin. Besides, emodin could inhibit activation of NF-kappaB,
      thus suppressed ATP-induced proliferation, migration and EMT. CONCLUSION: Our
      results demonstrated that emodin inhibits ATP-induced proliferation, migration,
      EMT by suppressing P2Y receptors-mediated [Ca2+]i increase and NF-kappaB
      signaling in A549 cells.

PMID- 29183031
TI  - Novel PCR Assays for the Detection of Biological Agents Responsible for Wheat
      Rust Diseases: Puccinia triticina and Puccinia striiformis f. sp. tritici.
AB  - The species Puccinia triticina (Pt) and Puccinia striiformis f. sp. tritici (Pst)
      are devastating cereal pathogens that cause leaf and stripe rust diseases. We
      developed PCR assays for the species-specific detection of Pt and Pst, 2
      biological agents that cause wheat rust disease. For each pathogen, we validated
      3 primer sets that target the second largest subunits of the RNA polymerase II
      (rpb2) and beta-tubulin 1 (tub1) genes. The specificities of the primers were
      verified using naturally infected plant materials with visual symptoms of
      disease. All primer sets amplified a single DNA fragment of the expected length.
      The primer sets LidPr15/16, LidPr1/2, and LidPs13/14 were able to detect small
      amounts of pure fungal DNA with sensitivities of 0.1, 1, and 10 pg/MUL,
      respectively. A sufficient detection limit (1 pg/MUL to 5 ng/MUL) was observed
      for all assays when the sensitivity test was performed with host plant DNA. The
      study also evaluated the simultaneous detection of both rust pathogens, and the
      multiplex PCR assay generated amplicons of 240 and 144 bp in length for Pts
      (LidPs9/10) and Pt (LidPr1/2), respectively.

PMID- 29183032
TI  - Return to Work of Cancer Survivors.
AB  - Due to improving treatment options, the number of so-called long-term cancer
      survivors is steadily increasing. Current studies assume that more than 60% of
      adults survive their cancer. These patients have a variety of problems
      (chemotherapy-induced neuropathy, fatigue, etc.) that require very special care.
      In addition to somatic and psychological side effects of the cancer or its
      treatment, these patients also suffer from the financial and social consequences
      of the disease. Thus, for a long-term survivor of working age, the question of a
      'return to work' represents a significant problem since otherwise the financial
      existence of the patient, and often the family, may substantially deteriorate.
      Studies show that cancer patients classify financial worries with regard to the
      quality of life as more significant than physical or psychological side effects
      of the cancer or its treatment. Furthermore, there are initial studies showing
      that the social descent due to the disease may also prove relevant for cancer
      prognosis. In contrast, it was shown in studies and in a Cochrane analysis that
      professional assistance and support services are suitable for keeping patients in
      their professional lives. Therefore, both patients and physicians need to be
      aware of this problem.

PMID- 29183033
TI  - The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue
      Subscale): Validity and Reliability of the Iranian Version.
AB  - BACKGROUND: The aim of this study was to translate and validate the Functional
      Assessment of Chronic illnesses Therapy-Fatigue (FACIT-fatigue subscale) in Iran.
      METHODS: The Persian version of the FACIT-fatigue scale was developed using the
      forward-backward translation method. The questionnaire was then presented to a
      consecutive sample of breast cancer patients (n = 208) attending the Iranian
      Center of Breast Cancer (ICBC). The reliability was assessed by internal
      consistency and test-retest using Cronbach's alpha and intraclass correlation
      coefficient (ICC), respectively. Convergent validity was examined by correlation
      between the FACIT-fatigue scale and the Hospital and Depression Scale (HADS). In
      addition, discriminant validity was evaluated by the ability of the scale to
      differentiate between patients who differed in disease stage. RESULTS: The
      internal consistency of the questionnaire was excellent (Cronbach's alpha =
      0.92). The ICC for the FACIT-fatigue was 0.84. Strong correlations were observed
      between FACIT-fatigue and depression (r = -0.69) and anxiety (r = -0.72) scores.
      The FACIT-fatigue discriminated well between subgroups of patients who differed
      in stage (p < 0.001) and probable caseness of anxiety and depression disease (p <
      0.001). CONCLUSION: The Iranian version of the FACIT-fatigue subscale is a valid
      and reliable instrument to measure fatigue in cancer patients.

PMID- 29183034
TI  - Adjuvant Radiotherapy in High-Risk Squamous Cell Carcinoma of the Vulva: A Two
      Institutional Italian Experience.
AB  - BACKGROUND: The aim of this study was to assess the treatment benefit and
      patterns of recurrence for patients with high-risk vulvar squamous cell carcinoma
      treated with surgery followed by adjuvant radiotherapy (RT). PATIENTS AND
      METHODS: From January 1999 to June 2016, 51 patients underwent total or partial
      deep vulvectomy with inguinofemoral lymphadenectomy followed by adjuvant RT with
      45-50 Gy in 25 fractions +/- a 4-10 Gy boost. 17 (33.3%) women received
      concomitant chemotherapy. RESULTS: Median overall survival was 81 months. The 5
      year disease-free survival and overall survival rates were 52 and 63%,
      respectively. In univariate and multivariate analysis, patients aged <= 76 years
      and those receiving an RT total dose of > 54 Gy had a significantly lower risk of
      progression (p = 0.044 and 0.045; p = 0.012 and 0.018, respectively) and death (p
      = 0.015 and 0.011; p = 0.015 and 0.026, respectively). There was a trend towards
      a lower risk of progression for patients with tumor size <= 4 (p = 0.098) and
      negative lymphovascular space involvement (p = 0.080). Also, there was a trend
      towards a higher risk of death (p = 0.075) for grade 3 tumors. Concomitant
      chemotherapy provided no significant benefit. CONCLUSION: Only age and RT total
      dose are significant prognostic variables for squamous cell carcinoma of the
      vulva treated with primary surgery and adjuvant RT to improve local and
      locoregional control.

PMID- 29183035
TI  - User-Oriented Evaluation of a Robotic Rollator That Provides Navigation
      Assistance in Frail Older Adults with and without Cognitive Impairment.
AB  - BACKGROUND: Navigational skills decline with age, and this decline is even more
      pronounced in cognitively impaired (CI) older adults. Navigation assistance is an
      emerging functionality of robotic rollators (RRs). The evidence on the
      effectiveness of RR-integrated navigation systems in potential end-users is,
      however, scarce. OBJECTIVE: To determine whether RR-provided navigation
      assistance improves navigation within a real-life environment in the intended
      user group of frail older adults with and without cognitive impairment currently
      using a rollator in daily life. METHODS: A randomized, between-subject, 2 * 2
      factorial design was conducted to test the effects of navigation assistance and
      cognitive status on participants' navigation performance. Twenty CI (Mini-Mental
      State Examination [MMSE] 17-26) and 22 not cognitively impaired (NCI; MMSE >26)
      older rollator users (age 82.5 +/- 8.7 years) were included. Participants were
      matched for cognitive status (CI vs. NCI) and randomized to one of two
      conditions: RR (1) with or (2) without activated navigation system. All
      participants had to complete a two-section navigation path with the RR in an
      unfamiliar, real-life environment. Participants with RR-assisted navigation were
      supported in wayfinding by directional audio cues of the RR-integrated navigation
      system. Participants without RR-assisted navigation had to complete the sections
      by orienting themselves along conventional signposts. Outcomes were success rate,
      completion and stopping time, number of stops, walking distance, and gait speed.
      RESULTS: The navigation assistance condition had no significant effect on the
      success rate in the CI, NCI, or total group. We found significant interactions
      between navigation assistance and cognitive status for both sections (p = 0.002
      0.040), such that RR-assisted navigation reduced the completion time (both
      sections), stopping time (section 1), and number of stops (section 2) in the CI
      (p <= 0.001-0.014) but not in the NCI group. On the more complex section 2, RR
      assisted navigation led to a reduced stopping time and walking distance in the
      total group (p = 0.014-0.016). CONCLUSION: The RR-integrated navigation system
      was effective for improving navigation within a real-life environment in
      potential end-users, especially in those with cognitive impairment. This is the
      first study to provide statistical evidence on the effectiveness of an RR
      integrated navigation system in the intended user group.

PMID- 29183037
TI  - Efficacy of a New Post-Mouthwash Intervention (Wiping Plus Oral Nutritional
      Supplements) for Preventing Aspiration Pneumonia in Elderly People: A
      Multicenter, Randomized, Comparative Trial.
AB  - BACKGROUND/AIMS: Aspiration pneumonia is a common cause of death among the
      elderly (>=90-year-old) in nursing homes. Studies suggest that its incidence
      could be reduced by oral care interventions. We aimed to evaluate the efficacy of
      a new oral care intervention: wiping plus oral nutritional supplements (ONS).
      METHODS: This prospective observational study was conducted in 252 patients (age
      88.0 +/- 6.5 years) in 75 nursing homes, rehabilitation hospitals, and other care
      facilities. Patients were randomly divided into an intervention group (n = 74)
      and a control group (n = 107), whose members received conventional oral care.
      Body mass index, activities of daily living (Barthel index), and complete blood
      count and biochemistry parameters were measured at 2, 4, 6, and 8 months.
      RESULTS: The cumulative incidence of pneumonia at 8 months tended to be lower in
      the intervention than in the control group (7.8 vs. 17.7%, p = 0.056) and was
      significantly lower for men in the intervention group (p = 0.046). CONCLUSIONS:
      Our new intervention "wiping plus providing ONS" method appears to help prevent
      aspiration pneumonia, thereby reducing mortality risk. In this study, we
      disseminate information on how this method is used in Japan.

PMID- 29183036
TI  - Surgical Approach to "Right Hepatic Core": Deepest Region Surrounded by Major
      Portal Pedicles and Right Hepatic Vein.
AB  - BACKGROUND/AIMS: The resection of hepatic tumors located in the region surrounded
      by the right hepatic vein (RHV) and the portal pedicles of the right
      paramedian/lateral sector (the right hepatic core) remains a challenge for liver
      surgeons. The aim of this study was to demonstrate the surgical techniques and
      outcomes of our atypical-parenchyma-sparing hepatectomy (atypical-PSH) approach
      for the removal of tumors in the right hepatic core. METHODS: Perioperative
      records of 1,179 consecutive patients who had undergone hepatectomy for
      hepatocellular carcinoma or colorectal liver metastases from January 2006 to
      December 2014 were retrospectively reviewed. RESULTS: Twenty-six patients (2%)
      had a tumor in the right hepatic core. Among them, 20 patients underwent atypical
      PSH, including the anterior approach (resection of the right paramedian hepatic
      parenchyma, n = 9), posterior approach (resection of the right lateral hepatic
      parenchyma, n = 10), and transhepatic approach (tumor enucleation from the raw
      surfaces along the RHV, n = 1). Their postoperative outcomes were similar to the
      remaining 6 patients who had undergone right hepatectomy. CONCLUSIONS: Atypical
      PSH can be safely applied for the removal of tumors in the right hepatic core.
      This technique may have potential advantages in preserving hepatic function for
      postoperative chemotherapy and repeated hepatectomy for future recurrence.

PMID- 29183039
TI  - MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the
      Articular Chondrocytes.
AB  - BACKGROUND/AIMS: Osteoarthritis (OA) as a degenerative disease is a major problem
      in ageing populations. To better understand the molecular mechanisms in the
      pathogenesis of OA, this study explored the role of microRNA (miR)-146a in the
      articular chondrocytes. METHODS: The articular chondrocyte line ATDC5 was used to
      simulate inflammatory injury by LPS administration in vitro. Cell viability,
      apoptosis, mRNA expressions and productions of inflammatory factors were
      assessed, respectively. Mir-146a and Cxcr4 mRNA expressions were measured by qRT
      PCR. Targeting effect of miR-146a on Cxcr4 3'UTR was assessed by luciferase
      activity analysis. Protein expression levels of CXCR4 and main factors in
      PI3K/AKT, Wnt/beta-catenin signal pathways were measured by western blotting.
      RESULTS: LPS exposure suppressed cell viability, prompted apoptosis of ATDC5
      cells, and stimulated expression and release of inflammatory factors. MiR-146a
      was upregulated in LPS-induced cells. Overexpression of miR-146a further
      aggravated LPS-induced inflammatory injury, while it was reduced after miR-146a
      was knocked down. CXCR4 expression was negatively regulated by miR-146a. CXCR4
      was a direct target of miR-146a and thus involved in regulatory effect of miR
      146a on the injured chondrocytes, which was also related with phosphorylation
      levels of PI3K/AKT and expressions of Wnt/beta-catenin signal factors.
      CONCLUSION: miR-146a promoted inflammatory response of articular chondrocytes via
      targeting CXCR4 and suppressing CXCR4 expression. Overexpression of CXCR4 could
      attenuate the inflammatory injury. Our findings provided novel evidence which
      might be useful for further studies exploring therapeutic approaches for OA via
      targeting miR-146a.

PMID- 29183040
TI  - Oncological Rehabilitation.
AB  - An increasing number of patients are living with or surviving cancer due to
      improvements in detection and treatment. However, patients who survive cancer may
      experience functional disabilities that impact on health, quality of life and
      ability to work. For example, physical disorders may include fatigue, reduced
      muscle strength, cognitive dysfunction, paresthesia or nutrition problems, while
      mental symptoms may include anxiety, depression, fear of relapse or insomnia.
      Multidimensional oncological rehabilitation programs have been developed to
      address these disabilities and to help cancer patients and long-term survivors to
      reduce morbidity and to improve quality of life. There has been evidence showing
      that multidisciplinary oncological rehabilitation interventions involving
      physical, psycho-educational and vocational components led to a better quality of
      life and a higher rate of return to work than just usual care. In Germany,
      oncological rehabilitation is an integral part of the healthcare system and part
      of a modern cancer treatment that immediately follows operation, medical
      treatment or radiotherapy. Furthermore, it can be used if functional disabilities
      still remain years after cancer treatment. This review describes the German
      history and legal basis of oncological rehabilitation as well as the contents of
      and the evidence for this comprehensive and interdisciplinary treatment.

PMID- 29183041
TI  - Association Between Hyperreflective Dots on Spectral-Domain Optical Coherence
      Tomography in Macular Edema and Response to Treatment.
AB  - Purpose: To investigate the association between hyperreflective dots (HRDs) on
      spectral-domain optical coherence tomography (SD-OCT) and response to
      intravitreal bevacizumab (IVB) or dexamethasone injection in eyes with diabetic
      macular edema (DME) or macular edema due to retinal vein occlusion (RVO).
      Methods: A retrospective review was conducted involving patients with DME or
      macular edema due to RVO. Patients with treatment-naive macular edema were
      initially treated with three consecutive IVB injections and classified based on
      the treatment response to bevacizumab. After three consecutive IVB injections,
      bevacizumab nonresponders were treated using dexamethasone implants and
      reclassified based on the treatment response. The best-corrected visual acuity,
      number of HRDs, and outer plexiform layer (OPL) disruptions were analyzed
      according to the treatment response. Results: Eighty-two eyes with DME and 68
      eyes with RVO were included in this study. Thirty-six (43.9%) eyes with DME and
      22 (32.4%) eyes with RVO were bevacizumab nonresponders. The number of baseline
      HRDs in bevacizumab nonresponders (16.06 +/- 6.60 in DME, 14.23 +/- 4.09 in RVO)
      was significantly greater than that in responders (11.26 +/- 3.64, P < 0.001 in
      DME, 11.17 +/- 4.83, P = 0.013 in RVO), and it did not decrease after IVB
      injections. Unlike the response to bevacizumab, eyes that responded to
      dexamethasone implant but not to IVB had significantly more HRDs (19.56 +/- 6.75)
      than eyes that did not respond (11.50 +/- 3.78, P = 0.006). The OPL disruption
      rate was significantly higher in bevacizumab nonresponders than in responders (P
      < 0.001 in DME and P = 0.001 in RVO). Conclusions: In patients with DME or
      macular edema due to RVO, the number of HRDs on SD-OCT may be a predictive
      indicator of the response to IVB injection or dexamethasone implant. In
      bevacizumab responders, the number of HRDs on SD-OCT was small. In contrast, more
      HRDs, which might reflect increased inflammation in the retina, were observed in
      dexamethasone responders. Therefore, dexamethasone implants might be more
      effective in DME or RVO eyes with multiple HRDs and OPL disruption on SD-OCT.

PMID- 29183042
TI  - Expression and Regulation of S100 Fused-Type Protein Hornerin at the Ocular
      Surface and Lacrimal Apparatus.
AB  - Purpose: The S100 fused-type proteins hornerin (HRNR) and filaggrin-2 (FLG2) are
      members of the epidermal differentiation complex, which is involved in terminal
      differentiation of keratinocytes via cornification as well as maintenance of the
      epidermal antimicrobial barrier. We investigated the expression and possible
      regulation of HRNR and FLG2 at the ocular surface and in the lacrimal apparatus.
      Methods: Tissues of the lacrimal apparatus and ocular surface were analyzed
      systematically by means of RT-PCR, immunohistochemistry, and immuntransmission
      electron microscopy (iTEM) for their ability to express and produce HRNR and
      FLG2. In addition, inducibility and regulation of HRNR were studied in cultivated
      human corneal (HCE), conjunctival (HCjE), as well as meibomian gland (HMGEC)
      epithelial cell line by real-time RT-PCR. Results: RT-PCR, immunohistochemistry,
      and iTEM revealed constitutive expression of HRNR in the epithelium of cornea,
      conjunctiva, nasolacrimal ducts, and acinus cells of lacrimal and meibomian
      glands. HRNR also was detected in tears of healthy volunteers. No expression of
      FLG2 could be detected in tissue samples of the ocular surface and lacrimal
      apparatus. Real-time RT-PCR revealed a decreased HRNR gene expression after
      challenge with proinflammatory cytokines and supernatants of Escherichia coli and
      Pseudomonas aeroginosa in HCE cells, whereas HCjE cells revealed no changes. In
      HMGECs serum-induced differentiation and application of all-trans retinoic acid
      significantly increased HRNR gene expression. Conclusions: The data suggest that
      HRNR, but not FLG2, is a component of the ocular surface and lacrimal apparatus,
      including meibomian glands. HRNR seems to contribute to the maintenance of the
      epithelial barrier at the ocular surface and, thus, also may be involved in
      ocular surface diseases.

PMID- 29183043
TI  - Benzo(e)pyrene Inhibits Endothelium-Dependent NO-Mediated Dilation of Retinal
      Arterioles via Superoxide Production and Endoplasmic Reticulum Stress.
AB  - Purpose: To investigate whether benzo(e)pyrene (B(e)P), a toxicant in cigarette
      smoke, affects the endothelium-dependent nitric oxide (NO)-induced vasodilation
      of the retinal arterioles, and whether oxidative stress, distinct protein kinase
      signaling pathways, and endoplasmic reticulum (ER) stress are associated with the
      B(e)P-induced effect on the retinal arterioles. Methods: In this in vitro study,
      porcine retinal arterioles were isolated, cannulated, and pressurized without
      flow. These vessels were treated with intraluminal administration of B(e)P or
      B(e)P plus blockers for 180 minutes. Diametric changes to agonists were recorded
      by videomicroscopy. Results: Intraluminal treatment with 100 MUM B(e)P for 180
      minutes significantly reduced the arteriolar vasodilation caused by the
      endothelium-dependent NO-mediated agonists bradykinin and A23187 but not that
      caused by endothelium-independent NO donor sodium nitroprusside. The adverse
      effects of B(e)P on the vasodilatory action of bradykinin were prevented by the
      superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the
      nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) inhibitor
      apocynin, the c-Jun N-terminal kinase (JNK) inhibitor SP600125, the p38 mitogen
      activated protein kinase inhibitor SB203580, genistein, resveratrol (RSV), and
      the ER stress inhibitor 4-phenylbutyrate (4-PBA). The xanthine oxidase inhibitor
      allopurinol did not alter the effect of B(e)P on the vasodilatory action induced
      by bradykinin. Conclusions: B(e)P decreases the endothelium-dependent NO-induced
      vasodilation in the retinal arterioles through the production of superoxide from
      NADPH oxidase, which is linked to JNK and p38 kinase. The results suggested that
      ER stress is instrumental in B(e)P-induced endothelial dysfunction and that
      genistein and RSV might preserve endothelial function.

PMID- 29183044
TI  - Inflammatory and Neuronal Biomarkers Associated With Retinal Thinning in
      Pediatric HIV.
AB  - Purpose: The pathophysiology of neuroretinal thinning in children with human
      immunodeficiency virus (HIV) is poorly understood. The current study aimed to
      assess whether neuroretinal thinning in clinically stable perinatally HIV
      infected children was associated with biomarkers of immune activation,
      inflammation, and neuronal damage. Methods: Inflammation-associated and neuronal
      damage markers were measured in blood and cerebrospinal fluid (CSF) of HIV
      infected children aged 8 to 18 years. Using mixed-effects regression analyses, we
      assessed associations between these biomarkers and neuroretinal layer thickness,
      as measured with spectral-domain optical coherence tomography. Results: Thirty
      two HIV-infected children (median age 13.6 years, 50% male) were included. Blood
      plasma levels of interleukin-6, monocyte chemoattractant protein-1, and soluble
      intercellular adhesion molecule-1 were inversely correlated with foveal inner
      plexiform layer thickness (coef = -4.40, P < 0.001; coef = -9.67, P = 0.047; coef
      = -10.48, P = 0.042, respectively). Plasma interleukin-6 was inversely correlated
      with foveal ganglion cell layer thickness (coef = -2.49, P = 0.010). Total Tau
      levels in CSF were inversely correlated with outer nuclear layer and inner
      segments thickness (foveal: coef = -19.3, P = 0.029; pericentral: coef = -18.09,
      P = 0.006) and pericentral total retinal thickness (coef = -28.2, P = 0.017).
      Conclusions: Neuroretinal thinning was associated with inflammation-associated
      and neuronal injury biomarkers in a cohort of antiretroviral therapy-treated
      perinatally HIV-infected children. These findings suggest that ongoing immune
      activation, inflammation, and neuronal injury occur in parallel with retinal
      thinning in pediatric HIV.

PMID- 29183045
TI  - Peripapillary Microvascular Improvement and Lamina Cribrosa Depth Reduction After
      Trabeculectomy in Primary Open-Angle Glaucoma.
AB  - Purpose: To evaluate peripapillary microvascular changes in patients with primary
      open-angle glaucoma (POAG) after trabeculectomy using optical coherence
      tomography (OCT) angiography, and to determine the influence of lamina cribrosa
      (LC) displacement on changes in peripapillary microvasculature. Methods: The
      peripapillary retinal microvasculature and LC were imaged using OCT angiography
      and OCT-enhanced depth imaging, respectively. The microvasculature and LC depth
      (LCD) were measured before, and 1 week, 1 month, and 3 months after
      trabeculectomy. The microvascular improvement was arbitrarily defined as a
      reduction >30% of the area of vascular dropout (blue/black areas with <20% vessel
      density on the color-coded vessel density map). LCD was determined as the mean of
      vertical distance between the anterior LC surface and a reference plane of
      Bruch's membrane. Results: Thirty-one eyes of 31 POAG patients were included. At
      3 months postoperatively, intraocular pressure (IOP) and LCD were significantly
      decreased from 26.3 +/- 11.8 mm Hg to 12.5 +/- 3.6 mm Hg, and 501.1 +/- 130.2 MUm
      to 455.8 +/- 112.7 MUm, respectively (all P < 0.001), compared with baseline. The
      microvascular improvement was observed in 19 eyes (61.3%) at 3 months after
      trabeculectomy. The maximal reductions in IOP and LCD were significantly greater
      in eyes with improved microvasculature compared to eyes without improvement (P =
      0.020 and P = 0.005). The microvascular improvement was significantly associated
      with maximal reduction in LCD (odds ratio, 1.062; P = 0.026). Conclusions:
      Trabeculectomy can improve peripapillary retinal microcirculation in patients
      with POAG. This finding suggests that the reduction of LCD induced by lowering
      IOP may affect peripapillary microvascular improvement in eyes with POAG.

PMID- 29183046
TI  - In Vivo Analysis of Angle Dysgenesis in Primary Congenital, Juvenile, and Adult
      Onset Open Angle Glaucoma.
AB  - Purpose: The purpose of this study was to comparatively evaluate angle dysgenesis
      in vivo, among congenital, juvenile, and adult-onset open angle glaucoma
      patients. Methods: A cross-sectional evaluation of 96 glaucoma patients, 22
      children with primary congenital glaucoma (PCG) old enough to cooperate for
      optical coherence tomography (OCT), 34 juvenile-onset open angle glaucoma (JOAG)
      patients, 40 adult-onset primary open angle glaucoma (POAG), and 30 healthy
      subjects, was carried out using high-resolution anterior segment spectral domain
      (SD)-OCT. Subgroup analysis was done for presence/ absence of angle dysgenesis as
      defined by presence of abnormal tissue/hyperreflective membrane within angle
      recess and/or absence of Schlemm's canal (SC). Results: Morphologic features
      suggestive of angle dysgenesis such as the presence of abnormal tissue at the
      angle and a hyperreflective membranous structure covering the meshwork were seen
      in all PCG eyes (100%), in 14 (40%) JOAG eyes, and none of the POAG eyes in
      comparison to healthy eyes (P = 0.01, P = 0.03, and P = 0.23 for PCG, JOAG, and
      POAG, respectively). SC could be seen in 27 (90%) healthy eyes compared with only
      7 (30%) in PCG (P = 0.01) 20 (60%) JOAG eyes (P = 0.03), and 26 (65%) adult-onset
      POAG eyes (P = 0.23; chi2 test). Conclusions: Angle dysgenesis in the form of
      abnormal tissue at the angle/hyperreflective membrane and/or absence of SC could
      be identified on anterior segment SD-OCT, which can be used for in vivo
      evaluation of eyes with developmental glaucoma.

PMID- 29183047
TI  - Incorrect Data in Text.

PMID- 29183048
TI  - Data Errors in the Text and Tables.

PMID- 29183049
TI  - Data Errors in Table 2.

PMID- 29183050
TI  - The Public Health Consequences of Performance-Enhancing Substances: Who Bears
      Responsibility?

PMID- 29183051
TI  - Timing of Operations and Outcomes for Patients With Hip Fracture-It's Probably
      Not Worth the Wait.

PMID- 29183052
TI  - Capsules for Fecal Microbiota Transplantation in Recurrent Clostridium difficile
      Infection: The New Way Forward or a Tough Pill to Swallow?

PMID- 29183054
TI  - Map of DNA Sites Governing Gene Expression Finalized.

PMID- 29183053
TI  - Diagnostic Testing for Obstructive Sleep Apnea in Adults.

PMID- 29183055
TI  - Veterans Affairs Creates New Family Support Group.

PMID- 29183056
TI  - NIH Partners With Drug Makers to Advance Cancer Immunotherapy.

PMID- 29183058
TI  - Diagnostic Problems: Guest Editorial.

PMID- 29183059
TI  - Physicians and Advanced Practitioners Specializing in Nursing Home Care, 2012
      2015.

PMID- 29183060
TI  - Outcomes of Positive Airway Pressure for Sleep Apnea.

PMID- 29183061
TI  - Outcomes of Positive Airway Pressure for Sleep Apnea.

PMID- 29183062
TI  - Prescription Drug Monitoring Programs and Opioid Death Rates.

PMID- 29183063
TI  - Medical Specialty Board Finances.

PMID- 29183064
TI  - Medical Specialty Board Finances.

PMID- 29183065
TI  - Medical Specialty Board Finances.

PMID- 29183066
TI  - Outcomes of Positive Airway Pressure for Sleep Apnea-Reply.

PMID- 29183067
TI  - Prescription Drug Monitoring Programs and Opioid Death Rates-Reply.

PMID- 29183069
TI  - Romosozumab Prevents Fractures in Women With Osteoporosis.

PMID- 29183068
TI  - Medical Specialty Board Finances-Reply.

PMID- 29183070
TI  - Primary Care Treatment of Substance Use Disorder Reaches More Patients.

PMID- 29183071
TI  - Continuous Glucose Monitoring in Pregnant Women With Diabetes.

PMID- 29183072
TI  - Evolocumab Reduces Cardiovascular Risk Regardless of Diabetes Status.

PMID- 29183073
TI  - Psychosocial Intervention Improves Adherence to Antidepressants.

PMID- 29183074
TI  - Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation
      on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.
AB  - Importance: Fecal microbiota transplantation (FMT) is effective in preventing
      recurrent Clostridium difficile infection (RCDI). However, it is not known
      whether clinical efficacy differs by route of delivery. Objective: To determine
      whether FMT by oral capsule is noninferior to colonoscopy delivery in efficacy.
      Design, Setting, and Participants: Noninferiority, unblinded, randomized trial
      conducted in 3 academic centers in Alberta, Canada. A total of 116 adult patients
      with RCDI were enrolled between October 2014 and September 2016, with follow-up
      to December 2016. The noninferiority margin was 15%. Interventions: Participants
      were randomly assigned to FMT by capsule or by colonoscopy at a 1:1 ratio. Main
      Outcomes and Measures: The primary outcome was the proportion of patients without
      RCDI 12 weeks after FMT. Secondary outcomes included (1) serious and minor
      adverse events, (2) changes in quality of life by the 36-Item Short Form Survey
      on a scale of 0 (worst possible quality of life) to 100 (best quality of life),
      and (3) patient perception on a scale of 1 (not at all unpleasant) to 10
      (extremely unpleasant) and satisfaction on a scale of 1 (best) to 10 (worst).
      Results: Among 116 patients randomized (mean [SD] age, 58 [19] years; 79 women
      [68%]), 105 (91%) completed the trial, with 57 patients randomized to the capsule
      group and 59 to the colonoscopy group. In per-protocol analysis, prevention of
      RCDI after a single treatment was achieved in 96.2% in both the capsule group
      (51/53) and the colonoscopy group (50/52) (difference, 0%; 1-sided 95% CI, -6.1%
      to infinity; P < .001), meeting the criterion for noninferiority. One patient in
      each group died of underlying cardiopulmonary illness unrelated to FMT. Rates of
      minor adverse events were 5.4% for the capsule group vs 12.5% for the colonoscopy
      group. There was no significant between-group difference in improvement in
      quality of life. A significantly greater proportion of participants receiving
      capsules rated their experience as "not at all unpleasant" (66% vs 44%;
      difference, 22% [95% CI, 3%-40%]; P = .01). Conclusions and Relevance: Among
      adults with RCDI, FMT via oral capsules was not inferior to delivery by
      colonoscopy for preventing recurrent infection over 12 weeks. Treatment with oral
      capsules may be an effective approach to treating RCDI. Trial Registration:
      clinicaltrials.gov Identifier: NCT02254811.

PMID- 29183075
TI  - Chemical Composition and Labeling of Substances Marketed as Selective Androgen
      Receptor Modulators and Sold via the Internet.
AB  - Importance: Recent reports have described the increasing use of nonsteroidal
      selective androgen receptor modulators, which have not been approved by the US
      Food and Drug Administration (FDA), to enhance appearance and performance. The
      composition and purity of such products is not known. Objective: To determine the
      chemical identity and the amounts of ingredients in dietary supplements and
      products marketed and sold through the internet as selective androgen receptor
      modulators and compare the analyzed contents with product labels. Design and
      Setting: Web-based searches were performed from February 18, 2016, to March 25,
      2016, using the Google search engine on the Chrome and Internet Explorer web
      browsers to identify suppliers selling selective androgen receptor modulators.
      The products were purchased and the identities of the compounds and their amounts
      were determined from April to August 2016 using chain-of-custody and World Anti
      Doping Association-approved analytical procedures. Analytical findings were
      compared against the label information. Exposures: Products marketed and sold as
      selective androgen receptor modulators. Main Outcomes and Measures: Chemical
      identities and the amount of ingredients in each product marketed and sold as
      selective androgen receptor modulators. Results: Among 44 products marketed and
      sold as selective androgen receptor modulators, only 23 (52%) contained 1 or more
      selective androgen receptor modulators (Ostarine, LGD-4033, or Andarine). An
      additional 17 products (39%) contained another unapproved drug, including the
      growth hormone secretagogue ibutamoren, the peroxisome proliferator-activated
      receptor-delta agonist GW501516, and the Rev-ErbA agonist SR9009. Of the 44
      tested products, no active compound was detected in 4 (9%) and substances not
      listed on the label were contained in 11 (25%). In only 18 of the 44 products
      (41%), the amount of active compound in the product matched that listed on the
      label. The amount of the compounds listed on the label differed substantially
      from that found by analysis in 26 of 44 products (59%). Conclusions and
      Relevance: In this limited investigation involving chemical analyses of 44
      products marketed as selective androgen receptor modulators and sold via the
      internet, most products contained unapproved drugs and substances. Only 52%
      contained selective androgen receptor modulators and many were inaccurately
      labeled.

PMID- 29183077
TI  - Adherence to Methodological Standards in Research Using the National Inpatient
      Sample.
AB  - Importance: Publicly available data sets hold much potential, but their unique
      design may require specific analytic approaches. Objective: To determine
      adherence to appropriate research practices for a frequently used large public
      database, the National Inpatient Sample (NIS) of the Agency for Healthcare
      Research and Quality (AHRQ). Design, Setting, and Participants: In this
      observational study of the 1082 studies published using the NIS from January 2015
      through December 2016, a representative sample of 120 studies was systematically
      evaluated for adherence to practices required by AHRQ for the design and conduct
      of research using the NIS. Exposures: None. Main Outcomes and Measures: All
      studies were evaluated on 7 required research practices based on AHRQ's
      recommendations and compiled under 3 domains: (1) data interpretation
      (interpreting data as hospitalization records rather than unique patients); (2)
      research design (avoiding use in performing state-, hospital-, and physician
      level assessments where inappropriate; not using nonspecific administrative
      secondary diagnosis codes to study in-hospital events); and (3) data analysis
      (accounting for complex survey design of the NIS and changes in data structure
      over time). Results: Of 120 published studies, 85% (n = 102) did not adhere to 1
      or more required practices and 62% (n = 74) did not adhere to 2 or more required
      practices. An estimated 925 (95% CI, 852-998) NIS publications did not adhere to
      1 or more required practices and 696 (95% CI, 596-796) NIS publications did not
      adhere to 2 or more required practices. A total of 79 sampled studies (68.3% [95%
      CI, 59.3%-77.3%]) among the 1082 NIS studies screened for eligibility did not
      account for the effects of sampling error, clustering, and stratification; 62
      (54.4% [95% CI, 44.7%-64.0%]) extrapolated nonspecific secondary diagnoses to
      infer in-hospital events; 45 (40.4% [95% CI, 30.9%-50.0%]) miscategorized
      hospitalizations as individual patients; 10 (7.1% [95% CI, 2.1%-12.1%]) performed
      state-level analyses; and 3 (2.9% [95% CI, 0.0%-6.2%]) reported physician-level
      volume estimates. Of 27 studies (weighted; 218 studies [95% CI, 134-303])
      spanning periods of major changes in the data structure of the NIS, 21 (79.7%
      [95% CI, 62.5%-97.0%]) did not account for the changes. Among the 24 studies
      published in journals with an impact factor of 10 or greater, 16 (67%) did not
      adhere to 1 or more practices, and 9 (38%) did not adhere to 2 or more practices.
      Conclusions and Relevance: In this study of 120 recent publications that used
      data from the NIS, the majority did not adhere to required practices. Further
      research is needed to identify strategies to improve the quality of research
      using the NIS and assess whether there are similar problems with use of other
      publicly available data sets.

PMID- 29183078
TI  - Testing for BRCA1/2 Mutations.

PMID- 29183076
TI  - Association Between Wait Time and 30-Day Mortality in Adults Undergoing Hip
      Fracture Surgery.
AB  - Importance: Although wait times for hip fracture surgery have been linked to
      mortality and are being used as quality-of-care indicators worldwide, controversy
      exists about the duration of the wait that leads to complications. Objective: To
      use population-based wait-time data to identify the optimal time window in which
      to conduct hip fracture surgery before the risk of complications increases.
      Design, Setting, and Participants: Population-based, retrospective cohort study
      of adults undergoing hip fracture surgery between April 1, 2009, and March 31,
      2014, at 72 hospitals in Ontario, Canada. Risk-adjusted restricted cubic splines
      modeled the probability of each complication according to wait time. The
      inflection point (in hours) when complications began to increase was used to
      define early and delayed surgery. To evaluate the robustness of this definition,
      outcomes among propensity-score matched early and delayed surgical patients were
      compared using percent absolute risk differences (RDs, with 95% CIs). Exposure:
      Time elapsed from hospital arrival to surgery (in hours). Main Outcomes and
      Measures: Mortality within 30 days. Secondary outcomes included a composite of
      mortality or other medical complications (myocardial infarction, deep vein
      thrombosis, pulmonary embolism, and pneumonia). Results: Among 42 230 patients
      with hip fracture (mean [SD] age, 80.1 years [10.7], 70.5% women) who met study
      entry criteria, overall mortality at 30 days was 7.0%. The risk of complications
      increased when wait times were greater than 24 hours, irrespective of the
      complication considered. Compared with 13 731 propensity-score matched patients
      who received surgery earlier, 13 731 patients who received surgery after 24 hours
      had a significantly higher risk of 30-day mortality (898 [6.5%] vs 790 [5.8%]; %
      absolute RD, 0.79; 95% CI, 0.23-1.35) and the composite outcome (1680 [12.2%]) vs
      1383 [10.1%]; % absolute RD, 2.16; 95% CI, 1.43-2.89). Conclusions and Relevance:
      Among adults undergoing hip fracture surgery, increased wait time was associated
      with a greater risk of 30-day mortality and other complications. A wait time of
      24 hours may represent a threshold defining higher risk.

PMID- 29183079
TI  - Wrong-Site Surgery.

PMID- 29183081
TI  - Salt of the Earth.

PMID- 29183082
TI  - Hidradenitis Suppurativa: Advances in Diagnosis and Treatment.
AB  - Importance: Hidradenitis suppurativa (HS) is relatively common, with the
      prevalence of 0.05% to 4.10%, yet many patients receive inadequate treatment.
      Objective: To review the diagnosis, epidemiology, and treatment of HS with an
      emphasis on advances in the last 5 years. Evidence Review: A literature search
      was conducted using PubMed, MEDLINE (Medical Subject Headings [MeSH]), and EMBASE
      to include recently published treatment studies (searched from September 1, 2011,
      to May 1, 2017). Reviews, guidelines, conference abstracts, and studies with less
      than 10 patients were excluded. Furthermore, internet searches for guidelines on
      hidradenitis suppurativa using Baidu, Bing, Google, and Qwant browsers were
      performed. Findings: The diagnosis of HS is made by lesion morphology (nodules,
      abscesses, tunnels, and scars), location (axillae, inframammary folds, groin,
      perigenital, or perineal), and lesion progression (2 recurrences within 6 months
      or chronic or persistent lesions for >=3 months). HS is more common than was
      previously thought based on epidemiological analysis (0.05%-4.10%). Disability
      from HS can be significant. Patients with HS may have significant comorbidities
      (eg, obesity, metabolic syndrome, diabetes, and arthritis) and increased all
      cause mortality (incidence rate ratio, 1.35 [95% CI, 1.15-1.59]). Antibiotic
      treatment with combinations of clindamycin and rifampicin, or ertapenem followed
      by combination rifampicin, moxifloxacin, and metronidazole for 6 months is
      effective. Adalimumab is effective in a significant proportion of patients and
      treatment with IL-1 and IL-12 receptor subunit beta 1 (Rb1) antibodies may also
      be useful. Tissue-sparing surgical techniques and carbon dioxide laser treatments
      also are available, but the evidence on clinical outcomes with these approaches
      is limited. Conclusions and Relevance: Hidradenitis suppurativa is more common
      than previously thought and may be treated by an array of pharmacological and
      surgical techniques. Hidradenitis suppurativa should be considered in the
      differential diagnosis of nodular lesions or sinus tracts present in the axillae,
      groin, perineal, and mammillary fold regions.

PMID- 29183084
TI  - Suicide Rates Higher in Rural Areas for Most Demographic Groups.

PMID- 29183085
TI  - Pet Rats Infect Daughter, Mother With Hantavirus.

PMID- 29183086
TI  - Does Posterior Condylar Offset Affect Clinical Results following Total Knee
      Arthroplasty?
AB  - Total knee arthroplasty (TKA) is an effective, durable treatment for knee
      osteoarthritis. However, a subset of patients experiences incomplete pain relief
      and ongoing dysfunction. Posterior condylar offset (PCO) has previously been
      shown to be associated with postoperative range of motion (ROM) following TKA;
      however, an association with patient-reported outcome measures (PROMs) has not
      been established. The purpose of this study was to evaluate the association
      between PCO and postoperative ROM and PROMs. A retrospective review of 970
      posterior-stabilized single design TKAs was performed. Preoperative and
      postoperative radiographs were analyzed to measure the change in PCO and
      anteroposterior (AP) femoral dimension. Clinical outcome measures, including
      Short Form-12 physical and mental component summaries, Western Ontario and
      McMaster Universities Arthritis Index, and Knee Society Score were reviewed to
      determine if these were influenced by changes in PCO and AP dimension. PCO was
      increased by more than 3 mm in 15.1%, maintained (within 3 mm) in 59.6%, and
      decreased by more than 3 mm in 25.3% of patients. Comparing between these groups,
      there were no significant differences in postoperative ROM or PROM. AP dimension
      increased in 24.4%, maintained in 47.8%, and decreased in 27.8%. Similarly, there
      were no significant differences in ROM or PROM between these groups. Spearman's
      correlation analyses failed to identify an association between PCO and ROM or
      PROMs. In conclusion, increasing or decreasing PCO or AP femoral dimension with
      this PS TKA design did not significantly affect postoperative ROM or PROM.
      Similarly, maintenance of PCO within one implant size with this system compared
      with optimal sizing had no deleterious effect on TKA outcomes.

PMID- 29183087
TI  - Biomechanical Implications of an Oblique Knee Joint Line.
AB  - Surgical correction of multiapical deformities of the lower limb requires careful
      preoperative planning. Surgeons must account for the potential creation of
      secondary deformity, such as knee joint line obliquity, and the risks associated
      with accepting these changes in limb alignment. In this study, we evaluate the
      effect of knee joint obliquity on tibial plateau contact pressures and knee
      instability. Three cadaveric knees were dissected and put through biomechanical
      testing to simulate loading of an oblique knee joint. We observed < 1 mm femoral
      displacement (proxy measure of instability) between 15 degrees of varus tilt and
      10 degrees of valgus tilt, and greater increases in tibial plateau contact
      pressures with valgus tilt than with varus tilt. Our results suggest that, if the
      creation of a secondary coronal plane deformity at the knee joint cannot be
      avoided, up to 15 degrees of varus or 10 degrees of valgus alignment can be
      tolerated by an otherwise structurally normal knee.

PMID- 29183088
TI  - [Organ Donation in Victims of Non-Traumatic Out-of-Hospital Cardiac Arrest].
AB  - INTRODUCTION:  The out-of-hospital cardiac-arrest (OHCA) is one of the leading
      causes of death. However, although previous studies showed the possibility to
      transplant organs from resuscitated donors, organ donation following OHCA remains
      seldom. We therefore initiated this study to investigate the current percentage
      of organ donation in victims of OHCA in a german university hospital. MATERIAL
      AND METHODS:  We analyzed data from all victims of OHCA who were admitted to our
      hospital between January 1st 2008 and May 31st 2017. RESULTS:  Altogether, there
      were 385 victims of OHCA admitted to our hospital. 126 victims of OHCA (32.8 %)
      survived until hospital discharge, 259 died (67.2 %), hereunder 7 victims of OHCA
      (1.8 %) with proven brain death. 5 victims of OCHA (1.5 %) donated their organs,
      and altogether 14 organs could be transplanted successfully. DISCUSSION:  Organ
      donation following OHCA is seldom. We therefore would appreciate a more frequent
      diagnostics of brain death as currently not even all victims of OHCA with proven
      signs of brain damage in the computed tomography receive further diagnostics to
      confirm the diagnosis of brain death.

PMID- 29183089
TI  - Successful Treatment of Estrogen Excess in Primary Bilateral Macronodular
      Adrenocortical Hyperplasia with Leuprolide Acetate.
AB  - Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is an uncommon
      cause of adrenal Cushing syndrome (CS) in which cortisol and occasionally other
      steroid hormones can be secreted under the influence of aberrantly expressed G
      protein coupled receptors (GPCRs) in the adrenal cortex. We describe the unique
      case of a 64-year-old postmenopausal female with PBMAH whose adrenal lesions
      expressed luteinizing hormone receptors (LHr). She presented initially with CS
      and underwent right adrenalectomy; a few years later she presented with
      macromastia and mastodynia, possibly due to estrogen excess from her remaining
      left adrenocortical masses. Testing before and after treatment with quarterly
      leuprolide acetate therapy and immunohistochemistry on tissue and targeted
      sequencing of the genes of interest were performed. Tissue from the patient's
      right adrenal was tested for P450 aromatase (CYP19A1) and LHr expression; both
      were expressed throughout the hyperplastic cortex, although expression was more
      intense in the adenomatous areas. Targeted sequencing revealed a pathogenic
      PDE11A mutation, as well as variants in the ARMC5 and INHA genes. PDE11A
      expression was decreased in the adenoma but there was no loss of heterozygosity
      for the PDE11A locus. Because of the clinical presentation and LHr expression,
      quarterly leuprolide acetate therapy was started. Shortly after initiation of
      therapy, the patient reported decreased breast size and pain; she remains well
      controlled to date, after 10 years of treatment. This is the first description of
      a patient with PBMAH presenting with severe macromastia and mastodynia from what
      appears to be excess estrogen production from her adrenal tumor. The patient had
      a long-lasting response to chronic leuprolide acetate treatment, showing that
      drug therapy exploiting the aberrant receptor expression in PBMAH is possible
      even in the absence of cortisol overproduction.

PMID- 29183091
TI  - Systematic Review of the Epidemiology and Natural History of the Metabolic
      Vascular Syndrome and its Coincidence with Type 2 Diabetes Mellitus and
      Cardiovascular Diseases in Different European Countries.
AB  - The objectives of this systematic review were to estimate the incidence,
      prevalence and natural history of the metabolic (vascular) syndrome (MVS) among
      adults in different European countries. Furthermore, we assessed its co-incidence
      with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). PubMed, MedLine,
      and EMBASE (via Ovid) were searched for relevant studies. After reading 116 full
      text articles to find eligible ones, 66 publications met our inclusion criteria.
      Data for the incidence are based on a study from Portugal, in which the incidence
      rate for the MVS was 47.2/1000 person-years. Prevalence varied strongly depending
      on country and definition. The lowest was found in the United Kingdom (3%), the
      highest in Finland (71.7%). No article that deals with the natural history of the
      MVS was found. Considering the co-existence of MVS and T2DM, it ranged between 2%
      (United Kingdom) and 74.4% (Spain). The co-occurrence of MVS and CVD ranged from
      2.8% (Italy) up to 52% (Netherlands). Coronary heart disease (CHD) varied between
      1.2% and 44.2%. With regard to peripheral artery disease (PAD), values between
      3.3% and 59.8% were found. Due to the many different definitions of the MVS, a
      comparison is very difficult. Overall prevalence ranged between 3% and 71.7%
      depending on definition, age, and country. An association between MVS and T2DM as
      well as several CVD can be assumed.

PMID- 29183090
TI  - Serum Vitamin D Status, Vitamin D Receptor Polymorphism, and Glucose Homeostasis
      in Healthy Subjects.
AB  - Low vitamin D status has been frequently associated with impaired glucose
      metabolism. We examined associations between 25-hydroxyvitamin D (25-OH-D) and
      several parameters of glucose homeostasis in virtually healthy subjects, and
      explored possible interaction with vitamin D receptor (VDR) polymorphism.
      Nondiabetic subjects without chronic medication or any known significant manifest
      disease were selected from large general-population based population survey.
      Insulin sensitivity and beta cell secretion were calculated by homeostasis model
      assessment (HOMA) and soluble isoform of receptor for advanced glycation end
      products (sRAGE) using commercial ELISA. Subjects were also genotyped for
      rs2228570 polymorphism of VDR. After adjustment for potential confounders, we
      observed a significant relationship between 25-OH-D and fasting glycemia (beta
      coefficient=-5.904; p=0.002) or insulin sensitivity (beta=0.042; p=0.001), but
      not with beta cell secretion or sRAGE. We found also an interaction with VDR
      polymorphism. Subjects with low 25-OH-D and AA genotype had significantly lower
      insulin sensitivity than those with GG genotype plus highest 25-OH-D
      concentrations (107.3% vs. 183.9%, p=0.021). In conclusion, low vitamin D status
      was in virtually healthy subjects associated with decreased insulin sensitivity,
      namely in those with GG genotype of rs2228570 VDR polymorphism.

PMID- 29183092
TI  - [Methamphetamine Consumption During Pregnancy and its Effects on Neonates].
AB  - OBJECTIVE:  Methamphetamine (MA) has become one of the most commonly used illegal
      drugs during pregnancy. We sought to determine how MA abuse modifies pregnancy
      outcomes and the health of the newborn infants. Patients 102 newborns from
      mothers with antenatal MA consumption were admitted to the University Hospital
      Leipzig from 2004-2015. METHODS:  The effects of MA abuse on pregnancy outcomes
      and neonates were researched in a retrospective controlled study. We analysed the
      date of pregnancy detection, number of antenatal preventive examinations, body
      measurements of the neonates, duration of hospitalization, rate of preterm
      infants, congenital malformations and symptoms of neonatal abstinence syndrome.
      RESULTS:  The majority of pregnancies of MA abusing women were diagnosed during
      the 2. trimester and they had a median of 4 prenatal care visits. The group of MA
      exposed neonates includes twice as many preterm neonates as the control group
      (MA:20,6%; CG:10,7%). The consumption was associated with intrauterine growth
      restriction, an increased incidence of poor cardio respiratory adaptation,
      cardiac defects and a floppy muscle tone. The median time of hospitalization was
      10d as compared to a control group (CG:5d). Special care was needed in 44% of the
      neonates (CG:0,98%). The median age of primiparous women was 22.5 yr (CG:30 yr),
      4.9% were married (CG:38%). 57 of 102 women were unemployed. CONCLUSION:  Because
      of the adverse effects of perinatal MA abuse a multidisciplinary team is
      necessary to detect the consumption, to alleviate side effects and to provide
      efficient medical care for the newborns. Psychological and social support for the
      families are also important.

PMID- 29183093
TI  - Multiple Sclerosis with Onset Younger Than 10 Years in Turkey.
AB  - OBJECTIVE: To identify the demographics, clinical characteristics, disease
      course, treatment patterns, and disability levels of multiple sclerosis (MS)
      patients with onset under the age of 10 years (early onset multiple sclerosis,
      EOMS). METHODS: EOMS patients were reviewed retrospectively in detailed records
      from 27 child neurology centers. Patients with preschool (<=7 years) and school
      age (>7 years) onset were compared. RESULTS: There were 30 children (16 girls, 14
      boys) who have disease onset between 4 and 10 (mean8.1 +/- 1.8) years. MS was
      relapsing-remitting in 29 (96.7%) and primary progressive in one (3.3%) of the
      patients. In patients with onset <=7 years, motor symptoms (54.5%) and
      encephalopathy (45.5%) predominated, while in those with onset >7 years brainstem
      (42.1%), sensory (26.3%), and optic nerve (26.3%) involvement were the most
      frequent presentations. CONCLUSIONS: MS starting <=7 years differs from the 7-10
      year-old group by the higher rate of motor symptoms and more attacks in the first
      year: the latter suggests a more inflammatory character for EOMS.

PMID- 29183094
TI  - Impact of Intended Mode of Delivery on Outcomes in Preterm Growth-Restricted
      Fetuses.
AB  - BACKGROUND:  Scheduled cesarean is frequently performed for fetal growth
      restriction due to concerns for fetal intolerance of labor. OBJECTIVE:  We
      compared neonatal outcomes in preterm growth-restricted fetuses by intended mode
      of delivery. STUDY DESIGN:  We performed a retrospective cohort study of
      indicated preterm births with prenatally diagnosed growth restriction from 2011
      to 2014 at a single institution. Patients were classified by intended mode of
      delivery. The primary outcome was a composite of adverse neonatal outcomes,
      including perinatal death, cord blood acidemia, chest compressions during
      neonatal resuscitation, seizures, culture-proven sepsis, necrotizing
      enterocolitis, and grade III-IV intraventricular hemorrhage. Secondary analysis
      was performed examining the impact of umbilical artery Dopplers. RESULTS:  Of 101
      fetuses with growth restriction, 75 underwent planned cesarean deliveries. Of
      those induced, 46.2% delivered vaginally. Delivery by scheduled cesarean was not
      associated with a decreased risk of the composite outcome (adjusted odds ratio
      [aOR], 1.61; 95% confidence interval [CI], 0.45-5.78), even when only those with
      abnormal umbilical artery Dopplers were considered (aOR, 2.8; 95% CI, 0.40-20.2).
      CONCLUSION:  In this cohort, planned cesarean was not associated with a reduction
      in neonatal morbidity, even when considering only those with abnormal umbilical
      artery Dopplers. In otherwise appropriate candidates for vaginal delivery, fetal
      growth restriction should not be considered a contraindication to trial of labor.

PMID- 29183095
TI  - The Independent Contribution of Uterine Blood Flow to Birth Weight and Body
      Composition in Smoking Mothers.
AB  - OBJECTIVE:  This study aims to evaluate the relationship of maternal smoking to
      uterine artery hemodynamics and examine independent contributions to birth weight
      and fetal body composition. STUDY DESIGN:  Women were enrolled in a prospective
      randomized controlled study targeting smoking abstinence. Uterine artery Doppler
      ultrasound was performed and volumetric blood flow was calculated. Third
      trimester ultrasound estimates of fetal body composition were performed and birth
      weight was recorded. RESULTS:  Uterine artery volumetric flow and resistance
      index (RI) were significantly correlated with birth weight adjusted for
      gestational age (R = 0.35, p = 0.002; R = - 0.27, p = 0.02). Volumetric flow was
      significantly associated with fetal fat mass (R = 0.30, p = 0.018). Smoking
      status did not have significant effects on lean body mass (t [61] = 0.60, p =
      0.55), fat mass (t [61] = 1.67, p = 0.10), or volumetric flow (t = 0.86, df = 87,
      p = 0.39). Stepwise regression identified volumetric flow (beta = 0.81, 95%
      confidence interval [CI]: 0.35-1.27, p < 0.001), maternal prepregnancy body mass
      index (beta = 16.04, 95% CI: 2.57-29.50, p = 0.02), and fetal sex (beta = 346.28,
      95% CI: -532.64 to 159.91, p < 0.001, where male = 0 and female = 1) as
      independent contributors to birth weight adjusted for gestational age.
      CONCLUSION:  No direct relationship of smoking to uterine artery hemodynamics was
      demonstrated. Volumetric flow was an independent contributor to birth weight and
      was associated with fetal fat deposition, while smoking was not independently
      associated with either outcome.

PMID- 29183096
TI  - Morbidity Associated with Fetal Macrosomia among Women with Diabetes Mellitus.
AB  - OBJECTIVE:  This article aims to compare the composite maternal and neonatal
      morbidities (CMM and CNM, respectively) between macrosomic (>=4,000 g) and
      nonmacrosomic (<4,000 g) newborns among women with diabetes mellitus (DM).
      METHODS:  Maternal demographic and peripartum outcome data (N = 1,260) were
      collected from a retrospective cohort. CMM included
      chorioamnionitis/endometritis, wound infection, shoulder dystocia, eclampsia,
      pulmonary edema, admission for hypoglycemia, 3rd/4th degree perineal laceration,
      and death. CNM included 5-minute Appearance, Pulse, Grimace, Activity and
      Respiration (APGAR) score of <4, neonatal intensive care unit (NICU) admission,
      respiratory distress syndrome, mechanical ventilation, intraventricular
      hemorrhage grade III/IV, necrotizing enterocolitis stage II/III, hypoglycemia,
      hypocalcemia, bronchopulmonary dysplasia, sepsis, seizures, hyperbilirubinemia,
      and death. Multivariable Poisson regression models with robust error variance
      were used to calculate adjusted relative risk (aRR) and 95% confidence interval
      (CI). RESULTS:  The study population consisted of 967 subjects, including 854
      (88.3%) nonmacrosomic and 113 (11.7%) macrosomic infants. After adjustment, the
      risk of CMM was higher among macrosomic deliveries (aRR = 4.08, 95% CI = 2.45
      6.80). The risk of CNM was also higher among macrosomic deliveries (aRR = 1.77,
      95% CI = 1.39-2.24). Macrosomia was associated with an increased risk in NICU
      admission, hypoglycemia, and hyperbilirubinemia. CONCLUSION:  Among DM
      deliveries, macrosomia was associated with a fourfold higher risk of CMM and
      almost twofold higher risk of CNM.

PMID- 29183097
TI  - Predictors of PDA Treatment in Preterm Neonates Who Had Received Prophylactic
      Indomethacin.
AB  - OBJECTIVE:  To identify clinical factors those predict the need for patent ductus
      arteriosus (PDA) treatment in preterm neonates who had received prophylactic
      indomethacin. PATIENTS AND METHODS:  Preterm neonates with <28 weeks' gestational
      age admitted to level III neonatal intensive care units (NICUs) in Canada between
      2010 and 2015 and who had received prophylactic indomethacin were included.
      Primary outcome was surgical ligation of PDA, while secondary outcomes were any
      PDA treatment and common neonatal morbidities. RESULTS:  Of the 7,024 eligible
      neonates, 843 (12%) neonates had received prophylactic indomethacin. Of them, 84
      neonates (10%) required surgical ligation while 367 neonates (44%) received
      medical or surgical treatment for PDA. Logistic regression analyses identified
      gestational age (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.58-0.87)
      and outborn status (OR: 2.07, 95% CI: 1.09-3.93) as predictors for surgical
      ligation. Maternal hypertension (OR: 0.57, 95% CI: 0.37-0.89), rupture of
      membranes (ROM) >=24 hours (OR: 0.68, 95% CI: 0.48-0.96), and surfactant
      treatment (OR: 1.70, 95% CI: 1.09-2.66) were predictors for medical or surgical
      treatment of PDA. CONCLUSION:  In extremely preterm neonates who had received
      prophylactic indomethacin, gestational age and outborn status were predictors for
      surgical ligation of PDA, while maternal hypertension, ROM >=24 hours, and
      surfactant treatment were associated with the medical or surgical treatment of
      PDA.

PMID- 29183098
TI  - Ultrasound-Guided Cannulation of the Brachiocephalic Vein in Neonates and Preterm
      Infants: A Prospective Observational Study.
AB  - INTRODUCTION:  Percutaneous central venous catheter (CVC) insertion is a
      challenging procedure in neonates, especially in preterm infants. OBJECTIVE: 
      This study aims to describe the technical success and safety profile of
      ultrasound (US)-guided brachiocephalic vein (BCV) cannulation in neonates.
      METHODS:  Prospective observational study. Neonates admitted to the neonatal
      intensive care unit (NICU) in whom US-guided cannulation of the BCV was attempted
      were eligible. Outcomes included first attempt success rate, the overall success
      rate, the number of attempts, the cannulation time, immediate mechanical
      complications, catheter indwelling days, and late complications. RESULTS:  A
      total of 40 procedures in 37 patients were included. Median weight and age at the
      time of cannulation were 1.85 kg (0.76-4.8) and 13 days (3-31), respectively.
      First attempt and overall success rates were 29 (72.5%) and 38 (95%),
      respectively. No major complications were observed. Catheter-associated infection
      rate was 2.4/1,000 catheter days. There were no difference in outcomes between
      low weight preterm infants (<1.5 kg) and the rest of the cohort. There was no
      linear relationship between weight at time of insertion and the number of
      puncture attempts (r = 0.250; p = 0.154) or cannulation time (r = 0.257; p =
      0.142). CONCLUSION:  US-guided cannulation of the BCV may be considered in
      acutely ill neonates, including small preterm infants, who need a large bore CVC.

PMID- 29183099
TI  - Neonatal Outcomes Differ after Spontaneous and Indicated Preterm Birth.
AB  - OBJECTIVE:  Preterm birth (PTB) at <37 weeks of gestation complicates 10% of
      pregnancies and requires accurate counseling regarding anticipated neonatal
      outcomes. PTB classification as spontaneous or indicated is commonly used to
      cluster PTB into subtypes, but whether neonatal outcomes differ by PTB subtype is
      unknown. We tested the hypothesis that neonatal morbidity differs based on
      subtype of PTB. METHODS:  We performed a retrospective cohort study of live-born,
      non-anomalous preterm infants from 2004 to 2008. Spontaneous PTB was defined as
      PTB from spontaneous preterm labor or preterm rupture of membranes. Indicated PTB
      was defined as PTB from any maternal or fetal medical complication necessitating
      delivery. The primary outcome was a composite of early respiratory morbidity.
      Secondary outcomes included late composite respiratory morbidity and other
      neonatal morbidities. RESULTS:  Of 1,223 preterm neonates, 60.9% were born after
      spontaneous PTB and 30.1% after indicated PTB. Composite early respiratory
      morbidity was significantly higher after indicated PTB versus spontaneous PTB
      (1.3, 95% confidence interval [CI] 1.2-1.4). Composite late respiratory morbidity
      (1.8, 95% CI 1.3-2.3) and neonatal death (2.8, 95% CI 1.5-5.1) were also
      significantly higher after indicated PTB versus spontaneous PTB. CONCLUSION: 
      Neonatal respiratory outcomes and death differ according to PTB subtype. PTB
      subtype should be considered while counseling families and anticipating neonatal
      outcomes after PTB.

PMID- 29183100
TI  - [Access to Inpatient Rehabilitation of Methamphetamine Addiction - Barriers and
      Potential for Improvement from the Experts' Perspective].
AB  - Objective The study explores central barriers impeding the access to inpatient
      rehabilitation of methamphetamine addicts and investigates how these barriers can
      be tackled. Methods The experiences and perspectives of experts from different
      healthcare sectors were explored within 39 semi-structured individual interviews.
      Subsequently, the results gathered in the course of the individual interviews
      were discussed within 2 inter-professional focus groups. All interviews and focus
      group discussions were analyzed according to the interpretive analysis method of
      Meuser & Nagel. Results Structural issues in particular impair the access to
      inpatient rehabilitation of methamphetamine dependents. This includes impeded
      access to rehabilitation via general practitioners, rare implementation of
      seamless transitions, capacity problems as well as non-transparent procedures in
      terms of treatment facility allocations. Conclusion Various barriers impair
      access to inpatient rehabilitation of methamphetamine dependents. It is important
      to increase awareness of methamphetamine addicts and their specific needs
      particularly among general practitioners. Furthermore, it is important to ensure
      seamless transitions from detoxification treatment to inpatient rehabilitation
      and to reduce waiting periods as well as to provide well-differentiated and
      appropriate rehabilitation options.

PMID- 29183101
TI  - [The Significance of Work Motivation for Rehabilitation Success].
AB  - AIM OF THIS STUDY: Apart from the reduction of symptoms and the restoration of
      working ability, return to work is a long-term goal of medical rehabilitation.
      The aim of this study is to analyze the influence of work motivation on the
      outcome of rehabilitation. METHODS: The data basis consists of N=998 patients at
      the psychosomatic department of the Oberharz Rehabilitation Center as well as
      data from insurance accounts. Using multiple linear regression analysis the
      predictive power of work motivation on rehabilitation outcome as well as
      different facets of work motivation in their function as predictors are analyzed.
      RESULTS: Only minor statistical relations could be found between work motivation
      and rehabilitation success when also taking employment status of the previous
      year and subjective vocational disability into account. A small predictive power
      can be attributed to work motivation as a factor in rehabilitation success in the
      sense of a reduction of symptoms. Particular facets of work motivation are
      suitable to predict rehabilitation success. Patients with a work motivation risk
      profile differ from patients with a normal work motivation profile as regards
      their capacity to work in the year following rehabilitation treatment.
      CONCLUSION: Work motivation represents a relevant construct in rehabilitation
      success but is strongly influenced by individual factors. During rehabilitation,
      individual problems which influence work motivation should be taken into account
      more strongly.

PMID- 29183102
TI  - [Spectrum and Frequency of ADHD-Related Symptoms and Minimal Cerebral Brain
      Dysfunctions in Psychosomatic Inpatients].
AB  - Objective ADHD (attention deficit hyperactivity disorders) and MCD (minimal
      cerebral dysfunctions) can impair participation. They pose difficult diagnostic
      problems. Aim of the present study has been to describe the frequency and the
      spectrum of ADHD and MCD in psychosomatic inpatients. Methods 1453 psychosomatic
      inpatients filled in the ADHS-SB and the MCD-TLS-FB screening for self-reported
      ADHD and minimal cerebral dysfunctions. Prevalence rates were calculated
      depending on different intensities of symptoms. Results According to the ADHS-SB
      49.5% of the patients met the criteria of an adult ADHD when taking all
      intensities of symptoms into account. The prevalence rate decreases to 14,6% if
      moderate to severe symptoms and to 1% if only severe symptoms ratings were
      recognized. Additional to core symptoms of attentions deficit and hyperactivity
      patients with ADHD reported about problems with orientation, memory, cognition,
      emotion regulation, vegetative stability and movement. Discussion ADHD-related
      symptoms and minimal cerebral dysfunctions are frequently seen in psychosomatic
      inpatients. In clinical practice the full spectrum of TLS must be taken into
      account as they all can impair participation depending on context requirements.

PMID- 29183103
TI  - [ICF-Checklist to Evaluate Inclusion of Elderlies with Intellectual Disability -
      Psychometric Properties].
AB  - Background An instrument should have been developed to measure participation as
      one possible criterion to evaluate inclusion of elderly people with intellectual
      disability. The ICF was utilized, because participation is one part of health
      related functioning, respectively disability. Furthermore ICF includes
      environmental factors (contextual factors) and attaches them an essentially
      influence on health related functioning, in particular on participation. Thus ICF
      Checklist additionally identifies environmental barriers for elimination.
      Methodology A linking process with VINELAND-II yielded 138 ICF items for the
      Checklist. The sample consists of 50 persons with a light or moderate
      intellectual disability. Two-thirds are female and the average age is 68. They
      were directly asked about their perceived quality of life. Additionally, proxy
      interviews were carried out with responsible staff members concerning necessary
      support and behavioral deviances. The ICF Checklist was administered twice, once
      (t2) the current staff member should rate health related functioning at the given
      time and in addition, a staff member who knows the person at least 10 years
      before (t1) should rate the former functioning. Content validity was investigated
      with factor analysis and criterion validity with correlational analysis related
      to supports need, behavioral deviances and perceived quality of life.
      Quantitative analysis was validated by qualitative content analysis of patient
      documentation. Results Factor analysis shows logical variable clusters across the
      extracted factors but neither interpretable factors. The Checklist is reliable,
      valid related to the chosen criterions and shows the expected age-related shifts.
      Qualitative analysis corresponds with quantitative data. Consequences/Conclusion
      ICF Checklist is appropriate to manage and evaluate patient-centered care.

PMID- 29183104
TI  - Prevalence and Progression Rate of Diabetic Retinopathy in Type 2 Diabetes
      Patients in Correlation with the Duration of Diabetes.
AB  - AIMS: We examined prevalence and progression of retinopathy in dependence on
      diabetes duration in order to estimate the probability of progression.
      PATIENTS/METHODS: In a retrospective cohort-analysis from an academic outpatient
      department of endocrinology and metabolic diseases we analyzed 17461
      consultations of 4513 patients with DM2 from 1987 to 2014. 50.3% of the patients
      (n=2272) had at least one documented result of funduscopy. RESULTS: 25.8% of the
      patients had retinopathy (20.2% non-proliferative, 4.7% proliferative, 0.7% were
      not classified, 0.1% blindness). The prevalence of retinopathy in dependence on
      diabetes duration was 1.1% at diagnosis, 6.6% after 0<5 years, 12% after 5<10
      years, 24% after 10<15 years, 39.9% after 15<20 years, 52.7% after 20<25 years,
      58.7% after 25<30 years and 63% after >=30 years. In a subset of 586 (25.7%)
      patients with retinal photography of 3 consecutive years 7.0% showed
      deterioration after one and 12.2% after two years; 2.6% improved after one and
      2.8% after two years. 201 (34.3%) of this group had<10 years diabetes and lower
      deterioration (4.5% worsened after one and 9.5% after two years). Their
      retinopathy mainly transformed from no retinopathy to non-proliferative. Four
      patients (2.0%) developed proliferative retinopathy. CONCLUSIONS/INTERPRETATIONS:
      Within the first 10 years of diabetes duration, the prevalence of retinopathy is
      low and the progression infrequent. Most patients have a non-proliferative form
      which can be reversible and rarely requires interventions. Patients with DM2
      without retinopathy and good glycaemic control do not run into additional risk
      from expanding funduscopy intervals to biennial.

PMID- 29183105
TI  - Relation of Carotid Artery Plaque to Coronary Heart Disease and Stroke in Chinese
      Patients: Does Hyperglycemia Status Matter?
AB  - OBJECTIVE: To examine the association of carotid artery plaque with the incident
      coronary heart disease and stroke events in Chinese patients and explore whether
      the association differs between patients with and without hyperglycemia. METHODS:
      We evaluated plaque, and blood pressure, total cholesterol, triglycerides, high
      density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting
      serum insulin, fasting plasma glucose, 2 h postprandial glucose and Homeostasis
      model assessment of insulin resistance in 253 Chinese patients. T-test and X2
      test were used to compare the clinical characteristics and Binary logistic
      regression was applied to analyze the association of coronary heart disease and
      stroke between patients with and without hyperglycemia. RESULTS: Among 253
      patients, 162 patients had hyperglycemia (i. e., diabetes, impaired glucose
      regulation and stress induced hyperglycemia) and 155 (61.3%) patients had plaque.
      Fasting plasma glucose, 2 h postprandial glucose and Homeostasis model assessment
      of insulin resistance, triglycerides, plaque were significantly higher in the
      hyperglycemia group than non-hyperglycemia. The incident coronary heart disease
      and stroke events in patients with plaque were 2.254 (95%CI,1.203-4.224) and
      2.437 (95%CI,1.042-5.701) times higher than those without plaque, respectively.
      Among hyperglycemia subgroup, plaque was an independent risk factor for coronary
      heart disease (OR,3.075,95%CI,1.353-6.992) and stroke (OR,3.571,95%CI,1.460
      8.737). The slopes (associations between coronary heart disease/stroke and
      plaque) were steeper in the hyperglycemia group than those in the non
      hyperglycemia group (coronary heart disease OR,3.075 vs. 2.614; stroke OR,3.571
      vs. 3.307). CONCLUSIONS: The incident coronary heart disease and stroke events in
      patients with plaque were higher than those without plaque, and this difference
      was more pronounced for patients with hyperglycemia vs. those without
      hyperglycemia.

PMID- 29183106
TI  - Monogenic Diabetes Not Caused By Mutations in Mody Genes: A Very Heterogenous
      Group of Diabetes.
AB  - Monogenic diabetes represents a heterogeneous group of disorders resulting from a
      single gene defect leading to disruption of insulin secretion or a reduction in
      the number of beta cells. Despite the classification of monogenic diabetes into
      neonatal diabetes or maturity onset diabetes of the young (MODY) according to age
      of onset, not every case can be classified into those 2 groups. We evaluated
      patients with monogenic diabetes diagnosed during the last 10 year period. Type 1
      DM, MODY, and patients with negative autoantibodies and no mutation in a known
      gene were excluded from the study. Thirteen patients were diagnosed with
      monogenic diabetes in Department of Pediatric Endocrinology, Ankara University
      School of Medicine, Ankara, Turkey. Five of them were diagnosed after 6 months of
      age. Five had a KATP channel defect. Mutations in genes resulting in destruction
      of beta cells were detected in 7 patients, with 4 cases having a WFS, 2 an LRBA,
      and one a IL2RA mutation. Additional systemic findings were seen in 6/13
      patients, with 5/6 having severe immune system dysfunction. Treatment with
      sulphonylurea was successful in two patients.. The other patients were given
      insulin in differing doses. Four patients died during follow-up, three of which
      had immune system dysfunction. Monogenic diabetes can be diagnosed after 6 months
      of age, even with positive autoantibodies. Immune dysfunction was a common
      feature in our cohort and should be investigated in all patients with early-onset
      monogenic diabetes. Mortality of patients with monogenic diabetes and additional
      autoimmunity was high in our cohort and is likely to reflect the multisystem
      nature of these diseases.

PMID- 29183107
TI  - Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro
      inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and
      subfertility.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by infrequent or
      absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia).
      Hyperinsulinaemia occurs secondary to insulin resistance and is associated with
      increased risk of cardiovascular disease and diabetes mellitus. Insulin
      sensitising agents such as metformin may be effective in treating PCOS-related
      anovulation. OBJECTIVES: To evaluate the effectiveness and safety of insulin
      sensitising drugs in improving reproductive and metabolic outcomes for women with
      PCOS undergoing ovulation induction. SEARCH METHODS: We searched the following
      databases from inception to January 2017: Cochrane Gynaecology and Fertility
      Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. We
      searched registers of ongoing trials and reference lists from relevant studies.
      SELECTION CRITERIA: We included randomised controlled trials of insulin
      sensitising drugs compared with placebo, no treatment, or an ovulation-induction
      agent for women with oligo and anovulatory PCOS. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed studies for eligibility and bias.
      Primary outcomes were live birth rate and gastrointestinal adverse effects.
      Secondary outcomes included other pregnancy outcomes, menstrual frequency and
      metabolic effects. We combined data to calculate pooled odds ratios (ORs) and 95%
      confidence intervals (CIs). We assessed statistical heterogeneity using the I2
      statistic and reported quality of the evidence for primary outcomes using GRADE
      methodology. MAIN RESULTS: We assessed the interventions metformin, clomiphene
      citrate, metformin plus clomiphene citrate, D-chiro-inositol, rosiglitazone and
      pioglitazone. We compared these with each other, placebo or no treatment. We
      included 48 studies (4451 women), 42 of which investigated metformin (4024
      women). Evidence quality ranged from very low to moderate. Limitations were risk
      of bias (poor reporting of methodology and incomplete outcome data), imprecision
      and inconsistency. Metformin versus placebo or no treatmentThe evidence suggests
      that metformin may improve live birth rates compared with placebo (OR 1.59, 95%
      CI 1.00 to 2.51, 4 studies, 435 women, I2 = 0%, low-quality evidence). The
      metformin group experienced more gastrointestinal side effects (OR 4.76, 95% CI
      3.06 to 7.41, 7 studies, 670 women, I2 = 61%, moderate-quality evidence) but had
      higher rates of clinical pregnancy (OR 1.93, 95% CI 1.42 to 2.64, 9 studies, 1027
      women, I2 = 43%, moderate-quality evidence), ovulation (OR 2.55, 95% CI 1.81 to
      3.59, 14 studies, 701 women, I2 = 58%, moderate-quality evidence) and menstrual
      frequency (OR 1.72, 95% CI 1.14 to 2.61, 7 studies, 427 women, I2 = 54%, low
      quality evidence). There was no clear evidence of a difference in miscarriage
      rates (OR 1.08, 95% CI 0.50 to 2.35, 4 studies, 748 women, I2 = 0%, low-quality
      evidence). Metformin plus clomiphene citrate versus clomiphene citrate alone
      There was no conclusive evidence of a difference between the groups in live birth
      rates (OR 1.21, 95% CI 0.92 to 1.59, 9 studies, 1079 women, I2 = 20%, low-quality
      evidence), but gastrointestinal side effects were more common with combined
      therapy (OR 3.97, 95% CI 2.59 to 6.08, 3 studies, 591 women, I2 = 47%, moderate
      quality evidence). However, the combined therapy group had higher rates of
      clinical pregnancy (OR 1.59, 95% CI 1.27 to 1.99, 16 studies, 1529 women, I2 =
      33%, moderate-quality evidence) and ovulation (OR 1.57, 95% CI 1.28 to 1.92, 21
      studies, 1624 women, I2 = 64%, moderate-quality evidence). There was a
      statistically significant difference in miscarriage rate per woman, with higher
      rates in the combined therapy group (OR 1.59, 95% CI 1.03 to 2.46, 9 studies,
      1096 women, I2 = 0%, low-quality evidence) but this is of uncertain clinical
      significance due to low-quality evidence, and no clear difference between groups
      when we analysed miscarriage per pregnancy (OR 1.30, 95% CI 0.80 to 2.12, 8
      studies; 400 pregnancies, I2 = 0%, low-quality evidence). Metformin versus
      clomiphene citrateWhen all studies were combined, findings for live birth were
      inconclusive and inconsistent (OR 0.71, 95% CI 0.49 to 1.01, 5 studies, 741
      women, I2 = 86%, very low-quality evidence). In subgroup analysis by obesity
      status, obese women had a lower birth rate in the metformin group (OR 0.30, 95%
      CI 0.17 to 0.52, 2 studies, 500 women, I2 = 0%, very low-quality evidence), while
      data from the non-obese group showed a possible benefit from metformin, with high
      heterogeneity (OR 1.71, 95% CI 1.00 to 2.94, 3 studies, 241 women, I2 = 78%, very
      low-quality evidence). Similarly, among obese women taking metformin there were
      lower rates of clinical pregnancy (OR 0.34, 95% CI 0.21 to 0.55, 2 studies, 500
      women, I2 = 0%, very low-quality evidence) and ovulation (OR 0.29, 95% CI 0.20 to
      0.43 2 studies, 500 women, I2 = 0%, low-quality evidence) while among non-obese
      women, the metformin group had more pregnancies (OR 1.56, 95% CI 1.05 to 2.33, 5
      studies, 490 women, I2 = 41%, very low-quality evidence) and no clear difference
      in ovulation rates (OR 0.81, 95% CI 0.51 to 1.28, 4 studies, 312 women, low
      quality evidence, I2=0%). There was no clear evidence of a difference in
      miscarriage rates (overall: OR 0.92, 95% CI 0.50 to 1.67, 5 studies, 741 women,
      I2 = 52%, very low-quality evidence). D-chiro-inositol (2 studies), rosiglitazone
      (1 study) or pioglitazone (1 study) versus placebo or no treatmentWe were unable
      to draw conclusions regarding other insulin-sensitising drugs as no studies
      reported primary outcomes. AUTHORS' CONCLUSIONS: Our updated review suggests that
      metformin alone may be beneficial over placebo for live birth, although the
      evidence quality was low. When metformin was compared with clomiphene citrate,
      data for live birth were inconclusive, and our findings were limited by lack of
      evidence. Results differed by body mass index (BMI), emphasising the importance
      of stratifying results by BMI. An improvement in clinical pregnancy and ovulation
      suggests that clomiphene citrate remains preferable to metformin for ovulation
      induction in obese women with PCOS.An improved clinical pregnancy and ovulation
      rate with metformin and clomiphene citrate versus clomiphene citrate alone
      suggests that combined therapy may be useful although we do not know whether this
      translates into increased live births. Women taking metformin alone or with
      combined therapy should be advised that there is no evidence of increased
      miscarriages, but gastrointestinal side effects are more likely.

PMID- 29183108
TI  - Enhanced Efficiency and Long-Term Stability of Perovskite Solar Cells by
      Synergistic Effect of Nonhygroscopic Doping in Conjugated Polymer-Based Hole
      Transporting Layer.
AB  - A face-on oriented and p-doped semicrystalline conjugated polymer, poly[(2,5
      bis(2-hexyldecyloxy)phenylene)-alt-(5,6-difluoro-4,7-di(thiophen-2
      yl)benzo[c][1,2,5]-thiadiazole)] (PPDT2FBT), was studied as a hole-transport
      layer (HTL) in methylammonium lead triiodide-based perovskite solar cells
      (PVSCs). PPDT2FBT exhibits a mid-band gap (1.7 eV), high vertical hole mobility
      (7.3 * 10-3 cm2/V.s), and well-aligned frontier energy levels with a perovskite
      layer for efficient charge transfer/transport, showing a maximum power conversion
      efficiency (PCE) of 16.8%. Upon doping the PPDT2FBT HTL with a nonhygroscopic
      Lewis acid, tris(pentafluorophenyl)borane (BCF, 2-6 wt %), the vertical
      conductivity was improved by a factor of approximately 2, and the resulting PCE
      was further improved up to 17.7%, which is higher than that of standard PVSCs
      with 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro
      OMeTAD) as an HTL. After BCF doping, the clearly enhanced carrier diffusion
      coefficient, diffusion length, and lifetime were measured using intensity
      modulated photocurrent and photovoltage spectroscopy. Furthermore, compared to
      the standard PVSCs with spiro-OMeTAD, the temporal device stability was
      remarkably improved, preserving the ~60% of the original PCE for 500 h without
      encapsulation under light-soaking condition (1 sun AM 1.5G) at 85  degrees C and
      85% humidity, which is mainly due to the highly crystalline conjugated backbone
      of PPDT2FBT and nonhygroscopic nature of BCF. In addition, formamidinium lead
      iodide/bromide (FAPbI3-xBrx)-based PVSCs with the BCF-doped PPDT2FBT as an HTL
      was also prepared to show 18.8% PCE, suggesting a wide applicability of PPDT2FBT
      HTL for different types of PVSCs.

PMID- 29183109
TI  - Palladium-Catalyzed Dearomative syn-1,4-Carboamination.
AB  - A dearomative 1,4-carboamination of arenes has been achieved using arenophile
      cycloaddition and subsequent palladium-catalyzed substitution with nonstabilized
      lithium enolates. This protocol delivers products with exclusive syn-1,4
      selectivity and can be also conducted in an asymmetric fashion. The method allows
      rapid dearomative difunctionalization of simple aromatic compounds into
      functional small molecules amenable to further diversification.

PMID- 29183110
TI  - Hyaluronic Acid-Based pH-Sensitive Polymer-Modified Liposomes for Cell-Specific
      Intracellular Drug Delivery Systems.
AB  - For the enhancement of therapeutic effects and reduction of side effects derived
      from anticancer drugs in cancer chemotherapy, it is imperative to develop drug
      delivery systems with cancer-specificity and controlled release function inside
      cancer cells. pH-sensitive liposomes are useful as an intracellular drug delivery
      system because of their abilities to transfer their contents into the cell
      interior through fusion or destabilization of endosome, which has weakly acidic
      environment. We earlier reported liposomes modified with various types of pH
      sensitive polymers based on synthetic polymers and biopolymers as vehicles for
      intracellular drug delivery systems. In this study, hyaluronic acid (HA)-based pH
      sensitive polymers were designed as multifunctional polymers having not only pH
      sensitivity but also targeting properties to cells expressing CD44, which is
      known as a cancer cell surface marker. Carboxyl group-introduced HA derivatives
      of two types, MGlu-HA and CHex-HA, which have a more hydrophobic side chain
      structure than that of MGlu-HA, were synthesized by reaction with various
      dicarboxylic anhydrides. These polymer-modified liposomes were stable at neutral
      pH, but showed content release under weakly acidic conditions. CHex-HA-modified
      liposomes delivered their contents into CD44-expressing cells more efficiently
      than HA-modified or MGlu-HA-modified liposomes or unmodified liposomes, whereas
      the same liposomes were taken up only slightly by cells expressing CD44 proteins
      less. Competition assay using free HA or other polymers revealed that HA
      derivative-modified liposomes might be recognized by CD44. Therefore, HA
      derivative-modified liposomes are useful as cell-specific intracellular drug
      delivery systems.

PMID- 29183112
TI  - Critical Point Confluence Phenomenon.
AB  - Experimental observation of coexisting isotropic chiral liquids for a single
      molecular substance has motivated creation of a simple lattice model to
      investigate phase transitions in such systems. Specifically, this model permits
      the simultaneous existence of two distinct types of critical points, the familiar
      liquid-vapor case, and a case involving spontaneous chiral symmetry breaking
      within the fluid system. The molecular interactions involved may extend beyond
      nearest neighbor lattice cells. The mean field approximation has been invoked to
      attain explicit results, which include a description of the singular situation
      for which the two critical points undergo confluence in the temperature-density
      plane. In particular, this confluence enhances the chiral symmetry breaking
      phenomenon, leading to a modified critical exponent.

PMID- 29183111
TI  - Remote Activation of a Nanopore for High-Performance Genetic Detection Using a pH
      Taxis-Mimicking Mechanism.
AB  - Aerolysin protein pore has been widely used for sensing peptides and proteins.
      However, only a few groups explored this nanopore for nucleic acids detection.
      The challenge is the extremely low capture efficiency for nucleic acids (>10
      bases), which severely lowers the sensitivity of an aerolysin-based genetic
      biosensor. Here we reported a simple and easy-to-operate approach to
      noncovalently transform aerolysin into a highly nucleic acids-sensitive nanopore.
      Through a remote pH-modulation mechanism, we simply lower the pH on one side of
      the pore, then aerolysin is immediately "activated" and enabled to capture target
      DNA/RNA efficiently from the opposite side of the pore. This mechanism also
      decelerates DNA translocation, a desired property for sequencing and gene
      detection, allowing temporal separation of DNAs in different lengths. This method
      provides insight into the nanopore engineering for biosensing, making aerolysin
      applicable in genetic and epigenetic detections of long nucleic acids.

PMID- 29183113
TI  - Comparison between the Bethe-Salpeter Equation and Configuration Interaction
      Approaches for Solving a Quantum Chemistry Problem: Calculating the Excitation
      Energy for Finite 1D Hubbard Chains.
AB  - We calculate the excitation energies of finite 1D Hubbard chains with a variety
      of different site energies from two perspectives: (i) the physics-based Bethe
      Salpeter equation (BSE) method and (ii) the chemistry-based configuration
      interaction (CI) approach. Results obtained from all methods are compared against
      the exact values for three classes of systems: metallic, impurity-doped, and
      molecular (semiconducting/insulating) systems. While in a previous study we
      showed that the GW method holds comparative advantages versus traditional quantum
      chemistry approaches for calculating the ionization potentials and electron
      affinities across a large range of Hamiltonians, we show now that the BSE method
      outperforms CI approaches only for metallic and semiconducting systems. For
      insulating molecular systems, CI approaches generate better results.

PMID- 29183114
TI  - DNAzyme-Mediated Assays for Amplified Detection of Nucleic Acids and Proteins.

PMID- 29183115
TI  - Bypass of an Abasic Site via the A-Rule by DNA Polymerase of Pseudomonas
      aeruginosa Phage PaP1.
AB  - The abasic site is one the most common DNA lesions formed in cells; it induces a
      severe blockage of DNA replication and is highly mutagenic. We continue to use
      Gp90 exo-, the sole DNA polymerase from Pseudomonas aeruginosa phage PaP1, to
      study DNA replication upon encountering an abasic site lesion. Gp90 exo- can
      incorporate dNTPs opposite the abasic site, but extension past this site is
      extremely slow. Among the four dNTPs, dATP is preferentially incorporated
      opposite the abasic site, consistent with the A-rule. The incorporation is
      independent of the identity of the nucleotide 5' of the abasic site. The
      incorporation of dATP opposite the abasic site occurs by direct incorporation of
      dNTP opposite the abasic site without a -1 frameshift deletion. Extension from an
      A:abasic site pair by Gp90 exo- is slightly unfavorable relative to those from
      other abasic site pairs. Incorporation of dATP opposite the abasic site is
      preferential and shows a biphasic shape, indicating that this incorporation is
      much faster than the subsequent dissociation of the polymerase from DNA. The
      template sequence does not affect the dATP incorporation priority, burst
      amplitude, burst rate, or dATP dissociation constant. Surface plasmon resonance
      shows that the presence of an abasic site in the template weakens the binding
      affinity of Gp90 exo- to DNA in a binary or ternary complex in the presence of
      any one kind of dNTP. This study reveals that Gp90 exo- preferentially inserts A
      opposite an abasic site via the A-rule, like other DNA polymerases (e.g., Pol
      theta, KlenTaq, KF exo-, Pols alpha, delta/PCNA, and Thermococcus litoralis Pol
      Vent (exo-)), providing further insight into DNA replication mediated by P.
      aeruginosa phage PaP1 upon encountering an abasic site lesion.

PMID- 29183116
TI  - Influence of Chain Rigidity and Dielectric Constant on the Glass Transition
      Temperature in Polymerized Ionic Liquids.
AB  - Polymerized ionic liquids (PolyILs) are promising candidates for a wide range of
      technological applications due to their single ion conductivity and good
      mechanical properties. Tuning the glass transition temperature (Tg) in these
      materials constitutes a major strategy to improve room temperature conductivity
      while controlling their mechanical properties. In this work, we show experimental
      and simulation results demonstrating that in these materials Tg does not follow a
      universal scaling behavior with the volume of the structural units Vm (including
      monomer and counterion). Instead, Tg is significantly influenced by the chain
      flexibility and polymer dielectric constant. We propose a simplified empirical
      model that includes the electrostatic interactions and chain flexibility to
      describe Tg in PolyILs. Our model enables design of new functional PolyILs with
      the desired Tg.

PMID- 29183117
TI  - Isothermal Amplification on a Structure-Switchable Symmetric Toehold Dumbbell
      Template: A Strategy Enabling MicroRNA Analysis at the Single-Cell Level with
      Ultrahigh Specificity and Accuracy.
AB  - Accurate analysis of microRNAs (miRNAs) at the single-cell level seriously
      requires analytical methods possessing extremely high sensitivity, specificity
      and precision. By rational engineering of a structure-switchable symmetric
      toehold dumbbell-template (STD-template), we propose a novel isothermal symmetric
      exponential amplification reaction (SEXPAR) method. The sealed and symmetric
      structure of the STD-template allows exponential amplification reaction (EXPAR)
      to occur upon every annealing of target miRNA without loss of amplification
      efficiency. In addition, the rigid and compact structure of the STD-template with
      an appropriate standard free energy ensures SEXPAR only be activated by target
      miRNA. As a result, the SEXPAR method isothermally quantified let-7a down to 0.01
      zmol (6.02 copies per 10 MUL) with an ultrahigh specificity which is efficient
      enough to discriminate one-base-mismatched miRNAs, and a remarkably high
      precision even for the determination of 6.02 copies let-7a (the standard
      deviation was reduced from >60% down to 23%). The dynamic range was also extended
      to 10 orders of magnitude. The method was successfully applied for the
      determination of let-7a in human tissues, sera and even single-cell lysate, with
      obviously better precision than quantitative reverse transcription polymerase
      chain reaction (RT-qPCR) and other EXPAR-based methods. The SEXPAR method may
      serve as a powerful technique for the biological research and biomedical studies
      of miRNAs and other short nucleic acids.

PMID- 29183118
TI  - Aluminum Atom Activation of C-S Bonds: An EPR Study of the Intermediates Formed
      in the Reaction Between Aluminum Atoms and Dialkyl Sulfides.
AB  - The major mononuclear aluminum species obtained in the reaction of aluminum atoms
      with dimethyl sulfide (DMS) and diethyl sulfide (DES), under cryogenic
      conditions, are the C-S insertion products, CH3AlSCH3 and CH3CH2AlSCH2CH3,
      respectively, showing that aluminum atoms can activate C-S bonds. The magnetic
      parameters were extracted from the EPR spectrum. Support for the spectral
      assignment was obtained by repeating the experiments with 13C-labeled dimethyl
      sulfide yielding 13CH3AlS13CH3. DFT calculations using the M06 functional have
      proven to be effective in predicting the isotropic and anisotropic Al hyperfine
      interaction values of the aluminum atom C-S insertion products. In addition, the
      thioalkyl radicals, CH3SCH2* and CH3CH2SCH*CH3 were formed in the aluminum atom
      reaction.

PMID- 29183119
TI  - Encoding Microreactors with Droplet Chains in Microfluidics.
AB  - Droplet-based high throughput biomolecular screening and combinatorial synthesis
      entail a viable indexing strategy to be developed for the identification of each
      microreactor. Here, we propose a novel indexing scheme based on the generation of
      droplet sequences on demand to form unique encoding droplet chains in fluidic
      networks. These codes are represented by multiunit and multilevel droplets
      packages, with each code unit possessing several distinct signal levels,
      potentially allowing large encoding capacity. For proof of concept, we use
      magnetic nanoparticles as the encoding material and a giant magnetoresistance
      (GMR) sensor-based active sorting system supplemented with an optical detector to
      generate and decode the sequence of one exemplar sample droplet reactor and a 4
      unit quaternary magnetic code. The indexing capacity offered by 4-unit multilevel
      codes with this indexing strategy is estimated to exceed 104, which holds great
      promise for large-scale droplet-based screening and synthesis.

PMID- 29183120
TI  - Spectroscopic Investigation of the Primary Reaction Intermediates in the
      Oxidation of Levitated Droplets of Energetic Ionic Liquids.
AB  - The production of the next generation of hypergolic, ionic-liquid-based fuels
      requires an understanding of the reaction mechanisms between the ionic liquid and
      oxidizer. We probed reactions between a levitated droplet of 1-methyl-4-amino
      1,2,4-triazolium dicyanamide ([MAT][DCA]), with and without hydrogen-capped boron
      nanoparticles, and the nitrogen dioxide (NO2) oxidizer. The apparatus exploits an
      ultrasonic levitator enclosed within a pressure-compatible process chamber
      equipped with complementary Raman, ultraviolet-visible, and Fourier-transform
      infrared (FTIR) spectroscopic probes. Vibrational modes were first assigned to
      the FTIR and Raman spectra of droplets levitated in argon. Spectra were
      subsequently collected for pure and boron-doped [MAT][DCA] exposed to nitrogen
      dioxide. By comparison with electronic structure calculations, some of the newly
      formed modes suggest that the N atom of the NO2 molecule bonds to a terminal N on
      the dicyanamide anion yielding [O2N-NCNCN]-. This represents the first
      spectroscopic evidence of a key reaction intermediate in the oxidation of
      levitated ionic liquid droplets.

PMID- 29183121
TI  - Comparison of Internal Standard Approaches for SRM Analysis of Alpha-Synuclein in
      Cerebrospinal Fluid.
AB  - Absolute protein quantification by selected reaction monitoring (SRM, also MRM)
      is an alternative to immunoassays, and the gold standard here is the addition of
      stable-isotope labeled (SIL) proteins (PSAQ). Cerebrospinal fluid (CSF) is the
      preferred source of biomarkers for neurological diseases, and recent improvements
      in mass spectrometry enable the quantification of disease-relevant proteins in
      CSF. We used alpha-synuclein SRM to investigate alternatives to the PSAQ approach
      in human CSF regarding precision and accuracy, including SIL peptides, winged SIL
      (WiSIL) peptides, and quantitative protein epitope signature tags (QPrESTs). All
      approaches yielded precise results in CSF with CV values <15% in several runs for
      all four measured peptides. PSAQ and QPrEST also showed good accuracy (deviation
      <=15%), whereas SIL and WiSIL peptides yielded deviations up to 54% that greatly
      depended on the measured peptide. Total protein concentration in CSF did not
      affect precision and accuracy. Thus, our study indicates that all four approaches
      are suitable for relative quantification of alpha-synuclein in CSF. QPrESTs are a
      valuable alternative to PSAQ in terms of precision and accuracy, although SIL and
      WiSIL peptides can yield accurate results as well when peptides are selected
      consciously.

PMID- 29183122
TI  - Nanoscale Interparticle Distance within Dimers in Solution Measured by Light
      Scattering.
AB  - We demonstrate a novel approach to quantify the interparticle distance in
      colloidal dimers using Mie scattering. The interparticle distance is varied in a
      controlled way by changing the ionic strength of the solution and the magnetic
      attraction between the particles. The measured scaling behavior is interpreted
      using an energy-distance model that includes the repulsive electrostatic and
      attractive magnetic interactions. The center-to-center distances of particles
      with a 525 nm radius can be determined with a root-mean-square accuracy of 12 nm.
      The data show that the center-to-center distance is larger by 83 nm compared to
      perfect spheres. The underlying distance offset can be attributed to repulsion by
      charged protrusions caused by particle surface roughness. The measurement method
      accurately quantifies interparticle distances that can be used to study cluster
      formation and colloid aggregation in complex systems, e.g., in biosensing
      applications.

PMID- 29183123
TI  - Mechanistic Study on Aryl-Exchange Reaction of Diaryl-lambda3-iodane with Aryl
      Iodide.
AB  - Because of its hyper-leaving ability, as well as its strong oxidizing ability,
      diaryl(triflato)-lambda3-iodane transfers one of the aryl groups to iodoarenes
      simply upon gentle heating (>85  degrees C) in nonpolar solvents. We have
      performed an in-depth mechanistic study of this unusual aryl transfer reaction. A
      combination of experimental (product analysis, kinetic study, and substituent
      effects) and density functional theoretical approaches revealed that the reaction
      proceeds through a concerted bimolecular transition state, in which ipso-carbon
      binds loosely to both iodine centers. We also evaluated electronic effects on the
      thermodynamic stability of diaryl-lambda3-iodanes.

PMID- 29183125
TI  - Quantifying Microsecond Transition Times Using Fluorescence Lifetime Correlation
      Spectroscopy.
AB  - Many complex luminescent emitters such as fluorescent proteins exhibit multiple
      emitting states that result in rapid fluctuations of their excited-state
      lifetime. Here, we apply fluorescence lifetime correlation spectroscopy (FLCS) to
      resolve the photophysical state dynamics of the prototypical fluorescence protein
      enhanced green fluorescent protein (EGFP). We quantify the microsecond transition
      rates between its two fluorescent states, which have otherwise highly overlapping
      emission spectra. We relate these transitions to a room-temperature angstrom
      scale rotational isomerism of an amino acid next to its fluorescent center. With
      this study, we demonstrate the power of FLCS for studying the rapid transition
      dynamics of a broad range of light-emitting systems with complex multistate
      photophysics, which cannot be easily done by other methods.

PMID- 29183126
TI  - Microfluidic Module for Real-Time Generation of Complex Multimolecule Temporal
      Concentration Profiles.
AB  - We designed a microfluidic module that generates complex and dynamic
      concentration profiles of multiple molecules over a large concentration range
      using pulse-width modulation (PWM). Our PWM module can combine up to six
      different inputs and select among three downstream mixing channels, as required
      by the application. The module can produce concentrations with a dynamic range of
      three decades. We created complex, temporal concentration profiles of two
      molecules, with each concentration independently controllable, and show that the
      PWM module can execute rapid concentration changes as well as long-time scale
      pharmacokinetic profiles. Concentration profiles were generated for molecules
      with molecular weights ranging from 560 Da to 150 kDa. Our PWM module produces
      robust and precise concentration profiles under a variety of operating
      conditions, making it ideal for integration with existing microfluidic devices
      for advanced cell and pharmacokinetic studies.

PMID- 29183124
TI  - New Triterpenoid Saponins from Green Vegetable Soya Beans and Their Anti
      Inflammatory Activities.
AB  - Ten compounds were isolated and identified from green vegetable soya beans, of
      which five are new triterpenoid saponins (1-5) and five are known compounds (6
      10). The chemical structures of the five triterpenoid saponins (1-5) were
      elucidated to be 3beta,24-dihydroxy-22beta,30-epoxy-30-oxoolean-12-en 3-O-alpha-l
      rhamnopyranosyl-(1 -> 2)-beta-d-xylopyranosyl-(1 -> 2)-beta-d
      glucuronopyranoside, 1; 3beta,24-dihydroxy-22beta,30-epoxy-30-oxoolean-12-en 3-O
      alpha-l-rhamnopyranosyl-(1 -> 2)-beta-d-(3"-O-formyl)-galactopyranosyl-(1 -> 2)
      beta-d-glucuronopyranoside, 2; 22-keto-3beta,24-dihydroxy oleanane-12-ene 3-O
      alpha-l-rhamnopyranosyl-(1 -> 2)-beta-d-(3"-O-formyl)-galactopyranosyl-(1 -> 2)
      beta-d-glucuronopyranoside, 3; 3beta,22beta,24-trihydroxy oxyolean-18(19)-ene-29
      acid 3-O-alpha-l-rhamnopyranosyl-(1 -> 2)-beta-d-galactopyranosyl-(1 -> 2)-beta-d
      glucuronopyranoside, 4; and punicanolic acid 3-O-alpha-l-rhamnopyranosyl-(1 -> 2)
      beta-d-galactopyranosyl-(1 -> 2)-beta-d-glucuronopyranoside, 5 from the
      spectroscopic data (IR, GTC/FID, HR-ESI-MS, and 1D and 2D NMR). The nitric oxide
      release inhibitions of compounds 1-10 in LPS-stimulated RAW264.7 cells were
      evaluated, and the data suggested that compounds 1, 2, and 5 might possess
      moderate anti-inflammatory activities, with IC50 values of 18.8, 16.1, and 13.2
      MUM, respectively.

PMID- 29183127
TI  - First Chemosensor for Selective Detection and Quantification of L-4
      Hydroxyproline in Collagen and Other Bio Samples.
AB  - Amino pyridine-based rhodamine conjugate (APR) has been developed as a first
      chemosensor for selective detection and quantification of L-4-Hydroxyproline
      (Hyp). The "turn-on" fluorescence property of the chemosensor makes it unique for
      easy estimation of Hyp in collagen and biological samples.

PMID- 29183129
TI  - Synthesis of 4,5-Diazaspiro[2.3]hexanes and 1,2-Diazaspiro[3.3]heptanes as
      Hexahydropyridazine Analogues.
AB  - 4,5-Diazaspiro[2.3]hexanes are made by dihalocarbene addition across the
      exocyclic double bond of readily accessible 3-alkylidene-1,2-diazetidines. Using
      difluorocarbene, generated from TMSCF3/NaI, these spirocycles were produced in
      yields up to 97% by stereospecific addition across the alkene. Lower yields (up
      to 64%) were observed using more reactive dichlorocarbene, due to competitive
      insertion of the carbene into the N-N bond. Larger 1,2-diazaspiro[3.3]heptanes
      are produced by [2 + 2] cycloaddition of 3-alkylidene-1,2-diazetidines with
      tetracyanoethylene (TCNE) in up to 99% yield.

PMID- 29183128
TI  - Performance Evaluation of the Q Exactive HF-X for Shotgun Proteomics.
AB  - Progress in proteomics is mainly driven by advances in mass spectrometric (MS)
      technologies. Here we benchmarked the performance of the latest MS instrument in
      the benchtop Orbitrap series, the Q Exactive HF-X, against its predecessor for
      proteomics applications. A new peak-picking algorithm, a brighter ion source, and
      optimized ion transfers enable productive MS/MS acquisition above 40 Hz at 7500
      resolution. The hardware and software improvements collectively resulted in
      improved peptide and protein identifications across all comparable conditions,
      with an increase of up to 50 percent at short LC-MS gradients, yielding
      identification rates of more than 1000 unique peptides per minute. Alternatively,
      the Q Exactive HF-X is capable of achieving the same proteome coverage as its
      predecessor in approximately half the gradient time or at 10-fold lower sample
      loads. The Q Exactive HF-X also enables rapid phosphoproteomics with routine
      analysis of more than 5000 phosphopeptides with short single-shot 15 min LC-MS/MS
      measurements, or 16 700 phosphopeptides quantified across ten conditions in six
      gradient hours using TMT10-plex and offline peptide fractionation. Finally,
      exciting perspectives for data-independent acquisition are highlighted with
      reproducible identification of 55 000 unique peptides covering 5900 proteins in
      half an hour of MS analysis.

PMID- 29183130
TI  - A Theoretical Study of HF-CH3Cl and (HF)2-CH3Cl Complexes.
AB  - The equilibrium geometries, relative stabilities, and vibrational properties
      (frequencies and intensities) of the HF-CH3Cl (1:1) and (HF)2-CH3Cl (1:2)
      complexes were reinvestigated at the MP2/Aug-cc-pVTZ level. The results are
      discussed in light of the results obtained in solid argon matrices by L. Andrews
      and co-workers and related to the bonding analysis. The stability and cooperative
      effects in the hydrogen bonding of the (HF)2-CH3Cl complex in its cyclic form are
      outlined.

PMID- 29183133
TI  - Distribution of Human Papillomavirus Genotype in Anal Condyloma Acuminatum Among
      Japanese Men: The Higher Prevalence of High Risk Human Papillomavirus in Men Who
      Have Sex with Men with HIV Infection.
AB  - Human papillomavirus (HPV) infection is known to cause anal condyloma acuminatum
      (CA) and squamous cell carcinoma. Men who have sex with men (MSM) with HIV
      infection are frequently co-infected with HPV, especially high risk HPV (HR-HPV)
      that causes anal squamous cell carcinoma. However, there are few reports of HPV
      genotype studies in anal lesion of Japanese men. We tried to estimate the
      distribution of HPV genotypes in anal CA tissue specimens from the Japanese men
      to elucidate the risk of anal cancer. A total of 62 patients who had anal CA
      surgically excised were enrolled. They included 27 HIV-positive MSM, 18 HIV
      negative MSM, 1 HIV-positive man who have sex with women (MSW), and 16 HIV
      negative MSW. HPV genotypes in anal CA tissue were determined by the polymerase
      chain reaction technique with reverse line blot hybridization. HR-HPV was
      detected in 45.2% of the CA tissue specimens and high grade squamous
      intraepithelial lesion (HSIL) was observed in 15.3%. Moreover, the prevalence of
      HR-HPV in the HIV-positive MSM (70.4%) was higher than the HIV-negative MSM
      (33.3%, p = .0311) or the HIV-negative MSW (18.8%, p = .0016). The conditional
      logistic regression analysis suggested HIV positivity as the primary risk factor
      for the HR-HPV infection in CA. In addition, HSIL was detected in higher
      frequency in CA tissues from HIV-positive MSM (25.9%) than HIV-negative MSW
      (0.0%, p = .0346). HR-HPV and HSIL were frequently detected in anal CA tissues
      from Japanese MSM patients with HIV infection, suggesting the necessity of
      surveillance for this population.

PMID- 29183134
TI  - In Vitro Transduction and Target-Mutagenesis Efficiency of HIV-1 pol Gene
      Targeting ZFN and CRISPR/Cas9 Delivered by Various Plasmids and/or Vectors:
      Toward an HIV Cure.
AB  - Efficiency of artificial restriction enzymes toward curing HIV has only been
      separately examined, using differing delivery vehicles. We compared the in vitro
      transduction and target-mutagenesis efficiency of consortium plasmid and
      adenoviral vector delivered HIV-1 pol gene targeting zinc finger nuclease (ZFN)
      with CRISPR/Cas, Custom-ZFN, CRISPR-Cas-9, and plasmids and vectors
      (murCTSD_pZFN, pGS-U-gRNA, pCMV-Cas-D01A, Ad5-RGD); cell lines (TZM-bl and ACH
      2/J-Lat cells); and the latency reversing agents prostratin, suberoylanilide
      hydroxamic acid, and phorbol myristate acetate. Cell lines were grown in either
      Dulbecco's modified Eagle's medium or Roswell Park Memorial Institute with the
      antibiotics kanamycin, zeocin, and efavirenz. Efficiency was assayed by
      GFP/luciferase activity and/or validated by yeast MEL1 reporter assay, CEL1
      restriction fragment assay, and quantitative reverse transcriptase-polymerase
      chain reaction (qRT-PCR). Ad5-RGD vectors had better transduction efficiency than
      murCTSD and pGS-U-gRNA/pCMV-Cas-D01A plasmids. CRISPR/Cas9 exhibited better
      target-mutagenesis efficiency relative to ZFN (delivered by either plasmid or Ad5
      vector) based on gel electrophoresis of pol gene amplicons within ACH-2 and J-Lat
      cells. Ad-5-RGD vectors enhanced target mutagenesis of ZFN, relative to
      murCTSD_pZFN plasmids, to levels of CRISPR/Cas9 plasmids. Similar reduction of
      luciferase activity among TZM-bl treated with Ad5-ZFN vectors relative to
      CRISPR/Cas-9 and murCTSD_pZFN plasmids was observed on challenge with HIV-1. qRT
      PCR of HIV-1 pol gene transcripts affirmed that Ad5 (RGD) vectors enhanced target
      mutagenesis of ZFN. Whereas CRISPR/Cas-9 may possess inherent superior target
      mutagenesis efficiency; the efficiency of ZFN (off-target toxicity withstanding)
      can be enhanced by altering delivery vehicle from plasmid to Ad5 (RGD) vectors.

PMID- 29183131
TI  - Resolving the NFkappaB Heterodimer Binding Paradox: Strain and Frustration Guide
      the Binding of Dimeric Transcription Factors.
AB  - Many eukaryotic transcription factors function after forming oligomers. The
      choice of protein partners is a nonrandom event that has distinct functional
      consequences for gene regulation. In the present work we examine three dimers of
      transcription factors in the NFkappaB family: p50p50, p50p65, and p65p65. The
      NFkappaB dimers bind to a myriad of genomic sites and switch the targeted genes
      on or off with precision. The p65p50 heterodimer of NFkappaB is the strongest DNA
      binder, and its unbinding is controlled kinetically by molecular stripping from
      the DNA induced by IkappaB. In contrast, the homodimeric forms of NFkappaB,
      p50p50 and p65p65, bind DNA with significantly less affinity, which places the
      DNA residence of the homodimers under thermodynamic rather than kinetic control.
      It seems paradoxical that the heterodimer should bind more strongly than either
      of the symmetric homodimers since DNA is a nearly symmetric target. Using a
      variety of energy landscape analysis tools, here we uncover the features in the
      molecular architecture of NFkappaB dimers that are responsible for these
      drastically different binding free energies. We show that frustration in the
      heterodimer interface gives the heterodimer greater conformational plasticity,
      allowing the heterodimer to better accommodate the DNA. We also show how the
      elastic energy and mechanical strain in NFkappaB dimers can be found by
      extracting the principal components of the fluctuations in Cartesian coordinates
      as well as fluctuations in the space of physical contacts, which are sampled via
      simulations with a predictive energy landscape Hamiltonian. These energetic
      contributions determine the specific detailed mechanisms of binding and stripping
      for both homo- and heterodimers.

PMID- 29183135
TI  - [A rare case of gastric outlet syndrome: internal incarceration after removal of
      gastric banding].
AB  - The laparoscopically administrated adjustable gastric banding used to be widely
      practiced as treatment of extreme obesity. As lots of complaints and
      complications arose sooner or later after this procedure, they had to be removed
      quite often. Half year after such a removal we observed a 37-year-old female
      patient with complete gastric outlet obstruction. The patient was operated and
      cured completely. The cause of gastric obstruction was an internal incarceration
      of the pyloric region between the plication made at the time of the ring removal
      and the gastric body. We found no similar case of gastric outlet obstruction in
      the corresponding literature.

PMID- 29183136
TI  - [Laparoscopic cecal wedge resection].
AB  - INTRODUCTION: Several indications of cecal wedge resection can be found in the
      literature, but the most common ones are acute appendicitis, appendiceal mucocele
      and selected cecal polyps. PURPOSE: We summarize the indications, review the
      results of laparoscopic cecal wedge resections carried out in our department from
      01.01.2010 till 31.12.2016. A case report is presented when cecal resection was
      carried out for a cecal polyp. PATIENTS: Between 01.01.2010 and 31.12.2016, 56
      patients underwent a laparoscopic cecal wedge resection. The mean age was 42
      years (14-83), 28 males and 28 females. In 46 cases, the indication was
      complicated acute appendicitis, in 6 cases appendiceal mucocele, in the case of
      four patients endoscopically unresectable benign cecal polyps. RESULTS: The
      average operating time was 65 minutes. For the procedure we used two 10 mm and
      one 5 mm port, the resection was performed by using 45 or 60 mm laparoscopic
      stapler. In 57.1% of the reviewed cases, abdominal drainage was applied.
      Conversion was necessary in the case of 3 patients (5.4%), once due to bleeding,
      twice due to technical problems. Surgical complications occured in 4 patients
      (7.1%), all of them from the complicated appendicitis group: one of grade I by
      Clavien-Dindo, 3 of grade III. The reoperation rate was 5.4% (3 patients):
      reoperation was accounted for an abdominal wall phlegmon, a pericecal abscess,
      and once the suspicion of abdominal abscess which was not verified. Perioperative
      death did not occur.

PMID- 29183137
TI  - [Thoracodorsal artery perforator fasciocutaneous flap in the treatment of chronic
      hidradenitis suppurativa of axilla].
AB  - BACKGROUND: The only definitive treatment of chronic axillar hidradenitis
      suppurativa (HS) that prevents relapses is 'in toto' excision of the infected
      glandular tissue. This way a deficiency emerges, which needs to be restored.
      Reconstruction with split skin graft (SSG) is a most common way of recovery, but
      thoracodorsal artery perforator (TDAP) fasciocutneous flap delivers better
      functional and aesthetic results. METHOD: Between May 2014 and July 2016, 14
      patients underwent reconstructive surgery after excision of axillary HS, 2 of
      them had bilateral lesion. In 15 cases TDAP was used, in 1 case we used
      thoracodorsal artery capillar perforator flap (TAPcp). RESULTS: In all but 2
      cases 1 dominant perforator was found. 1 flap had 2 dominant perforators and 1
      flap was supplied by capillary perforators. Size of the flaps spread between 6 *
      8 and 10 * 15 cm. 15 reconstructions were successful, 1 flap necrotised because
      of the lack of compliance of the patient. CONCLUSION: As a result of the
      glandular tissue excision carried out because of a chronic HS, a deficiency
      emerges. TDAP flap is an ideal solution for surgical reconstruction of axillar
      deficiencies, and a great alternative to SSG.

PMID- 29183139
TI  - ?

PMID- 29183140
TI  - ?

PMID- 29183138
TI  - [Experimental model for cardiogenic shock with pericardial tamponade].
AB  - INTRODUCTION: Pericardial tamponade (PT) is a life-threatening condition, with
      low cardiac output. The hemodynamic consequences of PT can severely affect the
      circulation of all tissues, including the microcirculation of the kidneys and the
      intestinal mucosa. Our aim was to develop a hemodynamically stable and
      controllable large animal model of PT to study the consequences of cardiogenic
      shock. METHODS: Two groups of anesthetized vietnamese minipigs (n = 6, both
      groups) were used. Following laparotomy, a cannula was fixed into the pericardium
      through the diaphragm without thoracotomy. A sham-operated group served as
      control, in the second group 60-min PT was induced by intrapericardial injection
      of heparinised own blood. Throughout PT and 180-min reperfusion,
      macrohemodynamics, renal circulation and mesenteric macro- and microcirculation
      were monitored. Myeloperoxidase (MPO) activity was measured and in vivo histology
      was performed by confocal laser scanning endomicroscopy. RESULTS: The PT
      increased central venous pressure, heart rate and decreased mean arterial
      pressure, mesenteric flow (from 355.5 +/- 112.4 vs 182.0 +/- 59.1 ml/min) and
      renal arterial flow (from 159.63 +/- 50.7 vs 35.902 +/- 27.9 ml/min) and the
      microcirculation of the ileum. Elevated MPO activity (3.66 +/- 1.6 vs 7.01 +/-
      1.44 mU/mg protein) and injury of the ileal mucosa were present also. SUMMARY:
      The reproducible large animal model is suitable for clinically relevant
      investigations of the hemodynamic and biochemical consequences of PT.

PMID- 29183141
TI  - ?

PMID- 29183142
TI  - ?

PMID- 29183143
TI  - [Letter to the editor].

PMID- 29183144
TI  - [News of the Society].

PMID- 29183145
TI  - Emerging drugs for the treatment of gastrointestinal stromal tumour.
AB  - INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have transformed the treatment
      landscape for patients with gastrointestinal stromal tumors (GIST).
      Unfortunately, resistance to the currently approved TKIs poses a huge challenge,
      and patients are in need of additional therapeutic options. Fortunately, many
      novel therapeutic approaches are being tested in treatment of GIST to overcome
      resistance to the approved TKIs Areas covered: We performed an extensive
      literature (PUBMED) search to identify emerging drugs being tested in treatment
      of GIST in early phase clinical trials. We discuss recent ongoing research and
      emerging novel inhibitors of KIT and PDGFRA receptors, inhibitors in downstream
      signaling pathways (mTOR and PIK3 inhibitors), inhibitors of other potential
      targets including ETV1/MEK, MET, FGFR, IGF1R, histone deacetylase inhibitors,
      heat shock protein 90 inhibitors, cyclin-dependent kinase inhibitors and immune
      checkpoint inhibitors in treatment of GIST Expert opinion: Multiple agents are
      under evaluation; those that benefit GIST patients with imatinib resistant
      mutations, or those with benefit in patients refractory to approved agents are
      most likely to be developed in this disease. The role of immunotherapy for GIST
      is still investigational.

PMID- 29183146
TI  - Improving Rates of Screening for Anemia in Infancy.
AB  - In 2010, the American Academy of Pediatrics recommended universal screening for
      anemia at approximately 1 year of age. This quality improvement study sought to
      improve anemia screening in an ambulatory setting. In a large university-based
      setting, a best practice alert (BPA) was placed within the electronic health
      record. The primary outcome was overall screening rate in ambulatory family
      medicine (DFM) and pediatrics (PEDS) clinics. From 2545 pre-BPA clinic visits
      over a 12-month period, the screening rate was 48.2%. Among 2186 post-BPA clinic
      visits over an 8-month period, the screening rate improved to 72.7%, P < .0001.
      Follow-up over a second 7-month period demonstrated sustained improvements
      (70.8%) but was not higher after educational sessions between the periods.
      Screening rates were higher in PEDS than DFM at each time point; P < .0001. This
      technology-based intervention increased and maintained higher screening rates for
      anemia at 1 year, with higher rates in PEDS.

PMID- 29183147
TI  - Development and optimization of sulforaphane-loaded nanostructured lipid carriers
      by the Box-Behnken design for improved oral efficacy against cancer: in vitro, ex
      vivo and in vivo assessments.
AB  - In the present study, sulforaphane (SFN)-loaded nanostructured lipid carriers
      (NLC) were developed and optimized for improved oral efficacy against cancer. The
      SFN-loaded NLC formulation was developed by melt emulsification ultrasonication
      technique and optimized by Box-Behnken statistical design. The optimized SFN
      loaded NLC formulation composed of precirol(r) ATO 5 (solid lipid) and vitamin E
      (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and Tween 80 (1%) as
      surfactant. The mean particle size, polydispersity index, zeta potential,
      entrapment efficiency (%) and drug loading (%) of optimized SFN-loaded NLC
      formulation was observed to be 145.38 +/- 4.46 nm, 0.181 +/- 0.023, -25.12 +/-
      2.36 mV, 84.94 +/- 3.82% and 14.82 +/- 3.46%, respectively. In vitro drug release
      studies showed that the release of SFN from optimized NLC formulation was
      significantly higher (86.52 +/- 5.48%) compared to SFN suspension (38.47 +/-
      5.52%) up to 24 h. Ex vivo gut permeation studies revealed a very good
      enhancement in permeation of drug present in the NLC compared to plain SFN
      solution and were further confirmed by CLSM. MTT assay in different cancer cell
      lines showed that the optimized SFN-loaded NLC formulation exhibited
      significantly improved (p < .05) cytotoxicity compared to free SFN solution. SFN
      loaded NLC formulation showed significantly improved antioxidant activity
      compared to free SFN solution. Furthermore, pharmacokinetic study on albino
      Wistar rats showed 5.04-fold increase in relative oral bioavailability with NLC
      (p < .05) compared to SFN suspension. Therefore, NLC represents a great potential
      for improved efficacy of SFN after oral administration.

PMID- 29183148
TI  - Humanized mouse models infected with human Plasmodium species for antimalarial
      drug discovery.
AB  - INTRODUCTION: Efforts on malaria drug discovery are expected to increase in the
      coming years to achieve malaria eradication. Owing to the increasing number of
      new potential candidates together with the actual limitations of the primate
      models, humanized mouse models infected with human Plasmodium spp. (HmHP) now
      appear as an alternative to the primate model. Areas covered: The authors review
      the progress obtained in the HmHP in the last two decades, with a special
      emphasis of their input on the drug discovery pathway. The authors discuss the
      methodologies and strategies used in these models to obtain an accurate
      assessment of the compound activity and a reliable prediction of the human
      efficacious regimen. Expert opinion: Research efforts have led us to an era in
      which HmHP can successfully be infected with P. falciparum, P vivax and P. ovale.
      Furthermore, it is now a reality that the complete human cycle of P. falciparum
      can be obtained in HmHP. The HmHP has shown a real input mainly in the
      preclinical evaluation of new compounds against the erythrocytic stages of P.
      falciparum. However, further technical improvements are needed before HmHP may
      replace the primate model.

PMID- 29183149
TI  - A Department of Medicine Infrastructure for Patient Safety and Clinical Quality
      Improvement.
AB  - Payers, providers, and patients increasingly recognize the importance of quality
      and safety in health care. Academic Departments of Medicine can advance quality
      and safety given the large populations they serve and the broad spectrum of
      diseases they treat. However, there are only few detailed examples of how quality
      and safety can be organized. This article describes a practical model at The
      Johns Hopkins Hospital Department of Medicine and details its structure and
      operation within a large academic health system. It is based on a fractal model
      that integrates multiple smaller units similar in structure (composition of
      faculty/staff), process (use of similar tools), and approach (using a common
      framework to address issues). This organization stresses local, multidisciplinary
      leadership, facilitates horizontal connections for peer learning, and maintains
      vertical connections for broader accountability.

PMID- 29183150
TI  - Effect of Agave americana L. on the human, and Aspergillus oryzae S2 alpha
      amylase inhibitions.
AB  - Among phenolic compounds, Agave americana L. extract contained puerarin (38.4%)
      and p-coumaric acid (12.29%) (pCa). From the Lineweaver-Burk plots, pCa and
      puerarin demonstrated a competitive and a non competitive inhibitions towards
      human alpha-amylase activity, respectively. PCa exhibited a higher human
      inhibitory activity with an IC50 of 98.8 MUM which was about 2.3 times than
      acarbose. Puerarin (IC50 = 3.87 MUM) and pCa (IC50 = 10.16 MUM) also showed an
      excellent inhibition for Aspergillus oryzae S2 alpha-amylase activity. The
      inhibitions of the described biocatalysts compounds towards both amylases were
      significantly decreased when they were pre-incubated with starch. The binding
      modes of these compounds were evaluated in silico. The binding efficiency order
      of these molecules in terms of polar contact numbers for both enzymes was in
      agreement with the in vitro studies. These findings provided a rational reason to
      establish the isolated compounds capability as therapeutic target for
      hyperglycaemia modulation and antifungal therapy.

PMID- 29183151
TI  - Real-time symptom reporting during elective intracranial pressure monitoring
      using an interactive handset.
AB  - BACKGROUND: Determining whether symptoms are related to abnormal intracranial
      pressure (ICP) may prove challenging in some cases. We evaluated the utility of
      an in-house designed interactive handset which allows the real-time recording of
      symptoms during ICP monitoring. METHODS: Adult patients undergoing elective
      continuous ICP monitoring using the device to investigate symptoms between
      November 2013 and June 2015 were included in this retrospective observational
      cohort study. The device allowed the following symptoms to be recorded: mild,
      moderate and severe headache, visual disturbance and nausea. The corresponding
      ICP and ICP trend were also recorded. RESULTS: Twenty seven patients underwent 29
      episodes of ICP monitoring, reporting 383 symptoms (mild 18%, moderate 39%,
      severe 20% headaches, visual disturbance 15% and nausea 8%) over a median period
      of 48 hours (IQR 12). The median number of symptoms reported during each episode
      was 11 (IQR 11). The mean ICP associated with a symptom episode was 7mmHg (Range 
      10 to 45). Mild, moderate and severe headache complaints were associated with
      mean ICPs of 5 (-9 to 26), 6 (-10 to 35) and 14 (-10 to 45) mmHg respectively.
      The majority of complaints (68%) were reported during instances of normal ICP.
      Following monitoring, non-operative management was employed on 21 occasions (72%)
      including valve pressure adjustment on two occasions whilst surgical intervention
      was required on eight occasions (28%; two surgeries for under-drainage and six
      for over-drainage). CONCLUSIONS: The device allows the clinician to accurately
      match a patient's symptoms with ICP to facilitate management decisions. In most
      instances, symptoms did not closely correlate with an abnormal ICP. By automating
      and standardising the collection of symptom data, this device may serve as an
      efficient adjunct when investigating patients with complex hydrocephalus.

PMID- 29183153
TI  - Neurosurgery self-assessment: questions and answers.

PMID- 29183152
TI  - Marathon running increases circulating endothelial- and thrombocyte-derived
      microparticles.
AB  - Background Acute vascular effects of high intensity physical activity are
      incompletely characterized. Circulating microparticles are cellular markers for
      vascular activation and damage. Methods Microparticles were analysed in 99
      marathon runners (49 +/- 6 years, 22% female) of the prospective Berlin Beat of
      Running study. Blood samples were taken within three days before, immediately
      after and within two days after the marathon run. Endothelial-derived
      microparticles were labelled with CD144, CD31 and CD62E, platelet-derived
      microparticles with CD62P and CD42b, leukocyte-derived microparticles with CD45
      and monocyte-derived microparticles with CD14. Results Marathon running induced
      leukocytosis (5.9 +/- 0.1 to 14.8 +/- 0.3 109/l, p < 0.0001) and increased
      platelet counts (239 +/- 4.6 to 281 +/- 5.9 109/l, p < 0.0001) immediately after
      the marathon. Blood monocytes increased and lymphocytes decreased after the run (
      p < 0.0001). Endothelial-derived microparticles were acutely increased ( p =
      0.008) due to a 23% increase of apoptotic endothelial-derived microparticles ( p
      = 0.007) and returned to baseline within two days after the marathon. Thrombocyte
      derived microparticles acutely increased by 38% accompanied by an increase in
      activated and apoptotic thrombocyte-derived microparticles ( p <= 0.0001) each.
      Both monocyte- and leukocyte-derived microparticles were decreased immediately
      after marathon run ( p < 0.0001) and remained below baseline until day 2.
      Troponin T increased from 12 to 32 ng/l ( p < 0.0001) immediately after the run
      and returned to baseline after two days. Conclusion Circulating apoptotic
      endothelial- and thrombocyte-derived microparticles increased after marathon
      running consistent with an acute pro-thrombotic and pro-inflammatory state.
      Exercise-induced vascular damage reflected by microparticles could indicate
      potential mechanisms of post-exertional cardiovascular complications. Further
      studies are warranted to investigate microparticles as markers to identify
      individuals prone to such complications.

PMID- 29183154
TI  - Preparation and evaluation of wet-milled usnic acid nanocrystal suspension for
      better bioaffinity.
AB  - OBJECTIVE: To prepare a new nanosystem of usnic acid (UA) with higher solid
      content and higher bioavailability. METHODS: Usnic acid nanocrystal suspensions
      were prepared by the wet milling method, and then the particle size distributions
      and zeta potential were determined with the Nano ZS90 laser diffraction particle
      size analyzer. The particles morphology of UA-NCS were observed by scanning
      electron microscopy method. In addition, solubility and dissolution of UA-NCS in
      water and phosphate buffer solution were determined in vitro, analyzed by the
      HPLC method, and then the cellular uptake and pharmacokinetic were carried out on
      the Caco-2 cells and rats, analyzed by the UPLC-MS/MS method. RESULTS: Particle
      size distributions and zeta potential of the UA nanocrystal suspension were 268.7
      +/- 4.0 nm and -23.1 +/- 0.7 mV, respectively. About the dissolution rate of UA,
      nanosuspension were significantly faster and higher than common suspension in
      water and phosphate buffer. And in cellular uptake experiments, the ratio of the
      maximum amount of drug in unit protein of UA nanosuspension to common suspension
      was 2.8 times. In rats, oral absorption of nanocrystal UA were superior to the
      ordinary groups, with the 348% of the maximum concentration and 181% of the AUC
      after the same dosage administration. CONCLUSION: The wet-milling technique was
      suitable for the preparation of UA nanocrystal suspension, and a new nanosystem
      of UA with higher solid content and higher bioavailability was achieved.

PMID- 29183155
TI  - Arterial stiffness, plasma atherogenic index and soluble cell adhesion molecules
      in healthy young adults with reduced physical activity.
AB  - OBJECTIVE: To examine some anthropometric parameters, arterial stiffness, lipid
      profile, and soluble adhesion molecules in young adults with reduced physical
      activity. MATERIAL AND METHODS: The study is carried on 54 healthy young adults
      aged 20.97 +/- 2.04 years. Two groups: 23 with reduced physical activity (INAC)
      and 31 with optimal physical activity (AC). Body mass index (BMI), basal
      metabolic rate (BMR), central aortic systolic blood pressure (CSBP, mmHg), plasma
      atherogenic index (AIP), and serum soluble cell adhesion molecules (sICAM-1,
      sVCAM-1) are followed up. RESULTS: CSBP [115.56 +/- 10.22 vs. 105.13 +/- 9.88*],
      AIP [-0.04 +/- 0.18 vs. -0.08 +/- 0.08**] and sICAM-1 [362.5 +/- 49.95 vs. 281.75
      +/- 80.39**] are significantly higher, and BMR [1431 +/- 297.9 vs. 1674.6 +/-
      365.57*] is significantly lower in the physically inactive young healthy adults.
      CONCLUSIONS: CSBP, AIP, and sICAM-1 are higher in young adults with reduced
      physical activity. This plays substantial role in the acceleration of atherogenic
      process and in long-term perspective could promote cardiovascular diseases.

PMID- 29183156
TI  - A bioactive new protostane-type triterpenoid from Alisma plantago-aquatica subsp.
      orientale (Sam.) Sam.
AB  - A new protostane-type triterpenoid, 5beta,29-dihydroxy alisol A (1) was isolated
      from Alisma plantago-aquatica subsp. orientale (Sam.) Sam. as well as 12
      deoxyphorbol-13alpha-pentadecanoate (2). We first report the presence of compound
      2 in the genus Alisma. Their structures were established on the basis of 1D and
      2D NMR, and HRESIMS spectroscopic analyses. All the isolated compounds were
      assayed for their inhibitory effects against human carboxylesterase 2 (HCE-2).
      Compounds 1 and 2 displayed inhibitory activities against HCE-2 with IC50 values
      of 29.2 and 4.6 MUM, respectively. The interaction mechanisms of HCE-2 with
      compounds 1 and 2 were investigated by molecular docking, respectively.

PMID- 29183157
TI  - Severe Hypoglycemia in Adults With Type 1 Diabetes After Switching to Insulin
      Degludec.

PMID- 29183158
TI  - Critical Roles of Glutaredoxin in Brain Cells-Implications for Parkinson's
      Disease.
AB  - SIGNIFICANCE: Glutaredoxin (Grx)1, an evolutionarily conserved and ubiquitous
      enzyme, regulates redox signal transduction and protein redox homeostasis by
      catalyzing reversible S-glutathionylation. Grx1 plays different roles in
      different cell types. In Parkinson's disease (PD), Grx1 regulates apoptosis
      signaling in dopaminergic neurons, so that loss of Grx1 leads to increased cell
      death; in microglial cells, Grx1 regulates proinflammatory signaling, so that
      upregulation of Grx1 promotes cytokine production. Here we examine the regulatory
      roles of Grx1 in PD with a view toward therapeutic innovation. Recent Advances:
      In postmortem midbrain PD samples, Grx1 was decreased relative to controls,
      specifically within dopaminergic neurons. In Caenorhabditis elegans models of PD,
      loss of the Grx1 homologue led to exacerbation of the neurodegenerative
      phenotype. This effect was partially relieved by overexpression of
      neuroprotective DJ-1, consistent with regulation of DJ-1 content by Grx1.
      Increased GLRX copy number in PD patients was associated with earlier PD onset;
      and Grx1 levels correlated with levels of proinflammatory tumor necrosis factor
      alpha in mouse and human brain samples. In vitro studies showed Grx1 to be
      upregulated on proinflammatory activation of microglia. Direct overexpression of
      Grx1 increased microglial activation; silencing Grx1 diminished activation. Grx1
      upregulation in microglia corresponded to increased neuronal cell death in
      coculture. Overall, these studies identify competing roles of Grx1 in PD
      etiology. CRITICAL ISSUES: The dilemma regarding Grx1 as a PD therapeutic target
      is whether to stimulate its upregulation for neuroprotection or inhibit its
      proinflammatory activity. FUTURE DIRECTIONS: Further investigation is needed to
      understand the preponderant role of Grx1 regarding dopaminergic neuronal
      survival. Antioxid. Redox Signal. 00, 000-000.

PMID- 29183159
TI  - Cytotoxicity of new secondary metabolites, fatty acids and tocols composition of
      seeds of Ducrosia anethifolia (DC.) Boiss.
AB  - Two new monoterpene Ducrosin A (1) and sesquiterpene Ducrosin B (2) were isolated
      along with three known compounds, stigmasterol (3) and two furanocoumarins (4 and
      5), from the dichloromethane extract of the seeds of Ducrosia anethifolia (DC.)
      Boiss. Their structures were determined using extensive 1D and 2D NMR, (ES)-HRMS
      and IR spectroscopic analyses and by comparison with literature data. Gas
      chromatography analysis of the fatty acids (FAs) of D. anethifolia seed oils
      (DAOs) showed high percentages of elaidic acid (C18:1 Delta9t) 65% and oleic acid
      (C18:1 Delta9c) 15%. The total tocopherol (tocols) content in DAOs was found to
      be 164 mg/100 g. The cytotoxic effect of the isolates was also evaluated using
      the MTT assay against the HCT-116 and SKOV-3 cell lines. The results showed that
      compound 2 was the most cytotoxic agent followed by compounds 1 and 4, which has
      an epoxide moiety that most likely contributes to its activity.

PMID- 29183160
TI  - Daily spirometry in an acute exacerbation of adult cystic fibrosis patients.
AB  - To help answer the question of length of intravenous antibiotics during an acute
      exacerbation of cystic fibrosis (CF), we had subjects to follow daily home
      spirometry while on intravenous antibiotics. CF patients, 18 and older, with an
      acute exacerbation requiring intravenous antibiotics had a daily FEV1. The
      average time to a 10% increase over their initial sick FEV1 was calculated, as
      well as the time to a new baseline. A total of 25 subjects completed the study.
      Ten of the 25 subjects did not have a sustainable 10% increase in FEV1. Of the 15
      subjects with a sustainable 10% increase in FEV1, it took 5.2 days (+/-4.5) after
      day 1, while a new baseline was achieved on average at 6.6 days (+/-4.8) after
      day 1. Given the wide range of time to a 10% improvement and new baseline, it is
      recommended there should be flexibility in length of intravenous antibiotics in
      CF, not by a preset number.

PMID- 29183161
TI  - Macrophage repolarization using CD44-targeting hyaluronic acid-polylactide
      nanoparticles containing curcumin.
AB  - The aim of this study was to evaluate the efficiency of using a natural
      substance, curcumin, encapsulated in CD44-targeting hyaluronate-polylactide (HA
      PLA) nanoparticles (NPs) for the modulation of macrophage polarity from the pro
      inflammatory M1 to anti-inflammatory M2 phenotype. For this purpose, the
      characterization of the NPs was monitored using 1HNMR, FTIR, DLS and FE-SEM. The
      effects of curcumin-encapsulated HA-PLA NPs on the viability of LPS/IFN-gamma
      stimulated peritoneal macrophages were determined using MTT assay. The cellular
      uptake of free curcumin and nano-formulated curcumin was assessed using confocal
      microscopy. Also, the expression levels of iNOS-2 (M1 marker), Arg-1 (M2 marker)
      and also pro-inflammatory cytokines were measured by real-time PCR. Data showed
      that the nano-formulated curcumin with spherical shape, an average diameter of
      102.5 nm and high cellular uptake was significantly less toxic to peritoneal
      macrophages. Furthermore, the nano-formulated curcumin effectively indicated a
      reduction in iNOS-2 and an increase in Arg-1 levels than free curcumin. The
      change in macrophage phenotype by curcumin-encapsulated HA-PLA NPs could suppress
      the inflammation in LPS/IFN-gamma stimulated macrophages as evidenced by a major
      reduction in pro-inflammatory cytokines. Conclusively, the results suggested that
      the curcumin formulation with CD44-targeting HA-PLA NPs might be a promising
      platform for the treatment of inflammatory diseases.

PMID- 29183162
TI  - Understanding the DSM-5: stasis and change.
AB  - This paper aims to understand the DSM-5 through situating it within the context
      of the historical development of the DSM series. When one looks at the sets of
      diagnostic criteria, the DSM-5 is strikingly similar to the DSM-IV. I argue that
      at this level the DSM has become 'locked-in' and difficult to change. At the same
      time, at the structural, or conceptual, level there have been radical changes,
      for example in the definition of 'mental disorder', in the role of theory and of
      values, and in the abandonment of the multiaxial approach to diagnosis. The way
      that the DSM-5 was constructed means that the overall conceptual framework of the
      classification only barely constrains the sets of diagnostic criteria it
      contains.

PMID- 29183163
TI  - Antimutagenic activity of flavonoids from Sozuku.
AB  - Pinocembrin (1) and cardamonin (2) from Sozuku showed a suppressive effect on umu
      gene expression of SOS response in Salmonella typhimurium TA1535/pSK1002 against
      the mutagen furylfuramide. Compounds 1 and 2 suppressed 52% and 36% of SOS
      inducing activity at a concentration of 0.20 MUmol/mL. The ID50 value of 1 was
      0.18 MUmol/mL. These compounds showed the suppression of 2-amino-3,4
      dimethylimidazo-[4,5-f]quinolone (MeIQ) and UV irradiation-induced SOS response.
      Pinostrobin (3) and 5,7-dimethoxyflavanone (4), methyl ethers of 1, showed
      similar activity to 1 against MeIQ-induced SOS response, but that of
      furylfuramide and UV irradiation were decreased. On the other hand, compounds 1-4
      did not show the suppression of activated MeIQ-induced SOS response. Furthermore,
      compounds 1-4 showed potent antimutagenic activity against MeIQ mutagenesis in
      Ames test using the S. typhimurium TA100 and TA98 strains.

PMID- 29183165
TI  - Cerebral mycotic aneurysms secondary to Streptococcus Agalactiae induced
      infective endocarditis.
AB  - Subarachnoid and intraparenchymal haemorrhages due to cerebral mycotic aneurysms
      are rare and associated with high mortality. Streptococcus agalactiae, is a rare
      cause of endocarditis and there are no reported cases of cerebral mycotic
      aneurysms secondary to this organism. We report a rare case of streptococcus
      agalctiae induced intracranial mycotic aneurysm.

PMID- 29183164
TI  - Network meta-analysis of second-line treatment in metastatic renal cell
      carcinoma: efficacy and safety.
AB  - This paper aims to compare the approved second-line treatment options in
      metastatic renal cell carcinoma. A network meta-analysis (NMA) using the
      frequentist approach and generalized pairwise modeling was computed for the
      approved drugs in this setting. The results of this NMA showed that the
      combination of lenvatinib and everolimus yielded the lowest hazard ratio (HR) for
      progression-free survival (HR: 0.4; 95% CI: 0.21-0.75) and overall survival (HR:
      0.55; 95% CI: 0.30-1.00). The great efficacy of this combination is limited by
      the prevalence of grade 3-4 adverse events (70.6%) leading to treatment
      discontinuation in 17.6%. This NMA is to the best of our knowledge, the first
      analysis of the approved regimens for the second-line treatment of metastatic
      renal cell carcinoma.

PMID- 29183166
TI  - Use of extrusion aids for successful production of Kollidon(r) CL-SF pellets by
      extrusion-spheronization.
AB  - OBJECTIVE: Fine particle ethylcellulose (FPEC) or poly(ethylene oxide) (PEO)
      addition to a Kollidon CL-SF was investigated to address low yield and poor
      sphericity in extruded-spheronized pellets. SIGNIFICANCE: The success of
      crospovidone as a diluent in extrusion-spheronization was dependent on a small
      particle size of the polymer. FPEC aided production of rugged and spherical
      pellets using a large particle size grade, Polyplasdone(r) XL. PEO acted as an
      extrusion-spheronization aid when ethylcellulose was the diluent. These extrusion
      spheronization aids could serve in this role when Kollidon(r) CL-SF (K CL-SF) is
      the diluent. METHODS: The influence of formulation and process variables on
      pellet properties was investigated using design of experiments. A planetary mixer
      was used to prepare powder blends and the wetted mass after addition of water. An
      EXD 60 extruder produced extrudate that was spheronized in a Q230 marumerizer.
      Wet pellets were dried in a forced-air oven. RESULTS: FPEC improved rounding up
      but reduced pellet yield. Poly(ethylene oxide) imparted desired characteristics
      to the wetted mass, the extrudate, and the spheronized pellets. Pellet average
      diameter, yield, sphericity, aspect ratio, friability, and dissolution profile
      were assessed. Equations for pellet characteristics facilitated discussion of the
      influences of factors and their interactions. Optimization was performed on
      pellets that included PEO. CONCLUSIONS: PEO proved to be an exceptional extrusion
      spheronization aid in the preparation of pellets using K CL-SF. It facilitated
      wetted mass extrusion with minimal mass loss to the extruder, and markedly
      improved the sphericity of the pellets produced by marumerization. Immediate
      release pellets were obtained.

PMID- 29183167
TI  - Adding Pertuzumab to Trastuzumab and Taxanes in HER2 positive breast cancer.
AB  - INTRODUCTION: The monoclonal antibody trastuzumab has improved the median disease
      free and overall survival of patients with early stage breast cancer that
      overexpresses the human epidermal growth factor receptor 2 (HER2). Despite this
      advance, some patients experience cancer relapse and novel approaches are always
      needed. One such advance is the monoclonal antibody pertuzumab, which prevents
      dimerisation between members of the HER family of transmembrane glycoprotein
      receptors. Areas covered: In this review, the authors analyse recent research
      which has focused on the development of new HER2 targeting agents for HER2
      positive breast cancer, particularly pertuzumab, and its addition to trastuzumab
      and taxanes. Expert opinion: Pertuzumab has significantly improved disease
      control in patients with advanced HER2 positive breast cancer when added to
      chemotherapy and trastuzumab. Although pertuzumab has also increased response
      rates in the preoperative setting, this has not yet translated into increased
      overall survival. The authors believe that future research should focus on
      improvements in novel biomarkers to select patients for new treatments.

PMID- 29183168
TI  - Minimal Custom Pack Design and Wide-Awake Hand Surgery: Reducing Waste and
      Spending in the Orthopedic Operating Room.
AB  - BACKGROUND: The US health care sector has substantial financial and environmental
      footprints. As literature continues to study the differences between wide-awake
      hand surgery (WAHS) and the more traditional hand surgery with sedation & local
      anesthesia, we sought to explore the opportunities to enhance the sustainability
      of WAHS through analysis of the respective costs and waste generation of the 2
      techniques. METHODS: We created a "minimal" custom pack of disposable surgical
      supplies expressly for small hand surgery procedures and then measured the waste
      from 178 small hand surgeries performed using either the "minimal pack" or the
      "standard pack," depending on physician pack choice. Patients were also asked to
      complete a postoperative survey on their experience. Data were analyzed using 1-
      and 2-way ANOVAs, 2-sample t tests, and Fisher exact tests. RESULTS: As expected,
      WAHS with the minimal pack produced 0.3 kg (13%) less waste and cost $125 (55%)
      less in supplies per case than sedation & local with the standard pack. Pack size
      was found to be the driving factor in waste generation. Patients who underwent
      WAHS reported slightly greater pain and anxiety levels during their surgery, but
      also reported greater satisfaction with their anesthetic choice, which could be
      tied to the enthusiasm of the physician performing WAHS. CONCLUSIONS: Surgical
      waste and spending can be reduced by minimizing the materials brought into the
      operating room in disposable packs. WAHS, as a nascent technique, may provide an
      opportunity to drive sustainability by paring back what is considered necessary
      in these packs. Moreover, despite some initial anxiety, many patients report
      greater satisfaction with WAHS. All told, our study suggests a potentially
      broader role for WAHS, with its concomitant emphases on patient satisfaction and
      the efficient use of time and resources.

PMID- 29183169
TI  - United States Registered Nurse Workforce Report Card and Shortage Forecast: A
      Revisit.
AB  - This is a reevaluation of registered nurse (RN) supply and demand from 2016 to
      2030 using a previously published work forecast model and grading methodology
      with more recent workforce data. There will be a shortage of 154 018 RNs by 2020
      and 510 394 RNs by 2030; the South and West regions will have higher shortage
      ratios than Northeast and Midwest regions. This reflects a nearly 50% overall
      improvement when compared with the authors' prior study, and the low-performing
      states have improved from 18 "D" and 12 "F" grades as published earlier to 13 "D"
      and 1 "F" in this study. Although progress has been made, efforts to foster the
      pipelines for improving the nursing workforce need to be continued.

PMID- 29183171
TI  - Attaining cholesterol goals: will aiming for lower targets improve the score?

PMID- 29183170
TI  - Primary central nervous system lymphoma and glioblastoma differentiation based on
      conventional magnetic resonance imaging by high-throughput SIFT features.
AB  - PURPOSE OF THE STUDY: Due to the totally different therapeutic regimens needed
      for primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM),
      accurate differentiation of the two diseases by noninvasive imaging techniques is
      important for clinical decision-making. MATERIALS AND METHODS: Thirty cases of
      PCNSL and 66 cases of GBM with conventional T1-contrast magnetic resonance
      imaging (MRI) were analyzed in this study. Convolutional neural networks was used
      to segment tumor automatically. A modified scale invariant feature transform
      (SIFT) method was utilized to extract three-dimensional local voxel arrangement
      information from segmented tumors. Fisher vector was proposed to normalize the
      dimension of SIFT features. An improved genetic algorithm (GA) was used to
      extract SIFT features with PCNSL and GBM discrimination ability. The data-set was
      divided into a cross-validation cohort and an independent validation cohort by
      the ratio of 2:1. Support vector machine with the leave-one-out cross-validation
      based on 20 cases of PCNSL and 44 cases of GBM was employed to build and validate
      the differentiation model. RESULTS: Among 16,384 high-throughput features, 1356
      features show significant differences between PCNSL and GBM with p < 0.05 and 420
      features with p < 0.001. A total of 496 features were finally chosen by improved
      GA algorithm. The proposed method produces PCNSL vs. GBM differentiation with an
      area under the curve (AUC) curve of 99.1% (98.2%), accuracy 95.3% (90.6%),
      sensitivity 85.0% (80.0%) and specificity 100% (95.5%) on the cross-validation
      cohort (and independent validation cohort). CONCLUSIONS: Since the local voxel
      arrangement characterization provided by SIFT features, proposed method produced
      more competitive PCNSL and GBM differentiation performance by using conventional
      MRI than methods based on advanced MRI.

PMID- 29183172
TI  - Endoscopic submucosal dissection of gastric neoplasms using a snare tip.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) enables the complete removal
      of gastric lesions regardless of tumor size. ESD is typically performed using one
      of several available electrocautery knives and endoscopic mucosal resection (EMR)
      is performed using a diathermic snare. We aimed to investigate the clinical
      outcomes and complications in patients in whom a snare tip was used for ESD.
      MATERIALS AND METHODS: We retrospectively evaluated the medical records of 30
      patients who underwent removal of a gastric lesion using a snare tip by ESD or
      hybrid ESD (ESD with snaring). For hybrid ESD, snaring was performed after an
      adequate submucosal dissection. The clinical outcomes according to the endoscopic
      procedure performed were evaluated. RESULTS: ESD was performed in 12 patients and
      hybrid ESD was performed in 26 patients. Overall en-bloc and complete resection
      rates were both 97.4%. There was one case where piece-meal resection was
      performed in the hybrid ESD group. There were no procedure related complications
      such as perforation or bleeding. The mean specimen size was 2.8 +/- 0.6 cm in the
      ESD group and 2.3 +/- 0.5 cm in the hybrid ESD group (p = .031). The mean
      procedure time did not differ between the two methods (12.8 min in ESD and 9.7
      min in hybrid ESD, p = .060). CONCLUSIONS: The snare tip can be used as an
      electrocautery knife to incise the mucosa and dissect the submucosa during
      removal of a gastric lesion.

PMID- 29183173
TI  - Evaluation for shunted pouches of cavernous sinus dural arteriovenous fistula and
      the treatment outcome of transvenous embolization.
AB  - Background This study aimed to evaluate the detailed location and the number
      (single or multiple) of cavernous sinus dural arteriovenous fistula (CSDAVF)
      shunted pouches as well as the relationship between the characteristics of
      shunted pouch(es) and the treatment outcome of transvenous embolization for
      CSDAVF. Methods A total of 23 consecutive patients with CSDAVFs who underwent
      angiogram and transvenous embolization were retrospectively analyzed. Shunted
      pouches were assessed using three-dimensional angiogram and multiplanar
      reformatted image obtained from the rotational angiogram data. Results Of the 23
      patients with CSDAVFs, 40 shunted pouches were identified. Twelve CSDAVFs had a
      single shunted pouch, and 11 had multiple shunted pouches. The mean CSDAVF with
      multiple shunted pouches was 2.5. The shunted pouches were more often found in
      the posterior compartment of the CS, which was connected with the intercavernous
      sinus (23/40; 57.5%). In 12 CSDAVFs with a single shunted pouch, 10 were treated
      with selective embolization and complete occlusion was achieved during the follow
      up. Two CSDAVFs with single shunted pouch were just observed without
      intervention, and DAVFs disappeared spontaneously during the follow-up period. In
      11 CSDAVFs with multiple shunted pouches, eight were treated with selective
      embolization and three with sinus embolization. In six of eight (75%), complete
      occlusion was achieved following selective embolization, but two of eight (25%)
      recurred and required retreatment. Conclusions Rotational angiography data
      suggested that the shunted pouches of CSDAVFs were mostly located in the
      posterior compartment of the CS connected with the intercavernous sinus.
      Selective embolization for CSDAVFs with a single shunted pouch is the first-line
      treatment alternative to sinus packing, and selective embolization with multiple
      shunted pouches will be a considerable treatment option.

PMID- 29183174
TI  - Limit of intraoperative near-infrared spectroscopy monitoring during endovascular
      thrombectomy in acute ischemic stroke.
AB  - Endovascular thrombectomy is recommended for a persistent ischemic penumbra if
      recanalization cannot be achieved by the intravenous (IV) administration of
      recombinant tissue-plasminogen activator (rt-PA) alone. Although endovascular
      thrombectomy is a powerful treatment for major cerebral artery occlusion, the
      monitoring of recanalization and reperfusion during acute ischemic stroke
      presents a therapeutic challenge, and a previous study reported the usefulness of
      near-infrared spectroscopy (NIRS) for intraoperative monitoring during emergency
      endovascular thrombectomy for acute large ischemic stroke. Here we present our
      experience with a relevant case series. We applied NIRS monitoring during
      endovascular thrombectomy in two patients with large ischemic stroke following
      carotid artery occlusion and one patient with a non-large ischemic stroke caused
      by a distal middle cerebral artery (MCA) occlusion. In the patients with large
      ischemic stroke, complete recanalization of the internal carotid artery was
      achieved, and NIRS revealed a very good regional oxygen saturation (rSO2)
      response. By contrast, in the patient with non-large ischemic stroke, the rSO2
      did not change, despite complete recanalization of the distal MCA. Our findings
      suggest the limited usefulness of intraoperative NIRS monitoring during emergency
      endovascular thrombectomy for non-large acute ischemic stroke caused by a distal
      MCA occlusion. However, intraoperative NIRS monitoring could be used practically
      to detect recanalization of the major artery during thrombectomy and early IV rt
      PA administration in cases involving major artery occlusion.

PMID- 29183175
TI  - Economic evaluation of medical tests at the early phases of development: a
      systematic review of empirical studies.
AB  - INTRODUCTION: There is little specific guidance on the implementation of cost
      effectiveness modelling at the early stage of test development. The aim of this
      study was to review the literature in this field to examine the methodologies and
      tools that have been employed to date. Areas Covered: A systematic review to
      identify relevant studies in established literature databases. Five studies were
      identified and included for narrative synthesis. These studies revealed that
      there is no consistent approach in this growing field. The perspective of
      patients and the potential for value of information (VOI) to provide information
      on the value of future research is often overlooked. Test accuracy is an
      essential consideration, with most studies having described and included all
      possible test results in their analysis, and conducted extensive sensitivity
      analyses on important parameters. Headroom analysis was considered in some
      instances but at the early development stage (not the concept stage). Expert
      commentary: The techniques available to modellers that can demonstrate the value
      of conducting further research and product development (i.e. VOI analysis,
      headroom analysis) should be better utilized. There is the need for concerted
      efforts to develop rigorous methodology in this growing field to maximize the
      value and quality of such analysis.

PMID- 29183176
TI  - Incidence of maternal tachycardia during the second stage of labor: a prospective
      observational cohort study.
AB  - OBJECTIVE: To our knowledge, this is the largest prospective study reporting on
      maternal heart rate (MHR) levels in laboring women (30 patients), and maternal
      tachycardia that is a potential risk factor in fetal monitoring confusion. Our
      objective was to analyze a large population of contiguous laboring patients and
      to assess the MHR levels attained during the second stage. METHODS: We performed
      a prospective study that analyzed MHR levels of second-stage laboring patients
      evaluating numerous predisposing maternal conditions. Univariate and stepwise
      multivariate logistic regression analysis were performed. RESULTS: A total of
      1105 contiguous patients were analyzed and 33.9% had a sustained MHR >=100; 18.8%
      had an MHR >=110; and 9.1% had an MHR >=120. Multivariate analysis of all
      potential predisposing maternal conditions did not reveal any specific variable
      as uniformly significant for predicting maternal tachycardia across all levels of
      analysis. CONCLUSIONS: The incidence of maternal tachycardia in the second stage
      of labor is common. We recommend that if the MHR is >=100 during labor, the
      simultaneous maternal and fetal heart rate (FHR) monitoring will be used to
      minimize the potential for fetal monitoring confusion and risking poor fetal
      outcome if the fetus is in distress.

PMID- 29183177
TI  - Low Apgar scores in term newborns and long-term gastro-intestinal morbidity: a
      population-based cohort study with up to 18 years of follow-up.
AB  - INTRODUCTION: Low Apgar scores (<7) measured at age 5 minutes can predict short
      term infant morbidity and mortality. Although an association exists between low
      Apgar scores and neuropsychological disorders, other childhood disorders were not
      thoroughly studied. We aimed to study the possible association between low 5
      minute Apgar scores in term newborns and their long-term childhood
      gastrointestinal (GI) morbidity. METHODS: A population-based cohort analysis was
      performed comparing total and different subtypes of GI-related pediatric
      hospitalizations among newborns with normal (>=7) and low (<7) 5-minute Apgar
      scores. The analysis included all term singletons born between the years 1999 and
      2014 at a single tertiary regional medical center. Infants with congenital
      malformations, multiple gestations, and all perinatal deaths were excluded from
      the analysis. GI-related morbidities included hospitalizations involving a
      predefined set of ICD-9 codes, as recorded in the hospital computerized files. A
      Kaplan-Meier survival curve was constructed to compare the cumulative GI
      morbidity, and a Cox proportional hazards model was used to adjust for
      confounders. RESULTS: The study population, including 223 244 term singletons,
      was followed for an average of 10.02 +/- 6.0 years (0-18 years, median 10.25)
      following discharge from birth hospitalization. Low 5-minute Apgar scores were
      recorded in 585 (0.3%) newborns. Incidence of GI-related hospitalizations was
      higher among the low versus the normal 5-minute Apgar score group (7.4 versus
      5.2%; 8.6/1000 person years (PY) versus 5.2/1000 PY, respectively; p = .02; odds
      ratio =1.66, 95%CI 1.36-1.96). The association remained significant and
      independent while adjusting for gestational age, fetal weight, offspring gender,
      maternal age, maternal smoking, hypertension, and diabetes (Adjusted HR =1.57,
      95%CI 1.16-2.12, p = .003). CONCLUSIONS: Low 5 minutes Apgar score is associated
      with an increased risk for long-term pediatric GI morbidity of the offspring. Our
      results suggest that Apgar scores can be used as a possible predictor for long
      term pediatric morbidities and thus may necessitate appropriate surveillance in
      this vulnerable group of children.

PMID- 29183178
TI  - Health providers' communication skills training affects hypertension outcomes.
AB  - OBJECTIVE: Hypertension is a common cardiovascular risk factor within the Iranian
      population, and this may be improved through changes in lifestyle. We aimed at
      improving hypertension outcomes and health literacy skills among hypertensive
      patients through communication skills training targeting health providers.
      METHODS: A randomized controlled trial method was used to enroll 35 health
      providers and 240 hypertensive patients attending community-based healthcare
      practices in the Mashhad, Iran. We evaluated the effects of a communication
      skills intervention for primary care providers compared to usual care controls,
      on the hypertension outcomes, patient medication adherence, and self-efficacy,
      assessed at baseline and post-intervention. Bivariate analysis and the regression
      model were used to assess whether the health provider training improved outcomes.
      RESULTS: Majority of participating patients were female (77.3%), less than high
      school education (80.3%), married (82.3%), and low income (82.3%), with mean age
      of 37 years. Following the educational intervention, there was a significant
      improvement (p < 0.05) in patient communication skills, self-efficacy, adherence
      to medication, and hypertension outcomes in the intervention compared to the
      control group. CONCLUSIONS: The brief communication skills training for health
      care providers appear to be an efficient way to improve patient-provider
      communication skills and hypertension outcome among patients with uncontrolled
      BP.

PMID- 29183179
TI  - Taking a prebiotic approach to early immunomodulation for allergy prevention.
AB  - INTRODUCTION: With increasing focus on nutritional strategies to counter the
      rising global burden of allergic disease, there has been a particular focus on
      prebiotic nutrients that are selectively utilized by host microorganisms to
      confer potential immunomodulatory benefits for disease prevention. Areas covered:
      In this review we examine maternal and infant dietary sources of prebiotics with
      a particular focus on non-digestible oligosaccharides, which undergo microbial
      fermentation by commensal gut bacteria to produce short chain fatty acids (SCFA).
      We summarize the major proposed health benefits of SCFA in early life immune
      development, together with the current evidence for maternal and/or infant
      prebiotic consumption in abrogating the risk of early childhood allergic
      diseases. Medline searches (to August 2017) for English language papers included
      prebiotics and SCFA search terms in combination with relevant allergic disease
      terms. Expert commentary: The potential beneficial effects of maternal and infant
      prebiotic consumption for allergy prevention are promising, but still require
      considerably further investigation through high-quality randomised controlled
      trials and detailed mechanistic studies. This should be coupled with more
      research on the biological effects of human milk oligosaccharides (HMO),
      including their influence on infant immune development, and the maternal
      nutritional factors that optimise HMO composition and infant outcomes.

PMID- 29183180
TI  - A spotlight on the management of complications associated with myeloproliferative
      neoplasms: a clinician's perspective.
AB  - INTRODUCTION: Myeloproliferative neoplasms (MPNs) are associated with a variety
      of symptoms and signs which cause major morbidity for the patients. The disorders
      are associated with increased incidence of thromboembolic and hemorrhagic events
      which can lead to complications and shortened life expectancy. Areas covered:
      Using systematic literature review and expert clinical and research experience
      the authors discuss strategies for the management of symptoms and signs including
      pruritus, fatigue, splenomegaly, and cytopenia. Cytoreduction including
      treatments to inhibit the JAK/STAT pathway are considered. Pathogenesis and
      prevention and treatment of thrombotic and hemorrhagic events and their
      management is addressed and the suggested management of the special situations
      such as surgery and pregnancy are discussed. Expert commentary: Management of
      disease has traditionally focused on symptom treatment and complication
      prevention but the discovery of driver mutations has led to treatments aiming to
      eliminate the clone, which should be the ultimate goal of therapy. A future
      challenge is to develop safe and effective MPN therapy and to personalize
      therapy.

PMID- 29183181
TI  - Maternal anemia during pregnancy and small for gestational age: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: Anemia is a major public health and nutritional problem in the world.
      Studies have reported the relationship between anemia during pregnancy and small
      for gestational age (SGA). Therefore, the present systematic review and meta
      analysis was conducted to determine the relationship between maternal anemia
      during pregnancy and SGA. METHOD: This meta-analysis was conducted without time
      limit until April 2017 based on the PRISMA protocol. Several international
      databases including Cochrane, Scopus, Web of Science (ISI), Pubmed, Embase, and
      Google Scholar search engine were searched independently by two researchers. The
      keywords include: anemia, pregnant women, gestational age, and pregnancy. The
      relative risk (RR) and 95% confidence interval were estimated regarding to the
      significance of the I2 index based on the random effects model. Data were
      analyzed using Comprehensive Meta-Analysis Software version 2. RESULTS: Ten
      studies with a sample size including 620 080 pregnant women entered the meta
      analysis process. The overall relationship between maternal anemia during
      pregnancy and SGA was not significant (RR = 1.11 [95%CI: 0.99-1.24, p = .074]).
      The relationship between anemia during pregnancy and SGA based on pregnancy
      trimester showed that maternal anemia was significant in the first trimester, (RR
      = 1.11 [95%CI: 1-1.22, p = .044]), but this relationship was not significant in
      the second trimester (RR = 1.11 [95%CI: 0.85-1.18, p = .91]). CONCLUSIONS:
      Maternal anemia in the first trimester of pregnancy can be considered as a risk
      factor for negative pregnancy outcomes (SGA).

PMID- 29183182
TI  - Cost effectiveness of human papilloma virus vaccination in low and middle income
      countries: a systematic review of literature.
AB  - INTRODUCTION: Low and middle income countries (LMICs) bear more than 50% of the
      current cervical cancer burden over the last decade with linkages to lack of HPV
      vaccination, high levels of poverty, illiteracy and nonexistent or poor screening
      programs. Governments of LMICs need enough convincing evidence that HPV
      vaccination will be more cost-effective in reducing the scourge of cervical
      cancer. Area covered: A systematic review to identify suitable studies from
      MEDLINE(via PubMed), EMBASE and Electronic search through GOOGLE for original and
      review articles from 2007 to 2014 on cost-effectiveness of human papilloma virus
      vaccination of pre-adolescent girls in LMICs was conducted. A total of 19 full
      articles were finally selected and reviewed after screening out those not
      consistent with the inclusion and exclusion criteria. Expert commentary: Most
      studies on cost-effectiveness of HPV vaccine in LMICs show that lowering cost of
      HPV vaccination with or without Pap smear screening is cost-effective in areas
      with high incidence of cervical cancer.

PMID- 29183183
TI  - Peer group reflection on student ratings stimulates clinical teachers to generate
      plans to improve their teaching.
AB  - BACKGROUND: Previous studies have demonstrated that student ratings of a
      teachers' performance do not incentivize clinical teachers to reflect critically
      and generate plans to improve their teaching. Peer group reflection might offer a
      solution in mediating this change. AIM: To investigate: (a) to which extent
      clinical teachers perceive self-evaluation, student ratings and peer group
      reflection effective; and (b) whether additional peer group reflection fosters
      critical reflection and the translation of feedback into concrete plans of
      action. METHOD: We conducted a quasi-experiment, inviting two groups of 10
      clinical teachers each (1) to complete a self-evaluation and (2) subsequently
      examine their student ratings. One group participated in (3) an additional peer
      group reflection meeting. All participants were finally requested to define plans
      for improvement and evaluate each activity's effectiveness. RESULTS: Participants
      perceived all three activities to be effective. Levels of reflection did not
      differ across the two groups. However, participation in peer group reflection did
      result in generating more concrete plans to change clinical teaching.
      CONCLUSIONS: Peer group reflection on student ratings shows promise as tool to
      assist clinical teachers in generating plans for improvement. Future research
      should focus on whether teaching indeed improves with the introduction of peer
      group reflection.

PMID- 29183184
TI  - Third trimester ultrasound for fetal macrosomia: optimal timing and institutional
      specific accuracy.
AB  - PURPOSE: To determine the performance of third trimester ultrasound in women with
      suspected fetal macrosomia. MATERIALS AND METHODS: We performed a retrospective
      cohort study of fetal ultrasounds from January 2004 to December 2014 with
      estimated fetal weight (EFW) between 4000 and 5000 g. We determined accuracy of
      birth weight prediction for ultrasound performed at less than and greater than 38
      weeks, accounting for diabetic status and time between ultrasound and delivery.
      RESULTS: There were 405 ultrasounds evaluated. One hundred and twelve (27.7%)
      were performed at less than 38 weeks, 293 (72.3%) at greater than 38 weeks, and
      91 (22.5%) were performed in diabetics. Sonographic identification of EFW over
      4000 g at less than 38 weeks was associated with higher correlation between EFW
      and birth weight than ultrasound performed after 38 weeks (71.5 versus 259.4 g, p
      < .024). EFW to birth weight correlation was within 1.7% of birth weight for
      ultrasound performed less than 38 weeks and within 6.5% of birth weight for
      ultrasound performed at greater than 38 weeks. CONCLUSIONS: Identification of EFW
      with ultrasound performed less than 38 weeks has greater reliability of
      predicting fetal macrosomia at birth than measurements performed later in
      gestation. EFW to birth weight correlation was more accurate than previous
      reports.

PMID- 29183185
TI  - The effect of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry instrumentation parameters on the matrix-assisted laser
      desorption/ionization simulated size exclusion chromatography number-mass,
      average-weight and polydispersity values of dextran against corresponding values
      obtained by size exclusion chromatography.
AB  - The matrix-assisted laser desorption/ionization simulated size exclusion
      chromatography (SECPC) average-number mass, weight average and polydispersity of
      dextran 1000 were determined by matrix-assisted laser desorption/ionization
      (MALDI) time-of-flight (TOF) mass spectrometry. The instrument parameters were
      varied and the SECPC value determined via the Bruker XMASS software was compared
      to the value obtained from aqueous-phase size exclusion chromatography. The
      aqueous-phase size exclusion chromatography values for average-number mass,
      weight average and polydispersity were 1223 Da, 1500 Da and 1.23 (1010 Da, 1270
      Da and 1.26 from manufacturer), whereas the SECPC value varied on the
      instrumental parameters. The factors that had the greatest effect on the average
      number mass, weight average and polydispersity were: (most effect on SECPC value)
      laser attenuation > matrix-analyte molar concentration > matrix-analyte molar
      ratios > delay extraction time > solvent-system composition > detector delay
      (least effect on SECPC value). The oligosaccharide signal distribution as a
      function of laser attenuation indicate that two distinct regions exist in dextran
      1000, where one corresponds to the higher mass oligosaccharides (hexasaccharide
      or greater), while another region corresponds to lower oligosaccharides (tetra
      saccharide). This distribution depends upon the crystallization of the biopolymer
      and the efficiency of desorption/ionization, which yields the SECPC value. There
      was broad agreement between the SECPC values and size exclusion chromatography
      values for dextran, although the polydispersity indicated by SECPC was less than
      size exclusion chromatography (1.10 vs. 1.26). It can be shown that for narrow
      polydisperse biopolymers the instrumental conditions are less critical in the
      determination of average-number mass, weight average and polydispersity, although
      the SECPC Mn, and weight average values are often higher than the corresponding
      values obtained by aqueous-phase size exclusion chromatography.

PMID- 29183186
TI  - A new approach for accurate mass assignment on a multi-turn time-of-flight mass
      spectrometer.
AB  - A simple, effective accurate mass assignment procedure for a time-of-flight mass
      spectrometer is desirable. External mass calibration using a mass calibration
      standard together with an internal mass reference (lock mass) is a common
      technique for mass assignment, however, using polynomial fitting can result in
      mass-dependent errors. By using the multi-turn time-of-flight mass spectrometer
      infiTOF-UHV, we were able to obtain multiple time-of-flight data from an ion
      monitored under several different numbers of laps that was then used to calculate
      a mass calibration equation. We have developed a data acquisition system that
      simultaneously monitors spectra at several different lap conditions with on-the
      fly centroid determination and scan law estimation, which is a function of
      acceleration voltage, flight path, and instrumental time delay. Less than 0.9 mDa
      mass errors were observed for assigned mass to charge ratios ( m/z) ranging
      between 4 and 134 using only 40Ar+ as a reference. It was also observed that
      estimating the scan law on-the-fly provides excellent mass drift compensation.

PMID- 29183187
TI  - Peter J Derrick and the Grand Scale 'Magnificent Mass Machine' mass spectrometer
      at Warwick.
AB  - The value of the Grand Scale 'Magnificent Mass Machine' mass spectrometer in
      investigating the reactivity of ions in the gas phase is illustrated by a brief
      analysis of previously unpublished work on metastable ionised n-pentyl methyl
      ether, which loses predominantly methanol and an ethyl radical, with very minor
      contributions for elimination of ethane and water. Expulsion of an ethyl radical
      is interpreted in terms of isomerisation to ionised 3-pentyl methyl ether, via
      distonic ions and, possibly, an ion-neutral complex comprising ionised
      ethylcyclopropane and methanol. This explanation is consistent with the closely
      similar behaviour of the labelled analogues, C3H7CH2CD2OCH3+. and
      C3H7CD2CH2OCH3+., and is supported by the greater kinetic energy release
      associated with loss of ethane from ionised n-propyl methyl ether compared to
      that starting from directly generated ionised 3-pentyl methyl ether.

PMID- 29183189
TI  - Editor's personal foreword.

PMID- 29183188
TI  - Prof. Peter J Derrick (1945-2017).

PMID- 29183190
TI  - Basic poly(propylene glycols) as reference compounds for internal mass
      calibration in positive-ion matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Basic poly(propylene glycols), commercially available under the trade name
      Jeffamine, are evaluated for their potential use as internal mass calibrants in
      matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry. Due
      to their basic amino endgroups Jeffamines are expected to deliver [M+H]+ ions in
      higher yields than neutral poly(propylene glycols) or poly(ethylene glycols).
      Aiming at accurate mass measurements and molecular formula determinations by
      matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry,
      four Jeffamines (M-600, M-2005, D-400, D-230) were thus compared. As a result,
      Jeffamine M-2005 is introduced as a new mass calibrant for positive-ion matrix
      assisted laser desorption/ionization-time-of-flight-mass spectrometry in the
      range of m/z 200-1200 and the reference mass list is provided. While Jeffamine M
      2005 is compatible with alpha-cyano-4-hydroxycinnamic acid, 2,5-dihydroxybenzoic
      acid, and 2-[(2 E)-3-(4- tert-butylphenyl)-2-methylprop-2-enylidene]malonitrile
      matrix, its use in combination with 2-[(2 E)-3-(4- tert-butylphenyl)-2-methylprop
      2-enylidene]malonitrile provides best results due to low laser fluence
      requirements. Applications to PEG 300, PEG 600, the ionic liquid
      trihexyl(tetradecyl)-phosphonium tris(pentafluoroethyl)-trifluorophosphate, and
      [60]fullerene demonstrate mass accuracies of 2-5 ppm.

PMID- 29183191
TI  - Mechanisms governing the fragmentation of glycerophospholipids containing choline
      and ethanolamine polar head groups.
AB  - Glycerophospholipids are the major amphiphilic molecules found in the plasma
      membrane bilayer of all vertebrate cells. Involved in many biological processes,
      their huge structural diversity and large concentration scale make their thorough
      characterization extremely difficult in complex biological matrices. Mass
      spectrometry techniques are now recognized as being among the most powerful
      methods for the sensitive and comprehensive characterization of lipids. Depending
      on the experimental conditions used during electrospray ionization mass
      spectrometry experiments, glycerophospholipids can be detected as different
      molecular species (e.g. protonated, sodiated species) when analyzed either in
      positive or negative ionization modes or by direct introduction or hyphenated
      mass spectrometry-based methods. The observed ionized forms are characteristic of
      the corresponding phospholipid structures, and their formation is highly
      influenced by the polar head group. Although the fragmentation behavior of each
      phospholipid class has already been widely studied under low collision energy,
      there are no established rules based on charge-induced dissociation mechanisms
      for explaining the generation of fragment ions. In the present paper, we
      emphasize the crucial roles played by ion-dipole complexes and salt bridges
      within charge-induced dissociation processes. Under these conditions, we were
      able to readily explain almost all the fragment ions obtained under low-energy
      collision-induced dissociation for particular glycerophospholipids and
      lysoglycerophospholipids species including glycerophosphatidylcholines and
      glycerophosphatidylethanolamines. Thus, in addition to providing a basis for a
      better comprehension of phospholipid fragmentation processes, our work also
      highlighted some potentially new relevant diagnostic ions to signal the presence
      of particular lipid species.

PMID- 29183192
TI  - Proton-induced reactions of [2.2]-paracyclophane in the gas phase. A study by FT
      ICR-spectrometry and DFT calculation.
AB  - The reactions of the [2-2]-paracyclophane 1 and the [2-2]-metaparacyclopane 2 in
      the gas phase after protonation by CI(CH4) or CI(I-C4H10) were studied by FT-ICR
      mass spectrometry. The ions C16H17+ produced in the external ion source of the FT
      ICR instrument were transferred into the ICR cell containing the neutral
      reactant, and the reactions were analyzed measuring the efficiency of the
      transfer of a proton to a series of bases with known proton affinity and gas
      phase basicity as well as the efficiency of the ion-molecule reaction with ethyl
      vinyl ether. Both reaction types show that the ions C16H17+ produced by chemical
      ionization (CI) consist of two sets of isomeric ions A and B which exhibit
      distinctly different behavior on deprotonation and of the reaction with ethyl
      methyl ether. Isomer(s) A (about 65% of the ion population) react efficiently
      with this vinyl ether by an addition/elimination process typical of primary and
      secondary benzylic carbenium ions, while isomer B (about 35% of the ion
      population) undergoes only an ineffective deprotonation by the vinyl ether. By
      bracketing deprotonation, it is shown that A is actually composed of two isomers
      A1 and A2 with slightly different proton affinity and gas phase basicity. These
      two ions have been identified using CA-mass spectrometry as protonated 3
      phenethylstyrene (A1) and protonated 4-phenethylstyrene (A2). The CA-mass
      spectrum of the isomer B indicated that these ions C16H17+ correspond to
      protonated 1-(ethyl phenyl)-1-phenyl-ethene. This agrees with the rather strong
      basicity of the conjugated base of ions B, which results in a slow deprotonation.
      A protonated 1-(ethyl phenyl)-1-phenyl-ethene can arise from a protonated 2
      phenethylstyrene by H- and subsequent phenyl shifts, but requires the preceding
      rearrangement of the protonated [2.2]-paracyclophane into the protonated isomer
      "[2.2]-orthocyclophane" - the 1,5-dibenzocyclooctadiene. The possibility of such
      a deep-sited rearrangement was studied by the computation of the relevant
      reaction routes applying DFT-methods at the level B3LYP/6-311+g(3d,2p)//B3LYP/3
      21g) to analyze the reaction mechanisms.

PMID- 29183193
TI  - Mass spectrometric characterization of protein structures and protein complexes
      in condensed and gas phase.
AB  - Proteins are essential for almost all physiological processes of life. They serve
      a myriad of functions which are as varied as their unique amino acid sequences
      and their corresponding three-dimensional structures. To fulfill their tasks,
      most proteins depend on stable physical associations, in the form of protein
      complexes that evolved between themselves and other proteins. In solution
      (condensed phase), proteins and/or protein complexes are in constant energy
      exchange with the surrounding solvent. Albeit methods to describe in-solution
      thermodynamic properties of proteins and of protein complexes are well
      established and broadly applied, they do not provide a broad enough access to
      life-science experimentalists to study all their proteins' properties at leisure.
      This leaves great desire to add novel methods to the analytical biochemist's
      toolbox. The development of electrospray ionization created the opportunity to
      characterize protein higher order structures and protein complexes rather
      elegantly by simultaneously lessening the need of sophisticated sample
      preparation steps. Electrospray mass spectrometry enabled us to translate
      proteins and protein complexes very efficiently into the gas phase under mild
      conditions, retaining both, intact protein complexes, and gross protein
      structures upon phase transition. Moreover, in the environment of the mass
      spectrometer (gas phase, in vacuo), analyte molecules are free of interactions
      with surrounding solvent molecules and, therefore, the energy of inter- and
      intramolecular forces can be studied independently from interference of the
      solvating environment. Provided that gas phase methods can give information which
      is relevant for understanding in-solution processes, gas phase protein structure
      studies and/or investigations on the characterization of protein complexes has
      rapidly gained more and more attention from the bioanalytical scientific
      community. Recent reports have shown that electrospray mass spectrometry provides
      direct access to six prime protein complex properties: stabilities, compositions,
      binding surfaces (epitopes), disassembly processes, stoichiometries, and
      thermodynamic parameters.

PMID- 29183194
TI  - Multidimensional mass spectrometry characterization of isomeric biodegradable
      polyesters.
AB  - The biodegradable polyester copolymer poly(propylene fumarate) (PPF) is
      increasingly utilized in bone tissue engineering studies due to its suitability
      as inert cross-linkable scaffold material. The well-defined poly(propylene
      fumarate) oligomers needed for this purpose are synthesized by post
      polymerization isomerization of poly(propylene maleate), which is prepared by
      ring opening polymerization of maleic anhydride and propylene oxide. In this
      study, multidimensional mass spectrometry methodologies, interfacing matrix
      assisted laser desorption ionization and electrospray ionization with mass
      analysis, tandem mass spectrometry fragmentation and/or ion mobility mass
      spectrometry, have been employed to characterize the composition, end groups,
      chain connectivity and isomeric purity of the isomeric copolyesters
      poly(propylene maleate)and poly(propylene fumarate). It is demonstrated that the
      polymerization catalyst is incorporated into the polymer chain (as the initiating
      chain end) and that the poly(propylene maleate) to poly(propylene fumarate)
      isomerization using an amine base proceeds with quantitative yield. Hydrolytic
      degradation is shown not to alter the double bond geometry of the poly(propylene
      fumarate) or poly(propylene maleate) chains.

PMID- 29183195
TI  - Analytical techniques for the characterization of Antibody Drug Conjugates:
      Challenges and prospects.
AB  - Antibody drug conjugates are increasingly being researched for the treatment of
      cancer. Accurate and reliable characterization of ADCs is inevitable for their
      development as potential therapeutic agent. Different analytical techniques have
      been used in order to decipher heterogeneous nature of antibody drug conjugates,
      enabling successful characterization. This review will summarize specially three
      major analytical tools i.e. UV-Vis spectroscopy, liquid chromatography, and mass
      spectrometry used in characterization of antibody drug conjugates. In this
      review, major challenges during analysis due to the inherent features of
      analytical techniques and antibody drug conjugates are summarized along with the
      modifications intended to address each challenge.

PMID- 29183196
TI  - Substituent effects in the decarboxylation reactions of coordinated
      arylcarboxylates in dinuclear copper complexes, [(napy)Cu2(O2CC6H4X)]+ ?.
AB  - A combination of gas-phase ion trap mass spectrometry experiments and density
      functional theory (DFT) calculations have been used to examine the role of
      substituents on the decarboxylation of 25 different coordinated aromatic
      carboxylates in binuclear complexes, [(napy)Cu2(O2CC6H4X)]+, where napy is the
      ligand 1,8-naphthyridine (molecular formula, C8H6N2) and X = H and the ortho (
      o), meta ( m) and para ( p) isomers of F, Br, CN, NO2, CF3, OAc, Me and MeO. Two
      competing unimolecular reaction pathways were found: decarboxylation to give the
      organometallic cation [(napy)Cu2(C6H4X)]+ or loss of the neutral copper benzoate
      to yield [(napy)Cu]+. The substituents on the aryl group influence the branching
      ratios of these product channels, but decarboxylation is always the dominant
      pathway. Density functional theory calculations reveal that decarboxylation
      proceeds via two transition states. The first enables a change in the
      coordination mode of the coordinated benzoate in [(napy)Cu2(O2CC6H4X)]+ from the
      thermodynamically favoured O, O-bridged form to the O-bound form, which is the
      reactive conformation for the second transition state which involves extrusion of
      CO2 with concomitant formation of the CO2 coordinated organometallic cation,
      [(napy)Cu2(C6H4X)(CO2)]+, which then loses CO2 in the final step to yield
      [(napy)Cu2(C6H4X)]+. In all cases the barrier is highest for the second
      transition state. The o-substituted benzoates show a lower activation energy than
      the m-substituted ones, while the p-substituted ones have the highest energy,
      which is consistent with the experimentally determined normalised collision
      energy required to induce fragmentation of [(napy)Cu2(O2CC6H4X)]+.

PMID- 29183197
TI  - Proton affinities and ion enthalpies.
AB  - Proton affinities of a number of alkyl acetates (CH3-C(=O)-OR) and of methyl
      alkanoates (R-C(=O)-OCH3, R=H, alkyl) have been assembled from the literature or
      measured using the kinetic method. It was observed that the proton affinities for
      the isomeric species CH3-C(=O)-OR and R-C(=O)-OCH3 are almost identical, an
      unexpected result as the charge in these protonated ester molecules is largely at
      the keto carbon atom and so this site should be more sensitive to alkyl
      substitution. Analysis of the data, including those from lone pair ionisation and
      core-electron ionisation experiments available from the literature, indicate that
      after protonation, extensive charge relaxation (or polarisation) takes place (as
      is also the case, according to the literature, after core-electron ionisation).
      By contrast, after lone pair ionisation, which results in radical cations, such
      relaxation processes are relatively less extensive. As a consequence, changes in
      ion enthalpies of these protonated molecules follow more closely the changes in
      neutral enthalpies, compared with changes in enthalpies of the corresponding
      radical cations, formed by electron detachment. Preliminary analyses of published
      energetic data indicate that the above finding for organic esters may well be
      another example of a more general phenomenon.

PMID- 29183198
TI  - Evaluation of calculated negative mode ion mobilities of small molecules in air.
AB  - Ion mobility spectrometry is a well-known technique employed for the detection
      and analysis of gaseous substances. In pharmaceutical applications, it is
      furthermore used for structural analysis of compounds, especially in combination
      with mass spectrometry. In this field, the comparison of calculated collision
      cross sections and ion mobilities of theoretic model compounds with experimental
      values measured with ion mobility spectrometers helps to determine the compound's
      structure. For positive mode ion mobility spectrometry, the calculated mobilities
      using the Trajectory Method show in general a deviation of 10% or less from
      experimental values. In this article, it was analyzed how well the calculated
      values reproduce the experimental values obtained with negative mode ion mobility
      spectrometry including symmetric and asymmetric analyte clusters. Furthermore,
      the influence of four different partial charge models on the results was
      investigated.

PMID- 29183199
TI  - Exploration of doubtful cases of leucine and isoleucine discrimination in mass
      spectrometric peptide sequencing by electron-transfer and higher-energy collision
      dissociation-based method.
AB  - Electron-transfer dissociation (ETD) and electron-transfer and higher-energy
      collision dissociation (EThcD) spectra of short tryptic peptides with
      leucine/isoleucine residues in neighboring positions demonstrate intensive w
      ions. On the contrary, u-ions possess very low intensities (if present at all).
      Therefore radical site migration is negligible in the applied conditions while
      ETD (EThcD) spectra allow for the reliable discrimination of the isomeric
      residues in the sequencing process. The presence of a fragment ion 43.055 mass
      units lower than z2-ion of peptides with IK sequence at their C-termini was shown
      to be a result of alternative fragmentation starting from the loss of
      propylammonium ion from the doubly protonated peptide molecule and formation of
      an oxazole fragment ion.

PMID- 29183200
TI  - Subsequent radical fragmentation reactions of N, N-diethylamino-substituted
      azobenzene derivatives in a Fourier transform ion cyclotron resonance mass
      spectrometer using collision-induced dissociation and photodissociation.
AB  - The fragmentation behavior of N, N-diethylamino-substituted azobenzene
      derivatives is investigated by high-resolving mass spectrometry using a Fourier
      transform ion cyclotron resonance mass spectrometer. Former investigations by
      photodissociation as well as collision-induced dissociation experiments used to
      induce a loss of C3H8 from the diethylamino group. The position of the additional
      proton in [M + H]+ ions is important due to the sequences of radical
      fragmentation reactions. Two possibilities arise. First, a charge is located at
      the azo group leading to a methyl radical loss. The second possibility is that
      the charge has been located on the aniline nitrogen of the molecule resulting in
      an ethyl radical loss. Only o-ethyl red has shown the overall loss of C3H8 in a
      two-step radical reaction mechanism. Nevertheless, p-ethyl red and ethyl yellow
      have shown systematic fragmentation reactions as well. Loss of C3H8 has not been
      likely regarding both these molecules. All experimental findings together with
      quantum chemical calculations as well as kinetic calculations support the
      proposed fragmentation mechanisms of the three azo dyes.

PMID- 29183201
TI  - Ripples on the surface. Surnames and genes in Sicily and Southern Italy.
AB  - BACKGROUND: Southern Italy and Sicily played a key role in the peopling history
      of the Mediterranean. While genetic research showed the remarkable homogeneity of
      these regions, surname-based studies instead suggested low population mobility,
      hence potential structuring. AIM: In order to better understand these different
      patterns, this study (1) thoroughly analysed the surname structure of Sicily and
      Southern Italy and (2) tested its relationships with a wide set of molecular
      markers. SUBJECTS AND METHODS: Surname data were collected from 1213
      municipalities and compared to uniparental and autosomal genetic markers typed in
      ~300 individuals from 8-10 populations. Surname analyses were performed using
      different multivariate methods, while comparisons with genetic data relied on
      correlation tests. RESULTS: Surnames were clearly structured according to
      regional geographic patterns, which likely emerged because of recent isolation-by
      distance-like population dynamics. In general, genetic markers, hinting at a
      pervasive homogeneity, did not correlate with surname distribution. However, long
      autosomal haplotypes (>5 cM) that compared to genotypic (SNPs) data identify more
      "recent" relatedness, showing a clear association with surname patterns.
      CONCLUSION: The apparent contradiction between surname structure and genetic
      homogeneity was resolved by figuring surnames as recent "ripples" deposited on a
      vast and ancient homogeneous genetic "surface".

PMID- 29183202
TI  - Outcome of children and adolescents with relapsed Hodgkin lymphoma treated with
      high-dose therapy and autologous stem cell transplantation: the Memorial Sloan
      Kettering Cancer Center experience.
AB  - To evaluate outcomes and prognostic markers among children with relapsed Hodgkin
      lymphoma (HL) treated with autologous stem cell transplant (ASCT), we conducted a
      retrospective analysis of 36 consecutive pediatric patients treated at Memorial
      Sloan Kettering Cancer Center from 1989 to 2013. With a median follow-up of 9.6
      years, the 10-year overall survival (OS) and event-free survival (EFS) were 74.1
      and 67.1% respectively. Absence of B-symptoms, chemotherapy-sensitive disease,
      and transplant date after 1997 were each associated with superior EFS [HR 0.12 (p
      = .0015), 0.18 (p = .0039), and 0.17 (p = .0208), respectively]. Childhood
      Hodgkin International Prognostic Score at relapse (R-CHIPS) was calculated in a
      subset of patients (n = 22) and a lower score was associated with improved OS (HR
      0.29, p = .0352) and a trend toward improved EFS (HR 0.38, p = .0527). In
      summary, ASCT results in durable remission for the majority of pediatric patients
      with relapsed HL. R-CHIPS should be evaluated in larger cohorts as a potential
      predictive tool.

PMID- 29183203
TI  - Assessing the diagnostic yield of controllable biopsy-forceps for biliary
      strictures.
AB  - OBJECTIVE: Biliary forceps biopsies are essential for differentially diagnosing
      biliary strictures and evaluating the preoperative superficial intraductal spread
      of bile duct cancers; however, these biopsies are technically demanding and time
      consuming. Using controllable biopsy-forceps (C-BF), which enable the tip's angle
      to be adjusted by up to 90 degrees , may facilitate the procedure and improve the
      diagnostic yield for biliary biopsies. This study aimed to examine the efficacy
      of C-BF associated with the diagnosis of biliary strictures. MATERIALS AND
      METHOD: Between 2009 and 2015, 110 patients with biliary strictures underwent
      biliary biopsies using C-BF. We retrospectively evaluated the diagnostic yield of
      C-BF for biliary strictures and determined the success rate associated with
      obtaining adequate samples during mapping biopsies to evaluate the superficial
      intraductal tumor spread. RESULTS: The technical success rate for biliary
      biopsies using C-BF was 99% (109/110). The sensitivity, specificity and accuracy
      of the diagnoses of biliary strictures were 60% (46/77), 100% (33/33) and 72%
      (79/110), respectively. Regarding the mapping biopsy procedures, adequate samples
      were successfully obtained from 96% (22/23), 92% (11/12), 80% (12/15), 75% (9/12)
      and 31% (5/16) of the intrapancreatic common bile ducts, upper common bile ducts,
      confluences of the hepatic ducts, right intrahepatic bile ducts and left
      intrahepatic bile ducts, respectively. CONCLUSIONS: C-BF may facilitate biliary
      cannulation and mapping biopsies of the common bile duct and the right
      intrahepatic bile duct. However, given that the diagnostic sensitivity was 60%,
      further modifications are expected and necessary to maximize the utility of the
      controllable mechanism.

PMID- 29183204
TI  - Diffuse Alveolar-Septal Amyloidosis Associated With Multiple Myeloma.

PMID- 29183206
TI  - Fibrates in the management of atherogenic dyslipidemia.
AB  - INTRODUCTION: Significant advancements in the treatment of hypercholesterolemia
      have recently been achieved. However, a considerable level of residual
      cardiovascular risk still affects patients' outcomes. Atherogenic dyslipidemia is
      one of the major constituents of residual risk. Fibrates, PPAR alpha agonists,
      which modify lipid profile and have numerous pleiotropic effects, seem to be
      drugs of choice in patients with atherogenic dyslipidemia. These drugs are
      effective both in monotherapy and combined therapy with statins. Areas covered: A
      review of clinical trials and experimental studies on fibrates and their use in
      the treatment of lipid disorders has been performed. Expert commentary: Fibrates
      are an effective and safe group of drugs to treat patients with atherogenic
      dyslipidemia. In this particular population of patients, they improve
      cardiovascular outcomes. Benefits of fibrate treatment extend beyond the impact
      of lipid profile. Significant improvements in carbohydrate metabolism, adipokines
      levels, thrombosis and inflammation were also noted.

PMID- 29183207
TI  - "I'm very visible but seldom seen": consumer choice and use of mobility aids on
      public transport.
AB  - PURPOSE: The number of mobility aid users continues to rise as the population
      ages. While mobility aid users rely on public transport due to its affordability,
      evidence suggests access can be difficult. This study aims to describe people who
      use mobility aids to access public transport and the role of public transport
      access in influencing mobility aid choice. METHODS: Sixty-seven mobility aid
      users participated in telephone surveys which predominantly used a structured
      quantitative format. Data were analysed descriptively and any additional comments
      were simply categorized. RESULTS: Thirty-six participants were female (54%), with
      a total sample mean age of 58.15 years (SD = 14.46). Seventy-two percent lived in
      metropolitan areas, 48% lived alone, and the sample experienced a variety of
      conditions including spinal cord injury (37%) and arthritis (18%). Sixty-four
      percent of all respondents used two or more mobility aids including powered
      wheelchairs, scooters and walking frames. The most important features when
      choosing a mobility aid were reliability, turning ability and size. Fifty-two
      percent of all respondents strongly agreed that public transport is generally
      accessible. CONCLUSIONS: While work continues to ensure that public transport
      vehicles and stations are fully accessible, mobility aid users must manage
      current infrastructure and access a system which has been shown through this
      research to have many limitations. Mobility aid users, vendors and health
      professionals need to work together to identify mobility aids that fulfil needs,
      and are reliable and safe, so that mobility aid users are both "visible and seen"
      when accessing the public transport network. Implications for rehabilitation Some
      mobility aid users experience difficulties accessing and using public transport
      and further research is required to ensure the whole public transport network is
      fully accessible to people using mobility aids. Many people have more than one
      seated mobility aid, suggesting people can choose different aids for different
      purposes and environments. Health professionals may need to increase their
      involvement in assisting individuals to select and use mobility aids.

PMID- 29183205
TI  - The elemental changes occurring in the rat liver after exposure to PEG-coated
      iron oxide nanoparticles: total reflection x-ray fluorescence (TXRF) spectroscopy
      study.
AB  - The main goal of this study was to evaluate in vivo effects of low dose of PEG
      coated magnetic iron oxide nanoparticles (IONPs) on the rat liver. The IONPs was
      intravenously injected into rats at a dose equaled to 0.03 mg of Fe per 1 kg of
      an animal body weight. The elemental composition of liver tissue in rats
      subjected to IONPs action and controls were compared. Moreover, in order to
      determine the dynamics of nanoparticles (NPs) induced elemental changes, the
      tissues taken from animals 2 hours, 24 hours, and 7 days from IONPs injection
      were examined. The analysis of subtle elemental anomalies occurring as a result
      of IONPs action required application of highly sensitive analytical method. The
      total reflection X-ray fluorescence spectroscopy perfectly meets such
      requirements and therefore it was used in this study. The obtained results showed
      increasing trend of Fe level within liver occurring 2 hours from IONPs injection.
      One day after NPs administration, the liver Fe content presented the baseline
      level what suggests only the short-term accumulation of nanoparticles in the
      organ. The Ca, Cu, and Zn levels changed significantly as a result of NPs action.
      Moreover, the anomalies in their accumulation were still observed 7 days after
      IONPs injection. The level of Cu decreased while those of Ca and Zn increased in
      the liver of NPs-treated animals. The reduced liver Cu, followed by elevated
      serum level of this element, might be related in triggering the mechanisms
      responsible for Fe metabolism in the organism.

PMID- 29183209
TI  - [CME - Transient Global Amnesia].
AB  - Transient global amnesia (TGA) is a neurological condition which is still a
      diagnostic challenge for clinicians. Diagnostic clues are an acute onset of a
      disturbance of memory, a lack of other focal neurological deficits, and
      repetitive questioning of the patients about time and circumstances. Although the
      signs and symptoms are quite typical, making the diagnosis of TGA might still be
      challenging, depending on the patient's characteristics. Taking a precise history
      from the patient and his/her next of kin is seminal. This article discusses the
      typical clinical presentation, pathophysiological hypotheses, the diagnostic
      clues and the most important differential diagnoses.

PMID- 29183208
TI  - S100B increases in cyanotic versus noncyanotic infants undergoing heart surgery
      and cardiopulmonary bypass (CPB).
AB  - AIMS: S100B has been proposed as a consolidated marker of brain damage in infants
      with congenital heart disease (CHD) undergoing cardiac surgery and
      cardiopulmonary bypass (CPB). The present study aimed to investigate whether
      S100B blood levels in the perioperative period differed in infants complicated or
      not by cyanotic CHD (CHDc) and correlated with oxygenation status (PaO2).
      METHODS: We conducted a case-control study of 48 CHD infants without pre-existing
      neurological disorders undergoing surgical repair and CPB. 24 infants were CHDc
      and 24 were CHD controls. Blood samples for S100B assessment were collected at
      six monitoring time-points: before the surgical procedure (T0), after sternotomy
      but before CPB (T1), at the end of the cross-clamp CPB phase (T2), at the end of
      CPB (T3), at the end of the surgical procedure (T4), at 24 h postsurgery (T5).
      RESULTS: In the CHDc group, S100B multiples of median (MoM) were significantly
      higher (p < .05, for all) from T0 to T5. PaO2 was significantly lower (p < .05,
      for all) in CHDc infants at T0-T1 and at T4 while no differences (p > .05, for
      all) were found at T2, T3, T5. Linear regression analysis showed a positive
      correlation between S100B MoM at T3 and PaO2 (R = 0.84; p < .001). CONCLUSIONS:
      The present data showing higher hypoxia/hyperoxia-mediated S100B concentrations
      in CHDc infants suggest that CHDc are more prone to perioperative brain
      stress/damage and suggest the usefulness of further investigations to detect the
      "optimal" PaO2 target in order to avoid the side effects associated with
      reoxygenation during CPB.

PMID- 29183210
TI  - ?

PMID- 29183211
TI  - ?

PMID- 29183212
TI  - ?

PMID- 29183213
TI  - ?

PMID- 29183215
TI  - ?

PMID- 29183214
TI  - ?

PMID- 29183216
TI  - [CME Rheumatology 13/Solution: Shoulder Pain, Muscle Weakness and Skin Rash].

PMID- 29183217
TI  - ?

PMID- 29183219
TI  - ?

PMID- 29183218
TI  - ?

PMID- 29183220
TI  - The effect of low volume sprint interval training in patients with non-alcoholic
      fatty liver disease.
AB  - OBJECTIVES: Exercise is an important part of disease management in patients with
      non-alcoholic fatty liver disease (NAFLD), but adherence to current exercise
      recommendations is poor. Novel low-volume sprint interval training (SIT)
      protocols with total training time commitments of <=30 min per week have been
      shown to improve cardiometabolic risk and functional capacity in healthy
      sedentary participants, but the efficacy of such protocols in the management of
      NAFLD remains unknown. The aim of the present study was to examine whether a low
      volume SIT protocol can be used to improve liver function, insulin resistance,
      body composition, physical fitness, cognitive function and general well-being in
      patients with NAFLD. METHODS: In the present study, 7 men and 2 women with NAFLD
      (age: 45 +/- 8 y, BMI: 28.7 +/- 4.1 kg.m-2) completed a 6-week control period
      followed by 6 weeks of twice-weekly SIT sessions (5-10 * 6-s 'all-out' cycle
      sprints). Body composition, blood pressure, liver function, metabolic function,
      functional capacity, cognitive function and quality of life were assessed at
      baseline, following the control period, and following the SIT intervention.
      RESULTS: Walking speed during the walk test (+12%), estimated VO2max (+8%),
      verbal fluency (+44%), and blood platelet count (+12%; all p < 0.05)
      significantly increased during the control period. These measures remained
      significantly raised compared to baseline following the SIT intervention, but did
      not significantly change any further compared to the post-control time-point.
      Diastolic blood pressure decreased from 87 +/- 10 to 77 +/- 8 mm Hg from the end
      of the control period to the end of the SIT intervention (p < 0.05). CONCLUSION:
      This study does not support the use of 6 weeks of a low volume SIT protocol
      involving twice-weekly sessions with 5-10 * 6-s 'all-out' cycle sprints as an
      intervention for NAFLD disease management.

PMID- 29183221
TI  - Duration of anticoagulant therapy in pediatric venous thromboembolism: Current
      approaches and updates from randomized controlled trials.
AB  - INTRODUCTION: Compared with the incidence of venous thromboembolism in the adult
      population, pediatric VTE is rare. Yet, recent data suggest that the incidence of
      VTE in children is increasing, and little is known about the optimal duration of
      anticoagulation in pediatrics. Areas covered: This review summarizes current
      evidence-based adult recommendations and associated clinical trials from which
      current guidelines on the duration of anticoagulation in children have been
      extrapolated. It also discusses pediatric expert consensus-based guidelines and
      current pediatric clinical trials on duration of therapy in pediatric VTE. Expert
      commentary: The vast majority of pediatric VTE are provoked, and evidence on
      duration of anticoagulation for pediatric VTE is highly limited, but suggests
      that a maximum duration of 3 months is reasonable for most patients with provoked
      VTE, whereas longer duration is likely appropriate for unprovoked VTE. Whether
      shorter duration than 3 months is optimal for pediatric provoked VTE is as yet
      unclear. Results from the multinational randomized controlled trial studying the
      duration of anticoagulant therapy for provoked VTE in patients <21 years old
      (Kids-DOTT) will be critical to inform the future standard of care in pediatric
      VTE treatment.

PMID- 29183222
TI  - The Lifetime of Salience Extends Beyond the Initial Saccade.
AB  - Several models of selection in search predict that saccades are biased toward
      conspicuous objects (also referred to as salient objects). Indeed, it has been
      demonstrated that initial saccades are biased toward the most conspicuous
      candidate. However, in a recent study, no such bias was found for the second
      saccade, and it was concluded that the attraction of conspicuous elements is
      limited to only short-latency initial saccades. This conclusion is based on only
      a single feature manipulation (orientation contrast) and conflicts with the
      prediction of influential salience models. Here, we investigate whether this
      result can be generalized beyond the domain of orientation. In displays
      containing three luminance annuli (Experiment 1), we find a considerable bias
      toward the most conspicuous candidate for the second saccade. In Experiment 1,
      the target could not be discriminated peripherally. When we made the target
      peripherally discriminable, the second saccade was no longer biased toward the
      more conspicuous candidate (Experiment 2). Thus, conspicuity plays a role in
      saccadic selection beyond the initial saccade. Whether second saccades are biased
      toward conspicuous objects appears to depend on the type of feature contrast
      underlying the conspicuity and the peripheral discriminability of target
      properties.

PMID- 29183224
TI  - Age-related changes in implicit emotion processing.
AB  - The aim of the present study was to compare the performance of older and younger
      adults on an emotional priming task. Moreover, a nonemotional priming paradigm
      was used as a control task to disentangle age-related changes due to emotional
      processing difficulties from modifications due to a decline of executive
      inhibitory control abilities. Twenty-two young and 22 older healthy participants
      completed an emotional priming task and a nonemotional priming task. In the older
      adult group, reaction times in the emotional priming paradigm were not influenced
      by any of the prime conditions, whereas both groups exhibited similar
      facilitation effects induced by the congruent prime in the nonemotional task. The
      selective lack of an emotional priming effect in older adults shown in this
      preliminary report suggests that aging-induced changes in the ability to
      recognize emotions implicitly are directly dependent on emotional processing
      difficulties and not due to a general age-related modification of cognitive
      processes.

PMID- 29183223
TI  - "Just as Canadian as Anyone Else"? Experiences of Second-Class Citizenship and
      the Mental Health of Young Immigrant and Refugee Men in Canada.
AB  - In recent years, the experiences of immigrant and refugee young men have drawn
      attention worldwide. Human-induced environmental disasters, local and global
      conflicts, and increasingly inequitable distributions of wealth have shaped
      transnational migration patterns. Canada is home to a large immigrant and refugee
      population, particularly in its urban areas, and supporting the mental health and
      well-being of these communities is of critical importance. The aim of this
      article is to report findings from a qualitative study on the social context of
      mental health among immigrant and refugee young men, with a focus on their
      migration and resettlement experiences. Informed by the conceptual lens of social
      context, a thematic narrative analysis approach was used to examine qualitative
      data from individual and group interviews with 33 young men (age 15 to 22 years)
      self-identified as immigrants or refugees and were living in Greater Vancouver,
      western Canada. Three thematic narratives were identified: a better life, living
      the (immigrant) dream, and starting again from way below. The narratives
      characterized the social context for immigrant and refugee young men and were
      connected by a central theme of negotiating second-class citizenship.
      Implications include the need for mental health frameworks that address
      marginalization and take into account the contexts and discourses that shape the
      mental health of immigrant and refugee populations in Canada and worldwide.

PMID- 29183225
TI  - Prospective memory functioning in individuals with Parkinson's disease: a
      systematic review.
AB  - Objective There is growing interest in investigating prospective memory (PM)
      functioning in individuals with Parkinson's disease (PD) without dementia because
      evidence suggests that PM may be impaired in this clinical population. This paper
      reviews current literature on PM functioning in PD patients with the aim of
      discussing (i) the potential contribution of executive and episodic memory
      disorders to PM impairments, (ii) whether PM impairment is an independent
      disorder in PD or whether it is a sign of mild cognitive impairment (MCI) and
      (iii) the efficacy of cognitive interventions in treating PM disorders in these
      patients. Method A search of the relevant literature revealed 21 original
      research papers and five review/meta-analyses that directly investigated PM
      abilities in PD samples. Results Analysis of the reported data revealed that both
      executive functions and episodic memory are involved in the PM performance of
      patients with PD. Moreover, sparse evidence suggests that PM is not impaired in
      all PD patients but, rather, that PM deficits may be specifically associated with
      MCI. Finally, preliminary findings suggest that cognitive interventions may be
      effective in improving PM functioning in PD patients with MCI who present a well
      established neuropsychological profile. Conclusions Although some shortcomings of
      the PM literature on PD patients prevent drawing firm conclusions, this review of
      current evidence highlights the importance of including PM assessment in the
      standard neuropsychological evaluation of patients with PD. Moreover, there are
      indications that ad hoc cognitive programs applied according to the qualitative
      cognitive profile of patients could improve their PM abilities.

PMID- 29183226
TI  - Analysis of follow-up at the diagnostic level in the Polish Universal Neonatal
      Hearing Screening Programme.
AB  - Objectives Routine analysis showed that between 1 June and 30 November 2014, only
      47.6% of expected follow-up visits at the diagnostic level were registered in the
      Polish Universal Neonatal Hearing Screening Programme central database. We
      attempted to detect and analyse the reasons for this low percentage. Methods A
      telephone survey questionnaire was developed for parents whose children had not
      registered for consultation at the diagnostic level, or had not received a final
      diagnosis according to the programme database. Questions aimed to verify the
      database records and compare these with information received from and given to
      parents. From the 7888 children not registered at the diagnostic level, 3239
      records were randomly selected, i.e. 52.4% of those who had been expected to
      attend. Results Questions were answered by 1950 parents (60.2% of the selected
      group). Of these, 52.1% ( n = 734) had attended for diagnostic tests, but this
      was not recorded in the database. The most common reasons for not attending were
      the long waiting time for the visit (36.09%), lack of referral to a visit (25.9%)
      and conscious parent decision (16.35%). Conclusion The telephone survey disclosed
      omissions in database registration, and that in fact 83.6% of children had
      attended at the diagnostic level.

PMID- 29183227
TI  - Malignant Mixed Germ Cell Tumor Overgrowing a Gonadoblastoma in a Female With a
      46, XX Karyotype: A Case Report.
AB  - Gonadoblastoma is an uncommon ovarian tumor arising primarily in females with
      gonadal dysgenesis and a 46, XY karyotype. Germ cell tumors arising within and/or
      overgrowing a gonadoblastoma have been reported. We report a rare case of a
      malignant mixed germ cell tumor (yolk sac tumor and choriocarcinoma) arising in a
      gonadoblastoma of the left ovary in a 19-year-old female with a 46, XX karyotype.
      The patient's initial alpha-fetoprotein level was 20 000 KIU/L. The patient
      underwent a laparoscopic unilateral salpingo-oophorectomy with omentectomy and
      peritoneal washing followed by adjuvant chemotherapy.

PMID- 29183228
TI  - Recommendations for buprenorphine and methadone therapy in opioid use disorder: a
      European consensus.
AB  - INTRODUCTION: Management of patients with opioid use disorder (OUD) commonly
      includes opioid agonist therapy (OAT) as a part of an integrated treatment plan.
      These interventions are associated with proven benefits to the individual and
      society. Areas covered: The use of methadone and buprenorphine within an
      integrated treatment plan in the management of patients with OUD: this work
      provides consensus recommendation on pharmacotherapy in OUD to assist clinicians
      with practical decision making in this field. Expert opinion: Pharmacotherapy is
      recommended as part of an integrated OUD treatment approach with psychosocial
      interventions, with the goal of reducing risks of illicit opioid use, overdose
      mortality, infection with HIV or HCV, improving health, psychological and social
      outcomes. Access to OAT should be prioritised in the treatment of OUD. Treatment
      choices in OUD pharmacotherapy should be based on the needs of the individual and
      characteristics of medications. Recommendations for choices of OAT are based on
      clinical efficacy, safety, patient preference, side effects, pharmacological
      interactions, quality of life, dose titration potential and outcomes (control
      craving, ongoing opioids consumption or other drugs, and potentially psychiatric
      comorbidities). Special groups, pregnant women, prisoners, patients with mental
      health problems have specific needs which must be addressed with expert input.

PMID- 29183229
TI  - Prevalence of sickle cell disease among Grenadian newborns.
AB  - Objective To establish the birth prevalence of sickle cell disease in Grenada,
      with a view to assess the requirement for a population-based neonatal screening
      programme. Methods A two-year pilot neonatal screening programme, involving the
      Ministry of Health of Grenada, the Sickle Cell Association of Grenada, and the
      diagnostic laboratory of hemoglobinopathies of the University Hospital of
      Guadeloupe, was implemented in 2014-2015 under the auspices of the Caribbean
      Network of Researchers on Sickle Cell Disease and Thalassemia. Results Analysis
      of 1914 samples processed identified the following abnormal phenotypes: 10 FS, 2
      FSC, 183 FAS, 63 FAC. These data indicate betas and betac allele frequencies of
      0.054 and 0.018, respectively. Conclusion Neonatal screening conducted in the
      framework of this Caribbean cooperation can allow rapid detection and earlier
      management of affected children.

PMID- 29183230
TI  - How good are publicly available web services that predict bioactivity profiles
      for drug repurposing?
AB  - Drug repurposing provides a non-laborious and less expensive way for finding new
      human medicines. Computational assessment of bioactivity profiles shed light on
      the hidden pharmacological potential of the launched drugs. Currently, several
      freely available computational tools are available via the Internet, which
      predict multitarget profiles of drug-like compounds. They are based on chemical
      similarity assessment (ChemProt, SuperPred, SEA, SwissTargetPrediction and
      TargetHunter) or machine learning methods (ChemProt and PASS). To compare their
      performance, this study has created two evaluation sets, consisting of (1) 50
      well-known repositioned drugs and (2) 12 drugs recently patented for new
      indications. In the first set, sensitivity values varied from 0.64 (TarPred) to
      1.00 (PASS Online) for the initial indications and from 0.64 (TarPred) to 0.98
      (PASS Online) for the repurposed indications. In the second set, sensitivity
      values varied from 0.08 (SuperPred) to 1.00 (PASS Online) for the initial
      indications and from 0.00 (SuperPred) to 1.00 (PASS Online) for the repurposed
      indications. Thus, this analysis demonstrated that the performance of machine
      learning methods surpassed those of chemical similarity assessments, particularly
      in the case of novel repurposed indications.

PMID- 29183231
TI  - In silico prediction of multiple-category classification model for cytochrome
      P450 inhibitors and non-inhibitors using machine-learning method.
AB  - The cytochrome P450 (CYP) enzyme superfamily is involved in phase I metabolism
      which chemically modifies a variety of substrates via oxidative reactions to make
      them more water-soluble and easier to eliminate. Inhibition of these enzymes
      leads to undesirable effects, including toxic drug accumulations and adverse drug
      drug interactions. Hence, it is necessary to develop in silico models that can
      predict the inhibition potential of compounds for different CYP isoforms. This
      study focused on five major CYP isoforms, including CYP1A2, 2C9, 2C19, 2D6 and
      3A4, that are responsible for more than 90% of the metabolism of clinical drugs.
      The main aim of this study is to develop a multiple-category classification model
      (MCM) for the major CYP isoforms using a Laplacian-modified naive Bayesian
      method. The dataset composed of more than 4500 compounds was collected from the
      PubChem Bioassay database. VolSurf+ descriptors and FCFP_8 fingerprint were used
      as input features to build classification models. The results demonstrated that
      the developed MCM using Laplacian-modified naive Bayesian method was successful
      in classifying inhibitors and non-inhibitors for each CYP isoform. Moreover, the
      accuracy, sensitivity and specificity values for both training and test sets were
      above 80% and also yielded satisfactory area under the receiver operating
      characteristic curve and Matthews correlation coefficient values.

PMID- 29183232
TI  - A QSAR and molecular modelling study towards new lead finding:
      polypharmacological approach to Mycobacterium tuberculosis.
AB  - Developing effective inhibitors against Mycobacterium tuberculosis (Mtb) is a
      challenging task, primarily due to the emergence of resistant strains. In this
      study, we have proposed and implemented an in silico guided polypharmacological
      approach, which is expected to be effective against resistant strains by
      simultaneously inhibiting several potential Mtb drug targets. A combination of
      pharmacophore and QSAR based virtual screening strategy taking three key targets
      such as InhA (enoyl-acyl-carrier-protein reductase), GlmU (N-acetyl-glucosamine-1
      phosphate uridyltransferase) and DapB (dihydrodipicolinate reductase) have
      resulted in initial 784 hits from Asinex database of 435,000 compounds. These
      hits were further subjected to docking with 33 Mtb druggable targets. About 110
      potential polypharmacological hits were taken by integrating the aforementioned
      screening protocols. Further screening was conducted by taking various parameters
      and properties such as cell permeability, drug-likeness, drug-induced
      phospholipidosisand structural alerts. A consensus analysis has yielded 59
      potential hits that pass through all the filters and can be prioritized for
      effective drug-resistant tuberculosis. This study proposes about nine potential
      hits which are expected to be promising molecules, having not only drug-like
      properties, but also being effective against multiple Mtb targets.

PMID- 29183233
TI  - Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor
      System.
AB  - The rate and oscillatory hypotheses are the two main current frameworks of basal
      ganglia pathophysiology. Both hypotheses have emerged from research on movement
      disorders sharing similar conceptualizations. These pathological conditions are
      classified either as hypokinetic or hyperkinetic, and the electrophysiological
      hallmarks of basal ganglia dysfunction are categorized as prokinetic or
      antikinetic. Although nonmotor symptoms, including neurobehavioral symptoms, are
      a key manifestation of basal ganglia dysfunction, they are uncommonly accounted
      for in these models. In patients with Parkinson's disease, the broad spectrum of
      motor symptoms and neurobehavioral symptoms challenges the concept that basal
      ganglia disorders can be classified into two categories. The profile of symptoms
      of basal ganglia dysfunction is best characterized by a breakdown of information
      processing, accompanied at an electrophysiological level by complex alterations
      of spiking activity from basal ganglia neurons. The authors argue that the
      dynamics of the basal ganglia circuit cannot be fully characterized by linear
      properties such as the firing rate or oscillatory activity. In fact, the neuronal
      spiking stream of the basal ganglia circuit is irregular but has temporal
      structure. In this context, entropy was introduced as a measure of probabilistic
      irregularity in the temporal organization of neuronal activity of the basal
      ganglia, giving place to the entropy hypothesis of basal ganglia pathology.
      Obtaining a quantitative characterization of irregularity of spike trains from
      basal ganglia neurons is key to elaborating a new framework of basal ganglia
      pathophysiology.

PMID- 29183234
TI  - Predictors of Workplace Disability in a Premanifest Huntington's Disease Cohort.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disease involving
      motor, cognitive, and psychiatric/behavioral impairments that will eventually
      affect work role functioning. Few objective data exist regarding predictors of
      workplace disability in HD. The authors explored the predictors of work
      impairment and disability in a cross-sectional cohort of 656 employed,
      premanifest HD (preHD) individuals. In this cohort-the majority of whom were
      female, urban-dwelling, married/partnered, and working full-time, with minimal
      cognitive impairment, good function, minimal motor abnormality, and no indication
      of significant mental health issues-the number of participants who reported that
      they had missed work due to HD was low (2.4%). However, 12% of the study sample
      reported experiencing impairment while working due to preHD, 12.2% reported work
      related activity impairment due to preHD, and 12.7% reported impairment in their
      overall work ability. Higher numbers of CAG repeats on the mutant allele and
      having more motor symptoms were associated with significantly higher odds of
      experiencing workplace impairment. Importantly, several modifiable factors were
      also found to predict workplace disability. Specifically, higher levels of
      anxiety symptoms were associated with significantly higher odds of experiencing
      workplace impairment. Good mental and physical health served as protective
      factors, where good physical health was associated with 6% lower odds of
      experiencing impairment or missing work time and good mental health was
      associated with of 10%-12% lower. The results provide important new knowledge for
      the development of future targeted intervention trials to support preHD
      individuals in maintaining their work roles as long as possible.

PMID- 29183235
TI  - Pneumococcal conjugate vaccine use for the prevention of pneumococcal disease in
      adults <50 years of age.
AB  - Introduction; Adults, particularly those with underlying chronic conditions, eg,
      cardiovascular, liver, and pulmonary diseases and diabetes mellitus, have a
      persistent pneumococcal disease burden. Thirteen-valent pneumococcal conjugate
      vaccine (PCV13) is recommended in the United States for all adults aged >=65
      years and immunocompromised adults aged <65 years to protect against vaccine
      serotype (VT) invasive pneumococcal disease (IPD) and pneumonia. PCV13 is not
      recommended for immunocompetent adults aged >=18 years with comorbidities
      associated with increased pneumococcal disease risk. Areas covered: This US
      focused review summarizes PCV13-type IPD and community-acquired pneumonia burden
      in adults aged <50 years, PCV13 immunogenicity and safety in this population, and
      adult pneumococcal vaccination recommendations. Expert commentary: Considering
      (i) PCV13 has demonstrated efficacy against VT-IPD and pneumonia in adults aged
      >=65 years (with or without underlying chronic conditions), and (ii) immune
      responses to PCV13 in younger adults are comparable or better than in older
      adults, PCV13 would likely have similar efficacy in adults aged <50 years.
      Recommending PCV13 for at-risk adults aged <50 years would provide direct
      immunologic benefit of a conjugate vaccine and could address an important unmet
      medical need for pneumococcal pneumonia prevention. Although not directly
      addressed here, this benefit would likely extend to at-risk adults aged 50-64
      years.

PMID- 29183236
TI  - The Controversy Surrounding the Treatment of Deltoid and Syndesmotic Injuries of
      the Ankle: Is There Any Consensus?

PMID- 29183238
TI  - Why do I get out of bed everyday?

PMID- 29183239
TI  - The Social Context of Driving Cessation: Understanding the Effects of Cessation
      on the Life Satisfaction of Older Drivers and Their Social Partners.
AB  - Older adults with vision loss and a friend or family member were interviewed over
      a 2-year period. We examined the effects of driving cessation on life
      satisfaction among older adults and a social contact. Drivers' use of public
      transportation was examined as a moderator. Driving cessation was associated with
      a decline in life satisfaction among social partners but not for the drivers.
      Drivers' use of public transportation at baseline moderated the effects of
      cessation on changes in well-being among social partners, but had little effect
      on the life satisfaction of the drivers. Life satisfaction was greater among the
      social partners of ex-drivers who used public transportation more frequently. The
      association between driving cessation and well-being should be studied in the
      context of older drivers' social networks. Infrastructure (e.g., subways and
      buses) that supports transportation needs plays an important role in mitigating
      the effects of cessation on older adults' social networks.

PMID- 29183240
TI  - Enhanced "Train and Hope" for Scalable, Cost-Effective Professional Development
      in Youth Suicide Prevention.
AB  - BACKGROUND: The knowledge base surrounding how to most effectively prepare and
      sustain practitioner knowledge and skills for suicide risk assessment and
      management is limited. AIMS: This study examined the impact of a 6-hr continuing
      education training, and the effect of a posttraining reminder system, on mental
      health practitioners' knowledge, attitudes, and behavior surrounding suicide
      assessment and intervention. METHOD: Data were obtained prior to the training,
      immediately after the training, and at the 3-month follow-up. Medical record data
      were abstracted for a subsample of practitioners. Participants were randomly
      assigned to an e-mail reminder condition or no reminder condition that provided
      information related to the training. RESULTS: All practitioners demonstrated
      increase s in suicide assessment knowledge and attitudes for engaging in suicide
      risk assessments from pre- to posttest, and gains were maintained at the 3-month
      follow-up. There was no effect of the e-mail reminder on practitioner knowledge,
      attitudes, or behaviors compared with the condition without the e-mail reminder.
      The use of e-mail reminders was not associated with any additional changes.
      LIMITATIONS: Limitations include predominantly self-report and small sample.
      CONCLUSION: Strategies to effectively change practitioner knowledge, attitudes,
      and behaviors toward suicidal clients may include continuing education. Efficient
      and effective designs of reminder systems for augmenting and supporting suicide
      assessment management training are needed.

PMID- 29183241
TI  - Alcohol Involvement in Suicide and Self-Harm.
AB  - BACKGROUND: Alcohol misuse and alcohol consumption are significant risk factors
      for suicidal behavior. AIMS: This study sought to identify factors associated
      with alcohol consumption in cases of suicide and nonfatal self-harm
      presentations. METHOD: Suicide cases in Cork, Ireland, from September 2008 to
      June 2012 were identified through the Suicide Support and Information System.
      Emergency department presentations of self-harm in the years 2007-2013 were
      obtained from the National Self-Harm Registry Ireland. RESULTS: Alcohol
      consumption was detected in the toxicology of 44% out of 307 suicide cases. Only
      younger age was significantly associated with having consumed alcohol among
      suicides. Alcohol consumption was noted in the case notes in 21% out of 8,145
      self-harm presentations. Logistic regression analyses indicated that variables
      associated with having consumed alcohol in a self-harm presentation included male
      gender, older age, overdose as a method, not being admitted to a psychiatric
      ward, and presenting out-of-hours. LIMITATIONS: Data was limited to routinely
      collected variables by the two different monitoring systems. CONCLUSION: Alcohol
      consumption commonly precedes suicidal behavior, and several factors
      differentiated alcohol-related suicidal acts. Self-harm cases, in particular,
      differ in profile when alcohol is consumed and may require a tailored clinical
      approach to minimize risk of further nonfatal or fatal self-harm.

PMID- 29183242
TI  - Blurred Boundaries - A Qualitative Study of How Acts of Self-Harm and Attempted
      Suicide Are Defined by Mental Health Practitioners.
AB  - BACKGROUND: There is no commonly accepted definition of the term self-harm, and
      there is an ongoing debate about whether or not it should include acts of
      attempted suicide. The use of this language in clinical practice has not
      previously been explored. AIMS: To investigate if, and how, practitioners
      distinguish between acts of self-harm and attempted suicide, and present any
      implications for practice. METHOD: We conducted semistructured interviews with a
      random sample of 18 frontline practitioners from 10 mental health wards and
      completed a thematic analysis of interview data. RESULTS: Most participants
      described self-harm and attempted suicide as distinct behaviors. Characteristics
      of the act, disclosures of intent, and the level of distress observed were
      commonly used to differentiate between self-harm and attempted suicide. Very few
      participants believed that people who self-harm may also feel suicidal.
      Practitioners confidently described two different behaviors, yet self-harm and
      attempted suicide were often conflated, revealing the challenges and complexities
      associated with the separation of these acts in clinical practice. LIMITATIONS:
      Clinicians working in other settings or disciplines may have different views.
      Participants' accounts may not be an accurate representation of what happens in
      practice. CONCLUSION: This study adds to a body of evidence which argues against
      the dichotomous separation of these behaviors into acts of suicidal and
      nonsuicidal self-harm.Our findings suggest there is no common understanding of
      the boundaries between self-harm and attempted suicide among frontline
      clinicians. The language currently used, and consequent practice, particularly
      with regard to risk assessment, is problematic. Efforts should be made to
      operationalize terms around suicidal behavior and to incorporate these into
      training for clinical staff.

PMID- 29183243
TI  - Telephone Crisis Support Workers' Intentions to Use Recommended Skills While
      Experiencing Functional Impairment.
AB  - BACKGROUND: Empathic engagement with distressed others can lead to elevated
      symptoms of psychological distress and functional impairment, which preclude
      helping professionals' delivery of optimal patient care. Whether telephone crisis
      support workers are impacted in a similar way is not currently reported in the
      literature. AIMS: This study examined the relationship between functional
      impairment and intentions to use recommended support skills in a representative
      national sample of 210 telephone crisis support workers. METHOD: Participants
      completed an online survey including measures of functional impairment and
      intentions to use recommended telephone crisis support skills with callers
      reporting suicidal ideation, symptoms of depression, and anxiety. RESULTS: As a
      group, participants who experienced greater functional impairment during the past
      month reported significantly lower intentions to use recommended support skills
      with callers than those who reported lower functional impairment. LIMITATIONS:
      Future research is needed to clarify the extent to which results generalize to
      telephone crisis support workers from other organizations. CONCLUSION: Results
      warrant further research to (a) identify determinants of telephone crisis support
      workers' functional impairment, and (b) for the deliberate management of
      telephone crisis support workers' functional impairment through developing and/or
      modifying existing service strategies to optimize workers' psychological well
      being and delivery of support to callers.

PMID- 29183244
TI  - Sodium butyrate enhances intestinal integrity, inhibits mast cell activation,
      inflammatory mediator production and JNK signaling pathway in weaned pigs.
AB  - The present study aimed to investigate the effects of sodium butyrate on the
      intestinal barrier and mast cell activation, as well as inflammatory mediator
      production, and determine whether mitogen-activated protein kinase signaling
      pathways are involved in these processes. A total of 72 piglets, weaned at 28 +/-
      1 d age, were allotted to two dietary treatments (control vs. 450 mg/kg sodium
      butyrate) for 2 wk. The results showed that supplemental sodium butyrate
      increased daily gain, improved intestinal morphology, as indicated by greater
      villus height and villus height:crypt depth ratio, and intestinal barrier
      function reflected by increased transepithelial electrical resistance and
      decreased paracellular flux of dextran (4 kDa). Moreover, sodium butyrate reduced
      the percentage of degranulated mast cells and its inflammatory mediator content
      (histamine, tryptase, TNF-alpha and IL-6) in the jejunum mucosa. Sodium butyrate
      also decreased the expression of mast cell-specific tryptase, TNF-alpha and IL-6
      mRNA. Sodium butyrate significantly decreased the phosphorylated ratio of JNK
      whereas not affecting the phosphorylated ratios of ERK and p38. The results
      indicated that the protective effects of sodium butyrate on intestinal integrity
      were closely related to inhibition of mast cell activation and inflammatory
      mediator production, and that the JNK signaling pathway was likely involved in
      this process.

PMID- 29183245
TI  - Variation in Practice Pattern of Male Hypogonadism: A Comparative Analysis of
      Primary Care, Urology, Endocrinology, and HIV Specialists.
AB  - The objective of the current study was to measure the adherence of guideline
      based evaluation and treatment of hypogonadism by medical specialty. A
      retrospective review was performed analyzing patients from a single academic
      institution within the past 10 years. The cohort of 193 men was grouped according
      to medical specialty of the diagnosing physician (50 urology, 49 primary care, 44
      endocrinology, and 50 HIV medicine). Adherence to guidelines was assessed using
      the Endocrine Society's criteria. Primary care patients were older compared to
      the rest of the cohort ( p < .001) but BMI and cardiovascular risk factors were
      similar ( p = .900). Patients treated by urologists and endocrinologists had the
      highest percentage of low testosterone findings at initial encounter at 72% ( p <
      .001). Sixty-two percent of urology patients had low LH or FSH compared to 63.6%
      for endocrinology and 16% for primary care ( p < .001). As for brain MRI
      findings, no urology patients had positive findings (0/9) while eight pituitary
      adenomas (40%) were found by endocrinologists. Forty-five percent of men treated
      by urologists received TRT without repeat confirmation, compared to 58% of
      endocrinologists, 77% of primary care, and 88% of HIV medicine ( p < .001). All
      urology patients had PSA checked before TRT compared to 77.5% of primary care and
      61.2% of endocrinology patients ( p = .063). Adherence to the guidelines helps
      prevent undue over-diagnosis and over-treatment of hypogonadism. This study
      suggests that adherence to guideline-based screening is varied among specialties.

PMID- 29183246
TI  - Uptake trends in the Scottish Bowel Screening Programme and the influences of
      age, sex, and deprivation.
AB  - Objective Age, sex, and deprivation are known factors influencing colorectal
      (bowel) cancer screening uptake. We investigated the influence of these factors
      on uptake over time. Methods Data from the Scottish Bowel Screening Programme
      (SBoSP) were collected between 2007 and 2014. End-points for analysis were
      uptake, faecal occult blood test positivity, and disease detection, adjusted for
      age, sex, deprivation, and year of screening. Results From 5,308,336 individual
      screening episodes documented, uptake gradually increased with increasing age up
      to 65-69 and was lower in men than women (52.4% vs. 58.7%, respectively).
      Deprivation had a significant effect on uptake by men and women of all age
      groups, with the most deprived least likely to complete a screening test. Uptake
      has increased with time in both sexes and across the deprivation gradient. The
      number needed to screen to detect significant neoplasia was significantly lower
      in men than women overall (170 vs. 365), and this held over all age and
      deprivation groups. The number needed to screen was also lower in the more
      deprived population. Conclusions Although lower age, male sex, and increased
      deprivation are associated with lower bowel cancer screening uptake in Scotland,
      uptake has increased since SBoSP introduction in all age groups, both sexes, and
      across the deprivation gradient. Despite a lower uptake, the number needed to
      screen to find significant disease was lower in men and in those with higher
      levels of deprivation.

PMID- 29183247
TI  - Is the devil in the detail? Evidence for S-S learning after unconditional
      stimulus revaluation in human evaluative conditioning under a broader set of
      experimental conditions.
AB  - Whether valence change during evaluative conditioning is mediated by a link
      between the conditional stimulus (CS) and the unconditional stimulus (US; S-S
      learning) or between the CS and the unconditional response (S-R learning) is a
      matter of continued debate. Changing the valence of the US after conditioning,
      known as US revaluation, can be used to dissociate these accounts. Changes in CS
      valence after US revaluation provide evidence for S-S learning but if CS valence
      does not change, evidence for S-R learning is found. Support for S-S learning has
      been provided by most past revaluation studies, but typically the CS and US have
      been from the same stimulus category, the task instructions have suggested that
      judgements of the CS should be based on the US, and USs have been mildly valenced
      stimuli. These factors may bias the results in favour of S-S learning. We
      examined whether S-R learning would be evident when CSs and USs were taken from
      different categories, the task instructions were removed, and more salient USs
      were used. US revaluation was found to influence explicit US evaluations and
      explicit and implicit CS evaluations, supporting an S-S learning account and
      suggesting that past results are stable across procedural changes.

PMID- 29183248
TI  - Assessing the landscape of percutaneous coronary chronic total occlusion
      treatment in Belgium and Luxembourg: the Belgian Working Group on Chronic Total
      Occlusions (BWGCTO) registry.
AB  - BACKGROUND: Important developments in materials, devices, and techniques have
      improved outcomes of chronic total occlusion (CTO) percutaneous coronary
      intervention (PCI), and resulted in a growing interest in CTO-PCI. The Belgian
      Working Group on Chronic Total Occlusions (BWGCTO) working group aims to assess
      the evolution within the CTO-PCI landscape over the next years. METHODS: From May
      2016 onwards, patients undergoing CTO-PCI were included in the BWGCTO registry by
      15 centres in Belgium and Luxemburg. Baseline, angiographic, and procedural data
      were collected. Here, we report on the one-year in-hospital outcomes. RESULTS:
      Over the course of one year, 411 procedures in 388 patients were included with a
      mean age of 64 +/- 11 years. The majority were male (81%). Relatively complex
      CTOs were treated (Japanese CTO score =2.2 +/- 1.2) with a high procedure success
      rate (82%). Patient- and lesion-wise success rates were 83 and 85%, respectively.
      Major adverse in-hospital events were acceptably low (3.4%). Antegrade wire
      escalation technique was applied most frequently (82%). On the other hand,
      antegrade dissection and re-entry and retrograde strategies were more frequently
      applied in higher volume centres and successful for lesions with higher
      complexity. CONCLUSION: Satisfactory procedural outcomes and a low rate of
      adverse events were obtained in a complex CTO population, treated by operators
      with variable experience levels. Antegrade wire escalation was the preferred
      strategy, regardless of operator volume.

PMID- 29183249
TI  - Truth-telling, decision-making, and ethics among cancer patients in nursing
      practice in China.
AB  - BACKGROUND: Truth-telling toward terminally ill patients is a challenging ethical
      issue in healthcare practice. However, there are no existing ethical guidelines
      or frameworks provided for Chinese nurses in relation to decision-making on truth
      telling of terminal illness and the role of nurses thus is not explicit when
      encountering this issue. OBJECTIVES: The intention of this paper is to provide
      ethical guidelines or strategies with regards to decision-making on truth-telling
      of terminal illness for Chinese nurses. METHODS: This paper initially present a
      case scenario and then critically discuss the ethical issue in association with
      ethical principles and philosophical theories. Instead of focusing on attitudes
      toward truth disclosure, it aims to provide strategies regarding this issue for
      nurses. It highlights and discusses some of the relevant ethical assumptions
      around the perceived role of nurses in healthcare settings by focusing on nursing
      ethical virtues, nursing codes of ethics, and philosophical perspectives. And
      Confucian culture is discussed to explicate that deontology does not consider
      family-oriented care in China. CONCLUSION: Treating each family individually to
      explore the family's beliefs and values on this issue is essential in healthcare
      practice and nurses should tailor their own approach to individual needs
      regarding truth-telling in different situations. Moreover, the Chinese Code of
      Ethics should be modified to be more specific and applicable. Finally, a
      narrative ethics approach should be applied and teamwork between nurses,
      physicians and families should be established to support cancer patients and to
      ensure their autonomy and hope. Ethical considerations: This paper was approved
      by the Ethics Committee of The Second Affiliated Hospital of Guangzhou Medical
      University. The authors have obtained consent to use the case study and it has
      been anonymised to preserve the patient's confidentiality.

PMID- 29183250
TI  - Internalized stigma in people with severe mental illness in rural China.
AB  - BACKGROUND: It is unknown whether there are differences in self-stigma among
      persons with different types of severe mental illness (SMI) in rural communities.
      AIM: This study was to examine the differences of self-stigma and its correlates
      in persons with schizophrenia, major depressive disorder or bipolar disorder in a
      rural community in China. METHODS: A total of 453 persons with schizophrenia,
      major depressive disorder or bipolar disorder in a rural community participated
      in the study. The Internalized Stigma of Mental Illness (ISMI) was used to
      measure self-stigma. The t-test and analyses of variance (ANOVA) were used to
      examine the differences in mean scores of ISMI and subscales among the three
      diagnoses. Logistic regression was used to explore the contributing factors to
      the level of self-stigma among the three groups. RESULTS: Self-stigma was
      moderate and severe with 94.7% of the total sample. Persons with schizophrenia
      had significantly higher mean scores of total ISMI, alienation and discrimination
      experience than those with bipolar disorders. Lower family income was
      significantly associated with higher levels of self-stigma in persons with
      schizophrenia and major depressive disorder. Factors predicting the level of self
      stigma among the three groups were various. CONCLUSION: Self-stigma is common and
      severe in persons with schizophrenia, major depressive disorder and bipolar
      disorder, especially those with lower income status in rural community in China.
      Persons with schizophrenia may have higher levels of self-stigma than those with
      bipolar disorder. Individual-level interventions should be developed to reduce
      self-stigma among persons with SMI in Chinese rural communities.

PMID- 29183251
TI  - Promoting Postpartum Mental Health in Fathers: Recommendations for Nurse
      Practitioners.
AB  - The transition to fatherhood can challenge the mental health of first-time
      fathers and heighten their risk for postpartum depression (PPD). Paternal PPD not
      only affects the individual, but relationships with partners and children as
      well. This scoping review explores paternal PPD, highlighting the factors for and
      impacts of paternal PPD, the experiences of first-time fathers during the
      postnatal period, including their knowledge gaps and learning preferences.
      Drawing on the scoping review findings, recommendations are made for postnatal
      programs to improve the inclusion of new fathers amid describing how nurse
      practitioners can promote men's mental health in the postpartum period.

PMID- 29183252
TI  - Sexual Dysfunction in a Patient Taking Ledipasvir/Sofosbuvir for the Treatment of
      Hepatitis C: A Case Report.
AB  - Sexual dysfunction is a bothersome side effect of several medications, though it
      has not yet been reported with the use of ledipasvir/sofosbuvir for the treatment
      of hepatitis C. However, sexual dysfunction is a potentially unrecognized side
      effect of ledipasvir/sofosbuvir that could result in nonadherence and treatment
      failure. We report a case of a 42-year-old man with a sudden onset of sexual
      dysfunction with the initiation of ledipasvir/sofosbuvir for the treatment of
      hepatitis C. The patient had no prior history or risk factors for the development
      of sexual dysfunction. His symptoms resolved upon discontinuation of
      ledipasvir/sofosbuvir after a successful 12-week course. Clinicians should be
      aware that sexual dysfunction is a possible side effect of ledipasvir/sofosbuvir
      and educate patients appropriately. Adherence should be emphasized as the risks
      of untreated hepatitis C virus far outweigh transient sexual dysfunction.

PMID- 29183253
TI  - Implementation of a Cardiac Transitions of Care Pilot Program: A Prospective
      Study of Inpatient and Outpatient Clinical Pharmacy Services for Patients With
      Heart Failure Exacerbation or Acute Myocardial Infarction.
AB  - BACKGROUND: Pharmacists may assist with reducing 30-day readmission rates for
      patients with heart failure (HF) exacerbation or acute myocardial infarction
      (AMI) by promoting medication adherence. OBJECTIVE: To determine the change in 30
      day readmission rates for patients with HF exacerbation or AMI after
      implementation of a "high-touch" standard of care. METHODS: Patients admitted
      with HF exacerbation, non-ST-segment elevation AMI, or ST-segment elevation AMI
      from August 1, 2013, to June 30, 2015, were included in this prospective study.
      Patients were educated while in the inpatient setting and followed up in the
      outpatient setting through telephone contact and scheduling a medication therapy
      management (MTM) appointment with a pharmacist. Data were collected by pharmacy
      personnel involved in the implementation of the intervention. RESULTS: Within the
      HF and AMI arms, 100 and 93 patients, respectively, were included in the study.
      The 30-day readmission rates were 24% and 17.2% for HF and AMI, respectively,
      which were not statistically significant when compared to historical
      institutional readmission rates prior to study initiation (18.2% for HF, P =
      .238; 11.4% for AMI, P = .252). CONCLUSION: A "high-touch" pharmacist-driven
      transitions of care program may affect 30-day readmission rates for patients with
      HF exacerbation or AMI; potential processes for initiating transitions of care
      programs are provided.

PMID- 29183254
TI  - Feasibility study on the use of thiosulfate to remediate mercury-contaminated
      soil.
AB  - The feasibility of using sodium thiosulfate to remediate the mercury-contaminated
      soil around a local chemical plant in northeastern China has been investigated.
      Effects of solid-to-reagent ratio and temperature on mercury extraction from soil
      samples with thiosulfate solutions were examined. BCR (European Community Bureau
      of Reference) analysis indicated that more than 90% of weak acid soluble and
      reducible mercury in the soil sample could be extracted by thiosulfate solution.
      Mercury extraction kinetics can be described by the two-step first-order reaction
      model in which the readily extractable fraction and the less extractable fraction
      of mercury were associated with their own rate constants. Mercury extraction with
      thiosulfate solutions could be slightly promoted when the contaminated soil was
      pre-oxidized with hydrogen peroxide. The results suggest that thiosulfate is a
      potentially effective complexing lixiviant in mercury-contaminated soil
      remediation.

PMID- 29183255
TI  - Suckling in litters with different sizes, and early and late swimming exercise
      differentially modulates anxiety-like behavior, memory and electrocorticogram
      potentiation after spreading depression in rats.
AB  - OBJECTIVE: Analyze the hypothesis that swimming exercise, in rats suckled under
      distinct litter sizes, alters behavioral parameters suggestive of anxiety and
      recognition memory, and the electrocorticogram potentiation that occurs after the
      excitability-related phenomenon that is known as cortical spreading depression
      (CSD). METHODS: Male Wistar rats were suckled in litters with six or 12 pups (L6
      and L12 groups). Animals swam at postnatal days (P) 8-23, or P60-P75 (early
      exercised or late-exercised groups, respectively), or remained no-exercised.
      Behavioral tests (open field - OF and object recognition - OR) were conducted
      between P77 and P80. Between P90 and P120, ECoG was recorded for 2 hours. After
      this 'baseline' recording, CSD was elicited every 30 minutes over the course of 2
      hours. RESULTS: Early swimming enhanced the number of entries and the percentage
      of time in the OF-center (P < 0.05). In animals that swam later, this effect
      occurred in the L6 group only. Compared to the corresponding sedentary groups, OR
      test showed a better memory in the L6 early exercised rats, and a worse memory in
      all other groups (P < 0.05). In comparison to baseline values, ECoG amplitudes
      after CSD increased 14-43% for all groups (P < 0.05). In the L6 condition, early
      swimming and late swimming, respectively, reduced and enhanced the magnitude of
      the post-CSD ECoG potentiation in comparison with the corresponding L6 no
      exercised groups (P < 0.05). DISCUSSION: Our data suggest a differential effect
      of early- and late-exercise on the behavioral and electrophysiological
      parameters, suggesting an interaction between the age of exercise and the
      nutritional status during lactation.

PMID- 29183256
TI  - Experimental and Mathematical Analyses Relating Circadian Period and Phase of
      Entrainment in Neurospora crassa.
AB  - Circadian rhythms are observed in most organisms on earth and are known to play a
      major role in successful adaptation to the 24-h cycling environment. Circadian
      phenotypes are characterized by a free-running period that is observed in
      constant conditions and an entrained phase that is observed in cyclic conditions.
      Thus, the relationship between the free-running period and phase of entrainment
      is of interest. A popular simple rule has been that the entrained phase is the
      expression of the period in a cycling environment (i.e., that a short period
      causes an advanced phase and a long period causes a delayed phase). However,
      there are experimental data that are not explained by this simple relationship,
      and no systematic study has been done to explore all possible period-phase
      relationships. Here, we show the existence of stable period-phase relationships
      that are exceptions to this rule. First, we analyzed period-phase relationships
      using populations with different degrees of genome complexity. Second, we
      generated isogenic F1 populations by crossing 14 classical period mutants to the
      same female and analyzed 2 populations with a short period/delayed phase and a
      long period/advanced phase. Third, we generated a mathematical model to account
      for such variable relationships between period and phase. Our analyses support
      the view that the circadian period of an organism is not the only predictor of
      the entrained phase.

PMID- 29183257
TI  - Sodium bicarbonate improves 4 km time trial cycling performance when
      individualised to time to peak blood bicarbonate in trained male cyclists.
AB  - The aim of this study was to investigate the effects of sodium bicarbonate
      (NaHCO3) on 4 km cycling time trial (TT) performance when individualised to a
      predetermined time to peak blood bicarbonate (HCO3-). Eleven male trained
      cyclists volunteered for this study (height 1.82 +/- 0.80 m, body mass (BM) 86.4
      +/- 12.9 kg, age 32 +/- 9 years, peak power output (PPO) 382 +/- 22 W). Two
      trials were initially conducted to identify time to peak HCO3- following both 0.2
      g.kg-1 BM (SBC2) and 0.3 g.kg-1 BM (SBC3) NaHCO3. Thereafter, on three separate
      occasions using a randomised, double-blind, crossover design, participants
      completed a 4 km TT following ingestion of either SBC2, SBC3, or a taste-matched
      placebo (PLA) containing 0.07 g.kg-1 BM sodium chloride (NaCl) at the
      predetermined individual time to peak HCO3-. Both SBC2 (-8.3 +/- 3.5 s; p <
      0.001, d = 0.64) and SBC3 (-8.6 +/- 5.4 s; p = 0.003, d = 0.66) reduced the time
      to complete the 4 km TT, with no difference between SBC conditions (mean
      difference = 0.2 +/- 0.2 s; p = 0.87, d = 0.02). These findings suggest trained
      cyclists may benefit from individualising NaHCO3 ingestion to time to peak HCO3-
      to enhance 4 km TT performance.

PMID- 29183259
TI  - Advances in endometrial cancer protein biomarkers for use in the clinic.
AB  - INTRODUCTION: Endometrial cancer (EC) is the fourth most common cancer in women
      in developed countries. The identification of sensitive and specific biomarkers
      to improve early detection of EC is crucial for an appropriate management of this
      disease, in which 30% of patients are diagnosed only at advanced stages, which is
      associated with high levels of morbidity and mortality. Despite major efforts and
      investments made to identify EC biomarkers, no protein has yet reached the stage
      of clinical application. Areas covered: This review gathers the numerous
      candidate biomarkers for EC diagnosis proposed in proteomic studies published
      from 1978 to 2017. Additionally, we summarize limitations associated with the
      proteomic technologies and study designs employed in those articles. Finally, we
      address new perspectives in EC biomarker research, including the comprehensive
      knowledge of previously suggested candidate biomarkers in conjunction with novel
      mass spectrometry-based proteomic technologies with enhanced sensitivity and
      specificity not yet applied to EC studies and a directed clinical perspective in
      the study design. Expert commentary: These ingredients could be the recipe to
      accelerate the application of protein biomarkers in the clinic.

PMID- 29183258
TI  - [Transitional and Adolescent Psychiatry in Austria: A Pilot Study on the
      Attitudes of Experts].
AB  - : Transitional and Adolescent Psychiatry in Austria: A Pilot Study on the
      Attitudes of Experts Abstract. OBJECTIVE: This pilot study establishes baseline
      data on the current situation of transitional processes in Austrian psychiatry.
      We sought to gather information on the specific problems and needs occurring
      during the transition of mentally ill adolescents from child and adolescent to
      adult psychiatry. METHOD: Professionals (psychiatrists, psychologists,
      psychotherapists) working in child and adolescent psychiatry and adult psychiatry
      (N = 86) were assessed by means of an online survey concerning their experience
      with the transition of young adults. RESULTS: Almost all of the subjects queried
      (98.8 %) considered the current system inappropriate, and the majority (70.9 %)
      thought that patients would not tolerate transition from youth to adult
      psychiatric institutions very well. Only 16.3 % reported having a structured
      transition protocol at their workplace. Further 83.7 % expressed the need to
      improve collaboration between adolescent and adult psychiatry. CONCLUSIONS: This
      sample of Austrian healthcare professionals describes large deficits regarding
      transitional issues in psychiatry. There is an urgent need to establish
      structured protocols for transition, especially since experiences occurring
      during this vulnerable period are crucial to the mental health of young people
      later in life.

PMID- 29183260
TI  - Vital statistics and early death predictors of North American professional
      basketball players: A historical examination.
AB  - While empirical evidence suggests that elite athletes have superior lifespan
      outcomes relative to the general population, less is known regarding their causes
      of death. The purpose of this study was to critically examine the mortality
      outcomes of deceased National Basketball Association and American Basketball
      Association players. Death data were collected from publicly available sources
      until 11 December 2015, and causes of death were categorized using the
      International Classification of Diseases, Tenth Revision (ICD). Mortality was
      measured through: i) cause-specific crude death rates (CDR), ii) estimates of
      death rates per athlete-year (AY), and iii) binary and multinomial regression
      analyses. We identified 514 causes of death from 787 deceased players (M = 68.1 y
      +/- 16.0) from 16 different ICD groups, 432 of which were from natural causes.
      Findings showed similar leading causes of death and CDRs to sex- and race-matched
      controls, higher death rate differences per AY within time-dependent variables
      (i.e., birth decade, race, and height), and a higher likelihood of dying below
      the median age of death for black and taller players, although this was highly
      confounded by birth decade. More complete knowledge of mortality outcomes would
      provide broad public health applications and disarm harmful stereotypes of elite
      athlete health.

PMID- 29183261
TI  - Self-Reported Participation in Sport/Exercise Among Adolescents and Young Adults
      With and Without Mild to Moderate Intellectual Disability.
AB  - BACKGROUND: Physical inactivity is a leading risk factor for mortality. Adults
      with intellectual disability are extremely inactive, but less is known about
      physical activity levels in children and youth with intellectual disability. This
      paper examines the participation by adolescents and young adults with and without
      mild to moderate intellectual disability in sport/exercise. METHODS: Secondary
      analysis was undertaken of Next Steps, an annual panel study that followed a
      cohort from early adolescence into adulthood. Participants with mild to moderate
      intellectual disability were identified through data linkage with educational
      records. RESULTS: Sport/exercise participation rates were consistently lower for
      adolescents and young people with mild to moderate intellectual disability than
      for their peers without intellectual disability. Matching participants on between
      group differences in exposure to extraneous risk factors did not impact on these
      between-group differences in participation in sport/exercise. CONCLUSION: The
      results support limited existing evidence regarding the low level of
      participation of children and young people with intellectual disability in
      sport/exercise compared with their peers. Future work on promoting sport/exercise
      and physical activity in children and young people with intellectual disability
      may play a role in helping to reduce the health inequalities experienced by
      people with intellectual disability.

PMID- 29183262
TI  - Globus Symptoms in Patients Undergoing Thyroidectomy: Relationships with
      Psychogenic Factors, Thyroid Disease, and Surgical Procedure.
AB  - BACKGROUND: The number of patients who need thyroid surgery has increased
      worldwide in recent decades. Patients with thyroid disease experience globus
      pharyngeus as a result of direct compression and edema of the surrounding organs.
      Thyroid surgery is needed to improve these symptoms or as treatment for thyroid
      cancer. After thyroid surgery, globus symptoms may become worse and may affect
      the daily life of the patient for a long time. Psychogenic problems have also
      been thought to cause the globus sensation. A prospective analysis of globus
      symptoms and psychogenic factors following thyroidectomy was performed. MATERIAL
      AND METHODS: Patients scheduled to undergo thyroid surgery between February and
      September 2016 completed the foreign-body sensation in the throat score (FBST;
      range 0-8.2) and the self-rating depression scale (SDS; range 0-100)
      preoperatively and three days, one month, three months, six months, and 12 months
      postoperatively. RESULTS: Long-term follow-up was completed in 616 patients (491
      females). A total of 365 patients had thyroid cancer, 169 had benign tumors, and
      82 had diffuse goiters with Graves' disease. The percentage of patients who
      complained about neck discomfort (FBST >2) was 29.4% before surgery. A
      preoperative high FBST showed a significant direct correlation with a high SDS,
      but thyroid volume did not. A postoperative high FBST was seen in 75.3% of
      patients at two days and 78.9% at one month after surgery, and it then gradually
      decreased to 49.3% at 12 months after surgery. At three days after the operation,
      the median FBST was significantly higher in patients who had total thyroidectomy
      with lateral neck dissection or total thyroidectomy only compared to those who
      had lobectomy only (p < 0.05). These differences were still present 12 months
      after surgery. A higher preoperative SDS score was also identified as an
      independent predictor for a high FBST at 12 months after surgery, but not at one
      or three months postoperatively, on multivariate analyses. CONCLUSION:
      Preoperative globus symptoms appear directly related to psychological factors.
      The area of the surgical procedure and preoperative psychological factors were
      related to persistent neck discomfort.

PMID- 29183263
TI  - Inverse European Latitudinal Cline at the timeless Locus of Drosophila
      melanogaster Reveals Selection on a Clock Gene: Population Genetics of ls-tim.
AB  - The spread of adaptive genetic variants in populations is a cornerstone of
      evolutionary theory but with relatively few biologically well-understood
      examples. Previous work on the ls-tim variant of timeless, which encodes the
      light-sensitive circadian regulator in Drosophila melanogaster, suggests that it
      may have originated in southeastern Italy. Flies characterized by the new allele
      show photoperiod-related phenotypes likely to be adaptive in seasonal
      environments. ls-tim may be spreading from its point of origin in Italy by
      directional selection, but there are alternative explanations for its observed
      clinal geographical distribution, including balancing selection and demography.
      From population analyses of ls-tim frequencies collected on the eastern side of
      the Iberian Peninsula, we show that ls-tim frequencies are inverted compared with
      those in Italy. This pattern is consistent with a scenario of directional
      selection rather than latitude-associated balancing selection. Neutrality tests
      further reveal the signature of directional selection at the ls-tim site, which
      is reduced a few kb pairs either side of ls-tim. A reanalysis of allele
      frequencies from a large number of microsatellite loci do not demonstrate any
      frequent ls-tim-like spatial patterns, so a general demographic effect or
      population expansion from southeastern Italy cannot readily explain current ls
      tim frequencies. Finally, a revised estimate of the age of ls-tim allele using
      linkage disequilibrium and coalescent-based approaches reveals that it may be
      only 300 to 3000 years old, perhaps explaining why it has not yet gone to
      fixation. ls-tim thus provides a rare temporal snapshot of a new allele that has
      come under selection before it reaches equilibrium.

PMID- 29183264
TI  - Qualitative analysis of the capacity to consent to treatment in patients with a
      chronic neurodegenerative disease: Alzheimer's disease / Analisi qualitativa
      sulla capacita a prestare consenso al trattamento in pazienti con malattie
      cronico degenerative neuropsicoorganiche: Demenza di Alzheimer.
AB  - OBJECTIVE: Informed consent is an essential element in doctor-patient
      relationship. In particular, obtaining valid informed consent from patients with
      neurocognitive diseases is a critical issue at present. For this reason, we
      decided to conduct research on elderly patients with Alzheimer's disease (
      Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) to
      assess their capacity to make treatment decisions. METHODS: The experimental
      group comprised 70 Alzheimer patients who were admitted to the Neurodegenerative
      Disease Unit of the University of Bari. The control group consisted of 83 elderly
      patients without neurocognitive disorders who were hospitalized in the Geriatric
      Unit at the same university. After providing written consent to participate in
      the research, each subject underwent the following assessments: (a) assessment of
      comprehension sheet, (b) Neuropsychiatric Inventory (NPI) and Global Functioning
      Evaluation (GFE), (c) neurological evaluation, (d) neuropsychological assessment
      with a full battery of tests, (d) The MacArthur Treatment Competence Study
      (MacArthur Competence Assessment Tool for Treatment (MacCAT-T); understanding,
      appreciating, reasoning and expressing a choice) and (e) a semi-structured
      interview administered by the patient's caregiver. RESULTS/CONCLUSION: The
      present survey was designed to analyze possible qualitative and quantitative
      correlations between cognitive functioning and capacity to consent in relation to
      different degrees of severity of the neurodegenerative disorder. A large portion
      of the patients in our experimental sample did not appear to have the capacity to
      provide a valid consent. The authors present initial results of this study and
      discuss their possible implications.

PMID- 29183265
TI  - When general practitioners meet new evidence: an exploratory ethnographic study.
AB  - OBJECTIVE: To explore how general practitioners (GPs) think and act when
      presented with new evidence in relation to planned home birth and a proposal to
      change information practices. DESIGN: Exploratory ethnographic study of GPs. The
      GPs were encountered one or more times during a two-year period, 2011-2013, while
      the author tried to set up formal focus group interviews. Dialogues about the
      evidence, personal experiences, values and other issues unavoidably occurred.
      Field notes were written concomitantly. SETTING: Danish GPs, primarily in
      Copenhagen. SUBJECTS: Fifty Danish GPs. RESULTS: The GPs reacted very
      differently, both spontaneously and later. Spontaneous reactions were often
      emotional involving private and professional experiences whereas later reactions
      were more influenced by rational deliberations. Approximately half the GPs (n =
      18) who were asked whether they would personally hand out the local information
      leaflet about home birth were prepared to do so. The time lag between
      presentation of the evidence and the GPs' decision to hand out the leaflets was
      up to one and a half year. CONCLUSIONS: A significant number of GPs were prepared
      to change their information practices. However, for many GPs, the new evidence
      challenged previous perceptions, and ample time and resources for dialogue,
      deliberations and adaptation to local circumstances were required to accommodate
      change. IMPLICATIONS: Changing information practices on a larger scale will
      require a systematic approach involving key stakeholders. Key Points Current
      awareness*Patients and pregnant women should receive evidence-based information
      about possible choices of care - also in relation to place of birth. Most
      important results*Doctors often find the new evidence supporting planned home
      birth counterintuitive and spontaneously react emotionally rather than rationally
      to the evidence.*The new evidence challenging previous views elicits fast,
      emotional reactions, later deliberate reflections, perhaps cognitive dissonance
      and, finally, for some, change in clinical practice. Significance for the
      readers*The findings may be applicable to other fields where an evidence-based
      choice between an interventionist and a conservative approach is relevant.

PMID- 29183266
TI  - Faecal immunochemical tests for the diagnosis of symptomatic colorectal cancer in
      primary care: the benefit of more than one sample.
AB  - OBJECTIVE: Faecal immunochemical tests (FITs) are used to screen for colorectal
      cancer (CRC) and as diagnostic aids in symptomatic patients. However, the number
      of samples per FIT varies. It is unclear if there is any advantage to analyse
      multiple-sample FITs in symptomatic patients. DESIGN AND SETTING: This is a post
      hoc analysis of a retrospective study that included all cases of CRC and adenomas
      with high-grade dysplasia (HGD) between 2005 and 2009 in the county of Jamtland,
      Sweden. SUBJECTS: All patients with CRC and adenomas with HGD that initially
      presented with symptoms to primary care and delivered FITs. MAIN OUTCOME MEASURE:
      The likelihood of a positive FIT in cases of CRC and adenomas with HGD; when
      analysing one, two or three samples. RESULTS: Of 195 patients, 160 delivered
      three-sample FITs. Using the 139 cases in which at least one sample was positive,
      the likelihood of detecting a positive sample upon analysis of only one of the
      three samples was 0.91 (95% CI: 0.85-0.95), indicating that 13 positive cases may
      have been missed. CONCLUSION: Use of a one-sample FIT instead of a three-sample
      FIT as a diagnostic aid may result in the missing of one tenth of symptomatic
      CRCs and adenomas with HGD.

PMID- 29183267
TI  - In silico evaluation of the resistance of the T790M variant of epidermal growth
      factor receptor kinase to cancer drug Erlotinib.
AB  - Epidermal growth factor receptor kinase is implicated in cancer development due
      to either overexpression or activation variants in its functional intracellular
      kinase domain. Threonine to methionine (Thr 790 Met) is one such variant observed
      commonly in patients showing resistance to kinase inhibitor drug Erlotinib. Two
      mechanisms for resistance have been proposed (1) steric hindrance and (2)
      enhanced binding to ATP. In this study, we employed molecular dynamics
      simulations and studied both the mechanisms. Extensive simulations and free
      energy of binding analyses has shown that steric hindrance does not explain
      appropriately the mechanism for resistance against Erlotinib therapy for this
      variant. It has been observed that conformational switching from an intermediate
      intrinsically disordered C-helix conformation is required for completion of the
      kinase's catalytic cycle. Our study substantiates that T790M variant has greater
      tendency for early transition to this intrinsically disordered C-helix
      intermediate state. We propose that enhanced catalytic efficiency in addition to
      enhanced ATP binding explains mechanism of T790M resistance to drug Erlotinib.

PMID- 29183268
TI  - Potential natural mTOR inhibitors screened by in silico approach and suppress
      hepatic stellate cells activation.
AB  - The mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase,
      plays a central role in the regulation of cell proliferation, growth,
      differentiation, migration, and survival. In this study, the 3-D structure of the
      mTOR (PDB ID: 2FAP) was used for the docking of 47 natural compounds and compared
      with pharmacophore model of 14 known mTOR inhibitors to identify the novel and
      specific natural inhibitor. The top four compounds, rutin, curcumin,
      antroquinonol, and benzyl cinnamate, have been selected based on their PLP score
      and further validated with hepatic stellate cells NHSC and THSC. Curcumin and
      antroquinonol significantly inhibited NHSC and THSC cells proliferation in a dose
      dependent manner, whereas rutin and benzyl cinnamate showed less alteration of
      cell viability. Rutin inhibited the phosphorylation of mTOR (p-mTOR) and p-p70 S6
      K in NHSC and THSC cells by Western blotting. Additionally, p-p70 S6 K protein
      was significantly decreased by incubation with benzyl cinnamate and curcumin in
      THSC cells. Taken together, this result suggests that rutin is a potential mTOR
      inhibitor in screen hits of molecular docking to hamper the activation of HSC and
      further applications in the treatment of liver fibrosis.

PMID- 29183269
TI  - High incidence of extra-genital gonorrheal and chlamydial infections among high
      risk men who have sex with men and transgender women in Peru.
AB  - Extra-genital Neisseria gonorrhoeae and Chlamydia trachomatis infections are
      associated with antimicrobial resistance and HIV acquisition. We analyzed data
      from a cohort of men who have sex with men (MSM) and transgender women followed
      quarterly for two years in Peru. Incident cases were defined as positive N.
      gonorrhoeae or C. trachomatis nucleic acid tests during follow-up. Repeat
      positive tests were defined as reinfection among those with documented treatment.
      We used generalized estimating equations to calculate adjusted incidence rate
      ratios (aIRRs). Of 404 participants, 22% were transgender. Incidence rates of
      rectal N. gonorrhoeae and C. trachomatis infection were 28.1 and 37.3 cases per
      100 person-years, respectively. Incidence rates of pharyngeal N. gonorrhoeae and
      C. trachomatis infection were 21.3 and 9.6 cases per 100 person-years,
      respectively. Incident HIV infection was associated with incident rectal (aIRR =
      2.43; 95% CI 1.66-3.55) N. gonorrhoeae infection. Identifying as transgender
      versus cisgender MSM was associated with incident pharyngeal N. gonorrhoeae (aIRR
      = 1.85; 95% CI 1.12-3.07) infection. The incidence of extra-genital N.
      gonorrhoeae and C. trachomatis infections was high in our population. The
      association with incident HIV infection warrants evaluating the impact of rectal
      N. gonorrhoeae screening and treatment on HIV transmission.

PMID- 29183270
TI  - Results from the post-exposure prophylaxis pilot program (P-QUAD) demonstration
      project in Los Angeles County.
AB  - Post-exposure prophylaxis (PEP) is a promising but under-utilized strategy for
      HIV prevention in high-risk populations. Between March 2010 and June 2011, two
      community-based clinics in Los Angeles County provided PEP in a pilot program to
      267 unique individuals. Courses were primarily dispensed to men who have sex with
      men (84%) and consisted overwhelmingly of a three-drug antiretroviral therapy
      regimen containing two nucleoside reverse transcriptase inhibitors and either an
      integrase inhibitor (raltegravir) or a boosted protease inhibitor
      (lopinavir/ritonavir). Approximately 64% of all PEP courses were followed for at
      least 12 weeks, and seven individuals seroconverted. Of the seven
      seroconversions, six had subsequent re-exposure. The low rate of PEP failure
      calls for expanded funding for PEP in other jurisdictions.

PMID- 29183271
TI  - Compulsory licensing of pharmaceuticals reconsidered: Current situation and
      implications for access to medicines.
AB  - To examine patterns and trends in attempts, distinguished from issuance, to issue
      compulsory licensing of pharmaceuticals and to assess related implications in the
      era of high-cost medicines. Documents from various civil society organisations
      were primarily used to search attempts, as well as published literature. The
      identified attempts were analysed by pharmaceutical level, national level,
      claimers, and the outcomes of the attempts. There have been 108 attempts to issue
      compulsory licensing for 40 pharmaceuticals in 27 countries since 1995. Most of
      the attempts were in Asian, Latin American, and African countries and mainly for
      HIV/AIDS medicines. Moreover, when the claimer was the government, the likelihood
      of approval and positive outcomes increased. Compulsory licensing, which was
      devised to cope with the HIV/AIDS pandemic in low-income countries, became a
      practical measure in several Asian and Latin American countries, even for non
      HIV/AIDS medicines. Resurgent compulsory licensing in 2012 and 2014, influenced
      by the global justice movement, might represent a policy window in the near
      future as the Doha Declaration did in the 2000s. In this context, various
      experiences should be circulated and analysed at the global level to better
      understand the circumstances under which successful issuance has been achieved at
      the country level.

PMID- 29183272
TI  - Efficacy and safety of additional surgery after non-curative endoscopic
      submucosal dissection for early colorectal cancer.
AB  - BACKGROUND: Additional surgery is recommended when early colorectal cancer (ECRC)
      is resected by non-curative endoscopic submucosal dissection (ESD) and there is
      significant risk of lymph node metastasis (LNM). The aim of this study was to
      investigate the efficacy and safety of additional surgery after non-curative ESD
      for ECRC and evaluate long-term outcomes. METHODS: Patients with ECRC who
      underwent ESD and additional surgery between July 2007 and November 2013 were
      identified. Histology and patient data were collected during an average period of
      more than 5 years to determine tumor stage and type, resection status,
      complications, tumor recurrence, and distant metastasis. RESULTS: Fifty-one
      patients who underwent additional surgery were eligible for analysis. Overall,
      regional LNM was detected in 5 patients (9.8%) and presence of lymphovascular
      infiltration was a significant risk factor. Surgery-related complications
      occurred in 3 patients (5.9%). During a median follow-up period of 59 months, no
      metastasis or local recurrence was observed. Three patients died of other
      diseases and no CRC-related deaths took place. CONCLUSIONS: Additional surgery
      after non-curative ESD for ECRC is effective and safe and should be encouraged to
      foster curative treatment and better long-term outcomes.

PMID- 29183273
TI  - Impact of the estimation equation for GFR on population-based prevalence
      estimates of kidney dysfunction.
AB  - BACKGROUND: Estimating equations are recommended by clinical guidelines as the
      preferred method for assessment of glomerular filtration rate (GFR). The aim of
      the study was to compare population-based prevalence estimates of decreased
      kidney function in Germany defined by an estimated GFR (eGFR) <60 ml/min/1.73m2
      using different equations. METHODS: The study included 7001 participants of the
      German Health Interview and Examination Survey for Adults 2008-2011 (DEGS1) for
      whom GFR was estimated using the Modification of Diet in Renal Disease study
      equation (MDRD), the revised Lund-Malmo equation (LM), the Full Age Spectrum
      creatinine equation (FAScre), the Chronic Kidney Disease Epidemiology
      Collaboration equations with creatinine and cystatin C (CKD-EPIcrecys), with
      creatinine (CKD-EPIcre) and with cystatin C (CKD-EPIcys). Bland-Altman plots were
      used to evaluate the agreement between the equations. RESULTS: Prevalence
      estimates of decreased kidney function were: 2.1% (CKD-EPIcys), 2.3% (CKD
      EPIcrecys), 3.8% (CKD-EPIcre), 5.0% (MDRD), 6.0% (LM) and 6.9% (FAScre). The
      systematic differences between the equations were smaller by comparing either
      equations that include serum cystatin C or equations that include serum
      creatinine alone and increased considerably by increasing eGFR. CONCLUSIONS:
      Prevalence estimates of decreased kidney function vary considerably according to
      the equation used for estimating GFR. Equations that include serum cystatin C
      provide lower prevalence estimates if compared with equations based on serum
      creatinine alone. However, the analysis of the agreement between the equations
      according to eGFR provides evidence that the equations may be used
      interchangeably among persons with pronounced decreased kidney function. The
      study illustrates the implications of the choice of the estimating equation in an
      epidemiological setting.

PMID- 29183274
TI  - Mortality trends for accidental falls in older people in Spain, 2000-2015.
AB  - BACKGROUND: Accidental falls in older people are a major public health problem
      but a relatively limited number of studies have analyzed the mortality trends
      from this cause. Effective public health interventions have been found to prevent
      the incidence of falls and their complications. Therefore, characterizing the
      mortality trends of falls for different subpopulations can help to identify their
      needs and contribute to develop more appropriate prevention programs for specific
      target groups. METHODS: This study was based on a longitudinal analysis of death
      rates from accidental falls (2000-2015) stratified by sex for the population >=
      65 years and by age groups (65-74, 75-84, >=85). A joinpoint regression model was
      used to identify trend inflection points. The Annual Percent Change (APC) was
      estimated for each trend. RESULTS: Mortality rates per 100,000 person-years
      increased from 20.6 to 30.1 for men and 13.8 to 20.8 for women between 2000 and
      2015. Men presented a relevant trend increase between 2008 and 2015 (APC [95% CI]
      7.2% [5.3;9.2]) and women between 2008 and 2013 (7.9% [4.1;11.8]) There were no
      trend differences between sexes. For 65-74 years old men we found a relevant
      increase in the last period (2011-2015) (7.8% [1.0;15.1]). Those aged 75-84 years
      showed a trend increase between 2007 and 2015 (6.4% [4.4;8.4]) and men >=85 years
      presented a remarkably high trend between 2008 and 2015 (9.0% [5.2;13]). There
      were no relevant differences between age groups. Women aged 65-74 had no relevant
      trend through the period. Those aged 75-84 presented an uniform trend increase
      for the whole period, 2000-2015, (3.4% [2.3;4.4]) and women >=85 had and
      important trend increase between 2008 and 2013 (11.1% [5.3;17.2]), that has
      reached an stable level in the last 2 years. There were no relevant differences
      between the 75-84 and >=85 age groups. CONCLUSIONS: Recent mortality trends from
      accidental falls increased in men >=65 years and women >=75 years. These results
      recommend the implementation of specific preventive programs.

PMID- 29183275
TI  - Prevalence and associated risk factors of undercorrected refractive errors among
      people with diabetes in Shanghai.
AB  - BACKGROUND: To investigate the prevalence and risk factors of undercorrected
      refractive error (URE) among people with diabetes in the Baoshan District of
      Shanghai, where data for undercorrected refractive error are limited. METHODS:
      The study was a population-based survey of 649 persons (aged 60 years or older)
      with diabetes in Baoshan, Shanghai in 2009. One copy of the questionnaire was
      completed for each subject. Examinations included a standardized refraction and
      measurement of presenting and best-corrected visual acuity (BCVA), tonometry,
      slit lamp biomicroscopy, and fundus photography. RESULTS: The calculated age
      standardized prevalence rate of URE was 16.63% (95% confidence interval [CI]
      13.76-19.49). For visual impairment subjects (presenting vision worse than 20/40
      in the better eye), the prevalence of URE was up to 61.11%, and 75.93% of
      subjects could achieve visual acuity improvement by at least one line using
      appropriate spectacles. Under multiple logistic regression analysis, older age,
      female gender, non-farmer, increasing degree of myopia, lens opacities status,
      diabetic retinopathy (DR), body mass index (BMI) index lower than normal, and
      poor glycaemic control were associated with higher URE levels. Wearing distance
      eyeglasses was a protective factor for URE. CONCLUSION: The undercorrected
      refractive error in diabetic adults was high in Shanghai. Health education and
      regular refractive assessment are needed for diabetic adults. Persons with
      diabetes should be more aware that poor vision is often correctable, especially
      for those with risk factors.

PMID- 29183276
TI  - The effectiveness of prehospital hypertonic saline for hypotensive trauma
      patients: a systematic review and meta-analysis.
AB  - BACKGROUND: The optimal prehospital fluid for the treatment of hypotension is
      unknown. Hypertonic fluids may increase circulatory volume and mute the pro
      inflammatory response of the body to injury and illness. The purpose of this
      systematic review is to determine whether in patients presenting with hypotension
      in the prehospital setting (population), the administration of hypertonic saline
      (intervention), compared to an isotonic fluid (control), improves survival to
      hospital discharge (outcome). METHODS: Searches were conducted in Medline,
      Embase, CINAHL, and CENTRAL from the date of database inception to November,
      2016, and included all languages. Two reviewers independently selected randomized
      control trials of hypotensive human participants administered hypertonic saline
      in the prehospital setting. The comparison was isotonic fluid, which included
      normal saline, and near isotonic fluids such as Ringer's Lactate. Assessment of
      study quality was done using the Cochrane Collaborations' risk of bias tool and a
      fixed effect meta-analysis was conducted to determine the pooled relative risk of
      survival to hospital discharge. Secondary outcomes were reported for fluid
      requirements, multi-organ failure, adverse events, length of hospital stay, long
      term survival and disability. RESULTS: Of the 1160 non-duplicate citations
      screened, thirty-eight articles underwent full-text review, and five trials were
      included in the systematic review. All studies administered a fixed 250 ml dose
      of 7.5% hypertonic saline, except one that administered 300 ml. Two studies used
      normal saline, two Ringer's Lactate, and one Ringer's Acetate as control. Routine
      care co-interventions included isotonic fluids and colloids. Five studies were
      included in the meta-analysis (n = 1162 injured patients) with minimal
      statistical heterogeneity (I 2  = 0%). The pooled relative risk of survival to
      hospital discharge with hypertonic saline was 1.02 times that of patients who
      received isotonic fluids (95% Confidence Interval: 0.95, 1.10). There were no
      consistent statistically significant differences in secondary outcomes.
      CONCLUSIONS: There was no significant difference in important clinical outcomes
      for hypotensive injured patients administered hypertonic saline compared to
      isotonic fluid in the prehospital setting. Hypertonic saline cannot be
      recommended for use in prehospital clinical practice for the management of
      hypotensive injured patients based on the available data. PROSPERO registration #
      CRD42016053385 .

PMID- 29183277
TI  - Unfavorable impact of cancer cachexia on activity of daily living and need for
      inpatient care in elderly patients with advanced non-small-cell lung cancer in
      Japan: a prospective longitudinal observational study.
AB  - BACKGROUND: Cancer cachexia in elderly patients may substantially impact physical
      function and medical dependency. The aim of this study was to estimate the impact
      of cachexia on activity of daily living (ADL), length of hospital stay, and
      inpatient medical costs among elderly patients with advanced non-small-cell lung
      cancer (NSCLC) receiving chemotherapy. METHODS: Thirty patients aged >=70 years
      with advanced NSCLC (stage III-IV) scheduled to receive first-line chemotherapy
      were prospectively enrolled between January 2013 and November 2014. ADL was
      assessed using the Barthel index. The disability-free survival time (DFS) was
      calculated as the time between the date of study entry and the date of onset of a
      disabling event, which was defined as a 10-point decrease in the Barthel index
      from that at baseline. The mean cumulative function of the length of hospital
      stay and inpatient medical costs (Y, Japanese yen) was calculated. RESULTS: The
      study patients comprised 11 women and 19 men, with a median age of 74 (range, 70
      82) years. Cachexia was diagnosed in 19 (63%) patients. Cachectic patients had a
      shorter DFS (7.5 vs. 17.1 months, p < 0.05). During the first year from study
      entry, cachectic patients had longer cumulative lengths of hospital stay (80.7
      vs. 38.5 days/person, p < 0.05), more frequent unplanned hospital visits or
      hospitalizations (4.2 vs. 1.7 times/person, p < 0.05), and higher inpatient
      medical costs (Y3.5 vs. Y2.1 million/person, p < 0.05) than non-cachectic
      patients. CONCLUSIONS: Elderly NSCLC patients with cachexia showed higher risks
      for disability, prolonged hospitalizations, and higher inpatient medical costs
      while receiving chemotherapy than patients without cachexia. Our results might
      indicate that there is a potential need for an early intervention to minimize
      progression to or development of cachexia, improve functional prognosis, and
      reduce healthcare resource burden in this population. TRIAL REGISTRATION: Trial
      registration number: UMIN000009768 . Name of registry: UMIN (University hospital
      Medical Information Network). Date of registration: 14 January 2013. Date of
      enrolment of the first participant to the trial: 23 January 2013.

PMID- 29183278
TI  - Capnography sensor use is associated with reduction of adverse outcomes during
      gastrointestinal endoscopic procedures with sedation administration.
AB  - BACKGROUND: Evidence to date suggests that capnography monitoring during
      gastrointestinal endoscopic procedures (GEP) reduces the incidence of hypoxemia,
      but the association of capnography monitoring with the incidence of other adverse
      outcomes surrounding these procedures has not been well studied. Our aims were to
      estimate the incidence of pharmacological rescue events and death at discharge
      from an inpatient or outpatient hospitalization where GEP was performed with
      sedation, and to determine if capnography monitoring was associated with reduced
      incidence of these adverse outcomes. METHODS: This retrospective Premier Database
      analysis included medical inpatients and all outpatients undergoing GEP with
      sedation. Patients were grouped as follows: (1) pulse oximetry (SpO2) only, (2)
      capnography only, (3) SpO2 with capnography, and (4) neither SpO2 nor
      capnography. Multivariable logistic regression and propensity-score matching were
      used to compare patients with capnography sensor use to patients with only SpO2
      sensor use. Outcome measures included the incidence of pharmacological rescue
      events, as defined by administration of naloxone and/or flumazenil, and death.
      RESULTS: Two hundred fifty eight thousand and two hundred sixty two inpatients
      and 3,807,151 outpatients were analyzed. For inpatients, capnography monitoring
      was associated with a 47% estimated reduction in the odds of death at discharge
      (OR: 0.53 [95% CI: 0.40-0.70]; P < 0.0001) and a non-significant 10% estimated
      reduction in the odds of pharmacological rescue event at discharge (0.91 [0.65
      1.3]; P = 0.5661). For outpatients, capnography monitoring was associated with a
      61% estimated reduction in the odds of pharmacological rescue event at discharge
      (0.39 [0.29, 0.52]; P < 0.0001) and a non-significant 82% estimated reduction in
      the odds of death at discharge (0.18 [0.02, 1.99]; P = 0.16). CONCLUSIONS: In
      hospital medical inpatients and all outpatients undergoing GEP performed with
      sedation, capnography monitoring was associated with a reduced likelihood of
      pharmacological rescue events in outpatients and death in inpatients when
      assessed at discharge. Despite the limitations of the retrospective data analysis
      methodology, the use of capnography during these procedures is recommended.

PMID- 29183279
TI  - Panitumumab use in metastatic colorectal cancer and patterns of RAS testing:
      results from a Europe-wide physician survey and medical records review.
AB  - BACKGROUND: In Europe, treatment of metastatic colorectal cancer (mCRC) with
      panitumumab requires prior confirmation of RAS wild-type mutation status. Two
      studies - a physician survey and a medical records review (MRR) - were conducted
      to evaluate the use of panitumumab and awareness among prescribing oncologists of
      the associated RAS testing requirements in clinical practice. METHODS: Both
      studies enrolled participants from nine European countries and were carried out
      in three consecutive rounds. Rounds 1 and 2 (2012-2013) examined KRAS (exon 2)
      testing only; the results have been published in full previously. Round 3 (2014
      2015) examined full RAS testing (exons 2, 3, 4 of KRAS and NRAS) and was
      initiated following a change in prescribing guidelines, from requiring KRAS alone
      to requiring full RAS testing. For the physician survey, telephone interviews
      were conducted with oncologists who had prescribed panitumumab to patients with
      mCRC in the previous 6 months. For the MRR, oncologists were asked to provide
      anonymised clinical information, extracted from their patients' records. RESULTS:
      In Round 3, 152 oncologists and 131 patients' records were included in the
      physician survey and MRR, respectively. In Round 3 of the physician survey, 95.4%
      (n = 145) of participants correctly identified that panitumumab should only be
      prescribed in RAS wild-type mCRC compared with 99.0% (n = 298) of 301
      participants in Rounds 1 and 2, responding to the same question about KRAS
      testing. In Round 3 of the MRR, 100% (n = 131) of patients included in the study
      had confirmed KRAS or RAS wild-type status prior to initiation of panitumumab
      compared with 97.7% (n = 299) of 306 patients in Rounds 1 and 2 (KRAS only). Of
      those patients in Round 3, 83.2% (n = 109) had been tested for RAS status and
      16.8% (n = 22) had been tested for KRAS status only. CONCLUSIONS: Physicians'
      adherence to prescribing guidelines has remained high over time in Europe,
      despite the change in indication for panitumumab treatment, from KRAS to RAS wild
      type mCRC. Additionally, this study demonstrates the uptake of full RAS testing
      among the majority of oncologists and pathologists.

PMID- 29183280
TI  - Using a monitoring and evaluation framework to improve study efficiency and
      quality during a prospective cohort study in infants receiving rotavirus
      vaccination in El Alto, Bolivia: the Infant Nutrition, Inflammation, and
      Diarrheal Illness (NIDI) study.
AB  - BACKGROUND: Implementing rigorous epidemiologic studies in low-resource settings
      involves challenges in participant recruitment and follow-up (e.g., mobile
      populations, distrust), biological sample collection (e.g., cold-chain,
      laboratory equipment scarcity) and data collection (e.g., literacy, staff
      training, and infrastructure). This article describes the use of a monitoring and
      evaluation (M&E) framework to improve study efficiency and quality during
      participant engagement, and biological sample and data collection in a
      longitudinal cohort study of Bolivian infants. METHODS: The study occurred
      between 2013 and 2015 in El Alto, Bolivia, a high-altitude, urban, low-resource
      community. The study's M&E framework included indicators for participant
      engagement (e.g., recruitment, retention, safety), biological sample (e.g., stool
      and blood), and data (e.g., anthropometry, questionnaires) collection and
      quality. Monitoring indicators were measured regularly throughout the study and
      used for course correction, communication, and staff retraining. RESULTS:
      Participant engagement indicators suggested that enrollment objectives were met
      (461 infants), but 15% loss-to-follow-up resulted in only 364 infants completing
      the study. Over the course of the study, there were four study-related adverse
      events (minor swelling and bruising related to a blood draw) and five severe
      adverse events (infant deaths) not related to study participation. Biological
      sample indicators demonstrated two blood samples collected from 95% (333 of 350
      required) infants and stool collected for 61% of reported infant diarrhea
      episodes. Anthropometry data quality indicators were extremely high (median SDs
      for weight-for-length, length-for-age and weight-for-age z-scores 1.01, 0.98, and
      1.03, respectively), likely due to extensive training, standardization, and
      monitoring efforts. CONCLUSIONS: Conducting human subjects research studies in
      low-resource settings often presents unique logistical difficulties, and
      collecting high-quality data is often a challenge. Investing in comprehensive M&E
      is important to improve participant recruitment, retention and safety, and sample
      and data quality. The M&E framework from this study can be applied to other
      longitudinal studies.

PMID- 29183281
TI  - Optimizing and evaluating the reconstruction of Metagenome-assembled microbial
      genomes.
AB  - BACKGROUND: Microbiome/host interactions describe characteristics that affect the
      host's health. Shotgun metagenomics includes sequencing a random subset of the
      microbiome to analyze its taxonomic and metabolic potential. Reconstruction of
      DNA fragments into genomes from metagenomes (called metagenome-assembled genomes)
      assigns unknown fragments to taxa/function and facilitates discovery of novel
      organisms. Genome reconstruction incorporates sequence assembly and sorting of
      assembled sequences into bins, characteristic of a genome. However, the microbial
      community composition, including taxonomic and phylogenetic diversity may
      influence genome reconstruction. We determine the optimal reconstruction method
      for four microbiome projects that had variable sequencing platforms (IonTorrent
      and Illumina), diversity (high or low), and environment (coral reefs and kelp
      forests), using a set of parameters to select for optimal assembly and binning
      tools. METHODS: We tested the effects of the assembly and binning processes on
      population genome reconstruction using 105 marine metagenomes from 4 projects.
      Reconstructed genomes were obtained from each project using 3 assemblers (IDBA,
      MetaVelvet, and SPAdes) and 2 binning tools (GroopM and MetaBat). We assessed the
      efficiency of assemblers using statistics that including contig continuity and
      contig chimerism and the effectiveness of binning tools using genome completeness
      and taxonomic identification. RESULTS: We concluded that SPAdes, assembled more
      contigs (143,718 +/- 124 contigs) of longer length (N50 = 1632 +/- 108 bp), and
      incorporated the most sequences (sequences-assembled = 19.65%). The microbial
      richness and evenness were maintained across the assembly, suggesting low contig
      chimeras. SPAdes assembly was responsive to the biological and technological
      variations within the project, compared with other assemblers. Among binning
      tools, we conclude that MetaBat produced bins with less variation in GC content
      (average standard deviation: 1.49), low species richness (4.91 +/- 0.66), and
      higher genome completeness (40.92 +/- 1.75) across all projects. MetaBat
      extracted 115 bins from the 4 projects of which 66 bins were identified as
      reconstructed metagenome-assembled genomes with sequences belonging to a specific
      genus. We identified 13 novel genomes, some of which were 100% complete, but show
      low similarity to genomes within databases. CONCLUSIONS: In conclusion, we
      present a set of biologically relevant parameters for evaluation to select for
      optimal assembly and binning tools. For the tools we tested, SPAdes assembler and
      MetaBat binning tools reconstructed quality metagenome-assembled genomes for the
      four projects. We also conclude that metagenomes from microbial communities that
      have high coverage of phylogenetically distinct, and low taxonomic diversity
      results in highest quality metagenome-assembled genomes.

PMID- 29183282
TI  - Bilateral muscle fiber and nerve influences by TNF-alpha in response to
      unilateral muscle overuse - studies on TNF receptor expressions.
AB  - BACKGROUND: TNF-alpha is suggested to be involved in muscle damage and muscle
      inflammation (myositis). In order to evaluate whether TNF-alpha is involved in
      the myositis that occurs in response to muscle overuse, the aim was to examine
      the expression patterns of TNF receptors in this condition. METHODS: A rabbit
      muscle overuse model leading to myositis in the soleus muscle was used. The
      expression patterns of the two TNF receptors Tumor Necrosis Factor Receptor type
      1 (TNFR1) and Tumor Necrosis Factor Receptor type 2 (TNFR2) were investigated. In
      situ hybridization and immunofluorescence were utilized. Immunostainings for
      desmin, NK-1R and CD31 were made in parallel. RESULTS: Immunoreactions (IR) for
      TNF receptors were clearly observed in white blood cells, fibroblasts and vessel
      walls, and most interestingly also in muscle fibers and nerve fascicles in the
      myositis muscles. There were very restricted reactions for these in the muscles
      of controls. The upregulation of TNF receptors was for all types of structures
      seen for both the experimental side and the contralateral nonexperimental side.
      TNF receptor expressing muscle fibers were present in myositis muscles. They can
      be related to attempts for reparation/regeneration, as evidenced from results of
      parallel stainings. Necrotic muscle fibers displayed TNFR1 mRNA and TNFR2
      immunoreaction (IR) in the invading white blood cells. In myositis muscles, TNFR1
      IR was observed in both axons and Schwann cells while TNFR2 IR was observed in
      Schwann cells. Such observations were very rarely made for control animals.
      CONCLUSIONS: The findings suggest that there is a pronounced involvement of TNF
      alpha in the developing myositis process. Attempts for reparation of the muscle
      tissue seem to occur via both TNFR1 and TNFR2. As the myositis process also
      occurs in the nonexperimental side and as TNF receptors are confined to nerve
      fascicles bilaterally it can be asked whether TNF-alpha is involved in the
      spreading of the myositis process to the contralateral side via the nervous
      system. Taken together, the study shows that TNF-alpha is not only associated
      with the inflammation process but that both the muscular and nervous systems are
      affected and that this occurs both on experimental and nonexperimental sides.

PMID- 29183283
TI  - Mitochondrial genome sequencing reveals potential origins of the scabies mite
      Sarcoptes scabiei infesting two iconic Australian marsupials.
AB  - BACKGROUND: Debilitating skin infestations caused by the mite, Sarcoptes scabiei,
      have a profound impact on human and animal health globally. In Australia, this
      impact is evident across different segments of Australian society, with a growing
      recognition that it can contribute to rapid declines of native Australian
      marsupials. Cross-host transmission has been suggested to play a significant role
      in the epidemiology and origin of mite infestations in different species but a
      chronic lack of genetic resources has made further inferences difficult. To
      investigate the origins and molecular epidemiology of S. scabiei in Australian
      wildlife, we sequenced the mitochondrial genomes of S. scabiei from diseased
      wombats (Vombatus ursinus) and koalas (Phascolarctos cinereus) spanning New South
      Wales, Victoria and Tasmania, and compared them with the recently sequenced
      mitochondrial genome sequences of S. scabiei from humans. RESULTS: We found
      unique S. scabiei haplotypes among individual wombat and koala hosts with high
      sequence similarity (99.1% - 100%). Phylogenetic analysis of near full-length
      mitochondrial genomes revealed three clades of S. scabiei (one human and two
      marsupial), with no apparent geographic or host species pattern, suggestive of
      multiple introductions. The availability of additional mitochondrial gene
      sequences also enabled a re-evaluation of a range of putative molecular markers
      of S. scabiei, revealing that cox1 is the most informative gene for molecular
      epidemiological investigations. Utilising this gene target, we provide additional
      evidence to support cross-host transmission between different animal hosts.
      CONCLUSIONS: Our results suggest a history of parasite invasion through
      colonisation of Australia from hosts across the globe and the potential for cross
      host transmission being a common feature of the epidemiology of this neglected
      pathogen. If this is the case, comparable patterns may exist elsewhere in the
      'New World'. This work provides a basis for expanded molecular studies into mange
      epidemiology in humans and animals in Australia and other geographic regions.

PMID- 29183284
TI  - Robust expression of tumor suppressor miRNA's let-7 and miR-195 detected in
      plasma of Saudi female breast cancer patients.
AB  - BACKGROUND: Female breast cancer is frequently diagnosed at a later stage and the
      leading cause of cancer deaths world-wide. Levels of cell-free circulating
      microRNAs (miRNAs) can potentially be used as biomarkers to measure disease
      progression in breast cancer patients in a non-invasive way and are therefore of
      high clinical value. METHODS: Using quantitative RT-PCR, circulating miRNAs were
      measured in blood samples collected from disease-free individuals (n = 34),
      triple-negative breast tumours (TNBC) (n = 36) and luminal tumours (n = 57). In
      addition to intergroup comparisons, plasma miRNA expression levels of all groups
      were analyzed against RNASeq data from cancerous breast tissue via The Cancer
      Genome Atlas (TCGA). RESULTS: A differential set of 18 miRNAs were identified in
      the plasma of breast cancer patients and 10 miRNAs were uniquely identified based
      on ROC analysis. The most striking findings revealed elevated tumor suppressor
      let-7 miRNA in luminal breast cancer patients, irrespective of subtype, and
      elevated miR-195 in plasma of TNBC breast cancer patients. In contrast, hsa-miR
      195 and let-7 miRNAs were absent from cancerous TCGA tissue and strongly
      expressed in surrounding non-tumor tissue indicating that cancerous cells may
      selectively export tumor suppressor hsa-miR-195 and let-7 miRNAs in order to
      maintain oncogenesis. CONCLUSIONS: While studies have indicated that the
      restoration of let-7 and miR-195 may be a potential therapy for cancer, these
      results suggested that tumor cells may selectively export hsa-miR-195 and let-7
      miRNAs thereby neutralizing their potential therapeutic effect. However, in order
      to facilitate earlier detection of breast cancer, blood based screening of hsa
      miR-195 and let-7 may be beneficial in a female patient cohort.

PMID- 29183285
TI  - The German version of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL
      5): psychometric properties and diagnostic utility.
AB  - BACKGROUND: The Posttraumatic Stress Disorder (PTSD) Checklist (PCL, now PCL-5)
      has recently been revised to reflect the new diagnostic criteria of the disorder.
      METHODS: A clinical sample of trauma-exposed individuals (N = 352) was assessed
      with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the PCL-5.
      Internal consistencies and test-retest reliability were computed. To investigate
      diagnostic accuracy, we calculated receiver operating curves. Confirmatory factor
      analyses (CFA) were performed to analyze the structural validity. RESULTS:
      Results showed high internal consistency (alpha = .95), high test-retest
      reliability (r = .91) and a high correlation with the total severity score of the
      CAPS-5, r = .77. In addition, the recommended cutoff of 33 on the PCL-5 showed
      high diagnostic accuracy when compared to the diagnosis established by the CAPS
      5. CFAs comparing the DSM-5 model with alternative models (the three-factor
      solution, the dysphoria, anhedonia, externalizing behavior and hybrid model) to
      account for the structural validity of the PCL-5 remained inconclusive.
      CONCLUSIONS: Overall, the findings show that the German PCL-5 is a reliable
      instrument with good diagnostic accuracy. However, more research evaluating the
      underlying factor structure is needed.

PMID- 29183286
TI  - First gene-ontology enrichment analysis based on bacterial coregenome variants:
      insights into adaptations of Salmonella serovars to mammalian- and avian-hosts.
AB  - BACKGROUND: Many of the bacterial genomic studies exploring evolution processes
      of the host adaptation focus on the accessory genome describing how the gains and
      losses of genes can explain the colonization of new habitats. Consequently, we
      developed a new approach focusing on the coregenome in order to describe the host
      adaptation of Salmonella serovars. METHODS: In the present work, we propose
      bioinformatic tools allowing (i) robust phylogenetic inference based on SNPs and
      recombination events, (ii) identification of fixed SNPs and InDels distinguishing
      homoplastic and non-homoplastic coregenome variants, and (iii) gene-ontology
      enrichment analyses to describe metabolic processes involved in adaptation of
      Salmonella enterica subsp. enterica to mammalian- (S. Dublin), multi- (S.
      Enteritidis), and avian- (S. Pullorum and S. Gallinarum) hosts. RESULTS: The
      'VARCall' workflow produced a robust phylogenetic inference confirming that the
      monophyletic clade S. Dublin diverged from the polyphyletic clade S. Enteritidis
      which includes the divergent clades S. Pullorum and S. Gallinarum (i). The
      scripts 'phyloFixedVar' and 'FixedVar' detected non-synonymous and non
      homoplastic fixed variants supporting the phylogenetic reconstruction (ii). The
      scripts 'GetGOxML' and 'EveryGO' identified representative metabolic pathways
      related to host adaptation using the first gene-ontology enrichment analysis
      based on bacterial coregenome variants (iii). CONCLUSIONS: We propose in the
      present manuscript a new coregenome approach coupling identification of fixed
      SNPs and InDels with regards to inferred phylogenetic clades, and gene-ontology
      enrichment analysis in order to describe the adaptation of Salmonella serovars
      Dublin (i.e. mammalian-hosts), Enteritidis (i.e. multi-hosts), Pullorum (i.e.
      avian-hosts) and Gallinarum (i.e. avian-hosts) at the coregenome scale. All these
      polyvalent Bioinformatic tools can be applied on other bacterial genus without
      additional developments.

PMID- 29183287
TI  - HIV and hepatitis B and C co-infection among people who inject drugs in Zanzibar.
AB  - BACKGROUND: People who inject drugs are at high risk of acquiring hepatitis B
      (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV) due to risky
      injection and sexual practices. The objective of this study is to investigate the
      epidemiology of HIV, hepatitis B, and hepatitis C, and co-infection of these
      viruses among people who inject drugs in Zanzibar, Tanzania. METHODS: We used
      respondent-driven sampling to identify 408 participants, from whom we collected
      demographic data, information on sexual behaviours and injection drug practices,
      and blood samples for biological testing. RESULTS: Prevalence of hepatitis B
      surface antigenaemia, HCV, and HIV infection were 5.9, 25.4, and 11.3%,
      respectively. Of the participants who were hepatitis B surface antigen (HBsAg)
      positive, 33.5% were infected with HCV and 18.8% were infected with HIV. Of the
      HCV-infected participants, 29.3% were infected with HIV. Of the participants who
      were infected with HIV, 9.0% were HBsAg positive, 66.6% had HCV and 8.5% had
      both. None of the potential risk factors we measured were associated with HBsAg
      positivity. In contrast, older age and longer duration of injection drug use were
      independently associated with HCV infection. HCV infection among people who
      inject drugs is lower in Zanzibar than in other countries, but could rise without
      proper interventions. CONCLUSIONS: These findings underscore the importance of
      screening people who inject drugs for HIV, HBsAg, and HCV; providing HBV
      vaccination to those who are eligible; initiating antiretroviral therapy for
      those who are co-infected with HIV/HBV and HIV/HCV; and introducing interventions
      that have high impact on reducing needle sharing.

PMID- 29183288
TI  - Arginase 1 deletion in myeloid cells affects the inflammatory response in
      allergic asthma, but not lung mechanics, in female mice.
AB  - BACKGROUND: (Over-)expression of arginase may limit local availability of
      arginine for nitric oxide synthesis. We investigated the significance of
      arginase1 (ARG1) for the development of airway hyperresponsiveness (AHR) and lung
      inflammation in female mice with ovalbumin (OVA)-induced allergic asthma.
      METHODS: Arg1 was ablated in the lung by crossing Arg1 fl/fl and Tie2Cre tg/-
      mice. OVA sensitization and challenge were conducted, and AHR to methacholine was
      determined using the Flexivent system. Changes in gene expression, chemokine and
      cytokine secretion, plasma IgE, and lung histology were quantified using RT-qPCR,
      ELISA, and immunohistochemistry, respectively. RESULTS: Arg1 ablation had no
      influence on the development of OVA-induced AHR, but attenuated OVA-induced
      increases in expression of Arg2 and Nos2, Slc7a1, Slc7a2, and Slc7a7 (arginine
      transporters), Il4, Il5 and Il13 (TH2-type cytokines), Ccl2 and Ccl11
      (chemokines), Ifng (TH1-type cytokine), Clca3 and Muc5ac (goblet cell markers),
      and OVA-specific IgE. Pulmonary IL-10 protein content increased, but IL-4, IL-5,
      IL-13, TNFalpha and IFNgamma content, and lung histopathology, were not affected.
      Arg1 elimination also decreased number and tightness of correlations between
      adaptive changes in lung function and inflammatory parameters in OVA/OVA-treated
      female mice. OVA/OVA-treated female mice mounted a higher OVA-IgE response than
      males, but the correlation between lung function and inflammation was lower. Arg1
      deficient OVA/OVA-treated females differed from males in a more pronounced
      decline of arginine-metabolizing and -transporting genes, higher plasma arginine
      levels, a smaller OVA-specific IgE response, and no improvement of peripheral
      lung function. CONCLUSION: Complete ablation of Arg1 in the lung affects mRNA
      abundance of arginine-transporting and -metabolizing genes, and pro-inflammatory
      genes, but not methacholine responsiveness or accumulation of inflammatory cells.

PMID- 29183289
TI  - Youth experiences of transition from child mental health services to adult mental
      health services: a qualitative thematic synthesis.
AB  - BACKGROUND: Adolescence and young adulthood is a vulnerable time during which
      young people experience many development milestones, as well as an increased
      incidence of mental illness. During this time, youth also transition between
      Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health
      Services (AMHS). This transition puts many youth at risk of disengagement from
      service use; however, our understanding of this transition from the perspective
      of youth is limited. This systematic review aims to provide a more comprehensive
      understanding of youth experiences of transition from CAMHS to AMHS, through a
      qualitative thematic synthesis of the extant literature in this area. METHOD:
      Published and unpublished literature was searched using keywords targeting three
      subject areas: Transition, Age and Mental Health. Studies were included if they
      qualitatively explored the perceptions and experiences of youth who received
      mental health services in both CAMHS and AMHS. There were no limitations on
      diagnosis or age of youth. Studies examining youth with chronic physical health
      conditions were excluded. RESULTS: Eighteen studies, representing 14 datasets and
      the experiences of 253 unique service-users were included. Youth experiences of
      moving from CAMHS and AMHS are influenced by concurrent life transitions and
      their individual preferences regarding autonomy and independence. Youth
      identified preparation, flexible transition timing, individualized transition
      plans, and informational continuity as positive factors during transition. Youth
      also valued joint working and relational continuity between CAMHS and AMHS.
      CONCLUSIONS: Youth experience a dramatic culture shift between CAMHS and AMHS,
      which can be mitigated by individualized and flexible approaches to transition.
      Youth have valuable perspectives to guide the intelligent design of mental health
      services and their perspectives should be used to inform tools to evaluate and
      incorporate youth perspectives into transitional service improvement. TRIAL
      REGISTRATION: Clinical Trial or Systematic Review Registry: PROSPERO
      International Prospective Register of Systematic Reviews CRD42014013799 .

PMID- 29183290
TI  - Modeling, validation and verification of three-dimensional cell-scaffold contacts
      from terabyte-sized images.
AB  - BACKGROUND: Cell-scaffold contact measurements are derived from pairs of co
      registered volumetric fluorescent confocal laser scanning microscopy (CLSM)
      images (z-stacks) of stained cells and three types of scaffolds (i.e., spun coat,
      large microfiber, and medium microfiber). Our analysis of the acquired terabyte
      sized collection is motivated by the need to understand the nature of the shape
      dimensionality (1D vs 2D vs 3D) of cell-scaffold interactions relevant to tissue
      engineers that grow cells on biomaterial scaffolds. RESULTS: We designed five
      statistical and three geometrical contact models, and then down-selected them to
      one from each category using a validation approach based on physically orthogonal
      measurements to CLSM. The two selected models were applied to 414 z-stacks with
      three scaffold types and all contact results were visually verified. A planar
      geometrical model for the spun coat scaffold type was validated from atomic force
      microscopy images by computing surface roughness of 52.35 nm +/-31.76 nm which
      was 2 to 8 times smaller than the CLSM resolution. A cylindrical model for fiber
      scaffolds was validated from multi-view 2D scanning electron microscopy (SEM)
      images. The fiber scaffold segmentation error was assessed by comparing fiber
      diameters from SEM and CLSM to be between 0.46% to 3.8% of the SEM reference
      values. For contact verification, we constructed a web-based visual verification
      system with 414 pairs of images with cells and their segmentation results, and
      with 4968 movies with animated cell, scaffold, and contact overlays. Based on
      visual verification by three experts, we report the accuracy of cell segmentation
      to be 96.4% with 94.3% precision, and the accuracy of cell-scaffold contact for a
      statistical model to be 62.6% with 76.7% precision and for a geometrical model to
      be 93.5% with 87.6% precision. CONCLUSIONS: The novelty of our approach lies in
      (1) representing cell-scaffold contact sites with statistical intensity and
      geometrical shape models, (2) designing a methodology for validating 3D
      geometrical contact models and (3) devising a mechanism for visual verification
      of hundreds of 3D measurements. The raw and processed data are publicly available
      from https://isg.nist.gov/deepzoomweb/data/ together with the web -based
      verification system.

PMID- 29183291
TI  - Optimization of the Hockey Fans in Training (Hockey FIT) weight loss and healthy
      lifestyle program for male hockey fans.
AB  - BACKGROUND: The health outcomes of men continue to be poorer than women globally.
      Challenges in addressing this problem include difficulties engaging men in weight
      loss programs as they tend to view these programs as contrary to the masculine
      narrative of independence and self-reliance. Researchers have been turning
      towards sports fans to engage men in health promotion programs as sports fans are
      typically male, and tend to have poor health habits. METHODS: Developed from the
      highly successful gender-sensitized Football Fans in Training program, Hockey
      Fans in Training (Hockey FIT) recruited 80 male hockey fans of the London Knights
      and Sarnia Sting who were overweight or obese into a weekly, 90-minute classroom
      education and group exercise program held over 12 weeks; a 40-week minimally
      supported phase followed. A process evaluation of the Hockey FIT program was
      completed alongside a pragmatic randomized controlled trial and outcome
      evaluation in order to fully explore the acceptability of the Hockey FIT program
      from the perspectives of coaches delivering and participants engaged in the
      program. Data sources included attendance records, participant focus groups,
      coach interviews, assessment of fidelity (program observations and post-session
      coach reflections), and 12-month participant interviews. RESULTS: Coaches enjoyed
      delivering the program and found it simple to deliver. Men valued being among
      others of similar body shape and similar weight loss goals, and found the
      knowledge they gained through the program helped them to make and maintain health
      behaviour changes. Suggested improvements include having more hockey-related
      information and activities, greater flexibility with timing of program delivery,
      and greater promotion of technology support tools. CONCLUSIONS: We confirmed
      Hockey FIT was an acceptable "gender-sensitized" health promotion program for
      male hockey fans who were overweight or obese. Minor changes were required for
      optimization, which will be evaluated in a future definitive trial. TRIAL
      REGISTRATION: NCT02396524 (Clinicaltrials.gov). Date of registration: Feb 26,
      2015.

PMID- 29183292
TI  - Assessment of macular function in patients with idiopathic Epiretinal membrane by
      multifocal Electroretinography: correlation with visual acuity and optical
      coherence tomography.
AB  - BACKGROUND: This study evaluates the macular function changes in patients with
      idiopathic macular epiretinal membrane (ERM) by multifocal electroretinography
      (mfERG) and their correlations with visual acuity and central macular thickness
      (CMT) by optical coherence tomography (OCT). METHODS: Twenty eyes of 20 patients
      with ERM underwent OCT and mfERG examinations. The response amplitude densities
      and implicit times of mfERG were compared to the control fellow eyes. Correlation
      analyses among visual acuity, central macular thickness and mfERG values in the
      central two concentric rings were performed. RESULTS: The mfERG P1 response
      amplitude densities in ring 1-2 and P1 implicit time in ring1 were significantly
      changed in epiretinal membrane eyes compared with controls (P < 0.05).
      Multivariate stepwise linear regression analyses showed LogMAR visual acuity was
      significantly correlated with CMT (P = 0.004), and also with the P1 amplitude
      density in ring 1 (P = 0.002). CMT showed significant correlation with P1
      implicit time in ring 2 (P = 0.013). CONCLUSIONS: The mfERG abnormalities show
      macular function changes and correlate with visual acuity and central macular
      thickness in eyes with ERM. In first-order mfERG responses, P1 wave changes may
      be a sensitive functional measurement for ERM patients.

PMID- 29183293
TI  - Prescribing patterns of rural family physicians: a study in Kermanshah Province,
      Iran.
AB  - BACKGROUND: The inappropriate use of drugs due to irrational prescriptions is a
      common problem in Iran, but there is little evidence of prescription patterns in
      rural family physicians. This study aimed to explore the prescribing pattern and
      rational drug use indicators for family physicians using Index of Rational Drug
      Prescribing (IRDP) in Kermanshah Province, Iran. METHODS: In this retrospective
      study, 352,399 prescriptions from 184 family physicians in 103 primary health
      care (PHC) centers were examined. As stated, an analysis was done for rational
      use indicators suggested by World Health Organization (WHO): e.g., the percentage
      of prescriptions containing antibiotics, injections, and those prescribed by a
      generic name and from a national essential medicine list, plus the average number
      of drugs per prescription; these factors were all taken into account. Rational
      drug use was studied with the IRDP. RESULTS: The average number of drugs per
      prescription was 3.14 (+/- 1.2) and the average cost per prescription was 116,740
      IRR (USD 3.6). Around 19% of prescriptions had more than four drugs, while the
      percentage of prescriptions involving antibiotics and injections was 52.1% and
      24.4%, respectively. There was 95.1% drugs prescribed by their generic name and
      95.9% were retrieved from the essential drugs list. The value of the IRDP was
      3.70 out of 5. CONCLUSION: The findings of this study showed that some degree of
      irrational drug prescribing exists among family physicians, especially in terms
      of injections, antibiotics, and polypharmacy. It is recommended that there be
      continuing education programs for physicians regarding rational prescribing for
      different kinds of medical indications. Clinical practice guidelines should also
      assist with the rational use of medicine.

PMID- 29183294
TI  - Serum albumin level as a potential marker for deciding chemotherapy or best
      supportive care in elderly, advanced non-small cell lung cancer patients with
      poor performance status.
AB  - BACKGROUND: There have been few data on the chemotherapy in elderly advanced non
      small cell lung cancer (NSCLC) patients with poor performance status (PS), and
      usefulness of chemotherapy for such patients remains unclear. The objective of
      this study was to identify factors that predicted the survival benefit of
      chemotherapy. METHODS: All consecutive elderly patients (>=75 years) with
      advanced NSCLC, Eastern Cooperative Oncology Group PS >=2, EGFR mutation wild
      type/unknown, and newly diagnosed from January 2009 to December 2012 at a
      tertiary hospital were retrospectively reviewed. RESULTS: We enrolled 59
      patients, and 31 patients received at least one chemotherapy regimen
      (chemotherapy group). However, 28 patients received best supportive care (BSC)
      alone (BSC group). The proportion of PS 2 and serum albumin levels was
      significantly higher in the chemotherapy group than in the BSC group. In the
      chemotherapy group, log-rank testing did not show statistically significant
      differences in overall survival (OS) between the single-agent therapy group and
      carboplatin-based doublet therapy group; however, the OS of patients receiving
      chemotherapy for only 1 cycle (early termination) was significantly shorter than
      patients receiving chemotherapy for >=2 cycles. Hypoalbuminemia was not only a
      risk factor for the early termination of chemotherapy but also an independent
      prognostic factor in the chemotherapy group. A receiver operating characteristic
      curve analysis showed that the best cut-off value was 3.40 g/dL. In patients with
      serum albumin levels >=3.40 g/dL, OS was significantly better in the chemotherapy
      group than in the BSC group (p = 0.0156), however, patients with serum albumin
      levels <3.40 g/dL exhibited poor prognosis regardless of the presence or absence
      of chemotherapy. CONCLUSION: In the elderly NSCLC patients with poor PS, serum
      albumin levels may help identify certain patient populations more likely to
      receive a survival benefit of systemic chemotherapy.

PMID- 29183295
TI  - VDJ gene usage among B-cell receptors in ABO-incompatible kidney transplantation
      determined by RNA-seq Transcriptomic analysis.
AB  - BACKGROUND: Studies on B-cell subtypes and V(D)J gene usage of B-cell receptors
      in kidney transplants are scarce. This study aimed to investigate V(D)J gene
      segment usage in ABO-incompatible (ABOi) kidney transplant (KT) patients compared
      to that in ABO-compatible (ABOc) KT patients. METHODS: We selected 16 ABOi KT
      patients with accommodation (ABOiA), 6 ABOc stable KT patients (ABOcS), and 6
      ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at
      day 10, whose graft tissue samples had been stored in the biorepository between
      2010 and 2014. Complete transcriptomes of graft tissues were sequenced and
      analyzed through RNA sequencing (RNA-seq). The international ImMunoGeneTics
      information system (IMGT(r)) was used for in-depth comparison of V(D)J gene
      segment usage. RESULTS: The mean age of the 28 KT recipients was 43.3 +/- 12.8
      years, and 53.6% were male. By family, IGHV3, IGHJ4, IGLV2, and IGLJ3 gene
      segments were most frequently used in all groups, and their usage was not
      statistically different among the three patient groups. While IGKV3 was most
      frequently used in both the ABOiA and ABOiR groups, IGKV1 was most commonly used
      in the ABOcS group. In addition, while IGKJ1 was most commonly used in the ABOiA
      and ABOcS groups, IGKJ4 was most frequently used in the ABOiR group. According to
      individual gene segments, IGHV4-34 and IGHV4-30-2 were more commonly used in the
      ABOiR group than in the ABOiA group, and IGHV6-1 was more commonly used in the
      ABOcS group than in the ABOiR group. IGLV7-43 was more commonly used in the ABOcS
      group than in the ABOi group. However, technical variability, small sample size,
      and potential confounding effects of Rituximab or HLA mismatching are limitations
      of our study. CONCLUSIONS: Our findings suggest that RNA-seq transcriptomic
      analyses can provide information on the V(D)J gene usage of B-cell receptors and
      the mechanisms of accommodation and immune reaction in ABOi KT.

PMID- 29183296
TI  - Theories, models and frameworks used in capacity building interventions relevant
      to public health: a systematic review.
AB  - BACKGROUND: There is limited research on capacity building interventions that
      include theoretical foundations. The purpose of this systematic review is to
      identify underlying theories, models and frameworks used to support capacity
      building interventions relevant to public health practice. The aim is to inform
      and improve capacity building practices and services offered by public health
      organizations. METHODS: Four search strategies were used: 1) electronic database
      searching; 2) reference lists of included papers; 3) key informant consultation;
      and 4) grey literature searching. Inclusion and exclusion criteria are outlined
      with included papers focusing on capacity building, learning plans, professional
      development plans in combination with tools, resources, processes, procedures,
      steps, model, framework, guideline, described in a public health or healthcare
      setting, or non-government, government, or community organizations as they relate
      to healthcare, and explicitly or implicitly mention a theory, model and/or
      framework that grounds the type of capacity building approach developed. Quality
      assessment were performed on all included articles. Data analysis included a
      process for synthesizing, analyzing and presenting descriptive summaries,
      categorizing theoretical foundations according to which theory, model and/or
      framework was used and whether or not the theory, model or framework was implied
      or explicitly identified. RESULTS: Nineteen articles were included in this
      review. A total of 28 theories, models and frameworks were identified. Of this
      number, two theories (Diffusion of Innovations and Transformational Learning),
      two models (Ecological and Interactive Systems Framework for Dissemination and
      Implementation) and one framework (Bloom's Taxonomy of Learning) were identified
      as the most frequently cited. CONCLUSIONS: This review identifies specific
      theories, models and frameworks to support capacity building interventions
      relevant to public health organizations. It provides public health practitioners
      with a menu of potentially usable theories, models and frameworks to support
      capacity building efforts. The findings also support the need for the use of
      theories, models or frameworks to be intentional, explicitly identified,
      referenced and for it to be clearly outlined how they were applied to the
      capacity building intervention.

PMID- 29183297
TI  - Predictors of early adulthood hypertension during adolescence: a population-based
      cohort study.
AB  - BACKGROUND: Some longitudinal studies have shown that blood pressure tracks from
      adolescence to adulthood, yet there is limited evidence regarding the predictive
      factors of adulthood hypertension during adolescence. This study was conducted
      within the framework of the Tehran Lipid and Glucose Study (TLGS) to investigate
      the role of some factors in adolescence, measured in the first examination (1999
      2001), to predict adulthood hypertension in the 4th examination (2009-2011).
      METHODS: Overall, 1579 subjects, aged 10-19 years, were used for the analysis of
      the current study. Mean age (SD) of participants at the baseline was 14.2 (2.5)
      years and 55% of them were female. A forward stepwise approach (p-value <0.2 for
      enter and >0.05 for removal) was considered to keep significant covariates among
      common variables including gender, body mass index, waist circumference, wrist
      and hip circumferences, fasting blood sugar, triglycerides, high density
      lipoprotein cholesterol, total cholesterol (TC), systolic (SBP) and diastolic
      blood pressure (DBP). Variance inflation factor (VIF) showed some
      multicollinearity for anthropometric variables (VIFs between 3.5 and 10).
      Multivariable logistic regression revealed that gender, blood pressure, wrist
      circumference and total cholesterol in adolescents are important predictors for
      adulthood hypertension. RESULTS: The risk increased by 4% and 39% per each 10
      mmHg and 1 mmol/L increase in SBP/DBP and TC, respectively; additionally, females
      had a 70% lower risk. Among anthropometric variables, wrist circumference
      remained in the model, with 50% per centimeter increase in the risk of
      hypertension. CONCLUSIONS: Wrist circumferences and TC had significant roles in
      predicting hypertension through adolescence to adulthood.

PMID- 29183298
TI  - Differences in corneal clinical findings after standard and accelerated cross
      linking in patients with progressive keratoconus.
AB  - BACKGROUND: The purpose of this study was to identify differences in clinical
      corneal findings after standard and accelerated epithelial off cross-linking
      (CXL) during a long-term follow-up. METHODS: Two hundred forty-one patients (184
      male) were included in this monocentric, retrospective, non-randomized and
      unmasked study. One hundred forty-eight eyes were treated with the accelerated
      protocol and 138 with the standard protocol with epithelial off CXL, if diagnosed
      with keratoconus and a progression in Kmax of more than one dioptre during the
      preceding 6 months, plus a minimal pachymetry measurement of 400 MUm in
      keratometry (Pentacam, Oculus GmbH, Wetzlar, Germany). Exclusion criteria were
      previous surgery, other corneal conditions or age above 50 years. Follow-up time
      was 36 months with clinical examination and keratometry at every visit. Outcome
      measures were the observed rate of corneal changes, differences between treatment
      groups and correlation with keratometry measurements. RESULTS: In patients with
      accelerated CXL, significantly more clear corneas were seen at three (p = 0.015)
      and six (p = 0.002) months after surgery than following the standard protocol.
      The rate of clear corneas dropped from 52.2% pre-operation (OP) to a minimum of
      19.3% after 6 months in the standard protocol group compared with 50.7% clear
      corneas pre-OP and a minimum of 40.8% in the accelerated group. In the standard
      protocol group, more striae were found 3 months after intervention than in the
      accelerated group (p = 0.05). CONCLUSIONS: In patients with accelerated CXL,
      fewer morphological corneal changes were observed than after conventional CXL.
      However, rarely, corneal changes persisted for a long time.

PMID- 29183299
TI  - Tobacco-smoking induced GPR15-expressing T cells in blood do not indicate
      pulmonary damage.
AB  - BACKGROUND: Recently, it was shown that chronic tobacco smoking evokes specific
      cellular and molecular changes in white blood cells by an excess of G protein
      coupled receptor 15 (GPR15)-expressing T cells as well as a hypomethylation at
      DNA CpG site cg05575921 in granulocytes. In the present study, we aimed to
      clarify the general usefulness of these two biomarkers as putative signs of non
      cancerous change in homeostasis of the lungs. METHODS: In a clinical cohort
      consisting of 42 patients with chronic obstructive pulmonary disease (COPD),
      interstitial lung disease (ILD) and pneumonia and a control cohort of 123
      volunteers, the content of GPR15-expressing blood cells as well as the degree of
      methylation at cg05575921 were analysed by flow-cytometry and pyrosequencing,
      respectively. Smoking behaviour was estimated by questionnaire and cotinine level
      in plasma. RESULTS: Never-smoking patients could be distinguished from former and
      current smokers by both the proportion of GPR15-expressing T cells as well as
      cg05575921 methylation in granulocytes, with 100% and 97% specificity and 100%
      sensitivity, respectively. However, both parameters were not affected by lung
      diseases. The degrees of both parameters were not changed neither in non-smoking
      nor smoking patients, compared to appropriate control cohorts of volunteers.
      CONCLUSIONS: The degree of GPR15-expressing cells among T cells as well as the
      methylation at cg05575921 in granulocytes in blood are both rather signs of
      tobacco-smoking induced systemic inflammation because they don't indicate
      specifically non-cancerous pathological changes in the lungs.

PMID- 29183300
TI  - Metabolic syndrome and its components among university students in Kenya.
AB  - BACKGROUND: Metabolic syndrome refers to a cluster of interrelated disorders
      which occur together causing an increase in the risk of developing cardiovascular
      disease and diabetes. The university population is an understudied group despite
      the increase in the frequency of related disorders and metabolic risk factors
      e.g. obesity and diabetes, majorly due to the assumption that they are in their
      most active phase of life therefore healthy. This study looked at metabolic
      syndrome, the sedentary lifestyles and dietary habits present among university
      students attending Mount Kenya University, main campus. METHODS: Stratified
      sampling was used to select participants. Self-administered questionnaires were
      issued to participants after a signed consent had been obtained following which
      clinical assessments and biochemical measures were performed. They included blood
      pressure, fasting blood glucose, triglycerides, high density lipoprotein
      cholesterol, anthropometric measurements; height, weight, BMI and waist
      circumference. Pearson's chi-square tests and non-parametric independent t-test
      were used to analyze the prevalence of metabolic syndrome criteria per gender,
      the number of metabolic syndrome criteria per BMI and prevalence of metabolic
      syndrome criteria per BMI category. RESULTS: The study established that 1.9% of
      the participants met the criteria for diagnosis of metabolic syndrome according
      to HJSS criteria. Among the elements, there was statistical difference in gender
      BMI and waist circumference. 11.8% of subjects had two metabolic syndrome
      components while 3.1% had three components while none of the subjects had all six
      components. Elevated triglycerides was the most prevalent defining component for
      metabolic syndrome. There is a statistically significant relationship between
      sedentary lifestyle and dietary habits as risk factors to metabolic syndrome.
      CONCLUSION: Young adults in university have begun developing metabolic syndrome
      and the risk of developing the syndrome continues to increase with the components
      being reported in early age. Educational initiatives to encourage healthy eating
      should be conducted within school premises in order to reinforce the message on
      healthy diets and physical exercise. Pre-admission screening to identify at risk
      students should be conducted. Targeted interventions development through a
      mandatory extra co-curricular program should be enforced to positively engage
      those at risk.

PMID- 29183301
TI  - Consistent condom use and its correlates among female sex workers at hair salons:
      a cross-sectional study in Zhejiang province, China.
AB  - BACKGROUND: This study investigated condom use among female sex workers (FSWs) at
      hair salons during commercial sexual interactions over 1 month. We explored the
      associations of such use with various sexual behaviours, HIV/STI risk perception
      and related knowledge, self-efficacy regarding condom use, exposure to
      behavioural interventions, and other factors. This type of information has not
      been reported in China and is critical for designing and modifying programs aimed
      at preventing HIV/STI transmission in this group of FSWs and their clients.
      METHODS: Our data were derived from a large cross-sectional study conducted among
      low-tier FSWs in 21 counties within Zhejiang province, China. Data were collected
      from September to November 2013.Bivariable and multiple logistic regression
      analyses were used to identify factors associated with self-reported consistent
      condom use among FSWs working at hair salons. RESULTS: Of 1682 FSWs working at
      hair salons, 50.5% consistently used condom with clients during the previous
      month. Multivariable analysis revealed that condom use for commercial sex,
      consistent vaginal douching after commercial sex, adopting contraceptive
      measures, high scores on perceived self-efficacy regarding condom use, and
      exposure to interventions were associated with self-reported consistent condom
      use; early initiation of commercial sex, experiences with oral sex,
      rarely/sometimes/often using oral contraceptives, and having seen a doctor were
      associated with not using condoms. CONCLUSIONS: Commercial sex is not effectively
      protected, and behavioural interventions targeting FSWs should take into account
      the various factors that are correlated to condom use.

PMID- 29183302
TI  - Individual, social and environmental determinants of smokeless tobacco and betel
      quid use amongst adolescents of Karachi: a school-based cross-sectional survey.
AB  - BACKGROUND: With 600 million people using betel quid (BQ) globally, and smokeless
      tobacco (SLT) use being more wide-spread; the duo is an uphill public health
      concern in South Asian countries. SLT and/or BQ use increases the risk for
      morbidity and mortality from oral cancer. Because SLT and/or BQ use is initiated
      during adolescence, it renders this group more vulnerable; and particular
      attention is needed to curb SLT and/or BQ use to reduce related disease burden.
      We aimed to observe the differential individual, social and environmental
      features amongst SLT and/or BQ users to determine the key influencers of its use
      in adolescents. METHODS: This study was a cross-sectional survey of 2140
      adolescents from secondary schools of Karachi, Pakistan. The main outcome measure
      was SLT and/or BQ use based on their consumption in the past 30 days. Univariate
      and multivariate regression binary logistic analyses were employed while
      reporting results in both crude form and adjusted odds ratio (after adjusting for
      all remaining individual, social and environmental level variables) with 95%
      confidence level. A p-value of < .05 was considered significant for all analyses.
      RESULTS: The overall prevalence of SLT and/or BQ use was 42.6% (n = 912) of the
      total sample. The SLT and/or BQ consumer group had more males than females. A
      significant proportion of user (n = 558, 61.2%) was found in co-education
      schools. Students whose peers (OR = 6.79, 95% CI 4.67-9.87, p-value <0.001)
      and/or either of the parents (OR = 2.16, 95% CI 1.73-2.65, p-value <0.001) used
      SLT and/or BQ, alongside, adolescents who had not attended knowledge based
      sessions in schools regarding harmful effects of SLT and/or BQ were more likely
      to consume it. It's availability with outside school hawkers increased the odds
      of its use by 6 times, as indicated by both univariate and multivariate models
      after adjusting for the remaining variables. CONCLUSION: In conclusion, students
      studying in co-education, parents and peers use, lack of knowledge based sessions
      on harmful health effects of SLT and/or BQ, and easy availability of the product
      from hawkers outside school all contribute towards enhanced risk of SLT and/or BQ
      use in adolescents.

PMID- 29183303
TI  - Link between neurodegeneration and trabecular meshwork injury in glaucomatous
      patients.
AB  - BACKGROUND: Glaucoma is classified as a neurodegenerative disease. However, the
      biomarkers of neurodegeneration in the aqueous humour of primary open angle
      glaucoma (POAG) eyes have not been quantitatively examined yet. In this study,
      levels of neurodegeneration-related cytokines in the aqueous humour of POAG eyes
      were measured and compared with those of non-glaucoma (senile cataract) control
      eyes. METHODS: This cross-sectional study included 24 patients (24 eyes) with
      POAG and 22 patients (22 eyes) with cataract. Aqueous humour samples were
      collected before the commencement of phacoemulsification surgery. The
      concentrations of brain-derived neurotrophic factor (BDNF), cathepsin D,
      myeloperoxidase (MPO), soluble intercellular adhesion molecule-1 (sICAM-1),
      soluble neural cell adhesion molecule (sNCAM), soluble vascular cell adhesion
      molecule-1 (sVCAM-1), and plasminogen activator inhibitor-1 (PAI-1) were measured
      using the Luminex suspension array technique. The clinical characteristics of the
      patients were also obtained for correlation analysis. RESULTS: Compared with the
      cataract group, the levels of cathepsin D (P < 0.001), sNCAM (P < 0.001) and
      sVCAM-1 (P = 0.007) were significantly higher in the aqueous humour samples from
      POAG. The levels of BDNF, sICAM-1, MPO and PAI-1 did not differ among the groups.
      Mean deviation (MD) values measured by the Humphrey Visual Field Analyzer were
      significantly associated with levels of cathepsin D (P < 0.001; rho= - 0.668),
      sICAM-1 (P = 0.003; rho= - 0.579), sVCAM-1(P < 0.001; rho= - 0.695), and PAI-1 (P
      = 0.007; rho= - 0.533). The cytokines showed a positive correlation among each
      other (P < 0.0083). CONCLUSION: These data suggest that POAG patients had
      elevated levels of multiple biomarkers of neurodegeneration in the aqueous
      humour, and these elevated biomarkers may be related to trabecular meshwork
      injury. TRIAL REGISTRATION: This study was registered in the Chinese Clinical
      Trial Registry ( ChiCTR-OOC-16008516 ) on May 22, 2016.

PMID- 29183304
TI  - Dental caries experience and determinants in young adults of the Northern State
      Medical University, Arkhangelsk, North-West Russia: a cross-sectional study.
AB  - BACKGROUND: Little information exists about the experience of and risk factors
      for dental caries in young adults in Russia. We investigated dental caries
      experience and determinants in medical and dental students in North-West Russia.
      METHODS: This cross-sectional study included 442 medical and 309 dental
      undergraduate students of Russian nationality aged 18-25 years from the Northern
      State Medical University, Arkhangelsk, Russia. Information on socio-demographic
      factors and oral health behaviour (regularity of dental visits, frequency of
      tooth-brushing, using toothpaste with fluoride, and skipping tooth-brushing) was
      obtained from a structured, self-administered questionnaire. Dental caries
      experience was based on the decayed (D) missing (M) filled (F) teeth (T) index
      and the Significant Caries (SiC) index, which were assessed through dental
      examination. Students with a DMFT index >=9 were placed in the SiC group.
      Negative binomial hurdle and multivariable binary logistic regressions were used
      for statistical analyses. RESULTS: The prevalence of dental caries (DMFT >0) was
      96.0%, overall mean DMFT index was 7.58 (DT: 0.61, MT: 0.12, and FT: 6.84), and
      the corresponding SiC index was 12.50. Age 21-25 years (incidence rate ratio
      [IRR] = 1.09, 95% confidence interval [CI]: 1.01-1.18), being a female (IRR =
      1.10, 95% CI: 1.01-1.20), high subjective socioeconomic status (SES) [IRR = 1.11,
      95% CI: 1.02-1.21], and skipping tooth-brushing (IRR = 1.09, 95% CI: 1.00-1.19)
      were associated with a higher DMFT index. DMFT index also increased among
      students who reported regular dental visits (IRR = 1.22, 95% CI: 1.10-1.36), but
      their odds of being in the dental caries-free group decreased (odds ratio [OR] =
      0.38, 95% CI: 0.18-0.82). Significant predictors of being categorised to the SiC
      group were older age (OR = 1.41, 95% CI: 1.03-1.92), high subjective SES (OR =
      1.57, 95% CI: 1.13-2.19), and regular dental visits (OR = 2.34, 95% CI: 1.56
      3.51). CONCLUSIONS: A high prevalence of dental caries and high DMFT index, with
      a dominance of FT, were observed in our Russian medical and dental students. Age,
      sex, subjective SES, regular dental visits, and skipping tooth-brushing were
      determinants of dental caries experience.

PMID- 29183305
TI  - Hemodynamic benefits of celiac artery release for ruptured right gastric artery
      aneurysm associated with median arcuate ligament syndrome: a case report.
AB  - BACKGROUND: It has been reported that median arcuate ligament syndrome is closely
      associated with gastric or pancreaticoduodenal artery aneurysms. Hemodynamic
      state plays an important role in the formation of the aneurysms. These aneurysms
      are treated with open resection or endovascular exclusion. However, whether
      revascularization of the celiac artery can prevent the aneurysm formation is
      unknown. This report indicated a possibility that prophylactic revascularization
      for celiac artery stenosis resulted in decreased shear stress on the collaterals,
      which may otherwise be susceptible to new aneurysms. CASE PRESENTATION: This
      report describes a 51-year-old man who presented with epigastric pain at our
      hospital. According to contrast enhanced computed tomography (CT), he was
      diagnosed with a ruptured right gastric artery aneurysm and celiac artery
      stenosis caused by the median arcuate ligament (MAL). He had a vascular anomaly
      of the common hepatic artery arising from the superior mesenteric artery (SMA).
      His vital signs were stable. We informed him of the situation and he chose open
      surgery rather than endovascular treatment. Following, we resected the aneurysm
      and transected the MAL. Intraoperative angiography after transection of the MAL
      showed the antegrade blood flow to the splenic artery instead of the retrograde
      flow via the prominent collaterals. Follow-up CT confirmed narrowed collateral
      vessels between the SMA and the celiac artery without de-novo aneurysms.
      CONCLUSION: While the necessity of celiac artery release could be questioned, the
      present case supports the hemodynamic benefits of MAL transection in terms of de
      novo aneurysm prevention.

PMID- 29183306
TI  - ACDF vs TDR for patients with cervical spondylosis - an 8 year follow up study.
AB  - BACKGROUND: ACDF has been considered as the gold standard in the treatment of
      single level cervical disk protrusion. However, it may cause adjacent level
      degeneration due to regional biomechanical changes. TDR has been applied with
      satisfactory results for over a decade, but there is no consensus if TDR is safer
      and more efficient than ACDF. The current study was carried out to compare the
      efficiency and safety of TDR and ACDF in the treatment of patients with single
      level cervical disk protrusion. METHODS: One hundred forty-five consecutive
      patients who underwent either TDR or ACDF in our center were included in the
      current study. Time of surgery, intraoperative blood loss, VAS arm and neck pain
      scores, ROM, ODI, SF36 and Patient satisfaction were compared before the surgery,
      after the surgery, and during follow up 1, 3, 5, 8 years after the surgery.
      RESULTS: The time of surgery was 64.6 +/- 20.7 min in the ACDF group and 69.4 +/-
      19.3 min in the TDR group; intraoperative hemorrhage was 67.2 +/- 14.3 ml in ACDF
      group and 70.7 +/- 18.6 ml in TDR group. There were no significant differences
      between two groups concerning time of surgery and intraoperative blood loss. No
      differences were found concerning patient satisfaction between the two groups
      during the follow up (P > 0.05). Significant differences were found between the
      groups concerning VAS arm and neck pain scores, ROM, ODI and SF36 after the
      surgery and during the 8 year follow up. CONCLUSION: TDR may be a more effective
      approach than ACDF for treating patients with single level cervical disk
      protrusion.

PMID- 29183307
TI  - The immediate effect of muscle release intervention on muscle activity and
      shoulder kinematics in patients with frozen shoulder: a cross-sectional,
      exploratory study.
AB  - BACKGROUND: Contractile tissue plays an important role in mobility deficits in
      frozen shoulder (FS). However, no study has assessed the effect of the muscle
      release technique on the muscle activation and kinematics in individuals with FS.
      The purposes of this study were to assess the differences in shoulder muscle
      activity and kinematics between the FS and asymptomatic groups; and to determine
      the immediate effects of muscle release intervention in the FS group. METHODS:
      Twenty patients with FS and 20 asymptomatic controls were recruited. The outcome
      measures included muscle activity of the upper and lower trapezius (UT and LT),
      infraspinatus (ISp), pectoralis major (PM), and teres major (TM), shoulder
      kinematics (humeral elevation, scapular posterior tilt (PT) and upward rotation
      (UR), shoulder mobility, and pain. Participants in the FS group received one
      session of heat and manual muscle release. Measurements were obtained at
      baseline, and immediately after intervention. Multivariate analysis of variance
      was used for data analysis. The level of significance was set at alpha=0.05.
      RESULTS: Compared to the controls, the FS group revealed significantly decreased
      LT (difference =55.89%, P=0.001) and ISp muscle activity (difference =26.32%, P
      =0.043) during the scaption task, and increased PM activity (difference =6.31%, P
      =0.014) during the thumb to waist task. The FS group showed decreased humeral
      elevation, scapular PT, and UR (difference = 35.36 degrees , 10.18 degrees , 6.73
      degrees  respectively, P <0.05). Muscle release intervention immediately
      decreased pain (VAS drop 1.7, P <0.001); improved muscle activity during scaption
      (UT: 12.68% increase, LT: 35.46% increase, P <0.05) and hand to neck (UT: 12.14%
      increase, LT: 34.04% increase, P <0.05) task; and increased peak humeral
      elevation and scapular PT during scaption (95.18 degrees +/-15.83 degrees  to
      98.24 degrees +/-15.57 degrees , P=0.034; 11.06 degrees +/-3.94 degrees  to 14.36
      degrees +/-4.65 degrees , P=0.002), and increased scapular PT during the hand to
      neck (9.47 degrees +/-3.86 degrees  to 12.80 degrees +/-8.33 degrees , P=0.025)
      task. No statistical significance was found for other group comparisons or
      intervention effect. CONCLUSION: Patients with FS presented with altered shoulder
      muscle activity and kinematics, and one-session of heat and manual muscle release
      showed beneficial effects on shoulder muscle performance, kinematics, mobility,
      and pain. TRIAL REGISTRATION: Retrospectively registered on Jan 18, 2016 (ACTRN
      12616000031460 ).

PMID- 29183308
TI  - Frequency of visits and examinations in the Public Dental Service in Finland - a
      retrospective analysis, 2001-2013.
AB  - BACKGROUND: This study aimed to investigate longitudinally examination and
      visiting patterns in the Finnish Public Dental Service (PDS) and to relate these
      to patients' treatment needs and international recommendations on examination
      intervals. METHODS: Data on patients and their dental visits in the period 2001
      2013 were collected from five municipal PDS-units serving a total population of
      320,000 inhabitants and using the same database system. Ethical approval was
      given by the National Institute for Health and Welfare (THL) and permissions to
      use local data by the directors of health services in each unit. For each year,
      the numbers of visitors, those examined and those in need of basic periodontal or
      caries treatment (CPI >2 and D + d > 0) were calculated separately for young
      people (< 18 years), the working-aged (18-64 years) and the elderly (65+ years).
      Each individual's examination and visiting intervals were counted. Multilevel
      modelling was used to study probabilities of being examined or in need of
      treatment and differences in examination and visiting intervals between groups
      and over time. RESULTS: From 2001 to 2013, the number of visitors increased by
      39.3% and the working-aged became the biggest patient group rather than the
      young. Compared with adults, the young were five times more likely to be examined
      (OR = 4.97) and three times less likely to require treatment (OR = 0.31). On
      average, 37% of the young, 73% of the working-aged and 63% of the elderly needed
      basic treatment. Multi-level analysis showed that the young had the shortest
      examination intervals and the working aged the longest (0.50 years longer). Most
      examination intervals of the young and the elderly were 1 year (65.2 - 77.0%),
      but only half (49.5%) of the working-aged were re-examined within 1 year. Over
      time, the examination intervals increased slightly in all groups. Most visiting
      intervals remained at 1 year. CONCLUSION: Young patients had mostly annual or
      biannual examinations, in line with recommendations. The examination intervals of
      working aged adults were considerably longer, and more of them needed treatment.
      The share of elderly among visitors remained low. The PDS seems to have access
      barriers for adults.

PMID- 29183309
TI  - Assessment of the effects of skin microneedling as adjuvant therapy for facial
      melasma: a pilot study.
AB  - BACKGROUND: Melasma is a common chronic and relapsing acquired dyschromia. Skin
      microneedling was reported resulting sustained long-term improvement of
      recalcitrant melasma, however, the exact mechanism that promotes this skin
      lightening is not known. This study aimed to investigate clinical and histologic
      alterations promoted by skin microneedling in facial melasma. METHODS: Open pilot
      trial including six women with facial refractory melasma submitted to two
      sessions of microneedling (1.5 mm) each 30 days followed by daily triple
      combination and broad-spectrum sunscreen. Comparison of pretreatment (T0) and 15
      days after last microneedling procedure (T45) was made by standardized pictures,
      skin colorimetry, MASI, MELASQoL and histological parameters (haematoxylin-eosin,
      picrosirius-red, periodic acid Schiff and Fontana-Masson staining). RESULTS: The
      age of the subjects varied from 34 to 46 years-old, the phototypes were III and
      IV (Fitzpatrick), and age of melasma onset was 20 to 38 years. Improvement of
      melasma was perceived in all subjects. There was a significant reduction of MASI
      score (-70%), MELASQoL (-55%) and increase in L* (+13%) colorimetric value (p <
      0.03). All cases evidenced epithelium thickening, decrease in melanin
      pigmentation and densification of upper dermis collagen (p = 0.03). Patients were
      followed by 6 months under broad-spectrum sunscreen and triple combination
      without relapse. CONCLUSION: In addition to classic treatment (broad-spectrum
      sunscreen and triple combination), skin microneedling promoted clinical and
      histological improvement of refractory facial melasma.

PMID- 29183310
TI  - Reasons for encounters and psychiatric comorbidity in an urban Bavarian primary
      care out-of-hour service - results of a cross sectional study.
AB  - BACKGROUND: International studies have shown a contribution of psychiatric
      comorbidity to high utilization rates in out-of-hour primary care (OOHC). Up to
      now, the impact of psychiatric comorbidity in German OOHC remains unclear.
      Therefore, we aimed to investigate reasons for encounter (RFE), possible
      psychiatric comorbidity, utilization rates, and a possible association between
      utilization rate and psychiatric comorbidity among patients of an urban OOHC
      unit. METHODS: In a cross-sectional, prospective, naturalistic study five hundred
      self-referred patients completed a self-designed questionnaire addressing RFE,
      past office visits and personal information. Additionally, we employed three
      validated questionnaires (PHQ-9, PHQ-15 and GAD-7) to screen for mental
      disorders. We collected information about past visits through computerized
      patients' charts. Diagnoses were classified according to the International
      Classification of Primary Care-2. RESULTS: The most frequent RFE were
      musculoskeletal complaints (36%), followed by respiratory diseases (13%),
      gastrointestinal problems (10%), skin conditions (8%) and urologic ailments (6%).
      Of the included patients 58% were working fulltime and 61% had greater than or
      equal to 10 years of education. The mean age was 37.3 in females and 40.5 years
      in males. Prevalence of psychiatric comorbidity was 27%. Only 3% visited the
      office more than twice over a 12 months period. We could not find an association
      between high utilization and psychiatric comorbidity. CONCLUSION: In this study,
      musculoskeletal complaints were the most frequent RFE. Patients were
      predominantly young, employed and educated. The prevalence of psychiatric
      comorbidity was similar to the prevalence in common general practitioner offices
      and showed no significant relation to frequent attendance. This information might
      help to prepare physicians better for patient care in OOHC.

PMID- 29183311
TI  - Successful access to the ampulla for endoscopic retrograde
      cholangiopancreatography in patients with situs inversus totalis: a case report.
AB  - BACKGROUND: Although various endoscopic techniques in situs inversus have been
      reported, endoscopic retrograde cholangiopancreatography (ERCP) in patients with
      situs inversus is always challenging even for an experienced endoscopist. We
      performed ERCP using two different techniques, and compare the merits of each
      technique. CASE PRESENTATION: A 74-year-old woman presented with epigastric pain
      and jaundice for 3 days. Computed tomography revealed diffuse dilatation of the
      biliary tree, with multiple intrahepatic duct and common bile duct (CBD) stones,
      in addition to situs inversus totalis. ERCP was performed twice for CBD stone to
      remove the CBD stones using two techniques. For the first technique used, the
      patient was placed in a prone position with the endoscopist on the right side of
      the table. First, the endoscope was rotated 180 degrees  counterclockwise in the
      stomach, and was then shortened by turning 180 degrees  the counterclockwise
      again in the duodenum. For the second technique, we assessed the second portion
      of the duodenum by following the lesser curvature, while slowly turning the
      endoscope clockwise. CONCLUSION: We present an unusual case of biliary stones in
      a patient with situs inversus who was treated using modified ERCP techniques.

PMID- 29183312
TI  - Integrated community case management in a peri-urban setting: a qualitative
      evaluation in Wakiso District, Uganda.
AB  - BACKGROUND: Integrated community case management (iCCM) strategies aim to reach
      poor communities by providing timely access to treatment for malaria, pneumonia
      and diarrhoea for children under 5 years of age. Community health workers, known
      as Village Health Teams (VHTs) in Uganda, have been shown to be effective in hard
      to-reach, underserved areas, but there is little evidence to support iCCM as an
      appropriate strategy in non-rural contexts. This study aimed to inform future
      iCCM implementation by exploring caregiver and VHT member perceptions of the
      value and effectiveness of iCCM in peri-urban settings in Uganda. METHODS: A
      qualitative evaluation was conducted in seven villages in Wakiso district, a
      rapidly urbanising area in central Uganda. Villages were purposively selected,
      spanning a range of peri-urban settlements experiencing rapid population change.
      In each village, rapid appraisal activities were undertaken separately with
      purposively selected caregivers (n = 85) and all iCCM-trained VHT members (n =
      14), providing platforms for group discussions. Fifteen key informant interviews
      were also conducted with community leaders and VHT members. Thematic analysis was
      based on the 'Health Access Livelihoods Framework'. RESULTS: iCCM was perceived
      to facilitate timely treatment access and improve child health in peri-urban
      settings, often supplanting private clinics and traditional healers as first
      point of care. Relative to other health service providers, caregivers valued
      VHTs' free, proximal services, caring attitudes, perceived treatment quality,
      perceived competency and protocol use, and follow-up and referral services. VHT
      effectiveness was perceived to be restricted by inadequate diagnostics, limited
      newborn care, drug stockouts and VHT member absence - factors which drove
      utilisation of alternative providers. Low community engagement in VHT selection,
      lack of referral transport and poor availability of referral services also
      diminished perceived effectiveness. The iCCM strategy was widely perceived to
      result in economic savings and other livelihood benefits. CONCLUSIONS: In peri
      urban areas, iCCM was perceived as an effective, well-utilised strategy,
      reflecting both VHT attributes and gaps in existing health services. Depending on
      health system resources and organisation, iCCM may be a useful transitional
      service delivery approach. Implementation in peri-urban areas should consider
      tailored community engagement strategies, adapted selection criteria, and
      assessment of population density to ensure sufficient coverage.

PMID- 29183313
TI  - Location of unaccessible implant surface areas during debridement in simulated
      peri-implantitis therapy.
AB  - BACKGROUND: An in vitro model for peri-implantitis treatment was used to identify
      areas that are clinically difficult to clean by analyzing the pattern of residual
      stain after debridement with commonly employed instruments. METHODS: Original
      data from two previous publications, which simulated surgical (SA) and non
      surgical (NSA) implant debridement on two different implant systems respectively,
      were reanalyzed regarding the localization pattern of residual stains after
      instrumentation. Two blinded examiners evaluated standardized photographs of 360
      initially ink-stained dental implants, which were cleaned at variable defect
      angulations (30, 60, or 90 degrees ), using different instrument types (Gracey
      curette, ultrasonic scaler or air powder abrasive device) and treatment
      approaches (SA or NSA). Predefined implant surface areas were graded for residual
      stain using scores ranging from one (stain-covered) to six (clean). Score
      differences between respective implant areas were tested for significance by
      pairwise comparisons using Wilcoxon-rank-sum-tests with a significance level
      alpha = 5%. RESULTS: Best scores were found at the machined surface areas (SA:
      5.58 +/- 0.43, NSA: 4.76 +/- 1.09), followed by the tips of the threads (SA: 4.29
      +/- 0.44, NSA: 4.43 +/- 0.61), and areas between threads (SA: 3.79 +/- 0.89, NSA:
      2.42 +/- 1.11). Apically facing threads were most difficult to clean (SA: 1.70 +/
      0.92, NSA: 2.42 +/- 1.11). Here, air powder abrasives provided the best results.
      CONCLUSION: Machined surfaces at the implant shoulder were well accessible and
      showed least amounts of residual stain. Apically facing thread surfaces
      constituted the area with most residual stain regardless of treatment approach.

PMID- 29183314
TI  - Does clinical supervision of healthcare professionals improve effectiveness of
      care and patient experience? A systematic review.
AB  - BACKGROUND: To ensure quality of care delivery clinical supervision has been
      implemented in health services. While clinical supervision of health
      professionals has been shown to improve patient safety, its effect on other
      dimensions of quality of care is unknown. The purpose of this systematic review
      is to determine whether clinical supervision of health professionals improves
      effectiveness of care and patient experience. METHODS: Databases MEDLINE,
      PsychINFO, CINAHL, EMBASE and AMED were searched from earliest date available.
      Additional studies were identified by searching of reference lists and citation
      tracking. Two reviewers independently applied inclusion and exclusion criteria.
      The quality of each study was rated using the Medical Education Research Study
      Quality Instrument. Data were extracted on effectiveness of care (process of care
      and patient health outcomes) and patient experience. RESULTS: Seventeen studies
      across multiple health professions (medical (n = 4), nursing (n = 7), allied
      health (n = 2) and combination of nursing, medical and/or allied health (n = 4))
      met the inclusion criteria. The clinical heterogeneity of the included studies
      precluded meta-analysis. Twelve of 14 studies investigating 38,483 episodes of
      care found that clinical supervision improved the process of care. This effect
      was most predominant in cardiopulmonary resuscitation and African health
      settings. Three of six studies investigating 1756 patients found that clinical
      supervision improved patient health outcomes, namely neurological recovery post
      cardiopulmonary resuscitation (n = 1) and psychological symptom severity (n = 2).
      None of three studies investigating 1856 patients found that clinical supervision
      had an effect on patient experience. CONCLUSIONS: Clinical supervision of health
      professionals is associated with effectiveness of care. The review found
      significant improvement in the process of care that may improve compliance with
      processes that are associated with enhanced patient health outcomes. While few
      studies found a direct effect on patient health outcomes, when provided to mental
      health professionals clinical supervision may be associated with a reduction in
      psychological symptoms of patients diagnosed with a mental illness. There was no
      association found between clinical supervision and the patient experience. REVIEW
      REGISTRATION: CRD42015029643 .

PMID- 29183315
TI  - Prevalence of poor mental health among medical students in Nepal: a cross
      sectional study.
AB  - BACKGROUND: Poor mental health among medical students is widely acknowledged.
      Studies on mental health among medical students of Nepal are lacking. Therefore,
      we conducted a study to determine the prevalence of mental disorders. METHODS: A
      cross-sectional study was conducted among medical students at KIST Medical
      College and Teaching Hospital, Nepal from December 2016 to February 2017. Our
      survey instrument consisted of the Patient Health Questionnaire (PHQ) and
      questions about socio-demographic factors, smoking, marijuana use, suicidal
      ideation and thoughts of dropping out of medical school. RESULTS: The prevalence
      rates were 29.2% (95% CI, 24.4% - 34.3%) depression, 22.4% (95% CI, 18.0% -
      26.9%) medium to highly severe somatic symptoms, 4.1% (95% CI, 2.0% - 6.2%) panic
      syndrome, 5.8% (95% CI, 3.4% - 8.3%) other anxiety syndrome, 5% (95% CI, 2.7% -
      7.3%) binge eating disorder and 1.2% (95% CI, 0.0% - 2.3%) bulimia nervosa.
      Sixteen students [4.7% (95% CI, 2.4% - 6.9%)] seriously considered committing
      suicide while in medical school. Thirty-four students [9.9% (95% CI, 6.8% -
      13.1%)] considered dropping out of medical school within the past month. About
      15% (95% CI, 11.1% - 18.6%) of the students reported use of marijuana during
      medical school. CONCLUSIONS: We found high prevalence of poor mental health among
      medical students of Nepal. Future studies are required to identify the factors
      associated with poor mental health.

PMID- 29183316
TI  - RNA sequencing reveals candidate genes and polymorphisms related to sperm DNA
      integrity in testis tissue from boars.
AB  - BACKGROUND: Sperm DNA is protected against fragmentation by a high degree of
      chromatin packaging. It has been demonstrated that proper chromatin packaging is
      important for boar fertility outcome. However, little is known about the
      molecular mechanisms underlying differences in sperm DNA fragmentation. Knowledge
      of sequence variation influencing this sperm parameter could be beneficial in
      selecting the best artificial insemination (AI) boars for commercial production.
      The aim of this study was to identify genes differentially expressed in testis
      tissue of Norwegian Landrace and Duroc boars, with high and low sperm DNA
      fragmentation index (DFI), using transcriptome sequencing. RESULTS: Altogether,
      308 and 374 genes were found to display significant differences in expression
      level between high and low DFI in Landrace and Duroc boars, respectively. Of
      these genes, 71 were differentially expressed in both breeds. Gene ontology
      analysis revealed that significant terms in common for the two breeds included
      extracellular matrix, extracellular region and calcium ion binding. Moreover,
      different metabolic processes were enriched in Landrace and Duroc, whereas immune
      response terms were common in Landrace only. Variant detection identified
      putative polymorphisms in some of the differentially expressed genes. Validation
      showed that predicted high impact variants in RAMP2, GIMAP6 and three
      uncharacterized genes are particularly interesting for sperm DNA fragmentation in
      boars. CONCLUSIONS: We identified differentially expressed genes between groups
      of boars with high and low sperm DFI, and functional annotation of these genes
      point towards important biochemical pathways. Moreover, variant detection
      identified putative polymorphisms in the differentially expressed genes. Our
      results provide valuable insights into the molecular network underlying DFI in
      pigs.

PMID- 29183317
TI  - Smad4 SUMOylation is essential for memory formation through upregulation of the
      skeletal myopathy gene TPM2.
AB  - BACKGROUND: Smad4 is a critical effector of TGF-beta signaling that regulates a
      variety of cellular functions. However, its role in the brain has rarely been
      studied. Here, we examined the molecular mechanisms underlying the post
      translational regulation of Smad4 function by SUMOylation, and its role in
      spatial memory formation. RESULTS: In the hippocampus, Smad4 is SUMOylated by the
      E3 ligase PIAS1 at Lys-113 and Lys-159. Both spatial training and NMDA injection
      enhanced Smad4 SUMOylation. Inhibition of Smad4 SUMOylation impaired spatial
      learning and memory in rats by downregulating TPM2, a gene associated with
      skeletal myopathies. Similarly, knockdown of TPM2 expression impaired spatial
      learning and memory, while TPM2 mRNA and protein expression increased after
      spatial training. Among the TPM2 mutations associated with skeletal myopathies,
      the TPM2E122K mutation was found to reduce TPM2 expression and impair spatial
      learning and memory in rats. CONCLUSIONS: We have identified a novel role of
      Smad4 SUMOylation and TPM2 in learning and memory formation. These results
      suggest that patients with skeletal myopathies who carry the TPM2E122K mutation
      may also have deficits in learning and memory functions.

PMID- 29183318
TI  - The development, implementation and evaluation of clinical pathways for chronic
      obstructive pulmonary disease (COPD) in Saskatchewan: protocol for an interrupted
      times series evaluation.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has substantial economic
      and human costs; it is expected to be the third leading cause of death worldwide
      by 2030. To minimize these costs high quality guidelines have been developed.
      However, guidelines alone rarely result in meaningful change. One method of
      integrating guidelines into practice is the use of clinical pathways (CPWs). CPWs
      bring available evidence to a range of healthcare professionals by detailing the
      essential steps in care and adapting guidelines to the local context.
      METHODS/DESIGN: We are working with local stakeholders to develop CPWs for COPD
      with the aims of improving care while reducing utilization. The CPWs will employ
      several steps including: standardizing diagnostic training, unifying components
      of chronic disease care, coordinating education and reconditioning programs, and
      ensuring care uses best practices. Further, we have worked to identify evidence
      informed implementation strategies which will be tailored to the local context.
      We will conduct a three-year research project using an interrupted time series
      (ITS) design in the form of a multiple baseline approach with control groups. The
      CPW will be implemented in two health regions (experimental groups) and two
      health regions will act as controls (control groups). The experimental and
      control groups will each contain an urban and rural health region. Primary
      outcomes for the study will be quality of care operationalized using hospital
      readmission rates and emergency department (ED) presentation rates. Secondary
      outcomes will be healthcare utilization and guideline adherence, operationalized
      using hospital admission rates, hospital length of stay and general practitioner
      (GP) visits. Results will be analyzed using segmented regression analysis.
      DISCUSSION: Funding has been procured from multiple stakeholders. The project has
      been deemed exempt from ethics review as it is a quality improvement project.
      Intervention implementation is expected to begin in summer of 2017. This project
      is expected to improve quality of care and reduce healthcare utilization. In
      addition it will provide evidence on the effects of CPWs in both urban and rural
      settings. If the CPWs are found effective we will work with all stakeholders to
      implement similar CPWs in surrounding health regions. TRIAL REGISTRATION:
      Clinicaltrials.gov ( NCT03075709 ). Registered 8 March 2017.

PMID- 29183319
TI  - PPARalpha is essential for retinal lipid metabolism and neuronal survival.
AB  - BACKGROUND: Peroxisome proliferator activated receptor-alpha (PPARalpha) is a
      ubiquitously expressed nuclear receptor. The role of endogenous PPARalpha in
      retinal neuronal homeostasis is unknown. Retinal photoreceptors are the highest
      energy-consuming cells in the body, requiring abundant energy substrates.
      PPARalpha is a known regulator of lipid metabolism, and we hypothesized that it
      may regulate lipid use for oxidative phosphorylation in energetically demanding
      retinal neurons. RESULTS: We found that endogenous PPARalpha is essential for the
      maintenance and survival of retinal neurons, with Pparalpha -/- mice developing
      retinal degeneration first detected at 8 weeks of age. Using extracellular flux
      analysis, we identified that PPARalpha mediates retinal utilization of lipids as
      an energy substrate, and that ablation of PPARalpha ultimately results in retinal
      bioenergetic deficiency and neurodegeneration. This may be due to PPARalpha
      regulation of lipid transporters, which facilitate the internalization of fatty
      acids into cell membranes and mitochondria for oxidation and ATP production.
      CONCLUSION: We identify an endogenous role for PPARalpha in retinal neuronal
      survival and lipid metabolism, and furthermore underscore the importance of fatty
      acid oxidation in photoreceptor survival. We also suggest PPARalpha as a putative
      therapeutic target for age-related macular degeneration, which may be due in part
      to decreased mitochondrial efficiency and subsequent energetic deficits.

PMID- 29183320
TI  - Fungal 7-epi-10-deacetyltaxol produced by an endophytic Pestalotiopsis microspora
      induces apoptosis in human hepatocellular carcinoma cell line (HepG2).
AB  - BACKGROUND: Paclitaxel (taxol) is a potent anticancer drug that is used in the
      treatment of a wide variety of cancerous. In the present study, we identified a
      taxol derivative named 7-epi-10-deacetyltaxol (EDT) from the culture of an
      endophytic fungus Pestalotiopsis microspora isolated from the bark of Taxodium
      mucronatum. This study was carried out to investigate the effects of fungal EDT
      on cell proliferation, the induction of apoptosis and the molecular mechanisms of
      apoptosis in human hepatoma HepG2 cells in vitro. METHODS: The endophytic fungus
      was identified by traditional and molecular taxonomical characterization and the
      fungal EDT was purified using column chromatography and confirmed by various
      spectroscopic and chromatographic comparisons with authentic paclitaxel. We
      studied the in vitro effects of EDT on HepG2 cells for parameters such as cell
      cycle distribution, DNA fragmentation, reactive oxygen species (ROS) generation
      and nuclear morphology. Further, western blot analysis was used to evaluate Bcl-2
      associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), p38-mitogen activated
      protein kinase (MAPK) and poly [ADP-ribose] polymerase (PARP) expression.
      RESULTS: We demonstrate that the fungal EDT exhibited significant in vitro
      cytotoxicity in HepG2 cells. We investigated cytotoxicity mechanism of EDT in
      HepG2 cells. The results showed nuclear condensation and DNA fragmentation were
      observed in cells treated with fungal EDT. Besides, the fungal EDT arrested HepG2
      cells at G2/M phase of cell cycle. Furthermore, fungal EDT induced apoptosis in
      HepG2 cells in a dose-dependent manner associated with ROS generation and
      increased Bax/Bcl-2 ratio, p38 MAPKs and PARP cleavage. CONCLUSIONS: Our data
      show that EDT induced apoptotic cell death in HepG2 cells occurs through
      intrinsic pathway by generation of ROS mediated and activation of MAPK pathway.
      This is the first report for 7-epi-10-deacetyltaxol (EDT) isolated from a
      microbial source.

PMID- 29183321
TI  - Effects of controlled hypoxemia or hypovolemia on global and intestinal
      oxygenation and perfusion in isoflurane anesthetized horses receiving an alpha-2
      agonist infusion.
AB  - BACKGROUND: Aim of this prospective experimental study was to assess effects of
      systemic hypoxemia and hypovolemia on global and gastrointestinal oxygenation and
      perfusion in anesthetized horses. Therefore, we anesthetized twelve systemically
      healthy warmblood horses using either xylazine or dexmedetomidine for
      premedication and midazolam and ketamine for induction. Anesthesia was maintained
      using isoflurane in oxygen with either xylazine or dexmedetomidine and horses
      were ventilated to normocapnia. During part A arterial oxygen saturation (SaO2)
      was reduced by reducing inspiratory oxygen fraction in steps of 5%. In part B
      hypovolemia was induced by controlled arterial exsanguination via roller pump
      (rate: 38 ml/kg/h). Mean arterial blood pressure (MAP), heart rate, pulmonary
      artery pressure, arterial and central venous blood gases and cardiac output were
      measured, cardiac index (CI) was calculated. Intestinal microperfusion and
      oxygenation were measured using laser Doppler flowmetry and white-light
      spectrophotometry. Surface probes were placed via median laparotomy on the
      stomach, jejunum and colon. RESULTS: Part A: Reduction in arterial oxygenation
      resulted in a sigmoid decrease in central venous oxygen partial pressure. At SaO2
      < 80% no further decrease in central venous oxygen partial pressure occurred.
      Intestinal oxygenation remained unchanged until SaO2 of 80% and then decreased.
      Heart rate and pulmonary artery pressure increased significantly during
      hypoxemia. Part B: Progressive reduction in circulating blood volume resulted in
      a linear decrease in MAP and CI. Intestinal perfusion was preserved until blood
      loss resulted in MAP and CI lower 51 +/- 5 mmHg and 40 +/- 3 mL/kg/min,
      respectively, and then decreased rapidly. CONCLUSIONS: Under isoflurane,
      intestinal tissue oxygenation remained at baseline when arterial oxygenation
      exceeded 80% and intestinal perfusion remained at baseline when MAP exceeded 51
      mmHg and CI exceeded 40 mL/kg/min in this group of horses. TRIAL REGISTRY NUMBER:
      33.14-42,502-04-14/1547.

PMID- 29183322
TI  - Extracts of Zuo Jin Wan, a traditional Chinese medicine, phenocopies 5-HTR1D
      antagonist in attenuating Wnt/beta-catenin signaling in colorectal cancer cells.
AB  - BACKGROUND: In vitro and in vivo studies have shown that Zuo Jin Wan (ZJW), a
      herbal formula of traditional Chinese medicine (TCM), possessed anticancer
      properties. However, the underlying mechanism for the action of ZJW remains
      unclear. Various subtypes of 5-Hydroxytryptamine receptor (5-HTR) have been shown
      to play a role in carcinogenesis and cancer metastasis. 5-HTR1D, among the
      subtypes, is highly expressed in colorectal cancer (CRC) cell lines and tissues.
      The present study aimed at investigating effect of ZJW extracts on the biological
      function of CRC cells, the expression of 5-HTR1D, and molecules of Wnt/beta
      catenin signaling pathway. METHODS: In this study, the effect of ZJW extracts on
      5-HTR1D expression and Wnt/beta-catenin signaling pathway were investigated and
      contrasted with GR127935 (GR), a known 5-HTR1D antagonist, using the CRC cell
      line SW403. The cells were respectively treated with GR127935 and different doses
      of ZJW extracts. Proliferation, apoptosis, migration, and invasion of SW403 cells
      were compared between ZJW and GR127935 treatments. The expression of 5-HTR1D and
      signaling molecules involved in the canonic Wnt/beta-catenin pathway were
      determined by Western blot analysis. RESULTS: After ZJW extracts treatment and
      GR127935 treatment, G1 arrest in cell cycle of SW403 was increased. Cell
      apoptosis was pronounced, and cell migration and invasion were suppressed. SW403
      cells showed a dose-dependently decreased expression of 5-HTR1D, meanwhile, beta
      catenin level was significantly decreased in nucleus of cells cultured with
      GR127935. Treatment of ZJW extracts dose-dependently resulted in decreased 5
      HTR1D and a concomitant reduction in the Wnt/beta-catenin signal transduction, an
      effect indistinguishable from GR127935 treatment. CONCLUSION: The anticancer
      activity of ZJW extracts may be partially achieved through attenuation of the 5
      HTR1D-Wnt/beta-catenin signaling pathway.

PMID- 29183323
TI  - Cervical metastasis of gingival carcinoma misdiagnosed as branchiogenic
      carcinoma, a rare entity - report of a case and review of literature.
AB  - BACKGROUND: A cervical cystic mass is associated with a number of pathologies
      that present with similar symptoms. These conditions are difficult to
      differentiate using fine-needle aspiration (FNA), ultrasound (US), computed
      tomography (CT) and magnetic resonance imaging (MRI). Another dilemma in the
      differential diagnosis of cervical cystic masses is due to the controversies
      associated with the existence of branchiogenic carcinoma (BC). BC is an extremely
      rare disease that must be differentiated from other conditions presenting with
      cervical cystic masses, especially cystic metastasis from occult primary lesions.
      CASE PRESENTATION: We present a case report of a right cervical cystic metastasis
      from a significantly small squamous cell carcinoma primary gingival lesion
      misdiagnosed as BC by histopathology. A 62-year-old female presented with a
      painless progressively enlarging cervical mass at the anterior edge of the
      sternocleidomastoid muscle in the right submandibular region. Preoperative MRI
      and US revealed a well-defined cystic round mass. Postoperative histological
      examination indicated BC. Positron emission tomography/computed tomography
      (PET/CT) revealed high 18F-FDG (18F 2-fluoro-2-deoxy-D-glucose) uptake in
      surgical regions with a SUV (standard uptake value) max 4.0 and ipsilateral
      nasopharynx with a SUVmax 4.4, without any distant metastasis. Pathologic results
      revealed nasopharyngeal lymphadenosis. Considering the low incidence of BC and
      the limitation of diagnosis in one institution, the patient was referred to
      another hospital. Physical examination detected a significantly small neoplasm
      (~3 mm diameter) in the right lower gingiva. Histopathological examination of the
      neoplasm revealed a well-differentiated squamous cell carcinoma. Surgery,
      including a partial mandibulectomy and modified neck dissection (neck level I-V
      and submental lymph nodes) were undertaken. Postoperative histopathological
      results revealed a well-differentiated squamous cell carcinoma of right lower
      gingiva and two metastatic lymph nodes in the 18 lymph nodes of level II. A month
      later, recurrence occurred in the right cervical level II. The patient was placed
      on postoperative concurrent chemo-radiotherapy and supportive care. The patient
      suffered from cachexia and survived for only six months after surgery.
      CONCLUSIONS: In cases of cervical cystic masses that appear after the age of 40,
      clinicians should bear in mind that occult primary lesions should be excluded and
      examination of the gingiva should be undertaken. PET/CT has a limited role in
      identifying small occult primary lesions and a comprehensive physical examination
      must be carefully performed.

PMID- 29183324
TI  - Novel essential amino acid supplements enriched with L-leucine facilitate
      increased protein and energy intakes in older women: a randomised controlled
      trial.
AB  - BACKGROUND: Inadequate protein intake (PI), containing a sub-optimal source of
      essential amino acids (EAAs), and reduced appetite are contributing factors to
      age-related sarcopenia. The satiating effects of dietary protein per se may
      negatively affect energy intake (EI), thus there is a need to explore alternative
      strategies to facilitate PI without compromising appetite and subsequent EI.
      METHODS: Older women completed two experiments (EXP1 and EXP2) where they
      consumed either a Bar (565 kJ), a Gel (477 kJ), both rich in EAAs (7.5 g, 40% L
      leucine), or nothing (Control). In EXP1, participants (n = 10, 68 +/- 5 years,
      mean +/- SD) consumed Bar, Gel or Control with appetite sensations and appetite
      related hormonal responses monitored for one hour, followed by consumption of an
      ad libitum breakfast (ALB). In EXP2, participants (n = 11, 69 +/- 5 years)
      ingested Bar, Gel or Control alongside an ALB. RESULTS: In EXP1, EI at ALB was
      not different (P = 0.674) between conditions (1179 +/- 566, 1254 +/- 511, 1206 +/
      550 kJ for the Control, Bar, and Gel respectively). However, total EI was
      significantly higher in the Bar and Gel compared to the Control after accounting
      for the energy content of the supplements (P < 0.0005). Analysis revealed
      significantly higher appetite Area under the Curve (AUC) (P < 0.007), a tendency
      for higher acylated ghrelin AUC (P = 0.087), and significantly lower pancreatic
      polypeptide AUC (P = 0.02) in the Control compared with the Bar and Gel. In EXP2,
      EI at ALB was significantly higher (P = 0.028) in the Control (1282 +/- 513 kJ)
      compared to the Bar (1026 +/- 565 kJ) and Gel (1064 +/- 495 kJ). However, total
      EI was significantly higher in the Bar and Gel after accounting for the energy
      content of the supplements (P < 0.007). CONCLUSIONS: Supplementation with either
      the Bar or Gel increased total energy intake whether consumed one hour before or
      during breakfast. This may represent an effective nutritional means for
      addressing protein and total energy deficiencies in older women. TRIAL
      REGISTRATION: Clinical trial register: retrospectively registered, ISRCTN12977929
      on.

PMID- 29183325
TI  - Prognostic significance of preoperative plasma D-dimer level in patients with
      surgically resected clinical stage I non-small cell lung cancer: a retrospective
      cohort study.
AB  - BACKGROUND: Plasma D-dimer level, a marker of hypercoagulation, has been reported
      to be associated with survival in several types of cancers. The present study
      aimed to evaluate the prognostic significance of preoperative D-dimer levels in
      patients with surgically resected clinical stage I non-small cell lung cancer
      (NSCLC). METHODS: Participants comprised 237 patients with surgically resected
      clinical stage I NSCLC. In addition to factors such as age, sex, and smoking
      status, the association between preoperative D-dimer level and survival was
      explored. RESULTS: Patients were divided into two groups according to D-dimer
      level: Group A, <= 1.0 MUg/ml (n = 170); and Group B, > 1.0 MUg/ml (n = 67). The
      5-year recurrence-free survival rate was 81.6% for Group A and 66.6% for Group B
      (p < 0.001). The 5-year overall survival rate was 93.6% for Group A and 84.7% for
      Group B (p = 0.002). Multivariate survival analysis identified D-dimer level as
      an independent prognostic factor, along with age, maximum standardized uptake
      value of the primary tumor, and pathological stage. CONCLUSIONS: Preoperative D
      dimer level is an independent prognostic factor in patients with surgically
      resected clinical stage I NSCLC.

PMID- 29183327
TI  - Seasonal malaria chemoprevention: successes and missed opportunities.
AB  - Seasonal malaria chemoprevention (SMC) was recommended in 2012 for young children
      in the Sahel during the peak malaria transmission season. Children are given a
      single dose of sulfadoxine/pyrimethamine combined with a 3-day course of
      amodiaquine, once a month for up to 4 months. Roll-out and scale-up of SMC has
      been impressive, with 12 million children receiving the intervention in 2016.
      There is evidence of its overall benefit in routine implementation settings, and
      a meta-analysis of clinical trial data showed a 75% decrease in clinical malaria
      compared to placebo. SMC is not free of shortcomings. Its target zone includes
      many hard-to-reach areas, both because of poor infrastructure and because of
      political instability. Treatment adherence to a 3-day course of preventive
      treatment has not been fully documented, and could prove challenging. As SMC is
      scaled up, integration into a broader, community-based paradigm which includes
      other preventive and curative activities may prove beneficial, both for health
      systems and for recipients.

PMID- 29183326
TI  - Ochrobactrum sp. MPV1 from a dump of roasted pyrites can be exploited as
      bacterial catalyst for the biogenesis of selenium and tellurium nanoparticles.
AB  - BACKGROUND: Bacteria have developed different mechanisms for the transformation
      of metalloid oxyanions to non-toxic chemical forms. A number of bacterial
      isolates so far obtained in axenic culture has shown the ability to bioreduce
      selenite and tellurite to the elemental state in different conditions along with
      the formation of nanoparticles-both inside and outside the cells-characterized by
      a variety of morphological features. This reductive process can be considered of
      major importance for two reasons: firstly, toxic and soluble (i.e. bioavailable)
      compounds such as selenite and tellurite are converted to a less toxic chemical
      forms (i.e. zero valent state); secondly, chalcogen nanoparticles have attracted
      great interest due to their photoelectric and semiconducting properties. In
      addition, their exploitation as antimicrobial agents is currently becoming an
      area of intensive research in medical sciences. RESULTS: In the present study,
      the bacterial strain Ochrobactrum sp. MPV1, isolated from a dump of roasted
      arsenopyrites as residues of a formerly sulfuric acid production near Scarlino
      (Tuscany, Italy) was analyzed for its capability of efficaciously bioreducing the
      chalcogen oxyanions selenite (SeO32-) and tellurite (TeO32-) to their respective
      elemental forms (Se0 and Te0) in aerobic conditions, with generation of Se- and
      Te-nanoparticles (Se- and TeNPs). The isolate could bioconvert 2 mM SeO32- and
      0.5 mM TeO32- to the corresponding Se0 and Te0 in 48 and 120 h, respectively. The
      intracellular accumulation of nanomaterials was demonstrated through electron
      microscopy. Moreover, several analyses were performed to shed light on the
      mechanisms involved in SeO32- and TeO32- bioreduction to their elemental states.
      Results obtained suggested that these oxyanions are bioconverted through two
      different mechanisms in Ochrobactrum sp. MPV1. Glutathione (GSH) seemed to play a
      key role in SeO32- bioreduction, while TeO32- bioconversion could be ascribed to
      the catalytic activity of intracellular NADH-dependent oxidoreductases. The
      organic coating surrounding biogenic Se- and TeNPs was also characterized through
      Fourier-transform infrared spectroscopy. This analysis revealed interesting
      differences among the NPs produced by Ochrobactrum sp. MPV1 and suggested a
      possible different role of phospholipids and proteins in both biosynthesis and
      stabilization of such chalcogen-NPs. CONCLUSIONS: In conclusion, Ochrobactrum sp.
      MPV1 has demonstrated to be an ideal candidate for the bioconversion of toxic
      oxyanions such as selenite and tellurite to their respective elemental forms,
      producing intracellular Se- and TeNPs possibly exploitable in biomedical and
      industrial applications.

PMID- 29183328
TI  - Initial psychometric validation of the questionnaire on pain caused by spasticity
      (QPS).
AB  - BACKGROUND: The Questionnaire on Pain caused by Spasticity (QPS) is a modular
      patient- and observer-reported outcome measure of spasticity-related pain (SRP)
      in children with cerebral palsy (CP). Originally developed for an English
      speaking population, we conducted a psychometric validation of a recently
      developed Chinese language version of the QPS. METHODS: This was a prospective,
      observational study involving 137 children/adolescents with CP and upper and/or
      lower limb spasticity and their parents at three sites in China. Six QPS modules
      were used, three each for upper and lower limb SRP assessment: a patient self
      report module; an interviewer-administered module used by site staff based on the
      cognitive, communicative, and motor abilities of a patient; and a
      parent/caregiver module administered for all children as an observer-reported
      outcome to complement the patient-reported outcome. If no assessment by the
      patient was possible because of age or cognitive impairments, only the
      parent/caregiver module was completed. Two visits with a 3-week interval provided
      data to evaluate and establish administrative ease of use, scoring of the QPS
      (factor analyses, Rasch analyses), reliability (Cronbach's alpha, intraclass
      correlation coefficient), validity (correlations with quality of life [PedsQLTM],
      motor impairment [Gross Motor Function Classification System, Gross Motor
      Function Measure-66, Manual Ability Classification System], and spasticity
      [Ashworth Scale, Modified Tardieu Scale]). RESULTS: For most children, clinic
      staff reported no difficulties associated with general QPS use or deciding which
      module to use. Children (and parents) who reported more demanding activities also
      reported higher levels of associated SRP (or observed SRP behavior). Activity
      related SRP items were combined for a total QPS score. Cronbach's alpha was low
      for child self-report, but was acceptable for interviewer-administered and parent
      reports on SRP. Test-retest reliability was high for all modules. Moderate-strong
      associations were frequently seen between QPS and quality of life, and were
      particularly strong in the child self-report group. Relatively weak associations
      were observed between QPS and motor impairment and spasticity. CONCLUSIONS: This
      first study was successful in providing initial evidence for the psychometric
      properties. Clinic staff were able to administer the QPS modules easily, and both
      children and parents were able to complete the designated QPS appropriately.

PMID- 29183329
TI  - Surface display of ACC deaminase on endophytic Enterobacteriaceae strains to
      increase saline resistance of host rice sprouts by regulating plant ethylene
      synthesis.
AB  - BACKGROUND: Most endophytic bacteria in consortia, which provide robust and broad
      metabolic capacity, are attractive for applications in plant metabolic
      engineering. The aim of this study was to investigate the effects of engineered
      endophytic bacterial strains on rice sprout ethylene level and growth under
      saline stress. A protocol was developed to synthesize engineered strains by
      expressing bacterial 1-aminocyclopropane-1-carboxylate (ACC) deaminase gene on
      cells of endophytic Enterobacter sp. E5 and Kosakonia sp. S1 (denoted as E5P and
      S1P, respectively). RESULTS: Results showed that ACC deaminase activities of the
      engineered strains E5P and S1P were significantly higher than those of the wild
      strains E5 and S1. About 32-41% deaminase was expressed on the surface of the
      engineered strains. Compared with the controls without inoculation, inoculation
      with the wild and engineered strains increased the deaminase activities of
      sprouts. Inoculation with the engineered strains increased 15-21% more deaminase
      activities of sprouts than with the wild strains, and reduced the ethylene
      concentrations of sprouts more significantly than with wild strains (P < 0.05).
      Inoculation with the wild and engineered strains promoted the growth of sprouts,
      while the promoting effects were more profound with the engineered strains than
      with the wild strains. The engineered strains improved saline resistance of
      sprouts under salt concentrations from 10 to 25 g L-1. The engineered strains
      promoted longer roots and shoots than the wild strains under the salt stresses,
      indicating that the ACC deaminases on the endophytic bacterial cells could result
      in plant-produced ACC degradation and inhibit plant ethylene formation.
      CONCLUSIONS: The protocols of expressing enzymes on endophytic bacterial cells
      showed greater potentials than those of plant over-expressed enzymes to increase
      the efficiency of plant metabolic pathways.

PMID- 29183330
TI  - Conversion of xylan by recyclable spores of Bacillus subtilis displaying
      thermophilic enzymes.
AB  - BACKGROUND: The Bacillus subtilis spore has long been used to display antigens
      and enzymes. Spore display can be accomplished by a recombinant and a non
      recombinant approach, with the latter proved more efficient than the recombinant
      one. We used the non-recombinant approach to independently adsorb two
      thermophilic enzymes, GH10-XA, an endo-1,4-beta-xylanase (EC 3.2.1.8) from
      Alicyclobacillus acidocaldarius, and GH3-XT, a beta-xylosidase (EC 3.2.1.37) from
      Thermotoga thermarum. These enzymes catalyze, respectively, the endohydrolysis of
      (1-4)-beta-D-xylosidic linkages of xylans and the hydrolysis of (1-4)-beta-D
      xylans to remove successive D-xylose residues from the non-reducing termini.
      RESULTS: We report that both purified enzymes were independently adsorbed on
      purified spores of B. subtilis. The adsorption was tight and both enzymes
      retained part of their specific activity. When spores displaying either GH10-XA
      or GH3-XT were mixed together, xylan was hydrolysed more efficiently than by a
      mixture of the two free, not spore-adsorbed, enzymes. The high total activity of
      the spore-bound enzymes is most likely due to a stabilization of the enzymes
      that, upon adsorption on the spore, remained active at the reaction conditions
      for longer than the free enzymes. Spore-adsorbed enzymes, collected after the two
      step reaction and incubated with fresh substrate, were still active and able to
      continue xylan degradation. The recycling of the mixed spore-bound enzymes
      allowed a strong increase of xylan degradation. CONCLUSION: Our results indicate
      that the two-step degradation of xylans can be accomplished by mixing spores
      displaying either one of two required enzymes. The two-step process occurs more
      efficiently than with the two un-adsorbed, free enzymes and adsorbed spores can
      be reused for at least one other reaction round. The efficiency of the process,
      the reusability of the adsorbed enzymes, and the well documented robustness of
      spores of B. subtilis indicate the spore as a suitable platform to display
      enzymes for single as well as multi-step reactions.

PMID- 29183331
TI  - Four successful pregnancies in a patient with Fontan palliation and congenital
      heart disease: a case report.
AB  - BACKGROUND: Fontan is a palliative procedure in patients with single ventricle.
      Single ventricle supports systemic cardiac output and pulmonary blood flow is
      passively directed to the right pulmonary artery. Women with Fontan palliation
      are reported to have increased maternal risk during pregnancy. There are few
      reports of successful pregnancies in such cases. However data on these
      pregnancies is lacking, we consider this to be the first reported from kingdom of
      Saudi Arabia. CASE PRESENTATION: We present a 35-year-old woman from the Kingdom
      of Saudi Arabia who had Fontan surgery and who had four successful pregnancies
      and multiple miscarriages. She delivered live, low birth weight neonates.
      CONCLUSION: This report provides an anecdotal evidence that pregnancy can be
      tolerated in an adequate Fontan patient with successful outcomes.

PMID- 29183332
TI  - A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease
      patients.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic
      inflammation of the gastrointestinal tract that is associated with changes in the
      gut microbiome. Here, we sought to identify strain-specific functional correlates
      with IBD outcomes. METHODS: We performed metagenomic sequencing of monthly stool
      samples from 20 IBD patients and 12 controls (266 total samples). These were
      taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2.
      Differentially abundant species were identified using MaAsLin and strain-specific
      pangenome haplotypes were analyzed using PanPhlAn. RESULTS: We found a
      significantly higher abundance in patients of facultative anaerobes that can
      tolerate the increased oxidative stress of the IBD gut. We also detected
      dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co
      occurring with increased disease activity. We identified two distinct clades of
      R. gnavus strains, one of which is enriched in IBD patients. To study functional
      differences between these two clades, we augmented the R. gnavus pangenome by
      sequencing nine isolates from IBD patients. We identified 199 IBD-specific,
      strain-specific genes involved in oxidative stress responses, adhesion, iron
      acquisition, and mucus utilization, potentially conferring an adaptive advantage
      for this R. gnavus clade in the IBD gut. CONCLUSIONS: This study adds further
      evidence to the hypothesis that increased oxidative stress may be a major factor
      shaping the dysbiosis of the microbiome observed in IBD and suggests that R.
      gnavus may be an important member of the altered gut community in IBD.

PMID- 29183333
TI  - Severe inhibition of lipooligosaccharide synthesis induces TLR2-dependent
      elimination of Mycobacterium marinum from THP1-derived macrophages.
AB  - BACKGROUND: Although mycobacterial glycolipids are among the first-line molecules
      involved in host-pathogen interactions, their contribution in virulence remains
      incomplete. Mycobacterium marinum is a waterborne pathogen of fish and other
      ectotherms, closely related to Mycobacterium tuberculosis. Since it causes
      tuberculosis-like systemic infection it is widely used as a model organism for
      studying the pathogenesis of tuberculosis. It is also an occasional opportunistic
      human pathogen. The M. marinum surface-exposed lipooligosaccharides (LOS) are
      immunogenic molecules that participate in the early interactions with macrophages
      and modulate the host immune system. Four major LOS species, designated LOS-I to
      LOS-IV, have been identified and characterized in M. marinum. Herein, we
      investigated the interactions between a panel of defined M. marinum LOS mutants
      that exhibited various degrees of truncation in the LOS structure, and human
      derived THP-1 macrophages to address the potential of LOSs to act as pro- or
      avirulence factors. RESULTS: A moderately truncated LOS structure did not
      interfere with M. marinum invasion. However, a deeper shortening of the LOS
      structure was associated with increased entry of M. marinum into host cells and
      increased elimination of the bacilli by the macrophages. These effects were
      dependent on Toll-like receptor 2. CONCLUSION: We provide the first evidence that
      LOSs inhibit the interaction between mycobacterial cell wall ligands and
      appropriate macrophage pattern recognition receptors, affecting uptake and
      elimination of the bacteria by host phagocytes.

PMID- 29183334
TI  - Depressive symptoms following natural disaster in Korea: psychometric properties
      of the Center for Epidemiologic Studies Depression Scale.
AB  - BACKGROUND: Depressive symptoms have been recognized as one of the most frequent
      complaints among natural disaster survivors. One of the most frequently used self
      report measures of depressive symptoms is the Center for Epidemiologic Studies
      Depression Scale (CES-D). To our knowledge, no study has yet examined the factor
      structure, reliability, and validity of the CES-D in a sample of natural disaster
      survivors. Thus, the present study investigated the factor structure,
      reliability, and validity of a Korean language version of the CES-D (KCES-D) for
      natural disaster survivors. METHODS: We utilized two archived datasets collected
      independently for two different periods in 2008 in the same region of Korea (n =
      192 for sample 1; n = 148 for sample 2). Participants were survivors of
      torrential rains in the mid-eastern region of the Korean peninsula. For analysis,
      Samples 1 and 2 were merged (N = 340). Confirmatory factor analysis was performed
      to evaluate the one-factor model, the four-factor model, and the bi-factor
      models, as well as the second-order factor model. Composite reliability was
      computed to examine the internal consistency of the KCES-D total and subscale
      scores. Finally, Pearson's r was computed to examine the relationship between the
      KCES-D and the trauma-related measures. RESULTS: The four-factor model provided
      the best fit to the data among the alternatives. The KCES-D showed adequate
      internal consistency, except for the 'interpersonal difficulties' subscale. Also
      regarding concurrent validity, weak to moderate positive correlations were
      observed between the KCES-D and the trauma-related measures. CONCLUSIONS: The
      results support the four-factor model and indicate that the KCES-D has adequate
      psychometric properties for natural disaster survivors. If these findings are
      further confirmed, the KCES-D can be used as a useful, rapid, and inexpensive
      screening tool for assessing depressive symptoms in natural disaster survivors.

PMID- 29183335
TI  - Evaluating medical convenience in ethnic minority areas of Southwest China via
      road network vulnerability: a case study for Dehong autonomous prefecture.
AB  - BACKGROUND: Southwest China is home to more than 30 ethnic minority groups. Since
      most of these populations reside in mountainous areas, convenient access to
      medical services is an important metric of how well their livelihoods are being
      protected. METHODS: This paper proposes a medical convenience index (MCI) and
      computation model for mountain residents, taking into account various conditions
      including topography, geology, and climate. Data on road networks were used for
      comprehensive evaluation from three perspectives: vulnerability, complexity, and
      accessibility. The model is innovative for considering road network vulnerability
      in mountainous areas, and proposing a method of evaluating road network
      vulnerability by measuring the impacts of debris flows based on only links. The
      model was used to compute and rank the respective MCIs for settlements of each
      ethnic population in the Dehong Dai and Jingpo Autonomous Prefecture of Yunnan
      Province, in 2009 and 2015. Data on the settlements over the two periods were
      also used to analyze the spatial differentiation of medical convenience levels
      within the study area. RESULTS: The medical convenience levels of many
      settlements improved significantly. 80 settlements were greatly improved, while
      another 103 showed slight improvement.Areas with obvious improvement were
      distributed in clusters, and mainly located in the southwestern part of Yingjiang
      County, northern Longchuan County, eastern Lianghe County, and the region where
      Lianghe and Longchuan counties and Mang City intersect. CONCLUSIONS: Development
      of the road network was found to be a major contributor to improvements in MCI
      for mountain residents over the six-year period.

PMID- 29183336
TI  - Oncological outcome of complete response after neoadjuvant chemotherapy for
      breast conserving surgery: a systematic review and meta-analysis.
AB  - BACKGROUND: With limited sample sizes and single-institution designs, how
      complete response (CR) after neoadjuvant chemotherapy (NAC) influences breast
      conserving surgery (BCS) and its value in prognosis are not clear. METHODS: A
      systematic research review was conducted using electronic database. The rate of
      clinical complete response (cCR) in BCS after NAC and these pathological CR (PCR)
      and non-pCR BCS patients' local recurrence-free survival (LRFS), distance
      recurrence-free survival (DRFS), overall survival (OS), and disease-free survival
      (DFS) rates were collected. A pooled analysis was performed using a fixed or
      random effects model and a Q test to determine heterogeneity. RESULTS: Sixteen
      studies with a total of 4639 patients were included. The pooled data revealed
      that cCR patients compared with non-cCR patients had significantly higher rates
      of BCS, with a summary estimate odds ratios (OR) of 4.54 (95% CI 2.03-10.17). The
      pooled data revealed that BCS patients who achieved pCR after NAC had
      significantly lower rates of LRFS (RR = 0.59, 95% CI 0.38-0.92) and DRFS (RR =
      0.27, 95% CI 0.13-0.55). Better DFS (RR = 0.09, 95% CI 0.04-0.25) and OS (RR =
      0.36, 95% CI 0.03-3.90) were also seen, but OS was not significantly different.
      CONCLUSIONS: The rate of successful BCS is higher in the cCR group than in the
      non-cCR group, means cCR after NAC can encourage patients to receive BCS. The
      achievement of pCR after NAC in BCS patients was associated with a good prognosis
      in terms of LRFS and DRFS, but its value in DFS and OS requires further
      investigation.

PMID- 29183337
TI  - Unconscious physiological response of healthy volunteers to dynamic respiration
      synchronized couch motion.
AB  - BACKGROUND: Intrafractional motion can be a substantial uncertainty in precision
      radiotherapy. Conventionally, the target volume is expanded to account for the
      motion. Couch-tracking is an alternative, where the patient is moved to
      compensate for the tumor motion. However, the couch motion may influence the
      patient's stress and respiration behavior decreasing the couch-tracking
      effectiveness. METHODS: In total, 100 volunteers were positioned supine on a
      robotic couch, which moved dynamically and respiration synchronized. During the
      measurement, the skin conductivity, the heartrate, and the gaze location were
      measured indicating the volunteer's stress. Volunteers rated the subjective
      motion sickness using a questionnaire. The measurement alternated between static
      and tracking segments (three cycles), each 1 min long. RESULTS: The respiration
      amplitude showed no significant difference between tracking and static segments,
      but decreased significantly from the first to the last tracking segment (p <
      0.0001). The respiration frequency differed significantly between tracking and
      static segments (p < 0.0001), but not between the first and the last tracking
      segment. The physiological parameters and the questionnaire showed mild signals
      of stress and motion sickness. CONCLUSION: Generally, people tolerated the couch
      motions. The interaction between couch motion and the patient's breathing pattern
      should be considered for a clinical implementation. TRIAL REGISTRATION: The study
      was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national
      clinical trials portal ( SNCTP000001878 ) on June 20, 2016.

PMID- 29183338
TI  - Optimization of PCR conditions for amplifying an AT-rich amino acid transporter
      promoter sequence with high number of tandem repeats from Arabidopsis thaliana.
AB  - OBJECTIVE: The aim of the present study is to optimize the PCR conditions
      required to amplify the promoter sequence of an amino acid transporter having an
      AT-rich base composition with a high number of tandem repeats. RESULT: Results
      show that successful amplification can be achieved by performing a 2-step PCR at
      a lower extension temperature of 65  degrees C for an increased extension period
      of 1.5 min/kb, with MgCl2 concentration ranging from 2.5 to 3.0 mM. The results
      also suggest that the DNA concentration of about 25-30 ng/ul was essential to
      achieve this amplification.

PMID- 29183339
TI  - Effect of EMG-triggered neuromuscular electrical stimulation with bilateral arm
      training on hemiplegic shoulder pain and arm function after stroke: a randomized
      controlled trial.
AB  - BACKGROUND: Hemiplegic shoulder pain is a frequent complication after stroke,
      leading to limited use of the affected arm. Neuromuscular electrical stimulation
      (NMES) and transcutaneous electrical nerve stimulation (TENS) are two widely used
      interventions to reduce pain, but the comparative efficacy of these two
      modalities remains uncertain. The purpose of this research was to compare the
      immediate and retained effects of EMG-triggered NMES and TENS, both in
      combination with bilateral arm training, on hemiplegic shoulder pain and arm
      function of stroke patients. METHODS: A single-blind, randomized controlled trial
      was conducted at two medical centers. Thirty-eight patients (25 males and 13
      females, 60.75 +/- 10.84 years old, post stroke duration 32.68 +/- 53.07 months)
      who had experienced a stroke more than 3 months ago at the time of recruitment
      and hemiplegic shoulder pain were randomized to EMG-triggered NMES or TENS. Both
      groups received electrical stimulation followed by bilateral arm training 3 times
      a week for 4 weeks. The primary outcome measures included a vertical Numerical
      Rating Scale supplemented with a Faces Rating Scale, and the short form of the
      Brief Pain Inventory. The secondary outcome measures were the upper-limb subscale
      of the Fugl-Meyer Assessment, and pain-free passive shoulder range of motion. All
      outcomes were measured pretreatment, post-treatment, and at 1-month after post
      treatment. Two-way mixed repeated measures ANOVAs were used to examine treatment
      effects. RESULTS: Compared to TENS with bilateral arm training, the EMG-triggered
      NMES with bilateral arm training was associated with lower pain intensity during
      active and passive shoulder movement (P =0.007, P =0.008), lower worst pain
      intensity (P = 0.003), and greater pain-free passive shoulder abduction (P
      =0.001) and internal rotation (P =0.004) at follow-up. Both groups improved in
      pain at rest (P =0.02), pain interference with daily activities, the Fugl-Meyer
      Assessment, and pain-free passive shoulder flexion and external rotation post
      treatment (P < 0.001) and maintained the improvement at follow-up (P < 0.001),
      except for resting pain (P =0.08). CONCLUSIONS: EMG-triggered NMES with bilateral
      arm training exhibited greater immediate and retained effects than TENS with
      bilateral arm training with respect to pain and shoulder impairment for chronic
      and subacute stroke patients with hemiplegic shoulder pain. TRIAL REGISTRATION:
      NCT01913509 .

PMID- 29183340
TI  - Mapping outdoor habitat and abnormally small newborns to develop an ambient
      health hazard index.
AB  - BACKGROUND: The geography of where pregnant mothers live is important for
      understanding outdoor environmental habitat that may result in adverse birth
      outcomes. We investigated whether more babies were born small for gestational age
      or low birth weight at term to mothers living in environments with a higher
      accumulation of outdoor hazards. METHODS: Live singleton births from the Alberta
      Perinatal Health Program, 2006-2012, were classified according to birth outcome,
      and used in a double kernel density estimation to determine ratios of each
      outcome per total births. Individual and overlay indices of spatial models of 136
      air emissions and 18 land variables were correlated with the small for
      gestational age and low birth weight at term, for the entire province and sub
      provincially. RESULTS: There were 24 air substances and land sources correlated
      with both small for gestational age and low birth weight at term density ratios.
      On the provincial scale, there were 13 air substances and 2 land factors; sub
      provincial analysis found 8 additional air substances and 1 land source.
      CONCLUSION: This study used a combination of multiple outdoor variables over a
      large geographic area in an objective model, which may be repeated over time or
      in other study areas. The air substance-weighted index best identified where
      mothers having abnormally small newborns lived within areas of potential outdoor
      hazards. However, individual air substances and the weighted index provide
      complementary information.

PMID- 29183341
TI  - Kinetics and dissolution of intratracheally administered nickel oxide
      nanomaterials in rats.
AB  - BACKGROUND: The toxicokinetics of nanomaterials are an important factor in
      toxicity, which may be affected by slow clearance and/or distribution in the
      body. METHODS: Four types of nickel oxide (NiO) nanoparticles were single
      administered intratracheally to male F344 rats at three doses of 0.67-6.0 mg/kg
      body weight. The rats were sacrificed under anesthesia and the lung, thoracic
      lymph nodes, bronchoalveolar lavage fluid, liver, and other organs were sampled
      for Ni burden measurement 3, 28, and 91 days post-administration; Ni excretion
      was measured 6 and 24 h after administration. Solubility of NiO nanoparticles was
      determined using artificial lysosomal fluid, artificial interstitial fluid,
      hydrogen peroxide solution, pure water, and saline. In addition, macrophage
      migration to trachea and phagosome-lysosome-fusion rate constants were estimated
      using pulmonary clearance and dissolution rate constants. RESULTS: The wire-like
      NiO nanoparticles were 100% dissolved by 24 h when mixed with artificial
      lysosomal fluid (dissolution rate coefficient: 0.18/h); spherical NiO
      nanoparticles were 12% and 35% dissolved after 216 h when mixed with artificial
      lysosomal fluid (1.4 * 10-3 and 4.9 * 10-3/h). The largest irregular-shaped NiO
      nanoparticles hardly dissolved in any solution, including artificial lysosomal
      fluid (7.8 * 10-5/h). Pulmonary clearance rate constants, estimated using a one
      compartment model, were much higher for the NiO nanoparticles with a wire-shape
      (0.069-0.078/day) than for the spherical and irregular-shaped NiO nanoparticles
      (0-0.012/day). Pulmonary clearance rate constants of the largest irregular-shaped
      NiO nanoparticles showed an inverse correlation with dose. Translocation of NiO
      from the lungs to the thoracic lymph nodes increased in a time- and dose
      dependent manner for three spherical and irregular-shaped NiO nanoparticles, but
      not for the wire-like NiO nanoparticles. Thirty-five percent of the wire-like NiO
      nanoparticles were excreted in the first 24 h after administration; excretion was
      0.33-3.6% in that time frame for the spherical and irregular-shaped NiO
      nanoparticles. CONCLUSION: These findings suggest that nanomaterial solubility
      differences can result in variations in their pulmonary clearance. Nanoparticles
      with moderate lysosomal solubility may induce persistent pulmonary inflammation.

PMID- 29183342
TI  - The pH stability of foot-and-mouth disease virus.
AB  - : ?: This review summarized the molecular determinants of the acid stability of
      FMDV in order to explore the uncoating mechanism of FMDV and improve the acid
      stability of vaccines. BACKGROUND: The foot-and-mouth disease virus (FMDV) capsid
      is highly acid labile and tends to dissociate into pentameric subunits at acidic
      condition to release viral RNA for initiating virus replication. However, the
      acid stability of virus capsid is greatly required for the maintenance of intact
      virion during the process of virus culture and vaccine production. The conflict
      between the acid lability in vivo and acid stability in vitro of FMDV capsid
      promotes the selection of a series of amino acid substitutions which can confer
      resistance to acid-induced FMDV inactivation. In order to explore the uncoating
      activity of FMDV and enhance the acid stability of vaccines, we summarized the
      available works about the pH stability of FMDV. In this review, we analyzed the
      intrinsic reasons for the acid instability of FMDV from the structural and
      functional aspects. We also listed all substitutions obtained by different
      research methods and showed them in the partial capsid of FMDV. We found that a
      quadrangle region in the viral capsid was the place where a great many pH
      sensitive residues were distributed. As the uncoating event of FMDV is dependent
      on the pH-sensitive amino acid residues in the capsid, this most pH-sensitive
      position indicates a potential candidate location for RNA delivery triggered by
      the acid-induced coat disassociation. SHORT CONCLUSION: This review provided an
      overview of the pH stability of FMDV. The study of pH stability of FMDV not only
      contributes to the exploration of molecule and mechanism information for FMDV
      uncoating, but also enlightens the development of FMDV vaccines, including the
      traditionally inactivated vaccines and the new VLP (virus-like particle)
      vaccines.

PMID- 29183343
TI  - Primary and metastatic cardiac tumors: echocardiographic diagnosis, treatment and
      prognosis in a 15-years single center study.
AB  - BACKGROUND: The frequency of primary cardiac tumors is rare at about 0.3% by
      autopsy. Our objective was to investigate the characteristics and locations of
      cardiac tumors and to provide a prognostic analysis in our hospital. METHODS: We
      collected data on 95 patients with echocardiographic diagnosis or detection of
      cardiac tumors in a prospective analysis from 1999 to 2014. The median follow-up
      period was 43 months (0.5-183 months). RESULTS: The subjects included 56 men and
      39 women with a mean age of 65 years. Clinical diagnosis revealed primary tumors
      in 61 patients (64%) and secondary metastatic tumors in 34 patients (36%). In the
      61 patients, 41 patients (67%) underwent surgery and tissue samples were
      obtained. Of these 41 patients, benign tumors were found in 30 cases (73%). One
      patient (2%) was diagnosed with thrombus. Among the benign tumors, myxoma (67%)
      was the most common type followed by papillary fibroelastoma (23%). The most
      common site was the left atrium (35%) followed by the right atrium (25%). Primary
      malignant tumors were diagnosed in 10 cases (24%), including 6 angiosarcomas, 3
      lymphomas, and 1 leiomyosarcoma. The diagnostic accuracy of echocardiography was
      80%. The patients with benign tumors were all alive at the end of the follow-up
      period. In contrast, 7 patients with malignant tumors died (70%) (p < 0.0001).
      CONCLUSIONS: Our data is in line with previous literature. Our study also
      suggests the necessity of extending our knowledge of the characteristics of
      cardiac tumors for diagnosis.

PMID- 29183344
TI  - Oral verruciform xanthoma and erythroplakia associated with chronic graft-versus
      host disease: a rare case report and review of the literature.
AB  - BACKGROUND: Oral verruciform xanthoma is an uncommon benign lesion. Although oral
      verruciform xanthoma occurs in healthy individuals, it has been also reported in
      association with some inflammatory conditions. The aim of this study is to report
      a case of oral verruciform xanthoma associated with chronic graft-versus-host
      disease and to review the literature on this topic. CASE PRESENTATION: A 47-year
      old Caucasian male presented to the Sector of Oral Medicine "V. Margiotta",
      University Policlinic "P. Giaccone" of Palermo complaining of a mass on the
      gingiva. He first noticed the painless mass 1 year ago. He reported to have
      undergone allogenic hematopoietic stem cell transplantation 15 years ago for
      acute lymphoblastic leukaemia. Intraoral examination revealed a well
      circumscribed, sessile yellowish and verrucous nodule upon canine, multiple
      yellowish and verrucous nodules on the hard palate, yellowish and verrucous
      nodules on left buccal mucosa. In addiction an area of white striae in a
      reticular pattern with erythema and ulceration was present on the dorsum of the
      tongue. This lesion was consistent with a known history of oral chronic graft
      versus host disease. Moreover, we observed a suspected area of oral erythroplakia
      yet on the dorsum of the tongue. In biopsy specimen of hard palate
      histopathological examination revealed a diagnosis of verrucous xanthoma of the
      oral cavity; in addiction in biopsy specimen of the dorsum of the tongue revealed
      the presence of erythroplakia with high grade dysplasia. CONCLUSION: Verruciform
      xanthoma of the oral cavity associated with chronic graft-versus-host disease is
      a rare condition with a usually benign clinical course but malignant
      transformation has been described in association with oral potential malignant
      disorder (e.g. chronic graft versus host disease, erythroplakia). Very rare cases
      showed association with oral chronic graft versus-host-disease. To date, only
      eight cases were published in the world literature. Therefore it could be
      important follow up patients also for oral verruciform xanthoma onset.

PMID- 29183345
TI  - Primary tracheal schwannoma a review of a rare entity: current understanding of
      management and followup.
AB  - BACKGROUND: Neurogenic tumors of the tracheobronchial tree are extremely rare and
      include neurofibroma and schwannoma. We report a case of primary recurrent
      tracheal schwannoma causing obstructive airway symptoms. CASE PRESENTATION: A 60
      year-old man presented with obstructive airway symptoms due to recurrent tracheal
      schwannoma. Due the recurrence, size of the tumor and low surgical risk, the
      patient was treated with tracheal resection. CONCLUSION: Primary endotracheal
      neurogenic tumors are extremely rare, but one should consider them in the
      differential diagnosis of persistent upper airway symptoms. While endoscopic
      therapies recur nearly a quarter of the time, surgical resections do not have any
      recorded recurrences.

PMID- 29183346
TI  - ALX4, an epigenetically down regulated tumor suppressor, inhibits breast cancer
      progression by interfering Wnt/beta-catenin pathway.
AB  - BACKGROUND: ALX4 is a paired-like homedomain transcription factor mainly
      expressed in the mesenchymal compartment of variety of developing tissues, but
      its functions, regulation mechanisms and clinical values in breast cancer remains
      unclear. METHODS: The expression of ALX4 in breast cancer cell lines and
      patients' tissues were detected by RT-PCR, qPCR and western blot. Furthermore
      TCGA database was applied to confirm these results. MSP and BSP methods were used
      to assess the methylation of ALX4 promoter region. In vitro proliferation,
      metastasis and in vivo nude mice model were used to evaluate the anti-tumor
      effect of ALX4 on breast cancer cell lines. Luciferase reporter assay, western
      blot and TCGA database were used to investigate the tumor suppression mechanisms
      of ALX4. TMA of 142 breast patients was generated to evaluate the clinical
      significance of ALX4. RESULTS: Expression analysis revealed that ALX4 expression
      is down regulated in breast cancer cell lines and tissues. MSP study showed that
      the promoter region of ALX4 was hyper-methylated 100% (3/3) in breast cancer cell
      lines and 69.44% (75/108) in primary breast tumors tissues while 0% (0/8) in
      normal breast tissues. 5-aza-dc de-methylation treatment restored ALX4 expression
      in breast cancer cell lines. Functional studies showed that ectopic expression of
      ALX4 in breast cancer cells inhibited cell proliferation, metastasis in vitro and
      in vivo. Mechanism study found that ALX4 exerted its anti-tumor function by
      suppressing the Wnt/beta-catenin pathway through promoting the phosphorylation
      degradation of beta-catenin in a GSK3beta dependent manner. Clinically
      multivariate analysis showed that ALX4 expression was an independent favorable
      prognostic factor in breast cancer patients. CONCLUSIONS: We reveal for the first
      time that ALX4 acts as a novel functional tumor suppressor inactivated by DNA
      methylation and is an independent prognostic factor in breast cancer.

PMID- 29183348
TI  - Influence of breast compression pressure on the performance of population-based
      mammography screening.
AB  - BACKGROUND: In mammography, breast compression is applied to reduce the thickness
      of the breast. While it is widely accepted that firm breast compression is needed
      to ensure acceptable image quality, guidelines remain vague about how much
      compression should be applied during mammogram acquisition. A quantitative
      parameter indicating the desirable amount of compression is not available.
      Consequently, little is known about the relationship between the amount of breast
      compression and breast cancer detectability. The purpose of this study is to
      determine the effect of breast compression pressure in mammography on breast
      cancer screening outcomes. METHODS: We used digital image analysis methods to
      determine breast volume, percent dense volume, and pressure from 132,776
      examinations of 57,179 women participating in the Dutch population-based biennial
      breast cancer screening program. Pressure was estimated by dividing the
      compression force by the area of the contact surface between breast and
      compression paddle. The data was subdivided into quintiles of pressure and the
      number of screen-detected cancers, interval cancers, false positives, and true
      negatives were determined for each group. Generalized estimating equations were
      used to account for correlation between examinations of the same woman and for
      the effect of breast density and volume when estimating sensitivity, specificity,
      and other performance measures. Sensitivity was computed using interval cancers
      occurring between two screening rounds and using interval cancers within 12
      months after screening. Pair-wise testing for significant differences was
      performed. RESULTS: Percent dense volume increased with increasing pressure,
      while breast volume decreased. Sensitivity in quintiles with increasing pressure
      was 82.0%, 77.1%, 79.8%, 71.1%, and 70.8%. Sensitivity based on interval cancers
      within 12 months was significantly lower in the highest pressure quintile
      compared to the third (84.3% vs 93.9%, p = 0.034). Specificity was lower in the
      lowest pressure quintile (98.0%) compared to the second, third, and fourth group
      (98.5%, p < 0.005). Specificity of the fifth quintile was 98.4%. CONCLUSION:
      Results suggest that if too much pressure is applied during mammography this may
      reduce sensitivity. In contrast, if pressure is low this may decrease
      specificity.

PMID- 29183347
TI  - The effect of an intensive smoking cessation intervention on disease activity in
      patients with rheumatoid arthritis: study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory rheumatic
      disease with the potential to induce significant disability. Patients with RA are
      at increased risk of cardiovascular diseases (CVD). Smokers with RA tend to
      experience more pain and fatigue, higher disease activity, more erosive joint
      destruction and a lower health-related quality of life (HR-QoL) than non-smokers.
      It remains to be determined whether these effects can be reduced by smoking
      cessation. This randomised controlled trial (RCT) in patients with RA aims to
      examine the effect of intensive smoking cessation intervention (motivational
      counselling combined with tailored nicotine replacement therapy) versus standard
      care on smoking cessation, and consequently on disease activity. Secondary
      objectives are to explore the effect on flare, risk factors for CVD, lung
      function, physical function, HR-QoL, pain and fatigue in patients with RA.
      METHODS: This will be a multicentre, open label, two arm, parallel group, RCT,
      including 150 daily smokers with RA, being in remission or having low-moderate
      disease activity (DAS28 <= 5.1). The intervention group (n = 75) will receive
      five counselling sessions with a trained smoking cessation counsellor based on
      the principles of motivational counselling. Furthermore, intervention patients
      will be offered nicotine replacement therapy tailored to individual needs.
      Participants randomised to the control group will receive standard care. The co
      primary outcome is a hierarchical endpoint, which will be evaluated at 3 months
      follow-up and will include (1) self-reported smoking cessation biochemically
      validated by exhaled carbon monoxide and (2) achievement of EULAR clinical
      response (an improvement in DAS28 of > 0.6). Follow-up visits will be performed
      at 3, 6 and 12 months post-intervention. DISCUSSION: This trial will reveal
      whether intensive smoking cessation counselling helps smokers with RA to achieve
      continuous smoking cessation and whether, as a concomitant benefit, it will
      reduce their RA disease activity. The trial aims to generate high quality
      evidence for the feasibility of a health promotion intervention for smokers with
      RA. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02901886 . Registered
      on 10 September 2016. Recruitment status updated on 10th October 2016.

PMID- 29183349
TI  - A Drosophila genetic model of nephrolithiasis: transcriptional changes in
      response to diet induced stone formation.
AB  - BACKGROUND: Urolithiasis is a significant healthcare issue but the
      pathophysiology of stone disease remains poorly understood. Drosophila Malpighian
      tubules were known to share similar physiological function to human renal
      tubules. We have used Drosophila as a genetic model to study the transcriptional
      response to stone formation secondary to dietary manipulation. METHODS: Wild-type
      male flies were raised on standard medium supplemented with lithogenic agents:
      control, sodium oxalate (NaOx) and ethylene glycol (EG). At 2 weeks, Malpighian
      tubules were dissected under polarized microscope to visualize crystals. The
      parallel group was dissected for RNA extraction and subsequent next-generation
      RNA sequencing. RESULTS: Crystal formation was visualized in 20%(+/-2.2) of flies
      on control diet, 73%(+/-3.6) on NaOx diet and 84%(+/-2.2) on EG diet.
      Differentially expressed genes were identified in flies fed with NaOx and EG diet
      comparing with the control group. Fifty-eight genes were differentially expressed
      (FDR <0.05, p < 0.05) in NaOx diet and 20 genes in EG diet. The molecular
      function of differentially expressed genes were assessed. Among these, Nervana 3,
      Eaat1 (Excitatory amino acid transporter 1), CG7912, CG5404, CG3036 worked as ion
      transmembrane transporters, which were possibly involved in stone pathogenesis.
      CONCLUSIONS: We have shown that by dietary modification, stone formation can be
      manipulated and visualized in Drosophila Malpighian tubules. This genetic model
      could be potentially used to identify the candidate genes that influence stone
      risk hence providing more insight to the pathogenesis of human stone disease.

PMID- 29183350
TI  - Sequential activation of the AKT pathway in human osteoblasts treated with
      Oscarvit: a bioactive product with positive effect both on skeletal pain and
      mineralization in osteoblasts.
AB  - BACKGROUND: Oscarvit (OSC) is an in-house preparation consisting of calcium,
      magnesium, phosphorus, strontium, Vitamin D, and eggshell membrane hydrolysate
      containing naturally occurring glycosaminoglycans and sulfated glycoproteins. OSC
      has been used both in an open-label human study and in vitro in osteoblasts.
      METHODS: Fifteen patients divided into three groups received oral OSC 0.6 g three
      times daily for 20 days. The main outcome measures were regional skeletal pain
      over the treatment period. For the in vitro experiments eight primary human
      osteoblasts cultures were established from trabecular bone, six of them from the
      femoral head, and two from the tibia. Cells were cultured for five to 20 days in
      the presence of 20 MUg/ml OSC. Immunocytochemistry and RT-PCR were used to detect
      molecular alterations involved in the mineralization process. Calcium
      concentration was measured by means of a colorimetric assay and cell viability
      was analyzed using the LDH cytotoxicity assay. To investigate whether the
      osteoblasts response to OSC is associated with signaling processes the ERK1/2 and
      AKT signal transduction pathways were analyzed. RESULTS: Open label human study:
      OSC, 0.6 g three times daily, resulted in a significant positive effect on pain
      alleviation of 42% after 5 days (p < 0.001), 57% after 10 days and 68% after 20
      days (p < 0.0001; for both time points), with no side-effects being reported. In
      vitro analysis: In osteoblasts, growing in OSC-supplemented media significant
      overexpression of bone gamma-carboxylglutamic acid-containing protein, secreted
      phosphoprotein-1, integrin binding sialoprotein, and dentin matrix phosphoprotein
      genes could be detected when compared to control osteoblasts grown in the absence
      of OSC. Moreover, OSC-treated osteoblasts produced over the study period vast
      extracellular calcium deposits without any loss of cellular integrity or signs of
      cellular toxicity. In addition OSC promotes osteoblast differentiation and
      activates the AKT signaling pathway. CONCLUSION: This open label study provides
      preliminary evidence of the efficacy of OSC. Despite the limitations (small
      heterogeneous patient group) the findings can be viewed as a necessary
      investigation that supports further clinical trials with a double-blind
      controlled design. Experiments at cellular and molecular level provide
      supplementary information about OSC that increases mineralization in osteoblasts
      and activation of the AKT pathway. TRIAL REGISTRATION: DRKS00013233 , 06th
      November 2017, retrospectively registered.

PMID- 29183351
TI  - Thyroid gland hemorrhage after blunt neck trauma: case report and review of the
      literature.
AB  - BACKGROUND: Thyroid hemorrhage is considered to be an uncommon complication
      following blunt trauma to the neck. This condition is potentially life
      threatening due to airway compression and may therefore require emergency airway
      management and surgical intervention in some cases. CASE PRESENTATION: We present
      the case of a 52-year-old woman who experienced a traumatic thyroid gland rupture
      (right lobe) with subsequent active arterial bleeding from branches of the
      inferior thyroid artery. On the same day, the patient presented to our emergency
      department with a painful swelling of the neck with an inspiratory stridor and
      hoarseness a few hours after a cycling accident. A right hemithyroidectomy was
      performed. The postoperative course was uneventful. We identified 33 additional
      cases published in English literature within the last 30 years, reporting blunt
      trauma to the neck with hemorrhagic complication of the thyroid gland. We provide
      a systematic review and particularly consider the aspects of endocrine surgery.
      CONCLUSION: The treatment approach for patients with blunt thyroid trauma should
      be dependent on the extent of the thyroid injury. Patients with tracheal
      compression, active bleeding and increasing hoarseness/shortness of breath
      require emergency airway control and often surgical exploration for hemorrhage
      control followed by resection of the ruptured thyroid. Importantly, in contrast
      to routine thyroid surgery, no electromyographic endotracheal tube is used during
      emergency intubation. Exchange of an endotracheal tube should be carefully
      evaluated due to difficult airway management in this setting. For protection
      against double-sided recurrent nerve palsy and postoperative hypoparathyroidism,
      a unilateral approach is preferable whenever possible.

PMID- 29183353
TI  - Comparison of the clinical and microbiological characteristics of Campylobacter
      and Helicobacter bacteremia: the importance of time to blood culture positivity
      using the BACTEC blood culture systems.
AB  - OBJECTIVE: Campylobacter spp. and Helicobacter spp. are rare but important causes
      of bacteremia in humans. Distinguishing these bacteria is complicated because of
      their similar phenotypic profiles. We conducted clinical and microbiological
      investigations of Campylobacter spp. or Helicobacter spp. bacteremia. Patients
      diagnosed with bacteremia from 2008 to 2014 were included. The clinical and
      microbiological characteristics of Campylobacter spp. and Helicobacter spp.
      bacteremia were compared. The BACTEC system was used in blood cultures. A
      receiver operating characteristic curve was plotted based on the time to blood
      culture positivity. RESULTS: Sixteen cases of Helicobacter spp. bacteremia
      (patient age: 61 +/- 18 years) and 14 cases of Campylobacter spp. bacteremia
      (patient age: 49 +/- 21 years) were identified. Median time to blood culture
      positivity was longer for the Helicobacter spp. cases than the Campylobacter spp.
      cases (91.4 h vs 55.3 h, p < 0.01). A time to blood culture positivity > 75 h
      predicted Helicobacter spp. bacteremia with a sensitivity of 0.88 and a
      specificity of 0.93 (area under the receiver operating characteristic curve of
      0.90). In conclusion, a time to blood culture positivity was useful in
      distinguishing Helicobacter spp. bacteremia from Campylobacter spp. bacteremia.

PMID- 29183352
TI  - Risk factors for difficulty of laparoscopic cholecystectomy in grade II acute
      cholecystitis according to the Tokyo guidelines 2013.
AB  - BACKGROUND: The Tokyo Guidelines 2013 classifies acute cholecystitis (AC) into
      three grades and recommends appropriate therapy for each grade. For grade II AC,
      either early laparoscopic cholecystectomy (LC) or percutaneous transhepatic
      gallbladder drainage (PTGBD) should be performed. This study aimed to identify
      the risk factors for difficulty of LC for treating grade II AC. METHODS: Totally,
      122 patients who underwent LC for grade II AC were enrolled and divided into
      difficult LC (DLC) and nondifficult LC (NDLC) groups. The DLC group included
      patients who experienced one of the following conditions: conversion from LC to
      open cholecystectomy, operating time >= 180 min, or blood loss >=300 ml.
      Preoperative characteristics and postoperative outcomes were analyzed. RESULTS:
      In univariate analysis, risk factors included male sex, interval between symptom
      onset and admission, interval between symptom onset and LC, and anticoagulant
      therapy. The incidence of postoperative complications was higher in the DLC group
      than in the NDLC group (23.5% vs. 4.6%, p = 0.0016). According to receiver
      operating characteristic curves, the optimal cutoff value was calculated, and
      multivariate analysis showed that male sex [odds ratio (OR), 5.76; 95% confidence
      interval (CI), 1.979-19.51; p = 0.0009) and interval between symptom onset and LC
      of over 96 h (OR, 6.32; 95% CI, 2.126-20.15; p = 0.0009) were independent risk
      factors for difficulty of LC. CONCLUSIONS: In patients with grade II AC, LC was
      technically difficult when performed over 96 h after symptom onset. Moreover,
      male sex was a risk factor. Therefore, PTGBD should be considered in these
      patients.

PMID- 29183354
TI  - Motives for change of first-line antiretroviral therapy regimens in an unselected
      cohort of HIV/AIDS patients at a major referral centre in South-west Cameroon.
AB  - OBJECTIVE: The rapid scale-up of antiretroviral therapy (ART) coverage in sub
      Saharan Africa has encountered the challenge of maintaining international
      clinical standards of ART utilization and change of ART regimens. In Cameroon,
      scarce reports have documented the motives for change of ART. This study had as
      objective to investigate the reasons for switch in ART through a secondary
      analysis and descriptive synthesis of data from a cross-sectional study at the
      Limbe Regional Hospital. RESULTS: One hundred participants were included. Their
      mean age was 40.2 +/- 8.0 years and 70% of them were females. The median duration
      of ART use was 60 months. Zidovudine-Lamivudine-Nevirapine regimen was received
      by 83% of patients while the Stavudine-Lamivudine-Nevirapine regimen had the
      highest median duration of use (58 months). Most patients had experienced changes
      in ART (especially from Stavudine-Lamivudine-Nevirapine regimen) with the chief
      reason being unavailability of their previous regimens. Four patients had their
      ART changed due to active tuberculosis, 4 due to pregnancy and 7 due to ART
      toxicity (4 and 3 for peripheral neuropathy and lipodystrophy respectively). In
      conclusion, shortages in ART hugely influenced switch in regimens. In such a
      context, modifications in ART possibly deviate from guidelines with resultant sub
      optimal therapy and enhanced drug resistance.

PMID- 29183355
TI  - Intestinal parasitosis and anaemia among patients in a Health Center, North
      Ethiopia.
AB  - OBJECTIVE: The aim of this cross-sectional study was to determine the magnitude
      of intestinal parasitosis and anaemia in a Health Center, North Ethiopia.
      RESULTS: A total of 427 outpatients were enrolled and the median age of the
      participants was 22 years. The prevalence of intestinal parasitosis was 143
      (33.5%). Age, place of residence and occupation were significantly associated
      with intestinal parasitosis. When we see parasite specific factors, significant
      associations were observed for source of drinking water (P = 0.02), age (P <
      0.001) and family size (P = 0.003), respectively with Entameba histolytica,
      Hookworm and Giardia lamblia infections. The overall prevalence of anaemia was 35
      (8.2%). The mean haemoglobin concentration among the study participants was 12.8
      mg/dl. The highest prevalence of anemia was recorded for the age group of 15-19
      years (29.6%). The proportion of anemia among intestinal parasite -infected and
      non-infected participants was 10.7 and 7.0%, respectively. Study participants
      infected with S. stercoralis and hookworm were more likely to develop anaemia
      than the non- infected ones; AOR (adjusted odds ratio) = 5.3, 95% CI (1.01-27.4);
      P = 0.028 and AOR = 11.1, 95% CI (3.36-36.9); P = 0.000, respectively.

PMID- 29183356
TI  - Outcome of uncomplicated ureteric calculi managed with medical expulsive therapy
      in the outpatient clinic of a urology unit in Sri Lanka.
AB  - OBJECTIVE: Although medical expulsive therapy (MET) is shown to be effective for
      ureteric calculi, the optimum duration and the stone size suitable for MET are
      not well established yet. The objectives of the study were to determine the
      optimum duration and maximum stone size suitable for MET. RESULTS: All patients
      with radiologically confirmed uncomplicated ureteric calculi treated with MET
      using tamsulosin over a period of 6 months in the outpatient setting were
      followed up. There were 213 patients. 165 were men. Mean age was 42 years. At
      presentation 42 stones were in upper ureter (19.7%), 51 in mid ureter (23.9%),
      120 in lower ureter (56.3%). The majority (82.7%) of stones were less than 10 mm.
      Seven stones (3.3%) were over 15 mm. Ninety-two (43.2%) patients had spontaneous
      passage of stones within 6-weeks of MET. Another 38.9% passed the stone within
      the next 6-weeks. Thirty-eight patients (17.8%) required surgery. Uncomplicated
      ureteric stones up to 10 mm can be given a trial of MET using tamsulosin which
      can be extended up to 12-weeks with a success rate over 92%. This may have
      substantial clinical and fiscal benefits by reducing the number of interventional
      procedures especially in resource-poor settings.

PMID- 29183358
TI  - Bacteriological aspects of chronic osteoarticular infections in adults: the
      influence of the osteosynthesis material.
AB  - BACKGROUND: The aim of this study is to establish the bacterial epidemiology of
      chronic osteoarticular infections in adults, to study the susceptibility of the
      isolated strains to antibiotics and to demonstrate the influence of
      osteosynthesis material thereon. PATIENTS AND METHODS: This is a retrospective
      study of 78 months, from January 2006 to June 2012, providing bacteriological
      samples from patients with osteitis and osteoarthritis in the Mohammed V military
      teaching hospital of Rabat. Isolation and identification of bacteria were made by
      bacteriological classical techniques. The antimicrobial susceptibility testing of
      the isolates was performed by disk diffusion agar method, as recommended by the
      Committee of the susceptibility of the French Society for Microbiology (CA-SFM).
      RESULTS: We collected 234 cases, 53% (n = 124) of patients without osteosynthesis
      material (group A) and 47% (n = 110) patients with osteosynthesis material (group
      B).We isolated 371 bacteria which 51.49 (n = 191) in group A and 48.51% (n = 180)
      in group B. Gram-positive cocci were the most frequent (n = 234), followed by the
      Gram-negative bacilli (n = 114) and the Gram-positive bacilli (n = 19). Our study
      shows that the rate of resistance to antibiotics in strains obtained from
      patients with osteosynthesis material is higher compared to those obtained from
      patients without osteosynthesis material. CONCLUSIONS: Chronic OA infection in
      adults is difficult to diagnose and treat. Its good management must be
      multidisciplinary.

PMID- 29183357
TI  - Automated telephone interventions for problematic alcohol use in clinical and
      population samples: a randomized controlled trial.
AB  - OBJECTIVE: The primary objective was to evaluate 6-month outcomes for brief and
      extensive automated telephony interventions targeting problematic alcohol use, in
      comparison to an assessment-only control group. The secondary objective was to
      compare levels of problematic alcohol use (hazardous, harmful or probable
      dependence), gender and age among study participants from clinical psychiatric
      and addiction outpatient settings and from population-based telephone helpline
      users and Internet help-seeker samples. RESULTS: The Alcohol Use Disorders
      Identification Test (AUDIT) was used for screening of problematic alcohol use and
      6-month follow-up assessment. A total of 248 of help-seekers with at least
      hazardous use (AUDIT scores of >= 6/>= 8 for women/men) were recruited from
      clinical and general population settings. Minor recruitment group differences
      were identified with respect to AUDIT scores and age at baseline. One hundred and
      sixty persons (64.5%) did not complete the follow-up assessment. The attrition
      group had a higher proportion of probable dependence (71% vs. 56%; p = 0.025),
      and higher scores on the total AUDIT, and its subscales for alcohol consumption
      and alcohol problems. At follow up, within-group problem levels had declined
      across all three groups, but there were no significant between-group differences.
      Trial registration ClinicalTrials.gov NCT01958359, Registered October 9, 2013.
      Retrospectively registered.

PMID- 29183359
TI  - Acute on chronic bilateral subdural hematoma presenting with acute complete
      flaccid paraplegia and urinary retention mimicking an acute spinal cord injury: a
      case report.
AB  - BACKGROUND: A subdural hematoma refers to a collection of blood between the dura
      and the arachnoid membranes and is classified into acute, sub acute and chronic.
      Subdural hematoma has been referred to as the "great neurologic imitator" as it
      can mimic many neurological conditions. CASE PRESENTATION: Forty-three year old
      Sri Lankan female presented 2 weeks following traumatic head injury with
      bilateral flaccid complete paraplegia and urinary retention. Her non-contrast
      computer tomography of the brain revealed bilateral acute, chronic subdural
      hematomas. Both subdural hematomas were aspirated and she recovered completely.
      CONCLUSIONS: Chronic subdural hematoma can present in many different unusual ways
      including bilateral complete paraplegia and acute urinary retention mimicking
      acute spinal cord pathology. The exact mechanism of this clinical presentation is
      not clear and may be due to direct compression of the motor cortex to the falx or
      due to compression of the anterior cerebral artery due to subfalcine herniation.
      This case illustrates the importance of considering subdural hematoma as a rare
      cause for acute paraplegia and the importance of performing a computer tomography
      scan in traumatic brain injury when indicated. Failure to consider non-spinal
      causes of paraplegia results in potential mismanagement. According to our
      knowledge this is the first case report of acute on chronic subdural hematoma
      presenting as acute flaccid complete paraplegia with urinary retention.

PMID- 29183360
TI  - Misclassification of child body mass index from cut-points defined by rounded
      percentiles instead of Z-scores.
AB  - OBJECTIVE: To evaluate the misclassification resulting from the use of body mass
      index (BMI) cut-points defined by rounded percentiles instead of Z-scores in
      early childhood. Using data from the TARGet Kids primary care network we
      conducted a cross-sectional study among 5836 children < 6 years of age. The World
      Health Organization growth standards were used to calculate BMI-for-age Z-scores.
      BMI Z-score cut-points of < - 2.0, > 1.0, > 2.0, > 3.0 are recommended to define
      wasted, at risk of overweight, overweight and obese. However, rounded percentiles
      of the 3rd, 85th, 97th, and 99.9th are commonly used. Misclassification was
      calculated comparing the frequency distributions for BMI categories defined by
      rounded percentiles and Z-score cut-points. RESULTS: Using rounded percentiles,
      the proportion of children who were wasted, at risk of overweight, overweight,
      and obese was 4.2, 12.5, 4.3 and 0.8%, whereas the distribution using Z-scores
      was: 3.6, 13.8, 3.4 and 1.0%, respectively. Overall, 117 (2%) children were
      misclassified when using percentiles instead of Z-scores; however, 13% (33/245)
      of children who were wasted and 14% (8/57) of children who were obese were
      misclassified. Misclassification of child growth results from the use of cut
      points defined by rounded percentiles instead of Z-scores and limits
      comparability between studies. Trial registration Clinicaltrials.gov NCT01869530
      June 5, 2013.

PMID- 29183361
TI  - Naringenin attenuates hepatitis B virus X protein-induced hepatic steatosis.
AB  - BACKGROUND: Naringenin (Nar), a common dietary flavonoid abundantly present in
      fruits, vegetables, and Chinese herbs, is believed to possess strong anti
      inflammatory properties and to modulate hepatic apolipoprotein and lipid
      synthesis. However, there are no reports describing Nar's effects on the
      hepatitis B virus protein X (HBx) -induced hepatic steatosis, and the detailed
      molecular mechanisms of the compound's effects are still unclear. METHODS: Nar
      was administered by oral gavage to HBx-transgenic mice from 4 to 6 weeks of age.
      Mice were sacrificed after 14 days of once-daily naringenin administration. Liver
      tissues and sera were collected for histopathology and biochemical analysis.
      RESULTS: Nar counteracted hepatic lipid accumulation and liver dysfunction in HBx
      transgenic mice. In addition, Nar significantly decreased expression of
      adipogenic and lipogenic genes in mice, suggesting that the compound may have
      therapeutic effects in the early stages of HBx-mediated hepatic steatosis. These
      results indicated that naringenin inhibits HBx-induced expression of hepatic
      adipogenic and lipogenic genes through suppression of HBx-induced gene
      expression, including decreases in the transcriptional activity of SREBP1c,
      LXRalpha, and PPARgamma in HBx-trangenic mice and HBx-transfected HepG2 cells.
      CONCLUSIONS: Results from this study suggested that Nar may serve as a
      therapeutic agent for preventing HBx-infected hepatic steatosis in humans.

PMID- 29183362
TI  - Unifying the functional diversity in natural and cultivated soils using the
      overall body-mass distribution of nematodes.
AB  - BACKGROUND: Sustainable use of our soils is a key goal for environmental
      protection. As many ecosystem services are supported belowground at different
      trophic levels by nematodes, soil nematodes are expected to provide objective
      metrics for biological quality to integrate physical and chemical soil variables.
      Trait measurements of body mass carried out at the individual level can in this
      way be correlated with environmental properties that influence the performance of
      soil biota. RESULTS: Soil samples were collected across 200 sites (4 soil types
      and 5 land-use types resulting in 9 combinations) during a long-term monitoring
      programme in the Netherlands and the functional diversity of nematode communities
      was investigated. Using three commonly used functional diversity indices
      applicable to single traits (Divergence, Evenness and Richness), a unified index
      of overall body-mass distribution is proposed to better illustrate the
      application of functional metrics as a descriptor of land use. Effects of land
      use and soil chemistry on the functional diversity of nematodes were demonstrated
      and a combination of environmental factors accounts for the low functional value
      of Scots Pine forest soils in comparison to the high functional value of
      heathland soils, whereas human factors account for the low functional and
      chemical values of arable fields. CONCLUSIONS: These findings show an unexpected
      high functional vulnerability of nematodes inhabiting clay-rich soils in
      comparison to sandy soils and support the notion that soil C:N ratio is a major
      driver of biodiversity. The higher the C:N ratio, the higher the overall
      diversity, as soil nematodes cope better with nutrient-poor agroecosystems under
      less intense fertilization. A trait-based way focusing on size distribution of
      nematodes is proposed to maintain environmental health by monitoring the overall
      diversity in soil biota, keeping agriculture and forestry sustainable.

PMID- 29183363
TI  - Motivation and academic performance of medical students from ethnic minorities
      and majority: a comparative study.
AB  - BACKGROUND: Medical students from ethnic minorities underperform in knowledge and
      skills assessments both in pre-clinical and clinical education compared to the
      ethnic majority group. Motivation, which influences learning and academic
      performance of medical students, might play an important role in explaining these
      differences, but is under-investigated. This study aimed to compare two types of
      motivation (autonomous and controlled) of ethnic minority (Western and non
      Western) and majority (Dutch) students, and their association with academic
      performance. METHODS: In a cross-sectional study, all students of a Dutch medical
      school were invited to complete a survey including the Academic Self-Regulation
      Questionnaire, measuring autonomous and controlled motivation, in the academic
      year 2015-2016. Motivation was compared using Kruskal-Wallis test and performance
      was compared using One-Way ANOVA. Linear regression analysis was used to
      determine the association between motivation and performance (grade point
      average; GPA). RESULTS: The response rate was 38.6% (n = 947). Autonomous
      motivation (AM) of non-Western students was higher than that of Dutch students in
      pre-clinical and clinical education (p < 0.05). Controlled motivation was higher
      in Western students than in Dutch students (pre-clinical education; p < 0.05). AM
      was associated with a higher GPA for Dutch (pre-clinical education; beta = 0.33,
      p < 0.05) and Western students (clinical education; beta = 0.57, p < 0.05) only.
      CONCLUSIONS: Our results show significant differences in the type of motivation
      between the ethnic majority and minority groups. The association of motivation
      with performance also differs between ethnic groups. We found that AM has a
      positive influence on GPA. Further research is needed to uncover the underlying
      mechanisms.

PMID- 29183364
TI  - Unusual presentations of functional parathyroid cysts: a case series and review
      of the literature.
AB  - BACKGROUND: Cysts of parathyroid origin are sometimes encountered and can easily
      be mistaken as thyroidal cysts. Functional parathyroid cysts, with symptoms and
      signs of hyperparathyroidism, are rare and may be a diagnostic challenge to
      clinicians. We report here on three cases of functional parathyroid cysts that
      illustrate diagnosis difficulties related to unusual clinical presentations in
      three Caucasian women, including negative parathyroid scintigraphy. CASE
      PRESENTATIONS: Patient 1, an 87-year-old Caucasian woman presented with confusion
      and dysphagia. She had hypercalcemia and elevated parathyroid hormone levels
      suggesting primary hyperparathyroidism. Parathyroid scintigraphy did not reveal
      any focal uptake, but a computed tomography scan of her neck identified a large
      cyst in the upper right thyroid region. At cervicotomy, a parathyroid cystic
      adenoma was removed. Patient 2, a 31-year-old Caucasian woman was investigated
      after a hypertensive crisis related to primary hyperparathyroidism. Cervical
      ultrasound identified a large cystic lesion in the lower left thyroid lobe that
      was removed by minimally invasive cervicotomy. Patient 3, a 34-year-old Caucasian
      woman presented with an indolent growing mass of the neck and a past medical
      history of kidney stones. Primary hyperparathyroidism was diagnosed. Ultrasound
      showed a cystic mass, but parathyroid scintigraphy was negative. Cervical
      exploration revealed a large cystic adenoma, containing high parathyroid hormone
      levels. CONCLUSIONS: Diagnosis of functional parathyroid cysts can be challenging
      due to various clinical presentations and negative parathyroid scintigraphy.
      Surgery, but not fine-needle sclerotherapy, appears to be the safest treatment
      option. Despite its rarity, differential diagnosis of cystic lesion of the neck
      should include primary hyperparathyroidism due to functional parathyroid cysts.

PMID- 29183365
TI  - African and classical swine fever: similarities, differences and epidemiological
      consequences.
AB  - For the global pig industry, classical (CSF) and African swine fever (ASF)
      outbreaks are a constantly feared threat. Except for Sardinia, ASF was eradicated
      in Europe in the late 1990s, which led to a research focus on CSF because this
      disease continued to be present. However, ASF remerged in eastern Europe in 2007
      and the interest in the disease, its control and epidemiology increased
      tremendously. The similar names and the same susceptible species suggest a
      similarity of the two viral diseases, a related biological behaviour and,
      correspondingly, similar epidemiological features. However, there are several
      essential differences between both diseases, which need to be considered for the
      design of control or preventive measures. In the present review, we aimed to
      collate differences and similarities of the two diseases that impact epidemiology
      and thus the necessary control actions. Our objective was to discuss critically,
      if and to which extent the current knowledge can be transferred from one disease
      to the other and where new findings should lead to a critical review of measures
      relating to the prevention, control and surveillance of ASF and CSF. Another
      intention was to identify research gaps, which need to be closed to increase the
      chances of a successful eradication of ASF and therefore for a decrease of the
      economic threat for pig holdings and the international trade.

PMID- 29183366
TI  - The effect on the patient flow in local health care services after closing a
      suburban primary care emergency department: a controlled longitudinal follow-up
      study.
AB  - BACKGROUND: It has not been studied what happens to patient flow to EDs and other
      parts of local health care system if distances to ED services are manipulated as
      a part of health policy in urban areas. METHODS: The present work was an
      observational and quasi-experimental study with a control and it was based on
      before-after comparisons. The impact of terminating a geographically distant
      suburban primary care ED on patient flow to doctors in local public primary care
      EDs, office-hour primary care, secondary care EDs and in private primary care was
      studied. The effect of this intervention was compared with a primary care system
      where no similar intervention was performed. The number of monthly visits to
      doctors in different departments of health care was scored as the main measure of
      the study in each department studied (e.g. in primary care EDs, secondary care
      ED, office-hour public primary care and private primary care). Monthly mortality
      rates were also recorded. RESULTS: Increasing the distance to ED services by
      terminating a peripheral ED did not cause an increase in the use of local office
      hour services in those areas whose local ED was terminated, although use of ED
      services decreased by 25% in these areas (P < 0.001). The total use of primary
      care doctor services rather decreased - if anything - after this intervention
      while use of doctor services in secondary care ED remained unaffected. Doctor
      visits to the complementary private primary care increased but this was probably
      not associated with the intervention because a simultaneous increase in this
      parameter was observed in the control. There was no increased mortality in any
      age groups. CONCLUSION: Manipulating distances to ED services can be used to
      direct patient flows to different parts of the health care system. The
      correlation between distance to ED and the tendency to use ED by inhabitants is
      negative. If secondary care ED was available there were no life-threatening side
      effects at the level of general public health when a minor ED was closed in a
      primary care ED system.

PMID- 29183367
TI  - Prevalence and associated factors of hypertension among adults in Ethiopia: a
      community based cross-sectional study.
AB  - BACKGROUND: Hypertension is a growing public health problem in many developing
      countries including Ethiopia. It is a silent killer and most patients are
      detected to have it incidentally when they are admitted to hospital for unrelated
      disease or subjected to pre-employment or preoperative medical checkups.
      Information on the prevalence of hypertension and its associated factors is to be
      considered vital to focus and improve prevention and control of cardiovascular
      diseases. The study design was a cross-sectional survey. The study population
      consisted of adults aged 25-65 years who lived in Jigjiga city of eastern
      Ethiopia for at least 6 months. Data were collected using a pretested structured
      questionnaire, and blood pressure was measured using standardized instruments by
      trained clinical nurses. Hypertension was defined as having Systolic BP >= 140
      mmHg or Diastolic BP >= 90 mmHg or reported use of regular anti-hypertensive
      medications prescribed by professionals for raised BP. Data were entered into a
      computer using Epi Info Version 3.5.1 and exported to SPSS version 16.0 for
      analysis. Multiple logistic regressions were fitted and Odds ratios with 95%
      confidence intervals were calculated to identify independently associated
      factors. RESULTS: The prevalence of hypertension was 28.3%. Family history of
      Hypertension [Adjusted OR 5.7; 95% CI (2.9, 10.9)], having high level of income
      [Adjusted OR 3.1; 95% CI (1.5, 6.3)], being male [Adjusted OR 2.4; 95% CI (1.3,
      4.3)], being above grade 12 [Adjusted OR 2.2; 95% CI (1.2, 3.9)], and having BMI
      >= 25 [Adjusted OR 2.0; 95% CI (1.1, 3.5)] were significantly associated with
      hypertension. CONCLUSION: Consistent with the literatures, the prevalence of
      hypertension was high and may show a hidden epidemic in this population. If
      established with more robust and nationally representative studies, the finding
      calls for efficient health screening and regular checkups as well as
      interventions promoting healthy lifestyles. Accordingly, health promotion
      regarding hypertension should be provided in the population as means of primary
      prevention.

PMID- 29183368
TI  - Incidence of orthostatic hypotension and cardiovascular response to postoperative
      early mobilization in patients undergoing cardiothoracic and abdominal surgery.
AB  - BACKGROUND: In cardiothoracic and abdominal surgery, postoperative complications
      remain major clinical problems. Early mobilization has been widely practiced and
      is an important component in preventing complications, including orthostatic
      hypotension (OH) during postoperative management. We investigated cardiovascular
      response during early mobilization and the incidence of OH after cardiothoracic
      and abdominal surgery. METHODS: In this prospective observational study, we
      consecutively analyzed data from 495 patients who underwent elective
      cardiothoracic and abdominal surgery. We examined the incidence of OH, and the
      independent risk factors associated with OH during early mobilization after major
      surgery. Multivariate logistic regression was performed using various
      characteristics of patients to identify OH-related independent factors. RESULTS:
      OH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac,
      thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%)
      of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural
      anesthesia (OR 2.906; p < 0.001) were independently associated with OH on
      multivariate analysis. CONCLUSIONS: These results demonstrate that approximately
      40% patients experience OH during early mobilization after cardiothoracic and
      abdominal surgery. Sex was identified as an independent factor for OH during
      early mobilization after all three types of surgeries, while epidural anesthesia
      was only identified after thoracic surgery. Therefore, the frequent occurrence of
      OH during postoperative early mobilization should be recognized. TRIAL
      REGISTRATION: University hospital Medical Information Network Center (UMIN-CTR)
      number UMIN000018632 . (Registered on 1st October, 2008).

PMID- 29183369
TI  - Improving tuberculosis case detection in underdeveloped multi-ethnic regions with
      high disease burden: a case study of integrated control program in China.
AB  - BACKGROUND: In the underdeveloped multi-ethnic regions of China, high
      tuberculosis (TB) burden and regional inequity in access to healthcare service
      increase the challenge of achieving the End TB goals. Among all the provinces,
      the highest TB burden is reported in Xinjiang, where ethnic minorities and older
      people have suffered most. However, current case-finding strategy is inadequate
      given the complex social determinants and suboptimal case detection rates. Thus,
      we developed an integrated TB control program to improve case detection and
      conducted a pilot in Xinjiang from 2014 to 2015. In this case study, we
      summarized the activities and key findings. We also shared the experiences and
      challenges of implementing interventions and provided recommendations to inform
      the TB control program in the future. CASE PRESENTATION: The pilot interventions
      were implemented in one selected town in Yining based on local TB control
      programs. By applying tailor-made educational materials, outreach TB educational
      activities were conducted in diverse ways. In 22 Masjids, the trained imams
      promoted TB education to the Muslims, covering 20,440 person-times in 88
      delivered preaching sessions. In seven schools, 1944 students were educated by
      the teachers and contributed to educating 6929 family members. In the village
      communities, 13,073 residents participated in household education and screening.
      Among them, 12,292 people aged under 65 years were investigated for suspicious
      pulmonary TB symptoms, where six TB patients were diagnosed out of 89 TB
      suspects; 781 older people were mobilized for screening directly by chest X-ray,
      where 10 patients were diagnosed out of 692 participants. Supportive healthcare
      system, multi-sectoral cooperation and multi-channel financing mechanism were the
      successful experiences of implementation. The interventions were proved to be
      more effective than the previous performance: the number of TB suspects
      consulting doctors and patients detected increased by 50% and 26%, respectively.
      The potential challenges, implications and recommendations should been taken into
      account for further program improvement. CONCLUSIONS: In underdeveloped multi
      ethnic regions with high TB burden, improving case detection is necessary and the
      interventions can be feasible and effective within a supportive system. More
      intensive educational and training approaches, a high index of TB suspicion and
      prioritization of older people in screening are recommended. To sustain and scale
      up the program, the impacts, cost-effectiveness, feasibility and acceptability of
      interventions warrant further research and evaluation in each specific context.

PMID- 29183370
TI  - Towards malaria elimination in Savannakhet, Lao PDR: mathematical modelling
      driven strategy design.
AB  - BACKGROUND: The number of Plasmodium falciparum malaria cases around the world
      has decreased substantially over the last 15 years, but with the spread of
      resistance against anti-malarial drugs and insecticides, this decline may not
      continue. There is an urgent need to consider alternative, accelerated strategies
      to eliminate malaria in countries like Lao PDR, where there are a few remaining
      endemic areas. A deterministic compartmental modelling tool was used to develop
      an integrated strategy for P. falciparum elimination in the Savannakhet province
      of Lao PDR. The model was designed to include key aspects of malaria transmission
      and integrated control measures, along with a user-friendly interface. RESULTS:
      Universal coverage was the foundation of the integrated strategy, which took the
      form of the deployment of community health workers who provided universal access
      to early diagnosis, treatment and long-lasting insecticidal nets. Acceleration
      was included as the deployment of three monthly rounds of mass drug
      administration targeted towards high prevalence villages, with the addition of
      three monthly doses of the RTS,S vaccine delivered en masse to the same high
      prevalence sub-population. A booster dose of vaccine was added 1 year later. The
      surveillance-as-intervention component of the package involved the screening and
      treatment of individuals entering the simulated population. CONCLUSIONS: In this
      modelling approach, the sequential introduction of a series of five available
      interventions in an integrated strategy was predicted to be sufficient to stop
      malaria transmission within a 3-year period. These interventions comprised
      universal access to early diagnosis and adequate treatment, improved access to
      long-lasting insecticidal nets, three monthly rounds of mass drug administration
      together with RTS,S vaccination followed by a booster dose of vaccine, and
      screening and treatment of imported cases.

PMID- 29183371
TI  - Cytotoxic activity of NN-32 toxin from Indian spectacled cobra venom on human
      breast cancer cell lines.
AB  - BACKGROUND: Breast cancer is the most common cancer which causes significant
      morbidity and mortality among women worldwide. Lack of medical facilities for
      early detection, therapeutic strategies for treatment and side effects due to
      pharmacological compounds have encompassed the need for new therapies mostly from
      natural sources. A lot of components have been identified from different snake
      venoms as therapeutic agents. A group of polypeptides (60-70 amino acid residues)
      called cytotoxins or cardiotoxins present in an elapid family of snakes have a
      wide variety of pharmaceutical actions and have the tendency to damage a wide
      variety of cells including cancerous cells. The aim of the present study was to
      evaluate the cytotoxic effect of NN-32 protein toxin purified from Indian
      Spectacled Cobra venom against human breast cancer cell lines (MCF-7 and MDA-MB
      231). METHODS: The NN-32 toxin was purified by ion exchange chromatography and
      further by RP-HPLC. The potential anticancer effects of the NN-32 toxin on MCF-7
      and MDA-MB-231 cells were evaluated using MTT, anti-proliferation, neutral red
      (NR) uptake and Lactate Dehydrogenase (LDH) release assay. RESULTS: The ion
      exchange chromatography showed various peaks among fraction no. 35 showing
      cytotoxic activity and this fraction showed a single peak with retention time 3.6
      mins by HPLC using C18 column. The NN-32 toxin induced cytotoxicity in MCF-7 and
      MDA-MB-231 cells with the IC50 value of 2.5 and 6.7 MUg/ml respectively. The NN
      32 showed significant cytotoxicity to both the cell lines along with low
      cytotoxicity to MCF-10A (normal breast epithelial) cells. The cytotoxic effect
      was further confirmed by the anti-proliferative, NR uptake and LDH release
      assays. CONCLUSION: The purified toxin NN-32 from Naja naja venom showed
      cytotoxic activity against MCF-7 (ER+) and MDA-MB-231(ER-) cells in both dose
      dependent and time dependent manner.

PMID- 29183372
TI  - Patient preferences for direct-to-consumer telemedicine services: a nationwide
      survey.
AB  - BACKGROUND: Direct-to-consumer (DTC) telemedicine providers has the potential to
      change the traditional patient-physician relationship. Professional medical
      organizations recommend that telemedicine exist within the medical home. This
      study aims to understand patients' preferences and desires for DTC telemedicine.
      METHODS: We conducted a nationwide survey of 4345 survey respondents
      demographically balanced to represent the United States adult population. The
      survey consisted of questions assessing the respondents' attributes and their
      willingness and comfortability using telemedicine as well as the importance and
      desired attributes of a provider providing care via telemedicine. RESULTS:
      Relatively few respondents (3.5%) had ever had an online video visit with their
      care provider. Respondents were more willing to see their own provider via
      telemedicine than unwilling (52% vs. 25%). Additionally, respondents were less
      willing to use telemedicine to see a different provider from the same healthcare
      organization (35%) and were least willing to see a different provider from a
      different organization (19%). Forty-one percent of respondents felt it was
      unimportant that their current provider offer telemedicine, and only 15% would
      consider leaving their current provider to a new provider who offers telemedicine
      as an option. More than half (56%) of respondents felt it was important to have
      an established relationship with a provider they're having a telemedicine visit
      with. Nearly two-thirds of respondents (60%) felt it was important for a
      telemedicine provider to have access to their health records. CONCLUSIONS:
      Patients prefer to use telemedicine with their own doctor with whom they have an
      established relationship.

PMID- 29183373
TI  - Back pain in physically inactive students compared to physical education students
      with a high and average level of physical activity studying in Poland.
AB  - BACKGROUND: The aim of the study was (1) to characterise back pain in physically
      inactive students as well as in trained (with a high level of physical activity)
      and untrained (with an average level of physical activity) physical education
      (PE) students and (2) to find out whether there exist differences regarding the
      declared incidence of back pain (within the last 12 months) between physically
      inactive students and PE students as well as between trained (with a high level
      of physical activity) and untrained (with an average level of physical activity)
      PE students. METHODS: The study included 1321 1st-, 2nd- and 3rd-year students
      (full-time bachelor degree course) of Physical Education, Physiotherapy, Pedagogy
      as well as Tourism and Recreation from 4 universities in Poland. A questionnaire
      prepared by the authors was applied as a research tool. The 10-point Visual
      Analogue Scale (VAS) was used to assess pain intensity. Prior to the study, the
      reliability of the questionnaire was assessed by conducting it on the group of 20
      participants twice with a shorter interval. No significant differences between
      the results obtained in the two surveys were revealed (p < 0.05). RESULTS: In the
      group of 1311 study participants, 927 (70.7%) respondents declared having
      experienced back pain within the last 12 months. Physically inactive students
      declared back pain frequency similar to the frequency declared by their
      counterparts studying physical education (p > 0.05). Back pain was more common in
      the group of trained students than among untrained individuals (p < 0.05). Back
      pain was mainly located in the lumbar spine. CONCLUSIONS: A frequent occurrence
      of back pain (70.7%) was noted in the examined groups of students. The percentage
      of students declaring back pain increased in the course of studies (p < 0.05)
      and, according to the students' declarations, it was located mainly in the lumbar
      spine. No significant differences regarding the incidence of back pain were found
      between physically inactive students and physical education students (p > 0.05).
      The trained students declared back pain more often than their untrained
      counterparts (p < 0.05).

PMID- 29183374
TI  - Optimizing recombinant protein expression via automated induction profiling in
      microtiter plates at different temperatures.
AB  - BACKGROUND: Escherichia coli (E. coli) is the most abundant expression host for
      recombinant proteins. The production efficiency is dependent on a multitude of
      parameters. Therefore, high-throughput applications have become an increasingly
      frequent technique to investigate the main factors. Within this study, the
      effects of temperature, induction time and inducer concentration on the metabolic
      state and the product formation were extensively examined. Induction profiling of
      E. coli Tuner(DE3) pRhotHi-2-EcFbFP was performed in 48-well Flowerplates and
      standard 96-well plates using a robotic platform. In parallel shake flask
      cultivations, the respiration activity of the microorganisms was analyzed.
      Therefore, two online-monitoring systems were applied: the BioLector for
      microtiter plates and the RAMOS-device for shake flasks. The impact of different
      induction conditions on biomass and product formation as well as on the oxygen
      transfer rate was surveyed. RESULTS: Different optimal induction conditions were
      obtained for temperatures of 28, 30, 34, and 37  degrees C. The best inducer
      concentrations were determined to be between 0.05 and 0.1 mM IPTG for all
      investigated temperatures. This is 10-20 times lower than conventional guidelines
      suggest. The induction time was less relevant when the correct inducer
      concentration was chosen. Furthermore, there was a stronger impact on growth and
      respiration activity at higher temperatures. This indicated a higher metabolic
      burden. Therefore, lower IPTG concentrations were advantageous at elevated
      temperatures. Very similar results were obtained in standard 96-well plates.
      CONCLUSION: Two online-monitoring systems were successfully used to investigate
      the optimal induction conditions for the E. coli Tuner(DE3) pRhotHi-2-EcFbFP
      strain (lacY deletion mutant) at four different temperatures. The experimental
      effort was reduced to a minimum by integrating a liquid handling robot. To reach
      the maximum product formation, a detailed induction analysis was necessary.
      Whenever the cultivation temperature was changed, the induction conditions have
      to be adapted. Due to the experimental options provided by the BioLector
      technology, it was found that the higher the cultivation temperature, the lower
      the inducer concentration that has to be applied.

PMID- 29183375
TI  - RDL mutations predict multiple insecticide resistance in Anopheles sinensis in
      Guangxi, China.
AB  - BACKGROUND: Anopheles sinensis is a major vector of malaria in China. The gamma
      aminobutyric acid (GABA)-gated chloride channel, encoded by the RDL (Resistant to
      dieldrin) gene, is the important target for insecticides of widely varied
      structures. The use of various insecticides in agriculture and vector control has
      inevitably led to the development of insecticide resistance, which may reduce the
      control effectiveness. Therefore, it is important to investigate the presence and
      distribution frequency of the resistance related mutation(s) in An. sinensis RDL
      to predict resistance to both the withdrawn cyclodienes (e.g. dieldrin) and
      currently used insecticides, such as fipronil. METHODS: Two hundred and forty
      adults of An. sinensis collected from nine locations across Guangxi Zhuang
      Autonomous Region were used. Two fragments of An. sinensis RDL (AsRDL) gene,
      covering the putative insecticide resistance related sites, were sequenced
      respectively. The haplotypes of each individual were reconstructed by the
      PHASE2.1 software, and confirmed by clone sequencing. The phylogenetic tree was
      built using maximum-likelihood and Bayesian inference methods. Genealogical
      relations among different haplotypes were also analysed using Network 5.0.
      RESULTS: The coding region of AsRDL gene was 1674 bp long, encoding a protein of
      557 amino acids. AsRDL had 98.0% amino acid identity to that from Anopheles
      funestus, and shared common structural features of Cys-loop ligand-gated ion
      channels. Three resistance-related amino acid substitutions (A296S, V327I and
      T345S) were detected in all the nine populations of An. sinensis in Guangxi, with
      the 296S mutation being the most abundant (77-100%), followed by 345S (22-47%)
      and 327I (8-60%). 38 AsRDL haplotypes were identified from 240 individuals at
      frequencies ranging from 0.2 to 34.8%. Genealogical analysis suggested multiple
      origins of the 345S mutation in AsRDL. CONCLUSIONS: The near fixation of the 296S
      mutation and the occurrence of the 327I and 345S mutations in addition to 296S,
      in all the nine tested An. sinensis populations in Guangxi, strongly indicate a
      risk of multiple insecticide resistance. The haplotype diversity plus genetic
      heterogeneities in the geographical distribution, and multiple origins of AsRDL
      alleles call for a location-customized strategy for monitoring and management of
      insecticide resistance.

PMID- 29183376
TI  - The danger of non-exhaustive quality measures: requiring hip fracture repair
      surgery within 48 hours - a case study.
AB  - Quality measures are widely used globally in order to measure clinical
      performance and organizational efficiency of the healthcare systems. However, in
      a race to achieve certain numerically defined goal, the more important purpose of
      any organizational step being aimed at improving clinical outcomes could be
      overshadowed.The introduction of the requirement to perform most hip fracture
      surgeries in the first 48 h of hospitalization by the Israeli Ministry of Health
      (IMOH) provides an interesting example of the complexity of this phenomenon. In
      2004, the IMOH decided that hospitals would receive the full DRG payment for hip
      fractures operations only in cases in which the operation is performed within 48
      h of hospitalization. In 2013, the IMOH proceeded to designate the proportion of
      less than 48 h surgeries as an official quality parameter for comparing hospital
      performance.Despite the widely acknowledged and proven clinical benefit of
      earlier surgery for hip fracture patients, the desired proportion of such
      surgeries in a given population is not easily defined for a given population, as
      a significant number of patients may be unsuited for immediate surgery due to
      medical instability, having a serious co-morbidity or receiving anticoagulant
      treatment. Rushing these patients to surgery can be therefore expected to have a
      negative effect on their outcomes, and the subsequent increase in hip fracture
      mortality recorded in Israel after 2013 may be a result of that.This example
      suggests that designating an organizational quality measure without adjusting it
      for the patient's medical condition may make it too inaccurate to guide
      healthcare policy.

PMID- 29183377
TI  - Impact of robust treatment planning on single- and multi-field optimized plans
      for proton beam therapy of unilateral head and neck target volumes.
AB  - BACKGROUND: Proton beam therapy is promising for the treatment of head and neck
      cancer (HNC), but it is sensitive to uncertainties in patient positioning and
      particle range. Studies have shown that the planning target volume (PTV) concept
      may not be sufficient to ensure robustness of the target coverage. A few planning
      studies have considered irradiation of unilateral HNC targets with protons, but
      they have only taken into account the dose on the nominal plan, without
      considering anatomy changes occurring during the treatment course. METHODS: Four
      pencil beam scanning (PBS) proton therapy plans were calculated for 8 HNC
      patients with unilateral target volumes: single-field (SFO) and multi-field
      optimized (MFO) plans, either using the PTV concept or clinical target volume
      (CTV)-based robust optimization. The dose was recalculated on computed tomography
      (CT) scans acquired during the treatment course. Doses to target volumes and
      organs at risk (OARs) were compared for the nominal plans, cumulative doses
      considering anatomical changes, and additional setup and range errors in each
      fraction. If required, the treatment plan was adapted, and the dose was compared
      with the non-adapted plan. RESULTS: All nominal plans fulfilled the clinical
      specifications for target coverage, but significantly higher doses on the
      ipsilateral parotid gland were found for both SFO approaches. MFO PTV-based plans
      had the lowest robustness against range and setup errors. During the treatment
      course, the influence of the anatomical variation on the dose has shown to be
      patient specific, mostly independent of the chosen planning approach. Nine plans
      in four patients required adaptation, which led to a significant improvement of
      the target coverage and a slight reduction in the OAR dose in comparison to the
      cumulative dose without adaptation. CONCLUSIONS: The use of robust MFO
      optimization is recommended for ensuring plan robustness and reduced doses in the
      ipsilateral parotid gland. Anatomical changes occurring during the treatment
      course might degrade the target coverage and increase the dose in the OARs,
      independent of the chosen planning approach. For some patients, a plan adaptation
      may be required.

PMID- 29183378
TI  - Vascular abnormalities and development of hypoxia in microscopic melanoma
      xenografts.
AB  - BACKGROUND: Studies investigating the oxygenation status and the development of
      hypoxia in microscopic tumors are sparse. The purpose of this study was to
      measure the extent of hypoxia in microscopic melanoma xenografts and to search
      for possible mechanisms leading to the development of hypoxia in these tumors.
      METHODS: A-07, D-12, R-18, and U-25 human melanoma xenografts grown in dorsal
      window chambers or as flank tumors were used as preclinical tumor models.
      Morphologic and functional parameters of vascular networks were assessed with
      intravital microscopy, and the expression of angiogenesis-related genes was
      assessed with quantitative PCR. Microvessels, pericytes, and the extent of
      hypoxia were assessed by immunohistochemistry in microscopic tumors by using
      CD31, alphaSMA, and pimonidazole as markers, and the extent of radiobiological
      hypoxia was assessed in macroscopic flank tumors. RESULTS: Macroscopic R-18 and U
      25 tumors showed extensive hypoxia, whereas macroscopic A-07 and D-12 tumors were
      less hypoxic. R-18 and U-25 tumors developed hypoxic regions before they reached
      a size of 2-3 mm in diameter, whereas A-07 and D-12 tumors of similar size did
      not show hypoxic regions. The development of hypoxic regions was not caused by
      low vessel density, but was rather a result of inadequate vascular function.
      Inadequate vascular function was not caused by low vessel diameters or long
      vessel segments, but was associated with poor vascular pericyte coverage. Poor
      pericyte coverage was associated with the expression of eight angiogenesis
      related genes. CONCLUSIONS: Two of the four investigated melanoma models
      developed hypoxic regions in microscopic tumors, and the development of hypoxia
      was associated with poor vascular pericyte coverage and inadequate vascular
      function.

PMID- 29183379
TI  - Gait performance and foot pressure distribution during wearable robot-assisted
      gait in elderly adults.
AB  - BACKGROUND: A robotic exoskeleton device is an intelligent system designed to
      improve gait performance and quality of life for the wearer. Robotic technology
      has developed rapidly in recent years, and several robot-assisted gait devices
      were developed to enhance gait function and activities of daily living in elderly
      adults and patients with gait disorders. In this study, we investigated the
      effects of the Gait-enhancing Mechatronic System (GEMS), a new wearable robotic
      hip-assist device developed by Samsung Electronics Co, Ltd., Korea, on gait
      performance and foot pressure distribution in elderly adults. METHODS: Thirty
      elderly adults who had no neurological or musculoskeletal abnormalities affecting
      gait participated in this study. A three-dimensional (3D) motion capture system,
      surface electromyography and the F-Scan system were used to collect data on
      spatiotemporal gait parameters, muscle activity and foot pressure distribution
      under three conditions: free gait without robot assistance (FG), robot-assisted
      gait with zero torque (RAG-Z) and robot-assisted gait (RAG). RESULTS: We found
      increased gait speed, cadence, stride length and single support time in the RAG
      condition. Reduced rectus femoris and medial gastrocnemius muscle activity
      throughout the terminal stance phase and reduced effort of the medial
      gastrocnemius muscle throughout the pre-swing phase were also observed in the RAG
      condition. In addition, walking with the assistance of GEMS resulted in a
      significant increase in foot pressure distribution, specifically in maximum force
      and peak pressure of the total foot, medial masks, anterior masks and posterior
      masks. CONCLUSION: The results of the present study reveal that GEMS may present
      an alternative way of restoring age-related changes in gait such as gait
      instability with muscle weakness, reduced step force and lower foot pressure in
      elderly adults. In addition, GEMS improved gait performance by improving push-off
      power and walking speed and reducing muscle activity in the lower extremities.
      TRIAL REGISTRATION: NCT02843828 .

PMID- 29183380
TI  - Bacterial magnetosomes as an efficient gene delivery platform for cancer
      theranostics.
AB  - BACKGROUND: Gene therapy has gained an increasing interest in its anti-tumor
      efficiency. However, numerous efforts are required to promote them to clinics. In
      this study, a novel and efficient delivery platform based on bacterial
      magnetosomes (BMs) were developed, and the efficiency of BMs in delivering small
      interfering ribonucleic acid (siRNA) as well as antiproliferative effects in
      vitro were investigated. RESULTS: Initially, we optimized the nitrogen/phosphate
      ratio and the BMs/siRNA mass ratio as 20 and 1:2, respectively, to prepare the
      BMs-PEI-siRNA composites. Furthermore, the prepared nanoconjugates were
      systematically characterized. The dynamic light scattering measurements indicated
      that the particle size and the zeta potential of BMs-PEI-siRNA are 196.5 nm and
      49.5 +/- 3.77 mV, respectively, which are optimum for cell internalization.
      Moreover, the confocal laser scanning microscope observations showed that these
      composites were at a proximity to the nucleus and led to an effective silencing
      effect. BMs-PEI-siRNA composites efficiently inhibited the growth of HeLa cells
      in a dose-as well as time-dependent manner. Eventually, a dual stain assay using
      acridine orange/ethidium bromide, revealed that these nanocomposites induced late
      apoptosis in cancer cells. CONCLUSIONS: A novel and efficient gene delivery
      system based on BMs was successfully produced for cancer therapy, and these
      innovative carriers will potentially find widespread applications in the
      pharmaceutical field.

PMID- 29183381
TI  - A promising approach to enhance microalgae productivity by exogenous supply of
      vitamins.
AB  - In order to reduce the consumption of traditional fossil fuels and their impact
      on the environment, strategies to mitigate greenhouse gas emissions especially
      carbon dioxide needs exploration. Microalgae-based biofuels can be the best-fit
      plant based feed-stocks for diminishing a majority of the Universe's energy
      problems. Interestingly, the eukaryotic microalgae aid in fixation of almost 50%
      of the global carbon in the environment. Thus, determination of parameters that
      will enhance microalgal growth and productivity is crucial, if they are to be
      used as future renewable energy sources. A large percentage of phytoplankton
      species are auxotroph for one or more vitamins. These species, in turn, are also
      dependent upon the vitamin biosynthetic pathways for processing of these
      vitamins. The present study serves as a base to discuss the prevalence of vitamin
      auxotrophy in microalgae and the methods of its acquirement from external sources
      such as heterotrophic bacteria. The next section of the paper sheds light on
      possible species-specific symbiotic interactions among microalgae and bacteria.
      Lastly is the discussion on how heterotrophic bacteria can act as a vitamin
      prototroph for an explicit microalgal vitamin auxotroph. The overall focus is
      placed upon harnessing these symbiotic interactions with intentions to obtain
      enhancements in microalgal biomass, lipid productivity, and flocculation rates.
      Moreover, the growth and distribution of a microalgal cell that thrives on a
      specific vitamin is perhaps met by growing it with the bacterial communities that
      nourish it. Thus, possibly by ecologically engineering a potential species
      specific microalgal-bacterial consortium, it could tremendously contribute to the
      acceleration of photosynthetic activity, microalgal productivity, exchange of
      primary metabolites and other biogeochemical nutrients within the mini ecosystem.

PMID- 29183382
TI  - A proposal for the withdrawal of inhaled corticosteroids in the clinical practice
      of chronic obstructive pulmonary disease.
AB  - According to the current clinical practice guidelines for chronic obstructive
      pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long
      acting beta2 agonist therapy is recommended in patients with moderate-to-severe
      disease and an increased risk of exacerbations. However, ICS are largely
      overprescribed in clinical practice, and most patients are unlikely to benefit
      from long-term ICS therapy.Evidence from recent randomized-controlled trials
      supports the hypothesis that ICS can be safely and effectively discontinued in
      patients with stable COPD and in whom ICS therapy may not be indicated, without
      detrimental effects on lung function, health status, or risk of exacerbations.
      This article summarizes the evidence supporting the discontinuation of ICS
      therapy, and proposes an algorithm for the implementation of ICS withdrawal in
      patients with COPD in clinical practice.Given the increased risk of potentially
      serious adverse effects and complications with ICS therapy (including pneumonia),
      the use of ICS should be limited to the minority of patients in whom the
      treatment effects outweigh the risks.

PMID- 29183383
TI  - The opioid epidemic: a central role for the blood brain barrier in opioid
      analgesia and abuse.
AB  - Opioids are currently the primary treatment method used to manage both acute and
      chronic pain. In the past two to three decades, there has been a surge in the
      use, abuse and misuse of opioids. The mechanism by which opioids relieve pain and
      induce euphoria is dependent on the drug crossing the blood-brain barrier and
      accessing the central nervous system. This suggests the blood brain barrier plays
      a central role in both the benefits and risks of opioid use. The complex
      physiological responses to opioids that provide the benefits and drive the abuse
      also needs to be considered in the resolution of the opioid epidemic.

PMID- 29183384
TI  - Core Health Outcomes In Childhood Epilepsy (CHOICE): protocol for the selection
      of a core outcome set.
AB  - BACKGROUND: There is increasing recognition that establishing a core set of
      outcomes to be evaluated and reported in trials of interventions for particular
      conditions will improve the usefulness of health research. There is no
      established core outcome set for childhood epilepsy. The aim of this work is to
      select a core outcome set to be used in evaluative research of interventions for
      children with rolandic epilepsy, as an exemplar of common childhood epilepsy
      syndromes. METHODS: First we will identify what outcomes should be measured; then
      we will decide how to measure those outcomes. We will engage relevant UK
      charities and health professional societies as partners, and convene advisory
      panels for young people with epilepsy and parents of children with epilepsy. We
      will identify candidate outcomes from a search for trials of interventions for
      childhood epilepsy, statutory guidance and consultation with our advisory panels.
      Families, charities and health, education and neuropsychology professionals will
      be invited to participate in a Delphi survey following recommended practices in
      the development of core outcome sets. Participants will be able to recommend
      additional outcome domains. Over three rounds of Delphi survey participants will
      rate the importance of candidate outcome domains and state the rationale for
      their decisions. Over the three rounds we will seek consensus across and between
      families and health professionals on the more important outcomes. A face-to-face
      meeting will be convened to ratify the core outcome set. We will then review and
      recommend ways to measure the shortlisted outcomes using clinical assessment
      and/or patient-reported outcome measures. DISCUSSION: Our methodology is a
      proportionate and pragmatic approach to expediently produce a core outcome set
      for evaluative research of interventions aiming to improve the health of children
      with epilepsy. A number of decisions have to be made when designing a study to
      develop a core outcome set including defining the scope, choosing which
      stakeholders to engage, most effective ways to elicit their views, especially
      children and a potential role for qualitative research.

PMID- 29183385
TI  - An investigation into aflatoxin M 1 in slaughtered fattening pigs and awareness
      of aflatoxins in Vietnam.
AB  - BACKGROUND: Aflatoxin M1 (AFM1) is a hydroxylated metabolite formed after
      aflatoxin B1 (AFB1) is consumed by humans and animals; it can be detected in
      urine, milk and blood. It is well recognized that AFB1 is toxic to humans and
      other animals. The International Agency for Research on Cancer (IARC) classifies
      aflatoxins as group 1 carcinogens and AFM1 as group 2B carcinogen. The main
      objective of this study was to evaluate the exposure of pigs to aflatoxins as
      well as to assess the public awareness of aflatoxins among people in five
      provinces in Vietnam. RESULTS: A total of 1920 urine samples were collected from
      slaughterhouses located in five provinces. Overall, the positive rate of AFM1 was
      53.90% (95% confidence interval 51.64-56.15) using a cut-off of 0.15 MUg/kg
      (range: limit of detection to 13.66 MUg/kg, median: 0.2 MUg/kg and mean: 0.63
      MUg/kg). A total of 252 people from the general population were interviewed from
      5 provinces, and overall 67.86% reported being aware of aflatoxins. We also found
      that men and more highly educated had significantly increased awareness of
      aflatoxins compared to the females and primary/secondary school group. The
      respective odds ratios (ORs) were as follows: "male" group (OR: 2.64), "high
      school educated" group (OR: 3.40) and "college/university or more educated" group
      (OR: 10.20). CONCLUSIONS: We can conclude that pigs in Vietnam are exposed to
      aflatoxins to varying degrees, and there may be a risk that pork products could
      contain AFM1. Further investigation is needed into the possible health impacts as
      well as to aid in establishing regulations for animal feed to reduce the health
      impacts in humans and animals.

PMID- 29183386
TI  - Application of survival tree analysis for exploration of potential interactions
      between predictors of incident chronic kidney disease: a 15-year follow-up study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a growing public health challenges
      worldwide. Various studies have investigated risk factors of incident CKD;
      however, a very few studies examined interaction between these risk factors. In
      an attempt to clarify the potential interactions between risk factors of CKD, we
      performed survival tree analysis. METHODS: A total of 8238 participants (46.1%
      men) aged > 20 years without CKD at baseline [(1999-2001) and (2002-2005)], were
      followed until 2014. The first occurrence of CKD, defined as the estimated
      glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, was set as the main
      outcome. Multivariable Cox proportional hazard (Cox PH) regression was used to
      identify significant independent predictors of CKD; moreover, survival tree
      analysis was performed to gain further insight into the potential interactions
      between predictors. RESULTS: The crude incidence rates of CKD were 20.2 and 35.2
      per 1000 person-years in men and women, respectively. The Cox PH identified the
      main effect of significant predictors of CKD incidence in men and women. In
      addition, using a limited number of predictors, survival trees identified 12 and
      10 subgroups among men and women, respectively, with different survival
      probability. Accordingly, a group of men with eGFR > 74 ml/min/1.73 m2, age <= 46
      years, low level of physical activity, waist circumference <= 100 cm and FPG <=
      4.7 mmol/l had the lowest risk of CKD incidence; while men with eGFR <= 63.4
      ml/min/1.73 m2, age > 50 years had the highest risk for CKD compared to men in
      the lowest risk group [hazard ratio (HR), 70.68 (34.57-144.52)]. Also, a group of
      women aged <= 45 years and eGFR > 83.5 ml/min/1.73 m2 had the lowest risk; while
      women with age > 48 years and eGFR <= 69 ml/min/1.73 m2 had the highest risk
      compared to low risk group [HR 27.25 (19.88-37.34)]. CONCLUSION: In this post hoc
      analysis, we found the independent predictors of CKD using Cox PH; furthermore,
      by applying survival tree analysis we identified several numbers of homogeneous
      subgroups with different risk for incidence of CKD. Our study suggests that two
      methods can be used simultaneously to provide new insights for intervention
      programs and improve clinical decision making.

PMID- 29183387
TI  - Nanopore sequencing of full-length BRCA1 mRNA transcripts reveals co-occurrence
      of known exon skipping events.
AB  - BACKGROUND: Laboratory assays evaluating the effect of DNA sequence variants on
      BRCA1 mRNA splicing may contribute to classification by providing molecular
      evidence. However, our knowledge of normal and aberrant BRCA1 splicing events to
      date has been limited to data derived from assays targeting partial transcript
      sequences. This study explored the utility of nanopore sequencing to examine
      whole BRCA1 mRNA transcripts and to provide accurate categorisation of in-frame
      and out-of-frame splicing events. METHODS: The exon structure of BRCA1
      transcripts from a previously studied control lymphoblastoid cell line were
      assessed using MinION nanopore sequencing of long-range reverse transcriptase-PCR
      amplicons. RESULTS: Our study identified and characterised 32 complete BRCA1
      isoforms, including 18 novel isoforms which showed skipping of multiple
      contiguous and/or non-contiguous exons. Furthermore, we show that known BRCA1
      exon skipping events, such as Delta(9,10) and Delta21, can co-occur in a single
      transcript, with some isoforms containing four or more alternative splice
      junctions. Fourteen novel isoforms were formed entirely from a combination of
      previously identified alternative splice junctions, suggesting that the total
      number of BRCA1 isoforms might be lower than the number of splicing events
      reported previously. CONCLUSIONS: Our results highlight complexity in BRCA1
      transcript structure that has not been described previously. This finding has key
      implications for predicting the translation frame of splicing transcripts,
      important for interpreting the clinical significance of spliceogenic variants.
      Future research is warranted to quantitatively assess full-length BRCA1
      transcript levels, and to assess the application of nanopore sequencing for
      routine evaluation of potential spliceogenic variants.

PMID- 29183388
TI  - Restraint use among selected hospitalized elderly patients in Cairo, Egypt.
AB  - OBJECTIVE: This study's primary objective was to investigate the prevalence of
      physical and chemical restraint use in selected elderly hospitalized patients.
      RESULTS: This study was conducted in April 2014 in four major acute care
      hospitals. Trained data collectors assessed the use of physical and chemical
      restraint among all admitted elderly patients. There were 287 elderly patients
      (median age 64 years, 46% women). 32 patients were restrained. The overall
      prevalence of restraints was 11.1%, with physical restraint use alone at 3.2% and
      chemical restraints use alone at 7.3%. Restraint use varied by hospital type,
      with the highest at the private hospital (22.9%) and the lowest at the two
      university hospitals (< 6%). In conclusion the prevalence of physical and
      chemical restraint use among admitted elderly patients in Egypt is comparable to
      that seen in developed countries. However, the use appears to vary widely by
      hospital type. The use of restraints in the elderly remains an important question
      considering the increasing number of elderly.

PMID- 29183389
TI  - Toxicological investigation of acute and chronic treatment with Gnidia
      stenophylla Gilg root extract on some blood parameters and histopathology of
      spleen, liver and kidney in mice.
AB  - BACKGROUND: In southeast Ethiopia, people locally use the roots of Gnidia
      stenophylla Gilg (Thymelaeaceae) to cure malaria and other diseases with no
      literature evidence substantiating its safety. The aim of this study was,
      therefore, to investigate the safety of the aqueous root extract of G.
      stenophylla after acute (single dose) and repeated sub chronic oral
      administration in mice. RESULTS: A single oral administration of the extract at
      500, 1000, 2000 and 4000 mg/kg body weight did not induce any behavioral change
      and mortality in both sexes. The oral LD50 of the extract was found to be above
      6000 mg/kg body weight in mice. Chronic treatment with the extract for 13 weeks
      did not induce any sign of illness and/or death and had no adverse effect on the
      body weight. Dose-related elevations of erythrocytes, hematocrit, hemoglobin,
      platelets and neutrophils differential and significant decrease in the number of
      lymphocyte were observed. Liver sections of mice treated with 800 mg/kg body
      weight, revealed mild inflammations around the portal triads and central veins;
      whereas the spleen and kidneys appeared normal with no detectable gross
      morphological and histopathological alteration at both doses. CONCLUSIONS: The
      results of this study revealed that aqueous root extract of G. stenophylla Gilg
      at antimalarial dose is safe even when taken for a longer period. At a higher
      dose, the extract may have a potential to increase some hematological indices but
      may induce mild hepatotoxicity as a side effect.

PMID- 29183390
TI  - Serum concentrations of active tamoxifen metabolites predict long-term survival
      in adjuvantly treated breast cancer patients.
AB  - BACKGROUND: Controversies exist as to whether the genetic polymorphisms of the
      enzymes responsible for the metabolism of tamoxifen can predict breast cancer
      outcome in patients using adjuvant tamoxifen. Direct measurement of
      concentrations of active tamoxifen metabolites in serum may be a more biological
      plausible and robust approach. We have investigated the association between
      CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long
      term outcome in tamoxifen treated breast cancer patients. METHODS: From an
      original observational study comprising 817 breast cancer patients, 99 women with
      operable breast cancer were retrospectively included in the present study. This
      cohort of patients were adjuvantly treated with tamoxifen, had provided serum
      samples suitable for measuring tamoxifen metabolites, and were relapse-free at 3
      years after the primary treatment commenced. The median follow-up time from this
      entry point to breast cancer death was 13.9 years. Patients were CYP2D6 genotyped
      and grouped into four CYP2D6 phenotype groups (Ultra rapid, extensive,
      intermediate, and poor metabolizers). Tamoxifen and nine metabolites were
      quantified in serum (n = 86) and compared with CYP2D6 phenotype groups and
      outcome. RESULTS: Breast cancer patients with low concentrations of Z-4-hydroxy
      tamoxifen (Z-4OHtam; <= 3.26 nM) had a breast cancer-specific survival (BCSS) of
      60% compared to 84% in patients with Z-4OHtam concentrations > 3.26 nM (p =
      0.020, log-rank hazard ratio (HR) = 3.56, 95% confidence interval (CI) = 1.14
      11.07). For patients with Z-4-hydroxy-N-desmethyl-tamoxifen (Z-endoxifen) levels
      <= 9.00 nM BCSS was 57% compared to 84% for patients with concentrations > 9.00
      nM (p = 0.029, HR = 3.73, 95% CI = 1.05-13.22). Low concentrations of Z-4OHtam
      and Z-endoxifen were associated with poorer survival also after adjusting for
      clinically relevant variables (HR = 4.27, 95% CI = 1.35-13.58, and HR = 3.70, 95%
      CI = 1.03-13.25, respectively). Overall survival analysis showed similar survival
      differences for both active metabolites. The Antiestrogen Activity Score showed
      comparable effects, but did not improve the prognostic information. CONCLUSIONS:
      Patients with Z-4OHtam and Z-endoxifen concentrations lower than 3.26 nM or 9.00
      nM, respectively, showed an adverse outcome. Our results suggest that direct
      measurement of active tamoxifen metabolite concentrations could be of clinical
      value. Validation in larger study cohorts is warranted.

PMID- 29183392
TI  - Host-specific Dactylogyrus parasites revealing new insights on the historical
      biogeography of Northwest African and Iberian cyprinid fish.
AB  - BACKGROUND: Host specificity in parasites represents the extent to which a
      parasite's distribution is limited to certain host species. Considering host
      specific parasites of primarily freshwater fish (such as gill monogeneans), their
      biogeographical distribution is essentially influenced by both evolutionary and
      ecological processes. Due to the limited capacity for historical dispersion in
      freshwater fish, their specific coevolving parasites may, through historical host
      parasite associations, at least partially reveal the historical biogeographical
      routes (or historical contacts) of host species. We used Dactylogyrus spp.,
      parasites specific to cyprinid fish, to infer potential historical contacts
      between Northwest African and European and Asian cyprinid faunas. Using
      phylogenetic reconstruction, we investigated the origin(s) of host-specific
      Dactylogyrus spp. parasitizing Northwest African and Iberian cyprinid species.
      RESULTS: In accordance with hypotheses on the historical biogeography of two
      cyprinid lineages in Northwest Africa, Barbini (Luciobarbus) and Torini
      (Carasobarbus), we demonstrated the multiple origins of Northwest African
      Dactylogyrus. Dactylogyrus spp. of Carasobarbus spp. originated from Asian
      cyprinids, while Dactylogyrus spp. of Luciobarbus spp. originated from European
      cyprinids. This indicates the historical Northern route of Dactylogyrus spp.
      dispersion to Northwest African Luciobarbus species rather than the Southern
      route, which is currently widely accepted for Luciobarbus. In addition, both
      Northwest African cyprinid lineages were also colonized by Dactylogyrus marocanus
      closely related to Dactylogyrus spp. parasitizing African Labeo spp., which
      suggests a single host switch from African Labeonini to Northwest African
      Luciobarbus. We also demonstrated the multiple origins of Dactylogyrus spp.
      parasitizing Iberian Luciobarbus species. One Iberian Dactylogyrus group was
      phylogenetically closely related to Dactylogyrus of Moroccan Carasobarbus, while
      the second was related to Dactylogyrus of Moroccan Luciobarbus. CONCLUSIONS: Our
      study confirms the different origins of two Northwest African cyprinid lineages.
      It suggests several independent historical contacts between European Iberian
      Luciobarbus and two lineages of Northwest African cyprinids, these contacts
      associated with host switches of Dactylogyrus parasites.

PMID- 29183391
TI  - Oxidative stress and cellular pathologies in Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic and progressive neurodegeneration of
      dopamine neurons in the substantia nigra. The reason for the death of these
      neurons is unclear; however, studies have demonstrated the potential involvement
      of mitochondria, endoplasmic reticulum, alpha-synuclein or dopamine levels in
      contributing to cellular oxidative stress as well as PD symptoms. Even though
      those papers had separately described the individual roles of each element
      leading to neurodegeneration, recent publications suggest that neurodegeneration
      is the product of various cellular interactions. This review discusses the role
      of oxidative stress in mediating separate pathological events that together,
      ultimately result in cell death in PD. Understanding the multi-faceted
      relationships between these events, with oxidative stress as a common denominator
      underlying these processes, is needed for developing better therapeutic
      strategies.

PMID- 29183394
TI  - Socio-demographic factors and availability of piped fountains affect food hygiene
      practice of food handlers in Bahir Dar Town, northwest Ethiopia: a cross
      sectional study.
AB  - BACKGROUND: Morbidity and mortality rates of food borne diseases are consistently
      highest in African due to poor food handling and sanitation practices. Thus, the
      study aimed to assess food handling practice and associated factors among food
      handlers of Restaurants in Bahir Dar Town, northwest, Ethiopia. A cross-sectional
      study was conducted from December, 7/2012 to January, 2/2013 among food handlers
      working in 106 restaurants in Bahir Dar Town. A structured questionnaire composed
      of socio-demographic factors, food safety knowledge, working environmental
      characteristics and food hygiene practice of food handlers was employed to
      collect the data via interviewing and observations. Binary logistic regression
      model was fitted to assess factors associated with food hygiene practice after
      multi-collinearity and outlier were checked and data was clean. Both crude odds
      ratio (COR) and adjusted odds ratio (AOR) were estimated to show the strength of
      association. In multivariate analysis, variables with a P value of <= 0.05 were
      considered as statistical significant. RESULTS: About 67.6% [95% confidence
      interval (CI) 58.8, 76.4] of food handlers had good food hygiene practice,
      whereas 32.4% of food handlers had poor food hygiene practice. The odds of having
      good food hygiene practice was higher among food handlers who had received food
      safety training [AOR: 4.7, 95% CI 1.7, 12.8], had formal education [AOR: 6.4, 95%
      CI 3.5, 11.5] and work experiences greater than 2 years [AOR: 3.4, 95% CI 1.8,
      6.4]. At last, food handlers working in restaurants which had piped fountains for
      hand wash were 2.1 times more likely to have good food hygiene practice[AOR: 2.1,
      95% CI 1.1, 3.8]. CONCLUSION: In this study, the overall food hygiene practice of
      food handlers is not to the acceptable level. Therefore, endeavors ought to be
      reinforced to improve food hygiene practices of food handlers through
      intervention programs such as training and education. Also emphasis should be
      given on the accessibility of piped fountains for the better food handling
      practice of food handlers.

PMID- 29183393
TI  - Prophylactic penehyclidine inhalation for prevention of postoperative pulmonary
      complications in high-risk patients: study protocol of a randomized controlled
      trial.
AB  - BACKGROUND: Postoperative pulmonary complications (PPCs) are major causes of
      morbidity, mortality, and prolonged hospital stay in patients after surgery.
      Using effective strategies to prevent its occurrence is essential to improve
      outcome. However, despite various efforts, the incidence of PPCs remains elevated
      in high-risk patients. Anticholinergic inhalation is used to reduce high airway
      resistance and improve pulmonary function; it may be helpful to decrease the risk
      of PPCs. Penehyclidine is a long-acting anticholinergic agent which selectively
      blocks M1 and M3 receptors. We hypothesize that, in high-risk patients,
      prophylactic penehyclidine inhalation may decrease the incidence of PPCs.
      METHODS: This is a randomized, double-blind, placebo-controlled trial with two
      parallel arms. A total of 864 patients at high risk of PPCs will be enrolled and
      randomized to receive prophylactic inhalation of either penehyclidine or placebo
      (water for injection). Study drug inhalation will be administered from the night
      (7 pm) before surgery until the second day after surgery, in an interval of every
      12 hours. The primary outcome is the incidence of PPCs within 30 days after
      surgery. Secondary outcomes include the time to onset of PPCs (from end of
      surgery to first diagnosis of PPCs), the number of PPCs (indicates the number of
      diagnosed individual PPCs), the incidence of postoperative extrapulmonary
      complications, the length of stay in hospital after surgery, and the 30-day all
      cause mortality. DISCUSSION: Results of the present study will provide evidence
      to guide clinical practice in using prophylactic inhalation of an anticholinergic
      to prevent PPCs in high-risk patients. TRIAL REGISTRATION: The study was
      registered prospectively in Chinese Clinical Trial Registry ( www.chictr.org.cn ,
      ChiCTR-IPC-15006603 ) on 14 May 2015 and retrospectively in ClinicalTrials.gov (
      NCT02644876 ) on 30 December 2015.

PMID- 29183395
TI  - Serotyping and antibiotic susceptibility patterns of Vibrio and Shigella isolates
      from diarrheal patients visiting a Tropical and Infectious Diseases Hospital in
      central Nepal.
AB  - BACKGROUND: Diarrheal diseases are the major infectious disease in developing
      countries like Nepal. Lack of proper sanitation and antimicrobial resistance
      gained by microbes have challenged to address diarrheal diseases in resource
      limited countries. Early diagnosis of disease and proper antibiotic treatment can
      significantly reduce the disease burden. This study was designed to determine the
      recent antimicrobial susceptibility pattern of Vibrio cholerae and Shigella spp.
      to assure the proper antibiotic treatment. Stool specimens were processed
      following microbiological protocol and identified by biochemical and serological
      tests recommended by the Clinical Laboratory Standard Institute. RESULTS: Out of
      total 640 analyzed stool samples, 50 were culture positive, among them 29 were
      Shigella spp. (64.4%) and 21 were V. cholerae (46.6%). All V. cholerae strains
      belonged to the serogroup O1 and serovar Ogawa. Among the Shigella spp., Shigella
      flexneri 17 (59%) topped the list of serotype followed by Shigella sonnei 8
      (28%), Shigella dysenteriae 3 (10%) and Shigella boydii 1 (3%) respectively. All
      the V. cholerae isolates (100%) were sensitive to cefotaxime while 71% were
      sensitive to tetracycline but 100 and 90.4% were resistance to co-trimoxazole and
      nalidixic acid respectively. Shigella isolates were mostly susceptible to
      cefotaxime (97%) while ciprofloxacin (48%) and ofloxacin (55%) were less
      effective drugs. CONCLUSIONS: These results on the prevalence of enteropathogens
      and their antibiotic resistance pattern may help to guide accurate choice of
      therapy in clinical setting. Hence, development of evidence based National
      Guidelines for the treatment of diarrhea is needed.

PMID- 29183396
TI  - Indirect estimation of the prevalence of spinal muscular atrophy Type I, II, and
      III in the United States.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is a progressive, devastating disease
      and a leading inherited cause of infant mortality. The limited population-based
      literature is confined to small regional studies. Estimates of prevalence are
      needed to characterize the burden of SMA and to understand trends in prevalence
      by disease type as new treatments become available. The reported estimates of SMA
      genotype prevalence at birth consistently range from 8.5-10.3 per 100,000 live
      births, with a mid-range estimate of 9.4 per 100,000. Among infants born with an
      SMA genotype, it is reported that ~58% will develop SMA Type I, 29% will develop
      Type II, and 13% will develop Type III, respectively. RESULTS: Using evidence
      from peer-reviewed literature for SMA birth prevalence, age at symptom onset, and
      SMA type-specific survival, and incorporating United States vital statistics, we
      constructed life tables to estimate prevalence for SMA Types I, II, and III in
      the United States. We estimated the number of prevalent cases in the US to be
      8526, 9429, and 10,333 based on a birth prevalence of 8.5, 9.4, and 10.3,
      respectively (the lower, midpoint, and upper ends of the reported range).
      Assuming the midpoint of 9.4 and US-reported survival, the type-specific
      population prevalence estimates were 1610 for SMA Type I, 3944 for SMA Type II,
      and 3875 for SMA Type III. Evidence-based estimates of the number of people
      living with SMA in the United States in the published literature were previously
      unavailable. CONCLUSIONS: In the absence of a survey or other means to directly
      estimate prevalence in the US population, estimates can be calculated indirectly
      using a life table.

PMID- 29183397
TI  - Schistosomiasis, intestinal helminthiasis and nutritional status among preschool
      aged children in sub-urban communities of Abeokuta, Southwest, Nigeria.
AB  - OBJECTIVE: Schistosomiasis and intestinal helminthiasis are major public health
      problems with school-aged children considered the most at-risk group. Pre-school
      aged children (PSAC) are excluded from existing control programs because of
      limited evidence of infections burden among the group. We assessed the prevalence
      of infections and effect on nutritional status of preschool aged children in
      Abeokuta, Southwestern Nigeria. RESULTS: A community-based cross-sectional study
      involving 241 children aged 0-71 months was conducted in 4 sub-urban communities
      of Abeokuta. Urine and faecal samples were collected for laboratory diagnosis for
      parasites ova. Nutritional status determined using age and anthropometric
      parameters was computed based on World Health Organization 2006 growth standards.
      Data were subjected to descriptive statistics analysis, Chi square, t-test and
      ANOVA. Of 167 children with complete data, 8 (4.8%) were infected with
      Schistosoma haematobium; Schistosoma mansoni 6 (3.6%); Taenia species 84 (50.3%);
      Ascaris lumbricoides 81 (48.5%) and hookworm 63 (37.7%). Overall, 46.7% of the
      children were malnourished, 39.5% stunted, 22.8% underweight and 11.4% exhibiting
      wasting/thinness. Mean values of anthropometric indices were generally lower in
      children with co-infection than those with single infection. We observed low
      level of schistosomiasis but high prevalence of intestinal helminthiasis and poor
      nutritional status that calls for inclusion of PSAC in control programs.

PMID- 29183398
TI  - An ethnographic observation study of the facilitator role in an implementation
      process.
AB  - BACKGROUND: Even though the importance of a facilitator during an implementation
      process is well described, the facilitator's role is rarely problematized in
      relation to the organizational context in terms of power and legitimacy; themes
      which have recently been brought to the fore when studying change in health care
      organizations. Therefore, in this article, we present a qualitative study with
      the aim of identifying key aspects of the experience of being in a facilitator
      role. The data collection involved ethnographic fieldwork encompassing
      observations and field notes, as well as two qualitative interviews with the
      facilitator. The data were analysed using a phenomenological hermeneutical method
      in order to formulate thematic aspects of the implementation process. The study
      was conducted in southern Sweden between January 2013 and August 2014. RESULTS:
      One main theme, "walking a tightrope", and four sub-themes, all of which involved
      balancing acts of different levels and different ways, were identified. These
      included: being in control, but needing to adjust; pushing for change, but forced
      to stand back; being accepted, but dependent; and being reasonable, but
      culturally sensitive. CONCLUSION: Instead of listing the desirable qualities and
      conditions of a facilitator, this study shows that being a facilitator can be
      described more completely by applying the concept of role, thus allowing a more
      holistic process of reflection and analysis. This in turn makes it possible to
      move from the reactive stance of balancing to a more proactive stance of
      negotiating.

PMID- 29183399
TI  - Evaluating progestogens for prevention of preterm birth international
      collaborative (EPPPIC) individual participant data (IPD) meta-analysis: protocol.
AB  - BACKGROUND: Preterm birth is the most common cause of death and harm to newborn
      babies. Babies that are born early may have difficulties at birth and experience
      health problems during early childhood. Despite extensive study, there is still
      uncertainty about the effectiveness of progestogen (medications that are similar
      to the natural hormone progesterone) in preventing or delaying preterm birth, and
      in improving birth outcomes. The Evaluating Progestogen for Prevention of Preterm
      birth International Collaborative (EPPPIC) project aims to reduce uncertainty
      about the specific conditions in which progestogen may (or may not) be effective
      in preventing or delaying preterm birth and improving birth outcomes. METHODS:
      The design of the study involves international collaborative individual
      participant data meta-analysis comprising systematic review, re-analysis, and
      synthesis of trial datasets. Inclusion criteria are as follows: randomized
      controlled trials comparing progestogen versus placebo or non-intervention, or
      comparing different types of progestogen, in asymptomatic women at risk of
      preterm birth. Main outcomes are as follows; fetal/infant death, preterm birth or
      fetal death (<=37 weeks, <=34 weeks, <= 28 weeks), serious neonatal complications
      or fetal/infant death, neurosensory disability (measured at 18 months or later)
      or infant/child death, important maternal morbidity, or maternal death. In
      statistical methods, IPD will be synthesized across trials using meta-analysis.
      Both 'two-stage' models (where effect estimates are calculated for each trial and
      subsequently pooled in a meta-analysis) and 'one-stage' models (where all IPD
      from all trials are analyzed in one step, while accounting for the clustering of
      participants within trials) will be used. If sufficient suitable data are
      available, a network meta-analysis will compare all types of progesterone and
      routes of administration extending the one-stage models to include multiple
      treatment arms. DISCUSSION: EPPPIC is an international collaborative project
      being conducted by the forming EPPPIC group, which includes trial investigators,
      an international secretariat, and the research project team. Results, which are
      intended to contribute to improvements in maternal and child health, are expected
      to be publicly available in mid 2018. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42017068299.

PMID- 29183400
TI  - Predicting cancer type from tumour DNA signatures.
AB  - BACKGROUND: Establishing the cancer type and site of origin is important in
      determining the most appropriate course of treatment for cancer patients.
      Patients with cancer of unknown primary, where the site of origin cannot be
      established from an examination of the metastatic cancer cells, typically have
      poor survival. Here, we evaluate the potential and limitations of utilising gene
      alteration data from tumour DNA to identify cancer types. METHODS: Using
      sequenced tumour DNA downloaded via the cBioPortal for Cancer Genomics, we
      collected the presence or absence of calls for gene alterations for 6640 tumour
      samples spanning 28 cancer types, as predictive features. We employed three
      machine-learning techniques, namely linear support vector machines with recursive
      feature selection, L 1-regularised logistic regression and random forest, to
      select a small subset of gene alterations that are most informative for cancer
      type prediction. We then evaluated the predictive performance of the models in a
      comparative manner. RESULTS: We found the linear support vector machine to be the
      most predictive model of cancer type from gene alterations. Using only 100
      somatic point-mutated genes for prediction, we achieved an overall accuracy of
      49.4+/-0.4 % (95 % confidence interval). We observed a marked increase in the
      accuracy when copy number alterations are included as predictors. With a
      combination of somatic point mutations and copy number alterations, a mere 50
      genes are enough to yield an overall accuracy of 77.7+/-0.3 %. CONCLUSIONS: A
      general cancer diagnostic tool that utilises either only somatic point mutations
      or only copy number alterations is not sufficient for distinguishing a broad
      range of cancer types. The combination of both gene alteration types can
      dramatically improve the performance.

PMID- 29183401
TI  - Primary replication and invasion of the bovine gammaherpesvirus BoHV-4 in the
      genital mucosae.
AB  - Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that is widespread in cattle.
      Ex vivo models with bovine genital tract mucosa explants were set up to study
      molecular/cellular BoHV-4-host interactions. Bovine posterior vagina, cervix and
      uterus body were collected from cows at two stages of the reproductive cycle for
      making mucosa explants. The BoHV-4 replication kinetics and characteristics
      within the three different mucosae of animals in the follicular and luteal phase
      were assessed by virus titration. The number of plaques, plaque latitude and
      number of infected cells were determined by immunofluorescence. BoHV-4 replicated
      in a productive way in all genital mucosal tissues. It infected single individual
      cells in both epithelium and lamina propria of the genital mucosae at 24 hours
      post-inoculation (hpi). Later, small BoHV-4 epithelial plaques were formed that
      did not spread through the basement membrane. 50% of the number of BoHV-4
      infected cells were identified as cytokeratin+ and CD172a+ cells in the three
      parts of the genital tract at 24 hpi. Upon a direct injection of genital explants
      with BoHV-4, fibrocytes became infected, indicating that the unidentified 50% of
      the infected cells are most probably fibrocytes. In this study, in vivo-related
      in vitro genital tract models were successfully established and the early stage
      of the pathogenesis of a genital infection was clarified: BoHV-4 starts with a
      productive infection of epithelial cells in the reproductive tract, forming small
      foci followed by a non-productive infection of surveilling monocytic cells which
      help BoHV-4 to invade into deeper tissues.

PMID- 29183404
TI  - Prolonged prostaglandin-E2-associated periosteal reaction and elevated C-reactive
      protein levels.
AB  - This is a case review of two infants who received a prolonged course of
      prostaglandin-E2 therapy for congenital cardiac lesions while awaiting corrective
      surgery. These cases highlight an association between prolonged prostaglandin-E2
      therapy with periosteal reactions and elevated C-reactive protein levels. Failure
      to recognise this association may lead to multiple courses of antibiotics for
      presumed sepsis and further prolongation of prostaglandin-E2 therapy.

PMID- 29183402
TI  - Two sides of the same coin? Unraveling subtle differences between human embryonic
      and induced pluripotent stem cells by Raman spectroscopy.
AB  - BACKGROUND: Human pluripotent stem cells, including embryonic stem cells and
      induced pluripotent stem cells, hold enormous promise for many biomedical
      applications, such as regenerative medicine, drug testing, and disease modeling.
      Although induced pluripotent stem cells resemble embryonic stem cells both
      morphologically and functionally, the extent to which these cell lines are truly
      equivalent, from a molecular point of view, remains controversial. METHODS:
      Principal component analysis and K-means cluster analysis of collected Raman
      spectroscopy data were used for a comparative study of the biochemical
      fingerprint of human induced pluripotent stem cells and human embryonic stem
      cells. The Raman spectra analysis results were further validated by conventional
      biological assays. RESULTS: Raman spectra analysis revealed that the major
      difference between human embryonic stem cells and induced pluripotent stem cells
      is due to the nucleic acid content, as shown by the strong positive peaks at 785,
      1098, 1334, 1371, 1484, and 1575 cm-1, which is enriched in human induced
      pluripotent stem cells. CONCLUSIONS: Here, we report a nonbiological approach to
      discriminate human induced pluripotent stem cells from their native embryonic
      stem cell counterparts.

PMID- 29183405
TI  - Socio-economic factors associated with an increase in fruit and vegetable
      consumption: a 12-year study in women from the E3N-EPIC study.
AB  - OBJECTIVE: To identify individual and contextual socio-economic factors
      associated with an increase in fruit and vegetable (F&V) consumption over a 12
      year period and evaluate if some socio-economic factors were differentially
      associated with the change in consumption of some types of F&V. DESIGN:
      Associations between increased F&V consumption and socio-economic factors were
      studied with multivariate logistic regression. SETTING: E3N, a French prospective
      cohort study of 98 995 women. SUBJECTS: E3N participants (n 58 193) with
      information on diet in 1993 and 2005, and numerous individual and contextual
      socio-economic factors available. RESULTS: Associations between some individual
      socio-economic factors and changes in F&V consumption were observed. For
      instance, women who lived in a large household (>3 children v. no child) had
      higher probability of increasing their vegetable consumption (OR=1.33; 95 % CI
      1.24, 1.42). This association was driven by higher consumption of courgette and
      raw cucumber. Living with a partner was associated with higher odds of increasing
      consumption of fruits (OR=1.07; 95 % CI 1.02, 1.13) such as pear, peach and
      grape. CONCLUSIONS: Certain individual socio-economic factors, but none of the
      contextual socio-economic factors examined, were associated with an increase in
      F&V consumption. Factors associated with an increase in total F&V consumption
      were not necessarily associated with an increase in fruit or vegetable
      consumption separately, or with an increase in each subtype of fruit or
      vegetable. Magnitudes of the different associations observed also differed when
      F&V were considered together, separately or by subtype. Increases in F&V
      consumption were mostly observed in women with high socio-economic position. To
      develop effective nutritional interventions and policies that take the socio
      economic environment of individuals into account, we recommend future research to
      further focus on (i) pathways through which population characteristics might
      influence changes in F&V consumption and (ii) existing interactions between
      individual and contextual socio-economic factors.

PMID- 29183406
TI  - Coping Strategies in Mothers of Children with Intellectual Disabilities Showing
      Multiple Forms of Challenging Behaviour: Associations with Maternal Mental
      Health.
AB  - BACKGROUND: It is well documented that mothers of children with intellectual
      disabilities experience elevated mental health difficulties and that these are
      exacerbated by the presence of challenging behaviour. However, comparatively
      little is known about the effect of specific coping strategies for managing such
      behaviours. AIMS: This paper aims to document coping strategies used by mothers
      of children showing multiple forms of challenging behaviour and to explore how
      these relate to positive and negative maternal mental health. METHOD: Eighty-nine
      mothers of children with intellectual disabilities completed questionnaires
      assessing maternal mental health (Hospital Anxiety and Depression Scale, Positive
      and Negative Affect Scale) and maternal coping strategies (Brief COPE). RESULTS:
      Coping strategies were not associated with child age or ability, but were
      associated with maternal mental health. Higher levels of problem- and positive
      coping strategies were associated with higher positive affect. Although active
      avoidance coping was the least frequently reported, it was associated with higher
      levels of negative affect and increased anxiety and depression. Moderated
      mediation analyses identified that active-avoidance coping mediated the
      relationship between the number of forms of challenging behaviour and poor
      maternal mental health, but only in mothers with lower levels of problem-focused
      coping. CONCLUSIONS: Active-avoidance coping is associated with poorer negative
      mental health in mothers of children with intellectual disabilities who have
      average to low levels of problem-focused coping. This is reflective of that noted
      within a range of populations, highlighting it as a key area for intervention.

PMID- 29183407
TI  - Phage-mediated dissemination of virulence factors in pathogenic bacteria
      facilitated by antibiotic growth promoters in animals: a perspective.
AB  - Addition of sub-therapeutic antibiotics to the feed of food-producing animals for
      growth promotion and disease prevention has become a common agricultural practice
      in many countries. The emergence of antibiotic-resistant pathogens is a looming
      concern associated with the use of antibiotic growth promoters (AGPs) around the
      world. In addition, some studies have shown that AGPs may not only affect
      antibiotic resistance but may also stimulate the dissemination of virulence
      factors via bacteriophages. Although only a few studies are currently available
      in the literature regarding this topic, in this article we endeavor to provide a
      perspective about how AGPs would impact the transmission of virulence factors by
      horizontal gene transfer via phages in a few pathogenic bacterial species
      significant to livestock production.

PMID- 29183403
TI  - Linkage, whole genome sequence, and biological data implicate variants in RAB10
      in Alzheimer's disease resilience.
AB  - BACKGROUND: While age and the APOE epsilon4 allele are major risk factors for
      Alzheimer's disease (AD), a small percentage of individuals with these risk
      factors exhibit AD resilience by living well beyond 75 years of age without any
      clinical symptoms of cognitive decline. METHODS: We used over 200 "AD resilient"
      individuals and an innovative, pedigree-based approach to identify genetic
      variants that segregate with AD resilience. First, we performed linkage analyses
      in pedigrees with resilient individuals and a statistical excess of AD deaths.
      Second, we used whole genome sequences to identify candidate SNPs in significant
      linkage regions. Third, we replicated SNPs from the linkage peaks that reduced
      risk for AD in an independent dataset and in a gene-based test. Finally, we
      experimentally characterized replicated SNPs. RESULTS: Rs142787485 in RAB10
      confers significant protection against AD (p value = 0.0184, odds ratio =
      0.5853). Moreover, we replicated this association in an independent series of
      unrelated individuals (p value = 0.028, odds ratio = 0.69) and used a gene-based
      test to confirm a role for RAB10 variants in modifying AD risk (p value = 0.002).
      Experimentally, we demonstrated that knockdown of RAB10 resulted in a significant
      decrease in Abeta42 (p value = 0.0003) and in the Abeta42/Abeta40 ratio (p value
      = 0.0001) in neuroblastoma cells. We also found that RAB10 expression is
      significantly elevated in human AD brains (p value = 0.04). CONCLUSIONS: Our
      results suggest that RAB10 could be a promising therapeutic target for AD
      prevention. In addition, our gene discovery approach can be expanded and adapted
      to other phenotypes, thus serving as a model for future efforts to identify rare
      variants for AD and other complex human diseases.

PMID- 29183408
TI  - Prevalence and temporal trend (2005-2015) of anaemia among children in Northeast
      Brazil.
AB  - OBJECTIVE: Anaemia is the main nutritional deficiency in Brazil, and a prevention
      and control programme (National Program for Iron Supplementation) has been
      developed since 2005. Studies on the temporal evolution of anaemia prevalence
      contribute to assessment of the effectiveness of the actions undertaken. The
      present study aimed to identify the prevalence and temporal trend of anaemia in
      children. DESIGN: Study based on two cross-sectional household surveys carried
      out in 2005 and 2015. Anaemia was defined as Hb<11 g/dl (HemoCue(r)). Trend
      analysis was performed using the prevalence ratio (PR), calculated by Poisson
      regression with a robust adjustment of the variance. Differences were significant
      when P<0.05 in both crude analyses and those adjusted for possible confounding
      factors (e.g. socio-economic, demographic and health variables). SETTING:
      Alagoas, Brazil. SUBJECTS: In total, 666 and 782 children in the first and second
      Alagoas State Health and Nutrition Survey, respectively (probabilistic samples).
      RESULTS: In 2005 and 2015, anaemia prevalence was 45.1 and 27.4 %, respectively (
      39.1 %; PR=0.61; 95 % CI 0.52, 0.70). In both surveys, children aged <=24 months
      were more affected (P24 months (67.2 v. 40.7 %; 27.0 v. 19.3 %, respectively).
      CONCLUSIONS: The prevalence of anaemia reduced significantly in the evaluated
      period. Thus, it may no longer be a severe public health problem but can instead
      be considered a problem of moderate magnitude. It remains, however, above the
      level considered acceptable according to WHO criteria. These results justify the
      implementation of prevention and control actions.

PMID- 29183409
TI  - Genetic risk of major depressive disorder: the moderating and mediating effects
      of neuroticism and psychological resilience on clinical and self-reported
      depression.
AB  - BACKGROUND: Polygenic risk scores (PRS) for depression correlate with depression
      status and chronicity, and provide causal anchors to identify depressive
      mechanisms. Neuroticism is phenotypically and genetically positively associated
      with depression, whereas psychological resilience demonstrates negative
      phenotypic associations. Whether increased neuroticism and reduced resilience are
      downstream mediators of genetic risk for depression, and whether they contribute
      independently to risk remains unknown. METHODS: Moderating and mediating
      relationships between depression PRS, neuroticism, resilience and both clinical
      and self-reported depression were examined in a large, population-based cohort,
      Generation Scotland: Scottish Family Health Study (N = 4166), using linear
      regression and structural equation modelling. Neuroticism and resilience were
      measured by the Eysenck Personality Scale Short Form Revised and the Brief
      Resilience Scale, respectively. RESULTS: PRS for depression was associated with
      increased likelihood of self-reported and clinical depression. No interaction was
      found between PRS and neuroticism, or between PRS and resilience. Neuroticism was
      associated with increased likelihood of self-reported and clinical depression,
      whereas resilience was associated with reduced risk. Structural equation
      modelling suggested the association between PRS and self-reported and clinical
      depression was mediated by neuroticism (43-57%), while resilience mediated the
      association in the opposite direction (37-40%). For both self-reported and
      clinical diagnoses, the genetic risk for depression was independently mediated by
      neuroticism and resilience. CONCLUSIONS: Findings suggest polygenic risk for
      depression increases vulnerability for self-reported and clinical depression
      through independent effects on increased neuroticism and reduced psychological
      resilience. In addition, two partially independent mechanisms - neuroticism and
      resilience - may form part of the pathway of vulnerability to depression.

PMID- 29183410
TI  - Trophic relationship between the invasive parasitic copepod Mytilicola orientalis
      and its native blue mussel (Mytilus edulis) host.
AB  - Invasive parasites can spill over to new hosts in invaded ecosystems with often
      unpredictable trophic relationships in the newly arising parasite-host
      interactions. In European seas, the intestinal copepod Mytilicola orientalis was
      co-introduced with Pacific oysters (Magallana gigas) and spilled over to native
      blue mussels (Mytilus edulis), with negative impacts on the condition of infected
      mussels. However, whether the parasite feeds on host tissue and/or stomach
      contents is yet unknown. To answer this question, we performed a stable isotope
      analysis in which we included mussel host tissue and the primary food sources of
      the mussels, microphytobenthos (MPB) and particulate organic matter (POM). The
      copepods were slightly enriched in delta15N (mean Delta15N +/- s.d.; 1.22 +/-
      0.580/00) and delta13C (Delta13C 0.25 +/- 0.320/00) with respect to their host.
      Stable isotope mixing models using a range of trophic fractionation factors
      indicated that host tissue was the main food resource with consistent additional
      contributions of MPB and POM. These results suggest that the trophic relationship
      of the invasive copepod with its mussel host is parasitic as well as
      commensalistic. Stable isotope studies such as this one may be a useful tool to
      unravel trophic relationships in new parasite-host associations in the course of
      invasions.

PMID- 29183411
TI  - An ARV1 homologue from a filarial nematode is functional in yeast.
AB  - The transmembrane protein, ARV1, plays a key role in intracellular sterol
      homeostasis by controlling sterol distribution and cellular uptake. To date, only
      the ARV1s from yeast and humans have been characterized to some extent. In this
      study, the ARV1 of an animal filarial parasite, Setaria digitata (SdARV1), was
      characterized; its cDNA was 761 bp and encoded a protein of 217 amino acids, with
      a predicted molecular weight of 25 kDa, containing a highly conserved ARV1
      homology domain and three transmembrane domains in the bioinformatic analyses.
      Information required to cluster members belonging to a particular taxon has been
      revealed in phylogenetic analyses of ARV1 sequences derived from different
      organisms. Reverse transcription-polymerase chain reaction (RT-PCR) analyses
      indicated that SdARV1 was expressed in different developmental stages -
      microfilariae and adult male and female worms. Experiments carried out with a
      single copy of the SdARV1 under the control of the PMA-1 promoter in a
      temperature-sensitive Saccharomyces cerevisiae mutant strain indicated full
      complementation of the mutant phenotype, with growth at a non-permissive
      temperature (37 degrees C). Microscopic observations of cellular morphology with
      Gram staining revealed alteration of the shape from shrunken to oval, in mutant
      and complemented strains, respectively. Assessment of free sterol levels
      extracted from mutant yeast and complemented strains indicated that the level of
      sterol was significantly higher in the former compared to the latter, which had
      sterol levels similar to those of the wild type. Thus, the results of the current
      study suggest that SdARV1 is ubiquitously expressed in different developmental
      stages of S. digitata, and that it is a true functional homologue of mammalian
      and yeast ARV1s, which have crucial phylogenetic information that follows
      classical evolutionary trends. Finally, this is the first study to report the
      biological function of nematode ARV1.

PMID- 29183412
TI  - Impact of sexual maturity on the welfare of immunocastrated v. entire heavy
      female pigs.
AB  - During oestrus, fattening female pigs are more prone to lameness, fractures and
      wounds due to mounting and agonistic behaviours of penmates. This study assessed
      the effect of sexual maturity on the behaviour and welfare of heavy female pigs
      slaughtered at 36 weeks of age (180+/-10 kg) for dry-cured ham production. An
      immunocastrated control group was used for comparison. In all, 56 15-week-old
      female pigs, individually identifiable by back tattoos were equally distributed
      among four pens. All animals from two pens were subject to a three-dose
      immunocastration schedule at 16, 20 and 32 weeks of age. Skin lesions and
      behaviours were assessed at 18, 23, 28, 33 and 36 weeks of age. A blood sample
      was collected at 20, 24, 28 and 32 weeks of age for assessing health/stress
      parameters and GnRH antibodies. At slaughter, ovaries were weighed, measured and
      histologically examined; stomachs, carcasses and lungs were scored for lesions
      and a further blood sample was taken. Immunocastrated pigs did not significantly
      differ from controls in growth rate, feed efficiency and slaughter performances
      (lung score, gastric score, backfat thickness). However, they showed a lower
      frequency of aggressive interactions at 33 and 36 weeks, lower front lesions at
      28 weeks, but higher at 30 weeks; a lower haptoglobin level at 28 weeks, a lower
      level of cortisol and back lesions at slaughter (36 weeks). These findings
      suggest a low, yet not negligible, impact of sexual maturity on the welfare of
      heavy female pigs.

PMID- 29183413
TI  - Pathogens collections, biobanks and related-data in a One Health legal and
      ethical perspective.
AB  - Research on emerging infectious diseases calls for a work on collections of
      pathogens (including hosts or vectors from which the pathogens were isolated),
      related to human and animal health, to wildlife or on the environmental material.
      In this respect, the adoption of a One Health perspective is determined by the
      need for a common approach to consider the collection, storage and use of
      pathogens coming from human or non-human sources, and particularly when the same
      pathogen is taken from different environments. In response to this development,
      our purpose is to delineate a flexible regulation framework concerning
      collections of pathogens from various origins or hosts and their associated data
      in order to facilitate scientific work and research partnerships. The legal and
      ethical cutting-edge research on Biomedical Big Data is particularly stimulating
      when it comes to address challenges related to collections or biobanks of
      pathogens such as prior informed consent and accessibility, Material Transfer
      Agreement or benefit sharing.

PMID- 29183414
TI  - Effects of soluble fiber inclusion in gestation diets with varying fermentation
      characteristics on lactational feed intake of sows over two successive parities.
AB  - The effects of soluble fiber inclusion in gestation diets with varying
      fermentation characteristics (fermentation kinetics and short-chain fatty acids
      (SCFA)-profile) on lactational feed intake of sows and their piglet growth over
      two parities were investigated using an in vitro-in vivo methodology. After
      breeding, 90 multiparous Landrace sows were randomized to one of three
      experimental diets: the control (CON) diet, konjac flour (KF) diet or sugar beet
      pulp (SBP) diet. All diets had similar levels of net energy, CP, insoluble fiber
      and NDF, but KF and SBP diets had higher soluble fiber levels than the CON diet.
      During gestation, the sows were restrictively fed with three different diets, but
      during lactation, all the sows were similarly fed ad libitum. The three gestation
      diets were enzymatically hydrolyzed using pepsin and pancreatin, and enzymolyzed
      residues were used in in vitro fermentation. Gas and SCFA production were
      monitored during fermentation. After fermentation, enzymolyzed residues of KF or
      SBP diets resulted in higher final asymptotic gas volume than those of the CON
      diet. The enzymolyzed residues of KF diet were mainly part of rapidly fermented
      fractions, whereas those of SBP diet were mainly part of slowly fermented
      fractions. In addition, the acetic acid, butyric acid and total SCFA
      concentrations of enzymolyzed residues of KF diet were higher (P<0.01) than the
      control and SBP diets. In the in vivo studies, on day 90 of gestation, the KF
      diet sows had higher plasma SCFA concentration (P<0.05) at 4 h after feeding than
      the CON diet sows. Furthermore, the KF diet sows had lower plasma free fatty acid
      (FFA) concentration (P<0.01) at 4 h after feeding, and a lower value of
      homeostasis model assessment (HOMA)-insulin resistance (P<0.05), but a higher
      value of HOMA-insulin sensitivity (P<0.01). The KF diet sows also consumed more
      feed during lactation (P<0.01) and weaned significantly heavier pigs (P<0.01)
      than the CON diet sows. The overall results showed that the high fermentation
      capacity KF diet contributed to an increased lactational feed intake and improved
      performance of piglets in the second reproductive cycle.

PMID- 29183415
TI  - The pre-participation screening in young athletes: which protocol do we need
      exactly?
AB  - The aim was to assess the utility and feasibility of a comprehensive cardiac
      screening protocol in young athletes before participation in sports. A total of
      380 athletes referring before participation in sports, between April, 2014 and
      April, 2015, were included in this study. The mean age was 12.4 years. A
      screening protocol has been applied to all, including personal and family
      history, physical examination, 12-lead electrocardiography, transthoracic
      echocardiography, 24-hour rhythm Holter analysis, and treadmill exercise test.
      The most frequent complaints were chest pain in 19 (5%), dyspnoea in 13 (3.4%),
      and dizziness and fainting in five patients (1.3%) on exercise. There was sudden
      death and arrhythmia in 41 patients (10.7%) owing to family history. Heart murmur
      was present in 20 (5.2%) and hypertension in 10 patients (2.6%) on physical
      examination. The 12-lead electrocardiography was abnormal in 9 patients (2.4%).
      The findings of transthoracic echocardiography were insignificant in 47 patients
      (12.3%) and in five patients (1.3%) a haemodynamically important condition was
      detected. The 24-hour rhythm Holter analysis was abnormal in six patients (1.5%).
      There were significant ST changes in two patients (0.5%) on treadmill exercise
      test with normal findings on myocardial perfusion scans. No significant relation
      was present between findings of screening protocol and transthoracic
      echocardiography, 24-hour rhythm Holter analysis, or treadmill exercise test
      results. Pre-participation screening in young athletes should consist of a
      targeted personal history, family history, physical examination, and 12-lead
      electrocardiography. Other tests should be applied only if the screening
      indicates the presence of a cardiovascular disease.

PMID- 29183416
TI  - Repair of interrupted aortic arch using autologous pulmonary artery tissue.
AB  - There are several options for the repair of interrupted aortic arch. Direct
      anastomosis may cause several problems including anastomotic site stenosis, left
      main bronchus compression, and acute-angled aortic arch. Interposition of a
      prosthetic graft has no growth potential. We present a case of 34-month-old child
      with interrupted aortic arch, which was repaired using a pulmonary autograft
      tube.

PMID- 29183417
TI  - Neurological soft signs significantly differentiate schizophrenia patients from
      healthy controls.
AB  - OBJECTIVE: Neurological soft signs (NSS) are a group of minor non-localisable
      neurological abnormalities found more often in patients with schizophrenia. The
      aim of the current study was to test for the effect of gender, age, parental age,
      age at onset and clinical symptomatology on NSS.Material and methodsThe study
      sample included 133 patients suffering from schizophrenia according to DSM-IV-TR
      (77 males and 56 females; aged 33.55+/-11.22 years old) and 122 normal controls
      (66 males and 56 females; aged 32.89+/-9.91 years old). The assessment included
      the Neurological Evaluation Scale (NES), and a number of scales assessing the
      clinical symptoms and adverse effects especially extrapyramidal. The statistical
      analysis included exploratory t-test, simple linear regression analysis, analysis
      of covariance and the calculation of correlation coefficients. RESULTS: The
      results of the current study confirm that NSS are more frequent in patients with
      schizophrenia in comparison with normal controls (Wilks=0.622, p<0.0001), but do
      not support an effect of gender, age, age at onset, paternal or maternal age,
      education, medication status or clinical subtype of schizophrenia on NES
      scores.DiscussionOverall these results suggest that NSS constitute an independent
      (from the rest of symptoms), core (present in the vast majority of patients) and
      trait (unrelated to age and probably to the stage of schizophrenia) symptom of
      schizophrenia which could be of value in the clinical assessment and research of
      schizophrenia. Overall these results are not in full accord with the literature,
      but they could serve to fill in gaps and inconsistencies observed so far.

PMID- 29183418
TI  - Defending psychiatry or defending the trivial effects of therapeutic
      interventions? A citation content analysis of an influential paper.
AB  - AIMS: Leucht et al. in 2012 described an overview of meta-analyses of the
      efficacy of medication in psychiatry and general medicine, concluding that
      psychiatric drugs were not less efficacious than other drugs. Our goal was to
      explore the dissemination of this highly cited paper, which combined a thought
      provoking message with a series of caveats. METHODS: We conducted a prospectively
      registered citation content analysis. All papers published before June 1st citing
      the target paper were independently rated by two investigators. The primary
      outcome coded dichotomously was whether the citation was used to justify a small
      or modest effect observed for a given treatment. Secondary outcomes regarded
      mentioning any caveats when citing the target paper, the point the citation was
      making (treatment effectiveness in psychiatry closely resembles that in general
      medicine, others), the type of condition (psychiatric, medical or both), specific
      disease, treatment category and specific type. We also extracted information
      about the type of citing paper, financial conflict of interest (COI) declared and
      any industry support. The primary analysis was descriptive by tabulating the
      extracted variables, with numbers and percentages where appropriate. Co
      authorship networks were constructed to identify possible clusters of citing
      authors. An exploratory univariate logistic regression was used to explore the
      relationship between each of a subset of pre-specified secondary outcomes and the
      primary outcome. RESULTS: We identified 135 records and retrieved and analysed
      120. Sixty-three (53%) quoted Leucht et al.'s paper to justify a small or modest
      effect observed for a given therapy, and 113 (94%) did not mention any caveats.
      Seventy-two (60%) used the citation to claim that treatment effectiveness in
      psychiatry closely resembles that in general medicine; 110 (91%) paper were about
      psychiatric conditions. Forty-one (34%) papers quoted it without pointing towards
      any specific treatment category, 28 (23%) were about antidepressants, 18 (15%)
      about antipsychotics. Forty (33%) of the citing papers included data. COIs were
      reported in 55 papers (46%). Univariate and multivariate regressions showed an
      association between a quote justifying small or modest effects and the point that
      treatment effectiveness in psychiatry closely resembles that in general medicine.
      CONCLUSIONS: Our evaluation revealed an overwhelmingly uncritical reception and
      seemed to indicate that beyond defending psychiatry as a discipline, the paper by
      Leucht et al. served to lend support and credibility to a therapeutic myth:
      trivial effects of mental health interventions, most often drugs, are to be
      expected and therefore accepted.Protocol registration: https://osf.io/9dqat/.

PMID- 29183419
TI  - South African guideline on deep brain stimulation for Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease,
      associated with severe impairment of quality of life. Although the motor aspects
      of the illness are typically successfully treated with medications acting on the
      dopaminergic system, a number of patients encounter progressive difficulties
      associated with their medical treatment. RECOMMENDATIONS: Carefully selected
      patients will benefit from deep brain stimulation (DBS) treatment for their PD.
      Selection requires dopamine challenge testing and neuropsychological testing for
      the presence of cognitive impairment. Careful follow-up and programming of the
      DBS system are mandatory, and a major reason for DBS failure is inadequate
      programming and management of medication. CONCLUSION: DBS is a useful component
      of standard therapy for PD and may reduce symptoms, improve quality of life,
      promote patient independence and reduce healthcare costs by reducing requirements
      for medicine.

PMID- 29183422
TI  - Congenital vascular anomalies of the liver.
AB  - Congenital vascular anomalies of the liver include a range of malformations of
      the portal venous, hepatic arterial and venous systems. Congenital portosystemic
      shunts and arteriovenous malformations make up the two most frequent such
      malformations. While infantile haemangiomas of the liver, endothelial tumours
      characterised by vascular proliferation should also be considered, as a
      proportion of them form prenatally. Evidence to support treatment strategies for
      these infants and children has been mainly based on small case series. In this
      review, we explore classification, clinical presentation, investigation and
      treatment strategies.

PMID- 29183423
TI  - Outcomes of Kasai hepatoportoenterostomy in children with biliary atresia in
      Johannesburg, South Africa.
AB  - BACKGROUND: Without timely surgical intervention, most children with biliary
      atresia (BA) are not expected to live beyond 2 years of age. The initial
      intervention, the Kasai hepatoportoenterostomy (KPE), aims to achieve biliary
      drainage. Liver transplantation (LT) is performed if jaundice fails to clear or
      when biliary cirrhosis occurs. In under-resourced South African (SA) academic
      state hospitals, KPE procedures are the standard of care for the majority of
      children with BA, but LT is becoming more routinely available. OBJECTIVES: To
      describe the outcomes of children with BA undergoing KPE, and to identify
      presenting clinical, laboratory and histological features that were associated
      with a more favourable outcome. METHODS: All children with BA who underwent KPE
      between January 2009 and June 2012 at the Johannesburg academic-hospital complex
      were included. Clinical and laboratory parameters, including paediatric end-stage
      liver disease (PELD) score at the time of KPE, liver histology fibrosis score,
      clearance of jaundice at 6 months and 24-month survival were determined. RESULTS:
      Of 70 children with BA diagnosed during the study period, 43 (61.4%) underwent
      KPE, but only 12 (27.9%) achieved early resolution of jaundice. By 24 months, 14
      (32.6%) of 43 children undergoing KPE were alive with their native liver, and 2
      (4.7%) other children underwent LT. PELD score <15 and early resolution of
      jaundice, but not age at surgery or histological fibrosis score, predicted a
      favourable outcome. CONCLUSION: Children with BA undergoing KPE in SA state
      hospitals have a poor prognosis. The PELD score at the time of KPE best predicts
      24-month survival.

PMID- 29183424
TI  - Surgery for portal hypertension in children: A 12-year review.
AB  - BACKGROUND: Portal hypertension is a common and potentially devastating condition
      in children. Notwithstanding advances in the nonsurgical management of portal
      hypertension, surgery remains an important treatment modality in select patients.
      We report here on our experience in the past 12 years. OBJECTIVES: To describe
      the profile of, indication for, and complications of shunt surgery in children
      with portal hypertension. METHODS: Twelve children underwent shunt surgery
      between 2005 and 2017. Patient records were reviewed. RESULTS: Fourteen
      procedures were performed on 12 patients during the study period. The median age
      at surgery was 6.5 (range 1 - 18) years. Six patients were male. Gastrointestinal
      bleeding that was not amenable to endoscopic control was the most common
      indication for surgery. Portal vein thrombosis was the most common cause of
      portal hypertension in our series (n=11). Two-thirds (8/12) of all patients had
      an identifiable underlying risk factor for portal vein thrombosis. One-third of
      all patients (4/12) underwent a meso-portal bypass procedure (Rex shunt), while
      58% (7/12) were managed with a distal splenorenal shunt. All patients received
      postoperative thromboprophylaxis. We experienced a single mortality, 1 patient
      experienced shunt thrombosis that required revision shunt surgery, and 2 patients
      experienced anastomotic strictures, with one being managed with revision surgery
      and the other currently awaiting radiological venoplasty. CONCLUSIONS: Surgery is
      a safe and important tool in the management of children with non-cirrhotic portal
      hypertension and those with sufficient hepatic reserve who fail to respond to
      more conservative methods for the treatment of side effects of portal
      hypertension.

PMID- 29183425
TI  - Graft-versus-host disease in paediatric liver transplantation: A review of the
      literature.
AB  - BACKGROUND: Graft versus host disease (GvHD) is a major complication after
      haematopoietic stem-cell transplantation but much less common after solid organ
      transplant and rare after liver transplantation. Early symptoms can resemble
      viral infections or drug-reactions and thus it may be under-investigated. There
      are no standard treatment guidelines for GvHD after paediatric liver
      transplantation. OBJECTIVES: To review all cases of GvHD reported to date after
      paediatric liver transplant. METHODS: Literature review of all English-language
      full-text articles published between 1990 and 2017Results. Case series articles
      and case reports were reviewed and collated. Symptoms, diagnostic investigations,
      treatments and outcomes were described for all reported cases. CONCLUSION: GvHD
      in paediatric liver transplantation is difficult to treat and has a high
      mortality, but better recognition and understanding with novel therapies
      available offer hope for the future.

PMID- 29183426
TI  - Choledochal malformations: Lessons learnt in Johannesburg.
AB  - BACKGROUND: Choledochal malformation (CM) is a well-described and relatively rare
      condition. CMs may present on antenatal ultrasound screening, through childhood
      and into adulthood. The aetiology is not well understood but the association with
      a pancreaticobiliary malunion predisposes to the development of CMs. OBJECTIVES:
      To review the experience of CMs in the Department of Paediatric Surgery,
      University of the Witwatersrand, Johannesburg to improve our patient care for
      this population. METHODS: After institutional ethics approval, a retrospective
      record review was conducted of patients presenting with CM to the Department of
      Paediatric Surgery, Faculty of Health Sciences, University of the Witwatersrand,
      Johannesburg. All patients managed between January 2010 and May 2017 were
      included. RESULTS: A total of 35 patients underwent surgery for CMs and 2
      patients were excluded from the study owing to incomplete records. Most of our
      patients (83%) presented with jaundice and a median (interquartile range)
      bilirubin level of 167 (32 - 234) mmol/L. In our cohort of patients those with
      type IV lesions presented at a younger age and with higher bilirubin and gamma
      glutamyl transferase levels, although this finding was not statistically
      significant. CONCLUSION: Although uncommon, CMs may lead to significant morbidity
      and malignancy. Specialised care is necessary to improve longterm outcomes in
      these patients.

PMID- 29183430
TI  - Bureaucracy and clinical performance.

PMID- 29183431
TI  - A puzzling case of cryptococcal meningitis.

PMID- 29183432
TI  - Dr Mary Gordon.

PMID- 29183435
TI  - Determining need for hospitalisation: Evaluation of the utility of the CRB-65
      score in patients with community-acquired pneumonia presenting to an emergency
      department.
AB  - BACKGROUND: The CRB-65 severity of illness score, used for assessing patients
      with community-acquired pneumonia (CAP), may be of particular benefit in resource
      constrained areas, since it relies purely on clinical parameters. OBJECTIVE: To
      assess the potential accuracy of the CRB-65 score when used in deciding whether
      to hospitalise patients with CAP presenting to an emergency department (ED).
      METHODS: Prospective, observational study in an academic hospital in
      Johannesburg, South Africa. Data from adult patients with radiologically
      confirmed CAP were analysed. RESULTS: Overall, 152 patients were enrolled (79
      females, 73 males; median age 36.5 years). Several diverse criteria had been used
      by the ED doctors in admission decisions, while the CRB-65 score had been used in
      only 3/152 patients (1.6%). Overall, 68/152 patients (44.7%) had been managed as
      inpatients and 84/152 (55.3%) as outpatients. If the CRB-65 had been used as the
      sole criterion for site-of-care decisions, 107/152 patients (70.4%) would
      potentially have been managed as outpatients and 45/152 (29.6%) as inpatients.
      Achieving a stable clinical condition took longer (p=0.037) and mortality was
      higher (p<0.001) in patients with higher than lower CRB-65 scores. All five
      patients who died were inpatients. Of these, three (60.0%) would have been
      classified by the CRB-65 as having an intermediate mortality risk and two (40.0%)
      as having a high mortality risk. CONCLUSIONS: This study demonstrates the utility
      of the CRB-65 score in accurately determining the need for admission of patients
      with CAP presenting to an ED in a resource-constrained environment.

PMID- 29183436
TI  - The association of khat (Catha edulis) chewing and orodental health: A systematic
      review and meta-analysis.
AB  - BACKGROUND: It has been claimed that chewing khat (Catha edulis), a plant common
      in parts of eastern and southern Africa and the Arabian Peninsula, is associated
      with a range of orodental problems. OBJECTIVE: To provide a synthesis of the
      evidence on the association between khat chewing and orodental health. METHOD: A
      systematic review and meta-analysis of studies that reported on the association
      of khat chewing and outcomes related to orodental health identified through a
      systematic search using web-based electronic search engines. RESULTS: Nineteen
      studies were found suitable for this review. Of these, between two and five
      (based on the type of outcome measured) were suitable for meta-analysis. The rest
      were used only for qualitative synthesis. A meta-analysis of the association of
      khat chewing with mucosal white lesions, gum recession, periodontal pocketing and
      gum bleeding showed that chewing increased the odds of the respective oral
      problems. However, qualitative synthesis of the findings on the effect of khat
      chewing on oral micro-organisms showed no evidence that the practice favours the
      presence of pathogenic micro-organisms in the oral cavity - instead, it seems to
      favour the proliferation of micro-organisms compatible with orodental health.
      CONCLUSION: Khat chewing is associated with adverse orodental health outcomes.
      While literature on the topic is scarce and there is a need for generation of
      more evidence from different countries, on the basis of the evidence accumulated
      to date, public health officials and health practitioners should consider khat a
      threat to orodental health and take appropriate action.

PMID- 29183437
TI  - Investigation of adult immunodeficiency and indications for immunoglobulin
      replacement therapy.
AB  - Adults presenting with recurrent infections require an approach that allows
      exclusion of underlying immunodeficiency. While secondary causes of
      immunodeficiency are the most common, primary immunodeficiency disease (PID) may
      present for the first time in adults. Failure to consider this diagnosis in
      adults and children leads to a major diagnostic delay. Recurrent localised
      infections generally suggest an underlying anatomical rather than an immune
      defect. PIDs that are most commonly encountered include common variable
      immunodeficiency, immunoglobulin (Ig) A deficiency, and IgG subclass deficiency.
      I suggest a diagnostic approach with relevant immune tests, depending on the
      clinical picture. The essential role of vaccination with polysaccharide and
      protein antigens to evaluate B-cell functional capacity, is highlighted.
      Principles of management are provided, including indications for immunoglobulin
      replacement therapy.

PMID- 29183438
TI  - Investigation and management of primary immunodeficiency in South African
      children.
AB  - The primary immunodeficiency diseases (PIDs) are inherited, non-communicable
      diseases that cause immunological dysfunction. PIDs are seldom reported in South
      Africa (SA). Based on a mid-2013 population estimate of 52.98 million and
      assuming that the prevalence of PIDs is similar to that in well-resourced
      settings, the total number of individuals with PIDs in our country should range
      between2 850 and 45 723. However, fewer than 500 cases of PID have been reported
      in SA. Between five and 15 new, fully characterised PIDs are reported annually.
      Our understanding of the physiology of the immune system has been substantially
      enhanced by these discoveries, and consequently the international classification
      of PIDs has been updated.

PMID- 29183439
TI  - Advances in the diagnosis and management of allergic disease: Applications to
      South African practice.
AB  - There have been a number of advances in the diagnosis and management of allergic
      diseases that are relevant to South African (SA) circumstances. These are all
      published or about to be published in new guidelines that provide practical
      advice to guide SA doctors who treat patients with these conditions. The
      guidelines include those for atopic dermatitis, allergic rhinitis and food
      allergy. This article reflects the most pertinent aspects of the guidelines. It
      also provides a short summary of a new allergy diagnostic test available in SA,
      the multiplexmicroarray chip, known as the immuno-solid-phase allergen chip
      (ISAC) test. It provides component-resolved allergy testing for special
      circumstances and complex allergic problems and is certainly not required as a
      screening allergy test. Finally, this article gives an update on allergen
      immunotherapy - some patients with allergic conditions may benefit from
      immunotherapy. In SA, some forms of immunotherapy for allergic rhinitis and mild
      asthma may currently include sublingual immunotherapy.

PMID- 29183440
TI  - Recommendations for the use of immunoglobulin therapy for immunomodulation and
      antibody replacement.
AB  - Polyvalent immunoglobin, derived from pooled human plasma, can be administered
      via the intravenous, subcutaneous or intramuscular route. Therapy is standard of
      care in the treatment of a number of immune-mediated pathologies across
      disciplines. By volume, the majority is used in neurology (~40%). In primary
      immunodeficiencies, therapy reconstitutes humoral immunity at replacement doses
      (0.4 - 0.6 g/kg/month), decreasing infections, and is usually lifelong. However,
      high doses, usually 2 g/kg total dose over five days, are required for
      immunomodulation in autoimmune and inflammatory indications. A high-quality
      evidence base supports use in primary antibody failure, Guillain-Barre syndrome,
      chronic inflammatory demyelinating polyneuropathy, acute idiopathic
      thrombocytopenia, Kawasaki disease andimmunobullous diseases. Low-quality
      evidence shows benefit in many other uncommon autoimmune and immunodeficient
      conditions.In South Africa, use of immunoglobulin therapy is restricted and,
      given the cost involved, will likely remain so. Therefore, the incremental
      benefit over other forms of immunosuppression, particularly corticosteroids, must
      be assessed carefully on a case-by-case basis. In most cases, therapy will be
      second-line or 'rescue' and motivation will be required. This short review aims
      to provide clinicians with the necessary understanding of the therapy, general
      considerations for use, and evidence base and quality thereof for well
      established indications.

PMID- 29183441
TI  - Immune tolerance and immunosuppression in solid organ transplantation.
AB  - Organ transplantation is the treatment of choice for patients with end-stage
      organ failure. Most of them will require lifelong immunosuppression to prevent
      both acute and chronic rejection. T-cell recognition of the allograft major
      histocompatibility complex antigens is the central event initiating cellular
      rejection of the allograft, and subsequent full T-cell activation requires three
      signals.Immunosuppressive regimens currently used in clinical practice are
      nonspecific and target T-cell activation, clonal expansion or differentiation
      into effector T cells. While these therapeutic regimens have advanced
      considerably and one-year graft survival figures for most solid organ transplants
      (SOTs) are >90%, the long-term graft survival remains fair owing to graft loss
      from chronic rejection. The 'holy grail' of SOT is therefore the development of a
      permanent specific immune tolerance against donor allogeneic antigens without the
      long-term use of immunosuppression.

PMID- 29183442
TI  - CPD Questions.

PMID- 29183444
TI  - Liver disease in children: From neonatal jaundice to living donor liver
      transplantation.
AB  - Paediatric hepatobiliary treatment, including hepatology, paediatric surgery and
      transplantation, is classified as quaternary and tertiary care and is difficult
      to access in South Africa. A dedicated part 2 of the SAMJ presents the South
      African experience together with articles by international experts in the field.

PMID- 29183445
TI  - Paediatric liver transplantation in Johannesburg revisited: 59 transplants and
      challenges met.
AB  - BACKGROUND: A paediatric liver transplant programme was started at the Wits
      Donald Gordon Medical Centre, Johannesburg, South Africa (SA), in November 2005.
      We reported on the first 29 patients in 2012. Since then we have performed a
      further 30 transplants in 28 patients, having met the major challenge of donor
      shortage by introducing a living related donor programme and increasing the use
      of split liver grafts. OBJECTIVE: To review the Wits Donald Gordon Medical Centre
      paediatric liver transplant programme to date. We describe how the programme has
      evolved and specifically compare the outcomes of the first cohort with the most
      recent 28 patients. METHODS: Case notes of all paediatric liver transplants
      performed between 14 November 2005 and 30 June 2014 were retrospectively
      reviewed. Data were analysed for age and weight at transplantation, indication
      and type of graft. Morbidity and mortality were documented, specifically biliary
      and vascular complications. Comparison was made between Era 1 (November 2005 -
      October 2012) and Era 2 (November 2012 - June 2014). RESULTS: A total of 59
      transplants were performed in 57 patients. Age at transplantation ranged from 9
      months to 213 months (mean 82.39 months) and weight ranged from 5 kg to 62 kg
      (mean 21 kg). A total of 23 whole livers, 10 reduced-size grafts, 14 split liver
      grafts and 12 living donor liver transplants (LDLTs) were performed. Eight
      patients were referred with fulminant hepatic failure (FHF), all in Era 2. Of
      these, three patients were successfully transplanted. Of the 57 patients, 45 are
      alive and well with actuarial 1-year patient and graft survival of 85% and 84% 
      and 5-year patient and graft survival of 78% and 74%, respectively. Sixteen
      (25.42%) biliary complications occurred in 15 of our 59 transplants. Seven
      patients developed significant vascular complications. Comparing Era 1 with Era
      2, mean age at transplant decreased from 100.86 months to 64.73 months, mean
      weight from 25.2 kg to 16.9 kg, and type of graft utilised changed with a trend
      away from the use of whole livers and reduced-sized grafts to split livers and
      segment 2,3 LDLT grafts. CONCLUSION: Initially limited by a shortage of donor
      organs, we aggressively explored optimal utilisation, splitting liver grafts from
      deceased donors as often as possible and establishing an LDLT programme. This
      increased access to donor livers allowed us to include patients with FHF and to
      perform retransplantation in recipients with early graft failure. It remains to
      offer liver transplantation to the entire paediatric community in SA, in
      conjunction with the only other established paediatric liver transplant unit, at
      Red Cross War Memorial Children's Hospital in Cape Town.

PMID- 29183446
TI  - Paediatric pancreatic trauma: A review of the literature and results of a
      multicentre survey on patient management.
AB  - BACKGROUND: It is generally accepted that paediatric solid organ injury should be
      treated conservatively, unless there is haemodynamic instability unresponsive to
      resuscitation. When it comes to pancreatic trauma, there is much debate about
      appropriate management. OBJECTIVES: To review the literature and determine how
      pancreatic trauma is managed in South African (SA) tertiary institutions and
      compares with international standards. METHOD: A survey was emailed to 45
      paediatric surgical consultants working in various paediatric surgical units in
      SA, Italy, England and Australia. The questionnaire comprised two scenarios of
      isolated pancreatic trauma (grade III), the main difference between them being
      the time interval between initial injury and presentation. In the first scenario,
      the patient presented 6 hours post injury whereas in the second scenario, the
      patient presented 6 days post initial injury. The survey enquired about diagnosis
      and subsequent work-up (including preferred imaging techniques), supportive
      management (including nutrition), the various options of definitive intervention
      and follow-up procedure. RESULTS: There were 21 responders from four different
      countries. In the first scenario, 10 surgeons would operate, 8 would treat
      conservatively and 3 would perform an endoscopic retrograde
      cholangiopancreatogram (ERCP) and stent. In the second scenario, 4 surgeons would
      operation, 13 would treat conservatively and 4 would undertake ERCP with stent.
      There was no difference in management between the SA surgeons and their
      international counterparts. CONCLUSION: Management of blunt pancreatic trauma in
      SA is consistent with that reported in the literature. There is still controversy
      regarding the optimal management of pancreatic injury involving ducts. No
      absolute algorithm can be used to treat these patients. All patients should be
      treated individually and managed with an approach and techniques that are
      feasible.

PMID- 29183447
TI  - Acute liver failure and transplantation in children.
AB  - Acute liver failure (ALF) was relatively easy to recognise in the days before
      liver transplantation became available as rescue therapy, because the diagnosis
      was based on end-stage disease manifestations such as profound coagulopathy,
      jaundice, encephalopathy and cerebral edema (in a patient with no history of
      chronic liver disease). These criteria no longer help us in an era when we
      struggle to define which patients are going to progress to this end-stage picture
      in the time necessary for evaluation and listing for life-saving transplantation.
      Ideally, identifying which patients will recover spontaneously or with
      appropriate treatment would relieve the justifiable concern that some patients
      receive a transplant when, given time, they would have recovered. Currently, the
      data to guide us in avoiding death without transplantation and unnecessary
      transplantation remain elusive.   This review will focus primarily on the aspects
      that surround the decision to undertake liver transplantation in a child with
      ALF. There are many excellent chapters and journal reviews which cover specific
      medical management of ALF and its complications; therefore this will not be
      addressed in this essay.

PMID- 29183448
TI  - Liver tumours in children: Current surgical management and role of
      Transplantation.
AB  - This article reviews the current surgical management of liver tumours in children
      in the light of improved chemotherapy, surgical techniques and outcomes from
      transplantation. It is a principle of management that complete removal of a
      tumour must be achieved for cure. Neoadjuvant chemotherapy may downstage advanced
      local disease to enable safe curative tumour resection. When this is not
      achievable, transplant is indicated. Conventional indications for transplant are
      unresectable stages 3 and 4 tumours confined to the liver. With the realisation
      that lifelong immunosuppressive therapy has considerable adverse consequences,
      there has been a recent trend towards extreme and 'acrobatic' liver resection to
      avoid transplantation, but still obtain a cure. The current literature is
      reviewed in the light of these trends and our own experience.

PMID- 29183449
TI  - Controversies in choledochal malformation.
AB  - Choledochal malformations (some of which are choledochal cysts) may be
      characterised as an abnormal dilatation of the biliary tract, in the absence of
      acute obstruction. Most do appear to be of congenital origin, probably related to
      distal bile duct stenosis, and almost 15% can now be detected
      antenatally.Excision and biliary reconstruction using a Roux loop as an open
      operation is still the standard to compare against, although laparoscopic
      reconstruction is increasingly reported. This article discusses recent advances
      in the understanding of choledochal malformation aetiology and classification,
      together with the role of newer modalites of surgical treatment such as
      laparoscopic excision and biliary reconstruction. Although these are definitely
      feasible, care should be taken before dispensing with standard open techniques
      that have minimal complications and proven long-term benefit.

PMID- 29183450
TI  - Role of laparoscopy during surgery at the porta hepatis.
AB  - Minimally invasive surgery in children has evolved to the extent that complex
      procedures can be performed with safety, with comparable outcomes to open surgery
      and with the advantages of minimal scarring and less pain. In this article, we
      describe the latest laparoscopic techniques used at Juntendo University Hospital
      in Japan, for treating conditions affecting the porta hepatis, focusing on
      biliary atresia and choledochal cysts. We also summarise our postoperative
      management protocols and discuss preliminary outcomes.

PMID- 29183451
TI  - The role of interventional radiology in complications after paediatric liver
      transplantation.
AB  - Liver transplantation has become an established treatment in both adults and
      children for end-stage liver disease, acute hepatic failure and certain liver
      tumours. There is a significant rate of complications after all forms of liver
      transplantation. The interventional radiologist plays a critical role in the
      diagnosis and treatment of these complications. The use of image-guided,
      minimally invasive procedures reduces the need for surgical revision or
      retransplantation, and improves graft and patient survival rate. This article
      reviews some of the most common vascular and non-vascular complications after
      paediatric liver transplantation, and the interventional radiology techniques
      used to diagnose and treat them.

PMID- 29183452
TI  - Paediatric lver transplantation for children treated at public health facilities
      in South Africa: Time for change.
AB  - Paediatric liver transplantation (PLT) is the only therapeutic option for many
      children with end-stage chronic liver disease or irreversible fulminant hepatic
      failure and is routinely considered as a therapy by paediatric
      gastroenterologists and surgeons working in developed countries. In South Africa
      (SA), a PLT programme is available at Red Cross War Memorial Children's Hospital
      in Cape Town since November 1991, and another has rapidly developed at the Wits
      Donald Gordon Medical Centre in Johannesburg over the past decade. However, for
      most children with progressive chronic liver disease who are reliant on the
      services provided at public health facilities in SA, PLT is not an option because
      of a lack of resources in a mismanaged public health system. This article briefly
      outlines the services offered at Chris Hani Baragwanath Academic Hospital - which
      is typical of public health facilities in SA - and proposes that resources be
      allocated to establish an innovative, nationally funded centre that would enable
      greater numbers of children access to a PLT programme.

PMID- 29183453
TI  - The age-related characteristics of adults with asthma who visited emergency
      departments in Korea from 2007 to 2012.
AB  - BACKGROUND: Understanding the patterns of emergency department (ED) visits of
      patients with asthma is important for disease control and prevention of
      exacerbations. OBJECTIVE: This study aimed to investigate the characteristics of
      adult patients who visited EDs because of their asthma. METHODS: Patients with
      asthma, ages >=19 years old, who visited 117 EDs throughout Korea between January
      2007 and December 2012 were identified in the National Emergency Department
      Information System (NEDIS) data base using the International Classification of
      Disease, 10th revision, codes J45 (asthma) and J46 (status asthmaticus). RESULTS:
      A total of 97,835 adult patients with asthma visited 117 EDs throughout Korea
      during the study period. There was a slight female preponderance (male-to-female
      ratio, 1:1.09). The number of patients aged 70-79-years-old was 28,031 (28.7%),
      the highest among the patients with asthma. ED visits showed a seasonal
      distribution, with most occurring in winter and spring, followed by autumn. The
      seasonal distribution varied by age; most patients ages 19-49 years presented in
      autumn (September), whereas those patients ages >=50 years presented to the ED
      most often in winter. Overall, 65.5% of patients were admitted to the hospital,
      including 12.6% admitted to an intensive care unit (ICU). Overall, 209 patients
      (0.2%) died. The rates of hospital admission to general wards and ICUs were
      highest in those patients >=70 years old; this group also had the highest
      mortality rate. CONCLUSION: In this nationwide study, which spanned 6 years, of
      adult patients with asthma, we observed an age-specific seasonal pattern of ED
      visits. Identifying the causes of age-related deterioration and seasonal visits
      to the ED will help prevent asthma symptoms and reduce medical costs.

PMID- 29183454
TI  - Preventing congenital rubella infection in the European Region of WHO: 2010
      target.
AB  - The World Health Organisation (WHO) Regional Office for Europe has recently
      published a strategic plan and surveillance guidelines for measles and congenital
      rubella infection. The strategy prioritises measles control activities but
      encourages the introduction of rubella vaccine when measles vaccine coverage has
      reached >90 %; although, many western European countries with suboptimal measles
      vaccine coverage are already using the combined measles, mumps and rubella (MMR)
      vaccine. Women in these countries may have an especially high risk of having an
      infant with congenital rubella syndrome. WHO is seeking to improve the
      surveillance for rubella and congenital rubella syndrome as a means to obtain
      better information on the burden of these diseases and engage policy decision
      makers in the need to support the WHO European Region's strategies for rubella.

PMID- 29183455
TI  - Sentinel surveillance of HIV infection in HIV test clinics, Spain 1992-2002.
AB  - HIV infection in Spain was monitored in persons undergoing voluntary HIV testing
      in ten sentinel clinics between 1992 and 2002. Only patients on their first visit
      were considered for inclusion, and their numbers rose from 4426 in 1992 to 6649
      in 2002. Most of them recognised their risk exposure as heterosexual. The
      proportion of injecting drug users decreased from 19% to 2% of the study
      population, and the proportion of female sex workers increased from 6% to 26%.
      The number of patients diagnosed with HIV infection declined from 604 in 1992 to
      153 in 2002, and HIV prevalence fell from 13.6% to 2.3% in the same period. In
      all risk exposure categories, a decrease in HIV prevalence was observed, more
      pronounced during the first few years and stabilised in the later years. In 2002,
      the highest HIV prevalence was found in injecting drug users (IDUs) (14.2%),
      homo/bisexual men (7.5%) and individuals who had an HIV infected heterosexual
      partner (10.2%).

PMID- 29183457
TI  - International trends in salmonella serotypes 1998-2003 - a surveillance report
      from the Enter-net international surveillance network.
AB  - One of the objectives of any surveillance activity is to monitor trends in
      infections. The international surveillance network for human enteric infections,
      Enter-net, has been collecting and reporting data on laboratory-confirmed human
      salmonella infections since 1993. The number of cases identified rose in the mid
      1990s, with the peak being in 1997. This paper describes the subsequent decline
      in salmonella serotypes being reported by the national reference laboratories
      participating in the Enter-net surveillance network between 1998-2003. The total
      number of human cases of salmonellosis reported by the Enter-net participating
      countries has fallen from 220 698 to 142 891 during this period. Even at these
      reported levels salmonellosis remains a major cause of morbidity in humans.

PMID- 29183456
TI  - Strengthening early warning function of surveillance in the Republic of Serbia:
      lessons learned after a year of implementation.
AB  - The Republic of Serbia, with WHO support, has implemented an early warning system
      (ALERT) for priority communicable diseases, to complement the routine
      surveillance system which notifies individual confirmed cases. The results of its
      evaluation, conducted one year after implementation is presented here. ALERT
      relies on notification of 11 syndromes by primary care facilities. Data is
      analysed weekly at district level and transmitted to national epidemiologists.
      ALERT is perceived to be a simple and flexible tool. Acceptability is higher at
      national level than at district level. Some districts perceive ALERT as a
      parallel system poorly connected to control measures. Sensitivity of ALERT in
      detecting cases of meningitis is 93%, and 37% for cases of hepatitis.
      Retrospective analysis of ALERT data identified 9 outbreaks, 5 of which had been
      recognized by epidemiologists. ALERT was the timeliest system for detecting 4
      outbreaks identified by both systems. ALERT was useful for triggering timely
      investigation and control of outbreaks of hantavirus and salmonellosis and for
      detecting the start of the influenza season. However, ALERT did not detect
      clusters of brucellosis and tularaemia targeted by the unexplained fever
      syndrome. This evaluation underlined the need for a global review of surveillance
      activities when implementing new components such as ALERT. While control measures
      based on notification of individual confirmed cases are well understood and
      implemented, the investigation and verification process that should result from
      an increase in ALERT syndromes is not fully understood. Field epidemiology
      training programmes, such as the EPIET programme, are best suited to bring about
      this change of perspective.

PMID- 29183458
TI  - Dramatic shift in the epidemiology of Salmonella enterica serotype Enteritidis
      phage types in western Europe, 1998-2003 - results from the Enter-net
      international salmonella database.
AB  - Salmonella enterica serotype Enteritidis is the predominant salmonella serovar
      identified by the Enter-net national reference laboratories in western Europe. As
      it is the most commonly recognised serotype, it is important that phage typing is
      carried out so that outbreaks can be recognised and confirmed, and trends in
      infections identifed. Data from the Enter-net salmonella database show that there
      has been a dramatic shift between phage types identified in Europe from 1998
      2003. In 1998, the proportion of phage type (PT) 4 was 61.8%, making it the most
      frequently identified phage type in humans (21 630 cases), whereas by 2003 the
      proportion of PT4 had fallen to 32.1% (8794 cases) with other strains increasing,
      both in proportion and numbers. This paper identifies the emerging strains that
      are becoming more relevant in public health terms.

PMID- 29183459
TI  - Towards a standard HIV post exposure prophylaxis for healthcare workers in
      Europe.
AB  - Antiretroviral prophylaxis (PEP) after occupational exposure to HIV in healthcare
      workers (HCWs) is used across Europe, but not in a consistent manner. A panel of
      experts, funded by the European Commission, formulated a set of recommendations.
      When it has been decided that the characteristics of the exposure indicate the
      initiation of PEP, PEP should be started as soon as possible; initiation is
      discouraged after 72 hours. PEP should be initiated routinely with any triple
      combination of antiretrovirals approved for the treatment of HIV-infected
      patients; a two class regimen is to be preferred. The source patient's treatment
      history should be sought. Counselling, psychological support, HIV testing and
      clinical evaluation should be performed at baseline, at 6-8 weeks, and at least 6
      months post exposure. Additional clinical and laboratory monitoring at one and
      two weeks should be considered, as adherence with and tolerance of the regimen
      can highlight adverse reactions and potential toxicity. Routine HIV resistance
      tests in the source patient, and direct virus assays in the exposed HCW are not
      recommended.

PMID- 29183460
TI  - How to prevent transmission of MRSA in the open community?
AB  - In the past 20 to 30 years, methicillin-resistant Staphylococcus aureus (MRSA)
      strains have been present in hospitals and have become a major cause of hospital
      acquired infection. Methicillin resistance rates of S. aureus vary considerably
      between countries, with a high prevalence in the United States, and southern
      Europe (>20%) and a low prevalence in northern Europe (< or =5%). Community
      acquired MRSA emerged worldwide in the late 1990s. There has been great confusion
      in the literature between healthcare-associated MRSA infections occurring in the
      community in patients who are at risk of acquiring hospital MRSA (such as those
      with past history of hospital admission, immunocompromised status, etc.), and
      true CA-MRSA infections due to strains that are present in the community only.

PMID- 29183461
TI  - Rubella control in France.
AB  - In the pre-vaccination era, rubella was regarded as only a mild exanthematous
      acute viral infection of children. The devastating effects of the disease were
      first identified in the early 1940s by an Australian ophthalmologist, and further
      confirmed during the 1962-65 rubella pandemic in Europe and the United States.
      They result from the transmission of the virus by infected pregnant women to
      their fetus. The resulting congenital rubella syndrome (CRS) comprises a lengthy
      list of abnormalities. The most common ones are deafness, ocular and cardiac
      defects and mental retardation. The objective of rubella vaccination, to which
      France has subscribed, is the elimination of CRS [1].

PMID- 29183462
TI  - Epidemiology of rubella and congenital rubella syndrome in Greece, 1994-2003.
AB  - In 1993, there was a large epidemic of rubella and congenital rubella syndrome
      (CRS) in Greece. The epidemiology of rubella and CRS after 1993 is described in
      this paper using information from surveillance data and published studies and
      reports. The incidence of rubella fell sharply after 1993, but a smaller outbreak
      occurred in 1999, mainly in young adults, and four CRS cases (4.0 per 100 000
      live births) were recorded. A very high proportion of the child population in
      Greece are currently vaccinated for rubella, while teenagers are inadequately
      covered (60-80% in different studies). A substantial proportion of women of
      childbearing age are susceptible to rubella (10-20% in urban areas). This could
      lead to local or more extended outbreaks. This situation shows that a
      comprehensive preventive policy should be implemented.

PMID- 29183463
TI  - A large increase of Salmonella infections in 2003 in the Netherlands: hot summer
      or side effect of the avian influenza outbreak?
AB  - In June 2003, the Dutch national Salmonella centre reported a significant excess
      isolation rate of Salmonella Enteritidis when compared with earlier years in most
      regional public health laboratories. By the end of 2003, this amounted to an
      extra 540 laboratory confirmed cases for the whole of the Netherlands, which
      implies an estimated 7500 extra cases of gastroenteritis caused by S. Enteritidis
      in the general population, an increase of 50% on previous years. The hot summer
      could not explain the findings. Strong evidence has been found to suggest that
      the increase in importation of salmonella contaminated eggs, as a side effect of
      a concurrent avian influenza outbreak, was the most probable reason for this
      excess.

PMID- 29183464
TI  - The epidemiology of infectious syphilis in the Republic of Ireland.
AB  - In response to the increasing numbers of syphilis cases reported among men having
      sex with men (MSM) in Dublin, an Outbreak Control Team (OCT) was set up in late
      2000. The outbreak peaked in 2001 and had largely ceased by late 2003. An
      enhanced syphilis surveillance system was introduced to capture data from January
      2000. Between January 2000 and December 2003, 547 cases of infectious syphilis
      were notified in Ireland (415 were MSM). Four per cent of cases were diagnosed
      with HIV and 15.4% of cases were diagnosed with at least one other STI (excluding
      HIV) within the previous 3 months. The mean number of contacts reported by male
      cases in the 3 months prior to diagnosis was 4 (range 0-8) for bisexual contacts
      and 6 for homosexual contacts (range 1-90). Thirty one per cent of MSM reported
      having had recent unprotected oral sex and 15.9% of MSM reported having had
      recent unprotected anal sex. Sixteen per cent of cases reported having had sex
      abroad in the three months prior to diagnosis. The results suggest that risky
      sexual behaviour contributed to the onward transmission of infection in Dublin.
      The outbreak in Dublin could be seen as part of a European-wide outbreak of
      syphilis. The rates of co-infection with HIV and syphilis in Ireland are
      comparable with rates reported from other centres. There is a need to improve
      surveillance systems in order to allow real time evaluation of interventions and
      ongoing monitoring of infection trends.

PMID- 29183465
TI  - Rubella control in Italy.
AB  - In Italy, rubella vaccination has been recommended since 1972 for pre-adolescent
      girls, and since the early 1990s for all children in the second year of life.
      Nevertheless, coverage in children from 12 to 24 months of age is suboptimal
      (i.e., 56% in 1998, 78% in 2003), with wide variations among regions. As a
      result, rubella is still circulating in Italy, and in 1996 the percentage of
      women susceptible to rubella between 15 and 39 years of age was >5%. Congenital
      rubella syndrome (CRS) was a notifiable disease between 1987 and 1991, with a
      range of 8-76 cases reported annually. Since 1992, national incidence data are no
      longer available, but local reports show that CRS cases are still occurring.
      Nationwide, coordinated and uniform actions are needed to control CRS
      effectively. For this reason, the National Plan for the Elimination of Measles
      and of Congenital Rubella has recently been launched. This plan includes
      strategies aimed at increasing MMR vaccination coverage in children and specific
      control measures for congenital rubella control, i.e., improving the vaccination
      of susceptible women of childbearing age, and reintroducing national surveillance
      of CRS.

PMID- 29183466
TI  - New features of rubella in Spain: the evidence of an outbreak.
AB  - In most of western Europe the rubella vaccine coverage is high. However, prior to
      the introduction of the vaccine in Latin America, rubella susceptibility in women
      of childbearing age was 10-25%. Forty one (93%) countries in Latin America have
      adopted the rubella vaccine since 2002. The adult immigrant population in Spain
      constitutes a group of susceptibles. In February 2003, the Madrid Community
      Measles Elimination Plan detected an increase in rubella notifications in women
      who had been born in Latin America. A descriptive study was undertaken to
      characterise the outbreak. A confirmed case was a person with fever or rash and a
      positive IgM serology, and living in Madrid, between 1 December 2002 and 31 March
      2003. The secondary attack rate (SAR) per household was calculated. A total of 19
      cases of rubella were identified, 15 were confirmed and 4 were probable cases.
      Fourteen (73.7%) cases were women at childbearing age. The mean age was 25.1
      years. One pregnancy was diagnosed with a voluntary termination. Eleven (57.9%)
      cases were from Ecuador. The mean time of residence in Spain was 41 months. None
      of the cases or the 54 (78.3%) household contacts had been vaccinated against
      rubella. The SAR was 9.1%. This study showed the spread of rubella in the
      susceptible Latin American Community that is resident in Madrid. The
      interventions proposed were a vaccination programme towards immigrants, a health
      education campaign to prevent congenital rubella, and a health professional
      training programme case management.

PMID- 29183467
TI  - Eighth International Meeting of the European Laboratory Working Group on
      Diphtheria and the Diphtheria Surveillance Network - June 2004: Progress is
      needed to sustain control of diphtheria in European Region.
AB  - The Eighth International Meeting of the European Laboratory Working Group on
      Diphtheria (ELWGD) and the Diphtheria Surveillance Network (DIPNET) was held and
      co-organised with the WHO Regional Office for Europe, Copenhagen, Denmark, in
      June 2004. This article provides an international updated review of progress in
      clinical, epidemiological and microbiological aspects of diphtheria in the
      European region as presented at the meeting. It highlights the need for improved
      immunisation coverage, surveillance and epidemiological studies to sustain
      control of diphtheria in European Region.

PMID- 29183468
TI  - Proposed recommendations for the management of HIV post-exposure prophylaxis
      after sexual, injecting drug or other exposures in Europe.
AB  - Post-exposure prophylaxis (PEP) is the standard of care for a healthcare worker
      (HCW) accidentally exposed to an HIV infected source person (occupational
      exposure), but this is not the case for non-occupational exposures. Very few
      national guidelines exist for the management of non-occupational exposures to HIV
      in Europe, contrarily to the occupational ones. The administration of non
      occupational post-exposure prophylaxis (NONOPEP) for HIV may be justified by: a
      biological plausibility, the effectiveness of PEP in animal studies and
      occupational exposures in humans, efficacy in the prevention of mother to child
      HIV transmission, and cost effectiveness studies. These evidences, the similar
      risk of HIV transmission for certain non-occupational exposures to occupational
      ones, and the conflicting information about attitudes and practices among
      physicians on NONOPEP led to the proposal of these European recommendations.
      Participant members of the European project on HIV NONOPEP, funded by the
      European Commission, and acknowledged as experts in bloodborne pathogen
      transmission and prevention, met from December 2000 to December 2002 at three
      formal meetings and a two day workshop for a literature review on risk exposure
      assessment and the development of the European recommendations for the management
      of HIV NONOPEP. NONOPEP is recommended in unprotected receptive anal sex and
      needle or syringe exchange when the source person is known as HIV positive or
      from a population group with high HIV prevalence. Any combination of drugs
      available for HIV infected patients can be used as PEP and the simplest and least
      toxic regimens are to be preferred. PEP should be given within 72 hours from the
      time of exposure, starting as early as possible and lasting four weeks. All
      patients should receive medical evaluation including HIV antibody tests, drug
      toxicity monitoring and counseling periodically for at least 6 months after the
      exposure. NONOPEP seems to be a both feasible and frequent clinical practice in
      Europe. Recommendations for its management have been achieved by consensus, but
      some remain controversial, and they should be updated periodically. NONOPEP
      should never be considered as a primary prevention strategy and the final
      decision for prescription must be made on the basis of the patient-physician
      relationship. Finally, a surveillance system for these cases will be useful to
      monitor NONOPEP practices in Europe.

PMID- 29183469
TI  - Report on the first PVL-positive community acquired MRSA strain in Latvia.
AB  - Infections by community-acquired methicillin resistant Staphylococcus aureus (CA
      MRSA) have been reported worldwide. Here we present characterisation of the first
      CA-MRSA isolated in Latvia. A PVL-positive ST30-MRSA-IV strain was isolated from
      a nasal swab and the central venous catheter of a patient with fever and multiple
      organ failure. The PFGE pattern of this strain was identical to pattern SE00-3 of
      MRSA isolated in Sweden from 29 patients during 2000-2003. This strain is related
      to the South Pacific area, and its appearance in Sweden and Latvia demonstrates
      its global spread.

PMID- 29183470
TI  - Bichat guidelines for the clinical management of glanders and melioidosis and
      bioterrorism-related glanders and melioidosis.
AB  - Glanders and melioidosis are two infectious diseases that are caused by
      Burkholderia mallei and Burkholderia pseudomallei respectively. Infection may be
      acquired through direct skin contact with contaminated soil or water. Ingestion
      of such contaminated water or dust is another way of contamination. Glanders and
      melioidosis have both been studied for weaponisation in several countries in the
      past. They produce similar clinical syndromes. The symptoms depend upon the route
      of infection but one form of the disease may progress to another, or the disease
      might run a chronic relapsing course. Four clinical forms are generally
      described: localised infection, pulmonary infection, septicaemia and chronic
      suppurative infections of the skin. All treatment recommendations should be
      adapted according to the susceptibility reports from any isolates obtained. Post
      exposure prophylaxis with trimethoprim-sulfamethoxazole is recommended in case of
      a biological attack. There is no vaccine available for humans.

PMID- 29183471
TI  - Bichat guidelines for the clinical management of brucellosis and bioterrorism
      related brucellosis.
AB  - Interest in Brucella species as a biological weapon stems from the fact that
      airborne transmission of the agent is possible. It is highly contagious and
      enters through mucous membranes such as the conjunctiva, oropharynx, respiratory
      tract and skin abrasions. It has been estimated that 10-100 organisms only are
      sufficient to constitute an infectious aerosol dose for humans. Signs and
      symptoms are similar in patients whatever the route of transmission and are
      mostly non-specific. Symptoms of patients infected by aerosol are
      indistinguishable from those of patients infected by other routes. Regimens
      containing doxycycline plus streptomycin or doxycycline plus rifampin are
      effective for most forms of brucellosis. Isolation of patients is not necessary.
      Trimethoprim-sulfamethoxazole and fluoroquinolones also have good results against
      Brucella, but are associated with high relapse rates when used as monotherapy.
      The combination of ofloxacin plus rifampicin is associated with good results.
      Even if there is little evidence to support its utility for post-exposure
      prophylaxis, doxycycline plus rifampicin is recommended for 3 to 6 weeks.

PMID- 29183472
TI  - Surveillance of Lyme borreliosis in Germany, 2002 and 2003.
AB  - Lyme borreliosis is a potentially serious infection common in Germany, but little
      data about its incidence, distribution, and clinical manifestations are
      available. Lyme borreliosis is not a notifiable disease in Germany, but six of
      Germany's 16 states - Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen,
      Sachsen-Anhalt and Thuringen, have enhanced notification systems, which do
      include Lyme borreliosis. The efforts made in these states to monitor confirmed
      cases through notification are therefore an important contribution to
      understanding the epidemiology of Lyme borreliosis in Germany. This report
      summarises the analysis of Lyme borreliosis cases submitted to the Robert Koch
      Institut during 2002-2003. The average incidence of Lyme borreliosis of the six
      East German states was 17.8 cases per 100 000 population in 2002 and increased by
      31% to 23.3 cases in 2003, respectively. Patient ages were bimodally distributed,
      with incidence peaks among children aged 5- 9 and elderly patients, aged 60- 64
      in 2002, and 65- 69 in 2003. For both years, 55% of patients were female. Around
      86% of notified cases occurred from May to October. Erythema migrans affected
      2697 patients (89.3%) in 2002 and 3442 (86.7%) in 2003. For a vector-borne
      disease, like Lyme borreliosis, the risk of infection depends on the degree and
      duration of contact between humans and ticks harbouring Borrelia burgdorferi. As
      infectious ticks probably occur throughout Germany, it is likely that the
      situation in the remaining 10 German states is similar to that of the states in
      this study.

PMID- 29183473
TI  - Travel Associated Legionnaires' Disease in Europe : 2003.
AB  - Six hundred and thirty two cases of travel-associated legionnaires' disease with
      onset in 2003 were reported to the EWGLINET surveillance scheme by 24 countries.
      Eighty nine clusters were detected, 35 (39%) of which would not have been
      detected without the EWGLINET scheme. One hundred and seven accommodation sites
      were investigated and 22 sites were published on the EWGLI website. The
      proportion of cases diagnosed primarily by the urinary antigen test was 81.2%,
      and 48 positive cultures were obtained. Thirty eight deaths were reported to the
      EWGLINET scheme, giving a crude fatality rate of 6%. Countries are encouraged to
      inform the coordinating centre of cases that fall ill after travelling within
      their own country of residence ('internal travel'), and are also encouraged to
      obtain patient isolates for culture where at all possible.

PMID- 29183474
TI  - Quality assurance for the diagnostics of viral diseases to enhance the emergency
      preparedness in Europe.
AB  - The threat posed by emerging and re-emerging communicable diseases and, more
      recently, by the intentional release of infectious agents in a susceptible
      population, has been receiving considerable attention at the national and
      international levels. Public health efforts to strengthen disease detection,
      surveillance and control have been intensified. However, clinicians and clinical
      microbiology laboratories play an important role in the early detection of
      disease, the identification of the putative agent, and notification of the
      appropriate authorities. To be effective in this role, laboratories must be
      specially prepared to handle viral agents safely, and need, among other things,
      the appropriate rapid and sensitive diagnostic tests. In 1998 the European
      Network for Diagnostics of "Imported" Viral Diseases (ENIVD) was established.
      ENIVD presently comprises, as permanent members, 44 expert laboratories in 21
      European Union (EU) member states and 4 non-EU countries and is one of the
      networks on infectious diseases funded by the European Commission. ENIVD fulfils
      many of the important tasks required for the surveillance and control of
      imported, rare and emerging viral infections such as the exchange of expertise
      and the organisation of external quality assurance (EQA) programmes, both of
      which are needed to improve diagnostics. Here, we summarise the data generated by
      recent EQA activities focussed on the diagnostics of infections with hantavirus,
      dengue virus, filovirus, Lassa virus, orthopox virus and the SARS-coronavirus
      (SARS-CoV). These were carried out between 1999 and 2004 and involved 93
      laboratories from 41 countries, including laboratories from additional countries
      outside of Europe. Particularly the EU-candidate countries and Eastern
      neighbouring countries will be invited to join the network in the near future. A
      public website is available at http://www.enivd.de.

PMID- 29183475
TI  - Bichat guidelines for the clinical management of plague and bioterrorism-related
      plague.
AB  - Yersinia pestis appears to be a good candidate agent for a bioterrorist attack.
      The use of an aerosolised form of this agent could cause an explosive outbreak of
      primary plague pneumonia. The bacteria could be used also to infect the rodent
      population and then spread to humans. Most of the therapeutic guidelines suggest
      using gentamicin or streptomycin as first line therapy with ciprofloxacin as
      optional treatment. Persons who come in contact with patients with pneumonic
      plague should receive antibiotic prophylaxis with doxycycline or ciprofloxacin
      for 7 days. Prevention of human-to-human transmission via patients with plague
      pneumonia can be achieved by implementing standard isolation procedures until at
      least 4 days of antibiotic treatment have been administered. For the other
      clinical types of the disease, patients should be isolated for the first 48 hours
      after the initiation of treatment.

PMID- 29183476
TI  - Varicella zoster virus vaccination policies and surveillance strategies in
      Europe.
AB  - The incorporation of varicella zoster virus (ZVV) vaccination in childhood
      immunisation schedules is becoming an increasingly common option in Europe. The
      current study forms part of the European Sero-Epidemiology Network 2 (ESEN2)
      organisational analysis for VZV and describes current passive immunisation
      policies, as well as current and proposed active immunisation strategies, and
      existing surveillance systems for diseases caused by the varicella zoster virus
      in ESEN countries.

PMID- 29183477
TI  - Bioterrorism, Glanders and melioidosis.
AB  - We note with interest the recently published guidelines for management of
      melioidosis and glanders. We are clinicians with extensive experience with
      melioidosis in Australia and Thailand and would like to express our concern at a
      number of inaccuracies in these guidelines.

PMID- 29183478
TI  - Syphilis surveillance in France, 2000-2003.
AB  - This article describes syphilis trends, characteristics of patients from 2000 to
      2003 in France and trends of the benzylpenicillin benzathine 2.4 million UI sales
      from 2001 to 2003. The ongoing surveillance system for syphilis case reporting
      since 2001 has been set up in volunteer settings, mostly public settings where
      STI treatment is offered. Clinical case reporting is complemented by sexual
      behavioural data based on a self-administered questionnaire. From 2000 to 2003,
      1089 syphilis cases were reported in France, increasing from 37 cases in 2000 to
      428 in 2003. Overall, 96% of syphilis cases were in men with a mean age of 36.5
      years and 70% of whom were born in France. The proportion of syphilis cases with
      HIV co-infection decreased over time from 60% in 2000 to 33% in 2003. The most
      affected area by the syphilis epidemic is the Ile-de-France region, mainly the
      city of Paris. The greatest proportion of syphilis cases diagnosed in men who
      have sex with men (MSM) were in the Ile-de-France region, where they made up 87%
      of cases, compared with 75% in other regions. Among the patients who completed
      the self-administered questionnaire on sexual behaviour, 83% reported having
      casual sex partners in the 3 months prior to their syphilis diagnosis. Trends in
      the sales of benzylpenicillin benzathine 2.4 million UI in private pharmacies are
      similar to those observed in the surveillance system, and increased between 2001
      and 2003. In conclusion, syphilis transmission is still ongoing in France in 2003
      and the role of unprotected oral sex in the transmission of syphilis should be
      emphasised.

PMID- 29183479
TI  - Bichat guidelines for the clinical management of haemorrhagic fever viruses and
      bioterrorism-related haemorrhagic fever viruses.
AB  - Haemorrhagic fever viruses (HFVs) are a diverse group of viruses that cause a
      clinical disease associated with fever and bleeding disorder. HFVs that are
      associated with a potential biological threat are Ebola and Marburg viruses
      (Filoviridae), Lassa fever and New World arenaviruses (Machupo, Junin, Guanarito
      and Sabia viruses) (Arenaviridae), Rift Valley fever (Bunyaviridae) and yellow
      fever, Omsk haemorrhagic fever, and Kyanasur Forest disease (Flaviviridae). In
      terms of biological warfare concerning dengue, Crimean-Congo haemorrhagic fever
      and Hantaviruses, there is not sufficient knowledge to include them as a major
      biological threat. Dengue virus is the only one of these that cannot be
      transmitted via aerosol. Crimean-Congo haemorrhagic fever and the agents of
      haemorrhagic fever with renal syndrome appear difficult to weaponise. Ribavirin
      is recommended for the treatment and the prophylaxis of the arenaviruses and the
      bunyaviruses, but is not effective for the other families. All patients must be
      isolated and receive intensive supportive therapy.

PMID- 29183480
TI  - An outbreak of Campylobacter jejuni enteritis in a school of Madrid, Spain.
AB  - An outbreak of gastroenteritis caused by Campylobacter infection was identified
      in May 2003 in a school in Madrid, Spain. Eighty one cases were identified in a
      total of 253 people studied. A retrospective cohort study showed that a custard
      made with ultra high temperature (UHT) milk was associated with illness (RR:
      3.15; 95% CI: 1.25-7.93). The custard was probably contaminated with
      Campylobacter jejuni from a raw chicken prepared a day previously in the same
      kitchen. Our recommendations were to periodically remind the school's authorities
      how to act if an outbreak should be suspected, to include the monitoring of a
      food handler's working day in each environmental investigation in order to detect
      any risk behaviour; to implement microbiological analysis from the surfaces and
      utensils of the collective kitchens and improve the sanitary education of food
      handlers.

PMID- 29183481
TI  - Mandatory disease reporting by German laboratories: a survey of attitudes,
      practices and needs.
AB  - In 2000, the new German infectious disease control act replaced aggregate with
      individual case reporting. The process was facilitated by the simultaneous
      introduction of electronic data transfer within the public health system.
      Reporting laboratories have not been electronically connected to this network. A
      survey by means of a postal questionnaire was conducted in 2003 among 537 German
      medical microbiology laboratories to explore their reporting habits, preference
      for electronic reporting formats, and relevant software equipment. Almost 90% of
      the respondents indicated a reporting delay of no more than 24 hours and 45% were
      still manually filling in paper forms for reporting purposes. The introduction of
      electronic reporting formats was favoured by 74% of the laboratories although 33%
      were not using any microbiology-specific software and the remaining 67% listed 62
      different products. Pilot projects with selected software manufacturers might
      help to pave the way for the implementation of a standardised electronic
      infectious disease reporting format in Germany.

PMID- 29183483
TI  - Science news.

PMID- 29183482
TI  - Measles outbreak in the Provence - Alpes - Cote d'Azur region, France, January -
      July 2003.
AB  - At the end of May 2003, the Marseilles Hospital Centre's virology laboratory
      informed the French public heath institute of 5 cases of confirmed measles among
      young adults living in Marseilles. An investigation was conducted, consulting
      different community and hospital health services, to determine the virus
      circulation in the Provence-Alpes-Cote d'Azur (PACA) region by the southern
      interregional epidemiological cell. The investigation identified 259 cases: 183
      clinical, 74 serologically confirmed and 2 epidemiologically linked cases. The
      first cases were identified during the first six months of 2003, with a peak in
      April. This outbreak of measles in the PACA region was favoured by poor
      vaccination coverage, which created groups of susceptible population. The real
      number of cases was probably higher than the number identified. This
      investigation has outlined the limitations of the measles surveillance system in
      France: the sentinel network had not detected any case for this period. France
      needs to reach the WHO objective of measles elimination by 2010 and the
      surveillance tools used must be those already used in the most countries that are
      furthest advanced in the elimination process. To reach this goal, the Direction
      Generale de la Sante has nominated a working group to be in charge of proposing a
      national plan to interrupt indigenous measles transmission in France.

PMID- 29183484
TI  - Bichat guidelines for the clinical management of smallpox and bioterrorism
      related smallpox.
AB  - Smallpox is a viral infection caused by the variola virus. It was declared
      eradicated worldwide by the Word Health Organization in 1980 following a smallpox
      eradication campaign. Smallpox is seen as one of the viruses most likely to be
      used as a biological weapon. The variola virus exists legitimately in only two
      laboratories in the world. Any new case of smallpox would have to be the result
      of human accidental or deliberate release. The aerosol infectivity, high
      mortality, and stability of the variola virus make it a potential and dangerous
      threat in biological warfare. Early detection and diagnosis are important to
      limit the spread of the disease. Patients with smallpox must be isolated and
      managed, if possible, in a negative-pressure room until death or until all scabs
      have been shed. There is no established antiviral treatment for smallpox. The
      most effective prevention is vaccination before exposure.

PMID- 29183485
TI  - Bichat guidelines for the clinical management of tularaemia and bioterrorism
      related tularaemia.
AB  - Francisella tularensis is one of the most infectious pathogenic bacteria known,
      requiring inoculation or inhalation of as few as 10 organisms to initiate human
      infection. Inhalational tularaemia following intentional release of a virulent
      strain of F. tularensis would have great impact and cause high morbidity and
      mortality. Another route of contamination in a deliberate release could be
      contamination of water. Seven clinical forms, according to route of inoculation
      (skin, mucous membranes, gastrointestinal tract, eyes, respiratory tract), dose
      of the inoculum and virulence of the organism (types A or B) are identified. The
      pneumonic form of the disease is the most likely form of the disease should this
      bacterium be used as a bioterrorism agent. Streptomycin and gentamicin are
      currently considered the treatment of choice for tularemia. Quinolone is an
      effective alternative drug. No isolation measures for patients with pneumonia are
      necessary. Streptomycin, gentamicin, doxycycline or ciprofloxacin are recommended
      for post-exposure prophylaxis.

PMID- 29183486
TI  - Epidemiological and virological assessment of influenza activity in Europe during
      the 2003-2004 season.
AB  - The 2003-2004 influenza season in Europe was dominated by the spread of the new
      drift variant A/Fujian/411/2002 (H3N2)-like virus which was not perfectly matched
      with the A(H3N2) component of the influenza vaccine. Sporadic cases of this virus
      were detected in Europe at the end of the 2002-2003 season and influenza activity
      associated with this virus began relatively early during the 2003-2004 season.
      Generally, influenza activity first occurred in the west of Europe (Ireland, the
      United Kingdom and the Iberian Peninsula) in October/November and gradually moved
      east across Europe, affecting Latvia, Lithuania and Poland during the months of
      January and February 2004. In general, the intensity of clinical activity was
      higher than during the 2002-2003 season (in 13 out of 20 networks) and, in
      countries reporting age specific data, the highest consultation incidences were
      observed among children aged 0-14. However, despite the emergence of the A(H3N2)
      drift variant, clinical incidences were not especially high compared with
      historical data. The composition of the 2004-2005 influenza vaccine has been
      modified compared with the 2003-2004 season and includes an A/Fujian/411/2002
      (H3N2)-like virus strain and a new B virus strain (a B/Shanghai/361/2002-like
      virus).

PMID- 29183487
TI  - Bichat guidelines for the clinical management of botulism and bioterrorism
      related botulism.
AB  - Botulism is a rare but serious paralytic illness caused by botulinum toxin, which
      is produced by the Clostridium botulinum. This toxin is the most poisonous
      substance known. It 100 000 times more toxic than sarin gas. Eating or breathing
      this toxin causes illness in humans. Four distinct clinical forms are described:
      foodborne, wound, infant and intestinal botulism. The fifth form, inhalational
      botulism, is caused by aerosolised botulinum toxin that could be used as a
      biological weapon. A deliberate release may also involve contamination of food or
      water supplies with toxin or C. botulinum bacteria. By inhalation, the dose that
      would kill 50% of exposed persons (LD50) is 0.003 microgrammes/kg of body weight.
      Patients with respiratory failure must be admitted to an intensive care unit and
      require long-term mechanical ventilation. Trivalent equine antitoxins (A,B,E)
      must be given to patients as soon as possible after clinical diagnosis.
      Heptavalent human antitoxins (A-G) are available in certain countries.

PMID- 29183488
TI  - Impact of the meningococcal C conjugate vaccine in Spain: an epidemiological and
      microbiological decision.
AB  - The new meningococcal C conjugate vaccine became available in Spain and was
      included in the infant vaccination schedule in 2000. A catch-up campaign was
      carried out in children under six years of age. As a consequence, the incidence
      of meningococcal disease caused by serogroup C has fallen sharply during the last
      three epidemiological years in Spain. The risk of contracting serogroup C disease
      in 2002/2003 fell by 58% when compared with the season before the conjugate
      vaccine was introduced. There was also an important decrease in mortality. Three
      deaths due to serogroup C occurred in the age groups targeted for vaccination in
      2002/2003, compared with 30 deaths in the same age groups in the season before
      the launch of the vaccine campaign. In the catch-up campaign the vaccine coverage
      reached values above 92%. For the 2001, 2002 and 2003 routine childhood
      immunisation programme coverage values ranged from 90% to 95%. During the past
      three years a total of 111 cases of serogroup C disease have been reported in
      patients in the vaccine target group. Most of the vaccination failures occurred
      during the epidemiological year 2002/2003. Eight (53%) vaccine failures occurred
      in children who had been routinely immunised in infancy, and could be related to
      a lost of protection with time since vaccination. The isolation of several
      B:2a:P1.5 strains (ST-11 lineage) is noteworthy. These may have their origin in
      C:2a:P1.5 strains which, after undergoing genetic recombination at the capsular
      operon level, express serogroup B. These strains could have relevant epidemic
      potential.

PMID- 29183489
TI  - Suspected SARS patients hospitalised in French isolation units during the early
      SARS epidemic: The French experience.
AB  - During the SARS epidemic, many patients were screened according to WHO criteria
      but never went on to develop SARS. In May 2003, early in the epidemic, we
      conducted a retrospective study to describe suspected SARS patients hospitalised
      in France and compared them with documented cases of patients with SARS to
      evaluate the screening strategy. A total of 117 patients were studied. Only 3.4%
      had been in close contact with a SARS patient but 73.5% came from an affected
      area. 67.5% had fever and respiratory symptoms on their admission to hospital.
      49.6% had fever and non specific symptoms. Clinical symptoms that were
      significantly more common among patients with SARS were fever, myalgia, dyspnoea,
      and nausea or vomiting. Presumed viral fever and respiratory tract infection were
      the most common diagnosis. Symptoms cannot be distinguished from an early stage
      of SARS confirming the usefulness of the WHO case definitions in isolation
      decision to avoid further transmission.

PMID- 29183490
TI  - Rubella in Denmark.
AB  - An average of 20 000 rubella cases were recorded annually in Denmark until 1987.
      In 1989, however, only 1006 cases were reported, and the true current incidence
      of rubella infection in Denmark is unknown but considered to be very low and <1
      per 100 000 population. The significant decrease in the inci-dence of rubella
      mirrors the success of vaccination of rubella seronegative women of childbearing
      age, which was initiated in Denmark in 1980. From 1982 and onwards the national
      health security scheme also refunded vaccina-tion of children and the MMR vaccine
      was introduced in the Danish child-hood vaccination program in 1987. The low
      incidence has been sustainable due to these interventions, and since 1994
      congenital rubella syndrome and rubella in pregnancy have been listed as
      notifiable infectious diseases in Denmark. Nevertheless, in order to meet the WHO
      goal of control of rubella in the Region, the introduction of mandatory reporting
      of all laboratory diagnosed rubella cases is now being considered.

PMID- 29183491
TI  - Basic Surveillance Network, a European database for surveillance data on
      infectious diseases.
AB  - The Basic Surveillance Network was started in 2000 and is one of the networks on
      infectious diseases funded by the European Commission. The network collects and
      makes readily available basic surveillance data on infectious diseases from all
      the 'old' (pre-2004) European Union member states. The aim is to provide easy
      access to descriptive data that already exist in national databases, so that it
      is possible to monitor and compare incidence trends for infectious diseases in
      the EU member states. The list of diseases covered by the network has recently
      been expanded from 10 initial 'pilot' diseases to over 40 diseases listed by the
      EU to be under surveillance. In the near future, the new member states will be
      invited to participate in the network. Data are case-based and comprise date of
      onset of disease, age and sex. Only a very short list of disease specific
      additional variables, such as country of infection or immunisation status, is
      collected. Classification of cases ( possible, probable, confirmed) is specified
      according to EU case definitions. The participants of the network have access to
      an internal web site were all the data is presented in tables and graphs. An open
      website is available for the public at https://www.eubsn.org./BSN/.

PMID- 29183492
TI  - Residual risk of transfusion-transmitted viral infections in Spain, 1997-2002,
      and impact of nucleic acid testing.
AB  - Estimates of the risk of bloodborne viral infections are essential for monitoring
      the safety of the blood supply and the impact of new screening tests. Incidence
      rates of seroconversion and the residual risk for HBV, HIV and HCV were
      calculated among Spanish repeat donors between 1997 and 1999 at 22 blood donation
      centres, and at 7 centres between 2000 and 2002. The residual risk per million
      donations was estimated to be 18.67 for HBV, 2.49 for HIV and 10.96 for HCV
      (between 1997 and 1999). For the 2000-2002 period, the residual risk per million
      donations was estimated to be 9.78 for HBV, 2.48 for HIV and 3.94 for HCV.
      Between 1999 and 2003, about 3.4 million donations were tested by NAT, mainly in
      pools of 44 donations, in 12 of the 22 Spanish blood donation centres
      participating in the study. Eight anti-HCV negative and HCV-RNA positive
      donations were found, which represent an approximate yield of 1/420 000, versus a
      projected yield of 1/240 000 obtained from 1995-1997 data. The residual risks of
      transfusion-transmitted viral infections in Spain were low, and with the
      implementation of NAT these risks are even lower.

PMID- 29183493
TI  - Bichat clinical guidelines for bioterrorist agents.
AB  - The deliberate release of anthrax in the United States shortly after the
      terrorist attacks of 11 September 2001 brought about a radical change in people's
      perception of the risk of bioterrorism. These bioterrorist events, unlike others
      before, had a worldwide impact not only in respect of security and public health
      but also in other sectors. Governments and international entities with
      responsibilities related to maintenance of peace, security, safety and health
      protection reviewed urgently their political, economic, diplomatic, military and
      legal means to face up to such attacks and embarked upon major efforts to
      increase their preparedness.

PMID- 29183494
TI  - Recent syphilis trends in Belgium and enhancement of STI surveillance systems.
AB  - Over the past five years, a series of syphilis outbreaks mainly occurring among
      gay men have been observed in Europe. One of these outbreaks was reported in the
      city of Antwerp, Belgium, during the first quarter of 2001. This outbreak is
      still ongoing in 2004. Furthermore, active syphilis diagnoses reported by the
      Sentinel Laboratory Network rose by 89% in the country during the fourth quarter
      of 2003. An increase in Brussels was also observed during the same quarter
      (+300%; 24 cases reported). Overall, the sentinel network of clinicians reported
      that 93.4% of patients were male; among them, 79.9% were men having sex with men
      (MSM). The overall proportion of patients co-infected with HIV was 50.5% (MSM:
      58.6%; male heterosexuals: 23.8%; females: 8.3%); 76.1% of co-infected patients
      were already aware of their HIV infection at the time they were diagnosed with
      syphilis.

PMID- 29183495
TI  - Hepatitis A outbreak among MSM linked to casual sex and gay saunas in Copenhagen,
      Denmark.
AB  - During an outbreak of hepatitis A predominantly among men who have sex with men
      (MSM) in Copenhagen, Denmark, in 2004, we did a case-control study to determine
      risk factors for infection. A case was an MSM >17 years, living in Copenhagen,
      with IgM positive hepatitis A infection diagnosed between June and August 2004,
      and without a household contact with a hepatitis A case before onset of illness.
      Controls were selected at the Copenhagen Pride Festival. The study included 18
      cases and 64 controls. Sixteen of 18 cases and 36/63 controls had sex with casual
      partners (ORMH 5.6, 95% CI 1.2-26.9). Eleven of 18 cases and 14/62 controls had
      sex in gay saunas (ORMH 4.2, 95% CI 1.5-11.5). Sex at private homes appeared to
      be protective (ORMH 0.2, 95% CI 0.1-0.7). Casual sex including sex in gay saunas
      was an important risk factor for the spread of HAV among MSM in Copenhagen. The
      results are in accordance with findings in other European outbreaks. As the
      general immunity to hepatitis A decreases and the outbreak potential increases,
      we recommend health education and hepatitis A vaccination to all MSM not living
      in monogamous relationships, especially if they visit gay saunas or other places
      with frequent partner change. To stop spread of hepatitis A among MSM in Europe,
      a European consensus on prevention and control measures may be required.

PMID- 29183496
TI  - Impact of nucleic acid amplification technology (NAT) in Italy in the three years
      following implementation (2001-2003).
AB  - The use of NAT technology to screen blood donations in Italy became mandatory on
      28 June 2002, but had been available experimentally since 2001. During the
      transition period, an EIA test to detect hepatitis C core antigen (HCVcoreAg) had
      also been permitted. Considering the large number of blood transfusion centres in
      Italy, an initial reorganisation of the biological validation of blood units was
      necessary, with a partial centralisation of NAT testing. The Gruppo Italiano per
      lo Studio delle Malattie Trasmissibili con la Trasfusione (Italian Group for the
      Study of Transfusion-Transmissible Diseases) conducted a national survey
      evaluating NAT testing, based on an annual collection of data through a
      questionnaire sent to all centres. In the first three years of the investigation,
      219 blood transfusion centres returned the questionnaires. In the period between
      January 2001 and December 2003, 3 894 894 blood donations were investigated for
      HCV RNA and 2 186 468 for HIV RNA. Of these, 12 were found to be HCV RNA positive
      and four HIV RNA positive, with an observed NAT versus antibody-based assay yield
      of 3.1/106 donations for HCV and 1.8/106 donations for HIV, respectively. Five of
      the 12 HCV RNA positive and anti-HCV negative donors had abnormal ALT values and
      their donations would have been discarded even in absence of NAT testing. Thus
      the final NAT yield for HCV is 1.79/106. The residual risk for HCV or HIV
      transmission by blood transfusion after NAT implementation is currently estimated
      to be extremely low in Italy.

PMID- 29183497
TI  - Interruption of measles transmission in Gipuzkoa (Basque Country), Spain.
AB  - Measles vaccine was introduced in Gipuzkoa (Basque country, Spain) in 1978 and
      was replaced by the measles, mumps, and rubella (MMR) vaccine for children aged
      12-15 months in 1981. A second dose of the MMR vaccine was introduced in 1992.
      Both doses of the MMR vaccine were well accepted by the population and high
      coverage was achieved (95% and 91% for the first and second doses respectively
      for the period 1993-2002). Measles virus circulation was interrupted in the
      second half of the 1990s: no cases of indigenous measles were notified between
      1998 and 2003, and only imported cases have been confirmed during this period.
      These data indicate that the measles vaccination programme implemented has been
      effective. Nevertheless, to avoid measles outbreaks following viral introduction,
      high MMR vaccine coverage levels for the two doses have to be maintained (>95%).

PMID- 29183498
TI  - Current situation of human diphyllobothriasis in Europe.
AB  - Diphyllobothriasis, a parasitosis caused by the flatworm Diphyllobothrium latum,
      is contracted by consuming raw or undercooked freshwater fish. The aim of this
      study was to evaluate the situation of this parasitosis during the past 20 years
      in Europe through the analysis of databases and search engines (Medline, Cabi
      Helminthological abstracts,Yahoo, Google), and through a questionnaire sent to a
      network of European parasitologists and to microbiological laboratories located
      on the shores of the large Alpine lakes. This study has shown that several dozen
      cases have been reported each year in Finland and Sweden, that there have been
      numerous cases in the French or Italian speaking areas of subalpine lakes, and
      that sporadic cases only have been observed in Austria, Spain, Greece, Romania,
      Poland and Norway. Over 30 cases have been identified on the Swiss shores of Lake
      Maggiore since 1990, and 70 cases on the Swiss and French shores of Lake Leman
      between 1993 and 2002. Eight to 12% of perch fillets from Lake Leman and 7.8 % of
      perch from Lake Maggiore were infested with larvae. Contamination sources include
      marinated fish fillets in northern Europe, 'carpaccio di persico' in northern
      Italy, and perch and charr consumed raw or undercooked around Lake Leman. Factors
      allowing the continuation of the parasitic cycle include the continued dumping of
      wastewater into lakes, yachtsmen who also fish, and a possible animal reservoir.

PMID- 29183499
TI  - Bichat guidelines for the clinical management of anthrax and bioterrorism-related
      anthrax.
AB  - The spore-forming Bacillus anthracis must be considered as one of the most
      serious potential biological weapons. The recent cases of anthrax caused by a
      deliberate release reported in 2001 in the United States point to the necessity
      of early recognition of this disease. Infection in humans most often involves the
      skin, and more rarely the lungs and the gastrointestinal tract. Inhalational
      anthrax is of particular interest for possible deliberate release: it is a life
      threatening disease and early diagnosis and treatment can significantly decrease
      the mortality rate. Treatment consists of massive doses of antibiotics and
      supportive care. Isolation is not necessary. Antibiotics such as ciprofloxacin
      are recommended for post-exposure prophylaxis during 60 days.

PMID- 29183500
TI  - Outbreaks caused by parvovirus B19 in three Portuguese schools.
AB  - This paper reports the study of outbreaks of an acute exanthematous disease among
      children of three schools in the municipality of Braga (Portugal). Laboratory
      tests were performed for five cases, showing that the disease was not due to
      infection by measles or rubella virus, and infection with parvovirus B19 was
      confirmed. There were 41 cases in children: 12 in the kindergarten, 17 in the
      secondary school and 12 in the primary school. There was only one case in a staff
      member, who worked in the kindergarten. Eight cases were identified among
      household contacts; two of them were brothers, one from the kindergarten and
      another from the secondary school, where the outbreak occurred after the
      kindergarten outbreak. The estimated values of the basic reproduction number R0
      were very low and it is very likely that asymptomatic infectious cases have
      occurred. The local health authority produced written documents and met with
      staff members and parents. Primary healthcare facilities and the obstetric
      department of the local hospital were also informed. As we are approaching the
      elimination of measles in Portugal and the rest of Europe, with very high vaccine
      coverage, it is very likely that a high proportion of infectious non-vesicular
      exanthemas will be due to B19 infections. This is to be taken into account in the
      design and conduct of surveillance activities, in the context of measles and
      rubella elimination programmes.

PMID- 29183519
TI  - Abdominal Trauma Revisited.
AB  - Although abdominal trauma has been described since antiquity, formal laparotomies
      for trauma were not performed until the 1800s. Even with the introduction of
      general anesthesia in the United States during the years 1842 to 1846,
      laparotomies for abdominal trauma were not performed during the Civil War. The
      first laparotomy for an abdominal gunshot wound in the United States was finally
      performed in New York City in 1884. An aggressive operative approach to all forms
      of abdominal trauma till the establishment of formal trauma centers (where data
      were analyzed) resulted in extraordinarily high rates of nontherapeutic
      laparotomies from the 1880s to the 1960s. More selective operative approaches to
      patients with abdominal stab wounds (1960s), blunt trauma (1970s), and gunshot
      wounds (1990s) were then developed. Current adjuncts to the diagnosis of
      abdominal trauma when serial physical examinations are unreliable include the
      following: 1) diagnostic peritoneal tap/lavage, 2) surgeon-performed ultrasound
      examination; 3) contrast-enhanced CT of the abdomen and pelvis; and 4) diagnostic
      laparoscopy. Operative techniques for injuries to the liver, spleen, duodenum,
      and pancreas have been refined considerably since World War II. These need to be
      emphasized repeatedly in an era when fewer patients undergo laparotomy for
      abdominal trauma. Finally, abdominal trauma damage control is a valuable
      operative approach in patients with physiologic exhaustion and multiple injuries.

PMID- 29183520
TI  - The Effect of Sarcopenia on Outcomes in Geriatric Blunt Trauma.
AB  - Elderly patients are at a higher risk of morbidity and mortality after trauma,
      which is reflected through higher frailty indices. Data collection using existing
      frailty indices is often not possible because of brain injury, dementia, or
      inability to communicate with the patient. Sarcopenia is a reliable objective
      measure for frailty that can be readily assessed in CT imaging. In this study, we
      aimed to evaluate the effect of sarcopenia on the outcomes of geriatric blunt
      trauma patients. Left psoas area (LPA) was measured at the level of the third
      lumbar vertebra on the axial CT images. LPA was normalized for height (LPA
      mm2/m2) and after stratification by gender, sarcopenia was defined as LPA
      measurements in the lowest quartile. A total of 1175 patients consisting of 597
      males and 578 females were studied. LPAs below 242.6 mm2/m2 in males and below
      187.8 mm2/m2 in females were considered to be sarcopenic. We found sarcopenia in
      149 males and 145 females. In multivariate analysis, sarcopenia was associated
      with a higher risk of in-hospital mortality (odds ratio [OR]: 1.61, 95%
      confidence interval [CI]: 1.01-2.56) and a higher risk of discharge to less
      favorable destinations (OR: 1.42, 95% CI: 1.05-1.97). Lastly, sarcopenic patients
      had an increased risk of prolonged hospitalization (hazard ratio: 1.21, 95% CI:
      1.04-1.40).

PMID- 29183521
TI  - Utility of Laparoscopic Subtotal Cholecystectomy with or without Cystic Duct
      Ligation for Severe Cholecystitis.
AB  - We use open cholecystectomy (OC) to treat severe cholecystitis in cases in which
      we are worried that inflammation might cause anatomical changes in Calot's
      triangle. Furthermore, in cases of severe cholecystitis in which marked
      inflammation leads to fibrosis, we perform subtotal cholecystectomy (SC), i.e.,
      incomplete gallbladder resection. Laparoscopic SC (LSC) without cystic duct
      dissection is considered to be effective at reducing the incidence of serious
      complications in patients with severe cholecystitis. The cases of 246 patients
      who underwent cholecystectomy for benign gallbladder disease between January 2011
      and May 2015 were evaluated retrospectively. Of these patients, 14 were treated
      with LSC, and 19 underwent OC. Moreover, three patients in the LSC group
      underwent LSC without cystic duct ligation because it was considered that it
      would be difficult to dissect and ligate the cystic duct. The LSC group suffered
      significantly less intraoperative blood loss than the OC group. However, the
      operative times of the two groups were similar. Moreover, the duration of the
      postoperative hospitalization period was significantly shorter in the LSC group
      than in the OC group. Next, we compared the long-term outcomes of the SC and
      total cholecystectomy groups, regardless of the surgical method. No cases of
      cholecystitis or gallbladder cancer were encountered in either group. It is
      suggested that LSC is safe, effective, and helps to prevent serious complications
      in cases of severe cholecystitis that require conversion to OC, regardless of
      whether cystic duct ligation is performed.

PMID- 29183523
TI  - Hypoalbuminemia and Clinical Outcomes: What is the Mechanism behind the
      Relationship?
AB  - Albumin has a number of important physiologic functions, which include
      maintaining oncotic pressure, transporting various agents (fatty acids, bile
      acids, cholesterol, metal ions, and drugs), scavenging free oxygen radicals,
      acting as an antioxidant, and exerting an antiplatelet effect. Hypoalbuminemia in
      adults, defined by an intravascular albumin level of <3.5 g/dL, is associated
      with poor postoperative outcomes in patients undergoing surgical intervention.
      Although the relationship of hypoalbuminemia and poor surgical outcome has been
      known for many years, the pathophysiology behind the relationship is unclear.
      Three theoretical constructs might explain this relationship. First, albumin
      might serve as a nutritional marker, such that hypoalbuminemia represents poor
      nutritional status in patients who go on to experience poor postoperative
      outcomes. Second, albumin has its own pharmacologic characteristics as an
      antioxidant or transporter, and therefore, the lack of albumin might result in a
      deficiency of those functions, resulting in poor postoperative outcomes. Or
      third, albumin is known to be a negative acute phase protein, and as such
      hypoalbuminemia might represent an increased inflammatory status of the patient,
      potentially leading to poor outcomes. A thorough review of the literature reveals
      the fallacy of these arguments and fails to show a direct cause and effect
      between low albumin levels per se and adverse outcomes. Interventions designed
      solely to correct preoperative hypoalbuminemia, in particular intravenous albumin
      infusion, do little to change the patient's course of hospitalization. While
      surgeons may use albumin levels on admission for their prognostic value, they
      should avoid therapeutic strategies whose main endpoint is correction of this
      abnormality.

PMID- 29183522
TI  - Peripheral Nerve Injury during Abdominal-Pelvic Surgery: Analysis of the National
      Surgical Quality Improvement Program Database.
AB  - Peripheral nerve injury (PNI) is a rare but preventable complication of surgery.
      We sought to assess whether the use of minimally invasive surgery (MIS) affects
      the occurrence of PNI. Using the American College of Surgeons National Surgical
      Quality Improvement Program database, we examined rates of PNI among patients
      undergoing appendectomy, hysterectomy, colectomy, or radical prostatectomy
      between 2005 and 2012. We assessed the effect of MIS, as compared with open
      surgery, on PNI occurrence using logistic regression. Among 297,532 patients, of
      whom 175,884 (59.1%) underwent MIS, the rate of PNI was 0.03 per cent. Forty-four
      patients treated using MIS had PNI (0.03%) as compared with 63 who underwent open
      surgery (0.05%; P = 0.0002). There was a significant decrease in the proportion
      of surgeries resulting in PNI (P < 0.0001) over time. In univariate analysis, MIS
      was associated with a decreased occurrence of PNI (odds ratio 0.48, 95%
      confidence interval 0.33-0.71), but this became nonsignificant on multivariable
      analysis (odds ratio 0.71, 95% confidence interval 0.47-1.09). Increased
      operative time and smoking status were the only factors independently associated
      with an increased risk of PNI on multivariable analysis. MIS techniques during
      common abdominal-pelvic surgeries do not appear to increase the risk of PNI.
      Prolonged operative time and smoking are independently associated with an
      increased risk of PNI. Quality improvement initiatives to increase awareness of
      PNI and identify patients at increased risk of this preventable complication
      should be considered.

PMID- 29183524
TI  - The Place of Elastography in Evaluating the Efficacy of Radiofrequency Ablation
      of Thyroid Nodules.
AB  - The usage of radiofrequency ablation (RFA) therapy and elastography to treat
      thyroid nodules has been increasing recently. Elastography specifically measures
      the stiffness of tissue using ultrasonography (US). The aim of the present study
      was to evaluate the relationship between the elastography values of thyroid
      nodules and the efficacy of RFA therapy. Ultrasonography was performed on 49
      patients who had a thyroid nodule with a diameter of 1 cm or greater before RFA
      therapy. The RFA was performed under local anesthesia, and elastography was used
      to measure the stiffness of the normal thyroid tissue, sternocleidomastoid muscle
      (SCM) and thyroid nodules three months after RFA. The nodule diameter
      significantly decreased three months after RFA (P < 0.05). According to a cross
      evaluation of the mean elastography rates, the thyroid/SCM and nodule/thyroid
      elastography rates had an inverse relationship (P: 0.009). However, the
      thyroid/SCM elastography rates and nodule/SCM elastography rates (P: 0.022) and
      the thyroid/SCM elastography rates and the rates of reduction (%) of the nodule
      diameter before and three months after RFA (P: 0.016) had positive relationships.
      In conclusion, RFA therapy is more effective in patients with thyroid nodules if
      there are high thyroid tissue/SCM rates in elastography.

PMID- 29183525
TI  - Varying Presentations and Outcomes of Septic Shock: Should Septic Shock Be
      Stratified?
AB  - Recent studies have revealed there are three presentations of septic shock in
      patients: refractory hypotension without hyperlactatemia, hyperlactatemia without
      refractory hypotension, and both refractory hypotension and hyperlactatemia. In
      this study, we sought to identify differences in the outcomes of septic shock
      patients with these three presentations. We performed a secondary analysis of a
      large-scale, multicenter, controlled trial. The septic shock patients were
      categorized into the following three groups according to the presence or absence
      of refractory hypotension and hyperlactatemia: a hypotension group (refractory
      hypotension without hyperlactatemia), a hyperlactatemia group (hyperlactatemia
      without refractory hypotension), and a typical group (both refractory hypotension
      and hyperlactatemia). The 90-day all-cause mortality was compared among these
      three groups. A total of 1588 septic shock patients were enrolled in the present
      study, including 854 (53.8%) in the hypotension group, 477 (30.0%) in the
      hyperlactatemia group, and 257 (16.2%) in the typical group. The 90-day all-cause
      mortality were 12.3 per cent for the patients in the hypotension group, 23.1 per
      cent for those in the hyperlactatemia group, and 31.9 per cent for those in the
      typical group, these differences among the three groups were significant
      (Pearson's chi2 = 58.49, P < 0.001). And also, there was a significant difference
      between hyperlactatemia group and typical group (Pearson's chi2 = 6.77, P <
      0.05). In this study, we demonstrated that the three different presentations of
      septic shock resulted in significantly different outcomes, suggesting that septic
      shock should be stratified.

PMID- 29183526
TI  - Do Transferred Patients Increase the Risk of Venous Thromboembolism in Trauma
      Centers?
AB  - Trauma patients often require initial stabilization followed by transfer for
      ongoing trauma care. Thus, the administration of VTE prophylaxis is often delayed
      until admission to the receiving hospital. It is unclear if transfer status is a
      risk factor for VTE. The National Trauma Database v6.2 was used to identify
      patients admitted to Level I and II trauma centers. Exclusions included patients
      on anticoagulation, <18 years, known VTE before trauma, or pregnant. Patients
      transferred were compared with nontransferred patients. Analysis included 736,374
      patients with 189,166 (25.69%) transferred patients within 24 hours of injury.
      Using weighted measures, VTE was identified in 11,619 (1.50%) patients. The VTE
      rate was significantly higher in the transferred group compared with the
      nontransferred group (1.73% vs 1.42%, P = 0.002) including deep venous thrombosis
      (1.39% vs 1.14%, P = 0.004) and pulmonary embolism (0.45% vs 0.39%, P = 0.003).
      Multivariable analyses adjusting for patient-level risk factors demonstrated that
      transfer was associated with a higher likelihood of VTE (aOR 1.18; 95% CI: 1.09
      1.28, P <= 0.001), pulmonary embolism (aOR 1.21; 95% CI: 1.11-1.33, P <= 0.001),
      and deep venous thrombosis (aOR 1.17; 95% CI: 1.07-1.28, P = 0.0004). Transfer
      status of trauma patients is a risk factor for VTE. Accepting a transferred
      patient results in an increased VTE risk and may not be reflective of the quality
      of care at the receiving facility.

PMID- 29183527
TI  - Surgical Outcomes in Hepatitis C Virus-Related Hepatocellular Carcinoma: Special
      Reference to Sustained Virological Responses to Interferon Therapy.
AB  - Long-term surgical outcomes after hepatic resection for hepatitis C virus (HCV)
      related hepatocellular carcinoma (HCC) in patients who achieved a sustained
      virological response (SVR) to interferon (IFN) therapy remain inconclusive.
      Clinical records of 277 patients who underwent hepatic resection for HCV-related
      early stage HCC (met the Milan criteria) between 1993 and 2012 were
      retrospectively reviewed. Thirty-seven patients achieved the SVR during HCC
      detection (pre-SVR group), whereas 23 achieved SVR using adjuvant interferon
      therapy after hepatic resection (post-SVR group). The control group included
      remaining 217 patients. We investigated the SVR effects on surgical outcomes.
      Disease-free survival (DFS) rates at 5/10/15 years after hepatic resection were
      significantly greater in the pre and post-SVR groups than in the control group
      (46/30/30per cent and 61/36/27 per cent vs 23/7/7 per cent, respectively; P <
      0.001). Overall survival (OS) rates at 10/15 years after hepatic resection were
      better in the pre- and post-SVR groups than in the control group (68/68 percent
      and 78/78 per cent vs 13/11 per cent, respectively; P < 0.001). On multivariate
      analysis, pre- and post-SVR were independent factors for no recurrence (pre-SVR:
      hazard ratio (HR), 0.48, P = 0.002; post-SVR: HR, 0.41, P = 0.001) and improved
      survival (pre-SVR: HR, 0.36, P = 0.002; post-SVR: HR, 0.122, P < 0.001).
      Achievement of SVR in patients with HCV-related HCC was associated with long-term
      disease-free survival and OS after hepatic resection.

PMID- 29183528
TI  - Conditional Survival-Based "Abbreviated" Routine Cancer Surveillance for
      Pathologic Stage IB Melanoma.
AB  - A negative sentinel lymph node biopsy (SLNB) for stage IB (T1b/T2a N0) melanoma
      would predict an excellent long-term prognosis. Combined with the concept of
      conditional survival, an "abbreviated" cancer surveillance strategy was
      implemented to reduce the number of visits and total length of follow-up.
      Retrospective review of all pathologic stage IB melanoma patients (negative SLNB)
      at a single institution between 2006 and 2008 after implementation of an
      "abbreviated" cancer surveillance; clinic visits every six months for five years
      followed by one annual visit (total follow-up six years). Patient demographics,
      tumor characteristics, and information regarding recurrences were obtained.
      Recurrence-free, disease-specific, and overall survival were calculated. Eighty
      seven patients underwent the "abbreviated" cancer surveillance. Median age was
      55.4 years and 50.6 per cent were male. Median Breslow thickness was 1.1 mm
      (range 0.5-2.0 mm) and 1.1 per cent were ulcerated. Primary tumor site was 49 per
      cent extremities, 39 per cent trunk, and 12 per cent head/neck. Median follow-up
      was 68.6 months. Five-year recurrence-free, disease-specific, and overall
      survivals were 89, 95, and 88 per cent, respectively. During surveillance, 10
      patients had concerning symptoms or physical findings prompting subsequent
      workup, all of which were negative for recurrence/metastases. There were only
      three true melanoma recurrences; all were distant metastases and presented
      symptomatically between scheduled follow-up visits. In light of the excellent
      prognosis for pathologic (SLNB negative) stage IB melanoma, an "abbreviated"
      cancer surveillance schedule based on conditional survival would reduce both
      direct and indirect costs in this cohort. The few recurrences were symptomatic
      and unlikely to have changed with more intensive surveillance.

PMID- 29183529
TI  - Efficiency and Safety of One-Step Procedure Combined Laparoscopic Cholecystectomy
      and Eretrograde Cholangiopancreatography for Treatment of Cholecysto
      Choledocholithiasis: A Randomized Controlled Trial.
AB  - We aimed to evaluate the efficiency and safety of one-step procedure combined
      endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic
      cholecystectomy (LC) for treatment of patients with cholecysto
      choledocholithiasis. A prospective randomized study was performed on 63
      consecutive cholecysto-choledocholithiasis patients during 2008 and 2011. The
      efficiency and safety of one-step procedure was assessed by comparing the two
      step LC with ERCP + endoscopic sphincterotomy (EST). Outcomes including
      intraoperative features, postoperative features (length of stay and postoperative
      complications) were evaluated. One- or two-step procedure of LC with ERCP + EST
      was successfully performed in all patients, and common bile duct stones were
      completely removed. Statistical analyses showed that length of stay and pulmonary
      infection rate were significantly lower in the test group compared with that in
      the control group (P < 0.05), whereas no statistical difference in other outcomes
      was found between the two groups (all P > 0.05). The one-step procedure of LC
      with ERCP + EST is superior to the two-step procedure for treatment of patients
      with cholecysto-choledocholithiasis regarding to the reduced hospital stay and
      inhibited occurrence of pulmonary infections. Compared with two-step procedure,
      one-step procedure of LC with ERCP + EST may be a superior option for cholecysto
      choledocholithiasis patients treatment regarding to hospital stay and pulmonary
      infections.

PMID- 29183530
TI  - Identifying Barriers to Microlaparoscopy in the Performance of Surgical
      Procedures.

PMID- 29183531
TI  - Patterns of Recurrence and Mechanisms of Failure after Open Ventral Hernia Repair
      with Mesh.
AB  - Recurrence after ventral hernia repair (VHR) remains a significant complication.
      We sought to identify the technical aspects of VHR associated with recurrence.
      Patients who underwent open midline VHR between 2006 and 2013 (n = 261) were
      retrospectively evaluated. Patients with recurrence (Group 1, n = 48) were
      compared with those without recurrence (Group 2, n = 213). Smoking, diabetes, and
      body mass index were not different between groups. More patients in Group 1
      underwent clean-contaminated, contaminated, or dirty procedures (43.8 vs 27.7%; P
      = 0.021). Group 1 had a higher incidence of surgical site occurrence (52.1 vs
      32.9%; P = 0.020) and surgical site infection (43.8 vs 15.5%; P < 0.001).
      Recurrences were due to central mesh failure (CMF) (39.6%), midline recurrence
      after biologic or bioabsorbable mesh repair (18.8%), superior midline (16.7%),
      lateral (16.7%), and after mesh explantation (12.5%). Most CMF (78.9%) occurred
      with light-weight polypropylene (LWPP). Recurrence was higher if the midline
      fascia was unable to be closed. Recurrence with midweight polypropylene (MWPP)
      was lower than biologic (P < 0.001), bioabsorbable (P = 0.006), and light-weight
      polypropylene (P = 0.046) mesh. Fixation, component separation technique, and
      mesh position were not different between groups. Wound complications are
      associated with subsequent recurrence, whereas midweight polypropylene is
      associated with a lower overall risk of recurrence and, specifically, CMF.

PMID- 29183532
TI  - Descriptive Analysis of Venous Thromboembolism in Georgia Trauma Centers Compared
      with National Trauma Centers Participating in the Trauma Quality Improvement
      Program.
AB  - This study was designed to compare the incidence of venous thromboembolism (VTE)
      in Georgia trauma centers with other national trauma centers participating in the
      Trauma Quality Improvement Program (TQIP). The use of chemoprophylaxis and
      characteristics of patients who developed VTE were also examined. We conducted a
      retrospective observational study of 325,703 trauma admissions to 245 trauma
      centers from 2013 to 2014. Patient demographics, rate of VTE, as well as the use,
      type, and timing of chemoprophylaxis were compared between patients admitted to
      Georgia and non-Georgia trauma centers. The rate of VTE in Georgia trauma centers
      was 1.9 per cent compared with 2.1 per cent in other national trauma centers.
      Overall, 49.6 per cent of Georgia patients and 45.5 per cent of patients in other
      trauma centers had documented chemoprophylaxis. Low molecular weight heparin was
      the most commonly used medication. Most patients who developed VTE did so despite
      receiving prophylaxis. The rate of VTE despite prophylaxis was 3.2 per cent in
      Georgia and 3.1 per cent in non-Georgia trauma centers. Mortality associated with
      VTE was higher in Georgia trauma centers compared with national TQIP benchmarks.
      The incidence of VTE and use of chemoprophylaxis within Georgia trauma centers
      were similar to national TQIP data. Interestingly, most patients who developed
      VTE in both populations received VTE prophylaxis. Further research is needed to
      develop best-practice guidelines for prevention, early detection, and treatment
      in high-risk populations.

PMID- 29183533
TI  - Predictive Factors for Treatment Failure after Peritoneovenous Shunt for Hepatic
      Ascites.
AB  - Peritoneovenous shunt (PVS) is used to treat refractory ascites. Here, we
      identify predictive factors for inhospital death after PVS placement. Thirty-five
      patients with refractory ascites related to liver cirrhosis and/or hepatocellular
      carcinoma (HCC) who underwent PVS placement between February 2005 and February
      2013 were included in the study. Group A comprised 13 patients for whom the PVS
      placement outcome was inhospital death. Group B comprised 22 patients who were
      discharged after PVS placement without complications. Patient background and
      laboratory data were analyzed to identify risk factors for inhospital death. HCC
      prevalence in Groups A and B was 92 and 55 per cent, respectively (P = 0.02) and
      that of portal venous tumor thrombus (PVTT) was 54 and 9 per cent, respectively
      (P = 0.003). The mean des-gamma-carboxy prothrombin (DCP) level in both groups
      was 15,553 +/- 49,330 and 787 +/- 2600 mAU/mL, respectively (P = 0.009).
      Multivariate analysis revealed that the presence of PVTT was the only independent
      predictor of inhospital death (P = 0.007). The presence of PVTT, HCC, and
      elevated des-gamma-carboxy prothrombin levels are predictors of inhospital death
      after PVS placement. Therefore, PVS should not be used to treat refractory
      ascites in patients with these predictors, particularly with PVTT.

PMID- 29183534
TI  - Papillary Breast Lesions: Association with Malignancy and Upgrade Rates on
      Surgical Excision.
AB  - Intraductal papilloma falls under the category of benign breast mass. However,
      recent studies show that it can harbor occult carcinoma. The management of benign
      intraductal papilloma remains controversial because of its nonspecific radiologic
      and histological findings, as well as its association with surrounding malignant
      pathology. The purpose of this study is to investigate upgrade rates of a benign
      intraductal papilloma on surgical excision and the need for surgical excision of
      papillary lesions diagnosed at core needle biopsy. A retrospective review of a
      single institution's pathology database between 2011 and 2015 identified 43 core
      biopsies with benign papilloma. We followed the upgrade rates of these lesions on
      surgical excision. There were 90 biopsies with the diagnosis of benign
      intraductal papilloma. The average age was 55.2 (range from 24-87 years old).
      Forty-three had benign intraductal papilloma; 28 of the 43 core biopsies had
      surgical excision. Two (7.1%) had an upgrade from benign intraductal papilloma to
      intraductal papilloma with atypia. One (3.6%) had an upgrade to ductal carcinoma
      in situ. None had invasive cancer. Surgical findings were in agreement with core
      biopsies in 25 (89.3%) of 28 cases (kappa = 0.80, P < 0.0001). Core biopsies have
      a statistically significant correlation with pathologies on surgical excision in
      detecting atypia in breast lesion as demonstrated by kappa = 0.80. However, the
      study shows benign intraductal papillomas on core biopsy have an upgrade rate of
      10.7 per cent after undergoing surgical excision. As such, we recommend a more
      aggressive approach including surgical excision of all benign intraductal
      papillary lesions.

PMID- 29183535
TI  - Major General Malcolm C. Grow, M.D. (1887-1960) Soldier, Surgeon, Airman.
AB  - World War I (WWI) and World War II (WWII) both presented physicians with
      challenges unseen before in history. New inventions such as the machine gun and
      poisonous gas in WWI and the massive aircraft battles in WWII required physicians
      and surgeons to adapt and innovate to provide the best care and preventative
      measures for service members. One physician, Malcolm Cummings Grow, distinguished
      himself as an innovator, a researcher, and a leader. His contributions to the
      field of military medicine, flight surgery, and medical administration led to
      countless lives being saved during the two World Wars and laid the groundwork for
      many different combat protective equipment still in use today.

PMID- 29183536
TI  - A Preliminary Analysis of Compassion Fatigue in a Surgeon Population: Are Female
      Surgeons at Heightened Risk?
AB  - Compassion fatigue (CF), a state of physical/emotional distress caused by
      repeatedly caring for those experiencing traumatic episodes, is a prevalent issue
      for today's healthcare provider. We sought to characterize levels of CF within a
      surgeon population, particularly comparing trauma surgery with other surgical
      specialties. A survey containing the Professional Quality of Life Scale (ProQOL),
      a validated tool assessing compassion satisfaction (CS), CF, and burnout (BO) was
      distributed via electronic newsletter to members of the American College of
      Surgeons. Demographic data and Professional Quality of Life Scale scores for CS,
      BO, and CF were collected and compared within specialty and gender subgroups. A
      total of 178 surgeons completed surveys. Respondents were predominantly male,
      general surgeons, >55 years old. Trauma surgeons composed the second largest
      subgroup. Levels of CS were significantly lower in the trauma surgeon subgroup
      compared to other surgical specialties (trauma: 37.1 +/- 5.28, other: 39.5 +/-
      6.30; P = 0.044). Female surgeons from all specialties exhibited significantly
      higher levels of BO (female: 26.7 +/- 6.10, male: 24.6 +/- 6.79; P = 0.035) and
      CF (female: 24.2 +/- 6.29, male: 21.9 +/- 6.11; P = 0.021) compared with male
      surgeons. Subanalyses comparing female trauma surgeons to female surgeons in
      other specialties found female trauma surgeons exhibited significantly lower
      levels of CS (trauma: 34.8 +/- 4.63, other: 38.8 +/- 5.99; P = 0.038) and higher
      levels of BO (trauma: 29.1 +/- 3.14, other: 25.3 +/- 6.41; P = 0.049). Trauma
      surgeons, particularly female trauma surgeons, may be at a heightened risk for
      developing a poorer overall professional quality of life compared with surgeons
      of other specialties. In addition, female surgeons may be at greater risk for
      developing CF compared with male counterparts.

PMID- 29183537
TI  - Continuing Trauma: The Unmet Needs of Trauma Patients in the Postacute Care
      Setting.
AB  - Trauma care has traditionally focused on prehospital and hospital settings, yet
      many injured patients report emotional distress in the postacute care setting,
      which is known to impair recovery. The objective of this study was to assess
      postdischarge emotional recovery and communication preferences. An observational
      cohort of 100 adult patients from our Level 1 Trauma Center was surveyed one to
      two months postdischarge. Among those employed preinjury, 44 per cent had not
      returned to work. Nearly half screened positive for emotional issues
      (posttraumatic stress disorder, depression, and/or psychological distress); of
      these, only 35 per cent considered getting professional help and only 10 per cent
      received help. The barrier most cited (58%) was cost; 42 per cent did not know
      how or where to get help. Most participants responded "no" or "I don't know" when
      asked if they had received information about coping with negative emotions after
      injury and how to seek help from a doctor to address these emotions. Two-thirds
      preferred to receive such information via phone call from a health care provider
      or by text. Eighty-nine per cent owned a cellphone. Our trauma systems are
      failing to provide comprehensive care or look at the ultimate outcomes of our
      patients, yet modern technology could provide needed resources to patients in
      novel ways.

PMID- 29183538
TI  - Laparoscopic Hyperthermic Intraperitoneal Chemotherapy for Peritoneal
      Carcinomatosisfrom Gastric Cancer: Its Beneficial Effects on Reduction and Exact
      Evaluation of the Peritoneal Cancer Index.
AB  - We assessed whether the laparoscopic hyperthermic intraperitoneal chemotherapy (L
      HIPEC) + neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) could
      reduce the peritoneal cancer index (PCI; which is defined by Sugerbaker) and
      improve the possibility to obtain a complete cytoreductive surgery (CRS with
      peritonectomy; basically according to the Sugerbaker's procedure). After L-HIPEC
      + NIPS, the PCI score was decreased in 89.5 per cent of patients, and the average
      score was significantly reduced. The average PCI reduction of improved PCI cases
      was 10.2 +/- 8.4. The hypothetical cut-off was at a PCI score of six with
      significant higher possibility of CRS completeness. Twelve patients had high-PCI
      (PCI > 6), and six of them (50.0%) were converted to low-PCI (PCI ? 6) and got a
      complete CRS. There was a significant relationship between post-PCI (PCI after L
      HIPEC + NIPS) and CRS completeness; however, pre-PCI (PCI before L-HIPEC + NIPS)
      value was not a relevant factor. The high-PCI and increased PCI even after L
      HIPEC + NIPS (deteriorated-PCI) were suggested as important risk factors for
      surgical completeness. Neither pre- nor postcytological results had a significant
      relationship between CRS completeness. However, the deteriorated cytological
      class was considered as a risk factor for CRS completeness. The second-look
      laparoscopy would be recommended for the better selection of the patients who can
      receive benefits by this extensive surgery.

PMID- 29183539
TI  - Electronic reporting improves timeliness and completeness of infectious disease
      notification, The Netherlands, 2003.
AB  - In 2002, the internet based reporting system OSIRIS was introduced in the
      Netherlands and by the end of that year had fully replaced the paper-based
      reporting system. The objectives of OSIRIS were to improve timeliness and
      completeness of surveillance data on infectious diseases reported from regional
      to national level. We compared the timeliness of infectious diseases reported by
      the conventional paper-based system in 2001 with those reported by OSIRIS in
      2003. Two distinct types of delay were compared: total delay: defined as time
      between sympton onset and reporting at national level and central delay: defined
      as time between regional and national reporting. Median delays between both
      systems were compared using the Wilcoxon Rank Sum-Test. We also compared
      electronic reports received via OSIRIS in 2003 to those received through the
      conventional system for 2001 for completeness of specific data fields. The Fisher
      exact test and the Mantel-Haenzel test with Yates correction were used to
      determine the significance of proportions of completed data fields in each
      system.

PMID- 29183540
TI  - Panton-Valentine leukocidin positive MRSA in 2003: the Dutch situation.
AB  - Analysis of methicillin-resistant Staphylococcus aureus (MRSA) isolates in the
      Netherlands in 2003 revealed that 8% of the hospital isolates carried the loci
      for Panton-Valentine leukocidin (PVL). Molecular subtyping showed that most Dutch
      PVL-MRSA genotypes corresponded to well-documented global epidemic types. The
      most common PVL-MRSA genotypes were sequence type ST8, ST22, ST30, ST59 and ST80.
      MRSA with ST8 increased in the Netherlands from 1% in 2002 to 17% in 2003. It is
      emphasised that PVL-MRSA might not only emerge in the community, but also in the
      hospital environment.

PMID- 29183541
TI  - Pulmonary tuberculosis in two remand prisons (SIZOs) in St Petersburg, Russia.
AB  - The tuberculosis (TB) situation in the Russian penitentiary system has received
      much attention. We performed a descriptive epidemiological study of TB in two St
      Petersburg remand prisons (SIZOs). The medical databases of the TB divisions in
      these prisons were searched for all diagnosed cases of TB from 1 January 2000 to
      31 December 2002. The main diagnostic method was chest x ray. The total number of
      reported TB cases in these two remand prisons during this three-year period was
      876. Out of these, 432 were diagnosed at entry to prison, and 444 developed the
      disease during incarceration, with the proportion diagnosed during incarceration
      increasing over time. The majority of cases were aged under 30 years. TB
      incidence in Russian remand prisons is still very high and needs to be monitored
      closely.

PMID- 29183542
TI  - Acute hepatitis C infection in HIV positive men who have sex with men in Paris,
      France, 2001-2004.
AB  - In mid-2004, three Parisian hospital wards informed the Institut de veille
      sanitaire of recent acute hepatitis C in HIV-infected (HIV+) men who had sex with
      men (MSM). These cases for whom none of the usual bloodborne routes for hepatitis
      C (HCV) transmission was found, reported having had unprotected sex. In October
      2004, we conducted a retrospective investigation in Parisian hospital wards to
      explore HCV modes of transmission in recent acute hepatitis C in HIV+ MSM.
      Patient demographics, clinical and biological status of HIV infection, reasons
      for HCV testing, sexual behaviour and risk factors for HCV transmission within
      the 6 months before hepatitis onset were collected from medical records. An
      anonymous self-administered questionnaire on sexual behaviour within the six
      months before hepatitis onset was also offered to all cases. We identified 29
      cases of acute hepatitis C in HIV+ MSM with onset from April 2001 to October
      2004. HIV infection was asymptomatic for 76%. Median age at hepatitis C onset was
      40 (28-54) years. In all records, were noted unprotected anal sex, fisting in 21%
      and a concomitant sexually transmitted infection (STI) in 41%. Median time
      between HIV diagnosis and HCV infection was 6.5 years (0-22). From the 11 self
      administered questionnaires completed, 10 reported an STI, 8 "hard" sexual
      practices, 6 bleeding during sex and 5 fisting. HCV transmission probably
      occurred through bleeding during unprotected traumatic anal sex among HIV+ MSM
      and may be facilitated by STI mucosal lesions. This report stresses the
      continuous need to strongly advocate safer sex to MSM.

PMID- 29183543
TI  - Estimates of the frequency of HBV, HCV, and HIV infectious donations entering the
      blood supply in the United Kingdom, 1996 to 2003.
AB  - Several new tests have been recently introduced by the United Kingdom Blood
      Services to improve safety. The frequency (or risk) of hepatitis B virus (HBV),
      hepatitis C virus (HCV) and HIV infectious donations entering the UK blood supply
      during 1996-2003 has been estimated. These years span the introduction of nucleic
      acid testing (NAT) for HCV, HIV combination antigen and antibody test and NAT for
      HIV. The frequency of an infectious donation entering the blood supply due to i)
      the window period, ii) assay failures and iii) human and technical errors in
      testing and processing, was estimated. The window period risk was estimated using
      the incidence of infection in donors and the length of the window period for
      tests in use, with an adjustment for atypical inter-donation intervals in
      seroconverting donors. The estimated frequency of infectious donations entering
      the blood supply during 1996-2003 was 1.66, 0.80 and 0.14 per million for HBV,
      HCV and HIV respectively. HCV NAT resulted in an over 95% fall in the risk of
      HCV. Current usage of HIV combined antibody-antigen tests and of HIV NAT reduced
      the estimated risk of HIV by 10%. Since 1996, the risk of transfusion-transmitted
      HBV, HCV and HIV infection in the UK has been lowered by several improvements to
      donation testing, although the absolute reduction in risk has been small.
      Vigilance for errors and the affects of donor selection may be as or more
      important than further reductions to window periods of tests for improving blood
      safety with respect to HBV, HCV and HIV.

PMID- 29183544
TI  - Bichat guidelines for the clinical management of Q fever and bioterrorism-related
      Q fever.
AB  - Q fever is a zoonotic disease caused by Coxiella burnetii. Its interest as a
      potential biological weapon stems from the fact that an aerosol of very few
      organisms could infect humans. Another route of transmission of C. burnetii could
      be through adding it to the food supply. Nevertheless, C. burnetii is considered
      to be one of the less suitable candidate agents for use in a bioterrorist attack;
      the incubation is long, many infections are inapparent and the mortality is low.
      In the case of an intentional release of C. burnetii by a terrorist, clinical
      presentation would be similar to naturally occurring disease. It may be
      asymptomatic, acute, normally accompanied by pneumonia or hepatitis, or chronic,
      usually manifested as endocarditis. Most cases of acute Q fever are asymptomatic
      and resolve spontaneously without specific treatment. Nevertheless, treatment can
      shorten the duration of illness and decrease the risk of complications such as
      endocarditis. Post-exposure prophylaxis is recommended after the exposure in the
      case of a bioterrorist attack.

PMID- 29183545
TI  - Bichat guidelines for the clinical management of viral encephalitis and
      bioterrorism-related viral encephalitis.
AB  - Most of the viruses involved in causing encephalitis are arthropod-borne viruses,
      with the exception of arenaviruses that are rodent-borne. Even if little
      information is available, there are indications that, most of these encephalitis
      associated viruses could be used by aerosolisation during a bioterrorist attack.
      Viral transfer from blood to the CNS through the olfactory tract has been
      suggested. Another possible route of contamination is by vector-borne
      transmission such as infected mosquitoes or ticks. Alphaviruses are the most
      likely candidates for weaponisation. The clinical course of the diseases caused
      by these viruses is usually not specific, but differentiation is possible by
      using an adequate diagnostic tool. There is no effective drug therapy for the
      treatment of these diseases and treatment is mainly supportive, but vaccines
      protecting against some of these viruses do exist.

PMID- 29183546
TI  - Surveillance of antimicrobial resistance in Bulgaria - a synopsis from BulSTAR
      2003.
AB  - We introduce Bulgarian Surveillance Tracking Antimicrobial Resistance (BulSTAR)
      and make the first report on surveillance data for 2003. This longitudinal
      surveillance programme monitors the isolation and antimicrobial susceptibility of
      all clinically significant microorganisms isolated from blood cultures,
      cerebrospinal fluid, upper and lower respiratory tract, urine and wound samples
      in the participating microbiology laboratories. Twenty eight public, 45 hospital
      and 6 private laboratories from all 28 counties of the Republic of Bulgaria
      participated in BulSTAR 2003. The total number of isolates from monitored sources
      during the surveillance period was 98 929. Seven microorganisms represented 72%
      of all isolated bacteria in BulSTAR 2003: Escherichia coli, Staphylococcus
      aureus, Proteus-Providencia-Morganella group, Klebsiella spp., Pseudomonas spp,
      Streptococcus pneumoniae and Streptococcus pyogenes. Generally the resistance of
      clinically significant Gram positive and Gram negative bacteria in Bulgaria was
      estimated to be at a medium level when compared with many other surveillance
      sources worldwide. A unique 32-year experiment on the population by treating all
      severe infections with an ampicillin/gentamicin combination resulted in twofold
      higher levels of resistance to amynoglycosides compared with other countries
      worldwide. This is due to the extremely conservative treatment schemes used in
      the former socialist countries, based on national directives and cheap domestic
      production of gentamicin and ampicillin. The forthcoming introduction of a
      computer network and improvements in detecting mistakes are expected to increase
      the sensitivity and the significance of BulSTAR surveillance system - an
      indispensable tool in the combat against increasing worldwide antibiotic
      resistance.

PMID- 29183548
TI  - Travellers returning to Sweden as sentinels for comparative disease incidence in
      other European countries, campylobacter and giardia infection as examples.
AB  - Comparable figures on disease incidence between countries are difficult to
      attain. We therefore compared risk of infection for Swedes going to other
      European countries. We took as the numerator the number of imported cases from
      European countries of campylobacter and giardia infection in the national Swedish
      surveillance database, and as the denominator, the number of visitors to each
      country from a commercial database on foreign travel. Risk of infection in
      tourists was also compared to national incidence figures for a selection of
      countries.

PMID- 29183549
TI  - Communicable disease control in a migrant seasonal workers population: A case
      study in Norway.
AB  - Reliable data on the health status of migrant seasonal workers in Europe is
      scarce. Access to public health care for this population depends on national
      regulations, and their legal status in host countries. In this manuscript we
      describe a case study of a salmonellosis outbreak that occurred in Norway, and
      highlight the difficulties encountered in applying control measures in a
      population of seasonal migrant farm workers. Surveillance and control of
      infectious diseases need to be supported by legislation which makes
      implementation of control measures possible. Efforts have been made to improve
      the rights for migrants in Europe with regard to healthcare, but seasonal migrant
      workers still remain largely outsiders where these measures are concerned.
      Special attention should be given to this disadvantaged group in terms of social
      rights and healthcare. Preparedness plans should be improved to deal with
      contagious pathogens involving the seasonal migrant population.

PMID- 29183550
TI  - Prevention of congenital rubella infection: a challenge for every country in
      Europe.
AB  - The current issue of Eurosurveillance provides the common theme of the
      epidemiology and control of congenital rubella infection (CRI) across Europe. It
      provides a stark reminder that despite the availability of a safe and effective
      vaccine for many years, CRI - the consequence of rubella infection during
      pregnancy, remains an important public health problem both in the European Union
      and the wider WHO European Region. The following articles outline the various
      operational challenges facing national immunisation programmes in Europe. They
      vividly illustrate large differences in disease burden and inequalities in access
      to preventive health services both between and within countries. Four groups of
      countries can be distinguished.

PMID- 29183551
TI  - Preliminary results from the new HIV surveillance system in France.
AB  - In addition to AIDS surveillance, data on HIV infection are necessary to better
      follow the dynamics of the epidemic. We report the first results of France's
      mandatory anonymous HIV notification system, which is linked to a virological
      surveillance of recent HIV infections and of circulating HIV types, groups and
      subtypes. HIV notifications are initiated by microbiologists who create an
      anonymous code of patient's identity. Clinicians complete the notification form
      with epidemiological and clinical data. Notifications are sent to the local
      health authorities and passed to the Institut de Veille Sanitaire (InVS).

PMID- 29183552
TI  - Detection of adamantane-sensitive influenza A(H3N2) viruses in Australia, 2017: a
      cause for hope?
AB  - For over a decade virtually all A(H3N2) influenza viruses have been resistant to
      the adamantane class of antivirals. However, during the 2017 influenza season in
      Australia, 15/461 (3.3%) adamantane-sensitive A(H3N2) viruses encoding serine at
      residue 31 of the M2 protein were detected, more than the total number identified
      globally during the last 6 years. A return to wide circulation of adamantane
      sensitive A(H3N2) viruses would revive the option of using these drugs for
      treatment and prophylaxis.

PMID- 29183553
TI  - Childhood multidrug-resistant tuberculosis in the European Union and European
      Economic Area: an analysis of tuberculosis surveillance data from 2007 to 2015.
AB  - BackgroundConfirming tuberculosis (TB) in children and obtaining information on
      drug susceptibility is essential to ensure adequate treatment. We assessed
      whether there are gaps in diagnosis and treatment of multidrug-resistant (MDR) TB
      in children in the European Union and European Economic Area (EU/EEA), quantified
      the burden of MDR TB in children and characterised cases. Methods: We analysed
      surveillance data from 2007 to 2015 for paediatric cases younger than 15 years.
      Results: In that period, 26 EU/EEA countries reported 18,826 paediatric TB cases
      of whom 4,129 (21.9%) were laboratory-confirmed. Drug susceptibility testing
      results were available for 3,378 (17.9%), representing 81.8% of the confirmed
      cases. The majority (n = 2,967; 87.8%) had drug-sensitive TB, 249 (7.4%) mono
      resistant TB, 64 (1.9%) poly-resistant TB, 90 (2.7%) MDR TB and eight (0.2%) had
      extensively drug-resistant (XDR) TB. MDR TB was more frequently reported among
      paediatric cases with foreign background (adjusted odds ratio (aOR) = 1.73; 95%
      confidence interval (95% CI): 1.12-2.67) or previous TB treatment (aOR: 6.42; 95%
      CI: 3.24-12.75). Successful treatment outcome was reported for 58 of 74
      paediatric MDR TB cases with outcome reported from 2007 to 2013; only the group
      of 5-9 years-olds was significantly associated with unsuccessful treatment
      outcome (crude odds ratio (cOR) = 11.45; 95% CI: 1.24-106.04). Conclusions: The
      burden of MDR TB in children in the EU/EEA appears low, but may be underestimated
      owing to challenges in laboratory confirmation. Diagnostic improvements are
      needed for early detection and adequate treatment of MDR TB. Children previously
      treated for TB or of foreign origin may warrant higher attention.

PMID- 29183554
TI  - Molecular characterisation of human Shiga toxin-producing Escherichia coli O26
      strains: results of an outbreak investigation, Romania, February to August 2016.
AB  - IntroductionAt the beginning of 2016, an increase in paediatric haemolytic uremic
      syndrome (HUS) cases was observed in Romania. The microbiological investigations
      allowed isolation of Shiga toxin-producing Escherichia coli (STEC) O26 as the
      causative agent from most cases. Methods: An enhanced national surveillance of
      HUS and severe diarrhoea was established across the country following the
      identification of the first cases and was carried out until August 2016. A total
      of 15 strains were isolated from 10 HUS and five diarrhoea cases. Strains were
      characterised by virulence markers (i.e. stx type/subtype, eae, ehxA genes),
      phylogroup, genetic relatedness and clonality using PCR-based assays, PFGE and
      multilocus sequence typing (MLST). The first six strains were further
      characterised by whole genome sequencing (WGS). Results: Five PCR-defined
      genotypes were distinguished. All strains from HUS cases harboured stx2a and eae,
      with or without stx1a, while strains from diarrhoea cases carried exclusively
      stx1a and eae genes. PFGE resolved strains into multiple pulsotypes, compatible
      with a certain geographic segregation of the cases, and strains were assigned to
      phylogroup B1 and sequence type (ST) 21. WGS confirmed the results of
      conventional molecular methods, brought evidence of O26:H11 serotype, and
      complemented the virulence profiles. Discussion/conclusion: This first
      description of STEC O26 strains from cases in Romania showed that the isolates
      belonged to a diverse population. The virulence content of most strains
      highlighted a high risk for severe outcome in infected patients. Improving the
      national surveillance strategy for STEC infections in Romania needs to be further
      considered.

PMID- 29183556
TI  - Syphilis surveillance and trends of the syphilis epidemic in Germany since the
      mid-90s.
AB  - Recent surveillance reports from Europe and the United States show an increase in
      syphilis cases. Accurate epidemiological information about the distribution of
      syphilis is important for targeting screening and intervention programmes. The
      German syphilis notification system changed in 2001 from physician to laboratory
      based reporting, which is complemented by a newly introduced sexually transmitted
      infection (STI) sentinel system. After reaching an all time low during the 1990s,
      syphilis notifications have increased significantly since 2001, coinciding with
      the introduction of the new reporting system. However, the increased reported
      incidence is reflecting a true rise in the number of cases and is not
      predominantly determined by more underreporting through the previous reporting
      system. The increase reflects syphilis outbreaks among men who have sex with men
      (MSM). The first of these outbreaks was observed in Hamburg in 1997. In 2003,
      incidence in men was ten times higher than in women. An estimated 75% of syphilis
      cases are currently diagnosed among MSM. A high proportion (according to sentinel
      data, up to 50%) of MSM diagnosed with syphilis are HIV positive. The
      continuously high number of syphilis cases diagnosed among heterosexuals in
      Germany in recent years compared with other western European countries may
      reflect the higher population movement between Germany and syphilis high
      incidence regions in south-east and eastern Europe.

PMID- 29183557
TI  - Occurrence of Salmonella Enteritidis phage type 29 in Austria : an opportunity to
      assess the relevance of chicken meat as source of human salmonella infections.
AB  - Assuming that the various phage types of Salmonella Enteritidis (S. Enteritidis)
      are largely equally virulent, the importance of certain foods as sources of
      infection for human salmonellosis can be deduced from differences in the
      distribution of phage types in human and non-human samples. In 2002, S.
      Enteritidis phage type 29 (PT29) was first isolated from non-human test samples
      in Austria. S. Enteritidis PT29 accounted for 44 (27.7%) of 159 S. Enteritidis
      strains, derived from veterinary samples of chicken (e.g. meat, giblets) or
      chicken habitations (e.g. swabs from the coop and excrement). At the food retail
      level (chicken meat, chicken liver), five (13.1%) of 38 S. Enteritidis isolates
      were PT29. The proportion of S. Enteritidis PT29 in human samples was much lower.
      Only 0.4% (30 human primary isolates) of all S. Enteritidis isolates in the year
      2002, and 0.33% (23 human primary isolates) of all human S. Enteritidis strains
      in 2003 were PT29. In our opinion, the discrepancy between the high prevalence of
      S. Enteritidis PT29 in broilers and chicken meat and the low number of PT29 cases
      in humans indicates that chicken meat of Austrian origin is currently only a
      minor source of human S. Enteritidis infections.

PMID- 29183555
TI  - Enhanced Bordetella pertussis acquisition rate in adolescents during the 2012
      epidemic in the Netherlands and evidence for prolonged antibody persistence after
      infection.
AB  - IntroductionIn 2012 a large epidemic of pertussis occurred in the Netherlands. We
      assessed pertussis toxin (PT) antibody levels in longitudinal serum samples from
      Dutch 10-18 year-olds, encompassing the epidemic, to investigate pertussis
      infection incidence. Methods: Blood was sampled in October 2011 (n = 239
      adolescents), then 1 year (2012; n = 228) and 3 years (2014; n = 167) later. PT
      IgG concentrations were measured by immunoassay and concentrations >=50 IU/mL
      (seropositive) assumed indicative of an infection within the preceding year.
      Results: During the 2012 epidemic, 10% of participants became seropositive, while
      this was just 3% after the epidemic. The pertussis acquisition rate proved to be
      sixfold higher during the epidemic (97 per 1,000 person-years) compared with 2012
      2014 (16 per 1,000 person-years). In 2012, pertussis notifications among
      adolescents nationwide were 228/100,000 (0.23%), which is at least 40 times lower
      than the seropositivity percentage. Remarkably, 17 of the 22 seropositive
      participants in 2011, were still seropositive in 2012 and nine remained
      seropositive for at least 3 years. Discussion: Longitudinal studies allow a
      better estimation of pertussis infections in the population. A PT-IgG
      concentration >=50 IU/mL as indication of recent infection may overestimate these
      numbers in cross-sectional serosurveillance and should be used carefully.

PMID- 29183558
TI  - The incidence of S. aureus bacteraemia in acute hospitals of the Mid-Western
      Area, Ireland, 2002-2004.
AB  - Concerns about healthcare-associated infections and the global crisis in
      antimicrobial resistance has combined to accentuate the fears around so-called
      "superbugs". In Ireland there is no single agreed indicator regarded as a true
      measure of the level of methicillin resistant Staphylococcus aureus (MRSA) in
      hospitals. The objective of this study was to compare two crude measures of MRSA 
      the percentage of bacteraemia caused by MRSA and the incidence rate (per 1000
      bed days used) of MRSA bacteraemia in six acute hospitals. We examined all blood
      cultures positive for S. aureus (methicillin sensitive and resistant) from 2002
      to 2004 in the Health Service Executive (HSE) Mid-Western Area of Ireland.
      Hospital In-Patient Enquiry (HIPE) data was used to determine monthly in-patient
      bed days used. Of 245 patient episodes of bacteraemia, 119 were MRSA. The trends
      in the percentage of isolates that were MRSA and the incidence rate calculated
      were compared. The incidence rate appears to be a more reliable and robust
      indicator of MRSA in hospitals than the percentage. Despite many difficulties in
      interpreting indicators of MRSA they should not preclude the regular publication
      of data at least at regional level in Ireland.

PMID- 29183559
TI  - Hospital preparedness and management of patients affected by viral haemorrhagic
      fever or smallpox at the Lazzaro Spallanzani Institute, Italy.
AB  - The US cases of anthrax in 2001 and the recent severe acute respiratory syndrome
      outbreak have heightened the need for preparedness and response to naturally
      emerging and re-emerging infections or deliberately released biological agents.
      This report describes the response model of the Istituto Nazionale per le
      Malattie Infettive Lazzaro Spallanzani (INMI), Rome, Italy for managing patients
      suspected of or affected by smallpox or viral haemorrhagic fever (VHF) either in
      the context of an intentional release or natural occurrence. The INMI is Italy's
      leading hospital in its preparedness and response plan to bioterrorism-related
      infectious agents. All single and double rooms of INMI are equipped with negative
      air pressure, sealed doors, high efficiency particulate air (HEPA) filters and a
      fully-equipped anteroom; moreover, a dedicated high isolation unit with a
      laboratory next door for the initial diagnostic assays is available for admission
      of sporadic patients requiring high isolation. For patient transportation, two
      fully equipped ambulances and two stretcher isolators with a negative pressure
      section are available. Biomolecular and traditional diagnostic assays are
      currently performed in the biosafety level 3/4 (BSL 3/4) laboratories. Continuing
      education and training of hospital staff, consistent application of infection
      control practices, and availability of adequate personnel protective equipment
      are additional resources implemented for the care of highly infectious patients
      and to maintain the readiness of an appropriately trained workforce to handle
      large scale outbreaks.

PMID- 29183560
TI  - Syphilis surveillance and epidemiology in the United Kingdom.
AB  - The aim of this article is to describe trends in infectious syphilis in the UK,
      and specifically the epidemiology of the London syphilis outbreak, the largest in
      the UK to date. Analysis of routine surveillance data from genitourinary medicine
      (GUM) clinics was performed as well as data collection through enhanced
      surveillance systems. There have been substantial increases in diagnoses of
      infectious syphilis between 1998 and 2003, with a 25-fold increase seen in men
      who have sex with men (MSM) (from 43 to 1028 diagnoses); 6-fold (138 to 860) in
      heterosexual men and 3-fold (112 to 338) in women. The national rise in syphilis
      was driven by a series of local outbreaks, the first of which occurred in 1997.
      To date, 1910 cases have been reported in the London outbreak, first detected in
      April 2001. High rates of HIV co-infection were seen among MSM, with MSM likely
      to be of white ethnicity and born in the UK. In contrast, heterosexuals were more
      likely to be of black ethnicity and born outside the UK. Most syphilis infections
      were acquired in London. MSM bear the brunt of the national resurgence in
      infectious syphilis. Substantial rises in male heterosexual cases has resulted in
      a divergence between male heterosexual and female cases, which now requires
      further investigation.

PMID- 29183561
TI  - Human immunodeficiency virus, hepatitis C and hepatitis B infections among blood
      donors in Germany 2000-2002: risk of virus transmission and the impact of nucleic
      acid amplification testing.
AB  - Blood and plasma donations in Germany are collected by several institutions,
      namely the German Red Cross, community and hospital-based blood services, private
      blood centres, commercial plasma donation sites and transfusion services of the
      army. All blood donation centres are required to report quarterly data on
      infection markers to the Robert Koch Institute, thus providing current and
      accurate epidemiological data. The prevalence and incidence of relevant viral
      infections are low in the blood donor population in Germany, with a decreasing
      trend for hepatitis C infections in new and repeat donors since 1997. The
      implementation of mandatory nucleic acid amplification technique (NAT) testing
      for hepatitis C virus (HCV) in 1999 has markedly improved transfusion safety. HIV
      NAT became mandatory in 2004 but was done voluntarily by the majority of the
      blood donation services before then. The potential benefit of hepatitis B virus
      (HBV) minipool NAT is not as clear because chronic HBV carriers with very low
      virus levels might donate unidentified. The residual risk of an infectious window
      period donation inadvertently entering the blood supply can be estimated using a
      mathematic model which multiplies the incidence rate by the number of days during
      which an infection may be present but not detectable, i.e. the length of the
      window period. The risk of an undetected infection without NAT testing was
      estimated to be 1 in 2 770 000 for HIV, 1 in 670 000 for HCV and 1 in 230 000 for
      HBV in 2001/2002. This contrasts with 1 in 5 540 000 for HIV, 1 in 4 400 000 for
      HCV and 1 in 620 000 for HBV with minipool NAT testing. This demonstrates that
      NAT testing can further reduce the already very small risk of infectious
      donations entering the blood supply.

PMID- 29183562
TI  - High sensitivity for tuberculosis in a national integrated surveillance system in
      Finland.
AB  - Little is known about the sensitivity of surveillance for tuberculosis after
      integration of formerly dedicated tuberculosis surveillance and control into the
      general health care system, an integration which took place in Finland in 1987.
      We compared routine laboratory notifications to the National Infectious Disease
      Register (NIDR) for Mycobacterium tuberculosis from January 1, 1995, to December
      31, 1996, with data collected independently from all laboratories offering M.
      tuberculosis culture, and with data from patient records. 1059 culture-positive
      cases were found. The overall sensitivity of the NIDR was 93 % (984/1059). The
      positive predictive value of a culture-positive case in the NIDR to be a true
      culture-confirmed case was 99%. For the culture-confirmed cases in the NIDR, one
      or more physician notification forms had been submitted for 89%. A highly
      sensitive notification system for culture-positive tuberculosis can be achieved
      in an integrated national infectious disease surveillance system based on
      laboratory notification.

PMID- 29183563
TI  - A systematic review and economic evaluation of adalimumab and dexamethasone for
      treating non-infectious intermediate uveitis, posterior uveitis or panuveitis in
      adults.
AB  - BACKGROUND: Non-infectious intermediate uveitis, posterior uveitis and panuveitis
      are a heterogeneous group of inflammatory eye disorders. Management includes
      local and systemic corticosteroids, immunosuppressants and biological drugs.
      OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of
      subcutaneous adalimumab (Humira(r); AbbVie Ltd, Maidenhead, UK) and a
      dexamethasone intravitreal implant (Ozurdex(r); Allergan Ltd, Marlow, UK) in
      adults with non-infectious intermediate uveitis, posterior uveitis or panuveitis.
      DATA SOURCES: Electronic databases and clinical trials registries including
      MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts
      of Reviews of Effects and the World Health Organization's International Clinical
      Trials Registry Platform were searched to June 2016, with an update search
      carried out in October 2016. REVIEW METHODS: Review methods followed published
      guidelines. A Markov model was developed to assess the cost-effectiveness of
      dexamethasone and adalimumab, each compared with current practice, from a NHS and
      Personal Social Services (PSS) perspective over a lifetime horizon, parameterised
      with published evidence. Costs and benefits were discounted at 3.5%. Substantial
      sensitivity analyses were undertaken. RESULTS: Of the 134 full-text articles
      screened, three studies (four articles) were included in the clinical
      effectiveness review. Two randomised controlled trials (RCTs) [VISUAL I (active
      uveitis) and VISUAL II (inactive uveitis)] compared adalimumab with placebo, with
      limited standard care also provided in both arms. Time to treatment failure
      (reduced visual acuity, intraocular inflammation, new vascular lesions) was
      longer in the adalimumab group than in the placebo group, with a hazard ratio of
      0.50 [95% confidence interval (CI) 0.36 to 0.70; p < 0.001] in the VISUAL I trial
      and 0.57 (95% CI 0.39 to 0.84; p = 0.004) in the VISUAL II trial. The adalimumab
      group showed a significantly greater improvement than the placebo group in the 25
      item Visual Function Questionnaire (VFQ-25) composite score in the VISUAL I trial
      (mean difference 4.20; p = 0.010) but not the VISUAL II trial (mean difference
      2.12; p = 0.16). Some systemic adverse effects occurred more frequently with
      adalimumab than with placebo. One RCT [HURON (active uveitis)] compared a single
      0.7-mg dexamethasone implant against a sham procedure, with limited standard care
      also provided in both arms. Dexamethasone provided significant benefits over the
      sham procedure at 8 and 26 weeks in the percentage of patients with a vitreous
      haze score of zero (p < 0.014), the mean best corrected visual acuity improvement
      (p <= 0.002) and the percentage of patients with a >= 5-point improvement in VFQ
      25 score (p < 0.05). Raised intraocular pressure and cataracts occurred more
      frequently with dexamethasone than with the sham procedure. The incremental cost
      effectiveness ratio (ICER) for one dexamethasone implant in one eye for a
      combination of patients with unilateral and bilateral uveitis compared with
      limited current practice, as per the HURON trial, was estimated to be L19,509 per
      quality-adjusted life-year (QALY) gained. The ICER of adalimumab for patients
      with mainly bilateral uveitis compared with limited current practice, as per the
      VISUAL trials, was estimated to be L94,523 and L317,547 per QALY gained in active
      and inactive uveitis respectively. Sensitivity analyses suggested that the rate
      of blindness has the biggest impact on the model results. The interventions may
      be more cost-effective in populations in which there is a greater risk of
      blindness. LIMITATIONS: The clinical trials did not fully reflect clinical
      practice. Thirteen additional studies of clinically relevant comparator
      treatments were identified; however, network meta-analysis was not feasible. The
      model results are highly uncertain because of the limited evidence base.
      CONCLUSIONS: Two RCTs of systemic adalimumab and one RCT of a unilateral, single
      dexamethasone implant showed significant benefits over placebo or a sham
      procedure. The ICERs for adalimumab were estimated to be above generally accepted
      thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone was
      estimated to fall below standard thresholds. However, there is substantial
      uncertainty around the model assumptions. In future work, primary research should
      compare dexamethasone and adalimumab with current treatments over the long term
      and in important subgroups and consider how short-term improvements relate to
      long-term effects on vision. STUDY REGISTRATION: This study is registered as
      PROSPERO CRD42016041799. FUNDING: The National Institute for Health Research
      Health Technology Assessment programme.

PMID- 29183564
TI  - 'Lost and confused': parent representative groups' perspectives on child and
      family health services in Australia.
AB  - Consumer involvement in health care is widely accepted in policy and service
      delivery. Australia offers universal health services for families with children
      aged 0 to 5 years, provided by child and family health nurses and general
      practitioners. Services include, but are not limited to, monitoring and promoting
      child health and development, and supporting parents. This paper reports consumer
      representatives' perspectives on Australian parents' needs and experiences of
      child and family health services, identifying facilitators and barriers to
      service utilisation. Twenty-six representatives from consumer organisations
      explored families' experiences through focus groups. Qualitative data were
      analysed thematically. Consumer representatives identified several key
      implications for families using primary health services: feeling 'lost and
      confused' on the parenting journey; seeking continuity and partnership; feeling
      judged; and deciding to discontinue services. Participants highlighted
      accessible, timely, non-judgmental and appropriate interactions with healthcare
      professionals as vital to positive consumer experiences and optimal health and
      developmental outcomes. Representatives indicated that families value the
      fundamentals of well-designed health services: trust, accessibility, continuity,
      knowledge and approachability. However, both consumers and service providers face
      barriers to effective ongoing engagement in universally provided services.

PMID- 29183565
TI  - Health seeking narratives of unwell Sri Lankan Tamil refugees in Melbourne
      Australia.
AB  - Sri Lankan Tamil refugees are among the largest group of refugees to resettle in
      Australia in the last decade. The aim of this study is to characterise the
      narratives of health-seeking among unwell Sri Lankan Tamil refugees in Melbourne,
      Victoria, Australia. Drawing on a qualitative, phenomenological perspective, we
      conducted in-depth interviews in Tamil and English with 12 participants who
      identified as being unwell for 6 months or more. Findings revealed three
      narratives of health-seeking: the search for the 'good life' that was lost or
      never experienced, seeking help from familiar channels in an unfamiliar context,
      and the desire for financial and occupational independence. These three
      narratives are undergirded by the metanarrative of a hope-filled recovery. These
      narratives of Tamil refugees' lived experience provide new insights into clinical
      care and health service delivery.

PMID- 29183566
TI  - Application of pressure-derived myocardial fractional flow reserve in chronic
      hemodialysis patients.
AB  - BACKGROUND: Although fractional flow reserve (FFR) measurements during coronary
      angiography are performed in routine clinical practice, few studies have
      evaluated FFR measurements in dialysis patients. METHODS: We retrospectively
      studied 42 hemodialysis patients with suspected or known coronary artery disease
      (CAD) who underwent stress myocardial perfusion imaging and coronary angiography
      with FFR measurements for 61 coronary lesions. The cut-off value for FFR to
      detect myocardial ischemia was determined by receiver operating characteristic
      (ROC) curve analysis. RESULTS: There were 61 coronary vessels measured by FFR.
      The FFR range was 0.34-0.93 with a mean of 0.74+/-0.13. The ROC curve analysis
      revealed that the best cut-off value of FFR for detecting myocardial ischemia was
      0.76 (p<0.0001), with 70% sensitivity, 86% specificity, and 76% accuracy for
      myocardial ischemia. Compared with patients who had positive myocardial ischemia
      and an FFR<=0.76, those who had negative myocardial ischemia despite an FFR<=0.76
      had less left ventricular (LV) mass index, whereas patients who had positive
      myocardial ischemia despite an FFR>0.76 had greater LV mass indexor serum calcium
      phosphorus product. CONCLUSIONS: The cut-off value of FFR for myocardial ischemia
      in chronic hemodialysis patients is similar to that in other CAD patients.
      However, caution is necessary when FFR measurements are applied to dialysis
      patients with significantly increased LV mass index or serum calcium-phosphorus
      product.

PMID- 29183567
TI  - Defining and measuring dogmanship: A new multidisciplinary science to improve
      understanding of human-dog interactions.

PMID- 29183568
TI  - Vertical head and pelvic movement symmetry at the trot in dogs with induced
      supporting limb lameness.
AB  - Compensatory limb loading has been studied in lame dogs; however, little is known
      about how these compensations relate to motion of the head and pelvis, assessment
      of which is an important component of lameness examinations. The aim of this
      study was to describe the patterns of vertical head and pelvic motion symmetry at
      the trot in dogs with induced supporting limb lameness in the forelimbs or hind
      limbs. Ten sound dogs were trotted on a treadmill before and after temporary
      induction of moderate lameness (grade 2/5) in each limb. Reflective markers were
      located on the head, pelvis and right forelimb, and kinematic data were captured
      with a motion capture system. Upper body symmetry parameters were calculated,
      including differences in the highest (HDmax) and in the lowest (HDmin) positions
      of the head, and in the highest (PDmax) and in the lowest (PDmin) positions of
      the mid-pelvis, with a value of zero indicating symmetry. The head was lowered
      more during the sound limb stance phase and lowered less during the lame limb
      stance phase in supporting forelimb lameness (HDmin: 4.6mm in dogs when sound, 
      18.3mm when left limb lameness was induced and 20.5mm when right limb lameness
      was induced). The mid-pelvis was lowered more during the sound limb stance phase
      and lowered and lifted less during the lame limb stance phase in supporting hind
      limb lameness (PDmin: 1mm in dogs when sound, -10.1mm in left limb lameness and
      8.4mm in right limb lameness). The hip of the lame side, measured at the level of
      the greater trochanter, had an increased downwards displacement during the lame
      limb swing phase (-21mm in left hind limb lameness, P=0.005; 23.4mm in right hind
      limb lameness, P=0.007). Asymmetry in the lowering of the head or mid-pelvis is a
      more sensitive indicator of supporting forelimb and hind limb lameness,
      respectively, than asymmetry in the raising of the head. Increased displacement
      of the hip ('hip drop' of the lame side during its swing phase) is a good
      indicator of hind limb lameness in dogs.

PMID- 29183569
TI  - Development of a fibrinolysis assay for canine plasma.
AB  - Unbalanced coagulation and fibrinolysis leads to hemorrhage or thrombosis.
      Thromboelastography has been used to characterize hypo- and hyper-fibrinolysis in
      dogs, however the technique requires specialized instrumentation and proprietary
      reagents that limit its availability. The aim of this study was to develop a
      simple microplate method for assessment of fibrinolysis in canine plasma. Plasma
      from healthy dogs was mixed in a microwell plate with tissue factor, calcium,
      phospholipid and tissue plasminogen activator. Light absorbance was measured at
      regular intervals until return to baseline. Peak optical density (milli
      absorption units, mAU), formation velocity (mAU/s), lysis velocity (mAU/s) and
      area under the curve (mAU.s) were calculated. The influence of potential
      interferents, variation in fibrinogen and ex vivo addition of heparin and
      aminocaproic acid on assay performance was determined. Inter-day coefficients of
      variation were <=15% for all variables. Bilirubin<=1.88mg/dL and
      hemoglobin<=0.09mg/dL did not interfere with assay variables. Aminocaproic acid
      (40MUg/mL) and heparin (0.125U/mL) caused almost complete inhibition of
      fibrinolysis and coagulation, respectively. All variables except lysis velocity
      (R2=0.08) were associated with fibrinogen concentration (R2>0.8). This assay
      showed acceptable performance characteristics for measurement of fibrinolysis in
      normal canine plasma. The assay utilizes small volume citrate plasma samples and
      readily available instrumentation and reagents, is not influenced by mild to
      moderate hemolysis or icterus and detects the presence of fibrinolysis
      inhibitors.

PMID- 29183570
TI  - Post-operative outcomes of surgical and chemical castration with zinc gluconate
      in dogs presenting to veterinary field clinics.
AB  - The objective of this study was to characterize post-operative outcomes of
      chemical castration as compared to surgical castration performed by existing
      municipal field clinics. Fifty-four healthy adult male dogs underwent chemical
      castration with zinc gluconate solution and 55 healthy adult male dogs underwent
      surgical castration in veterinary field clinics. Dogs in each group were
      evaluated for swelling, inflammation, and ulceration (chemical castration) or
      dehiscence (surgical castration) at Days 3, 7, and 14 following castration. More
      surgically castrated dogs required medical intervention than chemically castrated
      dogs (P=0.0328); the number of dogs requiring surgical repair within each group
      did not differ (P=0.3421). Seven chemically castrated dogs and 22 surgically
      castrated dogs experienced swelling, inflammation, and/or ulceration; all were
      managed medically. Two chemically castrated dogs experienced scrotal ulceration
      requiring surgical castration at Days 3 and 7. One surgically castrated dog
      experienced partial incisional dehiscence requiring surgical repair at Day 3. Our
      results suggest that chemical castration of dogs in field clinics is a feasible
      alternative to surgical castration, but proper follow-up care should be ensured
      for at least 7days post-procedurally.

PMID- 29183571
TI  - Echocardiographic and electrocardiographic parameters during the normal
      postpartum period in toy breeds of dogs.
AB  - The aim of this study was to evaluate echocardiographic and electrocardiographic
      parameters during the normal canine postpartum period. Twenty clinically healthy
      pregnant bitches of toy breeds (11 Miniature poodles, five Yorkshire terriers,
      two Maltese terriers and two Bichons Frises) were evaluated on days -3, 3, 10,
      17, 24, 38, 52 and 80 relative to parturition (day 0). During the first
      postpartum week, the width of the interventricular septum in systole, the
      shortening fraction and the left atrium size decreased, while the left ventricle
      internal diameter in systole and end systolic stress increased. There were
      progressive decreases in the velocity of circumferential fibre shortening, stroke
      volume, cardiac output, and mitral E and A wave values. Systolic blood pressure
      increased markedly during the first postpartum week to gradually increase
      thereafter. Heart rate and corrected QT interval progressively decreased, while P
      wave amplitude increased. QRS complex amplitude decreased in the second week
      after parturition and then increased during the following weeks. In conclusion,
      there were changes in systolic function and some structural adaptive changes in
      the bitch during the first 80days postpartum. In addition, maternal heart rate
      and corrected QT interval decreased, while P wave and QRS amplitudes increased.

PMID- 29183572
TI  - Evaluation of interferon-stimulated genes in peripheral blood granulocytes as
      sensitive responders to bovine early conceptus signals.
AB  - Early detection of gestation is important in the bovine industry. New methods
      have been developed to detect gene expression in leucocytes induced by interferon
      tau (IFNT) as gestation biomarkers. However, it is debatable which blood cell is
      suitable for detecting gene expression. This study was aimed at confirming
      whether granulocytes respond to IFNT specifically. Granulocytes and mononuclear
      cells (MNCs) from cows, and several types of bovine cultured cells, were treated
      with recombinant (r) IFNT and gene expression was analysed by quantitative real
      time reverse transcriptase (RT)-PCR and microarray analysis. Expression levels of
      IFN receptors (R1 and R2) were approximately 30- to 900-fold higher in
      granulocytes than in other cultured cells, and 1.5- to 2.5-fold higher in MNCs
      than in granulocytes. Microarray analysis following a 2h recombinant IFNT (rIFNT)
      treatment revealed expression changes for 900 genes in granulocytes. Genes with
      expression changes included known IFN-stimulated genes (ISGs; ISG15, OAS1, MX1,
      and MX2). Eighteen genes were selected following granulocyte microarray analysis
      and their expression changes were confirmed in early gestation, which revealed
      that nine genes had significantly higher expression levels in pregnant than in
      non-pregnant animals. In conclusion, granulocytes specifically responded to rIFNT
      treatment and the resulting gene expression changes correlated with those in
      vivo. Microarray analysis indicated that various genes showed expression changes
      in rIFNT-treated granulocytes, which may result in the identification of
      alternate candidate genes for the early detection of gestation. These results
      strongly indicate that gene expression in granulocytes is a suitable tool to
      determine pregnancy status.

PMID- 29183573
TI  - Age-dependent physiological dynamics in acid-base balance, electrolytes, and
      blood metabolites in growing goats.
AB  - There is a paucity of published data reporting acid-base equilibrium in goats,
      and no information is available on how the acid-base complexity changes when
      suckling goat kids become ruminants. The aims of this study were to evaluate
      young healthy goats for age-related changes in serum proteins, metabolites, and
      electrolytes; differences in results when the Henderson-Hasselbalch equation or
      strong ion approaches were used were also assessed. To assess biological
      variability and reproducibility, two consecutive long-term studies, each lasting
      from the 6th to 56th week of life (wl), were performed in 15 (Study 1) and 10
      (Study 2) animals. Blood gas analysis, serum biochemical analysis, and
      electrophoresis were performed on venous blood, and acid-base information was
      obtained using the traditional Henderson-Hasselbalch approach, Stewart's strong
      ion model, and Constable's simplified strong ion model. In all goats within the
      first 4-5 months, serum concentrations of glucose, l-lactate, and inorganic
      phosphate decreased significantly, while serum concentrations of total protein,
      albumin, and gamma globulin increased. Consequently, nonvolatile weak acids (Atot
      Alb and Atot TP) increased. At the end of this 'adaptation period', i.e. when
      milk was replaced by purely plant-based food, significantly lower bicarbonate and
      base excess values were accompanied by blood pH that shifted towards acidosis.
      Electrolytes (Na+, K+, Ca2+, and Cl-), anion gap, strong ion difference, and
      strong ion gap did not show age-dependent trends. In conclusion, somatic growth
      and development of gastro-intestinal fermentation in growing goats act as complex
      sources of physiological variability on acid-base equilibrium that was not
      reflected by the Henderson-Hasselbalch equation only.

PMID- 29183574
TI  - Assessment of a novel equine tarsocrural experimental joint disease model using
      recombinant interleukin-1beta and arthroscopic articular sampling of the medial
      malleolus of the tibia on the standing sedated horse.
AB  - Joint disease and osteoarthritis are common problems in the horse and numerous
      experimental studies have been developed to determine the safety and efficacy of
      new therapies. Synovitis, a critical component of joint disease, has been
      experimentally induced using recombinant interleukin-1 beta (reIL-1beta) to
      investigate new joint therapies in a controlled environment, although the use of
      reIL-1beta has not been reported in the equine tarsocrural joint. A common
      consequence of performing controlled experiments is that articular tissue
      collection typically requires general anesthesia or euthanasia. This report
      describes a minimally invasive surgical biopsy technique to harvest joint tissues
      from the tarsocrural joint in standing horses. The aims of the study were to
      assess subjective and objective pain parameters following reIL-1beta induced
      synovitis in the tarsocrural joint and to describe the surgical technique
      including the location and quantity of tissues obtained with this method.
      Experimental synovitis was induced using reIL-1beta in one equine tarsocrural
      joint of each horse using a randomised controlled design. The minimally invasive
      surgical technique provided sufficient amounts of articular cartilage from the
      medial malleolus of the tibia and synovium to perform viability, biochemical and
      histological assessments without necessitating general anesthesia. The minimally
      invasive technique also allowed for lameness assessment that could have been
      influenced by more invasive methods of tissue collection. No incisional or
      lameness complications were detected after use. The synovitis model and surgical
      technique provided ample tissue for laboratory evaluation and avoided general
      anesthesia or sacrifice of the horse.

PMID- 29183575
TI  - Diagnosis of canine pulmonary thromboembolism by computed tomography and
      mathematical modelling using haemostatic and inflammatory variables.
AB  - There is no evidence-based diagnostic approach for diagnosis of pulmonary
      thromboembolism (PTE) in dogs. Many dogs with diseases that predispose to
      thrombosis are hypercoagulable when assessed with thromboelastography (TEG), but
      no direct link has been established. The aims of this study were: (1) to
      investigate if diseased dogs with PTE, diagnosed by computed tomography pulmonary
      angiography (CTPA), had evidence of hypercoagulability by TEG; (2) to
      characterise haemostatic and inflammatory changes in dogs with PTE; (3) to
      construct models for prediction of PTE based on combinations of haemostatic and
      inflammatory variables; and (4) to evaluate the performance of D-dimer
      measurement for prediction of PTE. Twenty-five dogs were included in this
      prospective observational study (PTE: n=6; non-PTE: n=19). Clot strength G values
      did not differ between the PTE and non-PTE groups in tissue factor (TF) or kaolin
      activated TEG analyses. Haemostatic and inflammatory variables did not differ
      between the two groups. Linear discriminant analysis generated a model for
      prediction of PTE with a sensitivity and specificity of 100% when TF results were
      used as TEG data, and a model with sensitivity of 83% and specificity of 100%
      when kaolin results were used as TEG data. Receiver operating characteristic
      analysis of D-dimer levels showed that a value of >0.3mg/L yielded a sensitivity
      of 100% and a specificity of 71.4%. In conclusion, the study supports CTPA as
      method for diagnosing canine PTE, but shows that TEG alone cannot identify dogs
      with PTE. Models for prediction of PTE were generated, but require further
      validation.

PMID- 29183576
TI  - Geranium intoxication induces detoxification enzymes in the Japanese beetle,
      Popillia japonica Newman.
AB  - Popillia japonica is a generalist herbivore that feeds on >300 host plant species
      in at least 72 plant families. It is unknown why P. japonica, despite possessing
      active detoxification enzymes in its gut, is paralyzed when feeding on the petals
      of one of its preferred host plant, Pelargonium*hortorum, or on artificial diet
      containing quisqualic acid (QA), the active compound in zonal geranium. We
      hypothesized that Pelargonium*hortorum or QA do not induce activity of the
      cytochrome P450, glutathione S transferase (GST), and carboxylesterase (CoE)
      detoxification enzymes in P. japonica. In this study, P. japonica were fed petals
      of zonal geranium or agar plugs containing QA, or rose petals, another preferred
      but non-toxic host. Midgut enzyme activities of P450, GST, and CoE were then
      assayed after 6, 12, or 24h of feeding. In most cases, P450, GST, and CoE
      activities were significantly induced in P. japonica midguts by geranium petals
      and QA, though the induction was slower than with rose petals. Induced enzyme
      activity reached a peak at 24h after consumption, which coincides with the period
      of highest recovery from geranium and QA paralysis. This study shows that toxic
      geranium and QA induce detoxification enzyme activity, but the induced enzymes do
      not effectively protect P. japonica from paralysis by QA. Further investigation
      is required through in vitro studies to know if the enzymes induced by geranium
      are capable of metabolizing QA. This study highlights a rare physiological
      mismatch between the detoxification tool kit of a generalist and its preferred
      host.

PMID- 29183577
TI  - Identification and characterisation of seventeen glutathione S-transferase genes
      from the cabbage white butterfly Pieris rapae.
AB  - Insect glutathione S-transferases (GSTs) play essential roles in the
      detoxification of insecticides and other xenobiotic compounds. The cabbage white
      butterfly, Pieris rapae, is an economically important agricultural pest. In this
      study, 17 cDNA sequences encoding putative GSTs were identified in P. rapae. All
      cDNAs include a complete open reading frame and were designated PrGSTd1-PrGSTz2.
      Based on phylogenetic analysis, PrGSTs were divided into six classes (delta,
      epsilon, omega, sigma, theta and zeta). The exon-intron organizations of these
      PrGSTs were also analysed. Recombinant proteins of eight PrGSTs (PrGSTD1,
      PrGSTD2, PrGSTE1, PrGSTE2, PrGSTO1, PrGSTS1, PrGSTT1 and PrGSTZ1) were
      heterologously expressed in Escherichia coli, and all of these proteins displayed
      glutathione-conjugating activity towards 1-chloro-2,4-dinitrobenzene (CDNB).
      Expression patterns in various larval tissues, at different life stages, and
      following exposure to sublethal doses of abamectin, chlorantraniliprole or lambda
      cyhalothrin were determined by reverse transcription-quantitative PCR. The
      results showed that PrGSTe3, PrGSTs1, PrGSTs2, and PrGSTs4 were mainly
      transcribed in the fat body, while PrGSTe2 was expressed predominantly in the
      Malpighian tubules. Four genes (PrGSTe2, PrGSTo4, PrGSTs4 and PrGSTt1) were
      mainly expressed in fourth-instar larvae, while others were ubiquitously
      expressed in egg, larval, pupa and/or adult stages. Abamectin treatment
      significantly upregulated ten genes (PrGSTd1, PrGSTd3, PrGSTe1, PrGSTe2, PrGSTo1,
      PrGSTo3, PrGSTs1, PrGSTs3, PrGSTs4 and PrGSTt1). Chlorantraniliprole and lambda
      cyhalothrin treatment significantly upregulated nine genes (PrGSTd1, PrGSTd2,
      PrGSTe1, PrGSTe2, PrGSTe3, PrGSTs1, PrGSTs3, PrGSTs4 and PrGSTz1) and ten genes
      (PrGSTd1, PrGSTd3, PrGSTe1, PrGSTe2, PrGSTo1, PrGSTo2, PrGSTs1, PrGSTs2, PrGSTs3
      and PrGSTz2), respectively. These GSTs are potentially involved in the
      detoxification of insecticides.

PMID- 29183578
TI  - Molluscicidal activity and physiological toxicity of Macleaya cordata alkaloids
      components on snail Oncomelania hupensis.
AB  - In order to search new local plant molluscicides for the control of the vectors
      of schistosomiasis, leaves of Macleaya cordata (Willd) R. Br. were used to
      extract and separate alkaloid components by thinner acid method and column
      chromatography, and the molluscicidal effect of alkaloid components against snail
      Oncomelania hupensis was determined by bioassay. The results showed that 7
      alkaloid components (AN1-7) were obtained after extracting and separating
      alkaloids from the leaves of M. cordata, where AN2 was found being the most toxic
      against snail O. hupensis with 48h LC50 and LC90 values of AN2 of 6.35mg/L and
      121.23mg/L, respectively. Responses of some critical enzymes to AN2, including
      activities of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT),
      Aspartate transaminase (AST), Malic dehydrogenase (MDH) and Succinate
      dehydrogenase (SDH) in both cephalopodium and liver, were also detected through
      experiments, which also explored esterase isozyme (EST) exposed to AN2 in liver
      tissue. The results showed that AN2 significantly inhibited the activities of
      SDH, MDH and esterase isozyme, as AN2 significantly stimulated the activities of
      ALP, ALT and AST to increase at a low concentration (e.g. 25mg/L), while
      significantly inhibited the activities of these enzymes at a high concentration
      (100mg/L). These results indicated that AN2 not only inhibited protein synthesis,
      and respiratory chain oxidative phosphorylation, but also caused hepatocellular
      injury and reduced the detoxification ability of liver.

PMID- 29183579
TI  - Two novel house fly Vssc mutations, D600N and T929I, give rise to new insecticide
      resistance alleles.
AB  - The house fly, Musca domestica, is a serious pest because it transmits a large
      diversity of human and veterinary diseases. Insecticides, particularly
      pyrethroids, are commonly used to control house flies. However, the evolution of
      pyrethroid resistance has reduced the effectiveness of these insecticides. A
      major mechanism of resistance to pyrethroids is target site insensitivity caused
      by the mutations in the voltage-sensitive sodium channel (Vssc) gene (e.g. kdr
      [L1014F] and super-kdr [M918T+L1014F]). Recently, two novel Vssc alleles, super
      kdr+D600N and kdr+T929I were detected in a field collected resistant house fly
      population in Kansas, USA in 2013. To determine the levels of resistance that
      these new alleles confer to pyrethroids, we isolated strains having the unique
      Vssc alleles, but being otherwise congenic to the susceptible strain, aabys. We
      compared levels of resistance conferred to 14 pyrethroids and determined the
      inheritance of resistance to 8 pyrethroids. Our results revealed that super
      kdr+D600N conferred higher levels of resistance to seven pyrethroids relative to
      super-kdr, and kdr+T929I showed super-kdr-like levels of resistance in house
      flies. Our results are compared with previous studies and reveal that addition of
      T929I to the kdr mutation (L1014F) increased resistance to all pyrethroids
      (except etofenprox), and enhanced resistance by ~1000-fold to acrinathrin and
      flumethrin. The implications of these results on the evolution of resistance are
      discussed.

PMID- 29183580
TI  - Responses in reproductive organs, steroid hormones and CYP450 enzymes in female
      Mongolian gerbil (Meriones unguiculatus) over time after quinestrol treatment.
AB  - The aim of this study was to assess the effects and reversibility of the
      synthetic estrogen compound, quinestrol, on the reproductive organs, steroid
      hormones, and drug-metabolizing enzymes CYP3A4 and CYP1A2 in liver and kidney
      over time after two quinestrol treatments in female Mongolian gerbils (Meriones
      unguiculatus). Female gerbils were treated with 4mg/kg quinestrol (9
      gerbils/group, 3 treated group) (1 control group, 0mg/kg) for 3days and treated
      again after 25days. Animals were killed for collection of samples at 5, 10 and
      15days after the second treatment ending. Two interval quinestrol treatments
      significantly increased uterine weight, with trend of increase over time, but no
      change could be detected in ovarian weights. Quinestrol treatment increased
      progesterone and estradiol levels, both with trend of decline over time.
      Quinestrol increased liver and kidney weights and total enzyme content of CYP3A4
      and CYP1A2, with trend of decline over time. On the basis of reversible changes
      of detoxification enzymes or organs, interval quinestrol treatment effectively
      and reversibly influenced the reproductive hormone and organ to some extent.

PMID- 29183581
TI  - Deciphering the toxic effects of organochlorine pesticide, dicofol on human RBCs
      and lymphocytes.
AB  - Organochlorine pesticides have generated growing concern owing to their diverse
      toxicities. In this connection, we have evaluated toxic potential of an
      acaricide, dicofol (DCF) and its harmful effects on human RBCs and lymphocytes.
      DCF caused hemolysis and rupture of human erythrocytes as confirmed by scanning
      electron microscopy (SEM). Significant increase in protein oxidation, lipid
      peroxidation, ROS production, methemoglobin formation with enhanced activities of
      superoxide dismutase and catalase but decreased level of reduced glutathione were
      observed as a result of DCF exposure to human erythrocytes. SEM showed
      significant DCF induced alterations in RBCs from normal discoid shape to
      echinocytes. Similarly, lymphocytes showed membrane damage, formation of membrane
      blebs and distorted cell morphology. In vitro comet assay indicated a significant
      DNA fragmentation in human lymphocytes upon DCF exposure. These results strongly
      suggest that DCF induces oxidative stress in RBCs via generation of ROS and
      alters the cellular architecture directly and indirectly.

PMID- 29183582
TI  - Azadirachtin induced larval avoidance and antifeeding by disruption of food
      intake and digestive enzymes in Drosophila melanogaster (Diptera: Drosophilidae).
AB  - Botanical insecticides are a promising alternative to reduce the harmful effects
      of synthetic chemicals. Among the botanical biopesticides, azadirachtin obtained
      from the Indian neem tree Azadirachta indica A. Juss. (Meliaceae) is probably the
      biorational insecticide with greatest agriculture use nowadays due to its broad
      insecticide activity. The current study, evaluated the lethal and sublethal
      effects of azadirachtin on larval avoidance, food intake and digestive enzymes of
      Drosophila melanogaster larvae as biological model. Azadirachtin was applied
      topically at two doses LD25 (0.28MUg) and LD50 (0.67MUg) on early third instars
      larvae. Results evaluated 24h after treatment showed that larvae exhibited
      significant repellence to azadirachtin and prefer keeping in untreated arenas
      rather than moving to treated one. In addition, azadirachtin avoidance was more
      marked in larvae previously treated with this compound as compared with naif
      larvae (controls). Moreover, azadirachtin treatment decreased significantly the
      amount of larval food intake. Finally, azadirachtin reduced significantly the
      activity of larval alpha-amylase, chitinase and protease and increased the
      activity of lipase. This finding showed that azadirachtin induced behavioral and
      physiological disruption affecting the ability of the insect to digest food. This
      rapid installation of avoidance and long term antifeedancy might reinforce the
      action of azadirachtin and provide a new behavioral strategy for integrated pest
      management programs.

PMID- 29183583
TI  - The rescue of botanical insecticides: A bioinspiration for new niches and needs.
AB  - Crop protection is the basis of plant production and food security. Additionally,
      there are many efforts focused on increasing defensive mechanisms in order to
      avoid the damaging effects of insects, which still represent significant losses
      worldwide. Plants have naturally evolved different mechanisms to discourage
      herbivory, including chemical barriers such as the induction of defensive
      proteins and secondary metabolites, some of which have a historical link with bio
      farming practices and others that are yet to be used. In the context of global
      concern regarding health and environmental impacts, which has been translated
      into political action and restrictions on the use of synthetic pesticides, this
      review deals with a description of some historical commercial phytochemicals and
      promising proteinaceous compounds that plants may modulate to defeat insect
      attacks. We present a broader outlook on molecular structure and mechanisms of
      action while we discuss possible tools to achieve effective methods for the
      biological control of pests, either by the formulation of products or by the
      development of new plant varieties with enhanced chemical defenses.

PMID- 29183584
TI  - Inhibition of glucose-6-phosphate dehydrogenase protects hepatocytes from
      aluminum phosphide-induced toxicity.
AB  - Aluminum phosphide (AlP) poisoning is a severe toxicity with 30-70% mortality
      rate. However, several case reports presented AlP-poisoned patients with glucose
      6-phosphate dehydrogenase (G6PD) deficiency and extensive hemolysis who survived
      the toxicity. This brought to our mind that maybe G6PD deficiency could protect
      the patients from severe fatal poisoning by this pesticide. In this research, we
      investigated the protective effect of 6-aminonicotinamide (6-AN)- as a well
      established inhibitor of the NADP+- dependent enzyme 6-phosphogluconate
      dehydrogenase- on isolated rat hepatocytes in AlP poisoning. Hepatocytes were
      isolated by collagenase perfusion method and incubated into three different
      flasks: control, AlP, and 6-AN+ALP. Cellar parameters such as cell viability,
      reactive oxygen species (ROS) formation, mitochondria membrane potential collapse
      (MMP), lysosomal integrity, content of reduced (GSH) and oxidized glutathione
      (GSSG) and lipid peroxidation were assayed at intervals. All analyzed cellular
      parameters significantly decreased in the third group (6-AN+AlP) compared to the
      second group (AlP), showing the fact that G6PD deficiency induced by 6-AN had a
      significant protective effect on the hepatocytes. It was concluded that G6PD
      deficiency significantly reduced the hepatotoxicity of AlP. Future drugs with the
      power to induce such deficiency may be promising in treatment of AlP poisoning.

PMID- 29183585
TI  - Effects of the plant volatile trans-2-hexenal on the dispersal ability, nutrient
      metabolism and enzymatic activities of Bursaphelenchus xylophilus.
AB  - Bursaphelenchus xylophilus causes pine wilt disease (PWD), which severely damages
      pine species. The plant volatile trans-2-hexenal has strong activity against
      nematodes, although the precise mechanism of this inhibitory action remains
      unclear. In this paper, the fumigant effects of the LC10 and LC30 of trans-2
      hexenal on B. xylophilus were demonstrated. The trans-2-hexenal treatments
      significantly inhibited the dispersal ability of nematodes. The results also
      indicated that trans-2-hexenal affects the metabolism of nutrients and the
      activity of digestive enzymes. Among detoxifying enzymes, after treatment with
      trans-2-hexenal, glutathione S-transferase activity increased significantly and
      general esterase activity decreased significantly. Based on these results, trans
      2-hexenal disturbs the normal physiological and biochemical activities of this
      nematode. These results provide valuable insight into the nematicidal mechanisms
      of trans-2-hexenal.

PMID- 29183586
TI  - The protective effects of silybin on the cytotoxicity of thiram in human, rat and
      chicken cell cultures.
AB  - The study objective was a determination of thiram cytotoxicity and silybin
      cytoprotective activity in course of the fungicide impact on cell metabolism and
      membrane integrity. Firstly, human, rat, chicken hepatoma cells and rat myoblasts
      cultures were incubated with thiram. The results showed higher sensitivity of
      myoblasts on thiram exposure than the hepatoma cells. Among hepatoma cells, the
      chicken cultures were the most sensitive on the fungicide endangering. The
      mitochondrial activity was the most thiram affected function within all types the
      cell lines used. When silybin co-acted with thiram, an increase of the cell
      viability was recorded. The EC50-values were higher for thiram subjected to
      interaction with silybin than the effect of alone thiram action. The interaction
      mode between the studied compounds shown by combination index (CI) represented an
      antagonistic or an additive nature and was depended on thiram concentration, type
      of the cells and the assay used. Moreover, the morphology changes were dependent
      on silybin presence in the cell cultures subjected to thiram impact at the same
      time. Staining with Hoechst 33342 and propidium ioidium revealed the apoptosis
      cell death in the incubation cultures. Definitely, the results have shown a
      potential of silybin to protect the cultured cells in course of cytotoxicity
      induced by thiram. However, future studies taking into account other endpoints of
      thiram cytotoxicity pathways including species differences and the cytoprotection
      efficacy could be of interest.

PMID- 29183587
TI  - Comparison of subacute effects of two types of pyrethroid insecticides using
      metabolomics methods.
AB  - In this study, 1H NMR based metabolomics analysis, LC-MS/MS based serum
      metabolomics and histopathology techniques were used to investigate the toxic
      effects of subacute exposure to two types of pyrethroid insecticides bifenthrin
      and lambda-cyhalothrin in mice. Metabolomic analysis of tissues extracts and
      serum showed that these two types of pyrethroid insecticides resulted in
      alterations of metabolites in the liver, kidney and serum of mice. Based on the
      altered metabolites, several significant pathways were identified, which are
      associated with gut microbial metabolism, lipid metabolism, nucleotide
      catabolism, tyrosine metabolism and energy metabolism. The results showed that
      bifenthrin and lambda-cyhalothrin have similarities in disruption of metabolic
      pathways in kidney, indicating that the toxicological mechanisms of these two
      types of insecticides have some likeness to each other. This study may provide
      novel insight into revealing differences of toxicological mechanisms between
      these two types of pyrethroid insecticides.

PMID- 29183588
TI  - Heterologous formation of neonicotinoid-sensitive nAChRs containing UNC-38 and
      UNC-29 subunits from Bursaphelenchus xylophilus.
AB  - Nicotinic acetylcholine receptor (nAChR) subunits are encoded by a large
      multigene family and generate a large number of pentameric receptors with various
      properties. At present, nematode species, such as Caenorhabditis elegans, have
      the largest number of nAChR subunits. In this study, two nAChR subunits (Bxy-Unc
      38 and Bxy-Unc-29) were cloned from Bursaphelenchus xylophilus, a fatal nematode
      pest on pine trees causing pine wilt disease. When Bxy-Unc-38 and Bxy-Unc-29 were
      co-expressed in Xenopus oocytes, constructed functional nAChRs showed agonist
      responses to acetylcholine and imidacloprid, a neonicotinoid insecticide. When
      complementary RNAs (cRNAs) of Bxy-Unc-38 and Bxy-Unc-29 were injected at
      different ratios, the assembled nAChRs showed different pharmacological subtypes,
      especially in terms of the sensitivity to imidacloprid and another two
      neonicotinoids. At cRNA ratios 1:1 and 1:5 (Bxy-Unc-38: Bxy-Unc-29), nAChRs
      showed low sensitivity to test neonicotinoids, which were partial agonists on the
      receptors. In contrast, at cRNA ratio 5:1, the three test neonicotinoids were
      full agonists and showed much higher potency compared to that on the receptors
      with cRNA ratio 1:1 and 1:5. For example, EC50 values of the three neonicotinoids
      on the receptors with cRNA ratio 1:5 were 170-222 times of those of receptors
      with cRNA ratio 5:1. The results showed that the subunit stoichiometry of Bxy-Unc
      38/Bxy-Unc-29 receptor dramatically affected the agonist potency of
      neonicotinoids, and even altered the action property. Due to the high sensitivity
      of the constructed nAChRs at cRNA ratio 5:1, the construct would serve as an
      important model to study the interaction between invertebrate nAChRs and
      neonicotinoids.

PMID- 29183589
TI  - Novaluron ingestion causes larval lethality and inhibits chitin content in
      Leptinotarsa decemlineata fourth-instar larvae.
AB  - To accomplish consistent, long-term, integrated management (IPM) of the Colorado
      potato beetle, Leptinotarsa decemlineata (Say), research assessing the potential
      of novel, IPM-compatible insecticides is essential. Novaluron is a potent
      benzoylurea insecticide. In the present paper, we found that novaluron ingestion
      by the fourth-instar larvae inhibited foliage consumption, reduced larval fresh
      weight, and delayed development period, in a dose dependent manner. Most of the
      resulting larvae fail to pupate, and died at prepupae stage, with larvicidal
      activity comparable with those of cyhalothrin and spinosad but lower than those
      of fipronil and abamectin. Moreover, many surviving pupae that fed novaluron
      failed to emerge as adults, in a dose dependent pattern. Furthermore, feeding of
      novaluron significantly decreased chitin contents in body carcass (without
      midgut) and integument specimen, whereas the chitin concentration in the midgut
      peritrophic matrix was not affected. Furthermore, uridine diphosphate-N
      acetylglucosamine-pyrophosphorylase gene (LdUAP1) and chitin synthase Aa
      (LdChSAa), which were mainly responsible for chitin biosynthesis in ectodermally
      derived tissues, were surpressed and activated respectively after novaluron
      ingestion. Therefore, novaluron is an effective benzoylurea insecticide to L.
      decemlineata fourth-instar larvae. It inhibited chitin biosynthesis in
      ectodermally-derived tissues, disrupted ecdysis, impaired pupation and adult
      emergence, and led to death in juvenile life stages.

PMID- 29183591
TI  - Control efficiency and expressions of resistance genes in tomato plants treated
      with epsilon-poly-l-lysine against Botrytis cinerea.
AB  - The antifungal properties and the induction of resistance by epsilon-poly-l
      lysine (epsilon-PL) were examined to reveal its potential in protecting tomato
      plants against Botrytis cinerea. As presented herein, epsilon-PL at 1200mg/L was
      found to have optimal in vitro antifungal activities, achieving an inhibition
      rate of 94.96%. In first-year field tests, epsilon-PL (1200mg/L) had a control
      effect of up to 79.07% against tomato grey mould. Similar results were obtained
      in the second year. In greenhouse experiments, epsilon-PL was observed to
      effectively reduce leaf infection, with an observed control rate at 89.22%. To
      define the molecular-genetic mechanisms, we compared the gene expression under
      four different conditions: sterile water sprayed plants (Control), Botrytis
      infected plants (Inf), epsilon-PL-treated plants (epsilon-PL) and epsilon-PL
      treated+infected plants (epsilon-PL+Inf). Quantitative PCR analysis at 36h after
      inoculation revealed that epsilon-PL+Inf plants exhibited significant expression
      and priming of several key Botrytis-induced genes in tomato. The results indicate
      that epsilon-PL promoted plant capacity of tomato to activate defense mechanisms
      upon pathogen attack. In total, these findings revealed that epsilon-PL should be
      an excellent biocontrol agent candidate that combined direct antifungal activity
      against B. cinerea and plant resistance capacity.

PMID- 29183592
TI  - Preface to the Special Issue: Herbicide Toxicology in China.

PMID- 29183590
TI  - Genetic mutations in sodium channel domain II and carboxylesterase genes
      associated with phenotypic resistance against synthetic pyrethroids by
      Rhipicephalus (Boophilus) decoloratus ticks in Uganda.
AB  - We previously reported emergence of super synthetic pyrethroid (SP) resistant
      Rhipicephalus (Boophilus) decoloratus ticks in Uganda. This study investigated
      the genetic basis of phenotypic resistance against SP in R. (B.) decoloratus and
      sought to identify novel diagnostic mutations for rapid detection of SP
      resistance in the above tick species. Genomic DNA was extracted from pooled
      larvae of 20 tick populations (19 of known SP susceptibility and 1 unknown
      susceptibility). The voltage sensitive sodium channel (VSSC) domain II S4-5
      linker (SP target) and partial carboxylesterase (SP metabolizing enzyme) genes
      were amplified by PCR, cloned and sequenced. The resultant sequences were
      analyzed to determine single nucleotide polymorphisms (SNPs) associated with
      phenotypic resistance in the various tick populations investigated. Novel SNPs
      that introduced Eco RI and Eco RII restriction sites in carboxylesterase gene
      were identified in silco and validated with restriction fragment length
      polymorphism (RFLP) against 18 tick populations of known SP susceptibility. The
      study identified a super knock down resistance (kdr) mutation T58C in R. (B.)
      decoloratus VSSC associated with stable SP resistance. We further identified
      multiple nonsynonymous mutations in carboxylesterase of SP resistant ticks; one
      of which conferred novel EcoRII (G195C) restriction site for PCR-RFLP detection
      of SP resistance. In conclusion, this study is the first to report super kdr
      mutation in sodium channel domain II and multiple mutations in carboxylesterase
      genes that may concurrently mediate stable resistance against synthetic
      pyrethroids in R. (B.) decoloratus ticks from Uganda. The Eco RII based PCR-RFLP
      is a useful tool for rapid detection of stable SP resistant R. (B.) decoloratus
      ticks.

PMID- 29183593
TI  - Characterization of Eleusine indica with gene mutation or amplification in EPSPS
      to glyphosate.
AB  - The evolution of weed-resistant species threatens the sustainable use of
      glyphosate, which is the most important herbicide widely used in agriculture
      worldwide. Moreover, the high glyphosate resistance (>180-fold based on LD50) of
      Eleusine indica found in Malaysia, which carries a double mutation in its 5
      enolpyruvylshikimate-3-phosphate synthase (EPSPS), made the control of this
      species more difficult. By contrast, the same species carrying the same double
      mutation in EPSPS (T102I+P106S) but found in China only shows a resistance level
      of not more than 14-fold based on GR50. The resistance level of this population
      is four times higher than that of the population carrying a single mutation
      (P106L). Although the members of this population survive under a high glyphosate
      dosage of 10,080gaeha-1, their growth was significantly inhibited by glyphosate
      under the recommend dose (840gaeha-1), where in the fresh weight was 85.4% of the
      control. EPSPS expression, relative copy number, and EPSPS activity in this
      population were similar to those of the susceptible population. In addition, the
      expression of two glutathione transferase (GST) genes (GST-U8 and GST-23) and the
      enzyme activity of the GST in this population did not significantly differ from
      those of the susceptible population. This finding is important in elucidating the
      resistance of the naturally evolved glyphosate-resistant (GR) weed species
      carrying a double mutation in EPSPS to glyphosate.

PMID- 29183594
TI  - The distribution and species of Ca2+ and subcellular localization of Ca2+ and
      Ca2+-ATPase in grape leaves of plants treated with fluoroglycofen.
AB  - Fluoroglycofen, a post-emergence herbicide used in vineyards to eradicate weeds,
      has previously been shown to turn grape leaves dark green following its use.
      Therefore, this study evaluates the relationship of dark green leaves with
      calcium form and subcellular distribution. To do this, we focused on the Ca2+
      distribution and Ca2+-ATPase activity in leaf cells of one-year-old self-rooted
      Chardonnay grapevines treated with fluoroglycofen. Plants were separated into
      different treatments when they had seven or eight leaves, and different
      concentrations of fluoroglycofen were sprayed on the sand. The results showed
      that all of the soluble calcium content in the grape leaves that were treated
      with the highest concentration of fluoroglycofen (187.5gaiha-1) increased
      significantly. Specifically, the water-soluble organic acid calcium, pectate
      calcium, and calcium oxalate increased by 18.43%, 17.14%, and 31.05%,
      respectively, in the upper leaves than in the control. The subcellular
      distribution of Ca2+ in the dark green leaves increased significantly, especially
      in the cell wall and chloroplast, which increased by 25.54% and 24.10%,
      respectively. Through the ultrastructure localization of Ca2+ and Ca2+-ATPase
      contrasted with the control, the extracellular space and chloroplasts in the
      mesophyll cells of dark green leaves had large calcium pyroantimonate (Ca-PA)
      deposits. The extracellular space had fewer Ca2+-ATPase precipitation particles,
      whereas the chloroplasts had more. At the same time, a high concentration of
      fluoroglycofen decreased Ca2+-ATPase activity in grape leaves, which potentially
      might be due to disrupted regulation of calcium homeostatic mechanisms inside and
      outside of cells, resulting in a large number of Ca2+ accumulation in cells. The
      Ca2+ accumulation not only hindered the various cellular physiological reactions,
      but also caused leaves to become dark green in color.

PMID- 29183595
TI  - Interactions between salicylic acid and antioxidant enzymes tilting the balance
      of H2O2 from photorespiration in non-target crops under halosulfuron-methyl
      stress.
AB  - Halosulfuron-methyl (HSM) is a safe, selective and effective sulfonylurea
      herbicide (SU) for the control of sedge and broadleaf weeds in sugarcane, corn,
      tomato, and other crops. The primary site of action is acetolactate synthase
      (ALS), a key enzyme of branched chain amino acids (BCAAs) synthesis. In addition
      to ALS inhibition, BCAAs deficiencies and oxidative damage may be involved in
      toxic effects of SUs. However, secondary targets of HSM relevant to plant
      physiological responses are unclear. In the present study, comparative growth
      inhibition and peroxidization injury between sensitive and tolerance crops were
      observed at biochemical and physiological levels suggesting involvement of H2O2,
      ethylene, salicylic acid (SA) in the oxidative stress responses to HSM. HSM
      caused accumulation of H2O2, stimulated photorespiration and consequent
      accumulation of SA that worsened the peroxidization injury to the sensitive C3
      plant soybean (Glycine max). The growth inhibition at low concentrations of HSM
      could be lessened by supplementary BCAAs, reactive oxygen species scavengers or
      ethylene inducers, whereas the oxidation damage at high concentrations of HSM
      could not be reversed and ultimately lead to plant death. H2O2 at a low level
      stimulated the antioxidase system including glutathione S-transferase activities
      in the HSM-tolerant C4 maize (Zea mays), which contributes to HSM tolerance. H2O2
      plays an important role on HSM stress responses in both HSM-sensitive and HSM
      tolerant soybean and maize.

PMID- 29183596
TI  - Effect of allelochemical tricin and its related benzothiazine derivative on
      photosynthetic performance of herbicide-resistant barnyardgrass.
AB  - Despite increasing knowledge of allelochemicals as leads for new herbicides,
      relatively little is known about the mode of action of allelochemical-based
      herbicides on herbicide-resistant weeds. In this study, herbicidal activities of
      a series of allelochemical tricin-derived compounds were evaluated. Subsequently,
      a benzothiazine derivative 3-(2-chloro-4-methanesulfonyl)-benzoyl-hydroxy-2
      methyl-2H-1,2-benzothiazine-1,1-dioxide with 4-hydroxyphenyl-pyruvate dioxygenase
      (HPPD) inhibiting activity was identified as a target compound on photosynthetic
      performance of penoxsulam-resistant versus -susceptible barnyardgrass
      (Echinochloa crus-galli). Regardless of barnyardgrass biotype, the benzothiazine
      derivative greatly affected chlorophyll fluorescence parameters (Fv/Fm, ETR1min
      and NPQ1min), reduced the chloroplast fluorescence levels and expression of HPPD
      gene. In particular, the benzothiazine derivative interfered with photosynthetic
      performance of resistant barnyardgrass more effectively than the allelochemical
      tricin itself. These results showed that the benzothiazine derivative effectively
      inhibited the growth of resistant barnyardgrass and its mode of action on
      photosynthesis system was similar to HPPD-inhibiting sulcotrione, making it an
      ideal lead compound for further development of allelochemical-based herbicide
      discovery.

PMID- 29183597
TI  - Resistance to quinclorac caused by the enhanced ability to detoxify cyanide and
      its molecular mechanism in Echinochloa crus-galli var. zelayensis.
AB  - Quinclorac, an auxin-type herbicide, is widely used to control barnyardgrass and
      some dicotyledon weeds. Echinochloa crus-galli var. zelayensis, a variety of E.
      crus-galli (L.) Beauv., is widespread in China and some populations have
      resistance to quinclorac. E. crus-galli var. zelayensis seeds with varying
      sensitivity to quinclorac were used in the present study. The expression of the
      ADP/ATP carrier protein (ANT) gene, which plays an important role in the
      maintenance of cellular energy balance, dramatically rose in the S biotype after
      exposure to quinclorac, while no change was found in two R biotypes. The activity
      of beta-cyanoalanine synthase (beta-CAS), which is the key enzyme for cyanide
      degradation, was higher in two R biotypes than in the S biotype before and after
      treatment with quinclorac. One single-nucleotide difference was detected in the
      EcCAS gene of two R biotypes compared with the S biotype. The nucleotide change,
      which caused one amino acid substitution, replacing Methionine (Met)-295 with
      Lysine (Lys)-295 in the two R biotypes, which are same as the rice beta-CAS gene
      at this position. In addition, EcCAS gene expression was higher in the two R
      biotypes than in the S biotype. In conclusion, beta-CAS may play a crucial role
      in the resistance of E. crus-galli var. zelayensis to quinclorac. EcCAS gene
      mutation and higher gene expression may enhance the activity of beta-CAS to avoid
      the accumulation of toxic cyanide in resistant populations, thus contributing to
      the resistance mechanism of E. crus-galli var. zelayensis. to quinclorac.

PMID- 29183598
TI  - Tribenuron-methyl resistance and mutation diversity of the AHAS gene in
      shepherd's purse (Capsella bursa-pastoris (L.) Medik.) in Henan Province, China.
AB  - Shepherd's purse is a troublesome dicot weed that occurs in the major wheat
      producing areas in China. Twenty-eight shepherd's purse populations were
      collected from winter wheat-planting areas in Henan Province and used to evaluate
      tribenuron-methyl resistance and acetohydroxyacid synthase (AHAS) gene-mutation
      diversity. The results indicate that all 28 shepherd's purse populations were
      resistant to tribenuron-methyl at different levels compared with the susceptible
      population. Mutation of the 197 codon (CCT) changed proline (Pro) into tyrosine
      (Tyr), histidine (His), leucine (Leu), serine (Ser), arginine (Arg), alanine
      (Ala) and threonine (Thr), whereas mutation of the 574 codon (TGG) changed
      tryptophan (Trp) into leucine (Leu). Among these amino acid changes, a co
      concurrence of Pro197Leu and Trp574Leu substitutions was identified for the first
      time in resistant weed species. Furthermore, Pro197Tyr, Pro197Arg and Pro197Ala
      substitutions have not been previously reported in shepherd's purse. The results
      of the in vitro AHAS assay suggest that an insensitive AHAS is likely involved in
      the resistance to tribenuron-methyl in the R populations with AHAS gene
      mutations, and the non-target-site based resistance might exist in some
      populations.

PMID- 29183599
TI  - Design, synthesis, and herbicidal activity of novel quaternary ammonium salt
      derivatives.
AB  - A series of novel quaternary ammonium salt derivatives were designed and
      synthesized by introducing the herbicide carboxylic acid into substituted
      aminoacetanilide compounds which derived from herbicides alachlor or acetochlor,
      using the intermediate derivatization methods in an attempt to obtain novel
      candidates for weed control. The herbicidal activity assays in greenhouse
      demonstrated that some of the title compounds exhibited good herbicidal
      activities against velvet leaf, youth-and-old age, barnyard grass, and foxtail.
      Especially, III9 gave the best activity (EC50 (ga.i/ha): YOA 34.1, VEL 33.6, FOX
      15.9, BYG 36.2). The field trials indicated that III9 had better herbicidal
      activity than the commercial herbicide imazethapyr to control broadleaf weeds at
      150ga.i/ha. The present work demonstrated that the quaternary ammonium salt
      derivatives can be used as potential lead compounds for discovering novel
      herbicides with improved activity. III9 itself is worthy of being further
      developed as an herbicidal candidate. Further syntheses, structure optimization
      studies, and field trials around III9 are in progress.

PMID- 29183600
TI  - Recent advances in tenuazonic acid as a potential herbicide.
AB  - Tenuazonic acid (TeA), belonging to tetramic acids that are the largest family of
      natural products, is a mycotoxin produced by members of the genus Alternaria and
      other phytopathogenic fungi. TeA has many desirable bioactivities. In the past
      two decades, several studies have addressed its phytotoxic activity. Because it
      can cause brown leaf spot and kill seedlings of mono- and dicotyledonous plants,
      TeA is regarded as a potential herbicidal agent. TeA blocks electron transport
      beyond QA by interacting with D1 protein and is a PSII inhibitor. The chloroplast
      derived oxidative burst is responsible for TeA-induced cell death and plant
      necrosis. Based on the model of molecular interaction between TeA and D1 protein,
      a series of its derivatives with stable herbicidal activity have been designed,
      evaluated and patented. Recently, some chemical synthetic approaches of TeA and
      its derivatives have been successfully developed. This paper will mainly focus on
      new developments regarding TeA's herbicidal activity, mode of action,
      biosynthesis and chemical synthesis, and characterization of new derivatives.

PMID- 29183601
TI  - Involvement of H2O2 in fluazifop-P-butyl-induced cell death in bristly starbur
      seedlings.
AB  - In order to understand the action mechanism of fluazifop-P-butyl (FB) in bristly
      starbur (Acanthospermum hispidum D.C.), a susceptible plant, the role of active
      oxygen species (ROS) in herbicide-induced cell death in shoots was investigated.
      FB-induced phytotoxicity was not reduced by the antioxidants, 1,4
      diazabicyclooctane (dabaco), sodium azide, l-tryptophan, d-tryptophan,
      hydroquinone and dimethyl pyridine N-oxide (DMPO). The activities of superoxide
      dismutase (SOD) and catalase (CAT), in bristly starbur seedlings were
      significantly increased by FB at 12 HAT and 24 HAT, while ascorbate peroxidase
      (APX) and glutathione reductase (GR) activities increased only at 12 HAT. The
      contents of H2O2 in FB-treated bristly starbur seedlings were significantly
      higher to that of control between 8 and 24 HAT. According to the analysis of
      potassium iodide - starch or 3,3-diaminobenzidine, the accumulation of hydrogen
      peroxide was observed in the apical growing point, stem, petiole and veins of FB
      treated bristly starbur seedlings at 24 HAT. The cell viability of bristly
      starbur seedlings treated by 10MUM FB decreased at 18 HAT. These results
      suggested that FB-induced cell death in bristly starbur shoots may be caused by
      ROS (O2- and H2O2) generation and lipid peroxidation.

PMID- 29183602
TI  - Copper complexes of the 1,3,4-thiadiazole derivatives modulate antioxidant
      defense responses and resistance in tomato plants against fungal and bacterial
      diseases.
AB  - The metallic complexes MU-chloro-MU-[2,5-bis (2-pyridyl)-1,3,4-thiadiazole] aqua
      chlorocopper (II) dichlorocopper (II) (abbreviated 2PTH-Cu2-Cl4); aquabis [2,5
      bis (2-pyridyl)-1,3,4-thiadiazole-kappa2N2,N3] (trifluoromethane-sulfonato
      kappaO) copper(II) trifluoro metrhanesulfonate (2PTH-Cu-tF) and bis[(2,5
      bis(pyridine-2-yl)-1,3,4-thiadiazole-di-azido copper(II)] (2PTH-Cu-Az) were
      compared for their antimicrobial activities in vitro, and their aptitude to
      control Verticillium wilt and crown gall diseases development of tomato in the
      greenhouse. Results showed that the complex 2PTH-Cu-Az inhibited drastically the
      growth of V. dahliae in vitro. 2PTH-Cu2-Cl4 and 2PTH-Cu-tF did not display any
      noticeable antimicrobial activity in vitro against all of the pathogens tested.
      However, in planta evaluation revealed that the three complexes protected tomato
      against crown gall similarly. They also reduced Verticillium wilt disease
      severity, although the complex 2PTH-Cu-Az was the most efficient. When compared
      to other complexes, 2PTH-Cu-Az triggered only a weak oxidative burst as revealed
      by H2O2 measurement and the activity of ascorbate peroxidase and catalase. These
      results suggest that the superiority of 2PTH-Cu-Az against V. dahliae rely on its
      direct antifungal activity and its ability to modulate H2O2 accumulation.

PMID- 29183603
TI  - Characterization of glutathione S-transferases in the detoxification of
      metolachlor in two maize cultivars of differing herbicide tolerance.
AB  - Glutathione S-transferases (GSTs) have been widely studied in relation to their
      role in herbicide tolerance and detoxification. However, a detailed
      characterization of GSTs from herbicide tolerant and sensitive maize cultivars is
      still lacking. In this study, we determined the mechanism of differential
      tolerance between two maize cultivars which had 4-fold difference tolerance to
      metolachlor. The metabolism rate of metolachlor was more rapid in the tolerant
      cultivar (Zea mays L. cv Nongda86) than the susceptible one (Zea mays L. cv
      Zhengda958). Addition of the GST inhibitor ethacrynic acid reduced the metabolism
      of metolachlor indicating the involvement of GSTs in the differential
      detoxification of metolachlor. The expression profiles of 32 GST isozymes were
      measured using quantitative RT-PCR. The results showed the expression of GST
      genes were slightly up-regulated in Nongda86, but severely inhibited in
      Zhengdan958 24h after metolachlor treatment. The genes GSTI, GSTIII, GSTIV, GST5,
      GST6 and GST7, which can detoxify chloroacetanilide herbicides, were all
      expressed higher in Nongda86 compared to Zhendgan958. The result of GST activity
      was consistent with the gene expression profiles. Collectively, higher-level
      expression of GST genes, leading to higher GST activity and faster herbicide
      detoxification, appears to be responsible for the difference in tolerance to
      metolachlor in two maize cultivars.

PMID- 29183604
TI  - Microbial catabolism of chemical herbicides: Microbial resources, metabolic
      pathways and catabolic genes.
AB  - Chemical herbicides are widely used to control weeds and are frequently detected
      as contaminants in the environment. Due to their toxicity, the environmental fate
      of herbicides is of great concern. Microbial catabolism is considered the major
      pathway for the dissipation of herbicides in the environment. In recent decades,
      there have been an increasing number of reports on the catabolism of various
      herbicides by microorganisms. This review presents an overview of the recent
      advances in the microbial catabolism of various herbicides, including
      phenoxyacetic acid, chlorinated benzoic acid, diphenyl ether, tetra-substituted
      benzene, sulfonamide, imidazolinone, aryloxyphenoxypropionate, phenylurea,
      dinitroaniline, s-triazine, chloroacetanilide, organophosphorus, thiocarbamate,
      trazinone, triketone, pyrimidinylthiobenzoate, benzonitrile, isoxazole and
      bipyridinium herbicides. This review highlights the microbial resources that are
      capable of catabolizing these herbicides and the mechanisms involved in the
      catabolism. Furthermore, the application of herbicide-degrading strains to clean
      up herbicide-contaminated sites and the construction of genetically modified
      herbicide-resistant crops are discussed.

PMID- 29183605
TI  - Synthesis and herbicidal activity of optically active alpha-(substituted
      phenoxyacetoxy) (substituted phenyl) methylphosphonates.
AB  - alpha-(Substituted phenoxyacetoxy) alkylphosphonates containing one chiral carbon
      atom have been demonstrated to be PDHc inhibitor with good herbicidal activity
      and some of them could be used as potential herbicide. In order to determine any
      difference in herbicidal activities between (R) and (S) isomers, the synthetic
      method of optically active substituted phenylalkylphosphonates IB were explored.
      A highly practical, enantioselective hydrophosphonylation was developed to
      prepare optically active O,O-dimethyl alpha-hydroxyalkylphosphonates 3 as key
      intermediate by asymmetric addition reaction of dimethylphosphite 1 and several
      kinds of aldehydes 2 using tridentate Schiff base Al(III) complexes as catalysts.
      A series of novel O,O-dimethyl alpha-(substituted phenoxyacetoxy)(substituted
      phenyl)methylphosphonates IB including (R) and (S) enantiomers were further
      synthesized with excellent enantioselectivity (95-99% ee) by the condensation of
      optically active alpha-hydroxyl (substituted phenyl)methylphosphonates 3 and
      substituted phenoxyacetyl chlorides 4. The herbicidal activities of title
      compound IB including their racemates, (R) and (S) enantiomers were evaluated in
      greenhouse for post-emergence application. All compounds IB showed significant
      inhibitory activity against dicotyledonous plants. A difference in herbicidal
      effect among racemate, (R) and (S) enantiomers were observed. Especially IB7 and
      IB10 showed obvious chiral selectivity in inhibitory activity against chickweed.
      (S)-IB7 with ED50 of 22.8gai/ha was found to be most effective enantiomer against
      chickweed and its inhibitory activity was 8.17 times higher than (R)-IB7. (S)-IB7
      as potential herbicide would be effective at lower rates than (R)-IB7 or (rac)
      IB7.

PMID- 29183606
TI  - Mechanism of resistance to cyhalofop-butyl in Chinese sprangletop (Leptochloa
      chinensis (L.) Nees).
AB  - Chinese sprangletop (Leptochloa chinensis (L.) Nees) is a serious grass weed in
      rice paddies. In some areas, L. chinensis has become resistant to the herbicide
      cyhalofop-butyl because of its frequent and extensive use over the past five
      years. In this study, whole-plant dose-response assays were conducted, and a L.
      chinensis population (ZHYH) had a 75.8-fold resistance index to cyhalofop-butyl.
      Molecular analyses revealed that this resistance was attributed to a tryptophan
      (Trp)-2027-to-cysteine (Cys) substitution in the CT domain of the ACCase gene. To
      our knowledge, this is the first report revealing the mechanism underlying
      cyhalofop-butyl resistance in L. chinensis. Furthermore, a derived cleaved
      amplified polymorphic (dCAPS) assay was developed to rapidly detect the Trp-2027
      Cys mutation. Of the 100 ZHYH plants analyzed, 52 were heterozygous mutants and
      48 were susceptible homozygous plants. In addition, the cyhalofop-butyl-resistant
      L. chinensis was cross-resistant to aryloxyphenoxypropionate and phenylpyrazoline
      herbicides, but not to cyclohexanedione, acetolactate synthase-inhibiting,
      protoporphyrinogen oxidase, and urea herbicides, and had only slight resistance
      to the hormonal herbicide quinclorac.

PMID- 29183607
TI  - Fluazifop-P-butyl induced ROS generation with IAA (indole-3-acetic acid)
      oxidation in Acanthospermum hispidum D.C.
AB  - Acanthospermum hispidum D.C. was particularly susceptible to fluazifop-P-butyl,
      an aryloxyphenoxypropionate herbicide, and the primary action site for the
      herbicide was shoot apical meristem, which is also the main site of indole-3
      acetic acid (IAA) biosynthesis and action. Membrane lipid peroxidation caused by
      increasing levels of reactive oxygen species (ROS) was considered as an action
      mechanism of fluazifop-P-butyl in A. hispidum. To further clarify the ROS
      inducing mechanism of fluazifop-P-butyl in the plant, the interactions between
      fluazifop-P-butyl and auxin compounds IAA or 2,4-dichlorophenoxyacetic acid (2,4
      D) were studied. Haloxyfop-P-methyl, an AOPP herbicide which is inactive on A.
      hispidum, was used for comparison. The results showed that the growth inhibition
      and malondialdehyde or H2O2 increases induced by fluazifop-P-butyl on A. hispidum
      were reversed by IAA or 2,4-D. The IAA content was decreased but the contents of
      three IAA oxidation metabolites, indole-3-methanol, indole-3-aldehyde and indole
      3-carboxylic acid were increased by fluazifop-P-butyl in A. hispidum, but not by
      haloxyfop-P-methyl. The growth of A. hispidum was not inhibited by three IAA
      oxidative compounds. Moreover, the activities of IAA oxidase and peroxidase were
      increased by fluazifop-P-butyl but not by haloxyfop-P-methyl, and the increase
      was reversed by IAA or 2,4-D. We suggest that there is an antagonistic effect
      between fluazifop-P-butyl and IAA or 2,4-D, and the IAA oxidation may be involved
      in the action mechanism of fluazifop-P-butyl in A. hispidum.

PMID- 29183608
TI  - N'-mono- and N, N'-diacyl derivatives of benzyl and arylhydrazines as contact
      insecticides against adult Anopheles gambiae.
AB  - New public health insecticides are urgently required to prevent the spread of
      vector-borne disease. With the goal of identifying new K+-channel-directed
      mosquitocides, analogs of the RH-5849 family of diacyl t-butylhydrazines were
      synthesized and tested for topical toxicity against adult Anopheles gambiae, the
      African vector of malaria. In total, 80N'-monoacyl and N, N'-diacyl derivatives
      of benzyl- and arylhydrazines were prepared. Three compounds (2bo, 2kb, 3ab) were
      identified that were more toxic than RH-5849 and RH-1266. The potencies of these
      compounds to block K+ currents in An. gambiae and human Kv2.1 channels were
      assessed to address their possible mechanism of mosquitocidal action. Selectivity
      for inhibition of An. gambiae Kv2.1 vs human Kv2.1 did not exceed 3-fold.
      Furthermore, no correlation was seen between the potency of insecticidal action
      and K+ channel blocking potency. These observations, combined with the minimal
      knockdown seen with 2bo near its LD50 value, suggests a mode of action outside of
      the nervous system.

PMID- 29183609
TI  - Monitoring insecticide resistance and diagnostics of resistance mechanisms in the
      green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae) in China.
AB  - Myzus persicae (Sulzer) is one of the most serious agricultural pests in China,
      and management strategies mainly rely on insecticidal treatment. To evaluate the
      resistance of field populations of M. persicae to seven insecticides, we assessed
      the susceptibility of 11 field populations collected from eight provinces in
      China using leaf-dip bioassays. Toxicity assays showed that M. persicae field
      populations have developed several levels of resistance to each tested
      insecticide. For pyrethroids, the field populations have developed a high level
      of resistance to beta-cypermethrin and cypermethrin, while the resistance to
      bifenthrin is still low. The resistance ratios of field populations to
      imidacloprid ranged from 1.48 to 52.36, and eight populations have developed
      moderate to high resistance. Resistance to acetamiprid is low, and only two
      populations have a moderate level of resistance. Most of the field populations of
      M. persicae developed moderate to high resistance to methomyl and omethoate. To
      investigate potential resistance mechanisms, we analyzed the enzyme activity of
      carboxylesterases, the type of amplified esterase genes, as well as the kdr
      (L1014F) mutation. All of the field populations exhibited a higher esterase
      activity compared to the laboratory susceptible strain. An amplified FE4, as well
      as the L1014F mutation, were also found in all of our experimental field
      populations. These results provide valuable insight into the current status of
      insecticide resistance and will prove to be a valuable resource in designing
      appropriate resistance management strategies for M. persicae in China.

PMID- 29183610
TI  - Chlorine dioxide enhances lipid peroxidation through inhibiting calcium
      independent cellular PLA2 in larvae of the Indianmeal moth, Plodia
      interpunctella.
AB  - Polyunsaturated fatty acids usually undergo lipid peroxidation induced by
      reactive oxygen species (ROS). Calcium-independent cellular phospholipase A2
      (iPLA2) can maintain fatty acid compositions in phospholipids depending on
      physiological conditions. An insect iPLA2 (Pi-iPLA2) was predicted from the
      transciptome of the Indianmeal moth, Plodia interpunctella. It encodes 835 amino
      acids. It possesses five ankyrin repeats in the N terminal and patatin lipase
      domain in the C terminal. Pi-iPLA2 was expressed in all developmental stages of
      the Indianmeal moth. In the larval stage, it was expressed in all tissues tested.
      RNA interference (RNAi) specific to Pi-iPLA2 was performed using specific double
      stranded RNA (dsRNA). It resulted in almost 70% of reduction in gene expression.
      Under such RNAi condition, P. interpunctella exhibited significant accumulation
      of lipid peroxidation based on the amount of malondialdehyde. RNAi of Pi-PLA2
      expression also impaired cellular immune response of P. interpunctella. Chlorine
      dioxide (ClO2), an insecticidal agent by generating ROS, increased lipid
      peroxidation in a dose-dependent manner. However, the addition of vitamin E (an
      antioxidant) reduced the formation of lipid peroxidation. ClO2 treatment
      significantly reduced expression of Pi-iPLA2 but increased lipid peroxidation in
      larval fat body of P. interpunctella. Furthermore, larvae treated with dsRNA
      specific to Pi-iPLA2 were significantly susceptible to ClO2 treatment. These
      results suggest that Pi-iPLA2 plays a crucial role in repairing damaged fatty
      acids from phospholipids. Our results also suggest that ClO2 can elevate lipid
      peroxidation through inhibiting Pi-iPLA2 expression in addition to direct ROS
      production.

PMID- 29183611
TI  - The R81T mutation in the nicotinic acetylcholine receptor of Aphis gossypii is
      associated with neonicotinoid insecticide resistance with differential effects
      for cyano- and nitro-substituted neonicotinoids.
AB  - The cotton aphid, Aphis gossypii Glover, is one of the most agriculturally
      important insect pests. Neonicotinoid insecticides and sulfoxaflor have generally
      shown excellent control of A. gossypii, but these aphids have recently developed
      resistance against neonicotinoid insecticides. We previously characterized a
      field-collected A. gossypii Kushima clone that showed higher resistance to nitro
      substituted neonicotinoids, such as imidacloprid, than to cyano-substituted
      neonicotinoids, such as acetamiprid. This Kushima clone harbors the R81T mutation
      in the nicotinic acetylcholine receptor (nAChR) beta1 subunit; this mutation is
      the source of neonicotinoid insecticide resistance. In the present study,
      electrophysiological analyses and molecular modeling were employed to investigate
      the differential effects of the R81T mutation on cyano- and nitro-substituted
      neonicotinoids and sulfoxaflor. We isolated full-length coding sequences of A.
      gossypii nAChR alpha1, alpha2, and beta1 subunits. When co-expressed in Xenopus
      laevis oocytes with chicken beta2 nAChR, A. gossypii alpha1 evoked inward
      currents in a concentration-dependent manner in response to acetylcholine (ACh)
      and showed sensitivity to neonicotinoid and sulfoxaflor. Additionally, the
      chicken beta2 T77R+E79V (equivalent double mutant of R81T) mutation resulted in a
      lower effect to cyano-substituted neonicotinoids and sulfoxaflor than to nitro
      substituted neonicotinoids. Electrophysiological data and nAChR homology modeling
      analysis suggested that the Kushima clone exhibited different levels of
      resistance to cyano- and nitro-substituted neonicotinoid insecticides.

PMID- 29183612
TI  - Suitable reference genes for accurate gene expression analysis in Papaver rhoeas
      under 2,4-D herbicide stress.
AB  - Resistance to 2,4-D (2,4-diclorophenoxyacetic acid) herbicide is increasing in
      various dicotyledonous weed species, including Papaver rhoeas, a weed infesting
      Southern European wheat crops. Non-target-site resistance to this herbicide is
      governed by a range of genes involved in herbicide stress response. To enable
      reliable measurement of gene expression levels in herbicide-resistant and
      susceptible plants it is necessary to normalize qPCR data using internal control
      genes with stable expression. In an attempt to find the best reference genes, the
      stability of seven candidate reference genes was assessed in plants resistant and
      susceptible to 2,4-D, subjected or not to herbicide stress. Using three
      statistical algorithms (geNorm, BestKeeper and NormFinder), the overall results
      revealed that glyceraldehyde-3-phosphate dehydrogenase, actin and ubiquitin were
      the most stable reference genes. The normalization expression levels of GH3
      (indole-3-acetic acid amido synthetase) and GST3 (glutathione S-transferase)
      which are two genes up-regulated following 2,4-D treatment, were determined to
      verify the stability of these selected reference genes. A sudden increase in GH3
      and GST3 expression was already detected 5h after herbicide application,
      confirming their involvement in plant response to 2,4-D. The validation results
      confirmed the applicability and accuracy of these reference genes. This study
      identified and validated reference genes in the non-model weed species P. rhoeas
      and these will facilitate gene expression analysis studies aimed at identifying
      functional genes associated with non-target-site resistance.

PMID- 29183613
TI  - High frequency of CYP337B3 gene associated with control failures of Helicoverpa
      armigera with pyrethroid insecticides in Brazil.
AB  - Control failures with the use of pyrethroid insecticides have been reported
      frequently for populations of Helicoverpa armigera (Hubner) in Brazil, since its
      detection in 2013. Here, we confirmed and investigated the metabolic mechanisms
      of pyrethroid resistance in H. armigera populations from Brazil. Mortality of H.
      armigera populations was lower than 50% at the highest dose (10MUg a.i./3rd
      instar larva) of the pyrethroids deltamethrin and fenvalerate in dose-response
      bioassays. Very low mortality (10 to 40%) was obtained at a diagnostic dose of
      10MUg a.i./larva for each pyrethroid in H. armigera populations collected from
      different agricultural regions in Brazil, from 2013 to 2016. In synergist
      bioassays, when larvae were treated with PBO synergist, the mortality of all
      populations tested was 100%. The frequency of the cytochrome P450 CYP337B3 gene
      was above 0.95 in all populations of H. armigera. We found only fourteen
      heterozygous H. armigera out of 497 individuals tested for this gene subfamily.
      Our results indicated that H. armigera populations from Brazil have different
      degrees of susceptibility to deltamethrin and fenvalerate, but all populations
      can be considered tolerant to pyrethroid insecticides. The chimeric P450 CYP337B3
      enzyme is one of the main mechanisms of pyrethroid resistance in Brazilian H.
      armigera populations.

PMID- 29183614
TI  - Synthesis, fungicidal activity and phloem mobility of phenazine-1-carboxylic acid
      alanine conjugates.
AB  - Phenazine-1-carboxylic acid (PCA) is a natural product that has been proven
      effective against a number of soil-borne fungal phytopathogens and registered for
      biofungicide against rice sheath blight in China. In order to improve the phloem
      mobility of phenazine-1-carboxylic acid (PCA), four PCA derivatives were designed
      and synthesized by conjugating PCA with l-alanine methyl ester, d-alanine methyl
      ester, l-alanine and d-alanine respectively. In vitro and planta bioassays
      results showed that conjugates L-PAM and D-PAM exhibited higher fungicidal
      activities against Rhizoctonia solani Kuhn than PCA while L-PA and D-PA were less
      active than PCA. The concentration of conjugates in Ricinus communis phloem sap
      was determined by HPLC. The results showed that only L-PA exhibited phloem
      mobility among these conjugates, and its concentration in Ricinus communis phloem
      sap increased with the increase of time (the maximum concentration was 12.69MUM
      within 5h). However, the results of pot experiments showed that L-PA and other
      conjugates didn't exhibited the inhibition for the growth of Rhizoctonia solani
      Kuhn in the lower leaves after treatment in the upper leaves of rice seedlings.
      This may be due to the poor plant absorbility for them or their too little amount
      of accumulation in the lower leaves.

PMID- 29183615
TI  - RNA interference of acetylcholinesterase in the Asian citrus psyllid, Diaphorina
      citri, increases its susceptibility to carbamate and organophosphate
      insecticides.
AB  - The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Lividae)
      transmits the Candidatus Liberibacter asiaticus, which causes citrus greening
      disease or Huanglongbing, (HLB). To date, there is no efficient cure for HLB
      disease and the control of D. citri using insecticides became the most important
      tools for the management of HLB. However, the extensive use of insecticides could
      increase D. citri resistance to these insecticides. The objective of this study
      was to investigate the effect of RNA interference of acetylcholinesterase (AChE)
      on the mortality and susceptibility of D. citri to the four major insecticides
      used in Florida. In this study, we used a consensus sequence derived from the two
      AChE genes and cholinesterase 2-like (ChE-2-like) gene to target all of the three
      genes. Treatment with dsRNA-AChE increased the mortality percentages of both
      nymphs and adults of D. citri. The mortality percentage increased with the
      increase in the concentration of applied dsRNA-AChE, and the highest mortality (>
      60%) was observed at the highest applied concentration (125ng/MUl). Treatments of
      nymphs or adults with dsRNA-AChE down-regulated the expression of the three
      targeted genes of D. citri. Silencing of AChE and ChE in D. citri nymphs
      increased the susceptibility of emerged adults to chlorpyrifos and carbaryl,
      which act as AChE inhibitors. However, treatment with dsRNA-AChE did not increase
      the susceptibility of emerged adults to imidacloprid, which acts as an agonist of
      nicotinic acetylcholine receptors. In the same manner, treatment of adults with
      dsRNA-AChE increased their susceptibility to chlorpyrifos and carbaryl, but did
      not affect their susceptibility to imidacloprid. The ANOVA did not show any
      significant increase in susceptibility of D. citri adults to fenpropathrin after
      treatment with dsRNA-AChE, either as nymphs or as adults. However, simple linear
      regression showed that treatment with dsRNA-AChE increased D. citri
      susceptibility to fenpropathrin, which indicated that AChE could be involved in
      the metabolism of fenpropathrin. Our results indicated that silencing of AChE and
      ChE genes in D. citri to increase its susceptibility to insecticides could be a
      promising tool for the control of this important vector.

PMID- 29183616
TI  - Characterization of a nicotinic acetylcholine receptor binding site for
      sulfoxaflor, a new sulfoximine insecticide for the control of sap-feeding insect
      pests.
AB  - Sulfoxaflor (SFX, IsoclastTM Active) is a recently developed sulfoximine
      insecticide that is highly effective against sap-feeding insect pests. SFX has
      been shown to act through an interaction with insect nicotinic acetylcholine
      receptors (nAChRs). SFX was previously found to interact weakly with the binding
      site for the neonicotinoid imidacloprid. However, radioligand displacement
      studies characterizing the binding site of the insecticide SFX itself have not
      been conducted. In this study, we report the characterization of a high affinity
      [3H]SFX Myzus persicae (green peach aphid, GPA) binding site with relatively low
      abundance. Through the evaluation of a set of SFX analogs, we have demonstrated
      that displacement of [3H]SFX shows an excellent correlation with GPA toxicity,
      and thus is toxicologically relevant. Comparison with the previously described
      methyl-SFX binding site information reveals differences with the SFX binding site
      that are discussed herein. [3H]SFX therefore represents a new tool for the
      characterization of insect nAChRs.

PMID- 29183617
TI  - Azadirachtin impact on mate choice, female sexual receptivity and male activity
      in Drosophila melanogaster (Diptera: Drosophilidae).
AB  - Azadirachtin, a neem compound (Azadirachta indica) with medical and anti-insect
      properties, is one the most successful botanical pesticides in agricultural use.
      However, its controversial impact on non-targeted species and its mechanism of
      action need to be clarified. In addition, Azadirachtin impact on pre- and post
      mating traits remains largely undocumented. The current study examined the
      effects of Azadirachtin on Drosophila melanogaster as a non-target and model
      species. Azadirachtin was applied topically at its LD50 (0.63MUg) on the day of
      adult emergence and its effect was evaluated on several traits of reproductive
      behavior: mate choice, male activity, female sexual receptivity, sperm storage
      and female sterility. In choice and no choice conditions, only male treatment
      reduced mating probability. Female treatment impaired mating probability only
      when males had the choice. Males' mating ability may have been impaired by an
      effect of the treatment on their mobility. Such an effect was observed in the
      actimeter, which revealed that treated males were less active than untreated
      ones, and this effect persisted over 8days. Azadirachtin treatment had, however,
      no effect on the nycthemeral rhythm of those males. Even when mating occurred,
      Azadirachtin treatment impaired post-mating responses especially when females or
      both sexes were treated: remating probability increases and female fertility
      (presence of larvae) decreases. No impairment was observed on the efficiency of
      mating, evaluated by the presence of sperm in the spermatheca or the ventral
      receptacle. Male treatment only had no significant effect on these post-mating
      responses. These findings provide clear evidence that Azadirachtin alters the
      reproductive behavior of both sexes in D. melanogaster via mating and post-mating
      processes.

PMID- 29183618
TI  - Encephalitis associated with antibodies against the NMDA receptor.
AB  - The encephalitis associated with antibodies against the N-methyl-D-aspartate
      receptor (NMDAR) is characterized by the presence of antibodies against the GluN1
      subunit of this receptor, resulting in symptoms that are similar to those
      observed in models of genetic or pharmacologic reduction of NMDARs. Patients are
      usually young adults, predominantly women, and children who develop, in a
      sequential manner, rapidly progressive symptoms including psychosis, abnormal
      movements, autonomic dysfunction, and coma. Epileptic seizures are variable and
      can occur throughout the course of the disease. The disease is often mistaken as
      viral encephalitis, primary psychiatric disorders, drug abuse, or neuroleptic
      malignant syndrome. About 50% of young women have an ovarian teratoma; in young
      girls and men the presence of a tumour is infrequent. In some patients, the
      disease is triggered by herpes simplex encephalitis. The recognition of anti
      NMDAR encephalitis is important because, despite its severity, most patients
      respond to immunotherapy.

PMID- 29183619
TI  - Non-sustained microvolt level T-wave alternans in congenital long QT syndrome
      types 1 and 2.
AB  - BACKGROUND: Patients with long QT syndrome (LQTS) are predisposed to polymorphic
      ventricular tachycardia (VT) during adrenergic stimulation. Microvolt T-wave
      alternans (MTWA) is linked to vulnerability to VT in structural heart disease.
      The prevalence of non-sustained MTWA (NS-MTWA) in LQTS is unknown. METHODS: 31
      LQT1, 42 LQT2, and 80 controls underwent MTWA testing during exercise. MTWA tests
      were classified per standardized criteria, and re-analyzed according to the
      modified criteria to account for NS-MTWA. RESULTS: LQT1 and LQT2 patients had a
      significantly higher frequency of late NS-MTWA (26% and 12%) compared to controls
      (0%). There was no significant difference between the groups with respect to
      sustained and early NS-MTWA. Late NS-MTWA was significantly associated with QTc.
      CONCLUSION: LQT1 and LQT2 patients had a higher prevalence of late NS-MTWA during
      exercise than matched controls. NS-MTWA likely reflects transient adrenergically
      mediated dispersion of repolarization, and could be a marker of arrhythmic risk
      in LQTS.

PMID- 29183620
TI  - Empowerment in Dermatology.
AB  - The term empowerment refers to any process that facilitates behavioral changes
      and encourages responsibility and making informed choices. The concept has been
      applied mainly to help patients with chronic conditions achieve therapeutic
      goals. The aim of the approach in health care is to enhance self-caring and self
      efficacy. The term derives from the English verb to empower meaning "to give
      (someone) the authority or power to do something" or "to make an individual or a
      group stronger or more powerful". One of the responsibilities of health
      professionals is to improve patients' knowledge and their ability to choose
      between the different alternatives available to them so that they can act
      accordingly. In this article, we review the various definitions of the term
      empowerment, the tools used to measure patient empowerment, the implications of
      the concept for the management of chronic disease, and its use in dermatological
      conditions.

PMID- 29183621
TI  - Capillary Malformations Treated With Sequential Pulsed Dye and Nd:YAG Laser
      Therapy: A Retrospective Study.
AB  - INTRODUCTION AND OBJECTIVE: Capillary malformations are the most common vascular
      malformations in childhood. The current treatment of choice is pulsed dye laser
      (PDL) therapy, but this frequently does not result in complete resolution. The
      search for alternative treatment strategies thus continues. In this study we
      describe our experience with the use of sequential dual-wavelength PDL and Nd:YAG
      laser therapy in patients with capillary malformations. MATERIAL AND METHODS: We
      conducted a retrospective, descriptive study of patients with capillary
      malformations treated with dual-wavelength PDL and Nd:YAG laser therapy between
      2006 and 2011. Four dermatologists rated the effectiveness of treatment on a
      scale of 10 to 0. We also investigated the potential value of the following
      factors as predictors of better treatment response: sex, malformation size and
      color, and presence of associated hypertrophy. Adverse effects were also
      analyzed. RESULTS: We studied 71 patients and most of them experienced a
      statistically significant improvement after treatment. More favorable responses
      were observed for violaceous malformations, lesions with associated hypertrophy,
      and smaller lesions. Adverse effects were reported for 26.76% of patients, and
      the most common effect was the appearance of isolated areas of skin atrophy.
      CONCLUSIONS: We consider that sequential dual-wavelength PDL and ND:YAG laser
      therapy is an effective alternative for treating capillary malformations in
      selected patients.

PMID- 29183622
TI  - Ultrasound Diagnosis of Nodular Hidradenoma.

PMID- 29183624
TI  - Corrigendum to "APOE epsilon4 allele modifies the association of lead exposure
      with age-related cognitive decline in older individuals" [Environ. Res. 151
      (2016) 101-105].

PMID- 29183623
TI  - Role of angiopoietin-like 3 (ANGPTL3) in regulating plasma level of low-density
      lipoprotein cholesterol.
AB  - BACKGROUND AND AIMS: Angiopoietin-like 3 (ANGPTL3) has emerged as a key regulator
      of lipoprotein metabolism in humans. Homozygous loss of ANGPTL3 function causes
      familial combined hypolipidemia characterized by low plasma levels of
      triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density
      lipoprotein cholesterol (LDL-C). While known effects of ANGPTL3 in inhibiting
      lipoprotein lipase and endothelial lipase contribute to the low TG and HDL-C,
      respectively, the basis of low LDL-C remains unclear. Our aim was to explore the
      role of ANGPTL3 in modulating plasma LDL-C. METHODS: We performed RNAi-mediated
      gene silencing of ANGPTL3 in five mouse models and in human hepatoma cells. We
      validated results by deleting ANGPTL3 gene using the CRISPR/Cas9 genome editing
      system. RESULTS: RNAi-mediated Angptl3 silencing in mouse livers resulted in very
      low TG, HDL-C and LDL-C, a pattern similar to the human phenotype. The effect was
      observed in wild-type and obese mice, while in hCETP/apolipoprotein (Apo) B-100
      double transgenic mice, the silencing decreased LDL-C and TG, but not HDL-C. In a
      humanized mouse model (Apobec1-/- carrying human ApoB-100 transgene) deficient in
      the LDL receptor (LDLR), Angptl3 silencing had minimum effect on LDL-C,
      suggesting the effect being linked to LDLR. This observation is supported by an
      additive effect on LDL-C between ANGPTL3 and PCSK9 siRNAs. ANGPTL3 gene deletion
      induced cellular long-chain TG and ApoB-100 accumulation with elevated LDLR and
      LDLR-related protein (LRP) 1 expression. Consistent with this, ANGPTL3 deficiency
      by gene deletion or silencing reduced nascent ApoB-100 secretion and increased
      LDL/VLDL uptake. CONCLUSIONS: Reduced secretion and increased uptake of ApoB
      containing lipoproteins may contribute to the low LDL-C observed in mice and
      humans with genetic ANGPTL3 deficiency.

PMID- 29183625
TI  - Aluminum's preferential binding site in proteins: sidechain of amino acids versus
      backbone interactions.

PMID- 29183626
TI  - Does nutritional intervention maintain its prognostic benefit in the long term
      for malnourished patients hospitalised for heart failure?
AB  - OBJECTIVE: To assess the long-term effect of nutritional intervention on
      malnourished, hospitalised patients with heart failure (HF). METHODS: A total of
      120 malnourished patients hospitalized for HF were randomised to undergo (or not)
      an individual nutritional intervention for 6 months. The primary event was the
      combination of all-cause death and readmission for HF. We performed an intent-to
      treat analysis and assessed the effect of the intervention at 24 months. RESULTS:
      The combined event occurred in 47.5% of the intervention group and in 73.8% of
      the control group (hazard ratio: 0.45; 95% confidence interval: 0.28-0.72;
      P=.001). Thirty-nine percent of the intervention group and 59% of the control
      group died (hazard ratio: 0.53; 95% confidence interval: 0.31-0.89; P=.017).
      CONCLUSION: A nutritional intervention for malnourished patients hospitalised for
      HF maintains its prognostic benefit in the long-term follow-up.

PMID- 29183627
TI  - Neoplastic growth-restricting effects of fluvastatin in systemic malignancies.

PMID- 29183628
TI  - The Pharmacokinetics of Fumaric Acid Esters Reveal Their In Vivo Effects.
AB  - Fumaric acid ester-based drugs are used for the treatment of psoriasis and
      multiple sclerosis. All licensed fumaric acid ester drugs contain
      dimethylfumarate (DMF) as the main active component. Due to the expanding use of
      oral DMF there is growing scientific interest in determining its as-yet-unknown
      mechanism of action. However, the pharmacology and chemistry of DMF are often not
      fully considered in the design and interpretation of experiments; namely, that
      while DMF is plasma-membrane permeable and has strong effects on many cell types
      in vitro, it is rapidly metabolized into membrane-impermeable monomethylfumarate
      (MMF) in vivo. This can lead to significant biological effects being erroneously
      assigned to DMF. Understanding the pharmacology of DMF means that future work can
      more closely reflect the state in vivo.

PMID- 29183629
TI  - Is human papillomavirus genotype important in predicting disease progression in
      women with biopsy-proven negative or CIN1 of atypical squamous cell of
      undetermined significance (ASC-US) cytology?
AB  - OBJECTIVES: Our aim was to estimate the risk of disease incidence in women with
      atypical squamous cell of undetermined significance (ASC-US) without histology
      proven cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by human
      papillomavirus (HPV) genotype. METHODS: Between January 2002 and September 2010,
      incidence of CIN2+ in 2880 women including 2172 with ASC-US and histology-proven
      negative and 708 with ASC-US with histology-proven CIN1 was investigated.
      Baseline HR-HPV status was determined by the hybrid capture II assay (HC2) and HR
      HPV genotype by the HPV DNA chip test (HDC). Cumulative incidence and hazard
      ratios were estimated to explore differences between index data and associations
      with CIN2+. RESULTS: Of the 2880 women, the HC2 was positive in 1509 women
      (52.4%) and the HDC was positive in 1563 women (54.3%). The overall agreement
      between the HDC and HC2 was 97.4%. One hundred ninety (6.6%) patients developed
      CIN2+. The 5-year cumulative incidence rate of CIN2+ in HPV-16, HPV-31, HPV-52,
      and HPV-58 were 16.7%, 15.1%, 12.6%, and 12.9%, respectively. On multivariate
      analysis, being positive in HPV-16 (hazards ratio [HR]=2.431; 95% CI, 1.789
      3.332; P<0.01), HPV-31 (HR=2.335; 95% CI, 1.373-3.971; P<0.01), HPV-52 (HR=1.592;
      95% CI, 1.031-2.458; P=0.03), and HPV-58 (HR=1.650; 95% CI, 1.132-2.407; P<0.01)
      were significantly associated with developing CIN2+ compared to being negative
      for that type. CONCLUSIONS: Among women with ASC-US, HPV-16, HPV-31, HPV-52, or
      HPV-58 positive women may need intensified follow-up as they have the highest
      risk of becoming CIN2+.

PMID- 29183631
TI  - Birth weight to placenta weight ratio and its relationship to ultrasonic
      measurements, maternal and neonatal morbidity: A prospective cohort study of
      nulliparous women.
AB  - INTRODUCTION: Birth weight to placenta weight (BWPW)-ratio is an indicator of the
      ability of the placenta to maintain adequate nutrient supply to the fetus. We
      sought to investigate the relationship between BWPW-ratio with fetal growth,
      utero-placental Doppler and neonatal and maternal morbidity. METHODS: We studied
      a group of 3311 women recruited to a prospective cohort study of nulliparous
      women (Rosie Hospital, Cambridge, UK) who delivered a live born infant at term
      and whose placental weight and birth weight were known. Ultrasonic indices and
      BWPW ratio were converted to gestational age adjusted z scores. Analysis of
      continuous variables was by multivariable linear regression. BWPW ratio was also
      categorized (lowest or highest quintile, both referent to quintiles 2 to 4) and
      associations with adverse outcomes analyzed using multivariable logistic
      regression. RESULTS: Lowest quintile of BWPW-ratio was associated (adjusted odds
      ratio [95% CI], P) with both neonatal morbidity (1.55 [1.12-2.14], 0.007) and
      maternal diabetes (1.75 [1.18-2.59], 0.005). Highest quintile of BWPW ratio was
      associated with a reduced risk of maternal obesity (0.71 [0.53 to 0.95], 0.02)
      and preeclampsia (0.51 [0.31 to 0.84], 0.008), but higher (adjusted z score [95%
      CI], P) uterine artery Doppler mean pulsatility index (PI) at 20 weeks of
      gestation (0.09 [0.01-0.18], 0.04) and umbilical artery Doppler PI at 36 weeks of
      gestation (0.16 [0.07-0.25], <0.001). CONCLUSION: BWPW-ratio is related to
      ultrasonic measurements and both neonatal and maternal morbidity. Therefore, this
      ratio may be an indicative marker of immediate and longer term health risks for
      an individual.

PMID- 29183630
TI  - Where, When, and How: Are they all sensorimotor? Towards a unified view of the
      dorsal pathway in vision and audition.
AB  - Dual processing streams in sensory systems have been postulated for a long time.
      Much experimental evidence has been accumulated from behavioral,
      neuropsychological, electrophysiological, neuroanatomical and neuroimaging work
      supporting the existence of largely segregated cortical pathways in both vision
      and audition. More recently, debate has returned to the question of overlap
      between these pathways and whether there aren't really more than two processing
      streams. The present piece defends the dual-system view. Focusing on the
      functions of the dorsal stream in the auditory and language system I try to
      reconcile the various models of Where, How and When into one coherent concept of
      sensorimotor integration. This framework incorporates principles of internal
      models in feedback control systems and is applicable to the visual system as
      well.

PMID- 29183632
TI  - Recommendations for perioperative management of new pharmacological antifibrotic
      therapy in idiopathic pulmonary fibrosis.

PMID- 29183633
TI  - Guidelines, algorithms, and recommendations during the management of the
      difficult airways in the thoracic surgical patient: Are they supported by
      evidence based?

PMID- 29183634
TI  - Group 6. Modalities and frequency of monitoring of patients with adrenal
      insufficiency. Patient education.
AB  - Patients with adrenal insufficiency require regular, specialised monitoring in
      order to optimise their replacement therapy, to detect signs of under- and over
      dosage, and to examine for possible associated disorders (auto-immune disorders
      in the case of auto-immune primary adrenal insufficiency either isolated or as
      part of auto-immune polyendocrinopathy syndrome type 1; illnesses with underlying
      monogenic causes). The transition period between adolescence and adulthood
      represents an added risk of a breakdown in monitoring which requires particular
      attention from medical teams and coordination between adult and pediatric medical
      teams. It is essential to encourage patient autonomy in the management of their
      illness, notably their participation in treatment education programs, in
      particular programs that target avoidance of, or early treatment of acute adrenal
      insufficiency. The principal educational objectives for patients in such programs
      are: to be in possession of, and carry the necessary tools for their treatment in
      an emergency; to be able to identify situations of increased risk and the early
      signs of adrenal crisis; to know how to adjust their oral glucocorticoid
      treatment; to be capable of administering hydrocortisone by subcutaneous
      injection; to be able to predict and therefore adjust treatment to different
      situations (heat, physical exercise, travel) and to be able to correctly use the
      appropriate resources of the healthcare services. Other programs could also be
      developed to respond to needs and expectations of patients, notably concerning
      the adjustment of hydrocortisone dosage to avoid overdose in the context of
      chronic fatigue syndrome.

PMID- 29183635
TI  - Hypothermia indices among severely injured trauma patients undergoing urgent
      surgery: A single-centred retrospective quality review and analysis.
AB  - BACKGROUND: Hypothermia (<36 degrees C) exacerbates trauma-induced coagulopathy
      and worsens morbidity and mortality among severely injured trauma patients; there
      is a paucity of published data describing how well trauma centres adhere to
      standards regarding measurement of temperature, and best practices for preventing
      and treating hypothermia. METHODS: We completed a retrospective quality audit of
      all severely injured trauma patients (Injury Severity Score (ISS>=20)) who had
      urgent surgery at Sunnybrook Health Sciences Centre (SHSC) between 2010 and 2014.
      Information regarding temperature monitoring was evaluated over the course of the
      initial resuscitation and admission. Independent risk factors for in-hospital
      mortality were elucidated through a multivariable regression analysis. RESULTS:
      Out of a total of 4492 trauma patients, 495 were severely-injured and went to the
      operating room (OPR) after being treated in the trauma bay (TB) at SHSC between
      2010 and 2014. The majority of the patients were male (n=384, 77.6%) and had a
      blunt mechanism of injury (n=391, 79.0%). The median ISS score was 29
      (interquartile range (IQR) 26, 35). Eighty-nine (17.9%) patients died; 26 (5.2%)
      of these patients died intra-operatively. Less than one fifth of patients
      (n=82,16.6%) received a temperature measurement during pre-hospital transport
      phase. Upon arrival to the TB, almost two-thirds (n=301, 60.8%) of patients had
      their temperature recorded and a similar proportion (n=175, 58.1%) of those
      patients were hypothermic (<36 degrees C). In the OPR, close to 80% (n=389,
      78.6%) of patients had their temperature measured on both arrival; almost 60%
      (n=223, 57.3%) were hypothermic on arrival. Almost all patients had their
      temperature measured upon arrival to the ICU or specialized ward (n=450, 98.3%).
      Warming initiatives were documented in only 36 (7.3%) patients in the TB, yet
      documented in almost all patients in OR (n=464, 93.7%). An increased risk of in
      hospital mortality was correlated with not taking a temperature measurement in
      the TB (Odds Ratio (OR) 2.86 (95% Confidence Interval (CI) [1.64-4.99]) or OPR
      (OR 4.66 (95% CI [2.50-8.69]). CONCLUSIONS: A majority of severely injured trauma
      patients are hypothermic well into the perioperative period after initial
      admission. An absence of having temperature measurement during initial
      hospitalization is associated with increased in-hospital mortality amongst this
      patient group. Quality improvement initiatives should aim to strive for ongoing
      temperature measurement as a key performance indicator and early prevention and
      treatment of hypothermia during initial resuscitation.

PMID- 29183636
TI  - Clinical Guidance to Tattooing and Piercing Among Youth.

PMID- 29183637
TI  - Cell-spray auto-grafting technology for deep partial-thickness burns: Problems
      and solutions during clinical implementation.
AB  - Cell-spray autografting is an innovative early treatment option for deep partial
      thickness burn wounds. As an alternative to non-operative management, cell-spray
      autografting can achieve rapid wound re-epithelialization, particularly in large
      wounds. When compared to traditional mesh autografting for deep partial-thickness
      burn wounds, cell-spray autografting can accomplish re-epithelialization with a
      much smaller donor site. In this review, we describe the development of a
      biomedical engineering method for isolation and immediate distribution of
      autologous, non-cultured, adult epidermis-, and adult dermis-derived stem cells.
      We present data on cell isolation procedures in 44 patients with deep partial
      thickness burns performed over five years under an innovative practice IRB.
      Treated patients presented with a variety of burn wound etiologies and a wide
      range of TBSA. Overall clinical results were very satisfying. The average
      hospital length of stay following treatment was seven days. Over the time period,
      the donor-site to burn-wound surface area ratio was enhanced from 1:80 to 1:100.
      A detailed analysis of all process-related biotechnology and operative problems,
      pitfalls, and solutions was performed and is reported herein. Strategies for
      future clinical studies are discussed.

PMID- 29183638
TI  - [Proposed development of a geriatric oncology unit. Times of change: Our
      reality].
AB  - Age is one of the main risk factors for the development of cancer. It is expected
      that the progressive aging of the population will have an unprecedented impact on
      the incidence of various tumours. In fact, the management of elderly cancer
      patients is already a major public health problem in developed countries.
      However, elderly patients have systematically been excluded from cancer drug
      studies or protocol development. This has left health professionals in uncharted
      territory, without proper tools to address the multiple difficulties that arise
      in the treatment of these patients. A comprehensive geriatric assessment may
      serve as an ideal tool for the correct detection of hidden problems, facilitating
      treatment decisions in these complex patients, and integrating the care of
      patients with comorbidities.

PMID- 29183639
TI  - Systematic review and meta-analysis of prognostic role of splenic vessels
      infiltration in resectable pancreatic cancer.
AB  - BACKGROUND: Identification of factors associated with dismal survival after
      surgery in resectable pancreatic ductal adenocarcinoma is important to select
      patients for neoadjuvant treatment. The present meta-analysis aimed to compare
      the results of distal pancreatectomy for resectable adenocarcinoma of the
      pancreatic body-tail with and without splenic vessels infiltration. METHODS: A
      systematic search was performed of PubMed, Embase and the Cochrane Library in
      accordance with PRISMA guidelines. The inclusion criteria were studies including
      patients who underwent distal pancreatectomy for pancreatic cancer with or
      without splenic vessels infiltration. 5-year overall survival (OS) was the
      primary outcomes. Meta-analysis was carried out applying time-to-event method.
      RESULTS: Six articles with 423 patients were analysed. Patients with pathological
      splenic artery invasion had a worse survival compared with those without
      infiltration (Hazard ratio 1.76, 95% CI 1.36-2.28; P < 0.0001). A similar results
      was found when considering pathological splenic vessels infiltration, showing
      that survival was significantly poorer when splenic vein infiltration was present
      (Hazard ratio 1.51, 95% CI 1.19-1.93; P = 0.0009). CONCLUSIONS: This meta
      analysis showed worse survival for patients with splenic vessels infiltration
      undergoing distal pancreatectomy for pancreatic cancer. Splenic vessels
      infiltration represents the stigmata of a more aggressive disease, although
      resectable.

PMID- 29183640
TI  - Influence of the primary tumour location in patients undergoing surgery for
      colorectal liver metastases.
AB  - BACKGROUND: The prognosis of patients undergoing liver resection for colorectal
      liver metastases (CLM) seems to be altered when the primary tumour is right
      sided. However, data are lacking and conflicting. We aimed to evaluate the
      influence of the primary tumour location on oncologic outcomes following such
      surgery. METHODS: We retrospectively analysed prospectively collected data from
      376 consecutive patients who underwent liver surgery for CLM between June 2010
      and August 2015. We compared the outcomes of patients with right colon tumours
      and those with left colorectal tumours. The splenic flexure was used as the cut
      off point to determine the anatomic primary site. RESULTS: Among the 364 patients
      eligible, 74 (20.3%) had a right-sided primary tumour. These patients were older,
      had a poorer American Society of Anaesthesiologists status and had fewer node
      positive primary tumours. The CLM characteristics were similar between both
      groups. Median PFS was not significantly different between the two groups at 9.9
      months, as well as the pattern of recurrence. Median OS was shorter for patients
      with right-sided primary tumour (34.6 versus 45.3 months, p = 0.035). Similar
      results were observed when patients with rectal tumour were excluded from
      analysis (34.6 vs. 47.5 months, p = 0.007). Primary tumour site was an
      independent prognosis factor in multivariate analysis. CONCLUSION: Right-sided
      location of the primary tumour is associated with worse OS after surgery for CLM,
      but seems to have no influence on PFS, and on the pattern of recurrence.

PMID- 29183641
TI  - Radiological visibility of an immediate contrast medium side-effect.

PMID- 29183642
TI  - Tick-borne diseases and autoimmunity: A comprehensive review.
AB  - Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by
      ticks, which portray wide heterogeneity and global distribution. TBDs may present
      acute clinical pictures that resemble those of autoimmune diseases (i.e.,
      musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal
      failure, etc.), and in some cases infection is considered a triggering factor for
      autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease,
      vasculitides). The clinician should consider TBDs among the differential
      diagnoses when approaching autoimmune-like signs in areas of tick infestation.
      Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic
      approach (i.e., clinical history, physical examination and laboratory tests) are
      necessary to confirm TBDs. Further, control and prevention of TBDs is warranted.
      Research in the fields of ticks microbiome and vaccination (i.e., wildlife and
      humans) are ahead to control vector transmission and bacterial infection. This
      review offers a comprehensive update on TBDs and their relationship with
      autoimmunity.

PMID- 29183643
TI  - Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific
      antagomirs in vivo.
AB  - In T lymphocytes, expression of miR-148a is induced by T-bet and Twist1, and is
      specific for pro-inflammatory Th1 cells. In these cells, miR-148a inhibits the
      expression of the pro-apoptotic protein Bim and promotes their survival. Here we
      use sequence-specific cholesterol-modified oligonucleotides against miR-148a
      (antagomir-148a) for the selective elimination of pro-inflammatory Th1 cells in
      vivo. In the murine model of transfer colitis, antagomir-148a treatment reduced
      the number of pro-inflammatory Th1 cells in the colon of colitic mice by 50% and
      inhibited miR-148a expression by 71% in the remaining Th1 cells. Expression of
      Bim protein in colonic Th1 cells was increased. Antagomir-148a-mediated reduction
      of Th1 cells resulted in a significant amelioration of colitis. The effect of
      antagomir-148a was selective for chronic inflammation. Antigen-specific memory Th
      cells that were generated by an acute immune reaction to nitrophenylacetyl
      coupled chicken gamma globulin (NP-CGG) were not affected by treatment with
      antagomir-148a, both during the effector and the memory phase. In addition,
      antibody titers to NP-CGG were not altered. Thus, antagomir-148a might qualify as
      an effective drug to selectively deplete pro-inflammatory Th1 cells of chronic
      inflammation without affecting the protective immunological memory.

PMID- 29183644
TI  - The meaning of personal diaries to children and families in the paediatric
      intensive care unit: A qualitative study.
AB  - OBJECTIVE: To explore children's' and families' experiences of using intensive
      care diaries after discharge and the role of diaries in the process of recovering
      from a stay in the paediatric intensive care unit. DESIGN AND SETTING:
      Qualitative, exploratory design. Data collection consisted of semi-structured
      interviews with five children and their families, conducted four to six months
      after discharge from the intensive care unit. Inclusion criteria were children
      and their families, with a stay for more than three days who had a diary written
      for them. Data were analysed using thematic analysis FINDINGS: Three main themes
      emerged: (i) value to the entire family, (ii) creating memories, (iii) the
      importance of pictures. CONCLUSION: Diaries were used after discharge as a
      support for both children and families and played a role in making the paediatric
      intensive care experience meaningful by providing explanations and coherence. The
      findings suggest that a diary can serve as a catalyst for the coping process of
      the family unit. Findings also confirm how the children's memories are
      characterised by a sense of unreality. The diary could thus help fill in some of
      the missing picture to support the children in understanding their story.

PMID- 29183645
TI  - Survivorship Analysis and Clinical Outcomes of Transtibial Pullout Repair for
      Medial Meniscus Posterior Root Tears: A 5- to 10-Year Follow-up Study.
AB  - PURPOSE: This study investigated the clinical outcomes and mid- to long-term
      survival rates in patients undergoing transtibial pullout repair of medial
      meniscus posterior root tears (MMPRTs) after a minimum follow-up of 5 years.
      METHODS: Between 2005 and 2011, patients with MMPRTs who had been followed for at
      least 5 years after undergoing transtibial pullout repair were recruited.
      Participants were identified using medical records and information in a
      prospectively collected database. Clinical outcomes were assessed based on a
      comparison of patient preoperative Lysholm scores and their scores at the final
      follow-up. A Kaplan-Meier survival analysis was used to investigate the survival
      rates of repair procedures. Clinical failures were defined as cases requiring
      conversion to total knee arthroplasty (TKA) or having final Lysholm score <65 or
      less than their preoperative scores. RESULTS: Overall, 91 patients (mean age,
      58.7 +/- 9.7 years) were included: the mean follow-up duration was 84.8 +/- 13.8
      months. Among these patients, the mean Lysholm score improved significantly from
      51.8 +/- 7.9 preoperatively to 83.0 +/- 11.1 at the final follow-up (P < .001).
      Overall, 4 patients failed due to conversion to TKA (n = 1) or having final
      Lysholm scores <65 or less than the preoperative scores (n = 3). The overall
      Kaplan-Meier probabilities of survival after repair were 99% at 5 years, 98% at 6
      years, 95% at 7 years, and 92% at 8 years. CONCLUSIONS: Among patients with
      MMPRTs, transtibial pullout repair demonstrated a high clinical survival rate and
      the patients demonstrated clinical improvement, based on mid- and long-term
      follow-up examinations. LEVEL OF EVIDENCE: Level IV, retrospective uncontrolled
      case series.

PMID- 29183646
TI  - A risk score to predict the absence of left ventricular reverse remodeling:
      Implications for the timing of ICD implantation in primary prevention.
AB  - BACKGROUND: A prophylactic implantable cardioverter defibrillator (ICD) in
      patients with heart failure and reduced left ventricular ejection fraction
      (HFrEF) is only indicated when left ventricular ejection fraction (LVEF)
      reassessment remains <=35% after 3-6 months on optimal pharmacological therapy.
      However, LVEF may not improve during this period and the patient may be exposed
      to an unnecessary risk of sudden cardiac death. This study aimed to determine the
      incidence and predictors of the absence of left ventricular reverse remodeling
      (LVRR) after pharmacological treatment optimization in patients with HFrEF to
      design a risk score of absence of LVRR. METHODS: Consecutive outpatients with
      LVEF <=35% were included in this observational prospective study. Up-titration of
      angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers
      (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and
      ivabradine was performed in our Heart Failure (HF) Unit. The absence of LVRR was
      defined as the persistence of an LVEF <=35% at the 6-month follow-up. RESULTS:
      One hundred and twenty patients were included. At the 6-month follow-up, 64%,
      76%, 72%, and 7% of patients were at 100% of the target dose of ACE
      inhibitors/ARBs, beta-blockers, MRAs, and ivabradine, respectively. LVRR was
      observed in 48% of the patients. Ischemic cardiomyopathy, prolonged HF duration,
      and larger left ventricular end-diastolic diameter index (LVEDDI) were
      independent predictors of the absence of LVRR. The risk score based on these
      predictors showed a c-statistic value of 0.81. CONCLUSIONS: Pharmacological
      treatment optimization is associated with LVRR in approximately half of cases,
      reducing potential ICD indications in parallel. However, ischemic cardiomyopathy,
      prolonged HF duration, and larger LVEDDI predict the absence of LVRR and favor
      ICD implantation without delay. The risk score based on the former predictors may
      help the clinician with the timing of ICD implantation.

PMID- 29183647
TI  - In-vitro digestion of curcumin loaded chitosan-coated liposomes.
AB  - Liposomes are considered a major route for encapsulation of hydrophilic and
      hydrophobic molecules. Chitosan coated liposomes could represent an alternative
      way as a carrier for delivery of drugs in human body. In this study the
      preparation and applicability of chitosan-coated liposomes containing curcumin as
      well as curcumin loaded anionic liposomes were evaluated. The applicability of
      the carriers was tested by means of an in-vitro digestion procedure allowing for
      measurement of the bioaccessibility of ingested curcumin. Values of diameter,
      polydispersity index and surface charge for curcumin loaded anionic liposomes
      obtained through dynamic light scattering and zeta-potential measurements were
      129nm, 0.095 and -49mV, respectively. After chitosan-coating, diameter and
      polydispersity index remain unvaried while the surface charge gets positive.
      Slightly higher curcumin concentrations were found after the mouth and the
      stomach digestion phases when curcumin was loaded in anionic liposomes. On the
      contrary, after the intestinal phase, a higher percentage of curcumin was found
      when chitosan-coated liposomes were used as carrier, both in the raw digesta and
      in the bile salt micellar phase. It was shown that the presence of a positively
      charged surface allows a better absorption of curcumin in the small intestine
      phase, which increases the overall curcumin bioavailability. The mechanism behind
      these results can be understood from the composition of the different
      environments generated by the digestive fluids that differently interact with
      anionic or cationic surfaces.

PMID- 29183648
TI  - Re: re: Mandibular stability using sliding compared with conventional four-hole
      plates for fixation after bilateral sagittal split ramus osteotomy for mandibular
      setback.

PMID- 29183649
TI  - A happiness degree predictor using the conceptual data structure for deep
      learning architectures.
AB  - BACKGROUND AND OBJECTIVE: Happiness is a universal fundamental human goal. Since
      the emergence of Positive Psychology, a major focus in psychological research has
      been to study the role of certain factors in the prediction of happiness. The
      conventional methodologies are based on linear relationships, such as the
      commonly used Multivariate Linear Regression (MLR), which may suffer from the
      lack of representative capacity to the varied psychological features. Using Deep
      Neural Networks (DNN), we define a Happiness Degree Predictor (H-DP) based on the
      answers to five psychometric standardized questionnaires. METHODS: A Data
      Structure driven architecture for DNNs (D-SDNN) is proposed for defining a HDP in
      which the network architecture enables the conceptual interpretation of
      psychological factors associated to happiness. Four different neural network
      configurations have been tested, varying the number of neurons and the presence
      or absence of bias in the hidden layers. Two metrics for evaluating the influence
      of conceptual dimensions have been defined and computed: one quantifies the
      influence weight of the conceptual dimension in absolute terms and the other one
      pinpoints the direction (positive or negative) of the influence. MATERIALS: A
      cross-sectional survey targeting non-institutionalized adult population residing
      in Spain was completed by 823 cases. The total of 111 elements of the survey are
      grouped by socio-demographic data and by five psychometric scales (Brief COPE
      Inventory, EPQR-A, GHQ-28, MOS-SSS and SDHS) measuring several psychological
      factors acting one as the outcome (SDHS) and the four others as predictors.
      RESULTS: Our D-SDNN approach provided a better outcome (MSE: 1.46.10-2) than MLR
      (MSE: 2.30.10-2), hence improving by 37% the predictive accuracy, and allowing to
      simulate the conceptual structure. CONCLUSIONS: We observe a better performance
      of Deep Neural Networks (DNN) with respect to traditional methodologies. This
      demonstrates its capability to capture the conceptual structure for predicting
      happiness degree through psychological variables assessed by standardized
      questionnaires. It also permits to estimate the influence of each factor on the
      outcome without assuming a linear relationship.

PMID- 29183650
TI  - Insights to bioprocess and treatment competence of urban wetlands.
AB  - Wetlands play a major role in the recharge of groundwater resources, maintenance
      of water quality (remediation), moderate microclimate while supporting local
      livelihood through provision of fish, fodder, etc. The present study aims to
      investigate algal-bacterial consortium as a function of residence time with the
      water quality dynamics in two major wetlands in Bangalore city, India. Over
      thirty-two genera of algae were recorded with more than 40 species in the lakes
      and two dominant bacterial assemblages. The higher Ammonium-N content favoured
      the growth of these members. Significant correlation was observed between the
      nutrient concentrations and the community structure at the inflows and the
      outflows. The algal community showed negative correlation to filterable COD and
      high nutrients levels while bacterial abundance was observed under high loadings.
      The green algae Chlorophyceae (Chlorella blooms), which are indicators of
      nutrient enrichment were observed predominantly, that needs an immediate
      attention. Higher overall treatment efficiency was observed in terms of CNP
      removal during the Pre-monsoon season attributed to absence of macrophytes cover
      and rapid growth of algal assemblage's due to higher temperature regimes with
      adequate solar insolation.

PMID- 29183651
TI  - Corrigendum to "Image-guided ablation of renal cell carcinoma" [Clin Radiol 72
      (8) (2017) 636-644].

PMID- 29183652
TI  - Restless legs syndrome is highly prevalent in patients with postpolio syndrome.

PMID- 29183653
TI  - Chimeric mice with humanized liver: Application in drug metabolism and
      pharmacokinetics studies for drug discovery.
AB  - Predicting human drug metabolism and pharmacokinetics (PK) is key to drug
      discovery. In particular, it is important to predict human PK, metabolite
      profiles and drug-drug interactions (DDIs). Various methods have been used for
      such predictions, including in vitro metabolic studies using human biological
      samples, such as hepatic microsomes and hepatocytes, and in vivo studies using
      experimental animals. However, prediction studies using these methods are often
      inconclusive due to discrepancies between in vitro and in vivo results, and
      interspecies differences in drug metabolism. Further, the prediction methods have
      changed from qualitative to quantitative to solve these issues. Chimeric mice
      with humanized liver have been developed, in which mouse liver cells are mostly
      replaced with human hepatocytes. Since human drug metabolizing enzymes are
      expressed in the liver of these mice, they are regarded as suitable models for
      mimicking the drug metabolism and PK observed in humans; therefore, these mice
      are useful for predicting human drug metabolism and PK. In this review, we
      discuss the current state, issues, and future directions of predicting human drug
      metabolism and PK using chimeric mice with humanized liver in drug discovery.

PMID- 29183654
TI  - [Safety of SGLT2 inhibitors. A review of the adverse drug reactions registered in
      a national database].
AB  - OBJECTIVE: To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose
      Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the
      market. MATERIAL AND METHODS: An analysis was made of all the notifications
      registered in the Spanish Pharmacovigilance System of drugs for human use,
      arising from the use of SGLT2i. RESULTS: A total of 311 notifications were
      recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26.05%) to
      empagliflozin, and 61 (19.61%) to canagliflozin. There was a ratio of 52.1% women
      to 47.9% men. The mean age was 62.07+/-12.17years. There were 167 (53.7%)
      notifications were classified as non-serious and 144 (46.3%) as serious. A total
      of 534 ADRs were notified, with the most common being urinary tract infections in
      37 (6.9%) cases, diabetic ketoacidosis in 30 (5.6%), balanoposthitis in 24
      (4.5%), ketoacidosis in 16 (3%), vulvovaginal candidiasis in 16 (3%), dizzy
      spells in 11 (2.1%), and 10 (1.9%) with dysuria, Candida balanitis, and
      vulvovaginal pruritus. As regards the outcomes of the 534 ADRs, 55.6% recovered
      with no sequelae, with 14% still recovering, 4.9% not recovered, fatal in 1.1%,
      and unknown in 24.3%. CONCLUSIONS: The majority of the ADRs notified are
      infections of the urogenital tract, ketoacidosis, and kidney damage. Although the
      majority of the former were not serious, the ketoacidosis and kidney damage were,
      leading to hospital admission and being life threatening in some patients. For
      these reasons, it is recommended that they are, prescribed with caution, the
      warnings published by the health authorities consulted, as well as notify any ADR
      that is suspected in this therapeutic group, in order to improve and provide us
      with further knowledge.

PMID- 29183656
TI  - Plasma metabolomics reveal the correlation of metabolic pathways and Prakritis of
      humans.
AB  - BACKGROUND: Ayurveda, an ancient Indian medicinal system, has categorized human
      body constitutions in three broad constitutional types (prakritis) i.e. Vata,
      Pitta and Kapha. OBJECTIVES: Analysis of plasma metabolites and related pathways
      to classify Prakriti specific dominant marker metabolites and metabolic pathways.
      MATERIALS AND METHODS: 38 healthy male individuals were assessed for dominant
      Prakritis and their fasting blood samples were collected. The processed plasma
      samples were subjected to rapid resolution liquid chromatography-electrospray
      ionization-quadrupole time of flight mass spectrometry (RRLC-ESI-QTOFMS). Mass
      profiles were aligned and subjected to multivariate analysis. RESULTS: Partial
      least square discriminant analysis (PLS-DA) model showed 97.87% recognition
      capability. List of PLS-DA metabolites was subjected to permutative Benjamini
      Hochberg false discovery rate (FDR) correction and final list of 76 metabolites
      with p < 0.05 and fold-change > 2.0 was identified. Pathway analysis using
      metascape and JEPETTO plugins in Cytoscape revealed that steroidal hormone
      biosynthesis, amino acid, and arachidonic acid metabolism are major pathways
      varying with different constitution. Biological Go processes analysis showed that
      aromatic amino acids, sphingolipids, and pyrimidine nucleotides metabolic
      processes were dominant in kapha type of body constitution. Fat soluble vitamins,
      cellular amino acid, and androgen biosynthesis process along with branched chain
      amino acid and glycerolipid catabolic processes were dominant in pitta type
      individuals. Vata Prakriti was found to have dominant catecholamine, arachidonic
      acid and hydrogen peroxide metabolomics processes. CONCLUSION: The
      neurotransmission and oxidative stress in vata, BCAA catabolic, androgen,
      xenobiotics metabolic processes in pitta, and aromatic amino acids, sphingolipid,
      and pyrimidine metabolic process in kapha Prakriti were the dominant marker
      pathways.

PMID- 29183655
TI  - Predicting Violent Behavior: What Can Neuroscience Add?
AB  - The ability to accurately predict violence and other forms of serious antisocial
      behavior would provide important societal benefits, and there is substantial
      enthusiasm for the potential predictive accuracy of neuroimaging techniques.
      Here, we review the current status of violence prediction using actuarial and
      clinical methods, and assess the current state of neuroprediction. We then
      outline several questions that need to be addressed by future studies of
      neuroprediction if neuroimaging and other neuroscientific markers are to be
      successfully translated into public policy.

PMID- 29183657
TI  - Predictive multiscale computational model of shoe-floor coefficient of friction.
AB  - Understanding the frictional interactions between the shoe and floor during
      walking is critical to prevention of slips and falls, particularly when
      contaminants are present. A multiscale finite element model of shoe-floor
      contaminant friction was developed that takes into account the surface and
      material characteristics of the shoe and flooring in microscopic and macroscopic
      scales. The model calculates shoe-floor coefficient of friction (COF) in boundary
      lubrication regime where effects of adhesion friction and hydrodynamic pressures
      are negligible. The validity of model outputs was assessed by comparing model
      predictions to the experimental results from mechanical COF testing. The
      multiscale model estimates were linearly related to the experimental results (p <
      0.0001). The model predicted 73% of variability in experimentally-measured shoe
      floor-contaminant COF. The results demonstrate the potential of multiscale finite
      element modeling in aiding slip-resistant shoe and flooring design and reducing
      slip and fall injuries.

PMID- 29183658
TI  - Value of oxyneurography, based on near infrared spectroscopy, in the diagnosis of
      carpal tunnel syndrome in comparison to provocative clinical diagnostic tests and
      nerve conduction studies.
AB  - OBJECTIVE: Evaluation of the diagnostic utility of the oxyneurography (ONG) in
      diagnosing carpal tunnel syndrome (CTS). METHODS: ONG examination of the median
      nerve was performed in 260 patients. The results were compared with nerve
      conduction studies and clinical provocative tests. RESULTS: ONG index greater
      than or equal to 62% was found in 95.18% of the patients with no or minimal Nerve
      Conduction Study (NCS) changes (1-2 according to the Padua classification) but
      only in 1.69% of the patients with advanced NCS changes (Padua 3-6). The
      sensitivity and specificity of the ONG study i.e. 95.18% and 98.31%,
      respectively, were compared with standard clinical tests: Tinel sign (61.45% and
      14.69%), Phalen test (34.94% and 45.20%), reverse Phalen test (81.93% and 34.46%)
      and carpal compression test (91.57% and 72.32%). CONCLUSIONS: ONG index lower
      than 62% was indicative of CTS. ONG has higher sensitivity and specificity then
      other clinical tests and it is an accurate and reliable method for the diagnosis
      of CTS. SIGNIFICANCE: Oxyneurography is a non-invasive, fast and safe study which
      may play role in the diagnosis of carpal tunnel syndrome.

PMID- 29183659
TI  - Are there gender differences in those diagnosed with psychogenic nonepileptic
      seizures?
AB  - OBJECTIVE: The objective of the study was to determine whether male and female
      populations of patients with psychogenic nonepileptic seizures (PNES) differ, in
      terms of demographic, social/clinical, and etiological factors as well as
      psychological measures. BACKGROUND: Psychogenic nonepileptic seizures are
      overrepresented by females; therefore, information about PNES in males is
      limited. Only a handful of studies have examined PNES and gender, and of those,
      one was a literature review and with the exception of two, most have had small
      sample sizes. Of the existing literature, differences in abuse type, psychiatric
      diagnoses, and psychometric results have been observed in the two genders.
      METHODS: This is a retrospective study of 51 consecutive males and 97 consecutive
      females with video-electroencephalogram (video-EEG) confirmed diagnosis of PNES.
      Patients were examined on demographics (age, education, working status), clinical
      (seizure frequency, trauma type: sexual, nonsexual, age of first trauma), and
      psychometric measures. The latter included the State Trait Anger Expression
      Inventory-2 (STAXI-2), Trauma Symptom Inventory-2 (TSI-2), the Coping Inventory
      for Stressful Situations (CISS), and the Quality of Life Inventory in Epilepsy-31
      (QOLIE-31). RESULTS: Women reported experiencing significantly more sexual
      traumas (p=0.007) than men. Women also endorsed significantly higher levels of
      dissociation (p=0.012) and sexual disturbances (p=0.46). In contrast, men
      reported significantly greater use of avoidance (p=0.001) as a stress coping
      strategy and higher levels of depression (p=0.006). CONCLUSIONS: Gender
      differences were identified with males reporting a significantly higher use of
      avoidance (cognitive and behavioral avoidance of stress) and depressive symptoms.
      Women exhibited significantly higher rates of sexual trauma compared with male
      counterparts. Consequently, women also had significantly higher rates of trauma
      symptomatology (dissociation and sexual disturbances) which are often observed in
      those who have been traumatized sexually. These gender distinctions may support
      different first-line treatment approaches (e.g., trauma-focused; more traditional
      cognitive behavioral therapy) depending on the most prominent symptomatology.

PMID- 29183660
TI  - Comparison of the sedative effects of nalbuphine and butorphanol, alone or in
      combination with acepromazine in dogs.
AB  - OBJECTIVE: To compare sedation and effects on heart rate (HR), mean arterial
      pressure (MAP) and respiratory rate (fR) of nalbuphine and butorphanol, alone or
      combined with acepromazine in dogs. STUDY DESIGN: Prospective, randomized
      experimental trial. ANIMALS: Eight healthy Beagle dogs, aged (mean +/- standard
      deviation) 3.4 +/- 0.5 years and weighing 11.0 +/- 1.3 kg. METHODS: Each dog was
      treated four times: physiological saline (1 mL) combined with nalbuphine (0.5 mg
      kg-1; SAL-NAL) or butorphanol (0.15 mg kg-1; SAL-BUT), and acepromazine (0.05 mg
      kg-1) combined with nalbuphine (0.5 mg kg-1; ACP-NAL) or butorphanol (0.15 mg kg
      1; ACP-BUT), intravenously (IV). The degree of sedation, assessed by a numeric
      descriptive scale (NDS) and simple numerical scale (SNS), HR, MAP, fR and rectal
      temperature (RT), were recorded before and 20 minutes after administration of
      saline or acepromazine, then 15, 30, 60, 90 and 120 minutes after nalbuphine or
      butorphanol. Values were compared with baseline and among treatments. RESULTS:
      Mild sedation was recorded for SAL-NAL and SAL-BUT, and moderate sedation for ACP
      NAL and ACP-BUT. NDS and SNS scores were higher for SAL-BUT and ACP-BUT at some
      time points when compared with SAL-NAL and ACP-NAL, respectively (p < 0.001). HR
      was lower in ACP-NAL than in ACP-BUT at 120 minutes and fR was lower in SAL-BUT
      than in SAL-NAL at 30 and 120 minutes (p < 0.05). RT was lower in SAL-BUT (37.5
      +/- 0.5  degrees C) compared with SAL-NAL (38.0 +/- 0.5  degrees C) at 60-120
      minutes (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol promoted a
      higher sedative effect than nalbuphine when alone and combined with acepromazine.
      IV administration of nalbuphine or butorphanol, with or without acepromazine, at
      the doses studied, resulted in minimal decreases in MAP, HR, fR and RT.

PMID- 29183661
TI  - Design, synthesis and evaluation against Mycobacterium tuberculosis of azole
      piperazine derivatives as dicyclotyrosine (cYY) mimics.
AB  - Three series of azole piperazine derivatives that mimic dicyclotyrosine (cYY),
      the natural substrate of the essential Mycobacterium tuberculosis cytochrome P450
      CYP121A1, were prepared and evaluated for binding affinity and inhibitory
      activity (MIC) against M. tuberculosis. Series A replaces one phenol group of cYY
      with a C3-imidazole moiety, series B includes a keto group on the hydrocarbon
      chain preceding the series A imidazole, whilst series C explores replacing the
      keto group of the piperidone ring of cYY with a CH2-imidazole or CH2-triazole
      moiety to enhance binding interaction with the heme of CYP121A1. The series
      displayed moderate to weak type II binding affinity for CYP121A1, with the
      exception of series B 10a, which displayed mixed type I binding. Of the three
      series, series C imidazole derivatives showed the best, although modest,
      inhibitory activity against M. tuberculosis (17d MIC = 12.5 MUg/mL, 17a 50
      MUg/mL). Crystal structures were determined for CYP121A1 bound to series A
      compounds 6a and 6b that show the imidazole groups positioned directly above the
      haem iron with binding between the haem iron and imidazole nitrogen of both
      compounds at a distance of 2.2 A. A model generated from a 1.5 A crystal
      structure of CYP121A1 in complex with compound 10a showed different binding modes
      in agreement with the heterogeneous binding observed. Although the crystal
      structures of 6a and 6b would indicate binding with CYP121A1, the binding assays
      themselves did not allow confirmation of CYP121A1 as the target.

PMID- 29183662
TI  - Bisindolylmethane thiosemicarbazides as potential inhibitors of urease: Synthesis
      and molecular modeling studies.
AB  - Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H
      NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed
      outstanding urease inhibitory potentials with IC50 values ranging between 0.14 +/
      0.01 to 18.50 +/- 0.90 MUM when compared with the standard inhibitor thiourea
      having IC50 value 21.25 +/- 0.90 MUM. Among the series, analog 9 (0.14 +/- 0.01
      MUM) with di-chloro substitution on phenyl ring was identified as the most potent
      inhibitor of urease. The structure activity relationship has been also
      established on the basis of binding interactions of the active analogs. These
      binding interactions were identified by molecular docking studies.

PMID- 29183663
TI  - Peptide therapeutics for the treatment of gastrointestinal disorders.

PMID- 29183664
TI  - Distal urethral plate adhesions: New anatomical perspective in hypospadias.
AB  - INTRODUCTION: We found midline epithelial adhesions in the glandar urethral plate
      in patients with hypospadias. After dissolution, a blind epithelized channel
      becomes visualized inside of the plate pointing to immature embryonic
      luminization. In addition it reveals that the epithelized surface of the distal
      urethral plate is larger than previously considered. OBJECTIVE: To determine the
      incidence and extent of these new anatomical details of urethral plate in
      hypospadias patients. METHODS: We prospectively assessed the detailed anatomy of
      the urethral plate in 72 consecutive patients with hypospadias. We recorded the
      presence of adhesions in the middle of the glandar urethral groove that can be
      easily dissoluted (dissolution line - D-line). We recorded the plate width before
      and after D-line dissolution, the presence of the hidden blind channel at
      continuation of D-line (channel type-A) and of the visible blind channel between
      D-line and urethral hypospadiac meatus (type-B) (Figure). In 62 patients, where
      the urethral plate tubularization was considered (Duplay, TIP), septs between
      channels were opened in the midline and a final width of the plate was measured
      by rolling the plate around a tube. RESULTS: Midline adhesions (D-line) were
      found in all 72 patients. Mean length of D-line was 5.13 +/- O.17 mm. Mean plate
      width before dissolution was 5.9 +/- 0.15 mm, and after dissolution 7.8 +/- 0.16
      mm. A blind channel of type A was detected in 22 patients (31%), type B in 24
      (33%), type A and B in 16 (22%), and none in 10 patients (14%). Mean final plate
      width after D-line dissolution and opening of septs between channels in 62
      patients with urethral plate tubularization was 8.7 +/- 0.15 mm. DISCUSSION: The
      main contribution of our study is a new perspective of distal urethral plate
      anatomy that enables enlargement of the epithelized surface of the distal
      urethral plate by dissolution of the preexisting epithelized groove and opening
      of epithelized channels within the plate. To the best of our knowledge, this
      anatomical anomaly has not been described previously. CONCLUSIONS: The distal
      urethral plate of all hypospadias patients is partially "folded" in the midline
      by epithelial adhesions of different depth and extent that may be easily
      dissoluted. In half of the patients (53%) the "folded" part of the plate
      continues proximally as a blind channel inside the urethral plate (type A
      channel). Opening of these structures together with the well-known urethral plate
      pits (type B channel) helps augment the width and the overall epithelized surface
      of the distal urethral plate.

PMID- 29183665
TI  - Stereochemical Divergence of Polyprenol Phosphate Glycosyltransferases.
AB  - In the three domains of life, lipid-linked glycans contribute to various cellular
      processes ranging from protein glycosylation to glycosylphosphatidylinositol
      anchor biosynthesis to peptidoglycan assembly. In generating many of these
      glycoconjugates, phosphorylated polyprenol-based lipids are charged with single
      sugars by polyprenol phosphate glycosyltransferases. The resultant substrates
      serve as glycosyltransferase donors, complementing the more common nucleoside
      diphosphate sugars. It had been accepted that these polyprenol phosphate
      glycosyltransferases acted similarly, given their considerable sequence homology.
      Recent findings, however, suggest that matters may not be so simple. In this
      Opinion we propose that the stereochemistry of sugar addition by polyprenol
      phosphate glycosyltransferases is not conserved across evolution, even though the
      GT-A fold that characterizes such enzymes is omnipresent.

PMID- 29183666
TI  - Microembolism of single cortical arterioles can induce spreading depression and
      ischemic injury; a potential trigger for migraine and related MRI lesions.
AB  - Increasing epidemiological evidence suggests an association between migraine with
      aura (MA) and cardiovascular events. There is experimental as well as clinical
      evidence implying cerebral microembolism as a potential trigger for MA attacks.
      Microembolism may also account for some of the ischemic MRI lesions more commonly
      observed in MA than in general population. Limited size of clinically-silent MRI
      lesions suggests isolated occlusion of a small vessel. However, it is not known
      whether selective thrombosis of a small arteriole (e.g. single mouse penetrating
      arteriole - PA), can induce cortical spreading depression (CSD), the putative
      cause of migraine aura and, hence, trigger an MA attack. For this, we mimiced
      thrombosis of a small vessel caused by microembolism by selectively occluding a
      PA just before diving into the cortex (radius; 10-25 um) in the mouse. Clotting
      was induced with FeCl3 applied focally over the PA by a glass micropipette for 3
      min. DC potential changes were recorded and the alterations in cortical blood
      flow were monitored by laser speckle contrast imaging. Mice were kept alive for 1
      4 weeks and brain sections were stained with H&E or luxol-fast blue to evaluate
      changes induced by PA occlusion. We found that single PA occlusion consistently
      triggered a CSD originating from the tissue around the PA soon after occlusion
      and induced delayed, small ischemic lesions within territory of the affected
      vessel a few weeks later. These findings suggest that cerebral microembolism can
      lead to MA attacks and may account for some of the silent brain lesions.

PMID- 29183667
TI  - Early prediction of persistent organ failure by serum apolipoprotein A-I and high
      density lipoprotein cholesterol in patients with acute pancreatitis.
AB  - BACKGROUND: Early identification of acute pancreatitis (AP) patients at high-risk
      of developing persistent organ failure (persistent OF) is a vital clinical goal.
      This research intends to assess the ability of apolipoprotein A-I (APO A-I) and
      high-density lipoprotein cholesterol (HDL-C) to predict persistent OF. METHODS:
      Between January 2011 and September 2016, a total of 102 adult AP patients with
      organ failure, local complications or deterioration of former comorbidities
      disease during hospitalization were included in this study retrospectively. Serum
      lipids were tested and computed the correlation with clinical outcomes or scoring
      systems. The AUCs to predict persistent OF were also calculated and compared with
      each other. RESULTS: Serum APO A-I and HDL-C levels were negatively associated
      with scoring systems. Meanwhile, serum lipids were negatively correlated with
      poor clinical outcomes. The AUCs of APO A-I, HDL-C, the combination of APO A-I
      and BISAP, or the combination of APO A-I and MCTSI to predict persistent OF among
      Moderately severe acute pancreatitis (MSAP) and Severe acute pancreatitis (SAP)
      patients were 0.886, 0.811, 0.912, and 0.900 or among those with organ failure
      were 0.915, 0.859, 0.933, and 0.933, respectively. CONCLUSIONS: The
      concentrations of APO A-I, HDL-C, and the combinations of APO A-I and scoring
      systems have high predictive value to predict persistent OF.

PMID- 29183668
TI  - Core-shell magnetic molecularly imprinted polymers used rhodamine B
      hydroxyproline derivate as template combined with in situ derivatization for the
      specific measurement of L-hydroxyproline.
AB  - In this work, a novel core-shell magnetic molecularly imprinted polymers (MMIPs)
      for the measurement of L-Hydroxyproline (Hyp) in dairy products was prepared. The
      derivative of Hyp using N-hydroxysuccinimidyl rhodamine B ester (RBS) as
      derivatization reagent was employed as template to prepare RBS-Hyp-MMIPs
      (Fe3O4@MIPs for RBS-Hyp). A new analytical procedure of in situ derivatization
      with MMIPs (ISD-MMIPs) has been developed for the specific extraction and
      determination of Hyp in dairy products by ultra high performance liquid
      chromatography tandem mass spectrometry. The RBS-Hyp-MMIPs was characterized by
      fourier transform infrared spectrometer and transmission electron microscopy, and
      evaluated by adsorption experiments. The adsorption process followed Langumuir
      adsorption isotherm with maximum adsorption capacity of RBS-Hyp on RBS-Hyp-MMIPs
      at 96 mg/g. In addition, RBS-Hyp-MMIPs showed a short equilibrium time (15.0
      min), rapid magnetic separation (5 s) and high stability (retained 95.3% after
      six cycles). Under the optimized conditions, good linearity was observed with the
      limits of detection (S/N > 3) and limits of quantification (S/N > 10) at 0.1 and
      0.5 ng/mL, respectively. On account of the specific extraction performance of RBS
      Hyp-MMIPs, not any interference peak from real sample matrix was observed in the
      chromatograms of milk powder, liquid milk and milk drink. The proposed procedure
      was successfully applied for selective determination of Hyp from dairy products
      with satisfactory validation results, which is of great significance to food
      safety.

PMID- 29183669
TI  - Quantification of more than 150 micropollutants including transformation products
      in aqueous samples by liquid chromatography-tandem mass spectrometry using
      scheduled multiple reaction monitoring.
AB  - A direct injection, multi residue analytical method separated in two
      chromatographic runs was developed utilizing scheduled analysis to simultaneously
      quantify 154 compounds, 84 precursors and 70 transformation products
      (TPs)/metabolites. Improvements in the chromatographic data quality, sensitivity
      and reproducibility were achieved by scheduling the analysis of each analyte into
      pre-determined retention time windows. This study shows the influence of the scan
      time on the dwell time and the number of data points per peak as well as the
      effect on the precision of analysis. Lowering the scan time decreased dwell time
      to a minimal value, however, this had no negative effects on the precision.
      Increasing the number of data points per peak by decreasing the scan time led to
      more accurate peak shapes. A final set of parameters was chosen to obtain a
      minimum of 10 data points per peak to guarantee accurate peak shapes and thus
      reproducibility of analysis. A validation of the method was performed for
      different water matrices yielding very good linearity for all substances, with
      limits of quantification mainly in the lower to mid ng/L-range and recoveries
      mainly between 70 and 125% for surface water, bank filtrate as well as influents
      and effluents of wastewater treatment plants. The analysis of environmental
      samples and wastewater revealed the occurrence of selected precursors and TPs in
      all analyzed matrices: 95% of the compounds in the target list could be
      quantified in at least one sample. The relevance of TPs and metabolites such as
      valsartan acid and clopidogrel acid was also confirmed by their detection in all
      aqueous matrices. Wastewater indicators such as acesulfame and diclofenac were
      detected at elevated concentrations as well as substances such as oxipurinol
      which so far were not in the focus of monitoring programs. The developed method
      can be used for rapid analysis of various water matrices without any sample
      enrichment and can aid the assessment of water quality and water treatment
      processes.

PMID- 29183670
TI  - Using glass-graded zirconia to increase delamination growth resistance in
      porcelain/zirconia dental structures.
AB  - OBJECTIVE: Porcelain fused to zirconia (PFZ) restorations are widely used in
      prosthetic dentistry. However, their tendency to delaminate along the P/Z
      interface remains a practical problem so that assessing and improving the
      interfacial strength are important design aspects. This work examines the effect
      of modifying the zirconia veneering surface with an in-house felspathic glass on
      the interfacial fracture resistance of fused P/Z. METHODS: Three material systems
      are studied: porcelain fused to zirconia (control) and porcelain fused to glass
      graded zirconia with and without the presence of a glass interlayer. The
      specimens were loaded in a four-point-bend fixture with the porcelain veneer in
      tension. The evolution of damage is followed with the aid of a video camera. The
      interfacial fracture energy GC was determined with the aid of a FEA, taking into
      account the stress shielding effects due to the presence of adjacent channel
      cracks. RESULTS: Similarly to a previous study on PFZ specimens, the fracture
      sequence consisted of unstable growth of channel cracks in the veneer followed by
      stable cracking along the P/Z interface. However, the value of GC for the graded
      zirconia was approximately 3 times that of the control zirconia, which is due to
      the good adhesion between porcelain and the glass network structure on the
      zirconia surface. SIGNIFICANCE: Combined with its improved bonding to resin-based
      cements, increased resistance to surface damage and good esthetic quality, graded
      zirconia emerges as a viable material concept for dental restorations.

PMID- 29183671
TI  - Effect of titania content and biomimetic coating on the mechanical properties of
      the Y-TZP/TiO2 composite.
AB  - OBJECTIVE: To investigate the effect of titania addition (0, 10 and 30mol%) on
      the microstructure, relative density, Young's modulus (E), Poisson's ratio
      (upsilon), mechanical properties (flexural strength, sigmaf, and Weibull modulus,
      m) of a Y-TZP/TiO2 composite. The effect of the presence of a biomimetic coating
      on the microstructure and mechanical properties was also evaluated. METHODS: Y
      TZP (3mol% of yttria) and Y-TZP/TiO2 composite (10 or 30mol% of titania) were
      synthesized by co-precipitation. The powders were pressed and sintered at 1400
      degrees C/2h. The surfaces, with and without biomimetic coating, were
      characterized by X-ray diffraction analysis and scanning electron microscopy. The
      relative density was measured by the Archimedes' principle. E and upsilon were
      measured by ultrasonic pulse-echo method. For the mechanical properties the
      specimens (n=30 for each group) were tested in a universal testing machine.
      RESULTS: Titania addition increased the grain size of the composite and caused a
      significant decrease in the flexural strength (in MPa, control 815.4a; T10 455.7b
      and T30 336.0c), E (in GPa, control 213.4a; T10 155.8b and T30 134.0c) and
      relative density (control 99.0%a; T10 94.4%c and T30 96.3%b) of the Y-TZP/TiO2
      composite. The presence of 30% titania caused substantial increase in m and
      upsilon. Biomimetic coating did not affect the mechanical properties of the
      composite. SIGNIFICANCE: The Y-TZP/TiO2 composite coated with a layer of CaP has
      great potential to be used as implant material. Although addition of titania
      affected the properties of the composite, the application of a biomimetic coating
      did not jeopardize its reliability.

PMID- 29183672
TI  - Bisphenol A release from an orthodontic resin composite: A GC/MS and LC/MS study.
AB  - OBJECTIVES: First, to analyse the in vitro release of BPA and Bis-GMA from an
      orthodontic resin composite (Transbond XT, 3M Unitek), stored in various
      conditions, by gas chromatography/mass spectrometry (GC/MS) and liquid
      chromatography/mass spectrometry (LC/MS); then to extrapolate the data to the
      clinical situation. Secondly, to explore the thermal stability of Bis-GMA.
      METHODS: Cylinders of resin composite were prepared and stored according to 3
      different protocols: (1) they were light-cured 20s, then placed in artificial
      saliva; (2) they were light-cured 2s, then placed in acetonitrile; (3) they were
      light-cured 2s, then placed in methanol. For each group, BPA and Bis-GMA release
      were determined with GC/MS and/or LC/MS at least after one week. Besides, 120
      brackets (10 of each type) were bonded over metal teeth, then debonded, and the
      weight and the surface of resin composite residues were measured. BPA and Bis-GMA
      release of adhesive residues were extrapolated from the data obtained with the
      cylinders. Besides, BPA release from a heated Bis-GMA solution was measured.
      RESULTS: With GC/MC, BPA was detected in all samples. With LC/MS, BPA was
      detected only from samples immersed in MeOH; Bis-GMA was detected, in varying
      amount according to the extraction media and the light-curing time. BPA was found
      after heating of the Bis-GMA solution. SIGNIFICANCE: Contamination risk and the
      heat applied in GC/MS may overestimate the BPA release from resin composite.
      Based on the LC/MS results, the risk of BPA release after orthodontic bonding
      would be more than 42000 times lower than the TDI for a 30-kg child.

PMID- 29183673
TI  - Effect of tribochemical treatments and silane reactivity on resin bonding to
      zirconia.
AB  - OBJECTIVE: The aim of the study was to assess the roughness, structure and bond
      strength with zirconia of four grit-blasting treatments combined with three
      silane types, the reactivity of which was evaluated, as well. METHODS: The grit
      blasted treatments performed on zirconia (Lava) were alumina (ALU), CoJet (COJ),
      SilJet (SLJ) and SilJet Plus (SJP, with silica-encapsulated silane). The other
      two silanes selected were the S-Bond (SB, prehydrolyzed) and Clearfil Ceramic
      Primer Plus (CP, prehydrolyzed with 10-MDP). The activity of the silanols in the
      silanes was evaluated by FTIR spectroscopy. Optical profilometry and Raman
      microspectroscopy were used for the assessment of roughness (Sa, Sz, Sdr
      parameters) and structure (monoclinic volume-Vm) of zirconia, before (REF) and
      after grit-blasting, and a shear bond strength (SBS) with a flowable resin
      composite, for the investigation of the bonding capacity of the treatments.
      RESULTS: Only SB demonstrated reactive silanols. CP and the SJP silanes were
      mostly in a polymerized siloxane state. Roughness was increased after grit
      blasting as follows: ALU>SLJ,SJP>COJ>REF (Sa,Sz) and ALU>SLJ,COJ,SJP>REF (Sdr).
      ALU demonstrated the highest Vm (7.52%) from all other treatments (4.16-4.81%)
      and the REF (0%). COJ and SLJ showed the highest SBS (14-15.94MPa) regardless of
      the silane type used. SJP showed no significant differences from SLJ-SB and COJ
      SB. Weibull analysis showed a reliability (beta) ranking of COJ, SJP, SLJ, ALU
      CP>ALU-SB>REF and a characteristic life (eta) ranking of COJ, SLJ, >=SLJ-SB, SJP,
      ALU>=ALU-SB,REF-CP>REF-SB. SIGNIFICANCE: The reactivity of the silanes used
      showed great variations to support a predictable effect in all treatments. CP
      with deactivated silanols demonstrated a) the most reliable and strongest
      treatment with a silica-rich powder (COJ), despite the lowest Sa,Sz substrate
      values and b) high strength with a low-silica powder (SLJ) with higher Sa,Sz
      substrate values. Therefore, it may be concluded that 10-MDP greatly contributes
      to the bonding mechanism of the silane containing primers.

PMID- 29183674
TI  - Effects of different sterilization methods on surface characteristics and biofilm
      formation on zirconia in vitro.
AB  - OBJECTIVE: The current laboratory study was to investigate the effect of
      different sterilization treatments on surface characteristics of zirconia, and
      biofilm formation on zirconia surface after exposure to these sterilization
      treatments. METHODS: Commercially available zirconia discs (Cerconbase, Degu
      Dent, Hanau, Germany) were prepared and polished to the same value of surface
      roughness. The discs were treated with one of the following sterilization methods
      steam autoclave sterilization, dry heat sterilization, ultraviolet C (UVC)
      irradiation, and gamma (gamma) ray irradiation. The characteristics of zirconia
      surfaces were evaluated by scanning electron microscopy (SEM), surface roughness,
      surface free energy (SFE), X-ray photoelectron spectroscopy (XPS), and X-ray
      diffraction (XRD) measurements. Then, Staphylococcus aureus (S.a.) and
      Porphyromonas gingivalis (P.g.) bacteria were used and cultured on the respective
      sterilized zirconia surfaces. The amount of biofilm formation on zirconia surface
      was quantified by colony forming unit (CFU) counts. RESULTS: Significant
      modifications were detected on the colour and SFE of zirconia. The colour of
      zirconia samples after UVC irradiation became light yellow whilst dark brown
      colour was observed after gamma ray irradiation. Moreover, UVC and gamma ray
      irradiation increased the hydrophilicity of zirconia surface. Overall, dry heat
      sterilized samples showed the significantly lowest amount of bacteria growth on
      zirconia, while UVC and gamma ray irradiation resulted in the highest.
      SIGNIFICANCE: It is evident that various sterilization methods could change the
      surface which contribute to different biofilm formation and colour on zirconia.

PMID- 29183675
TI  - Red nucleus interleukin-6 participates in the maintenance of neuropathic pain
      through JAK/STAT3 and ERK signaling pathways.
AB  - We previously reported that interleukin-6 (IL-6) in the red nucleus (RN) is up
      regulated at 3weeks after spared nerve injury (SNI), and plays facilitated role
      in the later maintenance of neuropathic pain. The current study aimed to reveal
      the roles of different signaling pathways, including Janus kinase/signal
      transducer and activator of transcription 3 (JAK/STAT3), extracellular signal
      regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated
      protein kinase (MAPK) and phosphatidylinositide 3-kinase/protein kinase B
      (PI3K/AKT), in RN IL-6-mediated pain modulation. In accord with the increase of
      IL-6 in the RN following SNI, the protein levels of phospho-STAT3 (p-STAT3), p
      ERK and p-JNK were also up-regulated in the RN contralateral to the nerve injury
      side at 3weeks after SNI. The increases of p-STAT3 and p-ERK (but not p-JNK) were
      associated with IL-6 and could be blocked by anti-IL-6 antibody. Microinjection
      of JAK2 inhibitor AG490, ERK inhibitor PD98059 and also JNK inhibitor SP600125
      into the RN significantly increased the paw withdrawal threshold (PWT) and
      alleviated SNI-induced mechanical allodynia. Further studies showed that
      microinjection of recombinant rat IL-6 (rrIL-6, 20ng) into the RN of normal rats
      significantly decreased the PWT of rats and increased the local protein levels of
      p-STAT3 and p-ERK, but not p-JNK. Pre-treatment with AG490 and PD98059 could
      prevent IL-6-induced mechanical allodynia. Whereas, p-p38 MAPK and p-AKT did not
      show any expression changes in the RN of rats with SNI or rats treated with rrIL
      6. These results suggest that RN IL-6 participates in the later maintenance of
      SNI-induced neuropathic pain and plays facilitated role through activating
      JAK/STAT3 and ERK signaling pathways.

PMID- 29183677
TI  - Contribution of 18F-FDG PET/CT in the diagnosis of recurrence of Takayasu's
      arteritis.

PMID- 29183676
TI  - Depolarization and electrical stimulation enhance in vitro and in vivo sensory
      axon growth after spinal cord injury.
AB  - Activity dependent plasticity is a key mechanism for the central nervous system
      (CNS) to adapt to its environment. Whether neuronal activity also influences
      axonal regeneration in the injured CNS, and whether electrical stimulation (ES)
      can activate regenerative programs in the injured CNS remains incompletely
      understood. Using KCl-induced depolarization, in vivo ES followed by ex-vivo
      neurite growth assays and ES after spinal cord lesions and cell grafting, we
      aimed to identify parameters important for ES-enhanced neurite growth and axonal
      regeneration. Using cultures of sensory neurons, neurite growth was analyzed
      after KCl-induced depolarization for 1-72h. Increased neurite growth was detected
      after short-term stimulation and after longer stimulation if a sufficient delay
      between stimulation and growth measurements was provided. After in vivo ES (20Hz,
      2* motor threshold, 0.2ms, 1h) of the intact sciatic nerve in adult Fischer344
      rats, sensory neurons showed a 2-fold increase in in vitro neurite length one
      week later compared to sham animals, an effect not observed one day after ES.
      Longer ES (7h) and repeated ES (7days, 1h each) also increased growth by 56-67%
      one week later, but provided no additional benefit. In vivo growth of dorsal
      column sensory axons into a graft of bone marrow stromal cells 4weeks after a
      cervical spinal cord lesion was also enhanced with a single post-injury 1h ES of
      the intact sciatic nerve and was also observed after repeated ES without inducing
      pain-like behavior. While ES did not result in sensory functional recovery, our
      data indicate that ES has time-dependent influences on the regenerative capacity
      of sensory neurons and might further enhance axonal regeneration in combinatorial
      approaches after SCI.

PMID- 29183678
TI  - [Description of contributing factors in adverse events related to patient safety
      and their preventability].
AB  - OBJECTIVE: To assess the extent of healthcare related adverse events (AEs), their
      effect on patients, and their seriousness. To analyse the factors leading to the
      development of AEs, their relationship with the damage caused, and their degree
      of preventability. DESIGN: Retrospective descriptive study. LOCATION: Porrino,
      Pontevedra, Spain, Primary Care Service, from January-2014 to April-2016.
      PARTICIPANTS AND/OR CONTEXT: Reported AEs were entered into the Patient Safety
      Reporting and Learning System (SiNASP). METHOD: The variables measured were: Near
      Incident (NI) an occurrence with no effect or harm on the patient; Adverse Event
      (AE) an occurrence that affects or harms a patient. The level of harm is
      classified as minimal, minor, moderate, critical, and catastrophic.
      Preventability was classified as little evidence of being preventable, 50%
      preventable, and sound evidence of being preventable. DATA ANALYSIS: percentages
      and Chi-squared test for qualitative variables; P<.05 with SPSS.15. DATA SOURCE:
      SiNASP. Ethical considerations: approved by the Research Ethics Committee
      (2016/344). RESULTS: There were 166 recorded AEs (50.6% in males, and 46.4% in
      women. The mean age was 60.80years). Almost two-thirds 62.7% of AEs affected the
      patient, with 45.8% causing minimal damage, while 2.4% caused critical damages.
      Healthcare professionals were a contributing factor in 71.7% of the AEs, with the
      trend showing that poor communication and lack of protocols were related to the
      damage caused. Degree of preventability: 96.4%. CONCLUSIONS: Most AEs affected
      the patient, and were related to medication, diagnostic tests, and laboratory
      errors. The level of harm was related to communication problems, lack of, or
      deficient, protocols and a poor safety culture.

PMID- 29183679
TI  - Angiographic perfusion imaging of intracranial stenting.
AB  - Two-dimensional angiographic perfusion imaging (2DAP) is a new technique
      permitting perfusion imaging during angiography, and has been used to study
      cerebral vasospasm. Here we report our experience with this technique following
      angioplasty and stent placement in a patient with symptomatic and medically
      refractory stenosis of the right supraclinoid internal carotid artery. We found
      that intraprocedural angiographic perfusion imaging provided real-time and
      objective evidence of improved cerebral perfusion during intervention. Following
      treatment, the patient remains symptom-free at last follow-up.

PMID- 29183680
TI  - Drug therapy for chronic subdural hematoma: Bench to bedside.

PMID- 29183681
TI  - Effects of repeated nerve injuries at different time intervals on functional
      recovery and nerve innervation.
AB  - Effects of repeated nerve injuries on functional recovery and nerve innervation
      were examined in rodents. Crush injuries of the sciatic nerve were inflicted on
      adult rats and repeated twice or thrice at different time intervals of 1, 2, 3,
      and 4 weeks. Motor function was assessed by the static sciatic index at 1, 7, 14,
      21, 28, 35, 42, 49, and 56 days after the final crush. The rates of nerve
      innervation of the tibialis anterior muscle, a main muscle innervated by the
      common peroneal nerve, were evaluated by the quantification of betaIII-tubulin
      positive nerve terminals and alpha-bungarotoxin-positive acetylcholine receptors
      21 and 56 days after the final crush of triple nerve injuries at 1-, 2-, 3-, and
      4-week intervals. Compared with single nerve crush injury, delayed recovery of
      motor function was observed in repeated crush injuries. In addition, recoveries
      in the triple crush groups were slower than those in the double crush groups. The
      rates of reinnervation were lower in the triple crush groups than in the single
      crush groups, both at 21 days (single: 59.7%; triple: 54.1%-56.1%) and 56 days
      (single: 88.8%; triple: 72.5%-83.0%) after the final crush, except in the groups
      with 1-week (triple: 73.8%) and 2-week (triple: 70.5%) intervals at 21 days after
      the final crush. We concluded that the recovery of motor function was delayed
      according to the number of repetitions of crush injuries, and that the rates of
      nerve innervation were still low in the triple crush groups 8 weeks after the
      final crush.

PMID- 29183682
TI  - Treatment of a glioblastoma multiforme dural metastasis with stereotactic
      radiosurgery: A case report and select review of the literature.
AB  - Glioblastoma multiforme (GBM) is a primary brain neoplasm accounting for
      approximately 75% of all high grade gliomas. It is diffusely infiltrative and
      exhibits rapid proliferation with a poor overall prognosis. Maximum surgical
      resection and postoperative radiotherapy, accompanied by concurrent and adjuvant
      temozolomide chemotherapy, remain the standard of care without major therapeutic
      advances over the past 10 years. Herein, we present the case of a 64-year-old
      Caucasian male with a GBM who subsequently developed a left frontal dural
      metastasis, subsequently treated with stereotactic radiosurgery (20 Gy in 1
      fraction). With six month follow-up, the patient showed near complete resolution
      of his dural metastases and no overall change in neurological symptoms or side
      effects following radiosurgery. Due to the paucity of clinical literature
      regarding dural metastases from GBM, its optimal treatment remains unknown. While
      the role of SRS has yet to be defined in this setting, here we provide evidence
      suggesting its overall efficacy in the treatment of select dural GBM metastases.

PMID- 29183683
TI  - Cellular diversity of the somatosensory cortical map plasticity.
AB  - Sensory maps are representations of the sensory epithelia in the brain. Despite
      the intuitive explanatory power behind sensory maps as being neuronal precursors
      to sensory perception, and sensory cortical plasticity as a neural correlate of
      perceptual learning, molecular mechanisms that regulate map plasticity are not
      well understood. Here we perform a meta-analysis of transcriptional and
      translational changes during altered whisker use to nominate the major molecular
      correlates of experience-dependent map plasticity in the barrel cortex. We argue
      that brain plasticity is a systems level response, involving all cell classes,
      from neuron and glia to non-neuronal cells including endothelia. Using molecular
      pathway analysis, we further propose a gene regulatory network that could couple
      activity dependent changes in neurons to adaptive changes in neurovasculature,
      and finally we show that transcriptional regulations observed in major brain
      disorders target genes that are modulated by altered sensory experience. Thus,
      understanding the molecular mechanisms of experience-dependent plasticity of
      sensory maps might help to unravel the cellular events that shape brain
      plasticity in health and disease.

PMID- 29183684
TI  - Age-related changes in the neural networks supporting semantic cognition: A meta
      analysis of 47 functional neuroimaging studies.
AB  - Semantic cognition is central to understanding of language and the world and,
      unlike many cognitive domains, is thought to show little age-related decline. We
      investigated age-related differences in the neural basis of this critical
      cognitive domain by performing an activation likelihood estimation (ALE) meta
      analysis of functional neuroimaging studies comparing young and older people. On
      average, young people outperformed their older counterparts during semantic
      tasks. Overall, both age groups activated similar left-lateralised regions.
      However, older adults displayed less activation than young people in some
      elements of the typical left-hemisphere semantic network, including inferior
      prefrontal, posterior temporal and inferior parietal cortex. They also showed
      greater activation in right frontal and parietal regions, particularly those held
      to be involved in domain-general controlled processing, and principally when they
      performed more poorly than the young. Thus, semantic processing in later life is
      associated with a shift from semantic-specific to domain-general neural
      resources, consistent with the theory of neural dedifferentiation, and a
      performance-related reduction in prefrontal lateralisation, which may reflect a
      response to increased task demands.

PMID- 29183685
TI  - Latest progress in craniofacial identification: 17th Biennial Meeting of the
      International Association of Craniofacial Identification (IACI), Brisbane, 15-19
      July 2017.

PMID- 29183689
TI  - Participation and retention can be high in randomized controlled trials targeting
      underserved populations: a systematic review and meta-analysis.

PMID- 29183687
TI  - Functional role for cortical-striatal circuitry in modulating alcohol self
      administration.
AB  - The cortical-striatal brain circuitry is heavily implicated in drug-use. As such,
      the present study investigated the functional role of cortical-striatal circuitry
      in modulating alcohol self-administration. Given that a functional role for the
      nucleus accumbens core (AcbC) in modulating alcohol-reinforced responding has
      been established, we sought to test the role of cortical brain regions with
      afferent projections to the AcbC: the medial prefrontal cortex (mPFC) and the
      insular cortex (IC). Long-Evans rats were trained to self-administer alcohol (15%
      alcohol (v/v)+2% sucrose (w/v)) during 30 min sessions. To test the functional
      role of the mPFC or IC, we utilized a chemogenetic technique (hM4Di-Designer
      Receptors Activation by Designer Drugs) to silence neuronal activity prior to an
      alcohol self-administration session. Additionally, we chemogenetically silenced
      mPFC->AcbC or IC->AcbC projections, to investigate the role of cortical-striatal
      circuitry in modulating alcohol self-administration. Chemogenetically silencing
      the mPFC decreased alcohol self-administration, while silencing the IC increased
      alcohol self-administration, an effect absent in mCherry-Controls. Interestingly,
      silencing mPFC->AcbC projections had no effect on alcohol self-administration. In
      contrast, silencing IC->AcbC projections decreased alcohol self-administration,
      in a reinforcer-specific manner as there was no effect in rats trained to self
      administer sucrose (0.8%, w/v). Additionally, no change in self-administration
      was observed in the mCherry-Controls. Together these data demonstrate the complex
      role of the cortical-striatal circuitry while implicating a role for the insula
      striatal circuit in modulating ongoing alcohol self-administration.

PMID- 29183686
TI  - Neurocognitive dysfunction following repeated binge-like self-administration of
      the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV).
AB  - Synthetic cathinones, frequently referred to as "bath salts", have significant
      abuse potential, and recent evidence suggests that these novel psychoactive
      substances can also produce cognitive deficits as well as cytotoxic effects.
      However, most of these latter findings have been obtained either using high
      concentrations in vitro or following non-contingent high dose administration in
      vivo. The present study utilized a model of long-term voluntary binge-like self
      administration to determine potential detrimental effects of synthetic cathinones
      on cognitive function and their known underlying neural circuits, collectively
      referred to as neurocognitive dysfunction. Male Sprague-Dawley rats were allowed
      to self-administer the cocaine-like synthetic cathinone 3,4
      methylenedioxypyrovalerone (MDPV, 0.03 mg/kg/infusion i.v.) in 96-hr sessions, or
      saline as a control. A total of five 96-hr sessions were conducted, each
      separated by 3 days of abstinence in the home cage. Three weeks following the
      last 96-hr session, animals underwent assessment of cognitive function using
      spatial object recognition (SOR) and novel object recognition (NOR) tasks, after
      which brains were harvested and assessed for neurodegeneration using FluoroJade C
      (FJC). Compared to animals self-administering saline, animals self-administering
      MDPV demonstrated (1) robust drug intake that escalated over time, (2) deficits
      in NOR but not SOR, and (3) neurodegeneration in the perirhinal and entorhinal
      cortices. These results indicate that repeated binge-like intake of MDPV can
      induce neurocognitive dysfunction. In addition, utilization of rodent models of
      extended binge-like intake may provide insight into potential mechanisms and/or
      approaches to prevent or reverse the detrimental effects of abused substances on
      cognitive and neurobiological functioning. This article is part of the Special
      Issue entitled 'Designer Drugs and Legal Highs.'

PMID- 29183688
TI  - An exploratory investigation of brain-selective estrogen treatment in males using
      a mouse model of Alzheimer's disease.
AB  - Estrogens are neuroprotective, and studies suggest that they may mitigate the
      pathology and symptoms of Alzheimer's disease (AD) in female models. However,
      central estrogen effects have not been examined in males in the context of AD.
      The purpose of this follow-up study was to assess the benefits of a brain
      selective 17beta-estradiol estrogen prodrug, 10beta,17beta-hydroxyestra-1,4-dien
      3-one (DHED), also in the male APPswe/PS1dE9 double-transgenic mouse model of the
      disease. After continuously exposing 6-month old animals to DHED for two months,
      their brains showed decreased amyloid precursor and amyloid-beta protein levels.
      The DHED-treated APPswe/PS1dE9 double transgenic subjects also exhibited enhanced
      performance in a cognitive task, while 17beta-estradiol treatment did not reach
      statistical significance. Taken together, data presented here suggest that DHED
      may also have therapeutic benefit in males and warrant further investigations to
      fully elucidate the potential of targeted estrogen therapy for a gender
      independent treatment of early-stage AD.

PMID- 29183690
TI  - Home-based intravenous analgesia with elastomeric pump as an outpatient procedure
      for pain control after anterior cruciate ligament repair.
AB  - OBJECTIVE: To follow up pain in the immediate postoperative period, using an
      elastomeric pump in anterior cruciate ligament surgery. MATERIAL AND METHODS: 309
      patients who had undergone anterior cruciate ligament repair with bone-tendon
      bone allograft. Pain control was assessed with a visual analogue scale (VAS)
      during the immediate postoperative period, in the postoperative care unit, in the
      recovery room, and after the first 24-48-72hours following home discharge. The
      need for rescue medication, adverse effects observed and emergency visits were
      also registered. RESULTS: 309 patients were assessed (264 males, 45 females),
      mean age 33 (range: 18 - 55). Postoperative pain was mild in 44.7% of patients,
      and 38.5% were pain-free. At discharge, 41.1% of patients reported mild pain and
      57% were pain-free. At home, mild to moderate levels of pain were maintained and
      over 97% of patients presented VAS values <= 3. Fewer than 3% had adverse
      effects, 8.7% had to use analgesic medication at some point. Pruritus occurred in
      less than 1% of patients receiving intravenous analgesia at home, and fewer than
      2% had device-related complications. DISCUSSION: There is no consensus regarding
      the postoperative management of anterior cruciate ligament lesions, although most
      surgeons use multimode anaesthesia and different combinations of analgesics to
      reduce postoperative pain. CONCLUSIONS: The use of an intravenous elastomeric
      pump as postoperative analgesia for anterior cruciate ligamentoplasty has yielded
      good results.

PMID- 29183692
TI  - Reply to "Hypoalbuminemia is a predictor of mortality and rebleeding in peptic
      ulcer bleeding under proton pump inhibitor use: Methodological issues".

PMID- 29183691
TI  - Regional differences of cFos immunoreactive cells in the preoptic areas in
      hypothalamus associated with heat and cold responses in mice.
AB  - cFos expression in the preoptic area (PO), which is thermoregulatory center
      increased by both heat and cold exposures; however, the regional difference is
      unknown yet. We aimed to determine if cFos expression in the PO was regionally
      different between heat and cold exposures. Mice were exposed to 27, 10, or 38
      degrees C for 90min, and body temperature (Tb) was measured. cFos-immunoreactive
      (cFos-IR) cells in the PO were counted by separating the PO into the ventral and
      dorsal parts in the rostral (bregma 0.38mm), central (-0.10mm), and caudal (
      0.46mm) planes. Tb at 10 degrees C remained unchanged; however, it increased at
      38 degrees C. Counts of cFos-IR cells in all areas were greater at 38 degrees C
      than at 27 degrees C. In the dorsal and ventral parts of the central and the
      dorsal part of caudal PO, counts of cFos-IR cells were greater at 10 degrees C
      than at 27 degrees C. In conclusion, the areas of increased cFos expression in
      the PO in the heat were different that in the cold in mice.

PMID- 29183693
TI  - Glutathione depletion: Starting point of brain metabolic stress,
      neuroinflammation and cognitive impairment in rats.
AB  - Glutathione provides protection from oxidative stress-induced damage through the
      reduction of reactive oxygen species for the maintenance of oxidant homeostasis.
      Our purpose was to test the effects of depleting tissue GSH by buthionine
      sulfoximine on brain oxidative metabolism and cognitive performance in rats.
      Glutathione depletion induced a compensatory response on antioxidant enzymes and
      increase of cell damage indicators in all the examined cerebral areas at 24h. The
      effect of GSH depletion on spatial memory recorded at 24h post-surgery showed
      significant differences between experimental groups for the escape latency to the
      platform and percentage of total swim distance spending in the target quadrant.
      The acquisition of a new spatial condition 24h after GSH depletion revealed
      differences between experimental groups for latencies, swim distance, swim
      distance in the target quadrant and percentage of total swim distance spending in
      the target quadrant. The ability of BSO treated group to maintain a restraining
      behavior was significantly smaller compared with control group. We founded
      significant correlation among variables of the behavioral studies and oxidative
      stress indicators. In conclusion, our model shows how increased ROS production by
      transitory glutathione depletion constitutes the primary cause to neuronal
      metabolic stress with alterations in synaptic signaling and cognitive deficits.

PMID- 29183694
TI  - Isolation of 2-deoxy-scyllo-inosose (DOI)-assimilating yeasts and cloning and
      characterization of the DOI reductase gene of Cryptococcus podzolicus ND1.
AB  - 2-Deoxy-scyllo-inosose (DOI) is the first intermediate in the 2-deoxystreptamine
      containing aminoglycoside antibiotic biosynthesis pathway and has a six-membered
      carbocycle structure. DOI is a valuable material because it is easily converted
      to aromatic compounds and carbasugar derivatives. In this study, we isolated
      yeast strains capable of assimilating DOI as a carbon source. One of the strains,
      Cryptococcus podzolicus ND1, mainly converted DOI to scyllo-quercitol and (-)
      vibo-quercitol, which is a valuable compound used as an antihypoglycemia agent
      and as a heat storage material. An NADH-dependent DOI reductase coding gene,
      DOIR, from C. podzolicus ND1 was cloned and successfully overexpressed in
      Escherichia coli. The purified protein catalyzed the irreversible reduction of
      DOI with NADH and converted DOI into (-)-vibo-quercitol. The enzyme had an
      optimal pH of 8.5 and optimal temperature of 35 degrees C, respectively. The kcat
      of this enzyme was 9.98 s-1, and the Km values for DOI and NADH were 4.38 and
      0.24 mM, respectively. The enzyme showed a strong preference for NADH and showed
      no activity with NADPH. Multiple-alignment analysis of DOI reductase revealed
      that it belongs to the GFO_IDH_MocA protein family and is an inositol
      dehydrogenase homolog in other fungi, such as Cryptococcus gattii, and bacteria,
      such as Bacillus subtilis. This is the first identification of a DOI-assimilating
      yeast and a gene involved in DOI metabolism in fungi.

PMID- 29183695
TI  - Discrimination of wine from grape cultivated in Japan, imported wine, and others
      by multi-elemental analysis.
AB  - Differences in mineral concentrations were examined among three types of wine in
      the Japanese market place: Japan wine, imported wine, and domestically produced
      wine mainly from foreign ingredients (DWF), where Japan wine has been recently
      defined by the National Tax Agency as domestically produced wine from grapes
      cultivated in Japan. The main objective of this study was to examine the
      possibility of controlling the authenticity of Japan wine. The concentrations of
      18 minerals (Li, B, Na, Mg, Si, P, S, K, Ca, Mn, Co, Ni, Ga, Rb, Sr, Mo, Ba, and
      Pb) in 214 wine samples were determined by inductively coupled-plasma mass
      spectrometry (ICP-MS) and ICP-atomic emission spectrometry (ICP-AES). In general,
      Japan wine had a higher concentration of potassium and lower concentrations of
      eight elements (Li, B, Na, Si, S, Co, Sr, and Pb) as compared with the other two
      groups of wine. Linear discriminant analysis (LDA) models based on concentrations
      of the 18 minerals facilitated the identification of three wine groups: Japan
      wine, imported wine, and DWF with a 91.1% classification score and 87.9%
      prediction score. In addition, an LDA model for discrimination of wine from four
      domestic geographic origins (Yamanashi, Nagano, Hokkaido, and Yamagata
      Prefectures) using 18 elements gave a classification score of 93.1% and a
      prediction score of 76.4%. In summary, we have shown that an LDA model based on
      mineral concentrations is useful for distinguishing Japan wine from other wine
      groups, and can contribute to classification of the four main domestic wine
      producing regions of Japan.

PMID- 29183696
TI  - Isolation of 5-hydroxymethylfurfural biotransforming bacteria to produce 2,5
      furan dicarboxylic acid in algal acid hydrolysate.
AB  - In dealing with lignocellulosic and algal biomass, thermal acid hydrolysis is an
      economical and efficient method. In this process, 5-hydroxy-methylfurfural (5
      HMF) is formed unavoidably, which inhibits downstream reducing sugar
      fermentation. Fortunately, 5-HMF can be biotransformed into 2,5-furan
      dicarboxylic acid (FDCA), the top 14 biomass platform molecules. Base on the
      connection between 5-HMF removal and FDCA production, microbes capable of
      biotransforming 5-HMF into FDCA are beneficial to raise biofuel yield and
      potential molecule production. In this research, pure strain Methylobacterium
      radiotolerans G-2 capable of transforming 5-HMF into FDCA was enriched and
      isolated from local campus soil, and its abilities of 5-HMF biotransformation and
      FDCA production were characterized. Strain M. radiotolerans G-2 could completely
      transform 1000 mg/L 5-HMF into FDCA with maximum concentration of 513.9 mg/L at
      an initial pH of 7 at 26 degrees C. Algal acid hydrolysate after two-fold
      dilution was suitable for strain M. radiotolerans G-2 to perform 5-HMF
      biotransformation, and 459.7 mg/L FDCA could be obtained. Interestingly, strain
      M. radiotolerans G-2 did not significantly consume reducing sugar and reducing
      sugar consuming efficiency was less than 16%.

PMID- 29183697
TI  - The potential impact on the biodegradation of organic pollutants from composting
      technology for soil remediation.
AB  - Large numbers of organic pollutants (OPs), such as polycyclic aromatic
      hydrocarbons, pesticides and petroleum, are discharged into soil, posing a huge
      threat to natural environment. Traditional chemical and physical remediation
      technologies are either incompetent or expensive, and may cause secondary
      pollution. The technology of soil composting or use of compost as soil amendment
      can utilize quantities of active microbes to degrade OPs with the help of
      available nutrients in the compost matrix. It is highly cost-effective for soil
      remediation. On the one hand, compost incorporated into contaminated soil is
      capable of increasing the organic matter content, which improves the soil
      environment and stimulates the metabolically activity of microbial community. On
      the other hand, the organic matter in composts would increase the adsorption of
      OPs and affect their bioavailability, leading to decreased fraction available for
      microorganism-mediated degradation. Some advanced instrumental analytical
      approaches developed in recent years may be adopted to expound this process.
      Therefore, the study on bioavailability of OPs in soil is extremely important for
      the application of composting technology. This work will discuss the changes of
      physical and chemical properties of contaminated soils and the bioavailability of
      OPs by the adsorption of composting matrix. The characteristics of OPs, types and
      compositions of compost amendments, soil/compost ratio and compost distribution
      influence the bioavailability of OPs. In addition, the impact of composting
      factors (composting temperature, co-substrates and exogenous microorganisms) on
      the removal and bioavailability of OPs is also studied.

PMID- 29183698
TI  - Titanium and polyether ether ketone (PEEK) patient-specific sub-periosteal
      implants: two novel approaches for rehabilitation of the severely atrophic
      anterior maxillary ridge.
AB  - The aim of this study was to assess two new protocols for single-stage
      rehabilitation of the severely atrophic maxillary ridge using customized porous
      titanium or polyether ether ketone (PEEK) sub-periosteal implants. Ten patients
      with a severely atrophic anterior maxillary alveolar ridge were divided randomly
      into two groups (five patients in each) to receive customized sub-periosteal
      implants fabricated via CAD/CAM technology: group 1, porous titanium implants;
      group 2, PEEK implants. Prosthetic loading with fixed acrylic bridges was
      performed 1 month postoperative. The implants were followed-up for 12 months and
      evaluated for the presence of any sign of radiographic bone resorption, mobility,
      infection, prosthetic fracture, or implant exposure. The immediate postoperative
      period was uneventful except for one case complicated by wound dehiscence in
      group 1. At 12 months, all implants were functionally stable and the patients
      were comfortable with the prostheses. No signs of radiographic bone resorption,
      mobility, infection, or prosthetic fracture were observed. Within the limitations
      of this study, the application of customized porous titanium and PEEK sub
      periosteal implants produced through CAD/CAM technology appears to be an
      acceptable method for single-stage prosthetic rehabilitation of the severely
      atrophic edentulous anterior maxilla. This study was awarded the best case study
      at the academy of osseintegration annual meeting 2017, Orlando, Florida.

PMID- 29183699
TI  - Three-dimensional changes to the upper airway after maxillomandibular advancement
      with counterclockwise rotation: a systematic review and meta-analysis.
AB  - The aim of this study was to evaluate the effect of counterclockwise (CCW)
      rotation and maxillomandibular advancement (MMA) on the upper airway space using
      three-dimensional images. An electronic search was performed in the PubMed,
      Cochrane Library, Scopus, Virtual Health Library, Web of Science, and OpenGrey
      databases (end date July 2016); a hand-search of primary study reference lists
      was also conducted. The inclusion criteria encompassed computed tomography
      evaluations of the upper airway spaces of adult patients undergoing orthognathic
      surgery with CCW rotation and MMA. The articles were evaluated for risk of bias
      with a tool for before-and-after studies. A meta-analysis was performed with the
      mean differences using a random-effects model. Heterogeneity was assessed with
      the Q-test and the I2 index. The meta-analysis revealed significant (P<0.001)
      increases in both the total airway volume (effect size of 6832mm3 and confidence
      interval of 5554-8109mm3) and the minimum axial area (effect size of 92mm2 and
      confidence interval of 70-113mm2). The heterogeneity was low in both comparisons
      (I2=38% and 7%, respectively). The technique of mandibular advancement with CCW
      rotation produced significant increases in the volumes and areas of the upper
      airway spaces.

PMID- 29183700
TI  - Attachment and eating: A meta-analytic review of the relevance of attachment for
      unhealthy and healthy eating behaviors in the general population.
AB  - Attachment relationships play an important role in people's wellbeing and
      affliction with physical and mental illnesses, including eating disorders. Seven
      reviews from the clinical field have consistently shown that higher attachment
      insecurity-failure to form trusting and reliable relationships with others
      systematically characterized individuals with eating disorders. Nevertheless, to
      date, it is unclear whether (and if so how) these findings apply to the
      population at large. Consequently, the objective of the present meta-analysis is
      to quantify the relationship between attachment and unhealthy and healthy eating
      in the general population. Data from 70 studies and 19,470 participants were
      converted into r effect sizes and analysed. Results showed that higher attachment
      insecurity (r = 0.266), anxiety (r = 0.271), avoidance (r = 0.119), and
      fearfulness (r = 0.184) was significantly associated with more unhealthy eating
      behaviors, ps = 0.000; conversely, higher attachment security correlated with
      lower unhealthy eating behaviors (r = -0.184, p = 0.000). This relationship did
      not vary across type of unhealthy eating behavior (i.e., binge eating, bulimic
      symptoms, dieting, emotional eating, and unhealthy food consumption). The little
      exploratory evidence concerning healthy eating and attachment was inconclusive
      with one exception-healthy eating was associated with lower attachment avoidance
      (r = -0.211, p = 0.000). Our results extend previous meta-analytic findings to
      show that lack of trusting and reliable relationships does not only set apart
      eating disordered individuals from controls, but also characterizes unhealthy
      eating behaviors in the general population. More evidence is needed to determine
      how attachment and healthy eating are linked and assess potential mechanisms
      influencing the attachment-eating relationship.

PMID- 29183702
TI  - Minimally invasive hepatectomy conversions: an analysis of risk factors and
      outcomes.
AB  - BACKGROUND: Surgical approach may influence morbidity following hepatectomy. This
      study sought to compare outcomes in minimally invasive surgery (MIS), conversion
      from MIS to open, and planned open hepatectomy patients and analyze factors
      leading to conversion. METHODS: The 2014 National Surgical Quality Improvement
      Program dataset was queried for patients undergoing hepatectomy. Patients were
      divided into three cohorts: MIS, open, or conversion. Propensity matching was
      performed to compare MIS vs. conversion (3:1) and open vs. conversion (8:1). The
      logistic regression model was used to identify odds ratios for conversion.
      RESULTS: Patients undergoing conversion had a higher transfusion rate (26% vs.
      9%, p < 0.001), longer length of stay (5 vs. 3 days, p < 0.001), and higher
      morbidity (38% vs. 18%, p < 0.001) than MIS patients. Patients who underwent
      conversion had similar short-term outcomes to those who had planned open
      procedures. Independent predictors of conversion included hypertension (OR 1.91;
      95% CI 1.12-3.26) and right lobectomy (OR 20.23; 95% CI 3.74-109.35). CONCLUSION:
      Patients with hypertension and those undergoing right lobectomy had a higher risk
      of conversion to open procedure. Conversion resulted in higher morbidity and
      longer length of stay compared to MIS patients, but outcomes were similar to
      planned open procedures.

PMID- 29183701
TI  - Effect of snack-food proximity on intake in general population samples with
      higher and lower cognitive resource.
AB  - OBJECTIVE: Placing snack-food further away from people consistently decreases its
      consumption ("proximity effect"). However, given diet-related health
      inequalities, it is important to know whether interventions that alter food
      proximity have potential to change behaviour regardless of cognitive resource
      (capacity for self-control). This is often lower in those in lower socio-economic
      positions, who also tend to have less healthy diet-related behaviours. Study 1
      aims to replicate the proximity effect in a general population sample and
      estimate whether trait-level cognitive resource moderates the effect. In a
      stronger test, Study 2 investigates whether the effect is similar regardless of
      manipulated state-level cognitive resource. METHOD: Participants were recruited
      into two laboratory studies (Study 1: n = 159; Study 2: n = 246). A bowl of an
      unhealthy snack was positioned near (20 cm) or far (70 cm) from the participant,
      as randomised. In Study 2, participants were further randomised to a cognitive
      load intervention. The pre-specified primary outcome was the proportion of
      participants taking any of the snack. RESULTS: Significantly fewer participants
      took the snack when far compared with near in Study 2 (57.7% vs 70.7%, beta = 
      1.63, p = 0.020), but not in Study 1 (53.8% vs 63.3%, X2 = 1.12, p = 0.289).
      Removing participants who moved the bowl (i.e. who did not adhere to protocol),
      increased the effect-sizes: Study 1: 39.3% vs 63.9%, X2 = 6.43, p = 0.011; Study
      2: 56.0% vs 73.9%, beta = -2.46, p = 0.003. Effects were not moderated by
      cognitive resource. CONCLUSIONS: These studies provide the most robust evidence
      to date that placing food further away reduces likelihood of consumption in
      general population samples, an effect unlikely to be moderated by cognitive
      resource. This indicates potential for interventions altering food proximity to
      contribute to addressing health inequalities, but requires testing in real-world
      settings. TRIAL REGISTRATION: Both studies were registered with ISRCTN (Study 1
      reference no.: ISRCTN46995850, Study 2 reference no.: ISRCTN14239872).

PMID- 29183703
TI  - A comparison of outcomes between open, laparoscopic and robotic
      pancreaticoduodenectomy.
AB  - BACKGROUND: The advantages and comparison of minimally invasive techniques for
      pancreaticoduodenectomies have not been fully explored using large national
      multicenter data. STUDY DESIGN: A retrospective review of NSQIP targeted data
      from 2014 to 2015 was performed. Demographics and outcomes were compared between
      open (OPD), laparoscopic (LPD) and robotic pancreaticoduodenectomies (RPD).
      RESULTS: Of 6827 pancreaticoduodenectomies, 6336 (92.8%) were OPD, 280 (4.1%)
      were LPD, and 211 (3.1%) were RPD. Compared to OPD, LPD required more post
      operative drainage procedures (18.4% vs 13.2%, p = 0.013), had less SSI (3.2% vs
      9%, p = 0.001), and had fewer discharges to a new facility (8.1% vs 13%, p =
      0.018). Compared to OPD, RPD had less perioperative transfusions (14.2% vs 20.5%,
      p = 0.026) and more readmissions (23.2% vs 16.7%, p = 0.013). After controlling
      for differences, LPD was independently associated with decreased 30-day morbidity
      compared to OPD (OR 0.75, 95% CI 0.56-0.99). There was no difference in 30-day
      mortality. CONCLUSIONS: This is the first study to compare the outcomes of
      laparoscopic and robotic pancreaticoduodenectomies to open using the NSQIP
      database. After controlling for differences between groups, LPD is independently
      associated with less morbidity. In experienced hands, it appears safe and
      valuable to pursue refinement of minimally invasive techniques for
      pancreaticoduodenectomies.

PMID- 29183704
TI  - Reperfusion of myocardial infarction in India: Notions for Mexico.
AB  - In India and Mexico, cardiovascular diseases are the first cause of death and
      potential years of life lost. Close similarities exist between these two
      countries when facing the difficulties to establish a universal reperfusion
      program for ST elevation myocardial infarction (STEMI). This paper describes the
      situation of STEMI treatment in both countries, and examines the lessons that
      Mexico's health care system could adopt from the recent advances accomplished by
      the STEMI initiative in India.

PMID- 29183705
TI  - [Kounis syndrome].

PMID- 29183706
TI  - Differential behavioral phenotypes of dopamine D1 receptor knockdown mice at the
      embryonic, postnatal, and adult stages.
AB  - Dopamine is widely involved in behaviors related to motor activity, cognition,
      motivation, and reward. Dopamine signal is transduced through the dopamine
      receptor gene family. The dopamine D1 receptor (D1R) is highly expressed in the
      striatum, and is responsible for regulating the motor function. Recently, we have
      reported that the knockdown (KD) mice in which D1R was conditionally eliminated
      at adult stage, displayed a hypoactivity in the home cage than wild type mice;
      however, conventional D1R knockout (KO) mice show hyperactive phenotypes. In
      order to assess whether the difference in the time of eliminating D1R expression
      affects the behavioral phenotypes, we generated D1R KD mice at the postnatal and
      adult stages, and compared their motor function with D1R KO mice. Consequently,
      D1R KD at postnatal and adult stages resulted in severe locomotive defects
      compared with D1R KO mice. These results suggested that D1R has versatile
      functions, and the knockdown timing greatly influences the normal motor activity
      in the adolescent to adult stages.

PMID- 29183709
TI  - Unappreciated diversity within the pool of CD1d-restricted T cells.
AB  - Studies of lipid reactive CD1d-restricted T cells have focussed on alpha
      galactosylceramide reactive semi-invariant Type I NKT cells, which influence a
      broad range of immune responses. Much less is known about other CD1d-restricted T
      cells with respect to TCR diversity, function, the types of antigens they
      recognize and how they specifically recognize antigens presented by CD1d. In this
      review, we reflect on recent literature that highlights unexpected complexity
      within the pool of CD1d-restricted T cells and emphasize how TCR diversity
      greatly broadens the scope of antigen recognition.

PMID- 29183707
TI  - Visual outcomes and management after corneal refractive surgery: A review.
AB  - Corneal refractive surgery procedures are widely performed to permanently correct
      refractive errors. Overall, refractive surgeries are safe, predictable and
      present high rates of satisfaction. Nevertheless, the induced epithelial, stromal
      and nerve damage alters corneal integrity and function, triggering a regenerative
      response. Complications that arise from corneal wound healing process might
      directly impact on visual outcomes of keratorefractive procedures. Most of these
      complications can be prevented or effectively treated with minimal consequences
      and minor impact on optical quality. Nevertheless, it is crucial to accurately
      and timely identify these corneal regeneration-related complications for
      successful counseling and management. Optometrists, as primary eye care
      providers, play an essential role in detecting anatomic and functional
      alterations in vision. It is therefore of great interest for optometrists to be
      familiar with the principal postoperative complications derived from alterations
      in regenerative process after corneal laser refractive surgeries. This review
      aims to provide a basis for optometrists to better understand, identify and
      manage the main wound healing-related complications after refractive surgery.

PMID- 29183710
TI  - Osteoarthritis in Spain: A nationwide survey of medical specialists.
AB  - OBJECTIVE: To determine the reality of the resources and care needs in Spain for
      the management of patients with osteoarthritis. MATERIALS AND METHOD: An online
      survey. RESULTS: Description of 190 responses to a structured questionnaire (141
      orthopedic surgeons and 49 rheumatologists). CONCLUSIONS: Osteoarthritis has yet
      to receive appropriate medical attention and a patient management model.

PMID- 29183708
TI  - Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA
      binding proteins.
AB  - Alterations in lipoprotein metabolism enhance the risk of cardiometabolic
      disorders including type-2 diabetes and atherosclerosis, the leading cause of
      death in Western societies. While the transcriptional regulation of lipid
      metabolism has been well characterized, recent studies have uncovered the
      importance of microRNAs (miRNAs), long-non-coding RNAs (lncRNAs) and RNA binding
      proteins (RBP) in regulating the expression of lipid-related genes at the
      posttranscriptional level. Work from several groups has identified a number of
      miRNAs, including miR-33, miR-122 and miR-148a, that play a prominent role in
      controlling cholesterol homeostasis and lipoprotein metabolism. Importantly,
      dysregulation of miRNA expression has been associated with dyslipidemia,
      suggesting that manipulating the expression of these miRNAs could be a useful
      therapeutic approach to ameliorate cardiovascular disease (CVD). The role of
      lncRNAs in regulating lipid metabolism has recently emerged and several groups
      have demonstrated their regulation of lipoprotein metabolism. However, given the
      high abundance of lncRNAs and the poor-genetic conservation between species, much
      work will be needed to elucidate the specific role of lncRNAs in controlling
      lipoprotein metabolism. In this review article, we summarize recent findings in
      the field and highlight the specific contribution of lncRNAs and RBPs in
      regulating lipid metabolism.

PMID- 29183711
TI  - Mixed crystal arthropathy of the wrist: The contribution of imaging in the
      diagnostic approach.

PMID- 29183712
TI  - Correlation between the sudden jump-like increases of the atrio-Hisian interval
      induced during burst atrial pacing and during programmed atrial stimulation in
      patients with atrioventricular nodal reentrant tachycardia.
AB  - PURPOSE: To study the correlation between the sudden prolongations of the atrio
      Hisian (AH) interval with >=50 ms during burst and programmed atrial stimulation,
      and to define whether the AH jump during burst atrial pacing is a reliable
      diagnostic criterion for dual AV nodal physiology. METHODS: Retrospective data on
      304 patients with preliminary ECG diagnosis of AV nodal reentrant tachycardia
      (AVNRT), confirmed during electrophysiological study, was analyzed for the
      presence of AH jump during burst and programmed atrial stimulation, and for
      correlation between the pacing modes for inducing the jump. Wilcoxon signed-ranks
      test and Spearman's bivariate correlation coefficient were applied, significant
      was P-value <0.05. RESULTS: The population was aged 48.5 +/- 15.7 (12-85) years;
      males were 38.5%. AH jump occurred during burst atrial pacing in 81% of the
      patients, and during programmed stimulation - in 78%, P = 0.366. In 63.2% AH jump
      was induced by both pacing modes; in 17.8% - only by burst pacing; in 14.8% -
      only by programmed pacing; in 4.2% there was no inducible jump. There was
      negative correlation between both pacing modes, rho = -0.204, R<0.001.
      CONCLUSION: Burst and programmed atrial stimulation separately prove the presence
      of dual AV nodal physiology in 81 and 78% of the patients with AVNRT,
      respectively. There is negative correlation between the two pacing modes,
      allowing the combination of the two methods to prove diagnostic in 95.8% of the
      patients.

PMID- 29183713
TI  - Right bundle branch block pattern after uncomplicated right ventricular outflow
      tract pacing in a patient with a left sided superior vena cava and corrected
      tetralogy of Fallot.
AB  - Usually an electrocardiogram after right ventricular (RV) pacing should yield
      left bundle branch block (LBBB) pattern. However, the presence of right bundle
      branch block (RBBB) pattern after pacemaker implantation should alert the
      physician to a malposition of lead. We report a case of 18-year-old female who
      underwent dual chamber pacemaker implantation and had RBBB pattern post
      implantation. Detailed evaluation revealed an uncomplicated right ventricular
      outflow tract pacing. The possible causes of this abnormal pattern after an
      uncomplicated RV pacing are also reviewed.

PMID- 29183714
TI  - Interesting response of narrow QRS tachycardia to premature atrial complex. What
      is the mechanism?

PMID- 29183715
TI  - Novel mutations and a severe neurological phenotype in Sjogren-Larsson syndrome
      patients from Iran.
AB  - Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive disorder
      characterized by ichthyosis, spasticity and intellectual disability. The disease
      is caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde
      dehydrogenase. We describe 7 Iranian SLS patients from 5 unrelated consanguineous
      families. Sequencing of ALDH3A2 identified 4 novel mutations, including a 26-bp
      deletion (c.25_50del), small in-frame deletion (c.370_372del; p.G124del), a
      termination (p.Q35Ter) and a missense mutation (p.Lys211Glu). Bacterial
      expression of the p.Lys211Glu and p.G124del mutations showed little or no
      detectable enzyme activity. Three of the patients exhibited an unusual neuro
      regressive clinical course associated with seizures, which may reflect the
      presence of unidentified genetic or environmental modifiers in this
      consanguineous population. This cohort represents the largest group of Iranian
      patients with molecularly confirmed SLS and expands the mutational and clinical
      spectrum of this disease.

PMID- 29183716
TI  - The Effect of Total Size of Lesions in Multifocal/Multicentric Breast Cancer on
      Survival.
AB  - BACKGROUND: In this study, we aimed to assess the prognostic performance of
      determining the T stage according to the total size of lesions compared with the
      size of the largest lesion in the breast in patients with multifocal/multicentric
      (MF/MC) breast cancer. PATIENTS AND METHODS: The charts of the patients with
      MF/MC breast cancer who were diagnosed between 2003 and 2014 were reviewed. The T
      stage of MF/MC tumors was determined according to the largest lesion size (Tmax)
      as well as the sum of the longest diameters of the lesions (Tsum) in the breast.
      RESULTS: Multifocal/multicentric tumors were identified in 323 of 3890 patients
      (8.3%) with breast cancer. Ten-year rates of overall survival (OS; 75% and 74%; P
      = .965) and disease-free survival (DFS; 66% and 61%; P = .817) were similar in
      patients with unifocal and MF/MC tumors, respectively. When the T stage was
      determined by summing the sizes of the lesions, the T stage of 67 (20.7%) and 63
      (19.5%) patients advanced from T1 to T2 and from T2 to T3, respectively. Thus,
      the T stage increased in 130 patients (40.2%) according to American Joint
      Committee on Cancer. Discriminatory ability of Tsum was better than Tmax in terms
      of OS and DFS, as shown with higher Royston D and Harrel C statistics and
      Schemper V values. CONCLUSION: The new T classification proposed in this report
      stands out as a better predictive classification particularly in patients with
      low disease burden.

PMID- 29183718
TI  - Identification and characterization of PP2C phosphatase SjPtc1 in Schistosoma
      japonicum.
AB  - Protein phosphorylation, regulated by protein kinases and protein phosphatases,
      is crucial for protein structure and function in eukaryotic organisms. Type 2C
      protein phosphatase (PP2C) belongs to the serine/threonine phosphatase family and
      its activities require the presence of a divalent magnesium or manganese ion. In
      the present study, a potential PP2C phosphatase (SjPtc1) was identified in
      Schistosoma japonicum. The SjPTC1 gene was found to be highly expressed in adult
      worms. A recombinant SjPtc1 protein showed typical PP2C phosphatase activity.
      Heterologous SjPTC1 expression reversed the sensitivity of yeast ptc1 null
      mutants toward H2O2, ZnCl2, cisplatin, and rapamycin. Collectively, the results
      suggest that SjPtc1 may take part in the regulation of cellular responses to
      oxidative stress, DNA damage stress, and the TOR (target of rapamycin) signaling
      pathway.

PMID- 29183717
TI  - Using Wolbachia for Dengue Control: Insights from Modelling.
AB  - Dengue is the most common arboviral infection of humans, responsible for a
      substantial disease burden across the tropics. Traditional insecticide-based
      vector-control programmes have limited effectiveness, and the one licensed
      vaccine has a complex and imperfect efficacy profile. Strains of the bacterium
      Wolbachia, deliberately introduced into Aedes aegyptimosquitoes, have been shown
      to be able to spread to high frequencies in mosquito populations in release
      trials, and mosquitoes infected with these strains show markedly reduced vector
      competence. Thus, Wolbachia represents an exciting potential new form of
      biocontrol for arboviral diseases, including dengue. Here, we review how
      mathematical models give insight into the dynamics of the spread of Wolbachia,
      the potential impact of Wolbachia on dengue transmission, and we discuss the
      remaining challenges in evaluation and development.

PMID- 29183720
TI  - Contemporary Applications of Fecal Microbiota Transplantation to Treat Intestinal
      Diseases in Humans.
AB  - The intestinal microbiota comprise an important organ that plays a vital role in
      host digestion, development, energy maintenance, hemostasis, and immunity.
      Disruption of the gut microbial community due to diet, lifestyle, or antibiotic
      exposure increases susceptibility to chronic infection and disease. Fecal
      microbiota transplantation (FMT) involves the transfer of gut microbiota from a
      healthy donor to a patient in order to restore normal diversity and function of
      the microbial community. This method has become a well established alternative
      therapy for the treatment of recurrent Clostridium difficile infection. Recent
      clinical trials and studies in animal models suggest promise for this method to
      treat inflammatory bowel diseases, as well as metabolic syndrome. In addition,
      due to signaling interactions between the gut microbiota and brain, FMT has been
      suggested as a potential treatment for some psychological disorders, including
      autism spectrum disorder. Importantly, advances in next-generation sequencing and
      multi-omics approaches are increasingly improving our understanding of the
      mechanisms by which FMT results in cure of these various conditions. In this
      review, we summarize the current applications of FMT and highlight potential
      future uses and current challenges in understanding and optimizing FMT
      procedures.

PMID- 29183721
TI  - Role of Chromatin assembly factor 1 in DNA replication of Plasmodium falciparum.
AB  - Nucleosome assembly in P. falciparum could be the key process in maintaining its
      genomic integrity as DNA replicates more than once per cell cycle during several
      stages of its life cycle. Here, we report the functional characterization of P.
      falciparum chromatin assembly factor 1 (CAF1), which interacts with several
      proteins namely PfCAF2, Histones, PfHP1 and others. Consistent with the above
      findings, we demonstrate the presence of PfCAF1 at the telomeric repeat regions,
      central and subtelomeric var genes of multiple var gene family along with PfHP1.
      Further, we report the upregulation of PfCAF1 after treatment with genotoxic
      agents like MMS and HU. Together, these findings establish role of PfCAF1 in
      heterochromatin maintenance and as histone chaperone in nucleosome assembly and
      DNA damage repair.

PMID- 29183719
TI  - The diverse functions of the hepatitis B core/capsid protein (HBc) in the viral
      life cycle: Implications for the development of HBc-targeting antivirals.
AB  - Virally encoded proteins have evolved to perform multiple functions, and the core
      protein (HBc) of the hepatitis B virus (HBV) is a perfect example. While HBc is
      the structural component of the viral nucleocapsid, additional novel functions
      for the nucleus-localized HBc have recently been described. These results extend
      for HBc, beyond its structural role, a regulatory function in the viral life
      cycle and potentially a role in pathogenesis. In this article, we review the
      diverse roles of HBc in HBV replication and pathogenesis, emphasizing how the
      unique structure of this protein is key to its various functions. We focus in
      particular on recent advances in understanding the significance of HBc
      phosphorylations, its interaction with host proteins and the role of HBc in
      regulating the transcription of host genes. We also briefly allude to the
      emerging niche for new direct-acting antivirals targeting HBc, known as Core
      (protein) Allosteric Modulators (CAMs).

PMID- 29183722
TI  - Kinetic regime of aggregation of UV-irradiated glyceraldehyde-3-phosphate
      dehydrogenase from rabbit skeletal muscle.
AB  - The study of the kinetics of aggregation of UV-irradiated proteins has attracted
      considerable interest, since test systems based on aggregation of proteins
      denatured by UV radiation can be used for screening of the natural and artificial
      agents possessing chaperone-like activity (anti-aggregation activity). To provide
      the proper interpretation of the effects caused by the agents under study, the
      kinetic mechanism of the aggregation process should be established. In the
      present work the kinetic data on aggregation of UV-irradiated glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) from rabbit skeletal muscle at 37  degrees C
      (O.I. Maloletkina et al. Biophys. Chem. 163-164 (2012) 11-20) have been analyzed.
      It has been shown that the stage of aggregate growth follows the first-order
      kinetics and the experimentally measured rate constant of the first order
      corresponds to heat-induced structural reorganization of UV-irradiated GAPDH
      containing concealed damage.

PMID- 29183723
TI  - SREBP1-driven lipid desaturation supports clear cell renal cell carcinoma growth
      through regulation of NF-kappaB signaling.
AB  - Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancers,
      is an incurable and lethal disease. Although great progresses have been made in
      understanding the mechanism of ccRCC, metabolic reprogramming in ccRCC remains
      largely unclear. Here, we showed that lipid desatutation might be a metabolic
      hallmark of ccRCC. We demonstrated sterol regulatory element-binding protein 1
      (SREBP1) is overexpressed in ccRCC cell lines and positively correlated with NF
      kappaB activation. Further, SREBP1 is required for lipid desaturation and cell
      growth in ccRCC. Mechanistically, we demonstrated that SREBP1-driven lipid
      desaturation promotes NF-kappaB activation. Our finding reveals a crucial roles
      for SREBP1 in lipid desaturation of ccRCC through regulation of NF-kappaB
      signaling, which provides not only new insights in regulatory mode of NF-kappaB
      signaling but also a novel target for potential metabolic therapies.

PMID- 29183724
TI  - CD40L and TNF both activate the classical NF-kappaB pathway, which is not
      required for the CD40L induced alternative pathway in endothelial cells.
AB  - CD40L and TNF signal through engagement of their respective receptors, which are
      both members of the TNF receptor family. They use partially common signaling
      molecules leading, among others, to activation of the NF-kappaB pathway. However,
      whereas TNF activates the classical, CD40L has been reported to activate the
      alternative NF-kappaB pathway, leading to the anticipation that differences in
      the pattern of inflammatory gene expression would occur. Here, we have compared
      the gene expression repertoire of CD40L (CD154) and TNF stimulated HUVEC and
      report that unexpectedly, apart from a stronger response to TNF, no major
      qualitative differences could be observed. This applies for the period of up to 6
      h, a time where the alternative pathway has already been activated. Analysis of
      the early events after receptor engagement revealed that both TNF and CD40L
      activate the classical NF-kappaB pathway, and confirm activation of the
      alternative by the latter. Furthermore, using genetic and pharmacological
      inhibition of the classical pathway we show that activation of the alternative
      occurs independently of the former. This reveals novel insights into NF-kappaB
      signaling by CD40L and TNF in endothelial cells.

PMID- 29183725
TI  - Involuntary swimming exercise in pregnant rats disturbs ERK1/2 signaling in
      embryonic neurons through increased cortisol in the amniotic fluid.
AB  - Harmful maternal behaviors, such as drinking and smoking, negatively affect
      embryonic development. In contrast, regular maternal exercise is believed to be
      beneficial to the fetus. Although it is not surprising that voluntary physical
      activities are advantageous to fetal development, it remains unclear whether
      involuntary maternal exercise has similar effects. The constituents of the
      amniotic fluid (AF) inevitably reflect the maternal plasma. Therefore, it is
      speculated that exercise-induced changes in maternal plasma can influence fetal
      development through changes in AF composition. Therefore, we investigated the
      effect of AF on fetal neurodevelopment and changes in AF composition after
      involuntary swimming exercise (SE) in an animal model. We found that there was a
      severe reduction in the number of embryos implanted in the uterus of SE rats.
      Surprisingly, cortisol level (an inducible stress hormone) was significantly
      increased in AF from SE rats. In contrast, the growth factors NGF and VEGF were
      reduced in the AF from SE rats. In the cultured embryonic cortical neurons, the
      treatment of control (CTL) rat-derived AF significantly increased the
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated
      signaling that is essential for fetal neurodevelopment. However, the AF extracted
      from SE rats reversely suppressed the phosphorylation of ERK1/2-mediated
      signaling in cortical neurons compared to that in CTL rats. Indeed, the co
      treatment with control AF and dexamethasone, a synthetic glucocorticoid,
      inhibited the phosphorylation of ERK1/2 in a dose-dependent manner. This finding
      suggests that the inhibition of ERK1/2 can be attributed to increased cortisol
      level in AF resulting from involuntary exercise. Therefore, involuntary maternal
      swimming increases cortisol level in AF, which ultimately hinders the ERK1/2
      signaling pathway in embryonic neurons. These findings also suggest that
      involuntary maternal exercise can have undesirable effects on fetal
      neurodevelopment, which is potentially mediated by elevated AF cortisol level.

PMID- 29183726
TI  - GSDME mediates caspase-3-dependent pyroptosis in gastric cancer.
AB  - Gastric cancer is a malignancy that starts from the cells in the stomach with
      relatively low overall survival rate. Chemotherapy following resection surgery
      has been recommended as a curative strategy for gastric cancer. However, the
      mechanism of the chemotherapy drugs on gastric cancer is not completely
      understood. Pyroptosis is a form of programmed cell death and plays critical role
      in immunity. The role of pyroptosis on cancer cells is less known. In this study,
      we treated SGC-7901 and MKN-45 with 5-FU and found that the cell viability was
      significantly decreased. The release of LDH and the percentage of PI and APC
      Annexin-V double positive cells after 5-FU treatment were elevated compared to
      control group. Moreover, there were large bubbles blowing from the membrane of 5
      FU-treated cells and the cleavage of GSDME but not GSDMD, which were blocked by
      the silence or specific inhibitor of caspase-3. Additionally, GSDME knockout by
      CRISPR-Cas9 switched 5-FU induced pyroptosis into apoptosis in SGC-7901. In
      conclusion, our findings firstly revealed that GSDME switches chemotherapy drug
      induced caspase-3 dependent apoptosis into pyroptosis in gastric cancer cells.

PMID- 29183727
TI  - Resveratrol strongly enhances the retinoic acid-induced superoxide generating
      activity via up-regulation of gp91-phox gene expression in U937 cells.
AB  - The membrane bound cytochrome b558 composed of gp91-phox and p22-phox proteins,
      and cytosolic proteins p40-, p47-and p67-phox are important components of
      superoxide (O2-)-generating system in phagocytes. Here, we describe that
      resveratrol, a pleiotropic phytochemical belonging to the stilbenoids,
      dramatically activates the O2--generating system during retinoic acid (RA)
      induced differentiation of human monoblastic leukemia U937 cells to macrophage
      like cells. When U937 cells were cultured in the presence of RA and resveratrol,
      the O2--generating activity increased more than 5-fold compared with that in the
      absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA
      and resveratrol strongly enhanced transcription of the gp91-phox compared with
      those of the RA-treatment only. On the other hand, immunoblot analysis revealed
      that co-treatment with RA and resveratrol caused remarkable accumulation of
      protein levels of gp91-phox (to 4-fold), p22-phox (to 5-fold) and p47-phox (to 4
      fold) compared with those of the RA-treatment alone. In addition, ChIP assay
      suggested that resveratrol participates in enhancing the gene expression of gp91
      phox via promoting acetylation of Lys-9 residues and Lys-14 residues of histone
      H3 within chromatin around the promoter regions of the gene. These results
      suggested that resveratrol strongly enhances the RA-induced O2--generating
      activity via up-regulation of gp91-phox gene expression in U937 cells.

PMID- 29183728
TI  - Lycium barbarum polysaccharide protects against oxygen glucose
      deprivation/reoxygenation-induced apoptosis and autophagic cell death via the
      PI3K/Akt/mTOR signaling pathway in primary cultured hippocampal neurons.
AB  - Lycium barbarum polysaccharide (LBP) is the main active ingredient of Lycium
      barbarum, which exhibits several beneficial effects, including neuroprotection,
      anti-aging and anti-oxidation. However, the mechanism by which LBP protects
      against cerebral ischemia/reperfusion-induced injury remains obscure. In this
      study, we found that LBP pretreatment greatly attenuated oxygen glucose
      deprivation/reperfusion (OGD/R) injury in primary cultured hippocampal neurons.
      LBP also suppressed OGD/R-induced lactate dehydrogenase (LDH) leakage, and
      ameliorated oxidative stress. In addition, LBP significantly reduced OGD/R
      induced apoptosis and autophagic cell death. LBP caused the down-regulation of
      cleaved Caspase-3/Caspase-3, LC3II/LC3I and Beclin 1, as well as up-regulation of
      Bcl-2/Bax and p62. Furthermore, mechanistic studies indicated that LBP
      pretreatment increased p-Akt and p-mTOR levels after OGD/R. In summary, our
      results indicated that LBP protects against OGD/R-induced neuronal injury in
      primary hippocampal neurons by activating the PI3K/Akt/mTOR signaling pathway.

PMID- 29183729
TI  - miR-596 Modulates Melanoma Growth by Regulating Cell Survival and Death.
AB  - Tumors grow because cancer cells lack the ability to balance cell survival and
      death signaling pathways. miR-596, a microRNA located at the 8p23.3 locus, has
      been shown by the TCGA-Assembler to be deleted in a significant number of
      melanoma samples. Here, we also validated the low levels of miR-596 in melanoma
      compared to tissue nevi, and Kaplan-Meier curve analysis revealed that low miR
      596 expression was associated with worse overall survival. Moreover, we showed
      that miR-596 overexpression effectively inhibited MAPK/ERK signaling, cell
      proliferation, migration, and invasion and increased the cell apoptosis of
      melanoma cells. In addition, we found that miR-596 directly targets MEK1 and two
      apoptotic proteins, MCL1, and BCL2L1, in melanoma cells. Our findings indicated
      that miR-596 is an important miRNA that both negatively regulates the MAPK/ERK
      signaling pathway by targeting MEK1 and modulates the apoptosis pathway by
      targeting MCL1 and BCL2L1, suggesting that miR-596 could be a therapeutic
      candidate for treating melanoma, and a prognostic factor for melanoma patients.

PMID- 29183730
TI  - Aging-Associated Decline of Epidermal PSMD8 Contributes to Impaired Skin
      Function.

PMID- 29183733
TI  - Measles and rubella eradication.
AB  - This article discusses concepts of eradication, some issues relating to vertical
      and horizontal public health programs, some current issues relating to measles
      and rubella, and what we need to do about them. It concludes that measles and
      rubella/CRS can and should be eradicated. A target date should be established in
      2020 (or before). Eradication can only be accomplished in the context of
      strengthening ongoing immunization services and strengthening surveillance so it
      can guide activities. Additional resources will be required to achieve the goal.

PMID- 29183731
TI  - Intentional and Unintentional Medication Non-Adherence in Psoriasis: The Role of
      Patients' Medication Beliefs and Habit Strength.
AB  - Medication non-adherence is a missed opportunity for therapeutic benefit. We
      assessed "real-world" levels of self-reported non-adherence to conventional and
      biologic systemic therapies used for psoriasis and evaluated psychological and
      biomedical factors associated with non-adherence using multivariable analyses.
      Latent profile analysis was used to investigate whether patients can be
      categorized into groups with similar medication beliefs. Latent profile analysis
      categorizes individuals with similar profiles on a set of continuous variables
      into discrete groups represented by a categorical latent variable. Eight hundred
      and eleven patients enrolled in the British Association of Dermatologists
      Biologic Interventions Register were included. Six hundred and seventeen patients
      were using a self-administered systemic therapy; 22.4% were classified as "non
      adherent" (12% intentionally and 10.9% unintentionally). Patients using an oral
      conventional systemic agent were more likely to be non-adherent compared to those
      using etanercept or adalimumab (29.2% vs. 16.4%; P <= 0.001). Latent profile
      analysis supported a three-group model; all groups held strong beliefs about
      their need for systemic therapy but differed in levels of medication concerns.
      Group 1 (26.4% of the sample) reported the strongest concerns, followed by Group
      2 (61%), with Group 3 (12.6%) reporting the weakest concerns. Group 1 membership
      was associated with intentional non-adherence (odds ratio = 2.27, 95% confidence
      interval = 1.16-4.47) and weaker medication-taking routine or habit strength was
      associated with unintentional non-adherence (odds ratio = 0.92, 95% confidence
      interval = 0.89-0.96). Medication beliefs and habit strength are modifiable
      targets for strategies to improve adherence in psoriasis.

PMID- 29183732
TI  - Role of rotavirus vaccination on an emerging G8P[8] rotavirus strain causing an
      outbreak in central Japan.
AB  - BACKGROUND: In this study, we examined the effectiveness of RV1 and RV5 vaccines
      during an outbreak of G8P[8] rotavirus group A strain (G8P[8]-RVA). These
      vaccines were originally designed to provide protection against severe diseases
      caused by common circulating strains, whereas G8P[8]-RVA remains emerging strain
      and partially heterotypic to the vaccines. It is imperative to investigate
      vaccine effectiveness (VE) against G8P[8]-RVA because this strain appears to be
      predominant in recent years, particularly, in post-vaccine era. METHODS: RVA
      infection and genotypes were confirmed by polymerase chain reaction (PCR)
      followed by sequence-based genotyping. VE was determined during an outbreak of
      G8P[8]-RVA in Shizuoka Prefecture, Japan, in February-July 2017, retrospectively,
      by comparing vaccination status of children suffering from acute gastroenteritis
      (AGE) between 'PCR-positive' and 'PCR-negative' cases using conditional logistic
      regression adjusted for age. RESULTS: Among 80 AGE children, RVA was detected in
      58 (73%), of which 53 (66%) was G8P[8]-RVA. The clinical characteristics of
      G8P[8]-RVA and other RVA strains were identically severe. Notably, the attack
      rates of G8P[8]-RVA in vaccinated (61.1%) and unvaccinated (65.5%) children were
      almost similar. Indeed, no substantial effectiveness were found against G8P[8]
      RVA (VE, 14% [95% CI: -140% to 70%]) or other RVA strains (VE, 58% [95% CI: -20%
      to 90%]) for mild infections. However, these vaccines remained strongly effective
      against moderate (VE, 75% [95% CI: 1% to 40%]) and severe (VE, 92% [95% CI: 60%
      to 98%]) RVA infections. The disease severity including Vesikari score, duration
      and frequency of diarrhea, and body temperature were significantly lower in
      vaccinated children. CONCLUSIONS: This study demonstrates the effectiveness of
      current RV vaccines against moderate and severe, but not against the mild
      infections during an outbreak caused by unusual G8P[8]-RVA, which was virtually
      not targeted in the vaccines.

PMID- 29183734
TI  - Immune memory at 17-years of follow-up of a single dose of live attenuated
      hepatitis A vaccine.
AB  - BACKGROUND: In recent years, hepatitis A virus (HAV) infection has declined
      considerably in China, associated with wide deployment of HAV vaccines and
      improvement in socio-economic indicators. Towards the elimination of HA in the
      country, we assessed the duration and characteristics of immunity conferred by
      the widely used, locally manufactured HAV vaccine. METHODS: This is a
      longitudinal cohort study that followed recipients of a live attenuated HAV
      vaccine 17 years after the initial administration. Blood samples were collected
      from participants pre- and two-week post-booster HAV vaccine dose. Serum anti-HAV
      antibody was measured by ELISA method. Memory B and T cells were determined by
      ELISPOT and Flow Cytometry assays, respectively. RESULTS: A robust anamnestic
      response was observed two-week post-challenge. Both HAV-specific memory B cell
      and T cells remained, and responded quickly when re-encountering HAV. The
      magnitude of recall responses was present, regardless of the status of the serum
      anti-HAV antibody pre-booster. CONCLUSIONS: We demonstrated long-term immunity
      from the live attenuated HAV vaccine, including antibody persistence and
      immunological memory. Considering the conditions that make elimination of
      infectious diseases feasible, following polio, hepatitis A could be targeted for
      elimination in China.

PMID- 29183736
TI  - Immunotherapy in the Elderly.
AB  - CONTEXT: Immunotherapy has historic and contemporary presence in prostate,
      urothelial (UC), and renal cell (RCC) carcinomas. However, robust data on utility
      and generalizability of these treatments in older patients are lacking.
      OBJECTIVE: To systematically evaluate evidence regarding the efficacy and safety
      of immunotherapy in elderly patients with prostate cancer, UC, or RCC. EVIDENCE
      ACQUISITION: PubMed/Medline, Embase, Web of Knowledge, and Cochrane Library
      databases were searched up to October 2017 and according to the Preferred
      Reporting Items for Systematic Reviews and Meta-analyses statement. A narrative
      review of studies was performed. EVIDENCE SYNTHESIS: Twenty-one reports were
      included regarding prostate cancer (four studies), UC (eight), and RCC (nine). In
      prostate cancer, sipuleucel-T improves survival (median age >70 yr) and similar
      results were seen in the PROSTVAC phase 2 trial. Ipilimumab has not improved
      survival independent of age; data for programmed cell death 1 inhibition is
      evolving. In metastatic UC, >=50% of patients enrolled in pivotal checkpoint
      inhibitor studies were aged >=65 yr. Three studies reported similar objective
      response rates (ORRs) in patients aged <65 versus >=65 yr, whereas one study
      reported comparable ORRs in patients <80 versus >=80 yr. In metastatic RCC,
      cytokine studies showed no efficacy difference by age; one study reported more
      >=grade 3 toxicity in patients aged >=65 yr. One vaccine-based study suggests
      that older age was associated with shorter survival. The benefit of nivolumab in
      second-line therapy was more apparent for patients aged 65-<75 yr than for those
      aged >=75 yr. Across tumor subtypes, immunotherapy was well tolerated with
      minimal data stratifying toxicity by age. CONCLUSIONS: Contemporary immunotherapy
      has informed practice in genitourinary malignancies independent of patient age.
      Trial reporting of outcomes by age will be important to understand the
      generalizability of ongoing investigations for elderly patients. PATIENT SUMMARY:
      With the growing use of immunotherapy in genitourinary malignancies, benefits
      appear to apply independent of age. As the field advances, detailed reporting on
      outcomes and toxicities by age will be informative for both patients and
      physicians when discussing treatment options.

PMID- 29183735
TI  - Meningococcal carriage among a university student population - United States,
      2015.
AB  - OBJECTIVES: Several outbreaks of serogroup B meningococcal disease have occurred
      among university students in recent years. In the setting of high coverage of the
      quadrivalent meningococcal conjugate vaccine and prior to widespread use of
      serogroup B meningococcal vaccines among adolescents, we conducted surveys to
      characterize the prevalence and molecular characteristics of meningococcal
      carriage among university students. METHODS: Two cross-sectional oropharyngeal
      carriage surveys were conducted among undergraduates at a Rhode Island
      university. Isolates were characterized using slide agglutination, real-time
      polymerase chain reaction (rt-PCR), and whole genome sequencing. Adjusted
      prevalence ratios and 95% confidence intervals were calculated using Poisson
      regression to determine risk factors for carriage. RESULTS: A total of 1837
      oropharyngeal specimens were obtained from 1478 unique participants. Overall
      carriage prevalence was 12.7-14.6% during the two survey rounds, with 1.8-2.6%
      for capsular genotype B, 0.9-1.0% for capsular genotypes C, W, or Y, and 9.9
      10.8% for nongroupable strains by rt-PCR. Meningococcal carriage was associated
      with being male, smoking, party or club attendance, recent antibiotic use
      (inverse correlation), and recent respiratory infections. CONCLUSIONS: In this
      university setting, the majority of meningococcal carriage was due to
      nongroupable strains, followed by serogroup B. Further evaluation is needed to
      understand the dynamics of serogroup B carriage and disease among university
      students.

PMID- 29183737
TI  - Cross-platform single cell analysis of kidney development shows stromal cells
      express Gdnf.
AB  - The developing kidney provides a useful model for study of the principles of
      organogenesis. In this report we use three independent platforms, Drop-Seq,
      Chromium 10x Genomics and Fluidigm C1, to carry out single cell RNA-Seq (scRNA
      Seq) analysis of the E14.5 mouse kidney. Using the software AltAnalyze, in
      conjunction with the unsupervised approach ICGS, we were unable to identify and
      confirm the presence of 16 distinct cell populations during this stage of active
      nephrogenesis. Using a novel integrative supervised computational strategy, we
      were able to successfully harmonize and compare the cell profiles across all
      three technological platforms. Analysis of possible cross compartment
      receptor/ligand interactions identified the nephrogenic zone stroma as a source
      of GDNF. This was unexpected because the cap mesenchyme nephron progenitors had
      been thought to be the sole source of GDNF, which is a key driver of branching
      morphogenesis of the collecting duct system. The expression of Gdnf by stromal
      cells was validated in several ways, including Gdnf in situ hybridization
      combined with immunohistochemistry for SIX2, and marker of nephron progenitors,
      and MEIS1, a marker of stromal cells. Finally, the single cell gene expression
      profiles generated in this study confirmed and extended previous work showing the
      presence of multilineage priming during kidney development. Nephron progenitors
      showed stochastic expression of genes associated with multiple potential
      differentiation lineages.

PMID- 29183738
TI  - isGPT: An optimized model to identify sub-Golgi protein types using SVM and
      Random Forest based feature selection.
AB  - The Golgi Apparatus (GA) is a key organelle for protein synthesis within the
      eukaryotic cell. The main task of GA is to modify and sort proteins for transport
      throughout the cell. Proteins permeate through the GA on the ER (Endoplasmic
      Reticulum) facing side (cis side) and depart on the other side (trans side).
      Based on this phenomenon, we get two types of GA proteins, namely, cis-Golgi
      protein and trans-Golgi protein. Any dysfunction of GA proteins can result in
      congenital glycosylation disorders and some other forms of difficulties that may
      lead to neurodegenerative and inherited diseases like diabetes, cancer and cystic
      fibrosis. So, the exact classification of GA proteins may contribute to drug
      development which will further help in medication. In this paper, we focus on
      building a new computational model that not only introduces easy ways to extract
      features from protein sequences but also optimizes classification of trans-Golgi
      and cis-Golgi proteins. After feature extraction, we have employed Random Forest
      (RF) model to rank the features based on the importance score obtained from it.
      After selecting the top ranked features, we have applied Support Vector Machine
      (SVM) to classify the sub-Golgi proteins. We have trained regression model as
      well as classification model and found the former to be superior. The model shows
      improved performance over all previous methods. As the benchmark dataset is
      significantly imbalanced, we have applied Synthetic Minority Over-sampling
      Technique (SMOTE) to the dataset to make it balanced and have conducted
      experiments on both versions. Our method, namely, identification of sub-Golgi
      Protein Types (isGPT), achieves accuracy values of 95.4%, 95.9% and 95.3% for 10
      fold cross-validation test, jackknife test and independent test respectively.
      According to different performance metrics, isGPT performs better than state-of
      the-art techniques. The source code of isGPT, along with relevant dataset and
      detailed experimental results, can be found at https://github.com/srautonu/isGPT.

PMID- 29183739
TI  - Characterization of a novel GH36 alpha-galactosidase from Bacillus megaterium and
      its application in degradation of raffinose family oligosaccharides.
AB  - A novel alpha-galactosidase gene (agaB) from Bacillus megaterium 3-7 was cloned
      and expressed in Escherichia coli. The gene coded for a protein with 741 amino
      acids and a calculated molecular mass of 85.4kDa. The native structure of the
      recombined AgaB was determined to be a homotrimer. AgaB showed the highest
      identity of 57% with the characterized glycosyl hydrolase family 36 alpha
      galactosidase from Clostridium stercorarium F-9. The enzyme exhibited a specific
      activity of 362.6U/mg at 37 degrees C and pH 6.8. The enzyme showed strong
      resistance to proteases and great tolerance to galactose (Ki=12.5mM). AgaB
      displayed wide substrate specificity toward pNPGal, melibiose, raffinose and
      stachyose, with a Km of 0.42, 12.1, 17.0 and 25.4mM, respectively. Furthermore,
      AgaB completely hydrolyzed raffinose and stachyose present in soybean milk at 37
      degrees C within 4h when combined with trypsin. These favorable properties make
      AgaB a potential candidate for applications in the food and feed industries.

PMID- 29183740
TI  - Facile immobilization of Bacillus licheniformis gamma-glutamyltranspeptidase onto
      graphene oxide nanosheets and its application to the biocatalytic synthesis of
      gamma-l-glutamyl peptides.
AB  - For the practical application of Bacillus licheniformis gamma
      glutamyltranspeptidase (BlGGT), we illustrated a simple and efficient approach to
      fabricate a biocatalytic system by immobilizing the enzyme onto graphene oxide
      (GO) nanosheets via both non-covalent (GO-BlGGT) and covalent (GO/GA-BlGGT)
      bonds. The enzyme-loading capacity for the prepared GO/GA nanomaterial was 3.47
      mg/mg support, corresponding to 68.7% recovery of the initial activity. Native
      and enzyme-bound layered GOs were characterized by X-ray diffraction, followed by
      Raman and Fouier transform infrared spectroscopy, elemental analysis and
      thermogram analysis. As compared to the free form of BlGGT, the immobilized
      enzymes exhibited significantly higher activity, possibly due to the beneficial
      effect of the layered GO carrier. The kinetic behaviors of GO-BlGGT and GO/GA
      BlGGT were mostly consistent with those of free enzyme. The covalently
      immobilized enzyme had a comparable stability respective to free enzyme during a
      storage period of 30 days and could be recycled nine times with 45.3% retention
      of the initial activity. Besides, the biocatalytic synthesis of gamma-l-glutamyl
      phenylalanine and gamma-l-glutamyl-leucine by immobilized enzymes resulted in the
      product yield of more than 31%. Taken together, these results suggest that the
      facile strategy is an economical means of depositing bioactive enzymes upon GO
      nanosheets for BlGGT-mediated biocatalysis.

PMID- 29183741
TI  - Arginine as an Excipient for Protein Freeze-Drying: A Mini Review.
AB  - Successful development of marketable freeze-dried protein formulations requires
      adequate stabilization of the active biopharmaceutical ingredient. The choice of
      a stabilizer must therefore be based on sound knowledge of the physical and
      chemical properties of the excipients and specific needs of the protein
      component. Amino acids, such as arginine, have exhibit cryo- and lyoprotective
      effects similar to those of sugars and polymers and may therefore be considered
      to be an alternative approach to these established formulation strategies. The
      chemical structure and physicochemical characteristics of arginine are unique
      among amino acids and can provide additional benefits to freeze-dried protein
      formulations with regard to liquid and solid-state stability. This mini review
      provides a brief summary of research focused on the application of arginine in
      freeze-dried protein pharmaceuticals, including a discussion of its basic
      physical and chemical attributes as well as thermal behavior in the frozen and
      solid states. Mechanisms contributing to solid-state stabilization by arginine
      are discussed in the context of available stability studies on arginine
      containing protein formulations. This mini review seeks to deepen the
      understanding of the opportunities and challenges associated with arginine-based
      preparations for freeze-dried protein pharmaceuticals.

PMID- 29183742
TI  - Curcumin Cocrystal Micelles-Multifunctional Nanocomposites for Management of
      Neurodegenerative Ailments.
AB  - Curcumin, a potent antioxidant polyphenol with neuroprotective and antiamyloid
      activities, has significant potential in the treatment of neurodegenerative
      disorders such as Alzheimer's disease. However, its clinical translation is
      delayed due to poor bioavailability. For effective use of curcumin in Alzheimer's
      disease, it is imperative to increase its bioavailability with enhanced delivery
      at a therapeutic site that is, brain. With this objective, pharmaceutical
      cocrystals of curcumin were developed and incorporated in micellar nanocarriers
      for nose-to-brain delivery. For cocrystals, an antioxidant hydrophilic coformer
      was strategically selected using molecular modeling approach. The cocrystals were
      formulated using a planetary ball mill, and the process was optimized using 32
      factorial design followed by characterization using differential scanning
      calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy
      analysis. The cocrystal micelles exhibited globule size of 28.79 +/- 0.86 nm.
      Further, curcumin cocrystal and co-crystal micelles exhibited a significantly low
      (p value <0.01) IC50 concentration for antioxidant activity as compared to
      curcumin corroborating superior antioxidant performance. In vivo studies revealed
      about 1.7-fold absolute bioavailability of curcumin cocrystal micelles with Cmax
      of 1218.38 +/- 58.11 ng/mL and showed significantly high brain distribution even
      beyond 6 hours of dosing. Thus, the studies confirmed enhanced bioavailability,
      higher brain uptake, retention, and delayed clearance with curcumin cocrystal
      micellar nanocarriers.

PMID- 29183743
TI  - Development and Characterization of Chitosan Cross-Linked With Tripolyphosphate
      as a Sustained Release Agent in Tablets, Part I: Design of Experiments and
      Optimization.
AB  - Certain issues with the use of particles of chitosan (Ch) cross-linked with
      tripolyphosphate (TPP) in sustained release formulations include inefficient drug
      loading, burst drug release, and incomplete drug release. Acetaminophen was added
      to Ch:TPP particles to test for advantages of drug addition extragranularly over
      drug addition made during cross-linking. The influences of Ch concentration,
      Ch:TPP ratio, temperature, ionic strength, and pH were assessed. Design of
      experiments allowed identification of factors and 2-factor interactions that have
      significant effects on average particle size and size distribution, yield, zeta
      potential, and true density of the particles, as well as drug release from the
      directly compressed tablets. Statistical model equations directed production of a
      control batch that minimized span, maximized yield, and targeted a t50 of 90 min
      (sample A); sample B that differed by targeting a t50 of 240-300 min to provide
      sustained release; and sample C that differed from sample B by maximizing span.
      Sample B maximized yield and provided its targeted t50 and the smallest average
      particle size, with the higher zeta potential and the lower span of samples B and
      C. Extragranular addition of a drug to Ch:TPP particles achieved 100% drug
      loading, eliminated a burst drug release, and can accomplish complete drug
      release.

PMID- 29183744
TI  - Alginate-Based Hydrogel Containing Minoxidil/Hydroxypropyl-beta-Cyclodextrin
      Inclusion Complex for Topical Alopecia Treatment.
AB  - Cutaneous minoxidil (MXD) formulations were developed with the intent to reduce
      the side effects of the cosolvents propylene glycol and ethanol, frequently used
      in commercial MXD solutions. Completely aqueous alginate-based hydrogels were
      investigated and MXD aqueous solubility was improved using inclusion complexes
      with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) at 2 different molar
      substitution degree (MS), namely 0.65 and 0.85. HP-beta-CD MS 0.65 was selected
      for its improved solubilizing ability toward MXD. At concentration of 39% w/v,
      this cyclodextrin increased the intrinsic aqueous solubility of MXD of about 22
      fold. The calculated complexation constant was 2309 +/- 20 M-1, and the inclusion
      process was spontaneous and enthalpically driven. Nuclear magnetic resonance
      studies (Job plot, 1H, 2D correlations spectroscopy, nuclear overhauser effect
      spectroscopy, and rotating-frame overhauser enhancement spectroscopy) confirmed
      the stoichiometry 1:1 between MXD and HP-beta-CD providing information about the
      exact geometry of the inclusion complex. Rheological and in vitro release studies
      performed on the formulation loaded with MXD 3.5% w/w proved that the inclusion
      complex increased the viscosity of the hydrogel modulating the release of the
      free drug. Furthermore, the hydrogel formulation facilitate MXD to permeate into
      the skin and did not damage epidermis, suggesting that these completely aqueous
      MXD delivery systems can be proposed as alternative formulations to commercial
      solutions.

PMID- 29183745
TI  - Comparison of [17(20)E]-21-Norpregnene oxazolinyl and benzoxazolyl derivatives as
      inhibitors of CYP17A1 activity and prostate carcinoma cells growth.
AB  - Four new 4,5-dihydro-1,3-oxazole, and four new benzo-[d]-oxazole derivatives of
      [17(20)E]-21-norpregnene, differing in the structure of steroid moiety, were
      synthesized and evaluated for their potency to inhibit 17alpha-hydroxylase/17,20
      lyase (CYP17A1) activity. Among new compounds, the only oxazolinyl derivative
      comprising 5-oxo-4,5-seco-3-yn- moiety potently inhibited CYP17A1. Binding modes
      of the oxazolinyl derivatives of [17(20)E]-21-norpregnene were analyzed by
      molecular dynamics simulations, and model of alternate, water-bridged type II
      interaction was proposed for these compounds. Eight new compounds, together with
      two CYP17A1-inhibiting oxazolinyl derivatives synthesized earlier, abiraterone
      and galeterone were evaluated for their potency to inhibit prostate carcinoma PC
      3 and LNCaP cells growth. Oxazolinyl and benzoxazolyl derivatives comprising
      3beta-hydroxy-5-ene moieties potently inhibited prostate carcinoma cell growth;
      inhibitory potencies of 3-oxo-4-en- and 5-oxo-4,5-seco-3-yn- derivatives were
      significantly lower.

PMID- 29183746
TI  - Assessment of the anti-snakebite properties of extracts of Aniba fragrans Ducke
      (Lauraceae) used in folk medicine as complementary treatment in cases of
      envenomation by Bothrops atrox.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of leaves and bark of Aniba fragrans are
      used as tea (decoction) to treat snakebites in communities in the Brazilian
      Amazon. The aqueous extract of the leaves of A. fragrans has been proven to be
      effective against Bothrops venom, but only when pre-incubated with the venom.
      This study sought to assess the potential of different types of extract of this
      species to inhibit the biological activities of Bothrops atrox venom (BaV) when
      used the same way as in folk medicine. The main classes of secondary metabolites
      and the concentrations of phenolics in the extracts were also determined.
      MATERIALS AND METHODS: Four types of extract of A. fragrans were prepared:
      aqueous extract of the leaf (AEL), aqueous extract of the bark (AEB),
      hydroalcoholic leaf extract (HLE) and extract of the residue from
      hydrodistillation of the leaf (ERHL). The phytochemical profiles of the aqueous
      extracts were determined using thin layer chromatography (TLC), and the
      concentrations of phenolics were measured by colorimetric assays. To investigate
      the potential of the extracts to inhibit the biological activities of BaV, in
      vitro tests for antiphospholipase and antifibrinolytic activities were performed.
      In vivo tests for antihemorrhagic and antidefibrinating activities were also
      carried out, as well as antimicrobial tests for activity against the main
      bacteria found in the oral cavity of snakes. Interaction between the extracts and
      the proteins in BaV was assessed by electrophoresis (SDS-PAGE) and Western blot
      (WB). The cytotoxicity of the extracts was assessed in a strain of MRC-5 human
      fibroblasts. RESULTS: Terpenoids, flavonoids and condensed and hydrolysable
      tannins were detected in all the extracts. Metabolites such as coumarins, fatty
      acids and alkaloids were present in some extracts but not in others, indicating
      different phytochemical profiles. Phenolics content varied between extracts, and
      there were more tannins in AEB and HLE. In the in vitro tests, the extracts
      inhibited the phospholipase and fibrinolytic activities of BaV in the two ratios
      of venom to extract used. HLE exhibited effective antimicrobial action as it
      inhibited growth of 11 of the 15 bacteria investigated, including Morganella
      morganii, the main bacteria described in the oral cavity of snakes. The extracts
      failed to inhibit the defibrinating activity of BaV, and only the Bothrops
      antivenom had a significant effect (96.1%) on this activity. BaV-induced
      hemorrhage was completely inhibited by AEL and AEB when the pre-incubation
      (venom:extract) protocol was used. When administered orally, as in folk medicine,
      both AEB and AEL produced significant inhibition of hemorrhagic activity (maximum
      inhibition 46.5% and 39.2%, respectively). SDS-PAGE and WB of the extracts pre
      incubated with BaV showed that the main proteins in the venom had been
      precipitated by the extracts. None of the four extracts showed cytotoxic effects
      in the tests carried out with a human fibroblast cell line. CONCLUSION: In
      addition to being effective in reducing hemorrhage when administered orally, the
      extracts displayed a high antimicrobial potential against microorganisms involved
      in secondary infections at the site of the snakebite. Once the extracts have been
      tested in accordance with the appropriate regulations, this species could
      potentially be used to produce a phytomedicine for complementary treatment of the
      secondary infections due to bacteria that aggravate the local signs and symptoms
      after snakebite envenomation.

PMID- 29183747
TI  - Anticonvulsant effect of the hydroethanolic leaf extract of Psydrax subcordata
      (DC.) Bridson in murine models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Psydrax subcordata (DC.) Bridson is a tropical
      medicinal plant used traditionally for the management of epilepsy. However, there
      is little scientific evidence to support its use. AIM OF STUDY: The current study
      investigated the anticonvulsant properties of the hydroethanolic leaf extract of
      Psydrax subcordata (PSE) in animal models. MATERIALS AND METHODS: The
      anticonvulsant effects were evaluated in mouse models of acute seizures
      (pentylenetetrazole-, picrotoxin-, 4-aminopyridine-, strychnine- and maximal
      electroshock-induced seizure tests) and status epilepticus (Lithium/pilocarpine
      induced SE). The role of GABAergic mechanisms in the actions of the extract was
      also examined by pre-treatment of animals with flumazenil in the
      pentylenetetrazole test. RESULTS: The extract (30, 100 and 300mg/kg, p.o.)
      significantly delayed the onset and decreased the duration and frequency of
      pentylenetetrazole- and picrotoxin-convulsions. PSE also reduced the duration of
      tonic hind limb extensions in the maximal electroshock-induced seizure test.
      Furthermore, PSE pre-treatment significantly delayed the onset of seizures and
      improved survival in the 4-aminopyridine-induced seizure test. In the strychnine
      induced seizure test, PSE treatment did not significantly affect the latency to
      convulsions and time until death when compared to controls. PSE exhibited
      anticonvulsant effects in the lithium/pilocarpine test by delaying the onset of
      seizures and status epilepticus as well as reducing the severity of seizures and
      mortality of mice. Again, the anticonvulsant effect of PSE (100mg/kg, p.o.) was
      blocked by pre-treatment with flumazenil in the PTZ test. CONCLUSION: PSE has
      anticonvulsant activity in animal models, and this effect may be mediated, at
      least partly, through GABAergic mechanisms.

PMID- 29183748
TI  - Antimicrobial stewardship program in critical care medicine: What is going on?
      Who gives more?

PMID- 29183749
TI  - Heterologous transporter expression for improved fatty alcohol secretion in
      yeast.
AB  - The yeast Saccharomyces cerevisiae is an attractive host for industrial scale
      production of biofuels including fatty alcohols due to its robustness and
      tolerance towards harsh fermentation conditions. Many metabolic engineering
      strategies have been applied to generate high fatty alcohol production strains.
      However, impaired growth caused by fatty alcohol accumulation and high cost of
      extraction are factors limiting large-scale production. Here, we demonstrate that
      the use of heterologous transporters is a promising strategy to increase fatty
      alcohol production. Among several plant and mammalian transporters tested, human
      FATP1 was shown to mediate fatty alcohol export in a high fatty alcohol
      production yeast strain. An approximately five-fold increase of fatty alcohol
      secretion was achieved. The results indicate that the overall cell fitness
      benefited from fatty alcohol secretion and that the acyl-CoA synthase activity of
      FATP1 contributed to increased cell growth as well. This is the first study that
      enabled an increased cell fitness for fatty alcohol production by heterologous
      transporter expression in yeast, and this investigation indicates a new potential
      function of FATP1, which has been known as a free fatty acid importer to date. We
      furthermore successfully identified the functional domain of FATP1 involved in
      fatty alcohol export through domain exchange between FATP1 and another
      transporter, FATP4. This study may facilitate a successful commercialization of
      fatty alcohol production in yeast and inspire the design of novel cell factories.

PMID- 29183750
TI  - Pheromone-inducible expression vectors for fission yeast Schizosaccharomyces
      pombe.
AB  - The fission yeast Schizosaccharomyces pombe is an attractive host for
      heterologous gene expression. However, expression systems for industrially viable
      large-scale fermentations are scarce. Several inducible expression vectors for S.
      pombe have been reported, with the strong thiamine-repressible nmt1+ promoter or
      derivatives thereof most commonly employed. Previously, the promoter regions of
      the genes sxa2+ and rep1+ were utilized to couple pheromone signaling to the
      expression of reporter genes for quantitative assessment of the cellular response
      to mating pheromones. Here, we exploit these promoters to serve as highly
      effective, plasmid-based inducible expression systems for S. pombe. Simply by
      adding synthetic P-factor pheromone, both promoters conferred 50-60% higher peak
      expression levels than the nmt1+ promoter. Full induction was significantly
      faster than observed for nmt1+-based expression platforms. Furthermore, the sxa2+
      promoter showed very low basal activity and an overall 584-fold induction by
      synthetic P-factor pheromone. The dose-response curves of both promoters were
      assessed, providing the opportunity for facile tuning of the expression level by
      modulating P-factor concentration. Since the expression plasmids relying on the
      sxa2+ and rep1+ promoters require neither medium exchange nor glucose/thiamine
      starvation, they proved to be very convenient in handling. Hence, these
      expression vectors will improve the palette of valuable genetic tools for S.
      pombe, applicable to both basic research and biotechnology.

PMID- 29183751
TI  - Impact of Work-Related Burn Injury on Social Reintegration Outcomes: A Life
      Impact Burn Recovery Evaluation (LIBRE) Study.
AB  - OBJECTIVE: To examine differences in long-term social reintegration outcomes for
      burn survivors with and without work-related injuries. DESIGN: Cross-sectional
      survey. SETTING: Community-dwelling burn survivors. PARTICIPANTS: Burn survivors
      (N=601) aged >=18 years with injuries to >=5% total body surface area or burns to
      critical areas (hands, feet, face, or genitals). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The Life Impact Burn Recovery Evaluation Profile was used
      to examine the following previously validated 6 scale scores of social
      participation: Family and Friends, Social Interactions, Social Activities, Work
      and Employment, Romantic Relationships, and Sexual Relationships. RESULTS: Older
      participants, those who were married, and men were more likely to be burned at
      work (P<.01). Burn survivors who were injured at work scored significantly lower
      on the Work and Employment scale score after adjusting for demographic and
      clinical characteristics (P=.01). All other domain scale scores demonstrated no
      significant differences between groups. Individuals with work-related injuries
      scored significantly worse on 6 of the 19 items within the Work and Employment
      scale (P<.05). These individuals were more likely to report that they were afraid
      to go to work and felt limited in their ability to perform at work. CONCLUSIONS:
      Burn survivors with work-related injuries report worse work reintegration
      outcomes than those without work-related injuries. Identification of those at
      higher risk for work reintegration challenges after burn injury may enable
      survivors, providers, employers, and insurers to better use appropriate resources
      to promote and target optimal employment outcomes.

PMID- 29183752
TI  - One-Year Comparison of a Community-Based Exercise Program Versus a Day Hospital
      Based Exercise Program on Quality of Life and Mental Health in Severely Burned
      Children.
AB  - OBJECTIVE: To compare the effects of long-term psychosocial functioning and
      mental health of a "day hospital"-based exercise program (DAYEX) versus a
      community-based exercise program (COMBEX). DESIGN: A prospective design that
      consisted of 2 groups (DAYEX and COMBEX). SETTING: A children's hospital
      specialized in burn care. PARTICIPANTS: Patients (N=18; DAYEX [n=9], COMBEX
      [n=9]) were assessed at intensive care unit discharge and up to 1 year postburn.
      INTERVENTIONS: The Child Health Questionnaires (CHQ-Child Form [CHQ-CF87] and CHQ
      Parent Form [CHQ-PF28]) were used to assess changes in quality of life from
      discharge to 1 year postburn. MAIN OUTCOME MEASURES: CHQ-PF28 and CHQ-CF87.
      RESULTS: Demographic characteristics and total body surface area burned were
      similar in both groups. Length of hospital stay was significant in the COMBEX
      group. CHQ-CF87 and CHQ-PF28 documented significant improvements in both groups
      between discharge and 1 year. Significance was evident in Physical Functioning,
      Bodily Pain, Self-Esteem, Change in Health, and Family Activities. CHQ-CF87
      showed improvement in Family Cohesion in COMBEX more than DAYEX. CHQ-PF28 showed
      improvement in Role/Social Limitations-Emotional, Bodily Pain, and Family
      Activities in COMBEX more than DAYEX. CONCLUSIONS: The proposed COMBEX program is
      feasible and beneficial physically, psychosocially, and mentally. The results
      show some improvements in the COMBEX group in optimizing function and health in
      severely burned children. The COMBEX group performed at least as well as the
      DAYEX group. Larger-scale studies are needed to validate current findings.

PMID- 29183753
TI  - Xanthine-derived KMUP-1 reverses glucotoxicity-activated Kv channels through the
      cAMP/PKA signaling pathway in rat pancreatic beta cells.
AB  - Hyperglycemia-associated glucotoxicity induces beta-cell dysfunction and a
      reduction in insulin secretion. Voltage-dependent K+ (Kv) channels in pancreatic
      beta-cells play a key role in glucose-dependent insulin secretion. KMUP-1, a
      xanthine derivative, has been demonstrated to modulate Kv channel activity in
      smooth muscles; however, the role of KMUP-1 in glucotoxicity-activated Kv
      channels in pancreatic beta-cells remains unclear. In this study we examined the
      mechanisms by which KMUP-1 could inhibit high glucose (25 mM) activated Kv
      currents (IKv) in pancreatic beta-cells. Pancreatic beta-cells were isolated from
      Wistar rats and IKv was monitored by perforated patch-clamp recording. The peak
      IKv in high glucose-treated beta-cells was ~1.4-fold greater than for normal
      glucose (5.6 mM). KMUP-1 (1, 10, 30 MUM) prevented high glucose-stimulated IKv in
      a concentration-dependent manner. Reduction of high glucose-activated IKv was
      also found for protein kinase A (PKA) activator 8-Br-cAMP (100 MUM).
      Additionally, KMUP-1 (30 MUM) current inhibition was reversed by the PKA
      inhibitor H-89 (1 MUM). Otherwise, pretreatment with the PKC activator or
      inhibitor had no effect on IKv in high glucose exposure. In conclusion,
      glucotoxicity-diminished insulin secretion was due to IKv activation. KMUP-1
      attenuated high glucose-stimulated IKv via the PKA but not the PKC signaling
      pathway. This finding provides evidence that KMUP-1 might be a promising agent
      for treating hyperglycemia-induced insulin resistance.

PMID- 29183754
TI  - Nitroxide Tempol down-regulates kinase activities associated with NADPH oxidase
      function in phagocytic cells and potentially decreases their fungicidal response.
AB  - AIMS: The identification of novel targets to control inflammation in humans is
      probably the primary challenge that impairs the development of new anti
      inflammatory drugs. Therefore, the modulation of intracellular signaling pathways
      in phagocytes may be an interesting means of achieving this goal. However, this
      change to signaling can compromise the host's susceptibility to invading
      pathogens. We investigated whether the antioxidant nitroxide Tempol regulates the
      activity of kinases associated with the production of oxidants in neutrophils,
      which affects the fungicidal capability of these cells. MAIN METHODS: The effects
      of Tempol on PMA- or fMLP-activated neutrophils were examined by oxygen
      consumption as an index of the oxidative burst, a release of extracellular and
      total Reactive Oxygen Species (ROS) by chemiluminescence, kinase activities
      through analysis of ATP consumption during enzyme activities and the dot blot
      immunoassay and, finally, by neutrophil capacity of killing Candida albicans. KEY
      FINDINGS: Tempol significantly inhibited the neutrophil oxidative burst in a
      concentration-dependent manner and decreased oxygen consumption (IC50 = 45 MUM)
      and extracellular/total ROS formation with an increase on the lag period
      response. In addition, Tempol inhibited neutrophil kinase activities (i.e., a
      decrease in protein phosphorylation) elicited through different biochemical
      pathways and consequently impaired the fungicidal activity of these cells.
      SIGNIFICANCE: Although Tempol has potential anti-inflammatory activity that acts
      on different intracellular pathways (such as those involving kinases),
      researchers should be cautious, since this nitroxide down-regulated oxidants
      production and the fungicidal response of neutrophils.

PMID- 29183755
TI  - Structural determination, distribution, and physiological actions of ghrelin in
      the guinea pig.
AB  - We identified guinea pig ghrelin (gp-ghrelin), and examined its distribution and
      physiological actions in the guinea-pig. Gp-ghrelin is a 28-amino acid peptide
      (GASFR SPEHH SAQQR KESRK LPAKI QPR); seven amino acids are different from that of
      rat ghrelin at positions 2, 5, 10, 11, 19, 21, and 25, which include the
      conserved region known in mammals. The third serine residue is mainly modified by
      n-decanoyl acid. Both gp-ghrelin and rat ghrelin increased intracellular Ca2+
      concentration of HEK293 cells expressing guinea pig growth hormone secretagogue
      receptor 1a (GHS-R1a), and the affinity of gp-ghrelin was slightly higher than
      that of rat ghrelin. In addition, gp-ghrelin was also effective in CHO cells
      expressing rat GHS-R1a with similar affinity to that of rat ghrelin. Gp-ghrelin
      mRNA was predominantly expressed in the stomach, whereas the expression levels in
      other organs was low. High levels of GHS-R1a mRNA expression were observed in the
      pituitary, medulla oblongata, and kidney, while medium levels were noted in the
      thalamus, pons, olfactory bulb, and heart. Immunohistochemistry identified gp
      ghrelin-immunopositive cells in the gastric mucosa and pancreas. Intraperitoneal
      injection of gp-ghrelin increased food intake in the guinea pig. Gp-ghrelin did
      not cause any mechanical responses in isolated gastrointestinal smooth muscles in
      vitro, similar to rat ghrelin. In conclusion, the N-terminal structures that are
      conserved in mammals were different in gp-ghrelin. Moreover, the functional
      characteristics of gp-ghrelin, other than its distribution, were dissimilar from
      those in other Rodentia.

PMID- 29183756
TI  - Activiated galanin receptor 2 attenuates insulin resistance in skeletal muscle of
      obese mice.
AB  - The results of our and other's studies showed that activation of galanin receptor
      1 could mitigate insulin resistance via promoting glucose transporter 4 (GLUT4)
      expression and translocation in the skeletal muscle of rats. But no literature
      are available regarding the effect of galanin receptor 2 (GALR2) on insulin
      resistance in skeletal muscle of type 2 diabetes. Herein, in this study we
      intended to survey the effect of GALR2 and its signal mechanisms in the mice with
      high fat diet-induced obese. The mice were intraperitoneally injected with
      vehicle, GALR2 agonist M1145 and antagonist M871 respectively once a day for
      continuous 21 days. The skeletal muscles were processed for determination of
      glucose uptake, and GLUT4 mRNA and protein expression levels. The PGC-1alpha,
      AKT, p38MAPK, AS160, pAKT, pP38MAPK and pAS160 expression levels were
      quantitatively assessed too. We found that pharmacological activation of GALR2
      enhanced energy expenditure, and increased GLUT4 expression and translocation in
      skeletal muscle of mice during high-fat diet regimens. Activation of GALR2
      alleviated insulin resistance through P38MAPK/PGC-1alpha/GLUT4 and
      AKT/AS160/GLUT4 pathway in the skeletal muscle of mice. Overall, these results
      identify that GALR2 is a regulator of insulin resistance and activation of GALR2
      represents a promising strategy against obesity-induced insulin resistance.

PMID- 29183757
TI  - Virulence and resistance on various pathogens mediated by mobile genetic
      integrons via high flux assays.
AB  - BACKGROUND: Recognized as a resistance mechanism responsible for the emergence
      and prevalence of antimicrobial resistance, integron is widely distributed and
      spread among clinical microorganisms and play a key role in the dissemination of
      such antimicrobial resistance, which may eventually contribute to the unleashing
      of "Super Bugs" In this study, detection assays based on loop-mediated isothermal
      amplification (LAMP) methodologies targeting on class 1 to class 3 integrase
      genes was developed and evaluated. METHODS: LAMP methodology was employed to
      develop novel detection assays on class 1, 2 and 3 integrons. Firstly, this
      protocol was specifically designed to detect such integrons by targeting
      integrase genes intI1, intI2 and intI3. Development, evaluation and optimization
      of such LAMP assays was studied, including the reaction temperature, volumn,
      time, sensitivity and specificity of both primers and targets. A total of 1082
      strains, including 397 integron positive and 685 integron negative
      microorganisms, were included for the application verification of the established
      LAMP assays. RESULTS: The indispensability of each primer was confirmed, and the
      optimal amplification was obtained under 63  degrees C for 45 min, with 25 MUl
      reaction found to be the most cost-efficient volume. As application was
      concerned, all of the 397 integron-positive isolates yielded positive amplicons
      and other 685 integron-negative bacteria were negative for the integron-LAMP
      assays, revealing totaling 100% detection rate and specificity. CONCLUSIONS: The
      established integron-LAMP assays was demonstrated to be a valid and rapid
      detection method for integrons screening, which may aid in both the laboratory
      and clinical integron screening for microorganisms.

PMID- 29183758
TI  - Evaluation of intrinsic and acquired immune cells infiltration in kidney and
      spleen of the mice infected with systemic candidiasis and treated with chloroform
      fraction of Zataria Multiflora Boiss.
AB  - BACKGROUND AND AIMS: Despite the use of antifungal drugs, the visceral
      candidiasis is associated with a high mortality rate. The aims of this study were
      an evaluation of intrinsic and acquired immune cells infiltration in kidney and
      spleen of the mice infected with systemic candidiasis and treated with chloroform
      fraction of Zataria Multiflora Boiss. MATERIALS AND METHODS: Candida albicans (C.
      albicans) ATCC10231 clinical standard strain was isolated. C. albicans LD50 was
      determined. The laboratory animal (BALB/C mouse) infection with the visceral
      candidiasis was performed. The kidney and spleen tissues were stained with PAS
      and prepared for confirmation under the microscope. The Zataria Multiflora Boiss
      (Shiraz thyme) was prepared and the effects on the infected group were assessed.
      The kidney and spleen mononuclear cells (MNCs) were prepared and the flow
      cytometry technique was performed for the assessment of Th1, Th17, and Treg
      cells. RESULTS: The LD50 and LD totals were 1.5 * 108 and 2 * 108 Yeast/0.1 ml,
      respectively. In mice which had a drug intervention, including chloroform
      fraction of Zataria Multiflora Boiss, thymol, carvacrol or fluconazole, fungal
      purification was greater in the spleen than in the kidney. Among those mice
      without medication intervention, fungal clearance was higher in the kidney. The
      highest percentage of TH1 cells was in group 1 and then group 4 and in groups 2
      and 3 respectively. Moreover, there was a significant difference between groups 4
      and 5 and also 6 and 7. The percentage of TH1 cells in the spleen MNCs was higher
      than that of the kidney cells, which is the difference between the groups except
      for group 7. The percentage of TH17 cells in the kidney and spleen of all drug
      receiving groups exhibited a significant increase compared to groups 6 and 7. The
      percentage of Treg cells in the kidney and the spleen only in the extract
      receiving group had a significant decrease compared to the non-drug receiving
      group and the other groups receiving group depicted no significant difference in
      the percentage of Treg cells. CONCLUSION: In addition to the direct effect on the
      fungus proven in vitro, the extract exhibits immunosuppressive effects, and thus
      can degrade the fungus through this way. The results demonstrated that the
      fraction of Zataria Multiflora Boiss can be considered as a powerful alternative
      to C. albicans therapy along with other therapies.

PMID- 29183759
TI  - Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in
      normal human keratinocytes.
AB  - Benzophenone-3 (BP-3), which is extensively used in organic sunscreen, has
      phototoxic potential in human skin. Phosphodiesterase 4B (PDE4B) has a well
      established role in inflammatory responses in immune cells. Currently, it is
      unknown if PDE4B is associated with BP-3-induced phototoxicity in normal human
      keratinocytes (NHKs). We found that BP-3 significantly increased PDE4B expression
      in ultraviolet B (UVB)-irradiated NHKs. Notably, BP-8, a sunscreen agent that
      shares the 2-hydroxy-4-methoxyphenyl methanone moiety with BP-3, also upregulated
      PDE4B expression in NHKs. Upon UVB irradiation, BP-3 upregulated the expression
      of pro-inflammatory factors, such as prostaglandin endoperoxide synthase 2, tumor
      necrosis factor alpha, interleukin 8, and S100A7, and downregulated the level of
      cornified envelope associated proteins, which are important in the development of
      the epidermal permeability barrier. The additive effects of UVB-activated BP-3 on
      the expression of both pro-inflammatory mediators and cornified envelope
      associated proteins were antagonized by treatment with the PDE4 inhibitor
      rolipram. The BP-3 and UVB co-stimulation-induced PDE4B upregulation and its
      association with the upregulation of pro-inflammatory mediators and the
      downregulation of epidermal differentiation markers were confirmed in a
      reconstituted three dimensional human epidermis model. Therefore, PDE4B has a
      role in the mechanism of BP-3-induced phototoxicity.

PMID- 29183760
TI  - Th17 pathway in recent-onset autoimmune diabetes.
AB  - AIMS: Evaluate the participation of IL-17 pathway in T1D pathogenesis. T helper
      17 cells are potent, highly inflammatory cells that produce interleukin 17A (IL
      17A), considered a mediator of various immune disorders. However, their role in
      Type 1 diabetes (T1D) pathogenesis in humans is not totally elucidated. METHODS:
      The expression of IL-17 Receptor A (IL-17RA) in peripheral T lymphocytes and IL
      17A serum levels in recent-onset patients with T1D were compared with healthy
      controls. IL-17A gene variants were evaluated in a greater cohort. RESULTS:
      Patients with recent-onset T1D (less than 6 months of diagnosis) exhibited lower
      expression of IL-17RA in CD3+ T (% of cells = 31.3% * 43.6%; p = .041) and CD4+ T
      cells (11.1% * 25.2%; p = .0019) and lower number of IL-17RA in CD4+ T cells (MFI
      = 1.16 * 4.56; p = .03) than controls. IL-17RA expression in CD8+ T cells and IL
      17A serum levels were similar in both groups. The coding regions and boundary
      intron sequences of IL17A were sequenced. Seventeen allelic variants, including
      three novel variants in exon 3 (3'UTR n) were identified, but no one was
      associated with T1D susceptibility, as well as the resulting haplotypes and
      diplotypes. The expression of IL-17RA was not correlated with metabolic variables
      (glucose and HbA1c levels) or pancreatic autoantibodies titers. CONCLUSIONS: The
      lower expression of IL-17RA in CD3+ and CD4+ T cells suggests a reduced effect of
      IL-17A in immune response of recent-onset T1D patients, at least at peripheral
      tissues. IL-17A allelic variants were not related with T1D susceptibility.

PMID- 29183761
TI  - Calculation by GAMOS/Geant4 simulation of cellular energy distributions from
      alpha and lithium-7 particles created by BNCT.
AB  - Monte Carlo (MC) has demonstrated to be a suitable technique to evaluate the
      microdosimetric parameters at the cellular level for Boron Neutron Capture
      Therapy (BNCT). The objectives of the current study are first to validate GAMOS
      MC codes with different Geant4 physics models for the range calculations of alpha
      particles. Once the proper physics is selected, the second objective is to
      determine the distributions of deposited energy in cellular medium originated by
      alpha and lithium-7 particles induced by 10B(n,alpha)7Li.

PMID- 29183762
TI  - Distribution of Heavy Metals in Core Marine Sediments of Coastal East Malaysia by
      Instrumental Neutron Activation Analysis and Inductively Coupled Plasma
      Spectroscopy.
AB  - Fifty-five core marine sediments from three locations at South China Sea and one
      location each at Sulu Sea and Sulawesi Sea of coastal East Malaysia were analyzed
      for heavy metals by instrumental neutron activation analysis and inductively
      coupled plasma mass spectroscopy. The enrichment factor and the modified degree
      of contamination were used to calculate the anthropogenic and pollution status of
      the elements in the samples. The enrichment factor of As, Cd, Cr, Cu, Ni, Pb, and
      Zn varied from 0.42-4.26, 0.50-2.34, 0.31-0.82, 0.20-0.61, 0.91-1.92, 0.23-1.52,
      and 0.90-1.28, respectively, with the modified degree of contamination values
      below 0.6. Comparative data showed that coastal East Malaysia has low levels of
      contamination.

PMID- 29183763
TI  - A rare case of esophageal lymphoepithelial carcinoma without Epstein-Barr virus
      infection.

PMID- 29183764
TI  - Clinical outcome of portal vein thrombosis in patients with digestive cancers: A
      large AGEO multicenter study.
AB  - INTRODUCTION: Management of portal vein thrombosis (PVT) in cancer patients
      remains discussed. AIMS: The objective of this multicenter retrospective study
      was to investigate the management and outcome of PVT in patients with digestive
      cancers other than hepatocellular carcinoma (HCC). METHOD: Main inclusion
      criteria were trunk or branch PVT in patients with locally advanced or metastatic
      digestive cancers. Predictive factors of bleeding and overall survival (OS) were
      evaluated in univariate and multivariate analysis. RESULTS: Between 2012 and
      2016, 118 patients with PVT and digestive cancers were identified. The majority
      had a pancreatic cancer (50%). Sixty-six percent of patients had trunk PVT
      location. Endoscopic screening of portal hypertension was performed in only 7
      patients (1%) and 5 had esophageal varices. Gastrointestinal bleeding occurred in
      22 patients (19%) and 12 patient deaths (17%) were related to a gastrointestinal
      hemorrhage. Metastatic disease (HR=2.83 [95%CI 1.47-5.43], p<0.01) and
      gastrointestinal hemorrhage (HR=1.68 [95%CI 1.01-2.78], p=0.04) were associated
      with OS in multivariate analysis. Only trunk PVT location was significantly
      associated with gastrointestinal hemorrhage in multivariate analysis (HR=5.56
      [95%CI 1.18-26.32], p=0.03). CONCLUSION: A high rate of variceal bleeding leading
      to death was found in this cohort. Endoscopic screening and the efficacy of
      prophylactic treatment of variceal bleeding remain to be evaluated in a
      prospective study.

PMID- 29183765
TI  - Developmental expression of anxiety and depressive behaviours after prenatal
      predator exposure and early life homecage enhancement.
AB  - Stressful events during gestation can have sex-specific effects on brain and
      behaviour, and may contribute to some of the differences observed in adult stress
      responding and psychopathology. We investigated the impact of a novel repeated
      prenatal psychological stress (prenatal predator exposure - PPS) during the last
      week of gestation in rats on offspring behaviours related to social interaction
      (play behaviour), open field test (OFT), forced swim test (FST) and sucrose
      preference test (SP) during the juvenile period and in adulthood. We further
      examined the role of postnatal environmental, using an enhanced housing condition
      (EHC), to prevent/rescue any changes. Some effects on anxiety, anhedonia, and
      stress-related coping behaviours (e.g., OFT, SP and OFT) did not emerge until
      adulthood. PPS increased OFT anxiety behaviours in adult males, and some OFT and
      SP behaviours in adult females. Contrary to this, EHC had few independent
      effects; most were apparent only when combined with PPS. In keeping with age
      group differences, juvenile behaviours did not necessarily predict the same adult
      behaviours although juvenile OFT rearing and freezing, and juvenile FST
      immobility did predict adult FST immobility and sucrose preference, suggesting
      that some aspects of depressive behaviours may emerge early and predict adult
      vulnerability or coping behaviours. Together, these results suggest an important,
      though complex, role for early life psychological stressors and early life
      behaviours in creating an adult vulnerability to anxiety or depressive disorders
      and that environmental factors further modulate the effects of the prenatal
      stressors.

PMID- 29183766
TI  - Ketogenic diet using a Japanese ketogenic milk for patients with epilepsy: A
      multi-institutional study.
AB  - BACKGROUND: In Japan, Meiji 817-B (M817-B), a powdered ketogenic milk, has been
      available since the ketogenic diet was introduced to infants and tube-fed
      children with medication-resistant epilepsy in the 1980s. METHODS: We
      retrospectively evaluated the efficacy, tolerability, and side effects of the
      ketogenic diet using M817-B as the main source of daily food intake for patients
      with epilepsy by sending questionnaires to the members of a subcommittee of the
      Japan Epilepsy Society that focuses on the proper use of M817-B. RESULTS: A total
      of 42 patients were enrolled. Age at the initiation of the diet therapy ranged
      from 3 to 244 months (median, 32.5 months). Thirty-four patients were fed via
      tube, and the remaining 8 were fed orally. About 93% of patients were able to
      continue the diet for 1 month, 74% for 3 months, and 64% for 6 months. The median
      period of continuation was 16 months. One patient was able to continue as long as
      7 years. The ketogenic ratio was maintained at about 3.0. The seizure-free rate
      and responder (>50% seizure reduction) rate were about 10% and 30-40%,
      respectively during the 12 months on the diet. Mean serum beta-hydroxybutyrate
      increased to almost 4 mM at 1 month and was maintained during the diet period.
      Side effects, which required discontinuation of the diet therapy, occurred in 11
      of 42 patients and included hypertonia, weight loss, vomiting, hypoglycemia,
      metabolic acidosis, and hypokalemia. CONCLUSION: M817-B could be used long-term
      with demonstrated efficacy in seizure reduction, although there are some side
      effects that may require cessation of the diet therapy.

PMID- 29183767
TI  - Diabetes induces mitochondrial dysfunction and alters cholesterol homeostasis and
      neurosteroidogenesis in the rat cerebral cortex.
AB  - The nervous system synthesizes and metabolizes steroids (i.e.,
      neurosteroidogenesis). Recent observations indicate that neurosteroidogenesis is
      affected by different nervous pathologies. Among these, long-term type 1
      diabetes, together with other functional and biochemical changes, has been shown
      to alter neuroactive steroid levels in the nervous system. Using an experimental
      model of type 1 diabetes (i.e., streptozotocin injection) we here show that the
      levels of these molecules are already decreased in the rat cerebral cortex after
      one month of the initiation of the pathology. Moreover, decreased levels of free
      cholesterol, together with alterations in the expression of molecules involved in
      cholesterol biosynthesis, bioavailability, trafficking and metabolism were
      detected in the rat cerebral cortex after one month of diabetes. Furthermore,
      mitochondrial functionality was also affected in the cerebral cortex and
      consequently may also contribute to the decrease in neuroactive steroid levels.
      Altogether, these results indicate that neurosteroidogenesis is an early target
      for the effect of type 1 diabetes in the cerebral cortex.

PMID- 29183768
TI  - Cardiovascular and renal interactions between cyclosporine and NSAIDs: Underlying
      mechanisms and clinical relevance.
AB  - Cyclosporine, the prototype calcineurin inhibitor, transformed immunosuppressant
      regimens and practices post-organ transplantation. Therapeutic uses of
      cyclosporine branched out to include management of different autoimmune
      disorders. However, multiple additional effects posed significant clinical
      challenges in face of the prolonged nature of cyclosporine use. Significantly,
      cyclosporine produced nephrotoxic, cardiotoxic and neurotoxic effects in addition
      to alteration of hemodynamic function. These adverse effects are shared with
      other drug groups further complicating the therapeutic situation to include
      potential exacerbation in case of drug interactions. The potential for
      detrimental outcomes increases with commonly used drugs such as non-steroidal
      anti-inflammatory drugs also notorious for their deleterious renal and
      cardiovascular effects. Herein, we review the available experimental and clinical
      evidence describing the mechanisms and the outcomes of interactions between the
      two drug classes. Special attention is given to the divergent toxic effects of co
      administration of cyclosporine with selective vs. non-selective cyclooxygenase
      inhibiting non-steroidal drugs.

PMID- 29183769
TI  - TPL2 kinase action and control of inflammation.
AB  - Tumor progression locus 2 (TPL2, also known as COT or MAP3K8) is a mitogen
      activated protein kinase kinase (MAP3K) activated downstream of TNFalphaR, IL1R,
      TLR, CD40, IL17R, and some GPCRs. TPL2 regulates the MEK1/2 and ERK1/2 pathways
      to regulate a cascade of inflammatory responses. In parallel to this, TPL2 also
      activates p38alpha and p38delta to drive the production of various inflammatory
      mediators in neutrophils. We discuss the implications of this finding in the
      context of various inflammatory diseases.

PMID- 29183770
TI  - Nutraceuticals: An emerging therapeutic approach against the pathogenesis of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is regarded as a progressive and devastating
      neurodegenerative disorder. In aged individuals, it is the most prevalent cause
      of dementia and is characterized by gradual loss of cognitive functions. In the
      last decade, numerous research works were undertaken to investigate the
      pathogenesis of AD. Although the etiology of AD is still not clear, several
      histopathological studies confirm prominent changes in the AD affected brains.
      The major changes include the formation of senile plaques and neurofibrillary
      tangles primarily owing to the deposition of amyloid beta plaques (Abeta) and
      hyper-phosphorylation of tau protein. Disruption of the redox homeostasis in the
      brain is a major triggering factor for the development of such pathophysiological
      conditions. Chemical formulations usually act by inhibiting activities of the
      enzymes responsible for the development of AD. But with time, these
      pharmacotherapies develop many side effects including toxicity in different
      organs. Recent researches are henceforth focused on the identification of novel
      therapeutic molecules from the nature's basket. This review aims to emphasize the
      therapeutic effects and regulation of molecular targets of different natural
      products such as curcumin, resveratrol, genistein and others. These prophylactic
      multipotent natural compounds have the potency to interfere with the formation as
      well as deposition of the Abeta peptides. These natural compounds have also been
      found in modulating different intracellular signalling molecules and enzymes
      including beta-secretase and gamma-secretase. This review article is expected to
      be helpful in understanding the recent progress in natural product research as a
      therapeutic approach in amelioration and/or delaying the detrimental effects of
      AD.

PMID- 29183771
TI  - Comparative study of Candida spp. isolates: Identification and echinocandin
      susceptibility in isolates obtained from blood cultures in 15 hospitals in
      Medellin, Colombia.
AB  - OBJECTIVES: Invasive candidiasis has a high impact on morbidity and mortality in
      hospitalised patients. Accurate and timely methods for identification of Candida
      spp. and determination of echinocandin susceptibility have become a priority for
      clinical microbiology laboratories. METHODS: This study was performed to compare
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      (MALDI-TOF/MS) identification with sequencing of the D1/D2 region of the rRNA
      gene complex 28 subunit in 147 Candida spp. isolates obtained from patients with
      candidaemia. Antimicrobial susceptibility testing was performed by broth
      microdilution (BMD) and Etest. Sequencing of the FKS1 and FKS2 genes was
      performed. RESULTS: The most common species isolated were Candida albicans
      (40.8%), followed by Candida parapsilosis (23.1%) and Candida tropicalis (17.0%).
      Overall agreement between the results of identification by MALDI-TOF/MS and
      molecular identification was 99.3%. Anidulafungin and caspofungin susceptibility
      by the BMD method was 98.0% and 88.4%, respectively. Susceptibility to
      anidulafungin and caspofungin by Etest was 93.9% and 98.6%, respectively.
      Categorical agreement between Etest and BMD was 91.8% for anidulafungin and 89.8%
      for caspofungin, with lower agreements in C. parapsilosis for anidulafungin
      (76.5%) and C. glabrata for caspofungin (40.0%). No mutations related to
      resistance were found in the FKS genes, although 54 isolates presented synonymous
      polymorphisms in the hotspots sequenced. CONCLUSIONS: MALDI-TOF/MS is a good
      alternative for routine identification of Candida spp. isolates. DNA sequencing
      of the FKS genes suggested that the isolates analysed were susceptible to
      echinocandins; alternatively, unknown resistance mechanisms or limitations
      related to antifungal susceptibility tests may explain the resistance found in a
      few isolates.

PMID- 29183772
TI  - Chinese Root-type Mustard Provides Phylogenomic Insights into the Evolution of
      the Multi-use Diversified Allopolyploid Brassica juncea.

PMID- 29183773
TI  - A Common Peptidolytic Mechanism for Targeting Peptide Degradation in Mitochondria
      and Chloroplasts.

PMID- 29183774
TI  - Accelerated subcutaneous immunotherapy in pediatric population - Systematic
      review.
AB  - BACKGROUND: Accelerated subcutaneous immunotherapy (SCIT) schedules represent an
      alternative to conventional SCIT, providing immunotherapy benefits in a shorter
      period of time. The objectives of this systematic review were to assess clinical
      and immunological efficacy as well as safety of accelerated SCIT build-up
      schedules for the treatment of respiratory allergy in pediatric patients.
      METHODS: Studies were located by searching PubMed, using "immunotherapy" and
      "desensitization" as keywords. The selection of studies, published from January
      1st, 2006, to December 31th, 2015, was performed in two stages: screening of
      titles and abstracts, and assessment of the full papers identified as relevant,
      considering the inclusion criteria. Data were extracted in a standardized way and
      synthesized qualitatively to assess efficacy and safety of accelerated schedules
      in respiratory allergy. RESULTS: Eleven trials were included: two evaluated rush
      SCIT and nine assessed cluster SCIT. This review demonstrated that rush and
      cluster schedules are clinically and immunological efficacious, with faster
      effect than conventional schedules. No relevant difference with respect to
      clinical outcomes was noticed between subgroups (pediatric, adult and mixed
      populations). Regarding safety, most local adverse reactions were mild and there
      were neither life-threatening systemic reactions nor fatal events. No relevant
      differences in the incidence and severity of either local or systemic reactions
      between the accelerated schedule group and control group were registered.
      CONCLUSIONS: Accelerated SCIT build-up schedules are effective in the treatment
      of respiratory allergy in pediatric patients, representing a safe alternative to
      the conventional schedules with the advantage of achieving clinical effectiveness
      sooner.

PMID- 29183775
TI  - Novel effects of phytoestrogenic soy isoflavones on serum calcium and chloride in
      premenopausal women: A 2-year double-blind, randomized, placebo-controlled study.
AB  - BACKGROUND: Soy phytoestrogens are potential alternatives to postmenopausal
      hormone replacement therapy (HRT). Adverse effects of HRT such as myocardial
      infarction, stroke, and pulmonary embolism are mediated by calcium-induced
      signaling. OBJECTIVE: To determine whether soy isoflavones affect serum calcium
      in healthy female subjects. DESIGN: In a double-blind trial, 197 premenopausal
      women were randomly assigned to either isoflavone (N = 99) or placebo pills (N =
      98) 5 days per week for up to 2 years, plus prenatal vitamins. Isoflavone pills
      contained 60 mg genistein, 60 mg daidzein and 16.6 mg glycitein (expressed as
      aglycone equivalents). All pills contained 15 mg riboflavin as an adherence
      marker. Blood chemistries and urinary daidzein, genistein and riboflavin were
      measured multiple times during the luteal phase before and during treatment.
      RESULTS: Analysis of the adherent population (N = 83 per group), revealed
      significantly strong associations between urinary levels of isoflavones and serum
      concentrations of calcium (regression coefficients 0.082 for daidzein and 0.229
      for genistein, all P < 0.01) and chloride (regression coefficient, -1.537 for
      genistein, P < 0.0001), mediated in part by albumin. The effects amounted to mean
      changes of +0.24 mg/dL for calcium and -1.45 mEq/L for chloride, with each visit
      for subjects excreting the most vs. the least amounts of isoflavones. These
      associations were not evident in the intention-to-treat analysis (N = 197) that
      did not assess expected variations in isoflavone levels within and between
      subjects from metabolism and adherence. CONCLUSIONS: These novel and strong
      effects of soy isoflavones on calcium homeostasis have important implications for
      long term effects of these natural substances on cardiovascular diseases.

PMID- 29183776
TI  - Assessment of microstructural signal compartments across the corpus callosum
      using multi-echo gradient recalled echo at 7 T.
AB  - Quantitative assessment of tissue microstructure is important in studying human
      brain diseases and disorders in which white matter is implicated, as it has been
      linked to demyelination, re-myelination, and axonal damage in clinical
      conditions. Ultra-high field magnetic resonance imaging data obtained using a
      multi-echo gradient echo sequence has been shown to contain information on
      myelin, axonal and extracellular compartments in white matter. In this study, we
      aimed to assess the sensitivity of a three-compartment model to estimate the
      variation of corresponding compartment parameters (water fraction, relaxation
      time and frequency shift) of the corpus callosum sub-regions, which are known to
      have different tissue structure. Additionally, we computed the g-ratio using
      myelin and axonal water fractions and performed a voxel-by-voxel analysis in the
      corpus callosum. Based on data acquired for ten participants, we show that the
      myelin compartment water fraction and T2* is consistent across the corpus
      callosum sub-regions, whilst myelin frequency shift varies. The results show that
      the variation in water fraction, T2* and frequency shift for the myelin signal
      compartment across the corpus callosum is smaller than for the axonal and
      extracellular signal compartments. The computed g-ratio was comparable to
      previously published studies in the corpus callosum. Our study suggests that a
      multi-echo GRE approach in vivo combined with a complex three-compartment model
      is sensitive to microstructural parameter variations across the human corpus
      callosum.

PMID- 29183777
TI  - Sensory and semantic activations evoked by action attributes of manipulable
      objects: Evidence from ERPs.
AB  - "Two route" theories of object-related action processing posit different temporal
      activation profiles of grasp-to-move actions (rapidly evoked based on object
      structure) versus skilled use actions (more slowly activated based on semantic
      knowledge). We capitalized on the exquisite temporal resolution and
      multidimensionality of Event-Related Potentials (ERPs) to directly test this
      hypothesis. Participants viewed manipulable objects (e.g., calculator) preceded
      by objects sharing either "grasp", "use", or no action attributes (e.g., bar of
      soap, keyboard, earring, respectively), as well as by action-unrelated but
      taxonomically-related objects (e.g., abacus); participants judged whether the two
      objects were related. The results showed more positive responses to "grasp-to
      move" primed objects than "skilled use" primed objects or unprimed objects
      starting in the P1 (0-150 ms) time window and continuing onto the subsequent N1
      and P2 components (150-300 ms), suggesting that only "grasp-to-move", but not
      "skilled use", actions may facilitate visual attention to object attributes.
      Furthermore, reliably reduced N400s (300-500 ms), an index of semantic
      processing, were observed to taxonomically primed and "skilled use" primed
      objects relative to unprimed objects, suggesting that "skilled use" action
      attributes are a component of distributed, multimodal semantic representations of
      objects. Together, our findings provide evidence supporting two-route theories by
      demonstrating that "grasp-to-move" and "skilled use" actions impact different
      aspects of object processing and highlight the relationship of "skilled use"
      information to other aspects of semantic memory.

PMID- 29183778
TI  - Current WHO guidelines and the critical role of immunohistochemical markers in
      the subclassification of non-small cell lung carcinoma (NSCLC): Moving from
      targeted therapy to immunotherapy.
AB  - Recent large scale genomic studies from the Clinical Lung Cancer Genome Project
      have identified different driver gene mutations in the subtypes of non-small cell
      lung carcinoma (NSCLC). These findings not only lead to remarkable progress in
      targeted therapies for lung cancer patients, but also provide fundamental
      knowledge for the subclassification of NSCLC. More recently, the advancement and
      clinical application of immunotherapy have reinforced the need for the accurate
      subclassification of NSCLC. In 2015, the World Health Organization (WHO) and the
      International Association for the Study of Lung Cancer (IASLC) updated their
      guidelines for the subclassification of lung cancers. These guidelines emphasize:
      (1) the subclassification of NSCLC, (2) the critical role of molecular
      characterization of tumors for targeted therapy, (3) the unique terminology for
      subclassifying NSCLC using small biopsy specimens, and (4) the utility of IHC
      biomarkers in the accurate diagnosis and subclassification of lung cancer. The
      guidelines have significant prognostic impact on oncologic practice and patient
      care. In this review, we summarize the current WHO guidelines for the
      classification of lung cancer, discuss advancements of targeted therapy and
      immunotherapy, and address the utility and limitation of immunomarkers in the
      subclassification of NSCLC, as well as the prospective future of the field.

PMID- 29183780
TI  - Effects of regular aerobic exercise on visual perceptual learning.
AB  - This study investigated the influence of five days of moderate intensity aerobic
      exercise on the acquisition and consolidation of visual perceptual learning using
      a motion direction discrimination (MDD) task. The timing of exercise relative to
      learning was manipulated by administering exercise either before or after
      perceptual training. Within a matched-subjects design, twenty-seven healthy
      participants (n = 9 per group) completed five consecutive days of perceptual
      training on a MDD task under one of three interventions: no exercise, exercise
      before the MDD task, or exercise after the MDD task. MDD task accuracy improved
      in all groups over the five-day period, but there was a trend for impaired
      learning when exercise was performed before visual perceptual training. MDD task
      accuracy (mean +/- SD) increased in exercise before by 4.5 +/- 6.5%; exercise
      after by 11.8 +/- 6.4%; and no exercise by 11.3 +/- 7.2%. All intervention groups
      displayed similar MDD threshold reductions for the trained and untrained motion
      axes after training. These findings suggest that moderate daily exercise does not
      enhance the rate of visual perceptual learning for an MDD task or the transfer of
      learning to an untrained motion axis. Furthermore, exercise performed immediately
      prior to a visual perceptual learning task may impair learning. Further research
      with larger groups is required in order to better understand these effects.

PMID- 29183779
TI  - Attention modulates trans-saccadic integration.
AB  - With every saccade, humans must reconcile the low resolution peripheral
      information available before a saccade, with the high resolution foveal
      information acquired after the saccade. While research has shown that we are able
      to integrate peripheral and foveal vision in a near-optimal manner, it is still
      unclear which mechanisms may underpin this important perceptual process. One
      potential mechanism that may moderate this integration process is visual
      attention. Pre-saccadic attention is a well documented phenomenon, whereby visual
      attention shifts to the location of an upcoming saccade before the saccade is
      executed. While it plays an important role in other peri-saccadic processes such
      as predictive remapping, the role of attention in the integration process is as
      yet unknown. This study aimed to determine whether the presentation of an
      attentional distractor during a saccade impaired trans-saccadic integration, and
      to measure the time-course of this impairment. Results showed that presenting an
      attentional distractor impaired integration performance both before saccade
      onset, and during the saccade, in selected subjects who showed integration in the
      absence of a distractor. This suggests that visual attention may be a mechanism
      that facilitates trans-saccadic integration.

PMID- 29183781
TI  - Evolution of Sucrose Metabolism: The Dichotomy of Invertases and Beyond.
AB  - In higher plants, invertases hydrolyze sucrose (Suc), the major end product of
      photosynthesis, into glucose (Glc) and fructose (Fru), which are used as
      nutrients, energy sources, and signaling molecules for plant growth, yield
      formation, and stress responses. The invertase enzymes, named CWINs, VINs, and
      CINs, are located in the cell wall, vacuole, and cytosol, respectively. We
      hypothesize, based on their distinctive subcellular locations and physiological
      roles, that invertases may have undergone different modes during evolution with
      important functional implications. Here, we provide phylogenetic and functional
      genomic evidence that CINs are evolutionarily and functionally more stable
      compared with CWINs and VINs, possibly reflecting their roles in maintaining
      cytosolic sugar homeostasis for cellular function, and that CWINs have coevolved
      with the vasculature, likely as a functional component of phloem unloading.

PMID- 29183782
TI  - Impact of dolutegravir and efavirenz on immune recovery markers: results from a
      randomized clinical trial.
AB  - OBJECTIVES: CD4/CD8 ratio and CD4+ T-cell percentage (CD4%) predicts the risk of
      AIDS and non-AIDS events. Multiple T-cell marker recovery (MTMR) has been
      proposed as the most complete level of immune reconstitution. We quantified
      differences in the CD4/CD8 ratio, CD4% recovery and MTMR after starting HIV-1
      treatment with dolutegravir/abacavir/lamivudine vs. efavirenz (EFV)/tenofovir
      (TDF)/emtricitabine (FTC). METHODS: Exploratory post hoc analysis of the SINGLE
      study, a randomized double-blind, clinical trial. Percentage differences and
      corresponding precision based on 95% confidence intervals, and p values were
      calculated for CD4/CD8 ratio normalization, CD4% normalization and the
      achievement of MTMR. Cox models taking into account competing risks were used to
      estimate sub-hazard ratios when comparing the times to normalization of the
      CD4/CD8 ratio and the CD4% by treatment arm. RESULTS: Data from 833 participants
      were analysed (414 in the dolutegravir/abacavir/lamivudine arm). There were no
      statistically significant differences in the proportion of patients who reached a
      CD4/CD8 ratio >=0.5 at weeks 48 and 96. However, at week 96, the proportion of
      patients with a CD4/CD8 ratio >=1 was higher in the EFV-TDF-FTC group
      (difference, 11.70; 95% confidence interval, 4.49-18.91; p 0.002). The decrease
      from baseline in CD8+ cell count was consistently greater in the EFV-TDF-FTC arm.
      Analysis of CD4+ percentages showed no significant differences during the study.
      The proportion of patients attaining a MTMR was higher in the EFV-TDF-FTC group,
      although the difference was only statistically significant at week 96 (p 0.001).
      CONCLUSIONS: EFV-TDF-FTC showed significantly greater increases in CD4/CD8 ratio
      >=1.0 or MTMR beyond treatment week 96. Additional studies are necessary to
      better understand the impact of these findings.

PMID- 29183783
TI  - Mesenchymal lineage cells and their importance in B lymphocyte niches.
AB  - Early B lymphopoiesis occurs in the bone marrow and is reliant on interactions
      with numerous cell types in the bone marrow microenvironment, particularly those
      of the mesenchymal lineage. Each cellular niche that supports the distinct stages
      of B lymphopoiesis is unique. Different cell types and signaling molecules are
      important for the progressive stages of B lymphocyte differentiation. Cells
      expressing CXCL12 and IL-7 have long been recognized as having essential roles in
      facilitating progression through stages of B lymphopoiesis. Recently, a number of
      other factors that extrinsically mediate B lymphopoiesis (positively or
      negatively) have been identified. In addition, the use of transgenic mouse models
      to delete specific genes in mesenchymal lineage cells has further contributed to
      our understanding of how B lymphopoiesis is regulated in the bone marrow. This
      review will cover the current understanding of B lymphocyte niches in the bone
      marrow and key extrinsic molecules and signaling pathways involved in these
      niches, with a focus on how mesenchymal lineage cells regulate B lymphopoiesis.

PMID- 29183784
TI  - Osteocalcin improves insulin resistance and inflammation in obese mice:
      Participation of white adipose tissue and bone.
AB  - AIMS/HYPOTHESIS: The discovery of osteocalcin, a protein synthetized by
      osteoblasts, as a hormone that has positive effects on insulin resistance,
      contributed to support the concept of bone as an endocrine organ. However, very
      little is known about the molecular pathways involved in osteocalcin improved
      insulin resistance. The present study aimed to investigate the mechanisms of
      action of osteocalcin on insulin resistance and inflammation in obese mice and
      3T3-L1 adipocytes. METHODS AND RESULTS: Lean control, saline-treated obese and
      uncarboxylated osteocalcin (uOC)-treated obese mice were subjected to insulin
      tolerance test in vivo. Blood was collect for biochemical/metabolic profile
      analysis; and, skeletal muscle, white adipose tissue (WAT) and bone were
      collected for protein (Western blotting) and mRNA (RT-qPCR) analysis. uOC effects
      on insulin resistance and inflammation were also investigated in 3T3-L1
      adipocytes challenged with tumor necrosis factor. Osteocalcin treatment improved
      in vivo insulin resistance in obese mice. In WAT, osteocalcin had positive
      effects such as (1) WAT weight reduction; (2) upregulation of glucose transporter
      (GLUT) 4 protein and its mRNA (Slc2a4); (3) improved insulin-induced AKT
      phosphorylation; (4) downregulation of several genes involved in inflammation and
      inflammassome transcriptional machinery, and (5) reduction of the density of
      macrophage in crown-like structures (histomorphometrical analysis). Notably, in
      3T3-L1 adipocytes, osteocalcin restored Slc2a4/GLUT4 content and reduced the
      expression of inflammatory genes after TNF-a challenge; moreover, osteocalcin
      treatment increased AKT phosphorylation induced by insulin. Finally, it was
      observed that in bone, osteocalcin improves insulin resistance by increasing
      insulin-induced AKT phosphorylation and reducing the expression of genes involved
      in bone insulin resistance, resulting in increased secretion of uncarboxylated
      osteocalcin in circulation. CONCLUSION: We provided some mechanisms of action for
      osteocalcin in the amelioration of insulin resistance in obesity: in WAT,
      osteocalcin improves insulin resistance by decreasing inflammation, and
      increasing insulin signaling and the expression of Slc2a4/GLUT4; and, in bone,
      osteocalcin increases the secretion of uncarboxylated osteocalcin by improving
      insulin resistance.

PMID- 29183785
TI  - Ablation of Gsalpha signaling in osteoclast progenitor cells adversely affects
      skeletal bone maintenance.
AB  - Gsalpha, the alpha stimulatory subunit of heterotrimeric G proteins that
      activates downstream signaling through the adenylyl cyclase and cAMP/PKA pathway,
      plays an important role in bone development and remodeling. The role of Gsalpha
      in mesenchymal stem cell (MSC) differentiation to osteoblasts has been
      demonstrated in several mouse models of Gsalpha inactivation. Previously, using
      mice with heterozygous germline deletion of Gsalpha (Gnas+/p-), we identified a
      novel additional role for Gsalpha in bone remodeling, and showed the importance
      of Gnas in maintaining bone quality by regulating osteoclast differentiation and
      function. In this study, we show that postnatal deletion of Gsalpha
      (CreERT2;Gnasfl/fl) leads to reduction in trabecular bone quality parameters and
      increased trabecular osteoclast numbers. Furthermore, mice with deletion of
      Gsalpha specifically in cells of the macrophage/osteoclast lineage (LysM
      Cre;Gnasfl/fl) showed reduced trabecular bone quality and increased trabecular
      osteoclasts, but to a reduced extent compared to the CreERT2;Gnasfl/fl global
      knockout. This demonstrates that while Gsalpha has a cell autonomous role in
      osteclasts in regulating bone quality, Gsalpha expression in other cell types
      additionally contribute. In both of these mouse models, cortical bone was more
      subtly affected than trabecular bone. Our results support that Gsalpha is
      required postnatally to maintain trabecular bone quality and that Gsalpha
      function to maintain trabecular bone is regulated in part through a specific
      activity in osteoclasts.

PMID- 29183786
TI  - Characterization of Protein Methyltransferases Rkm1, Rkm4, Efm4, Efm7, Set5 and
      Hmt1 Reveals Extensive Post-Translational Modification.
AB  - Protein methylation is one of the major post-translational modifications (PTMs)
      in the cell. In Saccharomyces cerevisiae, over 20 protein methyltransferases
      (MTases) and their respective substrates have been identified. However, the way
      in which these MTases are modified and potentially subject to regulation remains
      poorly understood. Here, we investigated six overexpressed S. cerevisiae protein
      MTases (Rkm1, Rkm4, Efm4, Efm7, Set5 and Hmt1) to identify PTMs of potential
      functional relevance. We identified 48 PTM sites across the six MTases, including
      phosphorylation, acetylation and methylation. Forty-two sites are novel. We
      contextualized the PTM sites in structural models of the MTases and revealed that
      many fell in catalytic pockets or enzyme-substrate interfaces. These may regulate
      MTase activity. Finally, we compared PTMs on Hmt1 with those on its human
      homologs PRMT1, PRMT3, CARM1, PRMT6 and PRMT8. This revealed that several PTMs
      are conserved from yeast to human, whereas others are only found in Hmt1. The
      mass spectrometry proteomics data have been deposited to the ProteomeXchange
      Consortium via the PRIDE partner repository with the dataset identifier
      PXD006767.

PMID- 29183787
TI  - Mechanism of Peptide Binding and Cleavage by the Human Mitochondrial Peptidase
      Neurolysin.
AB  - Proteolysis plays an important role in mitochondrial biogenesis, from the
      processing of newly imported precursor proteins to the degradation of
      mitochondrial targeting peptides. Disruption of peptide degradation activity in
      yeast, plant and mammalian mitochondria is known to have deleterious consequences
      for organism physiology, highlighting the important role of mitochondrial
      peptidases. In the present work, we show that the human mitochondrial peptidase
      neurolysin (hNLN) can degrade mitochondrial presequence peptides as well as other
      fragments up to 19 amino acids long. The crystal structure of hNLNE475Q in
      complex with the products of neurotensin cleavage at 2.7A revealed a closed
      conformation with an internal cavity that restricts substrate length and
      highlighted the mechanism of enzyme opening/closing that is necessary for
      substrate binding and catalytic activity. Analysis of peptide degradation in
      vitro showed that hNLN cooperates with presequence protease (PreP or PITRM1) in
      the degradation of long targeting peptides and amyloid-beta peptide, Abeta1-40,
      associated with Alzheimer disease, particularly cleaving the hydrophobic fragment
      Abeta35-40. These findings suggest that a network of proteases may be required
      for complete degradation of peptides localized in mitochondria.

PMID- 29183788
TI  - Reduction of Nonspecificity Motifs in Synthetic Antibody Libraries.
AB  - Successful antibody development requires both functional binding and desirable
      biophysical characteristics. In the current study, we analyze the causes of one
      hurdle to clinical development, off-target reactivity, or nonspecificity. We used
      a high-throughput nonspecificity assay to isolate panels of nonspecific
      antibodies from two synthetic single-chain variable fragment libraries expressed
      on the surface of yeast, identifying both individual amino acids and motifs
      within the complementarity-determining regions which contribute to the phenotype.
      We find enrichment of glycine, valine, and arginine as both individual amino
      acids and as a part of motifs, and additionally enrichment of motifs containing
      tryptophan. Insertion of any of these motifs into the complementarity-determining
      region H3 of a "clean" antibody increased its nonspecificity, with greatest
      increases in antibodies containing Trp or Val motifs. We next applied these rules
      to the creation of a synthetic diversity library based on natural frameworks with
      significantly decreased incorporation of such motifs and demonstrated its ability
      to isolate binders to a wide panel of antigens. This work both provides a greater
      understanding of the drivers of nonspecificity and provides design rules to
      increase efficiency in the isolation of antibodies with drug-like properties.

PMID- 29183789
TI  - A magnetic resonance imaging study of early brain injury in a rat model of acute
      DFP intoxication.
AB  - Current treatments for seizures induced by organophosphates do not protect
      sufficiently against progressive neurodegeneration or delayed cognitive
      impairment. Developing more effective therapeutic approaches has been challenging
      because the pathogenesis of these delayed consequences is poorly defined. Using
      magnetic resonance imaging (MRI), we previously reported brain lesions that
      persist for months in a rat model of acute intoxication with the OP,
      diisopropylfluorophosphate (DFP). However, the early spatiotemporal progression
      of these lesions remains unknown. To address this data gap, we used in vivo MRI
      to longitudinally monitor brain lesions during the first 3 d following acute DFP
      intoxication. Adult male Sprague Dawley rats acutely intoxicated with DFP
      (4mg/kg, sc) were MR imaged at 6, 12, 18, 24, 48, 72h post-DFP, and their brains
      then taken for correlative histology to assess neurodegeneration using FluoroJade
      C (FJC) staining. Acute DFP intoxication elicited moderate-to-severe seizure
      activity. T2-weighted (T2w) anatomic imaging revealed prominent lesions within
      the thalamus, piriform cortex, cerebral cortex, hippocampus, corpus striatum, and
      substantia nigra that corresponded to neurodegeneration, evident as bands of FJC
      positive cells. Semi-quantitative assessment of lesion severity demonstrated
      significant regional variation in the onset and progression of injury, and
      suggested that lesion severity may be modulated by isoflurane anesthesia. These
      results imply that the timing of therapeutic intervention for attenuating brain
      injury following OP intoxication may be regionally dependent, and that
      longitudinal assessment of OP-induced damage by MRI may be a powerful tool for
      assessing therapeutic response.

PMID- 29183790
TI  - 17beta-estradiol and tamoxifen protect mice from manganese-induced dopaminergic
      neurotoxicity.
AB  - Chronic exposure to manganese (Mn) causes neurotoxicity, referred to as
      manganism, with common clinical features of parkinsonism. 17beta-estradiol (E2)
      and tamoxifen (TX), a selective estrogen receptor modulator (SERM), afford
      neuroprotection in several neurological disorders, including Parkinson's disease
      (PD). In the present study, we tested if E2 and TX attenuate Mn-induced
      neurotoxicity in mice, assessing motor deficit and dopaminergic
      neurodegeneration. We implanted E2 and TX pellets in the back of the neck of
      ovariectomized C57BL/6 mice two weeks prior to a single injection of Mn into the
      striatum. One week later, we assessed locomotor activity and molecular mechanisms
      by immunohistochemistry, real-time quantitative PCR, western blot and enzymatic
      biochemical analyses. The results showed that both E2 and TX attenuated Mn
      induced motor deficits and reversed the Mn-induced loss of dopaminergic neurons
      in the substantia nigra. At the molecular level, E2 and TX reversed the Mn
      induced decrease of (1) glutamate aspartate transporter (GLAST) and glutamate
      transporter 1 (GLT-1) mRNA and protein levels; (2) transforming growth factor
      alpha (TGF-alpha) and estrogen receptor-alpha (ER-alpha) protein levels; and (3)
      catalase (CAT) activity and glutathione (GSH) levels, and Mn-increased (1)
      malondialdehyde (MDA) levels and (2) the Bax/Bcl-2 ratio. These results indicate
      that E2 and TX afford protection against Mn-induced neurotoxicity by reversing Mn
      reduced GLT1/GLAST as well as Mn-induced oxidative stress. Our findings may offer
      estrogenic agents as potential candidates for the development of therapeutics to
      treat Mn-induced neurotoxicity.

PMID- 29183791
TI  - Transforming growth factor beta 1 related gene polymorphisms in gestational
      hypertension and preeclampsia: A case-control candidate gene association study.
AB  - OBJECTIVES: To investigate the association between transforming growth factor
      beta 1 related gene polymorphisms and the occurrence of pregnancy induced
      hypertension, including gestational hypertension and preeclampsia. STUDY DESIGN:
      This is a case control candidate gene association study. A total of 130 patients
      with preeclampsia, 67 with gestational hypertension, and 316 controls were
      recruited. Eleven candidate SNPs of were examined, including four TGFbeta1 SNPs
      (rs1800469, rs4803455, rs4803457, and rs8179181), one TGFbetaR1 SNP (rs10739778),
      four TGFbetaR2 SNPs (rs1346907, rs3087465, rs6550005, and rs877572), and two ENG
      SNPs (rs10121110 and rs11792480). MAIN OUTCOME MEASURES: Logistic regression was
      used to estimate the OR and the 95% CI under different genetic models. Chi-square
      test was used to determine whether haplotype frequency distributions differed
      between the case and control groups and logistic regression was used to estimate
      ORs. To explore the associations between SNPs and blood pressure, SBP/DBP in
      different genotype groups in healthy women were compared by Wilcoxon rank sum
      test. RESULTS: We did not find significant association between investigated SNPs
      and pregnancy induced hypertension. The C-T-A-G haplotype of four TGFbetaR2 SNPs
      (rs877572, rs1346907, rs3087465, and rs6550005) was significantly associated with
      preeclampsia (OR = 4.71, 95%CI: 1.944, 11.409) and gestational hypertension (OR =
      3.157, 95%CI: 1.003, 9.938). The AA genotype of TGFbetaR1 rs10739778 was found to
      be associated with higher blood pressure in healthy women (p <= .008).
      CONCLUSIONS: Polymorphisms in TGFbetaR2 might participate in the pathologic
      process of pregnancy induced hypertension, and TGFbetaR1 rs10739778 was
      associated with blood pressure in our healthy participants.

PMID- 29183792
TI  - When two become one: Electrocortical correlates of the integration of multiple
      action consequences.
AB  - In a recent study we have demonstrated that the feedback-related negativity (FRN)
      reflects the integrated value of instantaneous and delayed decision consequences
      (Osinsky et al. 2017). In the present work, we extend this research by using a
      novel choice task in which instant and delayed consequence values of a single
      decision outcome can be manipulated independently of each other in a trial-wise
      manner. Fifty-nine healthy participants completed this task while EEG was
      recorded. Twenty-two of them returned one week later for a retesting, allowing
      for investigating temporal stability of individual FRN indices. Our results show
      that the FRN mainly reflects the additively integrated value of instant and
      delayed outcome consequences. Individual differences in the FRN sensitivity to
      the two consequence dimensions were specifically predictive for consequence
      driven adjustments in choice behavior and moderately stable over time.
      Altogether, our findings are inconsistent with the idea that the FRN reflects a
      simple binary distinction between favorable and unfavorable action outcomes.
      Rather, the FRN appears to mirror a fine-grained scaling of action outcomes,
      which results from stable personal reward preferences and which is used for
      adjusting choice behavior. Given that the FRN is generated in the anterior
      midcingulate cortex, our study adds to recent literature according to which this
      structure uses multiple information to learn complex action-outcome values.

PMID- 29183793
TI  - The electrocortical response to rewarding and aversive feedback: The reward
      positivity does not reflect salience in simple gambling tasks.
AB  - The Reward Positivity (RewP) is an event-related potential (ERP) potentiated to
      monetary gains and reduced to monetary losses. Recently, competing data suggest
      that more salient outcomes elicit a positivity relative to less salient outcomes,
      regardless of valence. However, all previous work testing the impact of salience
      on the RewP have examined expected versus unexpected outcomes. In the current
      study, participants completed the same gambling task twice in which feedback was
      equally probable: in one condition, feedback indicated monetary gain or loss-and
      in the other condition, feedback indicated either safety or punishment from
      subsequent electric shock. Traditional ERP and principal component analysis (PCA)
      derived measures confirmed that the RewP was more positive to feedback signaling
      monetary gain and safety from shock compared to feedback signaling monetary loss
      and punishment with shock. These results align with models in which the RewP
      indexes reward-related processes, including reward prediction error models.
      Potential explanations for salience-based effects on the RewP are discussed.

PMID- 29183794
TI  - Characterization of carp gonadotropins: Structure, annual profile, and carp and
      zebrafish pituitary topographic organization.
AB  - Two gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone
      (LH), are important players in the hypothalamic-pituitary-gonadal axis of
      vertebrates. In the present work, we describe the construction of recombinant (r)
      common carp (Cyprinus carpio; c) FSH (rcFSH) and LH (rcLH) using the Pichia
      pastoris system, the generation of specific antibodies against their respective
      beta subunits, and their use in the development and validation of specific
      ELISAs. We produced carp rLH and rFSH as single-chain polypeptides, wherein the
      GTH subunit alpha was joined with either cLHbeta or cFSHbeta mature protein
      coding sequences to form a fusion gene that encodes a yoked polypeptide, in which
      the GTH beta-subunit forms the N-terminal part and the alpha-subunit forms the C
      terminal part. Competitive ELISAs were developed, using primary antibodies
      against rcLHbeta or rcFSHbeta, respectively, and rcLHbetaalpha or rcFSHbetaalpha
      for the standard curves. The standard curves for cLH paralleled those of
      pituitary extracts of the homologous fish and also those of other cyprinids
      species like the black carp (Mylopharyngodon piceus), goldfish (Carassius
      auratus), silver carp (Hypophthalmichthys molitrix), and grass carp
      (Ctenopharyngodon idella). We used the specific antibodies raised against cFSH
      and cLH to study the specific localization of the different GTH cells in the
      pituitary of carp and its taxonomic relative species - the zebrafish. Both FSH
      and LH cells are localized in the center of the proximal pars distalis enveloping
      both sides of the neurohypophysis. LH cells form a continuous population
      throughout the PPD, while FSH cells are more loosely distributed throughout the
      same area and form small aggregations. Marked annual changes were encountered in
      gonadosomatic index (GSI), follicle diameter, mRNA levels and protein levels of
      FSH and LH. From September to November, all fish had low GSI, and the ovary
      contained previtellogenic follicles. From December, the GSI level increased and
      remained high until March, the follicular diameter reached its maximum in
      January, where the ovary contained large fully grown follicles. Thereafter,
      spawning occurred through March and April and ended in May, and GSI level and
      follicle diameter increased again; and the ovary contained mid-vitellogenic
      follicles. LH pituitary content and mRNA levels were low at pre- and early
      vitellogenesis, increasing gradually during this process to reach a peak of LH
      mRNA levels in mid vitellogenic ovary and a peak of LH content in fully grown
      ovarian follicles. However, no significant change occurred in FSH pituitary
      content and mRNA levels in vitellogenic fish and in fish during final maturation
      stages. A dramatic difference was found in the total content of each gonadotropin
      in the pituitary, with higher LH than FSH. Moreover, follicle diameter was
      positively and significantly correlated with LH pituitary content and its
      transcript levels - but not with the pituitary content or mRNA levels of FSH.
      Taken together, these results indicate that in carp, LH alone is sufficient to
      regulate both vitellogenesis and final oocyte maturation while FSH may have
      another, yet undefined role.

PMID- 29183795
TI  - From zebrafish to human: A comparative approach to elucidate the role of the
      thyroid hormone transporter MCT8 during brain development.
AB  - Monocarboxylate transporter 8 (MCT8) facilitates transmembrane transport of
      thyroid hormones (THs) ensuring their action on gene expression during vertebrate
      neurodevelopment. A loss of MCT8 in humans results in severe psychomotor deficits
      associated with the Allan-Herndon-Dudley Syndrome (AHDS). However, where and when
      exactly a lack of MCT8 causes the neurological manifestations remains unclear
      because of the varying expression pattern of MCT8 between specific brain regions
      and cells. Here, we elaborate on the animal models that have been generated to
      elucidate the mechanisms underlying MCT8-deficient brain development. The absence
      of a clear neurological phenotype in Mct8 knockout mice made it clear that a
      single species would not suffice. The evolutionary conservation of TH action on
      neurodevelopment as well as the components regulating TH signalling however
      offers the opportunity to answer different aspects of MCT8 function in brain
      development using different vertebrate species. Moreover, the plethora of tools
      for genome editing available today facilitates gene silencing in these animals as
      well. Studies in the recently generated mct8-deficient zebrafish and Mct8/Oatp1c1
      double knockout mice have put forward the current paradigm of impaired TH uptake
      at the level of the blood-brain barrier during peri- and postnatal development as
      being the main pathophysiological mechanism of AHDS. RNAi vector-based, cell
      specific induction of MCT8 knockdown in the chicken embryo points to an
      additional function of MCT8 at the level of the neural progenitors during early
      brain development. Future studies including also additional in vivo models like
      Xenopus or in vitro approaches such as induced pluripotent stem cells will
      continue to help unravelling the exact role of MCT8 in developmental events. In
      the end, this multispecies approach will lead to a unifying thesis regarding the
      cellular and molecular mechanisms responsible for the neurological phenotype in
      AHDS patients.

PMID- 29183796
TI  - Heat shock protein 70 suppresses neuroinflammation induced by alpha-synuclein in
      astrocytes.
AB  - Neuroinflammation triggered by activation of glial cells plays an important role
      in the pathophysiology of several neurodegenerative diseases including
      Parkinson's disease (PD). Besides microglia, astrocytes are also critical in
      initiating and perpetuating inflammatory process associated with PD. Heat shock
      protein 70 (Hsp70) is originally described as intracellular chaperone, however,
      recent study revealed that it had anti-inflammatory effects as well. The present
      study is designed to investigate whether Hsp70 mediates neuroinflammation in
      astrocytes. By employing alpha-synuclein (alpha-Syn) (A53T) aggregates on primary
      cultured astrocytes of rats, we found that astrocytes were activated and
      neuroinflammatory response was triggered, as indicated by over-expression of
      glial fibrillary acidic protein (GFAP), cyclooxygenase-2 (COX-2) and inducible
      nitric oxide synthase (iNOS), increased production of tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-1beta (IL-1beta). The data also showed that the
      neuroinflammatory response accompanied up-regulated Hsp70 expression. Moreover,
      over-expression of Hsp70 through transfection of Hsp70 cDNA plasmids could
      significantly reduce the production of TNF-alpha, IL-1beta, and the expression of
      GFAP, COX-2 as well as iNOS. While inhibition of Hsp70 by VER155008 exacerbated
      neuroinflammatory response in astrocytes challenged by alpha-Syn aggregates.
      Further mechanistic study indicated that c-Jun N-terminal kinase (JNK) and
      nuclear factor-kappaB (NF-kappaB) signalings were responsible for the
      neuroinflammation, which was also regulated by Hsp70. These findings demonstrated
      that Hsp70 was an important modulator in astrocytes induced inflammation, and up
      regulation of Hsp70 might be a potential regulating approach for
      neuroinflammation-related neurodegenerative diseases, such as PD.

PMID- 29183797
TI  - Increase in Ca2+ current by sustained cAMP levels enhances proliferation rate in
      GH3 cells.
AB  - AIMS: Ca2+ and cAMP are important intracellular modulators. In order to generate
      intracellular signals with various amplitudes, as well as different temporal and
      spatial properties, a tightly and precise control of these modulators in
      intracellular compartments is necessary. The aim of this study was to evaluate
      the effects of elevated and sustained cAMP levels on voltage-dependent Ca2+
      currents and proliferation in pituitary tumor GH3 cells. MAIN METHODS: Effect of
      long-term exposure to forskolin and dibutyryl-cyclic AMP (dbcAMP) on Ca2+ current
      density and cell proliferation rate were determined by using the whole-cell patch
      clamp technique and real time cell monitoring system. The cAMP levels were
      assayed, after exposing transfected GH3 cells with the EPAC-1 cAMP sensor to
      forskolin and dbcAMP, by FRET analysis. KEY FINDINGS: Sustained forskolin
      treatment (24 and 48h) induced a significant increase in total Ca2+ current
      density in GH3 cells. Accordingly, dibutyryl-cAMP incubation (dbcAMP) also
      elicited increase in Ca2+ current density. However, the maximum effect of dbcAMP
      occurred only after 72h incubation, whereas forskolin showed maximal effect at
      48h. FRET-experiments confirmed that the time-course to elevate intracellular
      cAMP was distinct between forskolin and dbcAMP. Mibefradil inhibited the fast
      inactivating current component selectively, indicating the recruitment of T-type
      Ca2+ channels. A significant increase on cell proliferation rate, which could be
      related to the elevated and sustained intracellular levels of cAMP was observed.
      SIGNIFICANCE: We conclude that maintaining high levels of intracellular cAMP will
      cause an increase in Ca2+ current density and this phenomenon impacts
      proliferation rate in GH3 cells.

PMID- 29183798
TI  - Altered membrane integrity in the progression of muscle diseases.
AB  - Sarcolemmal integrity is orchestrated through the interplay of preserving
      membrane strength and fast tracking the membrane repair process during an event
      of compromised membrane fragility. Several molecular players have been identified
      that act in a concerted fashion to maintain the barrier function of the muscle
      membrane. Substantial research findings in the field of muscle biology point out
      the importance of maintaining membrane integrity as a key contributory factor to
      cellular homeostasis. Innumerable data on the progression of membrane pathology
      associated with compromised muscle membrane integrity support targeting
      sarcolemmal integrity in skeletal and cardiac muscle as a model therapeutic
      strategy to alleviate some of the pathologic conditions. This review will discuss
      strategies that researchers have undertaken to compensate for an imbalance in
      sarcolemma membrane fragility and membrane repair to maintain muscle membrane
      integrity.

PMID- 29183799
TI  - Is testicular dysgenesis syndrome a genetic, endocrine, or environmental disease,
      or an unexplained reproductive disorder?
AB  - Progressive increases in the incidence of male reproductive disorders inclusive
      of hypospadias, cryptorchidism, poor semen quality, and testicular germ cell
      cancer (TGCC) have been observed in recent times. The central hypothesis of this
      study asserted that these disorders may all collectively signify testicular
      dysgenesis syndrome (TDS). This review aimed to provide evidence verifying the
      reality of TDS based on four key aspects: environmental endocrine-disrupting
      chemicals (EDCs), genetic factors, intrauterine growth disorders and lifestyle
      factors. Although TDS might result from genetic polymorphisms or aberration,
      recent evidence has highlighted links indicating the conditions associations to
      both environmental and lifestyle factors due to the rapid temporal changes in the
      clinical symptoms observed over recent decades. Based on our review of genetic
      and environmental factors, a key observation of our study suggested that there is
      an urgent need to prioritize research in reproductive physiology and
      pathophysiology, particularly in highly industrialized countries facing
      decreasing populations. At present, current research has yet to elucidate the
      mechanisms of TDS, in addition to the lack of genuine consideration of a variety
      of potentially key factors and TDS mechanisms. In conclusion, our study revealed
      that environmental exposures owing to modern lifestyles are primary factors
      involved in the associated trends of the syndrome, which are capable of affecting
      the adult endocrine system via direct means or through epigenetic mechanisms.

PMID- 29183800
TI  - Formulations based on solid lipid nanoparticles (SLN) and nanostructured lipid
      carriers (NLC) for cutaneous use: A review.
AB  - Cutaneous use of lipid nanoparticles (solid lipid nanoparticles, SLN and
      nanostructured lipid carriers, NLC) has been showing promising results. These
      systems consist of low viscosity aqueous dispersions, being usually employed by
      means of semi-solid formulations with adequate consistency for skin application.
      This review addresses the cutaneous use of lipid nanoparticles for therapeutic
      and cosmetic applications. Initially, general information related to
      pharmaceutical semi-solid formulations is presented. Afterwards, the effects of
      SLN and NLC on the skin, and technological aspects related to semi-solid systems
      based on SLN or NLC are described. Finally, the most relevant studies related to
      the formulations based on SLN and NLC, for cosmetic and therapeutic applications,
      are reported. Notwithstanding the cutaneous use of SLN and NLC has been proposed
      for both local and transdermal delivery, the reported studies show promising
      results only for local application. In this sense, more research is required to
      better understanding the interaction mechanisms of lipid nanoparticles with skin
      lipids. Furthermore, the development of standard methods for skin experiments
      with nanoparticles is necessary.

PMID- 29183801
TI  - Cryptococcus neoformans peritonitis in the cirrhotic patient.

PMID- 29183802
TI  - Zika virus: An emerging player in the global scenario.

PMID- 29183803
TI  - 8-Nitro-cGMP is a promoter of osteoclast differentiation induced by RANKL.
AB  - Osteoclasts are multinucleated giant cells differentiated from monocyte
      macrophage-lineage cells under stimulation of receptor activator of nuclear
      factor kappa-B (RANK) ligand (RANKL) produced by osteoblasts and osteocytes.
      Although it has been reported that nitric oxide (NO) and reactive oxygen species
      (ROS) are involved in this process, the mechanism by which these labile molecules
      promote osteoclast differentiation are not fully understood. In this study, we
      investigated the formation and function of 8-nitro-cGMP, a downstream molecule of
      NO and ROS, in the process of osteoclast differentiation in vitro. 8-Nitro-cGMP
      was detected in mouse bone marrow macrophages and osteoclasts differentiated from
      macrophages in the presence of RANKL. Inhibition of NO synthase suppressed the
      formation of 8-nitro-cGMP as well as RANKL-induced osteoclast differentiation
      from macrophages. On the other hand, RANKL-induced osteoclast differentiation was
      promoted by addition of 8-nitro-cGMP to the cultures. In addition, 8-nitro-cGMP
      enhanced the mRNA expression of RANK, the receptor for RANKL. However, 8-bromo
      cGMP, a membrane-permeable derivative of cGMP, did not have an effect on either
      RANKL-induced osteoclast differentiation or expression of the RANK gene. These
      results suggest that 8-nitro-cGMP is a novel positive regulator of osteoclast
      differentiation, which might help to explain the roles of NO and ROS in
      osteoclast differentiation.

PMID- 29183804
TI  - Modulation of nNOSser852 phosphorylation and translocation by PKA/PP1 pathway in
      endothelial cells.
AB  - Neuronal nitric oxide synthase (nNOS) is now considered an important player in
      vascular function. It has a protective role in atherosclerosis and hypertension.
      However, despite its importance, little is known about the mechanisms that
      regulate its activity in vascular cells. Here we explore the mechanisms by which
      nNOS is activated in endothelium. We evaluated aorta relaxation response and
      phosphorylation of nNOS during protein phosphatases 1 and 2 (PP1 and PP2)
      inhibition, in eNOS silenced mice. PP1 translocation and interaction between the
      nuclear inhibitor of PP1 (NIPP1) and PP1 was evaluated in endothelial EA.hy926
      cells. We demonstrate here that acetylcholine (Ach)-induced relaxation is
      completely abolished by nNOS inhibition in eNOS silenced mice aorta which also
      decreased NO and H2O2 concentrations. ACh induced dephosphorylation of nNOSser852
      in aorta after 20 min stimulation. Endothelial cells also showed a decrease in
      nNOSser852 phosphorylation during 20 min of ACh stimulation. PP2 inhibition had
      no effect on Ach-induced nNOSSer852 dephosphorylation in endothelial cells and
      did not modify Ach-induced vasodilation in aorta from eNOS silenced mice. Non
      selective PP1/PP2 inhibition prevented nNOSSer852 dephosphorylation in
      endothelial cells and prevented Ach-induced vasodilation in eNOS silenced mice.
      ACh induced time-dependent PP1 and NIPP1 dissociation and PP1 translocation to
      cytoplasm. Protein kinase A (PKA) inhibition abolished PP1 translocation and
      further nNOSser852 dephosphorylation. In addition, 8-Br-cAMP reduced NIPP1/PP1
      interaction, stimulated PP1 translocation and nNOSser852 dephosphorylation.
      Moreover, PKA Inhibition led to a decreased nNOS translocation to perinuclear
      region. Taken together, our results elucidate a mechanism whereby PP1 is
      activated by a cAMP/PKA-dependent pathway, leading to dephosphorylation of
      nNOSser852 and subsequent NO and possible H2O2 production resulting in
      endothelium-dependent vascular relaxation.

PMID- 29183805
TI  - Proteome profiles of different types of thyroid cancers.
AB  - Proteomics profiling of tissue specimens representative for major types of
      thyroid cancers: papillary (classical and follicular variant), follicular,
      anaplastic and medullary, as well as benign follicular adenoma, was performed
      using shotgun LC-MS/MS approaches. A combination of Orbitrap and MALDI-TOF
      approach allowed to identify protein products of 3700 unique genes and revealed
      large differences between medullary, anaplastic and epithelium-derived
      differentiated cancers (papillary and follicular). Proteins characteristic for
      medullary and anaplastic cancers included factors associated with neuroendocrine
      functions and factors typically associated with advanced malignancies,
      respectively. Proteomes of different types of epithelium-derived differentiated
      cancers and follicular adenoma were compared using multi-enzyme LC-MS/MS
      approach, which revealed products of 4800 unique genes. A comparable overall
      similarity of follicular cancers to both variants of papillary cancers was found.
      Moreover, follicular adenoma showed higher overall similarity to follicular
      cancer than to either variant of papillary cancer. Proteins discriminating
      differentiated thyroid neoplasms included factors associated with lipid and
      hormone metabolism, regulation of gene expression and maintenance of DNA
      structure. Importantly, proteome data matched several features of transcriptome
      and metabolome profiles of thyroid cancers contributing to systems biology of
      this malignancy.

PMID- 29183806
TI  - The antagonist properties of Bazedoxifene after acute treatment are shifted to
      stimulatory action after chronic exposure in the liver but not in the uterus.
AB  - A promising alternative to conventional hormone therapy for postmenopausal
      symptoms is treatment combining Bazedoxifene (BZA), a third-generation selective
      estrogen receptor modulator (SERM), and conjugated equine estrogen (CE). This
      combination is also known as a tissue-selective estrogen complex (TSEC).
      Understanding the tissue-specific actions of SERMs and the TSEC remains a major
      challenge to try to predict their clinical effects. The aim of this study was to
      compare acute versus chronic treatment with BZA, CE or CE + BZA in two major
      targets of estrogens, the uterus and the liver. In these two tissues, acute
      treatment with CE, but not with BZA, induced similar gene expression change than
      the most important endogenous estrogen, 17-beta estradiol (E2). Acute induction
      of gene expression by E2 or by CE was antagonized by the addition of BZA.
      Concomitantly, BZA alone or in combination with E2 or CE induced a partial
      degradation of ERalpha protein after acute exposure. In uterus, chronic treatment
      of BZA alone had no impact on tissue weight gain or on epithelial cell
      proliferation, and also antagonized CE-effect in uterus, thereby mimicking the
      acute effect. By contrast, in the liver, chronic BZA and CE + BZA elicited
      agonistic transcriptional effects similar to those of CE alone. In addition, at
      variance to BZA acute effect, no change in ERalpha protein abundance was observed
      after chronic treatment in this tissue. These experimental in vivo data highlight
      a new aspect of the time-dependent tissue-specific action of BZA or TSEC, i.e.
      they can act acutely as antagonists but become agonists after chronic treatment.
      This shift was observed in liver tissue, but not in proliferative sex target such
      as the uterus.

PMID- 29183807
TI  - Neonatal overfeeding increases capacity for catecholamine biosynthesis from the
      adrenal gland acutely and long-term in the male rat.
AB  - A poor nutritional environment during early development has long been known to
      increase disease susceptibility later in life. We have previously shown that rats
      that are overfed as neonates (i.e. suckled in small litters (4 pups) relative to
      control conditions (12 pups)) show dysregulated hypothalamic-pituitary-adrenal
      axis responses to immune stress in adulthood, particularly due to an altered
      capacity of the adrenal to respond to an immune challenge. Here we hypothesised
      that neonatal overfeeding similarly affects the sympathomedullary system, testing
      this by investigating the biochemical function of tyrosine hydroxylase (TH), the
      first rate-limiting enzyme in the catecholamine synthesis. We also examined
      changes in adrenal expression of the leptin receptor and in mitogen-activated
      protein kinase (MAPK) signalling. During the neonatal period, we saw age
      dependent changes in TH activity and phosphorylation, with neonatal overfeeding
      stimulating increased adrenal TH specific activity at postnatal days 7 and 14,
      along with a compensatory reduction in total TH protein levels. This increased TH
      activity was maintained into adulthood where neonatally overfed rats exhibited
      increased adrenal responsiveness 30 min after an immune challenge with
      lipopolysaccharide, evident in a concomitant increase in TH protein levels and
      specific activity. Neonatal overfeeding significantly reduced the expression of
      the leptin receptor in neonatal adrenals at postnatal day 7 and in adult
      adrenals, but did not affect MAPK signalling. These data suggest neonatal
      overfeeding alters the capacity of the adrenal to synthesise catecholamines, both
      acutely and long term, and these effects may be independent of leptin signalling.

PMID- 29183808
TI  - The vitamin D receptor (VDR) binds to the nuclear matrix via its hinge domain: A
      potential mechanism for the reduction in VDR mediated transcription in mitotic
      cells.
AB  - Vitamin D is best known for its regulation of calcium homeostasis. Vitamin D
      exerts its genomic actions via the vitamin D receptor (VDR). As a member of the
      superfamily of nuclear receptors (NR), the VDR is primarily located within the
      nucleus of non-dividing cells. We show here that the VDR relocates from the
      nucleus into the cytoplasm across all stages of cell division in CHO cells.
      Furthermore, we show that the VDR is transcriptionally inert during cell
      division. In addition, 1alpha, 25 dihydroxyvitamin D (1,25(OH)2D3) promotes VDR
      binding to the nuclear matrix. Finally, we assessed the structural nature of VDR
      binding to the nuclear matrix. Mutation of the hinge domain reduced VDR's ability
      to bind to the nuclear matrix and to initiate transcription in response to
      1,25(OH)2D3. Taken together, our data suggest that the association between the
      VDR and the nuclear matrix accounts for the apparent cytosolic distribution as
      the matrix disperses within the cytoplasm when cells divide. This may also
      explain the dramatic reduction in VDR mediated transcription during cell
      division. Our data also confirm that similar to other NRs, the hinge domain of
      the VDR is responsible for this association.

PMID- 29183809
TI  - The effects of high glucose exposure on global gene expression and DNA
      methylation in human pancreatic islets.
AB  - BACKGROUND: Type 2 diabetes (T2D) is a complex disease characterised by chronic
      hyperglycaemia. The effects of elevated glucose on global gene expression in
      combination with DNA methylation patterns have not yet been studied in human
      pancreatic islets. Our aim was to study the impact of 48 h exposure to high (19
      mM) versus control (5.6 mM) glucose levels on glucose-stimulated insulin
      secretion, gene expression and DNA methylation in human pancreatic islets.
      RESULTS: While islets kept at 5.6 mM glucose secreted significantly more insulin
      in response to short term glucose-stimulation (p = 0.0067), islets exposed to
      high glucose for 48 h were desensitised and unresponsive to short term glucose
      stimulation with respect to insulin secretion (p = 0.32). Moreover, the exposure
      of human islets to 19 mM glucose resulted in significantly altered expression of
      eight genes (FDR<5%), with five of these (GLRA1, RASD1, VAC14, SLCO5A1, CHRNA5)
      also exhibiting changes in DNA methylation (p < 0.05). A gene set enrichment
      analysis of the expression data showed significant enrichment of e.g. TGF-beta
      signalling pathway, Notch signalling pathway and SNARE interactions in vesicular
      transport; these pathways are of relevance for islet function and possibly also
      diabetes. We also found increased DNA methylation of CpG sites annotated to PDX1
      in human islets exposed to 19 mM glucose for 48 h. Finally, we could functionally
      validate a role for Glra1 in insulin secretion. CONCLUSION: Our data demonstrate
      that high glucose levels affect human pancreatic islet gene expression and
      several of these genes also exhibit epigenetic changes. This might contribute to
      the impaired insulin secretion seen in T2D.

PMID- 29183810
TI  - Identification, structural characterization, and expression analysis of toll-like
      receptors 2 and 3 from gibel carp (Carassius auratus gibelio).
AB  - Toll-like receptors (TLRs) are important components of innate immunity. TLRs
      recognize pathogen-associated molecular patterns (PAMPs) and initiate downstream
      signaling pathways in response. In present study, we report the identification of
      two TLRs from gibel carp (Carassius auratus gibelio), TLR2 and TLR3 (designated
      CagTLR2 and CagTLR3, respectively). We report on the genomic structures and mRNA
      expression patterns of CagTLR2 and CagTLR3. Five exons and four introns were
      identified from the genomic DNA sequence of CagTLR3 (4749 bp in total length);
      this genomic organization is similar to that of TLR3 in zebrafish and human.
      However, only one intron was identified from the CagTLR2 genomic locus (3166 bp
      in total length); this unique genomic organization of CagTLR2 is different from
      that of TLR2 in fish and humans. The cDNAs of CagTLR2 and CagTLR3 encoded 791 and
      904 amino acid residues, respectively. CagTLR2 and CagTLR3 contained two distinct
      structural/functional motifs of the TLR family: a leucine-rich repeat (LRR)
      domain in the extracellular portion and a toll/interleukin-1 receptor (TIR)
      domain in the intracellular portion. The positions of critical amino acid
      residues involed in PAMP recognition and signaling pathway transduction in
      mammalian TLRs were conserved in CagTLR2 and CagTLR3. Phylogenetic analysis
      revealed a closer clustering of CagTLR2 and CagTLR3 with TLRs from freshwater
      fish than with marine fish species. In healthy gibel carp, transcripts of these
      genes were detected in all examined tissues, and high expression levels of
      CagTLR2 and CagTLR3 were observed in liver and brain, respectively. Following
      injection with CyHV-2, expression levels of CagTLR2 and CagTLR3 were
      significantly upregulated in the spleens of gibel carp after three days, and
      CagTLR3 transcript levels were rapidly increased in head kidney after 12 h. These
      results suggest that CagTLR2 and CagTLR3 are functionally involved in the
      induction of antiviral immune response.

PMID- 29183811
TI  - TO17: A teleost antimicrobial peptide that induces degradation of bacterial
      nucleic acids and inhibits bacterial infection in red drum, Sciaenops ocellatus.
AB  - Tissue factor pathway inhibitor (TFPI)-1 is well known for its role as an
      inhibitor of blood coagulation. Several studies have demonstrated that the C
      terminal peptides of TFPI-1 are active against a broad spectrum of
      microorganisms. In a previous study, we found that TO17 (with 17 amino acids), a
      TFPI-1 C-terminal peptide from red drum (Sciaenops ocellatus), was active against
      Edwardsiella tarda. In the present study, we investigated further the
      antimicrobial spectrum, action mode, as well as the immunostimulatory property of
      TO17. Our results showed that TO17 displayed antimicrobial activity against
      Staphylococcus aureus, Micrococcus luteus, Vibrio vulnificus, and infectious
      spleen and kidney necrosis virus, independent of host serum. Furthermore, the
      activity of TO17 was influenced by the length or type of amino acids at the N and
      C termini. During its interaction with V. vulnificus, TO17 exerted its
      antibacterial activity by destroying cell membrane integrity, penetrating the
      cytoplasm and inducing degradation of genomic DNA and total RNA. In addition,
      TO17 had no hemolytic activity against red drum blood cells. In vitro, TO17
      enhanced production of nitric oxide and bactericidal activity of red drum
      macrophages. In vivo, administration of red drum with TO17 before bacterial
      infection significantly reduced pathogen dissemination and replication in
      tissues. These results indicate that TO17 is a broad-spectrum antimicrobial
      peptide with immunostimulatory properties and it has the potential to be used as
      an antimicrobial agent in aquaculture.

PMID- 29183812
TI  - Muli bamboo (Melocanna baccifera) leaves ethanolic extract a non-toxic phyto
      prophylactic against low pH stress and saprolegniasis in Labeo rohita
      fingerlings.
AB  - Bamboo (Melocanna baccifera) plant plays a significant role in traditional Asian
      medicine and it can be used as an alternative to various chemo-therapeutics or
      prophylactic agents used in aquaculture. In the present study, the 1st experiment
      was done for the preparation of extracts from bamboo leaves by using 90% alcohol
      as a solvent. In the 2nd experiment, toxicity study was carried on Labeo rohita
      fingerlings (average length of 10.3 +/- 1.5 cm and weight 18.5 +/- 1.5 g) using
      BLAL (Bamboo Leaf Alcoholic) extract and it did not show any mortalities in fish
      even at the dose of 20 g kg-1 body weight, which can be regarded as virtually non
      toxic with minimal effect. The 3rd experiment was conducted to find out the
      effect of BLAL extract based isocaloric and isonitrogenous feed (doses: control-
      0.0%, diet T1-0.01%, diet T2-0.1%, diet T3-1% BLAL extract kg-1 feed) on the
      haemato-immuno-biochemical parameters of L. rohita fingerlings (average length
      15.7 +/- 1.5 cm and weight 20.2 +/- 1.5 g). Regular sampling was done (on 7th,
      15th, 30th and 60th day of feeding) for different haematological, immunological
      and biochemical parameters. The study revealed that the best response occurred
      within 7 days of feeding with BLAL extract and long-term feeding have shown
      immunosuppressive condition in the fish. In the 4th experiment, fish were exposed
      to multiple stressors like low pH stress, and Saprolegnia parastica infection
      after feeding with BLAL extract (0.1%) based feed for 7 days. The study showed
      that the BLAL extract can make fish resistant to single stress however, not able
      to reduce the fish mortality under multiple stresses (S. parastica infection
      under low pH). Thus, it can be concluded that the BLAL has the potentiality to be
      used as a non-toxic phyto-prophylactic which can induce non-specific immune
      response, reduces the low pH stress responses and increases the resistance
      against saprolegniasis under neutral pH condition in rohu fingerlings.

PMID- 29183813
TI  - Reduced glutathione supplementation in practical diet improves the growth, anti
      oxidative capacity, disease resistance and gut morphology of shrimp Litopenaeus
      vannamei.
AB  - The present study was conducted to investigate the effects of reduced glutathione
      (GSH) supplementation in practical diet on growth performance, anti-oxidative
      response, disease resistance and intestine morphology of shrimp Litopenaeus
      vannamei. Two control diets based on the commercial formulation were designed
      with high level (27%) and low level (22%) of fish meal, respectively. Based on
      the control diet with low level of fish meal, 75, 150 and 225 mg/kg of GSH were
      added, respectively, to make the other three experimental diets. The five
      formulated diets were named as C1, C2, G1, G2 and G3, respectively. The shrimp
      (initial body weight: 0.30 +/- 0.02 g) were fed with the five experimental diets
      for 8 weeks followed by a challenge test with Vibrio parahaemolyticus. The
      results showed that the specific growth rate (SGR) of shrimp in the C2 group was
      significantly lower than that in C1. The SGRs in G1 and G2 had no significant
      difference with those in C1 and C2. However, the SGR in G3 was significantly
      lower than that in C1. The serum GSH concentration in C2 was significantly lower
      than the other groups, but the malondialdehyde concentration was significantly
      higher. The supplementation of dietary GSH significantly improved the total anti
      oxidative capacity and activities of glutathione S-transferase and glutathione
      peroxidase in serum. The villus height of intestine in the GSH supplemented
      groups had no significant difference with C1, but was significantly higher than
      C2. The jejunum wall thickness of intestine in G2 and G3 was significantly higher
      than those in the other groups. After the challenge test, the cumulative
      mortalities in G1 and G2 were significantly lower than C1 and C2. However, there
      was no significant difference in cumulative mortalities among G3, C1 and C2. In
      conclusion, based on the present experimental conditions, 75-150 mg/kg of GSH was
      suggested to be supplemented into the practical diet to improve the growth, anti
      oxidative capacity, disease resistance and gut health of shrimp L. vannamei.

PMID- 29183815
TI  - Bioscavenger is effective as a delayed therapeutic intervention following
      percutaneous VX poisoning in the guinea-pig.
AB  - The prolonged systemic exposure that follows skin contamination with low
      volatility nerve agents, such as VX, requires treatment to be given over a long
      time due to the relatively short half-lives of the therapeutic compounds used.
      Bioscavengers, such as butyrylcholinesterase (BChE), have been shown to provide
      effective post-exposure protection against percutaneous nerve agent when given
      immediately on signs of poisoning and to reduce reliance on additional
      treatments. In order to assess the benefits of administration of bioscavenger at
      later times, its effectiveness was assessed when administration was delayed for
      2h after the appearance of signs of poisoning in guinea-pigs challenged with VX
      (4*LD50). VX-challenged animals received atropine, HI-6 and avizafone on signs of
      poisoning and 2h later the same combination with or without bioscavenger. Five
      out of 6 animals which received BChE 2h after the appearance of signs of
      poisoning survived to the end of the study at 48h, compared with 6 out of 6 which
      received BChE immediately on signs. All the animals (n=6+6) that received only
      MedCM, without the addition of BChE, died within 10h of poisoning. The
      toxicokinetics of a sub-lethal challenge of percutaneous VX were determined in
      untreated animals. Blood VX concentration peaked at approximately 4h after
      percutaneous dosing with 0.4*LD50; VX was still detectable at 36h and had
      declined to levels below the lower limit of quantification (10pg/mL) by 48h in 7
      of 8 animals, with the remaining animal having a concentration of 12pg/mL. These
      studies confirm the persistent systemic exposure to nerve agent following
      percutaneous poisoning and demonstrate that bioscavenger can be an effective
      component of treatment even if its administration is delayed.

PMID- 29183814
TI  - Sulfur mustard resistant keratinocytes obtained elevated glutathione levels and
      other changes in the antioxidative defense mechanism.
AB  - BACKGROUND: Sulfur mustard (SM) is a potent blistering chemical warfare agent,
      which was first used in 1917. Despite the Chemical Weapons Convention, a use was
      recently reported in Syria in 2015. This emphasizes the importance to develop
      countermeasures against chemical warfare agents. Despite intensive research,
      there is still no antidote or prophylaxis available against SM. METHODS: The
      newly developed SM-resistant keratinocyte cell line HaCaT/SM was used to identify
      new target structures for drug development, particularly the adaptations in
      protective measures against oxidative stress. For this purpose, glutathione (GSH)
      and NAD(P)H levels, the effect of glutathione S-transferase (GST) inhibition as
      well as activation and expression of Nrf2, GST, glutamate cysteine ligase (GCL)
      and glutathione-disulfide reductase (GSR) as well as multi-drug resistance (MDR)
      proteins 1, 3 and 5 were investigated. RESULTS: The HaCaT/SM cells showed not
      only a better survival after treatment with SM or cytostatic drugs, but also
      hydrogen peroxide (H2O2). They exhibit more GSH even after SM treatment. Nrf2
      levels were significantly lower. Inhibition of GST led to significantly
      decreased, activation to slightly higher IC50 values after SM treatment and a
      lower expression of GST was observed. The cells also expressed less GCLC and GSR.
      Expression of MDR1, MDR3 and MDR5 was higher under control conditions, but less
      stimulated by SM treatment. An increased NADP+/NADPH ratio as well as higher NAD+
      levels were shown. CONCLUSION: In summary, an improved response of the resistant
      cell line to oxidative stress was observed. The underlying mechanisms are
      elevated GSH levels as well as lower expression of Nrf2 and its targets GCLC and
      GST as well as GSR and MDR1, MDR3 and MDR5. GST is an especially interesting
      target because its inhibition already induced a significant SM sensitivity. SM
      resistance also caused redox equivalent level differences. Taken together, these
      findings provide further insight into the mechanism of SM resistance and may open
      a window for novel therapeutic targets in SM therapy.

PMID- 29183816
TI  - Evaluation of diffusion weighted imaging in the context of multi-parametric MRI
      of the prostate in the assessment of suspected low volume prostatic carcinoma.
AB  - Data from a multi-parametric MRI study of patients with possible early-stage
      prostate cancer was assessed with a view to creating a more efficient clinical
      protocol. Based on a correlation analysis suggesting that diffusion-weighted
      imaging (DWI) scores are more strongly correlated with overall PIRADS scores than
      other modalities such as dynamic contrast enhanced imaging or spectroscopy, we
      investigate the combination of T2-weighted imaging (T2w) and DWI as a potential
      diagnostic tool for prostate cancer detection, staging and guided biopsies.
      Quantification of the noise floor in the DWI images and careful fitting of the
      data suggests that the mono-exponential model provides a very good fit to the
      data and there is no evidence of non-Gaussian diffusion for b-values up to
      1000s/mm2. This precludes the use of kurtosis or other non-Gaussian measures as a
      biomarker for prostate cancer in our case. However, the ADC scores for healthy
      and probably malignant regions are significantly lower for the latter in all 20
      but one patient. The results suggest that a simplified mp-MRI protocol combining
      T2w and DWI may be a good compromise for a cost and time efficient, early-stage
      prostate cancer diagnostic programme, combining robust MR biomarkers for prostate
      cancer that can be reliably quantified and appear well-suited for general
      clinical practice.

PMID- 29183817
TI  - Structural characterization of a lepidopteran type-II farnesyl diphosphate
      synthase from the spruce budworm, Choristoneura fumiferana: Implications for
      inhibitor design.
AB  - Farnesyl diphosphate synthase (FPPS) is an enzyme from the class of short chain
      (E)-prenyltransferases that catalyzes the condensation of two molecules of
      isopentenyl diphosphate (IPP, C5) with dimethylallyl diphosphate (DMAPP, C5) to
      generate the C15 product FPP. In insects, FPPS plays a key role in the
      biosynthesis of the morphogenetic and gonadotropic "juvenile hormone" (JH).
      Lepidopteran genomes encode two very distinct FPPS paralogs, one of which ("type
      II") is expressed almost exclusively in the JH-producing glands, the corpora
      allata. This paralog has been hypothesized to display structural features that
      enable the binding of the bulkier precursors required for the biosynthesis of
      lepidopteran ethyl-branched JHs. Here, we report on the first crystal structures
      of an insect FPPS solved to date. Apo, ligand-bound, and inhibitor-bound
      structures of type-II FPPS (FPPS2) from the spruce budworm, Choristoneura
      fumiferana (Order: Lepidoptera), were obtained. Comparison of apo and inhibitor
      bound enzymes revealed differences in both inhibitor binding and structural
      plasticity of CfFPPS2 compared to other FPPSs. Our data showed that IPP is not
      essential to the closure of the C-terminal tail. Ortho-substituted pyridinium
      bisphosphonates, previously shown to inhibit CfFPPS2, bound to the allylic site,
      as predicted; however, their alkyl groups were oriented towards the homoallylic
      binding site, with the bulkier propyl-substituted inhibitor penetrating deeply
      into the IPP binding pocket. The current study sheds light on the structural
      basis of substrate specificity of type-II FPPS of the spruce budworm. Through a
      comparison with other inhibitor-bound FPPSs, we propose several approaches to
      improve inhibitor selectivity and potency.

PMID- 29183818
TI  - Federal and State Policy Efforts to Address Maternal Opioid Misuse: Gaps and
      Challenges.
AB  - BACKGROUND: Opioid misuse during pregnancy is increasingly common and is
      associated with preterm birth and neonatal abstinence syndrome. As such, there is
      increased policy attention on reducing opioid misuse and increasing detection and
      treatment of opioid use disorder around the time of childbirth. METHODS: We
      conducted a review of peer-reviewed and grey literature to identify policy
      strategies to address opioid misuse among pregnant women; to describe current
      federal and state laws that impact women before pregnancy, during pregnancy, at
      birth, and postpartum; and to identify gaps and challenges related to these
      efforts. RESULTS: We identify two gaps in current efforts: 1) limited attention
      to prevention of opioid misuse among reproductive-age women, and 2) lack of
      policies addressing opioid misuse among postpartum women. We also discuss
      barriers to accessing care for women who misuse opioids, including provider
      shortages (e.g., too few addiction medicine specialists accept pregnant women or
      Medicaid beneficiaries as patients), logistical barriers (e.g., lack of
      transportation, child care), stigma, and fear of legal consequences. CONCLUSIONS:
      As policymakers pursue strategies to address the opioid epidemic, the unique
      needs of pregnant and postpartum women and barriers to treatment should be
      addressed.

PMID- 29183820
TI  - MHC class II DRB diversity predicts antigen recognition and is associated with
      disease severity in California sea lions naturally infected with Leptospira
      interrogans.
AB  - We examined the associations between California sea lion MHC class II DRB (Zaca
      DRB) configuration and diversity, and leptospirosis. As Zaca-DRB gene sequences
      are involved with antigen presentation of bacteria and other extracellular
      pathogens, we predicted that they would play a role in determining responses to
      these pathogenic spirochaetes. Specifically, we investigated whether Zaca-DRB
      diversity (number of genes) and configuration (presence of specific genes)
      explained differences in disease severity, and whether higher levels of Zaca-DRB
      diversity predicted the number of specific Leptospira interrogans serovars that a
      sea lion's serum would react against. We found that serum from diseased sea lions
      with more Zaca-DRB loci reacted against a wider array of serovars. Specific Zaca
      DRB loci were linked to reactions with particular serovars. Interestingly, sea
      lions with clinical manifestation of leptospirosis that had higher numbers of
      Zaca-DRB loci were less likely to recover from disease than those with lower
      diversity, and those that harboured Zaca-DRB.C or -G were 4.5 to 5.3 times more
      likely to die from leptospirosis, regardless of the infective serovars. We
      propose that for leptospirosis, a disadvantage of having a wider range of antigen
      presentation might be increased disease severity due to immunopathology. Ours is
      the first study to examine the importance of Zaca-DRB diversity for antigen
      detection and disease severity following natural exposure to infective
      leptospires.

PMID- 29183819
TI  - SMFM Special Report: Putting the "M" back in MFM: Reducing racial and ethnic
      disparities in maternal morbidity and mortality: A call to action.
AB  - Racial and ethnic disparities in maternal morbidity and mortality rates are an
      important public health problem in the United States. Because racial and ethnic
      minorities are expected to comprise more than one-half of the US population by
      2050, this issue needs to be addressed urgently. Research suggests that the
      drivers of health disparities occur at 3 levels: patient, provider, and system.
      Although we have recognized this issue and identified elements that contribute to
      it, knowledge must be converted into action to address it. In addition, despite
      available funding and databases, research directed towards understanding and
      reducing these disparities is lacking. This document summarizes findings of a
      workshop convened at the 2016 Society for Maternal-Fetal Medicine's 36th Annual
      Pregnancy meeting in Atlanta, GA, to review and make recommendations about
      immediate actions in clinical care and research that will serve to reduce racial
      and ethnic disparities in maternal morbidity and mortality rates in the United
      States.

PMID- 29183821
TI  - Quality of life after total knee arthroplasty.
AB  - Total knee arthroplasty (TKA) results in a high degree of patient satisfaction,
      as it provides patients with considerable medium- and long-term benefits in terms
      of quality of life, pain relief and function. Nevertheless, the literature
      reports that up to 30% of patients are dissatisfied. This dissatisfaction is
      directly related to the patients' quality of life, which they deem insufficient.
      Their quality of life depends on many physical, behavioural, social and
      psychological factors that are not taken into account by functional outcome
      scores. After describing the principles of quality of life evaluation after TKA,
      we will assess the effects of patient-related factors, the surgical technique and
      postoperative program through an exhaustive review of the literature. Patient
      expectations after TKA will then be outlined, particularly return to work and
      return to sports.

PMID- 29183822
TI  - Treatment of aseptic tibial shaft non-union without bone defect.
AB  - Non-union is incomplete consolidation of a fracture, without effective formation
      of a uniting callus. Despite better understanding of the physiology of bone
      consolidation, management of tibial non-union remains a challenge for orthopedic
      surgeons. Several treatments have been developed in recent decades, and we now
      have a range of techniques, with indications based on type of non-union, prior
      treatments, available equipment, and the surgeon's experience. Firstly, there are
      surgical techniques such as osteo-periosteal decortication, cancellous iliac
      graft, or inter-tibiofibular graft. The decision to fix the non-union (or revise
      existing fixation) and choice of type of internal fixation depend on the
      stability of the fracture site. There are also non-operative biological and
      biochemical consolidation stimulation techniques: local injection of bone-marrow,
      platelet-rich plasma (PRP) or bone morphogenetic protein (BMP). Stimulation can
      also be physical, applying ultrasound or an electromagnetic field to the non
      union site. Each technique may be used in isolation or association.

PMID- 29183823
TI  - Lip reconstruction technique: A modified Abbe-Estlander with a myomucosal
      advancement flap.
AB  - Lip cancer represents between 12-15% of all oral cavity cancers; 95% affect the
      lower lip. The main objectives in lip reconstruction after tumoral mass resection
      are functionality and esthetics. We present the case of an 81-year-old male with
      a past medical history of squamous cell carcinoma of the maxilla. The patient
      consults with the Maxillofacial Surgery Department due to a hypertrophic lesion
      in the left oral commissure. The defect is considered intermediate in size
      (between 50% and two-thirds). For reconstruction of the lip, a classical rotation
      flap (Estlander flap) is used together with a myomucosal flap, which is both
      innervated and expandable. According to medical literature, for intermediate
      defects of the lower lip advancement or rotation flaps should be used. One of
      these is the Abbe-Estlander flap, a rotation flap dependent of the superior or
      the inferior labial artery. The Karapandzic flap and Johansen's staircase flap
      are other recommended techniques.

PMID- 29183824
TI  - Zika virus infection in travelers returning from countries with local
      transmission, Guangdong, China, 2016.
AB  - BACKGROUND: Zika virus (ZIKV) is a mosquito-borne virus spreading rapidly in the
      Americas, Africa, and Asia. No indigenous ZIKV infection had been seen in China.
      We monitored ZIKV infection among travelers returning to Enping county from ZIKV
      transmitting countries from 1 March to 10 April 2016. METHODS: We analyzed data
      including interviews; conducted laboratory test on blood, urine, saliva,
      conjunctival swab or semen specimens for evidence of ZIKV infection; evaluated
      household for presence of Aedes mosquitoes or larvae. RESULTS: A total of 925
      individuals were screened, 507 (54.8%) were interviewed, 400 (43.2%) provided
      samples, of which 13 (3.3%) tested positive for ZIKV including 3 asymptomatic.
      Rash, conjunctivitis, sore throat, fever were the common symptoms; rash was more
      pronounced in adults than in children. ZIKV RNA was detected for 1-4 days in
      blood, but longer in urine and saliva (3-32 days and 2-10 days). Among
      interviewed, 57.0% had good knowledge about ZIKV, 45.8% were worried about ZIKV,
      99.2% would go to hospital if they had infection. Aedes mosquitoes or larvae were
      detected in townships of infected returners. CONCLUSIONS: ZIKV was imported to
      China. Screening by symptoms alone is inadequate for detecting ZIKV infection.
      ZIKV surveillance, health-education, and vector control are necessary to decrease
      risk of ZIKV transmission.

PMID- 29183825
TI  - Chronic Intranasal Oxytocin has Dose-dependent Effects on Central Oxytocin and
      Vasopressin Systems in Prairie Voles (Microtus ochrogaster).
AB  - Oxytocin (Oxt) is a neuropeptide with many functions, including modulation of
      social behavior(s) and anxiety. Due to its notable pro-social effects, it has
      been proposed as a treatment in the management of neuropsychiatric disorders,
      such as autism spectrum disorder (ASD), schizophrenia, and social anxiety;
      however, effects of long-term daily treatment are still being explored.
      Previously, we have shown that in male prairie voles (Microtus ochrogaster)
      exposure to Oxt during the peri-adolescent period impaired adult pair bonding in
      a dose-dependent fashion. In females, the medium dose used (0.8 IU/kg) appeared
      to facilitate pair bonding, and the low and medium doses were associated with
      fewer lines crossed in the open field. In this study, we examined central
      receptor binding and immunoreactive (IR) protein for Oxt and vasopressin (Avp), a
      closely related peptide. Voles were treated with saline vehicle, or one of three
      doses of Oxt (0.08, 0.8, 8.0 IU/kg) for three weeks from postnatal days 21 to 42,
      and euthanized as adults. We used autoradiography to examine Oxt and Avp receptor
      binding and immunohistochemistry to examine Oxt and Avp - IR cells in the
      paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Females
      that received the medium dose of Oxt had higher Oxt receptor binding in the
      nucleus accumbens shell (NAS), while males that received the medium dose had
      lower Avp-IR cells in the PVN. In summary, we found sex-specific effects of long
      term exposure to intranasal Oxt on the Oxt and Avp systems at the weight-adjusted
      dose currently being used in clinical trials in humans.

PMID- 29183827
TI  - Complex Environmental Rearing Enhances Social Salience and Affects Hippocampal
      Corticotropin Releasing Hormone Receptor Expression in a Sex-Specific Manner.
AB  - Methods for understanding the neurocircuitry of ethologically relevant behaviors
      have advanced substantially; however renovations to standard animal laboratory
      housing, in the form of enhanced enrichment, have lagged behind. This is despite
      evidence that environmental enrichment (EE) reduces stress, stereotypy, and
      promotes healthy species typical behaviors. While many scientists express
      interest for increased EE as a standard for animal caging systems, there are
      concerns that its effects on brain, behavior, and cognition are not well
      characterized. In the present study, male and female Sprague-Dawley rats were
      housed for six weeks in either EE, Colony Nesting (CN), or Standard Housing (SD)
      conditions. We show that adolescent exposure to environmental complexity changed
      the dynamics of social interactions, sensory processing, and underlying basal
      stress neurocircuitry, in a sex- and enrichment-type-dependent manner.
      Specifically, EE and CN increased prosocial engagement and the social saliency of
      male and female rats while the profile of hippocampal Crhr2 expression was
      affected only in EE males. Hippocampal Crh was associated with anxiety-like
      behavior in SD males - this did not extend to EE or CN groups, nor to females.
      Observations such as these are an important consideration for the validity of
      translational research investigating the neurocircuitry of stress resiliency, and
      for understanding the mechanisms of psychiatric disorders. Future work must focus
      on characterizing how individual environmental enhancements (e.g. novelty, social
      enrichment, physical activity) shape phenotypic differences, how they vary as a
      function of species, strain and sex, and (if warranted) how to meaningfully
      implement this knowledge into biomedical research designs.

PMID- 29183826
TI  - Developmental Ethanol-Induced Sleep Fragmentation, Behavioral Hyperactivity,
      Cognitive Impairment and Parvalbumin Cell Loss are Prevented by Lithium Co
      treatment.
AB  - Developmental ethanol exposure is a well-known cause of lifelong cognitive
      deficits, behavioral hyperactivity, emotional dysregulation, and more. In healthy
      adults, sleep is thought to have a critical involvement in each of these
      processes. Our previous work has demonstrated that some aspects of cognitive
      impairment in adult mice exposed at postnatal day 7 (P7) to ethanol (EtOH)
      correlate with slow-wave sleep (SWS) fragmentation (Wilson et al., 2016). We and
      others have also previously demonstrated that co-treatment with LiCl on the day
      of EtOH exposure prevents many of the anatomical and physiological impairments
      observed in adults. Here we explored cognitive function, diurnal rhythms
      (activity, temperature), SWS, and parvalbumin (PV) and perineuronal net (PNN)
      positive cell densities in adult mice that had received a single day of EtOH
      exposure on P7 and saline-treated littermate controls. Half of the animals also
      received a LiCl injection on P7. The results suggest that developmental EtOH
      resulted in adult behavioral hyperactivity, cognitive impairment, and reduced SWS
      compared to saline controls. Both of these effects were reduced by LiCl treatment
      on the day of EtOH exposure. Finally, developmental EtOH resulted in decreased
      PV/PNN-expressing cells in retrosplenial (RS) cortex and dorsal CA3 hippocampus
      at P90. As with sleep and behavioral activity, LiCl treatment reduced this
      decrease in PV expression. Together, these results further clarify the long
      lasting effects of developmental EtOH on adult behavior, physiology, and anatomy.
      Furthermore, they demonstrate the neuroprotective effects of LiCl co-treatment on
      this wide range of developmental EtOH's long-lasting consequences.

PMID- 29183828
TI  - Musical Expectations Enhance Auditory Cortical Processing in Musicians: A
      Magnetoencephalography Study.
AB  - The present study investigated the influence of musical expectations on auditory
      representations in musicians and non-musicians using magnetoencephalography
      (MEG). Neuroscientific studies have demonstrated that musical syntax is processed
      in the inferior frontal gyri, eliciting an early right anterior negativity
      (ERAN), and anatomical evidence has shown that interconnections occur between the
      frontal cortex and the belt and parabelt regions in the auditory cortex (AC).
      Therefore, we anticipated that musical expectations would mediate neural
      activities in the AC via an efferent pathway. To test this hypothesis, we
      measured the auditory-evoked fields (AEFs) of seven musicians and seven non
      musicians while they were listening to a five-chord progression in which the
      expectancy of the third chord was manipulated (highly expected, less expected,
      and unexpected). The results revealed that highly expected chords elicited
      shorter N1m (negative AEF at approximately 100 ms) and P2m (positive AEF at
      approximately 200 ms) latencies and larger P2m amplitudes in the AC than less
      expected and unexpected chords. The relations between P2m amplitudes/latencies
      and harmonic expectations were similar between the groups; however, musicians'
      results were more remarkable than those of non-musicians. These findings suggest
      that auditory cortical processing is enhanced by musical knowledge and long-term
      training in a top-down manner, which is reflected in shortened N1m and P2m
      latencies and enhanced P2m amplitudes in the AC.

PMID- 29183829
TI  - The Rodent-versus-wild Snake Paradigm as a Model for Studying Anxiety- and Panic
      like Behaviors: Face, Construct and Predictive Validities.
AB  - Using an innovative approach to study the neural bases of psychiatric disorders,
      this study investigated the behavioral, morphological and pharmacological bases
      of panic attack-induced responses in a prey-versus-coral snake paradigm.
      Mesocricetus auratus was chronically treated with intraperitoneal administration
      of the selective serotonin uptake inhibitor paroxetine or the gamma aminobutyric
      acid (GABA)/benzodiazepine receptor agonist alprazolam at three different doses
      and were then confronted with a venomous coral snake (Micrurus frontalis,
      Reptilia, Elapidae). The threatened rodents exhibited defensive attention, flat
      back approaches, defensive immobility, and escape defensive responses in the
      presence of the venomous snake, followed by increases in Fos protein in limbic
      structure neurons. Chronic administration of both paroxetine and alprazolam
      decreased these responses with morphological correlates between the panicolytic
      effect of both drugs administered at the highest dose and decreases in Fos
      protein-immunolabeled perikarya found in the amygdaloid complex, hypothalamus and
      periaqueductal gray matter columns, which are structures that make up the
      encephalic aversion system. These findings provide face, construct and predictive
      validities of this new experimental model of anxiety- and panic attack-like
      behavioral responses displayed by threatened prey confronted with venomous coral
      snakes.

PMID- 29183830
TI  - Improving cannulation time for extracorporeal life support in refractory cardiac
      arrest of presumed cardiac cause - Comparison of two percutaneous cannulation
      techniques in the catheterization laboratory in a center without on-site
      cardiovascular surgery.
AB  - BACKGROUND: Cardiac arrest (CA) without return of spontaneous circulation can be
      treated with veno-arterial extracorporeal membrane oxygenation (vaECMO)
      implemented surgically or percutaneously. We performed a study assessing time for
      vaECMO percutaneous cannulation in the catheterization laboratory. METHODS:
      Single-centre retrospective study in a University hospital without on-site
      cardiovascular surgery, including patients aged >18 receiving vaECMO for out- or
      in-hospital refractory CA of presumed cardiac cause between 2010 and 2016,
      cannulated by interventional cardiologists. Cannulation time using anatomic
      landmarks vessel puncture and conventional wires (first period) was compared with
      ultrasound guidance puncture and stiff wires (second period). Data are expressed
      as medians (interquartile range) and percentages. RESULTS: Forty-six patients
      were included, age 56 (49-62), 34 in the first period. Shockable initial rhythm
      occurred in 29 (63%), 36 (78%) had ischemic heart disease and 26 (57%) acute
      myocardial infarction (AMI). Out-of-hospital refractory CA occurred in 27 (59%)
      patients. Time from out-of-hospital refractory CA to admission was 100 (80-118)
      min. Cannulation was successful in 42 (91%) patients. Cannulation time was 14 (10
      21) min, 17 (12-26) (first) and 8 (6-12) min (second period), p<0.001. Survival
      to discharge was 9%. In out-of-hospital versus in-hospital, time from CA to
      vaECMO was 120 (115-140) versus 82 (58-102) min, p=0.011, survival was 7% (two
      patients) versus 11% (two patients), p=0.35 respectively. All survivors had
      shockable initial rhythm. CONCLUSION: In these refractory CA patients with high
      prevalence of AMI and good feasibility of percutaneous vaECMO in the
      catheterization laboratory, cannulation time was shorter using ultrasound
      guidance and stiff wires.

PMID- 29183831
TI  - 'She's sort of breathing': What linguistic factors determine call-taker
      recognition of agonal breathing in emergency calls for cardiac arrest?
AB  - BACKGROUND: In emergency ambulance calls, agonal breathing remains a barrier to
      the recognition of out-of-hospital cardiac arrest (OHCA), initiation of
      cardiopulmonary resuscitation, and rapid dispatch. We aimed to explore whether
      the language used by callers to describe breathing had an impact on call-taker
      recognition of agonal breathing and hence cardiac arrest. METHODS: We analysed
      176 calls of paramedic-confirmed OHCA, stratified by recognition of OHCA (89
      cases recognised, 87 cases not recognised). We investigated the linguistic
      features of callers' response to the question "is s/he breathing?" and examined
      the impact on subsequent coding by call-takers. RESULTS: Among all cases
      (recognised and non-recognised), 64% (113/176) of callers said that the patients
      were breathing (yes-answers). We identified two categories of yes-answers: 56%
      (63/113) were plain answers, confirming that the patient was breathing ("he's
      breathing"); and 44% (50/113) were qualified answers, containing additional
      information ("yes but gasping"). Qualified yes-answers were suggestive of agonal
      breathing. Yet these answers were often not pursued and most (32/50) of these
      calls were not recognised as OHCA at dispatch. CONCLUSION: There is potential for
      improved recognition of agonal breathing if call-takers are trained to be alert
      to any qualification following a confirmation that the patient is breathing.

PMID- 29183832
TI  - Practice of umbilical venous catheterization using a resource-efficient 'blended'
      training model.

PMID- 29183833
TI  - Uncontrolled donation programs after out-of-hospital cardiac arrest. An
      estimation of potential donors.
AB  - OBJECTIVE: To determine the number of potential deceased organ donors from out-of
      hospital cardiac arrest cases (OHCA) attended by public physician-led emergency
      medical services in Spain, based on data recorded in the nationwide Spanish OHCA
      Registry (OHSCAR). MATERIAL AND METHODS: We analysed OHSCAR data on deceased OHCA
      patients in Spain during 13 months (1/10/2013 to 31/10/2014). Variables included
      age, sex, estimated OHCA time, cardiopulmonary resuscitation (CPR) start time and
      outcome. Inclusion criteria were: age 16-60 years, witnessed OHCA, no return of
      spontaneous circulation (ROSC) and time interval <15min between OHCA occurrence
      and CPR initiation. RESULTS: Of a total 8789 cases, 3290 met the age criteria; of
      these, CPR was not witnessed in 745 cases. Among the remaining 2545 patients, 141
      were included in uncontrolled donation after cardiac death (uDCD) programs, 902
      arrived at the hospital with ROSC, 64 arrived with ongoing CPR and 15 cases were
      lost to follow-up. Of the remaining 1423 without ROSC, CPR initiation time was
      not recorded in 454 cases and 398 did not meet the time criteria <15min between
      OHCA and CPR initiation. Finally, 571 met all the criteria and could have been
      potential donors. There were significant differences in the actual donors
      percentage from potential donors percentage between provinces with and without
      donor programs (141/322=43.8% versus 0/390=0%), but there were no differences in
      ROSC between the two types of provinces (418/1320=31.7% versus 652/1970=33.4%).
      CONCLUSIONS: Many potential donors are missed in current clinical practice. uDCD
      programs are few and underused even in a country with high rates of organ
      transplantation.

PMID- 29183834
TI  - Contact lens to measure individual ion concentrations in tears and applications
      to dry eye disease.
AB  - Dry eye disease (DED) affects millions of individuals in the United States and
      worldwide, and the incidence is increasing with an aging population. There is
      widespread agreement that the measurement of total tear osmolarity is the most
      reliable test, but this procedure provides only the total ionic strength and does
      not provide the concentration of each ionic species in tears. Here, we describe
      an approach to determine the individual ion concentrations in tears using modern
      silicone hydrogel (SiHG) contact lenses. We made pH (or H3O+, hydronium
      cation,/OH-, hydroxyl ion) and chloride ion (two of the important electrolytes in
      tear fluid) sensitive SiHG contact lenses. We attached hydrophobic C18 chains to
      water-soluble fluorescent probes for pH and chloride. The resulting hydrophobic
      ion sensitive fluorophores (H-ISF) bind strongly to SiHG lenses and could not be
      washed out with aqueous solutions. Both H-ISFs provide measurements which are
      independent of total intensity by use of wavelength-ratiometric measurements for
      pH or lifetime-based sensing for chloride. Our approach can be extended to
      fabricate a contact lens which provides measurements of the six dominant ionic
      species in tears. This capability will be valuable for research into the
      biochemical processes causing DED, which may improve the ability to diagnose the
      various types of DED.

PMID- 29183835
TI  - Antinociceptive effects of mixtures of mu opioid receptor agonists and
      cannabinoid receptor agonists in rats: Impact of drug and fixed-dose ratio.
AB  - Pain is a significant clinical problem, and there is a need for effective
      pharmacotherapies with fewer adverse effects than currently available drugs
      (e.g., mu opioid receptor agonists). Cannabinoid receptor agonists enhance the
      antinociceptive effects of mu opioid receptor agonists, but it remains unclear
      which drugs and in what proportion will yield the most effective and safest
      treatments. The antinociceptive effects of the mu opioid receptor agonists
      etorphine and morphine alone and in combination with the cannabinoid receptor
      agonists Delta9-THC and CP55940 were studied in male Sprague-Dawley rats (n = 16)
      using a warm water tail withdrawal procedure. The ratio of opioid to cannabinoid
      (3:1, 1:1, and 1:3) varied for each mixture. Drugs administered alone or as
      pairwise mixtures of an opioid and a cannabinoid dose-dependently increased tail
      withdrawal latency. Mixtures with morphine produced supra-additive (CP55940) and
      additive (Delta9-THC) effects, whereas mixtures with etorphine and either
      cannabinoid were sub-additive. The interactions were not different among ratios
      for a particular mixture. The nature of the interaction between opioids and
      cannabinoids with regard to antinociceptive effects varies with the particular
      drugs in the mixture, which can have implications for designing combination
      therapies for pain.

PMID- 29183836
TI  - An update on vinpocetine: New discoveries and clinical implications.
AB  - Vinpocetine, a derivative of the alkaloid vincamine, has been clinically used in
      many countries for treatment of cerebrovascular disorders such as stroke and
      dementia for more than 30 years. Currently, vinpocetine is also available in the
      market as a dietary supplement to enhance cognition and memory. Due to its
      excellent safety profile, increasing efforts have been put into exploring the
      novel therapeutic effects and mechanism of actions of vinpocetine in various cell
      types and disease models. Recent studies have revealed a number of novel
      functions of vinpocetine, including anti-inflammation, antagonizing injury
      induced vascular remodeling and high-fat-diet-induced atherosclerosis, as well as
      attenuating pathological cardiac remodeling. These novel findings may facilitate
      the repositioning of vinpocetine for preventing or treating relevant disorders in
      humans.

PMID- 29183837
TI  - Melatonin inhibits rotenone-induced SH-SY5Y cell death via the downregulation of
      Dynamin-Related Protein 1 expression.
AB  - Previous studies have shown that melatonin can protect cells against rotenone
      induced cell death. Yet, the mechanism involved in this protection requires
      further research. In this study, we aimed to further investigate the effects of
      melatonin on inhibiting rotenone-induced SH-SY5Y cells and the underlying
      molecular mechanisms. Human neuroblastoma SH-SY5Y cells were treated with 0.3 or
      1MUM rotenone for 6 or 12h. Cell viability was measured with an MTS assay, the
      mitochondrial membrane potential was determined with a Rhodamine 123 staining
      assay, and the protein expression levels of the markers of autophagy, including
      cytochrome C release (Cyt C), light chain 3B (LC3 B) and Dynamin-Related Protein
      1 (Drp1) were analyzed by western blotting. The co-localization of Drp1 and TOM20
      proteins in the mitochondria of SH-SY5Y cells was measured by immunofluorescence
      coupled with confocal microscopy and the overexpression of the Drp1 gene was then
      conducted. The viability and expression levels of Cyt C and LC3 B in rotenone and
      melatonin + rotenone-treated Drp1-overexpressed SH-SY5Y cells were analyzed with
      MTS and western blotting, respectively. We found that rotenone effectively
      induced SH-SY5Y cell death by causing mitochondrial dysfunction and increasing
      Cyt C expression. Drp1 expression and its regulation of mitochondrial
      translocation mediated the rotenone-induced cell death and melatonin inhibited
      this process. Overexpression of Drp1 protein attenuated melatonin's inhibition of
      rotenone-induced SH-SY5Y cell death. In conclusion, melatonin effectively
      inhibits rotenone-induced neuronal cell death via the regulation of Drp1
      expression.

PMID- 29183838
TI  - Abediterol (LAS100977), an inhaled long-acting beta2-adrenoceptor agonist, has a
      fast association rate and long residence time at receptor.
AB  - This study describes the association rate and residence time of abediterol, a
      novel long-acting beta2-adrenoceptor agonist (LABA) in Phase II development for
      treatment of asthma and COPD, in comparison with indacaterol, olodaterol,
      vilanterol and salmeterol, for both human beta1- and beta2-adrenoceptors.
      Abediterol association and dissociation rates were monitored directly by using
      its tritiated form. Moreover, association was determined indirectly using
      experimental Ki and koff obtained from assays performed with unlabelled compound.
      Dissociation was also studied indirectly by measuring the association rate of 3H
      CGP12177 to beta adrenoceptors previously occupied by unlabelled compounds.
      Abediterol shows a fast association for the beta2-adrenoceptor (kon 1.4 * 107 +/-
      1.8 * 106M-1min-1) while its dissociation rate is between 30 and 64 times slower
      than that of the reference LABA compounds tested, with a residence time of 91.3
      +/- 13.3min (measured directly) and 185.5 +/- 7.5min (measured indirectly).
      Abediterol shows kinetic selectivity for the beta2- over the beta1-adrenoceptor,
      with a dissociation rate from the beta1-adrenoceptor similar to the other LABA
      compounds tested. In conclusion, abediterol is a potent LABA with a fast
      association rate and a long residence time at beta2-adrenoceptors. These data are
      in agreement with the onset and duration of action of abediterol shown in humans.

PMID- 29183839
TI  - The role of ethyl acrylate induced GSH depletion in the rodent forestomach and
      its impact on MTD and in vivo genotoxicity in developing an adverse outcome
      pathway (AOP).
AB  - Adverse outcome pathways (AOP) and mode of action (MOA) frameworks help evaluate
      the toxicity findings of animal studies and their relevance to humans. To
      effectively use these tools to improve hazard identification and risk assessments
      for ethyl acrylate (EA), knowledge gaps in metabolism and genotoxicity were
      identified and addressed. For EA, hypothesized early key events relate to its
      irritation potential: concentration dependent irritation and cytotoxicity,
      progressing to regenerative proliferation and forestomach carcinogenicity after
      repeated oral bolus application in rodents. The current research quantitated
      glutathione (GSH) depletion to assess a kinetically-derived maximum tolerated
      dose (MTD) in the target tissue and used this information to conduct an in vivo
      genotoxicity study using current methods. In the mouse forestomach, gavage doses
      of EA caused GSH depletion to 47% of control at 20 mg/kg and 28% at 100 mg/kg.
      Cellular redox changes and histopathology support saturation of metabolism and an
      MTD of ~50 mg/kg. No increases in point mutations or deletions occurred in the
      stomach or liver following a 28 day treatment of gpt delta transgenic mice at
      gavage doses up to 50 mg/kg/day. These results provide valuable information for
      evaluating AOP molecular initiating events or MOA key events for EA and other GSH
      depleting materials.

PMID- 29183840
TI  - Comparative expression analyses of bone morphogenetic protein 4 (BMP4)
      expressions in muscles of tilapia and common carp indicate that BMP4 plays a role
      in the intermuscular bone distribution in a dose-dependent manner.
AB  - Intermuscular bones in fish negatively influence both meet processing and
      attractiveness to consumers. Tilapia (Oreochromis niloticus) and common carp
      (Cyprinus carpio) are both major farmed fish species globally, but whereas the
      former does not possess intermuscular bones, the latter does. Therefore, these
      two species might present a good model to study the genetic control of
      distribution of intermuscular bones in fish. Bone morphogenetic protein 4 (BMP4)
      gene is associated with tissue ossification and bone regeneration in mammals, but
      in fish its role in ossification remains understudied. To study the relationship
      between BMP4 and bone distribution in fish, we determined the expression of BMP4
      in muscle tissues of common carp and tilapia on transcriptional and translational
      levels. As the gene has been merely predicted in silico from the genome of common
      carp, we have cloned and characterized it. The gene (GenBank: HQ446455) contains
      one intron and two exons, which encode a 400-amino acid protein with high
      homology to other known BMP4 protein sequences. Phylogenetic analysis showed that
      common carp clustered within the Cypriniformes clade (zebrafish was the closest
      ortholog) and tilapia within the Percomorpha clade. Using microCT scanning, we
      confirmed that intermuscular bones could be observed only in common carp (none in
      tilapia), but only in dorsal and caudal muscles (none in the ventral muscle).
      Expression levels of BMP4 in the muscles of common carp were in agreement with
      this observation both on transcriptional (qPCR) and translational
      (immunohistochemistry) level: higher in dorsal and caudal muscles, and lower in
      the ventral muscle. In tilapia, expression of BMP4 gene was also detectable in
      all three muscles, but expression levels in all three muscles were comparable to
      the one observed in the ventral muscle of carp, i.e., very low. Therefore, among
      the six studied muscles, the expression of BMP4 was high only in the two that
      possess intermuscular bones: dorsal and caudal muscles of common carp. The
      results of this study suggest that BMP4 is likely to play a key role in the
      determination of intermuscular bone distribution in fish in a dose-dependent
      manner.

PMID- 29183841
TI  - Prevalence and genetic diversity of human diarrheagenic Escherichia coli isolates
      by multilocus sequence typing.
AB  - BACKGROUND: The population structure of human diarrheagenic Escherichia coli
      (DEC) isolates derived from worldwide collections remains undefined. METHODS: A
      total of 1196 clinical isolates were obtained from a multilocus sequence typing
      (MLST) database. Genetic diversity analysis, MLST analysis, and phylogenetic
      analysis combined with different pathotypes were performed through a variety of
      calculation software applications. RESULTS: All isolates were categorized as one
      of 579 different sequence types (STs). The eBURST algorithm resolved these 579
      STs into 27 clonal complexes (CCs), 37 concatemers, and 210 singletons, revealing
      a high level of genetic diversity in the population structure of DEC. CC10 was
      the most prevalent CC, comprising 276 (23.08%, 276/1196) isolates with 85
      (14.68%, 85/579) STs widely distributed in 20 countries. The population structure
      of five common pathotypes was highly diversified, and isolates with the same ST
      or CC were heterogeneous for different pathotypes. Sequence variations were more
      abundant in fumC and gyrB than in the other five genes, and these exhibited the
      highest degree of nucleotide diversity (0.03886 and 0.03075, respectively) and
      the greatest number of polymorphic nucleotide sites (137 and 139, respectively).
      The dN/dS ratios of seven analyzed loci varied from 0.0083 (recA) to 0.0434
      (purA), and the ratio for the concatenated sequence was 0.2518, revealing the
      effects of purifying selection on housekeeping genes during the evolutionary
      process. Significant allele linkage disequilibrium was detected when the
      standardized index of association (ISA) was calculated both for the entire
      collection of isolates (0.3174, p<0.001) and for the 579 STs (0.1475, p<0.001).
      CONCLUSIONS: This study facilitated a comprehensive understanding of the genetic
      diversity of human DEC distributed across the global population. The results
      provide genetic evidence that will allow us to uncover the microevolutionary
      relationships among different pathogenic isolates of DEC.

PMID- 29183842
TI  - Systematic review of seroepidemiological studies on Japanese encephalitis in the
      Republic of Korea.
AB  - BACKGROUND: Countries with strong vaccination programmes, including the Republic
      of Korea, have experienced changes in the epidemiology of Japanese encephalitis
      (JE), with an increase in cases seen among adults. However, the reasons for this
      increase are not clearly understood. This study describes the change in age
      specific JE virus (JEV) seroprevalence over time in Korea, with a view to
      understanding this transition. METHODS: A search of Embase, MEDLINE, PubMed,
      KoreaMed, Korea Education and Research Information Service, National Library of
      Korea, and the Seoul National University Medical Library was conducted using the
      keywords 'Japanese encephalitis' combined with 'Korea', 'seroprevalence',
      'seropositivity', 'seroepidemiology', 'serosurvey', 'immunity', and 'antibody'.
      RESULTS: Eighteen studies published between 1946 and 2012 were retrieved. In
      1946, seropositivity was 51% in the 1-10 years age group, 79% in those aged 11-20
      years, and 94% in those >=61 years of age. In the 1970s, seropositivity in
      children and adolescents was low (10-59%); seropositivity in this group increased
      to 90-92% in 1984-1985, and increased further to 98% in 2012. Seropositivity
      among adults aged 41-50 years and 51-60 years in the 2010s ranged between 83.1%
      and 97.9% and between 77.5% and 98.3%, respectively. CONCLUSIONS: The
      implementation of the universal JE vaccination programme in the 1980s has
      increased the seroprevalence of JEV in Korea, especially in children who are
      targeted for vaccination.

PMID- 29183843
TI  - The Montreal Cognitive Assessment-Basic (MoCA-B) is not a reliable screening tool
      for cognitive decline in HIV patients receiving combination antiretroviral
      therapy in rural South Africa.
AB  - BACKGROUND: HIV-associated neurocognitive disorders (HAND) are frequently
      occurring comorbidities in HIV-positive patients, diagnosed by means of a
      neuropsychological assessment (NPA). Due to the magnitude of the HIV-positive
      population in Sub-Saharan Africa, easy-to-use cognitive screening tools are
      essential. METHODS: This was a cross-sectional clinical trial involving 44 HIV
      positive patients (on stable cART) and 73 HIV-negative controls completing an
      NPA, the International HIV Dementia Scale (IHDS), and a culturally appropriate
      cognitive screening tool, the Montreal Cognitive Assessment-Basic (MoCA-B). HAND
      were diagnosed by calculating Z-scores using internationally published normative
      data on NPA, as well as by using data from the HIV-negative group to validate the
      MoCA-B. RESULTS: One hundred and seventeen patients were included (25% male,
      median age 35 years, median 11 years of education). A moderate correlation was
      found between the MoCA-B and NPA total Z-score (Pearson's r=0.36, p=0.02). Area
      under the curve (AUC) values for MoCA-B and IHDS were 0.59 and 0.70,
      respectively. The prevalence of HAND in HIV-positive patients was 66% when
      calculating Z-scores using published normative data versus 48% when using the
      data from the present HIV-negative cohort. CONCLUSION: The MoCA-B appeared not to
      be a valid screening tool for HAND in this setting. The prevalence of HAND in
      this setting is high, but appeared overestimated when using published norms.

PMID- 29183844
TI  - Original paper: Efficacy and safety analysis of insulin degludec/insulin aspart
      compared with biphasic insulin aspart 30: A phase 3, multicentre, international,
      open-label, randomised, treat-to-target trial in patients with type 2 diabetes
      fasting during Ramadan.
AB  - AIMS: To compare the efficacy and safety of insulin degludec/insulin aspart
      (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) before, during and after
      Ramadan in patients with type 2 diabetes mellitus (T2DM) who fasted during
      Ramadan. METHODS: In this multinational, randomised, treat-to-target trial,
      patients with T2DM who intended to fast and were on basal, pre- or self-mixed
      insulin +/- oral antidiabetic drugs for >=90 days were randomised (1:1) to
      IDegAsp twice daily (BID) or BIAsp 30 BID. Treatment period included pre-Ramadan
      treatment initiation (with insulin titration for 8-20 weeks), Ramadan (4 weeks)
      and post-Ramadan (4 weeks). Insulin doses were reduced by 30-50% for the pre-dawn
      meal (suhur) on the first day of Ramadan, and readjusted to the pre-Ramadan
      levels at the end of Ramadan. Hypoglycaemia was analysed as overall (severe or
      plasma glucose <3.1 mmol/L [56 mg/dL]), nocturnal (00:01-05:59) or severe
      (requiring assistance of another person). RESULTS: During the treatment period,
      IDegAsp (n = 131) had significantly lower overall and nocturnal hypoglycaemia
      rates with similar glycaemic efficacy, versus BIAsp 30 (n = 132). During Ramadan,
      despite achieving significantly lower pre-iftar (meal at sunset) self-measured
      plasma glucose (estimated treatment difference: -0.54 mmol/L [-1.02; -0.07]95%
      CI, p = .0247; post hoc) with similar overall glycaemic efficacy, IDegAsp showed
      significantly lower overall and nocturnal hypoglycaemia rates versus BIAsp 30.
      CONCLUSIONS: IDegAsp is a suitable therapeutic agent for patients who need
      insulin for sustained glucose control before, during and after Ramadan fasting,
      with a significantly lower risk of hypoglycaemia, versus BIAsp 30, an existing
      premixed insulin analogue.

PMID- 29183846
TI  - Do we still need ICDs if we have ARNi?

PMID- 29183845
TI  - Comparison of adiposity indicators associated with fasting-state insulinemia,
      triglyceridemia, and related risk biomarkers in a nationally representative,
      adult population.
AB  - AIMS: We hypothesized that height-corrected abdominal size (supine sagittal
      abdominal diameter/height ratio [SADHtR] or waist circumference/height ratio
      [WHtR]) would associate more strongly than body mass index (BMI, weight/height2)
      with levels of fasting insulin, triglycerides, and three derived biomarkers of
      insulin resistance. METHODS: Anthropometry, including SAD by caliper, was
      collected on 4398 adults in the 2011-2014 National Health and Nutrition
      Examination Survey. For comparison purposes, each adiposity indicator was scaled
      to its population-based, sex-specific, interquartile range (IQR). For each
      biomarker we created four outcome groups based on equal-sized populations with
      ascending values. Multivariable polytomous logistic regression modeled the
      relationships between the adiposity indicators and each biomarker. RESULTS:
      Highest-group insulin was associated with a one-IQR increment of BMI (RR 4.3 [95%
      CI 3.9-4.9]), but more strongly with a one-IQR increment of SADHtR (RR 5.7 [5.0
      6.6]). For highest-group HOMA-IR the RR for BMI (4.2 [3.7-4.6]) was less than
      that of SADHtR (6.0 [5.1-7.0]). Similarly, RRs for BMI were smaller than those
      for SADHtR applying to highest-group triglycerides (RR 1.6 vs 2.1),
      triglycerides/HDL-cholesterol (RR 1.9 vs 2.4) and TyG index (RR 1.7 vs 2.2) (all
      p < .001). The RRs for WHtR were consistently between those for SADHtR and BMI.
      The top 25% of insulin resistance among US adults was estimated to lie above
      adiposity thresholds of 0.140 for SADHtR, 0.606 for WHtR, or 29.6 kg/m2 for BMI.
      CONCLUSIONS: Relative abdominal size rather than relative weight may better
      define adiposity associated with homeostatic insulin resistance. These population
      based, cross-sectional findings could improve anthropometric prediction of
      cardiometabolic risk.

PMID- 29183847
TI  - Breath figures in tissue engineering and drug delivery: State-of-the-art and
      future perspectives.
AB  - : The breath figure (BF) method is an easy, low-cost method to prepare films with
      a highly organized honeycomb-like porous surface. The particular surface
      topography and porous nature of these materials makes them valuable substrates
      for studying the complex effects of topography on cell fate, and to produce
      biomimetic materials with high performance in tissue engineering. Numerous
      researchers over the last two decades have studied the effects of the honeycomb
      topography on a variety of primary and immortalized cell lines, and drew
      important conclusions that can be translated to the construction of optimal
      biomaterials for cell culture. The literature also encouragingly shows the
      potential of honeycomb films to induce differentiation of stem cells down a
      specific lineage without the need for biochemical stimuli. Here, we review the
      main studies where BF honeycomb films are used as substrates for tissue
      engineering applications. Furthermore, we highlight the numerous advantages of
      the porous nature of the films, such as the enhanced, spatially controlled
      adsorption of proteins, the topographical cues influencing cellular behavior, and
      the enhanced permeability which is essential both in vitro and in vivo. Finally,
      this review highlights the elegant use of honeycomb films as drug-eluting
      biomaterials or as reservoirs for distinct drug delivery systems. STATEMENT OF
      SIGNIFICANCE: Combining biocompatible surfaces and 3D nano/microscale
      topographies, such as pores or grooves, is an effective strategy for
      manufacturing tissue engineering scaffolds. The breath figure (BF) method is an
      easy technique to prepare cell culture substrates with an organized, honeycomb
      like porous surface. These surface features make these scaffolds valuable for
      studying how the cells interact with the biomaterials. Their unique surface
      topography can also resemble the natural environment of the tissues in the human
      body. For that reason, numerous studies, using different cell types, have shown
      that honeycomb films can constitute high performance substrates for cell culture.
      Here, we review those studies, we highlight the advantages of honeycomb films in
      tissue engineering and we discuss their potential as unique drug-eluting systems.

PMID- 29183848
TI  - Combinational siRNA delivery using hyaluronic acid modified amphiphilic
      polyplexes against cell cycle and phosphatase proteins to inhibit growth and
      migration of triple-negative breast cancer cells.
AB  - : Triple-negative breast cancer is an aggressive form of breast cancer with few
      therapeutic options if it recurs after adjuvant chemotherapy. RNA interference
      could be an alternative therapy for metastatic breast cancer, where small
      interfering RNA (siRNA) can silence the expression of aberrant genes critical for
      growth and migration of malignant cells. Here, we formulated a siRNA delivery
      system using lipid-substituted polyethylenimine (PEI) and hyaluronic acid (HA),
      and characterized the size, zeta-potential and cellular uptake of the
      nanoparticulate delivery system. Higher cellular uptake of siRNA by the tailored
      PEI/HA formulation suggested better interaction of complexes with breast cancer
      cells due to improved physicochemical characteristics of carrier and HA-binding
      CD44 receptors. The siRNAs against specific phosphatases that inhibited migration
      of MDA-MB-231 cells were then identified using library screen against 267 protein
      tyrosine phosphatases, and siRNAs to inhibit cell migration were further
      validated. We then assessed the combinational delivery of a siRNA against CDC20
      to decrease cell growth and a siRNA against several phosphatases shown to
      decrease migration of breast cancer cells. Combinational siRNA therapy against
      CDC20 and identified phosphatases PPP1R7, PTPN1, PTPN22, LHPP, PPP1R12A and DUPD1
      successfully inhibited cell growth and migration, respectively, without
      interfering the functional effect of the co-delivered siRNA. The identified
      phosphatases could serve as potential targets to inhibit migration of highly
      aggressive metastatic breast cancer cells. Combinational siRNA delivery against
      cell cycle and phosphatases could be a promising strategy to inhibit both growth
      and migration of metastatic breast cancer cells, and potentially other types of
      metastatic cancer. STATEMENT OF SIGNIFICANCE: The manuscript investigated the
      efficacy of a tailored polymeric siRNA delivery system formulation as well as
      combinational siRNA therapy in metastatic breast cancer cells to inhibit
      malignant cell growth and migration. The siRNA delivery was undertaken by non
      viral means with PEI/HA. We identified six phosphatases that could be critical
      targets to inhibit migration of highly aggressive metastatic breast cancer cells.
      We further report on specifically targeting cell cycle and phosphatase proteins
      to decrease both malignant cell growth and migration simultaneously. Clinical
      gene therapy against metastatic breast cancer with effective and safe delivery
      systems is urgently needed to realize the potential of molecular medicine in this
      deadly disease and our studies in this manuscript is intended to facilitate this
      endeavor.

PMID- 29183849
TI  - A sterilization method for decellularized xenogeneic cardiovascular scaffolds.
AB  - : Decellularized xenogeneic scaffolds have shown promise to be employed as
      compatible and functional cardiovascular biomaterials. However, one of the main
      barriers to their clinical exploitation is the lack of appropriate sterilization
      procedures. This study investigated the efficiency of a two-step sterilization
      method, antibiotics/antimycotic (AA) cocktail and peracetic acid (PAA), on
      porcine and bovine decellularized pericardium. In order to assess the efficiency
      of the method, a sterilization assessment protocol was specifically designed,
      comprising: i) controlled contamination with a known amount of bacteria; ii)
      sterility test; iii) identification of contaminants through MALDI-TOF (Matrix
      Assisted Laser Desorption/Ionization Time-of-Flight) mass spectrometry and iv)
      quantification by the Most Probable Number (MPN) method. This sterilization
      assessment protocol proved to be a successful tool to monitor and optimize the
      proposed sterilization method. The treatment with AA + PAA method provided
      sterile scaffolds while preserving the structural integrity and biocompatibility
      of the decellularized porcine and bovine tissues. However, surface properties and
      cellular adhesion resulted slightly impaired on porcine pericardium. This work
      developed a sterilization method suitable for decellularized pericardial
      scaffolds that could be adopted for in vivo tissue engineering. Together with the
      proposed sterilization assessment protocol, this decontamination method will
      foster the clinical translation of decellularized xenogeneic substitutes.
      STATEMENT OF SIGNIFICANCE: Clinical application of functional and compatible
      xenogeneic decellularized scaffolds has been delayed due to the lack of
      appropriate sterilization methodologies. In this study, it was investigated an
      effective sterilization method optimized for porcine and bovine decellularized
      pericardia, based on the use of antibiotics/antimycotics followed by peracetic
      acid treatment. This treatment effectively sterilizes both species scaffolds,
      proves to maintain tissue overall structure and components, preserves
      biocompatibility and biomechanical properties. Furthermore, it was also developed
      a sterilization assessment protocol used to monitor and validate the previous
      method, consisting in three main parts: i) controlled contamination; ii)
      sterility test, and iii) identification and quantification of contaminants. Both
      methodologies were optimized for the tissues in study but can be applied to other
      scaffolds and accelerate their clinical translation.

PMID- 29183850
TI  - Effects of nanofeatures induced by severe shot peening (SSP) on mechanical,
      corrosion and cytocompatibility properties of magnesium alloy AZ31.
AB  - : The application of biodegradable magnesium-based materials in the biomedical
      field is highly restricted by their low fatigue strength and high corrosion rate
      in biological environments. Herein, we treated the surface of a biocompatible
      magnesium alloy AZ31 by severe shot peening in order to evaluate the potential of
      surface grain refinement to enhance this alloy's functionality in a biological
      environment. The AZ31 samples were studied in terms of micro/nanostructural,
      mechanical, and chemical characteristics in addition to cytocompatibility
      properties. The evolution of surface grain structure and surface morphology were
      investigated using optical, scanning and transmission electron microscopy.
      Surface roughness, wettability, and chemical composition, as well as in depth
      microhardness and residual stress distribution, fatigue behaviour and corrosion
      resistance were investigated. Cytocompatibility tests with osteoblasts (bone
      forming cells) were performed using sample extracts. The results revealed for the
      first time that severe shot peening can significantly enhance mechanical
      properties of AZ31 without causing adverse effects on the growth of surrounding
      osteoblasts. The corrosion behavior, on the other hand, was not improved;
      nevertheless, removing the rough surface layer with a high density of
      crystallographic lattice defects, without removing the entire nanocrystallized
      layer, provided a good potential for improving corrosion characteristics after
      severe shot peening and thus, this method should be studied for a wide range of
      orthopedic applications in which biodegradable magnesium is used. STATEMENT OF
      SIGNIFICANCE: A major challenge for most commonly used metals for bio-implants is
      their non-biodegradability that necessitates revision surgery for implant
      retrieval when used as fixation plates, screws, etc. Magnesium is reported among
      the most biocompatible metals that resorb over time without adverse tissue
      reactions and is indispensable for many biochemical processes in human body.
      However, fast and uncontrolled degradation of magnesium alloys in the
      physiological environment in addition to their inadequate mechanical properties
      especially under repeated loading have limited their application in the
      biomedical field. The present study providesdata on the effect of a relatively
      simple surface nanocrystallziation method with high potential to tailor the
      mechanical and chemical behavior of magnesium based material while maintaining
      its cytocompatibility.

PMID- 29183851
TI  - A retrospective study of human cystic echinococcosis in Basrah province, Iraq.
AB  - Human cystic echinococcosis (CE) is a parasitic zoonosis with serious clinical
      burden and constitutes a challenge to public health in endemic areas worldwide.
      We performed a retrospective study to investigate the occurrence of CE in
      patients at six hospitals in Basrah province, Iraq. In the current study setting,
      data retrieval and validation of the quality of hospital records was very
      challenging considering the difficult situation Iraq is unfortunately facing.
      Hospitalization records were reviewed from January 2005 to December 2015. A total
      of 748 cases of human with CE were diagnosed and operated in Basrah hospitals,
      equivalent to an annual clinical incidence of approximately 4.5 cases per 100 000
      people. Hospital records show that, cystic echinococcosis affected more females
      (61.2%) than males (38.8%). Descriptive review of recorded CE cases in the
      surveyed hospitals revealed that more cases were reported in the age group of 21
      30 years than in the other age groups. Based on the reviewed recorded clinical
      reports, cysts were mainly found in the liver (46.3%) and lungs (28.1%) of the
      patients. Hospital reports demonstrate that females had more hepatic cysts
      (63.9%) than males (36.1%). This study found that CE continues to pose a threat
      to public health in Basrah, and there is a need for more epidemiological
      investigations of CE in humans in order to determine risk factors and the
      economic impact of the disease in this province of Iraq.

PMID- 29183852
TI  - Identification of an area predominantly endemic for childhood and adolescent
      visceral leishmaniasis in central Sudan.
AB  - Although widely spread throughout Sudan, visceral leishmaniasis (VL) is
      predominantly endemic in the Gedaref, southern Blue-Nile, and Umrimta areas
      located in the eastern, southern, and central regions, respectively. Regardless
      of form (endemic or epidemic), VL occurrence follows similar patterns as all ages
      and both sexes are affected. From January 2005 to May 2016, we received a total
      of 563 patients with high suspicion for VL from various endemic areas; 159 were
      children and adolescents (0.5-18 years) from Umrimta (central Sudan). A
      significant observation during this 11-year period of uninterrupted monitoring
      using a standard liquid direct agglutination test (LQ-DAT) version was the
      exclusive VL occurrence (100%) in the child and adolescent populations of Umrimta
      when compared with other endemic areas (27.3%-48.0%). Among 12 child and
      adolescent suspects who initially tested marginal in the standard LQ-DAT, 6
      scored unequivocally positive readings both in an improved LQ-DAT version (based
      on an autochthonous Leishmania donovani strain) and rK28 VL reference test. None
      of the 4 (2.5%) VL adult suspects (>=19years) referred had positive outcomes in
      the improved LQ-DAT version or the VL reference freeze-dried direct agglutination
      and rK28 tests. Further incorporation of antigens derived from autochthonous L.
      donovani strains from Umrimta (central Sudan) or Gedaref (eastern Sudan) in LQ
      DAT significantly increased the agglutination titer levels in the respective VL
      homologous sera (p=0.0263 T=505 and p=0.2814T=219), suggesting possible antigenic
      variation within the predominant Sudanese L. donovani complex. Additional
      research is required to determine characteristics other than the serologically
      based ones reported for the L. donovani strain involved.

PMID- 29183853
TI  - Toxicity of Usnic Acid from Cladonia substellata (Lichen) to embryos and adults
      of Biomphalaria glabrata.
AB  - This study reports the molluscicidal activity of usnic acid isolated from
      Cladonia substellata Vanio (lichen) on embryos at various stages of development
      and in adult mollusks of Biomphalaria glabrata. The toxicity of usnic acid was
      also evaluated through Artemia salina larvae mortality. Usnic acid was extracted
      with diethyl ether, isolated, purified, and its structure confirmed by analyzing
      the spectra of proton nuclear magnetic resonance. LC90 for 24 h of exposure were
      1.62, 4.45, 5.36, and 4.49 MUg mL-1 for blastula, gastrula, trocophore, and
      veliger embryonic stages, respectively, and 3.45 MUg mL-1 for adult snails; LC50
      of usnic acid against A. salina was 2.46 MUg mL-1. LC90 assessed 7 days after
      exposure was 2.56 MUg mL-1 for adult mollusks. In conclusion, these findings
      demonstrate that under laboratory conditions usnic acid has teratogenic and
      molluscicide potential to control the aquatic snail B. glabrata and may prove to
      be a promising candidate in the search for new molluscicide agents, but further
      detailed studies on its molluscicidal effect and possible environmental effects
      are needed.

PMID- 29183854
TI  - Serine 51 residue of Citrobacter freundii tyrosine phenol-lyase assists in C
      alpha-proton abstraction and transfer in the reaction with substrate.
AB  - In the spatial structure of tyrosine phenol-lyase, the Ser51 residue is located
      in the active site of the enzyme. The replacement of Ser51 with Ala by site
      directed mutagenesis led to a decrease of the kcat/Km parameter for reactions
      with l-tyrosine and 3-fluoro-l-tyrosine by three orders of magnitude, compared to
      wild type enzyme. For the elimination reactions of S-alkylcysteines, the values
      of kcat/Km decreased by an average of two orders of magnitude. The results of
      spectral studies of the mutant enzyme gave evidence for a considerable change of
      the chiral properties of the active site as a result of the replacement. Fast
      kinetic studies for the complexes of the mutant form with competitive inhibitors
      allowed us to conclude that the Ser51 residue interacts with the side chain amino
      group of Lys257 at the stage of C-alpha-proton abstraction. This interaction
      ensures the correct orientation of the side chain of Lys257 accepting the C-alpha
      proton of the external aldimine and stabilizes its ammonium form. Also, it is
      probable that Ser51 takes part in formation of a chain of hydrogen bonds which is
      necessary to perform the transfer of the C-alpha-proton to the C-4'-position of
      the leaving phenol group in the reaction with the natural substrate.

PMID- 29183855
TI  - PET/CT imaging of 3D printed devices in the gastrointestinal tract of rodents.
AB  - Fused deposition modelling (FDM) 3D printing (3DP) is a revolutionary technology
      with the potential to transform drug product design in both the pre-clinical and
      clinical arena. The objective of this pilot study was to explore the intestinal
      behaviour of four different polymer-based devices fabricated using FDM 3DP
      technology in rats. Small capsular devices of 8.6 mm in length and 2.65 mm in
      diameter were printed from polyvinyl alcohol-polyethylene glycol graft-copolymer
      (PVA-PEG copolymer, Kollicoat IR), hydroxypropylcellulose (HPC, Klucel),
      ethylcellulose (EC, Aqualon N7) and hypromellose acetate succinate (HPMCAS,
      Aquasolve-LG). A smaller sized device, 3.2 mm in length and 2.65 mm in diameter,
      was also prepared with HPMCAS to evaluate the cut off size of gastric emptying of
      solid formulations in rats. The devices were radiolabelled with
      Fluorodeoxyglucose (18F-FDG) and small animal positron emission
      tomography/computed tomography (microPET/CT) was used to track the movement and
      disintegration of the fabricated devices in the rats. The PVA-PEG copolymer and
      HPC devices disintegrated after 60min following oral administration. The EC
      structures did not disintegrate in the gastrointestinal tracts of the rats,
      whereas the HPMCAS-based systems disintegrated after 420 min. Interestingly, it
      was noted that the devices which remained intact over the course of the study had
      not emptied from the stomach of the rats. This was also the case with the smaller
      sized device. In summary, we report for the first time, the use of a microPET/CT
      imaging technique to evaluate the in vivo behaviour of 3D printed formulations.
      The manipulation of the 3D printed device design could be used to fabricate
      dosage forms of varying sizes and geometries with better gastric emptying
      characteristics suitable for rodent administration. The increased understanding
      of the capabilities of 3DP in dosage form design could, henceforth, accelerate
      pre-clinical testing of new drug candidates in animal models.

PMID- 29183856
TI  - Mesoporous systems for poorly soluble drugs - recent trends.
AB  - When poor aqueous solubility of active pharmaceutical ingredients is encountered
      during a drug formulation process, the toolbox typically utilized contains
      pharmaceutical salts, co-crystals, solid dispersions, cyclodextrins, lipids,
      liposomes and nanocrystals etc. Especially in the pharmaceutical industry, the
      option which confers the greatest benefit with the lowest risk is usually chosen.
      Several factors affect the final decision, but new technologies should also be
      considered especially if they can address several issues at the same time.
      Mesoporous inorganic systems are emerging technologies which can be utilized for
      improving the dissolution of poorly soluble drugs. The number of the scientific
      papers in this field is steadily increasing and the focus of the studies is
      moving away from in vitro to in vivo experiments with the first human trial
      already completed. Meanwhile, several start-up companies focusing on mesoporous
      carriers have been established. Therefore, it is conceivable that the first
      commercial products will find their way to pharmacies during the next 5-10 years.
      The present review surveys recent progress in research on mesoporous materials as
      carriers of poorly soluble drugs. We will concentrate on the research published
      since our previous review published in 2012 [10.1016/j.ijpharm.2012.09.008] up to
      the present day.

PMID- 29183857
TI  - Understanding the generation and maintenance of supersaturation during the
      dissolution of amorphous solid dispersions using modulated DSC and 1H NMR.
AB  - In this study, the dissolution behaviour of dipyridamole (DPM) and cinnarizine
      (CNZ) spray-dried amorphous solid dispersions (ASDs) using polyvinyl pyrrolidone
      (PVP) and polyacrylic acid (PAA) as a carrier matrix were evaluated and compared.
      The drug concentrations achieved from the dissolution of PVP and PAA solid
      dispersions were significantly greater than the equilibrium solubility of
      crystalline DPM and CNZ in phosphate buffer pH 6.8 (PBS 6.8). The maximum drug
      concentration achieved by dissolution of PVP and PAA solid dispersions did not
      exceed the theoretically calculated apparent solubility of amorphous DPM and CNZ.
      However, the degree of supersaturation of DPM and CNZ increased considerably as
      the polymer weight fraction within the solid dispersion increased. In addition,
      the supersaturation profile of DPM and CNZ were studied in the presence and
      absence of the polymers. PAA was found to maintain a higher level of
      supersaturation compared to PVP. The enhanced drug solution concentration
      following dissolution of ASDs can be attributed to the reduced crystal growth
      rates of DPM and CNZ at an equivalent supersaturation. We have also shown that,
      for drugs having high crystallization tendency and weak drug-polymer interaction,
      the feasible way to increase dissolution might be increase the polymer weight
      fraction in the ASD. Solution 1H NMR spectra were used to understand dissolution
      mechanism and to identify drug-polymer interaction. The change in electron
      densities of proton attached to different groups in DPM and CNZ suggested drug
      polymer interaction in solution. The relative intensities of peak shift and
      nature of interaction between drug and polymer in different systems are
      different. These different effects suggest that DPM and CNZ interacts in a
      different way with PVP and PAA in solution which goes some way towards explaining
      the different polymeric effect, particularly in terms of inhibition of drug
      recrystallization and dissolution of DPM and CNZ ASDs. These results established
      that the different drug/polymer interactions in the solid state and in solution
      give rise to the variation in dissolution profile observed for different systems.

PMID- 29183858
TI  - QR encoded smart oral dosage forms by inkjet printing.
AB  - The use of inkjet printing (IJP) technology enables the flexible manufacturing of
      personalized medicine with the doses tailored for each patient. In this study we
      demonstrate, for the first time, the applicability of IJP in the production of
      edible dosage forms in the pattern of a quick response (QR) code. This printed
      pattern contains the drug itself and encoded information relevant to the patient
      and/or healthcare professionals. IJP of the active pharmaceutical ingredient
      (API)-containing ink in the pattern of QR code was performed onto a newly
      developed porous and flexible, but mechanically stable substrate with a good
      absorption capacity. The printing did not affect the mechanical properties of the
      substrate. The actual drug content of the printed dosage forms was in accordance
      with the encoded drug content. The QR encoded dosage forms had a good print
      definition without significant edge bleeding. They were readable by a smartphone
      even after storage in harsh conditions. This approach of efficient data
      incorporation and data storage combined with the use of smart devices can lead to
      safer and more patient-friendly drug products in the future.

PMID- 29183859
TI  - Risk of autism spectrum disorder in children born to mothers with systemic lupus
      erythematosus and rheumatoid arthritis in Taiwan.
AB  - OBJECTIVES: To determine whether offspring of Taiwanese mothers with systemic
      lupus erythematosus or rheumatoid arthritis have a higher risk of autism spectrum
      disorder. METHODS: Using the National Health Insurance database and National
      Birth Registry, we identified a cohort of all live births in Taiwan between 2001
      and 2012. Children born to mothers with systemic lupus erythematosus or
      rheumatoid arthritis were identified and matched with up to 8 controls by
      maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex
      of the child, gestational age, birth weight and place of residence. Marginal Cox
      proportional hazard models were used to estimate relative risk (RR) with 95%
      confidence intervals (CI) for ASD in offspring. RESULTS: Of 1,893,244 newborns,
      0.08% (n=1594) were born to systemic lupus erythematosus mothers, and 0.04%
      (n=673) were born to rheumatoid arthritis mothers. Overall, 5 of 673 (0.74%)
      offspring of rheumatoid arthritis mothers, 7 of 1594 (0.44%) offspring of
      systemic lupus erythematosus mothers and 10,631 of 1,893,244 (0.56%) offspring of
      all mothers developed autism spectrum disorder. Autism spectrum disorder
      incidence (per 100,000 person-years) was 140.39 (95% CI, 45.58-327.62) for the
      rheumatoid arthritis group and 76.19 (95% CI, 30.63-156.97) for the systemic
      lupus erythematosus group. Autism spectrum disorder risk was not significantly
      higher for children born to mothers with rheumatoid arthritis (HR, 1.42; 95% CI,
      0.60-3.40) or systemic lupus erythematosus (HR, 0.76; 95% CI, 0.36-1.59).
      CONCLUSIONS: Children born to women with systemic lupus erythematosus or
      rheumatoid arthritis do not have a higher risk of autism spectrum disorder.

PMID- 29183860
TI  - Anti-citrullinated peptides antibodies in systemic sclerosis: Meta-analysis of
      frequency and meaning.
AB  - OBJECTIVES: Diagnosis of systemic sclerosis (SSc) is partially determined by the
      presence of specific autoantibodies often associated with specific clinical
      features. Recent studies report the presence of ACPA in SSc. We aimed to evaluate
      the prevalence of ACPA in SSc and to assess their influence on clinical
      presentation of SSc. METHODS: A systematic literature search was performed using
      PubMed and Cochrane databases' publications between 1999 and March 2017. Search
      terms were: "systemic sclerosis [MeSH] AND (ACPA OR anti-CCP OR rheumatoid factor
      OR cohort OR value diagnostic)". In a first step, we selected cohorts with >50
      SSc patients with ACPA identification, for ACPA frequency determination. In a
      second step, we included studies that analysed clinical profiles according to
      ACPA status. Meta-analyses were performed when at least two studies were
      available. RESULTS: First, we identified 13 observational studies with a total of
      1231 SSc patients. The mean prevalence of ACPA in SSc was 9.2%. Secondly, we
      identified nine studies reporting clinical aspects according to ACPA status. Our
      meta-analyses showed a significant association between ACPA positivity and the
      presence of arthritis (odds ratio (OR)=22.48 [10.71-47.21]), joint erosions seen
      on X-rays (OR=14.79 [6.38-34.28]), pulmonary fibrosis (OR=2.75 [1.21-6.24]),
      oesophagus involvement (OR=2.72 [1.05-7.07]), and diffuse skin involvement
      (OR=2.21 [1.21-4.03]). CONCLUSIONS: The prevalence of ACPA in scleroderma is
      9.2%. Our meta-analysis shows an increased risk for erosive arthritis, pulmonary
      fibrosis, oesophagus involvement and diffuse skin involvement, in patients with
      ACPA-positive SSc. ACPA should be systematically included in SSc assessment.

PMID- 29183861
TI  - Bilateral striopallidodentate calcinosis associated with Sjogren's syndrome and
      IgDlambda monoclonal gammopathy of undetermined significance.
AB  - We presented the first case of bilateral striopallidodentate calcinosis secondary
      to Sjogren's syndrome. Further consideration should be given to the association
      between Sjogren's syndrome and bilateral striopallidodentate calcinosis, because
      Sjogren's syndrome is latent, but more frequent than other autoimmune diseases.

PMID- 29183863
TI  - A new strategy for battling bacterial resistance: Turning potent, non-selective
      and potentially non-resistance-inducing biocides into selective ones.
AB  - Antibiotic alternatives are in great need for combating antibiotic resistance.
      Selective delivery of a potent non-selective non-resistance-inducing biocide
      (C17) to MRSA was achieved by encapsulating it in solid lipid nanoparticles
      (SLNs) conjugated with a MRSA-specific antibody (termed as "Ab"). The C17-loaded
      Ab-conjugated SLNs (C17-SLN-Ab) demonstrated significantly better antimicrobial
      activity than its antibody free counterpart (C17-loaded SLN) and C17-loaded SLN
      with a non-specific IgG antibody. In a new MRSA/fibroblast co-culture assay, C17
      SLN-Ab showed selective toxicity toward MRSA than fibroblast cells. C17-SLN-Ab
      possesses double selectivity, exhibiting higher toxicity to MRSA than to
      Pseudomonas aeruginosa. This same strategy was used to successfully increase
      C17's selectivity against E. coli K12 by switching the conjugated anti-MRSA
      antibody to an anti-E. coli antibody, demonstrating versatility of this new
      strategy. This proof-of-concept research can be extended to other non-selective
      antimicrobials, against which bacterial resistance is unlikely to develop, to
      generate a new group of promising antibiotic alternatives.

PMID- 29183862
TI  - The association of ERAP1 and ERAP2 single nucleotide polymorphisms and their
      haplotypes with psoriasis vulgaris is dependent on the presence or absence of the
      HLA-C*06:02 allele and age at disease onset.
AB  - The aim of this case-control study was to elucidate the role of some single
      nucleotide polymorphisms (SNPs) in the ERAP1 (rs27524, rs27044, rs30187,
      rs2287987 and rs26653) and ERAP2 (rs2248374) genes in predicting the risk for
      psoriasis vulgaris in the Polish population. ERAP1, ERAP2 and HLA-C*06:02 typing
      was done using the TaqMan SNP genotyping assays. We confirmed a strong
      association of the HLA-C*06:02 allele with early-onset psoriasis. In ERAP1,
      rs30187T increased the risk of psoriasis in HLA-C*06:02-positive patients, most
      strongly in late onset psoriasis, whereas it was protective when the HLA-C*06:02
      allele was absent. We also found a protective effect of the ERAP2 rs2248374A
      allele and rs2248374AA genotype only in HLA-C*06:02 carriers, especially in the
      subgroup of patients with juvenile psoriasis. Analysis of combined haplotypes for
      ERAP1 and ERAP2 also revealed differences when the patients and controls were
      stratified by HLA-C*06:02. An ERAP1 haplotype known to possess high enzymatic
      activity was associated with psoriasis if HLA-C*06:02 was present and a
      functional ERAP2 allele was absent. In the absence of HLA-C*06:02, an ERAP1
      haplotype of low activity was conducive to psoriasis if a functional ERAP2 allele
      was present, but the same ERAP1 haplotype was protective if the ERAP2 allele was
      defective.

PMID- 29183864
TI  - Surgery for Recurrent High-Grade Glioma After Treatment with Bevacizumab.
AB  - BACKGROUND: Bevacizumab (BVZ) is an antiangiogenic agent approved by the Food and
      Drug Administration that is used for the treatment of recurrent glioblastoma.
      Complications related to impaired healing may adversely affect patients resected
      for recurrent high-grade glioma (HGG) after treatment with BVZ. OBJECTIVE: To
      examine the complication rate, outcome, and tumor vasculature in patients
      resected for recurrent HGG after treatment with BVZ. METHODS: Data were reviewed
      retrospectively from patients undergoing surgery for recurrent HGG after
      treatment with BVZ. Results were compared with a control group of recurrently
      operated BVZ-naive HGG. Tumor samples and magnetic resonance imaging scans were
      analyzed. RESULTS: Fifteen patients underwent HGG resection after progression
      after BVZ. Forty-four BVZ-naive patients who underwent surgeries for tumor
      recurrence were included as controls. Median time from BVZ treatment to surgery
      was 30 days (2-107). Median overall survival from time of tumor diagnosis was
      21.0 months (12-83.0), and median survival from post-BVZ surgery was 5.0 months
      (2.0-19.0), compared with 8.1 months in BVZ-naive controls measured from time of
      their last reoperation. Five of the 15 patients survived 6 or more months after
      post-BVZ surgery. Nine patients developed postsurgical complications requiring
      intervention. Complication rates for surgery after BVZ treatment were 66.7%
      compared with 38.6% in the control group (P = 0.077). We did not see overt
      changes in histopathology or immunohistochemistry staining; however, tumor
      vasculature in tumors resected after treatment with BVZ showed a significant
      decrease in mean vessel density. CONCLUSIONS: Surgery for recurrent HGG may be
      feasible in a select group of patients. Mean tumor vessel density may be
      decreased after treatment with BVZ.

PMID- 29183865
TI  - Intraventricular Glioblastoma Multiforme in A Child with L2-Hydroxyglutaric
      Aciduria.
AB  - L2-hydroxyglutaric aciduria (L2-HGA) is a rare neurometabolic disease
      characterized by accumulation of L2-hydroxyglutarate (L2-HG), a potential
      oncometabolite resulting in significant lifetime risk for cerebral tumors.
      Herein, we present a case of intraventricular glioblastoma multiforme (GBM) in a
      16-year-old child with L2-HGA who presented with rapid functional decline and
      persistent vomiting. The tumor was completely resected, and the patient remained
      well at 2-year follow-up. Clinicians should be aware of the usual insidious
      nature of the disease. Rapid deterioration is unusual and should raise the
      suspicion of tumor development. This case also illustrates the importance of
      surveillance neuroimaging in patients with L2-HGA. To the best of our knowledge,
      only 1 case of GBM has been reported and it was sited in the temporal lobe,
      unlike the unusual intraventricular location in our case.

PMID- 29183866
TI  - An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4
      and AIM2 inflammasomes.
AB  - The proinflammatory protease caspase-1 plays pivotal roles in central pathways of
      innate immunity, thereby contributing to pathogen clearance. Beside its
      physiological role, dysregulated activity of caspase-1 is known to contribute to
      an increasing number of diseases. In this study, we optimized and validated a low
      volume human whole blood assay facilitating the measurement of caspase-1
      activation and inflammasome-related gene expression upon stimulation of the
      NLRP3, NLRC4 or AIM2 inflammasome. Using the NLRP3 inflammasome specific
      inhibitor MCC950, we were able to measure the activity of canonical or
      alternative NLRP3 pathways, AIM2 and NLRC4 inflammasomes in whole blood. Based on
      our data we assume a superposition of NLRP3 and NLRC4 inflammasome activities in
      human whole blood following stimulation with S. typhimurium. The optimized whole
      blood assay may be suitable for diagnostic and research purposes for pediatric
      patients who can only donate small amounts of blood.

PMID- 29183867
TI  - The epidermal growth factor receptor inhibitor AG1478 inhibits eosinophilic
      inflammation in upper airways.
AB  - Mucus hypersecretion and eosinophil infiltration are important characteristics of
      eosinophilic inflammation in upper airways, such as allergic rhinitis and chronic
      rhinosinusitis with nasal polyp. EGFR transactivation induces mucus and
      inflammatory cytokine secretion from airway epithelial cells. However, the roles
      of EGFR in eosinophilic inflammation in upper airways are still unknown. The
      purpose of the study is to elucidate the effects of the EGFR inhibitor AG1478 on
      eosinophilic airway inflammation. AG1478 significantly inhibited thrombin-induced
      GM-CSF secretion from nasal epithelial cells and thrombin-induced secretion of
      eotaxin-1 and RANTES from nasal fibroblasts. Intranasal instillation of AG1478
      inhibited OVA-induced goblet cell metaplasia, mucus production and
      eosinophil/neutrophil infiltration in rat nasal epithelium, as did
      intraperitoneal injection of AG1478. These results indicate that EGFR
      transactivation plays an important role in eosinophilic airway inflammation.
      Intranasal instillation of an EGFR inhibitor may be a new therapeutic approach
      for the treatment of intractable eosinophilic inflammation in upper airways.

PMID- 29183868
TI  - Providing Home-Based HIV Testing and Counseling for Transgender Youth (Project
      Moxie): Protocol for a Pilot Randomized Controlled Trial.
AB  - BACKGROUND: Transgender and gender nonconforming people experience some of the
      highest human immunodeficiency virus (HIV) rates in the United States, and
      experience many structural and behavioral barriers that may limit their
      engagement in HIV testing, prevention, and care. Evidence suggests that
      transgender and gender nonconforming youth (TY) are especially vulnerable to
      acquiring HIV, yet there is little research on TY and few services are targeted
      towards HIV testing, prevention, and care for this population. Telehealth
      presents an opportunity to mitigate some structural barriers that TY experience
      in accessing HIV testing, allowing TY to engage in HIV testing and counseling in
      a safe and nonjudgmental space of their choosing. Project Moxie is an HIV
      prevention intervention that pairs the use of HIV self-testing with remote video
      based counseling and support from a trained, gender-affirming counselor. This
      study aims to offer a more positive HIV testing and counseling experience, with
      the goal of improving HIV testing frequency. OBJECTIVE: Project Moxie involves a
      pilot randomized controlled trial (RCT) of 200 TY aged 15-24 years, who are
      randomized on a 1:1 basis to control or intervention arms. The aim is to examine
      whether the addition of counseling provided via telehealth, coupled with home
      based HIV testing, can create gains in routine HIV testing among TY over a six
      month follow-up period. METHODS: This study implements a prospective pilot RCT of
      200 TY recruited online. Participants in the control arm will receive one HIV
      self-testing kit and will be asked to report their results via the study's
      website. Participants in the experimental arm will receive one HIV self-testing
      kit and will test with a remotely-located counselor during a prescheduled video
      counseling session. Participants are assessed at baseline, and at three and six
      months posttesting. RESULTS: Project Moxie was launched in June 2017 and
      recruitment is ongoing. As of August 21, 2017, the study had enrolled 130
      eligible participants. CONCLUSIONS: Combining home-based HIV testing and video
      based counseling allows TY, an often stigmatized and marginalized population, to
      test for HIV in a safe and nonjudgmental setting of their choosing. This approach
      creates an opportunity to reduce the high rate of HIV among TY through engagement
      in care, support, and linkage to the HIV treatment cascade for those who test
      positive. TRIAL REGISTRATION: ClinicalTrials.gov NCT03185975;
      https://clinicaltrials.gov/ct2/show/NCT03185975 (Archived by WebCite at
      http://www.webcitation.org/6vIjHJ93s).

PMID- 29183869
TI  - Detecting Acute Otitis Media Symptom Episodes Using a Mobile App: Cohort Study.
AB  - BACKGROUND: Population cohort studies are useful to study infectious diseases
      episodes not attended by health care services, but conventional paper diaries and
      questionnaires to capture cases are prone to noncompliance and recall bias. Use
      of smart technology in this setting may improve case finding. OBJECTIVE: The
      objective of our study was to validate an interactive mobile app for monitoring
      occurrence of acute infectious diseases episodes in individuals, independent of
      health care seeking, using acute otitis media (AOM) symptom episodes in infants
      as a case study. We were interested in determining participant compliance and app
      performance in detecting and ascertaining (parent-reported) AOM symptom episodes
      with this novel tool compared with traditional methods used for monitoring study
      participants. METHODS: We tested the InfectieApp research app to detect AOM
      symptom episodes. In 2013, we followed 155 children aged 0 to 3 years for 4
      months. Parents recorded the presence of AOM symptoms in a paper diary for 4
      consecutive months and completed additional disease questionnaires when AOM
      symptoms were present. In 2015 in a similar cohort of 69 children, parents used
      an AOM diary and questionnaire app instead. RESULTS: During conventional and app
      based recording, 93.13% (17,244/18,516) and 94.56% (7438/7866) of symptom diaries
      were returned, respectively, and at least one symptom was recorded for 32.50%
      (n=5606) and 43.99% (n=3272) of diary days (P<.01). The incidence of AOM symptom
      episodes was 605 and 835 per 1000 child-years, respectively. Disease
      questionnaires were completed for 59% (17/29) of episodes when participants were
      using conventional recording, compared with 100% (18/18) for app-based recording.
      CONCLUSIONS: The use of the study's smart diary app improved AOM case finding and
      disease questionnaire completeness. For common infectious diseases that often
      remain undetected by health care services, use of this technology can
      substantially improve the accurateness of disease burden estimates.

PMID- 29183870
TI  - Online Self-Management Support for Family Caregivers to Help Them Manage Behavior
      Changes in Their Relative With Dementia: Study Protocol for a Randomized
      Controlled Trial and a Process Evaluation.
AB  - BACKGROUND: Online interventions are potentially effective ways to support family
      caregivers in the management of behavior changes in their relative with dementia.
      OBJECTIVE: The objective of this paper is to present the design of a study
      evaluating and comparing 3 intervention arms for online self-management support.
      METHODS: A randomized controlled trial (RCT) will be conducted with a total of 81
      family caregivers of community-dwelling people with dementia in the Netherlands.
      Family caregivers will be randomly allocated to one of the following intervention
      arms: (1) a major self-management support intervention consisting of personal
      email contacts with a nurse specialized in dementia care, online videos, and
      electronic bulletins (e-bulletins); (2) a medium self-management support
      intervention consisting of only online videos and e-bulletins; and (3) a minor
      self-management support intervention with only e-bulletins. The primary outcome
      is the self-efficacy of the family caregiver. The secondary outcomes are the
      behavior problems of the person with dementia as reported by the family
      caregiver, and positive and negative aspects of the relationship. Background
      characteristics (eg, type of family relationship) will also be assessed. All data
      for the RCT will be collected via online questionnaires, administered before the
      intervention (T0), after 6 weeks (T1), and after 12 weeks (T2). Alongside the
      RCT, a process evaluation will be conducted, based on a number of evaluation
      questions and semi-open interviews with family caregivers. RESULTS: Data
      collection will be completed in August 2017. Study results will be reported in
      early 2018. CONCLUSIONS: The study will shed more light on the effect of online
      self-management support interventions and insights will be gained into whether a
      major intervention, consisting of personal email contacts with specialized
      nurses, videos, and e-bulletins, has more effect than smaller online
      interventions. This is relevant in an age with increasing numbers of people with
      dementia, growing pressure on family caregivers, more and more people using the
      Internet, and increasing healthcare costs. TRIAL REGISTRATION: Nederlands Trial
      Registry (NTR): NTR6237;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6237 (Archived by
      WebCite at http://www.webcitation.org/6v0S4fxTC).

PMID- 29183873
TI  - Effect of chronic liraglutide therapy and its withdrawal on time to postchallenge
      peak glucose in type 2 diabetes.
AB  - Delayed timing of peak serum glucose following an oral glucose challenge can
      predict declining beta-cell function and worsening glucose tolerance over time.
      Accordingly, postchallenge peak glucose is typically delayed in patients with
      type 2 diabetes (T2DM). However, little is known about the capacity of
      antidiabetic medications to reverse this delay. Thus, we sought to evaluate the
      effect of the glucagon-like peptide-1 agonist liraglutide on time to peak glucose
      in early T2DM. In this secondary analysis of a double-blind placebo-controlled
      trial, 51 patients with T2DM of 2.6 +/- 1.9 yr duration were randomized to daily
      subcutaneous liraglutide or placebo injection for 48 wk, with oral glucose
      tolerance test (OGTT) performed every 12 wk while on therapy and after a 2-wk
      washout. On each OGTT, time to peak glucose was determined from venous glucose
      measurements at 0, 10, 20, 30, 60, 90, and 120 min. At randomization, most
      patients in both arms exhibited peak glucose at 90 min postchallenge. By 12 wk,
      65.4% of the liraglutide arm had shifted to an earlier peak (vs. 36% on placebo;
      P = 0.19), with little change thereafter at 24, 36, and 48 wk. After the 2-wk
      washout, however, 57.7% of those who had been on liraglutide reverted to a later
      peak (vs. 4.5% on placebo; P < 0.001). This shift was associated with declining
      beta-cell function ( P = 0.001), resulting in higher 2-h blood glucose at washout
      in the liraglutide arm compared with placebo ( P = 0.001). Thus, although
      liraglutide possibly might improve the delay in peak glucose, its cessation
      yielded a worsening thereof and higher glycemia. The mechanisms underlying these
      observations and their clinical implications warrant further investigation.

PMID- 29183872
TI  - Endotoxin-initiated inflammation reduces testosterone production in men of
      reproductive age.
AB  - Inflammation, both acute and chronic, is associated with testosterone deficiency,
      raising the possibility of a direct causal link. One potential trigger for
      inflammation in obese men is the passage of intestinal bacteria into the
      circulation due to a breakdown in mucosal barrier integrity. Recently, we
      hypothesized that this endotoxin exposure may cause androgen deficiency in obese
      men. To test this hypothesis, we analyzed the relationship between serum levels
      of lipopolysaccharide-binding protein (LBP), an indirect measure of endotoxin
      exposure, against male reproductive hormones, inflammatory markers (C-reactive
      protein, IL-1beta, IL-6, TNF-alpha), and adiposity in 75 men. Adiposity was
      positively correlated with endotoxin exposure (LBP) and inflammation (C-reactive
      protein, IL-6) and negatively correlated with testosterone. Furthermore,
      endotoxemia (LBP) was negatively correlated with serum testosterone but
      positively correlated with IL-6. Multivariate analysis revealed a significant,
      negative correlation between serum IL-6 and free testosterone. In a second
      interventional study, low-dose endotoxin challenge in lean men produced a
      transient inflammatory response that was followed by a decline in serum
      testosterone, without changes in LH or FSH, providing further evidence that
      endotoxin-driven inflammation may result in impaired Leydig cell function.

PMID- 29183874
TI  - Which anticoagulant for stroke prevention in atrial fibrillation?

PMID- 29183875
TI  - Navigating chronic pain: how taking a few wrong turns can miss sinister
      pathology.
AB  - Bone sarcomas are rare in childhood, and their presentation can often mimic more
      benign complaints or chronic musculoskeletal pain. Ewing sarcomas in particular
      are often diagnosed after a significant delay from the onset of symptoms. At a
      population level, a long diagnostic delay is not necessarily associated with
      worse survival , as tumours that display slow growth also tend to be less
      aggressive. For any specific individual however, a delayed diagnosis can result
      in a larger tumour that is more difficult to treat. We explore a case of Ewing
      sarcoma and discuss how the presenting features, approach to imaging and the role
      of clinician cognitive bias may have led to diagnostic delay.Ewing sarcoma is
      treated with chemotherapy and surgery and/or radiotherapy based on the initial
      site of disease, size of tumour and response to initial treatment. With current
      UK treatments, overall survival is approximately 70% for localised tumours and up
      to 20% in those with metastatic disease. Bone sarcomas usually present with deep
      seated mechanical bone pain akin to toothache. The pain can be intermittent over
      the course of days or weeks, but pain occurring at night should be considered a
      red flag. Swelling may also present. On plain X-ray, bone sarcomas can
      demonstrate areas of bone destruction, new bone formation, periosteal
      inflammation and soft tissue swelling, but in some cases the changes are very
      subtle. Persistent unexplained symptoms require MRI to exclude tumours and detect
      potential benign causes that are amenable to treatment.

PMID- 29183876
TI  - Canadian mother whose son died from strep throat sentenced to three years in
      prison.

PMID- 29183877
TI  - Burnout syndrome among healthcare professionals.

PMID- 29183878
TI  - Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers'
      effectiveness in axial spondyloarthritis: results of a prospective, multicentre
      study.
AB  - OBJECTIVE: To describe the prevalence of fibromyalgia (FM) in an axial
      spondyloarthritis (axSpA) population and to confirm that concomitant FM had a
      negative impact on tumour necrosis factor blockers' (TNFb) response. DESIGN:
      Prospective observational study with two visits 3 months apart. PATIENTS: Adult
      patients with AxSpa initiating a TNFb. STUDY GROUPS: FM was defined by the
      Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained
      positive FiRST (both visits) and by a fulfilment of the 1990 American College of
      Rheumatology criteria for FM. STATISTICAL ANALYSIS: Prevalence of FM; evaluation
      of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors
      known to have an impact on TNFb response. RESULTS: Among the 508 patients
      included in the main analysis, 192 (37.8%) were screened at baseline as FM.
      Percentage of success after 12 weeks of treatment was lower in the FM group for
      most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not
      FM groups according to the FiRST), except for the C reactive protein change
      endpoints which were not different across groups. CONCLUSION: This study confirms
      that FM coexists in patients with axSpA and that its presence seems to have a
      negative impact on TNFb response, which seems more related to the self-reported
      instruments used in its evaluation, rather than a different treatment effect of
      the molecule in this subgroup of patients.

PMID- 29183879
TI  - Admission factors associated with international medical graduate certification
      success: a collaborative retrospective review of postgraduate medical education
      programs in Ontario.
AB  - BACKGROUND: The failure rate on certification examinations of The College of
      Family Physicians of Canada (CFPC) and the Royal College of Physicians and
      Surgeons of Canada (RCPSC) is significantly higher for international medical
      graduates than for Canadian medical school graduates. The purpose of the current
      study was to generate evidence that supports or refutes the validity of
      hypotheses proposed to explain the lower success rates. METHODS: We conducted
      retrospective analyses of admissions and certification data to determine the
      factors associated with success of international medical graduate residents on
      the certification examinations. International medical graduates who entered an
      Ontario residency program between 2005 and 2012 and had written a certification
      examination by the time of the analysis (2015) were included in the study. Data
      available at the time of admission for each resident, including demographic
      characteristics, previous experiences and previous professional experiences, were
      collected from each of the 6 Ontario medical schools and matched with
      certification examination results provided by The CFPC and the RCPSC. We
      developed logistic regression models to determine the association of each factor
      with success on the examinations. RESULTS: Data for 900 residents were analyzed.
      The models revealed resident age to be strongly associated with performance
      across all examinations. Fluency in English, female sex and the Human Development
      Index value associated with the country of medical school training had
      differential associations across the examinations. INTERPRETATION: The findings
      should contribute to an improved understanding of certification success by
      international medical graduates, help residency programs identify at-risk
      residents and underpin the development of specific educational and remedial
      interventions. In considering the results, it should be kept in mind that some
      variables are not amenable to changes in selection criteria.

PMID- 29183880
TI  - Formal carers providing end-of-life care and bereavement support to people with
      intellectual disabilities have unmet learning needs.

PMID- 29183881
TI  - Young people with an intellectual disability experience poorer physical and
      mental health during transition to adulthood.

PMID- 29183882
TI  - Automated telephone communication systems may have the potential to play a
      positive role in healthcare.

PMID- 29183883
TI  - Sixty seconds on . . . potassium.

PMID- 29183884
TI  - NICE to ban mesh for vaginal wall prolapse.

PMID- 29183885
TI  - Can we predict the clinical outcome of arthroscopic partial meniscectomy? A
      systematic review.
AB  - NHS-PROSPERO REGISTRATION NUMBER: 42016048592 OBJECTIVE: In order to make a more
      evidence-based selection of patients who would benefit the most from arthroscopic
      partial meniscectomy (APM), knowledge of prognostic factors is essential. We
      conducted a systematic review of predictors for the clinical outcome following
      APM. DESIGN: Systematic review DATA SOURCES: Medline, Embase, Cochrane Central
      Register, Web of Science, SPORTDiscus, PubMed Publisher, Google Scholar INCLUSION
      CRITERIA: Report an association between factor(s) and clinical outcome; validated
      questionnaire; follow-up >1 year. EXCLUSION CRITERIA: <20 subjects; anterior
      cruciate ligament-deficient patients; discoid menisci; meniscus repair,
      transplantation or implants; total or open meniscectomy. METHODS: One reviewer
      extracted the data, two reviewers assessed the risk of bias and performed a best
      evidence synthesis. RESULTS: Finally, 32 studies met the inclusion criteria.
      Moderate evidence was found, that the presence of radiological knee
      osteoarthritis at baseline and longer duration of symptoms (>1 year) are
      associated with worse clinical outcome following APM. In addition, resecting >50%
      of meniscal tissue and leaving a non-intact meniscal rim after meniscectomy are
      intra-articular predictive factors for worse clinical outcome. Moderate evidence
      was found that sex, onset of symptoms (acute or chronic), tear type or
      preoperative sport level are not predictors for clinical outcome. Conflicting
      evidence was found for the prognostic value of age, perioperative chondral
      damage, body mass index and leg alignment. SUMMARY/CONCLUSION: Long duration of
      symptoms (>1 year), radiological knee osteoarthritis and resecting >50% of
      meniscus are associated with a worse clinical outcome following APM. These
      prognostic factors should be considered in clinical decision making for patients
      with meniscal tears.

PMID- 29183886
TI  - The impact of age, NPM1mut, and FLT3ITD allelic ratio in patients with acute
      myeloid leukemia.

PMID- 29183888
TI  - Histiocytic sarcoma: a population-based analysis of incidence, demographic
      disparities, and long-term outcomes.

PMID- 29183887
TI  - How I manage monoclonal gammopathy of undetermined significance.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is, in many ways, a
      unique hematologic entity. Unlike most hematologic conditions in which the
      diagnosis is intentional and credited to hematologists, the discovery of MGUS is
      most often incidental and made by nonhematologists. MGUS is considered an
      obligate precursor to several lymphoplasmacytic malignancies, including
      immunoglobulin light-chain amyloidosis, multiple myeloma, and Waldenstrom
      macroglobulinemia. Therefore, long-term follow-up is generally recommended.
      Despite its high prevalence, there is surprisingly limited evidence to inform
      best clinical practice both at the time of diagnosis and during follow-up. We
      present 7 vignettes to illustrate common clinical management questions that arise
      during the course of MGUS. Where evidence is present, we provide a concise
      summary of the literature and clear recommendations on management. Where evidence
      is lacking, we describe how we practice and provide a rationale for our approach.
      We also discuss the potential harms associated with MGUS diagnosis, a topic that
      is rarely, if ever, broached between patients and providers, or even considered
      in academic debate.

PMID- 29183889
TI  - Changes in regional body fat, lean body mass and body shape in trans persons
      using cross-sex hormonal therapy: results from a multicenter prospective study.
AB  - OBJECTIVE: Cross-sex hormonal therapy (CHT) in trans persons affects their total
      body fat and total lean body mass. However, it is unknown how separate body
      regions are affected and whether these changes alter body shape. Therefore, the
      aim of this study was to determine the effects on body fat and lean body mass in
      separate body regions and on body shape after one year of CHT. DESIGN AND
      METHODS: In a multicenter prospective study at university hospitals, 179 male-to
      female gender dysphoric persons, referred to as transwomen, and 162 female-to
      male gender dysphoric persons, referred to as transmen, were included. All
      underwent whole-body dual-energy X-ray absorptiometry and anthropometric
      measurements before and after one year of CHT. RESULTS: In transwomen, increases
      in body fat ranged from +18% (95% CI: 13%;23%) in the android region to +42% (95%
      CI: 37%;46%) in the leg region and +34% (95% CI: 29%;38%) in the gynoid region.
      In transmen, changes in body fat ranged from -16% (95% CI: -19;-14%) in the leg
      region and -14% in the gynoid region (95% CI: -16%;-12) to no change in the
      android region (+1%, 95% CI: -3%;5%). Waist-to-hip ratio (WHR) decreased in
      transwomen (-0.03, 95% CI: -0.04;-0.02) mainly due to an increase in hip
      circumference (+3.2 cm, 95% CI: 2.3;4.0). Transmen have a decrease in hip
      circumference (-1.9 cm, 95% CI: -3.1;-0.7) resulting in an increase in WHR
      (+0.01, 95% CI: 0.00;0.02). CONCLUSIONS: CHT causes a more feminine body fat
      distribution and a lower WHR in transwomen and a more masculine body fat
      distribution with a lower hip circumference in transmen.

PMID- 29183890
TI  - Planning Statistical Quality Control to Minimize Patient Risk: It's About Time.

PMID- 29183892
TI  - Treatment of advanced colorectal cancer in a patient with cardiotoxic reactions
      to 5-fluorouracil and capecitabine using suboptimal doses.
AB  - A 32-year-old female with stage IV colorectal cancer and metastasis to the liver
      experienced cardiotoxic reactions after treatment with 5-fluorouracil and its
      oral prodrug capecitabine even at two-thirds the recommended dose. After careful
      considerations, the decision was made to attempt capecitabine retrial at a
      further suboptimal dose with combination chemotherapy where she no longer
      experienced cardiac events. As a result, the liver tumour shrank and rectal mass
      stabilised, tumour markers dropped and she underwent surgical resection of both
      masses. Later there was local recurrence of disease near the previous liver
      tumour, so the suboptimal capecitabine therapy was restarted without complaint.
      The patient became a candidate for a NanoKnife procedure, offering a potentially
      curative therapy. This case report summarises a novel treatment strategy for
      those patients with advanced colorectal cancer who experience cardiotoxic
      reactions to fluoropyrimidines, the active agent of gold standard treatment.

PMID- 29183893
TI  - Brief psychotic episode in a patient with chromosome 2q37 microdeletion syndrome.
AB  - A 21-year-old woman with moderate learning disability secondary to chromosome 2
      microdeletion at q37 was admitted to a general adult psychiatric ward following a
      period of agitation with incessant pressure of speech, nihilistic delusions and
      worsening of sleep and eating patterns. Her presentation was preceded for a
      number of weeks by social stressors of an ill family member and another family
      member moving away. She had also been diagnosed and treated for a respiratory
      infection several weeks prior to presentation. Her presentation improved with low
      dose antipsychotic medication and parallel input from the general adult mental
      health team and the psychiatry of intellectual disability team.

PMID- 29183894
TI  - Dying art of a history and physical: pulsatile tinnitus.
AB  - Modern medicine often leaves the history and physical by the wayside. Physicians
      instead skip directly to diagnostic modalities like MRI and angiography. In this
      case report, we discuss a patient who presented with migraine symptoms.
      Auscultation revealed signs of pulsatile tinnitus. Further imaging concluded that
      it was secondary to a type I dural arteriovenous fistula. Thanks to a proper and
      thorough history and physical, the patient was streamlined into an accurate and
      efficient work-up leading to symptomatic relief and quality of life improvement.
      Imaging is a powerful adjunctive technique in modern medicine, but physicians
      must not rely on machines to diagnose their patients. If this trend continues, it
      will have a tremendous negative impact on the cost and calibre of healthcare. Our
      hope is that this case will spread awareness in the medical community, urging
      physicians to use the lost art of a history and physical.

PMID- 29183891
TI  - TEM8/ANTXR1-Specific CAR T Cells as a Targeted Therapy for Triple-Negative Breast
      Cancer.
AB  - Triple-negative breast cancer (TNBC) is an aggressive disease lacking targeted
      therapy. In this study, we developed a CAR T cell-based immunotherapeutic
      strategy to target TEM8, a marker initially defined on endothelial cells in colon
      tumors that was discovered recently to be upregulated in TNBC. CAR T cells were
      developed that upon specific recognition of TEM8 secreted immunostimulatory
      cytokines and killed tumor endothelial cells as well as TEM8-positive TNBC cells.
      Notably, the TEM8 CAR T cells targeted breast cancer stem-like cells, offsetting
      the formation of mammospheres relative to nontransduced T cells. Adoptive
      transfer of TEM8 CAR T cells induced regression of established, localized patient
      derived xenograft tumors, as well as lung metastatic TNBC cell line-derived
      xenograft tumors, by both killing TEM8+ TNBC tumor cells and targeting the tumor
      endothelium to block tumor neovascularization. Our findings offer a preclinical
      proof of concept for immunotherapeutic targeting of TEM8 as a strategy to treat
      TNBC.Significance: These findings offer a preclinical proof of concept for
      immunotherapeutic targeting of an endothelial antigen that is overexpressed in
      triple-negative breast cancer and the associated tumor vasculature. Cancer Res;
      78(2); 489-500. (c)2017 AACR.

PMID- 29183895
TI  - Rare and unusual case of perforated appendicitis in a Spigelian hernia.

PMID- 29183896
TI  - Paediatric Salter-Harris type IV injury of distal tibia with talus fracture.
AB  - Fracture of talus with Salter-Harris injury of the distal end of tibia is a rare
      injury in paediatric age group. The authors report a case of a 13-year-old male
      child who sustained type IV Salter-Harris injury to the medial malleolus with
      coronal spilt along with spilt and depressed fracture of the neck of talus and
      fracture of the lateral process of talus with stable compression fracture of
      spine sustained due to fall from 6 meters height. CT scan delineated the
      morphology of fracture pattern and helped in preoperative planning. Talar
      articular fracture was reduced and fixed arthroscopically while distal tibial
      fracture was fixed under image intensifier. We observed favourable outcome
      following arthroscopic reduction at 4-year follow-up.

PMID- 29183897
TI  - Puzzling thyroid function test.
AB  - A 13-1/2-year-old boy was referred to the Department of Endocrinology as a case
      of thyrotoxicosis for initiation of antithyroid medication. His chief complaint
      was a swelling in front of the neck, which was incidentally noted by his mother 2
      weeks prior to presentation. He denied any history of symptoms suggestive of
      hyperthyroidism or ophthalmological involvement. His physical examination was
      unremarkable except for a grade 2 goitre. Thyroid function test revealed elevated
      free triiodothyronine and tetraiodothyronine in the face of an unsuppressed
      thyroid-stimulating hormone level. Technetium-99 uptake scan showed increased
      uptake indicating enhanced thyroid activity. However, he was clinically
      euthyroid. This raised the possibility of resistance to thyroid hormones, which
      was confirmed by documenting similar thyroid function test abnormalities in other
      members of his family and genetic testing. The family was reassured of the benign
      nature of the condition.

PMID- 29183898
TI  - Pirfenidone-induced hyponatraemia: insight in mechanism, risk factor and
      management.
AB  - Pirfenidone was approved in October 2014 in the USA for the treatment of
      idiopathic pulmonary fibrosis. Although not included in the adverse events
      published in the CAPACITY-1 and CAPACITY-2 or ASCEND trials, hyponatraemia was
      reported in supplementary data with rate of 3.4% in the active therapy arm versus
      0.3% in the placebo arm. We performed a retrospective analysis of patients who
      were initiated on pirfenidone or nintedanib for the treatment of pulmonary
      fibrosis at our centre. Of the 52 patients who were started on pirfenidone, three
      (5.8%) developed severe hyponatraemia. Of the 29 patients who were started on
      nintedanib, none developed hyponatraemia. Laboratory data suggested syndrome of
      inappropriate antidiuretic hormone secretion (SIADH) induced by pirfenidone and
      the medication was discontinued. Hyponatraemia is a possible significant adverse
      effect of pirfenidone, able to induce SIADH in patients taking the medication.

PMID- 29183900
TI  - Delayed presentation of iatrogenic bladder perforation.

PMID- 29183899
TI  - Fish hook injury: an easy removal using the string yank technique.

PMID- 29183901
TI  - Lesion in the external auditory canal: an unusual site for basal cell carcinoma.

PMID- 29183902
TI  - Puff laddy: a 5-year-old-boy with forehead swelling.

PMID- 29183903
TI  - Cancer-related microangiopathic haemolytic anaemia.

PMID- 29183904
TI  - Inverse hypopyon (hyperoleon) at the posterior segment in pathological myopia.

PMID- 29183905
TI  - Editorial board of public health journal quits after row with publisher.

PMID- 29183906
TI  - Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene
      expression programs essential for heart development and function.
AB  - How chromatin-remodeling complexes modulate gene networks to control organ
      specific properties is not well understood. For example, Baf60c (Smarcd3) encodes
      a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its
      role in heart development is not fully understood. We found that constitutive
      loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac
      dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in
      postnatal dilated cardiomyopathy with impaired contractile function. Baf60c
      regulates a gene expression program that includes genes encoding contractile
      proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of
      the genes deregulated in Baf60c null embryos are targets of the MEF2/SRF co
      factor Myocardin (MYOCD). In a yeast two-hybrid screen, we identified MYOCD as a
      BAF60c interacting factor; we showed that BAF60c and MYOCD directly and
      functionally interact. We conclude that Baf60c is essential for coordinating a
      program of gene expression that regulates the fundamental functional properties
      of cardiomyocytes.

PMID- 29183907
TI  - A dual transcript-discovery approach to improve the delimitation of gene features
      from RNA-seq data in the chicken model.
AB  - The sequence of the chicken genome, like several other draft genome sequences, is
      presently not fully covered. Gaps, contigs assigned with low confidence and
      uncharacterized chromosomes result in gene fragmentation and imprecise gene
      annotation. Transcript abundance estimation from RNA sequencing (RNA-seq) data
      relies on read quality, library complexity and expression normalization. In
      addition, the quality of the genome sequence used to map sequencing reads, and
      the gene annotation that defines gene features, must also be taken into account.
      A partially covered genome sequence causes the loss of sequencing reads from the
      mapping step, while an inaccurate definition of gene features induces imprecise
      read counts from the assignment step. Both steps can significantly bias
      interpretation of RNA-seq data. Here, we describe a dual transcript-discovery
      approach combining a genome-guided gene prediction and a de novo transcriptome
      assembly. This dual approach enabled us to increase the assignment rate of RNA
      seq data by nearly 20% as compared to when using only the chicken reference
      annotation, contributing therefore to a more accurate estimation of transcript
      abundance. More generally, this strategy could be applied to any organism with
      partial genome sequence and/or lacking a manually-curated reference annotation in
      order to improve the accuracy of gene expression studies.

PMID- 29183908
TI  - Modulation of GLP-1 Levels by a Genetic Variant That Regulates the Cardiovascular
      Effects of Intensive Glycemic Control in ACCORD.
AB  - OBJECTIVE: A genome-wide association study in the Action to Control
      Cardiovascular Risk in Diabetes (ACCORD) trial identified two markers (rs57922
      and rs9299870) that were significantly associated with cardiovascular mortality
      during intensive glycemic control and could potentially be used, when combined
      into a genetic risk score (GRS), to identify patients with diabetes likely to
      derive benefit from intensive control rather than harm. The aim of this study was
      to gain insights into the pathways involved in the modulatory effect of these
      variants. RESEARCH DESIGN AND METHODS: Fasting levels of 65 biomarkers were
      measured at baseline and at 12 months of follow-up in the ACCORD-Memory in
      Diabetes (ACCORD-MIND) MRI substudy (n = 562). Using linear regression models, we
      tested the association of the GRS with baseline and 12-month biomarker levels,
      and with their difference (Delta), among white subjects, with genotype data (n =
      351) stratified by intervention arm. RESULTS: A significant association was
      observed between GRS and DeltaGLP-1 (glucagon-like peptide 1, active) in the
      intensive arm (P = 3 * 10-4). This effect was driven by rs57922 (P = 5 * 10-4).
      C/C homozygotes, who had been found to derive cardiovascular benefits from
      intensive treatment, showed a 22% increase in GLP-1 levels during follow-up. By
      contrast, T/T homozygotes, who had been found to experience increased cardiac
      mortality with intensive treatment, showed a 28% reduction in GLP-1 levels. No
      association between DeltaGLP-1 and GRS or rs57922 was observed in the standard
      treatment arm. CONCLUSIONS: Differences in GLP-1 axis activation may mediate the
      modulatory effect of variant rs57922 on the cardiovascular response to intensive
      glycemic control. These findings highlight the importance of GLP-1 as a
      cardioprotective factor.

PMID- 29183909
TI  - Comparison of beta-Cell Function Between Overweight/Obese Adults and Adolescents
      Across the Spectrum of Glycemia.
AB  - OBJECTIVE: Type 2 diabetes is a growing health problem among both adults and
      adolescents. To better understand the differences in the pathogenesis of diabetes
      between these groups, we examined differences in beta-cell function along the
      spectrum of glucose tolerance. RESEARCH DESIGN AND METHODS: We evaluated 89
      adults and 50 adolescents with normal glucose tolerance (NGT), dysglycemia, or
      type 2 diabetes. Oral glucose tolerance test results were used for C-peptide and
      insulin/glucose minimal modeling. Model-derived and direct measures of insulin
      secretion and insulin sensitivity were compared across glycemic stages and
      between age-groups at each stage. RESULTS: In adolescents with dysglycemia, there
      was marked insulin resistance (insulin sensitivity index: adolescents, median
      [interquartile range] 1.8 [1.1-2.4] * 10-4; adults, 5.0 [2.3-9.9]; P = 0.01). The
      nature of beta-cell dysfunction across stages of dysglycemia differed between the
      groups. We observed higher levels of secretion among adolescents than adults
      (total insulin secretion: NGT, 143 [103-284] * 10-9/min adolescent vs. 106 [71
      127], P = 0.001); adults showed stepwise impairments in static insulin secretion
      (NGT, 7.5 [4.0-10.3] * 10-9/min; dysglycemia, 5.0 [2.3-9.9]; type 2 diabetes, 0.7
      [0.1-2.45]; P = 0.003), whereas adolescents showed diabetes-related impairment in
      dynamic secretion (NGT, 1,905 [1,630-3,913] * 10-9; dysglycemia, 2,703 [1,323
      3,637]; type 2 diabetes, 1,189 [269-1,410]; P = 0.001). CONCLUSIONS: Adults and
      adolescents differ in the underlying defects leading to dysglycemia, and in the
      nature of beta-cell dysfunction across stages of dysglycemia. These results may
      suggest different approaches to diabetes prevention in youths versus adults.

PMID- 29183911
TI  - David Oliver: Telehealth and telecare need a different approach.

PMID- 29183910
TI  - Predictors of Quality of Life and Other Patient-Reported Outcomes in the PANORAMA
      Multinational Study of People With Type 2 Diabetes.
AB  - OBJECTIVE: PANORAMA, a nine-country cross-sectional type 2 diabetes study,
      investigated factors associated with quality of life (QoL), health status, and
      other patient-reported outcome measures (PROMs). RESEARCH DESIGN AND METHODS:
      Patients were randomly or consecutively selected from primary/secondary care.
      PROMs included the Audit of Diabetes-Dependent Quality of Life (ADDQoL) (generic
      QoL item and average weighted impact [AWI] scores), Diabetes Treatment
      Satisfaction Questionnaire (DTSQ) (patient- and physician-completed),
      Hypoglycemia Fear Survey-II worry subscale, and the EuroQoL-5 Dimension visual
      analog scale (EQ-VAS) measuring patient-reported health. Multivariable linear
      regression analyses determined predictors of each PROM including patient
      characteristics, physician-reported adherence, complications, and glycosylated
      hemoglobin. RESULTS: In 5,813 patients, mean PROM scores indicated that generic
      QoL approximated "good" (0.93); perceived impact of diabetes on QoL was negative
      (AWI -1.69). Treatment satisfaction exceeded physicians' estimates (patient
      reported: 29.76; physician-estimated: 27.75), but so did patients' perceived
      frequency of hypo-/hyperglycemia. Worry about hypoglycemia (13.27) was apparent.
      Intensifying treatments to three oral agents or insulin regimens predicted worse
      QoL (AWI P < 0.01). Insulin alone use predicted worse QoL (generic P < 0.02; AWI
      P < 0.001) and hypoglycemia worry (P < 0.007). No treatment had significant
      associations with EQ-VAS health status. CONCLUSIONS: Predictors for different
      PROMs differed markedly and provided insights for understanding and improving
      these important outcomes. Intensive treatment regimens had significant negative
      associations with all PROMs, except the EQ-VAS health status measure. The
      findings demonstrate the importance of measuring QoL alongside health status and
      other patient-reported outcomes when evaluating diabetes treatments with a view
      to protecting QoL and facilitating adherence and long-term glycemic control.

PMID- 29183912
TI  - Japan's government warns against abnormal behaviour in people taking antivirals
      for flu.

PMID- 29183914
TI  - O-Glycome Beam Search Arrays for Carbohydrate Ligand Discovery.
AB  - O-glycosylation is a post-translational modification of proteins crucial to
      molecular mechanisms in health and disease. O-glycans are typically highly
      heterogeneous. The involvement of specific O-glycan sequences in many bio
      recognition systems is yet to be determined because of a lack of efficient
      methodologies. We describe here a targeted microarray approach: O-glycome beam
      search that is both robust and efficient for O-glycan ligand-discovery.
      Substantial simplification of the complex O-glycome profile and facile
      chromatographic resolution is achieved by arraying O-glycans as branches,
      monitoring by mass spectrometry, focusing on promising fractions, and on-array
      immuno-sequencing. This is orders of magnitude more sensitive than traditional
      methods. We have applied beam search approach to porcine stomach mucin and
      identified extremely minor components previously undetected within the O-glycome
      of this mucin that are ligands for the adhesive proteins of two rotaviruses. The
      approach is applicable to O-glycome recognition studies in a wide range of
      biological settings to give insights into glycan recognition structures in
      natural microenvironments.

PMID- 29183915
TI  - Yeast Hog1 proteins are sequestered in stress granules during high-temperature
      stress.
AB  - The yeast high-osmolarity glycerol (HOG) pathway plays a central role in stress
      responses. It is activated by various stresses, including hyperosmotic stress,
      oxidative stress, high-temperature stress and exposure to arsenite. Hog1, the
      crucial MAP kinase of the pathway, localizes to the nucleus in response to high
      osmotic concentrations, i.e. high osmolarity; but, otherwise, little is known
      about its intracellular dynamics and regulation. By using the methylotrophic
      yeast Candida boidinii, we found that CbHog1-Venus formed intracellular dot
      structures after high-temperature stress in a reversible manner. Microscopic
      observation revealed that CbHog1-mCherry colocalized with CbPab1-Venus, a marker
      protein of stress granules. Hog1 homologs in Pichia pastoris and
      Schizosaccharomyces pombe also exhibited similar dot formation under high
      temperature stress, whereas Saccharomyces cerevisiae Hog1 (ScHog1)-GFP did not.
      Analysis of CbHog1-Venus in C. boidinii revealed that a beta-sheet structure in
      the N-terminal region was necessary and sufficient for its localization to stress
      granules. Physiological studies revealed that sequestration of activated Hog1
      proteins in stress granules was responsible for downregulation of Hog1 activity
      under high-temperature stress.This article has an associated First Person
      interview with the first author of the paper.

PMID- 29183913
TI  - Spectral Library Based Analysis of Arginine Phosphorylations in Staphylococcus
      aureus.
AB  - Reversible protein phosphorylation is one of the major mechanisms in the
      regulation of protein expression and protein activity, controlling physiological
      functions of the important human pathogen Staphylococcus aureus Phosphorylations
      at serine, threonine and tyrosine are known to influence for example protein
      activity in central metabolic pathways and the more energy-rich phosphorylations
      at histidine, aspartate or cysteine can be found as part of two component system
      sensor domains or mediating bacterial virulence. In addition to these well-known
      phosphorylations, the phosphorylation at arginine residues plays an essential
      role. Hence, the deletion mutant S. aureus COL DeltaptpB (protein tyrosine
      phosphatase B) was studied because the protein PtpB is assumed to be an arginine
      phosphatase. A gel-free approach was applied to analyze the changes in the
      phosphoproteome of the deletion mutant DeltaptpB and the wild type in growing
      cells, thereby focusing on the occurrence of phosphorylation on arginine
      residues. In order to enhance the reliability of identified phosphorylation sites
      at arginine residues, a subset of arginine phosphorylated peptides was chemically
      synthesized. Combined spectral libraries based on phosphoenriched samples,
      synthetic arginine phosphorylated peptides and classical proteome samples provide
      a sophisticated tool for the analysis of arginine phosphorylations. This way, 212
      proteins phosphorylated on serine, threonine, tyrosine or arginine residues were
      identified within the mutant DeltaptpB and 102 in wild type samples. Among them,
      207 arginine phosphosites were identified exclusively within the mutant
      DeltaptpB, widely distributed along the whole bacterial metabolism. This
      identification of putative targets of PtpB allows further investigation of the
      physiological relevance of arginine phosphorylations and provides the basis for
      reliable quantification of arginine phosphorylations in bacteria.

PMID- 29183917
TI  - Implementation science at the crossroads.

PMID- 29183916
TI  - Ceruloplasmin replacement therapy ameliorates neurological symptoms in a
      preclinical model of aceruloplasminemia.
AB  - Aceruloplasminemia is a monogenic disease caused by mutations in the
      ceruloplasmin gene that result in loss of protein ferroxidase activity.
      Ceruloplasmin plays a role in iron homeostasis, and its activity impairment leads
      to iron accumulation in liver, pancreas, and brain. Iron deposition promotes
      diabetes, retinal degeneration, and progressive neurodegeneration. Current
      therapies mainly based on iron chelation, partially control systemic iron
      deposition but are ineffective on neurodegeneration. We investigated the
      potential of ceruloplasmin replacement therapy in reducing the neurological
      pathology in the ceruloplasmin-knockout (CpKO) mouse model of aceruloplasminemia.
      CpKO mice were intraperitoneal administered for 2 months with human ceruloplasmin
      that was able to enter the brain inducing replacement of the protein levels and
      rescue of ferroxidase activity. Ceruloplasmin-treated mice showed amelioration of
      motor incoordination that was associated with diminished loss of Purkinje neurons
      and reduced brain iron deposition, in particular in the choroid plexus.
      Computational analysis showed that ceruloplasmin-treated CpKO mice share a
      similar pattern with wild-type animals, highlighting the efficacy of the therapy.
      These data suggest that enzyme replacement therapy may be a promising strategy
      for the treatment of aceruloplasminemia.

PMID- 29183918
TI  - Factors Associated With Documentation of Obesity in the Inpatient Setting.
AB  - OBJECTIVES: Childhood obesity is rarely identified in hospitalized pediatric
      patients despite the high prevalence of obesity and potential for associated
      morbidity. The purpose of this study was to identify specific patient
      characteristics associated with the documentation of obesity and related weight
      management recommendations in the inpatient setting. METHODS: Retrospective chart
      review was conducted on all pediatric patients ages 2 to 18 years old and
      discharged between January 1, 2012, and December 31, 2014, to determine the
      following: (1) if obesity was noted in the clinical documentation of those with a
      BMI >=95th percentile; and (2) if those with documented obesity had evidence of
      an obesity-specific management plan. Using chi2 and multivariable logistic
      regression, we determined patient characteristics associated with the
      documentation of obesity and presence of a management plan. RESULTS: Only 26%
      (214 of 809) of inpatients with obesity had documentation of weight status. The
      odds of obesity documentation were higher in patients with comorbid
      cholelithiasis, severe obesity, and older age. Of those with obesity
      documentation, 23% (49 of 214) had an obesity management plan. Comorbid sleep
      apnea and admission to a surgical service with a pediatric hospital medicine
      consult were significantly associated with the presence of an obesity management
      plan. CONCLUSIONS: Increased efforts are necessary to improve obesity diagnosis
      and management in younger children who have not yet developed comorbidities.
      Additionally, the role of pediatric hospitalists as consultants for surgical
      patients should be further explored as a tool for addressing obesity during
      inpatient hospitalization.

PMID- 29183919
TI  - Managing alcohol-related attendances in emergency care: can diversion to bespoke
      services lessen the burden?
AB  - Acute alcohol intoxication (AAI) has a long history of burdening emergency care
      services. Healthcare systems around the world have explored a variety of
      different services that divert AAI away from EDs to better manage their
      condition. Little formal evaluation has been undertaken, particularly in the UK
      where alcohol misuse is one of the highest in the world. In this article, we
      outline a brief history of diversionary services, introduce the concept of
      Alcohol Intoxication Management Services (AIMS) and describe examples of AIMS in
      the UK. We then describe Evaluating the Diversion of Alcohol-Related Attendances,
      a natural experiment including six cities with AIMS compared with six cities
      without, that involves an ethnographic study, records patient experiences in both
      AIMS and EDs, assesses impact on key performance indicators in healthcare and
      evaluates the cost-effectiveness of AIMS.

PMID- 29183920
TI  - Reassessing the importance of 'lost pleasure' associated with smoking cessation:
      implications for social welfare and policy.
AB  - INTRODUCTION: Benefit-cost analyses of tobacco regulations include estimates of
      the informed choice of smokers to continue smoking. Few studies have focused on
      subjective feelings associated with continued smoking. This study estimates how
      smoker discontent and regret relate to risk perceptions and health concerns.
      METHODS: We analysed data from a 2015 nationally representative, online survey of
      1284 US adult current smokers. Information was collected on regret, intention to
      quit, perceived addiction, risk perceptions and health concerns. Multivariate
      logistic regression adjusting for sociodemographics and health status was used to
      examine factors associated with smoker discontent. RESULTS: More than 80% of
      current smokers report high (22.5%) or very high (59.8%) discontent due to
      inability to quit, perceived addiction and regret about having started to smoke.
      Higher levels of discontent did not vary significantly by sex, age,
      race/ethnicity, education or income (adjusted odds ratios (AORs) 0.5-1.2).
      Compared with the smokers expressing low (5.9%) or very low (3.6%) discontent,
      those expressing higher levels of discontent perceived their health status as
      fair/poor (AOR=2.3), worried most of the time about lung cancer (AOR=4.6) and
      felt they were more likely to develop lung cancer in the future (AOR=5.1).
      CONCLUSION: The proportion of smokers who might be characterised as having a
      preference to continue smoking are greatly outnumbered by addicted, discontent
      and concerned smokers who want to quit and regret ever having started to smoke.
      These discontent smokers could have a substantial net welfare gain if new
      regulations helped them escape their concerns about the health effects from
      continuing smoking.

PMID- 29183921
TI  - Diagnostic immunohistochemistry in gynaecological neoplasia: a brief survey of
      the most common scenarios.
AB  - Immunohistochemistry is a valuable adjunct in routine gynaecological pathology.
      The molecular revolution has redesigned knowledge of gynaecological cancers and
      refined histological classification. The direct consequence has been the
      progressive introduction of new immunostainings for diagnostic and classification
      purposes. Hence, we review the routine diagnostic use of immunohistochemistry in
      the field of gynaecological neoplasia. We reviewed the immunomarkers useful in
      gynaecological pathology according to literature revision, our personal
      experience and research findings. We discuss the application of
      immunohistochemistry to reach the most accurate diagnosis in morphologically
      equivocal cases of gynaecological pathology and present the appropriate panel of
      immunomarkers in the most common scenarios of gynaecological pathology. This
      short review provides an updated overview of the essential immunohistochemical
      markers currently used in the diagnostics of gynaecological malignancies along
      with their molecular rationale.

PMID- 29183922
TI  - Proton pump inhibitors and the risk for gastric cancer: possible confounding by
      serum vitamin B 12.

PMID- 29183923
TI  - RNA2DMut: a web tool for the design and analysis of RNA structure mutations.
AB  - With the widespread application of high-throughput sequencing, novel RNA
      sequences are being discovered at an astonishing rate. The analysis of function,
      however, lags behind. In both the cis- and trans-regulatory functions of RNA,
      secondary structure (2D base-pairing) plays essential regulatory roles. In order
      to test RNA function, it is essential to be able to design and analyze mutations
      that can affect structure. This was the motivation for the creation of the
      RNA2DMut web tool. With RNA2DMut, users can enter in RNA sequences to analyze,
      constrain mutations to specific residues, or limit changes to
      purines/pyrimidines. The sequence is analyzed at each base to determine the
      effect of every possible point mutation on 2D structure. The metrics used in
      RNA2DMut rely on the calculation of the Boltzmann structure ensemble and do not
      require a robust 2D model of RNA structure for designing mutations. This tool can
      facilitate a wide array of uses involving RNA: for example, in designing and
      evaluating mutants for biological assays, interrogating RNA-protein interactions,
      identifying key regions to alter in SELEX experiments, and improving RNA folding
      and crystallization properties for structural biology. Additional tools are
      available to help users introduce other mutations (e.g., indels and
      substitutions) and evaluate their effects on RNA structure. Example calculations
      are shown for five RNAs that require 2D structure for their function: the MALAT1
      mascRNA, an influenza virus splicing regulatory motif, the EBER2 viral noncoding
      RNA, the Xist lncRNA repA region, and human Y RNA 5. RNA2DMut can be accessed at
      https://rna2dmut.bb.iastate.edu/.

PMID- 29183924
TI  - Is there sufficient evidence regarding signage-based stair use interventions? A
      sequential meta-analysis.
AB  - OBJECTIVE: The proliferation of studies using motivational signs to promote stair
      use continues unabated, with their oft-cited potential for increasing population
      level physical activity participation. This study examined all stair use
      promotional signage studies since 1980, calculating pre-estimates and post
      estimates of stair use. The aim of this project was to conduct a sequential meta
      analysis to pool intervention effects, in order to determine when the evidence
      base was sufficient for population-wide dissemination. DESIGN: Using comparable
      data from 50 stair-promoting studies (57 unique estimates) we pooled data to
      assess the effect sizes of such interventions. RESULTS: At baseline, median stair
      usage across interventions was 8.1%, with an absolute median increase of 2.2% in
      stair use following signage-based interventions. The overall pooled OR indicated
      that participants were 52% more likely to use stairs after exposure to
      promotional signs (adjusted OR 1.52, 95% CI 1.37 to 1.70). Incremental
      (sequential) meta-analyses using z-score methods identified that sufficient
      evidence for stair use interventions has existed since 2006, with recent studies
      providing no further evidence on the effect sizes of such interventions.
      CONCLUSIONS: This analysis has important policy and practice implications.
      Researchers continue to publish stair use interventions without connection to
      policymakers' needs, and few stair use interventions are implemented at a
      population level. Researchers should move away from repeating short-term, small
      scale, stair sign interventions, to investigating their scalability, adoption and
      fidelity. Only such research translation efforts will provide sufficient evidence
      of external validity to inform their scaling up to influence population physical
      activity.

PMID- 29183925
TI  - Cohort profile: the TrueNTH Global Registry - an international registry to
      monitor and improve localised prostate cancer health outcomes.
AB  - PURPOSE: Globally, prostate cancer treatment and outcomes for men vary according
      to where they live, their race and the care they receive. The TrueNTH Global
      Registry project was established as an international registry monitoring care
      provided to men with localised prostate cancer (CaP). PARTICIPANTS: Sites with
      existing CaP databases in Movember fundraising countries were invited to
      participate in the international registry. In total, 25 Local Data Centres (LDCs)
      representing 113 participating sites across 13 countries have nominated to
      contribute to the project. It will collect a dataset based on the International
      Consortium for Health Outcome Measures (ICHOM) standardised dataset for localised
      CaP. FINDINGS TO DATE: A governance strategy has been developed to oversee
      registry operation, including transmission of reversibly anonymised data. LDCs
      are represented on the Project Steering Committee, reporting to an Executive
      Committee. A Project Coordination Centre and Data Coordination Centre (DCC) have
      been established. A project was undertaken to compare existing datasets,
      understand capacity at project commencement (baseline) to collect the ICHOM
      dataset and assist in determining the final data dictionary. 21/25 LDCs provided
      data dictionaries for review. Some ICHOM data fields were well collected
      (diagnosis, treatment start dates) and others poorly collected (complications,
      comorbidities). 17/94 (18%) ICHOM data fields were relegated to non-mandatory
      fields due to poor capture by most existing registries. Participating sites will
      transmit data through a web interface biannually to the DCC. FUTURE PLANS:
      Recruitment to the TrueNTH Global Registry-PCOR project will commence in late
      2017 with sites progressively contributing reversibly anonymised data following
      ethical review in local regions. Researchers will have capacity to source
      deidentified data after the establishment phase. Quality indicators are to be
      established through a modified Delphi approach in later 2017, and it is
      anticipated that reports on performance against quality indicators will be
      provided to LDCs.

PMID- 29183926
TI  - Protocol for a feasibility randomised controlled trial of Screening and Enhanced
      Risk management for Vascular Event-related Decline in Memory (SERVED Memory).
AB  - INTRODUCTION: Stroke is a leading cause of death and disability. The development
      of dementia after stroke is common. Vascular risk factors (VRF) which contribute
      to stroke risk can also contribute to cognitive decline, especially in vascular
      dementia (VaD). There is no established treatment for VaD, therefore strategies
      for prevention could have major health resource implications. This study was
      designed to assess whether patients with early cognitive decline after
      stroke/transient ischaemic attack (TIA) can be easily identified and whether
      target-driven VRF management can prevent progression to dementia. OBJECTIVES: The
      primary objective is to establish the feasibility of recruitment and retention of
      patients with early cognitive decline to a randomised controlled trial of
      enhanced VRF management. Secondary objectives include: (a) to determine the
      potential clinical benefit of the intervention; (b) to estimate the sample size
      for a future definitive multicentre randomised controlled trial; (c) to inform a
      future economic evaluation; (d) to explore the link between VRF control and the
      incidence of cognitive impairment on longitudinal follow-up in a UK population
      after stroke/TIA with current routine management. METHODS: 100 patients with
      cognitive decline poststroke/TIA will be recruited from stroke services at the
      Norfolk and Norwich University Hospital. After collection of baseline data, they
      will be randomised to intervention (3 monthly follow-up with enhanced management)
      or control (treatment as usual by the general practitioner). At 12 months
      outcomes (repeat cognitive testing, VRF assessment) will be assessed. A further
      100 patients without cognitive decline will be recruited to a parallel
      observational group from the same site. At 12 months they will have repeat
      cognitive testing. ETHICS AND DISSEMINATION: Ethical approval has been granted in
      England. Dissemination is planned via publication in peer-reviewed medical
      journals and presentation at relevant conferences. TRIAL REGISTRATION NUMBER:
      42688361; Pre-results.

PMID- 29183927
TI  - Challenges to discussing palliative care with people experiencing homelessness: a
      qualitative study.
AB  - OBJECTIVES: To explore the views and experiences of people who are homeless and
      those supporting them regarding conversations and approaches to palliative care
      SETTING: Data were collected between October 2015 and October 2016 in homeless
      hostels and day centres and with staff from primary and secondary healthcare
      providers and social care services from three London boroughs. PARTICIPANTS:
      People experiencing homelessness (n=28), formerly homeless people (n=10), health
      and social care providers (n=48), hostel staff (n=30) and outreach staff (n=10).
      METHODS: In this qualitative descriptive study, participants were recruited to
      interviews and focus groups across three London boroughs. Views and experiences
      of end-of-life care were explored with people with personal experience of
      homelessness, health and social care professionals and hostel and outreach staff.
      Saturation was reached when no new themes emerged from discussions. RESULTS: 28
      focus groups and 10 individual interviews were conducted. Participants
      highlighted that conversations exploring future care preferences and palliative
      care with people experiencing homelessness are rare. Themes identified as
      challenges to such conversations included attitudes to death; the recovery
      focused nature of services for people experiencing homelessness; uncertainty
      regarding prognosis and place of care; and fear of negative impact. CONCLUSIONS:
      This research highlights the need for a different approach to supporting people
      who are homeless and are experiencing advanced ill health, one that incorporates
      uncertainty and promotes well-being, dignity and choice. We propose parallel
      planning and mapping as a way of working with uncertainty. We acknowledge that
      these approaches will not always be straightforward, nor will they be suitable
      for everyone, yet moving the focus of conversations about the future away from
      death and dying, towards the present and the future may facilitate conversations
      and enable the wishes of people who are homeless to be known and explored.

PMID- 29183928
TI  - Viability testing and transplantation of marginal livers (VITTAL) using
      normothermic machine perfusion: study protocol for an open-label, non-randomised,
      prospective, single-arm trial.
AB  - INTRODUCTION: The use of marginal or extended criteria donor livers is
      increasing. These organs carry a greater risk of initial dysfunction and early
      failure, as well as inferior long-term outcomes. As such, many are rejected due
      to a perceived risk of use and use varies widely between centres. Ex situ
      normothermic machine perfusion of the liver (NMP-L) may enable the safe
      transplantation of organs that meet defined objective criteria denoting their
      high-risk status and are currently being declined for use by all the UK
      transplant centres. METHODS AND ANALYSIS: Viability testing and transplantation
      of marginal livers is an open-label, non-randomised, prospective, single-arm
      trial designed to determine whether currently unused donor livers can be salvaged
      and safely transplanted with equivalent outcomes in terms of patient survival.
      The procured rejected livers must meet predefined criteria that objectively
      denote their marginal condition. The liver is subjected to NMP-L following a
      period of static cold storage. Organs metabolising lactate to <=2.5 mmol/L within
      4 hours of the perfusion commencing in combination with two or more of the
      following parameters-bile production, metabolism of glucose, a hepatic arterial
      flow rate >=150 mL/min and a portal venous flow rate >=500 mL/min, a pH >=7.30
      and/or maintain a homogeneous perfusion-will be considered viable and
      transplanted into a suitable consented recipient. The coprimary outcome measures
      are the success rate of NMP-L to produce a transplantable organ and 90-day
      patient post-transplant survival. ETHICS AND DISSEMINATION: The protocol was
      approved by the National Research Ethics Service (London-Dulwich Research Ethics
      Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency
      and is endorsed by the National Health Service Blood and Transplant Research,
      Innovation and Novel Technologies Advisory Group. The findings of this trial will
      be disseminated through national and international presentations and peer
      reviewed publications. TRIAL REGISTRATION NUMBER: NCT02740608; Pre-results.

PMID- 29183929
TI  - Effectiveness of inhaled corticosteroids in real life on clinical outcomes,
      sputum cells and systemic inflammation in asthmatics: a retrospective cohort
      study in a secondary care centre.
AB  - OBJECTIVES: The impact of inhaled corticosteroids (ICS) on eosinophilic
      inflammation in asthma is well established, but their effect in a real-life
      setting has not been extensively studied. Our purpose was to investigate the
      effect of ICS on airway and systemic inflammation as well as on clinical outcomes
      in patients with asthma from clinical practice. DESIGN, SETTING AND PARTICIPANTS:
      We conducted a retrospective analysis on asthmatics from a secondary care centre
      in whom ICS were initiated/increased (n=101), stopped/decreased (n=60) or
      remained stable (n=63, used as a control group) between two visits with available
      sputum and blood cell counts. RESULTS: The median time between both visits ranged
      from 1 to 2 years. Initiating or increasing ICS (median variation (IQR): 800 (400
      1200) ug beclomethasone equivalent dose per day) reduced sputum eosinophils and
      fractional exhaled nitric oxide (P<0.0001) and to a lesser extent blood
      eosinophils (P<0.0001), while withdrawing or decreasing ICS (median variation
      (IQR): 900 (500-1200) ug beclomethasone equivalentdose per day) resulted in
      increased sputum eosinophils (P=0.008). No change was found in patients with a
      stable dose. The effectiveness of ICS in improving asthma control, quality of
      life, forced expiratory volume in 1 s (FEV1), bronchial hyper-responsiveness and
      exacerbation rate was only observed in the eosinophilic phenotype (sputum
      eosinophils >=3%, n=79). In non-eosinophilic asthmatics, stepping-down ICS
      resulted in an improvement in asthma control and quality of life, without any
      significant change in FEV1 (n=38). CONCLUSIONS: Our results confirm the
      effectiveness of ICS on eosinophilic inflammation in real life and demonstrate
      that their clinical benefit seems to be restricted to eosinophilic asthmatics.
      Our data also support a try for stepping-down ICS in non-eosinophilic asthmatics.

PMID- 29183930
TI  - Reducing catheter-associated urinary tract infections in hospitals: study
      protocol for a multi-site randomised controlled study.
AB  - INTRODUCTION: Despite advances in infection prevention and control, catheter
      associated urinary tract infections (CAUTIs) are common and remain problematic. A
      number of measures can be taken to reduce the risk of CAUTI in hospitals.
      Appropriate urinary catheter insertion procedures are one such method. Reducing
      bacterial colonisation around the meatal or urethral area has the potential to
      reduce CAUTI risk. However, evidence about the best antiseptic solutions for
      meatal cleaning is mixed, resulting in conflicting recommendations in guidelines
      internationally. This paper presents the protocol for a study to evaluate the
      effectiveness (objective 1) and cost-effectiveness (objective 2) of using
      chlorhexidine in meatal cleaning prior to catheter insertion, in reducing
      catheter-associated asymptomatic bacteriuria and CAUTI. METHODS AND ANALYSIS: A
      stepped wedge randomised controlled trial will be undertaken in three large
      Australian hospitals over a 32-week period. The intervention in this study is the
      use of chlorhexidine (0.1%) solution for meatal cleaning prior to catheter
      insertion. During the first 8 weeks of the study, no hospital will receive the
      intervention. After 8 weeks, one hospital will cross over to the intervention
      with the other two participating hospitals crossing over to the intervention at 8
      week intervals respectively based on randomisation. All sites complete the trial
      at the same time in 2018. The primary outcomes for objective 1 (effectiveness)
      are the number of cases of CAUTI and catheter-associated asymptomatic bacteriuria
      per 100 catheter days will be analysed separately using Poisson regression. The
      primary outcome for objective 2 (cost-effectiveness) is the changes in costs
      relative to health benefits (incremental cost-effectiveness ratio) from adoption
      of the intervention. DISSEMINATION: Results will be disseminated via peer
      reviewed journals and presentations at relevant conferences.A dissemination plan
      it being developed. Results will be published in the peer review literature,
      presented at relevant conferences and communicated via professional networks.
      ETHICS: Ethics approval has been obtained. TRIAL REGISTRATION NUMBER:
      12617000373370, approved 13/03/2017. Protocol version 1.1.

PMID- 29183931
TI  - Early low-energy versus high-energy enteral nutrition support in patients with
      traumatic intracerebral haemorrhage: protocol for a randomised controlled trial.
AB  - BACKGROUND: Early enteral nutrition (EN) is associated with shorter hospital stay
      and lower infection and mortality rates in patients with intracerebral
      haemorrhage. However, high-energy support always causes clinical complications,
      such as diarrhoea and aspiration pneumonia, and the true benefit of high-energy
      support in these patients has not been investigated. The appropriate amount of
      energy support still needs further investigation. Therefore, we are performing a
      randomised controlled trial to investigate whether early low-energy EN can
      decrease mortality and feeding-related complications and improve neurological
      outcomes as compared with high-energy EN in traumatic intracerebral haemorrhage
      (TICH) patients. METHODS/ANALYSIS: This is a randomised, single-blind clinical
      trial performed in one teaching hospital. 220 TICH patients will be randomly
      allocated to one of two groups in a 1:1 ratio: an intervention group, and a
      control group. The intervention group will receive early low-energy EN (10
      kcal/kg/day) and the control group will receive high-energy EN (25 kcal/kg/day)
      for 7 days. All these patients will be followed up for 90 days. The primary
      outcome is all-cause 90-day mortality. Secondary outcomes include the modified
      Rankin score, Glasgow Outcome Scale (GOS) and the National Institutes of Health
      Stroke Scale (NIHSS). Outcomes will be assessed at admission, 7, 30 and 90 days
      after onset of this trial. The safety of EN strategies will be assessed every day
      during hospitalisation. ETHICS AND DISSEMINATION: The trial will be conducted in
      accordance with the Declaration of Helsinki and has been approved by the ethics
      committee of Dongyang People's Hospital. The findings will be published in peer
      reviewed medical journals. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17011384; Pre
      results.

PMID- 29183932
TI  - Morphogenesis one century after On Growth and Form.

PMID- 29183933
TI  - On Growth and Form in context - an interview with Matthew Jarron.
AB  - D'Arcy Thompson was born in 1860, trained in Edinburgh and Cambridge, and held
      positions in Dundee and St Andrews, where he worked until his death in 1948. On
      Growth and Form, his classic work on the mathematical patterns and physical rules
      underlying biological forms, was first published in 1917. To learn more about the
      book's context, we met Matthew Jarron, Curator of Museum Services at the
      University of Dundee, in the University's D'Arcy Thompson Zoology Museum.
      Surrounded by specimens, many of which were collected by Thompson himself, we
      discussed the legacy of On Growth and Form and the life of the man behind it.

PMID- 29183934
TI  - On genes and form.
AB  - The mechanisms by which organisms acquire their sizes and shapes through growth
      was a major focus of D'Arcy Thompson's book On Growth and Form. By applying
      mathematical and physical principles to a range of biological forms, Thompson
      achieved fresh insights, such as the notion that diverse biological shapes could
      be related through simple deformations of a coordinate system. However, Thompson
      considered genetics to lie outside the scope of his work, even though genetics
      was a growing discipline at the time the book was published. Here, we review how
      recent advances in cell, developmental, evolutionary and computational biology
      allow Thompson's ideas to be integrated with genes and the processes they
      influence to provide a deeper understanding of growth and morphogenesis. We
      consider how genes interact with subcellular-, cellular- and tissue-level
      processes in plants to yield patterns of growth that underlie the developmental
      and evolutionary shape transformations Thompson so eloquently described.

PMID- 29183935
TI  - Computer modeling in developmental biology: growing today, essential tomorrow.
AB  - D'Arcy Thompson was a true pioneer, applying mathematical concepts and analyses
      to the question of morphogenesis over 100 years ago. The centenary of his famous
      book, On Growth and Form, is therefore a great occasion on which to review the
      types of computer modeling now being pursued to understand the development of
      organs and organisms. Here, I present some of the latest modeling projects in the
      field, covering a wide range of developmental biology concepts, from molecular
      patterning to tissue morphogenesis. Rather than classifying them according to
      scientific question, or scale of problem, I focus instead on the different ways
      that modeling contributes to the scientific process and discuss the likely future
      of modeling in developmental biology.

PMID- 29183936
TI  - 'The Forms of Tissues, or Cell-aggregates': D'Arcy Thompson's influence and its
      limits.
AB  - In two chapters of his book On Growth and Form, D'Arcy Thompson used numerous
      biological and physical observations to show how principles from mathematics and
      physics - such as pressure differences, surface tension and viscosity - could
      explain cell shapes and packing within tissues. In this Review, we depict
      influences that enabled the genesis of his ideas, report examples of his
      visionary observations and trace his impact over the past 100 years. Recently,
      his ideas have been revisited as a new field of research emerged, linking cell
      level physics with epithelial tissue structure and development. We critically
      discuss the potential and the limitations of both Thompson's and the modern
      approaches.

PMID- 29183937
TI  - Mechanical control of growth: ideas, facts and challenges.
AB  - In his classic book On Growth and Form, D'Arcy Thompson discussed the necessity
      of a physical and mathematical approach to understanding the relationship between
      growth and form. The past century has seen extraordinary advances in our
      understanding of biological components and processes contributing to organismal
      morphogenesis, but the mathematical and physical principles involved have not
      received comparable attention. The most obvious entry of physics into
      morphogenesis is via tissue mechanics. In this Review, we discuss the fundamental
      role of mechanical interactions between cells induced by growth in shaping a
      tissue. Non-uniform growth can lead to accumulation of mechanical stress, which
      in the context of two-dimensional sheets of tissue can specify the shape it
      assumes in three dimensions. A special class of growth patterns - conformal
      growth - does not lead to the accumulation of stress and can generate a rich
      variety of planar tissue shapes. Conversely, mechanical stress can provide a
      regulatory feedback signal into the growth control circuit. Both theory and
      experiment support a key role for mechanical interactions in shaping tissues and,
      via mechanical feedback, controlling epithelial growth.

PMID- 29183938
TI  - Tension, contraction and tissue morphogenesis.
AB  - D'Arcy Thompson was a proponent of applying mathematical and physical principles
      to biological systems, an approach that is becoming increasingly common in
      developmental biology. Indeed, the recent integration of quantitative
      experimental data, force measurements and mathematical modeling has changed our
      understanding of morphogenesis - the shaping of an organism during development.
      Emerging evidence suggests that the subcellular organization of contractile
      cytoskeletal networks plays a key role in force generation, while on the tissue
      level the spatial organization of forces determines the morphogenetic output.
      Inspired by D'Arcy Thompson's On Growth and Form, we review our current
      understanding of how biological forms are created and maintained by the
      generation and organization of contractile forces at the cell and tissue levels.
      We focus on recent advances in our understanding of how cells actively sculpt
      tissues and how forces are involved in specific morphogenetic processes.

PMID- 29183940
TI  - Mechanical regulation of musculoskeletal system development.
AB  - During embryogenesis, the musculoskeletal system develops while containing within
      itself a force generator in the form of the musculature. This generator becomes
      functional relatively early in development, exerting an increasing mechanical
      load on neighboring tissues as development proceeds. A growing body of evidence
      indicates that such mechanical forces can be translated into signals that combine
      with the genetic program of organogenesis. This unique situation presents both a
      major challenge and an opportunity to the other tissues of the musculoskeletal
      system, namely bones, joints, tendons, ligaments and the tissues connecting them.
      Here, we summarize the involvement of muscle-induced mechanical forces in the
      development of various vertebrate musculoskeletal components and their
      integration into one functional unit.

PMID- 29183941
TI  - The old and new faces of morphology: the legacy of D'Arcy Thompson's 'theory of
      transformations' and 'laws of growth'.
AB  - In 1917, the publication of On Growth and Form by D'Arcy Wentworth Thompson
      challenged both mathematicians and naturalists to think about biological shapes
      and diversity as more than a confusion of chaotic forms generated at random, but
      rather as geometric shapes that could be described by principles of physics and
      mathematics. Thompson's work was based on the ideas of Galileo and Goethe on
      morphology and of Russell on functionalism, but he was first to postulate that
      physical forces and internal growth parameters regulate biological forms and
      could be revealed via geometric transformations in morphological space. Such
      precise mathematical structure suggested a unifying generative process, as
      reflected in the title of the book. To Thompson it was growth that could explain
      the generation of any particular biological form, and changes in ontogeny, rather
      than natural selection, could then explain the diversity of biological shapes.
      Whereas adaptationism, widely accepted in evolutionary biology, gives primacy to
      extrinsic factors in producing morphological variation, Thompson's 'laws of
      growth' provide intrinsic directives and constraints for the generation of
      individual shapes, helping to explain the 'profusion of forms, colours, and other
      modifications' observed in the living world.

PMID- 29183939
TI  - Understanding the extracellular forces that determine cell fate and maintenance.
AB  - Stem cells interpret signals from their microenvironment while simultaneously
      modifying the niche through secreting factors and exerting mechanical forces.
      Many soluble stem cell cues have been determined over the past century, but in
      the past decade, our molecular understanding of mechanobiology has advanced to
      explain how passive and active forces induce similar signaling cascades that
      drive self-renewal, migration, differentiation or a combination of these
      outcomes. Improvements in stem cell culture methods, materials and biophysical
      tools that assess function have improved our understanding of these cascades.
      Here, we summarize these advances and offer perspective on ongoing challenges.

PMID- 29183942
TI  - Single-cell mechanical phenotype is an intrinsic marker of reprogramming and
      differentiation along the mouse neural lineage.
AB  - Cellular reprogramming is a dedifferentiation process during which cells
      continuously undergo phenotypical remodeling. Although the genetic and
      biochemical details of this remodeling are fairly well understood, little is
      known about the change in cell mechanical properties during the process. In this
      study, we investigated changes in the mechanical phenotype of murine fetal neural
      progenitor cells (fNPCs) during reprogramming to induced pluripotent stem cells
      (iPSCs). We find that fNPCs become progressively stiffer en route to
      pluripotency, and that this stiffening is mirrored by iPSCs becoming more
      compliant during differentiation towards the neural lineage. Furthermore, we show
      that the mechanical phenotype of iPSCs is comparable with that of embryonic stem
      cells. These results suggest that mechanical properties of cells are inherent to
      their developmental stage. They also reveal that pluripotent cells can
      differentiate towards a more compliant phenotype, which challenges the view that
      pluripotent stem cells are less stiff than any cells more advanced
      developmentally. Finally, our study indicates that the cell mechanical phenotype
      might be utilized as an inherent biophysical marker of pluripotent stem cells.

PMID- 29183943
TI  - Anisotropic shear stress patterns predict the orientation of convergent tissue
      movements in the embryonic heart.
AB  - Myocardial contractility and blood flow provide essential mechanical cues for the
      morphogenesis of the heart. In general, endothelial cells change their migratory
      behavior in response to shear stress patterns, according to flow directionality.
      Here, we assessed the impact of shear stress patterns and flow directionality on
      the behavior of endocardial cells, the specialized endothelial cells of the
      heart. At the early stages of zebrafish heart valve formation, we show that
      endocardial cells are converging to the valve-forming area and that this behavior
      depends upon mechanical forces. Quantitative live imaging and mathematical
      modeling allow us to correlate this tissue convergence with the underlying flow
      forces. We predict that tissue convergence is associated with the direction of
      the mean wall shear stress and of the gradient of harmonic phase-averaged shear
      stresses, which surprisingly do not match the overall direction of the flow. This
      contrasts with the usual role of flow directionality in vascular development and
      suggests that the full spatial and temporal complexity of the wall shear stress
      should be taken into account when studying endothelial cell responses to flow in
      vivo.

PMID- 29183944
TI  - Clones of cells switch from reduction to enhancement of size variability in
      Arabidopsis sepals.
AB  - Organs form with remarkably consistent sizes and shapes during development,
      whereas a high variability in growth is observed at the cell level. Given this
      contrast, it is unclear how such consistency in organ scale can emerge from
      cellular behavior. Here, we examine an intermediate scale, the growth of clones
      of cells in Arabidopsis sepals. Each clone consists of the progeny of a single
      progenitor cell. At early stages, we find that clones derived from a small
      progenitor cell grow faster than those derived from a large progenitor cell. This
      results in a reduction in clone size variability, a phenomenon we refer to as
      size uniformization. By contrast, at later stages of clone growth, clones change
      their growth pattern to enhance size variability, when clones derived from larger
      progenitor cells grow faster than those derived from smaller progenitor cells.
      Finally, we find that, at early stages, fast growing clones exhibit greater cell
      growth heterogeneity. Thus, cellular variability in growth might contribute to a
      decrease in the variability of clones throughout the sepal.

PMID- 29183945
TI  - Organ size control via hydraulically gated oscillations.
AB  - Hollow vesicular tissues of various sizes and shapes arise in biological organs
      such as ears, guts, hearts, brains and even entire organisms. Regulating their
      size and shape is crucial for their function. Although chemical signaling has
      been thought to play a role in the regulation of cellular processes that feed
      into larger scales, it is increasingly recognized that mechanical forces are
      involved in the modulation of size and shape at larger length scales. Motivated
      by a variety of examples of tissue cyst formation and size control that show
      simultaneous growth and size oscillations, we create a minimal theoretical
      framework for the growth and dynamics of a soft, fluid-permeable, spherical
      shell. We show that these shells can relieve internal pressure by bursting
      intermittently, shrinking and re-growing, providing a simple mechanism by which
      hydraulically gated oscillations can regulate size. To test our theory, we
      develop an in vitro experimental set-up to monitor the growth and oscillations of
      a hollow tissue spheroid growing freely or when confined. A simple generalization
      of our theory to account for irreversible deformations allows us to explain the
      time scales and the amplitudes of oscillations in terms of the geometry and
      mechanical properties of the tissue shells. Taken together, our theory and
      experimental observations show how soft hydraulics can regulate the size of
      growing tissue shells.

PMID- 29183946
TI  - An asymmetric attraction model for the diversity and robustness of cell
      arrangement in nematodes.
AB  - During early embryogenesis in animals, cells are arranged into a species-specific
      pattern in a robust manner. Diverse cell arrangement patterns are observed, even
      among close relatives. In the present study, we evaluated the mechanisms by which
      the diversity and robustness of cell arrangements are achieved in developing
      embryos. We successfully reproduced various patterns of cell arrangements
      observed in various nematode species in Caenorhabditis elegans embryos by
      altering the eggshell shapes. The findings suggest that the observed diversity of
      cell arrangements can be explained by differences in the eggshell shape.
      Additionally, we found that the cell arrangement was robust against eggshell
      deformation. Computational modeling revealed that, in addition to repulsive
      forces, attractive forces are sufficient to achieve such robustness. The present
      model is also capable of simulating the effect of changing cell division
      orientation. Genetic perturbation experiments demonstrated that attractive forces
      derived from cell adhesion are necessary for the robustness. The proposed model
      accounts for both diversity and robustness of cell arrangements, and contributes
      to our understanding of how the diversity and robustness of cell arrangements are
      achieved in developing embryos.

PMID- 29183947
TI  - Total workload and recovery in relation to worktime reduction: a randomised
      controlled intervention study with time-use data.
AB  - OBJECTIVES: A 25% reduction of weekly work hours for full-time employees has been
      shown to improve sleep and alertness and reduce stress during both workdays and
      days off. The aim of the present study was to investigate how employees use their
      time during such an intervention: does total workload (paid and non-paid work)
      decrease, and recovery time increase, when work hours are reduced? METHODS: Full
      time employees within the public sector (n=636; 75% women) were randomised into
      intervention group and control group. The intervention group (n=370) reduced
      worktime to 75% with preserved salary during 18 months. Data were collected at
      baseline, after 9 months and 18 months. Time-use was reported every half-hour
      daily between 06:00 and 01:00 during 1 week at each data collection. Data were
      analysed with multilevel mixed modelling. RESULTS: Compared with the control
      group, the intervention group increased the time spent on domestic work and
      relaxing hobby activities during workdays when worktime was reduced (P<=0.001).
      On days off, more time was spent in free-time activities (P=0.003). Total
      workload decreased (-65 min) and time spent in recovery activities increased on
      workdays (+53 min). The pattern of findings was similar in subgroups defined by
      gender, family status and job situation. CONCLUSIONS: A worktime reduction of 25%
      for full-time workers resulted in decreased total workload and an increase of
      time spent in recovery activities, which is in line with the suggestion that
      worktime reduction may be beneficial for long-term health and stress.

PMID- 29183948
TI  - Letter by Zaman et al Regarding Article, "Safety Outcomes After Percutaneous
      Transcatheter Closure of Patent Foramen Ovale".

PMID- 29183949
TI  - Response by Merkler et al to Letter Regarding Article, "Safety Outcomes After
      Percutaneous Transcatheter Closure of Patent Foramen Ovale".

PMID- 29183950
TI  - Response by Fouda and Switzer to Letter Regarding Article, "Minocycline in Acute
      Cerebral Hemorrhage: An Early Phase Randomized Trial".

PMID- 29183951
TI  - Letter by Chang et al Regarding Article, "Minocycline in Acute Cerebral
      Hemorrhage: An Early Phase Randomized Trial".

PMID- 29183952
TI  - Cerebellar Hematoma Location: Implications for the Underlying Microangiopathy.
AB  - BACKGROUND AND PURPOSE: Spontaneous cerebellar intracerebral hemorrhage (ICH) has
      been reported to be mainly associated with vascular changes secondary to
      hypertension. However, a subgroup of cerebellar ICH seems related to vascular
      amyloid deposition (cerebral amyloid angiopathy). We sought to determine whether
      location of hematoma in the cerebellum (deep and superficial regions) was
      suggestive of a particular hemorrhage-prone small-vessel disease pathology
      (cerebral amyloid angiopathy or hypertensive vasculopathy). METHODS: Consecutive
      patients with cerebellar ICH from a single tertiary care medical center were
      recruited. Based on data from pathological reports, patients were divided
      according to the location of the primary cerebellar hematoma (deep versus
      superficial). Location of cerebral microbleeds (CMBs; strictly lobar, strictly
      deep, and mixed CMB) was evaluated on magnetic resonance imaging. RESULTS: One
      hundred and eight patients (84%) had a deep cerebellar hematoma, and 20 (16%) a
      superficial cerebellar hematoma. Hypertension was more prevalent in deep than in
      patients with superficial cerebellar ICH (89% versus 65%, respectively; P<0.05).
      Among patients who underwent magnetic resonance imaging, those with superficial
      cerebellar ICH had higher prevalence of strictly lobar CMB (43%) and lower
      prevalence of strictly deep or mixed CMB (0%) compared with those with deep
      superficial cerebellar ICH (6%, 17%, and 38%, respectively). In a multivariable
      model, presence of strictly lobar CMB was associated with superficial cerebellar
      ICH (odds ratio, 3.8; 95% confidence interval, 1.5-8.5; P=0.004). CONCLUSIONS:
      Our study showed that superficial cerebellar ICH is related to the presence of
      strictly lobar CMB-a pathologically proven marker of cerebral amyloid angiopathy.
      Cerebellar hematoma location may thus help to identify those patients likely to
      have cerebral amyloid angiopathy pathology.

PMID- 29183953
TI  - Determinants of Informal Care, Burden, and Risk of Burnout in Caregivers of
      Stroke Survivors: The CONOCES Study.
AB  - BACKGROUND AND PURPOSE: The aim of this article was to analyze the likelihood of
      receiving informal care after a stroke and to study the burden and risk of
      burnout of primary caregivers in Spain. METHODS: The CONOCES study is an
      epidemiological, observational, prospective, multicenter study of patients
      diagnosed with stroke and admitted to a Stroke Unit in the Spanish healthcare
      system. At 3 and 12 months post-event, we estimated the time spent caring for the
      patient and the burden borne by primary caregivers. Several multivariate models
      were applied to estimate the likelihood of receiving informal caregiving, the
      burden, and the likelihood of caregivers being at a high risk of burnout.
      RESULTS: Eighty percent of those still alive at 3 and 12 months poststroke were
      receiving informal care. More than 40% of those receiving care needed a secondary
      caregiver at 3 months poststroke. The likelihood of receiving informal care was
      associated with stroke severity and the individual's health-related quality of
      life. When informal care was provided, both the burden borne by caregivers and
      the likelihood of caregivers being at a high risk of burnout was associated with
      (1) caregiving hours; (2) the patient's health-related quality of life; (3) the
      severity of the stroke measured at discharge; (4) the patient having atrial
      fibrillation; and (5) the degree of dependence. CONCLUSIONS: This study reveals
      the heavy burden borne by the caregivers of stroke survivors. Our analysis also
      identifies explanatory and predictive variables for the likelihood of receiving
      informal care, caregiver burden, and high risk of burnout.

PMID- 29183954
TI  - Associations between objectively measured physical activity and later mental
      health outcomes in children: findings from the UK Millennium Cohort Study.
AB  - BACKGROUND: The beneficial effect of physical activity (PA) on mental health in
      adults is well established, but less is known about this relationship in
      children. We examine associations between objectively measured sedentary time, PA
      and mental health in 11-year-olds from the UK Millennium Cohort Study (MCS).
      METHODS: Longitudinal data from MCS sweeps 4 (age 7) and 5 (age 11) were used
      (n=6153). Accelerometer data were collected at MCS4, and mental health was
      measured at MCS4 and MCS5 using subscales (peer, emotional, conduct,
      hyperactivity) of the Strengths and Difficulties Questionnaire (SDQ).
      Associations between mean daily PA minutes at different intensities (sedentary,
      light, moderate-to-vigorous) at MCS4 and SDQ outcomes at MCS5 (score range 0-10)
      were estimated using multiple linear regression models, adjusting for SDQ at MCS4
      and individual and family characteristics, and stratified by gender. RESULTS: In
      fully adjusted models, increased PA at MCS4 was associated with fewer peer
      problems in boys and girls at MCS5. For each additional 15 min in moderate-to
      vigorous physical activity (MVPA), peer problems decreased -0.077 points (95% CI 
      0.133 to -0.022) in boys. For girls, light PA was associated with decreased peer
      problems (-0.071 points/30 min, 95% CI -0.130 to -0.013). Greater sedentary time
      was associated with more peer problems and fewer hyperactivity symptoms in boys
      and girls. Increased MVPA was associated with more conduct and hyperactivity
      problems in boys and more hyperactivity in girls. CONCLUSIONS: Increased
      sedentary time is associated with more peer problems in children, and PA,
      generally, is beneficial for peer relations in children aged 11.

PMID- 29183955
TI  - Association between psychosocial work conditions and latent alcohol consumption
      trajectories among men and women over a 16-year period in a national Canadian
      sample.
AB  - BACKGROUND: It is unclear how psychosocial working conditions influence future
      alcohol consumption. Using group-based trajectory modelling, this study aimed to
      determine: the number of latent alcohol consumption trajectories over 16 years in
      a representative sample of the Canadian workforce; the association between
      psychosocial working conditions and longitudinal alcohol consumption; and if the
      association between psychosocial work factors and longitudinal alcohol
      consumption differed among men and women. METHODS: We included 5458 employed
      adults from the longitudinal Canadian National Population Health Survey. Average
      daily alcohol consumption was measured every 2 years from 1994 to 2010.
      Psychosocial work factors were measured in 1994 using the Job Content
      Questionnaire. Group-based trajectory modelling was used to derive the
      appropriate number of alcohol behaviour trajectories. The association between
      psychosocial work factors and alcohol trajectory membership was estimated using
      multinomial logistic regression. Models were stratified by sex to determine if
      these associations differed among men and women. RESULTS: Three alcohol
      consumption trajectories were present: non-drinkers, light drinkers (0.5-1
      drinks/day) and moderate drinkers (2-3 drinks/day). Higher workplace physical
      exertion and lower social support levels were associated with membership in the
      moderate drinking trajectory. Among men, lower psychological demands and higher
      physical exertion levels were associated with membership in the moderate drinking
      trajectory. Among women, lower levels of physical exertion were associated with
      membership in the light drinking trajectory, and higher psychological demand
      levels were associated with membership in the moderate drinking trajectory.
      CONCLUSIONS: Our study suggests that workplace physical exertion and
      psychological demands may be associated with different alcohol consumption
      trajectories among men and women.

PMID- 29183956
TI  - Generalisability of an online randomised controlled trial: an empirical analysis.
AB  - BACKGROUND: Investigators increasingly use online methods to recruit participants
      for randomised controlled trials (RCTs). However, the extent to which
      participants recruited online represent populations of interest is unknown. We
      evaluated how generalisable an online RCT sample is to men who have sex with men
      in China. METHODS: Inverse probability of sampling weights (IPSW) and the G
      formula were used to examine the generalisability of an online RCT using model
      based approaches. Online RCT data and national cross-sectional study data from
      China were analysed to illustrate the process of quantitatively assessing
      generalisability. The RCT (identifier NCT02248558) randomly assigned participants
      to a crowdsourced or health marketing video for promotion of HIV testing. The
      primary outcome was self-reported HIV testing within 4 weeks, with a non
      inferiority margin of -3%. RESULTS: In the original online RCT analysis, the
      estimated difference in proportions of HIV tested between the two arms
      (crowdsourcing and health marketing) was 2.1% (95% CI, -5.4% to 9.7%). The
      hypothesis that the crowdsourced video was not inferior to the health marketing
      video to promote HIV testing was not demonstrated. The IPSW and G-formula
      estimated differences were -2.6% (95% CI, -14.2 to 8.9) and 2.7% (95% CI, -10.7
      to 16.2), with both approaches also not establishing non-inferiority.
      CONCLUSIONS: Conducting generalisability analysis of an online RCT is feasible.
      Examining the generalisability of online RCTs is an important step before an
      intervention is scaled up. TRIAL REGISTRATION NUMBER: NCT02248558.

PMID- 29183957
TI  - Marriage and risk of dementia: systematic review and meta-analysis of
      observational studies.
AB  - BACKGROUND: Being married is associated with healthier lifestyle behaviours and
      lower mortality and may reduce risk for dementia due to life-course factors. We
      conducted a systematic review and meta-analysis of studies of the association
      between marital status and the risk of developing dementia. METHODS: We searched
      medical databases and contacted experts in the field for relevant studies
      reporting the relationship, adjusted for age and sex, between marital status and
      dementia. We rated methodological quality and conducted random-effects meta
      analyses to summarise relative risks of being widowed, divorced or lifelong
      single, compared with being married. Secondary stratified analyses with meta
      regression examined the impact of clinical and social context and study
      methodology on findings. RESULTS: We included 15 studies with 812 047
      participants. Compared with those who are married, lifelong single (relative
      risk=1.42 (95% CI 1.07 to 1.90)) and widowed (1.20 (1.02 to 1.41)) people have
      elevated risk of dementia. We did not find an association in divorced
      people.Further analyses showed that less education partially confounds the risk
      in widowhood and worse physical health the elevated risk in lifelong single
      people. Compared with studies that used clinical registers for ascertaining
      dementia diagnoses, those which clinically examined all participants found higher
      risk for being unmarried. CONCLUSIONS: Being married is associated with reduced
      risk of dementia than widowed and lifelong single people, who are also
      underdiagnosed in routine clinical practice. Dementia prevention in unmarried
      people should focus on education and physical health and should consider the
      possible effect of social engagement as a modifiable risk factor.

PMID- 29183958
TI  - Marriage and risk of dementia: systematic review and meta-analysis of
      observational studies.

PMID- 29183959
TI  - Stereotactic EEG-guided laser interstitial thermal therapy for mesial temporal
      lobe epilepsy.
AB  - OBJECTIVE: To determine the outcomes of combined stereo-electroencephalography
      guided and MRI-guided stereotactic laser interstitial thermal therapy (LITT) in
      the treatment of patients with drug-resistant mesial temporal lobe epilepsy
      (mTLE). METHODS: We prospectively assessed the surgical and neuropsychological
      outcomes in 21 patients with medically refractory mTLE who underwent LITT at the
      University of Chicago Medical Center. We further compared the surgical outcomes
      in patients with and without mesial temporal sclerosis (MTS). RESULTS: Of the 21
      patients, 19 (90%) underwent Invasive EEG study and 11 (52%) achieved freedom
      from disabling seizures with a mean duration of postoperative follow-up of 24+/
      11 months after LITT. Eight (73%) of 11 patients with MTS achieved freedom from
      disabling seizures, whereas 3 (30 %) of 10 patients without MTS achieved freedom
      from disabling seizures. Patients with MTS were significantly more likely to
      become seizure-free, as compared with those without MTS (P=0.002). There was no
      significant difference in total ablation volume and the percentage of the ablated
      amygdalohippocampal complex between seizure-free and non-seizure-free patients.
      Presurgical and postsurgical neuropsychological assessments were obtained in 10
      of 21 patients. While there was no group decline in any neuropsychological
      assessment, a significant postoperative decline in verbal memory and
      confrontational naming was observed in individual patients. CONCLUSIONS: MRI
      guided LITT is a safe and effective alternative to selective
      amygdalohippocampectomy and anterior temporal lobectomy for mTLE with MTS.
      Nevertheless, its efficacy in those without MTS seems modest. Large multicentre
      and prospective studies are warranted to further determine the efficacy and
      safety of LITT.

PMID- 29183960
TI  - Radium-223 Safety, Efficacy, and Concurrent Use with Abiraterone or Enzalutamide:
      First U.S. Experience from an Expanded Access Program.
AB  - BACKGROUND: In the phase III ALSYMPCA trial, metastatic castration-resistant
      prostate cancer (mCRPC) patients had few prior life-prolonging therapies.
      Following ALSYMPCA, which demonstrated radium-223 survival benefit, and before
      radium-223 U.S. commercial availability, an expanded access program (EAP)
      providing early-access radium-223 allowed life-prolonging therapies in current
      use. SUBJECTS, MATERIALS, AND METHODS: This phase II, open-label, single-arm,
      multicenter U.S. EAP (NCT01516762) enrolled patients with symptomatic mCRPC, >=2
      bone metastases, and no lung, liver, or brain metastases. Patients received
      radium-223 55 kBq/kg intravenously every 4 weeks * 6. Primary outcomes were acute
      and long-term safety. Additional analyses were done by number of radium-223
      injections, and prior or concomitant abiraterone or enzalutamide use. RESULTS: Of
      252 patients, 184 received radium-223: 165/184 (90%) had Eastern Cooperative
      Oncology Group (ECOG) performance status 0-1; 183 (99%) had prior systemic
      anticancer therapy. Treatment-related adverse events occurred in 93/184 (51%)
      patients during treatment and 11 (6%) during follow-up. Median overall survival
      was 17 months, with 134/184 (73%) patients censored because of short follow-up
      due to radium-223 approval. In post hoc analyses, patients with >=3 prior
      anticancer medications, baseline ECOG performance status >=2, and lower baseline
      hemoglobin were less likely to receive 5-6 radium-223 injections and unlikely to
      benefit from radium-223. Radium-223 was well tolerated regardless of concurrent
      or prior abiraterone or enzalutamide. CONCLUSION: Radium-223 was well tolerated,
      with no new safety concerns; safety was maintained with abiraterone or
      enzalutamide. Patients with more advanced disease were less likely to benefit
      from radium-223. Clinicians should consider baseline characteristics and therapy
      sequence for greatest clinical value. IMPLICATIONS FOR PRACTICE: In this phase II
      U.S. expanded access program, radium-223 was well tolerated, with a median
      overall survival of 17 months in metastatic castration-resistant prostate cancer
      patients. In post hoc analyses, radium-223 was safe regardless of concurrent
      abiraterone or enzalutamide, and median overall survival appeared longer when
      radium-223 was used earlier in patients with less prior treatment. Patients with
      more advanced disease were less likely to benefit from radium-223. Clinicians
      should consider baseline clinical characteristics and therapy sequence to provide
      the greatest clinical value to patients.

PMID- 29183962
TI  - Intestinal lymphatic HDL miR-223 and ApoA-I are reduced during insulin resistance
      and restored with niacin.
AB  - The intestine is involved in whole-body lipid and cholesterol homeostasis and
      secretes lipoproteins containing apolipoprotein (Apo)B48 and discrete ApoA-I into
      the mesenteric lymph. The lymphatic system has been proposed to have a
      significant role in the reverse cholesterol transport pathway associated with HDL
      ApoA-I. In conditions of insulin resistance (IR), there is intestinal
      overproduction of chylomicrons containing ApoB48; however, there is limited data
      on the intestinal synthesis and secretion of HDL-ApoA-I. microRNA (miR)-223 has
      been shown to regulate peripheral HDL metabolism and may impact intestinal
      derived HDL. Niacin (nicotinic acid; vitamin B3) is known to regulate lipid
      metabolism, but the role of niacin in modulating intestinal lipid and lipoprotein
      (ApoB48 and ApoA-I) metabolism is unknown. The aim of this study was to determine
      the secretion of intestinal lymphatic HDL-ApoA-I and the effect of dietary
      intervention with niacin on these pathways in a rodent model of IR. HDL was
      isolated from intestinal mesenteric lymph by density ultracentrifugation, and
      subsequent HDL miR analysis was developed in collaboration with Exiqon Services.
      Insulin-resistant rodents were fed chow or chow with niacin (1% w/w) for 6 wk.
      Intestinal lymph HDL-ApoA-I and miR-223 expression were lower by at least 45 and
      60%, respectively, and lymph HDL was associated with 85% higher triglyceride (TG)
      content in IR compared to non-IR control group. Niacin was found to increase
      secretion of lymph HDL and miR-223 by at least 50-60% and to deplete the TGs
      associated with HDL compared with the nontreated IR group. Niacin significantly
      increased peroxisome proliferator-activating nuclear receptor alpha and carnitine
      palmitoyltransferase I alpha mRNA and annulled Tnf-alpha mRNA expression in
      intestinal (jejunal) explants. Altered intestinal lymphatic HDL-ApoA-I and miR
      223 metabolism in IR and modulation by niacin may provide insight into the
      intestinal-mediated regulation of the reverse cholesterol transport pathway.
      Mangat, R., Borthwick, F., Haase, T., Jacome, M., Nelson, R., Kontush, A., Vine,
      D. F., Proctor, S. D. Intestinal lymphatic HDL miR-223 and ApoA-I are reduced
      during insulin resistance and restored with niacin.

PMID- 29183961
TI  - Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic
      review, network meta-analysis, and cost effectiveness analysis.
AB  - Objective To compare the efficacy, safety, and cost effectiveness of direct
      acting oral anticoagulants (DOACs) for patients with atrial fibrillation.Design
      Systematic review, network meta-analysis, and cost effectiveness analysis. Data
      sources Medline, PreMedline, Embase, and The Cochrane Library.Eligibility
      criteria for selecting studies Published randomised trials evaluating the use of
      a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in
      patients with atrial fibrillation.Results 23 randomised trials involving 94 656
      patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a
      target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence
      interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81),
      edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily
      (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared
      with warfarin. The risk of stroke or systemic embolism was higher with edoxaban
      60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35,
      1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause
      mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily
      (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93),
      edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily
      (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin.
      The risk of major bleeding was higher with dabigatran 150 mg twice daily than
      apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily
      than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice
      daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of
      intracranial bleeding was substantially lower for most DOACs compared with
      warfarin, whereas the risk of gastrointestinal bleeding was higher with some
      DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most
      outcomes, and was cost effective compared with warfarin.Conclusions The network
      meta-analysis informs the choice of DOACs for prevention of stroke in patients
      with atrial fibrillation. Several DOACs are of net benefit compared with
      warfarin. A trial directly comparing DOACs would overcome the need for indirect
      comparisons to be made through network meta-analysis.Systematic review
      registration PROSPERO CRD 42013005324.

PMID- 29183963
TI  - Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a
      pH optimum for intercellular communication.
AB  - Most mammalian cells can intercommunicate via connexin-assembled, gap-junctional
      channels. To regulate signal transmission, connexin (Cx) channel permeability
      must respond dynamically to physiological and pathophysiological stimuli. One key
      stimulus is intracellular pH (pHi), which is modulated by a tissue's metabolic
      and perfusion status. Our understanding of the molecular mechanism of H+ gating
      of Cx43 channels-the major isoform in the heart and brain-is incomplete. To
      interrogate the effects of acidic and alkaline pHi on Cx43 channels, we combined
      voltage-clamp electrophysiology with pHi imaging and photolytic H+ uncaging,
      performed over a range of pHi values. We demonstrate that Cx43 channels expressed
      in HeLa or N2a cell pairs are gated biphasically by pHi via a process that
      consists of activation by H+ ions at alkaline pHi and inhibition at more acidic
      pHi. For Cx43 channel-mediated solute/ion transmission, the ensemble of these
      effects produces a pHi optimum, near resting pHi. By using Cx43 mutants, we
      demonstrate that alkaline gating involves cysteine residues of the C terminus and
      is independent of motifs previously implicated in acidic gating. Thus, we present
      a molecular mechanism by which cytoplasmic acid-base chemistry fine tunes
      intercellular communication and establishes conditions for the optimal
      transmission of solutes and signals in tissues, such as the heart and brain.
      Garciarena, C. D., Malik, A., Swietach, P., Moreno, A. P., Vaughan-Jones, R. D.
      Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a
      pH optimum for intercellular communication.

PMID- 29183964
TI  - Regulation of blood-testis barrier assembly in vivo by germ cells.
AB  - The assembly of the blood-testis barrier (BTB) during postnatal development is
      crucial to support meiosis. However, the role of germ cells in BTB assembly
      remains unclear. Herein, KitW/KitWV mice were used as a study model. These mice
      were infertile, failing to establish a functional BTB to support meiosis due to c
      Kit mutation. Transplantation of undifferentiated spermatogonia derived from
      normal mice into the testis of KitW/KitWV mice triggered functional BTB assembly,
      displaying cyclic remodeling during the epithelial cycle. Also, transplanted germ
      cells were capable of inducing Leydig cell testosterone production, which could
      enhance the expression of integral membrane protein claudin 3 in Sertoli cells.
      Early spermatocytes were shown to play a vital role in directing BTB assembly by
      expressing claudin 3, which likely created a transient adhesion structure to
      mediate BTB and cytoskeleton assembly in adjacent Sertoli cells. In summary, the
      positive modulation of germ cells on somatic cell function provides useful
      information regarding somatic-germ cell interactions.-Li, X.-Y., Zhang, Y., Wang,
      X.-X., Jin, C., Wang, Y.-Q., Sun, T.-C., Li, J., Tang, J.-X., Batool, A., Deng,
      S.-L., Chen, S.-R., Cheng, C. Y., Liu, Y.-X. Regulation of blood-testis barrier
      assembly in vivo by germ cells.

PMID- 29183965
TI  - Regulation of proinflammatory monocyte activation by the kynurenine-AhR axis
      underlies immunometabolic control of depressive behavior in mice.
AB  - Elevated kynurenine (Kyn) production from tryptophan (Trp) metabolism is a
      biomarker of immune dysregulation in depression, but its mechanistic
      contributions to the behavioral symptoms are poorly defined. In this study, Kyn
      was shown to be a metabolic regulator of proinflammatory monocytes that
      orchestrated peripheral immune activation and neuroinflammation in depressive
      mice. Kyn-induced depressive behavior was paralleled by brain infiltration of
      proinflammatory monocytes and astrocytic activation. Kyn enhanced chemokine (C-C
      motif) ligand-2-mediated chemotaxis of monocytes and their proinflammatory
      capability on cocultured astrocytes in vitro, which involved the activation of
      aryl hydrocarbon receptor (AhR) signaling. Kyn augmented, whereas pharmacological
      AhR blockade rescued, systemic inflammation-induced monocyte trafficking,
      neuroimmune disturbance, and depressive-like behavior in mice. The behavior
      exacerbating effects of the Kyn-AhR axis were dampened with prior depletion of
      functional monocytes in the periphery. The findings in our study extend
      understanding of an immunologic effect of Kyn that links Trp metabolism and
      inflammatory signaling in depression pathology, with potential therapeutic
      implications for depressive disorders.-Zang, X., Zheng, X., Hou, Y., Hu, M.,
      Wang, H., Bao, X., Zhou, F., Wang, G., Hao, H. Regulation of proinflammatory
      monocyte activation by the kynurenine-AhR axis underlies immunometabolic control
      of depressive behavior in mice.

PMID- 29183966
TI  - Equilibration of energy in slow-fast systems.
AB  - Ergodicity is a fundamental requirement for a dynamical system to reach a state
      of statistical equilibrium. However, in systems with several characteristic
      timescales, the ergodicity of the fast subsystem impedes the equilibration of the
      whole system because of the presence of an adiabatic invariant. In this paper, we
      show that violation of ergodicity in the fast dynamics can drive the whole system
      to equilibrium. To show this principle, we investigate the dynamics of springy
      billiards, which are mechanical systems composed of a small particle bouncing
      elastically in a bounded domain, where one of the boundary walls has finite mass
      and is attached to a linear spring. Numerical simulations show that the springy
      billiard systems approach equilibrium at an exponential rate. However, in the
      limit of vanishing particle-to-wall mass ratio, the equilibration rates remain
      strictly positive only when the fast particle dynamics reveal two or more ergodic
      components for a range of wall positions. For this case, we show that the slow
      dynamics of the moving wall can be modeled by a random process. Numerical
      simulations of the corresponding springy billiards and their random models show
      equilibration with similar positive rates.

PMID- 29183967
TI  - Using deep learning and Google Street View to estimate the demographic makeup of
      neighborhoods across the United States.
AB  - The United States spends more than $250 million each year on the American
      Community Survey (ACS), a labor-intensive door-to-door study that measures
      statistics relating to race, gender, education, occupation, unemployment, and
      other demographic factors. Although a comprehensive source of data, the lag
      between demographic changes and their appearance in the ACS can exceed several
      years. As digital imagery becomes ubiquitous and machine vision techniques
      improve, automated data analysis may become an increasingly practical supplement
      to the ACS. Here, we present a method that estimates socioeconomic
      characteristics of regions spanning 200 US cities by using 50 million images of
      street scenes gathered with Google Street View cars. Using deep learning-based
      computer vision techniques, we determined the make, model, and year of all motor
      vehicles encountered in particular neighborhoods. Data from this census of motor
      vehicles, which enumerated 22 million automobiles in total (8% of all automobiles
      in the United States), were used to accurately estimate income, race, education,
      and voting patterns at the zip code and precinct level. (The average US precinct
      contains ~1,000 people.) The resulting associations are surprisingly simple and
      powerful. For instance, if the number of sedans encountered during a drive
      through a city is higher than the number of pickup trucks, the city is likely to
      vote for a Democrat during the next presidential election (88% chance);
      otherwise, it is likely to vote Republican (82%). Our results suggest that
      automated systems for monitoring demographics may effectively complement labor
      intensive approaches, with the potential to measure demographics with fine
      spatial resolution, in close to real time.

PMID- 29183969
TI  - Relationship of tropospheric stability to climate sensitivity and Earth's
      observed radiation budget.
AB  - Climate feedbacks generally become smaller in magnitude over time under CO2
      forcing in coupled climate models, leading to an increase in the effective
      climate sensitivity, the estimated global-mean surface warming in steady state
      for doubled CO2 Here, we show that the evolution of climate feedbacks in models
      is consistent with the effect of a change in tropospheric stability, as has
      recently been hypothesized, and the latter is itself driven by the evolution of
      the pattern of sea-surface temperature response. The change in climate feedback
      is mainly associated with a decrease in marine tropical low cloud (a more
      positive shortwave cloud feedback) and with a less negative lapse-rate feedback,
      as expected from a decrease in stability. Smaller changes in surface albedo and
      humidity feedbacks also contribute to the overall change in feedback, but are
      unexplained by stability. The spatial pattern of feedback changes closely matches
      the pattern of stability changes, with the largest increase in feedback occurring
      in the tropical East Pacific. Relationships qualitatively similar to those in the
      models among sea-surface temperature pattern, stability, and radiative budget are
      also found in observations on interannual time scales. Our results suggest that
      constraining the future evolution of sea-surface temperature patterns and
      tropospheric stability will be necessary for constraining climate sensitivity.

PMID- 29183968
TI  - Catch bond drives stator mechanosensitivity in the bacterial flagellar motor.
AB  - The bacterial flagellar motor (BFM) is the rotary motor that rotates each
      bacterial flagellum, powering the swimming and swarming of many motile bacteria.
      The torque is provided by stator units, ion motive force-powered ion channels
      known to assemble and disassemble dynamically in the BFM. This turnover is
      mechanosensitive, with the number of engaged units dependent on the viscous load
      experienced by the motor through the flagellum. However, the molecular mechanism
      driving BFM mechanosensitivity is unknown. Here, we directly measure the kinetics
      of arrival and departure of the stator units in individual motors via analysis of
      high-resolution recordings of motor speed, while dynamically varying the load on
      the motor via external magnetic torque. The kinetic rates obtained, robust with
      respect to the details of the applied adsorption model, indicate that the
      lifetime of an assembled stator unit increases when a higher force is applied to
      its anchoring point in the cell wall. This provides strong evidence that a catch
      bond (a bond strengthened instead of weakened by force) drives mechanosensitivity
      of the flagellar motor complex. These results add the BFM to a short, but
      growing, list of systems demonstrating catch bonds, suggesting that this
      "molecular strategy" is a widespread mechanism to sense and respond to mechanical
      stress. We propose that force-enhanced stator adhesion allows the cell to adapt
      to a heterogeneous environmental viscosity and may ultimately play a role in
      surface-sensing during swarming and biofilm formation.

PMID- 29183971
TI  - Inequality in nature and society.
AB  - Most societies are economically dominated by a small elite, and similarly,
      natural communities are typically dominated by a small fraction of the species.
      Here we reveal a strong similarity between patterns of inequality in nature and
      society, hinting at fundamental unifying mechanisms. We show that chance alone
      will drive 1% or less of the community to dominate 50% of all resources in
      situations where gains and losses are multiplicative, as in returns on assets or
      growth rates of populations. Key mechanisms that counteract such hyperdominance
      include natural enemies in nature and wealth-equalizing institutions in society.
      However, historical research of European developments over the past millennium
      suggests that such institutions become ineffective in times of societal
      upscaling. A corollary is that in a globalizing world, wealth will inevitably be
      appropriated by a very small fraction of the population unless effective wealth
      equalizing institutions emerge at the global level.

PMID- 29183972
TI  - Unleashing meiotic crossovers in hybrid plants.
AB  - Meiotic crossovers shuffle parental genetic information, providing novel
      combinations of alleles on which natural or artificial selection can act.
      However, crossover events are relatively rare, typically one to three exchange
      points per chromosome pair. Recent work has identified three pathways limiting
      meiotic crossovers in Arabidopsis thaliana that rely on the activity of FANCM
      [Crismani W, et al. (2012) Science 336:1588-1590], RECQ4 [Seguela-Arnaud M, et
      al. (2015) Proc Natl Acad Sci USA 112:4713-4718], and FIGL1 [Girard C, et al.
      (2015) PLoS Genet 11:e1005369]. Here we analyzed recombination in plants in which
      one, two, or all three of these pathways were disrupted in both pure line and
      hybrid contexts. The greatest effect was observed when combining recq4 and figl1
      mutations, which increased the hybrid genetic map length from 389 to 3,037 cM.
      This corresponds to an unprecedented 7.8-fold increase in crossover frequency.
      Disrupting the three pathways did not further increase recombination, suggesting
      that some upper limit had been reached. The increase in crossovers is not uniform
      along chromosomes and rises from centromere to telomere. Finally, although in
      wild type recombination is much higher in male meiosis than in female meiosis
      (490 cM vs. 290 cM), female recombination is higher than male recombination in
      recq4 figl1 (3,200 cM vs. 2,720 cM), suggesting that the factors that make wild
      type female meiosis less recombinogenic than male wild-type meiosis do not apply
      in the mutant context. The massive increase in recombination observed in recq4
      figl1 hybrids opens the possibility of manipulating recombination to enhance
      plant breeding efficiency.

PMID- 29183970
TI  - Patterns of coevolving amino acids unveil structural and dynamical domains.
AB  - Patterns of interacting amino acids are so preserved within protein families that
      the sole analysis of evolutionary comutations can identify pairs of contacting
      residues. It is also known that evolution conserves functional dynamics, i.e.,
      the concerted motion or displacement of large protein regions or domains. Is it,
      therefore, possible to use a pure sequence-based analysis to identify these
      dynamical domains? To address this question, we introduce here a general
      coevolutionary coupling analysis strategy and apply it to a curated sequence
      database of hundreds of protein families. For most families, the sequence-based
      method partitions amino acids into a few clusters. When viewed in the context of
      the native structure, these clusters have the signature characteristics of viable
      protein domains: They are spatially separated but individually compact. They have
      a direct functional bearing too, as shown for various reference cases. We
      conclude that even large-scale structural and functionally related properties can
      be recovered from inference methods applied to evolutionary-related sequences.
      The method introduced here is available as a software package and web server
      (spectrus.sissa.it/spectrus-evo_webserver).

PMID- 29183973
TI  - On the role of the corpus callosum in interhemispheric functional connectivity in
      humans.
AB  - Resting state functional connectivity is defined in terms of temporal
      correlations between physiologic signals, most commonly studied using functional
      magnetic resonance imaging. Major features of functional connectivity correspond
      to structural (axonal) connectivity. However, this relation is not one-to-one.
      Interhemispheric functional connectivity in relation to the corpus callosum
      presents a case in point. Specifically, several reports have documented nearly
      intact interhemispheric functional connectivity in individuals in whom the corpus
      callosum (the major commissure between the hemispheres) never develops. To
      investigate this question, we assessed functional connectivity before and after
      surgical section of the corpus callosum in 22 patients with medically refractory
      epilepsy. Section of the corpus callosum markedly reduced interhemispheric
      functional connectivity. This effect was more profound in multimodal associative
      areas in the frontal and parietal lobe than primary regions of sensorimotor and
      visual function. Moreover, no evidence of recovery was observed in a limited
      sample in which multiyear, longitudinal follow-up was obtained. Comparison of
      partial vs. complete callosotomy revealed several effects implying the existence
      of polysynaptic functional connectivity between remote brain regions. Thus, our
      results demonstrate that callosal as well as extracallosal anatomical connections
      play a role in the maintenance of interhemispheric functional connectivity.

PMID- 29183974
TI  - Spin susceptibility of charge-ordered YBa2Cu3O y across the upper critical field.
AB  - The value of the upper critical field Hc2, a fundamental characteristic of the
      superconducting state, has been subject to strong controversy in high-Tc copper
      oxides. Since the issue has been tackled almost exclusively by macroscopic
      techniques so far, there is a clear need for local-probe measurements. Here, we
      use 17O NMR to measure the spin susceptibility [Formula: see text] of the CuO2
      planes at low temperature in charge-ordered YBa2Cu3O y We find that [Formula: see
      text] increases (most likely linearly) with magnetic field H and saturates above
      field values ranging from 20 T to 40 T. This result is consistent with the lowest
      Hc2 values claimed previously and with the interpretation that the charge density
      wave (CDW) reduces Hc2 in underdoped YBa2Cu3O y Furthermore, the absence of
      marked deviation in [Formula: see text] at the onset of long-range CDW order
      indicates that this [Formula: see text] reduction and the Fermi-surface
      reconstruction are primarily rooted in the short-range CDW order already present
      in zero field, not in the field-induced long-range CDW order. Above [Formula: see
      text], the relatively low values of [Formula: see text] at [Formula: see text] K
      show that the pseudogap is a ground-state property, independent of the
      superconducting gap.

PMID- 29183975
TI  - High-resolution mapping of cis-regulatory variation in budding yeast.
AB  - Genetic variants affecting gene-expression levels are a major source of
      phenotypic variation. The approximate locations of these variants can be mapped
      as expression quantitative trait loci (eQTLs); however, a major limitation of
      eQTLs is their low resolution, which precludes investigation of the causal
      variants and their molecular mechanisms. Here we report RNA-seq and full genome
      sequences for 85 diverse isolates of the yeast Saccharomyces cerevisiae-including
      wild, domesticated, and human clinical strains-which allowed us to perform eQTL
      mapping with 50-fold higher resolution than previously possible. In addition to
      variants in promoters, we uncovered an important role for variants in 3'UTRs,
      especially those affecting binding of the PUF family of RNA-binding proteins. The
      eQTLs are predominantly under negative selection, particularly those affecting
      essential genes and conserved genes. However, applying the sign test for lineage
      specific selection revealed the polygenic up-regulation of dozens of biofilm
      suppressor genes in strains isolated from human patients, consistent with the key
      role of biofilms in fungal pathogenicity. In addition, a single variant in the
      promoter of a biofilm suppressor, NIT3, showed the strongest genome-wide
      association with clinical origin. Altogether, our results demonstrate the power
      of high-resolution eQTL mapping in understanding the molecular mechanisms of
      regulatory variation, as well as the natural selection acting on this variation
      that drives adaptation to environments, ranging from laboratories to vineyards to
      the human body.

PMID- 29183976
TI  - Rapid adaptive evolution in novel environments acts as an architect of population
      range expansion.
AB  - Colonization and expansion into novel landscapes determine the distribution and
      abundance of species in our rapidly changing ecosystems worldwide. Colonization
      events are crucibles for rapid evolution, but it is not known whether
      evolutionary changes arise mainly after successful colonization has occurred, or
      if evolution plays an immediate role, governing the growth and expansion speed of
      colonizing populations. There is evidence that spatial evolutionary processes can
      speed range expansion within a few generations because dispersal tendencies may
      evolve upwards at range edges. Additionally, rapid adaptation to a novel
      environment can increase population growth rates, which also promotes spread.
      However, the role of adaptive evolution and the relative contributions of spatial
      evolution and adaptation to expansion are unclear. Using a model system, red
      flour beetles (Tribolium castaneum), we either allowed or constrained evolution
      of populations colonizing a novel environment and measured population growth and
      spread. At the end of the experiment we assessed the fitness and dispersal
      tendency of individuals originating either from the core or edge of evolving
      populations or from nonevolving populations in a common garden. Within six
      generations, evolving populations grew three times larger and spread 46% faster
      than populations in which evolution was constrained. Increased size and expansion
      speed were strongly driven by adaptation, whereas spatial evolutionary processes
      acting on edge subpopulations contributed less. This experimental evidence
      demonstrates that rapid evolution drives both population growth and expansion
      speed and is thus crucial to consider for managing biological invasions and
      successfully introducing or reintroducing species for management and
      conservation.

PMID- 29183977
TI  - Osmosensing by the bacterial PhoQ/PhoP two-component system.
AB  - The PhoQ/PhoP two-component system plays an essential role in the response of
      enterobacteria to the environment of their mammalian hosts. It is known to sense
      several stimuli that are potentially associated with the host, including
      extracellular magnesium limitation, low pH, and the presence of cationic
      antimicrobial peptides. Here, we show that the PhoQ/PhoP two-component systems of
      Escherichia coli and Salmonella can also perceive an osmotic upshift, another key
      stimulus to which bacteria become exposed within the host. In contrast to most
      previously established stimuli of PhoQ, the detection of osmotic upshift does not
      require its periplasmic sensor domain. Instead, we show that the activity of PhoQ
      is affected by the length of the transmembrane (TM) helix as well as by membrane
      lateral pressure. We therefore propose that osmosensing relies on a
      conformational change within the TM domain of PhoQ induced by a perturbation in
      cell membrane thickness and lateral pressure under hyperosmotic conditions.
      Furthermore, the response mediated by the PhoQ/PhoP two-component system was
      found to improve bacterial growth recovery under hyperosmotic stress, partly
      through stabilization of the sigma factor RpoS. Our findings directly link the
      PhoQ/PhoP two-component system to bacterial osmosensing, suggesting that this
      system can mediate a concerted response to most of the established host-related
      cues.

PMID- 29183978
TI  - Proteomics of phosphorylation and protein dynamics during fertilization and
      meiotic exit in the Xenopus egg.
AB  - Fertilization releases the meiotic arrest and initiates the events that prepare
      the egg for the ensuing developmental program. Protein degradation and
      phosphorylation are known to regulate protein activity during this process.
      However, the full extent of protein loss and phosphoregulation is still unknown.
      We examined absolute protein and phosphosite dynamics of the fertilization
      response by mass spectrometry-based proteomics in electroactivated eggs. To do
      this, we developed an approach for calculating the stoichiometry of phosphosites
      from multiplexed proteomics that is compatible with dynamic, stable, and
      multisite phosphorylation. Overall, the data suggest that degradation is limited
      to a few low-abundance proteins. However, this degradation promotes extensive
      dephosphorylation that occurs over a wide range of abundances during meiotic
      exit. We also show that eggs release a large amount of protein into the medium
      just after fertilization, most likely related to the blocks to polyspermy.
      Concomitantly, there is a substantial increase in phosphorylation likely tied to
      calcium-activated kinases. We identify putative degradation targets and
      components of the slow block to polyspermy. The analytical approaches
      demonstrated here are broadly applicable to studies of dynamic biological
      systems.

PMID- 29183979
TI  - Vasopressin excites interneurons to suppress hippocampal network activity across
      a broad span of brain maturity at birth.
AB  - During birth in mammals, a pronounced surge of fetal peripheral stress hormones
      takes place to promote survival in the transition to the extrauterine
      environment. However, it is not known whether the hormonal signaling involves
      central pathways with direct protective effects on the perinatal brain. Here, we
      show that arginine vasopressin specifically activates interneurons to suppress
      spontaneous network events in the perinatal hippocampus. Experiments done on the
      altricial rat and precocial guinea pig neonate demonstrated that the effect of
      vasopressin is not dependent on the level of maturation (depolarizing vs.
      hyperpolarizing) of postsynaptic GABAA receptor actions. Thus, the fetal
      mammalian brain is equipped with an evolutionarily conserved mechanism well
      suited to suppress energetically expensive correlated network events under
      conditions of reduced oxygen supply at birth.

PMID- 29183980
TI  - Speaker gaze increases information coupling between infant and adult brains.
AB  - When infants and adults communicate, they exchange social signals of availability
      and communicative intention such as eye gaze. Previous research indicates that
      when communication is successful, close temporal dependencies arise between adult
      speakers' and listeners' neural activity. However, it is not known whether
      similar neural contingencies exist within adult-infant dyads. Here, we used dual
      electroencephalography to assess whether direct gaze increases neural coupling
      between adults and infants during screen-based and live interactions. In
      experiment 1 (n = 17), infants viewed videos of an adult who was singing nursery
      rhymes with (i) direct gaze (looking forward), (ii) indirect gaze (head and eyes
      averted by 20 degrees ), or (iii) direct-oblique gaze (head averted but eyes
      orientated forward). In experiment 2 (n = 19), infants viewed the same adult in a
      live context, singing with direct or indirect gaze. Gaze-related changes in adult
      infant neural network connectivity were measured using partial directed
      coherence. Across both experiments, the adult had a significant (Granger) causal
      influence on infants' neural activity, which was stronger during direct and
      direct-oblique gaze relative to indirect gaze. During live interactions, infants
      also influenced the adult more during direct than indirect gaze. Further, infants
      vocalized more frequently during live direct gaze, and individual infants who
      vocalized longer also elicited stronger synchronization from the adult. These
      results demonstrate that direct gaze strengthens bidirectional adult-infant
      neural connectivity during communication. Thus, ostensive social signals could
      act to bring brains into mutual temporal alignment, creating a joint-networked
      state that is structured to facilitate information transfer during early
      communication and learning.

PMID- 29183981
TI  - Robust zero resistance in a superconducting high-entropy alloy at pressures up to
      190 GPa.
AB  - We report the observation of extraordinarily robust zero-resistance
      superconductivity in the pressurized (TaNb)0.67(HfZrTi)0.33 high-entropy alloy--a
      material with a body-centered-cubic crystal structure made from five randomly
      distributed transition-metal elements. The transition to superconductivity (TC )
      increases from an initial temperature of 7.7 K at ambient pressure to 10 K at ~60
      GPa, and then slowly decreases to 9 K by 190.6 GPa, a pressure that falls within
      that of the outer core of the earth. We infer that the continuous existence of
      the zero-resistance superconductivity from 1 atm up to such a high pressure
      requires a special combination of electronic and mechanical characteristics. This
      high-entropy alloy superconductor thus may have a bright future for applications
      under extreme conditions, and also poses a challenge for understanding the
      underlying quantum physics.

PMID- 29183982
TI  - Improved detection of synthetic lethal interactions in Drosophila cells using
      variable dose analysis (VDA).
AB  - Synthetic sick or synthetic lethal (SS/L) screens are a powerful way to identify
      candidate drug targets to specifically kill tumor cells, but this approach
      generally suffers from low consistency between screens. We found that many SS/L
      interactions involve essential genes and are therefore detectable within a
      limited range of knockdown efficiency. Such interactions are often missed by
      overly efficient RNAi reagents. We therefore developed an assay that measures
      viability over a range of knockdown efficiency within a cell population. This
      method, called Variable Dose Analysis (VDA), is highly sensitive to viability
      phenotypes and reproducibly detects SS/L interactions. We applied the VDA method
      to search for SS/L interactions with TSC1 and TSC2, the two tumor suppressors
      underlying tuberous sclerosis complex (TSC), and generated a SS/L network for
      TSC. Using this network, we identified four Food and Drug Administration-approved
      drugs that selectively affect viability of TSC-deficient cells, representing
      promising candidates for repurposing to treat TSC-related tumors.

PMID- 29183983
TI  - Precision genome editing using synthesis-dependent repair of Cas9-induced DNA
      breaks.
AB  - The RNA-guided DNA endonuclease Cas9 has emerged as a powerful tool for genome
      engineering. Cas9 creates targeted double-stranded breaks (DSBs) in the genome.
      Knockin of specific mutations (precision genome editing) requires homology
      directed repair (HDR) of the DSB by synthetic donor DNAs containing the desired
      edits, but HDR has been reported to be variably efficient. Here, we report that
      linear DNAs (single and double stranded) engage in a high-efficiency HDR
      mechanism that requires only ~35 nucleotides of homology with the targeted locus
      to introduce edits ranging from 1 to 1,000 nucleotides. We demonstrate the
      utility of linear donors by introducing fluorescent protein tags in human cells
      and mouse embryos using PCR fragments. We find that repair is local, polarity
      sensitive, and prone to template switching, characteristics that are consistent
      with gene conversion by synthesis-dependent strand annealing. Our findings enable
      rational design of synthetic donor DNAs for efficient genome editing.

PMID- 29183984
TI  - Unraveling the structure and chemical mechanisms of highly oxygenated
      intermediates in oxidation of organic compounds.
AB  - Decades of research on the autooxidation of organic compounds have provided
      fundamental and practical insights into these processes; however, the structure
      of many key autooxidation intermediates and the reactions leading to their
      formation still remain unclear. This work provides additional experimental
      evidence that highly oxygenated intermediates with one or more hydroperoxy groups
      are prevalent in the autooxidation of various oxygenated (e.g., alcohol,
      aldehyde, keto compounds, ether, and ester) and nonoxygenated (e.g., normal
      alkane, branched alkane, and cycloalkane) organic compounds. These findings
      improve our understanding of autooxidation reaction mechanisms that are routinely
      used to predict fuel ignition and oxidative stability of liquid hydrocarbons,
      while also providing insights relevant to the formation mechanisms of
      tropospheric aerosol building blocks. The direct observation of highly oxygenated
      intermediates for the autooxidation of alkanes at 500-600 K builds upon prior
      observations made in atmospheric conditions for the autooxidation of terpenes and
      other unsaturated hydrocarbons; it shows that highly oxygenated intermediates are
      stable at conditions above room temperature. These results further reveal that
      highly oxygenated intermediates are not only accessible by chemical activation
      but also by thermal activation. Theoretical calculations on H-atom migration
      reactions are presented to rationalize the relationship between the organic
      compound's molecular structure (n-alkane, branched alkane, and cycloalkane) and
      its propensity to produce highly oxygenated intermediates via extensive
      autooxidation of hydroperoxyalkylperoxy radicals. Finally, detailed chemical
      kinetic simulations demonstrate the influence of these additional reaction
      pathways on the ignition of practical fuels.

PMID- 29183986
TI  - New test for asthma will save NHS millions, says NICE.

PMID- 29183987
TI  - SpotLearn: Convolutional Neural Network for Detection of Fluorescence In Situ
      Hybridization (FISH) Signals in High-Throughput Imaging Approaches.
AB  - DNA fluorescence in situ hybridization (FISH) is the technique of choice to map
      the position of genomic loci in three-dimensional (3D) space at the single allele
      level in the cell nucleus. High-throughput DNA FISH methods have recently been
      developed using complex libraries of fluorescently labeled synthetic
      oligonucleotides and automated fluorescence microscopy, enabling large-scale
      interrogation of genomic organization. Although the FISH signals generated by
      high-throughput methods can, in principle, be analyzed by traditional spot
      detection algorithms, these approaches require user intervention to optimize each
      interrogated genomic locus, making analysis of tens or hundreds of genomic loci
      in a single experiment prohibitive. We report here the design and testing of two
      separate machine learning-based workflows for FISH signal detection in a high
      throughput format. The two methods rely on random forest (RF) classification or
      convolutional neural networks (CNNs), respectively. Both workflows detect DNA
      FISH signals with high accuracy in three separate fluorescence microscopy
      channels for tens of independent genomic loci, without the need for manual
      parameter value setting on a per locus basis. In particular, the CNN workflow,
      which we named SpotLearn, is highly efficient and accurate in the detection of
      DNA FISH signals with low signal-to-noise ratio (SNR). We suggest that SpotLearn
      will be useful to accurately and robustly detect diverse DNA FISH signals in a
      high-throughput fashion, enabling the visualization and positioning of hundreds
      of genomic loci in a single experiment.

PMID- 29183985
TI  - Metagenomics-guided analysis of microbial chemolithoautotrophic phosphite
      oxidation yields evidence of a seventh natural CO2 fixation pathway.
AB  - Dissimilatory phosphite oxidation (DPO), a microbial metabolism by which
      phosphite (HPO32-) is oxidized to phosphate (PO43-), is the most energetically
      favorable chemotrophic electron-donating process known. Only one DPO organism has
      been described to date, and little is known about the environmental relevance of
      this metabolism. In this study, we used 16S rRNA gene community analysis and
      genome-resolved metagenomics to characterize anaerobic wastewater treatment
      sludge enrichments performing DPO coupled to CO2 reduction. We identified an
      uncultivated DPO bacterium, Candidatus Phosphitivorax (Ca. P.) anaerolimi strain
      Phox-21, that belongs to candidate order GW-28 within the Deltaproteobacteria,
      which has no known cultured isolates. Genes for phosphite oxidation and for CO2
      reduction to formate were found in the genome of Ca. P. anaerolimi, but it
      appears to lack any of the known natural carbon fixation pathways. These
      observations led us to propose a metabolic model for autotrophic growth by Ca. P.
      anaerolimi whereby DPO drives CO2 reduction to formate, which is then assimilated
      into biomass via the reductive glycine pathway.

PMID- 29183988
TI  - Development and differentiation of early innate lymphoid progenitors.
AB  - Early innate lymphoid progenitors (EILPs) have recently been identified in mouse
      adult bone marrow as a multipotential progenitor population specified toward
      innate lymphoid cell (ILC) lineages, but their relationship with other described
      ILC progenitors is still unclear. In this study, we examine the progenitor
      successor relationships between EILPs, all-lymphoid progenitors (ALPs), and ILC
      precursors (ILCps). Functional, bioinformatic, phenotypical, and genetic
      approaches collectively establish EILPs as an intermediate progenitor between
      ALPs and ILCps. Our work additionally provides new candidate regulators of ILC
      development and clearly defines the stage of requirement of transcription factors
      key for early ILC development.

PMID- 29183989
TI  - Left or right? Directions to stem cell engraftment.
AB  - In this issue of JEM, Wu et al. (https://doi.org/10.1084/jem.20171341) use
      genetic barcoding of macaque hematopoietic stem cells to demonstrate that, after
      transplantation, HSCs are very asymmetrically distributed and uncover a thymus
      independent pathway for mature T cell production in the bone marrow.

PMID- 29183990
TI  - Correction: Prostate-specific membrane antigen cleavage of vitamin B9 stimulates
      oncogenic signaling through metabotropic glutamate receptors.

PMID- 29183991
TI  - Correction: Cingulo-insular structural alterations associated with psychogenic
      symptoms, childhood abuse and PTSD in functional neurological disorders.

PMID- 29183992
TI  - Structural basis for the recognition of kinesin family member 21A (KIF21A) by the
      ankyrin domains of KANK1 and KANK2 proteins.
AB  - A well-controlled microtubule organization is essential for intracellular
      transport, cytoskeleton maintenance, and cell development. KN motif and ankyrin
      repeat domain-containing protein 1 (KANK1), a member of KANK family, recruits
      kinesin family member 21A (KIF21A) to the cell cortex to control microtubule
      growth via its C-terminal ankyrin domain. However, how the KANK1 ankyrin domain
      recognizes KIF21A and whether other KANK proteins can also bind KIF21A remain
      unknown. Here, using a combination of structural, site-directed mutagenesis, and
      biochemical studies, we found that a stretch of ~22 amino acids in KIF21A is
      sufficient for binding to KANK1 and its close homolog KANK2. We further solved
      the complex structure of the KIF21A peptide with either the KANK1 ankyrin domain
      or the KANK2 ankyrin domain. In each complex, KIF21A is recognized by two
      distinct pockets of the ankyrin domain and adopts helical conformations upon
      binding to the ankyrin domain. The elucidated KANK structures may advance our
      understanding of the role of KANK1 as a scaffolding molecule in controlling
      microtubule growth at the cell periphery.

PMID- 29183993
TI  - Failed mitochondrial import and impaired proteostasis trigger SUMOylation of
      mitochondrial proteins.
AB  - Modification by the ubiquitin-like protein SUMO affects hundreds of cellular
      substrate proteins and regulates a wide variety of physiological processes. While
      the SUMO system appears to predominantly target nuclear proteins and, to a lesser
      extent, cytosolic proteins, hardly anything is known about the SUMOylation of
      proteins targeted to membrane-enclosed organelles. Here, we identify a large set
      of structurally and functionally unrelated mitochondrial proteins as substrates
      of the SUMO pathway in yeast. We show that SUMO modification of mitochondrial
      proteins does not rely on mitochondrial targeting and, in fact, is strongly
      enhanced upon import failure, consistent with the modification occurring in the
      cytosol. Moreover, SUMOylated forms of mitochondrial proteins particularly
      accumulate in HSP70- and proteasome-deficient cells, suggesting that SUMOylation
      participates in cellular protein quality control. We therefore propose that SUMO
      serves as a mark for nonfunctional mitochondrial proteins, which only
      sporadically arise in unstressed cells but strongly accumulate upon defective
      mitochondrial import and impaired proteostasis. Overall, our findings provide
      support for a role of SUMO in the cytosolic response to aberrant proteins.

PMID- 29183994
TI  - Translation efficiency is maintained at elevated temperature in Escherichia coli.
AB  - Cellular protein levels are dictated by the balance between gene transcription,
      mRNA translation, and protein degradation, among other factors. Translation
      requires the interplay of several RNA hybridization processes, which are expected
      to be temperature-sensitive. We used ribosome profiling to monitor translation in
      Escherichia coli at 30  degrees C and to investigate how this changes after 10-20
      min of heat shock at 42  degrees C. Translation efficiencies are robustly
      maintained after thermal heat shock and after mimicking the heat-shock response
      transcriptional program at 30  degrees C by overexpressing the heat shock sigma
      factor encoded by the rpoH gene. We compared translation efficiency, the ratio of
      ribosome footprint reads to mRNA reads for each gene, to parameters derived from
      gene sequences. Genes with stable mRNA structures, non-optimal codon use, and
      those whose gene product is cotranslationally translocated into the inner
      membrane are generally less highly translated than other genes. Comparison with
      other published datasets suggests a role for translational elongation in coupling
      mRNA structures to translation initiation. Genome-wide calculations of the
      temperature dependence of mRNA structure predict that relatively few mRNAs show a
      melting transition between 30 and 42  degrees C, consistent with the observed
      lack of changes in translation efficiency. We developed a linear model with six
      parameters that can predict 38% of the variation in translation efficiency
      between genes, which may be useful in interpreting transcriptome data.

PMID- 29183995
TI  - Deubiquitylase USP9X suppresses tumorigenesis by stabilizing large tumor
      suppressor kinase 2 (LATS2) in the Hippo pathway.
AB  - The Hippo pathway plays important roles in controlling organ size and in
      suppressing tumorigenesis through large tumor suppressor kinase 1/2 (LATS1/2)
      mediated phosphorylation of YAP/TAZ transcription co-activators. The kinase
      activity of LATS1/2 is regulated by phosphorylation in response to extracellular
      signals. Moreover, LATS2 protein levels are repressed by the ubiquitin-proteasome
      system in conditions such as hypoxia. However, the mechanism that removes the
      ubiquitin modification from LATS2 and thereby stabilizes the protein is not well
      understood. Here, using tandem affinity purification (TAP), we found that
      anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase complex, and
      USP9X, a deubiquitylase, specifically interact with LATS2. We also found that
      although APC1 co-localizes with LATS2 to intracellular vesicle structures, it
      does not regulate LATS2 protein levels and activity. In contrast, USP9X ablation
      drastically diminished LATS2 protein levels. We further demonstrated that USP9X
      deubiquitinates LATS2 and thus prevents LATS2 degradation by the proteasome.
      Furthermore, in pancreatic cancer cells, USP9X loss activated YAP and enhanced
      the oncogenic potential of the cells. In addition, the tumorigenesis induced by
      the USP9X ablation depended not only on LATS2 repression, but also on YAP/TAZ
      activity. We conclude that USP9X is a deubiquitylase of the Hippo pathway kinase
      LATS2 and that the Hippo pathway functions as a downstream signaling cascade that
      mediates USP9X's tumor-suppressive activity.

PMID- 29183996
TI  - Structural characterization of the bacterial proteasome homolog BPH reveals a
      tetradecameric double-ring complex with unique inner cavity properties.
AB  - Eukaryotic and archaeal proteasomes are paradigms for self-compartmentalizing
      proteases. To a large extent, their function requires interplay with hexameric
      ATPases associated with diverse cellular activities (AAA+) that act as substrate
      unfoldases. Bacteria have various types of self-compartmentalizing proteases; in
      addition to the proteasome itself, these include the proteasome homolog HslV,
      which functions together with the AAA+ HslU; the ClpP protease with its partner
      AAA+ ClpX; and Anbu, a recently characterized ancestral proteasome variant.
      Previous bioinformatic analysis has revealed a novel bacterial member of the
      proteasome family Betaproteobacteria proteasome homolog (BPH). Using cluster
      analysis, we here affirmed that BPH evolutionarily descends from HslV. Crystal
      structures of the Thiobacillus denitrificans and Cupriavidus metallidurans BPHs
      disclosed a homo-oligomeric double-ring architecture in which the active sites
      face the interior of the cylinder. Using small-angle X-ray scattering (SAXS) and
      electron microscopy averaging, we found that BPH forms tetradecamers in solution,
      unlike the dodecamers seen in HslV. Although the highly acidic inner surface of
      BPH was in striking contrast to the cavity characteristics of the proteasome and
      HslV, a classical proteasomal reaction mechanism could be inferred from the
      covalent binding of the proteasome-specific inhibitor epoxomicin to BPH. A ligand
      bound structure implied that the elongated BPH inner pore loop may be involved in
      substrate recognition. The apparent lack of a partner unfoldase and other unique
      features, such as Ser replacing Thr as the catalytic residue in certain BPH
      subfamilies, suggest a proteolytic function for BPH distinct from those of known
      bacterial self-compartmentalizing proteases.

PMID- 29183997
TI  - Hyaluronan content governs tissue stiffness in pancreatic islet inflammation.
AB  - We have identified a novel role for hyaluronan (HA), an extracellular matrix
      polymer, in governing the mechanical properties of inflamed tissues. We recently
      reported that insulitis in type 1 diabetes of mice and humans is preceded by
      intraislet accumulation of HA, a highly hygroscopic polymer. Using the double
      transgenic DO11.10 * RIPmOVA (DORmO) mouse model of type 1 diabetes, we asked
      whether autoimmune insulitis was associated with changes in the stiffness of
      islets. To measure islet stiffness, we used atomic force microscopy (AFM) and
      developed a novel "bed of nails"-like approach that uses quartz glass nanopillars
      to anchor islets, solving a long-standing problem of keeping tissue-scale objects
      immobilized while performing AFM. We measured stiffness via AFM nanoindentation
      with a spherical indenter and found that insulitis made islets mechanically soft
      compared with controls. Conversely, treatment with 4-methylumbelliferone, a small
      molecule inhibitor of HA synthesis, reduced HA accumulation, diminished swelling,
      and restored basal tissue stiffness. These results indicate that HA content
      governs the mechanical properties of islets. In hydrogels with variable HA
      content, we confirmed that increased HA leads to mechanically softer hydrogels,
      consistent with our model. In light of recent reports that the insulin production
      of islets is mechanosensitive, these findings open up an exciting new avenue of
      research into the fundamental mechanisms by which inflammation impacts local
      cellular responses.

PMID- 29183998
TI  - Chondroitin sulfate-mediated N-cadherin/beta-catenin signaling is associated with
      basal-like breast cancer cell invasion.
AB  - Tumor metastasis involves cancer cell invasion across basement membranes and
      interstitial tissues. The initial invasion step consists of adherence of the
      tumor cell to the extracellular matrix (ECM), and this binding transduces a
      variety of signals from the ECM to the tumor cell. Accordingly, it is critical to
      establish the mechanisms by which extracellular cues influence the intracellular
      activities that regulate tumor cell invasion. Here, we found that invasion of the
      basal-like breast cancer cell line BT-549 is enhanced by the ECM component
      chondroitin sulfates (CSs). CSs interacted with and induced proteolytic cleavage
      of N-cadherin in the BT-549 cells, yielding a C-terminal intracellular N-cadherin
      fragment that formed a complex with beta-catenin. Of note, the cleavage of N
      cadherin increased cytoplasmic and nuclear beta-catenin levels; induced the
      matrix metalloproteinase 9 (MMP9) gene, a target of beta-catenin nuclear
      signaling; and augmented the invasion potential of the cells. We also found that
      CS-induced N-cadherin proteolysis requires caveolae-mediated endocytosis. An
      inhibitor of that process, nystatin, blocked both the endocytosis and proteolytic
      cleavage of N-cadherin induced by CS and also suppressed BT-549 cell invasion.
      Knock-out of chondroitin 4-O-sulfotransferase-1 (C4ST-1), a key CS biosynthetic
      enzyme, suppressed activation of the N-cadherin/beta-catenin pathway through N
      cadherin endocytosis and significantly decreased BT-549 cell invasion. These
      results suggest that CSs produced by C4ST-1 might be useful therapeutic targets
      in the management of basal-like breast cancers.

PMID- 29183999
TI  - Autopolysialylation of polysialyltransferases is required for polysialylation and
      polysialic acid chain elongation on select glycoprotein substrates.
AB  - Polysialic acid (polySia) is a large glycan polymer that is added to some
      glycoproteins by two polysialyltransferases (polySTs), ST8Sia-II and ST8Sia-IV.
      As polySia modulates cell adhesion and signaling, immune cell function, and tumor
      metastasis, it is of interest to determine how the polySTs recognize their select
      substrates. We have recently identified residues within the ST8Sia-IV polybasic
      region (PBR) that are required for neural cell adhesion molecule (NCAM)
      recognition and subsequent polysialylation. Here, we compared the PBR sequence
      requirements for NCAM, neuropilin-2 (NRP-2), and synaptic cell adhesion molecule
      1 (SynCAM 1) for polysialylation by their respective polySTs. We found that the
      polySTs use unique but overlapping sets of PBR residues for substrate
      recognition, that the NCAM-recognizing PBR sites in ST8Sia-II and ST8Sia-IV
      include homologous residues, but that the ST8Sia-II site is larger, and that
      fewer PBR residues are involved in NRP-2 and SynCAM 1 recognition than in NCAM
      recognition. Noting that the two sites for ST8Sia-IV autopolysialylation flank
      the PBR, we evaluated the role of PBR residues in autopolysialylation and found
      that the requirements for polyST autopolysialylation and substrate
      polysialylation overlap. These data together with the evaluation of the polyST
      autopolysialylation mechanism enabled us to further identify PBR residues
      potentially playing dual roles in substrate recognition and in polySia chain
      polymerization. Finally, we found that ST8Sia-IV autopolysialylation is required
      for NRP-2 polysialylation and that ST8Sia-II autopolysialylation promotes the
      polymerization of longer polySia chains on SynCAM 1, suggesting a critical role
      for polyST autopolysialylation in substrate selection and polySia chain
      elongation.

PMID- 29184000
TI  - A subclass of serum anti-ZnT8 antibodies directed to the surface of live
      pancreatic beta-cells.
AB  - The islet-specific zinc transporter ZnT8 is a major self-antigen found in insulin
      granules of pancreatic beta-cells. Frequent insulin secretion exposes ZnT8 to the
      cell surface, but the humoral antigenicity of the surface-displayed ZnT8 remains
      unknown. Here we show that a membrane-embedded human ZnT8 antigen triggered a
      vigorous immune response in ZnT8 knock-out mice. Approximately 50% of serum
      immunoreactivities toward ZnT8 were mapped to its transmembrane domain that is
      accessible to extracellular ZnT8 antibody (ZnT8A). ZnT8A binding was detected on
      live rat insulinoma INS-1E cells, and the binding specificity was validated by a
      CRISPR/Cas9 mediated ZnT8 knock-out. Applying established ZnT8A assays to
      purified serum antibodies from patients with type 1 diabetes, we detected human
      ZnT8A bound to live INS-1E cells, whereas a ZnT8 knock-out specifically reduced
      the surface binding. Our results demonstrate that ZnT8 is a cell surface self
      antigen, raising the possibility of a direct involvement in antibody-mediated
      beta-cell dysfunction and cytotoxicity.

PMID- 29184001
TI  - WITHDRAWN: PACE4 Proteolytically Processes LOXL2 with little impact on its
      catalytic activity.
AB  - This article has been withdrawn by the authors. Figs 1C, 2A, and 2E contained
      some inadvertently mislabeled data. The authors state that the mislabeling does
      not affect the conclusions of the article.

PMID- 29184002
TI  - A guanine nucleotide exchange factor (GEF) limits Rab GTPase-driven membrane
      fusion.
AB  - The identity of organelles in the endomembrane system of any eukaryotic cell
      critically depends on the correctly localized Rab GTPase, which binds effectors
      and thus promotes membrane remodeling or fusion. However, it is still unresolved
      which factors are required and therefore define the localization of the correct
      fusion machinery. Using SNARE-decorated proteoliposomes that cannot fuse on their
      own, we now demonstrate that full fusion activity can be achieved by just four
      soluble factors: a soluble SNARE (Vam7), a guanine nucleotide exchange factor
      (GEF, Mon1-Ccz1), a Rab-GDP dissociation inhibitor (GDI) complex (prenylated Ypt7
      GDI), and a Rab effector complex (HOPS). Our findings reveal that the GEF Mon1
      Ccz1 is necessary and sufficient for stabilizing prenylated Ypt7 on membranes.
      HOPS binding to Ypt7-GTP then drives SNARE-mediated fusion, which is fully GTP
      dependent. We conclude that an entire fusion cascade can be controlled by a GEF.

PMID- 29184003
TI  - IL-10 promoter transactivation by the viral K-RTA protein involves the host-cell
      transcription factors, specificity proteins 1 and 3.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) causes
      a persistent infection, presenting latent and lytic replication phases during its
      life cycle. KSHV-related diseases are associated with deregulated expression of
      inflammatory cytokines, including IL-6 and IL-10, but the mechanisms underlying
      this dysregulation are unclear. Herein, we report a molecular mechanism for KSHV
      induced IL-10 gene expression. KSHV replication and transcription activator (K
      RTA) is a molecular switch for the initiation of expression of viral lytic genes,
      and we describe, for the first time, that K-RTA significantly activates the
      promoter of the human IL-10 gene. Of note, mutations involving a basic region of
      K-RTA reduced the association of K-RTA with the IL-10 promoter. Moreover, the
      host-cell transcription factors, specificity proteins (SP) 1 and 3, play a
      pivotal cooperative role in K-RTA-mediated transactivation of the IL-10 promoter.
      K-RTA can interact with SP1 and SP3 directly in vitro, and electrophoresis
      mobility shift assays (EMSAs) revealed co-operative interaction involving K-RTA,
      SP1, and SP3 in binding to the IL-10 promoter. As DNase I footprinting assays
      indicated that K-RTA did not affect SP3 binding to the IL-10 promoter, SP3 can
      function to recruit K-RTA to the IL-10 promoter. These findings indicate that K
      RTA can directly contribute to IL-10 up-regulation via a functional interplay
      with the cellular transcription factors SP1 and SP3.

PMID- 29184005
TI  - An infant with congenital rubella syndrome in developing India.
AB  - Congenital rubella syndrome (CRS), caused by rubella virus infection during
      pregnancy, remains a public health concern in developing countries. Three to five
      per cent of all suspected CRS cases in India have been proven to be a rubella
      infection. Only about 45%-60% of pregnant women and infants in India receive the
      rubella vaccination. We present a case of a preterm female infant who tested
      positive for the rubella virus. The baby was born with low birth weight and, on
      examination, showed pallor and hepatosplenomegaly. She was detected to have an
      ostium secundum atrial septal defect (ASD) and a large patent ductus arteriosus
      (PDA) on echocardiography. On ophthalmic examination, she was diagnosed with
      bilateral cataract. She was treated with diuretics, and she underwent surgical
      correction for PDA. With this case we intend to present the literature, clinical
      manifestations and management of CRS. We will also focus on prevention,
      vaccination and disease burden in India.?.

PMID- 29184004
TI  - A global view of structure-function relationships in the tautomerase superfamily.
AB  - The tautomerase superfamily (TSF) consists of more than 11,000 nonredundant
      sequences present throughout the biosphere. Characterized members have attracted
      much attention because of the unusual and key catalytic role of an N-terminal
      proline. These few characterized members catalyze a diverse range of chemical
      reactions, but the full scale of their chemical capabilities and biological
      functions remains unknown. To gain new insight into TSF structure-function
      relationships, we performed a global analysis of similarities across the entire
      superfamily and computed a sequence similarity network to guide classification
      into distinct subgroups. Our results indicate that TSF members are found in all
      domains of life, with most being present in bacteria. The eukaryotic members of
      the cis-3-chloroacrylic acid dehalogenase subgroup are limited to fungal species,
      whereas the macrophage migration inhibitory factor subgroup has wide eukaryotic
      representation (including mammals). Unexpectedly, we found that 346 TSF sequences
      lack Pro-1, of which 85% are present in the malonate semialdehyde decarboxylase
      subgroup. The computed network also enabled the identification of similarity
      paths, namely sequences that link functionally diverse subgroups and exhibit
      transitional structural features that may help explain reaction divergence. A
      structure-guided comparison of these linker proteins identified conserved
      transitions between them, and kinetic analysis paralleled these observations.
      Phylogenetic reconstruction of the linker set was consistent with these findings.
      Our results also suggest that contemporary TSF members may have evolved from a
      short 4-oxalocrotonate tautomerase-like ancestor followed by gene duplication and
      fusion. Our new linker-guided strategy can be used to enrich the discovery of
      sequence/structure/function transitions in other enzyme superfamilies.

PMID- 29184006
TI  - Pain improvement in Camurati-Engelmann disease after anti-TNFalpha therapy.
AB  - Camurati-Engelmann disease (CED) is a rare disorder included in the group of
      craniotubular hyperostosis diseases. Corticosteroids are used for pain management
      in CED, but in refractory or corticosteroid-non-tolerant patients, pain
      management is limited. We report the case of a woman with CED diagnosed in early
      infancy whose initial complaints included persistent bone pain associated with
      progressive functional disability. She was treated with steroids but over time
      became dependent on higher doses with only mild pain relief. In her third decade,
      she was diagnosed with ulcerative colitis (UC) and was treated with mesalazine,
      azathioprine and prednisolone. Due to recurrent exacerbations of UC, treatment
      was changed to infliximab, an antitumour necrosis factor-alpha (TNFalpha).
      Remission of UC was achieved and CED-associated pain also improved with
      infliximab. This is the first report showing a possible role of anti-TNFalpha in
      pain management in CED with unsatisfactory response to steroids.

PMID- 29184007
TI  - Beware the middle-aged migraine: internal carotid artery dissection mimicking
      migraine in the emergency department.

PMID- 29184008
TI  - Bilateral breast filariasis mimicking inflammatory breast carcinoma.
AB  - Breast is an uncommon site to be affected in filariasis. However, such cases may
      be encountered in endemic areas. Here, we report a case of filariasis of breast
      in a 55-year-old woman who was clinically mistaken for inflammatory carcinoma of
      the breast. Sonomammography revealed classic signs pointing towards the diagnosis
      of filariasis of breast, which was confirmed with microscopic examination of fine
      needle aspirate. Thus, imaging played a pivotal role in correctly diagnosing and
      further altering the line of management.

PMID- 29184009
TI  - Disseminated hydatid cyst of liver and lung.
AB  - Hydatid cyst commonly affects liver followed by lung, but rarely affects both
      organs simultaneously. Here we presented a patient who presented with concurrent
      involvement of both lungs and liver. Patient presented with dyspnoea and
      generalised weakness with bilateral rounded opacities throughout the lung field
      of variable sizes. CT scan chest with contrast showed multiple rounded soft
      tissue density in both lungs and liver. Patient underwent mini thoracotomy which
      revealed multiple cystic lesions throughout lung. ELISA for anti-Echinococcus
      antibodies shows positive titres. Due to extensive involvement, patient was
      started on medical treatment albendazole. The patient showed significant
      improvement both clinically and radiographically on treatment. Thus long-term
      medical treatment helps in such cases where surgery is not possible.

PMID- 29184010
TI  - Delayed massive haemothorax 10 days following percutaneous nephrolithotomy.
AB  - A 56-year-old man presented with massive right haemothorax 10 days following
      percutaneous nephrolithotomy (PCNL) for complex, large-bulk, right renal stones.
      Antiplatelet medication started following coronary stenting 7 months ago was
      stopped 5 days prior and resumed 2 days following surgery. Stones were cleared
      through two tracts, one supracostal, with placement of ureteral stent but no
      nephrostomy. He was discharged the next day with an unremarkable chest X-ray. He
      developed cough and fever after 1 week. Three days later he presented with acute
      dyspnoea, blood pressure of 100/60 mm Hg, pulse of 120/min and haemoglobin of 9.0
      g/dL. Chest X-ray and CT scan showed a large right haemothorax. Two-litre
      haemothorax was drained by intercostal drainage with prompt recovery. Haemothorax
      is a rare complication following PCNL usually after supracostal access. Most
      occur at or immediately following surgery. Infection and early resumption of
      antiplatelet medication might have contributed to his presentation with delayed
      secondary haemorrhage from a pleural injury.

PMID- 29184011
TI  - Right heart transiting thrombi caused by endovenous sclerotherapy: the treatment
      is not consensual.

PMID- 29184012
TI  - Fatal colitis associated with active systemic lupus erythematosus complicated by
      cytomegalovirus superinfection.

PMID- 29184013
TI  - Time to ask patients about drugs for macular degeneration.

PMID- 29184014
TI  - Recipient-Biased Competition for an Intracellularly Generated Cross-Fed Nutrient
      Is Required for Coexistence of Microbial Mutualists.
AB  - Many mutualistic microbial relationships are based on nutrient cross-feeding.
      Traditionally, cross-feeding is viewed as being unidirectional, from the producer
      to the recipient. This is likely true when a producer's waste, such as a
      fermentation product, has value only for a recipient. However, in some cases the
      cross-fed nutrient holds value for both the producer and the recipient. In such
      cases, there is potential for nutrient reacquisition by producer cells in a
      population, leading to competition against recipients. Here, we investigated the
      consequences of interpartner competition for cross-fed nutrients on mutualism
      dynamics by using an anaerobic coculture pairing fermentative Escherichia coli
      and phototrophic Rhodopseudomonas palustris In this coculture, E. coli excretes
      waste organic acids that provide a carbon source for R. palustris In return, R.
      palustris cross-feeds E. coli ammonium (NH4+), a compound that both species
      value. To explore the potential for interpartner competition, we first used a
      kinetic model to simulate cocultures with varied affinities for NH4+ in each
      species. The model predicted that interpartner competition for NH4+ could
      profoundly impact population dynamics. We then experimentally tested the
      predictions by culturing mutants lacking NH4+ transporters in both NH4+
      competition assays and mutualistic cocultures. Both theoretical and experimental
      results indicated that the recipient must have a competitive advantage in
      acquiring cross-fed NH4+ to sustain the mutualism. This recipient-biased
      competitive advantage is predicted to be crucial, particularly when the
      communally valuable nutrient is generated intracellularly. Thus, the very
      metabolites that form the basis for mutualistic cross-feeding can also be subject
      to competition between mutualistic partners.IMPORTANCE Mutualistic relationships,
      particularly those based on nutrient cross-feeding, promote stability of diverse
      ecosystems and drive global biogeochemical cycles. Cross-fed nutrients within
      these systems can be either waste products valued by only one partner or
      nutrients valued by both partners. Here, we explored how interpartner competition
      for a communally valuable cross-fed nutrient impacts mutualism dynamics. We
      discovered that mutualism stability necessitates that the recipient have a
      competitive advantage against the producer in obtaining the cross-fed nutrient,
      provided that the nutrient is generated intracellularly. We propose that the
      requirement for recipient-biased competition is a general rule for mutualistic
      coexistence based on the transfer of intracellularly generated, communally
      valuable resources.

PMID- 29184015
TI  - Molecular Basis of Bacterial Longevity.
AB  - It is well known that many bacteria can survive in a growth-arrested state for
      long periods of time, on the order of months or even years, without forming
      dormant structures like spores or cysts. How is such longevity possible? What is
      the molecular basis of such longevity? Here we used the Gram-negative
      phototrophic alphaproteobacterium Rhodopseudomonas palustris to identify
      molecular determinants of bacterial longevity. R. palustris maintained viability
      for over a month after growth arrest due to nutrient depletion when it was
      provided with light as a source of energy. In transposon sequencing (Tn-seq)
      experiments, we identified 117 genes that were required for long-term viability
      of nongrowing R. palustris cells. Genes in this longevity gene set are annotated
      to play roles in a number of cellular processes, including DNA repair, tRNA
      modification, and the fidelity of protein synthesis. These genes are critically
      important only when cells are not growing. Three genes annotated to affect
      translation or posttranslational modifications were validated as bona fide
      longevity genes by mutagenesis and complementation experiments. These genes and
      others in the longevity gene set are broadly conserved in bacteria. This raises
      the possibility that it will be possible to define a core set of longevity genes
      common to many bacterial species.IMPORTANCE Bacteria in nature and during
      infections often exist in a nongrowing quiescent state. However, it has been
      difficult to define experimentally the molecular characteristics of this crucial
      element of the bacterial life cycle because bacteria that are not growing tend to
      die under laboratory conditions. Here we present and validate the phototrophic
      bacterium Rhodopseudomonas palustris as a model system for identification of
      genes required for the longevity of nongrowing bacteria. Growth-arrested R.
      palustris maintained almost full viability for weeks using light as an energy
      source. Such cells were subjected to large-scale mutagenesis to identify genes
      required for this striking longevity trait. The results define conserved
      determinants of survival under nongrowing conditions and create a foundation for
      more extensive studies to elucidate general molecular mechanisms of bacterial
      longevity.

PMID- 29184016
TI  - Subversion of Metabolic Wasting as the Mechanism for folM-Linked Sulfamethoxazole
      Resistance.

PMID- 29184017
TI  - Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles Protects
      Mice against Cryptococcosis in a Manner Dependent upon Mouse Strain and
      Cryptococcal Species.
AB  - Development of a vaccine to protect against cryptococcosis is a priority given
      the enormous global burden of disease in at-risk individuals. Using glucan
      particles (GPs) as a delivery system, we previously demonstrated that mice
      vaccinated with crude Cryptococcus-derived alkaline extracts were protected
      against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii The
      goal of the present study was to identify protective protein antigens that could
      be used in a subunit vaccine. Using biased and unbiased approaches, six candidate
      antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly
      expressed in Escherichia coli, purified, and loaded into GPs. Three mouse strains
      (C57BL/6, BALB/c, and DR4) were then vaccinated with the antigen-laden GPs,
      following which they received a pulmonary challenge with virulent C. neoformans
      and C. gattii strains. Four candidate vaccines (GP-Cda1, GP-Cda2, GP-Cda3, and GP
      Sod1) afforded a significant survival advantage in at least one mouse model; some
      vaccine combinations provided added protection over that seen with either antigen
      alone. Vaccine-mediated protection against C. neoformans did not necessarily
      predict protection against C. gattii Vaccinated mice developed pulmonary
      inflammatory responses that effectively contained the infection; many surviving
      mice developed sterilizing immunity. Predicted T helper cell epitopes differed
      between mouse strains and in the degree to which they matched epitopes predicted
      in humans. Thus, we have discovered cryptococcal proteins that make promising
      candidate vaccine antigens. Protection varied depending on the mouse strain and
      cryptococcal species, suggesting that a successful human subunit vaccine will
      need to contain multiple antigens, including ones that are species
      specific.IMPORTANCE The encapsulated fungi Cryptococcus neoformans and
      Cryptococcus gattii are responsible for nearly 200,000 deaths annually, mostly in
      immunocompromised individuals. An effective vaccine could substantially reduce
      the burden of cryptococcosis. However, a major gap in cryptococcal vaccine
      development has been the discovery of protective antigens to use in vaccines.
      Here, six cryptococcal proteins with potential as vaccine antigens were expressed
      recombinantly and purified. Mice were then vaccinated with glucan particle
      preparations containing each antigen. Of the six candidate vaccines, four
      protected mice from a lethal cryptococcal challenge. However, the degree of
      protection varied as a function of mouse strain and cryptococcal species. These
      preclinical studies identify cryptococcal proteins that could serve as candidate
      vaccine antigens and provide a proof of principle regarding the feasibility of
      protein antigen-based vaccines to protect against cryptococcosis.

PMID- 29184019
TI  - Gut Symbiont Bacteroides fragilis Secretes a Eukaryotic-Like Ubiquitin Protein
      That Mediates Intraspecies Antagonism.
AB  - Human gut Bacteroides species produce different types of toxins that antagonize
      closely related members of the gut microbiota. Some are toxic effectors delivered
      by type VI secretion systems, and others are non-contact-dependent secreted
      antimicrobial proteins. Many strains of Bacteroides fragilis secrete
      antimicrobial molecules, but only one of these toxins has been described to date
      (Bacteroidales secreted antimicrobial protein 1 [BSAP-1]). In this study, we
      describe a novel secreted protein produced by B. fragilis strain 638R that
      mediated intraspecies antagonism. Using transposon mutagenesis and deletion
      mutation, we identified a gene encoding a eukaryotic-like ubiquitin protein
      (BfUbb) necessary for toxin activity against a subset of B. fragilis strains. The
      addition of ubb into a heterologous background strain conferred toxic activity on
      that strain. We found this gene to be one of the most highly expressed in the B.
      fragilis genome. The mature protein is 84% similar to human ubiquitin but has an
      N-terminal signal peptidase I (SpI) signal sequence and is secreted
      extracellularly. We found that the mature 76-amino-acid synthetic protein has
      very potent activity, confirming that BfUbb mediates the activity. Analyses of
      human gut metagenomic data sets revealed that ubb is present in 12% of the
      metagenomes that have evidence of B. fragilis As 638R produces both BSAP-1 and
      BfUbb, we performed a comprehensive analysis of the toxin activity of BSAP-1 and
      BfUbb against a set of 40 B. fragilis strains, revealing that 75% of B. fragilis
      strains are targeted by one or the other of these two secreted proteins of strain
      638R.IMPORTANCE We are just beginning to understand some of the important
      interactions that occur between microbes of the human gut microbiota that dictate
      the composition and abundance of its constituent members. The ability of one
      member to produce molecules that directly kill a coresident member has been shown
      among minor gut species and is just starting to be studied in the abundant
      Bacteroides species. Here, we show that some strains of Bacteroides fragilis have
      acquired a gene encoding a secreted eukaryotic-like ubiquitin protein with potent
      inhibitory activity against other B. fragilis stains. This is the first
      bacterially encoded ubiquitin-like molecule shown to function like a bacterial
      toxin. This molecule is an example of a gut symbiont acquiring and adapting a
      eukaryotic molecule likely to increase its competitiveness in the mammalian gut.
      Understanding antagonistic factors produced by abundant gut symbionts is an
      important prerequisite to properly engineer strains to colonize the gut for
      health benefits.

PMID- 29184018
TI  - Ancient Regulatory Role of Lysine Acetylation in Central Metabolism.
AB  - Lysine acetylation is a common protein post-translational modification in
      bacteria and eukaryotes. Unlike phosphorylation, whose functional role in
      signaling has been established, it is unclear what regulatory mechanism
      acetylation plays and whether it is conserved across evolution. By performing a
      proteomic analysis of 48 phylogenetically distant bacteria, we discovered
      conserved acetylation sites on catalytically essential lysine residues that are
      invariant throughout evolution. Lysine acetylation removes the residue's charge
      and changes the shape of the pocket required for substrate or cofactor binding.
      Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are
      acetylated at these critical sites. Our data suggest that acetylation may play a
      direct role in metabolic regulation by switching off enzyme activity. We propose
      that protein acetylation is an ancient and widespread mechanism of protein
      activity regulation.IMPORTANCE Post-translational modifications can regulate the
      activity and localization of proteins inside the cell. Similar to
      phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes
      and modifies hundreds to thousands of proteins in cells. However, how lysine
      acetylation regulates protein function and whether such a mechanism is
      evolutionarily conserved is still poorly understood. Here, we investigated
      evolutionary and functional aspects of lysine acetylation by searching for
      acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically
      distant bacteria. We found that lysine acetylation occurs in evolutionarily
      conserved lysine residues in catalytic sites of enzymes involved in central
      carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our
      observations suggest that lysine acetylation is an evolutionarily conserved
      mechanism of controlling central metabolic activity by directly blocking enzyme
      active sites.

PMID- 29184020
TI  - Bacteriophage Distributions and Temporal Variability in the Ocean's Interior.
AB  - Bacteriophages are numerically the most abundant DNA-containing entities in the
      oligotrophic ocean, yet how specific phage populations vary over time and space
      remains to be fully explored. Here, we conducted a metagenomic time-series survey
      of double-stranded DNA phages throughout the water column in the North Pacific
      Subtropical Gyre, encompassing 1.5 years from depths of 25 to 1,000 m. Viral gene
      sequences were identified in assembled metagenomic samples, yielding an estimated
      172,385 different viral gene families. Viral marker gene distributions suggested
      that lysogeny was more prevalent at mesopelagic depths than in surface waters,
      consistent with prior prophage induction studies using mitomycin C. A total of
      129 ALOHA viral genomes and genome fragments from 20 to 108 kbp were selected for
      further study, which represented the most abundant phages in the water column.
      Phage genotypes displayed discrete population structures. Most phages persisted
      throughout the time-series and displayed a strong depth structure that mirrored
      the stratified depth distributions of co-occurring bacterial taxa in the water
      column. Mesopelagic phages were distinct from surface water phages with respect
      to diversity, gene content, putative life histories, and temporal persistence,
      reflecting depth-dependent differences in host genomic architectures and phage
      reproductive strategies. The spatiotemporal distributions of the most abundant
      open-ocean bacteriophages that we report here provide new insight into viral
      temporal persistence, life history, and virus-host-environment interactions
      throughout the open-ocean water column.IMPORTANCE The North Pacific Subtropical
      Gyre represents one of the largest biomes on the planet, where microbial
      communities are central mediators of ecosystem dynamics and global biogeochemical
      cycles. Critical members of these communities are the viruses of marine bacteria,
      which can alter microbial metabolism and significantly influence their survival
      and productivity. To better understand these viral assemblages, we conducted
      genomic analyses of planktonic viruses over a seasonal cycle to ocean depths of
      1,000 m. We identified 172,385 different viral gene families and 129 unique virus
      genotypes in this open-ocean setting. The spatiotemporal distributions of the
      most abundant open-ocean viruses that we report here provide new insights into
      viral temporal variability, life history, and virus-host-environment interactions
      throughout the water column.

PMID- 29184021
TI  - Forward Genetics Approach Reveals Host Genotype-Dependent Importance of Accessory
      Chromosomes in the Fungal Wheat Pathogen Zymoseptoria tritici.
AB  - The fungal wheat pathogen Zymoseptoria tritici possesses a large complement of
      accessory chromosomes showing presence/absence polymorphism among isolates. These
      chromosomes encode hundreds of genes; however, their functional role and why the
      chromosomes have been maintained over long evolutionary times are so far not
      known. In this study, we addressed the functional relevance of eight accessory
      chromosomes in reference isolate IPO323. We induced chromosome losses by
      inhibiting the beta-tubulin assembly during mitosis using carbendazim and
      generated several independent isogenic strains, each lacking one of the accessory
      chromosomes. We confirmed chromosome losses by electrophoretic karyotyping and
      whole-genome sequencing. To assess the importance of the individual chromosomes
      during host infection, we performed in planta assays comparing disease
      development results in wild-type and chromosome mutant strains. Loss of the
      accessory chromosomes 14, 16, 18, 19, and 21 resulted in increased virulence on
      wheat cultivar Runal but not on cultivars Obelisk, Titlis, and Riband. Moreover,
      some accessory chromosomes affected the switch from biotrophy to necrotrophy as
      strains lacking accessory chromosomes 14, 18, 19, and 21 showed a significantly
      earlier onset of necrosis than the wild type on the Runal cultivar. In general,
      we observed that the timing of the lifestyle switch affects the fitness of Z.
      tritici Taking the results together, this study was the first to use a forward
      genetics approach to demonstrate a cultivar-dependent functional relevance of the
      accessory chromosomes of Z. tritici during host infection.IMPORTANCEZymoseptoria
      tritici is a prominent fungal pathogen of wheat of worldwide distribution. This
      fungus shows a remarkable genome organization, with a large number of chromosomes
      that are present in only some isolates and therefore considered to be "accessory"
      chromosomes. To date, the function of these accessory chromosomes in Z. tritici
      has been unknown, although their maintenance in the species over evolutionary
      times suggests a functional relevance. Here we deleted whole accessory
      chromosomes to test the effect of these chromosomes on host specificity and
      virulence of the fungus. We show for the first time that some accessory
      chromosomes of Z. tritici affect the fitness of the fungus during host infection
      in a cultivar-dependent manner. These results show that the accessory chromosomes
      encode host-specific virulence determinants having a negative effect on fitness.
      Understanding the population dynamic of the accessory chromosomes and the
      molecular interaction of pathogen and plant traits is crucial to improve wheat
      breeding strategies.

PMID- 29184022
TI  - Interventions on Metabolism: Making Antibiotic-Susceptible Bacteria.
AB  - Antibiotics act on bacterial metabolism, and antibiotic resistance involves
      changes in this metabolism. Interventions on metabolism with drugs might
      therefore modify drug susceptibility and drug resistance. In their recent
      article, Martin Vestergaard et al. (mBio 8:e01114-17, 2017,
      https://doi.org/10.1128/mBio.01114-17) illustrate the possibility of converting
      intrinsically resistant bacteria into susceptible ones. They reported that
      inhibition of a central metabolic enzyme, ATP synthase, allows otherwise
      ineffective polymyxin antibiotics to act on Staphylococcus aureus The study of
      the intrinsic resistome of bacterial pathogens has shown that several metabolic
      genes, including multigene transcriptional regulators, contribute to antibiotic
      resistance. In some cases, these genes only marginally increase antibiotic
      resistance, but reduced levels of susceptibility might be critical in the
      evolution or resistance under low antibiotic concentrations or in the clinical
      response of highly resistant bacteria. Drug interventions on bacterial metabolism
      might constitute a critical adjuvant therapy in combination with antibiotics to
      ensure susceptibility of pathogens with intrinsic or acquired antimicrobial
      resistance.

PMID- 29184023
TI  - Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex
      Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T
      Lymphocyte Escape of HIV-1 Gag Epitopes.
AB  - Certain "protective" major histocompatibility complex class I (MHC-I) alleles,
      such as B*57 and B*27, are associated with long-term control of HIV-1 in vivo
      mediated by the CD8+ cytotoxic-T-lymphocyte (CTL) response. However, the
      mechanism of such superior protection is not fully understood. Here we combined
      high-throughput fitness profiling of mutations in HIV-1 Gag, in silico prediction
      of MHC-peptide binding affinity, and analysis of intraperson virus evolution to
      systematically compare differences with respect to CTL escape mutations between
      epitopes targeted by protective MHC-I alleles and those targeted by nonprotective
      MHC-I alleles. We observed that the effects of mutations on both viral
      replication and MHC-I binding affinity are among the determinants of CTL escape.
      Mutations in Gag epitopes presented by protective MHC-I alleles are associated
      with significantly higher fitness cost and lower reductions in binding affinity
      with respect to MHC-I. A linear regression model accounting for the effect of
      mutations on both viral replicative capacity and MHC-I binding can explain the
      protective efficacy of MHC-I alleles. Finally, we found a consistent pattern in
      the evolution of Gag epitopes in long-term nonprogressors versus progressors.
      Overall, our results suggest that certain protective MHC-I alleles allow superior
      control of HIV-1 by targeting epitopes where mutations typically incur high
      fitness costs and small reductions in MHC-I binding affinity.IMPORTANCE
      Understanding the mechanism of viral control achieved in long-term nonprogressors
      with protective HLA alleles provides insights for developing functional cure of
      HIV infection. Through the characterization of CTL escape mutations in infected
      persons, previous researchers hypothesized that protective alleles target
      epitopes where escape mutations significantly reduce viral replicative capacity.
      However, these studies were usually limited to a few mutations observed in vivo
      Here we utilized our recently developed high-throughput fitness profiling method
      to quantitatively measure the fitness of mutations across the entirety of HIV-1
      Gag. The data enabled us to integrate the results with in silico prediction of
      MHC-peptide binding affinity and analysis of intraperson virus evolution to
      systematically determine the differences in CTL escape mutations between epitopes
      targeted by protective HLA alleles and those targeted by nonprotective HLA
      alleles. We observed that the effects of Gag epitope mutations on HIV replicative
      fitness and MHC-I binding affinity are among the major determinants of CTL
      escape.

PMID- 29184024
TI  - Identification of Fitness Determinants during Energy-Limited Growth Arrest in
      Pseudomonas aeruginosa.
AB  - Microbial growth arrest can be triggered by diverse factors, one of which is
      energy limitation due to scarcity of electron donors or acceptors. Genes that
      govern fitness during energy-limited growth arrest and the extent to which they
      overlap between different types of energy limitation are poorly defined. In this
      study, we exploited the fact that Pseudomonas aeruginosa can remain viable over
      several weeks when limited for organic carbon (pyruvate) as an electron donor or
      oxygen as an electron acceptor. ATP values were reduced under both types of
      limitation, yet more severely in the absence of oxygen. Using transposon
      insertion sequencing (Tn-seq), we identified fitness determinants in these two
      energy-limited states. Multiple genes encoding general functions like
      transcriptional regulation and energy generation were required for fitness during
      carbon or oxygen limitation, yet many specific genes, and thus specific
      activities, differed in their relevance between these states. For instance, the
      global regulator RpoS was required during both types of energy limitation, while
      other global regulators such as DksA and LasR were required only during carbon or
      oxygen limitation, respectively. Similarly, certain ribosomal and tRNA
      modifications were specifically required during oxygen limitation. We validated
      fitness defects during energy limitation using independently generated mutants of
      genes detected in our screen. Mutants in distinct functional categories exhibited
      different fitness dynamics: regulatory genes generally manifested a phenotype
      early, whereas genes involved in cell wall metabolism were required later.
      Together, these results provide a new window into how P. aeruginosa survives
      growth arrest.IMPORTANCE Growth-arrested bacteria are ubiquitous in nature and
      disease yet understudied at the molecular level. For example, growth-arrested
      cells constitute a major subpopulation of mature biofilms, serving as an
      antibiotic-tolerant reservoir in chronic infections. Identification of the genes
      required for survival of growth arrest (encompassing entry, maintenance, and
      exit) is an important first step toward understanding the physiology of bacteria
      in this state. Using Tn-seq, we identified and validated genes required for
      fitness of Pseudomonas aeruginosa when energy limited for organic carbon or
      oxygen, which represent two common causes of growth arrest for P. aeruginosa in
      diverse habitats. This unbiased, genome-wide survey is the first to reveal
      essential activities for a pathogen experiencing different types of energy
      limitation, finding both shared and divergent activities that are relevant at
      different survival stages. Future efforts can now be directed toward
      understanding how the biomolecules responsible for these activities contribute to
      fitness under these conditions.

PMID- 29184025
TI  - Microbial Community Structure and Arsenic Biogeochemistry in Two Arsenic-Impacted
      Aquifers in Bangladesh.
AB  - Long-term exposure to trace levels of arsenic (As) in shallow groundwater used
      for drinking and irrigation puts millions of people at risk of chronic disease.
      Although microbial processes are implicated in mobilizing arsenic from aquifer
      sediments into groundwater, the precise mechanism remains ambiguous. The goal of
      this work was to target, for the first time, a comprehensive suite of state-of
      the-art molecular techniques in order to better constrain the relationship
      between indigenous microbial communities and the iron and arsenic mineral phases
      present in sediments at two well-characterized arsenic-impacted aquifers in
      Bangladesh. At both sites, arsenate [As(V)] was the major species of As present
      in sediments at depths with low aqueous As concentrations, while most sediment As
      was arsenite [As(III)] at depths with elevated aqueous As concentrations. This is
      consistent with a role for the microbial As(V) reduction in mobilizing arsenic.
      16S rRNA gene analysis indicates that the arsenic-rich sediments were colonized
      by diverse bacterial communities implicated in both dissimilatory Fe(III) and
      As(V) reduction, while the correlation analyses involved phylogenetic groups not
      normally associated with As mobilization. Findings suggest that direct As redox
      transformations are central to arsenic fate and transport and that there is a
      residual reactive pool of both As(V) and Fe(III) in deeper sediments that could
      be released by microbial respiration in response to hydrologic perturbation, such
      as increased groundwater pumping that introduces reactive organic carbon to
      depth.IMPORTANCE The consumption of arsenic in waters collected from tube wells
      threatens the lives of millions worldwide and is particularly acute in the
      floodplains and deltas of southern Asia. The cause of arsenic mobilization from
      natural sediments within these aquifers to groundwater is complex, with recent
      studies suggesting that sediment-dwelling microorganisms may be the cause. In the
      absence of oxygen at depth, specialist bacteria are thought able to use metals
      within the sediments to support their metabolism. Via these processes, arsenic
      contaminated iron minerals are transformed, resulting in the release of arsenic
      into the aquifer waters. Focusing on a field site in Bangladesh, a comprehensive,
      multidisciplinary study using state-of-the-art geological and microbiological
      techniques has helped better understand the microbes that are present naturally
      in a high-arsenic aquifer and how they may transform the chemistry of the
      sediment to potentially lethal effect.

PMID- 29184027
TI  - Vacuolar Trafficking Protein VPS38 Is Dispensable for Autophagy.
AB  - Phosphatidylinositol 3-P (PI3P) is a signaling molecule that controls a variety
      of processes in endosomal, autophagic, and vacuolar/lysosomal trafficking in
      yeasts and mammals. Vacuolar protein sorting 34 (Vps34) is a conserved PI3K
      present in multiple complexes with specific functions and regulation. In yeast,
      the PI3K complex II consists of Vps34p, Vps15p, Vps30p/Atg6p, and Vps38p, and is
      essential for vacuolar protein sorting. Here, we describe the Arabidopsis
      (Arabidopsis thaliana) homolog of yeast Vps38p and human UV radiation resistance
      associated gene protein. Arabidopsis VPS38 interacts with VPS30/ATG6 both in
      yeast and in planta. Although the level of PI3P in Arabidopsis vps38 mutants is
      similar to that in wild type, vps38 cells contain enlarged multivesicular
      endosomes and fewer organelles enriched in PI3P than the wild type. The vps38
      mutants are defective in the trafficking of vacuolar cargo and its receptor
      VACUOLAR SORTING RECEPTOR2;1. The mutants also exhibit abnormal cytoplasmic
      distributions of endocytic cargo, such as auxin efflux carriers PINFORMED1 (PIN1)
      and PIN2. Constitutive autophagy is normal in the mutants but starvation-induced
      autophagy was slightly inhibited. We conclude that Arabidopsis VPS38 is
      dispensable for autophagy but essential for efficient targeting of biosynthetic
      and endocytic cargo to the vacuole.

PMID- 29184028
TI  - Identification of a New Host Factor Required for Antiviral RNAi and Amplification
      of Viral siRNAs.
AB  - Small interfering RNAs (siRNAs) are processed from virus-specific dsRNA to direct
      antiviral RNA interference (RNAi) in diverse eukaryotic hosts. We have recently
      performed a sensitized genetic screen in Arabidopsis (Arabidopsis thaliana) and
      identified two related phospholipid flippases required for antiviral RNAi and the
      amplification of virus-derived siRNAs by plant RNA-dependent RNA polymerase1
      (RDR1) and RDR6. Here we report the identification and cloning of ANTIVIRAL RNAI
      DEFECTIVE2 (AVI2) from the same genetic screen. AVI2 encodes a multispan
      transmembrane protein broadly conserved in plants and animals with two homologous
      human proteins known as magnesium transporters. We show that avi2 mutant plants
      display no developmental defects and develop severe disease symptoms after
      infection with a mutant Cucumber mosaic virus (CMV) defective in RNAi
      suppression. AVI2 is induced by CMV infection, particularly in veins, and is
      required for antiviral RNAi and RDR6-dependent biogenesis of viral siRNAs. AVI2
      is also necessary for Dicer-like2-mediated amplification of 22-nucleotide viral
      siRNAs induced in dcl4 mutant plants by infection, but dispensable for RDR6
      dependent biogenesis of endogenous transacting siRNAs. Further genetic studies
      illustrate that AVI2 plays a partially redundant role with AVI2H, the most
      closely related member in the AVI2 gene family, in RDR1-dependent biogenesis of
      viral siRNAs and the endogenous virus-activated siRNAs (vasi-RNAs).
      Interestingly, we discovered a specific genetic interaction of AVI2 with AVI1
      flippase that is critical for plant development. We propose that AVI1 and AVI2
      participate in the virus-induced formation of the RDR1/RDR6-specific, membrane
      bound RNA synthesis compartment, essential for the biogenesis of highly abundant
      viral siRNAs and vasi-RNAs.

PMID- 29184030
TI  - Arabidopsis ATXR2 deposits H3K36me3 at the promoters of LBD genes to facilitate
      cellular dedifferentiation.
AB  - Cellular dedifferentiation, the transition of differentiated somatic cells to
      pluripotent stem cells, ensures developmental plasticity and contributes to wound
      healing in plants. Wounding induces cells to form a mass of unorganized
      pluripotent cells called callus at the wound site. Explanted cells can also form
      callus tissues in vitro. Reversible cellular differentiation-dedifferentiation
      processes in higher eukaryotes are controlled mainly by chromatin modifications.
      We demonstrate that ARABIDOPSIS TRITHORAX-RELATED 2 (ATXR2), a histone lysine
      methyltransferase that promotes the accumulation of histone H3 proteins that are
      trimethylated on lysine 36 (H3K36me3) during callus formation, promotes early
      stages of cellular dedifferentiation through activation of LATERAL ORGAN
      BOUNDARIES DOMAIN (LBD) genes. The LBD genes of Arabidopsis thaliana are
      activated during cellular dedifferentiation to enhance the formation of callus.
      Leaf explants from Arabidopsis atxr2 mutants exhibited a reduced ability to form
      callus and a substantial reduction in LBD gene expression. ATXR2 bound to the
      promoters of LBD genes and was required for the deposition of H3K36me3 at these
      promoters. ATXR2 was recruited to LBD promoters by the transcription factors
      AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19. Leaf explants from arf7-1arf19-2 double
      mutants were defective in callus formation and showed reduced H3K36me3
      accumulation at LBD promoters. Genetic analysis provided further support that
      ARF7 and ARF19 were required for the ability of ATXR2 to promote the expression
      of LBD genes. These observations indicate that the ATXR2-ARF-LBD axis is key for
      the epigenetic regulation of callus formation in Arabidopsis.

PMID- 29184032
TI  - Opening the Orai1 gates.
AB  - How the store-operated channel Orai1 opens and the number of gates that control
      channel opening and conductance remain unclear. In this issue of Science
      Signaling, Frischauf et al report on the importance of the basic pore region in
      addition to the hydrophobic gate in channel gating and identify a site in
      transmembrane domain 2 (TM2) that controls pore opening.

PMID- 29184029
TI  - Update: Plant Cortical Microtubule Arrays.

PMID- 29184031
TI  - Transmembrane helix connectivity in Orai1 controls two gates for calcium
      dependent transcription.
AB  - The channel Orai1 requires Ca2+ store depletion in the endoplasmic reticulum and
      an interaction with the Ca2+ sensor STIM1 to mediate Ca2+ signaling. Alterations
      in Orai1-mediated Ca2+ influx have been linked to several pathological conditions
      including immunodeficiency, tubular myopathy, and cancer. We screened large-scale
      cancer genomics data sets for dysfunctional Orai1 mutants. Five of the identified
      Orai1 mutations resulted in constitutively active gating and transcriptional
      activation. Our analysis showed that certain Orai1 mutations were clustered in
      the transmembrane 2 helix surrounding the pore, which is a trigger site for Orai1
      channel gating. Analysis of the constitutively open Orai1 mutant channels
      revealed two fundamental gates that enabled Ca2+ influx: Arginine side chains
      were displaced so they no longer blocked the pore, and a chain of water molecules
      formed in the hydrophobic pore region. Together, these results enabled us to
      identify a cluster of Orai1 mutations that trigger Ca2+ permeation associated
      with gene transcription and provide a gating mechanism for Orai1.

PMID- 29184034
TI  - MEK inhibitor trametinib does not prevent the growth of anaplastic lymphoma
      kinase (ALK)-addicted neuroblastomas.
AB  - Activation of the RAS-RAF-MEK-ERK signaling pathway is implicated in driving the
      initiation and progression of multiple cancers. Several inhibitors targeting the
      RAS-MAPK pathway are clinically approved as single- or polyagent therapies for
      patients with specific types of cancer. One example is the MEK inhibitor
      trametinib, which is included as a rational polytherapy strategy for treating
      EML4-ALK-positive, EGFR-activated, or KRAS-mutant lung cancers and neuroblastomas
      that also contain activating mutations in the RAS-MAPK pathway. In addition, in
      neuroblastoma, a heterogeneous disease, relapse cases display an increased rate
      of mutations in ALK, NRAS, and NF1, leading to increased activation of RAS-MAPK
      signaling. Co-targeting ALK and the RAS-MAPK pathway is an attractive option,
      because monotherapies have not yet produced effective results in ALK-addicted
      neuroblastoma patients. We evaluated the response of neuroblastoma cell lines to
      MEK-ERK pathway inhibition by trametinib. In contrast to RAS-MAPK pathway-mutated
      neuroblastoma cell lines, ALK-addicted neuroblastoma cells treated with
      trametinib showed increased activation (inferred by phosphorylation) of the
      kinases AKT and ERK5. This feedback response was mediated by the mammalian target
      of rapamycin complex 2-associated protein SIN1, resulting in increased survival
      and proliferation that depended on AKT signaling. In xenografts in mice,
      trametinib inhibited the growth of EML4-ALK-positive non-small cell lung cancer
      and RAS-mutant neuroblastoma but not ALK-addicted neuroblastoma. Thus, our
      results advise against the seemingly rational option of using MEK inhibitors to
      treat ALK-addicted neuroblastoma.

PMID- 29184036
TI  - Retraction for Korczeniewska and Barnes, "The COP9 Signalosome Interacts with and
      Regulates Interferon Regulatory Factor 5 Protein Stability".

PMID- 29184033
TI  - Networks of enzymatically oxidized membrane lipids support calcium-dependent
      coagulation factor binding to maintain hemostasis.
AB  - Blood coagulation functions as part of the innate immune system by preventing
      bacterial invasion, and it is critical to stopping blood loss (hemostasis).
      Coagulation involves the external membrane surface of activated platelets and
      leukocytes. Using lipidomic, genetic, biochemical, and mathematical modeling
      approaches, we found that enzymatically oxidized phospholipids (eoxPLs) generated
      by the activity of leukocyte or platelet lipoxygenases (LOXs) were required for
      normal hemostasis and promoted coagulation factor activities in a Ca2+- and
      phosphatidylserine (PS)-dependent manner. In wild-type mice,
      hydroxyeicosatetraenoic acid-phospholipids (HETE-PLs) enhanced coagulation and
      restored normal hemostasis in clotting-deficient animals genetically lacking p12
      LOX or 12/15-LOX activity. Murine platelets generated 22 eoxPL species, all of
      which were missing in the absence of p12-LOX. Humans with the thrombotic disorder
      antiphospholipid syndrome (APS) had statistically significantly increased HETE
      PLs in platelets and leukocytes, as well as greater HETE-PL immunoreactivity,
      than healthy controls. HETE-PLs enhanced membrane binding of the serum protein
      beta2GP1 (beta2-glycoprotein 1), an event considered central to the autoimmune
      reactivity responsible for APS symptoms. Correlation network analysis of 47
      platelet eoxPL species in platelets from APS and control subjects identified
      their enzymatic origin and revealed a complex network of regulation, with the
      abundance of 31 p12-LOX-derived eoxPL molecules substantially increased in APS.
      In summary, circulating blood cells generate networks of eoxPL molecules,
      including HETE-PLs, which change membrane properties to enhance blood coagulation
      and contribute to the excessive clotting and immunoreactivity of patients with
      APS.

PMID- 29184035
TI  - Practice Variation in Acute Bronchiolitis: A Pediatric Emergency Research
      Networks Study.
AB  - BACKGROUND AND OBJECTIVES: Studies characterizing hospitalizations in
      bronchiolitis did not identify patients receiving evidence-based supportive
      therapies (EBSTs). We aimed to evaluate intersite and internetwork variation in
      receipt of >=1 EBSTs during the hospital management of infants diagnosed with
      bronchiolitis in 38 emergency departments of pediatric emergency research
      networks in Canada, the United States, Australia, New Zealand, the United
      Kingdom, Ireland, Spain, and Portugal. We hypothesized that there would be
      significant variation, adjusted for patient characteristics. METHODS:
      Retrospective cohort study of previously healthy infants aged <12 months with
      bronchiolitis. Our primary outcome was that hospitalization occurred with EBST
      (ie, parenteral fluids, oxygen, or airway support). RESULTS: Out of 3725
      participants, 1466 (39%) were hospitalized, and 1023 out of 1466 participants
      (69.8%) received EBST. The use of EBST varied by site (P < .001; range 6%-99%,
      median 23%), but not by network (P = .2). Significant multivariable predictors
      and their odds ratios (ORs) were as follows: age (0.9), oxygen saturation (1.3),
      apnea (3.4), dehydration (3.2), nasal flaring and/or grunting (2.4), poor feeding
      (2.1), chest retractions (1.9), and respiratory rate (1.2). The use of
      pharmacotherapy and radiography varied by network and site (P < .001), with
      respective intersite ranges 2% to 79% and 1.6% to 81%. Compared with Australia
      and New Zealand, the multivariable OR for the use of pharmacotherapy in Spain and
      Portugal was 22.7 (95% confidence interval [CI]: 4.5-111), use in Canada was 11.5
      (95% CI: 3.7-36), use in the United States was 6.8 (95% CI: 2.3-19.8), and use in
      the United Kingdom was 1.4 (95% CI: 0.4-4.2). Compared with United Kingdom, OR
      for radiography use in the United States was 4.9 (95% CI 2.0-12.2), use in Canada
      was 4.9 (95% CI 1.9-12.6), use in Spain and Portugal was 2.4 (95% CI 0.6-9.8),
      and use in Australia and New Zealand was 1.8 (95% CI 0.7-4.7). CONCLUSIONS: More
      than 30% of infants hospitalized with bronchiolitis received no EBST. The
      hospital site was a source of variation in all study outcomes, and the network
      also predicted the use of pharmacotherapy and radiography.

PMID- 29184037
TI  - Unusual Cause of Abdominal Pain and Anemia.

PMID- 29184038
TI  - Commentary.

PMID- 29184039
TI  - Commentary.

PMID- 29184040
TI  - A Term Newborn with Suspected Sepsis Following Prolonged Premature Rupture of
      Membranes.

PMID- 29184041
TI  - Green Serum After Parathyroidectomy.

PMID- 29184042
TI  - First Snowfall at Ancient Mountainous Wooden Walkways in China.

PMID- 29184043
TI  - Science in the Arts Series in Clinical Chemistry: Attempt at Conclusions.

PMID- 29184044
TI  - Intra-arterial oxidative stress correlates negatively with cognitive function and
      positively with postoperative ischemic lesions in carotid artery stenosis
      stenting.
AB  - BACKGROUND AND PURPOSE: Carotid plaque contains biologically active substances
      released into the blood during carotid artery stenting (CAS). The main purpose of
      this prospective study was to analyse sequential changes in oxidative stress
      during CAS and their relationship to clinical factors. METHODS: Twenty-two
      consecutive CAS procedures were performed between May 2014 and April 2016.
      Arterial blood was collected four times: (1) after the sheath insertion without
      edaravone; (2) pre-angioplasty with edaravone from the carotid artery; (3) after
      post-stenting angioplasty from an occluded carotid artery; and (4) before sheath
      removal. Derivatives of reactive oxygen metabolites (d-ROMs) and biological
      antioxidant potential (BAP) were measured photometrically. The relationship
      between d-ROMs or BAP and preoperatively investigated biochemical parameters,
      cognitive function, and number of diffusion-weighted image (DWI) high spot
      lesions was analysed using one-way ANOVA and the Tukey-Kramer HSD test. RESULTS:
      The d-ROM values for CAS were 355+/-58.8 Carratelli Units at sheath insertion,
      315+/-57.2 after edaravone infusion, 328+/-56.8 after post-stenting angioplasty,
      and 315+/-53.0 just before sheath removal. The d-ROM values were reduced
      significantly after edaravone infusion (P<0.05). The BAP at sheath insertion was
      reduced significantly according to age (P<0.05). The d-ROMs at sheath insertion
      correlated negatively with the dementia scale and positively with the post-CAS
      DWI high spots (1.00+/-1.07; P<0.05). Other biochemical parameters did not
      correlate with the d-ROM values or BAP. CONCLUSION: Oxidative stress is
      correlated negatively with cognitive function and positively with postoperative
      ischemic lesions. Antioxidant potential decreases with ageing.

PMID- 29184045
TI  - Cerebral arteriovenous malformation draining vein stenosis is associated with
      atherosclerotic risk factors.
AB  - OBJECTIVE: The pathogenesis of venous outflow stenosis associated with cerebral
      arteriovenous malformation (AVM) draining veins is poorly understood. We sought
      to determine the relationship between venous stenosis and atherosclerotic risk
      factors. MATERIALS AND METHODS: All patients with an AVM seen at our institution
      between 1990 and 2016 were retrospectively reviewed. Patients <18 years of age
      were excluded. Patients were classified into two groups based on the presence or
      absence of venous stenosis. Patient charts were reviewed for the following
      atherosclerotic risk factors: age >50 years, sex, race, hypertension, type 2
      diabetes mellitus, hyperlipidemia, coronary artery disease, chronic kidney
      disease stage III, and cigarette smoking. The relationship between venous
      stenosis and atherosclerotic risk factors was assessed using univariate and
      multivariate analyses. RESULTS: 278 patients were included (mean age 41 years,
      55% men). Venous stenosis was present in 87 patients (31% of the cohort). The
      presence of venous stenosis was significantly associated with age >50 years
      (P=0.05), hypertension (P=0.05), diabetes (P=0.02), and hyperlipidemia (P=0.001).
      Multivariate analysis showed that hyperlipidemia (P=0.05) was predictive of
      draining vein stenosis. CONCLUSIONS: Venous stenosis is associated with several
      atherosclerotic risk factors, suggesting that cerebral AVM venous outflow
      stenosis occurs by a degenerative process. Additional studies can show whether
      these modifiable risk factors may be targeted to prevent draining vein stenosis
      and AVM rupture.

PMID- 29184046
TI  - Decoding resistant hypertension signalling pathways.
AB  - Resistant hypertension (RH) is a clinical condition in which the hypertensive
      patient has become resistant to drug therapy and is often associated with
      increased cardiovascular morbidity and mortality. Several signalling pathways
      have been studied and related to the development and progression of RH:
      modulation of sympathetic activity by leptin and aldosterone, primary
      aldosteronism, arterial stiffness, endothelial dysfunction and variations in the
      renin-angiotensin-aldosterone system (RAAS). miRNAs comprise a family of small
      non-coding RNAs that participate in the regulation of gene expression at post
      transcriptional level. miRNAs are involved in the development of both
      cardiovascular damage and hypertension. Little is known of the molecular
      mechanisms that lead to development and progression of this condition. This
      review aims to cover the potential roles of miRNAs in the mechanisms associated
      with the development and consequences of RH, and explore the current state of the
      art of diagnostic and therapeutic tools based on miRNA approaches.

PMID- 29184047
TI  - The Impact of Using Non-Birth Sex on the Interpretation of Spirometry Data in
      Subjects With Air-Flow Obstruction.
AB  - BACKGROUND: Sex is an important determinant of lung capacity and function. This
      study examined the impact of using non-birth sex on the interpretation of
      spirometry data in transgender subjects with air-flow obstruction. METHODS: This
      study was a retrospective analysis of anonymous spirometry data. Eighty adult
      male and 80 adult female subjects were chosen from the database via random
      sampling. FVC, FEV1, and FEV1/FVC were collected and analyzed. Differences in
      percent of predicted, Z scores, classification of disease severity, and the
      incidence of a value migrating above or below the lower limit of normal between
      sex assignments were examined. RESULTS: For born male subjects, percent of
      predicted for FVC and FEV1 were significantly higher when the female sex was
      used: 100.5% versus 118.5% and 78% versus 91.5%, respectively (P < .001).
      FEV1/FVC Z score was -2.53 for male sex and -2.65 for female sex (P = .004). The
      presence of obstruction was not affected by sex assignment. Use of non-birth sex
      moved some FVC and FEV1 data above the lower limit of normal and improved
      severity classification in others. For born female subjects, percent of predicted
      for FVC and FEV1 were significantly lower when the male sex was used: 102% versus
      87.5% and 81.5% versus 70.5%, respectively (P < .001). FEV1/FVC Z score was -2.17
      for female sex and -2.12 for male sex (P < .001). Six born female subjects had
      their FEV1/FVC normalized when male sex was used. Use of non-birth sex moved some
      FVC and FEV1 data below the lower limit of normal and worsened severity
      classification in others. In total, using the non-birth sex affected spirometry
      interpretation in 45% of born male subjects and 70% of born female subjects.
      CONCLUSIONS: In transgender subjects with air-flow obstruction, using non-birth
      sex to calculate predicted spirometry values may have a significant impact on
      test interpretation and place these patients at risk for misdiagnosis and
      inappropriate treatment.

PMID- 29184048
TI  - Utilizing Respiratory Therapists to Reduce Costs of Care.
AB  - INTRODUCTION: Changes to the reimbursement of respiratory care services over the
      past 26 years make it imperative that respiratory therapists (RTs) demonstrate
      cost savings to establish their value. Therefore, this systematic review
      evaluated the cost-related impacts from utilizing RTs to deliver care when
      compared to other care providers. METHODS: The Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines were used to guide the search
      process. The study addressed articles across all age groups and care settings
      that compared the cost of care provided by RTs to a comparison group. Studies
      were excluded if they were not written in English, described care provided
      outside of the United States, did not provide quantitative data, or lacked a
      comparison group. RESULTS: A total of 4,120 articles emerged from the search
      process, of which 60 qualified for a full text review. Cost savings were
      evaluated for the 28 articles included in this review, noting the study design,
      the specific respiratory care practice, use of protocols, clinical setting, and
      age group. The most frequently studied topic was mechanical ventilation, which
      along with disease management represented by the most randomized, controlled
      trials for the study design. The clinical practice area notably absent was home
      care. CONCLUSIONS: Although cost comparisons across studies could not be made due
      to the inconsistent manner in which data were reported, evidence demonstrated
      that care provided by RTs yielded both direct and indirect cost reductions, which
      were achieved through protocol utilization, specialized expertise, and autonomous
      decision making. The care provided was consistent with care provided by other
      disciplines. It is critical for the respiratory care profession to highlight key
      clinical practice areas for future research, to establish uniform reporting
      measures for outcomes, and to foster the development of future respiratory care
      researchers to affirm the value that respiratory therapists add to patient care.

PMID- 29184049
TI  - Does Diaphragmatic Electrical Activity in Preterm Infants Predict Extubation
      Success?
AB  - BACKGROUND: Despite many advances in respiratory care and mechanical ventilation,
      neonatologists lack an objective tool to aid in decision making for timely
      extubation. Electrical activity of the diaphragm (EAdi), a measure of neural
      respiratory drive and inspiratory load, may be a useful predictor of extubation
      success in preterm neonates. The objective of this work was to investigate
      whether peak EAdi could distinguish successful versus failed extubation in
      mechanically ventilated preterm infants. METHODS: We examined peak EAdi as a
      predictor of extubation outcome in a convenience sample of 21 preterm infants
      with respiratory distress syndrome requiring mechanical ventilation. Infants were
      ventilated with a VN500 ventilator using volume guarantee mode and extubated per
      unit protocol. Peak EAdi was continuously measured with an EAdi catheter in the
      esophagus to obtain data at 1-min intervals for 24 h before extubation. The
      primary outcome was extubation success, defined as not requiring re-intubation
      for at least 72 h. RESULTS: Twenty one premature infants with respiratory
      distress syndrome included in the study had a mean +/- SD) gestational age of 28
      +/- 2.6 weeks and mean birthweight of 1,208 +/- 611 g. The first extubation
      attempt occurred at a median age of 1 d (interquartile range 1-2 d). One third of
      the infants failed the first extubation attempt. Infants with failed extubations
      were significantly smaller (mean +/- SD birthweight 788 +/- 266 g versus 1,417 +/
      632 g) and of lower gestational age (mean +/- SD 26 +/- 1.9 weeks versus 29 +/-
      2.6 weeks) compared with those with successful extubation. Mean peak EAdi before
      extubation did not differ between the 2 groups. CONCLUSIONS: This small study
      suggests that the pre-extubation peak EAdi does not predict extubation success.
      (ClinicalTrials.gov registration NCT02144363.).

PMID- 29184050
TI  - A Rare Case of Bochdalek Hernia with Concomitant Para-Esophageal Hernia, Repaired
      Laparoscopically in an Octogenarian.
AB  - BACKGROUND A Bochdalek hernia (BH) is a rare congenital condition consisting of a
      posterolateral defect in the diaphragm. A para-esophageal hernia (PEH) is a rare
      variant of hiatus hernia. BH and PEH may present with gastric volvulus or
      incarceration, requiring emergency treatment. Minimally invasive surgery is the
      preferred treatment, particularly for elderly patients and patients with
      comorbidities. The occurrence of BH with concomitant PEH is a very rare event. We
      describe a case of an octogenarian patient with BH and concomitant PEH treated
      laparoscopically. CASE REPORT An 81-year-old male patient, without significant
      comorbidities, presented with a two-month history of severe chest pain and
      vomiting after eating. Cardiological investigations ruled out cardiac ischemia,
      infarction, or other cardiovascular abnormalities. Chest and abdominal computed
      tomography (CT) imaging demonstrated a large diaphragmatic hernia, with the
      entire stomach in the left thorax. Laboratory results showed mild anemia and a
      low iron level. The patient underwent simultaneous laparoscopic repair of a BH
      and a PEH with mesh reinforcement without antireflux fundoplication. The
      patient's postoperative recovery was uneventful. CONCLUSIONS We have presented a
      rare case of BH with concomitant PEH in an octogenarian that was successfully
      treated with laparoscopic surgery. Although these two forms of hernia are a very
      rare association, this case report illustrates that the surgical approach should
      be individualized in each patient's case to ensure a successful surgical outcome.
      In this case, the decision was made to suture the diaphragmatic crura and
      reinforce the diaphragm repair with mesh, rather than by fundoplication.

PMID- 29184051
TI  - Clinical Efficacy of Anterior Partial Corpectomy and Titanium Mesh Fusion and
      Internal Fixation for Treatment of Old Fracture Dislocation of the Lower Cervical
      Spine.
AB  - BACKGROUND The aim of this study was to analyze the clinical features and to
      evaluate the efficacy of anterior partial corpectomy and titanium mesh fusion and
      internal fixation of old fracture dislocation of the lower cervical spine.
      MATERIAL AND METHODS We retrospectively analyzed the clinical data of 52 patients
      with old lower cervical fracture and dislocation treated with anterior partial
      corpectomy and titanium mesh fusion fixation between January 2008 and December
      2013, with a mean follow-up period of 4.1 years. There were 35 males and 17
      females. Patient radiological data and clinical parameters were recorded and
      compared before and after the operations. RESULTS The average follow-up was 4.1
      years. Intervertebral height and physiological curvature were well-reconstructed
      for all cases. No loosening or rupturing of titanium plate or screw occurred. The
      neurological function of the patients with incomplete spinal cord injury was
      significantly improved, and the function of the nerve roots at the injury level
      was also improved in patients with complete spinal cord injury. Bone fusion was
      completed within 6 months to 1 year after surgery. CONCLUSIONS Completed
      decompression, sequence and physiological curvature of the cervical vertebra,
      immediate and long-term anterior cervical column support, and nerve function
      restoration can be achieved by using anterior partial corpectomy and titanium
      mesh fusion and internal fixation to treat old fracture dislocation of the lower
      cervical spine. For cases with locked facet joints or posterior structures
      invading the vertebral canal, the combined anterior and posterior approaches
      should be performed, when necessary, to achieve better results.

PMID- 29184053
TI  - A Co3O4-CDots-C3N4 three component electrocatalyst design concept for efficient
      and tunable CO2 reduction to syngas.
AB  - Syngas, a CO and H2 mixture mostly generated from non-renewable fossil fuels, is
      an essential feedstock for production of liquid fuels. Electrochemical reduction
      of CO2 and H+/H2O is an alternative renewable route to produce syngas. Here we
      introduce the concept of coupling a hydrogen evolution reaction (HER) catalyst
      with a CDots/C3N4 composite (a CO2 reduction catalyst) to achieve a cheap,
      stable, selective and efficient route for tunable syngas production. Co3O4, MoS2,
      Au and Pt serve as the HER component. The Co3O4-CDots-C3N4 electrocatalyst is
      found to be the most efficient among the combinations studied. The H2/CO ratio of
      the produced syngas is tunable from 0.07:1 to 4:1 by controlling the potential.
      This catalyst is highly stable for syngas generation (over 100 h) with no other
      products besides CO and H2. Insight into the mechanisms balancing between CO2
      reduction and H2 evolution when applying the HER-CDots-C3N4 catalyst concept is
      provided.

PMID- 29184052
TI  - Notch transactivates Rheb to maintain the multipotency of TSC-null cells.
AB  - Differentiation abnormalities are a hallmark of tuberous sclerosis complex (TSC)
      manifestations; however, the genesis of these abnormalities remains unclear. Here
      we report on mechanisms controlling the multi-lineage, early neuronal progenitor
      and neural stem-like cell characteristics of lymphangioleiomyomatosis (LAM) and
      angiomyolipoma cells. These mechanisms include the activation of a previously
      unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic binding of Notch1
      to the Notch-responsive elements (NREs) on the Rheb promoter is a key event. This
      binding induces the transactivation of Rheb. The identified NRE2 and NRE3 on the
      Rheb promoter are important to Notch-dependent promoter activity. Notch
      cooperates with Rheb to block cell differentiation via similar mechanisms in
      mouse models of TSC. Cell-specific loss of Tsc1 within nestin-expressing cells in
      adult mice leads to the formation of kidney cysts, renal intraepithelial
      neoplasia, and invasive papillary renal carcinoma.

PMID- 29184054
TI  - Meta-analysis of the interaction between serotonin transporter promoter variant,
      stress, and posttraumatic stress disorder.
AB  - Exposure to stress predicts the occurrence of posttraumatic stress disorder
      (PTSD) in individuals harboring the serotonin transporter promoter variant 5
      HTTLPR. We carried out a meta-analysis of studies investigating the interaction
      between 5-HTTLPR, stress, and PTSD to clarify the interrelatedness of these
      factors. We reviewed all relevant studies published in English before May 2016.
      The Liptak-Stouffer z-score method for meta-analysis was applied to combined
      data. The z score was separately calculated for the stressful life events,
      childhood adversity, bi- and triallelic loci, and cross-sectional and
      longitudinal studies subgroups. A total of 14 studies with 15,883 subjects met
      our inclusion criteria. We found strong evidence that the presence of 5-HTTLPR
      influenced the relationship between stress and PTSD (P = 0.00003), with the
      strongest effects observed in the cross-sectional and longitudinal groups (P =
      0.01 and 2.0 * 10-6, respectively). Stressful life events and childhood adversity
      separately interacted with 5-HTTLPR in PTSD (P = 2.0 * 10-8 and 0.003,
      respectively). When the studies were stratified by locus classification, the
      evidence was stronger for the triallelic (P = 4.0 * 10-8) than for the biallelic
      (P = 0.054) locus subgroup. There was strong evidence that 5-HTTLPR influences
      the relationship between stress and PTSD.

PMID- 29184055
TI  - Giant barocaloric effects over a wide temperature range in superionic conductor
      AgI.
AB  - Current interest in barocaloric effects has been stimulated by the discovery that
      these pressure-driven thermal changes can be giant near ferroic phase transitions
      in materials that display magnetic or electrical order. Here we demonstrate giant
      inverse barocaloric effects in the solid electrolyte AgI, near its superionic
      phase transition at ~420 K. Over a wide range of temperatures, hydrostatic
      pressure changes of 2.5 kbar yield large and reversible barocaloric effects,
      resulting in large values of refrigerant capacity. Moreover, the peak values of
      isothermal entropy change (60 J K-1 kg-1 or 0.34 J K-1 cm-3) and adiabatic
      temperature changes (18 K), which we identify for a starting temperature of 390
      K, exceed all values previously recorded for barocaloric materials. Our work
      should therefore inspire the study of barocaloric effects in a wide range of
      solid electrolytes, as well as the parallel development of cooling devices.

PMID- 29184056
TI  - Functional mapping and annotation of genetic associations with FUMA.
AB  - A main challenge in genome-wide association studies (GWAS) is to pinpoint
      possible causal variants. Results from GWAS typically do not directly translate
      into causal variants because the majority of hits are in non-coding or intergenic
      regions, and the presence of linkage disequilibrium leads to effects being
      statistically spread out across multiple variants. Post-GWAS annotation
      facilitates the selection of most likely causal variant(s). Multiple resources
      are available for post-GWAS annotation, yet these can be time consuming and do
      not provide integrated visual aids for data interpretation. We, therefore,
      develop FUMA: an integrative web-based platform using information from multiple
      biological resources to facilitate functional annotation of GWAS results, gene
      prioritization and interactive visualization. FUMA accommodates positional,
      expression quantitative trait loci (eQTL) and chromatin interaction mappings, and
      provides gene-based, pathway and tissue enrichment results. FUMA results directly
      aid in generating hypotheses that are testable in functional experiments aimed at
      proving causal relations.

PMID- 29184057
TI  - The effects of PI3K-mediated signalling on glioblastoma cell behaviour.
AB  - The PI3K/Akt/mTOR signalling network is activated in almost 90% of all
      glioblastoma, the most common primary brain tumour, which is almost invariably
      lethal within 15 months of diagnosis. Despite intensive research, modulation of
      this signalling cascade has so far yielded little therapeutic benefit, suggesting
      that the role of the PI3K network as a pro-survival factor in glioblastoma and
      therefore a potential target in combination therapy should be re-evaluated.
      Therefore, we used two distinct pharmacological inhibitors that block signalling
      at different points of the cascade, namely, GDC-0941 (Pictilisib), a direct
      inhibitor of the near apical PI3K, and Rapamycin which blocks the side arm of the
      network that is regulated by mTOR complex 1. While both substances, at
      concentrations where they inhibit their primary target, have similar effects on
      proliferation and sensitisation for temozolomide-induced apoptosis, GDC-0941
      appears to have a stronger effect on cellular motility than Rapamycin. In vivo
      GDC-0941 effectively retards growth of orthotopic transplanted human tumours in
      murine brains and significantly prolongs mouse survival. However, when looking at
      genetically identical cell populations that are in alternative states of
      differentiation, i.e. stem cell-like cells and their differentiated progeny, a
      more complex picture regarding the PI3K/Akt/mTOR pathway emerges. The pathway is
      differently regulated in the alternative cell populations and, while it
      contributes to the increased chemo-resistance of stem cell-like cells compared to
      differentiated cells, it only contributes to the motility of the latter. Our
      findings are the first to suggest that within a glioblastoma tumour the PI3K
      network can have distinct, cell-specific functions. These have to be carefully
      considered when incorporating inhibition of PI3K-mediated signals into complex
      combination therapies.

PMID- 29184058
TI  - Doxycycline induces apoptosis via ER stress selectively to cells with a cancer
      stem cell-like properties: importance of stem cell plasticity.
AB  - Tumor heterogeneity can be traced back to a small subset of cancer stem cells
      (CSCs), which can be derived from a single stem cell and show chemoresistance.
      Recent studies showed that CSCs are sensitive to mitochondrial targeting
      antibiotics such as doxycycline. However, little is known about how cancer cells
      undergo sphere formation and how antibiotics inhibit CSC proliferation. Here we
      show that under sphere-forming assay conditions, prostate cancer cells acquired
      CSC-like properties: promoted mitochondrial respiratory chain activity,
      expression of characteristic CSC markers and resistance to anticancer agents.
      Furthermore, those CSC-like properties could reversibly change depending on the
      culture conditions, suggesting some kinds of CSCs have plasticity in tumor
      microenvironments. The sphere-forming cells (i.e. cancer stem-like cells) showed
      increased contact between mitochondria and mitochondrial associated-endoplasmic
      reticulum (ER) membranes (MAM). Mitochondrial targeting doxycycline induced
      activating transcription factor 4 (ATF4) mediated expression of ER stress
      response and led to p53-upregulated modulator of apoptosis (PUMA)-dependent
      apoptosis only in the cancer stem-like cells. We also found that doxycycline
      effectively suppressed the sphere formation in vitro and blocked CD44v9
      expressing tumor growth in vivo. In summary, these data provide new molecular
      findings that monolayer cancer cells acquire CSC-like properties in a reversible
      manner. These findings provide important insights into CSC biology and a
      potential new treatment of targeting mitochondria dependency.

PMID- 29184060
TI  - Predictive feedback to V1 dynamically updates with sensory input.
AB  - Predictive coding theories propose that the brain creates internal models of the
      environment to predict upcoming sensory input. Hierarchical predictive coding
      models of vision postulate that higher visual areas generate predictions of
      sensory inputs and feed them back to early visual cortex. In V1, sensory inputs
      that do not match the predictions lead to amplified brain activation, but does
      this amplification process dynamically update to new retinotopic locations with
      eye-movements? We investigated the effect of eye-movements in predictive feedback
      using functional brain imaging and eye-tracking whilst presenting an apparent
      motion illusion. Apparent motion induces an internal model of motion, during
      which sensory predictions of the illusory motion feed back to V1. We observed
      attenuated BOLD responses to predicted stimuli at the new post-saccadic location
      in V1. Therefore, pre-saccadic predictions update their retinotopic location in
      time for post-saccadic input, validating dynamic predictive coding theories in
      V1.

PMID- 29184059
TI  - Cardiopatch platform enables maturation and scale-up of human pluripotent stem
      cell-derived engineered heart tissues.
AB  - Despite increased use of human induced pluripotent stem cell-derived
      cardiomyocytes (hiPSC-CMs) for drug development and disease modeling studies,
      methods to generate large, functional heart tissues for human therapy are
      lacking. Here we present a "Cardiopatch" platform for 3D culture and maturation
      of hiPSC-CMs that after 5 weeks of differentiation show robust electromechanical
      coupling, consistent H-zones, I-bands, and evidence for T-tubules and M-bands.
      Cardiopatch maturation markers and functional output increase during culture,
      approaching values of adult myocardium. Cardiopatches can be scaled up to
      clinically relevant dimensions, while preserving spatially uniform properties
      with high conduction velocities and contractile stresses. Within window chambers
      in nude mice, cardiopatches undergo vascularization by host vessels and continue
      to fire Ca2+ transients. When implanted onto rat hearts, cardiopatches robustly
      engraft, maintain pre-implantation electrical function, and do not increase the
      incidence of arrhythmias. These studies provide enabling technology for future
      use of hiPSC-CM tissues in human heart repair.

PMID- 29184061
TI  - Metal-hydrogen systems with an exceptionally large and tunable thermodynamic
      destabilization.
AB  - Hydrogen is a key element in the energy transition. Hydrogen-metal systems have
      been studied for various energy-related applications, e.g., for their use in
      reversible hydrogen storage, catalysis, hydrogen sensing, and rechargeable
      batteries. These applications depend strongly on the thermodynamics of the metal
      hydrogen system. Therefore, tailoring the thermodynamics of metal-hydrogen
      interactions is crucial for tuning the properties of metal hydrides. Here we
      present a case of large metal hydride destabilization by elastic strain. The
      addition of small amounts of zirconium to yttrium leads to a compression of the
      yttrium lattice, which is maintained during (de)hydrogenation cycles. As a
      result, the equilibrium hydrogen pressure of YH2 <-> YH3 can be rationally and
      precisely tuned up to five orders of magnitude at room temperature. This allows
      us to realize a hydrogen sensor which indicates the ambient hydrogen pressure
      over four orders of magnitude by an eye-visible color change.

PMID- 29184062
TI  - Molecular architecture of potassium chloride co-transporter KCC2.
AB  - KCC2 is a neuron specific K+-Cl- co-transporter that controls neuronal chloride
      homeostasis, and is critically involved in many neurological diseases including
      brain trauma, epilepsies, autism and schizophrenia. Despite significant
      accumulating data on the biology and electrophysiological properties of KCC2,
      structure-function relationships remain poorly understood. Here we used
      calixarene detergent to solubilize and purify wild-type non-aggregated and
      homogenous KCC2. Specific binding of inhibitor compound VU0463271 was
      demonstrated using surface plasmon resonance (SPR). Mass spectrometry revealed
      glycosylations and phosphorylations as expected from functional KCC2. We show by
      electron microscopy (EM) that KCC2 exists as monomers and dimers in solution.
      Monomers are organized into "head" and "core" domains connected by a flexible
      "linker". Dimers are asymmetrical and display a bent "S-shape" architecture made
      of four distinct domains and a flexible dimerization interface. Chemical
      crosslinking in reducing conditions shows that disulfide bridges are involved in
      KCC2 dimerization. Moreover, we show that adding a tag to the C-terminus is
      detrimental to KCC2 function. We postulate that the conserved KCC2 C-ter may be
      at the interface of dimerization. Taken together, our findings highlight the
      flexible multi-domain structure of KCC2 with variable anchoring points at the
      dimerization interface and an important C-ter extremity providing the first in
      depth functional architecture of KCC2.

PMID- 29184063
TI  - Phloem-limited reoviruses universally induce sieve element hyperplasia and more
      flexible gateways, providing more channels for their movement in plants.
AB  - Virion distribution and ultrastructural changes induced by the infection of maize
      or rice with four different reoviruses were examined. Rice black streaked dwarf
      virus (RBSDV, genus Fijivirus), Rice ragged stunt virus (RRSV, genus Oryzavirus),
      and Rice gall dwarf virus (RGDV, genus Phytoreovirus) were all phloem-limited and
      caused cellular hyperplasia in the phloem resulting in tumors or vein swelling
      and modifying the cellular arrangement of sieve elements (SEs). In contrast,
      virions of Rice dwarf virus (RDV, genus Phytoreovirus) were observed in both
      phloem and mesophyll and the virus did not cause hyperplasia of SEs. The three
      phloem-limited reoviruses (but not RDV) all induced more flexible gateways at the
      SE-SE interfaces, especially the non-sieve plate interfaces. These flexible
      gateways were also observed for the first time at the cellular interfaces between
      SE and phloem parenchyma (PP). In plants infected with any of the reoviruses,
      virus-like particles could be seen within the flexible gateways, suggesting that
      these gateways may serve as channels for the movement of plant reoviruses with
      their large virions between SEs or between SEs and PP. SE hyperplasia and the
      increase in flexible gateways may be a universal strategy for the movement of
      phloem-limited reoviruses.

PMID- 29184064
TI  - Low-threshold optically pumped lasing in highly strained germanium nanowires.
AB  - The integration of efficient, miniaturized group IV lasers into CMOS architecture
      holds the key to the realization of fully functional photonic-integrated
      circuits. Despite several years of progress, however, all group IV lasers
      reported to date exhibit impractically high thresholds owing to their
      unfavourable bandstructures. Highly strained germanium with its fundamentally
      altered bandstructure has emerged as a potential low-threshold gain medium, but
      there has yet to be a successful demonstration of lasing from this seemingly
      promising material system. Here we demonstrate a low-threshold, compact group IV
      laser that employs a germanium nanowire under a 1.6% uniaxial tensile strain as
      the gain medium. The amplified material gain in strained germanium can
      sufficiently overcome optical losses at 83 K, thus allowing the observation of
      multimode lasing with an optical pumping threshold density of ~3.0 kW cm-2. Our
      demonstration opens new possibilities for group IV lasers for photonic-integrated
      circuits.

PMID- 29184066
TI  - The sensitivity of donor - acceptor charge transfer to molecular geometry in DAN 
      NDI based supramolecular flower-like self-assemblies.
AB  - A charge-transfer (CT) complex self-assembled from an electron acceptor (NDI-EA:
      naphthalene diimide with appended diamine) and an electron donor (DAN: phosphonic
      acid-appended dialkoxynapthalene) in aqueous medium. The aromatic core of the NDI
      and the structure of DAN1 were designed to optimize the dispersive interactions
      (pi-pi and van der Waals interactions) in the DAN1-NDI-EA self-assembly, while
      the amino groups of NDI also interact with the phosphonic acid of DAN1 via
      electrostatic forces. This arrangement prevented crystallization and favored the
      directional growth of 3D flower nanostructures. This molecular geometry that is
      necessary for charge transfer to occur was further evidenced by using a
      mismatching DAN2 structure. The flower-shaped assembly was visualized by scanning
      electron and transmission electron microscopy. The formation of the CT complex
      was determined by UV-vis and cyclic voltammetry and the photoinduced electron
      transfer to produce the radical ion pair was examined by femtosecond laser
      transient absorption spectroscopic measurements.

PMID- 29184065
TI  - Zero-field edge plasmons in a magnetic topological insulator.
AB  - Incorporating ferromagnetic dopants into three-dimensional topological insulator
      thin films has recently led to the realisation of the quantum anomalous Hall
      effect. These materials are of great interest since they may support electrical
      currents that flow without resistance, even at zero magnetic field. To date, the
      quantum anomalous Hall effect has been investigated using low-frequency transport
      measurements. However, transport results can be difficult to interpret due to the
      presence of parallel conductive paths, or because additional non-chiral edge
      channels may exist. Here we move beyond transport measurements by probing the
      microwave response of a magnetised disk of Cr-(Bi,Sb)2Te3. We identify features
      associated with chiral edge plasmons, a signature that robust edge channels are
      intrinsic to this material system. Our results provide a measure of the velocity
      of edge excitations without contacting the sample, and pave the way for an on
      chip circuit element of practical importance: the zero-field microwave
      circulator.

PMID- 29184067
TI  - Identification of a neural crest stem cell niche by Spatial Genomic Analysis.
AB  - The neural crest is an embryonic population of multipotent stem cells that form
      numerous defining features of vertebrates. Due to lack of reliable techniques to
      perform transcriptional profiling in intact tissues, it remains controversial
      whether the neural crest is a heterogeneous or homogeneous population. By
      coupling multiplex single molecule fluorescence in situ hybridization with
      machine learning algorithm based cell segmentation, we examine expression of 35
      genes at single cell  resolution in vivo. Unbiased hierarchical clustering
      reveals five spatially distinct subpopulations within the chick dorsal neural
      tube. Here we identify a neural crest stem cell niche that centers around the
      dorsal midline with high expression of neural crest genes, pluripotency factors,
      and lineage markers. Interestingly, neural and neural crest stem cells express
      distinct pluripotency signatures. This Spatial Genomic Analysis toolkit provides
      a straightforward approach to study quantitative multiplex gene expression in
      numerous biological systems, while offering insights into gene regulatory
      networks via synexpression analysis.

PMID- 29184068
TI  - Heterologous expression reveals the biosynthesis of the antibiotic pleuromutilin
      and generates bioactive semi-synthetic derivatives.
AB  - The rise in antibiotic resistance is a major threat for human health.
      Basidiomycete fungi represent an untapped source of underexploited
      antimicrobials, with pleuromutilin-a diterpene produced by Clitopilus
      passeckerianus-being the only antibiotic from these fungi leading to commercial
      derivatives. Here we report genetic characterisation of the steps involved in
      pleuromutilin biosynthesis, through rational heterologous expression in
      Aspergillus oryzae coupled with isolation and detailed structural elucidation of
      the pathway intermediates by spectroscopic methods and comparison with synthetic
      standards. A. oryzae was further established as a platform for bio-conversion of
      chemically modified analogues of pleuromutilin intermediates, and was employed to
      generate a semi-synthetic pleuromutilin derivative with enhanced antibiotic
      activity. These studies pave the way for future characterisation of biosynthetic
      pathways of other basidiomycete natural products in ascomycete heterologous
      hosts, and open up new possibilities of further chemical modification for the
      growing class of potent pleuromutilin antibiotics.

PMID- 29184069
TI  - Phosphorylated exogenous alpha-synuclein fibrils exacerbate pathology and induce
      neuronal dysfunction in mice.
AB  - Approximately 90% of alpha-synuclein (alpha-Synuclein) deposited in Lewy bodies
      is phosphorylated at serine 129 suggesting that the accumulation of
      phosphorylated alpha-Synuclein is critical in the pathogenesis of Parkinson's
      disease. However, in vivo experiments addressing the role of phosphorylated alpha
      Synuclein in the progression of Parkinson's disease have produced equivocal data.
      To clarify a role of Ser129 phosphorylation of alpha-Synuclein in pathology
      progression we performed stereotaxic injections targeting the mouse striatum with
      three fibrilar alpha-Synuclein types: wt-fibrils, phosphorylated S129 fibrils
      and, phosphorylation incompetent, S129A fibrils. Brain inoculation of all three
      fibrilar types caused seeding of the endogenous alpha-Synuclein. However,
      phosphorylated fibrils triggered the formation of more alpha-Synuclein inclusions
      in the Substantia Nigra pars compacta (SNpc), exacerbated pathology in the cortex
      and caused dopaminergic neuronal loss and fine motor impairment as early as 60
      days post injection. Phosphorylated fibril injections also induced early changes
      in the innate immune response including alterations in macrophage recruitment and
      IL-10 release. Our study further shows that S129 phosphorylation facilitated
      alpha-Synuclein fibril uptake by neurons. Our results highlight the role of
      phosphorylated fibrilar alpha-Synuclein in pathology progression in vivo and
      suggest that targeting phosphorylated alpha-Synuclein assemblies might be
      important for delaying inclusion formation.

PMID- 29184070
TI  - Improved outcome for AML patients over the years 2000-2014.
AB  - Few recent studies from registries have reported an improvement in overall
      survival of younger patients with acute myeloid leukemia (AML). However, reasons
      for this improvement are not defined. We analyzed the therapeutic course and
      outcome of 976 patients treated by intensive chemotherapy between 2000 and 2014.
      The number of patients receiving allogeneic stem cell transplantation in first or
      second response significantly increased over time whereas autologous
      transplantation was progressively abandoned. In the 513 younger patients, there
      were no differences in first complete response, induction failure, incidence of
      relapse, or non-relapse mortality over time. The period of time was significantly
      associated with a better overall survival especially in 2010-2014. The 2010-2014
      period effect was still significant in multivariate analysis and was independent
      of allogeneic stem cell transplantation. In the 463 older patients, there was a
      significant interaction between the period and leukocytosis in multivariate
      analysis meaning that the 2010-2014 period had only an impact in patients with
      white blood cell count >50 giga/L for response and overall survival. Progresses
      have been made in each phase of the therapeutic course of younger AML patients
      resulting in survival improvement. In older patients, the outcome of
      hyperleukocytic patients has significantly improved in 2010-2014.

PMID- 29184071
TI  - Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits
      from DSS colitis but may be detrimental under conditions of immunosuppression.
AB  - Trichuris suis ova (TSO) have been tested for therapeutic application in
      inflammatory bowel diseases (IBD) yet understanding of the underlying mechanisms
      and safety in an immunocompromised host is limited due to lack of a suitable
      animal model. We used a recently established rabbit model of dextran sodium
      sulphate (DSS) induced colitis to study the efficacy, mechanisms and safety of
      TSO therapy in immunocompetent and immunosuppressed animals. TSO treatment
      prevented the DSS induced weight loss, delayed the onset of DSS induced symptoms
      by 2 days and significantly reduced the disease activity (DAI). TSO treatment
      protected caecal histology and prevented the colitis-associated loss in faecal
      microbiota diversity. Mainly the transcriptome of lamina propria mononuclear
      cells (LPMC) was affected by TSO treatment, showing dampened innate and adaptive
      inflammatory responses. The protective effect of TSO was lost in immunosuppressed
      rabbits, where TSO exacerbated colitis. Our data show that preventive TSO
      treatment ameliorates colitis severity in immunocompetent rabbits, modulates LPMC
      immune responses and reduces faecal dysbiosis. In contrast, the same TSO
      treatment exacerbates colitis in immunosuppressed animals. Our data provide
      further evidence for a therapeutic effect of TSO in IBD, yet caution is required
      with regard to TSO treatment in immunosuppressed patients.

PMID- 29184072
TI  - Adrenomedullin protects Leydig cells against lipopolysaccharide-induced oxidative
      stress and inflammatory reaction via MAPK/NF-kappaB signalling pathways.
AB  - This study aimed to explore the possible benefits of adrenomedullin (ADM) in
      preventing oxidative stress and inflammation by using an in vitro primary culture
      model of rat Leydig cells exposed to lipopolysaccharide (LPS). Cell proliferation
      was detected through CCK-8 and BrdU incorporation assays. ROS were determined
      with a DCFDA kit, and cytokine concentrations were measured with ELISA assay
      kits. Protein production was examined by immunohistochemical staining and Western
      blot, and gene expression was observed through RT-qPCR. Results revealed that ADM
      significantly reduced LPS-induced cytotoxicity, and pretreatment with ADM
      significantly suppressed ROS overproduction and decreased 4-HNE and 8-OHdG
      expression levels and concentrations. ADM pretreatment also significantly
      attenuated the overactivation of enzymatic antioxidants, namely, superoxide
      dismutase, catalase, thioredoxin reductase, glutathione peroxidase, glutathione
      reductase and glutathione-S-transferase. ADM supplementation reversed the
      significantly increased gene expression levels and concentrations of TNF-alpha,
      IL-1beta, TGF-beta1, MCP-1 and MIF. ADM pretreatment significantly inhibited the
      gene expression and protein production of TLR-2 and 4. Furthermore, ADM
      pretreatment markedly reduced the phosphorylation of JNK, ERK 1/2 and p38,
      phosphorylation and degradation of IkappaBalpha and nuclear translocation of p65.
      Our findings demonstrated that ADM protects Leydig cells from LPS-induced
      oxidative stress and inflammation, which might be associated with MAPK/NF-kappaB
      signalling pathways.

PMID- 29184073
TI  - Simple spatial scaling rules behind complex cities.
AB  - Although most of wealth and innovation have been the result of human interaction
      and cooperation, we are not yet able to quantitatively predict the spatial
      distributions of three main elements of cities: population, roads, and
      socioeconomic interactions. By a simple model mainly based on spatial attraction
      and matching growth mechanisms, we reveal that the spatial scaling rules of these
      three elements are in a consistent framework, which allows us to use any single
      observation to infer the others. All numerical and theoretical results are
      consistent with empirical data from ten representative cities. In addition, our
      model can also provide a general explanation of the origins of the universal
      super- and sub-linear aggregate scaling laws and accurately predict kilometre
      level socioeconomic activity. Our work opens a new avenue for uncovering the
      evolution of cities in terms of the interplay among urban elements, and it has a
      broad range of applications.

PMID- 29184074
TI  - Scaling relationships and theory for vibrational frequencies of adsorbates on
      transition metal surfaces.
AB  - Adsorbate vibrational excitations are an important fingerprint of
      molecule/surface interactions, affecting temperature contributions to the free
      energy and impacting reaction rate and equilibrium constants. Furthermore,
      vibrational spectra aid in identifying species and adsorption sites present in
      experimental studies. Despite their importance, knowledge of how adsorbate
      frequencies scale across materials is lacking. Here, by combining previously
      reported experimental data and our own density-functional theory calculations, we
      reveal linear correlations between vibrational frequencies of adsorbates on
      transition metal surfaces. Through effective-medium theory, linear muffin-tin
      orbital theory, and the d-band model, we rationalize the squares of the
      frequencies to be fundamentally linear in their scaling across transition metal
      surfaces. We identify the adsorbate-binding energy as a descriptor for certain
      molecular vibrations and rigorously relate errors in frequencies to errors in
      adsorption energies. We also discuss the impact of scaling on surface
      thermochemistry and adsorbate coverage.

PMID- 29184075
TI  - Subdiffusion via dynamical localization induced by thermal equilibrium
      fluctuations.
AB  - We reveal the mechanism of subdiffusion which emerges in a straightforward, one
      dimensional classical nonequilibrium dynamics of a Brownian ratchet driven by
      both a time-periodic force and Gaussian white noise. In a tailored parameter set
      for which the deterministic counterpart is in a non-chaotic regime, subdiffusion
      is a long-living transient whose lifetime can be many, many orders of magnitude
      larger than characteristic time scales of the setup thus being amenable to
      experimental observations. As a reason for this subdiffusive behaviour in the
      coordinate space we identify thermal noise induced dynamical localization in the
      velocity (momentum) space. This novel idea is distinct from existing knowledge
      and has never been reported for any classical or quantum system. It suggests
      reconsideration of generally accepted opinion that subdiffusion is due to broad
      distributions or strong correlations which reflect disorder, trapping,
      viscoelasticity of the medium or geometrical constraints.

PMID- 29184076
TI  - Deciphering how Cpl-7 cell wall-binding repeats recognize the bacterial
      peptidoglycan.
AB  - Endolysins, the cell wall lytic enzymes encoded by bacteriophages to release the
      phage progeny, are among the top alternatives to fight against multiresistant
      pathogenic bacteria; one of the current biggest challenges to global health.
      Their narrow range of susceptible bacteria relies, primarily, on targeting
      specific cell-wall receptors through specialized modules. The cell wall-binding
      domain of Cpl-7 endolysin, made of three CW_7 repeats, accounts for its extended
      range of substrates. Using as model system the cell wall-binding domain of Cpl-7,
      here we describe the molecular basis for the bacterial cell wall recognition by
      the CW_7 motif, which is widely represented in sequences of cell wall hydrolases.
      We report the crystal and solution structure of the full-length domain, identify
      N-acetyl-D-glucosaminyl-(beta1,4)-N-acetylmuramyl-L-alanyl-D-isoglutamine (GMDP)
      as the peptidoglycan (PG) target recognized by the CW_7 motifs, and characterize
      feasible GMDP-CW_7 contacts. Our data suggest that Cpl-7 cell wall-binding domain
      might simultaneously bind to three PG chains, and also highlight the potential
      use of CW_7-containing lysins as novel anti-infectives.

PMID- 29184077
TI  - The structural, magnetic and optical properties of TMn@(ZnO)42 (TM = Fe, Co and
      Ni) hetero-nanostructure.
AB  - The magnetic transition-metal (TM) @ oxide nanoparticles have been of great
      interest due to their wide range of applications, from medical sensors in
      magnetic resonance imaging to photo-catalysis. Although several studies on small
      clusters of TM@oxide have been reported, the understanding of the physical
      electronic properties of TMn@(ZnO)42 is far from sufficient. In this work, the
      electronic, magnetic and optical properties of TMn@(ZnO)42 (TM = Fe, Co and Ni)
      hetero-nanostructure are investigated using the density functional theory (DFT).
      It has been found that the core-shell nanostructure Fe13@(ZnO)42, Co15@(ZnO)42
      and Ni15@(ZnO)42 are the most stable structures. Moreover, it is also predicted
      that the variation of the magnetic moment and magnetism of Fe, Co and Ni in
      TMn@ZnO42 hetero-nanostructure mainly stems from effective hybridization between
      core TM-3d orbitals and shell O-2p orbitals, and a magnetic moment inversion for
      Fe15@(ZnO)42 is investigated. Finally, optical properties studied by calculations
      show a red shift phenomenon in the absorption spectrum compared with the case of
      (ZnO)48.

PMID- 29184078
TI  - Function of capric acid in cyclophosphamide-induced intestinal inflammation,
      oxidative stress, and barrier function in pigs.
AB  - The small intestine is not only critical for nutrient absorption, but also serves
      as an important immune organ. Medium-chain fatty acids have nutritional and
      metabolic effects and support the integrity of the intestinal epithelium.
      However, their roles in intestinal immunity in pigs are not fully understood. We
      investigated the effects of a medium-chain fatty acid, capric acid, on intestinal
      oxidative stress, inflammation, and barrier function in porcine epithelial cells
      and miniature pigs after treatment with the immune suppressant cyclophosphamide.
      Capric acid alleviated inflammatory cytokine production (TNF-alpha and IL-6) and
      related gene expression (NF-kappaB, TNF-alpha, IFN-gamma), alleviated oxidative
      stress (GSSG/GSH ratio, H2O2, and malondialdehyde), and increased oxidative
      stress-related gene expression (SOD1 and GCLC) in cyclophosphamide-treated IPEC
      J2 cells. The permeability of FD-4 and expression of ZO-1 and OCLN in
      cyclophosphamide-treated IPEC-J2 cells were reduced by capric acid. Dietary
      capric acid reduced TNF-alpha, IL-6, and MDA levels and increased SOD, GPx, and
      the expression of genes related to pro-inflammatory, oxidative stress, and
      intestinal barrier functions in cyclophosphamide-treated miniature pigs. These
      results revealed that capric acid has protective effects against cyclophosphamide
      induced small intestinal dysfunction in pigs.

PMID- 29184079
TI  - Virus-host protein-protein interactions of mycobacteriophage Giles.
AB  - Mycobacteriophage are viruses that infect mycobacteria. More than 1,400
      mycobacteriophage genomes have been sequenced, coding for over one hundred
      thousand proteins of unknown functions. Here we investigate mycobacteriophage
      Giles-host protein-protein interactions (PPIs) using yeast two-hybrid screening
      (Y2H). A total of 25 reproducible PPIs were found for a selected set of 10 Giles
      proteins, including a putative virion assembly protein (gp17), the phage
      integrase (gp29), the endolysin (gp31), the phage repressor (gp47), and six
      proteins of unknown function (gp34, gp35, gp54, gp56, gp64, and gp65). We note
      that overexpression of the proteins is toxic to M. smegmatis, although whether
      this toxicity and the associated changes in cellular morphology are related to
      the putative interactions revealed in the Y2H screen is unclear.

PMID- 29184080
TI  - Factors affecting pitch discrimination performance in a cohort of extensively
      phenotyped healthy volunteers.
AB  - Despite efforts to characterize the different aspects of musical abilities in
      humans, many elements of this complex area remain unknown. Musical abilities are
      known to be associated with factors like intelligence, training, and sex, but a
      comprehensive evaluation of the simultaneous impact of multiple factors has not
      yet been performed. Here, we assessed 918 healthy volunteers for pitch
      discrimination abilities-their ability to tell two tones close in pitch apart. We
      identified the minimal threshold that the participants could detect, and we found
      that better performance was associated with higher intelligence, East Asian
      ancestry, male sex, younger age, formal music training-especially before age 6
      and English as the native language. All these factors remained significant when
      controlling for the others, with general intelligence, musical training, and male
      sex having the biggest impacts. We also performed a small GWAS and gene-based
      collapsing analysis, identifying no significant associations. Future genetic
      studies of musical abilities should involve large sample sizes and an unbiased
      genome-wide approach, with the factors highlighted here included as important
      covariates.

PMID- 29184081
TI  - Allosteric inhibitor remotely modulates the conformation of the orthestric
      pockets in mutant IDH2/R140Q.
AB  - Neomorphic mutation R140Q in the metabolic enzyme isocitrate dehydrogenase 2
      (IDH2) is found to be a driver mutation in cancers. Recent studies revealed that
      allosteric inhibitors could selectively inhibit IDH2/R140Q and induce
      differentiation of TF-1 erythroleukemia and primary human AML cells. However, the
      allosteric inhibition mechanism is not very clear. Here, we report the results
      from computational studies that AGI-6780 binds tightly with the divalent cation
      binding helices at the homodimer interface and prevents the transition of
      IDH2/R140Q homodimer to a closed conformation that is required for catalysis,
      resulting in the decrease of the binding free energy of NADPHs. If the allosteric
      inhibitor is removed, the original open catalytic center of IDH2/R140Q will
      gradually reorganize to a quasi-closed conformation and the enzymatic activity
      might recover. Unlike IDH2/R140Q, AGI-6780 locks one monomer of the wild-type
      IDH2 in an inactive open conformation and the other in a half-closed
      conformation, which can be used to explain the selectivity of AGI-6780. Our
      results suggest that conformational changes are the primary contributors to the
      inhibitory potency of the allosteric inhibitor. Our study will also facilitate
      the understanding of the inhibitory and selective mechanisms of AG-221 (a
      promising allosteric inhibitor that has been approved by FDA) for mutant IDH2.

PMID- 29184082
TI  - Identification of a histone family gene signature for predicting the prognosis of
      cervical cancer patients.
AB  - Heterogeneity in terms of tumor characteristics, prognosis, and survival among
      cancer patients is an unsolved issue. Here, we systematically analyzed the
      aberrant expression patterns of cervical cancer using RNA-Seq data from The
      Cancer Genome Atlas (TCGA). We incorporated gene profiling, molecular signatures,
      functional and pathway information with gene set enrichment and protein-protein
      interaction (PPI) network analysis, to identify sub-networks of genes. Those
      identified genes relating to DNA replication and DNA repair-mediated signaling
      pathways associated with systemic lupus erythematosus (SLE). Next, we combined
      cross-validated prognostic scores to build an integrated prognostic model for
      survival prediction. The combined approach revealed that the DNA repair-mediated
      including the functional interaction module of 18 histone genes (Histone cluster
      1 H2A, B and H4), were significantly correlated with the survival rate.
      Furthermore, five of these histone genes were highly expressed in three cervical
      cancer cohorts from the Oncomine database. Comparison of high and low histone
      variant-expressing human cervical cancer cell lines revealed different responses
      to DNA damage, suggesting protective functions of histone genes against DNA
      damage. Collectively, we provide evidence that two SLE-associated gene sets
      (HIST1H2BD and HIST1H2BJ; and HIST1H2BD, HIST1H2BJ, HIST1H2BH, HIST1H2AM and
      HIST1H4K) can be used as prognostic factors for survival prediction among
      cervical cancer patients.

PMID- 29184083
TI  - The power of monitoring: optimizing survey designs to detect occupancy changes in
      a rare amphibian population.
AB  - Biodiversity conservation requires reliable species assessments and rigorously
      designed surveys. However, determining the survey effort required to reliably
      detect population change can be challenging for rare, cryptic and elusive
      species. We used a tropical bromeliad-dwelling frog as a model system to explore
      a cost-effective sampling design that optimizes the chances of detecting a
      population decline. Relatively few sampling visits were needed to estimate
      occupancy and detectability with good precision, and to detect a 30% change in
      occupancy with 80% power. Detectability was influenced by observer expertise,
      which therefore also had an effect on the sampling design - less experienced
      observers require more sampling visits to detect the species. Even when the
      sampling design provides precise parameter estimates, only moderate to large
      changes in occupancy will be detected with reliable power. Detecting a population
      change of 15% or less requires a large number of sites to be surveyed, which
      might be unachievable for range-restricted species occurring at relatively few
      sites. Unless there is high initial occupancy, rare and cryptic species will be
      particularly challenging when it comes to detecting small population changes.
      This may be a particular issue for long-term monitoring of amphibians which often
      display low detectability and wide natural fluctuations.

PMID- 29184084
TI  - The flexibility and dynamics of the tubules in the endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) is a single organelle in eukaryotic cells that
      extends throughout the cell and is involved in a large number of cellular
      functions. Using a combination of fixed and live cells (human MRC5 lung cells) in
      diffraction limited and super-resolved fluorescence microscopy (STORM)
      experiments, we determined that the average persistence length of the ER tubules
      was 3.03 +/- 0.24 MUm. Removing the branched network junctions from the analysis
      caused a slight increase in the average persistence length to 4.71 +/- 0.14 MUm,
      and provides the tubule's persistence length with a moderate length scale
      dependence. The average radius of the tubules was 44.1 +/- 3.2 nm. The bending
      rigidity of the ER tubule membranes was found to be 10.9 +/- 1.2 kT (17.0 +/- 1.3
      kT without branch points). We investigated the dynamic behaviour of ER tubules in
      live cells, and found that the ER tubules behaved like semi-flexible fibres under
      tension. The majority of the ER tubules experienced equilibrium transverse
      fluctuations under tension, whereas a minority number of them had active super
      diffusive motions driven by motor proteins. Cells thus actively modulate the
      dynamics of the ER in a well-defined manner, which is expected in turn to impact
      on its many functions.

PMID- 29184085
TI  - Diverse Changes of Circulating Fibroblast Growth Factor 21 Levels in Hepatitis B
      Virus-Related Diseases.
AB  - Fibroblast growth factor 21 (FGF21), a stress-induced hormone in the liver, has
      been shown the protective functions in pathological conditions. The study
      investigated the association of circulating FGF21 with hepatitis B virus (HBV)
      infection and its related diseases. Serum FGF21 levels were measured in 33 acute
      hepatitis B (AHB), 75 chronic hepatitis B (CHB) and 66 CHB patients with advanced
      liver diseases including liver cirrhosis, acute-on-chronic liver failure (ALCF)
      and hepatocellular carcinoma (HCC) together with 200 age- and BMI-matched healthy
      controls. FGF21 levels were significantly increased in AHB patients and rapidly
      returned to normal levels after treatment. FGF21 levels reflected the degree of
      liver injury caused by AHB. However, serum FGF21 levels were decreased in CHB
      patients especially in those who developed cirrhosis and were associated with
      hepatic protein synthesis capacity. Serum FGF21 in CHB patients were increased
      with the occurrence of ACLF. Notably, in CHB patients who developed HCC, serum
      FGF21 exhibited a dramatic increase, which may provide important information on
      monitoring tumorigenesis in CHB patients. In conclusion, we revealed the diverse
      changes of circulating FGF21 in HBV-related diseases. FGF21 may be a useful
      biomarker in monitoring the tumorigenesis in patients with CHB.

PMID- 29184086
TI  - Characteristic of entire corneal topography and tomography for the detection of
      sub-clinical keratoconus with Zernike polynomials using Pentacam.
AB  - The study aimed to characterize the entire corneal topography and tomography for
      the detection of sub-clinical keratoconus (KC) with a Zernike application method.
      Normal subjects (n = 147; 147 eyes), sub-clinical KC patients (n = 77; 77 eyes),
      and KC patients (n = 139; 139 eyes) were imaged with the Pentacam HR system. The
      entire corneal data of pachymetry and elevation of both the anterior and
      posterior surfaces were exported from the Pentacam HR software. Zernike
      polynomials fitting was used to quantify the 3D distribution of the corneal
      thickness and surface elevation. The root mean square (RMS) values for each order
      and the total high-order irregularity were calculated. Multimeric discriminant
      functions combined with individual indices were built using linear step
      discriminant analysis. Receiver operating characteristic curves determined the
      diagnostic accuracy (area under the curve, AUC). The 3rd-order RMS of the
      posterior surface (AUC: 0.928) obtained the highest discriminating capability in
      sub-clinical KC eyes. The multimeric function, which consisted of the Zernike
      fitting indices of corneal posterior elevation, showed the highest discriminant
      ability (AUC: 0.951). Indices generated from the elevation of posterior surface
      and thickness measurements over the entire cornea using the Zernike method based
      on the Pentacam HR system were able to identify very early KC.

PMID- 29184087
TI  - A half-site multimeric enzyme achieves its cooperativity without conformational
      changes.
AB  - Cooperativity is a feature many multimeric proteins use to control activity. Here
      we show that the bacterial heptose isomerase GmhA displays homotropic positive
      and negative cooperativity among its four protomers. Most similar proteins
      achieve this through conformational changes: GmhA instead employs a delicate
      network of hydrogen bonds, and couples pairs of active sites controlled by a
      unique water channel. This network apparently raises the Lewis acidity of the
      catalytic zinc, thus increasing the activity at one active site at the cost of
      preventing substrate from adopting a reactive conformation at the paired
      negatively cooperative site - a "half-site" behavior. Our study establishes the
      principle that multimeric enzymes can exploit this cooperativity without
      conformational changes to maximize their catalytic power and control. More
      broadly, this subtlety by which enzymes regulate functions could be used to
      explore new inhibitor design strategies.

PMID- 29184088
TI  - Comparison of two-year outcomes after photodynamic therapy with ranibizumab or
      aflibercept for polypoidal choroidal vasculopathy.
AB  - Photodynamic therapy (PDT) combined with intravitreal anti-vascular endothelial
      growth factor (VEGF) agents is currently the first-line treatment for polypoidal
      choroidal vasculopathy (PCV), along with anti-VEGF monotherapy. In this study,
      100 eyes with treatment-naive PCV were initially treated with PDT combined with
      intravitreal ranibizumab (IVR; n = 57) or aflibercept (IVA; n = 43). We compared
      two-year outcomes between these two groups and investigated factors associated
      with visual improvement and retreatment over 24 months. Best-corrected visual
      acuity (BCVA) was significantly improved in both groups (P < 0.001) at 24 months.
      Multiple regression analysis revealed that visual improvement at 24 months was
      associated with female (P = 0.030), worse baseline BCVA (P = 3.0 * 10-6), smaller
      greatest linear dimension (GLD; P = 2.0 * 10-4), and treatment with IVA rather
      than IVR (P = 0.016). Multiple logistic regression analysis revealed that absence
      of retreatment was associated with younger age (P = 2.2 * 10-4), female (P = 1.2
      * 10-3), and the non-risk variants of ARMS2 A69S (P = 6.0 * 10-4). Although there
      were no significant differences in the retreatment rate between the two groups,
      PDT/IVA may be superior to PDT/IVR in terms of visual improvement at 24 months.

PMID- 29184089
TI  - Topological States Characterized by Mirror Winding Numbers in Graphene with Bond
      Modulation.
AB  - Localized electrons appear at the zigzag-shaped edge of graphene due to quantum
      interference. Here we propose a way for harnessing the edge electronic states to
      make them mobile, by incorporating a topological view point. The manipulation
      required is to introduce a pattern of strong-weak bonds between neighboring
      carbon atoms, and to put side by side two graphene sheets with strong-weak
      alternation conjugating to each other. The electrons with up and down pseudospins
      propagate in opposite directions at the interface, similar to the prominent
      quantum spin Hall effect. The system is characterized by a topological index, the
      mirror winding number, with its root lying in the Su-Schrieffer-Heeger model for
      polymer. Taking this point of view, one is rewarded by several ways for
      decorating graphene edge which result in similar mobile electronic states with
      topological protection. This work demonstrates that celebrated nanotechnology can
      be used to derive topological states.

PMID- 29184090
TI  - Thyroid hormones derivatives reduce proliferation and induce cell death and DNA
      damage in ovarian cancer.
AB  - Ovarian cancer is a highly aggressive disease and novel treatments are required.
      Thyroid hormones binding to alphavbeta3 integrin produced growth-promoting
      activities in ovarian cancer and we hypothesized that natural thyroid hormone
      derivatives may antagonize these actions. The effect of three antagonists,
      tetraiodoacetic acid (tetrac), triiodothyroacetic acid (triac) and 3
      iodothyronamine (T1AM), on cell proliferation, cell death and DNA damage was
      studied in two ovarian cancer cell lines (OVCAR3 and A2780), normal hamster ovary
      control cells (CHOK1) and alphavbeta3-deficient or transfected HEK293 cells. A
      differential inhibition of cell proliferation was observed in ovarian cancer
      cells compared to CHOK1. In OVCAR3, an induction of cell cycle regulators was
      further shown. Apoptosis was confirmed (annexin-PI, SubG1/cell-cycle, apoptotic
      genes, caspase-3 and poly ADP ribose polymerase-1 (PARP-1) cleavage) and was
      reversed by a pan-caspase inhibitor. Induction in apoptosis inducing factor (AIF)
      was observed, suggesting a parallel caspase-independent mechanism. Integrin
      involvement in triac/T1AM apoptotic action was shown in alphavbeta3-transfected
      HEK293 cells. Lastly, in ovarian cancer models, key proteins that coordinate
      recognition of DNA damage, ataxia-telangiectasia mutated (ATM) and PARP-1, were
      induced. To conclude, the cytotoxic potential of thyroid hormone derivatives,
      tetrac, triac and T1AM, in ovarian cancer may provide a much-needed novel
      therapeutic approach.

PMID- 29184091
TI  - 2D/3D Microanalysis by Energy Dispersive X-ray Absorption Spectroscopy
      Tomography.
AB  - X-ray spectroscopic techniques have proven to be particularly useful in
      elucidating the molecular and electronic structural information of chemically
      heterogeneous and complex micro- and nano-structured materials. However,
      spatially resolved chemical characterization at the micrometre scale remains a
      challenge. Here, we report the novel hyperspectral technique of micro Energy
      Dispersive X-ray Absorption Spectroscopy (MUED-XAS) tomography which can resolve
      in both 2D and 3D the spatial distribution of chemical species through the
      reconstruction of XANES spectra. To document the capability of the technique in
      resolving chemical species, we first analyse a sample containing 2-30 MUm grains
      of various ferrous- and ferric-iron containing minerals, including hypersthene,
      magnetite and hematite, distributed in a light matrix of a resin. We accurately
      obtain the XANES spectra at the Fe K-edge of these four standards, with spatial
      resolution of 3 MUm. Subsequently, a sample of ~1.9 billion-year-old microfossil
      from the Gunflint Formation in Canada is investigated, and for the first time
      ever, we are able to locally identify the oxidation state of iron compounds
      encrusting the 5 to 10 MUm microfossils. Our results highlight the potential for
      attaining new insights into Precambrian ecosystems and the composition of Earth's
      earliest life forms.

PMID- 29184092
TI  - Simple eco-friendly synthesis of the surfactant free SnS nanocrystal toward the
      photoelectrochemical cell application.
AB  - A simple, low cost, non-toxic and eco-friendly pathway for synthesizing efficient
      sunlight-driven tin sulfide photocatalyst was studied. SnS nanocrystals were
      prepared by using mechanical method. The bulk SnS was obtained by evaporation of
      SnS nanocrystal solution. The synthesized samples were characterized by using
      XRD, SEM, TEM, UV-vis, and Raman analyses. Well crystallized SnS nanocrystals
      were verified and the electrochemical characterization was also performed under
      visible light irradiation. The SnS nanocrystals have shown remarkable
      photocurrent density of 7.6 mA cm-2 under 100 mW cm-2 which is about 10 times
      larger than that of the bulk SnS under notably stable operation conditions.
      Furthermore, the SnS nanocrystals presented higher stability than the bulk form.
      The IPCE(Incident photon to current conversion efficiency) of 9.3% at 420 nm was
      obtained for SnS nanocrystal photoanode which is strikingly higher than that of
      bulk SnS, 0.78%. This work suggests that the enhancement of reacting area by
      using SnS nanocrystal absorbers could give rise to the improvement of
      photoelectrochemical cell efficiency.

PMID- 29184093
TI  - Intrapartum antibiotics for GBS prophylaxis alter colonization patterns in the
      early infant gut microbiome of low risk infants.
AB  - Early life microbial colonization and succession is critically important to
      healthy development with impacts on metabolic and immunologic processes
      throughout life. A longitudinal prospective cohort was recruited from midwifery
      practices to include infants born at full term gestation to women with
      uncomplicated pregnancies. Here we compare bacterial community succession in
      infants born vaginally, with no exposure to antibiotics (n = 53), with infants
      who were exposed to intrapartum antibiotic prophylaxis (IAP) for Group B
      Streptococcus (GBS; n = 14), and infants born by C-section (n = 7). Molecular
      profiles  of the 16 S rRNA genes indicate that there is a delay in the expansion
      of Bifidobacterium, which was the dominate infant gut colonizer, over the first
      12 weeks and a persistence of Escherichia when IAP for GBS exposure is present
      during vaginal labour. Longer duration of IAP exposure increased the magnitude of
      the effect on Bifidobacterium populations, suggesting a longer delay in microbial
      community maturation. As with prior studies, we found altered gut colonisation
      following C-section that included a notable lack of Bacteroidetes. This study
      found that exposure of infants to IAP for GBS during vaginal birth affected
      aspects of gut microbial ecology that, although dramatic at early time points,
      disappeared by 12 weeks of age in most infants.

PMID- 29184094
TI  - Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface.
AB  - Antibiotic efflux is one of the most critical mechanisms leading to bacterial
      multidrug resistance. Antibiotics are effluxed out of the bacterial cell by a
      tripartite efflux pump, a complex machinery comprised of outer membrane,
      periplasmic adaptor, and inner membrane protein components. Understanding the
      mechanism of efflux pump assembly and its dynamics could facilitate discovery of
      novel approaches to counteract antibiotic resistance in bacteria. We built here
      an intact atomistic model of the Pseudomonas aeruginosa MexAB-OprM pump in a Gram
      negative membrane model that contained both inner and outer membranes separated
      by a periplasmic space. All-atom molecular dynamics (MD) simulations confirm that
      the fully assembled pump is stable in the microsecond timescale. Using a
      combination of all-atom and coarse-grained MD simulations and sequence
      covariation analysis, we characterized the interface between MexA and OprM in the
      context of the entire efflux pump. These analyses suggest a plausible mechanism
      by which OprM is activated via opening of its periplasmic aperture through a
      concerted interaction with MexA.

PMID- 29184095
TI  - Exteroceptive expectations modulate interoceptive processing: repetition
      suppression effects for visual and heartbeat evoked potentials.
AB  - Interoception refers to the signaling of internal bodily commands. Here, we
      explore repetition suppression of intero- and exteroceptive neural markers to
      test whether the perception and predictability of exteroceptive stimulus material
      affects their expression. Participants completed a repetition suppression
      paradigm in which angry or neutral facial expressions repeated or alternated.
      Participants received either an implicit (experiment 1) or explicit (experiment
      2) cue enabling the formation of expectations regarding the upcoming facial
      expression. We measured the heartbeat-evoked potential (HEP) indexing cardiac
      processing and visual evoked potentials (VEP) in response to viewing the second
      (repeated or alternated) face. Repeating angry facial expressions produced
      repetition suppression of both HEP and VEP amplitude while repeating neutral
      expressions led to repetition enhancement of HEP amplitude. This effect was
      magnified when participants were explicitly aware of predictive cues.
      Furthermore, repetition suppression of HEP amplitude correlated with neural
      attenuation of VEP activity. Results highlight repetition effects for
      interoceptive as well as exteroceptive neural markers and support top-down,
      expectation-based accounts of the phenomenon. Furthermore, results demonstrate
      that the perception of exteroceptive stimulus information has an effect on the
      processing of interoceptive signals and suggest a direct neural connection
      between the processing of external and internal sensory information.

PMID- 29184096
TI  - Development of corticostriatal connectivity constrains goal-directed behavior
      during adolescence.
AB  - When pursuing high-value goals, mature individuals typically titrate cognitive
      performance according to environmental demands. However, it remains unclear
      whether adolescents similarly integrate value-based goals to selectively enhance
      goal-directed behavior. We used a value-contingent cognitive control task during
      fMRI to assess how stakes-the value of a prospective outcome-modulate flexible
      goal-directed behavior and underlying neurocognitive processes. Here we
      demonstrate that while adults enhance performance during high stakes, adolescents
      perform similarly during low and high stakes conditions. The developmental
      emergence of value-contingent performance is mediated by connectivity between the
      striatum and prefrontal cortex; this connectivity selectively increases during
      high stakes and with age. These findings suggest that adolescents may not benefit
      from high stakes to the same degree adults do-a behavioral profile that may be
      constrained by ongoing maturation of corticostriatal connectivity. We propose
      that late development of corticostriatal connectivity sets the stage for optimal
      goal-directed behavior.

PMID- 29184097
TI  - Csl2, a novel chimeric bacteriophage lysin to fight infections caused by
      Streptococcus suis, an emerging zoonotic pathogen.
AB  - Streptococcus suis is a Gram-positive bacterium that infects humans and various
      animals, causing human mortality rates ranging from 5 to 20%, as well as
      important losses for the swine industry. In addition, there is no effective
      vaccine for S. suis and isolates with increasing antibiotic multiresistance are
      emerging worldwide. Facing this situation, wild type or engineered bacteriophage
      lysins constitute a promising alternative to conventional antibiotics. In this
      study, we have constructed a new chimeric lysin, Csl2, by fusing the catalytic
      domain of Cpl-7 lysozyme to the CW_7 repeats of LySMP lysin from an S. suis
      phage. Csl2 efficiently kills different S. suis strains and shows noticeable
      activity against a few streptococci of the mitis group. Specifically, 15 ug/ml
      Csl2 killed 4.3 logs of S. suis serotype 2 S735 strain in 60 min, in a buffer
      containing 150 mM NaCl and 10 mM CaCl2, at pH 6.0. We have set up a protocol to
      form a good biofilm with the non-encapsulated S. suis mutant strain BD101, and
      the use of 30 ug/ml Csl2 was enough for dispersing such biofilms and reducing 1-2
      logs the number of planktonic bacteria. In vitro results have been validated in
      an adult zebrafish model of infection.

PMID- 29184098
TI  - Counter-intuitive influence of Himalayan river morphodynamics on Indus
      Civilisation urban settlements.
AB  - Urbanism in the Bronze-age Indus Civilisation (~4.6-3.9 thousand years before the
      present, ka) has been linked to water resources provided by large Himalayan river
      systems, although the largest concentrations of urban-scale Indus settlements are
      located far from extant Himalayan rivers. Here we analyse the sedimentary
      architecture, chronology and provenance of a major palaeochannel associated with
      many of these settlements. We show that the palaeochannel is a former course of
      the Sutlej River, the third largest of the present-day Himalayan rivers. Using
      optically stimulated luminescence dating of sand grains, we demonstrate that flow
      of the Sutlej in this course terminated considerably earlier than Indus
      occupation, with diversion to its present course complete shortly after ~8 ka.
      Indus urban settlements thus developed along an abandoned river valley rather
      than an active Himalayan river. Confinement of the Sutlej to its present incised
      course after ~8 ka likely reduced its propensity to re-route frequently thus
      enabling long-term stability for Indus settlements sited along the relict
      palaeochannel.

PMID- 29184099
TI  - Accurate quantification of homologous recombination in zebrafish: brca2
      deficiency as a paradigm.
AB  - Homologous Recombination (HR) repair is essential for repairing DNA double strand
      breaks (DSB) in dividing cells and preventing tumorigenesis. BRCA2 plays an
      important role in HR by recruiting the DNA recombinase RAD51 to the DSB. Despite
      being a popular model organism in genetic and cancer research, knowledge on the
      conservation of the HR pathway and function of zebrafish Brca2 is limited. To
      evaluate this, we developed a Rad51 foci assay in zebrafish embryos. We
      identified the zebrafish embryonic intestinal tissue as an ideal target for Rad51
      immunostaining. After inducing DSB through irradiation, Rad51 foci were present
      in irradiated embryos but not in unirradiated controls. We present a method for
      accurate quantification of HR. Both morpholino-induced knockdown and knockout of
      Brca2 lead to almost complete absence of Rad51 foci in irradiated embryos. These
      findings indicate conserved function of Brca2 in zebrafish. Interestingly, a
      statistically significant decrease in Rad51 foci was observed in Brca2
      heterozygous carriers compared to wild types, indicative of haploinsufficiency, a
      hypothesised cause of some tumours in patients with a germline BRCA2 mutation. In
      conclusion, we demonstrated the suitability of zebrafish as an excellent in vivo
      model system for studying the HR pathway and its functionality.

PMID- 29184100
TI  - AKT-mTOR signaling modulates the dynamics of IRE1 RNAse activity by regulating ER
      mitochondria contacts.
AB  - Inositol Requiring Enzyme-1 (IRE1) is the most conserved transducer of the
      Unfolded Protein Response (UPR), a surveillance mechanism that ensures
      homeostasis of the endoplasmic reticulum (ER) in eukaryotes. IRE1 activation
      orchestrates adaptive responses, including lipid anabolism, metabolic
      reprogramming, increases in protein folding competency, and ER
      expansion/remodeling. However, we still know surprisingly little regarding the
      principles by which this ER transducer is deactivated upon ER stress clearance.
      Here we show that Protein Kinase B-mechanistic Target of Rapamycin (PKB/AKT-mTOR)
      signaling controls the dynamics of IRE1 deactivation by regulating ER
      mitochondria physical contacts and the autophosphorylation state of IRE1. AKT
      mTOR-mediated attenuation of IRE1 activity is important for ER remodelling
      dynamics and cell survival in the face of recursive, transient ER stress. Our
      observations suggest that IRE1 attenuation is an integral component of anabolic
      programmes regulated by AKT-mTOR. We suggest that AKT-mTOR activity is part of a
      'timing mechanism' to deactivate IRE1 immediately following engagement of the
      UPR, in order to limit prolonged IRE1 RNAse activity that could lead to damaging
      inflammation or apoptosis.

PMID- 29184101
TI  - A meta-proteomics approach to study the interspecies interactions affecting
      microbial biofilm development in a model community.
AB  - Microbial biofilms are omnipresent in nature and relevant to a broad spectrum of
      industries ranging from bioremediation and food production to biomedical
      applications. To date little is understood about how multi-species biofilm
      communities develop and function on a molecular level, due to the complexity of
      these biological systems. Here we apply a meta-proteomics approach to investigate
      the mechanisms influencing biofilm formation in a model consortium of four
      bacterial soil isolates; Stenotrophomonas rhizophila, Xanthomonas retroflexus,
      Microbacterium oxydans and Paenibacillus amylolyticus. Protein abundances in
      community and single species biofilms were compared to describe occurring inter
      species interactions and the resulting changes in active metabolic pathways. To
      obtain full taxonomic resolution between closely related species and empower
      correct protein quantification, we developed a novel pipeline for generating
      reduced reference proteomes for spectral database searches. Meta-proteomics
      profiling indicated that community development is dependent on cooperative
      interactions between community members facilitating cross-feeding on specific
      amino acids. Opposite regulation patterns of fermentation and nitrogen pathways
      in Paenibacillus amylolyticus and Xanthomonas retroflexus may, however, indicate
      that competition for limited resources also affects community development.
      Overall our results demonstrate the multitude of pathways involved in biofilm
      formation in mixed communities.

PMID- 29184102
TI  - Pressure-induced magnetic moment abnormal increase in Mn2FeAl and non-continuing
      decrease in Fe2MnAl via first principles.
AB  - The magnetism of Fe2MnAl and Mn2FeAl compounds are studied by first principles.
      Evolutions of magnetic moment of Fe2MnAl display distinct variation trends under
      pressure, showing three different slopes at different pressure intervals, 0~100
      GPa, 100~250 GPa, 250-400 GPa, respectively, and the moment collapses finally at
      450 GPa. The magnetic moment of Mn2FeAl shows an increasing tendency below 40 GPa
      and decreases subsequently with pressure, and collapses ultimately at about 175
      GPa. Such non-continuing decrease of Fe2MnAl originates from the unusual charge
      transfer of Fe and Mn and bond populations rearrangement of Fe-Fe and Mn-Fe,
      whereas the distinct moment evolution of Mn2FeAl is attributed to the complicated
      distributions of bond populations. The half-metallicity of the compounds can be
      maintained at low pressure, below about 100 GPa in Fe2MnAl and 50 GPa in Mn2FeAl.
      The magnetic moment collapse process didn't induce volume and bond length
      anomalies in the two compounds, the unique anomaly is the elastic softening
      behaviour in elastic constant c 44 and shear (G) and Young's (E) moduli of
      Fe2MnAl at 270 GPa, where the second moment collapse occurs.

PMID- 29184103
TI  - Inconsistency in the Crown-to-Root Ratios of Single-Rooted Premolars Measured by
      2D and 3D Examinations.
AB  - Micro-computed tomography (micro-CT) was applied to elucidate the relationship
      between the three-dimensional (3D) root surface area (RSA) and two-dimensional
      (2D) crown-to-root ratio (CRR) of extracted teeth to classify the periodontitis
      and assign a periodontal/prosthetic prognosis. A total of 31 maxillary and 35
      mandibular single-rooted human premolars were examined. The amount of periodontal
      support on the basis of 3D RSA and 2D root length (RL) at CRRs of 1:1, 5:4, 3:2,
      and 2:1 were analyzed. Both maxillary and mandibular premolars demonstrated a
      nonsignificant RSA percentage at the evaluated CRRs. The coronal 21%-22% 2D RL
      and the 26%-28% 3D RSA bone loss apical to the cemento-enamel junction
      corresponded to a CRR of 1:1, relating to mild-moderate periodontitis. The
      coronal 30%-31% 2D RL and the 41%-42% 3D RSA bone loss corresponded to a CRR of
      5:4, correlating to severe periodontitis. More severe clinical attachment loss
      (CAL) was observed in the 3D RSA measurement than in the 2D RL measurement at the
      evaluated CRRs. The amount of CAL at the CRR of 1:1 was inadequate to assess the
      severity of periodontitis on the basis of the 2D RL and 3D RSA measurements.

PMID- 29184104
TI  - Dynamic modulation of the perceptual load on microsaccades during a selective
      spatial attention task.
AB  - Selective spatial attention enhances task performance at restricted regions
      within the visual field. The magnitude of this effect depends on the level of
      attentional load, which determines the efficiency of distractor rejection.
      Mechanisms of attentional load include perceptual selection and/or cognitive
      control involving working memory. Recent studies have provided evidence that
      microsaccades are influenced by spatial attention. Therefore, microsaccade
      activities may be exploited to help understand the dynamic control of selective
      attention under different load levels. However, previous reports in humans on the
      effect of attentional load on microsaccades are inconsistent, and it is not clear
      to what extent these results and the dynamic changes of microsaccade activities
      are similar in monkeys. We trained monkeys to perform a color detection task in
      which the perceptual load was manipulated by task difficulty with limited
      involvement of working memory. Our results indicate that during the task with
      high perceptual load, the rate and amplitude of microsaccades immediately before
      the target color change were significantly suppressed. We also found that the
      occurrence of microsaccades before the monkeys' detection response deteriorated
      their performance, especially in the hard task. We propose that the activity of
      microsaccades might be an efficacious indicator of the perceptual load.

PMID- 29184105
TI  - Estimating the incubation period of hand, foot and mouth disease for children in
      different age groups.
AB  - Hand, foot and mouth disease (HFMD) is a childhood disease causing large
      outbreaks frequently in Asia and occasionally in Europe and the US. The
      incubation period of HFMD was typically described as about 3-7 days but empirical
      evidence is lacking. In this study, we estimated the incubation period of HFMD
      from school outbreaks in Hong Kong, utilizing information on symptom onset and
      sick absence dates of students diagnosed with HFMD. A total of 99 HFMD cases from
      12 schools were selected for analysis. We fitted parametric models accounting for
      interval censoring. Based on the best-fitted distributions, the estimated median
      incubation periods were 4.4 (95% CI 3.8-5.1) days, 4.7 (95% CI 4.5-5.1) days and
      5.7 (95% CI 4.6-7.0) days for children in kindergartens, primary schools and
      secondary schools respectively. From the fitted distribution, the estimated
      incubation periods can be longer than 10 days for 8.8% and 23.2% of the HFMD
      cases in kindergarten and secondary schools respectively. Our results show that
      the incubation period of HFMD for secondary schools students can be longer than
      the ranges commonly described. An extended period of enhanced personal hygiene
      practice and disinfection of the environment may be needed to control outbreaks.

PMID- 29184106
TI  - Burkholderia cepacia lipase immobilized on heterofunctional magnetic
      nanoparticles and its application in biodiesel synthesis.
AB  - Biodiesel production using immobilized lipase as a biocatalyst is a promising
      process. The performance of immobilized lipase is mainly determined by supporting
      materials and immobilization method. To avoid the shortcomings of adsorption and
      covalent bonding methods, in this study, we developed a novel heterofunctional
      carrier of being strengthened anion exchange and weakened covalent binding to
      avoid activity loss and improve operational stability of the immobilized lipase.
      2,3-epoxypropyltrimethylammonium chloride with epoxy and quaternary ammonium
      group and glutaraldehyde were grafted onto aminated magnetic nanoparticles
      (AMNPs) to generate a new matrix, named GEAMNP. Then Burkholderia cepacia lipase
      (BCL) was immobilized on GEAMNP via anion exchange and covalent bonding. The
      transesterification between soybean oil and methanol was used to test the
      activities. Activity recovery of the immobilized BCL was up to 147.4% and the
      corresponding transesterification activity was 1.5-fold than that of BCL powder.
      The immobilized lipase was further used for biodiesel production to confirm its
      feasibility. The fatty acid methyl esters conversion yield could reach 96.8% in
      the first 12 h. Furthermore, the immobilized lipase, BCL-GEAMNP showed markedly
      improved operational stability, better reusability and higher esters than BCL
      GAMNP, where MNPs were only modified with (3-aminopropyl) triethoxysilane and
      glutaraldehyde.

PMID- 29184107
TI  - In-situ high-resolution visualization of laser-induced periodic nanostructures
      driven by optical feedback.
AB  - Optical feedback is often evoked in laser-induced periodic nanostructures.
      Visualizing the coupling between surfaces and light requires highly-resolved
      imaging methods. We propose in-situ structured-illumination-microscopy to observe
      ultrafast-laser-induced nanostructures during fabrication on metallic glass
      surfaces. This resolves the pulse-to-pulse development of periodic structures on
      a single irradiation site and indicates the optical feedback on surface
      topographies. Firstly, the quasi-constancy of the ripples pattern and the
      reinforcement of the surface relief with the same spatial positioning indicates a
      phase-locking mechanism that stabilizes and amplifies the ordered corrugation.
      Secondly, on sites with uncorrelated initial corrugation, we observe ripple
      patterns spatially in-phase. These feedback aspects rely on the electromagnetic
      interplay between the laser pulse and the surface relief, stabilizing the pattern
      in period and position. They are critically dependent on the space-time coherence
      of the exciting pulse. This suggests a modulation of energy according to the
      topography of the surface with a pattern phase imposed by the driving pulse. A
      scattering and interference model for ripple formation on surfaces supports the
      experimental observations. This relies on self-phase-stabilized far-field
      interaction between surface scattered wavelets and the incoming pulse front.

PMID- 29184109
TI  - Activation of Erk in ileal epithelial cells engaged in ischemic-injury repair.
AB  - Intestinal epithelial cells function as a barrier to protect our body from
      various agents; therefore, any damage to these cells must be immediately
      repaired. Several in vivo and vitro studies have shown the involvement of Erk
      (extracellular signal-regulated kinase) in the regeneration process; however, the
      spatial regulation of Erk related to tissue morphology has not been well
      documented. Using two-photon microscopy and mice carrying a Forster resonance
      energy transfer-based biosensor, we here monitored the Erk activity in the ileal
      epithelial cells of living mice. Forty-eight h after ischemia-induced injury,
      epithelial cells were observed as a monolayer covering the injured area. The Erk
      activity in these cells was higher than that in the epithelial cells at the
      surrounding crypts, and treatment with an epidermal growth factor receptor
      inhibitor cancelled the higher Erk activity. The resealing epithelial cells were
      not in the G2/M phase of the cell cycle, and Yap (Yes-associated protein) was
      localized to the nucleus. Immunostaining of intestinal ulcers from patients
      revealed ERK phosphorylation and nucleus localization of YAP without Ki-67
      staining in the resealing epithelial cells. These findings led us to propose that
      the YAP-EGFR-ERK axis is involved in migration, but not in proliferation, of the
      resealing epithelial cells.

PMID- 29184108
TI  - Acceleration of collimated 45 MeV protons by collisionless shocks driven in low
      density, large-scale gradient plasmas by a 1020 W/cm2, 1 um laser.
AB  - A new type of proton acceleration stemming from large-scale gradients, low
      density targets, irradiated by an intense near-infrared laser is observed. The
      produced protons are characterized by high-energies (with a broad spectrum), are
      emitted in a very directional manner, and the process is associated to relaxed
      laser (no need for high-contrast) and target (no need for ultra-thin or expensive
      targets) constraints. As such, this process appears quite effective compared to
      the standard and commonly used Target Normal Sheath Acceleration technique
      (TNSA), or more exploratory mechanisms like Radiation Pressure Acceleration
      (RPA). The data are underpinned by 3D numerical simulations which suggest that in
      these conditions a Low Density Collisionless Shock Acceleration (LDCSA) mechanism
      is at play, which combines an initial Collisionless Shock Acceleration (CSA) to a
      boost procured by a TNSA-like sheath field in the downward density ramp of the
      target, leading to an overall broad spectrum. Experiments performed at a laser
      intensity of 1020 W/cm2 show that LDCSA can accelerate, from ~1% critical
      density, mm-scale targets, up to 5 * 109 protons/MeV/sr/J with energies up to
      45(+/-5) MeV in a collimated (~6 degrees  half-angle) manner.

PMID- 29184110
TI  - Differential effects on membrane permeability and viability of human keratinocyte
      cells undergoing very low intensity megasonic fields.
AB  - Among different therapeutic applications of Ultrasound (US), transient membrane
      sonoporation (SP) - a temporary, non-lethal porosity, mechanically induced in
      cell membranes through US exposure - represents a compelling opportunity towards
      an efficient and safe drug delivery. Nevertheless, progresses in this field have
      been limited by an insufficient understanding of the potential cytotoxic effects
      of US related to the failure of the cellular repair and to the possible
      activation of inflammatory pathway. In this framework we studied the in vitro
      effects of very low-intensity US on a human keratinocyte cell line, which
      represents an ideal model system of skin protective barrier cells which are the
      first to be involved during medical US treatments. Bioeffects linked to US
      application at 1 MHz varying the exposure parameters were investigated by
      fluorescence microscopy and fluorescence activated cell sorting. Our results
      indicate that keratinocytes undergoing low US doses can uptake drug model
      molecules with size and efficiency which depend on exposure parameters. According
      to sub-cavitation SP models, we have identified the range of doses triggering
      transient membrane SP, actually with negligible biological damage. By increasing
      US doses we observed a reduced cells viability and an inflammatory gene
      overexpression enlightening novel healthy relevant strategies.

PMID- 29184111
TI  - Non-invasive and invasive diagnoses of aspergillosis in a rat model by mass
      spectrometry.
AB  - Invasive pulmonary aspergillosis results in 450,000 deaths per year and
      complicates cancer chemotherapy, transplantations and the treatment of other
      immunosuppressed patients. Using a rat model of experimental aspergillosis, the
      fungal siderophores ferricrocin and triacetylfusarinine C were identified as
      markers of aspergillosis and quantified in urine, serum and lung tissues.
      Biomarkers were analyzed by matrix-assisted laser desorption ionization (MALDI)
      and electrospray ionization mass spectrometry using a 12T SolariX Fourier
      transform ion cyclotron resonance (FTICR) mass spectrometer. The limits of
      detection of the ferri-forms of triacetylfusarinine C and ferricrocin in the rat
      serum were 0.28 and 0.36 ng/mL, respectively. In the rat urine the respective
      limits of detection achieved 0.02 and 0.03 ng/mL. In the sera of infected
      animals, triacetylfusarinine C was not detected but ferricrocin concentration
      fluctuated in the 3-32 ng/mL range. Notably, the mean concentrations of
      triacetylfusarinine C and ferricrocin in the rat urine were 0.37 and 0.63 MUg/mL,
      respectively. The MALDI FTICR mass spectrometry imaging illustrated the actual
      microbial ferricrocin distribution in the lung tissues and resolved the false
      positive results obtained by the light microscopy and histological staining.
      Ferricrocin and triacetylfusarinine C detection in urine represents an innovative
      non-invasive indication of Aspergillus infection in a host.

PMID- 29184112
TI  - Ecto-ADP-ribosyltransferase ARTC2.1 functionally modulates FcgammaR1 and
      FcgammaR2B on murine microglia.
AB  - Mammalian ecto-ADP-ribosyltransferases (ecto-ARTs or also ARTCs) catalyze the ADP
      ribosylation of cell surface proteins using extracellular nicotinamide adenine
      dinucleotide (NAD+) as substrate. By this post-translational protein
      modification, ecto-ARTs modulate the function of various target proteins. A
      functional role of ARTC2 has been demonstrated for peripheral immune cells such
      as T cells and macrophages. Yet, little is known about the role of ecto-ARTs in
      the central nervous system and on microglia. Here, we identified ARTC2.1 as the
      major ecto-ART expressed on murine microglia. ARTC2.1 expression was strongly
      upregulated on microglia upon co-stimulation with LPS and an ERK1/2 inhibitor or
      upon IFNbeta stimulation. We identified several target proteins modified by
      ARTC2.1 on microglia with a recently developed mass spectrometry approach,
      including two receptors for immunoglobulin G (IgG), FcgammaR1 and FcgammaR2B.
      Both proteins were verified as targets of ARTC2.1 in vitro using a radiolabeling
      assay with 32P-NAD+ as substrate. Moreover, ADP-ribosylation of both targets
      strongly inhibited their capacity to bind IgG. In concordance, ARTC2.1 induction
      in WT microglia and subsequent cell surface ADP-ribosylation significantly
      reduced the phagocytosis of IgG-coated latex beads, which was unimpaired in
      NAD+/DTT treated microglia from ARTC2.1-/- mice. Hence, induction of ARTC2.1
      expression under inflammatory conditions, and subsequent ADP-ribosylation of cell
      surface target proteins could represent a hitherto unnoticed mechanism to
      regulate the immune response of murine microglia.

PMID- 29184113
TI  - A flexible plasma-treated silver-nanowire electrode for organic light-emitting
      devices.
AB  - Silver nanowires (AgNWs) are a promising candidate to replace indium tin oxide
      (ITO) as transparent electrode material. However, the loose contact at the
      junction of the AgNWs and residual surfactant polyvinylpyrrolidone (PVP) increase
      the sheet resistance of the AgNWs. In this paper, an argon (Ar) plasma treatment
      method is applied to pristine AgNWs to remove the PVP layer and enhance the
      contact between AgNWs. By adjusting the processing time, we obtained AgNWs with a
      sheet resistance of 7.2Omega/? and a transmittance of 78% at 550 nm. To reduce
      the surface roughness of the AgNWs, a peel-off process was used to transfer the
      AgNWs to a flexible NOA63 substrate. Then, an OLED was fabricated with the plasma
      treated AgNWs electrode as anode. The highest brightness (27000 cd/m2) and
      current efficiency (11.8 cd/A) was achieved with a 30 nm thick light emitting
      layer of tris-(8-hydroxyquinoline) aluminum doped with 1% 10-(2-benzothiazolyl)
      2,3,6,7-tetrahydro-1,1,7,7-tetramethyl-1H,5 H,11H-(1)-benzopyropyrano(6,7-8
      I,j)quinolizin-11-one. Compared to thermal annealing, the plasma-treated AgNW
      film has a lower sheet resistance, a shorter processing time, and a better hole
      injection. Our results indicate that plasma treatment is an effective and
      efficient method to enhance the conductivity of AgNW films, and the plasma
      treated AgNW electrode is suitable to manufacture flexible organic optoelectronic
      devices.

PMID- 29184114
TI  - Label-free nanoscale optical metrology on myelinated axons in vivo.
AB  - In the mammalian nervous system, myelin provides electrical insulation for the
      neural circuit by forming a highly organized, multilayered thin film around the
      axon fibers. Here, we investigate the spectral reflectance from this subcellular
      nanostructure and devise a new label-free technique based on a spectroscopic
      analysis of reflected light, enabling nanoscale imaging of myelinated axons in
      their natural living state. Using this technique, we demonstrate three
      dimensional mapping of the axon diameter and sensing of dynamic changes in the
      substructure of myelin at nanoscale. We further reveal the prevalence of axon
      bulging in the brain cortex in vivo after mild compressive trauma. Our novel tool
      opens new avenues of investigation by creating unprecedented access to the
      nanostructural dynamics of live myelinated axons in health and disease.

PMID- 29184115
TI  - Scene grammar shapes the way we interact with objects, strengthens memories, and
      speeds search.
AB  - Predictions of environmental rules (here referred to as "scene grammar") can come
      in different forms: seeing a toilet in a living room would violate semantic
      predictions, while finding a toilet brush next to the toothpaste would violate
      syntactic predictions. The existence of such predictions has usually been
      investigated by showing observers images containing such grammatical violations.
      Conversely, the generative process of creating an environment according to one's
      scene grammar and its effects on behavior and memory has received little
      attention. In a virtual reality paradigm, we either instructed participants to
      arrange objects according to their scene grammar or against it. Subsequently,
      participants' memory for the arrangements was probed using a surprise recall
      (Exp1), or repeated search (Exp2) task. As a result, participants' construction
      behavior showed strategic use of larger, static objects to anchor the location of
      smaller objects which are generally the goals of everyday actions. Further
      analysis of this scene construction data revealed possible commonalities between
      the rules governing word usage in language and object usage in naturalistic
      environments. Taken together, we revealed some of the building blocks of scene
      grammar necessary for efficient behavior, which differentially influence how we
      interact with objects and what we remember about scenes.

PMID- 29184117
TI  - Context-Dependent Effect of Reverberation on Material Perception from Impact
      Sound.
AB  - Our hearing is usually robust against reverberation. This study asked how such
      robustness to daily sound is realized, and what kinds of acoustic cues contribute
      to the robustness. We focused on the perception of materials based on impact
      sounds, which is a common daily experience, and for which the responsible
      acoustic features have already been identified in the absence of reverberation.
      In our experiment, we instructed the participants to identify materials from
      impact sounds with and without reverberation. The imposition of reverberation did
      not alter the average responses across participants to perceived materials.
      However, an analysis of each participant revealed the significant effect of
      reverberation with response patterns varying among participants. The effect
      depended on the context of the stimulus presentation, namely it was smaller for a
      constant reverberation than when the reverberation varied presentation by
      presentation. The context modified the relative contribution of the spectral
      features of the sounds to material identification, while no consistent change
      across participants was observed as regards the temporal features. Although the
      detailed results varied greatly among the participants, these results suggest
      that a mechanism exists in the auditory system that compensates for reverberation
      based on adaptation to the spectral features of reverberant sound.

PMID- 29184116
TI  - Proteomic and microRNA Transcriptome Analysis revealed the microRNA-SmyD1 network
      regulation in Skeletal Muscle Fibers performance of Chinese perch.
AB  - Fish myotomes are comprised of anatomically segregated fast and slow muscle
      fibers that possess different metabolic and contractile properties. Although the
      expression profile properties in fast and slow muscle fibers had been
      investigated at the mRNA levels, a comprehensive analysis at proteomic and
      microRNA transcriptomic levels is limited. In the present study, we first
      systematically compared the proteomic and microRNA transcriptome of the slow and
      fast muscles of Chinese perch (Siniperca chuatsi). Total of 2102 proteins were
      identified in muscle tissues. Among them, 99 proteins were differentially up
      regulated and 400 were down-regulated in the fast muscle compared with slow
      muscle. MiRNA microarrays revealed that 199 miRNAs identified in the two types of
      muscle fibers. Compared with the fast muscle, the 32 miRNAs was up-regulated and
      27 down-regulated in the slow muscle. Specifically, expression of miR-103 and miR
      144 was negatively correlated with SmyD1a and SmyD1b expression in fast and slow
      muscles, respectively. The luciferase reporter assay further verified that the
      miR-103 and miR-144 directly regulated the SmyD1a and SmyD1b expression by
      targeting their 3'-UTR. The constructed miRNA-SmyD1 interaction network might
      play an important role in controlling the development and performance of
      different muscle fiber types in Chinese perch.

PMID- 29184118
TI  - CO2 Mitigation Potential of Plug-in Hybrid Electric Vehicles larger than
      expected.
AB  - The actual contribution of plug-in hybrid and battery electric vehicles (PHEV and
      BEV) to greenhouse gas mitigation depends on their real-world usage. Often BEV
      are seen as superior as they drive only electrically and do not have any direct
      emissions during driving. However, empirical evidence on which vehicle
      electrifies more mileage with a given battery capacity is lacking. Here, we
      present the first systematic overview of empirical findings on actual PHEV and
      BEV usage for the US and Germany. Contrary to common belief, PHEV with about 60
      km of real-world range currently electrify as many annual vehicles kilometres as
      BEV with a much smaller battery. Accordingly, PHEV recharged from renewable
      electricity can highly contribute to green house gas mitigation in car transport.
      Including the higher CO2eq emissions during the production phase of BEV compared
      to PHEV, PHEV show today higher CO2eq savings then BEVs compared to conventional
      vehicles. However, for significant CO2eq improvements of PHEV and particularly of
      BEVs the decarbonisation of the electricity system should go on.

PMID- 29184119
TI  - Rare earth element geochemistry characteristics of seawater and porewater from
      deep sea in western Pacific.
AB  - Deep-sea sediments contain high concentrations of rare earth element (REE) which
      have been regarded as a huge potential resource. Understanding the marine REE
      cycle is important to reveal the mechanism of REE enrichment. In order to
      determine the geochemistry characteristics and migration processes of REE,
      seawater, porewater and sediment samples were systematically collected from the
      western Pacific for REE analysis. The results show a relatively flat REE pattern
      and the HREE (Heavy REE) enrichment in surface and deep seawater respectively.
      The HREE enrichment distribution patterns, low concentrations of Mn and Fe and
      negative Ce anomaly occur in the porewater, and high Mn/Al ratios and low U
      concentrations were observed in sediment, indicating oxic condition. LREE (Light
      REE) and MREE (Middle REE) enrichment in upper layer and depletion of MREE in
      deeper layer were shown in porewater profile. This study suggests that porewater
      flux in the western Pacific basin is a minor source of REEs to seawater, and
      abundant REEs are enriched in sediments, which is mainly caused by the extensive
      oxic condition, low sedimentation rate and strong adsorption capacity of
      sediments. Hence, the removal of REEs of porewater may result in widespread REE
      rich sediments in the western Pacific basin.

PMID- 29184120
TI  - Halistanol sulfates I and J, new SIRT1-3 inhibitory steroid sulfates from a
      marine sponge of the genus Halichondria.
AB  - Two new analogs of halistanol sulfate (1) were isolated from a marine sponge
      Halichondria sp. collected at Hachijo-jima Island. Structures of these new
      halistanol sulfates I (2) and J (3) were elucidated by spectral analyses.
      Compounds 1-3 showed inhibitory activity against SIRT 1-3 with IC50 ranges of
      45.9-67.9, 18.9-21.1 and 21.8-37.5 MUM, respectively. X-ray crystallography of
      the halistanol sulfate (1) and SIRT3 complex clearly indicates that 1 binds to
      the exosite of SIRT3 that we have discovered in this study.

PMID- 29184121
TI  - Isolation and structure elucidation of lipopeptide antibiotic taromycin B from
      the activated taromycin biosynthetic gene cluster.
AB  - In the ongoing effort to unlock the chemical potential of marine bacteria,
      genetic engineering of biosynthetic gene clusters (BGCs) is increasingly used to
      awake or improve expression of biosynthetic genes that may lead to discovery of
      novel bioactive natural products. Previously, we reported the successful capture,
      engineering and heterologous expression of an orphan BGC from the marine
      actinomycete Saccharomonospora sp. CNQ-490, which resulted in the isolation of
      the novel lipopeptide antibiotic taromycin A. Herein we report the isolation and
      structure elucidation of taromycin B, the second most abundant product of the
      taromycin biosynthetic series, and show that taromycins A and B exhibit complex
      chromatographic properties indicative of interconverting conformations.
      Taromycins A and B display potent activity against methicillin-resistant
      Staphylococcus aureus and vancomycin-resistant Enterococcus faecium clinical
      isolates, suggestive that the taromycin molecular scaffold is a promising
      starting point for further derivatization to produce compounds with promising
      antibiotic characteristics.

PMID- 29184122
TI  - Bacterial alterations in salivary microbiota and their association in oral
      cancer.
AB  - Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the
      oral cavity and the fourth leading malignancy and cause of cancer-related death
      in the male population of Taiwan. Most cases are detected at advanced stages,
      resulting in poor prognosis. Therefore, improved detection of early oral health
      disorders is indispensable. The involvement of oral bacteria in inflammation and
      their association with OSCC progression provide a feasible target for diagnosis.
      Due to the nature of oral neoplasms, the diagnosis of epithelial precursor
      lesions is relatively easy compared with that of other types of cancer. However,
      the transition from an epithelial precursor lesion to cancer is slow and requires
      further and continuous follow-up. In this study, we investigated microbiota
      differences between normal individuals, epithelial precursor lesion patients, and
      cancer patients with different lifestyle habits, such as betel chewing and
      smoking, using next-generation sequencing. Overall, the oral microbiome
      compositions of five genera, Bacillus, Enterococcus, Parvimonas,
      Peptostreptococcus, and Slackia, revealed significant differences between
      epithelial precursor lesion and cancer patients and correlated with their
      classification into two clusters. These composition changes might have the
      potential to constitute a biomarker to help in monitoring the oral carcinogenesis
      transition from epithelial precursor lesion to cancer.

PMID- 29184123
TI  - Dynamic domain arrangement of CheA-CheY complex regulates bacterial thermotaxis,
      as revealed by NMR.
AB  - Bacteria utilize thermotaxis signal transduction proteins, including CheA, and
      CheY, to switch the direction of the cell movement. However, the thermally
      responsive machinery enabling warm-seeking behavior has not been identified. Here
      we examined the effects of temperature on the structure and dynamics of the full
      length CheA and CheY complex, by NMR. Our studies revealed that the CheA-CheY
      complex exists in equilibrium between multiple states, including one state that
      is preferable for the autophosphorylation of CheA, and another state that is
      preferable for the phosphotransfer from CheA to CheY. With increasing
      temperature, the equilibrium shifts toward the latter state. The temperature
      dependent population shift of the dynamic domain arrangement of the CheA-CheY
      complex induced changes in the concentrations of phosphorylated CheY that are
      comparable to those induced by chemical attractants or repellents. Therefore, the
      dynamic domain arrangement of the CheA-CheY complex functions as the primary
      thermally responsive machinery in warm-seeking behavior.

PMID- 29184124
TI  - Percolation channels: a universal idea to describe the atomic structure and
      dynamics of glasses and melts.
AB  - Understanding the links between chemical composition, nano-structure and the
      dynamic properties of silicate melts and glasses is fundamental to both Earth and
      Materials Sciences. Central to this is whether the distribution of mobile
      metallic ions is random or not. In silicate systems, such as window glass, it is
      well-established that the short-range structure is not random but metal ions
      cluster, forming percolation channels through a partly broken network of corner
      sharing SiO4 tetrahedra. In alumino-silicate glasses and melts, extensively used
      in industry and representing most of the Earth magmas, metal ions compensate the
      electrical charge deficit of AlO4- tetrahedra, but until now clustering has not
      been confirmed. Here we report how major changes in melt viscosity, together with
      glass Raman and Nuclear Magnetic Resonance measurements and Molecular Dynamics
      simulations, demonstrate that metal ions nano-segregate into percolation
      channels, making this a universal phenomenon of oxide glasses and melts.
      Furthermore, we can explain how, in both single and mixed alkali compositions,
      metal ion clustering and percolation radically affect melt mobility, central to
      understanding industrial and geological processes.

PMID- 29184125
TI  - Stiffness-dependent motility and proliferation uncoupled by deletion of CD44.
AB  - Information in the microenvironment guides complex cellular decisions such as
      whether or not to proliferate and migrate. The effects of soluble extracellular
      signals on these cellular functions are fairly well understood, but relatively
      little is known about how the extracellular matrix (ECM), and particularly the
      mechanical information in the ECM, guides these cellular decisions. Here, we show
      that CD44, a major receptor for the glycosaminoglycan ECM component hyaluronan,
      coordinates the motility and proliferative responses to ECM stiffening. We
      analyzed these cellular responses on fibronectin-coated polyacrylamide hydrogels
      prepared at a physiologic range of ECM stiffness and found that stiffening of the
      ECM leads to both cell cycling and cell motility in serum-stimulated primary
      mouse dermal fibroblasts. Remarkably, deletion of CD44 impaired stiffness
      stimulated motility of the primary cells without affecting other hallmark
      cellular responses to ECM stiffening including cell spread area, stress fiber
      formation, focal adhesion maturation, and intracellular stiffening. Even
      stiffness-mediated cell proliferation was unaffected by deletion of CD44. Our
      results reveal a novel effect of CD44, which is imposed downstream of ECM
      mechanosensing and determines if cells couple or uncouple their proliferative and
      motility responses to ECM stiffness.

PMID- 29184128
TI  - Circularly-polarized, semitransparent and double-sided holograms based on helical
      photonic structures.
AB  - Recent advances in nanofabrication techniques are opening new frontiers in
      holographic devices, with the capability to integrate various optical functions
      in a single device. However, while most efficient holograms are achieved in
      reflection-mode configurations, they are in general opaque because of the
      reflective substrate that must be used, and therefore, have limited
      applicability. Here, we present a semi-transparent, reflective computer-generated
      hologram that is circularly-polarization dependent, and reconstructs different
      wavefronts when viewed from different sides. The integrated functionality is
      realized using a single thin-film of liquid crystal with a self-organized helical
      structure that Bragg reflects circularly-polarized light over a certain band of
      wavelengths. Asymmetry depending on the viewing side is achieved by exploiting
      the limited penetration depth of light in the helical structure as well as the
      nature of liquid crystals to conform to different orientational patterns
      imprinted on the two substrates sandwiching the material. Also, because the
      operation wavelength is determined by the reflection band position, pseudo-color
      holograms can be made by simply stacking layers with different designs. The
      unique characteristics of this hologram may find applications in polarization
      encoded security holograms and see-through holographic signage where different
      information need to be displayed depending on the viewing direction.

PMID- 29184127
TI  - Deficiency of a brain-specific chemokine-like molecule, SAM3, induces cardinal
      phenotypes of autism spectrum disorders in mice.
AB  - Chemokines are small secreted signaling proteins produced by a broad range of
      cells, including immune cells. Several studies have recently suggested potential
      roles of chemokines and their receptors in the pathophysiology of autism spectrum
      disorders (ASDs). SAM3 is a novel brain-specific chemokine-like molecule with an
      unknown physiological function. We explored the relevance of chemokines in the
      development of ASD in mice, with a focus on SAM3. We generated Sam3 gene knockout
      (KO) mice and characterized their behavioral phenotypes, with a focus on those
      relevant to ASD. Sam3-deficient mice displayed all three core phenotypes of ASD:
      impaired responses to social novelty, defects in social communication, and
      increased repetitive behavior. In addition, they showed increased anxiety.
      Interestingly, gender differences were identified for several behaviors: only
      male Sam3 KO mice exhibited increased anxiety and increased repetitive behaviors.
      Sam3 KO mice did not exhibit changes in other behaviors, including locomotor
      activities, fear learning and memory, and object recognition memory. These
      findings indicate that a deficiency of SAM3, a novel brain-specific chemokine
      like molecule, may lead to the pathogenesis of ASDs and suggest the possibility
      that SAM3, a soluble factor, could be a novel therapeutic target for ASD
      treatment.

PMID- 29184126
TI  - Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell
      cycle quiescence and limits crescentic glomerulonephritis.
AB  - Crescentic rapidly progressive glomerulonephritis (RPGN) represents the most
      aggressive form of acquired glomerular disease. While most therapeutic approaches
      involve potentially toxic immunosuppressive strategies, the pathophysiology
      remains incompletely understood. Podocytes are glomerular epithelial cells that
      are normally growth-arrested because of the expression of cyclin-dependent kinase
      (CDK) inhibitors. An exception is in RPGN where podocytes undergo a deregulation
      of their differentiated phenotype and proliferate. Here we demonstrate that
      microRNA-92a (miR-92a) is enriched in podocytes of patients and mice with RPGN.
      The CDK inhibitor p57Kip2 is a major target of miR-92a that constitutively
      safeguards podocyte cell cycle quiescence. Podocyte-specific deletion of miR-92a
      in mice de-repressed the expression of p57Kip2 and prevented glomerular injury in
      RPGN. Administration of an anti-miR-92a after disease initiation prevented
      albuminuria and kidney failure, indicating miR-92a inhibition as a potential
      therapeutic strategy for RPGN. We demonstrate that miRNA induction in epithelial
      cells can break glomerular tolerance to immune injury.

PMID- 29184129
TI  - Fracture toughness and structural evolution in the TiAlN system upon annealing.
AB  - Hard coatings used to protect engineering components from external loads and
      harsh environments should ideally be strong and tough. Here we study the fracture
      toughness, K IC, of Ti1-xAlxN upon annealing by employing micro-fracture
      experiments on freestanding films. We found that K IC increases by about 11% when
      annealing the samples at 900  degrees C, because the decomposition of the
      supersaturated matrix leads to the formation of nanometer-sized domains,
      precipitation of hexagonal-structured B4 AlN (with their significantly larger
      specific volume), formation of stacking faults, and nano-twins. In contrast, for
      TiN, where no decomposition processes and formation of nanometer-sized domains
      can be initiated by an annealing treatment, the fracture toughness K IC remains
      roughly constant when annealed above the film deposition temperature. As the
      increase in K IC found for Ti1-xAlxN upon annealing is within statistical errors,
      we carried out complementary cube corner nanoindentation experiments, which
      clearly show reduced (or even impeded) crack formation for annealed Ti1-xAlxN as
      compared with their as-deposited counterpart. The ability of Ti1-xAlxN to
      maintain and even increase the fracture toughness up to high temperatures in
      combination with the concomitant age hardening effects and excellent oxidation
      resistance contributes to the success of this type of coatings.

PMID- 29184130
TI  - In-vivo longitudinal imaging of microvascular changes in irradiated oral mucosa
      of radiotherapy cancer patients using optical coherence tomography.
AB  - Mucositis is the limiting toxicity of radio(chemo)therapy of head and neck
      cancer. Diagnostics, prophylaxis and correction of this condition demand new
      accurate and objective approaches. Here we report on an in vivo longitudinal
      monitoring of the oral mucosa dynamics in 25 patients during the course of
      radiotherapy of oropharyngeal and nasopharyngeal cancer using multifunctional
      optical coherence tomography (OCT). A spectral domain OCT system with a specially
      designed oral imaging probe was used. Microvasculature visualization was based on
      temporal speckle variations of the full complex signal evaluated by high-pass
      filtering of 3D data along the slow scan axis. Angiographic image quantification
      demonstrated an increase of the vascular density and total length of capillary
      like-vessels before visual signs or clinical symptoms of mucositis occur.
      Especially significant microvascular changes compared to their initial levels
      occurred when grade two and three mucositis developed. Further, microvascular
      reaction was seen to be dose-level dependent. OCT monitoring in radiotherapy
      offers a non-invasive, convenient, label-free quantifiable structural and
      functional volumetric imaging method suitable for longitudinal human patient
      studies, furnishing fundamental radiobiological insights and potentially
      providing useful feedback data to enable adaptive radiotherapy (ART).

PMID- 29184131
TI  - Anti-cancer capacity of plasma-treated PBS: effect of chemical composition on
      cancer cell cytotoxicity.
AB  - We evaluate the anti-cancer capacity of plasma-treated PBS (pPBS), by measuring
      the concentrations of NO2- and H2O2 in pPBS, treated with a plasma jet, for
      different values of gas flow rate, gap and plasma treatment time, as well as the
      effect of pPBS on cancer cell cytotoxicity, for three different glioblastoma
      cancer cell lines, at exactly the same plasma treatment conditions. Our
      experiments reveal that pPBS is cytotoxic for all conditions investigated. A
      small variation in gap between plasma jet and liquid surface (10 mm vs 15 mm)
      significantly affects the chemical composition of pPBS and its anti-cancer
      capacity, attributed to the occurrence of discharges onto the liquid. By
      correlating the effect of gap, gas flow rate and plasma treatment time on the
      chemical composition and anti-cancer capacity of pPBS, we may conclude that H2O2
      is a more important species for the anti-cancer capacity of pPBS than NO2-. We
      also used a 0D model, developed for plasma-liquid interactions, to elucidate the
      most important mechanisms for the generation of H2O2 and NO2-. Finally, we found
      that pPBS might be more suitable for practical applications in a clinical setting
      than (commonly used) plasma-activated media (PAM), because of its higher
      stability.

PMID- 29184132
TI  - Circulating complement component 4d (C4d) correlates with tumor volume,
      chemotherapeutic response and survival in patients with malignant pleural
      mesothelioma.
AB  - Only limited information is available on the role of complement activation in
      malignant pleural mesothelioma (MPM). Thus, we investigated the circulating and
      tissue levels of the complement component 4d (C4d) in MPM. Plasma samples from 55
      MPM patients, 21 healthy volunteers (HV) and 14 patients with non-malignant
      pleural diseases (NMPD) were measured by ELISA for C4d levels. Tissue specimens
      from 32 patients were analyzed by C4d immunohistochemistry. Tumor volumetry was
      measured in 20 patients. We found no C4d labeling on tumor cells, but on ectopic
      lymphoid structures within the tumor stroma. Plasma C4d levels did not
      significantly differ between MPM, HV or NMPD. Late-stage MPM patients had higher
      plasma C4d levels compared to early-stage (p = 0.079). High circulating C4d was
      associated with a higher tumor volume (p = 0.047). Plasma C4d levels following
      induction chemotherapy were significantly higher in patients with
      stable/progressive disease compared to those with partial/major response (p =
      0.005). Strikingly, patients with low C4d levels at diagnosis had a significantly
      better overall survival, confirmed in a multivariate cox regression model (hazard
      ratio 0.263, p = 0.01). Our findings suggest that circulating plasma C4d is a
      promising new prognostic biomarker in patients with MPM and, moreover, helps to
      select patients for surgery following induction chemotherapy.

PMID- 29184133
TI  - The Neurogenic Bladder Symptom Score (NBSS): a secondary assessment of its
      validity, reliability among people with a spinal cord injury.
AB  - STUDY DESIGN: Prospective cross-sectional study. OBJECTIVES: Validate the
      Neurogenic Bladder Symptom Score (NBSS) for people with spinal cord injury (SCI).
      SETTING: United States (recruitment from community/tertiary neurourology
      clinics). METHODS: We used data from a prospective observational study of people
      with a SCI who enrolled during December 2015-September 2016. Participants
      completed the NBSS and other measurement tools (SF-12 and SCI-QOL Bladder
      Management Complications tool). Data were used to determine the internal
      consistency (Cronbach's alpha), validity (hypothesis testing), and test-re-test
      reliability (using an intraclass correlation coefficient). RESULTS: 609 people
      with a SCI had complete data. The median NBSS total score was 22 (IQR 15-30), and
      median quality of life was "mixed". The Cronbach's alpha of the total and the
      incontinence, storage/voiding, and consequences domains was 0.85, 0.93, 0.76, and
      0.49 respectively. All item to domain correlations were >=0.3, aside from 3/7 of
      the items from the consequences domain. Appropriate correlations between the NBSS
      domains and external variables and other questionnaires were observed, such as a
      moderate correlation between the SCI-QOL Bladder Management complications tool
      and the NBSS total score. For the reliability assessment, 174 people had 3 month
      followup data and did not have a significant change to their urologic health. The
      intraclass correlation coefficients were >0.75 for all subdomains and the overall
      score. CONCLUSIONS: The NBSS demonstrated good validity and reliability in a
      large cohort of people with a SCI, and is a suitable tool to assess neurogenic
      bladder symptoms. SPONSORSHIP: Patient-Centered Outcomes Research Institute
      (PCORI) Award CER14092138.

PMID- 29184135
TI  - Impact of visceral fat on surgical complications and long-term survival of
      patients with gastric cancer after radical gastrectomy.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to examine the impact of
      visceral fat on surgical complications and long-term survival for patients
      undergoing radical gastrectomy. SUBJECTS/METHODS: From 2009 to 2013, 859 patients
      who underwent curative resection for gastric cancer were enrolled from a
      prospectively maintained database. Visceral fat area (VFA) was assessed by
      preoperative CT scans. Patients were divided into two groups by VFA.
      Perioperative variables and postoperative outcomes were compared between the high
      VFA group and low VFA group. Univariable and multivariable analysis were
      performed to investigate independent risk factors of postoperative complications
      and survival. RESULTS: Some 859 patients were included in the study, 308 of whom
      were classified as high VFA. High VFA was correlated with advance age (P =
      0.020), higher albumin levels (P = 0.001), hemoglobin levels (P < 0.05), ASA
      grade (P = 0.043) and Charlson Comorbidity Index (P = 0.004). Relative to
      patients with low VFA, those with high VFA had longer surgical durations (P =
      0.004), higher rate of postoperative complications (P = 0.004), and longer
      hospital stays (P = 0.004). High VFA was identified as the only determinant for
      surgical complications by logistic regression analysis (OR, 2.236, 95% CI, 1.537
      3.254; P < 0.001). Cox proportional hazards regression revealed no correlation
      between VFA and overall survival (OS) or disease-free survival (DFS).
      CONCLUSIONS: Increased VFA independently predicts surgical complications in
      patients after gastrectomy. However, VFA is not a prognostic biomarker of OS or
      DFS in patients with gastric cancer.

PMID- 29184134
TI  - Molecular and microscopic characterization of a novel Eastern grey kangaroopox
      virus genome directly from a clinical sample.
AB  - Poxviruses are large DNA viruses with varying zoonotic potential, and are
      recognised in a broad range of wildlife. Although poxviruses have been detected
      in kangaroos, their genetic relationships to poxviruses in other animals and
      humans is not well understood. Here, we present a novel genome sequence of a
      marsupial poxvirus, the Eastern grey kangaroopox virus (EKPV-NSW), isolated from
      a wild eastern grey kangaroo. In the present study, histopathologically confirmed
      epidermal pox lesions were used to recover the full-length viral genome and
      perform electron microscopic analysis, with both immature virions and
      intracellular mature virions detected. Subsequent analysis of the EKPV-NSW genome
      demonstrated the highest degree of sequence similarity with EKPV-SC strain
      (91.51%), followed by WKPV-WA (87.93%), and MOCV1 (44.05%). The novel EKPV-NSW
      complete genome encompasses most of the chordopoxviruses protein coding genes
      (138) that are required for genome replication and expression, with only three
      essential protein coding genes being absent. The novel EKPV-NSW is missing 28
      predicted genes compared to the recently isolated EKPV-SC, and carries 21
      additional unique genes, encoding unknown proteins. Phylogenetic and
      recombination analyses showed EKPV-NSW to be the distinct available candidate
      genome of chordopoxviruses.

PMID- 29184136
TI  - Branched Pd@Rh core@shell nanocrystals with exposed Rh {100} facets: an effective
      electrocatalyst for hydrazine electro-oxidation.
AB  - Shape control of noble metal (NM) nanocrystals (NCs) is of great importance for
      improving their electrocatalytic performance. In this report, branched Pd@Rh
      core@shell NCs that have right square prism-like arms with preferential exposure
      of Rh {100} facets (denoted as b-Pd@Rh-NCs thereafter) are synthesized and
      utilized as an electrocatalyst for the hydrazine electrooxidation (HEO) in acidic
      and alkaline electrolytes. The b-Pd@Rh-NCs are obtained by the heteroepitaxial
      growth of Rh on the pre-formed branched Pd NCs (denoted as b-Pd-NCs thereafter)
      core in the presence of poly(vinyl pyrrolidone) (PVP) and bromide ions. A
      comparative analysis of the voltammetric data for the HEO shows a higher activity
      on the b-Pd@Rh-NCs exposed with Rh {100} faces than on Rh black, the b-Pd-NCs,
      and Pd black in acid and alkaline solutions, indicating a structure sensitivity
      of the reaction. Analysis of the products from the b-Pd@Rh-NCs catalysed HEO
      reveals a very high hydrazine fuel efficiency, as determined by on-line
      differential electrochemical mass spectrometry (DEMS).

PMID- 29184137
TI  - Potential ash impact from Antarctic volcanoes: Insights from Deception Island's
      most recent eruption.
AB  - Ash emitted during explosive volcanic eruptions may disperse over vast areas of
      the globe posing a threat to human health and infrastructures and causing
      significant disruption to air traffic. In Antarctica, at least five volcanoes
      have reported historic activity. However, no attention has been paid to the
      potential socio-economic and environmental consequences of an ash-forming
      eruption occurring at high southern latitudes. This work shows how ash from
      Antarctic volcanoes may pose a higher threat than previously believed. As a case
      study, we evaluate the potential impacts of ash for a given eruption scenario
      from Deception Island, one of the most active volcanoes in Antarctica. Numerical
      simulations using the novel MMB-MONARCH-ASH model demonstrate that volcanic ash
      emitted from Antarctic volcanoes could potentially encircle the globe, leading to
      significant consequences for global aviation safety. Results obtained recall the
      need for performing proper hazard assessment on Antarctic volcanoes, and are
      crucial for understanding the patterns of ash distribution at high southern
      latitudes with strong implications for tephrostratigraphy, which is pivotal to
      synchronize palaeoclimatic records.

PMID- 29184138
TI  - Centromere evolution and CpG methylation during vertebrate speciation.
AB  - Centromeres and large-scale structural variants evolve and contribute to genome
      diversity during vertebrate speciation. Here, we perform de novo long-read genome
      assembly of three inbred medaka strains that are derived from geographically
      isolated subpopulations and undergo speciation. Using single-molecule real-time
      (SMRT) sequencing, we obtain three chromosome-mapped genomes of length ~734,
      ~678, and ~744Mbp with a resource of twenty-two centromeric regions of length 20
      345kbp. Centromeres are positionally conserved among the three strains and even
      between four pairs of chromosomes that were duplicated by the teleost-specific
      whole-genome duplication 320-350 million years ago. The centromeres do not all
      evolve at a similar pace; rather, centromeric monomers in non-acrocentric
      chromosomes evolve significantly faster than those in acrocentric chromosomes.
      Using methylation sensitive SMRT reads, we uncover centromeres are mostly
      hypermethylated but have hypomethylated sub-regions that acquire unique sequence
      compositions independently. These findings reveal the potential of non
      acrocentric centromere evolution to contribute to speciation.

PMID- 29184139
TI  - Hourglass Dirac chain metal in rhenium dioxide.
AB  - Nonsymmorphic symmetries, which involve fractional lattice translations, can
      generate exotic types of fermionic excitations in crystalline materials. Here we
      propose a topological phase arising from nonsymmorphic symmetries-the hourglass
      Dirac chain metal, and predict its realization in the rhenium dioxide. We show
      that ReO2 features hourglass-type dispersion in the bulk electronic structure
      dictated by its nonsymmorphic space group. Due to time reversal and inversion
      symmetries, each band has an additional two-fold degeneracy, making the neck
      crossing-point of the hourglass four-fold degenerate. Remarkably, close to the
      Fermi level, the neck crossing-point traces out a Dirac chain-a chain of
      connected four-fold-degenerate Dirac loops-in the momentum space. The symmetry
      protection, the transformation under symmetry-breaking, and the associated
      topological surface states of the Dirac chain are revealed. Our results open the
      door to an unknown class of topological matters, and provide a platform to
      explore their intriguing physics.

PMID- 29184141
TI  - Development and growth of organs in living whole embryo and larval grafts in
      zebrafish.
AB  - Age-related systemic environments influence neurogenesis and organ regeneration
      of heterochronic parabiotic partners; however, the difficulty of manipulating
      small embryos prevents the effects of aged systemic environments on primitive
      organs at the developmental stage from being analysed. Here, we describe a novel
      transplantation system to support whole living embryos/larvae as grafts in
      immunodeficient zebrafish by the intrusion of host blood vessels into the grafts,
      allowing bodies similar to those of heterochronic parabiosis to be generated by
      subcutaneous grafting. Although grafted embryos/larvae formed most organs, not
      all organogenesis was supported equally; although the brain, eyes and the
      intestine usually developed, the liver, testes and heart developed insufficiently
      or even occasionally disappeared. Removal of host germ cells stimulated testis
      development in grafted embryos. These results indicate that primitive testes are
      susceptible to the systemic environments that originated from the germ cells of
      aged hosts and imply that the primitive liver and heart are similar. Upon
      applying this method to embryonic lethal mutants, various types of organs,
      including testes that developed in germ-cell-removed recipients, and viable
      offspring were obtained from the mutants. This unique transplantation system will
      lead to new insights into the age-related systemic environments that are crucial
      for organogenesis in vertebrates.

PMID- 29184140
TI  - Induced cortical tension restores functional junctions in adhesion-defective
      carcinoma cells.
AB  - Normal epithelial cells are stably connected to each other via the apical
      junctional complex (AJC). AJCs, however, tend to be disrupted during tumor
      progression, and this process is implicated in cancer dissemination. Here, using
      colon carcinoma cells that fail to form AJCs, we investigated molecular defects
      behind this failure through a search for chemical compounds that could restore
      AJCs, and found that microtubule-polymerization inhibitors (MTIs) were effective.
      MTIs activated GEF-H1/RhoA signaling, causing actomyosin contraction at the
      apical cortex. This contraction transmitted force to the cadherin-catenin
      complex, resulting in a mechanosensitive recruitment of vinculin to cell
      junctions. This process, in turn, recruited PDZ-RhoGEF to the junctions, leading
      to the RhoA/ROCK/LIM kinase/cofilin-dependent stabilization of the junctions.
      RhoGAP depletion mimicked these MTI-mediated processes. Cells that normally
      organize AJCs did not show such MTI/RhoA sensitivity. Thus, advanced carcinoma
      cells require elevated RhoA activity for establishing robust junctions, which
      triggers tension-sensitive reorganization of actin/adhesion regulators.

PMID- 29184143
TI  - Corrigendum: High-rate aluminium yolk-shell nanoparticle anode for Li-ion battery
      with long cycle life and ultrahigh capacity.
AB  - This corrects the article DOI: 10.1038/ncomms8872.

PMID- 29184142
TI  - A simulation model of neuroprogenitor proliferation dynamics predicts age-related
      loss of hippocampal neurogenesis but not astrogenesis.
AB  - Adult hippocampal neuroprogenitors give rise to both neurons and astrocytes. As
      neuroprogenitors are lost with increased age, neurogenesis concomitantly
      decreases. However, the dynamics of neuron and astrocyte generation throughout
      adulthood has not been systematically examined. Here, we analyzed the hippocampal
      niche both longitudinally (from 2 h to 30d of cell life) and transversally (from
      1 m to 12 m of age) and generated a Marsaglia polar random simulation model to
      predict newborn cell dynamics. The sharp decrease in newborn neuron production
      throughout adulthood was largely predicted by the number of proliferating
      neuroprogenitors at each age. In contrast, newborn astrocyte decay was slower and
      associated with their increased yield in mature mice. As a result, the niche
      shifted from neurogenic to neuro/astrogenic with increased age. Our data provide
      a simple "end-point" model to understand the hippocampal niche changes across
      adulthood and suggest yet unexplored functions of newborn astrocytes for the
      aging hippocampal circuitry.

PMID- 29184144
TI  - Sex differences in peripheral not central immune responses to pain-inducing
      injury.
AB  - Women suffer chronic pain more frequently than men. It is not clear whether this
      is due to differences in higher level cognitive processes or basic nociceptive
      responses. In this study we used a mouse model of neuropathic pain to dissociate
      these factors. We performed RNA-seq on purified peripheral afferent neurons, but
      found no striking differences in gene expression between male and female mice,
      neither before nor after nerve injury. Similarly, spinal cord immune responses
      between the sexes appeared to be indistinguishable when studied by flow cytometry
      or qRT-PCR. Differences emerged only upon studying peripheral immune cell
      infiltration into the dorsal root ganglion, suggesting that adaptive immune
      responses in neuropathic pain could be sexually dimorphic.

PMID- 29184145
TI  - Erratum: Modulation of mRNA and lncRNA expression dynamics by the Set2-Rpd3S
      pathway.
AB  - This corrects the article DOI: 10.1038/ncomms13534.

PMID- 29184146
TI  - 2,3,4',5-tetrahydroxystilbene-2-O-beta-D-glucoside exacerbates acetaminophen
      induced hepatotoxicity by inducing hepatic expression of CYP2E1, CYP3A4 and
      CYP1A2.
AB  - Hepatotoxicity induced by medicinal herb Polygonum multiflorum Thunb. attracts
      wide attention in the world recently. 2,3,4',5-tetrahydroxystilbene-2-O-beta-D
      glucoside (TSG) is a main active compound in Polygonum multiflorum Thunb. This
      study aims to observe TSG-provided the aggravation on acetaminophen (APAP)
      induced hepatotoxicity in mice by inducing hepatic expression of cytochrome P450
      (CYP450) enzymes. Serum alanine/aspartate aminotransferase (ALT/AST) analysis and
      liver histological evaluation showed that TSG (200, 400, 800 mg/kg) exacerbated
      the hepatotoxicity induced by sub-toxic dose of APAP (200 mg/kg) in mice, but TSG
      alone had no hepatotoxicity. TSG aggravated hepatic reduced glutathione (GSH)
      depletion and APAP-cysteine adducts (APAP-CYS) formation induced by APAP in mice.
      TSG increased the expression of CYP2E1, CYP3A4 and CYP1A2 both in mice and in
      human normal liver L-02 hepatocytes. TSG also enhanced liver catalytic activity
      of CYP2E1, CYP3A4 and CYP1A2 in mice. TSG induced the nuclear translocation of
      aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR), and TSG-provided
      the aggravation on APAP-induced hepatotoxicity in mice was reversed by PXR or AHR
      inhibitors. In summary, our results demonstrate that TSG enhances hepatic
      expression of CYP3A4, CYP2E1 and CYP1A2, and thus exacerbates the hepatotoxicity
      induced by APAP in mice. PXR and AHR both play some important roles in this
      process.

PMID- 29184147
TI  - The origin of prostate gland-secreted IgA and IgG.
AB  - The prostate secretes immunoglobulin (Ig) A (IgA) and IgG; however, how
      immunoglobulins reach the secretion, where the plasma cells are located, whether
      immunoglobulins are antigen-specific and where activation of the adaptive
      response occurs are still unknown. Immune cells, including CD45RA+ cells, were
      scattered in the stroma and not organized mucosae-associated lymphoid-tissue. IgA
      (but not IgG) immunostaining identified stromal plasma cells and epithelial cells
      in non-immunized rats. Injected tetramethylrhodamine-IgA transcytosed the
      epithelium along with polymeric immunoglobulin receptor. Oral immunization with
      ovalbumin/mesopourous SBA-15 silica adjuvant resulted in more stromal
      CD45RA+/IgA+ cells, increased content of ovalbumin-specific IgA and IgG, and the
      appearance of intraepithelial CD45RA+/IgG+ cells. An increased number of
      dendritic cells that cooperate in other sites with transient immunocompetent
      lymphocytes, and the higher levels of interleukin-1beta, interferon-gamma and
      transforming growth factor-beta, explain the levels of specific antibodies. Nasal
      immunization produced similar results except for the increase in dendritic cells.
      This immunomodulatory strategy seems useful to boost immunity against
      genitourinary infections and, perhaps, cancer.

PMID- 29184148
TI  - Evaluation of radionuclides and decay simulation in a terrestrial environment for
      health risk assessment.
AB  - This study is to assess the natural radioactivity level in soil samples in
      communities bordering the Tano Basin in Ghana. The radioactivity concentration of
      238U, 232Th and 40K have been determined using gamma-ray spectrometry, moreover,
      the absorbed dose rates and annual effective dose were calculated. MATLAB R2013
      script was written to simulate the decay of the radionuclides 238U, 232Th and 40K
      using their respective half-lives. This is to determine the future impact of
      natural radionuclides and estimate future anthropogenic inputs. The level 238U,
      232Th, and 40K ranged from (1.60 to 21.3), (2.78 to 32.2) and (111 to 528) with
      average values of be 8.65 Bqkg-1, 12.5 Bqkg-1 and 214 Bqkg-1 respectively in
      soil. The activity concentrations were lower than United Nations Scientific
      Committee on the Effects of Atomic Radiation guidelines for 238U, 232Th and 40K.
      The absorbed dose rates and annual effective dose were found to be in range of
      7.79 to 37.8 nGy h-1 and 9.56E + 00 to 4.64E + 01 uSvy-1 respectively. The
      overall annual effective dose was lower than the allowable limit of 1mSvy-1 set
      by International Commission on Radiological Protection. Hex, Hin and excess
      lifetime cancer risk (ELCR) were calculated and found to be within
      internationally recommended values.

PMID- 29184149
TI  - Corrigendum: Potent single-domain antibodies that arrest respiratory syncytial
      virus fusion protein in its prefusion state.
AB  - This corrects the article DOI: 10.1038/ncomms14158.

PMID- 29184150
TI  - Control of the interaction strength of photonic molecules by nanometer precise 3D
      fabrication.
AB  - Applications for high resolution 3D profiles, so-called grayscale lithography,
      exist in diverse fields such as optics, nanofluidics and tribology. All of them
      require the fabrication of patterns with reliable absolute patterning depth
      independent of the substrate location and target materials. Here we present a
      complete patterning and pattern-transfer solution based on thermal scanning probe
      lithography (t-SPL) and dry etching. We demonstrate the fabrication of 3D
      profiles in silicon and silicon oxide with nanometer scale accuracy of absolute
      depth levels. An accuracy of less than 1nm standard deviation in t-SPL is
      achieved by providing an accurate physical model of the writing process to a
      model-based implementation of a closed-loop lithography process. For transfering
      the pattern to a target substrate we optimized the etch process and demonstrate
      linear amplification of grayscale patterns into silicon and silicon oxide with
      amplification ratios of ~6 and ~1, respectively. The performance of the entire
      process is demonstrated by manufacturing photonic molecules of desired
      interaction strength. Excellent agreement of fabricated and simulated structures
      has been achieved.

PMID- 29184151
TI  - Association between antibodies against group B Streptococcus surface proteins and
      recto-vaginal colonisation during pregnancy.
AB  - Group B Streptococcus (GBS) recto-vaginal colonisation in pregnant women is the
      major risk factor for early-onset invasive GBS disease in their newborns. We
      aimed to determine the association between serum antibody levels against 11 GBS
      surface proteins and recto-vaginal acquisition of GBS colonisation during
      pregnancy. Sera collected from pregnant women at 20-25 weeks and >=37 weeks of
      gestation age were measured for IgG titres against GBS surface proteins using  a
      multiplex immunoassay. Women were evaluated for recto-vaginal colonisation every
      4-5 weeks. We observed that the likelihood of becoming colonised with GBS during
      pregnancy was lower in women with IgG titres >=200 U/mL against gbs0233 (adjusted
      OR = 0.47 [95% CI: 0.25-0.89], p = 0.021) and >=85 U/mL for gbs1539 (adjusted OR
      = 0.44 [95% CI: 0.24-0.82], p = 0.01) when comparing between women who acquired
      GBS colonisation and those that remained free of GBS colonisation throughout
      pregnancy. IgG titres (U/mL) specific to BibA and Sip were higher in pregnant
      women colonised with GBS (380.19 and 223.87, respectively) compared to women with
      negative GBS cultures (234.42 and 186.21, respectively; p < 0.01) at >=37 weeks
      gestation. Antibodies induced by gbs0233 and gbs1539 were associated with a
      reduced likelihood of recto-vaginal GBS acquisition during pregnancy and warrant
      further investigation as vaccine targets.

PMID- 29184152
TI  - Pressure driven spin transition in siderite and magnesiosiderite single crystals.
AB  - Iron-bearing carbonates are candidate phases for carbon storage in the deep Earth
      and may play an important role for the Earth's carbon cycle. To elucidate the
      properties of carbonates at conditions of the deep Earth, we investigated the
      pressure driven magnetic high spin to low spin transition of synthetic siderite
      FeCO3 and magnesiosiderite (Mg0.74Fe0.26)CO3 single crystals for pressures up to
      57 GPa using diamond anvil cells and x-ray Raman scattering spectroscopy to
      directly probe the iron 3d electron configuration. An extremely sharp transition
      for siderite single crystal occurs at a notably low pressure of 40.4 +/- 0.1 GPa
      with a transition width of 0.7 GPa when using the very soft pressure medium
      helium. In contrast, we observe a broadening of the transition width to 4.4 GPa
      for siderite with a surprising additional shift of the transition pressure to
      44.3 +/- 0.4 GPa when argon is used as pressure medium. The difference is
      assigned to larger pressure gradients in case of argon. For magnesiosiderite
      loaded with argon, the transition occurs at 44.8 +/- 0.8 GPa showing similar
      width as siderite. Hence, no compositional effect on the spin transition pressure
      is observed. The spectra measured within the spin crossover regime indicate
      coexistence of regions of pure high- and low-spin configuration within the single
      crystal.

PMID- 29184153
TI  - Severe illness caused by Rickettsia sibirica subspecies sibirica BJ-90 infection,
      China.

PMID- 29184154
TI  - A leptospiral AAA+ chaperone-Ntn peptidase complex, HslUV, contributes to the
      intracellular survival of Leptospira interrogans in hosts and the transmission of
      leptospirosis.
AB  - Leptospirosis caused by Leptospira is a zoonotic disease of global importance but
      it is considered as an emerging or re-emerging infectious disease in many areas
      in the world. Until now, the mechanisms about pathogenesis and transmission of
      Leptospira remains poorly understood. As eukaryotic and prokaryotic proteins can
      be denatured in adverse environments and chaperone-protease/peptidase complexes
      degrade these harmful proteins, we speculate that infection may also cause
      leptospiral protein denaturation, and the HslU and HslV proteins of L.
      interrogans may compose a complex to degrade denatured proteins that enhances
      leptospiral survival in hosts. Here we show that leptospiral HslUV is an ATP
      dependent chaperone-peptidase complex containing ATPase associated with various
      cellular activity (AAA+) and N-terminal nucleophile (Ntn) hydrolase superfamily
      domains, respectively, which hydrolyzed casein and chymotrypsin-like substrates,
      and this hydrolysis was blocked by threonine protease inhibitors. The infection
      of J774A.1 macrophages caused the increase of leptospiral denatured protein
      aggresomes, but more aggresomes accumulated in hslUV gene-deleted mutant. The
      abundant denatured leptospiral proteins are involved in ribosomal structure,
      flagellar assembly, two-component signaling systems and transmembrane transport.
      Compared to the wild-type strain, infection of cells in vitro with the mutant
      resulted in a higher number of dead leptospires, less leptospiral colony-forming
      units and lower growth ability, but also displayed a lower half lethal dose,
      attenuated histopathological injury and decreased leptospiral loading in lungs,
      liver, kidneys, peripheral blood and urine in hamsters. Therefore, our findings
      confirmed that HslUV AAA+ chaperone-Ntn peptidase complex of L. interrogans
      contributes to leptospiral survival in hosts and transmission of leptospirosis.

PMID- 29184155
TI  - Isolation and molecular characterization of prevalent Fowl adenovirus strains in
      southwestern China during 2015-2016 for the development of a control strategy.
AB  - Fowl adenovirus (FAdV) has caused significant losses in chicken flocks throughout
      China in recent years. However, the current understanding of the genetic and
      pathogenic characteristics of the FAdV epidemic in southwestern China remains
      poorly understood. In this study, a total of 22 strains were isolated from liver
      samples of diseased chickens from farms in southwestern China. Phylogenetic
      analysis based on the hexon loop-1 gene showed that the 22 isolates were
      clustered into four distinct serotypes: FAdV serotype 4 (FAdV-4) (86.4%, 19/22),
      FAdV-2 (4.5%, 1/22), FAdV-8a (4.5%, 1/22), and FAdV-8b (4.5%, 1/22). FAdV-4 was
      the predominant serotype in southwestern China. Pathogenicity testing showed that
      the FAdV-4 serotype strain CH/GZXF/1602 and FAdV-8a strain CH/CQBS/1504 were
      pathogenic to chickens, with mortality rates reaching as high as 80% and 20%,
      respectively. The primary clinical feature observed following infection with
      strain CH/GZXF/1602 (FAdV-4) was hepatitis-hydropericardium syndrome, and that of
      strain CH/CQBS/1504 (FAdV-8a) was inclusion body hepatitis. Conversely, the FAdV
      2 serotype strain CH/GZXF/1511 and FAdV-8b serotype strain CH/CQBS/1512 was not
      observed to be pathogenic in chickens. Then, CH/GZXF/1602 (FAdV-4) was selected
      for the preparation of an inactivated oil-emulsion vaccine. Immune studies on
      Partridge Shank broilers showed that a single dose immunization at 17 days of age
      could not only protect against homologous challenge with virulent FAdV-4 but also
      provided protection against clinical disease following challenge with the
      heterologous FAdV-8b virulent strain until 70 days of age. The characterization
      of newly prevalent FAdV strains provides a valuable reference for the development
      of an efficacious control strategy.

PMID- 29184156
TI  - HIV-1 Env DNA prime plus gp120 and gp70-V1V2 boosts induce high level of V1V2
      specific IgG and ADCC responses and low level of Env-specific IgA response:
      implication for improving RV144 vaccine regimen.

PMID- 29184157
TI  - Genetic evolution of influenza H9N2 viruses isolated from various hosts in China
      from 1994 to 2013.
AB  - Influenza H9N2 subtype viruses and their reassortants (such as H7N9) are posing
      increasing threats to birds and humans in China. During 2009-2013, multiple novel
      subtype viruses with H9N2 original genes emerged in China. Yet, the genetic
      evolution of H9N2 viruses in various host organisms in China has not been
      systematically investigated since 2009. In the present study, we performed large
      scale sequence analysis of H9N2 viral genomes from public databases, representing
      the spectrum of viruses isolated from birds, mammals and humans in China from
      1994 to 2013, and updated the clade classification for each segment. We
      identified 117 distinct genotypes in 730 H9N2 viruses. We analyzed the sequences
      of all eight segments in each virus and found three important time points: the
      years 2000, 2006 and 2010. In the periods divided by these years, genotypic
      diversity, geographic distribution and host range changed considerably. Genotypic
      diversity fluctuated greatly in 2000 and 2006. Since 2010, a single genotype
      became predominant in poultry throughout China, and the eastern coastal region
      became the newly identified epidemic center. Throughout their 20-year prevalence
      in China, H9N2 influenza viruses have emerged and adapted from aquatic birds to
      chickens. The minor avian species and wild birds exacerbated H9N2 genotypes by
      providing diversified genes, and chickens were the most prevalent vector in which
      the viruses evolved and expanded their prevalence. It is the necessity for
      surveillance and disease control on live-bird markets, poultry farms and wild
      bird habitats in China.

PMID- 29184158
TI  - Meteorological factors affect the epidemiology of hemorrhagic fever with renal
      syndrome via altering the breeding and hantavirus-carrying states of rodents and
      mites: a 9 years' longitudinal study.
AB  - The incidence of hemorrhagic fever with renal syndrome (HFRS) in Qingdao, China
      was three times higher than that of the average national level. Here we
      characterized the epidemiology, ecological determinants and pathogen evolution of
      HFRS in Qingdao during 2007-2015. In this longitudinal study, a total of 1846
      HFRS patients and 41 HFRS-related deaths were reported. HFRS in Qingdao peaked
      once a year in the fourth quarter. We built a time series generalized additive
      model, and found that meteorological factors in the previous quarter could
      accurately predict HFRS occurrence. To explore how meteorological factors
      influenced the epidemic of HFRS, we analyzed the relationship between
      meteorological factors and hantavirus-carrying states of the hosts (including
      rodents and shrews). Comprehensive analysis showed humidity was correlated to
      high host densities in the third quarter and high hantavirus-carrying rates of
      animal hosts in the third to fourth quarters, which might contribute to HFRS peak
      in the fourth quarter. We further compared the L segments of hantaviruses from
      HFRS patients, animal hosts and ectoparasites. Phylogenetic analysis showed that
      hantaviruses in gamasid and trombiculid mites were the same as those from the
      hosts. This indicated mites also contributed to the transmission of hantavirus.
      Furthermore, Hantaan virus from HFRS patients, hosts and mites in Qingdao formed
      a distinct phylogenetic cluster. A new clade of Seoul virus was also identified
      in the hosts. Overall, meteorological factors increase HFRS incidence possibly
      via facilitating hosts' reproduction and consequent mite-mediated hantavirus
      transmission. New hantavirus subtypes evolved in Qingdao represent new challenges
      of fighting against HFRS.

PMID- 29184159
TI  - Cell-free protein synthesis from non-growing, stressed Escherichia coli.
AB  - Cell-free protein synthesis is a versatile protein production system. Performance
      of the protein synthesis depends on highly active cytoplasmic extracts. Extracts
      from E. coli are believed to work best; they are routinely obtained from
      exponential growing cells, aiming to capture the most active translation system.
      Here, we report an active cell-free protein synthesis system derived from cells
      harvested at non-growth, stressed conditions. We found a downshift of ribosomes
      and proteins. However, a characterization revealed that the stoichiometry of
      ribosomes and key translation factors was conserved, pointing to a fully intact
      translation system. This was emphasized by synthesis rates, which were comparable
      to those of systems obtained from fast-growing cells. Our approach is less
      laborious than traditional extract preparation methods and multiplies the yield
      of extract per cultivation. This simplified growth protocol has the potential to
      attract new entrants to cell-free protein synthesis and to broaden the pool of
      applications. In this respect, a translation system originating from heat
      stressed, non-growing E. coli enabled an extension of endogenous transcription
      units. This was demonstrated by the sigma factor depending activation of parallel
      transcription. Our cell-free expression platform adds to the existing versatility
      of cell-free translation systems and presents a tool for cell-free biology.

PMID- 29184160
TI  - Fabrication-Method-Dependent Excited State Dynamics in CH3NH3PbI3 Perovskite
      Films.
AB  - Understanding the excited-state dynamics in perovskite photovoltaics is necessary
      for progress in these materials, but changes in dynamics depending on the
      fabrication processes used for perovskite photoactive layers remain poorly
      characterised. Here we report a comparative study on femtosecond transient
      absorption (TA) in CH3NH3PbI3 perovskite films fabricated by various solution
      processing methods. The grain sizes and the number of voids between grains on
      each film varied according to the film synthesis method. At the low excitation
      fluence of 0.37 MUJ cm-2, fast signal drops in TA dyanmics within 1.5 ps were
      observed in all perovskite films, but the signal drop magnitudes differed becuase
      of the variations in charge migration to trap states and band gap
      renormalisation. For high excitation fluences, the buil-up time of the TA signal
      was increased by the activated hot-phonon bottleneck, while the signal decay rate
      was accelerated by fluence-dependent high-order charge recombination. These
      fluence-dependent dynamics changed for different perovskite fabrication methords,
      indicating that the dynamics were affected by morphological features such as
      grain sizes and defects.

PMID- 29184161
TI  - Multiple-stressor effects in an apex predator: combined influence of pollutants
      and sea ice decline on lipid metabolism in polar bears.
AB  - There is growing evidence from experimental and human epidemiological studies
      that many pollutants can disrupt lipid metabolism. In Arctic wildlife, the
      occurrence of such compounds could have serious consequences for seasonal
      feeders. We set out to study whether organohalogenated compounds (OHCs) could
      cause disruption of energy metabolism in female polar bears (Ursus maritimus)
      from Svalbard, Norway (n = 112). We analyzed biomarkers of energy metabolism
      including the abundance profiles of nine lipid-related genes, fatty acid (FA)
      synthesis and elongation indices in adipose tissue, and concentrations of lipid
      related variables in plasma (cholesterol, high-density lipoprotein,
      triglycerides). Furthermore, the plasma metabolome and lipidome were
      characterized by low molecular weight metabolites and lipid fingerprinting,
      respectively. Polychlorinated biphenyls, chlordanes, brominated diphenyl ethers
      and perfluoroalkyl substances were significantly related to biomarkers involved
      in lipid accumulation, FA metabolism, insulin utilization, and cholesterol
      homeostasis. Moreover, the effects of pollutants were measurable at the
      metabolome and lipidome levels. Our results indicate that several OHCs affect
      lipid biosynthesis and catabolism in female polar bears. Furthermore, these
      effects were more pronounced when combined with reduced sea ice extent and
      thickness, suggesting that climate-driven sea ice decline and OHCs have
      synergistic negative effects on polar bears.

PMID- 29184162
TI  - Dacarbazine nanoparticle topical delivery system for the treatment of melanoma.
AB  - Dacarbazine (DZ) is poorly soluble in water with the short half-life in blood
      circulation, low rate of response with the toxic effect which ultimately limits
      its utilization of the treatment of skin cancer. In view of this background
      current study was designed for development of dacarbazine laden nanoparticle
      (DZNP) and dacarbazine laden nanocream (DZNC) topical delivery system for the
      treatment of melanoma. Firstly DZNP was prepared. By using DZNP its cream
      formulation prepared for topic drug delivery for melanoma. Dacarbazine
      nanoparticle and its cream were evaluated for morphology, drug load capacity,
      efficiency of nanoencapsulation and size of particle and zeta potential,
      Transmission Electron Microscopy (TEM), determination of pH, spreadability and
      viscosity, in vitro drug release capacity and its cytotoxic potential. The
      particle size of DZNP and DZNC was 16.3 +/- 8.1 nm and 16.9 +/- 7.8 nm
      respectively. pH value and spreadability of nanoparticle cream were found to be
      6.7 +/- 0.14 g cm/sec and 55.23 +/- 3.13 g cm/sec respectively. Nanoencapsulation
      efficiency and Drug loading capacity were 67.4 +/- 3.5% and 6.73 mg/10 mg
      respectively. IC50 of dacarbazine nanoparticle was 0.19 mg/ml while it was 0.63
      mg/ml for nanoparticle cream. It can be concluded that DZNP and its cream can be
      effectively used as a topical formulation for the treatment of melanoma.

PMID- 29184163
TI  - All-trans retinoic acid enhances cytotoxicity of CIK cells against human lung
      adenocarcinoma by upregulating MICA and IL-2 secretion.
AB  - To determine the growth inhibition capability of all-trans retinoic acid (ATRA)
      with cytokine-induced killer cells (CIKs), we evaluated their effects, alone and
      in combination, on human lung carcinoma A549 cells. CIKs treated with ATRA
      significantly inhibited cell growth. Additionally, CIK with ATRA synergistically
      inhibited migration and invasiveness, colony formation of A549 and NCI-H520
      cells. Furthermore, analysis of apoptosis markers Bcl-2, Bax, Survivin and
      cleaved Caspase-3 showed that Bcl-2 and Survivin mRNA levels significantly
      decreased, and that Bax mRNA significantly increased, in the CIK + ATRA-treated
      cells, with corresponding effects on their respective proteins. The involved
      mechanisms may be associated with upregulated expression of MHC class I-Related
      Chain (MICA) and interleukin (IL)-2. These results suggest that administration of
      combined CIK and ATRA is a potentially novel treatment for lung carcinoma.

PMID- 29184164
TI  - Correlates of compliance with recommended levels of physical activity in
      children.
AB  - The purpose of this study was to describe children's daily compliance with
      moderate-to-vigorous physical activity (MVPA) recommendations across a week in
      different parts of the world, and to identify individual- and school-level
      correlates that may explain differences in daily MVPA compliance. The sample
      included 6553 children aged 9-11 years from 12 countries, and multilevel
      statistical analyses were used, including both child- and school-level variables.
      Most children did not comply with the MVPA guidelines on a daily basis: Chinese
      children complied the least, whereas Finnish, Australian, Colombian, UK, and
      Kenyan children complied the most. Boys (rate ratio [RR] = 1.47) and children
      with higher unhealthy diet scores (RR = 1.08) complied more, but overweight/obese
      children (RR = 0.81), earlier maturing children (RR = 0.93), and those who spent
      more time in screen activities (RR = 0.98) and sleeping (RR = 0.96) had the
      lowest compliance. At the school level, children with access to playground or
      sport equipment (RR = 0.88, for both) tended to comply less, whereas those with
      access to a gymnasium outside the school hours complied more with the MVPA
      guidelines (RR = 1.14). Significant between-country differences in children's
      daily MVPA compliance were observed, reflecting not only site characteristics,
      but also the importance of individual traits and local school contexts.

PMID- 29184165
TI  - ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of
      auditory synaptopathy.
AB  - The etiologies and prevalence of sporadic, postlingual-onset, progressive
      auditory neuropathy spectrum disorder (ANSD) have rarely been documented. Thus,
      we aimed to evaluate the prevalence and molecular etiologies of these cases.
      Three out of 106 sporadic progressive hearing losses turned out to manifest ANSD.
      Through whole exome sequencing and subsequent bioinformatics analysis, two out of
      the three were found to share a de novo variant, p.E818K of ATP1A3, which had
      been reported to cause exclusively CAPOS (cerebellar ataxia, areflexia, pes
      cavus, optic atrophy, and sensorineural hearing loss) syndrome. However, hearing
      loss induced by CAPOS has never been characterized to date. Interestingly, the
      first proband did not manifest any features of CAPOS, except subclinical
      areflexia; however, the phenotypes of second proband was compatible with that of
      CAPOS, making this the first reported CAPOS allele in Koreans. This ANSD
      phenotype was compatible with known expression of ATP1A3 mainly in the synapse
      between afferent nerve and inner hair cells. Based on this, cochlear implantation
      (CI) was performed in the first proband, leading to remarkable benefits.
      Collectively, the de novo ATP1A3 variant can cause postlingual-onset auditory
      synaptopathy, making this gene a significant contributor to sporadic progressive
      ANSD and a biomarker ensuring favorable short-term CI outcomes.

PMID- 29184166
TI  - Quantitative, in situ analysis of mRNAs and proteins with subcellular resolution.
AB  - We describe here a method, termed immunoFISH, for simultaneous in situ analysis
      of the composition and distribution of proteins and individual RNA transcripts in
      single cells. Individual RNA molecules are labeled by hybridization and target
      proteins are concurrently stained using immunofluorescence. Multicolor
      fluorescence images are acquired and analyzed to determine the abundance,
      composition, and distribution of hybridized probes and immunofluorescence. We
      assessed the ability of immunoFISH to simultaneous quantify protein and
      transcript levels and distribution in cultured HER2 positive breast cancer cells
      and human breast tumor samples. We demonstrated the utility of this assay in
      several applications including demonstration of the existence of a layer of
      normal myoepithelial KRT14 expressing cells that separate HER2+ cancer cells from
      the stromal and immune microenvironment in HER2+ invasive breast cancer. Our
      studies show that immunoFISH provides quantitative information about the spatial
      heterogeneity in transcriptional and proteomic features that exist between and
      within cells.

PMID- 29184167
TI  - Effect of nebivolol or atenolol vs. placebo on cardiovascular health in subjects
      with borderline blood pressure: the EVIDENCE study.
AB  - Pharmacotherapy to protect the arteries may be appropriate for individuals with
      high-normal blood pressure who are at risk for future cardiovascular disease
      (CVD). Nebivolol (NEB) in contrast to atenolol (ATE) may have a beneficial effect
      on endothelial function and may be more effective than ATE in preventing CVD.
      Sixty subjects with preHTN or borderline BP and abnormal small artery elasticity
      (SAE) underwent evaluation with 10 tests, including large and small artery
      elasticity, resting and treadmill exercise BP, carotid intimal-media thickness,
      retinal vascular photography, micro-albuminuria, electrocardiography,
      echocardiography, and plasma B-type natriuretic peptide level. Each test scored
      as normal (0), borderline (1), or abnormal (2), and the total disease score (DS)
      was calculated by adding the test scores. Subjects were randomized double-blind
      to placebo (PLAC, n = 22), NEB 5/10 mg/day (n = 20), or ATE 25/50 mg/day (n = 18)
      once daily for 9 months. After 9 months, in the group receiving NEB the mean
      (standard deviation) DS decreased from baseline 4.3 (2.6) to 2.8 (2.4) (P <
      0.007), with ATE from 5.4 (2.5) to 3.5 (1.9) (P = 0.0006), and with PLAC from 5.2
      (3.0) to 4.5 (2.6) (P = 0.18). SAE increased in the NEB group from 6.0 (2.2) to
      8.4 (3.4) ml/mmHg * 100 (P = 0.0001), whereas there was no significant change in
      the ATE and PLAC groups. Thus, nebivolol improves small artery function more than
      atenolol in asymptomatic subjects with preHTN or borderline BP, despite their
      similar BP-lowering effect.

PMID- 29184168
TI  - Mucopolysaccharidosis at play?

PMID- 29184169
TI  - NMNAT1 variants cause cone and cone-rod dystrophy.
AB  - Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal
      diseases that predominantly affect the cone photoreceptors. The underlying
      disease gene is not known in approximately 75% of autosomal recessive cases.
      Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber
      congenital amaurosis (LCA). We report two patients where clinical phenotyping
      indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified,
      with Case 1 showing an extremely rare homozygous variant c.[271G > A]
      p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A]
      p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the
      observation of an associated macular atrophy phenotype, indicated that these
      variants were disease-causing. This report demonstrates that the variants in
      NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic
      investigations of the patients with CD or CRD should include NMNAT1 in the genes
      examined.

PMID- 29184170
TI  - 19p13 microduplications encompassing NFIX are responsible for intellectual
      disability, short stature and small head circumference.
AB  - Syndromes caused by copy number variations are described as reciprocal when they
      result from deletions or duplications of the same chromosomal region. When
      comparing the phenotypes of these syndromes, various clinical features could be
      described as reversed, probably due to the opposite effect of these imbalances on
      the expression of genes located at this locus. The NFIX gene codes for a
      transcription factor implicated in neurogenesis and chondrocyte differentiation.
      Microdeletions and loss of function variants of NFIX are responsible for Sotos
      syndrome-2 (also described as Malan syndrome), a syndromic form of intellectual
      disability associated with overgrowth and macrocephaly. Here, we report a cohort
      of nine patients harboring microduplications encompassing NFIX. These patients
      exhibit variable intellectual disability, short stature and small head
      circumference, which can be described as a reversed Sotos syndrome-2 phenotype.
      Strikingly, such a reversed phenotype has already been described in patients
      harboring microduplications encompassing NSD1, the gene whose deletions and loss
      of-function variants are responsible for classical Sotos syndrome. Even though
      the type/contre-type concept has been criticized, this model seems to give a
      plausible explanation for the pathogenicity of 19p13 microduplications, and the
      common phenotype observed in our cohort.

PMID- 29184171
TI  - Points to consider for laboratories reporting results from diagnostic genomic
      sequencing.
AB  - Although NGS technologies are well-embedded in the clinical setting for
      identification of genetic causes of disease, guidelines issued by professional
      bodies are inconsistent regarding some aspects of reporting results. Most
      recommendations do not give detailed guidance about whether variants of uncertain
      significance (VUS) should be reported by laboratory personnel to clinicians, and
      give conflicting messages regarding whether unsolicited findings (UF) should be
      reported. There are also differences both in their recommendations regarding
      whether actively searching for secondary findings (SF) is appropriate, and in the
      extent to which they address the duty (or lack thereof) to reanalyse variants
      when new information arises. An interdisciplinary working group considered the
      current guidelines, their own experiences, and data from a recent qualitative
      study to develop a set of points to consider for laboratories reporting results
      from diagnostic NGS. These points to consider fall under six categories: (i)
      Testing approaches and technologies used, (ii) Approaches for VUS; (iii)
      Approaches for reporting UF, (iv) Approaches regarding SF; (v) Reanalysis of data
      & re-contact; and vi) Minors. While it is unclear whether uniformity in reporting
      across all laboratories is desirable, we hope these points to consider will be
      useful to diagnostic laboratories as they develop their processes for making
      decisions about reporting VUS and UF from NGS in the diagnostic context.

PMID- 29184172
TI  - Capturing endosomal vesicles at the Golgi.
AB  - Membrane trafficking specificity between distinct compartments ensures that cargo
      proteins and lipids are delivered to their target organelle. However, accurate
      recognition of cargo carriers by tethering factors on target membranes is poorly
      understood. TBC1D23 is now identified as an adaptor that links endosome-derived
      vesicles with golgins at the trans-Golgi.

PMID- 29184173
TI  - Erratum: DNA sensing in senescence.
AB  - This corrects the article DOI: 10.1038/ncb3603.

PMID- 29184174
TI  - Erratum: PKM2 methylation by CARM1 activates aerobic glycolysis to promote
      tumorigenesis.
AB  - This corrects the article DOI: 10.1038/ncb3630.

PMID- 29184175
TI  - Erratum: EGFR signalling controls cellular fate and pancreatic organogenesis by
      regulating apicobasal polarity.
AB  - This corrects the article DOI: 10.1038/ncb3628.

PMID- 29184176
TI  - Addendum: A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour
      progression.
AB  - This corrects the article DOI: 10.1038/ncb3595.

PMID- 29184177
TI  - Corrigendum: Cholesterol and fatty acids regulate cysteine ubiquitylation of
      ACAT2 through competitive oxidation.
AB  - This corrects the article DOI: 10.1038/ncb3551.

PMID- 29184178
TI  - Of stem cells and ethics.

PMID- 29184179
TI  - F-actin organizes the nucleus.
AB  - After mitosis, the nucleus must be rebuilt and chromatin decondensed to permit
      interphase genomic functions, but decondensation mechanisms are poorly
      understood. Now, the traditional cytoskeletal protein actin is shown to form
      transient nuclear filaments that are required for chromatin decondensation and
      nuclear expansion at mitotic exit.

PMID- 29184180
TI  - RNA takes over control of DNA break repair.
AB  - Small RNAs generated at DNA break sites are implicated in mammalian DNA repair.
      Now, a study shows that following the formation of DNA double-strand breaks,
      bidirectional transcription events adjacent to the break generate small RNAs that
      trigger the DNA damage response by local RNA:RNA interactions.

PMID- 29184181
TI  - Corrigendum: Insufficient antibody validation challenges oestrogen receptor beta
      research.
AB  - This corrects the article DOI: 10.1038/ncomms15840.

PMID- 29184182
TI  - A quantitative method for microstructural analysis of myelinated axons in the
      injured rodent brain.
AB  - MRI studies (e.g. using diffusion tensor imaging) revealed that injury to white
      matter tracts, as observed in for instance perinatal white matter injury and
      multiple sclerosis, leads to compromised microstructure of myelinated axonal
      tracts. Alterations in white matter microstructure are also present in a wide
      range of neurological disorders including autism-spectrum disorders,
      schizophrenia and ADHD. Whereas currently myelin quantity measures are often used
      in translational animal models of white matter disease, it can be an important
      valuable addition to study the microstructural organization of myelination
      patterns in greater detail. Here, we describe methods to extensively study the
      microstructure of cortical myelination by immunostaining for myelin. To validate
      these methods, we carefully analyzed the organization of myelinated axons running
      from the external capsule towards the outer layers of the cortex in three rodent
      models of neonatal brain injury and in an adult stroke model, that have all been
      associated with myelination impairments. This unique, relatively easy and
      sensitive methodology can be applied to study subtle differences in myelination
      patterns in animal models in which aberrations in myelination integrity are
      suspected. Importantly, the described methods can be applied to determine
      efficacy of novel experimental treatments on microstructural organization of
      cortical myelination.

PMID- 29184184
TI  - The devotion to surrogate outcomes in drug development for liver disease.

PMID- 29184183
TI  - Optogenetic and chemogenetic techniques for neurogastroenterology.
AB  - Optogenetics and chemogenetics comprise a wide variety of applications in which
      genetically encoded actuators and indicators are used to modulate and monitor
      activity with high cellular specificity. Over the past 10 years, development of
      these genetically encoded tools has contributed tremendously to our understanding
      of integrated physiology. In concert with the continued refinement of probes,
      strategies to target transgene expression to specific cell types have also made
      much progress in the past 20 years. In addition, the successful implementation of
      optogenetic and chemogenetic techniques thrives thanks to ongoing advances in
      live imaging microscopy and optical technology. Although innovation of
      optogenetic and chemogenetic methods has been primarily driven by researchers
      studying the central nervous system, these techniques also hold great promise to
      boost research in neurogastroenterology. In this Review, we describe the
      different classes of tools that are currently available and give an overview of
      the strategies to target them to specific cell types in the gut wall. We discuss
      the possibilities and limitations of optogenetic and chemogenetic technology in
      the gut and provide an overview of their current use, with a focus on the enteric
      nervous system. Furthermore, we suggest some experiments that can advance our
      understanding of how the intrinsic and extrinsic neural networks of the gut
      control gastrointestinal function.

PMID- 29184186
TI  - Oesophagus: A new candidate for the progenitor cell of Barrett metaplasia.

PMID- 29184187
TI  - Liver: Delineating the role of angiogenesis in liver fibrosis.

PMID- 29184185
TI  - Cellular senescence in gastrointestinal diseases: from pathogenesis to
      therapeutics.
AB  - Senescence is a durable cell cycle arrest that can be induced in response to
      various stress factors, such as telomere erosion, DNA damage or the aberrant
      activation of oncogenes. In addition to its well-established role as a stress
      response programme, research has revealed important physiological roles of
      senescence in nondisease settings, such as embryonic development, wound healing,
      tissue repair and ageing. Senescent cells secrete various cytokines, chemokines,
      matrix remodelling proteases and growth factors, a phenotype collectively
      referred to as the senescence-associated secretory phenotype. These factors evoke
      immune responses that, depending on the pathophysiological context, can either
      prevent or even fuel disease and tumorigenesis. Remarkably, even the gut
      microbiota can influence senescence in various organs. In this Review, we provide
      an introduction to cellular senescence, addressed particularly to
      gastroenterologists and hepatologists, and discuss the implications of senescence
      for the pathogenesis of malignant and nonmalignant gastrointestinal and
      hepatobiliary diseases. We conclude with an outlook on how modulation of cellular
      senescence might be used for therapeutic purposes.

PMID- 29184189
TI  - Ultra-short pulse propagation model for multi-core fibers based on local modes.
AB  - Multi-core fibers (MCFs) have sparked a new paradigm in optical communications
      and open new possibilities and applications in experimental physics and other
      fields of science, such as biological and medical imaging. In many of these
      cases, ultra-short pulse propagation is revealed as a key factor that enables us
      to exploit the full potential of this technology. Unfortunately, the propagation
      of such pulses in real MCFs has not yet been modelled considering polarization
      effects or typical random medium perturbations, which usually give rise to both
      longitudinal and temporal birefringent effects. Using the concept of local modes,
      we develop here an accurate ultra-short pulse propagation model that rigorously
      accounts for these phenomena in single-mode MCFs. Based on this theory, we
      demonstrate analytically and numerically the intermodal dispersion between
      different LP01 polarized core modes induced by these random perturbations when
      propagating femtosecond pulses in the linear and nonlinear fiber regimes. The
      ever-decreasing core-to-core distance significantly enhances the intermodal
      dispersion induced by these birefringent effects, which can become the major
      physical impairment in the single-mode regime. To demonstrate the power of our
      model, we give explicit strategies to reduce the impact of this optical
      impairment by increasing the MCF perturbations.

PMID- 29184188
TI  - A Novel Communication Value Task Demonstrates Evidence of Response Bias in Cases
      with Presbyacusis.
AB  - Decision-making about the expected value of an experience or behavior can explain
      hearing health behaviors in older adults with hearing loss. Forty-four middle
      aged to older adults (68.45 +/- 7.73 years) performed a task in which they were
      asked to decide whether information from a surgeon or an administrative assistant
      would be important to their health in hypothetical communication scenarios across
      visual signal-to-noise ratios (SNR). Participants also could choose to view the
      briefly presented sentences multiple times. The number of these effortful
      attempts to read the stimuli served as a measure of demand for information to
      make a health importance decision. Participants with poorer high frequency
      hearing more frequently decided that information was important to their health
      compared to participants with better high frequency hearing. This appeared to
      reflect a response bias because participants with high frequency hearing loss
      demonstrated shorter response latencies when they rated the sentences as
      important to their health. However, elevated high frequency hearing thresholds
      did not predict demand for information to make a health importance decision. The
      results highlight the utility of a performance-based measure to characterize
      effort and expected value from performing tasks in older adults with hearing
      loss.

PMID- 29184191
TI  - A micro-Raman study of exfoliated few-layered n-type Bi2 Te2.7Se0.3.
AB  - Previously we showed that the thermoelectric (TE) performance of bulk n-type
      Bi2Te2.7Se0.3 can be enhanced by subjecting it to a combined process of chemical
      or mechanical exfoliation (C/ME) followed by a rapid densification and restacking
      of the exfoliated layers via the spark-plasma-sintering technique (SPS). Here, we
      present a systematic micro-Raman study of two-dimensional flakes of n-type
      Bi2Te2.7Se0.3 produced by the C/ME process, as a function of the flake thickness.
      We found Raman evidence for flakes with: (i) integer number of quintuples which
      exhibited a strong electron-phonon coupling, and (ii) non-integer number of
      quintuples, or sub-quintuples which exhibited the forbidden IR active mode due to
      symmetry lowering. Detailed atomic force microscopy was used to confirm the
      number of quintuples in all flakes examined in this study. The restacking and
      densification of these flakes by SPS promoted the formation of charged grain
      boundaries, which led to the enhanced TE properties via the energy filtering
      process.

PMID- 29184190
TI  - Bacterial endosymbionts influence host sexuality and reveal reproductive genes of
      early divergent fungi.
AB  - Many heritable mutualisms, in which beneficial symbionts are transmitted
      vertically between host generations, originate as antagonisms with parasite
      dispersal constrained by the host. Only after the parasite gains control over its
      transmission is the symbiosis expected to transition from antagonism to
      mutualism. Here, we explore this prediction in the mutualism between the fungus
      Rhizopus microsporus (Rm, Mucoromycotina) and a beta-proteobacterium
      Burkholderia, which controls host asexual reproduction. We show that reproductive
      addiction of Rm to endobacteria extends to mating, and is mediated by the
      symbiont gaining transcriptional control of the fungal ras2 gene, which encodes a
      GTPase central to fungal reproductive development. We also discover candidate G
      protein-coupled receptors for the perception of trisporic acids, mating
      pheromones unique to Mucoromycotina. Our results demonstrate that regulating host
      asexual proliferation and modifying its sexual reproduction are sufficient for
      the symbiont's control of its own transmission, needed for antagonism-to
      mutualism transition in heritable symbioses. These properties establish the Rm
      Burkholderia symbiosis as a powerful system for identifying reproductive genes in
      Mucoromycotina.

PMID- 29184192
TI  - Robust generation of entangled state via ground-state antiblockade of Rydberg
      atoms.
AB  - We propose a mechanism of ground-state antiblockade of Rydberg atoms, which is
      then exploited to prepare two-atom entangled state via three different kinds of
      pulses. First we use the pulses in the form of sin2 and cos2 functions and obtain
      a maximally entangled state at an accurate interaction time. Then the method of
      stimulated Raman adiabatic passage (STIRAP) is adopted for the entanglement
      generation, which is immune to the fluctuations of revelent parameters but
      requires a long time. Finally we capitalize the advantages of the former two
      methods and employ shortcuts to adiabatic passage (STAP) to generate the maximal
      entanglement. The strictly numerical simulation reveals that the current scheme
      is robust against spontaneous emission of atoms due to the virtual excitation of
      Rydberg states, and all of the above methods favor a high fidelity with the
      present experimental technology.

PMID- 29184193
TI  - Proof of concept for a passive sampler for monitoring of gaseous elemental
      mercury in artisanal gold mining.
AB  - Mercury emissions from artisanal gold mining operations occurring in roughly 80
      developing countries are a major workplace health hazard for millions of people
      as well as the largest contributor to global mercury pollution. There are no
      portable, cheap, and rapid methods able to inform workers or health practitioners
      of mercury exposure on site in remote locations. In this work, a proof of concept
      for a miniaturized mercury sampler, prepared by the direct reduction of gold into
      the porous nanostructures of Vycor glass (PVG), is introduced. Mercury retention
      on the PVG/Au sampler induces significant color changes, due to the formation of
      Au-Hg amalgam that affects the surface plasmon resonance characteristics of the
      material. The color change can potentially be quantified by the analysis of
      pictures obtained with a cell phone camera rapidly and onsite. Laboratory
      experiments showed the viability of using PVG/Au as passive sampler for
      monitoring of Hg degrees . PVG/Au samplers were then deployed in an artisanal and
      small-scale gold mining (ASGM) operations in Burkina Faso and it was able to
      indicate personal mercury exposures. The amount of mercury quantified in the
      samplers for all miners was higher than the current personal exposure limit set
      by the US Occupational Safety & Health Administration (OSHA).

PMID- 29184194
TI  - Interventions for management of post-stroke depression: A Bayesian network meta
      analysis of 23 randomized controlled trials.
AB  - Post-stroke depression (PSD) is an important complication of stroke, leading to
      increased disability and mortality. Given that there is no consensus on which
      treatment is optimal for PSD, we aimed to evaluate the relative efficacies of
      available pharmacological and non-pharmacological interventions. We conducted a
      network meta-analysis to incorporate evidence from relevant trials and provide
      direct and indirect comparisons. We searched PubMed, Cochrane Library Central
      Register of Controlled Trials, and Embase until November 1, 2016 for randomized
      controlled trials involving different pharmacological and non-pharmacological PSD
      treatment interventions. The primary outcome was reduction in the Hamilton
      depression scale (HAMD) score. This study is registered with PROSPERO (number,
      CRD42016049049). Of a total of 1,152 studies, 23 randomized trials comprising
      1,542 participants were included. Nine PSD treatment interventions were
      considered. Noradrenaline reuptake inhibitor (NRI) was associated with the
      highest reduction in the HAMD score, followed by tricyclic antidepressant (TCA),
      psychotherapy plus antidepressant, and selective serotonin reuptake inhibitor
      (SSRI). This study indicated that NRIs, SSRIs, and TCAs are associated with a
      considerable higher HAMD score reduction compared with the control treatment.
      rTMS is a beneficial therapeutic approach for managing PSD to obtain good
      response to treatments compared with the control treatment.

PMID- 29184196
TI  - Stem cells: Regenerating the skin of a young patient.

PMID- 29184197
TI  - Mixed selectivity morphs population codes in prefrontal cortex.
AB  - The prefrontal cortex maintains working memory information in the presence of
      distracting stimuli. It has long been thought that sustained activity in
      individual neurons or groups of neurons was responsible for maintaining
      information in the form of a persistent, stable code. Here we show that, upon the
      presentation of a distractor, information in the lateral prefrontal cortex was
      reorganized into a different pattern of activity to create a morphed stable code
      without losing information. In contrast, the code in the frontal eye fields
      persisted across different delay periods but exhibited substantial instability
      and information loss after the presentation of a distractor. We found that
      neurons with mixed-selective responses were necessary and sufficient for the
      morphing of code and that these neurons were more abundant in the lateral
      prefrontal cortex than the frontal eye fields. This suggests that mixed
      selectivity provides populations with code-morphing capability, a property that
      may underlie cognitive flexibility.

PMID- 29184195
TI  - Chromatin dependencies in cancer and inflammation.
AB  - Multiple cell-signalling pathways converge on chromatin to induce gene expression
      programmes. The inducible transcriptional programmes that are established as a
      result of inflammatory or oncogenic signals are controlled by shared chromatin
      regulators. Therapeutic targeting of such chromatin dependencies has proved
      effective for controlling tumorigenesis and for preventing immunopathologies that
      are driven by overt inflammation. In this Review, we discuss how chromatin
      dependencies are established to regulate the expression of key oncogenes and
      inflammation-promoting genes and how a better mechanistic understanding of such
      chromatin dependencies can be leveraged to improve the magnitude, timing,
      duration and selectivity of cell responses with the aim of minimizing unwanted
      cellular and systemic effects. Recently, exciting progress has been made in
      cancer immunotherapy and in the development of drugs that target chromatin
      regulators. We discuss recent advances in clinical trials and the challenge of
      combining immune-cell-based therapies and epigenetic therapies to improve human
      health.

PMID- 29184198
TI  - Activation of planarian TRPA1 by reactive oxygen species reveals a conserved
      mechanism for animal nociception.
AB  - All animals must detect noxious stimuli to initiate protective behavior, but the
      evolutionary origin of nociceptive systems is not well understood. Here we show
      that noxious heat and irritant chemicals elicit robust escape behaviors in the
      planarian Schmidtea mediterranea and that the conserved ion channel TRPA1 is
      required for these responses. TRPA1-mutant Drosophila flies are also defective in
      noxious-heat responses. We find that either planarian or human TRPA1 can restore
      noxious-heat avoidance to TRPA1-mutant Drosophila, although neither is directly
      activated by heat. Instead, our data suggest that TRPA1 activation is mediated by
      H2O2 and reactive oxygen species, early markers of tissue damage rapidly produced
      as a result of heat exposure. Together, our data reveal a core function for TRPA1
      in noxious heat transduction, demonstrate its conservation from planarians to
      humans, and imply that animal nociceptive systems may share a common ancestry,
      tracing back to a progenitor that lived more than 500 million years ago.

PMID- 29184199
TI  - Thalamic inhibition regulates critical-period plasticity in visual cortex and
      thalamus.
AB  - During critical periods of development, experience shapes cortical circuits,
      resulting in the acquisition of functions used throughout life. The classic
      example of critical-period plasticity is ocular dominance (OD) plasticity, which
      optimizes binocular vision but can reduce the responsiveness of the primary
      visual cortex (V1) to an eye providing low-grade visual input. The onset of the
      critical period of OD plasticity involves the maturation of inhibitory synapses
      within V1, specifically those containing the GABAA receptor alpha1 subunit. Here
      we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus
      (dLGN) also undergo OD plasticity. This process depends on thalamic alpha1
      containing synapses and is required for consolidation of the OD shift in V1
      during long-term deprivation. Our findings demonstrate that thalamic inhibitory
      circuits play a central role in the regulation of the critical period. This has
      far-reaching consequences for the interpretation of studies investigating the
      molecular and cellular mechanisms regulating critical periods of brain
      development.

PMID- 29184200
TI  - Altered cerebellar connectivity in autism and cerebellar-mediated rescue of
      autism-related behaviors in mice.
AB  - Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently
      reported in autism spectrum disorders (ASD). Although RCrusI is functionally
      connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to
      ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans
      resulted in altered functional connectivity with the inferior parietal lobule,
      and children with ASD showed atypical functional connectivity in this circuit.
      Atypical RCrusI-inferior parietal lobule structural connectivity was also evident
      in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically
      mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD
      related social, repetitive, and restricted behaviors, while stimulation of RCrusI
      PNs rescued social impairment in the PN TscI ASD mouse model. Together, these
      studies reveal important roles for RCrusI in ASD-related behaviors. Further, the
      rescue of social behaviors in an ASD mouse model suggests that investigation of
      the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

PMID- 29184201
TI  - Elucidating the underlying components of food valuation in the human
      orbitofrontal cortex.
AB  - The valuation of food is a fundamental component of our decision-making. Yet
      little is known about how value signals for food and other rewards are
      constructed by the brain. Using a food-based decision task in human participants,
      we found that subjective values can be predicted from beliefs about constituent
      nutritive attributes of food: protein, fat, carbohydrates and vitamin content.
      Multivariate analyses of functional MRI data demonstrated that, while food value
      is represented in patterns of neural activity in both medial and lateral parts of
      the orbitofrontal cortex (OFC), only the lateral OFC represents the elemental
      nutritive attributes. Effective connectivity analyses further indicate that
      information about the nutritive attributes represented in the lateral OFC is
      integrated within the medial OFC to compute an overall value. These findings
      provide a mechanistic account for the construction of food value from its
      constituent nutrients.

PMID- 29184202
TI  - The central amygdala controls learning in the lateral amygdala.
AB  - Experience-driven synaptic plasticity in the lateral amygdala is thought to
      underlie the formation of associations between sensory stimuli and an ensuing
      threat. However, how the central amygdala participates in such a learning process
      remains unclear. Here we show that PKC-delta-expressing central amygdala neurons
      are essential for the synaptic plasticity underlying learning in the lateral
      amygdala, as they convey information about the unconditioned stimulus to lateral
      amygdala neurons during fear conditioning.

PMID- 29184203
TI  - Arid1b haploinsufficiency disrupts cortical interneuron development and mouse
      behavior.
AB  - Haploinsufficiency of the AT-rich interactive domain 1B (ARID1B) gene causes
      autism spectrum disorder and intellectual disability; however, the
      neurobiological basis for this is unknown. Here we generated Arid1b-knockout mice
      and examined heterozygotes to model human patients. Arid1b-heterozygous mice
      showed a decreased number of cortical GABAergic interneurons and reduced
      proliferation of interneuron progenitors in the ganglionic eminence. Arid1b
      haploinsufficiency also led to an imbalance between excitatory and inhibitory
      synapses in the cerebral cortex. Furthermore, we found that Arid1b
      haploinsufficiency suppressed histone H3 lysine 9 acetylation (H3K9ac) overall
      and particularly reduced H3K9ac of the Pvalb promoter, resulting in decreased
      transcription. Arid1b-heterozygous mice exhibited abnormal cognitive and social
      behaviors, which were rescued by treatment with a positive allosteric GABAA
      receptor modulator. Our results demonstrate a critical role for Arid1b in
      interneuron development and behavior and provide insight into the pathogenesis of
      autism spectrum disorder and intellectual disability.

PMID- 29184205
TI  - An opening for humor in melancholy.

PMID- 29184204
TI  - Weak correlations between hemodynamic signals and ongoing neural activity during
      the resting state.
AB  - Spontaneous fluctuations in hemodynamic signals in the absence of a task or overt
      stimulation are used to infer neural activity. We tested this coupling by
      simultaneously measuring neural activity and changes in cerebral blood volume
      (CBV) in the somatosensory cortex of awake, head-fixed mice during periods of
      true rest and during whisker stimulation and volitional whisking. We found that
      neurovascular coupling was similar across states and that large, spontaneous CBV
      changes in the absence of sensory input were driven by volitional whisker and
      body movements. Hemodynamic signals during periods of rest were weakly correlated
      with neural activity. Spontaneous fluctuations in CBV and vessel diameter
      persisted when local neural spiking and glutamatergic input were blocked, as well
      as during blockade of noradrenergic receptors, suggesting a non-neuronal origin
      for spontaneous CBV fluctuations. Spontaneous hemodynamic signals reflect a
      combination of behavior, local neural activity, and putatively non-neural
      processes.

PMID- 29184206
TI  - A multiregional proteomic survey of the postnatal human brain.
AB  - Detailed observations of transcriptional, translational and post-translational
      events in the human brain are essential to improving our understanding of its
      development, function and vulnerability to disease. Here, we exploited label-free
      quantitative tandem mass-spectrometry to create an in-depth proteomic survey of
      regions of the postnatal human brain, ranging in age from early infancy to
      adulthood. Integration of protein data with existing matched whole-transcriptome
      sequencing (RNA-seq) from the BrainSpan project revealed varied patterns of
      protein-RNA relationships, with generally increased magnitudes of protein
      abundance differences between brain regions compared to RNA. Many of the
      differences amplified in protein data were reflective of cytoarchitectural and
      functional variation between brain regions. Comparing structurally similar
      cortical regions revealed significant differences in the abundances of receptor
      associated and resident plasma membrane proteins that were not readily observed
      in the RNA expression data.

PMID- 29184207
TI  - Lateral geniculate neurons projecting to primary visual cortex show ocular
      dominance plasticity in adult mice.
AB  - Experience-dependent plasticity in the mature visual system is widely considered
      to be cortical. Using chronic two-photon Ca2+ imaging of thalamic afferents in
      layer 1 of binocular visual cortex, we provide evidence against this tenet: the
      respective dorsal lateral geniculate nucleus (dLGN) cells showed pronounced
      ocular dominance (OD) shifts after monocular deprivation in adult mice. Most
      (86%), but not all, of dLGN cell boutons were monocular during normal visual
      experience. Following deprivation, initially deprived-eye-dominated boutons
      reduced or lost their visual responsiveness to that eye and frequently became
      responsive to the non-deprived eye. This cannot be explained by eye-specific
      cortical changes propagating to dLGN via cortico-thalamic feedback because the
      shift in dLGN responses was largely resistant to cortical inactivation using the
      GABAA receptor agonist muscimol. Our data suggest that OD shifts observed in the
      binocular visual cortex of adult mice may at least partially reflect plasticity
      of eye-specific inputs onto dLGN neurons.

PMID- 29184208
TI  - Temporally precise single-cell-resolution optogenetics.
AB  - Optogenetic control of individual neurons with high temporal precision within
      intact mammalian brain circuitry would enable powerful explorations of how neural
      circuits operate. Two-photon computer-generated holography enables precise
      sculpting of light and could in principle enable simultaneous illumination of
      many neurons in a network, with the requisite temporal precision to simulate
      accurate neural codes. We designed a high-efficacy soma-targeted opsin, finding
      that fusing the N-terminal 150 residues of kainate receptor subunit 2 (KA2) to
      the recently discovered high-photocurrent channelrhodopsin CoChR restricted
      expression of this opsin primarily to the cell body of mammalian cortical
      neurons. In combination with two-photon holographic stimulation, we found that
      this somatic CoChR (soCoChR) enabled photostimulation of individual cells in
      mouse cortical brain slices with single-cell resolution and <1-ms temporal
      precision. We used soCoChR to perform connectivity mapping on intact cortical
      circuits.

PMID- 29184210
TI  - Thalamic functions in distributed cognitive control.
AB  - Cognition can be conceptualized as a set of algorithmic control functions whose
      real-time deployment determines how an organism stores and uses information to
      guide thought and action. A subset of these functions is required for goal
      directed selection and amplification of sensory signals-broadly referred to as
      attention-and for its flexible control and its interaction with processes such as
      working memory and decision making. While the contribution of recurrent cortical
      microcircuits to cognition has been extensively studied, the role of the thalamus
      is just beginning to be elucidated. Here we highlight recent studies across
      rodents and primates showing how thalamus contributes to attentional control. In
      addition to high-fidelity information relay to or between cortical regions,
      thalamic circuits shift and sustain functional interactions within and across
      cortical areas. This thalamic process enables rapid coordination of spatially
      segregated cortical computations, thereby constructing task-relevant functional
      networks. Because such function may be critical for cognitive flexibility,
      clarifying its mechanisms will likely expand our basic understanding of cognitive
      control and its perturbation in disease.

PMID- 29184209
TI  - A craniofacial-specific monosynaptic circuit enables heightened affective pain.
AB  - Humans often rank craniofacial pain as more severe than body pain. Evidence
      suggests that a stimulus of the same intensity induces stronger pain in the face
      than in the body. However, the underlying neural circuitry for the differential
      processing of facial versus bodily pain remains unknown. Interestingly, the
      lateral parabrachial nucleus (PBL), a critical node in the affective pain
      circuit, is activated more strongly by noxious stimulation of the face than of
      the hindpaw. Using a novel activity-dependent technology called CANE developed in
      our laboratory, we identified and selectively labeled noxious-stimulus-activated
      PBL neurons and performed comprehensive anatomical input-output mapping.
      Surprisingly, we uncovered a hitherto uncharacterized monosynaptic connection
      between cranial sensory neurons and the PBL-nociceptive neurons. Optogenetic
      activation of this monosynaptic craniofacial-to-PBL projection induced robust
      escape and avoidance behaviors and stress calls, whereas optogenetic silencing
      specifically reduced facial nociception. The monosynaptic circuit revealed here
      provides a neural substrate for heightened craniofacial affective pain.

PMID- 29184211
TI  - Whole genome sequencing in psychiatric disorders: the WGSPD consortium.

PMID- 29184213
TI  - The underdog pathway gets a boost.

PMID- 29184212
TI  - Oxytocin-receptor-expressing neurons in the parabrachial nucleus regulate fluid
      intake.
AB  - Brain regions that regulate fluid satiation are not well characterized, yet are
      essential for understanding fluid homeostasis. We found that oxytocin-receptor
      expressing neurons in the parabrachial nucleus of mice (OxtrPBN neurons) are key
      regulators of fluid satiation. Chemogenetic activation of OxtrPBN neurons
      robustly suppressed noncaloric fluid intake, but did not decrease food intake
      after fasting or salt intake following salt depletion; inactivation increased
      saline intake after dehydration and hypertonic saline injection. Under
      physiological conditions, OxtrPBN neurons were activated by fluid satiation and
      hypertonic saline injection. OxtrPBN neurons were directly innervated by oxytocin
      neurons in the paraventricular hypothalamus (OxtPVH neurons), which mildly
      attenuated fluid intake. Activation of neurons in the nucleus of the solitary
      tract substantially suppressed fluid intake and activated OxtrPBN neurons. Our
      results suggest that OxtrPBN neurons act as a key node in the fluid satiation
      neurocircuitry, which acts to decrease water and/or saline intake to prevent or
      attenuate hypervolemia and hypernatremia.

PMID- 29184214
TI  - Breaking down a meal.

PMID- 29184216
TI  - Graphene oxide enhances the specificity of the polymerase chain reaction by
      modifying primer-template matching.
AB  - Aiming at improved specificity, nanoparticle assisted polymerase chain reaction
      (PCR) has been widely studied and shown to improve PCR. However, the reliability
      and mechanism of this method are still controversial. Here, we demonstrated that
      1 MUg/mL of graphene oxide (GO) effectively enhances the specificity of the error
      prone multi-round PCR. Mismatched primers were designed as interference to
      produce nonspecific products when the same amounts of matched and mismatched
      primers were added into semi-multiplex PCR. It was found that GO can enhance
      specificity by suppressing the amplification of mismatched primers. We monitored
      the primer-template-polymerase-GO interactions involved in the PCR using a
      capillary electrophoresis/laser-induced fluorescence polarization (CE-LIFP)
      assay. The results showed that the addition of GO promoted the formation of a
      matched primer-template complex, but suppressed the formation of a mismatched
      primer-template complex during PCR, suggesting that interactions between the
      primers and GO play an essential role. Furthermore, we successfully amplified the
      FOXL2 gene from PEGFP-N1 vectors using GO to eliminate the nonspecific products
      in PCR. Taken together, these results suggest that the GO can be used as an
      efficient additive for improving the conventional PCR system.

PMID- 29184215
TI  - Social stress induces neurovascular pathology promoting depression.
AB  - Studies suggest that heightened peripheral inflammation contributes to the
      pathogenesis of major depressive disorder. We investigated the effect of chronic
      social defeat stress, a mouse model of depression, on blood-brain barrier (BBB)
      permeability and infiltration of peripheral immune signals. We found reduced
      expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and
      abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible
      but not resilient mice. CLDN5 expression was also decreased in NAc of depressed
      patients. Cldn5 downregulation was sufficient to induce depression-like behaviors
      following subthreshold social stress whereas chronic antidepressant treatment
      rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of
      stress-susceptible or mice injected with adeno-associated virus expressing shRNA
      against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6)
      into brain parenchyma and subsequent expression of depression-like behaviors.
      These findings suggest that chronic social stress alters BBB integrity through
      loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across
      the BBB and depression.

PMID- 29184217
TI  - Increased sensibility to acute acoustic and blast trauma among patients with
      acoustic neuroma.
AB  - The article shows 2 cases of unusual presentation of acute acoustic trauma and
      blast injury due to occupational exposure. In the case of both patients the range
      of impaired frequencies in pure tone audiograms was atypical for this kind of
      causative factor. Both patients had symmetrical hearing before the accident
      (which was confirmed by provided results of hearing controls during their
      employment). A history of noise/blast exposure, the onset of symptoms directly
      after harmful exposure, symmetrical hearing before the trauma documented with
      audiograms, directed initial diagnosis towards acoustic/blast trauma, however, of
      atypical course. Acute acoustic and blast trauma and coexisting acoustic neuroma
      (AN) contributed to, and mutually modified, the course of sudden hearing loss. In
      the literature there are some reports pointing to a higher sensitivity to
      acoustic trauma in the case of patients with AN and, on the other hand,
      indicating noise as one of the causative factors in AN. Int J Occup Med Environ
      Health 2018;31(3):361-369.

PMID- 29184218
TI  - [Humor at Work Questionnaire - Polish adaptation of Humor Climate Questionnaire
      (HCQ)].
AB  - BACKGROUND: The aim of the paper is to present the Polish adaptation of the Humor
      Climate Questionnaire (HCQ), designed to measure humor as organizational climate
      feature. MATERIAL AND METHODS: The authors employed back-translation and
      independent judges method to choose the best version of the translated items. The
      psychometric properties of HCQ were estimated on the basis of 2 samples: the
      basic group of employees (N = 217) and the group of employees who had completed
      the survey twice (N = 55). RESULTS: The results of statistical analyses proved
      that HCQ is a reliable tool. Explorative Factor Analysis supported the 4-factor
      structure of the original method's theoretical model. The validity of the
      subscales is high, Cronbach's alpha varied from 0.8 to 0.9. The directions and
      values of intercorrelations between subscales were similar to those of the
      English version. The Humor Climate Questionnaire is a relatively time-stable tool
      (r = 0.44-0.74). CONCLUSIONS: Polish adaptation is reliable and applicable for
      cross-sectional studies. The obtained results are comparable to the
      characteristics of the original version. However, the results of factor analysis
      show that the data do not fully fit the theoretical model. Med Pr 2018;69(2):143
      152.

PMID- 29184219
TI  - Quality and biochemical changes of 'Hindi-Besennara' mangoes during shelf life as
      affected by chitosan, gallic acid and chitosan gallate.
AB  - Quality and biochemical changes of 'Hindi-Besennara' mangoes in response to
      chitosan, gallic acid (GA) and chitosan gallate (CG) postharvest dipping were
      studied during 2 weeks of storage at 20 +/- 2  degrees C and 60-70% RH. Both GA
      and CG lowered decay and weight loss during storage. Chitosan and GA at high
      level and CG at both level maintained higher membrane stability index of peel
      than control. Fruits treated only CG and GA at high level and chitosan at both
      levels retained higher acidity and vitamin C but lower pH and total soluble
      solids (TSS) than control. All treatments resulted with fruits with higher flesh
      firmness and lower TSS/acid ratio than untreated fruits. GA at both rates gave
      lower total phenols after 1 week of storage than control. Both levels of GA and
      low level of chitosan resulted with fruits with higher antioxidant capacity
      (lower IC50 values) after 1 week of storage than control. All treatments
      decreased alpha-amylase activity of fruit peel compared to control. CG and GA at
      high level and chitosan at low level increased peroxidase activity compared to
      control. It was concluded that CG and GA dipping delayed ripening and maintained
      quality of 'Hindi-Besennara' mangoes during 2 weeks of shelf life.

PMID- 29184220
TI  - Optimizing extraction conditions of crude fiber, phenolic compounds, flavonoids
      and antioxidant activity of date seed powder.
AB  - The objective of this study was to optimize the extraction conditions of crude
      fiber, phenolic compounds, flavonoids, and antioxidant activity from date seeds
      powder, using Response Surface Methodology. A central composite design with four
      independent variables; concentration of ethanol (X1 = 25, 50 and 75% v/v),
      solvent: sample ratio (X2 = 40:1, 50:1 and 60:1 v/w), temperature (X3 = 45, 55
      and 65  degrees C), and extraction time (X4 = 1, 2 and 3 h) and a three level
      face centered cube design were used. A total of twenty nine experimental runs
      with five replicates at the central point were used to study the response
      variables using two extraction cycles. Maximum phenolic compound content (71.6 mg
      GAE/100 g) was extracted using 50% ethanol solution with 40:1 solvent: sample
      ratio for 1 h at 55  degrees C. While the maximum antioxidant activity (55.02
      umol Fe(II)/g) was obtained using similar ethanol concentration and solvent:
      sample ratio except at lower temperature (45  degrees C) for 2 h. On other hand,
      the maximum flavonoids content (455.77 mg CEQ/100 g) was reached by using 50%
      concentration, 50:1 solvent: sample ratio at 65  degrees C for 3 h. In contrast,
      the content of fiber was not affected by the different extraction conditions.
      Results indicate that using combination of extracted conditions, have a great
      potential for extracting all depending compounds except crude fiber.

PMID- 29184221
TI  - Amino acid composition, antioxidant and functional properties of protein
      hydrolysates from Cucurbitaceae seeds.
AB  - In this study, the effect of enzymatic hydrolysis of globulin fraction of C.
      moschata (CMH), C. lanatus (CLH) and L. siceraria (LSH) on antioxidant capacity,
      functional properties, structural and micro-structural properties, as well as
      amino acid compositions were evaluated. All the hydrolysates exhibited
      significant antioxidant properties. The essential amino acids content in LSH
      (92.7 mg/g) was higher than CMH (79.9 mg/g) and CLH (70.5 mg/g). Water absorption
      capacity (5 g/g), heat stability (89%), emulsifying activity index (98.3 m2/g)
      and emulsifying stability index (45.1 min) were statistically more significant
      for LSH as compared to CMH and CLH. In addition, LSH had significantly higher FS
      and FC at pH 3-9. Among all hydrolysates, LSH showed highest solubility (87.3%)
      as compared to other hydrolysates. The results suggested that enzymatic
      hydrolysis improve the antioxidant and functional properties. Thus, the globulin
      hydrolysates might be served as an innovative source with promising nutritive
      values, good antioxidant and functional properties. Moreover, these could be used
      in food and pharmaceutical industries for the development of novel functional
      foods.

PMID- 29184222
TI  - Naturally occurring folates in selected traditionally prepared foods in Southern
      India.
AB  - A wide range of Indian foods (cereals, pulses, vegetables and milk based
      preparations) were analysed for five folate vitamers naturally present in the
      foods (n = 44). A liquid chromatography-mass spectrometry (LC-MS/MS) method using
      reversed phase chromatography and tandem mass spectrometry, coupled via positive
      mode electrospray ionization was used for the detection and quantification of the
      vitamers. The optimized LC-MS/MS method was capable of analysing the five most
      commonly-occurring folates (folic acid, 5-methyl tetrahydrofolic acid,
      tetrahydrofolic acid, 10-formyl folic acid and 5-formyl tetrahydrofolic acid) in
      20 min. Quantification of folates was performed using 13C labelled internal
      standards. 5-methyl tetrahydrofolate was predominant in cereals, pulses and
      vegetable preparations. Fermented cereal preparations, beverages (coffee and tea)
      and green leafy vegetables were the main sources contributing to 5-formyl THF.
      Folic acid was identified in home-made yoghurt. All the values obtained in the
      present study using LC-MS/MS were compared to the total folate analysed using the
      microbiological assay in 2010 to generate data on the same foods. Findings
      suggest that the data obtained using both techniques showed agreement in the
      values (total folate calculated by adding the individual vitamers in the case of
      the LC-MS/MS values) particularly when foods were predominant in 5 methyl
      tetrahydrofolate.

PMID- 29184223
TI  - Properties of spray-dried fish oil with different carbohydrates as carriers.
AB  - This study evaluated the application of cashew gum, Arabic gum and starch on
      physical and thermal properties, and fatty acid profiles of spray-dried fish oil.
      A completely randomized design was used to evaluate the influence of the type of
      material on the properties of the microparticles. Hygroscopicity and solubility
      was higher for particles produced using cashew gum and reached 15 g/100 g and 85
      g/100 g, respectively. Analyzing the thermogravimetric curves, it was found that
      cashew gum bulk showed two steps of degradation. For the microcapsules containing
      encapsulated fish oil in cashew gum, an extra degradation step at 471  degrees C
      was found. It was possible to verify the occurrence of diffused and wide peaks in
      the X-ray diffractograms for all three carbohydrate polymers. The particles
      produced presented spherical shape with cavities. The fatty acid profile for the
      fish oil changed only when using modified starch as wall material, where a
      significant loss of omega-3 fatty acids was observed. The particles produced with
      cashew gum had physical properties similar to those when applying materials
      commonly used and this biopolymer has the potential for application as a carrier
      in spray drying processes .

PMID- 29184224
TI  - Performance, carcass traits, meat quality and amino acid profile of different
      Japanese quails strains.
AB  - Poultry production is considered one of the prospective opportunities to
      accomplish sustainable and quick production of superior protein to challenge the
      growing mandate for animal protein. Therefore, this study was aimed to explore
      the difference on growth performance, carcass traits, meat quality and amino acid
      profile of different Japanese quails strains. A total of 480 quail chicks of four
      different plumage colors (120 of each white, golden, gray and brown) were
      collected after hatching. At 6 week of age, birds were stunned and decapitated to
      determine the physical meat quality, thiobarbituric acid reactive substances and
      amino acid profile. White quails had the highest weight of slaughter, carcass,
      dressing, carcass yield, liver, gizzard, heart and spleen (197.27 g, 169.27 g,
      91%, 82%, 6.63 g, 6.53 g, 2.27 g and 0.40 g, respectively). Also, they had the
      highest PhU, lightness, yellowness and water holding capacity with the lowest
      level of redness, cooking losses and thiobarbituric acid in pectoral (6.28,
      46.40, 12,46, 22.17, 9.20, 19.21 and 0.44, respectively) and thigh muscles (6.37,
      42.30, 11.51, 26.01, 10.12 and 0.93, respectively). Moreover, they possessed the
      highest level of all essential (11.68 and 10.16 g/100 g protein in pectoral and
      thigh muscles, respectively) and non essential amino acids (13.27 and 12.54 g/100
      g protein in pectoral and thigh muscles, respectively). Therefore, the current
      study revealed that white quails had the heaviest body weight with the best
      carcass traits and meat quality.

PMID- 29184225
TI  - Thermodynamic and kinetics study of phenolics degradation and color of yacon
      (Smallanthus sonchifolius) microparticles under accelerated storage conditions.
AB  - This study aimed to investigate the kinetics and thermodynamic of the phenolics
      degradation and the kinetics of degradation of the total color difference of
      yacon juice microcapsules produced by spray drying using Gum Arabic and
      polydextrose as wall materials. The degradation of the microcapsule was evaluated
      by accelerated tests under controlled conditions at 35 and 45  degrees C, and
      relative humidity of 75 and 90%, for 35 days. Degradation of phenolics followed
      the first order model and the degradation constant was in the range of 0.0124
      0.0209 days-1. The microparticles with gum Arabic were more stable than those
      with polydextrose for all conditions studied, with longer half-lives. Both wall
      materials showed similar thermodynamic characteristics, indicating similar
      mechanism of degradation of phenolics. With respect to the color parameters, the
      first order model adjusted to data of the total color difference, and no
      significant differences were observed for the conditions studied.

PMID- 29184226
TI  - Antioxidant activity and protective effect of bee bread (honey and pollen) in
      aluminum-induced anemia, elevation of inflammatory makers and hepato-renal
      toxicity.
AB  - Aluminum toxicity might be related to oxidative stress, and the antioxidant
      activity and protective effect of bee bread, which contains pollen, honey and
      bees' enzymes, on aluminum induced blood and hepato-renal toxicity was
      investigated in rats. Chemical analysis and antioxidant capacity of bee bread
      were conducted. The animal experiment in rats included; group 1: received
      distilled water (10 ml/kg b.wt), group 2: received aluminum chloride (662.2 mg/kg
      b.wt), group 3: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic
      extract of the bee bread (500 mg/kg b.wt), and group 4: received aluminum
      chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (750 mg/kg
      b.wt). Doses were given once daily via a gavage. C-reactive protein,
      transaminases, urea, creatinine, creatinine clearance, sodium and potassium and
      urine sodium and potassium were determined on day 28 of the experiment. Bee bread
      contained protein, fat, fiber, ash, carbohydrate, phenol and flavonoids and it
      exhibited antioxidant activity. Aluminum caused a significant elevation of blood
      urea, transaminase, C-reactive protein and monocyte count and significantly
      decreased hemoglobin. These changes were significantly ameliorated by the use of
      bee bread. Bee bread has an antioxidant property, and exhibited a protective
      effect on aluminum induced blood and hepato-renal toxicity and elevation of
      inflammatory markers C-reactive protein, leukocyte and monocyte counts.

PMID- 29184227
TI  - Construction of a lateral flow strip for detection of soymilk in milk.
AB  - A lateral flow based detection method for ascertaining the presence of soymilk in
      whole bovine milk has been described. The method uses commercially available
      rabbit anti-soy protein antibodies conjugated to gold nanoparticles (AuNPs)
      wherein soymilk protein in adulterated milk and soymilk protein at test line
      competes for limited antibodies. At control line, anti-rabbit immunoglobulin was
      immobilized for ensuring flow properties of antibody-conjugated AuNPs. Absence or
      diminished intensity of band at test line indicates presence of soymilk in milk.
      The soymilk detection limit was 1.75% (v/v) in whole bovine milk and results are
      available in 5 min. Constructed lateral flow device can be used for on-spot
      examination of soymilk in milk.

PMID- 29184228
TI  - Development of sweet and sour chicken meat spread based on sensory attributes:
      process optimization using response surface methodology.
AB  - Now a day's meat and meat products are not only generating convenience trends;
      they have been recognized as core of meat industry. Meat spread is a convenience
      cooked spreadable product prepared with meat and non-meat additives. Response
      surface methodology was used to investigate the effects of three different levels
      of honey (10, 15, 20 g), vinegar (2.0, 6.0, 10.0 ml) and tomato powder (0.5, 1.0,
      1.5 g) on response variables viz. color/appearance, flavor, spreadability,
      texture, after taste, adhesiveability, overall acceptability, while standardizing
      the process of development of sweet and sour chicken meat spread box-behnken
      experimental design was used in which 17 different runs with 5 trials of three
      similar centre point. A second order polynomial was fitted to all the response
      variables and surface plots as well as equations were conducted. All the
      processing variables significantly affected the response variables either
      linearly or quadratically whereas the "Lack of Fit" was non-significant relative
      to the pure error. For optimization, target values were set in the form of ranges
      of all the processing and response variables. While applying multiple regression
      analysis, a total of 43 workable solutions was found, out of which the product
      with 14.28% honey, 5.38% vinegar and 1.39% tomato powder was selected. The
      responses for color/appearance, flavor, spreadability, texture, after taste,
      adhesiveability, overall acceptability, were predicted at 7.11, 6.72, 7.00, 6.99,
      6.61, 6.94 and 6.79 respectively, with a desirability value of 1.

PMID- 29184229
TI  - Effect of soaking and germination on physicochemical and functional attributes of
      horsegram flour.
AB  - Horsegram is an underutilized pulse, traditionally used for treating various
      disorders like kidney stones, diabetes and joint pain. The present study was
      undertaken to optimize the soaking and germination conditions, to decrease the
      anti-nutritional factors and at the same time maintaining the nutritional
      properties of horsegram. Horsegram seeds were soaked for 6, 12 and 18 h followed
      by germination for 0, 24 and 48 h under different illumination conditions i.e.,
      light and dark respectively. The soaked and germinated samples were dried in
      laboratory drier at 55  degrees C until constant moisture was achieved and was
      further analyzed for various quality attributes. Almost all the physicochemical
      and functional characteristics were significantly affected by both soaking and
      germination, whereas, germination done in light and dark conditions, exerted
      significant effect on the ascorbic acid content, total protein, total phenols,
      antioxidant activity and tannin content only. Based on the quality attributes, it
      was found that treatment having 18 h soaking and 48 h germination in the presence
      of light was the best where maximum decrease in the anti-nutritional factors was
      observed. Moreover, there was an increase in ascorbic acid, total protein content
      and a decrease in the anti-nutritional factors such as oxalate and tannin
      content. Thus, it is concluded that 18 h soaking and 48 h germination in the
      presence of light can be considered as the optimum conditions to increase the
      nutritional content of horsegram flour, which can further be utilized for the
      preparation of different value-added food products.

PMID- 29184230
TI  - Authentication of Romanian honeys based on physicochemical properties, texture
      and chemometric.
AB  - The purpose of this study was to investigate the physico-chemical properties
      (free acidity, pH, aw, ash content, moisture content, color (L*, a*, b*, hue
      angle, chroma and yellow index), fructose, glucose and sucrose content) and
      textural parameters (viscosity, hardness, adhesion, springiness, cohesiveness,
      chewiness and gumminess) of 50 samples of honey of different botanical origin
      (acacia, polyfloral, honeydew, sunflower and tilia). In order to achieve the
      authentication of the honey samples analyzed, their data have been subjected to
      linear discriminant analysis (LDA) and principal component analysis (PCA).The PCA
      and LDA have proved the possibility of honey authentication using the physico
      chemical and textural properties. LDA classified correctly 92.0% of the honeys
      based on their botanical origin, using the cross validation. In the LDA
      projection, the textural parameters (chewiness, hardness, cohesiveness,
      springiness) dominated the two functions.

PMID- 29184231
TI  - Transitions in mesocarp colour of mango fruits kept under variable temperatures.
AB  - The impact of variable temperatures on mesocarp colour development and physico
      chemical changes of mango fruits cv. Langra during ripening has been
      investigated. Physiological mature mango fruits were kept in temperature
      regulated chambers (20 and 25  degrees C) and at room temperature (29.8-33.6 
      degrees C). Progress in development of mesocarp colour, beta-carotene, sensory
      quality (SQ) and total soluble solids (TSS) content of fruits were analysed
      periodically from 48 to 168 h of ripening period. The progress of ripening period
      was accompanied by an overall increase in colorimetric value redness (a*),
      yellowness (b*), chroma or saturation (C*), a reduction in lightness (L*) and hue
      angle (h0) values. Colour development was found to be more in fruits ripened at
      higher temperatures than the fruits at lower temperature. beta-carotene content
      of pulp improved with ripening of fruits up to 120 h of ripening period. Fruits
      ripened at 25  degrees C recorded maximum sensory quality score. Pearson's
      correlation matrix studies revealed that fruit mesocarp colour a*, b*, C* values
      were directly correlated with beta-carotene, SQ and TSS with progress of ripening
      period.

PMID- 29184232
TI  - Antioxidant, functional properties and amino acid composition of pepsin-derived
      protein hydrolysates from whole tilapia waste as influenced by pre-processing ice
      storage.
AB  - In recent years, hygienic handling of fishery waste is demanded owing to the fact
      that the fishery waste is an ideal raw material for the preparation of bioactive
      compounds. In the present study, the effect of pre-processing storage (at 4 +/- 2
      degrees C) of whole tilapia waste (WTW) on the properties of its protein
      hydrolysate derived using pepsin was evaluated. Fish protein hydrolysates (FPH)
      were prepared from 0, 24 and 48 h old ice stored WTW and designated as FPH-0, FPH
      1, and FPH-2, respectively. Total amino acids, total essential amino acids and
      total hydrophobic amino acids of FPH samples increased with the storage period of
      raw material (WTW). Antioxidant activities such as DPPH (2, 2 diphynyl-1
      picrylhydrazyl) free radical scavenging activity and ferric reducing power of FPH
      samples were dose dependent. FPH-0 had better antioxidant properties including
      linoleic acid peroxidation inhibition activity than FPH-1 and FPH-2. The DNA
      nicking assay revealed the protective effect of FPH preparations against Fenton's
      reaction mediated oxidative damage. FPH-2 had better emulsifying properties and
      foaming stability whereas the FPH-0 had relatively good foaming capacity. SDS
      PAGE indicated the presence of peptides ranging from 116 to < 14.4 kDa in FPH-0
      and less than 18 kDa in FPH-1 and FPH-2. The present study, clearly demonstrated
      that whole tilapia waste can effectively be converted to FPH and could be a
      potential ingredient in functional food and as a rich source of high-quality
      protein in animal feed formulations.

PMID- 29184234
TI  - The effect of gamma irradiation on the properties of cucumber.
AB  - In this study, the effect of gamma irradiation on the shelf life and properties
      of cucumber was investigated. These properties include weight reduction, fruit
      density, juice, tissue firmness, total soluble solids (TSS), total titratable
      acidity, chlorophyll and vitamin C, pH, marketability, flavor, frostbite and
      fungal effects. For this purpose, cucumbers were irradiated with dose of 2, 2.5
      and 3 kGy. The exposure time was calculated by MCNP4C; the Monte Carlo particle
      transport code. Three types of fungi (white-Sclerotinia sclerotiorum, gray
      Botrytis cinerea and olive-Cladosporium cucumerinum), were used to infect some
      samples. The chlorophyll and vitamin C preservation abilities were increased to
      about 3 and 1.4 times, respectively with irradiation treatment. Also, the shelf
      life was increased about 1 week, while chilling injuries is decreased. Samples'
      resistance to the fungal growth was evident and the process of fungal growth on
      the irradiated samples was delayed up to 1 week. The best properties were
      obtained at the irradiation dose of 2 kGy since it had less effect on flavor, TSS
      and tissue firmness.

PMID- 29184233
TI  - Biofunctional properties of bioactive peptide fractions from protein isolates of
      moringa seed (Moringa oleifera).
AB  - Moringa oleifera (Moringaceae) is a specie of significant importance because of
      its multiple nutraceutical properties, that has led to increase in its
      consumption. The seeds contain a high percentage of protein (37.48%). However,
      little is known about the bioactive properties of these proteins and peptides,
      especially those generated by enzymatic hydrolysis. The objective of this study
      was to evaluate the biofunctional properties of total hydrolysates (TH) and
      peptide fractions from protein isolates of moringa seeds. Isoelectric protein
      isolates were prepared and TH were obtained by digestion with trypsin,
      chymotrypsin and pepsin-trypsin for 2.5 and 5 h. TH were fractioned by
      ultrafiltration (UF) with a 10 kDa membrane to generate the peptide fractions. In
      all treatments, the antioxidant capacity was significantly higher in peptide
      fractions > 10 kDa with 5 h of hydrolysis. The results showed that the fraction >
      10 kDa of pepsin-trypsin digested for 5 h presented a better Angiotensin
      Converting Enzyme inhibition (ACE-I) activity with an IC50 of 0.224 MUg/MUl.
      Also, antidiabetic activity was enhanced in pepsin-trypsin treatment with 5 h of
      hydrolysis showing an IC50 of 0.123 MUg/MUl. Finally, this study showed that
      hydrolysates of moringa seed proteins had excellent in vitro nutraceutical
      potential.

PMID- 29184235
TI  - Volatile fingerprinting of the plum brandies produced from different fruit
      varieties.
AB  - Nowadays, fingerprinting of food became one of the most perspective analytical
      tools to resolve a problem of food quality and authentication, especially in
      difficult cases like differentiation of fruit varieties. In this work, plum
      brandies distillated by the same technology from 25 plum cultivars were
      distinguished by comprehensive two-dimensional gas chromatographic analysis and
      sensory evaluation. The number of identified compounds in studied samples varied
      between 91 and 195 depending on the plum variety. Enriched volatile organic
      compounds (VOC) profile was identified for the samples received from "Chrudimer",
      "Cacak Fruitful" and "Hanita" plum varieties, whereas in the case of "Gabrovska",
      "Presenta", Elena" and "President" plum varieties, the VOC profile was
      significantly reduced. From qualitative point of view, the particular plum
      brandies showed differences in the presence of unsaturated fusel alcohols (e.g. 3
      methyl-3-buten-1-ol, trans-3-hexenol), unsaturated aldehydes (2-butenal, 2
      nonenal), monoterpene derivatives (e.g. linalool acetate, geraniol acetate) and
      lactones, which were mainly detected at the trace level.

PMID- 29184236
TI  - Optimization of extraction process of inulin from Indian millets (jowar, bajra
      and ragi)-characterization and cost analysis.
AB  - Prebiotic biomolecule, namely, inulin was extracted from Indian millets, namely,
      jowar (Sorghum vulgare), bajra (Pennisetum glaucum) and ragi (Eleusine coracana).
      Through qualitative assessment using Fourier Transform Infrared spectroscopy, the
      presence of functional groups of inulin in the above mentioned Indian millets
      were verified. The values of degree of polymerization of inulin derived from
      jowar, bajra and ragi were determined to be 27, 39 and 23 respectively. A
      comparative analysis of growth of Lactobacillus casei was carried out in presence
      of both lactose and inulin extracted from three millets and the commercial one.
      It was observed that the bajra inulin and lactose combination exhibited the best
      bacterial growth. The prebiotic effectiveness of different varieties of inulin
      was calculated to be in the following order: bajra > jowar > ragi > commercial
      inulin. Therefore the results on bajra inulin were highlighted in this article.
      Inulin yield from bajra was optimized as a function of temperature, HCl
      concentration and heating period. The maximum inulin yield (0.4727 g/g bajra) was
      obtained at temperature 70  degrees C, HCl concentration of 0.8 M and heating
      period of 60 min. The prebiotic activity score of bajra inulin (= 3.2) was
      measured to be much higher than commercial inulin (= 1.0). Growth dynamics of
      Lactobacillus casei on lactose, bajra inulin and mixture of lactose and bajra
      inulin were found to be of Monod type, Haldane type and Multi-substrate-summative
      type respectively. The techno-economic analysis based on the production cost of
      inulin from raw bajra seeds suggested that it was much cheaper than commercial
      inulin.

PMID- 29184237
TI  - Identification of bioactives from Astragalus chinensis L.f. and their
      antioxidant, anti-inflammatory and anti-proliferative effects.
AB  - This work was designed to obtain the valuable compounds with antioxidant, anti
      proliferative and anti-inflammatory activities from Astragalus chinensis. Ethyl
      acetate fraction obtained from A. chinensis L.f. had significant antioxidant,
      anti-proliferative and anti-inflammatory activities. Subsequently, five single
      compounds were separated and purified, which were identified as formononetin (1),
      rhamnocitrin (2), calycosin (3), beta-daucosterol (4), rhamnocitrin-3-O-beta-d
      glucoside (5). The results displayed that formononetin and rhamnocitrin exhibited
      significant cytotoxicity actions against tumor cell lines. Calycosin exerted the
      strongest anti-inflammatory effect of inhibition effects on NO production in
      macrophages.

PMID- 29184238
TI  - Effect of natural antioxidants on physicochemical properties and lipid stability
      of pork liver pate manufactured with healthy oils during refrigerated storage.
AB  - This study aimed to evaluate the effect of natural antioxidants in pork liver
      pate manufactured with the combination of pork backfat, fish oil and olive oil.
      Phenolic composition of beer residue extract (BRE), chestnut leaves extract (CLE)
      and peanut skin extract (PSE) were identified and quantified. Four batches of
      pork liver pate were produced: control, BRE, CLE and PSE. Pork liver pate was
      evaluated for proximate composition, pH, instrumental colour, free fatty acid
      content, lipid-derived volatile compounds and lipid oxidation. The major
      compounds of BRE were benzoic acid and catechin (1.79 and 1.51 mg/L,
      respectively), in CLE were ellagic and gallic acid (10.26 and 2.70 mg/100 g fresh
      weight) and in PSE was catechin (20.66 mg/100 g dry weight). Proximate
      composition was similar for all batches. The pH values were not influenced by any
      natural antioxidant. Colour parameters were affected by storage time but slight
      differences were observed among batches. Lipid stability (TBARS and lipid-derived
      volatile compounds) was not remarkably affected by addition of natural extracts.

PMID- 29184239
TI  - Effect of heating on oxidation stability and fatty acid composition of microwave
      roasted groundnut seed oil.
AB  - The oxidative stability and fatty acid composition of groundnut seed oil (GSO)
      exposed to microwaves were evaluated during heating at 170  degrees C. During
      heating, the oxidative indices such as free fatty acid, peroxide value, p
      anisidine value, TOTOX, thiobarbituric acid value, specific extinctions, and
      color value were increased. The increments were found to be higher in unroasted
      seed oils compared to roasted ones indicating lower release of lipid oxidation
      products in roasted GSO. After 9 h heating, the relative content of
      polyunsaturated fatty acid (PUFA) decreased to 89.53% and that of saturated fatty
      acid (SFA) increased to 117.46% in unroasted sample. The relative content of PUFA
      decreased to 92.05% and that of SFA increased to 105.76% in 7.5 min roasted
      sample after 9 h of heating. However, the roasting process slowed down the
      oxidative deterioration of PUFA. With increased heating times, an appreciable
      loss was more apparent in the triacylglycerol species OLL and OOL in unroasted
      samples compared to roasted ones. In FTIR, the peak intensities in unroasted
      samples were markedly changed in comparison with roasted samples during heating.
      The roasting of groundnut seed prior to the oil extraction reduced the oxidative
      degradation of oil samples; thereby increasing heat stability.

PMID- 29184240
TI  - Essential oils as antibacterial agents against food-borne pathogens: Are they
      really as useful as they are claimed to be?
AB  - Most studies evaluating the use of essential oils (EO) as antibacterial agents
      focus mainly on minimal inhibitory concentrations (MIC) rather than minimal
      bactericidal concentrations (MBC). In this work, we compared MICs and MBCs of EO
      from condiment plants commonly used in Mediterranean Europe, namely Origanum
      vulgare, Salvia lavandulaefolia, Salvia officinalis, Salvia sclarea and
      Rosmarinus officinalis, aiming to evaluate their application as disinfecting
      agents in minimally processed produce. Outbreaks-related pathogens such as
      Listeria monocytogenes, Pseudomonas aeruginosa and Yarrowia lipolytica were used.
      Results showed that all EO were able to reduce bacterial growth in all bacterial
      strains tested, particularly O. vulgare. However, fewer EO exhibited bactericidal
      activities, and were only effective against one or two bacterial strains, hence
      eliminating the possibility to use them as broad range disinfectants.
      Furthermore, the necessary concentrations were too high for food application.
      Hence, our work suggests the need to evaluate MBC rather than MIC and questions
      EO usefulness in controlling undesired microorganisms. Overall, and despite the
      large volume of data published on EO, results obtained were not very encouraging
      for a realistic application on produce and question the viability of EOs as
      disinfecting agents in food.

PMID- 29184241
TI  - Effect of different operating conditions in cloud point assisted extraction of
      thymol from Ajwain (Trachyspermum Ammi L.) seeds and recovery using solvent.
AB  - Cloud point assisted extraction of thymol from water extract of Ajwain
      (Trachyspermum Ammi L.) seeds has been reported. Effects of different operating
      conditions, i.e., concentration of surfactant, heating time and temperature in
      extraction efficiency were investigated. It was observed that maximum extraction
      efficiency of thymol was achieved with 30% (v/v) of SPAN 80 surfactant, 45 min of
      heating at 65  degrees C. Recovery of thymol from the surfactant complex was
      optimal at 1:3 coacervate phase to solvent (acetone) volume ratio. A semi
      empirical correlation was proposed at the optimum time to predict the
      concentration of surfactant and temperature required for a desired yield.

PMID- 29184242
TI  - Antioxidant capacity and identification of bioactive compounds of Myrtus communis
      L. extract obtained by ultrasound-assisted extraction.
AB  - Ultrasound-assisted extraction was used to investigate the polyphenolic
      compounds, particularly anthocyanins, present in myrtle alcoholic extracts. This
      type of extract is typical in the making of liqueurs obtained from herbs or
      plants, especially medicinal plants. The leaf extracts were found to contain
      flavonoids from the quercetin and myricetin families. Besides these, the berry
      extracts also showed the presence of anthocyanins, hydrolysable tannins and
      quinic acid. The antioxidant capacity was studied using the ORAC and TEAC methods
      and the polyphenol content was measured using the Folin-Ciocalteu method. The
      results showed that the values produced by the ORAC and TEAC methods were in
      agreement and that the antioxidant capacity correlated with the polyphenol
      content. The results showed that the leaf extracts exhibited higher antioxidant
      capacity than the berry extracts. The extraction method was easily implementable,
      and proved to be a swift method for obtaining bioactive compounds from vegetable
      matrices.

PMID- 29184243
TI  - Starch digestibility and glycemic index of Paranthas supplemented with Citrus
      maxima (Burm.) Merr. fruit segments.
AB  - The present investigation was undertaken to develop paranthas suiting diabetic
      population with added health benefits. Paranthas were prepared using fresh and
      dry segments of pomelo. The increase in the concentration of segments decreased
      the texture value from 1080 to 1022 g force (fresh segments) and 1005 to 870 g
      force (dry segments). Naringin along with other bioactive compounds were retained
      to a greater extent in Paranthas containing dry pomelo fruit segments. Paranthas
      prepared using 20% (fresh) and 5% (dry) were sensorily acceptable. The pomelo
      incorporated paranthas had higher levels of resistance starch fractions (12.94%)
      with low predicted glycemic index (49.89%) compared to control Paranthas at 5.54
      and 58.64% respectively. The fortified paranthas with an considerable content of
      bioactive compounds and low glycemic index indicate the possibility of using it
      as a dietary supplement. Thus utilization of pomelo fortification helps in
      improving the nutritional and functional property of paranthas suiting diabetes
      as well as general population.

PMID- 29184244
TI  - Assessment of inhibitory factors on bioaccessibility of iron and zinc in pearl
      millet (Pennisetum glaucum (L.) R. Br.) cultivars.
AB  - The variations in iron and zinc bioaccessibility as influenced by inhibitory
      factors in 13 pearl millet cultivars were evaluated. The results indicated that
      iron and zinc contents ranged between 5.59-13.41 and 2.11-5.19 mg/100 g.
      Polyphenols, flavonoids and phytic acid were highest in GHB744 (781 mg/100 g),
      HHB223 (116 mg/100 g) and HHB226 (1.080 g/100 g) respectively. Insoluble fiber
      content range from 9.36 to 12.89 g/100 g. Iron and zinc bioaccessibility was the
      highest in local Anantapur (17.95%) and GHB744 (15.19%) cultivar with low phytic
      acid. HHB226 exhibited high beta-carotene and phytase activity. In this study,
      the cultivars with high iron and zinc content also possessed high inhibitory
      factors which affected bioaccessibility. However, the bioaccessibility of iron
      did not seem to depend on the phytic acid: iron ratio alone. Further, a trend was
      observed in cultivars with low iron: zinc ratio had increased iron
      bioaccessibility. On the contrary, phytic acid: zinc ratio appears to play a
      significant role in zinc bioaccessibility. Certain cultivars with high iron
      content also had high phytase activity and beta-carotene content which could be
      exploited for further technological treatments to enhance the bioaccessibility of
      iron and zinc.

PMID- 29184245
TI  - beta-Lactoglobulin microparticles obtained by high intensity ultrasound as a
      potential delivery system for bioactive peptide concentrate.
AB  - This work attempted to assess the effect of high intensity ultrasound (HIUS) upon
      development of bio-based delivery systems, from beta-lactoglobulin (beta-Lg)
      gelled microparticles, for encapsulation of a bioactive peptide concentrate
      (PepC). Solutions of 150 g L-1 of commercial beta-Lg and 30 g L-1 PepC, at
      various pH values (3.0, 4.0 and 5.5), were accordingly subjected to gelation for
      30 min using a dry bath kept at 80  degrees C. The gelled systems were then
      exposed to HIUS at 0-4  degrees C, and the effect of processing time (2.5-20.0
      min) was ascertained. Laser light scattering and confocal microscopy were used to
      characterize the particle size distribution, prior to and immediately after HIUS
      treatment. Gels obtained at pH 5.5 and 4.0 were harder than those obtained at pH
      3.0. Ultrasound treatment of gels produced an important reduction in particle
      mean diameter as sonication time elapsed. Confocal microscopy indicated that
      application of HIUS led to almost round and monodispersed particles, at both pH
      5.5 and 4.0. The peptide encapsulation efficiency was assessed by chromatography
      and accompanied by assay for bioactivity, after precipitation of the encapsulated
      material and analysis of the soluble peptides therein.

PMID- 29184246
TI  - Effect of desiccant system on thin layer drying kinetics of corn.
AB  - Drying is one of the most important post-harvest processes for reducing the
      moisture content of agricultural products and improving their performance has
      obvious benefits. Most dryers are convective type in which hot air is used for
      reduction of product moisture content. Effect of adding a desiccant unit to a re
      circulating convective dryer on thin layer drying kinetics of corn kernels is
      reported here. The influence of the desiccant unit, drying temperature and flow
      rate on drying time, moisture diffusivity coefficient and reactivation energy
      were investigated. The experiments were conducted at air temperatures of 50, 60
      and 70  degrees C and flow rates of 1, 1.4 and 1.8 kg/min with and without the
      desiccant unit. Results showed that the use of the desiccant wheel decreased
      drying time by 9.75% and increased drying rate by 7.85%. Application of a
      Logarithmic model for fitting the data, while being simple, resulted in good
      statistical indexes (R2 and RMSE). Moisture diffusivity coefficient was obtained
      to be in the 3.47258 * 10-11 to 8.18826 * 10-11 m2/s range, while activation
      energy varied between 14.2931 and 17.6770 kJ/mol on the average. Therefore,
      utilization of the desiccant unit accelerates moisture extraction from corn
      samples.

PMID- 29184247
TI  - Effect of packaging types and storage conditions on quality aspects of dried
      Thunbergia laurifolia leaves and degradation kinetics of bioactive compounds.
AB  - Thunbergia laurifolia leaves were dried by freeze drying (FD) and microwave heat
      pump dehumidified air drying (MHPD). The dried leaves were stored in
      polypropylene (PP) or aluminum laminated pouches (ALP) at 15, 25 or 35  degrees C
      and 60% RH. The samples were held for 180 days to observe changes in moisture
      content, color, total phenolics, antioxidant activity, catechin and caffeic acid.
      In general, samples in PP had a greater increase in moisture. Total phenolics
      content and ferric-reducing antioxidant power values increased for 120 days, then
      decreased thereafter. After 180 days, both FD and MHPD samples packaged in ALP
      and stored at 15  degrees C had the greatest total phenolics, antioxidant
      activity and bioactive compounds amongst the storage conditions. The first-order
      equation best described degradation behavior of catechin and caffeic acid for
      both drying technologies investigated.

PMID- 29184248
TI  - Differential accumulation of beta-carotene and tissue specific expression of
      phytoene synthase (MaPsy) gene in banana (Musa sp) cultivars.
AB  - An experiment was conducted with twelve major Indian banana cultivars to
      investigate the molecular relationship between the differential accumulation of
      beta-carotene in peel and pulp of the banana fruit and carotenoid biosynthetic
      pathway genes. The high performance liquid chromatography showed that all banana
      cultivars accumulated two-three fold more beta-carotene in non-edible portion of
      the banana fruit. However, Nendran, a famous orange fleshed cultivar of South
      India, had high beta-carotene content (1362 ug/100 g) in edible pulp. The gene
      encoding Musa accuminata phytoene synthase (MaPsy) was successfully amplified
      using a pair of degenerate primers designed from Oncidium orchid. The deduced
      amino acid sequences shared a high level of identity to phytoene synthase gene
      from other plants. Gene expression analysis confirmed the presence of two
      isoforms (MaPsy1 and MaPsy2) of MaPsy gene in banana fruits. Presence of two
      isoforms of MaPsy gene in peel and one in pulp confirmed the differential
      accumulation of beta-carotene in banana fruits. However, Nendran accumulated more
      beta-carotene in edible pulp due to presence of both the isoforms of MaPsy gene.
      Thus, carotenoid accumulation is a tissue specific process strongly dependent on
      differential expression pattern of two isoforms of MaPsy gene in banana.

PMID- 29184249
TI  - Spray drying egg using either maltodextrin or nopal mucilage as stabilizer
      agents.
AB  - In this work, a comparative study between spray drying (SD) of fresh egg by
      either maltodextrin (MD) or nopal-mucilage (MN) as stabilizing vectors was made.
      The powders obtained were characterized for drying performance, moisture content,
      chemical proximate analysis, thermal analysis (TGA), chemical composition (FTIR),
      microscopy (SEM) and rheology (viscoelasticity and steady state simple shear
      viscosity). Infrared analysis showed that MN has the effect of a thickening agent
      rather than an encapsulating one. Results indicated that SD egg with MN produced
      a high thermal and mechanical stable product and rendered the highest drying
      performance, producing a more uniform and defined sphere-shaped morphology in
      comparison to egg SD either alone and with MD.

PMID- 29184250
TI  - Pecan walnut (Carya illinoinensis (Wangenh.) K. Koch) oil quality and phenolic
      compounds as affected by microwave and conventional roasting.
AB  - In this study, the effects of conventional and microwave roasting on phenolic
      compounds, free acidity, peroxide value, fatty acid composition and tocopherol
      content of pecan walnut kernel and oil was investigated. The oil content of pecan
      kernels was 73.78% for microwave oven roasted at 720 W and 73.56% for
      conventional oven roasted at 110  degrees C. The highest free fatty acid content
      (0.50%) and the lowest peroxide value (2.48 meq O2/kg) were observed during
      microwave roasting at 720 W. The fatty acid profiles and tocopherol contents of
      pecan kernel oils did not show significant differences compared to raw samples.
      Roasting process in microwave oven at 720 W caused the reduction of some phenolic
      compounds, while the content of gallic acid exhibited a significant increase.

PMID- 29184251
TI  - Changes in nutritional and physico-chemical properties of pearl millet
      (Pennisetum glaucum) Ex-Borno variety flour as a result of malting.
AB  - The effect of malting periods on the nutritional composition and physico-chemical
      properties of flour from pearl millet (Ex-Borno) variety was evaluated. Grains
      were steeped at 25  degrees C for 24 h and germinated for different durations
      (12, 24, 36, 48, 60, 72, 84 and 96 h) before kilning at 55  degrees C for 18 h.
      The kilned seeds were devegetated, milled, sieved and analysed for their
      proximate composition, amino acid composition, total phenolic content, functional
      and pasting properties. The carbohydrate, fat and total phenolic contents of the
      pearl millet flour samples decreased while protein content increased with
      increased malting periods. Leucine was the dominant amino acid in the flour and
      48 h-malted flour had the highest total amino acid (6.72). Peak viscosity
      significantly decreased as the malting period increased. Solubility index,
      pasting temperature and phenolic content of the flours ranged from 5.13 to
      17.24%, 69.05 to 89.5  degrees C and 130.20 to 169.90 mg/100 g, respectively.
      Malting offers a means of improving the nutritional profile of Ex-Borno pearl
      millet flour with an increased protein and fibre and reduced fat content. Malting
      also enhanced the functional and pasting properties of the flour.

PMID- 29184252
TI  - Development and characterization of couscous-like product using bulgur flour as
      by-product.
AB  - Couscous is produced traditionally by agglomeration of Triticum durum semolina
      with water. The aims of this study were: to produce couscous-like product by
      substitution of semolina with bulgur by-product (undersize bulgur); to find
      optimum quantity of bulgur flour and processing conditions. In order to determine
      the optimum processing parameters and recipes; 0, 25 and 50% of bulgur containing
      couscous-like samples were prepared. The color, yield, sensory properties, total
      phenol and flavonoid contents, bulk density, protein and ash content, texture
      properties were determined. Two different types of dryer e.g. packed bed and
      microwave were used. Optimum parameters were predicted as 50% of bulgur flour for
      packed bed (60  degrees C) and microwave (180 W) drying with 50% (w/w) of water
      according to yields, color (L*, a*, b*) values and sensory properties (color,
      odor, general appearance). For packed bed drying at 60  degrees C yields were
      54.28 +/- 3.78, 47.70 +/- 1.73 and 52.57 +/- 7.04% for 0, 25 and 50% bulgur flour
      containing samples, respectively. Lightness (L*) values of couscous-like samples
      were decreased with increasing the quantity of bulgur flour after both drying
      processes. Results of sensory analysis revealed that couscous-like bulgur were
      more preferable for consumers.

PMID- 29184253
TI  - Malt sprout, an underused beer by-product with promising potential for the growth
      and dehydration of lactobacilli strains.
AB  - Malt sprout (MS), a by-product of the malt industry obtained by removing rootlets
      and sprouts from the seed of germinated barley (Hordeum vulgare L.), was used as
      culture, dehydration and storage medium of three strains of lactobacilli:
      Lactobacillus salivarius CM-CIDCA 1231B and CM-CIDCA 1232Y and Lactobacillus
      plantarum CIDCA 83114. The three strains were grown in MS and MS supplemented
      with 20% w/v fructo-oligosaccharides (MS FOS). Bacterial growth was determined by
      registering the decrease of pH and by plate counting. Comparable results with
      those of microorganisms grown in MRS (controls) were observed in terms of lag
      times, DeltapH and acidification rates. Furthermore, during fermentation, a
      significant increase of DP6 (FOS with degree of polymerization 6) was observed at
      expenses of inulin and DP7, probably indicating their hydrolysis. A concomitant
      decrease of DP3, sucrose and monosaccharides was also observed, as result of
      their bacterial consumption during growth. The presence of FOS in the fermented
      media protected microorganisms during freeze-drying and storage, as no decrease
      of culturability was observed after 60 days at 4  degrees C (> 108 CFU/mL). Using
      MS appears as an innovative strategy for the production of lactobacilli at large
      scale, supporting their use for the elaboration of functional foods containing
      prebiotics and probiotics.

PMID- 29184254
TI  - Characterization of probiotic potential of Bacillus species isolated from a
      traditional brine pickle.
AB  - Fermented foods are known for their potential as main source of probiotics. The
      present study aimed at investigating the probiotic properties of bacteria
      isolated from fermented mango pickle. Non-hemolytic fermenting microbiota
      isolated from mango pickle was screened in vitro for their basic probiotic
      properties such as acid tolerance, bile salt, lysozyme and salt tolerance. They
      were also tested for their beneficial characters like cholesterol removal,
      bacterial adhesion to hydrocarbons, auto-aggregation, antimicrobial activity,
      beta-galactosidase activity, exopolysaccharide production and adhesion to HT-29
      cell line. Outputs of these parameters were subjected to principal component
      analysis (PCA) and these results were interpreted to select prospective bacterial
      isolates that can be used as potential probiotics. Out of eight isolates,
      PUFSTP35 (Bacillus licheniformis), PUFSTP38 (Bacillus amyloliquefaciens) and
      PUFSTP39 (Bacillus subtilis) showed similar trend to Weissella cibaria (MTCC
      9814) that was used as a reference strain for profiling probiotic properties. B.
      licheniformis PUFSTP35 from fermented mango pickle appear to be the most
      potential candidate for use as a beneficial probiotic.

PMID- 29184255
TI  - Physicochemical, morphological, thermal and pasting characteristics of starches
      from moth bean (Vigna aconitifolia) cultivars grown in India: an underutilized
      crop.
AB  - This is a first kind of study on genotype diversity of starches of Moth Bean an
      underutilized pulse of India. Physicochemical properties like amylose content
      (7.8-21.4%), swelling power (11-13.5 g/g), solubility (5.9-9.0%) of starches were
      observed to differ significantly among the six moth bean starches. Swelling power
      of all the moth bean starches was observed to increase in the temperature range
      of 55-95  degrees C. Scanning electron microscopy indicated polyhedral, irregular
      shape of granule. X-ray diffraction studies indicated a 'C' type crystalline
      structure and the starches differed significantly in relative crystallinity (17
      34%) which affected significantly retro gradation tendencies of the starches.
      Peak viscosity of starches varied significantly and ranged between 4580 and 5087
      cP. Resistant starch content of starches also varied significantly among the
      cultivars and ranged between 57.3 and 75.6%.

PMID- 29184256
TI  - Factors influencing anthocyanin loss during nixtamalization of blue purple maize
      grain.
AB  - Blue purple maize grain loses a great amount of anthocyanins during the
      nixtamalization processing. The impact of the process factors on anthocyanins
      losses has not been studied in detail. The objectives of this work were to: (1)
      determine the step of the nixtamalization procedure where the greatest
      anthocyanin loss occurs and (2) study the effect of cooking time, alkali
      concentration, and sample size on anthocyanin losses (AL), and on the color of
      masa and tortilla from blue purple maize grain. Two cooking times were assayed
      (25 and 35 min), three alkali concentrations (0.5, 0.7, and 1.0% w/w), and two
      maize grain sample sizes (100 and 1000 g). Alkali concentration determines the
      time required to solubilize the maize grain pericarp, higher concentrations
      resulted in shorter maize grain pericarp solubilization times and this variable
      was related with AL. The greatest AL occurred during the grain cooking step, but
      an additional loss took place during the steeping of cooked grain. For the
      cooking time of 25 min, AL were of 38.3% during the cooking step, and 21.3%
      during the steeping of cooked grain. The cooking time had no effect (p > 0.05) on
      AL in masa and tortilla whereas alkali concentration and sample size
      significantly affected it. The greater the concentration and size, the higher the
      AL. The color of masa and tortilla were affected by cooking time and alkali
      concentration. Increasing alkali concentration during the nixtamalization
      procedure, reduced the brightness and chroma of masa and tortilla and made these
      products seem darker and dull.

PMID- 29184257
TI  - Optimization and characterization of high pressure homogenization produced
      chemically modified starch nanoparticles.
AB  - Chemically modified starch (RS4) nanoparticles were synthesized through
      homogenization and water-in-oil mini-emulsion cross-linking. Homogenization was
      optimized with regard to z-average diameter by using a three-factor-three-level
      Box-Behnken design. Homogenization pressure (X1), oil/water ratio (X2), and
      surfactant (X3) were selected as independent variables, whereas z-average
      diameter was considered as a dependent variable. The following optimum
      preparation conditions were obtained to achieve the minimum average size of these
      nanoparticles: 50 MPa homogenization pressure, 10:1 oil/water ratio, and 2 g
      surfactant amount, when the predicted z-average diameter was 303.6 nm. The
      physicochemical properties of these nanoparticles were also determined. Dynamic
      light scattering experiments revealed that RS4 nanoparticles measuring a PdI of
      0.380 and an average size of approximately 300 nm, which was very close to the
      predicted z-average diameter (303.6 nm). The absolute value of zeta potential of
      RS4 nanoparticles (39.7 mV) was higher than RS4 (32.4 mV), with strengthened
      swelling power. X-ray diffraction results revealed that homogenization induced a
      disruption in crystalline structure of RS4 nanoparticles led to amorphous or low
      crystallinity. Results of stability analysis showed that RS4 nanosuspensions
      (particle size) had good stability at 30  degrees C over 24 h.

PMID- 29184258
TI  - Effect of mass on convective heat transfer coefficient during open sun drying of
      groundnut.
AB  - In this work, an attempt is made to study the effect of mass on convective heat
      transfer coefficient (CHTC) for open sun drying (OSD) of groundnut (Arachis
      hypogaea L.). Experiments were conducted during the month of May, 2016 in the
      climatic condition of Rohtak, India (28 degrees 54'0"N 76 degrees 34'0"E).
      Groundnut samples of 130 and 198 g were dried under OSD condition till almost no
      variation in its mass was recorded. Hourly data of the mass evaporated, groundnut
      temperature, relative humidity and ambient temperature were recorded. The
      experimental data obtained were used to determine the constants 'C' and 'n' in
      the Nusselt number expression using linear regression method. CHTC increased with
      the increase in mass of groundnuts. The experimental errors in terms of percent
      uncertainty were found to vary from 44.29 to 48.77%.

PMID- 29184259
TI  - Isolated Peritoneal, Mesenteric, and Omental Hydatid Cyst: A Clinicopathologic
      Narrative Review.
AB  - Hydatid disease (HD) is caused by Echinococcus granulosus and is endemic in many
      parts of the world. This parasitic tapeworm can produce cysts in almost every
      organ of the body, with the liver and lung being the most frequently targeted
      organs. Peritoneum, omentum, and mesentery are among these unusual locations,
      which can cause diagnostic challenge and treatment delay. This review provides
      information on the reported cases of the peritoneal, omental, and mesenteric
      hydatid cyst in the world during the last 20 years. During the last 20 years,
      there have been 49 published cases of hydatid cysts in the peritoneum, mesentery,
      and omentum. Among the reported cases in the English literature, the most common
      presenting symptom has been chronic abdominal pain and the method of primary
      diagnosis has been ELISA and ultrasonography. The best treatment modalities have
      been surgical excision, with and without adjuvant therapy, with albendazole and
      scolicidal agents. The published follow-up studies showed a low recurrence rate.

PMID- 29184260
TI  - Topical Effects of Artemisia Absinthium Ointment and Liniment in Comparison with
      Piroxicam Gel in Patients with Knee Joint Osteoarthritis: A Randomized Double
      Blind Controlled Trial.
AB  - Background: Pain alleviation and improvement of functional status are the main
      objectives in the treatment of osteoarthritis. Artemisia absinthium (AA) was used
      traditionally in reducing pain and inflammation. The aim of the present study was
      to compare the effects of topical formulations of AA and piroxicam gel (PG) among
      patients with knee osteoarthritis. Methods: In total, 90 outpatients aged 30-70
      years with the diagnosis of primary osteoarthritis in at least one knee were
      enrolled in a randomized double-blind clinical trial. The patients referred to
      the Rheumatology Clinic at Shahid Beheshti Hospital in Hamadan province during
      2012-2013. The patients were randomly assigned into three groups, 30 patients per
      group, and respectively received AA ointment (AAO) 3%, AA liniment (AAL) 3%, and
      PG; three times daily (TID) for 4 weeks. The patients were visited at baseline,
      week 4, and week 6. The effectiveness criteria were pain severity which was
      assessed with a 10-point visual analog scale (VAS), the Western Ontario and
      McMaster Universities osteoarthritis index (WOMAC) for total pain score (WTPS),
      total physical function score (WTPFS), and total stiffness score (WTSS). Repeated
      measure ANOVA, paired t test and post hoc were used to compare variables.
      Statistical analysis was performed using the SPSS software, version 13.0 (SPSS
      Inc., Chicago, Illinois). Results: All groups had similar patient demographics.
      The administration of PG significantly improved all tested criteria with no
      recurrence after discontinuing the treatment protocol. AAO alleviated all tested
      factors except for WTSS. Alleviation was comparable to PG. AAL only reduced pain
      factors (VAS, WTPS) in week 4 with recurrence in week 6. Conclusion:
      Administration of Artemisia ointment may have beneficial effects in the treatment
      of osteoarthritis. Trial Registration Number: IRCT201202123109N3.

PMID- 29184261
TI  - Adherence to the CONSORT Statement in the Reporting of Randomized Controlled
      Trials on Pharmacological Interventions Published in Iranian Medical Journals.
AB  - Background: Among manuscripts submitted to biomedical journals, randomized
      controlled trials (RCTs) form the backbone of evidence-based medicine. Hence,
      their protocol should be designed rigorously and their results should be reported
      clearly. To improve the quality of RCT reporting, researchers developed the
      CONSORT Statement in 1996 and updated it in 2010. This study was designed to
      assess the quality of RCT reporting vis-a-vis adherence to CONSORT among articles
      published in Iranian medical journals (English, Persian, CONSORT-endorsing, and
      non-CONSORT-endorsing). Methods: In this cross-sectional study, all RCTs
      published in all Iranian medical journals from September 2012 to September 2013
      were retrieved to evaluate their adherence to CONSORT. The journals' instructions
      for authors were also reviewed to find out whether or not they endorsed CONSORT.
      The CONSORT 2010 Checklist was used. Microsoft Excel 2007 was applied to analyze
      the data, and MedCalc was employed to compare the groups. Results: Totally, 492
      pharmacological RCTs that met our inclusion criteria were identified. Twenty-five
      items were reported in fewer than 50% of the articles. The differences between
      the articles published in Persian and English language journals were
      statistically significant in 17 items. The differences between the articles
      published in the CONSORT-endorsing and non-CONSORT-endorsing journals were
      significant in 8 items. Conclusion: Our findings showed very weak adherence to
      CONSORT. Authors, reviewers, and editors should be trained to use standards
      expressed by the CONSORT Group in reporting RCTs.

PMID- 29184262
TI  - Cerebral Ischemia-Reperfusion Injuries in Vanadyl-Treated Diabetic Rats.
AB  - Background: Ischemic stroke recovery is poor in diabetic mellitus (DM). Vanadium
      compounds (vanadium) relieve DM signs, but their influences on cerebral
      ischemia/reperfusion injury (I/RI) are inconclusive. Herein, the intensity of
      I/RI was inspected in vanadium-treated DM rats. Methods: Rats made diabetic with
      a single intravenous dose of streptozocin (39 mg/kg). Normal and DM rats used
      water or vanadyl solution for 45 days. Under isoflurane anesthesia, right middle
      cerebral artery occlusion was performed for 60 minutes and 12 hours reperfusion.
      Ischemic rats were divided into untreated-control normal (ICN) and diabetic
      (ICD), vanadium-treated normal (IVTN) and diabetic (IVTD) groups (n=14 each).
      After neurological deficit score (NDS) test, the rats were sacrificed and their
      brain removed and stained with triphenyltetrazolium chloride (TTC) to measure
      cerebral infarct volume (CIV, mm3) or Evans blue extravasation (EBE, MUg/g wet
      tissue). Data analysis was performed using one-way ANOVA and Tukey's test (SPSS
      software, version 21.0) and P values <0.05 were considered statistically
      significant. Results: Blood glucose (BG, mg/dL) was similar in ICN and IVTN,
      elevated in IVTD and ICD (245+/-6 vs. 344+/-2, P<0.001). The increased CIV in ICN
      and IVTN was similar (48+/-2 and 34+/-5), very high in ICD but lower in IVTD
      (249+/-37 vs. 110+/-16, P<0.001). EBE was absent in non-lesioned hemispheres,
      similarly increased in lesioned hemispheres of ICN and IVTN (14+/-1 and 13+/-1).
      EBE in IVTD was significantly lower than ICD (21+/-2 vs. 33+/-5, P=0.01).
      Conclusion: I/RI was moderate in normoglycemia and did not change with vanadium.
      Hyperglycemia robustly intensified I/RI. Vanadium ameliorated hyperglycemia and
      reduced I/RI. Nonetheless, more investigations are required to link the
      mechanisms of vanadium on DM and stroke injuries.

PMID- 29184263
TI  - Antidiabetic and Antidyslipidemic Activities of the Aqueous Extract of
      Cochlospermum planchonii Leaves in Streptozotocin-Induced Diabetic Rats.
AB  - Background: Diabetes mellitus is considered one of the 5 principal causes of
      death in the world and is recognized as a global public health issue because of
      its multifactorial facets affecting essential biochemical processes in the body.
      This study investigated the antidiabetic and antidyslipidemic activities of the
      aqueous extract of Cochlospermum planchonii (C. planchonii) leaves in
      streptozotocin (STZ)-induced diabetic rats. Methods: Thirty adult female rats
      (Rattus norvegicus) weighing 153+/-3.41g were randomized into 6 groups of 5
      animals each. STZ-induced diabetic rats were orally administered 50, 100, and 200
      mg/kg body weight of the extract, respectively, once a day, and their blood
      glucose levels as well as variations of diabetes-associated biomarkers including
      alpha amylase, glucose-6-phosphate dehydrogenase (G6PDH), and lipid profile by
      the extract were monitored for 21 days. The results were expressed as means+/
      SEMs and compared with repeated measures using SPSS, Data Editor, version 16.0.
      Results: The aqueous extract of C. planchonii leaves significantly reduced the
      blood glucose level in a dose-dependent manner, with the highest dose producing a
      74.52% reduction after 21 days of administration, which compared significantly
      (P<0.01) with the control and metformin-treated groups. Similarly, STZ-induced
      diabetic mediated alterations in the serum lipids were significantly (P<0.01)
      restored by the extract. In addition, the aqueous extract of C. planchonii leaves
      significantly attenuated the decrease in the activity of G6PDH and the increase
      in the activity of alpha-AMY in the liver of the STZ-induced diabetic rats.
      Conclusions: Overall, the aqueous extract of C. planchonii leaves could be used
      to manage diabetes and other related complications.

PMID- 29184264
TI  - Effects of Subacute Administration of Co-Trimoxazole and Folic Acid on Ovarian
      Tissue in Adult Female Rats.
AB  - Background: Previous studies have reported the antifertility activities of
      sulfonamides. This study was designed to evaluate the effects of co-trimoxazole
      and its co-administration with folic acid on ovarian tissue in female rats.
      Methods: A total of 54 rats were randomly divided into 9 groups (n=6). Group I
      served as the control and group II (vehicle) received saline. Other groups, III
      to IX, received co-trimoxazole (30, 60, and 120 mg/kg; i.p.), folic acid (1
      mg/kg; i.p.) or their combination for 14 days, respectively. The oocytes were
      obtained from each group at the end of the 14th days and scored for maturational
      status as germinal vesicle (GV), metaphase I (MI), or metaphase II (MII). The
      number of primordial follicle (PrF), primary follicle (PF), and secondary
      follicle in formalin-fixed ovaries were counted under light microscopy. The data
      were analyzed by one-way ANOVA followed by post-hoc Dunnet test using SPSS
      statistical software (version 17.0). Results were considered statistically
      significant at P<0.05. Results: Co-trimoxazole (60 and 120 mg/kg) treatment for
      14 days caused a significant decrease in the number of GV (P=0.02, P<0.001), MI
      and MII (P=0.03, P<0.001), a significant increase in structural abnormalities,
      including PrF, PF and secondary follicle (P<0.001) as well as congestion,
      inflammation and necrosis of ovarian tissue compared to the vehicle group. Folic
      acid co-administration with co-trimoxazole reversed partially all these
      parameters compared to the co-trimoxazole group (P<0.001). Conclusion: The data
      showed the adverse effects of co-trimoxazole on the ovarian maturational status
      and tissue structure which was reversed partially by folic acid co-administration
      in rats.

PMID- 29184265
TI  - Long-term Low-Intensity Endurance Exercise along with Blood-Flow Restriction
      Improves Muscle Mass and Neuromuscular Junction Compartments in Old Rats.
AB  - Background: During the aging process, muscle atrophy and neuromuscular junction
      remodeling are inevitable. The present study aimed to clarify whether low
      intensity aerobic exercise along with limb blood-flow restriction (BFR) could
      improve aging-induced muscle atrophy and nicotinic acetylcholine receptors
      (nAChRs) at the neuromuscular junction. Methods: Forty-eight male Wistar rats,
      aged 23-24 months, were randomly divided into control, sham (Sh: subjected to
      surgery without BFR), BFR (subjected to BFR), exercise (Ex: subjected to 10 weeks
      of low-intensity exercise), Sh+Ex, and BFR+Ex groups. Forty-eight hours after the
      last training session, the animals were sacrificed and their soleus and extensor
      digitorum longus (EDL) muscles were removed. The hypertrophy index was
      calculated, and molecular parameters were measured using western blotting.
      Statistical analysis was done with ANOVA using SPSS (version 20), with a P<0.05
      as the level of significance. Results: The control and Sh groups showed weight
      gain (P=0.001), whereas the Ex, Sh+Ex, and BFR+Ex groups had significant weight
      loss (P<0.001). The hypertrophy index of the soleus was significantly higher in
      the BFR+Ex group than in the control, Sh, and BFR groups (P<0.001). BFR+Ex
      induced significant hypertrophic effects on the EDL (P<0.001 vs. the control, Sh,
      Ex, and Sh+Ex groups, and P=0.006 vs. the BFR group). BFR+Ex also increased
      nAChRs in the soleus (P=0.02 vs. the control and Sh groups) and the EDL (P=0.008
      vs. the control and Sh groups). Conclusion: BFR plus mild exercise is a safe
      method with potential beneficial effects in protecting and augmenting muscle mass
      and nAChR clustering at the neuromuscular junction in old rats.

PMID- 29184266
TI  - Effects of Saponin from Trigonella Foenum-Graecum Seeds on Dyslipidemia.
AB  - Background: Saponins identified from fenugreek (Trigonella foenum-graecum) seeds
      are reported effective on dyslipidemia. However, the definite mechanism is still
      not elucidated systematically. In this study, we evaluate the effects of saponin
      extract on cholesterol absorption, metabolism, synthesis, and reverse cholesterol
      transport in vivo. Methods: Saponin extract was prepared according to a craft
      established in our previous study. After the establishment of dyslipidemia model,
      40 male Sprague-Dawley rats were divided into five groups, namely the control
      group (normal diet plus normal saline), HFD group (high fat diet plus normal
      saline), Lipitor group (high fat diet plus Lipitor (2 mg/kg)), and L, M, and H
      saponin groups (high fat diet plus saponin in dosages of 6, 12, and 24 mg/kg,
      respectively). Rats were sacrificed at the end of the 9th week after treatment.
      Biochemical characteristics of rats were tested, histopathological sections of
      liver tissue were observed, and the protein and mRNA expression of related
      factors of cholesterol in the intestine and liver were determined. One-way ANOVA
      test (SPSS software version 11.5, Chicago, IL, USA) was used to determine
      statistically significant differences between the HFD and other groups. Results:
      In saponin groups, the serum lipid, bile acid efflux, anti-peroxide activities,
      and lipid area of liver tissue improved. Cholesterol 7alpha-hydroxylase and
      scavenger receptor class B type I elevated in the liver. 3-hydroxy-3
      methylglutaryl coenzyme A reductase levels were suppressed in both the serum and
      liver. However, significant cholesterol efflux was not found and Niemann-Pick C1
      Like 1 levels elevated in the intestine. Conclusion: The mechanisms of saponin in
      Fenugreek effect on ameliorating dyslipidemia are probably related to accelerated
      cholesterol metabolism, inhibited cholesterol synthesis, and facilitated reverse
      cholesterol transport, but not cholesterol absorption.

PMID- 29184267
TI  - Deltamethrin-Induced Hepatotoxicity and Virgin Olive Oil Consumption: An
      Experimental Study.
AB  - Background: Deltamethrin (DM) is a synthetic pyrethroid insecticide which can
      lead to pathological effects in mammals through oxidative stress. On the other
      hand, virgin olive oil (VOO) is a rich source of phenolic compounds with
      antioxidants. The aim of the present study was to determine the protective
      effects of VOO against DM-induced hepatotoxicity. Methods: Thirty-six mice were
      randomly separated into 4 groups: vehicle group, VOO group, DM group, and DM plus
      VOO group. Immunohistochemistry of PARP, COX-2, and caspase-3 with the
      biochemical analysis of malondialdehyde and total antioxidant capacity levels
      were performed in the liver samples 5 weeks after gavaging. Statistical analysis
      was performed using SPSS, version 15. The data were compared between the groups
      using the Tukey multiple comparison tests and the analysis of the variance. A P
      value <0.05 was considered significant. Results: The malondialdehyde level in the
      liver was increased in the DM group (71.18+/-0.01), whereas it was significantly
      (P=0.001) decreased after VOO administration in the DM plus VOO group (39.59+/
      2.43). While the total antioxidant capacity level in the liver was decreased in
      the DM group (3.05+/-0.05), it was significantly increased (P=0.03) after VOO
      administration in the DM plus VOO group (3.95+/-0.04). A greater expression of
      caspase-3 (P=0.008), COX-2 (P =0.004), and PARP (P 0.006) could be detected in
      the DM group, while it was significantly (P=0.009) attenuated in the DM plus VOO
      group. Also, the degeneration of hepatocytes, which was detected in the DM group,
      was attenuated after VOO consumption. Conclusions: VOO exerted protective effects
      against DM-induced hepatotoxicity, which might be associated with its anti
      apoptotic, anti-inflammatory, and antioxidative properties.

PMID- 29184268
TI  - Impacts of Bone Marrow Stem Cells on Caspase-3 Levels after Spinal Cord Injury in
      Mice.
AB  - Spinal cord injury (SCI) is a drastic disability that leads to spinal cord
      impairment. This study sought to determine the effects of bone marrow stem cells
      (BMSCs) on caspase-3 levels after acute SCI in mice. Forty-two mice were randomly
      divided into 3 groups: control (2 subcategories), subjected to no intervention;
      sham (3 subcategories), subjected to acute SCI; and experimental (2
      subcategories), subjected to SCI and cell transplantation. In the experimental
      group, 2*105 BMSCs were injected intravenously 1 day after SCI. The mesenchymal
      property of the cells was assessed. The animals in the 3 groups were sacrificed
      1, 21, and 35 days after the induction of injury and caspase-3 levels were
      evaluated using a caspase-3 assay kit. The obtained values were analyzed with
      ANOVA and Tukey tests using GraphPad and SPSS. Based on the assessments, the
      transplanted cells were spindle-shaped and were negative for the hematopoietic
      markers of CD34 and CD45 and positive for the expression of the mesenchymal
      marker of CD90 and osteogenic induction. The caspase-3 levels showed a
      significant increase in the sham and experimental groups in comparison to the
      control group. One day after SCI, the caspase-3 level was significantly higher in
      the sham group (1.157+/-0.117) than in the other groups (P<0.000). Twenty-one
      days after SCI, the caspase-3 level was significantly lower in the experimental
      group than in the sham group (0.4+/-0.095 vs. 0.793+/-0.076; P?0.000). Thirty
      five days following SCI, the caspase-3 level was lower in the experimental group
      than in the sham group (0.223+/-0.027 vs. 0.643+/-0.058; P?0.000). We conclude
      that BMSC transplantation was able to downregulate the caspase-3 level after
      acute SCI, underscoring the role of caspase-3 as a marker for the assessment of
      treatment efficacy in acute SCI.

PMID- 29184269
TI  - Different Presentation of Anomalous Origin of the Left Coronary Artery from the
      Pulmonary Artery in Adults: Case Reports.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital cardiac malformation. We report three cases of ALCAPA who
      survived to adulthood. The first case was a 51-year-old woman who complained of
      typical chest pain that was diagnosed with ALCAPA using cardiac catheterization
      and coronary computed tomographic angiography (CTA). The second case was a 30
      year-old woman with a history of surgery for atrial septal defect at 10 years old
      who presented with progressive exertional dyspnea. Cardiac catheterization
      confirmed the diagnosis of ALCAPA. The third case was a 19-year-old man who was
      brought to our clinic due to aborted sudden cardiac death on the previous day.
      Cardiac catheterization and coronary CTA confirmed the diagnosis. They underwent
      the closure of orifice of the anomalous left coronary artery and grafting the
      left anterior descending artery concomitantly with mitral valve repair. All
      patients were followed up during a mean of 8.7 months and they were asymptomatic.

PMID- 29184270
TI  - Recurrent Psammomatoid Juvenile Ossifying Fibroma with Aneurysmal Bone Cyst: An
      Unusual Case Presentation.
AB  - Juvenile ossifying fibroma (JOF) is a rare, benign, locally aggressive entity of
      the extragnathic craniofacial bones with a high tendency towards recurrence. Two
      distinctive microscopic patterns of juvenile ossifying fibroma have been
      described: a trabecular juvenile ossifying fibroma (TrJOF) and a psammomatoid
      juvenile ossifying fibroma (PJOF). Psammomatoid variant is predominantly a
      craniofacial lesion and occurs rarely in the jaws. The pathognomonic
      histopathologic feature is the presence of spherical ossicles, which are similar
      to psammoma bodies. Aneurysmal bone cyst exists as a secondary lesion arising
      from another osseous condition such as fibrous dysplasia, ossifying fibroma and
      giant cell granuloma. Very few cases of juvenile psammomatoid ossifying fibroma
      in association with the secondary aneurysmal bone cyst formation have been
      reported in the literature. Treatment consists of complete surgical removal; the
      incomplete excision has been associated with a high local recurrence rate. The
      authors report a case of recurrence of psammomatoid juvenile ossifying fibroma
      with aneurysmal bone cyst in an 8-year-old boy emphasizing the point that
      concomitant occurrence of these locally aggressive lesions requires adequate
      surgical removal and long-term follow-up.

PMID- 29184271
TI  - A Case of Cushing's Syndrome in Pregnancy.
AB  - Cushing's syndrome (CS) occurs rarely during pregnancy. CS can be caused by
      prolonged abnormal exposure to excess glucocorticoids leading to special and
      significant signs and symptoms. It is often difficult to diagnose pathological
      hypercortisolism in pregnant women since some symptoms of the disease might be
      due to a complicated pregnancy, including preeclampsia or gestational diabetes.
      In this study, we report the case of a 29-year-old female who referred to our
      institution with hypertension, weakness, steria, and truncal obesity. Physical
      examination revealed cushingoid characteristic. She was also found to be 27 weeks
      pregnant. CS was diagnosed on the basis of abnormal serum cortisol and
      adrenocorticotropin hormone (ACTH) levels, as well as radiologic findings. She
      eventually gave birth to a preterm infant via vaginal delivery. A right adrenal
      adenoma was diagnosed and was subsequently treated with surgical resection. The
      patient's condition remained stable after the surgery.

PMID- 29184272
TI  - Approach to Chronic Secondary Headache: A Case Report on Unusual Drug Side
      Effects.
AB  - In this article, we present the case of a 12-year-old female child who complained
      of bilateral temporal and frontal headache for 2 to 3 months with nausea and
      vomiting. Physical examination revealed right-sided sixth cranial nerve palsy and
      papilledema in ophthalmoscopy. To find the cause of increased intracranial
      pressure, the patient underwent brain imaging and brain MRI showed no
      abnormality. Ultimately, lumbar puncture (LP) was performed and cerebrospinal
      fluid (CSF) pressure was 280 mmH2O with normal chemistry. We considered
      pseudotumor cerebri as the first diagnosis. LP was carried out three times and
      30cc of CSF was tapped each time. Finally, patient's headache and papilledema
      improved and physical examination after 6 months showed no sign of raised
      intracranial pressure (rICP). The most prominent point in her past medical
      history was the use of growth hormone (GH) for 2 years. No sign of symptom
      relapse has been seen after 6 months of drug discontinuation. We must consider
      the hazard of growth hormone as a potential cause of increased intracranial
      pressure. When the use of GH is justified, the follow-up must include an
      ophthalmoscopy examination in each session.

PMID- 29184273
TI  - Elderly-customized hatha yoga effects on the vascular inflammation factors of
      elderly women.
AB  - [Purpose] The aim of this study was to examine the effects of the application of
      elderly-customized hatha yoga on the vascular inflammation factors of elderly
      women. [Subjects and Methods] This research was conducted with 14 elderly women,
      between 70 and 80 years old, divided into an elderly-customized hatha yoga group
      (n=7) and a control group (n=7). The application group participated in a hatha
      yoga program designed to be elderly-friendly for 10 weeks. At the end of the
      program, the vascular inflammation factors were measured, including the albumin,
      white blood cell count, fibrinogen, high sensitivity C-reactive protein (hs-CRP),
      and erythrocyte sedimentation rate (ESR). [Results] In the hatha yoga group, the
      albumin increased significantly after the application, when compared to the level
      before the application, while the fibrinogen, hs-CRP, and ESR decreased
      significantly. In the control group, the vascular inflammation factor levels
      before and after the application period were not significantly different.
      [Conclusion] Based on the results of this study, the application of elderly
      customized hatha yoga created positive changes in the vascular inflammation
      factors of elderly women.

PMID- 29184274
TI  - The relationship between physical capacity and fear avoidance beliefs in patients
      with chronic low back pain.
AB  - [Purpose] The aim of this study was to investigate the relationship between
      physical capacity and fear avoidance beliefs in patients with chronic low back
      pain. [Subjects and Methods] This cross sectional study included 131 male
      university students with chronic low back pain. All the patients completed a fear
      avoidance beliefs questionnaire. Each participant performed a physical capacity
      test, which included hand grip force, leg strength, abdominal muscle endurance,
      flexibility, and cardiopulmonary endurance testing. [Results] Negative
      correlation was observed between physical capacity (leg strength, abdominal
      muscle endurance) and fear avoidance beliefs regarding work. Physical capacity
      (hand grip force, leg strength, cardiopulmonary endurance) showed a negative
      correlation with fear avoidance beliefs about physical activity. Abdominal muscle
      endurance and cardiopulmonary endurance were predictors of fear avoidance
      beliefs. [Conclusion] Physical capacity showed a negative correlation with fear
      avoidance beliefs in patients with chronic low back pain. The results of this
      study suggest that physical capacity is an important factor for predicting fear
      avoidance beliefs in patients with chronic low back pain.

PMID- 29184275
TI  - Effects of lower extremity injuries on aerobic exercise capacity, anaerobic
      power, and knee isokinetic muscular function in high school soccer players.
AB  - [Purpose] The study investigated the effects of lower extremity injuries on
      aerobic exercise capacity, anaerobic power, and knee isokinetic muscular function
      in high school soccer players. [Subjects and Methods] The study assessed U High
      School soccer players (n=40) in S area, South Korea, divided into 2 groups: a
      lower extremity injury group (n=16) comprising those with knee and ankle injuries
      and a control group (n=24) without injury. Aerobic exercise capacity, anaerobic
      power, and knee isokinetic muscular function were compared and analyzed.
      [Results] Regarding the aerobic exercise capacity test, significant differences
      were observed in maximal oxygen uptake and anaerobic threshold between both
      groups. For the anaerobic power test, no significant difference was observed in
      peak power and average power between the groups; however, a significant
      difference in fatigue index was noted. Regarding the knee isokinetic muscular
      test, no significant difference was noted in knee flexion, extension, and
      flexion/extension ratio between both groups. [Conclusion] Lower extremity injury
      was associated with reduced aerobic exercise capacity and a higher fatigue index
      with respect to anaerobic exercise capacity. Therefore, it seems necessary to
      establish post-injury training programs that improve aerobic and anaerobic
      exercise capacity for soccer players who experience lower extremity injury.

PMID- 29184276
TI  - Comparison of the effects of visual feedback training and unstable surface
      training on static and dynamic balance in patients with stroke.
AB  - [Purpose] This study compared the effects of visual feedback training and
      unstable surface training on the static and dynamic balance of stroke patients.
      [Subjects and Methods] The study enrolled 20 stroke patients and randomly
      assigned them to visual feedback training and unstable surface training groups.
      Both groups performed 30 minutes of conventional exercise therapy twice a week
      for 4 weeks. In addition, the subjects in the visual feedback training group
      completed a visual feedback training regimen and the subjects in the unstable
      surface training group completed training on an unstable surface (30-minute
      session three times a week for 4 weeks in both groups). Static and dynamic
      balance parameters were recorded immediately before and after the 4 weeks of
      training. For data analysis, the paired and independent t-test was used to
      compare the two groups. [Results] In the visual feedback training group, the sway
      line at the postural sway of the center of pressure and trace length decreased
      significantly after training. In both groups, the sway range at the limits of
      stability in the anteroposterior and mediolateral directions increased
      significantly after training. [Conclusion] Visual feedback training was better at
      improving static and dynamic balance than unstable surface training in stroke
      patients.

PMID- 29184277
TI  - Effect of axial shoulder external rotation exercise in side-lying using visual
      feedback on shoulder external rotators.
AB  - [Purpose] This study aimed to determine effectiveness of axial side-lying wiper
      exercise using the visual feedback with a laser pointer on infraspinatus and
      posterior deltoid muscles. [Subjects and Methods] The subjects were 22 healthy
      adults (18 males, 4 females) in their 20s who consented to participate in the
      present study. Surface Electromyography was used to measure the infraspinatus and
      posterior deltoid muscle activity before and after an intervention. The
      intervention consisted of performing side-lying wiper exercise with a 1-kg
      dumbbell and a ruled paper for 30 minutes. [Results] The infraspinatus
      illustrated significantly increased muscle activity after intervention. The
      posterior deltoid also showed increased activity after intervention but it was
      not significant. [Conclusion] Axial side-lying wiper exercise using the visual
      feedback has the therapeutic effectiveness for the selective infraspinatus muscle
      strengthening. Therefore it can be useful to provide shoulder movements with
      stability.

PMID- 29184278
TI  - Reliability of the test of gross motor development second edition (TGMD-2) for
      Kindergarten children in Myanmar.
AB  - [Purpose] The purpose of this study was to investigate reliability of the test of
      gross motor development second edition (TGMD-2) for Kindergarten children in
      Myanmar. [Subjects and Methods] Fifty healthy Kindergarten children (23 males, 27
      females) whose parents/guardians had given written consent were participated. The
      subjects were explained and demonstrated all 12 gross motor skills of TGMD-2
      before the assessment. Each subject individually performed two trials for each
      gross motor skill and the performance was video recorded. Three raters separately
      watched the video recordings and rated for inter-rater reliability. The second
      assessment was done one month later with 25 out of 50 subjects for test-rest
      reliability. The video recordings of 12 subjects were randomly selected from the
      first 50 recordings for intra-rater reliability six weeks after the first
      assessment. The agreement on the locomotor and object control raw scores and the
      gross motor quotient (GMQ) were calculated. [Results] The findings of all the
      reliability coefficients for the locomotor and object control raw scores and the
      GMQ were interpreted as good and excellent reliability. [Conclusion] The results
      represented that TGMD-2 is a highly reliable and appropriate assessment tool for
      assessing gross motor skill development of Kindergarten children in Myanmar.

PMID- 29184279
TI  - Relationship between gross motor function and the function, activity and
      participation components of the International Classification of Functioning in
      children with spastic cerebral palsy.
AB  - [Purpose] This study aimed to evaluate the relationship between gross motor
      function, measured using the Gross Motor Function Measure (GMFM), Gross Motor
      Function Classification System (GMFCS), Manual Ability Classification System
      (MACS), and Functional Independence Measure for Children (WeeFIM), and Function,
      and Activity and Participation components of the International Classification of
      Functioning, Disability, and Health-Child and Youth Check List (ICF-CY) in
      children with spastic cerebral palsy (CP). [Subjects and Methods] Seventy-seven
      children with spastic CP participated in the study. The GMFM, GMFCS, MACS, and
      WeeFIM were administered in their entirety to patients without orthoses or
      mobility aids. The ICF-CY was used to evaluate the degree of disability and
      health. [Results] The score of the ICF component of Activity and Participation
      had a significantly strong correlation with the scores of GMFM, GMFCS, MACS,
      WeeFIM, and ICF component of Function. [Conclusion] When establishing a treatment
      plan for children with spastic CP, the children's physical abilities, and their
      limitation in activity, performance, and participation, which would be measured
      using the ICF-CY, should be taken into consideration.

PMID- 29184280
TI  - Change in hand dexterity and habitual gait speed reflects cognitive decline over
      time in healthy older adults: a longitudinal study.
AB  - [Purpose] There is a relationship between physical and cognitive functions;
      therefore, impairment of physical function would mean cognitive decline. This
      study aimed to investigate the association between change in physical and
      cognitive functions. [Subjects and Methods] Participants were 169 healthy
      community-dwelling older adults who attend the survey after three years from
      baseline (mean age, 72.4 +/- 4.8 years). Grip strength, one-leg standing balance,
      five-times-sit-to-stand test, timed up and go, 5-m habitual walk, and a peg
      moving task were used to evaluate physical performance. Five cognitive function
      tests were used to assess attention, memory, visuospatial function, verbal
      fluency, and reasoning. Cognitive function was defined as the cumulative score of
      these tests. [Results] At baseline, five-times-sit-to-stand test, timed up and
      go, and hand dexterity were independently associated with cognitive function. In
      longitudinal analyses, changes in habitual walking speed and hand dexterity were
      significantly associated with change in cognitive function. [Conclusion]
      Deterioration of specific physical function, such as hand dexterity and walking
      ability, may be associated with progression of cognitive decline. Decreasing
      extent of daily functions, such as hand dexterity and walking ability, can be
      useful indices to grasp changes in cognitive function.

PMID- 29184281
TI  - High-intensity laser therapy versus pulsed electromagnetic field in the treatment
      of primary dysmenorrhea.
AB  - [Purpose] To determine the efficacy of high intensity laser therapy (HILT) versus
      pulsed electromagnetic field (PEMF) in the treatment of primary dysmenorrhea.
      [Subjects and Methods] This was a randomized clinical trial that included 52
      girls diagnosed with primary dysmenorrhea and who were assigned randomly into two
      groups of equal numbers. The treatment was three sessions every cycle for three
      consecutive cycles where group (A) included those participants treated with HILT
      15 min/session and group (B) those who were treated with PEMF 30 min/session. All
      patients were evaluated before starting the treatment as well as after the end of
      treatment by present pain intensity scale and the prostaglandin level in blood
      and pain relief scale at the end of treatment for both groups. [Results] The
      results showed a significant decrease in the severity of pain, statistically
      significant decrease in prostaglandin level in blood, and a statistically
      significant pain alleviation in both groups. With comparison between both groups
      there was a statistically significant decrease in the severity of pain,
      significant decrease in the blood levels of PGF2alpha, in group (A) than group
      (B). [Conclusion] Both HILT and PEMF are effective in the treatment of primary
      dysmenorrhea with HILT being superior to PEMF.

PMID- 29184282
TI  - Responses of Korean physical therapy students after practice with a virtual
      anatomical system in Japan.
AB  - [Purpose] To investigate responses of Korean physical therapy students, receiving
      medical terminology education in physical therapy both in Korean and English,
      after practice with a virtual anatomical system. [Subjects and Methods] The
      participants were 25 physical therapy students from Konyang University in South
      Korea visiting the International University of Health and Welfare for training
      purposes. The virtual anatomy practice was conducted in English using 3
      dimensional virtual anatomy software constructed using real cadaver photographs.
      A questionnaire about this practice and anatomy was completed after the practice.
      [Results] The results of the questionnaire showed a trend toward high scores for
      virtual anatomy practice. [Conclusion] The present virtual anatomy system was
      created using multi-directional photographs from a real cadaver; therefore, it
      can be used as an auxiliary means of education using cadavers.

PMID- 29184283
TI  - Does treadmill walking with near-infrared light applied to the abdominal area
      reduce local adiposity and body weight?
AB  - [Purpose] The purpose of this study was to determine the effect on local fat
      deposition and body weight of wearing a near-infrared light belt around the
      abdomen. [Subjects and Methods] Twenty-eight obese female subjects participated
      in this experiment. For measurement of body composition, an impedance-style body
      fat analyzer was used. The experimental group performed treadmill walking 3 times
      per week for 12 weeks while wearing an activated near-infrared belt around the
      abdomen. The near-infrared belt was composed of light-emitting diodes having
      wavelengths of 630 nm, 830 nm, 880 nm, and 956 nm. [Results] The analysis of
      abdominal circumference indicated that the abdominal circumference of the
      experimental group was reduced in post-test measurements compared to pre-test.
      [Conclusion] This investigation showed significant reductions in abdominal
      circumference, abdominal fat percentage, fat mass, and body-mass index for the
      experimental compared to the control group, suggesting that changes in body
      composition can be enhanced when near-infrared radiation is applied to the
      abdomen during walking.

PMID- 29184284
TI  - The effects of short-term lumbar stability cross taping on muscle strength of
      trunk extension and lumbar pain level in patients with chronic back.
AB  - [Purpose] The purpose of this study was to investigate the effects of short-term
      lumbar stability cross taping program on muscle strength of trunk extension and
      lumbar pain level in patients with chronic back pain. [Subjects and Methods] The
      present study divided 14 patients with chronic back pain into the stability cross
      taping group (SCTG; n=7) and the control group (CONG; n=7). Lumbar cross taping
      was applied to SCTG for 7 days, but the taping was not applied to CONG. After 7
      days of the lumbar stability cross taping application to SCTG, lumbar muscle
      function and lumbar pain levels were measured using a Medx lumbar extension
      machine (Medx, USA) and a visual analogue scale (VAS) for the subjects in both
      SCTG and CONG. [Results] For SCTG, all the elements in lumbar muscle function and
      were significantly improved and lumbar pain level was also significantly reduced
      after the application of the 7-day lumbar stability cross taping. However, CONG
      did not show any statistically significant changes. [Conclusion] The results of
      the present study showed that the lumbar stability cross taping is an effective
      rehabilitation to improve lumbar muscle function and reduce lumbar pain level in
      patients with chronic back pain.

PMID- 29184285
TI  - Knee position sense: does the time interval at the target angle affect position
      accuracy?
AB  - [Purpose] This study examined whether the interval at the target angle during
      knee joint position sense (JPS) affected reposition accuracy, and evaluated the
      consequence of this factor on test-retest reliability. [Subjects and Methods]
      Twenty healthy subjects participated in this study. Reposition ability was
      measured after the knee was placed at a target angle (ranging from 40 degrees  to
      60 degrees ) for intervals of 3, 6, 9, and 12 seconds, in randomized order. Two
      trials were performed for each condition. The measurement was repeated after a
      week. The absolute error (AE) of each trial and average AE under each condition
      within the two measures were used for data analysis. [Results] No significant
      difference was found in comparing the AE or the average AE during all trials and
      between the two measures. Fair-to-good reliability was found for the AE results
      of all trials under the conditions of 3, 6, and 12 seconds. Poor reliability was
      found with time interval of 9 seconds. [Conclusion] The length of time needed to
      memorize the target angle during knee JPS test might affect test reliability.
      Practitioners can use this information when collecting JPS data.

PMID- 29184286
TI  - Test-retest reliability of linear and nonlinear measures of postural stability
      during visual deprivation in healthy subjects.
AB  - [Purpose] The purpose of this study is to evaluate the reliability of linear and
      nonlinear measures of the center of pressure (COP) during visual deprivation.
      [Subjects and Methods] Fifteen young adults participated in this study. COP
      signals were recorded in two conditions: eyes open and eyes closed. Three trials
      were performed in each condition with a rest period of approximately 1 min. The
      intraclass correlation coefficients (ICCs) and standard error of measurement
      (SEM) were calculated. [Results] The investigation of ICC and SEM between trials
      showed that the Lyapunov exponent (ICC: 0.76-0.96, SEM: 0.03) and total mean
      velocity (ICC: 0.71-0.95, SEM: 0.05) were more reliable and repeatable than range
      and area (95% confidence ellipse), while area had the least reliability (ICC:
      0.49-0.77, SEM: 0.56). [Conclusion] The Lyapunov exponent can be considered an
      appropriate postural control index, and the evaluation of postural stability
      should be done by considering linear and nonlinear tools.

PMID- 29184287
TI  - Gross motor skill development of 5-year-old Kindergarten children in Myanmar.
AB  - [Purpose] The purpose of this study was to examine the gross motor skill
      development of 5-year-old Kindergarten children in Myanmar. [Subjects and
      Methods] Total 472 healthy Kindergarten children (237 males, 235 females) of 2016
      2017 academic year from four schools in urban area and four schools in rural area
      of Myanmar were recruited. The gross motor skill development of all subjects was
      assessed with the test of gross motor development second edition (TGMD-2). All
      subjects performed two trials for each gross motor skill and the performance was
      video recorded and scored. The assessment procedures were done according to the
      standardized guidelines of TGMD-2. [Results] The majority of subjects had average
      level of gross motor skill rank. The significant differences were found on the
      run and gallop of locomotor skills and the most of object control skills except
      the catch between males and females. The significant differences were also found
      between subjects from urban and rural areas. [Conclusion] Gross motor skill
      development of 5-year-old Kindergarten children in Myanmar had gender-based and
      region-based differences on both locomotor and object control skills. This study
      added a valuable information to the establishment of a normative reference of
      Kindergarten aged children for future studies.

PMID- 29184288
TI  - A new model of skeletal muscle atrophy induced by immobilization using a hook-and
      loop fastener in mice.
AB  - [Purpose] To study muscle atrophy, the muscle atrophy model mice have been used
      frequently. In particular, cast immobilization is the most common method to
      induce muscle atrophy. However, it is time consuming and often causes adverse
      events including skin injury, edema, and necrosis. The present study, we
      developed a hook-and-loop fastener (Velcro) immobilization method as a new,
      simple, and less invasive approach to induce muscle atrophy. [Subjects and
      Methods] Mice were bandaged in the knee joint extension and ankle plantar
      extension position. Muscle atrophy was induced by either winding a cast or Velcro
      around the limb. [Results] According to weight and fiber size, Velcro
      immobilization induced equivalent muscle atrophy to cast immobilization. Velcro
      immobilization reduced significantly the time for the procedure and the frequency
      of adverse events. [Conclusion] Velcro immobilization can induce muscle atrophy
      comparable to cast immobilization, but in a shorter time and with less
      complications. Velcro immobilization may contribute to the study of disuse muscle
      atrophy in clinical practice of physical therapy using a mouse model.

PMID- 29184289
TI  - Proprioceptive change impairs balance control in older patients with low back
      pain.
AB  - [Purpose] This study aims to determine the specific proprioceptive control
      strategy used during postural balance in older patients with low back pain (LBP)
      and non-LBP (NLBP) and to assess whether this strategy is related to
      proprioceptive decline and LBP. [Subjects and Methods] Pressure displacement
      center was determined in 47 older persons with LBP and 64 older persons with NLBP
      during upright stance on a balance board without vision. Gastrocnemius (GS) and
      lumbar multifidus muscle (LM) vibratory stimulations of 60 and 240-Hz,
      respectively, were applied to evaluate the relative contributions of different
      proprioceptive signals (relative proprioceptive weighting ratio, RPW) used in
      postural control. Age, height, weight, back muscle strength, L1/2 and L4/5 lumbar
      multifidus cross section area ratio, skeletal muscle mass index, sagittal
      vertical axis, and Roland-Morris disability questionnaire (RDQ) were evaluated.
      [Results] Compared with older patients with NLBP, those with LBP showed a lower
      RPW 240-Hz, lower L4/5 lumbar multifidus cross-sectional area ratio, and a
      significantly higher age and RDQ. Logistic regression analysis showed that RPW
      240-Hz and age were independently associated with LBP, after controlling for
      confounding factors. [Conclusion] Older patients with LBP decreased their
      reliance on GS (RPW 240-Hz) proprioceptive signals during balance control.

PMID- 29184290
TI  - Kinematic analysis of head, trunk, and pelvic motion during mirror therapy for
      stroke patients.
AB  - [Purpose] The purpose of this study was to investigate mirror therapy (MT)
      condition by analyzing kinematic parameters according to mirror size and angle.
      [Subjects and Methods] Three hemiparesis stroke patients and five healthy adults
      participated in this cross-sectional study. Kinematic parameters during the MT
      were collected over a total of 5 trials for each subject (3 mirror angles * 3
      mirror sizes). Center of pressure (COP) excursion data was collected by force
      plate, and other kinematic parameters by infra-red cameras. [Results] The larger
      the size and smaller the angle, the overall dependent variables decreased in all
      participants. Particularly, when virtual reality reflection equipment (VRRE) was
      used, the value of the flexion and the lateral tilt was the closest to the
      midline compared to all other independent variables. Moreover, it showed tendency
      of moving towards the affected side. Based on the results, MT for stroke patients
      has a disadvantage of shifting weight and leaning towards the unaffected side
      during therapy. [Conclusion] Therefore, it seems to be more effective in terms of
      clinics to apply VRRE to make up for the weak parts and provide more elaborate
      visual feedback.

PMID- 29184291
TI  - The effects of task-oriented training on hand dexterity and strength in children
      with spastic hemiplegic cerebral palsy: a preliminary study.
AB  - [Purpose] The purpose of this study was to investigate the effects of task
      oriented training (TOT) on hand dexterity and strength in children with spastic
      hemiplegic cerebral palsy. [Subjects and Methods] Twelve children with spastic
      hemiplegic cerebral palsy were randomly assigned to either the TOT group (n=6) or
      the control group (n=6). In both groups, conventional occupational therapy was
      performed 40-min/day, 2 times a week, for 4 weeks. In the TOT group, TOT was
      additionally performed for 20 min, and the control group received usual care. The
      box and block test (BBT) was performed to assess hand dexterity. Hand strength
      was also assessed using hand dynamometer. [Results] After intervention, the TOT
      group showed a significant improvement of hand dexterity. In the control group,
      BBT and grip strength were not significantly improved after intervention.
      [Conclusion] In clinical settings, we suggest that TOT may be used as an
      intervention to improve hand dexterity in children with spastic hemiplegic
      cerebral palsy.

PMID- 29184292
TI  - Cardiopulmonary rehabilitation program impact on prognostic markers in selected
      patients with resting and exercise-induced ventilatory inefficiency: a clinical
      trial.
AB  - [Purpose] Ventilatory limitation is a common problem in patients with chronic
      heart failure and pulmonary hypertension. Excess ventilation may arise from
      augmented ventilatory drive, over activity of chemoreceptors and muscle
      ergoreceptors, or premature onset of lactic acidosis. Exertional dyspnea can
      cause limitations in the activities of daily living and as a result, reduced
      quality of life for these patients. The aim of the present study was to evaluate
      the effect of cardiopulmonary rehabilitation program on ventilatory efficiency
      for these patients. [Subjects and Methods] Twenty five patients with chronic
      heart failure and twenty five patients with pulmonary hypertension and only forty
      of them completed the study. The training program consisted of interval aerobic
      training program, based on the results of cardiopulmonary exercise testing.
      Training period was about five months. Outcomes were ventilatory equivalent for
      CO2, (VE/VCO2 at anaerobic threshold), VO2 at anaerobic threshold, VO2 max and
      peak work load. Echocardiography parameters were also measured; right ventricular
      systolic pressure for patients with pulmonary hypertension and ejection fraction
      for patients with chronic heart failure. [Results] Both groups showed an
      improvement in ventilation during exercise in favor of patients with pulmonary
      hypertension. VE/VCO2 decreased by 6.65 in pulmonary hypertension and by 2.9 in
      chronic heart failure. Right ventricular systolic pressure decreased by 12.05
      mmHg in pulmonary hypertension and ejection fraction increased by 17.74% in
      chronic heart failure. [Conclusion] Physical therapy cardiopulmonary
      rehabilitation should be considered in managing patients with ventilatory
      limitation such as pulmonary hypertension and chronic heart failure.

PMID- 29184293
TI  - The effects of three types of piriform muscle stretching on muscle thickness and
      the medial rotation angle of the coxal articulation.
AB  - [Purpose] The purpose of this study was three kinds of stretching methods and
      measured the change in the thickness of the piriform muscle in real time using
      ultrasound images and compared the medial rotation angle of the coxal
      articulation. [Subjects and Methods] Fourty-five subjects who attend B University
      in Cheonan, divided into three groups. The subjects in these three groups then
      underwent stretching with flexion of coxal articulation over 90 degrees ,
      stretching with flexion of coxal articulation under 90 degrees , and muscle
      energy technique (MET) application. The main outcome measures were piriform
      muscle thickness and medial rotation angle of the coxal articulation. [Results]
      All groups showed decreased piriform muscle thickness and increased medial
      rotation angle of the coxal articulation. [Conclusion] Based on the above
      results, three kinds of piriform muscle stretching methods are effective of
      reduce muscle thickness and increase medial rotation angle of the coxal
      articulation.

PMID- 29184294
TI  - Effects of bedside self-exercise on oropharyngeal swallowing function in stroke
      patients with dysphagia: a pilot study.
AB  - [Purpose] The purpose of this study was to investigate the effect of self
      exercise on oropharyngeal swallowing function in patients with dysphagia.
      [Subjects and Methods] Nine patients with dysphagia after stroke were recruited.
      Self-exercise including effortful swallowing, tongue strengthening, and shaker
      exercise was performed 5 times a week for 4 weeks. Swallowing function was
      evaluated using the videofluoroscopic dysphagia scale (VDS) based on a
      videofluoroscopic swallowing study. [Results] There were significant differences
      in both the oral and pharyngeal phases of the VDS before and after the
      intervention. [Conclusion] This study demonstrated that bedside self-exercise is
      a positive method to improve oropharyngeal swallowing function in patients with
      dysphagia after stroke.

PMID- 29184295
TI  - Effects of jaw opening exercise on aspiration in stroke patients with dysphagia:
      a pilot study.
AB  - [Purpose] The purpose of this study was to investigate the effect of jaw opening
      exercise (JOE) on aspiration in patients with dysphagia after stroke. [Subjects
      and Methods] Three subjects were recruited. Isometric and isotonic JOE were
      performed using a rubber ball, 5 days a week for 4 weeks. Aspiration was
      evaluated using the penetration-a spiration scale (PAS) based on a
      videofluoroscopic swallowing study. [Results] All subjects showed a score
      reduction of at least 1 point and a maximum reduction of 2 points in the PAS in
      the liquid type. [Conclusion] This study confirmed that JOE can be used to reduce
      aspiration in patients with dysphagia after stroke.

PMID- 29184296
TI  - Effects of mental practice combined with electromyogram-triggered electrical
      stimulation for upper extremity function in stroke patients.
AB  - [Purpose] To investigate the effect of mental practice combined with
      electromyogram-triggered electrical stimulation (MP-EMG ES) on the upper
      extremity of stroke patients. [Subjects and Methods] Participants were randomly
      assigned to experimental group or control group. The experimental group received
      MP-EMG ES plus conventional rehabilitation therapy for 5 days per week for 4
      weeks. The control group received only conventional rehabilitation therapy.
      Outcome measure included the Fugl-Meyer Assessment (FMA) and Motor Activity Log
      (MAL). [Results] Experimental group showed more improved in the FMA, MAL-AOU, MAL
      QOM compared with the control group. [Conclusion] These results suggest that MP
      EMG ES improves the upper extremity of subacute stroke patients better than
      conventional rehabilitation therapy alone.

PMID- 29184297
TI  - The relationship between non-affected forelimb exercise and recovery after focal
      cerebral ischemia in acute phase.
AB  - [Purpose] In the present study, we hypothesized that exercise of the nonaffected
      forelimb in the early poststroke phase would stimulate the intact hemisphere,
      thereby influencing the hemisphere of the infarcted side and improving the
      performance of the hemiplegic limb. [Subjects and Methods] Adult male Sprague
      Dawley rats (8-10 weeks of age, weighing 250-300 g, n=12) were used and randomly
      divided into 3 groups: nonaffected forelimb exercise for 3 days and treadmill
      exercise 7 days after ischemia (ETF, n=6), resting for 3 days and treadmill
      exercise 7 days after ischemia (ETN, n=6), and after ischemia 10 days resting
      group. To validate nerve growth factor (NGF), western blot analysis was
      performed. The results were analyzed using SPSS for Windows version 18.0. and
      expressed as mean +/- standard deviation (SD). [Results] Early treadmill exercise
      increased the expression of NGF protein level in both ETE and ETN groups.
      Comparing between the nonaffected forelimb exercise and infarct hemisphere in NGF
      protein expression, the ETE group showed higher increase of NGF protein level in
      right hemisphere than ETN group, but there was no statistical significance.
      [Conclusion] The early treadmill exercise increased NGF protein expression levels
      in both hemispheres and the nonaffected forelimb exercise in the early poststroke
      recovery phase could enhance neuronal recovery after focal ischemia in rat
      models.

PMID- 29184298
TI  - Changes in rounded shoulder posture and forward head posture according to
      exercise methods.
AB  - [Purpose] This study aimed to determine the effect of forward head posture
      improving exercises on rounded shoulder posture when employing the self-stretch
      exercise, the McKenzie exercise, and the Kendall exercise as intervention methods
      based on previous studies that reported negative effects of unbalanced posture
      and musculoskeletal problems on forward head posture and rounded shoulder
      posture. [Subjects and Methods] The selected 28 subjects were randomly assigned
      into the McKenzie exercise group (n=9), the self-stretch exercise group (n=10),
      and the Kendall exercise group (n=9). To compare the forward head posture, the
      craniovertebral angle was used. To measure the rounded shoulder posture, the
      scapular index was used. [Results] There were significant differences in the
      craniovertebral angle and scapular index within the groups and no significant
      differences between the groups. [Conclusion] The result of this study showed that
      all interventions increased the craniovertebral angle and the scapular index,
      which revealed that the applied exercises had a positive effect on forward head
      posture and rounded shoulder posture.

PMID- 29184299
TI  - Differences in maximal strength and endurance of the tongue according to region
      in healthy adults.
AB  - [Purpose] The purpose of this study was to identify differences in maximal
      strength and endurance of the tongue among healthy adults. [Subjects and Methods]
      A total of 60 healthy volunteers (30 men; 30 women; age range, 20-26 years) were
      recruited and evaluated for maximal strength and endurance of the anterior and
      posterior regions of the tongue using the Iowa Oral Performance Instrument.
      [Results] Tongue strength in the anterior region was greater than that in the
      posterior region. In contrast, tongue endurance in the posterior region was
      greater than that in the anterior region. [Conclusion] In conclusion, these
      results confirm that the anterior region of the tongue exhibits greater strength,
      whereas the posterior region exhibits greater endurance.

PMID- 29184300
TI  - Influence of pilates training on the quality of life of chronic stroke patients.
AB  - [Purpose] This study was to observe the influence of Pilates training on the
      quality of life in chronic stoke patients. [Subjects and Methods] Forty chronic
      stroke patients participated in this study. They were divided into same number of
      experimental group (EG) and control group (CG). EG participated in a 60-min
      Pilates training program, twice a week for 12 weeks, while the CG did not
      participate in any exercise-related activities for the duration and participating
      in general occupational therapy without any exercise-related activities. Then the
      MMSE-K was performed before and after Pilates training to observe the influence
      of Pilates training on the quality of life in chronic stroke patients. [Results]
      Statistically significant improvement in the physical, social, and psychological
      domains was found in EG after the training. No statistically significant
      difference was found in all three quality of life domains for the CG. EG
      experienced a statistically significant improvement in all quality of life
      domains compared with that of CG. [Conclusion] Therefore, participation in
      Pilates training was found to effectively improve the quality of life in stroke
      patients. Pilates training involves low and intermediate intensity resistance and
      repetition that match the patient's physical ability and can be a remedial
      exercise program that can improve physical ability and influence quality of life.

PMID- 29184301
TI  - Effects of cervical stretching and cranio-cervical flexion exercises on cervical
      muscle characteristics and posture of patients with cervicogenic headache.
AB  - [Purpose] The present study aimed to conduct a comparative analysis of changes in
      mechanical characteristics of cervical muscles and cervical posture in patients
      with cervicogenic headache following exercise program intervention in order to
      present effective treatment methods for such patients. [Subjects and Methods] A
      total of 30 patients with cervicogenic headache were recruited and 15 patients
      were allocated to cervical stretching exercise group and 15 to cervical
      stretching exercise and cranio-cervical flexion exercise group. After 3 weeks of
      exercise intervention, craniovertebral angle and tone (Hz) and stiffness (N/m) of
      the suboccipital and upper trapezius muscles were measured. [Results] After the
      exercise program intervention, a greater amount of change in tone of suboccipital
      and upper trapezius muscles was found in the experimental group, as compared to
      the control group, but the difference was not statistically significant. Greater
      amount of change in muscle stiffness and craniovertebral angle was found in the
      experimental group, as compared to the control group. [Conclusion] Findings of
      the present study showed that cranio-cervical exercise was an effective form of
      exercise for changing muscle characteristics and posture in patients with
      cervicogenic headache. Such findings will be helpful in providing effective
      treatments for patients with cervicogenic headache.

PMID- 29184302
TI  - An analysis on muscle tone and stiffness of posterior cervical region during
      sling and plinth on static prone position.
AB  - [Purpose] The purpose of this study was to quantitatively analyze changes in
      muscle tone and stiffness in the posterior cervical region of individuals in a
      static prone position in a sling or on a plinth. [Subjects and Methods] Twenty
      four men in their 20s were divided into a sling group and a plinth group, and
      their changes in muscle tone and stiffness over time in the upper cervical
      region, lower cervical region, and upper trapezius muscles during a static prone
      position were measured. [Results] The sling group showed increases in the mean
      values of muscle tone and stiffness in the upper cervical region immediately
      after the suspension. In addition, this group exhibited statistically significant
      declines in the muscle tone and stiffness of the upper cervical region and a
      statistically significant decline in the muscle tone of the upper trapezius
      region. [Conclusion] The findings of this study suggest that for the treatment of
      the posterior upper cervical region after sling suspension in a static prone
      position, the time required to reduce the muscle tone and stiffness of this
      region should be taken into account.

PMID- 29184303
TI  - The influence of the vibration form roller exercise on the pains in the muscles
      around the hip joint and the joint performance.
AB  - [Purpose] The purpose of this study is to examine the influence of the vibration
      form-roller exercise on the pain in the hip joint and the joint performances.
      [Subjects and Methods] 30 adult patients were randomly sampled and divided into
      form-roller group (15) and the vibration form-roller group (15). The two groups
      were exposed to an exercise regimen of 3 sessions per week, over 4 weeks. Each
      session was composed of warming-up (5M), main exercises (20M), and five minutes
      of cool-down (5M). [Results] The result of this study, in the intra-group
      comparison of the Performance, the PRE group increase in the flexion, extension,
      and abduction of the hip joint, the VPRE group increase in flexion, extension,
      external rotation and internal rotation. In the comparison between groups, the
      VPRE group increase in the flexion and internal rotation. Through the intra-group
      comparison the pressure pain, the PRE group and the VPRE group decreases in the
      all muscles. In the comparison between the groups, there was increase in the
      iliotibial tract of the VPRE group. [Conclusion] The result of this study the
      effect of the form-roller & vibration form-roller exercises. Therefore, various
      exercise methods would have to be developed in order to overcome the limitations
      in the existing form-roller exercises.

PMID- 29184304
TI  - Easy assessment tool for motor imagery ability in elementary scool students.
AB  - [Purpose] The final purpose of the present study was to propose easy and quick
      mental rotation task. Since subjects can easily understand mental rotation task
      that they have to do, the task is considered to be available in particular
      children. However, existing mental rotation task using specific software asked
      subjects more than ten trials per one pictured stimulus, meaning that relatively
      long time is required to accurately measure. Thus, children have difficulty to
      keep their attention during the existing task and to demonstrate their ability
      accurately. To address the purpose of the present study, the performance of
      mental rotation task using paper was investigated whether the performance has
      similar characteristics to an existing mental rotation task using specific
      software, in order to verify the usability of the task using paper. [Subjects and
      Methods] Sixty-three elementary school participants were asked to determine
      whether a rotating hand picture was left or right as quickly as possible and
      indicate it by writing a diagonal line on the paper. The total time required
      judgment of 16 pictures and the number of judgment errors were counted. [Results]
      The number of judgment errors increased with an increasing stimulus rotation
      angle. Also, the mental rotation time improved with age. [Conclusion] These
      results suggest that the performance of mental rotation using paper has the same
      characteristics as the existing method using specific software. Therefore, the
      mental rotation using paper would be practical method for subjects having
      difficulty to keep attention relatively long time, such as elementary school
      children.

PMID- 29184305
TI  - The effect of knee flexion angles and ground conditions on the muscle activation
      of the lower extremity in the squat position.
AB  - [Purpose] The purpose of this study is to research the most effective knee
      flexion angle and ground condition in the squat position. [Subjects and Methods]
      The subjects of this study were 15 female college students who were able to
      perform squat movements and who had never previously experienced surgery,
      orthopedic disease, or musculoskeletal impairment. This study was conducted to
      examine changes of muscle activation of low-extremity muscles at different knee
      flexion angles of 70 degrees , 90 degrees , and 100 degrees . Balance Pad (Aero
      Step, TOGU, Germany) was used as unstable ground. Surface electromyogram (4D-MT &
      EMD-11, Relive, Korea) was used for measuring muscle activation. Measured muscles
      were vastus medialis, biceps femoris, tibialis anterior, and gastrocnemius.
      Muscle activation was determined by the root mean square (RMS). [Results] There
      was a difference in muscle activation of the vastus medialis and tibialis
      anterior according to the change of the knee flexion angle with the stable
      ground. However, there was no difference in muscle activation of the lower
      extremity muscles according to the change of the knee flexion angle with the
      unstable ground. [Conclusion] These results suggest that changes in the angle of
      the knee flexion with the stable ground affect the muscle activation of the
      vastus medialis and tibialis anterior. It was found that as the joint angle
      increases, muscle activation also increases. However, ground condition does not
      affect muscle activation.

PMID- 29184306
TI  - No significant correlation between the intensity of static stretching and
      subject's perception of pain.
AB  - [Purpose] The purpose of this study was to determine whether the intensity of
      static stretching measured quantitatively is related to subjects' perception of
      pain. [Subjects and Methods] Sixty-eight participants were recruited. Static
      stretching was performed once for 30 seconds while maintaining the knee at 0
      degrees  flexion and was continued to the point where pain was recognized. The
      intensity of stretching exerted by the practitioner was quantitatively measured
      by using a handheld dynamometer (HHD). A subject's pain scaled on one's
      perception was measured by using the visual analog scale (VAS). [Results] No
      significant correlation was found between the intensity of stretching and the VAS
      score representing the subject's pain scaled on one's perception. In this study,
      the most frequent VAS score was 7, and the mean VAS score was 5.57 +/- 1.77. The
      stretching intensity measured by using a HHD ranged from 28.4 to 133.0 N (mean,
      72.04 +/- 22.37 N). [Conclusion] This study showed that the intensity of
      stretching quantitatively measured by using HHD did not correlate with the degree
      of pain reported by the subjects. Therefore, subjective responses cannot
      guarantee a consistent application of intensity.

PMID- 29184307
TI  - Does transcutaneous electrical nerve stimulation (TENS) simultaneously combined
      with local heat and cold applications enhance pain relief compared with TENS
      alone in patients with knee osteoarthritis?
AB  - [Purpose] The purpose of this study was to investigate whether transcutaneous
      electrical nerve stimulation simultaneously combined with local heat and cold
      applications enhances pain relief compared with transcutaneous electrical nerve
      stimulation alone in patients with knee osteoarthritis. [Subjects and Methods]
      Fourty-five patients with knee osteoarthritis participated in this study. They
      were randomly assigned to the following three interventions: transcutaneous
      electrical nerve stimulation simultaneously combined with local heat using a hot
      pack; combined with local cold using a cold pack; and transcutaneous electrical
      nerve stimulation alone. In each intervention, the knee pain level during walking
      and standing up from a chair, as well as dynamic balance and gait ability were
      evaluated immediately before and after a single intervention using the visual
      analogue scale and the timed up & go test, respectively. [Results] A significant
      improvement in dynamic balance and gait ability was only observed immediately
      after transcutaneous electrical nerve stimulation simultaneously combined with
      local heat application, although the degree of pain relief during standing and
      walking were comparable among the three interventions. [Conclusion] These results
      suggest that transcutaneous electrical nerve stimulation simultaneously combined
      with local heat application can immediately improve not only knee pain during
      standing and walking but also dynamic balance and gait ability in patients with
      knee osteoarthritis.

PMID- 29184308
TI  - Intrarater reliability of measuring the patella position by ultrasonography in
      weight-bearing condition.
AB  - [Purpose] The aim of this study was to determine the intrarater reliability of
      using ultrasonography as a measurement tool to assess the patella position in a
      weight-bearing condition. [Subjects and Methods] Ten healthy adults participated
      in this study. Ultrasonography was used to assess the patella position during
      step down with the loading knee in flexion (0 degrees  and 20 degrees ). The
      distance between the patella and lateral condyle was measured to represent the
      patella position on the condylar groove. Two measurements were obtained on the
      first day and the day after 1 week by the same investigator. [Results] Excellent
      intrarater reliability, ranging from 0.83 to 0.93, was shown in both conditions.
      Standard errors of the measurements were 0.5 mm in the straight knee and 0.7 mm
      in the knee flexion at 20 degrees . Minimal differences in knee flexion at 0
      degrees  and knee flexion at 20 degrees  were 1.5 mm and 1.9 mm, respectively.
      [Conclusion] Ultrasonography is a reliable assessment tool for evaluating the
      positional changes of the patella in weight-bearing activities, and it can be
      easily used by practitioners in the clinical setting.

PMID- 29184309
TI  - Reliability and validity of angle measurements using radiograph and smartphone
      applications: experimental research on protractor.
AB  - [Purpose] The present study aimed to demonstrate the following by using
      measurements for the definite angles provided by the digital protractor: inter
      rater reliability and validity in radiograph measurements and smartphone
      application measurements. [Subjects and Methods] The subject angles were 26
      angles between 15 degrees  and 180 degrees  that were selected randomly using a
      computer. Three examiners measured the angles using the radiograph and smartphone
      application. The radiograph was obtained at a position 250 cm from the chest
      shooting cassette holder. The smartphone photograph was obtained at positions 50,
      100, 150, 200, and 250 cm from the holder. [Results] Under all conditions, intra
      class correlation coefficients showed 0.999. The correlation coefficient was
      0.999 for all conditions. The mean absolute difference to the protractor was
      <=0.28 degrees  for all conditions. [Conclusion] In comparison with the
      protractor, radiograph measurements and smartphone application measurements, the
      results of the present study showed high inter-rater reliability, validity, and
      small error. The results indicated that radiograph and smartphone application
      measurements could be used as criteria of validity in angle measurements. It
      supported the legitimacy of high-quality previous studies that used radiograph
      measurements as a criterion for validity.

PMID- 29184310
TI  - Effects of single and dual tasks during walking on spatiotemporal gait parameters
      of community-dwelling older.
AB  - [Purpose] This study aimed to investigate the effects of single and dual motor
      tasks on walking in the elderly. [Subjects and Methods] Data of 308 community
      dwelling elderly people were analyzed. Spatiotemporal gait data were obtained
      using the OPTO Gait system. The gait ability test was conducted under single- and
      dual-task conditions. [Results] Age and task main effects showed significant
      difference. Interaction did not show any significant difference. [Conclusion] Our
      results showed that gait performance decreased during dual task compared to
      single task. Moreover, we found that the higher the age, the greater the effect
      on dual tasks. Further research is needed to determine how to improve dual task
      abilities in older adults.

PMID- 29184311
TI  - Dual task training effects on balance and hand functions of stroke patients.
AB  - [Purpose] The purpose of this research is to take a look at the influences of the
      dual task training on the hand function and the balance ability of the stroke
      patients. [Subjects and Methods] The dual task training was applied to 2 stroke
      hemiplegia patients. The dual task training had been carried out for 30 minutes
      by each session for 5 days a week for 3 weeks. The evaluations had been carried
      out 5 times for 3 weeks before and after the intervention. And the changes of the
      hand function had been measured by using the box and block test. And, for the
      changes of the balancing ability, the Berg Balance Scale was used. [Results] Both
      the hand function and the balancing ability of the subjects were improved after
      the dual task training. [Conclusion] Through the results of the research, it was
      able to confirm that the dual task training is effective for the enhancements of
      the hand function and the balancing ability of the stroke patients.

PMID- 29184312
TI  - Effects of 4 weeks of dynamic neuromuscular stabilization training on balance and
      gait performance in an adolescent with spastic hemiparetic cerebral palsy.
AB  - [Purpose] The purpose of this study investigated the effects of 4 weeks of
      dynamic neuromuscular stabilization training on balance ability. [Subject and
      Methods] An adolescent with spastic hemiparetic cerebral palsy was recruited. The
      subject performed 4 weeks of dynamic neuromuscular stabilization training. We
      assessed the balance subtest of the Bruininks-Oseretsky Test of Motor Proficiency
      Second Edition, the 10-meter walk test, and the 6-min walk test. [Results] The
      balance subtest scores were improved significantly after training. [Conclusion]
      This study suggests that 4 weeks of dynamic neuromuscular stabilization training
      is effective for improving balance and gait performance in spastic hemiparetic
      cerebral palsy.

PMID- 29184313
TI  - Retraction: Intra-rater and inter-rater reliability of the portable gait
      rhythmogram in post-stroke patients.
AB  - [This retracts the article on p. 874 in vol. 29.].

PMID- 29184314
TI  - Reforming Community Medicine in Line with the Country's Health Priorities - Let's
      Make it Relevant and Rational.

PMID- 29184316
TI  - Erratum.
AB  - [This corrects the article on p. 131 in vol. 42, PMID: 28852273.].

PMID- 29184315
TI  - Is There an Association between the Duration of Stay in the Medical Colleges and
      the Smoking Behavior among Medical Students? A Cross-sectional Study.
AB  - Background: Health-care providers must be at the forefront of tobacco cessation
      to ensure a downward shift in tobacco use. Medical schools constitute an
      important site for education and cessation efforts. Health-care professionals
      play a substantial role in influencing patients' lifestyle choices including
      tobacco cessation. Objectives: To examine the association between the duration of
      stay in the medical colleges and the smoking behavior among the medical students
      in Karnataka, India. Materials and Methods: One government and four private
      medical colleges were selected using stratified random sampling technique for
      this cross-sectional study. Sample size was 3288 medical students. A pretested
      self-administered questionnaire was used to collect data. SPSS version 12.0 was
      used for data analysis. The statistical methods used were frequencies,
      proportions, and Chi-square test. Results: Mean age of the study participants was
      20.68 +/- 2.05 years for males and 20.20 +/- 1.91 years for females. Number of
      smokers among medical students after joining medical college increased 2.7 times.
      The duration of stay in the medical colleges was positively associated with the
      smoking behavior (P < 0.0001) among medical students, and the increase in the
      number of smokers reached up to 259.6% during internship. Conclusion: Smoking
      among medical students increases along with their stay in medical college.

PMID- 29184317
TI  - Building Evidence for Coverage of Fully Vaccinated Children of 12-23 Months of
      Age across Districts of North India, 2015.
AB  - Context: Unprecedented low coverage (63%) of fully vaccinated (FV) children in
      the recent round of national survey district level household (HH) and facility
      survey 4 (DLHS-4) propelled health system of Himachal Pradesh for an independent
      rapid assessment of FV coverage. Aim: The aim of the study was to assess the FV
      coverage among 12-23-month old children in the state. Settings and Design: A
      community-based survey with an interviewer-administered questionnaire was carried
      out in all 12 districts of Himachal Pradesh from September 2015 to January 2016.
      Subject and Methods: WHO 30 * 7 cluster technique was used. Statistical Analysis
      Used: Chi-square and unpaired Student's t-test along with 95% confidence
      intervals. Results: A total of 2492 children across 35,551 HHs (2.4% of state
      share) were surveyed with FV coverage of 98.1% (95% confidence interval [CI]:
      97.5-98.6) and 86% (95% CI: 84.6-87.3) based on history and card, respectively.
      Conclusions: The reported FV coverage in the current study was observed too high
      in the state as reported in earlier round of the national surveys (except DLHS
      4).

PMID- 29184318
TI  - Linkages between Hypertension and Coronary Heart Disease in India: Evidence from
      India Human Development Survey-2 (2011-2012).
AB  - Background: Cardiovascular diseases (CVDs) are the leading causes of death
      globally (nearly 17.5 million deaths/year). Hypertension and coronary heart
      disease (CHD) are two of the most important CVDs. There is a dearth of studies at
      a large scale in India to ascertain the factors as well as social differentials
      in the prevalence of heart disease associated with hypertension. This paper
      attempts to bridge the gap in the relevant area. Methodology: Secondary analysis
      of the data obtained from India Human Development Survey (IHDS), conducted in two
      rounds in 2004-2005 and 2011-2012, was done (n = 147,201). Bivariate and logistic
      regression analyses have been used. Results: In India, the prevalence for CHD is
      1.1% for 2011-2012. Findings showed that persons with hypertension are 11 times
      (odds ratio [OR] = 11.58, P < 0.01) more likely to be affected by CHD among
      adults (15 and above years) as compared to nonhypertensive adults. When the odds
      are adjusted for socioeconomic and demographic variables, hypertensives are found
      to be 5 times more likely (OR = 5.096, P < 0.01) to be having CHD as compared to
      nonhypertensives. Conclusions: The unadjusted odds of suffering from CHD when
      hypertension is a predictor are much higher than when the odds are adjusted for
      socioeconomic and demographic variables. Along with hypertension, age, education,
      and place of residence have also been found to be important determinants of CHD.

PMID- 29184319
TI  - A Comparative Study of Depression and Associated Risk Factors among Elderly
      Inmates of Old Age Homes and Community of Rajkot: A Gujarati Version of the
      Geriatric Depression Scale-Short Form (GDS-G).
AB  - Background: The prevalence of depression among elderly people varies across
      different setups such as old age homes (OAHs), community, and medical clinics.
      Aims: The aim of this study was to compare the epidemiological factors pertaining
      to depression among elderly residents of OAHs and community, using a new Gujarati
      version of the Geriatric Depression Scale-Short Form (GDS-G). Settings and
      Design: A cross-sectional, epidemiological study conducted in an urban setup of
      Western India. Materials and Methods: All the eligible 88 elderly residents of
      all the six OAHs and 180 elderly residents from the same city were administered a
      pretested semistructured questionnaire having the GDS-G form. Statistical
      Analysis: Descriptive statistics, odds ratio, Spearman's rank correlation test.
      Results: The elderly of OAHs were more depressed compared to those of community
      (odds ratio = 1.84; 95% confidence interval = 1.09-3.06). Older age, females,
      weaker family ties, economic maladies, poorer self-perception of health status,
      presence of chronic ailments, absence of recreational activity, lack of prayers,
      impaired sleep, history of addiction emerged as the predictors of depression in
      both the setups. More health complaints and a later self-perception of visit to a
      doctor were found among the depressed than the nondepressed in both the setups.
      Conclusions: Depressive symptoms were quite high among the elderly in both the
      setups. Special attention should be given toward health checkups of depressed
      persons in the OAH and improvement of family ties among depressed persons of the
      community.

PMID- 29184320
TI  - Neck Circumference: Independent Predictor for Overweight and Obesity in Adult
      Population.
AB  - Background: Neck circumference (NC) measurement, an index of upper body fat (BF)
      distribution, seems promising as a community-based screening measure for
      overweight and obesity in want of evidence on its validity as a screener.
      Objective: The objective of this study was to determine the validity of NC as a
      screener for overweight and obesity in adults in community settings against BF
      percentage (BF%). Materials and Methods: This cross-sectional community-based
      study involved data collection on a predesigned, pretested, and semi-structured
      schedule that included the sociodemographic characteristics and anthropometric
      measurements of respondents. Results: NC correlated positively with body weight,
      waist circumference, and hip circumference. NC was found to have good
      discriminatory power with cutoff values of 36.55 cm for males and 34.05 cm for
      females, with maximum sensitivity and specificity to predict overweight and
      obesity in comparison to direct BF% estimation on receiver operating
      characteristic analysis. Conclusion: NC has a fair validity as a community-based
      screener for overweight and obese individuals in the study context. Further
      studies may be carried out to explore the generalizability of this observation.

PMID- 29184321
TI  - Rapid Response to Syphilis Outbreak among Female Sex Workers.
AB  - Background: Outbreak of syphilis, i.e., 16 cases of rapid plasma reagin (RPR)
      reactive cases of syphilis was reported in Community Based Organization (CBO)
      Sahyog of Surat, India, from April to August 2014. The aim of the study was to
      find risk factors and take immediate actions to prevent spread. Materials and
      Methods: Outbreak investigation of 16 Female Sex Workers of CBO Sahyog in Surat
      who were found Rapid Plasma Reagin (RPR) and Treponema Pallidum Hemagglutination
      Assay (TPHA) positive from April to August 2014; was carried out. Clinico
      epidemiological and laboratory-based evidence for different sexually transmitted
      infections (STIs) conducted at Government Medical College, New Civil Hospital,
      Surat. Root cause analysis (RCA) of index case was carried out. Results: Desk
      review for the past 3 years data of STI revealed total STI cases as 88 (2011), 95
      (2012), and 130 (2013), of which 4, 2, and 2 found RPR reactive, respectively.
      Data from April to August 2014 revealed 16 RPR reactive cases and confirmed by
      TPHA. On examination, one had ulcerative cervical lesion, rest did not have any
      symptoms of syphilis. Eleven had vaginal/cervical discharge, 11 had lower
      abdominal pain. A total of 11 had unprotected sex, 7 encountered condom tear in
      the past 6 months, and 5 reported sexual violence. Seven had sexual activity
      under influence of alcohol. Laboratory investigation revealed two as HIV
      positive. RPR reactivity reported highest (9 out of 16) from same area of
      hotspot. RCA of probable index case revealed factors responsible as violence and
      nonuse of condoms. Conclusions: Outbreak investigation revealed one probable
      index case. All 16 treated with injection Penidure. Violence or condom tear is
      responsible for the spread. Crisis management team should be strengthened.

PMID- 29184322
TI  - Situational Analysis of Sickle Cell Disease in Gujarat, India.
AB  - Background: Sickle cell disease (SCD) is a major public health concern in tribal
      community not only in Gujarat but also globally. Gujarat, a western state of
      India, has 89.12 lakh tribal populations and is expected to have at least
      9,00,000 sickle cell trait and 70,000 SCD patients. The aim of the present review
      is to document the prevalence of SCD in various communities and various screening
      methods adapted. Methodology: An in-depth literature review was carried out using
      available search engines such as Cochrane Library, PubMed, Scopus etc. and
      published articles, and government reports/policy documents with reference to SCD
      were gathered. Results: A total of 17 original research articles and 2
      policy/program documents are included in this review. The review suggests a
      prevalence of 0.6%-35% studies conducted among medical students, tribal
      schoolchildren, and tribal adolescents, with diverse screening methodologies.
      Conclusion: A diverse prevalence is observed in this review. Various screening
      methods such as dithionite turbidity test/hemoglobin/high-performance liquid
      chromatography methods were used to estimate the prevalence, citing the need for
      standardization. It was also found that not only tribal population, but also
      nontribal population have the risk of getting SCD that needs to be further
      investigated properly. Qualitative studies with SCD patients are required to
      understand the quality of life and morbidity pattern.

PMID- 29184323
TI  - Stress and Stressors among Medical Undergraduate Students: A Cross-sectional
      Study in a Private Medical College in Tamil Nadu.
AB  - Background: Medical education is perceived as being stressful, and a high level
      of stress may have a negative effect on cognitive functioning and learning of
      students in a medical school. Objectives: To (a) assess the perceived stress
      among medical undergraduate students, (b) identify the sources of stress, and (c)
      find an association of perceived stress with sociodemographic characteristics and
      various stressors. Materials and Methods: A cross-sectional study was conducted
      among medical undergraduate students in a private medical college in Tamil Nadu.
      A total of 750 medical students from 1st year to final year were invited to
      participate in the study. Self-administered questionnaire was used to collect
      data regarding sociodemographic profile, perceived stress using perceived stress
      scale-14 and academic, psychosocial and environmental stressors. Descriptive
      statistics was used to describe the sociodemographic characteristics, sources of
      stress and perceived stress. Logistic regression analyses were carried out to
      assess determinants of stress. Results: The overall response rate was 93.33% (700
      out of 750 students). The mean perceived stress score was 25.64 +/- 5.44. Higher
      age-group, year of studying bachelor of medicine and bachelor of surgery,
      vastness of academic curriculum, fear of poor performance in examination, lack of
      recreation, loneliness, family problem, and accommodation away from home were
      important determinants of perceived stress. Conclusions: The perceived stress was
      higher among higher age group and final year medical students. Academic,
      psychosocial, and environmental stressors are associated with perceived stress.
      Reframing the academic curriculum and examination patterns, incorporating
      recreational and sports activities, and establishment of counseling cells in the
      institution is needed.

PMID- 29184324
TI  - Status of Iodine Nutrition among Pregnant Women Attending Antenatal Clinic of a
      Secondary Care Hospital: A Cross-sectional Study from Northern India.
AB  - Background: Daily requirement of iodine increases during pregnancy making
      pregnant women a high-risk group for iodine deficiency disorders. The limited
      available literature shows that even in iodine sufficient population, pregnant
      women are iodine deficient. Objective: The objective of this study is to assess
      the current iodine nutrition status among pregnant women in Ballabgarh, district
      Faridabad, Haryana. Materials and Methods: Pregnant women were recruited from
      antenatal clinic (ANC) of subdistrict hospital (SDH), Ballabgarh, Haryana.
      Consecutive sampling strategy was followed to recruit pregnant women, and women
      of all trimesters were included in the study. Urinary iodine estimation was done
      using simple microplate method, and salt iodine was estimated using iodometric
      titration. The study was approved by Institute Ethics Committee, All India
      Institute of Medical Sciences (AIIMS), New Delhi. Results: Out of the total 1031
      pregnant women, 90.9% were using adequately iodized salt. Median (interquartile
      range [IQR]) salt consumption by the pregnant women was 8.3 (6.7, 11.1) g/day.
      Median (IQR) urinary iodine concentration (UIC) for the pregnant women was 260
      (199, 323) MUg/L. Only 13.5% of pregnant women had insufficient iodine intake
      (UIC <150 MUg/L). There was no significant difference in median UIC values by
      household salt iodine content and across three trimesters of pregnancy.
      Conclusion: Iodine nutrition status of the pregnant women attending ANC clinic of
      SDH Ballabgarh was adequate with attainment of universal salt iodization goal of
      >90% adequately iodized salt coverage in the study population.

PMID- 29184325
TI  - A Longitudinal Study to Assess the Role of Sanitary Inspections in Improving the
      Hygiene and Food Safety of Eating Establishments in a Tertiary Care Hospital of
      North India.
AB  - Introduction: Food safety inspections serve two purposes; determine compliance
      with the law and gather evidence for enforcement if there is noncompliance. The
      present study was conducted to assess the role of regular inspections on food
      safety in hospital premises. Methodology: This was an intervention based before
      and after study. A tool was prepared based on the Food Safety and Standards
      Regulations (FSSR) (in India) 2011. This included major, critical, and highly
      critical domains. Each item in the tool scored between 1 and 3 (poor,
      satisfactory, and good). Based on this, each eating establishment (EE) was given
      a score on conformance to FSSR 2011. Monthly inspection was made over a year and
      corrective actions were suggested. Results: The minimum preintervention score was
      (41.28%), and maximum was (77.25%). There was no significant association between
      type of meal services and score EE (P > 0.05). Higher proportion of EEs within
      the hospital building had a satisfactory and good score as compared to EEs
      outside the hospital building but within hospital premises (P < 0.05).
      Postintervention, there was a significant change (increase) in the scores of EEs.
      There was a significant increase in mean scores of EEs under major domains namely
      maintenance, layout of equipment, monitoring an detection, and elimination of
      food sources to the pests. Under critical and highly critical domains personal
      cleanliness, training, and self-inspection by food business operators improved
      significantly. Conclusion: Regular inspections can improve the food safety
      standards in EEs.

PMID- 29184326
TI  - Mapping Neonatal Mortality in India: A Closer Look.
AB  - Introduction: Fifty-three percent of Indian under-5 deaths occur during the
      neonatal age group. Recognizing that there is a lack of illustrated district
      level data on neonatal mortality in India, we mapped this to visually highlight
      districts where neonatal health issues require the most attention. Methods:
      District-level estimates of 596 Indian districts were used to generate maps and
      to illustrate neonatal mortality rates (NMRs), absolute numbers of neonatal
      deaths; the best and worst performing districts (positive and negative deviants)
      in each Indian state; the neonatal female/male death ratio; and district lag in
      NMR reductions. Results: The NMR ranged from 4.3 (Kannur, Kerala) to 65.1 (Datia,
      Madhya Pradesh), with the mean NMR being 29.8. Almost two-thirds of the districts
      (n = 380, 63.7%) had NMRs between 20 and 40. The top third of neonatal deaths
      could be accounted for by just 71 districts of a total of 596. Conclusion: There
      is an urgent need for up-to-date data on district-level neonatal mortality in
      India.

PMID- 29184328
TI  - Changing Trends in Sexually Transmitted Infections at a Rural-based Tertiary
      Health-care Center in Gujarat: An 8-Year Study.

PMID- 29184327
TI  - Indicators to Ensure Treatment Initiation of All Diagnosed Sputum Positive
      Pulmonary Tuberculosis Patients under Tuberculosis Control Programme in India.
AB  - Background: Pretreatment loss to follow-up (PTLFU) is used as performance
      indicator of Revised National Tuberculosis Control Programme (RNTCP) of India.
      Objective: To document the PTLFU, identify additional indicators and examine
      documentation of all the diagnosed sputum positive pulmonary tuberculosis (PTB)
      patients under RNTCP. Methodology: Tuberculosis (TB) laboratory, referral for
      treatment registers, and referral forms were perused for information on sputum
      positive PTB patients diagnosed from January to June 2014, in 3 TB Units in
      Chennai. Results: PTLFU was 24% (572 out of 2361). However, in pursuance with the
      principle of ensuring that all diagnosed patients must be started on treatment
      following referral, it was inflated to 44% (1046 out of 2361). Conclusion: The
      existing PTLFU indicator does not reflect the proportion of treatment initiation
      of all diagnosed smear-positive PTB patients. We propose additional indicators
      for monitoring referral and treatment initiation of all diagnosed sputum positive
      PTB patients.

PMID- 29184329
TI  - Neonatal Transport: The Long Drive has Not Even Begun.

PMID- 29184330
TI  - An Integrated Disease Surveillance Project Concern for Kala-azar: Does the
      Framework in Nonendemic Regions Need an Overhaul?

PMID- 29184332
TI  - As I Sign Off.

PMID- 29184331
TI  - "Scratches/Abrasions without Bleeding" Cause Rabies: A 7 Years Rabies Death
      Review from Medical College Shimla, Himachal Pradesh, India.

PMID- 29184333
TI  - Status of Cognitive Testing of Adults in India.
AB  - The assessment of cognitive function is a challenging yet an integral component
      of psychological, psychiatric, and neurological evaluation. Cognitive assessment
      tools either can be administered quickly for screening for neurocognitive
      disorders or can be comprehensive and detailed to identify cognitive deficits for
      the purpose of localization, diagnosis, and rehabilitation. This article is a
      comprehensive review of published research that discusses the current challenges
      for cognitive testing in India, available tools used for the assessment of
      cognitive function in India, and future directions for cognitive testing in
      India.

PMID- 29184334
TI  - Efficacy and Safety of Tacrolimus in Myasthenia Gravis: A Systematic Review and
      Meta-analysis.
AB  - Aims: This study was designed to determine whether treatments with tacrolimus
      would provide benefit for patients with myasthenia gravis (MG). Materials and
      Methods: The databases of Medline, EMBASE, the Cochrane Library, and four Chinese
      databases were searched for eligible studies. Weighted mean differences and
      standardized mean differences (SMD) with corresponding 95% confidence intervals
      (CIs) were used to summarize the primary outcome, namely, steroid-sparing effect
      of tacrolimus in maintaining minimal manifestations, and the secondary outcome,
      namely, the effect of tacrolimus in reducing the severity of MG, respectively.
      Results: After systematic retrieval, 13 researches with two randomized controlled
      trials (RCTs) and 11 prospective open-label single-arm clinical trials were
      included in the study. For the primary outcome of two RCTs, one RCT which was
      followed up for 1 year showed a positive effect and the other RCT which was
      associated with treatment duration of 28 weeks showed a negative result. For the
      secondary outcome, meta-analyses of other 11 trials showed a benefit effect,
      overall. For the quantitative MG (QMG) score, there were significant differences
      with high heterogeneity (SMD: 2.93; 95% CI: 1.14-4.73; I2 = 86%). In contrast,
      for MG activities of daily living (MGADL) score, it was reduced by tacrolimus
      with significant SMD and less heterogeneity (SMD: 0.59; 95% CI: 0.33-0.85; I2 =
      7%). Adverse effects were mentioned as mild. Discussion: The opposite results of
      two RCTs showed that tacrolimus with enough treatment duration might have
      positive steroid-sparing effect. The most possible cause of heterogeneity in the
      outcome of QMG score between trials was the baseline severity of MG. Conclusion:
      The above finding suggests that there might be a potential beneficial role with
      no serious side effects of tacrolimus, and additional better RCTs including
      larger sample sizes and long-term study are needed to confirm or refute the
      results.

PMID- 29184335
TI  - Johann Bernhard Aloys von Gudden and the Mad King of Bavaria.
AB  - Bernhard von Gudden was a psychiatrist in Prussia and he was summoned in March
      1886 to examine King Ludwig II for his apparently insane activities like,
      profligate spending and erratic behaviour. A team of four estimable psychiatrists
      pronounced that he was not capable ruling. Consequently, he was dethroned and
      kept in a castle under supervision of von Gudden. Gudden championed the idea of
      'no restraint' and advocated free movement of insane persons and one evening in
      June, he accompanied the King during an evening stroll to a lake. A few hours
      later, the corpus of both of them were recovered under mysterious circumstances.
      Autopsy suggested that the King was drowned but no post-mortem examination was
      performed on von Gudden. There are plenty of controversies regarding their death
      like, murder, accidental death or even natural death from cardiac arrest
      following immersion in cold water, but no incontrovertible conclusion could be
      arrived at, even after scrupulous analysis by historians and even the diagnosis
      of insanity of the King has been doubted. Some even suggested that the opinion of
      psychiatrists were sought as a pretense in order to depose the King.

PMID- 29184336
TI  - Speech Signal Analysis and Pattern Recognition in Diagnosis of Dysarthria.
AB  - Background: Dysarthria refers to a group of disorders resulting from disturbances
      in muscular control over the speech mechanism due to damage of central or
      peripheral nervous system. There is wide subjective variability in assessment of
      dysarthria between different clinicians. In our study, we tried to identify a
      pattern among types of dysarthria by acoustic analysis and to prevent
      intersubject variability. Objectives: (1) Pattern recognition among types of
      dysarthria with software tool and to compare with normal subjects. (2) To assess
      the severity of dysarthria with software tool. Materials and Methods: Speech of
      seventy subjects were recorded, both normal subjects and the dysarthric patients
      who attended the outpatient department/admitted in AIMS. Speech waveforms were
      analyzed using Praat and MATHLAB toolkit. The pitch contour, formant variation,
      and speech duration of the extracted graphs were analyzed. Results: Study
      population included 25 normal subjects and 45 dysarthric patients. Dysarthric
      subjects included 24 patients with extrapyramidal dysarthria, 14 cases of spastic
      dysarthria, and 7 cases of ataxic dysarthria. Analysis of pitch of the study
      population showed a specific pattern in each type. F0 jitter was found in spastic
      dysarthria, pitch break with ataxic dysarthria, and pitch monotonicity with
      extrapyramidal dysarthria. By pattern recognition, we identified 19 cases in
      which one or more recognized patterns coexisted. There was a significant
      correlation between the severity of dysarthria and formant range. Conclusions:
      Specific patterns were identified for types of dysarthria so that this software
      tool will help clinicians to identify the types of dysarthria in a better way and
      could prevent intersubject variability. We also assessed the severity of
      dysarthria by formant range. Mixed dysarthria can be more common than clinically
      expected.

PMID- 29184338
TI  - Rapid Clinical Score for the Diagnosis of Tuberculous Meningitis: A Retrospective
      Cohort Study.
AB  - Objective: The aim of our study was to retrospectively validate a previously
      described rapid clinical score (RCS) in distinguishing tuberculous meningitis
      (TBM) from viral meningitis (VM) in people who are at increased risk of
      tuberculosis, as well as from cryptococcal meningitis (CM) in HIV-infected
      patients. Methods: We performed a retrospective study of patients admitted with a
      diagnosis of aseptic meningitis between January 2012 and December 2015, to a
      referral hospital for infectious diseases. The variables included in RCS were
      duration of symptoms before admission, neurological stage, cerebrospinal fluid
      (CSF) to blood glucose ratio, and CSF protein. We included in this retrospective
      study 31 patients with definite or probable TBM including 14 HIV-infected
      patients, 62 HIV-noninfected patients with VM, and 18 HIV-infected patients with
      CM. Results: The sensitivity of RCS to distinguish TBM from VM was 96.7%, with a
      specificity of 81.1% and the area under the receiver operating characteristic
      (ROC) curve was 0.949 (0.90-0.99). When all four criteria from the RCS were
      present, the specificity increased at 100%. In HIV-infected patients, the
      sensitivity and specificity of RCS in differentiating TBM from CM were 86.6% and
      27.7%, respectively, and the area under the ROC curve was 0.669 (0.48-0.85).
      Conclusion: This easy-to-use RCS was found to be helpful in differentiating TBM
      from VM, with a better sensitivity than molecular amplification techniques and a
      relatively good specificity. However, the RCS was not useful to differentiate
      between TBM and CM in HIV-infected patients.

PMID- 29184337
TI  - Optical Coherence Tomography and Subclinical Optical Neuritis in Longitudinally
      Extensive Transverse Myelitis.
AB  - Objective: The aim is to compare the retinal nerve fiber layer (RNFL) thickness
      of longitudinally extensive transverse myelitis (LETM) eyes without previous
      optic neuritis with that of healthy control subjects. Methods: Over 20 LETM eyes
      and 20 normal control eyes were included in the study and subjected to optical
      coherence tomography to evaluate and compare the RNFL thickness. Result:
      Significant RNFL thinning was observed at 8 o'clock position in LETM eyes as
      compared to the control eyes (P = 0.038). No significant differences were seen in
      other RNFL measurements. Conclusion: Even in the absence of previous optic
      neuritis LETM can lead to subclinical axonal damage leading to focal RNFL
      thinning.

PMID- 29184339
TI  - Bone Health in Patients with Epilepsy: A Community-based Pilot Nested Case
      control Study.
AB  - Background: Antiepileptic drugs (AEDs) adversely affect bone health and there are
      reports describing association of alternations of bone and mineral metabolism in
      epileptic patients. Objectives: This study was undertaken to evaluate the bone
      profile (bone mineral parameters and bone mineral density [BMD]) of patients with
      epilepsy and compare them to their age-, gender-, and socioeconomic status
      matched healthy controls in a community. Materials and Methods: This was a nested
      case-control study conducted in fifty individuals, which included 25 cases (age
      above 18 years and on AEDs for at least 3 years) for which 25 controls were
      selected from the same community. Bone mineral parameters (serum calcium,
      proteins, phosphorous, alkaline phosphate, parathyroid hormone, and Vitamin D)
      and BMD were measured. Results: There was significant hypocalcemia (P = 0.003),
      hypoproteinemia (P = 0.014), hyperparathyroidism (P = 0.048), and increased
      levels of serum alkaline phosphatase (P = 0.019) in cases as compared to
      controls. The difference was insignificant in the serum levels of Vitamin D and
      phosphorous among both the groups. Vitamin D was significantly low in female
      patients as compared to males (P = 0.043). There was no significant difference in
      BMD at the lumbar spine and femur neck among both the groups. Mean duration of
      epilepsy was longest in patients with osteoporosis (23.6 years), and increasing
      duration of epilepsy was associated with reduction in age- and sex-corrected
      total BMD mean Z-score anteroposterior spine. There was negative correlation
      between cumulative drug load and T-score of patients with epilepsy. Conclusion:
      Patients on long-term AED treatment have altered bone profile as evident from
      biochemical parameters and reduced BMD. There is a need for more extensive
      research and that too on a larger sample size.

PMID- 29184340
TI  - Treatment-related Fluctuations in Guillain Barre Syndrome and the Conundrum of
      Additional Cycles of Plasmapheresis.
AB  - Introduction: In Guillain Barre syndrome (GBS), worsening of weakness or
      disability after initial period of recovery or stabilization is described as
      treatment-related fluctuations (TRF). Aim: This study aims to describe the
      clinical characteristics and outcome of six patients with GBS and TRF. Patients
      and Methods: Six patients with GBS fulfilling NINCDS criteria, evaluated at a
      tertiary care university hospital during 2008-2017, were diagnosed to have TRF.
      They form the basis of this report. Results: All patients were men and their mean
      age was 40 years. At presentation, mean duration of illness was 15 days; the
      illness had plateaued in three and progressive in other three patients. Two of
      the four patients had variant GBS. Initially, five patients were treated with
      large volume plasmapheresis (LVPP) and one patient with methyl prednisolone. At
      17-28 days after disease onset, three patients developed new neurologic deficits
      (bilateral facial paresis in two; paralytic ileus in one). Other three patients
      with worsening of limb weakness (medical research council sum score of >5) and
      disability (Hughes disability grade by >=1) fulfilled Kleyweg's criteria for TRF.
      All the six patients were treated with the completion of five cycles or
      additional cycles of LVPP. Conclusion: Awareness about TRF is essential for
      correct diagnosis and management of patients with GBS.

PMID- 29184341
TI  - Atherosclerotic Carotid Plaques: Multimodality Imaging with Contrast-enhanced
      Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.
AB  - Introduction: The imaging of carotid plaques has undergone a paradigm shift
      increasing importance being given to plaque characterization. Patients with
      "vulnerable" plaques are more prone to develop future neurovascular events.
      Purpose: The purpose of this study is to analyze the role of multimodality
      imaging techniques in the assessment of carotid atherosclerotic plaques.
      Materials and Methods: Twenty-six patients were prospectively enrolled in the
      study. Patients underwent multidetector computed tomography (CT) angiography,
      ultrasound, contrast-enhanced ultrasound, and high-resolution magnetic resonance
      imaging (MRI) of the carotid arteries with special emphasis on the carotid
      bifurcation. Results: The mean age of patients was 65.41 years. Twenty-one were
      males. Plaque neovascularization was seen in 10 of the 18 plaques studied
      (55.56%). Based on the predominant components of the plaque, plaques were
      characterized as lipid (3), lipid with recent hemorrhage (1), fibrous (7),
      fibrofatty (4), fibrofatty with some hemorrhagic components (3), and recent
      hemorrhage (2). Conclusions: Together, contrast-enhanced ultrasound, CT, and MRI
      provide complete information about the plaque characteristics.

PMID- 29184342
TI  - Risk Factors, Vascular Lesion Distribution, Outcome and Recurrence of Strokes Due
      to Intracranial Atherosclerosis: One Year Data from Hyderabad Stroke Registry.
AB  - Background: Intracranial atherosclerotic stenosis (ICAS) is a common cause of
      ischemic stroke in Asian countries and probably in India. Aim: The aim of this
      study was to describe the risk factors, distribution of vascular lesions,
      recurrence and outcome of stroke due to ICAS. Methodology: A total of 100
      consecutive patients of ischemic stroke due to ICAS were enrolled prospectively
      from January 1, 2015, to December 31, 2015, and followed for 1 year for treatment
      compliance and recurrence. The details about demographics, risk factors, and
      vascular lesions were noted. Results: There were 68 males and 32 females.
      Hypertension (HTN), diabetes, alcohol, smoking, hyperlipidemia, and
      hyperhomocysteinemia was present in 82%, 52%, 34%, 33%, 28%, and 23%,
      respectively. The number of arteries involved were middle cerebral artery, 53
      (37.3%); posterior cerebral artery, 24 (16.9%); internal cerebral artery, 21
      (14.8%); vertebral artery, 18 (12.7%); basilar artery, 6 (4.2%); and anterior
      cerebral artery, 6 (4.2%). Seventeen (17%) patients had a recurrent stroke during
      1 year follow-up. The presence of uncontrolled HTN and diabetes mellitus after
      discharge were significantly associated with stroke recurrence (P < 0.05). The
      use of dual antiplatelet agents and statins was found to have a significant
      effect in the prevention of recurrent stroke (P < 0.05). Severe stroke at
      presentation and presence of hemiparesis were the predictors for unfavorable
      outcome at 3 months (P < 0.05). Conclusion: Risk factors, distribution of
      vascular lesions and high recurrence of stroke due to ICAS in this study is
      similar to that reported from other Asian countries. Aggressive medical
      management and risk factor control remains the best strategy for preventing
      recurrence.

PMID- 29184343
TI  - Quality Indicators of Intravenous Thrombolysis from North India.
AB  - Background: Data on intravenous (IV) thrombolysis using tissue plasminogen
      activator (tPA) are limited from low- and middle-income countries. We aimed to
      assess the quality indicators of IV thrombolysis in our stroke unit. Methods: All
      stroke patients admitted in our hospital from October 2008 to April 2017 were
      included in this study. Data were collected prospectively by trained research
      staff in a detailed case record form. Outcome was assessed using modified Rankin
      Scale (mRS, 0-1 good outcome). Results: Of the total 4720 stroke patients seen,
      944 (20%) came within window period (<4.5 h). Of these, 214 (4.5%) were eligible
      for thrombolysis and 170 (3.6%) were thrombolysed, relatives of 23 (23/214,
      10.7%) patients denied consent, and 21 (9.8%) patients could not afford tPA. The
      mean age of thrombolysed patients was 58.4 (range 19-95) years. Median NIHSS at
      admission was 12 (interquartile range 2-24). Average onset-to-door (O-D) time was
      76.8 (5-219) min, door-to-examination (D-E) time was 17.8 (5-105) min, door-to-CT
      (D-CT) time was 48 (1-205) min, and door-to-needle (D-N) time was 90 (20-285)
      min. At 6 months, 110 (64.7%) patients were contactable and 82 (74.5%) patients
      had good outcome (mRS 0-1). Conclusion: Thrombolysis rate has steadily increased
      at the center without undue adverse effects even in the elderly. D-E and D-CT
      times have reduced, but O-D and D-N times need further improvement. More patients
      could be thrombolysed if the cost of tPA is reduced and the consent process is
      waived.

PMID- 29184344
TI  - Nocardia Farcinica Brain Abscess in an Immunocompetent Old Patient: A Case Report
      and Review of Literature.
AB  - By definition, a brain abscess is an intraparenchymal collection of pus. Nocardia
      shows to have a special tropism for the neural tissue. Solitary abscess
      represents the most common manifestation in the central nervous system,
      accounting for 1%-2% of all cerebral abscesses. In this report, we present a case
      of primary multiple brain abscesses due to Nocardia farcinica in an immune
      competent patient. Early diagnosis and surgical intervention is significant for
      the patient.

PMID- 29184345
TI  - Vagus Nerve Stimulation Modulates Complexity of Heart Rate Variability
      Differently during Sleep and Wakefulness.
AB  - Progressive loss of heart rate variability (HRV) and complexity are associated
      with increased risk of mortality in patients with cardiovascular disease and are
      a candidate marker for patients at risk of sudden cardiac death. HRV is
      influenced by the cardiac autonomic nervous system (ANS), although it is unclear
      which arm of the ANS (sympathetic or parasympathetic) needs to be perturbed to
      increase the complexity of HRV. In this case-control study, we have analyzed the
      relation between modulation of vagus nerve stimulation (VNS) and changes in
      complexity of HRV as a function of states of vigilance. We hypothesize that VNS -
      being a preferential activator of the parasympathetic system - will decrease the
      heart rate (HR) and increase the complexity of HRV maximum during sleep. The
      electrocardiogram (EKG) obtained from a 37-year-old, right-handed male with known
      intractable partial epilepsy and left therapeutic VNS was analyzed during
      wakefulness and sleep with VNS ON and OFF states. Age-matched control EKG was
      obtained from five participants (three with intractable epilepsy and two without
      epilepsy) that had no VNS implant. The study demonstrated the following: (1) VNS
      increased the complexity of HRV during sleep and decreased it during wakefulness.
      (2) An increase in parasympathetic tone is associated with increased complexity
      of HRV even in the presence of decreased HR. These results need to be replicated
      in a larger cohort before developing patterned stimulation using VNS to stabilize
      cardiac dysautonomia and prevent fatal arrhythmias.

PMID- 29184346
TI  - Cutaneous Adverse Drug Reactions to Lamotrigine and Human Leukocyte Antigen
      Typing in North Indian Patients: A Case Series.
AB  - Cutaneous adverse drug reaction (cADR) has limited epidemiological data in India.
      The older antiepileptic drugs, i.e., carbamazepine, phenytoin, valproic acid,
      phenobarbitone, etc., induce severe cADRs that have a strong associated with
      human leukocyte antigen (HLA)-related genetic risk factors. There is also
      evidence of association of certain HLA alleles with lamotrigine (LTG)-induced
      cADRs, but this has not been reported in the Indian population. Here, we report
      case series of three patients with LTG-induced "Stevens-Johnson syndrome (SJS)."
      Their HLA-B typing was also performed which showed the presence of HLA-B*15:02 in
      one case with SJS.

PMID- 29184347
TI  - Anti Myelin Oligodendrocyte Glycoprotein associated Immunoglobulin G (AntiMOG
      IgG)-associated Neuromyelitis Optica Spectrum Disorder with Persistent Disease
      Activity and Residual Cognitive Impairment.
AB  - Antibodies targeting myelin oligodendrocyte glycoprotein (MOG) have been recently
      reported in association with idiopathic inflammatory central nervous system
      disorders. Initially believed to be a benign disorder, anti MOG-IgG was noted to
      cause steroid responsive recurrent optic neuritis and isolated longitudinally
      extensive myelitis. However, there is growing evidence that the disease may be
      predominantly relapsing, often producing severe visual loss and involving regions
      other than the spinal cord and optic nerve. We report an adolescent male with an
      aggressive disease course previously undescribed in anti MOG-IgG-associated
      disease that left him with residual cognitive dysfunction.

PMID- 29184349
TI  - A Rare Presentation of A Nondiscogenic Cause of Acute Lumbar Radiculopathy.

PMID- 29184348
TI  - Subdural Empyema in Disseminated Histoplasmosis.

PMID- 29184350
TI  - Female Caregivers and Stroke Severity Determines Caregiver Stress in Stroke
      Patients.
AB  - Background: Stroke is among the major causes of short- and long-term disability.
      This study aimed to understand the caregivers (CGs) stress in stroke survivors.
      Materials and Methods: A 22-item questionnaire was administered to 201 CGs of
      stroke survivors. The variables tested were physical and mental health, social
      support, financial, and personal problems. CGs were divided into Group A (Barthel
      index [BI] <75) and B (BI >75) according to patient's BI, according to gender
      (male and female CG) and relation; spouses (wife, husband), daughters, sons,
      daughter-in-law, grandchildren, and rest (father, mother, brother, sister, and in
      laws). Data were analyzed using SPSS software version-21. Data were analyzed to
      determine which variables of the patient effects the CG stress. Results: Majority
      of the CGs (74.62%) were females. 65% of CGs graded their burden as moderate to
      severe. 81% of CGs had left their work for caregiving. More than half of the CGs
      felt sleep disturbance and physical strain. Psychological instability and
      financial burdens were reported in 3/4th of CGs. Group A CGs faced more sleep,
      financial, health, and social life disturbance. Patient's bladder and bowel
      problems, shoulder pain, patients noncooperative attitude for medication
      administration, and physiotherapy were more upsetting for Group A CGs. Female CGs
      were subjected to more sleep disturbance, physical and psychological stress,
      faced more difficulty regarding the patient's bladder, bowel, personal hygiene
      needs, and physiotherapy. Female CGs felt less motivated in caregiving than male
      CGs. Wives and daughters-in-law experienced more burden. Time spent and burden
      perceived was more by female CGs (chi2 = 15.199, P = 0.002) than males (chi2 =
      11.931, P = 0.018); wives and daughters than other relations (chi2 = 32.184, P =
      0.000), (chi2 = 35.162, P = 0.019). Conclusion: Our study showed that caregiving
      burden was predominantly shouldered by females CGs. CGs faced physical,
      psychological, and socioeconomic burden. The burden was more evident in female
      CGs and in patients with severe stroke.

PMID- 29184351
TI  - Clinico-Electrophysiological and Genetic Overlaps and Magnetic Resonance Imaging
      Findings in Charcot-Marie- Tooth Disease: A Pilot Study from Western India.
AB  - Background: Charcot-Marie-Tooth (CMT) disease is clinically and genetically
      heterogeneous. There are no published series describing clinical,
      electrophysiological, and genetic information on CMT from the Indian
      subcontinent. Magnetic resonance imaging (MRI) neurography technique provides
      useful information about the plexus and roots and can be employed in patients
      with CMT. Settings and Design: A prospective, observational study carried out at
      a tertiary care hospital in Western India. Subjects and Methods: CMT patients
      fulfilling the UK Genetic Testing Network criteria were included. They underwent
      clinical, electrophysiological, radiological, and multigene panel testing.
      Results: Totally 22 patients (19 males, 3 females; 18 sporadic and 4 familial
      cases) were studied. Pes cavus (19), hammer toes (16), and scoliosis was seen in
      1 patient. Electrophysiology revealed motor predominant neuropathy with 15
      demyelinating (10 uniform and 5 multifocal) and 7 axonal patterns. Thickened
      lumbosacral plexuses on MRI neurography were evident in 6/10 studied patients,
      all 6 having demyelinating neuropathy. Genetic analysis identified PMP22, GJB1,
      SH3TC2, HSPB1, SPTLC2, MPZ, AARS, and NEFH gene mutations. Conclusions: This
      small series documents the pattern of CMT neuropathies as seen in Western India.
      Clinico-electrophysiological and genetic diagnosis showed general concordance
      some overlaps and reiterated advantages of gene panel testing in this
      heterogeneous group of neuropathies. MRI neurography was useful as an additional
      investigation to detect nerve enlargement in patients with demyelinating
      neuropathies.

PMID- 29184352
TI  - Subcutaneous Injection of Botulinum Toxin-A in Postherpetic Neuralgia During
      Pregnancy.

PMID- 29184353
TI  - Simultaneous Miliary Lesions of Brain and Lungs: A Diagnostic Challenge.

PMID- 29184354
TI  - Carbamazepine-induced Seizure in a Nonepileptic Child.

PMID- 29184355
TI  - A Sibling Pair with Autosomal Recessive Charcot-Marie-Tooth Disease Due to Novel
      Ganglioside-induced Differentiation-associated Protein 1 Mutation.

PMID- 29184356
TI  - Parkinsonism and Tremor Complicating Long-term Cinitapride Use.

PMID- 29184357
TI  - Refractory Myasthenia Gravis Treated Successfully with Rituximab: A Case Report.

PMID- 29184358
TI  - Spinocerebellar Ataxia Type 7 Sans Retinal Degeneration: A Phenotypic
      Variability.

PMID- 29184359
TI  - Identification of non-cerebral cyst: Zoonotic Taenia multiceps in domestic goat
      in Bangladesh.
AB  - Aim: This study was performed to identify the non-cerebral Taenia multiceps cyst
      through molecular phylogeny of the 12S rRNA gene. Materials and Methods: Eight
      cyst samples were collected from 385 examined slaughtered goats during October
      2015-September 2016 from three slaughterhouses in Chittagong City Corporation.
      Cysts were removed from the thigh muscle, and scolices were collected for light
      microscopic examination and molecular identification. The DNA was extracted and
      analyzed by polymerase chain reaction using 12S rRNA gene primers. Cyst samples
      were also preserved in 10% buffered formalin for histopathological study.
      Results: T. multiceps non-cerebral cyst is 2.1% prevalent in goat in this area.
      Under light microscopic examination, scolex was found with four suckers and a
      rostellum with the double crown of 32 hooks and hooklets. Molecularly, all the
      samples were amplified with 12S rRNA gene fragments yielded 270 base pair
      amplicon. Zenker's necrosis with focal to diffuse infiltration of lymphocytes and
      eosinophil was also found around the cyst wall in histopathological examination.
      Conclusion: Although the non-cerebral form of the cysts produced by T. multiceps
      is genetically identical with the cerebral cyst, previously published data
      indicated that cerebral T. multiceps cyst is predominant in other parts of the
      world as well as in Bangladesh. This study showed that non-cerebral cyst is also
      prevalent in this country which is very important for public health concern. This
      study depicts an idea of non-cerebral form of zoonotic T. multiceps cyst which
      will be helpful in taenia cyst control and prevention.

PMID- 29184360
TI  - Serological investigation of some important RNA viruses affecting sheep and goats
      in Giza and Beni-Suef governorates in Egypt.
AB  - Aim: The aim of this study was to investigate the seroprevalence of antibodies
      against foot and mouth disease (FMD), Peste des Petits ruminants (PPR), and
      bluetongue (BT) in sheep and goats within Giza and Beni-Suef governorates at the
      second half of 2016. Materials and Methods: A total of 300 animals (sheep and
      goats) randomly selected from small stocks with no history of previous
      vaccination against FMD virus (FMDV), PPR, or BT viruses (BTV) and examined with
      competitive enzyme-linked immunosorbent assay for detection of FMD-non-structural
      protein, PPR, and BT antibodies. Results: Seroprevalence analysis revealed that
      antibodies against FMDV were 40.8% and 37.1% at Giza governorate, while at Beni
      Suef governorate, the percent was 36.7% and 50% in sheep and goat, respectively.
      Antibodies against PPR were 63.8% in sheep and 45.7% in goats at Giza
      governorate, whereas the results for Beni-Suef governorate were 71.7% in sheep
      and 45% in goats. Antibodies against BT were 45% and 37% in sheep and goats,
      respectively, in Giza governorate, whereas the results for Beni-Suef governorate
      were 80% and 55% in sheep and goats, respectively. The average of BTV antibody
      prevalence was significantly higher in sheep (45% and 80%) than in goats (37% and
      55%) in Giza and Beni-Suef, respectively. Statistical analysis for the three
      viruses showed the high relation between the two governorates in case of sheep
      (r=0.85) and in case of goats (r=0.87). In general, a strong positive correlation
      was observed between the governorates (r=0.93). Conclusion: Giza and Beni-Suef
      governorates are endemic with FMDV, PPR, and BTV. Regional plan for
      characterization and combating FMD, PPR, and BT is recommended to help in the
      achievement of the most suitable combination of the vaccine regimen.

PMID- 29184361
TI  - Phenotypic and genotypic characterization of antimicrobial susceptibility of
      avian pathogenic Escherichia coli isolated from broiler chickens.
AB  - Aim: Avian pathogenic Escherichia coli (APEC) is pathogenic strains of E. coli
      that are responsible for one of the most common bacterial diseases affecting
      poultry worldwide. This study was designed to determine the occurrence,
      antibiotic resistance profile, and antibiotic resistance genes of E. coli
      isolated from diseased and freshly dead broilers. Materials and Methods: In that
      context, a total of 200 broilers samples were examined by standard
      microbiological techniques for isolation of E. coli, and tested for their
      antimicrobial susceptibility against 15 antimicrobial agents using disc diffusion
      method. In addition, E. coli isolates were screened by multiplex polymerase chain
      reaction for detection of a number of resistance genes including aadA1 gene
      encodes streptomycin/neomycin, tetA encodes resistance to tetracycline, sul1
      encodes sulfonamides, and beta-lactamase encoding genes (blaTEM and blaSHV).
      Results: A total of 73 (36.5%) isolates were biochemically identified as E. coli
      strains. O78, O2, and O1 are the most prevalent serotypes detected. E. coli
      displayed a high resistance against penicillin (100%), followed by cefepime
      (95.8%) and a low resistance to norfloxacin (36.9%), and chloramphenicol (30%).
      Depending on the results of PCR, sul1 gene was the most predominant antibiotic
      resistant gene (87%) followed by blaTEM (78%), tetA genes (60%), and aadA (54%).
      However, blaSHV had the lowest prevalence (23%). Conclusion: The obtained results
      demonstrated the importance of studies on APEC and antibiotic resistance genes in
      our region which associated with intensive poultry industry, aiming to acquire
      preventive measures to minimize losses due to APEC and associated multidrug
      resistance and resistance genes that of high significance to the rational use of
      antibiotics in clinical and public health.

PMID- 29184362
TI  - Analysis of spatial dynamic of epizootic process of bluetongue and its risk
      factors.
AB  - Aim: The study was undertaken to find out the spatial dynamic occurrence and
      patterns of the global spread of bluetongue (BT) disease for the period from 1996
      to 2016, as well as the assessment of the risk of occurrence and its spread in
      2017-2018. Materials and Methods: Outbreaks (serum samples were collected from
      clinically healthy as well as suspected animals in infected points) were
      confirmed and reported officially by veterinary departments which represent
      different geographical regions in the world to World Organization for Animal
      Health. These reports explained that ELISA and polymerase chain reaction were
      used to identify the BT disease, taking in the account number of infected, dead
      animals, and focus of BT infection in all susceptible animals from 1996 to 2016.
      Once conventional statistical population was defined (an observational study), we
      had classified data as well as possible to answer to our aim, using descriptive
      statistics methods, including the test of the relationship between different
      epizootiological indicators. Results: The spatial dynamic study of BT's
      occurrence and its spread in the world over the two past decades was presented by
      different epizootic indicators. The given analysis includes assessment and
      measurement of risk factors. It was built too, regression models, and allowed to
      put different forecasts on the different epizootic indicators in the years 2017
      2018 by the extrapolation method. We had also determined that, in 2017, BT
      continues to spread with the total expectancy of 3.4 focus of infection (number
      of diseased animals in a single unfavorable point) and mortality of about 26 %;
      these rates tend to decrease in 2018. At abused points by BT, up to 78.4% of
      animals are mixed (more than one type) and in 21.6% - uniform. By this way, the
      relative risk of the incidence of appearance-abused points in mixed households
      has 3.64, which might be considered higher for the BT dissemination. Moreover,
      between the enzootic index and other epizootiological indicators had revealed an
      inverse correlation, i.e., to an increase in the level of enzootic index among
      the cattle population would be formed population less sensitive to BT. Cluster
      analysis was done, which had demonstrated the zoning of risk levels in the world
      and the occurrence of the disease intensity in the period 1996-2016 years. Then,
      assess connection degree of the dynamic of BT tension with geographical and
      socioeconomic conditions background 0.66 and 0.68, respectively. Conclusion: It
      is important to define a variety of BT risk factors and assess their influence on
      BT occurrence. However, the most important is to define the overlapping
      coinfluence between them that cause serious losses. To have an out of BT
      territory needs to make an emphasis of co-influence of risk factors on this zone.
      Was predicted a continue hits of disease in the next year with weight moderation
      through one year. Far from statists, to assess the given forecast may have a
      serious variety, taken in account problems of actual climate change in the world.

PMID- 29184363
TI  - Effect of antioxidants supplementation on the quality of Beetal buck semen stored
      at 4 degrees C.
AB  - Aim: An experiment was designed to evaluate the role of Vitamin E and glutathione
      in improving the seminal parameters during hypothermic storage of liquid semen at
      4 degrees C for 72 h. Materials and Methods: Thirty-six semen ejaculates were
      collected by artificial vagina from 6 bucks (Beetal) during the normal
      reproduction season (September to November) at weekly interval. The samples were
      centrifuged, and the seminal plasma was removed. The sperm pellet was diluted
      with Tris-based extender and divided into three groups. Group T1: Control samples
      without antioxidants, Group T2: Samples supplemented with tocopherol at 3 mM, and
      Group T3: Samples supplemented with glutathione at 1 mM. The samples were
      evaluated for progressive motility, percent liveability, percent abnormal
      spermatozoa, and acrosome integrity after liquid preservation for 0, 24, 48, and
      72 h. The level of lipid peroxidation and antioxidant enzymes, namely,
      glutathione peroxidase (GPx) and superoxide dismutase (SOD) were estimated after
      liquid preservation for 0 and 72 h. Results: It was observed that, after storage
      of semen at 4 degrees C up to 72 h, the progressive sperm motility, percent
      liveability, percent abnormal spermatozoa, and percent intact acrosomes were
      significantly (p<0.05) higher in group T2 and T3 samples as compared to control.
      However, the level of lipid peroxidation in T2 and T3 groups was significantly
      (p<0.05) lower after 72 h of incubation at 4 degrees C. Similarly, GPx and SOD
      values were significantly (p<0.05) increased in T2 and T3 groups after 72 h of
      storage at 4 degrees C. Conclusion: Thus, it can be concluded that Vitamin E and
      glutathione supplementation at 3 mM and 1 mM, respectively, while preserving the
      semen samples at 4 degrees C helped in maintaining the seminal parameters up to
      72 h and protected the spermatozoa from oxidative damage.

PMID- 29184364
TI  - Seroprevalence of Fasciolagigantica infection in bovines using cysteine
      proteinase dot enzyme-linked immunosorbent assay.
AB  - Aim: The objective of the present study was to know the seroprevalence status of
      Fasciola gigantica infection in cattle and buffaloes using cysteine proteinase
      (CP) antigen in dot enzyme-linked immunosorbent assay (ELISA) format under field
      conditions. Materials and Methods: As per the standard protocol, the sera were
      collected from the blood of 112 cattle and 38 buffaloes of coastal areas of
      Navsari district, South Gujarat, India. The indirect ELISA was performed on the
      strip of nitrocellulose paper blotted with 1 ul of CP antigen, to detect F.
      gigantica seropositive animals. Results: The native CP of F. gigantica revealed a
      single visible band on 10% sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. There was no any noted cross-reaction between the selected
      antigen and sera of Gastrothylax crumenifer-infected animals in ELISA. Out of 150
      screened bovines, the sera of 47 (31.33%) were found to be reactive in dot-ELISA,
      with a prevalence rate of 31.25% and 31.58% in cattle and buffaloes,
      respectively. The seropositive bovines with heavy, moderate, and light level of
      infection were 44.68%, 34.04%, and 21.28%, respectively (p<0.05 between heavy and
      light; p>0.05 between moderate and heavy or light). The share of F. gigantica
      seropositive and negative animals was 31% and 69%, respectively. The optical
      density at 450 nm of pooled sera of seropositive bovines with heavy, moderate,
      and light reactivity in plate-ELISA was significantly higher with field or
      reference -negative sera. Conclusion: The CP-based dot-ELISA can be useful for
      field veterinarians for quick and timely isolation of the animals requiring
      urgent flukicide therapy.

PMID- 29184365
TI  - Public health concerns of highly pathogenic avian influenza H5N1 endemicity in
      Africa.
AB  - Highly pathogenic avian influenza virus (HPAIV) H5N1 was first officially
      reported in Africa in 2006; thereafter this virus has spread rapidly from Nigeria
      to 11 other African countries. This study was aimed at utilizing data from
      confirmed laboratory reports to carry out a qualitative evaluation of the factors
      responsible for HPAI H5N1 persistence in Africa and the public health
      implications; and to suggest appropriate control measures. Relevant publications
      were sought from data banks and repositories of FAO, OIE, WHO, and Google
      scholars. Substantiated data on HPAI H5N1 outbreaks in poultry in Africa and in
      humans across the world were mined. HPAI H5N1 affects poultry and human
      populations, with Egypt having highest human cases (346) globally. Nigeria had a
      reinfection from 2014 to 2015, with outbreaks in Cote d'Ivoire, Ghana, Niger,
      Nigeria, and Burkina Faso throughout 2016 unabated. The persistence of this virus
      in Africa is attributed to the survivability of HPAIV, ability to evolve other
      subtypes through genetic reassortment, poor biosecurity compliance at the live
      bird markets and poultry farms, husbandry methods and multispecies livestock
      farming, poultry vaccinations, and continuous shedding of HPAIV, transboundary
      transmission of HPAIV through poultry trades; and transcontinental migratory
      birds. There is, therefore, the need for African nations to realistically
      reassess their status, through regular surveillance and be transparent with HPAI
      H5N1 outbreak data. Also, it is important to have an understanding of HPAIV
      migration dynamics which will be helpful in epidemiological modeling, disease
      prevention, control and eradication measures.

PMID- 29184366
TI  - Polymerase chain reaction detection of genes responsible for multiple antibiotic
      resistance Staphylococcus aureus isolated from food of animal origin in Egypt.
AB  - Aim: The aim of our study was polymerase chain reaction (PCR) detection of the
      genes responsible for the multiple antibiotic resistance S. aureus isolated from
      food of animal origin in Egypt. Materials and Methods: A total of 125 samples
      were randomly collected from milk, meat, and their products from Giza and Beni
      Suef Governorates markets. The S. aureus isolates were subjected to antimicrobial
      sensitivity tests using four antibacterial disks (Oxoid), and then the polymerase
      chain reaction (PCR) was performed for detection of antibiotic resistance genes.
      Results: Out of 125 samples, 19 S. aureus isolates were detected. All detected
      isolates were multiple drug resistance (MDR). The penicillin-, erythromycin-,
      kanamycin-, and tetracycline-resistant isolates were examined by PCR for
      resistance genes blaZ, (msrA, ermB, and ermC), aac(6')aph (2"), and tetK. The
      isolates harbored these resistance genes with percentage of 100% (100%, 0%, and
      100%), 62.5%, and 100%, respectively. Conclusion: Contaminated foods of animal
      origin may represent a source of MDR S. aureus that can be a major threat to
      public health.

PMID- 29184367
TI  - Protective efficacy of combined trivalent inactivated ISA 71 oil adjuvant vaccine
      against avian influenza virus subtypes (H9N2 and H5N1) and Newcastle disease
      virus.
AB  - Aim: The objective of the present study was to prepare a trivalent inactivated
      vaccine of Newcastle disease virus (NDV), H5N1, and H9N2 viruses. Materials and
      Methods: Three monovalent and a trivalent vaccines were prepared by emulsifying
      inactivated NDV (LaSota strain), reassortant H5N1, and H9N2 viruses with
      Montanide ISA 71 oil adjuvant. Parameters used for evaluation of the efficacy of
      the prepared vaccines in specific pathogen-free chickens were cellular immunity
      assays (blastogenesis, interferon gamma, interleukin 1 [IL1], and IL6), humoral
      immunity by hemagglutination inhibition, protection percentage, and shedding.
      Results: A single immunization with trivalent vaccine-enhanced cell-mediated
      immunity as well as humoral immune response with 90% protection against
      challenges with highly pathogenic avian influenza (HPAI) H5N1 and low pathogenic
      (LP) avian influenza H9N2 viruses with 100% protection after challenge with NDV.
      Conclusion: Development and evaluation of the trivalent vaccine in the study
      reported the success in preparation of a potent and efficacious trivalent vaccine
      which is a promising approach for controlling HPAI H5N1, LP H9N2, and ND viral
      infections.

PMID- 29184368
TI  - West African donkey's liveweight estimation using body measurements.
AB  - Aim: The objective of this study was to determine a formula for estimating the
      liveweight in West African donkeys. Materials and Methods: Liveweight and a total
      of 6 body measurements were carried out on 1352 donkeys from Burkina Faso, Mali,
      Niger, and Senegal. The correlations between liveweight and body measurements
      were determined, and the most correlated body measurements with liveweight were
      used to establish regression lines. Results: The average weight of a West African
      donkey was 126.0+/-17.1 kg, with an average height at the withers of 99.5+/-3.67
      cm; its body length was 104.4+/-6.53 cm, and a heart girth (HG) of 104.4+/-6.53
      cm. After analyzing the various regression lines and correlations, it was found
      that the HG could better estimate the liveweight of West African donkeys by
      simple linear regression method. Indeed, the liveweight (LW) showed a better
      correlation with the HG (R2=0.81). The following formulas (Equations 1 and 2)
      could be used to estimate the LW of West Africa donkeys.Equation 1: Estimated LW
      (kg) = 2.55 * HG (cm) - 153.49. Conclusion: The above formulas could be used to
      manufacture weighing tape to be utilized by veterinary clinicians and farmers to
      estimate donkey's weight in the view of medication and adjustment of load.

PMID- 29184369
TI  - Clinicopathological alterations in naturally occurring Babesia gibsoni infection
      in dogs of Middle-South Gujarat, India.
AB  - Aim: The present research work was undertaken to describe various clinical signs
      and hematobiochemical alterations in dogs affected with Babesia gibsoni.
      Materials and Methods: Blood smears from a total of 79 suspected dogs of Anand
      region as well as Surat region of Gujarat state (India) were screened for
      detection of intraerythrocytic piroplasm of small form of Babesia. Diagnosis was
      made on the basis of clinical signs and demonstration of B. gibsoni organism in
      Giemsa-stained thin blood smears. The clinical signs were recorded at the time of
      presentation, and blood samples were subjected to estimation of hematobiochemical
      parameters by auto hematology analyzers at College of Veterinary Science and
      Animal Husbandry, Anand. Statistical analysis, interpretation, and comparison of
      hematobiochemical changes with scientific literature were carried out to
      understand the pathophysiology of the disease. Results: Out of 79 dogs, 16 were
      positive for naturally occurring babesiosis based on the presence of
      intraerythrocytic piroplasm of small form of Babesia in blood smears. The
      clinical cases were manifested by wide variety of non-specific clinical signs.
      The hematological evaluation revealed that the mean values of hemoglobin and
      total erythrocyte counts in dogs with babesiosis decreased significantly (p<0.01)
      in comparison to healthy dogs. Among differential leukocyte count, mean values of
      neutrophils and eosinophils increased while lymphocytes decreased (p<0.01) in
      dogs with babesiosis in comparison to healthy dogs. Serum biochemistry revealed
      increase (p<0.01) value of alkaline phosphatase, alanine aminotransferase,
      aspartate aminotransferase, and globulin as well as decrease in albumin levels
      (p<0.05) in dogs with babesiosis as compared to healthy dogs. Conclusion: B.
      gibsoni is having multisystemic effects with atypical hematobiochemical changes
      in dog are discussed here, which would aid new insights in diagnosis of disease.

PMID- 29184371
TI  - Epidemiology of bovine fascioliasis in the Nile Delta region of Egypt: Its
      prevalence, evaluation of risk factors, and its economic significance.
AB  - Aim: This study focuses on the risk factors associated with the prevalence of
      Fasciola affecting cattle population in three provinces belonging to the Nile
      Delta of Egypt and to estimate the economic losses as a result of fascioliasis.
      Materials and Methods: From January 2015 to end of December 2015, records of 21
      farms (4976 cattle) were analyzed to screen the prevalence of fascioliasis among
      cattle farms, to identify its associated risk factors and its economic impacts on
      Nile Delta region of Egypt. Results: The overall prevalence of fascioliasis in
      the Nile Delta region of Egypt was 9.77%. The prevalence of fascioliasis was
      found to be statistically significantly associated with age, sex, breed, and type
      of farms. The highest prevalence was observed in <2 age group (10.91%), and the
      lowest was >3 age groups (8.35%). In terms of body condition scores, cattle with
      medium and poor conditions were associated with fascioliasis more than those with
      good body condition. Besides, cattle raised in organic farms were associated with
      lower risk of fascioliasis than those in conventional farms. The prevalence of
      fascioliasis was noted more prominent in districts with moderate temperatures and
      with relative humidity (>60%). The annual overall costs for fascioliasis were
      estimated to be 221.2 USD/cow due to the significant reduction in body weight,
      reduction in milk production, and the treatment costs for fascioliasis.
      Conclusion: The results provided could be helpful for improving the control and
      preventive strategies.

PMID- 29184370
TI  - Occurrence of virulent and antibiotic-resistant Shiga toxin-producing Escherichia
      coli in some food products and human stool in Egypt.
AB  - Aim: Shiga toxin-producing Escherichia coli (STEC) represent a severe public
      health issue worldwide, causing life-threatening diseases in the human
      gastrointestinal tract. This study aimed to determine the occurrence of virulent
      and antibiotic-resistant STEC in retail meat and milk products and human stool
      samples and to characterize the genes encoding for virulence and antibiotic
      resistance among the identified STEC isolates. Materials and Methods: A total of
      260 food samples were randomly collected from retail markets in different
      localities of El Giza Governorate, Egypt. 50 stool specimens were obtained from
      children that had diarrhea at Embaba Fever Hospital. All collected samples were
      initially subjected to bacteriological examination and serotyping, and then
      subsequently, the isolates were exposed to polymerase chain reaction application
      and sequencing for the identification of the virulence-related genes. Finally,
      the virulent STEC isolates were tested for antibiotic susceptibility. Results:
      Serotyping of the 76 biochemically identified isolates showed that 18 were STEC
      with a predominance of non-O157 (16) while 2 O157:K-serotype was detected only in
      one food and one human isolate. Molecular identification of the virulence genes
      illustrated that the minced meat showed the highest prevalence of STEC (8%) as
      compared to the other food products. In the humans, the O157 was the only
      serotype that expresses the Shiga toxin-associated gene (eaeA). Antibiotic
      susceptibility test displayed that 13 of the 17 food and human isolates (76.47%)
      were resistant to cephalothin (KF30). 9 of the 13 cephalothin-resistant isolates
      harbor the beta lactamase (blaTEM )-resistant gene. All isolates were sensitive
      to chloramphenicol, ciprofloxacin, amikacin, and gentamicin. DNA sequencing and
      phylogenetic analysis of the stx2-positive minced meat isolate revealed a high
      genetic relatedness with beef minced meat from the USA and Australia. Conclusion:
      This study showed the predominance of non-O157 among the identified isolates.
      Minced meat showed the highest prevalence of STEC as compared to the other food
      products, and this work illustrates the necessity to consider the food products
      as a potential source of the non-O157 STEC serotypes. DNA sequencing and
      phylogenetic analysis revealed a high genetic relatedness with beef minced meat
      from the USA and Australia. This highlights the high probability of worldwide
      spread of such serotypes, signifying the importance of the one world concept.

PMID- 29184372
TI  - Factors influencing growth hormone levels of Bali cattle in Bali, Nusa Penida,
      and Sumbawa Islands, Indonesia.
AB  - Aim: Bali cattle (Bos javanicus) are an Indonesian's native cattle breed that
      distributed in Asia to Australia. The scientific literature on these cattle is
      scarce. The growth hormone (GH) of Bali cattle is investigated from three
      separated islands, namely, Bali, Nusa Penida, and Sumbawa. Materials and Methods:
      Forty plasma samples were collected from each island, and the GH was measured
      using a commercial enzyme-linked immunosorbent assay kit. The data were analyzed
      based on the origin, sex, and cattle raising practices. Results: We found that
      the GH level (bovine GH [BGH]) of animal kept in stall 1.72+/-0.70 ug/ml was
      higher than free-grazing animal 1.27+/-0.81 ug/ml. The GH level was lower in
      female (1.22+/-0.62 ug/ml) compared to male animals (1.77+/-0.83 ug/ml).
      Conclusion: We conclude that the level of BGH in Bali cattle was low and
      statistically equal from all origins. The different level was related to sex and
      management practices. Further validation is needed through observing the growth
      rate following BGH administration and discovering the inbreeding coefficient of
      the animal in Indonesia.

PMID- 29184373
TI  - Occurrence, treatment protocols, and outcomes of colic in horses within Nairobi
      County, Kenya.
AB  - Aim: The aim of this study was to determine the treatments and their outcomes in
      horses with colic in Nairobi County, Kenya. Materials and Methods: This is a
      retrospective study to determine the occurrence, treatments, pain management, and
      outcomes of colic in horses in Nairobi County. Association between pain
      management protocols and the outcomes of colic with regard to recovery or death
      was also determined. Data collected from four equine practitioners were organized
      manually and given numerical codes as appropriate to facilitate entry into the
      computer. The coded data were entered into Microsoft Excel 2010 and exported to
      StatPlus pro 5.9.8 statistical package for analysis. Simple association tests
      were done between various factors and occurrence of colic. Results: The incidence
      of colic for the 11 years was 3.1%, which constituted 68.0% spasmodic colic,
      27.8% impaction colic, and 4.2% displacement colic. Flunixin meglumine as a
      nonsteroidal anti-inflammatory drug (NSAID) was used as the only pain management
      treatment in 85.3% of the cases, flunixin meglumine and butorphanol as NSAID
      OPIOD combination in 6.4% of the cases, while buscopan as an antispasmodic was
      recorded in 5.9% of the cases mainly in spasmodic colic. Univariate analysis
      revealed simple association between various factors and the type of colic a horse
      was having. There was an association between the type of colic and the decision
      making on the pain management protocol to use, whether single analgesic protocol
      (chi2=22.5, p<0.001) or use of analgesic combinations (chi2=18.3, p<0.001). The
      type of colic strongly influenced the decision for performing nasogastric
      intubation (chi2=265, p<0.001), but performing nasogastric intubation was weakly
      (chi2=4.9, p=0.03) associated with horse recovery from colic. Type of colic also
      strongly influenced the need for the use of metabolic stimulants, particularly
      vitamin B-complex (chi2=99.3, p<0.001). Recovery or death of the horse from colic
      was strongly associated with the type of colic (chi2=250, p<0.001). The
      possibility of recurrence of colic was weakly (chi2=4.6, p=0.04) determined by
      the type of colic, a horse had. Multivariate logistic regression revealed that
      the main cause of death was intestinal displacement and the majority of the
      horses with intestinal displacement died (beta-estimate 2.7, odds ratio=0.07,
      p=0.007) compared to horses that had impaction colic. Conclusion: The incidence
      of colic is 3.1%, and the most common type of colic is spasmodic followed by
      impaction. The most common pain management protocol for colic is NSAIDs, mainly
      flunixin meglumine, followed by flunixin-butorphanol combination. Surgery for
      horses with colic in Nairobi County is not commonly done due to impeding poor
      prognoses. The horse owners tend to prefer euthanasia for such cases.

PMID- 29184374
TI  - Molecular characterization of Escherichia coli recovered from traditional milk
      products in Kashan, Iran.
AB  - Aim: Shiga toxigenic Escherichia coli (STEC) strains as emerging groups of
      foodborne pathogens are responsible for most foodborne illnesses. The aim of this
      study was to determine the antibiotic resistance pattern in STEC isolated from
      traditional milk products and their molecular characterization. Materials and
      Methods: A total of 116 samples were randomly purchased from local markets in
      Kashan, Iran, and evaluated for the occurrence of STEC by culturing and molecular
      methods. The antibiotic resistance of obtained isolates was determined by Kirby
      Bauer method. Furthermore, isolates were assayed for the presence of Shiga toxins
      (stx1 and stx2) and intimin gene (eae). Results: The incidence of E. coli in 60
      ice cream, 30 yoghurt, and 26 cheese samples was 8.33%, 10%, and 11.54%,
      respectively. The findings showed that 11 out of 11 (100%) E. coli had both stx1
      and stx2 while eae gene was not found in E. coli isolated of traditional milk
      products. For E. coli strains carrying stx1 and stx2, highest antibiotic
      sensitive levels were related to trimethoprim/sulfamethoxazole, norfloxacin,
      chloramphenicol, and ciprofloxacin, respectively. Conclusion: The results showed
      relationship between the presence of virulence factors and antimicrobial
      resistance. These results can be used for further studies on STEC as an emerging
      foodborne pathogen.

PMID- 29184375
TI  - Biochemical analysis of some serum trace elements in donkeys and horses in
      Eastern region of Kingdom of Saudi Arabia.
AB  - Aim: Little is known about the serum levels of trace elements in donkeys and
      horses in Saudi Arabia. This study aimed to investigate the levels of some trace
      elements in these two species in the eastern region of Saudi Arabia and to
      compare the obtained results with the reference values. Materials and Methods:
      Seventeen Arabian horses and twenty eight Hassawi donkeys were randomly selected
      for this study. All of the studied healthy animals were kept under a uniform
      feeding protocol without any minerals supplementations. Atomic absorption
      spectrometer is used to estimate the serum concentrations of selenium (Se),
      manganese (Mn), chromium (Cr), copper (Cu), iron (Fe), and zinc (Zn) in the
      analyzed samples. Results: Significant differences between horses and donkeys
      were observed in three of the studied elements (Se, Mn, and Cr). Statistically
      significant differences were found in serum Se and Cr between male and female
      horses. The male donkey showed higher Mn, Cu, and Zn levels than female animals.
      Conclusion: The obtained results of trace element levels in serum of Hassawi
      donkeys and Arabian horses in Saudi Arabia are considered as the first values to
      be published for these breeds. When compared to other animals, the measured
      amounts of Se, Mn, Cr, Cu, Fe, and Zn in the serum of horses and donkey are often
      differed, possibly because of the varying living or feeding conditions. Moreover,
      there were some differences in some of the trace elements concentrations related
      to animal's gender and species (horses and donkeys), which will be considered in
      the interpretation of the laboratory data.

PMID- 29184376
TI  - Bovine origin Staphylococcus aureus: A new zoonotic agent?
AB  - Aim: The study aimed to assess the nature of animal origin Staphylococcus aureus
      strains. The study has zoonotic importance and aimed to compare virulence between
      two different hosts, i.e., bovine and ovine origin. Materials and Methods:
      Conventional polymerase chain reaction-based methods used for the
      characterization of S. aureus strains and chick embryo model employed for the
      assessment of virulence capacity of strains. All statistical tests carried on R
      program, version 3.0.4. Results: After initial screening and molecular
      characterization of the prevalence of S. aureus found to be 42.62% in bovine
      origin samples and 28.35% among ovine origin samples. Meanwhile, the methicillin
      resistant S. aureus prevalence is found to be meager in both the hosts. Among the
      samples, only 6.8% isolates tested positive for methicillin resistance. The
      biofilm formation quantified and the variation compared among the host. A Welch
      two-sample t-test found to be statistically significant, t=2.3179, df=28.103, and
      p=0.02795. Chicken embryo model found effective to test the pathogenicity of the
      strains. Conclusion: The study helped to conclude healthy bovines can act as S.
      aureus reservoirs. Bovine origin S. aureus strains are more virulent than ovine
      origin strains. Bovine origin strains have high probability to become zoonotic
      pathogen. Further, gene knock out studies may be conducted to conclude zoonocity
      of the bovine origin strains.

PMID- 29184377
TI  - Virulence and extended-spectrum beta-lactamase encoding genes in Escherichia coli
      recovered from chicken meat intended for hospitalized human consumption.
AB  - Aim: This study describes the prevalence of Escherichia coli in frozen chicken
      meat intended for human consumption with emphasis on their virulence determinants
      through detection of the virulence genes and recognition of the extended-spectrum
      beta-lactamase (ESBL) encoding genes (blaOXA and blaTEM genes). Materials and
      Methods: A total of 120 frozen chicken meat samples were investigated for
      isolation of E. coli. All isolates were subjected to biochemical and serological
      tests. Eight serotypes isolated from samples were analyzed for the presence of
      various virulence genes (stx1, stx2, and eae A genes) using multiplex polymerase
      chain reaction (PCR) technique. Moreover, the strains were evaluated for the ESBL
      encoding genes (blaTEM and blaOXA). Results: Overall, 11.66% (14/120) chicken
      meat samples carried E. coli according to cultural and biochemical properties.
      The most predominant serotypes were O78 and O128: H2 (21.5%, each), followed by
      O121: H7 and O44: H18. Molecular method detected that 2 strains (25%) harbored
      stx1, 3 strains (37.5%) stx2, and 3 strains (37.5%) both stx1 and stx2, while 1
      (12.5%) strain carried eae A gene. Particularly, only O26 serotype had all tested
      virulence genes (stx1, stx2, and eae A). The results revealed that all examined 8
      serotypes were Shiga toxin-producing E. coli (STEC). The ESBL encoding genes
      (blaTEM and blaOXA) of STEC were detected in 4 (50%) isolates by multiplex PCR.
      The overall incidence of blaTEM and blaOXA genes was 3 (37.5%) and 2 (25%)
      isolates. Conclusion: The present study indicates the prevalence of virulent and
      ESBL-producing E. coli in frozen chicken meat intended for hospitalized human
      consumption due to poor hygienic measures and irregular use of antibiotics.
      Therefore, the basic instructions regarding good hygienic measures should be
      adapted to limit public health hazard.

PMID- 29184378
TI  - Survivin expression in canine spontaneous cutaneous and subcutaneous tumors and
      its prognostic importance.
AB  - Aim: The present study was carried out to know the expression level of survivin,
      an inhibitor of apoptosis protein with an objective to determine its prognostic
      importance in cutaneous and subcutaneous tissue tumors of dogs. Materials and
      Methods: Forty cases of canine cutaneous and subcutaneous tissue tumors on
      histopathological examination revealed various round cell, epithelial, and
      mesenchymal cell tumors. Survivin gene expression was detected in all tumors
      tested by TaqMan real-time polymerase chain reaction assay by comparative cycle
      threshold method. Results: The mean survivin gene expression value of benign
      tumors was 0.94+/-0.63 folds and that of malignant tumors was 18.87+/-5.30 folds.
      Postsurgical follow up of 30 malignant tumor cases revealed death in 8,
      recurrence in 7, and neoplastic free alive status in 15 dogs with mean survivin
      fold difference values of 48.49+/-12.39, 14.63+/-6.37, and 5.034+/-2.27,
      respectively. The mean survivin gene expression value was significantly higher in
      malignant (30 cases, 18.87+/-5.30) compared to benign tumors (10 cases, 0.94+/
      0.63), and it varied between various postsurgical follow-up groups (p<0.05).
      Survival analysis, using survivin gene expression median cutoff value of 3.74 in
      30 malignant tumors, was performed to predict probable survival period in
      malignant cutaneous and subcutaneous tumors of dogs. Conclusions: Results of the
      present study indicated that the expression of survivin in canine cutaneous and
      subcutaneous tumors has prognostic value, and survivin expression greater than
      median cutoff value of 3.74 has a poor prognosis.

PMID- 29184379
TI  - Neurotransmitters and Sodium Channelopathies; Possible Link?
AB  - Investigators from the University of British Columbia, Great Ormond Street
      Hospital for Children, and the National Hospital reported their findings on
      neurotransmitter deficiencies in two patients with mutations in voltage-gated
      sodium genes (SCN2A and SCN8A) discovered by whole exome sequencing.

PMID- 29184380
TI  - Ketogenic Diet in Super-Refractory Status Epilepticus.
AB  - Researchers from the Children's National Health System in Washington, D.C.
      studied the feasibility, rate of complications, and effect on seizures of
      initiating the Ketogenic Diet (KD) in pediatric patients with Super-Refractory
      Status Epilepticus (SRSE).

PMID- 29184381
TI  - Anticonvulsant Medications in Mitochondrial Disease.
AB  - Researchers from Vienna, Austria and Sao Paulo, Brazil studied the known effects
      of anticonvulsant drugs on mitochondria, using a literature search to include
      only references to epilepsy associated with mitochondrial disease, and a specific
      anti-convulsant drug (i.e. levetiracetam) with a specific mitochondrial function
      (i.e. mitochondrial membrane potential).

PMID- 29184382
TI  - Phaco capsulotomy: a technique to prevent the Argentinean Flag Sign.
AB  - The Argentinean Flag Sign is a complication that occurs during capsulorhexis
      construction, in which the capsulorhexis extends to the periphery due to lens
      intumescence. Phaco capsulotomy is a technique in which the phacoemulsification
      tip is used to simultaneously create the initial tear in the anterior capsule and
      remove a portion of the intumescent lens, thereby debulking and relieving
      pressure from the lens and capsule, and preventing the Argentinean Flag Sign. A
      detailed description of the phaco capsulotomy technique is provided, including
      applications and potential complications.

PMID- 29184383
TI  - Prevalence and factors associated with childhood visual impairment in Ethiopia.
AB  - Background: Visual impairment is a significant loss of vision. It has an impact
      on the prosperity of different countries. It has been difficult to plan
      preventive measures against visual impairment due to the scarcity of data about
      the extent of the problem. Objectives: The study was aimed at assessing the
      prevalence and identifying factors associated with visual impairment among school
      age children in Ethiopia. Materials and methods: A cross-sectional study design
      was used in four randomly selected schools found in Addis Ababa from May 15 to
      June 14, 2016. A total of 804 school-age students were selected using the simple
      random sampling method. Bivariable logistic regression and multivariable logistic
      regression were conducted. A p-value <0.05 was taken as a significant
      association. Results: A total of 718 students participated in the study,
      obtaining a response rate of 89.3%. In all, 7.24% of school-age children were
      visually impaired, of whom 3.9% had low vision and 3.34% had severe visual
      impairment. Factors associated with visual impairment were being female (adjusted
      odds ratio [AOR], 2.28; 95% confidence interval [CI], 1.06-3.50), being in the
      age group of 10-13 years (AOR, 2.94; 95% CI, 1.36-6.22), being in the age group
      of 14-18 years (AOR, 4.06; 95% CI, 2.17-11.95), being a private school student
      (AOR, 2.61; 95% CI, 1.81-4.41), watching television for 2-4 hours/day (AOR, 3.56;
      95% CI, 1.37-7.34), watching television at <1 m (AOR, 7.65; 95% CI, 2.59-34.61),
      watching television at 1-2 m (AOR, 6.89; 95% CI, 1.74-25.27), mobile exposure for
      2-4 hours/day (AOR, 2.61; 95% CI, 1.35-4.58), mobile exposure for >4 hours/day
      (AOR, 3.05; 95% CI, 1.41-9.18), medical visit while experiencing symptoms (AOR,
      11.32; 95% CI, 1.80-82.25) and no medical visit experience (AOR, 3.84; 95% CI,
      0.46-31.76). Conclusion: The majority of the visually impaired school-age
      children had low vision. Sex, age, school type, television exposure duration, the
      distance of television exposure, mobile exposure and medical visit were factors
      associated with visual impairment. Increasing community awareness about early
      detection of visual impairment and providing affordable eye health service may
      decrease the prevalence of visual impairment.

PMID- 29184384
TI  - Treatment of refractory uveitic macular edema: results of a first and second
      implant of long-acting intravitreal dexamethasone.
AB  - Purpose: The purpose of this study was to report the functional and anatomical
      outcomes of a prospective study resulting from repeated dexamethasone
      intravitreal implants in patients with uveitic refractory macular edema. Methods:
      Twelve eyes of 9 patients with intermediate and posterior noninfectious
      inflammatory uveitis complicated with refractory macular edema were regularly
      reviewed after a dexamethasone intravitreal implant. Patients were examined at
      baseline, 30, 90, 135, and 180 days with best-corrected visual acuity (BCVA),
      complete slit-lamp examination, intraocular pressure (IOP), optical coherence
      tomography, and fluorescein angiography. After 6 months of follow-up, eyes were
      reassessed to receive a second implant. Results: BCVA significantly improved when
      comparing the baseline values after the first and second implant (16.2 and 25.8
      letters, respectively, 9.6 letters improvements, p<0.05). BCVA was better after
      the second implant compared to the first one throughout the follow-up, but
      without statistical significance. Mean central macular thickness (CMT) was
      446.3+/-129.9 MUm at baseline and was significantly reduced until day 135
      (p<0.05). CMT reductions after the second injection showed a similar pattern,
      though differences were not statistically significant. Cataract progression was
      observed in 4 of 8 phakic eyes (50%) after the first implant, and in 2 of 3
      phakic eyes following the second implant, with 1 eye requiring cataract surgery.
      One eye developed an IOP >30 mmHg 30 days after the second implant, treated
      topically. Conclusion: Repeated dexamethasone intravitreal implants in uveitic
      patients with refractory macular edema can be used effectively in a clinical
      setting with an acceptable safety profile.

PMID- 29184385
TI  - Aflibercept treatment for neovascular AMD beyond the first year: consensus
      recommendations by a UK expert roundtable panel, 2017 update.
AB  - National recommendations on continued administration of aflibercept solution for
      injection after the first year of treatment for neovascular age-related macular
      degeneration (nAMD) have been developed by an expert panel of UK retina
      specialists, based on clinician experience and treatment outcomes seen in year 2.
      The 2017 update reiterates that the treatment goal is to maintain or improve the
      macular structural and functional gains achieved in year 1 while attempting to
      reduce or minimize the treatment burden, recognizing the need for ongoing
      treatment. At the end of year 1 (ie, the decision visit at month 11), two
      treatment options should be considered: do not extend the treatment interval and
      maintain fixed 8-weekly dosing, or extend the treatment interval using a treat
      and-extend regimen up to a maximum 12 weeks. Criteria for considering not
      extending the treatment interval are persistent macular fluid with stable vision,
      recurrent fluid, decrease in vision in the presence of fluid, macular hemorrhage,
      new choroidal neovascularization or any other sign(s) of exudative disease
      activity considered vision threatening in the opinion of the treating clinician.
      Treatment extension is recommended for eyes with a dry macula (ie, without
      macular fluid) and stable vision. Under both options, the treatment interval may
      be shortened if visual and/or anatomic outcomes deteriorate. Monitoring without
      treatment may be considered for eyes with a fluid-free macula for a minimum
      duration of 48 weeks. A patient completing one full year of monitoring without
      requiring injections may be considered for discharge from clinic. The treatment
      algorithm incorporates return to fixed 8-weekly dosing for disease reactivation
      during treatment extension and reinstatement of treatment for disease recurrence
      following discontinuation or discharge. For bilateral nAMD, either the eye
      requiring the more intensive treatment or the eye with the better vision, guided
      by local clinical practice, should determine the retreatment schedule overall.

PMID- 29184386
TI  - Novel grid combined with peripheral distortion correction for ultra-widefield
      image grading of age-related macular degeneration.
AB  - Purpose: Eyes with age-related macular degeneration (AMD) often harbor
      pathological changes in the retinal periphery and perimacular region. These
      extramacular changes have not been well classified, but may be phenotypically and
      functionally relevant. The purpose of this study was to demonstrate a novel grid
      to systematically study peripheral retinal abnormalities in AMD using geometric
      distortion-corrected ultra-widefield (UWF) imaging. Methods: This is a cross
      sectional observational case series. Consecutive patients with AMD without any
      other coexisting vitreoretinal disease and control patients over age 50 without
      AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured
      200 degrees  UWF images were corrected for peripheral geometric distortion using
      Optos transformation software. A newly developed grid to study perimacular and
      peripheral abnormalities in AMD was then projected onto the images. Results:
      Peripheral and perimacular changes such as drusen, retinal pigment epithelium
      changes and atrophy were found in patients with AMD. The presented grid in
      conjunction with geometric distortion-corrected UWF images allowed for systematic
      study of these peripheral changes in AMD. Conclusion: We present a novel grid to
      study peripheral and posterior pole changes in AMD. The grid is unique in that it
      adds a perimacular zone, which may be important in characterizing certain
      phenotypes in AMD. Our UWF images were corrected for geometric peripheral
      distortion to accurately reflect the anatomical dimensions of the retina. This
      grid offers a reliable and reproducible foundation for the exploration of
      peripheral retinal pathology associated with AMD.

PMID- 29184387
TI  - Lacrimal drainage anomalies in congenital rubella syndrome.
AB  - Purpose: The objective of this study was to ascertain the lacrimal drainage
      anomalies in a cohort of patients suffering from congenital rubella syndrome
      (CRS). Methods: This was a retrospective case series performed in patients with
      CRS presenting with associated lacrimal drainage anomalies (LDA) over 6 years
      from 2011 to 2016. All the patients were confirmed as having CRS after clinical
      and laboratory testing. Data collected include demographics; associated lacrimal,
      ocular, and systemic anomalies; interventions performed for lacrimal anomalies;
      and their anatomical and functional outcomes. Results: Eighty five patients were
      diagnosed as having CRS during the study period, and of these 23 eyes of 12
      patients with associated LDA were included in the study. The prevalence of LDA
      was 14% in CRS. The mean age at presentation was 15.5 weeks, and all except one
      had bilateral presentation. Seventeen eyes were diagnosed with simple congenital
      nasolacrimal duct obstruction (CNLDO) and the remaining six eyes had complex
      CNLDO with buried probes. Additional lacrimal anomalies noted in the six complex
      CNLDO cases included punctal agenesis (n=3), atonic sac (n=3), incomplete punctal
      canalization (n=2), and single canalicular wall hypoplasia (n=1). At a mean
      follow-up of 12.54 months, anatomical and functional success were noted in 91.3%
      (21/23 eyes). Conclusion: Simple CNLDO was the most common of the LDA in CRS.
      Buried probe was universal among the cases with complex CNLDO. All CRS patients
      should be screened for lacrimal anomalies to initiate appropriate interventions
      for successful outcomes.

PMID- 29184388
TI  - Anxiety in patients undergoing cataract surgery: a pre- and postoperative
      comparison.
AB  - Purpose: Reducing surgery-related patient anxiety without under-emphasizing
      surgical risk is challenging for even the most experienced surgeon. The purpose
      of this study is to identify specific anxieties faced by patients in hopes of
      better informing the preoperative surgeon-patient dialogue. Setting:
      Comprehensive and specialty ophthalmology clinics at the University of
      California, San Francisco. Design: A prospective, survey-based study in which a
      pre- and postoperative questionnaire was administered to patients undergoing
      routine phacoemulsification. The surgeon was masked to patient enrollment and
      questionnaire responses. Materials and methods: A 36-item questionnaire on
      patient anxiety was developed from existing literature, building on the validated
      Surgical Fear Questionnaire. Patients were eligible if they were aged >18 years
      and willing to participate. Patients were excluded if having more than
      phacoemulsification alone or if unable to respond in English, and were
      retroactively excluded if there were complications during surgery. The primary
      outcome was self-reported anxiety on an 11-point Likert scale. Results: Sixty-one
      patients were included for analysis. Preoperatively, patients reported greatest
      anxiety around the operation itself and becoming blind. Reflecting
      postoperatively, patients reported the greatest anxiety for the operation itself.
      Statistically significant decreases were greatest for anxiety about the operation
      failing (p<0.001) and becoming blind (p<0.001). No decrease was observed for the
      operation itself (p=0.1). Conclusion: More effort must be made to specifically
      discuss the steps of the operation itself and the expected visual outcomes to
      alleviate patient anxiety. The authors hope these data can provide insight for
      surgeons into patient anxiety surrounding cataract surgery and help strengthen
      the patient-physician relationship.

PMID- 29184390
TI  - Erratum: Quantum mechanics implementation in drug-design workflows: does it
      really help? [Corrigendum].
AB  - [This corrects the article on p. 2551 in vol. 11.].

PMID- 29184389
TI  - Baracle(r) vs Baraclude(r) for 48 weeks in patients with treatment-naive chronic
      hepatitis B: a comparison of efficacy and safety.
AB  - Background and objective: Entecavir (ETV) is a standard of care for chronic
      hepatitis B (CHB). In a bioequivalence study, ETV from Dong-A ST (Baracle(r)) was
      found to have a pharmacokinetic profile equivalent to ETV from Bristol-Myers
      Squibb (BMS) (Baraclude(r)). The present study was conducted to evaluate the
      antiviral activity and safety of ETV from Dong-A ST in comparison to ETV from BMS
      in patients with CHB. Methods: In this multicenter, double-blind, active
      controlled, stratified-randomized, parallel group, comparative trial, 118
      treatment-naive patients with CHB were randomly assigned to receive either 0.5 mg
      of ETV from Dong-A ST or ETV from BMS once daily for 48 weeks. The primary
      efficacy endpoint was virologic improvement (a mean reduction from baseline in
      serum HBV DNA levels) at 24 weeks. Secondary efficacy endpoints included a mean
      reduction in serum HBV DNA levels at 48 weeks, proportion of patients with
      undetectable levels of serum HBV DNA, rates of hepatitis B e antigen (HBeAg) loss
      and seroconversion, rates of HBsAg loss and seroconversion, and rates of
      normalization of alanine aminotransferase (ALT) levels. Results: From baseline to
      week 24, HBV DNA levels (log10) decreased by 4.81 and 4.63 with ETV from Dong-A
      ST and with ETV from BMS, respectively. The upper limit of two-sided 95%
      confidence intervals (CI) (equivalent to one-sided 97.5% CIs) for the difference
      between the treatment groups was 0.208, which was below the noninferiority margin
      of 1, thus supporting the noninferiority of ETV from Dong-A ST in comparison to
      ETV from BMS. No statistically significant differences were noted between the
      treatment groups in all secondary and tertiary efficacy endpoints. Safety
      profiles were also similar between the two groups. Conclusion: In patients with
      previously untreated HBeAg-positive or negative HBV infection, the efficacy of
      ETV from Dong-A ST was noninferior to that of ETV from BMS, and there were no
      significant differences in efficacy or safety between two groups.

PMID- 29184391
TI  - Novel production method of innovative antiangiogenic and antitumor small peptides
      in Escherichia coli.
AB  - Background: Developing innovative drugs with potent efficacy, specificity, and
      high safety remains an ongoing task in antitumor therapy development. In the last
      few years, peptide drugs have become attractive agents in cancer therapy. HM-3,
      mainly with antiangiogenic effect, and AP25, with an additional antiproliferative
      effect, are two peptides designed in our laboratory targeting alphavbeta3 and
      alpha5beta1 integrins, respectively. The low molecular weight of the two peptides
      renders their recombinant expression very difficult, and the complicated
      structure of AP25 makes its chemical synthesis restricted, which presents a big
      challenge for its development. Methods: Bifunctional peptides designed by the
      ligation of HM-3 and AP25, using linkers with different flexibility, were
      prepared using recombinant DNA technology in Escherichia coli. The fusion
      peptides were expressed in a modified auto-induction medium based on a mixture of
      glucose, glycerol, and lactose as carbon substrates and NH4+ as nitrogen source
      without any amino acid or other elements. Subsequently, the antiangiogenic,
      antiproliferative, and cell adhesion assays were conducted to evaluate the
      bioactivity of the two fusion peptides. Results: The peptides were successfully
      expressed in a soluble form without any induction, which allows the culture to
      reach higher cell density before protein expression occurs. Human umbilical vein
      endothelial cell migration assay and chick embryo chorioallantoic membrane assay
      showed, at low doses, a significantly increased antiangiogenic effect (>75%) of
      the purified products compared with the single molecules. Meanwhile, MTT assay
      confirmed their enhanced antitumor activity against gastric cancer cell line MGC
      803; however, no significant effect was observed on hepatoma HepG2 cells and no
      cytotoxicity on normal human lens epithelial cell SRA01/04 and human epithelial
      esophageal cells. Conclusion: Bifunctional molecules with antiangiogenic and
      antiproliferative effects were obtained by using this technique, which presents
      an alternative for small peptide production, instead of the conventional chemical
      method. The increased molecular weight facilitates the peptide expression with a
      simultaneous improvement in their stability and biological activity.

PMID- 29184392
TI  - Paeoniflorin attenuates incipient diabetic nephropathy in streptozotocin-induced
      mice by the suppression of the Toll-like receptor-2 signaling pathway.
AB  - Toll-like receptors (TLRs) may be involved in diabetic nephropathy (DN).
      Paeoniflorin (PF) is an effective Chinese traditional medicine with anti
      inflammatory and immunoregulatory effects that may inhibit the TLR2 signaling
      pathway. In this study, we investigated the effects of PF on the kidneys of mice
      with streptozotocin-induced type 1 diabetes mellitus using TLR2 knockout mice
      (TLR2-/-) and wild-type littermates (C57BL/6J-WT). After 12 weeks of
      intraperitoneal injection of PF at doses of 25, 50, and 100 mg/kg once a day,
      diabetic mice had significantly reduced albuminuria and attenuated renal
      histopathology. These changes were associated with substantially alleviated
      macrophage infiltration and decreased expression of TLR2 signaling pathway
      biomarkers. These data support a role of TLR2 in promoting inflammation and
      indicate that the effect of PF is associated with the inhibition of the TLR2
      pathway in the kidneys of diabetic mice. PF thus shows therapeutic potential for
      the prevention and treatment of DN.

PMID- 29184393
TI  - Recovery in patients with major depressive disorder (MDD): results of a 6-month,
      multinational, observational study.
AB  - Not all individuals treated for major depressive disorder (MDD) achieve recovery.
      This observational study examined the recovery rates in MDD patients and the
      patient characteristics associated with achieving recovery in a naturalistic
      clinical setting. Recovery was defined as having both clinical and functional
      remission. Data for this post hoc analysis were taken from a 24-week prospective,
      observational study that involved 1,549 MDD patients. Clinical remission was
      assessed using the 16-item Quick Inventory of Depressive Symptomatology Self
      Report and functional remission through the Sheehan Disability Scale and no days
      of reduced productivity in the previous week. Generalized estimating equation
      regression models were used to examine the baseline factors associated with
      recovery during follow-up. Clinical and functional remission was achieved in
      70.6% and 56.1% of the MDD patients, respectively. MDD patients who achieved
      recovery (52.1%) were significantly less likely to have impaired levels of
      functioning, concurrent medical or psychiatric conditions, low levels of
      education, or nonadherence to therapy at follow-up. The level of functioning
      during the index episode seems to be a better predictor of recovery than symptom
      severity. Therefore, the level of functioning should be considered while
      determining recovery from depression.

PMID- 29184394
TI  - Highly specific reasons for nonadherence to antiretroviral therapy: results from
      the German adherence study.
AB  - Background: Reasons for and frequency of nonadherence to antiretroviral therapy
      (ART) may have changed due to pharmacological improvements. In addition, the
      importance of known non-pharmacologic reasons for nonadherence is unclear.
      Methods: We performed a cross-sectional, noninterventional, multicenter study to
      identify current reasons for nonadherence. Patients were categorized by
      physicians into the following adherence groups: good, unstable, or poor
      adherence. Co-variables of interest included age, sex, time since HIV diagnosis,
      ART duration, current ART regimen, HIV transmission route, comorbidity, HIV-1 RNA
      viral load (VL), and CD4 cell count. Patients self-reported the number of missed
      doses and provided their specific reasons for nonadherent behavior. Statistical
      analyses were performed using Fisher's extended exact test, Kruskal-Wallis test,
      and logistic regression models. Results: Our study assessed 215 participants with
      good (n=162), unstable (n=36), and poor adherence (n=17). Compared to patients
      with good adherence, patients with unstable and poor adherence reported more
      often to have missed at least one dose during the last week (good 11% vs unstable
      47% vs poor 63%, p<0.001). Physicians' adherence assessment was concordant with
      patients' self-reports of missed doses during the last week (no vs one or more)
      in 81% cases. Similarly, we found a strong association of physicians' assessment
      with viral suppression. Logistic regression analysis showed that "reduced
      adherence" - defined as unstable or poor - was significantly associated with
      patients <30 years old, intravenous drug use, history of acquired immune
      deficiency syndrome (AIDS), and psychiatric disorders (p<0.05). Univariate
      analyses showed that specific reasons, such as questioning the efficacy/dosing of
      ART, HIV stigma, interactive toxicity beliefs regarding alcohol and/or party
      drugs, and dissatisfaction with regimen complexity, correlated with unstable or
      poor adherence (p<0.05). Conclusion: Identification of factors associated with
      poor adherence helps in identifying patients with a higher risk for nonadherence.
      Reasons for nonadherence should be directly addressed in every patient, because
      they are common and constitute possible adherence intervention points.

PMID- 29184396
TI  - Excessive anterior cervical muscle tone affects hyoid bone kinetics during
      swallowing in adults.
AB  - Purpose: This study aimed to determine whether excessive neck muscle tone affects
      hyoid bone kinetics during swallowing using videofluorography (VF) in an
      unnatural posture in adults. Subjects and methods: Subjects were 28 adults (12
      men, 16 women; mean age, 39.75+/-9.50 years) who were suspected to have some
      symptom of swallowing disorders but did not have swallowing dysfunctional from
      the result of videofluorography. We first established the participant's posture a
      reclining wheelchair that was adjusted to a 30-degree angle with the headrest
      (without excessive neck muscle tone) or without headrest (with excessive neck
      muscle tone), used an electromyogram above the mylohyoid muscle to represent the
      suprahyoid muscles and above the sternohyoid muscle to represent the infrahyoid
      muscles to confirm neck muscle tone, and then conducted VF of swallowing
      measurements. Videofluorographic images were obtained when 5 mL of 50% (w/v)
      barium sulfate was being swallowed, and hyoid bone coordinate (the resting
      position and the elevated position), extent of horizontal and vertical hyoid bone
      elevation, as well as duration and velocity of hyoid bone elevation were
      evaluated (x-axis and y-axis coordinates for the resting position of hyoid bone
      are referred to as Xr and Yr, respectively; those for the elevated hyoid bone
      position induced during swallowing are referred to as Xs and Ys, respectively).
      Results: In the resting position of the hyoid bone, the Yr coordinates in those
      with excessive neck muscle tone were significantly lower than in those without
      excessive neck muscle tone. Vertical hyoid bone elevation and hyoid bone
      elevation velocity were significantly higher with excessive neck muscle tone than
      without excessive neck muscle tone, whereas horizontal elevation showed no
      significant differences. Conclusion: Our findings suggest that the generation of
      neck muscle tone due to inappropriate posture may encourage hyoid depression and
      increase the extent of hyoid bone elevation, thereby increasing the risk of
      aspiration.

PMID- 29184397
TI  - Do older drivers with bilateral cataract self-regulate their driving while
      waiting for first eye cataract surgery?
AB  - Objectives: To analyze the association between visual impairment and driver self
      regulation among a cohort of older drivers waiting for first eye cataract
      surgery. Methods: Ninety-six drivers with bilateral cataract aged 55+ years were
      assessed before first eye cataract surgery. Data collection consisted of a
      researcher-administered questionnaire, objective visual measures (visual acuity,
      contrast sensitivity and stereopsis), a visual attention test (the useful field
      of view test) and a cognitive test (the Mini-Mental State Examination). Driver
      self-regulation practices were collected using the Driving Habits Questionnaire
      and were also measured with an in-vehicle monitoring device. Characteristics of
      self-regulators and non-self-regulators were compared and a logistic regression
      model was used to examine the association between 3 objective visual measures and
      driver self-regulation status. Results: After controlling for potential
      confounding factors, only binocular contrast sensitivity (p=0.01), age (p=0.03)
      and gender (p=0.03) were significantly associated with driver self-regulation
      status. The odds of participants with better contrast sensitivity scores (better
      vision) self-regulating their driving in at least 1 driving situation decreased
      (odds ratio [OR]: 0.01, 95% CI: 0.00-0.28) while those of increasing age reported
      an increased odds of self-regulating their driving (OR: 1.08, 95% CI: 1.01-1.15).
      The odds of males self-regulating their driving was decreased compared with
      females (OR: 0.28, 95% CI: 0.09-0.86). Conclusions: Worse binocular contrast
      sensitivity scores, increasing age and being female were significantly associated
      with driver self-regulation. The study highlighted that while self-regulation was
      common among cataract patients, a proportion of those with poor vision did not
      self-regulate. Further research should determine how cataract patients could
      benefit from self-regulation strategies while waiting for cataract surgery.

PMID- 29184395
TI  - Does eating less make you live longer and better? An update on calorie
      restriction.
AB  - The complexity of aging is hard to be captured. However, apart from its tissue
      specific features, a structural and functional progressive decline of the whole
      organism that leads to death, often preceded by a phase of chronic morbidity,
      characterizes the common process of aging. Therefore, the research goal of
      scientists in the field moved from the search for strategies able to extend
      longevity to those ensuring healthy aging associated with a longer lifespan
      referred to as "healthspan". The aging process is plastic and can be tuned by
      multiple mechanisms including dietary and genetic interventions. To date, the
      most robust approach, efficient in warding off the cellular markers of aging, is
      calorie restriction (CR). Here, after a preliminary presentation of the major
      debate originated by CR, we concisely overviewed the recent results of CR
      treatment on humans. We also provided an update on the molecular mechanisms
      involved by CR and the effects on some of the age-associated cellular markers. We
      finally reviewed a number of tested CR mimetics and concluded with an evaluation
      of future applications of such dietary approach.

PMID- 29184398
TI  - The role of pain in pulmonary rehabilitation: a qualitative study.
AB  - Introduction: One third of individuals with chronic obstructive pulmonary disease
      (COPD) report pain. To help inform a COPD-specific pain intervention, we explored
      the views of health care providers (HCPs) and individuals with COPD on pain
      during pulmonary rehabilitation (PR). Methods: This is a qualitative study using
      inductive thematic analysis. Eighteen HCPs familiar with PR and 19 patients
      enrolled in PR participated in semi-structured interviews. Demographic data were
      recorded, and the patients completed the Brief Pain Inventory (Short Form).
      Results: 1) Interaction between pain and COPD: pain is a common experience in
      COPD, heightened by breathlessness and anxiety. 2) Pain interfering with PR: a)
      Communicating pain: HCPs rarely ask about pain and patients are reluctant to
      report it for fear of being removed from PR. b) PR is a short-term aggravator but
      long-term reliever: although pain limits exercise, concentration, and program
      adherence, PR may reduce pain by increasing muscle strength and improving coping.
      c) Advice and strategies for pain: some attention is given to pain management but
      this is often counterproductive, encouraging patients to cease exercise. 3) An
      intervention to manage pain: HCPs were enthusiastic about delivering a pain
      intervention within their knowledge and time constraints. Early group education
      was preferred. Conclusion: A pain intervention seems warranted in PR and may
      improve adherence and therefore clinical benefit. A pain intervention could be
      provided as part of PR education with HCP training.

PMID- 29184399
TI  - Application of a lipid-coated hollow calcium phosphate nanoparticle in
      synergistic co-delivery of doxorubicin and paclitaxel for the treatment of human
      lung cancer A549 cells.
AB  - In this study, we developed a lipid-coated hollow calcium phosphate (LCP)
      nanoparticle for the combined application of two chemotherapeutic drugs to human
      lung cancer A549 cells. Hydrophilic doxorubicin (DOX) was incorporated into the
      hollow structure of hollow calcium phosphate (HCP), and a lipid bilayer
      containing hydrophobic paclitaxel (PTX) was subsequently coated on the surface of
      HCP. The study on combinational effects demonstrated that the combination of DOX
      and PTX at a mass ratio of 12:1 showed a synergistic effect against A549 cells.
      The particle size, zeta potential, and encapsulation efficiency were measured to
      obtain optimal values: particle size was 335.0 3.2 nm, zeta potential -41.1 mV,
      and encapsulation efficiency 80.40%+/-2.24%. An in vitro release study indicated
      that LCP produced a sustained drug release. A549 cells had a better uptake of LCP
      with good biocompatibility. Furthermore, in vitro cytotoxicity experiment,
      apoptosis analysis, in vivo anti-tumor efficacy and protein expression analysis
      of Bax, Bcl-2, and Caspase-3 demonstrated that the co-delivery system based on
      LCP had significant synergistic anti-tumor activity. All conclusions suggested
      that LCP is a promising platform for co-delivery of multiple anti-tumor drugs.

PMID- 29184400
TI  - Drug delivery to solid tumors: the predictive value of the multicellular tumor
      spheroid model for nanomedicine screening.
AB  - The increasing number of publications on the subject shows that nanomedicine is
      an attractive field for investigations aiming to considerably improve anticancer
      chemotherapy. Based on selective tumor targeting while sparing healthy tissue,
      carrier-mediated drug delivery has been expected to provide significant benefits
      to patients. However, despite reduced systemic toxicity, most nanodrugs approved
      for clinical use have been less effective than previously anticipated. The gap
      between experimental results and clinical outcomes demonstrates the necessity to
      perform comprehensive drug screening by using powerful preclinical models. In
      this context, in vitro three-dimensional models can provide key information on
      drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS)
      model closely mimics a small avascular tumor with the presence of proliferative
      cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient
      gradients are similar to those of solid tumor. Furthermore, extracellular matrix
      (ECM) components and stromal cells can be embedded in the most sophisticated
      spheroid design. All these elements together with the physicochemical properties
      of nanoparticles (NPs) play a key role in drug transport, and therefore, the MCTS
      model is appropriate to assess the ability of NP to penetrate the tumor tissue.
      This review presents recent developments in MCTS models for a better
      comprehension of the interactions between NPs and tumor components that affect
      tumor drug delivery. MCTS is particularly suitable for the high-throughput
      screening of new nanodrugs.

PMID- 29184401
TI  - Placenta-derived exosomes: potential biomarkers of preeclampsia.
AB  - Preeclampsia remains a leading cause of maternal and fetal mortality, due to
      ineffective treatment and diagnostic strategies, compounded by the lack of
      clarity on the etiology of the disorder. Although several clinical and biological
      markers of preeclampsia have been evaluated, they have proven to be ineffective
      in providing a definitive diagnosis during the various stages of the disorder.
      Exosomes have emerged as ideal biomarkers of pathological states, such as cancer,
      and have more recently gained interest in pregnancy-related complications, due to
      their role in cellular communication in normal and complicated pregnancies. This
      occurs as a result of the specific placenta-derived exosomal molecular cargo,
      which may be involved in normal pregnancy-associated immunological events, such
      as the maintenance of maternal-fetal tolerance. This review provides perspectives
      on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis
      of preeclampsia. Using keywords, online databases were searched to identify
      relevant publications to review the potential use of placenta-derived exosomes as
      biomarkers of preeclampsia.

PMID- 29184402
TI  - Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic
      therapy of T cell acute lymphoblastic leukemia.
AB  - T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of
      variant T cell progenitors and is considered as a high risk leukemia.
      Contemporary single chemotherapy has a limited effect due to dynamic and
      versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co
      encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid)
      nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The
      formulation was optimized to achieve high drug loading using Box-Behnken design
      and response surface methodology. The optimal parameter comprised 2.98% polymer
      in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12%
      emulsifier concentration. High drug loading and uniform spherical shape was
      achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor
      for 72 hours as well as sustained release of ABT-737 for more than 120 hours.
      Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT
      NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC50 of
      IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells.
      Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited
      greater cytotoxicity toward T-ALL cells, the capacity to significantly restore
      white blood cell number in peripheral blood, and improved survival time of T-ALL
      mouse model compared to the IRAK1/4 and ABT-737 combined solution.

PMID- 29184403
TI  - Confocal laser scanning microscopy to estimate nanoparticles' human skin
      penetration in vitro.
AB  - Objective: With rapid development of nanotechnology, there is increasing interest
      in nanoparticle (NP) application and its safety and efficacy on human skin. In
      this study, we utilized confocal laser scanning microscopy to estimate NP skin
      penetration. Methods: Three different-sized polystyrene NPs marked with red
      fluorescence were applied to human skin, and Calcium Green 5N was used as a
      counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative
      vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model.
      Skin biopsies dosed with NPs were incubated at 4 degrees C or 37 degrees C for 24
      hours and imaged using confocal laser scanning microscopy. Results: NPs were
      localized in the stratum corneum (SC) and hair follicles without penetrating the
      epidermis/dermis. Barrier alteration with tape stripping and change in incubation
      temperature did not induce deeper penetration. DMSO enhanced NP SC penetration
      but ethanol did not. Conclusion: Except with DMSO vehicle, these hydrolyzed
      polystyrene NPs did not penetrate intact or barrier-damaged human "viable"
      epidermis. For further clinical relevance, in vivo human skin studies and more
      sensitive analytic chemical methodology are suggested.

PMID- 29184404
TI  - Autophagic flux induced by graphene oxide has a neuroprotective effect against
      human prion protein fragments.
AB  - Graphene oxide (GO) is a nanomaterial with newly developing biological
      applications. Autophagy is an intracellular degradation system that has been
      associated with the progression of neurodegenerative disorders. Although
      induction of autophagic flux by GO has been reported, the underlying signaling
      pathway in neurodegenerative disorders and how this is involved in
      neuroprotection remain obscure. We show that GO itself activates autophagic flux
      in neuronal cells and confers a neuroprotective effect against prion protein
      (PrP) (106-126)-mediated neurotoxicity. GO can be detected in SK-N-SH neuronal
      cells, where it triggers autophagic flux signaling. GO-induced autophagic flux
      prevented PrP (106-126)-induced neurotoxicity in SK-N-SH cells. Moreover,
      inactivation of autophagic flux blocked GO-induced neuroprotection against prion
      mediated mitochondrial neurotoxicity. This is the first study to demonstrate that
      GO regulates autophagic flux in neuronal cells, and that activation of autophagic
      flux signals, induced by GO, plays a neuroprotective role against prion-mediated
      mitochondrial neurotoxicity. These results suggest that the nanomaterial GO may
      be used to activate autophagic flux and could be used in neuroprotective
      strategies for treatment of neurodegenerative disorders, including prion
      diseases.

PMID- 29184405
TI  - Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules
      in rats.
AB  - Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery
      since they can be nebulized without any structural or functional changes, and the
      aerosols produced are highly compatible with pulmonary drug delivery in human
      beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and
      pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel
      loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained
      unchanged. Biodistribution study showed a homogeneous repartition in the lungs in
      rats with an improvement in lung retention of the radiolabeled tracer loaded in
      LNCs compared to the absence of LNCs with a lung half-time of 8.8+/-0.7 hours.
      Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation,
      reaching a maximum between days 2 and 4, characterized by a peak of granulocytes
      at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were
      increased at days 3 and 7. Acute inflammation was increased with paclitaxel
      loaded LNCs in comparison with blank LNCs but dropped out at day 7. No
      histological pulmonary lesion was observed at day 60. LNCs lowered surface
      tension to a greater degree than Curosurf(r) in a physicochemical model of the
      pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term
      alveolar inflammation with no residual lesions in rats at day 60. These data
      permit to start the study of LNCs in surfactant replacement therapy.

PMID- 29184406
TI  - Effect of A-317491 delivered by glycolipid-like polymer micelles on endometriosis
      pain.
AB  - Endometriosis is a common gynecological disease with a lack of effective clinical
      treatment. Current therapy often results in endometriosis pain recurrence and
      serious side effects. P2X3 receptor, an adenosine triphosphate (ATP)-gated ion
      channel, might be implicated in endometriosis pain. In this study, chitosan
      oligosaccharide-g-stearic acid (CSOSA) polymer micelles-coated nanostructured
      lipid carriers (NLCs) were developed as a novel delivery system for A-317491, a
      selective P2X3 receptor antagonist for endometriosis pain therapy. A-317491
      loaded NLC (NLC/A-317491) could be coated by CSOSA micelles to form CSOSA/NLC/A
      317491 nanoparticles. Pheochromocytoma PC12 cells, which highly expressed P2X3
      receptors, were used as a cell model, and the CSOSA/NLC/A-317491 partly blocked
      the Ca2+ influx induced by ATP stimulation. In nude mouse and rat endometriotic
      models, CSOSA/NLC could accumulate into endometriotic lesions after vein
      injection. In endometriotic rats, CSOSA/NLC/A-317491 reversed mechanical and heat
      hyperalgesia with long-term efficacy, which might be attributed to the massive
      CSOSA/NLC/A-317491 distribution in the endometriotic lesions. In conclusion, A
      317491 delivered by CSOSA/NLC nanoparticles attenuated endometriosis pain in
      rats, and CSOSA/NLC/A-317491 could be used as an effective treatment strategy for
      P2X3-targeted therapy in endometriosis pain.

PMID- 29184407
TI  - Photodynamic therapy by conjugation of cell-penetrating peptide with
      fluorochrome.
AB  - Photodynamic therapy (PDT) is a promising alternative therapy that could be used
      as an adjunct to chemotherapy and surgery for cancer, and works by destroying
      tissue with visible light in the presence of a photosensitizer (PS) and oxygen.
      The PS should restrict tissue destruction only to the tumor and be activated by
      light of a specific wavelength; both of these properties are required. Arginine
      rich peptides, such as cell-penetrating peptides, have membrane-translocating and
      nuclear-localizing activities, which have led to their application in various
      drug delivery modalities. Protamine (Pro) is an arginine-rich peptide with
      membrane-translocating and nuclear-localizing properties. The reaction of an N
      hydroxysuccinimide (NHS) ester of rhodamine (Rho) and clinical Pro was carried
      out in this study to yield RhoPro, and a demonstration of its phototoxicity,
      wherein clinical Pro improved the effect of PDT, was performed. The reaction
      between Pro and the NHS ester of Rho is a solution-phase reaction that results in
      the complete modification of the Pro peptides, which feature a single reactive
      amine at the N-terminal proline and a single carboxyl group at the C-terminal
      arginine. This study aimed to identify a new type of PS for PDT by in vitro and
      in vivo experiments and to assess the antitumor effects of PDT, using the Pro
      conjugated PS, on a cancer cell line. Photodynamic cell death studies showed that
      the RhoPro produced has more efficient photodynamic activities than Rho alone,
      causing rapid light-induced cell death. The attachment of clinical Pro to Rho,
      yielding RhoPro, confers the membrane-internalizing activity of its arginine-rich
      content on the fluorochrome Rho and can induce rapid photodynamic cell death,
      presumably owing to light-induced cell membrane rupture. PDT using RhoPro for HT
      29 cells was very effective and these findings suggest that RhoPro is a suitable
      candidate as a PS for solid tumors.

PMID- 29184408
TI  - Size-controlled fabrication of zein nano/microparticles by modified anti-solvent
      precipitation with/without sodium caseinate.
AB  - Zein-based nano/microparticles have been demonstrated to be promising carrier
      systems for both the food industry and biomedical applications. However, the
      fabrication of size-controlled zein particles has been a challenging issue. In
      this study, a modified anti-solvent precipitation method was developed, and the
      effects of various factors, such as mixing method, solvent/anti-solvent ratio,
      temperature, zein concentrations and the presence of sodium caseinate (SC) on
      properties of zein particles were investigated. Evidence is presented that, among
      the previously mentioned factors, the mixing method, especially mixing rate,
      could be used as an effective parameter to control the size of zein particles
      without changing other parameters. Moreover, through fine-tuning the mixing rate
      together with zein concentration, particles with sizes ranging from nanometers to
      micrometers and low polydispersity index values could be easily obtained. Based
      on the size-controlled fabrication method, SC-coated zein nanoparticles could
      also be obtained in a size-controlled manner by incubation of the coating
      material with the already-formed zein particles. The resultant nanoparticles
      showed better performance in both drug loading and controlled release, compared
      with zein/SC hybrid nanoparticles fabricated by adding aqueous ethanol solution
      to SC solution. The possible mechanisms of the nanoprecipitation process and self
      assembly formation of these nanoparticles are discussed.

PMID- 29184409
TI  - Nanomaterials for alternative antibacterial therapy.
AB  - Despite an array of cogent antibiotics, bacterial infections, notably those
      produced by nosocomial pathogens, still remain a leading factor of morbidity and
      mortality around the globe. They target the severely ill, hospitalized and
      immunocompromised patients with incapacitated immune system, who are prone to
      infections. The choice of antimicrobial therapy is largely empirical and not
      devoid of toxicity, hypersensitivity, teratogenicity and/or mutagenicity. The
      emergence of multidrug-resistant bacteria further intensifies the clinical
      predicament as it directly impacts public health due to diminished potency of
      current antibiotics. In addition, there is an escalating concern with respect to
      biofilm-associated infections that are refractory to the presently available
      antimicrobial armory, leaving almost no therapeutic option. Hence, there is a
      dire need to develop alternate antibacterial agents. The past decade has
      witnessed a substantial upsurge in the global use of nanomedicines as innovative
      tools for combating the high rates of antimicrobial resistance. Antibacterial
      activity of metal and metal oxide nanoparticles (NPs) has been extensively
      reported. The microbes are eliminated either by microbicidal effects of the NPs,
      such as release of free metal ions culminating in cell membrane damage, DNA
      interactions or free radical generation, or by microbiostatic effects coupled
      with killing potentiated by the host's immune system. This review encompasses the
      magnitude of multidrug resistance in nosocomial infections, bacterial evasion of
      the host immune system, mechanisms used by bacteria to develop drug resistance
      and the use of nanomaterials based on metals to overcome these challenges. The
      diverse annihilative effects of conventional and biogenic metal NPs for
      antibacterial activity are also discussed. The use of polymer-based nanomaterials
      and nanocomposites, alone or functionalized with ligands, antibodies or
      antibiotics, as alternative antimicrobial agents for treating severe bacterial
      infections is also discussed. Combinatorial therapy with metallic NPs, as adjunct
      to the existing antibiotics, may aid to restrain the mounting menace of bacterial
      resistance and nosocomial threat.

PMID- 29184411
TI  - Depression, anxiety, stress, and their associated factors among Jimma University
      staff, Jimma, Southwest Ethiopia, 2016: a cross-sectional study.
AB  - Background: Worldwide, approximately 450 million people suffer from mental
      disorders. Of these, approximately 150 million are affected with depression.
      Depression, anxiety, and stress have an impact on productivity, motivation to
      work, sleep behavior of the individual, and outcome of different chronic
      diseases. However, till date, there are no studies which evaluated mental health
      problems among university staff in Ethiopia. Therefore, in this study, we aimed
      to assess the prevalence of depression, anxiety, stress, and their associated
      factors among Jimma University staff. Methods: An institution-based cross
      sectional study was conducted among 354 staff of Jimma University from March 24
      to April 24, 2016. Stratified simple random sampling technique was used.
      Pretested interviewer-administered Depression, Anxiety and Stress Scale (DASS-21)
      questionnaire was used to collect the data. Data were analyzed using SPSS Version
      20.0 software. Results: The prevalence of depression, anxiety, and stress in this
      study was found to be approximately 22.9%, 19.2%, and 28.2%, respectively. Being
      female (adjusted odds ratio [AOR] =2.43, 95% confidence interval [CI] =1.22
      4.77), no job satisfaction (AOR =10.59, 95% CI =4.88-22.98), presence of conflict
      with colleagues (AOR =2.33, 95% CI =1.21-4.49), and khat chewing (AOR =4.99, 95%
      CI =2.57-9.69) were associated with depression. Presence of conflict with
      colleagues (AOR =2.46, 95% CI =1.25-4.85), no job satisfaction (AOR =7.12, 95% CI
      =3.29-15.45), and khat chewing (AOR =2.94, 95% CI =1.52-5.66) were associated
      with anxiety. Being widowed (AOR =7.46, 95% CI =1.11-50.15), female (AOR =2.72,
      95% CI =1.40-5.28), no job satisfaction (AOR =6.69, 95% CI =3.46-12.97), khat
      chewing (AOR =2.78, 95% CI =1.49-5.21), and presence of conflict with colleagues
      (AOR =2.93, 95% CI =1.57-5.46) were associated with stress. Conclusion: The
      burden of depression, anxiety, and stress among Jimma University staff was found
      to be high. Being female, widowed, or khat chewer or having a history of conflict
      with colleagues and no job satisfaction were predictors of depression, anxiety,
      and stress. Therefore, it is recommended to design preventive strategies to
      reduce the risk of these problems and to minimize the disease burden.

PMID- 29184410
TI  - Anti-MRSA malleable liposomes carrying chloramphenicol for ameliorating hair
      follicle targeting.
AB  - Pathogens usually invade hair follicles when skin infection occurs. The
      accumulated bacteria in follicles are difficult to eradicate. The present study
      aimed to assess the cutaneous and follicular delivery of chloramphenicol (Cm)
      loaded liposomes and the antibacterial activity of these liposomes against
      methicillin-resistant Staphylococcus aureus (MRSA). Skin permeation was conducted
      by in vitro Franz diffusion cell. The anti-MRSA potential was checked using
      minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC),
      a well diffusion test, and intracellular MRSA killing. The classic,
      dimyristoylphosphatidylcholine (DMPC), and deoxycholic acid (DA) liposomes had a
      vesicle size of 98, 132, and 239 nm, respectively. The incorporation of DMPC or
      DA into the liposomes increased the bilayer fluidity. The malleable vesicles
      containing DMPC and DA showed increased follicular Cm uptake over the control
      solution by 1.5- and 2-fold, respectively. The MIC and MBC of DA liposomes loaded
      with Cm were 62.5 and 62.5-125 MUg/mL, comparable to free Cm. An inhibition zone
      about 2-fold higher was achieved by DA liposomes as compared to the free control
      at a Cm dose of 0.5 mg/mL. DA liposomes also augmented antibacterial activity on
      keratinocyte-infected MRSA. The deformable liposomes had good biocompatibility
      against keratinocytes and neutrophils (viability >80%). In vivo administration
      demonstrated that DA liposomes caused negligible toxicity on the skin, based on
      physiological examination and histology. These data suggest the potential
      application of malleable liposomes for follicular targeting and the treatment of
      MRSA-infected dermatologic conditions.

PMID- 29184412
TI  - A 6-year study of complicated urinary tract infections in southern China:
      prevalence, antibiotic resistance, clinical and economic outcomes.
AB  - Urinary tract infections (UTIs) are common nosocomial infections. This study
      evaluated the prevalence, pathogens, antibiotic resistances, clinical outcomes,
      and hospitalization costs associated with complicated UTIs in southern China, and
      risk factors delaying patient discharge. We retrospectively reviewed electronic
      medical records of 4,284 (61.4% women) complicated UTI-related hospitalizations
      from 2008 to 2013. Average patient age was 61.1 years and median hospital stay
      was 11 days. Pathogens were isolated from 1,071 urine and 148 blood specimens.
      Gram-negative bacteria were the most frequent and included Escherichia coli
      (48.2%), Klebsiella pneumoniae (9.5%), Pseudomonas aeruginosa (4.9%), and Proteus
      mirabilis (4.6%), while Enterococcus spp. (14.4%) was the most common Gram
      positive bacteria causing UTIs. Both E. coli and K. pneumoniae showed high
      resistance rates (>45%) to wide-spectrum penicillins, cephalosporins, aztreonam,
      and ciprofloxacin. Resistances to beta-lactamase inhibitor/beta-lactam antibiotic
      combination were relatively lower. Imipenem, meropenem, and amikacin had the
      greatest activity against E.coli and K. pneumoniae. Recurrent infection was a
      risk factor for mortality. Age, sex, previous surgery, diabetes, and renal
      insufficiency were significant risk factors for delayed discharge (P<0.01).
      Response to initial treatment was associated with a lower cost. Initial empiric
      use of antibiotics least associated with resistance may reduce costs and medical
      resource usage.

PMID- 29184413
TI  - Near-fatal asthma responsive to mepolizumab after failure of omalizumab and
      bronchial thermoplasty.
AB  - Severe asthma affects between 5% and 10% of patients with asthma worldwide and
      requires best standard therapies at maximal doses, but there is a subgroup of
      patients refractory to all treatments. We share a case report of a 53-year-old
      woman with a history of severe allergic asthma that progressively worsened over
      the years despite the best therapy. She had been hospitalized 35 times, including
      nine admissions to the respiratory intensive care unit due to severe
      exacerbations. To rule out other possible diagnoses, several investigations were
      performed, such as computed tomography scan of the chest and neck, fiberoptic
      laryngoscopy, antineutrophil cytoplasmic antibodies, and complete blood cell
      count. The patient was first treated with omalizumab, which was completely
      ineffective, and then with bronchial thermoplasty (BT), again without clinical
      benefit. The situation remained critical for about 3 months during the last
      hospitalization, but in February 2017, the Italian Medicines Agency approved the
      treatment of severe refractory eosinophilic asthma with mepolizumab (Nucala(r)).
      Given a blood eosinophil count of 300 cells/MUL, our patient was started on 100
      mg mepolizumab treatment. After the second administration, symptoms improved
      progressively, with a reduction in the number and severity of exacerbations, so
      the patient could finally be discharged from hospital. At follow-up, it was
      possible to reduce and then suspend oral corticosteroids by continuing only with
      inhaled corticosteroids/long-acting beta-agonists and montelukast. No further
      asthmatic exacerbations occurred; symptom control and quality of life improved
      significantly. To our knowledge, this is the first case of a patient unresponsive
      to omalizumab and BT but with excellent clinical response to mepolizumab. She is
      also the first patient to be treated with an anti-IL5 agent in Italy in a real
      life clinical setting. The availability of new effective biological agents will
      allow many patients to resume as normal a life as possible, with a positive
      outcome also from a social and economic point of view.

PMID- 29184414
TI  - Omentum flap as a salvage procedure in deep sternal wound infection.

PMID- 29184415
TI  - Reversible preoperative renal dysfunction does not add to the risk of
      postoperative acute kidney injury after cardiac valve surgery.
AB  - Objective: To evaluate the impact of the renal dysfunction (RD) type and change
      of postoperative cardiac function on the risk of developing acute kidney injury
      (AKI) in patients who underwent cardiac valve surgery. Method: Reversible renal
      dysfunction (RRD) was defined as preoperative RD in patients who had not been
      initially diagnosed with chronic kidney disease (CKD). Cardiac function
      improvement (CFI) was defined as postoperative left ventricular ejection function
      - preoperative left ventricular ejection function (DeltaEF) >0%, and cardiac
      function not improved (CFNI) as DeltaEF <=0%. Results: Of the 4,805 (94%) cardiac
      valve surgery patients, 301 (6%) were RD cases. The AKI incidence in the RRD
      group (n=252) was significantly lower than in the CKD group (n=49) (36.5% vs
      63.3%, P=0.018). The AKI and renal replacement therapy incidences in the CFI
      group (n=174) were significantly lower than in the CFNI group (n=127) (33.9% vs
      50.4%, P=0.004; 6.3% vs 13.4%, P=0.037). After adjustment for age, gender, and
      other confounding factors, CKD and CKD + CFNI were identified as independent risk
      factors for AKI in all patients after cardiac valve surgery. Multivariate
      logistic regression analysis showed that the risk factors for postoperative AKI
      in preoperative RD patients were age, gender (male), hypertension, diabetes,
      chronic heart failure, cardiopulmonary bypass time (every 1 min added), and
      intraoperative hypotension, while CFI after surgery could reduce the risk.
      Conclusion: For cardiac valve surgery patients, preoperative CKD was an
      independent risk factor for postoperative AKI, but RRD did not add to the risk.
      Improved postoperative cardiac function can significantly reduce the risk of
      postoperative AKI.

PMID- 29184417
TI  - Primary site surgery for metastatic adrenocortical carcinoma improves survival
      outcomes: an analysis of a population-based database.
AB  - Objective: To define the survival effect of surgery of primary adrenal malignant
      lesions in metastatic adrenocortical carcinoma (ACC) patients. Patients and
      methods: We used the Surveillance, Epidemiology and End Results (SEER) database
      (1973-2014) to identify metastatic ACC patients (stage IV by using European
      Network for the Study of Adrenal Tumors stage classification). Correlated
      variables, including age, sex, race, tumor laterality, treatment modality, lymph
      node dissection, surgery of metastatic site, tumor size, and tumor stage, were
      extracted. Univariate and multivariate Cox regression analyses were used to
      define the efficacy of surgery on survival outcomes, including overall survival
      and cancer-specific survival of ACC. Results: There were 290 metastatic ACC
      patients identified from the database. The overall median survival time was 7
      (95% CI, 6-8) months. Among these patients, 118 patients received primary site
      surgery and 172 patients did not. In both univariate and multivariate analyses,
      primary site surgery significantly improved both overall (hazard ratio 0.413, 95%
      CI, 0.299-0.571, P<0.01) and cancer-specific survival (hazard ratio 0.408, 95%
      CI, 0.290-0.574, P<0.01) for metastatic ACC patients. Conclusion: Our study
      suggests that primary site surgery in metastatic ACC patients significantly
      improved overall and cancer-specific survival. Further multicenter prospective
      studies are still needed to validate these outcomes.

PMID- 29184416
TI  - Variations in patient safety climate and perceived quality of collaboration
      between professions in out-of-hours care.
AB  - Purpose: To get an overview of health care workers perceptions of patient safety
      climates and the quality of collaboration in Slovenian out-of-hours health care
      (OOHC) between professional groups. Materials and methods: This was a cross
      sectional study carried out in all (60) Slovenian OOHC clinics; 37 (61.7%) agreed
      to participate with 438 employees. The questionnaire consisted of the Slovenian
      version of the Safety Attitudes Questionnaire - Ambulatory Version (SAQ-AV).
      Results: The study sample consisted of 175 (70.0%) physicians, nurse
      practitioners, and practice nurses. Practice nurses reported the highest patient
      safety climate scores in all dimensions. Total mean (standard deviation) SAQ-AV
      score was 60.9+/-15.2. Scores for quality of collaboration between different
      professional groups were high. The highest mean scores were reported by nurse
      practitioners on collaboration with practice nurses (4.4+/-0.6). The lowest mean
      scores were reported by practice nurses on collaboration with nurse practitioners
      (3.8+/-0.9). Conclusion: Due to large variations in Slovenian OOHC clinics with
      regard to how health care workers from different professional backgrounds
      perceive safety culture, more attention should be devoted to improving the team
      collaboration in OOHC. A clearer description of professional team roles should be
      provided.

PMID- 29184418
TI  - FGF2 promotes metastasis of uveal melanoma cells via store-operated calcium
      entry.
AB  - Uveal melanoma (UM), the most common primary intraocular malignancy in adults, is
      highly metastatic and associated with dismal prognosis. Fibroblast growth factor
      2 (FGF2) has been shown to induce cell proliferation and angiogenesis of melanoma
      and other malignancies. However, the expression of FGF2 in UM and its effects on
      melanoma cell migration are not well known. In this study, we found FGF2
      expression was related to UM histological subtype and presence of metastasis. In
      vitro experiments showed that FGF2 treatment caused increased horizontal and
      vertical migration and F-actin cytoskeleton assembly as well as decreased
      adhesive activity of MUM2B cells, together with increased intracellular calcium
      concentration and expression of ORAI1 and STIM1 - two key regulatory proteins of
      store-operated calcium entry (SOCE). The mouse xenograft model showed that MUM2B
      cells with FGF2 stimulation grew into larger tumor masses and were prone to
      metastasis. In addition, the SOCE inhibitor 2-aminoethoxydiphenyl borate (2-APB)
      reversed all of these effects of FGF2. Finally, human UM samples and mouse
      xenograft model samples were used to confirm the correlation of FGF2 with ORAI1
      and STIM1 expression. Taken together, our study suggests that FGF2 promotes
      metastasis of UM via SOCE.

PMID- 29184419
TI  - Interleukin-6 upregulates SOX18 expression in osteosarcoma.
AB  - Aim: SOX18 is a potential oncogene in osteosarcoma via controlling osteosarcoma
      cell proliferation and metastasis. Interleukin-6 (IL-6), a major activator of
      Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3
      (STAT3) signaling, plays an important role in the growth of carcinoma cells. The
      present study aims to investigate the correlation between IL-6 and SOX18 in
      osteosarcoma. Materials and methods: Protein expression and mRNA expression were
      determined by Western blot and real-time polymerase chain reaction (PCR)
      analysis, respectively. Cell proliferation and apoptosis were identified by Cell
      Counting Kit-8 assay and flow cytometry analysis, respectively. Results: We found
      that SOX18, IL-6 and p-STAT3 were elevated in osteosarcoma compared with bone
      cyst tissues. A positive correlation between the mRNA levels of IL-6 and SOX18
      was observed in osteosarcoma tissues. IL-6 stimulation dose dependently induced
      the mRNA and protein levels of SOX18 in U-2OS and MG63 cells. Furthermore, IL-6
      significantly rescued the inhibitory and induction effects of SOX18 knockdown on
      osteosarcoma cell proliferation and apoptosis, respectively. The changes in cell
      proliferation (PCNA) and apoptosis-related proteins (Bcl-2, Bax and Cleaved
      Caspase 3) were in line with the results of cell proliferation and apoptosis
      assays. Conclusion: Our data suggest that IL-6 is a possible upstream regulator
      for SOX18 in osteosarcoma.

PMID- 29184420
TI  - Amatuximab and novel agents targeting mesothelin for solid tumors.
AB  - Mesothelin (MSLN) is considered a promising target for cancer therapy. Originally
      extracted in 1992 after the immunization of mice with a human ovarian cancer (OC)
      cell line and cloned in 1996, MSLN seems to be involved in cell adhesion and
      metastasis. MSLN is prevalent in mesothelia tissues but is expressed in several
      human cancers, such as OC, pancreatic cancer, mesothelioma, and lung cancer.
      Amatuximab (MORAb-009) is a mouse-human chimeric monoclonal antibody with a
      selective affinity for MSLN. The principal mechanism of action comprises
      inhibition of binding of MSLN with the antigen CA125/MUC16. The highest phase of
      development is actually a Phase II trial (MORAb-009-201, Europe). In this review,
      we describe the mechanism of action of amatuximab and other MSLN-targeting novel
      drugs, along with a discussion about the expected efficacy, safety, and toxicity
      of this promising group of agents and implications for future research and
      clinical practice.

PMID- 29184421
TI  - LncRNA expression and implication in osteosarcoma: a systematic review and meta
      analysis.
AB  - Purpose: Osteosarcoma is the most prevalent primary bone tumor in children,
      adolescents, and older adults, typically presenting with poor survival outcomes.
      In recent years, ample evidence has shown that many long noncoding RNAs (lncRNAs)
      have been aberrantly expressed in osteosarcoma, demonstrating their potential to
      serve as prognostic markers. In this study, we performed a meta-analysis on four
      lncRNAs (TUG1, UCA1, BCAR4, and HULC) to systematically evaluate their prognostic
      value in osteosarcoma. Materials and methods: The eligible articles were
      systematically searched in PubMed, Web of Science, Embase, and Elsevier
      ScienceDirect (up to September 22, 2017), and one meta-analysis concerning the
      association between lncRNA expression and the overall survival (OS) of
      osteosarcoma patients was performed. Survival outcomes were analyzed by OS.
      Subgroup analyses were performed. Results: A total of 1,361 patients with
      osteosarcoma and 12 lncRNAs from 16 articles were included in the study. Of the
      listed lncRNAs, the high expression of 10 lncRNAs indicated worse survival
      outcomes, while only two lncRNAs were shown to positively affect patients' OS.
      Conclusion: This meta-analysis indicated that the abnormally expressed lncRNAs
      might significantly affect the survival of osteosarcoma patients. Combined use of
      these lncRNAs may serve as potential novel biomarkers for the indication of
      clinical outcomes of osteosarcoma patients as well as the selection of adjuvant
      chemotherapy strategies for clinical treatment of this disease.

PMID- 29184424
TI  - Erratum: Drug treatment of type 2 diabetes mellitus in patients for whom
      metformin is contraindicated [Corrigendum].
AB  - [This corrects the article on p. 15 in vol. 7, PMID: 24465132.].

PMID- 29184422
TI  - Prevalence of hepatitis C virus-resistant association substitutions to direct
      acting antiviral agents in treatment-naive hepatitis C genotype 1b-infected
      patients in western China.
AB  - Background: Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) are
      potent and highly efficacious. However, resistance-associated substitutions
      (RASs) relevant to DAAs can impair treatment effectiveness even at baseline.
      Moreover, the prevalence of baseline RASs in HCV genotype 1b-infected patients in
      western China is still unclear. Materials and methods: Direct sequencing of the
      HCV NS3, NS5A, and NS5B regions was performed in baseline serum samples of 70
      DAAs treatment-naive HCV 1b-infected patients in western China. The sequences
      were analyzed with MEGA version 5.05 software. Evolutionary patterns of RASs and
      amino-acid covariance patterns in the NS3, NS5A, and NS5B genes were analyzed by
      MEGA and Cytoscape (version 3.2.1), respectively. Results: The presence of at
      least one RAS in the NS3 region (C16S, T54S, Q80R/L, A87T, R117H, S122G, V132I,
      V170I) was observed in 85.48% (53 of 62) of patients, RASs in the NS5A region
      (L28M, R30Q, Q54H, P58S/T, Q62H/R, Y93H) were observed in 42.42% (28 of 66) of
      patients, and RASs in the NS5B region (N142S, A300T, C316N, A338V, S365A, L392I,
      M414L, I424V, A442T, V499A, S556G) were observed in 100% (44 of 44) of patients.
      Evolutionary patterns of RASs and amino-acid covariance patterns for the NS3,
      NS5A, and NS5B genes are reported. Conclusion: The prevalence of RASs relevant to
      DAAs detected in the NS3, NS5A, and NS5B regions of HCV 1b from DAA treatment
      naive patients is high. Therefore, more attention should be paid to RASs
      associated with DAAs in the upcoming DAA-treatment era in China.

PMID- 29184423
TI  - Propofol or benzodiazepines for short- and long-term sedation in intensive care
      units? An economic evaluation based on meta-analytic results.
AB  - Purpose: This evaluation compares propofol and benzodiazepine sedation for
      mechanically ventilated patients in intensive care units (ICUs) in order to
      identify the potential economic benefits from different payers' perspectives.
      Methods: The patient-level simulation model incorporated efficacy estimates from
      a structured meta-analysis and ICU-related costs from Italy, Germany, France, UK,
      and the USA. Efficacy outcomes were ICU length of stay (LOS), mechanical
      ventilation duration, and weaning time. We calculated ICU costs from mechanical
      ventilation duration and ICU LOS based on national average ICU costs with and
      without mechanical ventilation. Three scenarios were investigated: 1) long-term
      sedation >24 hours based on results from randomized controlled trials (RCTs); 2)
      long-term sedation based on RCT plus non-RCT results; and 3) short-term sedation
      <24 hours based on RCT results. We tested the model's robustness for input
      uncertainties by deterministic (DSA) and probabilistic sensitivity analyses
      (PSA). Results: In the base case, mean savings with propofol versus
      benzodiazepines in long-term sedation ranged from ?406 (95% confidence interval
      [CI]: 646 to 164) in Italy to 1,632 ? (95% CI: 2,362 to 880) in the USA.
      Inclusion of non-RCT data corroborated these results. Savings in short-term
      sedation ranged from ?148 (95% CI: 291 to 2) in Italy to ?502 (95% CI: 936 to 57)
      in the USA. Parameters related to ICU and mechanical ventilation had a stronger
      influence in the DSA than drug-related parameters. In PSA, propofol reduced costs
      and ICU LOS compared to benzodiazepines in 94%-100% of simulations. The largest
      savings may be possible in the UK and the USA due to higher ICU costs.
      Conclusion: Current ICU sedation guidelines recommend propofol rather than
      midazolam for mechanically ventilated patients. This evaluation endorses the
      recommendation as it may lead to better outcomes and savings for health care
      systems, especially in countries with higher ICU-related costs.

PMID- 29184425
TI  - Obesity and morbid obesity associated with higher odds of hypoalbuminemia in
      adults without liver disease or renal failure.
AB  - Background and objective: Studies are needed in order to inform recommendations
      for interpreting albumin levels among obese individuals without known medical
      conditions associated with hypoalbuminemia. The objective of this study was to
      examine the association of obese and morbidly obese status with hypoalbuminemia,
      while adjusting for age, sex, diabetes, prediabetes, diabetic nephropathy, and
      nephrotic syndrome. Patients and methods: Retrospective data collection from
      adult patients presenting to the outpatient Endocrinology and Metabolism Clinic
      was performed between January 2015 and December 2015. An initial sample of 180
      patients was selected. After excluding patients who were younger than 18 years,
      who had known cases of liver disease or renal failure, or who had missing data, a
      final sample of 122 subjects was identified. Serum albumin and objectively
      measured weight and height data were retrieved from hospital records. A board
      certified endocrinologist reviewed patient records to identify the presence of
      renal and diabetic conditions. Descriptive statistics were used to examine sample
      characteristics. Multiple logistic regression analysis was used to examine the
      association of obesity and morbid obesity with hypoalbuminemia (serum albumin <
      34 g/L) while adjusting for age, sex, diabetes, prediabetes, diabetic
      nephropathy, and nephrotic syndrome. Results: Approximately 43% of the sample
      were categorized as obese and 13% were categorized as morbidly obese. The mean
      serum albumin level was 38.00 g/L (standard deviation [SD] = 4.26) among subjects
      who were neither overweight nor obese, 38.35 g/L (SD = 0.48) among overweight
      subjects, 34.57 g/L (SD = 4.71) among obese subjects, and 33.81 g/L (SD = 3.71)
      among morbidly obese subjects. Adjusting for age, sex, diabetes, prediabetes,
      nephrotic syndrome, and diabetic nephropathy, obese subjects had significantly
      higher odds of hypoalbuminemia (odds ratio [OR]: 4.10, 95% confidence interval
      [CI]: 1.50-11.27, P-value = 0.006), as did morbidly obese subjects (OR: 6.94, 95%
      CI: 1.91-25.23, P-value = 0.003). Conclusion: The findings suggest that obesity
      and morbid obesity can be considered as independent predictors of
      hypoalbuminemia. The findings can be used to inform future studies aiming to
      better understand the association of obesity and morbid obesity with
      hypoalbuminemia and to help inform guidelines for clinicians on how to correctly
      interpret and utilize serum albumin data for obese individuals.

PMID- 29184426
TI  - Recommendations for volume augmentation and rejuvenation of the face and hands
      with the new generation polycaprolactone-based collagen stimulator (Ellanse(r)).
AB  - Background: The range of fillers currently available for soft-tissue augmentation
      is constantly expanding. The latest advances in filler technology include
      collagen biostimulators that exert their esthetic effect by promoting
      neocollagenesis. One such product is the next-generation collagen biostimulator
      (Ellanse(r)) that demonstrates properties as yet unseen in soft-tissue fillers.
      It is composed of polycaprolactone (PCL) microspheres in an aqueous
      carboxymethylcellulose gel carrier. Given its specific characteristics and the
      number of areas that can be treated with this innovative product, experts'
      recommendations were deemed necessary and are therefore presented in this paper
      with a specific focus on the indications, treatment areas and procedures as well
      as injection techniques. Methods: A multinational, multidisciplinary group of
      plastic surgeons and dermatologists convened to develop recommendations with a
      worldwide perspective. This publication provides information on the specific
      characteristics of the product and focuses on the recommendations on the
      injection techniques. Results: Recommendations on injection techniques are
      provided for the upper face, mid-face and lower face and zone by zone for each of
      these areas, as well as hands. Based on the particular anatomy of each area, the
      focus is on the techniques and devices of injection and the volume and depth of
      injection. The information is tabulated, and photos are presented for
      illustration. Conclusion: These recommendations provide a guideline for
      physicians who wish to perform safe and efficacious treatment with the PCL
      collagen stimulator for face and rejuvenation with volume augmentation.

PMID- 29184427
TI  - Pemphigoid gestationis: current perspectives.
AB  - Many skin diseases can occur in pregnant women. However, a few pruritic
      dermatological conditions are unique to pregnancy, including pemphigoid
      gestationis (PG). As PG is associated with severe morbidity for pregnant women
      and carries fetal risks, it is important for the clinician to quickly recognize
      this disease and refer it for dermatological evaluation and treatment. Herein, we
      review the pathogenesis, clinical characteristics, and management of PG.

PMID- 29184429
TI  - Topical application of ST266 reduces UV-induced skin damage.
AB  - Ultraviolet radiation (UVR) has a significant impact on human skin and is the
      major environmental factor for skin cancer formation. It is also believed that
      80% of the signs of skin aging are attributed to UVR. UVR induces inflammatory
      changes in the skin via the increase in oxidative stress, DNA damage vascular
      permeability, and fluctuation in a myriad of cytokines. Acutely, UVR causes skin
      inflammation and DNA damage, which manifest as sunburn (erythema). ST266 is the
      secretome of proprietary amnion-derived cells that have been shown to reduce
      inflammation and accelerate healing of various wounds by promoting migration of
      keratinocytes and fibroblasts in preclinical animal studies. We hypothesized that
      ST266 has anti-inflammatory effects that can be used to reduce ultraviolet (UV)
      erythema and markers of inflammation. In this study, we examined the in vivo
      effects of ST266 on post UV-irradiated skin by measuring erythema, level of
      cyclobutane pyrimidine dimer (CPD), and expression level of xeroderma
      pigmentosum, complementation group A (XPA). We demonstrated that ST266 has the
      potential to reduce the acute effects of UV-induced skin damage when applied
      immediately after the initial exposure. In addition, ST266 is shown to reduce
      erythema, increase XPA DNA repair protein, and decrease damaged DNA.

PMID- 29184428
TI  - Management of refractory pityriasis rubra pilaris: challenges and solutions.
AB  - Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory papulosquamous skin
      disease. Its clinical presentation and evolution is very variable. The most
      frequent clinical features are follicular papules, progressing to yellow-orange
      erythroderma with round small areas of normal skin and the well-demarcated
      palmoplantar keratoderma. Actually, six different types of PRP have been
      described based on clinical characteristics, age of onset, and prognosis. The
      pathogenesis is still unknown, and treatment can be challenging. Available
      treatments are mainly based on case reports or case series of clinical experience
      because no controlled randomized trials have never been performed because of the
      rarity of the condition. Traditional systemic treatment consists in retinoids,
      which are actually considered as first-line therapy, but refractory cases that do
      not respond or relapse after drug interruption do exist. In recent years,
      numerous reports have demonstrated the efficacy of new agents such as biological
      drugs. This article is an overview on available therapeutic options, in
      particular for refractory forms of PRP.

PMID- 29184430
TI  - Evaluation of a fecal immunochemistry test prior to colonoscopy for outpatients
      with various indications.
AB  - Background: Stool tests can predict advanced neoplasms prior to colonoscopy.
      Results of immunochemical stool tests to predict findings at colonoscopy for
      various indications are less often reported. We compared pre-colonoscopy stool
      tests with findings in patients undergoing colonoscopy for different indications.
      Patients and methods: Charts of patients undergoing elective or semi-urgent
      colonoscopy were reviewed. Comparison of adenoma detection rates and pathological
      findings was made between prescreened and non-prescreened, and between stool
      positive and stool-negative cases. Demographics, quality of colonoscopy, and
      pathological findings were recorded. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were assessed. Statistical significance was accepted at p<=0.05.
      Results: Charts of 325 patients were reviewed. Among them, stool tests were done
      on 144 patients: 114 were negative and 30 were positive. Findings were similar in
      the pretest and non-pretest groups. Detection of advanced adenomas per patient
      was higher in the stool-positive group compared to the stool-negative group
      (23.4% vs 3.5%, p=0.0016, OR =7.6 [95% CI: 2-29.3]). Five advanced adenomas
      (without high-grade dysplasia or adenocarcinoma) and several cases of multiple
      adenomas were missed in the negative group. Sensitivity and specificity for
      advanced polyps was 63.6% and 82.7%, respectively. The negative predictive value
      was 96.5%. Male gender was independently predictive of any adenoma. Conclusion:
      The stool immunochemical test best predicted advanced neoplasms and had a high
      negative predictive value in this small cohort. Whether this test can be applied
      to determine the need for colonoscopy in groups other than average risk would
      require more studies.

PMID- 29184431
TI  - Update on the clinical utility of an RNA interference-based treatment: focus on
      Patisiran.
AB  - RNA interference (RNAi) is a naturally existing endogenous mechanism for post
      transcriptional gene regulation, nowadays commonly utilized for functional
      characterization of genes and development of potential treatment strategies for
      diseases. RNAi-based studies for therapy, after being examined for over a decade,
      are finally in the pipeline for developing a potential treatment for the mutated
      transthyretin (TTR) gene, which gives rise to a dysfunctional TTR protein. This
      dysfunctional protein causes TTR amyloidosis (ATTR), an inherited, progressively
      incapacitating, and often fatal genetic disorder. TTR is a protein produced in
      the liver, and functions as a carrier for retinol-binding protein and also
      thyroxine. This protein facilitates the transport of vitamin A around the human
      body. A mutation or misprint in the code of this protein results in an abnormal
      folding of the protein. Therefore, not only does the transportation of the
      vitamin A become disabled, but also there will be formation of clusters called
      amyloid deposits, which attack the heart and the nerves causing some patients to
      be unconditionally bound to bed. ATTR is a hereditary autosomal dominant disease
      with a 50% chance of inheritance by offspring, even with just one of the parents
      having a single defective allele of this gene. Alnylam Pharmaceuticals worked on
      the concept of RNAi therapy for years, which led to the introduction of lipid
      nanoparticles encircling small interfering RNAs. The drug showed extremely
      positive results since the first trial, and a great percentage of defective
      protein reduction. This drug was later named Patisiran.

PMID- 29184432
TI  - Role of magnetic resonance planimetry and magnetic resonance parkinsonism index
      in discriminating Parkinson's disease and progressive supranuclear palsy: a
      retrospective study based on 1.5 and 3 T MRI.
AB  - Objective: The objective of the study was to assess magnetic resonance (MR)
      planimetric measurements and MR parkinsonism index (MRPI) in differentiating
      progressive supranuclear palsy (PSP) from Parkinson's disease (PD) using 1.5 and
      3 T MRI scanner. Subjects and methods: After ethical approval was obtained,
      analysis of 34 consecutive patients with PSP, 34 patients with PD and 34 healthy
      controls (HCs) was performed. HCs were age-matched adults without any history of
      neurodegenerative disease or movement disorders. Retrospective data from the past
      10 years (from January 2006 to December 2015) were obtained from the Hospital
      Information Management System, and informed consent was obtained from all
      participants. The measurements of pons area-midbrain area ratio (P/M) and MCP
      width-superior cerebellar peduncle (SCP) width ratio (MCP/SCP) were used, and
      MRPI was calculated by the formula ([P/M]*[MCP/SCP]). Results: Midbrain area and
      SCP width in patients with PSP (19 males, 15 females; mean age =66.7 years) were
      significantly (P<0.001) smaller than in patients with PD (20 males, 14 females;
      mean age =66.7 years) and control participants (17 males, 17 females; mean age
      =66.1 years). P/M and MCP/SCP were significantly higher in patients with PSP than
      in patients with PD and control participants. All measurements showed some
      overlap of values between patients with PSP and patients from PD group and
      control participants. MRPI value was significantly higher in patients with PSP
      (mean 21.00) than in patients with PD (mean 9.50; P<0.001) and control
      participants (mean 9.6; P<0.001), without any overlap of values among groups. No
      correlation was found between the duration of disease, PSP rating scale, PSP
      staging system and MRPI in this study. No patient with PSP received a
      misdiagnosis when the index was used (sensitivity and specificity, 100%).
      Conclusion: MRPI should be made an essential part of all MRI brain reporting
      whenever differentiation between PD and PSP is sought for.

PMID- 29184433
TI  - Diagnosis and treatment of irritable bowel syndrome with predominant constipation
      in the primary-care setting: focus on linaclotide.
AB  - Irritable bowel syndrome (IBS) is a complex functional gastrointestinal disorder
      that is exceedingly common in clinical practice. IBS with predominant
      constipation (IBS-C) is a subtype of IBS that accounts for more than a third of
      the IBS diagnosed. Diagnosis of IBS requires a careful personalized approach, a
      comprehensive clinical history, limited but relevant investigations, and
      continued follow-up. Major IBS societies and guidelines recommend offering a
      positive diagnosis of IBS based on presenting symptomatology. Abdominal pain that
      may or may not be relieved by defecation is the cardinal symptom of IBS;
      distension and bloating are other common symptoms. Careful attention should be
      paid to alarm symptoms before a diagnosis of IBS is made. Pharmacotherapy with
      linaclotide is recommended for moderate-severe IBS-C, based on high-quality
      evidence from randomized controlled trials. Diarrhea is the major side effect of
      linaclotide, and limited cost-effectiveness data currently exist.

PMID- 29184434
TI  - Manifestation of non-ST elevation myocardial infarction due to hyperthyroidism in
      an anomalous right coronary artery.
AB  - Introduction: Anomalous origin of the right coronary artery (RCA) from the left
      coronary cusp of the aorta is a moderately rare but potentially life-threatening
      incident. Myocardial infarction (MI) and sudden cardiac death have been described
      with this anomaly, especially in those who engage in excessive exercise. However,
      this case study shows this incidence in association with hyperthyroidism. Case
      description: A previously healthy 51-year-old female with history of
      hypothyroidism presented with acute onset chest pain for 1 day. Patient's
      electrocardiogram was normal, however, she had elevated troponins and given her
      typical chest pain, she was diagnosed with acute coronary syndrome (ACS). The
      patient had been on levothyroxine and was found to have a subnormal thyroid
      stimulating hormone level suggesting hyperthyroidism. Echocardiogram was normal.
      Coronary angiogram showed an anomalous RCA arising from the left coronary cusp of
      the sinus of Valsalva and no evidence of atherosclerosis. A coronary computed
      tomography angiogram was done confirming this finding and showed a slit-like
      deformity of the coronary ostium with at least 50% luminal stenosis. The patient
      was referred to a cardiothoracic surgeon for potential coronary artery bypass
      graft. Discussion: This case illustrates a rare presentation of ACS due to
      hyperthyroidism in an anomalous RCA. MI is a rare manifestation of
      hyperthyroidism, but in combination with an anatomical defect, it can potentiate
      adverse outcomes. The mechanisms by which thyroid hormones influence
      cardiovascular hemodynamics are by causing a hyperdynamic circulatory state,
      increasing myocardial oxygen demand, and increasing the risk of coronary
      vasospasm. The combination of anatomic and metabolic defects is what likely
      precipitated this patient's outcome.

PMID- 29184435
TI  - Prevalence and association of vitamin D deficiency and mortality in patients with
      severe sepsis.
AB  - Background: Vitamin D is a steroid prohormone that regulates body calcium and
      phosphate metabolism. Recent studies have shown an association between low
      vitamin D status and high mortality in patients admitted to intensive care units.
      To date, there are limited data available specifically about severely septic
      patients in medical units. Objectives: To determine the prevalence of vitamin D
      deficiency in severely septic patients and its clinical outcomes, including
      mortality rate. Methods: A prospective observational study was conducted to
      investigate the prevalence of vitamin D deficiency and its association with 30
      day mortality in patients with severe sepsis. Patients admitted to medical wards
      at our hospital between November 2014 and March 2015 were included in the study.
      A 25-hydroxyvitamin D level <20 ng/mL was defined as vitamin D deficiency, and
      <12 ng/mL as severe deficiency. For an association analysis, the patients were
      grouped into deficient versus not deficient and severely deficient versus not
      severely deficient. Results: One hundred and ten eligible patients were enrolled.
      A total of 83 patients (75%) had vitamin D deficiency and 42 (38%) had severe
      deficiency. Despite an insignificant higher 30-day hospital mortality rate in
      vitamin D deficient versus non-deficient groups (16% vs 4%, p=0.18), the
      differences were significant between the severely deficient versus non-severe
      groups (23% vs 4%, p=0.02). The odds ratio of the 30-day mortality rate was 4.83
      (95% confidence interval [CI], 0.60-38.77, p=0.14) for vitamin D deficiency and
      7.69 (95% CI, 2.00-29.55, p=0.003) for severe deficiency. Conclusion: The
      prevalence of vitamin D deficiency was very high in three-quarters of patients
      with severe sepsis. A significant higher mortality rate was observed,
      particularly in patients with severe vitamin D deficiency.

PMID- 29184436
TI  - Continuous wound infusion with chloroprocaine in a pig model of surgical lesion:
      drug absorption and effects on inflammatory response.
AB  - Continuous wound infusion (CWI) may protect from inflammation, hyperalgesia and
      persistent pain. Current local anesthetics display suboptimal pharmacokinetic
      profile during CWI; chloroprocaine (CP) has ideal characteristics, but has never
      been tested for CWI. We performed an animal study to investigate the
      pharmacokinetic profile and anti-inflammatory effect of CP during CWI. A total of
      14 piglets received an infusion catheter after pararectal laparotomy and were
      randomly allocated to one of three groups: 5 mL/h infusion of saline (group A),
      CP 1.5% (group B) and CP 0.5% (group C). Blood sampling was performed to assess
      absorption and systemic inflammation at 0, 3, 6, 12, 24, 48, 72, 96, 102 and 108
      hours. The wound and contralateral healthy abdominal wall were sampled for
      histological analyses. Absorption of CP from the site of infusion, evaluated as
      the plasmatic concentrations of CP and its metabolite, 4-amino-2-chlorobenzoic
      acid (CABA), showed a peak during the first 6 hours, but both CP and its
      metabolite rapidly disappeared after stopping CP infusion. Local inflammation was
      reduced in groups B and C (CP-treated p < 0.001), in a CP dose-dependent fashion.
      While CP inhibited in a dose-dependent manner pig mononuclear cells (MNCs) in
      vitro proliferation to a polyclonal activator, no effect on systemic cytokines'
      concentrations or on ex vivo monocytes' responsiveness was observed, suggesting
      the lack of systemic effects, in line with the very short half-life of CP in
      plasma. CP showed a very good profile for use in CWI, with dose-dependent local
      anti-inflammatory effects, limited absorption and rapid clearance from the
      bloodstream upon discontinuation. No cytotoxicity or side effects were observed.
      CP, therefore, may represent an optimal choice for clinical CWI, adaptable to
      each patient's need, and protective on wound inflammatory response (and
      hyperalgesia) after surgery.

PMID- 29184437
TI  - Antiallodynic and antihyperalgesic activities of zerumbone via the suppression of
      IL-1beta, IL-6, and TNF-alpha in a mouse model of neuropathic pain.
AB  - Background: Neuropathic pain is a debilitating condition that severely affects
      the quality of life for those with this pain condition, and treatment for pain
      relief is greatly sought-after. Zerumbone (Zer), a sesquiterpene compound
      isolated from the rhizomes of a Southeast Asian ginger plant, Zingiber zerumbet
      (L.) Roscoe ex Smith. (Zingiberaceae), showed antinociceptive and
      antiinflammatory properties when previously tested on models of nociception and
      inflammation. Objective: This study investigated the effects of prophylactic
      administration of zerumbone on allodynia and hyperalgesia in a mouse model of
      chronic constriction injury (CCI)-induced neuropathic pain. Methods:
      Intraperitoneal administration of Zer (5-50 mg/kg) from day 1 post-surgery was
      carried out to identify the onset and progression of the pain condition.
      Responses toward mechanical and cold allodynia, and mechanical and thermal
      hyperalgesia were assessed on days 3, 5, 7, 9, 11, and 14 post-surgery. Blood
      plasma and spinal cord levels of interleukin (IL)-1beta, IL-6, tumor necrosis
      factor-alpha, and IL-10 were screened using enzyme-linked immunosorbent assay on
      day 15. Results: Zer (10 and 50 mg/kg) attenuated pain symptoms on all days of
      behavioral testing without any signs of sedation in the rotarod test. ED50 values
      for mechanical allodynia, cold allodynia, thermal hyperalgesia, and mechanical
      hyperalgesia were 9.25, 9.507, 8.289, and 9.801 mg/kg, respectively. Blood plasma
      and spinal levels of IL-1beta, IL-6, and tumor necrosis factor-alpha but not IL
      10 were significantly (p<0.05) suppressed by zer treatment. Discussion and
      conclusion: Zer exhibits its antiallodynic and antihyperalgesic properties via
      reduced sensitization at nociceptor neurons possibly through the suppression of
      inflammatory mediators. Zer may prove to be a novel and beneficial alternative
      for the management of neuropathic pain.

PMID- 29184438
TI  - Efficacy of local dexmedetomidine add-on for spermatic cord block anesthesia in
      patients undergoing intrascrotal surgeries: randomized controlled multicenter
      clinical trial.
AB  - Study objective: The objective of this study was to evaluate the effect of adding
      dexmedetomidine (DEX) to bupivacaine on the quality of spermatic cord block
      anesthesia and postoperative analgesia. Design: This is a randomized, double
      blind study. Setting: This study was performed in an educational and research
      hospital. Patients: One hundred twenty adult males were scheduled for
      intrascrotal surgeries. Interventions: Patients were divided into two groups:
      group B received 10 mL of bupivacaine 0.25% for spermatic cord block and
      intravenous 50 ug of DEX and group BD received 10 mL of bupivacaine 0.25% added
      to 50 ug of DEX (9.5 mL bupivacaine 0. 25% + 0.5 mL [50 ug] DEX) for spermatic
      cord block, and for masking purposes, the patients received isotonic saline
      intravenously. Measurements: Time to first analgesic request, analgesic
      consumption, and visual analog scale (VAS) pain score in the first 24 hours
      postoperatively were assessed. Main results: Time to first rescue analgesic was
      significantly delayed in group BD in comparison with group B, median
      (interquartile) range, 7 (6-12) hours versus 6 (5-7) hours, (p=0.000), the mean
      cumulative morphine consumption (mg) in the first postoperative 24 hours was
      significantly lower in group BD compared with group B, 8.13+/-4.45 versus 12.7+/
      3.79, with a mean difference (95% CI) of -4.57 (-6.06 to -3.07) (p=0.000); also,
      there was a significant reduction of VAS pain score in group BD in comparison
      with group B at all measured time points, VAS 2 hours (1.28+/-0.9 vs 1.92+/-0.8),
      VAS 6 hours (2.62+/-1.5 vs 3.93+/-1.2), VAS 12 hours (2.40+/-1.1 vs 3.57+/-0.65),
      VAS 24 hours (1.90+/-0.68 vs 2.53+/-0.62) (p=0.000). Conclusion: The addition of
      50 ug of DEX to bupivacaine 0.25% in spermatic cord block for intrascrotal
      surgeries resulted in delay of first analgesic supplementation, reduction of
      postoperative analgesic consumption as well as improvement of the success rate of
      the block.

PMID- 29184439
TI  - Ultrasound-guided rectus sheath block, caudal analgesia, or surgical site
      infiltration for pediatric umbilical herniorrhaphy: a prospective, double
      blinded, randomized comparison of three regional anesthetic techniques.
AB  - Background: Umbilical hernia repair is a common pediatric surgical procedure.
      While opioid analgesics are a feasible option and have long been a mainstay in
      the pharmacological intervention for pain, the effort to improve care and limit
      opioid-related adverse effects has led to the use of alternative techniques,
      including regional anesthesia. The current study prospectively compares the
      analgesic efficacy of three techniques, including caudal epidural blockade,
      peripheral nerve blockade, and local wound infiltration, in a double-blinded
      study. Patients and methods: A total of 39 patients undergoing umbilical hernia
      repair were randomized to receive a caudal epidural block (CDL), ultrasound
      guided bilateral rectus sheath blocks (RSB), or surgical site infiltration (SSI)
      with local anesthetic. Intraoperative anesthetic care was standardized, and
      treatment groups were otherwise blinded from the intraoperative anesthesiology
      team and recovery nurses. Postoperatively, the efficacy was evaluated using
      Hannallah pain scores, Aldrete recovery scores, the need for intravenous
      fentanyl, and the time to discharge. Results: Each cohort was similar in terms of
      age, weight, premedication dosing, length of case, intraoperative and
      postoperative fentanyl requirements, and time to tracheal extubation. Among the
      three cohorts, there were no significant differences noted in terms of pain
      scores or time to recovery. Conclusion: All the three techniques provided
      effective analgesia following umbilical hernia repair. Our findings offer
      effective and safe analgesic options as alternatives to the neuraxial (caudal)
      approach.

PMID- 29184440
TI  - Administration of epidural labor analgesia is not associated with a decreased
      risk of postpartum depression in an urban Canadian population of mothers: a
      secondary analysis of prospective cohort data.
AB  - Background: Postpartum depression (PPD) is a common complication of pregnancy,
      affecting approximately 13% of mothers internationally. Previous research has
      examined whether epidural analgesia used for pain control during labor and birth
      is associated with a lower risk of PPD, but reports conflicting results and may
      have suffered from methodological shortcomings. Our study aimed to prospectively
      assess whether epidural analgesia is associated with a lower risk of PPD (at
      either 6 weeks or 6 months postpartum) after attempting to adequately adjust for
      selection bias and confounding variables. Methods: We conducted a secondary
      analysis of a prospective cohort of urban Canadian mothers who were recruited at
      birth in Calgary, Canada, in 2010, for a primary study on predictors of PPD.
      Mothers with full-term, singleton infants who did not require neonatal intensive
      care unit admission of >24 hours were included, and filled out questionnaires at
      birth, 6 weeks and 6 months postpartum including demographics, birth data,
      maternal and infant physical health, lifestyle, breastfeeding and maternal mental
      health. Descriptive statistics were calculated for participant characteristics
      and to identify potential confounder variables. Multivariable logistic regression
      analysis was conducted to assess whether epidural analgesia is associated with
      PPD after controlling for available confounding variables. Results: Our study
      included 206 mothers who had vaginal deliveries and were free of depression at
      delivery. We found an incidence of PPD of 13.3% (n=27) and no statistically
      significant association between epidural use and PPD, regardless of adjustment
      for potential confounding variables (unadjusted odds ratio [OR] 0.86, 95%
      confidence interval [CI] 0.69-1.22; adjusted OR (for body mass index 1.04, 95% CI
      0.40-2.77). Conclusion: We did not observe a significant association between
      epidural use and PPD. While the CIs are wide, we do not believe that this masks a
      clinically relevant association, and as such, the risks and benefits of epidural
      analgesia communicated to women during labor and delivery should not be modified.

PMID- 29184441
TI  - Potential role of radiation therapy in augmenting the activity of immunotherapy
      for gynecologic cancers.
AB  - Immune checkpoint inhibitors have become an area of intense interest in oncology
      and are actively being studied in a variety of cancer types with a wide range of
      success. In vitro data suggest mechanisms by which radiation can activate the
      immune system, and ongoing studies are exploring the potential interaction of
      checkpoint inhibitors with radiotherapy in both preclinical and clinical
      settings. Gynecologic malignancies are a heterogeneous group of tumors with
      varying prognoses, intrinsic immunogenicity, and potential for response to immune
      based therapies. In this review, we focus on the rationale for immunotherapy and
      opportunities for augmentation by photon radiotherapy in cancers of the cervix,
      endometrium, and ovary.

PMID- 29184442
TI  - Exome and transcriptome sequencing identifies loss of PDLIM2 in metastatic
      colorectal cancers.
AB  - Background: Understanding the genomic determinants associated with metastasis in
      colorectal cancers (CRCs) provides crucial clues for improving patient care.
      Patients and methods: In this study, we performed whole-exome sequencing as well
      as RNA sequencing analyses on five pairs of primary and liver metastasized
      samples from CRC patients together with blood/normal control samples for each
      pair. Results: We identified genomic deletions in the region of 8p21-23 (q value
      <0.01) from analysis of recurrent regions with copy number variations in both
      primary and matched metastatic lesions. Consistent with this result, we found
      significantly decreased expression levels of all 12 genes (ADAMDEC1, C8orf80,
      CLDN23, EPHX2, GFRA2, NEFL, NEFM, PDLIM2, PTK2B, SCARA5, SLC18A1 and STMN4)
      located within this region (adjusted P<0.01). Notably, the mRNA levels of PDLIM2,
      a key regulator of well-known cancer-associated genes including the proto
      oncogene c-MYC, an early response gene IER3, and regulators of apoptosis such as
      BCL2, FAS, and FASLG, were highly downregulated in tumors compared to normal
      tissues. Conclusion: Taken together, our findings uncovered various genomic
      alterations potentially leading to metastasis in CRC and provide important
      insights into the development of potential therapeutic targets for preventing
      metastatic progression of CRC.

PMID- 29184443
TI  - Training surgeons in shared decision-making with cancer patients aged 65 years
      and older: a pilot study.
AB  - Objective: Treatment decision-making in older patients with colorectal (CRC) or
      pancreatic cancer (PC) needs improvement. We introduced the EASYcare in Geriatric
      Onco-surgery (EASY-GO) intervention to optimize the shared decision-making (SDM)
      process among these patients. Methods: The EASY-GO intervention comprised a
      working method with geriatric assessment and SDM training for surgeons. A non
      equivalent control group design was used. Newly diagnosed CRC/PC patients aged
      >=65 years were included. Primary patient-reported experiences were the quality
      of SDM (SDM-Q-9, range 0-100), involvement in decision-making (Visual Analog
      Scale for Involvement in the decision-making process [range 0-10]), satisfaction
      about decision-making (Visual Analog Scale for Satisfaction concerning the
      decision-making process [range 0-10]), and decisional regret (Decisional Regret
      Scale [DRS], range 0-100). Only for DRS, lower scores are better. Results: A
      total of 71.4% of the involved consultants and 42.9% of the involved residents
      participated in the EASY-GO training. Only 4 trained surgeons consulted patients
      both before (n=19) and after (n=19) training and were consequently included in
      the analyses. All patient-reported experience measures showed a consistent but
      non-significant change in the direction of improved decision-making after
      training. According to surgeons, decisions were significantly more often made
      together with the patient after training (before, 38.9% vs after, 73.7%, p=0.04).
      Sub-analyses per diagnosis showed that patient experiences among older PC
      patients consistent and clinically relevant changed in the direction of improved
      decision-making after training (SDM-Q-9 +13.4 [95% CI -7.9; 34.6], VAS-I +0.27
      [95% CI -1.1; 1.6], VAS-S +0.88 [95% CI -0.5; 2.2], DRS -10.3 [95% CI -27.8;
      7.1]). Conclusion: This pilot study strengthens the practical potential of the
      intervention's concept among older surgical cancer patients.

PMID- 29184445
TI  - The relation of CUN-BAE index and BMI with body fat, cardiovascular events and
      diabetes during a 6-year follow-up: the Hordaland Health Study.
AB  - Objective: We compared Clinica Universidad de Navarra-Body Adiposity Estimator
      (CUN-BAE) and body mass index (BMI) as correlates of body fat percent (BF%) and
      the association with future risk of cardiovascular disease (CVD) and type 2
      diabetes in a Caucasian population. Methods: We used data from 6796 individuals
      (born 1925-27 and 1950-52) from the Hordaland Health Study, a prospective cohort
      study in Norway. The study was conducted in 1992-1993 and 1997-1999. Cross
      sectional analyses were conducted with data from 1997/99, including BF% measured
      by dual-energy X-ray absorptiometry. Longitudinal analyses included BMI and CUN
      BAE calculated in 1992/93, and self-reported information on CVD events and
      diabetes in 1997/99. Results: The correlation between CUN-BAE and BF% (r=0.88)
      was stronger than between BMI and BF% (r=0.56). In sex-stratified analyses, CUN
      BAE and BMI correlated similarly with BF% in men (r=0.77 and r=0.76,
      respectively) and women (r=0.82 and r=0.81, respectively). In longitudinal
      analyses, the odds ratio (per 1 SD increase) of CVD and type 2 diabetes was
      higher for BMI (ORCVD =1.23 [95% CI: 1.11-1.36]; ORdiabetes =2.11 [1.82-2.45])
      than for CUN-BAE (ORCVD =1.15 [1.04-1.27]; ORdiabetes =2.06 [1.72-2.47]) in the
      total population. In sex-stratified analyses, CUN-BAE showed higher CVD and
      diabetes risk than BMI: in men BMI ORCVD =1.22 (1.04-1.44), ORdiabetes =2.13
      (1.64-2.83); CUN-BAE ORCVD =1.93 (1.54-2.43), ORdiabetes =4.33 (2.80-6.71); and
      in women BMI ORCVD =1.22 (1.07-1.39), ORdiabetes =2.11 (1.76-2.53); CUN-BAE ORCVD
      =2.06 (1.69-2.51), ORdiabetes =5.45 (3.87-7.67). Conclusion: CUN-BAE is more
      strongly associated with future risk of type 2 diabetes and CVD compared with BMI
      in analysis stratified by sex. As a measure of adiposity in men and women
      separately, CUN-BAE has no advantage over BMI, except when the value of estimated
      BF% itself is of interest.

PMID- 29184444
TI  - Development and validation of a panel of five proteins as blood biomarkers for
      early detection of colorectal cancer.
AB  - Objective: Reliable noninvasive biomarkers for early detection of colorectal
      cancer (CRC) are highly desirable for efficient population-based screening with
      high adherence rates. We aimed to discover and validate blood-based protein
      markers for the early detection of CRC. Patients and methods: A two-stage design
      with a discovery and a validation set was used. In the discovery phase, plasma
      levels of 92 protein markers and serum levels of TP53 autoantibody were measured
      in 226 clinically recruited CRC patients and 118 controls who were free of
      colorectal neoplasms at screening colonoscopy. An algorithm predicting the
      presence of CRC was derived by Lasso regression and validated in a validation set
      consisting of all available 41 patients with CRC and a representative sample of
      106 participants with advanced adenomas and 107 controls free of neoplasm from a
      large screening colonoscopy cohort (N=6018). Receiver operating characteristic
      (ROC) analyses were conducted to evaluate the diagnostic performance of
      individual biomarkers and biomarker combinations. Results: An algorithm based on
      growth differentiation factor 15 (GDF-15), amphiregulin (AREG), Fas antigen
      ligand (FasL), Fms-related tyrosine kinase 3 ligand (Flt3L) and TP53 autoantibody
      was constructed. In the validation set, the areas under the curves of this five
      marker algorithm were 0.82 (95% CI, 0.74-0.90) for detecting CRC and 0.60 (95%
      CI, 0.52-0.69) for detecting advanced adenomas. At cutoffs yielding 90%
      specificity, the sensitivities (95% CI) for detecting CRC and advanced adenomas
      were 56.4% (38.4%-71.8%) and 22.0% (13.4%-35.4%), respectively. The five-marker
      panel showed similar diagnostic efficacy for the detection of early- and late
      stage CRC. Conclusion: The identified most promising biomarkers could contribute
      to the development of powerful blood-based tests for CRC screening in the future.

PMID- 29184446
TI  - Birth weight, sex, and celiac disease: a nationwide twin study.
AB  - Objective: Earlier research suggests that birth weight may be associated with
      celiac disease (CD), but the direction of association has been unclear
      potentially due to confounding effect from genetic and intrafamilial factors.
      Through within-twin analyses, we aimed to minimize confounding effects such as
      twins that share genetic and early environmental exposures. Materials and
      methods: Using the Swedish Twin Registry, we examined the birth weight of 146,830
      twins according to the CD status. CD was defined as having villous atrophy
      according to a small intestinal biopsy reports. Results: The prevalence of
      diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD-non-CD
      twins. Comparing the 669 CD patients with non-CD twins, the association between
      birth weight and future CD was not statistically significant (odds ratio [OR] per
      1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97-1.38).
      In males, the association was positive and statistically significant (OR=1.50;
      95% CI=1.11-2.02). However, the association was not significant in within-pair
      analyses for both dizygotic and monozygotic twins and for both sexes. Conclusion:
      This population-based study found that in male twins, higher birth weight was
      associated with higher risk of CD. However, when comparing discordant twin pairs
      in within-twin pair analyses, there was no statistically significant association
      between birth weight, intrauterine growth, and future risk of CD.

PMID- 29184447
TI  - Aseptic-avascular osteonecrosis: local "silent inflammation" in the jawbone and
      RANTES/CCL5 overexpression.
AB  - Of the definitions listed in the International Statistical Classification of
      Diseases and Related Health Problems, tenth revision (ICD-10), two disease
      descriptions can be found together: "idiopathic aseptic bone necrosis" and
      "avascular bone necrosis." The relevant literature on both the conditions
      abbreviates both as "aseptic ischemic osteonecrosis in the jawbone" (AIOJ). To
      shed light on the clinical details of this condition, osteolytic jawbone samples
      of 24 patients with different systemic immunological diseases were examined using
      four steps: presurgical dental X-ray, postsurgical histology, polymerase chain
      reaction DNA analysis (PCR DNA) of bacteria, and RANTES/CCL5 (R/C) expression.
      These four steps showed that neither X-ray nor histology delivered unambiguous
      results with respect to inflammatory processes; furthermore, the PCR results did
      not show evidence of any microbial load within the jaw samples. However, there is
      a striking, coherent overexpression of chemokine R/C in the AIOJ samples. This
      study proved the aseptic existence of "silent inflammation" within the jawbone.
      The ICD-10 (AIOJ) definition, which is hard to interpret, can now be
      substantiated with clinical evidence, while the cytokine expressions described in
      this report can explain the systemic immunological effects observed within the
      group of examined patients.

PMID- 29184448
TI  - Older adults and high-risk medication administration in the emergency department.
AB  - Background: Older adults are susceptible to adverse effects from opioids,
      nonsteroidal anti-inflammatory drugs (NSAIDs), and benzodiazepines (BZDs). We
      investigated factors associated with the administration of elevated doses of
      these medications of interest to older adults (>=65 years old) in the emergency
      department (ED). Patients and methods: ED records were queried for the
      administration of medications of interest to older adults at two academic medical
      center EDs over a 6-month period. Frequency of recommended versus elevated ("High
      doses" were defined as doses that ranged between 1.5 and 3 times higher than the
      recommended starting doses; "very high doses" were defined as higher than high
      doses) starting doses of medications, as determined by geriatric
      pharmacy/medicine guidelines and expert consensus, was compared by age groups (65
      69, 70-74, 75-79, 80-84, and >=85 years), gender, and hospital. Results: There
      were 17896 visits representing 11374 unique patients >65 years of age (55.3% men,
      44.7% women). A total of 3394 doses of medications of interest including 1678
      high doses and 684 very high doses were administered to 1364 different patients.
      Administration of elevated doses of medications was more common than that of
      recommended doses. Focusing on opioids and BZDs, the 65-69-year age group was
      much more likely to receive very high doses (1481 and 412 doses, respectively)
      than the >=85-year age groups (relative risk [RR] 5.52, 95% CI 2.56-11.90),
      mainly reflecting elevated opioid dosing (RR 8.28, 95% CI 3.69-18.57). Men were
      more likely than women to receive very high doses (RR 1.47, 95% CI 1.26-1.72),
      primarily due to BZDs (RR 2.12, 95% CI 2.07-2.16). Conclusion: Administration of
      elevated doses of opioids and BZDs in the older population occurs frequently in
      the ED, especially to the 65-69-year age group and men. Further attention to
      potentially unsafe dosing of high-risk medications to older adults in the ED is
      warranted.

PMID- 29184450
TI  - Coexisting multiple myeloma, lymphoma, and non-small cell lung cancer: a case
      report and review of the literature.
AB  - Multiple myeloma is a plasma cell dyscrasia characterized by neoplastic
      proliferation of plasma cells, producing a monoclonal immunoglobulin. Small
      lymphocytic lymphoma (SLL) is a neoplasm consisting of monoclonal B-cell
      lymphocyte proliferation. We present an extremely rare case of coexisting
      multiple myeloma, SLL, and squamous cell carcinoma of the lung in a 74-year-old
      female patient. She initially presented with a midline mass with pain in the
      lumbar area. Debulking surgery was performed, and pathology showed plasmacytoma.
      Further evaluation revealed coexistent IgG kappa myeloma. Imaging revealed
      extensive abdominal lymphadenopathy, and mesenteric lymph node biopsy confirmed
      the presence of SLL. The patient was also found to have a mass in the left lower
      lobe of the lung; biopsy showed squamous cell carcinoma. This patient was treated
      with lenalidomide and dexamethasone for multiple myeloma, and stereotactic body
      radiotherapy for limited stage lung cancer. Due to the more indolent course of
      SLL, watchful waiting was applied.

PMID- 29184451
TI  - Population pharmacokinetics of pomalidomide in patients with relapsed or
      refractory multiple myeloma with various degrees of impaired renal function.
AB  - Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory
      multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To
      assess the impact of renal impairment on pomalidomide exposure, a population
      pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various
      degrees of impaired renal function was developed. Intensive and sparse
      pomalidomide concentration data collected from two clinical studies in rrMM
      patients with normal renal function, moderately impaired renal function, severely
      impaired renal function not requiring dialysis, and with severely impaired renal
      function requiring dialysis were pooled over the dose range of 2 to 4 mg, to
      assess specifically the influence of the impaired renal function as a categorical
      variable and a continuous variable on pomalidomide clearance and plasma exposure.
      In addition, pomalidomide concentration data collected on dialysis days from both
      the withdrawal (arterial) side and from the returning (venous) side of the
      dialyzer, from rrMM patients with severely impaired renal function requiring
      dialysis, were used to assess the extent to which dialysis contributes to the
      removal of pomalidomide from blood circulation. PPK analyses demonstrated that
      moderate to severe renal impairment not requiring dialysis has no influence on
      pomalidomide clearance or plasma exposure, as compared to those patients with
      normal renal function, while pomalidomide exposure increased approximately 35% in
      patients with severe renal impairment requiring dialysis on nondialysis days. In
      addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12
      L/h, indicating that dialysis will significantly remove pomalidomide from the
      blood circulation. Thus, pomalidomide should be administered post-dialysis on the
      days of dialysis.

PMID- 29184449
TI  - Diabetes, metabolic syndrome and dyslipidemia in people living with HIV in
      Africa: re-emerging challenges not to be forgotten.
AB  - Background: The current challenge in managing people living with human
      immunodeficiency virus (PLWHIV) includes the identification and monitoring for
      comorbid health risks associated with HIV and its treatment and longer survival.
      Dyslipidemia, diabetes mellitus and metabolic syndrome are increasingly seen in
      PLWHIV. Objective: In this narrative review, we aimed to summarize the current
      knowledge about diabetes, dyslipidemia and metabolic syndrome in PLWHIV in Africa
      and also to discuss the challenges that patients as well as health authorities in
      Africa may face. Methods: PubMed and Google scholar published-English literatures
      concerning earlier mentioned entities regardless of time limit were critically
      reviewed. Results: The prevalence of metabolic disorders in HIV population in
      Africa was estimated to range from 2.1% to 26.5% for diabetes and 20.2% to 43.5%
      for pre-diabetes, 13% to 58% for metabolic syndrome and 13% to 70% for
      dyslipidemia. Conclusion: The management of metabolic disorders and
      cardiovascular disease risks related to HIV is complex especially in Africa due
      to healthcare resources, but our experience suggests that metabolic clinic is
      beneficial to patients and staff and should be an important part of HIV services
      especially as the older HIV population is increasing. In this context,
      cardiovascular risk assessment of HIV-infected patients will become an important
      component of care in developing countries in Africa and strategies are needed to
      deal with progressive increase in the epidemic of type 2 diabetes, dyslipidemia
      and metabolic syndrome.

PMID- 29184452
TI  - Violence toward health workers in Bahrain Defense Force Royal Medical Services'
      emergency department.
AB  - Background: Employees working in emergency departments (EDs) in hospital settings
      are disproportionately affected by workplace violence as compared to those
      working in other departments. Such violence results in minor or major injury to
      these workers. In other cases, it leads to physical disability, reduced job
      performance, and eventually a nonconducive working environment for these workers.
      Materials and methods: A cross-sectional exploratory questionnaire was used to
      collect data used for the examination of the incidents of violence in the
      workplace. This study was carried out at the ED of the Bahrain Defense Force
      (BDF) Hospital. Participants for the study were drawn from nurses, support staff,
      and emergency physicians. Both male and female workers were surveyed. Results:
      The study included responses from 100 staff in the ED of the BDF Hospital in
      Bahrain (doctors, nurses, and support personnel). The most experienced type of
      violence in the workers in the past 12 months in this study was verbal abuse,
      which was experienced by 78% of the participants, which was followed by physical
      abuse (11%) and then sexual abuse (3%). Many cases of violence against ED workers
      occurred during night shifts (53%), while physical abuse was reported to occur
      during all the shifts; 40% of the staff in the ED of the hospital were not aware
      of the policies against workplace violence, and 26% of the staff considered
      leaving their jobs at the hospital. Conclusion: This study reported multiple
      findings on the number of workplace violence incidents, as well as the
      characteristics and factors associated with violence exposure in ED staff in
      Bahrain. The results clearly demonstrate the importance of addressing the issue
      of workplace violence in EDs in Bahrain and can be used to demonstrate the strong
      need for interventions.

PMID- 29184453
TI  - Physical activity and sedentary behavior in patients with systemic lupus
      erythematosus and rheumatoid arthritis.
AB  - Objective: Patients with systemic lupus erythematosus (SLE) and rheumatoid
      arthritis (RA) are at increased risk of cardiovascular disease (CVD). As
      sedentary behavior and lack of physical activity are known cardiovascular risk
      factors, we compared habitual activity between SLE patients, RA patients, and
      healthy control participants. Patients and methods: For this cross-sectional
      study, RA and SLE patients were recruited from rheumatology clinics at an
      academic medical center from April 2013 to December 2014. Healthy control
      participants were recruited through local advertising during the same time
      period. Habitual activity was measured using a triaxial accelerometer worn during
      waking hours for 7 consecutive days. Minutes per day of sedentary, light, and
      moderate-vigorous physical activity (MVPA) were recorded and compared between
      SLE, RA, and healthy participants using ANOVA. Results: There were 59
      participants included in the analysis: 20 SLE patients, 19 RA patients, and 20
      healthy controls. Disease activity was quiescent in both the SLE and RA groups.
      All three groups demonstrated high sedentary behavior (mean +/- SD sedentary time
      for all participants: 10.1+/-1.3 hours/day; 76.4% total wear time). There were no
      significant differences between SLE, RA, and healthy participants in time spent
      in sedentary behavior (p=0.80) or light activity (p=0.17). Total MVPA (mean +/-
      SD, minutes/day) was significantly lower in SLE (34.5+/-22.7; p<0.001) and RA
      (41.5+/-21.3; p=0.005) patients compared to controls (64.9+/-22.4). Conclusion:
      SLE and RA patients demonstrate suboptimal MVPA despite well-controlled disease.
      Given their increased CVD risk, effective interventions are required to improve
      habitual physical activity levels in both populations.

PMID- 29184454
TI  - Sleep quality and circadian rhythm disruption in the intensive care unit: a
      review.
AB  - Sleep and circadian rhythm are reported to be severely abnormal in critically ill
      patients. Disturbed sleep can lead to the development of delirium and, as a
      result, can be associated with prolonged stay in the intensive care unit (ICU)
      and increased mortality. The standard criterion method of sleep assessment,
      polysomnography (PSG), is complicated in critically ill patients due to the
      practical challenges and interpretation difficulties. Several PSG sleep studies
      in the ICU reported the absence of normal sleep characteristics in many
      critically ill patients, making the standard method of sleep scoring insufficient
      in this patient group. Watson et al proposed a modified classification for sleep
      scoring in critically ill patients. This classification has not yet been
      validated. Sleep disturbance in the ICU is a multifactorial problem. The ICU
      environment, mechanical ventilation, medication, as well as the critical illness
      itself have been reported as important sleep disturbing factors. Secretion of
      sleep hormone, melatonin, expressing circadian rhythmicity was found abolished or
      phase delayed in critically ill patients. Various interventions have been tested
      in several studies aiming to improve sleep quality and circadian rhythm in the
      ICU. The results of these studies were inconclusive due to using the sleep
      assessment methods other than PSG or the absence of a reliable sleep scoring tool
      for the analysis of the PSG findings in this patient population. Development of a
      valid sleep scoring classification is essential for further sleep research in
      critically ill patients.

PMID- 29184455
TI  - Using PROMs to guide patients and practitioners through the head and neck cancer
      journey.
AB  - The measurement of patient-reported outcome measures (PROMs) following head and
      neck cancer (HNC) has the capacity to substantially enhance the care of patients
      and their care-givers following the diagnosis and treatment of HNC. Literature
      concerning PROMs has increased exponentially in the past 2 decades, producing a
      vast array of data upon which the multidisciplinary team can reflect. For this
      review, "Handle On QOL" has been used as a source of references to illustrate the
      points raised. PROMs are contextualized by considering the clinically-distinct
      key stages that cancer patients endure: diagnosis, treatment, acute toxicity,
      early recovery, late effects, recurrence, and palliation. The PROMs are
      considered in six main categories: 1) those addressing cornucopia of issues not
      specific to cancer; 2) those addressing issues common to all cancers; 3)
      questionnaires with items specific to HNC; 4) questionnaires that focus on a
      particular aspect of head and neck function; 5) those measuring psychological
      concerns, such as depression, anxiety, or self-esteem; and 6) item prompt lists.
      Potential benefits of PROMs in clinical practice are discussed, as are barriers
      to use. The way forward in integrating PROMs into routine HNC care is discussed
      with an emphasis on information technology.

PMID- 29184456
TI  - Validating the Patient Experience with Treatment and Self-Management (PETS), a
      patient-reported measure of treatment burden, in people with diabetes.
AB  - Aims: To validate a comprehensive general measure of treatment burden, the
      Patient Experience with Treatment and Self-Management (PETS), in people with
      diabetes. Methods: We conducted a secondary analysis of a cross-sectional survey
      study with 120 people diagnosed with type 1 or type 2 diabetes and at least one
      additional chronic illness. Surveys included established patient-reported outcome
      measures and a 48-item version of the PETS, a new measure comprised of multi-item
      scales assessing the burden of chronic illness treatment and self-care as it
      relates to nine domains: medical information, medications, medical appointments,
      monitoring health, interpersonal challenges, health care expenses, difficulty
      with health care services, role activity limitations, and physical/mental
      exhaustion from self-management. Internal reliability of PETS scales was
      determined using Cronbach's alpha. Construct validity was determined through
      correlation of PETS scores with established measures (measures of chronic
      condition distress, medication satisfaction, self-efficacy, and global well
      being), and known-groups validity through comparisons of PETS scores across
      clinically distinct groups. In an exploratory test of predictive validity, step
      wise regressions were used to determine which PETS scales were most associated
      with outcomes of chronic condition distress, overall physical and mental health,
      and medication adherence. Results: Respondents were 37-88 years old, 59% female,
      29% non-white, and 67% college-educated. PETS scales showed good reliability
      (Cronbach's alphas >=0.74). Higher PETS scale scores (greater treatment burden)
      were correlated with more chronic condition distress, less medication
      convenience, lower self-efficacy, and worse general physical and mental health.
      Participants less (versus more) adherent to medications and those with more
      (versus fewer) health care financial difficulties had higher mean PETS scores.
      Medication burden was the scale that was most consistently associated with well
      being and patient-reported adherence. Conclusion: The PETS is a reliable and
      valid measure for assessing perceived treatment burden in people coping with
      diabetes.

PMID- 29184457
TI  - Evaluation of EU legislation on blood: a bioethical point of view.
AB  - A review of the European Union (EU) regulations concerning blood, tissues, and
      cells of human origin is under way in the EU. From the ethical point of view, the
      non-remuneration of donations and the ban on deriving gain from human biological
      materials are of particular significance. While the basic ethical principles
      involved in the procurement, preservation, and use of these materials are the
      same, their practical application should be adapted to the specific context of
      each material. In the case of donation and use of blood, in particular, the issue
      of legitimate reimbursements to donors and for transfusion centers has to be
      managed in accordance with the principle of non-commercialization. There is also
      a need for strict rules to avoid possible commercial spillover effects from blood
      derived products. The author proposes ethical criteria regarding reimbursements
      to donors, costs associated with processing, and the development (and possible
      marketing) of products.

PMID- 29184460
TI  - Understanding of evaluation capacity building in practice: a case study of a
      national medical education organization.
AB  - Introduction: Evaluation capacity building (ECB) is a topic of great interest to
      many organizations as they face increasing demands for accountability and
      evidence-based practices. ECB is about building the knowledge, skills, and
      attitudes of organizational members, the sustainability of rigorous evaluative
      practices, and providing the resources and motivations to engage in ongoing
      evaluative work. There exists a solid foundation of theoretical research on ECB,
      however, understanding what ECB looks like in practice is relatively thin. Our
      purpose was to investigate what ECB looks like firsthand within a national
      medical educational organization. Methods: The context for this study was the
      Acute Critical Events Simulation (ACES) organization in Canada, which has
      successfully evolved into a national educational program, driven by physicians.
      We conducted an exploratory qualitative study to better understand and describe
      ECB in practice. In doing so, interviews were conducted with program leaders and
      instructors so as to gain a richer understanding of evaluative processes and
      practices. Results: A total of 21 individuals participated in the semistructured
      interviews. Themes from our qualitative data analysis included the following:
      evaluation knowledge, skills, and attitudes, use of evaluation findings, shared
      evaluation beliefs and commitment, evaluation frameworks and processes, and
      resources dedicated to evaluation. Conclusion: The national ACES organization was
      a useful case study to explore ECB in practice. The ECB literature provided a
      solid foundation to understand the purpose and nuances of ECB. This study added
      to the paucity of studies focused on examining ECB in practice. The most
      important lesson learned was that the organization must have leadership who are
      intrinsically motivated to employ and use evaluation data to drive ongoing
      improvements within the organization. Leaders who are intrinsically motivated
      will employ risk taking when evaluation practices and processes may be somewhat
      unfamiliar. Creating and maintaining a culture of data use and ongoing inquiry
      have enabled national ACES to achieve a sustainable evaluation practice.

PMID- 29184459
TI  - Simulation in bronchoscopy: current and future perspectives.
AB  - Objective: To provide an overview of current literature that informs how to
      approach simulation practice of bronchoscopy and discuss how findings from other
      simulation research can help inform the use of simulation in bronchoscopy
      training. Summary: We conducted a literature search on simulation training of
      bronchoscopy and divided relevant studies in three categories: 1) structuring
      simulation training in bronchoscopy, 2) assessment of competence in bronchoscopy
      training, and 3) development of cheap alternatives for bronchoscopy simulation.
      Conclusion: Bronchoscopy simulation is effective, and the training should be
      structured as distributed practice with mastery learning criteria (ie, training
      until a certain level of competence is achieved). Dyad practice (training in
      pairs) is possible and may increase utility of available simulators. Trainee
      performance should be assessed with assessment tools with established validity.
      Three-dimensional printing is a promising new technology opening possibilities
      for developing cheap simulators with innovative features.

PMID- 29184458
TI  - Update on the management of systemic juvenile idiopathic arthritis and role of IL
      1 and IL-6 inhibition.
AB  - Systemic juvenile idiopathic arthritis (SJIA) is a disease marked with arthritis
      and several features of systemic inflammation including fevers, rashes,
      hepatosplenomegaly, lymphadenopathy, and serositis. The presentation can be
      variable and arthritis can be a later feature. Macrophage activation syndrome can
      be a life-threatening complication of this illness and requires early recognition
      and prompt therapy. Advancements in understanding the biology of SJIA have led to
      the development of cytokine-targeted therapies, mainly interleukin-1 (IL-1) and
      IL-6 inhibitors that have significantly improved outcomes. In this review, we
      provide an update on the advances in the understanding of SJIA biology and also
      the therapeutic options.

PMID- 29184462
TI  - Rodrigo Oliva Perez, MD, PhD.

PMID- 29184461
TI  - Additional factors influencing resident satisfaction and dissatisfaction.

PMID- 29184463
TI  - New Horizons in Rectal Cancer Management.

PMID- 29184464
TI  - New Horizons in Rectal Cancer Management in Colon and Rectal Surgery.

PMID- 29184465
TI  - How Should Imaging Direct/Orient Management of Rectal Cancer?
AB  - Modern rectal cancer management is dependent on preoperative staging, and
      radiological assessment is a crucial part of this process. Imaging must provide
      sufficient information to guide preoperative decision-making that is reliable and
      reproducible. Different methods have been used for local staging; however,
      magnetic resonance imaging (MRI) has shown to be the most reliable tool for this
      purpose. MRI offers prognostic information about the patients and guides the
      decision between neoadjuvant treatment and total mesorectal excision alone. Also,
      not only the initial staging but also restaging by MRI can provide significant
      information regarding tumor response that is essential when considering
      alternative approaches.

PMID- 29184467
TI  - The Perfect Total Mesorectal Excision Obviates the Need for Anything Else in the
      Management of Most Rectal Cancers.
AB  - This article discusses the local control of primary rectal cancer and its
      locoregional spread in the light of modern advances. In recent years, the use of
      neoadjuvant chemoradiation has spread widely. However, its true benefit is not
      always balanced with its morbidities. Often total mesorectal excision (TME) is
      the best option. We will discuss the indications for immediate surgery for
      chemoradiation in advance and the importance of a delay in the management plan.
      To understand this selection, it is mandatory to know the true extent of tissue
      at risk for tumor dissemination and spread. Considering that TME may be enough
      for many patients and that most local recurrences are failures of surgical
      technique we introduce a new concept of total mesorectal irradiation. This
      exploits the new reality that precise, focused neoadjuvant therapy can offer a
      better response with fewer complications. Together these important changes in
      cancer board (multidisciplinary team) planning can also offer selected patients
      complete control of their cancer with no need for surgery.

PMID- 29184466
TI  - Local Excision and Endoscopic Resections for Early Rectal Cancer.
AB  - Radical surgery is considered as the standard treatment for rectal cancer.
      Transanal local excision has been considered an interesting alternative for the
      management of selected patients with rectal cancers for many decades. Different
      approaches had been considered for local excision, from endoscopic submucosal
      dissection to resections using platforms, such as transanal endoscopic
      microsurgery or transanal minimally invasive surgery. Identifying the ideal
      candidate for this approach is crucial, as a local failure after local excision
      is associated with poor outcomes, even for an initial early rectal tumor. In this
      article, the diagnostic tools and criteria to select patients for local excision,
      the different modalities used, and the outcomes are discussed.

PMID- 29184468
TI  - Is There Any Reason Not to Perform Standard Laparoscopic Total Mesorectal
      Excision?
AB  - The curative treatment of locally advanced rectal cancer is currently based on
      chemoradiotherapy and total mesorectal excision (TME). Laparoscopy has developed
      considerably because of obvious clinical benefits such as reduced pain and
      shorter hospital stay. Recently, several prospective randomized clinical trials
      with long-term follow-up have showed that laparoscopy is noninferior to
      laparotomy with the same oncologic outcomes in terms of survival and local
      control rate. However, laparoscopic TME remains a challenging procedure requiring
      a high level of expertise and a long learning curve to ensure an adequate and
      safe resection. The only relative contraindication of laparoscopic rectal surgery
      is T4 rectal cancer extended beyond the plane of TME. In this situation, it is
      reasonable to consider an open resection to avoid an uncomplete resection. In
      obese and elderly patients, laparoscopic TME also provides the same benefits as
      in nonobese and younger patients but may be more difficult to achieve. This
      review summarizes current knowledge on the place of laparoscopic TME in the
      treatment of rectal cancer.

PMID- 29184469
TI  - Transanal Total Mesorectal Excision: Why, When, and How.
AB  - Transanal total mesorectal excision (taTME) has evolved over the past decade
      fueled by advances in minimally invasive surgery. The technique aims to overcome
      the constraints posed by a narrow rigid pelvis and poor TME visualization that
      are encountered during "top-down" rectal surgery. A more accurate pelvic
      dissection should subsequently result in safer oncological resections and better
      preservation of pelvic autonomic nerves. taTME is an advanced complex technique
      that requires dedicated training and experience in TME surgery. Initial results
      from small cohorts are promising and confirmation by randomized controlled trials
      is eagerly awaited.

PMID- 29184470
TI  - Is There Any Reason to Still Consider Lateral Lymph Node Dissection in Rectal
      Cancer? Rationale and Technique.
AB  - Nodal dissemination in locally advanced rectal cancer occurs mainly in two
      directions: upward and lateral. Lateral node involvement has been demonstrated;
      however, lateral lymph node dissection (LLND) is not routinely performed in
      Western countries and the focus is more on neoadjuvant treatment regimens. The
      main reasons for this are the high morbidity associated with the operation and
      the uncertain oncological benefit. There is, however, recent evidence that in
      selected cases, neoadjuvant treatment combined with total mesorectal excision
      only might not be sufficient. In this article, the historical developments in the
      East and the West, the current evidence regarding lateral nodal disease, and the
      surgical steps in the LLND are discussed.

PMID- 29184471
TI  - Abdominoperineal Excision: Technical Challenges in Optimal Surgical and
      Oncological Outcomes after Abdominoperineal Excision for Rectal Cancer.
AB  - Treatment results in rectal cancer have improved significantly during the recent
      two decades, but local control and survival after abdominoperineal excision (APE)
      have not improved to the same degree as that seen after anterior resection (AR).
      The reason for this is an increased risk of inadvertent bowel perforations and
      tumor involved margins after APE as compared with AR. The conventional
      synchronous combined APE has not been a standardized procedure and consequently
      oncological outcomes have varied considerably between different institutions and
      in different reports. With the new concept of APE, based on well-defined
      anatomical structures, the procedure can be categorized as intersphincteric APE,
      extralevator APE, and ischioanal APE. This article discusses the technical
      aspects and results from this approach.

PMID- 29184472
TI  - Intersphincteric Resection Pushing the Envelope for Sphincter Preservation.
AB  - During the last 15 years, a significant evolution has emerged in the surgical
      treatment of rectal cancer and restoration of bowel continuity has been one of
      the main goals. For many years the treatment of distal rectal cancer would
      necessarily require an abdominoperineal resection and end colostomy. The surgical
      procedure of intersphincteric resection has been proposed to offer sphincter
      preservation in patients with low rectal cancer and has been legitimized if
      executed according to adequate oncologic criteria. This article will discuss the
      best indications, technical aspects, functional, and oncological outcomes of
      intersphicteric resection in the management of rectal cancer.

PMID- 29184473
TI  - Neoadjuvant Treatment Strategies: Advanced Radiation Alternatives.
AB  - Long-course chemoradiation therapy (CRT) has been the standard approach for
      locally advanced rectal tumors. Neoadjuvant CRT is associated to improved local
      disease control, with less toxicity when compared with adjuvant CRT, as well as
      the chance for pathologic complete response. The CRT regimens have improved over
      the past years. This article will examine selected controversies, including novel
      chemoradiation regimens, duration of radiation (short vs. long course), and
      radiation techniques such as intensity-modulated radiation therapy (IMRT).

PMID- 29184474
TI  - Neoadjuvant Strategies: Locally Advanced Rectal Cancer.
AB  - Colorectal cancer is one of the major leading causes of death in both men and
      women. The successful management of colon or rectal cancer demands a
      multidisciplinary approach. In the last few years, significant improvement has
      been noticed in the management of localized rectal cancer to reduce local
      recurrence and obtain complete pathological response following appropriate
      surgical steps, if necessary. Implementation of neoadjuvant therapy not only
      enhances disease control, it may also ensure sphincter preserving procedures or
      organ-preserving options. This article principally concentrates on the current
      neoadjuvant treatment for locally advanced rectal cancer and the prognostic
      outcomes of such therapy, including a discussion on the historical perspective.

PMID- 29184475
TI  - Management of the Complete Clinical Response.
AB  - Organ preservation is considered in the management of selected patients with
      rectal cancer. Complete clinical response observed after neoadjuvant
      chemoradiation for rectal cancer is one of these cases. Patients who present
      complete clinical response are candidates to the watch-and-wait approach, when
      radical surgery is not immediately performed and is offered only to patients in
      the event of a local relapse. These patients are included in a strict follow-up,
      and up of 70% of them will never be operated during the follow-up. This strategy
      is associated with similar oncological outcomes as patients operated on, and the
      advantage of avoiding the morbidity associated to the radical operation. In this
      article we will discuss in detail the best candidates for this approach, the
      protocol itself, and the long-term outcomes.

PMID- 29184476
TI  - Organ-Preserving Strategies for the Management of Near-Complete Responses in
      Rectal Cancer after Neoadjuvant Chemoradiation.
AB  - In recent years, organ preservation has been considered a feasible alternative to
      total mesorectal excision for patients with locally advanced rectal cancer with a
      clinical complete response to neoadjuvant therapy. However, the degree of tumor
      response to neoadjuvant therapy is variable. A fraction of the patients who did
      not achieve a complete response had grossly visible tumors. These patients, with
      clearly incomplete clinical response, need a total mesorectal excision. In
      addition, some patients with a significant tumor response still have some
      abnormalities in the bowel wall, such as superficial ulceration or tissue
      nodularity, which, while not conclusive for the presence of a tumor, are
      indicative of the possibility of a residual tumor in the bowel wall or in
      mesorectal lymph nodes. The management of patients with a so-called near-complete
      clinical response to neoadjuvant therapy is controversial. In this article, we
      will review the clinical and radiological criteria that define a clinical
      response to neoadjuvant therapy, possible treatment strategies, and follow-up
      protocols. We will also discuss patient and tumor characteristics that in our
      opinion can be useful in selecting the most appropriate treatment alternative.
      Although organ preservation and quality of life are important, the primary goal
      of treatment for these patients should be local tumor control and long-term
      survival.

PMID- 29184477
TI  - Molecular Biology: Are We Getting Any Closer to Providing Clinically Useful
      Information?
AB  - Advances in molecular biology and biomarker research have significantly impacted
      our understanding and treatment of multiple solid malignancies. In rectal cancer,
      where neoadjuvant chemoradiation is widely used for locally advanced disease,
      most efforts have focused on the identification of predictors of response in an
      attempt to appropriately select patients for multimodality therapy. A variety of
      biomarkers have been studied, including genetic mutations, chromosomal copy
      number alterations, and single as well as multigene expression patterns. Also, as
      transanal resection of rectal tumors requires accurate preoperative detection of
      lymph node metastasis, the identification of biomarkers of regional nodal
      involvement has been another important field of active research. While
      preliminary results have been promising, lack of external validation means has a
      limited translation to clinical use. This review summarizes recent developments
      in rectal cancer biomarker research, highlighting the challenges associated with
      their adoption, and evaluating their potential for clinical use.

PMID- 29184479
TI  - Visual Sensory Signals Dominate Tactile Cues during Docked Feeding in
      Hummingbirds.
AB  - Animals living in and interacting with natural environments must monitor and
      respond to changing conditions and unpredictable situations. Using information
      from multiple sensory systems allows them to modify their behavior in response to
      their dynamic environment but also creates the challenge of integrating
      different, and potentially contradictory, sources of information for behavior
      control. Understanding how multiple information streams are integrated to produce
      flexible and reliable behavior is key to understanding how behavior is controlled
      in natural settings. Natural settings are rarely still, which challenges animals
      that require precise body position control, like hummingbirds, which hover while
      feeding from flowers. Tactile feedback, available only once the hummingbird is
      docked at the flower, could provide additional information to help maintain its
      position at the flower. To investigate the role of tactile information for
      hovering control during feeding, we first asked whether hummingbirds physically
      interact with a feeder once docked. We quantified physical interactions between
      docked hummingbirds and a feeder placed in front of a stationary background
      pattern. Force sensors on the feeder measured a complex time course of loading
      that reflects the wingbeat frequency and bill movement of feeding hummingbirds,
      and suggests that they sometimes push against the feeder with their bill. Next,
      we asked whether the measured tactile interactions were used by feeding
      hummingbirds to maintain position relative to the feeder. We created two
      experimental scenarios-one in which the feeder was stationary and the visual
      background moved and the other where the feeder moved laterally in front of a
      white background. When the visual background pattern moved, docked hummingbirds
      pushed significantly harder in the direction of horizontal visual motion. When
      the feeder moved, and the background was stationary, hummingbirds generated
      aerodynamic force in the opposite direction of the feeder motion. These results
      suggest that docked hummingbirds are using visual information about the
      environment to maintain body position and orientation, and not actively tracking
      the motion of the feeder. The absence of flower tracking behavior in hummingbirds
      contrasts with the behavior of hawkmoths, and provides evidence that they rely
      primarily on the visual background rather than flower-based cues while feeding.

PMID- 29184480
TI  - Low Cost Electrode Assembly for EEG Recordings in Mice.
AB  - Wireless electroencephalography (EEG) of small animal subjects typically utilizes
      miniaturized EEG devices which require a robust recording and electrode assembly
      that remains in place while also being well-tolerated by the animal so as not to
      impair the ability of the animal to perform normal living activities or
      experimental tasks. We developed simple and fast electrode assembly and method of
      electrode implantation using electrode wires and wire-wrap technology that
      provides both higher survival and success rates in obtaining recordings from the
      electrodes than methods using screws as electrodes. The new wire method results
      in a 51% improvement in the number of electrodes that successfully record EEG
      signal. Also, the electrode assembly remains affixed and provides EEG signal for
      at least a month after implantation. Screws often serve as recording electrodes,
      which require either drilling holes into the skull to insert screws or affixing
      screws to the surface of the skull with adhesive. Drilling holes large enough to
      insert screws can be invasive and damaging to brain tissue, using adhesives may
      interfere with conductance and result in a poor signal, and soldering screws to
      wire leads results in fragile connections. The methods presented in this article
      provide a robust implant that is minimally invasive and has a significantly
      higher success rate of electrode implantation. In addition, the implant remains
      affixed and produces good recordings for over a month, while using economical,
      easily obtained materials and skills readily available in most animal research
      laboratories.

PMID- 29184481
TI  - Cynefin as Reference Framework to Facilitate Insight and Decision-Making in
      Complex Contexts of Biomedical Research.
AB  - The Cynefin scheme is a concept of knowledge management, originally devised to
      support decision making in management, but more generally applicable to
      situations, in which complexity challenges the quality of insight, prediction,
      and decision. Despite the fact that life itself, and especially the brain and its
      diseases, are complex to the extent that complexity could be considered their
      cardinal feature, complex problems in biomedicine are often treated as if they
      were actually not more than the complicated sum of solvable sub-problems. Because
      of the emergent properties of complex contexts this is not correct. With a set of
      clear criteria Cynefin helps to set apart complex problems from "simple/obvious,"
      "complicated," "chaotic," and "disordered" contexts in order to avoid
      misinterpreting the relevant causality structures. The distinction comes with the
      insight, which specific kind of knowledge is possible in each of these categories
      and what are the consequences for resulting decisions and actions. From student's
      theses over the publication and grant writing process to research politics,
      misinterpretation of complexity can have problematic or even dangerous
      consequences, especially in clinical contexts. Conceptualization of problems
      within a straightforward reference language like Cynefin improves clarity and
      stringency within projects and facilitates communication and decision-making
      about them.

PMID- 29184478
TI  - Visual Prosthesis: Interfacing Stimulating Electrodes with Retinal Neurons to
      Restore Vision.
AB  - The bypassing of degenerated photoreceptors using retinal neurostimulators is
      helping the blind to recover functional vision. Researchers are investigating new
      ways to improve visual percepts elicited by these means as the vision produced by
      these early devices remain rudimentary. However, several factors are hampering
      the progression of bionic technologies: the charge injection limits of metallic
      electrodes, the mechanical mismatch between excitable tissue and the stimulating
      elements, neural and electric crosstalk, the physical size of the implanted
      devices, and the inability to selectively activate different types of retinal
      neurons. Electrochemical and mechanical limitations are being addressed by the
      application of electromaterials such as conducting polymers, carbon nanotubes and
      nanocrystalline diamonds, among other biomaterials, to electrical
      neuromodulation. In addition, the use of synthetic hydrogels and cell-laden
      biomaterials is promising better interfaces, as it opens a door to establishing
      synaptic connections between the electrode material and the excitable cells.
      Finally, new electrostimulation approaches relying on the use of high-frequency
      stimulation and field overlapping techniques are being developed to better
      replicate the neural code of the retina. All these elements combined will bring
      bionic vision beyond its present state and into the realm of a viable, mainstream
      therapy for vision loss.

PMID- 29184482
TI  - Identification of Candidate Allosteric Modulators of the M1 Muscarinic
      Acetylcholine Receptor Which May Improve Vagus Nerve Stimulation in Chronic
      Tinnitus.
AB  - Chronic tinnitus is characterized by neuroplastic changes of the auditory cortex.
      A promising method for therapy of chronic tinnitus is vagus nerve stimulation
      (VNS) combined with auditory stimulation. The principle of VNS is reversal of
      pathological neuroplastic changes of the auditory cortex toward physiological
      neural activity and synchronicity. The VNS mechanism of action in chronic
      tinnitus patients is prevailingly through the muscarinic neuromodulation of the
      auditory cortex by the activation of nc. basalis Meynerti. The aim of this study
      is to propose potential pharmaceutics which may improve the neuromodulatory
      effects of VNS. The working hypothesis is that M1 receptors have a dominant role
      in the neural plasticity of the auditory cortex. We propose that allosteric
      agonists of the muscarinic receptor type 1 (M1) receptor could improve
      specificity and selectivity of the neuromodulatory effect of VNS on the auditory
      cortex of chronic tinnitus patients even in the circumstances of lower
      acetylcholine brain concentration. This intervention would also reinforce the re
      learning process of tinnitus (sub)networks by acting on cholinergic memory and
      learning mechanisms. We performed in silico screening of drug space using the
      EIIP/AQVN filter and selected 50 drugs as candidates for allosteric modulators of
      muscarinic receptors. Further filtering of these compounds by means of 3D QSAR
      and docking revealed 3 approved drugs-bromazepam, estazolam and flumazenil as the
      most promising candidates for combined chronic tinnitus therapy. These drugs
      should be further evaluated by biological tests and clinical trials.

PMID- 29184483
TI  - H3K9ac and HDAC2 Activity Are Involved in the Expression of Monocarboxylate
      Transporter 1 in Oligodendrocyte.
AB  - Recently, it is reported that monocarboxylate transporter 1 (MCT1) plays crucial
      role in oligodendrocyte differentiation and myelination. We found that MCT1 is
      strongly expressed in oligodendrocyte but weakly expressed in oligodendrocyte
      precursors (OPCs), and the underlying mechanisms remain elusive. Histone
      deacetylases (HDACs) activity is required for induction of oligodendrocyte
      differentiation and maturation. We asked whether HDACs are involved in the
      regulation of MCT1 expression. This work revealed that the acetylation level of
      histone H3K9 (H3K9ac) was much higher in mct1 gene (Slc16a1) promoter in OPCs
      than that in oligodendrocyte. H3K9ac regulates MCT1 expression was confirmed by
      HDAC acetyltransferase inhibitors trichostatin A and curcumin. Of note, there was
      a negative correlation between H3K9ac and MCT1 expression in oligodendrocyte.
      Further, we found that the levels of HDAC1, 2, and 3 protein in oligodendrocyte
      were obviously higher than those in OPCs. However, specific knockdown of HDAC2
      but not HDAC1 and HDAC3 significantly decreased the expression of MCT1 in
      oligodendrocyte. Conversely, overexpression of HDAC2 remarkably enhanced the
      expression of MCT1. The results imply that HDAC2 is involved in H3K9ac
      modification which regulates the expression of MCT1 during the development of
      oligodendrocyte.

PMID- 29184485
TI  - Globular Adiponectin Limits Microglia Pro-Inflammatory Phenotype through an
      AdipoR1/NF-kappaB Signaling Pathway.
AB  - We recently reported that increased levels of Adiponectin (ApN) in the brain led
      to microglia phenotype and activation state regulation, thus reducing both global
      brain inflammation and depressive-like behaviors in mice. Apart from this, little
      is known on ApN molecular effects on microglia, although these cells are crucial
      in both physiological and pathological processes. Here we fill this gap by
      studying the effects and targets of ApN toward neuroinflammation. Our findings
      suggest that ApN deficiency in mice leads to a higher sensitivity of mice to
      neuroinflammation that is due to enhanced microglia responsiveness to a pro
      inflammatory challenge. Moreover, we show that globular ApN (gApN) exerts direct
      in vivo anti-inflammatory actions on microglia by reducing IL-1beta, IL-6, and
      TNFalpha synthesis. In vitro, gApN anti-inflammatory properties are confirmed in
      brain-sorted microglia, primary cultured and microglia cell line (BV2), but are
      not observed on astrocytes. Our results also show that gApN blocks LPS-induced
      nitrosative and oxidative stress in microglia. Finally, we demonstrate for the
      first time that these anti-inflammatory and anti-oxidant actions of gApN on
      microglia are mediated through an AdipoR1/NF-kappaB signaling pathway.

PMID- 29184486
TI  - Differential Postnatal Expression of Neuronal Maturation Markers in the Dentate
      Gyrus of Mice and Rats.
AB  - The dentate gyrus (DG) is a unique structure of the hippocampus that is
      distinguished by ongoing neurogenesis throughout the lifetime of an organism. The
      development of the DG, which begins during late gestation and continues during
      the postnatal period, comprises the structural formation of the DG as well as the
      establishment of the adult neurogenic niche in the subgranular zone (SGZ). We
      investigated the time course of postnatal maturation of the DG in male C57BL/6J
      mice and male Sprague-Dawley rats based on the distribution patterns of the
      immature neuronal marker doublecortin (DCX) and a marker for mature neurons,
      calbindin (CB). Our findings demonstrate that the postnatal DG is marked by a
      substantial maturation with a high number of DCX-positive granule cells (GCs)
      during the first two postnatal weeks followed by a progression toward more mature
      patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks.
      The most substantial shift in maturation of the GC population took place between
      P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became
      confined to the innermost part of the GC layer (GCL), indicative of the formation
      of the SGZ. These results suggest that the first month of postnatal development
      represents an important transition phase during which DG neurogenesis and the
      maturation course of the GC population becomes analogous to the process of adult
      neurogenesis. Therefore, the postnatal DG could serve as an attractive model for
      studying a growing and functionally maturing neural network. Direct comparisons
      between mice and rats revealed that the transition from immature DCX-positive to
      mature CB-positive GCs occurs more rapidly in the rat by approximately 4-6 days.
      The remarkable species difference in the speed of maturation on the GC population
      level may have important implications for developmental and neurogenesis research
      in different rodent species and strains.

PMID- 29184484
TI  - Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?
AB  - The ketogenic diet's (KD) anticonvulsant effects have been well-documented for
      nearly a century, including in randomized controlled trials. Some patients become
      seizure-free and some remain so after diet cessation. Many recent studies have
      explored its expanded therapeutic potential in diverse neurological disorders,
      yet no mechanism(s) of action have been established. The diet's high fat, low
      carbohydrate composition reduces glucose utilization and promotes the production
      of ketone bodies. Ketone bodies are a more efficient energy source than glucose
      and improve mitochondrial function and biogenesis. Cellular energy production
      depends on the metabolic coenzyme nicotinamide adenine dinucleotide (NAD), a
      marker for mitochondrial and cellular health. Furthermore, NAD activates
      downstream signaling pathways (such as the sirtuin enzymes) associated with major
      benefits such as longevity and reduced inflammation; thus, increasing NAD is a
      coveted therapeutic endpoint. Based on differential NAD+ utilization during
      glucose- vs. ketone body-based acetyl-CoA generation for entry into the
      tricarboxylic cycle, we propose that a KD will increase the NAD+/NADH ratio. When
      rats were fed ad libitum KD, significant increases in hippocampal NAD+/NADH ratio
      and blood ketone bodies were detected already at 2 days and remained elevated at
      3 weeks, indicating an early and persistent metabolic shift. Based on diverse
      published literature and these initial data we suggest that increased NAD during
      ketolytic metabolism may be a primary mechanism behind the beneficial effects of
      this metabolic therapy in a variety of brain disorders and in promoting health
      and longevity.

PMID- 29184487
TI  - The Role of Celestial Compass Information in Cataglyphis Ants during Learning
      Walks and for Neuroplasticity in the Central Complex and Mushroom Bodies.
AB  - Central place foragers are faced with the challenge to learn the position of
      their nest entrance in its surroundings, in order to find their way back home
      every time they go out to search for food. To acquire navigational information at
      the beginning of their foraging career, Cataglyphis noda performs learning walks
      during the transition from interior worker to forager. These small loops around
      the nest entrance are repeatedly interrupted by strikingly accurate back turns
      during which the ants stop and precisely gaze back to the nest entrance
      presumably to learn the landmark panorama of the nest surroundings. However, as
      at this point the complete navigational toolkit is not yet available, the ants
      are in need of a reference system for the compass component of the path
      integrator to align their nest entrance-directed gazes. In order to find this
      directional reference system, we systematically manipulated the skylight
      information received by ants during learning walks in their natural habitat, as
      it has been previously suggested that the celestial compass, as part of the path
      integrator, might provide such a reference system. High-speed video analyses of
      distinct learning walk elements revealed that even exclusion from the skylight
      polarization pattern, UV-light spectrum and the position of the sun did not alter
      the accuracy of the look back to the nest behavior. We therefore conclude that C.
      noda uses a different reference system to initially align their gaze directions.
      However, a comparison of neuroanatomical changes in the central complex and the
      mushroom bodies before and after learning walks revealed that exposure to UV
      light together with a naturally changing polarization pattern was essential to
      induce neuroplasticity in these high-order sensory integration centers of the ant
      brain. This suggests a crucial role of celestial information, in particular a
      changing polarization pattern, in initially calibrating the celestial compass
      system.

PMID- 29184488
TI  - Brain Maturation, Cognition and Voice Pattern in a Gender Dysphoria Case under
      Pubertal Suppression.
AB  - Introduction: Gender dysphoria (GD) (DMS-5) is a condition marked by increasing
      psychological suffering that accompanies the incongruence between one's
      experienced or expressed gender and one's assigned gender. Manifestation of GD
      can be seen early on during childhood and adolescence. During this period, the
      development of undesirable sexual characteristics marks an acute suffering of
      being opposite to the sex of birth. Pubertal suppression with gonadotropin
      releasing hormone analogs (GnRHa) has been proposed for these individuals as a
      reversible treatment for postponing the pubertal development and attenuating
      psychological suffering. Recently, increased interest has been observed on the
      impact of this treatment on brain maturation, cognition and psychological
      performance. Objectives: The aim of this clinical report is to review the effects
      of puberty suppression on the brain white matter (WM) during adolescence. WM
      Fractional anisotropy, voice and cognitive functions were assessed before and
      during the treatment. MRI scans were acquired before, and after 22 and 28 months
      of hormonal suppression. Methods: We performed a longitudinal evaluation of a
      pubertal transgender girl undergoing hormonal treatment with GnRH analog. Three
      longitudinal magnetic resonance imaging (MRI) scans were performed for diffusion
      tensor imaging (DTI), regarding Fractional Anisotropy (FA) for regions of
      interest analysis. In parallel, voice samples for acoustic analysis as well as
      executive functioning with the Wechsler Intelligence Scale (WISC-IV) were
      performed. Results: During the follow-up, white matter fractional anisotropy did
      not increase, compared to normal male puberty effects on the brain. After 22
      months of pubertal suppression, operational memory dropped 9 points and remained
      stable after 28 months of follow-up. The fundamental frequency of voice varied
      during the first year; however, it remained in the female range. Conclusion:
      Brain white matter fractional anisotropy remained unchanged in the GD girl during
      pubertal suppression with GnRHa for 28 months, which may be related to the
      reduced serum testosterone levels and/or to the patient's baseline low average
      cognitive performance.Global performance on the Weschler scale was slightly lower
      during pubertal suppression compared to baseline, predominantly due to a
      reduction in operational memory. Either a baseline of low average cognition or
      the hormonal status could play a role in cognitive performance during pubertal
      suppression. The voice pattern during the follow-up seemed to reflect
      testosterone levels under suppression by GnRHa treatment.

PMID- 29184489
TI  - Commentary: The Code for Facial Identity in the Primate Brain.

PMID- 29184490
TI  - Attractiveness Modulates Neural Processing of Infant Faces Differently in Males
      and Females.
AB  - Consistent attention and proper processing of infant faces by adults are
      essential for infant survival. Previous behavioral studies showed gender
      differences in processing infant cues (e.g., crying, laughing or facial
      attractiveness) and more importantly, the efforts invested in nurturing
      offspring. The underlying neural mechanisms of processing unknown infant faces
      provide hints for understanding behavioral differences. This functional magnetic
      resonance imaging (fMRI) study recruited 32 unmarried adult (16 females and 16
      males) participants to view unfamiliar infant faces and rate the attractiveness.
      Adult faces were also included. Behaviorally, despite that females and males
      showed no differences in attractiveness ratings of infant faces, a positive
      correlation was found between female's (but not male's) subjective liking for
      infants and attractiveness ratings of the infant faces. Functionally, brain
      activations to infant faces were modulated by attractiveness differently in males
      and females. Specifically, in female participants, activities in the ventromedial
      prefrontal cortex (vmPFC) and striatum/Nucleus Accumbens (NAcc) were positively
      modulated by infant facial attractiveness, and the modulation coefficients of
      these two regions were positively correlated. In male participants, infant facial
      attractiveness negatively modulated the activity in the dorsomedial prefrontal
      cortex (dmPFC). Our findings reveal that different neural mechanisms are involved
      in the processing of infant faces, which might lead to observed behavioral
      differences between males and females towards the baby.

PMID- 29184491
TI  - Computational and Experimental Approaches to Visual Aesthetics.
AB  - Aesthetics has been the subject of long-standing debates by philosophers and
      psychologists alike. In psychology, it is generally agreed that aesthetic
      experience results from an interaction between perception, cognition, and
      emotion. By experimental means, this triad has been studied in the field of
      experimental aesthetics, which aims to gain a better understanding of how
      aesthetic experience relates to fundamental principles of human visual perception
      and brain processes. Recently, researchers in computer vision have also gained
      interest in the topic, giving rise to the field of computational aesthetics. With
      computing hardware and methodology developing at a high pace, the modeling of
      perceptually relevant aspect of aesthetic stimuli has a huge potential. In this
      review, we present an overview of recent developments in computational aesthetics
      and how they relate to experimental studies. In the first part, we cover topics
      such as the prediction of ratings, style and artist identification as well as
      computational methods in art history, such as the detection of influences among
      artists or forgeries. We also describe currently used computational algorithms,
      such as classifiers and deep neural networks. In the second part, we summarize
      results from the field of experimental aesthetics and cover several isolated
      image properties that are believed to have a effect on the aesthetic appeal of
      visual stimuli. Their relation to each other and to findings from computational
      aesthetics are discussed. Moreover, we compare the strategies in the two fields
      of research and suggest that both fields would greatly profit from a joined
      research effort. We hope to encourage researchers from both disciplines to work
      more closely together in order to understand visual aesthetics from an integrated
      point of view.

PMID- 29184492
TI  - Functional Brain Imaging Synthesis Based on Image Decomposition and Kernel
      Modeling: Application to Neurodegenerative Diseases.
AB  - The rise of neuroimaging in research and clinical practice, together with the
      development of new machine learning techniques has strongly encouraged the
      Computer Aided Diagnosis (CAD) of different diseases and disorders. However,
      these algorithms are often tested in proprietary datasets to which the access is
      limited and, therefore, a direct comparison between CAD procedures is not
      possible. Furthermore, the sample size is often small for developing accurate
      machine learning methods. Multi-center initiatives are currently a very useful,
      although limited, tool in the recruitment of large populations and
      standardization of CAD evaluation. Conversely, we propose a brain image synthesis
      procedure intended to generate a new image set that share characteristics with an
      original one. Our system focuses on nuclear imaging modalities such as PET or
      SPECT brain images. We analyze the dataset by applying PCA to the original
      dataset, and then model the distribution of samples in the projected eigenbrain
      space using a Probability Density Function (PDF) estimator. Once the model has
      been built, we can generate new coordinates on the eigenbrain space belonging to
      the same class, which can be then projected back to the image space. The system
      has been evaluated on different functional neuroimaging datasets assessing the:
      resemblance of the synthetic images with the original ones, the differences
      between them, their generalization ability and the independence of the synthetic
      dataset with respect to the original. The synthetic images maintain the
      differences between groups found at the original dataset, with no significant
      differences when comparing them to real-world samples. Furthermore, they featured
      a similar performance and generalization capability to that of the original
      dataset. These results prove that these images are suitable for standardizing the
      evaluation of CAD pipelines, and providing data augmentation in machine learning
      systems -e.g. in deep learning-, or even to train future professionals at medical
      school.

PMID- 29184493
TI  - Step-to-Step Ankle Inversion/Eversion Torque Modulation Can Reduce Effort
      Associated with Balance.
AB  - Below-knee amputation is associated with higher energy expenditure during
      walking, partially due to difficulty maintaining balance. We previously found
      that once-per-step push-off work control can reduce balance-related effort, both
      in simulation and in experiments with human participants. Simulations also
      suggested that changing ankle inversion/eversion torque on each step, in response
      to changes in body state, could assist with balance. In this study, we
      investigated the effects of ankle inversion/eversion torque modulation on balance
      related effort among amputees (N = 5) using a multi-actuated ankle-foot
      prosthesis emulator. In stabilizing conditions, changes in ankle
      inversion/eversion torque were applied so as to counteract deviations in side-to
      side center-of-mass acceleration at the moment of intact-limb toe off; higher
      acceleration toward the prosthetic limb resulted in a corrective ankle inversion
      torque during the ensuing stance phase. Destabilizing controllers had the
      opposite effect, and a zero gain controller made no changes to the nominal
      inversion/eversion torque. To separate the balance-related effects of step-to
      step control from the potential effects of changes in average mechanics, average
      ankle inversion/eversion torque and prosthesis work were held constant across
      conditions. High-gain stabilizing control lowered metabolic cost by 13% compared
      to the zero gain controller (p = 0.05). We then investigated individual responses
      to subject-specific stabilizing controllers following an enforced exploration
      period. Four of five participants experienced reduced metabolic rate compared to
      the zero gain controller (-15, -14, -11, -6, and +4%) an average reduction of 9%
      (p = 0.05). Average prosthesis mechanics were unchanged across all conditions,
      suggesting that improvements in energy economy might have come from changes in
      step-to-step corrections related to balance. Step-to-step modulation of
      inversion/eversion torque could be used in new, active ankle-foot prostheses to
      reduce walking effort associated with maintaining balance.

PMID- 29184495
TI  - Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a
      Transgenic Mouse Model of Alzheimer's Disease.
AB  - Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and
      disrupted neural networks. Since only limited recovery is possible after the
      destruction of neural networks, preventing axonal degeneration during the early
      stages of disease progression is necessary to prevent AD. Polygalae Radix (roots
      of Polygala tenuifolia; PR) is a traditional herbal medicine used for sedation
      and amnesia. In this study, we aimed to clarify and analyze the preventive
      effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD.
      5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water
      extract of Polygalae Radix (PR extract) was orally administered to 4-month-old
      5XFAD mice that did not show signs of memory impairment. After consecutive
      administrations for 56 days, the PR extract prevented cognitive deficit and axon
      degeneration associated with the accumulation of amyloid beta (Abeta) plaques in
      the perirhinal cortex of the 5XFAD mice. PR extract did not influence the
      formation of Abeta plaques in the brain of the 5XFAD mice. In cultured neurons,
      the PR extract prevented axonal growth cone collapse and axonal atrophy induced
      by Abeta. Additionally, it prevented Abeta-induced endocytosis at the growth cone
      of cultured neurons. Our previous study reported that endocytosis inhibition was
      enough to prevent Abeta-induced growth cone collapse, axonal degeneration, and
      memory impairments. Therefore, the PR extract possibly prevented axonal
      degeneration and memory impairment by inhibiting endocytosis. PR is the first
      preventive drug candidate for AD that inhibits endocytosis in neurons.

PMID- 29184494
TI  - Aging Effect on Audiovisual Integrative Processing in Spatial Discrimination
      Task.
AB  - Multisensory integration is an essential process that people employ daily, from
      conversing in social gatherings to navigating the nearby environment. The aim of
      this study was to investigate the impact of aging on modulating multisensory
      integrative processes using event-related potential (ERP), and the validity of
      the study was improved by including "noise" in the contrast conditions. Older and
      younger participants were involved in perceiving visual and/or auditory stimuli
      that contained spatial information. The participants responded by indicating the
      spatial direction (far vs. near and left vs. right) conveyed in the stimuli using
      different wrist movements. electroencephalograms (EEGs) were captured in each
      task trial, along with the accuracy and reaction time of the participants' motor
      responses. Older participants showed a greater extent of behavioral improvements
      in the multisensory (as opposed to unisensory) condition compared to their
      younger counterparts. Older participants were found to have fronto-centrally
      distributed super-additive P2, which was not the case for the younger
      participants. The P2 amplitude difference between the multisensory condition and
      the sum of the unisensory conditions was found to correlate significantly with
      performance on spatial discrimination. The results indicated that the age-related
      effect modulated the integrative process in the perceptual and feedback stages,
      particularly the evaluation of auditory stimuli. Audiovisual (AV) integration may
      also serve a functional role during spatial-discrimination processes to
      compensate for the compromised attention function caused by aging.

PMID- 29184496
TI  - Andrographolide Protects against Aortic Banding-Induced Experimental Cardiac
      Hypertrophy by Inhibiting MAPKs Signaling.
AB  - Despite therapeutic advances, heart failure-related mortality rates remain high.
      Therefore, understanding the pathophysiological mechanisms involved in the
      remodeling process is crucial for the development of new therapeutic strategies.
      Andrographolide (Andr), a botanical compound, has potent cardio-protective
      effects due to its ability to inhibit mitogen-activated protein kinases (MAPKs).
      Andr has also been shown to inhibit inflammation and apoptosis, which are factors
      related to cardiac hypertrophy. Our aim was to evaluate the effects of Andr on
      cardiac hypertrophy and MAPKs activation. Thus, mice were subjected to aortic
      banding (AB) with/without Andr administration (25 mg/kg/day, orally). Cardiac
      function was accessed by echocardiography and hemodynamic parameters. Our results
      showed that Andr administration for 7 weeks decreased cardiac dysfunction and
      attenuated cardiac hypertrophy and fibrosis in AB mice. Andr treatment induced a
      strong reduction in the transcription of both hypertrophy (ANP, BNP, and beta
      MHC) and fibrosis related genes (collagen I, collagen III, CTGF, and TGFbeta). In
      addition, cardiomyocytes treated with Andr showed a reduced hypertrophic response
      to angiotensin II. Andr significantly inhibited MAPKs activation in both mouse
      hearts and cardiomyocytes. Treatment with a combination of MAPKs activators
      abolished the protective effects of Andr in cardiomyocytes. Furthermore, we found
      that Andr also inhibited the activation of cardiac fibroblasts via the MAPKs
      pathway, which was confirmed by the application of MAPKs inhibitors. In
      conclusion, Andr was found to confer a protective effect against experimental
      cardiac hypertrophy in mice, suggesting its potential as a novel therapeutic drug
      for pathological cardiac hypertrophy.

PMID- 29184497
TI  - Novel Two-Step Classifier for Torsades de Pointes Risk Stratification from Direct
      Features.
AB  - While pre-clinical Torsades de Pointes (TdP) risk classifiers had initially been
      based on drug-induced block of hERG potassium channels, it is now well
      established that improved risk prediction can be achieved by considering block of
      non-hERG ion channels. The current multi-channel TdP classifiers can be
      categorized into two classes. First, the classifiers that take as input the
      values of drug-induced block of ion channels (direct features). Second, the
      classifiers that are built on features extracted from output of the drug-induced
      multi-channel blockage simulations in the in-silico models (derived features).
      The classifiers built on derived features have thus far not consistently provided
      increased prediction accuracies, and hence casts doubt on the value of such
      approaches given the cost of including biophysical detail. Here, we propose a new
      two-step method for TdP risk classification, referred to as Multi-Channel
      Blockage at Early After Depolarization (MCB@EAD). In the first step, we
      classified the compound that produced insufficient hERG block as non
      torsadogenic. In the second step, the role of non-hERG channels to modulate TdP
      risk are considered by constructing classifiers based on direct or derived
      features at critical hERG block concentrations that generates EADs in the
      computational cardiac cell models. MCB@EAD provides comparable or superior TdP
      risk classification of the drugs from the direct features in tests against
      published methods. TdP risk for the drugs highly correlated to the propensity to
      generate EADs in the model. However, the derived features of the biophysical
      models did not improve the predictive capability for TdP risk assessment.

PMID- 29184498
TI  - Development of the Digital Arthritis Index, a Novel Metric to Measure Disease
      Parameters in a Rat Model of Rheumatoid Arthritis.
AB  - Despite a broad spectrum of anti-arthritic drugs currently on the market, there
      is a constant demand to develop improved therapeutic agents. Efficient compound
      screening and rapid evaluation of treatment efficacy in animal models of
      rheumatoid arthritis (RA) can accelerate the development of clinical candidates.
      Compound screening by evaluation of disease phenotypes in animal models
      facilitates preclinical research by enhancing understanding of human
      pathophysiology; however, there is still a continuous need to improve methods for
      evaluating disease. Current clinical assessment methods are challenged by the
      subjective nature of scoring-based methods, time-consuming longitudinal
      experiments, and the requirement for better functional readouts with relevance to
      human disease. To address these needs, we developed a low-touch, digital platform
      for phenotyping preclinical rodent models of disease. As a proof-of-concept, we
      utilized the rat collagen-induced arthritis (CIA) model of RA and developed the
      Digital Arthritis Index (DAI), an objective and automated behavioral metric that
      does not require human-animal interaction during the measurement and calculation
      of disease parameters. The DAI detected the development of arthritis similar to
      standard in vivo methods, including ankle joint measurements and arthritis
      scores, as well as demonstrated a positive correlation to ankle joint
      histopathology. The DAI also determined responses to multiple standard-of-care
      (SOC) treatments and nine repurposed compounds predicted by the SMarTRTM Engine
      to have varying degrees of impact on RA. The disease profiles generated by the
      DAI complemented those generated by standard methods. The DAI is a highly
      reproducible and automated approach that can be used in-conjunction with standard
      methods for detecting RA disease progression and conducting phenotypic drug
      screens.

PMID- 29184499
TI  - Aliskiren Improves Ischemia- and Oxygen Glucose Deprivation-Induced Cardiac
      Injury through Activation of Autophagy and AMP-Activated Protein Kinase.
AB  - Aliskiren is a direct renin inhibitor that has been effective in anti
      hypertension. We investigated whether aliskiren could improve the ischemia
      induced cardiac injury and whether the autophagy was involved in this effect. A
      myocardial infarction (MI) model was created by the ligation of the left anterior
      coronary artery in C57J/BL6 mice. They were treated for 1, 3, 7, and 14 days with
      vehicle or aliskiren (25 mg/kg/day via subcutaneous injection). In vivo, the MI
      mice exhibited worse cardiac function by echocardiographic assessment and showed
      larger myocardial scarring by light microscopy, whereas aliskiren treatment
      reversed these effects, which were also associated with the changes in caspase-3
      and Bcl-2 expression as well as in the number of apoptotic cells. Aliskiren
      increased autophagy, as demonstrated by LC3B-II expression and transmission
      electron microscopy. Furthermore, H9c2 cardiomyocytes were employed as an in
      vitro model to examine the effects of aliskiren on apoptosis and autophagy under
      oxygen glucose deprivation (OGD)-induced injury. Aliskiren significantly
      increased cell viability in a dose-dependent manner. The beneficial effects of
      aliskiren were associated with decreased apoptosis and mitochondrial membrane
      potential as well as increased autophagy via increased autophagosome formation.
      We also found that aliskiren-induced cardiomyocyte survival occurred via AMP
      activated protein kinase (AMPK)-dependent autophagy. Taken together, these
      results indicated that aliskiren increased cardiomyocyte survival through
      increased autophagosomal formation and decreased apoptosis and necrosis via
      modulating AMPK expression. AMPK-dependent autophagy may represent a novel
      mechanism for aliskiren in ischemic cardiac disease therapy.

PMID- 29184500
TI  - CaMKII Requirement for in Vivo Insular Cortex LTP Maintenance and CTA Memory
      Persistence.
AB  - Calcium-calmodulin/dependent protein kinase II (CaMKII) plays an essential role
      in LTP induction, but since it has the capacity to remain persistently activated
      even after the decay of external stimuli it has been proposed that it can also be
      necessary for LTP maintenance and therefore for memory persistence. It has been
      shown that basolateral amygdaloid nucleus (Bla) stimulation induces long-term
      potentiation (LTP) in the insular cortex (IC), a neocortical region implicated in
      the acquisition and retention of conditioned taste aversion (CTA). Our previous
      studies have demonstrated that induction of LTP in the Bla-IC pathway before CTA
      training increased the retention of this task. Although it is known that IC-LTP
      induction and CTA consolidation share similar molecular mechanisms, little is
      known about the molecular actors that underlie their maintenance. The purpose of
      the present study was to evaluate the role of CaMKII in the maintenance of in
      vivo Bla-IC LTP as well as in the persistence of CTA long-term memory (LTM). Our
      results show that acute microinfusion of myr-CaMKIINtide, a selective inhibitor
      of CaMKII, in the IC of adult rats during the late-phase of in vivo Bla-IC LTP
      blocked its maintenance. Moreover, the intracortical inhibition of CaMKII 24 h
      after CTA acquisition impairs CTA-LTM persistence. Together these results
      indicate that CaMKII is a central key component for the maintenance of
      neocortical synaptic plasticity as well as for persistence of CTA-LTM.

PMID- 29184501
TI  - Identification of a New Potent Inhibitor Targeting KRAS in Non-small Cell Lung
      Cancer Cells.
AB  - KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is an oncogenic
      driver with mutations in 30% of non-small cell lung cancer (NSCLC). However,
      there is no effective clinical drug even though it has been identified as an
      oncogene for 30 years. In this study, we identified a small molecule inhibitor
      compound 0375-0604 targeting KRAS by using molecular docking based virtual
      screening approach. Compound 0375-0604 had a good binding affinity to KRAS in
      vitro and exhibited cytotoxicity in oncogenic KRAS expressing NSCLC cell lines.
      Further mechanism study showed that compound 0375-0604 can block the formation of
      the complex of guanosine triphosphate (GTP) and KRAS in vitro. In addition,
      compound 0375-0604 inhibited KRAS downstream signaling pathway RAF/MEK/ERK and
      RAF/PI3K/AKT. Finally, we also found that this compound can inhibit the cell
      growth through G2/M cell cycle arrest and induce apoptosis on the NSCLC cell
      lines harboring KRAS mutation. Therefore, compound 0375-0604 may be considered as
      a potential KRAS inhibitor for treatment of NSCLC carrying KRAS oncogene.

PMID- 29184502
TI  - Editorial: Novel Therapeutic Targets and Emerging Treatments for Fibrosis.

PMID- 29184503
TI  - Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2
      yl)methyl]piperazines: Novel Antagonists for the Histamine H3 and H4 Receptors
      with Anti-inflammatory Potential.
AB  - The histamine receptors (HRs) are traditional G protein-coupled receptors of
      extensive therapeutic interest. Recently, H3R and H4R subtypes have been targeted
      in drug discovery projects for inflammation, asthma, pain, cancer, Parkinson's,
      and Alzheimer's diseases, which includes searches for dual acting H3R/H4R
      ligands. In the present work, nine 1-[(2,3-dihydro-1-benzofuran-2
      yl)methyl]piperazine (LINS01 series) molecules were synthesized and evaluated as
      H3R and H4R ligands. Our data show that the N-allyl-substituted compound
      LINS01004 bears the highest affinity for H3R (pKi 6.40), while the chlorinated
      compound LINS01007 has moderate affinity for H4R (pKi 6.06). In addition, BRET
      assays to assess the functional activity of Gi1 coupling indicate that all
      compounds have no intrinsic activity and act as antagonists of these receptors.
      Drug-likeness assessment indicated these molecules are promising leads for
      further improvements. In vivo evaluation of compounds LINS01005 and LINS01007 in
      a mouse model of asthma showed a better anti-inflammatory activity of LINS01007
      (3 g/kg) than the previously tested compound LINS01005. This is the first report
      with functional data of these compounds in HRs, and our results also show the
      potential of their applications as anti-inflammatory.

PMID- 29184505
TI  - Heart Rate Fragmentation: A Symbolic Dynamical Approach.
AB  - Background: We recently introduced the concept of heart rate fragmentation along
      with a set of metrics for its quantification. The term was coined to refer to an
      increase in the percentage of changes in heart rate acceleration sign, a
      dynamical marker of a type of anomalous variability. The effort was motivated by
      the observation that fragmentation, which is consistent with the breakdown of the
      neuroautonomic-electrophysiologic control system of the sino-atrial node, could
      confound traditional short-term analysis of heart rate variability. Objective:
      The objectives of this study were to: (1) introduce a symbolic dynamical approach
      to the problem of quantifying heart rate fragmentation; (2) evaluate how the
      distribution of the different dynamical patterns ("words") varied with the
      participants' age in a group of healthy subjects and patients with coronary
      artery disease (CAD); and (3) quantify the differences in the fragmentation
      patterns between the two sample populations. Methods: The symbolic dynamical
      method employed here was based on a ternary map of the increment NN interval time
      series and on the analysis of the relative frequency of symbolic sequences
      (words) with a pre-defined set of features. We analyzed annotated, open-access
      Holter databases of healthy subjects and patients with CAD, provided by the
      University of Rochester Telemetric and Holter ECG Warehouse (THEW). Results: The
      degree of fragmentation was significantly higher in older individuals than in
      their younger counterparts. However, the fragmentation patterns were different in
      the two sample populations. In healthy subjects, older age was significantly
      associated with a higher percentage of transitions from acceleration/deceleration
      to zero acceleration and vice versa (termed "soft" inflection points). In
      patients with CAD, older age was also significantly associated with higher
      percentages of frank reversals in heart rate acceleration (transitions from
      acceleration to deceleration and vice versa, termed "hard" inflection points).
      Compared to healthy subjects, patients with CAD had significantly higher
      percentages of soft and hard inflection points, an increased percentage of words
      with a high degree of fragmentation and a decreased percentage of words with a
      lower degree of fragmentation. Conclusion: The symbolic dynamical method employed
      here was useful to probe the newly recognized property of heart rate
      fragmentation. The findings from these cross-sectional studies confirm that CAD
      and older age are associated with higher levels of heart rate fragmentation.
      Furthermore, fragmentation with healthy aging appears to be phenotypically
      different from fragmentation in the context of CAD.

PMID- 29184504
TI  - The Anti-allergic Cromones: Past, Present, and Future.
AB  - The anti-allergic cromones were originally synthesized in the 1960s by Fisons
      Plc, and the first drug to emerge from this program, disodium cromoglycate was
      subsequently marketed for the treatment of asthma and other allergic conditions.
      Whilst early studies demonstrated that the ability of the cromones to prevent
      allergic reactions was due to their 'mast cell stabilizing' properties, the exact
      pharmacological mechanism by which this occurred, remained a mystery. Here, we
      briefly review the history of these drugs, recount some aspects of their
      pharmacology, and discuss two new explanations for their unique actions. We
      further suggest how these findings could be used to predict further uses for the
      cromones.

PMID- 29184506
TI  - Recent Advances in the Cellular and Molecular Mechanisms of Hypothalamic Neuronal
      Glucose Detection.
AB  - The hypothalamus have been recognized for decades as one of the major brain
      centers for the control of energy homeostasis. This area contains specialized
      neurons able to detect changes in nutrients level. Among them, glucose-sensing
      neurons use glucose as a signaling molecule in addition to its fueling role. In
      this review we will describe the different sub-populations of glucose-sensing
      neurons present in the hypothalamus and highlight their nature in terms of
      neurotransmitter/neuropeptide expression. This review will particularly discuss
      whether pro-opiomelanocortin (POMC) neurons from the arcuate nucleus are directly
      glucose-sensing. In addition, recent observations in glucose-sensing suggest a
      subtle system with different mechanisms involved in the detection of changes in
      glucose level and their involvement in specific physiological functions. Several
      data point out the critical role of reactive oxygen species (ROS) and
      mitochondria dynamics in the detection of increased glucose. This review will
      also highlight that ATP-dependent potassium (KATP) channels are not the only
      channels mediating glucose-sensing and discuss the new role of transient receptor
      potential canonical channels (TRPC). We will discuss the recent advances in the
      determination of glucose-sensing machinery and propose potential line of research
      needed to further understand the regulation of brain glucose detection.

PMID- 29184507
TI  - Kir2.1-Nav1.5 Channel Complexes Are Differently Regulated than Kir2.1 and Nav1.5
      Channels Alone.
AB  - Cardiac Kir2.1 and Nav1.5 channels generate the inward rectifier K+ (IK1) and the
      Na+ (INa) currents, respectively. There is a mutual interplay between the
      ventricular INa and IK1 densities, because Nav1.5 and Kir2.1 channels exhibit
      positive reciprocal modulation. Here we compared some of the biological
      properties of Nav1.5 and Kir2.1 channels when they are expressed together or
      separately to get further insights regarding their putative interaction. First we
      demonstrated by proximity ligation assays (PLAs) that in the membrane of
      ventricular myocytes Nav1.5 and Kir2.1 proteins are in close proximity to each
      other (<40 nm apart). Furthermore, intracellular dialysis with anti-Nav1.5 and
      anti-Kir2.1 antibodies suggested that these channels form complexes. Patch-clamp
      experiments in heterologous transfection systems demonstrated that the inhibition
      of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) decreased the INa and
      the IK1 generated by Nav1.5 and Kir2.1 channels when they were coexpressed, but
      not the IK1 generated by Kir2.1 channels alone, suggesting that complexes, but
      not Kir2.1 channels, are a substrate of CaMKII. Furthermore, inhibition of CaMKII
      precluded the interaction between Nav1.5 and Kir2.1 channels. Inhibition of 14-3
      3 proteins did not modify the INa and IK1 densities generated by each channel
      separately, whereas it decreased the INa and IK1 generated when they were
      coexpressed. However, inhibition of 14-3-3 proteins did not abolish the Nav1.5
      Kir2.1 interaction. Inhibition of dynamin-dependent endocytosis reduced the
      internalization of Kir2.1 but not of Nav1.5 or Kir2.1-Nav1.5 complexes.
      Inhibition of cytoskeleton-dependent vesicular trafficking via the
      dynein/dynactin motor increased the IK1, but reduced the INa, thus suggesting
      that the dynein/dynactin motor is preferentially involved in the backward and
      forward traffic of Kir2.1 and Nav1.5, respectively. Conversely, the
      dynein/dynactin motor participated in the forward movement of Kir2.1-Nav1.5
      complexes. Ubiquitination by Nedd4-2 ubiquitin-protein ligase promoted the Nav1.5
      degradation by the proteasome, but not that of Kir2.1 channels. Importantly, the
      Kir2.1-Nav1.5 complexes were degraded following this route as demonstrated by the
      overexpression of Nedd4-2 and the inhibition of the proteasome with MG132. These
      results suggested that Kir2.1 and Nav1.5 channels closely interact with each
      other leading to the formation of a pool of complexed channels whose biology is
      similar to that of the Nav1.5 channels.

PMID- 29184508
TI  - Non-motorized Treadmill Running Is Associated with Higher Cardiometabolic Demands
      Compared with Overground and Motorized Treadmill Running.
AB  - The aim of this study was to compare the cardiometabolic demands of running on a
      curved non-motorized treadmill (cNMT) with overground (OVR) and motorized
      treadmill (MOT) running. Fourteen trained male (n = 7) and female (n = 7) runners
      ([Formula: see text] 56.6 +/- 4.0 mL.kg-1.min-1) participated in the study. Each
      experimental session consisted of 5 * 6-min bouts of running at progressively
      higher speeds, separated by 6-min rest (females 9-15 km.h-1; males 10.5-16.5 km.h
      1). Oxygen consumption ([Formula: see text]) and heart rate (HR) during the last
      2 min of each bout were measured using a portable metabolic cart. Running at a
      set speed on the cNMT required a higher percentage of [Formula: see text] than
      OVR (mean +/- 90% CI, 22 +/- 6%; ES +/- 90% CI, 1.87 +/- 0.15) and MOT (16 +/-
      6%; ES 1.50 +/- 0.15) running. Similarly, HR during the cNMT was higher compared
      to OVR (25 +/- 9 beats.min-1, ES 1.23 +/- 0.14) and MOT (22 +/- 9 beats.min-1, ES
      1.35 +/- 0.13) trials. The decline in running economy observed during the cNMT
      trial was negatively related to body mass (R2 0.493, P = 0.01), indicating
      lighter runners were required to work at a higher relative intensity to overcome
      treadmill belt resistance. These data demonstrate the higher cardiometabolic
      demand associated with running at a given speed on the cNMT. It is critical these
      differences are taken into account when prescribing training intensities on the
      cNMT or translating data from the laboratory to an athletic setting.

PMID- 29184509
TI  - PARP-1 Variant Rs1136410 Confers Protection against Coronary Artery Disease in a
      Chinese Han Population: A Two-Stage Case-Control Study Involving 5643 Subjects.
AB  - Inhibition of poly(ADP-ribose) polymerase (PARP) may protect against coronary
      artery disease (CAD) in animal models, and rs1136410, a non-synonymous single
      nucleotide polymorphism (SNP) in PARP-1, has a potential impact on PARP
      activities in vitro. This two-stage case-control study, involving 2803 CAD
      patients and 2840 controls, aimed to investigate the associations of PARP-1
      rs1136410 with CAD development, lipid levels, PARP activities, 8-hydroxy-2'
      dexyguanosine (8-OHdG), and interleukin (IL)-6 levels in a Chinese Han
      population. Assuming a recessive model, the variant genotype GG of SNP rs1136410
      showed a significantly inverse association with CAD risk (adjusted odds ratio
      (OR) = 0.73, P < 0.001), left main coronary artery (LMCA) lesions (P = 0.003),
      vessel scores (P = 0.003), and modified Gensini scores (P < 0.001). There were
      significant correlations of SNP rs1136410 with higher levels of total cholesterol
      (TC) and lower levels of high-density lipoprotein cholesterol (HDL-c). In gene
      environment interaction analyses, participants with the variant genotype GG, but
      without smoking habit, type 2 diabetes mellitus, and hyperlipidemia, conferred an
      84% (P < 0.001) decreased risk of CAD. The genotype-phenotype correlation
      analyses further supported the functional roles of SNP rs1136410 in decreasing
      PARP activities and 8-OHdG levels. Taken together, our data suggest that SNP
      rs1136410 may confer protection against CAD through modulation of PARP activities
      and gene-environment interactions in a Chinese Han population.

PMID- 29184510
TI  - Neuronal and Glial Clocks Underlying Structural Remodeling of Pacemaker Neurons
      in Drosophila.
AB  - A number of years ago we reported that ventral Lateral Neurons (LNvs), which are
      essential in the control of rest-activity cycles in Drosophila, undergo circadian
      remodeling of their axonal projections. This structural plasticity gives rise to
      changes in the degree of connectivity, which could provide a means of
      transmitting time of day information. Thus far, work from different laboratories
      has shown that circadian remodeling of adult projections relies on activity
      dependent and -independent mechanisms. In terms of clock- dependent mechanisms,
      several neuronal types undergoing circadian remodeling hinted to a differential
      effect of clock genes; while per mutants exhibited poorly developed axonal
      terminals giving rise to low complexity arbors, tim mutants displayed a
      characteristic hyper branching phenotype, suggesting these genes could be playing
      additional roles to those ascribed to core clock function. To shed light onto
      this possibility we altered clock gene levels through RNAi- mediated
      downregulation and expression of a dominant negative form exclusively in the
      adult LNvs. These experiments confirmed that the LNv clock is necessary to drive
      the remodeling process. We next explored the contribution of glia to the
      structural plasticity of the small LNvs through acute disruption of their
      internal clock. Interestingly, impaired glial clocks also abolished circadian
      structural remodeling, without affecting other clock-controlled outputs. Taken
      together our data shows that both neuronal and glial clocks are recruited to
      define the architecture of the LNv projections along the day, thus enabling a
      precise reconfiguration of the circadian network.

PMID- 29184511
TI  - Dose-Response Relationship of Neuromuscular Training for Injury Prevention in
      Youth Athletes: A Meta-Analysis.
AB  - Background: Youth athletes with intensive sports participation are at an
      increased risk of sustaining injuries. Neuromuscular training programs reduce
      sports-related injury risk in this population, however, the dose-response
      relationship is largely unknown. Thus, the aim of this meta-analysis was to
      identify the optimal frequency, volume, duration, and period of neuromuscular
      training to prevent injuries in youth athletes. Methods: Computerized database
      searches (PubMed, Scopus, SPORTDiscus, The Cochrane Library, PEDro) were
      conducted in January 2017, with search terms related to youth sports,
      neuromuscular training, and injury prevention. Eligible trials (i) evaluated a
      neuromuscular training program; (ii) included youth athletes of 21 years or
      younger; (iii) had an analytical design (RCTs, quasi-experimental, cohort
      studies); (iv) contained original data; (v) and provided injury data. Two
      reviewers independently extracted data and assessed quality of eligible studies.
      Injury rate ratios (IRRs) for lower extremity injuries were pooled meta
      analytically, and moderator analyses examined the effect of training frequency,
      duration, volume, and period. Results: Data from 16 trials yielded an overall
      risk reduction of 42% with neuromuscular training (IRR = 0.58, 95%CI 0.47-0.72).
      Training frequencies of two (IRR = 0.50; 95%CI 0.29-0.86) or three times (IRR =
      0.40; 95%CI 0.31-0.53) per week revealed the largest risk reduction, and a weekly
      training volume of more than 30 min tended to be more effective compared to lower
      volumes. Programs with 10-15 min (IRR = 0.55; 95%CI 0.42-0.72) session duration
      produced effects comparable to those with longer session duration (IRR = 0.60;
      95%CI 0.46-0.76). Interventions lasting more than 6 months were not superior to
      shorter programs. Conclusion: This meta-analysis revealed that NMT performed in
      short bouts of 10-15 min, two to three times per week, with a weekly training
      volume of 30-60 min had the largest preventive effect for lower extremity
      injuries in youth athletes. These effects can be achieved within 20-60 sessions
      and training periods of <6 months. The present results are derived from a
      relatively small number of studies with heterogeneous methodological quality and
      should be treated with caution. The study was a priori registered at PROSPERO
      (CRD42016053473).

PMID- 29184513
TI  - Hoxa2 Inhibits Bone Morphogenetic Protein Signaling during Osteogenic
      Differentiation of the Palatal Mesenchyme.
AB  - Cleft palate is one of the most common congenital birth defects worldwide. The
      homeobox (Hox) family of genes are key regulators of embryogenesis, with Hoxa2
      having a direct role in secondary palate development. Hoxa2-/- mice exhibit cleft
      palate; however, the cellular and molecular mechanisms leading to cleft palate in
      Hoxa2-/- mice is largely unknown. Addressing this issue, we found that Hoxa2
      regulates spatial and temporal programs of osteogenic differentiation in the
      developing palate by inhibiting bone morphogenetic protein (BMP) signaling
      dependent osteoblast markers. Expression of osteoblast markers, including Runx2,
      Sp7, and AlpI were increased in Hoxa2-/- palatal shelves at embryonic day (E)
      13.5 and E15.5. Hoxa2-/- mouse embryonic palatal mesenchyme (MEPM) cells
      exhibited increased bone matrix deposition and mineralization in vitro. Moreover,
      loss of Hoxa2 resulted in increased osteoprogenitor cell proliferation and
      osteogenic commitment during early stages of palate development at E13.5.
      Consistent with upregulation of osteoblast markers, Hoxa2-/- palatal shelves
      displayed higher expression of canonical BMP signaling in vivo. Blocking BMP
      signaling in Hoxa2-/- primary MEPM cells using dorsomorphin restored cell
      proliferation and osteogenic differentiation to wild-type levels. Collectively,
      these data demonstrate for the first time that Hoxa2 may regulate palate
      development by inhibiting osteogenic differentiation of palatal mesenchyme via
      modulating BMP signaling.

PMID- 29184512
TI  - Strategies Developed to Induce, Direct, and Potentiate Bone Healing.
AB  - Bone exhibits a great ability for endogenous self-healing. Nevertheless, impaired
      bone regeneration and healing is on the rise due to population aging, increasing
      incidence of bone trauma and the clinical need for the development of alternative
      options to autologous bone grafts. Current strategies, including several
      biomolecules, cellular therapies, biomaterials, and different permutations of
      these, are now developed to facilitate the vascularization and the engraftment of
      the constructs, to recreate ultimately a bone tissue with the same properties and
      characteristics of the native bone. In this review, we browse the existing
      strategies that are currently developed, using biomolecules, cells and
      biomaterials, to induce, direct and potentiate bone healing after injury and
      further discuss the biological processes associated with this repair.

PMID- 29184514
TI  - Brain Tumor-Associated Psychosis and Spirituality-A Case Report.
AB  - This case report describes a patient with a dysembryogenic neuroepithelial tumor
      localized in the posterior thalamus and internal capsule, which presented with
      psychosis including religiously determined severe self-mutilation, auditory
      hallucinations, and rituals. The patient's history includes periodic
      religiousness over decades of her life suggesting that spirituality in this case
      might be a symptom of tumor progression. Our case reports on the topology-related
      effect of lesions on different brain networks involved in the phenomenology of
      the patient's psychotic symptoms.

PMID- 29184515
TI  - The Influence of Empathy and Morality of Violent Video Game Characters on Gamers'
      Aggression.
AB  - According to the General Aggression Model, situational factors (such as the game
      characters) and personal factors both affect a gamer's acquisition of aggressive
      behavior. Previous studies have found not only that the surface features of game
      characters, such as appearance and clothing, but also that their inherent
      characteristics, such as morality and identity, can influence a gamer's attitude
      and behavior. Research has also shown that empathy, as a personal factor, can
      protect gamers from the impact of media violence. However, past research has
      focused primarily on single factors affecting the player rather than more
      comprehensive investigations. This study investigates the influence of the game
      character's moral features and levels of empathy on the gamer's aggression. The
      participants were 120 Chinese university students (61 females and 59 males) with
      ages ranging from 17 to 27 years. Participants first completed a series of
      questionnaires: a user experience questionnaire, a video game questionnaire, the
      Buss-Perry Aggression Questionnaire, and a modified version of the Interpersonal
      Reactivity Index. All participants then had 5 min of practice playing a violent
      video game. They were then divided into three groups: a high empathy group, a low
      empathy group, and a no empathy group. After the practice, participants in the
      high and low empathy groups read empathy materials relating to the game
      characters; participants in the no empathy group began formal gameplay. All
      participants played the game for 20 min. Finally, participants were required to
      complete the Scale of Hostility Status questionnaire, the Implicit Aggression
      Test, and the Competitive Reaction Time Test. The results show that empathy and
      the morality of game characters both influence aggression, but empathy affected
      aggression differently in the participants playing justified roles (i.e., killing
      others for a moral reason in the game) compared to those playing unjustified
      roles (i.e., killing others for immoral reasons in the game). In the high empathy
      condition, the implicit aggression of justified players was significantly higher
      than those playing unjustified roles. However, high empathy does not always play
      a protective role, and its effect is restricted by the features of the game
      characters.

PMID- 29184516
TI  - Chasing the Rainbow: The Non-conscious Nature of Being.
AB  - Despite the compelling subjective experience of executive self-control, we argue
      that "consciousness" contains no top-down control processes and that
      "consciousness" involves no executive, causal, or controlling relationship with
      any of the familiar psychological processes conventionally attributed to it. In
      our view, psychological processing and psychological products are not under the
      control of consciousness. In particular, we argue that all "contents of
      consciousness" are generated by and within non-conscious brain systems in the
      form of a continuous self-referential personal narrative that is not directed or
      influenced in any way by the "experience of consciousness." This continuously
      updated personal narrative arises from selective "internal broadcasting" of
      outputs from non-conscious executive systems that have access to all forms of
      cognitive processing, sensory information, and motor control. The personal
      narrative provides information for storage in autobiographical memory and is
      underpinned by constructs of self and agency, also created in non-conscious
      systems. The experience of consciousness is a passive accompaniment to the non
      conscious processes of internal broadcasting and the creation of the personal
      narrative. In this sense, personal awareness is analogous to the rainbow which
      accompanies physical processes in the atmosphere but exerts no influence over
      them. Though it is an end-product created by non-conscious executive systems, the
      personal narrative serves the powerful evolutionary function of enabling
      individuals to communicate (externally broadcast) the contents of internal
      broadcasting. This in turn allows recipients to generate potentially adaptive
      strategies, such as predicting the behavior of others and underlies the
      development of social and cultural structures, that promote species survival.
      Consequently, it is the capacity to communicate to others the contents of the
      personal narrative that confers an evolutionary advantage-not the experience of
      consciousness (personal awareness) itself.

PMID- 29184517
TI  - Positive Healthy Organizations: Promoting Well-Being, Meaningfulness, and
      Sustainability in Organizations.
AB  - This contribution deals with the concept of healthy organizations and starts with
      a definition of healthy organizations and healthy business. In healthy
      organizations, culture, climate, and practices create an environment conducive to
      employee health and safety as well as organizational effectiveness (Lowe, 2010).
      A healthy organization thus leads to a healthy and successful business (De Smet
      et al., 2007; Grawitch and Ballard, 2016), underlining the strong link between
      organizational profitability and workers' well-being. Starting from a positive
      perspective focused on success and excellence, the contribution describes how
      positive organizational health psychology evolved from occupational health
      psychology to positive occupational health psychology stressing the importance of
      a primary preventive approach. The focus is not on deficiency and failure but on
      a positive organizational attitude that proposes interventions at different
      levels: individual, group, organization, and inter-organization. Healthy
      organizations need to find the right balance between their particular situation,
      sector, and culture, highlighting the importance of well-being and
      sustainability. This contribution discusses also the sustainability of work-life
      projects and the meaning of work in healthy organizations, stressing the
      importance of recognizing, respecting, and using the meaning of work as a key for
      growth and success. Finally, the contribution discusses new research and
      intervention opportunities for healthy organizations.

PMID- 29184519
TI  - Folk-Psychological Interpretation of Human vs. Humanoid Robot Behavior: Exploring
      the Intentional Stance toward Robots.
AB  - People rely on shared folk-psychological theories when judging behavior. These
      theories guide people's social interactions and therefore need to be taken into
      consideration in the design of robots and other autonomous systems expected to
      interact socially with people. It is, however, not yet clear to what degree the
      mechanisms that underlie people's judgments of robot behavior overlap or differ
      from the case of human or animal behavior. To explore this issue, participants (N
      = 90) were exposed to images and verbal descriptions of eight different behaviors
      exhibited either by a person or a humanoid robot. Participants were asked to rate
      the intentionality, controllability and desirability of the behaviors, and to
      judge the plausibility of seven different types of explanations derived from a
      recently proposed psychological model of lay causal explanation of human
      behavior. Results indicate: substantially similar judgments of human and robot
      behavior, both in terms of (1a) ascriptions of
      intentionality/controllability/desirability and in terms of (1b) plausibility
      judgments of behavior explanations; (2a) high level of agreement in judgments of
      robot behavior - (2b) slightly lower but still largely similar to agreement over
      human behaviors; (3) systematic differences in judgments concerning the
      plausibility of goals and dispositions as explanations of human vs. humanoid
      behavior. Taken together, these results suggest that people's intentional stance
      toward the robot was in this case very similar to their stance toward the human.

PMID- 29184518
TI  - Proposal Allocation Ratio as a Moderator of Interpersonal Responsibility Effects
      on Hostile Decision-Making in the Ultimatum Game.
AB  - Interpersonal responsibility is an indigenous Chinese personality construct,
      which is regarded to have positive social functions. Two studies were designed to
      explore the relationship among interpersonal responsibility, proposal allocation
      ratio, and responders' hostile decisions in an ultimatum game. Study 1 was a
      scenario study using a hypothetical ultimatum game with a valid sample of 551
      high school students. Study 2 was an experimental study which recruited 54
      undergraduate students to play the incentivized ultimatum game online. The
      results of the two studies showed a significantly negative correlation between
      interpersonal responsibility and responders' rejection responses only when the
      proposal allocation ratio was 3:7. In addition, in Study 2, interpersonal
      responsibility had negative effects on responders' rejection responses under the
      offer of 3:7, even after controlling for the Big Five personality traits. Taken
      together, proposal allocation ratio might moderate the effects of interpersonal
      responsibility on hostile decision-making in the ultimatum game. The social
      function of interpersonal responsibility might be beyond the Big Five.

PMID- 29184520
TI  - Proposed Diagnostic Criteria for Misophonia: A Multisensory Conditioned Aversive
      Reflex Disorder.

PMID- 29184521
TI  - Getting Better Acquainted with Auditory Voice Hallucinations (AVHs): A Need for
      Clinical and Social Change.

PMID- 29184523
TI  - Eysenck's Theory of Personality and the Role of Background Music in Cognitive
      Task Performance: A Mini-Review of Conflicting Findings and a New Perspective.
AB  - The question of whether background music is able to enhance cognitive task
      performance is of interest to scholars, educators, and stakeholders in business
      alike. Studies have shown that background music can have beneficial, detrimental
      or no effects on cognitive task performance. Extraversion-and its postulated
      underlying cause, cortical arousal-is regarded as an important factor influencing
      the outcome of such studies. According to Eysenck's theory of personality,
      extraverts' cortical arousal at rest is lower compared to that of introverts.
      Scholars have thus hypothesized that extraverts should benefit from background
      music in cognitive tasks, whereas introverts' performance should decline with
      music in the background. Reviewing studies that have considered extraversion as a
      mediator of the effect of background music on cognitive task performance, it is
      demonstrated that there is as much evidence in favor as there is against
      Eysenck's theory of personality. Further, revisiting Eysenck's concept of
      cortical arousal-which has traditionally been assessed by activity in the EEG
      alpha band-and reviewing literature on the link between extraversion and cortical
      arousal, it is revealed that there is conflicting evidence. Due to Eysenck's
      focus on alpha power, scholars have largely neglected higher frequency bands in
      the EEG signal as indicators of cortical arousal. Based on recent findings, it is
      suggested that beta power might not only be an indicator of alertness and
      attention but also a predictor of cognitive task performance. In conclusion, it
      is proposed that focused music listening prior to cognitive tasks might be a more
      efficient way to boost performance than listening to background music during
      cognitive tasks.

PMID- 29184522
TI  - Reconstructing Tone Sequences from Functional Magnetic Resonance Imaging Blood
      Oxygen Level Dependent Responses within Human Primary Auditory Cortex.
AB  - Here we show that, using functional magnetic resonance imaging (fMRI) blood
      oxygen level dependent (BOLD) responses in human primary auditory cortex, it is
      possible to reconstruct the sequence of tones that a person has been listening to
      over time. First, we characterized the tonotopic organization of each subject's
      auditory cortex by measuring auditory responses to randomized pure tone stimuli
      and modeling the frequency tuning of each fMRI voxel as a Gaussian in log
      frequency space. Then, we tested our model by examining its ability to work in
      reverse. Auditory responses were re-collected in the same subjects, except this
      time they listened to sequences of frequencies taken from simple songs (e.g.,
      "Somewhere Over the Rainbow"). By finding the frequency that minimized the
      difference between the model's prediction of BOLD responses and actual BOLD
      responses, we were able to reconstruct tone sequences, with mean frequency
      estimation errors of half an octave or less, and little evidence of systematic
      biases.

PMID- 29184524
TI  - A Qualitative Approach on Motives and Aspects of Risks in Freeriding.
AB  - Recent research has shown that there are multiple motives for participation in
      high-risk sport; however these results have come from studies that consider a
      number of different sports. Therefore, the aim of the present study was to better
      understand the motives and risk-related aspects of freeriding, using a
      qualitative approach. Semi-structured interviews were conducted with 40
      professional and semi-professional freeride skiers and snowboarders. All
      freeriders were highly experienced, of different age (19-44 years; 27.5 +/- 4.5
      years), gender (female = 13), and profession (professional athletes = 11).
      Analyses were done using MAXQDA software following a code theme approach. Mixed
      methods analyses using chi2-tests were computed for age (<25 years >=) and gender
      (female/male) on motives and risk factors. Five emerging themes were found,
      namely Challenge (n = 36), Friends (n = 31), Nature (n = 27), Balance (n = 26),
      and Freedom (n = 26). A sixth theme Habit (n = 13) was allocated as a subtheme
      due to minor responses. With regard to risk management, participants decided upon
      a risk calculation strategy which included multiple factors (e.g., planning,
      conditions, current situation, knowledge, and experience). Trusting in one's own
      abilities, avoiding negative fear and having trusted partners were among the risk
      factors. Deliberately seeking out dangerous situations was not a motive. chi2
      tests revealed no gender or age differences regarding aspects of risk (range of p
      scores: p = 0.17-1.00) or motives (p = 0.16-1.00). Freeriding was shown to
      provide positive effects through participation. Some important factors seem to be
      motivational drivers for freeriders: challenging oneself, experiencing nature,
      contributing to deep friendships, freeriding as a counterbalance to everyday life
      and escape from restrictions. Contrary to prior research reports on sensation
      seeking, experienced freeriders do not search the risk; they seem to minimize it
      based on knowledge and experience. Analyses of the present data did not show any
      gender or age differences, which may suggest that experience plays a more
      important role in high-risk sports than age or gender. Future research should
      qualitatively investigate further terrain based activities and implement motives
      and risk-related factors in quantitative research.

PMID- 29184525
TI  - Decomposing a Chunk into Its Elements and Reorganizing Them As a New Chunk: The
      Two Different Sub-processes Underlying Insightful Chunk Decomposition.
AB  - Familiar chunks can be processed highly efficiently, and this automatic process
      can prohibit the problem solver from developing novel and original ways to
      creatively solve difficult problems. For this reason, the role of the reverse
      process, chunk decomposition (CD), the process by which familiar patterns are
      broken down into their component elements in order to be regrouped in another
      meaningful manner, has been generally recognized as part of the creative process.
      However, previous studies on this issue have mainly focused on the decomposition
      process of CD (the D-process), while the reorganization process of CD has been
      greatly neglected or has not been distinctively identified in previous work. In
      this paper, we argue that the R-process could be equally as important as the D
      process for CD. Even if a problem solver manages to decompose a familiar chunk
      into its elements, he or she still may not solve the problem if these elements
      are not successfully organized in a new and meaningful manner. To investigate
      whether the cognitive mechanism of the R-process is different from that of the D
      process, we designed an experiment for detecting the effects of chunk tightness,
      which is regarded as the key factor in CD and which can be experimentally
      manipulated by the radical-level (loose) and stroke-level (tight) Chinese
      character CD tasks in the D-process, the R-process, and the more purified
      organization task (the O-process task) that does not involve the decomposition
      process. Our results showed that the stroke-level (tight) task was more difficult
      than the radical-level (loose) task for the D-process. However, for the R
      process, the stroke- and radical-level tasks showed no differences in
      performance. Moreover, for the more purified reorganization task, the O-process
      task, the radical-level organization and reorganization could be even more
      difficult than the stroke-level organization and reorganization. This result
      demonstrated that the cognitive processes underlying chunk decomposition and
      reorganization are fundamentally different. Therefore, more general concepts such
      as chunk restructuring that could include both D- and R-processes might be more
      suitable in accounting for this type of creative insight.

PMID- 29184527
TI  - Severity of Autism Symptoms and Degree of Attentional Difficulties Predicts
      Emotional and Behavioral Problems in Children with High-Functioning Autism; a Two
      Year Follow-up Study.
AB  - Children with autism often struggle with emotional and behavioral problems (EBP).
      This study investigated whether level of autism symptoms, attention problems or
      verbal IQ at baseline can predict EBP 2 years later in children with High
      Functioning Autism (HFA). Thirty-four participants with HFA and 45 typically
      developing children (TD) (ages 9-16) were assessed with parent ratings of EBP,
      autism symptoms, attention problems, and a test of verbal IQ. The amount of
      autism symptoms and degree of attention problems at baseline significantly
      predicted EBP at follow-up, whereas verbal IQ did not. The findings from this
      study emphasize the importance of assessing and understanding the consequences of
      autism symptoms and attention problems when treating EBP in children with HFA.
      Furthermore, interventions aimed at improving ASD symptoms may positively affect
      the prevalence of EBP in children with HFA.

PMID- 29184526
TI  - Loneliness, Resilience, Mental Health, and Quality of Life in Old Age: A
      Structural Equation Model.
AB  - Objectives: In the scientific literature on aging, a recent core issue has been
      the role of individuals' internal and external resources, which are considered
      intrinsically connected, in contributing synergistically to physical and
      psychological quality of life (QoL). The current study investigates the way in
      which psychological factors-such as, loneliness, resilience, and mental states,
      in terms of depression and anxiety symptoms-affect the perceived QoL among
      elderly individuals. Method: Data from 290 elderly Italian participants were used
      to study the mediation effects of both mental health and resilience to elucidate
      the relationship between loneliness and psychophysical QoL. Results: The best
      model we obtained supports the mediation effect of both resilience and mental
      health between loneliness and mental and physical QoL. These results highlight
      that loneliness influences mental and physical QoL via two pathways, with the
      impact of loneliness mediated by mental health and resilience dimensions.
      Conclusions: The findings suggest the importance of the support that elderly
      people receive from social relationships. In terms of clinical interventions, the
      reduction of loneliness could be an important factor in primary prevention or the
      recovery process. A way to reduce levels of mental distress could be represented
      by the increasing of resilience and self-efficacy and reduction of loneliness
      dissatisfaction. A high degree of resiliency contributes to increasing perceived
      life quality at the physical and psychological levels, and at the same time,
      reducing anxiety and depressive symptoms.

PMID- 29184528
TI  - Psychometric Properties of the German Version of the Health Regulatory Focus
      Scale.
AB  - The Health Regulatory Focus Scale (HRFS) is a short scale which measures an
      individual's prevention and promotion focus in a health-specific context. The
      main objective of this study was to examine the psychometric properties of the
      newly translated German version of the HRFS. Reliability and item characteristics
      were found to be satisfactory. Validity of both subscales toward other
      psychological constructs including behavioral approach and avoidance, core self
      evaluations, optimism, pessimism, neuroticism, as well as several measures of
      physical and mental health was shown. In addition, invariance of the measure
      across age and gender groups was shown. Exploratory as well as confirmatory
      factor analyses clearly indicated a two-factorial structure with a moderate
      correlation between the two latent constructs. Differences in health promotion
      and prevention focus between socio-demographic groups are discussed. The HRFS is
      found to be a valid and reliable instrument for the assessment of regulatory
      focus in health-related environments.

PMID- 29184529
TI  - The Changing Role of Health Care Professionals in Nursing Homes: A Systematic
      Literature Review of a Decade of Change.
AB  - Although the role of health care professionals is known to have changed over the
      last years, few formal efforts have been made to examine this change through
      means of a scientific review. Therefore, the goal of this paper was to
      investigate the changing role of health care professionals in nursing homes, as
      well as the conditions that make this change possible. A systematic review of
      health care literature published in the last decade (2007-2017) was utilized to
      address these goals. Our findings suggest that although health care in nursing
      homes is shifting from task-oriented care to relation-oriented care (e.g.,
      through an increased focus on patient dignity), various obstacles (e.g., negative
      self-image, work pressure, and a lack of developmental opportunities), needs
      (e.g., shared values, personal development, personal empowerment, team
      development, and demonstrating expertise), and competences (e.g., communication
      skills, attentiveness, negotiation skills, flexibility, teamwork, expertise, and
      coaching and leadership skills) still need to be addressed in order to
      successfully facilitate this change. As such, this paper provides various
      implications for health care research, health care institutions, practitioners,
      HR professionals and managers, and occupational health research.

PMID- 29184530
TI  - The Video Head Impulse Test to Assess the Efficacy of Vestibular Implants in
      Humans.
AB  - The purpose of this study was to evaluate whether it is possible to restore the
      high-frequency angular vestibulo-ocular reflex (aVOR) in patients suffering from
      a severe bilateral vestibulopathy (BV) and implanted with a vestibular implant
      prototype. Three patients (S1-3) participated in the study. They received a
      prototype vestibular implant with one to three electrode branches implanted in
      the proximity of the ampullary branches of the vestibular nerve. Five electrodes
      were available for electrical stimulation: one implanted in proximity of the left
      posterior ampullary nerve in S1, one in the left lateral and another one in the
      superior ampullary nerves in S2, and one in the right lateral and another one in
      the superior ampullary nerves in S3. The high-frequency aVOR was assessed using
      the video head impulse test (EyeSeeCam; EyeSeeTec, Munich, Germany), while motion
      modulated electrical stimulation was delivered via one of the implanted
      vestibular electrodes at a time. aVOR gains were compared to control measurements
      obtained in the same patients when the device was not activated. In three out of
      the five tested electrodes the aVOR gain increased monotonically with increased
      stimulation strength when head impulses were delivered in the plane of the
      implanted canal. In these cases, gains ranging from 0.4 to values above 1 were
      measured. A "reversed" aVOR could also be generated when inversed stimulation
      paradigms were used. In most cases, the gain for excitatory head impulses was
      superior to that recorded for inhibitory head impulses, consistent with
      unilateral vestibular stimulation. Improvements of aVOR gain were generally
      accompanied by a concomitant decrease of corrective saccades, providing
      additional evidence of an effective aVOR. High inter-electrode and inter-subject
      variability were observed. These results, together with previous research,
      demonstrate that it is possible to restore the aVOR in a broad frequency range
      using motion-modulated electrical stimulation of the vestibular afferents. This
      provides additional encouraging evidence of the possibility of achieving a useful
      rehabilitation alternative for patients with BV in the near future.

PMID- 29184531
TI  - Stent-Assisted Coiling of Ruptured and Incidental Aneurysms of the Intracranial
      Circulation Using Moderately Flow-Redirecting, Braided Leo Stents-Initial
      Experience in 39 Patients.
AB  - Background: Flow diversion (FD)-a young technique using stents with highly
      increased surface coverage-was introduced to treat complex aneurysms without
      intra-aneurysmal material placement and has amended the spectrum of endovascular
      techniques such as stent-assisted coil occlusion considerably. However, ischemic
      complications, a common side effect in FD, occur more frequently compared with
      the conventional endovascular approaches and certainly limit the indication of
      this technique. Our study aimed to investigate the feasibility and efficacy of
      stent-assisted coiling using low profile self-expandable stents, which exhibit
      only moderate flow-redirecting properties and therefore represent a combination
      of hemodynamic endovascular and occlusive endosaccular therapy. Materials and
      methods: 39 Patients were included in our retrospective study. Occlusion rates
      were assessed 6 months after the procedure in a total of 27 cases using the
      Raymond scale. Results: Complete occlusion (Raymond I) was achieved in 24/27
      aneurysms. Small neck remnants (Raymond II) were evident in 3/27 aneurysms. There
      were no cases with sac remnant or complete persistence of aneurysmal filling
      (Raymond III and IV). Conclusion: Our study demonstrates interventional treatment
      of intracranial aneurysms using flow-redirecting stent-assisted coiling to be
      technically feasible and highly effective in aneurysmal occlusion. We believe
      that this approach is outstanding in the prevention of long-term aneurysmal
      reperfusion and exhibits a more acceptable risk profile than highly efficient FD
      techniques.

PMID- 29184532
TI  - Early New Ischemic Lesions Located Outside the Initially Affected Vascular
      Territory Appear More Often in Stroke Patients with Elevated Glycated Hemoglobin
      (HbA1c).
AB  - Background: Early new ischemic lesions are common in patients with an acute
      ischemic stroke. These new ischemic lesions may represent the natural course of
      the initial stroke or de novo events. Objective: We hypothesized that early new
      ischemic lesions located outside the initially affected vascular territory would
      point at de novo events. Therefore, we differentiated new ischemic lesions
      located outside the initially affected vascular territory from those occurring
      only inside the initially affected vascular territory to identify risk factors
      that are associated with de novo events. Methods: Stroke patients underwent three
      magnetic resonance imaging examinations (at 3-T): on admission, on the next day
      and 4-7 days after symptom onset (clinicaltrials.gov: NCT00715533). Diffusion
      weighted imaging (DWI) lesions were delineated, coregistered, and then analyzed
      for new hyperintensities on follow-up examinations by raters blinded to clinical
      details. Patients were classified as having "new distant lesions" if new DWI
      lesions appeared outside or both outside and inside the initially affected
      vascular territory or "new local lesions" if they were only inside. Results: 115
      patients with early new DWI lesions constitute the study population. Sixteen
      patients (14%) had new distant lesions and 99 patients (86%) had new local
      lesions. In comparison between patients with new distant and new local lesions,
      patients with new distant lesions had significantly more often elevated glycated
      hemoglobin (HbA1c >= 6.5%; p = 0.022). Conclusion: Our data indicate that
      patients with elevated HbA1c have an increased risk for new, de novo ischemic
      lesions in the acute phase after an ischemic stroke.

PMID- 29184533
TI  - Correlations between Motor Symptoms across Different Motor Tasks, Quantified via
      Random Forest Feature Classification in Parkinson's Disease.
AB  - Background: Objective assessments of Parkinson's disease (PD) patients' motor
      state using motion capture techniques are still rarely used in clinical practice,
      even though they may improve clinical management. One major obstacle relates to
      the large dimensionality of motor abnormalities in PD. We aimed to extract global
      motor performance measures covering different everyday motor tasks, as a function
      of a clinical intervention, i.e., deep brain stimulation (DBS) of the subthalamic
      nucleus. Methods: We followed a data-driven, machine-learning approach and
      propose performance measures that employ Random Forests with probability
      distributions. We applied this method to 14 PD patients with DBS switched-off or 
      on, and 26 healthy control subjects performing the Timed Up and Go Test (TUG),
      the Functional Reach Test (FRT), a hand coordination task, walking 10-m straight,
      and a 90 degrees  curve. Results: For each motor task, a Random Forest identified
      a specific set of metrics that optimally separated PD off DBS from healthy
      subjects. We noted the highest accuracy (94.6%) for standing up. This
      corresponded to a sensitivity of 91.5% to detect a PD patient off DBS, and a
      specificity of 97.2% representing the rate of correctly identified healthy
      subjects. We then calculated performance measures based on these sets of metrics
      and applied those results to characterize symptom severity in different motor
      tasks. Task-specific symptom severity measures correlated significantly with each
      other and with the Unified Parkinson's Disease Rating Scale (UPDRS, part III,
      correlation of r2 = 0.79). Agreement rates between different measures ranged from
      79.8 to 89.3%. Conclusion: The close correlation of PD patients' various motor
      abnormalities quantified by different, task-specific severity measures suggests
      that these abnormalities are only facets of the underlying one-dimensional
      severity of motor deficits. The identification and characterization of this
      underlying motor deficit may help to optimize therapeutic interventions, e.g., to
      "automatically" adapt DBS settings in PD patients.

PMID- 29184534
TI  - Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset
      Multiple Sclerosis with No or Minimal Clinical Disability.
AB  - Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability
      to damage occurring during a period of active maturation of the human brain.
      Whereas adaptive mechanisms seem to take place in the POMS brain in the short
      medium term, natural history studies have shown that these patients reach
      irreversible disability, despite slower progression, at a significantly younger
      age than adult-onset MS (AOMS) patients. We tested for the first time whether
      significant brain alterations already occurred in POMS patients in their early
      adulthood and with no or minimal disability (n = 15) in comparison with age- and
      disability-matched AOMS patients (n = 14) and to normal controls (NC, n = 20). We
      used a multimodal MRI approach by modeling, using FSL, voxelwise measures of
      microstructural integrity of white matter tracts and gray matter volumes with
      those of intra- and internetwork functional connectivity (FC) (analysis of
      variance, p <= 0.01, corrected for multiple comparisons across space). POMS
      patients showed, when compared with both NC and AOMS patients, altered measures
      of diffusion tensor imaging (reduced fractional anisotropy and/or increased
      diffusivities) and higher probability of lesion occurrence in a clinically
      eloquent region for physical disability such as the posterior corona radiata. In
      addition, POMS patients showed, compared with the other two groups, reduced long
      range FC, assessed from resting functional MRI, between default mode network and
      secondary visual network, whose interaction subserves important cognitive
      functions such as spatial attention and visual learning. Overall, this pattern of
      structural damage and brain connectivity disruption in early adult POMS patients
      with no or minimal clinical disability might explain their unfavorable clinical
      outcome in the long term.

PMID- 29184535
TI  - Sex Differences in the Regulation of Offensive Aggression and Dominance by
      Arginine-Vasopressin.
AB  - Arginine-vasopressin (AVP) plays a critical role in the regulation of offensive
      aggression and social status in mammals. AVP is found in an extensive neural
      network in the brain. Here, we discuss the role of AVP in the regulation of
      aggression in the limbic system with an emphasis on the critical role of
      hypothalamic AVP in the control of aggression. In males, activation of AVP V1a
      receptors (V1aRs) in the hypothalamus stimulates offensive aggression, while in
      females activation of V1aRs inhibits aggression. Serotonin (5-HT) also acts
      within the hypothalamus to modulate the effects of AVP on aggression in a sex
      dependent manner. Activation of 5-HT1a receptors (5-HT1aRs) inhibits aggression
      in males and stimulates aggression in females. There are also striking sex
      differences in the mechanisms underlying the acquisition of dominance. In males,
      the acquisition of dominance is associated with the activation of AVP-containing
      neurons in the hypothalamus. By contrast, in females, the acquisition of
      dominance is associated with the activation of 5-HT-containing neurons in the
      dorsal raphe. AVP and 5-HT also play critical roles in the regulation of a form
      of social communication that is important for the maintenance of dominance
      relationships. In both male and female hamsters, AVP acts via V1aRs in the
      hypothalamus, as well as in other limbic structures, to communicate social status
      through the stimulation of a form of scent marking called flank marking. 5-HT
      acts on 5-HT1aRs as well as other 5-HT receptors within the hypothalamus to
      inhibit flank marking induced by AVP in both males and females. Interestingly,
      while AVP and 5-HT influence the expression of aggression in opposite ways in
      males and females, there are no sex differences in the effects of AVP and 5-HT on
      the expression of social communication. Given the profound sex differences in the
      incidence of many psychiatric disorders and the increasing evidence for a
      relationship between aggressiveness/dominance and the susceptibility to these
      disorders, understanding the neural regulation of aggression and social status
      will have significant import for translational studies.

PMID- 29184537
TI  - Probiotics Ingestion Does Not Directly Affect Thyroid Hormonal Parameters in
      Hypothyroid Patients on Levothyroxine Treatment.
AB  - Purpose: The relationship between probiotics and levothyroxine (LT4) requirement
      has not yet been investigated. The aim of this study was to assess whether a
      mixture of highly charged Lactobacilli and Bifidobacteria (VSL#3(r)) is able to
      influence LT4 metabolism acting on the gut microbiota. Methods: A prospective,
      randomized, single-blind, controlled, investigator-started clinical trial was
      carried out. Patients with primary hypothyroidism were randomly assigned to the
      study (VSL#3(r) + LT4) and the control group (LT4). A 2-month treatment phase was
      followed by 2 months of follow-up. Clinical examination, blood tests for thyroid
      function and for peripheral tissue markers of thyroid hormones (PTM) were
      performed monthly. LT4 dose adjustments were performed when necessary. Results:
      Thirty-nine patients were enrolled in the study group and 41 in the control
      group. No difference in thyroid function [thyroid-stimulating hormone (TSH), free
      triiodothyronine (fT3), and free thyroxine (fT4)] and PTM was found between
      groups and among visits. FT3/fT4 ratio was directly correlated to TSH at each
      visit in both groups, with the exception of the first evaluation of probiotics
      treated subjects (rho = 0.287, p = 0.076). LT4 daily dose adjustments occurred
      more frequently in the control than in the study group (p = 0.007), despite no
      differences in the mean LT4 daily dose. In particular, LT4 doses were increased
      six times in the control group and decreased four times in the study group.
      Conclusion: VSL#3(r) does not directly alter thyroid functional compensation. A
      probiotics-mediated influence on thyroid hormones homeostasis is suggested since
      probiotics supplementation could be able to prevent serum hormonal fluctuations.
      ClinicalTrialsgov ID: Registration number NCT03095963.

PMID- 29184538
TI  - Circulating Irisin Is Reduced in Male Patients with Type 1 and Type 2 Myotonic
      Dystrophies.
AB  - Context: Myotonic dystrophies (DM) are dominantly inherited muscle disorders
      characterized by myotonia, muscle weakness, and wasting. The reasons for
      sarcopenia in DMs are uncleared and multiple factors are involved. Irisin, a
      positive hormone regulator of muscle growth and bone, may play a role.
      Objectives: To investigate (1) circulating irisin in a series of DM1 and DM2 male
      patients compared with healthy controls and (2) the relationships between irisin
      and anthropometric, metabolic and hormonal parameters. Design and study
      participants: This is a cross-sectional study. Fasting blood samples for
      glucometabolic, gonadic, bone markers, and irisin were collected from 28
      ambulatory DM1, 10 DM2, and 23 age-matched healthy male subjects. Body
      composition and bone mineralization [bone mineral density (BMD)] were measured by
      DEXA. Echocardiographic assessment and visceral adiposity, namely, liver and
      epicardial fat, were investigated by ultrasound. Irisin released from cultured
      myotubes derived from 3 DM1, 3 DM2, and 3 healthy donors was assayed. Results:
      Plasma irisin levels were definitely lower in both DM1 and DM2 patients than in
      controls with no difference between DM1 and DM2. Irisin released from DM1 and DM2
      myotubes was similar to that released from myotubes of the non-DM donors, though
      diabetic DM2 myotubes released more irisin than DM1 myotubes. There was no
      correlation between irisin and muscle strength or lean mass in both DM1 and DM2
      patients. In DM1 patients, plasma irisin levels correlated negatively with oxygen
      consumption and positively with insulin resistance, while in DM2 patients plasma
      irisin levels positively correlated with fat mass at arms and legs levels. No
      correlation with visceral fat, left ventricular mass, and gonadal hormones could
      be detected. In both DM1 and DM2 patients, legs BMD parameters positively
      correlated with plasma irisin levels. Conclusion: Plasma irisin is reduced in
      both DM1 and DM2 male patients likely reflecting muscle mass reduction. Moreover,
      insulin resistance may contribute to modulation of plasma irisin in DM1 patients.
      The irisin-mediated cross talk muscle-adipose tissue-bone may be active also in
      the male myotonic dystrophies' model.

PMID- 29184539
TI  - Effects on Subclinical Heart Failure in Type 2 Diabetic Subjects on Liraglutide
      Treatment vs. Glimepiride Both in Combination with Metformin: A Randomized Open
      Parallel-Group Study.
AB  - Objective: We aimed to investigate the effect of liraglutide treatment on heart
      function in type 2 diabetes (T2D) patients with subclinical heart failure.
      Methods: Randomized open parallel-group trial. 62 T2D patients (45 male) with
      subclinical heart failure were randomized to either once daily liraglutide 1.8
      mg, or glimepiride 4 mg, both add on to metformin 1 g twice a day. Mitral annular
      systolic (s') and early diastolic (e') velocities were measured at rest and
      during bicycle ergometer exercise, using tissue Doppler echocardiography. The
      primary endpoint was 18-week treatment changes in longitudinal functional reserve
      index (LFRIdiastolic/systolic). Results: Clinical characteristics between groups
      (liraglutide = 33 vs. glimepiride = 29) were well matched. At baseline left
      ventricle ejection fraction (53.7 vs. 53.6%) and global longitudinal strain (
      15.3 vs. -16.5%) did not differ between groups. There were no significant
      differences in mitral flow velocities between groups. For the primary endpoint,
      there was no treatment change [95% confidence interval] for: LFRIdiastolic (-0.18
      vs. -0.53 [-0.28, 2.59; p = 0.19]), or LFRIsystolic (-0.10 vs. -0.18 [-1.0, 1.7;
      p = 0.54]); for the secondary endpoints, there was a significant treatment change
      in respect of body weight (-3.7 vs. -0.2 kg [-5.5, -1.4; p = 0.001]), waist
      circumference (-3.1 vs. -0.8 cm [-4.2, -0.4; p = 0.019]), and heart rate (HR)
      (6.3 vs. -2.3 bpm [-3.0, 14.2; p = 0.003]), with no such treatment change in
      hemoglobin A1c levels (-11.0 vs. -9.2 mmol/mol [-7.0, 2.6; p = 0.37]), between
      groups. Conclusion: 18-week treatment of liraglutide compared with glimepiride
      did not improve LFRIdiastolic/systolic, but however increased HR. There was a
      significant treatment change in body weight reduction in favor for liraglutide
      treatment.

PMID- 29184540
TI  - Ecogenomics and Taxonomy of Cyanobacteria Phylum.
AB  - Cyanobacteria are major contributors to global biogeochemical cycles. The genetic
      diversity among Cyanobacteria enables them to thrive across many habitats,
      although only a few studies have analyzed the association of phylogenomic clades
      to specific environmental niches. In this study, we adopted an ecogenomics
      strategy with the aim to delineate ecological niche preferences of Cyanobacteria
      and integrate them to the genomic taxonomy of these bacteria. First, an
      appropriate phylogenomic framework was established using a set of genomic
      taxonomy signatures (including a tree based on conserved gene sequences, genome
      to-genome distance, and average amino acid identity) to analyse ninety-nine
      publicly available cyanobacterial genomes. Next, the relative abundances of these
      genomes were determined throughout diverse global marine and freshwater
      ecosystems, using metagenomic data sets. The whole-genome-based taxonomy of the
      ninety-nine genomes allowed us to identify 57 (of which 28 are new genera) and 87
      (of which 32 are new species) different cyanobacterial genera and species,
      respectively. The ecogenomic analysis allowed the distinction of three major
      ecological groups of Cyanobacteria (named as i. Low Temperature; ii. Low
      Temperature Copiotroph; and iii. High Temperature Oligotroph) that were
      coherently linked to the genomic taxonomy. This work establishes a new taxonomic
      framework for Cyanobacteria in the light of genomic taxonomy and ecogenomic
      approaches.

PMID- 29184536
TI  - Insulin Resistance: Any Role in the Changing Epidemiology of Thyroid Cancer?
AB  - In the past few decades, the incidence of thyroid cancer (TC), namely of its
      papillary hystotype (PTC), has shown a steady increase worldwide, which has been
      attributed at least in part to the increasing diagnosis of early stage tumors.
      However, some evidence suggests that environmental and lifestyle factors can also
      play a role. Among the potential risk factors involved in the changing
      epidemiology of TC, particular attention has been drawn to insulin-resistance and
      related metabolic disorders, such as obesity, type 2 diabetes, and metabolic
      syndrome, which have been also rapidly increasing worldwide due to widespread
      dietary and lifestyle changes. In accordance with this possibility, various
      epidemiological studies have indeed gathered substantial evidence that insulin
      resistance-related metabolic disorders might be associated with an increased TC
      risk either through hyperinsulinemia or by affecting other TC risk factors
      including iodine deficiency, elevated thyroid stimulating hormone, estrogen
      dependent signaling, chronic autoimmune thyroiditis, and others. This review
      summarizes the current literature evaluating the relationship between metabolic
      disorders characterized by insulin resistance and the risk for TC as well as the
      possible underlying mechanisms. The potential implications of such association in
      TC prevention and therapy are discussed.

PMID- 29184542
TI  - Lysogenic Conversion of the Phytopathogen Ralstonia solanacearum by the P2virus
      phiRSY1.
AB  - A P2-like phage phiRSY1 infecting the phytopathogen Ralstonia solanacearum was
      isolated and characterized. The 40-kb genome of phiRSY1 showed high sequence
      similarity to the Ralstonia phage phiRSA1 and the GMI1000 prophage phiRSX. The
      major genomic differences between these phages were the different orientation of
      the int gene and the gene content close to the cosL. phiRSY1 and phiRSX use a 15
      base 3' portion of the serine tRNA(GGA) gene as attB, while phiRSA1 uses a 45
      base 3' portion of the arginine tRNA(CCG) gene. The different orientation of int
      in the genomes means that the gene arrangements in the prophage states are
      reversed in phiRSY1 and phiRSA1. Several putative gene products of phiRSY1 may
      affect the bacterium's fitness. phiRSY1 contains an open reading frame (ORF) that
      seems to encode a protein similar to Vgr in the type VI secretion system of
      various bacterial species. phiRSY1 lysogens showed phenotypic changes including
      enhanced twitching motility, large colony formation, and easy aggregation of
      cells, suggesting involvement of this ORF in the changes. In view of these phage
      gene arrangements, we surveyed prophages in the genomes of various R.
      solanacearum strains and found that the P2-like phages of R. solanacearum (14
      phages) consist of two major groups: the phiRSY1-type and the phiRSA1-type. The
      relationships and evolution of these P2-like phages inferred from our data are
      discussed in detail.

PMID- 29184543
TI  - Modulation of Microtubule Dynamics Affects Brucella abortus Intracellular
      Survival, Pathogen-Containing Vacuole Maturation, and Pro-inflammatory Cytokine
      Production in Infected Macrophages.
AB  - The microtubule (MT) cytoskeleton regulates several cellular processes related to
      the immune system. For instance, an intricate intracellular transport mediated by
      MTs is responsible for the proper localization of vesicular receptors of innate
      immunity and its adaptor proteins. In the present study, we used nocodazole to
      induce MTs depolymerization and paclitaxel or recombinant (r) TIR
      (Toll/interleukin-1 receptor) domain containing protein (TcpB) to induce MT
      stabilization in bone marrow-derived macrophages infected with Brucella abortus.
      Following treatment of the cells, we evaluated their effects on pathogen
      intracellular replication and survival, and in pro-inflammatory cytokine
      production. First, we observed that intracellular trafficking and maturation of
      Brucella-containing vesicles (BCVs) is affected by partial destabilization or
      stabilization of the MTs network. A typical marker of early BCVs, LAMP-1, is
      retained in late BCVs even 24 h after infection in the presence of low doses of
      nocodazole or paclitaxel and in the presence of different amounts of rTcpB.
      Second, microscopy and colony forming unit analysis revealed that bacterial load
      was increased in infected macrophages treated with lower doses of nocodazole or
      paclitaxel and with rTcpB compared to untreated cells. Third, innate immune
      responses were also affected by disturbing MT dynamics. MT depolymerization by
      nocodazole reduced IL-12 production in infected macrophages. Conversely, rTcpB
      treated cells augmented IL-12 and IL-1beta secretion in infected cells. In
      summary, these findings demonstrate that modulation of MTs affects several
      crucial steps of B. abortus pathogenesis, including BCV maturation, intracellular
      survival and IL-12 secretion in infected macrophages.

PMID- 29184544
TI  - Modeling Effects of Temperature, Soil, Moisture, Nutrition and Variety As
      Determinants of Severity of Pythium Damping-Off and Root Disease in Subterranean
      Clover.
AB  - Subterranean clover (Trifolium subterraneum) is a critical pasture legume in
      Mediterranean regions of southern Australia and elsewhere, including
      Mediterranean-type climatic regions in Africa, Asia, Australia, Europe, North
      America, and South America. Pythium damping-off and root disease caused by
      Pythium irregulare is a significant threat to subterranean clover in Australia
      and a study was conducted to define how environmental factors (viz. temperature,
      soil type, moisture and nutrition) as well as variety, influence the extent of
      damping-off and root disease as well as subterranean clover productivity under
      challenge by this pathogen. Relationships were statistically modeled using linear
      and generalized linear models and boosted regression trees. Modeling found
      complex relationships between explanatory variables and the extent of Pythium
      damping-off and root rot. Linear modeling identified high-level (4 or 5-way)
      significant interactions for each dependent variable (dry shoot and root weight,
      emergence, tap and lateral root disease index). Furthermore, all explanatory
      variables (temperature, soil, moisture, nutrition, variety) were found
      significant as part of some interaction within these models. A significant five
      way interaction between all explanatory variables was found for both dry shoot
      and root dry weights, and a four way interaction between temperature, soil,
      moisture, and nutrition was found for both tap and lateral root disease index. A
      second approach to modeling using boosted regression trees provided support for
      and helped clarify the complex nature of the relationships found in linear
      models. All explanatory variables showed at least 5% relative influence on each
      of the five dependent variables. All models indicated differences due to soil
      type, with the sand-based soil having either higher weights, greater emergence,
      or lower disease indices; while lowest weights and less emergence, as well as
      higher disease indices, were found for loam soil and low temperature. There was
      more severe tap and lateral root rot disease in higher moisture situations.

PMID- 29184541
TI  - Antagonistic Microbial Interactions: Contributions and Potential Applications for
      Controlling Pathogens in the Aquatic Systems.
AB  - Despite the active and intense treatment of wastewater, pathogenic microorganisms
      and viruses are frequently introduced into the aquatic environment. For most
      human pathogens, however, this is a rather hostile place, where starvation,
      continuous inactivation, and decay generally occur, rather than successful
      reproduction. Nevertheless, a great diversity of the pathogenic microorganisms
      can be detected, in particular, in the surface waters receiving wastewater.
      Pathogen survival depends majorly on abiotic factors such as irradiation, changes
      in water ionic strength, temperature, and redox state. In addition, inactivation
      is enhanced by the biotic interactions in the environment. Although knowledge of
      the antagonistic biotic interactions has been available since a long time,
      certain underlying processes and mechanisms still remain unclear. Others are well
      appreciated and increasingly are applied to the present research. Our review
      compiles and discusses the presently known biotic interactions between
      autochthonous microbes and pathogens introduced into the aquatic environment,
      including protozoan grazing, virus-induced bacterial cell lysis, antimicrobial
      substances, and predatory bacteria. An overview is provided on the present
      knowledge, as well as on the obvious research gaps. Individual processes that
      appear promising for future applications in the aquatic environment are presented
      and discussed.

PMID- 29184545
TI  - Comparison of the Effects of Phenylhydrazine Hydrochloride and Dicyandiamide on
      Ammonia-Oxidizing Bacteria and Archaea in Andosols.
AB  - Dicyandiamide, a routinely used commercial nitrification inhibitor (NI), inhibits
      ammonia oxidation catalyzed by ammonia monooxygenase (AMO). Phenylhydrazine
      hydrochloride has shown considerable potential for the development of next
      generation NIs targeting hydroxylamine dehydrogenase (HAO). The effects of the
      AMO inhibitor and the HAO inhibitor on ammonia-oxidizing bacteria (AOB) and
      ammonia-oxidizing archaea (AOA) present in agricultural soils have not been
      compared thus far. In the present study, the effects of the two inhibitors on
      soil nitrification and the abundance of AOA and AOB as well as their community
      structure were investigated in a soil microcosm using quantitative polymerase
      chain reaction and pyrosequencing. The net nitrification rates and the growth of
      AOA and AOB in this soil microcosm were inhibited by both NIs. Both NIs had
      limited effect on the community structure of AOB and no effect on that of AOA in
      this soil microcosm. The effects of phenylhydrazine hydrochloride were similar to
      those of dicyandiamide. These results indicated that organohydrazine-based NIs
      have potential for the development of next-generation NIs targeting HAO in the
      future.

PMID- 29184546
TI  - Amplicon-Metagenomic Analysis of Fungi from Antarctic Terrestrial Habitats.
AB  - In cold environments such as polar regions, microorganisms play important
      ecological roles, and most of our knowledge about them comes from studies of
      cultivable microorganisms. Metagenomic technologies are powerful tools that can
      give a more comprehensive assessment of microbial communities, and the
      amplification of rDNA followed by next-generation sequencing has given good
      results in studies aimed particularly at environmental microorganisms. Culture
      independent studies of microbiota in terrestrial habitats of Antarctica, which is
      considered the driest, coldest climate on Earth, are increasing and indicate that
      micro-diversity is much higher than previously thought. In this work, the
      microbial diversity of terrestrial habitats including eight islands of the South
      Shetland Archipelago, two islands on the Antarctic Peninsula and Union Glacier,
      was studied by amplicon-metagenome analysis. Molecular analysis of the studied
      localities clustered together the islands of the South Shetland Archipelago,
      except Greenwich Island, and separated them from the Litchfield and Lagotellerie
      islands and Union Glacier, which is in agreement with the latitudinal difference
      among them. Among fungi, 87 genera and 123 species were found, of which species
      belonging to 37 fungal genera not previously cultivated from Antarctica were
      detected. Phylogenetic analysis, including the closest BLAST-hit sequences,
      clustered fungi in 11 classes being the most represented Lecanoromycetes and
      Eurotiomycetes.

PMID- 29184547
TI  - Zinc Limitation Induces a Hyper-Adherent Goliath Phenotype in Candida albicans.
AB  - Pathogenic microorganisms often face acute micronutrient limitation during
      infection due to the action of host-mediated nutritional immunity. The human
      fungal pathogen Candida albicans is polymorphic and its morphological plasticity
      is one of its most widely recognized pathogenicity attributes. Here we
      investigated the effect of zinc, iron, manganese, and copper limitation on C.
      albicans morphology. Restriction of zinc specifically resulted in the formation
      of enlarged, spherical yeasts, a phenotype which we term Goliath cells. This
      cellular response to zinc restriction was conserved in C. albicans, C.
      dubliniensis and C. tropicalis, but not in C. parapsilosis, C. lusitaniae or
      Debaryomyces hansenii, suggesting that it may have emerged in the last common
      ancestor of these related pathogenic species. Cell wall analysis revealed
      proportionally more chitin exposure on the Goliath cell surface. Importantly,
      these cells were hyper-adherent, suggesting a possible role in pathogenicity.
      Interestingly, the zincophore-encoding gene PRA1 was expressed by Goliath cells
      in zinc limited media and lack of Pra1 inhibited both cellular enlargement and
      adhesion. Goliath cells represent a further layer of Candida phenotypic
      plasticity.

PMID- 29184548
TI  - Fused IgY Fc and Polysaccharide Adjuvant Enhanced the Immune Effect of the
      Recombinant VP2 and VP5 Subunits-A Prospect for Improvement of Infectious Bursal
      Disease Virus Subunit Vaccine.
AB  - Infectious bursal disease virus (IBDV) is a highly contagious pathogen that
      causes damage in lymphoid organs and remains a threat to the poultry industry
      worldwide. Currently, subunit vaccines based on VP2 antigen expressed in
      prokaryotic systems are widely used in clinical settings. However, the
      immunogenicity of VP2 vaccines is limited because of their inherent defect that
      the structure of the antigen expressed in Escherichia coli (E. coli) may be
      different from its natural conformation. In this study, we fused VP2 and VP5
      protective antigen genes and linked the chicken IgY Fc gene onto it. The
      eukaryotic expression plasmid carrying the fusion gene was transformed into
      Pichia pastoris (P. pastoris) to express the recombinant VP2-VP5-Fc protein. The
      recombinant protein was used as immunogen for evaluating immune response, and the
      recombinant VP2-Fc and VP2 proteins expressed in P. pastoris and the commercial
      VP2 subunit vaccines were used as controls. Moreover, Taishan Pinus massoniana
      pollen polysaccharide (TPPPS), an immunomodulator found by our laboratory, was
      used as adjuvant to investigate its immune modulatory effects on immunogens.
      Chickens were divided into six groups and inoculated with VP2-VP5-Fc+TPPPS, VP2
      VP5-Fc, VP2-Fc, VP2 vaccine, commercial VP2 subunit vaccine, and phosphate
      buffered saline (PBS). The recombinant VP2 subunit vaccine expressed in P.
      pastoris exhibited higher immunogenicity than the commercial VP2 subunit vaccine.
      The VP2-Fc protein showed a better effect than the VP2 protein, and the VP2-VP5
      Fc subunit further improved the immune effects. In addition, TPPPS was proved to
      be a good immunopotentiator for the VP2-VP5-Fc subunit vaccine. Hence, the
      recombinant VP2-VP5-Fc subunit combined with TPPPS adjuvant exhibits potential as
      efficient IBDV vaccine to prevent infectious bursal disease.

PMID- 29184549
TI  - The Immunology of Wild Rodents: Current Status and Future Prospects.
AB  - Wild animals' immune responses contribute to their evolutionary fitness. These
      responses are moulded by selection to be appropriate to the actual antigenic
      environment in which the animals live, but without imposing an excessive
      energetic demand which compromises other component of fitness. But, exactly what
      these responses are, and how they compare with those of laboratory animals, has
      been little studied. Here, we review the very small number of published studies
      of immune responses of wild rodents, finding general agreement that their humoral
      (antibody) responses are highly elevated when compared with those of laboratory
      animals, and that wild rodents' cellular immune system reveals extensive
      antigenic exposure. In contrast, proliferative and cytokine responses of ex vivo
      stimulated immune cells of wild rodents are typically depressed compared with
      those of laboratory animals. Collectively, these responses are appropriate to
      wild animals' lives, because the elevated responses reflect the cumulative
      exposure to infection, while the depressed proliferative and cytokine responses
      are indicative of effective immune homeostasis that minimizes immunopathology. A
      more comprehensive understanding of the immune ecology of wild animals requires
      (i) understanding the antigenic load to which wild animals are exposed, and
      identification of any key antigens that mould the immune repertoire, (ii)
      identifying immunoregulatory processes of wild animals and the events that induce
      them, and (iii) understanding the actual resource state of wild animals, and the
      immunological consequences that flow from this. Together, by extending studies of
      wild rodents, particularly addressing these questions (while drawing on our
      immunological understanding of laboratory animals), we will be better able to
      understand how rodents' immune responses contribute to their fitness in the wild.

PMID- 29184551
TI  - Interleukin-4 Supports the Suppressive Immune Responses Elicited by Regulatory T
      Cells.
AB  - Interleukin-4 (IL-4) has been considered as one of the tolerogenic cytokines in
      many autoimmune animal models and clinical settings. Despite its role in
      antagonizing pathogenic Th1 responses, little is known about whether IL-4
      possesses functions that affect regulatory T cells (Tregs). Tregs are specialized
      cells responsible for the maintenance of peripheral tolerance through their
      immune modulatory capabilities. Interestingly, it has been suggested that IL-4
      supplement at a high concentration protects responder T cells (Tresps) from Treg
      mediated immune suppression. In addition, such supplement also impedes TGF-beta
      induced Treg differentiation in vitro. However, these phenomena may contradict
      the tolerogenic role of IL-4, and the effects of IL-4 on Tregs are therefore
      needed to be further elucidated. In this study, we utilized IL-4 knockout (KO)
      mice to validate the role of IL-4 on Treg-mediated immune suppression. Although
      IL-4 KO and control animals harbor similar frequencies of Tregs, Tregs from IL-4
      KO mice weakly suppressed autologous Tresp activation. In addition, IL-4
      deprivation impaired the ability of Tregs to modulate immune response, whereas IL
      4 supplementation reinforced IL-4 KO Tregs in their function in suppressing
      Tresps. Finally, the presence of IL-4 was associated with increased cell survival
      and granzyme expression of Tregs. These results suggest the essential role of IL
      4 in supporting Treg-mediated immune suppression, which may benefit the
      development of therapeutic strategies for autoimmune diseases.

PMID- 29184553
TI  - Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low
      Sensitization to Infection.
AB  - Tumor necrosis factor-alpha (TNF-alpha) blockade is an effective treatment for
      rheumatoid arthritis (RA) and other inflammatory diseases, but in patients, it is
      associated with reduced resistance to the infectious agents Mycobacterium
      tuberculosis and Listeria monocytogenes, among others. Our goal was to model
      infection and arthritis in mice and to compare etanercept, a currently used anti
      TNF-alpha inhibitor, to an anti-TNF-alpha vaccine. We developed a murine
      surrogate of the TNF-alpha kinoid and produced an anti-murine TNF-alpha vaccine
      (TNFKi) composed of keyhole limpet hemocyanin conjugated to TNF-alpha, which
      resulted in anti-TNF-alpha antibody production in mice. We also used etanercept
      (a soluble receptor of TNF commonly used to treat RA) as a control of TNF
      neutralization. In a mouse model of collagen-induced arthritis, TNFKi protected
      against inflammation similar to etanercept. In a mouse model of acute L.
      monocytogenes infection, all TNFKi-treated mice showed cleared bacterial
      infection and survived, whereas etanercept-treated mice showed large liver
      granulomas and quickly died. Moreover, TNFKi mice infected with the virulent
      H37Rv M. tuberculosis showed resistance to infection, in contrast with etanercept
      treated mice or controls. Depending on the TNF-alpha blockade strategy, treating
      arthritis with a TNF-alpha inhibitor could result in a different profile of
      infection suceptibility. Our TNFKi vaccine allowed for a better remaining host
      defense than did etanercept.

PMID- 29184550
TI  - Natural Killer Cell Interactions with Classical and Non-Classical Human Leukocyte
      Antigen Class I in HIV-1 Infection.
AB  - Natural killer (NK) cells are effector lymphocytes of the innate immune system
      that are able to mount a multifaceted antiviral response within hours following
      infection. This is achieved through an array of cell surface receptors
      surveilling host cells for alterations in human leukocyte antigen class I (HLA-I)
      expression and other ligands as signs of viral infection, malignant
      transformation, and cellular stress. This interaction between HLA-I ligands and
      NK-cell receptor is not only important for recognition of diseased cells but also
      mediates tuning of NK-cell-effector functions. HIV-1 alters the expression of HLA
      I ligands on infected cells, rendering them susceptible to NK cell-mediated
      killing. However, over the past years, various HIV-1 evasion strategies have been
      discovered to target NK-cell-receptor ligands and allow the virus to escape from
      NK cell-mediated immunity. While studies have been mainly focusing on the role of
      polymorphic HLA-A, -B, and -C molecules, less is known about how HIV-1 affects
      the more conserved, non-classical HLA-I molecules HLA-E, -G, and -F. In this
      review, we will focus on the recent progress in understanding the role of non
      classical HLA-I ligands in NK cell-mediated recognition of HIV-1-infected cells.

PMID- 29184554
TI  - IL-17 and TNF-alpha Are Key Mediators of Moraxella catarrhalis Triggered
      Exacerbation of Allergic Airway Inflammation.
AB  - Alterations of the airway microbiome are often associated with pulmonary
      diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis
      in the upper airways is linked with an increased risk to develop or exacerbate
      asthma. However, the mechanisms by which M. catarrhalis augments allergic airway
      inflammation (AAI) remain unclear. We here characterized the cellular and soluble
      mediators of M. catarrhalis triggered excacerbation of AAI in wt and IL-17
      deficient as well as in animals treated with TNF-alpha and IL-6 neutralizing
      antibodies. We compared the type of inflammatory response in M. catarrhalis
      infected, house dust mite (HDM)-allergic and animals infected with M. catarrhalis
      at different time points of HDM sensitization. We found that airway infection of
      mice with M. catarrhalis triggers a strong inflammatory response with massive
      neutrophilic infiltrates, high amounts of IL-6 and TNF-alpha and moderate levels
      of CD4+ T-cell-derived IFN-gamma and IL-17. If bacterial infection occurred
      during HDM allergen sensitization, the allergic airway response was exacerbated,
      particularly by the expansion of Th17 cells and increased TNF-alpha levels.
      Neutralization of IL-17 or TNF-alpha but not IL-6 resulted in accelerated
      clearance of M. catarrhalis and effectively prevented infection-induced
      exacerbation of AAI. Taken together, our data demonstrate an essential role for
      TNF-alpha and IL-17 in infection-triggered exacerbation of AAI.

PMID- 29184552
TI  - Multifaceted Effects of Extracellular Adenosine Triphosphate and Adenosine in the
      Tumor-Host Interaction and Therapeutic Perspectives.
AB  - Cancer is still one of the world's most pressing health-care challenges, leading
      to a high number of deaths worldwide. Immunotherapy is a new developing therapy
      that boosts patient's immune system to fight cancer by modifying tumor-immune
      cells interaction in the tumor microenvironment (TME). Extracellular adenosine
      triphosphate (eATP) and adenosine (Ado) are signaling molecules released in the
      TME that act as modulators of both immune and tumor cell responses. Extracellular
      adenosine triphosphate and Ado activate purinergic type 2 (P2) and type 1 (P1)
      receptors, respectively, triggering the so-called purinergic signaling. The
      concentration of eATP and Ado within the TME is tightly controlled by several
      cell-surface ectonucleotidases, such as CD39 and CD73, the major ecto-enzymes
      expressed in cancer cells, immune cells, stromal cells, and vasculature, being
      CD73 also expressed on tumor-associated fibroblasts. Once accumulated in the TME,
      eATP boosts antitumor immune response, while Ado attenuates or suppresses
      immunity against the tumor. In addition, both molecules can mediate growth
      stimulation or inhibition of the tumor, depending on the specific receptor
      activated. Therefore, purinergic signaling is able to modulate both tumor and
      immune cells behavior and, consequently, the tumor-host interaction and disease
      progression. In this review, we discuss the role of purinergic signaling in the
      host-tumor interaction detailing the multifaceted effects of eATP and Ado in the
      inflammatory TME. Moreover, we present recent findings into the application of
      purinergic-targeting therapy as a potential novel option to boost antitumor
      immune responses in cancer.

PMID- 29184555
TI  - Innate Immunity to Respiratory Infection in Early Life.
AB  - Early life is a period of particular susceptibility to respiratory infections and
      symptoms are frequently more severe in infants than in adults. The neonatal
      immune system is generally held to be deficient in most compartments; responses
      to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory
      activity and adaptive lymphocyte responses are limited, leading to poor immune
      memory and ineffective vaccine responses. For mucosal surfaces such as the lung,
      which is continuously exposed to airborne antigen and to potential pathogenic
      invasion, the ability to discriminate between harmless and potentially dangerous
      antigens is essential, to prevent inflammation that could lead to loss of gaseous
      exchange and damage to the developing lung tissue. We have only recently begun to
      define the differences in respiratory immunity in early life and its
      environmental and developmental influences. The innate immune system may be of
      relatively greater importance than the adaptive immune system in the neonatal and
      infant period than later in life, as it does not require specific antigenic
      experience. A better understanding of what constitutes protective innate immunity
      in the respiratory tract in this age group and the factors that influence its
      development should allow us to predict why certain infants are vulnerable to
      severe respiratory infections, design treatments to accelerate the development of
      protective immunity, and design age specific adjuvants to better boost immunity
      to infection in the lung.

PMID- 29184556
TI  - GATA3 Regulates the Development and Functions of Innate Lymphoid Cell Subsets at
      Multiple Stages.
AB  - Innate lymphoid cells (ILCs) are regarded as the innate counterpart of effector
      CD4 T helper (Th) cells. Just as Th cells, ILCs are classified into distinct
      subsets based on their functions that are delivered mainly through effector
      cytokine production. Both ILCs and Th cells play critical roles in various
      protective immune responses and inflammatory diseases. Similar to Th cell
      differentiation, the development of ILC subsets depends on several master
      transcription factors, among which GATA3 is critical for the development and
      maintenance of type 2 ILCs (ILC2s). However, GATA3 is expressed by all ILC
      subsets and ILC progenitors, albeit at different levels. In a striking parallel
      with GATA3 function in T cell development and differentiation, GATA3 also has
      multiple functions in different ILCs at various stages. In this review, I will
      discuss how quantitative and dynamic expression of GATA3 regulates the
      development and functions of ILC subsets.

PMID- 29184557
TI  - Combined Genomic and Genetic Data Integration of Major Agronomical Traits in
      Bread Wheat (Triticum aestivum L.).
AB  - The high resolution integration of bread wheat genetic and genomic resources
      accumulated during the last decades offers the opportunity to unveil candidate
      genes driving major agronomical traits to an unprecedented scale. We combined 27
      public quantitative genetic studies and four genetic maps to deliver an
      exhaustive consensus map consisting of 140,315 molecular markers hosting 221, 73,
      and 82 Quantitative Trait Loci (QTL) for respectively yield, baking quality, and
      grain protein content (GPC) related traits. Projection of the consensus genetic
      map and associated QTLs onto the wheat syntenome made of 99,386 genes ordered on
      the 21 chromosomes delivered a complete and non-redundant repertoire of 18, 8, 6
      metaQTLs for respectively yield, baking quality and GPC, altogether associated to
      15,772 genes (delivering 28,630 SNP-based makers) including 37 major candidates.
      Overall, this study illustrates a translational research approach in transferring
      information gained from grass relatives to dissect the genomic regions hosting
      major loci governing key agronomical traits in bread wheat, their flanking
      markers and associated candidate genes to be now considered as a key resource for
      breeding programs.

PMID- 29184558
TI  - Application of Genome Wide Association and Genomic Prediction for Improvement of
      Cacao Productivity and Resistance to Black and Frosty Pod Diseases.
AB  - Chocolate is a highly valued and palatable confectionery product. Chocolate is
      primarily made from the processed seeds of the tree species Theobroma cacao.
      Cacao cultivation is highly relevant for small-holder farmers throughout the
      tropics, yet its productivity remains limited by low yields and widespread
      pathogens. A panel of 148 improved cacao clones was assembled based on
      productivity and disease resistance, and phenotypic single-tree replicated clonal
      evaluation was performed for 8 years. Using high-density markers, the diversity
      of clones was expressed relative to 10 known ancestral cacao populations, and
      significant effects of ancestry were observed in productivity and disease
      resistance. Genome-wide association (GWA) was performed, and six markers were
      significantly associated with frosty pod disease resistance. In addition, genomic
      selection was performed, and consistent with the observed extensive linkage
      disequilibrium, high predictive ability was observed at low marker densities for
      all traits. Finally, quantitative trait locus mapping and differential expression
      analysis of two cultivars with contrasting disease phenotypes were performed to
      identify genes underlying frosty pod disease resistance, identifying a
      significant quantitative trait locus and 35 differentially expressed genes using
      two independent differential expression analyses. These results indicate that in
      breeding populations of heterozygous and recently admixed individuals, mapping
      approaches can be used for low complexity traits like pod color cacao, or in
      other species single gene disease resistance, however genomic selection for
      quantitative traits remains highly effective relative to mapping. Our results can
      help guide the breeding process for sustainable improved cacao productivity.

PMID- 29184559
TI  - State of the Art: trxG Factor Regulation of Post-embryonic Plant Development.
AB  - Multicellular organisms rely on the precise and consistent regulation of gene
      expression to direct their development in tissue- and cell-type specific
      patterns. This regulatory activity involves arrays of DNA-binding transcription
      factors and epigenetic factors that modify chromatin structure. Among the
      chromatin modifiers, trithorax (trxG) and Polycomb (PcG) group proteins play
      important roles in orchestrating the stable activation and repression of gene
      expression, respectively. These proteins have generally antagonistic functions in
      maintaining cell and tissue homeostasis as well as in mediating widespread
      transcriptional reprogramming during developmental transitions. Plants utilize
      multiple trxG factors to regulate gene transcription as they modulate their
      development in response to both endogenous and environmental cues. Here, I will
      discuss the roles of trxG factors and their associated proteins in post-embryonic
      plant development.

PMID- 29184560
TI  - Volatile Metabolomic Composition of Vitex Species: Chemodiversity Insights and
      Acaricidal Activity.
AB  - The Vitex genus (Lamiaceae) produces a plethora of metabolites that include
      ecdysteroids and terpenoids, some of which have demonstrated insect repellent
      properties. The volatile composition of several members of this genus has not
      been chemically defined, as many taxa are endemic to remote ecosystems. In this
      study, leaves were collected from the northeast of Brazil from Vitex capitata, V.
      megapotamica, V. gardneriana, and V. rufescens plants and examined for their
      chemical profile via GC-MS/FID of essential oil extracts. The analyses showed a
      diversity of terpenoids. Of particular note were seven-member ring sesquiterpenes
      which were present in great abundance; a dendrogram showed clades separating by
      the production of bicyclogermacrene, aromadendrane and 5,10-cycloaromadendrane
      sesquiterpenoids for the four species. Comparison of volatile metabolite profiles
      to 13 other Vitex species showed strong similarities in the production of some
      monoterpenes, but varied by their production of larger terpenes, especially those
      with gem-dimethylcyclopropyl subunits on seven-member ring compounds. From this
      work, we suggest that the sesquiterpene skeleton with seven member rings is a
      good chemosystematic biomarker candidate for the Vitex genus. Separation using
      this biomarker was then validated using Inter-Simple Sequence Repeat profiling.
      Lastly, experiments examining the toxicity of these four oils against the coconut
      mite Aceria guerreronis showed that only the oil of V. gardneriana had strong
      acaricidal activity, with an LC50 of 0.85 mg/mL, thus demonstrating its potential
      for use as a natural pesticide.

PMID- 29184561
TI  - Characterization of a Thermo-Inducible Chlorophyll-Deficient Mutant in Barley.
AB  - Leaf color is an important trait for not only controlling crop yield but also
      monitoring plant status under temperature stress. In this study, a thermo
      inducible chlorophyll-deficient mutant, named V-V-Y, was identified from a gamma
      radiated population of the barley variety Vlamingh. The leaves of the mutant were
      green under normal growing temperature but turned yellowish under high
      temperature in the glasshouse experiment. The ratio of chlorophyll a and
      chlorophyll b in the mutant declined much faster in the first 7-9 days under heat
      treatment. The leaves of V-V-Y turned yellowish but took longer to senesce under
      heat stress in the field experiment. Genetic analysis indicated that a single
      nuclear gene controlled the mutant trait. The mutant gene (vvy) was mapped to the
      long arm of chromosome 4H between SNP markers 1_0269 and 1_1531 with a genetic
      distance of 2.2 cM and a physical interval of 9.85 Mb. A QTL for grain yield was
      mapped to the same interval and explained 10.4% of the yield variation with a LOD
      score of 4. This QTL is coincident with the vvy gene interval that is responsible
      for the thermo-inducible chlorophyll-deficient trait. Fine mapping, based on the
      barley reference genome sequence, further narrowed the vvy gene to a physical
      interval of 0.428 Mb with 11 annotated genes. This is the first report of fine
      mapping a thermo-inducible chlorophyll-deficient gene in barley.

PMID- 29184563
TI  - The Kinase ERULUS Controls Pollen Tube Targeting and Growth in Arabidopsis
      thaliana.
AB  - In this paper, we describe the role of the receptor-like kinase ERULUS (ERU) in
      PT growth of Arabidopsis thaliana. In silico analysis and transcriptional
      reporter lines revealed that ERU is only expressed in pollen and root hairs
      (RHs), making it a tip growth-specific kinase. Deviations from Mendelian
      inheritance were observed in the offspring of self-pollinated heterozygous eru
      plants. We found that in vivo eru PT targeting was disturbed, providing a
      possible explanation for the observed decrease in eru fertilization
      competitiveness. Extracellular calcium perception and intracellular calcium
      dynamics lie at the basis of in vivo pollen tube (PT) tip growth and guidance. In
      vitro, ERU loss-of-function lines displayed no obvious PT phenotype, unless grown
      on low extracellular calcium ([Ca2+]ext) medium. When grown at 12 the normal
      [Ca2+]ext, eru PTs grew 37% slower relative to WT PTs. Visualization of
      cytoplasmic [Ca2+]cyt oscillations using the Yellow Cameleon 3.6 (YC3.6) calcium
      sensor showed that, unlike in WT PTs, eru apical [Ca2+]cyt oscillations occur at
      a lower frequency when grown at lower [Ca2+]ext, consistent with the observed
      reduced growth velocity. Our results show that the tip growth-specific kinase
      ERULUS is involved in regulating Ca2+-dependent PT growth, and most importantly,
      fertilization efficiency through successful PT targeting to the ovules.

PMID- 29184562
TI  - De novo Transcriptome Assembly and Comparison of C3, C3-C4, and C4 Species of
      Tribe Salsoleae (Chenopodiaceae).
AB  - C4 photosynthesis is a carbon-concentrating mechanism that evolved independently
      more than 60 times in a wide range of angiosperm lineages. Among other
      alterations, the evolution of C4 from ancestral C3 photosynthesis requires
      changes in the expression of a vast number of genes. Differential gene expression
      analyses between closely related C3 and C4 species have significantly increased
      our understanding of C4 functioning and evolution. In Chenopodiaceae, a family
      that is rich in C4 origins and photosynthetic types, the anatomy, physiology and
      phylogeny of C4, C2, and C3 species of Salsoleae has been studied in great
      detail, which facilitated the choice of six samples of five representative
      species with different photosynthetic types for transcriptome comparisons. mRNA
      from assimilating organs of each species was sequenced in triplicates, and
      sequence reads were de novo assembled. These novel genetic resources were then
      analyzed to provide a better understanding of differential gene expression
      between C3, C2 and C4 species. All three analyzed C4 species belong to the NADP
      ME type as most genes encoding core enzymes of this C4 cycle are highly
      expressed. The abundance of photorespiratory transcripts is decreased compared to
      the C3 and C2 species. Like in other C4 lineages of Caryophyllales, our results
      suggest that PEPC1 is the C4-specific isoform in Salsoleae. Two recently
      identified transporters from the PHT4 protein family may not only be related to
      the C4 syndrome, but also active in C2 photosynthesis in Salsoleae. In the two
      populations of the C2 species S. divaricata transcript abundance of several C4
      genes are slightly increased, however, a C4 cycle is not detectable in the carbon
      isotope values. Most of the core enzymes of photorespiration are highly increased
      in the C2 species compared to both C3 and C4 species, confirming a successful
      establishment of the C2 photosynthetic pathway. Furthermore, a function of PEP-CK
      in C2 photosynthesis appears likely, since PEP-CK gene expression is not only
      increased in S. divaricata but also in C2 species of other groups.

PMID- 29184564
TI  - The Molybdenum Cofactor Biosynthesis Network: In vivo Protein-Protein
      Interactions of an Actin Associated Multi-Protein Complex.
AB  - Survival of plants and nearly all organisms depends on the pterin based
      molybdenum cofactor (Moco) as well as its effective biosynthesis and insertion
      into apo-enzymes. To this end, both the central Moco biosynthesis enzymes are
      characterized and the conserved four-step reaction pathway for Moco biosynthesis
      is well-understood. However, protection mechanisms to prevent degradation during
      biosynthesis as well as transfer of the highly oxygen sensitive Moco and its
      intermediates are not fully enlightened. The formation of protein complexes
      involving transient protein-protein interactions is an efficient strategy for
      protected metabolic channelling of sensitive molecules. In this review, Moco
      biosynthesis and allocation network is presented and discussed. This network was
      intensively studied based on two in vivo interaction methods: bimolecular
      fluorescence complementation (BiFC) and split-luciferase. Whereas BiFC allows
      localisation of interacting partners, split-luciferase assay determines
      interaction strengths in vivo. Results demonstrate (i) interaction of Cnx2 and
      Cnx3 within the mitochondria and (ii) assembly of a biosynthesis complex
      including the cytosolic enzymes Cnx5, Cnx6, Cnx7, and Cnx1, which enables a
      protected transfer of intermediates. The whole complex is associated with actin
      filaments via Cnx1 as anchor protein. After biosynthesis, Moco needs to be handed
      over to the specific apo-enzymes. A potential pathway was discovered. Molybdenum
      containing enzymes of the sulphite oxidase family interact directly with Cnx1. In
      contrast, the xanthine oxidoreductase family acquires Moco indirectly via a Moco
      binding protein (MoBP2) and Moco sulphurase ABA3. In summary, the uncovered
      interaction matrix enables an efficient transfer for intermediate and product
      protection via micro-compartmentation.

PMID- 29184565
TI  - A Novel QTL for Powdery Mildew Resistance in Nordic Spring Barley (Hordeum
      vulgare L. ssp. vulgare) Revealed by Genome-Wide Association Study.
AB  - The powdery mildew fungus, Blumeria graminis f. sp. hordei is a worldwide threat
      to barley (Hordeum vulgare L. ssp. vulgare) production. One way to control the
      disease is by the development and deployment of resistant cultivars. A genome
      wide association study was performed in a Nordic spring barley panel consisting
      of 169 genotypes, to identify marker-trait associations significant for powdery
      mildew. Powdery mildew was scored during three years (2012-2014) in four
      different locations within the Nordic region. There were strong correlations
      between data from all locations and years. In total four QTLs were identified,
      one located on chromosome 4H in the same region as the previously identified mlo
      locus and three on chromosome 6H. Out of these three QTLs identified on
      chromosome 6H, two are in the same region as previously reported QTLs for powdery
      mildew resistance, whereas one QTL appears to be novel. The top NCBI BLASTn hit
      of the SNP markers within the novel QTL predicted the responsible gene to be the
      26S proteasome regulatory subunit, RPN1, which is required for innate immunity
      and powdery mildew-induced cell death in Arabidopsis. The results from this study
      have revealed SNP marker candidates that can be exploited for use in marker
      assisted selection and stacking of genes for powdery mildew resistance in barley.

PMID- 29184566
TI  - Selection Signatures in the First Exon of Paralogous Receptor Kinase Genes from
      the Sym2 Region of the Pisum sativum L. Genome.
AB  - During the initial step of the symbiosis between legumes (Fabaceae) and nitrogen
      fixing bacteria (rhizobia), the bacterial signal molecule known as the Nod factor
      (nodulation factor) is recognized by plant LysM motif-containing receptor-like
      kinases (LysM-RLKs). The fifth chromosome of barrel medic (Medicago truncatula
      Gaertn.) contains a cluster of paralogous LysM-RLK genes, one of which is known
      to participate in symbiosis. In the syntenic region of the pea (Pisum sativum L.)
      genome, three genes have been identified: PsK1 and PsSym37, two symbiosis-related
      LysM-RLK genes with known sequences, and the unsequenced PsSym2 gene which
      presumably encodes a LysM-RLK and is associated with increased selectivity to
      certain Nod factors. In this work, we identified a new gene encoding a LysM-RLK,
      designated as PsLykX, within the Sym2 genomic region. We sequenced the first
      exons (corresponding to the protein receptor domain) of PsSym37, PsK1, and PsLykX
      from a large set of pea genotypes of diverse origin. The nucleotide diversity of
      these fragments was estimated and groups of haplotypes for each gene were
      revealed. Footprints of selection pressure were detected via comparative analyses
      of SNP distribution across the first exons of these genes and their homologs
      MtLYK2, MtLYK3, and MtLYK4 from M. truncatula retrieved from the Medicago Hapmap
      project. Despite the remarkable similarity among all the studied genes, they
      exhibited contrasting selection signatures, possibly pointing to diversification
      of their functions. Signatures of balancing selection were found in LysM1
      encoding parts of PsSym37 and PsK1, suggesting that the diversity of these parts
      may be important for pea LysM-RLKs. The first exons of PsSym37 and PsK1 displayed
      signatures of purifying selection, as well as MtLYK2 of M. truncatula. Evidence
      of positive selection affecting primarily LysM domains was found in all three
      investigated M. truncatula genes, as well as in the pea gene PsLykX. The data
      suggested that PsLykX is a promising candidate for PsSym2, which has remained
      elusive for more than 30 years.

PMID- 29184567
TI  - Ecological Factors Affecting Infection Risk and Population Genetic Diversity of a
      Novel Potyvirus in Its Native Wild Ecosystem.
AB  - Increasing evidence indicates that there is ample diversity of plant virus
      species in wild ecosystems. The vast majority of this diversity, however, remains
      uncharacterized. Moreover, in these ecosystems the factors affecting plant virus
      infection risk and population genetic diversity, two traits intrinsically linked
      to virus emergence, are largely unknown. Along 3 years, we have analyzed the
      prevalence and diversity of plant virus species from the genus Potyvirus in
      evergreen oak forests of the Iberian Peninsula, the main wild ecosystem in this
      geographic region and in the entire Mediterranean basin. During this period, we
      have also measured plant species diversity, host density, plant biomass,
      temperature, relative humidity, and rainfall. Results indicated that potyviruses
      were always present in evergreen oak forests, with a novel virus species
      explaining the largest fraction of potyvirus-infected plants. We determined the
      genomic sequence of this novel virus and we explored its host range in natural
      and greenhouse conditions. Natural host range was limited to the perennial plant
      mountain rue (Ruta montana), commonly found in evergreen oak forests of the
      Iberian Peninsula. In this host, the virus was highly prevalent and was therefore
      provisionally named mediterranean ruda virus (MeRV). Focusing in this natural
      host-virus interaction, we analyzed the ecological factors affecting MeRV
      infection risk and population genetic diversity in its native wild ecosystem. The
      main predictor of virus infection risk was the host density. MeRV prevalence was
      the major factor determining genetic diversity and selection pressures in the
      virus populations. This observation supports theoretical predictions assigning
      these two traits a key role in parasite epidemiology and evolution. Thus, our
      analyses contribute both to characterize viral diversity and to understand the
      ecological determinants of virus population dynamics in wild ecosystems.

PMID- 29184568
TI  - Metabolic Origins and Transport of Vitamin E Biosynthetic Precursors.
AB  - Tocochromanols are organic compounds mostly produced by photosynthetic organisms
      that exhibit vitamin E activity in animals. They result from the condensation of
      homogentisate with four different polyprenyl side chains derived all from
      geranylgeranyl pyrophosphate. The core tocochromanol biosynthesis has been
      investigated in several photosynthetic organisms and is now well-characterized.
      In contrast, our current knowledge of the biosynthesis and transport of
      tocochromanol biosynthetic precursors is much more limited. While tocochromanol
      synthesis occurs in plastids, converging genetic data in Arabidopsis and soybean
      demonstrate that the synthesis of the polar precursor homogentisate is located in
      the cytoplasm. These data implies that tocochromanol synthesis involves several
      plastidic membrane transporter(s) that remain to be identified. In addition, the
      metabolic origin of the lipophilic isoprenoid precursor is not fully elucidated.
      While some genetic data exclusively attribute the synthesis of the prenyl
      component of tocochromanols to the plastidic methyl erythritol phosphate pathway,
      multiple lines of evidence provided by feeding experiments and metabolic
      engineering studies indicate that it might partially originate from the
      cytoplasmic mevalonate pathway. Although this question is still open, these data
      demonstrate the existence of membrane transporter(s) capable of importing
      cytosolic polyprenyl pyrophosphate such as farnesyl pyrophosphate into plastids.
      Since the availability of both homogentisate and polyprenyl pyrophosphates are
      currently accepted as major mechanisms controlling the type and amount of
      tocochromanols produced in plant tissues, we summarized our current knowledge and
      research gaps concerning the biosynthesis, metabolic origins and transport of
      tocochromanol biosynthetic precursors in plant cells.

PMID- 29184570
TI  - Opium, an important risk factor for deep vein thrombosis patients.

PMID- 29184569
TI  - The Seed Repair Response during Germination: Disclosing Correlations between DNA
      Repair, Antioxidant Response, and Chromatin Remodeling in Medicago truncatula.
AB  - This work provides novel insights into the effects caused by the histone
      deacetylase inhibitor trichostatin A (TSA) during Medicago truncatula seed
      germination, with emphasis on the seed repair response. Seeds treated with H2O
      and TSA (10 and 20 MUM) were collected during imbibition (8 h) and at the radicle
      protrusion phase. Biometric data showed delayed germination and impaired seedling
      growth in TSA-treated samples. Comet assay, performed on radicles at the
      protrusion phase and 4-days old M. truncatula seedlings, revealed accumulation of
      DNA strand breaks upon exposure to TSA. Activation of DNA repair toward TSA
      mediated genotoxic damage was evidenced by the up-regulation of MtOGG1(8
      OXOGUANINE GLYCOSYLASE/LYASE) gene involved in the removal of oxidative DNA
      lesions, MtLIGIV(LIGASE IV) gene, a key determinant of seed quality, required for
      the rejoining of DNA double strand breaks and TDP(TYROSYL-DNA PHOSPHODIESTERASE)
      genes encoding the multipurpose DNA repair enzymes tyrosyl-DNA
      phosphodiesterases. Since radical scavenging can prevent DNA damage, the specific
      antioxidant activity (SAA) was measured by DPPH (1,1-diphenyl-2-picrylhydrazyl)
      and Folin-Ciocalteu reagent assays. Fluctuations of SAA were observed in TSA
      treated seeds/seedlings concomitant with the up-regulation of antioxidant genes
      MtSOD(SUPEROXIDE DISMUTASE, MtAPX(ASCORBATE PEROXIDASE) and MtMT2(TYPE 2
      METALLOTHIONEIN). Chromatin remodeling, required to facilitate the access of DNA
      repair enzymes at the damaged sites, is also part of the multifaceted seed repair
      response. To address this aspect, still poorly explored in plants, the
      MtTRRAP(TRANSFORMATION/TRANSACTIVATION DOMAIN-ASSOCIATED PROTEIN) gene was
      analyzed. TRRAP is a transcriptional adaptor, so far characterized only in human
      cells where it is needed for the recruitment of histone acetyltransferase
      complexes to chromatin during DNA repair. The MtTRRAP gene and the predicted
      interacting partners MtHAM2 (HISTONE ACETYLTRANSFERASE OF THE MYST FAMILY) and
      MtADA2A (TRANSCRIPTIONAL ADAPTOR) showed tissue- and dose-dependent fluctuations
      in transcript levels. PCA (Principal Component Analysis) and correlation analyses
      suggest for a new putative link between DNA repair and chromatin remodeling that
      involves MtOGG1 and MtTRRAP genes, in the context of seed germination.
      Interesting correlations also connect DNA repair and chromatin remodeling with
      antioxidant players and proliferation markers.

PMID- 29184571
TI  - Myocardial bridge over the left anterior descending coronary artery: A case
      report and review of the literature.
AB  - Myocardial bridging (MB) is considered as a topic of high interest since its
      occurrence in different studies is statistically significant, and the clinical
      manifestations of this phenomenon are complicated with cardiovascular diseases.
      Whether the MB participates in heart diseases and has a decisive effect to life
      threatening situations is still under research, and many studies have been
      conducted to clarify the abovementioned question. A case report with a MB on the
      left anterior descending coronary artery is presented in the current study, and a
      review of the literature is provided as well. Cardiologists as well thoracic
      surgeons and radiologists should bear in their mind the potential presence of
      such variant during interpretation of angiographies and multidetector-computed
      tomography.

PMID- 29184572
TI  - Compliance with continuous positive airway pressure in Persian patients with
      obstructive sleep apnea.
AB  - Background: Obstructive sleep apnea (OSA) is defined by recurrent apnea and
      hypopnea during sleep. The main treatment of OSA is continuous positive airway
      pressure (CPAP). Adherence to CPAP is challenging and depends on multiple
      factors. This study was designed to evaluate the compliance with CPAP in patients
      with OSA. Materials and Methods: This was a prospective observational study
      including 106 patients with confirmed OSA by a standard polysomnography. We
      recorded CPAP usage hours after 7 and 90 days by a smart card. We compared the
      adherence of the patients with respect to body mass index (BMI), gender, smoking
      status, living area, and education level. Results: Patients in the 18-45 years'
      age group had higher compliance in mean (standard deviation) daily use of CPAP
      (0.93 [0.40] h) compared to the other age groups (P < 0.001). Patients with BMI
      >35 had better compliance (1.13 [0.44]) than the other patients (P < 0.001).
      Furthermore, nonsmokers and highly educated patients had better compliance
      compared to the others (P < 0.001). Conclusion: Age, BMI, education, and smoking
      are important factors in adherence to CPAP in patients with OSA.

PMID- 29184573
TI  - Comparing of Cox model and parametric models in analysis of effective factors on
      event time of neuropathy in patients with type 2 diabetes.
AB  - Background: Cox proportional hazard model is the most common method for analyzing
      the effects of several variables on survival time. However, under certain
      circumstances, parametric models give more precise estimates to analyze survival
      data than Cox. The purpose of this study was to investigate the comparative
      performance of Cox and parametric models in a survival analysis of factors
      affecting the event time of neuropathy in patients with type 2 diabetes.
      Materials and Methods: This study included 371 patients with type 2 diabetes
      without neuropathy who were registered at Fereydunshahr diabetes clinic. Subjects
      were followed up for the development of neuropathy between 2006 to March 2016. To
      investigate the factors influencing the event time of neuropathy, significant
      variables in univariate model (P < 0.20) were entered into the multivariate Cox
      and parametric models (P < 0.05). In addition, Akaike information criterion (AIC)
      and area under ROC curves were used to evaluate the relative goodness of fitted
      model and the efficiency of each procedure, respectively. Statistical computing
      was performed using R software version 3.2.3 (UNIX platforms, Windows and MacOS).
      Results: Using Kaplan-Meier, survival time of neuropathy was computed 76.6 +/- 5
      months after initial diagnosis of diabetes. After multivariate analysis of Cox
      and parametric models, ethnicity, high-density lipoprotein and family history of
      diabetes were identified as predictors of event time of neuropathy (P < 0.05).
      Conclusion: According to AIC, "log-normal" model with the lowest Akaike's was the
      best-fitted model among Cox and parametric models. According to the results of
      comparison of survival receiver operating characteristics curves, log-normal
      model was considered as the most efficient and fitted model.

PMID- 29184574
TI  - Evaluation of response to hepatitis B vaccine in Iranian 6-18-year-old students.
AB  - Background: Hepatitis B is a dangerous disease with high morbidity and mortality
      rates all around the world. Vaccination is the most important way to its
      prevention and control. This cross-sectional study was carried out to study the
      levels of immunogenicity to hepatitis B vaccine in students. Materials and
      Methods: Six hundred and forty-four students aged 6-18 years including 316 girls
      and 328 boys were selected from the Chaharmahal Va Bakhtiari province. Selected
      students had been received three doses of recombinant vaccine (0, 1, and 6
      months). Blood samples were taken and the titers of hepatitis B surface antigen
      were studied. Results: From a total of 644 students, 396 (61.5%) had a titer
      lesser than 10 mIu/ml and 248 (38.5%) had a titer higher than 10 mIu/ml.
      Therefore, the level of respond to vaccine with 95% confidence was 38.5% (34.7%
      42.4%). Levels of respond to vaccine were related to age, body mass index (BMI),
      and educational level and were not related to sex and habit of students.
      Conclusion: Reverse significant relation was seen between the respond to vaccine
      and age and BMI in a way which the titers of antibody were lower in students with
      higher age and BMI.

PMID- 29184575
TI  - Acquired tumor resistance to antiangiogenic therapy: Mechanisms at a glance.
AB  - Angiogenesis is critical for oxygen and nutrient delivery to proliferating tumor
      cells. Therefore, as angiogenesis is required and vital for the tumor growth and
      metastasis. Antiangiogenic therapy is considered to be beneficial for tumor
      growth prevention due to starvation of tumor of oxygen and nutrients, but in some
      cases, the benefits are not permanent. Tyrosine kinase inhibitors and many other
      agents often target angiogenesis through inhibition of the vascular endothelial
      growth factor (VEGF) pathway. Although preclinical studies showed satisfactory
      outcomes in tumor growth inhibition, antiangiogenic therapy in the clinical
      setting may not be effective. The resistance observed in several tumor types
      through alternative angiogenic "escape" pathways contributes to restoration of
      tumor growth and may induce progression, enhancement of invasion, and metastasis.
      Therefore, activation of major compensatory angiogenic pathways, sustaining tumor
      angiogenesis during VEGF blockade contributing to the recurrence of tumor growth
      overcome antiangiogenic strategies. In this review, we summarize the novel
      mechanisms involved in evasive resistance to antiangiogenic therapies and
      represent different cancer types which have the ability to adapt to VEGF
      inhibition achieving resistance to antiangiogenic therapy through these adaptive
      mechanisms.

PMID- 29184577
TI  - Does zinc possess renoprotective properties in patients under cardiac surgery?

PMID- 29184576
TI  - The relationship between food insecurity with cardiovascular risk markers and
      metabolic syndrome components in patients with diabetes: A population-based study
      from Kerman coronary artery disease risk study.
AB  - Background: We sought the prevalence of food insecurity and whether
      cardiovascular risk markers and metabolic syndrome components are significantly
      different in categories of food insecurity in patients with type 2 diabetes.
      Materials and Methods: In this cross-sectional study, 520 patients with type 2
      diabetes from the Kerman coronary artery disease risk study aged between 23 and
      87 years (60.8 +/- 11.4) who selected by one-stage cluster sampling were assigned
      into four groups of "food secure" and "mild," "moderate," and "severe" food
      insecure. Household food insecurity was assessed by a 9-item household food
      insecurity access scale questionnaire. Results: The prevalence of food security
      and mild, moderate, and severe food insecurity in patients with diabetes was
      24.4%, 33.1%, 28.9%, and 13.6%, respectively. There was a significant difference
      among the food-secure/insecure sex groups (P = 0.001). The prevalence of food
      insecurity and risk factors such as total cholesterol, high low-density
      lipoprotein cholesterol, and visceral obesity in mild food-insecure females was
      significantly higher than males (P < 0.001, 0.001, and 0.001, respectively). The
      fasting blood sugar significantly increased (P = 0.020) in diabetic females with
      food security than the other female groups. Diastolic blood pressure
      significantly increased (P = 0.028) in diabetic females with severe food
      insecurity than the other female groups. The glycosylated hemoglobin
      significantly increased (P = 0.013) in diabetic males with severe food insecurity
      than the other male groups. Food insecurity odds ratio in females was 1.74 (95%
      confidence interval [CI]: 1.10-2.70), 2.39 (95% CI: 1.48-3.88), and 2.73 (95% CI:
      1.49-5.01) times higher than in males for mild, moderate, and severe food
      insecurity, respectively. Conclusion: Food insecurity may deteriorate some
      cardiometabolic biomarkers in type 2 diabetes. Improving food security in
      patients with diabetes may help reduce cardiovascular disease.

PMID- 29184578
TI  - The Effect of Emotional Intelligence Training on Self-efficacy in Women with
      Multiple Sclerosis.
AB  - Background: Multiple sclerosis (MS), a chronic disease of the central nervous
      system (CNS), causing progressive nerve damage, has disabling symptoms, and
      undermines self-efficacy beliefs. Due to the importance of self-efficacy modified
      in adaptation and coping with stress, this study was conducted with the aim to
      investigate the effect of emotional intelligence training on self-efficacy in
      women with MS. Materials and Methods: This randomized clinical trial was
      conducted on 70 women referring to the Multiple Sclerosis Clinic of Kashani
      Hospital, Isfahan, Iran. The participants were randomly assigned to two groups
      through minimization method. In the experimental group, emotional intelligence
      training was performed within 8 weeks, once a week for 90 minutes, in groups of 8
      9 individuals. Data were collected using the Multiple Sclerosis Self-efficacy
      Scale (MSSS) before, immediately after, and 3 months after the intervention in
      both groups. Data were analyzed using independent t-test and repeated measures
      ANOVA in SPSS. Results: The results of independent t-test showed no significant
      difference between the groups in terms of mean self-efficacy scores before the
      intervention (p > 0.05). However, there was a significant difference between the
      groups in this regard immediately after and 3 months after the intervention (p <
      0.05). Repeated measures ANOVA showed a significant difference in the mean score
      of self-efficacy and its components between the groups at different times (p <
      0.05). Conclusions: It seems that emotional intelligence training is effective on
      the improvement of self-efficacy of women with MS. Hence, this method can be
      recommended as an effective and affordable technique.

PMID- 29184579
TI  - The Impact of Peer Support Program on Adherence to the Treatment Regimen in
      Patients with Hypertension: A Randomized Clinical Trial Study.
AB  - Background: High blood pressure is the greatest risk factor of death, and
      patients should manage to control it. Peer support program is used to control
      chronic diseases. This study aims to determine the effect of peer support program
      on adherence to the regimen in patients suffering from hypertension. Materials
      and Methods: This study is a clinical trial conducted among 64 patients with
      hypertension referring to the Hypertension Research Center (Isfahan. Iran). The
      information was collected in three stages - before the start of intervention,
      immediately after, and 1 month after the intervention using a questionnaire of
      adherence to the treatment regimen for high blood pressure. The questionnaires
      were filled using a questioning method by patients who were not aware of the
      study. The experimental group attended 6 sessions of the peer support program (1
      hour), and the control group attended two sessions held by the researcher. Data
      were analyzed using the Statistical Package for the Social Sciences version 18
      software, and statistical tests were analyzed using independent t-test and
      analysis of variance with repeated measures. Results: Before the intervention,
      there was no significant difference in adherence to the treatment regimen score
      between the two groups regarding the three aspects of medication regimen, diet,
      and activity program. Increase in scores of control group immediately after and 1
      month after peer support program was higher (p < 0.001) compared to before the
      intervention. Conclusions: This study showed that peer support programs had a
      positive impact on adherence to the treatment regimen in patients suffering from
      hypertension.

PMID- 29184580
TI  - The Impact of an Interactive Computer Game on the Quality of Life of Children
      Undergoing Chemotherapy.
AB  - Background: Quality of life (QOL) of children with cancer reduces right from the
      diagnosis of disease and the start of treatment. Computer games in medicine are
      utilized to interact with patients and to improve their health-related behaviors.
      This study aimed to investigate the effect of an interactive computer game on the
      QOL of children undergoing chemotherapy. Materials and Methods: In this clinical
      trial, 64 children with cancer aged between 8 and12 years were selected through
      convenience sampling and randomly assigned to experimental or control group. The
      experimental group played a computer game for 3 hours a week for 4 consecutive
      weeks and the control group only received routine care. The data collection tool
      was the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module Child self
      report designed for children aged between 8 to 12 years. Data were analyzed using
      descriptive and inferential statistics in SPSS software. Results: Before
      intervention, there was no significant difference between the two groups in terms
      of mean total QOL score (p = 0.87). However, immediately after the intervention
      (p = 0.02) and 1 month after the intervention (p < 0.001), the overall mean QOL
      score was significantly higher in the intervention group than the control group.
      Conclusions: Based on the findings, computer games seem to be effective as a tool
      in influencing health-related behavior and improving the QOL of children
      undergoing chemotherapy. Therefore, according to the findings of this study,
      computer games can be used to improve the QOL of children undergoing
      chemotherapy.

PMID- 29184581
TI  - Comparison of the Effect of Topical Application of Rosemary and Menthol for
      Musculoskeletal Pain in Hemodialysis Patients.
AB  - Background: Pain is the most common problem experienced by hemodialysis patients,
      especially musculoskeletal pain in lower extremities, which is usually not
      completely treated and adversely affects their quality of life. The present study
      was conducted with the aim to determine and compare the effects of topical
      application of menthol and rosemary for musculoskeletal pain in hemodialysis
      patients. Materials and Methods: The present single-blind clinical trial
      recruited 105 eligible patients undergoing hemodialysis in selected hospitals
      affiliated to Isfahan University of Medical Sciences; patients were selected by
      convenient sampling. Participants' severity of pain was determined prior to
      intervention. They were then randomly divided into rosemary, menthol, and placebo
      groups. All three groups applied medication on the site of pain on their legs
      three times a day for three days and recorded the severity of pain four hours
      after morning and afternoon applications. The statistical analysis of data was
      performed using SPSS 18. Results: The mean score of severity of pain before the
      intervention was not significantly different among the three groups (p = 0.83),
      but it became significantly different after intervention (p = 0.001). Significant
      differences were observed in mean severity of pain before and after intervention
      in rosemary and menthol groups (p < 0.001), but not in the placebo group (p =
      0.21). Conclusions: Topical application of menthol and rosemary can alleviate
      severity and frequency of recurrence of musculoskeletal pain in hemodialysis
      patients; however, according to the results of the study, none had precedence
      over the other.

PMID- 29184582
TI  - Challenges of Nurses' Empowerment in the Management of Patient Aggression: A
      Qualitative Study.
AB  - Background: Patients' aggression in the mental care setting is a global health
      problem with major psychological, physical, and economic consequences; nurse
      empowerment to manage this aggressive behavior is an important step in
      psychiatric nursing. The aim of this study was to explore psychiatric nurses'
      experiences of the challenges of empowerment in the management of patients'
      aggression. Materials and Methods: This qualitative study was performed among 20
      nurses working in a major referral psychiatric center in Iran during 2014-2016.
      The purposive sampling method was used for selecting the participants. Data were
      collected through semi-structured interviews, observations, and filed notes.
      Inductive content analysis was used for data analysis. Results: Three categories
      and ten subcategories were identified: inefficient organizational policy (limited
      human resources, mandatory shifts, shortage of protective equipment, lack of
      motivational sparks); insufficient job growth (failure to implement training
      programs, insufficient effort for job competence, lack of clinical guidelines);
      and deficiencies in the organizational culture (inadequate autonomy and
      authority, lack of the culture of prevention, culture of fault and blame after an
      incident). Conclusions: Psychiatric nurses were not satisfied with organizational
      empowering conditions for the management of patients' aggression and reported low
      levels of access to learning opportunity, receiving support and essential
      resources that led to unnecessary use of containment measures. Managers must make
      every effort to create organizational context that make it possible to empower
      nurses for optimal practice.

PMID- 29184583
TI  - A Qualitative Study on Negative Emotions Triggered by Breastfeeding; Describing
      the Phenomenon of Breastfeeding/Nursing Aversion and Agitation in Breastfeeding
      Mothers.
AB  - Background: Breastfeeding aversion and agitation (BAA) while breastfeeding is
      anecdotally known to occur in some women who breastfeed while pregnant or those
      who tandem feed a newborn and a toddler. However, it is a little-researched area
      and the paucity of published literature around BAA reveals a significant gap in
      the literature. Materials and Methods: This study presents the findings and
      responses of 694 women who filled in an anonymous survey questionnaire that
      collected data on their basic demographics and their experiences with
      breastfeeding. It uses thematic and inductive content analysis, with qualitative
      interpretive description to present the findings. Results: The findings of this
      study shed light on an experienced phenomenon of aversion and agitation whilst
      breastfeeding, which varies in form, severity, and duration. It is characterised
      by feelings of anger or rage, a skin crawling sensation and an urge to remove the
      suckling infant, but can also be feelings of agitation and irritability whilst
      the infant is latched. A number of mothers who experience aversion still continue
      to breastfeed, but have feelings of guilt and shame while also experiencing
      confusion around those feelings. Conclusions: BAA is a phenomenon that occurs in
      some women who breastfeed, whereby breastfeeding triggers negative emotions. The
      reason women experience it is not clearly known. Research is needed to understand
      its cause, triggers, and strategies to minimise the experience in breastfeeding
      mothers.

PMID- 29184584
TI  - Evaluating the Effective Factors for Reporting Medical Errors among Midwives
      Working at Teaching Hospitals Affiliated to Isfahan University of Medical
      Sciences.
AB  - Background: Recently, evaluation and accreditation system of hospitals has had a
      special emphasis on reporting malpractices and sharing errors or lessons learnt
      from errors, but still due to lack of promotion of systematic approach for
      solving problems from the same system, this issue has remained unattended. This
      study was conducted to determine the effective factors for reporting medical
      errors among midwives. Materials and Methods: This project was a descriptive
      cross-sectional observational study. Data gathering tools were a standard
      checklist and two researcher-made questionnaires. Sampling for this study was
      conducted from all the midwives who worked at teaching hospitals affiliated to
      Isfahan University of Medical Sciences through census method (convenient) and
      lasted for 3 months. Data were analyzed using descriptive and inferential
      statistics through SPSS 16. Results: Results showed that 79.1% of the staff
      reported errors and the highest rate of errors was in the process of patients'
      tests. In this study, the mean score of midwives' knowledge about the errors was
      79.1 and the mean score of their attitude toward reporting errors was 70.4. There
      was a direct relation between the score of errors' knowledge and attitude in the
      midwifery staff and reporting errors. Conclusions: Based on the results of this
      study about the appropriate knowledge and attitude of midwifery staff regarding
      errors and action toward reporting them, it is recommended to strengthen the
      system when it comes to errors and hospitals risks.

PMID- 29184585
TI  - Do Psychosocial Factors Predict Readmission among Diabetic Elderly Patients?
AB  - Background: Despite advances in diabetes treatment, the rate of readmission is
      still relatively high among these patients, especially in older population.
      Various factors may predict readmission in these patients; hence, the aim of this
      study was to assess the role of psychosocial factors in predicting readmission
      among diabetic elderly hospitalized in selected hospitals of Isfahan. Materials
      and Methods: In this cross-sectional study conducted from January to September
      2016, 150 diabetic elderly hospitalized in selected hospitals affiliated with
      Isfahan University of medical sciences were chosen using a convenient sampling
      method. The initial information was collected by a three-part questionnaire
      consisting of (a) demographic characteristics, (b) 21-item depression, anxiety,
      and stress scale (DASS-21), and (c) multidimensional scale of perceived social
      support (MSPSS). Further information about readmission was gathered 3 months
      after completing the questionnaires through a phone call follow-up. Descriptive
      and inferential statistics (discriminant function analysis test) were used to
      analyze the data. Results: During 3 months after discharge, 44% of hospitalized
      diabetic elderly were readmitted. Analytical model predicted the readmission
      status of 109 individuals (of total 150 persons) in the studied units (success
      rate of 72.2%). Among predicting factors, depression and social support had the
      most and the least important roles in predicting readmission rate, respectively.
      Conclusions: Interventions to improve mental status (i.e., decreasing levels of
      depression, anxiety, and stress) and develop social support are suggested to
      reduce the risk of readmission among diabetic elderly patients. Nevertheless,
      future studies are needed to verify the value of such interventions.

PMID- 29184586
TI  - Study of the Impact of Educational Behavioral Interventions on Fatigue in Mothers
      in the Postpartum Period in the Groups of Face-to-Face and Electronic Training.
AB  - Background: Maternal fatigue in the postpartum period include factors that affect
      the quality of life and health of both the mother and newborn. This study aimed
      to investigate two educational approaches regarding mother's fatigue in the
      postpartum period. Materials and Methods: This experimental study was performed
      among 110 pregnant mothers during their postpartum care using random sampling.
      The participants were divided in three groups, namely, face-to-face, e-learning,
      and control groups. Interventions included individual meetings between the
      researcher and mothers in the face-to-face group and giving educational compact
      disc to the e-learning department to improve maternal fatigue. Personal
      information and fertility data was obtained (before training); the maternal
      fatigue questionnaire Fatigue Severity Scale (FSS) was completed before and after
      any type of (face-to-face, e-learning, and control) education. Obtained data were
      analyzed using one-way analysis of variance (ANOVA) and repeated-measures ANOVA.
      Results: Results showed that both face-to-face and e-learning methods had similar
      maternal fatigue scores. The average change on the maternal fatigue score in the
      second treatment was (p = 0.02) and the third treatment was (p < 0.001)among
      three groups that was indicative of significant statistical differences.
      Similarly, there was no statistically significant difference in the average
      maternal fatigue score between the two groups before the intervention and in the
      second and third groups after the intervention. Therefore, over time, the
      training was unaffected. Conclusions: The findings of this study indicate that
      both face-to-face and e-learning methods are effective to reduce maternal
      postpartum fatigue.

PMID- 29184587
TI  - Assessment of the Relationship between Spiritual and Social Health and the Self
      Care Ability of Elderly People Referred to Community Health Centers.
AB  - Background: Promotion of self-care ability among older people is an essential
      means to help maintain and improve their health. However, the role of spiritual
      and social health has not yet been considered in detail in the context of self
      care ability among elderly. The aim of this study was to assess the relationship
      between spiritual and social health and self-care ability of older people
      referred to community health centers in Isfahan. Materials and Methods: In this
      cross-sectional correlation study, 200 people, aged 60 years and older, referred
      to healthcare centers in 2016 were recruited through convenience sampling method.
      Data were collected by four-part tool comprising of: (a) demographics, (b)
      Ellison and Palotzin's spiritual well-being scale, (c) Kees's "social health"
      scale, and (d) self-care ability scale for the elderly by Soderhamn's; data were
      analyzed by descriptive and inferential (independent t-test, analysis of variance
      - ANOVA, Pearson's coefficient tests, and multiple regression analysis)
      statistics by SPSS16 software. Results: Findings showed that the entered
      predictor variables were accounted for 41% of total variance (R2 ) of the two
      self-care ability in the model (p < 0.001, F3, 199 = 46.02). Two out of the three
      predictor variables including religious well-being and social health,
      significantly predicted the self-care ability of older people. Conclusions: The
      results of this study emphasized on the relationship between spiritual and social
      health of the elderly people and their ability to self-care. Therefore, it would
      be recommended to keep the focus of the service resources towards improving
      social and spiritual health to improve self-care ability in elderly people.

PMID- 29184588
TI  - Clinical Outcomes of High-Risk Infant Follow-Up Program in a Tertiary Care
      Centre.
AB  - Background: High-risk infant follow-up (HRIF) program is necessary for early
      detection, timely intervention, and promotion of health outcomes in vulnerable
      infants, ethically. The present study was carried out to assess the clinical
      outcomes of the HRIF Program in Alzahra hospital as a tertiary care centre, in
      Iran. Materials and Methods: In this cohort study, 5840 neonates were born at
      Alzahra hospital, from June 1, 2011 to 30th February 2012. Among those who were
      admitted to neonatal intensive care unit (NICU), 253 infants were recruited by
      census according to HRIs criteria. After doing necessary measurements and family
      education, information was recorded in HRI health certificate and then entered in
      the access database for analysis. Results: From 253 eligible HRIs registered, 241
      (95%) infants attended the follow-up clinic after discharge. A total of180 cases
      were recalled for further visits, 110 of which attended the clinic.
      Anthropometric indices had an increasing trend in the first 6 months of life.
      There was no significant relation between ages and stages questionnaire (ASQ)
      results and infant birth weight, height, and head circumference. The ratios of
      intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP) were 8.7%
      and 3.1%, respectively. The incidence of congenital hypothyroidism was 2:341 in
      HRIs. Conclusions: Although some outcomes, such as ROP, improved in our study
      compared to similar studies, the findings indicate an impairment of the current
      follow-up processes and highlight the necessity to modify the current HRIF
      program. Ethically, we insist on integrating HRIF program in child health
      services to promote early childhood development.

PMID- 29184589
TI  - Comparing the Effect of Echinacea and Chlorhexidine Mouthwash on the Microbial
      Flora of Intubated Patients Admitted to the Intensive Care Unit.
AB  - Background: Providing intubated patients admitted to the intensive care units
      with oral healthcare is one of the main tasks of nurses in order to prevent
      Ventilator-Associated Pneumonia (VAP). This study aimed at comparing the effects
      of two mouthwash solutions (echinacea and chlorhexidine) on the oral microbial
      flora of patients hospitalized in the intensive care units. Materials and
      Methods: In this clinical trial, 70 patients aged between18 and 65 years
      undergoing tracheal intubation through the mouth in three hospitals in Arak, were
      selected using simple random sampling and were randomly divided into two groups:
      the intervention group and the control group. The oral health checklist was used
      to collect the data (before and after the intervention). The samples were
      obtained from the orally intubated patients and were then cultured in selective
      media. Afterwards, the aerobic microbial growth was investigated in all culture
      media. The data were analyzed using SPSS software. Results: The microbial flora
      in the echinacea group significantly decreased after the intervention (p <
      0.0001) and it was also the case withmicrobial flora of the patients in the
      chlorhexidine group (p < 0.001). After 4 days, the oral microbial flora of the
      patients in the intervention group was lower than that of the patients in the
      control group (p < 0.001). Conclusions: The results showed that the echinacea
      solution was more effective in decreasing the oral microbial flora of patients in
      the intensive care unit. Given the benefits of the components of the herb
      Echinacea, it can be suggested as a viable alternative to chlorhexidine.

PMID- 29184590
TI  - The Impact of an Educational Program Regarding Total Parenteral Nutrition on
      Infection Indicators in Neonates Admitted to the Neonatal Intensive Care Unit.
AB  - Background: One of the basic care measures for preterm infants is providing
      nutrition through total parenteral nutrition (TPN) and one of the most important
      complications of it is infection. Because prevention of nosocomial infections is
      an important issue for neonate's safety, this study aimed to determine the
      effects of a continuing medical education (CME) course on TPN for neonatal
      intensive care unit (NICU) nurses on indicators of infection in newborns.
      Materials and Methods: This quasi-experimental study was conducted on 127
      neonates who fulfilled the inclusion criteria. They were selected through simple
      convenience sampling method at two stages of before and after the CME program.
      The inclusion criteria were prescription of TPN by the physician and lack of
      clinical evidences for infection in newborns before the beginning of TPN. Death
      of the infant during each stage of the study was considered as the exclusion
      criteria. The data gathering tool was a data record sheet including clinical
      signs of infection in the infants and their demographic characteristics. Data
      were analyzed using Chi-square test, Fisher's exact test, and student's t-test in
      SPSS software. Results: The results showed the frequency of clinical markers for
      infection in newborns at the pre-intervention stage (n = 41; 65.10%) was
      significantly less than at the post-intervention stage (n = 30; 46.90%) (p =
      0.04). Conclusions: Nursing educational programs on TPN reduce infection rates
      among neonates in NICUs.

PMID- 29184591
TI  - Iranian Pediatric Nurse's Experience: The Facilitators of the Learning of Ethical
      Practices.
AB  - Background: Ethical care is a core value in nursing. Pediatric nurses are in
      direct and continuous contact with children and their parents. They manage their
      lives and health. As part of the pediatric nurses' daily work, ethical issues
      play an important role in making decisions, are important to make decisions, and
      this capability is only achieved by ethical practice. This study aimed to explore
      the factors facilitating the learning of ethical practice among Iranian pediatric
      nurses. Materials and Methods: This study is a conventional qualitative content
      analysis based on the Graneheim and Lundman method. It was conducted through semi
      structured interviews with two focus groups, incorporating 28 nurses working in
      pediatric wards. Unstructured observation and field notes were other methods of
      data collection. Purposive sampling continued until data saturation was ensured.
      All interviews were tape recorded and transcribed in verbatim. Results: Three
      main categories and 12 subcategories emerged from this study. The facilitating
      factors include (1) individual competencies (knowledge, experience, emotional
      intelligence, and loving children), (2) ethical imprinting (responsibility,
      reflection, empathy, and ethical beliefs), and (3) an environment that nurtures
      moral values (organizational, spiritual, family, and cultural environments) as
      facilitating factors. Conclusions: The promotion of nurses' competencies, ethical
      virtues, and imprinting, as well as improvement of the quality of nursing care
      must be the top priority of the health team. Undoubtedly, the success of the
      health care system is not possible without ensuring that pediatric nurses learn
      ethical practices.

PMID- 29184592
TI  - An Interprofessional Education Pilot Study for Nursing and Speech-Language
      Pathology Students.
AB  - Background: Despite the complexity of patient care and promise of
      interprofessional collaboration in health professional educational programs,
      interprofessional education and practice implementation challenges exist.
      Materials and Methods: A pilot study with a nonequivalent comparison before/after
      design was conducted to examine undergraduate students' and graduate students'
      knowledge of the role of nurses and speech-language pathologists (SLPs) while
      working with patients diagnosed with dysphagia. All students received pre- and
      post-tests assessing their knowledge of the respective profession. Results: A
      repeated measure of analysis of variance using pre- and post-tests by group
      design revealed a strong and statistically significant main effect from pre- to
      post-testing, [F (1, 19) = 17.42, p = 0.001, and partial eta2= 0.48].
      Conclusions: The results indicated that students received higher scores on post
      tests. This study reinforces the importance of collaboration of healthcare
      professionals during their professional coursework.

PMID- 29184594
TI  - Severe fever and dyspnoea in a young girl with Hodgkin lymphoma.
AB  - Differential diagnosis of a young Hodgkin lymphoma patient with severe fever and
      dyspnoea http://ow.ly/p7N5306s0yW.

PMID- 29184593
TI  - Cognitive impairment in COPD: should cognitive evaluation be part of respiratory
      assessment?
AB  - : Cognitive impairment is highly prevalent in patients with COPD and demonstrates
      multiple detrimental effects on many aspects of patient state and therapeutic
      outcomes. It is attributed to several overlapping pathophysiological factors,
      with the most common being the low level of oxygen saturation due to respiratory
      insufficiency. Despite the impact of cognitive impairment on clinical outcomes,
      the screening for coexisting cognitive deficits which may interfere with the
      successful progress of respiratory treatment is yet neglected. There is a special
      consideration that cognitive deficits should be taken into account when
      developing respiratory therapy plans. Cognitively impaired patients are likely to
      require more support and have need of an individualised respiratory care plan
      which can also be beneficial for their cognitive deficits. Pulmonary
      rehabilitation as a multidisciplinary approach could be prioritised for COPD
      patients with cognitive impairment. Educational aims: To illustrate the common
      signs of cognitive impairment and define potential associations between lung and
      cognitive dysfunction.To illustrate the potential influence of cognitive deficits
      on the optimal progress of respiratory therapy.To illustrate the importance of
      cognitive evaluation as part of a comprehensive clinical assessment for patients
      suspected of suffering cognitive impairment.

PMID- 29184595
TI  - A 61-year-old male with generalised lymphadenopathy presenting with shortness of
      breath and infiltrates on chest radiography.
AB  - Can you diagnose this 61-year-old male with generalised lymphadenopathy, dyspnoea
      and radiographic infiltrates? http://ow.ly/AXDg306hfqo.

PMID- 29184596
TI  - The use of tracheal sounds for the diagnosis of sleep apnoea.
AB  - : Tracheal sounds have been the subject of many research studies. In this review,
      we describe the state of the art, original work relevant to upper airways
      obstruction during sleep, and ongoing research concerning the methods used when
      analysing tracheal sounds. Tracheal sound sensors are a simple and noninvasive
      means of measurement and are more reliable than other breathing sensors.
      Developments in acoustic processing techniques and enhancements in tracheal sound
      signals over the past decade have led to improvements in the accuracy and
      clinical relevance of diagnoses based on this technology. Past and current
      research suggests that they may have a significant role in the diagnosis of
      obstructive sleep apnoea. Key points: Tracheal sounds are currently a topic of
      significant interest but are not yet used in most routine sleep study
      systems.Measured at the suprasternal notch, tracheal sounds can provide reliable
      information on breathing sounds, snoring sounds and respiratory efforts.Tracheal
      sounds may be used as a noninvasive method of studying abnormalities of the upper
      airways during wakefulness. Educational aims: To understand the principles of
      tracheal sound measurement and analysis.To highlight the importance of tracheal
      sounds for the diagnosis of sleep apnoea-hypopnoea syndrome.To present the most
      relevant clinical studies that have validated the use of tracheal sound sensors
      and to make future clinical validation studies possible.

PMID- 29184597
TI  - The impact and cost-effectiveness of the Amref Health Africa-Smile Train Cleft
      Lip and Palate Surgical Repair Programme in Eastern and Central Africa.
AB  - Introduction: Cleft lip with or without cleft palate (CLP) is a congenital
      malformation that causes significant morbidity in low and middle income
      countries. Amref Health Africa has partnered with Smile Train to provide CLP
      surgeries since 2006. Methods: We analyzed anonymized data of 37,274 CLP patients
      from the Smile Train database operated on in eastern and central Africa between
      2006 and 2014. Cases were analyzed by age, gender, country and surgery type. The
      impact of cleft surgery was determined by measuring averted Disability-Adjusted
      Life Years (DALYs) and delayed averted DALYs. We used mean Smile Train costs to
      calculate cost-effectiveness. We calculated economic benefit using the human
      capital approach and Value of Statistical Life (VSL) methods. Results: The median
      age at time of primary surgery was 5.4 years. A total of 207,879 DALYs were
      averted at a total estimated cost of US$13 million. Mean averted DALYs per
      patient were 5.6, and mean cost per averted DALY was $62.8. Total delayed burden
      of disease from late age at surgery was 36,352 DALYs. Surgical correction
      resulted in $292 million in economic gain using the human capital approach and
      $2.4 billion using VSL methods. Conclusion: Cleft surgery is a cost-effective
      intervention to reduce disability and increase economic productivity in eastern
      and central Africa. Dedicated programs that provide essential CLP surgery can
      produce substantial clinical and economic benefits.

PMID- 29184598
TI  - [Exophytic tumor of the scalp].
AB  - Proliferating trichilemmal tumor (PTT), still referred to as proliferative
      trichilemmal cyst (TC), is an uncommon malignant adnexal tumor originating from
      the cells of the outer root sheath of the hair follicle or, more often, from a
      trichilemmal cyst, following multiple trauma and/or recurrent inflammation. We
      report the case of a 64-year old female patient, with no particular previous
      history, presenting with tumor of the scalp gradually evolving over 18 months.
      Clinical examination showed a painless, firm, adhering ulcero-budding tumor mass
      measuring 12 cm along its longer axis at the level of the vertex. The patient had
      clinically negative lymph nodes. Histological examination showed malpighian cell
      proliferation arranged in clumps and coalescing lobules with focal areas of
      abrupt trichilemmal keratinization, with very marked atypies cyto-nuclear and an
      infiltrated fibrous stroma, suggesting proliferating trichilemmal tumor. Staging
      evaluation showed no metastase. The patient underwent wide surgical resection
      followed by in depth removal of extra tissue, without recurrence at 3-months'
      follow-up.

PMID- 29184599
TI  - [Lipoma of the deep lobe of the parotid gland].
AB  - Lipomas of the parotid gland are benign tumors developing from the fatty tissue
      in the gland. They are rare, accounting for 0.6-4.4% of all benign tumors. Those
      located in the deep lobe of the gland are uncommon. Clinically, they are very
      difficult to diagnose. CT scan and especially MRI can support the diagnosis.
      Surgery is the treatment of choice but its modalities remain controversial. We
      report the case of a 52-year old female patient, with no particular past medical
      history, presenting with asymptomatic left preauricular mass evolving over 1 year
      and gradually increasing in volume. Clinical examination showed painless elastic
      swelling, measuring 2 * 1.5 * 1 cm, extending from the ear lobule to the left
      mandibular angle. Stensen duct wasn't obstructed and saliva was clear. The
      patient showed no facial paralysis. CT scan showed perfectly delimited unilobular
      hypodense homogeneous mass in the deep lobe of the parotid gland. No suspected
      cervical lymphadenopathy was detected. MRI confirmed the presence of homogeneous,
      lipomatous intraparotid tissue process. After superficial parotidectomy and
      translocation of the branches of the facial nerve, a yellowish mass appeared
      under the buccal and mandibular branches of the facial nerve. The patient
      underwent complete resection up to the left parapharyngeal space. The
      postoperative course was uneventful. Anatomo-pathological examination confirmed
      the diagnosis of lipoma of the deep lobe of the parotid gland.

PMID- 29184600
TI  - [Common variable immune deficiency lately revealed by gastrointestinal problems:
      about a case].
AB  - Common Variable Immune Deficiency (CVID) is rare. It is a constitutional deficit
      of humoral immunity characterized by recurrent bacterial infections and by
      increased frequency of tumors, autoimmune or granulomatous diseases.
      Gastrointestinal manifestations are very variable and sometimes reveal common
      variable immune deficiency. We report the case of a 31-year old patient with a
      history of childhood recurrent respiratory infections complicated by
      bronchiectasis and with a 3-year history of recurrent glairy diarrhea.
      Etiological balance was in favor of CVID with autoimmune manifestation
      (vitiligo). Patient's treatment was based on monthly immunoglobulin (Ig)
      infusions with favorable outcome at 2-year follow-up.

PMID- 29184601
TI  - Obesity as a form of malnutrition: over-nutrition on the Uganda "malnutrition"
      agenda.
AB  - : The objectives were to highlight the burden of overweight and obesity as an
      additional area of importance for the malnutrition agenda in Uganda and to
      provide evidence-based considerations for stakeholders involved. INTRODUCTION:
      Mirroring other Low- and Middle-Income Countries (LMICs), Uganda is experiencing
      a "double burden" of over-nutrition related issues - both obesity and overweight,
      and related non-communicable diseases (NCDs) alongside the under-nutrition that
      has long plagued the country. Despite the commonplace assumption that under
      nutrition is the predominant form of malnutrition in Uganda, we explore recent
      literature that in fact, challenges this notion. While food insecurity has
      contributed to the under-nutrition problem, a lack of dietary diversity also has
      a demonstrated role in increasing over-nutrition. We cannot afford to ignore over
      nutrition concomitant with stunting and wasting in the country. Increase in the
      burden of this less acknowledged form of malnutrition in Uganda is critical to
      investigate, and yet poorly understood. A move towards increased regionally
      targeted over-nutrition research, funding, government prioritization and advocacy
      is needed.

PMID- 29184602
TI  - [Giant lithiasis due to urinary stasis related to ileo-caecal bladder].
AB  - Bladder exstrophy is a malformation characterized by subumbilical anterior
      abdominal wall and anterior bladder wall deishence. It affects nearly 30.000
      40.000 births per year, with a higher prevalence in boys. External continent
      urinary diversion creates a long-term outcome. However, it is not devoid of
      complications. We report the case of a 30-year old female patient who had
      undergone cystectomy with bladder replaced with ileo-caecal segment for bladder
      exstrophy 13 years earlier. She was followed up for 5 years and then lost to
      follow up. In March 2017 she presented with painful abdominal heaviness as well
      as constipation evolving in a context of apyrexy and good general condition.
      Clinical examination showed good general health, midline laparotomy scar,
      continent uninvaginated urinary pouch valve. Pelvic examination was unremarkable.
      Hypogastric palpation showed nonpainful stony-hard mass. Urinary tract without
      preparation showed calcic opacity 130*110 mm as well as symphysis disjunction.
      Renal and pelvic ultrasound showed several hyperechogen images with posterior
      shadow cone occupying the pelvis, two well differentiated kidneys of normal size
      without ureteric hydronephrosis. CT urography showed 5 big calcium stones with an
      average density of 730 UH, the most voluminous of which measured 112*101 mm, in
      the neobladder. Renal function was normal and cytobacteriological examination of
      urine showed ESBL-producing E coli urinary tract infection sensitive to
      carbapenems. Treatment was based on suitable antibiotic therapy associated with
      entero-cystolithotomy involving laborious extraction of 5 big stones.
      Spectrophotometric examination revealed phospho-ammonium-magnesium stones. The
      postoperative course was uneventful, post operative urinary tract without
      preparation showed no stones.

PMID- 29184603
TI  - Lhermitte-Duclos disease: an extremely rare cerebellar tumor.

PMID- 29184604
TI  - Cyst of the back of the hand.

PMID- 29184605
TI  - The risk of ischemic optic neuropathy post phacoemulsification cataract surgery.
AB  - Introduction: The aim was to study the risk of non arteritic ischemic optic
      neuropathy after phacoemulsification cataract surgery. Methods: This study was
      conducted at King Hussein Medical Center during the period between January 2015
      and July 2016. Patients attending ophthalmology clinic complaining of decreased
      vision due to lens opacity were evaluated. Patients were divided into two groups.
      First group included patients with no medical illness and second group included
      patients with diabetes mellitus, hypertension or hyperlipidemia. The two groups
      were further divided into two subgroups. First subgroup included patients who had
      phacoemulsification surgery and second subgroup did not have surgery. All
      patients were followed up for 6 months. They were assessed by neuro
      ophthalmologist looking for ischemic optic neuropathy. Results: A total number of
      568 patients were enrolled. Group 1A included patients with no medical illness
      who underwent surgery and group 1B did not undergo surgery. The number of
      patients in these two subgroups was 119 and 103 respectively. Number of patients
      in group 2A (medical illness and surgery) was 188 and number of patients in group
      2B (medical illness and no surgery) was 130. The incidence of ischemic optic
      neuropathy was 4.3 % in group 2A, 4.2 % in group 1A, 0.8% in group 2B, and 0% in
      group 1B. Conclusion: Phacoemulsification is a risk factor for non arteritic
      ischemic optic neuropathy independent of the presence of medical risk factors.
      Suggested mechanisms would be local anaesthesia, intraocular pressure fluctuation
      and local intraocular inflammation.

PMID- 29184606
TI  - Knowledge, attitude and practice of hygiene and sanitation in a Burundian refugee
      camp: implications for control of a Salmonella typhi outbreak.
AB  - Introduction: A Salmonella typhi outbreak was reported in a Burundian refugee
      camp in Rwanda in October 2015. Transmission persisted despite increased hygiene
      promotion activities and hand-washing facilities instituted to prevent and
      control the outbreak. A knowledge, attitude and practice (KAP) study was carried
      out to assess the effectiveness of ongoing typhoid fever preventive
      interventions. Methods: A cross-sectional survey was conducted in Mahama Refugee
      Camp of Kirehe District, Rwanda from January to February 2016. Data were obtained
      through administration of a structured KAP questionnaire. Descriptive, bivariate
      and multivariate analysis was performed using STATA software. Results: A total of
      671 respondents comprising 264 (39.3%) males and 407 (60.7%) females were
      enrolled in the study. A comparison of hand washing practices before and after
      institution of prevention and control measures showed a 37% increase in the
      proportion of respondents who washed their hands before eating and after using
      the toilet (p < 0.001). About 52.8% of participants reported having heard about
      typhoid fever, however 25.9% had received health education. Only 34.6% and 38.6%
      of the respondents respectively knew how typhoid fever spreads and is prevented.
      Most respondents (98.2%) used pit latrines for disposal of feces. Long duration
      of stay in the camp, age over 35 years and being unemployed were statistically
      associated with poor hand washing practices. Conclusion: The findings of this
      study underline the need for bolstering up health education and hygiene promotion
      activities in Mahama and other refugee camp settings.

PMID- 29184607
TI  - [Unilateral macular coloboma: about a case].
AB  - Macular coloboma is a congenital condition characterized by failure of closure of
      the fetal intraocular fissure which may have a hereditary origin. Clinically, it
      is characterized by decreased visual acuity with macular excavated lesion
      characterized by missing or rudimentary retinal tissue and scleral ectasia.
      Macular OCT strongly supports the diagnosis and electrophysiology examination, if
      requested, is altered. Differential diagnosis includes pathologies causing
      atrophic and excavated macular lesion, in particular congenital toxoplasmosis.

PMID- 29184610
TI  - Colonoscopy procedural volume increases adenoma and polyp detection rates in
      gastroenterologytrainees.
AB  - AIM: To investigate changes in polyp detection throughout fellowship training,
      and estimate colonoscopy volume required to achieve the adenoma detection rate
      (ADRs) and polyp detection rate (PDRs) of attending gastroenterologists. METHODS:
      We reviewed colonoscopies from July 1, 2009 to June 30, 2014. Fellows' procedural
      logs were used to retrieve colonoscopy procedural volumes, and these were treated
      as the time variable. Findings from screening colonoscopies were used to
      calculate colonoscopy outcomes for each fellow for the prior 50 colonoscopies at
      each time point. ADR and PDR were plotted against colonoscopy procedural volumes
      to produce individual longitudinal graphs. Repeated measures linear mixed effects
      models were used to study the change of ADR and PDR with increasing procedural
      volume. RESULTS: During the study period, 12 fellows completed full three years
      of training and were included in the analysis. The average ADR and PDR were,
      respectively, 31.5% and 41.9% for all fellows, and 28.9% and 38.2% for attendings
      alone. There was a statistically significant increase in ADR with increasing
      procedural volume (1.8%/100 colonoscopies, P = 0.002). Similarly, PDR increased
      2.8%/100 colonoscopies (P = 0.0001), while there was no significant change in
      advanced ADR (0.04%/100 colonoscopies, P = 0.92). The ADR increase was limited to
      the right side of the colon, while the PDR increased in both the right and left
      colon. The adenoma per colon and polyp per colon also increased throughout
      training. Fellows reached the attendings' ADR and PDR after 265 and 292
      colonoscopies, respectively. CONCLUSION: We found that the ADR and PDR increase
      with increasing colonoscopy volume throughout fellowship. Our findings support
      recent recommendations of >= 275 colonoscopies for colonoscopy credentialing.

PMID- 29184609
TI  - Liver atrophy after percutaneous transhepatic portal embolization occurs in two
      histological phases: Hepatocellular atrophy followed by apoptosis.
AB  - AIM: To clarify the histological changes associated with liver atrophy after
      percutaneous transhepatic portal embolization (PTPE) in pigs and humans. METHODS:
      As a preliminary study, we performed pathological examinations of liver specimens
      from five pigs that had undergone PTPE in a time-dependent model of liver
      atrophy. In specimens from embolized lobes (EMB) and nonembolized lobes
      (controls), we measured the portal vein to central vein distance (PV-CV), the
      area and number of hepatocytes per lobule, and apoptotic activity using the
      terminal deoxynucleotidyl transferase dUTP nick-end labeling assay.
      Immunohistochemical reactivities were evaluated for light chain 3 (LC3) and
      lysosomal-associated membrane protein 2 (LAMP2) as autophagy markers and for
      glutamine synthetase and cytochrome P450 2E1 (CYP2E1) as metabolic zonation
      markers. Samples from ten human livers taken 20-36 d after PTPE were similarly
      examined. RESULTS: PV-CVs and lobule areas did not differ between EMB and
      controls at day 0, but were lower in EMB than in controls at weeks 2, 4, and 6 (P
      <= 0.001). Hepatocyte numbers were not significantly reduced in EMB at day 0 and
      week 2 but were reduced at weeks 4 and 6 (P <= 0.05). Apoptotic activity was
      higher in EMB than in controls at day 0 and week 4. LC3 and LAMP2 staining peaked
      in EMB at week 2, with no significant difference between EMB and controls at
      weeks 4 and 6. Glutamine synthetase and CYP2E1 zonation in EMB at weeks 2, 4, and
      6 were narrower than those in controls. Human results were consistent with those
      of porcine specimens. CONCLUSION: The mechanism of liver atrophy after PTPE has
      two histological phases: Hepatocellular atrophy is likely caused by autophagy in
      the first 2 wk and apoptosis thereafter.

PMID- 29184608
TI  - Role of pregnane X-receptor in regulating bacterial translocation in chronic
      liver diseases.
AB  - Bacterial translocation (BT) has been impeccably implicated as a driving factor
      in the pathogenesis of a spectrum of chronic liver diseases (CLD). Scientific
      evidence accumulated over the last four decades has implied that the disease
      pathologies in CLD and BT are connected as a loop in the gut-liver axis and
      exacerbate each other. Pregnane X receptor (PXR) is a ligand-activated
      transcription factor and nuclear receptor that is expressed ubiquitously along
      the gut-liver-axis. PXR has been intricately associated with the regulation of
      various mechanisms attributed in causing BT. The importance of PXR as the
      mechanistic linker molecule in the gut-liver axis and its role in regulating
      bacterial interactions with the host in CLD has not been explored. PubMed was
      used to perform an extensive literature search using the keywords PXR and
      bacterial translocation, PXR and chronic liver disease including cirrhosis. In an
      adequate expression state, PXR acts as a sensor for bile acid dysregulation and
      bacterial derived metabolites, and in response shapes the immune profile
      beneficial to the host. Activation of PXR could be therapeutic in CLD as it
      counter-regulates endotoxin mediated inflammation and maintains the integrity of
      intestinal epithelium. This review mainly focuses PXR function and its regulation
      in BT in the context of chronic liver diseases.

PMID- 29184612
TI  - Efficacy of Prucalopride in bowel cleansing before colonoscopy: Results of a
      pilot study.
AB  - Colonoscopy is a crucial diagnostic instrument for colorectal cancer screening
      and an adequate bowel preparation is definitely decisive for the success of the
      procedure. Especially in elderly patients, bowel cleansing is considered a big
      issue, because it is often poorly tolerated for many reasons (like inability to
      swallow large volume of liquids or unlikable taste); this can cause a suboptimal
      preparation that may lead to miss a neoplastic lesion. There is relatively little
      data about how to improve preparation tolerability. The purpose of our pilot
      study was to analyze the effect of prucalopride (Resolor(r)), a highly selective
      serotonin 5HT4 receptor agonist used for chronic constipation for its ability to
      stimulate gastrointestinal peristalsis, undertaken the day before colonoscopy,
      followed by half volume of polyethylene glycol solution. We found that this can
      be a good and safe method to achieve an adequate and better-tolerated colon
      cleansing.

PMID- 29184611
TI  - Safety of gastrointestinal endoscopy with conscious sedation in obstructive sleep
      apnea.
AB  - AIM: To perform a systematic review and meta-analysis to assess the safety of
      conscious sedation in patients with obstructive sleep apnea (OSA). METHODS: A
      comprehensive electronic search of MEDLINE and EMBASE was performed from
      inception until March 1, 2015. In an effort to include unpublished data,
      abstracts from prior gastroenterological society meetings as well as other
      reference sources were interrogated. After study selection, two authors utilizing
      a standardized data extraction form collected the data independently. Any
      disagreements between authors were resolved by consensus among four authors. The
      methodological quality was assessed using the Newcastle Ottawa tool for
      observational studies. The primary variables of interest included incidence of
      hypoxia, hypotension, tachycardia, and bradycardia. Continuous data were
      summarized as odds ratio (OR) and 95%CI and pooled using generic inverse variance
      under the random-effects model. Heterogeneity between pooled studies was assessed
      using the I2 statistic. RESULTS: Initial search of MEDLINE and EMBASE identified
      357 citations. A search of meeting abstracts did not yield any relevant
      citations. After systematic review and exclusion consensus meetings, seven
      studies met the a priori determined inclusion criteria. The overall
      methodological quality of included studies ranged from moderate to low. No
      significant differences between OSA patients and controls were identified among
      any of the study variables: Incidence of hypoxia (7 studies, 3005 patients; OR =
      1.11; 95%CI: 0.73-1.11; P = 0.47; I2 = 0%), incidence of hypotension (4 studies,
      2125 patients; OR = 1.10; 95%CI: 0.75-1.60; P = 0.63; I2 = 0%), incidence of
      tachycardia (3 studies, 2030 patients; OR = 0.94; 95%CI: 0.53-1.65; P = 0.28; I2
      = 21%), and incidence of bradycardia (3 studies, 2030 patients; OR = 0.88; 95%CI:
      0.63-1.22; P = 0.59; I2 = 0%). CONCLUSION: OSA is not a significant risk factor
      for cardiopulmonary complications in patients undergoing endoscopic procedures
      with conscious sedation.

PMID- 29184613
TI  - Gender Differences among Patients with Acute Coronary Syndrome in the Middle
      East.
AB  - Background: There is controversy regarding the relationship between gender and
      acute coronary syndrome (ACS). Objective: To study the impact of gender on
      presentation, management, and mortality among patients with ACS in the Middle
      East. Methodology: From January 2012 to January 2013, 4057 patients with ACS were
      enrolled from four Arabian Gulf countries (Kuwait, Oman, United Arab Emirates,
      and Qatar), representing more than 85% of the general hospitals in each of the
      participating countries. Results: Compared to men, women were older and had more
      comorbidities. They also had atypical presentation of ACS such as atypical chest
      pain and heart failure. The prevalence of non-ST-segment elevation myocardial
      infarction (49 vs. 46%; P < 0.001) and unstable angina (34 vs. 24%; P < 0.001)
      was higher among women as compared to men. In addition, women were less likely to
      receive evidence-based medications such as aspirin, clopidogrel, beta-blocker,
      and angiotensin-converting enzyme inhibitors on admission and on discharge.
      During hospital stay, women suffered more heart failure (15 vs. 12%; P = 0.008)
      and were more likely to receive blood transfusion (6 vs. 3%; P < 0.001). Women
      had higher 1-year mortality (14 vs. 11%; P < 0.001), the apparent difference that
      disappeared after adjusting for age and other comorbidities. Conclusion: Although
      there were differences between men and women in presentation, management, and in
      hospital outcomes, gender was shown to be a nonsignificant contributor to
      mortality after adjusting for confounders.

PMID- 29184614
TI  - Idiopathic Fascicular Left Ventricular Tachycardia.
AB  - Idiopathic left fascicular ventricular tachycardia (ILFVT) is characterized by
      right bundle branch block morphology and left axis deviation. We report a case of
      idiopathic left ventricular fascicular tachycardia in a young 31-year-old male
      patient presenting with a narrow complex tachycardia.

PMID- 29184616
TI  - Hybrid Completion of Aortic Repair after Type A Aortic Dissection in a Patient
      with Marfan's Syndrome.
AB  - Medicine and engineering are in collaboration to assist in the tackling of
      daunting surgical techniques which are associated with high rates of morbidity
      and mortality, in exchange for minimally invasive approaches with lower
      procedural risk. Endovascular procedures in general have already reduced the risk
      of surgery by limiting the extent of open surgery and often replacing it with
      purely percutaneous or hybrid procedures. Here, we describe a patient who had
      complex staged surgery with open repair of a proximal portion of a type A aortic
      dissection followed by a staged endovascular reconstruction of the arch and
      descending aorta by means of a fenestrated stent-graft to secure the left
      subclavian artery and the posterior cerebral circulation.

PMID- 29184615
TI  - Mobitz Type II Atrioventricular Block following Tramadol and Fentanyl in a
      Patient with Acute Coronary Syndrome and Systolic Heart Failure.
AB  - Serotonin syndrome is a potentially fatal condition allied with increased
      serotonergic activity in the central nervous system. There are published data
      reporting serotonin syndrome induced by either tramadol or fentanyl in
      combination with selective serotonin reuptake inhibitors in adult patients;
      however, there are no reports of serotonin syndrome resulting from the
      combination of tramadol and fentanyl. We report a case of a 52-year-old woman who
      was admitted to cardiology service and who developed Mobitz Type II
      atrioventricular (AV) block after administration of oral tramadol and intravenous
      fentanyl.

PMID- 29184617
TI  - Acute Atrial Fibrillation Complicating Organophosphorus Poisoning.
AB  - Organophosphorus (OP) pesticide poisoning is a major clinical and public health
      problem in a developing country like India. Cardiac injury is a strong predictor
      of death in these patients. Cardiac complications usually described include
      cardiac arrest, pulmonary edema, and arrhythmia. Rarely, myocardial infarction
      has also been reported. The possible mechanisms for myocardial injury include
      sympathetic/parasympathetic overactivity, hypoxemia, acidosis, dyselectrolytemia,
      and direct cardiotoxicity. We describe herein one case of OP poisoning, recently
      admitted in our emergency department and which was complicated by acute onset
      atrial fibrillation which reverted to sinus rhythm following detoxification of OP
      compound.

PMID- 29184618
TI  - Off-pump Coronary Artery Bypass Surgery in a Patient with Dextrocardia and Situs
      Inversus: Anesthetic, Surgical Consideration and Role of Transesophageal
      Echocardiography.
AB  - Coronary artery bypass surgery (CABG) in dextrocardia with situs inversus
      patients is reported less in literature. Due to abnormal looping and associated
      other congenital anomalies, anesthetic implications and surgical difficulties
      become challenging in these patients. Transesophageal echocardiography
      examination (TEE) needs multiplane angle adjustments compared to normal heart to
      obtain the images. Here, we describe a 53-year-old female patient having
      dextrocardia with situs inversus who underwent CABG and discuss the perioperative
      management and multiplane adjustments during TEE examination.

PMID- 29184619
TI  - Guidelines To Writing A Clinical Case Report.

PMID- 29184620
TI  - Large Pericardial Mass Mimicking Pericardial Effusion.

PMID- 29184621
TI  - Painting with Bacteria.

PMID- 29184622
TI  - Risk Factors for Coronary Artery Disease: Historical Perspectives.

PMID- 29184623
TI  - Neutral sphingomyelinases control extracellular vesicles budding from the plasma
      membrane.
AB  - Extracellular vesicles (EVs) are membrane particles secreted from cells into all
      body fluids. Several EV populations exist differing in size and cellular origin.
      Using differential centrifugation EVs pelleting at 14,000 g ("microvesicles"
      (MV)) and 100,000 g ("exosomes") are distinguishable by protein markers. Neutral
      sphingomyelinase (nSMase) inhibition has been shown to inhibit exosome release
      from cells and has since been used to study their functional implications. How
      nSMases (also known as SMPD2 and SMPD3) affect the basal secretion of MVs is
      unclear. Here we investigated how SMPD2/3 impact both EV populations. SMPD2/3
      inhibition by GW4869 or RNAi decreases secretion of exosomes, but also increases
      secretion of MVs from the plasma membrane. Both populations differ significantly
      in metabolite composition and Wnt proteins are specifically loaded onto MVs under
      these conditions. Taken together, our data reveal a novel regulatory function of
      SMPD2/3 in vesicle budding from the plasma membrane and clearly suggest that -
      despite the different vesicle biogenesis - the routes of vesicular export are
      adaptable.

PMID- 29184624
TI  - Is your article EV-TRACKed?
AB  - The EV-TRACK knowledgebase is developed to cope with the need for transparency
      and rigour to increase reproducibility and facilitate standardization of
      extracellular vesicle (EV) research. The knowledgebase includes a checklist for
      authors and editors intended to improve the transparency of methodological
      aspects of EV experiments, allows queries and meta-analysis of EV experiments and
      keeps track of the current state of the art. Widespread implementation by the EV
      research community is key to its success.

PMID- 29184625
TI  - Confounding factors in vesicle uptake studies using fluorescent lipophilic
      membrane dyes.
AB  - Small extracellular vesicles (sEVs) such as exosomes are nanocarriers of
      proteins, RNAs and DNAs. Isolation of pure sEV populations remains challenging,
      with reports of protein and lipoprotein contaminants in the isolates. Cellular
      uptake - a cornerstone for understanding exosome and sEV function - is frequently
      examined using lipophilic dyes such as PKH67 or CellMask to label the vesicles.
      In this study, we investigated whether contaminants can confound the outcomes
      from sEV and exosomes uptake experiments. sEVs were isolated from blood plasma of
      fasted or non-fasted rats as well as from serum-supplemented or serum-free
      conditioned cell culture medium using size-exclusion chromatography (SEC). Eluent
      fractions were characterized using nanoparticle tracking, protein and
      triglyceride assays and immunoassays. SEC fractions were labelled with different
      lipophilic dyes and cellular uptake was quantified using endothelial cells or
      primary cardiomyocytes. We report co-isolation of sEVs with apolipoprotein B
      containing lipoproteins. Cellular dye transfer did not correspond to sEV content
      of the SEC fractions, but was severely affected by lipoprotein and protein
      content. Overnight fasting of rats decreased lipoprotein content and also
      decreased dye transfer, while late, sEV-poor/protein-rich fractions demonstrated
      even greater dye transfer. The potential for dye transfer to occur in the
      complete absence of sEVs was clearly shown by experiments using staining of sEV
      depleted serum or pure protein sample. In conclusion, proteins and lipoproteins
      can make a substantial contribution to transfer of lipophilic dyes to recipient
      cells. Considering the likelihood of contamination of sEV and exosome isolates,
      lipophilic dye staining experiments should be carefully controlled, and
      conclusions interpreted with caution.

PMID- 29184626
TI  - Updating the MISEV minimal requirements for extracellular vesicle studies:
      building bridges to reproducibility.

PMID- 29184627
TI  - Medical sequencing of de novo ectodermal dysplasia in identical twins and
      evaluation of the potential eligibility for recombinant EDA therapy.
AB  - The purpose of this study was to test two 8-year-old identical twins with
      ectodermal dysplasia (ED) and their unaffected parents for the presence of
      mutations in the EDA gene with the hypothesis that they might be carrying a de
      novo mutation in EDA and potentially eligible for recombinant EDA therapy. DNA
      was extracted using saliva samples obtained from the identical twin girls and
      both parents. PCR products of Ectodyplasin A (EDA), Ectodysplasin Receptor
      (EDAR), Ectodysplasin Receptor Associated Death Domain (EDARADD), and Connexin-30
      (GJB6) were sequenced by the Sanger method and the results analyzed using a
      reference sequence. Exons and exon-intron boundaries of EDA, EDAR, EDARADD, and
      GJB6 were sequenced in both parents and the affected identical twin pair. No
      mutations were detected in EDA or GJB6. Genetic variants located in the intron of
      EDAR were found but determined to be non-contributory to the twins' ED. A
      microsatellite polymorphism was detected in all four subjects in exon 4 of the
      EDARADD gene but determined not to be causal to the ED. There was a silent
      mutation detected in exon 6 of the EDARADD gene of both the daughters and their
      unaffected mother but also unlikely to be the cause of ED. These results suggest
      that ED of the subjects is caused by a de novo mutation in a gene not studied
      here. It is likely these subjects and their future offspring would not benefit
      from the development of recombinant EDA replacement therapy.

PMID- 29184628
TI  - Comparison of in vitro properties of periodontal ligament stem cells derived from
      permanent and deciduous teeth.
AB  - Background. Stem cells have contributed to the development of tissue-engineered
      based regenerative periodontal therapies. In order to find the best stem cell
      sources for such therapies, the biologic properties of stem cells isolated from
      periodontal ligaments (PDL) of deciduous (DePDLSC) and permanent (PePDLSC) teeth
      were comparatively evaluated. Methods. PDL stem cells were isolated from six
      sound fully erupted premolars and six deciduous canines of healthy subjects. In
      vitro biologic characteristics such as colony formation, viability, stem cell
      marker identification and osteogenic differentiation (using alkaline phosphatase
      analysis and Alizarin red staining) were comparatively assessed using one-way
      ANOVA and post hoc Tukey tests using SPSS 13.0. Results. Stem cell populations
      isolated from both groups were CD105+ and CD90+ and CD45-. No statistically
      significant differences were found in stem cell markers, colony formation and
      viability. Both groups were capable of osteogenic differentiation. However,
      alkaline phosphatase activity test showed a statistically significant difference,
      with PePDLSC exhibiting higher alkaline phosphatase activity (P=0.000). No
      statistically significant difference was seen in quantitative alizarine red
      staining (P=0.559). Conclusion. Mesenchymal stem cells of PDL could successfully
      be isolated from permanent and deciduous teeth. A minor difference was observed
      in the osteogenic properties of the two cell types, which might affect their
      future clinical applications.

PMID- 29184629
TI  - Stress distribution pattern of screw-retained restorations with segmented vs. non
      segmented abutments: A finite element analysis.
AB  - Background. Screw-retained restorations are favored in some clinical situations
      such as limited inter-occlusal spaces. This study was designed to compare
      stresses developed in the peri-implant bone in two different types of screw
      retained restorations (segmented vs. non-segmented abutment) using a finite
      element model. Methods. An implant, 4.1 mm in diameter and 10 mm in length, was
      placed in the first molar site of a mandibular model with 1 mm of cortical bone
      on the buccal and lingual sides. Segmented and non-segmented screw abutments with
      their crowns were placed on the simulated implant in each model. After loading
      (100 N, axial and 45 degrees  non-axial), von Mises stress was recorded using
      ANSYS software, version 12.0.1. Results. The maximum stresses in the non
      segmented abutment screw were less than those of segmented abutment (87 vs. 100,
      and 375 vs. 430 MPa under axial and non-axial loading, respectively). The maximum
      stresses in the peri-implant bone for the model with segmented abutment were less
      than those of non-segmented ones (21 vs. 24 MPa, and 31 vs. 126 MPa under
      vertical and angular loading, respectively). In addition, the micro-strain of
      peri-implant bone for the segmented abutment restoration was less than that of
      non-segmented abutment. Conclusion. Under axial and non-axial loadings, non
      segmented abutment showed less stress concentration in the screw, while there was
      less stress and strain in the peri-implant bone in the segmented abutment.

PMID- 29184630
TI  - Effect of flap design and duration of surgery on acute postoperative symptoms and
      signs after extraction of lower third molars: A randomized prospective study.
AB  - Background. Different surgical variables are assumed to play a role in
      postoperative course after lower third molar extraction. The aim of study was to
      assess whether flap design and duration of surgery can influence acute
      postoperative symptoms and signs after lower third molar extraction. Methods.
      Twenty-five patients scheduled for lower third molar extraction were included in
      this study and randomly assigned to two groups in terms of flap design: group A
      (envelope flap) and group B (triangular flap). Swelling and trismus were assessed
      before and after surgery on days 0, 2 and 7. Pain was assessed for seven days
      after surgery. Maximum postoperative pain was chosen as the main outcome
      variable. ANOVA was used to assess differences between the groups regarding
      maximum postoperative pain, trismus and swelling at 2- and 7-day intervals.
      Pearson's correlation coefficient was used to assess correlation between duration
      of surgery and postoperative symptoms and signs. Results. No significant
      difference was found between the two flap designs for any postoperative symptoms
      and signs. The duration of surgery was found to be correlated with both trismus
      (r = -0.44, P = 0.04) and swelling (r = 0.59, P = 0.004) as assessed 2 days after
      surgery. No associations were found between duration of surgery and maximum
      postoperative pain and trismus and swelling at 7-day interval. Conclusion. Within
      the limits of the present study, the duration of surgery, and not the flap
      design, affected the acute postoperative symptoms and signs after lower third
      molar extraction.

PMID- 29184631
TI  - Comparison of the accuracy of conventional and digital radiography in root canal
      working length determination: An invitro study.
AB  - Background. Digital radiography has widespread use in endodontics. Determining a
      correct working length is vital for a proper endodontic therapy. The aim of this
      study was to compare the accuracy of conventional and digital radiographic
      techniques for root canal working length determination. Methods. After
      determining the real working lengths of 50 permanent maxillary central incisors
      (gold standard), the conventional (E- and F-speed films) and digital (CCD, PSP)
      images were obtained using the parallel technique. The mean registered working
      length of each modality was compared with the other and with the gold standard
      using one-way ANOVA at P<0.05. Results. No significant difference was found
      between the recorded working length values using the conventional and digital
      radiographic techniques (P=0.828). Conclusion. Within the limitations of this
      study, it was concluded that there was no difference between the measurement
      accuracy of CCD, PSP and conventional imaging techniques in root canal working
      length determination.

PMID- 29184632
TI  - Deep neck infection after third molar extraction: A case report.
AB  - Deep neck infections are associated with high morbidity rates in dentistry. Early
      diagnosis and intervention play an essential part in decreasing morbidity rates.
      The present study aims to report a case of odontogenic deep neck infection after
      third molar extraction. A 51-year-old male patient underwent extraction of the
      mandibular right third molar. Seven days later, the patient developed symptoms
      and signs of progressive infection. Laboratorial and radiologic examinations in
      association with clinical investigations confirmed deep neck infection. Extraoral
      drainage was performed under orotracheal intubation. Postoperative laboratory
      tests and clinical examinations revealed signs of complete remission within a
      follow-up period of 10 days. Considering the invasive nature of pathogens related
      to deep neck infections, it is possible to infer that a combination of accurate
      diagnosis and early intervention plays an essential role in the field of
      maxillofacial surgery and pathology.

PMID- 29184633
TI  - Association between demographic and radiographic characteristics of the
      schneiderian membrane and periapical and periodontal diseases using cone-beam
      computed tomography scanning: A retrospective study.
AB  - Background. This study was undertaken to assess the pathological and spatial
      associations between periapical and periodontal diseases of the maxillary first
      molars and thickening of maxillary sinus mucosa with cone-beam computed
      tomography. Methods. A total of 132 CBCT images of subjects 20-60 years of age
      were evaluated retrospectively. The patients' sex and age and demographic and
      pathologic findings of the maxillary sinus in the first molar area were recorded,
      graded and analyzed. Results. Approximately 59% of patients were male and 41%
      were female, with no significant difference in the thickness of schneiderian
      membrane between males and females. Based on the periapical index scoring, the
      highest frequency was detected in group 1. Based on the results of ANOVA, there
      were no significant differences in the frequencies of endodontic-periodontal
      lesions and an increase in schneiderian membrane thickness. There were
      significant relationships between periapical and periodontal infections (P<0.001)
      and schneiderian membrane thickness. Furthermore, a significant relationship was
      detected between the thickness of the schneiderian membrane and the distance
      between the sinus floor and the root apices (P=0.38). Conclusion. A retrospective
      inspection of CBCT imaging revealed that periapical lesions and periodontal
      infections in the posterior area of the maxilla were associated with thickening
      of the schneiderian membrane. In addition, there was a significant relationship
      between the location of maxillary posterior teeth, i.e. the thickness of bone
      from the root apex to the maxillary sinus floor, and schneiderian membrane
      thickness.

PMID- 29184634
TI  - Effect of a passive sonic irrigation system on elimination of Enterococcus
      faecalis from root canal systems of primary teeth, using different concentrations
      of sodium hypochlorite: An in vitro evaluation.
AB  - Background. This in vitro study aimed to compare the antibacterial effect of
      different concentrations of sodium hypochlorite on elimination of Enterococcus
      faecalis from root canal systems of primary teeth with or without a passive sonic
      irrigation system (EndoActivator). Methods. The root canals of 120 extracted
      single-rooted primary incisors were prepared using the crown-down technique. The
      teeth were autoclaved and inoculated with E. faecalis. The infected samples were
      then randomly divided into 6 experimental groups of 15 and positive and negative
      control groups as follows: group 1: 0.5% sodium hypochlorite solution; group 2:
      2.5% sodium hypochlorite solution; group 3: 5% sodium hypochlorite solution;
      group 4: 0.5% sodium hypochlorite solution + sonic activation; group 5: 2.5%
      sodium hypochlorite solution + sonic activation; and group 6: 5% sodium
      hypochlorite solution + sonic activation. Microbiological samples were collected
      before and after disinfection procedures and the colony-forming units were
      counted. Statistical analyses were performed using the two-way ANOVA and post hoc
      Duncan's tests in cases of significant difference. Results. There were no
      significant differences between the groups in any of the variables (concentration
      of antiseptic or use of sonic irrigation system). Conclusion. Use of passive
      sonic irrigation systems in endodontic treatment of single-rooted primary teeth
      is of no benefit compared to regular needle irrigation. The results of this study
      also recommends use of lower concentrations of sodium hypochlorite solution
      (0.5%) for irrigation of the root canal system rather than higher concentrations
      given approximately equal efficacy.

PMID- 29184635
TI  - Effect of denture cleansing agents on tensile and shear bond strengths of soft
      liners to acrylic denture base.
AB  - Background. The aim of the present study was to evaluate the effect of Corega and
      2.5% sodium hypochlorite cleansing agents on the shear and tensile bond strengths
      of GC soft liner to denture base. Methods. A total of 144 samples (72 samples for
      tensile and 72 for shear bond strength evaluations) were prepared. The samples in
      each group were subdivided into three subgroups in terms of the cleansing agent
      used (2.5% sodium hypochlorite, Corega and distilled water [control group]). All
      the samples were stored in distilled water, during which each sample was immersed
      for 15 minutes daily in sodium hypochlorite or Corega solutions. After 20 days
      the tensile and shear bond strengths were determined using a universal testing
      machine. In addition, a stereomicroscope was used to evaluate fracture modes.
      Data were analyzed with one-way ANOVA, using SPSS 16. Results. The results of
      post hoc Tukey tests showed significant differences in the mean tensile and shear
      bond strength values between the sodium hypochlorite group with Corega and
      control groups (P=0.001 for comparison of tensile bond strengths between the
      sodium hypochlorite and control groups, and P<0.001 for the comparison of tensile
      bond strengths between the sodium hypochlorite and Corega groups and the shear
      bond strengths between the sodium hypochlorite and Corega groups, and sodium
      hypochlorite and control groups).The majority of failures were cohesive in the
      control and Corega groups and cohesive/adhesive in the sodium hypochlorite group.
      Conclusion. Immersion of soft liners in Corega will result in longevity of soft
      liners compared to immersion in sodium hypochlorite solution and sodium
      hypochlorite solution significantly decreased the tensile and shear bond
      strengths compared to the control and Corega groups.

PMID- 29184636
TI  - Efficacy of radiographic density values of the first and second cervical
      vertebrae recorded by CBCT technique to identify patients with osteoporosis and
      osteopenia.
AB  - Background. Osteoporosis is a systemic skeletal disease characterized by a
      decrease in bone strength with an increase in the risk of fractures. This study
      aimed at evaluating the ability to predict osteoporosis and osteopenia based on
      radiographic density values obtained from CBCT imaging technique. Methods. CBCT
      images of 108 patients were prepared by using NewTom VGI (QR, Verona, Italy).
      Then the patients were assigned to osteoporosis, osteopenia and healthy group,
      using the T-score derived from the DEXA technique. Finally, RD of the lateral
      mass of C1 on the left and right sides and body and dens of the C2 were measured.
      RD values were compared between the three groups by one-way ANOVA, followed by an
      appropriate post hoc test. Results. The results of the comparisons of RD values
      at the first and second cervical vertebrae in the three groups showed that all
      the values had statistically significant differences (P<0.05). The most precise
      diagnosis of osteoporosis was related to the RD values of the body of C2 and left
      lateral mass of C1 that was equal to 99% and their cut-off points were 375 and
      386, respectively. Conclusion. Based on the findings of this study, it is
      possible to predict the osteoporosis status of the patient through the RD related
      to the body of C2 and the left lateral mass of C1 more accurately than the other
      areas.

PMID- 29184637
TI  - Preliminary study of a novel dental hand instrument for restorative procedures.
AB  - Background. There is no clear consensus on operative hand instrumentation. In
      general, there is one hand instrument that completes one task. Consequently,
      numerous instruments are required for the placement, shaping and carving of a
      restoration. This reduces clinical efficiency, increases cost and may generate
      frustration. Methods. A novel dental hand instrument has been developed. The
      instrument (GTI) can complete several tasks. The instrument was assessed in a
      laboratory setting with amalgam, composite and glass-ionomer restorations on
      dentoform teeth. Results. Results indicated that class II amalgam and composite
      restorations were significantly faster than conventional instrumentation
      (P<0.05). Differences in restoration quality were not statistically significant.
      Cost was significantly reduced as the GTI could perform the task of 9
      conventional instruments. Conclusion. The GTI is an industry-translated, novel
      medical device that offers the clinician an alternative to standard
      instrumentation. Further investigations are required with increased samples
      sizes, clinical assessment and expanded utility.

PMID- 29184638
TI  - Promoting the Quality of Health Research-based News: Introduction of a Tool.
AB  - Introduction: While disseminating health research findings to the public, it is
      very important to present appropriate and accurate information to give the target
      audience a correct understanding of the subject matter. The objective of this
      study was to design and psychometrically evaluate a checklist for health
      journalists to help them prepare news of appropriate accuracy and authenticity.
      Methods: The study consisted of two phases, checklist design and psychometrics.
      Literature review and expert opinion were used to extract the items of the
      checklist in the first phase. In the second phase, to assess content and face
      validity, the judgment of 38 persons (epidemiologists with a tool production
      history, editors-in-chief, and health journalists) was used to check the items'
      understandability, nonambiguity, relevancy, and clarity. Reliability was assessed
      by the test-retest method using intra-cluster correlation (ICC) indices in the
      two phases. Cronbach's alpha was used to assess internal validity of the
      checklist. Results: Based on the participants' opinions, the items were reduced
      from 20 to 14 in number. The items were categorized into the following three
      domains: (a) items assessing the source of news and its validity, (b) items
      addressing the presentation of complete and accurate information on research
      findings, and (c) items which if adhered to lead to the target audiences' better
      understanding. The checklist was approved for content and face validity. The
      reliability of the checklist was assessed in the last stage; the ICC was 1 for 12
      items and above 0.8 for the other two. Internal consistency (Cronbach's alpha)
      was 0.98. Discussion and Conclusions: The resultant indices of the study indicate
      that the checklist has appropriate validity and reliability. Hence, it can be
      used by health journalists to develop health research-based news.

PMID- 29184639
TI  - Social Determinants of Health and Attempt to Change Unhealthy Lifestyle: A
      Population-based Study.
AB  - Background: A healthy lifestyle is important because of its long-term benefits;
      however, there is a paucity of information concerning health choices among
      Iranians. We evaluated personal health behaviors, attempts to change unhealthy
      behaviors, and factors affecting attempts at change. Methods: The design of this
      cross-sectional study was to assemble a representative cadre of >18-year-old
      adults in Shiraz, Iran, using a multistage cluster sampling technique. Validated
      questionnaires collected participant's demographic information, such as weight,
      height, cigarette smoking history, physical activity, and attempts at lifestyle
      changes during the previous year. To determine predictors of attempts to change
      unhealthy lifestyle and to identify confounders, we applied single and
      multivariable logistic regression methods, respectively. A confidence interval of
      95% was calculated for each odds ratio. Results: The prevalence of attempts to
      change unhealthy lifestyle was 42%, 64.8%, and 27.8%, respectively, for losing
      weight, being more physically active, and smoking cessation. Unemployment, low
      levels of education, and decreased socioeconomic status have important roles in
      attempts to change lifestyle conditions. Low socioeconomic status was a risk
      factor for quitting smoking. Occupation (unemployed/homemaker) and low level of
      education were two significant factors for being more physically active.
      Conclusions: The prevalence of inadequate physical activity and being overweight
      or obese was considerable in Shiraz, Iran. Attempts to change unhealthy lifestyle
      were less than ideal. Social determinants of health factors including
      unemployment and low levels of education and socioeconomic status play important
      roles in attempts to change current lifestyles.

PMID- 29184640
TI  - Investigation of Five Common Mutations on Phenylalanine Hydroxylase Gene of
      Phenylketonuria Patients from Two Provinces in North of Iran.
AB  - Background: There are more than 500 different mutations on phenylalanine
      hydroxylase (PAH) gene that is responsible for phenylketonuria (PKU) diseases and
      the spectrum of these mutations is varied in different populations. The main
      clinical manifestation of untreated patients is severe mental retardation. The
      PAH gene, that is 90 kb long, is consisted of 13 exons and 12 introns. The aim of
      the present study was to identify the frequency of five common mutations on PAH
      gene among patients with PKU in Mazandaran and Golestan provinces including
      c.1066-11G>A, p. R261Q, p. R252W, p. R261X, and c.1200 + 1G>C. Methods: Forty
      unrelated PKU patients, that 22 of them, were from Mazandaran and 18 of them from
      Golestan provinces were enrolled in the study. Genomic DNA was extracted from
      leukocytes using Qiagen DNA extraction kit and polymerase chain reaction -
      restriction fragment length polymorphism method was applied to detect five common
      mutations. Results: Three out of the 5 investigate mutations were identified
      among the patients. The c.1066-11G>A mutation has the highest frequency (27.5%)
      among the patients and the frequency of p. R261Q and p. R261X mutations were 3.75
      and 1.25%, respectively. In Golestan province, only c.1066-11G>A mutation was
      observed in investigated alleles. Conclusions: The high frequency of c.1066-11G>A
      mutation in Golestan province may be related to genetic drift, founder effect,
      and consanguinity.

PMID- 29184642
TI  - Bhutan and Maldives Eliminate Measles: World Health Organization.

PMID- 29184641
TI  - Modeling The Underlying Tobacco Smoking Predictors Among 1st Year University
      Students In Iran.
AB  - Background: There are scant studies on the prevalence and determinants of tobacco
      smoking among 1st year university students in Iran. We aim to determine the
      prevalence of substance abuse and identify factors related with tobacco smoking
      in 1st year students of Qazvin University of Medical Sciences (QUMS). Methods: A
      self-administered questionnaire was used to collect information on
      sociodemographic, cigarette smoking, hookah smoking, and related risk factors
      among 521 1st year students in QUMS between January and February 2014. We used
      logistic regression to determine factors associated with substance abuse among
      students. Results: The descriptive statistics indicated that the prevalence of
      lifetime cigarette and hookah smoking was 8.6% (confidence interval [CI] 95%: 6.5
      11.4) and 35.5% (CI 95%: 31.5-39.7), respectively. After adjustment for other
      factors, being male, the presence of any smoker in the family and having smoker
      friends were factors associated with cigarette and hookah smoking among students.
      Our findings also revealed the co-occurrence of risk-taking behaviors among
      students. Conclusions: Our study showed considerably low prevalence of tobacco
      smoking among 1st year students. Longitudinal studies are necessary to approve
      the observed results of this study and thus allow for a certain generalization of
      the observations.

PMID- 29184643
TI  - Development of Caries Risk Assessment Tool for Iranian Preschoolers: A Primary
      Validation Study.
AB  - Background: The aim of the present study was to develop a dental caries risk
      assessment tool for Iranian preschoolers. Methods: In a validation and cross
      sectional study, a random sample of 150 preschool children was involved. This
      study was conducted in three phases: questionnaire design (expert panel and peer
      evaluation), questionnaire testing (pilot evaluation and field testing), and
      validation study. The initial assessments include interview, dental examination,
      and laboratory investigations. Validity and reliability indices, content validity
      index (CVI), content validity ratio (CVR), impact score, and test-retest and
      Cronbach's alpha were measured. Decayed, missing, filled teeth (dmft) scores were
      calculated according to the WHO guidelines. Results: The Iranian version of
      caries risk assessment (CRA) questionnaire contained 17 items. Cronbach's alpha
      coefficient (0.86) indicated a suitable internal consistency. The mean scores for
      the CVI and the CVR were 0.87 and 0.78, respectively. The prevalence rate of
      dental caries in the study group was 69.3%, and the mean dmft was 4.57 (range 0
      19). Conclusions: The Persian version of CRA questionnaire was adapted to the
      Iranian population. The findings demonstrated overall acceptable validity and
      also reliability in the application of test-retest. The results of the present
      study provide initial evidence that the designed CRA form could be a useful tool
      for CRA in the Iranian preschoolers.

PMID- 29184645
TI  - Ensuring Tobacco Control to Strengthen the Economy of a Nation and Improve the
      Health Standards of the Population.

PMID- 29184644
TI  - Incidence of Neonatal Hyperphenylalaninemia Based on High-performance Liquid
      Chromatography Confirmatory Technique in Mazandaran Province, Northern Iran (2007
      2015).
AB  - Background: Classic phenylketonuria (PKU) is a metabolic disorder. The purpose of
      this study was to assess epidemiological factors of PKU phenotypes in a neonatal
      screening program for Mazandaran, Iran. Methods: In this descriptive
      retrospective study from 2007 to 2015, neonates PKU level was conducted by
      phenylalanine level based on a biochemical technique by ELISA and then by
      confirmatory methods high performance liquid chromatography. Results: Of the
      407,244 screened newborns (48.7% girls and 51.3% boys), 14 girls and 13 boys were
      diagnosed definitely from 465 suspicious cases of PKU. The incidence of PKU was
      0.66 in 10,000, which was noted in different severity (severe PKU - 1:67,874,
      mild PKU - 1:45,249, and HPA - 1:33,937). In addition, we did not detect any
      cases of nonclassic PKU. Conclusions: Although the consanguineous marriage
      pattern is a major cause of hyperphenylalaninemia (HPA) particularly in Iranian,
      there was no significant difference between groups in this study. Now, screening
      should be executed for all of the family that they have the familial history of
      PKU in Iran. According to varies actual of prevalence and incidence rate of PKU
      reported a real patient and taking PKU with mild PKU and HPA, it is recommended,
      the will provide the PKU reports based on the severity of the disease.

PMID- 29184646
TI  - Are Gender Differences in Health-related Quality of Life Attributable to
      Sociodemographic Characteristics and Chronic Disease Conditions in Elderly
      People?
AB  - Background: The objective of this study was to determine the gender differences
      in health-related quality of life (HRQoL) and to indicate to what extent this
      difference can be explained by differential in demographic and chronic disease
      conditions in Iranian elderly people. Methods: This analysis was carried out on
      cross-sectional data of QoL assessment among 750 elderly individuals aged 60-90
      years who were dwelling in urban population of Babol, the North of Iran. The
      multiple linear regression model was used to estimate the association between
      gender and HRQoL after controlling sociodemographic characteristics and chronic
      disease conditions. Results: Women had significantly lower score in HRQoL in all
      subscales compared with men after adjusting several confounding factors (P =
      0.001). The unadjusted mean difference in overall HRQoL scores was -11.2 (95%
      confidence interval [CI]: -13.8, -8.6) points, but it was reduced to -6.5 (95%
      CI: -9.0, -3.9) points between gender after adjusting by age, educational level,
      living status, physical activity, smoking, abdominal obesity, diabetes, and
      hypertension. Conclusions: Adjusting for sociodemographic and chronic disease
      conditions reduced the effect size of poorer HRQoL for women compared with men
      but did not remove the sex differences. The poorer scores of HRQoL in Iranian
      women needs further physical, psychological, and social supports in elderly.

PMID- 29184647
TI  - Medicinal Plants, Effective Plant Compounds (Compositions) and their Effects on
      Stomach Cancer.
AB  - Medicinal plants have special importance around the world. Further, they have
      been noticed for nutrition and illness treatment such as preparation of
      anticancer new drugs. Therefore, a wide range of studies have been done on
      different plants, and their anticancer effects have been investigated. Nowadays,
      cancer is the most important factor of death rate in the developed and developing
      countries. Among them, stomach cancer is one of the most common malignancies
      around the world. At present, it is recognized as the fourth common cancer and
      the second factor of death rate due to cancer. So far, there has been wide range
      of effort for cancer treatment; however, in most cases, the response to the
      treatment has been very weak and often accompanied improper subsidiary effects.
      The present problems as a consequence of chemical treatment and radiotherapy and
      many subsidiary problems created due to their use for patients, and also, the
      resistance to the current treatment has motivated researchers to apply new
      medicines with more effect and less toxicity. The secondary metabolisms existent
      in the plants have an important role in the treatment of several diseases such as
      cancer. This study was conducted to investigate and collect scientific results
      for stomach cancer and to clarify the role of medicinal plants and secondary
      plant compounds on its treatment.

PMID- 29184648
TI  - Estimating the prevalence of Positive Tuberculin Skin Test Reactions in General
      Population and High-risk Groups: A Meta-analysis.
AB  - Results of tuberculin skin test (TST) surveys among different populations have
      been reported in many studies as a method for detecting primary Mycobacterium
      tuberculosis infection. Combining these results provides reliable estimates of
      primary latent tuberculosis (TB) infection for health policymakers. This study
      aims to estimate the prevalence of latent TB infection in general and high-risk
      populations in Iran. National and international databanks were searched using
      specific keywords. After restricting the search strategy, duplicates exclusion,
      reviewing titles, abstracts and full texts, and quality assessment, eligible
      papers were selected. The heterogeneity between the results was assessed
      according to Cochrane and I-squared indices. The prevalence of positive TST
      reactions was estimated using fixed and random effect models. Totally, 33 papers
      were entered into the meta-analysis reporting the TST results in 12693 people
      aged over 18. The prevalence (95% confidence intervals) of positive TST reactions
      in all groups, general population, health staff, medical students, household
      close contacts, patients with TB, immunocompromised patients, HIV/AIDS patients,
      and those with risky behaviors was 26.2% (19.6-32.8), 25.4% (4.8-46.1), 38.9%
      (27.4-50.9), 13.4% (9.9-16.7), 35.9% (16.4-55.5), 13.7% (8.4-18.9), 29.4% (21.2
      37.7), and 14.6% (3.9-25.3), respectively. Our study showed great varieties of
      positive TST results among different Iranian subpopulations. Furthermore, the
      prevalence of latent TB infection among health professionals and family members
      of TB patients was considerably different from that of the other subgroup. Since
      TB control programs such as active case finding are routinely conducted among
      household close contacts and HIV/AIDS cases, other high-risk groups including
      health-care workers and immunocompromised patients should be taken into
      consideration in these preventive programs.

PMID- 29184649
TI  - Tympanometric profiles for Chinese older adults.

PMID- 28663787
TI  - CyTOF workflow: differential discovery in high-throughput high-dimensional
      cytometry datasets.
AB  - High dimensional mass and flow cytometry (HDCyto) experiments have become a
      method of choice for high throughput interrogation and characterization of cell
      populations.Here, we present an R-based pipeline for differential analyses of
      HDCyto data, largely based on Bioconductor packages. We computationally define
      cell populations using FlowSOM clustering, and facilitate an optional but
      reproducible strategy for manual merging of algorithm-generated clusters. Our
      workflow offers different analysis paths, including association of cell type
      abundance with a phenotype or changes in signaling markers within specific
      subpopulations, or differential analyses of aggregated signals. Importantly, the
      differential analyses we show are based on regression frameworks where the HDCyto
      data is the response; thus, we are able to model arbitrary experimental designs,
      such as those with batch effects, paired designs and so on. In particular, we
      apply generalized linear mixed models to analyses of cell population abundance or
      cell-population-specific analyses of signaling markers, allowing overdispersion
      in cell count or aggregated signals across samples to be appropriately modeled.
      To support the formal statistical analyses, we encourage exploratory data
      analysis at every step, including quality control (e.g. multi-dimensional scaling
      plots), reporting of clustering results (dimensionality reduction, heatmaps with
      dendrograms) and differential analyses (e.g. plots of aggregated signals).

PMID- 29123644
TI  - RNAi targeting Caenorhabditis elegans alpha-arrestins has little effect on
      lifespan.
AB  - Background: alpha-arrestins are a family of proteins that are implicated in
      multiple biological processes, including metabolism and receptor desensitization.
      Methods: Here, we sought to examine the roles of alpha-arrestins in the longevity
      of Caenorhabditis elegans through an RNA interference screen. Results: We found
      that knocking down each of 24 out of total 29 C. elegans alpha-arrestins had
      little effect on lifespan. Thus, individual C. elegans alpha-arrestins may have
      minor effects on longevity. Conclusions: This study will provide useful
      information for future research on the functional role of alpha-arrestins in
      aging and longevity.

PMID- 29184653
TI  - Guest Editors' Foreword: Special Issue on Augmented Environments for Computer
      Assisted Interventions CAI systems enable more precise, safer, and less invasive
      interventional treatments.

PMID- 29152223
TI  - Stage 1 Registered Report: Effect of deficient phagocytosis on neuronal survival
      and neurological outcome after temporary middle cerebral artery occlusion
      (tMCAo).
AB  - Stroke is a major cause of death and disability worldwide. In addition to
      neuronal death resulting directly from energy depletion due to lack of blood
      supply, inflammation and microglial activation following ischemic brain injury
      has been increasingly recognized to be a key contributor to the pathophysiology
      of cerebrovascular disease. However, our understanding of the cross talk between
      the ischemic brain and the immune system is limited. Recently, we demonstrated
      that following focal ischemia, death of mature viable neurons can be executed
      through phagocytosis by microglial cells or recruited macrophages, i.e. through
      phagoptosis. It was shown that inhibition of phagocytic signaling pathways
      following endothelin-1 induced focal cerebral ischemia leads to increased
      neuronal survival and neurological recovery. This suggests that inhibition of
      specific phagocytic pathways may prevent neuronal death during cerebral ischemia.
      To further explore this potential therapeutic target, we propose to assess the
      role of phagocytosis in an established model of temporary (45min) middle cerebral
      artery occlusion (tMCAo), and to evaluate neuronal survival and neurological
      recovery in mice with deficient phagocytosis. The primary outcome of this study
      will be forelimb function assessed with the staircase test. Secondary outcomes
      constitute Rotarod performance, stroke volume (quantified on MR imaging or brain
      sections, respectively), diffusion tensor imaging (DTI) connectome mapping, and
      histological analyses to measure neuronal and microglial densities, and
      phagocytic activity. Male mice aged 10-12 weeks will be used for experiments.

PMID- 29184654
TI  - On the need for multi-scale geometric modelling of the mitral heart valve.

PMID- 29184655
TI  - Editorial: Challenges for the usability of AR and VR for clinical neurosurgical
      procedures.
AB  - There are a number of challenges that must be faced when trying to develop AR and
      VR-based Neurosurgical simulators, Surgical Navigation Platforms, and "Smart OR"
      systems. Trying to simulate an operating room environment and surgical tasks in
      Augmented and Virtual Reality is a challenge many are attempting to solve, in
      order to train surgeons or help them operate. What are some of the needs of the
      surgeon, and what are the challenges encountered (human computer interface,
      perception, workflow, etc). We discuss these tradeoffs and conclude with critical
      remarks.

PMID- 29184656
TI  - Multimodal connectivity based eloquence score computation and visualisation for
      computer-aided neurosurgical path planning.
AB  - Non-invasive assessment of cognitive importance has been a major challenge for
      planning of neurosurgical procedures. In the past decade, in vivo brain imaging
      modalities have been considered for estimating the 'eloquence' of brain areas. In
      order to estimate the impact of damage caused by an access path towards a target
      region inside of the skull, multi-modal metrics are introduced in this paper.
      Accordingly, this estimated damage is obtained by combining multi-modal metrics.
      In other words, this damage is an aggregate of intervened grey matter volume and
      axonal fibre numbers, weighted by their importance within the assigned anatomical
      and functional networks. To validate these metrics, an exhaustive search
      algorithm is implemented for characterising the solution space and visually
      representing connectional cost associated with a path initiated from underlying
      points. In this presentation, brain networks are built from resting state
      functional magnetic resonance imaging (fMRI) and deterministic tractography.
      their results demonstrate that the proposed approach is capable of refining
      traditional heuristics, such as choosing the minimal distance from the lesion, by
      supplementing connectional importance of the resected tissue. This provides
      complementary information to help the surgeon in avoiding important functional
      hubs and their anatomical linkages; which are derived from neuroimaging
      modalities and incorporated to the related anatomical landmarks.

PMID- 29184657
TI  - Hand-eye calibration using a target registration error model.
AB  - Surgical cameras are prevalent in modern operating theatres and are often used as
      a surrogate for direct vision. Visualisation techniques (e.g. image fusion) made
      possible by tracking the camera require accurate hand-eye calibration between the
      camera and the tracking system. The authors introduce the concept of 'guided hand
      eye calibration', where calibration measurements are facilitated by a target
      registration error (TRE) model. They formulate hand-eye calibration as a
      registration problem between homologous point-line pairs. For each measurement,
      the position of a monochromatic ball-tip stylus (a point) and its projection onto
      the image (a line) is recorded, and the TRE of the resulting calibration is
      predicted using a TRE model. The TRE model is then used to guide the placement of
      the calibration tool, so that the subsequent measurement minimises the predicted
      TRE. Assessing TRE after each measurement produces accurate calibration using a
      minimal number of measurements. As a proof of principle, they evaluated guided
      calibration using a webcam and an endoscopic camera. Their endoscopic camera
      results suggest that millimetre TRE is achievable when at least 15 measurements
      are acquired with the tracker sensor ~80 cm away on the laparoscope handle for a
      target ~20 cm away from the camera.

PMID- 29184658
TI  - Real-time geometry-aware augmented reality in minimally invasive surgery.
AB  - The potential of augmented reality (AR) technology to assist minimally invasive
      surgery (MIS) lies in its computational performance and accuracy in dealing with
      challenging MIS scenes. Even with the latest hardware and software technologies,
      achieving both real-time and accurate augmented information overlay in MIS is
      still a formidable task. In this Letter, the authors present a novel real-time AR
      framework for MIS that achieves interactive geometric aware AR in endoscopic
      surgery with stereo views. The authors' framework tracks the movement of the
      endoscopic camera and simultaneously reconstructs a dense geometric mesh of the
      MIS scene. The movement of the camera is predicted by minimising the re
      projection error to achieve a fast tracking performance, while the three
      dimensional mesh is incrementally built by a dense zero mean normalised cross
      correlation stereo-matching method to improve the accuracy of the surface
      reconstruction. The proposed system does not require any prior template or pre
      operative scan and can infer the geometric information intra-operatively in real
      time. With the geometric information available, the proposed AR framework is able
      to interactively add annotations, localisation of tumours and vessels, and
      measurement labelling with greater precision and accuracy compared with the state
      of-the-art approaches.

PMID- 29184660
TI  - Robust head CT image registration pipeline for craniosynostosis skull correction
      surgery.
AB  - Craniosynostosis is a congenital malformation of the infant skull typically
      treated via corrective surgery. To accurately quantify the extent of deformation
      and identify the optimal correction strategy, the patient-specific skull model
      extracted from a pre-surgical computed tomography (CT) image needs to be
      registered to an atlas of head CT images representative of normal subjects. Here,
      the authors present a robust multi-stage, multi-resolution registration pipeline
      to map a patient-specific CT image to the atlas space of normal CT images. The
      proposed registration pipeline first performs an initial optimisation at very low
      resolution to yield a good initial alignment that is subsequently refined at high
      resolution. They demonstrate the robustness of the proposed method by evaluating
      its performance on 560 head CT images of 320 normal subjects and 240
      craniosynostosis patients and show a success rate of 92.8 and 94.2%,
      respectively. Their method achieved a mean surface-to-surface distance between
      the patient and template skull of <2.5 mm in the targeted skull region across
      both the normal subjects and patients.

PMID- 29184659
TI  - Multi-modal imaging, model-based tracking, and mixed reality visualisation for
      orthopaedic surgery.
AB  - Orthopaedic surgeons are still following the decades old workflow of using dozens
      of two-dimensional fluoroscopic images to drill through complex 3D structures,
      e.g. pelvis. This Letter presents a mixed reality support system, which
      incorporates multi-modal data fusion and model-based surgical tool tracking for
      creating a mixed reality environment supporting screw placement in orthopaedic
      surgery. A red-green-blue-depth camera is rigidly attached to a mobile C-arm and
      is calibrated to the cone-beam computed tomography (CBCT) imaging space via
      iterative closest point algorithm. This allows real-time automatic fusion of
      reconstructed surface and/or 3D point clouds and synthetic fluoroscopic images
      obtained through CBCT imaging. An adapted 3D model-based tracking algorithm with
      automatic tool segmentation allows for tracking of the surgical tools occluded by
      hand. This proposed interactive 3D mixed reality environment provides an
      intuitive understanding of the surgical site and supports surgeons in quickly
      localising the entry point and orienting the surgical tool during screw
      placement. The authors validate the augmentation by measuring target registration
      error and also evaluate the tracking accuracy in the presence of partial
      occlusion.

PMID- 29184661
TI  - Application of an RGBD augmented C-arm for minimally invasive scoliosis surgery
      assistance.
AB  - Minimally invasive surgeries (MISs) are gaining popularity as alternatives to
      conventional open surgeries. In thoracoscopic scoliosis MIS, fluoroscopy is used
      to guide pedicle screw placement and to visualise the effect of the intervention
      on the spine curvature. However, cosmetic external appearance is the most
      important concern for patients, while correction of the spine and achieving
      coronal and sagittal trunk balance are the top priorities for surgeons. The
      authors present the feasibility study of the first intra-operative assistive
      system for scoliosis surgery composed of a single RGBD camera affixed on a C-arm
      which allows visualising in real time the surgery effects on the patient trunk
      surface in the transverse plane. They perform three feasibility experiments from
      simulated data based on scoliotic patients to live acquisition from non-scoliotic
      mannequin and person, all showing that the proposed system accuracy is comparable
      with scoliotic surface reconstruction state of art.

PMID- 29184662
TI  - Towards X-ray free endovascular interventions - using HoloLens for on-line
      holographic visualisation.
AB  - A major challenge during endovascular interventions is visualising the position
      and orientation of the catheter being inserted. This is typically achieved by
      intermittent X-ray imaging. Since the radiation exposure to the surgeon is
      considerable, it is desirable to reduce X-ray exposure to the bare minimum
      needed. Additionally, transferring two-dimensional (2D) X-ray images to 3D
      locations is challenging. The authors present the development of a real-time
      navigation framework, which allows a 3D holographic view of the vascular system
      without any need of radiation. They extract the patient's surface and vascular
      tree from pre-operative computed tomography data and register it to the patient
      using a magnetic tracking system. The system was evaluated on an anthropomorphic
      full-body phantom by experienced clinicians using a four-point questionnaire. The
      average score of the system (maximum of 20) was found to be 17.5. The authors'
      approach shows great potential to improve the workflow for endovascular
      procedures, by simultaneously reducing X-ray exposure. It will also improve the
      learning curve and help novices to more quickly master the required skills.

PMID- 29184663
TI  - Quantifying attention shifts in augmented reality image-guided neurosurgery.
AB  - Image-guided surgery (IGS) has allowed for more minimally invasive procedures,
      leading to better patient outcomes, reduced risk of infection, less pain, shorter
      hospital stays and faster recoveries. One drawback that has emerged with IGS is
      that the surgeon must shift their attention from the patient to the monitor for
      guidance. Yet both cognitive and motor tasks are negatively affected with
      attention shifts. Augmented reality (AR), which merges the realworld surgical
      scene with preoperative virtual patient images and plans, has been proposed as a
      solution to this drawback. In this work, we studied the impact of two different
      types of AR IGS set-ups (mobile AR and desktop AR) and traditional navigation on
      attention shifts for the specific task of craniotomy planning. We found a
      significant difference in terms of the time taken to perform the task and
      attention shifts between traditional navigation, but no significant difference
      between the different AR set-ups. With mobile AR, however, users felt that the
      system was easier to use and that their performance was better. These results
      suggest that regardless of where the AR visualisation is shown to the surgeon, AR
      may reduce attention shifts, leading to more streamlined and focused procedures.

PMID- 29184664
TI  - Estimation of surgical tool-tip tracking error distribution in coordinate
      reference frame involving pivot calibration uncertainty.
AB  - Accurate understanding of surgical tool-tip tracking error is important for
      decision making in image-guided surgery. In this Letter, the authors present a
      novel method to estimate/model surgical tool-tip tracking error in which they
      take pivot calibration uncertainty into consideration. First, a new type of error
      that is referred to as total target registration error (TTRE) is formally defined
      in a single-rigid registration. Target localisation error (TLE) in two spaces to
      be registered is considered in proposed TTRE formulation. With first-order
      approximation in fiducial localisation error (FLE) or TLE magnitude, TTRE
      statistics (mean, covariance matrix and root-mean-square (RMS)) are then derived.
      Second, surgical tool-tip tracking error in optical tracking system (OTS) frame
      is formulated using TTRE when pivot calibration uncertainty is considered.
      Finally, TTRE statistics of tool-tip in OTS frame are then propagated relative to
      a coordinate reference frame (CRF) rigid-body. Monte Carlo simulations are
      conducted to validate the proposed error model. The percentage passing
      statistical tests that there is no difference between simulated and theoretical
      mean and covariance matrix of tool-tip tracking error in CRF space is more than
      90% in all test cases. The RMS percentage difference between simulated and
      theoretical tool-tip tracking error in CRF space is within 5% in all test cases.

PMID- 29184665
TI  - Distance sonification in image-guided neurosurgery.
AB  - Image-guided neurosurgery, or neuronavigation, has been used to visualise the
      location of a surgical probe by mapping the probe location to pre-operative
      models of a patient's anatomy. One common limitation of this approach is that it
      requires the surgeon to divert their attention away from the patient and towards
      the neuronavigation system. In order to improve this type of application, the
      authors designed a system that sonifies (i.e. provides audible feedback of)
      distance information between a surgical probe and the location of the anatomy of
      interest. A user study (n = 15) was completed to determine the utility of
      sonified distance information within an existing neuronavigation platform
      (Intraoperative Brain Imaging System (IBIS) Neuronav). The authors' results were
      consistent with the idea that combining auditory distance cues with existing
      visual information from image-guided surgery systems may result in greater
      accuracy when locating specified points on a pre-operative scan, thereby
      potentially reducing the extent of the required surgical openings, as well as
      potentially increasing the precision of individual surgical tasks. Further, the
      authors' results were also consistent with the hypothesis that combining auditory
      and visual information reduces the perceived difficulty in locating a target
      location within a three-dimensional volume.

PMID- 29184667
TI  - Design and evaluation of an augmented reality simulator using leap motion.
AB  - Advances in virtual and augmented reality (AR) are having an impact on the
      medical field in areas such as surgical simulation. Improvements to surgical
      simulation will provide students and residents with additional training and
      evaluation methods. This is particularly important for procedures such as the
      endoscopic third ventriculostomy (ETV), which residents perform regularly.
      Simulators such as NeuroTouch, have been designed to aid in training associated
      with this procedure. The authors have designed an affordable and easily
      accessible ETV simulator, and compare it with the existing NeuroTouch for its
      usability and training effectiveness. This simulator was developed using Unity,
      Vuforia and the leap motion (LM) for an AR environment. The participants, 16
      novices and two expert neurosurgeons, were asked to complete 40 targeting tasks.
      Participants used the NeuroTouch tool or a virtual hand controlled by the LM to
      select the position and orientation for these tasks. The length of time to
      complete each task was recorded and the trajectory log files were used to
      calculate performance. The resulting data from the novices' and experts' speed
      and accuracy are compared, and they discuss the objective performance of training
      in terms of the speed and accuracy of targeting accuracy for each system.

PMID- 29184666
TI  - Intra-operative ultrasound-based augmented reality guidance for laparoscopic
      surgery.
AB  - In laparoscopic surgery, the surgeon must operate with a limited field of view
      and reduced depth perception. This makes spatial understanding of critical
      structures difficult, such as an endophytic tumour in a partial nephrectomy. Such
      tumours yield a high complication rate of 47%, and excising them increases the
      risk of cutting into the kidney's collecting system. To overcome these
      challenges, an augmented reality guidance system is proposed. Using intra
      operative ultrasound, a single navigation aid, and surgical instrument tracking,
      four augmentations of guidance information are provided during tumour excision.
      Qualitative and quantitative system benefits are measured in simulated robot
      assisted partial nephrectomies. Robot-to-camera calibration achieved a total
      registration error of 1.0 +/- 0.4 mm while the total system error is 2.5 +/- 0.5
      mm. The system significantly reduced healthy tissue excised from an average (+/
      standard deviation) of 30.6 +/- 5.5 to 17.5 +/- 2.4 cm3 (p < 0.05) and reduced
      the depth from the tumor underside to cut from an average (+/-standard deviation)
      of 10.2 +/- 4.1 to 3.3 +/- 2.3 mm (p < 0.05). Further evaluation is required in
      vivo, but the system has promising potential to reduce the amount of healthy
      parenchymal tissue excised.

PMID- 29184668
TI  - Can surgical simulation be used to train detection and classification of neural
      networks?
AB  - Computer-assisted interventions (CAI) aim to increase the effectiveness,
      precision and repeatability of procedures to improve surgical outcomes. The
      presence and motion of surgical tools is a key information input for CAI surgical
      phase recognition algorithms. Vision-based tool detection and recognition
      approaches are an attractive solution and can be designed to take advantage of
      the powerful deep learning paradigm that is rapidly advancing image recognition
      and classification. The challenge for such algorithms is the availability and
      quality of labelled data used for training. In this Letter, surgical simulation
      is used to train tool detection and segmentation based on deep convolutional
      neural networks and generative adversarial networks. The authors experiment with
      two network architectures for image segmentation in tool classes commonly
      encountered during cataract surgery. A commercially-available simulator is used
      to create a simulated cataract dataset for training models prior to performing
      transfer learning on real surgical data. To the best of authors' knowledge, this
      is the first attempt to train deep learning models for surgical instrument
      detection on simulated data while demonstrating promising results to generalise
      on real data. Results indicate that simulated data does have some potential for
      training advanced classification methods for CAI systems.

PMID- 29184670
TI  - The era of a "liquid biopsy" may be on the horizon in non-small cell lung cancer.

PMID- 29184669
TI  - Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels
      in humans safely and sustainably: a randomized, double-blind, placebo-controlled
      study.
AB  - NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine
      dinucleotide (NAD+) precursor vitamin found in milk, and pterostilbene (PT), a
      polyphenol found in blueberries. Here, we report this first-in-humans clinical
      trial designed to assess the safety and efficacy of a repeat dose of NRPT
      (commercially known as Basis). NRPT was evaluated in a randomized, double-blind,
      and placebo-controlled study in a population of 120 healthy adults between the
      ages of 60 and 80 years. The study consisted of three treatment arms: placebo,
      recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All
      subjects took their blinded supplement daily for eight weeks. Analysis of NAD+ in
      whole blood demonstrated that NRPT significantly increases the concentration of
      NAD+ in a dose-dependent manner. NAD+ levels increased by approximately 40% in
      the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as
      compared to placebo and baseline. Furthermore, this significant increase in NAD+
      levels was sustained throughout the entire 8-week trial. NAD+ levels did not
      increase for the placebo group during the trial. No serious adverse events were
      reported in this study. This study shows that a repeat dose of NRPT is a safe and
      effective way to increase NAD+ levels sustainably.

PMID- 29184671
TI  - Urine test for EGFR analysis in patients with non-small cell lung cancer.
AB  - Precision medicine approaches in oncology are reliant on the accurate genomic
      characterization of tumors. While tissue remains the mainstay specimen for
      molecular testing, tumor biopsies are riddled with challenges and limitations due
      to their invasive and site-specific nature. Tumor inaccessibility and
      intratumoral heterogeneity, in particular, represent significant obstacles to the
      identification of actionable genetic alterations and hence effective mono- and
      combination therapy strategies. Proof-of-concept studies indicate that
      circulating tumor DNA (ctDNA) released from multiple tumor regions and anatomical
      locations is more reflective of intra- and intertumoral heterogeneity. Non
      invasive liquid biopsy approaches that allow for the analysis of ctDNA are thus
      being increasingly implemented in routine patient care for the detection and
      monitoring of cancer-associated mutations. Indeed, the use of plasma testing to
      screen for epidermal growth factor receptor (EGFR) T790M mutant positive non
      small cell lung cancer (NSCLC) patients eligible for treatment with third
      generation EGFR inhibitors was recently approved by the U.S. Food and Drug
      Administration and is incorporated into the most recent version of the National
      Comprehensive Cancer Center guidelines as an alternative to tissue biopsy. Urine
      represents another liquid biopsy specimen that is distinguished by its ease of
      collection, option for home collection, and lack of temporal and volumetric
      collection restrictions. Importantly, there is an accumulating body of evidence
      supporting the clinical validity of urinary EGFR mutant testing for the
      identification and stratification of patients likely to benefit from EGFR
      directed therapies and as a means to assess patient response, the presence of
      residual disease, and emergence of resistant tumor cell populations.

PMID- 29184673
TI  - Critical issues in the clinical application of liquid biopsy in non-small cell
      lung cancer.
AB  - Current therapeutic options for non-small cell lung cancer (NSCLC) patients are
      chemotherapy and targeted therapy directed mainly against epidermal growth factor
      receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements.
      Targeted therapy relies on the availability of tumor biopsies for molecular
      profiling at diagnosis and to longitudinally monitor treatment response and
      resistance development. Unfortunately, tumor biopsy might be invasive, recover
      poor material of suboptimal quality, and cause sample bias due to tumor
      heterogeneity. Many studies have illustrated the potential of liquid biopsy as
      minimal invasive approach to respond to the urgent need for real time monitoring,
      stratification, and personalized optimized treatment in NSCLC patients. In
      principle, the liquid biopsy could provide the genetic landscape of primary and
      metastatic cancerous lesions, detecting "druggable" genomic alterations or
      associated with treatment resistance. Moreover, it would guarantee the
      prognostic/predictive biomarkers evaluation in patients for whom biopsies are
      inaccessible or difficult to repeat. At this regard, the prognostic value of
      circulating tumor cells (CTCs) in NSCLC patients has been largely investigated,
      but still their clinical utility as tumor biomarker is hampered by the lack of a
      consensus on the criteria necessary and sufficient to define them and on the
      standard operating procedures (SOPs) for their assessment. This review will
      summarize current developments on liquid biopsy in NSCLC, addressing the
      technology issues that contribute to the poor ability to track CTCs in the blood
      of NSCLC patients, thus limiting their extensive use in the clinical practice,
      and analyzing the solutions adopted to overcome such limits, on the road towards
      the clinical validation.

PMID- 29184672
TI  - New insights in non-small-cell lung cancer: circulating tumor cells and cell-free
      DNA.
AB  - Lung cancer is the second most frequent tumor and the leading cause of death by
      cancer in both men and women. Increasing knowledge about the cancer genome and
      tumor environment has led to a new setting in which morphological and molecular
      characterization is needed to treat patients in the most personalized way in
      order to achieve better outcomes. Since tumor products can be detected in body
      fluids, the liquid biopsy, particularly, peripheral blood, has emerged as a new
      source for lung cancer biomarker's analysis. A variety of tumor components can be
      used for this purpose. Among them, circulating tumor cells (CTCs) and circulating
      tumor DNA (ctDNA) should be especially considered. Different detection methods
      for both CTCs and ctDNA have been and are being developed to improve the
      sensitivity and specificity of these tests. This would lead to better
      characterization and would solve some clinical doubts at different disease
      evolution times, e.g., intratumoral or temporal heterogeneity, difficulty in the
      obtaining a tumor sample, etc., and would also avoid the side effects of very
      expensive and complicated tumor obtaining interventions. CTCs and ctDNA are
      useful in different lung cancer settings. Their value has been shown for the
      early diagnosis, prognosis, prediction of treatment efficacy, monitoring
      responses and early detection of lung cancer relapse. CTCs have still not been
      validated for use in clinical settings in non-small-cell lung cancer (NSCLC),
      while ctDNA has been approved by the Food and Drug Administration (FDA) and
      European Medical Association (EMA), and the main clinical guidelines used for
      detect different epidermal growth factor receptor (EGFR) mutations and the
      monitoring and treatment choice of mutated patients with tyrosine kinase
      inhibitors (TKIs). This review, describes how ctDNA seem to be winning the race
      against CTCs from the laboratory bench to clinical practice due to easier
      obtaining methods, manipulation and its implementation into clinical practice.

PMID- 29184674
TI  - Molecular characterization and prognostic significance of circulating tumor cells
      in patients with non-small cell lung cancer.
AB  - Circulating tumor cells (CTCs) are rare epithelial cells that can be found in the
      peripheral blood of cancer patients. A growing body of evidence indicates that
      CTCs may play a role in non-small cell lung cancer (NSCLC) for diagnosis, therapy
      monitoring and prognostic purposes. CTCs evaluation could be particularly
      relevant in this clinical setting, considering that physicians often have
      difficulty in obtaining an adequate tumor tissue and that patients are not always
      suitable to receive a re-biopsy. In the current review, we will focus on the
      molecular characterization and prognostic significance of CTCs in NSCLC patients.

PMID- 29184676
TI  - Exosomes as diagnostic and predictive biomarkers in lung cancer.
AB  - The concept of exosomes has evolved from be considered garbage bags to the
      demonstration that exosomes could play very interesting roles and functions, from
      biomarkers detection to the potential of work as drug delivery systems. It has
      been widely proved that exosomes can contain key molecules important for the
      tumour development. The current review summarizes the latest investigations
      developed in the field of predictive exosomal biomarkers. The microRNAs (miRNAs)
      are the more known molecules due to their amount inside the exosomes and the
      sensitivity of the techniques available for their study. However, exosomal
      proteins, RNA and DNA are becoming an interesting and more feasible field of
      study due to the improvement in the techniques available for their analysis. In
      the future years, it is hoped that exosomes will become an established member of
      the liquid biopsies in the clinical practice due to their diagnostic and
      prognostic properties.

PMID- 29184675
TI  - Possible application of circulating free tumor DNA in non-small cell lung cancer
      patients.
AB  - Liquid biopsies have been heralded as a game changer in cancer management. Blood
      tests offer a minimally invasive, safe and sensitive complementary (or even
      alternative) approach for tissue biopsies. With lung cancer being the second most
      commonly diagnosed cancer and the leading cause of cancer deaths worldwide, due
      to the limitations of tissue sampling, liquid biopsies must urgently materialize
      in the clinic. In this short review, we will present the current applications of
      cell-free DNA (cfDNA) in lung cancer management, emphasizing on our own
      experience and previous work. We will also shortly comment on the challenges and
      need for a coordinated collaboration combining disciplines and sectors (from
      academia to health economies) in order to accelerate liquid biopsy development in
      lung cancer and other cancers.

PMID- 29184677
TI  - Cell free DNA analysis by SiRe(r) next generation sequencing panel in non small
      cell lung cancer patients: focus on basal setting.
AB  - Background: Non small cell lung cancer (NSCLC) is diagnosed in most cases on
      small tissue samples, such as cytological preparations and histological biopsies;
      these limited tissue specimens may be not always sufficient for testing epidermal
      growth factor receptor (EGFR) mutations and other relevant predictive biomarkers.
      Cell-free DNA (cfDNA) can be used as a surrogate for EGFR mutational testing,
      whenever tissue is unavailable. However, the detection of gene mutations on cfDNA
      is challenging; in fact, the extremely low concentration of circulating tumor DNA
      requires the implementation of highly sensitive and validated next generation
      techniques. Methods: Thus, we have recently validated a novel next generation
      sequencing (NGS) assay, employing the SiRe(r) gene panel to detect on cfDNA
      mutations of EGFR and KRAS, NRAS, BRAF, cKIT and PDGFR genes. In this current
      study, we report on a series of NSCLC patients, without available tissue for EGFR
      testing, who prospectively underwent SiRe(r) NGS analysis. Results: The results
      confirm the high clinical performance, in terms of success rate and mutation
      detection, of NGS based analysis of cfDNA. Conclusions: SiRe(r) NGS panel
      represent an effective diagnostic tool in cfDNA analysis setting.

PMID- 29184678
TI  - Liquid biopsy for monitoring anaplastic lymphoma kinase inhibitors in non-small
      cell lung cancer: two cases compared.
AB  - Three to seven percent of non-small cell lung cancer (NSCLC) patients show
      anaplastic lymphoma kinase (ALK)-translocation and could be treated with ALK
      inhibitors. However, under crizotinib, a first-generation ALK-inhibitor, patients
      develop drug resistance after a median of 12 months. To overcome crizotinib
      resistance, several next-generation ALK inhibitors have been developed. In NSCLC,
      liquid biopsy allowed important improvements in the detection of the epidermal
      growth factor receptor (EGFR) mutation. The ability of liquid biopsy to detect
      oncogenic gene/protein fusions is a newly investigated field, and is not
      routinely applied yet. We here present two NSCLC patients, both rearranged for
      echinoderm microtubule associated-protein like 4-anaplastic lymphoma kinase (EML4
      ALK) and treated accordingly, who differed in the clinical outcome. We analyzed
      the predictive value of the liquid biopsy components, namely epithelial cellular
      adhesion molecule (EpCAM)+ circulating tumor cells (CTCs), EpCAM low/neg CTCs,
      EML4-ALK rearranged CTCs, and cell-free mRNA (cfmRNA), during ALK-inhibitors
      treatment. This analysis showed a potential association between the liquid biopsy
      biomarkers, patients' outcome and response to treatment, thus suggesting their
      combined use in the clinical practice, as proposed here. This approach would
      allow longitudinal monitoring and consequent identification of putative drug
      resistance mechanisms, in the light of improving high-risk patient management.

PMID- 29184679
TI  - Outcomes of adjuvant radiotherapy and lymph node resection in elderly patients
      with pancreatic cancer treated with surgery and chemotherapy.
AB  - Background: We sought to determine the effects of post-operative radiation
      therapy (PORT) and lymph node resection (LNR) on survival in patients >=70 years
      with pancreatic cancer treated with surgery and chemotherapy. Methods: An
      analysis of patients >=70 years with surgically resected pancreatic cancer who
      received chemotherapy from the SEER database between 2004-2008 was performed to
      determine association of PORT and LNR on survival. Results: We identified 961
      patients who met inclusion criteria. There was a trend towards increased survival
      associated with PORT in all patients (P=0.052) and N1 patients (P=0.060) but no
      benefit in N0 patients (P=0.161). There was no difference in OS based on number
      of lymph nodes removed in all (P=0.741), N0 (P=0.588), and N1 (P=0.070) patients.
      MVA for all patients revealed that higher T stage, N1, and high grade tumors were
      prognostic for increased mortality, while there was decreased mortality with PORT
      and mild benefit with increased lymph nodes resected (P=0.084). Conclusions: PORT
      demonstrated no benefit in survival of pancreatic cancer patients >=70 who are
      resected and treated with adjuvant chemotherapy. Future investigation will need
      to address age as a stratification factor for pancreatic cancer in the adjuvant
      setting.

PMID- 29184680
TI  - Stereotactic body radiotherapy for locally-advanced unresectable pancreatic
      cancer-patterns of care and overall survival.
AB  - Background: Unresectable pancreatic cancer remains a challenging disease to
      treat. Stereotactic body radiotherapy (SBRT) allows for a higher biologically
      equivalent dose in an abbreviated course more convenient for patients and the
      integration of systemic therapy. We sought to investigate utilization trends and
      survival outcomes for patients treated with pancreatic SBRT versus conventionally
      fractionated radiotherapy (CFRT). Methods: We engaged the National Cancer
      Database (NCDB) from 1998-2012 and identified locally-advanced unresectable
      patients with histologically confirmed, non-metastatic, pancreatic adenocarcinoma
      who received radiotherapy. Patients who received CFRT (1.5-4.0 Gy per fraction to
      a dose of >=45 Gy, n=11,879) were compared to those who received SBRT (6-15 Gy
      per fraction to a dose of >=20 Gy, n=474). Results: Median follow-up was 11.0
      months (18.4 months for survivors). SBRT utilization increased from 0.2% to 7.4%
      from 1998 to 2012 (P<0.05). On multivariable analysis, factors predictive for
      preferential utilization of SBRT over CFRT were later year of diagnosis, age >=75
      years, increased facility volume, and no chemotherapy in the initial treatment
      plan. Unadjusted median survival was 11.2 months for CFRT vs. 12.6 months for
      SBRT (P=0.002). Results were consistent in the propensity matched model.
      Variables predictive for improved survival on multivariable analysis were
      diagnosis after 2010, younger age, lower comorbidity score, tumor size <3 cm,
      nodal stage zero, and receipt of chemotherapy (P<0.05). Conclusions: SBRT
      utilization has increased significantly and is associated with a small absolute
      improvement in overall survival (OS) compared to CFRT. The decreased treatment
      time, without apparent compromise in survival, makes SBRT an attractive option
      for patients with unresectable pancreatic cancer warranting further research.

PMID- 29184681
TI  - Prognostic impact of carbohydrate antigen 19-9 level at diagnosis in resected
      stage I-III pancreatic adenocarcinoma: a U.S. population study.
AB  - Background: Pancreatic adenocarcinoma is a highly aggressive cancer, with
      surgical resection and systemic therapy offering the only hope for long-term
      survival. Carbohydrate antigen 19-9 (CA 19-9) has been used as a prognostic
      marker after resection; however, the relationship between survival and pre
      treatment CA 19-9 level remains unclear. This study evaluates pre-treatment serum
      CA 19-9 level as a predictor for long-term survival. Methods: The U.S. National
      Cancer Data Base [2004-2012] was reviewed for patients with clinical stages I-III
      resected pancreatic adenocarcinoma with recorded pre-treatment CA 19-9 levels
      (U/mL). Kaplan Meier and Weibull survival analyses were performed. Results: Four
      thousand seven hundred and one patients were included: 12.6% received neoadjuvant
      therapy (NAT), 27.4% underwent surgery, and 60.1% underwent surgery and adjuvant
      therapy. Amongst those who underwent initial surgery, there was no association
      between CA 19-9 levels <=800 (<=100, 101-300, 301-500, 501-800) with survival
      (stage I P=0.7592, stage II P=0.5088, stage III P=0.9037). Levels >800 were
      associated with significantly worse survival in all stages (P<=0.0001, all).
      Amongst those who received NAT, levels >800 were associated with worse survival
      in early (stage I P=0.0001), but not advanced stage disease (stage II P=0.1891,
      stage III P=0.9316). In multivariable analyses, levels >800 demonstrated a 3.29
      greater hazard of mortality with respect to patients with levels <=100
      (P<0.0001). Conclusions: Pre-treatment CA 19-9 levels >800 appear to be
      associated with advanced disease, and are negatively associated with long-term
      survival. However, levels <=800 had no significant association with survival.
      Although this study suggests an association, further study is needed to evaluate
      whether patients with CA 19-9 levels >800 benefit from NAT.

PMID- 29184682
TI  - Survival differences among patients with hepatocellular carcinoma based on the
      stage of disease and therapy received: pre and post sorafenib era.
AB  - Background: The incidence of hepatocellular carcinoma (HCC) is increasing.
      Development of newer therapeutic modalities has changed the paradigm of HCC
      treatment in recent years. So, the aim of our study is to analyze the impact of
      these treatment modalities into the survival of HCC patients, based on the stage
      of HCC in real life practice. Methods: We analyzed the data from the SEER
      database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted
      Louisiana Cases, Nov 2015 Sub (1973-2013 varying). Relative survival rates (RSRs)
      and hazard ratios (HRs) were measured for patients diagnosed with HCC between
      2001 and 2013. Rates were compared between pre sorafenib [2001-2007] and post
      sorafenib [2008-2013] eras. Results: A total of 50,088 patients (21,435 in pre
      sorafenib era and 28,653 in the post-sorafenib era) were included with HCC from
      SEER database. The median relative survival for the entire population was 14
      months with 5-year RSR of 21.20%; 11 months for those diagnosed in 2001-2007 with
      5-year RSR 19.30% and 17 months for those diagnosed in 2008-2013 with 5-year RSR
      22.40% (P<0.01). This survival improvement was largely limited to HCC patients
      with single nodule (5-year RSR; 35.1% vs. 37.00% for pre and post sorafenib era
      respectively; P value <0.01) and multiple nodules without vascular invasion (5
      year RSR; 19.90% vs. 22.60% for pre and post sorafenib era respectively; P value
      <0.01). RSR remained extremely poor with no significant improvement for advanced
      stage HCC who had vascular invasion (P=0.37) or distant metastasis (P=0.10),
      respectively for pre and post sorafenib era in each category. Survival improved
      since 2008, for HCC patients who received either no surgical intervention
      (P<0.01) or received tumor-directed therapy (P<0.01), however, it remained
      significantly poor compared to the patients who received lobectomy or hepatectomy
      and transplant. Approximately 70% of patients from our study population did not
      receive any HCC directed surgical intervention and among this, more than 40% of
      patients were with single nodule in the liver. Conclusions: Survival in patients
      with HCC has improved since 2008, which is limited to early stage HCC. Survival
      of advanced stage HCC patients is extremely poor and has not shown any
      significant improvement since the approval of sorafenib, emphasizing the need for
      better therapeutic options. Not receiving any surgical intervention is associated
      with significantly poor prognosis. Large numbers of early stage HCC patients were
      not able to receive surgical interventions. This can impose a significant
      financial burden, as these patients would progress on to the advanced stage,
      where treatment options are very limited and not as cost-effective. This
      emphasizes the need for further research to identify various barriers and the
      possible need for healthcare policy changes.

PMID- 29184683
TI  - Selective internal radiation therapy using yttrium-90 resin microspheres in
      patients with unresectable hepatocellular carcinoma: a retrospective study.
AB  - Background: Selective internal radiation therapy (SIRT) with yttrium-90 resin (Y
      90 resin) microspheres has been used as a locoregional therapy for patients with
      unresectable hepatocellular carcinoma (HCC). We examined patient and disease
      characteristics that might affect survival after Y-90 resin, as well as treatment
      tolerability. Methods: Data from patients with unresectable HCC treated with Y-90
      resin at a single institution were reviewed retrospectively. Survival was
      assessed with Kaplan-Meier curves and log-rank tests. Response was evaluated with
      the response evaluation criteria in solid tumors (RECIST) criteria. Adverse
      events (AEs) were noted, and laboratory values were graded with CTCAE v3.0.
      Results: Data from 111 patients were analyzed. AEs occurred in 23 patients at 1
      week after treatment and in 46 at 3 months. At 6 months, 13 patients had a
      complete response and 13 had a partial response. Factors associated with longer
      overall survival (OS) included early-stage disease [27.8 months for patients with
      Barcelona-Clinic Liver Cancer (BCLC) A vs. 9.2 months for BCLC C]; treatment with
      other locoregional therapies (69.0 vs. 11.4 months); and lack of bilobar disease
      (23.5 vs. 9.4 months), portal vein thrombosis (16.2 vs. 8.6 months), ascites
      (16.6 vs. 10.3 months), and treatment with sorafenib (17.2 vs. 10.3 months). In
      six patients, Y-90 resin was used as a bridge to liver transplantation, which
      greatly improved survival (69.0 vs. 12.1 months). Conclusions: Several
      characteristics may prove useful for selecting patients likely to respond well to
      Y-90 resin. These results should be confirmed in prospective studies.

PMID- 29184684
TI  - Impact of sarcopenia on outcomes of locally advanced esophageal cancer patients
      treated with neoadjuvant chemoradiation followed by surgery.
AB  - Background: Sarcopenia is an independent predictor of clinical outcomes in
      multiple gastrointestinal cancers. Total psoas area (TPA), as measured on a
      single cross-sectional CT image at the L4 vertebral body level, has been
      correlated with sarcopenia. We sought to evaluate whether TPA was predictive of
      acute grade >=3 toxicity, pathologic response, and overall survival in patients
      with locally advanced esophageal cancer receiving tri-modality therapy. Methods:
      An institutional database of esophageal cancer patients treated with neoadjuvant
      chemoradiation followed by surgery was queried. Of 77 patients treated from 2008
      to 2012 with intensity modulated radiation therapy (IMRT) and image guided
      radiation therapy (IGRT), 56 patients were eligible based on having CT imaging
      that included the L4 vertebral body. The L4 vertebra was identified on axial CT
      and the psoas muscle was manually contoured bilaterally to determine the skeletal
      muscle index. Sarcopenia was defined by the presence of the psoas area less than
      the median of the cohort. Acute toxicity was defined as within 3 months of
      radiotherapy based on Common Terminology Criteria for Adverse Events. ROC curve,
      logistic regression, and Kaplan Meier estimates were used when appropriate.
      Results: Sarcopenia was associated with increased acute grade >=3 toxicity from
      chemoradiation by ROC analysis using a cut off of 841.5 mm2/m2 (P=0.003, AUC
      0.709, sensitivity 60.9%, specificity 78.8%) and logistic regression (P=0.002).
      Patients with TPA <841.5 mm2/m2 were 5.78 times more likely to develop grade 3 or
      higher toxicity (P=0.004). Sarcopenia did not predict a difference in overall
      survival (P=0.217) and was not significant for pathologic complete response or
      favorable pathologic response (TRG 0/1). Conclusions: In our cohort of patients,
      sarcopenia was associated with a significant increase in acute grade >=3 toxicity
      with chemoradiation, suggesting a potential role for neoadjuvant patient
      selection strategies. There was no difference in pathologic response or overall
      survival.

PMID- 29184685
TI  - Adjuvant chemotherapy and outcomes in esophageal carcinoma.
AB  - Background: Standard treatment for locally advanced esophageal cancer is
      neoadjuvant chemoradiation followed by surgery. The role of postoperative
      chemotherapy is unclear. We sought to determine the indications, patterns, and
      outcomes for adjuvant chemotherapy in esophageal carcinoma. Methods: This single
      institution retrospective review included patients with esophageal cancer who
      received neoadjuvant chemoradiation and surgery at Moffitt. We identified
      patients in this cohort who additionally received adjuvant chemotherapy. Medical
      records were reviewed for demographic/clinical information. Survival was
      estimated using the Kaplan-Meier method and compared by log-rank. Case-control
      analysis was performed using a 2:1 nearest neighbor propensity score matching
      algorithm, which included 92 without adjuvant chemotherapy and 46 with adjuvant
      chemotherapy. Results: We identified 382 patients, 46 of whom received adjuvant
      chemotherapy. Patients who received adjuvant chemotherapy were younger (60.2 vs.
      63.8 years; P=0.047), more likely to have adenocarcinoma (91% vs. 85%; P=0.034),
      had more advanced ypT and ypN classifications (P<0.001), less response to
      neoadjuvant therapy (P<0.001), and more margin positivity (15% vs. 4%; P=0.007).
      With propensity score matching analysis, no variables were significantly
      different between the two matched groups. Median follow-up times for the entire
      cohort and for case-control analysis were 2.9 and 2.4 years, respectively. There
      were no significant differences in overall or recurrence-free survival (RFS)
      between groups in either analysis. Conclusions: The role of adjuvant chemotherapy
      following neoadjuvant chemoradiation and surgery in esophageal cancer is unclear.
      We found no significant difference in survival based on adjuvant chemotherapy.
      Future prospective studies should further investigate potential survival benefits
      and morbidity.

PMID- 29184687
TI  - CT-based assessment of visceral adiposity and outcomes for esophageal
      adenocarcinoma.
AB  - Background: Various methods of quantifying and correlating obesity to outcomes
      for patients with esophageal adenocarcinoma (EA) have been evaluated. Published
      data suggest that quantification of adiposity may be more accurate than body mass
      index (BMI) as a prognostic factor. We report our analysis of adiposity as a
      prognostic factor in a series of patients with EA. Methods: This single
      institution retrospective review included patients with EA who underwent
      esophagectomy from 1994-2008. Patients with BMI <20 were excluded. Using the
      preoperative CT scan, the visceral (VFA), subcutaneous (SFA), and total abdominal
      fat (TFA) areas were calculated. Each was contoured on a Siemens Leonardo
      workstation at the level of the iliac crest (L4/5). The Hounsfield threshold was 
      30 to -130. Outcomes were analyzed using Kaplan-Meier method and log-rank
      analysis. Multivariate analysis (MVA) was performed using the Cox proportion
      hazard regression model. Results: We identified 126 patients for the analysis.
      There were no statistically significant differences in overall survival or
      disease-free survival between groups above and below the medians for TFA, SFA, or
      VFA/SFA ratio. However, an increase in VFA was significantly associated with
      worsened OS and DFS when we further classified patients into quartiles. Patients
      with VFA >=182 cm2 had larger tumor size (P=0.016), fewer involved lymph nodes
      (P=0.047), longer operating times (P=0.032), and were more likely to be males
      (P=0.042). Conclusions: Published data have demonstrated an association between
      treatment outcomes and degree of adiposity; our study found a correlation between
      VFA and OS and DFS in patients with EA. Median TFA, SFA, and VFA/SFA were not
      prognostic on MVA. While VFA >182 cm2 was associated with larger tumors, there
      were also fewer lymph nodes harvested in this group.

PMID- 29184686
TI  - Survival benefit of neoadjuvant versus adjuvant radiotherapy in lymph node
      positive esophageal cancer: a population based analysis.
AB  - Background: The impact of radiotherapy on the survival of patients with locally
      advanced esophageal cancer (EC) is presently insufficiently explored. Thus, using
      data from the Surveillance, Epidemiology, and End Results (SEER) Registry, this
      study aimed to compare the survival rates of patients with lymph node (LN)
      positive EC who received curative resection and were treated by neoadjuvant and
      adjuvant radiotherapy (RT), respectively. Methods: Retrospectively collected data
      from the SEER database using all 18 SEER registries on patients that underwent
      esophagectomy for EC was evaluated. All patients with LN positive pathology who
      received either neoadjuvant or adjuvant RT and curative intent esophagectomy from
      2004 to 2007 were included. A comparison of 5-year relative survival outcome
      among groups categorized by sex, race, age, histology, and tumor size was
      performed. Results: A total of 933 patients were evaluated; 636 (69%) and 297
      (31%) received RT in neoadjuvant and adjuvant setting respectively. Their overall
      5-year relative survival rates were 32.8% (95% CI: 28.7-36.9) and 26.5% (95% CI:
      21-32.3) (P=0.058). Patients in the neoadjuvant RT group who underwent curative
      resection for squamous cell carcinoma (SCC) of EC had an improved 5-year relative
      survival rate of 43.4% (95% CI: 32.5-53.8) compared to 26.5% (95% CI: 15.4-38.9)
      measured for the adjuvant RT group (P=0.03). The results further revealed a
      significant increase in the 5-year relative survival rates for stage T3 and Tx
      when RT was given in neoadjuvant setting compared to adjuvant RT group (T3 28.5%
      vs. 20.2%, P=0.011; Tx 46.3% vs. 8.9%, P=0.021). When the patients were grouped
      according to race, sex or age, or based on the timing of radiation relative to
      surgery, in the other histological or T stage groups, there were no statistically
      significant differences in the 5-year survival rates. Conclusions: Compared to
      adjuvant radiotherapy, neoadjuvant radiotherapy results in a better 5-year
      relative survival in patients with squamous cell neoplasms and/or T3, Tx stage
      disease.

PMID- 29184688
TI  - Age and factors associated with access and time to post-operative adjuvant
      chemotherapy in colon cancer: a French epidemiological study.
AB  - Background: Studies have shown the negative prognostic impact of increased time
      between colectomy and postoperative adjuvant chemotherapy (AC) in colon cancer
      (CC). Our aim was to investigate the role of age and non-organizational factors
      on access and time to AC. Methods: All adult patients undergoing surgery for
      stage II or III CC in the "Region Centre-Val de Loire" in 2013, were selected.
      Time to AC and socio-demographic factors were collected. Logistic regression
      modeling was used to identify factors associated with access to AC, and a
      multivariate analysis performed to identify factors associated with time to AC.
      Results: Among 404 stage II or III patients who underwent colectomy, 182 (45%;
      sex ratio 1.5; mean age 67.6 years; range 32-90) received AC. AC patients were
      younger than those without AC (67.6 vs. 77.9 years) and the difference was even
      greater for stage III patients (69.0 vs. 82.4). The median time to AC was 48
      days, exceeding 42 days in 60% of cases. Living alone, postoperative morbidities,
      and emergency colectomy were independently associated with increased time to AC.
      Age and other factors were not associated with delayed AC. Conclusions: Emergency
      colectomy, postoperative morbidities, and living alone are associated with
      increased time to AC. Organizational measures to reduce the time to AC are
      therefore unlikely to have an impact. In contrast, age is not associated with
      increased time to AC, but to access to AC. Reasons for omitting AC in older
      patients requires further study.

PMID- 29184689
TI  - Low-tie IMA and selective D3 lymph node sampling in laparoscopic rectal resection
      for carcinoma rectum: comparison of surgical and oncological outcomes with the
      open technique.
AB  - Background: Level of proximal lymphovascular ligation remains controversial in
      carcinoma rectum. High-tie inferior mesenteric artery (IMA) claims better lymph
      node clearance; low-tie IMA minimizes autonomic nerve injury (ANI) and ensures
      vascularity to anastomosis. Objective of this study is to compare postsurgical
      complications and oncological clearance in laparoscopic rectal resection (LRR)
      and open rectal resection (ORR) for carcinoma rectum, with low-tie IMA and
      selective D3 lymphadenectomy. Methods: Retrospective analysis was done comparing
      LRR and ORR done with low-tie IMA for carcinoma rectum/rectosigmoid for
      significant differences (P<0.05) regarding postsurgical complications and
      histopathology parameters. Results: A total of 118 patients; 48 in LRR group and
      70 in ORR group were studied. They were comparable in age, site of lesion and
      clinical TNM (cTNM) stage. Comorbidities and symptoms requiring upfront surgery
      were more among ORR. 75% LRR and 55.3% ORR had neoadjuvant chemoradiation
      (NACRT). Duration of surgery was longer in LRR. Clavien-Dindo grade >3 was
      similar in two groups. Histopathology characteristics were also comparable;
      including specimen length, lymph node yield, length of distal margin and
      pathologic TNM (pTNM) stage. Selective D3 lymphadenectomy was done in 37.5% LRR
      and 37.14% ORR. And 4.16% in LRR and 4.28% in ORR were had positive IMA root
      lymph nodes. Conclusions: The post-surgical complications and oncological
      clearance of LRR done with low-tie IMA and selective D3 lymphadenectomy were
      found equivalent to ORR. Low-tie IMA without routine splenic flexure mobilisation
      had no technical issues regarding the anastomosis.

PMID- 29184691
TI  - Long-term oncologic outcomes of stent as a bridge to surgery versus emergency
      surgery in malignant left side colonic obstructions: a meta-analysis.
AB  - Background: The placement of a metallic stent as a bridge to surgery (SBTS) could
      represents an option for the treatment of left-sided malignant colonic
      obstruction in centres with adequate skills. Several meta-analyses demonstrated
      better short-term outcomes after SBTS when compared with emergency surgery (ES);
      however, some studies reported a higher local recurrence rate. The aim of the
      present review is to investigate the long-term outcomes of stent bridge to
      surgery as compared to ES. Methods: A systematic review was performed to retrieve
      studies comparing long-term oncologic outcomes of SBTS and ES. Local and overall
      recurrence rate, overall and disease-free survival were retrieved and results
      were expressed as risk ratios. Results: Seventeen studies and a total of 1,333
      patients were included in the analysis. No significant differences were reported
      in recurrence rate [risk ratio (RR) =1.11; 95% confidence interval (95% CI): 0.84
      1.47, P=0.47], 3-year mortality (RR =0.90; 95% CI: 0.73-1.12, P=0.34) and 5-year
      mortality (RR =1.00; 95% CI: 0.82-1.22, P=0.99). There were no differences among
      randomized and observational studies. Conclusions: SBTS has similar long-term
      oncologic outcomes to ES and in centres with appropriate skill should be
      considered the best treatment option for left-sided malignant colonic
      obstructions.

PMID- 29184690
TI  - Correlation of tumor mutational burden and treatment outcomes in patients with
      colorectal cancer.
AB  - Background: The Cancer Genome Atlas (TCGA) showed that 16% of colorectal cancers
      (CRCs) display DNA repair mechanisms and high tumor mutational burden (TMB).
      Although, there is accumulating evidence of greater benefit of immunotherapy in
      tumors with high-TMB, its impact on response to chemotherapy is unknown. Methods:
      In this retrospective cohort study, we investigated the impact of TMB on
      progression-free survival (PFS) of CRC patients treated at tertiary care oncology
      clinics who had their tumors profiled by next-generation sequencing (NGS). Low
      TMB (TMB-L) and intermediate/high TMB (TMB-I/H) were defined as <=5 mutations per
      base (MB) or >=6 MB, respectively. Results: Seventy-four CRC patients (61 colon
      and 13 rectal cancers) were identified from the database. In the TMB-L cohort,
      irinotecan-based chemotherapy treated patients had improved PFS compared to
      oxaliplatin-based chemotherapy treated patients (11.9 vs. 6.5 months, P<0.001).
      No difference in PFS was observed between the two treatment cohorts in TMB-I/H
      group. There was also no difference in time to recurrence in the TMB-L and TMB
      I/H arms in patients treated with oxaliplatin-based therapy in perioperative
      setting. Conclusions: TMB-L may be a predictive biomarker in a subset of CRC
      patients treated with chemotherapy but these results need to confirmed in larger
      studies.

PMID- 29184692
TI  - Advanced duodenal neoplasia and carcinoma in familial adenomatous polyposis:
      outcomes of surgical management.
AB  - Background: In addition to the presence of neoplasia in the colon and rectum,
      patients with familial adenomatous polyposis (FAP) may develop numerous polyps
      and carcinoma within the upper gastrointestinal tract. Methods: The aim of the
      present paper was to review the incidence advanced duodenal polyposis or cancer
      and their surgical outcomes. A retrospective review of patients' records from our
      department was performed. Information was retrieved from a prospective collected
      data, including clinical (gender, age, family history), endoscopic [association
      with colorectal cancer (CRC), polyposis severity, age at diagnosis] and surgical
      management (age, time from the index surgery, type of procedure, morbidity).
      Duodenal adenomatosis at the time of surgery was classified according to
      Spigelman stages. Results: In a group of 145 FAP patients, 8 (5.5%) had been
      surgically treated for duodenal advanced neoplasia [3] or cancer [5]. There were
      included 2 women and 6 men whose first endoscopic examination and diagnosis of
      advanced neoplasia/cancer was made at median ages of 47.3 [28-63] and 51.8 years,
      respectively. Duodenal carcinomas occurred later (55.8 years) when compared to
      advanced adenomatosis (45.3 years). Three patients were diagnosed due to
      symptoms, while the others were detected under endoscopic surveillance. Age
      interval between FAP treatment and duodenal neoplasia diagnosis was 15.3 years [0
      47]. All but one patient underwent duodenopancreatectomy (DP). Two from the 7
      patients undergoing DP died, one from pulmonary embolism 30 days after surgery
      and the other from recurrent T4N0 duodenal tumor. Thus, major operative morbidity
      and mortality were 12.5%. Conclusions: In this single-center Brazilian series of
      FAP patients: (I) advanced duodenal neoplasia or cancer requiring surgery
      occurred in 5.5% of patients; (II) when reaching the fifth decade of life,
      patients should be carefully evaluated to diagnose and treat early lesions; (III)
      in spite of the technical complexity of DP, operative morbidity is acceptable in
      experienced hands; and (IV) continuous surveillance is necessary during follow
      up.

PMID- 29184693
TI  - Predictors of intermediate-term survival with destination locoregional therapy of
      hepatocellular cancer in patients either ineligible or unwilling for liver
      transplantation.
AB  - Intra-arterial or percutaneous locoregional therapies (LRT) are often employed to
      maintain potential liver transplant (LT) recipients with hepatocellular carcinoma
      (HCC) within T2/Milan criteria. Predictors of survival when LRT is used as
      destination therapy in those who are either ineligible or unwilling for LT remain
      poorly defined. We evaluated predictors of 3-year survival with destination LRT
      in a population of cirrhotic patients diagnosed with HCC, presenting within T2
      criteria, and either ineligible or unwilling for LT. The cohort surviving 3 years
      had a significantly lower model for end-stage liver disease (MELD) score at HCC
      diagnosis (9.7 vs. 11.4, P=0.037) and MELD following initial locoregional therapy
      (10.7 vs. 13.3, P=0.008) compared to those not surviving three years despite
      similar demographic, tumor, and treatment variables. LRT as destination therapy
      results in modest intermediate term survival, with liver function at presentation
      and immediately following initiation of LRT predicting intermediate survival with
      this approach.

PMID- 29184694
TI  - Survivorship after treatment of pancreatic cancer: insights via an Internet-based
      survivorship care plan tool.
AB  - Pancreatic cancer survivors face a unique set of challenges in survivorship, yet
      structured survivorship care planning is lacking in practice. Survivorship care
      plans (SCPs) are an essential part of quality cancer care and can facilitate the
      transition following active treatment; the use of SCPs in pancreatic cancer
      survivors, however, has not been explored. With a convenience sample of 117
      pancreatic cancer survivors and proxies who used an Internet-based SCP tool, we
      examined treatment details, patient-reported outcomes, and survivorship
      practices. Thirty-one percent of survivors were 2 years or greater from diagnosis
      with a median current age of 62 years. Most patients had received multimodality
      therapy (67%): 68%, 86%, and 43% reported surgical intervention, intravenous
      chemotherapy, and radiation therapy for their pancreatic cancer, respectively.
      Survivors commonly reported fatigue, cognitive change, neuropathy, pancreatic
      insufficiency, and chronic radiation dermatitis related to treatment. Most
      survivors are managed (47%) or co-managed (35%) by an oncology specialist;
      however, this percentage decreases over time with consequent increase in
      management by primary care providers alone. Only 5% had previously been offered
      an SCP. Of the 24 users who responded to a follow-up satisfaction survey, 83%
      indicated they would share the SCP with their healthcare team although half of
      respondents felt it should include more information. In all, our results
      demonstrate that there is a population of pancreatic cancer survivors who exist
      and seek survivorship support although structured survivorship care planning is
      lacking in practice. SCPs have a potentially valuable role for these survivors
      via communication of treatment-related effects and coordination across
      multidisciplinary healthcare teams. Further development and evaluation of SCPs is
      needed for this underserved survivor population.

PMID- 29184695
TI  - Demographic and clinical factors associated with suicide in gastric cancer in the
      United States.
AB  - While increased suicidal tendencies among cancer patients have been well
      documented, there has been no specific examination of suicide and gastric cancer.
      The purpose of this study is to characterize suicide incidence among patients
      diagnosed with gastric cancer from 1973 to 2013 and identify variables associated
      with higher suicide rates. Patients with gastric cancer were identified in the
      Surveillance, Epidemiology, and End Results (SEER) database of the National
      Cancer Institute. The study included clinical and demographic data from 1973 to
      2013. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs)
      were calculated. Comparisons with the general US population were based on
      mortality data collected by the Centers for Disease Control and Prevention's
      National Center for Injury Prevention and Control using the Web-based Injury
      Statistics Query and Reporting System. Multivariable logistic regression models
      generated odds ratios (ORs) to assess factors associated with increased suicide
      in gastric malignancy. There were 210 suicides for patients with gastric cancer
      (SMR, 3.21; 95% CI: 2.80-3.67). Female gender (SMR 8.54), White race (SMR 4.08),
      age <=39 years (SMR 3.06), and age 70-79 years (SMR 2.90), were found to be
      significant for an increased incidence of suicide compared with the general
      population. There was not a statistically significant relationship between
      suicide and marital status, income, mode of radiation therapy, and the role of
      surgical intervention. Approximately 77% of deaths by suicide occurred within the
      first year following diagnosis. Female gender, White race, age <=39 years, and
      age 70-79 years are factors associated with increased risk of suicide in patients
      with gastric cancer. These results, coupled with further studies and analyses,
      will be used to formulate a comprehensive suicide risk factor scoring system for
      screening all cancer patients.

PMID- 29184696
TI  - Adaptive radiation dose escalation in rectal adenocarcinoma: a review.
AB  - Total mesorectal excision (TME) after neoadjuvant chemoradiotherapy (CRT) has
      offered superior control for patients with locally advanced rectal cancer, but
      can carry a quality of life cost. Fortunately, some patients achieve a complete
      response after CRT alone without the added morbidity caused by surgery. Efforts
      to increase fidelity of radiation treatment planning and delivery may allow for
      escalated doses of radiotherapy (RT) with limited off-target toxicity and elicit
      more pathological complete responses (pCR) to CRT thereby sparing more rectal
      cancer patients from surgery. In this review, methods of delivering escalated RT
      boost above 45-50.4 Gy are discussed including: 3D conformal, intensity-modulated
      radiotherapy (IMRT), and brachytherapy. Newly developed adaptive boost strategies
      and imaging modalities used in RT planning and response evaluation such as
      magnetic resonance imaging (MRI) and positron emission tomography (PET) are also
      discussed.

PMID- 29184697
TI  - Clinical presentation, diagnosis, classification and management of peritoneal
      mesothelioma: a review.
AB  - Peritoneal mesothelioma (PM) is an uncommon but a serious, and often, fatal
      primary peritoneal tumour, with increasing incidence worldwide. Conventional
      systemic chemotherapy, generally based on experience with pleural mesothelioma,
      usually has disappointing results considering PM as a terminal condition.
      Patients usually present with non-specific symptoms of abdominal distension and
      pain making the diagnosis challenging. As PM is confined to the abdomen for all,
      or much, of its clinical course, a multimodality treatment combining
      cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy
      (HIPEC) has emerged as a new standard of care, and has been reported to achieve
      promising survival outcomes and local disease control in selected patients with
      PM. This review updates the presentation, diagnosis, classification and treatment
      strategies for PM.

PMID- 29184699
TI  - Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related
      to Lynch syndrome.
AB  - Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary
      syndromes. An association between Lynch syndrome (LS) and P-NETs has been
      suggested, however it has not been confirmed to date. We describe the first case
      associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20
      years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC),
      infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non
      functioning P-NETs and sebomatricoma. With the exception of one P-NET, all these
      conditions were associated with LS, as confirmed by immunohistochemistry (IHC)
      and polymerase chain reaction (PCR). LS is caused by a mutation of a mismatch
      repair (MMR) gene which leads to a loss of expression of its protein. CRC is the
      most common tumor, followed by EC. Pancreatic tumors have also been associated
      with LS. Diagnosis of LS is based on clinical criteria (Amsterdam II and
      Bethesda) and genetic study (MMR gene mutation). The association between LS and
      our patient's tumors was confirmed by IHC (loss of expression of proteins MLH1
      and its dimer PMS2) and the detection of microsatellite instability (MSI) using
      PCR.

PMID- 29184698
TI  - Case report: primary acinar cell carcinoma of the liver treated with
      multimodality therapy.
AB  - We describe a case of primary acinar cell carcinoma (ACC) originating in the
      liver in a 54-year-old female, diagnosed following persistent abnormal elevated
      liver function. Imaging revealed two masses, one dominant lesion in the right
      hepatic lobe and another in segment IVA. A right hepatectomy was performed to
      remove the larger lesion, while the mass in segment IVA was unresectable due to
      its proximity to the left hepatic vein. Immunohistochemical staining showed
      positivity for trypsin and chymotrypsin. Postoperatively the patient underwent
      hepatic arterial embolization of the other unresectable lesion followed by FOLFOX
      chemotherapy. At 20 months from diagnosis the patient is currently under
      observation with a decreasing necrotic mass and no other disease evident. Based
      on histology, immunohistochemistry and radiological findings a diagnosis of
      primary ACC of the liver was made. Genomic assessment of somatic mutations within
      the patient's tumor was also performed through next generation sequencing and
      findings were consistent with an acinar malignancy. This case highlights a rare
      tumor subtype treated with a combination of therapeutic modalities through a
      multidisciplinary approach.

PMID- 29184700
TI  - The burden of congenital rubella syndrome in the Philippines: results from a
      retrospective assessment.
AB  - Introduction: In line with the regional aim of eliminating rubella and congenital
      rubella syndrome (CRS), phased introduction of rubella-containing vaccines (RCV)
      in the Philippines' routine immunization programme began in 2010. We estimated
      the burden of CRS in the country before widespread nationwide programmatic RCV
      use. Methods: We performed a retrospective chart review in four tertiary
      hospitals. Children born between 1 January 2009 and 31 December 2014 and
      identified as possible CRS cases based on the presence of one or more potential
      manifestations of CRS documented in hospital or clinic charts were reviewed.
      Cases that met the clinical case definition of CRS were classified as either
      confirmed (with laboratory confirmation) or probable (without laboratory
      confirmation). Cases that did not fulfil the criteria for either confirmed or
      probable CRS were excluded from the analysis. Results: We identified 18 confirmed
      and 201 probable cases in this review. Depending on the hospital, the estimated
      incidence of CRS ranged from 30 to 233 cases per 100 000 live births. The
      estimated national burden of CRS was 20 to 31 cases per 100 000 annually.
      Discussion: This is the first attempt to assess the national CRS burden using in
      country hospital data in the Philippines. Prospective surveillance for CRS and
      further strengthening of the ongoing measles-rubella surveillance are necessary
      to establish accurate estimates of the burden of CRS and the impact of
      programmatic RCV use in the future.

PMID- 29184701
TI  - Paneth cells in intestinal physiology and pathophysiology.
AB  - Small intestinal mucosa is characterised by villus forming connective tissues
      with highly specialised surface lining epithelial cells essentially contributing
      to the establishment of the intestinal border. In order to perform these diverse
      functions, spatially distinct compartments of epithelial differentiation are
      found along the crypt-villus axis, including Paneth cells as a highly specialised
      cell type. Paneth cells locate in crypts and assist undifferentiated columnar
      cells, called crypt base columnar cells, and rapidly amplifying cells in the
      regeneration of absorptive and secretory cell types. There is some evidence that
      Paneth cells are involved in the configuration and function of the stem cell zone
      as well as intestinal morphogenesis and crypt fission. However, the flow of
      Paneth cells to crypt bottoms requires strong Wnt signalling guided by EphB3 and
      partially antagonised by Notch. In addition, mature Paneth cells are essential
      for the production and secretion of antimicrobial peptides including alpha
      defensins/cryptdins. These antimicrobials are physiologically involved in shaping
      the composition of the microbiome. The autophagy related 16-like 1 (ATG16L1) is a
      genetic risk factor and is involved in the exocytosis pathway of Paneth cells as
      well as a linker molecule to PPAR signalling and lipid metabolism. There is
      evidence that injuries of Paneth cells are involved in the etiopathogenesis of
      different intestinal diseases. The review provides an overview of the key points
      of Paneth cell activities in intestinal physiology and pathophysiology.

PMID- 29184702
TI  - Pharmacological inhibition of diacylglycerol acyltransferase-1 and insights into
      postprandial gut peptide secretion.
AB  - AIM: To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1
      (DGAT1) plays in postprandial gut peptide secretion and signaling. METHODS: The
      standard experimental paradigm utilized to evaluate the incretin response was a
      lipid challenge. Following a lipid challenge, plasma was collected via cardiac
      puncture at each time point from a cohort of 5-8 mice per group from baseline at
      time zero to 10 h. Incretin hormones [glucagon like peptide-1 (GLP-1), peptide
      tyrosine-tyrosine (PYY) and glucose dependent insulinotropic polypeptide (GIP)]
      were then quantitated. The impact of pharmacological inhibition of DGAT1 on the
      incretin effect was evaluated in WT mice. Additionally, a comparison of loss of
      DGAT1 function either by genetic ablation or pharmacological inhibition. To
      further elucidate the pathways and mechanisms involved in the incretin response
      to DGAT1 inhibition, other interventions [inhibitors of dipeptidyl peptidase-IV
      (sitagliptin), pancreatic lipase (Orlistat), GPR119 knockout mice] were
      evaluated. RESULTS: DGAT1 deficient mice and wildtype C57/BL6J mice were lipid
      challenged and levels of both active and total GLP-1 in the plasma were
      increased. This response was further augmented with DGAT1 inhibitor PF-04620110
      treated wildtype mice. Furthermore, PF-04620110 was able to dose responsively
      increase GLP-1 and PYY, but blunt GIP at all doses of PF-04620110 during lipid
      challenge. Combination treatment of PF-04620110 and Sitagliptin in wildtype mice
      during a lipid challenge synergistically enhanced postprandial levels of active
      GLP-1. In contrast, in a combination study with Orlistat, the ability of PF
      04620110 to elicit an enhanced incretin response was abrogated. To further
      explore this observation, GPR119 knockout mice were evaluated. In response to a
      lipid challenge, GPR119 knockout mice exhibited no increase in active or total
      GLP-1 and PYY. However, PF-04620110 was able to increase total GLP-1 and PYY in
      GPR119 knockout mice as compared to vehicle treated wildtype mice. CONCLUSION:
      Collectively, these data provide some insight into the mechanism by which
      inhibition of DGAT1 enhances intestinal hormone release.

PMID- 29184703
TI  - Effects of commercially produced almond by-products on chemotherapy-induced
      mucositis in rats.
AB  - AIM: To determine if almond extracts reduce the severity of chemotherapy-induced
      mucositis as determined through biochemical, histological and behavioural
      markers. METHODS: Intestinal mucositis is a debilitating condition characterized
      by inflammation and ulceration of the gastrointestinal mucosa experienced by
      cancer patients undergoing chemotherapy. Certain bioactive plant products have
      shown promise in accelerating mucosal repair and alleviating clinical symptoms.
      This study evaluated almond extracts for their potential to reduce the severity
      of chemotherapy-induced mucositis in Dark Agouti rats. Female Dark Agouti rats
      were gavaged (days 3-11) with either PBS, almond hull or almond blanched water
      extract at two doses, and were injected intraperitoneally with 5-fluorouracil (5
      FU-150 mg/kg) or saline on day 9 to induce mucositis. Burrowing behavior,
      histological parameters and myeloperoxidase activity were assessed. RESULTS:
      Bodyweight was significantly reduced in rats that received 5-FU compared to
      saline-treated controls (P < 0.05). Rats administered 5-FU significantly
      increased jejunal and ileal MPO levels (1048%; P < 0.001 and 409%; P < 0.001),
      compared to healthy controls. Almond hull extract caused a pro-inflammatory
      response in rats with mucositis as evidenced by increased myeloperoxidase
      activity in the jejunum when compared to 5-FU alone (rise 50%, 1088 +/- 96 U/g vs
      723 +/- 135 U/g, P = 0.02). Other extract-related effects on inflammatory
      activity were minimal. 5-FU significantly increased histological severity score
      compared to healthy controls confirming the presence of mucositis (median of 9.75
      vs 0; P < 0.001). The extracts had no ameliorating effect on histological
      severity score in the jejunum or ileum. Burrowing behavior was significantly
      reduced in all chemotherapy-treated groups (P = 0.001). The extracts failed to
      normalize burrowing activity to baseline levels. CONCLUSION: Almond extracts at
      these dosages offer little beneficial effect on mucositis severity. Burrowing
      provides a novel measure of affective state in studies of chemotherapy-induced
      mucositis.

PMID- 29184704
TI  - Surgical nuances of circumferential lumbar spondylectomy: A case report and short
      literature review.
AB  - Background: Chordomas are uncommon malignant bone tumors that are often minimally
      symptomatic for several years. By the time they are diagnosed, these lesions are
      typically large, involve major neural, bony, and vascular structures, and are no
      longer readily resectable. This leads to a high recurrence rate. Case
      Description: In this case report, we present a 67-year-old male with
      nonmechanical axial back pain, neurogenic claudication, and a large mass centered
      at the L3 level on magnetic resonance imaging consistent with a locally invasive
      chordoma. The patient underwent surgical resection that required a complete
      lumbar spondylectomy utilizing a three-stage approach, leading to incomplete
      tumor excision. The patient's residual postoperative symptoms included
      paresthesias/numbness in the right anterior thigh and a partial (4/5) right-sided
      foot drop. At the time of discharge, there were plans for future proton beam
      therapy. Conclusions: Because of their relative resistance to chemotherapeutic
      agents, the optimal surgical management of chordomas is gross total en-bloc
      excision. Unfortunately, this is rarely feasible.

PMID- 29184705
TI  - Phrenic nerve decompression for the management of unilateral diaphragmatic
      paralysis - preoperative evaluation and operative technique.
AB  - Background: Unilateral diaphragmatic paralysis (UDP) can be a very disabling,
      typically causing shortness of breath and reduced exercise tolerance. We present
      a case of a surgical decompression of the phrenic nerve of a patient who
      presented with UDP, which occurred following cervical spine surgery. Methods: The
      workup for the etiology of UDP demonstrated paradoxical movement on "sniff test"
      and notably impaired pulmonary function tests. Seven months following the onset
      of the UDP, he underwent a surgical decompression of the phrenic nerve at the
      level of the anterior scalene. Results: He noted rapid symptomatic improvement
      following surgery and reversal of the above noted objective findings was
      documented. At his 4-year follow-up, he had complete resolution of his clinical
      symptoms. Repeated physiologic testing of his respiratory function had shown a
      complete reversal of his UDP. Conclusions: Anatomical compression of the phrenic
      nerve by redundant neck vasculature should be considered in the differential
      diagnosis of UDP. Here we demonstrated the techniques in workup and surgical
      management, with both subjective and objective evidence of success.

PMID- 29184706
TI  - Cervical intramedullary spinal cord lipoma.
AB  - Background: Intramedullary, nondysraphic, spinal cord lipomas are rare and
      account for less than 1% of all spinal cord lesions. Symptoms typically consist
      of a progressive myelopathy associated with increasing degrees of paralysis
      (e.g., quadriparesis/plegia, paraparesis/plegia). Case Description: A 39-year-old
      male, without a history of spinal dysraphism, presented with a progressive
      spastic quadriparesis. This was attributed to magnetic resonance-documented large
      intramedullary cervical lipoma. Following partial intramedullary surgical
      debulking of the lesion, the patient neurologically improved. Conclusion: Partial
      debulking of a cervical intramedullary lipoma in a patient who originally
      presented with a severe quadriparesis resulted in significant neurological
      improvement. Notably, utilization of intraoperative ultrasonography, CO2 laser,
      and both motor evoked and somatosensory evoked potentials can be helpful during
      the removal of such lipomas.

PMID- 29184707
TI  - Hydrocephalus as a rare compilation of vertebrobasilar dolichoectasia: A case
      report and review of the literature.
AB  - Background: Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized
      by significant expansion, elongation, and tortuosity of the vertebrobasilar
      arteries. Hydrocephalus is a rare compilation of VBD. Case Description: In this
      study, we report a 68-year-old male presenting with headache, progressive
      decreased visual acuity, memory loss, imbalance while walking, and episodes of
      urinary incontinency. The patient was diagnosed with dolichoectasia of basilar
      artery causing compression of the third ventricular outflow and thus, presenting
      with hydrocephalus documented with brain computed tomography scan and brain
      magnetic resonance imaging. The patient underwent surgical operation and
      ventriculoperitoneal shunt placement. Conclusion: In the case of hydrocephalus or
      normal pressure hydrocephalous, VBD should be considered as a differential
      diagnosis.

PMID- 29184708
TI  - Solitary Aggregatibacter aphrophilus tectal abscess in an immunocompetent
      patient.
AB  - Background: A solitary abscess involving the tectum, specifically by
      Aggregatibacter aphrophilus, is an extremely rare condition with no known
      reported cases to date. Case Description: Here, we present a case of isolated
      solitary midbrain tectum abscess in an immunocompetent 28-year-old male who was
      empirically diagnosed as a primary tectal tumor at an outside hospital where he
      also underwent placement of a ventriculoperitoneal shunt (VPS) for obstructive
      hydrocephalus. Eight weeks later he was readmitted with a VPS infection. He was
      transferred to our institution where the VPS was removed and he was started on
      broad-spectrum antibiotics. Cerebrospinal fluid (CSF) culture revealed A.
      aphrophilus. All other workup was negative for infectious etiologies. The tectal
      lesion completely resolved after 15 weeks of intravenous ceftriaxone without
      surgical aspiration. Conclusion: We suggest that an empiric diagnosis of tectal
      glioma should be made with caution for a ring-enhancing mass. CSF should be
      routinely cultured at the time of operative diversion if abscess is a
      possibility.

PMID- 29184709
TI  - Gamma knife radiosurgery for cerebellopontine angle epidermoid tumors.
AB  - Background: Intracranial epidermoid tumors are commonly found in the
      cerebellopontine angle where they usually present with either trigeminal
      neuralgia or hemifacial spasm. Radiosurgery for these tumors has rarely been
      reported. The purpose of this study is to assess the safety and clinical outcome
      of the treatment of cerebellopontine epidermoid tumors with gamma knife
      radiosurgery. Methods: This is a retrospective study involving 12 patients
      harboring cerebellopontine angle epidermoid tumors who underwent 15 sessions of
      gamma knife radiosurgery. Trigeminal pain was present in 8 patients and
      hemifacial spasm in 3 patients. All cases with trigeminal pain were receiving
      medication and still uncontrolled. One patient with hemifacial spasm was
      medically controlled before gamma knife and the other two were not. Two patients
      had undergone surgical resection prior to gamma knife treatment. The median
      prescription dose was 11 Gy (10-11 Gy). The tumor volumes ranged from 3.7 to 23.9
      cc (median 10.5 cc). Results: The median radiological follow up was 2 years (1-5
      years). All tumors were controlled and one tumor shrank. The median clinical
      follow-up was 5 years. The trigeminal pain improved or disappeared in 5 patients,
      and of these, 4 cases stopped their medication and one decreased it. The
      hemifacial spasm resolved in 2 patients who were able to stop their medication.
      Facial palsy developed in 1 patient and improved with conservative treatment.
      Transient diplopia was also reported in 2 cases. Conclusion: Gamma knife
      radiosurgery provides good clinical control for cerebellopontine angle epidermoid
      tumors.

PMID- 29184711
TI  - Adult sacrococcygeal teratoma with coccygectomy: A case report with a review of
      the literature.
AB  - Background: Saccrococcygeal teratomas (SCT) are derived from embryonic germ cell
      layers. They frequently present at the base of the coccyx within the pelvis.
      While these tumors are common in children, they are exceedingly rare in adults.
      In adults, a majority of these tumors are intrapelvic and associated with a low
      risk of malignant transformation. Therefore, this contributes to a good prognosis
      following resection of mostly benign lesions. Case Description: An adult female
      with chronic pelvic pain presented with a sacral teratoma. She failed
      conservative treatment and underwent a coccygectomy with an en-bloc excision of
      the tumor. Microscopic histological analysis showed no evidence of immature or
      malignant elements, confirming the diagnosis of a mature, benign, cystic SCT.
      Conclusions: Mature SCTs in adults are rare malignant lesions. In this case, the
      patient was cured following primary surgical excision requiring en-bloc
      coccygectomy.

PMID- 29184710
TI  - Retrospective study of 229 surgically treated patients with brain metastases:
      Prognostic factors, outcome and comparison of recursive partitioning analysis and
      diagnosis-specific graded prognostic assessment.
AB  - Background: Metastases are the most frequent tumors in the brain. Most often used
      scoring systems to predict the outcome are the RPA (Recursive Partitioning
      Analysis) classification and the DS-GPA (Diagnosis-Specific Graded Prognostic
      Assessment) score. The goal of our study was to determine prognostic factors
      which influence outcome in patients who undergo surgery for brain metastases and
      to compare different outcome scores. Methods: Two hundred and twenty-nine
      patients who underwent surgery for brain metastases in our institution between
      January 2005 and December 2014 were included in the study. Patient data were
      evaluated retrospectively. Results: The mean survival time was 19.2 months
      (median survival time, MST: 8 months), for patients with a single metastasis (n =
      149) 17.6 months (MST: 8 months), and for patients with multiple metastases (n =
      80) 17.9 months (MST: 6 months). Significant influence on MST had age <65 years
      (9 vs. 5 months, P = 0.002), female sex (10 vs. 6 months, P < 0.001), RPA Class I
      and II (11 vs. 4 months, P < 0.001), Karnofsky score >70% (11 vs. 4 months, P <
      0.001), and postoperative radiotherapy (8 vs. 5 months, P < 0.002). To evaluate
      the diagnostic power of DS-GPA and RPA score in respect of survival, two Cox
      regressions were modeled, where the RPA classification showed a better predictive
      power. Conclusion: Favorable factors for prolonged survival were KPS >70%, RPA
      Class I and II, age <65 years, female sex, a DS-GPA Score of 2.5-3 and 3.5-4, and
      adjuvant radiotherapy. The RPA Classification was more accurate in predicting the
      outcome than the DS-GPA score.

PMID- 29184712
TI  - Asymmetric neuromodulation of motor circuits in Parkinson's disease: The role of
      subthalamic deep brain stimulation.
AB  - Whereas hemispheric dominance is well-established for appendicular motor control
      in humans, the evidence for dominance in axial motor control is still scarce. In
      Parkinson's disease (PD), unilateral (UL) onset of appendicular motor symptoms
      corresponds with asymmetric neurodegeneration predominantly affecting
      contralateral nigrostriatal circuits. Disease progression yields bilateral and
      axial motor symptoms but the initial appendicular asymmetry usually persists.
      Furthermore, there is evidence for hemispheric dominance for axial motor
      dysfunction in some of these patients. Dopaminergic medications improve
      appendicular symptoms but can also produce motor complications over time. Once
      these complications develop, bilateral (BL) deep brain stimulation (DBS) of the
      subthalamic nuclei (STN) can significantly improve appendicular symptoms while
      reducing medication doses and motor complications. Conversely, axial motor
      symptoms remain a significant source of disability, morbidity, and mortality for
      patients with PD. These axial symptoms do not necessarily improve with
      dopaminergic therapy, might not respond, and could even worsen after BL-DBS. In
      contrast to medications, DBS provides the opportunity to modify stimulation
      parameters for each cerebral hemisphere. Identical, BL-DBS of motor circuits with
      hemispheric dominance in PD might produce overstimulation on one side and/or
      understimulation on the other side, which could contribute to motor dysfunction.
      Several studies based on asymmetry of appendicular motor symptoms already support
      an initial UL rather than BL approach to DBS in some patients. The response of
      axial motor symptoms to UL versus BL-DBS remains unclear. Nonetheless, UL-DBS,
      staged BL-DBS, or asymmetric programming of BL-DBS could also be considered in
      patients with PD.

PMID- 29184714
TI  - Clinical significance of thickened sphenoid sinus mucosa in Rathke's cleft cyst.
AB  - Background: To determine the clinical significance of thickening of the sphenoid
      sinus mucosa (TSSM) in Rathke's cleft cyst (RCC). Methods: We retrospectively
      reviewed patients with pituitary lesions. A total of 99 patients, who underwent
      surgery of pituitary lesions between 2008 and 2015, were analyzed to evaluate the
      clinical significance of TSSM using magnetic resonance imaging. The patients with
      TSSM were evaluated for their characteristics. Results: Of the 99 operations, 15
      patients with paranasal sinusitis, direct invasion to the sellar floor, and/or a
      history of transsphenoidal surgery were excluded. There were 51 pituitary
      adenomas (PAs), 18 RCCs, and 15 other tumors. TSSM was observed in 6 patients
      (7.1%). Pathologies included 3 RCCs (16.7%), 1 PA (2.0%), and 2 other lesions.
      Three RCCs were especially analyzed. The pituitary dysfunction was found in all 3
      patients with TSSM, whereas that was noted in 2 of 15 patients (13.3%) without
      TSSM. The sensitivity was 60%, specificity was 86.7%, and the positive predictive
      value was 100%. There was no significant difference in the age, thickness of
      TSSM, symptoms, and squamous metaplasia between patients with and without TSSM.
      Conclusions: TSSM occurs more frequently in RCCs than in PAs. TSSM can
      potentially suggest hypopituitarism in RCCs. The surgical and/or endocrinological
      interventions are required for preventing further endocrine deterioration.

PMID- 29184713
TI  - Posterior atlantoaxial fusion using a C2 transverse foramen-penetrating screw: A
      technical note.
AB  - Background: Although recent development of screw instrumentation techniques for
      rigid fixation of the atlantoaxial joint has increased surgical options, patients
      in whom screws of any type cannot be safely placed are sometimes encountered. We
      present a unique surgical technique for C1-2 transarticular screw placement
      utilizing a novel trajectory. Methods: A 35-year-old male with a history of
      Down's syndrome and cognitive dysfunction with hyperkinesis spontaneously
      developed rapid onset of tetraparesis and gait disturbance. Radiographs of the
      cervical spine revealed atlantoaxial subluxation (AAS) that could not be reduced.
      Computed tomography (CT) of the head showed multiple subacute cerebral
      infarctions in the territory of the right vertebral artery (VA). Three
      dimensional CT angiography of the craniovertebral junction additionally confirmed
      right VA occlusion at the C2/3 level, a left C2 origin of the posterior inferior
      cerebellar artery, and hypoplasia of the bilateral C2 pedicles/C2 lamina. Because
      traditional screw-placement was not feasible, we performed a unique atlantoaxial
      fusion utilizing a C2 transverse foramen-penetrating screw with iliac bone
      grafting performed under neuronavigation. Results: The postoperative course was
      uneventful, and the patient regained the ability to ambulate, returning to his
      previous level of function. The CT of the cervical spine 12 months
      postoperatively showed rigid bony C1-C2 fusion, without recurrence of stroke.
      Conclusion: We introduced a novel C1-C2 transarticular screw-placement technique
      in which the trajectory went through the ipsilateral VA foramen due to already
      extent VA occlusion.

PMID- 29184715
TI  - Unusual case of hemangioblastoma of the cerebellopontine angle.
AB  - Background: Hemangioblastomas are the most common primary tumor of the posterior
      fossa. There are few cases of hemangioblastoma of the cerebellopontine angle
      (CPA). When present in this location, hemangioblastoma presents a diagnostic
      challenge as its imaging findings closely resemble those of vestibular schwannoma
      (VS), which is much more common in the CPA. Case Description: We report the case
      of a 42-year-old man presenting with vertigo and diplopia found to have a CPA
      tumor with imaging resembling VS. He underwent retrosigmoidal resection of his
      tumor, which was found to be a hemangioblastoma. Conclusion: Hemangioblastoma,
      though rare in the CPA, should be considered in the differential diagnosis of CPA
      tumors.

PMID- 29184716
TI  - Refractory intracranial hypertension in traumatic brain injury: Proposal for a
      novel score to assess the safety of lumbar cerebrospinal fluid drainage.
AB  - Background: Cerebrospinal fluid (CSF) drainage via ventricular puncture is an
      established therapy of elevated intracranial pressure (ICP). In contrast, lumbar
      CSF removal is believed to be contraindicated with intracranial hypertension.
      Methods: We investigated the safety and efficacy of lumbar CSF drainage to
      decrease refractory elevated ICP in a small cohort of patients with traumatic
      brain injury (TBI). A score (0-8 points) was used to assess computed tomography
      (CT) images for signs of herniation and for patency of the basal cisterns. All
      patients received lumbar CSF drainage either as a continuous drainage or as a
      single lumbar puncture (LP). Type and method of CSF drainage, mean ICP 24 h prior
      and after CSF removal, and adverse events were documented. Outcome was assessed
      after 3 months (with dichotomized Glasgow outcome scale). Results: Eight patients
      were evaluated retrospectively. n = 5 suffered a moderate, n = 2 a severe TBI
      (one Glasgow coma score not documented). The CT score was >=5 in all patients
      prior to LP and decreased after puncture without clinical consequences in two
      patients. The amount of CSF removal did not correlate with score changes (P =
      0.45). CSF drainage led to a significant reduction of mean ICP (from 22.3 to 13.9
      mmHg, P = 0.002). Continuous drainage was more effective than a single LP. Three
      of eight patients reached a favorable outcome. Conclusions: Lumbar CSF removal
      for the treatment of intracranial hypertension is effective and safe, provided
      the basal cisterns are discernible, equivalent to >=5 points in the proposed new
      score. The score needs further validation.

PMID- 29184717
TI  - Intraventricular hemorrhage possibly extending from an infratentorial subdural
      hematoma via a perforated suprapineal recessus in a full-term neonate.
AB  - Background: Although intraventricular hemorrhage (IVH) is very rarely reported in
      full-term neonates, it may occur in children with perinatal trauma, asphyxia, and
      coagulation disorders, and may originate in the choroid plexus and residual
      subependymal germinal matrix layer. Case Description: We present the case of a
      full-term baby with IVH. She had no perinatal problems or coagulation disorders.
      Sagittal views of neuroimages demonstrated that the IVH possibly extended from a
      subdural hemorrhage (SDH) in the infratentorial area via a perforated suprapineal
      recessus. This was barely visible on a conventional axial view of a computed
      tomographic scan. Conclusion: When the etiopathogenesis of IVH in a full-term
      baby with an uncomplicated delivery cannot be clearly defined, multi-directional
      and multi-modal neuroimaging may be useful.

PMID- 29184718
TI  - Three consecutive neurotomies in one patient for the treatment of spastic
      hemiplegia: Spinal, median, and foot toes common flexor.
AB  - Background: Neurotomies were one of the first procedures performed in the field
      of functional neurosurgery. Microstimulators and microscopes facilitate the
      performance of neurotomies to treat focal spasticity. This report shows how three
      different consecutive neurotomies were performed in one patient with chronic left
      upper/lower extremity spasticity. Case Description: A 65-year-old male with
      intractable epilepsy underwent a right temporal lobectomy for seizure control.
      Postoperatively, he developed left upper/lower extremity spasticity attributed to
      a postoperative right internal capsule infarct. The severe spasticity persisted
      despite the administration of conventional drugs, rehabilitation efforts, and
      botulinic toxin injections. Three sequential selective neurotomies (e.g., spinal,
      median, and foot common flexor nerves) were next performed. Postoperatively, the
      neurotomies resulted in significant symptomatic long-term improvement, 6 years
      after spinal neurotomy, 7 years after median neurotomy, and 9 years after common
      flexor neurotomy. Spasticity scores diminished from 4 to 0 points on the Ashworth
      scale and from 4 to 0 points on the Held-Tardieu scale for each muscular region.
      Conclusion: Multiple regional neurotomies were effective in the management of
      left-sided postoperative spasticity in a patient who underwent a temporal
      lobectomy for seizure control with a resultant postoperative right internal
      capsule infarct.

PMID- 29184719
TI  - Diabetes and morbid obesity are associated with higher reoperation rates
      following microvascular decompression surgery: An ACS-NSQIP analysis.
AB  - Background: Microvascular decompression (MVD) is the preferred treatment for
      refractory trigeminal neuralgia, hemifacial spasm, and glossopharyngeal
      neuralgia. Despite its high rate of success, MVD carries risk of complications.
      In this study, we examine outcomes following MVD and identify risk factors
      associated with adverse outcomes. Methods: A review of the American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was
      performed with CPT code 61458 queried between 2007 and 2014. Demographics,
      preoperative comorbidities, and 30-day outcomes were analyzed. Univariate and
      multivariate regression analyses were performed to identify predictors of
      reoperation and adverse events. Results: Five hundred and six craniotomies were
      studied. Nineteen (5.5%) instances of 30-day readmission were reported, with 14
      (2.8%) patients returning to the operating room. No instances of death or
      hemorrhage requiring operation were reported. Morbid obesity (body mass index
      >40) (P = 0.030) and diabetes (P = 0.017) were associated with risk of
      reoperation. Age, operative time, and indication for surgery were not associated
      with significant differences in adverse events. Conclusions: MVD is a common and
      effective procedure with a relatively safe profile and low 30-day risk of
      reoperation. Advanced age is not associated with worse outcomes. Obesity and
      diabetes, however, are associated with increased risk of reoperation and may
      warrant additional precautions.

PMID- 29184721
TI  - Facial Contouring Surgery-Malarplasty.
AB  - Supplemental Digital Content is available in the text.

PMID- 29184720
TI  - Risk factors for wound complications following spine surgery.
AB  - Background: Wound complications, including surgical site infections (SSIs) and
      wound dehiscence, are among the most common complications following spine surgery
      often leading to readmission. The authors sought to identify preoperative
      characteristics predictive of wound complications after spine surgery. Methods:
      The American College of Surgeons National Surgical Quality Improvement Program
      database for years 2012-2014 was reviewed for patients undergoing spine surgery,
      defined by the Current Procedural Terminology codes. Forty-four preoperative and
      surgical characteristics were analyzed for associations with wound complications.
      Results: Of the 99,152 patients included in this study, 2.2% experienced at least
      one wound complication (superficial SSI: 0.9%, deep SSI: 0.8%, organ space SSI:
      0.4%, and dehiscence: 0.3%). Multivariate binary logistic regression testing
      found 10 preoperative characteristics associated with wound complications: body
      mass index >=30, smoker, female, chronic steroid use, hematocrit <38%, infected
      wound, inpatient status, emergency case, and operation time >3 hours. A risk
      score for each patient was created from the number of characteristics present.
      Receiver operating characteristic curves of the unweighted and weighted risk
      scores generated areas under the curve of 0.701 (95% CI: 0.690-0.713) and 0.715
      (95% CI: 0.704-0.726), respectively. Patients with unweighted risk scores >7 were
      25-fold more likely to develop a wound complication compared to patients with
      scores of 0. In addition, mortality rate, reoperation rate, and total length of
      stay each increased nearly 10-fold with increasing risk score. Conclusion: This
      study introduces a novel risk score for the development of wound dehiscence and
      SSIs in patients undergoing spine surgery, using new risk factors identified
      here.

PMID- 29184722
TI  - Facial Contouring Surgery-Mandibuloplasty: Genioplasty and Mandible Angle
      Correction.
AB  - Supplemental Digital Content is available in the text.

PMID- 29184723
TI  - Patient-Reported Outcomes following Split-Face Injection of 2 Volumizing Fillers
      in the Upper Cheeks.
AB  - Background: Patient-reported outcomes are important measures when assessing the
      efficacy of aesthetic procedures. Objective: To compare outcomes between 2
      volumizing hyaluronic acid fillers. Materials and Methods: Subjects with moderate
      to-severe volume loss in the cheeks were randomized in a split-face design to
      malar enhancement with Cohesive Polydensified Matrix 26 mg/ml HA (CPM-26) and
      Vycross 20 mg/ml HA (VYC-20). The same injection technique and injection volume
      were applied for both sides of the face. Anesthetics, overcorrection, and touch
      ups were not permitted. Blinded subjects assessed aesthetic improvements using
      the Global Aesthetic Improvement Scale and treatment satisfaction by confirming
      their willingness to repeat treatment or recommend it to friends. Follow-up was
      18 months. Results: A total of 45 subjects received a single 2 mL injection of
      CPM-26 on one side and VYC-20 on the contralateral side of the face. The
      proportion of subjects reporting improvement on the Global Aesthetic Improvement
      Scale compared with baseline for CPM-26 and VYC-20 was 97.7% and 88.6%,
      respectively, at 3 months, 73.8% and 71.1% at 12 months, and 61.0% and 56.7% at
      18 months. Treatment satisfaction was high, with the majority of subjects stating
      that they would repeat treatment and recommend it to friends, but at each time
      point, a higher proportion of subjects was more satisfied with the CPM-26-treated
      side of the face. Conclusions: In this first direct comparison of CPM-26 and VYC
      20, the majority of subjects were satisfied with both treatments throughout the
      study. Patient-reported outcome measures identified a trend in favor of CPM-26.

PMID- 29184724
TI  - An Algorithmic Approach to Operative Management of Complex Pediatric Dog Bites: 3
      Year Review of a Level I Regional Referral Pediatric Trauma Hospital.
AB  - Background: Incidence of dog bites continues to rise among the pediatric
      population and serves as a public health threat for the well-being of children.
      Plastic surgeons are at the forefront of initial management and eventual outcome
      of these devastating injuries. This study set out to determine the nature of dog
      bite injuries treated over a 3-year period at a large level 1 pediatric trauma
      center. Methods: A retrospective review of emergency room records of all
      pediatric patients (age, 0-18 years old) who sustained dog bites between January
      2012 and December 2014 were gathered. All details about age of patient, location
      and severity of dog bites, type of dog breed, antibiotics given, and emergency
      versus operative treatment were recorded and analyzed. Results: One hundred eight
      patients aged 5 months to 18 years old were treated in the emergency department
      after suffering dog bite injuries during the study period. The highest incidence
      of dog bites occurred in preschool children. The mean age for patients who
      required operative repair was lower than the mean age for patients who underwent
      primary closure in the emergency department. The location of injury was most
      commonly isolated to the head/neck region. Of the 56 cases that had an identified
      dog breed, pit bulls accounted for 48.2% of the dog bites, and 47.8% of pit bull
      bites required intervention in the operating room. Conclusion: Children with
      large dog bite injuries require more immediate care in a level 1 pediatric trauma
      hospitals in order to optimize their hospitalization course and eventual outcome.

PMID- 29184725
TI  - Video Tutorial for Clinical Flap-Monitoring in Plastic Surgery.
AB  - Supplemental Digital Content is available in the text.

PMID- 29184726
TI  - Occlusal Plane Altering 2 Jaw Surgery Based on the Clockwised Rotational Surgery
      First Orthognathic Approach.
AB  - Supplemental Digital Content is available in the text.

PMID- 29184727
TI  - Preliminary Study of PGA Fabric for Seromas at Latissimus Dorsi Flap Donor Sites.
AB  - Background: Seroma formation is a major complication following latissimus dorsi
      (LD) flap transfer for breast reconstruction. We implanted a nonwoven
      polyglycolic acid (PGA) fabric-a biodegradable polymer-in the LD flap donor site
      and examined its effect on postoperative seroma formation and resolution in a
      comparative study on 38 patients undergoing primary 1-stage breast reconstruction
      by LD flap. Method: A PGA treatment group had a PGA fabric placed in the donor
      wound (PGA group, n = 20), whereas a second group was treated with standard donor
      site closure (control group, n = 18). The incidence of seromas was comparable
      between the groups. Result: There was a significant reduction in aspiration
      volume by needle aspiration after drain removal (P < 0.05) and in the time until
      seroma resolution (P < 0.01) in the PGA group compared with the control group.
      Conclusion: These results indicate that application of PGA at the LD donor site
      is useful in controlling postoperative seromas.

PMID- 29184728
TI  - DIEP Flap Breast Reconstruction in Patients with Breast Ptosis: 2-Stage
      Reconstruction Using 3-Dimensional Surface Imaging and a Printed Mold.
AB  - Background: Autologous breast reconstruction can be performed for breasts with
      ptosis to a certain extent, but if patients desire to correct ptosis, mastopexy
      of the contralateral breast is indicated. However, accurate prediction of post
      mastopexy breast shape is difficult to make, and symmetrical breast
      reconstruction requires certain experience. We have previously reported the use
      of three-dimensional (3D) imaging and printing technologies in deep inferior
      epigastric artery perforator (DIEP) flap breast reconstruction. In the present
      study, these technologies were applied to the reconstruction of breasts with
      ptosis. Methods: Eight breast cancer patients with ptotic breasts underwent two
      stage unilateral DIEP flap breast reconstruction. In the initial surgery, tissue
      expander (TE) placement and contralateral mastopexy are performed simultaneously.
      Four to six months later, 3D bilateral breast imaging is performed after
      confirming that the shape of the contralateral breast (post-mastopexy) is
      somewhat stabilized, and a 3D-printed breast mold is created based on the mirror
      image of the shape of the contralateral breast acquired using analytical
      software. Then, DIEP flap surgery is performed, where the breast mold is used to
      determine the required flap volume and to shape the breast mound. Results: All
      flaps were engrafted without any major perioperative complications during both
      the initial and DIEP flap surgeries. Objective assessment of cosmetic outcome
      revealed that good breast symmetry was achieved in all cases. Conclusions: The
      method described here may allow even inexperienced surgeons to achieve
      reconstruction of symmetrical, non-ptotic breasts with ease and in a short time.
      While the requirement of two surgeries is a potential disadvantage, our method
      will be particularly useful in cases involving TEs, i.e., delayed reconstruction
      or immediate reconstruction involving significant skin resection.

PMID- 29184729
TI  - Combined Tongue Flap and Deepithelialized Advancement Flap for Thick Lower Lip
      Reconstruction.
AB  - We repaired a long horizontal defect in the lower lip caused by the resection of
      squamous cell carcinoma by reconstructing the white lip with a V-Y advancement
      flap and vermilion with a tongue flap. During this procedure, we deepithelialized
      the V-Y flap, lifted the upper margin of the flap and sutured it to the remaining
      upper margin of the lip, and then covered it with the tongue flap, resulting in
      the successful reconstruction of a thick lip. There were no postoperative
      complications in articulation or swallowing. This novel procedure is a simple
      method to aesthetically and functionally reconstruct a thick lower lip.

PMID- 29184730
TI  - Outcomes Comparison for Microsurgical Breast Reconstruction in Specialty Surgery
      Hospitals Versus Tertiary Care Facilities.
AB  - Background: Postoperative monitoring is crucial in the care of free flap breast
      reconstruction patients. Tertiary care facilities (TCFs) provide postoperative
      monitoring in an ICU after surgery. Specialty surgery hospitals (SSHs) do not
      have ICUs, but these facilities perform free flap breast reconstruction as well.
      Are outcomes comparable between the 2 facilities in terms of flap reexploration
      times and overall success? Methods: Retrospective study including 163 SSH and 157
      TCF patients. Primary predictor was facility in which the procedure was
      performed. Secondary predictors included operative, demographic, and comorbidity
      data. Primary outcomes were flap take back rate and flap failures. Secondary
      outcomes were total time from adverse event noticed in the flap to returning to
      the operating room (OR) and total time from decision made to return to the OR to
      returning to the OR (decision made). Tertiary outcomes were length of stay,
      operative times, and blood loss. Results: Patients at the TCF were generally less
      healthy than SSH patients. Salvage rates and failure rates were similar between
      the 2 institutions. Adverse event noticed and decision made times did not differ
      between the 2 facilities. Overall flap success rate was 98.22% at SSH and 98.81%
      at TCF. No primary or secondary predictors had a significant correlation with
      increased odds for flap failure. Conclusion: SSHs can offer similar outcomes in
      free flap breast reconstruction with just as effective clinical response times to
      endangered flaps as found in a TCF. However, surgery at an SSH may best be
      reserved for healthier patients.

PMID- 29184731
TI  - Tracheocutaneous Fistula Closure with Turnover Flap and Polydioxanone Plate.
AB  - An alternative surgical treatment is proposed for closure of tracheocutaneous
      fistulas. The authors present a new technique for reconstruction of persistent
      tracheocutaneous fistula resultant from temporary tracheostomy. The single-stage
      closure under local anesthesia involves a fistulous tract turnover flap with a
      perforated 0.15 mm polydioxanone plate between the flap and the subcutaneous
      closure. This article presents 3 cases of persistent tracheocutaneous fistula
      treated by this method. At follow-up examination after follow-up, no recurrent
      fistula formation had occurred, and no respiratory deformity was present.

PMID- 29184732
TI  - Depressive Symptoms among Plastic Surgery Residents.
AB  - Background: A literature review did not reveal any study investigating the
      prevalence of depression among plastic surgery residents. Methods: We conducted a
      cross-sectional mail survey and included all Saudi Plastic Surgery residents in
      our local program in Saudi Arabia. The Beck Depression Inventory II was used.
      Results: The inventory showed that mild, moderate, and severe depressive symptoms
      were prevalent in 20.6%, 38.2%, and 11.8%, respectively. Junior residents were
      more prone to depression. Conclusions: The high prevalence rate of depression
      among plastic surgery residents is alarming, and further studies are warranted.
      The problem has received no attention in the plastic surgery literature.

PMID- 29184733
TI  - Erratum: Donor-Site Morbidity After DIEAP Flap Breast Reconstruction-A 2-Year
      Postoperative Computed Tomography Comparison: Erratum.
AB  - [This corrects the article DOI: 10.1097/GOX.0000000000001405.].

PMID- 29184734
TI  - The Delay Phenomenon: Is One Surgical Delay Technique Superior?
AB  - Background: Surgical delay remains a common method for improving flap survival.
      However, the optimal surgical technique has not been determined. In this article,
      we compare flap perfusion, viable surface area, and flap contraction of 2
      surgical delay techniques. Methods: Male Sprague-Dawley rats were divided into 3
      groups. In the incisional surgical delay group (n = 9), a 9 * 3 cm dorsal flap
      was incised on 3 sides without undermining, leaving a cranial pedicle. In the
      bipedicle surgical delay group (BSD, n = 9), a 9 * 3 cm dorsal flap was incised
      laterally and undermined, leaving cranial and caudal pedicles. Control group (n =
      16) animals did not undergo a delay procedure. Ten days following surgical delay,
      all flaps for all groups were raised, leaving a cranial pedicle. A silicone sheet
      separated the flap and the wound bed. On postoperative day (POD) 7, viable
      surface area was determined clinically. Contraction compared to POD 0 was
      measured with ImageJ software. Perfusion was measured with Laser Doppler Imaging.
      The Kruskal-Wallis with Dunn's multiple comparisons test was performed for group
      comparisons. Results: BSD preserved significantly more viable surface area on POD
      7 (13.7 +/- 4.5 cm2) than Control (8.7 +/- 1.8 cm2; P = 0.01). BSD also showed
      significantly less contraction (21.0% +/- 13.5%) than Control (45.9% +/- 19.7%; P
      = 0.0045). BSD and incisional surgical delay showed significantly increased
      perfusion compared with Control on POD 0 (P = 0.02 and 0.049, respectively),
      which persisted on POD 3. This trend resolved by POD 7. Conclusion: BSD showed
      improved early perfusion, increased viable surface area, and reduced contraction
      compared to control, suggesting that BSD is the superior flap design for
      preclinical modeling.

PMID- 29184735
TI  - Association of High-Volume Surgeons Working in High-Volume Hospitals with Cost of
      Free Flap Surgeries.
AB  - Background: We examined the associations of surgeon and hospital volume with
      total cost, length of stay (LOS), and cost per day for free tissue transfer (FTT)
      surgeries. Evidence demonstrates a higher likelihood of success for FTT in higher
      volume hospitals. Little, however, is known about volume-outcome associations for
      surgical costs and LOS. We hypothesized that higher provider volume is associated
      with lower cost and shorter LOS. Methods: Using Taiwan's national data (2001
      2012), we conducted a retrospective cohort study of all adults 18-64 years of age
      who underwent FTT during the study period. We used hierarchical regression
      modeling for our analyses. Our 3 outcome variables were total cost of FTT
      surgery, LOS in hospital, and cost per day. Results: Except for functional muscle
      flap, in which LOS was 12 days shorter in high-volume compared with low-volume
      hospitals (P = 0.017), no association between hospital volume and LOS was found.
      Contrary to our hypothesis, our results for all FTT cases demonstrate positive
      associations of medium-volume hospitals (OR = 1.31; CI, 1.11-1.55) and high
      volume surgeons (OR = 1.16; CI,1.03-1.32) with total cost and cost per day,
      respectively. The interactions of hospital volume and surgeon volume show that in
      medium- and high-volume hospitals, surgeons with the highest volume had the
      lowest predicted cost per day among hospitals in that category; but all
      differences in cost were small. Conclusions: There were no substantial variations
      based on different hospital or surgeon volume in LOS, total cost, or cost per day
      for FTT operations performed in Taiwan.

PMID- 29184736
TI  - The Reconstruction of the Donor Site of DP Flap Using Thoracodorsal Artery
      Perforator Flap.
AB  - We performed a new procedure for reconstruction of donor site of a deltopectoral
      (DP) flap. A 58-year-old man presented with a wide subcutaneous abscess, which
      was caused by acute mandibular osteomyelitis due to dental caries. On admission,
      the patient received a neck incision for drainage. However, necrosis of the neck
      skin was observed after drainage. The patient had an 8 * 10 cm skin and soft
      tissue defect, which we covered with a DP flap (15 * 7 cm). The DP flap donor
      site was reconstructed using a 16 * 8 cm pedicled thoracodorsal artery perforator
      (TDAP) flap. There was no flap necrosis, abscess formation, or scar contracture
      of the DP region. Debulking of the TDAP flap was not required. The pedicled TDAP
      flap is useful for the reconstruction of the donor site of DP flap. In this
      report, we describe our operative procedure.

PMID- 29184737
TI  - The Idea of Beauty and Its Biases: Critical Notes on the Aesthetics of Plastic
      Surgery.
AB  - Two biases affect the idea of beauty often embodied in aesthetic surgery. The
      first one is that the living body is the sum of different parts; the second one
      claims that beauty results from the sum of beautiful elements. Taken together,
      these 2 biases explain most of the aesthetic surgery procedures, in which a
      localized improvement is supposed to impact on the whole body image. In this
      article, I put into question these 2 problematic assumptions, showing that
      Western and Eastern aesthetics, on one side, and philosophical reflections, on
      the other side, support a different conception of beauty. In particular, an
      alternative idea that opens to authenticity and imperfection and focuses on the
      living body rather than on the mere anatomical surface is proposed here as a more
      adequate concept of beauty for aesthetic surgery.

PMID- 29184738
TI  - Nasal Duplication Combined with Cleft Lip and Palate: Surgical Correction and
      Long-Term Follow-Up.
AB  - Background: Diprosopus dirrhinus, or nasal duplication, is a rare entity of
      partial craniofacial duplication. Methods: The case we present is the first
      report of diprosopus dirrhinus associated with complete cleft lip and palate. The
      baby was born in Cambodia at full term by normal vaginal delivery with no
      significant perinatal and family history. Physical examination revealed
      significant facial deformity due to the duplicated nose and the left complete
      cleft lip/palate on the right subset. Results: There were 4 nostrils; both medial
      apertures including the cleft site were found to be 10-15 mm deep cul-de-sac
      structures without communication to the nasopharynx. The upper third of the face
      was notable for hypertelorism with a duplication of the soft-tissue nasion and
      glabella. Between the 2 nasal dorsums, there was a small cutaneous depression
      with a lacrimal fistula in the midline. Surgical treatment included the first
      stage of primary lip and nose repair and the second stage of palatoplasty.
      Conclusions: The patient was followed up at the age of 10 years showing
      satisfactory results for both aesthetic and functional aspects. Further
      management in the future will be required for the hypertelorism and nasal
      deformity.

PMID- 29184739
TI  - Review of 494 Consecutive Breast Augmentation Patients: System to Improve Patient
      Outcomes and Satisfaction.
AB  - Background: Breast augmentation continues to be one of the most common surgical
      procedures performed by plastic surgeons. As implant options expand, controlling
      the numerous variables required for a successful result will prove increasingly
      challenging. The purpose of this study was to outline specific steps that can be
      taken during the patient consultation and during surgery to decrease
      complications and improve overall patient satisfaction and patient outcomes.
      Methods: A retrospective review of 494 consecutive patients who underwent primary
      augmentation mammaplasty performed by a single surgeon was undertaken. Surgical
      outcomes were recorded and compared with previously published results. Patient
      satisfaction was measured using the BREAST-Q Augmentation Module. Results:
      Patients were followed for an average of 6 months (range, 0-45 months). Of the
      494 patients, 1.3% developed capsular contracture. Other complications included
      0.6% asymmetry, 0.4% malposition, 0.2% hematoma, and 0.2% rippling. The median
      BREAST Q score for the patient's overall satisfaction with outcome was 86%. The
      median BREAST Q score for patient's satisfaction with the plastic surgeon,
      medical team, and office staff was 100% in each case. The median score for
      psychological well-being, physical well-being, and sexual well-being was 100%,
      90%, and 88%, respectively. Conclusions: The system outlined in this study showed
      very low rates of complications and high scores for patient satisfaction.
      Following a system like this will become increasingly important as breast
      augmentation continues to become more popular, implant options continue to
      expand, and social media continues to be used by patients to share surgical
      experiences.

PMID- 29184740
TI  - Can Friedberg's Triad Solve Persistent Anesthesia Problems? Over-Medication, Pain
      Management, Postoperative Nausea and Vomiting.
AB  - Friedberg's Triad is (1) measure the brain; (2) preempt the pain; (3) emetic
      drugs abstain. Persistent anesthesia problems include over- and under-medication,
      postoperative pain management, and postoperative nausea and vomiting. Inspired by
      Vinnik's diazepam-ketamine paradigm, Friedberg's propofol ketamine paradigm was
      first published in 1993. The 1997 addition of the bispectral (BIS) index brain
      monitor made the propofol ketamine paradigm numerically reproducible. The 1998
      addition of the frontalis electromyogram (EMG) as a secondary trend to the BIS
      transformed the time-delayed BIS monitor into a real-time, extremely useful
      device. Before BIS monitoring, anesthesiologists only had heart rate (HR) and
      blood pressure (BP) changes to guide depth of anesthesia. Not surprisingly, the
      American Society of Anesthesiologists' Awareness study showed no HR or BP changes
      in half of the patients experiencing awareness with recall. HR and BP changes may
      only reflect brain stem signs while consciousness and pain are processed at
      higher, cortical brain levels. BIS/electromyogram measurement can accurately
      reflect propofol effect on the cerebral cortex in real time. Although propofol
      requirements can vary as much as a hundred-fold, titrating propofol to 60 < BIS <
      75 with baseline electromyogram assures every patient will be anesthetized to the
      same degree and allows more scientific analysis of outcomes. Numerous
      publications are cited to support the author's 25-year clinical experience. Over
      that period, no office-based, cosmetic surgery patients were admitted to the
      hospital for unmanageable pain or postoperative nausea and vomiting. Friedberg's
      Triad appears to solve persistent anesthesia problems.

PMID- 29184741
TI  - Psychometric Validation of the BODY-Q in Danish Patients Undergoing Weight Loss
      and Body Contouring Surgery.
AB  - Background: A well-developed patient-reported outcome instrument is needed for
      use in Danish bariatric and body contouring patients. The BODY-Q is designed to
      measure changes in important patient outcomes over the entire patient journey,
      from obesity to post-body contouring surgery. The current study aims to
      psychometrically validate the BODY-Q for use in Danish patients. Methods: The
      process consisted of 3 stages: translation and linguistic validation, field-test,
      and data analysis. The translation was performed in accordance with the
      International Society for Pharmacoeconomics and Outcomes Research and World
      Health Organization guidelines, and field-test data were collected in 4
      departments in 2 different hospitals. Field-test data were analyzed using Rasch
      Measurement Theory. Results: A total of 495 patients completed the Danish BODY-Q
      field-test 1-4 times, leading to a total of 681 assessments with an overall
      response rate at 76%. Cronbach alpha values were >= 0.90, and person separation
      index values were in general high. The Rasch Measurement Theory analysis provided
      broad support for the reliability and validity of the Danish version of the BODY
      Q scales. Item fit was outside the criteria for 34 of 138 items, and of these, 21
      had a significant chi-square P value after Bonferroni adjustment. Most items (128
      of 138) had ordered thresholds, indicating that response options worked as
      intended. Conclusion: The Danish version of the BODY-Q is a reliable and valid
      patient-reported outcome instrument for use in Danish bariatric and body
      contouring patients.

PMID- 29184742
TI  - A Breast Reconstruction Using a Breast Prosthesis and Capsular Flap for a
      Lymphocele Patient.
AB  - We encountered a very rare condition where the patient had a lymphocele under the
      skin envelope of the breast following mastectomy during the course of breast
      reconstruction with a tissue expander. The incidence rate of axillary lymphoceles
      is reported as 2.2-50% in breast cancer patients, but there have been no reports
      mentioning lymphoceles under the breast skin during the course of breast
      reconstruction with a prosthesis. The patient had a lymphocele in the lower
      lateral part of the breast following mastectomy and had multiple cellulitis-like
      inflammations. These inflammations were treated with conservative therapy such as
      administration of antibiotics, resting, and cooling. After 6 months of the
      initial surgery, the patient underwent complete resection of the lymphocele,
      preventative elimination of a possible lymphatic leakage, and breast
      reconstruction using a prosthesis combined with a capsular flap. The capsular
      flap is a transposition flap that uses capsular tissue around the expander to
      cover adjacent thinned skin. There were no postoperative complications such as
      breast skin necrosis, exposure of the prosthesis, or recurrence of the lymphocele
      and cellulitis. The patient had a successful breast reconstruction even though a
      lymphocele of the breast was observed. Even though a patient may have a
      lymphocele in the breast following mastectomy, with careful resection of the
      lymphocele, complete elimination of possible lymphatic leakage, and by performing
      the capsular flap technique, complete breast reconstruction with a breast
      prosthesis may be successful.

PMID- 29184743
TI  - Infectious Complications following Breast Reconstruction Using Tissue Expanders
      in Patients with Atopic Dermatitis.
AB  - Infectious complications represent one of the most prominent factors contributing
      to tissue expander (TE) loss in breast reconstruction procedures. Several patient
      characteristics that increase the risk for surgical-site infection or TE
      infection have been reported, but no study has focused on the relationship
      between atopic dermatitis (AD) and TE infection or surgical-site infection.
      Recently, we investigated 203 cases of breast reconstruction surgeries performed
      using TEs and noted that all 3 patients who had AD developed infectious
      complications that ultimately led to TE removal. Considering its pathophysiology,
      it is likely that patients with AD relatively easily develop infectious
      complications due to barrier dysfunction, abnormalities in innate immune
      responses, or colony formation by Staphylococcus aureus. Particular caution
      should be exercised for breast reconstruction using man-made materials in cases
      complicated by AD.

PMID- 29184744
TI  - Multidirectional Cranial Distraction Osteogenesis with Simplified Modifications
      for Treating Sagittal Synostosis.
AB  - Background: Multidirectional cranial distraction osteogenesis (MCDO) is a
      procedure of ours developed earlier for treating craniosynostosis. However, the
      numerous bone flaps led to prolonged operative time and occasional bone
      detachment from dura. We have since simplified the osteotomy design. In treating
      sagittal synostosis, required bone flaps have been reduced to 11 (from ~20).
      Methods: In a 2-year period (2014-2015), 5 boys with sagittal synostosis
      underwent MCDO using our simplified and fixed-form osteotomy. Mean age at surgery
      was 9.4 months (range, 8-11 months). Pre- and postoperative cranial morphology
      was assessed by cephalic index and by mid-sagittal vector analysis. Results:
      Improved cranial shape was confirmed by 3-dimensional CT scans and by mid
      sagittal vector index. Mean preoperative cephalic index (68.7) progressively
      increased to means of 78.5 immediately after distraction device removal, 75.2 at
      postoperative month 6, and 75.1 at 1 year postoperatively. There were no major
      complications, although transient cerebrospinal fluid leakage and loosening of
      anchor pins occurred in 1 patient. Conclusions: Simplified MCDO has a number of
      advantages over conventional distraction procedures such as discretionary
      reshaping/expansion of cranium and predictable osteogenesis and is a valid
      treatment option for patients with sagittal synostosis.

PMID- 29184745
TI  - Solving Hand/Finger Pain Problems with the Pencil Test and Relative Motion
      Splinting.
AB  - Supplemental Digital Content is available in the text.

PMID- 29184747
TI  - Intravenous Access in Infants Undergoing Bilateral Sural Nerve Grafts for Primary
      Brachial Plexus Exploration.
AB  - Background: Intravenous access (IVA) in infants undergoing primary brachial
      plexus exploration may be difficult. Both lower limbs are prepared and draped for
      sural nerve graft harvesting. The injured upper limb is also prepared and draped
      and is not available for IVA. In difficult IVA from the remaining upper limb, we
      have been using one of the feet for IVA. The infection rate and problems of
      intravenous infusions in this setting have never been studied in the literature.
      This study documents the infection rate and problems of intravenous infusions in
      these infants when a foot (within the sterile field) is used for IVA. Methods:
      This is a retrospective study of 63 consecutive infants undergoing primary
      brachial plexus exploration, and in whom IVA was obtained from one of the feet.
      Infection rate and problems of intravenous infusions were recorded. Results: No
      surgical wound infection and no infection of the IVA site were noted. There were
      no instances of accidental dislodgement of the intravenous cannula and no
      instances of extravasation. Conclusion: The use of one of the feet (within the
      sterile filed) for IVA is safe and acceptable in infants undergoing primary
      brachial plexus exploration and bilateral sural nerve grafting.

PMID- 29184746
TI  - Strategies for Reducing Fatal Complications in Liposuction.
AB  - Background: Liposuction has become one of the most common cosmetic surgical
      procedures, and severe complications secondary to this procedure have also
      increased significantly. That is why we carry out a research work to know the
      most frequent severe complications reported in the scientific literature to
      indicate criteria for prevention. Methods: English-language scientific
      publications about liposuction and its complications were analyzed using the
      PubMed.gov, from the beginning of PubMed's history through June 10, 2017. Five
      terms were used to define liposuction and its complications: "liposuction,"
      "liposuction AND complications," liposuction AND major complications,"
      "liposuction AND complications AND death," and "liposuction AND death." The
      quantities of results for the 5 phrases were analyzed, along with their contents.
      Results: One thousand sixty-three results were obtained from 1973 through June
      10, 2017 for the phrase "Liposuction and Complications" in humans; for
      "Liposuction and Major Complications," 153 articles were found; for "Liposuction
      and Deaths," 89 articles were found; and 42 articles were obtained with the terms
      "Liposuction and Major Complications and Deaths." After final depuration, all
      those that were not specific to severe liposuction complications were eliminated,
      leaving a total of 39 articles that were included in our study. Five problems
      proved to be the most serious complications when performing liposuction:
      Thromboembolic disease, fat embolism, pulmonary edema, lidocaine intoxication,
      and intraabdominal visceral lesion. Conclusions: The 5 most important
      complications that can cause death in liposuction are easily preventable using
      simple measures and proper safety protocols that are described in this work.

PMID- 29184748
TI  - Filling the Spectrum Expander with Air-A New Alternative.
AB  - The Spectrum adjustable saline implant is optimal for prepectoral breast
      reconstruction as it can be placed virtually empty and thus flat, applying no
      pressure on the overlying skin flap. However, when saline is added, it tends to
      pool at the bottom of the implant resulting in its uneven surface and rippling.
      Air filling results in the uniform distribution within the implant shell and
      smooth even implant surface, which facilitates acellular dermal matrix adhesion.
      Pressure to the skin flap is averted, patients are more comfortable, and rippling
      is not seen.

PMID- 29184749
TI  - Pedicle-to-Perforator Bypass Using Supermicrosurgical Technique for Deep Inferior
      Epigastric Artery Perforator Flap Salvage.

PMID- 29184750
TI  - Long-Term Patency of Twisted Vascular Pedicles in Perforator-Based Propeller
      Flaps.
AB  - Background: Propeller flaps require torsion of the vascular pedicle of up to 180
      degrees. Contrary to free flaps, where the relevance of an intact vascular
      pedicle has been documented, little is known regarding twisted pedicles of
      propeller flaps. As secondary surgeries requiring undermining of the flap are
      common in the extremities, knowledge regarding the necessity to protect the
      pedicle is relevant. The aim of this study was a long-term evaluation of the
      patency of vascular pedicle of propeller flaps. Methods: In a retrospective
      clinical study, 22 patients who underwent soft-tissue reconstruction with a
      propeller flap were evaluated after 43 months. A Doppler probe was used to locate
      and evaluate the patency of the vascular pedicle of the flap. Results: The flaps
      were used in the lower extremity in 19 cases, on the trunk in 3 cases. All flaps
      had healed. In all patients, an intact vascular pedicle could be found. Flap
      size, source vessel, or infection could therefore not be linked to an increased
      risk of pedicle loss. Conclusions: The vascular pedicle of propeller flaps
      remains patent in the long term. This allows reelevation and undermining of the
      flap. We therefore recommend protecting the pedicle in all secondary cases to
      prevent later flap loss.

PMID- 29184751
TI  - A New Modified Method of Correcting Cryptotia with a Subcutaneous Pedicled Flap.
AB  - We developed a surgical technique to correct cryptotia using a subcutaneous
      pedicled flap raised from the retroauricular region. A skin paddle over the
      caudal part of the auricular sulcus is designed and transferred to the skin
      defect of the upper posterior surface of the auricle. This procedure has been
      performed on 17 ears in 14 patients with cryptotia since 1992. There were no
      postoperative complications, such as necrosis of the flaps or deformities, and
      cryptotia did not recur in any patient. A satisfactory auricular contour with a
      sufficiently deep auriculotemporal sulcus was preserved in all cases. The
      intraoperative procedure to correct cryptotia and outcomes obtained are presented
      herein and compared with other procedures.

PMID- 29184752
TI  - Anatomical Analysis of Cutaneous Perforator Distribution in the Forearm.
AB  - Background: Few reports describe the distribution of cutaneous perforators from
      the radial and ulnar arteries in the forearm. This study aimed to map the
      location of the cutaneous perforators that arise directly from the radial and
      ulnar arteries in cadavers. Methods: Twenty-nine human cadaveric forearms were
      dissected. All radial and ulnar arteries cutaneous perforators were analyzed for
      total number and distribution. To define the distribution of each cutaneous
      perforator, the forearm was divided into 10 sections, with the sections labeled
      as 10%, 20%, 30%, and so on, beginning at the wrist. Results: From the radial
      artery, there were a total of 262 skin perforators with an average of 9.03 +/-
      2.28 (mean +/- SD) per limb, whereas the total was 159 from the ulnar artery,
      with an average of 5.48 +/- 1.49 per limb. Additionally, 128 (49%) radial artery
      cutaneous perforators and 75 (47%) from the ulnar artery were concentrated in the
      0-30% section of the forearm. Both the radial and ulnar arteries had many
      cutaneous perforators in the forearm section labeled 70%, with 32 of 262 (12%)
      cutaneous perforators of the radial artery and 27 of 159 (17%) cutaneous
      perforators of the ulnar artery located here. Conclusions: There were more
      cutaneous perforators from the radial artery than from the ulnar artery, and both
      were concentrated in the distal one-third of the forearm and in the forearm
      section labeled 70%. This information could be helpful when harvesting forearm
      flaps.

PMID- 29184753
TI  - Tissue Augmentation with Allograft Adipose Matrix For the Diabetic Foot in
      Remission.
AB  - Background: Repetitive stress on the neuropathic plantar foot is the primary
      cause of diabetic foot ulcers. After healing, recurrence is common. Modulating
      plantar pressure has been associated with extension of ulcer free days.
      Therefore, the goal of this study was to determine the effects of an injectable
      allograft adipose matrix in providing a protective padding and reducing the
      pressure in the plantar foot. Methods: After healing his recurrent ulcer using
      total contact casting, a 71-year-old man with a 9-year history of recurrent
      diabetic foot ulcers was treated with injection of allograft adipose matrix,
      procured from donated human tissue. This was delivered under postulcerative
      callus on the weight-bearing surface of the distal end of the first ray
      resection. As is standard in our clinic for tissue augmentation procedures, our
      patient underwent serial plantar pressure mapping using an in-shoe pressure
      monitoring system. Results: There was a 76.8% decrease in the mean peak pressure
      due to the fat matrix injected into the second metatarsal region and a 70.1%
      decrease in mean peak pressure for the first ray resection at the site of the
      postulcerative callus. By 2 months postoperatively, there was no evidence of
      residual callus. This extended out to the end of clinical follow-up at 4 months.
      Conclusion: The results from this preliminary experience suggest that allograft
      adipose matrix delivered to the high risk diabetic foot may have promise in
      reducing tissue stress over pre- and postulcerative lesions. This may ultimately
      assist the clinician in extending ulcer-free days for patients in diabetic foot
      remission.

PMID- 29184754
TI  - Summer crisis in Iran: increase in reported cases of Crimean-Congo Hemorrhagic
      Fever (CCHF).

PMID- 29184755
TI  - Dissemination of high-level mupirocin-resistant CC22-MRSA-IV in Saxony.
AB  - Mupirocin is used for eradicating methicillin-resistant S. aureus (MRSA) in nasal
      colonization. A plasmid-borne gene, mupA, is associated with high-level mupirocin
      resistance. Despite the fact that, among all MRSA from a tertiary care center in
      the German state of Saxony, the prevalence of mupA, encoding high-level mupirocin
      resistance, was approximately 1% over a 15-year period from 2000-2015, a sharp
      increase to nearly 20% was observed in 2016/2017. DNA microarray profiling
      revealed that this was due to the dissemination of a variant of CC22-MRSA-IV
      ("Barnim Epidemic Strain" or "UK-EMRSA-15"), which, in addition to mecA, harbors
      mupA, aacA-aphD, qacA, and - in most isolates - erm(C). In order to prevent
      therapy failures and a further spread of this strain, the use of mupirocin should
      be more stringently controlled as well as guided by susceptibility testing. In
      addition, MRSA decolonization regimens that rely on other substances, such as
      betaisodona, polyhexanide or octenidine, should be considered.

PMID- 29184757
TI  - Biomechanical assessment of new surgical method instead of kyphoplasty to improve
      the mechanical behavior of the vertebra: Micro finite element study.
AB  - AIM: To reduce post treatments of kyphoplasty, as a common treatment for
      osteoporotic vertebrae. METHODS: This study suggests a new method for treating
      vertebrae by setting the hexagonal porous structure instead of the rigid bone
      cement mass in the kyphoplasty (KP). The KP procedure was performed on the fresh
      ovine vertebra of the level L1. Micro finite element modeling was performed based
      on micro computed tomography of ovine trabecular cube. The hexagonal porous
      structure was set on one cube instead of the bone cement mass. For the implant
      designing, two geometrical parameters were considered: Spacing diameter and
      thickness. RESULTS: The results of micro finite element analyses indicated the
      improvement in the mechanical behavior of the vertebra treated by the hexagonal
      porous structures, as compared to those treated by vertebroplasty (VP) and KP
      under static loading. The improvement in the mechanical behavior of the vertebra,
      was observed as 54% decrease in the amount of maximum Von Misses stress
      (improvement of stress distribution), in trabecular cube with embedded hexagonal
      structure, as compared to VP and KP. This is comparable to the results of the
      experimental study already performed; it was shown that the improvement of
      mechanical behavior of the vertebra was observed as: 83% increase in the range of
      displacements before getting to the ultimate strength (increasing the toughness)
      after setting hexagonal pearls inside vertebrae. Both the material and geometry
      of implant influenced the amount of Von Mises stress in the structure.
      CONCLUSION: The new proposed method can be offered as a substitute for the KP.
      The implant geometry had a more obvious effect on the amount of Von Mises stress,
      as compared to the implant material.

PMID- 29184756
TI  - Balance control during gait initiation: State-of-the-art and research
      perspectives.
AB  - It is well known that balance control is affected by aging, neurological and
      orthopedic conditions. Poor balance control during gait and postural maintenance
      are associated with disability, falls and increased mortality. Gait initiation -
      the transient period between the quiet standing posture and steady state walking 
      is a functional task that is classically used in the literature to investigate
      how the central nervous system (CNS) controls balance during a whole-body
      movement involving change in the base of support dimensions and center of mass
      progression. Understanding how the CNS in able-bodied subjects exerts this
      control during such a challenging task is a pre-requisite to identifying motor
      disorders in populations with specific impairments of the postural system. It may
      also provide clinicians with objective measures to assess the efficiency of
      rehabilitation programs and better target interventions according to individual
      impairments. The present review thus proposes a state-of-the-art analysis on: (1)
      the balance control mechanisms in play during gait initiation in able bodied
      subjects and in the case of some frail populations; and (2) the biomechanical
      parameters used in the literature to quantify dynamic stability during gait
      initiation. Balance control mechanisms reviewed in this article included
      anticipatory postural adjustments, stance leg stiffness, foot placement, lateral
      ankle strategy, swing foot strike pattern and vertical center of mass braking.
      Based on this review, the following viewpoints were put forward: (1) dynamic
      stability during gait initiation may share a principle of homeostatic regulation
      similar to most physiological variables, where separate mechanisms need to be
      coordinated to ensure stabilization of vital variables, and consequently; and (2)
      rehabilitation interventions which focus on separate or isolated components of
      posture, balance, or gait may limit the effectiveness of current clinical
      practices.

PMID- 29184758
TI  - Atlantoaxial rotatory displacement in children.
AB  - AIM: To correlate the Pang and Lee class with the clinical course in a
      consecutive series of patients presenting with painful torticollis. METHODS:
      Forty-seven dynamic rotational computed tomography (CT) scans in 35 patients were
      classified into one of the five types defined by Pang and Li, including types I
      (atlantoaxial rotatopry fixation), II ("pathologic stickiness" without crossover
      of C1 on C2), III ("pathologic stickiness" with crossover of C1 on C2), IV
      (normal or muscular torticollis), and V (diagnostic grey zone). The Pang and Li
      class was then compared with the radiologist's report, which was graded abnormal,
      diagnosis of rotatory subluxation or fixation, or non-diagnostic. Medical records
      were reviewed and the clinical course was compared among the five sub-types.
      RESULTS: We reviewed 47 CT scans in 35 patients, and the majority were performed
      without sedation. The average age was 7.7 years (4-14 years old) and associated
      conditions included minor trauma (20%), surgical procedures around the head and
      neck (29%), and Grisels syndrome (20%). Twenty-six percent of our studies fell
      within the pathologic spectrum (5% type 1 or rotatory fixation, 21% types 2 and 3
      or rotatory subluxation), while 45% were classified as muscular torticollis (45%)
      and 28% fell within the diagnostic grey zone. Seven radiologists interpreted
      these studies, and their interpretation was discordant in 45% of cases. Clinical
      resolution occurred in 27 of 29 cases for which follow-up was available. One of
      two patients with fixed rotatory subluxation required a C1-C2 arthrodesis.
      CONCLUSION: The Pang and Li classification characterizes a spectrum of
      abnormalities in rotation to facilitate communication, although the indications
      for dynamic CT scan should be further defined.

PMID- 29184759
TI  - Hypothenar fat pad flap vs conventional open release in primary carpal tunnel
      syndrome: A randomized controlled trial.
AB  - AIM: To compared outcomes between the hypothenar fat pad flap (HTFPF) and
      conventional open carpal tunnel release (COR) in primary carpal tunnel syndrome
      (CTS). METHODS: Forty-five patients (49 hands) were enrolled into the study from
      January 2014 to March 2016, 8 patients were excluded. Randomization was conducted
      in 37 patients (41 hands) by computer generated (Block of four randomization)
      into COR and HTFPF group. Nerve conduction study (NCS) included distal sensory
      latency (DSL), distal motor latency (DML), sensory amplitude (S-amp), motor
      amplitude (M-amp) and sensory nerve conduction velocity (SCV) were examined at 6
      and 12 wk after CTR. Levine score, grip and pinch strength, pain [visual analog
      scale (VAS)], 2-point discrimination (2-PD), Semmes-Weinstein monofilament test
      (SWM), Phalen test and Tinel's sign were evaluated in order to compare treatment
      outcomes. RESULTS: The COR group, 19 patients (20 hands) mean age 50.4 years. The
      HTFPF group, 20 patients (21 hands) mean age 53.3 years. Finally 33 patients (36
      hands) were analysed, 5 patients were loss follow-up, 17 hands in COR and 19
      hands in HTFPF group. NCS revealed significant difference of DSL in HTFPF group
      at 6 wk (P < 0.05) compared with the COR group. S-amp was significant improved
      postoperatively in both groups (P < 0.05) but not significant difference between
      two groups. No significant difference of DML, M-amp and SCV postoperatively in
      both groups and between two groups. Levine score, pain (VAS), grip and pinch
      strength, 2-PD, SWM, Phalen test and Tinel's sign were improved postoperatively
      in both groups, but there was no significant difference between two groups.
      CONCLUSION: There is no advantage outcome in primary CTS for having additional
      HTFPF procedure in CTR. COR is still the standard treatment. Nevertheless,
      improvement of DSL and S-amp could be observed at 6 wk postoperatively.

PMID- 29184760
TI  - Rhabdomyolysis with different etiologies in childhood.
AB  - AIM: To investigate different etiologies and management of the rhabdomyolysis in
      children. METHODS: Eight pediatric rhabdomyolysis cases who applied to the Dokuz
      Eylul University Faculty of Medicine Department of Pediatric Nephrology with
      different etiologies between January 2004 and January 2012 were evaluated in
      terms of age, gender, admission symptoms, physical examination findings, factors
      provoking rhabdomyolysis, number of rhabdomyolysis attacks, laboratory results,
      family history and the final diagnosis received after the treatment. RESULTS:
      Average diagnosis ages of eight cases were 129 (24-192) +/- 75.5 mo and five of
      them were girls. All of them had applied with the complaint of muscle pain, calf
      pain, and dark color urination. Infection (pneumonia) and excessive physical
      activity were the most important provocative factors and excessive licorice
      consumption was observed in one case. In 5 cases, acute kidney injury was
      determined and two cases needed hemodialysis. As a result of the further
      examinations; the cases had received diagnoses of rhabdomyolysis associated with
      mycoplasma pneumoniae, sepsis associated rhabdomyolysis, licorice-induced
      hypokalemic rhabdomyolysis, carnitine palmitoyltransferase II deficiency, very
      long-chain acyl-CoA dehydrogenase deficiency, congenital muscular dystrophy and
      idiopathic paroxysmal rhabdomyolysis (Meyer-Betz syndrome). CONCLUSION: It is
      important to distinguish the sporadic and recurrent rhabdomyolysis cases from
      each other. Recurrent rhabdomyolysis cases should follow up more regardful and
      attentive.

PMID- 29184761
TI  - Estimating extraction fraction and blood flow by combining first-pass myocardial
      perfusion and T1 mapping results.
AB  - Background: Quantifying myocardial perfusion is complicated by the complexity of
      pharmacokinetic model being used and the reliability of perfusion parameter
      estimates. More complex modeling provides more information about the underlying
      physiology, but too many parameters in complex models introduce a new problem of
      reliable estimation. To overcome the problem of multiple parameters, we have
      developed a technique that combines knowledge from two different cardiac magnetic
      resonance (MR) imaging techniques: dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) and T1 mapping. Using extracellular volume (ECV) estimates from
      T1 mapping may allow more robust model parameter estimates. Methods: Simulations
      and human scans were performed. The myocardial perfusion scans used an ungated
      saturation recovery prepared TurboFLASH pulse sequence. Four short-axis (SA)
      slices were acquired after a single saturation pulse with a saturation recovery
      time of ~25 ms before the first slice. Gadoteridol was injected and ~240 frames
      were acquired over a minute with shallow breathing and no electrocardiograph
      (ECG) gating. This was followed 20+/-5 minutes later by an injection of
      regadenoson to induce hyperemia. The data were acquired using an under-sampled
      golden angle radial acquisition. Modified look-locker inversion recovery (MOLLI)
      T1 mapping was performed in 3 slices pre- and post-contrast. The pre- and post
      contrast T1 maps were used for ECV estimation. Quantification of perfusion was
      done using a 4-parameter model with additional information about ECV supplied
      during model fitting. Phase contrast scans of the coronary sinus (CS) were
      acquired at rest and immediately after the stress perfusion acquisition to
      estimate global flow. Results: Without ECV information, the 5-parameter model
      fails to converge to a unique solution and often gives incorrect estimates for
      the perfusion parameters. The myocardial blood flow (MBF) estimates during rest
      and stress were 0.9+/-0.1 and 2.3+/-0.6 mL/min/g, respectively. The extraction
      fraction estimates were 0.49+/-0.04 and 0.34+/-0.05 during rest and stress,
      respectively. Conclusions: These results show that it is possible to successfully
      fit a dynamic perfusion model with an extraction fraction parameter by using
      information from T1 mapping scans. This hybrid approach is especially important
      when the 5-parameter model alone fails to converge on a unique solution. This
      work is a good example of exploiting information overlaps between various cardiac
      MR imaging techniques.

PMID- 29184762
TI  - TumourMetrics: a comprehensive clinical solution for the standardization of DCE
      MRI analysis in research and routine use.
AB  - Background: A reliable analysis methodology is needed to provide valuable imaging
      biomarkers for clinical trials, with particular regards to dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) application using pharmacokinetic
      (PK) model analysis. In order to address this scientific challenge, we provided a
      comprehensive analysis solution that could overcome the impediments to clinical
      research and routine use. Methods: TumourMetrics has been designed to meet the
      Quantitative Imaging Biomarkers Alliance (QIBA) v.1.0 profile. The quality
      performance was assessed using the QIBA test data and our customizable numeric
      phantom. The analysis workflow is made customizable to facilitate standardization
      of optimized protocol across centers. Results: Our quantification workflow
      estimated the PK model parameters accurately. The method is robust, almost fully
      automatic and allows a direct integration of the results into the diagnostic
      workflow. Conclusions: The analysis is easy-to-use and accessible for routine
      implementation of DCE-MRI into clinical practice.

PMID- 29184763
TI  - Usefulness of enhancement-perfusion mismatch in differentiation of CNS lymphomas
      from other enhancing malignant tumors of the brain.
AB  - Background: Surgical planning and treatment options for primary or secondary
      central nervous system lymphomas (PCNSL or SCNSL) are different from other
      enhancing malignant lesions such as glioblastoma multiforme (GBM), anaplastic
      gliomas and metastases; so, it is critical to distinguish them preoperatively. We
      hypothesized that enhancement-perfusion (E-P) mismatch on dynamic susceptibility
      weighted magnetic resonance (DSC-MR) perfusion imaging which corresponds to low
      mean relative cerebral blood volume (mean rCBV) in an enhancing portion of the
      tumor should allow differentiation of CNS lymphomas from other enhancing
      malignant lesions. Methods: We retrospectively reviewed pre-treatment MRI exams,
      including DSC-MR perfusion images of 15 lymphoma patients. As a control group,
      pre-treatment DSC-MR perfusion images of biopsy proven 18 GBMs (group II), 13
      metastases (group III), and 10 anaplastic enhancing gliomas (group IV) patients
      were also reviewed. Region of interests (ROIs) were placed around the most
      enhancing part of tumor on contrast-enhanced T1WI axial images and images were
      transferred onto co-registered DSC perfusion maps to obtain CBV in all 4 groups.
      The mean and maximum relative CBV values were obtained. Statistical analysis was
      performed on SPSS software and significance of the results between the groups was
      done with Mann-Whitney test, whereas optimal thresholds for tumor differentiation
      were done by receiver operating characteristic (ROC) analysis. Results: The
      enhancing component of CNS lymphomas were found to have significantly lower mean
      rCBV compared to enhancing component of GBM (1.2 versus 4.3; P<0.001), metastasis
      (1.2 versus 2.7; P<0.001), and anaplastic enhancing gliomas (1.2 versus 2.4;
      P<0.001). Maximum rCBV of enhancing component of lymphoma were significantly
      lower than GBM (3.1 versus 6.5; P<0.001) and metastasis (3.1 versus 4.9;
      P<0.013), and not significantly lower than anaplastic enhancing gliomas (3.9
      versus 4.2; P<0.08). On the basis of ROC analysis, mean rCBV provided the best
      threshold [area under the curve (AUC) =0.92] and had better accuracy in
      differentiating malignant lesions. Conclusions: E-P mismatch in DSC perfusion MR,
      i.e., low mean rCBV in an enhancing portion of the tumor is strongly suggestive
      of lymphoma and should allow differentiation of CNS lymphoma from other enhancing
      malignant lesions.

PMID- 29184764
TI  - Dual energy CT angiography in peripheral arterial stents: optimal scanning
      protocols with regard to image quality and radiation dose.
AB  - Background: To determine the optimal scanning protocols of dual energy computed
      tomography angiography (DECTA) in terms of radiation dose and image quality
      assessment at different keV levels, and compare it with conventional computed
      tomography angiography (CTA) in patients treated with peripheral arterial stents.
      Methods: Twenty-nine patients with previous stent placement in peripheral
      arteries were evaluated with DECTA. Images were reconstructed with virtual
      monochromatic spectral imaging (VMS) at 65, 68, 70 and 72 keV and adaptive
      statistical iterative reconstruction (ASIR) at 50% compared with CTA. Image
      quality comprising image noise, signal-to-noise ratio (SNR) and contrast-to-noise
      ratio (CNR) were assessed, and radiation dose was compared. Effects of different
      type of peripheral arterial stents on image quality were also evaluated. Fifty
      six uniquely identified stents that were located in common iliac arteries (CIA),
      external iliac arteries (EIA) and superficial femoral arteries (SFA) were
      evaluated. Results: Within subjects, the results showed that DECTA images (VMS)
      had less noise than the CTA images for CIA, EIA and SFA stents, with the lowest
      noise at 72 keV. Also, the VMS images had greater SNR than the CTA images for the
      EIA stents (P<0.05); and the VMS images had greater CNR than the CTA images for
      CIA, EIA, and SFA stents (P<0.001). Also, on CT attenuation, VMS continued to
      outperform CTA, but to a lesser extent. Between subjects, average VMS noise
      varied significantly with the type of the stent used (P=0.025) for CIA stents.
      Radiation dose was highly significant between DECTA and conventional CTA scans
      (6.98 vs. 7.40 mSv, P=0.047). Conclusions: We conclude that an optimal scanning
      protocol consisting of 72 keV and 50% ASIR leads to better image quality for
      DECTA in peripheral arterial stenting when compared to conventional CTA.

PMID- 29184765
TI  - The novel targets of DL-3-n-butylphthalide predicted by similarity ensemble
      approach in combination with molecular docking study.
AB  - Background: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic
      stroke, and may play a neuroprotective role by acting on multiple active targets.
      The aim of this study was to predict the target proteins of NBP in mammalian
      cells. Methods: The similarity ensemble approach search tool (SEArch), one of the
      commonly used public bioinformatics tools for target prediction, was employed in
      the experiment. The molecular docking of NBP to target proteins was performed by
      using the three-dimensional (3-D) crystal structure, substrate free. The software
      AutoDock Vina was used for all dockings. The binding targets of NBP were
      illustrated as 3-D and 2-D diagrams. Results: Firstly, the results showed that
      NBP bounded to the same binding site on NAD(P)H quinone oxidoreductases (NQO1) as
      the substrate FAD, leading to competitive inhibition for the catalytic site with 
      7.2 kcal/mol. This might break the 3-D structure of NQO1 and bring about P53
      degradation, resulting in a decrease of p53-mediated apoptosis in ischemic brain
      cells. Secondly, NBP might exert its therapeutic effect on acute ischemic stroke
      via modulating indoleamine 2,3-dioxygenase (IDO) bioactivity after associating
      with it. NBP could alleviate the depression following ischemic stroke by
      inhibiting IDO. Thirdly, NBP might modulate the function of NADH-ubiquinone
      oxidoreductase by competitively embedding itself into this complex, further
      affecting mitochondrial respiration in cerebrovascular diseases as an anti
      oxidant agent. Conclusions: Three potential target proteins of NBP were
      identified, which may provide a novel aspect for better understanding the
      protective effects of NBP on the nervous system at the molecular level.

PMID- 29184767
TI  - Preliminary results of vibro-acoustography evaluation of bone surface and bone
      fracture.
AB  - Background: Vibro-acoustography (VA) uses two co-focused ultrasound beams with
      slightly different frequencies. The beams interact and generate a low-frequency
      focus to excite an object. Methods: A two-element confocal ultrasound transducer
      with central frequency at 3.2 MHz was used to generate the low-frequency
      excitation (30 kHz) and the response of the bone to that excitation was acquired
      by a dedicated hydrophone. The face of the confocal transducer was positioned
      parallel to the surface of the bone at a focal length of 7 cm. The hydrophone was
      fixed to the side of the transducer, out of the path of the ultrasonic beam.
      Results: The resulting image clearly showed the bone fracture with resolution of
      0.25 mm and high contrast with well-defined borders. Conclusions: In this paper,
      we present preliminary results of VA imaging of bone surface and of bone fracture
      using an experimental set-up. Our results encourage future studies using VA to
      evaluate bone fractures.

PMID- 29184766
TI  - An investigation of correlation between left coronary bifurcation angle and
      hemodynamic changes in coronary stenosis by coronary computed tomography
      angiography-derived computational fluid dynamics.
AB  - Background: To investigate the correlation between left coronary bifurcation
      angle and coronary stenosis as assessed by coronary computed tomography
      angiography (CCTA)-generated computational fluid dynamics (CFD) analysis when
      compared to the CCTA analysis of coronary lumen stenosis and plaque lesion length
      with invasive coronary angiography (ICA) as the reference method. Methods: Thirty
      patients (22 males, mean age: 59+/-6.9 years) with calcified plaques at the left
      coronary artery were included in the study with all patients undergoing CCTA and
      ICA examinations. CFD simulation was performed to analyze hemodynamic changes to
      the left coronary artery models in terms of wall shear stress, wall pressure and
      flow velocity, with findings correlated to the coronary stenosis and degree of
      bifurcation angle. Calcified plaque length was measured in the left coronary
      artery with diagnostic value compared to that from coronary lumen and bifurcation
      angle assessments. Results: Of 26 significant stenosis at left anterior
      descending (LAD) and 13 at left circumflex (LCx) on CCTA, only 14 and 5 of them
      were confirmed to be >50% stenosis at LAD and LCx respectively on ICA, resulting
      in sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV) of 100%, 52%, 49% and 100%. The mean plaque length was
      measured 5.3+/-3.6 and 4.4+/-1.9 mm at LAD and LCx, respectively, with diagnostic
      sensitivity, specificity, PPV and NPV being 92.8%, 46.7%, 61.9% and 87.5% for
      extensively calcified plaques. The mean bifurcation angle was measured 83.9+/
      13.6o and 83.8+/-13.3o on CCTA and ICA, respectively, with no significant
      difference (P=0.98). The corresponding sensitivity, specificity, PPV and NPV were
      100%, 78.6%, 84.2% and 100% based on bifurcation angle measurement on CCTA, 100%,
      73.3%, 78.9% and 100% based on bifurcation angle measurements on ICA,
      respectively. Wall shear stress was noted to increase in the LAD and LCx models
      with significant stenosis and wider angulation (>80o), but demonstrated little or
      no change in most of the coronary models with no significant stenosis and
      narrower angulation (<80o). Conclusions: This study further clarifies the
      relationship between left coronary bifurcation angle and significant stenosis,
      with angulation measurement serving as a more accurate approach than coronary
      lumen assessment or plaque lesion length for determining significant coronary
      stenosis. Left coronary bifurcation angle is suggested to be incorporated into
      coronary artery disease (CAD) assessment when diagnosing significant CAD.

PMID- 29184768
TI  - Identifying osteoporotic vertebral endplate and cortex fractures.
AB  - Osteoporosis is the most common metabolic bone disease, and vertebral fractures
      (VFs) are the most common osteoporotic fracture. A single atraumatic VF may lead
      to the diagnosis of osteoporosis. Prevalent VFs increase the risk of future
      vertebral and non-vertebral osteoporotic fracture independent of bone mineral
      density (BMD). The accurate and clear reporting of VF is essential to ensure
      patients with osteoporosis receive appropriate treatment. Radiologist has a vital
      role in the diagnosis of this disease. Several morphometrical and radiological
      methods for detecting osteoporotic VF have been proposed, but there is no
      consensus regarding the definition of osteoporotic VF. A vertebra may fracture
      yet not ever result in measurable changes in radiographic height or area. To
      overcome these difficulties, algorithm-based qualitative approach (ABQ) was
      developed with a focus on the identification of change in the vertebral endplate.
      Evidence of endplate fracture (rather than variation in vertebral shape) is the
      primary indicator of osteoporotic fracture according to ABQ criteria. Other
      changes that may mimic osteoporotic fractures should be systemically excluded. It
      is also possible that vertebral cortex fracture may not initially occur in
      endplate. Particularly, vertebral cortex fracture can occur in anterior vertebral
      cortex without gross vertebral deformity (VD), or fractures deform the anterior
      vertebral cortex without endplate disruption. This article aims to serve as a
      teaching material for physicians or researchers to identify vertebral
      endplate/cortex fracture (ECF). Emphasis is particularly dedicated to identifying
      ECF which may not be associated apparent vertebral body collapse. We believe a
      combined approach based on standardized radiologic evaluation by experts and
      morphometry measurement is the most appropriate approach to detect and classify
      VFs.

PMID- 29184769
TI  - Diffuse glioblastoma resembling acute hemorrhagic leukoencephalitis.
AB  - We report the case of a young man with sudden onset of diplopia after an upper
      respiratory tract infection. Based on the first radiological findings acute
      hemorrhagic leukoencephalitis, a variant of acute disseminated encephalomyelitis,
      was suspected and treatment with high dose intravenous dexamethasone was started
      but it was stopped for intolerance. The patient clinically worsened, developing
      gait instability, ataxia and ophthalmoplegia; brain MRI performed 20 days later
      showed severe progression of the disease with subependymal dissemination. After
      brain biopsy of the right temporal lesion the histological diagnosis was
      glioblastoma. These findings suggest that MRI features of acute hemorrhagic
      leukoencephalitis may dissimulate the diagnosis of diffuse glioma/glioblastoma.
      This case underscores the importance of considering diffuse glioma in the
      differential diagnosis of atypical signs and symptoms of acute hemorrhagic
      leukoencephalitis and underlines the relevant role of integrating neuroradiologic
      findings with neuropathology.

PMID- 29184770
TI  - Dentinogenic ghost cell tumor-a rare case report with review of literature.
AB  - Dentinogenic ghost cell tumors (DGCT) are very rare tumors considered as solid
      variants of calcifying epithelial odontogenic cysts (CEOC). They are locally
      invasive neoplasms and their main characteristic features are ameloblastoma like
      odontogenic epithelial proliferation, an aberrant keratinization in the form of
      ghost cells and dysplastic dentin. DGCT occur as two forms intraosseous (central)
      and extra osseous (peripheral), of which more aggressive intraosseous variety
      requires careful monitoring and aggressive local resection to prevent recurrence.
      This paper discusses a case of a 14-year-old male patient with a complaint of
      swelling in his right mandibular premolar molar region since 4 months and missing
      permanent right mandibular canine and first premolar was also observed. The
      lesion was diagnosed with radiological, cytological and histopathological
      investigations which revealed it to be rarest entity.

PMID- 29184771
TI  - Acute myocardial infarction and stroke secondary to valve thrombosis following
      transcatheter aortic valve replacement-what can happen when antiplatelet agents
      are stopped.

PMID- 29184772
TI  - How liver pathologies contribute to T1rho contrast require more careful studies.

PMID- 29184773
TI  - Management of penile cancer.

PMID- 29184774
TI  - Updates on the epidemiology and risk factors for penile cancer.
AB  - Penile cancer is a rare neoplasm representing less than 1% of all malignancies in
      the USA and Europe but is a significant public health hazard in the developing
      world. Male neonatal circumcision has been associated with a dramatic decrease in
      penile cancer rates with countries such as Israel, where circumcision is widely
      performed, having the lowest incidence in the world at <0.1% of malignancies.
      Many risk factors have been identified for penile cancer including phimosis, lack
      of circumcision, obesity, lichen sclerosis, chronic inflammation, smoking, UVA
      phototherapy, socioeconomic status, human papillomavirus (HPV) infection and
      immune compromised states. The relationship between these factors and invasive
      disease varies and continues to be investigated. Our objective was to present a
      contemporary overview of the epidemiology and risk factors for invasive penile
      cancer.

PMID- 29184776
TI  - Topical Therapy for non-invasive penile cancer (Tis)-updated results and
      toxicity.
AB  - Penile cancer is a rare malignancy estimated to affect 26,000 men globally each
      year. The association with penile cancer, in particular non-invasive disease, and
      human papilloma virus (HPV) is well known. Ninety-five percent of cases of penile
      cancer are squamous cell carcinoma (SCC), which are staged using the TNM staging
      system. Terminology describing the histological appearance of non-invasive penile
      cancer has changed with all cases grouped under the umbrella term of penile
      intraepithelial neoplasia (PeIN); either undifferentiated or differentiated. This
      replaces previous terms such as carcinoma in situ (CIS) and eponymous names such
      as Bowen's disease. This change is recognised by the World Health Organisation
      (WHO). The topical treatments most commonly used for PeIN are 5-fluorouracil (5
      FU) and imiquimod (IQ). Other treatments such as photodynamic therapy (PDT) are
      used but to a lesser degree. The evidence for all of these treatments is
      heterogenous with no randomised data available. Overall up to 57% complete
      response has been reported with a low number of serious adverse events. In this
      article, we aim to review the available evidence for the topical treatment of non
      invasive penile cancer specifically regarding its efficacy and toxicity.

PMID- 29184775
TI  - Relationship between human papillomavirus and penile cancer-implications for
      prevention and treatment.
AB  - Penile cancer is a rare disease in the United States, but rates are increasing,
      causing concern. Several risk factors have been associated with the disease,
      including human papillomavirus (HPV) infection. Knowledge of HPV pathogenesis has
      led to the development of a vaccine, which has proven instrumental in reducing
      the incidence of female HPV-related cancers, but results in men have yet to be
      elucidated. Fortunately, rates of vaccination are up-trending in both males and
      females in the past several years. In addition, targeted therapies are the focus
      of several ongoing research efforts. Some of these therapeutics are currently in
      use, while several are in trials. With continued patient education and research,
      both treatment and prevention of HPV-related pre-malignant lesions and penile
      cancer will likely diminish.

PMID- 29184778
TI  - Technical considerations to minimize complications of inguinal lymph node
      dissection.
AB  - Penile cancer is a rare malignancy with a high propensity for regional
      dissemination. Current guidelines recommend inguinal lymphadenectomy in patients
      with penile cancer for palpable inguinal lymph nodes or in certain cases of
      nonpalpable inguinal lymph nodes. For many years, this procedure was performed
      with a traditional open approach and carried significant morbidity due to severe
      lymphedema, flap necrosis, wound infections, and seroma formation. The evolution
      of inguinal lymphadenectomy surgery for patients with penile cancer to a more
      minimally invasive approach has greatly reduced the morbidity of the procedure.
      Complications of inguinal lymphadenectomy can be minimized with modifications in
      surgical approach with the use of endoscopic, robotic, and various reconstructive
      methods. This review focuses on various intraoperative techniques to reduce
      morbidity in inguinal lymphadenectomies for penile cancer.

PMID- 29184777
TI  - Penile sparing surgical approaches for primary penile tumors: preserving function
      and appearance.
AB  - Penile cancer is a rare and potentially disfiguring disease. There are multiple
      treatment options for primary penile lesions. Penile sparing approaches offer an
      attractive option as they can provide several quality of life benefits without
      detrimental oncologic outcomes. With appropriate diagnostic evaluation and
      staging, penile sparing techniques provide proper cancer control with improved
      cosmetic and functional results. Regardless of the chosen treatment modality, a
      commitment to close follow-up remains a critical component of all treatment
      considerations. The goal of this review is to provide an overview of the multiple
      treatment strategies for primary penile tumors with a focus on penile sparing
      surgical approaches.

PMID- 29184779
TI  - Robotic inguinal lymphadenectomy for penile cancer: the why, how, and what.
AB  - Squamous cell carcinoma of the penis (SCC-P) demonstrates a reliable pattern of
      spread to the lymph nodes of the groin. High grade and higher stage (pT1b or
      greater) SCC-P demonstrate a higher propensity for metastasis to the inguinal
      lymph nodes. Further, lymphadenopathy progresses in a predictable fashion, from
      superficial inguinal lymph nodes to deep inguinal lymph nodes to pelvic lymph
      nodes, with limited survival noted for those patients with progression to pelvic
      lymph nodes. Fortunately, inguinal lymphadenectomy can provide cure and
      improvement in RFS for SCC-P. Unfortunately open inguinal lymphadenectomy is
      associated with significant morbidity. Perhaps owing to this morbidity, inguinal
      lymphadenectomy is underperformed in the US. In other words, urologists only
      offer inguinal lymphadenectomy for high risk SCC-P in only a minority of cases
      and even when performed, lymph node yield is often unsatisfactory (less than 8
      nodes per groin). Recently, a laparoendoscopic inguinal lymphadenectomy has been
      developed as a new approach to offer potentially curative lymph node resection
      while minimizing morbidity. The robotic platform has since been adapted for this
      approach and several reports demonstrate significant improvements in morbidity
      while maintaining oncologic equivalency. This review highlights the rationale for
      inguinal lymphadenectomy, inguinal lymph node anatomy, and technical
      considerations and outcomes of laparoscopic and robotic inguinal lymphadenectomy.

PMID- 29184780
TI  - The role of PET/CT imaging in penile cancer.
AB  - Positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG)
      combined with computed tomography (CT) provides functional imaging combined with
      anatomic information, improving diagnostic accuracy and confidence. Although
      virtually all primary penile tumors are FDG-avid, PET/CT is not recommended for
      primary tumor staging as it has limited spatial resolution and is hampered by
      urinary FDG excretion. The accuracy of PET/CT for lymph node staging seems to
      improve with the pretest likelihood of metastatic nodes. In groins with normal
      physical examination, sensitivity is only 57%. In groins with palpably enlarged
      lymph nodes, sensitivity of PET/CT reaches 96%. For pelvic lymph nodes and
      distant metastases, PET/CT is more accurate if inguinal metastases are present.
      However, these results are based on a very limited number of studies. Overall,
      the role of PET/CT imaging in penile cancer remains ambiguous, especially in
      inguinal lymph nodes. During staging and follow-up, it may be particularly useful
      in detecting pelvic lymph node metastases and occult distant metastases prior to
      systemic chemotherapy and/or extensive surgery, improving selection of patients
      that are most likely to benefit from such therapies.

PMID- 29184781
TI  - Clinical scenarios for neoadjuvant chemotherapy of squamous penile cancer that is
      clinically node positive.
AB  - Squamous penile cancer may be localized to the phallus, metastatic to regional
      lymph nodes, or metastatic to distant lymph nodes or other organs. In the
      clinical situation of regional lymph node metastasis, a multimodality approach
      can have a big impact on outcomes. In particular, use of systemic chemotherapy as
      a neoadjuvant treatment is discussed, with several examples illustrating
      instances of regression and of resistance, and contrasting with adjuvant timing
      for use of chemotherapy. Radiation with coordinated combined chemotherapy is
      another complementary, locally directed approach that can be considered for men
      with squamous penile cancer with regional lymph node spread. The randomized trial
      InPACT (International Penile Cancer Adjuvant Chemotherapy Trial, NCT02305654)
      will enroll some of the squamous penile cancer patients with clinically node
      positive disease.

PMID- 29184782
TI  - Beyond chemotherapy for advanced disease-the role of EGFR and PD-1 inhibitors.
AB  - Penile squamous cell carcinoma (SCC) is a rare malignancy with limited treatment
      options when the tumor is unresectable and/or chemorefractory. Triplet systemic
      chemotherapy regimens including taxane and cisplatin are recommended, but the
      response duration can be short and the treatment-related toxicity high. Only a
      small proportion of patients survive 1 year or longer with the current standard
      treatment paradigm. Beyond chemotherapy, the use of novel targeted agents, either
      alone or in combination with traditional chemotherapeutic agents, has appeared to
      have promising efficacy in patients with platinum-refractory penile cancer. The
      frequent overexpression of PD-L1 in advanced penile SCC indicates the potential
      efficacy of PD-1 inhibitors. Upcoming clinical trials using the immune check
      point inhibitors may provide exciting landscape and change the paradigm for
      patients in the future.

PMID- 29184783
TI  - Contemporary role of radiotherapy in the management of penile cancer.
AB  - Penile cancer is a rare clinical entity that contributes to significant patient
      morbidity and mortality. Human papilloma virus (HPV) plays an important role in
      the carcinogenesis of penile squamous cell carcinoma (SCC), is associated with
      improved clinical outcomes, and is predictive for response to treatment with
      chemotherapy and radiotherapy. Historically, treatment consisted of radical
      surgery with partial or total penectomy. While effective for local control,
      surgical resection can impart significant physical, psychological and sexual
      dysfunction for afflicted men. Organ preservation strategies offer significant
      quality of life advantages over standard surgery and can be utilized without
      compromising oncological control. As an alternative or adjunct to surgical
      resection, radiation therapy can be used for organ preservation strategies
      successfully in up to 70% of patients. A variety of treatment techniques can be
      employed depending on the location and burden of disease. Limited disease can be
      amenable to treatment with interstitial brachytherapy, surface mold plesiotherapy
      or external beam radiotherapy. For locally advanced presentations, or for
      patients not amenable to surgical resection, excellent clinical outcomes can be
      achieved using a combination of chemotherapy and radiation therapy. Here, we
      discuss the management of penile SCC using modern radiation therapy treatment
      techniques, the expected clinical outcomes for organ preservation, as well as the
      management of side-effects and toxicities. While large randomized trials are
      being developed, the management of penile cancer is informed from the management
      of other of other anogenital malignancies, which we also review.

PMID- 29184784
TI  - Surveillance strategies in the management of penile cancer.
AB  - Penile cancer is a rare disease and can be associated with a high risk of
      recurrence in regional lymph nodes and distant sites. Surveillance strategies
      geared towards early detection and treatment are recommended given the
      significant morbidity and mortality associated with recurrences. Although
      physical examination is the single most important surveillance strategy, imaging
      is an important adjunct in high-risk disease and certain clinical scenarios.

PMID- 29184785
TI  - Psychosocial impact of penile carcinoma.
AB  - Penile carcinoma is a rare malignancy with a potential for local invasion and
      regional/distant extension. Penile cancer can be cured in over 80% of cases if
      diagnosed early. However, local treatment, although potentially lifesaving, can
      be mutilating and devastating for the patient's psychological well-being. In
      patients with long-term survival after penile cancer, sexual dysfunction, voiding
      problems and cosmetic penile appearance may adversely affect the patient's
      quality of life. Although there is little data in the literature about
      psychosocial impact of penile carcinoma, organ-preserving treatment seems to
      allow for better quality of life and sexual function and should be offered to all
      patients whenever feasible.

PMID- 29184786
TI  - Phosphodiesterase type 5 inhibitors usage and prostate cancer: a match-paired
      analysis.
AB  - Background: To treat erectile dysfunction (ED), phosphodiesterase type 5
      inhibitors (PDE5i) are commonly used. However, to date, only a few studies exist
      evaluate a possible effect on the incidence of prostate cancer. One such study
      completed by the authors' institution suggested men who use PDE5i for ED may have
      a lower incidence of prostate cancer. This study was meant to address some of the
      shortcomings of the former study and further characterize the link between
      prostate cancer and PDE5i use. Methods: A retrospective, match-paired analysis
      was undertaken: 5,717 patients were identified between 2000 and 2011; a 1:2 match
      pair analysis ultimately identified 394 cases with cancer and 788 controls
      without cancer. Pairs were matched based on age, ethnicity, and PSA value.
      Results: No correlation existed between PDE5i use and prostate cancer [OR 1.02,
      95% confidence interval (CI): 0.78-1.35, P=0.8842] or diabetes mellitus and
      prostate cancer (OR 1.12, 95% CI: 0.84-1.48, P=0.4499). A statistically
      significant correlation was demonstrated with PSA and prostate cancer (OR 1.48,
      95% CI: 1.38-1.58, P<0.0001). Conclusions: The data suggest that there is
      essentially no association with PDE5i use and prostate cancer.

PMID- 29184787
TI  - Correlation of self-reported urologic symptoms with systemic health conditions in
      minority men.
AB  - Background: To investigate the correlation between presence and severity of
      urologic symptoms and self-reported systemic health conditions in minority men.
      Methods: Questionnaires were distributed at a Men's Minority Health Fair.
      Urologic symptoms were assessed with the International Prostate Symptom Score
      (IPSS), Sexual Health Inventory for Men (SHIM) and NIH Chronic Prostatitis
      Symptom Score (CPSI). Each was graded as absent/mild [0], moderate [1] or severe
      [2] by standard criteria for each and totaled for a urologic score (US). Other
      questions included age, height/weight and queried heart disease, diabetes,
      anxiety/stress, sleep apnea and neurologic disease. A systemic score (SS) graded
      each plus obesity for 6 domains (0-2 for each). Results: A total of 52 men
      completed the surveys with a mean age of 58.8 (range, 37-76) years. By symptom
      score criteria, 17 (33%) had 1 urologic condition, 19 (37%) had 2 and 5 (10%) had
      all 3. Mean total US was 1.9 (range, 0-6) and mean SS was 2.9 (range, 0-10).
      There was a strong correlation between US and SS (Spearman Rho =0.73, P<0.0001).
      The hierarchy of systemic condition impact on US was cardiovascular > anxiety >
      obesity > diabetes > sleep apnea > neurologic. By multivariable analysis, after
      adjusting for age, each systemic component strongly correlated with the US. The
      multivariable model with age plus all of the systemic scores predicted US more
      accurately than with any one of its components alone. Conclusions: Self-reported
      systemic health conditions correlate strongly with presence and severity of
      urologic symptoms in minority men.

PMID- 29184788
TI  - Racial variations in response to intralesional collagenase clostridium
      histolyticum in men with Peyronie's disease.
AB  - Background: An examination of potential racial variations between Caucasian
      American (CA) and African American (AA) men in the efficacy and safety of
      collagenase clostridium histolyticum (CCH) in the treatment of Peyronie's disease
      (PD). Methods: We retrospectively reviewed the records for all patients treated
      with CCH for PD between 04/2014 and 05/2017. Patients were divided into two
      groups based on their self-reported race. The primary outcomes of interest were
      final change in curvature after CCH treatment regardless of number of CCH cycles
      received, and frequency of treatment-related adverse events (TRAEs). Results: A
      total of 159 patients were included in the study, of which 146 (91.8%) were CA
      while 13 (8.2%) were AA. Mean duration of PD was 28.3 months for CA patients and
      16.8 months for CA patients (P=0.436). There was no significant difference in
      final change in curvature CA and AA patients (15.9 degrees  vs. 13.1 degrees 
      respectively, P=0.445). There was no statistically significant difference in
      frequency of TRAEs between CA patients (17, 12%) and AA patients (0, 0%)
      (P=0.208). Conclusions: Although racial variations in efficacy and safety of CCH
      in patients with PD have not been addressed in the literature, preliminary
      results from our study suggest that CCH therapy may be equally efficacious and
      safe in both CA and AA men. There was no statistically significant difference in
      final change in curvature, International Index of Erectile Function (IIEF)
      scores, penile length, or TRAEs after CCH treatment between CA and AA patients.

PMID- 29184789
TI  - Effect of collagenase Clostridium histolyticum on penile vascular and
      morphological parameters in patients with Peyronie's disease.
AB  - Background: To examine the changes in penile vascular parameters after the
      administration of collagenase Clostridium histolyticum (CCH) in patients with
      Peyronie's disease (PD). Methods: We retrospectively reviewed the records for all
      patients treated with CCH for PD between 04/2014 and 05/2017 who underwent penile
      duplex Doppler ultrasound (PDDU) after pharmacologically induced erection both
      before and after four cycles of CCH treatment. The primary outcomes measured were
      changes in peak systolic velocity (PSV), end diastolic velocity (EDV), and
      resistive index (RI) after CCH treatment. Paired t-tests, chi-squared tests, and
      correlation coefficients were performed between functional and vascular
      parameters before and after four rounds of CCH to determine statistical
      significance (P<0.05). Results: A total of 51 patients were included in the
      study. After four cycles of CCH therapy, there was no statistically significant
      change in PSV, EDV, RI, or International Index of Erectile Function score when
      compared to baseline. Similarly, there was no correlation between vascular
      parameters and change in curvature. There was a statistically significant change
      in penile curvature (60+/-16.9 to 40.8+/-14.9, P<0.001) and erect penile
      circumference (11.6+/-1.0 to 11.9+/-1.0 cm, P<0.05) after treatment. Conclusions:
      In spite of a significant change in penile curvature, this change did not
      correlate with changing penile vascular or morphological parameters. Overall, CCH
      therapy seems to have a negligible impact on penile vasculature, furthering
      evidence of its favorable safety profile.

PMID- 29184790
TI  - Factors associated with acutely elevated serum creatinine following radical
      tumour nephrectomy: the Correlates of Kidney Dysfunction-Tumour Nephrectomy
      Database study.
AB  - Background: To identify factors associated with acutely elevated serum creatinine
      (SCr) within 7 days of radical tumour nephrectomy. Methods: The study population
      consisted of 130 consecutive patients managed for renal tumours. The primary
      outcome was acute kidney injury (AKI) (defined as SCr increase >=50% above
      baseline), assessed using multivariable logistic regression analysis. The
      secondary outcome was SCr percentage increase, assessed using multivariable
      linear regression analysis. Results: Following nephrectomy, the mean percentage
      increase in SCr in the first week was 55%+/-29%, and 77 (59%) patients
      experienced AKI. Independent predictors of AKI post-nephrectomy were male gender
      [adjusted odds ratio (OR): 2.67; 95% confidence interval (95% CI): 1.01, 6.93],
      urine albumin-creatinine ratio (OR: 0.66; 95% CI: 0.47, 0.91), preoperative
      estimated glomerular filtration rate (eGFR) (OR: 1.03; 95% CI: 1.00, 1.05),
      laparoscopic nephrectomy (OR: 3.02; 95% CI: 1.00, 9.12), and non-clear cell renal
      cell carcinoma (RCC) (OR: 2.93; 95% CI: 1.04, 8.29). Independent predictors of a
      SCr increase were male gender (beta: 12.0; 95% CI: 2.69, 21.3), urine albumin
      creatinine ratio (beta: -3.36; 95% CI: -6.55, -0.16), preoperative eGFR (beta:
      0.38; 95% CI: 0.10, 0.66), laparoscopic nephrectomy (beta: 12.7; 95% CI: 1.05,
      24.3) and obesity (beta: 9.94, 95% CI: 0.61, 19.3). Conclusions: Male gender,
      albuminuria, eGFR and laparoscopic nephrectomy independently associated with
      acutely elevated serum creatinine following radical tumour nephrectomy.

PMID- 29184791
TI  - Comprehensive pelvic floor physical therapy program for men with idiopathic
      chronic pelvic pain syndrome: a prospective study.
AB  - Background: Male chronic pelvic pain syndrome (CPPS) is a heterogeneous
      constellation of symptoms that causes significant impairment and is often
      challenging to treat. In this prospective study, we evaluated men with CPPS who
      underwent comprehensive pelvic floor physical therapy (PFPT) program. We used the
      previously validated Genitourinary Pain Index (GUPI) to measure outcomes.
      Methods: We included 14 men who underwent physical therapy for idiopathic CPPS
      from October 2015 to October 2016. Men with clearly identifiable causes of pelvic
      pain, such as previous surgery, chronic infection, trauma, prostatitis and
      epididymitis were excluded. Treatment included: (I) manual therapy (internal and
      external) of pelvic floor and abdominal musculature to facilitate relaxation of
      muscles; (II) therapeutic exercises to promote range of motion, improve
      mobility/flexibility and strengthen weak muscles; (III) biofeedback to facilitate
      strengthening and relaxation of pelvic floor musculature; (IV) neuromodulation
      for pelvic floor muscle relaxation and pain relief. GUPI questionnaires were
      collected at initial evaluation and after the 10th visit. Higher scores reflect
      worse symptoms. Previous validation of the GUPI calculated a reduction of 7
      points to robustly predict being a treatment responder (sensitivity 100%,
      specificity 76%) and a change in 4 points to predict modest response. Data are
      presented as medians (ranges). Results: A total of 10 patients completed 10
      visits, and the remaining four patients completed between 5 and 9 visits. The
      median National Institute of Health-Chronic Prostatitis Symptom Index (NIH-CPSI)
      score at initial evaluation was 30.8 [16-39] and decreased to 22.2 [7-37] at the
      tenth visit. Five of the 10 patients (50%) in the study had a reduction of
      greater than 7 points indicating a robust treatment response, and two (20%) had a
      change of greater than 4 indicating moderate response. Three patients (30%) did
      not have any meaningful change in NIH-CPSI and the remaining four are in the
      process of completing 10 sessions. Duration of therapy appears to predict
      treatment response. Longer duration has better response. Conclusions: Male CPPS
      is difficult to treat and often requires a multimodal approach. Based on the
      results of our pilot study, pelvic floor rehabilitation may be an effective
      treatment option for select patients. A larger study with a control group is
      needed to validate the routine use of pelvic floor rehabilitation in men with
      CPPS and predict characteristics of men who would respond to therapy.

PMID- 29184792
TI  - Significance of positive semen culture in relation to male infertility and the
      assisted reproductive technology process.
AB  - There are currently no WHO guidelines on the indications for semen culture;
      however, semen cultures are performed in the evaluation of male infertility and
      the assisted reproductive technology (ART) process. The relevance and
      significance of positive semen cultures is widely debated in the literature, with
      no current consensus on the usefulness of this test in relation to male
      infertility. We review the pathogenic mechanisms of potentially pathogenic
      bacteria, general bacteria, urethral flora, and skin flora on sperm parameters.
      We also present, possible routes of semen contamination, measures to reduce
      contamination, and the clinical significance of culture contamination. First, it
      is critical to distinguish round cells in semen as leukocytes from immature germ
      cells. Second, it is critical to distinguish leukocytospermia from infected semen
      in order to guide management.

PMID- 29184793
TI  - Management of the small renal mass.
AB  - The increasing use of cross-sectional imaging has led to an increase in the
      diagnosis of incidental small renal masses (SRMs). About 20% of such masses are
      benign, while a significant proportion of malignant SRMs demonstrate slow growth
      kinetics and non-aggressive histologic features. Given these characteristics,
      lesions that were traditionally treated surgically are increasingly managed with
      less aggressive approaches. Further contributing to the evolving management
      paradigm is accumulating evidence supporting the safety of active surveillance
      and the efficacy of percutaneous renal mass biopsy in guiding management
      decisions. This review first discusses the epidemiology and diagnostic work-up of
      SRMs. The available management options are then examined, with emphasis placed on
      the clinical factors considered in selecting an appropriate approach. The
      existing evidence and long-term outcomes of each strategy are discussed. Finally,
      an overview of the current paradigm for the management of a patient with a SRM is
      provided. The goal is to provide physicians with the necessary understanding to
      appropriately manage this increasingly common condition.

PMID- 29184795
TI  - Amniotic therapeutic biomaterials in urology: current and future applications.
AB  - To examine the rationale and applications of amniotic tissue augmentation in
      urological surgery. Published literature in English-language was reviewed for
      basic science and clinical use of amniotic or amnion-chorionic tissue in
      genitourinary tissues. Basic science and animal studies support the likely
      benefit of clinical applications of amnion-derived tissues in a variety of
      urologic interventions. The broad number of properties found in amniotic
      membrane, coupled with its immunologically privileged status presents a number of
      future applications in the urological surgical realm. These applications are in
      their clinical infancy and suggest that further studies are warranted to
      investigate the use of these products in a systematic fashion.

PMID- 29184794
TI  - Should we expand the indications for varicocele treatment?
AB  - Current guidelines suggest that treatment of varicocele should be considered in
      patients with clinically palpable disease and abnormal semen parameters. However,
      the clinicians are often challenged with the decision whether to treat varicocele
      in patients with testicular pain or low testosterone levels. Moreover, varicocele
      is highly associated with DNA fragmentation due to the oxidative stress and it
      has been demonstrated that surgical repair of varicocele ameliorates oxidative
      stress markers and consequently the sperm DNA integrity. These new markers could
      have an adjunctive role to standard semen parameters especially when normal semen
      analysis is found in adult men with conventional methods. This review presents a
      contemporary overview of the rationale for varicocele treatment, as well as of
      the relationship between varicocele and other novel parameters such as DNA
      fragmentation index and reactive oxygen species. We will also discuss data from
      several recent series demonstrating that surgical treatment and especially
      microsurgical approach could resolve testicular pain, increase testosterone
      levels and fertility rate both in patients with non-obstructive azoospermia as
      well as in normozoospermia men. The correlation with progressive testicular
      failure will be also examined. We hope that this overview will provide clinicians
      with an evidence-based approach to managing these unanswered and conflicting
      topics.

PMID- 29184796
TI  - Oncofertility in sarcoma patients.
AB  - Treatment for sarcoma can significantly decrease fertility, both due to the
      irradiation of gonads, and the impact of chemotherapy on gametogenesis.
      Infertility in cancer survivors causes significant regret and decreased quality
      of life in their adulthood. As this cancer mainly affects children and young
      adults, fertility preservation is an essential part of survivorship care, however
      it remains one of the least implemented services in adolescent and young adult
      cancer patients. Success of fertility preservation is highly dependent on the
      referral prior to oncologic treatment. Early patient counseling with possible
      consult with oncofertility specialists should be offered to every oncologic
      patient in reproductive age or younger. There are several options available and
      in continuous evolution for fertility preservation. Cryopreservation of sperm and
      oocytes constitutes nowadays the standard of care, and should be offered to all
      patients. Other methods currently under development will potentially bring in the
      future reliable options for fertility preservation in a wider range of patients,
      such as those in pre-pubertal age at the time of diagnosis, or with an
      insufficient sperm count for semen banking. These include testicular sperm
      extraction (TESE), autologous ovarian tissue transplant, and in vitro maturation
      of gametes. Novel therapies such as molecular-targeted agents offer a safer
      toxicity profile regarding fertility, but further research is required to
      evaluate their impact on the long term, both alone and in combination therapies.
      Difficulties to access fertility preservation and its costs remain a significant
      impediment for many patients in need. Warranting access to all sarcoma patients
      should be a priority in all healthcare professionals involved in their care.

PMID- 29184798
TI  - Successful management of cavernosal artery pseudoaneurysm using microcoil
      embolization.
AB  - Erectile dysfunction (ED) is a common condition among men and has several causes.
      Among men under the age of 40, pelvic or perineal trauma is the most common cause
      of ED. Pelvic or perineal trauma often results in arterial injury as the likely
      mechanism of ED. We present the case of a 14-year-old male diagnosed with a
      pseudoaneurysm causing arteriogenic ED secondary to blunt force trauma to the
      perineum. We successfully managed arteriogenic ED with superselective
      embolization using microcoils. We also conclude through a review of the
      literature that microcoil and Gelfoam yield similar outcomes. We believe that it
      is important for urologists to be familiar with the various treatment techniques
      used by interventional radiologists in order to properly manage post-traumatic
      arteriogenic ED.

PMID- 29184799
TI  - Liposarcoma in the spermatic cord presenting as an inguinal swelling.
AB  - Liposarcoma in the spermatic cord is a rare condition with an incidence of 1 per
      2.5 million. The condition can present as paratesticular pain and a quick
      diagnosis is important in order to ensure proper treatment and to improve the
      prognosis. We describe a case of a 69-year-old man who suffered from long-lasting
      swelling in the inguinal area and experienced increasing pain through a period of
      2 weeks. Due to increasing pain and fast growing swelling, an exploration of the
      inguinal area was performed and peroperatively a tumour in the spermatic cord was
      found. Subsequent histological examination revealed a de-differentiated
      liposarcoma.

PMID- 29184797
TI  - Etiologic classification, evaluation, and management of hematospermia.
AB  - Hematospermia is defined by the presence of blood in the semen typically
      occurring in men younger than 40 years of age. Symptoms can occur due to a
      multitude of reasons, but are usually benign and self-limiting, requiring no
      additional treatment or evaluation. Despite this, the condition often impairs
      quality of life due to associated anxiety and must be taken seriously by the
      patient and the physician, particularly if recurrent, refractory, and painful.
      The etiology of hematospermia can be classified into inflammatory, infectious,
      lithiasis, cystic, obstructive, tumoral, vascular, traumatic, iatrogenic, and
      systemic origin. Alternatively, it can also be divided into subcategories based
      on anatomical origins such as prostate, bladder, spermatic cord, seminal
      vesicles, or epididymis. A complete history and physician examination, laboratory
      testing, and a variety of invasive and non-invasive imaging and instrumentation
      modalities can help to identify and treat the underlying pathology promptly.

PMID- 29184800
TI  - Suspected penile fracture: to operate or not to operate?

PMID- 29184801
TI  - Predicting the biological behavior of non-muscle-invasive bladder cancer: from
      histology to molecular taxonomy.

PMID- 29184802
TI  - Improving outcome and prognosis prediction in non-muscle invasive bladder cancer
      using a gene expression score.

PMID- 29184803
TI  - Complications after salvage radical prostatectomy: vesicourethral anastomosis
      leaks and possible prevention.

PMID- 29184804
TI  - A call for more responsible use of Assisted Reproductive Technologies (ARTs) in
      male infertility: the hidden consequences of abuse, lack of andrological
      investigation and inaction.

PMID- 29184805
TI  - Growth perturbations from stimulant medications and inhaled corticosteroids.
AB  - Stimulant medications for the treatment of attention deficit hyperactivity
      disorder (ADHD) and inhaled corticosteroids (ICS) for the treatment of asthma are
      two classes of medications that are commonly prescribed in pediatrics. Among
      other adverse effects of these medications, growth attenuation has long been a
      focus of investigation. With stimulants, growth deficits of 1-1.4 cm/year have
      been observed in the short term, mainly in the first 2 years of treatment, in a
      dose-dependent manner. Long-term studies on stimulants have reported divergent
      effects on growth, with many studies showing no clinically significant height
      deficits by adulthood. The study that followed the largest cohort of children on
      stimulants, however, reported an overall adult height deficit of 1.29 cm in
      subjects who had received stimulant medications, with mean adult height deficit
      of 4.7 cm among those taking the medication consistently. With ICS use, mild
      growth suppression is seen in the short term (particularly in the first year of
      therapy) with growth rates reduced by 0.4-1.5 cm/year. Available current evidence
      indicates that the impact of ICS use on adult height is not clinically
      significant, with effects limited to 1.2 cm or less. There is significant
      individual variability in growth suppression with ICS use, with the specific
      pharmacologic agent, formulation, dose exposure, age, puberty, medication
      adherence, and timing of administration being important modifying factors. Based
      on currently available evidence, the therapeutic benefits of ICS for management
      of asthma and stimulant medications for management of ADHD outweigh the potential
      risk for growth suppression. Strategies to minimize growth attenuation and other
      potential adverse effects of these medications include using the lowest
      efficacious dose, frequent assessments and dose titration. Particular vigilance
      is essential with concomitant use of multiple medications that can attenuate
      growth and to evaluate for potential adrenal insufficiency from ICS use.

PMID- 29184806
TI  - Polycystic ovary syndrome in adolescence: diagnostic and therapeutic strategies.
AB  - Controversy continues about the underlying etiopathogenesis, diagnostic criteria,
      and recommendations for polycystic ovary syndrome (PCOS) in adolescents. Recent
      literature has recognized these deficiencies and evidence based expert
      recommendations have become more available. The purpose of this chapter is to
      offer primary care providers a practical understanding and approach to the
      diagnosis and treatment of PCOS in adolescents. Although the presence of
      polycystic ovary morphology (PCOM) is included as a key diagnostic criterion of
      PCOS in adults, it is currently not recommended for the diagnosis in adolescents.
      As such, the diagnosis of PCOS in adolescents currently hinges on evidence of
      ovulatory dysfunction and androgen excess. Recommended evidence of ovulatory
      dysfunction includes: consecutive menstrual intervals >90 days even in the first
      year after menstrual onset; menstrual intervals persistently <21 or >45 days 2 or
      more years after menarche; and lack of menses by 15 years or 2-3 years after
      breast budding. Recommended evidence of androgen excess include: moderate to
      severe hirsutism; persistent acne unresponsive to topical therapy; and persistent
      elevation of serum total and/or free testosterone level. Importantly, a
      definitive diagnosis of PCOS is not needed to initiate treatment. Treatment may
      decrease risk of future comorbidity even in the absence of a definitive
      diagnosis. Deferring diagnosis, while providing symptom treatment and regular/
      frequent follow-up of symptomology, is a recommended option. The treatment
      options for PCOS should be individualized to the presentation, needs, and
      preferences of each patient. Goals of treatment are to improve quality of life
      and long-term health outcomes. Lifestyle modifications remain first-line
      management of overweight and obese adolescents with PCOS. Combined oral
      contraceptives (COC) are first line pharmacotherapy for management of menstrual
      irregularity and acne, and metformin is superior to COCs for weight reduction and
      improved dysglycemia. COCs and metformin have similar effects on hirsutism, but
      often need to be paired with other treatment modalities to achieve further
      improvement of cutaneous symptoms. Clinicians should be cognizant that PCOS is
      associated with significant metabolic and psychological comorbidity and screen
      for these issues appropriately.

PMID- 29184807
TI  - Zoledronic acid in pediatric metabolic bone disorders.
AB  - Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been
      increasingly used in children with primary and secondary osteoporosis due to its
      convenience of shorter infusion time and less frequent dosing compared to
      pamidronate. Many studies have also demonstrated beneficial effects of ZA in
      other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD),
      chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review
      summarizes pharmacologic properties, mechanism of action, dosing regimen, and
      therapeutic outcomes of ZA in a variety of metabolic bone disorders in children.
      Several potential novel uses of ZA are also discussed. Safety concerns and
      adverse effects are also highlighted.

PMID- 29184808
TI  - Recovery of steroid induced adrenal insufficiency.
AB  - Secondary adrenal insufficiency can result from insufficient stimulation of the
      adrenal glands due to inadequate secretion or synthesis of adrenocorticotropic
      hormone (ACTH). This can be caused by hypopituitarism, central nervous system
      injury (tumors, radiation, and surgery) or long-term glucocorticoid therapy.
      Glucocorticoids were introduced in the 1950s, and have been used for their anti
      inflammatory and other pharmacological effects, and also as replacement therapy
      for adrenal insufficiency. However, chronic glucocorticoid use may lead to
      suppression of the hypothalamic pituitary adrenal axis through negative feedback.
      This may lead to secondary adrenal insufficiency. Typically, the hypothalamic
      pituitary adrenal axis recovers after cessation of glucocorticoids, but the
      timing of recovery can be variable and can take anywhere from 6-12 months.
      Understanding the effect of exogenous glucocorticoids on the hypothalamic
      pituitary adrenal axis, recovery of the axis, and tests used to assess the
      recovery, are crucial to avoid prescribing unnecessary steroid replacement or
      missing a critical diagnosis with detrimental consequences.

PMID- 29184809
TI  - Review of Prader-Willi syndrome: the endocrine approach.
AB  - Prader-Willi syndrome (PWS) is a complex genetic disorder with implications on
      the endocrine and neurologic systems, metabolism, and behavior. Early in life,
      PWS is characterized by hypotonia and failure to thrive, followed by obesity and
      hyperphagia. Patients with PWS develop hypothalamic dysfunction which may lead
      growth hormone deficiency (GHD), hypogonadism, hypothyroidism, adrenal
      insufficiency, and poor bone mineral density (BMD). In addition to hypothalamic
      dysfunction, individuals with PWS have increased risk for obesity which may be
      complicated by metabolic syndrome and type 2 diabetes mellitus (T2DM). In this
      paper, we will review the current literature pertaining to the endocrine concerns
      of PWS and current recommendations for screening and management of these
      conditions.

PMID- 29184810
TI  - Ophthalmic manifestations of endocrine disorders-endocrinology and the eye.
AB  - Disorders of the endocrine system usually manifest in a multi-organ fashion. More
      specifically, many endocrinopathies become apparent in the eye first through a
      variety of distinct pathophysiologic disturbances. The eye provides physicians
      with valuable clues for the recognition and management of numerous systemic
      diseases, including many disorders of the endocrine pathway. Recognizing
      ophthalmic manifestations of endocrine disorders is critical not only for rapid
      diagnosis and treatment, but also to prevent significant morbidity and mortality.
      In this review, we discuss relevant ophthalmic findings associated with key
      disorders of the pancreas, thyroid gland, and hypothalamic-pituitary axis, as
      well as with multiple hereditary endocrine syndromes. We have chosen to focus on
      diabetes mellitus (DM), Graves' ophthalmopathy, pituitary tumors, and some less
      common disorders that underscore the unique relationship between the eye and the
      endocrine system.

PMID- 29184811
TI  - Dermatologic manifestations of endocrine disorders.
AB  - The skin serves as a window for clinicians to understand, diagnose, and monitor
      endocrine disease. Dermatologic manifestations of endocrinopathies contribute
      significantly to an individual's health and quality of life. In this review, we
      outline various disorders of the hypothalamic-pituitary axis, thyroid gland,
      pancreas, adrenal gland, and androgen axis as well as hereditary endocrine
      syndromes. In acromegaly, glycosaminoglycan deposition contributes to a
      thickening of skin and soft tissue, which manifests as coarsening and enlargement
      of facial and acral structures. Stimulation of the thyrotropin receptor in
      hyperthyroidism results in mesenchymal tissue proliferation and consequent
      pretibial myxedema; other associated cutaneous features include onycholysis, and
      hyperhidrosis. Individuals with hypothyroidism exhibit cold, dry skin and brittle
      hair as well as a jaundice-like appearance due to carotene excess. The cutaneous
      features of diabetes mellitus (DM), mediated to a large extent by hyperglycemia
      and hyperinsulinemia, include necrobiosis lipoidica diabeticorum (NLD), diabetic
      dermopathy, and acanthosis nigricans. Pediatric patients with Cushing's syndrome
      almost invariably present with truncal obesity and growth retardation; disruption
      of collagen formation and the catabolic effects of hypercortisolism result in
      skin atrophy and purple abdominal striae. In patients with Addison's disease,
      generalized hyperpigmentation, secondary to elevated levels of melanocyte
      stimulating hormone (MSH), is most prominent in sun-exposed areas. Due to
      hyperandrogenism, individuals with polycystic ovarian syndrome (PCOS) often
      exhibit hirsutism, acne vulgaris, and androgenetic alopecia. In multiple
      endocrine neoplasia (MEN) syndromes, specific gene mutations may lead to
      angiofibromas, lichen amyloidosis, and ganglioneuromas. Disruptions of immune
      regulation result in autoimmune polyglandular syndromes (APS) and associated
      clinical features including chronic mucocutaneous candidiasis, vitiligo, and
      alopecia areata. This paper highlights the underlying pathophysiology,
      dermatologic manifestations, and treatment of the aforementioned endocrine
      disorders.

PMID- 29184812
TI  - Fertility counseling and preservation: considerations for the pediatric
      endocrinologist.
AB  - Infertility is a distressing consequence of numerous pediatric medical conditions
      and treatments. The field of pediatric fertility preservation has expanded
      rapidly over the past decade, and clinical guidelines emphasize the importance of
      discussing infertility risk and fertility preservation options with patients and
      families in a timely manner. Understanding the various mechanisms and
      presentations of fertility issues across diagnoses is imperative to provide
      counseling to patients and families, and identify individuals who may benefit
      from fertility preservation. The goals of this manuscript are to outline current
      fertility preservation options in pediatrics, review populations at-risk for
      infertility that are seen in pediatric endocrinology, and discuss other important
      issues related to fertility preservation including ethical considerations.

PMID- 29184813
TI  - Disorders/differences of sex development (DSDs) for primary care: the approach to
      the infant with ambiguous genitalia.
AB  - The initial management of the neonate with ambiguous genitalia can be a very
      stressful and anxious time for families, as well as for the general practitioner
      or neonatologist. A timely approach must be sensitive and attend to the
      psychosocial needs of the family. In addition, it must also effectively address
      the diagnostic dilemma that is frequently seen in the care of patients with
      disorders of sex development (DSDs). One great challenge is assigning a sex of
      rearing, which must take into account a variety of factors including the
      clinical, biochemical and radiologic clues as to the etiology of the atypical
      genitalia (AG). However, other important aspects cannot be overlooked, and these
      include parental and cultural views, as well as the future outlook in terms of
      surgery and fertility potential. Achieving optimal outcomes requires open and
      transparent dialogue with the family and caregivers, and should harness the
      resources of a multidisciplinary team. The multiple facets of this approach are
      outlined in this review.

PMID- 29184814
TI  - Hypoglycemia in the preterm neonate: etiopathogenesis, diagnosis, management and
      long-term outcomes.
AB  - Glucose, like oxygen, is of fundamental importance for any living being and it is
      the major energy source for the fetus and the neonate during gestation. The
      placenta ensures a steady supply of glucose to the fetus, while birth marks a
      sudden change in substrate delivery and a major change in metabolism.
      Hypoglycemia is one of the most common pathologies encountered in the neonatal
      intensive care unit and affects a wide range of neonates. Preterm, small for
      gestational age (GA) and intra-uterine growth restricted neonates are especially
      vulnerable due to their lack of metabolic reserves and associated co-morbidities.
      Nearly 30-60% of these high-risk infants are hypoglycemic and require immediate
      intervention. Preterm neonates are uniquely predisposed to developing
      hypoglycemia and its associated complications due to their limited glycogen and
      fat stores, inability to generate new glucose using gluconeogenesis pathways,
      have higher metabolic demands due to a relatively larger brain size, and are
      unable to mount a counter-regulatory response to hypoglycemia. In this review we
      will discuss the epidemiology; pathophysiology; clinical presentation; management
      and neurodevelopmental outcomes in affected infants and summarize evidence to
      develop a rational and scientific approach to this common problem.

PMID- 29184815
TI  - Transient hypothyroidism in the newborn: to treat or not to treat.
AB  - Transient congenital hypothyroidism (CH) refers to a temporary deficiency of
      thyroid hormone identified after birth, with low thyroxine (T4) and elevated
      thyrotropin (TSH), which later recovers to improved thyroxine production,
      typically in first few months of infancy. Approximately 17% to 40% of children
      diagnosed with CH by newborn screening (NBS) programs were later determined to
      have transient hypothyroidism. Causes of transient CH are prematurity, iodine
      deficiency, maternal thyrotropin receptor blocking antibodies, maternal intake of
      anti-thyroid drugs, maternal or neonatal iodine exposure, loss of function
      mutations and hepatic hemangiomas. The classic clinical symptoms and signs of CH
      are usually absent immediately after birth in vast majority of infants due to
      temporary protection from maternal thyroxine. NBS has been largely successful in
      preventing intellectual disability by early detection of CH by performing thyroid
      function tests in infants with abnormal screening results. In this review we
      present the evidence for decision making regarding treatment vs. withholding
      treatment in infants with transient CH and present a rational approach to
      identifying transient CH based on American Academy of Pediatrics (AAP)
      recommendation.

PMID- 29184816
TI  - Type 1 diabetes: where are we in 2017?
AB  - Type 1 diabetes mellitus is a chronic state of insulin deficiency which results
      from destruction of beta cells by the immune system. The long term microvascular
      and macrovascular complications can be devastating. Since the discovery of
      insulin almost 100 years ago new medical therapies have improved the long-term
      survival for people with type 1 diabetes. Each year we come closer to discovering
      a cure but much work still needs to be done to eliminate this disease.

PMID- 29184817
TI  - Role of a registered dietitian in pediatric type 1 and type 2 diabetes.
AB  - Type 1 and type 2 diabetes are complex, chronic diseases that are best managed by
      a multidisciplinary care team. Type 1 diabetes is most commonly diagnosed in the
      pediatric population, although the prevalence of type 2 diabetes in youth is
      increasing rapidly. A registered dietitian (RD) is a critical member of the
      diabetes team who provides focused nutrition education from diagnosis and
      throughout routine follow-up care. Specifically in the pediatric population, the
      RD also assesses growth and development, as well as eating behaviors, food
      choices and meal patterns. Based on a review of research, ongoing support from an
      RD improves glycemic control and delays onset of diabetes complications. In
      addition, dietitian-led nutrition education helps better manage lipid levels and
      aids in weight management. A sample model describing RD involvement in a
      pediatric diabetes care team is discussed in further detail.

PMID- 29184818
TI  - Transition of care for patients with type 1 diabetes mellitus from pediatric to
      adult health care systems.
AB  - Planning for the transition from pediatric to adult healthcare is broadly
      understood to be beneficial to the quality of care of patients with chronic
      illness. Due to the level of self-care that is necessary in the maintenance of
      most chronic diseases, it is important that pediatric settings can offer support
      during a time when adolescents are beginning to take more responsibility in all
      areas of their lives. Lack of supportive resources for adolescents with chronic
      conditions often results in both decreased access to care and impaired health and
      function likely leading to increased medical costs later. Additionally,
      fundamental differences in health care delivery exist between pediatric and adult
      care settings. There is limited empiric data and information on best practices in
      transition care. In this article we address the importance of bridging pediatric
      and adult care settings and highlight the challenges and successes of the
      implementation of the young adult transition clinic program for patients with
      type 1 diabetes at our facility. We provide recommendations for further research
      and program implementation with the transition population.

PMID- 29184819
TI  - Psychosocial aspects of diabetes management: dilemma of diabetes distress.
AB  - Diabetes mellitus (DM) is a debilitating chronic illness with complex
      pathophysiological, psychological, and quality of life (QoL) implications
      creating a constant state of turbulence. Some of these interconnections are
      apparent to healthcare providers and are easily addressed in a routine diabetic
      clinical care. However, a large number of these hidden factors that interplay
      with each other and impact on the physical outcomes of DM goes unnoticed by
      health care providers. This is a frustrating and lonely predicament for DM
      patients making it very difficult for them to manage their illness well. At times
      these patients are mislabeled as "difficult patients". In other cases they are
      considered to have and unnecessarily treated for psychiatric illness like
      depression, other mood or anxiety spectrum disorders which they may not need. In
      recent years clinical researcher are making strides in understanding the
      emotional distress a DM patient may feel and the factors contributing or
      perpetuating diabetes distress. This article focuses on understanding the
      diabetes distress and how it impacts our patients, how to screen, assess, treat
      and eventually prevent it from happening. The paper also attempt to bring out the
      major differences between diabetes distress and common psychiatric comorbidities
      of DM including but not limiting to major depressive disorder and other
      depression spectrum disorders.

PMID- 29184820
TI  - Metabolic syndrome in children and adolescents.
AB  - Prevalence of metabolic syndrome in children and adolescents is increasing, in
      parallel with the increasing trends in obesity rates. Varying definitions of this
      syndrome have hindered the development of a consensus for the diagnostic criteria
      in the pediatric population. While pathogenesis of metabolic syndrome is not
      completely understood, insulin resistance and subsequent inflammation are thought
      to be among its main mechanistic underpinnings. Overweight and obesity are
      cardinal features, along with abnormal glucose metabolism, dyslipidemia, and
      hypertension. Other disorders associated with metabolic syndrome include fatty
      liver, polycystic ovarian syndrome (PCOS), and pro-inflammatory states.
      Prevention and management of this condition can be accomplished with lifestyle
      modifications, behavioral interventions, pharmacological and surgical
      interventions as needed.

PMID- 29184821
TI  - Approach to hypoglycemia in infants and children.
AB  - Hypoglycemia is a heterogeneous disorder with many different possible etiologies,
      including hyperinsulinism, glycogen storage disorders, fatty acid disorders,
      hormonal deficiencies, and metabolic defects, among others. This condition
      affects newborns to adolescents, with various approaches to diagnosis and
      management. This paper will review current literature on the history of
      hypoglycemia, current discussion on the definition of hypoglycemia, as well as
      etiologies, diagnosis, and management.

PMID- 29184822
TI  - Gingivitis and plaque prevention using three commercially available dentifrices:
      A comparative clinical and microbiological randomized control parallel study.
AB  - Aim: The aim of the study was to compare the clinical and microbiological
      efficacy of Group I-delmopinol dentifrice, Group II-chlorhexidine, and Group III
      triclosan-containing regularly used control dentifrice on plaque formation and
      gingivitis. Materials and Methods: A total of 45 healthy volunteer students
      fulfilling the inclusion criteria are recruited for this randomized control
      parallel study. All the individuals were randomly assigned into 3 groups
      depending on the dentifrice prescribed. After the selection of individuals,
      thorough scaling and polishing were performed for all the individuals, and in a 4
      days' washout period, they were refrained from regular oral hygiene maintenance
      and 0.9% NaCl (normal saline) rinse was prescribed to obtain plaque regrowth.
      Microbiological morphotypes were assessed using darkfield microscope. Statistical
      Analysis: The data were analyzed using the SPSS-software 19.00 program. The
      intragroup comparison of clinical parameters was done using Kruskal-Wallis ANOVA
      test, and intergroup comparison was done by Mann-Whitney U-test. The intragroup
      comparison of clinical parameters including modified staining index, the
      supragingival microbiota such as cocci, bacilli, and spirochetes scores was done
      at various study intervals using one-way ANOVA, and intergroup comparison was
      done using Tukey's multiple post hoc test. Results: The results showed that
      statistically significant correlation between Group II and Group III at 15 and 30
      days and between Group I and Group II at 30 days with cocci and bacilli but not
      spirochetes. Conclusion: Group II showed better plaque and gingivitis reduction
      compared to other active groups. To validate the results of the present study,
      further long-term studies with larger sample size and evaluation using known and
      proven study designs on gingivitis patients are needed.

PMID- 29184823
TI  - A prospective randomized controlled study: Theophylline on oxidative stress and
      steroid sensitivity in chronic obstructive pulmonary disease patients.
AB  - Objective: Oxidative stress is involved in the pathogenesis of chronic
      obstructive pulmonary disease (COPD). Corticosteroid fails to suppress
      inflammation and oxidative stress due to steroid resistance. Theophylline has an
      effect on histone deacetylase (HDAC) activity and improves steroid sensitivity in
      COPD. Given changes in oxidative stress associated with diminished corticosteroid
      effects, a clinical study in which antioxidants and free radicals are estimated
      can suggest a correlation between antioxidants, theophylline, and corticosteroid
      sensitivity. Materials and Methods: A randomized controlled study was conducted
      in 60 participants divided into 4 groups: Group I (controls) - 15 normal healthy
      volunteers, Group II - COPD patients who received theophylline 300 mg +
      salbutamol 8 mg, Group III - patients who inhaled budesonide 400 MUg + salbutamol
      8 mg, and Group IV - theophylline 300 mg + inhaled budesonide 400 MUg +
      salbutamol 8 mg 12 weeks. Blood samples were collected at the time of diagnosis
      and at 4-week interval for 3 months from all the groups and antioxidant
      parameters, spirometric % forced expiratory volume in 1 s (FEV1) were measured.
      Results: The mean difference between groups was analyzed using one-way ANOVA.
      There was a significant increase in antioxidant enzymes such as catalase,
      glutathione (GSH) serum transferase, (P < 0.05), reduced GSH, and superoxide
      dismutase (P < 0.01) and a significant decrease in lipid peroxidation (P < 0.01)
      at 12 weeks of the study period. Postbronchodilator FEV1 values have also shown a
      significant increase at 12 weeks (P < 0.01). Conclusion: Theophylline increases
      the expression and activity of HDAC and improves steroid sensitivity thereby
      decreases oxidative stress. Hence, novel therapeutic strategy is therefore the
      reversal of this corticosteroid resistance by increasing the expression and
      activity of HDAC achieved using corticosteroids along with theophylline.

PMID- 29184824
TI  - Smartphone usage and increased risk of mobile phone addiction: A concurrent
      study.
AB  - Objective: This study aimed to study the mobile phone addiction behavior and
      awareness on electromagnetic radiation (EMR) among a sample of Malaysian
      population. Methods: This online study was conducted between December 2015 and
      2016. The study instrument comprised eight segments, namely, informed consent
      form, demographic details, habituation, mobile phone fact and EMR details, mobile
      phone awareness education, psychomotor (anxious behavior) analysis, and health
      issues. Frequency of the data was calculated and summarized in the results.
      Results: Totally, 409 respondents participated in the study. The mean age of the
      study participants was 22.88 (standard error = 0.24) years. Most of the study
      participants developed dependency with smartphone usage and had awareness (level
      6) on EMR. No significant changes were found on mobile phone addiction behavior
      between the participants having accommodation on home and hostel. Conclusion: The
      study participants were aware about mobile phone/radiation hazards and many of
      them were extremely dependent on smartphones. One-fourth of the study population
      were found having feeling of wrist and hand pain because of smartphone use which
      may lead to further physiological and physiological complication.

PMID- 29184825
TI  - A comparative evaluation of diclofenac sodium transdermal patch, oral diclofenac
      sodium with intramuscular injections of diclofenac sodium in patients suffering
      from oral pain: A randomized control trial.
AB  - Background: Newer drug delivery systems such as transdermal patches using pain
      relieving or modifying agents emerged as a mainstream treatment protocol for
      management of pain on the outpatient basis. The administration of diclofenac 100
      mg in the transdermal patch in the patients having dental pain due to
      periapical/periodontal infections was evaluated. Materials and Methods: Ninety
      patients of either gender, between 18 and 80 years were divided into 3 groups
      (Group A - oral medication, Group B - transdermal patch, Group C - intramuscular
      group). Patients at the Dental Department with pain from periapical/periodontal
      pathologies were explained about the procedure of analgesia. With written
      consent, 100 mg diclofenac sodium transdermal patches were prescribed to patients
      who opted their use in pain control for 2 consecutive days. A visual analog scale
      was provided for all patients assessing the pain intensity during the study.
      Results: Significant difference in the mean percentage reduction in visual analog
      scale (VAS) score among the three groups at day 1 and 2 (P < 0.001). Post hoc
      test showed that intramuscular (IM) and oral groups had significantly higher mean
      VAS score than patch group. Conclusion: Diclofenac administered through oral and
      IM routes showed significant improvement in pain relief when compared to the
      transdermal route. However, diclofenac transdermal patches have shown significant
      improvement in VAS score between the baseline and consecutive days and can be
      used in mild pain with lower adverse events.

PMID- 29184826
TI  - Isolation and identification of probiotic Lactobacillus from local dairy and
      evaluating their antagonistic effect on pathogens.
AB  - Objective: Probiotics such as lactobacilli prevent the development of a wide
      range of human and animal's pathogens. The aim of this study was evaluation of
      antagonistic effect of isolated lactobacilli from local dairy products against
      three standard strains of Staphylococcus aureus, Bacillus subtilis, and
      Pseudomonas aeruginosa. Materials and Methods: Twenty samples of local dairy
      products including cow milk, buffalo milk, cheese, and yogurt were collected from
      different areas of Ahwaz city. Antimicrobial disc diffusion method was applied on
      S. aureus (ATCC-6538), B. subtilis (ATCC-12711), and P. aeruginosa (ATCC-27853).
      Antimicrobial effects of isolates were evaluated by disc diffusion test on
      Mueller-Hinton agar medium plated with three pathogens. Results: Obtained results
      showed that only three strains of isolated lactobacilli of local dairy samples
      had inhibitory effects on understudy pathogens including Lactobacillus
      alimentarius, Lactobacillus sake, and Lactobacillus collinoides. All three
      isolates showed moderate activity (inhibition zone <15 mm) except of L.
      collinoides and L. alimentarius that had relatively strong activity (inhibition
      zone >=15 mm) against P. aeruginosa and B. subtilis, respectively. Conclusion:
      These bacteria can be raised for the production of various kinds of food,
      pharmaceutical products, and functional foods.

PMID- 29184827
TI  - Development of a binary carrier system consisting polyethylene glycol 4000 -
      ethyl cellulose for ibuprofen solid dispersion.
AB  - Background and Objective: One of the established strategies to improve solubility
      and dissolution rate of poorly water-soluble drugs is solid dispersion (SD).
      Polyethylene glycol (PEG) is used as common carrier despite its stability problem
      which may be overcome by the addition of hydrophobic polymer. The present
      research aimed to develop an SD formulation with ibuprofen, a poor water-soluble
      BCS Class II drug as active pharmaceutical ingredient (API) and PEG 4000-ethyl
      cellulose (EC) as binary carrier. Methods: Melt mixing SD method was employed
      using a ratio of API: binary carrier (1:3.5 w/w) (SDPE). Another SD was prepared
      using only PEG (SDP) as a carrier for comparative study. The developed
      formulation was evaluated using optical microscopy, scanning electron microscopy
      (SEM), determination of moisture content, differential scanning calorimetry
      (DSC), in vitro dissolution test, attenuated total reflection-Fourier transform
      infrared spectroscopy (ATR-FTIR) and flow properties. Results: SEM and DSC
      indicated the conversion of crystalline ibuprofen to fine partly amorphous solid
      dispersion, which was responsible for the increase in dissolution rate of SD than
      a physical mixture. The release characteristics within 1 h from the higher to the
      lower value were the SDPE> SDP> physical mixture. Flow property evaluation using
      the angle of repose showed no difference between SD and PM. However, by Carr
      index and Hausner ratio, the flow properties of SDPE was excellent. Conclusion:
      The SD formulation with the PEG 4000-EC carrier can be effective to enhance in
      vitro dissolution of ibuprofen immediate release dosage form.

PMID- 29184828
TI  - Radioprotective effect of hesperidin on reducing oxidative stress in the lens
      tissue of rats.
AB  - Introduction: Oxidative stress is a common factor in cataract. Considering the
      antioxidant properties of hesperidin as a flavanone glycoside from the flavonoid
      family with radioprotective effect, this study aimed to determine the protective
      effect of this flavanone glycoside on reducing oxidative stress in the eye lens
      tissue of mature rats caused by gamma irradiation. Materials and Methods: A total
      of 48 adult rats were randomly divided into six groups, namely, control, Dimethyl
      sulfoxide (DMSO), hesperidin, radiation, radiation + DMSO, and radiation +
      hesperidin. 15 Gy irradiation was carried out using Cobalt-60 teletherapy
      instrument with a source-to-surface distance of 80 cm at a dose rate of 98.5
      cGy/min. 2 days following irradiation, we removed the rats' lenses and analyzed
      them to determine the effects of hesperidin. Results: The comparison of control
      and intervention groups after irradiation showed that malondialdehyde (MDA) level
      in the lens tissue was significantly higher in the irradiation groups than the
      control group. Furthermore, a significant difference between radiation and
      radiation + hesperidin groups were observed. The level of glutathione (GSH) in
      the lens tissue was significantly lower in the irradiation groups compared to the
      control group. Nonetheless, significant elevation of GSH in the radiation +
      hesperidin group compared to radiation group was seen. Conclusions: Radiation
      exposure reduced GSH and enhanced MDA levels in the lens tissue. However, GSH and
      MDA levels were modulated after hesperidin consumption. These results show the
      antioxidative properties of hesperidin in the lens and demonstrated that
      radiation complications such as cataract can be reduced by hesperidin through
      reducing oxidative stress.

PMID- 29184829
TI  - Platelets and Their Pathways in Dentistry: Systematic Review.
AB  - Advancing research in medicine and technology has benefitted the mankind
      immensely with its contribution toward an improved life quality and increased
      life expectancy. The inability of a human body to autoregenerate has resulted in
      an increased demand for newer and healthier tissues and organs. Therefore, the
      restoration of naturally replicated tissue components has become a subject of
      interest for the scientific community lately. There was felt an intense quest for
      promoting strategies that could restore tissue regeneration and fuel the field of
      regenerative medicine. It was then the role of platelets was accounted for its
      wound healing and regenerative effects. Consequently, the use of platelet
      concentrates to improve wound healing, and bone formation was explored, which was
      considered to be possible because platelets contain high quantities of growth
      factors which would be able to stimulate cell proliferation, matrix remodeling,
      and angiogenesis, thereby establishing a new era of research with the successful
      application of innovative medical therapies focused on healing damaged tissues or
      regenerate the affected organs.

PMID- 29184830
TI  - Orofacial Bacterial Infectious Diseases: An Update.
AB  - Objectives: Most of the oral infections with odontogenic origin are very common
      and can be treated by tooth extraction, endodontic therapy, or surgical
      treatment. Other infectious lesions are the manifestations of systemic diseases
      such as tuberculosis and syphilis. Skin and underlying subcutaneous tissue,
      fascia, or muscle is also involved with infectious diseases which range from
      superficial epidermal infections to very serious necrotizing fasciitis. Materials
      and Methods: An extensive literature in PubMed, Google Scholar, and Scopus search
      was performed from 1980 to 2017. All related articles were analyzed. Results:
      Most oral infections have odontogenic origin. Skin and the underlying
      subcutaneous tissue, fascia, or muscles are also involved with infectious
      diseases which range from superficial epidermal infections to very serious
      necrotizing fasciitis. Conclusions: These facts prove that the interaction
      between the oral cavity, face skin, and the other organs can risk the people's
      life. The establishment of a correct diagnosis and recognition of clinical
      findings are the crucial steps to support and improve professional orofacial
      health status.

PMID- 29184831
TI  - A Cone Beam Computed Tomography of the Root Canal Morphology of Maxillary
      Anterior Teeth in an Institutional-Based Study in Chennai Urban Population: An In
      vitro Study.
AB  - Aim: This study aims to investigate the root canal anatomy of human extracted
      permanent maxillary anterior teeth in patients reporting to our dental
      institution in Chennai using cone beam computed tomography (CBCT). Materials and
      Methods: A total of 285 maxillary anterior teeth comprising of 100 central
      incisors, 85 lateral incisors, and 100 canines extracted from various patients
      reporting to our institution were studied. The number of roots and number of
      canals were assessed; following which, the root canal anatomy of each tooth was
      evaluated for the canal pattern using CBCT. The collected data were analyzed
      using IBM. SPSS statistics software 23.0 version. Results: All the teeth examined
      were observed to be single rooted. All maxillary central incisors displayed Type
      I (100%) pattern whereas maxillary laterals and canines displayed canal
      variations. In maxillary laterals, Type I pattern (98%) was most prevalent
      followed by Type II (2%) configuration. Maxillary canines revealed a predominant
      Type I (96%) canal pattern followed by Type II (3%) and Type III (1%).
      Conclusion: A varied root canal anatomy was observed in maxillary anterior teeth
      among Chennai urban population in this institutional-based study. The most
      frequent canal pattern reported in the maxillary anterior dentition was Type I.
      Type II was observed in both maxillary lateral incisors and maxillary canines
      whereas Type III canal configuration was reported only in maxillary canines.

PMID- 29184832
TI  - Cross-cultural Adaptation and Psychometric Properties of the Indonesia Version of
      the Scale of Oral Health Outcomes for 5-Year-Old Children.
AB  - Objective: Oral health-related quality of life (OHRQoL) questionnaires have been
      administered to children older than 6 years. Currently, the scale of oral health
      outcomes for 5-year-old children (SOHO-5) has been used to determine the OHRQoL
      through self-reports and parental proxy reports of children aged <6 years. This
      study was conducted to estimate the psychometric reliability and validity after
      adapting the SOHO-5 to the Indonesian language. Materials and Methods: The cross
      cultural adaptation was tested in children aged 5 years old and their parents.
      The reliability and validity of the questionnaire were measured among 161
      kindergarten children in Jakarta, along with a clinical examination for dental
      caries. Results: Cronbach's alpha coefficients for internal consistency were 0.89
      and 0.86 for child's self-reports and parental reports, respectively. The test
      retest reliability results were excellent based on repeated administrations in 27
      children; the intraclass correlation coefficients were 0.81 and 0.94 for the
      parental reports and child's self-reports, respectively. No corrected item-total
      correlation value was lower than 0.30, allowing all items in the instrument to be
      included for data analyses. The construct validity of the child's self-reports
      showed that the Indonesian SOHO-5 total score was significantly associated only
      with the presence of dental caries (P < 0.001). The construct validity of the
      parental reports described that the SOHO-5 total score was significantly
      associated with proxy-rated oral health, the child's perceived dental treatment
      and satisfaction with the child's oral health (P < 0.001). Conclusions: This
      study showed the Indonesian version of SOHO-5 is a reliable and valid OHRQoL
      measure for 5-year-old Indonesian children.

PMID- 29184833
TI  - Comparison of Coronal Leakage in Tooth Preparation with Two Single File Systems
      and Three Obturation Techniques.
AB  - Aims and Objectives: Root canal preparation and obturation are of great
      importance in endodontics. Its purpose is to eliminate pulpal and periradicular
      disease. The aim of this study was to compare coronal bacterial microleakage in
      prepared root canals using Neoniti A1 and Reciproc files that obturated with
      lateral compaction, single cone gutta-percha, and hybrid (tapered cone/lateral
      compaction) methods. Materials and Methods: In this ex vivo study, a total of 110
      single-rooted mandibular first premolars were choose and randomly divided into
      two study groups A and B (each 45) that one group was prepared with Reciproc and
      another with Neoniti A1 and negative and positive control groups (each 10). Each
      group divided into three subgroups of 15 each and obturated using a single cone,
      lateral compaction, and hybrid (tapered cone/lateral compaction) techniques. For
      evaluation of coronal leakage, "two-chamber setup" was used. The solution of
      enterococcus faecalis culture was injected in the upper chamber and incubated. If
      the bacteria pass through the canal and obturation materials, the lower chamber
      becomes turbid. TSB medium in the lower chamber (apex) were investigated every
      day in terms of occurrence of turbidity, and the duration of occurrence of
      leakage was recorded. The data were analyzed using Chi-square test. Results: Data
      analysis showed that in each group the difference in percentages between
      subgroups was statistically significant (P = 0.003). So that the highest and the
      lowest amount of leakage in both groups were related to lateral compaction and
      hybrid techniques, respectively. Conclusion: Under the conditions of this study,
      independent of the instrument used for canal preparation, hybrid method and then
      single-cone technique, however, were more effective in the prevention of coronal
      leakage than lateral condensation technique.

PMID- 29184834
TI  - Knowledge, Attitude, and Practice of Upper-middle Class toward the Importance of
      a Pediatric Dentist.
AB  - Aims and Objectives: This study was carried out to assess the knowledge,
      attitude, and practice of upper middle class toward the importance of a pediatric
      dentist in the city of Amritsar, Punjab. Materials and Methods: A cross-sectional
      study was carried out among the parents of children belonging to upper middle
      class in the city of Amritsar. This proposed study was assessed by the
      Institutional Ethical Committee (531/IDSR/2016) and their clearance was attained.
      A total of 950 parents were selected using a convenient sampling technique, and a
      self-made questionnaire was presented to them. Responses from the parents were
      evaluated in terms of numbers and percentages and were statistically analyzed
      using SPSS for Windows release 14.0 (SPSS Inc., Chicago, IL, USA). Differences at
      the 5% level were accepted as being statistically significant. Results: The
      results of the study show limited knowledge about a pediatric dentist among the
      well-educated, well-placed, and economically sound citizens of Amritsar city.
      Consequently, the attitude and practices among this socioeconomic group are
      unconstructive and unprepared, respectively. Conclusion: Although the importance
      of taking a child to a pediatrician is a common practice among the upper and
      upper-middle classes of the society, it is clear that they do not give the same
      importance to a pediatric dentist, who is the pediatrician of dentistry.

PMID- 29184836
TI  - A Comparative Evaluation of Effect of Reinforced Autopolymerizing Resin on the
      Flexural Strength of Repaired Heat-polymerized Denture Base Resin before and
      after Thermocycling.
AB  - Aims and Objective: Denture fractures are a common problem in clinical practice.
      Despite the use of different reinforcement materials (metal wires, metal plates,
      and various types of fibers) for denture repairs, recurrent fractures are still
      common. The purpose of this study was to compare the maximum flexural loads of
      the heat-polymerized denture base resin when repaired with autopolymerizing resin
      reinforced with relatively smaller diameter metal wires and glass fibers, before
      and after thermocycling. Materials and Methods: Heat polymerized rectangular
      specimens were fabricated and repaired with autopolymerized resin and different
      reinforcement materials. Stainless steel wires, coaxial wires, beta-titanium
      wires, and glass fibers were used as reinforcement materials. Metal wires were
      sandblasted before placing in the center of the specimen along with
      autopolymerizing resin. Control specimens were repaired without any
      reinforcements. Intact heat- and self-cure specimens were also prepared for
      comparison. Half of the specimens of each group were subjected to thermocycle
      stressing (5 degrees C and 55 degrees C, 30 s dwell time) for 2000 cycles. All
      the specimens, nonthermocycled as well as thermocycled, were then tested for
      flexural strength by using 3 point flexural test in Lloyd's Universal testing
      machine at 5 mm/min crosshead speed. The maximum flexural loads (N) for each
      specimen were recorded. The readings, thus obtained, were subjected to
      statistical analysis using two-way ANOVA and Tukey's multiple comparison test.
      Results: The metal wire reinforcements increased the flexural strength of
      repaired specimens, whereas, glass fiber reinforcement produced slightly lower
      flexural strength when compared to those of control specimens, i.e., repair
      without any reinforcement. The highest flexural strength was demonstrated by
      specimens repaired with coaxial wire reinforcements (50.01 and 43.77 N before and
      after thermocycling, respectively). The increase in flexural strength with the
      use of stainless steel wire (45.12 and 41.56 N) and beta-titanium wire
      reinforcements (45.54 and 42.61N) was insignificant. Conclusions: Coaxial wire
      reinforcement produced significantly higher flexural loads than control. Increase
      in strength with stainless steel wire and beta-titanium wire was insignificant,
      whereas glass fiber reinforcement reduced the strength.

PMID- 29184835
TI  - Perceived Stress among French Dental Students and Their Opinion about Education
      Curriculum and Pedagogy.
AB  - Objectives: The purpose of this study was to identify the major sources of
      perceived stress and their relation to a student satisfaction questionnaire about
      the curriculum and the pedagogy among French dental students. Materials and
      Methods: All dental students (n = 178) from years 4 to 6 at the University of
      Montpellier (France) participated in this exploratory survey. In spring 2016, a 3
      part questionnaire was distributed during clinical sessions: the first part asked
      about sociodemographic and living conditions, the second part aimed to assess the
      students' perceived stress (Dental Environmental Stress questionnaire), and the
      third part was a satisfaction questionnaire exploring the clinical organization
      and the teaching methodologies (Student Course Experience Questionnaire). A
      Spearman's correlation test and a principal component analysis were used to
      assess the relation between the variables of the questionnaire. Results: The
      response rate was 99.4%. The most stressful items were "the number of tasks to be
      performed during clinical practice," "the waiting time before opinion from
      teachers," and "the administrative part and computer problems." Fifty-four
      percent of the students claimed to be satisfied with their studies, showing a
      score of seven or higher. There was a negative correlation between the level of
      student satisfaction and the level of perceived stress. Conclusion: Although most
      of the students were globally satisfied with their curriculum, this study
      highlighted dysfunctions in the clinical education with a level of stress
      correlated with the student's dissatisfaction. Most of all, students found that
      examinations were too stressful and that the clinical requested task quotas were
      overestimated.

PMID- 29184837
TI  - Effectiveness of an Oral Health Education Program for Obstetrician/Gynecologist
      Residents at Tufts Medical Center.
AB  - Aim and Objectives: To assess Tufts Medical Center obstetrician/gynecologist
      (OB/GYN) residents' knowledge, beliefs, and previous training in oral health and
      to assess the effect of an oral health educational seminar on their knowledge and
      beliefs. Materials and Methods: A preseminar questionnaire was distributed to the
      residents. The same questionnaire was distributed immediately after the seminar
      and 3 months later. SPSS Version 21 was used for the data analysis. Results:
      Convenience sample of 25 residents were included in the study. The mean (standard
      deviation) age of participants was 29.08 (2.47) years. Only 1 (4%) participant
      reported receiving >8 h previous training in oral health and 7 (28%) reported
      receiving <1 h of training. The nonparametric Friedman test showed a
      statistically significant difference between administrations in terms of total
      score on knowledge-based questions (P < 0.001) and some of the belief-based
      questions. The post hoc Wilcoxon signed-rank test with Bonferroni correction
      showed statistically significant improvement in the knowledge-based questions
      between pre- and post-seminar questionnaire (P = 0.002) and between preseminar
      and 3-month follow-up (P = 0.003). Conclusions: OB/GYN residents at Tufts Medical
      Center received limited training in oral health. Their knowledge improved
      significantly following the oral health educational seminar. Similar training
      modules can be brought to other OB/GYN residencies and OB/GYNs in an effort to
      enhance the symbiotic relationship between medical and dental professionals.

PMID- 29184838
TI  - Magnifying the Senescence: Impact of Oral Health on Quality of Life and Daily
      Performance in Geriatrics: A Cross-Sectional Study.
AB  - Objective: The objective of the study is to study the behavior of the GOHAI as
      well as the OIDPs as potent measures in oral health related to quality of life in
      senior citizens. Materials and Methods: An outreach program-based cross-sectional
      study conducted in Modinagar, Uttar Pradesh, India. A total of 340 study
      participants aged >60 years were selected from outreach program which were held
      between January 2017 and April 2017 based on inclusion and exclusion criterion.
      The dental health status and its influence on the self-perceived value of life
      was assessed using GOHAI and OIDP index among the participants. The data were
      estimated using Statistical Package for the Social Sciences version 21.0 (SPSS
      Inc., Chicago, IL, USA). Chi-square analysis and Pearson correlation were used to
      test the significance of the independent variables and the distinct the overall
      oral impact scores in groups with different dental status. Results: OIDP shows
      that most of the patients are suffering from eating food (57.74) and speaking
      clearly (45.96). GOHAI shows that most of the geriatric population with a lowest
      mean score of 2.12 and 2.13 were difficulty in chewing food and sorrowful with
      the condition of mouth and teeth. Similarly, a lower number of population of 3.68
      had difficulty in swallowing food. Conclusion: The prevalence of OIDPs in this
      geriatric population was high. Oral impact mainly effect their quality or value
      of life leading to difficulty in eating and verbal communication.

PMID- 29184840
TI  - Personalized medicine: An era of dosage form development.

PMID- 29184839
TI  - Correlation of Perceived Self-Rated Oral Health Status with Various Dental Health
      and Awareness Factors.
AB  - Aims and Objectives: Self-rated oral health is the key element that has a greater
      effect on quality of life and found to be authentic and logical to consider this
      as an indicator for overall oral health status. The aim was to investigate and
      identify the impact of various social and clinical factors on the perceived self
      rated oral health status (PSR-OHS). Materials and Methods: A self-administered
      questionnaire was distributed 600 patients seeking information for age, gender,
      nationality, educational level, and their last dental visit followed by 15
      questions related to social factors (patient self-rated oral health, patient
      dentist communication, literacy level of the patient, and dental neglect)
      followed by estimating the clinical oral health status (decayed, missing, and
      filled teeth [DMFT] scores as per WHO norms). Results: The results were estimated
      by a single five-point-response-scale question dichotomized into poor and good
      self-rated oral health. The average mean age for participation in the study is
      32.5 years and found to be highly significant (P < 0.01) with inverse relation
      indicating that younger patients give better PSR-OHS. There were no significant
      differences in PSR-OHS among other demographic factors. Patients visiting the
      dentist recently found to be confident about their PSR-OHS and are statistically
      significant. Pearson correlating scores of social factors and the DMFT scores
      most concerned in the present study have a significant relation with self-rated
      oral health status. Conclusions: PSR-OHS is governed by various dental health and
      awareness factors. It can be used as an important tool by a clinician to assess
      the clinical examination results which helps to achieve more effective time and
      patient management.

PMID- 29184841
TI  - Evaluation of the anesthetic effect of nasal mucosa with tetracaine 0.5% on
      hemodynamic changes and postoperative pain of septoplasty: A randomized
      controlled trial.
AB  - The nasal septum repair surgery is the dangerous operations that any stimulation
      of this area causes a large change in the rhythm of the heartbeat and blood
      pressure. This study aimed to determine the effects of tetracaine 0.5% on changes
      in heartbeat and heart rhythm, hemodynamic changes during surgery, intraoperative
      bleeding, and pain after septoplasty surgery. The irregular double-blind clinical
      trial registry of clinical trials Iran with the code number (IRCT: 20150526625N8)
      in the first half of 2013 on 86 patients in Kashani hospital of Shahrekord.
      Having selected and matched the patients were divided into two groups. Case group
      was dropped tetracaine 0.5% in each of the nasal cavity 15 min before the
      beginning of the operation. The control group was dropped distilled water 15 min
      preoperation in each of the nasal cavity. The surgery lasted about 30-60 min.
      Clinical symptoms were evaluated after anesthetic induction as well as pain using
      the visual analog scale after the operation, in the recovery room. The collected
      data were analyzed using SPSS version software 17 through independent t-test, Chi
      square, and repeated measures variance analysis. Postoperative pain intensity in
      the experimental group compared to the control group was significantly lower than
      the control group (P < 0.05); however, blood pressure and heart rate during
      anesthesia, there was no difference between groups (P > 0.05). Based on the
      findings, intake of tetracaine drop 0.5% has no impact on some hemodynamic
      changes during septoplasty operation. However, compared with the control group,
      pain was significantly reduced.

PMID- 29184842
TI  - The status of Iranian hospital pharmacies according to age-friendly pharmacies
      criteria.
AB  - Due to the increasing elderly population and the subsequent increase in their
      need for medication and more referrals to the pharmacy, this study was conducted
      to investigate the Iranian hospital pharmacies in terms of age-friendliness
      criteria. This was a cross-sectional study conducted in 2017. The study
      population included 3 metropolitan hospital pharmacies selected through clustered
      sampling, and all their 67 pharmacies were included by census. Data collection
      tool was a reliable researcher-made checklist (t = 0.85, alpha = 0.9) Data
      analysis was performed using Kruskal-Wallis test and Mann-Whitney test through
      SPSS version 24. The results in these three cities showed that only two
      pharmacies were in a high level of age-friendly. The relationship between type of
      pharmacy and the final score of age-friendly situation in these cities showed no
      significant relationship. There was no significant relationship among the average
      of the final score of the age-friendly situation in three studied cities. Due to
      the increasing elderly population and the aging society, readiness of Iranian
      hospital pharmacies to provide services to the elderly will be one of the most
      challenging issues in the long term. With proper legislation and policies on
      health-care systems, especially pharmacies, physical and psychological problems
      in elderly can be reduced in the future. Furthermore, with advancing toward age
      friendly pharmacies, the community can be empower and become ready encountering
      elderly problems.

PMID- 29184843
TI  - The performance implications of pharmacy information system at the university
      teaching hospitals of Shiraz, Iran: Cluster approach.
AB  - Pharmacy information system (PIS) is becoming vital in assisting pharmacists to
      do their responsibilities. The aim of this study was to identify the current PIS
      implications in teaching hospitals affiliated with Shiraz University of Medical
      Science. This cross-sectional study was conducted in teaching hospitals
      affiliated with Shiraz University of Medical Science over the year 2016. Data
      were collected by observing the PIS as well as interviewing its users based on
      the researcher-made checklist. The checklist was prepared based on reviewing the
      Persian and English literature and its content validity was approved by the
      experts. To determine the reliability of the checklist, inter-rater reliability
      was used. Data were analyzed using SPSS16, and hospitals were clustered using SK
      means method. In this study, the least conformity to the standards was shown in
      smart clinical features (4.54%), pharmaceutical companies' relationship (32.6%),
      and optimization of drug therapy (34.6%). In contrast, the highest conformity to
      the standards was shown in reporting capabilities (77.3%) and entry information
      and input (70.4%). Medication stock checking and optimization of drug therapy
      were effective features that have made a distinction between hospitals and lead
      to 95% variance between clusters. Based on the results, the current PIS design
      pays less attention to clinical features. Besides, clinical information for
      pharmacists and outside organization relationship were not provided by the
      current system. Thus, emphasis should be placed on the implementation of
      corrective actions to eliminate the current system's deficiencies.

PMID- 29184844
TI  - Effect of different doses of oxytocin on cardiac electrophysiology and
      arrhythmias induced by ischemia.
AB  - The onset of acute myocardial ischemia (MI) is accompanied by a rapid increase in
      electrical instability and often fatal ventricular arrhythmias. This study
      investigated that whether oxytocin (OT) can modulate ischemia-induced arrhythmias
      and considered relationships between the severity of arrhythmia and the
      electrocardiogram parameters during ischemia. OT (0.0001-1 MUg) was administrated
      intraperitoneally 30 min before ischemia. To examine receptor involved, a
      selective OT-receptor antagonist, atosiban (ATO), was infused 10 min before OT.
      OT caused a significant and biphasic dose-dependent reduction in ectopic heart
      activity and arrhythmia score. OT doses that reduced ventricular arrhythmia
      elicited significant increase in QT interval. OT attenuated the
      electrophysiological changes associated with MI and there was significant direct
      relationship between QRS duration and arrhythmia score. ATO treatment reduced
      beneficial effects of OT on arrhythmogenesis. Nevertheless, ATO failed to alter
      OT effects on premature ventricular contractions. We assume that the ability of
      OT to modulate the electrical activity of the heart may play an important role in
      the antiarrhythmic actions of OT.

PMID- 29184845
TI  - The effect of adding ferrous sulfate to methylphenidate on attention
      deficit/hyperactivity disorder in children.
AB  - Attention deficit/hyperactivity disorder (ADHD) is one of the most common
      psychiatric disorders in children with several complications. This study was
      conducted to investigate the effect of adding ferrous sulfate to methylphenidate
      in decreasing ADHD symptoms. This study was a double-blind, randomized clinical
      trial. In this study, 42 nonanemic children with ADHD and serum ferritin below 30
      mg/ml were enrolled according to convenience sampling and randomly assigned to
      two groups of 21 each, cases and controls. The two groups were matched for age
      and sex. The case group was administered with ferrous sulfate 5 mg/kg in addition
      to methylphenidate up to 1 mg/kg and the control group with methylphenidate
      alone. The scores on child symptoms inventory-4 (CSI-4) were recorded at baseline
      and after 2 months of treatment. Data were analyzed by t-test, Pearson's
      correlation coefficient, and repeated measures ANOVA in SPSS 16. The scores on
      CSI-4 decreased significantly at month 2 in both groups (P < 0.001). The scores
      on attention deficit and hyperactivity subscales of the CSI-4 were significantly
      lower in the case group than the control group (P < 0.05). The total score on CSI
      4 decreased more markedly in the case group (P < 0.04). Use of ferrous sulfate
      plus methylphenidate can be effective in reducing ADHD symptoms in nonanemic
      children with low serum ferritin.

PMID- 29184846
TI  - Acacia catechu ethanolic bark extract induces apoptosis in human oral squamous
      carcinoma cells.
AB  - Oral cancer is in approximately 30% of all cancers in India. This study was
      conducted to evaluate the cytotoxic activity of ethanolic extract of Acacia
      catechu bark (ACB) against human squamous cell carcinoma cell line-25 (SCC-25).
      Cytotoxic effect of ACB extract was determined by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium Bromide assay. A. catechu extract was treated SCC-25
      cells with 25 and 50 MUg/mL for 24 h. Apoptosis markers such as caspases-8 and 9,
      bcl-2, bax, and cytochrome c (Cyt-c) were done by RT-PCR. Morphological changes
      of ACB treated cells were evaluated using acridine orange/ethidium bromide
      (AO/EB) dual staining. Nuclear morphology and DNA fragmentation were evaluated
      using propidium iodide (PI) staining. Further, cell cycle analysis was performed
      using flow cytometry. A. catechu treatment caused cytotoxicity in SCC-25 cells
      with an IC50 of 52.09 MUg/mL. Apoptotic marker gene expressions were
      significantly increased on ACB treatment. Staining with AO/EB and PI shows
      membrane blebbing and nuclear membrane distortion, respectively, and it confirms
      the apoptosis induction in SCC-25 cells. These results suggest that ACB extract
      can be used as a modulating agent in oral squamous cell carcinoma.

PMID- 29184847
TI  - Novel biorelevant dissolution medium as a prognostic tool for polysaccharide
      based colon-targeted drug delivery system.
AB  - To overcome the limitations of the conventionally used methods for evaluation of
      orally administered colon-targeted delivery systems, a novel dissolution method
      using probiotics has been recently reported. In the present study, universal
      suitability of this medium composed of five different probiotics is established.
      Different delivery systems - mini tablets, liquisolid compacts, and microspheres
      coated with different polysaccharides - were prepared and subjected to sequential
      dissolution testing in medium with and without microbiota. The results obtained
      from fluid thioglycollate medium (FTM)-based probiotic medium for all the
      polysaccharide-based formulations showed statistically similar dissolution
      profile to that in the rat and goat cecal content media. Hence, it can be
      concluded that the developed FTM-based probiotic medium, once established, may
      eliminate the need for further animal sacrifice in the dissolution testing of
      polysaccharide-based colon-targeted delivery system.

PMID- 29184848
TI  - One- vs. Three-Fraction Pancreatic Stereotactic Body Radiation Therapy for
      Pancreatic Carcinoma: Single Institution Retrospective Review.
AB  - Background/introduction: Early reports of stereotactic body radiation therapy
      (SBRT) for pancreatic ductal adenocarcinoma (PDAC) used single fraction, but
      eventually shifted to multifraction regimens. We conducted a single institution
      review of our patients treated with single- or multifraction SBRT to determine
      whether any outcome differences existed. Methods and materials: Patients treated
      with SBRT in any setting for PDAC at our facility were included, from 2004 to
      2014. Overall survival (OS), local control (LC), regional control (RC), distant
      metastasis (DM), and late grade 3 or greater radiation toxicities from the time
      of SBRT were calculated using Kaplan-Meier estimation to either the date of last
      follow-up/death or local/regional/distant failure. Results: We identified 289
      patients (291 lesions) with pathologically confirmed PDAC. Median age was 69
      (range, 33-90) years. Median gross tumor volume was 12.3 (8.6-21.3) cm3 and
      planning target volume 17.9 (12-27) cm3. Single fraction was used in 90 (30.9%)
      and multifraction in 201 (69.1%) lesions. At a median follow-up of 17.3 months
      (IQR 10.1-29.3 months), the median survival for the entire cohort 17.8 months
      with a 2-year OS of 35.3%. Univariate analysis showed multifraction schemes to
      have a higher 2-year OS 30.5% vs. 37.5% (p = 0.019), it did not hold significance
      on MVA. Multifractionation schemes were found to have a higher LC on MVA (HR =
      0.53, 95% CI, 0.33-0.85, p = 0.009). At 2 years, late grade 3+ toxicity was 2.5%.
      Post-SBRT CA19-9 was found on MVA to be a prognostic factor for OS (HR = 1.01,
      95% CI, 1.01-1.01, p = 0.009), RC (HR = 1.01, 95% CI 1.01-1.01, p = 0.02), and DM
      (HR = 1.01, 95% CI, 1.01-1.01, p = 0.001). Conclusion: Our single institution
      retrospective review is the largest to date comparing single and multifraction
      SBRT and the first to show multifraction regimen SBRT to have a higher LC than
      single fractionation. Additionally, we show low rates of severe late toxicity
      with SBRT.

PMID- 29184849
TI  - Giving Drugs a Second Chance: Overcoming Regulatory and Financial Hurdles in
      Repurposing Approved Drugs As Cancer Therapeutics.
AB  - The repositioning or "repurposing" of existing therapies for alternative disease
      indications is an attractive approach that can save significant investments of
      time and money during drug development. For cancer indications, the primary goal
      of repurposed therapies is on efficacy, with less restriction on safety due to
      the immediate need to treat this patient population. This report provides a high
      level overview of how drug developers pursuing repurposed assets have previously
      navigated funding efforts, regulatory affairs, and intellectual property laws to
      commercialize these "new" medicines in oncology. This article provides insight
      into funding programs (e.g., government grants and philanthropic organizations)
      that academic and corporate initiatives can leverage to repurpose drugs for
      cancer. In addition, we highlight previous examples where secondary uses of
      existing, Food and Drug Administration- or European Medicines Agency-approved
      therapies have been predicted in silico and successfully validated in vitro
      and/or in vivo (i.e., animal models and human clinical trials) for certain
      oncology indications. Finally, we describe the strategies that the pharmaceutical
      industry has previously employed to navigate regulatory considerations and
      successfully commercialize their drug products. These factors must be carefully
      considered when repurposing existing drugs for cancer to best benefit patients
      and drug developers alike.

PMID- 29184850
TI  - Internalization of the Active Subunit of the Aggregatibacter
      actinomycetemcomitans Cytolethal Distending Toxin Is Dependent upon Cellugyrin
      (Synaptogyrin 2), a Host Cell Non-Neuronal Paralog of the Synaptic Vesicle
      Protein, Synaptogyrin 1.
AB  - The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is a
      heterotrimeric AB2 toxin capable of inducing lymphocytes, and other cell types,
      to undergo cell cycle arrest and apoptosis. Exposure to Cdt results in binding to
      the cell surface followed by internalization and translocation of the active
      subunit, CdtB, to intracellular compartments. These events are dependent upon
      toxin binding to cholesterol in the context of lipid rich membrane microdomains
      often referred to as lipid rafts. We now demonstrate that, in addition to binding
      to the plasma membrane of lymphocytes, another early and critical event initiated
      by Cdt is the translocation of the host cell protein, cellugyrin (synaptogyrin-2)
      to the same cholesterol-rich microdomains. Furthermore, we demonstrate that
      cellugyrin is an intracellular binding partner for CdtB as demonstrated by
      immunoprecipitation. Using CRISPR/cas9 gene editing we established a Jurkat cell
      line deficient in cellugyrin expression (JurkatCg-); these cells were capable of
      binding Cdt, but unable to internalize CdtB. Furthermore, JurkatCg- cells were
      not susceptible to Cdt-induced toxicity; these cells failed to exhibit blockade
      of the PI-3K signaling pathway, cell cycle arrest or cell death. We propose that
      cellugyrin plays a critical role in the internalization and translocation of CdtB
      to critical intracellular target sites. These studies provide critical new
      insight into the mechanism by which Cdt, and in particular, CdtB is able to
      induce toxicity.

PMID- 29184851
TI  - Bid-Induced Release of AIF/EndoG from Mitochondria Causes Apoptosis of
      Macrophages during Infection with Leptospira interrogans.
AB  - Leptospirosis is a global zoonotic infectious disease caused by pathogenic
      Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL
      caspase-8/3 pathway plays an important role in the survival and proliferation of
      the pathogen in hosts. Although, the release of mitochondrial apoptosis-inducing
      factor (AIF) and endonuclease G (EndoG) in leptospire-infected macrophages has
      been described, the mechanisms linking caspase and mitochondrion-related host
      cell apoptosis has not been determined. Here, we demonstrated that leptospire
      infection induced apoptosis through mitochondrial damages in macrophages.
      Apoptosis was caused by the mitochondrial release and nuclear translocation of
      AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the
      mitochondrion-related CytC-caspase-9/3 pathway was not activated. Next, we found
      that the release and translocation of AIF and/or EndoG was preceded by the
      activation of the BH3-interacting domain death agonist (Bid). Furthermore, our
      data demonstrated that caspase-8 was activated during the infection and caused
      the activation of Bid. Meanwhile, high reactive oxygen species (ROS) trigged by
      the infection caused the dephosphorylation of Akt, which also activated Bid. In
      conclusion, Bid-mediated mitochondrial release of AIF and/or EndoG followed by
      nuclear translocation is a major mechanism of leptospire- induced apoptosis in
      macrophages, and this process is modulated by both caspase-8 and ROS-Akt signal
      pathways.

PMID- 29184852
TI  - A New Determinant of Candida glabrata Virulence: The Acetate Exporter CgDtr1.
AB  - Persistence and virulence of Candida glabrata infections are multifactorial
      phenomena, whose understanding is crucial to design more suitable therapeutic
      strategies. In this study, the putative multidrug transporter CgDtr1, encoded by
      ORF CAGL0M06281g, is identified as a determinant of C. glabrata virulence in the
      infection model Galleria mellonella. CgDTR1 deletion is shown to decrease the
      ability to kill G. mellonella larvae by decreasing C. glabrata ability to
      proliferate in G. mellonella hemolymph, and to tolerate the action of hemocytes.
      The possible role of CgDtr1 in the resistance to several stress factors that
      underlie death induced by phagocytosis was assessed. CgDTR1 was found to confer
      resistance to oxidative and acetic acid stress. Consistently, CgDtr1 was found to
      be a plasma membrane acetic acid exporter, relieving the stress induced upon C.
      glabrata cells within hemocytes, and thus enabling increased proliferation and
      virulence against G. mellonella larvae.

PMID- 29184853
TI  - Porphyromonas gingivalis-Derived Lipopolysaccharide Combines Hypoxia to Induce
      Caspase-1 Activation in Periodontitis.
AB  - Periodontitis is defined as inflammation affecting the supporting tissue of
      teeth. Periodontal pathogens initiate the disease and induce inflammatory host
      response. Hypoxia may accelerate the process by producing pro-inflammatory
      factors. The aim of this study is to investigate the effect of Porphyromonas
      gingivalis (P. gingivalis) lipopolysaccharides (LPS) and Escherichia coli (E.
      coli) LPS in inducing caspase-1 activation in normoxic or hypoxic phases. The
      results showed that healthy gingiva was in a normoxic phase (HIF-1alpha
      negative). However, hypoxia appeared in periodontitis, in which NLRP3, cleaved
      caspase-1, interleukin 1 beta (IL-1beta) and caspase-1-induced cell death was
      enhanced in periodontitis specimens. The in vitro experiment showed that P.
      gingivalis LPS slightly decreased the level of NLRP3 and IL-1beta in gingival
      fibroblasts under normoxia. Surprisingly, hypoxia reversed the effects of P.
      gingivalis LPS, highly promoted caspase-1 activation and IL-1beta maturation. E.
      coli LPS, a kind of pathogen-associated molecular pattern (PAMP) was chosen to
      simulate the effect of Gram-negative microbiota. Different from P. gingivalis
      LPS, E. coli LPS enhanced IL-1beta maturation both in normoxia and hypoxia.
      Moreover, E. coli LPS turned normoxia into hypoxia phase in experimental
      periodontitis model, which may subsequently propel the inflammatory effect of P.
      gingivalis LPS. It was concluded that E. coli LPS induced a hypoxic phase, which
      is a combing pathological factor of P. gingivalis LPS in caspase-1 activating and
      IL-1beta maturation in periodontal inflammation.

PMID- 29184855
TI  - Dealing with complex overactive bladder syndrome patient profiles with focus on
      fesoterodine: in or out of the EAU guidelines?
AB  - Overactive bladder (OAB) syndrome is a common, complex, and challenging
      condition. To assist the management of these patients, the European Association
      of Urology (EAU) updates its guidelines annually. This review reports the
      presentations from the symposium titled "Dealing with complex OAB patient
      profiles: in or out of the EAU guidelines?" held at the 32nd EAU Annual Congress
      in March 2017 in London. The symposium focused on three groups of OAB patients:
      women who may also suffer pelvic organ prolapse, stress urinary incontinence, the
      genitourinary syndrome of menopause (GSM); patients at risk of cognitive
      impairment; and elderly patients. The aim of the symposium was to determine how
      the 2017 EAU guidelines can best assist physicians, as well as to assess the
      benefits of fesoterodine in these patients. The EAU guidelines recommend
      antimuscarinic agents (grade A) for the medical treatment of OAB. In women, OAB
      is correlated with GSM, both of which are underdiagnosed and undertreated.
      Fesoterodine decreases OAB symptoms and the associated limitation of physical
      activity. A combination of fesoterodine and vaginal estrogens is appropriate for
      OAB associated with GSM. In patients at risk of cognitive impairment, prescribers
      should pay particular attention to the choice of medication. Fesoterodine is a
      Pgp substrate with limited ability to cross the blood-brain barrier, which may
      explain the lack of negative effects on the central nervous system observed in
      clinical trials of this agent. OAB should not be regarded as a normal consequence
      of aging. Fesoterodine has been extensively investigated in the elderly, and is
      the only anticholinergic drug licensed for OAB in this population, rated B
      (beneficial) according to the Fit for the Aged classification for lower-urinary
      tract symptoms. The EAU guidelines are a valuable resource for physicians
      managing patients with OAB, and the pharmacological properties of fesoterodine
      offer credible clinical advantages in these three patient groups.

PMID- 29184854
TI  - Oncolytic virus delivery: from nano-pharmacodynamics to enhanced oncolytic
      effect.
AB  - With the advancement of a growing number of oncolytic viruses (OVs) to clinical
      development, drug delivery is becoming an important barrier to overcome for
      optimal therapeutic benefits. Host immunity, tumor microenvironment and abnormal
      vascularity contribute to inefficient vector delivery. A number of novel
      approaches for enhanced OV delivery are under evaluation, including use of
      nanoparticles, immunomodulatory agents and complex viral-particle ligands along
      with manipulations of the tumor microenvironment. This field of OV delivery has
      quickly evolved to bioengineering of complex nanoparticles that could be
      deposited within the tumor using minimal invasive image-guided delivery. Some of
      the strategies include ultrasound (US)-mediated cavitation-enhanced
      extravasation, magnetic viral complexes delivery, image-guided infusions with
      focused US and targeting photodynamic virotherapy. In addition, strategies that
      modulate tumor microenvironment to decrease extracellular matrix deposition and
      increase viral propagation are being used to improve tumor penetration by OVs.
      Some involve modification of the viral genome to enhance their tumoral
      penetration potential. Here, we highlight the barriers to oncolytic viral
      delivery, and discuss the challenges to improving it and the perspectives of
      establishing new modes of active delivery to achieve enhanced oncolytic effects.

PMID- 29184856
TI  - Optimal therapy for patients with hepatocellular carcinoma and resistance or
      intolerance to sorafenib: challenges and solutions.
AB  - The only US Food and Drug Administration (FDA)-approved first-line systemic
      therapy for hepatocellular carcinoma (HCC) is sorafenib; however, resistance or
      intolerance to sorafenib is unfortunately common. In this review, we briefly
      describe systemic therapies that can be considered for patients with HCC who show
      resistance or intolerance to sorafenib. For all patients with HCC who need
      systemic therapy, we strongly advocate for participation in clinical trials.
      Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with
      some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and
      oxaliplatin) and GEMOX (gemcitabine-oxaliplatin). Multi-target kinase inhibitors
      such as lenvantinib and regorafenib have recently met their primary endpoints as
      first- and second-line therapy, respectively, with regorafenib now representing
      the only FDA-approved drug for second-line treatment of HCC. Other targeted
      therapies remain under investigation, but results so far have not significantly
      changed clinical practice. Immunotherapy is an interesting area of research in
      the treatment of HCC with preclinical and early clinical data demonstrating
      exciting results; thus numerous investigational studies are currently focusing on
      immunotherapy in the treatment of HCC. While systemic treatment options in HCC
      remain a challenge for providers, in this review, we summarize the current
      literature and highlight areas of progress with respect to the treatment of
      patients with HCC and resistance or intolerance to sorafenib.

PMID- 29184857
TI  - Vacuum extraction vaginal delivery: current trend and safety.
AB  - Operative vaginal birth retains an important role in current obstetric practice.
      However, there is an increasing trend in the rate of cesarean section in Korea.
      Surgical delivery is more advantageous than cesarean section, but the rate of
      operative vaginal delivery is decreasing for various reasons. Furthermore, there
      is no unified technique for vacuum extraction delivery. In this context, this
      review was performed to provide details of the necessary conditions, techniques,
      benefits, and risks of operative vaginal delivery. Future research should focus
      on overcoming the limitations of operative vaginal delivery.

PMID- 29184858
TI  - What is fetal programming?: a lifetime health is under the control of in utero
      health.
AB  - The "Barker hypothesis" postulates that a number of organ structures and
      associated functions undergo programming during embryonic and fetal life, which
      determines the set point of physiological and metabolic responses that carry into
      adulthood. Hence, any stimulus or insult at a critical period of embryonic and
      fetal development can result in developmental adaptations that produce permanent
      structural, physiological and metabolic changes, thereby predisposing an
      individual to cardiovascular, metabolic and endocrine disease in adult life. This
      article will provide evidence linking these diseases to fetal undernutrition and
      an overview of previous studies in this area as well as current advances in
      understanding the mechanism and the role of the placenta in fetal programming.

PMID- 29184859
TI  - Risk factors for massive postpartum bleeding in pregnancies in which incomplete
      placenta previa are located on the posterior uterine wall.
AB  - Objective: To identify factors associated with massive postpartum bleeding in
      pregnancies complicated by incomplete placenta previa located on the posterior
      uterine wall. Methods: A retrospective case-control study was performed. We
      identified 210 healthy singleton pregnancies with incomplete placenta previa
      located on the posterior uterine wall, who underwent elective or emergency
      cesarean section after 24 weeks of gestation between January 2006 and April 2016.
      The cases with intraoperative blood loss (>=2,000 mL) or transfusion of packed
      red blood cells (>=4) or uterine artery embolization or hysterectomy were defined
      as massive bleeding. Results: Twenty-three women experienced postpartum profuse
      bleeding (11.0%). After multivariable analysis, 4 variables were associated with
      massive postpartum hemorrhage (PPH): experience of 2 or more prior uterine
      curettage (adjusted odds ratio [aOR], 4.47; 95% confidence interval [CI], 1.29 to
      15.48; P=0.018), short cervical length before delivery (<2.0 cm) (aOR, 7.13; 95%
      CI, 1.01 to 50.25; P=0.049), fetal non-cephalic presentation (aOR, 12.48; 95% CI,
      1.29 to 121.24; P=0.030), and uteroplacental hypervascularity (aOR, 6.23; 95% CI,
      2.30 to 8.83; P=0.001). Conclusion: This is the first study of cases with
      incomplete placenta previa located on the posterior uterine wall, which were
      complicated by massive PPH. Our findings might be helpful to guide obstetric
      management and provide useful information for prediction of massive PPH in
      pregnancies with incomplete placenta previa located on the posterior uterine
      wall.

PMID- 29184860
TI  - Safety of umbilical cord milking in very preterm neonates: a randomized
      controlled study.
AB  - Objective: To investigate the safety of umbilical cord milking on both the mother
      and neonate among very preterm deliveries of less than 33 weeks of gestation.
      Methods: Pregnant women who were expected to deliver at between 24 0/7 and 32 6/7
      weeks of gestation were randomized to either the umbilical cord milking or
      immediate cord clamping group. Maternal and neonatal data associated with
      delivery, in addition to neonatal morbidity and mortality data, were collected
      and analyzed. Results: Of the 66 preterm deliveries included in the study, 34
      were randomized into the milking and 32 into the clamping group. Differences
      between maternal pre- and post-partum hemoglobin levels were 1.35 g/dL in the
      milking and 1.58 g/dL in the clamping group (P=0.451). Neonatal Apgar scores at
      both 1 and 5 minutes, initial blood gas analysis results, body temperature at
      admission, need for early intubation, and maximum bilirubin levels were all
      similar between the 2 groups. However, neonatal hemoglobin levels at birth (15.79
      vs. 14.69 g/dL; P<0.05) and at 24 hours of age (14.83 vs. 13.29 g/dL; P<0.05)
      were significantly higher in the milking group. Neonates in the clamping group
      required more blood transfusion (1.78 vs. 0.93; P=0.049), and a higher percentage
      of neonates in the clamping group required inotropic drugs (63% vs. 29%;
      P=0.007). The mortality rate was significantly lower in the milking group (6% vs.
      28%; P=0.015). Conclusion: Umbilical cord milking can be a safe and beneficial
      procedure for both the mother and the neonate in deliveries of less than 33 weeks
      of gestation.

PMID- 29184861
TI  - Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux in
      women at risk after cesarean section.
AB  - Objectives: Cesarean section is associated with an increased risk for venous
      thromboembolism (VTE). The safety and efficacy of primary prophylaxis of
      fondaparinux, a synthetic sulfated pentasaccharide heparin analog, in women at
      risk after cesarean section is uncertain. Methods: This was a retrospective study
      of 295 cases of pregnant women presenting to a tertiary referral center of Nara,
      Japan, to evaluate the usefulness of thromboprophylaxis with fondaparinux after
      cesarean delivery between 2011 and 2012. Patients were initially received
      unfractionated heparin (once 5,000 IU subcutaneously, twice a day), starting 6
      hours after cesarean section for 24 hours, and then treated with fondaparinux
      (once 2.5 mg daily, subcutaneously) for 5 days. The primary efficacy end-point
      was an improvement in the incidence of symptomatic VTE or fatal post-cesarean
      pulmonary thromboembolism. The primary safety end-point was major bleeding during
      treatment. Results: There were neither any episodes of symptomatic VTE cases nor
      maternal deaths. A total of 10 patients had a bleeding event. Major bleeding
      complication was observed in 2 (0.68%) of 295 patients receiving fondaparinux.
      Non-major bleeding into critical sites was observed in 8 patients, often at
      surgical sites, and recovery was not delayed. Conclusion: This study demonstrates
      the safety and efficacy of fondaparinux in women at high risk of VTE after
      cesarean section. Large phase trials comparing clinical outcomes with
      fondaparinux across a wide spectrum of patients are needed to confirm these
      observations.

PMID- 29184863
TI  - A retrospective comparison of outcome in IB2 and IIA cervical cancer patients
      treated with primary concurrent chemoradiation versus radical hysterectomy with
      or without tailored adjuvant therapy.
AB  - Objective: The aim of our study is to compare the overall survival (OS),
      progression-free survival (PFS), and treatment-related morbidities between
      primary concurrent chemoradiation therapy (CCRT) vs. radical hysterectomy (RH)
      with or without tailored adjuvant therapy in patients with stages IB2 and IIA
      cervical cancer. Methods: This was a retrospective study of 113 patients with IB2
      or IIA cervical cancer treated with either primary CCRT (n=49) or RH (n=64) with
      or without tailored adjuvant therapy between 2002 and 2011 at Keimyung University
      Dongsan Medical Center. Patients in RH group was divided into those undergoing
      surgery alone (n=26) and those undergoing surgery with adjuvant therapy (n=38).
      Results: The median follow up period was 66 months. The 5-year OS by treatment
      modality was 88.7% for the 64 patients in the RH group and 72.8% for 49 patients
      in the CCRT group (P=0.044). The 5-year PFS was 82.3% and 65.6% after RH group
      and CCRT group (P=0.048), respectively. Grade 3-4 complication was less frequent
      after RH alone (7.7%) than RH with adjuvant therapy (34.2%) or CCRT group (28.6%)
      (P=0.047). Conclusion: The RH group seems to be superior to the CCRT group in
      oncologic outcomes. However, considering the selection bias including tumor size,
      lymph node meta, and parametrial invasion in pretreatment magnetic resonance
      imaging, both treatment modalities are reasonable and feasible in cervical cancer
      IB2 and IIA. It is important to choose the appropriate treatment modality
      considering the age and general condition of the patient. Randomized controlled
      study is needed to confirm the result of our study and determine the optimal
      treatment.

PMID- 29184862
TI  - The clinical significance of D-dimer concentrations in patients with gestational
      hypertensive disorders according to the severity.
AB  - Objective: Pregnancy is a major risk factor of thromboembolism, and the patients
      with preeclampsia (PE) are known to have higher risk of thromboembolic
      complications than normal pregnant women. D-dimer is a well-established
      laboratory marker for the screening of venous thromboembolism (VTE), but the
      concentrations of d-dimer tend to increase physiologically in pregnant women
      throughout the gestational age. We performed this study to evaluate the clinical
      significance of d-dimer concentrations in patients with gestational hypertensive
      disorders (GHD) according to the severity. Methods: Retrospective cohort study
      was performed in one institution. Singleton pregnant women with GHD were
      enrolled, and their antepartum concentrations of d-dimer were measured as a part
      of routine evaluation for patients suspected with PE. Patients with multiple
      gestations, rheumatic diseases, autoimmune diseases, or suspected VTE were
      excluded. A categorization of severity about PE was based on the general
      criteria. Results: In 73.3% of study population, their d-dimer concentrations
      exceeded the normal range (>0.55 mg/L). A significantly greater proportion of
      pregnant women had excessive concentrations of d-dimer in the severe GHD than in
      the non-severe GHD (89.8% vs. 53.7%; P<0.01). Patients with severe GHD had
      significantly higher median concentrations of d-dimer than those with non-severe
      GHD (median [range], 2.00 mg/L [0.11 to 7.49] vs. 0.71 mg/L [0.09 to 5.39];
      P<0.01) although their earlier gestational ages of sampling. Conclusion: Maternal
      concentrations of d-dimer were significantly elevated in patients with severe
      features than those without severe features among those with GHD. Some pregnant
      women with GHD can have markedly elevated concentrations of d-dimer without any
      evidence of current VTE.

PMID- 29184864
TI  - Prognostic value of preoperative lymphocyte-monocyte ratio in elderly patients
      with advanced epithelial ovarian cancer.
AB  - Objective: To investigate the prognostic significance of preoperative lymphocyte
      monocyte ratio (LMR) in elderly patients with advanced epithelial ovarian cancer
      (EOC) receiving primary cytoreductive surgery and adjuvant platinum-based
      chemotherapy. Methods: A total of 42 elderly patients (>=65 years) diagnosed with
      EOC who are receiving primary cytoreductive surgery and adjuvant platinum-based
      chemotherapy from 2009 to 2012 was included. LMR was calculated from complete
      blood cell count sampled before operation. Receiver operating characteristic
      (ROC) curves were used to calculate optimal cut-off values for LMR. Prognostic
      significance with respect to overall survival (OS) and progression-free survival
      (PFS) were determined using log-rank test and Cox regression analysis. Results:
      The optimized LMR cut-off value determined by ROC curve analysis was 3.63 for PFS
      and OS. The high LMR group (LMR >=3.63) was found to be significantly more
      associated with optimal debulking (P=0.045) and platinum response (P=0.018) than
      the low LMR group. In addition, Kaplan-Meier analysis revealed the LMR-high group
      was significantly more associated with high PFS and OS rates (P=0.023 and
      P=0.033, respectively), and univariate analysis revealed that a high LMR,
      histology type, and optimal debulking and platinum responses were significantly
      associated with prolonged PFS and OS. However, subsequent Cox multivariate
      analysis showed only optimal debulking and platinum response were independent
      prognostic factors of PFS or OS. Conclusion: This study suggests that LMR might
      be associated with treatment and survival outcomes in elderly patients with EOC
      receiving standard oncology treatment.

PMID- 29184865
TI  - Etiological evaluation of repeated biochemical pregnancy in infertile couples who
      have undergone in vitro fertilization.
AB  - Objective: This study aims to investigate whether there are any notable
      etiologies for repeated biochemical pregnancy (RBP) and, if so, to compare those
      etiologies associated with repeated spontaneous abortion in infertile couples who
      have undergone in vitro fertilization (IVF). Methods: Forty-four infertile
      couples who underwent IVF and experienced RBP were included in this study. RBP
      was defined as more than 2 early pregnancy losses that occurred before the
      detection of a gestational sac, with ectopic pregnancies specifically excluded by
      serial serum beta human chorionic gonadotropin evaluation. Forty-three infertile
      couples who underwent IVF and experienced recurrent spontaneous abortion (RSA)
      were included as a control group. Karyotype analysis, anatomic evaluation of
      uterus, endocrine and immunological evaluation were performed. In addition, the
      number of pregnant women confirmed by 12 weeks' gestation was compared between
      groups. Results: Immunological factors (RSA: 20.9% vs. RBP: 29.5%, P=0.361),
      diminished ovarian reserve (RSA: 10.9% vs. RBP: 17%, P=0.552), and parental
      chromosomal abnormalities (RSA: 18.6% vs. RBP: 9.1%, P=0.218) were not different
      between groups. Additionally, the incidence of uterine factors (RSA: 11.6% vs.
      RBP: 4.6%, P=0.206), unknown cause (RSA: 48.8% vs. RBP: 54.5%, P=0.161), and the
      pregnancy outcome identified until 12 weeks' gestation (RSA: 46.5% vs. RBP:
      38.6%, P=0.520) did not differ between groups. Conclusion: In the present study,
      the causes of RBP after IVF were similar to those of RSA. Accordingly, we suggest
      that efforts should be made to define the etiology of RBP, particularly for
      infertile couples, and that possible management strategies should be offered.

PMID- 29184866
TI  - Therapeutic outcomes of methotrexate injection in unruptured interstitial
      pregnancy.
AB  - Objective: To examine the therapeutic outcomes of methotrexate (MTX) in the
      treatment of unruptured interstitial pregnancy. Methods: We reviewed the medical
      records of patients who were diagnosed with interstitial pregnancy and received
      MTX as first-line treatment between January 2003 and July 2014 at CHA Gangnam
      Medical Center. The treatment success rates and subsequent pregnancy outcomes
      were examined. Results: Ninety-seven patients were diagnosed with interstitial
      pregnancy between January 2003 and July 2014. Of them, 38 initially received MTX
      treatment. The diagnosis was made at a median of 6+3 weeks (5+0 to 11+3 weeks).
      Thirty patients received a systemic MTX injection, while the other 8 received a
      local MTX injection. Systemic treatment composed of an 8-day alternating MTX
      regimen, single-dose regimen, or high-dose regimen (100 mg/m2 + 200 mg/m2
      intravenously over 12 hours). The local injection consisted of a direct MTX
      injection into the gestational sac with or without systemic MTX injection. Twenty
      one patients (55.3%) were successfully treated with MTX. However, MTX therapy
      failed in 17 patients (44.7%), who required surgery. Mode of MTX treatment was
      the only predictive variable of MTX treatment success (P=0.039). Treatment
      success was seen in 7 of 8 patients (87.5%) in the local MTX group vs. 14 of 30
      patients (46.7%) in the systemic MTX group. After treatment, 13 patients
      attempted a successive pregnancy; of them, 10 patients had a confirmed clinical
      pregnancy and healthy live birth. Conclusion: Combined MTX treatment including a
      local injection might be an initial approach to the treatment of interstitial
      pregnancy.

PMID- 29184867
TI  - Comorbidity of gynecological and non-gynecological diseases with adenomyosis and
      endometriosis.
AB  - Objective: Adenomyosis and endometriosis are relatively common gynecological
      diseases that exhibit many common features. This study identified gynecological
      and non-gynecological diseases that exhibited comorbidity with adenomyosis and
      endometriosis in Korean women. Methods: We used Health Insurance Review and
      Assessment data from 2009 to 2011 and searched for adenomyosis and endometriosis
      (coded as N80.1 and D25 in International Classification of Disease, 10th revision
      [ICD-10], respectively). We selected records from patients who had independent
      disease occurrences in each year, and comorbidities were estimated using Fisher's
      exact test. We computed each year's similarities and combined 3 years' results
      using Fisher's P-value summation method. Results: A total of 61,516 patients'
      data were collected during the study period. The prevalence of adenomyosis and
      endometriosis were similar each year: 12.4% and 9.3% in 2009, 12.5% and 9.4% in
      2010 and 13.3% and 9.1% in 2011, respectively. Meta-analysis revealed that 31 ICD
      10 codes were significantly related with adenomyosis, and 44 ICD-10 codes were
      related with endometriosis. Gynecological diseases, such as leiomyoma and benign
      ovarian tumor, were significantly related to adenomyosis and endometriosis. Non
      gynecological diseases, such as anemia and hypercholesterolemia, were also
      related to adenomyosis and endometriosis. Conclusion: We must monitor for the
      presence of gynecological and non-gynecological diseases with co-morbidities
      during evaluations and follow-up of patients with adenomyosis or endometriosis.

PMID- 29184868
TI  - Long-term recurrence-free survival of a patient with advanced pure primary
      ovarian squamous cell carcinoma treated with dose-dense paclitaxel combined with
      carboplatin.
AB  - We describe an extremely rare case of advanced pure primary ovarian squamous cell
      carcinoma (SCC), treated by adjuvant chemotherapy with dose-dense paclitaxel
      combined with carboplatin (dd-TC) plus the combination chemotherapy with
      irinotecan and cisplatin (CPT-P), with long-term recurrence-free survival. A 71
      year-old woman complaining of lower abdominal pain was referred to our hospital
      and a 7-cm-diameter solid tumor was identified. She was diagnosed with a left
      ovarian tumor that was highly suspicious for malignancy based on ultrasonography,
      magnetic resonance imaging, and contrast-enhanced computed tomography. Bilateral
      salpingo-oophorectomy, low-anterior colon resection, and colostomy were
      performed. Intra- and post-operative histopathological diagnosis revealed
      International Federation of Gynecology and Obstetrics stage IIIc well
      differentiated pure ovarian SCC. As adjuvant chemotherapy, 2 courses of dd-TC
      were administered, followed by 3 courses of CPT-P; the patient then underwent 4
      additional courses of dd-TC. Both regimens were effective and there has been no
      recurrence or metastasis thus far in the 5 years since the operation.

PMID- 29184869
TI  - Skin metastases in ovarian clear cell adenocarcinoma: a case report and a review
      of the literature.
AB  - Epithelial ovarian carcinoma is a high mortality neoplasm in gynecologic
      malignancy. It usually can metastasize to distant organs such as pleura, liver,
      lung, and lymph nodes. However, the skin metastases are not common and related to
      very poor prognosis. Here we report a 54-year-old patient with ovarian clear cell
      carcinoma with skin metastases on the anterior chest at 11 months after initial
      diagnosis. Although she received palliative chemotherapy, she expired due to
      disease progression 2 months later after the diagnosis of skin metastases.

PMID- 29184870
TI  - A retroperitoneal dedifferentiated liposarcoma mimicking an ovarian tumor.
AB  - A 74-year-old postmenopausal woman visited our gynecology clinic complaining of a
      palpable abdominal mass. Physical and radiological evaluation indicated that the
      mass exhibited features of a left ovarian neoplasm showing heterogeneous
      enhancement. Surgical resection was performed to confirm this suspicion. During
      surgery, a mass was observed only in the left ovary with no invasive growth, but
      adhesions to the surrounding peritoneum were seen. Given the patient's age, large
      mass size, and accompanying uterine myoma and right ovarian cyst, total abdominal
      hysterectomy with bilateral salpingo-oophorectomy was performed. The final
      pathologic diagnosis was dedifferentiated liposarcoma. The liposarcoma was
      suspected to originate from retroperitoneal adipose tissue rather than the ovary.
      Radiotherapy was planned if a gross lesion indicating recurrence followed 6
      months later. This case required a considerable multi-disciplinary approach for
      diagnosis and treatment because of its ambiguous clinical and radiological
      findings.

PMID- 29184871
TI  - Peptide YY producing strumal carcinoid tumor of the ovary in a postmenopausal
      woman: a rare cause of chronic constipation.
AB  - Strumal carcinoid tumor of the ovary is a rare subtype of ovarian carcinoid
      tumors; it is characterized by an intimate mixture of thyroid and carcinoid
      tissues. We present a case of a 64-year-old woman who presented with the chief
      complaint of persistent, severe constipation for over 5 years; she was later
      found to have an ovarian strumal carcinoid tumor. Computed tomography showed a
      well-defined solid mass measuring 6.4 cm at the right adnexa. The patient
      underwent right salpingo-oophorectomy and was histopathologically diagnosed as
      having a strumal carcinoid tumor. Immunohistochemical examination showed
      immunoreactivity for peptide YY (PYY), which exerts an inhibitory effect on the
      peristaltic actions of the distal intestine. After surgery, the patient's
      constipation resolved rapidly, suggesting a correlation between PYY producing
      ovarian carcinoid tumor and constipation. This is the first case report of PYY
      producing primary strumal carcinoid tumor of the ovary associated with
      persistent, severe constipation from Korea.

PMID- 29184873
TI  - Two cases of hymenal scars occurred by child rape.
AB  - Children who have been raped some years back may have hymenal scars. However,
      medical professionals are not accustomed in assessing these scars because of the
      lack of experience in performing physical examinations of the external genitalia
      of children who suffered from rape some years back. Moreover, the importance of
      physical examination of the victim's external genitalia is sometimes overlooked.
      Two cases of rape victims with hymenal scars who visited Daegu Child Sexual Abuse
      Response Center several years after their first sexual abuse along with a
      literature review are presented here.

PMID- 29184872
TI  - Laparoscopic total extraperitoneal hernia repair of fallopian tube indirect
      inguinal hernia in reproductive aged woman: a case report.
AB  - An indirect inguinal hernia containing the fallopian tube alone is extremely rare
      in reproductive-aged women without any genital tract anomalies. Despite this
      rarity, early diagnosis and adequate management is important to prevent
      strangulation and recurrence. We present a case of an indirect inguinal hernia
      containing only the fallopian tube in the hernia sac, which was successfully
      reduced by using a laparoscopic total extraperitoneal approach and repaired with
      a polypropylene mesh.

PMID- 29184874
TI  - Persistent low-level elevation of serum human chorionic gonadotropin after
      termination of pregnancy: a rare case of peritoneal trophoblastic implant.
AB  - Peritoneal trophoblastic implant can occur after treatment of ectopic pregnancy.
      Similarly, after termination of intrauterine pregnancy, trophoblastic implants
      are rare but can be a complication of perforation during dilatation and
      curettage. We report an extremely rare case of trophoblastic implant on the
      myometrium, ovarian surface, and peritoneal wall 4 months after uncomplicated
      dilatation and curettage. To the best of our knowledge, this is the first case of
      peritoneal trophoblastic implant following dilatation and curettage without
      uterine perforation. Knowledge of this case is useful for the management of
      patients with persistent low-level elevation of serum human chorionic
      gonadotropin after termination of pregnancy.

PMID- 29184875
TI  - Assessing cosmetic results after conventional thyroidectomy using the EASY-EYE_C:
      a double-blind randomized controlled trial.
AB  - Purpose: The incidence of thyroid cancer is relatively high, especially in young
      women, and postoperative scarring after thyroidectomy is an important problem for
      both patients and clinicians. Currently, there is no available product that can
      be used for wound protection during thyroid surgery. We used the EASY-EYE_C, a
      new silicone-based wound protector. Methods: We conducted a double-blind
      randomized controlled trial to assess the efficacy of the EASY-EYE_C with
      surgical scars. We studied 66 patients who underwent conventional total
      thyroidectomy or hemithyroidectomy performed by a single surgeon from August 2015
      to June 2016. At 6-week follow-up, a single blinded physician observed the wounds
      to make clinical assessments using the Patient and Observer Scar Assessment Scale
      (POSAS), the Vancouver Scar Scale (VSS), and a modified Stony Brook Scar
      Evaluation Scale (SBSES). Results: There were no significant differences by sex,
      age, type of surgery, body mass index, length of wound, incision site (from
      sternal notch), or thyroid weight, but the duration of operation was
      significantly shorter in the experimental group (E group). The e-group also had
      better POSAS scores than the control group (C group), with means of 43.2
      (standard deviation [SD], +/-15.9) versus 68.3 (SD, +/-21.5), respectively (P <
      0.05). The modified SBSES and VSS scores were similar to those from the POSAS.
      Conclusion: In this study, all scores for evaluating outcomes were higher in the
      E group than in the C group. In addition, the operation time was significantly
      shorter in the E group. Therefore, the EASY-EYE_C may be useful for improving the
      cosmetic outcomes of conventional thyroid surgery.

PMID- 29184876
TI  - Feasibility of sentinel lymph node dissection using Tc-99m phytate in papillary
      thyroid carcinoma.
AB  - Purpose: Various methods of sentinel lymph node (SLN) biopsy in thyroid cancer
      have been introduced. Tc-99m phytate as a radiotracer has been successfully
      utilized for SLN biopsy in breast, cervix, and endometrial cancer. We assessed
      the feasibility of SLN dissection using Tc-99m phytate in papillary thyroid
      carcinoma (PTC). Methods: Seventeen patients with PTC were prospectively
      enrolled. Ultrasound-guided peritumoral injection of 55.5 MBq Tc-99m phytate in
      0.25-mL normal saline was performed. Preoperative single-photon emission-computed
      tomography (SPECT) and intraoperative gamma-probe were used for SLN detection
      during operation. Results: Identification rate of SLNs was 70.6% (12 of 17) with
      SPECT, and 88.2% (15 of 17) with gamma-probe. Combined SPECT and gamma-probe had
      identification rates of 88.2% (15 of 17). Identification rates of SLNs in central
      LN compartments were 82.4% (14 of 17) and 41.2% (7 of 17) in lateral LN
      compartments. Overall sensitivity, specificity, positive predictive value, and
      negative predictive value of the results of SLN biopsy were 91.6%, 100%, 88.4%,
      and 100%, respectively. Eight patients (47.1%) had metastasis in SLNs; all
      patients had SLN metastasis in the central compartment and 2 patients had SLN
      metastasis in both the central and lateral compartments. Conclusion: Combined
      SPECT and gamma-probe could detect SLNs with an 88.2% identification rate in PTC.
      SLN biopsy using Tc-99m phytate is technically feasible. Further investigation is
      warranted for clinical application of Tc-99m phytate in PTC.

PMID- 29184877
TI  - Effect of end-to-side inverted mattress pancreaticojejunostomy following central
      pancreatectomy on the prevention of pancreatic fistula.
AB  - Purpose: Central pancreatectomy (CP) may be indicated for the treatment of benign
      or low-grade malignant tumor in the neck and proximal body of the pancreas.
      Pancreatic fistula is one of the most common complications after CP. In this
      study, we suggested an inverted mattress pancreaticojejunostomy (IM-PJ) technique
      to decrease the risk of pancreatic fistula. Methods: Between 2010 and 2015, CP
      was performed with IM-PJ for 10 consecutive patients with a benign or low-grade
      malignant tumor in the neck and proximal body of the pancreas. All clinical and
      pathological data were analyzed retrospectively. Results: Median age was 56.4
      years (range, 17-75 years). Median surgery duration was 286 minutes (range, 205
      410 minutes). In all cases, the distal stump was reconstructed using the IM-PJ
      method. Median duration of hospital stay was 23.8 days (range, 9-53 days). No
      patient mortality occurred. Pancreatic fistula developed in 9 cases (90%);
      however, all fistulas were grade A and resolved without surgical or radiological
      intervention. Nine patients remain well with no recurrence or new endocrine or
      exocrine dysfunction. Conclusion: Our results demonstrate that the outcomes of CP
      with IM-PJ are reasonable for prevention of pancreatic fistula following CP.

PMID- 29184878
TI  - Prognostic factors after curative resection hepatocellular carcinoma and the
      surgeon's role.
AB  - Purpose: Patient, surgical, and tumor factors affect the outcome after surgical
      resection for hepatocellular carcinoma (HCC). The surgical factors are only
      modifiable by the surgeon. We reviewed our experience with curative resection for
      HCC in terms of surgical factors. Methods: After analyses of the prospectively
      collected clinical data of 256 consecutive patients undergoing surgical resection
      for HCC, prognostic factors for disease-free survival (DFS) and overall survival
      (OS) were identified; all patients were stratified by tumor diameters > or <5 cm
      and their outcomes were compared. Results: Multivariate analyses showed that
      microvascular invasion, estimated blood loss, blood transfusion, and the number
      of tumors were independent adverse prognostic factors for DFS, whereas
      microvascular invasion, serum alpha fetoprotein, and tumor diameter were
      independent adverse prognostic factors for OS. Blood transfusion had borderline
      significance (P = 0.076). After stratification by tumor diameter, blood
      transfusion was only associated with poor DFS and OS in patients with tumor
      diameters > 5 cm. Conclusion: Tumor recurrence after liver resection for HCC
      depends on tumor status, bleeding, and transfusions, which subsequently lead to
      poor patient survival. Surgeons can help improve the prognosis of patients by
      minimizing blood loss and transfusion, particularly in patients with larger
      tumors.

PMID- 29184879
TI  - Three-year result of efficacy for type 2 diabetes mellitus control between
      laparoscopic duodenojejunal bypass compared with laparoscopic Roux-en-Y gastric
      bypass.
AB  - Purpose: The mechanism by which bariatric surgery facilitates diabetic control is
      still unknown. Duodenojejunal bypass supports the foregut theory; however, its
      efficacy when used alone is not yet established. Methods: During the period from
      January 2008 to December 2009, patients who underwent laparoscopic duodenojejunal
      bypass (LDJB) or laparoscopic Roux-en-Y gastric bypass (LRYGB) for type 2
      diabetes mellitus (T2DM) with or without morbid obesity were included. Patients
      who had a follow-up for less than 3 years were excluded. Patient baseline
      characteristics, change of body weight, body mass index (BMI), glycosylated
      hemoglobin (HbA1c), and diabetic treatments were analyzed. Results: In total, 8
      LDJB and 20 LRYGB patients were analyzed. The LDJB group had more number of male
      patients than the LRYGB group (LDJB 75% vs. LRYGB 30%, P = 0.030). Baseline BMI
      in the LRYGB group was higher than in the LDJB group (LDJB 27.0 +/- 2.5 vs. LRYGB
      32.6 +/- 3.4, P < 0.001). Age, DM duration, baseline HbA1c, and C-peptide levels
      were similar. Longer operation time was needed to perform LDJB (LDJB 367.5 +/-
      120.2 vs. LRYGB 232.9 +/- 41.1, P < 0.001), but no differences were observed in
      the hospital stay and complication rate between the 2 groups. At the third year
      of follow-up, the T2DM remission rate was observed in 40% of patients in the
      LRYGB group and 12.5% of patients in the LDJB group. Conclusion: LDJB is not an
      effective method for controlling T2DM compared with LRYGB. Foregut theory may not
      be the main mechanism of diabetic control during bariatric surgery.

PMID- 29184880
TI  - Histopathologic risk factors for lymph node metastasis in patients with T1
      colorectal cancer.
AB  - Purpose: Evaluating the risk of lymph node metastasis (LNM) is critical for
      determining subsequent treatments following endoscopic resection of T1 colorectal
      cancer (CRC). This study analyzed histopathologic risk factors for LNM in
      patients with T1 CRC. Methods: This study involved 745 patients with T1 CRC who
      underwent endoscopic (n = 97) or surgical (n = 648) resection between January
      2001 and December 2015 at the National Cancer Center, Korea. LNM in
      endoscopically resected patients, which could not be evaluated directly, was
      estimated indirectly based on follow-up results and histopathologic reports of
      salvage surgery. The relationships of depth of submucosal invasion, histologic
      grade, budding, vascular invasion, and background adenoma with LNM were evaluated
      statistically. Results: Of the 745 patients, 91 (12.2%) were found to be positive
      for LNM. Univariate and multivariate analyses identified deep submucosal invasion
      (P = 0.010), histologic high grade (P < 0.001), budding (P = 0.034), and vascular
      invasion (P < 0.001) as risk factors for LNM. Among the patients with one, two,
      three, and four risk factors, 6.0%, 18.7%, 36.4%, and 100%, respectively, were
      positive for LNM. Conclusion: Deep submucosal invasion, histologic high grade,
      budding, and vascular invasion are risk factors for LNM in patients with T1
      colorectal cancer. If any of these risk factors are present, additional surgery
      following endoscopic resection should be determined after considering the
      potential risk of LNM and each patient's situation.

PMID- 29184882
TI  - Cutaneous metastasis: a rare phenomenon of colorectal cancer.
AB  - Cutaneous metastases from colorectal cancer are extremely rare and generally
      appear several years after diagnosis or resection of the primary tumor. Although
      this phenomenon is uncommon, it is very important and often indicates a poor
      prognosis. We present a case of a 76-year-old female patient with multiple
      cutaneous metastatic nodules on the back, just 1 month after resection of rectal
      cancer. Unfortunately, the patient gave up the follow-up treatment due to her age
      and poor physical condition; she died 3 months later. In view of its rarity of
      occurrence and lack of experience in treatment, we reviewed the literature and
      report as follows.

PMID- 29184881
TI  - Which patients with intestinal obstruction need surgery? The delta neutrophil
      index as an early predictive marker.
AB  - Purpose: Predicting the need for surgical intervention among patients with
      intestinal obstruction is challenging. The delta neutrophil index (DNI) has been
      suggested as a useful marker of immature granulocytes, which indicate an
      infection or sepsis. In this study, we evaluated the impact of the DNI as an
      early predictor of operation among patients with intestinal obstruction. Methods:
      A total of 171 patients who were diagnosed with postoperative intestinal
      obstruction were enrolled in this study. Medical records, including data for the
      initial CRP level, WBC count, and DNI were reviewed. Receiver operating
      characteristic (ROC) curves were generated to clarify the optimal DNI cutoff
      values for predicting an operation. Results: Among the 171 patients, 38 (22.2%)
      needed surgical intervention. The areas under the initial CRP, WBC, and DNI ROC
      curves were 0.460, 0.449, and 0.543, respectively. The optimal cutoff value for
      predicting further surgical intervention according to the initial DNI level was
      4.3%. The accuracy of the cutoff value was 74.9%, the sensitivity was 23.7%, and
      the specificity was 89.5% (positive predictive value, 23.7%; negative predictive
      value, 89.5%). In the multivariate analysis, initial DNI levels >= 4.3% were
      significantly associated with surgical intervention (odd ratio, 3.092; 95%
      confidence interval, 1.072-8.918; P = 0.037). Conclusion: The initial DNI level
      in patients with intestinal obstruction may be a useful predictor for determining
      the need for surgical intervention.

PMID- 29184883
TI  - Small bowel obstruction caused by cryptorchidism in an adult.
AB  - Small bowel obstruction (SBO) is a common complication after abdominal surgery,
      and can occur due to many reasons. However, cryptorchidism can cause SBO in
      patients with no history of abdominal surgery. We report the case of a 67-year
      old man with SBO caused by adhesions between an undescended testis and the
      terminal ileum.

PMID- 29184884
TI  - Single port laparoscopic repair of sigmoid colon perforation during colonoscopy.
AB  - Colonic perforation during colonoscopy is a rare but lethal complication.
      Recently, it is usually managed with laparoscopic approach. Here we present our
      experience of single incision laparoscopic repair for sigmoid colon perforation
      during colonoscopy. A 57-year-old male patient presented with an acute sigmoid
      colon perforation event during diagnostic colonoscopy. Emergency operation was
      performed with transumbilical single incision laparoscopic exploration. The
      perforated site of sigmoid colon was primarily repaired with the curved
      endoscopic linear stapler. The patient was discharged after 5 days uneventfully.
      Single port laparoscopic repair is a safe and feasible method for the management
      of acute colonoscopic perforation during diagnostic colonoscopy.

PMID- 29184885
TI  - Sudden Infant Death Syndrome, Infection, Prone Sleep Position, and Vagal
      Neuroimmunology.
AB  - Recent findings suggest that infection (and sepsis) stand alone as the only
      plausible mechanism of causation of sudden infant death syndrome (SIDS) and
      accordingly achieves congruence with all clinicopathological and epidemiological
      findings. This review examines the role of infection in the pathogenesis of SIDS
      in the context of the major risk factor of prone sleep position. The study
      explores how sleep position could interact with the immune system and
      inflammatory response via vagal neural connections, which could play key roles in
      gut and immune homeostasis. A plausible and congruent clinicopathological and
      epidemiological paradigm is suggested.

PMID- 29184886
TI  - Expression Profiling of Ribosomal Protein Gene Family in Dehydration Stress
      Responses and Characterization of Transgenic Rice Plants Overexpressing RPL23A
      for Water-Use Efficiency and Tolerance to Drought and Salt Stresses.
AB  - Our previous findings on the screening of a large-pool of activation tagged rice
      plants grown under limited water conditions revealed the activation of Ribosomal
      Protein Large (RPL) subunit genes, RPL6 and RPL23A in two mutants that exhibited
      high water-use efficiency (WUE) with the genes getting activated by the
      integrated 4x enhancers (Moin et al., 2016a). In continuation of these findings,
      we have comprehensively characterized the Ribosomal Protein (RP) gene family
      including both small (RPS) and large (RPL) subunits, which have been identified
      to be encoded by at least 70 representative genes; RP-genes exist as multiple
      expressed copies with high nucleotide and amino acid sequence similarity. The
      differential expression of all the representative genes in rice was performed
      under limited water and drought conditions at progressive time intervals in the
      present study. More than 50% of the RP genes were upregulated in both shoot and
      root tissues. Some of them exhibited an overlap in upregulation under both the
      treatments indicating that they might have a common role in inducing tolerance
      under limited water and drought conditions. Among the genes that became
      significantly upregulated in both the tissues and under both the treatments are
      RPL6, 7, 23A, 24, and 31 and RPS4, 10 and 18a. To further validate the role of RP
      genes in WUE and inducing tolerance to other stresses, we have raised transgenic
      plants overexpressing RPL23A in rice. The high expression lines of RPL23A
      exhibited low Delta13C, increased quantum efficiency along with suitable growth
      and yield parameters with respect to negative control under the conditions of
      limited water availability. The constitutive expression of RPL23A was also
      associated with transcriptional upregulation of many other RPL and RPS genes. The
      seedlings of RPL23A high expression lines also showed a significant increase in
      fresh weight, root length, proline and chlorophyll contents under simulated
      drought and salt stresses. Taken together, our findings provide a secure basis
      for the RPL gene family expression as a potential resource for exploring abiotic
      stress tolerant properties in rice.

PMID- 29184887
TI  - Weak Molecular Interactions in Clathrin-Mediated Endocytosis.
AB  - Clathrin-mediated endocytosis is a process by which specific molecules are
      internalized from the cell periphery for delivery to early endosomes. The key
      stages in this step-wise process, from the starting point of cargo recognition,
      to the later stage of assembly of the clathrin coat, are dependent on weak
      interactions between a large network of proteins. This review discusses the
      structural and functional data that have improved our knowledge and understanding
      of the main weak molecular interactions implicated in clathrin-mediated
      endocytosis, with a particular focus on the two key proteins: AP2 and clathrin.

PMID- 29184889
TI  - The conceptualization of a Just-In-Time Adaptive Intervention (JITAI) for the
      reduction of sedentary behavior in older adults.
AB  - Low physical activity and high sedentary behavior in older adults can be
      addressed with interventions that are delivered through modern technology. Just
      In-Time Adaptive Interventions (JITAIs) are an emerging technology-driven
      behavior-change intervention type and capitalize on data that is collected via
      mobile sensing technology (e.g., smartphones) to trigger appropriate support in
      real-life. In this paper we integrated behavior change and aging theory and
      research as well as knowledge around older adult's technology use to
      conceptualize a JITAI targeting the reduction of sedentary behavior in older
      adults. The JITAIs ultimate goal is to encourage older adults to take regular
      activity breaks from prolonged sitting. As a proximal outcome, we suggest the
      number of daily activity breaks from sitting. Support provided to interrupt
      sitting time can be based on tailoring variables: (I) the current accumulated
      sitting time; (II) the location of the individual; (III) the time of the day;
      (IV) the frequency of daily support prompts; and (V) the response to previous
      support prompts. Data on these variables can be collected using sensors that are
      commonly inbuilt into smartphones (e.g., accelerometer, GPS). Support prompts
      might be best delivered via traditional text messages as older adults are usually
      familiar and comfortable with this function. The content of the prompts should
      encourage breaks from prolonged sitting by highlighting immediate benefits of
      sitting time interruptions. Additionally, light physical activities that could be
      done during the breaks should also be presented (e.g., walking into the kitchen
      to prepare a cup of tea). Although the conceptualized JITAI can be developed and
      implemented to test its efficacy, more work is required to identify ways to
      collect, aggregate, organize and immediately use dense data on the proposed and
      other potentially important tailoring variables. Machine learning and other
      computational modelling techniques commonly used by computer scientists and
      engineers appear promising. With this, to develop powerful JITAIs and to
      actualize the full potential of modern sensing technologies transdisciplinary
      approaches are required.

PMID- 29184890
TI  - Digital health is a cultural transformation of traditional healthcare.
AB  - Under the term "digital health", advanced medical technologies, disruptive
      innovations and digital communication have gradually become inseparable from
      providing best practice healthcare. While the cost of treating chronic conditions
      is increasing and doctor shortages are imminent worldwide, the needed
      transformation in the structure of healthcare and medicine fails to catch up with
      the rapid progress of the medical technology industry. This transition is slowed
      down by strict regulations; the reluctance of stakeholders in healthcare to
      change; and ignoring the importance of cultural changes and the human factor in
      an increasingly technological world. With access and adoption of technology
      getting higher, the risk of patients primarily turning to an accessible, but
      unregulated technological solution for their health problem is likely to
      increase. In this paper, we discuss how the old paradigm of the paternalistic
      model of medicine is transforming into an equal level partnership between
      patients and professionals and how it is aided and augmented by disruptive
      technologies. We attempt to define what digital health means and how it affects
      the status quo of care and also the study design in implementing technological
      innovations into the practice of medicine.

PMID- 29184891
TI  - The role of mHealth intervention on maternal and child health service delivery:
      findings from a randomized controlled field trial in rural Ethiopia.
AB  - Background: The provision of consistent and quality maternal and child health
      (MCH) services is a challenge for Ethiopia where most of the population lives in
      the rural setup. Health service delivery is constrained mainly by shortage of
      health professionals, meager resources, limited awareness among the society and
      bureaucratic procedures. Low health service utilization of antenatal care (ANC),
      delivery services, and postnatal care (PNC) are believed to contribute for high
      maternal and child mortality rates. Innovative approach like mHealth based
      technological intervention believed to alleviate such challenges in countries
      like ours. However, currently, there are few evidences that demonstrate the
      impact of mHealth technology applications on the level of service utilization.
      Therefore, the objective our study is to assess the role of mobile phone equipped
      with short message service (SMS) based data-exchange software linking community
      health workers to Health Centers in rural Ethiopia affect selected MCH outcomes.
      Methods: A community-based randomized control trial (RCT) was conducted in three
      woredas of Guraghe zone (Ezha, partial &Abeshge full intervention, Sodo Control).
      Mobile phones equipped with FrontlineSMS based, locally developed application was
      distributed to all health extension workers (HEWs) to both intervention woredas
      who filled maternal, child and stock related forms and submitted to the central
      server which in turn sends reminder about the scheduled date of ANC visit,
      expected date of delivery, PNC, immunization schedule and vaccine and
      contraceptive stock status. Moreover, in Abeshge, the voluntary health workers
      (vCHW) and HEW supervisors in both intervention woreda were given a phone to
      facilitate communication with the HEW. No mobile was offered to the control
      woreda.Pre [2012] and post [2013] intervention community based survey on mothers
      who have under 5 and under 1 year old child was done to assess the effect of the
      mobile intervention on selected MCH process indicators. Structured and pretested
      questionnaire was used to collect data and SPSS v16 statistical software was used
      for analysis. Results: Three thousand two hundred and forty mothers, 1,080 from
      each, were surveyed in the three woredas. The study revealed that the proportion
      of mothers receiving more than four ANC visits increased significantly in both
      intervention woredas. Besides, the rate of ANC delivered by HEWs improved in Ezha
      woreda (T1) (19.01% to 28.27%), proportions of deliveries attended by skilled
      health workers increased and home delivery decreased in all woredas; most
      pronounced increases in referrals from health post to health center by HEWs,
      reported in Ezha and Abeshge. The intervention also led to a significant
      reduction in stock-outs of preferred contraceptive products in Ezha (T1) from
      16.96% to 8.24% but no change was observed in both contraceptive prevalence and
      immunization rates in the control and the other intervention woreda. Conclusions:
      The study confirmed the positive contribution of SMS based mobile phone
      intervention in most of the selected MCH service indicators, like improvement in
      the percent of recommended number of ANC visit, percentage of delivery attended
      by health workers and facilitating the work processes of the health workers in
      rural Ethiopia.

PMID- 29184892
TI  - BLOODR: blood donor and requester mobile application.
AB  - Background: With rapid increase in the usage of social networks sites across the
      world, there is also a steady increase in blood donation requests as being
      noticed in the number of posts on these sites such as Facebook and twitter
      seeking blood donors. Finding blood donor is a challenging issue in almost every
      country. There are some blood donor finder applications in the market such as
      Blood app by Red Cross and Blood Donor Finder application by Neologix. However,
      more reliable applications that meet the needs of users are prompted. Methods:
      Several software technologies including languages and framework are used to
      develop our blood-donor web application known as BLOODR application. These
      technologies comprise Ruby programming language (simply known as Ruby) along with
      JavaScript and PostgreSQL for database are used. Ruby on Rails (simply known as
      Rails) is an open source Web framework that makes it possible to quickly and
      easily create data-based web applications. Results: We show screenshots for the
      BLOODR application for different types of users including requester, donor, and
      administrator. Various features of the application are described and their needs
      of use are analyzed. If a patient needs a blood at a clinic, blood donors in
      vicinity can be contacted through using a clinic management service provided in
      this application. Registered donors will get notification for the blood requests
      only if their blood group is compatible with the requested blood type and in the
      same city/region. Then matching blood donors can go to the requesting clinic and
      donate. Conclusions: BLOODR application provides a reliable platform to connect
      local blood donors with patients. BLOODR creates a communication channel through
      authenticated clinics whenever a patient needs blood donation. It is a useful
      tool to find compatible blood donors who can receive blood request posts in their
      local area. Clinics can use this web application to maintain the blood donation
      activity. Future improvement of the BLOODR is explained.

PMID- 29184888
TI  - Targeting DNA Replication and Repair for the Development of Novel Therapeutics
      against Tuberculosis.
AB  - Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), an
      infectious disease which results in approximately 10 million incident cases and
      1.4 million deaths globally each year, making it the leading cause of mortality
      from infection. An effective frontline combination chemotherapy exists for TB;
      however, this regimen requires the administration of four drugs in a 2 month long
      intensive phase followed by a continuation phase of a further 4 months with two
      of the original drugs, and is only effective for the treatment of drug-sensitive
      TB. The emergence and global spread of multidrug-resistant (MDR) as well as
      extensively drug-resistant (XDR) strains of M. tuberculosis, and the
      complications posed by co-infection with the human immunodeficiency virus (HIV)
      and other co-morbidities such as diabetes, have prompted urgent efforts to
      develop shorter regimens comprising new compounds with novel mechanisms of
      action. This demands that researchers re-visit cellular pathways and functions
      that are essential to M. tuberculosis survival and replication in the host but
      which are inadequately represented amongst the targets of current anti
      mycobacterial agents. Here, we consider the DNA replication and repair machinery
      as a source of new targets for anti-TB drug development. Like most bacteria, M.
      tuberculosis encodes a complex array of proteins which ensure faithful and
      accurate replication and repair of the chromosomal DNA. Many of these are
      essential; so, too, are enzymes in the ancillary pathways of nucleotide
      biosynthesis, salvage, and re-cycling, suggesting the potential to inhibit
      replication and repair functions at multiple stages. To this end, we provide an
      update on the state of chemotherapeutic inhibition of DNA synthesis and related
      pathways in M. tuberculosis. Given the established links between genotoxicity and
      mutagenesis, we also consider the potential implications of targeting DNA
      metabolic pathways implicated in the development of drug resistance in M.
      tuberculosis, an organism which is unusual in relying exclusively on de novo
      mutations and chromosomal rearrangements for evolution, including the acquisition
      of drug resistance. In that context, we conclude by discussing the feasibility of
      targeting mutagenic pathways in an ancillary, "anti-evolution" strategy aimed at
      protecting existing and future TB drugs.

PMID- 29184893
TI  - Global mHealth policy arena: status check and future directions.
AB  - In this review, we examine an important piece of the mHealth puzzle that has
      received scant attention-health policy. The question is whether health policy
      ultimately will serve to unite nations in advancing global mHealth or, as Mars
      and Scott suggested in 2010, keep nations isolated and ultimately making their
      policy decisions in "eHealth silos". Such a non-collaborative approach seriously
      hampers the potential for using mobile health technologies to deliver health care
      across borders, assuring individuals access to affordable, convenient, and
      quality healthcare in underserved regions. From a global perspective, mHealth
      policy review is difficult as some important policies may be subsumed in
      comprehensive planning and strategy documents. Political, environmental,
      economic, organizational, and technology disparities across nations represent a
      significant impediment to developing mHealth products and services that can be
      deployed globally. To date, there is modest evidence that such challenges are
      being addressed. Even though payers can encourage adoption of mHealth with
      financial incentives for use, it appears that payment or reimbursement tends to
      be a roadblock for almost all nations, whether they are emerging or developed. If
      payment for mHealth services is not guaranteed, business models will not be
      sustainable and providers will have fewer opportunities for scalability.
      Furthermore, because mHealth policies typically are subject to some type of
      government scrutiny and oversight, many product developers and entrepreneurs may
      turn elsewhere for their investments. Global resource scarcity also challenges
      optimal mHealth deployment, and governments seek to ensure improved population
      health outcomes as return on their mHealth investments. Unfortunately, such
      justification is difficult as evaluation methods simply have not kept pace with
      mHealth technology capability. Requisite measurement tools are sorely lacking
      when it comes to evaluating efficacy of mHealth interventions, due in part to
      insufficient research to inform development of needed measurement tools. Because
      most robust mHealth research trials have been conducted in the developed world
      with its impressive technology infrastructure and not in developing nations where
      the health needs are greatest, evaluation of mobile technology intervention from
      a global perspective tends to be insufficient to inform policy decisions.

PMID- 29184894
TI  - Effect of mHealth on modifying behavioural risk-factors of non-communicable
      diseases in an adult, rural population in Delhi, India.
AB  - Background: The rising trend of non-communicable diseases (NCDs) has led to a
      "dual burden" in low and middle-income (LAMI) countries like India which are
      still battling with high prevalence of communicable diseases. The incorporation
      of a target specially dedicated to NCDs within the goal 3 of the newly adopted
      Sustainable Development Goals indicates the importance the world now accords to
      prevention and control of these diseases. Mobile phone technology is increasingly
      viewed as a promising communication channel that can be utilized for primary
      prevention of NCDs by promoting behaviour change and risk factor modification.
      Methods: A "Before and After" Intervention study was conducted on 400 subjects,
      over a period of one year, in Barwala village, Delhi, India. An mHealth
      intervention package consisting of weekly text messages and monthly telephone
      calls addressing lifestyle modification for risk factors of NCDs was given to the
      intervention group, compared to no intervention package in control group.
      Results: After Intervention Phase, significant reduction was seen in behavioural
      risk factors (unhealthy diet and insufficient physical activity) in the
      intervention group compared to control group. Body mass index (BMI), systolic
      blood pressure and fasting blood sugar level also showed significant difference
      in the intervention group as compared to controls. Conclusions: Our study has
      demonstrated the usefulness of mHealth for health promotion and lifestyle
      modification at community level in a LAMI country. With the growing burden of
      NCDs in the community, such cost effective and innovative measures will be needed
      that can easily reach the masses.

PMID- 29184895
TI  - Impact of an iDevice application on student learning in an occupational therapy
      kinesiology course.
AB  - Background: As technology continues to evolve, and information is increasingly
      accessed through smartphones and tablets, it is essential for university faculty
      to reassess teaching methodologies. This study explored how use of an iDevice
      application (app) by participants enrolled in an entry-level occupational therapy
      kinesiology course affected student learning in the course. This iDevice app was
      developed through a collaboration between the lead author and the Department of
      Technology Enhanced Learning and Innovation at Augusta University. Methods: The
      iDevice app was released to the public via the Apple(r) App Store at the midpoint
      of the kinesiology course. All students were invited to use the app. Focus groups
      were conducted with 19 students recruited from the first year cohort of
      occupational therapy graduate students. These focus groups were conducted at the
      end of the semester once grades had been submitted. Results: Thematic analysis of
      focus group transcripts revealed three themes reflecting how participants
      perceived app use impacting their learning. Participants report the app
      facilitated learning through provision of visual content, serving as a reliable
      source of information, and generally supporting the learning process. The
      Kinesiology Pro Consult App provided on demand learning, allowing students to be
      more autonomous with their learning and take advantage of opportunities to learn
      anywhere and anytime. Finally, participants reported the app allowed them to be
      more efficient in their learning, possibly allowing more time for other courses.
      Conclusions: Mobile device apps that support student learning in specific content
      areas may provide positive benefits to student learning both in the specific
      course related to the app but also in other courses as a result of increased
      efficiency in learning.

PMID- 29184896
TI  - Formative evaluation on cultural tailoring breathing awareness meditation
      smartphone apps to reduce stress and blood pressure.
AB  - Background: Chronic stress is an independent risk factor for essential
      hypertension (EH), cardiovascular disease (CVD), and is sometimes confronted by
      mal-adaptive coping behaviors (e.g., stress eating, excessive alcohol
      consumption, etc.). Pre-essential hypertension (preEH) is the leading predictor
      of future EH status. Breathing awareness meditation (BAM) can result in
      clinically beneficial blood pressure (BP) reductions, though face-to-face
      sessions presents barriers to reach those in need. The purpose of this study was
      to identify if a culturally tailored approach is needed in the design and
      preferences between groups of preEH African American and White adults toward
      using a smartphone BAM app, the Tension Tamer (TT) app. Methods: TT includes
      audio delivered BAM instructions, real-time heart rate, feedback graphs and
      motivational reinforcement text messaging. Questionnaires and two focus groups
      each of African American and White adults, [n=34, mean age =43.1 years, (SD 13.8
      years), 44.1% African American] were conducted to understand stress, EH
      knowledge, app usage along with feedback from a hands-on demonstration of TT.
      Grounded theory using NVivo 10 was used to develop themes and combined with the
      questionnaires in the analysis. Results: No racial differences were found in the
      analysis including app use scenarios, preferences, knowledge, technology use or
      the attitudes and acceptance toward mobile health (mHealth) programs. Reported
      stress was high for African Americans [PSS-4: mean 6.87 (SD 3.3) versus mean 4.56
      (SD 2.6); P=0.03]. Four main themes were found: (I) stress was pervasive; (II)
      coping strategies were both positive and negative; (III) BAM training was easy to
      incorporated; and (IV) tracking stress responses was useful. Responses suggest
      that additional personalization of app interfaces may drive ownership and
      adherence to protocols. Measures and reports of heart rate monitoring while in
      session were favorably viewed with low issues with confidentiality or trust
      issues on collected session data. Conclusions: Results suggest that a culturally
      tailored approach may be unnecessary in the design of BAM apps. Further
      investigation is warranted for other racial groups, age ranges, and disease
      conditions.

PMID- 29184897
TI  - Deep learning for cardiac computer-aided diagnosis: benefits, issues & solutions.
AB  - Cardiovascular diseases are one of the top causes of deaths worldwide. In
      developing nations and rural areas, difficulties with diagnosis and treatment are
      made worse due to the deficiency of healthcare facilities. A viable solution to
      this issue is telemedicine, which involves delivering health care and sharing
      medical knowledge at a distance. Additionally, mHealth, the utilization of mobile
      devices for medical care, has also proven to be a feasible choice. The
      integration of telemedicine, mHealth and computer-aided diagnosis systems with
      the fields of machine and deep learning has enabled the creation of effective
      services that are adaptable to a multitude of scenarios. The objective of this
      review is to provide an overview of heart disease diagnosis and management,
      especially within the context of rural healthcare, as well as discuss the
      benefits, issues and solutions of implementing deep learning algorithms to
      improve the efficacy of relevant medical applications.

PMID- 29184898
TI  - Potential benefits of using ecological momentary assessment to study high-risk
      polydrug use.
AB  - Background: While studies have documented both the feasibility and acceptability
      of using ecological momentary assessment (EMA) to study drug use, there is little
      empirical research assessing participants' perceptions of utilizing this
      technology-driven approach. Methods: Participants were English-speaking persons
      >=18 years old who reported injection drug use and sequential (e.g., alcohol
      followed by opioid use) or simultaneous (i.e., injecting heroin and cocaine in
      one shot) polydrug use within 30 days recruited in San Diego, CA and
      Philadelphia, PA. Participants (N=36) completed two cell phone-based EMA
      simulations assessing mood, drug use, HIV risk behaviors, and daily activities,
      followed by semi-structured interviews that probed for potential benefits of
      participation over time. Qualitative analysis involved an iterative process of
      reviewing texts from the interviews to create a coding framework, which was then
      applied to all transcripts to identify themes. Results: Findings suggest
      participants may derive indirect benefits from participation in EMA studies
      including: improved self-worth from helping others; experiencing increased social
      support through utilization of the study-provided mobile device for non-research
      purposes; and most importantly, increased self-reflection, which could lead to
      therapeutic and intervention-like effects such as decreased substance use or
      reduced HIV risk. Conclusions: Participants identified a variety of potential
      benefits from participating in a study that utilizes EMA. This research suggests
      that benefits are highly salient for individuals involved in studies of polydrug
      use.

PMID- 29184900
TI  - Onto the bull's eye.
AB  - People set goals to improve their overall health and well-being. Unfortunately,
      people often lose motivation to achieve their goals because they fail to set
      proper goals. Goalify is a free mobile app with paid features that can help
      people set, achieve and maintain goals. It follows Locke and Latham strategies
      for successful goal setting. To gain greater control over their lives, we
      recommend readers to use a theory-based mobile app to set, log and achieve their
      goals.

PMID- 29184899
TI  - Mobile technology for self-monitoring of blood glucose among patients with type 2
      diabetes mellitus.

PMID- 29184901
TI  - Evaluating and improving recruitment and retention in an mHealth clinical trial:
      an example of iterating methods during a trial.
AB  - Background: Recruitment and retention strategy investigations in mHealth clinical
      trials are rare. Technology presents an opportunity to intensely and remotely
      evaluate recruitment, use of mobile apps, and retention, leading to new insights
      for continuous improvement of mHealth trials. The objective of this paper is to
      present a case study in which a trial evaluated and changed strategies during a
      clinical trial to improve recruitment, adherence to study protocols, and
      retention in the mHealth trial. Methods: In Fall 2015, the NUYou trial enrolled
      150 college freshmen in an mHealth protocol. Three months after study initiation,
      NUYou struggled to meet recruitment goals and maintain anticipated usage levels
      of the study smartphone application. Two sets of data were collected to improve
      recruitment and retention: a survey about recruitment was sent to the target
      population and surveys regarding usability of the app was sent to the study
      sample. Survey results informed improvements in recruitment strategies, the study
      retention protocol, and the smartphone application. Results: Survey results
      revealed several insights including misunderstanding components of the trial by
      potential participants, low perceived usefulness of the app, and little recall or
      impact of the incentive structure. After implementation of user-centered
      improvements, the second cohort of NUYou recruitment in the fall of 2016 produced
      an equal sample size in 4 weeks less time. Winter quarter of 2016 compared to
      2017 demonstrated an improvement in retention via app use and completion of
      weekly in-app surveys. Conclusions: Recruitment and retention in clinical trials
      continues to be a critical challenge and mHealth trials may present both unique
      challenges and opportunities. To our knowledge, this is the first study to
      describe a systematic evaluation followed by changes and further evaluation to
      recruitment, use of the mHealth application, adherence to study protocol, and
      retention during an mHealth clinical trial. Future work should adopt and
      explicitly study these processes to optimize both enrollment and retention in
      these types of trials to preserve validity and reliability of research results.

PMID- 29184903
TI  - International roadmap for artificial gravity research.
AB  - In this paper, we summarize the current and future research activities that will
      determine the requirements for implementing artificial gravity (AG) to mitigate
      the effects of long duration exposure to microgravity on board exploration class
      space vehicles. NASA and its international partners have developed an AG roadmap
      that contains a common set of goals, objectives, and milestones. This roadmap
      includes both ground-based and space-based projects, and involves human subjects
      as well as animal and cell models. It provides a framework that facilitates
      opportunities for collaboration using the full range of AG facilities that are
      available worldwide, and a forum for space physiologists, crew surgeons,
      astronauts, vehicle designers, and mission planners to review, evaluate, and
      discuss the issues of incorporating AG technologies into the vehicle design.

PMID- 29184904
TI  - Erratum: Resting and Exercise Energy Metabolism After Liver Transplantation for
      Nonalcoholic Steatohepatitis: Erratum.
AB  - [This corrects the article DOI: 10.1097/TXD.0000000000000701.].

PMID- 29184905
TI  - Frequency of In-Home Internet Use Among Prekidney and Postkidney Transplant
      Patients-Facilitators and Barriers to Use and Trends Over Time.
AB  - Background: As health-related communications become digitized, strategies to
      increase adoption of these Web-based platforms are needed. The purpose of this
      study was to assess facilitators and barriers to in-home Internet use among
      prekidney and postkidney transplant patients. Methods: A single center, cross
      sectional survey of 240 consecutive patients of all levels of technological
      proficiency who presented to an urban transplant center in the United States. The
      Patient Information and Technology Assessment consists of 6 demographic
      questions, 3 disease-related questions, and 8 technology-related questions.
      Results: Much of the sample was African American, male with a mean age of 51
      years, and median income of $53 800/year. Logistic regression analysis was
      undertaken, and after adjusting for covariates, we found Smartphone ownership
      (odds ratio [OR], 4.94; 95% confidence interval [CI], 2.32-10.52), a higher
      number of Internet users in the home (OR, 2.00; 95% CI, 1.11-3.62), and having
      college education and beyond (OR, 4.88; 95% CI, 2.03-11.74) increased the
      likelihood of being a frequent Internet user. African American or Hispanic/Latino
      patients were less likely to be frequent Internet users compared with white
      patients (OR, 0.26 and 0.24, respectively, compared with whites, all P < 0.05).
      As the total number of people in the household increased, frequent Internet use
      decreased (OR, 0.52; 95% CI, 0.29-0.92). As age increased, reports of frequent
      Internet use decreased. Conclusions: Lower rates of Internet use among African
      Americans and Hispanic/Latinos in urban areas in the United States remains a
      problem despite a significant increase in access to the Internet and Smartphone
      ownership. The finding that Internet use increases as the number of Internet
      users in the household increases indicates that leveraging the patient's social
      support network and/or the development of patient information champion programs
      may aid with patient's adoption of health technology and patient engagement in
      self-care.

PMID- 29184902
TI  - Vertebrate food products as a potential source of prion-like alpha-synuclein.
AB  - The aberrant aggregation of the protein alpha-synuclein is thought to be involved
      in Parkinson's disease (PD). However, the factors that lead to initiation and
      propagation of alpha-synuclein aggregation are not clearly understood. Recently,
      the hypothesis that alpha-synuclein aggregation spreads via a prion-like
      mechanism originating in the gut has gained much scientific attention. If alpha
      synuclein spreads via a prion-like mechanism, then an important question becomes,
      what are the origins of this prion-like species? Here we review the possibility
      that alpha-synuclein aggregation could be seeded via the ingestion of a prion
      like alpha-synuclein species contained within food products originating from
      vertebrates. To do this, we highlight current evidence for the gut-to-brain
      hypothesis of PD, and put this in context of available routes of alpha-synuclein
      prion infectivity via the gastrointestinal (GI) tract. We then discuss meat as a
      ready exogenous source of alpha-synuclein and how certain risk factors, including
      inflammation, may allow for dietary alpha-synuclein to pass from the GI lumen
      into the host to induce pathology. Lastly, we review epidemiological evidence
      that dietary factors may be involved in PD. Overall, research to date has yet to
      directly test the contribution of dietary alpha-synuclein to the mechanism of
      initiation and progression of the disease. However, numerous experimental
      findings, including the potent seeding and spreading behavior of alpha-synuclein
      fibrils, seem to support, at least in part, the feasibility of an infection with
      a prion alpha-synuclein particle via the GI tract. Further studies are required
      to determine whether dietary alpha-synuclein contributes to seeding pathology in
      the gut.

PMID- 29184906
TI  - Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation:
      Evaluating Cell Donors and Recipients.
AB  - Background: Parvovirus B19 (B19V) is a common human pathogen, member of the
      family Parvoviridae. Typically, B19V has been found to infect erythroid
      progenitors and cause hematological disorders, such as anemia and aplastic
      crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been
      demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as
      well as bone marrow, for both symptomatic and asymptomatic subjects. Although the
      molecular and cellular mechanisms of persistence remain undefined, it raises
      questions about potential virus transmissibility and its effects in the context
      of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.
      Methods: With this aim, we retrospectively screened allogeneic stem cell donors
      from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a
      seminested polymerase chain reaction approach. Results: We found 8 positive donor
      samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36
      8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive
      donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT
      follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype
      of isolates and classification, performed by phylogenetic reconstruction, showed
      a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2
      additional patients. By molecular cloning, different B19V 1a substrains
      polymorphisms were evidenced in the single case in which donor and its recipient
      were B19V+. Conclusions: Our results suggest that HSCT allografts are not a main
      source for B19V transmission, pointing to potential events of reinfection or
      endogenous viral reactivation.

PMID- 29184907
TI  - Comparative Assessment of Anti-HLA Antibodies Using Two Commercially Available
      Luminex-Based Assays.
AB  - Background: Allospecific anti-HLA antibodies (Abs) are associated with rejection
      of solid organ grafts. The 2 main kits to detect anti-HLA Ab in patient serum are
      commercialized by Immucor and One Lambda/ThermoFisher. We sought to compare the
      performance of both platforms. Methods: Background-adjusted mean fluorescence
      intensity (MFI) values were used from both platforms to compare sera collected
      from 125 pretransplant and posttransplant heart and lung transplant recipients.
      Results: Most HLA class I (94.5%) and HLA class II (89%) Abs with moderate to
      high MFI titer (>=4000) were detected by both assays. A modest correlation was
      observed between MFI values obtained from the 2 assays for both class I (r = 0.3,
      r2 = 0.09, P < 0.0001) and class II Ab (r = 0.707, r2 = 0.5, P < 0.0001). Both
      assays detected anti-class I and II Ab that the other did not; however, no
      specific HLA allele was detected preferentially by either of the 2 assays. For a
      limited number of discrepant sera, dilution resulted in comparable reactivity
      profiles between the 2 platforms. Conclusions: Immucor and One
      Lambda/ThermoFisher assays have a similar, albeit nonidentical, ability to detect
      anti-HLA Ab. Although the correlation between the assays was present, significant
      variances exist, some of which can be explained by a dilution-sensitive "prozone"
      effect.

PMID- 29184908
TI  - Hypothesis: Potential Utility of Serum and Urine Uromodulin Measurement in Kidney
      Transplant Recipients?
AB  - Seventy years after its discovery, studies of the myriad properties, and
      potential disease associations of uromodulin are now burgeoning. Although
      normative ranges for serum/plasma uromodulin concentrations were established over
      30 years ago, their external validation occurred only in very recent, larger
      studies. As tubular function indices, serum and urinary uromodulin may be more
      sensitive indicators of kidney graft dysfunction undetected by glomerular
      filtration markers, or proteinuria. Moreover, 2 sizable, just published
      longitudinal reports revealed that lower serum uromodulin levels were associated
      with cardiovascular disease (CVD) outcomes, total mortality, and infectious
      disease deaths, in patients with known or suspected coronary heart disease.
      Preliminary longitudinal studies have reported that reduced levels of plasma or
      serum uromodulin were linked to progression to end-stage renal disease in chronic
      kidney disease patients, and graft failure in kidney transplant recipients
      (KTRs). Conflicting data on the associations, or lack thereof, between lower
      urinary uromodulin concentrations and accelerated loss of renal function, or
      renal failure, in nontransplant chronic kidney disease patients, are perhaps due,
      in part, to analytical limitations in determining urine uromodulin. Potential
      longitudinal associations between serum and urinary uromodulin concentrations,
      and CVD outcomes, graft failure, and all-cause mortality, await validation in
      large, diverse cohorts of chronic KTRs. Taking advantage of an efficient case
      cohort design scheme, we demonstrate how the completed FAVORIT clinical trial
      cohort might be ideally suited to evaluate these associations. Using available
      case-cohort sample data, statistical power simulations are provided to detect
      relative risk estimates of 1.50 for CVD (n = 309 events), 1.56 for graft failure
      (n = 223 events) or 1.50 for death from any cause (n = 320 events), comparing
      values below the median, to values equal to or above the median for serum
      uromodulin values. Edifying data such as these would advance our understanding of
      the hypothetical utility of uromodulin measurement in KTRs considerably.

PMID- 29184909
TI  - Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft
      Rejection in a Small Bowel Transplant Rat Model.
AB  - Background: Intestinal transplantation (ITx) faces many challenges due to the
      complexity of surgery and to the multiple immunological reactions that lead to
      the necessity of rigorous follow-up for early detection of acute cellular
      rejection (ACR). Our aim was to determine the kinetics of ACR using an
      experimental ITx model, with emphasis in the characterization of the process
      using different approaches, including the use of functional assays of absorptive
      and barrier function. Methods: ITx in rats conducting serial sampling was
      performed. Clinical monitoring, graft histology, proinflammatory gene expression,
      and nitrosative stress determination were performed. Also, glucose absorption,
      barrier function using ovalbumin translocation, and contractile function were
      analyzed. Results: The model used reproduced the different stages of ACR.
      Allogeneic ITx recipients showed signs of rejection from postoperative day (POD)
      5, with increasing severity until 12 POD. Histological evaluation showed mild
      rejection in early sampling and severe rejection at late stages, with alterations
      in all graft layers. IL-6, CXCL 10, IFNg, and nitrite plasmas levels showed
      behavior coincident with histopathology. Remarkably, allogeneic grafts showed a
      marked alteration of glucose absorptive capacity from POD 5 that was sustained
      until endpoint. Coincidently, barrier function alteration was evidenced by
      luminal ovalbumin translocation to serum. Contractile function was progressively
      impaired along ACR. Conclusions: Glucose absorption and barrier function are
      altered at early stages of ACR when histological alterations or gene expression
      changes were much subtle. This observation may provide simple evaluation tools
      that could be eventually translated to the clinics to contribute to early ACR
      diagnosis.

PMID- 29184910
TI  - Adapting the Surgical Apgar Score for Perioperative Outcome Prediction in Liver
      Transplantation: A Retrospective Study.
AB  - Background: The surgical Apgar score (SAS) is a 10-point scale using the lowest
      heart rate, lowest mean arterial pressure, and estimated blood loss (EBL) during
      surgery to predict postoperative outcomes. The SAS has not yet been validated in
      liver transplantation patients, because typical blood loss usually exceeds the
      highest EBL category. Our primary aim was to develop a modified SAS for liver
      transplant (SAS-LT) by replacing the EBL parameter with volume of red cells
      transfused. We hypothesized that the SAS-LT would predict death or severe
      complication within 30 days of transplant with similar accuracy to current
      scoring systems. Methods: A retrospective cohort of consecutive liver
      transplantations from July 2007 to November 2013 was used to develop the SAS-LT.
      The predictive ability of SAS-LT for early postoperative outcomes was compared
      with Model for End-stage Liver Disease, Sequential Organ Failure Assessment, and
      Acute Physiology and Chronic Health Evaluation III scores using multivariable
      logistic regression and receiver operating characteristic analysis. Results: Of
      628 transplants, death or serious perioperative morbidity occurred in 105
      (16.7%). The SAS-LT (receiver operating characteristic area under the curve
      [AUC], 0.57) had similar predictive ability to Acute Physiology and Chronic
      Health Evaluation III, model for end-stage liver disease, and Sequential Organ
      Failure Assessment scores (0.57, 0.56, and 0.61, respectively).Seventy-nine
      (12.6%) patients were discharged from the ICU in 24 hours or less. These
      patients' SAS-LT scores were significantly higher than those with a longer stay
      (7.0 vs 6.2, P < 0.01). The AUC on multivariable modeling remained predictive of
      early ICU discharge (AUC, 0.67). Conclusions: The SAS-LT utilized simple
      intraoperative metrics to predict early morbidity and mortality after liver
      transplant with similar accuracy to other scoring systems at an earlier
      postoperative time point.

PMID- 29184911
TI  - Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a
      Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides.
AB  - Background: Despite being the leading cause of graft failure, there is a lack of
      published data about the rates of rejection in kidney transplant patients with
      glomerulonephritis as the cause of end-stage renal disease. Methods: We examined
      all consecutive adult (>18 years) renal transplant recipients with biopsy-proven
      native renal glomerular disease who underwent kidney transplant between 1994 and
      2013. Glomerulonephritis groups included were IgA nephropathy (IgAN) (N = 306),
      focal segmental glomerulosclerosis (FSGS) (N = 298), membranous nephropathy (MN)
      (N = 81), and lupus nephritis (LN) (N = 177). Results: In the total cohort of 862
      patients, 363 patients had an episode of acute rejection during the follow-up
      period of 19 years (incidence rate of 7.2% per year). Forty-five of 81 patients
      with MN had an episode of acute rejection during the follow-up period. Patients
      with MN had significantly higher incidence of acute rejection (12.1 per 100
      person years, P < 0.05) in comparison to IgAN (7.2 per 100 person years), FSGS
      (7.4 per 100 person years), and LN (7.9 per 100 person years). Patients with MN
      had 1.9 times higher risk of developing acute rejection after transplant in
      comparison to IgAN (P < 0.005). In patients with MN, 33 of 45 (73.3%) rejection
      events were acute cellular rejection, 8 (17.8%) of 45 were acute antibody
      mediated rejection and 6 of 45 (13.3%) were combined cellular and antibody
      mediated acute rejection. Despite higher rates of acute rejection, 10-year
      allograft survival was similar in all subgroups. Conclusions: Patients with MN
      have higher incidence of acute rejection after kidney transplant but have similar
      10-year allograft survival in comparison to the other glomerular diseases like
      IgAN, FSGS, and LN.

PMID- 29184912
TI  - Liver Transplantation From Donors With a History of Malignancy: A Single-Center
      Experience.
AB  - Background: The demand for transplantable organs exceeds donor organ supply.
      Transplantation of organs from donors with a history of malignancy remains
      controversial and the transmission of cancer in liver transplant recipients has
      not been sufficiently examined. Methods: From 2002 until 2017, 83 livers from
      donors with a history of malignancy were transplanted at the University Hospital
      Essen, Germany. Donor and recipient data, type of malignancy, tumor-free interval
      at organ procurement, and follow-up data were analyzed. Results: Nine different
      tumor sites (central nervous system [n = 27], genitourinary [n = 24], breast [n =
      10], skin [n = 8], colorectal [n = 5], lung [n = 3], hemato-oncological [n = 3],
      thyroid [n = 2], and larynx [n = 1]) were detected in 83 donors. The majority
      (58%) of donors had tumor-free intervals of less than 5 years versus 19% of 6 to
      10 years versus 23% over 10 years. The risk of tumor transmission from donors was
      assessed as low in 44 (53%), intermediate in 28 (34%), and high in 11 (13%)
      cases. During median follow-up of 19.9 (0-155) months, none of the recipients
      developed donor-transmitted malignancy. Conclusions: Liver transplantation with
      organs from donors with a medical history of malignancy is feasible, and the risk
      of donor-transmitted malignancy appears to be low in this single-center analysis.
      A careful selection of donors remains mandatory and can expand the donor pool.

PMID- 29184914
TI  - Genomic links between blast exposure, brain injury, and Alzheimer disease.

PMID- 29184913
TI  - The Alzheimer's Disease Sequencing Project: Study design and sample selection.

PMID- 29184915
TI  - Laparoscopic Ureteral Reimplantation in Endometriosis: A Severe Case.
AB  - In aggressive cases, endometriosis can perturb the urogenital tract, in
      particular the ureter, which can potentially result in ureteral compression or
      stenosis. Even though this is rare, consequences are dramatic, such as
      hydronephrosis or organ failure. The present standard intervention comprises the
      resection of affected tissues and endometriosis foci combined with adjuvant
      hormonal therapy. When the ureter does not recover, ureteral reimplantation is
      required. The present case describes the successful laparoscopic approach of the
      reimplantation of the ureter with simultaneous cystoscopy.

PMID- 29184916
TI  - No Value of Routine Brain Computed Tomography 6 Weeks after Evacuation of Chronic
      Subdural Hematoma.
AB  - Background  The aim of this study was to evaluate the value of planned control
      postoperative brain computed tomography (CT) scan performed 4 to 6 weeks after
      the evacuation of chronic subdural hematoma. Materials and Methods  This
      retrospective study examined 202 patients who during a 2-year period from 2011
      and 2012 underwent surgical treatment for chronic subdural hematoma (CSDH).
      Information on patient age, sex, alcohol consumption, anticoagulant/antiplatelet
      treatment, history of head trauma, Glasgow coma scale (GCS), neurological
      symptoms, laterality of CSDH, and surgical technique was retrieved from patient
      charts. Results  Overall, 27 out of 202 patients had a recurrence of CSDH and re
      evacuation of the hematoma was performed. In all patients recurrence of
      neurological symptoms preceded the planned postoperative control brain CT 4 to 6
      weeks after primary surgery. Conclusion  Routinely postoperative control brain CT
      scan 4 to 6 weeks after the evacuation of a CSDH has no clinical value.

PMID- 29184917
TI  - Surgical Approach to Anorectal Melanoma with PET-CT Staging: A Case Report.
AB  - Rectal hemorrhage should be evaluated within a wide spectrum ranging from benign
      diseases to a malignant process. Especially, the melanomas of rectum are detected
      at an advanced stage when diagnosed since the present symptoms of rectal
      melanomas are similar. The question of what will be the surgical approach with
      MR, CT, and PET-CT imaging methods performed after histopathological diagnosis
      still conserves its topicality. PET-CT is a good imaging method for determination
      of distant metastasis and lymphatic involvement. In the present case, a patient
      with early-stage rectal melanoma was treated with APR. No relapse/metastasis was
      detected during the 18-month follow-up. The aggressive course of the disease and
      its low response rates to medical treatments may cause the surgical approaches to
      be more extensive.

PMID- 29184919
TI  - Why pregnenolone and progesterone, two structurally similar steroids, exhibit
      remarkably different cocrystallization with aromatic molecules.
AB  - Selective binding of steroid molecules is of paramount importance for designing
      drugs that can target the biological pathways of only individual steroids. From
      this perspective, it is remarkable that progesterone (PRO) and pregnenolone
      (PRE), two structurally similar steroids, demonstrate a dramatically different
      propensity to interact with aromatic molecules. It has been recently reported
      that, in solid-state cocrystallization, PRO forms cocrystals with a wide variety
      of aromatic systems whereas PRE cocrystallizes only with a few. In this work, a
      simple yet effective computational procedure was developed to explain the
      fundamental origins of this surprising phenomenon. This procedure enables a
      direct comparison of the strength of intermolecular binding in the structurally
      similar cocrystals of PRO and PRE by generating experimentally inaccessible meta
      stable cocrystals of PRE that closely resemble those observed for PRO. Direct
      comparative analysis shows that interactions between the alpha-face of the
      steroid and the pi-electrons of aromatic molecules, the focus of previous
      studies, are not sufficiently different to explain the cocrystallization behavior
      of PRO and PRE. Instead, the observed difference is attributed to the different
      stabilities of the cocrystals relative to their pure components: organic and
      steroid crystals. It is calculated that the cocrystallization process is
      thermodynamically favorable in the case of PRO and unfavorable in the case of
      PRE. Furthermore, strong hydrogen bonds in the pure PRE crystal appear to be the
      major factor that makes the cocrystallization of PRE energetically unfavorable
      for a wide range of aromatic molecules. The fundamental analysis performed in
      this work has important practical implications for designing new steroid
      containing crystals, selective biomolecular steroid receptors, and steroid
      specific drugs. It suggests that a strategy for the selective binding of steroids
      should focus primarily on tuning the strength of hydrogen bonding.

PMID- 29184918
TI  - New evidence of mating swarms of the malaria vector, Anopheles arabiensis in
      Tanzania.
AB  - Background: Malaria mosquitoes form mating swarms around sunset, often at the
      same locations for months or years. Unfortunately, studies of Anopheles swarms
      are rare in East Africa, the last recorded field observations in Tanzania having
      been in 1983. Methods: Mosquito swarms were surveyed by trained volunteers
      between August-2016 and June-2017 in Ulanga district, Tanzania. Identified
      Anopheles swarms were sampled using sweep nets, and collected mosquitoes killed
      by refrigeration then identified by sex and taxa. Sub-samples were further
      identified by PCR, and spermatheca of females examined for mating status.
      Mosquito ages were estimated by observing female ovarian tracheoles and rotation
      of male genitalia. GPS locations, types of swarm markers, start/end times of
      swarming, heights above ground, mosquito counts/swarm, and copulation events were
      recorded. Results: A total of 216 Anopheles swarms were identified, characterized
      and mapped, from which 7,142 Anopheles gambiae s.l and 13 Anopheles funestus were
      sampled. The An. gambiae s.l were 99.6% males and 0.4% females, while the An.
      funestus were all males. Of all An. gambiae s.l analyzed by PCR, 86.7% were An.
      arabiensis, while 13.3% returned non-amplified DNA. Mean height (+/-SD) of swarms
      was 2.74+/-0.64m, and median duration was 20 (IQR; 15-25) minutes. Confirmed
      swarm markers included rice fields (25.5%), burned grounds (17.2%), banana trees
      (13%), brick piles (8.8%), garbage heaps (7.9%) and ant-hills (7.4%). Visual
      estimates of swarm sizes by the volunteers was strongly correlated to actual
      sizes by sweep nets (R=0.94; P=<0.001). All females examined were nulliparous and
      95.6% [N=6787] of males had rotated genitalia, indicating sexual maturity.
      Conclusions: This is the first report of Anopheles swarms in Tanzania in more
      than three decades. The study demonstrates that the swarms can be identified and
      characterized by trained community-based volunteers, and highlights potential new
      interventions, for example targeted aerosol spraying of the swarms to improve
      malaria control.

PMID- 29184920
TI  - Functionalized gold nanoparticle-enhanced competitive assay for sensitive small
      molecule metabolite detection using surface plasmon resonance.
AB  - The development of sensing systems for the measurement of small molecules is an
      active area of research. A sensor based approach for the measurement of
      metabolites can potentially provide the simplicity and portability required for
      widespread use. Rapid detection and quantitation of small-molecule metabolites
      can potentially emerge as an effective way to link the metabolite profile to the
      disease state. Surface plasmon resonance (SPR) combined with molecular
      recognition elements to deliver high specificity is a sensing platform that has
      been widely applied for a large range of biomolecules. However, direct detection
      of small molecules with SPR challenges the refractive index based detection
      mechanism. The work described here combines a periplasmic binding protein for
      recognition with target modified gold nanoparticles (AuNPs) in a competitive
      assay format for folic acid (FA) detection. Specifically, a SPR imaging substrate
      containing immobilized folate binding protein (FBP) is used to measure the
      adsorption of FA conjugated AuNPs. The immobilization of the FBP and the binding
      of the FA conjugated AuNPs are characterized and optimized. It is shown that free
      FA in solution can be quantitatively measured by competition for the surface
      binding sites with the functionalized AuNPs. We demonstrate that the dynamic
      range can be lowered from micromolar to nanomolar by simply decreasing the
      concentration of FA conjugated AuNPs, thus lowering the limit of detection to 2.9
      nM. This type of competitive assay can be applied to a range of small molecules,
      which paves the way for future multiplexed analysis of metabolites using SPR.

PMID- 29184921
TI  - The effects of glycine, TMAO and osmolyte mixtures on the pressure dependent
      enzymatic activity of alpha-chymotrypsin.
AB  - High pressure is an important feature of certain natural environments, such as
      the deep sea where pressures up to about 1000 bar are encountered. Further,
      pressure effects on biosystems are of increasing interest for biotechnological
      applications, such as baroenzymology. We studied the effect of two different
      natural osmolyte mixtures, with major components being glycine and trimethylamine
      N-oxide (TMAO), on the activity of alpha-chymotrypsin, using high-pressure
      stopped-flow methodology in combination with fast UV/Vis detection. We show that
      pressure is not only able to drastically enhance the catalytic activity and
      efficiency of the enzyme, but also that glycine has a significant and diverse
      effect on the enzymatic activity and volumetric properties of the reaction
      compared to TMAO. The results might not only help to understand the modulation of
      enzymatic reactions by natural osmolytes, but also elucidate ways to optimize
      enzymatic processes in biotechnological applications.

PMID- 29184922
TI  - The impact of metal complex lipids on viscosity and curvature of hybrid
      liposomes.
AB  - A morphology transformation of hybrid liposomes was shown to occur from spherical
      vesicles to tubular micelles when increasing the ratio of the metal complex lipid
      present. Phase transition temperatures increased while viscosities decreased,
      indicating that the hybrids exhibit stronger interaction between heads but weaker
      interaction between alkyl chains than occurs in pristine liposomes.

PMID- 29184923
TI  - Controlling N2O formation during regeneration of NOx storage and reduction
      catalysts: from impact of platinum-group metal type to rational utilization.
AB  - Herein, we report an effective strategy for minimization of N2O emissions based
      on elucidating the impact of the type of platinum-group metals (PGMs = Pt, Pd, or
      Rh) on by-product formation during regeneration of PGM-BaO/Al2O3 catalysts. The
      significant differences in N2O or NH3 formation were thoroughly investigated from
      the perspective of an in situ reaction. Kinetic analysis of NO reduction by CO
      shows different turnover frequency and apparent activation energy values over
      these catalysts. The results reveal that the apparent kinetics is dependent on
      the type of platinum-group metal chosen. In situ DRIFTS data indicate that the
      unique adsorption behaviors of reactants via which they access each PGM
      essentially determine their individual reaction kinetics. The preferential
      adsorption of NO or CO molecules on the PGM surface controls the dominant
      intermediate (NOad/Nad, COad, or NCOad) species, which is a major factor
      responsible for various yields of N2O and NH3 during the rich period. Finally, a
      feasible strategy has been proposed via optimizing catalyst formulation to
      effectively control the N2O emissions.

PMID- 29184924
TI  - 5-(Hydroxymethyl)uracil and -cytosine as potential epigenetic marks enhancing or
      inhibiting transcription with bacterial RNA polymerase.
AB  - DNA templates containing 5-hydroxymethyluracil or 5-hydroxymethylcytosine were
      used in an in vitro transcription assay with RNA polymerase from Escherichia
      coli. A strong enhancement of transcription was observed from DNA containing the
      Pveg promoter whereas a decrease was observed from DNA containing the rrnB P1
      promoter, suggesting that they may act as epigenetic marks.

PMID- 29184925
TI  - Light-driven nanofiber and nanoring morphological transformations in organogels
      based on an azobenzene-bridged biscalix[4]arene.
AB  - The morphologies of an azobenzene-bridged biscalix[4]arene organogel in different
      organic solvents can be photo-reversibly switched between nanofibers and
      nanorings as well as between closed and open-form vesicles.

PMID- 29184926
TI  - State-to-state mode specificity in H + DOH(nuOH = 1) -> HD + OH(nu2 = 0)
      reaction: vibrational non-adiabaticity or local-mode excitation?
AB  - It is well established that chemical reactions often involve only a small number
      of atoms near the reaction site, and the remainder of the reactant molecules are
      mostly spectators. It is thus of great importance to understand the role played
      by the active as well as spectator modes in chemical dynamics. In this work, we
      examine in great detail the influence of reactant modes on the reactivity and
      product state distribution, using a four-atom prototypical reaction as the
      example. State-of-the-art full-dimensional state-to-state quantum dynamics reveal
      a startling observation in which the DOH(nuOH = 1) molecule reacts with a H atom
      to produce a vibrationless OH product. This is surprising because OH is
      considered as a spectator in this reaction and its internal energy should be
      sequestered throughout the reaction. By careful analysis within the local-mode
      regime, we demonstrate that the surprising reactivity is not due to vibrational
      non-adiabaticity during the reaction. Rather, it can be attributed to a small OD
      excited local-mode component in the reactant wavefunction. The quantum state
      resolved dissection of this prototype reaction helps to advance our understanding
      of larger reactive systems.

PMID- 29184927
TI  - Construction of luminescent high-nuclearity Zn-Ln rectangular nanoclusters with
      flexible long-chain Schiff base ligands.
AB  - Three Zn-Ln clusters [Ln8Zn6(L1)2(OAc)20(O)2(NO3)4(OH)4] (Ln = Sm (1) and Nd (2))
      and [Nd4Zn4(L2)2(OAc)10(NO3)2(OH)4] (3) were prepared using two long-chain Schiff
      base ligands. The Zn-Ln clusters exhibit interesting nano-square-like structures.
      Their visible and NIR luminescence properties were investigated.

PMID- 29184928
TI  - C-S bond induced ultrafine SnS2 dot/porous g-C3N4 sheet 0D/2D heterojunction:
      synthesis and photocatalytic mechanism investigation.
AB  - The construction of novel heterojunctions is precisely deemed to be an effective
      strategy to facilitate photo-generated carrier separation and boost charge
      utilization efficiency, leading to much enhanced photocatalytic activities.
      Herein, in situ of growing ultrafine SnS2 nanoparticles on a porous g-C3N4 sheet
      (SnS2/g-C3N4) 0D/2D heterojunction was achieved via a low-temperature
      solvothermal process. Combined with various characterization techniques, it is
      revealed that SnS2 dots with a diameter of 3 nm distribute evenly on the surface
      of the g-C3N4 substrate with strong C-S bonds. The photocatalytic activities are
      evaluated by the degradation of Rhodamine B (RhB) under visible light
      irradiation, showing a much enhanced photodegradation efficiency of 96.8% over
      105 min irradiation and an enhanced reaction rate constant (k = 3.3% min-1, 8.25
      and 8.05 times that of pure g-C3N4 and SnS2). The improved photocatalytic
      activities could be ascribed to the efficient electron-hole separation of porous
      g-C3N4, which is caused by the ultrafine SnS2 dots linked with the g-C3N4
      substrate through C-S bonds. Therefore, the recombination efficiency is
      decreased. In addition, reactive active species trapping experiments prove that
      the superoxide radical (O2-) and holes (h+) are the main active species in this
      photocatalytic system. The photodegradation mechanism of the SnS2/g-C3N4
      heterojunction is analyzed and demonstrated in detail.

PMID- 29184929
TI  - Embedding liquid lasers within or around aqueous microfluidic droplets.
AB  - In this paper, we demonstrate the incorporation of dye-based liquid lasers within
      or around flowing aqueous microfluidic droplets. In particular, we use dye
      solutions in benzyl alcohol, and either disperse an ensemble of small (~20 MUm)
      lasing droplets within large (~500 MUm) aqueous droplets flowing in a simple
      glass capillary-based microfluidic device, or 'wrap' a thin (~10 MUm) lasing
      benzyl alcohol shell around larger (~560 MUm) microfluidic aqueous droplets. We
      experimentally and theoretically characterize the lasing behavior in both cases,
      which is supported by whispering-gallery mode (WGM) optical resonances at the
      droplet interfaces. We showcase a simple application of our method, which
      highlights the advantages of having embedded, spatially segregated laser sources
      within a droplet containing a model analyte solution. With this method, each
      microfluidic droplet now functions not only as an isolated experiment flask, but
      is also capable of on drop sensing that exploits WGM-based lasing, thus expanding
      the possibilities for online monitoring of biophysical/biochemical processes and
      sensitive detection of biomolecules in droplet-based microfluidics.

PMID- 29184930
TI  - Bimetallic Ru(ii) and Os(ii) complexes based on a pyrene-bisimidazole spacer:
      synthesis, photophysics, electrochemistry and multisignalling DNA binding studies
      in the near infrared region.
AB  - We report in this paper the synthesis, characterization, photophysical and
      electrochemical properties, and detailed DNA binding affinities of two
      homobimetallic Ru(ii) and Os(ii) complexes derived from a new bridging ligand
      consisting of two pyridyl-imidazole coordinating units rigidly coupled with a
      central pyrene moiety. The structure of the diruthenium complex was confirmed by
      X-ray crystallography. Both complexes exhibit luminescence at room temperature
      from their 3MLCT states, with lifetimes of tau1 = 12.6 ns and tau2 = 48.8 ns for
      the Ru(ii) complex (1) and tau1 = 23.7 ns for the Os(ii) complex (2). For 2, the
      luminescence maximum stretches to the NIR region, which is suitable for potential
      biological applications. Both complexes exhibit two successive one-electron
      reversible metal-centered oxidations in the positive potential window.
      Computational studies employing DFT and TD-DFT methods were also performed to
      assign the experimentally observed optical spectral bands in the complexes. The
      binding affinities of the complexes towards DNA were thoroughly investigated
      through a variety of techniques, viz. absorption, luminescence, excited state
      lifetime, circular dichroism, thermal denaturation, viscosity measurement, and
      relative DNA binding studies using ethidium bromide. Finally, molecular docking
      studies were also carried out to visualize the modes of interaction between the
      complexes and DNA.

PMID- 29184931
TI  - Separation of proteins from complex bio-matrix samples using a double
      functionalized polymer monolithic column.
AB  - A double-functionalized polymer monolithic column was fabricated within the
      confines of a stainless-steel column (50 mm * 4.6 mm i.d.) via a facile method
      using iron porphyrin, ionic liquid (1-allyl-3-methylimidazolium chloride) and
      1,10-decanediol dimethacrylate as tri-monomers; ethylene dimethacrylate as a
      crosslinker; polyethylene glycol 400 and N,N-dimethylformamide as co-porogens;
      benzoyl peroxide and N,N-dimethyl aniline as the redox initiation system. Results
      obtained from scanning electron microscopy, nitrogen adsorption-desorption, and
      mercury intrusion porosimetry confirmed the uniform pore structure and the pore
      size distribution of macro-pores. The home-made monolith was further
      characterized by elemental analysis to investigate the elemental composition of
      Fe supplied by iron porphyrin, confirming the synthetic process. The resulting
      optimized monolithic column was used as the stationary phase in high performance
      liquid chromatography for separating proteins, such as mixture of standard
      proteins, egg white, and human plasma, exhibiting good selectivity and high
      performance. It is worth noting that the home-made double-functionalized polymer
      monolithic column shows excellent selectivity for fractionation separation of
      human plasma proteins, and it is a promising separation tool for complex bio
      samples in proteomic research.

PMID- 29184932
TI  - Water-soluble small-molecule probes for RNA based on a two-photon fluorescence
      "off-on" process: systematic analysis in live cell imaging and understanding of
      structure-activity relationships.
AB  - The conveniently obtained water-soluble small-molecule L1-5 were selective for
      RNA with remarkable "off-on" two-photon fluorescence responses in vitro and in
      vivo, showing that L1-5 can surprisingly stain mitochondria or nucleoli
      individually with orange fluorescence under different focal lengths. Compounds L6
      8 were prepared, for comparison, to further explore the mechanism of the binding
      of L1-5 with RNA, which revealed that the synergistic effect of the amino group
      and the pyridinium cation played a significant role in distinct cell imaging.

PMID- 29184933
TI  - Anionic indabenzene: synthesis and characterization.
AB  - An anionic indabenzene was synthesized via the transmetallation of an
      aluminacyclohexadiene with bulky silyl substituents, and fully characterized
      using multinuclear NMR spectroscopy and X-ray crystallography. The observed
      structural features are consistent with the formal criteria of aromaticity.
      Additionally, the results of DFT calculations suggested contributions from an
      ambiphilic resonance structure, similar to the corresponding aluminum and gallium
      derivatives.

PMID- 29184934
TI  - Extracellular vesicles, exosomes and shedding vesicles in regenerative medicine -
      a new paradigm for tissue repair.
AB  - Tissue regeneration by stem cells is driven by the paracrine activity of shedding
      vesicles and exosomes, which deliver specific cargoes to the recipient cells.
      Proteins, RNA, cytokines and subsequent gene expression, orchestrate the
      regeneration process by improving the microenvironment to promote cell survival,
      controlling inflammation, repairing injury and enhancing the healing process. The
      action of microRNA is widely accepted as an essential driver of the regenerative
      process through its impact on multiple downstream biological pathways, and its
      ability to regulate the host immune response. Here, we present an overview of the
      recent potential uses of exosomes for regenerative medicine and tissue
      engineering. We also highlight the differences in composition between shedding
      vesicles and exosomes that depend on the various types of stem cells from which
      they are derived. The conditions that affect the production of exosomes in
      different cell types are deliberated. This review also presents the current
      status of candidate exosomal microRNAs for potential therapeutic use in
      regenerative medicine, and in applications involving widely studied organs and
      tissues such as heart, lung, cartilage and bone.

PMID- 29184935
TI  - In situ synthesis of Bi nanoflakes on Ni foam for sodium-ion batteries.
AB  - We report a facile method to in situ synthesize Bi nanoflakes on Ni foam (Bi/Ni)
      via a replacement reaction, which can directly work as an anode for sodium-ion
      batteries (SIBs) without further treatment. The integrated nanoflake structure of
      the Bi/Ni effectively accommodates the dramatic volume changes of Bi during
      cycling, and favors both electron and Na+ transport through the electrode. This
      ensures high cycling performance and good rate capability. The
      sodiation/desodiation of Bi is revealed to be composed of two successive steps:
      Bi <-> NaBi and NaBi <-> Na3Bi. This facile strategy will encourage more
      investigations into the design and synthesis of integrated electrodes for high
      performance SIBs.

PMID- 29184936
TI  - The shape of the electronic circular dichroism spectrum of (2,6
      dimethylphenyl)(phenyl)methanol: interplay between conformational equilibria and
      vibronic effects.
AB  - Comparison between chiroptical spectra and theoretical predictions is the method
      of choice for the assignment of the absolute configuration of chiral compounds in
      solution. Here we report the case of an apparently simple biarylcarbinol, whose
      electronic circular dichroism (ECD) in the 1Lb region exhibits a peculiar
      alternation of negative and positive bands. Adopting Density Functional Theory,
      and describing solvent effects with implicit methods, we found three stable
      conformers in ethanol, each of them with two close lying states corresponding to
      similar local 1Lb excitations on the two phenyls. We computed the corresponding
      vibronic ECD spectra in harmonic approximation, including Duschinsky mixings as
      well as both Franck Condon (FC) and Herzberg Teller (HT) effects. Exploiting a
      recently developed mixed quantum/classical method, we further investigated the
      contribution of the vibronic spectra of out-of-equilibrium structures along the
      interconversion path connecting the different conformers. In this way, we
      achieved a reasonable agreement with experiment and attributed the alternating
      signs of the bands to the existence of different conformers. The remaining
      discrepancies with experiment indicate that specific solute-solvent interactions
      modulate the relative conformers' stabilities, calling for new methods able to
      combine Molecular Dynamics explorations and vibronic calculations. Moreover, the
      poor performance of HT approaches and the existence of two closely-lying states
      suggest the necessity of an improved fully-nonadiabatic vibronic approach. These
      findings demonstrate that even for such a simple system as the biarylcarbinol
      investigated here, a full reproduction of the fine details of the ECD spectrum
      requires the development of new improved methods.

PMID- 29184937
TI  - Decreased domain size of p-DTS(FBTTh2)2/P(NDI2OD-T2) blend films due to their
      different solution aggregation behavior at different temperatures.
AB  - Nanoscale interpenetrating networks play a key role in determining the
      optoelectrical properties of functional blends. However, phase separated large
      domain sizes could probably be observed in pristine films composed of two
      crystalline components. For example, p-DTS(FBTTh2)2/P(NDI2OD-T2) 3/2 blend films
      with interpenetrating networks are obtained, however, large domain sizes are
      found when they are prepared from a 20  degrees C solution due to the
      simultaneous process of crystallization and phase separation during solvent
      evaporation. In this paper, we proposed to reduce the domain size of p
      DTS(FBTTh2)2/P(NDI2OD-T2) blend films using their different solution aggregation
      behaviors at different temperatures. The aggregation of p-DTS(FBTTh2)2 molecules
      in chlorobenzene (CB) was insensitive to the solution temperature. However, the
      in situ absorption spectra of the neat P(NDI2OD-T2) solution from 80  degrees C
      to room temperature indicated that P(NDI2OD-T2) aggregation increased with
      decreasing temperature due to intrachain interactions. Therefore, in order to
      reduce the domain size, we employed a hot solution to prepare the blend films.
      During the solidification process, the majority of p-DTS(FBTTh2)2 molecules were
      confined in the P(NDI2OD-T2) networks prior to occurrence of severe p
      DTS(FBTTh2)2 aggregation. Thus, the domain size of the p-DTS(FBTTh2)2 phase
      became smaller than that of the pristine films, leading to a decrease in the
      corresponding photoluminescence intensity of the blend films. In addition, the
      crystallinity of the blend films improved after thermal annealing, which resulted
      from the ordered alignment of p-DTS(FBTTh2)2 molecules facilitated by their
      enhanced diffusion ability. Based on the various morphologies, a possible phase
      diagram of the p-DTS(FBTTh2)2/P(NDI2OD-T2) blend system was depicted, which could
      be a guide to directly control the morphology of blend films.

PMID- 29184939
TI  - Consumption of plant food supplements in the Netherlands.
AB  - The use of food supplements containing herbs or other botanical ingredients
      (plant food supplements, PFS) is on the rise. In some cases, PFS can contain
      compounds that are toxic and may pose a health risk. To assess the potential
      health risks, information on the consumption of PFS is required, however, this
      was lacking for the Netherlands. In the current study, the consumption of PFS was
      investigated for several subgroups in the Dutch population, including children.
      Data from the Dutch National Food Consumption Surveys were used to get a first
      impression on the consumption of PFS. To obtain more detailed information, a
      specific PFS consumption survey was performed using online questionnaires. First,
      a screening survey was performed among a representative sample of 75 100 adults
      and children of the Dutch population, followed by a main survey among 739
      selected PFS users in eight different age and gender subgroups. The prevalence of
      PFS users in the Dutch population was approximately 10% for men, 17% for women
      and 13% for children. A wide variety of PFS was used, with around 600 different
      PFS reported, containing 345 different botanicals. The most frequently used
      botanicals were echinacea (Echinacea purpurea), ginkgo (Ginkgo biloba), cranberry
      (Vaccinium macrocarpon), ginseng (Panax ginseng) and algae (such as species
      belonging to the genus Spirulina or Chlorella). Because PFS are widely used in
      the Dutch population, it is important to evaluate the potential risks associated
      with PFS consumption in the Netherlands, including potential herb-drug
      interactions. The data collected in this study are of great value to assess these
      risks.

PMID- 29184938
TI  - Minocycline hydrochloride loaded on titanium by graphene oxide: an excellent
      antibacterial platform with the synergistic effect of contact-killing and release
      killing.
AB  - Titanium and its alloys have been widely used in orthopedic and dental implants
      because of their excellent properties. However, implant failures still occur due
      to implant-associated bacterial infections. Therefore, proper surface
      modification of titanium and its alloys is necessary. In this work, commercial
      pure titanium plates were modified with graphene oxide (GO) which was used to
      load minocycline hydrochloride. Gram-positive Staphylococcus aureus (S. aureus)
      and Streptococcus mutans (S. mutans) and Gram-negative Escherichia coli (E. coli)
      were used to investigate the antibacterial activity of the samples. Human
      gingival fibroblast (HGF) cells were applied to assess the cytocompatibility of
      the various samples. To investigate cell adhesion and cell surface coverage in
      the presence of bacteria, the coculture of HGF cells and S. aureus was performed.
      The results indicated that the GO-modified titanium surface could inhibit the
      growth of the bacteria which had direct contact with GO, while it could not
      affect the bacteria without direct contact of GO. Minocycline hydrochloride on
      the GO-modified titanium surface (M@GO-Ti) showed a slow release behavior and
      exhibited excellent antibacterial activity with the synergistic effect of contact
      killing and release-killing by GO and minocycline hydrochloride, respectively. In
      the coculture process with the presence of S. aureus, HGF cells on M@GO-Ti
      demonstrated the best cell viability and cell surface coverage among all the
      samples.

PMID- 29184940
TI  - Constructing CrIII-centered heterometallic complexes: [NiCrIII] and [CoCrIII]
      wheels.
AB  - The solvothermal reaction between Cr(acac)3, MCl2.6H2O (M = Ni, Co) and 2-hydroxy
      4-methyl-6-phenyl-pyridine-3-amidoxime (H2L), under basic conditions, led to the
      synthesis of the heterometallic heptanuclear clusters [MCr(HLzw)6(HL)6].3Cl (M =
      Ni, 1; Co, 2), with the nickel analogue displaying an S = 9/2 spin ground-state.

PMID- 29184941
TI  - Syntheses, structures, and magnetic properties of two unique Cu(ii)-based
      coordination polymers involving a crystal-to-crystal structural transformation
      from a 1D chain to a 3D network.
AB  - Two new coordination polymers, Cu(Hbsal)2(4,4'-bpy)2 (1) and Cu(bsal)(4,4'
      bpy).DMF (2), have been synthesized from 5-bromosalicylic acid (H2bsal) and the
      auxiliary ligand 4,4'-bipyridine (4,4'-bpy) through a slow diffusion method.
      Compound 1 is composed of parallel 1D linear chains, whereas compound 2
      represents a non-interpenetrated 3D sod net which is constructed from left and
      right-handed helical chains alternately separated by 4,4'-bpy. The most
      interesting finding is that compound 1 can be irreversibly transformed into 2 in
      a crystal-to-crystal manner in the case that compound 1 is immersed in the DMF
      solvent. Particularly, the 1D-to-3D crystal-to-crystal structural transformation
      also incurs a drastic change in the magnetic properties of 1 and 2.

PMID- 29184942
TI  - Bone-targeting poly(ethylene sodium phosphate).
AB  - Poly(ethylene sodium phosphate) (PEP.Na) showed excellent cytocompatibility and
      in vivo bone affinity. Moreover, PEP.Na did not interact with thrombin, which is
      a coagulation-related protein. Because immobilization of therapeutic agents and
      imaging probes on PEP.Na is easily performed, PEP.Na is a promising polymer for
      bone-targeted therapies.

PMID- 29184943
TI  - Interception of amide ylides with sulfonamides: synthesis of (E)-N-sulfonyl
      amidines catalyzed by Zn(OTf)2.
AB  - Through the interception of amide ylides with sulfonamides, we herein report the
      first general example of an intermolecular condensation reaction between
      sulfonamides and amides. Beyond formamides, this approach was successfully
      applied to a variety of lactams and linear amides, giving rise to a broad array
      of (E)-N-sulfonyl amidines.

PMID- 29184944
TI  - Improving the SMM and luminescence properties of lanthanide complexes with LnO9
      cores in the presence of ZnII: an emissive Zn2Dy single ion magnet.
AB  - Mononuclear complexes of stoichiometry [Ln(H3L)(H2O)(NO3)](NO3)2 (Ln = Tb, 1; Dy,
      2, Er, 3), which crystallise with different solvates, and the heterotrinuclear
      compound [Zn2Dy(L)(NO3)3(OH)] (4) can be obtained with the same H3L compartmental
      ligand. The single X-ray crystal structure of the mononuclear complexes shows a
      LnO9 core with a muffin-like disposition while the geometry of the DyO9 core in 4
      seems to be closer to spherical capped square antiprism. The analysis of the
      magnetic properties of all the complexes demonstrates that the mononuclear
      lanthanide compounds do not show slow relaxation of the magnetization, even when
      the samples are diluted with a diamagnetic matrix and subjected to a dc applied
      field of 1000 Oe. Nevertheless, the heterotrinuclear dysprosium complex 4.3H2O is
      a field-induced single ion magnet, with an estimated Ueff barrier of 59 K. The
      luminescence characterisation of all the metal complexes in methanol solution at
      298 K also shows a notable increase in the fluorescence emission of the
      heterotrinuclear complex with respect to the mononuclear ones, in such a way that
      4 can be defined as a fluorescent single ion magnet.

PMID- 29184945
TI  - Carbon adsorption on doped cementite surfaces for effective catalytic growth of
      diamond-like carbon: a first-principles study.
AB  - We studied the adsorption of carbon on (100), (010) and (001) surfaces of alloyed
      cementite (Fe2MC with M = Cr, Mn, Mo, Ni and V), in comparison with that of
      cementite (Fe3C), to predict the catalytic effect of the element-doped cementite
      on diamond-like carbon (DLC) growth through first-principles analysis. The
      adsorption of carbon on the alloyed cementite surface is related to its surface
      stability. The more stable a surface, the weaker its adsorption capability. Mn,
      Mo, Cr or V alloyed cementite have a higher adsorption energy than unalloyed
      cementite. A correlation has also been found between the adsorption and the
      transferred charge based on Bader charge analysis. Among all the types of doped
      cementite under study, Fe2NiC possesses the strongest catalytic activity for DLC
      growth based on the formation energy of diamond carbon. Doping cementite with the
      appropriate elements provides a promising means to improve the catalytic activity
      of Fe3C for effective DLC growth.

PMID- 29184946
TI  - Hydrogen-free reductive amination using iron pentacarbonyl as a reducing agent.
AB  - We developed solvent-free reductive amination without an external hydrogen source
      using iron pentacarbonyl as a reducing agent. Neither a catalyst nor any other
      additives were employed. Various types of substrates are suitable for the
      reaction, including those with low reactivity, e.g. benzophenone. Among others,
      the protocol tolerates bromo-, cyano-, benzyloxy-, pyrimidyl and styryl moieties.

PMID- 29184947
TI  - A general strategy for the synthesis of indoloquinolizine alkaloids via a cyanide
      catalyzed imino-Stetter reaction.
AB  - A new strategy applicable to the synthesis of indoloquinolizine natural products
      has been developed. A cyanide-catalyzed intramolecular imino-Stetter reaction of
      aldimines, derived from 2-aminocinnamic acid derivatives and 2
      pyridinecarboxaldehydes, provided indole-3-acetic acid derivatives bearing a
      pyridyl ring at the 2-position. Reduction of the carboxylic acid moiety to an
      alcohol followed by activation of the resulting alcohol with Tf2O or TsCl
      generated indoloquinolizinium salts, which were utilized as precursors for
      indoloquinolizine natural products. The advantage of this protocol was
      successfully demonstrated in the total syntheses of arborescidine A and
      nauclefidine.

PMID- 29184948
TI  - Layered double hydroxide anchored ionic liquids as amphiphilic heterogeneous
      catalysts for the Knoevenagel condensation reaction.
AB  - In recent years, great attention has been dedicated to the development of
      heterogeneous base catalysts providing a green and sustainable process in benign
      aqueous media. Herein, the ionic liquid modified layered double hydroxide (LDH)
      based catalysts of LDH-IL-Cn (n = 4, 8, 12) were prepared by adopting an
      exfoliation/assembly strategy, in which the ionic liquids (ILs) were covalently
      anchored onto the surface of LDH layers. The resulting LDH-IL-Cn were
      characterized by FT-IR, solid-state 13C NMR, 29Si CP/MAS NMR, 27Al-MAS NMR, XRD,
      TG-DTA, BET, XPS, SEM, CO2-TPD, contact angle experiments, etc. The catalytic
      performance of LDH-IL-C12 for the Knoevenagel condensation of a variety of
      aldehydes with ethyl cyanoacetate/malononitrile in H2O at room temperature showed
      excellent yields and selectivities. Moreover, the base catalyst of LDH-IL-C12 can
      be easily recycled and reused for at least 5 times without the decrease of its
      catalytic efficiency. The scaled-up experiments revealed that the catalyst
      retained its efficiency and robustness.

PMID- 29184949
TI  - Twisted MX2/MoS2 heterobilayers: effect of van der Waals interaction on the
      electronic structure.
AB  - A comprehensive first-principles study of the electronic properties of twisted 2D
      transition metal dichalcogenide (TMDC) heterobilayers MX2/MoS2 (M = Mo, Cr, W; X
      = S, Se) with different rotation angles has been performed. The van der Waals
      (vdW) interaction is found to have an important effect on the electronic
      structure of two-dimensional (2D) TMDC heterobilayers. Compared to non-twisted
      heterobilayers, the interlayer distance of twisted heterobilayers increases
      appreciably, thereby changing the vdW interaction of the heterobilayers as well
      as the electronic structure of the MX2/MoS2 systems. As a result, for CrSe2/MoS2
      and MoSe2/MoS2 systems, the indirect bandgap (Gamma-K) exhibits a notable
      enlargement (about 0.1 eV), leading to the indirect-to-direct gap transition. At
      twisting angles between 13.2 degrees  and 46.8 degrees , the interlayer distance
      is nearly constant for the mismatched lattices over the entire sample, resulting
      in nearly the same electronic structure. Even after considering the spin-orbit
      coupling (SOC) effect, the indirect-to-direct transition is still predicted to
      occur in the WS2/MoS2 heterobilayer due to the large spin-orbit splitting.

PMID- 29184950
TI  - Gold nanoparticle-based nano-probe for the colorimetric sensing of Cr3+ and
      Cr2O72- by the coordination strategy.
AB  - In this work, an N-T/gold nanoparticle system was assembled for the convenient
      and colorimetric identification of Cr based on its coordination chemistry with
      the thymine derivative (N-T). In addition to the visible colorimetric changes for
      the qualitative Cr identification, the A630 nm/520 nm values changed linearly
      with Cr concentration over a range of 0.5-2.5 MUM and the detection limits
      reached 0.03 MUM and 0.07 MUM for Cr3+ and Cr2O72-, respectively, both of which
      satisfied the Cr water quality standards of the U.S. EPA, WHO and China.
      Furthermore, a more convenient method was developed for quantitative
      determination of Cr concentrations in practical samples based on the Eyedropper
      function in Microsoft's PowerPoint software, wherein the RGB (red, green and
      blue) value of the sample could be easily screened in the colorimetric card for a
      more accurate result with good recovery, avoiding complicated instrumentation.

PMID- 29184951
TI  - Rattler-induced aging dynamics in jammed granular systems.
AB  - Granular materials jam when developing a network of contact forces able to resist
      the applied stresses. Through numerical simulations of the dynamics of the
      jamming process, we show that the jamming transition does not occur when the
      kinetic energy vanishes. Rather, as the system jams, the kinetic energy becomes
      dominated by rattler particles, which scatter within their cages. The relaxation
      of the kinetic energy in the jammed configuration exhibits a double power-law
      decay, which we interpret in terms of the interplay between backbone and rattler
      particles.

PMID- 29184952
TI  - Interfacial assembly and hydrolysis for synthesizing a TiO2/metal-organic
      framework composite.
AB  - Herein we propose an interfacial assembly and hydrolysis route for fabricating
      TiO2/UiO-67 composites. The UiO-67 assembles at the water-oil interface serving
      as a stabilizer of the emulsion. TiO2 nanoparticles are loaded on UiO-67 by
      hydrolysis of the precursor TBT (tetra-n-butyl titanate) at the water-oil
      interface. By such a strategy, hollow capsules structured by UiO-67 and decorated
      by ultra-small TiO2 nanoparticles were produced. The newly-constructed composite
      combines the CO2 adsorption properties of UiO-67 and the photocatalytic activity
      of TiO2, showing high activity for the photocatalytic reduction of CO2 to formic
      acid. Such a composite with a novel structure provides a promising route for the
      preparation of new compound materials.

PMID- 29184953
TI  - A one pot three-component reaction for the preparation of dihydroquinolines with
      two different ketones and aromatic amines.
AB  - A three component reaction with two different ketones and aromatic amines was
      firstly investigated. The difference in reactivity between ordinary ketones and
      ketone esters allowed for the production of 1,2-DHQs efficiently. The possible
      Skraup reaction with 2 equiv. of the same ketones was prohibited due to the fast
      formation of imines.

PMID- 29184954
TI  - Reversible modification of DNA by methyltransferase-catalyzed transfer and light
      triggered removal of photo-caging groups.
AB  - Methyltransferases are powerful tools for site-specific transfer of non-natural
      functional groups from synthetic analogs of their cosubstrate S-adenosyl-l
      methionine (AdoMet). We present a new class of AdoMet analogs containing photo
      caging (PC) groups in their side chain, enzymatic transfer of PC groups by a
      promiscuous DNA MTase as well as light-triggered removal from the target DNA.
      This strategy provides a new avenue to reversibly modulate the functionality of
      DNA at MTase target sites.

PMID- 29184955
TI  - (+)- and (-)-Ascomlactone A: a pair of novel dimeric polyketides from a mangrove
      endophytic fungus Ascomycota sp. SK2YWS-L.
AB  - A pair of novel enantiomeric polyketide dimers, (+)- and (-)-ascomlactone A (1a
      and 1b), were obtained from a mangrove endophytic fungus Ascomycota sp. SK2YWS-L.
      The structures were elucidated based on spectroscopic methods, and the absolute
      configurations were determined by X-ray diffraction and electronic circular
      dichroism (ECD) calculations. Ascomlactone A possessed an unprecedented
      polymerization system, which constructed an unusual nine-membered lactone ring
      between the monomers. A possible biogenetic pathway was proposed. Both 1a and 1b
      exhibited significant inhibitory effects against alpha-glucosidase with IC50
      values of 63.7 and 27.9 MUM, respectively. A further docking study provided an
      inside perspective of the action in alpha-glucosidase.

PMID- 29184956
TI  - Influence of imide-substituents on the H-type aggregates of perylene diimides
      bearing cetyloxy side-chains at bay positions.
AB  - A series of perylene-3,4:9,10-tetracarboxylic acid diimides (PDIs, namely TYR
      PDI, AEP-PDI, CET-PDI, ANP-PDI and KOD-PDI), comprising long linear cetyloxy side
      chains functionalized at the 1,7-bay positions and the different substituents
      (i.e., hydrophobic/hydrophilic segments) symmetrically linked at the two imide
      positions of the perylene core were synthesized to investigate the influence of
      imide-substituent patterns on the aggregation behaviours of PDIs. The
      photophysical properties of these PDIs were studied by UV-Vis absorption,
      fluorescence and time-resolved photoluminescence spectroscopy. The differences in
      the photophysical properties of the PDIs indicate (i) blue-shifted and broadening
      absorption properties in both solution and thin-films, (ii) red-shifted and
      broadening fluorescence behavior at their emission maximum in solution, however,
      blue-shifted fluorescence behavior in thin-films, and (iii) obviously longer
      fluorescence life-times corresponding to the existence of rotationally displaced
      H-type aggregates. The formation of short-range ordered rod-like microstructures
      through face-to-face alignment of columnar rectangular H-type PDI aggregates was
      rationalized by scanning electron microscopy. The X-ray diffraction study
      revealed that the formation of well-defined columnar rectangular (Colrp) H-type
      PDI aggregates indicated a nearly constant intracolumnar stacking distance of
      ~3.9 A for all PDIs. All of these findings were consistent with the formation of
      hydrophobic/hydrophilic interactions between the imide-substituents in addition
      to the strong hydrophobic pi-pi stacking interactions between the conjugated
      perylene cores, which were enforced in the H-type PDI aggregates that
      spontaneously self-organized into Colrp structures.

PMID- 29184957
TI  - Liposomal internal viscosity affects the fate of membrane deformation induced by
      hypertonic treatment.
AB  - Artificial lipid membranes have been utilized to understand the physical
      mechanisms of the deformation patterns of live cells. However, typical artificial
      membrane systems contain only dilute components compared to those in the
      cytoplasm of live cells. By using giant unilamellar liposomes containing dense
      protein solutions similar to those in live cells, we here reveal that viscosity
      derived from internal crowding affects the deformation patterns of lipid
      membranes. After hypertonic treatment, liposome deformation patterns transitioned
      from budding to tubing when the initial internal macromolecular concentrations
      were increased. Remarkably, instead of observing different transition
      concentrations between two species of macromolecules, the viscosity at the
      transition concentration was found to be similar. Further analyses clearly
      demonstrated that the internal viscosity affects the deformation patterns of
      lipid membranes induced by hypertonic treatment. These results indicate that the
      viscosity of the cytoplasm is a key factor in determining cell deformation, and
      suggest the association of a process involving dynamic instability, such as a
      viscous fingering phenomenon, during the determination of deformation patterns by
      hypertonic treatment.

PMID- 29184958
TI  - Hydration peculiarities of graphene oxides with multiple oxidation degrees.
AB  - Hydration properties of graphene oxide (GO) are essential for most of its
      potential applications. In this work, we employ atomistic molecular dynamics
      simulations to investigate seven GO compositions with different levels of
      oxygenation. Two atomic charge models for GO are compared: (1, a simplified
      model) sp2 carbons are purely Lennard-Jones sites; (2, a CHELPG model) sp2 carbon
      charges are consistent with the CHELPG scheme. Structural properties were found
      to depend insignificantly on the charge model, whereas thermodynamics appeared
      very sensitive. In particular, the simplified model provides systematically
      stronger GO/water coupling, as compared to the more accurate model. For all GO
      compositions, hydration free energies are in the range of -5 to -45 kJ mol-1
      indicating that hydration is thermodynamically favourable even for modest
      oxidation degrees, thus differing drastically from the cases of pristine graphene
      and graphite. In general, it has been observed that as R increases the high
      oxidation degree obstructs the formation of new hydrogen bonds, which
      considerably affects their hydration properties. Although both the used charge
      models are qualitatively equivalent, the energy and number of hydrogen bonds have
      been shown to be sensitive to the charge set employed. In particular, the
      comparison shows that the simplified model tends to overestimate the GO/water
      interaction energy. The results and discussion presented herein provide a
      physical background for modern applications of GO, e.g. in electrodes of
      supercapacitors and inhibitors in processes involving biological molecules.

PMID- 29184959
TI  - A multi-throughput multi-organ-on-a-chip system on a plate formatted pneumatic
      pressure-driven medium circulation platform.
AB  - This paper reports a multi-throughput multi-organ-on-a-chip system formed on a
      pneumatic pressure-driven medium circulation platform with a microplate-sized
      format as a novel type of microphysiological system. The pneumatic pressure
      driven platform enabled parallelized multi-organ experiments (i.e. simultaneous
      operation of multiple multi-organ culture units) and pipette-friendly liquid
      handling for various conventional cell culture experiments, including cell
      seeding, medium change, live/dead staining, cell growth analysis, gene expression
      analysis of collected cells, and liquid chromatography-mass spectrometry analysis
      of chemical compounds in the culture medium. An eight-throughput two-organ system
      and a four-throughput four-organ system were constructed on a common platform,
      with different microfluidic plates. The two-organ system, composed of liver and
      cancer models, was used to demonstrate the effect of an anticancer prodrug,
      capecitabine (CAP), whose metabolite 5-fluorouracil (5-FU) after metabolism by
      HepaRG hepatic cells inhibited the proliferation of HCT-116 cancer cells. The
      four-organ system, composed of intestine, liver, cancer, and connective tissue
      models, was used to demonstrate evaluation of the effects of 5-FU and two
      prodrugs of 5-FU (CAP and tegafur) on multiple organ models, including cancer and
      connective tissue.

PMID- 29184960
TI  - Damage-free and rapid transfer of CVD-grown two-dimensional transition metal
      dichalcogenides by dissolving sacrificial water-soluble layers.
AB  - As one of the most important family members of two-dimensional (2D) materials,
      the growth and damage-free transfer of transition metal dichalcogenides (TMDs)
      play crucial roles in their future applications. Here, we report a damage-free
      and highly efficient approach to transfer single and few-layer 2D TMDs to
      arbitrary substrates by dissolving a sacrificial water-soluble layer, which is
      formed underneath 2D TMD flakes simultaneously during the growth process. It is
      demonstrated, for monolayer MoS2, that no quality degradation is found after the
      transfer by performing transmission electron microscopy, Raman spectroscopy,
      photoluminescence and electrical transport studies. The field effect mobility of
      the post-transfer MoS2 flakes was found to be improved by 2-3 orders compared
      with that of the as-grown ones. This approach was also demonstrated to be
      applicable to other TMDs, other halide salts as precursors, or other growth
      substrates, indicating its universality for other 2D materials. Our work may pave
      the way for material synthesis of future integrated electronic and optoelectronic
      devices based on 2D TMD materials.

PMID- 29184961
TI  - Highly sensitive detection of hesperidin using AuNPs/rGO modified glassy carbon
      electrode.
AB  - The highly sensitive and selective electrochemical sensor of hesperidin based on
      gold nanoparticles (AuNPs) and reduced graphene oxide (rGO) modified glassy
      carbon electrode (GCE) is reported. The AuNPs and rGO were uniformly introduced
      on the surface of the GCE via electrodeposition without any reducing agents and
      have been characterized by scanning electron microscopy (SEM), energy dispersive
      X-ray spectrometry (EDX), X-ray photoelectron spectroscopy (XPS), FT-IR, and
      electrochemical methods. The AuNPs/rGO not only promoted the accumulation of
      hesperidin onto the GCE surface for quantitative analysis but also accelerated
      the electron transfer between hesperidin and the electrode substrates. Under the
      optimal conditions, hesperidin was determined quantitatively at the AuNPs/rGO/GCE
      using amperometric i-t curve. The results showed that the current obtained on
      detection of hesperidin exhibited a linear correlation with its concentration in
      the range of 5.0 * 10-8 mol L-1-8.0 * 10-6 mol L-1 with a detection limit of 8.2
      * 10-9 mol L-1 (S/N = 3). In addition, good specificity, repeatability,
      reproducibility, and long-term storage stability were achieved for the modified
      electrode, which could be used for the detection of hesperidin in the traditional
      Chinese medicine, Pericarpium Citri Reticulatae.

PMID- 29184962
TI  - One dimensional building blocks for molecular separation: laminated graphitic
      nanoribbons.
AB  - Herein, a new carbon-based graphitic membrane composed of laminated graphitic
      nanoribbons with a nanometer-scale width and micrometer-scale length, the
      graphitic nanoribbon membrane, is reported. Compared to the existing graphitic
      membranes, such as those composed of graphene oxide and carbon nanotubes, the
      developed membrane exhibits several unique characteristics in pressure-driven
      systems. First, the short diffusion length through its interlayer and the free
      volume of its stacked nanoribbons result in high solvent flux regardless of
      solvent polarity (water: 25-250 L m-2 h-1 bar-1; toluene: ~975 L m-2 h-1 bar-1;
      hexane: ~240 L m-2 h-1 bar-1). The flux value for water is one order of magnitude
      higher, while that for nonpolar organic solvents is two to three orders of
      magnitude greater than the corresponding flux values obtained through
      commercially available nanofiltration membranes. Second, the membrane exhibits
      good separation performance, particularly with organic dye molecules (~100%) and
      trivalent ions (~60%), maintaining high solvent flux during extended filtration.
      Finally, the membrane exhibits high stability in various fluids, e.g., 1 M HCl
      solution, 1 M NaOH solution, toluene, ethanol, and water, as well as under
      hydraulic pressures of up to 50 bar. Electron microscopy observation and
      simulation results suggest that such distinctive features of the membrane are
      related to the entangled thin multilayers of the graphitic nanoribbons, which
      possibly originate from the high aspect ratio and narrow width of the
      nanoribbons.

PMID- 29184963
TI  - Slow or fast viral load decay as a predictor of residual viremia level in HIV
      infected patients undergoing successful first-line cART.
AB  - Persistent residual viremia (RV) has been demonstrated in 70-90% of patients
      under successful cART. We analyzed the RV trend during the first year following
      cART-induced virological suppression (VS; HIVRNA <50 copies/ml) to identify
      predictors of achievement and maintenance of ultra-deep RV suppression (URVS; HIV
      RNA <5 copies/ml) in 60 naive patients. These patients were aligned at the time
      of reaching VS and were longitudinally tested with an ultrasensitive HIV-RNA
      assay. The influence of demographics, primary/chronic infection, pre-therapy HIV
      RNA and CD4, cART regimen and time to reach VS on RV trends was evaluated. During
      the first year following VS, median RV levels steadily decreased. RV dropped
      below 5 copies/ml at least once in each patient, but URVS was maintained in 45%
      of patients. RV rebounded to levels fluctuating around 5-10 copies/ml while in
      the remaining 55% of patients. Predictors of early achievement and maintenance of
      stable URVS were fast (<12 weeks) VS achievement after the start of therapy,
      better pre-treatment viro-immunological conditions (lower viremia and higher CD4
      before cART), and treatment initiation during primary infection. These findings
      emphasize the importance of an early onset of potent antiretroviral regimens. RV
      trends should be further studied in detail in the following years of cART.

PMID- 29184964
TI  - Development of an EliSPOT assay for HSV-1 and clinical validation in lung
      transplant patients.
AB  - Cellular immunity plays a major role in the control of HSV-1
      infection/reactivation with a potential impact on the clinical-therapeutic
      management of immunocompromised patients, such as transplant recipients. Herein,
      we quantitatively evaluated T-cell response directed at HSV-1 by a newly
      developed IFN-gamma EliSPOT assay in 53 patients (including 45 lung transplant
      recipients and eight subjects in waiting list). Overall, 62.2% of transplant
      patients and 62.5% of subjects on the waiting list showed a response to HSV-1
      with no significant difference in the level of virus-specific cellular immunity.
      Response tended to be lower in the first three months posttransplantation with a
      progressive recovery of pretransplantation status by the second year and in the
      presence of HSV-1 DNA positivity in bronchoalveolar lavage. As expected, no
      response was found in seronegative patients. No significant difference in the
      level of response according to IgM and IgG status was found. Further studies are
      required to define the role of HSV-1 specific immune response for the clinical
      therapeutic management of lung transplant patients and in other clinical settings
      and to define cut-off levels discriminating between absence/low and strong
      response to be related to the risk of viral infection/reactivation.

PMID- 29184965
TI  - Is self-reported time spent sedentary and in physical activity differentially
      biased by age, gender, body mass index, and low-back pain?
AB  - Objectives This study aimed to determine the extent to which age, gender, body
      mass index (BMI) and low-back pain (LBP) influence bias in self-reported
      sedentary behavior and moderate-to-vigorous physical activity (MVPA) among blue
      collar workers. Methods For 2-4 consecutive working days, 147 workers wore an
      Actigraph accelerometer on the thigh. Proportional time spent sedentary and in
      MVPA was determined using the Acti4 software. The same variables were also self
      reported in a questionnaire. The difference between self-reported and
      accelerometer-based sedentary time and MVPA was calculated and linearly regressed
      against age, gender, BMI, and self-reported LBP intensity as main effects, as
      well as interaction terms combining each of these factors with objectively
      measured exposure. Results Workers objectively spent 64% of their time sedentary
      and 9% in MVPA. On average, self-reports underestimated sedentary time by 1.5%
      and overestimated MVPA by 5.5%. Workers with mild/no LBP appeared to have the
      same size of self-report bias in MVPA regardless of how much MVPA they actually
      had, while workers with high LBP overestimated MVPA to an increasing extent with
      increasing exposure [interaction: B=0.29, 95% confidence interval (CI) 0.05
      0.53]. Age was positively associated with self-report bias in sedentary time
      (B=0.31, 95% CI 0.09-0.54) regardless of actual sedentary time. Conclusions LBP
      and age, but not BMI and gender, introduced differential bias in self-reported
      information on sedentary behavior and MVPA among blue-collar workers. This result
      suggests that bias correction in future studies based on self-reports of
      sedentary time and MVPA should account for LBP and age.

PMID- 29184966
TI  - Recommendations to improve the EU non-technical summaries of animal experiments.
AB  - Under the new Directive 2010/63/EC, member states have to publish non-technical
      summaries (NTS) of the projects involving animals that they authorise. These
      summaries must include information on the objectives of the project including the
      predicted harm and benefits and the number and types of animals to be used.
      Summaries should also demonstrate compliance with the 3Rs. The intention was that
      NTS would help increase the transparency of animal research in the EU. In this
      article, we review the status of the publication of NTS across member states and
      give some general observations on publication speed, identification,
      accessibility and quality. We also review in more detail the quality of reporting
      in a selection of NTS from Germany and the UK. We consistently found that NTS
      from Germany and the UK were deficient in their description of what is being done
      to the animals and what they might experience as a result. Using examples taken
      from specific NTS we highlight what we view to be good and bad examples to assist
      member states and researchers in producing better NTS in the future. The NTS can
      also be an important tool in sharing of best practice in the 3Rs and the
      avoidance of duplicative animal testing. For this to happen however, member
      states need to publish timely, ensure that NTS are accurate and, ideally, there
      needs to be some centralisation of the NTS.

PMID- 29184967
TI  - Towards a national child and adolescent health strategy in Switzerland:
      strengthening surveillance to improve prevention and care.

PMID- 29184968
TI  - Hippocratic method for reduction of chronic locked anterior shoulder
      dislocations.
AB  - PURPOSE: Old shoulder dislocations are usually treated by a variety of surgical
      approaches. Closed reduction of chronic unreduced dislocation is less widely
      reported. This study was to evaluate the outcome of reduction of old anterior
      shoulder dislocations using the Hippocratic method. METHODS: Between January 2008
      and July 2016, patients with unilateral old shoulder dislocations included 10
      women and three men with an average age of 60.00 +/- 2.83 years. Eight
      dislocations involved the right shoulder and five the left shoulder. The average
      delay between dislocation and treatment was 4.46 +/- 0.97 weeks (ranging from 3
      weeks to 6 weeks). One case also had a greater tuberosity fracture. No patients
      had distal nerve or artery dysfunction. The patients were all healthy prior to
      dislocation, i.e., no diabetes, hypertension, or heart disease, etc. Dislocations
      were diagnosed according to anteroposterior shoulder X-rays. Shoulder function
      was assessed using the Constant-Murley score. All manual reductions were
      conducted under general anesthesia using the Hippocratic method. RESULTS: All
      shoulder dislocations were successfully reduced with the Hippocratic method. The
      mean time of closed reduction was 31.46 +/- 7.60 min and the mean hospitalization
      time was 2.77 +/- 1.09 days. No neurovascular injury or humerus fractures were
      noted during hospitalization. The Constant-Murley scores before reduction and
      after reduction were 34.31 +/- 7.25 and 60.92 +/- 8.95, respectively. These
      scores were significantly higher after reduction compared with before reduction
      (P < 0.01). No recurrent dislocation was observed in any patients during the
      follow-up period. CONCLUSION: The closed reduction of old anterior shoulder
      dislocations using the Hippocratic method is not unfeasible and should be
      attempted in selected patients.

PMID- 29184969
TI  - Out-of-pocket health expenditures in patients with bipolar disorder, anxiety,
      schizophrenia and other psychotic disorders: findings from a study in a
      psychiatry outpatient clinic in Turkey.
AB  - PURPOSE: The aim of this study is to explore the amount of OOP health
      expenditures and their determinants in patients with bipolar disorder, anxiety,
      schizophrenia and other psychotic disorders in a psychiatry outpatient clinic of
      Turkey. METHODS: The study group was 191 patients who attended to the Psychiatry
      Outpatient Clinic in June 2014. All patients were previously diagnosed with
      either 'bipolar disorder', 'anxiety disorder' or 'schizophrenia and other
      psychotic disorders'. The dependent variable was OOP expenditures for
      prescription, medical tests and examinations. Independent variables were age,
      gender, education, occupation, existence of social and/or private health
      insurance, equivalent household income and the financial resources. Student's t
      test, Mann-Whitney U test, ANOVA and logistic regression methods were applied
      with SPSS 15.0 for analysis. RESULTS: OOP expenditures per admission were higher
      in patients with schizophrenia and other psychotic disorders ($8.4) than those
      with anxiety disorders ($4.8) (p = 0.02). OOP expenditures were higher in
      patients paying with debit ($9.8) than paying with monthly income ($6.2) (p =
      0.04). OOP expenditures were higher in patients without social health insurance
      ($45.8) than others ($4.8) (p = 0.003). There was not a difference in OOP
      expenditures with respect to equivalent household income level, occupational
      class or education level of the patients (respectively p: 0.90, p: 0.09, p:
      0.52). CONCLUSIONS: Patients who were diagnosed with 'schizophrenia and other
      psychotic disorders' were disadvantaged in paying significantly higher amounts
      for their treatment. A substantial group of these patients compulsorily payed
      with debit. Considering this financial burden, diagnosis of the patient should be
      prioritized in health insurance coverage.

PMID- 29184970
TI  - Neural respiratory reflex induced transversus abdominis muscle action.

PMID- 29184972
TI  - Chromosomal organization of transcription: in a nutshell.
AB  - Early studies of transcriptional regulation focused on individual gene promoters
      defined specific transcription factors as central agents of genetic control.
      However, recent genome-wide data propelled a different view by linking spatially
      organized gene expression patterns to chromosomal dynamics. Therefore, the major
      problem in contemporary molecular genetics concerned with transcriptional gene
      regulation is to establish a unifying model that reconciles these two views. This
      problem, situated at the interface of polymer physics and network theory,
      requires development of an integrative methodology. In this review, we discuss
      recent achievements in classical model organism E. coli and provide some novel
      insights gained from studies of a bacterial plant pathogen, D. dadantii. We
      consider DNA topology and the basal transcription machinery as key actors of
      regulation, in which activation of functionally relevant genes is coupled to and
      coordinated with the establishment of extended chromosomal domains of coherent
      transcription. We argue that the spatial organization of genome plays a
      fundamental role in its own regulation.

PMID- 29184973
TI  - Variability of T1-weighted signal intensity of pericallosal lipomas in the fetus.
AB  - BACKGROUND: Pericallosal lipomas are often associated with corpus callosum
      dysgenesis. The diagnosis of lipoma, suggested on ultrasonography, relies on the
      classic T1 hyperintensity on magnetic resonance imaging (MRI). However, this
      feature may be absent prenatally. OBJECTIVE: Our objective was to study the
      changes of T1 intensity in fetal lipomas with comparison to postnatal/postmortem
      data and to assess the factors influencing the signal variations of pericallosal
      lipomas on prenatal MRI. MATERIALS AND METHODS: Patients with callosum dysgenesis
      and interhemispheric hyperechogenicity suggestive of a pericallosal lipoma with
      available postnatal or postmortem data were included. Gestational age, lipoma
      size and pattern, corpus callosum size and changes in fetal fat T1 intensity were
      recorded. Comparison with postmortem neuropathology was available for one fetus.
      RESULTS: Eleven patients with callosum dysgenesis and pericallosal lipomas (seven
      curvilinear and four tubulonodular) were included. All MRI scans were performed
      in the third trimester. Curvilinear lipomas were thinner and six cases were
      associated with prenatal T1 iso-intensity. Typical T1 hyperintensity appeared on
      postnatal MRI only. All tubulonodular lipomas were much larger and showed
      prenatal T1 hyperintensity. In two patients, the lipoma increased in size on
      postnatal MRI. CONCLUSION: The type and size of a lipoma influence T1 prenatal
      intensity. Absence of T1 intensity was observed in curvilinear lipomas only.
      Curvilinear lipomas are much thinner. Changes in T1 intensity may also be related
      to fat maturation within the lipoma and, subsequently, to gestational age. In the
      case of callosum dysgenesis, absence of prenatal T1 pericallosal hyperintensity
      should not exclude the diagnosis of pericallosal lipoma.

PMID- 29184971
TI  - Positioning of proteasome inhibitors in therapy of solid malignancies.
AB  - Targeting of the protein degradation pathway, in particular, the ubiquitin
      proteasome system, has emerged as an attractive novel cancer chemotherapeutic
      modality. Although proteasome inhibitors have been most successfully applied in
      the treatment of hematological malignancies, they also received continuing
      interest for the treatment of solid tumors. In this review, we summarize the
      current positioning of proteasome inhibitors in the treatment of common solid
      malignancies (e.g., lung, colon, pancreas, breast, and head and neck cancer),
      addressing topics of their mechanism(s) of action, predictive factors and
      molecular mechanisms of resistance.

PMID- 29184974
TI  - Virus-induced apoptosis and phosphorylation form of metacaspase in the marine
      coccolithophorid Emiliania huxleyi.
AB  - Lytic viral infection and programmed cell death (PCD) are thought to represent
      two distinct death mechanisms in phytoplankton, unicellular photoautotrophs that
      drift with ocean currents. PCD (apoptosis) is mainly brought about by the
      activation of caspases, a protease family with unique substrate selectivity.
      Here, we demonstrated that virus infection induced apoptosis of marine
      coccolithophorid Emiliania huxleyi BOF92 involving activation of metacaspase. E.
      huxleyi cells exhibited cell death process akin to that of apoptosis when exposed
      to virus infection. We observed typical hallmarks of apoptosis including cell
      shrinkage, associated nuclear morphological changes and DNA fragmentation.
      Immunoblotting revealed that antibody against human active-caspase-3 shared
      epitopes with a protein of ~ 23 kDa; whose pattern of expression correlated with
      the onset of cell death. Moreover, analysis on two-dimensional gel
      electrophoresis revealed that two spots of active caspase-3 co-migrated with the
      different isoelectric points. Phosphatase treatment of cytosolic extracts
      containing active caspases-3 showed a mobility shift, suggesting that
      phosphorylated form of this enzyme might be present in the extracts.
      Computational prediction of phosphorylation sites based on the amino acid
      sequence of E. huxleyi metacaspase showed multiple phosphorylated sites for
      serine, threonine and tyrosine residues. This is the first report showing that
      phosphorylation modification of metacaspase in E. huxleyi might be required for
      certain biochemical and morphological changes during virus induced apoptosis.

PMID- 29184975
TI  - Gracilibacillus eburneus sp.nov., a moderately halophilic bacterium isolated from
      Xinjiang province, China.
AB  - A novel Gram-staining positive, moderately halophilic, endospore-forming, motile,
      rod-shaped and strictly aerobic strain, designated YIM 93565T, was isolated from
      a salt lake in Xinjiang province of China and subjected to a polyphasic taxonomic
      study. Strain YIM 93565T grew in the range of pH 6.0-9.0 (optimum pH 7.0), 10-45 
      degrees C (optimum 35-40  degrees C) and at salinities of 2-24% (w/v) NaCl
      (optimum 7-10%). Phylogenetic analysis based on 16S rRNA gene sequences indicated
      that strain YIM 93565T clustered with members of the genera Gracilibacillus and
      form a clade with Gracilibacillus bigeumensis KCTC 13130T (95.6% similarity) and
      Gracilibacillus halophilus DSM 17856T (94.9%), which was well separated from
      others. The DNA G + C content of this novel strain was 36.8 mol%. The major fatty
      acids were anteiso-C15:0, iso-C15:0, C16:0 and anteiso-C17:0 and its polar lipids
      consisted of diphosphatidylglycerol, phosphatidylglycerol, one unidentified
      glycolipid and two unidentified phospholipids. The predominant menaquinone was MK
      7. The cell-wall peptidoglycan was based on meso-diaminopimelic acid. Based on
      the results of phylogenetic, physiological and chemotaxonomic comparative
      analyses, the isolate is assigned to a novel species of the genus
      Gracilibacillus, for which the name Gracilibacillus eburneus sp. nov. is
      proposed, with the type strain YIM 93565T (= DSM 23710T = CCTCC AB 2013249T).

PMID- 29184976
TI  - Distinctive Soil Archaeal Communities in Different Variants of Tropical
      Equatorial Forest.
AB  - Little is known of how soil archaeal community composition and diversity differ
      between local variants of tropical rainforests. We hypothesized that (1) as with
      plants, animals, fungi, and bacteria, the soil archaeal community would differ
      between different variants of tropical forest; (2) that spatially rarer forest
      variants would have a less diverse archaeal community than common ones; (3) that
      a history of forest disturbance would decrease archaeal alpha- and beta
      diversity; and (4) that archaeal distributions within the forest would be
      governed more by deterministic than stochastic factors. We sampled soil across
      several different forest types within Brunei, Northwest Borneo. Soil DNA was
      extracted, and the 16S rRNA gene of archaea was sequenced using Illumina MiSeq.
      We found that (1) as hypothesized, there are distinct archaeal communities for
      each forest type, and community composition significantly correlates with soil
      parameters including pH, organic matter, and available phosphorous. (2) As
      hypothesized, the "rare" white sand forest variants kerangas and inland heath had
      lower archaeal diversity. A nestedness analysis showed that archaeal community in
      inland heath and kerangas was mainly a less diverse subset of that in dipterocarp
      forests. However, primary dipterocarp forest had the lowest beta-diversity among
      the other tropical forest types. (3) Also, as predicted, forest disturbance
      resulted in lower archaeal alpha-diversity-but increased beta-diversity in
      contrast with our predictions. (4) Contrary to our predictions, the BetaNTI of
      the various primary forest types indicated community assembly was mainly
      stochastic. The possible effects of these habitat and disturbance-related effects
      on N cycling should be investigated.

PMID- 29184977
TI  - Commentary on: "Comparison of the Effect of Dexamethasone and Tranexamic Acid,
      Separately or in Combination on Post-rhinoplasty and Edema and Ecchymosis".

PMID- 29184978
TI  - Chronic infection and infected non-union of the long bones in paediatric
      patients: preliminary results of bone versus beta-tricalcium phosphate grafting
      after induced membrane formation.
AB  - PURPOSE: Chronic infection (CO) and infected non-union of the long bones are
      relatively rare conditions in paediatric patients. Large bone defects secondary
      to these conditions can be managed with the induced membrane technique. The
      technique requires grafting of the bone void, although it is not yet established
      what bone substitute is the best option. The aim of this work was to evaluate the
      outcome and efficacy of treatment in children with CO and infected non-union of
      the long bones using the induced membrane technique and bone (BG) versus beta
      tricalcium phosphate (BTP) grafting. METHODS: Eight skeletally immature patients
      with CO and infected non-union of the long bones were treated surgically between
      2010 and 2017 by a combination of resection of necrotic infected bone,
      debridement of surrounding soft tissue, osteosynthesis using a stable internal
      fixation when needed, and application of antibiotic-laden cement (ALC) spacer
      inducing new membrane before final bone reconstruction with bone substitutes: BTP
      in five cases, BG (allograft and/or autologous graft) in three cases. A second
      surgical step, once inflammatory markers had normalized, consisted of ALC spacer
      removal, application of BG or BTP graft and concomitant stable osteosynthesis, if
      needed, if this had not been done during the first surgical stage. All the
      patients underwent clinical, laboratory and imaging evaluation before and after
      surgery. Antibiotics were adjusted according to culture and sensitivity. RESULTS:
      Mean patient age at time of diagnosis was 13 +/- four years (range, 4-16) and all
      had at least a 12-month follow-up (range 12-60). Estimated time for induced
      membrane formation was significantly shorter in patients treated with BTP
      compared with BG: 3+/-1 vs. 10+/-2 (p = 0.02). This result was confirmed by
      multivariate analysis (p = 0.044) taking into account adjustment for age of
      patients and time after initial surgery. Time of final union was about 5.5 +/-
      4.1 months (range 2-66). At the last follow-up visit, bone had healed and all the
      patients had resumed daily living and sports activities. CONCLUSION: The induced
      membrane technique with BG or BTP graft can achieve bone healing in large bone
      defects secondary to CO and infected non-union in children and adolescents. The
      choice of bone substitute is important. Our preliminary results show graft
      integration and bone healing can be expected sooner if BTP is used as bone void
      filler.

PMID- 29184979
TI  - Right Ventricular Longitudinal Shortening Before and After Stage I Surgical
      Palliation Correlates with Outcomes.
AB  - Quantification of right ventricular function is difficult, but important, in
      patients with single ventricles. Tissue motion annular displacement (TMAD) is an
      echocardiographic tool that measures displacement of the tricuspid valve relative
      to the apex. We evaluated TMAD, lateral annular displacement (LAD), and
      fractional area change (FAC) for correlation with outcomes. We measured TMAD,
      LAD, FAC, and other variables that may affect prognosis in patients with single
      right ventricle physiology pre- and post-Stage I palliation and correlated them
      with outcomes up to the Glenn procedure. Intra- and inter-observer variability
      for TMAD measurements were 2.7% (1.2-3.5%) and 6.1% (3.3-8.1%), respectively.
      Sixty-six subjects met the inclusion criteria. Pre-Stage I TMAD was 13.7% (SD
      3.9%). TMAD had a linear relationship with FAC (r2 = 0.76). There was a
      correlation between TMAD and hospital stay (p = 0.044) and ECMO/arrest (p =
      0.024). LAD correlated with ECMO/arrest (p = 0.045) and mortality/transplant (p =
      0.049). FAC correlated with in-hospital mortality (p = 0.028). Post-Stage I TMAD
      was 11.8% (SD 3.7%). TMAD, LAD, and FAC all correlated with in-hospital mortality
      and mortality/transplant. In multivariate models, TMAD was independently
      predictive of weight for age Z score pre-Glenn. TMAD, FAC, and LAD correlate with
      clinically significant outcomes after the first-stage palliation. TMAD correlated
      with more outcomes than FAC and was the only measure that was independently
      predictive of any outcome. TMAD is a reproducible measure of RV function in this
      population. TMAD has prognostic value before and after first-stage palliation and
      may outperform more traditional measures.

PMID- 29184980
TI  - Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses
      in head and neck squamous cell carcinoma.
AB  - The NLRP3 inflammasome is a critical innate immune pathway responsible for
      producing active interleukin (IL)-1beta, which is associated with tumor
      development and immunity. However, the mechanisms regulating the inflammatory
      microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show
      that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that
      the IL-1beta concentration was increased in the peripheral blood of HNSCC
      patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor
      tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1beta levels were
      detected in the peripheral blood serum, spleen, draining lymph nodes and tumor
      tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced
      IL-1beta production in an HNSCC mouse model and reduced the numbers of myeloid
      derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated
      macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased
      the numbers of CD4+ and CD8+ T cells in HNSCC mice. Notably, the numbers of
      exhausted PD-1+ and Tim3+ T cells were significantly reduced. A human HNSCC
      tissue microarray showed that NLRP3 inflammasome expression was correlated with
      the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and
      CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results
      demonstrate that the NLRP3 inflammasome/IL-1beta pathway promotes tumorigenesis
      in HNSCC and inactivation of this pathway delays tumor growth, accompanied by
      decreased immunosuppressive cell accumulation and an increased number of effector
      T cells. Thus, inhibition of the tumor microenvironment through the NLRP3
      inflammasome/IL-1beta pathway may provide a novel approach for HNSCC therapy.

PMID- 29184981
TI  - The TET enzymes.
AB  - During the past decade, we have learnt that the most common DNA modification, 5
      methylcytosine (5mC), playing crucial roles in development and disease, is not
      stable but can be actively reversed to its unmodified form via enzymatic
      catalysis involving the TET enzymes. These ground-breaking discoveries have been
      achieved thanks to technological advances in the detection of the oxidized forms
      of 5mC and to the boldness of individual scientists. The TET enzymes require
      molecular oxygen for their catalysis, making them important targets for hypoxia
      research. They also require special cofactors which enable additional levels of
      regulation. Moreover, mutations and other genetic alterations in TETs are found,
      especially in myeloid malignances. This review focuses on the kinetic and
      inhibitory properties of the TET enzymes and the role of TETs in cellular
      differentiation and transformation and in cancer.

PMID- 29184983
TI  - [Compression devices for decongestion therapy : A cross-sectional observational
      survey of handling, pressure, and comfort].
AB  - BACKGROUND: If compression bandaging is not performed in a professional manner,
      the objectives of the therapy may not be achieved and side effects or
      complications may result. OBJECTIVES: This cross-sectional observational survey
      examines the handling of the treatment options: short-stretch bandages with
      padding, multicomponent compression systems, and adaptive compression bandages.
      PARTICIPANTS AND METHODS: During several training sessions on the topic of
      compression therapy, 137 participants performed compression bandagings on each
      other. In this regard, they were asked to achieve a predetermined pressure range
      (short-stretch bandages: 50-60 mm Hg, multicomponent compression systems: 40-50
      mm Hg, adaptive compression bandage: 35-45 mm Hg). To evaluate the efficiency,
      the time used for application, the achieved pressure value, and the comfort were
      determined. RESULTS: Of the 302 bandagings (n = 137 participants), 28.4% lay
      within the given target pressure value range. This included 11.2% of performed
      short-stretch bandages, 35.2% of multicomponent compression systems, and 85.0% of
      adaptive compression bandages. Significant differences in the mean deviations are
      found between the treatment options. The bandage was described as being
      comfortable by 37.7% of users of short-stretch bandages with padding, by 65.0% of
      those wearing a multicomponent compression system, and by 94.6% of participants
      with an adaptive compression bandage. CONCLUSIONS: In practice, short-stretch
      bandages are still the most frequently used care option for the creation of a
      phlebological compression bandage. In this survey, they proved to be unsafe, time
      consuming, and uncomfortable in relation to other treatment options.
      Multicomponent compression systems and adaptive compression bandages are
      treatment options that may be a contemporary alternative which also bares more
      comfort for the patient.

PMID- 29184984
TI  - [Charcot foot masked by erysipelas and peripheral arterial disease].
AB  - Charcot foot is also known as Charcot disease or Charcot arthropathy. The
      associated aseptic destruction of the bones and joints of the foot results due to
      peripheral neuropathy accompanied by impaired pain perception, impaired
      vasomotricity with increased vasodilation, and an unequal weight distribution.
      Because it is frequently diagnosed late and, thus, incorrectly treated, serious
      complications often result. An 86-year-old man in poor health was diagnosed with
      erysipelas of the right foot. The foot was glossy and edematously swollen,
      showing necrosis of the distal phalanx of the third toe. The patient experienced
      pain after a walking distance of approximately 20 m. In addition to erysipelas,
      confirmed neuropathic arthropathy and radiological indicators for Charcot foot
      established peripheral artery disease (PAD) as a third diagnosis. Despite
      multiple systemic antibiotic therapies, there was a progressive disease pattern
      marked by increasing inflammation parameters with an increasing decline of the
      patient's overall health. The patient suffered severe deterioration in spite of
      vascular surgical measures, ultimately leading to his death. In the present case,
      the indicators and respective confirmation of the three overlapping diagnoses
      erysipelas, Charcot foot and PAD are elaborated.

PMID- 29184982
TI  - D2A sequence of the urokinase receptor induces cell growth through alphavbeta3
      integrin and EGFR.
AB  - The urokinase receptor (uPAR) stimulates cell proliferation by forming a
      macromolecular complex with alphavbeta3 integrin and the epidermal growth factor
      receptor (EGFR, ErbB1 or HER1) that we name the uPAR proliferasome. uPAR
      transactivates EGFR, which in turn mediates uPAR-initiated mitogenic signal to
      the cell. EGFR activation and EGFR-dependent cell growth are blocked in the
      absence of uPAR expression or when uPAR activity is inhibited by antibodies
      against either uPAR or EGFR. The mitogenic sequence of uPAR corresponds to the
      D2A motif present in domain 2. NMR analysis revealed that D2A synthetic peptide
      has a particular three-dimensional structure, which is atypical for short
      peptides. D2A peptide is as effective as EGF in promoting EGFR phosphorylation
      and cell proliferation that were inhibited by AG1478, a specific inhibitor of the
      tyrosine kinase activity of EGFR. Both D2A and EGF failed to induce proliferation
      of NR6-EGFR-K721A cells expressing a kinase-defective mutant of EGFR. Moreover,
      D2A peptide and EGF phosphorylate ERK demonstrating the involvement of the MAP
      kinase signalling pathway. Altogether, this study reveals the importance of
      sequence D2A of uPAR, and the interdependence of uPAR and EGFR.

PMID- 29184985
TI  - [Quality of self-applied compression bandages in patients with chronic venous
      ulcers : Results of a prospective clinical study].
AB  - BACKGROUND: For effective compression therapy in patients with venous leg ulcers,
      sufficient pressure is essential. In everyday life, it is often the patients
      themselves who apply the compression bandages. Many of these patients have
      restriction in their movement and had been rarely trained adequately. Hence,
      there was the question of how efficient are the autonomously applied compression
      bandages of those patients. PATIENTS AND METHODS: In all, 100 consecutive
      patients with venous leg ulcer were asked to apply compression bandages on their
      own leg. We documented both the achieved compression and formal criteria of
      correct performance. RESULTS: A total of 59 women and 41 men with an average age
      of 70.3 years were included in the study. Overall 43 patients were not able to
      apply a compression bandage because of physical limitations. The measured
      pressure values in the remaining 57 patients ranged between 6 and 93 mm Hg (mean
      28.3 mm Hg). Eleven patients reached the prescribed effective compression
      pressure. Of these, formal errors were found in 6 patients, so that only 5
      patients had correctly applied the compression bandages. CONCLUSION: Our data
      show that most patients with venous leg ulcers are not able to apply effective
      compression therapy with short-stretch bandages to themselves. Multilayer
      systems, adaptive compression bandages, and ulcer stocking systems today are
      possibly easier and more effective therapy options. Alternatively short-stretch
      bandages could be applied by trained persons but only under the control with
      pressure measuring probes.

PMID- 29184986
TI  - ?

PMID- 29184987
TI  - Ventilation during extracorporeal support : Why and how.
AB  - The main target of extracorporeal support is to achieve viable gas exchange,
      while minimizing the risk of ventilator-induced lung injury, achieved through a
      decreased mechanical ventilation load on the natural lung. However, during veno
      venous extracorporeal membrane oxygenation (ECMO), mechanical ventilation is
      still necessary in order to prevent lung collapse and/or if extracorporeal blood
      flow is not sufficient to guarantee adequate gas exchange. In this review, we
      will summarize the physiology of extracorporeal support and the rationale for
      continuing mechanical ventilation in this context. Furthermore, we will review
      the current clinical practice among ECMO centers and their suggestions regarding
      mechanical ventilator settings. While optimal ventilatory settings are still a
      matter of debate, the use of a strategy combining low tidal volume and limited
      inspiratory pressures is accepted worldwide. On the contrary, the choice of
      applied positive end-expiratory pressure (PEEP) varies between the total rest
      strategy and open lung strategy. Finally, the use of assisted or spontaneous
      ventilation will be discussed.

PMID- 29184988
TI  - Expression and characterization of a recombinant porcinized antibody against the
      E2 protein of classical swine fever virus.
AB  - Classical swine fever virus (CSFV) is the causative agent of classical swine
      fever (CSF), a highly contagious and economically important disease of pigs. The
      envelope glycoprotein E2 of CSFV is the major antigen that induces neutralizing
      antibodies and confers protection against CSFV infections. Previously, we
      developed a murine monoclonal antibody (MAb), HQ06, against the E2 protein of
      CSFV. To produce the antibody conveniently and stably, the genes coding for the
      variable regions of the heavy and light chains of HQ06 and constant region genes
      from the swine antibody were fused and cloned into lentiviral expression vectors
      to express a recombinant porcinized MAb (rHQ06Sw) in mammalian cells. rHQ06Sw was
      able to react with the E2 protein or the CSFV virions specifically in different
      assays. Notably, rHQ06Sw could neutralize CSFV infection in a dose-dependent
      manner. Taken together, the functional porcinized MAb rHQ06Sw was generated,
      which can be used to develop novel diagnostic assays or to investigate the
      structure and functions of the E2 protein.

PMID- 29184989
TI  - Enhanced avermectin production by Streptomyces avermitilis ATCC 31267 using high
      throughput screening aided by fluorescence-activated cell sorting.
AB  - Avermectins, produced by Streptomyces avermitilis, are important antiparasitic
      agents. The use of traditional microbial breeding methods for this organism has
      been limited by the low-throughput shake flask-based screening process. The
      unique growth cycle of actinomycetes makes the establishment of a reliable high
      throughput screening (HTS) process difficult. To enhance the efficiency of
      screening strains with high yields of avermectin, a HTS process aided by
      fluorescence-activated cell sorting (FACS) was established. Four different spore
      solutions were investigated for maintaining a relatively high viability of
      spores. Propidium iodide (PI) and fluorescein diacetate (FDA) were used to
      discriminate between dead and live spores using the FACS system. Spores stained
      with 7-MUg/mL PI and 15-MUg/mL FDA at 4  degrees C in the dark for 30 min
      resulted in optimum sorting. Spores were treated by atmospheric and room
      temperature plasma (ARTP). Single live spores were sorted and sprayed into 96
      well microtiter plates containing 50 MUL of solid agar culture medium. Solid
      liquid combinatorial microculture was used for high-throughput avermectin
      culture. A high-titer avermectin producer (G9) was obtained from 5760 mutants
      after mutagenesis and HTS. Compared with the original strain, the titer was
      improved by 18.9% on flask culture and 20.6% on fermenter, respectively. The HTS
      process established in this study could easily be transferred to other similar
      target products produced by actinomycetes.

PMID- 29184990
TI  - Microbial biosensors for analytical applications.

PMID- 29184991
TI  - Universal fluorometric aptasensor platform based on water-soluble conjugated
      polymers/graphene oxide.
AB  - We designed a universal and sensitive fluorometric aptasensor that uses a
      fluorescence resonance energy transfer (FRET) mechanism. In the aptasensor, water
      soluble conjugated poly(9,9-bis(6'-N,N,N-trimethylammonium)hexyl)fluorine
      phenylene (PFP) is used as the energy donor and a carboxyfluorescein (FAM)
      labeled aptamer is used as the energy acceptor. Graphene oxide (GO) used as a
      quencher can specifically adsorb the aptamer, leading to quenching of the FAM
      fluorescence. In the presence of targets, the aptamer can change its conformation
      to prevent adsorption by GO. Strong FRET was thus obtained owing to the
      electrostatic interactions between PFP and the aptamer. In contrast, in the
      absence of targets, the FRET was weak because of GO specifically adsorbing the
      aptamer and quenching the fluorescence. Bisphenol A (a pollutant molecule) and
      dopamine (a biomolecule) were used as models to successfully validate the
      feasibility, universality, and high selectivity and sensitivity of this
      aptasensor. This method can detect BPA at environmentally relevant concentrations
      (less than 1 ng/mL) with a limit of detection of 0.005 ng/mL. A low limit of
      detection (1.0 nmol/L) was also obtained for dopamine. In addition, this
      aptasensor is applicable in real samples and in diluted human plasma and human
      serum. Good recovery rates from 95% to 105% and from 95% to 107% were obtained
      for bisphenol A and dopamine, respectively. Furthermore, adenosine detection was
      successfully achieved by the same mechanism, proving the universality. It is
      expected that the aptasensor could be applied in detecting other contaminants,
      biomolecules, and heavy metal ions by a change in only the aptamer sequence.
      Graphical abstract A universal and sensitive fluorometric aptasensor was
      developed for the detection of small molecules that uses a fluorescence resonance
      energy transfer (FRET) mechanism. GO graphene oxide. PFP poly(9,9-bis(6'-N,N,N
      trimethylammonium)hexyl)fluorine phenylene.

PMID- 29184992
TI  - A fluorescent immunochromatographic strip test using a quantum dot-antibody probe
      for rapid and quantitative detection of 1-aminohydantoin in edible animal
      tissues.
AB  - A rapid, simple, and sensitive fluorescent immunochromatographic strip test
      (ICST) based on quantum dots (QDs) has been developed to detect 1-aminohydantoin
      (AHD), a major metabolite of nitrofurantoin in animal tissues. To achieve this,
      QD-labeled antibody conjugates, which consist of CdSe/ZnS QDs and monoclonal
      antibodies, were prepared by an activated ester method. Under optimal conditions,
      with the nitrophenyl derivative of AHD as the target, the ICST had a linear range
      from 0.1 to 100 ng/mL, with a correlation coefficient of 0.9656 and a 50%
      inhibitory concentration of 4.51 ng/mL. The limit of detection was 0.14 ng/g,
      which was below the minimum required performance limit of 1 MUg/kg for AHD
      established by the European Commission. The recoveries for AHD ranged from 81.5%
      to 108.2%, with coefficients of variation below 13%, based on intraday and
      interday analysis. Furthermore, for AHD in real samples, the ICST showed high
      reliability and high correlation with liquid chromatography-tandem mass
      spectrometry (correlation coefficient of 0.9916). To the best of our knowledge,
      this is the first report of a novel and sensitive method based on a fluorescent
      ICST to detect AHD below the minimum required performance limit. The ICST
      demonstrated high reliability, and could be ideally suited for rapid, simple, and
      on-site screening of AHD contamination in animal tissues. Graphical abstract A
      rapid, simple, and sensitive fluorescent immunochromatographic strip test that is
      based on quantum dots was developed to detect 1-aminohydantoin (AHD), a major
      metabolite of nitrofurantoin in animal tissues. 2-NBA 2-nitrobenzaldehyde, NP
      nitrophenyl.

PMID- 29184993
TI  - Evaluation of oxidized phospholipids analysis by LC-MS/MS.
AB  - Phospholipids (PLs) represent a class of metabolites of interest for evaluating
      the relationship between diet and the development of several metabolic diseases.
      Given that PLs are rich in unsaturated fatty acids, they can be oxidized. Because
      of their structure and reactivity, oxidized phospholipids (PLs-Ox) are
      increasingly recognized as markers of oxidative stress and of various diseases
      associated with inflammation. Therefore, there is a growing interest in studying
      PLs-Ox in lipidomics. Because of their limited commercial availability, very
      little information is currently available in databases to identify these
      molecules. The aim of this study is to acquire new knowledge about PLs-Ox in
      order to propose an analytical strategy for their analyses. For this purpose, a
      synthesis method of PLs-Ox, in auto-oxidation, has been developed and applied on
      phosphatidylcholine and phosphatidylethanolamine molecular species with various
      chain lengths, degree, and position of unsaturations. An analysis method based on
      mass (MS) and tandem mass spectrometry coupled to electrospray ionization was
      then developed and enabled the identification of a great diversity of long- and
      short-chain oxidation products. Formation kinetics of oxidation products was
      evaluated. Results showed that the formation of oxidized compounds was largely
      influenced by the degree of unsaturation on fatty acid chains. Oxidation time
      promotes the formation of some biologically important oxidation products.
      Coupling the MS method with liquid chromatography in flow injection analysis mode
      enabled the development of a full analytical strategy. Structural analysis of PLs
      Ox allowed the enrichment of databases with important information to identify
      these molecules in biological matrices.

PMID- 29184994
TI  - Synthetic biology for microbial heavy metal biosensors.
AB  - Using recombinant DNA technology, various whole-cell biosensors have been
      developed for detection of environmental pollutants, including heavy metal ions.
      Whole-cell biosensors have several advantages: easy and inexpensive cultivation,
      multiple assays, and no requirement of any special techniques for analysis. In
      the era of synthetic biology, cutting-edge DNA sequencing and gene synthesis
      technologies have accelerated the development of cell-based biosensors. Here, we
      summarize current technological advances in whole-cell heavy metal biosensors,
      including the synthetic biological components (bioparts), sensing and reporter
      modules, genetic circuits, and chassis cells. We discuss several opportunities
      for improvement of synthetic cell-based biosensors. First, new functional modules
      must be discovered in genome databases, and this knowledge must be used to
      upgrade specific bioparts through molecular engineering. Second, modules must be
      assembled into functional biosystems in chassis cells. Third, heterogeneity of
      individual cells in the microbial population must be eliminated. In the
      perspectives, the development of whole-cell biosensors is also discussed in the
      aspects of cultivation methods and synthetic cells.

PMID- 29184995
TI  - Quantification of size effect on protein rotational mobility in cells by 19F NMR
      spectroscopy.
AB  - Protein diffusion in living cells might differ significantly from that measured
      in vitro. Little is known about the effect of globular protein size on rotational
      diffusion in cells because each protein has distinct surface properties, which
      result in different interactions with cellular components. To overcome this
      problem, the B1 domain of protein G (GB1) and several concatemers of the protein
      were labeled with 5-fluorotryptophan and studied by 19F NMR in Escherichia coli
      cells, Xenopus laevis oocytes, and in aqueous solutions crowded with glycerol, or
      Ficoll70TM and lysozyme. Relaxation data show that the size dependence of protein
      rotation in cells is due to weak interactions of the target protein with cellular
      components, but the effect of these interactions decreases as protein size
      increases. The results provide valuable information for interpreting protein
      diffusion data acquired in living cells. Graphical abstract Size matters. The
      protein rotational mobility in living cells was assessed by 19F NMR. The size
      dependence effect may arise from weak interactions between protein and
      cytoplasmic components.

PMID- 29184996
TI  - Polymeric ionic liquid-assembled graphene-immobilized silica composite for
      selective isolation of human serum albumin from human whole blood.
AB  - Polymeric ionic liquids (PILs) with 1-vinyl-3-ethylimidazolium cations and two
      different anions of Br- and PF6- were assembled onto the surface of graphene (G)
      nanosheets. The derived two composites, i.e., PIL(Br)-G and PIL(PF6)-G, were
      further efficiently immobilized onto the surface of silica nanoparticles via self
      assembly technique. The obtained two PIL-G/SiO2 nanocomposites exhibited diverse
      adsorption performances toward proteins through adjusting the anions of PILs.
      Electrostatic attractions between proteins and the nanocomposites dominated
      protein adsorption, while the presence of PF6- anions weakened electrostatic
      interactions and deteriorated the selective adsorption of target protein, i.e.,
      bovine serum albumin (BSA) in this case. Specifically, PIL(Br)-G/SiO2
      nanocomposite displayed high selectivity toward BSA and a high adsorption
      efficiency of ca. 98% was achieved for 100 mg L-1 BSA in a Britton-Robinson (B-R)
      buffer at pH 5. HPLC analysis demonstrated the selectivity of PIL(Br)-G/SiO2
      nanocomposite toward BSA in the presence of abundant hemoglobin and cytochrome c.
      The practical applicability was verified by performing selective isolation of
      human serum albumin (HSA) from human whole blood. Graphical abstract Selective
      isolation of human serum albumin from blood by polymeric ionic liquid assembled
      graphene immobilized silica nanocomposite with tunable anions.

PMID- 29184997
TI  - beta-Cyclodextrin molecularly imprinted solid-phase microextraction coatings for
      selective recognition of polychlorophenols in water samples.
AB  - A series of beta-cyclodextrin derivatives were designed and synthesized. The
      derivatives were investigated as functional monomers in molecularly imprinted
      polymeric solid-phase microextraction (MIP-SPME) fiber coatings. The coatings,
      with a layer thickness of 250 MUm, were immobilized onto stainless steel using a
      capillary tube as a mold. This study employed a simple, easy, and reproducible
      method to prepare uniform coatings for polychlorophenols extraction. The
      combination of molecular inclusion effects and the molecular imprinting sites was
      expected to enhance the molecular recognition ability for polychlorophenols.
      Compared with non-imprinted polymer coatings and MIP coatings with methacrylic
      acid as the functional monomer, the beta-cyclodextrin MIP-SPME coatings exhibited
      significantly higher extraction amounts and excellent selectivity to the template
      of triclosan. The MIP-SPME coatings exhibited a favorable synergistic extraction
      capacity resulting from the beta-cyclodextrin cavity and molecularly imprinted
      binding sites. The method of beta-cyclodextrin MIP-SPME coupled with high
      performance liquid chromatography (HPLC) for triclosan and polychlorophenols
      analysis in real water samples was developed. The limit of quantification was 1
      MUg/L for the three polychlorophenols. The recovery for three analytes ranged
      from 83.71% to 109.98%, with the relative standard deviation (RSD) of 2.83% to
      12.19%. The beta-cyclodextrin MIP-SPME fiber coatings could be used for at least
      100 cycles. Graphical Abstract Synergistic effects in beta-cyclodextrin MIP-SPME.

PMID- 29184998
TI  - Fast automated online xylanase activity assay using HPAEC-PAD.
AB  - In contrast to biochemical reactions, which are often carried out under automatic
      control and maintained overnight, the automation of chemical analysis is usually
      neglected. Samples are either analyzed in a rudimentary fashion using in situ
      techniques, or aliquots are withdrawn and stored to facilitate more precise
      offline measurements, which can result in sampling and storage errors. Therefore,
      in this study, we implemented automated reaction control, sampling, and analysis.
      As an example, the activities of xylanases on xylotetraose and soluble xylan were
      examined using high-performance anion exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD). The reaction was performed in HPLC vials
      inside a temperature-controlled DionexTM AS-AP autosampler. It was started
      automatically when the autosampler pipetted substrate and enzyme solution into
      the reaction vial. Afterwards, samples from the reaction vial were injected
      repeatedly for 60 min onto a CarboPacTM PA100 column for analysis. Due to the
      rapidity of the reaction, the analytical method and the gradient elution of 200
      mM sodium hydroxide solution and 100 mM sodium hydroxide with 500 mM sodium
      acetate were adapted to allow for an overall separation time of 13 min and a
      detection limit of 0.35-1.83 mg/L (depending on the xylooligomer). This
      analytical method was applied to measure the soluble short-chain products
      (xylose, xylobiose, xylotriose, xylotetraose, xylopentaose, and longer
      xylooligomers) that arise during enzymatic hydrolysis. Based on that, the
      activities of three endoxylanases (EX) were determined as 294 U/mg for EX from
      Aspergillus niger, 1.69 U/mg for EX from Bacillus stearothermophilus, and 0.36
      U/mg for EX from Bacillus subtilis. Graphical abstract Xylanase activity assay
      automation.

PMID- 29184999
TI  - LC-MS/MS imaging with thermal film-based laser microdissection.
AB  - Mass spectrometry (MS) imaging is a useful tool for direct and simultaneous
      visualization of specific molecules. Liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) is used to evaluate the abundance of molecules in tissues
      using sample homogenates. To date, however, LC-MS/MS has not been utilized as an
      imaging tool because spatial information is lost during sample preparation. Here
      we report a new approach for LC-MS/MS imaging using a thermal film-based laser
      microdissection (LMD) technique. To isolate tissue spots, our LMD system uses a
      808-nm near infrared laser, the diameter of which can be freely changed from 2.7
      to 500 MUm; for imaging purposes in this study, the diameter was fixed at 40 MUm,
      allowing acquisition of LC-MS/MS images at a 40-MUm resolution. The isolated
      spots are arranged on a thermal film at 4.5-mm intervals, corresponding to the
      well spacing on a 384-well plate. Each tissue spot is handled on the film in such
      a manner as to maintain its spatial information, allowing it to be extracted
      separately in its individual well. Using analytical LC-MS/MS in combination with
      the spatial information of each sample, we can reconstruct LC-MS/MS images. With
      this imaging technique, we successfully obtained the distributions of
      pilocarpine, glutamate, gamma-aminobutyric acid, acetylcholine, and choline in a
      cross-section of mouse hippocampus. The protocol we established in this study is
      applicable to revealing the neurochemistry of pilocarpine model of epilepsy. Our
      system has a wide range of uses in fields such as biology, pharmacology,
      pathology, and neuroscience. Graphical abstract Schematic Indication of LMD-LC
      MS/MS imaging.

PMID- 29185003
TI  - Ultrasound measurements of Achilles tendon length using skin markings are more
      reliable than extended-field-of-view imaging.
AB  - PURPOSE: Elongation of the Achilles tendon has been associated with poorer
      function in patients treated for ruptures. This has led to the development of
      various ultrasound-based measurements, and the purpose of the present study was
      to compare the reliability of three ultrasound-based measuring procedures.
      METHODS: Twenty healthy individuals (40 tendons) were assessed by two testers at
      two occasions, 12 weeks apart. The tendon length was measured from the calcaneal
      insertion to the mid-sagittal muscle tendon junction (MTJ) using skin markings or
      extended-field-of-view (EFOV) imaging, or from the calcaneal insertion to the
      distal medial MTJ using skin markings. Test-retest and inter-tester reliability
      as well as side-to-side length differences were assessed for all three
      procedures. RESULTS: Test-retest intraclass correlation coefficients (ICCs) for
      measurements from the mid-sagittal MTJ using EFOV imaging and skin markings, and
      from the distal medial MTJ using skin markings were 0.83, 0.90 and 0.96 for
      tester 1 and 0.87, 0.91 and 0.96 for tester 2, respectively. The corresponding
      inter-tester ICCs were 0.85, 0.91 and 0.96. Side-to-side lengths were
      significantly different for measurements from the mid-sagittal MTJ and the distal
      medial MTJ using skin markings, with mean differences of 0.3 and 0.4 cm,
      respectively. CONCLUSIONS: Test-retest and inter-tester ICCs were excellent for
      all three measuring procedures, however, the use of skin markings provided
      consistently better agreement and reliability compared to EFOV images. The best
      agreement and highest ICCs were achieved for measurements from the distal medial
      MTJ, but side-to-side length differences warrant caution when contralateral
      measurements are used to evaluate tendon elongation. LEVEL OF EVIDENCE: III.

PMID- 29185004
TI  - Poor knee function after ACL reconstruction is associated with attenuated landing
      force and knee flexion moment during running.
AB  - PURPOSE: Poor knee function after anterior cruciate ligament reconstruction
      (ACLR) may increase the risk of future knee symptoms and knee osteoarthritis via
      abnormal knee joint loading patterns, particularly during high-impact activity.
      This study aimed to assess the relationship between poor self-reported or
      clinically measured knee function and knee moments/vertical ground reaction force
      (vGRF) in individuals following ACLR. METHODS: 61 participants (mean 16.5 +/- 3
      months following ACLR, 23 women) completed a patient-reported knee function
      questionnaire and three hop tests (% of uninvolved limb). Participants were
      divided into satisfactory and poor knee function groups (poor < 85% patient
      reported knee function and/or < 85% hop test symmetry). The knee biomechanics of
      both groups were assessed with three-dimensional motion analysis during the
      stance phase of overland running at self-selected speeds, and the association
      between knee function and knee moments was assessed using analysis of covariance
      with running speed as a covariate. RESULTS: Participants with poor knee function
      (n = 30) ran with significantly smaller peak knee flexion moments (moderate
      effect size 0.7, p = 0.03) and significantly smaller peak vGRFs (large effect
      size 1.0, p = 0.002) compared to those with satisfactory knee function (n = 31).
      No significant differences were observed for knee adduction and knee external
      rotation moments or knee kinematics. CONCLUSION: Individuals following ACLR with
      poor self-reported knee function and/or hop test performance demonstrate knee
      moments during running that may be associated with lower knee joint contact
      forces. These findings provide greater understanding of the relationship between
      knee biomechanics during running and clinical assessments of knee function. LEVEL
      OF EVIDENCE: III. Cross-sectional study.

PMID- 29185006
TI  - Endoscopic shelf acetabuloplasty can improve clinical outcomes and achieve return
      to sports-related activity in active patients with hip dysplasia.
AB  - PURPOSE: To investigate clinical outcomes and return to sports-related activity
      following endoscopic shelf acetabuloplasty combined with labral repair in the
      treatment of the active patients with developmental dysplasia of the hip (DDH).
      METHODS: Between 2011 and 2013, 32 patients (36 hips; 11 males and 21 females; 11
      right 17 left 4 bilateral; median age 28.5, range 12-51 years), who underwent
      endoscopic shelf acetabuloplasty combined with labral repair and met the
      inclusion criteria were enrolled in this study. There was a minimum follow-up of
      2 years (average 32.3 +/- 3 months, range 24-48 months). Patient-reported outcome
      (PRO) scores including the modified Harris Hip Score (MHHS) and Non-Arthritis Hip
      Score (NAHS) were obtained preoperatively and at final follow-up for the
      assessment of surgical outcomes. RESULTS: The mean MHHS significantly improved
      from 68.4 +/- 14.3 (range 23.1-95.7) preoperatively to 94.5 +/- 8.5 (range 66
      100) at final follow-up (p = 0.001). Similarly, the NAHS also significantly
      improved from 51.3 +/- 11.9 (range 23-76) preoperatively to 73.0 +/- 7.4 (range
      44-80) at final follow-up (p = 0.001). The mean LCE angle significantly increased
      postoperatively but partially decreased at final follow-up (mean preoperative
      versus postoperative versus final follow-up: 16.0 range 5-24, versus 40.1 range
      27-58, versus 30.1 range 20-41. p = 0.001, respectively). There were 3 patients
      who returned to a higher activity level, 20 patients who returned to the same
      activity level, and 6 patients who returned to a lower activity level. The mean
      period from surgery to return to play was 9.0 +/- 3.5 months (range 5-18).
      CONCLUSION: Endoscopic shelf acetabuloplasty provides promising clinical outcomes
      and return to sports-related activity for active patients with DDH. LEVEL OF
      EVIDENCE: Level IV.

PMID- 29185005
TI  - Larger range of motion and increased return to activity, but higher revision
      rates following unicompartmental versus total knee arthroplasty in patients under
      65: a systematic review.
AB  - PURPOSE: Due to the lack of comparative studies, a systematic review was
      conducted to determine revision rates of unicompartmental and total knee
      arthroplasty (UKA and TKA), and compare functional outcomes, range of motion and
      activity scores in patients less than 65 years of age. METHODS: A literature
      search was performed using PubMed, Embase, and Cochrane systems since 2000. 27
      UKA and 33 TKA studies were identified and included. Annual revision rate (ARR),
      functional outcomes, and return to activity were assessed for both types of
      arthroplasty using independent t tests. RESULTS: Four level I studies, 12 level
      II, 16 level III, and 29 level IV were included, which reported on outcomes in
      2224 UKAs and 4737 TKAs. UKA studies reported 183 revisions, yielding an ARR of
      1.00 and extrapolated 10-year survivorship of 90.0%. TKA studies reported 324 TKA
      revisions, resulting in an ARR of 0.53 and extrapolated 10-year survivorship of
      94.7%. Functional outcomes scores following UKA and TKA were equivalent, however,
      following UKA larger ROM (125 degrees  versus 114 degrees , p = 0.004) and higher
      UCLA scores were observed compared to TKA (6.9 versus 6.0, n.s.). CONCLUSION:
      These results show that good-to-excellent outcomes can be achieved following UKA
      and TKA in patients less than 65 years of age. A higher ARR was noted following
      UKA compared to TKA. However, improved functional outcomes, ROM and return to
      activity were found after UKA than TKA in this young population. Comparative
      studies are needed to confirm these findings and assess factors contributing to
      failure at the younger patient population. Outcomes of UKA and TKA in patients
      younger than 65 years are both satisfying, and therefore, both procedures are not
      contraindicated at younger age. UKA has several important advantages over TKA in
      this young and frequently more active population. LEVEL OF EVIDENCE: IV.

PMID- 29185007
TI  - Awareness and Adoption of Soil and Water Conservation Technologies in a
      Developing Country: A Case of Nabajuzi Watershed in Central Uganda.
AB  - Soil and water conservation technologies have been widely available in most parts
      of Uganda. However, not only has the adoption rate been low but also many farmers
      seem not to be aware of these technologies. This study aims at identifying the
      factors that influence awareness and adoption of soil and water conservation
      technologies in Nabajuzi watershed in central Uganda. A bivariate probit model
      was used to examine farmers' awareness and adoption of soil and water
      conservation technologies in the watershed. We use data collected from the
      interview of 400 households located in the watershed to understand the factors
      affecting the awareness and adoption of these technologies in the study area.
      Findings indicate that the likelihood of being aware and adopting the
      technologies are explained by the age of household head, being a tenant, and
      number of years of access to farmland. To increase awareness and adoption of
      technologies in Uganda, policymakers may expedite the process of land titling as
      farmers may feel secure about landholding and thus adopt these technologies to
      increase profitability and productivity in the long run. Incentive payments to
      farmers residing in the vulnerable region to adopt these considered technologies
      may help to alleviate soil deterioration problems in the affected area.

PMID- 29185008
TI  - Satellite Images Combined with Field Data Reveal Negative Changes in the
      Distribution of Babassu Palms after Clearing off Amazonian Forests.
AB  - When the Amazonian rain forest is cut to create pasture, some of the original
      vegetal species survive clearing, even expressing their ability to invade agro
      systems. It is true of the babassu palm, which can be considered, paradoxically,
      a natural resource by the "Interstate Movement of Babassu Fruit Breaker Women" or
      as native weed by land owners-farmers. To manage potential conflict of land uses,
      we study here the current density of this palm tree in different habitats, based
      on a combination of field data and remote sensing data. Firstly, we checked that
      the field survey methodology (i.e., counting free-trunk palm trees over 20 cm in
      circumference) provides density values compatible with those stemming from
      satellite images interpretation. We can see then that, a PA-Benfica Brazilian
      territory revealed an average density of the babassu lower in pastures (2.86
      ind/ha) than in the dense forest (4.72 ind/ha) from which they originate and than
      in fallow land (4.31 ind/ha). We analyze in detail density data repartition in
      three habitats and we discuss results from the literature on the density of this
      palm tree versus its resilience at different developmental stages after forest
      clearing, depending on anthropogenic-or not-factors, including solar radiation,
      fire, weeding, clear cutting, burying fruit, and competition with forage grass.
      All these results can be exploited for the design of future management plans for
      the babassu palm and we think that the linked methodology and interdisciplinary
      approach can be extended to others palms and trees species in similar problematic
      issues.

PMID- 29185009
TI  - 42nd Annual Meeting - Vancouver, Canada, June 20 - 24, 2017.

PMID- 29185010
TI  - Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in
      patients with metastatic prostate cancer undergoing docetaxel chemotherapy.
AB  - PURPOSE: To investigate the value of 68Ga-HBED-CC PSMA (68Ga-PSMA) PET/CT for
      response assessment in metastatic castration-sensitive and castration-resistant
      prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy. METHODS: 68Ga
      PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of
      upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three
      cycles of palliative docetaxel chemotherapy. Radiographic treatment response was
      evaluated separately on the 68Ga-PSMA PET and CT datasets. Changes in 68Ga-PSMA
      uptake (SUVmean) were assessed on a per-patient and a per-lesion basis using the
      PERCIST scoring system with slight modification. Treatment response was defined
      as absence of any PSMA uptake in all target lesions on posttreatment PET
      (complete response, CR) or a decrease in summed SUVmean of >=30% (partial
      response, PR). The appearance of a new PET-positive lesion or an increase in
      summed SUVmean of >=30% (progressive disease, PD) indicated nonresponse. A
      moderate change in summed SUVmean (between -30% and +30%) without a change in the
      number of target lesions was defined as stable disease (SD). For treatment
      response assessment on CT, RECIST1.1 criteria were used. Radiographic responses
      on 68Ga-PSMA PET [RR(PET)] and on CT [RR(CT)] were compared and correlated with
      biochemical response (BR). A decrease in serum PSA level of >=50% was defined as
      biochemical PR. RESULTS: Biochemical PR was found in six of seven patients with
      mCSPC (86%, 95% confidence interval 42% to 99.6%). The concordance rate was
      higher between BR and RR(PET) than between BR and RR(CT) (6/7 vs. 3/6 patients.
      68Ga-PSMA PET and CT were concordant in only three patients (50%, 12% to 88%). In
      mCRPC patients, biochemical PR was found in six of 16 patients (38%, 15% to 65%).
      Outcome prediction was concordant between BR and RR(PET) in nine of 16 patients
      (56%), and between BR and RR(CT) in only four of 12 patients (33%) with target
      lesions on CT. 68Ga-PSMA PET and CT results corresponded in seven of 12 patients
      (58%, 28% to 85%). CONCLUSION: Our preliminary results suggest that 68Ga-PSMA PET
      might be a promising method for treatment response assessment in mCSPC and mCRPC.
      The data indicate that for different metastatic sites, the performance of 68Ga
      PSMA PET in response assessment might be superior to that of the conventional CT
      approach and could help differentiate between progressive disease and treatment
      response. Because of the limited number of patients, the differences revealed in
      our study were not statistically significant. Thus larger and prospective studies
      are clearly needed and warranted to confirm the value of 68Ga-PSMA PET as an
      imaging biomarker for response assessment.

PMID- 29185011
TI  - Plasma concentrations of 8-hydroxy-2'-deoxyguanosine and risk of kidney disease
      and death in individuals with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Oxidative stress is involved in the pathogenesis of diabetic
      kidney disease. We evaluated the association between 8-hydroxy-2'-deoxyguanosine
      (8-OHdG), a marker of DNA oxidative damage, and end-stage renal disease (ESRD) or
      death in individuals with type 1 diabetes. METHODS: Plasma 8-OHdG concentrations
      were measured at baseline in participants with type 1 diabetes from GENEDIAB (n =
      348) and GENESIS (n = 571) cohorts. A follow-up was conducted in 205 and 499
      participants for a mean +/- SD duration of 8.9 +/- 2.3 years and 5.2 +/- 1.9
      years, respectively. We tested associations between 8-OHdG concentrations and
      urinary albumin concentration (UAC) or eGFR at baseline, and the risk of ESRD or
      all-cause mortality during follow-up. Analyses were performed in pooled cohorts.
      RESULTS: The highest UAC (geometric mean [95% CI]) was observed in the third 8
      OHdG tertile (tertile 1, 9 [6, 13] mg/l; tertile 2, 10 [7, 16] mg/l; tertile 3,
      16 [10, 25] mg/l; p = 0.36 for tertile 1 vs tertile 2 and p = 0.003 for tertile 3
      vs tertile 1) after adjustment for potential confounding covariates. The lowest
      eGFR (mean [95% CI]) was observed in the third tertile (tertile 1, 87 [82, 93] ml
      min-1 1.73 m-2; tertile 2, 88 [82, 94] ml min-1 1.73 m-2; tertile 3, 74 [68, 80]
      ml min-1 1.73 m-2; p = 0.61 for tertile 1 vs tertile 2; p < 0.001 for tertile 3
      vs tertile 1). ESRD and death occurred in 48 and 64 individuals, respectively.
      The HR for ESRD, but not death, was higher in the third tertile than in the first
      (tertile 2 vs tertile 1, 1.45 [0.45, 5.04], p = 0.54; tertile 3 vs tertile 1,
      3.05 [1.16, 9.60], p = 0.02) after multiple adjustments.
      CONCLUSIONS/INTERPRETATION: Higher plasma concentrations of 8-OHdG were
      independently associated with increased risk of kidney disease in individuals
      with type 1 diabetes, suggesting that this marker can be used to evaluate the
      progression of diabetic kidney disease.

PMID- 29185013
TI  - Assessment of arterially hyper-enhancing liver lesions using virtual
      monoenergetic images from spectral detector CT: phantom and patient experience.
AB  - PURPOSE: To investigate a benefit from virtual monoenergetic reconstructions
      (VMIs) for assessment of arterially hyper-enhancing liver lesions in phantom and
      patients and to compare hybrid-iterative and spectral image reconstructions of
      conventional images (CI-IR and CI-SR). METHODS: All imaging was performed on a
      SDCT (Philips Healthcare, Best, The Netherlands). Images of a non-anthropomorphic
      phantom with a lesion-mimicking insert (containing iodine in water solution) and
      arterial-phase images from contrast-enhanced patient examinations were evaluated.
      VMIs (40-200 keV, 10 keV increment), CI-IR, and CI-SR were reconstructed using
      different strengths of image denoising. ROIs were placed in lesions,
      liver/matrix, muscle; signal-to-noise, contrast-to-noise, and lesion-to-liver
      ratios (SNR, CNR, and LLR) were calculated. Qualitatively, 40, 70, and 110 keV
      and CI images were assessed by two radiologists on five-point Likert scales
      regarding overall image quality, lesion assessment, and noise. RESULTS: In
      phantoms, SNR was increased threefold by VMI40keV compared with CI-IR/SR (5.8 +/-
      1.1 vs. 18.8 +/- 2.2, p <= 0.001), while no difference was found between CI-IR
      and CI-SR (p = 1). Denoising was capable of noise reduction by 40%. In total, 20
      patients exhibiting 51 liver lesions were assessed. Attenuation was the highest
      in VMI40keV, while image noise was comparable to CI-IR resulting in a threefold
      increase of CNR/LLR (CI-IR 1.3 +/- 0.8/4.4 +/- 2.0, VMI40keV: 3.8 +/- 2.7/14.2 +/
      7.5, p <= 0.001). Subjective lesion delineation was the best in VMI40keV image
      (p <= 0.01), which also provided the lowest perceptible noise and the best
      overall image quality. CONCLUSIONS: VMIs improve assessment of arterially hyper
      enhancing liver lesions since they increase lesion contrast while maintaining low
      image noise throughout the entire keV spectrum. These data suggest that to
      consider VMI screening after arterially hyper-enhancing liver lesions.

PMID- 29185014
TI  - Characterizing indeterminate liver lesions in patients with localized pancreatic
      cancer at the time of diagnosis.
AB  - BACKGROUND: In patients with newly diagnosed pancreatic cancer, the
      classification of indeterminate liver lesions is an unanswered clinical dilemma
      as misclassification of these lesions can impact the assignment of clinical stage
      and subsequent treatment planning. Our objective was to design a standardized
      classification system to more accurately define the risk of malignancy in
      indeterminate liver lesions. METHODS: In this retrospective study, patients with
      localized, non-metastatic pancreatic cancer were identified and pre-treatment
      computed tomography (CT) scans were evaluated for the presence or absence of
      liver lesions. Liver lesions were defined as definitely benign (1) or
      indeterminate (2). Indeterminate lesions were further sub-classified as either
      indeterminate probably benign (2B) or indeterminate possibly malignant (2M). The
      index liver lesion was evaluated on follow-up imaging for stability or
      unequivocal disease progression. RESULTS: From 2008 to 2015, 304 patients with
      localized, non-metastatic pancreatic cancer were identified and 125 (41%)
      patients had liver lesions. Of the 125 patients, the liver lesions in 35 (28%)
      were classified as definitely benign and in 90 (72%) patients they were
      classified as indeterminate. The 90 patients with indeterminate lesions included
      80 (89%) classified as indeterminate probably benign (2B) and 10 (11%) classified
      as indeterminate possibly malignant (2M). After a median follow-up of 56 weeks,
      no patient with a definitely benign lesion had metastatic disease progression of
      the index lesion. Of the 90 patients with indeterminate liver lesions, the index
      lesion progressed to unequivocal liver metastasis in 8 (9%) patients; 5 (6%) of
      the 80 lesions classified as indeterminate probably benign (2B), and 3 (30%) of
      the ten lesions classified as indeterminate possibly malignant (2M). The
      sensitivity of the classification system was 38% and the specificity was 91%. The
      positive predictive value was 30% and the negative predictive value was 94%.
      CONCLUSIONS: A significant proportion of patients with localized pancreatic
      cancer will have liver lesions identified at the time of diagnosis and most of
      these lesions will have indeterminate characteristics. A classification system
      which further stratifies indeterminate liver lesions by malignant potential can
      assist clinicians in determining optimal treatment plan and is associated with a
      high negative predictive value.

PMID- 29185015
TI  - Esophageal abnormalities in gastroesophageal reflux disease.
AB  - Fluoroscopic esophagography is a widely available, safe, and inexpensive test for
      detecting gastroesophageal reflux disease. In this article, we review the
      technique for performing a high-quality esophagram, including upright, double
      contrast views of the esophagus and cardia with high-density barium; prone,
      single-contrast views of the esophagus with low-density barium; and evaluation of
      gastroesophageal reflux. We then discuss the radiographic findings associated
      with gastroesophageal reflux disease, including esophageal dysmotility, reflux
      esophagitis, peptic strictures, and Barrett's esophagus. Finally, we consider the
      differential diagnosis for the various radiographic findings associated with this
      condition. When carefully performed and interpreted, the esophagram is a useful
      test for evaluating gastroesophageal reflux disease and its complications.

PMID- 29185016
TI  - The radiological myometrial appearance after cesarean section: is it associated
      with postpartum complications and subsequent delivery outcome?
AB  - PURPOSE: To evaluate whether the characteristics of the radiological uterine
      myometrial discontinuity (RMD) is associated with maternal-neonatal outcomes and
      post-cesarean section (CS) complications. A secondary aim was to describe the
      evolution of the CT uterine surgical incision and the related outcome of a
      subsequent trial of labor after cesarean (TOLAC). METHODS: Single center
      retrospective cohort study of CT scans was performed within 6 weeks from cesarean
      delivery. Demographic characteristics of patients were recorded (age, intrapartum
      fever, CS data, and hospital stay length). Abdominopelvic CT scans were performed
      using a multidetector CT (16 or 256 slice) with intravenous contrast material. CT
      analysis was performed by two radiologists in consensus. The RMD seen as low
      attenuation gap in expected incision site was assessed for: visualization,
      thickness, and presence of gas. Logistic regression analysis was fitted to assess
      the relationship of the delivery-CT time interval with the presence of RMD and
      gas. RESULTS: Of a total of 75,791 births during the study period there were 8775
      CS (11.6%). The study group consisted of 101 CTs in 84 woman after CS. RMD
      defined in 73 (72.2%) of all CT exams; the mean RMD thickness was 7 mm +/- 3.9,
      "RMD gas" observed in 15 (17.9%) of CT exams. RMD thickness or gas presence were
      strongly associated with a CS-1st CT exam time interval of less than 7 days, OR
      5.8 [CI 1.5-22.6], p = 0.010, but not with maternal, delivery, or neonatal
      characteristics. A subsequent successful vaginal birth was achieved in 75% of the
      patients with no uterine rupture, regardless of the RMD gas presence. CONCLUSION:
      RMD gas visualization on CT is not associated with febrile morbidity, cesarean
      characteristics, and subsequent TOLAC results. RMD gas is a normal post-operative
      finding and should not lead to changes in the postpartum delivery complication
      management or recommendations for the future mode of delivery.

PMID- 29185012
TI  - Systems biology of the IMIDIA biobank from organ donors and pancreatectomised
      patients defines a novel transcriptomic signature of islets from individuals with
      type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Pancreatic islet beta cell failure causes type 2 diabetes in
      humans. To identify transcriptomic changes in type 2 diabetic islets, the
      Innovative Medicines Initiative for Diabetes: Improving beta-cell function and
      identification of diagnostic biomarkers for treatment monitoring in Diabetes
      (IMIDIA) consortium ( www.imidia.org ) established a comprehensive, unique
      multicentre biobank of human islets and pancreas tissues from organ donors and
      metabolically phenotyped pancreatectomised patients (PPP). METHODS: Affymetrix
      microarrays were used to assess the islet transcriptome of islets isolated either
      by enzymatic digestion from 103 organ donors (OD), including 84 non-diabetic and
      19 type 2 diabetic individuals, or by laser capture microdissection (LCM) from
      surgical specimens of 103 PPP, including 32 non-diabetic, 36 with type 2
      diabetes, 15 with impaired glucose tolerance (IGT) and 20 with recent-onset
      diabetes (<1 year), conceivably secondary to the pancreatic disorder leading to
      surgery (type 3c diabetes). Bioinformatics tools were used to (1) compare the
      islet transcriptome of type 2 diabetic vs non-diabetic OD and PPP as well as vs
      IGT and type 3c diabetes within the PPP group; and (2) identify transcription
      factors driving gene co-expression modules correlated with insulin secretion ex
      vivo and glucose tolerance in vivo. Selected genes of interest were validated for
      their expression and function in beta cells. RESULTS: Comparative transcriptomic
      analysis identified 19 genes differentially expressed (false discovery rate
      <=0.05, fold change >=1.5) in type 2 diabetic vs non-diabetic islets from OD and
      PPP. Nine out of these 19 dysregulated genes were not previously reported to be
      dysregulated in type 2 diabetic islets. Signature genes included TMEM37, which
      inhibited Ca2+-influx and insulin secretion in beta cells, and ARG2 and PPP1R1A,
      which promoted insulin secretion. Systems biology approaches identified HNF1A,
      PDX1 and REST as drivers of gene co-expression modules correlated with impaired
      insulin secretion or glucose tolerance, and 14 out of 19 differentially expressed
      type 2 diabetic islet signature genes were enriched in these modules. None of
      these signature genes was significantly dysregulated in islets of PPP with
      impaired glucose tolerance or type 3c diabetes. CONCLUSIONS/INTERPRETATION: These
      studies enabled the stringent definition of a novel transcriptomic signature of
      type 2 diabetic islets, regardless of islet source and isolation procedure. Lack
      of this signature in islets from PPP with IGT or type 3c diabetes indicates
      differences possibly due to peculiarities of these hyperglycaemic conditions
      and/or a role for duration and severity of hyperglycaemia. Alternatively, these
      transcriptomic changes capture, but may not precede, beta cell failure.

PMID- 29185017
TI  - Incidence of Post-ablation Syndrome Following Image-Guided Percutaneous
      Cryoablation of Renal Cell Carcinoma: A Prospective Study.
AB  - PURPOSE: To prospectively evaluate the incidence of post-ablation syndrome (fever
      and flu-like symptoms) and impact on the quality of life in the first 10 days
      following percutaneous image-guided cryoablation for renal cell carcinoma (RCC).
      MATERIALS AND METHODS: A prospective study of all cryoablation procedures with
      biopsy proven RCC was conducted with institutional review board approval between
      08/2012 and 04/2016. Sixty-four patients (43 males and 21 females) underwent
      cryoablation. Mean age was 68 (range 24-86). A telephone questionnaire survey was
      conducted on days 1, 3, 5, 7 and 10 following cryoablation, and complications
      were recorded. Data collected included temperature, degree of flu-like symptoms,
      severity of pain, percentage of pain relief with analgesics, interference with
      general activity and with work (graded on a 0-10 Numeric Intensity Scale).
      RESULTS: Following cryoablation, six patients (9%) out of 64 developed post
      ablation syndrome. Thirty-three patients (52%) developed flu-like symptoms only,
      which completely resolved by day 10 in 25 patients (39%). One patient had pyrexia
      only, which was self- limiting by day 10. Twenty-four patients (38%) were
      asymptomatic. Pain (mean score = 2.1) and interference on general activities
      (mean score = 1.8) and work (mean score = 2) following cryoablation peaked on day
      3 and improved subsequently. Forty-six patients (72%) had 90-100% pain relief by
      day 10. No major complications were observed. CONCLUSION: The full spectrum of
      post-ablation syndrome following cryoablation occurs in approximately 9% of
      patients; however, 61% of patients experience flu-like symptoms in the first 10
      days, which are self-limiting.

PMID- 29185018
TI  - Evaluation of Resources Necessary for Provision of Trauma Care in Botswana: An
      Initiative for a Local System.
AB  - BACKGROUND: Developing countries face the highest incidence of trauma, and on the
      other hand, they do not have resources for mitigating the scourge of these
      injuries. The World Health Organization through the Essential Trauma Care (ETC)
      project provides recommendations for improving management of the injured and
      building up of systems that are effective in low-middle-income countries (LMICs).
      This study uses ETC project recommendations and other trauma-care guidelines to
      evaluate the current status of the resources and organizational structures
      necessary for optimal trauma care in Botswana; an African country with relatively
      good health facilities network, subsidized public hospital care and a functioning
      Motor Vehicle Accident fund covering road traffic collision victims. METHOD: A
      cross-sectional descriptive design employed convenience sampling for recruiting
      high-volume trauma hospitals and selecting candidates. A questionnaire,
      checklist, and physical verification of resources were utilized to evaluate
      resources, staff knowledge, and organization-of-care and hospital capabilities.
      Results are provided in plain descriptive language to demonstrate the findings.
      RESULTS: Necessary consumables, good infrastructure, adequate numbers of
      personnel and rehabilitation services were identified all meeting or exceeding
      ETC recommendations. Deficiencies were noted in staff knowledge of initial trauma
      care, district hospital capability to provide essential surgery, and the
      organization of trauma care. CONCLUSION: The good level of resources available in
      Botswana may be used to improve trauma care: To further this process, more
      empowering of high-volume trauma hospitals by adopting trauma-care
      recommendations and inclusive trauma-system approaches are desirable. The use of
      successful examples on enhanced surgical skills and capabilities, effective
      trauma-care resource management, and leadership should be encouraged.

PMID- 29185019
TI  - Correction to: 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  - The corrected order of the authors is as reflected in this erratum. Sebastian
      Suarez and Ayla Senay are co-second authors.

PMID- 29185020
TI  - The Positive Lymph Node Number and Postoperative N-Staging Used to Estimate
      Survival in Patients with Differentiated Thyroid Cancer: Results from the
      Surveillance, Epidemiology, and End Results Dataset (1988-2008).
AB  - BACKGROUND: Lymph node metastasis is important when evaluating the prognosis of
      patients with differentiated thyroid cancer (DTC). However, the current N-staging
      system cannot fully reflect the clinical significance of cervical lymph node
      metastasis in DTC. In this study, we employed Surveillance, Epidemiology, and End
      Results (SEER)-registered DTC cases with lymph node metastasis to determine
      whether the positive lymph node number (PLNN) could be used to improve
      stratification of patients in terms of survival. METHODS: We used the SEER
      dataset to identify all DTC patients with at least one positive cervical lymph
      node who were examined between 1988 and 2008. Multivariable modeling was used to
      compare cancer-specific survival (CSS) and overall survival (OS) and to calculate
      different PLNN cutoff points. RESULTS: In total, 14,359 pN + DTC patients
      identified in the SEER were included. In multivariate Cox regression analysis,
      the PLNN was significantly associated with both CSS and OS, whereas neither the
      lymph node ratio (LNR) nor the (numbers of) lymph nodes examined (LNE) were so
      associated. The highest C-index value (0.933) and the lowest AIC value (9362.687)
      obtained indicated that the PLNN better predicted the CSS of DTC than did the LNR
      or LNE. As the p values for both CSS and OS were minimized, and as the PLNN
      performed best when cases were grouped, PLNN cutoff points of 10 and 3/10
      efficiently stratified DTC patients into two and three levels, respectively.
      Based on the 3/10 trichotomy, the benefits of radioactive iodine (RAI) treatment
      were evaluated for each group. Such treatment afforded about a 10% survival
      benefit in patients with more than 10 lymph node metastases. CONCLUSIONS:
      Compared with the LNR and LNE under different statistical models, PLNN was
      superior in terms of DTC staging. A cutoff point of 3/10 was optimal for
      stratifying patients according to prognosis and was of clinical significance in
      terms of RAI treatment selection.

PMID- 29185022
TI  - Change and dispersion of QT interval during treatment with quetiapine extended
      release versus aripiprazole in children and adolescents with first-episode
      psychosis: results from the TEA trial.
AB  - OBJECTIVE: The aim of this study was to compare the effect of quetiapine extended
      release (ER) versus aripiprazole on corrected QT interval (QTc) and QT dispersion
      (QTd) in youths with first-episode psychosis. METHODS: Youths 12-17 years were
      randomized to quetiapine ER (daily dose range = 50 to 800 mg) or aripiprazole
      (daily dose range = 2.5 to 30 mg) in a 12-week double-blinded trial and examined
      at weeks 0, 4, and 12. Primary outcome was QTc change using Hodges formula
      (QTcH); secondary outcomes included QTcH > 450 ms, QTcH > 500 ms, QTcH change >
      60 ms, QTd, and heart rate (HR). RESULTS: Among 113 randomized youths, follow-up
      ECG was available for 93 patients (82.3%) (age = 15.8 +/- 1.3 years, males =
      34.4%, schizophrenia = 67.7%). Quetiapine ER treatment (n = 47) was associated
      with a significant increase in QTcH of + 6.8 +/- 20.2 ms (p = 0.025), while the
      change from baseline in patients receiving aripiprazole (n = 46) was non
      significant (- 3.4 +/- 18.9 ms, p = 0.225). One patient in the quetiapine ER
      group had a QTcH change of + 62.3 ms. Age, sex, smoking, body mass index, and
      concomitant medication were not significantly associated with QTcH change, but
      higher baseline potassium was correlated to higher QTcH change in the quetiapine
      ER group. The HR increased significantly with quetiapine ER (+ 11.0 +/- 14.2 bpm,
      p < 0.001) but not with aripiprazole (- 0.8 +/- 12.0 bpm, p = 0.643). QTd did not
      significantly change with quetiapine ER or aripiprazole. CONCLUSION: QTcH and HR
      increased significantly with quetiapine ER, although changes were small and
      likely not clinically significant in otherwise healthy patients. QTcH and HR were
      unchanged with aripiprazole. No significant change in QTd was seen.
      ClinicalTrials.gov: NCT01119014, EudraCT: 2009-016715-38.

PMID- 29185021
TI  - Surgical Training and Standardised Management Guidelines Improved the 30-Day
      Complication Rate After Abdominoplasty for Massive Weight Loss.
AB  - BACKGROUND: An increasing number of patients need reconstructive surgery after
      massive weight loss. The hypothesis was that surgical experience together with
      standardised management guidelines significantly decreases early complication
      rates after abdominoplasty for massive weight loss. The primary aim was to assess
      the 30-day complication rate after abdominoplasty following increased surgical
      training and experience. The secondary aim was to assess whether optimised
      management guidelines have an impact on the complication rate and patient safety.
      METHODS: The outcome of 69 consecutive abdominoplasties operated by surgeons in
      2011 (Group A) and 70 consecutive patients operated by plastic surgeons in 2010
      2012 (Group B) was compared. Another Group of 70 consecutive patients operated by
      surgeons in 2013-2014 (Group C) was assessed since standardised guidelines for
      pre- and post-operative treatments and refinement of surgical technique had been
      introduced. The same surgeons participated in operations of Groups A and C. chi 2
      test and Fisher's exact test were applied to dichotomous data. Logistic
      regression test and ANOVA were used. RESULTS: Group C had more comorbidities and
      was significantly older. 48 patients in Group A (70%), 31 in Group B (44%) and 13
      patients in Group C (19%) had early complications. A significantly decreased rate
      of complications occurred with improved guidelines and surgical training and
      experience. (A vs. C p < 0.001 and A vs. B p = 0.008). CONCLUSIONS: Our results
      indicate that the rate of early complications after abdominoplasty for massive
      weight loss can be significantly reduced with improved surgical experience and
      standardised management guidelines. Registered at Clinical Trial.gov (ID:
      NCT02679391).

PMID- 29185023
TI  - Sex differences in the association of alcohol with cognitive decline and brain
      pathology in a cohort of octogenarians.
AB  - RATIONALE: The beneficial effects of moderate alcohol may differ in aging men
      versus women. OBJECTIVES: Cognitive and functional decline and neuropathology
      were investigated in a cohort of aging men and women with diverse alcohol
      histories. METHODS: Non-demented (Clinical Dementia Rating (CDR) of <= 0.5 and a
      Mini-Mental State Examination (MMSE) score of > 24), autonomously living
      participants were tracked in longitudinal aging studies to examine self-report
      and objective tests of rates of decline in a cohort (n = 486) of octogenarians.
      Neurofibrillary tangles (NFTs; Braak stage) and neuritic plaques (NPs) were
      staged at autopsy in a subset of participants (n = 149) using current standard
      neuropathologic diagnostic criteria. RESULTS: Moderate drinking men had an
      attenuated rate of decline compared to rare/never drinkers and women on the MMSE
      and CDR sum of boxes. In contrast, moderate drinking women had a reduced rate of
      decline only in the Logical Memory Delayed Recall Test (LMDR) compared to
      rare/never drinkers and men. Moderate alcohol consumption was associated with a
      reduction in the incidence of advanced (stages 5-6) Braak NFT stage in men (p <
      0.05), with no effect in women. CONCLUSIONS: In this cohort, men experienced a
      broader range of beneficial effects associated with alcohol. Alcohol's effects
      may differ in men and women in important ways that suggest a narrower beneficial
      window.

PMID- 29185024
TI  - Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate
      fluoride toxicity in ameloblasts responsible for enamel formation.
AB  - Low-dose fluoride is an effective caries prophylactic, but high-dose fluoride is
      an environmental health hazard that causes skeletal and dental fluorosis.
      Treatments to prevent fluorosis and the molecular pathways responsive to fluoride
      exposure remain to be elucidated. Previously we showed that fluoride activates
      SIRT1 as an adaptive response to protect cells. Here, we demonstrate that
      fluoride induced p53 acetylation (Ac-p53) [Lys379], which is a SIRT1
      deacetylation target, in ameloblast-derived LS8 cells in vitro and in enamel
      organ in vivo. Here we assessed SIRT1 function on fluoride-induced Ac-p53
      formation using CRISPR/Cas9-mediated Sirt1 knockout (LS8Sirt/KO) cells or
      CRISPR/dCas9/SAM-mediated Sirt1 overexpressing (LS8Sirt1/over) cells. NaF (5 mM)
      induced Ac-p53 formation and increased cell cycle arrest via Cdkn1a/p21
      expression in Wild-type (WT) cells. However, fluoride-induced Ac-p53 was
      suppressed by the SIRT1 activator resveratrol (50 uM). Without fluoride, Ac-p53
      persisted in LS8Sirt/KO cells, whereas it decreased in LS8Sirt1/over. Fluoride
      induced Ac-p53 formation was also suppressed in LS8Sirt1/over cells. Compared to
      WT cells, fluoride-induced Cdkn1a/p21 expression was elevated in LS8Sirt/KO and
      these cells were more susceptible to fluoride-induced growth inhibition. In
      contrast, LS8Sirt1/over cells were significantly more resistant. In addition,
      fluoride-induced cytochrome-c release and caspase-3 activation were suppressed in
      LS8Sirt1/over cells. Fluoride induced expression of the DNA double strand break
      marker gammaH2AX in WT cells and this was augmented in LS8Sirt1/KO cells, but was
      attenuated in LS8Sirt1/over cells. Our results suggest that SIRT1 deacetylates Ac
      p53 to mitigate fluoride-induced cell growth inhibition, mitochondrial damage,
      DNA damage and apoptosis. This is the first report implicating Ac-p53 in fluoride
      toxicity.

PMID- 29185025
TI  - Highlight report: gene dose response in N-acetylation capacity.

PMID- 29185026
TI  - Ballistic impacts on an anatomically correct synthetic skull with a surrogate
      skin/soft tissue layer.
AB  - The aim of this work was to further develop a synthetic model of ballistic head
      injury by the addition of skin and soft tissue layers to an anatomically correct
      polyurethane skull filled with gelatine 10% by mass. Six head models were
      impacted with 7.62 x 39 mm full metal jacket mild steel core (FMJ MSC) bullets
      with a mean velocity of 652 m/s. The impact events were filmed with high-speed
      cameras. The models were imaged pre- and post-impact using computed tomography.
      The models were assessed post impact by two experienced Home Office pathologists
      and the images assessed by an experienced military radiologist. The findings were
      scored against real injuries. The entry wounds, exit wounds and fracture patterns
      were scored positively, but the synthetic skin and soft tissue layer was felt to
      be too extendable. Further work is ongoing to address this.

PMID- 29185027
TI  - Identification of genes associated with susceptibility to Mycobacterium avium
      ssp. paratuberculosis (Map) tissue infection in Holstein cattle using gene set
      enrichment analysis-SNP.
AB  - Multiple genome-wide association analyses have investigated susceptibility to
      bovine paratuberculosis, but few loci have been identified across independent
      cattle populations. A SNP-based gene set enrichment analysis (GSEA-SNP) allows
      expanded identification of genes with moderate effects on a trait through the
      enrichment of gene sets instead of identifying only few loci with large effects.
      Therefore, the objective of this study was to identify genes that were moderately
      associated with Mycobacterium avium ssp. paratuberculosis (Map) tissue infection
      using GSEA-SNP in Holstein cattle from the Pacific Northwest (PNW; n = 205) and
      from the PNW and Northeast (PNW+NE; n = 245) which were previously genotyped with
      the Illumina BovineSNP50 BeadChip. The GSEA-SNP utilized 4389 gene sets from five
      databases. For each annotated gene in the UMD3.1 assembly (n = 19,723), the most
      significant SNP within each gene and its surrounding region (10 kb up- and
      downstream) was selected as a proxy for that gene. Any gene set with a normalized
      enrichment score > 2.5 was considered enriched. Thirteen gene sets (8 PNW GSEA
      SNP; 5 PNW+NE) were enriched in these analyses and all have functions that relate
      to nuclear factor kappa beta. Nuclear factor kappa beta is critical to gut immune
      responses, implicated in host immune responses to other mycobacterial diseases,
      and has established roles in inflammation as well as cancer. Gene sets and genes
      moderately associated with Map infection could be used in genomic selection to
      allow producers to select for less susceptible cattle, lower the prevalence of
      the disease, and reduce economic losses.

PMID- 29185029
TI  - European status on temporal bone training: a questionnaire study.
AB  - PURPOSE: In otorhinolaryngology training, introduction to temporal bone surgery
      through hands-on practice on cadaveric human temporal bones is the gold-standard
      training method before commencing supervised surgery. During the recent decades,
      the availability of such specimens and the necessary laboratory facilities for
      training seems to be decreasing. Alternatives to traditional training can consist
      of drilling artificial models made of plaster or plastic but also virtual reality
      (VR) simulation. Nevertheless, the integration and availability of these
      alternatives into specialist training programs remain unknown. METHODS: We
      conducted a questionnaire study mapping current status on temporal bone training
      and included responses from 113 departments from 23 countries throughout Europe.
      RESULTS: In general, temporal bone training during residency in ORL is organized
      as in-house training, or as participation in national or international temporal
      bone courses or some combination hereof. There are considerable differences in
      the availability of training facilities for temporal bone surgery and the number
      of drillings each ORL trainee can perform. Cadaveric dissection is still the most
      commonly used training modality. CONCLUSIONS: VR simulation and artificial models
      are reported to be used at many leading training departments already. Decreasing
      availability of cadavers, lower costs of VR simulation and artificial models, in
      addition to established evidence for a positive effect on the trainees'
      competency, were reported as the main reasons. Most remaining departments expect
      to implement VR simulation and artificial models for temporal bone training into
      their residency programs in the near future.

PMID- 29185028
TI  - Significant association of the cytokine variants with head and neck cancer risk:
      evidence from meta-analysis.
AB  - AIM: To evaluate the possible relevance of the IL-18-137 G>C (rs187238), IL-18
      607 C>A (rs1946518) and IL-4-590 C>T (rs2243250) polymorphisms to the genetic
      susceptibility of head and neck cancer. METHODS: Data were retrieved from PubMed,
      EMBASE, Web of Science and CNKI databases, and the results were independently
      analysed by two reviewers using Stata 14.0 software. RESULTS: After searching for
      and assessing the literature, a total of thirteen studies involving 2,959
      patients newly diagnosed as head and neck cancer and 3,622 controls from healthy
      donors were analysed. The results suggested that a strong relationship between
      patients and healthy controls was observed in the IL-18-137 G>C polymorphism in
      consistence with the result (CC vs. GG + GC: OR = 1.63, P = 0.004; CC vs. GG: OR
      = 1.82, P = 0.001). When stratified by cancer type, ethnicity and the source of
      control samples, significant and elevated risks were obtained in the genetic
      susceptibility to Asian patients with NPC in all genetic models and in those
      studies using the PCR-RFLP test method. In addition, comparable results were
      obtained for the IL-18-607 C>A polymorphism, especially for Asian patients with
      NPC. CONCLUSIONS: It should be a potential association between IL-18 variants and
      nasopharyngeal carcinoma. Furthermore, IL-18 gene variants might be considered as
      a critical role in predicting the occurrence of nasopharyngeal carcinoma in Asian
      population. However, the IL-4-590 C>T polymorphism does not influence the
      development of head and neck cancer.

PMID- 29185030
TI  - First detection and molecular identification of Entamoeba bovis from Japanese
      cattle.
AB  - Thus far, Entamoeba species have been classified based on morphology such as the
      number of nuclei in mature cysts and their hosts. Using recently developed
      molecular tools, ruminant Entamoeba spp. are currently classified into four
      species/genotypes: E. bovis and Entamoeba ribosomal lineages (RL) 1, 2, and 4.
      However, the distribution or pathogenicity of ruminant Entamoeba has not been
      well documented. In the present study, we examined a total of 25 fecal and seven
      environmental samples collected from six farms in Japan from 2016 to 2017 by the
      floatation method and PCR and sequencing analyses. Consequently, we detected
      Entamoeba cysts in 18 of 25 cattle samples and four of the seven environmental
      samples, including soil and drinking water, by microscopic examinations. In
      sequential examinations, Entamoeba-positive cattle were found to shed cysts
      without any clinical symptoms for more than 8 months. By PCR for molecular
      identification, isolates in ten cattle and one soil sample were successfully
      sequenced and formed a cluster of E. bovis, which was separated from those of
      other Entamoeba species/genotypes such as RL1-4 in phylogenetic analysis. To our
      knowledge, this is the first report about E. bovis in Japan, and our results may
      implicate that E. bovis is not pathogenic.

PMID- 29185031
TI  - Amplifying and broadening the cytotoxic profile of quercetin in cancer cell lines
      through bioconjugation.
AB  - Quercetin is a flavonoid presenting cytotoxicity against different cancer cell
      lines. We hypothesized that its core could serve as a scaffold for generating
      more potent compounds. A quercetin-alanine bioconjugate was synthesized, its
      cellular internalization was monitored through confocal microscopy and its
      cytotoxic activity was explored against ten different cell lines. The
      bioconjugate consistently illustrated enhanced cytotoxic activity with respect to
      the parent compound. A threefold enhancement in its cytotoxicity was revealed for
      HeLa, A549, MCF-7 and LNCaP cells. In silico studies suggested that quercetin
      alanine possesses enhanced binding affinity to human estrogen receptor alpha
      corroborating to its activity to MCF-7, overexpressing this receptor.
      Spectrofluorimetric, calorimetric and in silico studies revealed that quercetin
      alanine binds primarily to Sudlow site I of serum albumin mainly through hydrogen
      bonding. Through this array of experiments we discovered that the specific
      compound bears a more refined pharmaceutical profile in contrast to quercetin in
      terms of cytotoxicity, while at the same time preserves its affinity to serum
      albumin. Natural products could thus offer a potent scaffold to develop
      bioconjugates with amplified therapeutic window.

PMID- 29185032
TI  - Thirteen decades of peptide synthesis: key developments in solid phase peptide
      synthesis and amide bond formation utilized in peptide ligation.
AB  - A historical overview of peptide chemistry from T. Curtius to E. Fischer to M.
      Bergmann and L. Zervas is first presented. Next, the fundamentals of peptide
      synthesis with a focus on solid phase peptide synthesis by R. B. Merrifield are
      described. Immobilization strategies to attach the first amino acid to the resin,
      coupling strategies in stepwise peptide chain elongation, and approaches to
      synthesize difficult peptide sequences are also shown. A brief comparison between
      tert-butyloxycarbonyl (Boc)/benzyl (Bzl) strategy and 9-fluorenylmethoxycarbonyl
      (Fmoc)/tert-butyl (t -Bu) strategy utilized in solid phase peptide synthesis is
      given with an emphasis on the latter. Finally, the review focuses on the
      discovery and development of peptide ligation and the latest advances in this
      field including native amide bond formation strategies, these include the native
      chemical ligation, alpha-ketoacid-hydroxylamine ligation, and serine/threonine
      ligation which are the most commonly used chemoselective ligation methods that
      provide amide bond at the ligation site. This review provides an overview of the
      literature concerning the most important advances in the chemical synthesis of
      proteins and peptides covering the period from 1882 to 2017.

PMID- 29185033
TI  - Transcriptomic and proteomic feature of salt stress-regulated network in
      Jerusalem artichoke (Helianthus tuberosus L.) root based on de novo assembly
      sequencing analysis.
AB  - MAIN CONCLUSION: Ribosome activation and sugar metabolic process mainly act on
      the regulation of salt tolerance in the bioenergy crop Helianthus tuberosus L. as
      dissected by integrated transcriptomic and proteomic analyses. Helianthus
      tuberosus L. is an important halophyte plant that can survive in saline-alkali
      soil. It is vitally necessary to build an available genomic resource to
      investigate the molecular mechanisms underlying salt tolerance in H. tuberosus.
      De novo assembly and annotation of transcriptomes were built for H. tuberosus
      using a HiSeq 4000 platform. 293,823 transcripts were identified and annotated
      into 190,567 unigenes. In addition, iTRAQ-labeled quantitative proteomics was
      carried out to detect global protein profiling as a response to salt stress.
      Comparative omics analysis showed that 5432 genes and 43 proteins were
      differentially expressed in H. tuberosus under salt stress, which were enriched
      in the following processes: carbohydrate metabolism, ribosome activation and
      translation, oxidation-reduction and ion binding. The reprogramming of transcript
      and protein works suggested that the induced activity of ribosome and sugar
      signaling may endue H. tuberosus with salt tolerance. With high-quality
      sequencing and annotation, the obtained transcriptomics and proteomics provide a
      robust genomic resource for dissecting the regulatory molecular mechanism of H.
      tuberosus in response to salt stress.

PMID- 29185034
TI  - Molecular docking simulation on the interactions of laccase from Trametes
      versicolor with nonylphenol and octylphenol isomers.
AB  - The biodegradation of nonylphenol (NP) and octylphenol (OP) isomers by laccase
      has attracted increasing concerns. However, the interaction mechanism between
      these isomers and laccase remains unclear, especially for fungal laccase. In this
      work, molecular docking was employed to study this issue. The results indicated
      that the structural characteristic of alkyl chain (position and branching degree)
      affected the interactions between Trametes versicolor (T. versicolor) laccase and
      isomers. The binding affinity between them was closely related to the position
      and branching degree of alkyl chain in isomers. The binding affinities between
      linear isomers and T. versicolor laccase were para-position < meta-position <
      ortho-position. For selected branched 4-NP, the isomers with bulky alpha
      substituent in alkyl chain had higher binding affinities. In addition,
      hydrophobic contacts between T. versicolor laccase and NP or OP isomers were
      necessary, while H-bonds were optional. The isomers with similar structure may
      have more common residues involved in hydrophobic contacts. The H-bonds of
      selected NPs and OPs were all connected with phenolic hydroxyl. These findings
      provide an insight into detailed interaction mechanism between T. versicolor
      laccase and isomers of NP and OP. It is helpful to broaden the knowledge of
      degradation technology of NPs and OPs and provide theoretical basis on biological
      remediation of these contaminants.

PMID- 29185035
TI  - Relationship Between Frequency of Spontaneous Swallowing and Salivary Substance P
      Level in Patients with Acute Stroke.
AB  - The frequency of spontaneous swallowing is useful for screening of dysphagia in
      acute stroke. Low levels of substance P (SP) in saliva attenuate the swallowing
      reflex. The aim of this study was to determine the relationship between the
      frequency of spontaneous swallowing and salivary SP levels. In 40 subjects,
      saliva was collected within 72 h after stroke onset and salivary SP levels were
      measured using ELISA kit at a later date. The frequency of spontaneous swallowing
      was measured over 1 h using a microphone placed on the neck. Pneumonia was
      diagnosed by the presence of pyrexia and at least two respiratory problems of
      four categories (sputum, cough or breathing pattern, breath sound, and gas
      change). The presence of detectable levels of SP in the saliva was confirmed in
      17 patients (high SP group), whereas the level was below the detection limit of
      the ELISA kit in 23 patients (low SP group). The frequency of spontaneous
      swallowing was significantly lower in low SP group (16.1 +/- 11.6 per hour) than
      in the high SP group (30.4 +/- 20.4, p = 0.016). As the result of multiple
      regression analysis, salivary SP levels were correlated with frequency of
      spontaneous swallowing independently of age, NIHSS, and GCS. The incidence of
      pneumonia was significantly higher in the low than high SP group (p < 0.001). In
      conclusion, the frequency of spontaneous swallowing was decreased in acute stroke
      patients with low salivary SP levels. Salivary SP levels can be potentially a
      useful biomarker of risk of stroke-associated pneumonia in the acute stage.

PMID- 29185046
TI  - Functional outcomes after removal of hardware in patellar fracture: are we
      helping our patients?
AB  - PURPOSE: Functional outcomes after Open Reduction Internal Fixation (ORIF) of the
      patella are variable. Common complications of patella ORIF include persistent
      anterior knee pain, limited range of motion and symptomatic hardware. The purpose
      of this study was to evaluate if removal of hardware is beneficial to symptomatic
      patients after patellar fracture fixation. METHODS: Patients who presented to our
      institution between December 2006 and November 2014 with patella fractures
      treated with ORIF were eligible for inclusion. Patella ORIF was performed using
      (1) K-wires (KW) with a tension band construct or (2) Cannulated Screws (CS) with
      a tension band construct. Radiological analyses included (1) AO classification
      and (2) measurements of prominent hardware length. Patient medical charts were
      reviewed for demographic and intraoperative data as well as peri/postoperative
      complications. All patients completed the SF-12 score, visual analog scale,
      Kujala score, Lysholm score and questionaries' regarding return to previous
      activity levels. RESULTS: Forty-seven patients met the inclusion criteria. The
      average time from fracture fixation to removal of hardware was 15.8 (SD +/- 14.9)
      months. The mean follow-up was 43.1 (SD +/- 27.1) months. Patella fixation was
      accomplished using tension band constructs with KW in 28 patients (59.5%) or with
      CS in 19 patients (40.5%). Patient reported quality of life and pain outcomes
      improved significantly after removal of hardware (p = 0.001, and p = 0.002
      respectively). Functional outcome scores (Kujala and Lysholm) did not improve
      significantly after hardware removal in the KW or CS groups. Significantly more
      patients in the KW group returned to pre-injury activity (p = 0.005).
      CONCLUSIONS: Hardware removal after patella ORIF significantly improves patient
      reported pain and quality of life outcomes but not functional outcomes. Patients
      should be counseled regarding the expected outcome of hardware removal following
      patella ORIF and diabetic patients should be given special consideration before
      undergoing this procedure.

PMID- 29185047
TI  - PID temperature controller in pig nursery: spatial characterization of thermal
      environment.
AB  - The use of enhanced technologies of temperature control can improve the thermal
      conditions in environments of livestock facilities. The objective of this study
      was to evaluate the spatial distribution of the thermal environment variables in
      a pig nursery with a heating system with two temperature control technologies
      based on the geostatistical analysis. The following systems were evaluated:
      overhead electrical resistance with Proportional, Integral, and Derivative (PID)
      controller and overhead electrical resistance with a thermostat. We evaluated the
      climatic variables: dry bulb temperature (Tbs), air relative humidity (RH),
      temperature and humidity index (THI), and enthalpy in the winter, at 7:00, 12:00,
      and 18:00 h. The spatial distribution of these variables was mapped by kriging.
      The results showed that the resistance heating system with PID controllers
      improved the thermal comfort conditions in the pig nursery in the coldest hours,
      maintaining the spatial distribution of the air temperature more homogeneous in
      the pen. During the hottest weather, neither system provided comfort.

PMID- 29185045
TI  - Preoperative chronic kidney disease is predictive of oncological outcome of
      radical cystectomy for bladder cancer.
AB  - PURPOSE: To evaluate the impact of preoperative chronic kidney disease (CKD) on
      oncological outcomes after radical cystectomy (RC) for bladder cancer. METHODS:
      We reviewed the medical records of patients with urothelial bladder carcinoma who
      underwent RC with curative intent at seven hospitals between 1990 and 2013. After
      excluding patients with a history of upper urinary tract urothelial cancer or
      neoadjuvant chemotherapy, we analyzed 594 cases for the study. Preoperative
      estimated glomerular filtration rate (eGFR) was calculated using the three
      variable Japanese equation for GFR estimation from serum creatinine level and
      age. Patients were divided into four groups of different CKD stages based on eGFR
      values (mL/min/1.73 m2), i.e., >= 60 (CKD stages G1-2), 45-60 (G3a), 30-45 (G3b),
      and < 30 (G4-5). Survival was estimated using the Kaplan-Meier method. Univariate
      and multivariate Cox proportional hazards regression analyses addressed survivals
      after RC. RESULTS: Median age of patients was 67 years. Patients were classified
      into CKD stages: G1-2 (n = 388; 65.3%), G3a (n = 122; 20.5%), G3b (n = 51; 8.6%),
      and G4-5 (n = 33; 5.6%). During a median follow-up of 4.0 years, 200 and 164
      patients showed cancer progression and died of bladder cancer, with the 5-year
      progression-free survival (PFS) and cancer-specific survival (CSS) of 64.9 and
      70.2%, respectively. On multivariate analyses, CKD stages of G3b or greater,
      advanced pT stage, lymph node metastasis, and positive lymphovascular invasion
      were independent poor prognostic factors for PFS and CSS. CONCLUSIONS: We
      demonstrated that the advanced preoperative CKD stage was significantly
      associated with poor oncological outcomes of the bladder cancer after RC.

PMID- 29185048
TI  - Impaired left ventricular diastolic function is related to the formation of left
      ventricular apical thrombus in patients with acute anterior myocardial
      infarction.
AB  - Left ventricular (LV) apical thrombus is a clinically important complication
      which can cause systemic embolization in patients with anterior acute myocardial
      infarction (AMI). Systolic dysfunction has been a risk factor for developing LV
      apical thrombus in AMI patients. However, the role of diastolic dysfunction in
      the development of LV apical thrombus in these patients is still unknown. We
      performed this study to evaluate whether diastolic dysfunction can influence the
      development of LV apical thrombus in anterior AMI patients. We retrospectively
      analyzed all consecutive anterior AMI patients with available echocardiographic
      images within 1 month from January 2005 to April 2016. After gathering clinical
      characteristics from their medical records, systolic and diastolic functions were
      analyzed from digitally stored echocardiographic images. We included a total of
      1045 patients (748 males, mean age 64 +/- 12 years) with anterior AMI, and 494
      (47%) were diagnosed as STEMI. The incidence of LV apical thrombus was 3.3%
      (34/1045). The LV apical thrombus group had larger LV diastolic dimension, larger
      LV diastolic and systolic volumes, and lower LVEF than the no LV thrombus group.
      The LV apical thrombus group showed higher mitral E velocity over mitral annular
      E' velocity ratio, an indicator of LV end-diastolic pressure (P < 0.001). In the
      LV apical thrombus group, the incidence of grade 2 diastolic dysfunction (32 vs
      12%, P = 0.001) and grade 3 diastolic dysfunction (26 vs 2%, P < 0.001) were
      significantly higher than in the no LV apical thrombus group. The presence of
      more than grade 2 diastolic dysfunction, LVEF and presence of LV apical aneurysm
      were statistically significant factors associated with LV apical thrombus after
      the multivariate analysis. In conclusion, along with LV systolic dysfunction and
      LV apical aneurysm, LV diastolic dysfunction was also related with the presence
      of LV apical thrombus in patients with anterior AMI.

PMID- 29185049
TI  - A Radial Pillar Device (RAPID) for continuous and high-throughput separation of
      multi-sized particles.
AB  - Pillar-based microfluidic sorting devices are preferred for isolation of rare
      cells due to their simple designs and passive operation. Dead-end pillar filters
      can efficiently capture large rare cells, such as, circulating tumor cells
      (CTCs), nucleated red blood cells (NRBCs), CD4 cells in HIV patients, etc., but
      they get clogged easily. Cross flow filters are preferred for smaller rare
      particles (e.g. separating bacteria from blood), but they need additional buffer
      inlets and a large device footprint for efficient operation. We have designed a
      new microparticle separation device i.e. Ra dial Pi llar D evice (RAPID) that
      combines the advantages of dead-end and cross flow filters. RAPID can
      simultaneously isolate both large and small rare particles from a mixed
      population, while functioning for several hours without clogging. We have
      achieved simultaneous separation of 10 MU m and 2 MU m polystyrene particles from
      a mixture of 2 MU m, 7 MU m and 10 MU m particles. RAPID achieved average
      separation purity and recovery in excess of ~90%. The throughput of our device
      (~3ml/min) is 10 and 100 times higher compared to cross flow and dead-end filters
      respectively, thereby justifying the name RAPID.

PMID- 29185050
TI  - Practically applicable nerve ultrasound models for the diagnosis of axonal and
      demyelinating hereditary motor and sensory neuropathies (HMSN).
AB  - PURPOSE: To develop specific diagnostic ultrasound (US) models for hereditary
      motor and sensory neuropathies (HMSN) in patients with primarily demyelinating or
      axonal polyneuropathies (PNP) according to standard nerve conduction studies
      (NCS) criteria. METHODS: Single-centre, examiner-blinded cross-sectional study in
      acquired PNP (consecutive recruitment strategy) and HMSN patients (convenience
      sample). Allocation into demyelinating or axonal phenotype via easily applicable
      NCS criteria. Assessment of single measurements by receiver-operating curve (ROC)
      analysis, development of diagnostic models based on the best measurement values
      in ROC. RESULTS: Of 85 enrolled subjects, 53 (62%) had HMSN and 32 (38%) acquired
      PNPs, and 60 subjects (71%) had demyelinating and 25 (29%) axonal PNP. ROC area
      under the curve of means of the z-transformed 5 best measurement values was 0.87
      for demyelinating and 0.99 for axonal HMSN. Diagnostic models showed high
      accuracy for both demyelinating (84% sensitivity, 86% specificity) and axonal
      HMSN (100% sensitivity and specificity). As a measure of variability of
      morphologic changes, standard deviations of z-transformed measurements were
      compared for acquired PNP and HMSN. In contrast to previous reports of more
      homogenous nerve enlargements in HMSN, standard deviations were higher in HMSN
      than in acquired PNP. Additionally, the performance of previously published
      models for the diagnosis of HMSN in demyelinating PNP was compared. Previously
      published models showed lower sensitivities (50-58%), but comparable
      specificities (91-100%) when applied to NCS-criteria defined demyelinating PNP
      group. CONCLUSION: Diagnostic ultrasound models for HMSN in patients with
      demyelinating or axonal neuropathies show high accuracy and can contribute to
      differential diagnosis in clinical routine.

PMID- 29185051
TI  - Holography microscopy as an artifact-free alternative to phase-contrast.
AB  - Artifact-free microscopic images represent a key requirement of multi-parametric
      image analysis in modern biomedical research. Holography microscopy (HM) is one
      of the quantitative phase imaging techniques, which has been finding new
      applications in life science, especially in morphological screening, cell
      migration, and cancer research. Rather than the classical imaging of absorbing
      (typically stained) specimens by bright-field microscopy, the information about
      the light-wave's phase shifts induced by the biological sample is employed for
      final image reconstruction. In this comparative study, we investigated the
      usability and the reported advantage of the holography imaging. The claimed halo
      free imaging was analyzed compared to the widely used Zernike phase-contrast
      microscopy. The intensity and phase cross-membrane profiles at the periphery of
      the cell were quantified. The intensity profile for cells in the phase-contrast
      images suffers from the significant increase in intensity values around the cell
      border. On the contrary, no distorted profile is present outside the cell
      membrane in holography images. The gradual increase in phase shift values is
      present in the internal part of the cell body projection in holography image.
      This increase may be related to the increase in the cell internal material
      according to the dry mass theory. Our experimental data proved the halo-free
      nature of the holography imaging, which is an important prerequisite of the
      correct thresholding and cell segmentation, nowadays frequently required in high
      content screening and other image-based analysis. Consequently, HM is a method of
      choice whenever the image analysis relies on the accurate data on cell
      boundaries.

PMID- 29185054
TI  - Vacuum extraction in low birth weight (< 2500 g) neonates.
AB  - PURPOSE: To evaluate the impact of vacuum extraction on birth injuries among low
      birth weight neonate (2000-2499 g). METHODS: Retrospective cohort study of women
      with singleton pregnancies > 34 weeks, birth weight of 2000-3500 g, undergoing
      vacuum extraction, between 2007 and 2014. Outcomes were compared between neonates
      who weighed 2000-2499 g and 2500-3500 g. RESULTS: Out of 62,102 deliveries, 5064
      (8.2%) met the inclusion criteria, of which 269 (5.3%) neonates were included in
      the 2000-2499 g group. In this group, gestational age at delivery was lower, the
      rate of preeclampsia without and with severe features was higher, the rate of
      induction of labor was higher as was the rate of intermediate/abnormal fetal
      heart rate tracings as an indication for vacuum extraction (46.2% vs. 28.0%, P <
      0.001). No difference was found with regards to birth injuries (2.6% vs. 3.5%, P
      = 0.44). The rate of composite adverse outcomes other than birth injuries was
      higher in the 2000-2499 g group (13.0% vs. 9.1%, P = 0.03). Each additional 250 g
      in birth weight had an increased OR of 1.36 for birth injuries. CONCLUSION:
      Vacuum extraction of neonates weighing 2000-2499 g seems to be as safe as vacuum
      extractions of neonates weighing 2500-3500 g in term of birth injuries.

PMID- 29185052
TI  - Functional status mediates the association between peripheral neuropathy and
      health-related quality of life in individuals with diabetes.
AB  - AIMS: To examine differences in health-related quality of life (HRQoL) between
      patients with and without diabetic peripheral neuropathy (DPN), and whether these
      differences can be explained by functional deficits. METHODS: This was a cross
      sectional study of 160 patients with type 2 diabetes mellitus, 80 with DPN and 80
      without. Assessments included HRQoL (health utility score derived from EQ-5D-5L),
      functional status measurements [muscle strength, timed up and go (TUG), five
      times sit-to-stand (FTSTS), functional reach, body sway velocity] and self
      reported balance confidence [Activities-specific Balance Confidence (ABC) scale].
      RESULTS: Mean utility scores were 0.67 +/- 0.14 and 0.77 +/- 0.16 in patients
      with and without DPN, respectively (p < 0.001). Patients with DPN had lower great
      toe extensor strength (6.4 +/- 1.8 vs 7.6 +/- 2.8 lbs, p = 0.001), greater body
      sway velocity (2.40 +/- 1.31 vs 1.90 +/- 0.52 mm/s, p = 0.002), slower TUG (12.1
      +/- 4.6 vs 10.1 +/- 2.3 s, p < 0.001) and FTSTS (15.8 +/- 5.8 vs 13.9 +/- 5.4 s,
      p = 0.03) scores, and lower ABC score (73.4 +/- 21.3 vs 82.6 +/- 16.9, p =
      0.003), compared to those without DPN. On stepwise multiple regression, DPN
      status, FTSTS, body sway velocity, BMI, diabetes duration, pain, and gender
      explained 38% of HRQoL variance. Addition of ABC score into the model explained
      45% of variance. Results from structural equation modelling showed that DPN had
      direct effects on HRQoL and indirect effects through FTSTS, body sway velocity,
      and ABC score, with chi 2 = 8.075 (p = 0.044), root mean square error of
      approximation = 0.103 (lower bound 0.015, upper bound 0.191), Comparative Fit
      Index = 0.966, Tucker-Lewis Index = 0.887, and Standardized Root Mean Square
      Residual = 0.053. CONCLUSIONS: Patients with DPN have worse HRQoL compared to
      patients without DPN, partly mediated by functional status parameters. Effective
      interventions targeting functional status may be beneficial in improving HRQoL in
      these patients.

PMID- 29185055
TI  - BioGlue(r) induced granuloma causing symptomatic spinal cord compression: a late
      complication.
AB  - BioGlue(r) is an inert, bioadhesive surgical substance commonly used in spinal
      surgery to aid dural closure. The authors describe two cases in which the use of
      BioGlue(r) caused a local reaction culminating in the formation of a granuloma
      that caused cord compression several years after surgery in one case in which a
      second operation was required to relieve cord compression and remove the foreign
      material. In the other case spontaneous resolution occurred. To our knowledge
      these are the first reports of delayed spinal cord compression secondary to
      BioGlue(r)-induced granuloma. We recommend judicious use of this substance.

PMID- 29185056
TI  - Intramedullary holocord abscess secondary to infected dermoid cyst.
AB  - In the literature, less than ten cases of holocord intramedullary abscess in
      children have been described. A 15-month-old girl presented with flaccid
      paraplegia and dermal sinus in the sacral region. MRI highlighted an infected
      lumbar dermoid cyst. The child underwent surgery to remove the cyst and purulent
      collection. Five days after surgery, she developed upper limbs paresis. An MRI
      showed a holocord abscess. A catheter was inserted through a cervical myelotomy
      into the abscess for drainage with a good postoperative recovery. A rapid
      management, even for extended or recurrent intramedullary abscess, can prevent
      potential severe neurological dysfunctions.

PMID- 29185057
TI  - Implications of a paediatrician-psychologist tandem for sickle cell disease care
      and impact on cognitive functioning.
AB  - : Sickle cell disease (SCD), a life-threatening chronic disease, necessitates a
      paediatric treatment plan that considers the influence of psychological, family
      and intercultural factors. At the Louis-Mourier Hospital (APHP) in Colombes,
      France, we introduced an original paediatric-psychological partnership where a
      clinical psychologist accompanies the paediatrician at programmed consultations.
      We evaluated children and their parents treated in Colombes and in two other
      paediatric units using standardized culture-free tools and clinical interviews to
      evaluate the psychological repercussions of SCD. We first present a global view
      of the different ways that SCD affects both children and their families. We then
      discuss findings from a study evaluating the overall efficacy of an integrated
      psycho-medical treatment model as compared to the usual medical care model.
      Children in the integrated care model improved their cognitive functioning
      assessed using the Rey-Osterrieth complex figure test compared to treatment as
      usual. CONCLUSION: Findings suggest that the concept of a "partnership practice"
      can improve children's ability to grapple with SCD and is a promising approach
      for long-term care of SCD. What is Known: * Painful crises of sickle cell disease
      are unpredictable and appear in early childhood * Stress as well as the complex
      psychological and intercultural issues associated with SCD may aggravate the
      children's symptoms * Standard pediatric care and research deal primarily with
      medical issues What is New: * Evidence-based research examining the psychological
      repercussions of SCD in pediatric treatment as well as the parental distress *
      First study using standardized culture-free tools * Cognitive functioning
      improves under an innovative "partnership" model.

PMID- 29185058
TI  - Content-based image retrieval for Lung Nodule Classification Using Texture
      Features and Learned Distance Metric.
AB  - Similarity measurement of lung nodules is a critical component in content-based
      image retrieval (CBIR), which can be useful in differentiating between benign and
      malignant lung nodules on computer tomography (CT). This paper proposes a new two
      step CBIR scheme (TSCBIR) for computer-aided diagnosis of lung nodules. Two
      similarity metrics, semantic relevance and visual similarity, are introduced to
      measure the similarity of different nodules. The first step is to search for K
      most similar reference ROIs for each queried ROI with the semantic relevance
      metric. The second step is to weight each retrieved ROI based on its visual
      similarity to the queried ROI. The probability is computed to predict the
      likelihood of the queried ROI depicting a malignant lesion. In order to verify
      the feasibility of the proposed algorithm, a lung nodule dataset including 366
      nodule regions of interest (ROIs) is assembled from LIDC-IDRI lung images on CT
      scans. Three groups of texture features are implemented to represent a nodule
      ROI. Our experimental results on the assembled lung nodule dataset show good
      performance improvement over existing popular classifiers.

PMID- 29185061
TI  - Electronic structures of elements according to ionization energies.
AB  - The electronic structures of elements in the periodic table were analyzed using
      available experimental ionization energies. Two new parameters were defined to
      carry out the study. The first parameter-apparent nuclear charge (ANC)-quantified
      the overall charge of the nucleus and inner electrons observed by an outer
      electron during the ionization process. This parameter was utilized to define a
      second parameter, which presented the shielding ability of an electron against
      the nuclear charge. This second parameter-electron shielding effect (ESE)
      provided an insight into the electronic structure of atoms. This article avoids
      any sort of approximation, interpolation or extrapolation. First experimental
      ionization energies were used to obtain the two aforementioned parameters. The
      second parameter (ESE) was then graphed against the electron number of each
      element, and was used to read the corresponding electronic structure. The ESE
      showed spikes/peaks at the end of each electronic shell, providing insight into
      when an electronic shell closes and a new one starts. The electronic structures
      of elements in the periodic table were mapped using this methodology. These
      graphs did not show complete agreement with the previously known "Aufbau" filling
      rule. A new filling rule was suggested based on the present observations.
      Finally, a new way to organize elements in the periodic table is suggested. Two
      earlier topics of effective nuclear charge, and shielding factor were also
      briefly discussed and compared numerically to demonstrate the capability of the
      new approach.

PMID- 29185060
TI  - The CompTox Chemistry Dashboard: a community data resource for environmental
      chemistry.
AB  - Despite an abundance of online databases providing access to chemical data, there
      is increasing demand for high-quality, structure-curated, open data to meet the
      various needs of the environmental sciences and computational toxicology
      communities. The U.S. Environmental Protection Agency's (EPA) web-based CompTox
      Chemistry Dashboard is addressing these needs by integrating diverse types of
      relevant domain data through a cheminformatics layer, built upon a database of
      curated substances linked to chemical structures. These data include
      physicochemical, environmental fate and transport, exposure, usage, in vivo
      toxicity, and in vitro bioassay data, surfaced through an integration hub with
      link-outs to additional EPA data and public domain online resources. Batch
      searching allows for direct chemical identifier (ID) mapping and downloading of
      multiple data streams in several different formats. This facilitates fast access
      to available structure, property, toxicity, and bioassay data for collections of
      chemicals (hundreds to thousands at a time). Advanced search capabilities are
      available to support, for example, non-targeted analysis and identification of
      chemicals using mass spectrometry. The contents of the chemistry database,
      presently containing ~ 760,000 substances, are available as public domain data
      for download. The chemistry content underpinning the Dashboard has been
      aggregated over the past 15 years by both manual and auto-curation techniques
      within EPA's DSSTox project. DSSTox chemical content is subject to strict quality
      controls to enforce consistency among chemical substance-structure identifiers,
      as well as list curation review to ensure accurate linkages of DSSTox substances
      to chemical lists and associated data. The Dashboard, publicly launched in April
      2016, has expanded considerably in content and user traffic over the past year.
      It is continuously evolving with the growth of DSSTox into high-interest or data
      rich domains of interest to EPA, such as chemicals on the Toxic Substances
      Control Act listing, while providing the user community with a flexible and
      dynamic web-based platform for integration, processing, visualization and
      delivery of data and resources. The Dashboard provides support for a broad array
      of research and regulatory programs across the worldwide community of
      toxicologists and environmental scientists.

PMID- 29185059
TI  - Aerobic but not Resistance Exercise Can Induce Inflammatory Pathways via Toll
      Like 2 and 4: a Systematic Review.
AB  - BACKGROUND: Only a few studies have addressed the relationship between toll-like
      receptors 2 and 4 (TLR2 and TLR4) and the production of local and systemic
      cytokines in response to physical exercise, and they have produced conflicting
      results. We aimed to determine whether acute and chronic exercise outcomes are
      associated with changes in TLR2 and TLR4 expression and signaling and if so, the
      mechanisms that connect them. METHODS: PubMed database were consulted. This
      systematic review selected 39 articles, 26 involving humans and 13 based on
      rodents. RESULTS: In acute resistance exercise studies, 75% reported a decrease
      in TLR4 or TLR2 expression and 25% did not find differences. For chronic
      resistance exercise studies, 67% reported a reduction of expression and 33% did
      not find differences. Studies of both types reported reductions in pro
      inflammatory cytokines. In acute aerobic exercise studies, 40% revealed a decline
      in the expression of the receptors, 7% reported no significant difference, 40%
      showed an increase, and 13% did not evaluate their expression. Fifty-eight
      percent of studies of chronic aerobic exercise revealed a reduction in
      expression, 17% did not find a difference, and 25% reported increases; they also
      suggested that the expression of the receptors might be correlated with that of
      inflammatory cytokines. In studies on combined exercise, 50% reported a decline
      in receptors expression and 50% did not find a difference. CONCLUSIONS: The
      majority of the articles (54%) link different types of exercise to a decline in
      TLR4 and TLR2 expression. However, aerobic exercise may induce inflammations
      through its influence on these receptor pathways. Higher levels of inflammation
      were seen in acute sessions (40%) than regular sessions (25%).

PMID- 29185063
TI  - Laparoscopic low anterior resection combined with "dog-ear" invagination
      anastomosis for mid- and distal rectal cancer.

PMID- 29185064
TI  - The effect of hair removal after surgery for sacrococcygeal pilonidal sinus
      disease: a systematic review of the literature.
AB  - BACKGROUND: It has been suggested that removal of body hair in the sacrococcygeal
      area prevents recurrence after surgery for sacrococcygeal pilonidal sinus disease
      (SPSD). The aim of this study was to review the literature regarding the effect
      of hair depilation on the recurrence rate in patients surgically treated for
      SPSD. METHODS: A systematic search was performed in PubMed, EMBASE, and The
      Cochrane Library by using synonyms for SPSD. Title, abstract, and full text were
      screened by two independent reviewers. Data were systematically collected from
      all included studies by using a standardized data extraction form. RESULTS: The
      search and selection yielded 14 studies, involving 963 patients. The study design
      of the included studies was: retrospective cohort (n = 7), prospective cohort (n
      = 3), randomized controlled trial (n = 2), and case-control (n = 2).The mean
      length of follow-up was 37.0 (standard error of the mean: 35.0) months. The
      recurrence rate was 9.3% (34 out of 366 patients) in patients who had laser hair
      removal, 23.4% (36 out of 154 patients) in those who had razor shaving/cream
      depilation, and 19.7% (85 out of 431 patients) in those who had no hair removal
      after surgery for SPSD. CONCLUSIONS: This systematic review showed a lower
      recurrence rate after laser hair removal compared to no hair removal and
      razor/cream depilation. Due to the small sample size and limited methodological
      quality of the included studies, a high-quality randomized controlled trial is
      required.

PMID- 29185062
TI  - Early Recognition and Treatment Heralds Optimal Outcomes: the Benefits of
      Combined Rheumatology-Dermatology Clinics and Integrative Care of Psoriasis and
      Psoriatic Arthritis Patients.
AB  - PURPOSE OF REVIEW: Diagnosis and treatment of psoriatic arthritis (PsA) can be
      challenging and require a multidisciplinary approach. This review provides an
      overview of combined dermatology-rheumatology clinics. RECENT FINDINGS: Combined
      dermatology-rheumatology clinics have emerged to optimize integrated care for
      patients with psoriasis and PsA. There are over 20 such clinics across the USA.
      These clinics facilitate multidisciplinary care for patients with psoriasis and
      PsA and have been found to improve outcomes and enhance both patient and
      physician satisfaction and knowledge. Challenges presented by these clinics
      include appropriate scheduling for both dermatologists and rheumatologists and
      proving the benefits of the clinics to obtain institutional support. Combined
      dermatology-rheumatology clinics are a novel model of care for patients with
      psoriasis and PsA. They improve outcomes, patient and physician satisfaction, and
      efficiency. As more of these clinics are established, we must further understand
      their impact on outcomes and care processes.

PMID- 29185065
TI  - Consensus queries in ligand-based virtual screening experiments.
AB  - BACKGROUND: In ligand-based virtual screening experiments, a known active ligand
      is used in similarity searches to find putative active compounds for the same
      protein target. When there are several known active molecules, screening using
      all of them is more powerful than screening using a single ligand. A consensus
      query can be created by either screening serially with different ligands before
      merging the obtained similarity scores, or by combining the molecular descriptors
      (i.e. chemical fingerprints) of those ligands. RESULTS: We report on the
      discriminative power and speed of several consensus methods, on two datasets only
      made of experimentally verified molecules. The two datasets contain a total of 19
      protein targets, 3776 known active and ~ 2 * 106 inactive molecules. Three
      chemical fingerprints are investigated: MACCS 166 bits, ECFP4 2048 bits and an
      unfolded version of MOLPRINT2D. Four different consensus policies and five
      consensus sizes were benchmarked. CONCLUSIONS: The best consensus method is to
      rank candidate molecules using the maximum score obtained by each candidate
      molecule versus all known actives. When the number of actives used is small, the
      same screening performance can be approached by a consensus fingerprint. However,
      if the computational exploration of the chemical space is limited by speed (i.e.
      throughput), a consensus fingerprint allows to outperform this consensus of
      scores.

PMID- 29185066
TI  - Electronic structure and bonding of the dinuclear metal M2(CO)10 decacarbonyls:
      applications of natural orbitals for chemical valence.
AB  - The nature of the chemical metal-metal bond in M2(CO)10 (M = Mn, Re, Tc)
      dinuclear decacarbonyls complexes was investigated for the first time using the
      natural orbital chemical valence (NOCV) approach combined with the extended
      transition state (ETS) for energy decomposition analysis (EDA). The optimized
      geometries carried out at different levels of theory BP86, BLYP, BLYPD and BP86D,
      showed that the latter method, i.e., BP86D, led to the best agreement with X-ray
      experimental measurements. The BP86D/TZP results revealed that the computed
      covalent contribution to the metal-metal bond are 60.5%, 54.1% and 52.0% for Mn
      Mn, Re-Re and Tc-Tc, respectively. The computed total interaction energies
      resulting from attractive terms (DeltaE orb and DeltaE eles), correspond well to
      experimental predictions, based on bond lengths and energy interaction analysis
      for the studied complexes.

PMID- 29185068
TI  - Armed for destruction: formation, function and trafficking of neutrophil
      granules.
AB  - Neutrophils respond nearly instantly to infection, rapidly deploying a potent
      enzymatic and chemical arsenal immediately upon entering an infected site. This
      capacity for rapid and potent responses is endowed by stores of antimicrobial
      proteins contained in readily mobilizable granules. These granules contain the
      proteins necessary to mediate the recruitment, chemotaxis, antimicrobial function
      and NET formation of neutrophils. Four granule types exist, and are sequentially
      deployed as neutrophils enter infected sites. Secretory vesicles are released
      first, enabling recruitment of neutrophils out of the blood. Next, specific and
      gelatinase granules are released to enable neutrophil migration and begin the
      formation of an antimicrobial environment. Finally, azurophilic granules release
      potent antimicrobial proteins at the site of infection and into phagosomes. The
      step-wise mobilization of these granules is regulated by calcium signaling, while
      specific trafficking regulators and membrane fusion complexes ensure the delivery
      of granules to the correct subcellular site. In this review, we describe
      neutrophil granules from their formation through to their deployment at the site
      of infection, focusing on recent developments in our understanding of the
      signaling pathways and vesicular trafficking mechanisms which mediate neutrophil
      degranulation.

PMID- 29185067
TI  - Phantom validation of quantitative Y-90 PET/CT-based dosimetry in liver
      radioembolization.
AB  - BACKGROUND: PET/CT has recently been shown to be a viable alternative to
      traditional post-infusion imaging methods providing good quality images of 90Y
      laden microspheres after selective internal radiation therapy (SIRT). In the
      present paper, first we assessed the quantitative accuracy of 90Y-PET using an
      anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical
      homemade lesion located into the hepatic compartment. Then, we explored the
      accuracy of different computational approaches on dose calculation, including (I)
      direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution
      using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo
      technique (MCNP) considering a uniform activity distribution, and (V) MIRD
      (Medical Internal Radiation Dose) analytical approach. Finally, calculated
      absorbed doses were compared with those obtained performing measurements with
      LiF:Mg,Cu,P TLD chips in a liquid environment. RESULTS: Our results indicate that
      despite 90Y-PET being likely to provide high-resolution images, the 90Y low
      branch ratio, along with other image-degrading factors, may produce non-uniform
      activity maps, even in the presence of uniform activity. A systematic
      underestimation of the recovered activity, both for the tumor insert and for the
      liver background, was found. This is particularly true if no partial volume
      correction is applied through recovery coefficients. All dose algorithms
      performed well, the worst case scenario providing an agreement between absorbed
      dose evaluations within 20%. Average absorbed doses determined with the local
      deposition method are in excellent agreement with those obtained using the MIRD
      and the kernel-convolution dose calculation approach. Finally, absorbed dose
      assessed with MC codes are in good agreement with those obtained using TLD in
      liquid solution, thus confirming the soundness of both calculation approaches.
      This is especially true for Raydose, which provided an absorbed dose value within
      3% of the measured dose, well within the stated uncertainties. CONCLUSIONS:
      Patient-specific dosimetry is possible even in a scenario with low true
      coincidences and high random fraction, as in 90Y-PET imaging, granted that
      accurate absolute PET calibration is performed and acquisition times are
      sufficiently long. Despite Monte Carlo calculations seeming to outperform all
      dose estimation algorithms, our data provide a strong argument for encouraging
      the use of the local deposition algorithm for routine 90Y dosimetry based on
      PET/CT imaging, due to its simplicity of implementation.

PMID- 29185069
TI  - Connexin 43 and ATP-sensitive potassium channels crosstalk: a missing link in
      hypoxia/ischemia stress.
AB  - Connexin 43 (Cx43) is a gap junction protein expressed in various tissues and
      organs of vertebrates. Besides functioning as a gap junction, Cx43 also regulates
      diverse cellular processes like cell growth and differentiation, cell migration,
      cell survival, etc. Cx43 is critical for normal cardiac functioning and is
      therefore abundantly expressed in cardiomyocytes. On the other hand, ATP
      sensitive potassium (KATP) channels are metabolic sensors converting metabolic
      changes into electrical activity. These channels are important in maintaining the
      neurotransmitter release, smooth muscle relaxation, cardiac action potential
      repolarization, normal physiology of cellular repolarization, insulin secretion
      and immune function. Cx43 and KATP channels are part of the same signaling
      pathway, regulating cell survival during stress conditions and ischemia/hypoxia
      preconditioning. However, the underlying molecular mechanism for their combined
      role in ischemia/hypoxia preconditioning is largely unknown. The current review
      focuses on understanding the molecular mechanism responsible for the coordinated
      role of Cx43 and KATP channel protein in protecting cardiomyocytes against
      ischemia/hypoxia stress.

PMID- 29185071
TI  - Review: adult neurogenesis contributes to hippocampal plasticity.
AB  - Adult hippocampal neurogenesis is the process by which new functional neurons are
      added to the adult dentate gyrus of the hippocampus. Animal studies have shown
      that the degree of adult hippocampal neurogenesis is regulated by local
      environmental cues as well as neural network activities. Furthermore,
      accumulating evidence has suggested that adult hippocampal neurogenesis plays
      prominent roles in hippocampus-dependent brain functions. In this review, we
      summarize the mechanisms underlying the regulation of adult hippocampal
      neurogenesis at various developmental stages and propose how adult-born neurons
      contribute to structural and functional hippocampal plasticity.

PMID- 29185070
TI  - Single-cell analysis of diversity in human stem cell-derived neurons.
AB  - Neural stem and progenitor cells produce one of the most remarkable organs in
      nature, the human brain. Among neural stem cell progeny, post-mitotic neurons are
      likewise remarkably diverse. Single-cell transcriptomic approaches are now
      cataloging a long-sought-after molecular taxonomy of neuronal diversity in the
      brain. Contemporary single-cell omic classifications of neuronal diversity build
      from electrophysiological approaches that for decades have measured and cataloged
      diverse biophysical properties of single neurons. With the widespread application
      of human pluripotent stem cell-based models of neurogenesis to investigate
      disease pathology and to develop new drugs, a high-resolution understanding of
      neuronal diversity in vivo is essential to benchmark the state of in vitro models
      of human neurological disease.

PMID- 29185072
TI  - In vivo models of alpha-synuclein transmission and propagation.
AB  - The abnormal accumulation of alpha-synuclein aggregates in neurons, nerve fibers,
      or glial cells is the hallmark of a group of neurodegenerative diseases known
      collectively as alpha-synucleinopathies. Clinical, neuropathological, and
      experimental evidence strongly suggests that alpha-synuclein plays a role not
      only as a trigger of pathological processes at disease inception, but also as a
      mediator of pathological spreading during disease progression. Specific
      properties of alpha-synuclein, such as its ability to pass from one neuron to
      another, its tendency to aggregate, and its potential to generate self
      propagating species, have been described and elucidated in animal models and may
      contribute to the relentless exacerbation of Parkinson's disease pathology in
      patients. Animal models used for studying alpha-synuclein accumulation,
      aggregation, and propagation are mostly based on three approaches: (1) intra
      parenchymal inoculations of exogenous alpha-synuclein (e.g., synthetic alpha
      synuclein fibrils), (2) transgenic mice, and (3) animals (mice or rats) in which
      alpha-synuclein overexpression is induced by viral vector injections. Whereas
      pathological alpha-synuclein changes are consistently observed in these models,
      important differences are also found. In particular, pronounced pathology in
      transgenic mice and viral vector-injected animals does not appear to involve self
      propagating alpha-synuclein species. A critical discussion of these models
      reveals their strengths and limitations and provides the basis for
      recommendations concerning their use for future investigations.

PMID- 29185074
TI  - Evaluating the longevity of surgically extracted Xenopus laevis oocytes for the
      study of nematode ligand-gated ion channels.
AB  - Xenopus laevis oocytes have been extensively used as a heterologous expression
      system for the study of ion channels. While used successfully worldwide as tool
      for expressing and characterizing ion channels from a wide range of species, the
      limited longevity of oocytes once removed from the animal can pose significant
      challenges. In this study, we evaluate a simple and useful method that extends
      the longevity of Xenopus oocytes after removal from the animal and quantitatively
      assessed the reliability of the electrophysiological date obtained. The receptor
      used for this study was the UNC-49 receptor originally isolated from the sheep
      parasite, Haemonchus contortus. Overall, we found that immediate storage of the
      ovary in supplemented ND96 storage buffer at 4  degrees C could extend their use
      for up to 17 days with almost 80% providing reliable electrophysiological data.
      This means that a single extraction can provide at least 3 weeks of experiments.
      In addition, we examined 24-day-old oocytes (week 4) extracted from a single frog
      and also obtained reliable data using the same approach. However, 50% of these
      oocytes were usable for full dose-response experiments. Overall, we did find that
      this method has the potential to significantly extend the use of single oocyte
      extractions for two-electrode voltage clamp electrophysiology.

PMID- 29185073
TI  - Computational systems biology approaches for Parkinson's disease.
AB  - Parkinson's disease (PD) is a prime example of a complex and heterogeneous
      disorder, characterized by multifaceted and varied motor- and non-motor symptoms
      and different possible interplays of genetic and environmental risk factors.
      While investigations of individual PD-causing mutations and risk factors in
      isolation are providing important insights to improve our understanding of the
      molecular mechanisms behind PD, there is a growing consensus that a more complete
      understanding of these mechanisms will require an integrative modeling of
      multifactorial disease-associated perturbations in molecular networks.
      Identifying and interpreting the combinatorial effects of multiple PD-associated
      molecular changes may pave the way towards an earlier and reliable diagnosis and
      more effective therapeutic interventions. This review provides an overview of
      computational systems biology approaches developed in recent years to study
      multifactorial molecular alterations in complex disorders, with a focus on PD
      research applications. Strengths and weaknesses of different cellular pathway and
      network analyses, and multivariate machine learning techniques for investigating
      PD-related omics data are discussed, and strategies proposed to exploit the
      synergies of multiple biological knowledge and data sources. A final outlook
      provides an overview of specific challenges and possible next steps for
      translating systems biology findings in PD to new omics-based diagnostic tools
      and targeted, drug-based therapeutic approaches.

PMID- 29185075
TI  - Techniques for the collection, transportation, and isolation of orchid endophytes
      from afar: a case study from Madagascar.
AB  - BACKGROUND: Tropical orchids need more study with respect to their mycorrhizal
      associations. For researchers in distant countries who aspire to study these
      orchids augmenting their conservation, the great distances involved, coupled with
      limited funds, pose formidable challenges. These challenges are sometimes
      exacerbated by political unrest, delays in securing permits, unexpected
      hardships, and the risk that the biological samples collected (e.g., roots
      harboring mycorrhizal fungi) will not survive long-distance transport. RESULTS:
      We describe a protocol for the collection and transport of root samples from
      Madagascar orchids to labs in the United Kingdom (Kew) and the United States
      (Illinois) where Rhizoctonia-like fungi were subsequently isolated. Three
      separate trips were made spanning 4 years (2012-2015), with emphasis on the
      collection of roots from epiphytic, lithophytic, and terrestrial orchids
      inhabiting the Itremo Massif of the Central Highlands. Collectively, the trips to
      Madagascar resulted in the isolation of all major groups of Rhizoctonia-like
      fungi (Ceratobasidium, Tulasnella, Sebacina) from all three orchid growth forms
      (terrestrials, epiphytes and lithophytes). Sampling of terrestrial and epiphytes
      during the rainy season (January) yielded best results. CONCLUSIONS: Our study
      demonstrates that peloton-forming fungi in root samples can retain viability up
      to 3 weeks after collection.

PMID- 29185076
TI  - Correction to: Evidence-based treatment of neurogenic orthostatic hypotension and
      related symptoms.
AB  - Unfortunately, Author has now noticed two mistakes in Fig. 1. Author has written
      "peripher" instead of "peripheral" and "Secundary" instead of "Secondary".

PMID- 29185077
TI  - Premonitory Urge for Tics Scale (PUTS): replication and extension of psychometric
      properties in youth with chronic tic disorders (CTDs).
AB  - Individuals with chronic tic disorders (CTDs) frequently describe aversive
      subjective sensory sensations that precede their tics. The first aim of the
      present study was to explore the psychometric properties of a standardized self
      report measure to assess premonitory urges in CTDs, The Premonitory Urge for Tics
      Scale (PUTS), by replicating the analyses of Woods et al. (J Dev Behav Pediatr
      26:397-403, 2005) using a sample twice the size of theirs. The second aim was to
      conduct an exploratory factor analysis of the PUTS. Eighty-four youth with CTDs,
      recruited from a pediatric OCD and tic specialty clinic, completed the PUTS while
      their caregivers completed The Parent Tic Questionnaire (PTQ) and a demographic
      measure. Consistent with (Woods et al. J Dev Behav Pediatr 26:397-403, 2005), the
      PUTS was found to be internally consistent (alpha = 0.82) and significantly
      correlated with overall tic severity as measured by the PTQ (r = 0.24, p < 0.05)
      as well as the PTQ number (r = 0.34, p < 0.01) and intensity (r = 0.24, p < 0.05)
      subscales. A factor-analysis of the PUTS revealed a two-factor solution with one
      factor capturing the quality of premonitory sensations while the other factor
      assessed the overall intensity of the urges. These results support the use of the
      PUTS in reliably measuring premonitory urges, particularly in children over the
      age of 10 years. Additionally, these findings highlight that urges are uniformly
      reported across gender and age and are more closely associated with number of
      tics than the frequency or intensity of tics.

PMID- 29185078
TI  - Evaluation of autonomic functions of patients with multiple system atrophy and
      Parkinson's disease by head-up tilt test.
AB  - The aim of this study was to evaluate the autonomic neural function in
      Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test
      and spectral analysis of cardiovascular parameters. This study included 15
      patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects.
      High frequency power of the RR interval (RR-HF), the ratio of low frequency power
      of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to
      evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic
      functions, respectively. Both patients with PD and MSA showed orthostatic
      hypotension and lower parasympathetic function (RR-HF) at tilt position as
      compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was
      significantly high in patients with PD than MSA at supine position. RR-LF/HF
      tended to increase in MSA and HC, but decreased in PD by tilting. Consequently,
      the change of the ratio due to tilting (DeltaRR-LF/HF) was significantly lower in
      patients with PD than in HC subjects. Further analysis showed that compared to
      mild stage of PD, RR-LF/HF at the supine position was significantly higher in
      advanced stage. By tilting, it was increased in mild stage and decreased in the
      advanced stage of PD, causing DeltaRR-LF/HF to decrease significantly in the
      advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular
      parameters is useful to identify sympathetic and parasympathetic disorders in MSA
      and PD. High cardiac sympathetic function at the supine position, and its
      reduction by tilting might be a characteristic feature of PD, especially in the
      advanced stage.

PMID- 29185079
TI  - Gender Moderates the Association of Depressive Symptoms to Sexual Risk Behavior
      Among HIV-Positive African-American Outpatients.
AB  - Previous research has reported an association between depressive symptoms and
      sexual risk behavior. The purpose of this study was to explore whether gender
      moderates this association in a sample of HIV-positive African-Americans.
      Participants (N = 93) self-reported depressive symptoms (Center for
      Epidemiological Studies-Depression Scale; CES-D), and sexual risk behavior for
      the past 4 months. Analyses revealed that the depressive symptoms-by-gender
      interaction was associated with condomless sex and substance use proximal to sex.
      When analyses were stratified by gender, depressive symptoms were associated with
      condomless sex and frequency of substance use only for women. We conclude that
      depressive symptoms may be a more powerful sexual risk factor among women
      relative to men.

PMID- 29185080
TI  - Manganese and cobalt recovery by surface display of metal binding peptide on
      various loops of OmpC in Escherichia coli.
AB  - In a cell-surface display (CSD) system, successful display of a protein or
      peptide is highly dependent on the anchoring motif and the position of the
      display in that anchoring motif. In this study, a recombinant bacterial CSD
      system for manganese (Mn) and cobalt (Co) recovery was developed by employing
      OmpC as an anchoring motif on three different external loops. A portion of Cap43
      protein (TRSRSHTSEG)3 was employed as a manganese and cobalt binding peptide
      (MCBP), which was fused with OmpC at three different external loops. The fusions
      were made at the loop 2 [fusion protein-2 (FP2)], loop 6 (FP6), and loop 8 (FP8)
      of OmpC, respectively. The efficacy of the three recombinant strains in the
      recovery of Mn and Co was evaluated by varying the concentration of the
      respective metal. Molecular modeling studies showed that the short trimeric
      repeats of peptide probably form a secondary structure with OmpC, thereby giving
      rise to a difference in metal recovery among the three recombinant strains. Among
      the three recombinant strains, FP6 showed increased metal recovery with both Mn
      and Co, at 1235.14 (1 mM) and 379.68 (0.2 mM) umol/g dry cell weight (DCW),
      respectively.

PMID- 29185081
TI  - Effect of temperature on diapause termination and post-diapause development in
      Eotetranychus smithi (Acari: Tetranychidae).
AB  - Previous studies on the spider mite Eotetranychus smithi Pritchard & Baker have
      shown that diapause in eggs is induced by low temperature alone and that females
      developed at <= 17.5  degrees C laid diapause eggs, regardless of the
      photoperiod. In this study, diapause eggs were kept at 5  degrees C and a
      photoperiod of 16L:8D for 0-120 days and then maintained at 25  degrees C to know
      the effect of chilling on diapause termination. Diapause eggs mostly hatched when
      they were maintained at 25  degrees C after chilling for 30-90 days at 5  degrees
      C, which suggests that diapause termination is favored by low temperatures. To
      clarify the hatching conditions after diapause termination, diapause eggs kept at
      5  degrees C for 45 days were subsequently maintained at various constant
      temperatures (from 15 to 25  degrees C) under a long-day photoperiod (16L:8D).
      The hatchability at all temperatures tested was high (> 90%) and did not
      significantly differ among the high temperatures. Duration of embryonic
      development was shorter with increasing warming temperature after chilling. The
      lower thermal threshold (t) and thermal constant (k) for post-diapause egg
      development were 10.5  degrees C and 76.9 degree-days, respectively. Females,
      which developed from diapause eggs that were chilled at 5  degrees C for 45 days
      and then maintained at 15  degrees C, laid only non-diapause eggs, which
      indicates that they were prevented from re-entering diapause even under diapause
      inducing conditions (15  degrees C). Thus, temperature is the main factor to
      control diapause termination and post-diapause development, which has also been
      found for other spider mites that enter diapause at the egg stage.

PMID- 29185082
TI  - Multi-energy spectral CT: adding value in emergency body imaging.
AB  - Most vendors offer scanners capable of dual- or multi-energy computed tomography
      (CT) imaging. Advantages of multi-energy CT scanning include superior tissue
      characterization, detection of subtle iodine uptake differences, and
      opportunities to reduce contrast dose. However, utilization of this technology in
      the emergency department (ED) remains low. The purpose of this pictorial essay is
      to illustrate the value of multi-energy CT scanning in emergency body imaging.

PMID- 29185083
TI  - Linear ubiquitin chain induces apoptosis and inhibits tumor growth.
AB  - Ubiquitination of proliferating cell nuclear antigen (PCNA) plays an important
      role in DNA damage response. Ectopic expression of PCNA fused at either terminus
      with ubiquitin (Ub) lacking two C-terminal glycine residues induces translesion
      DNA synthesis which resembles synthesis mediated by PCNA monoubiquitination. PCNA
      fused with Ub containing the C-terminal Gly residues at the C-terminus can be
      further polyubiquitinated in a Gly-dependent manner, which inhibits cell
      proliferation and induces ATR-dependent replication checkpoint. In this study, we
      surprisingly found that PCNA fused to a head-to-tail linear Ub chain induces
      apoptosis in a Ub chain length-dependent manner. Further investigation revealed
      that the apoptotic effect is actually induced by the linear Ub chain
      independently from PCNA, as the Ub chain fused to GFP or an epitope tag still
      efficiently induces apoptosis. It is revealed that the artificial linear Ub chain
      differs from endogenously encoded linear Ub chains in that its Ubs contain a Ub
      G76S substitution, making the Ub chain resistant to cleavage by deubiquitination
      enzymes. We demonstrated in this study that ectopic expression of the artificial
      Ub chain alone in cultured human cancer cells is sufficient to inhibit tumor
      growth in a xenograft mouse model, making the linear Ub chain a putative anti
      cancer agent.

PMID- 29185084
TI  - A triazole-conjugated benzoxazone induces reactive oxygen species and promotes
      autophagic apoptosis in human lung cancer cells.
AB  - Numerous approaches suggested that compounds with conjugated triazole moieties or
      benzoxazone pharmacores are effective to antagonize proliferation of human
      tumors. The current study reported that a synthetic triazole-conjugated
      benzoxazone, 4-((5-benzyl-1H-1,2,3-triazol-3-yl)-methyl)-7-methoxy-2H
      benzo[b][1,4]-oxazin-3(4H)-one (BTO), inhibited growth rates of human non-small
      cell lung cancer cells. The cytotoxicity can be enhanced with increasing drug
      concentrations. More evidence supported that the induced reactive oxygen species
      lead to ultimate apoptotic cell death by recruiting autophagy. The mechanistic
      pathway as elucidated involved tumor suppressor p53 activation and LC3-1
      conversion followed by PARP and procaspase-3 cleavage. Autophagy inhibition
      reverted apoptotic death and restored cell viabilities. BTO suppressed the
      development of A549 cell xenograft tumors by activating autophagy and apoptosis
      simultaneously. As an efficient tumor growth inhibitor with relatively small
      molecular weight, BTO is a viable addition to the existing list of lung cancer
      treatment.

PMID- 29185085
TI  - Addressing comorbidities in psoriatic disease.
AB  - Psoriasis and PsA are associated with comorbidities including cardiovascular
      disease, obesity, metabolic syndrome and depression. The purpose of this study
      was to examine if patients recognize that they are being monitored for
      comorbidities associated with their condition, and to determine which physicians
      are managing these comorbidities. Patients with psoriasis without arthritis (PsC)
      and patients with PsA were recruited from the University of Toronto Psoriasis
      Cohort and Psoriatic Arthritis Clinic, respectively. A comorbidity questionnaire
      was developed through a literature review and patients completed the
      questionnaire at clinic visits or over the telephone. PsA patient responses were
      compared with information recorded by physicians at clinic visits. A total of 268
      patients (103 PsC and 164 PsA) were included. Patients indicated having their
      blood pressure (96.3%), weight (94.4%), blood sugar (75%) and cholesterol (79.5%)
      levels checked, with PsA patients indicating being checked more frequently than
      PsC patients. PsA patients were most uncertain about whether their blood sugar
      and cholesterol levels were checked by physicians. The highest correlation
      between patient responses and physician records occurred for medications for
      diabetes, depression and hypercholesterolemia. Patients indicated their family
      physician were most responsible in monitoring the comorbidities. Overall,
      patients documented being moderately well screened for most comorbidities and
      were most unsure about having their blood sugar and cholesterol levels monitored.
      Patient education and records should be improved at clinic visits, as there are
      discrepancies between patient responses and physician records regarding the
      presence and treatment of comorbidities.

PMID- 29185086
TI  - Interstitial lung disease in South Africans with systemic sclerosis.
AB  - To investigate the frequency, severity and predictors of interstitial lung
      disease (ILD) in a cohort of South Africans with systemic sclerosis (SSc).
      Retrospective record review of SSc patients attending a tertiary Connective
      Tissue Diseases Clinic. Patients with ILD, defined by a combination of clinical
      findings, imaging, and lung function tests were compared to patients without ILD
      in terms of demographics, clinical features and autoantibodies. The majority
      (86.8%) of the 151 patients included were of Black ethnicity, 40% had ILD, of
      whom 39% had moderate-severe lung disease. Univariate predictors of ILD included:
      disease duration (OR 1.08, 95% CI 1.01-1.15); cough (OR 2.93, 95% CI 1.37-6.29);
      dyspnoea (OR 2.44, 95% CI 1.23-4.87); bibasal crackles (OR 7.58, 95% CI 3.31
      17.37); diffuse cutaneous SSc (dcSSc) (OR 4.55, 95% CI 2.10-9.86) and a speckled
      anti-nuclear antibody (ANA) pattern (OR 2.47, 95% CI 1.25-4.90). Conversely,
      limited cutaneous disease (OR 0.22, 95% CI 0.09-0.50) and anti-centromere
      antibody (ACA) (OR 0.12, 95% CI 0.02-0.97) were protective. Independent
      predictors of ILD on multivariate analysis were bibasal crackles (OR 9.43, 95% CI
      3.25-27.39), disease duration (OR 1.19, 95% CI 1.09-1.30) and speckled ANA (OR
      2.95, 95% CI 1.22-7.15). Almost all (86.4%) patients received immunosuppressive
      treatment and the leading cause of death was related to ILD itself (44.4%). In
      this cohort of predominantly Black South Africans, SSc ILD was common and carried
      a poor prognosis. ILD occurred mainly, but not exclusively, in patients with
      dcSSc, especially those with a speckled ANA pattern. Conversely, the presence of
      ACA was protective against ILD.

PMID- 29185088
TI  - Fer-ho Anaphora in Catalan: Semantic and Discourse Properties.
AB  - This paper considers the anaphoric status of the pro-form fer-ho (do it) in
      Catalan [This paper contains some ideas included in Busquets (2005)]. I discuss
      some anaphoric properties of fer-ho as DEEP ANAPHORA. I also compare these
      properties to those of other types of anaphora, like VPE and pseudogapping (PG).
      I show that its interpretation is strongly constrained by information and
      discourse structure.

PMID- 29185087
TI  - Assistive devices: an effective strategy in non-pharmacological treatment for
      hand osteoarthritis-randomized clinical trial.
AB  - : This study aims to evaluate the use of assistive devices as a strategy in non
      pharmacological treatment for hand osteoarthritis (HOA). This is a randomized,
      prospective, parallel, assessor-blinded clinical trial, in which patients with a
      diagnosis of HOA were randomly allocated to an intervention group (IG), where
      they received assistive devices for daily life activities, or to a control group
      (CG), where they received a guideline leaflet with information on joint
      protection and disease features. The primary outcomes considered were
      occupational performance, measured by the Canadian Occupational Performance
      Measure (COPM), and hand function was evaluated through the Score for the
      Assessment and Quantification of Chronic Rheumatoid Affections of the Hands
      (SACRAH). The secondary outcomes were pain, measured by the visual analog scale
      (VAS), and quality of life, measured by the World Health Organization Quality of
      Life Instrument, Short Form (WHOQOL-BREF). We compared both outcomes before and
      after interventions and outcomes between groups. Participants from the two groups
      were assessed at the time of inclusion in the study, 30, and 90 days after
      initial evaluation. Out of the 39 patients included, 19 were allocated to the IG
      and 20 to the CG. Only two patients from the CG did not complete the follow-up
      period. The patients' hand function and occupational performance improved after
      intervention (30 days-SACRAH-p < 0.05; COPM-p < 0.05; VAS-p < 0.05). When
      comparing results between the groups, there was a statistical difference in COPM
      (performance-p < 0.001; and satisfaction-p < 0.001), in the first reevaluation
      carried out. The use of assistive devices has proved to be an effective
      alternative in non-pharmacological treatment for HOA. CLINICAL TRIAL
      REGISTRATION: NCT02667145.

PMID- 29185089
TI  - Pharmacoeconomic evaluation of micafungin versus caspofungin as definitive
      therapy for candidaemia and invasive candidiasis (IC) in Turkey.
AB  - Micafungin was shown to be as efficacious as caspofungin in treating patients
      with candidaemia and invasive candidiasis (IC). However, it remains unknown if
      micafungin or caspofungin is a cost-effective definitive therapy for candidaemia
      and IC in Turkey. The present study aimed to determine the economic impact of
      using micafungin versus caspofungin for treatment of candidaemia and IC in the
      Turkish setting. A decision analytic model was constructed and was populated with
      data (i.e. transition probabilities, duration of initial antifungal treatment,
      reasons for treatment failure, percentage of patients who stepped down to oral
      fluconazole, and duration on oral fluconazole) obtained from a published
      randomised clinical trial. Cost inputs were derived from the latest Turkish
      resources while data that were not readily available in the literature were
      estimated by expert panels. One-way sensitivity analyses, threshold analyses,
      scenario analyses and probabilistic sensitivity analyses were conducted.
      Caspofungin (?2693) incurred a lower total cost than micafungin (?4422), with a
      net cost saving of ?1729 per treated patient. Drug acquisition cost was the main
      cost driver for both study arms. The model outcome was robust over wide
      variations (of +/-100.0% from the base case value) for all input parameters
      except for micafungin drug cost and the duration of initial treatment with
      micafungin. Caspofungin appears to be a cost-saving option in treating
      candidaemia and IC from the Turkish hospital perspective.

PMID- 29185090
TI  - Meat consumption and pancreatic cancer risk among men and women in the Cancer
      Prevention Study-II Nutrition Cohort.
AB  - PURPOSE: Prospective cohort studies suggest that red and processed meat
      consumption is associated with increased risk of pancreatic cancer among men, but
      not women. However, evidence is limited, and less evidence exists for other types
      of meat. METHODS: Cox proportional hazards regression was used to estimate
      multivariable-adjusted hazard ratios (HR) for the association of meat
      consumption, by type, with pancreatic cancer risk among 138,266 men and women in
      the Cancer Prevention Study-II Nutrition Cohort. Diet was assessed at baseline in
      1992, and 10 years earlier, at enrollment into the parent CPS-II mortality
      cohort. 1,156 pancreatic cancers were verified through 2013. RESULTS: Red meat,
      processed meat, and fish intake at baseline were not associated with pancreatic
      cancer risk. However, for long-term red and processed meat consumption (highest
      quartiles in 1982 and 1992, vs. lowest quartiles), risk appeared different in men
      [hazard ratio (HR) 1.32, 95% confidence interval (CI) 0.90, 1.95] and women (HR
      0.72, 95% CI 0.47, 1.10, p heterogeneity by sex = 0.05). Poultry consumption in
      1992 was associated with increased pancreatic cancer risk (HR 1.27, 95% CI 1.04,
      1.55, p trend = 0.01, top vs. bottom quintile). CONCLUSIONS: The associations of
      meat consumption with pancreatic cancer risk remain unclear and further research,
      particularly of long-term intake, is warranted.

PMID- 29185091
TI  - Induction of apoptosis in breast cancer cells in vitro by Fas ligand reverse
      signaling.
AB  - PURPOSE: The Fas-antigen is a cell surface receptor that transduces apoptotic
      signals into cells. The purpose of this study was to evaluate FasL expression in
      breast cancer and to elucidate the role of its signaling in different breast
      cancer cell lines. METHODS: T47D and MCF7 cells were used and cultured in
      Dulbecco's modified Eagle's medium. FasL translocation to the membrane was
      achieved by culturing the cells in the presence of human interferon-gamma
      (IFNgamma). Translocation was detected by immunofluorescence. The ability of a
      Fas:Fc fusion protein to trigger apoptosis in these cells was investigated by
      cell death detection ELISA. After incubation with IFNgamma for 4 h and 18 h,
      apoptosis was assessed in response to treatment with Fas:Fc. RESULTS:
      Immunofluorescence revealed that the used cell lines were positive for FasL which
      was increased and changed to more membrane-bound FasL expression after IFNgamma
      stimulation. After stimulation with 50 IU/ml IFNgamma, Fas:Fc significantly
      increased MCF7 apoptosis (1.39 +/- 0.06-fold, p = 0.0004) after 18 h. After
      stimulation with 100 IU/ml, Fas:Fc significantly increased apoptosis both after 4
      h (1.49 +/- 0.15-fold, p = 0.018) and 18 h (1.30 +/- 0.06-fold, p = 0.013). In
      T47D cells this effect was seen after 4 h of stimulation with 50 IU/ml and
      addition of Fas:Fc (1.6 +/- 0.08-fold, p = 0.03). CONCLUSION: Membrane-bound FasL
      expression could be induced by IFNgamma in a breast cancer cell model. More
      importantly, in the presence of IFNgamma the Fas:Fc fusion protein was able to
      transmit pro-apoptotic signals to T47D and MCF7 cells, significantly inducing
      apoptosis. The current findings support further in vivo studies regarding FasL
      activation as a potential target for therapeutic intervention in breast cancer.

PMID- 29185093
TI  - Sexuality Within Female Same-Gender Couples: Definitions of Sex, Sexual Frequency
      Norms, and Factors Associated with Sexual Satisfaction.
AB  - Despite a growing number of female same-gender (FSG) relationships, couples-based
      research and interventions have focused primarily on mixed-gender couples.
      Consequently, research has applied a heteronormative lens to understanding some
      relationship factors, including sexuality. The current study sought to provide
      descriptive data regarding frequency and conceptualizations of sex across
      partners in FSG relationships, as well as to analyze how relationship factors are
      associated with sexual satisfaction in this population. Participants (N = 206)
      were 103 adult FSG couples who had been together for at least 2 months.
      Individuals provided self-report data on how they conceptualized sex, and actor
      partner models were utilized to assess relationship factors associated with
      sexual satisfaction. Findings indicated that women in FSG relationships hold
      broad definitions of sex, with the majority of behaviors conceptualized as sex,
      including acts that involved partnered genital touching. In dyadic actor-partner
      models, sexual satisfaction was predicted by several factors including sexual
      frequency, emotional intimacy, and sexual intimacy. Unexpectedly, higher desired
      sexual frequency was associated with lower sexual satisfaction; however, this
      finding only emerged after controlling for actual sexual frequency, suggesting
      that discrepancies between desired and actual sex frequency may be important for
      FSG couples. Implications for clinical practice with FSG couples are explored,
      including a strength-based focus on broad conceptualizations of sex within this
      population and targeting relationship factors associated with sexual
      satisfaction.

PMID- 29185092
TI  - Analysis of TSC1 mutation spectrum in mucosal melanoma.
AB  - PURPOSE: Mucosal melanoma is a relatively rare subtype of melanoma for which no
      clearly established therapeutic strategy exists. The genes of the mTOR signalling
      pathway have drawn great attention as key targets for cancer treatment, including
      melanoma. In this study, we aimed to investigate the mutation status of the
      upstream mTOR regulator TSC1 and evaluated its correlation with the
      clinicopathological features of mucosal melanoma. METHODS: We collected 91
      mucosal melanoma samples for detecting TSC1 mutations. All the coding exons of
      TSC1 were amplified by PCR and subjected to Sanger sequencing. Expression level
      of TSC1 encoding protein (hamartin) was detected by immunohistochemistry. The
      activation of mTOR pathway was determined by evaluating the phosphorylation
      status of S6RP and 4E-BP1. RESULTS: The overall mutation frequency of TSC1 was
      found to be 17.6% (16/91 patients). TSC1 mutations were more inclined to occur in
      advanced mucosal melanoma (stages III and IV). In the 16 patients with TSC1
      mutations, 14 different mutations were detected, affecting 11 different exons.
      TSC1 mutations were correlated with upregulation of S6RP phosphorylation but were
      unrelated to 4E-BP1 phosphorylation or hamartin expression. Mucosal melanoma
      patients with TSC1 mutations had a worse outcome than patients without TSC1
      mutations (24.0 versus 34.0 months, P = 0.007). CONCLUSIONS: Our findings suggest
      that TSC1 mutations are frequent in mucosal melanoma. TSC1 mutations can activate
      the mTOR pathway through phospho-S6RP and might be a poor prognostic predictor of
      mucosal melanoma. Our data implicate the potential significance of TSC1 mutations
      for effective and specific drug therapy for mucosal melanoma.

PMID- 29185094
TI  - A Theory-Based Exploration of Condomless Anal Intercourse Intention Among Young
      Men Who Have Sex with Men of Different Sexual Roles in Taiwan.
AB  - In recent years, men who have sex with men (MSM) have accounted for over 80% of
      all new HIV cases in Taiwan. More than 70% of new cases have occurred in those
      aged 15-34 years. Condomless anal intercourse (CAI) has been identified as the
      main route of HIV transmission among MSM. To systematically examine CAI intention
      and associated factors among young MSM in Taiwan, an anonymous online survey
      based on the Theory of Planned Behavior (TPB) was conducted. Data from 694 MSM
      aged 15-39 years were included in the analysis. This study found that, overall,
      all five TPB factors (i.e., attitudes toward positive and negative outcomes
      regarding CAI, perceived support for CAI from important others, and perceived
      behavioral control of CAI under facilitating and constraining conditions) were
      significantly associated with CAI intention. When data were stratified by sexual
      role (i.e., receptive, versatile, and insertive), the associations between TPB
      factors and CAI intention varied. Of the five TPB factors, positive attitudes
      toward positive outcomes regarding CAI were most strongly associated with high
      CAI intention (AOR 5.68 for all young MSM; AOR 3.80-15.93, depending on sexual
      role). Findings from this study could inform the development of theory-driven HIV
      prevention programs as well as future research and practice. These results also
      highlight the importance of tailoring HIV prevention initiatives for young MSM of
      different sexual roles to optimize the program effectiveness.

PMID- 29185096
TI  - [The atrial appendage occluder : A real alternative treatment for stroke
      prevention in atrial fibrillation?]

PMID- 29185095
TI  - Management of hereditary breast and ovarian cancer.
AB  - Hereditary breast and ovarian cancer (HBOC) syndrome represents 5-10% of all
      breast cancers. In Japan, the HBOC syndrome is frequently diagnosed in patients
      with breast cancer. Therefore, a treatment strategy combining a plan for existing
      breast cancer and for reduction of future breast and ovarian cancer risk is
      necessary. Breast cancer risk-reducing management involves three options
      surveillance, chemoprevention, and risk-reducing mastectomy (RRM). RRM can
      prevent >90% of new breast cancers. Ovarian cancer risk management options are
      more limited, and risk-reduction salpingo-oophorectomy is the only option since
      there is no proven effective early detection method available. The local
      recurrence rate following breast-conserving surgery in BRCA1/2 mutation
      associated breast cancer is not significantly higher than that in sporadic breast
      cancer. Furthermore, there is no difference in prognosis between surgical
      methods. Clinicians should inform patients that there are no data on long-term
      monitoring and fully discuss risks of re-developing breast cancer with patients
      when choosing the surgical method. In HBOC, BRCA1/2 mutations lead to failure of
      double-strand DNA break repair, with poly ADP-ribose polymerase (PARP) playing an
      important role in single-strand DNA nick repair. Use of PARP inhibitors in HBOC
      prevents DNA repair (synthetic lethality) leading to cell death. This review
      summarizes management of the HBOC syndrome based on recent evidence.

PMID- 29185097
TI  - Age and Charlson Score.

PMID- 29185098
TI  - Confusion Over Differences in Registration and Randomization Criteria for the
      LORIS (Low-Risk DCIS) Trial.

PMID- 29185099
TI  - Real-life clinical data for dexamethasone and ranibizumab in the treatment of
      branch or central retinal vein occlusion over a period of six months.
AB  - PURPOSE: To evaluate the therapeutic outcome for dexamethasone implant (DEX) or
      intravitreal ranibizumab (IVR) injections over 6 months in patients with macular
      edema due to branch or central retinal vein occlusion (BRVO, CRVO), in a real
      life setting. METHODS: A total of 107 patients with BRVO or CRVO were included
      into this retrospective single-center observational study. Patients were treated
      with monotherapy consisting of DEX or three monthly IVR injections following a
      pro re nata regimen (PRN). Best-corrected visual acuity (BCVA), central retinal
      thickness (CRT) and intraocular pressure (IOP) were compared between the two
      therapy groups after 1, 3 and 6 months. RESULTS: BRVO patients treated with DEX
      achieved a statistically significant gain in BCVA measured in logMAR after 1
      month (mean gain, 95% CI: 0.21, 0.08-0.34, p = 0.001), 3 months (0.16, 0.03-0.28,
      p = 0.012) and 6 months (0.19, 0.07-0.32, p = 0.002), whereas patients treated
      with IVR showed a statistically significant BCVA gain in month 3 (mean
      improvement, 95% CI: 0.13, 0.01-0.26, p = 0.039) and month 6 (0.16, 0.03-0.29, p
      = 0.018). BCVA in CRVO patients with DEX worsened slightly at month 6 (mean
      worsening, 95% CI: -0.08, -0.24 to 0.08, p = 0.305), while IVR treated-patients
      achieved a statistically significant BCVA gain at 3 months (mean improvement, 95%
      CI: 0.14, 0.02-0.25, p = 0.021). Both therapies were accompanied by statistically
      significant CRT reductions of 150 to 200 MUm (median). Adverse events reported
      were predictable and limited. CONCLUSIONS: In a clinical setting, comparable
      improvement in BCVA and CRT were observed after DEX and IVR injections for
      treatment of BRVO. CRVO patients showed greater benefit with IVR.

PMID- 29185100
TI  - Spatial distribution of CD115+ and CD11b+ cells and their temporal activation
      during oxygen-induced retinopathy in mice.
AB  - PURPOSE: The model of oxygen-induced retinopathy (OIR) is widely used to analyze
      pathomechanisms in retinal neovascularization. Previous studies have shown that
      macrophages (MP) play a key role in vessel formation in OIR, the influence of
      microglia (MG) having been discussed. The aim of our study was to analyze the
      spatial and temporal distribution and activation of MP/MG expressing CD115 and
      CD11b during the process of neovascularization in OIR. METHODS: We used MacGreen
      mice expressing the green fluorescence protein (GFP) under the promoter for
      CD115. CD115+ cells were investigated in vivo by scanning laser ophthalmoscopy at
      postnatal days (P) 17 and 21 in MacGreen mice with OIR (75% oxygen from P7 to
      P12), and were compared to MacGreen room-air controls. In addition MP/MG were
      examined ex vivo using immunohistochemistry for CD11b+ detection on retinal
      flatmounts at P14, P17, and P21 of wild type mice with OIR. RESULTS: In-vivo
      imaging revealed the highest density of activated MP/MG in tuft areas at P17 of
      MacGreen mice with OIR. Tufts and regions with a high density of CD115+ cells
      were detected close to veins, rather to arteries. In peripheral, fully
      vascularized areas, the distribution of CD115+ cells in MacGreen mice with OIR
      was similar to MacGreen room-air controls. Correspondingly, immunohistochemical
      analyses of retinal flatmounts from wild type mice with OIR induction revealed
      that the number of CD11b+ cells significantly varies between vascular, avascular,
      and tuft areas as well as between the retinal layers. Activated CD11b+ cells were
      almost exclusively found in avascular areas and tufts of wild type mice with OIR
      induction; here, the proportion of activated cells related to the total number of
      CD11b+ cells remained stable over the course of time. CONCLUSIONS: Using two
      different approaches to monitor MP/MG cells, our findings demonstrated that MP/MG
      concentrate within pathologically vascularized areas during OIR. We were able to
      clarify that reactive changes of CD11b+ cell distribution to OIR primarily occur
      in the deep retinal layers. Furthermore, we found the highest proportion of
      activated CD11b+ cells in regions with pathologic neovascularization processes.
      Our findings support previous reports about activated MP/MG guiding
      revascularization in avascular areas and playing a key role in the formation and
      regression of neovascular tufts.

PMID- 29185102
TI  - Systematic Layout Planning of a Radiology Reporting Area to Optimize
      Radiologists' Performance.
AB  - Optimizing radiologists' performance is a major priority for managers of health
      services/systems, since the radiologists' reporting activity imposes a severe
      constraint on radiology productivity. Despite that, methods to optimize
      radiologists' reporting workplace layout are scarce in the literature. This study
      was performed in the Radiology Division (RD) of an 850-bed University-based
      general hospital. The analysis of the reporting workplace layout was carried out
      using the systematic layout planning (SLP) method, in association with cluster
      analysis as a complementary tool in early stages of SLP. Radiologists,
      architects, and hospital managers were the stakeholders consulted for the
      completion of different stages of the layout planning process. A step-by-step
      description of the proposed methodology to plan an RD reporting layout is
      presented. Clusters of radiologists were defined using types of exams reported
      and their frequency of occurrence as clustering variables. Sectors with high
      degree of interaction were placed in proximity in the new RD layout, with
      separation of noisy and quiet areas. Four reporting cells were positioned in the
      quiet area, grouping radiologists by subspecialty, as follows: cluster 1-abdomen;
      cluster 2-musculoskeletal; cluster 3-neurological, vascular and head & neck;
      cluster 4-thoracic and cardiac. The creation of reporting cells has the potential
      to limit unplanned interruptions and enhance the exchange of knowledge and
      information within cells, joining radiologists with the same expertise. That
      should lead to improvements in productivity, allowing managers to more easily
      monitor radiologists' performance.

PMID- 29185103
TI  - Unraveling the Interaction of Aspirin, Ticagrelor, and Rosuvastatin on the
      Progression of Atherosclerosis and Inflammation in Diabetic Mice.
AB  - PURPOSE: We explored the effects of rosuvastatin, aspirin, ticagrelor, and
      clopidogrel, alone or in combinations on the progression of atherosclerosis and
      inflammasome activation in diabetic mice. Statins and ticagrelor increase the
      production of 15-epi-lipoxin A4 via cyclooxygenase-2. Aspirin alone increases 15
      epi-lipoxin A4, but when combined with statins, cyclooxygenase-2 is completely
      blocked. METHODS: ApoE-/-/db+/db+ double-knockout mice received rosuvastatin (5
      mg/kg/day), aspirin (25 mg/kg/day), ticagrelor (300 mg/kg/day), clopidogrel (75
      mg/kg/day), or their combination for 14 weeks. Serum 15-epi-lipoxin A4 levels and
      aortic wall cholesterol content, IL-1beta, IL-6, and TNF-alpha levels, and plaque
      area were assessed. RESULTS: Aspirin, ticagrelor, and rosuvastatin increased 15
      epi-lipoxin A4 levels. The combination of rosuvastatin + ticagrelor provided an
      additive effect. Aspirin attenuated the effect of both ticagrelor and
      rosuvastatin. Aspirin, ticagrelor, and rosuvastatin reduced the area of the
      atherosclerotic plaque. The combination of ticagrelor + rosuvastatin provided
      additive effects. There was a negative interaction when aspirin was combined with
      ticagrelor or rosuvastatin. Aspirin, ticagrelor, and rosuvastatin decreased serum
      IL-1beta and IL-6 levels. There was no interaction between aspirin and ticagrelor
      or aspirin and rosuvastatin, whereas combining rosuvastatin and ticagrelor
      provided an additive effect. Aspirin, ticagrelor, and rosuvastatin all decreased
      TNF-alpha levels. Aspirin attenuated the effect of both ticagrelor and
      rosuvastatin, and there was no additive effect of combining ticagrelor +
      rosuvastatin. CONCLUSIONS: We found an intricate interaction between aspirin,
      ticagrelor, and rosuvastatin, as aspirin reduced both ticagrelor and rosuvastatin
      ability to ameliorate inflammation and atherosclerosis. In contrast, we found
      additive effects when ticagrelor and rosuvastatin were combined.

PMID- 29185101
TI  - Association between traditional clinical high-risk features and gene expression
      profile classification in uveal melanoma.
AB  - PURPOSE: To evaluate the association between traditional clinical high-risk
      features of uveal melanoma patients and gene expression profile (GEP). METHODS:
      This was a retrospective, single-center, case series of patients with uveal
      melanoma. Eighty-three patients met inclusion criteria for the study. Patients
      were examined for the following clinical risk factors: drusen/retinal pigment
      epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan,
      subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and
      largest basal dimensions (LBD). A novel point system was created to grade the
      high-risk clinical features of each tumor. Further analyses were performed to
      assess the degree of association between GEP and each individual risk factor,
      total clinical risk score, vascularity, internal reflectivity, American Joint
      Committee on Cancer (AJCC) tumor stage classification, apical tumor
      height/thickness, and LBD. RESULTS: Of the 83 total patients, 41 were classified
      as GEP class 1A, 17 as class 1B, and 25 as class 2. The presence of orange
      pigment, SRF, low internal reflectivity and vascularity on ultrasound, and apical
      tumor height/thickness >= 2 mm were not statistically significantly associated
      with GEP class. Lack of drusen/RPE changes demonstrated a trend toward
      statistical association with GEP class 2 compared to class 1A/1B. LBD and
      advancing AJCC stage was statistically associated with higher GEP class.
      CONCLUSIONS: In this cohort, AJCC stage classification and LBD were the only
      clinical features statistically associated with GEP class. Clinicians should use
      caution when inferring the growth potential of melanocytic lesions solely from
      traditional funduscopic and ultrasonographic risk factors without GEP data.

PMID- 29185104
TI  - 5alpha-Reductase isozymes and aromatase mRNA levels in plucked hair from young
      women with female pattern hair loss.
AB  - Female pattern hair loss (FPHL) is an important hair disorder, especially when
      young women are affected. However, pharmacological treatments are not successful
      in all women. Androgens, especially dihydrotestosterone (DHT), may play a role in
      FPHL, but many women with this disorder have normal serum androgen levels. It
      therefore appears that hair follicle levels of DHT depend on in situ testosterone
      (T) metabolism. Because T can be converted to DHT or estradiol (E2) by 5alpha
      reductase (5alpha-R) and aromatase, respectively, these enzymes would determine
      DHT and E2 concentrations and their ratio. We propose and apply a low-invasive,
      sensitive and precise method for the absolute quantification of mRNA levels of
      aromatase and 5alpha-R isozymes (type 1, type 2 and type 3) in plucked hair from
      young women with FPHL. Normoandrogenic women with FPHL and controls were studied.
      Plucked hair samples were obtained by trichogram from vertex scalp and mRNA
      levels quantified by real-time RT-PCR. We revealed for the first time the
      presence of 5alpha-R3 mRNA in human hair. Interestingly, one, two, or even three
      5alpha-R isozymes were increased in some women with FPHL but not in others, which
      may explain the lack of response to 5alpha-R inhibitors in some FPHL cases.
      Aromatase mRNA levels were significantly lower in women with FPHL than in
      controls. It may therefore produce a reduction in oestrogen levels and an
      increase in the androgen/oestrogen ratio in hair. The proposed low-invasive
      technique offers a molecular aetiologic diagnosis of FPHL for the selection of
      more appropriate pharmacological treatments with early predicted effectiveness.

PMID- 29185106
TI  - Efficacy of carvedilol versus propranolol versus variceal band ligation for
      primary prevention of variceal bleeding.
AB  - BACKGROUND AND AIMS: Band ligation and propranolol are the current therapies for
      primary prevention of variceal bleeding. Carvedilol is a rising nonselective beta
      blocker used for reducing portal pressure with favorable outcome. The aim of this
      study to assess the efficacy of carvedilol, propranolol, and band ligation for
      primary prevention of variceal bleeding based on the effect of each regimen on
      progression of Child score and portal hypertensive gastropathy after 1 year.
      METHODS: The study included 264 cirrhotic patients with medium/large-sized
      varices who were candidates for primary prophylaxis of variceal bleeding.
      Patients were randomly divided into three groups: group I: band ligation; group
      II: propranolol; group III: carvedilol. RESULTS: Group I showed higher success
      rate of 75 %, followed by group III with 70.2 % and group II with 65.2 %. Risk of
      bleeding was comparable between the three groups, with group II carrying the
      highest rate of complications (34.7 %) followed by group III (14.2 %) and finally
      group I (5.7 %). After 1 year of follow-up, Child score did not improve in any of
      the studied groups, while portal hypertensive gastropathy significantly increased
      in group I but decreased in groups II and III. CONCLUSIONS: Band ligation is the
      best treatment option for primary prevention of variceal bleeding with minimal
      complications. Carvedilol is a good pharmaceutical alternative medicine to
      propranolol with lesser side-effects. Progress of liver disease as represented by
      Child score is not affected by any of the primary variceal prophylactic regimens,
      although medical treatment reduces portal hypertensive gastropathy. Choice of
      treatment depends on patient will, compliance with treatment, and endoscopist
      competence.

PMID- 29185105
TI  - Barriers and facilitators of exercise experienced by cancer survivors: a mixed
      methods systematic review.
AB  - PURPOSE: Exercise has been shown to improve the health and well-being of people
      who have survived cancer. Yet, less than 40% of cancer survivors in Australia
      meet the recommended 150 min of moderate-intensity physical activity per week.
      Our objective was to systematically review the literature regarding barriers,
      facilitators and preferences for exercise for survivors of cancer. METHOD:
      MEDLINE, EMBASE, CINAHL, PsycINFO and Scopus were searched for qualitative and
      quantitative articles addressing barriers, facilitators and preferences for
      exercise in cancer survivors. Quality assessment was performed by two independent
      reviewers using the Mixed Methods Appraisal Tool. Thomas and Harden's method of
      thematic synthesis was used to amalgamate qualitative data while descriptive
      statistics were used to collate quantitative data. RESULTS: Nineteen studies were
      included (9 qualitative and 10 quantitative). Persisting treatment-related side
      effects was the most commonly reported barrier to initiating or maintaining
      exercise, followed by lack of time and fatigue. The most common facilitators of
      exercise were gaining a feeling of control over their health as well as managing
      emotions and mental well-being, while the preferred method of exercise was
      walking. We also identified a lack of useful information provided to survivors
      regarding exercise. CONCLUSION: Treatment-related side effects, lack of time and
      fatigue were key barriers to exercise for survivors of varied cancer types.
      Insufficient patient education may contribute to the belief that exercise is not
      helpful when experiencing side effects of treatment, including fatigue.
      Identifying barriers and facilitators leads to improved support and education
      from health professionals which is required to provide safe and effective
      exercise recommendations for survivors.

PMID- 29185107
TI  - Organization of auditory areas in the superior temporal gyrus of marmoset monkeys
      revealed by real-time optical imaging.
AB  - The prevailing model of the primate auditory cortex proposes a core-belt-parabelt
      structure. The model proposes three auditory areas in the lateral belt region;
      however, it may contain more, as this region has been mapped only at a limited
      spatial resolution. To explore this possibility, we examined the auditory areas
      in the lateral belt region of the marmoset using a high-resolution optical
      imaging technique. Based on responses to pure tones, we identified multiple areas
      in the superior temporal gyrus. The three areas in the core region, the primary
      area (A1), the rostral area (R), and the rostrotemporal area, were readily
      identified from their frequency gradients and positions immediately ventral to
      the lateral sulcus. Three belt areas were identified with frequency gradients and
      relative positions to A1 and R that were in agreement with previous studies: the
      caudolateral area, the middle lateral area, and the anterolateral area (AL).
      Situated between R and AL, however, we identified two additional areas. The first
      was located caudoventral to R with a frequency gradient in the ventrocaudal
      direction, which we named the medial anterolateral (MAL) area. The second was a
      small area with no obvious tonotopy (NT), positioned between the MAL and AL
      areas. Both the MAL and NT areas responded to a wide range of frequencies (at
      least 2-24 kHz). Our results suggest that the belt region caudoventral to R is
      more complex than previously proposed, and we thus call for a refinement of the
      current primate auditory cortex model.

PMID- 29185108
TI  - Neuronal density and proportion of interneurons in the associative, sensorimotor
      and limbic human striatum.
AB  - The striatum (caudate nucleus, putamen and nucleus accumbens) is the main input
      structure of the basal ganglia. It receives cortical projections from the vast
      majority of the cortex, as well as from other subcortical structures such as the
      thalamus and amygdala. Its role in planning, preparation and execution of
      voluntary movements is known to be fine-tuned by the interaction between
      projection neurons and interneurons. Since the 1990s, it has been accepted that
      the proportion of interneurons increases phylogenetically, being about 5% in
      rodents and 26% in humans. However, these data have not been confirmed with
      unbiased techniques, such as stereology. In the present report, we have divided
      the human striatum into functional territories (associative, sensorimotor and
      limbic) and we have quantified the numerical density of all striatal neurons
      (using Nissl staining) in each area. Taking into account our past research on the
      estimation of striatal interneurons, we have calculated the proportion of
      interneurons in each territory. This value was on average 17.1% for the whole
      striatum, although interneurons were more abundant in the associative (21.9%)
      than in the sensorimotor (12.8%) and limbic (11.1%) aspects. Therefore, we
      demonstrate with unbiased stereology that the overall proportion of striatal
      interneurons is slightly lower than that reported in previous studies, and that
      it varies in the functional territories of this structure.

PMID- 29185109
TI  - Higher similarity in beta topography between tasks than subjects.
AB  - We have recently provided evidence for highly idiosyncratic topographic
      distributions of beta oscillations (as well as slow potentials) across
      individuals. More recently, by emphasizing the analysis of similarity instead of
      differences across tasks, we concluded that differences between an attention task
      and quiet resting may be negligible or at least unsystematic across subjects. Due
      to the possibility that individual differences could be due to noise in a wide
      sense or some inherent instability of beta activity, we designed a replication
      study to explicitly test whether pairs of individuals matched for head size and
      shape would still present less similar beta topography than each individual
      between sessions or tasks. We used independent component analysis (ICA) for an
      exhaustive decomposition of beta activity in a visual attention task and in quiet
      resting, recorded by 256-channel EEG in 20 subjects, on two separate days. We
      evaluated whether each ICA component obtained in one task and in one given
      individual could be explained by a linear regression model based on the
      topographic patterns of the complementary task (correlation between one component
      with a linear combination of components from complementary conditions), of the
      same task in a second session and of a matched individual. Results again showed a
      high topographic similarity between conditions, as previously seen between
      reasoning and simple visual attention beta correlates. From an overall number of
      16 components representing brain activity obtained for the tasks (out of 60
      originally computed where the remaining were considered noise), over 92% could
      satisfactorily be explained by the complementary task. Although the similarity
      between sessions was significantly smaller than between tasks on each day, the
      similarity between sessions was statistically higher than that between subjects
      in a highly significant way. We discuss the possible biases of group spatial
      averaging and the emphasis on differences as opposed to similarities, and noise
      in a wide sense, as the main causes of hardly replicable findings on task-related
      forms of activity and the inconclusive state of a universal functional mapping of
      cortical association areas.

PMID- 29185110
TI  - Concurrent validity of photogrammetric and inclinometric techniques based on
      assessment of anteroposterior spinal curvatures.
AB  - PURPOSE: The purpose of the study was to investigate correlations between
      parameters of anteroposterior spinal curvatures in the sagittal plane, measured
      with the use of photogrammetric technique and inclinometer in healthy elderly
      women. METHODS: Randomized study involved 50 females, ranging from 50 to 70 years
      of age (mean 62.26 +/- 6.94); mean body mass index (BMI) 27.69 +/- 4.79. The
      examined parameters included angle of inclination in lumbosacral spine (ALFA),
      thoracolumbar transition (BETA), upper thoracic segment (GAMMA), angle of lumbar
      lordosis (LLA) and thoracic kyphosis (TKA). Results obtained with gravitational
      inclinometer were compared with those identified with photogrammetry method.
      Statistical analyses were performed with Mann-Whitney U test, regression analysis
      and Bland-Altman analysis. RESULTS: In Mann-Whitney U test, with correction due
      to continuity, no statistically significant differences for any variable were
      found. Regression analysis was significant only for the variable of BETA angle.
      Bland-Altman coefficient for the respective angles was: ALFA 2.0%, BETA 4%, GAMMA
      0%, LLA 2% and TKA 0%. CONCLUSIONS: The results acquired with gravitational
      inclinometer and with photogrammetric technique are comparable, as the parameters
      of anteroposterior spinal curvatures acquired with these two methods are found to
      be compatible in the case of measurements of lumbar lordosis and thoracic
      kyphosis.

PMID- 29185111
TI  - Factors influencing spinal sagittal balance, bone mineral density, and Oswestry
      Disability Index outcome measures in patients with rheumatoid arthritis.
AB  - PURPOSE: To identify the factors influencing spinal sagittal alignment, bone
      mineral density (BMD), and Oswestry Disability Index (ODI) outcome measures in
      patients with rheumatoid arthritis (RA). METHODS: We enrolled 272 RA patients to
      identify the factors influencing sagittal vertical axis (SVA). Out of this, 220
      had evaluation of bone mineral density (BMD) and vertebral deformity (VD) on the
      sagittal plane; 183 completed the ODI questionnaire. We collected data regarding
      RA-associated clinical parameters and standing lateral X-ray images via an ODI
      questionnaire from April to December 2012 at a single center. Patients with a
      history of spinal surgery or any missing clinical data were excluded. Clinical
      parameters included age, sex, body mass index, RA disease duration, disease
      activity score 28 erythrocyte sedimentation rate (DAS28-ESR), serum anti-cyclic
      citrullinated peptide antibody, serum rheumatoid factor, serum matrix
      metalloproteinase-3, BMD and treatment type at survey, such as methotrexate
      (MTX), biological disease-modifying anti-rheumatic drugs, and glucocorticoids. We
      measured radiological parameters including pelvic incidence (PI), lumbar lordosis
      (LL), and SVA. We statistically identified the factors influencing SVA, BMD, VD,
      and ODI using multivariate regression analysis. RESULTS: Multivariate regression
      analysis showed that larger SVA correlated with older age, higher DAS28-ESR, MTX
      nonuse, and glucocorticoid use. Lower BMD was associated with female, older age,
      higher DAS28-ESR, and MTX nonuse. VD was associated with older age, longer
      disease duration, lower BMD, and glucocorticoid use. Worse ODI correlated with
      older age, larger PI-LL mismatch or larger SVA, higher DAS28-ESR, and
      glucocorticoid use. CONCLUSIONS: In managing low back pain and spinal sagittal
      alignment in RA patients, RA-related clinical factors and the treatment type
      should be taken into consideration.

PMID- 29185112
TI  - Prospective multi-centric evaluation of upper cervical and infra-cervical
      sagittal compensatory alignment in patients with adult cervical deformity.
AB  - PURPOSE: Reciprocal mechanisms for standing alignment have been described in
      thoraco-lumbar deformity but have not been studied in patients with primary
      cervical deformity (CD). The purpose of this study is to report upper- and infra
      cervical sagittal compensatory mechanisms in patients with CD and evaluate their
      changes post-operatively. METHODS: Global spinal alignment was studied in a
      prospective database of operative CD patients. Inclusion criteria were any of the
      following: cervical kyphosis (CK) > 10 degrees , cervical scoliosis > 10 degrees
      , cSVA (C2-C7 Sagittal vertical axis) > 4 cm or CBVA (Chin Brow Vertical Angle) >
      25 degrees . For this study, patients who had previous fusion outside C2 to T4
      segments were excluded. Patients were sub-classified by increasing severity of
      cervical kyphosis [CL (cervical lordosis): < 0 degrees , CK-low 0 degrees -10
      degrees , CK-high > 10 degrees ] and cSVA (cSVA-low 0-4 cm, cSVA-mid 4-6 cm, cSVA
      high > 6 cm) and were compared for pre- and 3-month post-operative regional and
      global sagittal alignment to determine compensatory recruitment. RESULTS: 75 CD
      patients (mean age 61.3 years, 56% women) were included. Patients with
      progressively larger CK had a progressive increase in C0-C2 (CL = 34 degrees , CK
      low = 37 degrees , CK-high = 44 degrees , p = 0.004), C2Slope and T1Slope-CL (p <
      0.05). As the cSVA increased, there was progressive increase in C2Slope, T1Slope
      and TS-CL (p < 0.05) and patients compensated through increasing C0-C2 (cSVA-low
      = 33 degrees , cSVA-mid = 40 degrees , cSVA-high = 43 degrees , p = 0.007) and
      pelvic tilt (cSVA-low = 14.9 degrees , cSVA-mid = 24.1 degrees , cSVA-high = 24.9
      degrees , p = 0.02). At 3 months post-op, with significant improvement in
      cervical alignment, there was relaxation of C0-C2 (39 degrees -35 degrees , p =
      0.01) which positively correlated with magnitude of deformity correction.
      CONCLUSIONS: Patients with cervical malalignment compensate with upper cervical
      hyper-lordosis, presumably for the maintenance of horizontal gaze. As cSVA
      increases, patients also tend to exhibit increased pelvic retroversion. Following
      surgical treatment, there was relaxation of upper cervical compensation.

PMID- 29185113
TI  - Cross Validation of the Gambling Problem Severity Subscale of the Canadian
      Adolescent Gambling Index (CAGI/GPSS) on a Sample of Ontario High School
      Students.
AB  - This paper reports on the cross validation of the Gambling Problem Severity
      Subscale of the Canadian Adolescent Gambling Index (CAGI/GPSS). The CAGI/GPSS was
      included in a large school based drug use and health survey conducted in 2015.
      Data from students in grades 9-12 (ages 13-20 years) derived from the (N = 3369
      students). The CAGI/GPSS produced an alpha of 0.789. A principle component
      analysis revealed two eigenvalues greater than one. An oblique rotation revealed
      these components to represent consequences and over involvement. The CAGI/GPSS
      indicated that 1% of the students fell into the "red" category indicating a
      severe problem and an additional 3.3% scored in the "yellow" category indicating
      low to moderate problems. The CAGI/GPSS was shown to be significantly correlated
      with gambling frequency (r = 0.36), largest expenditure (r = 0.37), sex (more
      likely to be male) (r = -0.19), lower school marks (r = -0.07), hazardous
      drinking, (r = 0.16), problem video game play (r = 0.16), as well as substance
      abuse. The CAGI/GPSS was cross validated using a shorted version of the short
      SOGS, r = 0.48. In addition the CAGI/GPSS and short SOGS produced very similar
      patterns of correlations results. The results support the validity and
      reliability of the CAGI/GPSS as a measure of gambling problems among adolescents.

PMID- 29185114
TI  - Growth morphology of CL-20/HMX cocrystal explosive: insights from solvent
      behavior under different temperatures.
AB  - A 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) /1,3,5,7
      tetranitro-1,3,5,7-tetrazacyclooctane (HMX)-isopropanol (IPA) interfacial model
      was constructed to investigate the effect of temperature on cocrystal morphology.
      A constant volume and temperature molecular dynamics (NVT-MD) simulation was
      performed on the interfacial model at various temperatures (295-355 K, 20 K
      intervals). The surface electrostatic potential (ESP) of the CL-20/HMX cocrystal
      structure and IPA molecule were studied by the B3LYP method at 6-311++G (d, p)
      level. The surface energies, polarities, adsorption energy, mass density
      distribution, radial distribution function (RDF), mean square displacement (MSD)
      and relative changes of attachment energy were analyzed. The results show that
      polarities of (1 0 0) and (0 1 1) cocrystal surfaces may be more negative and
      affected by IPA solvent. The adsorption energy per area indicates that growth of
      the (1 0-2) face in IPA conditions may be more limited, while the (1 0 0) face
      tends to grow more freely. MSD and diffusion coefficient (D) analyses
      demonstrated that IPA molecules gather more easily on the cocrystal surface at
      lower temperatures, and hence have a larger effect on the growth of cocrystal
      faces. RDF analysis shows that, with the increasing of temperature, the strength
      of hydrogen bond interactions between cocrystal and solvent becomes stronger,
      being highest at 335 K for the (1 0 0) and (0 1 1) interfacial models. Results of
      relative changes of modified attachment energy show that (1 0 0) and (0 1 1)
      faces tends to be larger than other faces. Moreover, the predicted morphologies
      at 295 and 355 K are consistent with experimental values, proving that the CL
      20/HMX-IPA interfacial model is a reasonable one for this study. Graphical
      Abstract Construction of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12
      hexaazaisowurtzitane (CL-20) /1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX)
      isopropanol (IPA) interfacial model, analysis, and morphology prediction of
      cocrystal.

PMID- 29185115
TI  - The synergistic effect of nsP2-L618, nsP3-R117, and E2-K187 on the large plaque
      phenotype of chikungunya virus.
AB  - Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is the etiological agent
      of chikungunya fever. CHIKV re-emerged from 2004 onwards, and subsequently caused
      major outbreaks in many parts of the world including the Indian Ocean islands,
      Asia, and the Americas. In this study, a large plaque variant of CHIKV isolated
      from patient in Thailand was subjected to repeated cycles of plaque-purification
      in Vero cells. The resulting virus produced homogenous large plaques and showed a
      more pathogenic phenotype than the parental wild-type CHIKV. Whole genome
      analysis of the large plaque virus in comparison to parental isolate revealed a
      number of mutations, leading to the following amino acid changes: nsP2 (P618->L),
      nsP3 (G117->R), and E2 (N187->K). Eight recombinant CHIKVs were constructed to
      determine which amino acids mediated the large plaque phenotype. The results
      showed the recombinant virus which contains all three mutations, rCHK-L, produced
      significantly larger plaques than the other recombinant viruses (p < 0.01).
      Moreover, the plaque size of the other recombinant virus tended to be smaller if
      they contained only one or two of the large plaque associated mutations in the
      viral genome. In conclusion, the combination of all three residues (nsP2-L618,
      nsP3-R117, and E2-K187) is required to produce the large plaque phenotype of
      CHIKV.

PMID- 29185116
TI  - Standard, transepithelial and iontophoresis corneal cross-linking: clinical
      analysis of three surgical techniques.
AB  - BACKGROUND: To evaluate the clinical results of standard, transepithelial (TE)
      and iontophoresis (I) corneal cross-linking (CXL), in patients with progressive
      keratoconus. METHODS: Thirty eyes of 30 patients with progressive keratoconus
      treated by CXL (10 by standard-CXL, 10 by TE-CXL and 10 by I-TE-CXL) with 12
      months of follow-up. Pre- and postoperative ophthalmologic testing were:
      uncorrected distance visual acuity (UDVA), corrected distance visual acuity
      (CDVA), refractive examination (spherical error, spherical equivalent), corneal
      topography (corneal astigmatism, simulated maximum, minimum and average
      keratometry), aberrometry (coma and spherical aberration), pachymetry and
      endothelial cell density. RESULTS: In all groups, UDVA and CDVA improved
      significantly after treatment. Furthermore, a significant improvement in
      spherical error, spherical equivalent, topographic and aberrometric outcomes was
      observed in 3 groups at 1 year posttreatment. No significant variations were
      recorded in corneal thickness and endothelial cellular density. CONCLUSION: Our
      results showed efficacy, clinical and refractive stability after standard-CXL, TE
      CXL and iontophoresis-CXL.

PMID- 29185117
TI  - Algoriphagus formosus sp. nov., isolated from coastal sediment.
AB  - A Gram-stain negative, facultative anaerobic, non-motile, strongly orange
      pigmented and rod-shaped bacterium, designated XAY3209T, was isolated from a
      marine sediment sample collected from the coast of Weihai, China. Strain XAY3209T
      was found to grow optimally at 30  degrees C, at pH 7.0 and in the presence of
      2.0% (w/v) NaCl. Its genomic DNA G+C content was 41.9 mol%. On the basis of 16S
      rRNA gene sequence similarity, the novel isolate belongs to the family
      Cyclobacteriaceae and is related to the genus Algoriphagus. It shares 98.1% 16S
      rRNA sequence identity with Algoriphagus marincola, its close phylogenetic
      relative, but did not show similarities more than 97% with other members of the
      genus Algoriphagus with validly published names. It contained menaquinone-7 (MK
      7) as the sole respiratory quinone, iso-C15:0, iso-C17:1 omega9c and Summed
      feature 3 (C16:1 omega7c and/or iso-C15:0 2-OH) as the major fatty acids. The
      major polar lipids were phosphatidylethanolamine, one unidentified aminolipid,
      one unidentified phospholipid and five unidentified lipids. Results of
      physiological experiments, biochemical tests and genome average nucleotide
      identity value (with A. marincola MCCC 1F01203T) indicate that strain XAY3209T is
      genetically and phenotypically distinct from the species of the genus
      Algoriphagus with validly published names. Strain XAY3209T therefore represents a
      novel species, for which the name Algoriphagus formosus sp. nov. is proposed. The
      type strain is XAY3209T (= KCTC 52842T = MCCC 1H00189T).

PMID- 29185119
TI  - PRMT5 determines the sensitivity to chemotherapeutics by governing stemness in
      breast cancer.
AB  - PURPOSE: Acquired resistance to chemotherapeutic agents in breast cancer is a
      major clinical challenge. Recent studies have shown that the emergence of cancer
      stem cells contributes to the development of drug resistance, and the protein
      arginine methyltransferase 5 (PRMT5) was crucial for the maintenance of stemness.
      However, the roles of PRMT5 in breast cancer cell stemness and the development of
      cancer drug resistance have not been clarified. In this study, we investigated
      the effect of PRMT5 on the sensitivity to doxorubicin and cell stemness in breast
      cancer. METHODS: PRMT5 expression was assessed in a panel of breast cancer cell
      lines (MDA-MB-231, MCF7, T-47D, BT-474, Au-565) and normal mammal epithelial
      cells (MCF10A). For knockdown of PRMT5 expression, two pairs of shRNAs as well as
      a control shRNA were utilized. Meanwhile, the wild-type PRMT5 and its
      catalytically dead counterpart (R368A) were stably overexpressed in MDA-MB-231
      and MCF7 cells. The sensitivity to doxorubicin was determined by MTT assays,
      TUNEL assays, and Western blot analyses. To evaluate the degree of cell stemness,
      CD24/CD44-sorting and mammosphere formation experiments were performed. RESULTS:
      We demonstrated that PRMT5 regulates OCT4/A, KLF4, and C-MYC in breast cancer to
      govern stemness and affects the doxorubicin resistance of breast cancer.
      CONCLUSION: Our study suggests that PRMT5 may play an important role in the
      doxorubicin resistance of breast cancer.

PMID- 29185118
TI  - Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker
      into breast cancer screening.
AB  - PURPOSE: Due to limitations in the ability to identify non-progressive disease,
      ductal carcinoma in situ (DCIS) is usually managed similarly to localized
      invasive breast cancer. We used simulation modeling to evaluate the potential
      impact of a hypothetical test that identifies non-progressive DCIS. METHODS: A
      discrete-event model simulated a cohort of U.S. women undergoing digital
      screening mammography. All women diagnosed with DCIS underwent the hypothetical
      DCIS prognostic test. Women with test results indicating progressive DCIS
      received standard breast cancer treatment and a decrement to quality of life
      corresponding to the treatment. If the DCIS test indicated non-progressive DCIS,
      no treatment was received and women continued routine annual surveillance
      mammography. A range of test performance characteristics and prevalence of non
      progressive disease were simulated. Analysis compared discounted quality-adjusted
      life years (QALYs) and costs for test scenarios to base-case scenarios without
      the test. RESULTS: Compared to the base case, a perfect prognostic test resulted
      in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A
      perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with
      DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were
      sensitive to the performance characteristics of the prognostic test, the
      proportion of DCIS cases that were non-progressive in the model, and the
      frequency of mammography screening in the population. CONCLUSION: A prognostic
      test that identifies non-progressive DCIS would substantially reduce treatment
      costs but result in only modest improvements in quality of life when averaged
      over all DCIS cases.

PMID- 29185120
TI  - Characterization of a novel germline BRCA1 splice variant, c.5332+4delA.
AB  - PURPOSE: Germline mutations in BRCA1 and BRCA2 confer a significant increase in
      risk for cancer, and determining pathogenicity of a BRCA variant can guide the
      clinical management of the disease. About 1/3 of BRCA1 variants reported in the
      public databases have uncertain clinical significance due to lack of conclusive
      evidence. This study aims to characterize a novel BRCA1 deletion affecting the +
      4 splice donor site identified in an individual with early-onset breast cancer.
      METHODS: The effect of BRCA1 c.5332+4delA variant on RNA splicing was evaluated
      by amplifying regions of BRCA1 from cDNA derived from the patient. The proportion
      of abnormal transcript in the total transcripts was quantified. Loss of
      heterozygosity (LOH) in tumor tissue was investigated using Sanger sequencing and
      fragment analysis. RESULTS: BRCA1 c.5332+4delA caused skipping of exon 21 in
      patient-derived samples. Semi-quantitative analysis indicated that this aberrant
      RT-PCR product accounts for about 40% of the total transcript levels. Loss of
      heterozygosity (LOH) was observed in patient's tumor tissue. CONCLUSIONS: Our
      results indicate that the BRCA1 c.5332+4delA variant contributes to cancer
      predisposition through disruption of normal mRNA splicing. We classify this
      variant as likely pathogenic.

PMID- 29185121
TI  - Acetylene chain reaction on hydrogenated boron nitride monolayers: a density
      functional theory study.
AB  - Spin-polarized first-principles total-energy calculations have been performed to
      investigate the possible chain reaction of acetylene molecules mediated by
      hydrogen abstraction on hydrogenated hexagonal boron nitride monolayers.
      Calculations have been done within the periodic density functional theory (DFT),
      employing the PBE exchange correlation potential, with van der Waals corrections
      (vdW-DF). Reactions at two different sites have been considered: hydrogen
      vacancies on top of boron and on top of nitrogen atoms. As previously calculated,
      at the intermediate state of the reaction, when the acetylene molecule is
      attached to the surface, the adsorption energy is of the order of -0.82 eV and 
      0.20 eV (measured with respect to the energy of the non interacting molecule
      substrate system) for adsorption on top of boron and nitrogen atoms,
      respectively. After the hydrogen abstraction takes place, the system gains
      additional energy, resulting in adsorption energies of -1.52 eV and -1.30 eV,
      respectively. These results suggest that the chain reaction is energetically
      favorable. The calculated minimum energy path (MEP) for hydrogen abstraction
      shows very small energy barriers of the order of 5 meV and 22 meV for the
      reaction on top of boron and nitrogen atoms, respectively. Finally, the density
      of states (DOS) evolution study helps to understand the chain reaction mechanism.
      Graphical abstract Acetylene chain reaction on hydrogenated boron nitride
      monolayers.

PMID- 29185122
TI  - Genomic variations in the counterpart normal controls of lung squamous cell
      carcinomas.
AB  - Lung squamous cell carcinoma (LUSC) causes approximately 400 000 deaths each year
      worldwide. The occurrence of LUSC is attributed to exposure to cigarette smoke,
      which induces the development of numerous genomic abnormalities. However, few
      studies have investigated the genomic variations that occur only in normal
      tissues that have been similarly exposed to tobacco smoke as tumor tissues. In
      this study, we sequenced the whole genomes of three normal lung tissue samples
      and their paired adjacent squamous cell carcinomas.We then called genomic
      variations specific to the normal lung tissues through filtering the genomic
      sequence of the normal lung tissues against that of the paired tumors, the
      reference human genome, the dbSNP138 common germline variants, and the variations
      derived from sequencing artifacts. To expand these observations, the whole exome
      sequences of 478 counterpart normal controls (CNCs) and paired LUSCs of The
      Cancer Genome Atlas (TCGA) dataset were analyzed. Sixteen genomic variations were
      called in the three normal lung tissues. These variations were confirmed by
      Sanger capillary sequencing. A mean of 0.5661 exonic variations/Mb and 7.7887
      altered genes per sample were identified in the CNC genome sequences of TCGA. In
      these CNCs, C:G->T:A transitions, which are the genomic signatures of tobacco
      carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide
      changes. Twenty five genes in CNCs had a variation rate that exceeded 2%,
      including ARSD (18.62%), MUC4 (8.79%), and RBMX (7.11%). CNC variations in CTAGE5
      and USP17L7 were associated with the poor prognosis of patients with LUSC. Our
      results uncovered previously unreported genomic variations in CNCs, rather than
      LUSCs, that may be involved in the development of LUSC.

PMID- 29185123
TI  - Is Timing of Enrollment Associated with Birth Outcomes? Findings from a Healthy
      Start Program in Kansas.
AB  - Objective The Sedgwick County Healthy Babies Healthy Start (HBHS) program
      provides community-based services (including care coordination, interconception
      care and home visiting) aimed at reducing racial/ethnic disparities in poor birth
      outcomes. The purpose of this study is to assess the effectiveness of the
      Sedgwick County HBHS program by comparing the birth outcomes of program
      participants who enrolled prenatally and those who did not participate while
      pregnant. Methods In this retrospective cohort study, we used data drawn from the
      Sedgwick County HBHS program. The sample included 280 clients who were enrolled
      in the Sedgwick County HBHS program between September 2014 and December 2015. We
      performed logistic regression analyses to assess the associations between
      enrollee type (prenatal enrollee vs. interconceptional enrollee) and birth
      outcomes (low birth weight, preterm birth). Results The majority of the sample
      consisted of racial/ethnic minority women (32.1% non-Hispanic black, 31.8%
      Hispanic). After adjusting for covariates, women who enrolled in the Sedgwick
      County HBHS program prenatally were less likely than women who were not enrolled
      during pregnancy to have a preterm birth (OR 0.19, [CI 08, 0.43]) and deliver a
      low birth weight infant (OR 0.31, [CI 0.10, 0.97]). Conclusions for Practice
      Women, particularly minority women, who participate in the HBHS program
      experienced better birth outcomes than women who did not participate in the
      program during pregnancy. However, findings also suggest that interconceptional
      enrollees may stand to benefit from continued participation in the program.

PMID- 29185124
TI  - The role of DNA sequence in nucleosome breathing.
AB  - Roughly 3/4 of human genomes are sequestered by nucleosomes, DNA spools with a
      protein core, dictating a broad range of biological processes, ranging from gene
      regulation, recombination, and replication, to chromosome condensation.
      Nucleosomes are dynamical structures and temporarily expose wrapped DNA through
      spontaneous unspooling from either end, a process called site exposure or
      nucleosome breathing. Here we ask how this process is influenced by the
      mechanical properties of the wrapped DNA, which is known to depend on the
      underlying base pair sequence. Using a coarse-grained nucleosome model we
      calculate the accessibility profiles for site exposure. We find that the process
      is very sensitive to sequence effects, so that evolution could potentially tune
      the accessibility of nucleosomal DNA and would only need a small number of
      mutations to do so.

PMID- 29185125
TI  - Measuring childhood cancer late effects: evidence of a healthy survivor effect.
AB  - INTRODUCTION: Given considerable focus on health outcomes among childhood cancer
      survivors, we aimed to explore whether survivor bias is apparent during long-term
      follow-up of childhood cancer survivors. METHODS: We identified all 1-year
      survivors of cancer diagnosed before 20 years of age in Denmark, Finland,
      Iceland, and Sweden. From the general population, we randomly sampled a
      comparison cohort. Study individuals were followed for hospitalizations for
      diseases of the gastroenterological tract, endocrine system, cardiovascular
      system, or urinary tract from the start of the cancer registries to 2010. We
      estimated cumulative incidence with death as competing risk and used threshold
      regression to compare the hazards of the diseases of interest at ages 20, 40, 60,
      and 75 years. RESULTS: Our study included 27,007 one-year survivors of childhood
      cancer and 165,620 individuals from the general population. The cumulative
      incidence of all four outcomes was higher for childhood cancer survivors during
      early adulthood, but for three outcomes, the cumulative incidence was higher for
      the general population after age 55 years. The hazard ratios (HRs) decreased for
      all outcomes with increasing age, and for two of the outcomes, the hazards were
      higher for the general population at older ages (endocrine diseases: age-specific
      HRs = 3.0, 1.4, 1.0, 0.87; Cardiovascular diseases: age-specific HRs = 4.1, 1.4,
      0.97, 0.84). CONCLUSIONS: Our findings provide empirical evidence that survivor
      bias attenuates measures of association when comparing survivors with the general
      population. The design and analysis of studies among childhood cancer survivors,
      particularly as this population attains older ages, should account for survivor
      bias to avoid misinterpreting estimates of disease burden.

PMID- 29185126
TI  - Long-term outcome of congenital nephrotic syndrome after kidney transplantation
      in Japan.
AB  - BACKGROUND: Congenital nephrotic syndrome is difficult to manage, particularly
      the Finnish type (CNF), with patients experiencing severe edema, sepsis and
      thrombosis before kidney transplantation. Further, nephrosis and thrombosis
      remain problematic after transplantation. METHODS: Of 22 CNF patients managed at
      our hospital, 14 who underwent kidney transplantation were retrospectively
      studied. CNF was diagnosed according to standard criteria. RESULTS: The study
      population consisted of 3 males and 11 females. Mean gestation period was 36 +/-
      1.4 weeks and mean birth weight was 2442 +/- 454 g (mean placenta to body weight
      ratio: 0.4). All patients started dialysis at 2.4 +/- 1.3 years and underwent
      kidney transplantation at 5.2 +/- 2.0 years. The kidneys were donated by the
      parents (n = 13), and cadaver (n = 2), including overlap. Mean follow-up period
      after transplantation was 14.3 +/- 8.9 years, and mean age at last observation
      was 19.5 +/- 8.5 years. Two patients had recurrent proteinuria after kidney
      transplantation; one underwent retransplantation following graft failure and
      eventually required dialysis, while the second had complete remission after
      intensive immunosuppressive therapy. There were no cases of thrombosis or serious
      infections. Mean eGFR at the time of last observation was 57.3 +/- 16.5
      ml/min/1.73 m2, while mean height SD score was - 2.1 +/- 0.9 at the time of
      transplantation and - 1.5 +/- 1.5 at last observation. CONCLUSIONS: Long-term
      outcome in these 14 CNF patients showed satisfactory graft survival, improved
      height SD score, and favorable development. Although recurrent proteinuria after
      transplant was not predictive, it was associated with graft survival rate.

PMID- 29185127
TI  - Patient knowledge and adherence to maintenance hemodialysis: an International
      comparison study.
AB  - BACKGROUND: Non-adherence to hemodialysis (HD) is associated with increased
      morbidity and mortality. In this cross-sectional study, we compared correlates
      and rates of non-adherence between the US and Japan to determine if differences
      in patient knowledge about HD might account for international variation in
      adherence. METHODS: We evaluated 100 US and 116 Japanese patients on maintenance
      HD. Patient knowledge was scored based on the identification of their vascular
      access, dry weight, cause of kidney disease, and >= 3 phosphorus- and potassium
      rich foods. Patients were considered non-adherent if they missed > 3% of HD
      sessions in 3 months. RESULTS: 23% of the US and none of the Japanese patients
      were non-adherent. Using logistic regression, we found that in the US non
      adherence was more common in black patients [Odds ratio (OR) 3.98; 95% confidence
      interval (CI) 1.42-11.22], while high school graduates (OR 0.20; 95% CI 0.05
      0.81) and those on the transplant waiting list (OR 0.25; 95% CI 0.083-0.72) were
      less likely to miss their treatments. There was no significant association
      between knowledge and non-adherence in the US. However, Japanese patients had
      significantly higher levels of HD knowledge than US patients after adjusting for
      age (p < 0.001). CONCLUSION: Age-adjusted HD knowledge was higher and non
      adherence rates were lower in Japan vs. the US. However, because of the
      unexpected finding of 100% adherence in Japan, we were unable to formally test
      whether knowledge was significantly associated with adherence across both
      countries. Further research is needed to understand the reasons behind the higher
      non-adherence rates in the US.

PMID- 29185128
TI  - Triphenylphosphine-based functional porous polymer as an efficient heterogeneous
      catalyst for the synthesis of cyclic carbonates from CO2.
AB  - A novel triphenylphosphine-based porous polymer (TPDB) with a high Brunauer
      Emmett-Teller (BET) surface area was synthesized through Friedel-Crafts
      alkylation of triphenylphosphine and alpha-dibromo-p-xylene. Then, the functional
      hydroxyl groups were successfully grafted onto the polymer framework by post
      modification of TPDB with 3-bromo-1-propanol (BP) and triethanolamine (TEA). The
      resulting sample TPDB-BP-TEA was characterized by various techniques such as FT
      IR, TG, SEM, EDS mapping, ICP-MS, and N2 adsorption-desorption. This new polymer
      was tested as the catalyst in the solvent-free cycloaddition reaction of CO2 with
      epoxides, which exhibited excellent performance, with high yield, selectivity,
      and stable recyclability for several catalytic cycles. The comparison experiment
      results demonstrate that the bromide ions and hydroxyl groups, as well as high
      surface area, are key factors in improving the catalytic activity of this new
      catalyst.

PMID- 29185129
TI  - Nostoc calcicola extract improved the antioxidative response of soybean to cowpea
      aphid.
AB  - BACKGROUND: Soybean (Glycine max (L.) Merr. cv. "Nam Dan") is one of the most
      valuable crops in agricultural production in Nghe An province (Vietnam). Our
      previous study revealed that extract of the cyanobacterium strain Nostoc
      calcicola HN9 expressed positive effect on growth and development, and raised
      soybean productivity (Tran et al. in Proceeding of Vietnam national conference of
      research on biology, Da Nang, 2016). We hypothesized that N. calcicola HN9 would
      improve the defense responses of G. max cv. "Nam Dan" to cowpea aphid (Aphis
      craccivora Koch)-a serious pest of leguminous crops. RESULTS: Infestation of A.
      craccivora caused oxidative stress in leaves of G. max cv. "Nam Dan". A strong
      generation of endogenous reactive oxygen species (ROS) such as superoxide anion
      radical (O 2.- ) and hydrogen peroxide (H2O2) resulted in the cellular damages in
      the aphid-infested leaves through high levels of injury percentage and lipid
      peroxidation. To protect from aphid attack themselves, soybean plants triggered
      the antioxidant defense systems, in which, enzymatic antioxidants such as
      superoxide dismutase (SOD, 1.15.1.1), catalase (CAT, 1.11.1.6) and GPx (EC
      1.11.1.9) were strongly accumulated to reduce the toxic effects of ROS.
      Components of N. calcicola HN9 extract might strengthen the defensive capability
      of G. max cv. "Nam Dan" to cowpea aphid infestation via establishing the chemical
      constraints on oxidative stress. Under effect of cyanobacteria extract,
      generation of O 2.- and H2O2 was strictly limited, activities of SOD, CAT and GPx
      were remarkably accumulated in the aphid-infested leaves leading to a significant
      reduction of oxidative damages. CONCLUSIONS: Nostoc calcicola HN9 extract
      probably not only controlled the generation and effects of O 2.- and H2O2 but
      also augmented the accumulated activity of SOD, CAT and GPx in soybean leaves
      that allowed them to control oxidative stress, contributed to increase the
      resistance of G. max cv. "Nam Dan" to A. craccivora. The improvement of
      cyanobacteria extract on the antioxidative response of soybean "Nam Dan" to
      cowpea aphid can be a novel aspect to contribute to current knowledge regarding
      the soybean-aphid interaction.

PMID- 29185130
TI  - Increased lipid and protein oxidation and lowered anti-oxidant defenses in
      systemic lupus erythematosus are associated with severity of illness,
      autoimmunity, increased adhesion molecules, and Th1 and Th17 immune shift.
AB  - This study investigated nitro-oxidative stress in patients with systemic lupus
      erythematosus (SLE) in association with disease activity, immune-inflammatory
      biomarkers, and adhesion molecules. Two-hundred-four patients with SLE and 256
      healthy volunteers were enrolled in this case-control study, which measured nitro
      oxidative stress biomarkers, including lipid peroxides (LOOH), advanced oxidation
      protein products (AOPPs), nitric oxide metabolites (NOx), sulfhydryl (-SH)
      groups, products of deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) oxidative
      degradation, and total radical-trapping anti-oxidant parameter (TRAP). Also
      measured were anti-nuclear antibodies (ANAs), antibodies against double-stranded
      DNA (dsDNA), plasma levels of diverse cytokines, C-reactive protein, and adhesion
      molecules. LOOH (p < 0.001) and AOPP (p < 0.001) were significantly higher, while
      TRAP was significantly lower (p < 0.001) in SLE patients than in controls. AOPP
      and LOOH were significantly and positively associated with SLE disease activity
      index (SLEDAI) scores, anti-nuclear antibodies, and antibodies against double
      stranded DNA (anti-dsDNA) levels, while TRAP was significantly and inversely
      correlated with SLEDAI, ANA, and dsDNA antibody levels. There were significant
      positive associations between AOPP and LOOH and immune-inflammatory markers,
      indicating T helper (Th)-17 and Th1 bias and Th1 + Th17/Th2 ratio (p = 0.002 and
      p = 0.001, respectively). AOPP and LOOH (positively) and TRAP (inversely) were
      associated with adhesion molecule expression. A model predicting SLE was computed
      showing that, using LOOH, AOPP, NOx, adhesion molecules, and body mass index,
      94.2% of the patients were correctly classified with a specificity of 91.5%.
      Increased nitro-oxidative stress takes part in the (auto)immune pathophysiology
      of SLE and modulates severity of illness and adhesion molecule expression.

PMID- 29185132
TI  - Electrospinning onto Insulating Substrates by Controlling Surface Wettability and
      Humidity.
AB  - We report a simple method for electrospinning polymers onto flexible, insulating
      substrates by controlling the wettability of the substrate surface. Water
      molecules were adsorbed onto the surface of a hydrophilic polymer substrate by
      increasing the local humidity around the substrate. The adsorbed water was used
      as the ground electrode for electrospinning. The electrospun fibers were
      deposited only onto hydrophilic areas of the substrate, allowing for patterning
      through wettability control. Direct writing of polymer fiber was also possible
      through near-field electrospinning onto a hydrophilic surface.

PMID- 29185131
TI  - Nimbolide attenuate the lipid accumulation, oxidative stress and antioxidant in
      primary hepatocytes.
AB  - Nimbolide is a bioactive compound found in Azadirachta indica. This work was
      devised to investigate the potential effects of nimbolide on intracellular lipid
      deposition and its associated redox modulation in primary hepatocytes (Heps).
      Lipid accumulation was induced in Heps by supplementing 1 mM oleic acid for 24 h
      which was marked by significant accumulation of lipids. The results demonstrated
      that nimbolide can decrease intracellular cholesterol, free fatty acids and
      triglycerides. Nimbolide may also improve hepatocytes function through its
      antioxidant effects by inhibiting oxidative DNA damage and lipid peroxidation by
      curtailing the reactive oxygen species levels. Further it also restore the
      mitochondrial potential, improving the endogenous antioxidant levels such as GSH
      and antioxidant enzyme activities. Nimbolide increased (P < 0.05) liver X
      receptor-alpha (LXRalpha), peroxisome proliferator-activated receptor-gamma
      (PPARgamma) and sterol regulatory element-binding protein-1c (SREBP1c) gene
      expression in Heps. The biological significance of nimbolide may involve
      hypolipidemic effect, lipid peroxidation inhibition, DNA damage inhibition, ROS
      inhibition, restoring mitochondrial function, increases in GSH and SOD & CAT
      activities, and direct regulation of LXRalpha, PPARgamma and SREBP1c gene
      expression. Nimbolide may be used as effective lipid lowering compound and lipid
      deposition-induced Heps changes.

PMID- 29185133
TI  - A resistance exercise program improves functional capacity of patients with
      psoriatic arthritis: a randomized controlled trial.
AB  - The objective of this study is to assess the effectiveness of resistance training
      in patients with psoriatic arthritis (PsA). The study is a randomized controlled
      trial with 41 patients aged between 18 and 65 years with diagnosis of psoriatic
      arthritis (PsA). The patients were randomized into the following: intervention
      group (IG) and control group (CG). The IG underwent resistance exercise twice a
      week, for 12 weeks. The CG remained with the conventional drug therapy. The
      outcome measurements were the following: BASFI and HAQ-S for functional capacity,
      one maximum repetition test (1RM) for muscle strength, SF-36 questionnaire for
      general quality of life, and BASDAI and DAS-28 for disease activity. The
      evaluations were done by a blinded evaluator at baseline (T0) after 6 (T6) and 12
      weeks (T12). At baseline, the groups were homogeneous regarding clinical and
      demographic characteristics. The IG significantly improved functional capacity
      measured by HAQ-S and disease activity measured by BASDAI, compared to CG, at
      week 12. Regarding quality of life, the IG improved the domains "pain" and
      "general health status" compared to CG (p < 0.05). There was improvement in
      muscular strength in almost all exercises in IG, except in the exercise for
      biceps. However, there were statistical differences between groups only on
      exercise "leg extension" in IG compared to CG. Resistance training is effective
      in improving functional capacity, disease activity, and quality of life of
      patients with psoriatic arthritis. The clinical improvements were not coupled to
      significant changes in muscular strength.

PMID- 29185134
TI  - When is the best moment to apply photobiomodulation therapy (PBMT) when
      associated to a treadmill endurance-training program? A randomized, triple
      blinded, placebo-controlled clinical trial.
AB  - Photobiomodulation therapy (PBMT) employing low-level laser therapy (LLLT) and/or
      light emitting diode therapy (LEDT) has emerged as an electrophysical
      intervention that could be associated with aerobic training to enhance beneficial
      effects of aerobic exercise. However, the best moment to perform irradiation with
      PBMT in aerobic training has not been elucidated. The aim of this study was to
      assess the effects of PBMT applied before and/or after each training session and
      to evaluate outcomes of the endurance-training program associated with PBMT.
      Seventy-seven healthy volunteers completed the treadmill-training protocol
      performed for 12 weeks, with 3 sessions per week. PBMT was performed before
      and/or after each training session (17 sites on each lower limb, using a cluster
      of 12 diodes: 4 * 905 nm super-pulsed laser diodes, 4 * 875 nm infrared LEDs, and
      4 * 640 nm red LEDs, dose of 30 J per site). Volunteers were randomized in four
      groups according to the treatment they would receive before and after each
      training session: PBMT before + PBMT after, PBMT before + placebo after, placebo
      before + PBMT after, and placebo before + placebo after. Assessments were
      performed before the start of the protocol and after 4, 8, and 12 weeks of
      training. Primary outcome was time until exhaustion; secondary outcome measures
      were oxygen uptake and body fat. PBMT applied before and after aerobic exercise
      training sessions (PBMT before + PBMT after group) significantly increased (p <
      0.05) the percentage of change of time until exhaustion and oxygen uptake
      compared to the group treated with placebo before and after aerobic exercise
      training sessions (placebo before + placebo after group) at 4th, 8th, and 12th
      week. PBMT applied before and after aerobic exercise training sessions (PBMT
      before + PBMT after group) also significantly improved (p < 0.05) the percentage
      of change of body fat compared to the group treated with placebo before and after
      aerobic exercise training sessions (placebo before + placebo after group) at 8th
      and 12th week. PBMT applied before and after sessions of aerobic training during
      12 weeks can increase the time-to-exhaustion and oxygen uptake and also decrease
      the body fat in healthy volunteers when compared to placebo irradiation before
      and after exercise sessions. Our outcomes show that PBMT applied before and after
      endurance-training exercise sessions lead to improvement of endurance three times
      faster than exercise only.

PMID- 29185135
TI  - Disease-modifying treatments modulate myeloid cells in multiple sclerosis
      patients.
AB  - The role of myeloid cells in the pathogenesis of MS is determined by the
      polarization they acquire after activation, and mediated by release of
      extracellular vesicles (MVs). We assessed the effects of treatments for MS on
      activation and polarization of myeloid cells. MVs levels and markers of
      polarization of myeloid cells have been assessed at baseline and up to 6 months
      after the start of a MS treatment. Patients had higher levels of MVs than
      controls, and these increased significantly over 6 months under natalizumab.
      Interferon beta-1a significantly decreased M1 pro-inflammatory marker IL1beta and
      upregulated Trem2, a receptor important for debris clearance; both interferon
      beta-1a and fingolimod decreased pro-inflammatory marker IL6. Current treatments
      for MS significantly modulate myeloid cells activity.

PMID- 29185137
TI  - Chlorophyll fluorescence as a tool for nutrient status identification in rapeseed
      plants.
AB  - In natural conditions, plants growth and development depends on environmental
      conditions, including the availability of micro- and macroelements in the soil.
      Nutrient status should thus be examined not by establishing the effects of single
      nutrient deficiencies on the physiological state of the plant but by combinations
      of them. Differences in the nutrient content significantly affect the
      photochemical process of photosynthesis therefore playing a crucial role in
      plants growth and development. In this work, an attempt was made to find a
      connection between element content in (i) different soils, (ii) plant leaves,
      grown on these soils and (iii) changes in selected chlorophyll a fluorescence
      parameters, in order to find a method for early detection of plant stress
      resulting from the combination of nutrient status in natural conditions. To
      achieve this goal, a mathematical procedure was used which combines principal
      component analysis (a tool for the reduction of data complexity), hierarchical k
      means (a classification method) and a machine-learning method-super-organising
      maps. Differences in the mineral content of soil and plant leaves resulted in
      functional changes in the photosynthetic machinery that can be measured by
      chlorophyll a fluorescent signals. Five groups of patterns in the chlorophyll
      fluorescent parameters were established: the 'no deficiency', Fe-specific
      deficiency, slight, moderate and strong deficiency. Unfavourable development in
      groups with nutrient deficiency of any kind was reflected by a strong increase in
      F o and DeltaV/Deltat 0 and decline in phi Po, phi Eo delta Ro and phi Ro. The
      strong deficiency group showed the suboptimal development of the photosynthetic
      machinery, which affects both PSII and PSI. The nutrient-deficient groups also
      differed in antenna complex organisation. Thus, our work suggests that the
      chlorophyll fluorescent method combined with machine-learning methods can be
      highly informative and in some cases, it can replace much more expensive and time
      consuming procedures such as chemometric analyses.

PMID- 29185138
TI  - Barbados Blackbelly: the Caribbean ovine genetic resource.
AB  - Ovine production is one of the most important activities in animal production in
      tropical regions. The Barbados Blackbelly, a very interesting genetic resource,
      particularly well adapted to a harsh home environment in the humid tropics of the
      Caribbean. This review concerns this breed. It comprises aspects related to the
      breed history and standards and most importantly its reproductive and productive
      performances and gastrointestinal parasite tolerance in the Caribbean, North
      America and Central America and their introduction and use in crossbred trials in
      other regions of the tropics.

PMID- 29185139
TI  - Body weight change of Abergelle breed and Abergelle crossbred goats fed hay
      supplemented with different level of concentrate mixture.
AB  - The experiment was conducted at Sekota District using 36 intact yearling males of
      pure Abergelle breed and Abergelle crossbred goats (50%) with a mean live weight
      of 18.92 +/- 0.72 kg (mean +/- SE). The objective of the experiment was to
      evaluate the effect of different levels of concentrate mixture supplementation on
      feed intake, live weight gain, and economic gain of the breeds. Goats were
      blocked based on initial body weight and were randomly assigned to the dietary
      treatments. The experimental design was a 2 * 3 factorial in RCBD (randomized
      complete block design). The treatments included ad libitum feeding of local grass
      hay and supplementation with three levels (184, 368, and 552 g/day) of
      concentrate mixture. The experiment consisted of 90 days of feeding. Daily, total
      dry matter and CP (crude protein) intakes were affected by diet and genotype (P <
      0.01). Significant decrease (P < 0.001) in hay intake was observed as the level
      of the supplement increased. Besides, substitution rate increased with increasing
      levels of supplementation. Average daily body weight gains were significantly
      impacted only by diet. Animals fed on 184 significantly lower weights, while
      nonsignificant difference was observed in live weight gain between 368 and 552
      supplemented group. Supplementation of 368 concentrate mix significantly improved
      (P < 0.05) feed intake, daily weight gain, and feed conversion efficiency.
      Supplementation of 368 g/day had showed significantly higher net return for both
      goat breeds. However, the Abergelle breed was significantly better in net profit
      and sensitivity than the crossbreed. Both genotypes performed better with the
      diet containing 368 g/day than that with 184 and 552 g/day of concentrate
      supplementation.

PMID- 29185136
TI  - Molecular simulations of cellular processes.
AB  - It is, nowadays, possible to simulate biological processes in conditions that
      mimic the different cellular compartments. Several groups have performed these
      calculations using molecular models that vary in performance and accuracy. In
      many cases, the atomistic degrees of freedom have been eliminated, sacrificing
      both structural complexity and chemical specificity to be able to explore slow
      processes. In this review, we will discuss the insights gained from computer
      simulations on macromolecule diffusion, nuclear body formation, and processes
      involving the genetic material inside cell-mimicking spaces. We will also discuss
      the challenges to generate new models suitable for the simulations of biological
      processes on a cell scale and for cell-cycle-long times, including non
      equilibrium events such as the co-translational folding, misfolding, and
      aggregation of proteins. A prominent role will be played by the wise choice of
      the structural simplifications and, simultaneously, of a relatively complex
      energetic description. These challenging tasks will rely on the integration of
      experimental and computational methods, achieved through the application of
      efficient algorithms. Graphical abstract.

PMID- 29185140
TI  - Community-based tsetse fly control minimizes the effect of trypanosomosis on
      livestock in Metekel zone, Ethiopia.
AB  - Tsetse-related trypanosomosis threatens integrated crop-livestock production
      system in Ethiopia. Metekel zone is among the tsetse-infested areas in Ethiopia.
      Community-based tsetse fly and trypanosomosis control using targets was conducted
      from June 2011 to May 2012 in the zone. In coordination with the control project,
      a questionnaire survey was administered to assess the economic importance of the
      tsetse fly and trypanosomosis control conducted in the Zone. On average, there
      were 3 livestock deaths/household before control and this was decreased to 0.07
      after control. This death was contributed from all possible livestock diseases. A
      household loss 4380 (95% CI = 4223.98-4541.79) EB (1 US$ = 17.9 EB) only due to
      the deaths of his/her livestock was reduced to 90.78 (95% CI = 89.15-92.42) EB
      after control. Morbidity of oxen in the study areas was significantly decreased
      by 70.7%. As a result, the monetary loss to rent for healthy draught oxen was
      decreased by 96.4%. When a household with one cattle harvest 10.9 quintals (1090
      kg), his neighbor's household with ten cattle maximize his/her yield to about
      50.5 quintals (5050 kg) of crops indicating that trypanosomosis has great
      economic impact in crop-livestock production system. As the community-based
      tsetse fly control approach is simple, cost effective, and appropriate for
      riverine tsetse species, we conclude that farmers can minimize the negative
      impact of tsetse flies and trypanosomosis in the tsetse-infested areas of African
      countries.

PMID- 29185141
TI  - Tip-cell behavior is regulated by transcription factor FoxO1 under hypoxic
      conditions in developing mouse retinas.
AB  - Forkhead box protein O1 (FoxO1) is a transcription factor and a critical
      regulator of angiogenesis. Various environmental stimuli, including growth
      factors, nutrients, shear stress, oxidative stress and hypoxia, affect FoxO1
      subcellular localization and strongly influence its transcriptional activity;
      however, FoxO1-localization patterns in endothelial cells (ECs) during
      development have not been clarified in vivo. Here, we reported that FoxO1
      expression was observed in three layers of angiogenic vessels in developing mouse
      retinas and that among these layers, the front layer showed high levels of FoxO1
      expression in the nuclei of most tip ECs. Because tip ECs migrate toward the
      avascular hypoxic area, we focused on hypoxia as a major stimulus regulating
      FoxO1 subcellular localization in tip cells. In cultured ECs, FoxO1 accumulated
      into the nucleus under hypoxic conditions, with hypoxia also inducing expression
      of tip-cell-specific genes, including endothelial-specific molecule 1 (ESM1),
      which was suppressed by FoxO1 knockdown. Additionally, in murine models, EC
      specific FoxO1 deletion resulted in reduced ESM1 expression and suppressed tip
      cell migration during angiogenesis. These findings indicated roles for FoxO1 in
      tip-cell migration and that its transcriptional activity is regulated by hypoxia.

PMID- 29185142
TI  - Initial and long term impact of a multi-disciplinary task force in the diagnosis
      and management of heparin-induced thrombocytopenia.
AB  - Many medical centers are faced with a major challenge in making an accurate
      diagnosis of heparin-induced thrombocytopenia (HIT) and ensuring appropriate
      changes in management strategy in line with guideline recommendations. We report
      the initial and long-term impact and challenges of institution-wide changes in
      the diagnosis and management of HIT in the inpatient setting at an academic
      medical center. We established a HIT Task Force, consisting of a
      multidisciplinary team of non-malignant hematologists, nursing, pharmacist,
      pathology, blood bank and clinical lab informatics. Changes were implemented from
      2011 to 2012. In 2013, testing for PF4 and SRA decreased by 37.5 and 85%,
      respectively. 100% of positive PF4 received an automatic hematology consult to
      guide management, leading to a 78% reduction in the use of direct thrombin
      inhibitors. Annual audits in the subsequent years demonstrated increasing testing
      for HIT due to changes in the electronic ordering system. Through continuous
      monitoring, these shortfalls were detected and intervene early on with continued
      success. The implementation of a centralized hospital-wide protocol via a
      multidisciplinary task force that coordinates testing and treatment of patients
      suspected of having HIT led to a substantial reduction in PF4 and SRA testing, as
      well as use of DTIs, resulting in a safe and cost-effective approach for the
      diagnosis and treatment of HIT. Our study highlights the important of continuous
      monitoring to maintain the improvements made. Despite our initial success, annual
      re-auditing allowed for early detection of challenges, which then allowed
      appropriate early intervention.

PMID- 29185143
TI  - Association between short- and medium-term air pollution exposure and risk of
      mortality after intravenous thrombolysis for stroke.
AB  - The exposure to air pollutants may increase both incidence and mortality of
      stroke. We aimed to investigate the association of short- and medium-term
      exposure to particulate matter (PM) and nitrogen dioxide (NO2) with the outcome
      of intravenous thrombolysis (IVT) for stroke. We conducted a retrospective
      analysis based on data prospectively collected from 944 consecutive IVT-treated
      stroke patients. The main outcome measure was 3-month mortality. The secondary
      outcome measures were causes of neurological deterioration (>= 1 NIHSS point from
      baseline or death < 7 days), including intracerebral hemorrhage, cerebral edema
      (CED), and persistence or new appearance of hyperdense cerebral artery sign. In
      the adjusted model, higher PM2.5 and PM10 values in the last 3 days and 4 weeks
      before stroke were independently associated with higher mortality rate [hazard
      ratio (HR) 1.014, 95% confidence intervals (CI) 1.005-1.024, p = 0.003; HR 1.079,
      95% CI 1.055-1.103, p = 0.001; HR 1.019, 95% CI 1.005-1.032, p = 0.008; and HR
      1.015, 95% CI 1.004-1.027, p = 0.007; respectively]. Higher PM2.5 and PM10 values
      in the last 4 weeks were associated with higher CED rate [odd ratio (OR) 1.023,
      95% CI 1.007-1.040, p = 0.006; and OR 1.017, 95% CI 1.003-1.032, p = 0.021;
      respectively]. No significant association between PM or NO2 and other causes of
      neurological deterioration was observed. Higher exposure to PM in the last 3 days
      and 4 weeks before stroke may be independently associated with 3-month mortality
      after IVT. Higher exposure to PM in the last 4 weeks before stroke may also be
      independently associated with CED after IVT.

PMID- 29185144
TI  - Bond strength of adhesive systems to sound and demineralized dentin treated with
      bioactive glass ceramic suspension.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of a
      Biosilicate(r), associated with dentin adhesive system, on microtensile bond
      strength (MUTBS) to sound and demineralized dentin. MATERIALS AND METHODS: Eighty
      sound-extracted molars had their middle occlusal dentin exposed. In forty teeth,
      dentin was artificially demineralized (pH cycling). Sound and demineralized
      dentin teeth were separated into four groups (n = 10), according to the substrate
      treatment before restoration: Group 1-total-etching adhesive Adper TM Single bond
      2 (ASB) + Biosilicate(r), Group 2-ASB (without Biosilicate(r)), Group 3-AdheSE
      self-etching adhesive system (AdSE) + Biosilicate(r), and Group 4-AdSE (without
      Biosilicate(r)). Each tooth was restored with a hybrid composite and stored in
      water at 37  degrees C for 6 months. After water aging, teeth were cut in sticks
      (~ 1 mm2 cross-sectional area) and all samples were submitted to MUTBS test. The
      fracture modes of the samples were analyzed by stereomicroscopy. The
      representatively fractured samples were observed by scanning electron microscopy.
      Representative samples of each group were analyzed on energy dispersive X-ray
      spectrometry (EDX). The MUTBS and Ca-P ratio values were analyzed by 2-way ANOVA,
      Bonferroni, and Tukey test, respectively, p < .05. RESULTS: ASB + Biosilicate(r)
      presented the highest MUTBS values (p < .05), and lowest MUTBS values (p < .05)
      were found in AdSE Group. There was no statistical difference (p < .05) on MUTBS
      when substrates were compared, except for Group 2. The fracture pattern analysis
      showed prevalence of adhesive fractures in all groups. CONCLUSION: Biosilicate(r)
      enhanced bond strength of self-etching and etch-and-rinse adhesives to sound and
      demineralized dentin. CLINICAL RELEVANCE: Bioactive glass ceramic suspension
      could be recommended to be used to improve the dentin bond strengths of the total
      etching and self-etching adhesives after acid-etching and priming.

PMID- 29185145
TI  - Development of a novel bioactive glass for air-abrasion to selectively remove
      orthodontic adhesives.
AB  - OBJECTIVES: To develop a novel, bioactive glass for removing residual orthodontic
      adhesive via air-abrasion, following bracket debonding, and to evaluate its
      effectiveness against a proprietary bioactive glass 45S5(SylcTM)-air-abrasion,
      and a slow-speed tungsten carbide (TC) bur. MATERIALS AND METHODS: Three glasses
      were prepared and their bioactivity was proved. One novel glass (QMAT3) was
      selected due to its appropriate hardness, lower than that of enamel/45S5(SylcTM).
      Sixty extracted human premolars were randomly assigned to adhesive removal using:
      (a) QMAT3-air-abrasion, (b) 45S5(SylcTM)-air-abrasion, and (c) TC bur, which were
      further subdivided (n = 10) based on the adhesive used (Transbond XTTM or Fuji
      Ortho LCTM). Enamel roughness was assessed using scanning electron microscopy
      (SEM) and non-contact profilometry before bracket bonding, after removing
      residual adhesive following bracket debonding and after polishing. RESULTS: QMAT3
      formed apatite faster (6 h) than 45S5(SylcTM) (24 h) in Tris solution. QMAT3-air
      abrasion gave the lowest enamel roughness (Ra) after removing the adhesives. SEM
      images showed a pitted, roughened enamel surface in the TC bur group and to a
      lesser extent with 45S5(SylcTM), while a virtually smooth surface without any
      damage was observed in the QMAT3-air-abrasion group. The time taken for adhesive
      removal with QMAT3 was comparable to 45S5(SylcTM) but was twice as long with the
      TC bur. CONCLUSIONS: QMAT3-air-abrasion is a promising technique for selective
      removal of adhesives without inducing tangible enamel damage. CLINICAL RELEVANCE:
      A novel bioactive glass has been developed as an alternative to the use of TC
      burs for orthodontic adhesive removal.

PMID- 29185146
TI  - Lack of association between ENAM gene polymorphism and dental caries in primary
      and permanent teeth in Czech children.
AB  - OBJECTIVES: The enamelin gene (ENAM) polymorphism (rs12640848) was recently
      associated with dental caries in primary teeth in Polish children. The aims of
      the present study were to prove this association in primary dentition and to find
      a possible effect of this variant on caries development in permanent dentition in
      Czech children. MATERIALS AND METHODS: This study comprised 905 Czech children.
      Totally, 187 children aged 2-6 years with primary dentition [78 healthy subjects
      (with decayed/missing/filled teeth, dmft = 0) and 109 patients with early
      childhood caries (ECC; dmft >= 1)] were included in this case-control study. In
      addition, 177 subjects aged 13-15 years without caries (DMFT = 0) and 541
      children with dental caries (DMFT >= 1) in permanent dentition were selected from
      the ELSPAC study. Genotype determination of the ENAM polymorphism (rs12640848)
      was based on the TaqMan method. RESULTS: No significant differences in the allele
      or genotype frequencies between the caries-free children and those affected by
      dental caries were observed in both primary and permanent dentitions.
      CONCLUSIONS: Lack of association between the ENAM polymorphism (rs12640848) and
      dental caries in Czech children was detected. CLINICAL RELEVANCE: Although ENAM
      is considered as a candidate gene for dental caries, the presence of the ENAM
      variant (rs12640848) cannot be used as a risk factor of this multifactorial
      disease in the Czech population.

PMID- 29185147
TI  - Predicting pituitary stalk position by in vivo visualization of the hypothalamo
      hypophyseal tract in craniopharyngioma using diffusion tensor imaging
      tractography.
AB  - The pituitary stalk (PS) is crucial to endocrine function and water-electrolyte
      equilibrium. Preservation of the PS during craniopharyngioma (CP) surgery is
      critical; however, in a pathological state, it is difficult to identify. The
      hypothalamo-hypophyseal tract (HHT) connects the hypothalamus and the posterior
      pituitary gland and projects through the PS. Thus, visualization of the HHT can
      help locate the PS. Preoperative visualization of the neural fasciculus has been
      widely achieved using diffusion tensor imaging (DTI) tractography. Therefore,
      this study evaluated the use of DTI tractography to identify and characterize the
      human HHT. We used DTI tractography to track the HHT in 10 patients with CP and
      compared the location of the tract with the intraoperative view of the PS in
      these patients. We successfully tracked the HHT in nine patients, indicating that
      delineating and quantifying the tracked HHT using this method is feasible. In
      addition, we found that the tract was consistent with the intraoperative view of
      the PS in seven out of eight patients (87.50%). Finally, we found that the mean
      number of tracts was 7.11 +/- 12.28, the mean fractional anisotropy (FA) was 0.11
      +/- 0.04, and the mean tract length was 24.22 +/- 9.39 mm. Taken together, our
      results demonstrate that the HHT can be visualized and characterized with DTI
      even in a clinical application, which may aid in preoperative identification of
      the PS. Characterization of the tracked HHT with this technique could also be
      used to advance our understanding of the HHT.

PMID- 29185149
TI  - Laparoscopic Treatment of Median Arcuate Ligament Syndrome: Analysis of Long-Term
      Outcomes and Predictive Factors.
AB  - BACKGROUND: Laparoscopic arcuate ligament release has been demonstrated a valid
      therapeutic option for arcuate ligament syndrome. Nevertheless, long-term follow
      up and predictive factors have not been described for this treatment. METHODS:
      Clinical and surgical data and short- and long-term outcomes together with the
      impact of the degree of stenosis of the celiac trunk were analyzed in 13
      consecutive patients who underwent laparoscopic arcuate ligament release between
      2001 and 2013. RESULTS: Thirteen patients (12 F/1 M) underwent surgery. The
      median age was 32 years old, and their mean body mass index was 20.7 (range 14.7
      25). The 13 patients presented with intense postprandial abdominal pain. Ten
      cases were associated with weight loss. The median duration of symptoms was 24
      months (range 2-240). Three patients presented symptoms associated with superior
      mesenteric artery syndrome. Median operative time was 120 min (range 90-240), and
      there were no conversions to open surgery. Median hospital stay was 3 days (range
      2-14). Over a median follow-up of 117 months (range 45-185), nine patients had
      excellent results although two required endovascular procedures at 70 and 24
      months after surgery. Four patients (30.7%) experienced poor outcomes. When we
      analyzed the impact of the degree of occlusion of the celiac trunk, we observed
      that in patients with severe occlusion (> 70%), better results were obtained,
      with complete resolution of symptoms in 71% of cases. CONCLUSION: Laparoscopic
      arcuate ligament release constitutes an excellent treatment for arcuate ligament
      syndrome. The degree of occlusion of the celiac trunk may be a factor predictive
      of long-term outcomes.

PMID- 29185148
TI  - Therapeutic prospects of microRNAs in cancer treatment through nanotechnology.
AB  - MicroRNAs (miRNAs) represent a new class of diagnostic and prognostic biomarker
      as well as new therapeutic targets in cancer therapy. miRNAs are gaining
      significant interest due to extensive advancements in knowledge since their
      discovery and, more recently, their translational application as therapeutic
      moieties and targets in the management of disease. miRNAs used in the treatment
      of cancer would position them as a new class of emerging therapeutic agents.
      Indeed, numerous candidate miRNAs have been identified as having therapeutic
      application in the treatment of cancer, but there is still much to learn about
      how to transform these into effective, patient-compliant, and targeted drug
      delivery systems. In this mini review, we discuss the utility and potential of
      nanotechnology in miRNA formulation and delivery with particular emphasis on
      cancer, including their role in conferring multidrug resistance and metastatic
      capacity. This review benefits both the formulation and biological scientists in
      understanding and exploring the new vistas of miRNA delivery using nanotechnology
      in the cancer clinically.

PMID- 29185150
TI  - Key Ingredients-Target Groups, Methods and Messages, and Evaluation-of Local
      Level, Public Interventions to Counter Stigma and Discrimination: A Lived
      Experience Informed Selective Narrative Literature Review.
AB  - A proliferation of recent literature provides substantial direction as to the key
      ingredients-target groups, messages and methods, and evaluation-of local-level,
      public interventions to counter stigma and discrimination. This paper provides a
      selective narrative review of that literature from the perspective or standpoint
      of anti-stigma experts with lived experience of mental distress, the key findings
      of which have been synthesised and presented in diagrammatic overviews
      (infographics). These are intended to guide providers in planning, delivering and
      evaluating lived experience-directed local-level, public interventions to counter
      stigma and discrimination in accord with current best practice.

PMID- 29185151
TI  - The Use of Access Groups for Engagement in Community Mental Health Post
      Hospitalization.
AB  - This paper describes a novel approach to engaging psychiatric patients in care
      after discharge from inpatient or ER treatment. The Access Group model provides
      rapid, flexible, high-volume intake for up to 20 patient referrals per day.
      Patients are scheduled for intake by referring hospital clinicians using an
      online scheduling software and can be seen within 1-3 days of hospital discharge.
      Access allows flexibility, easy rescheduling, and limited wait time. At intake,
      patients and family members participate in a structured group intake procedure
      from which they are scheduled for follow-up psychiatry, therapy, and social work
      appointments. Same-day appointments are available for urgent needs. Initial
      evidence suggests that the Access Group model is effective at providing rapid
      access to and engagement in care, and is acceptable to patients. Generalizability
      and funding approaches for the model are discussed.

PMID- 29185152
TI  - Mental Health in China: Stigma, Family Obligations, and the Potential of Peer
      Support.
AB  - Some people with mental illness in China do not receive treatment. We explored
      how stigma and familial obligation influenced accessibility of social support for
      patients with depression in China and the potential acceptability of peer support
      programs. Semi-structured qualitative interviews were conducted with five
      psychiatrists and 16 patients receiving care for depression from a large
      psychiatric hospital in Jining, Shandong Province of China. Patients with mental
      illness reported barriers that prevented them from (a) receiving treatment and
      (b) relying on informal social support from family members, including stigma,
      somatization, and community norms. Circumventing these barriers, peer support
      (i.e., support from others with depression) was viewed by patients as an
      acceptable means of exchanging information and relying on others for support.
      Formative research on peer support programs to examine programming and activities
      may help reduce the burden of unmet mental health care needs in China.

PMID- 29185153
TI  - A Doctor is in the House: Stakeholder Focus Groups About Expanded Scope of
      Practice of Community Psychiatrists.
AB  - We sought to understand stakeholder perspectives on barriers to metabolic
      screening for people with severe mental illness. We additionally assessed the
      feasibility of expanding psychiatrists' scope of practice to include treatment of
      cardiometabolic abnormalities. We conducted four focus groups among patients with
      severe mental illness, community psychiatrists, primary care providers, and
      public health administrators. Focus group transcripts were thematically analyzed.
      Three domains emerged: challenges with patient navigation of the complex health
      care system, problem list prioritization difficulties, and concern that treatment
      of cardiometabolic abnormalities were beyond the scope of practice of
      psychiatrists. Stakeholders agreed that navigating the health care system was
      challenging for this population and led to undertreatment of cardiometabolic risk
      factors. Expansion of psychiatrists' scope of practice within community mental
      health appears acceptable to patients and may be a mechanism to improve
      cardiometabolic care among people with severe mental illness.

PMID- 29185154
TI  - Counseling on Access to Lethal Means (CALM): An Evaluation of a Suicide
      Prevention Means Restriction Training Program for Mental Health Providers.
AB  - This paper evaluates the effectiveness of the Counseling on Access to Lethal
      Means (CALM) suicide prevention program. CALM trains mental health providers how
      to counsel suicidal individuals and those who support them on mean restriction
      during times of crisis. Pre/post/3-month follow-up assessments measured knowledge
      of lethal means, confidence and comfort in discussing means restriction (self
      efficacy), and future intentions to counsel clients on means restriction. Change
      in the number of clients receiving lethal means counseling was also assessed. All
      constructs increased significantly at posttest. Confidence and counseling
      intentions were sustained at follow-up and significantly more clients received
      means counseling in the 3 months following the CALM training. Knowledge and
      comfort levels decreased at follow-up but not to pre-training levels. CALM is
      effective at increasing mental health professionals' comfort, knowledge, and
      frequency of talking about means restriction with clients. an effective means
      restriction training program. A template to assess clients for suicidality and
      lethal means access and booster sessions are recommended to further sustain
      effects.

PMID- 29185155
TI  - Successful treatment of follicular lymphoma with second-generation tyrosine
      kinase inhibitors administered for coexisting chronic myeloid leukemia.
AB  - Tyrosine kinase inhibitors (TKIs) are standard therapy for chronic myeloid
      leukemia (CML). However, the effects of these agents on mature B cell lymphoma
      are not well known. We describe a 50-year-old man who was diagnosed with CML in
      the chronic phase and treated with imatinib. After 3 years of imatinib therapy
      that achieved a complete cytogenetic response of CML, he developed Philadelphia
      negative follicular lymphoma (FL). Rituximab monotherapy induced a partial
      response of FL, and he subsequently achieved a major molecular response (MMR) of
      CML. Three years later, however, the MMR was lost, followed by the progression of
      FL. Imatinib was switched to nilotinib for the treatment of CML, while we chose
      watchful waiting for FL. He achieved MMR again under treatment with nilotinib for
      8 months including one month of substitutional use of dasatinib due to adverse
      events, but thereafter nilotinib was switched to bosutinib due to
      hyperbilirubinemia. With the administration of second-generation TKIs (2G-TKIs)
      for a total of 18 months, he achieved a complete response to FL without
      antilymphoma treatment. This is the first report to suggest that 2G-TKIs may have
      direct or indirect effects on FL.

PMID- 29185156
TI  - Hematopoietic stem cell transplantation for pulmonary alveolar proteinosis
      associated with primary immunodeficiency disease.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disorder that is characterized by
      the excessive accumulation of surfactant-like materials in the alveoli, leading
      to hypoxemic respiratory failure. We describe two Japanese infants with PAP
      associated with hypogammaglobulinemia and monocytopenia. These patients may have
      underlying primary immunodeficiency (PID) and were successfully treated with
      allogeneic hematopoietic stem cell transplantation (HSCT). This report indicates
      that allogeneic HSCT may provide a curative treatment for PAP associated with
      PID.

PMID- 29185157
TI  - Cell adhesion-induced phosphorylation and inactivation of EZH2 confer drug
      resistance to acute myeloid leukemia cells.

PMID- 29185158
TI  - Delivery of expression constructs of secreted frizzled-related protein 4 and its
      domains by chitosan-dextran sulfate nanoparticles enhances their expression and
      anti-cancer effects.
AB  - In malignant mesothelioma (MM) cells, secreted frizzled-related protein 4 (SFRP4)
      expression is downregulated by promoter methylation. In this study, we evaluated
      the effect of encapsulated chitosan-dextran (CS-DS) nanoparticle formulations of
      SFRP4 and its cysteine-rich domain (CRD) and netrin-like domain (NLD) as means of
      SFRP4-GFP protein delivery and their effects in JU77 and ONE58 MM cell lines. CS
      DS formulations of SFRP4, CRD, and NLD nanoparticles were prepared by a complex
      coacervation technique, and particle size ranged from 300 nm for empty particles
      to 337 nm for particles containing the proteins. Measurement of the zeta
      potential showed that all preparations were around 25 mV or above, suggesting
      stable formulation and good affinity for the DNA molecules. The CS-DS
      nanoparticle formulation maintained high integrity and entrapment efficiency.
      Gene delivery of SFRP4 and its domains showed enhanced biological effects in both
      JU77 and ONE58 cell lines when compared to the non-liposomal FUGENE(r) HD
      transfection reagent. In comparison to the CRD nanoparticles, both the SFRP4 and
      NLD nanoparticles significantly reduced the viability of MM cells, with the NLD
      showing the greatest effect. The CS-DS nanoparticle effects were observed at an
      earlier time point and with lower DNA concentrations. Morphological changes in MM
      cells were characterized by the formation of membrane-associated vesicles and
      green fluorescent protein expression specific to SFRP4 and the NLD. The findings
      from our proof-of-concept study provide a stepping stone for further
      investigations using in vivo models.

PMID- 29185159
TI  - The effect of estradiol, testosterone, and human chorionic gonadotropin on the
      proliferation of Schwann cells with NF1 +/- or NF1 -/- genotype derived from
      human cutaneous neurofibromas.
AB  - Dermal neurofibromas are the hallmarks of neurofibromatosis type 1 (NF1).
      Neurofibromas harbor Schwann cells with two different genotypes: Schwann cells
      which carry the germline mutation and a healthy NF1 allele (NF1 +/-), and a
      subpopulation of Schwann cells which harbor the so-called second hit leading to
      inactivation of both NF1 alleles (NF1 -/-). The second hit in the NF1 gene of
      Schwann cells is considered to be the initial step in the development of
      neurofibromas. Dermal neurofibromas typically start to grow in puberty, and their
      number and size increase during pregnancy, indicating hormone responsiveness.
      This is the first study to address the effect of human chorionic gonadotropin
      (hCG) on the proliferation of human NF1 +/- and NF1 -/- Schwann cells in vitro.
      In addition, the effects of estradiol and testosterone were also investigated.
      The results showed that NF1 -/- Schwann cells were more sensitive to estradiol,
      testosterone, and human chorionic gonadotropin than NF1 +/- cells. Specifically,
      the proliferation of NF1 -/- Schwann cells was increased by up to 99, 110, and
      170% compared to vehicle control when treated with estradiol, testosterone, and
      hCG, respectively. Interestingly, no effect of estradiol, testosterone, or hCG on
      the proliferation of the cells with NF1 +/- genotype was observed. To conclude,
      the somatic second hit in the NF1 gene sensitizes Schwann cells to sex hormones
      resulting in a highly increased proliferation. Our results highlight the
      significance of sex hormones in the regulation of neurofibroma growth.

PMID- 29185160
TI  - Exogenous growth factors enhance the expression of cola1, cola3, and Elastin in
      fibroblasts via activating MAPK signaling pathway.
AB  - Exogenous growth factors could accelerate the process of wound healing. However,
      the underlying mechanisms have not been clearly clarified. The aim of the present
      study was to investigate the effect of epidermal growth factor (EGF) and basic
      fibroblast growth factor (bFGF) on the expression of type I collagen (cola1),
      type III collagen (cola3), and Elastin in fibroblasts, which are widely expressed
      in fibroblasts and promote the function of fibroblasts. We measured the levels of
      cola1 and cola3 in human fibroblast cells cultured in medium containing EGF or
      bFGF at concentrations ranging from 0.1 to 1000 MUg/L by Western blotting and RT
      PCR assays, and found that EGF or bFGF enhanced the expression of cola1 and cola3
      in a concentration-dependent manner. We further discovered that after stimulation
      with EGF or bFGF in human fibroblast cells, mitogen-activated protein kinases
      (MAPK) family members were generally activated, whose expression trend was
      consistent with that of cola1, cola3, and Elastin. In summary, in this study, we
      uncovered that exogenous growth factors enhance the expression of cola1, cola3,
      and Elastin, which is probably regulated via activating MAPK signaling pathway.

PMID- 29185161
TI  - Exercise therapy and autonomic function in heart failure patients: a systematic
      review and meta-analysis.
AB  - A large body of evidence exists indicating that autonomic imbalance is
      characteristic of heart failure, with several parameters of autonomic function
      associated with adverse clinical outcomes. The aim of this systematic review and
      meta-analysis was to investigate the effects of exercise training on parameters
      of autonomic function in patients with heart failure and where possible quantify
      the size of the effect. We conducted database searches (PubMed, EMBASE and
      Cochrane Trials Register to 31 March 2017) for exercise-based rehabilitation
      trials in heart failure; using search terms, exercise training, autonomic
      function, heart rate recovery, heart rate variability and muscle sympathetic
      nerve activity. Pooled data indicated a statistically significant increase in
      heart rate recovery at 1 min (HRR1) in exercise compared to control groups, mean
      difference 5.90 bpm (95%CI 5.12, 6.69; p < 0.00001). Pooled data also indicated
      that exercise training improved the short-term heart rate variability (HRV)
      parameters of root mean square of successive differences between normal heart
      beats (RMSSD (ms)) [mean difference 10.44 (95%CI 0.60, 20.28, p = 0.04)] and high
      frequency normalised units (HFnu) [mean difference 7.72 (95%CI 3.32, 12.12, p =
      0.0006), which are predominantly reflective of parasympathetic activity. Analyses
      also indicated a statistically significant decrease in muscle sympathetic nerve
      activity (MSNA) bursts/minute (mean difference - 11.09 (95%CI - 16.18, - 6.00; p
      < 0.0001) and MSNA bursts/100 heart beats (mean difference - 15.44 (95%CI -
      20.95, -9.92; p < 0.00001) in exercise groups compared to controls. With
      improvements in HRR, HRV and MSNA, exercise training appears to facilitate an
      improvement in parasympathetic tone and reduction in sympathetic activity.

PMID- 29185162
TI  - The effect of Medicaid payer status on patient outcomes following repair of
      massive rotator cuff tears.
AB  - BACKGROUND: The influence of socioeconomic status and insurance type has not been
      studied extensively for RCR, particularly not in the high risk massive RCT
      population. The purpose of this study is to identify relationships between
      Medicaid payer status and patient outcomes following massive RCR. METHODS: A
      retrospective review of shoulder surgery database identified 29 patients
      undergoing massive rotator cuff repair. Patients were stratified based on
      insurance type into two cohorts, Medicaid (14 patients) and non-Medicaid (15
      patients). Missed routine follow-up appointments and comorbidities were recorded
      and compared between groups. Group comparisons were made for pre- and
      postoperative patient-reported and functional outcomes. Outcome scores included
      American Shoulder and Elbow Shoulder Score (ASES), the Penn Shoulder Score, and
      the Subjective Shoulder Value (SSV). A p value of < 0.05 was considered
      significant for all statistical analyses. RESULTS: Medicaid patients were on
      average 7.1 years younger than non-Medicaid patients (49.8 vs. 56.9 years,
      respectively), and remaining demographics were comparable between groups.
      Preoperative patient-reported outcomes were only significantly different for ASES
      and ASES pain (p = 0.010, 0.037). There was excellent average improvement for
      Medicaid patients but no significant differences compared to non-Medicaid
      patients for ASES (p = 0.630), PENN scores (p = 0.395), and SSV (p = 0.198).
      Medicaid patients also had a higher number of missed and canceled appointments
      (28%) compared to non-Medicaid patients (18%). CONCLUSION: Medicaid coverage will
      expand to millions of uninsured Americans under current healthcare reform.
      Medicaid patients with massive RCT appear to significantly improve with surgical
      treatment.

PMID- 29185163
TI  - Cardiopulmonary bypass for pediatric cardiac surgery.
AB  - The management of cardiopulmonary bypass for pediatric cardiac surgery is more
      challenging than that in adults due to the smaller size, immaturity, and
      complexity of the anatomy in children. Despite major improvements in
      cardiopulmonary bypass, there remain many subjects of debate. This review article
      discusses the physiology of cardiopulmonary bypass for pediatric and congenital
      heart surgery, including topics related to hemodilution, hypothermia, acid-base
      strategies, inflammatory response, and myocardial protection.

PMID- 29185164
TI  - Extracellular chromone derivatives in cell cultures of Pimpinella anisum.
      Influence of elicitation with methyl jasmonate and 2beta-methyl cyclodextrins.
AB  - OBJECTIVES: To explore the potentiality of undifferentiated Pimpinella anisum L.
      cell cultures for the production of secondary metabolites by means of
      elicitation. RESULTS: Two chromone compounds were secreted to the medium of
      undifferentiated cultures of P. anisum: 4-methoxyfuro[3,2-g]chromen-7-one, known
      as bergapten, which is constitutive to anise, and 5-hydroxy-7-methoxy-2
      methylchromen-4-one, the rare chromone eugenin, not yet described in P. anisum.
      Caffeoyl quinic acid species were also identified in the biomass. Elicitation
      with methyl jasmonate enhanced chromone accumulation in the medium and stimulated
      phenolic acid metabolism in the biomass (11 mg caffeoyl quinic acids g-1 DW
      cells). The application of 2,6-dimethyl-beta-cyclodextrins to cultures led to an
      intense accumulation of chromones, with nearly 10 mg l-1 bergapten and 150 mg l-1
      eugenin being accumulated extracellularly after optimal elicitation conditions.
      CONCLUSIONS: The significant amounts of eugenin obtained in the anise cultures
      and the stability of production over long periods of time can be of interest for
      its biotechnological production and for future studies on biosynthesis
      regulation.

PMID- 29185165
TI  - Immune parameters associated with mortality in the elderly are context-dependent:
      lessons from Sweden, Holland and Belgium.
AB  - The pioneering Swedish OCTO/NONA-Immune longitudinal studies led by Anders Wikby
      in Jonkoping in the 1990s established a cluster of simple baseline immune
      parameters associated with excess mortality in 85 year-old non-institutionalized
      individuals over 2, 4 and 6-year follow-up. We dubbed this cluster the "Immune
      Risk Profile" (IRP) consisting of poor proliferative responses of peripheral
      blood mononuclear cells to T cell mitogens, accumulations of CD8+ CD28- T-cells
      resulting in an inverted CD4:8 ratio, decreased amounts of B-cells, and
      seropositivity for Cytomegalovirus (CMV). The concept of the IRP has since been
      applied by others to many different populations in different circumstances and at
      different ages, but in general without specifically establishing whether the same
      risk factors were relevant in the tested subjects. However, our own later studies
      showed that risk factors in aged populations from The Netherlands and Belgium
      were markedly different, indicating that the IRP cannot simply be transferred
      between populations. Moreover, there was a striking sex difference in the Belgian
      study, which was the only one large enough to include sufficient numbers of old
      men. The reasons for these marked differences between populations which one might
      have assumed a priori to be quite similar to one another are not clear, and many
      candidates can be speculated upon, but the important lesson is that there is a
      marked context-dependency of immune biomarkers of ageing, suggesting that IRPs
      cannot be assumed to be identical in different populations.

PMID- 29185166
TI  - Echinacoside, a phenylethanoid glycoside from Cistanche deserticola, extends
      lifespan of Caenorhabditis elegans and protects from Abeta-induced toxicity.
AB  - Cistanche deserticola has been found to exert protection against aging and age
      related diseases, but mechanisms underlying its longevity effects remain largely
      unclear. Here, the multicellular model organism Caenorhabditis elegans was
      employed to identify lifespan extending and protective effects against beta
      amyloid (Abeta) induced toxicity by echinacoside (ECH), a phenylethanoid
      glycoside isolated from C. deserticola. Our results showed that ECH extends the
      mean lifespan of worms and increases their survival under oxidative stress.
      Levels of intracellular reactive oxygen species and fat accumulation were also
      significantly suppressed by ECH. Moreover, ECH-mediated lifespan extension was
      found to be dependent on mev-1, eat-2, daf-2, and daf-16, but not sir-2.1 or hsf
      1 genes. Furthermore, ECH triggered DAF-16 nuclear localization and upregulated
      two of its downstream targets, sod-3 and hsp-16.2. In addition, ECH significantly
      improved the survival of CL4176 worms in response to proteotoxic stress induced
      by Abeta protein aggregation. Collectively, these findings suggested that
      reactive oxygen species scavenging, dietary restriction, and insulin/insulin-like
      growth factor signaling pathways could be partly involved in ECH-mediated
      lifespan extension. Thus, ECH may target multiple longevity mechanisms to extend
      lifespan and have a potency to prevent Alzheimer's disease progression.

PMID- 29185167
TI  - Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder:
      Systematic Review and Meta-Analysis.
AB  - Association of congenital cytomegalovirus (CMV) infection with autism spectral
      disorder (ASD) has been suggested since 1980s. Despite the observed association,
      its role as a risk factor for ASD remains to be defined. In the present review,
      we systematically evaluated the available evidence associating congenital CMV
      infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase
      databases. Any studies on children with CMV infection and ASD were evaluated for
      eligibility and three observational studies were included in meta-analysis.
      Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31,
      95% CI 3.07-41.66) was indicated, too few events (0-2 events) in all included
      studies imposed serious limitations. There is urgent need for further studies to
      clarify this issue.

PMID- 29185168
TI  - Trans-splenic Embolization Plus Partial Splenic Embolization for Management of
      Variceal Bleeding Due to Left-Sided Portal Hypertension.

PMID- 29185169
TI  - How predictive are sex and empathizing-systemizing cognitive style for entry into
      the academic areas of social or physical sciences?
AB  - Based on the Empathizing-Systemizing (E-S) theory, it was hypothesized that the
      underrepresentation of female students in the physical sciences and the
      underrepresentation of males in the social sciences relates to differences in E-S
      cognitive style between the sexes. This hypothesis was tested in 115 physical
      science students and 155 social science students from a university in the
      Netherlands. The students completed visuospatial tests and the systemizing
      quotient-revised (SQ-R) as measures for systemizing, and a Cartoon Prediction
      test and the empathy quotient (EQ) as measures for empathizing. Independent of
      sex, the physical science students scored significantly lower than social science
      students on EQ (with large effect size) and 'brain type' that represents the
      standardized difference score between EQ and SQ-R (with large effect size).
      Physical science students, furthermore, scored significantly higher on the
      Cartoon Prediction task and one of the visuospatial tasks; however, these effects
      were only small of size. Unlike the scores on the SQ-R and the performance tests,
      the 'brain type' score of the EQ and SQ-R questionnaires was a good predictor of
      entry into social or physical sciences. Interestingly, the typical sex
      differences in more empathizing and less systemizing in females compared to males
      were only small for EQ and 'brain type', and absent for the SQ-R and the
      performance tests. This study only partially confirms the E-S theory, because
      typical sex differences were only minor in this selective sample and only the
      self-report measures predicted academic area in the absence of a role for sex.

PMID- 29185171
TI  - Effect of Xylan Sulfates on Coagulation of Human Blood Plasma.
AB  - Sulfated derivatives of xylan (isolated from Betula pubescens wood) with average
      molecular weight ~34 kDa, sulfur content of 11.3-17.5%, a degree of substitution
      of 0.74-1.64 are anticoagulants of direct type of action. Antithrombin and
      antifactor Xa activities in three tested xylan samples did not differ and reached
      30.8-31.8 and 13.5-14.3 U/mg, respectively.

PMID- 29185172
TI  - Correction to: Effects of nicomethanol hydrofluoride on dental enamel and
      synthetic apatites: a role for anti-caries protection.
AB  - The author of the article "Effects of nicomethanol hydrofluoride on dental enamel
      and synthetic apatites: a role for anti-caries protection", N. Sharkov, requested
      open access publication but owing to an error by the publisher the article was
      published electronically on the publisher's internet portal (currently
      SpringerLink) on 4 November 2017 without open access.

PMID- 29185170
TI  - Influence of time-of-day on joint Navon effect.
AB  - The shared attention theory suggests that people devote greater cognitive
      resources to those features co-attended simultaneously with others, determining
      better performance in several types of tasks. When co-actors performed a go/no-go
      Navon task attending different features of target letters, the performance was
      impaired, reflecting a joint Navon effect (the representation of a co-actor's
      attentional focus made it more difficult to select and apply one's own focus of
      attention), probably due to asynchronous co-attention with a decrease in
      cognitive resources involved. Researches in chronobiology and chronopsychology
      demonstrated that not only selective attention (involved in a Navon task), but
      also cognitive resources have a daily fluctuations, mainly paralleling the
      circadian rhythm of body temperature (i.e. increasing values from the morning to
      evening with a subsequent decline in the night). The study was conducted to
      assess whether the presence of joint attention, as measured by the joint Navon
      effect, was influenced by the time-of-day. Sixteen pairs of participants sitting
      next to each other were required to respond to the identity letters in a go/no-go
      Navon task twice: in the morning (09:00-10:00) and early afternoon (13:00-14:00).
      The results showed a joint Navon effect in the morning session only, suggesting
      that joint attention was affected by the time-of-day effect on cognitive
      resources.

PMID- 29185173
TI  - Increasing Prevalence of Alcohol Use Disorders: Meeting the Challenge in Primary
      Care : Commentary on Williams et al., Barriers to and Facilitators of Alcohol Use
      Disorder Pharmacotherapy in Primary Care: A Qualitative Study in Five VA Clinics.

PMID- 29185175
TI  - Pivot and Cluster: An Exercise in Clinical Reasoning.

PMID- 29185174
TI  - Physical, Psychological, Social, and Existential Symptoms in Older Homeless
      Experienced Adults: An Observational Study of the Hope Home Cohort.
AB  - BACKGROUND: The homeless population in the United States is aging. Aging
      associated comorbidities are associated with increased symptoms. OBJECTIVE: To
      describe the prevalence of symptoms among older homeless-experienced adults,
      analyze factors associated with moderate-high physical symptom burden, and
      identify symptom clusters. DESIGN: Cross-sectional analysis within longitudinal
      cohort study. PARTICIPANTS: Using population-based sampling from shelters, meal
      programs, encampments, and a recycling center in Oakland, CA, we recruited
      homeless adults aged >= 50 for a longitudinal cohort. This study includes
      participants who participated in the 18-month follow-up visit. MAIN MEASURES: We
      assessed physical symptoms using the Patient Health Questionnaire-15 (PHQ-15);
      psychological symptoms using the Center for Epidemiologic Studies Depression
      Scale (CES-D), Primary Care PTSD Screen (PC-PTSD), and psychiatric section of the
      Addiction Severity Index (ASI); loneliness using the Three-Item Loneliness Scale;
      and regret using a six-item regret scale. KEY RESULTS: Two hundred eighty-three
      participants (75.6% men and 82.3% African-Americans) completed symptoms
      interviews. Over a third (34.0%) had moderate-high physical symptom burden. The
      most prevalent physical symptoms were joint pain, fatigue, back pain, and sleep
      trouble. Over half (57.6%) had psychological symptoms; 39.6% exhibited loneliness
      and 26.5% had high regret. In a multivariate model, being a woman (AOR 2.54, 95%
      CI 1.28-5.03), childhood abuse (AOR 1.88, 95% CI 1.00-3.50), cannabis use (AOR
      2.59, 95% CI 1.38-4.89), multimorbidity (AOR 2.50, 95% CI 1.36-4.58), anxiety
      (AOR 4.30, 95% CI 2.24-8.26), hallucinations (AOR 3.77, 95% CI 1.36-10.43), and
      loneliness (AOR 2.32, 95% CI 1.26-4.28) were associated with moderate-high
      physical symptom burden. We identified four symptom clusters: minimal overall (n
      = 129), moderate overall (n = 68), high physical and high psychological (n = 67),
      and high physical and low psychological (n = 17). CONCLUSIONS: Older homeless
      experienced adults exhibit a high prevalence of symptoms across multiple
      dimensions. To reduce suffering, clinicians should recognize the interaction
      between symptoms and address multiple symptom dimensions.

PMID- 29185176
TI  - Communication Quality Predicts Psychological Well-Being and Satisfaction in
      Family Surrogates of Hospitalized Older Adults: An Observational Study.
AB  - BACKGROUND: Many hospitalized older adults require family surrogates to make
      decisions, but surrogates may perceive that the quality of medical decisions is
      low and may have poor psychological outcomes after the patient's hospitalization.
      OBJECTIVE: To determine the relationship between communication quality and high
      quality medical decisions, psychological well-being, and satisfaction for
      surrogates of hospitalized older adults. DESIGN: Observational study at three
      hospitals in a Midwest metropolitan area. PARTICIPANTS: Hospitalized older adults
      (65+ years) admitted to medicine and medical intensive care units who were unable
      to make medical decisions, and their family surrogates. Among 799 eligible dyads,
      364 (45.6%) completed the study. MAIN MEASURES: Communication was assessed during
      hospitalization using the information and emotional support subscales of the
      Family Inpatient Communication Survey. Decision quality was assessed with the
      Decisional Conflict Scale. Outcomes assessed at baseline and 4-6 weeks post
      discharge included anxiety (Generalized Anxiety Disorder-7), depression (Patient
      Health Questionnaire-9), post-traumatic stress (Impact of Event Scale-Revised),
      and satisfaction (Hospital Consumer Assessment of Healthcare Providers and
      Systems). KEY RESULTS: The mean patient age was 81.9 years (SD 8.32); 62% were
      women, and 28% African American. Among surrogates, 67% were adult children. Six
      to eight weeks post-discharge, 22.6% of surrogates reported anxiety (11.3%
      moderate-severe anxiety); 29% reported depression, (14.0% moderate-severe), and
      14.6% had high levels of post-traumatic stress. Emotional support was associated
      with lower odds of anxiety (adjusted odds ratio [AOR] = 0.65, 95% CI 0.50, 0.85)
      and depression (AOR = 0.80, 95% CI 0.65, 0.99) at follow-up. In multivariable
      linear regression, emotional support was associated with lower post-traumatic
      stress (beta = -0.30, p = 0.003) and higher decision quality (beta = -0.44, p <
      0.0001). Information was associated with higher post-traumatic stress (beta =
      0.23, p = 0.022) but also higher satisfaction (beta = 0.61, p < 0.001).
      CONCLUSIONS: Emotional support of hospital surrogates is consistently associated
      with better psychological outcomes and decision quality, suggesting an
      opportunity to improve decision making and well-being.

PMID- 29185177
TI  - An investigation of survivorship clinic attendance among childhood cancer
      survivors living in a five-state rural region.
AB  - PURPOSE: Cancer survivorship clinics manage cancer-related health complications
      and are available primarily in urban areas. We examine how demographic, clinical,
      and geographic-based characteristics are associated with attendance at the only
      pediatric survivorship clinic in a largely rural, multistate region. METHODS: One
      thousand eight hundred sixteen cancer survivors were diagnosed at age <= 25 from
      1986 to 2005 while living in the region. Cox models incorporating death as a
      competing risk and generalized estimating equations calculated hazards ratios
      (HR) for characteristics measured at the clinic's opening. Subjects were followed
      from the clinic opening their first visit, death, emigration from the catchment
      area, or December 31, 2014. RESULTS: Five percent of survivors visited the
      clinic. Attendance is positively associated with a leukemia or lymphoma diagnosis
      (HR = 3.32, 95% confidence interval [CI] = 1.72-6.78 vs CNS tumors), previous
      relapse (HR = 1.78, 95% CI = 1.00-3.19), and residing >100 mi from the clinic (HR
      = 2.05, 95% CI 1.03-4.10). Survivors aged >= 31 years at clinic opening (HR =
      0.19, 95% CI = 0.07-0.54) are less likely to attend than younger survivors.
      Residence between 16 and 100 mi had an inverse association with attendance,
      although not significant. CONCLUSION: Survivorship clinics are not widely
      attended by survivors in this catchment region. Efforts should be made to recruit
      survivors aged >= 31 and diagnosed with CNS tumors. Distance has a complex
      association with attendance, which could be attributed to the limited
      availability of preventative services in regions > 100 mi from the clinic.
      IMPLICATIONS FOR CANCER SURVIVORS: Survivors living in this catchment region may
      not be receiving care necessary to prevent severe late effects.

PMID- 29185178
TI  - Vasorelaxant activities and the underlying pharmacological mechanisms of Gynura
      procumbens Merr. leaf extracts on rat thoracic aorta.
AB  - Previous studies have investigated the cardiovascular activity of Gynura
      procumbens Merr. single-solvent extracts. The objective of this study was to
      evaluate the in vitro vasorelaxant properties and the underlying pharmacological
      mechanisms of serial extracts and fractions of Gynura procumbens (GP). The leaves
      of GP were serially extracted with petroleum ether, chloroform, methanol and
      water using the maceration method. Suspended aortic ring preparations were pre
      contracted with phenylephrine (PE 1 uM), followed by cumulative addition of GP
      extracts (0.25-3 mg/mL). The petroleum ether extract (GPPE) was the most potent
      among the four extracts. Pre-incubation of endothelium-intact aorta with atropine
      (1 uM), indomethacin (10 uM), methylene blue (10 uM), propranolol (1 uM) and
      potassium channel blockers such as TEA (1 uM), glibenclamide (10 uM), 4
      aminopyridine (1 uM) and barium chloride (10 mM) had no effect on GPPE-induced
      vasorelaxation. The vasorelaxant effect of GPPE was partly diminished by
      pretreatment of aortic rings preparations with L-NAME (10 uM) and even more so in
      endothelium-denuded aortic rings, indicating a minimal involvement of endothelium
      dependent pathway in GPPE-induced vasorelaxation. The calcium-induced
      vasocontractions were antagonized significantly and concentration-dependently by
      GPPE in calcium free and high potassium medium. These results illustrate that
      Ca2+ antagonizing actions of GPPE in rat isolated aorta are comparable to that of
      verapamil and may be mainly responsible for its vasodilation effect. The
      antioxidant activity of GPPE supports its vasorelaxant effect by attenuating the
      production of deleterious free radicals and reactive oxygen species in the
      vasculature.

PMID- 29185179
TI  - Enniatin B and ochratoxin A in the blood serum of workers from the waste
      management setting.
AB  - The waste management occupational environment is recognized by the simultaneous
      presence of several substances and biologic agents. Therefore, workers are
      exposed simultaneously to multiple contaminants. Occupational exposure to
      aflatoxin B1 in one Portuguese waste sorting plant was already reported. However,
      besides this mycotoxin, data regarding fungal contamination showed that exposure
      to other mycotoxins could be expected. A study was developed to analyze if
      exposure to other mycotoxins besides aflatoxin B1 was occurring in the workers
      from the waste sorting plant previously assessed and to discuss how these
      findings need to be considered in the risk assessment process. In addition to
      aflatoxin B1 detected previously by ELISA, two additional mycotoxins and one
      mycotoxin degradation product were detected and quantified by a multi-mycotoxin
      HPLC-MS/MS approach: Enniatin B and ochratoxin A as well as 2'R-ochratoxin A.
      Besides the confirmation of co-exposure to several mycotoxins, results probably
      indicate different exposure routes for the mycotoxins reported.

PMID- 29185181
TI  - Efficacy and safety of transcatheter aortic valve implantation with Edwards
      SAPIEN 3 and XT in smaller Asian anatomy.
AB  - We aimed to compare the efficacy and safety of transcatheter aortic valve
      implantation (TAVI) using Edwards SAPIEN 3 (S3) valve and SAPIEN XT) in smaller
      anatomy. The new generation S3 TAVI device has been used worldwide; however, its
      efficacy and safety in smaller Asian anatomy remain unknown. Between February
      2014 and March 2017, 166 consecutive patients (S3, 54; XT, 112) were treated with
      balloon-expandable TAVI in a single center and their outcomes were analyzed.
      Median patient age was 85 (range: 81-88) years and mean body surface area was
      1.41 +/- 0.15 m2. A 23-mm size valve was used in S3 and XT groups (70 vs. 62%, p
      = 0.224). The transfemoral approach was more frequently used in the S3 than in
      the XT group (96 vs. 72%, p < 0.001). Although, the minimal luminal diameter of
      the femoral artery was smaller in the S3 group (5.9 vs. 6.4 mm, p = 0.001), the
      rates of major (2 vs. 11%, p = 0.226) and minor (11 vs. 5%, p = 0.107) vascular
      complications did not increase. The frequency of paravalvular leaks (PVL) >= 2
      was significantly reduced in the S3 group (11 vs. 61%, p < 0.001); however, pre-
      (24 vs. 91%, p < 0.001) and post- (4 vs. 19%, p < 0.001) dilatations were less
      frequently performed. Pacemaker implantation incidence did not increase (4 vs.
      5%, p = 1.0) and peak velocity of the transcatheter heart valve was significantly
      higher in the S3 group (2.3 vs. 2.2 m/s, p = 0.046). Device success was high (89
      vs. 93%, p = 0.387) while the 30-day all-cause mortality was low (2 vs. 1%, p =
      0.583) in both groups. TAVI with the S3 device was safe and effective, with low
      incidence of vascular complications and reduced PVL, in smaller body-sized
      Asians.

PMID- 29185180
TI  - Subtype Specification of Cerebral Cortical Neurons in Their Immature Stages.
AB  - The diversification of neuronal subtypes during corticogenesis is fundamental to
      the establishment of the complex cortical structure. Although subtype
      specification has been assumed to occur in neural progenitor cells, increasing
      evidence has begun to reveal the plasticity of subtype determination in immature
      neurons. Here, we summarize recent findings regarding the regulation of subtype
      specification during later periods of neuronal differentiation, such as the post
      mitotic and post-migratory stages. We also discuss thalamocortical axons as an
      extra-cortical cue that provides information on the subtype determination of
      immature cortical neurons.

PMID- 29185183
TI  - Nuclear cardiology and ASNC: The case for optimism.

PMID- 29185182
TI  - Tinnitus, Traumatic Brain Injury, and Posttraumatic Stress Disorder in the
      Military.
AB  - PURPOSE: Acoustic trauma is more prevalent in military settings, especially among
      individuals with combat-related military occupational specialties. Gunfire,
      improvised explosive devices, and mortar explosions are a few examples that may
      cause hearing degradation and tinnitus. It is possible that the same events that
      are associated with auditory problems can cause traumatic brain injury (TBI) and
      posttraumatic stress disorder (PTSD). METHOD: This paper reviews the distinct and
      overlapping symptoms of tinnitus, TBI, and PTSD, and how these disorders interact
      to synergistically promote negative outcomes. RESULTS: Tinnitus may serve as a
      significant contributor to symptoms of TBI and PTSD. Therefore, tinnitus subtypes
      could be identified as physiologically or psychologically based, or both.
      CONCLUSIONS: Additional research is warranted to determine the common and unique
      symptoms and associated neurological pathways of tinnitus, TBI, and PTSD. Brief
      treatment recommendations are provided, including a multidisciplinary approach
      for the physical and psychological distress associated with tinnitus.

PMID- 29185184
TI  - Changes in contractile and metabolic parameters of skeletal muscle as rats age
      from 3 to 12 months.
AB  - Laboratory rats are considered mature at 3 months despite that musculoskeletal
      growth is still occurring. Changes in muscle physiological and biochemical
      characteristics during development from 3 months, however, are not well
      understood. Whole muscles and single skinned fibres from fast-twitch extensor
      digitorum longus (EDL) and predominantly slow-twitch soleus (SOL) muscles were
      examined from male Sprague-Dawley rats (3, 6, 9, 12 months). Ca2+ sensitivity of
      contractile apparatus decreased with age in both fast- (~ 0.04 pCa units) and
      slow-twitch (~ 0.07 pCa units) muscle fibres, and specific force increased (by ~
      50% and ~ 25%, respectively). Myosin heavy chain composition of EDL and SOL
      muscles altered to a small extent with age (decrease in MHCIIa proportion after 3
      months). Glycogen content increased with age (~ 80% in EDL and 25% in SOL) and
      GLUT4 protein density decreased (~ 35 and 20%, respectively), whereas the
      glycogen-related enzymes were little changed. GAPDH protein content was
      relatively constant in both muscle types, but COXIV protein decreased ~ 40% in
      SOL muscle. Calsequestrin (CSQ) and SERCA densities remained relatively constant
      with age, whereas there was a progressive ~ 2-3 fold increase in CSQ-like
      proteins, though their role and importance remain unclear. There was also ~ 40%
      decrease in the density of the Na+, K+-ATPase (NKA) alpha1 subunit in EDL and the
      alpha2 subunit in SOL. These findings emphasise there are substantial changes in
      skeletal muscle function and the density of key proteins during early to mid
      adulthood in rats, which need to be considered in the design and interpretation
      of experiments.

PMID- 29185185
TI  - The Long-Term Effects of the Adjustable Gastric Band on Esophageal Motility in
      Patients Who Present for Band Removal.
AB  - BACKGROUND: During the past decade, laparoscopic adjustable gastric banding
      (LAGB) was one of the most popular surgical procedures in treating morbid
      obesity. Long-term effects, specifically on esophageal motility, of LAGB have not
      been well described in the literature despite the high prevalence of reoperations
      and post-operative dysphagia. We aimed to characterize esophageal dysmotility
      after long-term follow-up using data of high-resolution esophageal manometry
      (HRM) performed in patients who presented for LAGB removal. The research was
      conducted in Academic Hospital Center in the USA. METHODS: Research was conducted
      with approval from the institution's Institutional Review Board. We included 25
      consecutive patients who were requesting removal of the band or revisional
      bariatric surgery. All patients underwent HRM between 2011 and 2015. RESULTS: A
      Fisher's exact test two-sided p value 0.41 shows no statistically significant
      difference in proportions of normal motility or impaired motility between
      asymptomatic and symptomatic patients. CONCLUSIONS: Patients with a history of
      LABG can have esophageal dysmotility whether they are symptomatic or
      asymptomatic. Based on existing literature, we recommend pre-operative manometry
      in these patients requesting revisional surgery.

PMID- 29185186
TI  - Correction to: Gender difference in acquired seizure susceptibility in adult rats
      after early complex febrile seizures.
AB  - In the original publication of the article, the representative EEG of female rat
      pups with FS in Figure 1 C and D was incorrectly intercepted from that of male
      rat pups. This correction does not affect the conclusions of the paper. Figure 1
      has been corrected on the online PDF version and displayed below.

PMID- 29185188
TI  - Re: Should every medical student have exposure to robotic surgery?

PMID- 29185189
TI  - Dyeing of Polyester and Nylon with Semi-synthetic Azo Dye by Chemical
      Modification of Natural Source Areca Nut.
AB  - Various azo compounds (Modified dyes) have been synthesised by chemical
      modification of areca nut extract (epicatechin), a plant-based Polyphenolic
      compound to get semi-synthetic dyes. Three different primary amines namely p-
      nitro aniline, p-anisidine and aniline, were diazotized to form their
      corresponding diazonium salts which were further coupled with an areca nut
      extract. Preliminary characterization of the areca nut extract and the resultant
      azo compounds (Modified dyes) was carried out in terms of melting point,
      solubility tests, thin layer chromatography, UV-Visible and FTIR spectroscopy.
      These modified dyes were further applied on polyester and nylon fabrics and % dye
      exhaustion was evaluated. Dyed fabrics were further tested for their fastness
      properties such as wash fastness, rubbing fastness, light fastness and
      sublimation fastness. The results of the fastness tests indicate that, all the
      three modified dyes have good dyeability for polyester and nylon fabrics. The
      dyed fabrics were also tested for ultraviolet protection factor which showed very
      good ultraviolet protection.

PMID- 29185187
TI  - Extracellular Vesicle Biology in Alzheimer's Disease and Related Tauopathy.
AB  - Extracellular vesicles (EVs) are physiological vesicles secreted from most
      eukaryotes and contain cargos of their cell of origin. EVs, and particularly a
      subset of EV known as exosomes, are emerging as key mediators of cell to cell
      communication and waste management for cells both during normal organismal
      function and in disease. In this review, we investigate the rapidly growing field
      of exosome biology, their biogenesis, cargo loading, and uptake by other cells.
      We particularly consider the role of exosomes in Alzheimer's disease, both as a
      pathogenic agent and as a disease biomarker. We also explore the emerging role of
      exosomes in chronic traumatic encephalopathy. Finally, we highlight open
      questions in these fields and the possible use of exosomes as therapeutic targets
      and agents.

PMID- 29185190
TI  - Do Vascular Mural Cells Possess Endogenous Plasticity In Vivo?

PMID- 29185191
TI  - Delivery of Exogenous miR-124 to Glioblastoma Multiform Cells by Wharton's Jelly
      Mesenchymal Stem Cells Decreases Cell Proliferation and Migration, and Confers
      Chemosensitivity.
AB  - MicroRNAs (miRs) are potential therapeutic targets in glioblastoma multiforme
      (GBM), but the difficulties associated with their delivery to tumor target cells
      have hampered their widespread use. Mesenchymal stem cells (MSCs) can migrate to
      the sites of cancers, including GBM and exert anti-tumor effects. In this study,
      it is shown that Wharton's jelly-MSCs (WJ-MSCs) have the ability to deliver
      exogenous miRs to GBM cells and the functional impact of this delivery is
      characterized. It is found that the labeled miR-124, as an example for miR of
      interest, can be successfully delivered with WJ-MSCs to U87 GBM cells via
      dependent or exosome-independent processes. It is demonstrated that the delivered
      exogenous miR-124 significantly decreases the luciferase activity of the target
      gene CDK6. In addition, the delivered miR-124 enhances the chemosensitivity of
      GBM cells to temozolomide and decreases the migration of GBM cells. These results
      suggest that the use of exogenous miRNA delivery with the derived exosomes from
      WJ-MSCs may provide a novel approach for miRNA replacement therapy in GBM
      cancers.

PMID- 29185192
TI  - A Functional Aryl Hydrocarbon Receptor Genetic Variant, Alone and in Combination
      with Parental Exposure, is a Risk Factor for Congenital Heart Disease.
AB  - Recent experimental studies showed that ablation of the aryl hydrocarbon receptor
      (AhR) as well as its activation by exogenous ligands disrupt the molecular
      networks involved in heart formation and function, leading to congenital heart
      disease (CHD). However, no evidence is available about the role of AhR in humans.
      We assessed the prevalence of a functional AhR genetic variant (p.Arg554Lys) in
      CHD patients as well as its joint effects with parental exposure. A total of 128
      CHD patients (76 males; age 6.2 +/- 6.7 years) and 274 controls (160 males; age
      at birth) were genotyped for the AhR polymorphism by using the TaqMan(r) Drug
      Metabolism Genotyping assay. Both case and control parents completed a structured
      questionnaire on demographic, lifestyle and preconception exposures. Genotype (p
      = 0.001) and allele (p < 0.0001) distributions of AhR p.Arg554Lys differed
      significantly between patients and controls. A significant elevated CHD risk was
      found under dominant (OR = 2.9, 95% CI 1.9-4.6, p < 0.0001) and additive genetic
      models (OR = 6.2, 95% CI 2-19, p = 0.001). There was a significant interaction
      between 554-Lys allele and paternal smoking exposure (ORsmoking = 1.6, 95% CI =
      0.9-2.9; ORallele = 2.6, 95% CI = 1.3-5; ORinteraction = 4.9, 95% CI = 2.4-9.9, p
      interaction < 0.0001). Additionally, 554-Lys allele exacerbated the effect of
      maternal periconceptional exposure (ORexposure = 1.6, 95% CI = 0.8-3; ORallele =
      2.6, 95% CI = 1.5-4.5; ORinteraction = 5.7; 95% CI = 2.6-12, p interaction <
      0.0001). Our findings showed that the AhR p.Arg554Lys polymorphism, alone and in
      combination with parental exposures, is associated with the CHD risk,
      highlighting the significant role of AhR in the cardiovascular development.

PMID- 29185193
TI  - Physical exercise promotes memory capability by enhancing hippocampal
      mitochondrial functions and inhibiting apoptosis in obesity-induced insulin
      resistance by high fat diet.
AB  - A high-fat diet induces obesity in mice, leading to insulin resistance, decreased
      mitochondrial function, and increased apoptosis in the hippocampus, which
      eventually result in memory loss. The present study investigated the effect of
      physical exercise on memory, hippocampal mitochondrial function, and apoptosis in
      mice with in insulin resistance caused by obesity due to high-fat diet. Mice were
      randomly divided into four groups: control (CON), control and exercise (CON +
      EX), high fat diet (HFD), and high fat diet and exercise (HFD + EX). After
      receiving a high-fat (60%) diet for 20 weeks to induce obesity, the animals were
      subjected to an exercise routine 6 times per week, for 12 weeks. The exercise
      duration and intensity gradually increased over 4-week intervals. Hippocampal
      memory was examined using the step-down avoidance task. Mitochondrial function
      and apoptosis were also examined in the hippocampus and dentate gyrus. We found
      that obesity owing to a high-fat diet induced insulin resistance and caused a
      decrease in memory function. Insulin resistance also caused a decrease in
      mitochondrial function in the hippocampus by reducing Ca2+ retention and O2,
      respiration, increasing the levels of H2O2, and Cyp-D, and mPTP opening. In
      addition, apoptosis in the hippocampus increased owing to decreased expression of
      Bcl-2 and increased expression of Bax, cytochrome c, and caspase-3 and TUNEL
      positive cells. In contrast, physical exercise led to reduced insulin resistance,
      improved mitochondrial function, and reduced apoptosis in the hippocampus. The
      results suggest that physiological stimulations such as exercise improve
      hippocampal function and suppress apoptosis, potentially preventing the memory
      loss associated with obesity-induced insulin resistance.

PMID- 29185194
TI  - Author response to Kingston's comment on "An Increase in Dietary Supplement
      Exposures Reported to US Poison Control Centers".

PMID- 29185195
TI  - Comment on "An Increase in Dietary Supplement Exposures Reported to US Poison
      Control Centers".

PMID- 29185196
TI  - ACMT Position Statement: Addressing the Rising Cost of Prescription Antidotes.
AB  - Antidotal therapy is an essential component of poisoning management. In recent
      years, there have been unprecedented increases in the costs of antidotes. The
      American College of Medical Toxicology calls upon providers, hospitals,
      formularies pharmaceutical industry, government, insurance companies, and
      pharmacy benefit managers to adopt practices to ensure that antidotes are
      available to our patients and price are based on value and cost.

PMID- 29185197
TI  - A Non-Peptidic S100A9 Specific Ligand for Optical Imaging of Phagocyte Activity
      In Vivo.
AB  - PURPOSE: Non-invasive assessment of inflammatory activity in the course of
      various diseases is a largely unmet clinical challenge. An early feature of
      inflammation is local secretion of the alarmin S100A8/A9 by activated phagocytes.
      We here evaluate a novel S100A9-targeted small molecule tracer Cy5.5-CES271 for
      in vivo optical imaging of inflammatory activity in exemplary disease models.
      PROCEDURES: Dynamics of Cy5.5-CES271 was characterized in a model of irritant
      contact dermatitis by sequential fluorescence reflectance imaging (FRI) up to 24
      h postinjection (p.i.). Specificity of Cy5.5-CES271 binding to S100A9 in vivo was
      examined by blocking studies and by employing S100A9-/- mice. Finally, S100A9
      secretion in acute lung inflammation was assessed by Cy5.5-CES271 and FRI of
      explanted lungs. RESULTS: In ear inflammation, we were able to non-invasively
      follow the time course of S100A9 expression using Cy5.5-CES271 and FRI over 24 h
      p.i. (peak activity at 3 h p.i.). Specificity of imaging could be shown by a
      significant signal reduction after predosing and using S100A9-/- mice. In acute
      lung injury, local and systemic S100A8/A9 levels increased over time and
      correlated significantly with FRI signal levels in explanted lungs. CONCLUSIONS:
      Cy5.5-CES271 shows significant accumulation in models of inflammatory diseases
      and specific binding to S100A9 in vivo. This study, for the first time,
      demonstrates the potential of a small molecule non-peptidic tracer enabling
      imaging of S100A9 as a marker of local phagocyte activity in inflammatory
      scenarios suggesting this compound class for translational attempts.

PMID- 29185198
TI  - Metastatic renal cell carcinoma to the small bowel: three cases of GI bleeding
      and a literature review.
AB  - Approximately 25-30% of patients with renal cell carcinoma (RCC) have metastatic
      disease at the time of diagnosis, where the most common sites of metastasis are
      the lung (50-60% of patients with metastatic disease), bones (30-40%), liver (30
      40%), and brain (5%). Although RCC metastasis to the small intestine is thought
      to be exceedingly rare, with predominantly isolated case reports and a few case
      series in the literature, we present below three additional cases at our
      institution of metastatic RCC to the small bowel presenting as GI bleeding. A
      literature review demonstrates that the number of published case reports has been
      increasing in recent years. We hypothesize that in the era of targeted
      chemotherapy and VEGF inhibitors to treat RCC that patients are living longer and
      have more time for their primary tumors to metastasize to the small bowel and
      become symptomatic, causing metastatic RCC to the small bowel to be less rare
      than previously thought.

PMID- 29185199
TI  - Predictors for the Treatment Effect of Sodium Glucose Co-transporter 2 Inhibitors
      in Patients with Type 2 Diabetes Mellitus.
AB  - INTRODUCTION: Predictors for the effect of sodium glucose co-transporter 2
      (SGLT2) inhibitors at lowering hemoglobin A1c (HbA1c) levels in type 2 diabetes
      mellitus patients remain unclear. We therefore aimed to elucidate these
      predictors in type 2 diabetes patients after 3 months of SGLT2 treatment.
      METHODS: A total of 302 consecutive type 2 diabetes patients who had been treated
      with SGLT2 inhibitors as monotherapy or add-on therapy to existing antidiabetic
      treatments were enrolled retrospectively. After excluding 27 patients whose HbA1c
      levels could not be evaluated 3 months after treatment, the glucose-lowering
      effects of SGLT2 inhibitors were assessed in 275 patients by measuring HbA1c
      levels before and 3 months after treatment. The predictors for changes in HbA1c
      levels after 3 months of treatment were evaluated. RESULTS: SGLT2 inhibitor
      treatment for 3 months decreased HbA1c levels from 7.8 +/- 1.2% to 7.4 +/- 1.0%
      (p < 0.0001). A multiple regression analysis showed that the independent
      determinants for SGLT2 inhibitor treatment effect included decreased HbA1c levels
      after 1 month of treatment, high baseline HbA1c levels, and a high estimated
      glomerular filtration rate (eGFR). CONCLUSION: We show that type 2 diabetes
      patients who received the greatest glucose-lowering effect with SGLT2 inhibitor
      treatment were those with preserved renal function (high baseline eGFR) and high
      baseline HbA1c levels. Moreover, SGLT2 inhibitor treatment efficacy could be
      predicted by the patients' initial response to treatment.

PMID- 29185200
TI  - The MTHFR polymorphism affect the susceptibility of HCC and the prognosis of HCC
      liver transplantation.
AB  - BACKGROUND: Methylenetetrahyfrofolate reductase (MTHFR) is the key enzyme for one
      carbon and folate metabolism. Previous studies have drawn different conclusions
      about the relationship between the mutation of MTHFR and hepatocellular carcinoma
      (HCC) occurrence. MTHFR polymorphisms' influence on liver transplantation for HCC
      recurrence has yet not been reported. Aim of this study was to clarify the impact
      of MTHFR polymorphism on hepatocarcinogenesis and the prognosis of liver
      transplant recipient with HCC. METHODS: This study enrolled 244 HCC patients and
      487 healthy individuals in Chinese Han population to analyze the influence of
      MTHFR polymorphism on HCC susceptibility first. Furthermore, this research choose
      another 100 donors' and 104 recipients' specimens to detect the association
      between polymorphism of MTHFR and post-transplant HCC recurrence. RESULT:
      rs1801131 polymorphism A to C was associated with the occurrence of HCC in
      Chinese Han population (p < 0.05), especially in age exceeding 50 years (p <
      0.01). No association was observed with rs1801133 polymorphism and HCC
      occurrence. The mean tumor-free survival for recipients with donor liver graft
      rs1801133 C to T variants was shorter than CC type (12.63 +/- 3.84 vs 22.43 +/-
      4.74 months, p < 0.05). Multivariate analysis revealed that Donor rs1801133 and
      Hangzhou criteria were two independent prognostic factors for tumor-free survival
      (p < 0.05). Neither donor rs1801131 polymorphism nor recipients' MTHFR
      polymorphisms was associated with HCC recurrence. CONCLUSION: This study
      demonstrated that MTHFR polymorphism was associated with HCC occurrence and post
      transplant HCC recurrence. rs1801131 mutation A to C is a valuable molecular
      biomarker for predicting HCC occurrence in Chinese Han population. Donor MTHFR
      rs1801133 C to T polymorphism could present as a promising prognostic biomarkers
      for HCC recurrence in liver transplant recipients.

PMID- 29185201
TI  - Are training and transfer effects of working memory updating training modulated
      by achievement motivation?
AB  - Previous studies examining effects of working memory (WM) updating training
      revealed mixed results. One factor that might modulate training gains, and
      possibly also transfer of those gains to non-trained cognitive tasks, is
      achievement motivation. In the present Studies 1 and 2, students with either a
      high (HAM) or low (LAM) achievement motivation completed a 14-day visuospatial WM
      updating training program. In Study 2, the students also performed a set of tasks
      measuring other executive functions and fluid intelligence prior to and after
      training. In both studies, the HAM students displayed a larger training gain than
      the LAM students. Study 2 revealed that after training, both groups showed better
      performance on the near-transfer but not far-transfer tasks. Importantly, the
      differential training gain was not associated with better post-training
      performance for the HAM compared to the LAM students on any of the transfer
      tasks. These results are taken to support a modulatory role of achievement
      motivation on WM training benefits, but not on transfer of those benefits to
      other tasks. Possible reasons for the general improvement on the near-transfer
      tasks and the absence of a modulatory role of achievement motivation on transfer
      task performance are discussed.

PMID- 29185202
TI  - Tumor-infiltrating lymphocytes affect the efficacy of trastuzumab-based treatment
      in human epidermal growth factor receptor 2-positive breast cancer.
AB  - BACKGROUND: Immune responses play an important role in interrupting the
      progression of cancer cells. Tumor-infiltrating lymphocytes (TILs) are basic
      components of the immune system. In triple negative breast cancer, increased
      number of TILs is associated with excellent prognosis and response of
      chemotherapy. Here, we investigated whether TILs affect the efficacy of
      trastuzumab-based treatment in human epidermal growth factor receptor 2 (HER2)
      positive breast cancer. METHODS: The study included 97 patients with stage I-III
      HER2-positive breast cancer. All patients were preoperatively treated with an
      anthracycline-based combination regimen, followed by taxane with trastuzumab from
      2009 to 2013. Pathological complete response (pCR) was defined as the
      disappearance of invasive cancer cells regardless of the presence of in situ
      components. TILs were evaluated using pre-therapeutic needle biopsy specimens. We
      assessed the percentage of the breast stroma with TILs over the total
      intratumoral stroma and classified the specimens in three grades: TILs1+ < 30%,
      TILs2+ 30-50%, and TILs3+ > 50%. RESULTS: Overall, 80.4% of the specimens were
      TILs1+, 15.5% were TILs2+ and 4.1% were TILs3+. The pCR rate was 44.9% (35/78) in
      the TILs1+ cases, 80.0% (12/15) in the TILs2+ cases and 75.0% (3/4) in the TILs3+
      cases. TILs were significantly associated with pCR (P = 0.0228). Multivariate
      analysis using TILs, hormone receptor (HR), nuclear grade (NG) and age indicated
      that TILs (OR 4.32, 95% CI 1.04-23.33, P = 0.0436) and HR (OR 8.76, 95% CI 3.30
      25.44, P < 0.0001) were independent predictors for pCR. CONCLUSION: TILs are
      associated with the efficacy of trastuzumab-based treatment in HER2-positive
      breast cancer.

PMID- 29185203
TI  - Genetic Diversity Among Genogroup II Noroviruses and Progressive Emergence of
      GII.17 in Wastewaters in Italy (2011-2016) Revealed by Next-Generation and Sanger
      Sequencing.
AB  - Noroviruses (NoV) are a major cause of gastroenteritis worldwide. Recently, a
      novel variant of NoV GII.17 (GII.P17_GII.17 NoV), termed Kawasaki 2014, has been
      increasingly reported in NoV outbreaks in Asia, and has also been described in
      Europe and North America. In this study, sewage samples were investigated to
      study the occurrence and genetic diversity of NoV genogroup II (GII) along a 6
      year period. Moreover, the spread of GII.17 strains (first appearance and
      occurrence along time) was specifically assessed. A total of 122 sewage samples
      collected from 2011 to 2016 from four wastewater treatment plants in Rome (Italy)
      were initially tested using real-time RT-(q)PCR for GII NoV. Positive samples
      were subsequently subjected to genotypic characterization by RT-nested PCRs using
      broad-range primes targeting the region C of the capsid gene of GII NoV, and
      specific primers targeting the same region of GII.17 NoV. In total, eight
      different genotypes were detected with the broad-range assay: GII.1 (n = 6),
      GII.2 (n = 8), GII.3 (n = 3), GII.4 (n = 13), GII.6 (n = 3), GII.7 (n = 2),
      GII.13 (n = 2), and GII.17 (n = 3), with the latter two genotypes detected only
      in 2016. Specific amplification of GII.17 NoV was successful in 14 out of 110
      positive samples, spanned over the years 2013-2016. The amplicons of the broad
      range PCR, pooled per year, were further analyzed by next-generation sequencing
      (NGS) for a deeper analysis of the genotypes circulating in the study period. NGS
      confirmed the circulation of GII.17 NoV since 2013 and detected, beyond the eight
      genotypes identified by Sanger sequencing, three additional genotypes regarded as
      globally uncommon: GII.5, GII.16, and GII.21. This study provides evidence that
      GII.17 NoV Kawasaki has been circulating in the Italian population before its
      appearance and identification in clinical cases, and has become a major genotype
      in 2016. Our results confirm the usefulness of wastewater surveillance coupled
      with NGS to study the molecular epidemiology of NoV and to monitor the emergence
      of NoV strains.

PMID- 29185204
TI  - Impact of chronic obstructive pulmonary disease and frailty on long-term outcomes
      and quality of life after transcatheter aortic valve implantation.
AB  - BACKGROUND: Association between chronic obstructive pulmonary disease (COPD) and
      long-term mortality as well as the quality of life (QoL) in patients with severe
      aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) is
      still unclear. AIM: We sought to evaluate the impact of COPD on mortality and QoL
      of patients with AS undergoing TAVI. METHODS: A total of 148 consecutive patients
      who underwent TAVI were enrolled and stratified by history of COPD. RESULTS: Of
      148 patients enrolled, 19 (12.8%) patients had a history of COPD. Patients with
      COPD were high-risk patients with higher prevalence of incomplete
      revascularization and frailty features. At follow-up of 15.8 months, all-cause
      mortality in patients with COPD was over four times higher than in patients
      without COPD [17.8% vs. 52.6%; p = 0.002-age/gender-adjusted OR (95% CI) 4.73
      (1.69-13.24)]. On the other hand, in Cox regression model, the only independent
      predictors of all-cause death at long-term follow-up were: incomplete coronary
      revascularization [HR (95% CI) 5.45 (2.38-12.52); p = 0.001], estimated
      glomerular filtration rate [per 1 ml/min/1.73 m2 increase: 0.96 (0.94-0.98); p =
      0.001], and previous stroke/transient ischemic attack [2.86 (1.17-7.00); p =
      0.021]. Also, the difference in mortality between patients with and without COPD
      was not significant after adjustment for the most of frailty indices.
      Importantly, groups were comparable in terms of QoL at baseline and 12 months.
      CONCLUSION: COPD may pose an important factor affecting long-term outcomes of
      patients with severe AS undergoing TAVI. However, its effects might be partially
      related to coexisting comorbidities and frailty.

PMID- 29185205
TI  - I and Us: A Longitudinal Study on the Interplay of Personal and Social Identity
      in Adolescence.
AB  - The development of personal and social identity is crucial in adolescence. On the
      one hand, adolescents face the task of forming and consolidating their personal
      identity in multiple domains, with educational and interpersonal domains
      particularly salient. On the other hand, they enlarge their social horizon and
      increasingly define themselves as members of multiple peer groups, such as groups
      of classmates and friends met outside school. There is however a lack of
      integrative research on the interplay among and between personal and social
      identity processes. Hence the purpose of this study was threefold. First, we
      examined how personal identity processes in the educational and interpersonal
      domains are associated longitudinally. Second, we investigated to what extent
      social identifications with classmates and with the group of friends are
      associated over time. Third, with an original approach we examined the
      longitudinal interplay between personal and social identity processes, to connect
      theoretical contributions that have so far proceeded largely in parallel.
      Participants were 304 adolescents (61.84% female, M age = 17.49) involved in a
      three-wave longitudinal study. We found that (a) the ways in which adolescents
      develop their identity in the educational and interpersonal domains become more
      closely intertwined over time; (b) identifications with classmates and with the
      group of friends are interconnected; and (c) personal and social identity
      processes are associated both concurrently and longitudinally, with most cross
      lagged effects showing that social identifications influence personal identity
      formation and consolidation in the interpersonal identity domain. Theoretical
      implications are discussed.

PMID- 29185206
TI  - Reciprocal Associations between Educational Identity and Vocational Identity in
      Adolescence: A Three-wave Longitudinal Investigation.
AB  - Education and vocation are core identity domains in adolescence. School is a
      normative social context in this developmental time frame and the formation of an
      educational identity is embedded in the goals that youth pursue in school. One of
      the main goals of education is to prepare young people for their future careers.
      Hence, educational identity should support the formation of vocational identity
      during adolescence. Considering the limited evidence on the longitudinal links
      between these two domain-specific identities, we conducted a three-wave
      investigation, testing the moderating role of age group, gender, and type of
      school. Participants (N = 1030; 59.3% female) were adolescents (M age  = 16.72
      years, SD age  = 1.23, age range 14-19 years) who completed self-report measures
      of educational and vocational identity three times during an academic year. We
      underscored reciprocal associations between educational identity and vocational
      identity. The results indicate that strong educational commitments supported the
      formation of strong vocational commitments across time. Adolescents who were
      involved in the in-depth exploration of their educational choices also reported
      more vocational exploration during the school year. In turn, vocational identity
      processes also supported educational identity formation, especially the
      reconsideration of educational commitments. In terms of moderators, we
      underscored that vocational commitment making and vocational flexibility
      bolstered educational commitment only in early-to-middle adolescents. Educational
      in-depth exploration fostered the identification with vocational commitments only
      in girls. Educational reconsideration of commitment promoted vocational self
      doubt only in adolescents attending work-bound high-schools. Implications for
      research and practice are discussed.

PMID- 29185207
TI  - Prosocial Behavior in Adolescence: Gender Differences in Development and Links
      with Empathy.
AB  - Although adolescents' prosocial behavior is related to various positive outcomes,
      longitudinal research on its development and predictors is still sparse. This 6
      wave longitudinal study investigated the development of prosocial behavior across
      adolescence, and examined longitudinal associations with perspective taking and
      empathic concern. Participants were 497 adolescents (M age t1 = 13.03 years, 43%
      girls) who reported on their prosocial behaviors, empathic concern, and
      perspective taking. The results revealed marked gender differences in the
      development of prosocial behavior. For boys, levels of prosocial behavior were
      stable until age 14, followed by an increase until age 17, and a slight decrease
      thereafter. For girls, prosocial behavior increased until age 16 years and then
      slightly decreased. Regarding longitudinal associations, empathic concern was
      consistently related to subsequent prosocial behavior. However, perspective
      taking was only indirectly related to prosocial behavior, via its effect on
      empathic concern. Tests of the direction of effects showed support for the notion
      that earlier prosocial behavior predicts subsequent empathy-related traits, but
      only for girls. The findings support cognitive-developmental and moral
      socialization theories of prosocial development and the primary role of moral
      emotions in predicting prosocial behaviors. Our findings inform strategies to
      foster prosocial behaviors by emphasizing moral emotions rather than moral
      cognitions during adolescence.

PMID- 29185209
TI  - Value of the Oxford classification of IgA nephropathy in children with Henoch
      Schonlein purpura nephritis.
AB  - BACKGROUND: The widely used International Study of Kidney Disease in Children
      (ISKDC) classification for Henoch-Schonlein purpura nephritis (HSPN) does not
      completely correlate with the clinical presentation and long-term prognosis of
      this disease. Primary IgA nephropathy (IgAN) and HSPN share common features;
      thus, the Oxford classification of IgAN might be useful in predicting the long
      term outcomes of HSPN. However, its value has not been confirmed in children with
      HSPN. METHODS: We selected children with HSPN diagnosed between 2003 and 2015,
      and reclassified their renal biopsies according to the Oxford classification
      scoring system. The primary outcome was impaired renal function, and remission of
      proteinuria and clinical remission were secondary outcomes. RESULTS: We included
      104 patients (58 males, 46 females) with a median age of 10 (4-17) years.
      Mesangial hypercellularity (M1) was strongly associated with proteinuria, and
      tubular atrophy/interstitial fibrosis (T1&2) and C2 (with crescents in > 25% of
      glomeruli) were associated with reduced estimated glomerular filtration rate
      (eGFR) at the time of biopsy. Patients with M1, endocapillary proliferation (E1),
      segmental glomerulosclerosis (S1), and crescents (C1&2) were more likely to have
      been treated with high-dose methylprednisolone. At univariate time-dependent
      analyses, S1 was strongly associated with the primary outcome (p = 0.025),
      whereas T1&2 was significantly negatively associated with proteinuria remission
      (p = 0.035) and clinical remission (p = 0.038). CONCLUSIONS: Our findings suggest
      that the Oxford classification is valid for children with HSPN. S and T lesions,
      which are ignored in the ISKDC classification, can be used to assess renal
      outcomes of HSPN, and such assessments are not affected by currently available
      treatments. The value of M, E and C lesions in predicting response to therapy and
      renal outcome warrants further study.

PMID- 29185208
TI  - Neighborhood or School? Influences on Alcohol Consumption and Heavy Episodic
      Drinking Among Urban Adolescents.
AB  - Little is known about the relative influences of neighborhood and school on the
      alcohol socialization process. Survey data from the Young in Oslo Study (N =
      10,038, mean age 17.1 years, 52% girls) were used to investigate the details of
      such influences, using cross-classified multilevel models. School and
      neighborhood contexts were equally important for ordinary alcohol use; however,
      neighborhood influences were mainly explained by individual and family factors,
      whereas peer-based sociocultural processes played a key role in explaining school
      effects. Neither context had much impact on heavy episodic drinking. The study
      suggests that "privileged" youth may be at risk of high alcohol consumption.
      Parental influences and peer-based sociocultural aspects of the school milieu
      should be considered in prevention efforts.

PMID- 29185210
TI  - Acute kidney injury based on the KDIGO criteria among ST elevation myocardial
      infarction patients treated by primary percutaneous intervention.
AB  - BACKGROUND: Acute kidney injury (AKI) following acute ST elevation myocardial
      infarction (STEMI) is associated with adverse outcomes. The recently proposed
      KDIGO criteria suggested modifications to the consensus classification system for
      AKI, namely lowering the threshold of increase in absolute serum creatinine and
      extending the time frame for AKI detection to 7 days. We evaluated the incidence,
      risk factors, and long-term mortality associated with AKI as classified by the
      KDIGO definition in a large single center cohort of consecutive STEMI patients.
      METHODS: We retrospectively studied 2122 consecutive STEMI patients undergoing
      primary percutaneous coronary intervention (PCI). Recruited patients were
      admitted between January 2008 and May 2016 to the cardiac intensive care unit
      with the diagnosis of acute STEMI. We compared the utilization of the KDIGO and
      consensus criteria for the diagnosis of AKI and its relation to long term
      mortality. RESULTS: The KDIGO criteria allowed the identification of more
      patients as having AKI (10.6 vs. 5.6%, p < 0.001) compared to the consensus
      criteria. Even mild elevation of serum creatinine (>= 0.3 mg/dL) was associated
      with a marked increase in all-cause mortality (HR 4.7, 95% CI 3.1-6.43, p <
      0.001). Patients with AKI whose renal function resolved prior to hospital
      discharge still had significantly higher mortality compared to patients with no
      AKI (23 vs. 8%, HR 3.1, 95% CI 2.09-4.90, p < 0.001). CONCLUSION: KDIGO criteria
      is more sensitive than the consensus criteria in defining AKI in STEMI patients
      and identifying populations at risk for long term adverse outcomes.

PMID- 29185211
TI  - Plasma EBV microRNAs in paediatric renal transplant recipients.
AB  - BACKGROUND: Epstein-Barr virus (EBV) was the first human virus identified to
      express microRNA (miRNA). To date, 44 mature miRNAs are encoded for within the
      EBV genome. EBV miRNAs have not been profiled in paediatric renal transplant
      recipients. In this study, we investigated circulating EBV miRNA profiles as
      novel biomarkers in paediatric renal transplant patients. METHODS: Forty-two
      microRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined
      in renal transplant recipients who resolved EBV infection (REI) or maintained
      chronic high viral loads (CHL), and in non-transplant patients with acute
      infectious mononucleosis (IM). RESULTS: Plasma EBV-miR-BART2-5p was present in
      higher numbers of IM (7/8) and CHL (7/10) compared to REI (7/12) patients. A
      trend was observed between the numbers of plasma EBV miRNAs expressed and EBV
      viral load (p < 0.07). Several EBV-miRs including BART7-3p, 15, 9-3p, 11-3p, 1-3p
      and 3-3p were detected in IM and CHL patients only. The lytic EBV-miRs, BHRF1-2
      3p and 1-1, indicating active viral replication, were detected in IM patients
      only. One CHL patient developed post-transplant lymphoproliferative disease
      (PTLD) after several years and analysis of 10 samples over a 30-month period
      showed an average 24-fold higher change in plasma EBV-miR-BART2-5p compared to
      the CHL group and 110-fold higher change compared to the REI group. CONCLUSIONS:
      Our results suggest that EBV-miR-BART2-5p, which targets the stress-induced
      immune ligand MICB to escape recognition and elimination by NK cells, may have a
      role in sustaining high EBV viral loads in CHL paediatric kidney transplant
      recipients.

PMID- 29185212
TI  - A semiparametric additive rate model for a modulated renewal process.
AB  - Recurrent event data from a long single realization are widely encountered in
      point process applications. Modeling and analyzing such data are different from
      those for independent and identical short sequences, and the development of
      statistical methods requires careful consideration of the underlying dependence
      structure of the long single sequence. In this paper, we propose a semiparametric
      additive rate model for a modulated renewal process, and develop an estimating
      equation approach for the model parameters. The asymptotic properties of the
      resulting estimators are established by applying the limit theory for stationary
      mixing sequences. A block-based bootstrap procedure is presented for the variance
      estimation. Simulation studies are conducted to assess the finite-sample
      performance of the proposed estimators. An application to a data set from a
      cardiovascular mortality study is provided.

PMID- 29185213
TI  - Carotid artery ligation induced intimal thickening and proliferation is
      unaffected by ageing.
AB  - Following interventions to treat atherosclerosis, such as coronary artery bypass
      graft surgery, restenosis occurs in approximately 40% of patients. Identification
      of proteins regulating intimal thickening could represent targets to prevent
      restenosis. Our group previously demonstrated that in a murine model of vascular
      occlusion, Wnt4 protein expression and beta-catenin signalling was upregulated
      which promoted vascular smooth muscle cell (VSMC) proliferation and intimal
      thickening. In this study, the effect of age on VSMC proliferation, intimal
      hyperplasia and Wnt4 expression was investigated. In vitro proliferation of VSMCs
      isolated from young (2 month) or old (18-20 month) C57BL6/J mice was assessed by
      immunocytochemistry for EdU incorporation. As previously reported, 400 ng/mL
      recombinant Wnt4 protein increased proliferation of VSMCs from young mice.
      However, this response was absent in VSMCs from old mice. As our group previously
      reported reduced intimal hyperplasia in Wnt4+/- mice compared to wildtype
      controls, we hypothesised that impaired Wnt4 signalling with age may result in
      reduced neointimal formation. To investigate this, carotid artery ligation was
      performed in young and old mice and neointimal area was assessed 21 days later.
      Surprisingly, neointimal area and percentage lumen occlusion were not
      significantly affected by age. Furthermore, neointimal cell density and
      proliferation were also unchanged. These data suggest that although Wnt4-mediated
      proliferation was impaired with age in primary VSMCs, carotid artery ligation
      induced neointimal formation and proliferation were unchanged in old mice. These
      results imply that Wnt4-mediated proliferation is unaffected by age in vivo,
      suggesting that therapeutic Wnt4 inhibition could inhibit restenosis in patients
      of all ages.

PMID- 29185214
TI  - The significance of preexisting medical conditions, alcohol/drug use and suicidal
      behavior for drivers in fatal motor vehicle crashes: a retrospective autopsy
      study.
AB  - Driver fatalities in motor vehicle collisions (MVCs) encompass accidents,
      suicides, and natural deaths when driving. The objective of this study was to
      determine the significance of pathology and other autopsy findings for drivers in
      fatal MVCs. Forensic autopsy records of driver fatalities in southeast Norway
      between 2000 and 2014 were studied retrospectively. Data from individual police
      and collision investigation reports were also collected and analyzed. In 406
      driver fatalities, the male/female ratio was 340/66; 9% died from natural causes,
      9% were suicides, 65% were culpable accidental deaths, 14% were nonculpable
      deaths, and 3% were undetermined deaths. Head injuries and thoracic injuries were
      the most common causes of death. A seatbelt had been worn in 50% of the
      fatalities, and its prevalence did not differ between accidental deaths and
      suicides. Blood levels of alcohol and/or drugs that indicated impairment at the
      time of the collision were found in 40% (105/262) of all culpable accidental
      deaths but in 50% (64/127) of drivers aged up to 35 years. Pathology (most often
      cardiovascular disease) suggestive of sudden incapacitation before the collision
      was present in 24% (62/264) of drivers who were culpable in the accident and in
      70% (46/66) of culpable drivers older than 55 years. A substantial proportion of
      drivers are killed in accidental collisions that may have occurred as a result of
      either alcohol/drug impairment or preexisting disease. Suicides and natural
      deaths both constitute significant proportions of MVC fatalities and may be
      misclassified unless a full inquest including an autopsy is performed.

PMID- 29185215
TI  - Nickle(II) ions exacerbate bleomycin-induced pulmonary inflammation and fibrosis
      by activating the ROS/Akt signaling pathway.
AB  - Nickle (Ni) is a heavy metal found in particulate matter. We previously reported
      that Ni ions are strongly associated with high apoptosis rates and high
      expression of IL-1beta in human bronchial epithelial cells following exposure to
      PM2.5; however, the effects of Ni ions on pulmonary fibrosis have not been fully
      elucidated. In the current study, we evaluated whether Ni ions can exacerbate
      bleomycin (BLM)-induced pulmonary fibrosis in a mouse model and illustrated the
      potential mechanism. Ni ions inhibited cell proliferation and induced apoptosis
      in A549 and MRC-5 cells. BLM-induced lung injury and fibrosis in mice were
      significantly enhanced by nickel treatment, and these findings were also
      supported by inflammatory cell accumulation in bronchoalveolar lavage fluid and
      elevated levels of pro-inflammatory cytokines in lung tissues. Ni ions also
      increased extracellular matrix protein levels, including those of type I collagen
      and MMP9 in mouse lung tissues and cell lines. Moreover, Ni ions promoted the
      phosphorylation of AKT in this mouse model. The effect of increased collagen
      levels and MMP9 expression was inhibited by blocking the AKT phosphorylation.
      Together, these findings suggest AKT activation as a critical contributor to this
      Ni-exacerbated pulmonary fibrotic process.

PMID- 29185216
TI  - Heterogeneous activation of peroxymonosulfate by hierarchical CuBi2O4 to generate
      reactive oxygen species for refractory organic compounds degradation: morphology
      and surface chemistry derived reaction and its mechanism.
AB  - Activation of peroxymonosulfate (PMS) by a novel hierarchical CuBi2O4 generated
      reactive oxygen radical for degradation refractory organic compounds in aqueous
      solution, which would be controlled by the morphology and surface chemistry of
      solid catalyst. It's found that the activation ability of CuBi2O4 toward PMS was
      highly dependent on the morphology and surface hydroxyl group, as using rhodamine
      B (RhB) as the model compound. The spherical CuBi2O4, which possessed higher
      density of surface hydroxyl group, exhibited better catalytic activity in RhB
      degradation than scattered cluster CuBi2O4, and as-prepared CuBi2O4 could
      efficiently activated PMS to degrade RhB within a wide pH range as an absolute
      heterogeneous process. The emerging organic chemicals, including bisphenol A, 1H
      benzotriazole, and carbamazepine, could also be effectively removed in this novel
      CuBi2O4/PMS. Furthermore, activation mechanism of PMS by as-prepared CuBi2O4 was
      proposed, the existence of surface hydroxyl group bonded with Cu(II), and inward
      electron transfer cycling reaction between Cu(II)/Cu(I) facilitated the effective
      activation of PMS to generate SO4.- and .OH. In addition, the intermediates of
      RhB formed in this process were identified by silylation derivatation-GC-MS and
      LC-high-resolution MS/MS, and degradation pathway was proposed.

PMID- 29185217
TI  - Correction to: Heavy metal and nutrient uptake in plants colonizing post
      flotation copper tailings.
AB  - The correct presentation of Table 4 is shown in this paper.

PMID- 29185218
TI  - Correction to: Strict anaerobic side-stream reactor: effect of the sludge
      interchange ratio on sludge reduction in a biological nutrient removal process.
AB  - The correct Fig. 1 is shown in this paper.

PMID- 29185219
TI  - Study on the pollution status and control measures for the livestock and poultry
      breeding industry in northeastern China.
AB  - Livestock and poultry breeding industry is one of the main economic pillars of
      northeastern China. However, the amount of pollutants produced is much higher
      than that in other parts of China. Through a questionnaire survey, indoor
      experiment, and outdoor experiment, it was found that the resource utilization
      rate of livestock and poultry manure in the northeastern region is low, with the
      pollution of livestock and poultry breeding mainly including air and water
      pollution. The alarm level of cultivated land and manure is II. While the
      livestock and poultry breeding is relatively concentrated area, its level is
      higher than grade II. Based on the pollution status of small farms, biogas can be
      produced through fermentation, along with the preparation of organic fertilizer,
      to completely utilize the manure and straw, while obtaining higher economic
      value, and effectively controlling the pollution from livestock and poultry
      breeding.

PMID- 29185220
TI  - A review on pesticide removal through different processes.
AB  - The main organic pollutants worldwide are pesticides, persistent chemicals that
      are of concern owing to their prevalence in various ecosystems. In nature,
      pesticide remainders are subjected to the chemical, physical, and biochemical
      degradation process, but because of its elevated stability and some cases water
      solubility, the pesticide residues persist in the ecosystem. The removal of
      pesticides has been performed through several techniques classified under
      biological, chemical, physical, and physicochemical process of remediation from
      different types of matrices, such as water and soil. This review provides a
      description of older and newer techniques and materials developed to remove
      specific pesticides according to previous classification, which range from
      bioremediation with microorganisms, clay, activated carbon, and polymer materials
      to chemical treatment based on oxidation processes. Some types of pesticides that
      have been removed successfully to large and small scale include,
      organophosphorus, carbamates, organochlorines, chlorophenols, and synthetic
      pyrethroids, among others. The most important characteristics, advantages, and
      disadvantages of techniques and materials for removing pesticides are described
      in this work.

PMID- 29185221
TI  - Toxicity evaluation of textile effluents and role of native soil bacterium in
      biodegradation of a textile dye.
AB  - Water pollution caused by the discharge of hazardous textile effluents is a
      serious environmental problem worldwide. In order to assess the pollution level
      of the textile effluents, various physico-chemical parameters were analyzed in
      the textile wastewater and agricultural soil irrigated with the wastewater
      (contaminated soil) using atomic absorption spectrophotometer and gas
      chromatography-mass spectrometry (GC-MS) analysis that demonstrated the presence
      of several toxic heavy metals (Ni, Cu, Cr, Pb, Cd, and Zn) and a large number of
      organic compounds. Further, in order to get a comprehensive idea about the
      toxicity exerted by the textile effluent, mung bean seed germination test was
      performed that indicated the reduction in percent seed germination and radicle
      plumule growth. The culturable microbial populations were also enumerated and
      found to be significantly lower in the wastewater and contaminated soil than the
      ground water irrigated soil, thus indicating the biotic homogenization of
      indigenous microflora. Therefore, the study was aimed to develop a cost effective
      and ecofriendly method of textile waste treatment using native soil bacterium,
      identified as Arthrobacter soli BS5 by 16S rDNA sequencing that showed remarkable
      ability to degrade a textile dye reactive black 5 with maximum degradation of 98%
      at 37  degrees C and pH in the range of 5-9 after 120 h of incubation.

PMID- 29185222
TI  - Health risk evaluation of heavy metals in green land soils from urban parks in
      Urumqi, northwest China.
AB  - Here, we sampled, tested, and analyzed heavy metals in soil obtained from green
      land in urban parks of Urumqi. Analysis included soil nutrient contents, particle
      size distribution, and health risks of heavy metal contaminants. Results showed
      that (1) organic matter and rapidly available phosphorus contents of all samples
      ranged from 6.07-58.34 and 6.52-116.15 mg/kg, with average values of 31.26 and
      36.24 mg/kg, respectively; (2) silt (particle size 20-200 MUm) comprised most of
      the particle distribution, accounting for 46.56-87.38% of the total, and the
      remaining particles were clay particles (0-20 MUm) and sand (200-2000 MUm); (3)
      calculations of HQing, HQinh, and HQderm for eight heavy metals in three exposure
      patterns revealed values less than 1 for children and adults, indicating a level
      of carcinogenic risk for these heavy metals; and (4) calculating the carcinogenic
      risks of nickel, chromium, and cadmium through breathing pathway indicating no
      potential carcinogenic risk for any of the three. This research showed high soil
      nutrient content, providing fertile ground for plant growth in the green land of
      these urban parks. However, measures such as using sprinklers and increased green
      vegetation areas have been proposed to improve soil texture. This research can
      serve as a reference point for soil environmental protection efforts as well as
      future plant growth in urban Urumqi parks.

PMID- 29185223
TI  - Role of nature reserves in giant panda protection.
AB  - Giant panda (Ailuropoda melanoleuca) is a flagship species in nature conservation
      of the world; to protect this species, 67 nature reserves have been established
      in China. To evaluate the protection effect of giant panda nature reserves, we
      analyzed the variation of giant panda number and habitat area of 23 giant panda
      nature reserves of Sichuan province based on the national survey data released by
      State Forestry Administration and Sichuan Forestry Department. Results showed
      that from the third national survey to the fourth, giant panda number and habitat
      area of 23 giant panda nature reserves of Sichuan province failed to realize the
      significant increase. Furthermore, we found that the total population growth rate
      of 23 nature reserves in the last 12 years was lower than those of the province
      total of Sichuan and the national total of China, and the total habitat area of
      the 23 nature reserves was decreasing in the last 12 years, but the province
      total and national total were all increasing. We propose that giant panda
      protection should pay more attention to how to improve the protective effects of
      nature reserves.

PMID- 29185224
TI  - The impact of hydro-biofuel-wind energy consumption on environmental cost of
      doing business in a panel of BRICS countries: evidence from three-stage least
      squares estimator.
AB  - The renewable energy sources are considered the vital factor to promote global
      green business. The environmental cost of doing business is the pre-requisite to
      analyze sustainable policies that facilitate the eco-minded entrepreneurs to
      produce healthier goods. This study examines the impact of renewable energy
      sources (i.e., hydro energy, biofuel energy, and wind energy) on the
      environmental cost of doing business in a panel of BRICS (Brazil, Russian
      Federation, India, China, and South Africa) countries, for the period of 1995
      2015. The study employed principal component analysis to construct an "integrated
      environmental index" by using three alternative and plausible factors including
      carbon dioxide emissions, fossil fuel energy consumption, and chemicals used in
      the manufacturing process. The environmental index is used as an interactive term
      with the three cost of doing business indicators including business disclosure
      index, the cost of business start-up procedures, and logistics performance index
      to form environmental cost of doing business (ECDB) indicators. The results of
      three-stage least squares (3SLS) estimator show that foreign direct investment
      (FDI) inflows supported the green business while trade openness deteriorates the
      environment, which partially validates the "pollution haven hypotheses (PHH)" in
      a panel of countries. There is no evidence for environmental Kuznets curve (EKC)
      hypothesis; however, there is a monotonic decreasing relationship between per
      capita income and ECDB indicators. The hydro energy supports the sustainable
      business environment, while biofuel consumption deteriorates the environmental
      impact on the cost of business start-up procedures. Finally, wind energy
      subsequently affected the ECDB indicators in a panel of BRICS countries. The
      overall results conclude that growth factors and energy sources both have a
      considerable impact on the cost of doing business; therefore, there is a
      momentous need to formulate sustainable policy vista to magnetize green business
      across countries.

PMID- 29185225
TI  - Imperative roles of halotolerant plant growth-promoting rhizobacteria and kinetin
      in improving salt tolerance and growth of black gram (Phaseolus mungo).
AB  - The salinity stress causes a major threat for plant growth, yield, and biomass
      production. The present study was designed to assess the effect of exogenously
      applied kinetin and halotolerant plant growth-promoting rhizobacteria (H-PGPR) on
      alleviation of salt stress in black gram (Phaseolus mungo). A total of 15
      rhizobacterial isolates obtained from a salt-affected area were analyzed for
      their capability to improve growth of P. mungo plants growing in greenhouse
      conditions. Out of the tested rhizobacteria, the two bacterial isolates which
      exhibited maximum growth potential were screened and their growth-promoting
      attributes were evaluated. The role of screened H-PGPR and/or kinetin (8 and 10
      MUM) was evaluated in P. mungo plants irrigated with three levels of brackish
      water (S1 = 3, S2 = 5, and S3 = 7 dSm-1) under field condition. Salt stress
      reduced transpiration rate, stomatal conductance, salt tolerance index, growth,
      leaf area, photosynthetic pigments, leaf relative water content (LRWC), biomass
      production, and seed yield in subjected plants. Conversely, the salinized plants
      treated with kinetin and/or H-PGPR exhibited improved levels of chlorophyll
      contents, LRWC, root growth, shoot growth, biomass production, and seed yield.
      The H-PGPR and/or kinetin supplementation also reduced electrolyte leakage in
      salt-stressed plants. Overall, the present findings will be of great value to
      recognize the mechanism of salt stress alleviation in P. mungo plants under the
      influence of H-PGPR and/or kinetin.

PMID- 29185226
TI  - Assessment of three plant-based biodiesels using a Daphnia magna bioassay.
AB  - Biodiesel is an alternative fuel that is gradually replacing petroleum-based
      diesel use. Although biodiesel is considered friendlier to the environment, the
      potential toxic effects of biodiesel to aquatic organisms are still uncertain due
      to the wide range of feedstocks used to generate the fuel. The aquatic cladoceran
      Daphnia magna (D. magna) has been commonly used as a lethal and/or sub-lethal
      toxicological model organism in ecological risk assessments for contaminated
      water environments. In this work, we evaluated whether significant differences
      exist in the sensitivity of freshwater aquatic life to different biodiesels. The
      acute toxicity of three plant-based biodiesels was investigated using D. magna
      over a 96-h period. In addition, diesel fuel was tested as a reference. Increased
      immobility was observed as time progressed following exposure. Testing revealed
      of the four fuel products, diesel proved most toxic to D. magna, with half
      maximal effective concentration (EC50) values of 4.7 MUg/mL (24 h) and 3.4 MUg/mL
      (72 h). Among the biodiesels, safflower methyl biodiesel was most toxic, with
      EC50 values of 1026 MUg/mL (24 h) and 71 MUg/mL (48 h). Our data indicate that
      although not all biodiesels were toxic, the short-term exposure of D. magna to
      sub-lethal concentrations of biodiesels affects their mobility and thus decreases
      their reproductive potential. Overall, this research provides insights into the
      sub-lethal effects of biodiesels on an aquatic organism.

PMID- 29185227
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the
      management of pseudomyxoma peritonei: A single-center experience.
AB  - BACKGROUND AND AIMS: Pseudomyxoma peritonei (PMP) results from perforated
      appendiceal tumors. It is usually diagnosed preoperatively by imaging.
      Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy
      (HIPEC), although aggressive long procedure with high complications rate, was
      considered the optimal treatment. This study is aiming to study the role of CRS
      and HIPEC in the management of PMP and assess the outcome. METHODS: This is a
      retrospective study which was conducted at King Faisal Hospital and Research
      Center, a tertiary care hospital during the period from November 2008 to June
      2016. Approval of the Research Advisory Council was obtained. Forty-one
      procedures of CRS and HIPEC were performed in 38 patients. Using the open abdomen
      technique, CRS was performed using standard peritonectomy procedures and visceral
      resections directed toward the complete elimination of tumors from abdominopelvic
      cavity. HIPEC was performed using mitomycin C in a dose of 30 mg/m2 and allowed
      to circulate in abdominopelvic cavity for 90 min at 41.0 to 42.2  degrees C.
      RESULTS: Forty-one procedures were performed in 38 patients. Three procedures
      were done as repeat CRS and HIPEC. No perioperative mortality. Cystoscopy and
      bilateral ureteric stents in 35 procedures (85.5%). Hospital stay (range 9-85
      days) average is 21 days. Follow up period is 1-84 months, and median follow up
      is 54 months. Five-year survival rate is 92%. Median 5-year disease-free survival
      rate is 60%. Two patients died during the follow up period by septic shock and
      one patient died from disease progression. CONCLUSION: CRS and HIPEC is well
      tolerated and feasible management for PMP.

PMID- 29185228
TI  - Deceased donor liver transplant: Experience from a public sector hospital in
      India.
AB  - BACKGROUND: Deceased donor liver transplant (DDLT) is an uncommon procedure in
      India. We present our experience of DDLT from a public sector teaching hospital.
      METHODS: A retrospective analysis of all DDLT was performed from April 2012 till
      September 2016. Demographics, intraoperative, donor factors, morbidity, and
      outcome were analyzed. RESULTS: During the study period, 305 liver transplants
      were performed, of which 36 were DDLT (adult 32, pediatric 4; 35 grafts; 1
      split). The median age was 42.5 (1-62) years; 78% were men. The median donor age
      was 28 (1-77) years; 72.2% were men. About 45% of organs were procured from
      outside of Delhi and 67% of all grafts used were marginal. Three of 38 liver
      grafts (7.8%) were rejected due to gross steatosis. Commonest indication was
      cryptogenic cirrhosis (19.4%). The median model for end-stage liver disease
      sodium and pediatric end-stage liver disease scores were 23.5 (9-40) and 14.5 (9
      22), respectively. Median warm and cold ischemia times were 40 (23-56) and 396
      (111-750) min, respectively. Major morbidity of grade III and above occurred in
      63.8%. In hospital (90 days), mortality was 16.7% and there were two late deaths
      because of chronic rejection and biliary sepsis. The overall survival was 77.8%
      at median follow up of 8.6 (1-54) months. CONCLUSIONS: DDLT can be performed with
      increasing frequency and safety in a public sector hospital. The perioperative
      and long-term outcomes are acceptable despite the fact that most organs were
      extended criteria grafts.

PMID- 29185229
TI  - Overexpression of insulin receptor substrate-4 is correlated with clinical
      staging in colorectal cancer patients.
AB  - Insulin receptor substrate-4 (IRS-4), a poorly studied member of the IRS family,
      may play an important role in colorectal cancer (CRC) tumourigenesis. The aim of
      this pilot study was to elucidate the potential role of IRS-4 in colorectal
      carcinogenesis by evaluating IRS-4 expression in different types of colorectal
      tumours (n = 20) and comparing its expression to normal mucosa (n = 20). Tissue
      samples were collected from 18 patients with CRC and 2 with precancerous lesions
      (tubulovillous adenomas), all of whom were undergoing potentially curative
      surgery. IRS-4 expression was evaluated using immunohistochemical staining and
      compared to clinicopathological features. In normal colonic crypts, the
      subcellular localization of IRS-4 varied from the crypt base compartment to the
      surface epithelium. Nuclear IRS-4 staining decreased while non-nuclear IRS-4
      increased as cells approached the top of the crypt. In the patients studied,
      colorectal tumours showed a significant (p < 0.001) increase of IRS-4 expression
      compared with adjacent normal tissue. Furthermore, nuclear IRS-4 intensity of CRC
      patients was significantly (p < 0.0001) higher in colonic tumoural tissue than in
      paired normal specimens. Tumour expression of IRS-4 in CRC patients was
      positively associated with T (p < 0.0001) and N (p < 0.05), of TNM (tumour and
      nodes and metastasis) staging system. Taken together, these results suggest that
      increase of IRS-4 expression may be involved to some extent in colorectal cancer.

PMID- 29185230
TI  - Molecular Epidemiology of Rotavirus Strains in Under Five Children.
AB  - OBJECTIVES: To determine the prevalence and genotype distribution of rotaviruses
      in children presenting to authors' hospital in Middle Black Sea region of Turkey.
      The results may supply important information about vaccine studies in Turkey.
      METHODS: Rotavirus antigen was detected by latex agglutination test and rotavirus
      RNA was detected by RT-PCR test. On the other hand, rotavirus positive samples
      were genotyped by semi-nested multiplex polymerase chain reaction. RESULTS: The
      highest rate of rotavirus positivity (46.9%) was observed among children in the
      13 to 24 mo age group. All the positive-strains were in G1-4, G8-9, P [4], P [8],
      and P [9] genotypes. The most common G and P combination in present study was
      G9P[8] (n = 24, 28.9%). CONCLUSIONS: The present results indicated that the most
      prevalent genotypes were G1, G9, P8, G9P[8] and G1P[8] in authors' region.
      Rotavirus vaccines used in this region must include mainly these genotypes.

PMID- 29185231
TI  - Translating Asthma: Dissecting the Role of Metabolomics, Genomics and
      Personalized Medicine.
AB  - The management of asthma has largely stagnated over the last 25 years, but we are
      at the dawning of a new age wherein -omics technology can help us manage the
      disease objectively and rationally. Even in this new scientific age, getting the
      basics of asthma management right remains essential. The new technologies which
      can be applied to multiple biological samples include genomics (study of the
      genome), transcriptomics (gene transcription), lipidomics, proteomics and
      metabolomics (lipids, proteins and metabolites, respectively) and breathomics,
      using exhaled breath as a source of biomarkers, which is of particular interest
      in view of its non-invasive nature in pediatrics. Important applications will
      include the diagnosis of airways disease, including its components; the pathways
      driving airway pathology; monitoring the response to treatment; and measuring
      future risk (asthma attacks, poor lung growth trajectory). With the advent of a
      wide range of novel biologicals to treat asthma, -omics technology to personalize
      therapy will be especially important. The U-BIOPRED (Europe) and SARP (USA)
      groups have been most active in this field, especially using bronchoscopically
      obtained samples to perform cluster analyses to define new asthma endotypes.
      However, stability over time and consistency between investigators is imperfect.
      This is perhaps unsurprising; results of biomarker studies in asthma will be a
      composite of the underlying disease, the (variable) effects of adverse drivers
      such as allergen exposure and pollution, the effects of treatment, and the
      effects of adherence or otherwise to treatment. Ultimately, the aim should be an
      exhaled breath based tool with a rapid result that can be used as a routine in
      the clinic. However, at the moment, there are as yet no clinical applications in
      children of -omics technology.

PMID- 29185232
TI  - Impaired taste sensation in type 2 diabetic patients without chronic
      complications: a case-control study.
AB  - PURPOSE: Few and contradictory data suggest changes in taste perception in type 2
      diabetes (T2DM), potentially altering food choices. We, therefore, analyzed taste
      recognition thresholds in T2DM patients with good metabolic control and free of
      conditions potentially impacting on taste, compared with age-, body mass index-,
      and sex-matched normoglycemic controls. METHODS: An ascending-concentration
      method was used, employing sucrose (sweet), sodium chloride (salty), citric acid
      (sour), and quinine hydrochloride (bitter), diluted in increasing concentration
      solutions. The recognition threshold was the lowest concentration of correct
      taste identification. RESULTS: The recognition thresholds for the four tastes
      were higher in T2DM patients. In a multiple regression model, T2DM [beta = 0.95;
      95% CI 0.32-1.58; p = 0.004 (salty); beta = 0.61; 0.19-1.03; p = 0.006 (sweet);
      beta = 0.78; 0.15-1.40; p = 0.016 (sour); beta = 0.74; 0.22-1.25; p = 0.006
      (bitter)] and waist circumference [beta = 0.05; 0.01-0.08; p = 0.012 (salty);
      beta = 0.03; 0.01-0.05; p = 0.020 (sweet); beta = 0.04; 0.01-0.08; p = 0.020
      (sour); beta = 0.04; 0.01-0.07; p = 0.007 (bitter)] were associated with the
      recognition thresholds. Age was associated with salty (beta = 0.06; 0.01-0.12; p
      = 0.027) and BMI with sweet thresholds (beta = 0.06; 0.01-0.11; p = 0.019).
      CONCLUSIONS: Taste recognition thresholds were higher in uncomplicated T2DM, and
      central obesity was significantly associated with this impairment. Hypogeusia may
      be an early sign of diabetic neuropathy and be implicated in the poor compliance
      of these patients to dietary recommendations.

PMID- 29185233
TI  - Estimating Prevalence and Healthcare Utilization for Treatment-Resistant
      Depression in Japan: A Retrospective Claims Database Study.
AB  - BACKGROUND: Major depressive disorders (MDDs) including treatment-resistant
      depression (TRD) are common disabling conditions, but data on their epidemiology
      in Japan are limited. This study investigated the incidence, epidemiology, and
      direct medical costs of TRD and pharmaceutically-treated depression (PTD) in
      Japan to increase our health economic understanding of this phenotype of MDD.
      METHODS: A retrospective cohort study from a private health insurance claims
      database estimated the 1-year incidence of PTD and TRD and described the health
      services used and direct medical costs associated with these conditions. RESULTS:
      In the year from 1 April 2012 through 31 March 2013, we identified 1143 incident
      PTD cases among 98,552 eligible subjects, i.e. 11.59 cases/1000 patient-years. Of
      the PTD patients, 51.4% were women. Within the 1-year observation interval 137
      patients failed more than two antidepressive treatment approaches and thus
      developed TRD. Though co-morbid conditions and age were similar among PTD and TRD
      patients, medical costs per patient (patient-year) during their treatment
      intervals were 1.01 million JPY (0. 540 million JPY) in the TRD population and
      0.643 JPY million JPY (0.645 million JPY) in the PTD population who did not
      convert into TRD. CONCLUSIONS: This study describes the PTD and TRD patient
      populations in a large claims database in Japan and highlights an unmet medical
      need for the treatment of TRD to provide better preventative measures and
      interventions for the treatment of depression.

PMID- 29185234
TI  - Newly Isolated Lactobacilli strains from Algerian Human Vaginal Microbiota:
      Lactobacillus fermentum Strains Relevant Probiotic's Candidates.
AB  - Lactobacilli strains are considered as a preventive means for treatment of
      vaginal infections or post-antibiotic treatment to repopulate the vaginal mucosa.
      This study aimed at establishing the vaginal lactobacillus profile of Algerian
      women with different vaginal diseases. Afterwards, lactobacilli isolated from
      swabs were in vitro characterized for their probiotic hallmarks. This prospective
      study allowed isolation of 44 Lactobacillus strains and 160 potentially
      pathogens, among which are Escherichia coli (50 isolates), Staphylococcus sp. (38
      isolates), Enterococcus sp. (16 isolates), and Candida sp. (56 isolates). All
      Lactobacilli strains were characterized for their antagonism, adhesion to
      polystyrene, and resistance to acidity and bile. Consequently, six Lactobacillus
      strains (Lb. fermentum 5LB4, 5LB10, 5LB12, Lb. plantarum 5LB2, 5LB11, and
      Lactobacillus sp. 4LB9) were moderately or weakly adherent, and 35 potentially
      pathogens exhibited weak to strong adhesion to polystyrene. Antagonism was
      recorded for 36 Lactobacillus strains towards E. coli 6E2, S. aureus 7S3,
      Enterococcus sp. 5EN8, and Candida albicans C1 used as indicator organisms.
      Finally, Lb. fermentum 9LB6, 4LB16, and 10LB1 and Lb. plantarum 9LB4 were
      remarkable for their inhibitory activity, absence of hemolytic potential, and for
      their resistance to acidity (pH 1.5) and bile (0.5%) harsh conditions.

PMID- 29185235
TI  - Erratum to: Introduction to Cancer Stem Cells: Past, Present, and Future.

PMID- 29185236
TI  - An Automated System Combining Safety Signal Detection and Prioritization from
      Healthcare Databases: A Pilot Study.
AB  - INTRODUCTION: Signal detection from healthcare databases is possible, but is not
      yet used for routine surveillance of drug safety. One challenge is to develop
      methods for selecting signals that should be assessed with priority. AIM: The aim
      of this study was to develop an automated system combining safety signal
      detection and prioritization from healthcare databases and applicable to drugs
      used in chronic diseases. METHODS: Patients present in the French EGB healthcare
      database for at least 1 year between 2005 and 2015 were considered. Noninsulin
      glucose-lowering drugs (NIGLDs) were selected as a case study, and
      hospitalization data were used to select important medical events (IME). Signal
      detection was performed quarterly from 2008 to 2015 using sequence symmetry
      analysis. NIGLD/IME associations were screened if one or more exposed case was
      identified in the quarter, and three or more exposed cases were identified in the
      population at the date of screening. Detected signals were prioritized using the
      Longitudinal-SNIP (L-SNIP) algorithm based on strength (S), novelty (N), and
      potential impact of signal (I), and pattern of drug use (P). Signals scored in
      the top 10% were identified as of high priority. A reference set was built based
      on NIGLD summaries of product characteristics (SPCs) to compute the performance
      of the developed system. RESULTS: A total of 815 associations were screened and
      241 (29.6%) were detected as signals; among these, 58 (24.1%) were prioritized.
      The performance for signal detection was sensitivity = 47%; specificity = 80%;
      positive predictive value (PPV) 33%; negative predictive value = 82%. The use of
      the L-SNIP algorithm increased the early identification of positive controls,
      restricted to those mentioned in the SPCs after 2008: PPV = 100% versus PPV = 14%
      with its non-use. The system revealed a strong new signal with
      dipeptidylpeptidase-4 inhibitors and venous thromboembolism. CONCLUSION: The
      developed system seems promising for the routine use of healthcare data for
      safety surveillance of drugs used in chronic diseases.

PMID- 29185237
TI  - Using Human 'Experiments of Nature' to Predict Drug Safety Issues: An Example
      with PCSK9 Inhibitors.
AB  - INTRODUCTION: When a new drug enters the market, its full array of side effects
      remains to be defined. Current surveillance approaches targeting these effects
      remain largely reactive. There is a need for development of methods to predict
      specific safety events that should be sought for a given new drug during
      development and postmarketing activities. OBJECTIVE: We present here a safety
      signal identification approach applied to a new set of drug entities, inhibitors
      of the serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9).
      METHODS: Using phenome-wide association study (PheWAS) methods, we analyzed
      available genotype and clinical data from 29,722 patients, leveraging the known
      effects of changes in PCSK9 to identify novel phenotypes in which this protein
      and its inhibitors may have impact. RESULTS: PheWAS revealed a significantly
      reduced risk of hypercholesterolemia (odds ratio [OR] 0.68, p = 7.6 * 10-4) in
      association with a known loss-of-function variant in PCSK9, R46L. Similarly,
      laboratory data indicated significantly reduced beta mean low-density lipoprotein
      cholesterol (- 14.47 mg/dL, p = 2.58 * 10-23) in individuals carrying the R46L
      variant. The R46L variant was also associated with an increased risk of spina
      bifida (OR 5.90, p = 2.7 * 10-4), suggesting that further investigation of
      potential connections between inhibition of PCSK9 and neural tube defects may be
      warranted. CONCLUSION: This novel methodology provides an opportunity to put in
      place new mechanisms to assess the safety and long-term tolerability of PCSK9
      inhibitors specifically, and other new agents in general, as they move into human
      testing and expanded clinical use.

PMID- 29185238
TI  - Agreement Among Different Scales for Causality Assessment in Drug-Induced Liver
      Injury.
AB  - BACKGROUND AND OBJECTIVE: The causality assessment of drug-induced liver injury
      (DILI) remains a challenge and eagerly awaits the development of reliable
      hepatotoxicity biomarkers. None of the different available algorithms used for
      the causality assessment of DILI has been universally accepted as the gold
      standard. This study was conducted to examine the agreement among different
      causality assessment scales in reporting DILI. METHODS: The World Health
      Organization-Uppsala Monitoring Center (WHO-UMC), Naranjo, Roussel Uclaf
      Causality Assessment Method (RUCAM), Maria & Victorino (M & V) and Digestive
      Disease Week-Japan (DDW-J) assessment scales were used to compare the causalities
      in all the reported cases of DILI in our adverse drug reaction (ADR) monitoring
      centre from January 2014 to June 2017. The probability of the causality
      assessment was classified as 'definite', 'probable', 'possible' and 'unlikely'.
      The agreement obtained among the causality assessments was analysed using the
      weighted kappa (kappa w) test. RESULTS: A total of 33 cases of DILI were included
      in our analyses. Anti-tubercular therapy (ATT) and methotrexate were the drugs
      that most commonly caused DILI. The overall agreement among the different scales
      was poor. The best agreement was found between RUCAM and DDW-J scales (kappa w:
      0.685). CONCLUSION: There were discrepancies among the different causality scales
      in assessing DILI. This might be due to the different definitions of causality
      criteria and subjective variability during assessment. A personalised assessment
      scale incorporating the latest information on specific risk factors and evidence
      based criteria for DILI is warranted.

PMID- 29185239
TI  - Assessing the plight of young unaccompanied refugees.

PMID- 29185240
TI  - Insufficient recruitment and premature discontinuation of clinical trials in
      Switzerland: qualitative study with trialists and other stakeholders.
AB  - AIMS OF THE STUDY: Premature discontinuation occurs in about 25% of randomised
      clinical trials in Switzerland; it mainly affects investigator-initiated trials
      and is mostly due to problems with recruitment of patients. The aim of this study
      was to qualitatively investigate reasons for trial discontinuation due to poor
      patient recruitment and suggestions to address those reasons in the Swiss
      context. METHODS: We conducted semi-structured interviews with trialists whose
      trials were discontinued because of recruitment problems, other experienced
      trialists, and stakeholders in clinical research in Switzerland. Interviews were
      audio-recorded, transcribed verbatim, and anonymised. We analysed the transcripts
      using deductive coding and built up themes that were continuously discussed
      within the research team. RESULTS: Of 65 invited Swiss trialists and
      stakeholders, 39 (60%) agreed to be interviewed and contributed to this analysis.
      We identified four main themes of reasons for poor recruitment: (1) Switzerland
      has a decentralised healthcare system with many small hospitals and few patients
      per hospital, many research regulations, no standardisation of medical records
      across hospitals, and a heterogeneous ethics assessment of study protocols. There
      is little collaboration of different stakeholders in clinical research and a lack
      of prioritisation of projects. (2) Limited human and financial resources,
      especially in the academic setting, compromise research questions and size of
      clinical trials. When funding is used up this typically triggers discontinuation
      of already delayed clinical trials. (3) Investigators face underdeveloped
      research networks and a limited collaborative attitude among clinical
      researchers. They typically embark on clinical studies with a great deal of
      optimism but insufficient preparation. (4) Swiss patients have universal health
      coverage and many treatment options. Negative media coverage of clinical research
      and a lack of accessible information for patients about ongoing clinical studies
      frequently make participation in clinical trials less attractive. More
      interactive structures and collaboration across stakeholders were mentioned as
      potential solutions to tackle the problems. CONCLUSIONS: Recruitment of
      participants into clinical trials in Switzerland is challenging because of
      various, often interlinked factors related to the Swiss health system, available
      funding, investigators, and patients. Common goals and concerted efforts by
      involved stakeholders appear necessary to achieve improvement.

PMID- 29185241
TI  - Quality indicators of colorectal cancer care in southern Switzerland: results
      from a population-based study.
AB  - AIM OF THE STUDY: Assessing the quality of cancer care (QoCC) has become
      increasingly relevant to providers, regulators and purchasers of healthcare
      worldwide. The aim of this study was to assess adherence to validated quality
      indicators (QIs) for colorectal cancer (CRC) in a population-based setting, and
      to compare results with the available literature. METHODS: All colorectal cancers
      diagnosed between 1 January 2011 and 31 December 2012 were identified from the
      files of the population-based Ticino Cancer Registry, southern Switzerland. We
      computed 12 core QIs, approved by use of the validated Delphi methodology and for
      which all the necessary medical documentation was available or only minor data
      collection was still needed to complete the analysis: three for diagnosis, two
      for pathology and seven for treatment (surgery, oncology and radiotherapy). Each
      QI was analysed as proportion (%) with 95% confidence interval, following the
      approach "available case analysis". RESULTS: A total of 474 colorectal cancers
      were identified: 86.9% patients were diagnosed after they reported symptoms,
      90.2% had preoperative colonoscopy, 8.7% underwent emergency surgery, 97.2% had a
      surgical resection with tumour-free margins, and for 86.6% at least 12 lymph
      nodes were examined. The overall 30-day postoperative mortality was 3.6% and
      66.7% of locally advanced rectal cancers benefited of neoadjuvant radiotherapy +/
      chemotherapy. CONCLUSIONS: Our study showed the feasibility of assessing QoCC
      using Cancer Registry population-based data. Results according to the clinical
      domain of pathology, surgery, oncology and radio-oncology in southern Switzerland
      are generally positive and encouraging, sometimes more favourable in comparison
      with other international studies, except the very low proportion of patients with
      a diagnosis based on opportunistic screening (8.6%). Considering the lack in the
      literature of population-based studies, further national and international
      reports are urgently needed for comparative analysis as well as standardisation
      of QI definition is absolutely necessary for inter-regional comparative goals.

PMID- 29185242
TI  - Costs and benefits of diagnostic testing: four ways to improve patient care by
      purposive use of in vitro diagnostics.
AB  - Scientific advances and innovative targeted drugs, especially biologics, have
      revolutionised the treatment of many diseases. In oncology in particular,
      previously acute or lethal conditions have come to be considered chronic as new
      treatments have led to longer life expectancies and a lower rate of years lived
      with disability. These advances, however, come with rising costs in a resource
      constrained environment. To achieve cost containment, reimbursement for in-vitro
      diagnostics (IVDs) is increasingly coming under pressure because they are
      perceived as a cost factor rather than as a tool to reduce expenditure in the
      long term. In this conceptual paper, we propose four possible interventions from
      an industry perspective that may contribute to increase effectiveness of IVD use
      to counteract increasing healthcare expenditures. These are: (1) fostering
      prevention, screening, early diagnosis and therapy; promoting (2) comprehensive
      and (3) stratified disease management; and (4) using targeted treatment alongside
      companion diagnostics. We conclude that the implementation of policies that
      promote a fee-for-outcome model rather than fee-for-service reimbursement can
      support sustainable healthcare.

PMID- 29185243
TI  - Risk of adverse outcome in patients referred by emergency medical services in
      Switzerland.
AB  - AIMS OF THE STUDY: Comparison of outcomes between different emergency medical
      services (EMS) is difficult and lacking in Switzerland. Therefore, knowledge
      about the inherent risks of EMS-referred patients is important. Targeted
      interventions may benefit these patients by optimising resource allocation. We
      therefore aimed to study outcomes in EMS-referred patients presenting to a Swiss
      emergency department (ED). METHODS: Prospective observational study in all
      patients presenting to the ED of Basel University Hospital. Mode of referral was
      recorded (EMS or other). Univariate and multivariate linear, Poisson and logistic
      regression models were used. Crude and age/gender adjusted associations between
      mode of referral and outcomes were calculated. Outcomes were shown for admission,
      length of stay (LOS), in-hospital, and 1-year mortality. RESULTS: Of 5634
      patients presenting in the inclusion period, 4703 were screened, 4544 were
      included and 4287 were followed up for 365 days. Associations between EMS
      referral and several adverse outcomes were found and expressed as odds ratios
      (ORs) and geometric mean ratios (GMRs): hospital admission (OR 3.8, 95% CI 3.2
      4.5; p <0.001), intensive care unit (ICU) admission (OR 4.2, 95% CI 3.2-5.5, p
      <0.001), ED-LOS (GMR 1.2, 95% CI 1.1-1.2; p <0.001), in-hospital mortality (OR
      6.4, 95% CI 2.9-15.6; p <0.001) and 1-year mortality (OR 2.3, 95% CI 1.7-3.0; p
      <0.001). CONCLUSION: Patients referred by EMS have higher odds of admission to
      hospital and ICU, a longer ED LOS, and higher short- and long-term mortalities
      than the general ED population.

PMID- 29185244
TI  - Monobodies as possible next-generation protein therapeutics - a perspective.
AB  - Over the past two decades, hundreds of new somatic mutations have been identified
      in tumours, and a few dozen novel cancer therapeutics that selectively target
      these mutated oncoproteins have entered clinical practice. This development has
      resulted in clinical breakthroughs for a few tumour types, but more commonly
      patients' overall survival has not improved because of the development of drug
      resistance. Furthermore, only a very limited number of oncoproteins, largely
      protein kinases, are successfully targeted, whereas most non-kinase oncoproteins
      inside cancer cells remain untargeted. Engineered small protein inhibitors offer
      great promise in targeting a larger variety of oncoproteins with better efficacy
      and higher selectivity. In this article, I focus on a promising class of
      synthetic binding proteins, termed monobodies, that we have shown to inhibit
      previously untargetable protein-protein interactions in different oncoproteins. I
      will discuss the great promise alongside the technical challenges inherent in
      converting monobodies from potent pre-clinical target validation tools to next
      generation protein-based therapeutics.

PMID- 29185245
TI  - HPV-negative CIN3 and cervical cancer in Switzerland: any evidence of impact on
      screening policies?

PMID- 29185246
TI  - Is there a role for procalcitonin in differentiating uncomplicated and
      complicated diverticulitis in order to reduce antibiotic therapy? A prospective
      diagnostic cohort study.
AB  - AIMS OF THE STUDY: While studies show that antibiotic treatment for uncomplicated
      diverticulitis seems to have no benefit, most experts advocate antimicrobial
      therapy for complicated diverticulitis. However, even for uncomplicated
      diverticulitis, most clinicians are very reluctant to withhold antibiotics.
      Biomarkers could help to guide antibiotic therapy as this approach has been shown
      to be effective for acute respiratory infections. In this diagnostic cohort study
      we evaluated whether procalcitonin could be a biomarker to distinguish
      complicated from uncomplicated cases of diverticulitis. METHODS: Complicated
      diverticulitis was defined as having abscess formation or perforation diagnosed
      by abdominal computed tomography (CT) scan. In all patients with suspected
      diverticulitis, procalcitonin values were measured at admission and on day 2.
      These values were blinded for clinicians, and treatment was carried out according
      to the physician's judgement. Two groups (complicated vs uncomplicated
      diverticulitis) were defined. Patients who had received antibiotic treatment
      before admission were excluded. Difference in procalcitonin values was calculated
      for both groups using the Mann-Whitney test. Receiver operating characteristics
      (ROC) were calculated to determine cut-off values for procalcitonin according to
      the gold standard (abdominal CT scans). RESULTS: 115 patients were included for
      analysis. 35 patients (30%) suffered from complicated diverticulitis. The median
      procalcitonin value for uncomplicated diverticulitis was significantly lower
      compared to complicated diverticulitis (median 0.05, interquartile range [IQR]
      0.05-0.06 ng/l vs median 0.13, IQR 0.05-0.23 ng/l; p <0.0001). In the ROC
      analysis, the sensitivity and specificity were 81% and 91% when the highest
      procalcitonin value (days 1 and 2) was considered, with a cut-off value of 0.1
      ng/l. CONCLUSION: Procalcitonin was able to differentiate with a high sensitivity
      and specificity between complicated and uncomplicated cases of diverticulitis
      when combined with abdominal CT scans. As most clinicians still treat
      uncomplicated diverticulitis with antibiotics, procalcitonin could be an
      interesting parameter for guiding therapy and decreasing antibiotic usage. This
      should be further evaluated in randomised trials.

PMID- 29185247
TI  - Technical comment on: Gawinecka et al. Acute aortic dissection: pathogenesis,
      risk factors and diagnosis.

PMID- 29185248
TI  - Reply to technical comment on: Biskup E, et al. Oncological patients in the
      intensive care unit: prognosis, decision-making, therapies and end-of-life care.

PMID- 29185249
TI  - Temporal trends of postpartum haemorrhage in Switzerland: a 22-year retrospective
      population-based cohort study.
AB  - AIM: Postpartum haemorrhage (PPH) is one of the leading causes of maternal
      morbidity and mortality. Studies have reported an increase in incidence of
      postpartum haemorrhage in recent years. Our goal was to investigate changes in
      the incidence of postpartum haemorrhage (PPH) and its risk factors in Switzerland
      from 1993 to 2014. METHODS: This population-based retrospective cohort study used
      data from the national Swiss Hospital in-patient database for obstetric and
      gynaecological hospital admissions - "Arbeitsgemeinschaft Schweizer
      Frauenkliniken" (ASF Statistik). All patients with deliveries between January
      1993 and December 2014 were included. We used the database codes to identify
      patients with PPH, maternal factors, pregnancy-related and delivery-related
      factors. Significant changes in temporal trends were determined using Mantel
      Haenszel test for trend. Multivariable logistic regression analyses were
      conducted to assess PPH and risk factors. RESULTS: Births complicated by PPH in
      Switzerland increased from 2.5% in 1993 to 4.5% in 2014 (p <0.001), paralleled by
      an increase in uterine atony. Failure to progress during the second stage of
      labour (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.5-1.6), oxytocin
      augmentation (OR 1.2, 95% CI 1.2-1.3), vacuum extraction (OR 1.1, 95% CI 1.1
      1.2), and especially abnormally invasive placenta (OR 10.4, 95% CI 9.5-11.5) and
      placenta praevia (OR 4.9, 95% CI 432-5.6) were factors with the highest risk for
      postpartum haemorrhage. CONCLUSIONS: Postpartum haemorrhage is a relatively
      common and potentially dangerous obstetric complication with increasing incidence
      over the last two decades in Switzerland. Its increase over time has been
      paralleled by an increase in uterine atony.

PMID- 29185250
TI  - Management of hepatitis C in decentralised versus centralised drug substitution
      programmes and minimally invasive point-of-care tests to close gaps in the HCV
      cascade.
AB  - BACKGROUND: In Switzerland, intravenous drug use accounts for the majority of
      hepatitis C virus (HCV) infections. Early HCV treatment prevents further
      transmissions and reduces morbidity and mortality due to decompensated liver
      cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug
      substitution programmes are often insufficiently screened and treated. AIM: The
      aim was to compare the current state of HCV management in centralised and
      decentralised drug substitution programmes of the canton Aargau. Objectives were
      human immunodeficiency virus (HIV) and HCV prevalence, compliance with guidelines
      and gaps in the HCV cascade, as well as feasibility/acceptance/validity of
      HIV/HCV rapid tests on finger-prick blood and noninvasive liver fibrosis
      assessment with Fibroscan(r). METHODS: For the cross-sectional study, in June
      2013, questionnaires and free rapid tests for HIV (Determine(r)) and HCV
      (OraQuick(r)) that used capillary blood (finger-stick) were sent to 161
      physicians providing drug substitution treatment for 631 patients. Free liver
      fibrosis assessment with Fibroscan(r) by a member of the study team was offered
      to all patients. Additionally, patients were directly recruited by the study team
      in the heroin substitution programme and several addiction clinics visited every
      4-6 months, as well as in the Infectious Diseases Outpatient Clinic
      (questionnaire, rapid tests and Fibroscan(r) in the same session). RESULTS:
      Between July 2013 and July 2015, 205 (32.5%) of the 631 patients receiving opioid
      substitution in the canton Aargau were enrolled, 192 (93.7%) with HIV/HCV rapid
      tests and 167 (81.5%) with Fibroscan(r). Acceptance of Fibroscan(r) was higher
      when offered in the same session (94.1 vs 69.2%). Overall, 77.8% had ever used
      intravenous drugs. HCV seroprevalence was 53.7% (109/203), HCV RNA prevalence
      27.8%. Overall, 7.4% (15/202) were HIV infected, all of whom were HCV co-infected
      and under antiretroviral treatment. Of the 205 patients included, 104 (50.7%)
      were recruited in a decentralised setting (family practice / pharmacy) and 101
      (49.3%) in a centralised setting (heroin programme, addiction clinic, Infectious
      Diseases Outpatient Clinic). Compliance with guidelines (regular HIV/HCV
      screening, workup of HCV-positive patients, availability of HAV/HBV serology) was
      consistently lower in the decentralised setting, characterised by a higher
      proportion of females, longer median time in the programme, lower percentage of
      daily attendance, ever-use of intravenous drugs and HIV and HCV infections. We
      identified several gaps in the HCV cascade: 23.9% (49/205) had never been HCV
      screened; 18.9% (18/95) of the HCV positive patients had no HCV RNA test. Of the
      61 patients developing chronic HCV infection, 19.7% (12) were not HCV genotyped,
      52.5% (32) had no liver fibrosis assessment (liver biopsy) and 54.1% (33) never
      received treatment; 25.0% (7/28) did not achieve a sustained virological response
      with interferon-based treatment. The 192 HCV rapid tests showed a sensitivity of
      90.4% (94/104; 95% confidence interval 84.7-96.1%) and a specificity of 100%
      (88/88), and provided 14 new HCV diagnoses. Eight of ten patients with a false
      negative HCV rapid test were HCV RNA negative (2 unknown). Among the 88.6%
      (39/44) currently HCV RNA-positive individuals with valid Fibroscan(r) results,
      24 (61.5%) had a liver stiffness <7.5 kPa. Both HIV co-infection and alcohol
      overconsumption doubled the risk of severe fibrosis/cirrhosis in HCV positive
      patients. CONCLUSION: In contrast to HIV, HCV transmission among intravenous drug
      users is still ongoing. The management of hepatitis C in drug substitution
      patients needs improvement, especially in family practices. Minimally invasive
      "point-of-care" diagnostics such as the HCV antibody rapid test using capillary
      blood and mobile Fibroscan(r) can close some of the gaps in the HCV cascade. HCV
      RNA determination in capillary blood is still an unmet need. A "one-stop
      strategy" might improve linkage to care. Restricting the new, highly efficient
      (90-100% sustained virological response for all genotypes) direct-acting
      antivirals to patients with at least stage F2 fibrosis withholds treatment from
      two thirds of the chronically infected and prevents us from reaching the WHO goal
      of 80% treatment uptake necessary to eliminate hepatitis C by 2030.

PMID- 29185251
TI  - Ultrasound indications for maternal STORCH testing in pregnancy.
AB  - AIMS OF THE STUDY: Fetal abnormalities found on ultrasonography lead to a variety
      of diagnostic procedures, including a panel of serologies to detect possible
      maternal STORCH infections encompassing syphilis, Toxoplasma gondii, rubella,
      cytomegalovirus, herpes simplex, and others (human immunodeficiency virus,
      hepatitis B and C, parvovirus B19, enterovirus, varicella zoster, and Leptospira
      interrogans). The value of indiscriminate testing for infections upon the
      detection of fetal ultrasound abnormalities has been questioned. The aim of this
      study was to review the ultrasonographic abnormalities leading to maternal STORCH
      panels at the obstetrics department of a university hospital. METHODS: Laboratory
      results of all maternal STORCH tests requested after the detection of
      ultrasonographic abnormalities during a 5-year period (2008-2012) were analysed.
      The main ultrasound findings possibly caused by congenital infection were noted,
      and the outcomes of confirmed maternal and fetal infections were studied.
      RESULTS: In our study period, 392 maternal STORCH tests were performed because of
      fetal ultrasound abnormalities. The most common findings leading to STORCH
      testing were intrauterine growth restriction (30.4%) including microcephaly
      (1.5%), polyhydramnios (14.8%), and intrauterine fetal demise (13.3%). Maternal
      STORCH infections were found in 3.4% of growth-restricted fetuses, 5.2% of
      polyhydramnios, and 1.9% of intrauterine fetal demise. The leading aetiologies
      were cytomegalovirus and parvovirus B19. All seven congenital infections
      displayed multiple ultrasonographic abnormalities. CONCLUSION: Ultrasonographic
      findings associated with fetal infection are neither sensitive nor specific.
      Testing for STORCH infections should take into account exposure history, clinical
      signs and symptoms, obstetric history, and fetal ultrasound findings, but with
      special attention paid to cytomegalovirus and parvovirus B19.

PMID- 29185252
TI  - Multidrug resistant (or antimicrobial-resistant) pathogens - alternatives to new
      antibiotics?
AB  - For the last few decades, multidrug resistance has become an increasing concern
      for both Gram-positive and Gram-negative bacteria. The number of new molecules
      has dramatically decreased and antibiotic resistance is now a priority in the
      international community. Facing this new threat, a large number of new as well as
      "old" solutions are now being discussed in the medical community to propose an
      alternative to antibiotic treatments. A first option is to potentiate the effect
      of existing molecules through combinations to circumvent the individual molecule
      resistance. The second option is to neutralise either the infectious agent itself
      or its by-products using specific antibodies. A third option is to use the
      pathogen signaling mechanism and inhibit the production of virulence factor
      through quorum sensing inhibition. A fourth pathway would be to interact with the
      patient's microbiota using either probiotics or faecal transplantation to
      modulate the innate immune response and improve response to the infectious
      challenge, but also to act directly against colonisation by resistant bacteria by
      replacing the flora with susceptible strains. The last option is to target the
      bacteria using phage therapy. Phages are natural viruses that specifically infect
      target bacteria independently of any antibiotic-susceptibility profile. In this
      review, we will discuss each of these options and provide the scientific
      rationale and the available clinical data. In the majority of cases, these
      treatments represent an interesting approach but not the ultimate solution to
      multiresistance. Well-performed clinical trials are still missing and the major
      priority remains to promote good use and appropriate stewardship of antibiotics
      to decrease resistance.

PMID- 29185253
TI  - Cost-effectiveness of sacubitril/valsartan in chronic heart-failure patients with
      reduced ejection fraction.
AB  - AIMS: We aimed to assess the cost effectiveness of sacubitril/valsartan compared
      to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of
      individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from
      the perspective of the Swiss health care system. METHODS: The cost-effectiveness
      analysis was implemented as a lifelong regression-based cohort model. We compared
      sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF
      and New York-Heart Association Functional Classification II-IV symptoms.
      Regression models based on the randomised clinical phase III PARADIGM-HF trials
      were used to predict events (all-cause mortality, hospitalisations, adverse
      events and quality of life) for each treatment strategy modelled over the
      lifetime horizon, with adjustments for patient characteristics. Unit costs were
      obtained from Swiss public sources for the year 2014, and costs and effects were
      discounted by 3%. The main outcome of interest was the incremental cost
      effectiveness ratio (ICER), expressed as cost per quality-adjusted life years
      (QALYs) gained. Deterministic sensitivity analysis (DSA) and scenario and
      probabilistic sensitivity analysis (PSA) were performed. RESULTS: In the base
      case analysis, the sacubitril/valsartan strategy showed a decrease in the number
      of hospitalisations (6.0% per year absolute reduction) and lifetime hospital
      costs by 8.0% (discounted) when compared with enalapril. Sacubitril/valsartan was
      predicted to improve overall and quality-adjusted survival by 0.50 years and 0.42
      QALYs, respectively. Additional net-total costs were CHF 10 926. This led to an
      ICER of CHF 25 684. In PSA, the probability of sacubitril/valsartan being cost
      effective at thresholds of CHF 50 000 was 99.0%. CONCLUSION: The treatment of
      HFrEF patients with sacubitril/valsartan versus enalapril is cost effective, if a
      willingness-to-pay threshold of CHF 50 000 per QALY gained ratio is assumed.

PMID- 29185254
TI  - Technical comment on: Biskup E, et al. Oncological patients in the intensive care
      unit: prognosis, decision-making, therapies and end-of-life care.

PMID- 29185255
TI  - Informal caregiving, work-privacy conflict and burnout among health professionals
      in Switzerland - a cross-sectional study.
AB  - INTRODUCTION: Health professionals were found to have an elevated burnout risk
      compared to the general population. Some studies also reported more emotional
      exhaustion - a component of burnout - for health professionals with informal
      caregiving responsibilities for children (double-duty child caregivers) or adults
      (double-duty adult caregivers) or a combination of both (triple-duty caregivers)
      compared to health professionals without informal caregiving roles (formal
      caregivers). However, the potential mediating effect of the work-privacy conflict
      in this relationship as well as differences between occupational groups have not
      yet been studied in healthcare settings. AIM: To assess the impact of informal
      caregiving on burnout risk among health professionals and whether this
      relationship is mediated by work-privacy conflict or differs between occupational
      groups. METHODS: Data were collected through an employee survey in six hospitals
      from German-speaking Switzerland in 2015/2016. Mediation analyses were performed
      using linear mixed models with fixed effects for caregiving situation and work
      privacy conflict as well as random effects for hospitals. RESULTS: Triple-duty
      caregivers were found to have a significantly higher burnout risk compared to
      formal caregivers only. Work-privacy conflict did not mediate this relationship,
      except among the "other health professionals" group. CONCLUSION: Additional and
      large-scale studies focusing on the combination of formal and informal caregiving
      roles are needed to better understand its effect on burnout among healthcare
      professionals and to evaluate the role of work-privacy conflict.

PMID- 29185256
TI  - Reply to technical comment on: Gawinecka et al. Acute aortic dissection:
      pathogenesis, risk factors, diagnosis.

PMID- 29185257
TI  - Optimal mesenchymal stem cell delivery routes to enhance neurogenesis for the
      treatment of Alzheimer's disease: optimal MSCs delivery routes for the treatment
      of AD.
AB  - Alzheimer's disease (AD) is a common cause of dementia. Alzheimer's disease (AD)
      is characterized by progressive loss of memory in addition to cortical atrophy.
      Despite decades of research and therapeutic trials in AD, an effective treatment
      is yet to be developed. Mesenchymal stem cells (MSCs) have emerged as promising
      tools for the treatment of AD, and clinical trials have been completed or are in
      progress. MSCs secrete various cytotropic factors that may exert beneficial
      effects in AD. The route of administration is an important factor to enhance MSC
      based treatment effects for AD. Among various routes, the intracerebroventricular
      route may possess several advantages such as the activation of neurogenesis,
      compared to other routes for AD treatments. In this review, we will focus on
      recent pre-clinical and clinical advances in MSC-based treatment of AD,
      specifically in relation to enhancement of endogenous neurogenesis.

PMID- 29185258
TI  - Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a
      progressive or relapsing and remitting paralysing illness, probably due to an
      autoimmune response, which should benefit from corticosteroid treatment. Non
      randomised studies suggest that corticosteroids are beneficial. Two commonly used
      corticosteroids are prednisone and prednisolone. Both are usually given as oral
      tablets. Prednisone is converted into prednisolone in the liver so that the
      effect of the two drugs is usually the same. Another corticosteroid,
      dexamethasone, is more potent and is used in smaller doses. The review was first
      published in 2001 and last updated in 2015; we undertook this update to identify
      any new evidence. OBJECTIVES: To assess the effects of corticosteroid treatment
      for CIDP compared to placebo or no treatment, and to compare the effects of
      different corticosteroid regimens. SEARCH METHODS: On 8 November 2016, we
      searched the Cochrane Neuromuscular Specialised Register, Cochrane Central
      Register of Controlled Trials, MEDLINE, and Embase for randomised trials of
      corticosteroids for CIDP. We searched clinical trials registries for ongoing
      trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or
      quasi-RCTs of treatment with any corticosteroid or adrenocorticotrophic hormone
      for CIDP, diagnosed by an internationally accepted definition. DATA COLLECTION
      AND ANALYSIS: Two authors extracted data from included studies and assessed the
      risk of bias independently. The intended primary outcome was change in
      disability, with change in impairment after 12 weeks and side effects as
      secondary outcomes. We assessed strength of evidence using the GRADE approach.
      MAIN RESULTS: One non-blinded RCT comparing prednisone with no treatment in 35
      eligible participants did not measure the primary outcome for this systematic
      review. The trial had a high risk of bias. Neuropathy Impairment Scale scores
      after 12 weeks improved in 12 of 19 participants randomised to prednisone,
      compared with five of 16 participants randomised to no treatment (risk ratio (RR)
      for improvement 2.02 (95% confidence interval (CI) 0.90 to 4.52; very low-quality
      evidence). The trial did not report side effects in detail, but one prednisone
      treated participant died.A double-blind RCT comparing daily standard-dose oral
      prednisolone with monthly high-dose oral dexamethasone in 40 participants
      reported none of the prespecified outcomes for this review. The trial had a low
      risk of bias, but the quality of evidence was limited as it came from a single
      small study. There was little or no difference in number of participants who
      achieved remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly
      dexamethasone; moderate-quality evidence), or change in disability or impairment
      after one year (low-quality evidence). Change of grip strength or Medical
      Research Council (MRC) scores demonstrated little or no difference between groups
      (moderate-quality to low-quality evidence). Eight of 16 people in the
      prednisolone group and seven of 24 people in the dexamethasone group
      deteriorated. Side effects were similar with each regimen, except that
      sleeplessness was less common with monthly dexamethasone (low-quality evidence)
      as was moon facies (moon-shaped appearance of the face) (moderate-quality
      evidence).Experience from large non-randomised studies suggests that
      corticosteroids are beneficial, but long-term use causes serious side effects.
      AUTHORS' CONCLUSIONS: We are very uncertain about the effects of oral prednisone
      compared with no treatment, because the quality of evidence from the only RCT
      that exists is very low. Nevertheless, corticosteroids are commonly used in
      practice, supported by very low-quality evidence from observational studies. We
      also know from observational studies that corticosteroids carry the long-term
      risk of serious side effects. The efficacy of high-dose monthly oral
      dexamethasone is probably little different from that of daily standard-dose oral
      prednisolone. Most side effects occurred with similar frequencies in both groups,
      but with high-dose monthly oral dexamethasone moon facies is probably less common
      and sleeplessness may be less common than with oral prednisolone. We need further
      research to identify factors that predict response.

PMID- 29185260
TI  - Robotic single site radical hysterectomy plus pelvic lymphadenectomy in
      gynecological cancers.
AB  - OBJECTIVE: To evaluate the feasibility and the safety of robotic single-site
      radical hysterectomy (RSSRH) plus pelvic lymphadenectomy (PL) in endometrial or
      cervical cancer. METHODS: Patients with endometrial cancer (EC) International
      Federation of Gynecology and Obstetrics (FIGO) stage II, early cervical cancer
      (ECC) FIGO stage IB1 or locally advanced cervical cancer (LACC) FIGO stage IB2
      IIB with clinical response >=50% after neo-adjuvant chemotherapy (NACT) were
      enrolled in a prospective cohort trial. All cases were performed using the da
      Vinci Si Surgical Single Site System(r). RESULTS: Between April 2014 and November
      2016, twenty patients were included in our pilot study. Three and 17 patients
      underwent type B1 or C1 RSSRH plus PL, respectively. The median age of patients
      was 46 years (range, 36-68 years) and the median body mass index was 23.5 kg/m2
      (range, 19.1-36.3 kg/m2). The median total operative time was 190 minutes (range,
      90-310 minutes). The median blood loss was 75 mL (range, 20-700 mL) and the
      median number of pelvic lymph nodes removed was 16 (range, 5-27). No
      laparoscopic/laparotomic conversions were reported and the median time to
      discharge was 6 days (range, 4-16 days). No intra-operative complications
      occurred while 4 (20%) post-operative complications were reported: one pelvic
      abscess, one lymphorrea, one bowel perforation, and one vaginal dehiscence.
      CONCLUSION: RSSRH plus PL is technically feasible in patients affected by
      gynecological cancer.

PMID- 29185259
TI  - Role of lymphadenectomy in intermediate-risk endometrial cancer: a matched-pair
      study.
AB  - OBJECTIVE: To assess the impact of lymph node dissection (LND) on morbidity,
      survival, and cost for intermediate-risk endometrial cancers (IREC). METHODS: A
      multicenter retrospective cohort of 720 women with IREC (endometrioid histology
      with myometrial invasion <50% and grade 3; or myometrial invasion >=50% and
      grades 1-2; or cervical involvement and grades 1-2) was carried out. All patients
      underwent hysterectomy and bilateral salpingo-oophorectomy. A matched pair
      analysis identified 178 pairs (178 with LND and 178 without it) equal in age,
      body mass index, co-morbidities, American Society of Anesthesiologist score,
      myometrial invasion, and surgical approach. Demographic data, pathology results,
      perioperative morbidity, and survival were abstracted from medical records.
      Disease-free survival (DFS) and overall survival (OS) was analyzed using Kaplan
      Meier curves and multivariate Cox regression analysis. Cost analysis was carried
      out between both groups. RESULTS: Both study groups were homogeneous in
      demographic data and pathologic results. The mean follow-up in patients free of
      disease was 61.7 months (range, 12.0-275.5). DFS (hazard ratio [HR]=1.34; 95%
      confidence interval [CI]=0.79-2.28) and OS (HR=0.72; 95% CI=0.42-1.23) were
      similar in both groups, independently of nodes count. In LND group, positive
      nodes were found in 10 cases (5.6%). Operating time and late postoperative
      complications were higher in LND group (p<0.05). Infection rate was significantly
      higher in no-LND group (p=0.035). There were no statistical differences between
      both groups regarding operative morbidity and hospital stay. The global cost was
      similar for both groups. CONCLUSION: Systematic LND in IREC has no benefit on
      survival, although it does not show an increase in perioperative morbidity or
      global cost.

PMID- 29185261
TI  - Pazopanib monotherapy in the treatment of pretreated, metastatic uterine sarcoma:
      a single-center retrospective study.
AB  - OBJECTIVE: In the treatment of metastatic soft tissue sarcoma (STS), pazopanib is
      considered a standard treatment after failure of chemotherapy. We retrospectively
      investigated outcomes of pazopanib in patients with metastatic uterine STS.
      METHODS: A retrospective study was performed on 35 consecutive patients with
      uterine STS treated with oral pazopanib 800 mg daily as salvage therapy for
      metastatic disease between September 2013 and December 2015. Endpoints included
      response rate, survival, and safety. RESULTS: Among 35 patients, 27 (77%) had a
      histologic diagnosis of leiomyosarcoma (LMS) and the median age was 57 years
      (range, 36-70). Median number of metastatic sites was one (range, 1-5) with lung
      as the most frequently involved site. Pazopanib was generally well-tolerated: the
      major hematologic toxicity was grade 1/2 anemia (14%). Among the non-hematologic
      toxicities, grade 1/2 stomatitis was most commonly observed (22%), followed by
      fatigue and hypertension. Objective response and stable disease were observed in
      10 (29%) and 11 (31%) patients, respectively. However, most cases of clinical
      response were observed in patients with LMS: 33% for LMS, 20% for
      undifferentiated pleomorphic sarcoma, and 0% for endometrial stromal sarcoma.
      Median progression-free and overall survivals were 5.8 months (95% confidence
      interval [CI]=3.6-8.1) and 20.0 months (95% CI=11.6-28.4), respectively.
      CONCLUSION: In this "real-world" retrospective study, salvage therapy with
      pazopanib demonstrated clinically relevant efficacy and tolerability in
      unselected patients with uterine STS. Although it is encouraging that outcomes
      for Korean patients with uterine STS were similar to those reported in the phase
      III trial, the clinical benefit was limited to LMS.

PMID- 29185262
TI  - Mutational analysis of KRAS and its clinical implications in cervical cancer
      patients.
AB  - OBJECTIVE: The predictive and prognostic role of KRAS mutations in cervical
      cancer remains inconclusive. The aim of this study was to explore the
      clinicopathological and prognostic relevance of KRAS mutations in invasive
      cervical cancers (ICC). METHODS: Reverse transcription polymerase chain reaction
      (PCR) and Sanger sequencing were employed to detect KRAS mutations in 876 ICC
      patients. Quantitative real-time PCR was used to detect human papillomavirus
      (HPV) 16 and HPV 18. RESULTS: Non-synonymous mutations of KRAS were identified in
      30 (3.4%) patients. These mutations were more common in non-squamous cell
      carcinoma than in squamous cell carcinoma (SCC) (8.2% vs. 2.2%, respectively,
      p<0.001) and were associated with HPV 18 infection (p=0.003). The prevalence of
      mutations was highest (18.2%) in the uncommon histological subtypes followed by
      adenocarcinoma (AC, 7.3%) and adenosquamous carcinoma (ASC, 5.8%). During the
      median follow-up of 55 months, compared to patients with wild-type KRAS, a
      greater percentage of patients with mutant KRAS relapsed (20.0% vs. 42.9%,
      respectively, p=0.007). The 3-year relapse-free survival was poorer in patients
      with mutant KRAS than in patients without KRAS mutations (57.1% vs. 81.9%,
      respectively, p=0.001). Furthermore, the multivariate analysis showed that the
      presence of a KRAS mutation was an independent predictor for disease recurrence
      (hazard ratio [HR]=2.064; 95% confidence interval [CI]=1.125-3.787; p=0.019).
      CONCLUSION: KRAS mutations were predominant in non-SCCs of the cervix and were
      associated with HPV 18 infection. A combination of KRAS mutation detection and
      HPV genotyping would be useful in identifying patient with poor prognosis for
      further interventions.

PMID- 29185263
TI  - Oncologic outcomes of adjuvant chemotherapy alone after radical surgery for stage
      IB-IIA cervical cancer patients.
AB  - OBJECTIVE: To evaluate the oncologic outcomes of adjuvant chemotherapy (CT) alone
      after radical surgery. METHODS: We retrospectively reviewed the medical records
      of patients who underwent type C radical hysterectomy and pelvic lymphadenectomy
      with or without paraaortic lymphadenectomy for stage IB-IIA cervical cancer from
      March 2006 to December 2014 at 2 academic medical centers in Korea. Adjuvant CT
      alone for patients who met the Sedlis criteria or had lymph node (LN)
      involvement. Chemotherapeutic regimens consisted of either platinum alone or
      platinum-based combination. RESULTS: A total of 101 consecutive patients were
      included in the analysis. The median age was 46.0 years (range, 23-73). Seventy
      four patients (73.3%) were clinically staged as IB1; 23 and 4 patients as IB2 and
      IIA, respectively. The median number of retrieved pelvic and paraaortic LNs
      (PALNs) were 55.0 (range, 16-101) and 10.0 (range, 2-30), respectively. LN
      involvement was observed in 25 patients (24.8%). After the median follow-up of 65
      months, 14 patients (13.9%) developed disease recurrence. In all patients, the
      estimated 3-year disease-free survival (DFS) rate and 5-year overall survival
      (OS) rate were 90.7% and 90.6%, respectively. In patients who met the Sedlis
      criteria, the 3-year DFS and 5-year OS rates were 94.6% and 90.6%, respectively.
      Patients with LN metastasis showed a 3-year DFS rate of 79.4% and a 5-year OS
      rate of 90.6%. CONCLUSION: Adjuvant CT alone could be reasonable option for
      patients with surgical-pathologic risk factors after radical surgery in stage IB
      IIA cervical cancer.

PMID- 29185264
TI  - Clinical outcomes and risk of recurrence among patients with vaginal
      intraepithelial neoplasia: a comprehensive analysis of 576 cases.
AB  - OBJECTIVE: To evaluate the clinical outcomes of vaginal intraepithelial neoplasia
      (VAIN) and to assess the risk of recurrence and progression to invasive vaginal
      carcinoma. METHODS: A retrospective review of the clinicopathologic data and
      clinical outcomes was performed on patients who were diagnosed with VAIN at a
      single center between January 2000 and July 2016. Demographics, treatments, and
      clinical outcomes were abstracted from medical records. RESULTS: A total of 576
      patients with VAIN1-3 were included in the study analysis. The distribution of
      VAIN1-3 was as follows: VAIN1 31.1%, VAIN2 45.3%, and VAIN3/carcinoma in situ
      (CIS) 23.6%. In VAIN1 patients, observation was performed in 29.1% of the cases
      and 48.8% obtained regression. In VAIN2+ patients, management included
      observation (3.5%), topical management (6.5%), laser ablation (75.3%), excision
      (14.1%), and radiotherapy (0.5%) with the following rates of
      recurrence/progression: 46.2%, 62.5%, 26.4%, 32.7%, and 0%, respectively. Four
      patients among VAIN3/CIS patients (3.2%) developed invasive vaginal cancer during
      the follow-up period with a median time to cancer diagnosis of 21.4 months
      (range, 5.0-44.8 months). On multivariate analysis, high-risk human
      papillomavirus (HPV) positivity and treatment method were found to be independent
      risk factors for recurrence and progression (p=0.003 and p=0.001). CONCLUSION:
      Patients with VAIN are at high-risk of recurrence, but the risk of progression to
      vaginal cancer is relatively low. Laser or excision provides higher regression
      rate than topical agent or observation, and high-risk HPV positivity is a risk
      factor for recurrence. Whatever the treatment method is used, however, the high
      rate of recurrence warrants long-term follow-up surveillance.

PMID- 29185265
TI  - Epidemiology of gynecologic cancers in China.
AB  - Cancer has become a major disease burden across the globe. It was estimated that
      4.29 million new incident cases and 2.81 million death cases of cancer would
      occur in 2015 in China, with the age-standardized incidence rate (ASIR) of 201.1
      per 100,000 and age-standardized mortality rate (ASMR) of 126.9 per 100,000,
      respectively. For females, 2 of the top 10 most common types of cancer would be
      gynecologic cancers, with breast cancer being the most prevalent (268.6 thousand
      new incident cases) and cervical cancer being the 7th most common cancer (98.9
      thousand new incident cases). The incidence and mortality of gynecologic cancers
      have been constantly increasing in China over last 2 decades, which become a
      major health concern for women. Survival rates of gynecologic cancers are
      generally not satisfactory and decrease along with advancing stage, though
      national data on survival are still not available. It is of great importance to
      overview on the epidemiology of gynecologic cancers, which may provide scientific
      clues for strategy-making of prevention and control, and eventually lowering the
      incidence and mortality rate as well as improving the survival rate in the
      future.

PMID- 29185266
TI  - Are vaginal swabs comparable to cervical smears for human papillomavirus DNA
      testing?
AB  - OBJECTIVE: Human papillomavirus (HPV) testing is widely incorporated into
      cervical cancer screening strategies. Current screening requires pelvic
      examination for cervical sampling, which may compromise participation. The
      acceptance could be raised by introducing testing on vaginal swabs. We explored
      the interchangeability of vaginal swabs and cervical smears for HPV testing, by
      means of a prospective study conducted in female sex workers (FSWs). Besides, we
      report on the occurrence of 32 different HPV genotypes in FSW with low-grade
      squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial
      lesion (HSIL). METHODS: Paired physician-collected vaginal swabs and cervical
      smears from 303 FSW were tested for HPV using the Abbott RealTime High-Risk HPV
      assay. Cervical cytology was examined on cervical smears. In case of HSIL/LSIL
      cytological classification (n=52), both samples were genotyped using INNO-LiPa
      HPV Genotyping Extra II. RESULTS: The overall prevalence of high-risk (HR)-HPV
      was 51%. In FSW with HSIL/LSIL cervical cytology, the sensitivity and specificity
      of vaginal samples for the detection of HR-HPV was 100% and 70% and for probable
      HR-HPV 100% and 91%. The mean number of genotypes identified in vaginal samples
      (mean=3.5; 95% confidence interval [CI]=2.8-4.2) was significantly higher than in
      cervical smear samples (mean=2.6; 95% CI=2.1-3.0) (p=0.001). The most frequently
      encountered HR-HPV genotypes were HPV16, 31, 51, and 52. CONCLUSION: As our study
      shows that vaginal swabs are equivalent to cervical smears for the detection of
      (probable) HR-HPV, vaginal swabs can be used for HPV testing in cervical cancer
      screening strategies. Given the acceptance of vaginal sampling, this finding
      offers an opportunity to boost screening coverage.

PMID- 29185267
TI  - Baseline risk of recurrence in stage I-II endometrial carcinoma.
AB  - OBJECTIVE: Though there are no evidences that postoperative therapy improves
      overall survival (OS) in stage I-II endometrial carcinoma, many women receive
      postoperative radiation or chemotherapy. This study aimed to investigate the
      baseline risk of recurrence after complete resection without any adjuvant
      therapies and to suppose the validity of postoperative therapy for stage I-II
      endometrial carcinoma. METHODS: Charts for patients with stage I-II endometrial
      carcinoma who underwent operation without postoperative therapy between January
      2005 and December 2011 were retrospectively reviewed and the baseline risk of
      recurrence and prognosis were assessed. Risk classifications were performed
      according to European Society for Medical Oncology (ESMO) clinical practice
      guidelines and Japanese guideline written by Japan Society of Gynecologic
      Oncology Group. RESULTS: Among 374 patients who underwent complete resection, 311
      were evaluable. Five-year recurrence rates by ESMO and Japanese were 2.6% and
      3.1% in low-risk, 9.2% and 6.6% in intermediate-risk and 13.5% and 13.8% in high
      risk group (p=0.003 and 0.015, respectively). High-risk group had worse OS
      compared with low- and intermediate-risk groups (5-year OS, low: 97.9% and 97.6%,
      intermediate: 97.9% and 98.8%, and high: 89.5% and 87.5%; p=0.003 and 0.008,
      respectively). Independent predictive factors of recurrence were age over 60
      years, type 2 (estrogen-independent) and peritoneal cytology. CONCLUSION: ESMO
      and Japanese risk classification similarly stratify the baseline risk of
      recurrence. Patients with stage I-II endometrial carcinoma, especially low- and
      intermediate-risk diseases, have low recurrence rate and favorable OS, and the
      benefit of postoperative therapy might be small.

PMID- 29185268
TI  - Quality and quantity metrics of pelvic lymph node metastasis and risk of para
      aortic lymph node metastasis in stage IB-IIB cervical cancer.

PMID- 29185269
TI  - Risk stratification models for para-aortic lymph node metastasis and recurrence
      in stage IB-IIB cervical cancer.
AB  - OBJECTIVE: To examine the surgical-pathological predictors of para-aortic lymph
      node (PAN) metastasis at radical hysterectomy, and for PAN recurrence among women
      who did not undergo PAN dissection at radical hysterectomy. METHODS: This is a
      retrospective analysis of a nation-wide cohort study of surgically-treated stage
      IB-IIB cervical cancer (n=5,620). Multivariate models were used to identify
      independent surgical-pathological predictors for PAN metastasis/recurrence.
      RESULTS: There were 120 (2.1%) cases of PAN metastasis at surgery with
      parametrial involvement (adjusted odds ratio [aOR]=1.65), deep stromal invasion
      (aOR=2.61), ovarian metastasis (aOR=3.10), and pelvic nodal metastasis (single
      node aOR=5.39 and multiple-node aOR=33.5, respectively) being independent risk
      factors (all, p<0.05). Without any risk factors, the incidence of PAN metastasis
      was 0.9%, while women exhibiting certain risk factor patterns (>20% of the study
      population) had PAN metastasis incidences of >=4%. Among 4,663 clinically PAN
      negative cases at surgery, PAN recurrence was seen in 195 (4.2%) cases that was
      significantly higher than histologically PAN-negative cases (2.5%, p=0.046). In
      clinically PAN-negative cases, parametrial involvement (adjusted hazard ratio
      [aHR]=1.67), lympho-vascular space invasion (aHR=1.95), ovarian metastasis
      (aHR=2.60), and pelvic lymph node metastasis (single-node aHR=2.49 and multiple
      node aHR=8.11, respectively) were independently associated with increased risk of
      PAN recurrence (all, p<0.05). Without any risk factors, 5-year PAN recurrence
      risk was 0.8%; however, women demonstrating certain risk factor patterns (>15% of
      the clinically PAN-negative population) had 5-year PAN recurrence risks being
      >=8%. CONCLUSION: Surgical-pathological risk factors proposed in this study will
      be useful to identify women with increased risk of PAN metastasis/recurrence.

PMID- 29185270
TI  - Impact of lymph node ratio on survival in stage III ovarian high-grade serous
      cancer: a Turkish Gynecologic Oncology Group study.
AB  - OBJECTIVE: The purpose of this study was to investigate the prognostic value of
      lymph node ratio (LNR) in patients with stage III ovarian high-grade serous
      carcinoma (HGSC). METHODS: A multicenter, retrospective department database
      review was performed to identify patients with ovarian HGSC at 6 gynecologic
      oncology centers in Turkey. A total of 229 node-positive women with stage III
      ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus
      systematic lymphadenectomy followed by paclitaxel plus carboplatin combination
      chemotherapy were included. LNR, defined as the percentage of positive lymph
      nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%),
      LNR2 (10%<=LNR<50%), and LNR3 (>=50%). Kaplan-Meier method was used to generate
      survival data. Factors predictive of outcome were analyzed using Cox proportional
      hazards models. RESULTS: Thirty-one women (13.6%) were classified as stage IIIA1,
      15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at
      diagnosis was 56 (range, 18-87), and the median duration of follow-up was 36
      months (range, 1-120 months). For the entire cohort, the 5-year overall survival
      (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from
      65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In
      multivariate analysis, women with LNR>=0.50 were 2.7 times more likely to die of
      their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42-5.18;
      p<0.001). CONCLUSION: LNR seems to be an independent prognostic factor for
      decreased OS in stage III ovarian HGSC patients.

PMID- 29185271
TI  - Prognostic significance of normal-sized ovary in advanced serous epithelial
      ovarian cancer.
AB  - OBJECTIVE: We compared survival outcomes of advanced serous type epithelial
      ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian
      tumors by propensity score matching analysis. METHODS: The medical records of EOC
      patients treated at Samsung Medical Center between 2002 and 2015 were reviewed
      retrospectively. We investigated EOC patients with high grade serous type
      histology and International Federation of Gynecology and Obstetrics (FIGO) stage
      IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant
      chemotherapy to identify patients with normal-sized ovaries. Propensity score
      matching was performed to compare patients with normal-sized ovaries to patients
      with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial
      cancer antigen (CA)-125 level, and residual disease status after PDS. RESULTS: Of
      the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged
      ovarian tumor were younger (54.0+/-10.3 vs. 58.4+/-9.2 years, p=0.005) than those
      with normal-sized ovary, and there was a statistically significant difference in
      residual disease status between the 2 groups. In total cohort with a median
      follow-up period of 43 months (range, 3-164 months), inferior overall survival
      (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months;
      p=0.003). After propensity score matching, the group with normal-sized ovary
      showed inferior OS compared to the group with enlarged-ovarian tumor (median OS,
      72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized
      ovary remained a significant factor. CONCLUSION: Normal-sized ovary was
      associated with poor OS compared with the common presentation of enlarged ovaries
      in EOC, independent of CA-125 level or residual disease.

PMID- 29185273
TI  - Trends of low-grade serous ovarian carcinoma in the United States.

PMID- 29185272
TI  - Prevalence of human papillomavirus genotypes and precancerous cervical lesions in
      a screening population in the Republic of Korea, 2014-2016.
AB  - OBJECTIVE: Knowledge regarding the prevalence and distribution of human
      papillomavirus (HPV) genotyping in healthy women is important in establishing
      strategies for cervical cancer screening and HPV vaccination. METHODS: A total of
      18,170 women who visited a Korean Medical Institute for health check-ups were
      recruited retrospectively; they underwent HPV genotyping and conventional
      cervical cytology. An HPV DNA test was performed using the AnyplexTM II HPV 28
      detection system (Seegene) or HPV Liquid Bead Microarray (Osang Healthcare). The
      distribution of HPV genotypes was assessed according to cervical cytology and
      age. RESULTS: HPV was detected in 3,037 (16.71%) of the 18,170 women enrolled,
      and 2,268 (12.48%) were positive for high-risk (HR) HPV. In total, HPV 53 (9.69%
      of all detected HPV viruses) was the most common type; HPV 58 (7.90%) and 52
      (7.81%) were also common. HPV 54 (6.99%) was common in low-risk subjects. Overall
      and in the normal cytology group, the most common HPV genotype was HPV 53,
      whereas HPV 58 was more common in women who had atypical squamous cells of
      undetermined significance or low-grade squamous intraepithelial neoplasia
      cervical cytology. In addition, HPV 16 was the most common type in cases with
      high-grade squamous intraepithelial neoplasia (HSIL)/atypical squamous cells
      cannot exclude HSIL. Among women with normal cytology, 76 of 231 (32.9%) women
      under 24 years of age were positive for HR HPV, whereas 84 of 852 (9.9%) women
      aged 55-59 years were positive. CONCLUSION: HPV 53 was the most prevalent
      genotype in healthy women. Distribution of HPV genotypes varied with cervical
      cytology and age. Our study provides important baseline data for the recently
      implemented national HPV vaccination program.

PMID- 29185276
TI  - Harnessing Imaging to Improve Diagnosis and Treatment of Rheumatic Diseases.

PMID- 29185274
TI  - Survival benefit of patients with early-stage ovarian carcinoma treated with
      paclitaxel chemotherapeutic regimens.
AB  - OBJECTIVE: Adjuvant chemotherapy was introduced in patients with early-stage
      ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including
      taxane has not been established. METHODS: Patients with early-stage OC from the
      National Health Insurance Research database of Taiwan who received platinum plus
      cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3-6 cycles were
      recruited, and the disease-free survival (DFS) and overall survival (OS) were
      determined. RESULTS: A total of 1,510 early-stage OC patients, including 841 who
      received CP regimen and 699 who received PT regimen, were included. The 2 groups
      had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%;
      p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who
      received the CP regimen had a lower 5-year DFS than the patients <=50 years of
      age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally,
      patients >50 years of age who received the CP regimen had a worse 5-year OS
      compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age
      in the PT group; p=0.002 for patients <=50 years of age in the CP group; and
      p=0.061 for patients <=50 years of age in the PT group). Patients with the CP or
      PT regimen for 3-5 cycles had a similar 5-year DFS and OS compared to 6 cycles
      (p>0.050). CONCLUSION: Chemotherapeutic regimens with taxane could be recommended
      for early-stage OC patients >50 years of age.

PMID- 29185277
TI  - MRI Findings of the Sacroiliac Joints in Patients with Low Back Pain: Alternative
      Diagnosis to Inflammatory Sacroiliitis.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is the most sensitive imaging
      modality for the detection of sacroiliitis. Diagnosing sacroiliitis on MRI is not
      always straightforward and can be challenging in some cases. OBJECTIVES: To
      evaluate the prevalence of alternative diagnoses suggested by MRI and
      characterize the MR appearance of the most common ones. METHODS: Consecutive MRI
      examinations of the sacroiliac joints (SIJ) performed between 2005 and 2012 were
      retrospectively evaluated for the presence of structural and active sacroiliitis
      findings according to the Assessment of SpondyloArthritis International Society
      guidelines. Alternative diagnoses, including degenerative changes, diffuse
      idiopathic skeletal hyperostosis (DISH), Osteitis condensans ilii (OCI), septic
      sacroiliitis/discitis, stress reaction as well as anatomic variants, were
      registered. RESULTS: We evaluated 281 MRI examinations, 116 males, 165 females,
      average age 44 +/- 15 years. Sacroiliitis was found in 71 examinations (25%) and
      alternative diagnoses were suggested in 87 (31%) (OCI 8.9%, anatomic variants
      5.3%, septic sacroiliitis 5.3%, degenerative findings 4.3%, diffuse idiopathic
      skeletal hyperostosis [DISH] 1.5%, stress reaction 0.7%, tumor 0.3%). A normal
      examination was found in the remaining 123 examinations. Patients with
      alternative diagnoses were older than those with sacroiliitis (62 vs. 47 years of
      age, respectively, P > 0.05). Alternative pathologies in the SIJ were
      significantly more common in females (66) than males (21), P < 0.05. CONCLUSIONS:
      A substantial proportion of patients with suspected sacroiliitis had normal SIJ
      while the rest were more commonly diagnosed with other pathologies. A referral by
      an experienced rheumatologist may improve the sensitivity and specificity of this
      important examination.

PMID- 29185275
TI  - The feasibility of detecting endometrial and ovarian cancer using DNA methylation
      biomarkers in cervical scrapings.
AB  - OBJECTIVE: We hypothesized that DNA methylation of development-related genes may
      occur in endometrial cancer (EC)/ovarian cancer (OC) and may be detected in
      cervical scrapings. METHODS: We tested methylation status by quantitative
      methylation-specific polymerase chain reaction for 14 genes in DNA pools of
      endometrial and OC tissues. Tissues of EC/normal endometrium, OC/normal ovary,
      were verified in training set using cervical scrapings of 10 EC/10 OC patients
      and 10 controls, and further validated in the testing set using independent
      cervical scrapings in 30 EC/30 OC patients and 30 controls. We generated cutoff
      values of methylation index (M-index) from cervical scrapings to distinguish
      between cancer patients and control. Sensitivity/specificity of DNA methylation
      biomarkers in detecting EC and OC was calculated. RESULTS: Of 14 genes, 4 (PTGDR,
      HS3ST2, POU4F3, MAGI2) showed hypermethylation in EC and OC tissues, and were
      verified in training set. POU4F3 and MAGI2 exhibited hypermethylation in training
      set were validated in independent cases. The mean M-index of POU4F3 is 78.28 in
      EC and 20.36 in OC, which are higher than that in controls (6.59; p<0.001 and
      p=0.100, respectively), and that of MAGI2 is 246.0 in EC and 12.2 in OC, which is
      significantly higher that than in controls (2.85; p<0.001 and p=0.480,
      respectively). Sensitivity and specificity of POU4F3/MAGI2 were 83%-90% and 69%
      75% for detection of EC, and 61% and 62%-69% for the detection of OC. CONCLUSION:
      The findings demonstrate the potential of EC/OC detection through testing for DNA
      methylation in cervical scrapings.

PMID- 29185278
TI  - Styloid Process Elongation on Cervical Spine Computed Tomography is Associated
      with the Enthesopathy-Related Diseases of Ankylosing Spondylitis and Diffuse
      Idiopathic Skeletal Hyperostosis.
AB  - BACKGROUND: Enthesopathy may lead to calcification of the stylohyoid ligament and
      can cause elongation of the styloid process (SP). OBJECTIVES: To evaluate whether
      SP elongation is associated with two common enthesitis-related diseases:
      ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH).
      METHODS: Cervical spine computed tomography (CT) examinations of patients with
      DISH (n=64, Resnick criteria), AS (n=24, New York criteria) and a controls (no
      radiological signs of DISH or AS, n=54) were retrospectively evaluated. The DISH
      group was further divided into patients with and without cervical DISH. The
      length of right and left SP was measured independently by two readers on coronal
      and sagittal curved reformats. The average right and left styloid length and
      average length per person were compared among the groups. RESULTS: Demographic
      characteristics were similar between the DISH and control groups (average age
      68.2 +/- 15.7, 69.2 +/- 12.7 years, male:female ratio 48:16 and 35:19,
      respectively, P > 0.05), whereas age was significantly lower (average age: 53 +/-
      15 years, P < 0.0001) in the AS group, which was also composed mainly of men. The
      AS and DISH groups had significantly longer SP compared to controls (AS 37.9 +/-
      9.6 mm, DISH 34.4 +/- 9 mm, control 30.3 +/- 10.1 mm, P < 0.05). There was no
      correlation between age and SP length. Inter-reader reliability of SP
      measurements was excellent in all groups (ICC = 0.998, P < 0.0001). CONCLUSIONS:
      SP elongation is associated with both AS and DISH substantiating the enthesopathy
      related pathophysiology of this finding.

PMID- 29185279
TI  - Metal-on-Metal Hip Replacement: MRI Signal Intensities of Different Body Tissues
      and Their Relations to Blood Metal Ion Levels.
AB  - BACKGROUND: Metal-on-metal total hip prostheses (MoM-THR) have been shown to
      produce hypersensitivity reactions and fluid collection (pseudotumor) by the hip
      as well as high blood metal ions levels (BMILs). OBJECTIVES: To evaluate the
      magnetic resonance imaging (MRI) signal-to-noise ratio (S/N) in selected body
      tissues around the hip of patients who underwent MoM hip replacement and to
      correlate to BMILs. METHODS: Sixty-one MRI hip examinations in 54 post-MoM-THR
      patients (18 males, 36 females, mean age 65 years) were retrospectively evaluated
      independently by two readers. The mean S/N ratio in a region of interest was
      calculated for periprosthetic pseudotumor collection (PPC), the bladder, fat, and
      muscle on axial T1w, FSE-T2w, and short tau inversion recovery (STIR) sequences
      on the same location. BMILs were retrieved from patient files. RESULTS: PPC was
      detected in 32 patients (52%) with an average volume of 82.48 mm3. BMIL did not
      correlate with the presence of PPCs but positively correlated with the PPC's
      volume. A trend for positive correlation was found between BMILs and S/N levels
      of STIR images for muscle and bladder as well as for PPC and cobalt levels. A
      trend for correlation was also seen between BMIL with PPC's T1 w S/N.
      CONCLUSIONS: Alteration of MRI S/N for different hip tissues showed a tendency
      for correlation with BMILs, possibly suggesting that metal deposition occurs in
      the PPC as well as in the surrounding tissues and bladder.

PMID- 29185280
TI  - The PET-CT Radiological Appearance of Facial Cosmetic Injections: A Pitfall in
      the Evaluation of the Oncological Patient.
AB  - BACKGROUND: Facial rejuvenation using different dermal and sub-dermal injectable
      compounds is a popular cosmetic procedure which may pose a diagnostic dilemma to
      the radiologist. OBJECTIVES: To describe the appearance of cosmetic facial
      fillers on PET-CT. METHODS: All PET-CT exams performed between January 2015 and
      May 2017 in which findings suggestive of prior facial filler procedures was
      evident and where anamnestic confirmation with the patient was possible were
      reviewed. RESULTS: We describe five females who had undergone facial filler
      procedures leading to calcifications around the mouth and nasolabial triangle.
      CONCLUSIONS: Familiarity with the appearance of such cosmetic procedures on PET
      CT is of paramount importance in order to avoid misinterpretation of the findings
      leading to unnecessary apprehension and work-up.

PMID- 29185281
TI  - Ankylosing Spondylitis and Neck Pain: MRI Evidence for Joint and Entheses
      Inflammation at the Craniocervial Junction.
AB  - BACKGROUND: Magnetic resonance imaging (MRI), which has recently become the
      leading imaging modality in the study of ankylosing spondylitis (AS), has not
      been evaluated in the assessment of disease-specific changes at the
      craniocervical junction (CCJ) in patients with AS. OBJECTIVES: To describe the
      spectrum of active inflammatory lesions at the CCJ using MRI in a cohort of
      patients with AS and neck pain. METHODS: The study included 18 patients with AS
      presenting with neck pain and a control group of 9 fibromyalgia patients matched
      for age and levels of neck pain. All patients underwent a focused rheumatologic
      examination, X-ray of the cervical spine, and a 3T MRI study, which included
      STIR, CUBE T2, FSE and FSE FAT SAT sequences before and after administration of
      gadolinium. RESULTS: The median age of AS patients was 43 years with a median
      disease duration of 7 years. Fifteen of 18 patients were under biologic
      treatment. Seven of 18 AS patients had evidence of cervical syndesmophytes on X
      ray films. Active inflammatory lesions of atlanto-occipital joints and apical and
      alar ligaments were detected in MRIs in 2 out of the 18 patients with AS and in
      none of the patients with fibromyalgia. Both AS patients with active inflammation
      of CCJ detected on MRI received treatment with biological agents prior to and
      during the study. CONCLUSIONS: Active inflammation of both entheses and joints of
      the CCJ can be demonstrated by MRI in patients with AS.

PMID- 29185282
TI  - The Lived Experience of Parkinson's Disease: A Content Analysis of Parkinson's
      Patients' Blogs.
AB  - BACKGROUND: Blogs have become a major venue of information sharing and emotional
      release for people worldwide. Illness blogs are a specific type of blog in which
      patients describe their experience with illness and coping with disease. Illness
      blog research has been conducted on several disorders; however, blogs by
      Parkinson's disease (PD) patients have been neglected. OBJECTIVES: To categorize
      the characteristics of PD patients from blogs and explore whether we can learn
      about the medical issues with which they are most concerned, as conveyed through
      their blog posts. METHODS: Using located PD patients' blogs, we analyzed the
      contents of 78 blogs, and employed thematic analysis of eight arbitrarily
      selected blogs. RESULTS: The majority of blog authors in our sample (N=78) were
      from the United States (42%). The number of blogs written by male and female
      authors was fairly similar: 49% and 44%, respectively, while gender was unknown
      for 7%. Blogs were written by both early- and late-onset PD patients. The
      thematic analysis revealed five major themes: diagnosis, symptoms, treatment,
      coping mechanisms, and information. CONCLUSIONS: Thematic analysis of blogs by PD
      patients provided considerable information and insight regarding the experience
      of these patients, which is significant to other patients and their families, as
      well as to medical professionals. Further qualitative studies of larger blog
      samples utilizing data mining techniques are needed to further explore the
      subjective experiences of patients.

PMID- 29185283
TI  - Surgical Treatment of Neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is the most common non-central nervous system (CNS)
      solid malignant tumor in children. The surgical treatment of high-risk
      neuroblastoma presents a challenge, and the benefits of aggressive surgical
      resection have been called into question. OBJECTIVES: To examine our experience
      with surgical resection of neuroblastoma. METHODS: We report on a retrospective
      chart review of our preliminary surgical experience in 25 patients with
      neuroblastoma who underwent surgery performed by a single surgeon at two
      institutions over a 3 year period. Demographic data, including stage of tumor and
      risk stratification, were recorded. Primary outcome was total gross resection.
      Patients were followed for 3 years after surgery. RESULTS: We found that 80% of
      the patients, including those with high-risk neuroblastoma tumors, had total
      gross resection of their tumor with minimal operative morbidity and no mortality;
      88% had greater than 90% resection of their tumor. Overall, 3 year survival was
      84% (21/25). CONCLUSIONS: Resection of neuroblastoma, even large, high-risk,
      bilateral tumors, was possible when performed by surgical teams with considerable
      experience.

PMID- 29185284
TI  - Re-Examining Distal Resection in Colon Cancer.
AB  - BACKGROUND: In colon cancer, data regarding proximal and distal metastasis to
      lymph nodes remains scarce. OBJECTIVES: To evaluate lymph node distribution along
      the longitudinal axis of the colon as related to a tumor to re-examine the common
      practice of 5 cm proximal and 2 cm distal resection margins. METHODS: We studied
      106 patients (53 males and 53 females, mean age 67.9 +/- 10 years) who had
      undergone left hemicolectomy or sigmoidectomy. Colonic cancer specimens were
      divided into five zones proximally and distally to the tumor. For each zone,
      overall lymph node evaluation and ratio was performed. RESULTS: The mean number
      of retrieved lymph nodes per patient was 24.3 +/- 12, with 54.9% of the nodes
      concentrated in zone I, 22.1% in zone II, 9.5% in zone III, 10.3% in zone IV, and
      3% in zone V. While most positive nodes were found in zone I, significant numbers
      were also detected in both directions proximally and distally to the tumor.
      CONCLUSIONS: It seems that longer colonic segments proximally, and especially
      distally, should be considered for resection to significantly reduce the chances
      of finding involved lymph node.

PMID- 29185286
TI  - Lessons Learned from Imaging on Enthesitis in Psoriatic Arthritis.
AB  - BACKGROUND: Enthesitis is a term that refers to inflammation at tendon, ligament,
      or joint capsule insertions. The entheses are increasinlgly considered to be the
      primary site of joint inflammation in the spondyloarthropathies including
      psoriatic arthritis (PsA). Great advances have occurred in the understanding of
      enthesopathy, which has resulted in a better understanding of the
      etiopathogenesis of PsA. Enthesitis is difficult to assess on both clinical
      examination and on imaging because of the overlap in features between mechanical,
      degenerative, and inflammatory pathologies. Ultrasonography frequently detects
      entheseal abnormalities in patients with psoriasis, despite the absence of
      clinical symptoms of arthropathy and the longitudinal value of such lesions for
      PsA prediction remains unknown. The role of magnetic resonance imaging (MRI) in
      the assessment and monitoring of enthesitis is not fully agreed on but it is
      clearly superior for the assessment of spinal polyenthesitis and for diffuse peri
      enthseal osteitis that can occur anywhere in the skeleton. Nuclear medicine,
      including conventional positron-emission tomography (PET) and high-resolution PET
      scan (hrPET), is more of a research tool for enthesitis and can, for example,
      help distinguish between PsA and osteoarthritis. Entheseal abnormalities are
      common in osteoarthritis, which creates diagnostic difficulty from PsA. Entheseal
      changes, especially on imaging, may also occur in rheumatoid arthritis (RA) and
      likely reflect the extension of the inflammatory process from the adjacent
      synovium. The nail is anatomically anchored to the skeleton via a mini-enthesis
      network. An association between ultrasonography determined distal interphalageal
      joint (DIP) extensor tendon enthesopathy and clinical nail disease was found,
      which highlights the pivotal role of the enthesis in this PsA risk factor. This
      review summarizes the relevant insights and implication of imaging for
      enthesitis, primarily in PsA but also in other arthropathies.

PMID- 29185285
TI  - Posterior Reversible Encephalopathy Syndrome (PRES) Associated with Thrombotic
      Thrombocytopenic Purpura in a Systemic Lupus Erythematosus Patient.

PMID- 29185287
TI  - Lessons Learned from Imaging on Rheumatoid Arthritis.
AB  - BACKGROUND: Over the last 15 years ultrasound has gained importance for the
      clinical management of patients with inflammatory rheumatic diseases, especially
      rheumatoid arthritis. This review summarizes the recent developments and
      achievements in the use of ultrasound in RA, as well as the unmet needs.

PMID- 29185288
TI  - Imaging in Axial Spondyloarthritis.
AB  - BACKGROUND: Axial spondyloarthritis (axSpA) covers the stage of non-radiographic
      axial spondyloarthritis (nr-axSpA) and classic ankylosing spondylitis. The
      pathognomonic findings of axSpA are mainly inflammatory and osteoproliferative
      changes in the sacroiliac joints (SIJ) and the spine. Various imaging techniques
      are being used in daily practice for assessment of disease-specific changes, such
      as periarticular bone marrow edema, erosions, sclerosis, fat metaplasia and
      ankylosis in the SIJ or spondylitis, spondylodiscitis, facet joint involvement,
      or syndesmophytes in the spine of patients with axSpA. Conventional radiographs
      are still considered the gold standard for assessment of structural changes,
      while the method of for detection of inflammatory changes is magnetic resonance
      imaging (MRI). A result for an MRI in the SIJ is considered positive for axSpA
      when more than one lesion is present on one MRI slice, If there is one lesion
      only, this should be present on at least two consecutive slices. For the spine,
      inflammatory lesions should preferably be located in the corner of the vertebral
      bodies, while occurrence of spondylitis in three or more vertebral corners is
      considered highly suggestive of axSpA. This review gives a detailed overview
      about the benefits and limitations of all available imaging techniques in
      patients with axSpA, explains the usage of imaging techniques in the context of
      diagnosis and differential diagnosis of the disease, and reports on the potential
      future trends in the area of imaging of the axial skeleton in patients who are
      suspicious for this diagnosis.

PMID- 29185289
TI  - Severe Hypocalcemia Following a Single Denosumab Injection.

PMID- 29185290
TI  - Two Episodes of Takotsubo Cardiomyopathy in a Woman with a Bilateral
      Adrenalectomy.

PMID- 29185291
TI  - Clinical Images: Marked Inflammation in a Patient with Cervical Vertebral SAPHO
      Complicated by Vertebral Body Collapse and Severe Kyphosis.

PMID- 29185293
TI  - Health literacy: a study of internet-based information on advance directives.
AB  - AIM: The aim of this study was to evaluate the quality and value of web-based
      information on advance directives. Internet-based information on advance
      directives was selected because, if it is inaccurate or difficult to understand,
      patients risk making decisions about their care that may not be followed in
      practice. METHOD: Two validated health information evaluation tools, the
      Suitability Assessment of Materials and DISCERN, and a focus group were used to
      assess credibility, user orientation and effectiveness. FINDINGS: Only one of the
      34 internet-based information items on advance directives reviewed fulfilled the
      study criteria and 30% of the sites were classed as unreadable. In terms of
      learning and informing, 79% of the sites were considered unsuitable. CONCLUSION:
      Using health literacy tools to evaluate internet-based health information
      highlights that often it is not at a functional literacy level and neither
      informs nor empowers users to make independent and valid healthcare decisions.

PMID- 29185292
TI  - Long ranging swept-source optical coherence tomography-based angiography
      outperforms its spectral-domain counterpart in imaging human skin
      microcirculations.
AB  - There is an increasing demand for imaging tools in clinical dermatology that can
      perform in vivo wide-field morphological and functional examination from surface
      to deep tissue regions at various skin sites of the human body. The conventional
      spectral-domain optical coherence tomography-based angiography (SD-OCTA) system
      is difficult to meet these requirements due to its fundamental limitations of the
      sensitivity roll-off, imaging range as well as imaging speed. To mitigate these
      issues, we demonstrate a swept-source OCTA (SS-OCTA) system by employing a swept
      source based on a vertical cavity surface-emitting laser. A series of comparisons
      between SS-OCTA and SD-OCTA are conducted. Benefiting from the high system
      sensitivity, long imaging range, and superior roll-off performance, the SS-OCTA
      system is demonstrated with better performance in imaging human skin than the SD
      OCTA system. We show that the SS-OCTA permits remarkable deep visualization of
      both structure and vasculature (up to ~2  mm penetration) with wide field of view
      capability (up to 18*18  mm2), enabling a more comprehensive assessment of the
      morphological features as well as functional blood vessel networks from the
      superficial epidermal to deep dermal layers. It is expected that the advantages
      of the SS-OCTA system will provide a ground for clinical translation, benefiting
      the existing dermatological practice.

PMID- 29185294
TI  - Preparing supervisors to provide safeguarding supervision for healthcare staff.
AB  - This paper outlines why experienced supervisors at a London healthcare provider
      received skills training so they could offer safeguarding supervision to front
      line colleagues with case management responsibilities for vulnerable children and
      young people. It examines how supervisors use the main functions of supervision
      and a cycle of reflection in clinical practice with supervisees. As well as the
      professional issues encountered by supervisors in relation to the benefits, the
      challenges of providing supervision and the action required to make safeguarding
      supervision a part of the organisational culture are also explored.

PMID- 29185295
TI  - Complications and survival of megaprostheses after resection of bone metastases.
AB  - Treatment of bone metastases is often palliative, aiming at pain control and
      stabilization or prevention of pathological fractures. However, a complete
      resection with healing purposes can be performed in selected cases. The aim of
      our work was to evaluate the survival of megaprostheses used for reconstruction
      after bone metastases. Between January 2001 and March 2015, we implanted 169
      Megasystem-C(r) (Waldemar LINK(r) GmbH & Co. KG, Hamburg, Germany) after bone
      metastasis resection. Patients, 95 females and 74 males, were operated at an
      average age of 61 (12-87) years for proximal femoral resection in 135 (79.9%)
      cases, distal femur in 24 (14.2%), proximal tibia in 6 (3.6%), total femur in 3
      (1.8%) and intercalary femur in 1 (0.6%). Mostly, breast cancer metastases
      (30.8%), kidney (17.8%) and lung (14.2%) were treated. At an average follow-up of
      21 (1-150) months, we found a 99.4% overall limb salvage and a 96.1% overall
      survival rate at 1 year, 92.8% at 2 years, and 86.8% at 5 and 10 years. We found
      9 (5.3%) mobilization cases of the proximal femoral implant, 3 needed surgical
      reduction; 2 (1.2%) cases of aseptic loosening of the prosthetic stem; 2 (1.2%)
      periprotetic infection cases, one requiring a 2-stage revision. Few literature
      studies have evaluated the survival of megaprosthetic implant in the treatment of
      bone metastases. Our data show how in this specific context the rate of
      complications is significantly lower than expected in general orthopedic
      orthopedic surgery. The use of modular prostheses is a valid reconstructive
      strategy after bone metastasis resection in selected patients. The rate of short
      term complications is exceptionally low; further studies will have to confirm
      this in the longer term.

PMID- 29185296
TI  - Evaluation of accuracy of bone cuts and implant positioning in total knee
      arthroplasty using patient specific instrumentation.
AB  - In the last years new surgical techniques are developing to improve prosthesis
      positioning, increasing clinical and functional results and reducing
      invasiveness. In this scenario patient-specific instrumentations have been
      introduced in order to enhance surgical accuracy and ease of implantation. The
      purpose of this study was to assess the compliance of the pre-operative planning
      data with bone resections measured intraoperatively and to evaluate prosthesis
      positioning in patients undergoing total knee arthroplasty (TKA) using an MRI
      based pin-guides instrumentation. Thirty consecutive patients (20 women and 10
      men) undergoing 30 total knee replacements (20 right- and 10 left-sided knees)
      were included in this study. The same cemented cruciate ligament sacrificing
      prosthesis (NexGen LPS, Zimmer, Warsaw, Indiana, USA) was implanted in all
      patients by a single surgeon using Patient-Specific Instruments (PSI, Zimmer,
      Warsaw, Indiana, USA). Femoral and tibial bone resections were measured using a
      manual caliper intra-operatively and compared with the corresponding pre
      operative values. Each patient underwent A CT examination following surgery in
      order to investigate individual component positioning. None of the cases was
      converted from PSI technique to conventional TKA and adequate femoral and tibial
      bone cuts were performed without the need for intraoperative adjustments. Two
      outliers were detected among the intra-operative bone cuts measurements. In all
      patients the size of femoral and tibial prosthetic components, hypothesized at
      preoperative planning, was confirmed intra-operatively. Two outliers were
      detected among post-operative CT measurements as for components positioning. PSI
      system can assist in obtaining good component positioning with reduction of
      outliers. Despite the small number of patients, our data demonstrate the validity
      of this patient-specific pin-guides system in TKA and may support repeatable
      improvements in surgical accuracy. Level of evidence: IV.

PMID- 29185297
TI  - Comparison between different cell sources and culture strategies for tendon
      tissue engineering.
AB  - The aim of this study was to evaluate the effect of an in vitro mechanical
      stimulation by the use of a bioreactor on an engineered tendon for 7 and 14 days
      and to analyze the effect of the use of different cell sources: tenocytes, dermal
      fibroblasts or Adipose-Derived Stem Cells (ASCs), isolated from pig tissues.
      Histology showed a re-organization of the neo-tissue derived from the three cell
      populations along the direction of the stimulus. At T7, cells morphology was
      preserved while an increased cellular suffering at T14 was observed for all cell
      populations. Tenocytes exhibited higher survival than other cells. A stable
      immunopositivity for collagen type 1 or 3 at both time points was also observed.
      In conclusion, dermal fibroblasts and ASCs represent an interesting alternative
      and in vitro culture with mechanical stimuli may enhance the maturation of a
      tendon-like tissue.

PMID- 29185299
TI  - Chemotherapy Agents and Dentistry.

PMID- 29185298
TI  - The analysis of different scaffolds and the benefit of fibrin glue for tendon
      tissue engineering at different culture times.
AB  - This study evaluated a tendon substitute model. Tenocytes were isolated from pig
      Achilles tendon, seeded onto scaffolds (Opocrin 2%, Typeone 3% and Symatese 2%)
      and studied by histology, immunofluorescence for collagen type 1 and 3 and
      biochemical analysis to assess cellularity. The permeability of these compounds
      was evaluated in the presence or absence of fibrin glue. Opocrin 2% was the best
      choice for cellular distribution within the scaffolds, which were then cultured
      for T0, T4, T7 and T10 days. Fibrin glue has been strongly supportive for the
      survival of cells with a significant increase in DNA content at T10 (P<0.05).
      Moreover, the synthetic activity of fibrin-free scaffolds was always negative.
      Lastly, a progressive increase in collagen 1 and 3 with fibrin-glue was observed.
      However, static culture is not sufficient to support long-term cellular
      activities and at T10 there is still a lack of organized matrix similar to the
      native tissue.

PMID- 29185300
TI  - Digital Implant Dentistry: Reducing Treatment Time, Cost, and Manual Skill
      Development.

PMID- 29185302
TI  - Resolving Color Variation.

PMID- 29185301
TI  - Anterior Tooth Replacement Made Easy: A Conservative and Predictable Direct
      Technique.

PMID- 29185303
TI  - Future Trends in Implant Dentistry: Digitally Guided Surgery and Prosthetics.

PMID- 29185304
TI  - Conservative Interdisciplinary Dentistry: A Digital Approach to an Analog
      Problem.

PMID- 29185306
TI  - Technology Impacts Today's GP.

PMID- 29185305
TI  - Successfully Restoring Class III Composites: The Challenge of Deep Subgingival
      Margins.

PMID- 29185307
TI  - Direct anterior approach versus posterolateral approach in total hip
      arthroplasty: effects on early post-operative rehabilitation period.
AB  - Main surgical approaches to the hip have been modified during last decades, in an
      effort to reduce invasiveness of the surgical procedure and allow a faster
      rehabilitation. Direct anterior approach is the only approach, which does not
      require muscle detachment, thus theoretically leading to reduced post-operative
      pain and allows earlier recovery. The aim of this study was to report a
      comparison between patients operated with direct anterior approach and postero
      lateral approach in terms of immediate post-operative and in-hospital records.
      Pain, operative time, intra- and post-operative complications, blood loss,
      hospitalization, motor component of the Functional Independence Measure (M-FIM),
      timed up and go (TUG) test were measured between the two groups and compared.
      Direct anterior approach showed better results in M-FIM, TUG, hospitalization and
      blood loss, without any significant difference for intra- and post-operative
      complications between the 2 groups. This study shows that early post-operative
      recovery is influenced by the chosen approach. Direct anterior approach showed
      better outcomes when compared to postero-lateral approach, limited to
      hospitalization, blood loss, and functional scores. Further comparisons are
      needed to evaluate direct anterior approach to maintain advantages over postero
      lateral approach on longer follow-up period.

PMID- 29185308
TI  - The Occlusion Myth.

PMID- 29185309
TI  - The Future of Implant Dentistry.

PMID- 29185311
TI  - System-Based Endodontics: Does Your Gutta-Percha Master Cone Fit?

PMID- 29185312
TI  - A Mechanical Post Dam Technique.

PMID- 29185310
TI  - CBCT Imaging's Insight Into Endodontic Retreatment Success.

PMID- 29185313
TI  - Focus on: Translucent Zirconia.

PMID- 29185314
TI  - Anti-Aging Movement Drives Aesthetic Care.

PMID- 29185315
TI  - The Future of Pediatric Dentistry.

PMID- 29185317
TI  - Restorative Digital Dentistry, Part 1: The Journey to New Paradigms.

PMID- 29185316
TI  - The Shape of Things to Come.

PMID- 29185318
TI  - Creating a More Youthful Appearance: Multidisciplinary Treatment Planning.

PMID- 29185319
TI  - NiTi Rotary Instrumentation: Achieving Its Full Potential.

PMID- 29185320
TI  - Replacement of a Failing Composite Restoration: Pairing a Self-Etch Adhesive and
      Nanocomposite.

PMID- 29185321
TI  - Treatment Planning for Implant Dentistry.

PMID- 29185322
TI  - Enhanced Diagnosis and Treatment Planning for Implants.

PMID- 29185323
TI  - Maxillo-Mandibular Atrophy: Success Through Interdisciplinary Planning.

PMID- 29185324
TI  - Treating Post-Orthodontic White Spots: A Conservative Resin Infiltration
      Technique.

PMID- 29185325
TI  - Anterior Fiber-Reinforced Fixed Partial Dentures Revisited.

PMID- 29185326
TI  - Minimally Invasive Preps for Thin Porcelain Veneers.

PMID- 29185327
TI  - Inferior Alveolar Nerve Block Revisited.

PMID- 29185328
TI  - Management of Peri-implant Diseases.

PMID- 29185329
TI  - Spotlight on Technology.

PMID- 29185331
TI  - Focus On: Social Media.

PMID- 29185330
TI  - The Future Dental Auxillary is Here.

PMID- 29185332
TI  - Let It Grow.

PMID- 29185333
TI  - In Situ Self-Assembly-Generated 3D Hierarchical Co3O4 Micro/Nanomaterial Series:
      Selective Synthesis, Morphological Control, and Energy Applications.
AB  - A simple in situ self-assembly selective synthetic strategy for one-step
      controllable formation of various three-dimensional (3D) hierarchical Co3O4
      micro/nanomaterials with peculiar morphologies, uniform size, and high quality is
      successfully developed. The morphological control and related impact factors are
      investigated and clarified in detail. The results further clarify the
      corresponding mechanisms on the reaction process, product generation, and
      calcining process as well as the formation of specific morphologies. Furthermore,
      the superior catalytic properties of these materials are confirmed by two typical
      Co-based energy applications on the decomposition of an important solid rocket
      propellant, ammonium perchlorate (AP), and dye-sensitized solar cells (DSSCs).
      The addition of Co3O4 materials to AP obviously decreases the decomposition
      temperatures by about 118-140  degrees C and increases the exothermic heat to a
      great extent. As the substituted counter electrodes of DSSCs, the 3D hierarchical
      Co3O4 materials exhibit attractive photovoltaic performances. These findings
      provide a facile and effective way for designing new types of 3D hierarchical
      materials toward high catalytic activity for energy devices.

PMID- 29185334
TI  - Selective Charging Behavior in an Ionic Mixture Electrolyte-Supercapacitor System
      for Higher Energy and Power.
AB  - Ion-ion interactions in supercapacitor (SC) electrolytes are considered to have
      significant influence over the charging process and therefore the overall
      performance of the SC system. Current strategies used to weaken ionic
      interactions can enhance the power of SCs, but consequently, the energy density
      will decrease due to the increased distance between adjacent electrolyte ions at
      the electrode surface. Herein, we report on the simultaneous enhancement of the
      power and energy densities of a SC using an ionic mixture electrolyte with
      different types of ionic interactions. Two types of cations with stronger ionic
      interactions can be packed in a denser arrangement in mesopores to increase the
      capacitance, whereas only cations with weaker ionic interactions are allowed to
      enter micropores without sacrificing the power density. This unique selective
      charging behavior in different confined porous structure was investigated by
      solid-state nuclear magnetic resonance experiments and further confirmed
      theoretically by both density functional theory and molecular dynamics
      simulations. Our results offer a distinct insight into pairing ionic mixture
      electrolytes with materials with confined porous characteristics and further
      propose that it is possible to control the charging process resulting in
      comprehensive enhancements in SC performance.

PMID- 29185335
TI  - On the Control of Chromophore Orientation, Supramolecular Structure, and
      Thermodynamic Stability of an Amphiphilic Pyridyl-Thiazol upon Lateral
      Compression and Spacer Length Variation.
AB  - The supramolecular structure essentially determines the properties of organic
      thin films. Therefore, it is of utmost importance to understand the influence of
      molecular structure modifications on supramolecular structure formation. In this
      article, we demonstrate how to tune molecular orientations of amphiphilic 4
      hydroxy thiazole derivatives by means of the Langmuir-Blodgett (LB) technique and
      how this depends on the length of an alkylic spacer between the thiazole
      chromophore and the polar anchor group. Therefore, we characterize their
      corresponding supramolecular structures, thermodynamic, absorption, and
      fluorescence properties. Particularly, the polarization-dependence of the
      fluorescence is analyzed to deduce molecular orientations and their possible
      changes after annealing, i.e., to characterize the thermodynamic stability of the
      individual solid state phases. Because the investigated thiazoles are
      amphiphilic, the different solid state phases can be formed and be controlled by
      means of the Langmuir-Blodgett (LB) technique. This technique also allows to
      deduce atomistic supramolecular structure motives of the individual solid phases
      and to characterize their thermodynamic stabilities. Utilizing the LB technique,
      we demonstrate that subtle molecular changes, like the variation in spacer
      length, can yield entirely different solid state phases with distinct
      supramolecular structures and properties.

PMID- 29185336
TI  - Fluoropolymer-Based Flexible Neural Prosthetic Electrodes for Reliable Neural
      Interfacing.
AB  - We covalently bound fluoropolymer (FP) films by plasma treatment followed by
      thermal pressing at temperatures below their melting point and fabricated an
      adhesion-metal-free flexible gold electrode array entirely encapsulated by the FP
      film, excepting the active electrode openings. The fabricated device was
      chemically resistant and was modified to have a lower impedance and efficient
      charge injection capability. The fabricated device was evaluated in vivo in rats
      and was confirmed to record the epidural epileptiform activity induced by
      chemical administration. The chemically inert nature of FPs and the gold
      electrode is expected to facilitate reliable neural interfacing without abiotic
      issues. Plasma treatment-induced covalent binding of FP films can also be
      utilized in a variety of applications requiring durability, such as implantable
      biosensors and sensor platforms operating under chemically harsh environments,
      including humid conditions.

PMID- 29185337
TI  - Gold Nanorods Stabilized by Biocompatible and Multifunctional Zwitterionic
      Copolymer for Synergistic Cancer Therapy.
AB  - A zwitterionic copolymer between methacryloyloxyethyl phosphorylcholine (MPC) and
      methacrylic acid (MA), PMAMPC is introduced as a potential versatile polymeric
      stabilizer for gold nanorods (AuNRs). The MA units in the copolymer serve as
      built-in feature for multiple functionalization, namely introducing additional
      thiol groups as active sites for binding with the AuNRs and conjugating with
      doxorubicin (DOX), an anticancer drug via acid-labile hydrazone linkage. The MPC
      units, on the other hand, provide biocompatibility and antifouling
      characteristics. The chemically modified PMAMPC can act as an effective
      stabilizer for AuNRs yielding PMAMPC-DOX-AuNRs with a fairly uniform size and
      shape with good colloidal stability. In vitro cytotoxicity suggested that PMAMPC
      can not only improve the AuNRs biocompatibility, but also decrease DOX toxicity
      to a certain extent. The PMAMPC-DOX-AuNRs were efficiently internalized inside
      cancer cells and localized in lysosomes, where DOX was presumably acid-triggered
      released as monitored by confocal laser scanning microscopic analysis and flow
      cytometry. Furthermore, the combined photothermal-chemo treatment of cancer cells
      using PMAMPC-DOX-AuNRs exhibited a higher therapeutic efficacy than either single
      treatment alone. These results suggested that the PMAMPC-DOX-AuNRs could
      potentially be applied in pH-triggered drug delivery for synergistic cancer
      therapy.

PMID- 29185338
TI  - Universal Multifunctional Nanoplatform Based on Target-Induced in Situ Promoting
      Au Seeds Growth to Quench Fluorescence of Upconversion Nanoparticles.
AB  - Construction of a new multifunctional chemo/biosensing platform for small
      biomolecules and tumor markers is of great importance in analytical chemistry.
      Herein, a novel universal multifunctional nanoplatform for biomolecules and
      enzyme activity detection was proposed based on fluorescence resonance energy
      transfer (FRET) between upconversion nanoparticles (UCNPs) and target-inducing
      enlarged gold nanoparticles (AuNPs). The reductive molecule such as H2O2 can act
      as the reductant to reduce HAuCl4, which will make the Au seeds grow. The
      enlarged AuNPs can effectively quench the fluorescence of UCNPs owing to the good
      spectral overlap between the absorption band of the AuNPs and the emission band
      of the UCNPs. Utilizing the FRET between the UCNPs and enlarged AuNPs, good
      linear relationship between the fluorescence of UCNPs and the concentration of
      H2O2 can be found. Based on this strategy, H2O2 related molecules such as l
      lactate, glucose, and uric acid can also be quantified. On the basis of UCNPs and
      PVP/HAuCl4, a general strategy for other reductants such as ascorbic acid (AA),
      dopamine (DA), or enzyme activity can be established. Therefore, the universal
      multifunctional nanoplatform based on UCNPs and the target-inducing in situ
      enlarged Au NPs will show its potential as a simple method for the detection of
      some life related reductive molecules, enzyme substrates, as well as enzyme
      activity.

PMID- 29185339
TI  - Ultrabright Fluorescent Silica Nanoparticles Embedded with Conjugated Oligomers
      and Their Application in Latent Fingerprint Detection.
AB  - Fluorescent micro- and nanosized particles have a broad range of applications in
      biology, medicine, and engineering. For these uses, the materials should have
      high emission efficiency and good photostability. However, many organic
      fluorophores suffer from aggregation-induced quenching effects and
      photobleaching. Here, we used a simple method based on covalently blending a
      fluorescent conjugated oligomer with silica nanoparticles to achieve emission
      quantum yields as high as 97%. The resulting system also showed excellent
      stability under continuous light illumination, in a range of pH values and
      temperatures, and in common solvents. This fluorescent material showed
      outstanding properties, including highly efficient blue emission, low cost, low
      toxicity, and easy synthesis. Furthermore, its effectiveness for latent
      fingerprint detection was demonstrated as a proof of concept on various
      substrates. The obtained emissive fingerprint powder gave good
      optical/fluorescent images with high contrast and resolution between the ridges
      and spaces.

PMID- 29185340
TI  - Effect of Fermentation pH on Protein Bioaccessibility of Soymilk Curd with Added
      Tea Polyphenols As Assessed by in Vitro Gastrointestinal Digestion.
AB  - The aim of this study was to compare the effect of fermentation pH on protein
      bioaccessibility of four soymilk curds enriched with tea polyphenols (TP). The
      curds were generated by fermentation with Weissella hellenica D1501 and the
      fermentation terminated at different pH values, namely at pH 5.7, 5.4, 5.1, and
      4.8 (SMTP-5.7, SMTP-5.4, SMTP-5.1, SMTP-4.8). Particle-size distribution, soluble
      protein content, gel electrophoresis, and peptides content were monitored at
      oral, gastric, and intestinal levels. Results showed that SMTP-4.8 was the matrix
      most resistant to protein digestion in the gastric phase according to the soluble
      protein content. Similar particle size distribution and protein degradation
      patterns were observed for these curds in gastric and intestinal phase. However,
      there was a significant difference (P < 0.05) in the content of small peptides
      (<10 kDa) at the end of intestinal digestion among the four curds. Overall,
      terminating fermentation at pH 5.4-5.7 of soymilk curds enriched with TP is
      recommended.

PMID- 29185341
TI  - High-Performance Field Emission from a Carbonized Cork.
AB  - To broaden the range of application of electron beams, low-power field emitters
      are needed that are miniature and light. Here, we introduce carbonized cork as a
      material for field emitters. The light natural cork becomes a graphitic honeycomb
      upon carbonization, with the honeycomb cell walls 100-200 nm thick and the aspect
      ratio larger than 100, providing an ideal structure for the field electron
      emission. Compared to nanocarbon field emitters, the cork emitter produces a high
      current density and long-term stability with a low turn-on field. The nature of
      the cork material makes it quite simple to fabricate the emitter. Furthermore,
      any desired shape of the emitter tailored for the final application can easily be
      prepared for point, line, or planar emission.

PMID- 29185342
TI  - Comparative Proteomics of Enterotoxigenic Escherichia coli Reveals Differences in
      Surface Protein Production and Similarities in Metabolism.
AB  - Enterotoxigenic Escherichia coli (ETEC) infections are an important cause of
      diarrhea among young children living in low- and middle-income countries and
      visiting travelers. The development of effective vaccines is complicated by
      substantial genomic diversity that exists among ETEC isolates. To investigate how
      ETEC genomic variation is reflected at expressed proteome level, we applied label
      free quantitative proteomics to seven human ETEC strains representing five
      epidemiologically important lineages. We further determined the proteome profile
      of the nonpathogenic E. coli B strain BL21(DE3) to discriminate features specific
      for ETEC. The analysis yielded a data set of 2893 proteins, of which 1729 were
      present in all strains. Each ETEC strain produced on average 27 plasmid- or
      chromosomally-encoded proteins with known or putative connections to virulence,
      and a number of strain-specific proteins associated with the biosynthesis of
      surface antigens. Statistical comparison of protein levels between the ETEC
      strains and BL21(DE3) revealed several proteins with considerably increased
      levels only in BL21(DE3) including enzymes of arginine biosynthesis and
      metabolism of melibiose, galactitol, and gluconate. ETEC strains displayed
      consistently increased levels of proteins that were functional in iron
      acquisition, maltose metabolism, and acid resistance. The latter results suggest
      that specific metabolic functions might be shared among ETEC isolates.

PMID- 29185343
TI  - Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial
      Biogenesis by Activating the SIRT1/PGC-1alpha Signaling Pathway.
AB  - Pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in various foods
      and mammalian tissues, has received an increasing amount of attention because of
      a number of health benefits that can be attributed to its ability to enhance
      mitochondrial biogenesis. However, its underlying molecular mechanism remains
      incompletely understood. We have now established that the exposure of mouse
      NIH/3T3 fibroblasts to a physiologically relevant concentration of PQQ
      significantly stimulates mitochondrial biogenesis. The exposure of NIH/3T3 cells
      to 10-100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining,
      mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase
      subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces
      deacetylation of the peroxisome proliferator-activated receptor-gamma-coactivator
      1alpha (PGC-1alpha) and facilitates its nuclear translocation and target gene
      expression but does not affect its protein levels, implying increased activity of
      the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). Indeed, treatment with
      a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC
      1alpha-mediated mitochondrial biogenesis. We also found that the PQQ treatment
      caused a concentration-dependent increase in the cellular NAD+ levels, but not
      the total NAD+ and NADH levels. Our results suggest that PQQ-inducible
      mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1alpha
      signaling pathway by enhancing cellular NAD+ formation.

PMID- 29185344
TI  - Highly Efficient Deep-UV Light-Emitting Diodes Using AlN-Based Deep-UV
      Transparent Glass Electrodes.
AB  - Many studies have set out to develop electrodes that are both highly conductive
      and transparent across a wide spectral region, from visible to deep UV (DUV).
      However, few solutions have been proposed because these two properties are
      mutually exclusive. In this paper, an AlN-based glass electrode film with a
      conducting filament formed by the application of an ac pulse is proposed as a
      solution, which exhibits a high transmittance in the DUV region (over 95.6% at
      280 nm) and a low contact resistance with a p-Al0.4Ga0.6N layer (rhoc = 3.2 * 10
      2 Omega.cm2). The Ohmic conduction mechanism at the interface between the AlN
      film and the p-Al0.4Ga0.6N layers is fully examined using various analytical
      tools. This AlN film is finally applied to a 280 nm top-emitting light-emitting
      diode, to verify the validity of the method, which exhibits very stable
      operations with a forward voltage of 7.7 V at 20 mA, a light output power of 7.49
      mW at 100 mA, and, most importantly, a record high external quantum efficiency of
      2.8% after packaging.

PMID- 29185345
TI  - Evaluating LINE-1 methylation in cleft lip tissues and its association with early
      pregnancy exposures.
AB  - AIM: To pilot investigation of methylation of long interspersed nucleotide
      element-1 in lip tissues from infants with nonsyndromic cleft lip, and its
      association with maternal periconceptional exposures. METHODS: The lateral and
      medial sides of the cleft lips of 23 affected infants were analyzed for long
      interspersed nucleotide element-1 methylation by bisulfite conversion and
      pyrosequencing. RESULTS: The medial side showed 1.8% higher methylation compared
      with the lateral side; p = 0.031, particularly in male infants (2.7% difference;
      p = 0.011) or when the mothers did not take folic acid during periconceptional
      period (2.4% difference; p = 0.011). These results were not statistically
      significant when Bonferroni adjustment was used. CONCLUSION: The observed
      differences in DNA methylation, although nonsignificant after correction for
      multiple comparisons, suggest that differential regulation of the two sides may
      impact lip fusion and warrant larger-scale replication.

PMID- 29185346
TI  - Novel Sigma-1 receptor antagonists: from opioids to small molecules: what is new?
AB  - Sigma-1 (sigma1) receptor has been identified as a chaperone protein that
      interacts with other proteins, such as N-methyl-D-aspartate (NMDA) and opioid
      receptors, modulating their activity. sigma1 receptor antagonists have been
      developed to obtain useful compounds for the treatment of psychoses, pain, drug
      abuse and cancer. Some interesting compounds such as E-5842 (5) and MS-377 (24),
      haloperidol and piperazine derivatives, respectively, were endowed with high
      affinity for sigma1 receptors (Ki sigma1 = 4 and 73 nM; Ki sigma2 = 220 and 6900,
      respectively). They were developed for the treatment of psychotic disorders and 5
      also underwent Phase II clinical trials suggesting interesting potential
      therapeutic applications. Here, sigma1 receptor antagonists have been grouped
      based on chemical structure and reviewed according to structure-activity
      relationship and potential therapeutic role.

PMID- 29185348
TI  - A new chromone and a new aliphatic ester isolated from Daldinia eschscholtzii.
AB  - A new chromone and a new aliphatic ester were isolated from the EtOAc extract of
      myceliums of Daldinia eschscholtzii. Their structures were elucidated as (R)-5
      hydroxy-8-methoxy-2-methylchroman-4-one (1) and (E)-6-(non-3-en-1-yl) -2H-pyran-2
      one (2) by interpretation of the spectroscopic evidence.

PMID- 29185347
TI  - Hyperglycaemia and the SOAR stroke score in predicting mortality.
AB  - BACKGROUND: We assessed the association between admission blood glucose levels
      and acute stroke mortality and examined whether there was any incremental value
      of adding glucose status to the validated acute stroke mortality predictor - the
      SOAR (stroke subtype, Oxford Community Stroke Project classification, age, and
      pre-stroke modified Rankin) score. METHODS: Data from Norfolk and Norwich
      University Hospital stroke and Transient Ischaemic Attack register (2003-2013)
      and Anglia Stroke Clinical Network Evaluation Study (2009-2012) were analysed.
      Multivariable logistic regression analysis assessed the association between
      admission blood glucose levels with inpatient and 7-day mortality. The prognostic
      ability of the SOAR score was then compared with the SOAR with glucose score.
      RESULTS: A total of 5575 acute stroke patients (ischaemic stroke: 89.2%) with
      mean age (standard deviation) of 76.97 ( +/- 11.88 ) years were included. Both
      borderline hyperglycaemia (7.9-11.0 mmol/L) and hyperglycaemia (>11.0 mmol/L)
      when compared to normoglycaemia (4.0-7.8 mmol/L) were associated with both 7-day
      and inpatient mortality after controlling for sex, age, Oxford Community Stroke
      Project classification and pre-stroke modified Rankin score. Both the SOAR stroke
      score and SOAR-G score were good predictors of inpatient stroke mortality [area
      under the curve: 0.82 (95% confidence interval: 0.81-0.84) and 0.83 (95%
      confidence interval: 0.81-0.84)], respectively. These scores were also good at
      predicting outcomes in both patients with and without diabetes. CONCLUSION: High
      blood glucose levels at admission were associated with worse acute stroke
      mortality outcomes. The constituents of the SOAR stroke score were good at
      predicting mortality after stroke.

PMID- 29185349
TI  - Adipose tissue macrophage polarization in cardiovascular disease.

PMID- 29185350
TI  - Arthroscopic Resection of Dorsal Wrist Ganglion: Results and Rate of Recurrence
      Over a Minimum Follow-up of 4 Years.
AB  - BACKGROUND: Dorsal wrist ganglia are the most common soft tissue tumor type of
      the upper limb. Surgical resection, open or arthroscopic, is one of the most
      frequent procedures performed by hand surgeons. This study sought to perform an
      objective evaluation of the outcomes of arthroscopic resection of dorsal wrist
      ganglia and their recurrence rates over 4 years. Patients treated with
      arthroscopic resection were expected to have favorable outcomes and low
      complication rates after 4 years of follow-up. METHODS: We evaluated 34 cases of
      dorsal wrist ganglia in patients who underwent arthroscopic resection. The
      patients were evaluated using the Quick-Disabilities of the Arm, Shoulder and
      Hand (QuickDASH) outcome measure, visual analog scale (VAS) for pain, range of
      motion of the wrist, palmar grip strength, rates of recurrence, and
      complications. RESULTS: During the postoperative period, the QuickDASH score
      averaged 2.3 points, the mean residual pain by VAS was 0.54, full range of wrist
      movement was recovered by all patients, and the mean palmar grip strength was
      29.4 kgf; there was 1 case with recurrence. There were no severe postoperative
      complications throughout the follow-up period. CONCLUSIONS: The outcomes,
      recurrence, and complications rates after 4 years of follow-up presented in this
      study support the use of arthroscopy as a treatment for dorsal wrist ganglion.

PMID- 29185351
TI  - Irreducible Galeazzi Fracture-Dislocations.
AB  - BACKGROUND: Fractures of the radial shaft with disruption of the distal radial
      ulnar joint (DRUJ) or Galeazzi fractures are treated with reduction of the radius
      followed by stability assessment of the DRUJ. In rare instances, the reduction of
      the DRUJ is blocked by interposed structures requiring open reduction of this
      joint. The purpose of this study is to review all cases of irreducible Galeazzi
      fracture-dislocations reported in the literature to offer guidelines in the
      diagnosis and management of this rare injury. METHODS: A search of the MEDLINE
      database, OVID database, and PubMed database was employed using the terms
      "Galeazzi" and "fracture." Of the 124 articles the search produced, a total of 12
      articles and 17 cases of irreducible Galeazzi fracture-dislocations were found.
      RESULTS: The age range was 16 to 64 years (mean = 25 years). A high-energy
      mechanism of injury was the root cause in all cases. More than half of the
      irreducible DRUJ dislocations were not identified intraoperatively. In a dorsally
      dislocated DRUJ, a block to reduction in most cases (92.3%) was secondary to
      entrapment of one or more extensor tendons including the extensor carpi ulnaris,
      extensor digiti minimi, and extensor digitorum communis, with the remaining cases
      blocked by fracture fragments. Irreducible volar dislocations due to entrapment
      of the ulnar head occurred in 17.6% of cases with no tendon entrapment noted.
      CONCLUSIONS: In the presence of a Galeazzi fracture, a reduced/stable DRUJ needs
      to be critically assessed as more than half of irreducible DRUJs in a Galeazzi
      fracture-dislocation were missed either pre- or intraoperatively.

PMID- 29185352
TI  - Psychological distress and unmet mental health needs among urban taxi drivers: A
      cross-sectional survey.
AB  - OBJECTIVES: The taxi industry relies on a male-dominated, predominately immigrant
      workforce who face multiple risk factors for poor mental health including shift
      work, low pay and threats of violence. Despite these risk factors, no previous
      study has documented the prevalence of psychological distress in the taxi
      industry. We investigated psychological distress among urban taxi drivers and
      explored the factors associated with high levels of distress. METHOD: A total of
      380 taxi drivers were surveyed at the Melbourne Airport holding yard between
      September 2016 and March 2017. Psychological distress was measured using the K10.
      Logistic regression models were used to estimate the association between high
      levels of psychological distress and migration, work patterns, potentially
      traumatic events, health care use and social connectedness. RESULTS: A third
      (33%) of drivers had very high (K10 ? 30) levels of distress and 28% had high
      (K10 = 22-29) levels of distress. Trauma was significantly associated with high
      levels of psychological distress, and rates of trauma were much higher among
      drivers than among the Australian population. Despite high levels of distress,
      drivers were no more likely than other Australian men to visit a health
      professional. CONCLUSION: Urban taxi drivers are at very high risk for mental
      health problems, yet the mental health needs of this largely immigrant workforce
      has gone largely unnoticed. Interventions tailored to the unique characteristics
      of the job and the demographic composition of the workforce are urgently needed.

PMID- 29185353
TI  - Facile synthesis of some pyrazoline-based compounds with promising anti
      inflammatory activity.
AB  - AIM: Search for new anti-inflammatory agents with higher efficacy and lower
      toxicity is an urgent demand in drug discovery era. METHODOLOGY: Different
      pyrazoline derivatives 4a,b, 5a,b, 6a-h and 7a-f were prepared from the
      condensation reactions of 1,5-bis(5-methylfuran/thiophen-2-yl)penta-1,4-dien-3
      ones 3a,b with different hydrazine derivatives. All compounds were screened for
      their anti-inflammatory activity using the carrageenan-induced paw edema method
      in rats and TNF-alpha inhibition assay. RESULTS: Many compounds revealed
      promising anti-inflammatory activity relative to indomethacin especially
      compounds 4a, 5a, 5b, 6b, 6d, 6f and 7b. They were safe to the gastric mucosa and
      did not cause toxicity up to tenfolds the anti-inflammatory dose, in addition,
      all compounds inhibited TNF-alpha with IC50 values of 1.7-100 nM.

PMID- 29185354
TI  - Validation and Psychometric Properties of the German Version of the Delirium
      Motor Subtype Scale (DMSS).
AB  - OBJECTIVE: Delirium has been characterized into its subtypes-hypoactive,
      hyperactive, mixed, or no motor subtype-along with the use of the Delirium Motor
      Symptom Scale (DMSS). The German version of this scale (DMSS-G), however, has not
      yet been validated. METHOD: We determined internal consistency, reliability, and
      validity of the DMSS-G in the surgical intensive care unit, using DSM-IV-TR
      criteria and the Delirium Rating Scale-Revised-98. RESULTS: In total, 289
      patients were included, and out of these, 122 were delirious. The DMSS-G showed
      excellent internal consistency (Cronbach's alpha = 0.92) and interrater
      reliability (Fleiss kappa = 0.83). Additionally, the overall concurrent validity
      was substantial (Cramer's V = 0.69); within subtypes, hyperactive, hypoactive, or
      mixed, the concurrent validity remained at least substantial (Cohen's kappa =
      0.73-0.82) and the sensitivity ranged from 60% to 97%. In contrast, in those with
      no motor subtype, we found the concurrent validity (Cohen's kappa = 0.31) and
      sensitivity to be low (22%). Overall, specificity for all individual subtypes was
      high (82% to 100%). The DMSS was very sensitive in both rating hyperactive and
      hypoactive motor symptoms of delirium. CONCLUSION: The DMSS-G is a highly
      reliable and valid instrument for detecting motor symptoms in delirium, which
      provides an accurate instrument to classify the motor subtypes of delirium.

PMID- 29185355
TI  - The Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Rat's
      Subglottic Stenosis Model.
AB  - OBJECTIVE: Subglottic stenosis remains a clinical challenge. The aim of this
      study was to evaluate the effect of human adipose tissue-derived mesenchymal stem
      cells (hAMSCs) in rat model of subglottic stenosis. SUBJECTS AND METHODS: Ninety
      six 13-week-old male rats were enrolled in this study. They were divided into 3
      groups as normal control (NC) group, a subglottic injury and media injection (SM)
      group, and a subglottic injury and media-stem cell injection (SMSC) group. The
      hAMSCs were immediately injected into subglottis after injury. Histologic
      characteristics of subglottis; the mRNA expressions of interleukin-1beta,
      cyclooxygenase-2, tumor growth factor-beta and basic fibroblast growth factor;
      and hAMSCs' survival were evaluated. RESULTS: The hAMSCs survived in the
      subglottis of the rat until 10 days after implantation. The NC and SMSC groups
      had a significantly wider subglottic lumen and thinner lamina propria than the SM
      group at 56 days after injury. Collagen intensity of subglottis was significantly
      higher in the SM group than in the NC and SMSC groups at 28 days after injury.
      Gene expression didn't show significant difference between the SM group and the
      SMSC group. CONCLUSIONS: The hAMSCs injection was found to be helpful for
      preventing subglottic stenosis in a rat model.

PMID- 29185356
TI  - A profile of social, separation and generalized anxiety disorders in an
      Australian nationally representative sample of children and adolescents:
      Prevalence, comorbidity and correlates.
AB  - OBJECTIVE: To examine (1) the 12-month prevalence of social anxiety disorder
      (SOC), separation anxiety disorder (SEP) and generalized anxiety disorder (GAD)
      in a large, nationally representative sample of Australian youth; (2) patterns of
      comorbidity between these disorders; (3) demographic and socio-environmental
      correlates and (4) the psychosocial impact and service use associated with each
      condition. METHOD: Data are from the 2013/2014 Australian national, face-to-face
      household Young Minds Matter survey of mental health and wellbeing. Informants
      were parents or carers reporting on 6310, 4- to 17-year-olds (55% of eligible
      households). The presence of each of the three anxiety disorders was determined
      based on the Diagnostic Interview Schedule for Children-Version IV. RESULTS: In
      the past 12 months, 6.6% of youth had experienced at least one of SOC, SEP or
      GAD, with rates of 2.3% for SOC, 4.3% for SEP and 2.3% for GAD. Rates did not
      differ by gender but were significantly higher for SOC and GAD and lower for SEP
      in 12- to 17-year-olds than 4- to 11-year-olds. Comorbidity between these
      disorders was high, although lower for SEP. Having SOC, SEP or GAD was associated
      with not living with both biological parents, having a parent with a mental
      health problem, elevated negative family events, low carer employment and peer
      victimization. The association with family risk factors was greater for SEP than
      for SOC and GAD. Although the majority of anxious youth had received professional
      help, this was less likely in the younger cohort. CONCLUSION: Social, separation
      and generalized anxiety disorders in young people are relatively common and
      impairing, with a high level of comorbidity. There are both commonalities and
      differences in socio-environmental correlates. The majority of anxious youth
      received some form of professional assistance, although the rate was lower among
      children compared to adolescents.

PMID- 29185357
TI  - When Old Habits Train a New Generation: Findings From a National Survey of
      Internal Medicine Program Directors on Procedural Training.
AB  - Resident physicians routinely perform bedside procedures that pose substantial
      risk to patients. However, no standard programmatic approach to supervision and
      procedural competency assessment among residents currently exists. The authors
      performed a national survey of internal medicine (IM) program directors to
      examine procedural assessment and supervision practices of IM residency programs.
      Procedures chosen were those commonly performed by medicine residents at the
      bedside. Of the 368 IM programs, 226 (61%) completed the survey. Programs
      reported the predominant method of training as 171 (74%) apprenticeship and 106
      (46%) as module based. The majority of programs used direct observation to attest
      to competence, with 55% to 62% relying on credentialed residents. Most programs
      also relied on a minimum number of procedures to determine competence (64%-88%),
      72% of which reported 5 procedures (a lapsed historical standard). This national
      survey demonstrates that procedural assessment practices for IM residents are
      insufficiently robust and may put patients at undue risk.

PMID- 29185358
TI  - Simplified Summative Temporal Bone Dissection Scale Demonstrates Equivalence to
      Existing Measures.
AB  - INTRODUCTION: Emphasis on patient safety has created the need for quality
      assessment of fundamental surgical skills. Existing temporal bone rating scales
      are laborious, subject to evaluator fatigue, and contain inconsistencies when
      conferring points. To address these deficiencies, a novel binary assessment tool
      was designed and validated against a well-established rating scale. METHODS:
      Residents completed a mastoidectomy with posterior tympanotomy on identical 3D
      printed temporal bone models. Four neurotologists evaluated each specimen using a
      validated scale (Welling) and a newly developed "CanadaWest" scale, with scoring
      repeated after a 4-week interval. RESULTS: Nineteen participants were clustered
      into junior, intermediate, and senior cohorts. An ANOVA found significant
      differences between performance of the junior-intermediate and junior-senior
      cohorts for both Welling and CanadaWest scales ( P < .05). Neither scale found a
      significant difference between intermediate-senior resident performance ( P >
      .05). Cohen's kappa found strong intrarater reliability (0.711) with a high
      degree of interrater reliability of (0.858) for the CanadaWest scale, similar to
      scores on the Welling scale of (0.713) and (0.917), respectively. CONCLUSION: The
      CanadaWest scale was facile and delineated performance by experience level with
      strong intrarater reliability. Comparable to the validated Welling Scale, it
      distinguished junior from senior trainees but was challenged in differentiating
      intermediate and senior trainee performance.

PMID- 29185359
TI  - Gualou Guizhi decoction reverses brain damage with cerebral ischemic stroke,
      multi-component directed multi-target to screen calcium-overload inhibitors using
      combination of molecular docking and protein-protein docking.
AB  - Stroke is a disease of the leading causes of mortality and disability across the
      world, but the benefits of drugs curative effects look less compelling,
      intracellular calcium overload is considered to be a key pathologic factor for
      ischemic stroke. Gualou Guizhi decoction (GLGZD), a classical Chinese medicine
      compound prescription, it has been used to human clinical therapy of sequela of
      cerebral ischemia stroke for 10 years. This work investigated the GLGZD improved
      prescription against intracellular calcium overload could decreased the
      concentration of [Ca2+]i in cortex and striatum neurone of MCAO rats. GLGZD
      contains Trichosanthin and various small molecular that they are the potential
      active ingredients directed against NR2A, NR2B, FKBP12 and Calnodulin target
      proteins/enzyme have been screened by computer simulation. "Multicomponent
      systems" is capable to create pharmacological superposition effects. The Chinese
      medicine compound prescriptions could be considered as promising sources of
      candidates for discovery new agents.

PMID- 29185360
TI  - Role of metformin on base excision repair pathway in p53 wild-type H2009 and
      HepG2 cancer cells.
AB  - The antidiabetic agent metformin was shown to further possess chemopreventive and
      chemotherapeutic effects against cancer. Despite the advances, the underlying
      molecular mechanisms involved in decreasing tumor formation are still unclear.
      The understanding of the participation of oxidative stress in the action
      mechanism of metformin and its related effects on p53 and on DNA base excision
      repair (BER) system can help us to get closer to solve metformin puzzle in
      cancer. We investigated the effects of metformin in HepG2 and H2009 cells,
      verifying cytotoxicity, oxidative stress, antioxidant status, and DNA BER system.
      Our results showed metformin induced oxidative stress and reduced antioxidant
      capacity. Also, metformin treatment with hydrogen peroxide (H2O2) enhanced these
      effects. Although DNA BER enzyme activities were not changed accordantly together
      by metformin as a single agent or in combination with H2O2, activated p53 was
      decreased with increased oxidative stress in H2009 cells. Our study on the
      relationship between metformin/reactive oxygen species and DNA BER system in
      cancer cells would be helpful to understand the anticancer effects of metformin
      through cellular signal transduction pathways. These findings can be a model of
      the changes on oxidative stress that reflects p53's regulatory role on DNA repair
      systems in cancer for the future studies.

PMID- 29185361
TI  - Melatonin concentration in follicular fluid is correlated with antral follicle
      count (AFC) and in vitro fertilization (IVF) outcomes in women undergoing
      assisted reproductive technology (ART) procedures.
AB  - The aim of the present study was to evaluate the possible relationship between
      melatonin levels in the follicular fluid (FF) and in vitro fertilization (IVF)
      outcomes in women undergoing assisted reproductive treatment. Sixty-three females
      (20 to 40 years old) scheduled for IVF were divided into three groups based on
      their antral follicle count (AFC). We determined FF melatonin concentrations in
      group A (AFC?6, n = 21), group B (7?AFC?14, n = 22), group C (AFC?15, n = 20) on
      oocyte retrieval day. Patients in group C had significantly higher melatonin
      levels as compared to patients in groups A and B (p < .001). Melatonin levels of
      the patients were significantly positively correlated with antral follicle count
      (AFC, p < .001), serum anti-Mullerian hormone(AMH) levels (p =.001), serum
      estradiol (E2) levels on human chorionic gonadotropin (HCG) administration day (p
      = .001), total follicle-stimulating hormone (FSH) dose (p = .002), starting FSH
      dose (p = .035), number of retrieved oocytes (p < .001), total fertilized oocytes
      (p < .001), normally fertilized oocytes (p < .001), cleaved oocytes (p < .001),
      number of high-quality day 3 embryos (p = .004), blastocysts obtained (p = .007)
      and total embryos obtained (day3 embryos + day5/6 blastocysts) (p = .005). The
      levels were significantly negatively correlated with age (p < .001), basal serum
      FSH levels (p = .003), serum FSH (p = .001) and serum luteinizing hormone (LH)
      levels (p = .003) on HCG administration day. This is the first demonstration of a
      significant positive correlation of melatonin concentrations with AFC in patients
      undergoing IVF. We propose that FF melatonin levels may influence the IVF
      outcomes.

PMID- 29185362
TI  - Living with incurable cancer: what are the rehabilitation needs in a palliative
      setting?
AB  - BACKGROUND: Increasing numbers of people are living with incurable cancers.
      Symptoms, side effects, and treatment burdens impact on physical functioning, yet
      little is known about the impact on people's lives and how best to provide
      rehabilitation. MATERIALS AND METHODS: A qualitative study employing a
      phenomenological approach explored the lived experience of incurable cancer. A
      purposive sample of six people participated in semi-structured interviews. The
      data were analysed thematically at a semantic level to identify the functional
      difficulties experienced by people living with incurable cancer, the meanings of
      those difficulties, and participants perceived rehabilitation needs. RESULTS:
      People living with incurable cancer described cancer-related issues spanning all
      five domains of the International Classification of Functioning, Disability and
      Health (ICF). Although highly valued amongst study participants, rehabilitation
      services were difficult to access, poorly utilised, and referrals were sporadic
      and consequential; indicative of poor awareness of rehabilitation for people with
      incurable cancer amongst potential referrers. DISCUSSION: Participants valued a
      change in terminology away from "palliative" towards more positive language in
      line with enhanced supportive care movements. Validated tools such as the
      Palliative Care Therapy Outcome Measure, which align with the ICF, would allow
      rehabilitation professionals to demonstrate maintenance or improvement in
      participation and wellbeing. Implications for Rehabilitation Incurable cancer
      leads to a fluctuating multifactorial disability. People living with incurable
      cancer can benefit from rehabilitation input throughout their illness. Offering
      flexible and varied rehabilitation options for people living with incurable
      cancer will increase physical and emotional well-being, function, and coping.
      Allied health professionals should take and create opportunities to promote
      rehabilitation for people living with incurable cancer and their services to
      other potentially referring healthcare professionals to increase understanding of
      benefits and utilisation of available services for people living with incurable
      cancer.

PMID- 29185363
TI  - Do Hispanic Girls Develop Eating Disorders? A Critical Review of the Literature.
AB  - INTRODUCTION: Eating disorders have become increasingly prevalent in North
      America. Anorexia nervosa, bulimia nervosa, and binge eating disorder were
      previously thought to solely affect Caucasian women. However, contemporary
      research has studied the occurrence of this phenomenon in ethnic minority women,
      such as Latinas. METHODS: This article presents a critical review of 12
      quantitative, prospective psychological research studies from the past 17 years.
      RESULTS: The authors in the reviewed literature identified bodily
      dissatisfaction, environmental influences, and acculturation as significant risk
      factors in the development of eating disorders in Hispanic girls and women.
      CONCLUSION: The methodology and empirical findings from these studies are
      discussed, and suggestions for future research and culturally sensitive clinical
      treatment are considered.

PMID- 29185364
TI  - The effect of oxidative stress on the progression of Hashimoto's thyroiditis.
AB  - OBJECTIVE: We aimed to investigate the effects of oxidative stress in the
      pathogenesis and progression of Hashimoto's thyroiditis (HT). METHODS: Forty
      euthyroid and 40 subclinical hypothyroid patients older than 18 years and not yet
      had received treatment were enrolled in the study. RESULTS: In the 9 months
      follow-up, 14 of the HT patients developed overt hypothyroidism. The mean total
      oxidant status (TOS) and oxidative stress index (OSI) were higher in patients who
      developed overt hypothyroidism than those who did not (p < .001). And no
      significant difference was found between the two groups in terms of paraoxanase-1
      and arylesterase (p > .05). Multivariable Cox regression model showed thyroid
      stimulating hormone level (HR = 1.348, p < .001), free-thyroxine level (HR =
      0.481, p = .017) and OSI ratio (HR = 2.349, p < .001) to be independent
      predictors of development of overt hypothyroidism. OSI level, being over 2.96
      with 92.9% sensitivity and 62.5% specificity, predicts the risk of
      hypothyroidism. CONCLUSION: Oxidative stress may be an effective risk factor in
      the development of overt hypothyroidism in HT.

PMID- 29185365
TI  - Synthesis and antitumor activity of novel 2, 3-didithiocarbamate substituted
      naphthoquinones as inhibitors of pyruvate kinase M2 isoform.
AB  - The M2 isoform of pyruvate kinase (PKM2) is a potential antitumor therapeutic
      target. In this study, we designed and synthesised a series of 2, 3
      didithiocarbamate substituted naphthoquinones as PKM2 inhibitors based on the
      lead compound 3k that we previously reported. Among them, compound 3f (IC50 =
      1.05 +/- 0.17 uM) and 3h (IC50 = 0.96 +/- 0.18 uM) exhibited potent inhibition of
      PKM2, and their inhibitory activities are superior to compound 3k (IC50 = 2.95 +/
      0.53 uM) and the known PKM2 inhibitor shikonin (IC50 = 8.82 +/- 2.62 uM). In
      addition, we evaluated in vitro antiproliferative effects of target compounds
      using MTS assay. Most target compounds exhibited dose-dependent cytotoxicity with
      IC50 values in nanomolar concentrations against HCT116, MCF7, Hela, H1299 and B16
      cells. These small molecule PKM2 inhibitors not only provide candidate compounds
      for cancer therapy, but also offer a tool to probe the biological effects of PKM2
      inhibition on cancer cells.

PMID- 29185366
TI  - The Dutch version of the self-report Child Activity and Limitations Interview in
      adolescents with chronic pain.
AB  - PURPOSE: To assess the factor structure, related constructs and internal
      consistency of the Child Activity Limitation Interview 21-Child version for use
      in Dutch-language countries. METHODS: Cross-sectional validation study: After
      forward and back translation of the Dutch version of the Child Activity
      Limitation Interview 21-Child adolescents (11-21 years old) with chronic
      musculoskeletal pain completed an assessment. The assessment contained the Dutch
      Child Activity Limitation Interview, and questionnaires about demographics, pain
      intensity, functional disability, anxiety and depression. Internal consistency
      and construct validity were evaluated through exploratory factor analysis
      (principal axis factoring with oblique rotation) and hypotheses testing using
      pain intensity, activity limitations, anxiety and depression as comparative
      constructs. RESULTS: Seventy-four adolescents completed the assessment.
      Exploratory factor analysis resulted in a two-factor structure, explaining 50% of
      the variance. Internal consistency was good (Cronbach's alpha = 0.91 total scale,
      alpha = 0.90 Factor 1, alpha = 0.80 Factor 2). All nine hypotheses were
      confirmed. CONCLUSION: The Dutch version can be used to assess pain-related
      disability in Dutch-speaking adolescents comparable to the study sample. Scores
      on both subscales provide insight into the severity of the pain-related
      disability in both daily routine and more physically vigorous activities.
      Implications for Rehabilitation Chronic pain is a disabling disorder which not
      only impacts physically but restricts quality of life. This study provides
      clinicians a questionnaire to measure pain-related disability and quantify the
      impact of pain on the daily living of adolescents. The advantage of the Dutch
      version of the Child Activity and Limitations Interview over other measurements
      is that it can distinguish limitations in daily activities from more physically
      vigorous activities.

PMID- 29185367
TI  - Aiming to Deceive: Examining the Role of the Quiet Eye During Deceptive Aiming
      Actions.
AB  - In three experiments, we explored the use of deceptive gaze in soccer penalty
      takers using eye-tracking equipment. In Experiment 1, players competed against a
      goalkeeper while taking unconstrained shots. Results indicated that when players
      used deception (looking to the opposite side to which they shot), they extended
      the duration of their final aiming (quiet eye) fixation and maintained shooting
      accuracy. In Experiment 2, with no goalkeeper present, players still used
      extended quiet-eye durations when using a deceptive strategy, but this time,
      their accuracy suffered. In Experiment 3, we manipulated the goalkeeper's
      location while controlling for the use of peripheral vision and memory of goal
      size. Results indicated that increased quiet-eye durations were required when
      using deceptive aiming, and that accuracy was influenced by the position of the
      goalkeeper. We conclude that during deceptive aiming, soccer players maintain
      accuracy by covertly processing information related to the goalkeeper's location.

PMID- 29185368
TI  - The Digest.

PMID- 29185369
TI  - Cellular effects of thirdhand tobacco smoke from smokers' homes.
AB  - After the cigarette is extinguished, many toxic compounds remain in the
      environment and accumulate in the air or on surfaces. This exposure is termed
      thirdhand smoke (THS) and its risks are poorly known. The aim of the study was to
      evaluate the cellular effects of THS from smokers' homes. Papers were placed in
      nine smoker's home and three nonsmoker's homes. An area equivalent to the paper
      size was cleaned with a cotton wipe. A549, Hep-2 and 3T3 cells were exposed to
      THS for 24 h and cellular functions were assessed by MTT, neutral red (NR)
      reuptake and trypan blue exclusion assays. High levels of nicotine were found in
      samples from smokers' homes. Cellular proliferation was similar in almost all
      samples after THS exposure. Few changes in the cellular functions were observed,
      mainly higher mitochondrial activity, in paper samples. We are able to detect
      markers of THS collected from smokers' homes, but a clear evidence of cellular
      toxicity cannot be demonstrated by the present assays. This is the first study to
      evaluate the cellular effects of THS samples collected from smokers' homes.

PMID- 29185370
TI  - Effect of nicotine on placental ischemia-induced complement activation and
      hypertension in the rat.
AB  - Preeclampsia is a pregnancy-specific condition manifested by new-onset maternal
      hypertension with systemic inflammation, including increased innate immune system
      complement activation. While exact pathophysiology is unknown, evidence suggests
      that inadequate spiral artery invasion and resulting utero-placental
      insufficiency is the initiating event. Cigarette smoking during pregnancy
      decreases the risk of preeclampsia. Nicotine, a major component of cigarettes,
      stimulates the efferent cholinergic anti-inflammatory pathway through
      peripherally expressed nicotinic acetylcholine receptors (nAChR) and is known to
      attenuate ischemia-reperfusion injury in kidney and liver. Prior studies
      indicated that complement activation was critical for placental ischemia-induced
      hypertension in a rat model. Thus, it was hypothesized here that nicotine was
      responsible for the protective effect of cigarette smoking in preeclampsia and
      would attenuate placental ischemia-induced systemic complement activation and
      hypertension. The Reduced Utero-placental Perfusion Pressure (RUPP) model in the
      pregnant rat was employed to induce placental ischemia, resulting in complement
      activation, fetal resorptions, and hypertension. On gestation day (GD)14,
      nicotine (1 mg/kg) or saline was administered via subcutaneous injection prior to
      RUPP surgery and daily through GD18. On GD19, placental ischemia significantly
      increased mean arterial pressure (MAP) in saline injected animals. However, the
      placental ischemia-induced increase in blood pressure was not evident in nicotine
      treated animals and nicotine treatment significantly increased MAP variability.
      Circulating C3a was measured as an indicator of complement activation and
      increased C3a in RUPP compared to Sham persisted with nicotine treatment, as did
      fetal resorptions. These data suggested to us that nicotine may contribute to the
      decreased risk of preeclampsia with cigarette smoking, but this protective effect
      was confounded by additional effects of nicotine on the cardiovascular system.

PMID- 29185371
TI  - Recent advances in longitudinal structural neuroimaging of younger-onset
      dementias.

PMID- 29185372
TI  - Recent advances in the microbiological diagnosis of bloodstream infections.
AB  - Rapid identification (ID) and antimicrobial susceptibility testing (AST) of the
      causative agent(s) of bloodstream infections (BSIs) are essential for the prompt
      administration of an effective antimicrobial therapy, which can result in
      clinical and financial benefits. Immediately after blood sampling, empirical
      antimicrobial therapy, chosen on clinical and epidemiological data, is
      administered. When ID and AST results are available, the clinician decides
      whether to continue or streamline the antimicrobial therapy, based on the results
      of the in vitro antimicrobial susceptibility profile of the pathogen. The aim of
      the present study is to review and discuss the experimental data, advantages, and
      drawbacks of recently developed technological advances of culture-based and
      molecular methods for the diagnosis of BSI (including mass spectrometry, magnetic
      resonance, PCR-based methods, direct inoculation methods, and peptide nucleic
      acid fluorescence in situ hybridization), the understanding of which could
      provide new perspectives to improve and fasten the diagnosis and treatment of
      septic patients. Although blood culture remains the gold standard to diagnose
      BSIs, newly developed methods can significantly shorten the turnaround time of
      reliable microbial ID and AST, thus substantially improving the diagnostic yield.

PMID- 29185374
TI  - THE DIGEST.

PMID- 29185373
TI  - THE DIGEST.

PMID- 29185375
TI  - The Effects of Family-Based Mindfulness Intervention on ADHD Symptomology in
      Young Children and Their Parents: A Randomized Control Trial.
AB  - OBJECTIVE: The aim of the study is to investigate the feasibility of a family
      based mindfulness intervention in improving children with inattention and
      hyperactivity symptoms. METHOD: A total of 100 children aged 5 to 7 years with
      ADHD symptoms and their parents were randomly assigned to a family-based
      mindfulness intervention ( n = 50) or a wait-list control group ( n = 50).
      RESULTS: Families from intervention group had greater improvements in children's
      ADHD symptoms, with medium effect sizes of -0.60 for inattention and -0.59 for
      hyperactivity; overall behaviors; and parenting stress and well-being than those
      in wait-list control group. CONCLUSION: The positive results on the child primary
      outcome measures have provided initial evidence of the family-based mindfulness
      intervention as a treatment option to ADHD. The reduction of parental stress and
      increase in psychological well-being has demonstrated the value of mindfulness in
      enhancing parent's self-management.

PMID- 29185376
TI  - Effect of the additional first ray osteotomy on hindfoot alignment after
      calcaneal osteotomy for the correction of mild-to-moderate adult type pes plano
      valgus.
AB  - PURPOSE: To determine the effect of the additional first ray osteotomy on
      hindfoot alignment for the correction of pes plano-valgus. METHODS: Data obtained
      from 37 consecutive patients recruited from 2006 to 2014 who underwent medial
      displacement calcaneal osteotomy (MDCO) alone (group H) or MDCO followed by
      medial cuneiform opening wedge osteotomy (MCOWO) (group HF) with a minimum 1-year
      follow-up were reviewed retrospectively. The mean follow-up periods were 34 and
      32 months. RESULTS: Degree of decrease of Talonavicular coverage angle (TNCA) via
      surgery or postoperative TNCA on standing foot AP radiographs were not
      significantly different between group H and HF ( p = 0.287). The calcaneal pitch
      angle and medial cuneiform height on the standing foot lateral radiographs was
      significantly increased after operation in group HF ( p = 0.01), there was a
      significant difference with group H as well ( p = 0.033). In group HF, the
      Meary's angle was significantly decreased after operation, a significant
      difference compared to group H ( p = 0.009). Hindfoot alignment angle on the
      hindfoot alignment view was decreased after operation in both groups but was not
      significantly different between both groups ( p = 0.410). Hindfoot alignment
      ratio was also increased after the operation in both groups, but was not
      different between two groups ( p = 0.783). CONCLUSION: The additional first ray
      osteotomy using MCOWO had no correctional power for hindfoot correction, although
      it caused improvement in some radiographic parameters.

PMID- 29185377
TI  - The painter from Sinaloa: artistic analysis of a case of spatial agnosia and
      neglect of visual shapes.
AB  - Paintings produced spontaneously by patients with neurological lesions represent
      a fascinating opportunity to analyze some aspects of the underlying disease and
      involved brain mechanisms. Many cases of artists who have suffered spatial
      neglect following a neurological disease have been reported in the literature.
      However, only a few studies evaluating the different subtypes of graphic neglect
      and aspects related to the construction of perspective (three dimensionality) in
      works of art have been published. In the present article, we present the case of
      an artist who, after resection of a central neurocytoma that affected the right
      thalamo-parietal connections, suffered an impairment of the ability to create
      perspective in his paintings and involuntary omission of only shapes in the left
      side of his paintings, although colors and contours were preserved.

PMID- 29185378
TI  - Matching Microsimulation Risk Factor Correlations to Cross-sectional Data: The
      Shortest Distance Method.
AB  - BACKGROUND: Microsimulation models often compute the distribution of a simulated
      cohort's risk factors and medical outcomes over time using repeated waves of
      cross-sectional data. We sought to develop a strategy to simulate how risk factor
      values remain correlated over time within individuals, and compare it to
      available alternative methods. METHODS: We developed a method using shortest
      distance matching for modeling changes in risk factors in individuals over time,
      which preserves both the cohort distribution of each risk factor as well as the
      cross-sectional correlation between risk factors observed in repeated cross
      sectional data. We compared the performance of the method with rank stability and
      regression methods, using both synthetic data and data from the Framingham
      Offspring Heart Study (FOHS) to simulate a cohort's atherosclerotic
      cardiovascular disease (ASCVD) risk. RESULTS: The correlation between risk
      factors was better preserved using the shortest distance method than with rank
      stability or regression (root mean squared difference = 0.077 with shortest
      distance, v. 0.126 with rank stability and 0.146 with regression in FOHS, and
      0.052, 0.426 and 0.352, respectively, in the synthetic data). The shortest
      distance method generated population ASCVD risk estimate distributions
      indistinguishable from the true distribution in over 99.8% of cases (Kolmogorov
      Smirnov, P > 0.05), outperforming some existing regression methods, which
      produced ASCVD distributions statistically distinguishable from the true one at
      the 5% level around 15% of the time. LIMITATIONS: None of the methods considered
      could predict individual longitudinal trends without error. The shortest-distance
      method was not statistically inferior to rank stability or regression methods for
      predicting individual risk factor values over time in the FOHS. CONCLUSIONS: A
      shortest distance method may assist in preserving risk factor correlations in
      microsimulations informed by cross-sectional data.

PMID- 29185379
TI  - Surgical dislocation of the hip without trochanteric osteotomy.
AB  - BACKGROUND: Surgical dislocation of the hip remains an important alternative in
      hip preservation surgery, especially when a dynamic access to the hip is needed
      and arthroscopy is not a suitable option. We describe a novel technique for
      operative dislocation of the hip without trochanteric osteotomy and the clinical
      results of our patients. METHODS: Surgical dislocation of the hip without
      trochanteric osteotomy was done through a modified lateral approach in all of the
      cases. A review of demographic, clinical, and radiological data was done in all
      of the patients operated with this technique between 2010 and 2015.
      Complications, walking aids, weight-bearing status, and modified Harris Hip Score
      (mHHS) were also recorded. RESULTS: Six surgical dislocations of the hip were
      carried out. Indications were tumor resection in five and bulletectomy in one
      hip. There were two women (four hips) and two men. Mean age was 19 +/- 3.8 years.
      Median follow-up was 2.5 years (range 2-4.5 years). Median mHHS was 92 (90-96).
      There were no intraoperative nor postoperative complications. CONCLUSIONS:
      Surgical dislocation of the hip without trochanteric osteotomy through a modified
      lateral approach appears to be a safe, simpler, and effective alternative.

PMID- 29185381
TI  - Long-term spatial clustering in free recall.
AB  - We explored the influence of space on the organisation of items in long-term
      memory. In two experiments, we asked our participants to explore a virtual
      environment and memorise discrete items presented at specific locations. Memory
      for those items was later on tested in immediate (T1) and 24 hours delayed (T2)
      free recall tests, in which subjects were asked to recall as many items as
      possible in any order. In experiment 2, we further examined the contribution of
      active and passive navigation in recollection dynamics. Results across
      experiments revealed a significant tendency for participants to consecutively
      recall items that were encountered in proximate locations during learning.
      Moreover, the degree of spatial organisation and the total number of items
      recalled were positively correlated in the immediate and the delayed tests.
      Results from experiment 2 indicated that the spatial clustering of items was
      independent of navigation types. Our results highlight the long-term stability of
      spatial clustering effects and their correlation with recall performance,
      complementing previous results collected in immediate or briefly delayed tests.

PMID- 29185380
TI  - 'We don't even have Wi-Fi': a descriptive study exploring current use and
      availability of communication technologies in residential aged care.
AB  - BACKGROUND: There has been significant growth in communication technologies.
      However, it is unknown to what extent RACFs accommodate such technologies. AIM:
      To explore the use and availability of communication technologies for use by
      residents within RACFs in Queensland, Australia. METHODS: A descriptive,
      structured telephone survey. Every 10th alphabetically listed facility from a
      total sample of n = 462 were telephoned and staff were invited to complete the
      survey. RESULTS: Forty-one out of a total of 93 RACFs completed the survey. The
      telephone was by far the primary form of communication used by residents to
      communicate with family and friends (n = 40; 97.6%). Conversely, the use of web
      connection communication software (Skype or similar) was uncommon. CONCLUSION:
      The use and availability of communication technologies is limited within RACFs,
      highlighting a significant lag in the uptake within the sector.

PMID- 29185383
TI  - Prediction of height increment using preoperative radiological parameters
      following selective thoracic fusion with alternate-level pedicle screw construct
      in Lenke 1 and 2 adolescent idiopathic scoliosis patients.
AB  - PURPOSE: This study aims to derive a formula to predict post-operative height
      increment in Lenke 1 and Lenke 2 adolescent idiopathic scoliosis (AIS) patients
      using preoperative radiological parameters. METHODS: This study involved 70
      consecutive Lenke 1 and 2 AIS patients who underwent scoliosis correction with
      alternate-level pedicle screw instrumentation. Preoperative parameters that were
      measured included main thoracic (MT) Cobb angle, proximal thoracic (PT) Cobb
      angle, lumbar Cobb angle as well as thoracic kyphosis. Side-bending flexibility
      (SBF) and fulcrum-bending flexibility (FBF) were derived from the measurements.
      Preoperative height and post-operative height increment was measured by an
      independent observer using a standardized method. RESULTS: MT Cobb angle and FB
      Cobb angle were significant predictors ( p < 0.001) of height increment from
      multiple linear regression analysis ( R = 0.784, R2 = 0.615). PT Cobb angle,
      lumbar, SB Cobb angle, preoperative height and number of fused segment were not
      significant predictors for the height increment based on the multivariable
      analysis. Increase in post-operative height could be calculated by the formula:
      Increase in height (cm) = (0.09 * preoperative MT Cobb angle) - (0.04 x FB Cobb
      angle) - 0.5. CONCLUSION: The proposed formula of increase in height (cm) = (0.09
      * preoperative MT Cobb angle) - (0.04 * FB Cobb angle) - 0.5 could predict post
      operative height gain to within 5 mm accuracy in 51% of patients, within 10 mm in
      70% and within 15 mm in 86% of patients.

PMID- 29185382
TI  - In Vitro antileishmania activity of sesquiterpene-rich essential oils from
      Nectandra species.
AB  - CONTEXT: New antileishmanias are needed because of toxicity, high cost and
      resistance problems associated with available drugs. Nectandra (Lauraceae)
      produces several classes of compounds but its essential oil has not previously
      been reported to have antileishmania activity. OBJECTIVE: We evaluated the
      cytotoxicity and antileishmania activity of essential oils from Nectandra
      amazonum Nees, N. gardneri Meisn., N. hihua (Ruiz & Pav.) Rohwer and N.
      megapotamica (Spreng.) Mez. MATERIALS AND METHODS: Nectandra oils were extracted
      from stem bark/leaves by hydrodistillation and compounds were identified by GC
      MS. Oils were tested against Leishmania infantum and L. amazonensis intracellular
      amastigotes and nitric oxide production was evaluated. Cytotoxicity was achieved
      on NIH/3T3 and J774.A1 cells for the selectivity index (SI). RESULTS AND
      DISCUSSION: Nectandra gardneri was active against L. infantum and L. amazonensis
      (IC50 =  2.7 +/- 1.3/2.1 +/- 1.06 MUg/mL) and contained 85.4% sesquiterpenes, of
      which 58.2% was intermediol. Besides low cytotoxicity (SI >11.3), N. gardneri
      induced a significant increase in NO production by L. infantum-infected
      macrophages. Nectandra hihua had the best activity on L. infantum amastigotes
      (IC50 =  0.2 +/- 1.1 MUg/mL). This oil was 89.0% sesquiterpenes, with 28.1%
      bicyclogermacrene. The two specimens of N. megapotamica had different activities
      on amastigotes. The one richer in sesquiterpenes (49.9%) was active against both
      species (IC50 =  12.5 +/- 1.4/21.3 +/- 1.2) and had phenylpropanoid E-asarone as
      the main compound (42.4%). Nectandra amazonum showed moderate activity on both
      the species (IC50 =  31.9 +/- 2.0/22.1 +/- 1.3 MUg/mL) and low selectivity (0.9 <
      SI >2.6), probably due to the major presence of beta-caryophyllene (28.5%).
      CONCLUSIONS: Our data identify compounds that can now be isolated and used for
      the development of new antileishmanias.

PMID- 29185384
TI  - Treatment of displaced flexion-type pediatric supracondylar humeral fractures in
      the prone position.
AB  - PURPOSE: This study is to report a new method to reduce and fix the displaced
      flexion-type pediatric supracondylar fracture in the prone position. METHODS: Ten
      children with displaced flexion-type supracondylar humeral fractures treated
      between 2007 and 2013 were reviewed. There were three girls and seven boys, with
      a mean age of 9.5 years. The fracture was reduced by gentle traction of the
      forearm and gradual extension of the elbow in the prone position. Two or three
      crossed Kirschner wires (K-wires) were inserted percutaneously to secure the
      fracture reduction. Radiographic evaluation included the Baumann's angle and the
      lateral humerocapitellar angle. Clinical outcomes were assessed using the Flynn's
      criteria. RESULTS: Eight children had closed reduction and percutaneous K-wire
      fixation. The other two children required open reduction through a posterior
      triceps splitting approach. The mean Baumann's angle was 70.2 degrees 
      immediately after K-wires fixation and 69.5 degrees  after 3 months later. The
      mean lateral humerocapitellar angle was 38 degrees  immediately after K-wires
      fixation and 35.5 degrees  after 3 months later. The clinical outcome was
      excellent in nine children and poor in one child by the Flynn's criteria.
      CONCLUSION: Reduction of displaced flexion-type pediatric supracondylar humeral
      fractures by traction and gradual extension in the prone position is an effective
      and safe method. When reduction is still impossible or nerve incarceration is
      suspected, open reduction and release of the trapped nerve through a posterior
      triceps splitting approach are simply accessible.

PMID- 29185385
TI  - ?
AB  - :?:?: PubMed, Scopus, Wiley ?:14, ?, , , , ?, , , ?, , ?:, ?.

PMID- 29185386
TI  - Speech perception of Chinese-speaking cochlear implantees.

PMID- 29185387
TI  - Latest developments in innovative manufacturing to combine nanotechnology with
      healthcare.

PMID- 29185388
TI  - alpha-Lipoic acid, functional fatty acid, as a novel therapeutic alternative for
      central nervous system diseases: A review.
AB  - OBJECTIVES: alpha-lipoic acid (ALA) is a natural antioxidant which acts as a
      cofactor of bioenergetic mitochondrial enzymes. Along with its mitochondrial
      action, ALA and its reduced form have many biological functions resulting in a
      wide variety of actions such as anti-inflammation and antioxidant protection,
      scavenging reactive oxygen species, regenerating other antioxidant agents, such
      as vitamins C and E, and cytosolic glutathione, chelating the transitional metal
      ions (e.g. iron and copper), and modulating the signal transduction of nuclear
      factor. METHODS: By selecting papers from PubMed, Science Direct, EBSCO, and
      databases, this review discusses the biochemical properties of LA, its mechanism
      of action, pharmacokinetics, and its possible therapeutic role in central nervous
      system diseases, such as Alzheimer's disease, Parkinson's disease, Multiple
      sclerosis, stroke, and spinal cord injury. RESULTS: ALA as an antioxidant and
      anti-inflammation agent has therapeutical effects on central nervous system
      diseases, especially multiple sclerosis and PD. DISCUSSION: ALA can be considered
      as a potentially useful treatment in central nervous disorders.

PMID- 29185389
TI  - N-acetyl-L-tryptophan, a substance-P receptor antagonist attenuates aluminum
      induced spatial memory deficit in rats.
AB  - Neuroinflammation plays an important role in the pathophysiology of Alzheimer's
      disease. Neurokinin substance P is a key mediator which modulates
      neuroinflammation through neurokinin receptor. Involvement of substance P in
      Alzheimer's disease is still plausible and various controversies exist in this
      hypothesis. Preventing the deleterious effects of substance P using N-acetyl-L
      tryptophan, a substance P antagonist could be a promising therapeutic strategy.
      This study was aimed to evaluate the effect of N-acetyl-L-tryptophan on aluminum
      induced spatial memory alterations in rats. Memory impairment was induced using
      aluminum chloride (AlCl3) at a dose of 10 mg/kg for 42 d. After induction of
      dementia, rats were exposed to 30 and 50 mg/kg of N-acetyl-L-tryptophan for 28 d.
      Spatial memory alterations were measured using Morris water maze.
      Acetylcholinesterase activity and antioxidant enzyme glutathione level were
      assessed in hippocampus, frontal cortex and striatum. The higher dose of N-acetyl
      L-tryptophan (50 mg/kg) significantly improved the aluminum induced memory
      alterations. N-acetyl-L-tryptophan exposure resulted in significant increase in
      acetylcholinesterase activity and glutathione level in hippocampus. The
      neuroprotective effect of N-acetyl-L-tryptophan could be due to its ability to
      block substance P mediated neuroinflammation, reduction in oxidative stress and
      anti-apoptotic properties. To conclude, N-acetyl-L-tryptophan may be considered
      as a novel neuroprotective therapy in Alzheimer's disease.

PMID- 29185391
TI  - Current status of immunotherapy for sarcomas.
AB  - Although the development of anticancer drugs has improved the outcomes of bone
      and soft tissue sarcomas, the clinical outcome of patients with relapsed sarcomas
      remains unsatisfactory due to therapeutic toxicities and resistance to anticancer
      drugs. Therefore, novel therapeutic modalities are needed to improve the outcome
      of patients with bone and soft tissue sarcomas. Dendritic cells present tumor
      antigens and stimulate immune responses, and immune cells, such as cytotoxic T
      lymphocytes, kill tumor cells by recognizing tumor antigens. However, immune
      suppressive conditions by immune regulator PD-1, CTLA-4 and regulatory T cells
      help tumor growth and progression. In this report, current immunotherapies
      including cellular immunotherapy and checkpoint inhibitors are introduced, and
      the advantages and disadvantages of the treatments are discussed.

PMID- 29185392
TI  - Immunotherapy in head and neck cancer: evidence and perspectives.
AB  - Head and neck squamous cell carcinomas evade immune response through multiple
      immunologic resistance mechanisms. Two of the most commonly involved checkpoint
      inhibitory mechanisms are CTLA-4 and PD-1/PD-L1, which act at earlier and later
      stages of immune response to tumors. Pembrolizumab and nivolumab are PD-1
      antibodies that interrupt the immunosuppressive pathway of inhibitory
      checkpoints, which are used by tumor cells to prevent immune reaction. Both
      recently gained US FDA approval for the treatment of patients with recurrent or
      metastatic head and neck cancer with disease progression during or following
      platinum containing chemotherapy. No conclusions can be drawn on the role of PD
      L1 in identifying patients responding to immunotherapy, given that similar
      studies lead to contrasting results. It will be crucial to identify predictive
      markers of immunotherapy response, and to evaluate them prospectively. A better
      understanding of the complex network between tumor, immune system and other
      oncologic treatments will help us to develop more efficient multimodality
      treatments.

PMID- 29185390
TI  - Modulation of antitumor immunity with histone deacetylase inhibitors.
AB  - Histone deacetylase inhibitors possess a broad array of antitumor activities;
      however, their net impact on the evolving antitumor immune response is highly
      dependent on the inhibitors used and the histone deacetylases they target.
      Herein, we sequentially focus on each stage of the antitumor immune response -
      from dendritic cell activation and migration, antigen uptake and presentation, T
      cell activation and differentiation and the enactment of antitumor effector
      functions within the tumor microenvironment. In particular, we will discuss how
      various inhibitors have different effects depending on cellular activation,
      experimental design and specific histone deacetylases being targeted - and how
      these changes impact the outcome of an antitumor immune response. At last, we
      consider the impact these inhibitors may have on T-cell exhaustion and
      implications for combination with other immunomodulating therapies.

PMID- 29185393
TI  - Chimeric switch receptor: switching for improved adoptive T-cell therapy against
      cancers.
AB  - Adoptive T-lymphocyte transfer-based immunotherapy for cancers has seen huge
      leaps with both CARs and engineered TCRs. Despite this, issues relating to safety
      and efficacy persist. To address this, chimeric switch receptors have been
      created to reverse the outcomes of their original signaling pathways in order to
      confer immune cells with the ability to overcome the immunosuppressive tumor
      microenvironment and to allow them to have greater in vivo persistence.
      Activating switch receptors exploit the inhibitory molecules expressed by cancer
      cells to further stimulate the tumor antigen-specific T lymphocytes. On the other
      hand, inhibitory switch receptors inhibit the effects of tumor-reactive T
      lymphocytes on unintended targets. This paper reviews the switch receptors
      reported thus far, and lists out potential improvements and future works.

PMID- 29185394
TI  - Modulation of immunosurveillance by tumor-intrinsic genomic alterations.

PMID- 29185396
TI  - New Directions for Dementia.

PMID- 29185395
TI  - PD-L1 expression in tumor metastasis is different between uveal melanoma and
      cutaneous melanoma.
AB  - AIM: To compare PD-L1 expression between metastatic uveal melanoma (MUM) and
      metastatic cutaneous melanoma (MCM). MATERIALS & METHODS: A total of 295 MCM and
      78 MUM specimens were analyzed for tumor cell PD-L1 expression. Additionally, 91
      MCM and 45 MUM specimens were analyzed for PD-1 expression on tumor-infiltrating
      lymphocytes. RESULTS: A total of 77/295 (26.1%) MCM specimens expressed PD-L1 as
      compared to 4/78 (5.1%) MUM specimens (p < 0.0001). PD-1 expression on tumor
      infiltrating lymphocytes was greater in MCM (73.6%; 67/91) than in MUM (51.1%;
      23/45), respectively (p = 0.009). CONCLUSION: Significant differences exist in PD
      L1 expression between MCM and MUM. The lower PD-L1 expression in MUM may provide
      a rationale for failure of PD-1 inhibitor therapy and suggests that immune
      evasion in this disease may occur via alternative mechanisms.

PMID- 29185397
TI  - A Suggested Plan for Specialist Doctor's Professional Growth and Development.

PMID- 29185398
TI  - Diaphragmatic Excursion: Does it Predict Successful Weaning from Mechanical
      Ventilation?
AB  - OBJECTIVE: To measure the diaphragmatic excursion and its outcome on weaning from
      mechanical ventilation. STUDY DESIGN: Cross-sectional comparative study. PLACE
      AND DURATION OF STUDY: Medical Intensive Care Unit (ICU), Military Hospital (MH),
      Rawalpindi, Pakistan, from January to December 2014. METHODOLOGY: Diaphragmatic
      excursion (DE) in cm was measured through ultrasound by marking liver and spleen
      displacement in patients who fulfilled the criteria of removal from ventilatory
      support. The patients were followed up for 48 hours and classified according to
      the outcome as successful weaning and weaning failure. RESULTS: Out of 100 cases,
      76 patients had a successful weaning while 24 had a failed weaning outcome. At a
      diaphragmatic excursion of 1.2 cm and more, out of 67 cases, 60 had a successful
      weaning (89.55%) while 7 cases (10.45%) had a weaning failure. At an excursion of
      less than 1.2 cm, 17 out of 33 cases (51.5%) had successful weaning while 16
      (48.48%) had weaning failure. At this cut off point (1.2 cm), the sensitivity and
      specificity for successful weaning were 78.95% and 70.83%, respectively. The
      positive and negative likelihood ratio (LR) for these values being 2.70 and 0.29,
      respectively. The positive predictive value was 82.35% and negative predictive
      value 60.00%. CONCLUSION: Ultrasonographic measurement of diaphragmatic excursion
      is a good method for predicting weaning outcome from mechanical ventilation.

PMID- 29185399
TI  - Negative Predictive Value of Ultrasound in Predicting Tumor-Free Margins in
      Specimen Sonography.
AB  - OBJECTIVE: To evaluate the success of ultrasound in post-excision specimen
      visualization, and negative predictive value of ultrasound for estimation of
      tumor-free margins using histopathology as the gold standard. STUDY DESIGN: Cross
      sectional analytical study. PLACE AND DURATION OF STUDY: The Aga Khan University
      Hospital, Karachi, Pakistan, from May 2010 till January 2013. METHODOLOGY:
      Sonography of all breast nodules was done before and after exicision by two
      female radiologists with at least five years clinical experience. All surgeries
      were performed by the same referring breast surgeons. All nodules were non
      palpable and had histopathology as well as specimen sonography performed at AKUH.
      Subjects were excluded, if histopathology was not available, post-procedure
      sonogram not done or done in another hospital and nodules that were not seen on
      ultrasound. After needle localization in 47 patients using ultrasound and in 7
      patients using mammogram was done, sonogram was conducted in all 54 lesions.
      These were then assessed by ultrasound for detection of lesion and tumor-free
      margins in malignant lesion. Post-excision ultrasound was performed for the
      evaluation of lesion whether visualized or absent with localizing needle in situ,
      lesion dimensions, depth measurement between the superior margin of the lesion
      and its edge. RESULTS: All 54 lesions were present on post-exicison scan, out of
      which 28 were documented as malignant and 26 as benign. Ultrasound declared all
      specimens as tumor-free. On histopathology, two lesions were documented as having
      tumor-positive margins and were proven to be invasive lobular carcinoma.
      Therefore, the negative predictive value of the specimen sonography for margin
      detection was 26/28 (92.8%). CONCLUSION: Ultrasound of the excised breast tumor
      specimen is a simple and reliable technique for confirmation of the tumor-free
      margins in non-palpable breast lesions.

PMID- 29185400
TI  - Safety of Trans-Nasal Percutaneous Endoscopic Gastrostomy Placement.
AB  - OBJECTIVE: To evaluate the safety of trans-nasal percutaneous endoscopic
      gastrostomy (TPEG) placement for nutrition in patients where oral approach is not
      possible. STUDY DESIGN: Case-series. PLACE AND DURATION OF STUDY: April 2010 to
      April 2016 in the Department of Gastroenterology at Liaquat National Hospital,
      Karachi. METHODOLOGY: Patients underwent trans-nasal PEG placement and were
      included in this study. Inclusion criteria were either gender of any age and
      patients referred for PEG tube placement in whom oral PEG tube insertion was not
      possible. Ultrathin gastroscope (outer diameter of 5.9 mm) was passed through a
      nostril after assessment and lubrication, the pull technique was used for tube
      placement. Primary outcome variable of study was the safety of the procedure. The
      secondary outcome variables were procedure related complications during and 72
      hours after the procedure. RESULTS: TPEG placement was successful in all 46
      cases. Thirty-one (67.4%) were males. The mean age was 56.63 +/-12.62 years.
      Dysphagia was the main indication in all cases. Head and neck cancer was the most
      common indication present in 38 (82.6%) patients. In 36 (78.2%) cases, the
      procedure was performed under local anesthesia. PEG site infection occurred in
      one (2.1%) patient. CONCLUSION: TPEG is a safe procedure in patients with oro
      pharyngeal obstruction, and it should be considered as an alternative approach.

PMID- 29185401
TI  - Improvement in Therapeutic Ability of Wharton's Jelly Derived Mesenchymal Stem
      Cells with Vitamin E in Breast Cancer.
AB  - OBJECTIVE: To assess the role of Vitamin E to improve the survival of Wharton's
      jelly derived mesenchymal stem cells (WJMSCs) in breast cancer conditions. STUDY
      DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Centre for Research
      in Molecular Medicine, University of Lahore, from November 2016 to March 2017.
      METHODOLOGY: WJMSCs were obtained from umbilical cord tissue with enzyme
      digestion method. Isolated cells were characterized for CD90 and CD45 by
      immunocytochemistry. Pretreatment and conjugation therapies of vitamin E in 50mM
      and 100mM concentration were used on WJMSCs and breast cancer plasma was provided
      to mimic the cancer conditions, while WJMSCs provided with normal plasma were
      considered control. Cells' viability, proliferation and death were evaluated by
      crystal violet staining, MTT assay and LDH assay, respectively. Oxidative stress
      was observed by activity of anti-oxidant enzymes (GSH, catalase, SOD) and
      reactive oxygen species (MDA). RESULTS: The isolated cells expressed mesenchymal
      stem cells marker CD90 and lacked hematopoietic marker CD45. Vitamin E improved
      the viability and proliferation of WJMSCs in normal plasma, in conjugation with
      breast cancer plasma and in pretreatment groups but conjugation group showed even
      better results with concentration of 100mM as compared to the pretreatment group
      and opposite was observed for LDH assay for cells death analysis. Vitamin E also
      reduced the oxidative stress in 100mM more pronounced in conjugation group as
      compared to pretreatment group while left no harmful effects on WJMSCs in normal
      plasma. CONCLUSION: Vitamin E conjugation with breast cancer conditions
      significantly improved growth of WJMSCs. Thus vitamin E treated WJMSCs are better
      therapeutic options for breast cancer.

PMID- 29185402
TI  - Hearing Status after Radical Mastoidectomy without Tympanoplasty.
AB  - OBJECTIVE: To find out the impairment of hearing associated with radical
      mastoidectomy by measuring the quantitative difference in the functional hearing
      level before and after radical mastoidectomy operation without tympanoplasty.
      STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY:
      Department of Otorhinolaryngology and Head Neck Surgery, Bahawal Victoria
      Hospital, Bahawalpur and PNS Shifa Hospital, Karachi, from November 2009 to
      January 2013. METHODOLOGY: Eighty-five patients, diagnosed clinically as chronic
      suppurative otitis media with extensive cholesteatoma having history of ear
      discharge and hearing impairment for more than 6 weeks duration and requiring
      radical mastoidectomy for treatment, were included in this study. Pure tone
      audiogram was done before and after radical mastoidectomy. Hearing impairment was
      compared in each patient before and after the operation. RESULTS: Among the 85
      patients, 54 (63.5%) were males and 31 (36.5%) were females, with the age ranged
      between 18 to 63 years, mean age being 42.31 4.8 years. The mean increase in
      hearing loss after radical mastoidectomy in air conduction was 7.19 dB, bone
      conduction was 4.16 dB, and air-bone gap was 3.75 dB (0.001). The ear became dry
      and safe in 82 patients (96.5%) out of a total of 85, and only 3 patients
      required revision surgery at a second stage. CONCLUSION: Radical mastoidectomy
      has a least negligible effect on hearing status and one should not limit this
      technique due to the concern of aggravated hearing in patients with extensive
      cholesteatoma at the cost of dry and safe ears, which should be of prime
      importance.

PMID- 29185403
TI  - Effect of Femtosecond Laser-Assisted Cataract Surgery (FLACS) on Endothelial Cell
      Count.
AB  - OBJECTIVE: To compare the change in endothelial cell count after femtosecond
      laser-assisted cataract surgery (FLACS) versus conventional phacoemulsification.
      STUDY DESIGN: Randomized controlled clinical trial. PLACE AND DURATION OF STUDY:
      Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan from January 2016
      to August 2017. METHODOLOGY: Patients with senile cataract and age ranging from
      40 to 80 years were included in the study. Patients with any other cause of
      endothelial cell loss, history of trauma, documented diabetes millitis,
      hypertention and glaucoma were excluded. Preoperative detailed ocular
      examination, including both anterior and posterior examination, was carried out.
      Patients were distributed into two groups. Group GP were planned for conventional
      phacoemulsification, while group GF underwent FLACS. All the surgeries were
      performed under local anesthesia by same ophthalmic surgeon. Specular microscope
      (Topcon specular microscope sp-3000p) was utilized to measure the endothelial
      cell count (ECC) before and 4 weeks after the surgery. RESULTS: Fifty eyes (25 in
      each group) of 48 patients underwent cataract surgery by phacoemulsification or
      FLACS. Twenty-five (52.08%) out of the total were females while 23 (47.91%) were
      males. Median age of the participants in phacoemulsification group was 55 years
      (IQR 20.50), while in FLACS group it was 54 years (IQR 8). The median change in
      endothelial cell count was 228 (IQR 532) in Phaco group, while 23 (IQR 35) in
      FLACS group. (p<0.05 Mann Whitney U-test). CONCLUSION: FLACS is a safe and
      effective modality for cataract treatment and it induces significantly less
      endothelial cell loss than conventional phacoemulsification.

PMID- 29185404
TI  - High Burden of Subclinical Lead Toxicity after Phase Out of Lead from Petroleum
      in Pakistan.
AB  - OBJECTIVE: To evaluate the frequency of subclinical lead toxicity. STUDY DESIGN:
      Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Pathology and
      Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011
      to December 2014. METHODOLOGY: Analysis of laboratory data for blood lead levels
      (BLL) was performed. Lead was tested by atomic absorption spectrometer. For all
      subjects, only initial test results were included while the results of repeated
      testing were excluded. Exemption was sought from institutional ethical review
      committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively
      were taken as subclinical lead toxicity. RESULTS: Amongst the total number of
      subjects tested (n=524), 26.5% (n=139) were children (<16 years) while rest were
      adults. Overall median BLLs was 6.4 ug/dl (20.9-3.1). The median BLL was 4 ug/dl
      (6.7-2.6) in children and 8.3 ug/dl (27.9-3.4) in adults, respectively. The BLL
      increased with age; higher levels were observed in age range 21-30 years of
      subjects [median lead level 16.9 ug/dl (36.1-4)] and lower level [4.2 ug/dl (6.8
      2.6)] in children with <10 years of age. Only 16% (n=22) children had desirable
      lead levels while most had either subclinical (76%, n=106) or toxic lead levels
      (8%, n=11). In adults, (55%, n=212) subjects had desired lead levels, and 40%
      (n=154) and 4.99% (n=19) had subclinical and toxic lead levels. CONCLUSION:
      Presence of subclinical lead poisoning even after phasing out of lead petroleum
      in Pakistanis is alarming, especially in children. A national population-based
      study to determine the lead status and targeted intervention to identify
      potential sources is need of the time.

PMID- 29185405
TI  - Effect of Lidocaine 2% on Bacterial Culture of Bronchial Fluid.
AB  - OBJECTIVE: To evaluate the action of 2% lidocaine on the culture results of
      bronchial fluid in patients suspected of having lower respiratory tract
      infections. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF
      STUDY: Shahid Sadoughi Hospital, Yazd, Iran, from November 2014 to November 2015.
      METHODOLOGY: Patients suspected of lower respiratory tract infections referred to
      bronchoscopy unit of the Hospital were included. Those with incomplete
      questionnaire and bronchoscopy contraindication were excluded. Bronchial fluid
      was aspirated before and after local application of 2% lidocaine and cultured,
      according to the suspected clinical diagnosis. Finally, statistical analysis was
      performed using SPSS software, version 17.0. For statistical comparisons,
      McNemar's test was used. Level of significance was kept at p <0.05. RESULTS: The
      mean age of the study population was 51.83 +/-15.93 with a range of 25 - 80
      years. Out of 130 patients, 60 patients had positive culture results. Nineteen
      (31.7%) cases had positive culture for tuberculosis and 41 (63.3%) cases had
      positive results for other bacteria before intervention that did not change after
      using 2% lidocaine (p=1). In 70 (53.84%) cases, results were negative before and
      after use of 2% lidocaine. CONCLUSION: No significant difference was found
      between culture results before and after the use of lidocaine. Therefore,
      lidocaine can be used during bronchoscopy to increase patient tolerance.

PMID- 29185406
TI  - Anaesthetic Management of Supratentorial Tumor Craniotomy Using Awake-Throughout
      Approach.
AB  - The authors are reporting an anaesthetic management of patient presenting with
      left parietal lobe space occupying lesion and scheduled for Awake-craniotomy.
      Awake-throughout approach using scalp block was planned. Among techniques
      reported for keeping patient awake during the surgery, this one is really
      underutilized. The successful conduct requires thorough preoperative assessment
      and psychological preparation. We used powerpoint presentation as a preoperative
      teaching tool. The anatomical landmark technique was used to institute scalp
      block, where individual nerves were targeted bilaterally. Patient remained stable
      throughout and participated actively in intraoperative neurological monitoring.
      Postoperative period showed remarkable recovery, better pain control, and shorter
      length of stay in hospital.

PMID- 29185407
TI  - Duodenal Perforation due to Ingested Partial Denture.
AB  - Ingestion of foreign bodies including dentures can be a cause of morbidity and
      mortality. We report a case of poor-fit denture in an elderly male with pulmonary
      and musculoskeletal comorbidities, who presented as an acute abdomen. The pin
      attached to the denture caused perforation of first part of duodenum. The only
      positive finding prior to surgery was a radiopaque density in the abdominal
      radiograph of the patient and air under the diaphragm. It is important for all
      the surgeons dealing with acute care patients to be aware of different designs
      and constructions of dentures.

PMID- 29185408
TI  - High Altitude Retinopathy Presenting as Central Retinal Vein Occlusion in a
      Soldier.
AB  - A 33-year soldier, deployed at an altitude of 3,350 meters for two years,
      developed unilateral Central Retinal Vein Occlusion (CRVO) in the left eye. He
      had no risk factor for thrombosis and all thrombophilia screenings were negative.
      The patient was managed with intravitreal injections of anti-VEGF (Bevacizumab)
      every four weeks. He showed gradual improvement in the visual acuity over the
      next 3 months. Best corrected visual acuity (BCVA) after three months was 6/7.5;
      whereas, initially it was limited to hand movements only. This case illustrates
      that prolonged exposure to high altitude is a risk factor for CRVO, too. Frequent
      eye examination, including fundus, should be carried out among people living at
      such altitudes.

PMID- 29185409
TI  - Transient Methemoglobinemia in three Neonates due to Maternal Pudendal
      Anesthesia.
AB  - Methemoglobin (MetHb) is a form of hemoglobin which contains iron in ferric
      state. The delivery of oxygen to tissues is impaired and cellular hypoxia
      develops with an increase in MetHb levels. Methemoglobinemia is a rare but
      potentially lethal complication of local anesthetics. In this clinical brief,
      three cases of transient neonatal methemoglobinemia, caused by maternal pudendal
      anesthesia with prilocaine, are reported.

PMID- 29185410
TI  - Parvovirus B19: A Rare Cause of Post-renal Transplant Anemia.
AB  - Parvovirus B19 infection should be contemplated as one of the differential
      diagnoses of persistent anemia in transplanted patients. There must be high index
      of suspicion of Parvovirus B19, when post-transplant patients present with
      refractory and severe anemia with reticulocytopenia and all the other common
      causes of anemia such as blood loss, adverse effects of immunosuppressant agents
      and graft dysfunction has been ruled out. In suspected patients, diagnosis is
      confirmed by serological tests (IgM and IgG), PCR from blood and/or bone marrow
      and by bone marrow biopsy finding of pure red cell aplasia. Intravenous
      immunoglobulin (IVIG) is the treatment of choice and highly rewarding. Here we
      are reporting two cases of post-transplant Parvovirusinfection, one in an adult
      lady and second in an adult man who underwent live renal transplantation
      recently.

PMID- 29185411
TI  - Predicament in Detection and Reporting of Extended Spectrum Beta Lactamase
      Production in Routine Antibiotic Susceptibility Testing.
AB  - This descriptive and cross-sectional study was planned to determine the dilemma
      of inadvertent detection of extended spectrum beta lactamase (ESBL) production in
      Enterobacteriaceaewhen using inhibition zone size of antibiotic disks of
      Cefotaxime or Aztreonam in routine antibiotic susceptibility testing as
      recommended by Clinical Laboratory Standards Institute (CLSI). Screening and
      double disk tests were adopted as per CLSI. Escherichia coli ATCC 25922 was used
      as control strain. Among total specimens of 5346, there were 348 isolates of
      Escherichia coli(n=235), Klebsiella pneumonia (n=92), Klebsiella oxytoca(n=3) or
      Proteus mirabilus(n=18). The screening method recommended by CLSI significantly
      falsely detected ESBL production in 79 (32.3%) isolates (p<0.0001). ESBL
      detection is important as its frequency is high and treatment of the infection
      varies with the presence and absence of ESBL. To avoid false reporting, proper
      phenotypic detection of ESBL confirmatory method-like double-disk synergy test,
      should be used routinely.

PMID- 29185412
TI  - LIFT Techniue for Simple Rectovaginal Fistula

PMID- 29185413
TI  - Mucoepidermoid Carcinoma in a 62-Year Female.

PMID- 29185414
TI  - Superficial Angiomyxoma of Palate.

PMID- 29185415
TI  - Reliability of Vancomycin Sensitivity Assays for Staphylococcus Aureus.

PMID- 29185416
TI  - In-Utero Bilious Vomiting Resembling Meconium Stainedlike Liquor may be an
      Indication of Distal Intestinal Obstruction.

PMID- 29185417
TI  - Integrating Rehabilitation Physicians in Stroke Rehabilitation Challenges in
      Pakistan.

PMID- 29185418
TI  - Making Local Anesthesia Delivery More Comfortable.

PMID- 29185420
TI  - Extreme weather in 2017: time to take climate change seriously.

PMID- 29185419
TI  - Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis
      during asymmetric cell division.
AB  - Asymmetric division generates cellular diversity by producing daughter cells with
      different fates. In animals, the mitotic spindle aligns with Par complex
      polarized fate determinants, ensuring that fate determinant cortical domains are
      bisected by the cleavage furrow. Here, we investigate the mechanisms that couple
      spindle orientation to polarity during asymmetric cell division of Drosophila
      neuroblasts. We find that the tumor suppressor Discs large (Dlg) links the Par
      complex component atypical Protein Kinase C (aPKC) to the essential spindle
      orientation factor GukHolder (GukH). Dlg is autoinhibited by an intramolecular
      interaction between its SH3 and GK domains, preventing Dlg interaction with GukH
      at cortical sites lacking aPKC. When co-localized with aPKC, Dlg is
      phosphorylated in its SH3 domain which disrupts autoinhibition and allows GukH
      recruitment by the GK domain. Our work establishes a molecular connection between
      the polarity and spindle orientation machineries during asymmetric cell division.

PMID- 29185421
TI  - Immunological profiling to assess disease severity and prognosis in community
      acquired pneumonia.

PMID- 29185422
TI  - Corrections.

PMID- 29185423
TI  - Caring for migrant health-care workers.

PMID- 29185424
TI  - Pledge deaths in US colleges.

PMID- 29185426
TI  - Offline: Who is Peter Sands?

PMID- 29185425
TI  - Why do so many clinical trials of therapies for Alzheimer's disease fail?

PMID- 29185427
TI  - Scotland to implement alcohol pricing legislation.

PMID- 29185428
TI  - Peter Sands appointed head of the Global fund.

PMID- 29185429
TI  - Agnes Buzyn: France's Minister for Solidarity and Health.

PMID- 29185430
TI  - Pembrolizumab is effective for drug-resistant gestational trophoblastic
      neoplasia.

PMID- 29185431
TI  - Comment on the PODCAST study.

PMID- 29185432
TI  - Comment on the PODCAST study - Authors' reply.

PMID- 29185433
TI  - Focus on RNA interference: from nanoformulations to in vivo delivery.

PMID- 29185434
TI  - The unique contribution of Professor Lars E Gustafsson to the field of breath
      research.

PMID- 29185435
TI  - Terahertz spectral unmixing based method for identifying gastric cancer.
AB  - At present, many researchers are exploring biological tissue inspection using
      terahertz time-domain spectroscopy (THz-TDS) techniques. In this study, based on
      a modified hard modeling factor analysis method, terahertz spectral unmixing was
      applied to investigate the relationships between the absorption spectra in THz
      TDS and certain biomarkers of gastric cancer in order to systematically identify
      gastric cancer. A probability distribution and box plot were used to extract the
      distinctive peaks that indicate carcinogenesis, and the corresponding weight
      distributions were used to discriminate the tissue types. The results of this
      work indicate that terahertz techniques have the potential to detect different
      levels of cancer, including benign tumors and polyps.

PMID- 29185436
TI  - Objective image characterization of a spectral CT scanner with dual-layer
      detector.
AB  - This work evaluated the performance of a detector-based spectral CT system by
      obtaining objective reference data, evaluating attenuation response of iodine and
      accuracy of iodine quantification, and comparing conventional CT and virtual
      monoenergetic images in three common phantoms. Scanning was performed using the
      hospital's clinical adult body protocol. Modulation transfer function (MTF) was
      calculated for a tungsten wire and visual line pair targets were evaluated. Image
      noise power spectrum (NPS) and pixel standard deviation were calculated. MTF for
      monoenergetic images agreed with conventional images within 0.05 lp cm-1. NPS
      curves indicated that noise texture of 70 keV monoenergetic images is similar to
      conventional images. Standard deviation measurements showed monoenergetic images
      have lower noise except at 40 keV. Mean CT number and CNR agreed with
      conventional images at 75 keV. Measured iodine concentration agreed with true
      concentration within 6% for inserts at the center of the phantom. Performance of
      monoenergetic images at detector based spectral CT is the same as, or better
      than, that of conventional images. Spectral acquisition and reconstruction with a
      detector based platform represents the physical behaviour of iodine as expected
      and accurately quantifies the material concentration.

PMID- 29185437
TI  - Hierarchy and scaling behavior of multi-rank domain patterns in ferroelectric
      K0.9Na0.1NbO3 strained films.
AB  - The formation process of a ferroelectric multi-rank domain pattern in the
      thickness range of 7-52 nm is investigated for monoclinic K0.9Na0.1NbO3 strained
      epitaxial films on (110) NdScO3 substrates. Although the elastic strain energy
      density is degenerated for two pseudocubic orientations, a distinctive hierarchy
      of domain evolution is observed with exclusive in-plane a1a2 domains for very
      thin films and the retarded onset of a ferroelectric MC phase at larger film
      thickness. This is accompanied by a thickness dependent transformation from
      stripe domains to a herringbone pattern and, eventually, for the thickest film,
      to a checkerboard-like structure. These transformations in the domain arrangement
      and width are correlated to energetic aspects as depolarization field and
      anisotropic strain relaxation in the film. While for the MC domains plastic
      strain relaxation is throughout observed, the a1a2 domains show a two-step strain
      relaxation mechanism starting with an in-plane elastic shearing, which is
      followed by plastic lattice relaxation. Our results highlight a pathway for
      engineering and patterning of periodic ferroelectric domain structures.

PMID- 29185438
TI  - Emerging optical properties from the combination of simple optical effects.
AB  - Structural color arises from the patterning of geometric features or refractive
      indices of the constituent materials on the length-scale of visible light. Many
      different organisms have developed structurally colored materials as a means of
      creating multifunctional structures or displaying colors for which pigments are
      unavailable. By studying such organisms, scientists have developed artificial
      structurally colored materials that take advantage of the hierarchical
      geometries, frequently employed for structural coloration in nature. These
      geometries can be combined with absorbers-a strategy also found in many natural
      organisms-to reduce the effects of fabrication imperfections. Furthermore,
      artificial structures can incorporate materials that are not available to nature
      in the form of plasmonic nanoparticles or metal layers-leading to a host of novel
      color effects. Here, we explore recent research involving the combination of
      different geometries and materials to enhance the structural color effect or to
      create entirely new effects, which cannot be observed otherwise.

PMID- 29185439
TI  - A survey on the pattern of dermoscopy use among dermatologists in India.
AB  - INTRODUCTION AND BACKGROUND: Dermoscopy is being increasingly used for improving
      dermatological diagnosis. Use of dermoscopy in the early recognition of skin
      malignancies, especially melanoma, is well established. Of late, its use in
      general clinical dermatology is growing with the recognition of new and specific
      patterns in conditions such as hair disorders, inflammatory disorders, and
      infections/infestations. This cross-sectional survey aims to assess the common
      patterns of dermoscopy use by Indian dermatologists. METHODS: This was across
      sectional survey. An online questionnaire was used to collect data. The
      questionnaire focused on the frequency of dermoscopy use by Indian
      dermatologists, reasons for using it or not, and the training they had received
      on dermoscopy. RESULTS: Of the total 150 valid responses, eighty two (54.7%)
      participants reported that they were using dermoscopy routinely in their clinical
      practice. Lack of familiarity and lack of proper training were the important
      reasons cited for not using dermoscopy regularly. Among the dermatologists using
      dermoscopy, consensus on effectiveness was highest for hair disorders.
      CONCLUSIONS: Dermoscopy use by dermatologists in India is mainly in the context
      of inflammatory dermatosis and hair disorders rather than skin tumors. Lack of
      familiarity with the technique appears to be main factor limiting the use of
      dermoscopy in India. LIMITATIONS: Small sample size is the major limitation of
      this study. It is possible that a large number of dermatologists who do not use
      dermoscopy might not have responded to the survey, there by affecting the results
      and their interpretation.

PMID- 29185440
TI  - Risk of venous thromboembolism in patients with bullous pemphigoid: A systematic
      review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Increased risk of venous thromboembolism is observed
      in several autoimmune inflammatory disorders. However, data on bullous
      pemphigoid, one of the most common autoimmune blistering disorders, is limited.
      This systematic review and meta-analysis was conducted to summarize all available
      evidence. METHODS: Two investigators independently searched published studies
      indexed in MEDLINE and EMBASE from inception to July 2016 using the terms for
      bullous pemphigoid and venous thromboembolism. The inclusion criteria were as
      follows: (1) cohort or case-control study evaluated the association between
      bullous pemphigoid and risk of venous thromboembolism, (2) effect estimates were
      provided as odds ratios, relative risk, hazard ratio, standardized incidence
      ratio with 95% confidence intervals, and (3) subjects without bullous pemphigoid
      were used as comparators for cohort studies, while subjects without venous
      thromboembolism were used as comparators for case-control studies. Point
      estimates and 95% confidence intervals were extracted from each study and were
      pooled together using the random-effect model, generic inverse variance method of
      DerSimonian and Laird. Cochran's Q test and the I2 statistic were used to
      evaluate the statistical heterogeneity. RESULTS: Two retrospective cohort
      studies, one prospective cohort study, and one case-control study met the
      eligibility criteria and were included in the meta-analysis. The pooled odds
      ratio was 2.69 (95% confidence interval, 1.79-4.05). Statistical heterogeneity
      was high with I2 of 77%. LIMITATION: Limited accuracy of diagnosis of primary
      studies and high between-study heterogeneity. CONCLUSION: This meta-analysis
      demonstrated that patients with bullous pemphigoid have a significantly increased
      risk of venous thromboembolism.

PMID- 29185441
TI  - Intracellular localization of nanoparticle dimers by chirality reversal.
AB  - The intra- and extracellular positioning of plasmonic nanoparticles (NPs) can
      dramatically alter their curative/diagnostic abilities and medical outcomes.
      However, the inability of common spectroscopic identifiers to register the events
      of transmembrane transport denies their intracellular vs. extracellular
      localization even for cell cultures. Here we show that the chiroptical activity
      of DNA-bridged NP dimers allows one to follow the process of internalization of
      the particles by the mammalian cells and to distinguish their extra- vs intra
      cellular localizations by real-time spectroscopy in ensemble. Circular dichroism
      peaks in the visible range change from negative to positive during transmembrane
      transport. The chirality reversal is associated with a spontaneous twisting
      motion around the DNA bridge caused by the large change in electrostatic
      repulsion between NPs when the dimers move from interstitial fluid to cytosol.
      This finding opens the door for spectroscopic targeting of plasmonic nanodrugs
      and quantitative assessment of nanoscale interactions. The efficacy of dichroic
      targeting of chiral nanostructures for biomedical applications is exemplified
      here as photodynamic therapy of malignancies. The efficacy of cervical cancer
      cell elimination was drastically increased when circular polarization of incident
      photons matched to the preferential absorption of dimers localized inside the
      cancer cells, which is associated with the increased generation of reactive
      oxygen species and their preferential intracellular localization.

PMID- 29185442
TI  - Synergistic gene expression during the acute phase response is characterized by
      transcription factor assisted loading.
AB  - The cytokines interleukin 1beta and 6 (IL-1beta, IL-6) mediate the acute phase
      response (APR). In liver, they regulate the secretion of acute phase proteins.
      Using RNA-seq in primary hepatocytes, we show that these cytokines regulate
      transcription in a bifurcated manner, leading to both synergistic and
      antagonistic gene expression. By mapping changes in enhancer landscape and
      transcription factor occupancy (using ChIP-seq), we show that synergistic gene
      induction is achieved by assisted loading of STAT3 on chromatin by NF-kappaB.
      With IL-6 treatment alone, STAT3 does not efficiently bind 20% of its coordinated
      binding sites. In the presence of IL-1beta, NF-kappaB is activated, binds a
      subset of enhancers and primes their activity, as evidenced by increasing
      H3K27ac. This facilitates STAT3 binding and synergistic gene expression. Our
      findings reveal an enhancer-specific crosstalk whereby NF-kappaB enables STAT3
      binding at some enhancers while perturbing it at others. This model reconciles
      seemingly contradictory reports of NF-kappaB-STAT3 crosstalk.

PMID- 29185443
TI  - A Feline HFpEF Model with Pulmonary Hypertension and Compromised Pulmonary
      Function.
AB  - Heart Failure with preserved Ejection Fraction (HFpEF) represents a major public
      health problem. The causative mechanisms are multifactorial and there are no
      effective treatments for HFpEF, partially attributable to the lack of well
      established HFpEF animal models. We established a feline HFpEF model induced by
      slow-progressive pressure overload. Male domestic short hair cats (n = 20),
      underwent either sham procedures (n = 8) or aortic constriction (n = 12) with a
      customized pre-shaped band. Pulmonary function, gas exchange, and invasive
      hemodynamics were measured at 4-months post-banding. In banded cats,
      echocardiography at 4-months revealed concentric left ventricular (LV)
      hypertrophy, left atrial (LA) enlargement and dysfunction, and LV diastolic
      dysfunction with preserved systolic function, which subsequently led to elevated
      LV end-diastolic pressures and pulmonary hypertension. Furthermore, LV diastolic
      dysfunction was associated with increased LV fibrosis, cardiomyocyte hypertrophy,
      elevated NT-proBNP plasma levels, fluid and protein loss in pulmonary
      interstitium, impaired lung expansion, and alveolar-capillary membrane
      thickening. We report for the first time in HFpEF perivascular fluid cuff
      formation around extra-alveolar vessels with decreased respiratory compliance.
      Ultimately, these cardiopulmonary abnormalities resulted in impaired oxygenation.
      Our findings support the idea that this model can be used for testing novel
      therapeutic strategies to treat the ever growing HFpEF population.

PMID- 29185445
TI  - Author Correction: Multipurpose silicon photonics signal processor core.
AB  - Change History: A correction to this article has been published and is linked
      from the HTML version of this article.

PMID- 29185444
TI  - Directing intracellular supramolecular assembly with N-heteroaromatic
      quaterthiophene analogues.
AB  - Self-assembly in situ, where synthetic molecules are programmed to organize in a
      specific and complex environment i.e., within living cells, can be a unique
      strategy to influence cellular functions. Here we present a small series of
      rationally designed oligothiophene analogues that specifically target, locate and
      dynamically self-report their supramolecular behavior within the confinement of a
      cell. Through the recognition of the terminal alkyl substituent and the
      amphiphilic pyridine motif, we show that the cell provides different
      complementary pathways for self-assembly that can be traced easily with
      fluorescence microscopy as their molecular organization emits in distinct
      fluorescent bands. Importantly, the control and induction of both forms are
      achieved by time, temperature and the use of the intracellular transport
      inhibitor, bafilomycin A1. We showcase the importance of both intrinsic (cell)
      and extrinsic (stimulus) factors for self-organization and the potential of such
      a platform toward developing synthetic functional components within living cells.

PMID- 29185446
TI  - Penultimate deglacial warming across the Mediterranean Sea revealed by clumped
      isotopes in foraminifera.
AB  - The variability of seawater temperature through time is a critical measure of
      climate change, yet its reconstruction remains problematic in many regions. Mg/Ca
      and oxygen isotope (delta 18OC) measurements in foraminiferal carbonate shells
      can be combined to reconstruct seawater temperature and delta 18O (delta 18OSW).
      The latter is a measure of changes in local hydrology (e.g.,
      precipitation/evaporation, freshwater inputs) and global ice volume. But
      diagenetic processes may affect foraminiferal Mg/Ca. This restricts its potential
      in many places, including the Mediterranean Sea, a strategic region for
      deciphering global climate and sea-level changes. High alkalinity/salinity
      conditions especially bias Mg/Ca temperatures in the eastern Mediterranean
      (eMed). Here we advance the understanding of both western Mediterranean (wMed)
      and eMed hydrographic variability through the penultimate glacial termination
      (TII) and last interglacial, by applying the clumped isotope (Delta 47)
      paleothermometer to planktic foraminifera with a novel data-processing approach.
      Results suggest that North Atlantic cooling during Heinrich stadial 11 (HS11)
      affected surface-water temperatures much more in the wMed (during winter/spring)
      than in the eMed (during summer). The method's paired Delta 47 and delta 18OC
      data also portray delta 18OSW. These records reveal a clear HS11 freshwater
      signal, which attenuated toward the eMed, and also that last interglacial surface
      warming in the eMed was strongly amplified by water-column stratification during
      the deposition of the organic-rich (sapropel) interval known as S5.

PMID- 29185447
TI  - Identification and characterization of genes involving the early step of Juvenile
      Hormone pathway in Helicoverpa armigera.
AB  - Juvenile hormones (JHs) are crucial regulators for multiple physiological
      processes in insects. In the current study, 10 genes in mevalonate pathway
      involved in JH biosynthesis were identified from Helicoverpa armigera. Tissue
      specific expression analysis showed that six genes were highly expressed in the
      head which contained the JH biosynthetic gland (corpora allata). Temporal
      expression pattern showed that 10 of 12 genes were highly transcribed in the late
      2nd-instar when the in vivo JH titer reached the peak, indicating a tight
      correlation between JH titer and the transcription of JH synthetic pathway genes.
      Moreover, ingestion of methoprene, a JH analogue, significantly suppressed the
      transcription of nine JH biosynthetic genes and caused a feedback upregulation of
      the JH degradation enzyme. Particularly, the Acetoacetyl CoA thiolase (HaAce) and
      Farnesyl diphosphate synthase gene 4 (HaFpps4) showed high transcript abundance,
      and their temporal expressions keep pace with JH fluctuations. Further study by
      RNAi showed that knockdown of HaFpps4 caused the decrease of JH titer, led to a
      negative effect on the transcript levels of other genes in JH pathway, and
      resulted in molting disturbance in larvae. Altogether, these results contribute
      to our understanding of JH biosynthesis in H. armigera and provide target genes
      for pest control based on JH-dependent regulation.

PMID- 29185448
TI  - Generation of gene-edited rats by delivery of CRISPR/Cas9 protein and donor DNA
      into intact zygotes using electroporation.
AB  - The generation of gene-edited animals using the CRISPRs/Cas9 system is based on
      microinjection into zygotes which is inefficient, time consuming and demands high
      technical skills. We report the optimization of an electroporation method for
      intact rat zygotes using sgRNAs and Cas9 protein in combination or not with
      ssODNs (~100 nt). This resulted in high frequency of knockouts, between 15 and
      50% of analyzed animals. Importantly, using ssODNs as donor template resulted in
      precise knock-in mutations in 25-100% of analyzed animals, comparable to
      microinjection. Electroporation of long ssDNA or dsDNA donors successfully used
      in microinjection in the past did not allow generation of genome-edited animals
      despite dsDNA visualization within zygotes. Thus, simultaneous electroporation of
      a large number of intact rat zygotes is a rapid, simple, and efficient method for
      the generation of a variety of genome-edited rats.

PMID- 29185449
TI  - Ultrafast and low-energy switching in voltage-controlled elliptical pMTJ.
AB  - Switching magnetization in a perpendicular magnetic tunnel junction (pMTJ) via
      voltage controlled magnetic anisotropy (VCMA) has shown the potential to markedly
      reduce switching energy. However, the requirement of an external magnetic field
      poses a critical bottleneck for its practical applications. In this work, we
      propose an elliptical-shaped pMTJ to eliminate the requirement of providing an
      external field by an additional circuit. We demonstrate that a 10 nm thick in
      plane magnetized bias layer (BL) separated by a metallic spacer of 3 nm from the
      free layer (FL) can be engineered within the MTJ stack to provide the 50 mT bias
      magnetic field for switching. By conducting macrospin simulation, we find that a
      fast switching in 0.38 ns with energy consumption as low as 0.3 fJ at a voltage
      of 1.6 V can be achieved. Furthermore, we study the phase diagram of switching
      probability, showing that a pulse duration margin of 0.15 ns is obtained and low
      voltage operation (~1 V) is favored. Finally, the MTJ scalability is considered,
      and it is found that scaling down may not be appealing in terms of both the
      energy consumption and the switching time for precession based VCMA switching.

PMID- 29185450
TI  - Evaluation of BMMSCs-EPCs sheets for repairing alveolar bone defects in
      ovariectomized rats.
AB  - The aim of this paper is to investigate the effect that bone marrow mesenchymal
      stem cells (BMMSCs) - endothelial progenitor cells (EPCs), BMMSCs and EPCs sheets
      have on repairing maxillary alveolar defects in ovariectomized (OVX) rats. In
      this study, after identification using multi-lineage differentiation and flow
      cytometry, BMMSCs and EPCs were isolated from female rats. The BMMSCs-EPCs,
      BMMSCs and EPCs sheets were detected by hematoxylin-eosin (H&E) staining,
      alkaline phosphatase (ALP) staining and qRT-PCR. Defects were created in
      maxillary alveoli and repaired with BMMSCs-EPCs, BMMSCs and EPCs sheets in OVX
      rats. The repair effects were determined by histological staining and micro-CT
      analysis at 2, 4 and 8 weeks after implantation. We aim to clarify whether BMMSCs
      EPCs sheets are more effective in repairing alveolar bone defects than are BMMSCs
      and EPCs sheets in OVX rats. The results show that the osteogenic potential and
      the effect of bone repair are greater in the BMMSCs-EPCs sheet group and that
      this group has a higher ability to repair alveolar bone defects in OVX rats.
      These results suggest that BMMSCs-EPCs sheets have potential in clinical
      applications for treating humans with osteoporosis.

PMID- 29185451
TI  - Greenhouse gases emissions in rivers of the Tibetan Plateau.
AB  - Greenhouse gases (GHGs) emissions from streams are important to regional
      biogeochemical budgets. This study is one of the first to incorporate stream GHGs
      (CO2, CH4 and N2O) concentrations and emissions in rivers of the Tibetan Plateau.
      With one-time sampling from 32 sites in rivers of the plateau, we found that most
      of the rivers were supersaturated with CO2, CH4 and N2O during the study period.
      Medians of partial pressures of CO2 (pCO2), pCH4 and pN2O were presented 864
      MUatm, 6.3 MUatm, and 0.25 MUatm respectively. Based on a scaling model of the
      flux of gas, the calculated fluxes of CO2, CH4 and N2O (3,452 mg-C m2 d-1, 26.7
      mg-C m2 d-1 and 0.18 mg-N m2 d-1, respectively) in rivers of the Tibetan Plateau
      were found comparable with most other rivers in the world; and it was revealed
      that the evasion rates of CO2 and CH4 in tributaries of the rivers of the plateau
      were higher than those in the mainstream despite its high altitude. Furthermore,
      concentrations of GHGs in the studied rivers were related to dissolved carbon and
      nitrogen, indicating that riverine dissolved components could be used to scale
      GHGs envision in rivers of the Tibetan Plateau.

PMID- 29185452
TI  - DHHC5-mediated palmitoylation of S1P receptor subtype 1 determines G-protein
      coupling.
AB  - Sphingosine 1-phosphate (S1P) is a pleiotropic lipid mediator involved in the
      regulation of immune cell trafficking and vascular permeability acting mainly
      through G-protein-coupled S1P receptors (S1PRs). However, mechanism underlying
      how S1PRs are coupled with G-proteins remains unknown. Here we have uncovered
      that palmitoylation of a prototypical subtype S1P1R is prerequisite for
      subsequent inhibitory G-protein (Gi) coupling. We have identified DHHC5 as an
      enzyme for palmitoylation of S1P1R. Under basal conditions, S1P1R was
      functionally associated with DHHC5 in the plasma membranes (PM) and was fully
      palmitoylated, enabling Gi coupling. Upon stimulation, the receptor underwent
      internalisation leaving DHHC5 in PM, resulting in depalmitoylation of S1P1R. We
      also revealed that while physiological agonist S1P-induced endocytosed S1P1R
      readily recycled back to PM, pharmacological FTY720-P-induced endocytosed S1P1R
      positive vesicles became associated with DHHC5 in the later phase, persistently
      transmitting Gi signals there. This indicates that FTY720-P switches off the S1P
      signal in PM, while switching on its signal continuously inside the cells. We
      propose that DHHC5-mediated palmitoylation of S1P1R determines Gi coupling and
      its signalling in a spatio/temporal manner.

PMID- 29185454
TI  - Graphitizing Non-graphitizable Carbons by Stress-induced Routes.
AB  - Graphitic carbons' unique attributes have attracted worldwide interest towards
      their development and application. Carbon pyrolysis is a widespread method for
      synthesizing carbon materials. However, our understanding of the factors that
      cause differences in graphitization of various pyrolyzed carbon precursors is
      inadequate. We demonstrate how electro-mechanical aspects of the synthesis
      process influence molecular alignment in a polymer precursor to enhance its
      graphitization. Electrohydrodynamic forces are applied via electrospinning to
      unwind and orient the molecular chains of a non-graphitizing carbon precursor,
      polyacrylonitrile. Subsequently, exerting mechanical stresses further enhances
      the molecular alignment of the polymer chains during the formative crosslinking
      phase. The stabilized polymer precursor is then pyrolyzed at 1000  degrees C and
      characterized to evaluate its graphitization. The final carbon exhibits a
      uniformly graphitized structure, abundant in edge planes, which translates into
      its electrochemical kinetics. The results highlight the significance of physical
      synthesis conditions in defining the structure and properties of pyrolytic
      carbons.

PMID- 29185453
TI  - Dysregulation of YAP by ARF Stimulated with Tea-derived Carbon Nanodots.
AB  - YAP is a downstream nuclear transcription factor of Hippo pathway which plays an
      essential role in development, cell growth, organ size and homeostasis. It was
      previously identified that elevation of YAP in genomics of genetic engineered
      mouse (GEM) model of prostate cancer is associated with Pten/Trp53 inactivation
      and ARF elevation hypothesizing the essential crosstalk of AKT/mTOR/YAP with ARF
      in prostate cancer. However, the detailed function and trafficking of YAP in
      cancer cells remains unclear. Using GEM microarray model, we found ARF
      dysregulates Hippo and Wnt pathways. In particular, ARF knockdown reduced non
      nuclear localization of YAP which led to an increase in F-actin. Mechanistically,
      ARF knockdown suppressed protein turnover of beta-catenin/YAP, and therefore
      enhanced the activity of AKT and phosphorylation of YAP. Moreover, we found tea
      derived carbon dots can interact with ARF in nucleus that may further lead to the
      non-nuclear localization of YAP. Thus, we reported a novel crosstalk of ARF/beta
      catenin dysregulated YAP in Hippo pathway and a new approach to stimulate ARF
      mediated signaling to inhibit nuclear YAP using nanomaterials implicating an
      innovative avenue for treatment of cancer.

PMID- 29185455
TI  - Antiphospholipid antibodies increase the levels of mitochondrial DNA in placental
      extracellular vesicles: Alarmin-g for preeclampsia.
AB  - The pathogenesis of preeclampsia remains unclear but placental factors are known
      to play a crucial role causing maternal endothelial cell dysfunction. One
      potential factor is placental micro- and nano- vesicles. Antiphospholipid
      antibodies (aPL) increase the risk of preeclampsia ten-fold, in part by damaging
      the mitochondria in the syncytiotrophoblast. Since mitochondrial DNA (mtDNA) is a
      danger- associated molecular pattern (DAMP/alarmin) that may activate endothelial
      cells, the aims of the current study were to investigate whether aPL affect the
      number of placental vesicles extruded, their mtDNA content and their ability to
      activate endothelial cells. Exposure of first trimester human placental explants
      to aPL affected neither the number nor size of extruded micro- and nano- vesicles
      (n = 5), however their levels of mtDNA were increased (n = 6). These vesicles
      significantly activated endothelial cells (n = 5), which was prevented by
      blocking toll-like receptor 9 (TLR-9), a receptor for extracellular DNA. Thus,
      aPL may increase the risk of preeclampsia in part by increasing the amount of
      mtDNA associated with placental vesicles. That mitochondrial DNA is recognised as
      a DAMP by TLR-9 to cause endothelial cell activation, raises the possibility that
      placental vesicles or TLR-9 might be a target for pharmaceutical intervention to
      reduce the consequences of aPL in pregnancy.

PMID- 29185456
TI  - Tabby graphene: Dimensional magnetic crossover in fluorinated graphite.
AB  - Tabby is a pattern of short irregular stripes, usually related to domestic cats.
      We have produced Tabby patterns on graphene by attaching fluorine atoms running
      as monoatomic chains in crystallographic directions. Separated by non-fluorinated
      sp 2 carbon ribbons, sp 3-hybridized carbon atoms bonded to zigzag fluorine
      chains produce sp 2-sp 3 interfaces and spin-polarized edge states localized on
      both sides of the chains. We have compared two kinds of fluorinated graphite
      samples C2F x , with x near to 1 and x substantially below 1. The magnetic
      susceptibility of C2F x (x < 1) shows a broad maximum and a thermally activated
      spin gap behaviour that can be understood in a two-leg spin ladder model with
      ferromagnetic legs and antiferromagnetic rungs; the spin gap constitutes about
      450 K. Besides, stable room-temperature ferromagnetism is observed in C2F x (x <
      1) samples: the crossover to a three-dimensional magnetic behaviour is due to the
      onset of interlayer interactions. Similarly prepared C2F x (x ~ 1) samples
      demonstrate features of two-dimensional magnetism without signs of high
      temperature magnetic ordering, but with transition to a superparamagnetic state
      below 40 K instead. The magnetism of the Tabby graphene is stable until 520 K,
      which is the temperature of the structural reconstruction of fluorinated
      graphite.

PMID- 29185457
TI  - A first assessment of Fraxinus excelsior (common ash) susceptibility to
      Hymenoscyphus fraxineus (ash dieback) throughout the British Isles.
AB  - Ash dieback (ADB), caused by Hymenoscyphus fraxineus, has severely damaged a
      large proportion of ash trees (Fraxinus excelsior) in continental Europe. We have
      little damage data for the British Isles where the disease was found only five
      years ago in the Southeast, and is still spreading. A large-scale screening trial
      to evaluate ADB damage to provenances of F. excelsior sourced from throughout the
      British Isles was planted in 2013 in the southeast of England. In 2016, we scored
      trees by their level of ADB damage observed in field at the two worst affected
      (based on assessments in 2015) of the 14 sites. Significant differences were
      found in average ADB damage among planting sites and seed source provenances.
      Trees from certain provenances in Scotland were the least damaged by ADB, whereas
      trees from Wales and Southeast England were the most badly damaged in both trial
      sites. Thus the levels of ADB damage currently seen in ash populations in
      Southeast England may not be an accurate predictor of the damage expected in
      future throughout the British Isles. Given all provenances contained some healthy
      trees, a breeding programme to produce genetically variable native ash tree
      populations with lower ADB susceptibility may be feasible.

PMID- 29185458
TI  - Reactive molecular dynamic simulations on the gas separation performance of
      porous graphene membrane.
AB  - The separation of gases molecules with similar diameter and shape is an important
      area of research. For example, the major challenge to set up sweeping carbon
      dioxide capture and storage (CCS) in power plants is the energy requisite to
      separate the CO2 from flue gas. Porous graphene has been proposed as superior
      material for highly selective membranes for gas separation. Here we design some
      models of porous graphene with different sizes and shape as well as employ double
      layers porous graphene for efficient CO2/H2 separation. The selectivity and
      permeability of gas molecules through various nanopores were investigated by
      using the reactive molecular dynamics simulation which considers the bond
      forming/breaking mechanism for all atoms. Furthermore, it uses a geometry
      dependent charge calculation scheme that accounts appropriately for polarization
      effect which can play an important role in interacting systems. It was found that
      H-modified porous graphene membrane with pore diameter (short side) of about 3.75
      A has excellent selectivity for CO2/H2 separation. The mechanism of gas
      penetration through the sub-nanometer pore was presented for the first time. The
      accuracy of MD simulation results validated by valuable DFT method. The present
      findings show that reactive MD simulation can propose an economical means of
      separating gases mixture.

PMID- 29185459
TI  - Analysis and correction of errors in nanoscale particle tracking using the Single
      pixel interior filling function (SPIFF) algorithm.
AB  - Particle tracking, which is an essential tool in many fields of scientific
      research, uses algorithms that retrieve the centroid of tracked particles with
      sub-pixel accuracy. However, images in which the particles occupy a small number
      of pixels on the detector, are in close proximity to other particles or suffer
      from background noise, show a systematic error in which the particle sub-pixel
      positions are biased towards the center of the pixel. This "pixel locking" effect
      greatly reduces particle tracking accuracy. In this report, we demonstrate the
      severity of these errors by tracking experimental (and simulated) imaging data of
      optically trapped silver nanoparticles and single fluorescent proteins. We show
      that errors in interparticle separation, angle and mean square displacement are
      significantly reduced by applying the corrective Single-Pixel Interior Filling
      Function (SPIFF) algorithm. Our work demonstrates the potential ubiquity of such
      errors and the general applicability of SPIFF correction to many experimental
      fields.

PMID- 29185460
TI  - Reprogramming to pluripotency does not require transition through a primitive
      streak-like state.
AB  - Pluripotency can be induced in vitro from adult somatic mammalian cells by
      enforced expression of defined transcription factors regulating and initiating
      the pluripotency network. Despite the substantial advances over the last decade
      to improve the efficiency of direct reprogramming, exact mechanisms underlying
      the conversion into the pluripotent stem cell state are still vaguely understood.
      Several studies suggested that induced pluripotency follows reversed embryonic
      development. For somatic cells of mesodermal and endodermal origin that would
      require the transition through a Primitive streak-like state, which would
      necessarily require an Eomesodermin (Eomes) expressing intermediate. We analyzed
      reprogramming in human and mouse cells of mesodermal as well as ectodermal origin
      by thorough marker gene analyses in combination with genetic reporters,
      conditional loss of function and stable fate-labeling for the broad primitive
      streak marker Eomes. We unambiguously demonstrate that induced pluripotency is
      not dependent on a transient primitive streak-like stage and thus does not
      represent reversal of mesendodermal development in vivo.

PMID- 29185461
TI  - Data driven inference for the repulsive exponent of the Lennard-Jones potential
      in molecular dynamics simulations.
AB  - The Lennard-Jones (LJ) potential is a cornerstone of Molecular Dynamics (MD)
      simulations and among the most widely used computational kernels in science. The
      LJ potential models atomistic attraction and repulsion with century old
      prescribed parameters (q = 6, p = 12, respectively), originally related by a
      factor of two for simplicity of calculations. We propose the inference of the
      repulsion exponent through Hierarchical Bayesian uncertainty quantification We
      use experimental data of the radial distribution function and dimer interaction
      energies from quantum mechanics simulations. We find that the repulsion exponent
      p ~ 6.5 provides an excellent fit for the experimental data of liquid argon, for
      a range of thermodynamic conditions, as well as for saturated argon vapour.
      Calibration using the quantum simulation data did not provide a good fit in these
      cases. However, values p ~ 12.7 obtained by dimer quantum simulations are
      preferred for the argon gas while lower values are promoted by experimental data.
      These results show that the proposed LJ 6-p potential applies to a wider range of
      thermodynamic conditions, than the classical LJ 6-12 potential. We suggest that
      calibration of the repulsive exponent in the LJ potential widens the range of
      applicability and accuracy of MD simulations.

PMID- 29185462
TI  - Histopathological, immunohistochemical, and ultrastructural evidence of
      spontaneous Senecavirus A-induced lesions at the choroid plexus of newborn
      piglets.
AB  - Epidemic Transient Neonatal Losses (ETNL) is a disease of piglets caused by
      Senecavirus A (SVA) in which the method of dissemination and associated lesions
      are not well-defined. This study investigated the possible SVA-induced lesions by
      examining spontaneous infections in newborn piglets. Histopathology revealed
      ballooning degeneration of transitional epithelium, nonsuppurative
      meningoencephalitis, plexus choroiditis, and atrophic enteritis. RT-PCR
      identified SVA in all tissues evaluated and sequencing confirmed these results.
      Positive immunoreactivity to SVA was observed in endothelial and epithelial
      tissues of all organs evaluated. Semithin analysis revealed vacuolization of
      apical enterocytes of the small intestine, balloon degeneration and necrosis of
      endothelial cells of the choroid plexus (CP) and nonsuppurative choroid plexitis.
      Ultrathin evaluation demonstrated hydropic degeneration of apical enterocytes,
      degeneration and necrosis of endothelium of CP fenestrated capillaries,
      degeneration of ependymocytes associated with intralesional viral particles. It
      is proposed that SVA initially infects apical enterocytes of newborn piglets and
      probably enters the circulatory system with entry to the brain via the CP, by
      first producing an initial inflammatory reaction, with subsequent encephalitic
      dissemination. Consequently, SVA probably uses an enteric-neurological method of
      dissemination.

PMID- 29185463
TI  - IL-27, but not IL-35, inhibits neuroinflammation through modulating GM-CSF
      expression.
AB  - IL-27 and IL-35 are heterodimeric cytokines, members of the IL-12 family and
      considered to have immunomodulatory properties. Their role during
      neuroinflammation had been investigated using mutant mice devoid of either one of
      their subunits or lacking components of their receptors, yielding conflicting
      results. We sought to understand the therapeutic potential of IL-27 and IL-35
      delivered by gene therapy in neuroinflammation. We constructed lentiviral vectors
      expressing IL-27 and IL-35 from a single polypeptide chain, and we validated in
      vitro their biological activity. We injected IL-27 and IL-35-expressing
      lentiviral vectors into the cerebrospinal fluid (CSF) of mice affected by
      experimental neuroinflammation (EAE), and performed clinical, neuropathological
      and immunological analyses. Both cytokines interfere with neuroinflammation, but
      only IL-27 significantly modulates disease development, both clinically and
      neuropathologically. IL-27 protects from autoimmune inflammation by inhibiting
      granulocyte macrophages colony-stimulating factor (GM-CSF) expression in CD4+ T
      cells and by inducing program death-ligand 1 (PD-L1) expression in both CNS
      resident and CNS-infiltrating myeloid cells. We demonstrate here that IL-27 holds
      therapeutic potential during neuroinflammation and that IL-27 inhibits GM-CSF and
      induces pd-l1 mRNA in vivo.

PMID- 29185464
TI  - Ripening-induced chemical modifications of papaya pectin inhibit cancer cell
      proliferation.
AB  - Papaya (Carica papaya L.) is a fleshy fruit with a rapid pulp softening during
      ripening. Ripening events are accompanied by gradual depolymerization of pectic
      polysaccharides, including homogalacturonans, rhamnogalacturonans,
      arabinogalactans, and their modified forms. During intermediate phases of papaya
      ripening, partial depolymerization of pectin to small size with decreased
      branching had enhanced pectin anti-cancer properties. These properties were lost
      with continued decomposition at later phases of ripening. Pectin extracted from
      intermediate phases of papaya ripening markedly decreased cell viability, induced
      necroptosis, and delayed culture wound closing in three types of immortalized
      cancer cell lines. The possible explanation for these observations is that papaya
      pectins extracted from the third day after harvesting have disrupted interaction
      between cancer cells and the extracellular matrix proteins, enhancing cell
      detachment and promoting apoptosis/necroptosis. The anticancer activity of papaya
      pectin is dependent on the presence and the branch of arabinogalactan type II
      (AGII) structure. These are first reports of AGII in papaya pulp and the first
      reports of an in vitro biological activity of papaya pectins that were modified
      by natural action of ripening-induced pectinolytic enzymes. Identification of the
      specific pectin branching structures presents a biological route to enhancing
      anti-cancer properties in papaya and other climacteric fruits.

PMID- 29185465
TI  - Probing spatial heterogeneity in silicon thin films by Raman spectroscopy.
AB  - Raman spectroscopy is a powerful technique for revealing spatial heterogeneity in
      solid-state structures but heretofore has not been able to measure spectra from
      multiple positions on a sample within a short time. Here, we report a novel Raman
      spectroscopy approach to study the spatial heterogeneity in thermally annealed
      amorphous silicon (a-Si) thin films. Raman spectroscopy employs both a galvano
      mirror and a two-dimensional charge-coupled device detector system, which can
      measure spectra at 200 nm intervals at every position along a sample in a short
      time. We analyzed thermally annealed a-Si thin films with different film
      thicknesses. The experimental results suggest a correlation between the
      distribution of the average nanocrystal size over different spatial regions and
      the thickness of the thermally annealed a-Si thin film. The ability to evaluate
      the average size of the Si nanocrystals through rapid data acquisition is
      expected to lead to research into new applications of nanocrystals.

PMID- 29185466
TI  - Macropis fulvipes Venom component Macropin Exerts its Antibacterial and Anti
      Biofilm Properties by Damaging the Plasma Membranes of Drug Resistant Bacteria.
AB  - The abuse of antibiotics for disease treatment has led to the emergence of
      multidrug resistant bacteria. Antimicrobial peptides, found naturally in various
      organisms, have received increasing interest as alternatives to conventional
      antibiotics because of their broad spectrum antimicrobial activity and low
      cytotoxicity. In a previous report, Macropin, isolated from bee venom, exhibited
      antimicrobial activity against both gram-positive and negative bacteria. In the
      present study, Macropin was synthesized and its antibacterial and anti-biofilm
      activities were tested against bacterial strains, including gram-positive and
      negative bacteria, and drug resistant bacteria. Moreover, Macropin did not
      exhibit hemolytic activity and cytotoxicity to keratinocytes, whereas Melittin,
      as a positive control, showed very high toxicity. Circular dichroism assays
      showed that Macropin has an alpha-helical structure in membrane mimic
      environments. Macropin binds to peptidoglycan and lipopolysaccharide and kills
      the bacteria by disrupting their membranes. Moreover, the fractional inhibitory
      concentration index indicated that Macropin has additive and partially
      synergistic effects with conventional antibiotics against drug resistant
      bacteria. Thus, our study suggested that Macropin has potential for use of an
      antimicrobial agent for infectious bacteria, including drug resistant bacteria.

PMID- 29185467
TI  - Phylogeography reveals a potential cryptic invasion in the Southern Hemisphere of
      Ceratophyllum demersum, New Zealand's worst invasive macrophyte.
AB  - Ceratophyllum demersum (common hornwort) is presently considered the worst
      invasive submerged aquatic macrophyte in New Zealand. We explored the global
      phylogeographic pattern of the species, based on chloroplast and nuclear DNA, in
      order to identify the origin of the invasive populations in New Zealand and to
      clarify if there were multiple introductions. The phylogeographic study
      identified geographically differentiated gene pools in North America, tropical
      Asia, Australia, and South Africa, likely native to these regions, and a recent
      dispersal event of a Eurasian-related haplotype to North America, New Zealand,
      Australia, and South Africa. At least two different invasive genotypes of this
      Eurasian-related haplotype have been found in New Zealand. One genotype is
      closely related to genotypes in Australia and South Africa, while we could not
      trace the closest relatives of the other genotype within our C. demersum sample
      set. Contrasting spectra of genetic distances in New Zealand and in a region
      within the native range (Denmark), suggest that the invasive population was
      founded by vegetative reproduction, seen as low genetic distances among
      genotypes. We also discovered the introduction of the same Eurasian-related
      haplotype in Australia and South Africa and that a cryptic invasion may be
      occurring in these continents.

PMID- 29185468
TI  - Consistency and flexibility in solving spatial tasks: different horses show
      different cognitive styles.
AB  - Individual animals vary in their behaviour and reactions to novel situations.
      These differences may extend to differences in cognition among individuals. We
      tested twenty-six horses for their ability to detour around symmetric and
      asymmetric obstacles. All of the animals were able to get around the barrier to
      reach a food target, but varied in their approach. Some horses moved slowly but
      were more accurate in choosing the shortest way. Other horses acted quickly,
      consistently detoured in the same direction, and did not reliably choose the
      shortest way. The remaining horses shifted from a faster, directionally
      consistent response with the symmetric barrier, to a slower but more accurate
      response with the asymmetric barrier. The asymmetric barrier induced a reduction
      in heart rate variability, suggesting that this is a more demanding task. The
      different approaches used to solve the asymmetric task may reflect distinct
      cognitive styles in horses, which vary among individuals, and could be linked to
      different personality traits. Understanding equine behaviour and cognition can
      inform horse welfare and management.

PMID- 29185469
TI  - Transformation of Organostannanes Based on Photocleavage of C-Sn Bond via Single
      Electron Transfer Process.
AB  - In this work, we developed a new method for the transformation of organostannanes
      via radical process. In this reaction, highly reactive carbon radical species can
      be efficiently generated through HBr-catalyzed photocleavage of C-Sn bond via
      single electron transfer process. Under aerobic conditions, the in situ formed
      primary/secondary alkyl radicals can be further highly selectively oxidized into
      carboxylic acids/ketones, respectively.

PMID- 29185470
TI  - All-dielectric polarization-independent optical angular filter.
AB  - We report on an all-dielectric, polarization-independent angular filter with one
      dimension (1D) photonic crystal (PC) composed of semiconductor compatible Si/SiO2
      pairs. The near-symmetric directional band gap of p- and s-polarized components
      and Fabry-Perot (F-P) resonances are utilized to realize efficient polarization
      independent angular filtering for normal incidence. The proposed angular filter
      is designed and experimentally demonstrated in a large area (5 cm * 5 cm) with
      multilayer sputtering depositions. Experimental measurements show that a
      divergence angle of the polarization-independently transmitted beam through the
      angular filtering sample at 1550 nm is 2.2 degrees  only and the transmission is
      as high as 0.8 at normal incidence. The proposed and demonstrated angular filter
      suggests an effective way to design and implement semiconductor compatible, all
      dielectric and polarization-independent angular filters in a fashion of simple
      structure and easy-fabrication, which is expected to have great applications in
      lighting, beam manipulation, optical coupling and optical communications.

PMID- 29185471
TI  - Capsize of polarization in dilute photonic crystals.
AB  - We investigate, experimentally and theoretically, polarization rotation effects
      in dilute photonic crystals with transverse permittivity inhomogeneity
      perpendicular to the traveling direction of waves. A capsize, namely a drastic
      change of polarization to the perpendicular direction is observed in a one
      dimensional photonic crystal in the frequency range 10 / 140 GHz. To gain more
      insights into the rotational mechanism, we have developed a theoretical model of
      dilute photonic crystal, based on Maxwell's equations with a spatially dependent
      two dimensional inhomogeneous dielectric permittivity. We show that the
      polarization's rotation can be explained by an optical splitting parameter
      appearing naturally in Maxwell's equations for magnetic or electric fields
      components. This parameter is an optical analogous of Rashba like spin-orbit
      interaction parameter present in quantum waves, introduces a correction to the
      band structure of the two-dimensional Bloch states, creates the dynamical phase
      shift between the waves propagating in the orthogonal directions and finally
      leads to capsizing of the initial polarization. Excellent agreement between
      theory and experiment is found.

PMID- 29185472
TI  - Computational and NMR spectroscopy insights into the conformation of cyclic di
      nucleotides.
AB  - Cyclic di-nucleotides (CDNs) are second messengers in bacteria and metazoan that
      are as such controlling important biological processes. Here the conformational
      space of CDNs was explored systematically by a combination of extensive
      conformational search and DFT calculations as well as NMR methods. We found that
      CDNs adopt pre-organized conformations in solution in which the ribose
      conformations are North type and glycosidic bond conformations are anti type. The
      overall flexibility of CDNs as well as the backbone torsion angles depend on the
      cyclization of the phosphodiester bond. Compared to di-nucleotides, CDNs display
      high rigidity in the macrocyclic moieties. Structural comparison studies
      demonstrate that the pre-organized conformations of CDNs highly resemble the
      biologically active conformations. These findings provide information for the
      design of small molecules to modulate CDNs signalling pathways in bacteria or as
      vaccine adjuvants. The rigidity of the backbone of CDNs enables the design of
      high order structures such as molecular cages based on CDNs analogues.

PMID- 29185473
TI  - The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7
      Stimulation as Imiquimod Enters the Circulation.
AB  - Topical application of Aldara cream, containing the Toll-like receptor 7/8
      agonist Imiquimod, is a widely used mouse model for investigating the
      pathogenesis of psoriasis. We have previously used this model to study the
      effects of peripheral inflammation on the brain, and reported a brain-specific
      response characterised by increased transcription, infiltration of immune cells
      and anhedonic-like behavior. Here, we perform a more robust characterisation of
      the systemic response to Aldara application and find a potent but transient
      response in the periphery, followed by a prolonged response in the brain. Mass
      spectrometry analysis of plasma and brain samples identified significant levels
      of Imiquimod in both compartments at molar concentrations likely to evoke a
      biological response. Indeed, the association of Imiquimod with the brain
      correlated with increased Iba1 and GFAP staining, indicative of microglia and
      astrocyte reactivity. These results highlight the potency of this model and raise
      the question of how useful it is for interpreting the systemic response in
      psoriasis-like skin inflammation. In addition, the potential impact on the brain
      should be considered with regards to human use and may explain why fatigue,
      headaches and nervousness have been reported as side effects following prolonged
      Aldara use.

PMID- 29185474
TI  - Exploration of Hand Grasp Patterns Elicitable Through Non-Invasive Proximal Nerve
      Stimulation.
AB  - Various neurological conditions, such as stroke or spinal cord injury, result in
      an impaired control of the hand. One method of restoring this impairment is
      through functional electrical stimulation (FES). However, traditional FES
      techniques often lead to quick fatigue and unnatural ballistic movements. In this
      study, we sought to explore the capabilities of a non-invasive proximal nerve
      stimulation technique in eliciting various hand grasp patterns. The ulnar and
      median nerves proximal to the elbow joint were activated transcutanously using a
      programmable stimulator, and the resultant finger flexion joint angles were
      recorded using a motion capture system. The individual finger motions averaged
      across the three joints were analyzed using a cluster analysis, in order to
      classify the different hand grasp patterns. With low current intensity (<5 mA and
      100 us pulse width) stimulation, our results show that all of our subjects
      demonstrated a variety of consistent hand grasp patterns including single finger
      movement and coordinated multi-finger movements. This study provides initial
      evidence on the feasibility of a proximal nerve stimulation technique in
      controlling a variety of finger movements and grasp patterns. Our approach could
      also be developed into a rehabilitative/assistive tool that can result in
      flexible movements of the fingers.

PMID- 29185475
TI  - Transcriptome Analysis of Two Species of Jute in Response to Polyethylene Glycol
      (PEG)- induced Drought Stress.
AB  - Drought stress results in significant crop yield losses. Comparative
      transcriptome analysis between tolerant and sensitive species can provide
      insights into drought tolerance mechanisms in jute. We present a comprehensive
      study on drought tolerance in two jute species-a drought tolerant species
      (Corchorus olitorius L., GF) and a drought sensitive species (Corchorus
      capsularis L., YY). In total, 45,831 non-redundant unigenes with average sequence
      length of 1421 bp were identified. Higher numbers of differentially expressed
      genes (DEGs) were discovered in YY (794) than in GF (39), implying that YY was
      relatively more vulnerable or hyper-responsive to drought stress at the molecular
      level; the two main pathways, phenylpropanoid biosynthesis and peroxisome
      pathway, significantly involved in scavenging of reactive oxygen species (ROS)
      and 14 unigenes in the two pathways presented a significant differential
      expression in response to increase of superoxide. Our classification analysis
      showed that 1769 transcription factors can be grouped into 81 families and 948
      protein kinases (PKs) into 122 families. In YY, we identified 34 TF DEGs from and
      23 PK DEGs, including 19 receptor-like kinases (RLKs). Most of these RLKs were
      downregulated during drought stress, implying their role as negative regulators
      of the drought tolerance mechanism in jute.

PMID- 29185476
TI  - Fine platinum nanoparticles supported on a porous ceramic membrane as efficient
      catalysts for the removal of benzene.
AB  - It would be desirable to remove volatile organic compounds (VOCs) while we
      eliminate the dusts using silicon carbide (SiC)-based porous ceramics from the
      hot gases. Aiming at functionalizing SiC-based porous ceramics with catalytic
      capability, we herein report a facile strategy to integrate high efficient
      catalysts into the porous SiC substrates for the VOC removal. We demonstrate an
      aqueous salt method for uniformly distributing fine platinum (Pt) particles on
      the alumina (Al2O3) layers, which are pre-coated on the SiC substrates as
      supports for VOC catalysts. We confirm that at a Pt mass loading as low as 0.176%
      and a weight hourly space velocity of 6000 mL g-1 h-1, the as-prepared
      Pt/SiC@Al2O3 catalysts can convert 90% benzene at a temperature of ca. 215 
      degrees C. The results suggest a promising way to design ceramics-based bi
      functional materials for simultaneously eliminating dusts and harmful VOCs from
      various hot gases.

PMID- 29185477
TI  - Single shot laser writing with sub-nanosecond and nanosecond bursts of
      femtosecond pulses.
AB  - A method is proposed for efficient laser modification of fused silica and
      sapphire by means of a burst of femtosecond pulses having time separation in the
      range 10-3000 ps. Modification enhancement with the pulse separation increase in
      the burst was observed on the tens picoseconds scale. It is proposed that
      accumulated transient tensile strain in the excitation region plays a crucial
      role in modification by a sub-nanosecond burst.

PMID- 29185478
TI  - Charge-state Resolved Infrared Multiple Photon Dissociation (IRMPD) Spectroscopy
      of Ubiquitin Ions in the Gas Phase.
AB  - In this study, we obtained for the first time the direct infrared multiple photon
      dissociation (IRMPD) spectra of ubiquitin ions in the range 2700-3750 cm-1.
      Ubiquitin ions with different charge states showed absorption in the two regions
      of 2940-3000 cm-1 and 3280-3400 cm-1. The increase of the charge state of
      ubiquitin ions broadened the absorption peak on the high-frequency side in the
      second region, indicating some hydrogen bonds were weakened due to Coulomb
      interaction. It is also found that the relative intensity of the absorption peak
      in the first region compared to the absorption peak in the second region
      increased with increasing charge state, making the IRMPD spectra charge-state
      resolved. Although it is usually reasonable to suggest the origin of the
      absorption in the range 2940-3000 cm-1 as the C-H bond stretching modes, the
      results show significantly reduced absorption after the deuteration of all labile
      hydrogen atoms. A possible explanation for this is that the coupling coefficients
      between the C-H vibrational mode and other selective modes decreased greatly
      after the deuteration, reducing the rate of energy redistribution and probability
      of consecutive IR absorption.

PMID- 29185479
TI  - Characterising Pre-pubertal Resistance to Death from Endotoxemia.
AB  - Sepsis is a common and deadly syndrome in which a dysregulated host response to
      infection causes organ failure and death. The current lack of treatment options
      suggests that a new approach to studying sepsis is needed. Pre-pubertal children
      show a relative resistance to death from severe infections and sepsis. To explore
      this phenomenon experimentally, we used an endotoxemia model of sepsis in mice.
      Following intra-peritoneal injection of endotoxin, pre-pubertal mice showed
      greater survival than post-pubertal mice (76.3% vs. 28.6%), despite exhibiting a
      similar degree of inflammation after two hours. Age-associated differences in the
      inflammatory response only became evident at twenty hours, when post-pubertal
      mice showed prolonged elevation of serum cytokines and differential recruitment
      of peritoneal immune cells. Mechanistically, prevention of puberty by hormonal
      blockade or acceleration of puberty by oestrogen treatment led to increased or
      decreased survival from endotoxemia, respectively. Additionally, the adoptive
      transfer of pre-pubertal peritoneal cells improved the survival of post-pubertal
      recipient mice, while post-pubertal peritoneal cells or vehicle did not. These
      data establish a model for studying childhood resistance to mortality from
      endotoxemia, demonstrate that oestrogen is responsible for an increased
      susceptibility to mortality after puberty, and identify peritoneal cells as
      mediators of pre-pubertal resistance.

PMID- 29185480
TI  - Initial Cross-Over Test of A Positive Allosteric Modulator of Alpha-7 Nicotinic
      Receptors to Aid Cessation in Smokers With Or Without Schizophrenia.
AB  - Preclinical research shows that compounds acting at alpha7 nicotinic receptors
      (nAChRs) can reduce nicotine self-administration, suggesting that a positive
      allosteric modulator (PAM) of alpha7 receptors, JNJ-39393406, may aid smoking
      cessation. Moreover, individuals with schizophrenia, who have very high rates of
      smoking, have reduced expression of alpha7 nAChRs and may particularly benefit
      from this compound. In two parallel studies using a within-subject cross-over
      design, 36 healthy smokers (Study 1) and 62 smokers with schizophrenia (Study 2),
      both groups high in quit interest, attempted to initiate quitting temporarily
      during each of two 3-week phases. Treatments were the alpha7 nicotinic receptor
      PAM JNJ-39393406 (100 mg b.i.d.) or placebo (double-blind, counter-balanced). In
      each phase, all smoked ad lib with no drug on week 1 or during dose run-up on
      week 2, and then tried to quit every day during week 3. Abstinence (confirmed by
      CO <5 p.p.m.) and smoking reduction (CO <8), as well as cigarettes/day (in Study
      1), were assessed daily (Monday-Friday) each quit week and compared between
      conditions. Secondary outcomes included abstinence symptoms (withdrawal and
      craving) and cognitive test responding (N-back; continuous performance task). In
      both studies, compared with placebo, active JNJ-39393406 did not increase the
      number of abstinent days nor reduce total smoking exposure. We also found no
      significant improvements in craving, withdrawal, or cognitive function. With this
      dose and study duration, our findings do not support further testing of this
      alpha7 nAChR PAM compound for possible efficacy in smoking cessation, in smokers
      with or without schizophrenia.

PMID- 29185481
TI  - Methamphetamine Induces Dopamine Release in the Nucleus Accumbens Through a Sigma
      Receptor-Mediated Pathway.
AB  - Methamphetamine (METH) is a drug with a high addictive potential that is widely
      abused across the world. Although it is known that METH dysregulates both
      dopamine transmission and dopamine reuptake, the specific mechanism of action
      remains obscure. One promising target of METH is the sigma receptor, a chaperone
      protein located on the membrane of the endoplasmic reticulum. Using fast-scan
      cyclic voltammetry, we show that METH-enhancement of evoked dopamine release and
      basal efflux is dependent on sigma receptor activation. METH-induced activation
      of sigma receptors results in oxidation of a cysteine residue on VMAT2, which
      decreases transporter function. Unilateral injections of the sigma receptor
      antagonist BD-1063 prior to METH administration increased dopamine-related
      ipsilateral circling behavior, indicating the involvement of sigma receptors.
      These findings suggest that interactions between METH and the sigma receptor lead
      to oxidative species (most likely superoxide) that in turn oxidize VMAT2.
      Altogether, these findings show that the sigma receptor has a key role in METH
      dysregulation of dopamine release and dopamine-related behaviors.

PMID- 29185482
TI  - A novel role for OATP2A1/SLCO2A1 in a murine model of colon cancer.
AB  - Prostaglandin E2 (PGE2) is associated with proliferation and angiogenesis in
      colorectal tumours. The role of prostaglandin transporter OATP2A1/SLCO2A1 in
      colon cancer tumorogenesis is unknown. We evaluated mice of various Slco2a1
      genotypes in a murine model of colon cancer, the adenomatous polyposis (APC)
      mutant (Apc ?716/+) model. Median lifespan was significantly extended from 19
      weeks in Slco2a1 +/+/Apc Delta716/+ mice to 25 weeks in Slco2a1 -/-/Apc
      Delta716/+ mice. Survival was directly related to a reduction in the number of
      large polyps in the Slco2a1 -/- /Apc ?716/+ compared to the Slco2a1 +/+/Apc
      Delta716/+ or Slco2a1 +/-/Apc Delta716/+mice. The large polyps from the Slco2a1 
      /- /Apc ?716/+ mice had significant reductions in microvascular density,
      consistent with the high expression of Slco2a1 in the tumour-associated vascular
      endothelial cells. Chemical suppression of OATP2A1 function significantly reduced
      tube formation and wound-healing activity of PGE2 in human vascular endothelial
      cells (HUVECs) although the amount of extracellular PGE2 was not affected by an
      OATP2A1 inhibitor. Further an in vivo model of angiogenesis, showed a significant
      reduction of haemoglobin content (54.2%) in sponges implanted into Slco2a1 -/-,
      compared to wildtype mice. These studies indicate that OATP2A1 is likely to
      promote tumorogenesis by PGE2 uptake into the endothelial cells, suggesting that
      blockade of OATP2A1 is an additional pharmacologic strategy to improve colon
      cancer outcomes.

PMID- 29185483
TI  - Impact of Mismatch Angle on Electronic Transport Across Grain Boundaries and
      Interfaces in 2D Materials.
AB  - We study the impact of grain boundaries (GB) and misorientation angles between
      grains on electronic transport in 2-dimensional materials. Here we have developed
      a numerical model based on the first-principles electronic bandstructure
      calculations in conjunction with a method which computes electron transmission
      coefficients from simultaneous conservation of energy and momentum at the
      interface to essentially evaluate GB/interface resistance in a Landauer
      formalism. We find that the resistance across graphene GBs vary over a wide range
      depending on misorientation angles and type of GBs, starting from 53 Omega MUm
      for low-mismatch angles in twin (symmetric) GBs to about 1020 Omega MUm for 21
      degrees  mismatch in tilt (asymmetric) GBs. On the other hand, misorientation
      angles have weak influence on the resistance across MoS2 GBs, ranging from about
      130 Omega MUm for low mismatch angles to about 6000 Omega MUm for 21 degrees .
      The interface resistance across graphene-MoS2 heterojunctions also exhibits a
      strong dependence on misorientation angles with resistance values ranging from
      about 100 Omega MUm for low-mismatch angles in Class-I (symmetric) interfaces to
      1015 Omega MUm for 14 degrees  mismatch in Class-II (asymmetric) interfaces.
      Overall, symmetric homo/heterojunctions exhibit a weak dependence on
      misorientation angles, while in MoS2 both symmetric and asymmetric GBs show a
      gradual dependence on mismatch angles.

PMID- 29185484
TI  - Memory effect behavior with respect to the crystal grain size in the organic
      inorganic hybrid perovskite nonvolatile resistive random access memory.
AB  - The crystal grain size of CH3NH3PbI3 (MAPbI3) organic-inorganic hybrid perovskite
      (OHP) film was controllable in the range from ~60 nm to ~600 nm by non-solvents
      inter-diffusion controlled crystallization process in dripping crystallization
      method for the formation of perovskite film. The MAPbI3 OHP non-volatile
      resistive random access memory with ~60 nm crystal grain size exhibited >0.1
      TB/in2 storage capacity, >600 cycles endurance, >104 s data retention time, ~0.7
      V set, and ~-0.61 V re-set bias voltage.

PMID- 29185485
TI  - Strong localization of oxidized Co3+ state in cobalt-hexacyanoferrate.
AB  - Secondary batteries are important energy storage devices for a mobile equipment,
      an electric car, and a large-scale energy storage. Nevertheless, variation of the
      local electronic state of the battery materials in the charge (or oxidization)
      process are still unclear. Here, we investigated the local electronic state of
      cobalt-hexacyanoferrate (Na x Co[Fe(CN)6]0.9), by means of resonant inelastic X
      ray scattering (RIXS) with high energy resolution (~100 meV). The L-edge RIXS is
      one of the most powerful spectroscopic technique with element- and valence
      selectivity. We found that the local electronic state around Co2+ in the
      partially-charged Na1.1Co2+0.5Co3+0.5[Fe2+(CN)6]0.9 film (x = 1.1) is the same as
      that of the discharged Na1.6Co2+[Fe2+(CN)6]0.9 film (x = 1.6) within the energy
      resolution, indicating that the local electronic state around Co2+ is invariant
      against the partial oxidization. In addition, the local electronic state around
      the oxidized Co3+ is essentially the same as that of the fully-charged film
      Co3+[Fe2+(CN)6]0.3[Fe3+(CN)6]0.6 (x = 0.0) film. Such a strong localization of
      the oxidized Co3+ state is advantageous for the reversibility of the redox
      process, since the localization reduces extra reaction within the materials and
      resultant deterioration.

PMID- 29185486
TI  - Metabolomics profiling reveals different patterns in an animal model of asphyxial
      and dysrhythmic cardiac arrest.
AB  - Cardiac arrest (CA) is not a uniform condition and its pathophysiology strongly
      depends on its cause. In this work we have used a metabolomics approach to study
      the dynamic metabolic changes occurring in the plasma samples of a swine model
      following two different causes of CA, namely asphyxia (ACA) and ventricular
      fibrillation (VFCA). Plasma samples were collected at baseline and every minute
      during the experimental phases. In order to identify the metabolomics profiles
      characterizing the two pathological entities, all samples were analysed by 1H NMR
      spectroscopy and LC-MS/MS spectrometry.The metabolomics fingerprints of ACA and
      VFCA significantly differed during the peri-arrest period and the resuscitation
      phase. Major alterations were observed in plasma concentrations of metabolites
      related to tricarboxylic acid (TCA) cycle, urea cycle, and anaplerotic
      replenishing of TCA. ACA animals showed significant metabolic disturbances during
      the asphyxial and CA phases, while for VFCA animals this phenomenon resulted
      shifted at the resuscitation phase. Interestingly, starting from the asphyxial
      phase, the ACA animals were stratified in two groups based on their metabolomics
      profiles that resulted to be correlated with the clinical outcome. Succinate
      overproduction was observed in the animals with the worse outcome, suggesting a
      potential prognostic role for this metabolite.

PMID- 29185487
TI  - Cross-reactivity of antibodies against interferon beta in multiple sclerosis
      patients and interference of the JAK-STAT signaling pathway.
AB  - Interferon beta (IFNbeta) therapy has immunogenic properties and induces the
      development of neutralizing antibodies (NAbs). From the extensive literature
      focused in the development of NAbs in multiple sclerosis (MS) patients, their
      ability to cross-react has been deficiently evaluated, despite having important
      consequences in the clinical practice. Here, the relation between the cross
      reactivity and the NAbs titers has been evaluated in MS patients, by inhibition
      of the antiviral activity of IFNbeta by bioassay and through the interference
      with the activation of the IFNbeta pathway (JAK-STAT), by phosphoflow. Thus,
      patients with intermediate-high titers of NAbs, determined by bioassay, had a 79
      fold increased risk of cross-reactivity compared to patients with low titers. The
      cross-reactivity is also demonstrated because NAbs positive sera were able to
      decrease significantly the activation of pSTAT1 achieved by other different
      IFNbeta molecules in the cells patients. Besides, a linear relationship between
      the STAT1 phosphorylation and NAbs titers was found. The study demonstrates that
      cross-reactivity increases with the titer of antibodies, which has important
      implications in clinical practice when switching the treatment. The direct
      relationship between the NAbs titer and the activation of STAT1 suggest that its
      determination could be an indirect method to identify the presence of NAbs.

PMID- 29185488
TI  - MicroRNA regulation of Transthyretin in trophoblast differentiation and Intra
      Uterine Growth Restriction.
AB  - Placental trophoblast cells produce various cytokines, transporters vital to
      normal embryogenesis. Transthyretin (TTR) aids trans-placental passage of
      maternal thyroxin (TH) to fetal circulation. Inadequate TH delivery leads to
      developmental abnormality. Regulation of TTR biosynthesis in placenta is critical
      for normal embryo development. We showed here that TTR transcripts were expressed
      more in fetal placenta. Using bioinformatic analysis and confirmation with dual
      luciferase reporter assays, we found that miR-200a-3p and miR-141-3p inhibited
      TTR expression by directly binding to the 3'UTR of TTR, which is reversed by
      mutation in the microRNA binding site. Differentiation of human trophoblast BeWo
      cells was associated with decreased TTR transcript and protein levels with
      concomitant increase in the levels of both microRNAs. Interestingly, ectopic
      overexpression of the microRNA mimics abrogated thyroxin uptake by BeWo cells,
      which was reversed by the corresponding inhibitors. Furthermore, in a rat model
      of intra-uterine growth restriction (IUGR), TTR expression decreased
      significantly in placenta with reciprocal rise in miR-141-3p but not 200a-3p. In
      human IUGR placenta, TTR transcript and protein levels were significantly lower
      associated with high expression of miR-141-3p but not 200a-3p. These data
      provides new insight into physiological role of miR-141-3p in regulating TTR
      during trophoblast differentiation and IUGR.

PMID- 29185489
TI  - Risk of mortality during and after the 2011 Great East Japan Earthquake and
      Tsunami among older coastal residents.
AB  - The Japan Gerontological Evaluation Study is a nationwide cohort study of
      individuals aged 65 years and older established in July 2010. Seven months later,
      one of the study field sites was directly in the line of the 2011 Great East
      Japan Earthquake and Tsunami. Despite the 1-hour warning interval between the
      earthquake and tsunami, many coastal residents lost their lives. We analyzed the
      risk of all-cause mortality on the day of the disaster as well as in the 38-month
      interval after the disaster. Among 860 participants, 33 (3.8%) died directly
      because of the tsunami and an additional 95 people died during the 38-month
      follow-up period. Individuals with depressive symptoms had elevated risk of
      mortality on the day of the disaster (odds ratio = 3.90 [95% CI: 1.13, 13.47]).
      More socially connected people also suffered increased risk of mortality,
      although these estimates were not statistically significant. In contrast, after
      the disaster, frequent social interactions reverted back to predicting improved
      survival (hazard ratio = 0.46 (95% CI: 0.26, 0.82)). Depressive symptoms and
      stronger social connectedness were associated with increased risk of mortality on
      the day of the disaster. After the disaster, social interactions were linked to
      improved survival.

PMID- 29185491
TI  - Observability of Complex Systems: Finding the Gap.
AB  - For a reconstruction of state and parameter values in a dynamic system model,
      first the question whether these values can be uniquely determined from the data
      must be answered. This structural model property is known as observability or, in
      case of parameter calibration only, identifiability. Testing a given model for
      observability is a well studied problem in the systems and control sciences.
      However, it is increasingly difficult, if not impossible, to address this
      property for large size models that, nowadays, are frequently used. We
      demonstrate the application of a recently developed algorithm that overcomes this
      problem and is remarkably efficient. As an illustration we show how an
      observability analysis for a Chinese Hamster Ovary Cell model (34 states, 117
      parameters), a JAKSTAT signalling model (31 states, 51 parameters), and a MAP
      Kinase model (100 states, 88 parameters) can be established in a very short time.

PMID- 29185490
TI  - Aberrant brain response after auditory deviance in PTSD compared to trauma
      controls: An EEG study.
AB  - Part of the symptomatology of post-traumatic stress disorder (PTSD) are
      alterations in arousal and reactivity which could be related to a maladaptive
      increase in the automated sensory change detection system of the brain. In the
      current EEG study we investigated whether the brain's response to a simple
      auditory sensory change was altered in patients with PTSD relative to trauma
      exposed matched controls who did not develop the disorder. Thirteen male PTSD
      patients and trauma-exposed controls matched for age and educational level were
      presented with regular auditory pure tones (1000 Hz, 200 ms duration), with 11%
      of the tones deviating in both duration (50 ms) and frequency (1200 Hz) while
      watching a silent movie. Relative to the controls, patients who had developed
      PTSD showed enhanced mismatch negativity (MMN), increased theta power (5-7 Hz),
      and stronger suppression of upper alpha activity (13-15 Hz) after deviant vs.
      standard tones. Behaviourally, the alpha suppression in PTSD correlated with
      decreased spatial working memory performance suggesting it might reflect enhanced
      stimulus-feature representations in auditory memory. These results taken together
      suggest that PTSD patients and trauma-exposed controls can be distinguished by
      enhanced involuntary attention to changes in sensory patterns.

PMID- 29185492
TI  - Interaction profiling of RNA-binding ubiquitin ligases reveals a link between
      posttranscriptional regulation and the ubiquitin system.
AB  - RNA-binding ubiquitin ligases (RBULs) have the potential to link RNA-mediated
      mechanisms to protein ubiquitylation. Despite this, the cellular functions,
      substrates and interaction partners of most RBULs remain poorly characterized.
      Affinity purification (AP) combined with quantitative mass spectrometry (MS)
      based proteomics is a powerful approach for analyzing protein functions. Mapping
      the physiological interaction partners of RNA-binding proteins has been hampered
      by their intrinsic properties, in particular the existence of low-complexity
      regions, which are prone to engage in non-physiological interactions. Here, we
      used an adapted AP approach to identify the interaction partners of human RBULs
      harboring different RNA-binding domains. To increase the likelihood of recovering
      physiological interactions, we combined control and bait-expressing cells prior
      to lysis. In this setup, only stable interactions that were originally present in
      the cell will be identified. We exploit gene function similarity between the bait
      proteins and their interactors to benchmark our approach in its ability to
      recover physiological interactions. We reveal that RBULs engage in stable
      interactions with RNA-binding proteins involved in different steps of RNA
      metabolism as well as with components of the ubiquitin conjugation machinery and
      ubiquitin-binding proteins. Our results thus demonstrate their capacity to link
      posttranscriptional regulation with the ubiquitin system.

PMID- 29185493
TI  - On-chip integrated vertically aligned carbon nanotube based super- and
      pseudocapacitors.
AB  - On-chip energy storage and management will have transformative impacts in
      developing advanced electronic platforms with built-in energy needs for operation
      of integrated circuits driving a microprocessor. Though success in growing stand
      alone energy storage elements such as electrochemical capacitors (super and
      pseusocapacitors) on a variety of substrates is a promising step towards this
      direction. In this work, on-chip energy storage is demonstrated using
      architectures of highly aligned vertical carbon nanotubes (CNTs) acting as
      supercapacitors, capable of providing large device capacitances. The efficiency
      of these structures is further increased by incorporating electrochemically
      active nanoparticles such as MnOx to form pseudocapacitive architectures thus
      enhancing device capacitance areal specific capacitance of 37 mF/cm2. The
      demonstrated on-chip integration is up and down-scalable, compatible with
      standard CMOS processes, and offers lightweight energy storage what is vital for
      portable and autonomous device operation with numerous advantages as compared to
      electronics built from discrete components.

PMID- 29185494
TI  - Performance enhancement of a brain-computer interface using high-density multi
      distance NIRS.
AB  - This study investigated the effectiveness of using a high-density multi-distance
      source-detector (SD) separations in near-infrared spectroscopy (NIRS), for
      enhancing the performance of a functional NIRS (fNIRS)-based brain-computer
      interface (BCI). The NIRS system that was used for the experiment was capable of
      measuring signals from four SD separations: 15, 21.2, 30, and 33.5 mm, and this
      allowed the measurement of hemodynamic response alterations at various depths.
      Fifteen participants were asked to perform mental arithmetic and word chain
      tasks, to induce task-related hemodynamic response variations, or they were asked
      to stay relaxed to acquire a baseline signal. To evaluate the degree of BCI
      performance enhancement by high-density channel configuration, the classification
      accuracy obtained using a typical low-density lattice SD arrangement, was
      compared to that obtained using the high-density SD arrangement, while
      maintaining the SD separation at 30 mm. The analysis results demonstrated that
      the use of a high-density channel configuration did not result in a noticeable
      enhancement of classification accuracy. However, the combination of hemodynamic
      variations, measured by two multi-distance SD separations, resulted in the
      significant enhancement of overall classification accuracy. The results of this
      study indicated that the use of high-density multi-distance SD separations can
      likely provide a new method for enhancing the performance of an fNIRS-BCI.

PMID- 29185495
TI  - Impact of customary fluoride rinsing solutions on the pellicle's protective
      properties and bioadhesion in situ.
AB  - This study investigated the impact of customary fluoride based mouthrinses on the
      ultrastructure and the functional properties of the in situ pellicle, considering
      the prevention of erosion (8 volunteers) and initial biofilm formation (12
      volunteers). Bovine enamel slabs were carried intraorally. After 1 min of
      pellicle formation, the subjects rinsed with elmex Kariesschutz (A), Dontodent
      Med Care (B), meridol (C) or elmex Zahnschmelzschutz Professional (D) for 1 min.
      In situ pellicle formation was continued up to 30 min/8 h before processing the
      slabs in vitro. Erosion was simulated by incubating the specimens in HCl (pH 3.0,
      2.3, 2.0) for 120 s, measuring the kinetics of calcium/phosphate release
      photometrically; representative samples were evaluated by TEM and EDX. Bacterial
      adhesion was visualized fluorescence microscopically (DAPI/BacLight). Native
      enamel slabs or physiological pellicle samples served as controls. All
      investigated mouthrinses enhanced the erosion preventive pellicle effect in
      dependence of the pH-value. A significant decrease of Ca/P release at all pH
      values was achieved after rinsing with D; TEM/EDX confirmed ultrastructural
      pellicle modifications. All mouthrinses tendentially reduced bacterial adherence,
      however not significantly. The mouthrinse containing NaF/AmF/SnCl2 (D) offers an
      effective oral hygiene supplement to prevent caries and erosion.

PMID- 29185497
TI  - High throughput deep sequencing reveals the important roles of microRNAs during
      sweetpotato storage at chilling temperature.
AB  - Sweetpotato (Impomoea batatas L.) is a globally important economic food crop with
      a potential of becoming a bioenergy and pharmaceutical crop. Thus, studying the
      molecular mechanism of tuberous root development and storage is very important.
      However, not too much progress has been made in this field. In this study, we
      employed the next generation high-throughput deep sequencing technology to
      sequence all small RNAs and degradome of sweetpotato for systematically
      investigating sweetpotato response to chilling stress during storage. A total of
      190 known microRNAs (miRNAs) and 191 novel miRNAs were identified, and 428
      transcripts were targeted by 184 identified miRNAs. More importantly, we
      identified 26 miRNAs differentially expressed between chilling stress and control
      conditions. The expression of these miRNAs and their targets was also confirmed
      by qRT-PCR. Integrated analysis of small RNAs and degradome sequencing reveals
      that miRNA-mediated SA signaling, ABA-dependent, and ROS response pathways are
      involved in sweetpotato root response to chilling stress during storage.

PMID- 29185496
TI  - The effect of primary total knee arthroplasty on the incidence of falls and
      balance-related functions in patients with osteoarthritis.
AB  - Knee osteoarthritis (OA) is an established risk factor for falls and balance
      impairment. This study investigated the incidence of falls, balance-related
      outcomes and risk factors for falls before and after primary total knee
      arthroplasty (TKA). Three hundred seventy-six OA patients scheduled to undergo
      TKA were included. Falls data within the preoperative, first postoperative and
      second postoperative years were collected, balance-related functions were
      assessed using the Assessment of Quality of Life (AQoL), WOMAC, Falls Efficacy
      Scale International (FES-I), Activities-specific Balance Confidence (ABC), knee
      extension strength, Berg Balance Scale (BBS) and Timed Up and Go (TUG) before
      surgery and 1 and 2 years after surgery. Compared with preoperative values, the
      incidence of falls significantly decreased (14.89%, 6.23% and 3.14% within the
      preoperative, first postoperative and second postoperative years, respectively)
      and the AQoL, WOMAC, FES-I, ABC, knee extension strength, BBS and TUG
      significantly improved after TKA. Logistic regression analysis revealed that
      Kellgren-Lawrence grade >= 3 of the contralateral knee was an independent risk
      factor for falls before and after TKA. Conclusively, primary TKA is associated
      with a reduced incidence of falls and improved balance-related functions, and the
      contralateral knee should be considered in the design of fall-prevention
      strategies in patients with OA.

PMID- 29185498
TI  - Activating electrochemical catalytic activity of bio-palladium by hybridizing
      with carbon nanotube as "e- Bridge".
AB  - Nano metal catalysts produced by bacteria has received increasing attention owing
      to its environmental friendly synthesis route. However, the formed metal
      nanoparticles are associated with poorly conductive cells and challenged to be
      electrochemically applied. In this study, Palladium (Pd) nanoparticles were
      synthesized by Shewanella oneidensis MR-1. We demonstrated the limitation of
      palladized cells (Pd-cells) serving as electro-catalysts can be relieved by
      hybridizing with the conductive carbon nanotubes (Pd-cells-CNTs hybrid). Compared
      to the Pd-cells, the electrochemical active surface area of Pd in Pd-cells-CNTs10
      (the ratio of Pd/CNTs is 1/10 w/w) were dramatically increased by 68 times to
      20.44 m2.g-1. A considerable enhancement of electrocatalytic activity was further
      confirmed for Pd-cells-CNTs10 as indicated by a 5-fold increase of steady state
      current density for nitrobenzene reduction at -0.55 V vs Ag/AgCl. These results
      indicate that the biogenetic palladium could has been an efficient electro
      catalyst but just limited due to lacking an electron transport path (e - Bridge).
      This finding may also be helpful to guide the way to electrochemically use other
      biogenetic metal nano-materials.

PMID- 29185499
TI  - The spectral, spatial and contrast sensitivity of human polarization pattern
      perception.
AB  - It is generally believed that humans perceive linear polarized light following
      its conversion into a luminance signal by diattenuating macular structures.
      Measures of polarization sensitivity may therefore allow a targeted assessment of
      macular function. Our aim here was to quantify psychophysical characteristics of
      human polarization perception using grating and optotype stimuli defined solely
      by their state of linear polarization. We show: (i) sensitivity to polarization
      patterns follows the spectral sensitivity of macular pigment; (ii) the change in
      sensitivity across the central field follows macular pigment density; (iii)
      polarization patterns are identifiable across a range of contrasts and scales,
      and can be resolved with an acuity of 15.4 cycles/degree (0.29 logMAR); and (iv)
      the human eye can discriminate between areas of linear polarization differing in
      electric field vector orientation by as little as 4.4 degrees . These findings,
      which support the macular diattenuator model of polarization sensitivity, are
      unique for vertebrates and approach those of some invertebrates with a well
      developed polarization sense. We conclude that this sensory modality extends
      beyond Haidinger's brushes to the recognition of quantifiable spatial
      polarization-modulated patterns. Furthermore, the macular origin and sensitivity
      of human polarization pattern perception makes it potentially suitable for the
      detection and quantification of macular dysfunction.

PMID- 29185500
TI  - A novel method for calculating the dynamic capillary force and correcting the
      pressure error in micro-tube experiment.
AB  - Micro-tube experiment has been implemented to understand the mechanisms of
      governing microcosmic fluid percolation and is extensively used in both fields of
      micro electromechanical engineering and petroleum engineering. The measured
      pressure difference across the microtube is not equal to the actual pressure
      difference across the microtube. Taking into account the additional pressure
      losses between the outlet of the micro tube and the outlet of the entire setup,
      we propose a new method for predicting the dynamic capillary pressure using the
      Level-set method. We first demonstrate it is a reliable method for describing
      microscopic flow by comparing the micro-model flow-test results against the
      predicted results using the Level-set method. In the proposed approach, Level-set
      method is applied to predict the pressure distribution along the microtube when
      the fluids flow along the microtube at a given flow rate; the microtube used in
      the calculation has the same size as the one used in the experiment. From the
      simulation results, the pressure difference across a curved interface (i.e.,
      dynamic capillary pressure) can be directly obtained. We also show that dynamic
      capillary force should be properly evaluated in the micro-tube experiment in
      order to obtain the actual pressure difference across the microtube.

PMID- 29185501
TI  - Random Combinatorial Gradient Metasurface for Broadband, Wide-Angle and
      Polarization-Independent Diffusion Scattering.
AB  - This paper proposes an easy, efficient strategy for designing broadband, wide
      angle and polarization-independent diffusion metasurface for radar cross section
      (RCS) reduction. A dual-resonance unit cell, composed of a cross wire and cross
      loop (CWCL), is employed to enhance the phase bandwidth covering the 2pi range.
      Both oblique-gradient and horizontal-gradient phase supercells are designed for
      illustration. The numerical results agree well with the theoretical ones. To
      significantly reduce backward scattering, the random combinatorial gradient
      metasurface (RCGM) is subsequently constructed by collecting eight supercells
      with randomly distributed gradient directions. The proposed metasurface features
      an enhanced specular RCS reduction performance and less design complexity
      compared to other candidates. Both simulated and measured results show that the
      proposed RCGM can significantly suppress RCS and exhibits broadband, wide-angle
      and polarization independence features.

PMID- 29185502
TI  - Selective uptake and sensing of nitrate in poly(3,4-ethylenedioxythiophene).
AB  - Nitrogen (N) as a nutrient, in the form of nitrate (NO3-), is essential for plant
      growth. Chemical fertilizers are used to increase crop yields, but overuse can
      lead to forms of environmental pollution necessitating methods to detect and
      monitor the level of NO3- in-situ in agricultural soils. Herein we report for the
      first time the NO3- selectivity of the inherently conducting polymer poly (3,4
      ethylenedioxythiophene) (PEDOT). This selectivity occurs when PEDOT thin films
      are exposed to an aqueous environment containing not only NO3-, but a mixture of
      other ions present in concentrations (ppm) typical of real agricultural soil. The
      PEDOT sensitivity to absorb NO3- from solution is determined to be <1 ppm.

PMID- 29185503
TI  - Publisher correction: Young inversion with multiple linked QTLs under selection
      in a hybrid zone.
AB  - In Fig. 5 of the version of this Article originally published, the final number
      on the x axes of each panel was incorrectly written as 1.5; it should have read
      7.5. This has now been corrected in all versions of the Article.

PMID- 29185504
TI  - Adaptive evolution by spontaneous domain fusion and protein relocalization.
AB  - Knowledge of adaptive processes encompasses understanding the emergence of new
      genes. Computational analyses of genomes suggest that new genes can arise by
      domain swapping; however, empirical evidence has been lacking. Here we describe a
      set of nine independent deletion mutations that arose during selection
      experiments with the bacterium Pseudomonas fluorescens in which the membrane
      spanning domain of a fatty acid desaturase became translationally fused to a
      cytosolic di-guanylate cyclase, generating an adaptive 'wrinkly spreader'
      phenotype. Detailed genetic analysis of one gene fusion shows that the mutant
      phenotype is caused by relocalization of the di-guanylate cyclase domain to the
      cell membrane. The relative ease by which this new gene arose, along with its
      functional and regulatory effects, provides a glimpse of mutational events and
      their consequences that are likely to have a role in the evolution of new genes.

PMID- 29185505
TI  - Worldwide patterns of human epigenetic variation.
AB  - DNA methylation is an epigenetic modification, influenced by both genetic and
      environmental variation, that plays a key role in transcriptional regulation and
      many organismal phenotypes. Although patterns of DNA methylation have been shown
      to differ between human populations, it remains to be determined how epigenetic
      diversity relates to the patterns of genetic and gene expression variation at a
      global scale. Here we measured DNA methylation at 485,000 CpG sites in five
      diverse human populations, and analysed these data together with genome-wide
      genotype and gene expression data. We found that population-specific DNA
      methylation mirrors genetic variation, and has greater local genetic control than
      mRNA levels. We estimated the rate of epigenetic divergence between populations,
      which indicates far greater evolutionary stability of DNA methylation in humans
      than has been observed in plants. This study provides a deeper understanding of
      worldwide patterns of human epigenetic diversity, as well as initial estimates of
      the rate of epigenetic divergence in recent human evolution.

PMID- 29185506
TI  - Host-specific infestation in early Cambrian worms.
AB  - Symbiotic relationships are widespread in terrestrial and aquatic animals today,
      but evidence of symbiosis in the fossil record between soft-bodied bilaterians
      where the symbiont is intimately associated with the integument of the host is
      extremely rare. The radiation of metazoan life apparent in the Ediacaran (~635
      541 million years ago) and Cambrian (~541-488 million years ago) periods is
      increasingly accepted to represent ecological diversification resulting from
      earlier key genetic developmental events and other innovations that occurred in
      the late Tonian and Cryogenian periods (~850-635 million years ago). The Cambrian
      has representative animals in each major ecospace category, the early Cambrian in
      particular having witnessed the earliest known complex animal communities and
      trophic structures, including symbiotic relationships. Here we report on newly
      discovered Cricocosmia and Mafangscolex worms that are hosts to aggregates of a
      new species of tiny worm in the lower Cambrian (Series 2, Stage 3) Chengjiang
      Lagerstatte of Yunnan Province, southwest China. The worm associations suggest
      the earliest known record of aggregate infestation of the integument of a soft
      bodied bilaterian, host specificity and host shift.

PMID- 29185507
TI  - Chromosomal inversion differences correlate with range overlap in passerine
      birds.
AB  - Chromosomal inversions evolve frequently but the reasons for this remain unclear.
      We used cytological descriptions of 411 species of passerine birds to identify
      large pericentric inversion differences between species, based on the position of
      the centromere. Within 81 small clades comprising 284 of the species, we found
      319 differences on the 9 largest autosomes combined, 56 on the Z chromosome, and
      55 on the W chromosome. We also identified inversions present within 32 species.
      Using a new fossil-calibrated phylogeny, we examined the phylogenetic,
      demographic and genomic context in which these inversions have evolved. The
      number of inversion differences between closely related species is consistently
      predicted by whether the ranges of species overlap, even when time is controlled
      for as far as is possible. Fixation rates vary across the autosomes, but
      inversions are more likely to be fixed on the Z chromosome than the average
      autosome. Variable mutagenic input alone (estimated by chromosome size, map
      length, GC content or repeat density) cannot explain the differences between
      chromosomes in the number of inversions fixed. Together, these results support a
      model in which inversions increase because of their effects on recombination
      suppression in the face of hybridization. Other factors associated with
      hybridization may also contribute, including the possibility that inversions
      contain incompatibility alleles, making taxa less likely to collapse following
      secondary contact.

PMID- 29185508
TI  - Direct and cascading impacts of tropical land-use change on multi-trophic
      biodiversity.
AB  - The conversion of tropical rainforest to agricultural systems such as oil palm
      alters biodiversity across a large range of interacting taxa and trophic levels.
      Yet, it remains unclear how direct and cascading effects of land-use change
      simultaneously drive ecological shifts. Combining data from a multi-taxon
      research initiative in Sumatra, Indonesia, we show that direct and cascading land
      use effects alter biomass and species richness of taxa across trophic levels
      ranging from microorganisms to birds. Tropical land use resulted in increases in
      biomass and species richness via bottom-up cascading effects, but reductions via
      direct effects. When considering direct and cascading effects together, land use
      was found to reduce biomass and species richness, with increasing magnitude at
      higher trophic levels. Our analyses disentangle the multifaceted effects of land
      use change on tropical ecosystems, revealing that biotic interactions on broad
      taxonomic scales influence the ecological outcome of anthropogenic perturbations
      to natural ecosystems.

PMID- 29185509
TI  - Genomic insights into the ancient spread of Lyme disease across North America.
AB  - Lyme disease is the most prevalent vector-borne disease in North America and
      continues to spread. The disease was first clinically described in the 1970s in
      Lyme, Connecticut, but the origins and history of spread of the Lyme disease
      bacteria, Borrelia burgdorferi sensu stricto (s.s.), are unknown. To explore the
      evolutionary history of B. burgdorferi in North America, we collected ticks from
      across the USA and southern Canada from 1984 to 2013 and sequenced the, to our
      knowledge, largest collection of 146 B. burgdorferi s.s. genomes. Here, we show
      that B. burgdorferi s.s. has a complex evolutionary history with previously
      undocumented levels of migration. Diversity is ancient and geographically
      widespread, well pre-dating the Lyme disease epidemic of the past ~40 years, as
      well as the Last Glacial Maximum ~20,000 years ago. This means the recent
      emergence of human Lyme disease probably reflects ecological change-climate
      change and land use changes over the past century-rather than evolutionary change
      of the bacterium.

PMID- 29185510
TI  - Perception costs of reproduction can magnify sexual selection.

PMID- 29185511
TI  - Environmental structuring of marine plankton phenology.
AB  - Seasonal cycles of primary production (phenology) critically influence
      biogeochemical cycles, ecosystem structure and climate. In the oceans, primary
      production is dominated by microbial phytoplankton that drift with currents, and
      show rapid turnover and chaotic dynamics, factors that have hindered
      understanding of their phenology. We used all available observations of upper
      ocean phytoplankton concentration (1995-2015) to describe global patterns of
      phytoplankton phenology, the environmental factors that structure them, and their
      relationships to terrestrial patterns. Phytoplankton phenologies varied strongly
      by latitude and productivity regime: those in high-production regimes were
      governed by insolation, whereas those in low-production regimes were constrained
      by vertical mixing. In eight of ten ocean regions, our findings contradict the
      hypothesis that phytoplankton phenologies are coherent at basin scales. Lastly,
      the spatial organization of phenological patterns in the oceans was broadly
      similar to those on land, suggesting an overarching effect of insolation on the
      phenology of primary producers globally.

PMID- 29185512
TI  - Female cuckoo calls misdirect host defences towards the wrong enemy.
AB  - Prey are sensitive to even subtle cues of predation risk, which provides the
      evolutionary potential for parasites to exploit host risk perception. Brood
      parasitic common cuckoos (Cuculus canorus) lay their eggs in the nests of host
      species and their secretive laying behaviour enables them to evade host defences.
      Therefore, it seems paradoxical that female cuckoos often give a conspicuous
      'chuckle' call after parasitizing a host's clutch. Here, we show that this hawk
      like chuckle call increases the success of parasitism by diverting host parents'
      attention away from the clutch and towards their own safety. In our field
      experiments, reed warbler (Acrocephalus scirpaceus) hosts paid no more attention
      to the 'cuck-oo' call of the male common cuckoo than the call of a harmless dove.
      However, the chuckle call of the female cuckoo had the same effect as the call of
      a predatory hawk in distracting the warblers' attention and reducing rejection of
      a foreign egg. Our results show that the female cuckoo enhances her success by
      manipulating a fundamental trade-off in host defences between clutch and self
      protection.

PMID- 29185513
TI  - Crafty cuckoo calls.

PMID- 29185514
TI  - Community-wide integration of floral colour and scent in a Mediterranean
      scrubland.
AB  - Angiosperm flowers have evolved a dazzling palette of colours and a rich bouquet
      of scents, principally serving to attract pollinators. Despite recent progress in
      the ecology of pollination, the sensory floral traits that are important for
      communication with pollinators (for example, colour and scent) have not been
      assessed in an unbiased, integrative sense within a community context.
      Nonetheless, floral sensory stimuli are known key factors that mediate flower
      visitation, thus affecting community dynamics. Here we show that flowers of the
      phrygana, a natural Mediterranean scrubland, display integrated patterns of scent
      composition and colour (as perceived by pollinators). Surprisingly, the data
      reveal predictive relationships between patterns of volatile composition and
      flower reflectance spectra. The presence of nectar is related to visual cues and
      the qualitative composition of floral aromas. Our results reveal a coordinated
      phenotypic integration consistent with the sensory abilities and perceptual
      biases of bees, suggesting potential facilitative effects for pollination and
      highlighting the fundamental importance of bees in Mediterranean-type ecosystems.
      We offer our unbiased approach as a starting point for more extensive, global
      investigations of the diversity of floral sensory phenotypes and its role in the
      community ecology of plant-pollinator interactions.

PMID- 29185515
TI  - Intermediate degrees of synergistic pleiotropy drive adaptive evolution in
      ecological time.
AB  - Rapid phenotypic evolution of quantitative traits can occur within years, but its
      underlying genetic architecture remains uncharacterized. Here we test the
      theoretical prediction that genes with intermediate pleiotropy drive adaptive
      evolution in nature. Through a resurrection experiment, we grew Arabidopsis
      thaliana accessions collected across an 8-year period in six micro-habitats
      representative of that local population. We then used genome-wide association
      mapping to identify the single-nucleotide polymorphisms (SNPs) associated with
      evolved and unevolved traits in each micro-habitat. Finally, we performed a
      selection scan by testing for temporal differentiation in these SNPs. Phenotypic
      evolution was consistent across micro-habitats, but its associated genetic bases
      were largely distinct. Adaptive evolutionary change was most strongly driven by a
      small number of quantitative trait loci (QTLs) with intermediate degrees of
      pleiotropy; this pleiotropy was synergistic with the per-trait effect size of the
      SNPs, increasing with the degree of pleiotropy. In addition, weak selection was
      detected for frequent micro-habitat-specific QTLs that shape single traits. In
      this population, A. thaliana probably responded to local warming and increased
      competition, in part mediated by central regulators of flowering time. This
      genetic architecture, which includes both synergistic pleiotropic QTLs and
      distinct QTLs within particular micro-habitats, enables rapid phenotypic
      evolution while still maintaining genetic variation in wild populations.

PMID- 29185516
TI  - A Devonian tetrapod-like fish reveals substantial parallelism in stem tetrapod
      evolution.
AB  - The fossils assigned to the tetrapod stem group document the evolution of
      terrestrial vertebrates from lobe-finned fishes. During the past 18 years the
      phylogenetic structure of this stem group has remained remarkably stable, even
      when accommodating new discoveries such as the earliest known stem tetrapod
      Tungsenia and the elpistostegid (fish-tetrapod intermediate) Tiktaalik. Here we
      present a large lobe-finned fish from the Late Devonian period of China that
      disrupts this stability. It combines characteristics of rhizodont fishes
      (supposedly a basal branch in the stem group, distant from tetrapods) with
      derived elpistostegid-like and tetrapod-like characters. This melange of
      characters may reflect either detailed convergence between rhizodonts and
      elpistostegids plus tetrapods, under a phylogenetic scenario deduced from
      Bayesian inference analysis, or a previously unrecognized close relationship
      between these groups, as supported by maximum parsimony analysis. In either case,
      the overall result reveals a substantial increase in homoplasy in the tetrapod
      stem group. It also suggests that ecological diversity and biogeographical
      provinciality in the tetrapod stem group have been underestimated.

PMID- 29185517
TI  - Author Correction: ISS observations offer insights into plant function.
AB  - In the version of this Comment previously published, in Box 1, the spacing of the
      GEDI footprints should have read 60 m along the track, not 25 m. Also the second
      affiliation for Susan Ustin was incorrect, she is only associated with the
      University of California, Davis. These errors have now been corrected.

PMID- 29185518
TI  - Deep faunistic turnovers preceded the rise of dinosaurs in southwestern Pangaea.
AB  - The Triassic period documents the origin and diversification of modern amniote
      lineages and the Late Triassic fossil record of South America has been crucial to
      shed light on these early evolutionary histories. However, the faunistic changes
      that led to the establishment of Late Triassic ecosystems are largely ignored
      because of the global scarcity of fossils from assemblages a few million years
      older. Here we contribute to fill this gap with the description of a new tetrapod
      assemblage from the lowermost levels of the Chanares Formation (uppermost Middle
      lower Late Triassic epochs) of Argentina, which is older than the other
      vertebrate assemblages of the same basin. The new assemblage is composed of
      therapsids, rhynchosaurids and archosaurs, and clearly differs from that of the
      immediately overlying and well-known historical Chanares vertebrate assemblage.
      The new tetrapod association is part of a phase of relatively rapidly changing
      vertebrate assemblage compositions, in a time span shorter than 6 million years,
      before the diversification of dinosaurs and other common Late Triassic tetrapods
      in southwestern Pangaea.

PMID- 29185519
TI  - The skull roof tracks the brain during the evolution and development of reptiles
      including birds.
AB  - Major transformations in brain size and proportions, such as the enlargement of
      the brain during the evolution of birds, are accompanied by profound
      modifications to the skull roof. However, the hypothesis of concerted evolution
      of shape between brain and skull roof over major phylogenetic transitions, and in
      particular of an ontogenetic relationship between specific regions of the brain
      and the skull roof, has never been formally tested. We performed 3D morphometric
      analyses to examine the deep history of brain and skull-roof morphology in
      Reptilia, focusing on changes during the well-documented transition from early
      reptiles through archosauromorphs, including nonavian dinosaurs, to birds. Non
      avialan taxa cluster tightly together in morphospace, whereas Archaeopteryx and
      crown birds occupy a separate region. There is a one-to-one correspondence
      between the forebrain and frontal bone and the midbrain and parietal bone.
      Furthermore, the position of the forebrain-midbrain boundary correlates
      significantly with the position of the frontoparietal suture across the
      phylogenetic breadth of Reptilia and during the ontogeny of individual taxa.
      Conservation of position and identity in the skull roof is apparent, and there is
      no support for previous hypotheses that the avian parietal is a transformed
      postparietal. The correlation and apparent developmental link between regions of
      the brain and bony skull elements are likely to be ancestral to Tetrapoda and may
      be fundamental to all of Osteichthyes, coeval with the origin of the
      dermatocranium.

PMID- 29185520
TI  - Gut-like ectodermal tissue in a sea anemone challenges germ layer homology.
AB  - Cnidarians (for example, sea anemones and jellyfish) develop from an outer
      ectodermal and inner endodermal germ layer, whereas bilaterians (for example,
      vertebrates and flies) additionally have a mesodermal layer as intermediate germ
      layer. Currently, cnidarian endoderm (that is, 'mesendoderm') is considered
      homologous to both bilaterian endoderm and mesoderm. Here we test this hypothesis
      by studying the fate of germ layers, the localization of gut cell types, and the
      expression of numerous 'endodermal' and 'mesodermal' transcription factor
      orthologues in the anthozoan sea anemone Nematostella vectensis. Surprisingly, we
      find that the developing pharyngeal ectoderm and its derivatives display a
      transcription-factor expression profile (foxA, hhex, islet, soxB1, hlxB9, tbx2/3,
      nkx6 and nkx2.2) and cell-type combination (exocrine and insulinergic)
      reminiscent of the developing bilaterian midgut, and, in particular, vertebrate
      pancreatic tissue. Endodermal derivatives, instead, display cell functions and
      transcription-factor profiles similar to bilaterian mesoderm derivatives (for
      example, somatic gonad and heart). Thus, our data supports an alternative model
      of germ layer homologies, where cnidarian pharyngeal ectoderm corresponds to
      bilaterian endoderm, and the cnidarian endoderm is homologous to bilaterian
      mesoderm.

PMID- 29185521
TI  - Ichnological evidence for meiofaunal bilaterians from the terminal Ediacaran and
      earliest Cambrian of Brazil.
AB  - The evolutionary events during the Ediacaran-Cambrian transition (~541 Myr ago)
      are unparalleled in Earth history. The fossil record suggests that most extant
      animal phyla appeared in a geologically brief interval, with the oldest
      unequivocal bilaterian body fossils found in the Early Cambrian. Molecular clocks
      and biomarkers provide independent estimates for the timing of animal origins,
      and both suggest a cryptic Neoproterozoic history for Metazoa that extends
      considerably beyond the Cambrian fossil record. We report an assemblage of
      ichnofossils from Ediacaran-Cambrian siltstones in Brazil, alongside U-Pb
      radioisotopic dates that constrain the age of the oldest specimens to 555-542
      Myr. X-ray microtomography reveals three-dimensionally preserved traces ranging
      from 50 to 600 MUm in diameter, indicative of small-bodied, meiofaunal
      tracemakers. Burrow morphologies suggest they were created by a nematoid-like
      organism that used undulating locomotion to move through the sediment. This
      assemblage demonstrates animal-sediment interactions in the latest Ediacaran
      period, and provides the oldest known fossil evidence for meiofaunal bilaterians.
      Our discovery highlights meiofaunal ichnofossils as a hitherto unexplored window
      for tracking animal evolution in deep time, and reveals that both meiofaunal and
      macrofaunal bilaterians began to explore infaunal niches during the late
      Ediacaran.

PMID- 29185522
TI  - Cnidarians layer up.

PMID- 29185523
TI  - Meiofauna mute the Cambrian Explosion.

PMID- 29185524
TI  - Multiscale scenarios for nature futures.

PMID- 29185526
TI  - New interventions are needed to save coral reefs.

PMID- 29185527
TI  - Permanent revolution.

PMID- 29185525
TI  - Primate archaeology evolves.
AB  - Since its inception, archaeology has traditionally focused exclusively on humans
      and our direct ancestors. However, recent years have seen archaeological
      techniques applied to material evidence left behind by non-human animals. Here,
      we review advances made by the most prominent field investigating past non-human
      tool use: primate archaeology. This field combines survey of wild primate
      activity areas with ethological observations, excavations and analyses that allow
      the reconstruction of past primate behaviour. Because the order Primates includes
      humans, new insights into the behavioural evolution of apes and monkeys also can
      be used to better interrogate the record of early tool use in our own, hominin,
      lineage. This work has recently doubled the set of primate lineages with an
      excavated archaeological record, adding Old World macaques and New World capuchin
      monkeys to chimpanzees and humans, and it has shown that tool selection and
      transport, and discrete site formation, are universal among wild stone-tool-using
      primates. It has also revealed that wild capuchins regularly break stone tools in
      a way that can make them difficult to distinguish from simple early hominin
      tools. Ultimately, this research opens up opportunities for the development of a
      broader animal archaeology, marking the end of archaeology's anthropocentric era.

PMID- 29185528
TI  - The coexistence problem revisited.

PMID- 29185529
TI  - Shifting from a fertilization-dominated to a warming-dominated period.
AB  - Carbon dioxide and nitrogen fertilization effects on ecosystem carbon
      sequestration may slow down in the future because of emerging nutrient
      constraints, climate change reducing the effect of fertilization, and expanding
      land use change and land management and disturbances. Further, record high
      temperatures and droughts are leading to negative impacts on carbon sinks. We
      suggest that, together, these two phenomena might drive a shift from a period
      dominated by the positive effects of fertilization to a period characterized by
      the saturation of the positive effects of fertilization on carbon sinks and the
      rise of negative impacts of climate change. We discuss the evidence and processes
      that are likely to be leading to this shift.

PMID- 29185530
TI  - How do you treat epilepsy in pregnancy?

PMID- 29185531
TI  - Head injury while on anticoagulation: Small numbers, big risks.

PMID- 29185532
TI  - Sharing notes with patients: A review of current practice and considerations for
      neurologists.
AB  - Improved patient engagement is a critical consideration in the new payment
      climate. Releasing progress notes for patients to view may improve patient
      involvement and engagement in their care. Patients perceive benefit from viewing
      physician progress notes. As initial studies involved only primary care
      physicians, specialist physicians may have specific considerations when releasing
      notes to patients. This article provides a framework for neurologists to
      implement a note release policy in their practice.

PMID- 29185533
TI  - Depression in epilepsy, migraine, and multiple sclerosis: Epidemiology and how to
      screen for it.
AB  - Purpose of review: To provide an overview of the epidemiology of depression in
      chronic neurologic conditions that can affect individuals throughout the lifespan
      (epilepsy, migraine, multiple sclerosis [MS]) and examine depression screening
      tools for adults with these conditions. Recent findings: Depression is common in
      neurologic conditions and can be associated with lower quality of life, higher
      health resource utilization, and poor adherence to treatment. It affects around
      20%-30% of those with epilepsy, migraine, and MS, and evidence for a
      bidirectional association exists for each of these conditions. Depression
      screening tools generally perform well in neurologic conditions, but are not
      without limitations. Summary: Depression is a major contributor to poor outcomes
      in epilepsy, migraine, and MS. Although psychiatric resources are scarce
      globally, this is no reason to ignore depression in neurologic conditions.
      Depression screening tools are available in neurology and should be considered in
      clinical practice.

PMID- 29185534
TI  - Mild brain injury and anticoagulants: Less is enough.
AB  - Background: Despite the higher theoretical risk of traumatic intracranial
      hemorrhage (ICH) in anticoagulated patients with mild head injury, the value of
      sequential head CT scans to identify bleeding remains controversial. This study
      evaluated the utility of 2 sequential CT scans at a 48-hour interval (CT1 and
      CT2) in patients with mild head trauma (Glasgow Coma Scale 13-15) taking oral
      anticoagulants. Methods: We retrospectively evaluated the clinical records of all
      patients on chronic anticoagulation treatment admitted to the emergency
      department for mild head injury. Results: A total of 344 patients were included,
      and 337 (97.9%) had a negative CT1. CT2 was performed on 284 of the 337 patients
      with a negative CT1 and was positive in 4 patients (1.4%), but none of the
      patients developed concomitant neurologic worsening or required neurosurgery.
      Conclusions: Systematic routine use of a second CT scan in mild head trauma in
      patients taking anticoagulants is expensive and clinically unnecessary.

PMID- 29185536
TI  - Swallow-induced syncope in 5 patients: Electrophysiologic evaluation during
      swallowing.
AB  - Background: We sought to characterize a cohort of participants with swallow
      induced syncope (SIS) with clinical and electrophysiologic evaluations. Methods:
      Using electrocardiographic monitoring and neurophysiologic methods of swallowing,
      we evaluated a cohort of 5 patients with SIS, 4 of whom had longitudinal follow
      up. Results: We determined electrophysiologically that the duration between the
      onset of swallow and a bradyarrhythmia or asystole is extremely short (2-3
      seconds) in SIS. Most participants with SIS do not have a neurologic or
      esophageal disorder. SIS can occur with different food types, in sitting or
      standing position, and has varying frequency in different participants. Permanent
      pacemaker placement is a curative measure in SIS. Conclusions: Our findings
      suggest that SIS is elicited by reflex afferent pathways originating in the
      oropharynx, rather than an esophageal origin, as previously proposed. Our
      longitudinally followed cohort with detailed clinical and electrophysiologic
      characterization should aid the clinician in the diagnosis and treatment of this
      potentially life-threatening condition.

PMID- 29185537
TI  - Erratum: Pimavanserin: A novel therapeutic option for Parkinson disease
      psychosis.
AB  - [This corrects the article on p. 157 in vol. 7.].

PMID- 29185538
TI  - The convergence of neurology and psychiatry.

PMID- 29185535
TI  - Behavioral therapy for Tourette syndrome and chronic tic disorders.
AB  - Purpose of review: To summarize behavioral interventions for the treatment of
      primary tic disorders. Recent findings: Although tics were attributed to a
      disordered weak volition, the shift towards neurobiological models of tic
      disorders also transformed nonpharmacologic treatment practices. Current
      international guidelines recommend habit reversal training, comprehensive
      behavioral intervention, and exposure and response prevention as first-line
      therapies for tics. Appropriate patient selection, including age and presence of
      comorbidities, are salient clinical features that merit consideration. Evidence
      for further behavioral interventions is also presented. Summary: Currently
      recommended behavioral interventions view tics as habitual responses that may be
      further strengthened through negative reinforcement. Although availability and
      costs related to these interventions may limit their effect, Internet-based and
      telehealth approaches may facilitate wide accessibility. Novel nonpharmacologic
      treatments that take different approaches, such as autonomic modulation or
      attention-based interventions, may also hold therapeutic promise.

PMID- 29185539
TI  - Progressive ataxia and palatal tremor.

PMID- 29185540
TI  - Functional movement disorders: Five new things.
AB  - Purpose of review: Functional movement disorders (FMD) are commonly seen in
      neurologic practice, but are associated with poor outcomes. Recent years have
      seen a resurgence of interest in this area, with new developments in
      pathophysiologic understanding and therapeutic management. Recent findings:
      Individuals with FMD are a psychologically heterogeneous group, with many
      individuals having no detectable psychopathology on symptom screening measures,
      and possibly significant etiologically relevant life events only revealed through
      in-depth interviews. A randomized trial of specialist intensive physical
      rehabilitation compared to community-based neurophysiotherapy in FMD has
      demonstrated moderate to large effect sizes for both physical and social
      functioning outcomes. Experimental evidence suggests an impairment in the neural
      systems conferring a sense of agency over movement in individuals with FMD, and
      may explain why movements that appear voluntary are not experienced as such.
      Summary: The prognosis of individuals with FMD may be improved with greater
      access to appropriately organized care and treatment.

PMID- 29185541
TI  - Acute paraplegia in a patient with repaired coarctation of aorta.

PMID- 29185542
TI  - Pimavanserin: A novel therapeutic option for Parkinson disease psychosis.
AB  - Purpose of review: In April 2016, the Food and Drug Administration (FDA) approved
      a first-in-class atypical antipsychotic medication called pimavanserin for the
      treatment of Parkinson disease psychosis (PDP). We aim to inform readers about
      its indications, effectiveness, and safety profile. Recent findings: Pimavanserin
      acts as an inverse agonist at serotonin 5-HT2A receptors and has negligible
      effects on other receptors, thereby avoiding the D2 receptor antagonism that can
      potentially worsen motor symptoms. Its FDA approval was based primarily on the
      results of a single randomized, placebo-controlled phase 3 trial. Summary: While
      pimavanserin appears to be a safe, effective, and well-tolerated therapeutic
      option for PDP, additional clinical trials and open-label extension studies are
      needed to determine the long-term safety and efficacy of this promising therapy.
      In the meantime, prescribers need to be aware of the possible adverse effects of
      pimavanserin including QT interval prolongation and a potential to cause a
      paradoxical worsening of symptoms.

PMID- 29185543
TI  - Anton syndrome as a result of MS exacerbation.

PMID- 29185544
TI  - Erratum: Author correction.
AB  - [This corrects the article on p. 433 in vol. 60, PMID: 28989919.].

PMID- 29185546
TI  - Timed up and go test at tap test and shunt surgery in idiopathic normal pressure
      hydrocephalus.
AB  - Background: The 3-meter Timed Up and Go test (TUG) is a reliable quantitative
      test for assessment of gait and balance. We aimed to establish an optimal
      threshold of TUG at the tap test for predicting outcomes 12 months after shunt
      surgery in patients with idiopathic normal pressure hydrocephalus (iNPH).
      Methods: The TUG was measured in a total of 151 patients with possible iNPH
      before and after a tap test and 12 months after shunt surgery. Among them, 81
      patients underwent ventriculoperitoneal shunt implantation (SINPHONI) and 70
      underwent lumboperitoneal shunt implantation (SINPHONI-2). The areas under the
      curve (AUCs), sensitivities, and specificities for predicting shunt effectiveness
      were assessed. Results: The simple differences of time on TUG at the tap test
      were significantly more accurate for predicting shunt effectiveness than percent
      improvement of time. The highest AUC for the synchronized moving cutoff point of
      TUG time was 0.81 (sensitivity 81.0%; specificity 81.6%) at the threshold of 5
      seconds in the SINPHONI-2. For predicting improvements of >=10 seconds 12 months
      after lumboperitoneal shunt implantation, the AUC was 0.90, and the sensitivity
      and specificity at the threshold of 5.6 seconds were 83.3% and 81.0%. Only for
      patients with a <5-second improvement at the tap test, ventriculoperitoneal shunt
      implantation conveyed significantly better improvements in TUG time 12 months
      after surgery than lumboperitoneal shunt implantation. Conclusions: An
      improvement of 5 seconds was a useful threshold of TUG time at the tap test for
      predicting a >=10-second improvement 12 months after shunt surgery, rather than
      the percent improvement of TUG time.

PMID- 29185545
TI  - Movement disorders and chronic psychosis: Five new things.
AB  - Purpose of review: To discuss selected peer-reviewed research articles published
      between 2014 and 2016 and highlight 5 clinically relevant messages related to
      hyperkinetic and hypokinetic movement disorders in patients with chronic
      psychosis. Recent findings: A recent population-based study complemented data
      from clinical trials in showing increased risk of developing extrapyramidal
      symptoms with antipsychotic use. A community service-based longitudinal study
      showed that dopamine transporter imaging could help identify subgroups of
      patients with parkinsonism associated with antipsychotics with a progressive
      course, potentially manageable with l-dopa. Data from recent noteworthy clinical
      trials showed that a new VMAT-2 inhibitor and, for pharmacologically refractory
      tardive dyskinesia, deep brain stimulation of the globus pallidus internus are
      promising interventions. Finally, a population-based study has confirmed that
      hyperkinesias (encompassing chorea, dystonia, and stereotypies) may be early
      predictors of psychosis even in childhood and adolescence. Summary: Movement
      disorders associated with new-generation antipsychotics, including widely used
      agents (e.g., aripiprazole), are not rare occurrences. Better monitoring is
      needed to assess their true effect on patients' quality of life and functioning
      and to prevent underascertainment.

PMID- 29185547
TI  - Role of MRI in early detection of stroke secondary to neurosyphilis in an elderly
      patient coinfected with HIV.

PMID- 29185549
TI  - Heath care utilization, access, and advocacy.

PMID- 29185548
TI  - Practice current: How do you treat neuromyelitis optica?

PMID- 29185550
TI  - Neurology and mental health.

PMID- 29185552
TI  - Erratum: Acute hemichorea as unusual first multiple sclerosis presentation.
AB  - [This corrects the article on p. e9 in vol. 7.].

PMID- 29185551
TI  - Wearable biosensors to monitor disability in multiple sclerosis.
AB  - Purpose of review: Biosensors capable of measuring physiologic and kinetic
      parameters associated with disability are being applied to the study of people
      with multiple sclerosis (MS). We review the use of biosensors in people with MS
      with an emphasis on measuring/monitoring disability and understanding knowledge
      gaps between biosensor data and clinical care. Recent findings: Accelerometers
      are available to the public and may be able to help the clinician understand a
      patient's degree of disability. Further studies with wearable biosensors capable
      of measuring other physiologic features, such as vital signs, are needed and are
      likely to contribute to our understanding of MS. Summary: Wearable biosensors can
      improve our understanding of disability, response to treatment, and natural
      history of MS.

PMID- 29185553
TI  - Neurologists should endorse active transportation for their patients.
AB  - It has been well-established that social determinants prevent far more deaths
      than medical care. Both behavior and social circumstance are closely linked to
      transportation. The connection between health and transportation is both direct
      (pedestrian injury, for example) and indirect (commuting access to work leading
      to employer-based health insurance, for example). Thus, transportation policy and
      health policy are interrelated. Neurologists should join community partnerships
      to promote safe and healthy transportation options for all people but especially
      for their patients.

PMID- 29185554
TI  - Pure lemniscal sensory stroke.

PMID- 29185555
TI  - Perspectives on marijuana use and effectiveness: A survey of NARCOMS
      participants.
AB  - Background: Interest in and use of marijuana by persons with multiple sclerosis
      (MS) has increased. While potential benefits have been reported, so have concerns
      about potential risks. Few large studies have been conducted about the
      perceptions and current usage of marijuana and medical cannabinoids in persons
      with MS. Methods: Participants in the North American Research Committee on
      Multiple Sclerosis (NARCOMS) registry were surveyed in 2014 regarding legality
      and history of marijuana usage, both before and after diagnosis with MS. Results:
      A total of 5,481 participants responded, with 78.2% female, 90% relapsing disease
      at onset, and a current mean age of 55.5 (10.2) years. Sixty-four percent had
      tried marijuana prior to their MS diagnosis, 47% have considered using for their
      MS, 26% have used for their MS, 20% have spoken with their physician about use,
      and 16% are currently using marijuana. Ninety-one percent think marijuana should
      be legal in some form. Men, those with higher disability, current and past
      nicotine smokers, and younger age were associated with a higher likelihood of
      current use. Conclusions: The majority of responders favor legalization and
      report high interest in the use of marijuana for treatment of MS symptoms, but
      may be reluctant to discuss this with health care providers. Health care
      providers should systematically inquire about use of marijuana.

PMID- 29185556
TI  - Online tools for individuals with depression and neurologic conditions: A scoping
      review.
AB  - Background: Patients with neurologic conditions commonly have depression. Online
      tools have the potential to improve outcomes in these patients in an efficient
      and accessible manner. We aimed to identify evidence-informed online tools for
      patients with comorbid neurologic conditions and depression. Methods: A scoping
      review of online tools (free, publicly available, and not requiring a
      facilitator) for patients with depression and epilepsy, Parkinson disease (PD),
      multiple sclerosis (MS), traumatic brain injury (TBI), or migraine was conducted.
      MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane
      CENTRAL Register of Controlled Trials were searched from database inception to
      January 2017 for all 5 neurologic conditions. Gray literature using Google and
      Google Scholar as well as app stores for both Android and Apple devices were
      searched. Self-management or self-efficacy online tools were not included unless
      they were specifically targeted at depression and one of the neurologic
      conditions and met the other eligibility criteria. Results: Only 4 online tools
      were identified. Of these 4 tools, 2 were web-based self-management programs for
      patients with migraine or MS and depression. The other 2 were mobile apps for
      patients with PD or TBI and depression. No online tools were found for epilepsy.
      Conclusions: There are limited depression tools for people with neurologic
      conditions that are evidence-informed, publicly available, and free. Future
      research should focus on the development of high-quality, evidence-based online
      tools targeted at neurologic patients.

PMID- 29185558
TI  - Analytical solution of the PELDOR inverse problem using the integral Mellin
      transform.
AB  - We describe a new model-free approach to solve the inverse problem in pulsed
      double electron-electron resonance (PELDOR, also known as DEER) spectroscopy and
      obtain the distance distribution function between two radicals from time-domain
      PELDOR data. The approach is based on analytical solutions of the Fredholm
      integral equations of the first kind using integral Mellin transforms to provide
      the distance distribution function directly. The approach appears to confine the
      noise in the computed distance distribution to short distances and does not
      introduce systematic distortions. Thus, the proposed analysis method can be a
      useful supplement to current methods to determine complicated distance
      distributions.

PMID- 29185557
TI  - Frequency, determinants, and effects of early seizures after thrombolysis for
      acute ischemic stroke: The ENCHANTED trial.
AB  - Background: Seizures after ischemic stroke have not been well-studied. We aim to
      determine the frequency, determinants, and significance of early seizures after
      thrombolysis for acute ischemic stroke. Methods: Data are from the Enhanced
      Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an
      international, multicenter, randomized controlled trial where patients with acute
      ischemic stroke were randomized to low-dose (0.6 mg/kg) or standard-dose (0.9
      mg/kg) IV alteplase. The protocol prespecified prospective data collection on in
      hospital seizures over 7 days postrandomization. Logistic regression models were
      used to determine variables associated with seizures and their significance on
      poor outcomes of death or disability (modified Rankin scale scores 3-6),
      symptomatic intracerebral hemorrhage (sICH), and European Quality of Life 5
      Dimensions questionnaire [EQ-5D] over 90 days. Results: Data were available for
      3,139 acute ischemic stroke participants, of whom 42 (1.3%) had seizures at a
      median 22.7 hours after the onset of symptoms. Baseline variables associated with
      seizures were male sex (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.07
      4.50), severe neurologic impairment (NIH Stroke Scale score >=10; OR 2.16, 95% CI
      1.06-4.40), and fever (OR 4.55, 95% CI 2.37-8.71). Seizures independently
      predicted poor recovery: death or major disability (OR 2.88, 95% CI 1.28-6.47),
      unfavorable ordinal shift of mRS scores (OR 1.94, 95% CI 1.10-3.39), and lower
      than median EQ-5D health utility index score (OR 3.50, 95% CI 1.37-8.91). There
      was no association of seizures with sICH in adjusted analysis. Conclusions: In
      thrombolysis-treated patients with acute ischemic stroke, seizures are uncommon,
      occur early, and predict poor recovery. Clinicaltrialsgov identifier:
      NCT01422616.

PMID- 29185559
TI  - Quantitative evaluation of analyte transport on microfluidic paper-based
      analytical devices (MUPADs).
AB  - The transport efficiency during capillary flow-driven sample transport on
      microfluidic paper-based analytical devices (MUPADs) made from filter paper has
      been investigated for a selection of model analytes (Ni2+, Zn2+, Cu2+, PO43-,
      bovine serum albumin, sulforhodamine B, amaranth) representing metal cations,
      complex anions, proteins and anionic molecules. For the first time, the transport
      of the analytical target compounds rather than the sample liquid, has been
      quantitatively evaluated by means of colorimetry and absorption spectrometry
      based methods. The experiments have revealed that small paperfluidic channel
      dimensions, additional user operation steps (e.g. control of sample volume,
      sample dilution, washing step) as well as the introduction of sample liquid
      wicking areas allow to increase analyte transport efficiency. It is also shown
      that the interaction of analytes with the negatively charged cellulosic paper
      substrate surface is strongly influenced by the physico-chemical properties of
      the model analyte and can in some cases (Cu2+) result in nearly complete analyte
      depletion during sample transport. The quantitative information gained through
      these experiments is expected to contribute to the development of more sensitive
      MUPADs.

PMID- 29185560
TI  - Correction: A study of separation selectivity using embedded ester-bonded
      stationary phases for liquid chromatography.
AB  - Correction for 'A study of separation selectivity using embedded ester-bonded
      stationary phases for liquid chromatography' by Szymon Bocian et al., Analyst,
      2016, 141, 4340-4348.

PMID- 29185562
TI  - Few-layered titanate nanosheets with large lateral size and surface
      functionalization: potential for the controlled exfoliation of inorganic-organic
      layered composites.
AB  - Herein, few-layered titanate nanosheets with a large lateral size and surface
      functionalization were synthesized via the exfoliation of precursor layered
      composites in an organic medium. The combination of layered compounds,
      intercalated guests, and dispersion media has the potential for the synthesis of
      nanosheets with controlled lateral sizes, thicknesses, and surface chemistry
      through exfoliation.

PMID- 29185563
TI  - Adsorption and diffusion of hydrogen and oxygen in FCC-Co: a first-principles
      study.
AB  - Hydrogen and oxygen play an important role in the hydrogen embrittlement and
      oxidation of novel Co-based alloys with gamma/gamma' microstructure. In this
      study, the adsorption of hydrogen and oxygen atoms on the FCC-Co(111) surface and
      their diffusion behavior from the surface into the sub-layers and bulk have been
      investigated by means of first-principles calculations. It is observed that
      hydrogen and oxygen atoms prefer to adsorb on the fcc and hcp (threefold hollow)
      sites, respectively. The hydrogen atom can penetrate into the first and second
      sub-layers energetically, while it is not feasible for the oxygen atom as
      diffusion from the surface into the first sub-layer is more difficult. It is
      found that the calculated diffusion coefficients of hydrogen are in good
      agreement with the available experimental data. Finally, we briefly discuss the
      changes in total magnetic moment along the Oct-Tet-Oct diffusion path and the
      associated electronic structures. The present work is helpful to provide
      comprehensive guidance for the development and applications of novel Co-based
      alloys.

PMID- 29185561
TI  - Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor
      associated macrophage uptake in metastatic disease.
AB  - The receptor tyrosine kinase Mer (MERTK) is a promising drug target in cancer,
      where it can influence the metastasis-promoting signaling of both tumor cells and
      immune cells alike; however, no small molecule probes currently exist to
      selectively image Mer. In this work, we design and synthesize a selective near
      infrared fluorescent molecular probe of Mer (MERi-SiR). Confocal microscopy of
      metastases in mice reveals predominant probe accumulation in Mer-expressing tumor
      associated macrophages.

PMID- 29185564
TI  - Identifying the structure of 4-chlorophenyl isocyanide adsorbed on Au(111) and
      Pt(111) surfaces by first-principles simulations of Raman spectra.
AB  - Surface Raman spectroscopy has become one of the most powerful analytical tools
      for interfacial structures. However, theoretical modeling for the Raman spectra
      of molecular adsorbate on metallic surfaces is a long-standing challenge because
      accurate descriptions of the electronic structure for both the metallic
      substrates and adsorbates are required. Here we present a quasi-analytical method
      for high-precision surface Raman spectra at the first principle level. Using this
      method, we correlate both geometrical and electronic structures of a single 4
      chlorophenyl isocyanide (CPI) molecule adsorbed on a Au(111) or Pt(111) surface
      with its Raman spectra. The "finger-print" frequency shift of the CN stretching
      mode reveals the in situ configuration of CPI is vertical adsorption on the top
      site of the Au(111) surface, but a bent configuration when it adsorbs on the
      hollow site of the Pt(111) surface. Electronic structure calculations reveal that
      a pi-back donation mechanism often causes a red shift to the Raman response of CN
      stretching mode. In contrast, sigma donation as well as a wall effect introduces
      a blue shift to the CN stretching mode. A clear relationship for the dependence
      of Raman spectra on the surface electronic and geometrical information is built
      up, which largely benefits the understanding of chemical and physical changes
      during the adsorption. Our results highlight that high-precision theoretical
      simulations are essential for identifying in situ geometrical and electronic
      surface structures.

PMID- 29185566
TI  - Fluctuation enhancement of ion diffusivity in liquids.
AB  - The diffusivity of ions in liquid solutions is known either to decrease with an
      increase in the ion size or to have a single maximum depending on the ion size.
      This article presents evidence for the appearance of multiple maxima and thus
      multiple ion sizes with enhanced diffusivity. This is caused by destabilization
      of the ion solvation shell and only happens at the ion radii that correspond to
      changes of the ion coordination number, which happen with an increase in the ion
      size. Solvation shell fluctuations are activated which leads to additional ion
      motion with rearrangement of the shell. A theoretical model of this effect is
      derived and is shown to be in good agreement with molecular dynamics and
      experimental data. This result rewrites a long standing picture of ion transport
      as a function of ion size and introduces a new possibility in the search for
      highly conductive systems.

PMID- 29185568
TI  - Phase behaviour and thermodynamics: general discussion.

PMID- 29185571
TI  - Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP
      cells through the modulation of the TRPV1 channel.
AB  - Capsaicin (CAP), a potent transient receptor potential vanilloid type 1 (TRPV1)
      agonist, is a major ingredient of red pepper. Recently, capsaicin has attracted
      increasing attention owing to its multiple biological activities. However, the
      anticancer effects of capsaicin against various types of cancers, especially on
      thyroid carcinoma, have not been completely elucidated. TRPV1, which can be
      activated by capsaicin, plays a key role in many biological and physiological
      processes. In the present study, the anticancer properties of capsaicin against
      papillary thyroid cancer BCPAP cells were investigated. Our results indicated
      that TRPV1 and TRPV6 were universally expressed in different types of thyroid
      cell lines. Capsaicin could inhibit multiple steps of metastasis without
      affecting the viability of BCPAP cells. The activation of TRPV1 by capsaicin (25
      100 MUM) significantly suppressed the migration and invasion of BCPAP cells as
      well as their adhesion. The protein levels of Snail1 and Twist1, two critical EMT
      transcription factors (EMT-TFs), dramatically decreased in a dose-dependent
      manner after capsaicin treatment, accompanied by the up-regulation of downstream
      protein E-cadherin. Subsequently, the activation of TRPV1 by capsaicin also
      caused significant inhibition of the expression of MMP-2 and MMP-9. Moreover, the
      inhibitory effects of capsaicin on the metastasis of BCPAP cells were abrogated
      by the pre-treatment of a specific TRPV1 antagonist (capsazepin). Our results
      suggest that the activation of TRPV1 by capsaicin is associated with the
      metastatic inhibition of papillary thyroid cancer BCPAP cells, indicating that
      targeting of TRPV1 functions remains a feasible strategy for cancer treatment.

PMID- 29185572
TI  - Thermoelectric properties and thermal stability of layered chalcogenides, TlScQ2,
      Q = Se, Te.
AB  - A few thallium based layered chalcogenides of alpha-NaFeO2 structure-type are
      known for their excellent thermoelectric properties and interesting topological
      insulator nature. TlScQ2 belongs to this structural category. In the present
      work, we have studied the electronic structure, electrical and thermal transport
      properties and thermal stability of the title compounds within the temperature
      range 2-600 K. Density functional theory (DFT) predicts a metallic nature for
      TlScTe2 and a semiconducting nature for TlScSe2. DFT calculations also show
      significant lowering of energies of frontier bands upon inclusion of spin-orbit
      coupling contribution in the calculation. The electronic structure also shows the
      simultaneous occurrence of holes and electron pockets for the telluride.
      Experiments reveal that the telluride shows a semi-metallic behaviour whereas the
      selenide is a semiconductor. The thermoelectric properties for both the materials
      were also investigated. Both these materials possess very low thermal
      conductivity which is an attractive feature for thermoelectrics. However, they
      lack thermal stability and decompose upon warming above room temperature, as
      evidenced from high temperature powder X-ray diffraction and thermal analysis.

PMID- 29185573
TI  - A light-driven modulation of electric conductance through the adsorption of
      azobenzene onto silicon-doped- and pyridine-like N3-vacancy graphene.
AB  - The ability to modulate the conductance of an electronic device under light
      irradiation is crucial to the practical applications of nanoscale electronics.
      Density functional theory calculations predict that the conductance of the photo
      responsive graphene-based nanocomposites can be tuned through the noncovalent
      adsorption of an azobenzene (AB) derivative onto pristine, Si-doped, and pyridine
      like N3-vacancy graphene. AB@graphene systems were found to exhibit a visible
      light response within the low-frequency region, rendering the trans-to-cis
      isomerizations of these nanocomposites under the irradiation of solar light. The
      excellent solar light absorption performances of these hybrids can then be used
      to modulate the conductance of both N3-vacancy- and Si-doped-graphene AB hybrids
      effectively through the reversible change of the effective conjugate length of
      the AB molecule in the photoisomerization. In addition, the solar thermal energy
      up to 1.53 eV per AB molecule can be stored in the designed nanocomposites with
      the doped graphene. These findings provide clues for making multifunctional
      materials with potential applications as both optically controlled
      nanoelectronics and solar energy storage devices.

PMID- 29185574
TI  - Colchicine metallocenyl bioconjugates showing high antiproliferative activities
      against cancer cell lines.
AB  - A series of ferrocenyl and ruthenocenyl conjugates with colchicine bearing a
      1,2,3-triazole moiety were synthesized and their anticancer properties were
      evaluated. We found that the most potent metallocenyl derivatives Rc4 and Rc5 are
      6-7 times more cytotoxic toward HepG2 cells, while Fc4 and Fc5 are two times more
      cytotoxic toward HCT116 cells as colchicine. We also found that compounds Fc4,
      Fc5, Rc1 and Rc3-Rc5 are able to induce apoptosis, while compound Fc2 arrests
      mitosis.

PMID- 29185575
TI  - Osteoinductive superparamagnetic Fe nanocrystal/calcium phosphate
      heterostructured microspheres.
AB  - Functional magnetic and biocompatible particles are of great interest because of
      their potential use in various bioapplications such as hyperthermia for cancer
      treatment, magnetic resonance imaging (MRI) contrast agents and drug delivery.
      Herein, we introduce a facile method for synthesizing magnetic Fe nanocrystal/Fe
      substituted calcium phosphate (Fe/FeCaP) heterostructured microspheres using a
      two-step procedure: (1) one-pot hydrothermal synthesis to prepare uniform-sized
      FeCaP microspheres and (2) post-reduction annealing at 600  degrees C for Fe
      extraction from FeCaP. This approach results in the fabrication of Fe/FeCaP
      heterostructured microspheres that exhibit superparamagnetism with a saturation
      magnetization of 10.77 emu g-1. The Fe/FeCaP particles annealed at 600  degrees C
      show a much higher magnetic moment compared with the non-annealed FeCaP
      particles. Moreover, T2-weighted MRI phantom images reveal that the Fe/FeCaP
      heterostructured microspheres possess higher relaxivity than paramagnetic FeCaP,
      demonstrating their potential as superior and biocompatible MRI contrast agents.
      Moreover, the enhancement in osteoconductivity for Fe/FeCaP microspheres without
      any evidence of cytotoxicity was verified. Our results demonstrate the great
      potential of multi-functional Fe/FeCaP microspheres for use as biocompatible bone
      regeneration agents as well as MRI contrast agents.

PMID- 29185576
TI  - In situ/operando characterization techniques for rechargeable lithium-sulfur
      batteries: a review.
AB  - Rechargeable lithium-sulfur (Li-S) batteries have recently attracted global
      research interest due to their high theoretical specific capacity and energy
      density. To improve the performance and cycling stability of Li-S batteries, a
      clear understanding of the electrochemical reaction process and the degradation
      mechanisms of the sulfur redox chemistry are extremely important. In the past few
      decades, various advanced in situ/operando characterization tools have emerged,
      which have facilitated the understanding of the degradation mechanisms and the
      further development of high-performance Li-S batteries. In this review, we have
      summarized recent significant advances in in situ/operando characterization
      techniques for Li-S batteries. In particular, because of the existence of the
      soluble polysulfide species during the charge/discharge process, many creative
      ideas have been introduced into in situ/operando characterization of the
      electrochemical process in Li-S batteries.

PMID- 29185577
TI  - Comparative investigation of sensing behaviors between gap and lattice plasmon
      modes in a metallic nanoring array.
AB  - Plasmonic nanostructures have become the most promising candidates for biosensing
      applications because of their miniature sizes, ease of integration, and high
      throughput detection. Both propagating and localized surface plasmon modes in the
      nanostructures have been used for sensing and biomolecular detection. However, to
      maximize the biosensing potential of nanostructures, the choice of an optimized
      sensing detection strategy among two plasmon modes depends on the relationship
      between the biomolecule sizes and field decay length of plasmon modes. Here, we
      propose and investigate plasmonic coupling on a single-crystalline gold film,
      wherein there are two distinct optical modes, a gap mode (localized surface
      plasmon) originating from the parallel coupling of a nanoring and a surface
      lattice mode (propagating surface plasmon) originating from the anti-parallel
      coupling of a nanoring in an array. The sensing performances of the above two
      modes are thoroughly investigated and compared by considering two aspects, i.e.,
      bulk and surface sensitivities. It is demonstrated that there is a reciprocal
      relationship between bulk and surface sensitivities for two modes, which also
      illustrates that the surface sensitivity is indispensable to fully describe the
      sensing performance of nanostructures. Furthermore, due to their different decay
      lengths, the gap and surface lattice modes on a single optical substrate can
      achieve simultaneous detection of target analytes with various sizes. Therefore,
      we can provide a high performance sensing platform based on a metallic nanoring
      array for a broad range of biomolecules with various sizes.

PMID- 29185578
TI  - A spin crossover (SCO) active graphene-iron(ii) complex hybrid material.
AB  - The advancement of molecular electronics and spintronics requires novel hybrid
      materials with synergistic magnetic and electrical properties. The non-covalent
      functionalization of highly conductive graphene with magnetically bistable spin
      crossover (SCO) complexes may yield such a multifunctional material. In this
      regard, a graphene-Fe(ii) SCO complex hybrid (Gr-SCO) has been prepared by non
      covalently anchoring a pyrene decorated SCO complex with solution phase pre
      exfoliated few-layer graphene sheets. SQUID magnetometry revealed the
      preservation of SCO in the Gr-SCO hybrid material exhibiting more gradual spin
      state switching characteristics than in the bulk molecular complex. This
      persistence of SCO of a molecular Fe(ii) complex upon anchoring on the graphene
      surface has consequences towards the realization of SCO based applications: in
      (i) reversible spin state dependent band gap tuning of graphene with an SCO
      complex analogous to chemical doping of graphene, and (ii) to probe the spin
      state dependence of electrical conductivity modulation by wiring the anchoring
      group (pyrene) tethered SCO complex between chemically robust few-layer graphene
      electrodes.

PMID- 29185579
TI  - Subnanometer structure and function from ion beams through complex fluidics to
      fluorescent particles.
AB  - The vertical dimensions of complex nanostructures determine the functions of
      diverse nanotechnologies. In this paper, we investigate the unknown limits of
      such structure-function relationships at subnanometer scales. We begin with a
      quantitative evaluation of measurement uncertainty from atomic force microscopy,
      which propagates through our investigation from ion beam fabrication to
      fluorescent particle characterization. We use a focused beam of gallium ions to
      subtractively pattern silicon surfaces, and silicon nitride and silicon dioxide
      films. Our study of material responses quantifies the atomic limits of forming
      complex topographies with subnanometer resolution of vertical features over a
      wide range of vertical and lateral dimensions. Our results demonstrate the
      underutilized capability of this standard system for rapid prototyping of
      subnanometer structures in hard materials. We directly apply this unprecedented
      dimensional control to fabricate nanofluidic devices for the analytical
      separation of colloidal nanoparticles by size exclusion. Optical microscopy of
      single nanoparticles within such reference materials establishes a subnanometer
      limit of the fluidic manipulation of particulate matter and enables critical
      dimension particle tracking with subnanometer accuracy. After calibrating for
      optical interference within our multifunctional devices, which also enables
      device metrology and integrated spectroscopy, we reveal an unexpected
      relationship between nanoparticle size and emission intensity for common
      fluorescent probes. Emission intensity increases supervolumetrically with
      nanoparticle diameter and then decreases as nanoparticles with different
      diameters photobleach to similar values of terminal intensity. We propose a
      simple model to empirically interpret these surprising results. Our investigation
      enables new control and study of structure-function relationships at subnanometer
      scales.

PMID- 29185584
TI  - Monomer diffusion into static and evolving polymer networks during frontal
      photopolymerisation.
AB  - Frontal photopolymerisation (FPP) is a directional solidification process that
      converts monomer-rich liquid into crosslinked polymer solid by light exposure and
      finds applications ranging from lithography to 3D printing. Inherent to this
      process is the creation of an evolving polymer network that is exposed to a
      monomer bath. A combined theoretical and experimental investigation is performed
      to determine the conditions under which monomer from this bath can diffuse into
      the propagating polymer network and cause it to swell. First, the growth and
      swelling processes are decoupled by immersing pre-made polymer networks into
      monomer baths held at various temperatures. The experimental measurements of the
      network thickness are found to be in good agreement with theoretical predictions
      obtained from a nonlinear poroelastic model. FPP propagation experiments are then
      carried out under conditions that lead to swelling. Unexpectedly, for a fixed
      exposure time, swelling is found to increase with incident light intensity. The
      experimental data is well described by a novel FPP model accounting for mass
      transport and the mechanical response of the polymer network, providing key
      insights into how monomer diffusion affects the conversion profile of the polymer
      solid and the stresses that are generated during its growth. The predictive
      capability of the model will enable the fabrication of gradient materials with
      tuned mechanical properties and controlled stress development.

PMID- 29185588
TI  - Fasting: a major limitation for resistance exercise training effects in rodents.
AB  - Protocols that mimic resistance exercise training (RET) in rodents present
      several limitations, one of them being the electrical stimulus, which is beyond
      the physiological context observed in humans. Recently, our group developed a
      conditioning system device that does not use electric shock to stimulate rats,
      but includes fasting periods before each RET session. The current study was
      designed to test whether cumulative fasting periods have some influence on
      skeletal muscle mass and function. Three sets of male Wistar rats were used in
      the current study. The first set of rats was submitted to a RET protocol without
      food restriction. However, rats were not able to perform exercise properly. The
      second and third sets were then randomly assigned into three experimental groups:
      1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3)
      rats submitted to RET including fasting periods before each RET session. While
      the second set of rats performed a short RET protocol (i.e., an adaptation
      protocol for 3 weeks), the third set of rats performed a longer RET protocol
      including overload (i.e., 8 weeks). After the short-term protocol, cumulative
      fasting periods promoted loss of weight (P<0.001). After the longer RET protocol,
      no difference was observed for body mass, extensor digitorum longus (EDL)
      morphology or skeletal muscle function (P>0.05 for all). Despite no effects on
      EDL mass, soleus muscle displayed significant atrophy in the fasting experimental
      groups (P<0.01). Altogether, these data indicate that fasting is a major
      limitation for RET in rats.

PMID- 29185589
TI  - Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain
      metastases due to non-small-cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are
      usually associated with poor prognostic outcomes. This retrospective study
      proposed to assess whether bevacizumab or gefitinib can be used to improve the
      effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain
      metastases. A total of 218 NSCLC patients with multiple brain metastases were
      retrospectively included in this study and were randomly allocated to bevacizumab
      gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75).
      Then, tumor responses were evaluated every 2 months based on Response Evaluation
      Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic
      examination were documented every 6 months after the treatment. Compared to the
      standard WBRT, bevacizumab and gefitinib could significantly enhance response
      rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR
      and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than
      those who received gefitinib-WBRT. The overall survival (OS) rates and
      progression-free survival (PFS) rates also differed significantly among the
      bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and
      WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was
      slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested
      by prolonged PFS and OS status, bevacizumab substantially improved the overall
      efficacy of WBRT in the management of patients with NSCLC.

PMID- 29185590
TI  - Short-term effects of stored homologous red blood cell transfusion on
      cardiorespiratory function and inflammation: an experimental study in a
      hypovolemia model.
AB  - The pathophysiological mechanisms associated with the effects of red blood cell
      (RBC) transfusion on cardiopulmonary function and inflammation are unclear. We
      developed an experimental model of homologous 14-days stored RBC transfusion in
      hypovolemic swine to evaluate the short-term effects of transfusion on
      cardiopulmonary system and inflammation. Sixteen healthy male anesthetized swine
      (68+/-3.3 kg) were submitted to controlled hemorrhage (25% of blood volume). Two
      units of non-filtered RBC from each animal were stored under blood bank
      conditions for 14 days. After 30 min of hypovolemia, the control group (n=8)
      received an infusion of lactated Ringer's solution (three times the removed
      volume). The transfusion group (n=8) received two units of homologous 14-days
      stored RBC and lactated Ringer's solution in a volume that was three times the
      difference between blood removed and blood transfusion infused. Both groups were
      followed up for 6 h after resuscitation with collection of hemodynamic and
      respiratory data. Cytokines and RNA expression were measured in plasma and lung
      tissue. Stored RBC transfusion significantly increased mixed oxygen venous
      saturation and arterial oxygen content. Transfusion was not associated with
      alterations on pulmonary function. Pulmonary concentrations of cytokines were not
      different between groups. Gene expression for lung cytokines demonstrated a 2
      fold increase in mRNA level for inducible nitric oxide synthase and a 0.5-fold
      decrease in mRNA content for IL-21 in the transfused group. Thus, stored
      homologous RBC transfusion in a hypovolemia model improved cardiovascular
      parameters but did not induce significant effects on microcirculation, pulmonary
      inflammation and respiratory function up to 6 h after transfusion.

PMID- 29185591
TI  - Safety and efficacy of regional citrate anticoagulation in continuous blood
      purification treatment of patients with multiple organ dysfunction syndrome.
AB  - The aim of this study was to discuss the safety and efficacy of regional citrate
      anticoagulation (RCA) on continuous blood purification (CBP) during the treatment
      of multiple organ dysfunction syndrome (MODS). Thirty-five patients with MODS
      were divided into two groups: the local citrate anticoagulation (RCA) group, and
      the heparin-free blood purification (hfBP) group. The MODS severity was assessed
      according to Marshall's MODS score criteria. Blood coagulation indicators, blood
      pressure, filter lifespan, filter replacement frequency, anticoagulation
      indicators, and main metabolic and electrolyte indicators were analyzed and
      compared between RCA and hfBP groups. RCA resulted in lower blood pressure than
      hfBP. The filter efficacy in RCA treatment was longer than in the hfBP group. The
      blood clearance of creatine, blood urea nitrogen and uric acid was better in the
      RCA group. RCA also led to higher pH than hfBP. Neither treatment resulted in
      severe bleeding events. In addition, MODS score was positively correlated with
      prothrombin time and activated partial thromboplastin time but negatively
      correlated with platelet concentration. RCA is a safer and more effective method
      in CBP treatment; however, it could also lead to low blood pressure and blood
      alkalosis.

PMID- 29185592
TI  - Decellularization of placentas: establishing a protocol.
AB  - Biological biomaterials for tissue engineering purposes can be produced through
      tissue and/or organ decellularization. The remaining extracellular matrix (ECM)
      must be acellular and preserve its proteins and physical features. Placentas are
      organs of great interest because they are discarded after birth and present large
      amounts of ECM. Protocols for decellularization are tissue-specific and have not
      been established for canine placentas yet. This study aimed at analyzing a
      favorable method for decellularization of maternal and fetal portions of canine
      placentas. Canine placentas were subjected to ten preliminary tests to analyze
      the efficacy of parameters such as the type of detergents, freezing temperatures
      and perfusion. Two protocols were chosen for further analyses using histology,
      scanning electron microscopy, immunofluorescence and DNA quantification. Sodium
      dodecyl sulfate (SDS) was the most effective detergent for cell removal. Freezing
      placentas before decellularization required longer periods of incubation in
      different detergents. Both perfusion and immersion methods were capable of
      removing cells. Placentas decellularized using Protocol I (1% SDS, 5 mM EDTA, 50
      mM TRIS, and 0.5% antibiotic) preserved the ECM structure better, but Protocol I
      was less efficient to remove cells and DNA content from the ECM than Protocol II
      (1% SDS, 5 mM EDTA, 0.05% trypsin, and 0.5% antibiotic).

PMID- 29185593
TI  - Behavioral cross-sensitization between testosterone and fenproporex in adolescent
      and adult rats.
AB  - The abuse of psychoactive drugs is considered a global health problem. During the
      last years, a relevant number of studies have investigated the relationship
      between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS,
      such as testosterone, can cause a dependence syndrome that shares many features
      with the classical dependence to psychoactive substances. Pre-clinical evidence
      shows that there are interactions between testosterone and psychoactive drugs,
      such as cocaine. However, few studies have been performed to investigate the
      effect of repeated testosterone treatment on behavioral effects of amphetamine
      derivatives, such as fenproporex. The purpose of the present study was to
      investigate the effects of repeated testosterone administration on fenproporex
      induced locomotor activity in adolescent and adult rats. Adolescent male Wistar
      rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days,
      animals received an acute injection of fenproporex (3.0 mg/kg ip) and the
      locomotor activity was recorded during 40 min. Thirty days later, the same
      animals received the same treatment with testosterone followed by a fenproporex
      challenge injection as described above. Our results demonstrated that repeated
      testosterone induced behavioral sensitization to fenproporex in adolescent but
      not in adult rats. These findings suggest that repeated AAS treatment might
      increase the dependence vulnerability to amphetamine and its derivatives in
      adolescent rats.

PMID- 29185594
TI  - Simple protocol for population (Sanger) sequencing for Zika virus genomic
      regions.
AB  - BACKGROUND: A number of Zika virus (ZIKV) sequences were obtained using Next
      generation sequencing (NGS), a methodology widely applied in genetic diversity
      studies and virome discovery. However Sanger method is still a robust,
      affordable, rapid and specific tool to obtain valuable sequences. OBJECTIVE: The
      aim of this study was to develop a simple and robust Sanger sequencing protocol
      targeting ZIKV relevant genetic regions, as envelope protein and nonstructural
      protein 5 (NS5). In addition, phylogenetic analysis of the ZIKV strains obtained
      using the present protocol and their comparison with previously published NGS
      sequences were also carried out. METHODS: Six Vero cells isolates from serum and
      one urine sample were available to develop the procedure. Primer sets were
      designed in order to conduct a nested RT-PCR and a Sanger sequencing protocols.
      Bayesian analysis was used to infer phylogenetic relationships. FINDINGS: Seven
      complete ZIKV envelope protein (1,571 kb) and six partial NS5 (0,798 Kb) were
      obtained using the protocol, with no amplification of NS5 gene from urine sample.
      Two NS5 sequences presented ambiguities at positions 495 and 196. Nucleotide
      analysis of a Sanger sequence and consensus sequence of previously NGS study
      revealed 100% identity. ZIKV strains described here clustered within the Asian
      lineage. MAIN CONCLUSIONS: The present study provided a simple and low-cost
      Sanger protocol to sequence relevant genes of the ZIKV genome. The identity of
      Sanger generated sequences with published consensus NGS support the use of Sanger
      method for ZIKV population studies. The regions evaluated were able to provide
      robust phylogenetic signals and may be used to conduct molecular epidemiological
      studies and monitor viral evolution.

PMID- 29185595
TI  - First evidence of Zika virus venereal transmission in Aedes aegypti mosquitoes.
AB  - BACKGROUND: Aedes aegypti is considered the main Zika virus (ZIKV) vector, and is
      thought to be responsible for the 2015-2016 outbreak in Brazil. Zika positive Ae.
      aegypti males collected in the field suggest that vertical and/or venereal
      transmission of ZIKV may occur. OBJECTIVES: In this study, we aimed to
      demonstrate that venereal transmission of ZIKV by Ae. aegypti can occur under
      laboratory conditions. METHODS: Ae. aegypti collected in the city of Manaus,
      confirmed as negative for Zika, Dengue and Chikungunya virus by reverse
      transcription real-time polymerase chain reaction (RT-qPCR) (AaM3V- strain), were
      reared under laboratory conditions and used for the experiments. The ZIKV used in
      this study was isolated from a patient presenting with symptoms; ZIKV was
      confirmed by RT-qPCR. Experiment 1: virgin male mosquitoes of AaM3V- strain were
      intrathoracically inoculated with a ZIKV suspension; four days after injection,
      they were transferred to a cage containing virgin females of AaM3V- strain and
      left to copulate for five days. Experiment 2: virgin female mosquitoes of AaM3V-
      strain were orally infected with a ZIKV suspension by blood feeding membrane
      assay; nine days after blood feeding, they were placed in cages with Ae. aegypti
      AaM3V- virgin males and left to copulate for four days. After copulation, all
      mosquitoes were individually evaluated for viral infection by RT-qPCR. FINDINGS:
      The mean infection rate in Experiment 1 and Experiment 2 was 45% and 35%,
      respectively. In both experiments, cycle threshold values ranged from 13 to 35,
      indicating the presence of viral genomes. MAIN CONCLUSION: Ae. aegypti males
      intrathoracically inoculated with a ZIKV suspension are infected and can transmit
      the virus to uninfected females by mating. Moreover, Ae. aegypti females orally
      infected with a ZIKV suspension can transmit the virus to uninfected males by
      copulation. This study shows that ZIKV infection of Ae. aegypti mosquitoes occurs
      not only during blood feeding, but also during copulation.

PMID- 29185596
TI  - Single shot of 17D vaccine may not confer life-long protection against yellow
      fever.
AB  - The yellow fever (YF) vaccine has been used since the 1930s to prevent YF, which
      is a severe infectious disease caused by the yellow fever virus (YFV), and mainly
      transmitted by Culicidae mosquitoes from the genera Aedes and Haemagogus . Until
      2013, the World Health Organization (WHO) recommended the administration of a
      vaccine dose every ten years. A new recommendation of a single vaccine dose to
      confer life-long protection against YFV infection has since been established.
      Recent evidence published elsewhere suggests that at least a second dose is
      needed to fully protect against YF disease. Here, we discuss the feasibility of
      administering multiple doses, the necessity for a new and modern vaccine, and
      recommend that the WHO conveys a meeting to discuss YFV vaccination strategies
      for people living in or travelling to endemic areas.

PMID- 29185597
TI  - Urgent call for action: avoiding spread and re-urbanisation of yellow fever in
      Brazil.

PMID- 29185598
TI  - Elements of the socio-critical paradigm in nursing care practices: an integrative
      review.
AB  - OBJECTIVE: Analyze the evidence available in Brazilian theses on the elements of
      the socio-critical paradigm in the construction of knowledge and practices of
      nursing care. METHOD: An integrative literature review was carried out in the
      Theses Database of the Coordination for the Improvement of Higher Education
      Personnel and the Brazilian Digital Library of Theses and Dissertations. RESULTS:
      Of a total of 320 theses, only 19 had elements of the socio-critical paradigm in
      their construction, among which the use of participatory investigations stand out
      (especially action-research), which present interaction between the researcher
      and the participants, the use of data collection techniques such as focus groups
      and culture circles, and theoretical frameworks for analyzing the phenomena in
      their complexity. CONCLUSION: The support of the sociocritical paradigm
      attributes to nursing the character of a practical science and service to the
      community, being committed to social transformation by empowering people.

PMID- 29185599
TI  - Alcohol use and health behavior among nursing professionals.
AB  - OBJECTIVE: To evaluate the problematic use of alcohol and health behavior among
      the nursing staff of a general hospital. METHOD: Cross-sectional study conducted
      at a general hospital. A questionnaire with socio-demographic information, the
      alcohol and substance use screening test, and a questionnaire on health behavior
      were applied. RESULTS: A total of 416 professionals participated in the study. In
      the final model of logistical regression, male professionals (OR 4.3), singles
      (OR 3.7), those that professed to having other religions (OR 3.8), worked as
      nursing technician (OR 2.3), did not consume low doses of alcoholic beverages per
      day (OR 2.0), used tobacco (OR 8.9), avoided consuming beverages with caffeine
      (OR 1.9) and avoided noisy environments (OR 2.0) showed higher chances of
      consuming alcohol at a problematic level. CONCLUSION: Among nursing
      professionals, the use of alcohol and not engaging in health behavior are
      strongly associated. These findings have implications for the implementation of
      strategies for the promotion of health and the prevention of alcohol use in work
      relationships.

PMID- 29185600
TI  - Indications of comprehensiveness in the pedagogical relationship: a design to be
      constructed in nursing education.
AB  - OBJECTIVE: To analyze how the indications of comprehensiveness translate into the
      teaching-learning process in a nursing undergraduate course. METHOD: Qualitative
      case study carried out with professors of a Nursing Undergraduate Course. Data
      collection occurred through documentary analysis, non-participant observation and
      individual interviews. Data analysis was guided from an analytical matrix
      following the steps of the operative proposal. RESULTS: Eight professors
      participated in the study. Some indications of comprehensiveness such as
      dialogue, listening, mutual respect, bonding and welcoming are present in the
      daily life of some professors. The indications of comprehensiveness are applied
      by some professors in the pedagogical relationship. The results refer to the
      Comprehensiveness of teaching-learning in a single and double loop model, and in
      this the professor and the student assume an open posture for new possibilities
      in the teaching-learning process. CONCLUSION: Comprehensiveness, as it is
      recognized as a pedagogical principle, allows the disruption of a professor
      centered teaching and advances in collective learning, enabling the professor and
      student to create their own design anchored in a reflective process about their
      practices and the reality found in the health services.

PMID- 29185601
TI  - Adherence to central venous catheter insertion bundle in neonatal and pediatric
      units.
AB  - OBJECTIVE: To describe the observed behavior of professionals in two neonatal and
      pediatric intensive care units regarding the use of central venous catheter
      insertion bundle, and the clinical and birth profile of neonates and children who
      received the devices. METHOD: A quantitative descriptive exploratory study was
      conducted in two intensive care units of a public hospital in Belo Horizonte with
      neonates and children, between February and September 2016. RESULTS: The sample
      consisted of 59 observed implants of central venous catheter. Most patients were
      male preterm infants, of cesarean delivery and proper weight according to the
      gestational age. Among all procedures observed, only three followed all
      recommendations for the central venous catheter insertion bundle. Incorrect
      techniques were observed while performing surgical antisepsis and inadequate use
      of chlorhexidine, an antiseptic. CONCLUSION: The findings highlight the
      importance of more investment in continuous training of the team on the
      prevention of bloodstream infection caused by central venous catheter to reduce
      the number of adverse events related to intravenous therapy.

PMID- 29185602
TI  - The first study of molecular prevalence and species characterization of
      Cryptosporidium in free-range chicken (Gallus gallus domesticus) from Brazil.
AB  - Rearing free-range chicken is based on grazing feeding patterns, and these
      animals could be potential environmental contaminants of Cryptosporidium oocysts
      for humans and other animals. Therefore, the present study aimed to evaluate the
      molecular prevalence of Cryptosporidium spp. in free-range chickens from Brazil.
      A total of 351 fecal samples from chickens were examined from 20 farms. For
      detection of Cryptosporidium spp., 18S rRNA gene fragments were amplified using a
      nested PCR reaction. Positive samples were sent for sequencing. The overall
      prevalence of Cryptosporidium was 25.6% (95% CI = 21.2% - 30.6%). Sequencing of
      the amplified fragments allowed for the identification of three species: C.
      meleagridis in 57 (62.6%), C. baileyi in 15 (16.4%), C. parvum in 3 (3.2%)
      samples, and a new Cryptosporidium genotype (C. genotype BrPR1) in 3 (3.2%)
      samples. Cryptosporidium genotype BrPR1 has not yet been classified as a species,
      and its host spectrum is not known. Cryptosporidium, including zoonotic species,
      exists at a high prevalence in free-range chickens within the region studied.

PMID- 29185603
TI  - Influence of biofilm formation on the mechanical properties of enamel after
      treatment with CPP-ACP creme.
AB  - The study aimed to investigate the effects of bacterial biofilms on changes in
      the surface microhardness of enamel treated with casein phosphopeptide-amorphous
      calcium phosphate (CPP-ACP) with and without fluoride. Human enamel blocks with
      incipient caries-like lesions were divided into four groups of 13: G1: Saliva
      (Control); G2: fluoride dentifrice (CrestTM, 1100 ppm as NaF); G3: CPP-ACP (MI
      Paste; RecaldentTM); and G4: CPP-ACPF (MI Paste Plus; RecaldentTM 900 ppm as
      NaF). The specimens were soaked in demineralizing solution for 6 h and
      remineralized in artificial saliva for 18 h alternately for 10 days. The
      dentifrice was prepared with deionized water in a 1 : 3 ratio (w/w) or applied
      undiluted in the case of the CPP-ACP group. The surface microhardness (SMH) was
      evaluated at baseline, after artificial caries, after pH cycling and treatment
      with dentifrices, and after incubation in media with Streptococcus mutans for
      biofilm formation. The biofilms were exposed once a day to 2% sucrose and the
      biofilm viability was measured by MTT reduction. The percentage of change in
      surface microhardness (%SMHC) was calculated for each block. The data were
      analyzed by nonparametric test comparisons (alpha = 0.05). The %SMHC values
      observed in G2 were different from those of G1, G3, and G4 (p < 0.05). After
      biofilm formation, %SMHC was positive in G2 and G4 when compared to G1 and G3,
      but resistance to demineralization after biofilm formation was similar in all
      groups. In conclusion, the presence of biofilms did not influence the treatment
      outcomes of anticaries products.

PMID- 29185604
TI  - Glycemic control and adipokines after periodontal therapy in patients with Type 2
      diabetes and chronic periodontitis.
AB  - The mechanism by which chronic periodontitis (CP) affects type 2 diabetes (T2DM)
      remains unclear. Therefore, the aim of this study is to evaluate the effects of
      periodontal therapy (PT) on the glycemic control and adipokines of patients with
      T2DM and CP with the purpose of elucidating the possible mechanisms by which CP
      influences T2DM. Forty-four patients with T2DM and CP were randomly divided into
      two groups according to whether they underwent PT. Periodontal status, blood
      glucose, and the levels of serum tumor necrosis factor alpha (TNF-alpha),
      interleukin-6 (IL-6), adiponectin (APN), and fibroblast growth factor-21 (FGF-21)
      were measured at baseline and after 3 months. The results revealed that the
      probing depth (PD) and attachment loss (AL) were significantly improved, the
      serum levels of TNF-alpha and IL-6 were significantly decreased, and APN and FGF
      21 exhibited substantial increases in the intervention group after 3 months (p <
      0.05), whereas no significant changes were observed in the control group. The
      glycated hemoglobin (HbA1c) levels in both groups decreased significantly after 3
      months compared with baseline (p < 0.05), but the intervention group exhibited a
      significantly greater change (p < 0.05). In conclusion, PT may relieve
      periodontal inflammation, which causes a reduction of insulin-antagonizing
      adipokines and an increase in insulin-sensitizing adipokines, thereby eliciting
      an improvement in glycemic control.

PMID- 29185605
TI  - The use of tools to support oral lesion description in oral medicine referrals.
AB  - Poor description of oral lesions jeopardize the prioritization of appointments in
      Oral Medicine. The present study investigated whether the use of support tools
      changes the quality of descriptions focusing on health care prioritization. Two
      oral lesions (A and B) were described by 64 dental students and 48 dentists using
      three methods: (a) without support tools (free); (b) using the oral examination
      form from the Specialties Manual in Oral Health/Brazilian Ministry of Health
      (SMOH form); and (c) using the OralDESC guideline. The descriptions were compared
      with a gold standard and percentage of agreement was analyzed by the Kruskal
      Wallis and Dunn's tests (p<0.05). Descriptions with the OralDESC presented higher
      information quality. Considering items essential for prioritization, the OralDESC
      demonstrated better performance for lesion A; for lesion B, free descriptions and
      descriptions using the OralDESC were of higher quality than those using SMOH
      form. Therefore, the OralDESC offered greater support for the description of oral
      lesions for health care prioritization in Oral Medicine.

PMID- 29185606
TI  - The implications of different lateral wall thicknesses on surgical access to the
      maxillary sinus.
AB  - The objective of this study was to measure the topographic thickness of the
      lateral wall of the maxillary sinus in selected Asian populations. Measurements
      were made on the lateral walls of maxillary sinuses recorded using CBCT in a
      convenient sample of patients attending an Asian teaching hospital. The points of
      measurement were the intersections between the axes along the apices of the
      canine, first premolar, and second premolar and along the mesiobuccal and
      distobuccal apices of the first and second molars and horizontal planes 10 mm, 20
      mm, 30 mm and 40 mm beneath the orbital floor. The CBCT images of 109 patients
      were reviewed. The mean age of the patients was 33.0 (SD 14.8) years. Almost
      three quarters (71.8%) of the patients were male. The mean bone thickness
      decreased beginning at the 10-mm level and continuing to 40 mm below the orbital
      floor. Few canine regions showed encroachment of the maxillary sinus. The
      thickness of the buccal wall gradually increased from the canine region (where
      sinus encroachment of the canine region was present) to the first molar region,
      after which it decreased to the thickness observed at the canine region. The
      buccal wall of the maxillary sinus became thicker anteroposteriorly, except in
      the region of the second molar, and thinner superoinferiorly. These changes will
      affect the approach used to osteotomize the lateral sinus wall for oral surgery
      and for the sinus lift procedure.

PMID- 29185607
TI  - CAD/CAM Restorations: Achieving Excellence and Simplicity.

PMID- 29185608
TI  - Basil, tea tree and clove essential oils as analgesics and anaesthetics in
      Amphiprion clarkii (Bennett, 1830).
AB  - In this study were evaluated the anaesthesia and analgesic effects of clove
      Eugenia caryophyllata, tea tree Melaleuca alternifolia and basil Ocimum basilicum
      essential oils (EO) during handling of yellowtail clownfish Amphiprion clarkii.
      Juveniles (3.70 +/- 0.75 cm and 1.03 +/- 0.50 g; mean +/- standard deviation)
      were submitted to concentrations of 40, 50, 60, 70 and 80 ul L-1 of clove, 150,
      200, 250, 300 and 350 ul L-1 of basil and 200, 300, 400, 500 and 600 ul L-1 of
      tea tree oils (n=10/concentration), previously defined in pilot tests.
      Individually and only once, fish from each treatment were placed in a glass
      recipient containing 1 L of seawater at a temperature of 25  degrees C, salinity
      of 35 g L-1 and the specific concentration of diluted EO (stock solution).
      Control (only seawater) and blank (seawater and ethanol at the highest
      concentration used to dilute the oils) treatments were also conducted. After
      reaching the stage of surgical anaesthesia, fish were submitted to biometry and a
      sensibility test. After that, they were transferred to clean seawater for
      anaesthesia recovery. The times of induction needed to reach each anaesthesia
      stage and anaesthesia recovery were recorded. Animals were observed for 72 hours
      after the procedures. All the EO provoked anaesthesia and analgesic effects in A.
      clarkii, but basil oil is not recommended because it caused involuntary muscle
      contractions and mortality in 100% and 12% of fish, respectively. The lower
      concentrations that promote suitable induction and recovery times are 50 ul L-1
      of clove oil and 500 ul L-1 of tea tree oil. However, due to its complementary
      high analgesic efficiency, clove oil is recommended as the ideal anaesthetic for
      A. clarkii.

PMID- 29185609
TI  - Soil macrofauna density and diversity across a chronosequence of tropical forest
      restoration in Southeastern Brazil.
AB  - Edaphic macrofauna must be better studied if we want to take advantage of their
      full potential for the restoration of tropical ecosystems. We investigated
      changes in edaphic macrofauna density and diversity along a secondary succession
      chronosequence in the Atlantic Forest. Our results show some clear patterns of
      change in soil macrofauna along the chronosequence. Density did not increase
      along secondary succession, but was correlated with canopy cover. Diversity was
      characterized by high dominance of social insects and evenness among other
      groups. We conclude soil macrofauna has a high capacity to recolonize young
      forests and that its recovery is considerably fast compared to other ecosystem
      transformations.

PMID- 29185610
TI  - Reproductive dynamics of Lycengraulis grossidens (Clupeiformes: Engraulidae) and
      Platanichthys platana (Clupeiformes: Clupeidae) in a subtropical coastal lagoon.
AB  - We evaluated the reproductive dynamics of two fish species, Lycengraulis
      grossidens and Platanichthys platana, in a subtropical freshwater coastal lagoon
      (Peri Lagoon) in Brazil. Samples were collected from nine sites every two months
      from June 2008 to April 2012. Different fishing methods were used to capture
      larvae, juveniles, and adults. Limnological variables were obtained using
      multiparameter probe. More females than males were collected of both fish species
      and the chi-square test (chi2) was used to confirm that the sex ratio was female
      biased. Large numbers of maturing and mature fishes were observed in almost every
      sampling month. The gonadosomatic index (GSI) of L. grossidens was the highest in
      August, October, and December for females and in October for males, and no
      significant difference was found across years. The GSI of P. platana showed no
      significant difference across months for either sex; however, significant
      differences were recorded in year three (June 2010-April 2011) and year four
      (June 2011-April 2012) for females and in year three (June 2010-April 2011) for
      males. For both species, GSI was negatively correlated with temperature and water
      level. L. grossidens larvae were more abundant in October 2010, showing a
      positive correlation with water transparency, whereas P. platana larvae were more
      abundant in June 2011, showing a positive correlation with water transparency and
      negative correlation with temperature and precipitation. Both species were
      represented by different stages, including larvae, which confirm that these
      species reproduce in Peri Lagoon. Reproduction was more pronounced in autumn and
      winter; however, reproductive activity was evident throughout the sampling
      period. In conclusion, our results show that abiotic factors strongly influence
      the temporal pattern of reproductive activity and larval assemblages of both L.
      grossidens and P. platana in Peri Lagoon, Brazil.

PMID- 29185611
TI  - Occurrence of Metacaligus rufus (Wilson, 1908) (Copepoda, Caligidae) parasitizing
      the cownose ray Rhinoptera bonasus (Mitchill, 1815) (Elasmobranchii,
      Myliobatidae) in Brazil.

PMID- 29185612
TI  - Intestinal parasites in cancer patients in the South of Brazil.
AB  - Intestinal parasitic infections in immunocompromised patients can lead to serious
      complications when not diagnosed and treated early. This study aimed to
      investigate the frequency of intestinal parasites in cancer patients undergoing
      chemotherapy in the South of Brazil. Three fecal samples collected from each
      patient (73 individuals) were processed by Ritchie and Faust techniques and
      submitted to specific staining methods for intestinal protozoa. A 61.6% parasite
      and/or commensal positivity was found. Helminths identified were Ascaris
      lumbricoides (33.3%), Taenia spp. (6.6%), Strongyloides stercoralis (4.4%) and
      Trichuris trichiura (2.2%). Among protozoans, Giardia lamblia (26.6%),
      Cryptosporidium spp. (13.3%) and Cystoisospora belli (4.4%) were identified. The
      presence of Entamoeba coli, Endolimax nana and Entamoeba hartmanni was also
      recorded. The results obtained warn of the importance of fecal parasitological
      diagnosis and the use of specific staining methods for the detection of
      intestinal parasites in cancer patients. These exams should be regularly
      requested at the patient's first clinic visit, given the high prevalence found in
      this study and the possible severity of such conditions for these individuals.

PMID- 29185613
TI  - Waist Circumference is Associated with Blood Pressure in Children with Normal
      Body Mass Index: A Cross-Sectional Analysis of 3,417 School Children.
AB  - BACKGROUND: The prevalence of childhood obesity and associated conditions, such
      as hypertension, has become a major problem of public health. Although waist
      circumference (WC) is a marker of cardiovascular risk in adults, it is unclear
      whether this index is associated with cardiovascular risk factors in children.
      OBJECTIVE: Our aim was to evaluate the association between increased WC and
      elevated blood pressure (BP) in children with normal body mass index (BMI)
      ranges. METHODS: Cross-sectional evaluation of students between 6 and 11 years
      with normal BMI. WC was categorized by quartile for each age group. Normal BP was
      defined as values < 90th percentile, and levels above this range were considered
      elevated. Values of p < 0.05 were considered statistically significant. RESULTS:
      Of the 5,037 children initially assessed, 404 (8%) were excluded for being
      underweight and 1,216 (24.1%) were excluded for being overweight or obese. A
      final sample of 3,417 children was evaluated. The prevalence of elevated BP was
      10.7%. In children with WC in the lowest quartile, the prevalence of elevated BP
      was 8.1%. This prevalence increased in upper quartiles: 10.6% in the second,
      12.4% in third and 12.1% in the upper quartile. So, in this group, being in the
      highest WC quartile was associated with a 57% higher likelihood to present
      elevated BP when compared to those in the lowest quartile (Q4 vs Q1; OR 1.57 -
      95%CI 1.14 - 2.17). CONCLUSION: In children aged 6 to 11 years, increased waist
      circumference is associated with elevated BP even when BMI is normal.

PMID- 29185614
TI  - Permanent Pacing After Transcatheter Aortic Valve Implantation: Incidence,
      Predictors and Evolution of Left Ventricular Function.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a well-established
      procedure; however, atrioventricular block requiring permanent pacemaker
      implantation (PPI) is a common complication. OBJECTIVES: To determine the
      incidence, predictors and clinical outcomes of PPI after TAVI, focusing on how
      PPI affects left ventricular ejection fraction (LVEF) after TAVI. METHODS: The
      Brazilian Multicenter TAVI Registry included 819 patients submitted to TAVI due
      to severe aortic stenosis from 22 centers from January/2008 to January/2015.
      After exclusions, the predictors of PPI were assessed in 670 patients by use of
      multivariate regression. Analysis of the ROC curve was used to measure the
      ability of the predictors; p < 0.05 was the significance level adopted. RESULTS:
      Within 30 days from TAVI, 135 patients (20.1%) required PPI. Those patients were
      older (82.5 vs. 81.1 years; p = 0.047) and mainly of the male sex (59.3% vs 45%;
      p = 0.003). Hospital length of stay was longer in patients submitted to PPI (mean
      = 15.7 +/- 25.7 vs. 11.8 +/- 22.9 days; p < 0.001), but PPI affected neither all
      cause death (26.7% vs. 25.6%; p = 0.80) nor cardiovascular death (14.1% vs.
      14.8%; p = 0.84). By use of multivariate analysis, the previous presence of right
      bundle-branch block (RBBB) (OR, 6.19; 3.56-10.75; p <= 0.001), the use of
      CoreValve(r) prosthesis (OR, 3.16; 1.74-5.72; p <= 0.001) and baseline
      transaortic gradient > 50 mm Hg (OR, 1.86; 1.08-3.2; p = 0.025) were predictors
      of PPI. The estimated risk of PPI ranged from 4%, when none of those predictors
      was present, to 63%, in the presence of all of them. The model showed good
      ability to predict the need for PPI: 0.69 (95%CI: 0.64 - 0.74) in the ROC curve.
      The substudy of 287 echocardiograms during the 1-year follow-up showed worse LVEF
      course in patients submitted to PPI (p = 0.01). CONCLUSION: BRD previo, gradiente
      aortico medio > 50 mmHg e CoreValve(r) sao preditores independentes de implante
      de MPD pos-TAVI. Ocorreu implante de MPD em aproximadamente 20% dos casos de
      TAVI, o que prolongou a internacao hospitalar, mas nao afetou a mortalidade. O
      implante de MPD afetou negativamente a FEVE pos-TAVI.

PMID- 29185615
TI  - Predictors of Total Mortality and Echocardiographic Response for Cardiac
      Resynchronization Therapy: A Cohort Study.
AB  - BACKGROUND: Clinical studies demonstrate that up to 40% of patients do not
      respond to cardiac resynchronization therapy (CRT), thus, appropriate patient
      selection is critical to the success of CRT in heart failure. OBJECTIVE:
      Evaluation of mortality predictors and response to CRT in the Brazilian scenario.
      METHODS: Retrospective cohort study including patients submitted to CRT in a
      tertiary hospital in southern Brazil from 2008 to 2014. Survival was assessed
      through a database of the State Department of Health (RS). Predictors of
      echocardiographic response were evaluated using Poisson regression. Survival
      analysis was performed by Cox regression and Kaplan Meyer curves. A two-tailed p
      value less than 0.05 was considered statistically significant. RESULTS: A total
      of 170 patients with an average follow-up of 1011 +/- 632 days were included. The
      total mortality was 30%. The independent predictors of mortality were age (hazard
      ratio [HR] of 1.05, p = 0.027), previous acute myocardial infarction (AMI) (HR of
      2.17, p = 0.049) and chronic obstructive pulmonary disease (COPD) (HR of 3.13, p
      = 0.015). The percentage of biventricular stimulation at 6 months was identified
      as protective factor of mortality ([HR] 0.97, p = 0.048). The independent
      predictors associated with the echocardiographic response were absence of mitral
      insufficiency, presence of left bundle branch block and percentage of
      biventricular stimulation. CONCLUSION: Mortality in patients submitted to CRT in
      a tertiary hospital was independently associated with age, presence of COPD and
      previous AMI. The percentage of biventricular pacing evaluated 6 months after
      resynchronizer implantation was independently associated with improved survival
      and echocardiographic response.

PMID- 29185616
TI  - Incremental Prognostic Value of Conventional Echocardiography in Patients with
      Acutely Decompensated Heart Failure.
AB  - BACKGROUND: Acutely decompensated heart failure (ADHF) presents high morbidity
      and mortality in spite of therapeutic advance. Identifying factors of worst
      prognosis is important to improve assistance during the hospital phase and follow
      up after discharge. The use of echocardiography for diagnosis and therapeutic
      guidance has been of great utility in clinical practice. However, it is not clear
      if it could also be useful for risk determination and classification in patients
      with ADHF and if it is capable of adding prognostic value to a clinical score
      (OPTIMIZE-HF). OBJECTIVE: To identify the echocardiographic variables with
      independent prognostic value and to test their incremental value to a clinical
      score. METHODS: Prospective cohort of patients consecutively admitted between
      January 2013 and January 2015, with diagnosis of acutely decompensated heart
      failure, followed up to 60 days after discharge. Inclusion criteria were raised
      plasma level of NT-proBNP (> 450 pg/ml for patients under 50 years of age or NT
      proBNP > 900 pg/ml for patients over 50 years of age) and at least one of the
      signs and symptoms: dyspnea at rest, low cardiac output or signs of right-sided
      HF. The primary outcome was the composite of death and readmission for
      decompensated heart failure within 60 days. RESULTS: Study participants included
      110 individuals with average age of 68 +/- 16 years, 55% male. The most frequent
      causes of decompensation (51%) were transgression of the diet and irregular use
      of medication. Reduced ejection fraction (<40%) was present in 47% of cases, and
      the NT-proBNP median was 3947 (IIQ = 2370 to 7000). In multivariate analysis, out
      of the 16 echocardiographic variables studied, only pulmonary artery systolic
      pressure remained as an independent predictor, but it did not significantly
      increment the C-statistic of the OPTMIZE-HF score. CONCLUSION: The addition of
      echocardiographic variables to the OPTIMIZE-HF score, with the exception of left
      ventricular ejection fraction, did not improve its prognostic accuracy concerning
      cardiovascular events (death or readmission) within 60 days.

PMID- 29185618
TI  - POOR SCHOOL PERFORMANCE: IMPORTANCE OF CHILD SELF-REPORT.

PMID- 29185617
TI  - Percutaneous Intervention in ST-Elevation Myocardial Infarction: Culprit-only or
      Complete Revascularization?
AB  - The best approach of multivessel coronary artery disease in the context of acute
      myocardial infarction with ST segment elevation and primary percutaneous coronary
      intervention is one of the main reasons for controversy in cardiology. Although
      the main global guidelines do not recommend routine complete revascularization in
      these patients, recent randomized clinical trials have demonstrated benefit of
      this approach in reducing cardiovascular outcomes. For this reason, an adequate
      review of this evidence is essential in order to establish scientifically based
      strategy and achieve better outcomes for these patients who present with acute
      myocardial infarction. This review aims to present objectively the most recent
      evidence available on this topic.

PMID- 29185619
TI  - IN TIME: PUBLONS SEEKS TO ATTRACT REVIEWERS AND IMPROVE PEER REVIEW.

PMID- 29185620
TI  - USE OF SCORE AND CEREBROSPINAL FLUID LACTATE DOSAGE IN DIFFERENTIAL DIAGNOSIS OF
      BACTERIAL AND ASEPTIC MENINGITIS.
AB  - OBJECTIVE: To evaluate Bacterial Meningitis Score (BMS) on its own and in
      association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish
      bacterial from aseptic meningitis. METHODS: Children diagnosed with meningitis at
      a tertiary hospital between January/2011 and December/2014 were selected. All
      data were obtained upon admission. BMS was applied and included: CSF Gram
      staining (2 points); CSF neutrophil count >=1,000 cells/mm3 (1 point); CSF
      protein >=80 mg/dL (1 point); peripheral blood neutrophil count >=10,000
      cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for
      CSF lactate was >=30 mg/dL. Sensitivity, specificity and negative predictive
      value of several BMS cutoffs and BMS associated with high CSF lactate were
      evaluated for prediction of bacterial meningitis. RESULTS: Among 439 eligible
      patients, 94 did not have all data available to complete the score, and 345
      patients were included: 7 in bacterial meningitis group and 338 in aseptic
      meningitis group. As predictive factors of bacterial meningitis, BMS >=1 had 100%
      sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative
      predictive value (97.5-100); BMS >=2 or BMS >=1 associated with high CSF lactate
      also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and
      100% negative predictive value (98.3-100). CONCLUSIONS: 2 point BMS in
      association with CSF lactate dosage had the same sensitivity and negative
      predictive value, with increased specificity for diagnosis of bacterial
      meningitis when compared with 1-point BMS.

PMID- 29185621
TI  - THERAPEUTIC APPROACH AND ITS RELATIONSHIP WITH SOCIAL AND ECONOMIC
      CHARACTERISTICS OF USERS OF CENTERS FOR PSYCHOSOCIAL CARE FOR CHILDREN AND
      ADOLESCENTS.
AB  - OBJECTIVE: To analyze the therapeutic approach and its relationship with the
      economic and social characteristics and the care of children in Centers for
      Psychosocial Attention. METHODS: Descriptive study with a sample of 294 children
      monitored in two Centers for Psychosocial Attention to Children and Adolescents
      in Fortaleza, Ceara, Northeast Brazil. The study was conducted from February to
      December, 2012. Participants were accompanied by their parents or caregivers.
      Data were collected in a structured questionnaire containing social, economic and
      care variables. The bivariate analysis used the chi2 test to test the association
      between variables. RESULTS: In this study, 292 children aged 3-12 were selected,
      following the order of attendance at the service, most of them male (74.3%) and
      belonging to social classes D and E (89.3%). The most frequent diagnosis referred
      to by the caregivers was mental disorders. Three different therapeutic approaches
      were identified: pharmacological approach (44.5%); non-pharmacological approach
      (11.6%); association of both techniques (43.8%). For all therapeutic approaches,
      there was association with the variable living situation (p=0.021), as well as
      with the variables, "improving" with the treatment (p=0.002) and "problems" with
      the treatment (p=0,004). CONCLUSIONS: It was possible to highlight that the
      associated therapeutic approach (pharmacological and non-pharmacological
      treatment) provides more benefits to children. Therefore, associating the
      medicines to the psychotherapeutic practices may be recommended as a strategy in
      the mental health policy directed to children and adolescents.

PMID- 29185622
TI  - MILK CONSUMPTION IN INFANTS UNDER ONE YEAR OF AGE AND VARIABLES ASSOCIATED WITH
      NON-MATERNAL MILK CONSUMPTION.
AB  - OBJECTIVE: To verify the type of milk consumed by children under one year of age
      and identify variables associated with non-maternal milk consumption (formula or
      cow milk). METHODS: Cross-sectional study developed during the 2012 National
      Vaccination Campaign against Poliomyelitis. The companions of 935 children under
      one year of age answered a structured questionnaire on the child's diet in the
      last 24 hours. The estimates are presented by points, with 95%CI. F-statistics
      were used to check for differences in the proportion of the types of milk
      consumption according to the children's age range (<6 months and 6-11 months) and
      the association between non-maternal milk consumption and the study variables.
      RESULTS: The consumption of maternal milk and child formula was higher for
      children under six months of age - corresponding to 82.8% (95%CI 78.5-86.3) and
      70.4% (95%CI 61.4-78.0), respectively -, whereas the consumption of cow milk was
      higher among children between 6 and 11 months of age - 74.2% (95%CI 66.5-80.6) -,
      with differences in the consumption proportions (p<0.0001). The variables
      associated with higher cow milk consumption were lower maternal education
      (p<0.0001), the fact that the mother does not have a paid occupation (p=0.0015),
      child doctor's appointment in the public health network (p<0.0001) and
      participation in the Child's Milk Program (p<0.0001). CONCLUSIONS: The infants
      received cow's milk early (before the first year of life), especially children
      from families with lower socioeconomic levels and children who took part in a
      specific social program for milk distribuition.

PMID- 29185623
TI  - QUALITY OF LIFE AND HEALTH SELF-PERCEPTION IN CHILDREN WITH POOR SCHOOL
      PERFORMANCE.
AB  - OBJECTIVE: To examine the association between quality of life and health self
      perception of children with poor school performance, considering sociodemographic
      factors. METHODS: An analytical, observational, cross-sectional study was
      conducted with 99 children aged 7 to 12 years receiving specialized educational
      assistance. Parents and legal guardians answered questions concerning the
      sociodemographic profile. For an assessment of the quality of life and proposed
      domains (autonomy, functioning, leisure, and family), the children completed the
      Autoquestionnarie Qualite de Vie Enfant Image (AUQEI) and answered a question
      concerning their self-perceived health. Data were analyzed using multiple linear
      regression, considering a 5% significance level. RESULTS: Among the evaluated
      children, 69 (69.7%) male participants with mean age of 8.7+/-1.5, 27% self
      assessed their health status as poor/very poor, and 36.4% of the children
      reported having impaired quality of life. As for the domains assessed by AUQEI,
      there was statistical significance in the associations between family with age,
      autonomy with economic classification, and leisure and functioning with self
      perceived health. CONCLUSIONS: The quality of life of children with academic
      underachievement is associated with their health self-perception and
      sociodemographic characteristics.

PMID- 29185624
TI  - THE EFFECT OF ADAPTED SPORTS IN QUALITY OF LIFE AND BIOPSYCHOSOCIAL PROFILE OF
      CHILDREN AND ADOLESCENTS WITH CEREBRAL PALSY.
AB  - OBJECTIVE: The participation in sports and recreational activities promotes
      inclusion and the quality of life (QOL) for people with some type of disability.
      This study aims to evaluate and describe the effect of adapted sports (AS) on the
      QOL and biopsychosocial profile of children/adolescents with cerebral palsy (CP).
      METHODS: Forty-seven children/adolescents with CP were evaluated and referred to
      AS (soccer and swimming). The QOL was evaluated by the Pediatric Outcome Data
      Collection Instrument (PODCI) and the biopsychosocial profile by the Behavior
      Checklist for Children/Adolescents (CBCL). These instruments considered the
      influence of gender, age, race, social income, education and topography of
      spasticity. RESULTS: Seventeen children/adolescents who practiced AS were re
      evaluated after one year. There was significant improvement in the dimensions of
      transfers and mobility (p=0.009), upper extremity function (p=0.021) and global
      function (p=0.004) of IARRP. There was significant improvement considering the
      attention disorder syndrome (p=0.026), and the attention deficit hyperactivity
      disorders (p=0.008) in the Diagnostic and Statistical Manual of Mental Disorders
      (DSM)-oriented analysis (CBCL). Children/adolescents with diplegia obtained
      greater benefit than those with hemiplegia in relation to the comfort and pain
      (p=0.02) and global dimension (p=0.027) (PODCI). The boys had higher scores in
      total competence (p=0.048); the extremely poor group obtained higher levels in
      the breaking rules syndrome (p=0.008). CONCLUSIONS: The AS had a positive effect
      on the QOL and biopsychosocial profile of children/adolescents with CP in this
      sample, especially considering the global and upper extremity function, capacity
      for transfers and mobility, and benefits in the problems related to difficulties
      in attention.

PMID- 29185625
TI  - UNUSUAL WARFARIN DOSE TO ACHIEVE THERAPEUTIC INR IN A 4-MONTH OLD CHILD: NON
      GENETICS RISK FACTORS ARE STILL A CHALLENGE.
AB  - OBJECTIVE: To report a case of a 4-month old girl that required 0.7 mg/kg/day (5
      mg) of warfarin and discuss relevant risk factors for requiring higher doses.
      CASE DESCRIPTION: In November 2015, a 5 kg female infant (36-week preterm) was
      admitted to the hospital due to status epilepticus and fever. Diazepam, phenytoin
      and ceftriaxone were prescribed. Cerebrospinal fluid contained 7 leukocytes, 150
      mg/dL proteins, 1 mg/dL glucose and gram positive cocci were observed. Cranial
      tomography suggested hypodense signs in the cerebellum, right temporal lobe and
      left basal nuclei, which was consistent with pneumococcal meningitis-induced
      infectious vasculitis. She required low molecular weight heparin and warfarin for
      post-encephalitis thrombosis. About 10 days were required to achieve therapeutic
      INR, and warfarin was adjusted five times since the initial prescription.
      COMMENTS: The risk factors for higher warfarin doses were age and enteral tube
      feeding. Phenobarbital and prednisone might also have contributed with one of the
      highest warfarin dose ever reported. Despite current importance given to genetics
      testing, clinicians should attempt to identify common contributing factors for
      prolonged non-therapeutic INR, to minimize the risk of coagulation, and to reduce
      costs of hospital stay and laboratory exams.

PMID- 29185626
TI  - Do resources buffer the prospective association of psychosocial work stress with
      depression? Longitudinal evidence from ageing workers.
AB  - Objectives There is now convincing evidence that psychosocial work stressors are
      linked to depression. Few studies, however, have tested if individual resources
      can buffer the longitudinal effects of psychosocial work stressors on depressive
      symptoms. This study investigates how two types of resources (internal and
      external resources) affect the association between psychosocial work stressors
      and depressive symptoms. Methods Data were obtained from the US Health and
      Retirement Study, with baseline information on psychosocial work stressors [job
      strain and effort-reward imbalance (ERI)] and on internal ("high mastery" and
      "low constraints") and external resources ("private social support") among
      initially healthy workers. This information was linked to elevated depressive
      symptoms two years later. The sample includes 5473 observations and we report
      relative risks (RR) and effect modification on the additive and multiplicative
      scale. Results Psychosocial stressors and low resources (internal and external)
      were both independently related to depressive symptoms. Individuals with both,
      psychosocial stressors and low resources, had the highest risk of developing
      elevated depressive symptoms (eg, RR ERI-LowMastery3.32, 95% CI 2.49-4.42; RR
      JobStrain-LowMastery2.89, 95% CI 2.18-3.84). Yet, based on interaction analyses,
      only social support from friends buffered the association between work stressors
      and depressive symptoms. Conclusions Our findings have demonstrated that
      psychosocial stressors at work are related to mental health, and that in most
      cases this relationship holds true both for people with high and with low
      resources. Therefore, there is no clear indication that internal or external
      resources buffer the association between psychosocial work stressors and
      depressive symptoms.

PMID- 29185628
TI  - ?

PMID- 29185627
TI  - Strategies for enhancing the implementation of school-based policies or practices
      targeting risk factors for chronic disease.
AB  - BACKGROUND: A number of school-based policies or practices have been found to be
      effective in improving child diet and physical activity, and preventing excessive
      weight gain, tobacco or harmful alcohol use. Schools, however, frequently fail to
      implement such evidence-based interventions. OBJECTIVES: The primary aims of the
      review are to examine the effectiveness of strategies aiming to improve the
      implementation of school-based policies, programs or practices to address child
      diet, physical activity, obesity, tobacco or alcohol use.Secondary objectives of
      the review are to: Examine the effectiveness of implementation strategies on
      health behaviour (e.g. fruit and vegetable consumption) and anthropometric
      outcomes (e.g. BMI, weight); describe the impact of such strategies on the
      knowledge, skills or attitudes of school staff involved in implementing health
      promoting policies, programs or practices; describe the cost or cost
      effectiveness of such strategies; and describe any unintended adverse effects of
      strategies on schools, school staff or children. SEARCH METHODS: All electronic
      databases were searched on 16 July 2017 for studies published up to 31 August
      2016. We searched the following electronic databases: Cochrane Library including
      the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; MEDLINE In
      Process & Other Non-Indexed Citations; Embase Classic and Embase; PsycINFO;
      Education Resource Information Center (ERIC); Cumulative Index to Nursing and
      Allied Health Literature (CINAHL); Dissertations and Theses; and SCOPUS. We
      screened reference lists of all included trials for citations of other
      potentially relevant trials. We handsearched all publications between 2011 and
      2016 in two specialty journals (Implementation Science and Journal of
      Translational Behavioral Medicine) and conducted searches of the WHO
      International Clinical Trials Registry Platform (ICTRP)
      (http://apps.who.int/trialsearch/) as well as the US National Institutes of
      Health registry (https://clinicaltrials.gov). We consulted with experts in the
      field to identify other relevant research. SELECTION CRITERIA: 'Implementation'
      was defined as the use of strategies to adopt and integrate evidence-based health
      interventions and to change practice patterns within specific settings. We
      included any trial (randomised or non-randomised) conducted at any scale, with a
      parallel control group that compared a strategy to implement policies or
      practices to address diet, physical activity, overweight or obesity, tobacco or
      alcohol use by school staff to 'no intervention', 'usual' practice or a different
      implementation strategy. DATA COLLECTION AND ANALYSIS: Citation screening, data
      extraction and assessment of risk of bias was performed by review authors in
      pairs. Disagreements between review authors were resolved via consensus, or if
      required, by a third author. Considerable trial heterogeneity precluded meta
      analysis. We narratively synthesised trial findings by describing the effect size
      of the primary outcome measure for policy or practice implementation (or the
      median of such measures where a single primary outcome was not stated). MAIN
      RESULTS: We included 27 trials, 18 of which were conducted in the USA. Nineteen
      studies employed randomised controlled trial (RCT) designs. Fifteen trials tested
      strategies to implement healthy eating policies, practice or programs; six trials
      tested strategies targeting physical activity policies or practices; and three
      trials targeted tobacco policies or practices. Three trials targeted a
      combination of risk factors. None of the included trials sought to increase the
      implementation of interventions to delay initiation or reduce the consumption of
      alcohol. All trials examined multi-strategic implementation strategies and no two
      trials examined the same combinations of implementation strategies. The most
      common implementation strategies included educational materials, educational
      outreach and educational meetings. For all outcomes, the overall quality of
      evidence was very low and the risk of bias was high for the majority of trials
      for detection and performance bias.Among 13 trials reporting dichotomous
      implementation outcomes-the proportion of schools or school staff (e.g. classes)
      implementing a targeted policy or practice-the median unadjusted (improvement)
      effect sizes ranged from 8.5% to 66.6%. Of seven trials reporting the percentage
      of a practice, program or policy that had been implemented, the median unadjusted
      effect (improvement), relative to the control ranged from -8% to 43%. The effect,
      relative to control, reported in two trials assessing the impact of
      implementation strategies on the time per week teachers spent delivering targeted
      policies or practices ranged from 26.6 to 54.9 minutes per week. Among trials
      reporting other continuous implementation outcomes, findings were mixed. Four
      trials were conducted of strategies that sought to achieve implementation 'at
      scale', that is, across samples of at least 50 schools, of which improvements in
      implementation were reported in three trials.The impact of interventions on
      student health behaviour or weight status were mixed. Three of the eight trials
      with physical activity outcomes reported no significant improvements. Two trials
      reported reductions in tobacco use among intervention relative to control. Seven
      of nine trials reported no between-group differences on student overweight,
      obesity or adiposity. Positive improvements in child dietary intake were
      generally reported among trials reporting these outcomes. Three trials assessed
      the impact of implementation strategies on the attitudes of school staff and
      found mixed effects. Two trials specified in the study methods an assessment of
      potential unintended adverse effects, of which, they reported none. One trial
      reported implementation support did not significantly increase school revenue or
      expenses and another, conducted a formal economic evaluation, reporting the
      intervention to be cost-effective. Trial heterogeneity, and the lack of
      consistent terminology describing implementation strategies, were important
      limitations of the review. AUTHORS' CONCLUSIONS: Given the very low quality of
      the available evidence, it is uncertain whether the strategies tested improve
      implementation of the targeted school-based policies or practices, student health
      behaviours, or the knowledge or attitudes of school staff. It is also uncertain
      if strategies to improve implementation are cost-effective or if they result in
      unintended adverse consequences. Further research is required to guide efforts to
      facilitate the translation of evidence into practice in this setting.

PMID- 29185629
TI  - [Medical treatment of micturition problems in men : what the general practitioner
      needs to know].
AB  - Considering the high prevalence of lower urinary tract symptoms in men, and owing
      to the development of a better focused pharmacotherapy, general practitioners
      (GPs) have been already for a decade first in line to prescribe an initial
      medication. With the intent to improve this shared care, we give an overview of
      the two main syndromes, obstructive and irritative, and their medication, in
      order to reinforce knowledge transfer and optimize coordination between GPs and
      urologists.

PMID- 29185630
TI  - [Immunotherapy : a revolution in the management of urothelial bladder cancer ?]
AB  - The treatment of urothelial bladder cancer has changed very little in recent
      years, with high rates of disease recurrence and progression, even in low
      aggressive urothelial bladder cancer. Immunotherapy has already proven its
      effectiveness as a treatment for several types of cancer and has been used in
      high-grade non-muscle-invasive bladder cancer for decades. Recent findings on
      immune checkpoints inhibitors have opened up a new chapter for treatment of
      bladder cancer, offering interesting therapeutic perspectives that could
      revolutionize the management.

PMID- 29185631
TI  - [Myths and reality about immunonutrition in uro-oncology].
AB  - Postoperative morbidity remains a nightmare (although vivid), both for the
      patient and the surgeon. One phantasmagorical idea would be to give the patient a
      " magic potion " preoperatively aiming at eliminating the risk of postoperative
      complication. The purpose of the present review is to summarize the current
      knowledge on the potential benefits of immunonutrition administered to urological
      cancers patients. After a brief summary on the role of immunity in cancer
      surveillance and treatment, the rationale about administrating oral nutritional
      supplements able to modulate the patient's immune system before cystectomy for
      bladder cancer will be highlighted.

PMID- 29185632
TI  - [Local treatment in oligometastatic urological malignancies : evidence of wishful
      thinking ?]
AB  - In the past, it was generally considered that the window of curability had been
      missed in metastatic solid cancers. At present, novel evidence suggests that
      oligometastatic cancer might be amenable to a multimodal curative treatment,
      including ablation of the primary tumour. In this article, we summarise the
      indications, the controversies and future perspectives of local treatment in
      oligometastatic urological malignancies.

PMID- 29185633
TI  - [Intravesical microwave thermo-chemotherapy for the treatment of non-invasive
      bladder cancer].
AB  - Non-invasive urothelial carcinoma of the bladder is known for its significant
      rate of recurrence after transurethral resection (TURB) even after adjuvant
      intravesical chemotherapy or immunoprophylaxis. Therefore, new and more effective
      approaches for the management of non-invasive bladder tumors have been developed
      and are progressively introduced in clinical practice. Recently, the endovesical
      administration of a combined regimen using a cytostatic agent and microwave
      induced hyperthermia appears to be highly efficient and possibly superior to
      intravesical chemotherapy alone for none invasive bladder cancer.

PMID- 29185634
TI  - [Laparoscopic cystectomy-urinary diversion with robotic assistance : which future
      ?]
AB  - Known for its significant morbidity, radical cystectomy must improve minimally
      invasively. Rapidly but sporadically initiated at the beginning of the robotic
      era 15 years ago, laparoscopic cystectomy-urinary diversion has slowly progressed
      technically. It is actually optimally standardized to be entirely performed intra
      corporealy. Its technical difficulty remaining high, robotic cystectomy should
      remain in expert hands with a significant recruitement to remain performant.

PMID- 29185635
TI  - ?

PMID- 29185636
TI  - ?

PMID- 29185637
TI  - ?

PMID- 29185638
TI  - ?

PMID- 29185639
TI  - ?

PMID- 29185640
TI  - Ambulatory and short-burst oxygen for interstitial lung disease.
AB  - STATEMENT: The mission of the Cochrane Nursing Care Field (CNCF) is to improve
      health outcomes through increasing the use of the Cochrane Library and supporting
      Cochrane's role by providing an evidence base for nurses and healthcare
      professionals who deliver, lead or research nursing care. The CNCF produces
      Cochrane Corner columns, summaries of recent nursing-care-relevant Cochrane
      Reviews that are regularly published in collaborating nursing-related journals.
      Information on the processes CNCF has developed can be accessed at:
      cncf.cochrane.org/evidence-transfer-program-review-summaries. This is a Cochrane
      review summary of: Sharp C, Adamali H, Millar AB ( 2016 ) Ambulatory and short
      burst oxygen for interstitial lung disease. Cochrane Database of Systematic
      Reviews. Issue 6. CD011716. doi: 10.1002/14651858.CD011716.pub2.

PMID- 29185641
TI  - Development and regulation of advanced nurse practitioners in the UK and
      internationally.
AB  - The NHS in the UK is under increasing pressure as a result of financial and
      recruitment issues, as well as an ageing population. Nursing has continued to
      adapt to this challenging time. Over the past few years, the advanced nurse
      practitioner (ANP) role has been implemented widely in primary and secondary
      care. However, the ANP role has lacked consistency in scope of practice, training
      and regulation. This article summarises the development of the ANP role in the UK
      and internationally, and issues relating to regulation. Globally, ANPs are
      regulated by one of three different bodies: nationally by central government or a
      professional body, or locally by employers. In the UK, the role is regulated by
      local procedures, relying on employers to make decisions about the scope and
      preparation for practice. Some of the challenges in the UK in relation to ANP
      regulation are discussed, including variations in scope, organisational
      constraints and lack of support. These challenges are exacerbated by a lack of
      role clarity, thereby indicating there is a need to improve regulation of ANPs.
      The Royal College of Nursing has responded to these challenges by introducing
      'credentialing', a system for recording qualifications, skills and experience,
      but the uptake of this process is yet to be evaluated. Therefore, employers and
      ANPs should be aware of their collective responsibility for ensuring appropriate
      role regulation.

PMID- 29185642
TI  - Using the ABCDE approach to assess the deteriorating patient.
AB  - Patients who deteriorate without recognition or timely interventions are at risk
      of critical care admission and increased morbidity or mortality. This article
      outlines the systematic ABCDE (airway, breathing, circulation, disability,
      exposure) approach to patient assessment, which enables healthcare practitioners
      to identify and respond to life-threatening conditions in order of priority. The
      patient's vital signs should be measured as part of the ABCDE assessment and
      recorded using a track and trigger tool to enhance recognition of physiological
      abnormalities that signal deterioration. To optimise communication and escalation
      of deteriorating patients, healthcare practitioners should report ABCDE
      assessment findings using a structured communication tool.

PMID- 29185643
TI  - Effects of insulin intervention on the expression of VE-cadherin, beta-catenin,
      Annexin A2, Annexin A5, and 14-3-3 protein in the placentas of patients with
      gestational diabetes.

PMID- 29185644
TI  - Management of a Nontreatable Mandibular Anterior Tooth.

PMID- 29185645
TI  - The Lazarus Bone Graft: Revitalizing Allogenic Bone Blocks.

PMID- 29185646
TI  - Does Anatomy Matter? Having the Tenacity to Solve Complex Challenges.

PMID- 29185647
TI  - Shade-Matching Challenge: A Single Central Incisor.

PMID- 29185649
TI  - Hats Off to Our Leaders.

PMID- 29185648
TI  - Treating the Amelogenesis Imperfecta Patient .

PMID- 29185650
TI  - Clean Out the Closet!

PMID- 29185651
TI  - Pick Up the Pieces.

PMID- 29185652
TI  - Guided Implant Surgical Applications.

PMID- 29185653
TI  - Dual CBCT Scanning Technique for Completely Edentulous Arches.

PMID- 29185654
TI  - Should General Practitioners Place Implants?

PMID- 29185655
TI  - Single Versus Multiple Endodontic File Use.

PMID- 29185656
TI  - Modern Posterior Composite Placement: An Innovative Single-Increment Technique.

PMID- 29185657
TI  - Universal-Size Mouthguards: An Affordable Alternative for the Young Athlete.

PMID- 29185658
TI  - The Importance of Vital Signs.

PMID- 29185659
TI  - Beyond reducing fire hazard: fuel treatment impacts on overstory tree survival.
AB  - Fuel treatment implementation in dry forest types throughout the western
      UnitedStates is likely to increase in pace and scale in response to increasing
      incidence of large wildfires.While it is clear that properly implemented fuel
      treatments are effective at reducing hazardousfire potential, there are ancillary
      ecological effects that can impact forest resilience eitherpositively or
      negatively depending on the specific elements examined, as well as treatment
      type,timing, and intensity. In this study, we use overstory tree growth
      responses, measured sevenyears after the most common fuel treatments, to estimate
      forest health. Across the five speciesanalyzed, observed mortality and future
      vulnerability were consistently low in the mechanical-only treatment. Fire-only
      was similar to the control for all species except Douglas-fir, whilemechanical
      plus-fire had high observed mortality and future vulnerability for white fir and
      sugarpine. Given that overstory trees largely dictate the function of forests and
      services they provide(e.g., wildlife habitat, carbon sequestration, soil
      stability) these results have implications forunderstanding longer-term impacts
      of common fuel treatments on forest resilience.

PMID- 29185660
TI  - Are biological communities in naturally unproductive streams resistant to
      additional anthropogenic stressors?
AB  - Studies on the interactive responses to multiple simultaneously acting stressors
      have focused on individual or population-level responses in laboratory
      microcosms, while field-based studies on community-level responses are rare. We
      examined the influence of a natural (non-anthropogenic acidity) vs. human-induced
      stress (land drainage) and their interaction on species richness and spatial
      turnover (beta diversity) of stream diatom, bryophyte, and benthic invertebrate
      communities. Our four stream categories were: circumneutral reference,
      circumneutral impacted, naturally acidic, and naturally acidic impacted streams.
      We expected the most sensitive species to be present only in the circumneutral
      reference streams. Therefore, species richness should be highest in these streams
      and lowest in the naturally acidic streams additionally stressed by forest
      drainage. Alternatively, communities in acidic streams may consist of the most
      tolerant taxa that are unaffected by further stressors, species richness in these
      streams remaining unaffected by drainage. We also expected spatial turnover to be
      highest in the circumneutral near-pristine streams and lowest in the drainage
      impacted acidic streams. In all three taxonomic groups, alpha diversity was lower
      in the naturally acidic than in circumneutral streams. The additional impact of
      the anthropogenic stress on species richness varied between groups, having no
      effect on diatoms, antagonistic effect on bryophytes, and additive effect on
      invertebrates. We also found differences in how each stressor modified beta
      diversity of each taxonomic group. For diatoms, beta diversity showed an overall
      tendency to decrease with increasing stress level, while bryophyte beta diversity
      responded mainly to forest drainage. Benthic invertebrate beta diversity did not
      differ between treatments. Our results suggest that non-additive effects among
      stressors need special attention to improve the understanding and management of
      multifactor responses in streams. Our results also argue for the primacy of a
      multi-taxon approach to environmental impact detection, and for the inclusion of
      a wide array of ecological responses, particularly community turnover, in
      bioassessment programs to detect responses that may go unnoticed by conventional
      richness-based measures.

PMID- 29185661
TI  - Is U.S. climatic diversity well represented within the existing federal
      protection network?
AB  - Establishing protection networks to ensure that biodiversity and associated
      ecosystem services persist under changing environments is a major challenge for
      conservation planning. The potential consequences of altered climates for the
      structure and function of ecosystems necessitates new and complementary
      approaches be incorporated into traditional conservation plans. The conterminous
      United States of America (CONUS) has an extensive system of protected areas
      managed by federal agencies, but a comprehensive assessment of how this network
      represents CONUS climate is lacking. We present a quantitative classification of
      the climate space that is independent from the geographic locations to evaluate
      the climatic representation of the existing protected area network. We use this
      classification to evaluate the coverage of each agency's jurisdiction and to
      identify current conservation deficits. Our findings reveal that the existing
      network poorly represents CONUS climatic diversity. Although rare climates are
      generally well represented by the network, the most common climates are
      particularly underrepresented. Overall, 83% of the area of the CONUS corresponds
      to climates underrepresented by the network. The addition of some currently
      unprotected federal lands to the network would enhance the coverage of CONUS
      climates. However, to fully palliate current conservation deficits, large-scale
      private-land conservation initiatives will be critical.

PMID- 29185662
TI  - Dry forest resilience varies under simulated climate-management scenarios in a
      central Oregon, USA landscape.
AB  - Determining appropriate actions to create or maintain landscapes resilient to
      climate change is challenging because of uncertainty associated with potential
      effects of climate change and their interactions with land management. We used a
      set of climate-informed state-and-transition models to explore the effects of
      management and natural disturbances on vegetation composition and structure under
      different future climates. Models were run for dry forests of central Oregon
      under a fire suppression scenario (i.e., no management other than the continued
      suppression of wildfires) and an active management scenario characterized by
      light to moderate thinning from below and some prescribed fire, planting, and
      salvage logging. Without climate change, area in dry province forest types
      remained constant. With climate change, dry mixed-conifer forests increased in
      area (by an average of 21-26% by 2100), and moist mixed-conifer forests decreased
      in area (by an average of 36-60% by 2100), under both management scenarios.
      Average area in dry mixed-conifer forests varied little by management scenario,
      but potential decreases in the moist mixed-conifer forest were lower with active
      management. With changing climate in the dry province of central Oregon, our
      results suggest the likelihood of sustaining current levels of dense, moist mixed
      conifer forests with large-diameter, old trees is low (less than a 10% chance)
      irrespective of management scenario; an opposite trend was observed under no
      climate change simulations. However, results also suggest active management
      within the dry and moist mixed-conifer forests that creates less dense forest
      conditions can increase the persistence of larger-diameter, older trees across
      the landscape. Owing to projected increases in wildfire, our results also suggest
      future distributions of tree structures will differ from the present. Overall,
      our projections indicate proactive management can increase forest resilience and
      sustain some societal values, particularly in drier forest types. However,
      opportunities to create more disturbance-adapted systems are finite, all values
      likely cannot be sustained at current levels, and levels of resilience success
      will likely vary by dry province forest type. Land managers planning for a future
      without climate change may be assuming a future that is unlikely to exist.

PMID- 29185663
TI  - Effects of climate and nutrient load on the water quality of shallow lakes
      assessed through ensemble runs by PCLake.
AB  - Complex ecological models are used to predict the consequences of anticipated
      future changes in climate and nutrient loading for lake water quality. These
      models may, however, suffer from nonuniqueness in that various sets of model
      parameter values may yield equally satisfactory representations of the system
      being modeled, but when applied in future scenarios these sets of values may
      divert considerably in their simulated outcomes. Compilation of an ensemble of
      model runs allows us to account for simulation variability arising from model
      parameter estimates. Thus, we propose a new approach for aquatic ecological
      models creating a more robust prediction of future water quality. We used our
      ensemble approach in an application of the widely used PCLake model for Danish
      shallow Lake Arreskov, which during the past two decades has demonstrated
      frequent shifts between turbid and clear water states. Despite marked
      variability, the span of our ensemble runs encapsulated 70-90% of the observed
      variation in lake water quality. The model exercise demonstrates that future
      warming and increased nutrient loading lead to lower probability of a clear
      water, vegetation-rich state and greater likelihood of cyanobacteria dominance.
      In a 6.0 degrees C warming scenario, for instance, the current nutrient loading
      of nitrogen and phosphorus must be reduced by about 75% to maintain the present
      ecological state of Lake Arreskov, but even in a near-future 2.0 degrees C
      warming scenario, a higher probability of a turbid, cyanobacteria-dominated state
      is predicted. As managers may wish to determine the probability of achieving a
      certain ecological state, our proposed ensemble approach facilitates new ways of
      communicating future stressor impacts.

PMID- 29185665
TI  - Groundwater availability mediates the ecosystem effects of an invasion of
      Prosopis pallida.
AB  - Groundwater levels in arid environments are dropping worldwide due to human
      extraction, and precipitation events are predicted to become rarer and more
      intense in many arid areas with global climate change. These changes will likely
      alter both primary productivity and plant-soil nutrient cycles. To better
      understand the nature of such alterations, we examined effects of groundwater
      availability on plant-soil nitrogen (N) cycling in areas invaded by the N-fixing
      phreatophyte, Prosopis pallida, on the dry leeward coast of Hawai'i Island. Our
      aims were to quantify effects of groundwater availability to P. pallida on rates
      of litterfall N inputs and accretion in soils and to quantify effects of
      groundwater availability on N mineralization and leaching rates of inorganic N
      under natural rainfall conditions and simulated rain events. Stem water delta18O
      values indicate that P. pallida trees in lowland plots accessed shallow
      groundwater, while in upland plots they relied solely on rainfall. During drought
      periods, P. pallida at upland plots experienced water stress, evidenced by lower
      stem water potentials, higher water-use efficiency, and lower predawn
      photosynthetic performance than at lowland plots. Prosopis pallida basal area was
      5.3 times greater at lowland plots, and these plots exhibited 17 times higher
      carbon (C), 24 times higher N, and 35 times higher phosphorus (P) additions via
      litterfall, indicating that productivity of this phreatophyte was decoupled from
      rainfall where groundwater was present. Total N mass in soils was 4.7 times
      greater where groundwater was accessible, supporting the case that groundwater
      access increased N2 fixation at a stand level. In contrast, N mineralization and
      leaching losses from soils, though substantially greater in lowland relative to
      upland areas, were strongly controlled by rainfall. Results provide clear
      examples of how invasive species with particular functional attributes (i.e., N
      fixing phreatophytes) exploit otherwise inaccessible resources to dramatically
      alter the functioning of the systems they invade and how anthropogenic changes to
      hydrological processes can also alter ecosystem-level impacts of biological
      invasions. Results also illustrate a mechanism by which regional groundwater
      drawdown may reduce soil nutrient accretion and availability in arid regions.

PMID- 29185664
TI  - Agrochemicals indirectly increase survival of E. coli O157:H7 and indicator
      bacteria by reducing ecosystem services.
AB  - Storm water and agricultural runoff frequently contain agrochemicals, fecal
      indicator bacteria (FIB), and zoonotic pathogens. Entry of such contaminants into
      aquatic ecosystems may affect ecology and human health. This study tested the
      hypothesis that the herbicide atrazine and the fungicide chlorothalonil
      indirectly affect the survival of FIB (Escherichia coli and Enterococcus
      faecalis) and a pathogen (E. coli O157:H7) by altering densities of protozoan
      predators or by altering competition from autochthonous bacteria. Streptomycin
      resistant E. coli, En. faecalis, and E. coli O157:H7 were added to microcosms
      composed of Florida river water containing natural protozoan and bacterial
      populations. FIB, pathogen, and protozoan densities were monitored over six days.
      Known metabolic inhibitors, cycloheximide and streptomycin, were used to inhibit
      autochthonous protozoa or bacteria, respectively. The inhibitors made it possible
      to isolate the effects of predation or competition on survival of allochthonous
      bacteria, and each treatment increased the survival of FIB and pathogens.
      Chlorothalonil's effect was similar to that of cycloheximide, significantly
      reducing protozoan densities and elevating densities of FIB and pathogens
      relative to the control. Atrazine treatment did not affect protozoan densities,
      but, through an effect on competition, resulted in significantly greater
      densities of En. faecalis and E. coli O157:H7. Hence, by reducing predaceous
      protozoa and bacterial competitors that facilitate purifying water bodies of FIBs
      and human pathogens, chlorothalonil and atrazine indirectly diminished an
      ecosystem service of fresh water.

PMID- 29185666
TI  - Limitations of extrapolating toxic effects on reproduction to the population
      level.
AB  - For the ecological risk assessment of toxic chemicals, standardized tests on
      individuals are often used as proxies for population-level effects. Here, we
      address the utility of one commonly used metric, reproductive output, as a proxy
      for population-level effects. Because reproduction integrates the outcome of many
      interacting processes (e.g., feeding, growth, allocation of energy to
      reproduction), the observed toxic effects in a reproduction test could be due to
      stress on one of many processes. Although this makes reproduction a robust
      endpoint for detecting stress, it may mask important population-level
      consequences if the different physiological processes stress affects are
      associated with different feedback mechanisms at the population level. We
      therefore evaluated how an observed reduction in reproduction found in a standard
      reproduction test translates to effects at the population level if it is caused
      by hypothetical toxicants affecting different physiological processes
      (physiological modes of action; PMoA). For this we used two consumer-resource
      models: the Yodzis-Innes (YI) model, which is mathematically tractable, but
      requires strong assumptions of energetic equivalence among individuals as they
      progress through ontogeny, and an individual-based implementation of dynamic
      energy budget theory (DEB-IBM), which relaxes these assumptions at the expense of
      tractability. We identified two important feedback mechanisms controlling the
      link between individual- and population-level stress in the YI model. These
      mechanisms turned out to also be important for interpreting some of the
      individual-based model results; for two PMoAs, they determined the population
      response to stress in both models. In contrast, others stress types involved more
      complex feedbacks, because they asymmetrically stressed the production efficiency
      of reproduction and somatic growth. The feedbacks associated with different PMoAs
      drastically altered the link between individual- and population-level effects.
      For example, hypothetical stressors with different PMoAs that had equal effects
      on reproduction had effects ranging from a negligible decline in biomass to
      population extinction. Thus, reproduction tests alone are of little use for
      extrapolating toxicity to the population level, but we showed that the ecological
      relevance of standard tests could easily be improved if growth is measured along
      with reproduction.

PMID- 29185667
TI  - Aboveground biomass mapping of African forest mosaics using canopy texture
      analysis: toward a regional approach.
AB  - In the context of the reduction of greenhouse gas emissions caused by
      deforestation and forest degradation (the REDD+ program), optical very high
      resolution (VHR) satellite images provide an opportunity to characterize forest
      canopy structure and to quantify aboveground biomass (AGB) at less expense than
      methods based on airborne remote sensing data. Among the methods for processing
      these VHR images, Fourier textural ordination (FOTO) presents a good method to
      detect forest canopy structural heterogeneity and therefore to predict AGB
      variations. Notably, the method does not saturate at intermediate AGB values as
      do pixelwise processing of available space borne optical and radar signals.
      However, a regional-scale application requires overcoming two difficulties: (1)
      instrumental effects due to variations in sun-scene-sensor geometry or sensor
      specific responses that preclude the use of wide arrays of images acquired under
      heterogeneous conditions and (2) forest structural diversity including
      monodominant or open canopy forests, which are of particular importance in
      Central Africa. In this study, we demonstrate the feasibility of a rigorous
      regional study of canopy texture by harmonizing FOTO indices of images acquired
      from two different sensors (Geoeye-1 and QuickBird-2) and different sun-scene
      sensor geometries and by calibrating a piecewise biomass inversion model using 26
      inventory plots (1 ha) sampled across very heterogeneous forest types. A good
      agreement was found between observed and predicted AGB (residual standard error
      [RSE] = 15%; R2 = 0.85; P < 0.001) across a wide range of AGB levels from 26
      Mg/ha to 460 Mg/ha, and was confirmed by cross validation. A high-resolution
      biomass map (100-m pixels) was produced for a 400-km2 area, and predictions
      obtained from both imagery sources were consistent with each other (r = 0.86;
      slope = 1.03; intercept = 12.01 Mg/ha). These results highlight the horizontal
      structure of forest canopy as a powerful descriptor of the entire forest stand
      structure and heterogeneity. In particular, we show that quantitative metrics
      resulting from such textural analysis offer new opportunities to characterize the
      spatial and temporal variation of the structure of dense forests and may
      complement the toolbox used by tropical forest ecologists, managers or REDD+
      national monitoring, reporting and verification bodies.

PMID- 29185668
TI  - Long-term monitoring reveals differing impacts of elephants on elements of a
      canopy shrub community.
AB  - The conservation management of southern Africa's elephants focuses on identifying
      and mitigating the extent and intensity of impacts on biological diversity.
      However, variation in the intensity of elephant effects between elements of
      biodiversity is seldom explored, which limits our ability to interpret the scale
      of the impacts. Our study quantifies >50 years of impacts in the succulent
      thickets of the Addo Elephant National Park, South Africa, contrasting hypotheses
      for the resilience of the canopy shrubs (a key functional guild) to elephants
      with those that argue the opposite. We also assess the impacts between elements
      of the community, ranging from community composition and structure to the
      structure of individual canopy species. We show the vulnerability of the canopy
      shrubs to transformation as the accumulated influences of elephants alter
      community composition and structure. The pattern of transformation is similar to
      that caused by domestic herbivores, which leads us to predict that elephants will
      eventually bring about landscape-level degradation and a significant loss of
      biodiversity. While we expected the canopy species to show similar declining
      trends in structure, providing insight into the response of the community as a
      whole, we demonstrate an uneven distribution of impacts between constituent
      elements; most of the canopy dominants exhibited little change, resisting
      removal. This implies that these canopy dominants might not be useful indicators
      of community change in thickets, a pattern that is likely repeated among the
      canopy trees of savanna systems. Our findings suggest that predicting elephant
      impacts, and finding solutions to the so-called "elephant problem," require a
      broader and more integrated understanding of the mechanisms driving the changes
      between elements of biodiversity at various spatial and temporal scales.

PMID- 29185669
TI  - Habitat- and rainfall-dependent biodiversity responses to cattle removal in an
      arid woodland-grassland environment.
AB  - Biodiversity conservation in rangeland environments is often addressed by
      removing livestock, but inconsistent responses by biota mean that the efficacy of
      this form of management is hotly debated. Reasons for this inconsistency include
      the usually short duration and small spatial scale of manipulations compared to
      the area of grazing properties, as well as divergent responses amongst biota. In
      low-productivity arid environments, the pulse-reserve dynamic also complicates
      the outcome of manipulations. Here, we tested and extended these ideas in a
      heterogeneous desert environment in central Australia that consists of small
      patches of open woodland (gidgee) in a grassland (spinifex) matrix. Taking
      advantage of a controlled property-scale removal of cattle, and a rain event that
      stimulated productivity, we first quantified differences in the vegetation and
      small vertebrates of these two habitats, and then tracked the diversity,
      composition, and abundance of these biota for 6-19 months post-rain. We predicted
      that the two habitats would differ in the structure, composition, and
      reproductive output of their constituent plant species. We predicted also that
      the effects of cattle removal would interact with these habitat differences, with
      the abundance, richness, and diversity of small mammals and reptiles differing
      across habitats and grazing treatments. As anticipated, plant species composition
      in woodland was distinct from that in grassland and varied over time. The effects
      of cattle removal were habitat specific: Plant composition responded to de
      stocking in woodland, but not in grassland; flowers were more abundant, and
      palatable plant cover also was greater following cessation of grazing pressure.
      The responses of small mammals but not reptiles showed some accord with our
      predictions, varying over time but inconsistently with treatment, and perhaps
      reflected high variability in capture success. We conclude that the timing and
      length of sampling are important when evaluating the responses of biota to
      livestock removal, as is the inclusion of all key habitats in the sampling
      regime.

PMID- 29185670
TI  - Selective-logging and oil palm: multitaxon impacts, biodiversity indicators, and
      trade-offs for conservation planning.
AB  - Strong global demand for tropical timber and agricultural products has driven
      large-scale logging and subsequent conversion of tropical forests. Given that the
      majority of tropical landscapes have been or will likely be logged, the
      protection of biodiversity within tropical forests thus depends on whether
      species can persist in these economically exploited lands, and if species cannot
      persist, whether we can protect enough primary forest from logging and
      conversion. However, our knowledge of the impact of logging and conversion on
      biodiversity is limited to a few taxa, often sampled in different locations with
      complex land-use histories, hampering attempts to plan cost-effective
      conservation strategies and to draw conclusions across taxa. Spanning a land-use
      gradient of primary forest, once- and twice-logged forests, and oil palm
      plantations, we used traditional sampling and DNA metabarcoding to compile an
      extensive data set in Sabah, Malaysian Borneo for nine vertebrate and
      invertebrate taxa to quantify the biological impacts of logging and oil palm,
      develop cost-effective methods of protecting biodiversity, and examine whether
      there is congruence in response among taxa. Logged forests retained high species
      richness, including, on average, 70% of species found in primary forest. In
      contrast, conversion to oil palm dramatically reduces species richness, with
      significantly fewer primary-forest species than found on logged forest transects
      for seven taxa. Using a systematic conservation planning analysis, we show that
      efficient protection of primary-forest species is achieved with land portfolios
      that include a large proportion of logged-forest plots. Protecting logged forests
      is thus a cost-effective method of protecting an ecologically and taxonomically
      diverse range of species, particularly when conservation budgets are limited. Six
      indicator groups (birds, leaf-litter ants, beetles, aerial hymenopterans, flies,
      and true bugs) proved to be consistently good predictors of the response of the
      other taxa to logging and oil palm. Our results confidently establish the high
      conservation value of logged forests and the low value of oil palm. Cross-taxon
      congruence in responses to disturbance also suggests that the practice of
      focusing on key indicator taxa yields important information of general
      biodiversity in studies of logging and oil palm.

PMID- 29185672
TI  - Diagnosis and management of group A streptococcal pharyngitis and associated
      complications
AB  - Although group A Streptococcus (GAS) pharyngitis is the most common cause of
      bacterial pharyngitis in children and adolescents, many viral and bacterial
      infections mimic the symptoms of GAS pharyngitis. Emergency clinicians must
      recognize the symptomatology of GAS pharyngitis and use appropriate means of
      diagnosis and treatment to promote good antibiotic stewardship. This issue
      reviews the signs and symptoms of GAS pharyngitis, as well as associated
      complications, and provides recommendations for appropriate treatment that
      focuses on reducing the severity and duration of symptoms, reducing the incidence
      of nonsuppurative complications, and reducing transmission.

PMID- 29185671
TI  - Managing dislocations of the hip, knee, and ankle in the emergency department
AB  - Dislocation of the major joints of the lower extremities--hip, knee, and ankle-
      can occur due to motor-vehicle crashes, falls, and sports injuries. Hip
      dislocations are the most common, and they require emergent management to prevent
      avascular necrosis of the femoral head. Knee dislocations are uncommon but
      potentially dangerous injuries that can result in amputation due to the potential
      for missed secondary injury, especially if they are reduced spontaneously.
      Isolated ankle dislocations are relatively rare, as most ankle dislocations
      involve an associated fracture. This review presents an algorithmic approach to
      management that ensures that pain relief, imaging, reduction, vascular
      monitoring, and emergent orthopedic consultation are carried out in a timely
      fashion.

PMID- 29185673
TI  - Sentinel lymph node mapping in endometrial cancer: a systematic review and meta
      analysis.
AB  - INTRODUCTION: Appropriate extent of lymphadenectomy in clinically, early stage
      endometrial cancer remains controversial but sentinel lymph node (SLN) mapping
      has emerged as an alternative staging strategy, until the advent of molecular
      prognostic markers. We sought to perform a systematic review of the literature to
      determine pooled estimates for SLN detection rate and diagnostic accuracy, while
      exploring impact of the SLN on adjuvant therapy and oncologic outcomes. EVIDENCE
      ACQUISITION: We performed a systematic search utilizing Medline, EMBASE, and Web
      of Science electronic databases for all studies published in the English language
      until October 31, 2017. Studies were included for review and potential aggregate
      analyses if they contained at least 30 endometrial cancer patients with
      undergoing SLN mapping and reported on detection rates (overall, bilateral or
      para-aortic) or diagnostic accuracy (sensitivity and negative predictive value
      [NPV]). Pooled estimates were calculated via meta-analyses utilizing a random
      effects model. Studies reporting on the impact of SLN on adjuvant therapy, as
      well as studies comparing SLN mapping to completion lymphadenectomy were
      qualitatively reviewed and analyzed as well. EVIDENCE SYNTHESIS: We identified 48
      eligible studies, which included 5348 patients for review and inclusion in the
      meta-analysis for SLN detection or diagnostic accuracy. The pooled SLN detection
      rates were were 87% (95% CI: 84-89%, 44 studies) for overall detection, 61% (95%
      CI: 56-66%, 36 studies) for bilateral detection, and 6% (95% CI: 3-9%, 31
      studies) for para-aortic detection. Indocyanine green use improved overall (94%,
      95% CI: 92-96%, 19 studies) SLN detection rates compared to blue tracer (86%, 95%
      CI: 83-89%, 31 studies) or technetium-99 (86%, 95% CI: 83-89%, 25 studies). This
      trend was similarly seen in terms of bilateral detection rates (74% vs. 59% vs.
      57%, respectively). There was no difference in para-aortic SLN detection rate
      between each tracer. The pooled estimates for diagnostic accuracy for 34 studies
      were 94% (95% CI: 91-96%) for sensitivity and 100% (95% CI: 99 - 100%) for NPV.
      Diagnostic accuracy of SLN mapping was not negatively affected in patients with
      high-grade endometrial histology. Patients with SLN mapping are more likely to
      receive adjuvant therapy and do not have inferior survival or recurrence outcomes
      compared to those undergoing completion lymphadenectomy. CONCLUSIONS: SLN mapping
      is a feasible and accurate alternative to stage patients with endometrial cancer.
      Utilizing indocyanine green results in the highest SLN detection rates. Future
      studies should prospectively examine the impact of SLN mapping on progression
      free and overall survival.

PMID- 29185674
TI  - Effectiveness of Extracorporeal Shock Wave Therapy and kinesio taping in calcific
      tendinopathy of the shoulder: a randomized controlled trial.
AB  - BACKGROUND: Extracorporeal Shock Wave Therapy (ESWT) is effective in the
      treatment of calcific tendinopathy of the rotator cuff, eliciting an
      analgesic/anti-inflammatory action and promoting tissue regeneration. Kinesio
      taping (KT), another recently-introduced rehabilitative tool, exerts an analgesic
      and biomechanical action on joints and muscles. ESWT and KT may have a synergic
      effect when used in combination, but the effectiveness of the association has not
      been established. AIM: The aim of this study was to test if the association of KT
      with ESWT is superior to ESWT alone in the treatment of rotator cuff calcific
      tendinopathy. DESIGN: Randomized controlled trial. SETTING: Rehabilitation
      Institute outpatients. POPULATION: Forty-two patients with rotator cuff calcific
      tendinopathy were randomly assigned to the experimental group (ESWT+KT, N.=21) or
      control (ESWT, N.=21). METHODS: In the experimental group, patients underwent
      three sessions (once a week for 3 weeks) of ESWT with KT applied at the end of
      each session. Controls underwent three sessions of ESWT only. All patients were
      assessed before treatment (T0) and at 1 (T1), 4 (T2) and 12 weeks (T3) after the
      end of treatment with the following outcome measures: a visual analogue scale
      (VAS), the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire,
      Subjective Shoulder Rating Questionnaire (SSRQ), and Oxford Shoulder Score (OSS).
      RESULTS: Both groups showed significant improvement in all outcome measures, but
      the time course differed between the two groups. At T1 vs. T0, the improvement
      was significantly better in ESWT+KT than ESWT on VAS (P=0.007), DASH (P<0.0001)
      and SSRQ (P=0.0001). Successive improvements at T2 vs. T1 and T3 vs. T2 did not
      differ significantly between the groups. At the end of follow-up, ESWT+KT still
      showed significantly greater improvement than ESWT on VAS (P=0.02) and SSRQ
      (P=0.038). CONCLUSIONS: KT associated with ESWT seems to improve the recovery in
      rotator cuff calcific tendinopathy with a faster therapeutic response compared to
      ESWT only. CLINICAL REHABILITATION IMPACT: Our results suggest the effectiveness
      of using KT as adjuvant therapy to ESWT in rotator cuff calcific tendinopathy,
      through enhancing the short-term analgesic action and the medium- to long-term
      biological-regenerative effects.

PMID- 29185675
TI  - Muscle stretching exercises and resistance training in fibromyalgia: which is
      better? A three-arm randomized controlled trial.
AB  - BACKGROUND: Exercise therapy is an effective component of fibromyalgia (FM)
      treatment. However, it is important to know the effects and specificities of the
      different types of exercise: muscle stretching and resistance training. AIM: To
      verify and compare the effectiveness of muscle stretching exercise and resistance
      training for symptoms and quality of life in FM patients. DESIGN: Randomized
      controlled trial. SETTING: Physical therapy service, FM outpatient clinic.
      POPULATION: Forty-four women with FM (79 screened). METHODS: Patients were
      randomly allocated into a stretching group (N.=14), resistance group (N.=16), and
      control group (N.=14). Pain was assessed using the visual analog scale, pain
      threshold using a Fischer dolorimeter, FM symptoms using the Fibromyalgia Impact
      Questionnaire (FIQ), and quality of life using the Medical Outcomes Study 36-item
      Short-Form Health Survey (SF-36). The three intervention groups continued with
      usual medical treatment. In addition, the stretching and resistance groups
      performed two different exercise programs twice a week for 12 weeks. RESULTS:
      After treatment, the stretching group showed the highest SF-36 physical
      functioning score (P=0.01) and the lowest bodily pain score (P=0.01). The
      resistance group had the lowest FIQ depression score (P=0.02). The control group
      had the highest score for FIQ morning tiredness and stiffness, and the lowest
      score for SF-36 vitality. In clinical analyses, the stretching group had
      significant improvement in quality of life for all SF-36 domains, and the
      resistance group had significant improvement in FM symptoms and in quality of
      life for SF-36 domains of physical functioning, vitality, social function,
      emotional role, and mental health. CONCLUSIONS: Muscle stretching exercise was
      the most effective modality in improving quality of life, especially with regard
      to physical functioning and pain, and resistance training was the most effective
      modality in reducing depression. CLINICAL REHABILITATION IMPACT: The trial
      included a control group and two intervention groups, both of which received
      exercise programs created specifically for patients with FM. In clinical
      practice, we suggest including both modalities in an exercise therapy program for
      FM.

PMID- 29185677
TI  - Calculated decisions: Centor Score (Modified/McIsaac) for strep pharyngitis

PMID- 29185676
TI  - Effect of physiotherapeutic intervention on the gait after the application of
      botulinum toxin in children with cerebral palsy: systematic review.
AB  - INTRODUCTION: Cerebral palsy is a group of movement and posture development
      disorders. 90% of this population has gait impairment, often due to the presence
      of spasticity. A number of studies emphasize the importance of combined physical
      therapy with botulinum toxin A treatment. However, no consensus can be reached
      concerning the content of the physiotherapy program after treatment with
      botulinum toxin A. The purpose of the present study was to investigate, through a
      systematic review of the literature, the effects of physiotherapeutic
      intervention on gait after botulinum toxin application in children with cerebral
      palsy. EVIDENCE ACQUISITION: PubMed, Scielo, Cochrane Library, OTseeker, and
      PEDro databases were searched for randomized trial published between January 2000
      and January 2017. EVIDENCE SYNTHESIS: Sixty-eight articles were identified, four
      of which met the eligibility criteria and were selected for the present
      systematic review. A table was created showing the main characteristics of the
      studies (groups, inclusion criteria, dosage, injection site, physiotherapeutic
      intervention, evaluation and outcomes). CONCLUSIONS: This study offers a view on
      the increase in the therapeutic effectiveness of botulinum toxin A on the lower
      limbs when used in conjunction with a physiotherapeutic intervention, with
      improvements in mobility, gait pattern, range of motion and spasticity, which are
      maintained after the end of the physical therapy protocol. The use of botulinum
      toxin A on the lower limbs when used in conjunction with a physiotherapeutic
      intervention, can improve muscle tone, allowing a combined treatment and intended
      to provide improvement of motor ability and functional skills, and potentially,
      delay the need for surgery.

PMID- 29185678
TI  - Loose Marbles: Focusing on safety of crews and patients during transport.

PMID- 29185679
TI  - Distracted Driving: Liability time bombs from smartphones to lights and siren.

PMID- 29185680
TI  - Social Responsibility: Supervising EMS officer competencies.

PMID- 29185681
TI  - Heady Mystery: Intoxicated patient's misplaced memory hides undiscovered trauma.

PMID- 29185682
TI  - Indistinct Anaphylaxis. Study lacks pieces to paint a clear picture.

PMID- 29185683
TI  - Thinking Outside (and Inside) the Box. How Cranberry Township, Pa., designed a
      safer ambulance.

PMID- 29185684
TI  - Lights and Sirens: Improving the safety of the sights and sounds of EMS.

PMID- 29185685
TI  - Take A Seat:  New ambulance seating improves safety, size and functionality.

PMID- 29185686
TI  - The Price of Safety: Comparing the return on investment in safe driving systems.

PMID- 29185687
TI  - Establishing Identity: A New Zealand perspective on organizational culture in
      EMS.

PMID- 29185688
TI  - Streamlining Mental Health Response. Colorado Springs program is changing how EMS
      responds to behavioral health crises.

PMID- 29185689
TI  - From  Beginning to Endotracheal: How to anticipate and treat the most common
      complications of prehospital intubation.

PMID- 29185690
TI  - Mountain Climbing: Finding a path for EMS.

PMID- 29185691
TI  - Hands On: Product Reviews from Street Crews.

PMID- 29185692
TI  - Berry Musing: Preconceived Care. Labeling patients can negate their care.

PMID- 29185693
TI  - Last Word: The Ups and Downs of EMS.

PMID- 29185694
TI  - The Molecular Mechanism of Substrate Recognition and Catalysis of the Membrane
      Acyltransferase PatA from Mycobacteria.
AB  - Glycolipids play a central role in a variety of important biological processes in
      all living organisms. PatA is a membrane acyltransferase involved in the
      biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), key structural
      elements, and virulence factors of Mycobacterium tuberculosis. PatA catalyzes the
      transfer of a palmitoyl moiety from palmitoyl-CoA to the 6-position of the
      mannose ring linked to the 2-position of inositol in PIM1/PIM2. We report here
      the crystal structure of PatA in the presence of 6-O-palmitoyl-alpha-d
      mannopyranoside, unraveling the acceptor binding mechanism. The acceptor mannose
      ring localizes in a cavity at the end of a surface-exposed long groove where the
      active site is located, whereas the palmitate moiety accommodates into a
      hydrophobic pocket deeply buried in the alpha/beta core of the protein. Both
      fatty acyl chains of the PIM2 acceptor are essential for the reaction to take
      place, highlighting their critical role in the generation of a competent active
      site. By the use of combined structural and quantum-mechanics/molecular-mechanics
      (QM/MM) metadynamics, we unravel the catalytic mechanism of PatA at the atomic
      electronic level. Our study provides a detailed structural rationale for a
      stepwise reaction, with the generation of a tetrahedral transition state for the
      rate-determining step. Finally, the crystal structure of PatA in the presence of
      beta-d-mannopyranose and palmitate suggests an inhibitory mechanism for the
      enzyme, providing exciting possibilities for inhibitor design and the discovery
      of chemotherapeutic agents against this major human pathogen.

PMID- 29185695
TI  - Nanosized Difunctional Photo Responsive Magnetic Imprinting Polymer for
      Electrochemically Monitored Light-Driven Paracetamol Extraction.
AB  - Herein, a novel photoresponsive magnetic electrochemical imprinting sensor for
      the selective extraction of paracetamol from biological samples was designed. In
      particular, nanosized photoresponsive molecular imprinted polymers were prepared
      on the surface of magnetic Fe3O4 nanoparticles through living radical
      polymerization of azobenzene. The introduction of a magnetic-controlled glassy
      carbon electrode makes the immobilization and removal of nanosized
      photoresponsive molecular imprinted polymers on the magnetic-controlled glassy
      carbon electrode surface facilely operational. With the photoresponsive property,
      the sensor undergoes reversible release and uptake of paracetamol upon
      alternative irradiation at 365 and 440 nm basing on a configurational change of
      azobenzene monomer in the photoresponsive molecular imprinted polymers receptor
      sites. Simultaneously, these processes are monitored by the photoresponsive
      changes of electrochemical signal from paracetamol. Two linear ranges from 0.001
      to 0.7 mmol L-1 (R2 = 0.96) and 0.7 to 7 mmol L-1 (R2 = 0.95) for paracetamol
      determination were obtained with a quantification limit of 0.000 86 mmol L-1 and
      a detection limit of 0.000 43 mmol L-1. The recoveries of paracetamol in the
      urine as determined by photoresponsive molecular imprinted polymers extraction
      were varied between 87.5% and 93.3%. As a consequence, combining photocontrolled
      selective extraction, interfacial stability from magnetic adsorption, and
      specifically electrochemical response, the photoresponsive molecular imprinted
      polymers sensor shows significant advantages for simultaneous separation,
      enrichment, and detection of trace paracetamol in biological samples.

PMID- 29185696
TI  - Mode of Action and Heterologous Expression of the Natural Product Antibiotic
      Vancoresmycin.
AB  - Antibiotics that interfere with the bacterial cytoplasmic membrane have long-term
      potential for the treatment of infectious diseases as this mode of action is
      anticipated to result in low resistance frequency. Vancoresmycin is an
      understudied natural product antibiotic consisting of a terminal tetramic acid
      moiety fused to a linear, highly oxygenated, stereochemically complex polyketide
      chain. Vancoresmycin shows minimum inhibitory concentrations (MICs) from 0.125 to
      2 MUg/mL against a range of clinically relevant, antibiotic-resistant Gram
      positive bacteria. Through a comprehensive mode-of-action study, utilizing
      Bacillus subtilis reporter strains, DiSC3(5) depolarization assays, and
      fluorescence microscopy, we have shown that vancoresmycin selectively targets the
      cytoplasmic membrane of Gram-positive bacteria via a non-pore-forming,
      concentration-dependent depolarization mechanism. Whole genome sequencing of the
      producing strain allowed identification of the 141 kbp gene cluster encoding for
      vancoresmycin biosynthesis and a preliminary model for its biosynthesis. The size
      and complex structure of vancoresmycin could confound attempts to generate
      synthetic analogues. To overcome this problem and facilitate future studies, we
      identified, cloned, and expressed the 141 kbp biosynthetic gene cluster in
      Streptomyces coelicolor M1152. Elucidation of the mode-of-action of
      vancoresmycin, together with the heterologous expression system, will greatly
      facilitate further studies of this and related molecules.

PMID- 29185697
TI  - Donor-Acceptor-Type S,N-Heteroacene-Based Hole-Transporting Materials for
      Efficient Perovskite Solar Cells.
AB  - Two new donor-acceptor (D-A)-substituted S,N-heteroacene-based molecules were
      developed and investigated as hole-transporting material (HTM) for perovskite
      solar cells (PSCs). Optical and electrochemical characterization brought out that
      the energy levels of both HTMs are suitable for their use in PSCs. Consequently,
      a power-conversion efficiency of 17.7% and 16.1% was achieved from PSCs involving
      the HTM-1 and HTM-2, respectively. The optoelectronic properties in terms of
      series resistance, conductivity, and charge carrier recombination were further
      examined to unfold the potential of these new HTMs. Time-resolved
      photoluminescence spectroscopy brought out that the hole injection from the
      valence band of perovskite into HTMs follows the trend, which is in accordance
      with the position of the highest occupied molecular orbital. Overall, our
      findings underline the potential of S,N-heteroacene co-oligomers as promising HTM
      candidates for PSCs.

PMID- 29185698
TI  - Suppressing Shuttle Effect Using Janus Cation Exchange Membrane for High
      Performance Lithium-Sulfur Battery Separator.
AB  - Suppressing the shuttle effect of polysulfide ions to obtain high durability and
      good electrochemical performance is of great concern in the field of lithium
      sulfur batteries. To address this issue, a Janus membrane consisting of an
      ultrathin dense layer and a robust microporous layer is fabricated using cation
      exchange resin. Different from the composite membranes made from polyolefin
      membranes, the multiple layers of the Janus membrane in this study are
      synchronously generated by one step, getting rid of the additional complex
      coating processes. Excellent overall performance is obtained by the cooperation
      of multiple factors. The excellent ionic selectivity of cation exchange resin
      renders a great suppression of the shuttle effect, endowing the lithium-sulfur
      battery with high Coulombic efficiency of 92.0-99.0% (LiNO3-free electrolyte).
      The ultrathin property of a dense layer renders a low ionic resistance, resulting
      in 60% higher discharge capacity over the entire C-rates (versus the control
      sample with Celgard 2400 membrane). The robust macroporous layer supports the
      ultrathin layer to achieve a free-standing property, ensuring the usability of
      the Janus membrane.

PMID- 29185699
TI  - Mesoporous Iron Oxide Synthesized Using Poly(styrene-b-acrylic acid-b-ethylene
      glycol) Block Copolymer Micelles as Templates for Colorimetric and
      Electrochemical Detection of Glucose.
AB  - Herein, we report the soft-templated preparation of mesoporous iron oxide using
      an asymmetric poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG)
      triblock copolymer. This polymer forms a micelle consisting of a PS core, a PAA
      shell, and a PEG corona in aqueous solutions, which can serve as a soft template.
      The mesoporous iron oxide obtained at an optimized calcination temperature of 400
      degrees C exhibited an average pore diameter of 39 nm, with large specific
      surface area and pore volume of 86.9 m2 g-1 and 0.218 cm3 g-1, respectively. The
      as-prepared mesoporous iron oxide materials showed intrinsic peroxidase-like
      activities toward the catalytic oxidation of 3,3',5,5'-tertamethylbenzidine (TMB)
      in the presence of hydrogen peroxide (H2O2). This mimetic feature was further
      exploited to develop a simple colorimetric (naked-eye) and electrochemical assay
      for the detection of glucose. Both our colorimetric (naked-eye and UV-vis) and
      electrochemical assays estimated the glucose concentration to be in the linear
      range from 1.0 MUM to 100 MUM with a detection limit of 1.0 MUM. We envisage that
      our integrated detection platform for H2O2 and glucose will find a wide range of
      applications in developing various biosensors in the field of personalized
      medicine, food-safety detection, environmental-pollution control, and agro
      biotechnology.

PMID- 29185700
TI  - Design and Application of a DNA-Encoded Macrocyclic Peptide Library.
AB  - A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 *
      1012 members composed of 4-20 natural and non-natural amino acids. Affinity-based
      selection was performed against two therapeutic targets, VHL and RSV N protein.
      On the basis of selection data, some peptides were selected for resynthesis
      without a DNA tag, and their activity was confirmed.

PMID- 29185701
TI  - Strategy for the Improvement of the Mechanical Properties of Cellulose Nanofiber
      Reinforced High-Density Polyethylene Nanocomposites Using Diblock Copolymer
      Dispersants.
AB  - Cellulose nanofibers (CNFs) hold great potential as sustainable reinforcement
      fillers with excellent mechanical, thermal, and chemical properties. However, in
      polyolefin nanocomposite materials, the rational control of dispersion and the
      improvement of interfacial strength remain challenging. Herein we propose the
      tuning of the interface between CNF and high-density polyethylene by the design
      of polymer dispersants on the basis of surface free energy and the glass
      transition temperature. The former is related to the wettability against the
      polymer matrix and is therefore critical to the dispersion of CNF whereas the
      latter is related to the interfacial strength between CNF and HDPE. As a result
      of this investigation, we discovered a suitable dispersant for CNFs,
      poly(dicyclopentenyloxyethyl methacrylate)-block-poly(2-hydroxyethyl
      methacrylate), which played a pivotal role in achieving both a uniform dispersion
      of CNF and greatly improved mechanical properties, including a 4-fold increase of
      the Young's modulus over that of neat HDPE with 10 wt % CNF loading.

PMID- 29185702
TI  - Tailoring Fluorescence Brightness and Switching of Nanoparticles through Dye
      Organization in the Polymer Matrix.
AB  - Fluorescent nanoparticles (NPs) help to increase spatial and temporal resolution
      in bioimaging. Advanced microscopy techniques require very bright NPs that
      exhibit either stable emission for single-particle tracking or complete on/off
      switching (blinking) for super-resolution imaging. Here, ultrabright dye-loaded
      polymer NPs with controlled switching properties are developed. To this aim, the
      salt of a dye (rhodamine B octadecyl ester) with a hydrophobic counterion
      (fluorinated tetraphenylborate) is encapsulated at very high concentrations up to
      30 wt % in NPs made of poly(lactic-co-glycolic acid) (PLGA), poly(methyl
      methacrylate) (PMMA), and polycaprolactone (PCL) through nanoprecipitation. The
      obtained 35 nm NPs are nearly 100 times brighter than quantum dots. The nature of
      the polymer is found to define the collective behavior of the encapsulated dyes
      so that NPs containing thousands of dyes exhibit either whole particle blinking,
      for PLGA, or stable emission, for PMMA and PCL. Fluorescence anisotropy
      measurements together with small-angle X-ray scattering experiments suggest that
      in less hydrophobic PLGA, dyes tend to cluster, whereas in more hydrophobic PMMA
      and PCL, dyes are dispersed within the matrix, thus altering the switching
      behavior of NPs. Experiments using a perylene diimide derivative show a similar
      effect of the polymer nature. The resulting fluorescent NPs are suitable for a
      wide range of imaging applications from tracking to super-resolution imaging. The
      findings on the organization of the load innside NPs will have impact on the
      development of materials for applications ranging from photovoltaics to drug
      delivery.

PMID- 29185703
TI  - Homospermidine Lipids: A Compound Class Specifically Formed during Fruiting Body
      Formation of Myxococcus xanthus DK1622.
AB  - The fascinating ability of myxobacteria to form multicellular spore filled
      fruiting bodies under starvation conditions was widely studied as a model for
      cooperative microbial behavior. The potential of a life cycle induced change of
      secondary metabolism, as a means to discover novel natural products, remains
      largely underexplored. We therefore studied the model organism Myxococcus xanthus
      DK1622 under submersed and solid cultivation conditions to find putatively life
      cycle related compounds by applying statistical analysis on analytical data.
      Utilizing the advantageous characteristics of LC-MS, LC-MS/MS, and MALDI-MSI
      allowed the identification of compounds unambiguously associated with
      myxobacterial fruiting bodies. Our screening effort resulted in the purification
      and structure elucidation of a novel compound, the homospermidine lipid, from
      cultures that had undergone the fruiting process. A combination of molecular
      networking and targeted LC-MS/MS in conjunction with our in-house metabolomics
      database subsequently revealed alternative producers of the respective compound
      as well as a number of compounds belonging to the same structural class. Three
      further members of this compound class were isolated from an alternative producer
      and structurally elucidated by NMR. Insights into the biosynthesis of this novel
      compound class was gained by feeding of isotopically labeled substrates and in
      silico analysis.

PMID- 29185704
TI  - Functional Design of Highly Robust and Flexible Thin-Film Encapsulation Composed
      of Quasi-Perfect Sublayers for Transparent, Flexible Displays.
AB  - In this study, a structurally and materially designed thin-film encapsulation is
      proposed to guarantee the reliability of transparent, flexible displays by
      significantly improving their barrier properties, mechanical stability, and
      environmental reliability, all of which are essential for organic light-emitting
      diode (OLED) encapsulation. We fabricated a bioinspired, nacre-like ZnO/Al2O3/MgO
      laminate structure (ZAM) using atomic layer deposition for the microcrack
      toughening effect. The ZAM film was formed with intentional voids and defects
      through the formation of a quasi-perfect sublayer, rather than the simple
      fabrication of nanolaminate structures. The 240 nm thick ZAM-based multibarrier
      (ZAM-TFE) with a compressively strained organic layer demonstrated an optical
      transmittance of 91.35% in the visible range, an extremely low water vapor
      transmission rate of 2.06 * 10-6 g/m2/day, a mechanical stability enduring a
      strain close to 1%, and a residual stress close to 0, showing significant
      improvement of key TFE properties in comparison to an Al2O3-based multibarrier.
      In addition, ZAM-TFE demonstrated superior environmental resistance without
      degradation of barrier properties in a severe environment of 85  degrees C and
      90% relative humidity (RH). Thus, our structurally and materially designed ZAM
      film has been well optimized in terms of its applicability as a gas diffusion
      barrier as well as in terms of its mechanical and environmental reliability.
      Finally, we confirmed the feasibility of the ZAM-TFE through application in
      OLEDs. The low-temperature ZAM-TFE technology showed great potential to provide a
      highly robust and flexible TFE of TFOLEDs.

PMID- 29185705
TI  - Ultrathin Polydiacetylene-Based Synergetic Composites with Plasmon-Enhanced
      Photoelectric Properties.
AB  - Fabricating plasmon-enhanced organic nanomaterials with technologically relevant
      supporting architectures on planar solids remains a challenging task in the
      chemistry of thin films and interfaces. In this work, we report a bottom-up
      assembly of ultrathin layered composites of conductive polymers with
      photophysical properties enhanced by gold nanoparticles. The polydiacetylene
      component was formed by photopolymerization of a catanionic mixture of
      pentacosadiynoic surfactants on a surface of citrate-stabilized gold hydrosol
      monitored by a fiber optic spectrometer. Microscopic examination of the 3 nm
      thick solid-immobilized film showed that gold nanoparticles (AuNPs) do not
      aggregate within the monolayer upon polymerization. This polydiacetylene/AuNPs
      monolayer was coupled with 60 nm thick polyaniline-based layer deposited atop.
      The resulting polymer composite with an integrated 4-stripe electric cell showed
      nonadditive electric behavior due to the formation of electron-hole pairs with
      increased charge carrier mobility at the interface between the polymer layers.
      Under visible light irradiation of the composite film, a plasmonic effect of the
      gold nanoparticles was observed at the onset of photoconductivity, although
      neither polydiacetylene nor the polyaniline component alone are photoconductive
      polymers. The results indicate that our bottom-up strategy can be expanded to
      design other plasmon-enhanced ultrathin polymer composites with potential
      applications in optoelectronics and photovoltaics.

PMID- 29185706
TI  - Scalable Production of Graphene-Based Wearable E-Textiles.
AB  - Graphene-based wearable e-textiles are considered to be promising due to their
      advantages over traditional metal-based technology. However, the manufacturing
      process is complex and currently not suitable for industrial scale application.
      Here we report a simple, scalable, and cost-effective method of producing
      graphene-based wearable e-textiles through the chemical reduction of graphene
      oxide (GO) to make stable reduced graphene oxide (rGO) dispersion which can then
      be applied to the textile fabric using a simple pad-dry technique. This
      application method allows the potential manufacture of conductive graphene e
      textiles at commercial production rates of ~150 m/min. The graphene e-textile
      materials produced are durable and washable with acceptable softness/hand feel.
      The rGO coating enhanced the tensile strength of cotton fabric and also the
      flexibility due to the increase in strain% at maximum load. We demonstrate the
      potential application of these graphene e-textiles for wearable electronics with
      activity monitoring sensor. This could potentially lead to a multifunctional
      single graphene e-textile garment that can act both as sensors and flexible
      heating elements powered by the energy stored in graphene textile
      supercapacitors.

PMID- 29185707
TI  - Atomic-Scale Choreography of Vapor-Liquid-Solid Nanowire Growth.
AB  - Functional materials and devices require nanoscale control of morphology, crystal
      structure, and composition. Vapor-liquid-solid (VLS) crystal growth and its
      related growth modes enable the synthesis of 1D nanostructures, commonly called
      "nanowires", where the necessary nanoscale heterogeneity can be encoded axially.
      During the VLS process, a seed particle collects atoms and directs the nucleation
      of crystalline material. Modulating the delivery of growth species or conditions
      permits compositional and/or structural encoding. A range of materials and
      devices (e.g., for electronics, photonics, thermal transport, and bioprobes) have
      been produced by VLS growth, but plenty of challenges remain: many desirable
      structures cannot currently be made, and even for those structures that can be
      made, the parameter window-in terms of, e.g., temperatures and pressures-is often
      narrow. Moreover, we are quite far from ab initio determination of which growth
      conditions should be used or even if a desired structure is fundamentally
      achievable within the VLS framework. To fully understand the challenges and
      promises of VLS growth, the governing physicochemical processes must be explored
      and understood at the atomic scale. This final level of detail is being unraveled
      with the help of in situ characterization techniques. The picture that is
      emerging is of a highly dynamical process with several deeply interconnected and
      highly fundamental components that are difficult to detect with postgrowth ex
      situ interrogation. For example, recent in situ microscopy and spectroscopy
      studies have shown that the growth front can undergo cyclical reshaping involving
      dissolution as well as crystallization and that the state of the nanowire
      surface, which changes with growth conditions as a result of a competition
      between adsorption and desorption of passivating species, plays a crucial role in
      determining the transport to/from and the stability of the seed particle. The
      available in situ observations currently constitute a somewhat disparate list,
      but if they can be connected to each other and to the outstanding challenges,
      they promise meaningful advances in our understanding of VLS growth. In this
      Account, we review the state of the art regarding the atomic-scale thermodynamic
      and kinetic phenomena that control VLS growth. Rather than cataloging all of the
      outstanding contributions to the field, we give priority to in situ observations
      that have revealed unexpected effects as well as those that hint at incongruities
      in our current knowledge. As such, our discussion should be viewed as an
      opportunity to gain deeper understanding and control of the fundamental processes
      at play, which will be crucial in future scale-up efforts and expansion to
      completely new materials systems and application areas.

PMID- 29185709
TI  - Rett Syndrome: A Genetic Update and Clinical Review Focusing on Comorbidities.
AB  - Rett syndrome (RTT) is a unique neurodevelopmental disorder that primarily
      affects females resulting in severe cognitive and physical disabilities. Despite
      the commendable collective efforts of the research community to better understand
      the genetics and underlying biology of RTT, there is still no cure. However, in
      the past 50 years, since the first report of RTT, steady progress has been made
      in the accumulation of clinical and molecular information resulting in the
      identification of a number of genes associated with RTT and associated
      phenotypes, improved diagnostic criteria, natural history studies, curation of a
      number of databases capturing genotypic and phenotypic data, a number of
      promising clinical trials and exciting novel therapeutic options which are
      currently being tested in laboratory and clinical settings. This Review focuses
      on the current knowledge of the clinical aspects of RTT, with particular
      attention being paid to clinical trials and the comorbidities of the disorder as
      well as the genetic etiology and the recognition of new diseases genes.

PMID- 29185708
TI  - The Autophagy-Related Beclin-1 Protein Requires the Coiled-Coil and BARA Domains
      To Form a Homodimer with Submicromolar Affinity.
AB  - Beclin-1 (BECN1) is an essential component of macroautophagy. This process is a
      highly conserved survival mechanism that recycles damaged cellular components or
      pathogens by encasing them in a bilayer vesicle that fuses with a lysosome to
      allow degradation of the vesicular contents. Mutations or altered expression
      profiles of BECN1 have been linked to various cancers and neurodegenerative
      diseases. Viruses, including HIV and herpes simplex virus 1 (HSV-1), are also
      known to specifically target BECN1 as a means of evading host defense mechanisms.
      Autophagy is regulated by the interaction between BECN1 and Bcl-2, a pro-survival
      protein in the apoptotic pathway that stabilizes the BECN1 homodimer. Disruption
      of the homodimer by phosphorylation or competitive binding promotes autophagy
      through an unknown mechanism. We report here the first recombinant synthesis (3-5
      mg/L in an Escherichia coli culture) and characterization of full-length, human
      BECN1. Our analysis reveals that full-length BECN1 exists as a soluble homodimer
      (KD ~ 0.45 MUM) that interacts with Bcl-2 (KD = 4.3 +/- 1.2 MUM) and binds to
      lipid membranes. Dimerization is proposed to be mediated by a coiled-coil region
      of BECN1. A construct lacking the C-terminal BARA domain but including the coiled
      coil region exhibits a homodimer KD 3.5-fold weaker than that of full-length
      BECN1, indicating that both the BARA domain and the coiled-coil region of BECN1
      contribute to dimer formation. Using site-directed mutagenesis, we show that
      residues at the C-terminus of the coiled-coil region previously shown to interact
      with the BARA domain play a key role in dimerization and mutations weaken the
      interface by ~5-fold.

PMID- 29185710
TI  - Quantum Dots of 1T Phase Transitional Metal Dichalcogenides Generated via
      Electrochemical Li Intercalation.
AB  - We prepare group VI transitional metal dichalcogenides (TMDs, or MX2) from the 1T
      phase with quantum-sized and monolayer features via a quasi-full electrochemical
      process. The resulting two-dimensional (2D) MX2 (M = W, Mo; X = S, Se) quantum
      dots (QDs) are ca. 3.0-5.4 nm in size with a high 1T phase fraction of ca. 92%
      97%. We attribute this to the high Li content intercalated in the 1T-MX2 lattice
      (mole ratio of Li:M is over 2:1), which is achieved by an increased lithiation
      driving force and a reduced electrochemical lithiation rate (0.001 A/g). The high
      Li content not only promotes the 2H -> 1T phase transition but also generates
      significant inner stress that facilitates lattice breaking for MX2 crystals.
      Because of their high proportion of metallic 1T phase and sufficient active sites
      induced by the small lateral size, the 2D 1T-MoS2 QDs show excellent hydrogen
      evolution reactivity (with a typical eta10 of 92 mV, Tafel slope of 44 mV/dec,
      and J0 of 4.16 * 10-4 A/cm2). This electrochemical route toward 2D QDs might help
      boost the development of 2D materials in energy-related areas.

PMID- 29185713
TI  - Correction to Ion-Selective Nanosensor for Photoacoustic and Fluorescence Imaging
      of Potassium.

PMID- 29185712
TI  - Ragtime Regulation: Mechanism of TORC1 Activation in Nutrient Sensing.

PMID- 29185711
TI  - Discovery and Biological Evaluation of Potent and Selective N-Methylene Saccharin
      Derived Inhibitors for Rhomboid Intramembrane Proteases.
AB  - Rhomboids are intramembrane serine proteases and belong to the group of
      structurally and biochemically most comprehensively characterized membrane
      proteins. They are highly conserved and ubiquitously distributed in all kingdoms
      of life and function in a wide range of biological processes, including epidermal
      growth factor signaling, mitochondrial dynamics, and apoptosis. Importantly,
      rhomboids have been associated with multiple diseases, including Parkinson's
      disease, type 2 diabetes, and malaria. However, despite a thorough understanding
      of many structural and functional aspects of rhomboids, potent and selective
      inhibitors of these intramembrane proteases are still not available. In this
      study, we describe the computer-based rational design, chemical synthesis, and
      biological evaluation of novel N-methylene saccharin-based rhomboid protease
      inhibitors. Saccharin inhibitors displayed inhibitory potency in the
      submicromolar range, effectiveness against rhomboids both in vitro and in live
      Escherichia coli cells, and substantially improved selectivity against human
      serine hydrolases compared to those of previously known rhomboid inhibitors.
      Consequently, N-methylene saccharins are promising new templates for the
      development of rhomboid inhibitors, providing novel tools for probing rhomboid
      functions in physiology and disease.

PMID- 29185714
TI  - Biochemical Basis of Vosevi, a New Treatment for Hepatitis CPublished as part of
      the Biochemistry series "Biochemistry to Bedside".

PMID- 29185715
TI  - Quantitative Framework for Stochastic Nanopore Sensors Using Multiple Channels.
AB  - Membrane protein channels employed as stochastic sensors offer large signal-to
      noise ratios and high specificity in single molecule binding measurements.
      Stochastic events in a single ion channel system can be measured using current
      time traces, which are straightforward to analyze. Signals arising from
      measurement using multiple ion channels are more complicated to interpret. We
      show that multiple independent ion channels offer improved detection sensitivity
      compared to single channel measurements and that increased signal complexity can
      be accounted for using binding event frequency. More specifically, the leading
      edge of binding events follows a Poisson point process, which means signals from
      multiple channels can be superimposed and the association times (between each
      binding event leading edge), allow for sensitive and quantitative measurements.
      We expand our calibration to high ligand concentrations and high numbers of ion
      channels to demonstrate that there is an upper limit of quantification, defined
      by the time resolution of the measurement. The upper limit is a combination of
      the instrumental time resolution and the dissociation time of a ligand and
      protein which limits the number of detectable events. This upper limit also
      allows us to predict, in general, the measurement requirements needed to observe
      any process as a Poisson point process. The nanopore-based sensing analysis has
      wide implications for stochastic sensing platforms that operate using multiple
      simultaneous superimposable signals.

PMID- 29185716
TI  - Pollutants in Plastics within the North Pacific Subtropical Gyre.
AB  - Here we report concentrations of pollutants in floating plastics from the North
      Pacific accumulation zone (NPAC). We compared chemical concentrations in plastics
      of different types and sizes, assessed ocean plastic potential risks using
      sediment quality criteria, and discussed the implications of our findings for
      bioaccumulation. Our results suggest that at least a fraction of the NPAC
      plastics is not in equilibrium with the surrounding seawater. For instance, "hard
      plastic" samples had significantly higher PBDE concentrations than "nets and
      ropes" samples, and 29% of them had PBDE composition similar to a widely used
      flame-retardant mixture. Our findings indicate that NPAC plastics may pose a
      chemical risk to organisms as 84% of the samples had at least one chemical
      exceeding sediment threshold effect levels. Furthermore, our surface trawls
      collected more plastic than biomass (180 times on average), indicating that some
      NPAC organisms feeding upon floating particles may have plastic as a major
      component of their diets. If gradients for pollutant transfer from NPAC plastic
      to predators exist (as indicated by our fugacity ratio calculations), plastics
      may play a role in transferring chemicals to certain marine organisms.

PMID- 29185718
TI  - Correction to Modeling and Optimization of Recycled Water Systems to Augment
      Urban Groundwater Recharge through Underutilized Stormwater Spreading Basins.

PMID- 29185717
TI  - High Pressure Size Exclusion Chromatography (HPSEC) Determination of Dissolved
      Organic Matter Molecular Weight Revisited: Accounting for Changes in Stationary
      Phases, Analytical Standards, and Isolation Methods.
AB  - We reassessed the molecular weight of dissolved organic matter (DOM) determined
      by high pressure size exclusion chromatography (HPSEC) using measurements made
      with different columns and various generations of polystyrenesulfonate (PSS)
      molecular weight standards. Molecular weight measurements made with a newer
      generation HPSEC column and PSS standards from more recent lots are roughly 200
      to 400 Da lower than initial measurements made in the early 1990s. These updated
      numbers match DOM molecular weights measured by colligative methods and fall
      within a range of values calculated from hydroxyl radical kinetics. These changes
      suggest improved accuracy of HPSEC molecular weight measurements that we
      attribute to improved accuracy of PSS standards and changes in the column
      packing. We also isolated DOM from wetlands in the Prairie Pothole Region (PPR)
      using XAD-8, a cation exchange resin, and PPL, a styrene-divinylbenzene media,
      and observed little difference in molecular weight and specific UV absorbance at
      280 nm (SUVA280) between the two solid phase extraction resins, suggesting they
      capture similar DOM moieties. PPR DOM also showed lower SUVA280 at similar
      weights compared to DOM isolates from a global range of environments, which we
      attribute to oxidized sulfur in PPR DOM that would increase molecular weight
      without affecting SUVA280.

PMID- 29185719
TI  - A Novel Domain Assembly Routine for Creating Full-Length Models of Membrane
      Proteins from Known Domain Structures.
AB  - Membrane proteins composed of soluble and membrane domains are often studied one
      domain at a time. However, to understand the biological function of entire
      protein systems and their interactions with each other and drugs, knowledge of
      full-length structures or models is required. Although few computational methods
      exist that could potentially be used to model full-length constructs of membrane
      proteins, none of these methods are perfectly suited for the problem at hand.
      Existing methods require an interface or knowledge of the relative orientations
      of the domains or are not designed for domain assembly, and none of them are
      developed for membrane proteins. Here we describe the first domain assembly
      protocol specifically designed for membrane proteins that assembles intra- and
      extracellular soluble domains and the transmembrane domain into models of the
      full-length membrane protein. Our protocol does not require an interface between
      the domains and samples possible domain orientations based on backbone dihedrals
      in the flexible linker regions, created via fragment insertion, while keeping the
      transmembrane domain fixed in the membrane. For five examples tested, our method
      mp_domain_assembly, implemented in RosettaMP, samples domain orientations close
      to the known structure and is best used in conjunction with experimental data to
      reduce the conformational search space.

PMID- 29185720
TI  - Electric-Field-Induced Reorientation of the Magnetic Easy Plane in a Co
      Substituted BiFeO3 Single Crystal.
AB  - Single crystals of BiFe0.9Co0.1O3 and BiFe0.892Mn0.008Co0.1O3, room temperature
      ferroelectric ferromagnets, were successfully grown by a flux method at a high
      pressure of 3 GPa. Remanent magnetization measurements along 18 crystallographic
      directions revealed the existence of a magnetic easy plane perpendicular to the
      electric polarization. Reorientation of the magnetic easy plane occurred in
      connection with 71 degrees  ferroelectric switching by applying an electric
      field. This is the first demonstration of an electric field affecting the local
      magnetic moment of Co-substituted BiFeO3.

PMID- 29185721
TI  - Deviations from the Most Spherical Deltahedra in Rhenatricarbaboranes Having 2n +
      2 Wadean Skeletal Electrons.
AB  - Density functional theory studies on the rhenatricarbaboranes C3Bn-4Hn-1Re(CO)3
      (n = 7-12) show that the lowest energy polyhedra for n-vertex metallaboranes
      having 2n + 2 skeletal electrons and sufficiently dissimilar vertex atoms can
      deviate from the most spherical closo deltahedra predicted by application of the
      Wade-Mingos rules. Furthermore, the lowest energy structures of these
      rhenatricarbaboranes are found to avoid C-C edges and have carbon atoms located
      at degree 4 rather than degree 5 vertices. The lowest energy structures for the 7
      vertex C3B3H6Re(CO)3 system all have a central C3B3Re closo deltahedron, namely
      the pentagonal bipyramid with the rhenium atom at a degree 5 axial vertex and all
      three carbon atoms at degree 4 equatorial vertices. However, the lowest energy
      structure for the 8-vertex C3B4H7Re(CO)3 is not the most spherical closo 8-vertex
      deltahedron, namely the bisdisphenoid, but instead a central C3B4Re hexagonal
      bipyramid with mutually nonadjacent degree 4 vertices for the carbon atoms.
      Similarly, the lowest energy 10-vertex C3B6H9Re(CO)3 structures are derived from
      isocloso deltahedra having three degree 4 vertices for all three carbon atoms
      rather than from the most spherical 10-vertex closo deltahedron, namely the
      bicapped square antiprism with only two degree 4 vertices. However, for the 9
      vertex C3B5H8Re(CO)3 system, the most spherical closo deltahedron, namely the
      tricapped trigonal prism, has three mutually nonadjacent degree 4 vertices, which
      is ideal for the three carbon atoms and thus is the preferred deltahedron. The
      preferred deltahedron for the 11-vertex C3B7H10Re(CO)3 remains the most spherical
      closo deltahedron despite having only two degree 4 vertices for the carbon atoms.
      Furthermore, the six lowest energy 12-vertex C3B8H11Re(CO)3 structures are all
      based on the regular icosahedron generally favored in polyhedral borane chemistry
      despite its complete lack of degree 4 vertices for the carbon atoms.

PMID- 29185722
TI  - Valence-Tautomeric Interconversion in a Bis(dioxolene)cobalt Complex with
      Iminopyridine Functionalized by a TEMPO Moiety. Phase Transition Coupled with
      Monocrystal Destruction.
AB  - Iminopyridine modified by TEMPO nitroxide was utilized for the synthesis of an
      octahedral bis(o-semiquinonato)cobalt complex. Variable-temperature magnetic
      susceptibility measurements detect a valence tautomeric transformation in the
      temperature range 200-300 K. A reproducible hysteresis loop of about 40 K width
      is observed on the magnetic moment temperature dependence in the transition
      region. Differential scanning calorimetry measurements confirm different
      temperatures of phase transitions accompanying a valence-tautomeric
      transformation upon heating and cooling. Attempts to study the structural changes
      associated with the valence-tautomeric transformation by single-crystal X-ray
      diffraction failed because of the crystal destruction taking place upon cooling
      from 220 K. The powder X-ray diffraction pattern indicated an essential change of
      the unit cell upon cooling from 240 K.

PMID- 29185723
TI  - Phase Transitions of Thermoelectric TAGS-85.
AB  - The alloys (GeTe)x(AgSbTe2)100-x, commonly known as TAGS-x, are among the best
      performing p-type thermoelectric materials for the composition range 80 <= x <=
      90 and in the temperature range 200-500  degrees C. They adopt a rhombohedrally
      distorted rocksalt structure at room temperature and are reported to undergo a
      reversible phase transition to a cubic structure at ~250  degrees C. However, we
      show that, for the optimal x = 85 composition (TAGS-85), both the structural and
      thermoelectric properties are highly sensitive to the initial synthesis method
      employed. Single-phase rhombohedral samples exhibit the best thermoelectric
      properties but can only be obtained after an annealing step at 600  degrees C
      during initial cooling from the melt. Under faster cooling conditions, the
      samples obtained are inhomogeneous, containing multiple rhombohedral phases with
      a range of lattice parameters and exhibiting inferior thermoelectric properties.
      We also find that when the room-temperature rhombohedral phase is heated, an
      intermediate trigonal structure containing ordered cation vacancy layers is
      formed at ~200  degrees C, driven by the spontaneous precipitation of argyrodite
      type Ag8GeTe6 which alters the stoichiometry of the TAGS-85 matrix. The
      rhombohedral and trigonal phases of TAGS-85 coexist up to 380  degrees C, above
      which a single cubic phase is obtained and the Ag8GeTe6 precipitates redissolve
      into the matrix. On subsequent cooling a mixture of rhombohedral, trigonal, and
      Ag8GeTe6 phases is again obtained. Initially single-phase samples exhibit
      thermoelectric power factors of up to 0.0035 W m-1 K-2 at 500  degrees C, a value
      that is maintained on subsequent thermal cycling and which represents the highest
      power factor yet reported for undoped TAGS-85. Therefore, control over the
      structural homogeneity of TAGS-85 as demonstrated here is essential in order to
      optimize the thermoelectric performance.

PMID- 29185724
TI  - Bonding of Butylparaben, Bis(2-ethylhexyl)-phthalate, and Perfluorooctanesulfonic
      Acid to DNA: Comparison with Benzo[a]pyrene Shows Low Probability for Strong
      Noncovalent DNA Intercalation.
AB  - Parabens, phthalates, and perfluorinated compounds are pollutant compounds used
      in cosmetics, plastics, and fire-fighting foams. All three compounds have been
      studied over several years for toxicity mechanism; however, a clear view of their
      ability to bind to DNA has not been supplied empirically. In this work, a
      simulation study is done to reveal the interaction of three of these pollutants,
      bis(2-ethylhexyl)-phthalate (DEHP), butylparaben (BPRB), and the protonated form
      of perfluorooctanesulfonic acid (PFOS(H)), with DNA. The results show that the
      DEHP, PFOS(H), and BPRB bind with a probability of 1/5 to DNA, with respective
      bonding energies -23.96 kJ/mol (PFOS(H)), -94.92 kJ/mol (BPRB), and -216.52
      kJ/mol (DEHP). The positive control, benzo[a]pyrene diol epoxide (BAP), which is
      known for its notorious DNA intercalation, binds at a rate of 3/5 simulations,
      with bonding energies of -6544.52, -7034.66, and -7578.67 kJ/mol. The results are
      compared to empirical studies and conclusively show that all these pollutants can
      interfere with transcription and DNA related mechanisms by forming noncovalent
      interactions with DNA. The results show also that these pollutants are unlikely
      to undergo strong noncovalent intercalation to DNA, such as BAP, and do not
      possess the frontier orbital profiles to undergo adduct formation. After many
      years of research and several unanswered questions on the action of these
      pollutants on DNA, a calculation on their properties hence to the DNA confirms
      that there is a low probability for these to undergo a strong intercalation with
      DNA. Literature shows however that the pollutants are strongly interfering with
      the protein machinery and receptors on the cell surface and are therefore still
      priority pollutants for ecotoxicity research.

PMID- 29185725
TI  - Stepwise Construction of Heterobimetallic Cages by an Extended Molecular Library
      Approach.
AB  - Two novel heterobimetallic complexes, a trigonal-bipyramidal and a cubic one,
      have been synthesized and characterized using the same C3-symmetric
      metalloligand, prepared by a simple subcomponent self-assembly strategy. Adopting
      the molecular library approach, we chose a mononuclear, preorganized iron(II)
      complex as the metalloligand capable of self-assembly into a trigonal-bipyramidal
      or a cubic aggregate upon coordination to cis-protected C2-symmetric
      palladium(II) or unprotected tetravalent palladium(II) ions, respectively. The
      trigonal-bipyramidal complex was characterized by NMR and UV-vis spectroscopy,
      electrospray ionization mass spectrometry (ESI-MS), and single-crystal X-ray
      diffraction. The cubic structure was characterized by NMR and UV-vis spectroscopy
      and ESI-MS.

PMID- 29185726
TI  - From Allylic Sulfoxides to Allylic Sulfenates: Fifty Years of a Never-Ending
      [2,3]-Sigmatropic Rearrangement.
AB  - The [2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenates
      is a reversible process, generally shifted toward the sulfoxide. In the presence
      of thiophiles, the sulfenate is trapped, and allylic alcohols are obtained under
      mild conditions. In most cases, a good transfer of stereochemical information
      through an ordered transition state is obtained. Furthermore, the ease of
      coupling this process with other versatile, stereocontrolled reactions has
      enhanced the usefulness of this protocol. This review aims to provide a
      comprehensive survey of this rearrangement and its application in the synthesis
      of natural and bioactive products.

PMID- 29185727
TI  - Hyperfine Effects in Ligand NMR: Paramagnetic Ru(III) Complexes with 3
      Substituted Pyridines.
AB  - NMR spectroscopy is an indispensable tool in characterizing molecular systems,
      including transition-metal complexes. However, paramagnetic transition-metal
      complexes such as those with ruthenium in the +3 oxidation state are
      troublemakers because their unpaired electrons induce a fast nuclear spin
      relaxation that significantly broadens their NMR resonances. We recently
      demonstrated that the electronic and spin structures of paramagnetic Ru(III)
      systems can be characterized in unprecedented details by combining experimental
      NMR results with relativistic density-functional theory ( Novotny et al. J. Am.
      Chem. Soc. 2016 , 138 , 8432 ). In this study we focus on paramagnetic analogs of
      NAMI with the general structure [3-R-pyH]+trans-[RuIIICl4(DMSO)(3-R-py)]-, where
      3-R-py stands for a 3-substituted pyridine. The experimental NMR data are
      interpreted in terms of the contributions of hyperfine (HF) NMR shielding and the
      distribution of spin density calculated using relativistic DFT. The DFT
      computational methodology is evaluated, and the effects of substituents,
      environment, and relativity on the hyperfine shielding are discussed. Particular
      attention is paid to the analysis of the fundamental Fermi-contact (FC), spin
      dipole (SD), and paramagnetic spin-orbit (PSO) terms that contribute to the
      hyperfine 1H and 13C NMR shifts of the individual atoms in the pyridine ligands
      and the spin-polarization effects in the ligand system that are linked to the
      character of the metal-ligand bond. The individual HF shielding terms are
      systematically discussed as they relate to the traditional, but somewhat mixed,
      contact and pseudocontact NMR contributions used extensively by experimental
      spectroscopists in biomolecular NMR and the development of PARACEST magnetic
      resonance contrast agents.

PMID- 29185728
TI  - Two-Dimensional Lead Halide Perovskites Templated by a Conjugated Asymmetric
      Diammonium.
AB  - We report novel two-dimensional lead halide perovskite structures templated by a
      unique conjugated aromatic dication, N,N-dimethylphenylene-p-diammonium (DPDA).
      The asymmetrically substituted primary and tertiary ammoniums in DPDA facilitate
      the formation of two-dimensional network (2DN) perovskite structures
      incorporating a conjugated dication between the PbX42- (X = Br, I) layers. These
      2DN structures of (DPDA)PbI4 and (DPDA)PbBr4 were characterized by single-crystal
      X-ray diffraction, showing uniquely low distortions in the Pb-X-Pb bond angle for
      2D perovskites. The Pb-I-Pb bond angle is very close to ideal (180 degrees ) for
      a 2DN lead iodide perovskite, which can be attributed to the ability of the rigid
      diammonium DPDA to insert into the PbX62- octahedral pockets. Optical
      characterization of (DPDA)PbI4 shows an excitonic absorption peak at 2.29 eV (541
      nm), which is red-shifted in comparison to similar 2DN lead iodide structures.
      Temperature-dependent photoluminescence of both compounds reveals both a self
      trapped exciton and free exciton emission feature. The reduced exciton absorption
      energy and emission properties are attributed to the dication-induced structural
      order of the inorganic PbX42- layers. DFT calculation results suggest mixing of
      the conjugated organic orbital component in the valence band of these 2DN
      perovskites. These results demonstrate a rational new strategy to incorporate
      conjugated organic dications into hybrid perovskites and will spur spectroscopic
      investigations of these compounds as well as optoelectronic applications.

PMID- 29185729
TI  - Si10Cu6N4 Cage Hexacoppersilsesquioxanes Containing N Ligands: Synthesis,
      Structure, and High Catalytic Activity in Peroxide Oxidations.
AB  - The synthesis, composition, and catalytic properties of a new family of
      hexanuclear Cu(II)-based phenylsilsesquioxanes are described here. Structural
      studies of 17 synthesized compounds revealed the general principle underlying
      their molecular topology: viz., a central metal oxide layer consisting of two Cu3
      trimers is coordinated by two cyclic [PhSiO1.5]5 siloxanolate ligands to form a
      skewed sandwich architecture with the composition [(PhSiO1.5)10(CuO)6]2+. In
      addition to this O ligation by the siloxanolate rings, two opposite copper ions
      are additionally coordinated by the nitrogen atoms of corresponding N ligand(s),
      such as 2,2'-bipyridine (compounds 1-9), 1,10-phenanthroline (compounds 10-13),
      mixed 1,10-phenanthroline/2,2'-bipyridine (compound 14), or bathophenanthroline
      (compounds 15-17). Finally, the charge balance is maintained by two HO-
      (compounds 1-7, 10-13, and 15-17), two H3CO- (compound 8), or two CH3COO-
      (compounds 9 and 14) anions. Complexes 1 and 10 exhibited a high activity in the
      oxidative amidation oxidation of alcohols. Compounds 1, 10, and 15 are very
      efficient homogeneous catalysts in the oxidation of alkanes and alcohols with
      peroxides.

PMID- 29185730
TI  - Understanding Poly(vinyl alcohol)-Mediated Ice Recrystallization Inhibition
      through Ice Adsorption Measurement and pH Effects.
AB  - The development of improved cryopreservative materials is necessary to enable
      complete recovery of living cells and tissue after frozen storage. Remarkably,
      poly(vinyl alcohol) (PVA) displays some of the same cryoprotective properties as
      many antifreeze proteins found in cold tolerant organisms. In particular, PVA is
      very effective at halting the Ostwald ripening of ice, a process that
      mechanically damages cells and tissue. Despite the large practical importance of
      such a property, the mechanism by which PVA interacts with ice is poorly
      understood, hindering the development of improved cryoprotective materials.
      Herein, we quantitatively evaluated ice growth kinetics in the presence of PVA at
      different pH conditions and in the presence of a range of neutral salts. We
      demonstrated that pH, but not salt identity, alters the ability of PVA to halt
      ice grain coarsening. These observations are consistent with hydrogen-bonding
      playing a crucial role in PVA-mediated ice recrystallization inhibition. The
      evolution of the size distribution of ice crystals with annealing was consistent
      with incomplete surface coverage of ice with PVA. Binding assay measurements of
      dissolved fluorescently labeled PVA in an ice slurry showed that PVA interacts
      with ice through weak adsorption (<9%) to the ice crystal surface, which stands
      in contrast to fluorescently tagged type III antifreeze peptide, which binds
      strongly (ca. 64%) under the same conditions.

PMID- 29185731
TI  - Silicone Wristband Passive Samplers Yield Highly Individualized Pesticide Residue
      Exposure Profiles.
AB  - Monitoring human exposure to pesticides and pesticide residues (PRs) remains
      crucial for informing public health policies, despite strict regulation of plant
      protection product and biocide use. We used 72 low-cost silicone wristbands as
      noninvasive passive samplers to assess cumulative 5-day exposure of 30
      individuals to polar PRs. Ethyl acetate extraction and LC-MS/MS analysis were
      used for the identification of PRs. Thirty-one PRs were detected of which 15 PRs
      (48%) were detected only in worn wristbands, not in environmental controls. The
      PRs included 16 fungicides (52%), 8 insecticides (26%), 2 herbicides (6%), 3
      pesticide derivatives (10%), 1 insect repellent (3%), and 1 pesticide synergist
      (3%). Five detected pesticides were not approved for plant protection use in the
      EU. Smoking and dietary habits that favor vegetable consumption were associated
      with higher numbers and higher cumulative concentrations of PRs in wristbands.
      Wristbands featured unique PR combinations. Our results suggest both environment
      and diet contributed to PR exposure in our study group. Silicone wristbands could
      serve as sensitive passive samplers to screen population-wide cumulative dietary
      and environmental exposure to authorized, unauthorized and banned pesticides.

PMID- 29185732
TI  - Efficient Energy Transfer from Near-Infrared Emitting Gold Nanoparticles to
      Pendant Ytterbium(III).
AB  - Here, we demonstrate efficient energy transfer from near-infrared-emitting ortho
      mercaptobenzoic acid-capped gold nanoparticles (AuNPs) to pendant ytterbium(III)
      cations. These functional materials combine the high molar absorptivity (1.21 *
      106 M-1 cm-1) and broad excitation features (throughout the UV and visible
      regions) of AuNPs with the narrow emissive properties of lanthanides. Interaction
      between the AuNP ligand shell and ytterbium is determined using both nuclear
      magnetic resonance and electron microscopy measurements. In order to identify the
      mechanism of this energy transfer process, the distance of the ytterbium(III)
      from the surface of the AuNPs is systematically modulated by changing the size of
      the ligand appended to the AuNP. By studying the energy transfer efficiency from
      the various AuNP conjugates to pendant ytterbium(III) cations, a Dexter-type
      energy transfer mechanism is suggested, which is an important consideration for
      applications ranging from catalysis to energy harvesting. Taken together, these
      experiments lay a foundation for the incorporation of emissive AuNPs in energy
      transfer systems.

PMID- 29185733
TI  - Gram-Scale Syntheses and Conductivities of [10]Cycloparaphenylene and Its
      Tetraalkoxy Derivatives.
AB  - [10]Cycloparaphenylene ([10]CPP) and its tetraalkoxy derivatives were synthesized
      on the gram scale in 7 steps starting from 1,4-benzoquinone or 2,5-dialkoxy-1,4
      benzoquinone. The key steps involve the highly cis-selective bis-addition of 4
      bromo-4'-lithiobiphenyl to the quinones to produce a five-ring unit containing
      cyclohexa-1,4-diene-3,6-diol moiety, the platinum-mediated dimerization of the
      five-ring unit, and the H2SnCl4-mediated reductive aromatization of
      cyclohexadienediol. The tetraalkoxy substituents increased the solubility of
      [10]CPP in common organic solvents. The carrier-transport properties of thin
      films of [10]CPP and its derivatives were measured for the first time and
      indicated that [10]CPP derivatives could rival phenyl-C61-butyric acid methyl
      ester, which is used widely as an n-type active layer in bulk heterojunction
      photovoltaics.

PMID- 29185734
TI  - Spatial Distribution and Seasonal Variation of Organophosphate Esters in Air
      above the Bohai and Yellow Seas, China.
AB  - Nine organophosphate esters (OPEs) were investigated in air samples collected
      over the Bohai and Yellow Seas (East Asia) during a research cruise between June
      28 and July 13, 2016. These same OPEs were quantified at a research site (North
      Huangcheng Island, NHI) in the middle of the Bohai Strait from May 16, 2015, to
      March 21, 2016. The median total OPE (SigmaOPE) concentration over the Bohai and
      Yellow Seas was 280 pg/m3. Tris(1-chloro-2-propyl) (TCPP) was the most abundant
      OPE, followed by tris(2-chloroethyl) phosphate (TCEP), tri-iso-butyl phosphate
      (TiBP), and tri-n-butyl phosphate (TnBP). Particle-bound OPEs accounted for 51 +/
      21% of the total OPEs. On NHI, the median SigmaOPE concentration was 210 pg/m3,
      and the average particle-bound fraction was 82 +/- 17%. For samples collected on
      NHI, significant negative linear correlations were found between the gaseous OPEs
      and 1/T (T: temperature (K)) (except TDCP, TPeP, and TCP). Among the 79
      investigated samples, significant correlations between the measured OPE
      gas/particle partitioning coefficients (Kp,m) and subcooled liquid pressure (PL?)
      (p < 0.05) were found for only 14 samples, suggesting that OPEs have low
      potential to achieve equilibrium or ascribe to the artificial sampling. The
      annual dry deposition input of OPEs into the Bohai and Yellow Seas is estimated
      to be 12 tons/year.

PMID- 29185735
TI  - Tunable Emission of Iridium(III) Complexes Bearing Sulfur-Bridged Dipyridyl
      Ligands.
AB  - A series of six new cyclometalated iridium(III) complexes [Ir(ppy)2(N?N)][PF6]
      (ppy = 2-phenylpyridine) is reported herein. Proligands bis(pyridin-2-yl)sulfane
      (1a), 2,2'-sulfinyldipyridine (1b), 2,2'-sulfonyldipyridine (1c), bis(4
      methylpyridin-2-yl)sulfane (2a), 2,2'-sulfinylbis(4-methylpyridine) (2b), and
      2,2'-sulfonylbis(4-methylpyridine) (2c) were synthesized, characterized, and
      employed as the N?N ancillary ligand. Changing the oxidation state of the sulfur
      atom serves as a switch to alter the emissive state from that of mainly 3LC
      character (blue-green emission) to one of 3MLCT/3LLCT character (yellow
      emission). Sulfide and sulfoxide complexes Ir(1a), Ir(1b), Ir(2a), and Ir(2b)
      show identical, vibrationally structured emission profiles with maxima at 478,
      510, 548 nm in CH2Cl2 solutions resulting from a 3LC state. In contrast, sulfone
      complexes Ir(1c) and Ir(2c) show broad, red-shifted 3CT emission (552 and 537 nm,
      respectively).

PMID- 29185736
TI  - Enhancing Fatty Acid Production of Saccharomyces cerevisiae as an Animal Feed
      Supplement.
AB  - Saccharomyces cerevisiae is used for edible purposes, such as human food or as an
      animal feed supplement. Fatty acids are also beneficial as feed supplements, but
      S. cerevisiae produces small amounts of fatty acids. In this study, we enhanced
      fatty acid production of S. cerevisiae by overexpressing acetyl-CoA carboxylase,
      thioesterase, and malic enzyme associated with fatty acid metabolism. The
      enhanced strain pAMT showed 2.4-fold higher fatty acids than the wild-type
      strain. To further increase the fatty acids, various nitrogen sources were
      analyzed and calcium nitrate was selected as an optimal nitrogen source for fatty
      acid production. By concentration optimization, 672 mg/L of fatty acids was
      produced, which was 4.7-fold higher than wild-type strain. These results
      complement the low level fatty acid production and make it possible to obtain the
      benefits of fatty acids as an animal feed supplement while, simultaneously,
      maintaining the advantages of S. cerevisiae.

PMID- 29185737
TI  - Parallel Tempering of Dark Matter from the Ebola Virus Proteome: Comparison of
      CHARMM36m and CHARMM22 Force Fields with Implicit Solvent.
AB  - Intrinsically disordered proteins are characterized by their large manifold of
      thermally accessible conformations and their related statistical weights, making
      them an interesting target of simulation studies. To assess the development of a
      computational framework for modeling this distinct class of proteins, this work
      examines temperature-based replica-exchange simulations to generate a
      conformational ensemble of a 28-residue peptide from the Ebola virus protein
      VP35. Starting from a prefolded helix-beta-turn-helix topology observed in a
      crystallographic assembly, the simulation strategy tested is the recently refined
      CHARMM36m force field combined with a generalized Born solvent model. A
      comparison of two replica-exchange methods is provided, where one is a
      traditional approach with a fixed set of temperatures and the other is an
      adaptive scheme in which the thermal windows are allowed to move in temperature
      space. The assessment is further extended to include a comparison with equivalent
      CHARMM22 simulation data sets. The analysis finds CHARMM36m to shift the minimum
      in the potential of mean force (PMF) to a lower fractional helicity compared with
      CHARMM22, while the latter showed greater conformational plasticity along the
      helix-forming reaction coordinate. Among the simulation models, only the adaptive
      tempering method with CHARMM36m found an ensemble of conformational heterogeneity
      consisting of transitions between alpha-helix-beta-hairpin folds and unstructured
      states that produced a PMF of fractional fold propensity in qualitative agreement
      with circular dichroism experiments reporting a disordered peptide.

PMID- 29185738
TI  - Oxazole-Containing Diterpenoids from Cell Cultures of Salvia miltiorrhiza and
      Their Anti-HIV-1 Activities.
AB  - Four new oxazole-containing diterpenoids, salvianans A-D (1-4), along with three
      known diterpenoids (5-7), were isolated from Salvia miltiorrhiza cell cultures.
      The structures of the new compounds were elucidated using spectroscopic methods
      and single-crystal X-ray diffraction. The evaluation for their anti-HIV-1
      activities revealed that 2 and 3 displayed inhibitory activities with IC50 values
      of 0.03 and 1.2 MUM, respectively. The time of addition (TOA) assay and long
      terminal repeat (LTR) luciferase reporter assay results indicated that compound 2
      was an HIV-1 transcription inhibitor and might be a lead compound of antiviral
      agents acting on HIV-1 transcription.

PMID- 29185739
TI  - B-N Lewis Pair Functionalization of Anthracene: Structural Dynamics,
      Optoelectronic Properties, and O2 Sensitization.
AB  - The judicial placement of main group elements in conjugated structures is
      emerging as a key route to novel functional hybrid materials. We demonstrate here
      that the formation of B-N Lewis pairs at the periphery of anthracene leads to
      buckling of the backbone while also dramatically lowering the LUMO energy. The
      resulting BN-substituted contorted polycyclic aromatic hydrocarbons show large
      bathochromic shifts in the absorption and emission relative to all-carbon
      analogs. In the presence of light, they rapidly react with O2 without the need
      for an external photosensitizer, resulting in selective and reversible formation
      of the corresponding endoperoxides.

PMID- 29185741
TI  - Effective Polarizability Models.
AB  - Theories for the effective polarizability of a small particle in a medium are
      presented using different levels of approximation: we consider the virtual
      cavity, real cavity, and the hard-sphere models as well as a continuous
      interpolation of the latter two. We present the respective hard-sphere and cavity
      radii as obtained from density-functional simulations as well as the resulting
      effective polarizabilities at discrete Matsubara frequencies. This enables us to
      account for macroscopic media in van der Waals interactions between molecules in
      water and their Casimir-Polder interaction with an interface.

PMID- 29185740
TI  - Single-Molecule Fluorescence Reveals Commonalities and Distinctions among Natural
      and in Vitro-Selected RNA Tertiary Motifs in a Multistep Folding Pathway.
AB  - Decades of study of the RNA folding problem have revealed that diverse and
      complex structured RNAs are built from a common set of recurring structural
      motifs, leading to the perspective that a generalizable model of RNA folding may
      be developed from understanding of the folding properties of individual
      structural motifs. We used single-molecule fluorescence to dissect the kinetic
      and thermodynamic properties of a set of variants of a common tertiary structural
      motif, the tetraloop/tetraloop-receptor (TL/TLR). Our results revealed a
      multistep TL/TLR folding pathway in which preorganization of the ubiquitous AA
      platform submotif precedes the formation of the docking transition state and
      tertiary A-minor hydrogen bond interactions form after the docking transition
      state. Differences in ion dependences between TL/TLR variants indicated the
      occurrence of sequence-dependent conformational rearrangements prior to and after
      the formation of the docking transition state. Nevertheless, varying the junction
      connecting the TL/TLR produced a common kinetic and ionic effect for all
      variants, suggesting that the global conformational search and compaction
      electrostatics are energetically independent from the formation of the tertiary
      motif contacts. We also found that in vitro-selected variants, despite their
      similar stability at high Mg2+ concentrations, are considerably less stable than
      natural variants under near-physiological ionic conditions, and the occurrence of
      the TL/TLR sequence variants in Nature correlates with their thermodynamic
      stability in isolation. Overall, our findings are consistent with modular but
      complex energetic properties of RNA structural motifs and will aid in the
      eventual quantitative description of RNA folding from its secondary and tertiary
      structural elements.

PMID- 29185742
TI  - Isolable Borane-Based Diradical and Triradical Fused by a Diamagnetic Transition
      Metal Ion.
AB  - Complex Fe(bpyB)3 (1, bpyB = 5,5'-bis(dimesitylboranyl)-2,2'-bipyridine) and its
      reduced species [(18-c-6)K(THF)2].[Fe(bpyB)3] (2) were synthesized. Their solid
      state and electronic structures were investigated by single crystal X-ray
      crystallography, electron paramagnetic resonance and UV-vis spectroscopy, and
      SQUID measurements. In 1 two bpyB radical anions are fused by a diamagnetic FeII
      ion, whereas in 2 all three bpyB ligands are in the radical state. Complex 1
      possesses an open-shell singlet ground state with a singlet-triplet gap of 0.18
      kcal mol-1 and 2 features an open-shell doublet ground state with a doublet
      quartet gap of 1.4 kcal mol-1, as determined by SQUID measurements. The unpaired
      electrons in 1 and 2 mainly delocalize over the boron atoms and the bipyrdine
      moieties with negligible spin density at the iron center. Complex 2 represents
      the first isolable example of boron-based triradicals.

PMID- 29185743
TI  - Determination of the Absolute Configuration of Polyhydroxy Compound Ostreol B
      Isolated from the Dinoflagellate Ostreopsis cf. ovata.
AB  - Following isolation of the polyhydroxy compound, ostreol B, from cultivated cells
      of the toxic dinoflagellate Ostreopsis cf. ovata collected in South Korea, 1D and
      2D NMR spectroscopy were employed to determine the planar chemical structure of
      this compound, which contained a tetrahydropyran ring, two terminal double bonds,
      and 21 hydroxyl groups. The absolute configurations of all stereogenic carbon
      centers in ostreol B were then determined through a combination of the J-based
      configuration analysis, rotating frame Overhauser effect correlations, and the
      modified Mosher method following cleavage of the 1,2-diol bonds. Ostreol B was
      also found to exhibit moderate cytotoxicity in HepG2, Neuro-2a and HCT-116 cells.

PMID- 29185744
TI  - On the Origin of Ionic Rectification in DNA-Stuffed Nanopores: The Breaking and
      Retrieving Symmetry.
AB  - The discovery of ionic current rectification (ICR) phenomena in synthetic
      nanofluidic systems elicits broad interest from interdisciplinary fields of
      chemistry, physics, materials science, and nanotechnology; and thus, boosts their
      applications in, for example, chemical sensing, fluidic pumping, and energy
      related aspects. So far, it is generally accepted that the ICR effect stems from
      the broken symmetry either in the nanofluidic structures, or in the environmental
      conditions. Although this empirical regularity is supported by numerous
      experimental and theoretical results, great challenge still remains to precisely
      figure out the correlation between the asymmetric ion transport properties and
      the degree of symmetry breaking. An appropriate and quantified measure is
      therefore highly demanded. Herein, taking DNA-stuffed nanopores as a model
      system, we systematically investigate the evolution of dynamic ICR in between two
      symmetric states. The fully stuffed and fully opened nanopores are symmetric;
      therefore, they exhibit linear ion transport behaviors. Once the stuffed DNA
      superstructures are asymmetrically removed from one end of the nanopore via
      aptamer-target interaction, the nanofluidic system becomes asymmetric and starts
      to rectify ionic current. The peak of ICR is found right before the breakthrough
      of the stuffed DNA forest. After that, the nanofluidic system gradually retrieves
      symmetry, and becomes non-rectified. Theoretical results by both the coarse
      grained Poisson-Nernst-Planck model and the 1D statistic model excellently
      support the experimental observations, and further establish a quantified
      correlation between the ICR effect and the degree of asymmetry for different
      molecular filling configurations. Based on the ICR properties, we develop a proof
      of-concept demonstration for sensing ATP, termed the ATP balance. These findings
      help to clarify the origin of ICR, and show implications to other asymmetric
      transport phenomena for future innovative nanofluidic devices and materials.

PMID- 29185745
TI  - Biosynthesis of Neokestose Laurate Catalyzed by Candida antarctica Lipase B and
      Its Antimicrobial Activity against Food Pathogenic and Spoilage Bacteria.
AB  - To increase the functionality and broaden the potential application of
      neokestose, neokestose laurate was biosynthesized using Candida antarctica lipase
      B as biocatalyst, for which a mixture of 20% DMSO in 2-methyl-2-butanol (v/v) was
      chosen as the reaction medium. The optimum conditions for biosynthesis were as
      follows: a molar ratio of vinyl laurate to neokestose of 12, a temperature of 50 
      degrees C, molecular sieves of 100 g/L, and enzyme loading of 10 g/L. Under the
      optimal conditions, the conversion rate was achieved over 80%. The synthesized
      chemical 6'-O-lauroylneokestose confirmed by nuclear magnetic resonance (NMR)
      exhibited good emulsification with critical micelle concentration (CMC) of 352
      MUM and broad antibacterial activity against Gram-positive bacteria such as
      Staphylococcus aureus, Listeria monocytogenes, Streptococcus mutans, Bacillus
      subtilis, and Bacillus cereus. Conclusively, 6'-O-lauroylneokestose was evidenced
      to be a dual-functional agent with emulsification and antibacterial activity,
      showing promising application potential in the food industry.

PMID- 29185746
TI  - Novel Aryl Substituted Pyrazoles as Small Molecule Inhibitors of Cytochrome P450
      CYP121A1: Synthesis and Antimycobacterial Evaluation.
AB  - Three series of biarylpyrazole imidazole and triazoles are described, which vary
      in the linker between the biaryl pyrazole and imidazole/triazole group. The
      imidazole and triazole series with the short -CH2- linker displayed promising
      antimycobacterial activity, with the imidazole-CH2- series (7) showing low MIC
      values (6.25-25 MUg/mL), which was also influenced by lipophilicity. Extending
      the linker to -C(O)NH(CH2)2- resulted in a loss of antimycobacterial activity.
      The binding affinity of the compounds with CYP121A1 was determined by UV-visible
      optical titrations with KD values of 2.63, 35.6, and 290 MUM, respectively, for
      the tightest binding compounds 7e, 8b, and 13d from their respective series. Both
      binding affinity assays and docking studies of the CYP121A1 inhibitors suggest
      type II indirect binding through interstitial water molecules, with key binding
      residues Thr77, Val78, Val82, Val83, Met86, Ser237, Gln385, and Arg386,
      comparable with the binding interactions observed with fluconazole and the
      natural substrate dicyclotyrosine.

PMID- 29185747
TI  - Aluminabenzene-Rh and -Ir Complexes: Synthesis, Structure, and Application toward
      Catalytic C-H Borylation.
AB  - Aluminabenzene-rhodium and -iridium complexes were synthesized, in which the
      aluminum atom played as a proximal Lewis acidic site. Based on their structural
      analysis, aluminabenzene ligand could coordinate to Rh and Ir as a eta5
      pentadienyl ligand. The Lewis acidic character of aluminum atom in aluminabenzene
      ligand was confirmed by treatment with 4-dimethylaminopyridine to form the
      corresponding Lewis acid-base complexes. In addition, the alpha-selective C-H
      borylation of triethylamine with the aluminabenzene-ligated iridium catalyst was
      demonstrated.

PMID- 29185748
TI  - 4-Aminoquinoline Antimalarials Containing a Benzylmethylpyridylmethylamine Group
      Are Active against Drug Resistant Plasmodium falciparum and Exhibit Oral Activity
      in Mice.
AB  - Emergence of drug resistant Plasmodium falciparum including artemisinin-tolerant
      parasites highlights the need for new antimalarials. We have previously shown
      that dibemequines, 4-amino-7-chloroquinolines with dibenzylmethylamine
      (dibemethin) side chains, are efficacious. In this study, analogues in which the
      terminal phenyl group of the dibemethin was replaced with a 2-pyridyl group and
      in which the 4-amino-7-chloroquinoline was either maintained or replaced with a 4
      aminoquinoline-7-carbonitrile were synthesized in an effort to improve
      druglikeness. These compounds exhibited significantly improved solubility and
      decreased lipophilicity and were potent against chloroquine-sensitive (NF54) and 
      resistant (Dd2 and 7G8) P. falciparum strains with 5/6 having IC50 < 100 nM
      against the NF54 strain. All inhibited both beta-hematin (synthetic hemozoin)
      formation and hemozoin formation in the parasite. Parasitemia was reduced by over
      90% in P. berghei infected mice in 3/6 derivatives following oral dosing at 4 *
      30 mg/kg, with microsomal metabolic stability data suggesting that this could be
      attributed to highly active metabolites.

PMID- 29185749
TI  - Energy Transfer to the Hydrogen Bond in the (H2O)2 + H2O Collision.
AB  - Trajectory procedures are used to study the collision between the vibrationally
      excited H2O and the ground-state (H2O)2 with particular reference to energy
      transfer to the hydrogen bond through the inter- and intramolecular pathways. In
      nearly 98% of the trajectories, energy transfer processes occur on a
      subpicosecond scale (<=0.7 ps). The H2O transfers approximately three-quarters of
      its excitation energy to the OH stretches of the dimer. The first step of the
      intramolecular pathway in the dimer involves a near-resonant first overtone
      transition from the OH stretch to the bending mode. The energy transfer
      probability in the presence of the 1:2 resonance is 0.61 at 300 K. The bending
      mode then redistributes its energy to low-frequency intermolecular vibrations in
      a series of small excitation steps, with the pathway which results in the
      hydrogen-bonding modes gaining most of the available energy. The hydrogen bonding
      in ~50% of the trajectories ruptures on vibrational excitation, leaving one
      quantum in the bend of the monomer fragment. In a small fraction of trajectories,
      the duration of collision is longer than 1 ps, during which the dimer and H2O
      form a short-lived complex through a secondary hydrogen bond, which undergoes
      large amplitude oscillations.

PMID- 29185750
TI  - Carbon Dots-Plasmonics Coupling Enables Energy Transfer and Provides Unique
      Chemical Signatures.
AB  - Plasmonic nanostructures and carbon dots (C-dots) are fascinating optical
      materials, utilized in imaging, sensing, and color generation. Interaction
      between plasmonic materials and C-dots may lead to new hybrid materials with
      controllable optical properties. Herein, we demonstrate for the first time
      coupling between plasmonic modes and C-dots deposited upon a plasmonic silver
      hole array. The coupling leads to a remarkable visual attenuation and shifts of
      the plasmonic wavelengths (i.e., color tuning). In particular, the C-dots-plasmon
      couplings and pertinent color transformations depend both upon the C-dots'
      fluorescence emission wavelengths and functional residues displayed upon the C
      dots' surface. This optical modulation corresponds to energy level alignment and
      consequent energy transfer between the C-dots and the plasmonic silver hole
      array. Notably, the energy coupling observed in the C-dot-plasmonic hybrid system
      allows distinguishing between C-dots species exhibiting similar optical
      properties, albeit displaying different functional residues.

PMID- 29185751
TI  - Ca2+-Switchable Glucose Dehydrogenase Associated with Electrochemical/Electronic
      Interfaces: Applications to Signal-Controlled Power Production and Biomolecular
      Release.
AB  - An artificial Ca2+-regulated PQQ glucose dehydrogenase (PQQ-GDH) enzyme was
      electrically connected to conducting electrodes and semiconductor interfaces.
      Direct electron transfer from the enzyme to the conducting electrode support was
      stimulated by the addition of Ca2+ cations resulting in reversible enzyme
      activation. A signal-switchable biofuel cell and biomolecular release have been
      realized using the Ca2+-activated enzyme immobilized on conducting electrodes.
      Interfacing the signal-switchable enzyme with a semiconductor chip allowed
      electronic read out of the enzyme ON-OFF states. The developed approach based on
      the signal-regulated PQQ-GDH enables numerous bioelectrochemical/bioelectronic
      applications of the developed systems in signal-activated biosensors and biofuel
      cells, as well as in biomolecular computing/logic systems.

PMID- 29185752
TI  - Hydrogenation Facilitates Proton Transfer through Two-Dimensional Honeycomb
      Crystals.
AB  - Recent experiments have triggered a debate about the ability of protons to
      transfer easily through individual layers of graphene and hexagonal boron nitride
      (h-BN). However, state-of-the-art computer calculations have shown that the
      barriers to proton penetration can, at >3 eV, be excessively high. Despite
      considerable interest the origin of this apparent anomaly between experiment and
      simulation remains unclear. We offer a new perspective on this debate and show on
      the basis of first-principles calculations that the barrier for proton
      penetration is significantly reduced, to <1 eV, upon hydrogenation, even in the
      absence of pinholes in the lattice. Although hydrogenation has not been offered
      as an explanation before, analysis reveals that the barrier is reduced because
      hydrogenation destabilizes the initial state (a deep-lying chemisorption state)
      and expands the honeycomb lattice through which the protons penetrate. This study
      offers a rationalization of the fast proton transfer observed in experiments and
      highlights the ability of proton transport through single-layer materials in
      hydrogen-rich solutions.

PMID- 29185753
TI  - Density Functional Computations and Molecular Dynamics Simulations of the
      Triethylammonium Triflate Protic Ionic Liquid.
AB  - Systematic molecular dynamics simulations based on an empirical force field have
      been carried out for samples of triethylammonium trifluoromethanesulfonate
      (triethylammonium triflate, [TEA][Tf]), covering a wide temperature range 200 K
      <= T <= 400 K and analyzing a broad set of properties, from self-diffusion and
      electrical conductivity to rotational relaxation and hydrogen-bond dynamics. The
      study is motivated by recent quasi-elastic neutron scattering and differential
      scanning calorimetry measurements on the same system, revealing two successive
      first order transitions at T ~ 230 and 310 K (on heating), as well as an
      intriguing and partly unexplained variety of subdiffusive motions of the acidic
      proton. Simulations show a weakly discontinuous transition at T = 310 K and
      highlight an anomaly at T = 260 K in the rotational relaxation of ions that we
      identify with the simulation analogue of the experimental transition at T = 230
      K. Thus, simulations help identifying the nature of the experimental transitions,
      confirming that the highest temperature one corresponds to melting, while the one
      taking place at lower T is a transition from the crystal, stable at T <= 260 K,
      to a plastic phase (260 <= T <= 310 K), in which molecules are able to rotate
      without diffusing. Rotations, in particular, account for the subdiffusive motion
      seen at intermediate T both in the experiments and in the simulation. The
      structure, distribution, and strength of hydrogen bonds are investigated by
      molecular dynamics and by density functional computations. Clustering of ions of
      the same sign and the effect of contamination by water at 1% wgt concentration
      are discussed as well.

PMID- 29185754
TI  - Defects Cause Subgap Luminescence from a Crystalline Tetracene Derivative.
AB  - We use steady-state and ultrafast nonlinear spectroscopies in combination with
      density functional theory calculations to explain light emission below the
      optical gap energy (Eo) of crystalline samples of 5,12-diphenyl tetracene (DPT).
      In particular, the properties of vibrational coherences imprinted on a probe
      pulse transmitted through a DPT single crystal indicate discrete electronic
      transitions below Eo of this organic semiconductor. Analysis of coherence spectra
      leads us to propose structural defect states give rise to these discrete
      transitions and subgap light emission. We use the polarization dependence of
      vibrational coherence spectra to tentatively assign these defects in our DPT
      samples. Our results provide fundamental insights into the properties of midgap
      states in organic materials important for their application in next-generation
      photonics and optoelectronics technologies.

PMID- 29185755
TI  - VDAC1 and SERCA3 Mediate Progesterone-Triggered Ca2+ Signaling in Breast Cancer
      Cells.
AB  - Progesterone is a biphasic hormone whose confounding role in breast cancer cells
      involves an initial proliferative surge, followed by sustained growth arrest.
      Recently we reported that progesterone induces a time- and concentration
      dependent release of reactive oxygen species and thus regulates the
      antiproliferative activity in the breast cancer cell line. Furthermore, the
      expression of p27, a crucial cell cycle control protein, was regulated by binding
      of progesterone on progesterone receptor B, thus leading to antiproliferative
      signaling via multiple signaling pathways including p53, PTEN, and antioxidant
      systems. Here, we performed an LC-MS/MS analysis of three different breast cancer
      cell lines. Bioinformatics data analysis and functional classification of
      proteins revealed a role of progesterone in calcium signaling in MCF-7 cells, and
      the major differentially expressed calcium regulators were S100A11, S100A10,
      calreticulin, VDAC1, SERCA3, and SERCA1. Later on we confirmed it by a cell-line
      based system having a calcium cameleon sensor targeted at endoplasmic reticulum
      and found moderate calcium efflux from endoplasmic reticulum upon progesterone
      treatment. Real-time PCR, Western blot, and TMRM staining confirmed the role of
      calcium signaling regulators VDAC1 and SERCA3 in progesterone response. Taking
      together all of these results with our previous studies, we suggest that
      progesterone, by regulating important proteins involved in calcium signaling and
      transport, can modulate cell proliferation and cell death. Furthermore, our
      research may open new avenues for the hypothesis that surgery conducted during
      the luteal phase of the menstrual cycle might facilitate improved patient
      survival.

PMID- 29185756
TI  - Supramolecular Polymerization of N,N',N",N'''-tetra-(Tetradecyl)-1,3,6,8
      pyrenetetracarboxamide: A Computational Study.
AB  - The role of molecular dipole orientations and intermolecular interactions in a
      derivative of pyrene on its supramolecular self-assembly in solution has been
      investigated using quantum chemical and force field based computational
      approaches. Five possible dipole configurations of the molecule have been
      examined, among which the one in which adjacent dipole vectors are antiparallel
      to each other is determined to be the ground state, on electrostatic grounds.
      Self-assembly of this molecule under realistic conditions has been studied using
      MD simulations. Dipolar relaxation in its liquid crystalline (LC) phase has been
      investigated and contrasted against that in the well-established benzene-1,3,5
      tricarboxamide (BTA) family. The dihedral barrier related to the amide dipole
      flip is larger in the pyrene system than in BTA which explains the differences in
      their dipolar relaxation behaviors. The mechanism underlying polarization
      switching upon the application of an external electric field in the LC phase is
      investigated. Unlike in BTA, this switching is not associated with a reversal of
      the helical sense of the hydrogen bonded chains, due to differences in molecular
      symmetry. The observations enable general conclusions on the relationship between
      electric field induced chiral enhancement and symmetry to be drawn.

PMID- 29185757
TI  - Quantum Redirection of Antenna Absorption to Photosynthetic Reaction Centers.
AB  - The early steps of photosynthesis involve the photoexcitation of reaction centers
      (RCs) and light-harvesting (LH) units. Here, we show that the historically
      overlooked excitonic delocalization across RC and LH pigments results in a
      redistribution of absorption amplitudes that benefits the absorption cross
      section of the optical bands associated with the RC of several species. While we
      prove that this redistribution is robust to the microscopic details of the
      dephasing between these units in the purple bacterium Rhodospirillum rubrum, we
      are able to show that the redistribution witnesses a more fragile, but
      persistent, coherent population dynamics which directs excitations from the LH
      toward the RC units under incoherent illumination and physiological conditions.
      Even though the redirection does not seem to affect importantly the overall
      efficiency in photosynthesis, stochastic optimization allows us to delineate
      clear guidelines and develop simple analytic expressions in order to amplify the
      coherent redirection in artificial nanostructures.

PMID- 29185758
TI  - pH-Dependent Singlet O2 Oxidation Kinetics of Guanine and 9-Methylguanine: An
      Online Mass Spectrometry and Spectroscopy Study Combined with Theoretical
      Exploration.
AB  - We report a kinetic and mechanistic study on the title reactions, in which 1O2
      was generated by the reaction of H2O2 with Cl2 and bubbled into an aqueous
      solution of guanine and 9-methylguanine (9MG) at different pH values. Oxidation
      kinetics and product branching ratios were measured using online electrospray
      ionization mass spectrometry coupled with absorption and emission
      spectrophotometry, and product structures were determined by collision-induced
      dissociation (CID) tandem mass spectrometry. Experiments revealed strong pH
      dependence of the reactions. The oxidation of guanine is noticeable only in basic
      solution, while the oxidation of 9MG is weak in acidic solution, increases in
      neutral solution, and becomes intensive in basic solution. 5-Guanidinohydantoin
      (Gh) and spiroiminodihydantoin (Sp) were detected as the major oxidation products
      of guanine and 9MG, and Sp became dominant in basic solution. A reaction
      intermediate was captured in mass spectra, and assigned to gem-diol on the basis
      of CID measurements. This intermediate served as the precursor for the formation
      of Gh. After taking into account solution compositions at each pH, first-order
      oxidation rate constants were extracted for individual species: that is, 3.2-3.6
      * 107 M-1 s-1 for deprotonated guanine, and 1.2 * 106 and 4.6-4.9 * 107 M-1 s-1
      for neutral and deprotonated 9MG, respectively. Guided by approximately spin
      projected density-functional-theory-calculated reaction potential energy
      surfaces, the kinetics for the initial 1O2 addition to guanine and 9MG was
      evaluated using transition state theory (TST). The comparison between TST
      modeling and experiment confirms that 1O2 addition is rate-limiting for
      oxidation, which forms endoperoxide and peroxide intermediates as determined in
      previous measurements of the same systems in the gas phase.

PMID- 29185759
TI  - Electrocatalytic Dehydrogenative Esterification of Aliphatic Carboxylic Acids:
      Access to Bioactive Lactones.
AB  - A scalable and efficient electrocatalytic dehydrogenative esterification is
      reported. With an indirect electrolysis strategy, both intra- and intermolecular
      type reactions were amenable to this practical method. With n-Bu4NI as the
      catalyst, undesired decarboxylation and Baeyer-Villiger oxidation were
      suppressed. More importantly, this novel method provided reliable and direct
      access to the natural product cytosporanone A on a gram scale.

PMID- 29185760
TI  - Heterogeneous Kinetics in the Functionalization of Single Plasmonic
      Nanoparticles.
AB  - The functionalization of gold nanoparticles with DNA has been studied extensively
      in solution; however, these ensemble measurements do not reveal particle-to
      particle differences. Here we study the functionalization of gold nanorods with
      thiolated single-stranded DNA (ssDNA) at the single-particle level. We exploit
      the sensitivity of the plasmon resonance to the local refractive index to study
      the functionalization in real time using single-particle spectroscopy. We find
      particle-to-particle variations of the plasmon shift that are attributed to the
      particle size distribution and variations in ssDNA coverage. We find that the
      ssDNA coverage varies by ~10% from particle to particle, beyond the expected
      variation due to Poisson statistics. Surprisingly, we find binding rates that
      differ from particle to particle by an order of magnitude, even though the buffer
      conditions are identical. We ascribe this heterogeneity to a distribution of
      activation energies caused by particle-to-particle variations in effective
      surface charge. These results yield insight into the kinetics of
      biofunctionalization at the single particle level and highlight that significant
      kinetic heterogeneity has to be taken into account in applications of functional
      particles. The presented methodology is easily extended to any nanoparticle
      coating and can be used to optimize functionalization protocols.

PMID- 29185761
TI  - Synthesis of the Cancer-Associated KH-1 Antigen by Block Assembly of Its Backbone
      Structure Followed by One-Step Grafting of Three Fucose Residues.
AB  - A robust, convergent, and efficient strategy was developed for the synthesis of
      the nonasaccharide cancer antigen KH-1. This strategy featured a one-pot block
      assembly of the linear hexasaccharide backbone using three disaccharides followed
      by grafting of three fucose residues onto the backbone in one step.

PMID- 29185763
TI  - Enhanced Electron Mobility in Nonplanar Tensile Strained Si Epitaxially Grown on
      SixGe1-x Nanowires.
AB  - We report the growth and characterization of epitaxial, coherently strained
      SixGe1-x-Si core-shell nanowire heterostructure through vapor-liquid-solid growth
      mechanism for the SixGe1-x core, followed by an in situ ultrahigh-vacuum chemical
      vapor deposition for the Si shell. Raman spectra acquired from individual
      nanowire reveal the Si-Si, Si-Ge, and Ge-Ge modes of the SixGe1-x core and the Si
      Si mode of the shell. Because of the compressive (tensile) strain induced by
      lattice mismatch, the core (shell) Raman modes are blue (red) shifted compared to
      those of unstrained bare SixGe1-x (Si) nanowires, in good agreement with values
      calculated using continuum elasticity model coupled with lattice dynamic theory.
      A large tensile strain of up to 2.3% is achieved in the Si shell, which is
      expected to provide quantum confinement for electrons due to a positive core-to
      shell conduction band offset. We demonstrate n-type metal-oxide-semiconductor
      field-effect transistors using SixGe1-x-Si core-shell nanowires as channel and
      observe a 40% enhancement of the average electron mobility compared to control
      devices using Si nanowires due to an increased electron mobility in the tensile
      strained Si shell.

PMID- 29185762
TI  - Impacts of Future European Emission Reductions on Aerosol Particle Number
      Concentrations Accounting for Effects of Ammonia, Amines, and Organic Species.
AB  - Although they are currently unregulated, atmospheric ultrafine particles (<100
      nm) pose health risks because of, e.g., their capability to penetrate deep into
      the respiratory system. Ultrafine particles, often minor contributors to
      atmospheric particulate mass, typically dominate aerosol particle number
      concentrations. We simulated the response of particle number concentrations over
      Europe to recent estimates of future emission reductions of aerosol particles and
      their precursors. We used the chemical transport model PMCAMx-UF, with novel
      updates including state-of-the-art descriptions of ammonia and dimethylamine new
      particle formation (NPF) pathways and the condensation of organic compounds onto
      particles. These processes had notable impacts on atmospheric particle number
      concentrations. All three emission scenarios (current legislation, optimized
      emissions, and maximum technically feasible reductions) resulted in substantial
      (10-50%) decreases in median particle number concentrations over Europe.
      Consistent reductions were predicted in Central Europe, while Northern Europe
      exhibited smaller reductions or even increased concentrations. Motivated by the
      improved NPF descriptions for ammonia and methylamines, we placed special focus
      on the potential to improve air quality by reducing agricultural emissions, which
      are a major source of these species. Agricultural emission controls showed
      promise in reducing ultrafine particle number concentrations, although the change
      is nonlinear with particle size.

PMID- 29185764
TI  - Highly Efficient Photoelectrochemical Water Splitting from Hierarchical WO3/BiVO4
      Nanoporous Sphere Arrays.
AB  - Nanoarchitecture of bismuth vanadate (BiVO4) photoanodes for effectively
      increasing light harvesting efficiency and simultaneously achieving high charge
      separation efficiency is the key to approaching their theoretic performance of
      solar-driven water splitting. Here, we developed hierarchical BiVO4 nanoporous
      sphere arrays, which are composed of small nanoparticles and sufficient voids for
      offering high capability of charge separation. Significantly, multiple light
      scattering in the sphere arrays and voids along with the large effective
      thickness of the BiVO4 photoanode induce efficient light harvesting. In addition,
      attributed to ultrathin two-dimensional Bi2WO6 nanosheets as the precursor, the
      synergy of various enhancement strategies including WO3/BiVO4 nanojunction
      formation, W-doping, and oxygen vacancy creation can be directly incorporated
      into such a unique hierarchical architecture during the one-step synthesis of
      BiVO4 without complex pre- or post-treatment. The as-obtained photoanode exhibits
      a water splitting photocurrent of 5.5 mA cm-2 at 1.23 V versus RHE under 1-sun
      illumination, among the best values reported up-to-date in the field.

PMID- 29185765
TI  - Designing Diameter-Modulated Heterostructure Nanowires of PbTe/Te by Controlled
      Dewetting.
AB  - Heterostructures consisting of semiconductors with controlled morphology and
      interfaces find applications in many fields. A range of axial, radial, and
      diameter-modulated nanostructures have been synthesized primarily using vapor
      phase methods. Here, we present a simple wet chemical routine to synthesize
      heterostructures of PbTe/Te using Te nanowires as templates. A morphology
      evolution study for the formation of these heterostructures has been performed.
      On the basis of these control experiments, a pathway for the formation of these
      nanostructures is proposed. Reduction of a Pb precursor to Pb on Te nanowire
      templates followed by interdiffusion of Pb/Te leads to the formation of a thin
      shell of PbTe on the Te wires. Controlled dewetting of the thin shell leads to
      the formation of cube-shaped PbTe that is periodically arranged on the Te wires.
      Using control experiments, we show that different reactions parameters like rate
      of addition of the reducing agent, concentration of Pb precursor and thickness of
      initial Te nanowire play a critical role in controlling the spacing between the
      PbTe cubes on the Te wires. Using simple surface energy arguments, we propose a
      mechanism for the formation of the hybrid. The principles presented are general
      and can be exploited for the synthesis of other nanoscale heterostructures.

PMID- 29185766
TI  - Molecular-Iodine-Catalyzed Cyclization of 2-Alkynylanilines via Iodocyclization
      Protodeiodination Sequence.
AB  - Molecular iodine catalyzes a cyclization of N-aryl-2-alkynylanilines, which
      proceeds through the iodocyclization of 2-alkynylanilines followed by the
      protodeiodination of the iodocyclized intermediates at room temperature.
      Furthermore, the molecular iodine catalysis can be applied to the cascade
      cyclization of 2-(enynyl)aniline and to the tandem cyclization-addition reaction
      of 2-alkynylanilines with alpha,beta-enones.

PMID- 29185767
TI  - Reply to "Comment on 'In Vivo Drug Delivery Performance of Lipiodol-Based
      Emulsion or Drug-Eluting Beads in Patients with Hepatocellular Carcinoma'".

PMID- 29185768
TI  - Focused Genome Mining of Structurally Related Sesterterpenes: Enzymatic Formation
      of Enantiomeric and Diastereomeric Products.
AB  - Heterologous expression of four clade-A bifunctional terpene synthases (BFTSs),
      giving di/sesterterpenes with unique polycyclic carbon skeletons such as
      sesterfisherol, enabled the isolation of the sesterterpenes Bm1, Bm2, Bm3, and
      Pb1. Their structures suggested that formation of the products occurs via various
      diastereomeric carbocation intermediates, allowing the proposal that clade-A
      BFTSs catalyze three-step cyclizations using several stereofacial combinations of
      allylic cation-olefin pairs in the corresponding intermediates to generate
      various stereoisomers.

PMID- 29185769
TI  - Drug Repurposing Approach Identifies a Synergistic Drug Combination of an
      Antifungal Agent and an Experimental Organometallic Drug for Melanoma Treatment.
AB  - By screening a drug library comprising FDA approved compounds, we discovered a
      potent interaction between the antifungal agent haloprogin and the experimental
      organometallic drug RAPTA-T, to synergistically induce cancer cell killing. The
      combination of these two small molecules, even at low doses, elicited an improved
      therapeutic response on tumor growth over either agent alone or the current
      treatment used in the clinic in the highly aggressive syngeneic B16F10 melanoma
      tumor model, where classical cytotoxic chemotherapeutic agents show little
      efficacy. The combination with the repurposed chemodrug haloprogin provides the
      basis for a new powerful treatment option for cutaneous melanoma. Importantly,
      because synergistic induction of tumor cell death is achieved with low individual
      drug doses, and cellular targets for RAPTA-T are different from those of
      classical chemotherapeutic drugs, a therapeutic strategy based on this approach
      could avoid toxicities and potentially resistance mechanisms, and could even
      inhibit metastatic progression.

PMID- 29185770
TI  - Producing Atomically Abrupt Axial Heterojunctions in Silicon-Germanium Nanowires
      by Thermal Oxidation.
AB  - Compositional abruptness of the interfaces is one of the important factors to
      determine the performance of Group IV semiconductor heterojunction (Si/Ge or
      Si/SiGe) nanowire devices. However, forming abrupt interfaces in the nanowires
      using the common vapor-liquid-solid (VLS) method is restricted because large
      solubility of Si and Ge in the Au eutectic liquid catalyst makes gradual
      composition change at the heterojunction after switching the gas phase
      components. According to the VLS growth mechanism, another possible approach to
      form an abrupt interface is making a change of the semiconductor concentration in
      the eutectic liquid before precipitation of the second phase. Here we show that
      the composition in AuSiGe eutectic liquid on SiGe nanowires of low Ge
      concentration (<=6%) can be altered by thermal oxidation at 700  degrees C.
      During the oxidation process, only Si is oxidized on the surface of the eutectic
      liquid, and the Ge/Si ratio in the eutectic liquid is increased. The subsequently
      precipitated SiGe step at the liquid/solid interface has a higher Ge
      concentration (~20%), and a compositionally abrupt interface is produced in the
      nanowires. The growth mechanism of the heterojunction includes diffusion of Si
      and Ge atoms on nanowire surface into the AuSiGe eutectic liquid and step
      nucleation at the liquid/nanowire interface.

PMID- 29185771
TI  - Centimeter-Long Single-Crystalline Si Nanowires.
AB  - The elongation of free-standing one-dimensional (1D) functional nanostructures
      into lengths above the millimeter range has brought new practical applications as
      they combine the remarkable properties of nanostructured materials with
      macroscopic lengths. However, it remains a big challenge to prepare 1D silicon
      nanostructures, one of the most important 1D nanostructures, with lengths above
      the millimeter range. Here we report the unprecedented preparation of ultralong
      single-crystalline Si nanowires with length up to 2 cm, which can function as the
      smallest active material to facilitate the miniaturization of macroscopic
      devices. These ultralong Si nanowires with augmented flexibility are of emerging
      interest for flexible electronics. We also demonstrate the first single-nanowire
      based wearable joint motion sensor with superior performance to reported systems,
      which just represents one example of novel devices that can be built from these
      nanowires. The preparation of ultralong Si nanowires will stimulate the
      fabrication and miniaturization of electric, optical, medical, and mechanical
      devices to impact the semiconductor industry and our daily life in the near
      future.

PMID- 29185772
TI  - Six Stages of Microdroplet Detachment from Microscale Fibers.
AB  - The detachment of droplets from cylindrical fibers is of fundamental importance
      for both scientific research and engineering applications. Due to the challenges
      to determine dynamic contact angles on the fiber surface, the process of the
      droplet detachment from a fiber is not well understood. In this paper, a
      multibody dissipative particle dynamics (MDPD) method, a particle-based mesh-free
      method that can automatically capture the dynamic contact angles through direct
      modeling of liquid-solid particle interactions, was applied to study the
      detachment process of a liquid microdroplet from a cylindrical solid fiber pulled
      by an atomic force microscopy (AFM) tip under a constant velocity. After the
      validation of the numerical results through comparison with experiments in a
      benchmark case, the same numerical tool was applied to analyze the droplet
      detachment mechanisms. Based on the slope of the time history curve for the
      displacement of the droplet mass center, the detachment process can be divided
      into six stages. The change of slope in each stage can be explained from the
      change of surface energy. The results can greatly advance the fundamental
      understanding of the detachment process of microdroplets from cylindrical fibers.

PMID- 29185773
TI  - Ruthenium-Catalyzed C-H Activation of Salicylaldehyde and Decarboxylative
      Coupling of Alkynoic Acids for the Selective Synthesis of Homoisoflavonoids and
      Flavones.
AB  - Homoisoflavonoids were formed in DMSO exclusively, and flavones were formed in t
      AmOH when salicylaldehyde and alkynoic acids reacted with [Ru(p-cymene)Cl2]2 and
      CsOAc. They were formed through C-H activation of salicylaldehyde and
      decarboxylative coupling of alkynoic acid. This reaction system showed good
      yields, broad substrate scope, and good functional group tolerance. It was found
      that chalcone was an intermediate in the formation of both homoisoflavonoid and
      flavone.

PMID- 29185774
TI  - Silver-Catalyzed Cyclopropanation of Alkenes Using N-Nosylhydrazones as Diazo
      Surrogates.
AB  - An efficient silver-catalyzed [2 + 1] cyclopropanation of sterically hindered
      internal alkenes with diazo compounds in which room-temperature-decomposable N
      nosylhydrazones are used as diazo surrogates is reported. The unexpected unique
      catalytic activity of silver was ascribed to its dual role as a Lewis acid
      activating alkene substrates and as a transition metal forming silver carbenoids.
      A wide range of internal alkenes, including challenging diarylethenes, were
      suitable for this protocol, thereby affording a variety of cyclopropanes with
      high efficiency in a stereoselective manner under mild conditions.

PMID- 29185775
TI  - Molecular Oxygen-Mediated Minisci-Type Radical Alkylation of Heteroarenes with
      Boronic Acids.
AB  - The carbon-carbon bond formation via autoxidation of organoboronic acid using 1
      atm of O2 is achieved in a simple, clean, and green fashion. The approach allows
      a technically facile and environmentally benign access to structurally diverse
      heteroaromatics with medicinally privileged scaffolds. The strategy also displays
      its practicality and sustainability in the resynthesis of marketed drugs Crestor
      and pyrimethamine.

PMID- 29185776
TI  - Direct Room Temperature Welding and Chemical Protection of Silver Nanowire Thin
      Films for High Performance Transparent Conductors.
AB  - Silver nanowire (Ag-NW) thin films have emerged as a promising next-generation
      transparent electrode. However, the current Ag-NW thin films are often plagued by
      high NW-NW contact resistance and poor long-term stability, which can be largely
      attributed to the ill-defined polyvinylpyrrolidone (PVP) surface ligands and
      nonideal Ag-PVP-Ag contact at NW-NW junctions. Herein, we report a room
      temperature direct welding and chemical protection strategy to greatly improve
      the conductivity and stability of the Ag-NW thin films. Specifically, we use a
      sodium borohydride (NaBH4) treatment process to thoroughly remove the PVP ligands
      and produce a clean Ag-Ag interface that allows direct welding of NW-NW junctions
      at room temperature, thus greatly improving the conductivity of the Ag-NW films,
      outperforming those obtained by thermal or plasmonic thermal treatment. We
      further show that, by decorating the as-formed Ag-NW thin film with a dense,
      hydrophobic dodecanethiol layer, the stability of the Ag-NW film can be greatly
      improved by 150-times compared with that of PVP-wrapped ones. Our studies
      demonstrate that a proper surface ligand design can effectively improve the
      conductivity and stability of Ag-NW thin films, marking an important step toward
      their applications in electronic and optoelectronic devices.

PMID- 29185777
TI  - Systematic Testing of Belief-Propagation Estimates for Absolute Free Energies in
      Atomistic Peptides and Proteins.
AB  - Motivated by the extremely high computing costs associated with estimates of free
      energies for biological systems using molecular simulations, we further the
      exploration of existing "belief propagation" (BP) algorithms for fixed-backbone
      peptide and protein systems. The precalculation of pairwise interactions among
      discretized libraries of side-chain conformations, along with representation of
      protein side chains as nodes in a graphical model, enables direct application of
      the BP approach, which requires only ~1 s of single-processor run time after the
      precalculation stage. We use a "loopy BP" algorithm, which can be seen as an
      approximate generalization of the transfer-matrix approach to highly connected
      (i.e., loopy) graphs, and it has previously been applied to protein calculations.
      We examine the application of loopy BP to several peptides as well as the binding
      site of the T4 lysozyme L99A mutant. The present study reports on (i) the
      comparison of the approximate BP results with estimates from unbiased estimators
      based on the Amber99SB force field; (ii) investigation of the effects of varying
      library size on BP predictions; and (iii) a theoretical discussion of the
      discretization effects that can arise in BP calculations. The data suggest that,
      despite their approximate nature, BP free-energy estimates are highly accurate
      indeed, they never fall outside confidence intervals from unbiased estimators for
      the systems where independent results could be obtained. Furthermore, we find
      that libraries of sufficiently fine discretization (which diminish library-size
      sensitivity) can be obtained with standard computing resources in most cases.
      Altogether, the extremely low computing times and accurate results suggest the BP
      approach warrants further study.

PMID- 29185778
TI  - Extent of Surface Force Additivity on Chemically Heterogeneous Substrates at
      Varied Orientations.
AB  - Surface interactions between chemically mixed surfaces, as well as those among
      dissolved biomolecules, comprise distinct contributions from polar and
      hydrophobic moieties. These contributions are often context dependent.
      Approximate compliance to the Cassie additivity equation for the wetting free
      energies on mixed surfaces in water is, however, indicative of similarly additive
      forces between individual surface elements, suggesting a quadratic interpolation
      model for total force from the forces between pure surfaces. We use molecular
      dynamics/umbrella sampling simulations of parallel and nonparallel mixed surfaces
      with demonstrable Cassie-like behavior to verify how well the total surface force
      between the heterogeneous, molecularly rough surfaces can be approximated as a
      combination of forces among the homogeneous ones. When accounting for dissimilar
      distances of approach between functional groups of different types, our results
      for graphene surfaces with mixed methyl and nitrile coating show such a
      superposition to provide a reasonable first order approximation of interactions
      between the platelets. Deviations from additivity are more prominent in parallel
      plate configurations, at high content of hydrophobic groups, and small
      separations. The inclusion of water polarizability does not visibly alter the
      observed behavior regardless of platelet orientations. The outcome of this study
      determines the necessary molecular conditions for observing force additivity that
      emphasize the context dependence of hydrophobic interaction in the presence of
      polar groups. This notion provides guidelines for the syntheses of new,
      chemically heterogeneous materials with tailored function-oriented properties in
      aqueous media.

PMID- 29185780
TI  - Effects of Saffron on Cognition, Anxiety, and Depression in Patients Undergoing
      Coronary Artery Bypass Grafting: A Randomized Double-Blind Placebo-Controlled
      Trial.
AB  - OBJECTIVES: Cognitive decline, depression, and anxiety are among the major
      concerns in patients undergoing coronary artery bypass grafting (CABG). Crocus
      sativus L. (saffron) seems to be a promising candidate for treatment of these
      conditions. DESIGN: In this 12-week, randomized, double-blind, placebo-controlled
      clinical trial, men and women with on-pump CABG, who had Wechsler Memory Scale
      (WMS) score >70 and age <70 years, received either saffron capsules (15 mg/twice
      daily) or placebo. Patients were excluded if they had history of treatment with
      saffron or acetylcholinesterase inhibitors, comorbid neuropsychiatric disorders,
      serious medical conditions other than cardiovascular diseases, and
      hypersensitivity to herbal compounds. The primary outcome was defined as the
      difference in mean total score changes for WMS-Revised from the baseline to week
      12 between the saffron and placebo groups. Secondary outcomes included difference
      in mean score changes from baseline to endpoint between the two treatment groups
      for Mini Mental Status Examination and subscales of Hospital Anxiety and
      Depression Scale ( www.irct.ir ; IRCT201408071556N63). RESULTS: No significant
      difference was detected in primary or secondary outcomes between the saffron and
      placebo groups. Also, no significant time * treatment interaction effect was
      found for any of the scales. CONCLUSIONS: The results of this trial do not
      support the hypothesis of potential benefits of saffron in treatment of CABG
      related neuropsychiatric conditions.

PMID- 29185779
TI  - Quasi-Two-Dimensional Phase Transition of Methane Adsorbed in Cylindrical Silica
      Mesopores.
AB  - Using Monte Carlo and molecular dynamics simulations, we examine the adsorption
      of methane in cylindrical silica mesopores in an effort to understand a possible
      phase transition of adsorbed methane in MCM-41 and SBA-15 silica that was
      previously identified by an unexpected increase in the adsorbed fluid density
      following capillary condensation, as measured by small-angle neutron scattering
      (SANS) [Chiang, W-S., et al., Langmuir 2016, 32, 8849]. Our initial simulation
      results identify a roughly 10 % increase in the density of the liquidlike
      adsorbed phase for either an isotherm with increasing pressure or an isobar with
      decreasing temperature and that this densification is associated with a local
      maximum in the isosteric enthalpy of adsorption. Subsequent analysis of the
      simulated fluid, via computation of bond-orientational order parameters of
      specific annular layers of the adsorbed fluid, showed that the layers undergo an
      ordering transition from a disordered, amorphous state to one with two
      dimensional hexagonal structure. Furthermore, this two-dimensional restructuring
      of the fluid occurs at the same thermodynamic state points as the aforementioned
      densification and local maximum in the isosteric enthalpy of adsorption. We thus
      conclude that the densification of the fluid is the result of structural
      reorganization, which is signaled by the maximum in the isosteric enthalpy. Owing
      to the qualitative similarity of the structural transitions in the simulated and
      experimental methane fluids, we propose this hexagonal reorganization as a
      plausible explanation of the densification observed in SANS measurements. Lastly,
      we speculate how this structural transition may impact the transport properties
      of the adsorbed fluid.

PMID- 29185781
TI  - Osteochondral Allograft Transplantation of the Knee in Patients Aged 40 Years and
      Older.
AB  - BACKGROUND: Treatment of large chondral defects of the knee among patients aged
      >=40 years remains a difficult clinical challenge owing to preexisting joint
      degeneration and the lack of treatment options short of arthroplasty. PURPOSE: To
      characterize the survivorship, predictors of failure, and clinical outcomes of
      osteochondral allograft transplantation (OCA) of the knee among patients aged
      >=40 years. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Prospectively collected data were reviewed for 54 consecutive patients aged >=40
      years who were treated with OCA. Preoperative levels of osteoarthritis (according
      to Kellgren-Lawrence classification) and meniscal volume and quality were graded
      from review of radiographs and magnetic resonance imaging. Complications,
      reoperations, and patient responses to validated outcome measures were reviewed.
      A minimum follow-up of 2 years was required for analysis. Failure was defined by
      any removal or revision of the allograft or conversion to arthroplasty. RESULTS:
      Among 51 patients (mean age, 48 years; range, 40-63 years; 65% male), a total of
      52 knees had symptomatic focal cartilage lesions (up to 2 affected areas) that
      were classified as Outerbridge grade 4 at the time of OCA and did not involve
      substantial bone loss requiring shell allografts or additional bone grafting.
      Mean duration of follow-up was 3.6 years (range, 2-11 years). After OCA, 21 knees
      (40%) underwent reoperation, including 14 failures (27%) consisting of revision
      OCA (n = 1), unicompartmental knee arthroplasty (n = 5), and total knee
      arthroplasty (n = 8). Mean time to failure was 33 months, and 2- and 4-year
      survivorship rates were 88% and 73%, respectively. Male sex (hazard ratio = 4.18,
      95% CI = 1.12-27.13) and a higher number of previous ipsilateral knee operations
      (hazard ratio = 1.70 per increase in 1 surgical procedure, 95% CI = 1.03-2.83)
      were predictors of failure. A higher Kellgren-Lawrence osteoarthritis grade on
      preoperative radiographs was associated with higher failure rates in the Kaplan
      Meier analysis but not the multivariate model. At final follow-up, clinically
      significant improvements were noted in the pain (mean score, 47.8 to 67.6) and
      physical functioning (56.8 to 79.1) subscales of the Short Form-36, as well as
      the International Knee Documentation Committee subjective form (45.0 to 63.6),
      Knee Outcome Survey-Activities of Daily Living (64.5 to 80.1), and overall
      condition statement (4.5 to 6.8) ( P < .001). No significant changes were noted
      for the Marx Activity Rating Scale (5.1 to 3.9, P = .789). CONCLUSION: A higher
      failure rate was found in this series of patients aged >=40 years who were
      treated with OCA as compared with other studies of younger populations. However,
      for select older patients, OCA can be a good midterm treatment option for
      cartilage defects of the knee.

PMID- 29185783
TI  - Comparison of recidivism rates for a teenage trauma prevention program after the
      addition of high-fidelity patient simulation.
AB  - OBJECTIVES: We evaluated the benefits of adding high-fidelity simulation to a
      teenage trauma prevention program to decrease recidivism rates and encourage
      teens to discuss actionable steps toward safe driving. METHODS: A simulated
      pediatric trauma scenario was integrated into an established trauma prevention
      program. Participants were recruited because they were court-ordered to attend
      this program after misdemeanor convictions for moving violations. The teenage
      participants viewed this simulation from the emergency medical services (EMS)
      handoff to complete trauma care. Participants completed a postsimulation
      knowledge assessment and care evaluation, which included narrative data about the
      experience. Qualitative analysis of color-coded responses identified common
      themes and experiences in participants' answers. Court records were reviewed 6
      years after course completion to determine short- and long-term recidivism rates,
      which were then compared to our program's historical rate. RESULTS: One hundred
      twenty-four students aged 16-20 years participated over a 2-year study period.
      Narrative responses included general reflection, impressions, and thoughts about
      what they might change as a result of the course. Participants reported that they
      would decrease speed (30%), wear seat belts (15%), decrease cell phone use (11%),
      and increase caution (28%). The recidivism rate was 55% within 6 years. At 6
      months it was 8.4%, at 1 year it was 20%, and it increased approximately 5-8% per
      year after the first year. Compared with our programs, for historical 6-month and
      2-year recidivism rates, no significant difference was seen with or without
      simulation. CONCLUSIONS: Adding simulation is well received by participants and
      leads to positive reflections regarding changes in risk-taking behaviors but
      resulted in no changes to the high recidivism rates This may be due to the often
      ineffectiveness of fear appeals.

PMID- 29185782
TI  - Reemergence of Blended Tube Feeding and Parent's Reported Experiences in Their
      Tube Fed Children.
AB  - OBJECTIVE: Healthcare providers (HCPs) report increased interest in blenderized
      tube feeding (BTF) as an alternative to commercial formula (CF) feeding
      particularly in families of tube fed children. The objective of this study was to
      explore parents' reported experiences of CF and BTF in their children. DESIGN:
      Prospective descriptive study utilizing a convenience sample. SETTING/SUBJECTS:
      Parents (n = 433) of tube fed children in an online tube feeding support group
      completed an electronic survey to compare experiences of CF and BTF in their tube
      fed children. RESULTS: The sample was evenly represented by parents using CF
      (50.5%) and BTF (49.5%). Reasons parents chose BTF included desire to provide
      whole foods (20.2%), decrease symptoms of tube feeding intolerance (19.7%),
      provide family meals (12.2%), increase oral intake (10.8%), address allergies
      (5.3%), or because they did not like formula (19.7%). Parents reported fewer
      symptoms of tube feeding intolerance on BTF and their children more frequently
      met growth goals compared to formula feeding. Only half (49.3%) of parents using
      BTF referred to HCPs for recipes and feeding oversight. The primary reasons
      parents did not use BTF included lack of knowledge (50.9%) or time constraints
      (20.0%). CONCLUSIONS: A significant number of parents in this sample successfully
      provide full or partial BTF to their children but only half rely on HCPs for
      guidance. There is wide variability in BTF preparation and delivery. Parents who
      use or have interest in BTF need knowledgeable and supportive HCPs for guidance
      and follow-up due to the unique nutritional needs of this patient population.
      HCPs need to be prepared to screen families of tube fed children who are using
      BTF or are interested in this feeding alternative to CF. Healthcare facilities
      need to evaluate their enteral feeding policies to accommodate patients on BTF.

PMID- 29185784
TI  - miR-21 Inhibitors Modulate Biological Functions of Gastric Cancer Cells via
      PTEN/PI3K/mTOR Pathway.
AB  - Gastric cancer is one of the most common malignancy in the world. microRNAs
      (miRNAs) are naturally occurring noncoding RNA that control gene expression by
      targeting messenger RNA (mRNA) for post-transcriptional repression or cleavage.
      This study focused on a specific miRNA, miR-21, which was overexpressed in
      gastric cancer and examined the effects of miR-21 inhibitor on biological
      functions of gastric cancer cells and its possible mechanism. Gastric cancer
      cells MKN74 were treated with miR-21 inhibitor, negative control, and blank
      control. Cell proliferation, colony formation, migration, and invasion were
      assessed. Real-time PCR and western blot were applied to examine the expression
      of phosphatase and tens in homolog deleted on chromosome ten (PTEN)/PI3K/mTOR
      pathway molecules. miR-21 inhibitor markedly suppressed proliferation, migration,
      invasion, and colony formation of gastric cancer cells. Anti-miR-21 treatment
      also reduced the expression ratio of B cell lymphoma 2 (Bcl-2)/Bax. Furthermore,
      miR-21 inhibition was associated with increased expression of PTEN, which in turn
      decreased the ratios of S235/236, S240/244, and p-AK/AKT in gastric cancer cells.
      Inhibiting miR-21 modulates biological functions of gastric cancer cells via
      PTEN/PI3K/mTOR pathway and miR-21 inhibitor may provide a novel therapeutic
      strategy for gastric cancer.

PMID- 29185785
TI  - Functional outcomes of motor vehicle crash thoracic injuries in pediatric and
      adult occupants.
AB  - OBJECTIVE: Characterization of the severity of injury should account for both
      mortality and disability. The objective of this study was to develop a disability
      metric for thoracic injuries in motor vehicle crashes (MVCs) and compare the
      functional outcomes between the pediatric and adult populations. METHODS:
      Disability risk (DR) was quantified using Functional Independence Measure (FIM)
      scores within the National Trauma Data Bank for the most frequently occurring
      Abbreviated Injury Scale (AIS) 2-5 thoracic injuries. Occupants with thoracic
      injury were classified as disabled or not disabled based on the FIM scale, and
      comparisons were made between the following age groups: pediatric, adult, middle
      aged, and older occupants (ages 7-18, 19-45, 46-65, and 66+, respectively). For
      each age group, DR was calculated by dividing the number of patients who were
      disabled and sustained a given injury by the number of patients who sustained a
      given injury. To account for the effect of higher severity co-injuries, a maximum
      AIS adjusted DR (DRMAIS) was also calculated for each injury. DR and DRMAIS could
      range from 0 to 100% disability risk. RESULTS: The mean DRMAIS for MVC thoracic
      injuries was 20% for pediatric occupants, 22% for adults, 29% for middle-aged
      adults, and 43% for older adults. Older adults possessed higher DRMAIS values for
      diaphragm laceration/rupture, heart laceration, hemo/pneumothorax, lung
      contusion/laceration, and rib and sternum fracture compared to the other age
      groups. The pediatric population possessed a higher DRMAIS value for flail chest
      compared to the other age groups. CONCLUSION: Older adults had significantly
      greater overall disability than each of the other age groups for thoracic
      injuries. The developed disability metrics are important in quantifying the
      significant burden of injuries and loss of quality life years. Such metrics can
      be used to better characterize severity of injury and further the understanding
      of age-related differences in injury outcomes, which can influence future age
      specific modifications to AIS.

PMID- 29185786
TI  - Desvenlafaxine Versus Placebo in the Treatment of Children and Adolescents with
      Major Depressive Disorder.
AB  - OBJECTIVE: To evaluate the short-term efficacy and safety of desvenlafaxine
      versus placebo in the treatment of children and adolescents with major depressive
      disorder (MDD). METHODS: Outpatient children (7-11 years) and adolescents (12-17
      years) who met DSM-IV-TR criteria for MDD and had screening and baseline
      Children's Depression Rating Scale-Revised (CDRS-R) total scores >40 were
      randomly assigned to 8 weeks of treatment with placebo, low exposure
      desvenlafaxine (20, 30, or 35 mg/day based on baseline weight), or higher
      exposure desvenlafaxine (25, 35, or 50 mg/day based on baseline weight). The
      primary efficacy endpoint was change from baseline in CDRS-R total score at week
      8, analyzed using a mixed-effects model for repeated measures. Secondary efficacy
      assessments included Clinical Global Impressions-Severity and Clinical Global
      Impressions-Improvement scales. Safety assessments included adverse events and
      the Columbia-Suicide Severity Rating Scale. RESULTS: The safety population
      included 363 patients (children, n = 109; adolescents, n = 254). No statistical
      separation from placebo was observed for either desvenlafaxine group for CDRS-R
      total score or for any secondary efficacy endpoint. At week 8, adjusted mean
      (standard error) changes from baseline in CDRS-R total score for the
      desvenlafaxine low exposure, desvenlafaxine high exposure, and placebo groups
      were -23.7 (1.1), -24.4 (1.1), and -22.9 (1.1), respectively. The incidence of
      adverse events was similar among groups. CONCLUSION: Low and high exposure
      desvenlafaxine groups did not demonstrate efficacy for the treatment of MDD in
      children and adolescents in this double-blind, placebo-controlled trial.
      Desvenlafaxine (20-50 mg/day) was generally safe and well tolerated with no new
      safety signals identified in pediatric patients with MDD in this study.

PMID- 29185787
TI  - Impact of Game-Based Health Promotion Programs on Body Mass Index in
      Overweight/Obese Children and Adolescents: A Systematic Review and Meta-Analysis
      of Randomized Controlled Trials.
AB  - BACKGROUND: Sedentary lifestyle is growing among children and adolescents that
      may contribute to problems such as overweight and obesity. Consequently,
      interventions to improve weight loss in this population are necessary. The aim of
      this current review was to evaluate the effectiveness of game-based interventions
      to reduce body mass index (BMI) among children who were overweight or obese.
      METHODS: All randomized controlled trials with a game-based approach for lowering
      weight in obese/overweight youths aged 5-18 years old were identified from
      January 2005 to June 2017 across PubMed, Web of Science, Embase, Scopus, and
      ScienceDirect. Two independent reviewers completed data extraction sheets on
      information such as sample size, country of origin, age of participants, type of
      interventions, and BMI change from pre- to posttest. A consensus on collected
      data was obtained, and a final list of studies meeting inclusion and exclusion
      criteria was arrived at. Data were analyzed using Comprehensive Meta-analysis
      software, and effect size was measured by standardized mean difference (SMD) and
      Hedges' g measure. Heterogeneity and publication bias were also examined using I2
      index and funnel plot. RESULTS: A total of 388 articles were identified from
      electronic and manuals' searches. After deletion of duplicated articles, 138
      articles remained that were then screened in terms of relevance. Of those, 41
      articles were examined to determine eligibility. Finally, 10 articles met
      inclusion/exclusion criteria and were entered into the quantitative meta
      analysis. Results indicated a small but significant effect size in terms of BMI
      reduction [SMD, -0.234; standard error (SE), 0.069] among included studies. The
      average BMI z-score reduction was -0.181 (SE, 0.071). Trials which used other
      types of interventions along with active game-based approaches achieved greater
      effect sizes than single game-based interventions. There was a significant
      difference between studies based on their country of origin, BMI value, and
      intervention type. Those conducted in United States, those including participants
      with BMI >=30, and studies with multicomponent intervention reported a higher
      reduction of BMI than others. However, no significant difference in BMI was found
      in terms of variables such as age, sample size, type of participant
      (overweight/obese), intervention duration, or participant gender. No publication
      bias was identified, and studies were homogenous (I2 = 22.5%). CONCLUSIONS:
      Interventions that involve active gaming may produce small effects in terms of
      improving BMI among children who are overweight/obese. Therefore, we recommend
      that supplemental interventions be used to enhance the effectiveness of game
      based interventions.

PMID- 29185788
TI  - Risk factors for motorcycle loss-of-control crashes.
AB  - OBJECTIVE: The present article identifies and assesses the effect of critical
      factors on the risk of motorcycle loss-of-control (LOC) crashes. METHOD: Data
      come from a French project on road crashes, which include all fatal road crashes
      and a random sample of 1/20th of nonfatal crashes in France in 2011, based on
      police reports. A case-control study was carried out on a sample of 903 crashes
      for 444 LOC motorcycle riders (case) and 470 non-LOC and nonresponsible
      motorcycle riders (control). The sample was weighted due to the randomization of
      nonfatal crashes. Missing values were imputed using multiple imputation. RESULTS:
      Road alignment and surface conditions, human factors, and motorcycle type played
      important roles in motorcycle LOC crashes. Riding in a curve was associated with
      a 3-fold greater risk of losing control of motorcycle than riding in a straight
      line. Poor road adhesion significantly increased the risk of losing control; the
      risk increased more than 20-fold when deteriorated road adhesion was encountered
      unexpectedly, due to loose gravel, ice, oil, bumps, road marking, metal plates,
      etc. For motorcyclists, riding with a positive blood alcohol concentration (over
      or equal to the legal limit of 0.5 g/L) was very dangerous, often resulting in
      losing control. The risk of LOC crash varied for different types of motorcycle:
      Riders of roadsters and sports bikes were more likely to have an LOC crash
      greater than that of riders of basic or touring motorcycles. In addition, LOC
      risk increased with speed; a model using the square of the traveling speed showed
      better fit than one using speed itself. CONCLUSION: The LOC crash factors related
      to riders, vehicles, and road infrastructure identified here were expected but
      were rarely identified and taken simultaneously into account in previous studies.
      They could be targeted by countermeasures to improve motorcyclist safety.

PMID- 29185789
TI  - Integrated Treatment of Prostaglandin E1 and Angiotensin-Converting Enzyme
      Inhibitor in Diabetic Kidney Disease Rats: Possible Role of Antiapoptosis in
      Renal Tubular Epithelial Cells.
AB  - To investigate the therapeutic mechanisms underlying prostaglandin E1 (PGE1) and
      angiotensin-converting enzyme inhibitor (ACEI) on reducing urinary protein in
      diabetic kidney disease (DKD). DKD rats were established and randomly divided
      into four groups: PGE1 (10 MUg/kg/day) (P group), ACEI (10 mg/kg/day) (A group),
      combination of PGE1 with ACEI treatment (P + A group), and saline treatment group
      (DKD group). Untreated rats were used as normal control (N group). Urinary
      albumin, endothelin-1 (ET-1), angiotensin II (AngII), TUNEL assay, Masson's
      trichrome staining, and immunohistochemistry staining for CD68 were evaluated in
      all groups. Ten days after treatment, urinary albumin was significantly decreased
      in the P and P + A groups (p < 0.01 vs. the DKD group). At the end of 8 weeks,
      the albumin was still significantly reduced in the P + A group (p < 0.05 vs. the
      A group). ET-1 and AngII were also significantly decreased in three treatment
      groups (p < 0.01 vs. the DKD group), especially in the P + A group. Few cells
      underwent apoptosis in glomerular regions in DKD rats, while amounts of apoptotic
      cells were seen in tubules regions. Further, apoptosis and the areas of fibrosis
      in tubulointerstitial were both decreased most in the P + A group compared with
      the DKD group. Apoptosis of renal tubular epithelial cells may participate in the
      development and progression of DKD in rats. Combination of PGE1 with AGEI
      remarkably protects renal function compared with PGE1 or ACEI monotherapy. The
      potential therapeutic mechanisms of PGE1 and AGEI might be via multiple targets
      and, at least in part, through inhibiting the apoptosis of renal tubular
      epithelial cells.

PMID- 29185790
TI  - Sox9 Functions as a Master Regulator of Antler Growth by Controlling Multiple
      Cell Lineages.
AB  - Deer antlers are amazing natural appendages that grow faster than any other known
      mammalian bone. Antler growth occurs at the tip and is initially cartilage, which
      is later replaced by bone tissue. However, little is known regarding the precise
      role of cooperation between cell lineages and functional genes in regulating
      antler growth, and molecular mechanisms responsible for rapid growth remain
      elusive. In this study, we use an RNA-Seq approach to elucidate the full spectrum
      of cell lineages, functional genes, and their cooperative interactions during
      antler growth. We identify Sox9 as a pivotal transcription factor during
      chondrogenesis and skeletal development expressed in the chondrocyte lineage from
      the multipotent mesenchymal precursor stage through most subsequent cell
      differentiation stages with a particularly strong activity in proliferating and
      prehypertrophic chondrocytes. Furthermore, we analyze the miRNA expression
      patterns at initial growth stage and rapid growth stage and identify several
      miRNAs that involve in regulating antler chondrogenesis and rapid growth. Among
      these miRNAs, miR-140 plays pivotal role during antler growth by targeting Sox9
      and vice versa.

PMID- 29185791
TI  - Recovery of Anthocyanins Using Membrane Technologies: A Review.
AB  - Anthocyanins are naturally occurring polyphenolic compounds and give many
      flowers, fruits and vegetable their orange, red, purple and blue colors. Besides
      their color attributes, anthocyanins have received much attention in recent years
      due to the growing evidence of their antioxidant capacity and health benefits on
      humans. However, these compounds usually occur in low concentrations in mixtures
      of complex matrices, and therefore large-scale harvesting is needed to obtain
      sufficient amounts for their practical usage. Effective fractionation or
      separation technologies are therefore essential for the screening and production
      of these bioactive compounds. In this context, membrane technologies have become
      popular due to their operational simplicity, the capacity to achieve good
      simultaneous separation/pre-concentration and matrix reduction with lower
      temperature and lower operating cost in comparison to other sample preparation
      methods. Membrane fractionation is based on the molecular or particle sizes
      (pressure-driven processes), on their charge (electrically driven processes) or
      are dependent on both size and charge. Other non-pressure-driven membrane
      processes (osmotic pressure and vapor pressure-driven) have been developed in
      recent years and employed as alternatives for the separation or fractionation of
      bioactive compounds at ambient conditions without product deterioration. These
      technologies are applied either individually or in combination as an integrated
      membrane system to meet the different requirements for the separation of
      bioactive compounds. The first section of this review examines the basic
      principles of membrane processes, including the different types of membranes,
      their structure, morphology and geometry. The most frequently used techniques are
      also discussed. Last, the specific application of these technologies for the
      separation, purification and concentration of phenolic compounds, with special
      emphasis on anthocyanins, are also provided.

PMID- 29185792
TI  - MetReS, an Efficient Database for Genomic Applications.
AB  - MetReS (Metabolic Reconstruction Server) is a genomic database that is shared
      between two software applications that address important biological problems.
      Biblio-MetReS is a data-mining tool that enables the reconstruction of molecular
      networks based on automated text-mining analysis of published scientific
      literature. Homol-MetReS allows functional (re)annotation of proteomes, to
      properly identify both the individual proteins involved in the processes of
      interest and their function. The main goal of this work was to identify the areas
      where the performance of the MetReS database performance could be improved and to
      test whether this improvement would scale to larger datasets and more complex
      types of analysis. The study was started with a relational database, MySQL, which
      is the current database server used by the applications. We also tested the
      performance of an alternative data-handling framework, Apache Hadoop. Hadoop is
      currently used for large-scale data processing. We found that this data handling
      framework is likely to greatly improve the efficiency of the MetReS applications
      as the dataset and the processing needs increase by several orders of magnitude,
      as expected to happen in the near future.

PMID- 29185793
TI  - Viability Assessment of Cryptosporidium parvum Oocysts by Vital Dyes: Dry Mounts
      Overestimate the Number of "Ghost" Oocysts.
AB  - Viability assessment of Cryptosporidium parvum oocysts is crucial for evaluation
      of the public health significance of this important zoonotic protozoon. Viability
      is commonly assessed in wet mounts after acid pretreatment and staining with
      fluorogenic vital dyes. However, in some studies, oocyst viability is evaluated
      in dry mounts after staining in suspension. Here, we evaluate the effect of acid
      pretreatment in nine replicate samples and compare the assessment of oocyst
      viability after evaluation in wet and dry mounts, respectively. Although acid
      pretreatment had no significant effect on the viability scores, data obtained by
      scoring oocysts in dry mounts resulted in ~25% underestimation of the proportion
      of viable oocyst (82.5% +/- 0.9% [wet mount +acid], 57.7% +/- 2.3% [dry mount, /
      acid], 76.0% +/- 1.7% [wet mount, / acid]), while the proportions of nonviable
      oocysts (DAPI+/PI+) were comparable for wet and dry mounts (9.7% +/- 0.4% [wet
      mount +acid], 12.1 +/- 1.5% [dry mount, / acid], 15.5% +/- 1.1% [wet mount, /
      acid]).

PMID- 29185794
TI  - The effect of correct cross-chest clip use on injury outcomes in young children
      during motor vehicle crashes.
AB  - OBJECTIVE: Traffic crashes have high mortality and morbidity for young children.
      Though many specialized child restraint systems improve injury outcomes, no large
      scale studies have investigated the cross-chest clip's role during a crash,
      despite concerns in some jurisdictions about the potential for neck contact
      injuries from the clips. This study aimed to investigate the relationship between
      cross-chest clip use and injury outcomes in children between 0 and 4 years of
      age. METHODS: Child passengers between 0 and 4 years of age were selected from
      the NASS-CDS data sets (2003-2014). Multiple regression analysis was used to
      model injury outcomes while controlling for age, crash severity, crash direction,
      and restraint type. The primary outcomes were overall Abbreviated Injury Score
      (AIS) 2+ injury, and the presence of any neck injury. RESULTS: Across all
      children aged 0-4 years, correct chest clip use was associated with decreased
      Abbreviated Injury Scale (AIS) 2+ injury (odds ratio [OR] = 0.44, 95% confidence
      interval [CI], 0.21-0.91) and was not associated with neck injury. However,
      outcomes varied by age. In children <12 months old, chest clip use was associated
      with decreased AIS 2+ injury (OR = 0.09, 95% CI, 0.02-0.44). Neck injury (n = 7,
      all AIS 1) for this age group only occurred with correct cross-chest clip use.
      For 1- to 4-year-old children, cross-chest clip use had no association with AIS
      2+ injury, and correct use significantly decreased the odds of neck injury (OR =
      0.49; 95% CI, 0.27-0.87) compared to an incorrectly used or absent cross-chest
      clip. No serious injuries were directly caused by the chest clips. CONCLUSIONS:
      Correct cross-chest clip use appeared to reduce injury in crashes, and there was
      no evidence of serious clip-induced injury in children in 5-point harness
      restraints.

PMID- 29185795
TI  - Curcumin against advanced glycation end products (AGEs) and AGEs-induced
      detrimental agents.
AB  - OBJECTIVES: This study was aimed to review and collate effects of curcumin on
      generation of advanced glycation end products (AGEs) and AGEs induced detrimental
      agents. METHODS: Pubmed, Googlescholar, ScienceDirect, and Scopus databases were
      searched. Searching was not limited to specific publication period. Only English
      language original articles (in vitro, experimental and human) which had examined
      the effect of curcumin on AGEs formation and AGEs induced apoptosis, oxidative
      stress or inflammatory responses were included. To review effect of curcumin on
      AGEs formation, search terms were as following: ''curcumin" (title) and AGEs or
      pentosidine or methylglyoxal or carboxymethyllysine or glucosylation
      (title/abstract). Totally 104 articles were searched which 19 were selected for
      review. To review effect of curcumin on AGEs induced harmful agents, key words
      were as following: "curcumin" (title) and AGEs (title/abstract) and apoptosis or
      oxidative stress or DNA damage or cell injury or inflammatory or cell death or
      cell proliferation (title/abstract). Totally 126 articles were searched which 18
      were found appropriate for review. RESULTS: Regarding curcumin and AGEs
      formation, ten eligible articles (1 human trial, 5 animal models and 4 in vitro)
      and with regarding curcumin and AGEs-induced complications, 17 articles (5 on
      apoptosis, 9 on oxidative stress, and 3 on inflammatory responses) were selected.
      Except one, all studies indicated that curcumin is able to prevent AGEs formation
      and AGEs-induced disturbances with different potential mechanisms. CONCLUSION:
      Curcumin can inhibit AGEs formation and AGEs-induced disturbances. More RCT
      researches are suggested to evaluate beneficial effect of curcumin regarding AGEs
      in different age-related chronic diseases, with specific attention to AGEs
      memberships.

PMID- 29185796
TI  - Two-Dimensional Gas Chromatography Coupled With Mass Spectrometry in Food
      Analysis.
AB  - The development of instrumental analytical techniques provided the opportunity
      for in-depth characterization of many food matrices. In particular, the use of
      gas chromatography coupled with mass spectrometry gives impressive results in
      terms of quality and authenticity testing, conducting food freshness evaluations
      and contamination assessments. A new variant of gas chromatography, namely two
      dimensional gas chromatography (GC * GC), and various versions of mass
      spectrometry have been developed since last 15 years, and they still remain at
      the time of their renaissance. The present critical review is focused on the use
      of GC * GC coupled with mass spectrometry for qualitative and quantitative
      reasons in food analysis. It is explained how powerful analytical tool is above
      mentioned technical solution. Special attention is devoted to the issues related
      to the development of this technique during last years in terms of key
      construction elements, such as modulators and MS detectors. Finally, the critical
      discussion on many various aspects including advantages and more important
      disadvantages, caused probable moderate interest of this solution, in food
      analytics is concerned.

PMID- 29185797
TI  - U1 snDNA chromosomal mapping in ten spittlebug species (Cercopidade,
      Auchenorrhyncha, Hemiptera).
AB  - Spittlebugs, which belong to the family Cercopidae (Auchenorrhyncha, Hemiptera),
      form a large group of xylem-feeding insects that are best known for causing
      damage to plantations and pasture grasses. The holocentric chromosomes of these
      insects remain poorly studied in regards to the organization of different classes
      of repetitive DNA. To improve chromosomal maps based on repetitive DNAs and to
      better understand the chromosomal organization and evolutionary dynamics of
      multigene families in spittlebugs, we physically mapped the U1 snRNA gene with
      fluorescence in situ hybridization (FISH) in 10 species of Cercopidae belonging
      to three different genera. All the U1 snDNA clusters were autosomal and located
      in interstitial position. In seven species, they were restricted to one autosome
      per haploid genome, while three species of the genus Mahanarva showed two
      clusters in two different autosomes. Although it was not possible to precisely
      define the ancestral location of this gene, it was possible to observe the
      presence of at least one cluster located in a small bivalent in all karyotypes.
      The karyotype stability observed in Cercopidae is also observed in respect to the
      distribution of U1 snDNA. Our data are discussed in light of possible mechanisms
      for U1 snDNA conservation and compared with the available data from other
      species.

PMID- 29185798
TI  - Reproduction and monogamy in captive flock of greater flamingos (Phoenicopterus
      Roseus).
AB  - Due to the great number of greater flamingos in captivity and their long life
      span, studying their behavior and welfare might be useful to improve the
      husbandry and breeding of this species in zoos. This study aimed to investigate
      factors affecting the breeding activity of captive greater flamingos
      (Phoenicopterus roseus) from 2012 to 2016. To estimate reproductive success, the
      number of pairs, eggs laid, and hatchlings were recorded. In addition,
      information on age, egg-laying history of the partners, and pair composition was
      collected. An increase in the number of pairs, eggs, and hatchlings was reported
      over the years. For each breeding season, there were pairs who laid more than
      once, especially in 2014 and 2015. Approximately 50% of pairs were monogamous
      between consecutive years; however, the percentage dropped gradually when
      comparing nonconsecutive years. Senescence and previous experience seemed to
      affect the reproductive success of the study flamingos. In conclusion, different
      factors can influence the reproduction of greater flamingos in zoos. All these
      factors are related to nonhuman animal welfare and need to be considered in
      developing and improving management practices.

PMID- 29185799
TI  - Social inequality in phase II cardiac rehabilitation attendance: The impact of
      potential mediators.
AB  - BACKGROUND: Cardiac rehabilitation participation is an essential component of the
      contemporary management of coronary heart disease. However, patients with low
      socioeconomic position are less likely to attend the rehabilitation programme.
      AIM: We aimed to explore the effect of potential mediators between socioeconomic
      position defined by educational attainment and cardiac rehabilitation attendance.
      METHODS: Prospective observational study of patients with acute coronary syndrome
      ( N=302). Logistic regression and mediation analysis was conducted to explore
      mechanisms of non-attendance. RESULTS: Thirty per cent attended full cardiac
      rehabilitation. Patients with low educational attainment, comorbidities, long
      commute to cardiac rehabilitation centre, and lone dwelling were less likely to
      attend full cardiac rehabilitation, whereas patients with high anxiety and
      depression score were more likely to attend full cardiac rehabilitation. Patients
      with low educational attainment had lower self-efficacy and longer commute
      compared with patients with high educational attainment. The potential mediators
      included in the study, however, did not have a significant mediation effect.
      CONCLUSION: Our study demonstrated a variety of mechanisms contributing to
      cardiac rehabilitation non-attendance. Further, the study demonstrated that non
      attendance was especially related to the cardiac rehabilitation elements
      involving lifestyle modifications. However, the mechanisms explaining social
      inequality in full cardiac rehabilitation are still not fully understood.

PMID- 29185800
TI  - Eight Novel Mutations of the ADAR1 Gene in Chinese Patients with Dyschromatosis
      Symmetrica Hereditaria.
AB  - AIMS: To identify potential novel gene mutations in Chinese patients with
      dyschromatosis symmetrica hereditaria (DSH). METHODS: We enrolled 8 Chinese
      patients with familial DSH, 5 Chinese patients with sporadic DSH, and 100
      randomly selected healthy individuals in this study. The genome of each
      participant was extracted from peripheral blood samples. Sanger sequencing of the
      ADAR1 gene was performed after polymerase chain reaction amplifications.
      Comparisons between the DNA sequences of the affected individuals and the NCBI
      database were performed. RESULTS: We detected eight novel heterozygous mutations
      and five previously reported mutations in the ADAR1 gene in our patients. The
      novel mutations include c.1934 + 3A>G, c.2749A>G, c.2311insA, c.3233G>A, c.3019 +
      1G>T, c.2894C>A, c.1202_1205del, and c.2280C>A. These detected novel mutations
      are predicted to induce two frame-shift mutations, one nonsense mutation, three
      missense mutations, and two splice-site mutations. CONCLUSIONS: The findings of
      this study expand our knowledge of the range of ADAR1 gene mutations in DSH and
      will contribute to identifying correlations between the various DSH phenotypes
      and genotypes. Furthermore, they may provide insight into the underlying
      pathogenic mechanism.

PMID- 29185801
TI  - The Pre-Exposure Prophylaxis-Stigma Paradox: Learning from Canada's First Wave of
      PrEP Users.
AB  - With the emergence of daily oral tenofovir disoproxil fumarate and emtricitabine
      based pre-exposure prophylaxis (PrEP) use in Canada, questions have emerged
      concerning the impacts of this HIV prevention tool on gay men's social and sexual
      lives. We conducted small focus groups and individual qualitative interviews with
      16 gay men in Toronto who were part of the 'first wave' of Canadian PrEP users.
      Participants were on PrEP for at least one year as part of a demonstration
      project (November 2014-June 2016). These participants accessed PrEP before
      regulatory approval by Health Canada in February 2016. The mean age of
      participants was 37.6 years (SD 11.02); 94% completed secondary education, and
      69% were white. Sex-stigma emerged as a complex theme in men's accounts of PrEP
      use across three overlapping domains: (1) PrEP-related stigma, including
      discussions of concealment and stigma from friends, family, and sexual partners,
      (2) PrEP as a perceived tool for combating HIV-related stigma, where some men
      said that they no longer discussed HIV status with sexual partners, and (3) PrEP
      as illuminating structural stigma, where it was attributed to unmasking stigma
      related to sex and sexuality. For some participants, PrEP has allowed for
      liberating sex and a self-described return to normalcy-normal, exciting,
      pleasurable sex that was no longer reliant on condom use. Paradoxically, some men
      said that PrEP use both led them to experience stigmatizing reactions within
      their social and sexual networks, while also helping to remove stigma, shame, and
      fear related to HIV, sexuality, and sex with gay men living with HIV.

PMID- 29185802
TI  - Effects of Cupping Therapy in Amateur and Professional Athletes: Systematic
      Review of Randomized Controlled Trials.
AB  - OBJECTIVE: Despite the recent re-emergence of the process of cupping by athletes,
      supporting evidence for its efficacy and safety remains scarce. This systematic
      review aims to summarize the evidence of clinical trials on cupping for athletes.
      METHODS: SCOPUS, Cochrane Library, PubMed, AMED, and CNKI databases were searched
      from their inception to December 10, 2016. Randomized controlled trials on
      cupping therapy with no restriction regarding the technique, or cointerventions,
      were included, if they measured the effects of cupping compared with any other
      intervention on health and performance outcomes in professionals, semi
      professionals, and leisure athletes. Data extraction and risk of bias assessment
      using the Cochrane Risk of Bias Tool were conducted independently by two pairs of
      reviewers. RESULTS: Eleven trials with n = 498 participants from China, the
      United States, Greece, Iran, and the United Arab Emirates were included,
      reporting effects on different populations, including soccer, football, and
      handball players, swimmers, gymnasts, and track and field athletes of both
      amateur and professional nature. Cupping was applied between 1 and 20 times, in
      daily or weekly intervals, alone or in combination with, for example,
      acupuncture. Outcomes varied greatly from symptom intensity, recovery measures,
      functional measures, serum markers, and experimental outcomes. Cupping was
      reported as beneficial for perceptions of pain and disability, increased range of
      motion, and reductions in creatine kinase when compared to mostly untreated
      control groups. The majority of trials had an unclear or high risk of bias. None
      of the studies reported safety. CONCLUSIONS: No explicit recommendation for or
      against the use of cupping for athletes can be made. More studies are necessary
      for conclusive judgment on the efficacy and safety of cupping in athletes.

PMID- 29185803
TI  - Better Tolerance of Citalopram in a Breastfed Infant Who Could Not Tolerate
      Sertraline and Paroxetine.
AB  - Postpartum depression is frequently observed in women. First-line antidepressants
      in treatment of postpartum depression are selective serotonin reuptake inhibitors
      (SSRIs). Although SSRIs are well tolerated by most breastfed infants, some
      adverse events may arise in exposed infants. This report presents the case of an
      infant of a breastfeeding woman using citalopram without any problem after
      sertraline and paroxetine were discontinued due to adverse events in the infant.

PMID- 29185804
TI  - Theory of Morphogenesis.
AB  - A model of morphogenesis is proposed based on seven explicit postulates. The
      mathematical import and biological significance of the postulates are explored
      and discussed.

PMID- 29185805
TI  - An Optimized Method for Bayesian Connectivity Change Point Model.
AB  - The brain undergoes functional dynamic changes at all times. Investigating
      functional dynamics has been recently verified to be helpful for detecting
      psychological conditions and powerful for analyzing disease-related abnormalities
      of the brain. This article aims to detect functional dynamics. Specifically, we
      focus on how to effectively distinguish corresponding functional connectivity and
      change points from functional magnetic resonance imaging (fMRI) data. By
      combining Bayesian connectivity change point model (BCCPM), a modified genetic
      algorithm (GA) is presented to optimize the evolutionary procedure toward the
      most probable distributions of real change points in fMRI. We randomly initialize
      different binary indicator vectors to represent different distributions of change
      points. Each indicator vector represents an individual in GA, and together they
      form an initial population. Then we calculate Bayesian posterior probability and
      use it as the fitness of each individual. Finally, we evolve individuals of
      current generation toward the next higher fitness generation by a series of
      modified genetic operators. After several evolutionary procedures, individuals in
      the final generation may have outstanding fitness and the one with highest
      fitness can represent the most likely change point distribution in the
      corresponding fMRI data. Furthermore, the most probable change point distribution
      could be resolved. We test the optimized method for BCCPM on several synthesized
      data sets, and the experimental results verify that the proposed model produces
      higher accuracy results with lower time consumption. Also, we apply the new model
      to real block-designed task-based fMRI data set and excellent results are
      obtained.

PMID- 29185807
TI  - ICON-MIC: Implementing a CPU/MIC Collaboration Parallel Framework for ICON on
      Tianhe-2 Supercomputer.
AB  - Electron tomography (ET) is an important technique for studying the three
      dimensional structures of the biological ultrastructure. Recently, ET has reached
      sub-nanometer resolution for investigating the native and conformational dynamics
      of macromolecular complexes by combining with the sub-tomogram averaging
      approach. Due to the limited sampling angles, ET reconstruction typically suffers
      from the "missing wedge" problem. Using a validation procedure, iterative
      compressed-sensing optimized nonuniform fast Fourier transform (NUFFT)
      reconstruction (ICON) demonstrates its power in restoring validated missing
      information for a low-signal-to-noise ratio biological ET dataset. However, the
      huge computational demand has become a bottleneck for the application of ICON. In
      this work, we implemented a parallel acceleration technology ICON-many integrated
      core (MIC) on Xeon Phi cards to address the huge computational demand of ICON.
      During this step, we parallelize the element-wise matrix operations and use the
      efficient summation of a matrix to reduce the cost of matrix computation. We also
      developed parallel versions of NUFFT on MIC to achieve a high acceleration of
      ICON by using more efficient fast Fourier transform (FFT) calculation. We then
      proposed a hybrid task allocation strategy (two-level load balancing) to improve
      the overall performance of ICON-MIC by making full use of the idle resources on
      Tianhe-2 supercomputer. Experimental results using two different datasets show
      that ICON-MIC has high accuracy in biological specimens under different noise
      levels and a significant acceleration, up to 13.3 * , compared with the CPU
      version. Further, ICON-MIC has good scalability efficiency and overall
      performance on Tianhe-2 supercomputer.

PMID- 29185806
TI  - Workplace Breastfeeding Support Varies by Employment Type: The Service Workplace
      Disadvantage.
AB  - BACKGROUND: The majority of women are returning to work full-time after
      childbirth, and support within their place of employment may influence intention
      and duration for breastfeeding, but more research is needed. Therefore, the
      purpose of this study was to explore the influence of employment type on
      breastfeeding duration upon return to work by examining informal (i.e., verbal
      encouragement) and direct (i.e., lactation space, flexible time) factors of
      support. METHODS: This was a retrospective survey of women's returning-to-work
      experiences while breastfeeding. Survey contents included respondent demographics
      as well as questions surrounding perceptions of employer support, work
      environment, and goal/satisfaction regarding breastfeeding. Data were analyzed
      via crosstabs and chi-square goodness of fit tests. RESULTS: A total of 1,002
      women completed the survey. Significant differences were seen across different
      employment types. Women within the professional/management industry were most
      likely to receive informal and direct support for breastfeeding upon return to
      work. Women within the service industry and production/transportation industry
      reported receiving the lowest levels of informal and direct support. CONCLUSION:
      Workplace support varies by employment type and women in the service and
      production/transportation industry appear to be at a disadvantage compared with
      other employment types. There is a need for more breastfeeding support programs
      to be developed that target specific workplace characteristics.

PMID- 29185808
TI  - Lipid-modifying activity of curcuminoids: A systematic review and meta-analysis
      of randomized controlled trials.
AB  - OBJECTIVE: The aim of this systematic review and meta-analysis was to determine
      and clarify the impact of curcuminoids on serum lipid levels. METHODS: Randomized
      controlled trials (RCTs) investigating the effects of curcuminoids on plasma
      lipids were searched in PubMed-Medline, Scopus, Web of Science databases (from
      inception to April 3rd, 2017). A random-effects model and generic inverse
      variance method were used for quantitative data synthesis. Sensitivity analysis
      was conducted using the leave-one-out method. A weighted random-effects meta
      regression was performed to evaluate the impact of potential confounders on lipid
      concentrations. RESULTS: A meta-analysis of 20 RCTs with 1427 participants
      suggested a significant decrease in plasma concentrations of triglycerides (WMD: 
      21.36 mg/dL, 95% CI: -32.18, -10.53, p < 0.001), and an elevation in plasma HDL-C
      levels (WMD: 1.42 mg/dL, 95% CI: 0.03, 2.81, p = 0.046), while plasma levels of
      LDL-C (WMD: -5.82 mg/dL, 95% CI: -15.80, 4.16, p = 0.253) and total cholesterol
      (WMD: -9.57 mg/dL, 95% CI: -20.89, 1.75, p = 0.098) were not altered. The effects
      of curcuminoids on lipids were not found to be dependent on the duration of
      supplementation. CONCLUSION: This meta-analysis has shown that curcuminoid
      therapy significantly reduces plasma triglycerides and increases HDL-C levels.

PMID- 29185809
TI  - Spatial memory recovery in Alzheimer's rat model by electromagnetic field
      exposure.
AB  - INTRODUCTION: Although studies have shown a potential association between
      extremely low frequency electromagnetic fields (ELF-EMFs) exposure and
      Alzheimer's disease (AD), few studies have been conducted to investigate the
      effects of weak magnetic fields on brain functions such as cognitive functions in
      animal models. Therefore, this study aimed to investigate the effect of ELF-EMF
      exposure (50 Hz, 10 mT) on spatial learning and memory changes in AD rats.
      METHODS: Amyloid-beta (Abeta) 1-42 was injected into lateral ventricle to
      establish an AD rat model. The rats were divided into six groups: Group I
      (control); Group II (surgical sham); Group III (AD) Alzheimer's rat model; Group
      IV (MF) rats exposed to ELF-MF for 14 consecutive days; Group V (Abeta
      injection+M) rats exposed to magnetic field for 14 consecutive days from day 0 to
      14 days after the Abeta peptide injection; Group VI (AD+M) rats exposed to
      magnetic field for 14 consecutive days after 2 weeks of Abeta peptide injection
      from 14th to 28th day . Morris water maze investigations were performed. RESULTS:
      AD rats showed a significant impairment in learning and memory compared to
      control rats. The results showed that ELF-MF improved the learning and memory
      impairments in Abeta injection+M and AD+M groups. CONCLUSION: Our results showed
      that application of ELF-MF not only has improving effect on different cognitive
      disorder signs of AD animals, but also disrupts the processes of AD rat model
      formation.

PMID- 29185810
TI  - Investigation Into the Optimal Number of Intercostal Nerve Transfers for
      Musculocutaneous Nerve Reinnervation: A Systematic Review.
AB  - BACKGROUND: The purpose of this study was to systematically review outcomes
      following intercostal nerve (ICN) transfer for restoration of elbow flexion, with
      a focus on identifying the optimal number of nerve transfers. METHODS: A
      systematic review was performed following Preferred Reporting Items for
      Systematic Reviews and Meta-analyses (PRISMA) guidelines to identify studies
      describing ICN transfers to the musculocutaneous nerve (MCN) for traumatic
      brachial plexus injuries in patients 16 years or older. Demographics were
      recorded, including age, time to operation, and level of brachial plexus injury.
      Muscle strength was scored based upon the British Medical Research Council scale.
      RESULTS: Twelve studies met inclusion criteria for a total of 196 patients.
      Either 2 (n = 113), 3 (n = 69), or 4 (n = 11) ICNs were transferred to the MCN in
      each patient. The groups were similar with regard to patient demographics. Elbow
      flexion >=M3 was achieved in 71.3% (95% confidence interval [CI], 61.1%-79.7%) of
      patients with 2 ICNs, 67.7% (95% CI, 55.3%-78.0%) of patients with 3 ICNs, and
      77.0% (95% CI, 44.9%-93.2%) of patients with 4 ICNs ( P = .79). Elbow flexion
      >=M4 was achieved in 51.1% (95% CI, 37.4%-64.6%) of patients with 2 ICNs, 42.1%
      (95% CI, 29.5%-55.9%) of patients with 3 ICNs, and 48.4% (95% CI, 19.2%-78.8%) of
      patients with 4 ICNs ( P = .66). CONCLUSIONS: Previous reports have described 2.5
      times increased morbidity with each additional ICN harvest. Based on the
      equivalent strength of elbow flexion irrespective of the number of nerves
      transferred, 2 ICNs are recommended to the MCN to avoid further donor-site
      morbidity.

PMID- 29185811
TI  - Welfare impacts of the illegal wildlife trade in a cohort of confiscated greater
      slow lorises, Nycticebus coucang.
AB  - Illegal harvesting and trade are major forces behind population declines of wild
      slow lorises (genus Nycticebus). The impacts of the wildlife trade on individual
      slow lorises have not been as well described. In this article, we describe
      quantitatively the consequences of the wildlife trade for 77 greater slow
      lorises, N. coucang, who were confiscated en masse and brought to Cikananga
      Wildlife Center in Indonesia. Medical records indicated that in total, 28.6% of
      the slow lorises died within the first 6 months, mostly due to traumatic injury,
      and all the infants died. The greatest sources of morbidity were external wounds
      (33.1% of 166 total medical events) and dental problems (19.3%). Of the surviving
      individuals, 25.4% displayed abnormal behavior. Behavioral observations indicated
      that healthy adults (n = 3) spent 48.2% of their active period performing
      stereotypies. These data illustrate the physical and behavioral impacts of the
      illegal wildlife trade on the welfare of slow lorises. We suggest that sharing
      these individual stories may help generate empathy and educate the public about
      the impacts of the exotic companion-animal (pet) trade on nonhuman animal
      welfare.

PMID- 29185813
TI  - The Trapezium Dislocation: Case Presentation, Review of the Literature,
      Radiographic Analysis, Proposed Classification, and Treatment.
AB  - BACKGROUND: Trapezium dislocations are rare injuries. METHODS: A PubMed search of
      the term "trapezium dislocation" was conducted. Publications reporting a complete
      trapezium dislocation were included in the review. RESULTS: The PubMed search
      resulted in 168 results. Fourteen publications reporting on 16 complete trapezium
      dislocations met inclusion criteria. A case of delayed diagnosis of a trapezium
      dislocation is presented. The literature is reviewed for pertinent clinically
      relevant information with respect to trapezium dislocations. A systematic method
      for radiographic analysis of trapezium dislocations and classification are
      described, and a treatment algorithm is presented. CONCLUSIONS: Trapezium
      dislocations are infrequent injuries with few cases reported in the literature.
      Given the rarity of this injury, diagnosis and appropriate treatment may be
      delayed due to difficulty in recognition. Using the described method of
      radiographic analysis, delayed diagnosis may be avoided with implementation of
      timely treatment.

PMID- 29185812
TI  - Brand and generic use of inhalation medication and frequency of switching in
      children and adults: A population-based cohort study.
AB  - BACKGROUND: The expiration of patents of brand inhalation medications and the
      ongoing pressure on healthcare budgets resulted in a growing market for generics.
      AIM: To study the use of brand and generic inhalation medication and the
      frequency of switching between brand and generic and between devices. In
      addition, we investigated whether switching affected adherence. METHODS: From
      dispensing data from the Dutch PHARMO Database Network a cohort aged >= 5 years,
      using >= 1 year of inhalation medication between 2003 and 2012 was selected.
      Switching was defined as changing from brand to generic or vice versa. In
      addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and
      nebulizers). Adherence was calculated using the medication possession ratio
      (MPR). RESULTS: The total cohort comprised 70,053 patients with 1,604,488
      dispensations. Per calendar year, 5% switched between brand and generic
      inhalation medication and 5% switched between devices. Median MPRs over the first
      12 months ranged between 33 and 55%. Median MPR over the total period was lower
      after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1
      and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9).
      CONCLUSION: Per year, switching between brand and generic inhalation medication
      was limited to 5% of the patients, switching between device types was observed in
      5% as well. Adherence to both generic and brand inhalation medication was low.
      Effect of switching on adherence was contradictory; depending on time period,
      medication and type, and direction of switching. Further research on reasons for
      switching and potential impact on clinical outcomes is warranted.

PMID- 29185814
TI  - Pupil Dilation May Affect Retinal Vessel Caliber Measures.
AB  - PURPOSE: To assess the effect of pupil dilation on measures of retinal vessel
      caliber. DESIGN: Observational study with self-comparisons Methods: Retinal
      photographs were taken for both eyes of 25 subjects before and after pupil
      dilation. Three photographic graders, masked to pupil dilation status, measured
      the same set of images using a computer-assisted, semi-automatic method. We
      compared means (standard deviations) of retinal arteriolar caliber equivalent
      (CRAE) and retinal venular caliber equivalent (CRVE) of the same eyes between pre
      and post-dilation images. We assessed concordance correlation coefficients (CC),
      Bland Altman limits-of-agreements, and used linear mixed models to assess CRAE
      and CRVE measures associated with pupil dilation (influencing image quality),
      graders (observers) and right-left eye variation. RESULTS: We found high CCs for
      CRAE (0.82-0.94) and CRVE (0.87-0.94) between pre- and post-dilation images of
      the same eyes across the graders. Bland Altman plots showed that mean differences
      ranged from 0.55-3.42MUm for CRAE and 1.56-2.29MUm for CRVE. After adjusting for
      right-left eye random variation, a significant fixed effect of dilation was
      evident in mean CRAE in two of the three graders. There was no significant fixed
      effect of dilation in mean CRVE across all graders. In models including data of
      both eyes' measures from pre- and post-dilation images by three graders, the
      fixed effect for dilation status contributed significantly to CRAE and CRVE
      variances whereas random effects for graders and dilation status contributed
      minimally. CONCLUSIONS: Contrary to our hypothesis, we found a systematic effect
      of pupil dilation on retinal vessel caliber measures.

PMID- 29185815
TI  - 2016 Annual Report of the American Association of Poison Control Centers'
      National Poison Data System (NPDS): 34th Annual Report.
AB  - INTRODUCTION: This is the 34th Annual Report of the American Association of
      Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1
      January 2016, 55 of the nation's poison centers (PCs) uploaded case data
      automatically to NPDS. The upload interval was 9.50 [7.33, 14.6] (median [25%,
      75%]) min, facilitating a near real-time national exposure and information
      database and surveillance system. METHODS: We analyzed the case data tabulating
      specific indices from NPDS. The methodology was similar to that of previous
      years. Where changes were introduced, the differences are identified. Cases with
      medical outcomes of death were evaluated by a team of medical and clinical
      toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative
      Contribution to Fatality (RCF) of the exposure. RESULTS: In 2016, 2,710,042
      closed encounters were logged by NPDS: 2,159,032 human exposures, 54,019 animal
      exposures, 490,215 information cases, 6687 human confirmed non-exposures, and 89
      animal confirmed non-exposures. US PCs also made 2,718,022 follow-up calls in
      2016. Total encounters showed a 2.94% decline from 2015, while health care
      facility (HCF) human exposure cases increased by 3.63% from 2015. All information
      calls decreased by 12.5% but HCF information calls increased 0.454%, and while
      medication identification requests (Drug ID) decreased 29.6%, human exposure
      cases were essentially flat, decreasing by 0.431%. Human exposures with less
      serious outcomes have decreased 2.59% per year since 2008 while those with more
      serious outcomes (moderate, major or death) have increased by 4.39% per year
      since 2000. The top five substance classes most frequently involved in all human
      exposures were analgesics (11.2%), household cleaning substances (7.54%),
      cosmetics/personal care products (7.20%), sedatives/hypnotics/antipsychotics
      (5.84%), and antidepressants (4.74%). As a class,
      sedative/hypnotics/antipsychotics exposures increased most rapidly, by 10.7% per
      year (2088 cases/year), over the last 15 years for cases showing more serious
      outcomes. The top five most common exposures in children age 5 years or less were
      cosmetics/personal care products (13.3%), household cleaning substances (11.1%),
      analgesics (9.21%), foreign bodies/toys/miscellaneous (6.48%), and topical
      preparations (5.07%). Drug identification requests comprised 28.1% of all
      information calls. NPDS documented 1977 human exposures resulting in death; 1492
      (75.5%) of these were judged as related (RCF of 1 - undoubtedly responsible, 2 -
      probably responsible, or 3 - contributory). CONCLUSIONS: These data support the
      continued value of PC expertise and need for specialized medical toxicology
      information to manage more serious exposures, despite a decrease in cases
      involving less serious exposures. Unintentional and intentional exposures
      continue to be a significant cause of morbidity and mortality in the US. The near
      real-time, always current status of NPDS represents a national public health
      resource for collecting and monitoring US exposure cases and information calls.
      The continuing mission of NPDS is to provide a nationwide infrastructure for
      surveillance for all types of exposures (e.g. foreign body, infectious, venomous,
      chemical agent, or commercial product), and the identification and tracking of
      significant public health events. NPDS is a model system for the real-time
      surveillance of national and global public health.

PMID- 29185817
TI  - Does Religious Attendance Moderate the Connection between Pornography Consumption
      and Attitudes toward Women?
AB  - Feminist theory and religious doctrines alike often suggest that pornography
      alters the attitudes of those who consume it, particularly with respect to how
      consumers view women. Many would assume that pornography would universally
      encourage sexism and female objectification, but recent evidence has linked
      pornography use with more gender egalitarian views. Using data from a large
      scale, nationally representative survey, we argue that cognitive dissonance among
      pornography consumers could alter egalitarian attitudes. We found that those who
      reported consuming pornography had more egalitarian attitudes than those who did
      not, but this difference was stronger among those who attended religious services
      more regularly-those who would be likely to experience dissonance when consuming
      pornography. This pattern was consistent across the three egalitarian attitudes
      we examined: attitudes toward women in power, women in the workplace, and
      abortion. Our results suggest that pornography might foster progressive attitudes
      among those most likely to hold conservative beliefs.

PMID- 29185816
TI  - Measurements of Retinal Nerve Fiber Thickness and Ganglion Cell Complex in
      Neurofibromatosis Type 1, with and Without Optic Pathway Gliomas: A Case Series.
AB  - PURPOSE: The aim of this study was to investigate differences in retinal nerve
      fiber layer (RNFL) and ganglion cell complex (GCC) thicknesses in
      neurofibromatosis 1 (NF1) cases, with and without optic pathway gliomas (OPGs).
      MATERIALS AND METHODS: In total, 33 eyes of 33 subjects were evaluated in this
      prospective observational case series. Twenty-one patients with a diagnosis of
      NF1 were enrolled. Patients with NF1 and OPGs were included in Group 1 (n = 9),
      and patients with NF1 without OPGs were included in Group 2 (n = 12). The control
      group (Group 3) was comprised of 12 age- and sex-matched subjects with no history
      of ophthalmic or systemic diseases. All of the subjects underwent complete
      ophthalmic examinations, including best-corrected visual acuity (BCVA), slit lamp
      microscopy, and indirect ophthalmoscopy. Additionally, optical coherence
      tomography (OCT) measurements were obtained. RESULTS: There were no statistically
      significant between-group differences in age and sex (p = 0.227 and 0.986,
      respectively). The average RNFL thickness in Group 1 (NF1 patients with OPGs) was
      significantly lower than in Groups 2 and 3 (86.6 +/- 22.5, 107.4 +/- 6.65, and
      108.4 +/- 5.05 um, respectively; p = 0.001). Furthermore, the average GCC
      thickness in Group 1 was significantly lower than in Groups 2 and 3 (78.6 +/-
      16.3, 94.8 +/- 3.55, and 94.9 +/- 3.82 um, respectively; p < 0.001). CONCLUSIONS:
      Both RNFL and GCC thicknesses were significantly lower in NF1 patients with OPGs.
      The use of OCT to quantify damage to the visual pathway may enable earlier
      detection of OPGs in NF1 patients.

PMID- 29185818
TI  - Teaming With a Synthetic Teammate: Insights into Human-Autonomy Teaming.
AB  - Objective Three different team configurations are compared with the goal of
      better understanding human-autonomy teaming (HAT). Background Although an
      extensive literature on human-automation interaction exists, much less is known
      about HAT in which humans and autonomous agents interact as coordinated units.
      Further research must be conducted to better understand how all-human teams
      compare to HAT. Methods In an unmanned aerial system (UAS) context, a comparison
      was made among three types of three-member teams: (1) synthetic teams in which
      the pilot role is assigned to a synthetic teammate, (2) control teams in which
      the pilot was an inexperienced human, and (3) experimenter teams in which an
      experimenter served as an experienced pilot. Ten of each type of team
      participated. Measures of team performance, target processing efficiency, team
      situation awareness, and team verbal behaviors were analyzed. Results Synthetic
      teams performed as well at the mission level as control (all human) teams but
      processed targets less efficiently. Experimenter teams performed better across
      all other measures compared to control and synthetic teams. Conclusion Though
      there is potential for a synthetic agent to function as a full-fledged teammate,
      further advances in autonomy are needed to improve team-level dynamics in HAT
      teams. Application This research contributes to our understanding of how to make
      autonomy a good team player.

PMID- 29185819
TI  - Reversal of Glanzmann thrombasthenia platelet phenotype after imatinib treatment
      in a pediatric chronic myeloid leukemia patient.
AB  - Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm characterized
      by proliferation of Philadelphia positive clonal pluripotent hematopoietic cells.
      Bleeding is a rare presentation of CML that can occur due to platelet
      dysfunction. Both pre-treatment and post-treatment platelet function
      abnormalities in CML have been described in the literature. We describe a rare
      case of childhood CML who presented with mucocutateous bleeding manifestations.
      On laboratory workup, a Glanzmann Thrombasthenia (GT) like platelet phenotype was
      demonstrated along with confirmation of diagnosis of CML in chronic phase. The
      acquired nature of platelet function defect was confirmed by demonstrating
      recovery of platelet antigens glycoprotein IIb/IIIa after achieving complete
      hematological response with Imatinib. Due to presenting complaint of bleeding
      diathesis and absence of hepatosplenomegaly, the case was undiagnosed for CML
      until the patient reported to us. Careful evaluation of complete blood counts,
      peripheral blood picture and detailed laboratory workup was the window to proper
      diagnosis and treatment in this case.

PMID- 29185820
TI  - Delusional misidentification in Parkinson's disease: report of two cases and a
      review.
AB  - Syndromes of delusional misidentification consist of disordered familiarity and
      have been reported in diverse diagnoses, including Parkinson's disease. Although
      the most common delusional misidentification is Capgras syndrome, in which the
      sufferer believes a familiar person has been replaced by an identical imposter,
      other forms have been also described. The pathogenesis of delusions of
      misidentification appears to require dysfunction of or connection to a left
      cerebral cortical area involved in recognition of familiarity, and also right
      frontal cortex serving belief evaluation. Two cases of Parkinson's disease with
      an unusual delusional misidentification, intermetamorphosis, are presented, along
      with their improvement with pimavanserin, a novel atypical antipsychotic
      medication.

PMID- 29185821
TI  - Neurocognitive and neurodevelopmental impact of prenatal methamphetamine
      exposure: A comparison study of prenatally exposed children with nonexposed ADHD
      peers.
AB  - Prenatal methamphetamine exposure has become an increasingly pervasive concern,
      especially in rural-based populations and populations of lower socioeconomic
      status. While research has begun to highlight the effects of prenatal
      methamphetamine exposure, the long-term impact of this exposure remains an under
      investigated topic. This study attempts to investigate the neurocognitive and
      neurodevelopmental effects of prenatal methamphetamine exposure by comparing the
      index and full-scale IQ scores on the WISC-IV between a sample of clinically
      referred children prenatally exposed to methamphetamine (N = 80) and a sample of
      clinically referred nonexposed children diagnosed with ADHD (N = 44). Children
      prenatally exposed to methamphetamine showed significantly lower scores on all
      WISC-IV domains when compared to peers with ADHD. When taking into account
      polysubstance exposure to alcohol, these differences remained statistically
      significant, with the exception of the Processing Speed Index (PSI); children
      reported to have been prenatally exposed to methamphetamine and to alcohol (PME)
      remained below ADHD peers on all other WISC-IV index scores. Within the
      prenatally exposed sample, regression analyses indicated that age was a
      significant negative predictor of PSI scores. Overall findings suggest that
      prenatal methamphetamine exposure is associated with a notable cognitive impact
      independent of polysubstance exposure to alcohol, and that the impact of this
      exposure on processing speed skills may become more pronounced with age.

PMID- 29185822
TI  - Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in
      real-world clinical practice: interim results of the STELLA-LONG TERM post
      marketing surveillance study.
AB  - BACKGROUND: Data regarding the efficacy and safety of sodium-glucose
      cotransporter 2 inhibitors in the real-world setting in Japan are limited. The
      STELLA-LONG TERM study is an ongoing 3-year post-marketing surveillance study of
      ipragliflozin in type 2 diabetes (T2D) patients. Here, we report the interim
      results (including 3-, 12-, and 24-month data). RESEARCH DESIGN AND METHODS: All
      Japanese patients with T2D who were first prescribed ipragliflozin between 17
      July 2014 and 16 October 2015 at participating centers in Japan were registered
      in STELLA-LONG TERM. RESULTS: At 3, 12, and 24 months, the safety analysis set
      comprised 11,053, 5475, and 138 patients, respectively; the efficacy analysis set
      comprised 8757 patients. Ipragliflozin treatment resulted in statistically
      significant improvements versus baseline in hemoglobin A1c, fasting plasma
      glucose concentration, body weight, blood pressure, heart rate, and serum
      concentrations of low-density lipoprotein cholesterol and triglycerides. The
      adverse drug reaction incidence rate was 10.71%, the most common reactions being
      renal and urinary disorders (5.06%), infections and infestations (1.24%), and
      skin and subcutaneous tissue disorders (1.14%). CONCLUSIONS: Ipragliflozin was
      well tolerated and effective in Japanese patients with T2D; no new safety issues
      were identified.

PMID- 29185823
TI  - Texas Mexican American adult normative studies: Normative data for the Repeatable
      Battery for the Assessment of Neuropsychological Status (RBANS).
AB  - The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is
      an assessment of neuropsychological functioning commonly used in clinical and
      research settings. To our knowledge, normative data for the RBANS is not
      available for Hispanic, Mexican Americans, which the current study sought to
      establish. Data from 136 Hispanic, Mexican Americans from Project FRONTIER were
      analyzed. Approximately half of the sample was administered testing in Spanish.
      Normative tables were created for English and Spanish speaking Mexican Americans.
      Generated RBANS normative references are provided for unadjusted raw scores as
      well as output adjusted by education level.

PMID- 29185824
TI  - Comparison Between High-Pressure Processing and Chemical Extraction: Astaxanthin
      Yield From Six Species of Shrimp Carapace.
AB  - Astaxanthin is one of the main carotenoid pigments. It has beneficial effects on
      the immune system of the human body due to its powerful antioxidant properties.
      The application of this bioactive compound can be found to be significant in the
      food, pharmaceutical, and cosmetics industries. The aim of this research was to
      investigate astaxanthin yield from six species of Malaysian shrimp carapace. Six
      types of shrimp species-Parapenaeopsis sculptili, Metapenaeus lysianassa,
      Macrobrachium rosenbergii, Metapenaeopsis hardwickii, Penaeus merguiensis, and
      Penaeus monodon-were used to investigate total carotenoid content and astaxanthin
      yield. The investigation was carried out using chemical extraction and high
      pressure processing (HPP) methods at 210 MPa, for a period of 10 min with a
      solvent mixture of acetone and methanol (7:3, v/v). HPP was proven to have a
      significant impact in increasing the total carotenoid content and astaxanthin
      yield. The highest total carotenoid content and astaxanthin yield is shown to be
      contained in the Penaeus monodon species. Total carotenoid was increased from
      46.95 ug/ml using chemical extraction to 68.26 ug/ml using HPP; yield of
      astaxanthin was increased from 29.44 ug/gdw using chemical extraction to 59.9744
      ug/gdw using HPP. Therefore, comparison between the HPP and chemical extraction
      methods showed that HPP is more advantageous with higher astaxanthin yield,
      higher quality, and shorter extraction time.

PMID- 29185825
TI  - Effect of Probiotic Supplementation on CD4 Cell Count in HIV-Infected Patients: A
      Systematic Review and Meta-analysis.
AB  - Progressive decline in CD4 cell counts is associated with human immunodeficiency
      virus (HIV) disease progression. Loss of CD4 cells might contribute to gut
      microbiota alteration and bacterial translocation. Probiotics, by inducing
      epithelial healing, may promote the restoration of the intestinal CD4+ T-cell
      population. The aim of this meta-analysis was to systematically review all
      randomized controlled trials (RCTs) of probiotic/prebiotic/synbiotic
      supplementation on CD4 cell counts in HIV-infected patients. A systematic search
      of RCTs was conducted through PubMed, Scopus, and Google Scholar databases up to
      August 2015. Effect sizes of eligible studies were pooled using random-effects
      models (the DerSimonian-Laird estimator). Eleven studies with 14 treatment arms
      met the inclusion criteria. Pooled analysis showed no significant reduction in
      CD4 counts (-7.5 mg/l, p = .7) in intervention-treated individuals. Subgroup
      analysis on potential influencing factors highlighted sex, country of origin,
      study duration, and the type of intervention as having significant effects on CD4
      cell counts. As a whole, the results of this meta-analysis suggested that
      supplementation with probiotic may not change CD4 counts. However, a significant
      increase in CD4 counts was seen in females and following synbiotics as opposed to
      treatment with pro- or prebiotics alone.

PMID- 29185826
TI  - Series: Practical guidance to qualitative research. Part 2: Context, research
      questions and designs.
AB  - In the course of our supervisory work over the years, we have noticed that
      qualitative research tends to evoke a lot of questions and worries, so-called
      frequently asked questions (FAQs). This series of four articles intends to
      provide novice researchers with practical guidance for conducting high-quality
      qualitative research in primary care. By 'novice' we mean Master's students and
      junior researchers, as well as experienced quantitative researchers who are
      engaging in qualitative research for the first time. This series addresses their
      questions and provides researchers, readers, reviewers and editors with
      references to criteria and tools for judging the quality of qualitative research
      papers. This second article addresses FAQs about context, research questions and
      designs. Qualitative research takes into account the natural contexts in which
      individuals or groups function to provide an in-depth understanding of real-world
      problems. The research questions are generally broad and open to unexpected
      findings. The choice of a qualitative design primarily depends on the nature of
      the research problem, the research question(s) and the scientific knowledge one
      seeks. Ethnography, phenomenology and grounded theory are considered to represent
      the 'big three' qualitative approaches. Theory guides the researcher through the
      research process by providing a 'lens' to look at the phenomenon under study.
      Since qualitative researchers and the participants of their studies interact in a
      social process, researchers influence the research process. The first article
      described the key features of qualitative research, the third article will focus
      on sampling, data collection and analysis, while the last article focuses on
      trustworthiness and publishing.

PMID- 29185827
TI  - Eugenics, medicine and psychiatry in Peru.
AB  - Eugenics was defined by Galton as 'the science which deals with all influences
      that improve the inborn qualities of a race'. In Peru, eugenics was related to
      social medicine and mental hygiene, in accordance with the neo-Lamarckian
      orientation, that predominated in Latin America. Peruvian eugenists assumed the
      mission of fighting hereditary and infectious diseases, malnutrition, alcoholism,
      drug addiction, prostitution, criminality and everything that threatened the
      future of the 'Peruvian race'. There were some enthusiastic advocates of 'hard'
      eugenic measures, such as forced sterilization and eugenic abortion, but these
      were never officially implemented in Peru (except for the compulsory
      sterilization campaign during the 1995-2000 period). Eugenics dominated
      scientific discourse during the first half of the twentieth century, but eugenic
      discourse did not disappear completely until the 1970s.

PMID- 29185828
TI  - Increased prevalence of depression and anxiety among subjects with metabolic
      syndrome and known type 2 diabetes mellitus - a population-based study.
AB  - OBJECTIVES: The metabolic syndrome (MetS) is a cluster of cardiovascular risk
      factors associated with high cardiovascular morbidity and mortality. The MetS and
      its elements have been linked to anxiety and depressive disorders. The aim of the
      current cross-sectional study was to assess the prevalence of depression and
      anxiety, measured by the Zung Self-Rating Scale in subjects with and without the
      metabolic syndrome and diabetes. METHODS: A total of 2111 adults were included,
      1155 female, age 47.6 (13.7) and 956 male, age 45.2 (13.5). All participants
      filled questionnaires covering current and past disorders and medication, smoking
      and family history. Zung self-rating depression and anxiety scales were
      completed. Body weight, height and waist circumference were measured, BMI was
      calculated, serum glucose and lipids were measured. RESULTS: Depression (SDSi)
      and anxiety scores (SASi) were higher in the females and increased with age (p <
      0.001). SDSi was higher in the females and males with metabolic syndrome (MetS)
      (50.9 +/- 9.8 vs. 45.9 +/- 8.9, p < 0.001 and 42.7 +/- 9.2 vs. 40.5 +/- 7.9 p <
      0.001, respectively). SASi was higher in the MetS subjects (females 50.59 +/-
      11.35 vs. 45.97 +/- 10.58, p < 0.001; males 40.48 +/- 10.1 vs. 38.04 +/- 8.42, p
      < 0.001). Both SDSi and SASi were higher in the subjects with known diabetes than
      in those with normal glucose tolerance (Mann-Whitney both p < 0,001). Positive
      depressive scores were more prevalent in subjects with MetS than those without
      (females 54% vs. 31.6%, p < 0.001; males 22.7% vs. 12.3%, p < 0.001). Depression
      and anxiety were more prevalent in the subjects with known diabetes than in those
      with normal glucose tolerance but not in the newly-diagnosed diabetes. The OR for
      depressiveness was 2.0 (1.3; 2.6) in subjects with MetS and 4.2 (2.3; 7.8) in
      those with known diabetes. CONCLUSIONS: In conclusion, depressiveness and anxiety
      were associated positively with age and female gender and were more prevalent
      among subjects with MetS and known diabetes mellitus.

PMID- 29185829
TI  - A multi-hospital analysis of predictors of oral anticoagulation prescriptions for
      patients with actionable atrial fibrillation who attend the emergency department.
AB  - Atrial fibrillation (AF) is the most common arrhythmia and is associated with an
      increase in the risk of ischemic stroke. The risk of stroke can be significantly
      decreased by oral anticoagulation (OAC). Our objective was to characterize the
      filling of OAC prescriptions for patients with actionable AF (new or existing AF
      with an indication for OAC but not prescribed) and determine the prevalence and
      predictors of guideline-appropriate therapy at 30 days. This is a multi-hospital,
      retrospective cohort study of patients who visited the Emergency Department (ED)
      and had a discharge diagnosis of AF. Patient records were examined to identify
      demographics, risk factors, and prescription data. Predictors of filling a
      prescription at 30 days were analyzed. 788 patients with AF were reviewed. 257
      patients had actionable AF. Forty one percent (104) had newly diagnosed AF. The
      mean CHADS2 score was 2 +/- 1. At 30 days after discharge, 25.7% of patients
      filled a prescription for OAC therapy. Large numbers of patients attending the ED
      have actionable AF, but rates of guideline-directed OAC at thirty days are low.
      Only a prescription written by the ED physician (OR 9.89) and documentation of
      stroke risk stratification in the patients' chart (OR 4.09) were associated with
      the primary outcome.

PMID- 29185830
TI  - Median Nerve Injury After Removal of Subdermal Implantable Contraceptive.
AB  - BACKGROUND: Subdermal implantable contraceptives are highly effective, approved
      in over 60 countries, and used by millions of women. Due to simple insertion and
      removal protocols, these procedures are often performed in the outpatient clinic
      setting, and procedural complications are rare. However, given the location of
      the implant in the medial antebrachial interval, there is a risk of neurovascular
      injury, especially with malpositioned or deeply placed implants. METHODS: We
      present a case of proximal median nerve injury leading to severe neuropathy after
      attempted removal of a subdermal implantable contraceptive requiring neurolysis
      and tendon transfers. RESULTS: At 6 months post surgery, the patient regained
      flexion of the index interphalangeal joints and protective sensation in the thumb
      and index fingers. CONCLUSIONS: Subdermal implant retrieval can lead to nerve
      injury, despite the relative simplicity of the procedure. If difficulty is
      encountered, imaging or open retrieval should be considered. Improvement in
      function can be gained through operative interventions including neurolysis and
      tendon transfers in the setting of severe neuropathy.

PMID- 29185831
TI  - Series: Practical guidance to qualitative research. Part 1: Introduction.
AB  - In the course of our supervisory work over the years, we have noticed that
      qualitative research tends to evoke a lot of questions and worries, so-called
      Frequently Asked Questions. This journal series of four articles intends to
      provide novice researchers with practical guidance for conducting high-quality
      qualitative research in primary care. By 'novice' we mean Master's students and
      junior researchers, as well as experienced quantitative researchers who are
      engaging in qualitative research for the first time. This series addresses their
      questions and provides researchers, readers, reviewers and editors with
      references to criteria and tools for judging the quality of papers reporting on
      qualitative research. This first article describes the key features of
      qualitative research, provides publications for further learning and reading, and
      gives an outline of the series.

PMID- 29185832
TI  - Regulation of Reactionary Dentine Formation.
AB  - During the treatment of dental caries that has not penetrated the tooth pulp,
      maintenance of as much unaffected dentine as possible is a major goal during the
      physical removal of decayed mineral. Damage to dentine leads to release of
      fossilized factors (transforming growth factor-beta [TGF-beta] and bone
      morphogenic protein [BMP]) in the dentine that are believed to stimulate
      odontoblasts to secrete new "tertiary" dentine (reactionary dentine). This is
      formed on the pulpal surface of existing dentine and rethickens the dentine. We
      have previously shown that activation of Wnt/beta-catenin signaling is pivotal
      for tooth repair in exposed pulp injury, and the pathway can be activated by
      small-molecule GSK-3 antagonists, resulting in enhanced reparative dentine
      formation. Here, we use a nonexposed pulp injury model to investigate the
      mechanisms of reactionary dentine formation in vivo, using small molecules to
      modulate the Wnt/beta-catenin, TGF-beta, and BMP pathways. We found that a local
      increase of Wnt activation at the injury site enhances reactionary dentine
      secretion. In addition, inhibition of TGF-beta, BMP, or Wnt pathways does not
      impede reactionary dentine formation, although inhibition of TGF-beta and/or BMP
      signaling does result in more disorganized, nontubular reactionary dentine. This
      suggests that Wnt/beta-catenin signaling plays no major role in the formation of
      reactionary dentine, but in common with reparative dentine formation, exogenous
      elevation of Wnt/beta-catenin signaling can enhance tertiary dentine formation.
      Release of latent TGF-beta or BMPs from dentine is not required for the
      deposition of mineral to form reactionary dentine but does play a role in its
      organization.

PMID- 29185833
TI  - Disruption of Hif-1alpha enhances cytotoxic effects of metformin in murine
      squamous cell carcinoma.
AB  - PURPOSE: In the present study, we investigated whether the disruption of the Hif
      1alpha gene affects the sensitivity of SCC VII cells to metformin and also if
      metformin functions as a radiosensitizer using murine squamous cell carcinoma
      (SCC VII) cells. MATERIALS AND METHODS: Cultured SCC VII and SCC VII Hif-1alpha
      deficient cells were incubated with metformin under glucose-free and/or hypoxia
      mimetic conditions and cell viabilities were measured. Tumor-bearing mice were
      continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating
      cells. Tumor-bearing mice were then subjected to gamma-ray irradiation after the
      metformin treatment. Immediately after irradiation, cells were isolated from some
      tumors and incubated with a cytokinesis blocker. The responses of quiescent and
      total (= proliferating + quiescent) cell populations were assessed based on the
      frequency of micronuclei using immunofluorescence staining for BrdU. RESULTS: The
      disruption of Hif-1alpha increased the sensitivity of SCC VII cells to metformin
      in glucose-free medium. Metformin-induced decreases in the percentage of dead
      cells in the presence of CoCl2 were partially reduced when Hif-1alpha was
      disrupted. In vivo, metformin increased the radiosensitivity of SCC VII Hif
      1alpha-deficient cells. CONCLUSION: The combination of disruption of Hif-1alpha
      and metformin effectively enhanced the radiosensitivity of SCC VII cells.

PMID- 29185834
TI  - Resveratrol ameliorates ionizing irradiation-induced long-term immunosuppression
      in mice.
AB  - PURPOSE: Ionizing radiation has been associated with adverse effects on the
      immune system. Currently, there are no effective treatment options to ameliorate
      these effects. The aim of the present study was to investigate the protective
      effects of resveratrol against radiation-induced long-term immunosuppression in
      mice. MATERIALS AND METHODS: Mice were exposed to total body irradiation and
      treated with resveratrol or vehicle. Several immune parameters were measured,
      including thymus and spleen weights, T-lymphocyte and B-lymphocyte count in
      peripheral blood, concanavalin A and lipopolysaccharide induced lymphocyte
      proliferation. To explore the mechanism, we investigated intracellular ROS level
      of lymphocytes and mice plasma cytokine levels. RESULTS: Treatment with
      resveratrol ameliorated TBI-induced atrophy of the thymus and spleen, reduction
      of lymphocyte count and decline of lymphocyte proliferation. TBI exhibited
      significantly reduced level of IL-2, IL-4, IL-7 and IFN-gamma compared with the
      control mice and treatment with resveratrol attenuated the reduction. CONCLUSION:
      The results of the present study suggest that treatment with resveratrol could
      ameliorate irradiation induced long-term immune malfunction at least partly via
      modulation of plasma cytokine.

PMID- 29185835
TI  - Biometric Differences between Unilateral Chronic Primary Angle Closure Glaucoma
      and Fellow Non-Glaucomatous Eyes.
AB  - PURPOSE: To compare biometric differences between eyes with unilateral chronic
      primary angle-closure glaucoma (PACG) and fellow non-glaucomatous eyes in the
      same patient. METHODS: Clinical data and imaging records of 17 patients with
      unilateral PACG were retrospectively reviewed. The fellow eyes with primary angle
      closure (PAC) or primary angle-closure suspected (PACS) were grouped in Group 1.
      The PACG eyes were set as Group 2. The biometric parameters of both eyes were
      measured by IOL-Master, anterior segment optical coherence tomography (AS-OCT),
      and swept source OCT. RESULTS: The iris area in Group 1 was significantly thicker
      than that in Group 2 (1.590 +/- 0.267 versus 1.365 +/- 0.352, P = 0.016).
      Choroidal thickness in the macular region was thicker in Group 1 than in Group 2,
      with statistical significance at inner temporal grid (282.7 +/- 121.1 versus
      191.6 +/- 90.3, P = 0.036), central field (297.4 +/- 130.6 versus 200.1 +/- 96.3,
      P = 0.029), inner nasal grid (283.1 +/- 128.3 versus 194.8 +/- 91.8, P = 0.040),
      and average value (265.3 +/- 105.6 versus 191.1 +/- 87.0, P = 0.049). Group 1
      also had thicker peripapillary choroidal thickness at 1 o'clock (141.4 +/- 68.4
      versus 101.8 +/- 39.0, P = 0.025) and 12 o'clock (141.5 +/- 82.3 versus 104.5 +/-
      44.6, P = 0.037) compared to Group 2. The multivariate logistic regression
      analyses showed that only intraocular pressure was independently associated with
      PACG and explained 58.3% variance of PACG. CONCLUSIONS: In unilateral PACG, there
      was significant inter-eye difference in anterior and posterior segment
      parameters. Longitudinal comparisons are required to further understand the
      differences in pathology of angle closures.

PMID- 29185837
TI  - Effects of Negative Affect, Urge to Smoke, and Working Memory Performance (n
      back) on Nicotine Dependence.
AB  - BACKGROUND: Three key domains including negative emotionality, incentive
      salience, and executive function form the core functional elements of addictive
      behaviors. Variables related to these broader domains have been studied
      extensively in relation to one another; however, no studies to date, have
      examined models including variables from all three domains, in relation to
      nicotine dependence. METHOD: Smokers (N = 117), 65.8% female, 78% white, mean age
      of 44.4 (SD = 10.8), enrolled in a smoking cessation program completed measures
      of negative affect (a component of negative emotionality), urge to smoke
      (incentive salience), and working memory (WM; a core executive function), during
      a baseline assessment period prior to initiating treatment. RESULTS: Negative
      affect was associated with greater urge to smoke, and this elevated urge to smoke
      was associated with higher levels of nicotine dependence. Further, a significant
      moderated mediation indicated that WM moderated the relationship between
      increased urge to smoke and nicotine dependence. For those with low to average
      WM, urge to smoke was significantly related to nicotine dependence; however, for
      those with higher WM (+1 SD), urge to smoke stemming from negative affect was not
      associated with nicotine dependence. CONCLUSIONS: To our knowledge, this is the
      first reported relationship between negative affect, urge to smoke, WM, and
      nicotine dependence. Although preliminary, results indicate that WM may moderate
      the relationship between urge to smoke associated with negative affect and
      nicotine dependence. Treatments targeting WM may be particularly useful for
      individuals with average to low WM who experience urge to smoke related to
      negative affect.

PMID- 29185838
TI  - Cataract Surgery Complications in Uveitis Patients: A Review Article.
AB  - Uveitis is a leading causes of blindness worldwide, and the development of
      cataracts is common due to both the presence of intraocular inflammation and the
      most commonly employed treatment with corticosteroids. The management of these
      cataracts can be very challenging and often requires additional procedures that
      can compromise surgical results. The underlying disease affects a relatively
      young population at higher risk of complications. Preoperative control of
      inflammation/quiescent disease for at least three months is generally accepted as
      the minimum amount of time prior to surgical intervention. Phacoemulsification
      with intraocular lens is the preferred method for surgery, with some studies
      showing improvement in visual acuity in over 90% of patients. The most common
      postoperative complications include macular edema, posterior capsule
      opacification, recurrent or persistent inflammation, glaucoma, epiretinal
      membrane and IOL deposits, or dislocation. Despite the potential complications,
      cataract surgery in uveitis patients is considered a safe and successful
      procedure.

PMID- 29185836
TI  - Exome-chip meta-analysis identifies association between variation in ANKRD26 and
      platelet aggregation.
AB  - Previous genome-wide association studies (GWAS) have identified several variants
      associated with platelet function phenotypes; however, the proportion of variance
      explained by the identified variants is mostly small. Rare coding variants,
      particularly those with high potential for impact on protein structure/function,
      may have substantial impact on phenotype but are difficult to detect by GWAS. The
      main purpose of this study was to identify low frequency or rare variants
      associated with platelet function using genotype data from the Illumina
      HumanExome Bead Chip. Three family-based cohorts of European ancestry, including
      ~4,000 total subjects, comprised the discovery cohort and two independent
      cohorts, one of European and one of African American ancestry, were used for
      replication. Optical aggregometry in platelet-rich plasma was performed in all
      the discovery cohorts in response to adenosine diphosphate (ADP), epinephrine,
      and collagen. Meta-analyses were performed using both gene-based and single
      nucleotide variant association methods. The gene-based meta-analysis identified a
      significant association (P = 7.13 * 10-7) between rare genetic variants in
      ANKRD26 and ADP-induced platelet aggregation. One of the ANKRD26 SNVs -
      rs191015656, encoding a threonine to isoleucine substitution predicted to alter
      protein structure/function, was replicated in Europeans. Aggregation increases of
      ~20-50% were observed in heterozygotes in all cohorts. Novel genetic signals in
      ABCG1 and HCP5 were also associated with platelet aggregation to ADP in meta
      analyses, although only results for HCP5 could be replicated. The SNV in HCP5
      intersects epigenetic signatures in CD41+ megakaryocytes suggesting a new
      functional role in platelet biology for HCP5. This is the first study to use gene
      based association methods from SNV array genotypes to identify rare variants
      related to platelet function. The molecular mechanisms and pathophysiological
      relevance for the identified genetic associations requires further study.

PMID- 29185839
TI  - Therapeutic Efficacy of Conbercept for Inflammatory Choroidal Neovascularization.

PMID- 29185840
TI  - Single-Dose Levonorgestrel Emergency Contraception and Silent Barriers to Its
      Access: Is It Really Just One Step?
AB  - BACKGROUND: Single-dose levonorgestrel has been legally available over the
      counter in the United States without age restriction since 2013. The objective of
      this study was to discover if there are barriers to access and to determine if
      such barriers vary based on the gender of the person making the purchase.
      MATERIALS AND METHODS: A male and female caller contacted 146 Richmond, Virginia
      pharmacies listed on the Plan B One Step(r) website. Ultimately, these callers
      interviewed 90 pharmacies via phone and used a rehearsed standardized script to
      ask eight questions regarding emergency contraception (EC) in relation to
      availability, age restrictions, parental consent, counseling requirements, and a
      male's ability to purchase the product. The statistical data were analyzed using
      Fisher's exact test. RESULTS: Pharmacy employees provided incorrect information
      to both men and women regarding age restrictions for purchasing Plan B One Step
      51% of the time. However, only seven of the pharmacy employees counseled that
      males were unable to purchase the medication. Both callers received correct
      information regarding parental consent and in-store counseling at the time of
      purchase. Pharmacy technicians provided the majority of information, and the male
      caller was more likely to be transferred to another person when requesting the
      medication (9 vs. 0 transfers for the male and female callers, respectively).
      CONCLUSION: Given the inconsistent data provided to the public regarding the
      purchase of EC, clinicians are obligated to convey accurate up-to-date
      information to patients about emergency contraceptive products as part of their
      counseling and should not assume that consumers receive accurate information when
      inquiring about over-the-counter EC.

PMID- 29185841
TI  - Inhibitory Effect of Amitriptyline on the Impulse Activity of Cold Thermoreceptor
      Terminals of Intact and Tear-Deficient Guinea Pig Corneas.
AB  - PURPOSE: Chronic dryness of the ocular surface evokes sensitization of corneal
      cold-sensitive neurons through an increase of sodium currents and a decrease of
      potassium currents, leading to the unpleasant dryness and pain sensations typical
      of dry eye disease. Here, we explored the effects of amitriptyline, a voltage
      gated Na+ channel blocker used for the treatment of depression and chronic pain,
      on nerve terminal impulse (NTI) activity of cold-sensitive nerve terminals
      recorded in intact and tear-deficient guinea pig corneas. METHODS: Main lachrymal
      gland was surgically removed in anesthetized guinea pigs to induce chronic tear
      deficiency. Four to 6 weeks afterward, animals were sacrificed and both corneas
      placed in a perfusion chamber superfused at 34 degrees C. Thermal stimuli were
      induced by changing the solution temperature from 34 degrees C to 20 degrees C
      (cooling ramp) and from 34 degrees C to 50 degrees C (heating ramp). Spontaneous
      and stimulus-evoked NTIs of cold-sensitive nerve terminals were recorded before,
      during, and after perfusion with solutions containing amitriptyline at different
      concentrations (3-30 MUM). RESULTS: Perfusion with amitriptyline inhibited
      irreversibly and in a concentration-dependent manner the spontaneous NTI activity
      of cold thermoreceptors of intact corneas. This effect was less evident in tear
      deficient corneas. In addition, amitriptyline (10 MUM) attenuated the maximal
      response to cooling ramps without changing cold threshold in intact but not in
      tear-deficient corneas. Only cold thermoreceptors with low cooling threshold
      values were sensitive to amitriptyline. CONCLUSION: Amitriptyline effectively
      reduces the activity of cold thermoreceptors, although its efficacy is different
      in intact and tear-deficient corneas, which might be due to the changes induced
      by ocular dryness in the expression of the various voltage-gated Na+ channels
      responsible of the action potential generation and propagation.

PMID- 29185842
TI  - Characterizing a Hidden Group of At-Risk Drinkers: Epidemiological Profiles of
      Alcohol-Use Disorder Diagnostic Orphans.
AB  - BACKGROUND: Drinkers who report some symptoms of alcohol-use disorder (AUD) but
      fail to meet full criteria are "diagnostic orphans." To improve risk-reduction
      efforts, we sought to develop better epidemiologic profiles of this
      underrecognized subgroup. METHODS: This study estimated the population prevalence
      and described AUD symptoms of diagnostic orphans using the 2012-2013 National
      Epidemiological Survey of Alcohol and Related Conditions-III. Multivariate
      logistic regression was used to model odds of being a diagnostic orphan or
      meeting mild, moderate, and severe AUD criteria versus no AUD symptoms. Models
      were adjusted for the complex survey design using sampling weights and survey
      procedures (e.g., proc surveylogistic). RESULTS: Among drinkers, 14% of men and
      11% of women were classified as diagnostic orphans. The most common symptoms were
      drinking more or for longer periods than intended, wanting or trying
      unsuccessfully to quit or cut back, and drinking in ways that increased risk of
      injury. We noted broad similarities between diagnostic orphans and mild/moderate
      AUD groups. There were no differences in odds of diagnostic orphans status by
      race/ethnicity; however, female gender was associated with lower odds of
      diagnostic orphan status and all levels of AUD. Individual history of AUD, family
      history of problem drinking, concurrent smoking, and concurrent marijuana use
      were associated with greater odds of problem drinking, with stronger associations
      as AUD severity increased. CONCLUSIONS: Diagnostic orphans remain a sizeable and
      overlooked population of problem drinkers. Clarifying the array of symptoms and
      cooccurring disorders can improve screening and facilitate alcohol risk-reduction
      intervention efforts.

PMID- 29185843
TI  - Morphological and chromosomal abnormalities in gamma radiation-induced
      mutagenized faba bean genotypes.
AB  - PURPOSE: This study was conducted to evaluate and compare the influence of gamma
      radiations on morphological and chromosomal abnormalities in twenty mutagenized
      faba bean populations, representing first and second generations (M1 and M2) of
      five faba bean genotypes. MATERIALS AND METHODS: Five faba bean genotypes were
      exposed at two doses of gamma radiations (25 and 50 Gy). For determining the
      types of chromosomal aberrations caused by the gamma radiation, mitotic and
      meiotic cells were isolated from root tips and pollen mother cells, respectively.
      RESULTS: The M1 generations of the five genotypes varied for sensitivity to gamma
      radiations, for seedling emergence. The genotype Skah 2 was more sensitive than
      other genotypes, the order of sensitivity of other genotypes was Misr 3 > ILB
      4347 > Hassawi 2 > Hassawi 3. However, seedling emergence of the M2 generations
      was not as much reduced as that of the M1 generations. Ten different chlorophyll
      deficient mutants were identified among the M2 generations. Gamma radiations also
      caused the development of abnormal leaflets, flowers and pollen grains. The most
      common types of chromosome aberrations in the mitotic cells were stickiness,
      laggard, and chromosome breaks, whereas the most common types in the meiotic
      cells were stickiness and disturbed polarity. CONCLUSION: The gamma radiation
      decreased the seedling emergence and induced a wide range of morphological and
      chromosomal abnormalities in faba bean.

PMID- 29185844
TI  - Postoperative Complications of Scleral Buckling.
AB  - Scleral buckling has an important role in the repair of certain categories of
      rhegmatogenous retinal detachments. These include detachments in young phakic
      patients, detachments associated with dialysis, and also in conjuction with
      vitrectomy in patients who have sustained trauma or have developed proliferative
      vitreoretinopathy. However, it can be associated with significant postoperative
      complications. The most important ones are refractive change, intrusion or
      extrusion, infection, globe ischemia, and choroidal detachments, amongst others.
      Careful planning, appropriate patient selection, and good intraoperative
      technique can reduce the rate of these complications.

PMID- 29185845
TI  - A Qualitative Study on the Effects of Psychoactive Substance use upon Artistic
      Creativity.
AB  - BACKGROUND: Psychoactive substance use has often been claimed to help generate
      and facilitate the artistic creative process. AIMS: This study explored the role
      of artists' substance use in their creative processes and their efforts to
      balance between enhancement and relaxation. METHODS: Semistructured interviews
      concerning the artistic creative process and the role of psychoactive substance
      use were recorded with 72 artists and analyzed using content analysis. The
      participants were classified according to their substance use in three groups
      (Cannabis Group, Alcohol Group, and Control Group). RESULTS: Results show that
      both alcohol and cannabis were used to facilitate creativity and the emotional
      states that are necessary for the artistic creative process. Participants in the
      Control group reported that listening to music might function as a mind-altering
      tool. It was also found that for some artists, substance use is not only
      characteristic to creation, but it is also part of their everyday lives.
      CONCLUSION: Artists are aware of the balancing phenomenon during the artistic
      creative process. Whether psychoactive substance(s) or other environmental
      stimuli (such as music) are used to reach the required effect appears to depend
      upon the individual.

PMID- 29185846
TI  - Adverse Childhood Experiences (ACEs) and Alcohol Abuse among South Carolina
      Adults.
AB  - BACKGROUND: Adverse childhood experiences (ACEs) have been associated with
      negative adult health outcomes, including alcohol misuse. The impact of ACEs on
      alcohol use may vary by gender, with ACEs impacting women more than men in coping
      with adulthood stressors. OBJECTIVES: The objective of this study is to examine
      the gender-specific relationships between ACEs and self-reported binge drinking
      and heavy drinking in adulthood among South Carolina residents. METHODS: This
      study analyzed a sample of 8492 respondents who completed the 2014 or 2015 South
      Carolina Behavioral Risk Factor Surveillance System (BRFSS) survey. Logistic
      regression was used to examine the impact of types and the number of ACEs on
      binge drinking and heaving drinking in adulthood. RESULTS: Thirty-seven percent
      of men and 22.8% of women survey respondents reported binge drinking and 12.2% of
      men and 4.1% of women reported heavy drinking. Almost all categories of ACE were
      associated with increased odds of reporting binge and heavy drinking; household
      mental illness had the greatest odds for men (aOR 1.31, 95% CI 1.30-1.33) and
      emotional abuse had the greatest odds for women (aOR 1.42, 95% CI 1.40-1.43). Men
      and women with four or more ACEs had greater odds of reporting binge and heavy
      drinking compared to their counterparts. Conclusions/Importance: Given the
      potential for negative outcomes associated with alcohol misuse and transmission
      of risky alcohol-related behaviors from parent to child, strategies that utilize
      a multigenerational approach could have a large impact on population health.

PMID- 29185847
TI  - Screening for Psychological Conditions in Infertile Women: Provider Perspectives.
AB  - PURPOSE: To determine if reproductive specialists are screening new patients for
      depression or anxiety, explore possible reasons why providers are not screening,
      and assess physician's views about the impact of mental health disorders on
      fertility. MATERIALS AND METHODS: Cross-sectional exploratory study in which 86
      practicing reproductive physicians filled out a 20-question survey regarding
      mental health screening and perception of psychological disorders on
      reproduction. RESULTS: The majority of infertility providers believe
      psychological conditions negatively impact pregnancy success (75%); however, most
      providers are not formally screening patients for depression or anxiety (28%).
      Providers who did not screen for depression were more likely to be uncomfortable
      assessing patients for mental health disorders and to work in a private practice
      setting. CONCLUSIONS: This study finds that most infertility specialist
      respondents believe that mental health conditions negatively impact reproductive
      outcomes; however, few of these providers are screening for psychological
      disorders in infertile women. Reasons why providers are not screening infertility
      patients for psychological disorders include lack of time and unfamiliarity with
      recommendations for treatment of mental health conditions. Implementing a rapid
      screen for anxiety and depression and providing easily assessable succinct
      educational updates to fertility providers on current treatment options for
      mental health disorders may allow affected patients to be treated sooner, and
      ultimately, may improve fertility outcomes.

PMID- 29185849
TI  - RAS ubiquitylation modulates effector interactions.
AB  - RAS proteins function as molecular switches that regulate cellular growth by
      cycling between active GTP- and inactive GDP bound states. While RAS activity is
      modulated by factors (guanine nucleotide exchange and GTPase activating proteins)
      that control levels of active Ras-GTP, RAS proteins also undergo a number of post
      translational modifications that regulate their function. One such modification
      is ubiquitylation. Monoubiquitylation of KRAS at lysine 147 (mUbRAS) enhances Ras
      activation and promotes signaling through the RAF and Phosphoinositide 3-Kinase
      (PI3K) signaling pathways. We have previously shown that mUbRAS leads to
      activation of RAS through a defect in GTPase activating protein (GAP) mediated
      downregulation, similar to the action of most oncogenic mutations. Consistent
      with these findings, we now show that mUbRASimpairsRAS binding to the p120 GAP
      catalytic domain. Mutations in activated G12V RAS that prevent ubiquitylaton at
      147 show a decrease in tumorigenesis, suggesting that in addition to activating
      KRAS, monoubiquitylation at this site may promote downstream signaling and
      transformation. To investigate whether mUbRAS alters RAS effector interactions,
      we chemically ubiquitylated KRAS at residue 147 and characterized binding of
      mUbRAS to RAS binding domains (RBDs) from three distinct downstream effectors
      that play key roles in RAS-mediated transformation. Results from these studies
      show a decrease in binding of mUbRAS (7-10-fold) relative to the CRAF RAS Binding
      Domain (RBD), the catalytic subunit of Phosphoinositide 3-Kinase catalytic gamma
      (PI3Kcgamma) and RALGDS RBD. Intriguingly, we find that mUbRAS shows greatly
      enhanced (> 40-fold) binding to the CRAF RBD when bound to GDP. These findings,
      taken together, suggest that mUbRASmay promoteactivation of RAS through a GAP
      defect, and facilitate RAF association and MAPK signaling in a nucleotide
      independent manner.

PMID- 29185850
TI  - Polymorphic Microsatellite Markers for Solen grandis and Their Cross-Species
      Amplification in Three Other Species.
AB  - The grand jackknife clam Solen grandis is a commercially important mollusk
      species, but has been suffering from severe population decline due to over
      exploitation and habitat destruction in China. To promote a conservation program
      for this species, it is necessary to evaluate its genetic diversity and
      population genetics. In this study, 10 novel polymorphic microsatellite makers
      were developed and characterized from the S. grandis through high throughput
      sequencing. The number of alleles at each locus ranged from 10 to 34 with an
      average of 20.8 alleles per locus. The observed and expected heterozygosities
      varied from 0.433 to 1.000 and from 0.696 to 0.976, with an average of 0.793 and
      0.884, respectively. The polymorphism information content (PIC) value ranged from
      0.633 (Sg43838) to 0.958 (Sg3754), with an average of 0.858. The cross-species
      amplification transferability of 10 loci to three closely related species ranged
      from 4.17 to 62.5%. These microsatellite loci will be useful for further
      investigation of population structure and conversation genetics of this species.

PMID- 29185848
TI  - Monoclonal antibodies targeting the disintegrin-like domain of ADAMDEC1 modulates
      the proteolytic activity and enables quantification of ADAMDEC1 protein in human
      plasma.
AB  - Decysin-1 (ADAMDEC1) is an orphan ADAM-like metalloprotease with unknown
      biological function and a short domain structure. ADAMDEC1 mRNA has previously
      been demonstrated primarily in macrophages and mature dendritic cells. Here, we
      generated monoclonal antibodies (mAbs) against the mature ADAMDEC1 protein, as
      well as mAbs specific for the ADAMDEC1 pro-form, enabling further investigations
      of the metalloprotease. The generated mAbs bind ADAMDEC1 with varying affinity
      and represent at least six different epitope bins. Binding of mAbs to one epitope
      bin in the C-terminal disintegrin-like domain efficiently reduces the proteolytic
      activity of ADAMDEC1. A unique mAb, also recognizing the disintegrin-like domain,
      stimulates the caseinolytic activity of ADAMDEC1 while having no significant
      effect on the proteolysis of carboxymethylated transferrin. Using two different
      mAbs binding the disintegrin-like domain, we developed a robust, quantitative
      sandwich ELISA and demonstrate secretion of mature ADAMDEC1 protein by primary
      human macrophages. Surprisingly, we also found ADAMDEC1 present in human plasma
      with an approximate concentration of 0.5 nM. The presence of ADAMDEC1 both in
      human plasma and in macrophage cell culture supernatant were biochemically
      validated using immunoprecipitation and Western blot analysis demonstrating that
      ADAMDEC1 is secreted in a mature form.

PMID- 29185851
TI  - The Preference for Social Affiliation Renders Fish Willing to Accept Lower O2
      Levels.
AB  - Animals are bombarded with information about their environment and must select
      and interpret the relevant cues to make behavioral adjustments critical to
      survival. How animals integrate and balance the many signals they receive about
      their environment is rarely assessed. We investigated how signals from the social
      and physical environment interact to influence environmental preferences in the
      endemic Tanganyikan cichlid Neolamprologus pulcher. Specifically, we explored how
      fish respond to the physiological challenge of declining O2 levels in light of
      embedded social preferences using a modified shuttle box apparatus to test O2
      preferences. In the presence of a conspecific, the average (preferred) partial
      pressure of oxygen (Po2) and minimum Po2 experienced were significantly lower
      ([Formula: see text] and [Formula: see text] kPa, respectively) than in trials
      without a conspecific ([Formula: see text] and [Formula: see text] kPa,
      respectively). Fish with conspecifics also spent more time in the low Po2 zone of
      the shuttle box and moved between the high and low Po2 zones less frequently.
      Hence, O2 preferences were modified, and fish willingly remained in an area of
      continuously declining O2 availability to associate with a conspecific. The O2
      preferences of an individual during social trials correlated with its excess
      postexercise O2 consumption following an exhaustive chase but not with its
      aerobic scope, routine O2 consumption rate, or body mass. These results suggest
      that some aspects of respiratory and metabolic physiology (such as the propensity
      to use anaerobic metabolism) but not others (such as O2 transport capacity)
      underpin some variation in social behavior under environmental stress.

PMID- 29185852
TI  - Lethal Fascioliasis in Capybaras ( Hydrochoerus hydrochaeris) in Brazil.
AB  - The liver fluke Fasciola hepatica (Trematoda: Fasciolidae) causes fascioliasis,
      which affects mostly domestic ruminants and humans worldwide. This parasite has
      an Old World origin and was introduced into the New World by European colonizers.
      Capybara ( Hydrochoerus hydrochaeris) is the largest living rodent species, with
      adults weighing over 60 kg. We report a fascioliasis outbreak caused by F.
      hepatica that reduced a capybara group from 21 to 2 animals within a 9-mo period.
      Animal infection and associated lesions were confirmed by postmortem examinations
      that revealed extensive liver damage associated with the presence of large number
      of adult and immature forms of F. hepatica. Both macroscopic and microscopic
      alterations in the liver were compatible with acute fascioliasis, which is
      characterized by a large parasite burden in the liver. Taxonomic identification
      of flukes collected from capybara livers were confirmed by molecular methods,
      which generated a mitochondrial NADH dehydrogenase I (NDI) gene partial sequence
      that was 100% identical to a F. hepatica NDI sequence from the United Kingdom.
      This is the first report of deleterious effects caused by F. hepatica in
      capybaras, highlighting the potential harm caused by this exotic parasite in the
      capybara.

PMID- 29185853
TI  - Synthesis, characterization and biological evaluation of C5'-N
      cyclopropylcarboxamido-C6-amino-C2-alkynylated purine nucleoside analogues.
AB  - In an effort to develop potent antibacterial and anticancer agents, a series of
      C5'-N-cyclopropylcarboxamido-C6-amino-C2-alkynylated purine nucleoside analogues
      11a-g were synthesized through a Sonogashira cross-coupling reaction. The nine
      step synthesis is easy to perform, and employs commercially available reagents. 2
      Iodo-5'-N-cyclopropylcarboxamidoadenosine (9) was used as the starting
      intermediate for the synthesis of title derivatives 11a-g. Synthetic
      intermediates (2-9) and final products (11a-g) were appropriately characterized
      by IR, 1H NMR, 13C NMR and mass spectroscopy. The synthesized purine nucleoside
      analogues (11a-g) were evaluated for their in vitro antibacterial activity
      against two gram-positive and two gram-negative bacteria. They were then tested
      for cytotoxicity against MDA-MB-231 and Caco-2 cancer cell lines to determine
      their anti-cancer activity. Among the tested compounds, compounds 11c and 11g
      showed most potent antibacterial activity against S.aureus and P.aeruginosa
      bacterial strains. Compounds 11b and 11e displayed considerable IC50s of 7.9 and
      6.8 ug/mL, respectively, vs MDA-MB-231 cell lines of 7.5 and 8.3 ug/mL,
      respectively, against the Caco-2 cell lines.

PMID- 29185854
TI  - Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in Cystic
      Fibrosis Patients from Argentina.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) colonization in cystic
      fibrosis (CF) patients is an increasing problem in many countries. In our
      Respiratory Center at the Hospital de Ninos "Dr. Ricardo Gutierrez", Buenos
      Aires, Argentina, the prevalence has climbed from 23% in 1995 up to 32% in 2011.
      Our objective was to analyze the diversity of MRSA isolates recovered from
      respiratory samples of CF patients attending our center, characterizing their
      phenotypes and clonal distribution. Therefore, a prospective study was conducted
      on all CF patients attending the pediatric Respiratory Center between June 2012
      and May 2013 to collect MRSA isolates. Antibiotic susceptibility testing,
      multilocus sequence typing, pulsed-field gel electrophoresis, spa typing, and agr
      genotyping were performed on collected isolates. The prevalence of MRSA during
      this period was 34.2%, and 71.9% of the patients were infected with isolates that
      carried SCCmec IV. High resistance rates were detected for gentamicin,
      erythromycin, clindamycin, ciprofloxacin, and rifampicin. Strains related to the
      community-associated MRSA clones, ST5-IV and ST30-IV, were the most frequently
      recovered. Remarkably, even though most of the isolates were related to these
      clones, the rate of multi-resistance shown in CF patients was higher than that
      reported for the same lineages recovered from other infections in our country.

PMID- 29185855
TI  - Production of a germline-humanized cetuximab scFv and evaluation of its activity
      in recognizing EGFR- overexpressing cancer cells.
AB  - The aim of this study was to produce a humanized single chain antibody (scFv) as
      a potential improved product design to target EGFR (Epidermal Growth Factor
      Receptor) overexpressing cancer cells. To this end, CDR loops of cetuximab (an
      FDA-approved anti-EGFR antibody) were grafted on framework regions derived from
      type 3 (VH3 and VL3 kappa) human germline sequences to obtain recombinant VH and
      VL domainslinked together with a flexible linker [(Gly4Ser)3] to form a scFv.
      Codon optimized synthetic gene encoding the scFv (with NH2-VH-linker-VL-COOH
      orientation) was expressed in E. coli OrigamiTM 2(DE3) cells and the resultant
      scFv purified by using Ni-NTA affinity chromatography. The scFv, called cet.Hum
      scFv, was evaluated in ELISA and immunoblot to determine whether it can recognize
      EGFR. The scFv was able to recognize EGFR over-expressing cancer cells (A-431)
      but failed to detect cancer cells with low levels of EGFR (MCF-7 cells). Although
      the affinity of the scFv forA-431 cells was 9 fold lower than that of cetuximab,
      it was strong enough to recognize these cells. Considering its ability to bind
      EGFR molecules, the scFv may exhibit a potential application for the detection of
      EGFR-overexpressing cancer cells.

PMID- 29185856
TI  - Anticancer, antibacterial and antifungal activity of new ni (ii) and cu (ii)
      complexes of imidazole-phenanthroline derivatives.
AB  - Two new nickel(II) and copper(II) complexes of 2-(Furan-2-yl)-1H-Imidazo[4,5
      f][1,10]Phenanthroline (FIP) and 2-(thiophen-2-yl)-1H-imidazo[4,5
      f][1,10]phenanthroline (TIP), imidazophen derivatives were synthesized. The
      structures of the compounds were determined by UV-visible and FT-IR spectroscopic
      methods and elemental analysis. The biological activities of Ni and Cu complexes,
      as anticancer agents, were tested against chronic myelogenous leukemia cell line,
      K562, at micromolar concentration. The MTT studies showed Cc50 values are 21 and
      160 uM for Cu and Ni(II) complexes, respectively; suggesting that Ni (II) complex
      has Cc50 almost seven times of that obtained for cisplatin. Biological activity
      of the Ni(II) and Cu(II) complexes were also assayed against selective
      microorganisms by disc diffusion method. These results showed that the Cu(II)
      complex is antifungal agent but Ni(II) complex has antibacterial activity.

PMID- 29185857
TI  - Chasing Seasonal Influenza - The Need for a Universal Influenza Vaccine.

PMID- 29185858
TI  - Antimicrobial Resistance in Escherichia coli Isolated from Wild Animals in
      Poland.
AB  - Antimicrobial resistance was tested in Escherichia coli isolated from feces (n =
      660) of red deer, roe deer, fallow deer, European bison, and wild boar shot in
      regional forests in Poland during two winter hunting seasons. Indicator E. coli
      (n = 542) was resistant against 11 of 14 tested compounds, mostly
      sulfamethoxazole, streptomycin, ampicillin, trimethoprim, and tetracycline (1.3
      6.6% range). No significant differences were observed between boar and ruminant
      isolates. Most of deer and bison isolates showed no resistance. Selective
      screening of wildlife samples revealed 1.7% prevalence of cephalosporin-resistant
      E. coli found mostly in wild boars. They produced extended-spectrum beta
      lactamases (blaCTX-M-1, blaCTX-M-15) and plasmid-mediated AmpC-type
      cephalosporinase (blaCMY-2). The majority of the isolates originated from boars
      shot in a narrow time frame and space; therefore, common antimicrobial selection
      pressure in the environment was assumed. Three E. coli isolates carried plasmid
      mediated quinolone resistance genes (qnrS1/S3). No transferable colistin
      resistance mechanisms were found in two resistant E. coli. Transferability of
      resistance was proved in a single pAmpC-positive isolate carrying IncI1-alpha 95
      kb plasmid. No cephalosporin-resistant E. coli harbored pathogenicity markers;
      therefore, they might be considered a vector of resistance determinants, but not
      a pathogen themselves.

PMID- 29185859
TI  - Burden of Rifampicin- and Methicillin-Resistant Staphylococcus aureus in Italy.
AB  - Rifampicin is one of the major drugs used on its own and also in combination to
      treat numerous infections sustained by methicillin-resistant Staphylococcus
      aureus (MRSA). In Italy, rifampicin resistance (RIF-R) is increasing in multidrug
      resistant-MRSA isolates (16.4%), with respect to Europe (5.7%). In our study, the
      relationship between clones, rpoB mutations, and susceptibility profiles in 50
      RIF-R MRSA isolated from hospitalized patients was evaluated. Antimicrobial
      susceptibility testing was performed by the broth microdilution method. Isolates
      were typed by MLST/SCCmec/spa-typing. The rpoB gene was analyzed by PCR and
      sequence analysis. RIF-R isolates were 60% heterogeneous vancomycin-intermediate
      S. aureus (hVISA) and 22% daptomycin nonsusceptible and belonged to the major
      MRSA clones: ST228-SCCmec I (44%), ST8-SCCmec IV (18%), ST239-SCCmec III (16%),
      ST5-SCCmec II (14%), and ST22-SCCmec IVh (4%). Thirteen diverse RpoB amino acid
      substitutions were identified. Half of the strains harbored the H481N
      substitution, conferring low-level resistance. Different single mutations at the
      equivalent locus (H481D; H481Y) or in other loci, and multiple mutations
      conferred high-level resistance. In conclusion, this study investigated the
      nature of RIF-R in Italy among RIF-R-MRSA strains, finding a prevalence of ST228,
      strongly associated with reduced susceptibility to glycopeptides (hVISA). The
      spread of RIF-R strains in clinical settings represents a serious threat, due to
      their complex resistance nature even to new anti-Gram-positive drugs, making
      these infections particularly difficult to treat.

PMID- 29185860
TI  - High prevalence of mouse mammary tumor virus-like gene sequences in breast cancer
      samples of Iranian women.
AB  - Mouse mammary tumor virus (MMTV) is considered to be responsible for breast tumor
      development in mice. In several instances sequences homologous to the genome of
      this virus have been reported in human breast cancer samples. Here we aimed to
      evaluate MMTV involvement in human breast cancer development. DNA was extracted
      from 118 formalin fixed and paraffin embedded malignant (n = 59) and benign (n =
      59) breast lesions. Using two sets of outer and inner MMTV-like envelope specific
      primers, in a nested PCR setup, MMTV genome was detected in 19 samples out of 59
      (%32.2) cases of breast carcinomas, while in non-malignant breast tissue samples,
      only 3 samples out of 59 (%5) were positive. The difference was statistically
      highly significant (p < 0.001). Alignment of PCR amplified sequences with BR6, GR
      and C3H mouse mammary tumor virus strains emerged to be around 99% identical
      which is indicative of tumor tissue infection by an exogenous mouse MMTV genome.

PMID- 29185861
TI  - Of rings and spines: The multiple facets of Citron proteins in neural
      development.
AB  - The Citron protein was originally identified for its capability to specifically
      bind the active form of RhoA small GTPase, leading to the simplistic hypothesis
      that it may work as a RhoA downstream effector in actin remodeling. More than two
      decades later, a much more complex picture has emerged. In particular, it has
      become clear that in animals, and especially in mammals, the functions of the
      Citron gene (CIT) are intimately linked to many aspects of central nervous system
      (CNS) development and function, although the gene is broadly expressed. More
      specifically, CIT encodes two main isoforms, Citron-kinase (CIT-K) and Citron-N
      (CIT-N), characterized by complementary expression pattern and different
      functions. Moreover, in many of their activities, CIT proteins act more as
      upstream regulators than as downstream effectors of RhoA. Finally it has been
      found that, besides working through actin, CIT proteins have many crucial
      functional interactions with the microtubule cytoskeleton and may directly affect
      genome stability. In this review, we will summarize these advances and illustrate
      their actual or potential relevance for CNS diseases, including microcephaly and
      psychiatric disorders.

PMID- 29185862
TI  - The Effects of 2'-O-Methoxyethyl Oligonucleotides on Renal Function in Humans.
AB  - Systemically administered 2'-O-methoxyethyl (2'MOE) antisense oligonucleotides
      (ASOs) accumulate in the kidney and metabolites are cleared in urine. The effects
      of eleven 2'MOE ASOs on renal function were assessed in 2,435 patients from 32
      phase 2 and phase 3 trials. The principle analysis was on data from 28 randomized
      placebo-controlled trials. Mean levels of renal parameters remained within normal
      ranges over time across dose groups. Patient-level meta-analyses demonstrated a
      significant difference between placebo-treated and 2'MOE ASO-treated patients at
      doses >175 mg/week in the percentage and absolute change from baseline for serum
      creatinine and estimated glomerular filtration rate. However, these changes were
      not clinically significant or progressive. No dose-related effects were observed
      in the incidence of abnormal renal test results in the total population of
      patients, or subpopulation of diabetic patients or patients with renal
      dysfunction at baseline. The incidence of acute kidney injury [serum creatinine
      >=0.3 mg/dL (26.5 MUM) increases from baseline or >=1.5 * baseline] in 2'MOE ASO
      treated patients (2.4%) was not statistically different from placebo (1.7%, P =
      0.411). In conclusion, in this database, encompassing 32 clinical trials and 11
      different 2'MOE ASOs, we found no evidence of clinically significant renal
      dysfunction up to 52 weeks of randomized-controlled treatment.

PMID- 29185863
TI  - Comparison of the diastereoisomeric excess of uridine, inosine and adenosine
      cyanohydrins determined by HPLC-DAD and 1H NMR.
AB  - The separation of the diastereoisomers of the nucleoside derivatives of uridine,
      inosine and adenosine was performed by HPLC using chiral and no chiral columns,
      it was observed with the no chiral columns the resolution was good enough to
      determine diastereoisomeric excess. These methods were compared with 1H NMR, and
      no significant differences were observed between the three techniques.
      Diastereoisomeric uridine (3a), inosine (3b) and adenosine (4c) cyanohydrins were
      resolved by 1H nuclear magnetic resonance (1H NMR), chiral normal phase-high
      performance liquid chromatography-diode array detector (NP-HPLC-DAD) and reversed
      phase (RP-HPLC-DAD); these methods allowed the assesment of the percent
      diastereoisomeric excess (% de) of the nucleosidic cyanohydrins of 3a (4, 6 and
      4), 3b (10, 8 and 6) and 4c (4, 4 and 4). To the best of our knowledge, there are
      no reports using analytical techniques for the separation of the epimers of 3a,
      3b and 4c.

PMID- 29185864
TI  - Novel mutation in the human HPRT1 gene and the Lesch-Nyhan disease.
AB  - Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of
      purine metabolism in which the enzyme, hypoxanthine-guanine
      phosphoribosyltransferase (HGprt) is defective. The authors report a novel point
      mutation that led to HGprt-related neurological dysfunction (HND) in a family in
      which there was a missense mutation in exon 6 of the coding region of the HPRT1
      gene: g.34938G>T, c.403G>T, p.D135Y. Molecular diagnosis is consistent with the
      genetic heterogeneity of the HPRT1 gene responsible for HGprt deficiency. It
      allows fast, accurate carrier detection and genetic counseling.

PMID- 29185865
TI  - Statistical Methods for Conditional Survival Analysis.
AB  - We investigate the survival distribution of the patients who have survived over a
      certain time period. This is called a conditional survival distribution. In this
      paper, we show that one-sample estimation, two-sample comparison and regression
      analysis of conditional survival distributions can be conducted using the regular
      methods for unconditional survival distributions that are provided by the
      standard statistical software, such as SAS and SPSS. We conduct extensive
      simulations to evaluate the finite sample property of these conditional survival
      analysis methods. We illustrate these methods with real clinical data.

PMID- 29185866
TI  - Eye-Movement Evidence for Object-Based Attention in Chinese Reading.
AB  - Is attention allocated to only one word or to multiple words at any given time
      during reading? The experiments reported here addressed this question using a
      novel paradigm inspired by classic findings on object-based attention. In
      Experiment 1, participants ( N = 18) made lexical decisions about one of two
      spatially colocated Chinese words or nonwords. Our main finding was that only the
      attended word's frequency influenced response times and accuracy. In Experiment
      2, participants ( N = 30) read target words embedded in two spatially colocated
      Chinese sentences. Our key finding here was that only target-word frequencies
      influenced looking times and fixation positions. These results support the
      hypothesis that words are attended in a strictly serial (and perhaps object
      based) manner during reading. The theoretical implications of this conclusion are
      discussed in relation to models of eye-movement control during reading and the
      conceptualization of words as visual objects.

PMID- 29185867
TI  - Change of olfactory function as a marker of inflammatory activity and disability
      progression in MS.
AB  - BACKGROUND: Impaired olfactory threshold has been reported in early inflammatory
      phases of MS, while impaired odor identification was associated with more
      widespread disability. OBJECTIVE: To prospectively assess the development of
      olfactory function and its correlation with relapse and disability progression.
      METHODS: In this prospective, 3-year longitudinal study on 151 MS patients and 30
      healthy controls, three different qualities of olfactory function (threshold,
      discrimination, and identification) were quantified using the Sniffin' Sticks
      test. The influence of relapses and disability on olfactory function was analyzed
      at different time points and in a multivariate model. RESULTS: Discrimination and
      identification capability significantly worsened over 3 years, while threshold
      did not. Threshold was markedly impaired in patients with relapse activity within
      12 months, recovered in the absence of relapse, and was associated with a 2.5
      fold increased risk of relapse. Deterioration of discrimination and
      identification was irreversible and both strongly associated with and predictive
      of EDSS progression. CONCLUSION: Olfactory function changes over time in MS.
      Threshold impairment is transient and predicts inflammatory disease activity,
      while odor identification and discrimination are associated with disability
      progression. Olfactory dysfunction might be a useful and easily obtainable
      parameter to monitor patients with regard to inflammation and neurodegeneration
      in MS.

PMID- 29185868
TI  - Three case studies of nonparaneoplastic limbic encephalitis (NPLE) in young adult
      males: Onset, course, and recovery following rehabilitation services.
AB  - Limbic encephalitis (LE) is a rare neurological disorder characterized by
      inflammation of the brain caused by autoimmunity or infection. LE has been a
      difficult to define and diagnose disorder due to the insidious and nonspecific
      (e.g., irritability, low mood, short-term memory complaints) presentation of
      early symptoms, as well as inconsistent findings on neuroimaging, lumbar puncture
      serum analysis, and electroencephalogram. Seizures, memory problems, and
      psychiatric disturbance are among the earliest and most prominent clinical
      features. This manuscript describes three adolescent males who developed LE and
      became psychotic, needed inpatient care, were trialed on various psychotropic
      medications, and exhibited lingering cognitive and psychiatric issues, though
      generally had very positive recoveries and return to community activities. There
      was no history of psychiatric disturbance, developmental disorder, or learning
      difficulties in any of these three young men. Two of the three cases exhibited a
      long, insidious symptom onset. None of the adolescents benefitted from
      antipsychotic medications and did not begin to experience improvement and
      eventual recovery until intravenous immunoglobulin (IVIG) was added to their
      treatment regimen. Neuropsychological consultation and team education was helpful
      in each of these cases. Neuropsychological findings for each individual are
      presented.

PMID- 29185870
TI  - Retaliation or selfishness? An rTMS investigation of the role of the dorsolateral
      prefrontal cortex in prosocial motives.
AB  - Equity, fairness and cooperative behavior are crucial for everyday social
      interactions. Recent neuroimaging studies suggest that the dorsolateral
      prefrontal cortex (DLPFC) is involved in the evaluation of violations of fairness
      rules, though difficulties remain to determine its role in implementing
      retaliating or forgiving responses to unfairness. Accordingly, we applied
      repetitive transcranial magnetic stimulation (rTMS) to the left and right DLPFC
      and investigated the impact of the DLPFC on retaliation and selfishness using a
      sequential neuroeconomic task establishing a role reversal. That is, participants
      first played an Ultimatum Game (in the role of a recipient) against fair or
      unfair proposers, followed by a Dictator Game in the role of a proposer.
      Following inhibition of the right DLPFC, subjects showed an increased punishment
      rate regarding previously unfair opponents. Surprisingly, previously fair
      opponents were also treated less fairly after rTMS to the right DLPFC, but not
      after left or sham rTMS. Previous work suggests that the right DLPFC provides
      "top-down" cognitive control over prepotent emotional responses to unfairness.
      Our results indicate, however, that the right DLPFC may be involved in
      controlling selfish behavior and that its suppression leads to maximization of
      one's own benefit, regardless of another's fairness or unfairness in previous
      encounters.

PMID- 29185871
TI  - Psychometric and Faciometric Support for observable Facial Feminization in Gay
      Men.
AB  - Though male homosexuality appears to be evolutionarily paradoxical, phenotypic
      feminization has been offered as a route for three current models positing a
      genetic basis for male homosexuality. We tested whether facial feminization is
      observable in gay men in two studies. In Study 1, using two composite images of
      gay and of heterosexual men, naive participants (N = 308) rated the "gay" face
      more highly on stereotypically feminine traits and actual femininity and the
      "heterosexual" face more highly on stereotypically masculine traits and actual
      masculinity. In Study 2, faciometrics of 428 Internet images of gay (N = 219) and
      heterosexual men were analyzed along six sexually dimorphic ratios. The
      faciometrics of gay men were more feminine, both in gestalt terms and for five of
      the six individual traits. The studies offer objective support for a more
      feminized facial phenotype in gay males that is difficult to explain through
      cultural or behavioral cues.

PMID- 29185872
TI  - Committed, Unmarried Same-Sex Couples and their Social Networks in the United
      States: Relationships and Discursive Strategies.
AB  - This study examines two aspects of the experiences that committed, unmarried same
      sex couples have with social network members (friends and family members). The
      study examines how remaining unmarried affected the couples' relationships with
      social network members and the discursive strategies couples use when discussing
      their relationship with social network members. Twenty-seven committed, unmarried
      U.S. same-sex couples were interviewed. Couples described two challenges in their
      relationships with social network members as a result of not marrying: others
      perceived their commitment level as lessened because they did not marry, and
      others supported their relationship less because they did not marry. Couples used
      four discursive strategies to establish and maintain their family identity when
      interacting with social network members. Couples' relational experiences and
      discursive strategies were consistent with previous descriptions of discourse
      dependent families.

PMID- 29185869
TI  - Development and Validation of a Novel Integrated Clinical-Genomic Risk Group
      Classification for Localized Prostate Cancer.
AB  - Purpose It is clinically challenging to integrate genomic-classifier results that
      report a numeric risk of recurrence into treatment recommendations for localized
      prostate cancer, which are founded in the framework of risk groups. We aimed to
      develop a novel clinical-genomic risk grouping system that can readily be
      incorporated into treatment guidelines for localized prostate cancer. Materials
      and Methods Two multicenter cohorts (n = 991) were used for training and
      validation of the clinical-genomic risk groups, and two additional cohorts (n =
      5,937) were used for reclassification analyses. Competing risks analysis was used
      to estimate the risk of distant metastasis. Time-dependent c-indices were
      constructed to compare clinicopathologic risk models with the clinical-genomic
      risk groups. Results With a median follow-up of 8 years for patients in the
      training cohort, 10-year distant metastasis rates for National Comprehensive
      Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and
      high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three
      tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%,
      29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which
      were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C
      indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to
      0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the
      Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using
      NCCN low/intermediate/high would be reclassified by the new three-tier system and
      67% of patients would be reclassified from NCCN six-tier (very-low- to very-high
      risk) by the new six-tier system. Conclusion A commercially available genomic
      classifier in combination with standard clinicopathologic variables can generate
      a simple-to-use clinical-genomic risk grouping that more accurately identifies
      patients at low, intermediate, and high risk for metastasis and can be easily
      incorporated into current guidelines to better risk-stratify patients.

PMID- 29185874
TI  - "She Finally Smiles ... for Real": Reducing Depressive Symptoms and Bolstering
      Resilience Through a Camp Intervention for LGBTQ Youth.
AB  - While summer camps are a recognized evidence-based strategy for building social
      and emotional skills among youth (U.S. Centers for Disease Control and Prevention
      [CDC], 2009), no known studies have evaluated the effects of camp programming for
      LGBTQ youth in the United States. This pilot study evaluates a novel program
      (Brave Trails) for LGBTQ youth ages 12 to 20, using a pre-post camper survey (N =
      56) and a post-camp parent survey (N = 54). Results show campers experienced
      increases in identity affirmation and hope and a reduction in depressive
      symptoms. Regression analyses found changes in identity affirmation predicted
      reductions in depressive symptoms and increases in resilience. Additionally,
      campers' experience of key camp programming features predicted changes in
      depressive symptoms. Findings from the parent survey were consistent with camper
      survey results. Theoretical and practical implications are discussed.

PMID- 29185873
TI  - In Vivo Determination of Mitochondrial Respiration in 1-Methyl-4-Phenyl-1,2,3,6
      Tetrahydropyridine-Treated Zebrafish Reveals the Efficacy of Melatonin in
      Restoring Mitochondrial Normalcy.
AB  - Although mitochondria dysfunction is related to multiple diseases, no in vivo
      studies are available on mitochondrial respiration in animal parkinsonian models.
      Our aim is to analyze in vivo mitochondrial respiration, which reflects changes
      in mitochondrial bioenergetics more precisely than in vitro mitochondrial
      preparations. These experiments can be carried out in zebrafish embryos, which
      were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) from 24 to
      72 hours postfertilization (hpf). A reduction in electron transfer system
      capacity, ATP turnover, and increased proton leak were observed at 72 hpf in MPTP
      treated embryos. These changes were followed by a significant oxidative stress
      due to inhibition in antioxidative defense and autophagy impairment. After
      removing MPTP from the treatment at 72 hpf, these bioenergetic deficiencies
      persisted up to 120 hpf. The administration of melatonin to zebrafish embryos at
      72 hpf, when mitochondrial dysfunction is already present, restored the
      respiratory capacity and ATP production, reduced oxidative stress, and normalized
      autophagy after 48 h. Melatonin also counteracted mortality and embryonic
      malformations due to MPTP. Our results confirm for the first time the efficacy of
      melatonin in restoring parkinsonian phenotypes in animals.

PMID- 29185876
TI  - Freezing for love: enacting 'responsible' reproductive citizenship through egg
      freezing.
AB  - The promise of egg freezing for women's fertility preservation entered feminist
      debate in connection with medical and commercial control over, and emancipation
      from, biological reproduction restrictions. In this paper we explore how women
      negotiate and make sense of the decision to freeze their eggs. Our analysis draws
      on semi-structured interviews with 16 women from the Midwest and East Coast
      regions of the USA who froze their eggs. Rather than freezing to balance career
      choices and 'have it all', the women in this cohort were largely 'freezing for
      love' and in the hope of having their 'own healthy baby'. This finding extends
      existing feminist scholarship and challenges bioethical concerns about egg
      freezing by drawing on the voices of women who freeze their eggs. By viewing egg
      freezing as neither exclusively liberation nor oppression or financial
      exploitation, this study casts egg freezing as an enactment of 'responsible'
      reproductive citizenship that 'anticipates coupledom' and reinforces the genetic
      relatedness of offspring.

PMID- 29185875
TI  - Immunization of Mice by Rotavirus NSP4-VP6 Fusion Protein Elicited Stronger
      Responses Compared to VP6 Alone.
AB  - Due to the limitations and safety issues of the two currently approved live
      attenuated rotavirus (RV) vaccines "RotaTeq and Rotarix," studies on
      nonreplicating sources of RV vaccines and search for proper RV antigens are
      actively carried out. The adjuvant activity of NSP4 and highly immunogenic
      properties of RV VP6 protein prompted us to consider the construction of a
      NSP4112-175-VP6 fusion protein and to assess the anti-VP6 IgG, IgA, and IgG
      subclass responses induced by Escherichia coli-derived NSP4-VP6 fusion protein
      compared to that of VP6 protein with/without formulation in Montanide ISA 50V2
      (M50) in BALB/c mice. Results indicated to the proper expression of the fused
      NSP4-VP6 and VP6 proteins in E. coli. Intraperitoneal immunization by M50
      formulated NSP4-VP6 fusion protein (M5+NSP4-VP6) induced the highest titration of
      VP6-specific IgG and IgA responses compared to the other groups. Indeed, the
      presence of NSP4 resulted to the induction of stronger humoral immune responses
      against the fused protein compared to that elicited by administration of VP6
      protein alone (with/without M50 formulation), implying the adjuvant properties of
      NSP4 for the fused protein. Moreover, the "M50+NSP4-VP6" formulation induced
      higher serum IgG2a titers than IgG1 and increased Interferon-gamma levels,
      despite unchanged interleukin-4 amounts compared to other groups, indicating Th1
      oriented responses with a possible role of NSP4. In conclusion, this study
      further highlights the potentiality of NSP4-VP6 fusion protein as an efficient
      and cost-effective immunogen in the field of RV vaccine development.

PMID- 29185878
TI  - Using Problem-solving Therapy to Improve Problem-solving Orientation, Problem
      solving Skills and Quality of Life in Older Hemodialysis Patients.
AB  - OBJECTIVES: To determine the effectiveness of Problem-Solving Therapy (PST) in
      older hemodialysis (HD) patients by assessing changes in health-related quality
      of life and problem-solving skills. METHODS: 33 HD patients in an outpatient
      hemodialysis center without active medical and psychiatric illness were enrolled.
      The intervention group (n = 15) received PST from a licensed social worker for 6
      weeks, whereas the control group (n = 18) received usual care treatment. RESULTS:
      In comparison to the control group, patients receiving PST intervention reported
      improved perceptions of mental health, were more likely to view their problems
      with a positive orientation and were more likely to use functional problem
      solving methods. Furthermore, this group was also more likely to view their
      overall health, activity limits, social activities and ability to accomplish
      desired tasks with a more positive mindset. CONCLUSIONS: The results demonstrate
      that PST may positively impact mental health components of quality of life and
      problem-solving coping among older HD patients. CLINICAL IMPLICATIONS: PST is an
      effective, efficient, and easy to implement intervention that can benefit problem
      solving abilities and mental health-related quality of life in older HD patients.
      In turn, this will help patients manage their daily living activities related to
      their medical condition and reduce daily stressors.

PMID- 29185877
TI  - Evaluation of a Direct Immunofluorescent Assay and/or Conjunctival Cytology for
      Detection of Canine Distemper Virus Antigen.
AB  - Canine distemper is a common and potentially lethal multisystemic disease caused
      by the Canine distemper virus (CDV). We evaluated the diagnostic performance of
      direct immunofluorescent assay (FA) and cytology to detect CDV antigen in
      conjunctival cells compared with an established polymerase chain reaction (PCR)
      detection assay used as a gold standard for CDV diagnosis. Samples were collected
      from 57 young dogs presenting with central nervous system signs compatible with
      distemper disease. Exfoliative epithelial cells were collected from the right and
      left conjunctiva of each animal using nylon-bristled cytobrushes for cytology and
      cotton swabs for FA and PCR. For the direct FA, samples were stained with anti
      CDV polyclonal antiserum conjugated to fluorescein isothiocyanate and imaged
      using a fluorescent microscope. Out of 57 dogs tested, 19 were PCR positive (15
      positive in direct FA and 4 positive in cytology, including one that was negative
      by PCR), whereas 37 dogs were negative in all methods. A good agreement was
      observed between the FA and PCR, with a kappa-value of 0.833 (95% CI: 0.678
      0.989). Meanwhile, there was poor agreement between cytology and PCR (kappa-value
      of 0.164; 95% CI: -0.045 to 0.373) and a fair agreement between FA and cytology
      (kappa-value of 0.231; 95% CI: -0.026 to 0.487). Our results indicated a poor
      performance of cytology for the detection of CDV antigen. In contrast, FA is a
      100% specific and an adequately sensitive assay (sensitivity: 78.95%, negative
      likelihood ratio: 0.21, 95% CI: 0.09-0.50) for antemortem diagnosis of canine
      distemper.

PMID- 29185879
TI  - Early Conceptual Understanding of Cardinality Predicts Superior School-Entry
      Number-System Knowledge.
AB  - We demonstrate a link between preschoolers' quantitative competencies and their
      school-entry knowledge of the relations among numbers (number-system knowledge).
      The quantitative competencies of 141 children (69 boys) were assessed at the
      beginning of preschool and throughout the next 2 years of preschool, as was their
      mathematics and reading achievement at the end of kindergarten and their number
      system knowledge at the beginning of first grade. A combination of Bayes analyses
      and standard regressions revealed that the age at which the children had the
      conceptual insight that number words represent specific quantities (cardinal
      value) was strongly related to their later number-system knowledge and was more
      consistently related to broader mathematics than to reading achievement,
      controlling for intelligence, executive function, and parental education levels.
      The key implication is that it is not simply knowledge of cardinal value but the
      age of acquisition of this principle that is central to later mathematical
      development and school readiness.

PMID- 29185881
TI  - Essay Review: The Chemical Gatekeeper.

PMID- 29185880
TI  - Reviews.

PMID- 29185883
TI  - Blowpipes and Batteries: Humphry Davy, Edward Daniel Clarke, and Experimental
      Chemistry in Early Nineteenth-Century Britain.

PMID- 29185885
TI  - A JACN Tribute to Dr. Ananda S. Prasad (PhD, MD, FACN, MACN).

PMID- 29185884
TI  - Ozonation of polyoxymethylene effluent in a rotating packed bed.
AB  - This work aimed to investigate the effectiveness of ozone in degradation of
      polyoxymethylene (POM) effluent in a rotating packed bed (RPB) (O3-RPB system).
      The degradation efficiency was evaluated in terms of chemical oxygen demand
      (COD), 5-day biological oxygen demand (BOD5) and BOD5/COD under various operating
      conditions. Pilot experiments comprising the O3-RPB unit coupled with a
      biological contact oxidation unit were also carried out. The COD removal rates in
      the pilot process increased markedly to about 70-85% compared to about 40% in the
      original treatment process, which is the tertiary aerobic treatment in the plant,
      confirming that the O3-RPB system is very efficient in improving the
      biodegradability of the POM effluent.

PMID- 29185886
TI  - Fish Oil Suppresses Body Fat Accumulation in Zebrafish.
AB  - Zebrafish is an often used model of vertebrate lipid metabolism. In this article,
      we examined the effects of diets rich in fish oil, a dietary fat that has been
      shown to have antiobesity effects in mammals, or lard on body fat accumulation in
      zebrafish. Adult female zebrafish were fed a high-fat diet containing 20% (w/w)
      fish oil or lard for 4 weeks. Fish in the fish oil diet group had less body fat
      accumulation compared with those in the lard diet group. In the intestine,
      expression of genes for the alpha (hadhaa) and beta (hadhb) subunits of the beta
      oxidation enzyme hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A
      thiolase/enoyl-Coenzyme A hydratase was significantly increased in the fish oil
      diet group compared with the lard diet group (p < 0.05). In the liver, expression
      of the gene for fatty acid synthase (fasn) was significantly decreased in the
      fish oil diet group compared with the lard diet group (p < 0.05). These results
      suggest that the mechanisms underlying the antiobesity effect of fish oil are
      similar in zebrafish and mammals.

PMID- 29185887
TI  - Stratified or personalised medicine in the treatment of psoriasis?

PMID- 29185889
TI  - Report.

PMID- 29185888
TI  - Conduct Disorder Symptoms and Illicit Drug Use in Juvenile Justice Involved
      Youth: The Reciprocal Relationship Between Positive Illicit Drug-Use Attitudes
      and Illicit Drug Use.
AB  - Conduct disorder (CD) symptoms cooccur at high rates with illicit drug use in
      juvenile justice involved youth, which results in poorer outcomes; however,
      research has not identified where best to intervene in this relationship,
      limiting the identification of modifiable risk factors to reduce negative effects
      of CD symptoms. Two mediation models were examined to investigate the potential
      for CD symptoms to influence a reciprocal relationship between illicit drug use
      and positive drug attitudes, controlling for age, gender, and race. Data were
      examined for 245 juvenile justice involved youth (mean age = 15.46, SD = 1.30,
      range 12-18, 64.9% Black, 80.4% male) who completed court-ordered psychological
      assessments. Findings indicate: (1) Positive attitudes toward illicit drug use
      significantly mediated the relationship between CD symptoms and illicit drug use
      (beta = 0.16, CI 0.09-0.27; test for indirect effect z = 4.17, p < .001) and (2)
      illicit drug use significantly mediated the relationship between CD symptoms and
      positive attitudes toward illicit drug use (beta = 0.20, CI 0.12-0.32; test for
      indirect effect z = 4.87, p < .001). Overall, the present study suggests that CD
      symptoms impart risk for illicit drug use both indirectly, through more positive
      attitudes toward illicit drug use, and directly, which further strengthens
      positive attitudes toward illicit drug use.

PMID- 29185890
TI  - Justus Von Liebig, Eben Horsford and the Development of the Baking Powder
      Industry.

PMID- 29185891
TI  - Essay Review.

PMID- 29185892
TI  - Reviews.

PMID- 29185894
TI  - Student Perceptions of Sectional CT/MRI Use in Teaching Veterinary Anatomy and
      the Correlation with Visual Spatial Ability: A Student Survey and Mental
      Rotations Test.
AB  - Diagnostic imaging technology is becoming more advanced and widely available to
      veterinary patients with the growing popularity of veterinary-specific computed
      tomography (CT) and magnetic resonance imaging (MRI). Veterinary students must,
      therefore, be familiar with these technologies and understand the importance of
      sound anatomic knowledge for interpretation of the resultant images. Anatomy
      teaching relies heavily on visual perception of structures and their function. In
      addition, visual spatial ability (VSA) positively correlates with anatomy test
      scores. We sought to assess the impact of including more diagnostic imaging,
      particularly CT/MRI, in the teaching of veterinary anatomy on the students'
      perceived level of usefulness and ease of understanding content. Finally, we
      investigated survey answers' relationship to the students' inherent baseline VSA,
      measured by a standard Mental Rotations Test. Students viewed diagnostic imaging
      as a useful inclusion that provided clear links to clinical relevance, thus
      improving the students' perceived benefits in its use. Use of CT and MRI images
      was not viewed as more beneficial, more relevant, or more useful than the use of
      radiographs. Furthermore, students felt that the usefulness of CT/MRI inclusion
      was mitigated by the lack of prior formal instruction on the basics of CT/MRI
      image generation and interpretation. To be of significantly greater use, addition
      of learning resources labeling relevant anatomy in tomographical images would
      improve utility of this novel teaching resource. The present study failed to find
      any correlation between student perceptions of diagnostic imaging in anatomy
      teaching and their VSA.

PMID- 29185893
TI  - Milestone Educational Planning Initiatives in Veterinary Medical Education:
      Progress and Pitfalls.
AB  - Three milestone educational planning initiatives engaged the veterinary medical
      profession in the United States and Canada between 1987 and 2011, namely the Pew
      National Veterinary Education Program, the Foresight Project, and the North
      American Veterinary Medical Education Consortium. In a quantitative study, we
      investigated the impact of these initiatives on veterinary medical education
      through a survey of academic leaders (deans, previous deans, and associate deans
      for academics from veterinary medical schools that are members of the Association
      of American Veterinary Medical Colleges) to assess their perspectives on the
      initiatives and eight recommendations that were common to all three initiatives.
      Two of the recommendations have in effect been implemented: enable students to
      elect in-depth instruction and experience within a practice theme or discipline
      area (tracking), and increase the number of graduating veterinarians. For three
      of the recommendations, awareness of the issues has increased but substantial
      progress has not been made: promote diversity in the veterinary profession,
      develop a plan to reduce student debt, and develop a North American strategic
      plan. Lastly, three recommendations have not been accomplished: emphasize use of
      information more than fact recall, share educational resources to enable a cost
      effective education, and standardize core admissions requirements. The
      educational planning initiatives did provide collaborative opportunities to
      discuss and determine what needs to change within veterinary medical education.
      Future initiatives should explore how to avoid and overcome obstacles to
      successful implementation.

PMID- 29185895
TI  - Training Method and Other Factors Affecting Student Accuracy in Bovine Pregnancy
      Diagnosis.
AB  - To optimize bovine pregnancy diagnosis (PD) training, factors influencing student
      performance were investigated. The objective was to determine whether training
      method, gender, background (farm, urban, or mixed), previous experience in bovine
      PD, and current career interest influenced the accuracy of bovine PD by trans
      rectal palpation (TRP). Fourth-year (of a 6-year program) veterinary students
      (n=138) received one PD training session in groups using either simulator
      training on Breed'n Betsy (BB) or training on live cows (C). Students completed a
      questionnaire on gender, background, and career interest. Students' PD accuracy
      (pregnancy status and stage) was determined after training when each student
      palpated six cows with known pregnancy status. Students' accuracy in determining
      pregnancy status was measured as sensitivity and specificity (the ability to
      correctly identify the presence and absence of pregnancy respectively). Factors
      that influenced overall accuracy with a higher student sensitivity of bovine PD
      by TRP were training method, farming background, an interest in a mixed animal
      career, and stage of gestation. Gender of students and previous experience in
      bovine PD did not have an influence. Training on BB simulators was associated
      with lower student sensitivity for pregnancy detection in cows <6 months
      pregnant. Student sensitivity for pregnancy detection in cows >6 months pregnant
      was similar for training on BB simulators and live cows. No evaluated factors
      were significantly associated with specificity of PD. Teaching efforts focusing
      on specificity of PD and repeated simulator-based training in conjunction with
      live cow exposure are recommended.

PMID- 29185897
TI  - Pharmacological Treatment of Insomnia Symptoms in Individuals with Substance Use
      Disorders in Spain: A Quasi-Experimental Study.
AB  - INTRODUCTION: Pharmacological treatment of insomnia in patients with addictions
      has been hardly investigated and there are few researches about it in an
      inpatient detoxification. The aim of this study was to describe the outcomes of
      the pharmacological treatment of insomnia in SUD patients admitted to a
      detoxification unit in Spain, with a focus on the primary substance of abuse and
      co-occurring mental disorders. METHODS: A quasi-experimental study was conducted
      in 481 addicted in patients, who were admitted for substances detoxification in
      Vall d'Hebron University Hospital, Barcelona, Spain, from 2010 to 2015. The
      patients underwent systematic evaluation of axes I and II psychiatric disorders
      (SCID-I, SCID-II, and CAADID). Insomnia was evaluated using a night time sleep
      log. Substance-dependent patients, who had insomnia during hospital
      detoxification, received a psychotropic medication with hypnotic effect, keeping
      the regular clinical practice without randomization. RESULTS: At discharge,
      insomnia was considered to have been alleviated in 63.8% (n = 204) of patients
      while 36.2% (n = 116) of patients remained with insomnia disturbances. Comparing
      hypnotic treatments it was observed that mirtazapine and clotiapine were the
      treatment that corrected the insomnia more frequently. DISCUSSION: Since insomnia
      is not corrected in all patients, it should be further investigated in
      medications with hypnotic purpose. Based on the results of this work, randomized
      clinical trials might be proposed.

PMID- 29185896
TI  - Impact of Expert Commentary and Student Reflection on Veterinary Clinical
      Decision-Making Skills in an Innovative Electronic-Learning Case-Based Platform.
AB  - One challenge in veterinary education is bridging the divide between the nature
      of classroom examples (well-defined problem solving) and real world situations
      (ill-defined problem solving). Solving the latter often relies on experiential
      knowledge, which is difficult to impart to inexperienced students. A
      multidisciplinary team including veterinary specialists and learning scientists
      developed an interactive, e-learning case-based module in which students made
      critical decisions at five specific points (Decision Points [DPs]). After
      committing to each decision (Original Answers), students reflected on the thought
      processes of experts making similar decisions, and were allowed to revise their
      decisions (Revised Answers); both sets of answers were scored. In Phase I,
      performance of students trained using the module (E-Learning Group) and by
      lecture (Traditional Group) was compared on the course final examination. There
      was no difference in performance between the groups, suggesting that the e
      learning module was as effective as traditional lecture for content delivery. In
      Phase II, differences between Original Answers and Revised Answers were evaluated
      for a larger group of students, all of whom used the module as the sole method of
      instruction. There was a significant improvement in scores between Original and
      Revised Answers for four out of five DPs (DP1, p =.004; DP2, p =.04; DP4, p
      <.001; DP5, p <.001). The authors conclude that the ability to rehearse clinical
      decision making through this tool, without direct individual feedback from an
      instructor, may facilitate students' transition from problem solving in a well
      structured classroom setting to an ill-structured clinical setting.

PMID- 29185898
TI  - Both enantiomers of 6'-Isoneplanocin.
AB  - Both enantiomers of the isomer of neplanocin where the C-4' hydroxymethyl has
      been displaced to the 6'-position (that is, 6'-isoneplanocin) have been prepared
      in 5 steps from known, protected iodocyclopentenones. Both products were
      evaluated against a number of DNA and RNA viruses and found to be inactive. This
      observation is suggested to be due to the displacement of the C-4' hydroxymethyl
      of neplanocin (in the D-like form) away from the lysine425 of S
      adenosylhomocysteine hydrolase, which is important for inhibition by neplanocin
      and, in turn, its antiviral activity.

PMID- 29185899
TI  - Vaccination coverage and factors associated with adherence to the vaccination
      schedule in young children of a rural area in Burkina Faso.
AB  - BACKGROUND: Vaccination is an important tool for reducing infectious disease
      morbidity and mortality. In the past, less than 80% of children 12-23 months of
      age were fully immunized in Burkina Faso. OBJECTIVES: To describe coverage and
      assess factors associated with adherence to the vaccination schedule in rural
      area Burkina Faso. METHODS: The study population was extracted from the Nouna
      Health and Demographic surveillance system cohort. Data from four rounds of
      interviews conducted between November 2012 and June 2014 were considered. This
      study included 4016 children aged 12-23 months. We assessed the effects of
      several background factors, including sex, factors reflecting access to health
      care (residence, place of birth), and maternal factors (age, education, marital
      status), on being fully immunized defined as having received Bacillus Calmette
      Guerin (BCG), three doses of diphtheria-tetanus-pertussis and oral polio vaccine,
      and measles vaccine by 12 months of age. The associations were studied using
      binomial regression to derive prevalence ratios (PRs) in univariate and
      multivariate regression models. RESULTS: The full vaccination coverage increased
      significantly over time (72% in 2012, 79% in 2013, and 81% in 2014, p = 0.003),
      and the coverage was significantly lower in urban than in rural areas (PR 0.84;
      0.80-0.89). Vaccination coverage was neither influenced by sex nor influenced by
      place of birth or by maternal factors. CONCLUSION: The study documented a further
      improvement in full vaccination coverage in Burkina Faso in recent years and
      better vaccination coverage in rural than in urban areas. The organization of
      healthcare systems with systematic outreach activities in the rural areas may
      explain the difference between rural and urban areas.

PMID- 29185900
TI  - Intercalation of a Zn(II) complex containing ciprofloxacin drug between DNA base
      pairs.
AB  - In this study, an attempt has been made to study the interaction of a Zn(II)
      complex containing an antibiotic drug, ciprofloxacin, with calf thymus DNA using
      spectroscopic methods. It was found that Zn(II) complex could bind with DNA via
      intercalation mode as evidenced by: hyperchromism in UV-Vis spectrum; these
      spectral characteristics suggest that the Zn(II) complex interacts with DNA most
      likely through a mode that involves a stacking interaction between the aromatic
      chromophore and the base pairs of DNA. DNA binding constant (Kb = 1.4 * 104 M-1)
      from spectrophotometric studies of the interaction of Zn(II) complex with DNA is
      comparable to those of some DNA intercalative polypyridyl Ru(II) complexes 1.0 
      4.8 * 104 M-1. CD study showed stabilization of the right-handed B form of DNA in
      the presence of Zn(II) complex as observed for the classical intercalator
      methylene blue. Thermodynamic parameters (DeltaH < 0 and DeltaS < 0) indicated
      that hydrogen bond and Van der Waals play main roles in this binding prose.
      Competitive fluorimetric studies with methylene blue (MB) dye have shown that
      Zn(II) complex exhibits the ability of this complex to displace with DNA-MB,
      indicating that it binds to DNA in strong competition with MB for the
      intercalation.

PMID- 29185901
TI  - Identification of Distant Metastatic Disease in Uterine Cervical and Endometrial
      Cancers with FDG PET/CT: Analysis from the ACRIN 6671/GOG 0233 Multicenter Trial.
AB  - Purpose To assess the accuracy of staging positron emission tomography
      (PET)/computed tomography (CT) in detecting distant metastasis in patients with
      local-regionally advanced cervical and high-risk endometrial cancer in the
      clinical trial by the American College of Radiology Imaging Network (ACRIN) and
      the Gynecology Oncology Group (GOG) (ACRIN 6671/GOG 0233) and to compare central
      and institutional reader performance. Materials and Methods In this prospective
      multicenter trial, PET/CT and clinical data were reviewed for patients enrolled
      in ACRIN 6671/GOG 0233. Two central readers, blinded to site read and reference
      standard, reviewed PET/CT images for distant metastasis. Central review was then
      compared with institutional point-of-care interpretation. Reference standard was
      pathologic and imaging follow-up. Test performance for central and site reviews
      of PET/CT images was calculated and receiver operating characteristic analysis
      was performed. Generalized estimating equations and nonparametric bootstrap
      procedure for clustered data were used to assess statistical significance.
      Results There were 153 patients with cervical cancer and 203 patients with
      endometrial cancer enrolled at 28 sites. Overall prevalence of distant metastasis
      was 13.7% (21 of 153) for cervical cancer and 11.8% (24 of 203) for endometrial
      cancer. Central reader PET/CT interpretation demonstrated sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value of
      54.8%, 97.7%, 79.3%, and 93.1% for cervical cancer metastasis versus 64.6%,
      98.6%, 86.1%, and 95.4% for endometrial cancer, respectively. By comparison,
      local institutional review demonstrated sensitivity, specificity, PPV, and
      negative predictive value of 47.6%, 93.9%, 55.6%, and 91.9% for cervical cancer
      metastasis and 66.7%, 93.9%, 59.3%, and 95.5% for endometrial cancer,
      respectively. For central readers, the specificity and PPV of PET/CT detection of
      cervical and endometrial cancer metastases were all significantly higher compared
      with that of local institutional review (P < .05). Central reader area under the
      receiver operating characteristic curve (AUC) values were 0.78 and 0.89 for
      cervical and endometrial cancer, respectively; these were not significantly
      different from local institutional AUC values (0.75 and 0.84, respectively; P >
      .05 for both). Conclusion FDG PET/CT demonstrates high specificity and PPV for
      detecting distant metastasis in cervical and endometrial cancer and should be
      included in the staging evaluation. Blinded central review of imaging provides
      improved specificity and PPV for the detection of metastases and should be
      considered for future oncologic imaging clinical trials. (c) RSNA, 2017.

PMID- 29185903
TI  - Redpilling: A professional reflects on white racial privilege and drug policy in
      American health care.
AB  - The landscape of American health care is changing under the weight of new
      knowledge that health care workers-physicians, nurses, and so on-are abusing the
      drugs that they use within health care. In this article, the author uses
      ethnographic data (including his own work in American pharmacies over the past
      two decades) to contextualize how health care's drug abuse epidemic is racially
      coded to ignore the fact that White Americans are the primary drug abusers-what
      he calls "redpilling." In pointing out the racial contexts of health care's drug
      abuse, the author asks whether our national "war on drugs" ought to be recast to
      see how White racial privilege-the privilege of White Americans to comfortably
      perform certain actions (and get away with them if they are illegal or morally
      wrong)-mandates that we move the lens of drug policy from ghettos and ethnic
      communities to American health care where we have been historically positioned to
      not identify White American health care workers who work while high.

PMID- 29185902
TI  - Intermanufacturer Comparison of Dual-Energy CT Iodine Quantification and
      Monochromatic Attenuation: A Phantom Study.
AB  - Purpose To determine the accuracy of dual-energy computed tomographic (CT)
      quantitation in a phantom system comparing fast kilovolt peak-switching, dual
      source, split-filter, sequential-scanning, and dual-layer detector systems.
      Materials and Methods A large elliptical phantom containing iodine (2, 5, and 15
      mg/mL), simulated contrast material-enhanced blood, and soft-tissue inserts with
      known elemental compositions was scanned three to five times with seven dual
      energy CT systems and a total of 10 kilovolt peak settings. Monochromatic images
      (50, 70, and 140 keV) and iodine concentration images were created. Mean iodine
      concentration and monochromatic attenuation for each insert and reconstruction
      energy level were recorded. Measurement bias was assessed by using the sum of the
      mean signed errors measured across relevant inserts for each monochromatic energy
      level and iodine concentration. Iodine and monochromatic errors were assessed by
      using the root sum of the squared error of all measurements. Results At least one
      acquisition paradigm per scanner had iodine biases (range, -2.6 to 1.5 mg/mL)
      with significant differences from zero. There were no significant differences in
      iodine error (range, 0.44-1.70 mg/mL) among the top five acquisition paradigms
      (one fast kilovolt peak switching, three dual source, and one sequential
      scanning). Monochromatic bias was smallest for 70 keV (-12.7 to 15.8 HU) and
      largest for 50 keV (-80.6 to 35.2 HU). There were no significant differences in
      monochromatic error (range, 11.4-52.0 HU) among the top three acquisition
      paradigms (one dual source and two fast kilovolt peak switching). The lowest
      accuracy for both measures was with a split-filter system. Conclusion Iodine and
      monochromatic accuracy varies among systems, but dual-source and fast kilovolt
      switching generally provided the most accurate results in a large phantom. (c)
      RSNA, 2017 Online supplemental material is available for this article.

PMID- 29185906
TI  - Molecular Identification of Cryptosporidium spp. in Iranian Dogs Using Seminested
      PCR: A First Report.
AB  - Cryptosporidium is a parasitic protozoon with a wide range of vertebrate hosts.
      Cryptosporidiosis has been reported from numerous countries, including Iran.
      Molecular identification can be applied to characterize Cryptosporidium, of which
      there are over 30 species and 50 genotypes. Herein, we report the genetic
      diversity of Cryptosporidium spp. in Iranian dogs for the first time based on 18S
      ribosomal RNA gene sequencing. One hundred forty fecal samples of herd dogs were
      collected from Isfahan, central Iran. The samples were concentrated using sucrose
      flotation and subjected to Kinyoun staining. DNA extraction of positive samples
      was performed, and molecular diagnosis was carried out using highly specific
      seminested PCR for the characterization of Cryptosporidium species. Finally,
      sequencing and DNA analysis were performed to identify Cryptosporidium species. A
      total of 2.14% of herd dogs were positive for cryptosporidiosis in both
      microscopy and molecular methods. In all cases, the causative agent was
      identified as Cryptosporidium parvum. Dogs associated with positive samples had
      been in close relationship with livestock. Cryptosporidiosis in the herd dogs in
      Isfahan could be due to their close contact with animals, particularly cattle and
      sheep. Given that dogs with cryptosporidiosis lack clinical symptoms, they are a
      potential source of zoonotic transmission of this disease as they are companion
      animals for humans. Dogs with cryptosporidiosis are a potential source of the
      zoonotic transmission of this disease.

PMID- 29185908
TI  - Dual-substrate inhibition kinetic studies for recombinant human interferon gamma
      producing Pichia pastoris.
AB  - Pichia pastoris is considered as one of the prominent host extensively used as a
      platform for heterologous protein production. In the present study, the growth
      inhibition kinetics of recombinant P. pastoris expressing human interferon gamma
      was studied under different initial substrate concentrations of gluconate (10-100
      g L-1) and methanol (2-50 g L-1) in modified FM22 medium. The highest specific
      growth rate of 0.0206 and 0.019 hr-1 was observed at 60 g L-1 of gluconate and 10
      g L-1 of methanol, respectively. Various three- and four-parametric Monod-variant
      models were chosen to analyze the inhibition kinetics. The model parameters as
      well as goodness of fit were estimated using nonlinear regression analysis. The
      three-parameter Haldane model was found to be best fit for both gluconate (R2 =
      0.95) and methanol substrate (R2 = 0.96). The parameter sensitivity analysis
      revealed that umax, Ki, and Ks are the most sensitive parameters for both
      methanol and gluconate. Different substrate inhibition models were fitted to the
      growth kinetic data and the additive form of double Webb model was found to be
      the best to explain the growth kinetics of recombinant P. pastoris.

PMID- 29185909
TI  - The effects of a neutral cosolute on the B to Z transition for DNA duplexes
      incorporating both CG and CA steps.
AB  - In the cell, nearly 40% of the volume is occupied by macromolecular crowding
      agents and smaller osmolytes accumulate in response to environmental stresses. Of
      particular interest is the influence of osmolytes on the transition of the right
      handed B-DNA to the left-handed Z-DNA. Due to the correlation between Z-DNA
      formation potential and regions of active transcription, Z-DNA is believed to
      serve a vital role in the transcription process, and changes in osmolyte
      concentration may influence transcription as a part of the stress response. We
      utilized circular dichroism spectroscopy to monitor changes in conformation of
      DNA duplexes containing a full-turn of Z-DNA in the presence and absence of PEG
      200. We used PEG 200 as a model neutral cosolute. Sodium ion titrations revealed
      that PEG 200 influenced the folding of Z-DNA compared to dilute solution
      conditions by decreasing the free energy of folding, increasing folding
      cooperativity, and decreasing the in vitro [Na+] and Deltan required for folding
      for all sequences tested, even those that included 40% CA steps instead of the
      classic CG repeats. Moreover, the presence of 40% PEG 200 induced the Z-form
      conformation in sequences that would not fully adopt the Z-form structure even in
      5 M NaCl. These results suggest that osmolytes may play a significant role in
      supporting the transient formation of Z-DNA in vivo, and that sequences
      containing a significant amounts of CA instead of CG repeats may more favorably
      adopt the Z-conformation as a part of binding and regulatory processes than had
      been previously considered.

PMID- 29185910
TI  - A Critical Analysis and Applied Intersectionality Framework with Intercultural
      Queer Couples.
AB  - Intercultural queer couples are growing at an extensive rate in the United
      States, exemplifying diversity across multiple dimensions (e.g., race, ethnicity,
      sexuality, affectional identity, gender identity) while experiencing multiple
      converging forms of oppression (e.g., racism, heterosexism, genderism). Given the
      dearth of conceptual and empirical literature that unifies both dimensions
      related to intercultural and queer, applied practices and research contend with a
      unilateral approach focusing exclusively on either intercultural or queer
      couples. Intersectionality theory has revolutionized critical scholarship to
      determine overlapping forms of oppression, decenter hegemonic structures of power
      relations and social contexts, and enact a social justice agenda. This article
      addresses the following aims: (1) an overview of the gaps eliciting unilateral
      approaches to intercultural queer couples; (2) an illustration of
      intersectionality's theoretical underpinnings as a critical approach; and (3)
      applications for insights in practices and research with intercultural queer
      couples.

PMID- 29185911
TI  - "I Don't Believe in Leading a Life of My Own, I Lead His Life": A Qualitative
      Investigation of Difficulties Experienced by Informal Caregivers of Stroke
      Survivors Experiencing Depressive and Anxious Symptoms.
AB  - OBJECTIVES: Health and social care services are increasingly reliant on informal
      caregivers to provide long-term support to stroke survivors. However, caregiving
      is associated with elevated levels of depression and anxiety in the caregiver
      that may also negatively impact stroke survivor recovery. This qualitative study
      aims to understand the specific difficulties experienced by caregivers
      experiencing elevated symptoms of anxiety and depression. METHODS: Nineteen semi
      structured interviews were conducted with caregivers experiencing elevated levels
      of depression and anxiety, with a thematic analysis approach adopted for
      analysis. RESULTS: Analysis revealed three main themes: Difficulties adapting to
      the caring role; Uncertainty; and Lack of support. CONCLUSIONS: Caregivers
      experienced significant difficulties adapting to changes and losses associated
      with becoming a caregiver, such as giving up roles and goals of importance and
      value. Such difficulties persisted into the long-term and were coupled with
      feelings of hopelessness and worry. Difficulties were further exacerbated by
      social isolation, lack of information and poor long-term health and social care
      support. CLINICAL IMPLICATIONS: A greater understanding of difficulties
      experienced by depressed and anxious caregivers may inform the development of
      psychological support targeting difficulties unique to the caring role. Improving
      caregiver mental health may also result in health benefits for stroke survivors
      themselves.

PMID- 29185912
TI  - Jonson and Sendivogius: Some New Light on Mercury Vindicated from the Alchemists
      at Court.

PMID- 29185914
TI  - Letters to the Reviews Editor.

PMID- 29185913
TI  - The Fate of Bacon's Cosmology in the Seventeenth Century.

PMID- 29185915
TI  - Antibiotic Resistance Gene Detection in the Microbiome Context.
AB  - Within the past decade, microbiologists have moved from detecting single
      antibiotic resistance genes (ARGs) to detecting all known resistance genes within
      a sample due to advances in next generation sequencing. This has provided a
      wealth of data on the variation and relative abundances of ARGs present in a
      total bacterial population. However, to use these data in terms of therapy or
      risk to patients, they must be analyzed in the context of the background
      microbiome. Using a quantitative PCR ARG chip and 16S rRNA amplicon sequencing,
      we have sought to identify the ARGs and bacteria present in a fecal sample of a
      healthy adult using genomic tools. Of the 42 ARGs detected, 12 fitted into the
      ResCon1 category of ARGs: cfxA, cphA, bacA, sul3, aadE, blaTEM, aphA1, aphA3,
      aph(2')-Id, aacA/aphd, catA1, and vanC. Therefore, we describe these 12 genes as
      the core resistome of this person's fecal microbiome and the remaining 30 ARGs as
      descriptors of the microbial population within the fecal microbiome. The dominant
      phyla and genera agree with those previously detected in the greatest abundances
      in fecal samples of healthy humans. The majority of the ARGs detected were
      associated with the presence of specific bacterial taxa, which were confirmed
      using microbiome analysis. We acknowledge the limitations of the data in the
      context of the limited sample set. However, the principle of combining qPCR and
      microbiome analysis was shown to be helpful to identify the association of the
      ARGs with specific taxa.

PMID- 29185916
TI  - Drug-Drug Interactions in Cocaine-users and their Clinical Implications.
AB  - BACKGROUND: Drug-Drug Interactions (DDIs) represent a common problem in clinical
      practice during drug treatments. DDIs can both induce the development of adverse
      drug reactions or reduce the clinical efficacy of each drug. OBJECTIVES: The main
      objective of this review was to analyze the pharmacokinetic and pharmacodynamic
      DDIs in cocaine consumers, focusing the interest on their clinical implications.
      METHODS: The PubMed, Embase and Cochrane library databases were searched for
      articles published until January 10, 2017. Secondary search included articles
      cited in reference lists identified by the primary search. Papers were deemed
      eligible if they included any form of words: "adverse drug reaction", "drug
      interactions", "poly-therapy", "cocaine", "systemic diseases". RESULTS: In this
      review, the nodal points treated concern: i) cocaine biochemical metabolism
      described for both, inactive benzoylecgonine and ecgonine methyl esters and
      norcocaine active metabolites. We provided evidences of concepts deriving from
      rat/mice experimental studies speculating a translation approach to human in
      order to treat cocaine overdose. ii) Drug-drug interactions, which come out from
      clinical evidences as the case of CYP450 family enzyme inhibitors or inductors
      modulating cocaine toxicity. Particularly, we highlighted the lack of knowledge
      concerning cocaine and CYP3A4 inhibitors (such as ketoconazole, nefazodone,
      erythromycin, and clarithromycin). We recorded the worst association of cocaine
      and beta-blockers by direct and indirect action, particularly at postsynaptic
      levels on dopamine and norepinephrine reuptake, sympathetic activation and
      increase of heart rate, blood pressure and cardiovascular toxicity. Cocaine also
      induces increase in serotonin synaptic activity leading to the development of a
      serotoninergic syndrome when used with drugs that affect serotonin pathway.
      Genetic (i.e. glutathione peroxidase-1 deficiency) and epigenetic factors (i.e.
      microRNAs) may be involved in drug-drug interactions in cocaine-users are also
      being introduced. CONCLUSION: DDIs represent an important potential complication
      in cocaine users in clinical setting. The knowledge of DDIs can also be used to
      select treatments for patients, thus optimizing clinical response and minimizing
      toxicity.

PMID- 29185919
TI  - COLORFUL ENGINEERING.
AB  - Advances in fluorescent dye and protein design have led to a wider color palette
      for microscopy. Nathan Blow explores how this happened and what is still to come.

PMID- 29185920
TI  - A TB40/E-derived human cytomegalovirus genome with an intact US-gene region and a
      self-excisable BAC cassette for immunological research.
AB  - For immunological research on the human cytomegalovirus (HCMV), a virus that
      combines the broad cell tropism of clinical isolates, efficient replication in
      cell culture, the complete set of MHC-I modulator genes, and suitability for
      genetic engineering is desired. Here, we aimed to generate a genetically complete
      derivative of HCMV strain TB40/E as a bacterial artificial chromosome (BAC) with
      a self-excisable BAC cassette. The BAC cassette was inserted into the US2-US6
      gene region (yielding TB40-BACKL7), relocated into the UL73/UL74 region with
      modifications that favor excision of the BAC cassette during replication in
      fibroblasts, and finally the US2-US6 region was restored, resulting in BAC clone
      TB40-BACKL7-SE When this BAC clone was transfected into fibroblasts at
      efficiencies >0.1%, replicating virus that had lost the BAC cassette appeared
      within 2 weeks after transfection, grew to high titers, and displayed the broad
      tropism of the parental virus. The degree of MHC-I down-regulation by this virus
      was consistent with functional restoration of US2-US6. To enable detection of
      infected cells by flow cytometry, an enhanced green fluorescent protein (EGFP)
      expression cassette was inserted downstream of US34A, yielding the fluorescent
      virus RV-TB40-BACKL7-SE-EGFP.

PMID- 29185921
TI  - Mouse Behavior Tracker: An economical method for tracking behavior in home cages.
AB  - Analysis of mouse behavior often requires expensive equipment and transfer of the
      mice to new test environments, which could trigger confounding behavior
      alterations. Here, we describe a system for tracking mouse behavior in home cages
      using a low-cost USB webcam and free software (Fiji and wrMTrck). We demonstrate
      the effectiveness of this method by tracking differences in distance traveled,
      speed, and movement tracks between wild-type mice and amyotrophic lateral
      sclerosis (ALS) model mice (SOD1G93A).

PMID- 29185922
TI  - Incorporation of unique molecular identifiers in TruSeq adapters improves the
      accuracy of quantitative sequencing.
AB  - Quantitative analysis of next-generation sequencing (NGS) data requires
      discriminating duplicate reads generated by PCR from identical molecules that are
      of unique origin. Typically, PCR duplicates are identified as sequence reads that
      align to the same genomic coordinates using reference-based alignment. However,
      identical molecules can be independently generated during library preparation.
      Misidentification of these molecules as PCR duplicates can introduce unforeseen
      biases during analyses. Here, we developed a cost-effective sequencing adapter
      design by modifying Illumina TruSeq adapters to incorporate a unique molecular
      identifier (UMI) while maintaining the capacity to undertake multiplexed, single
      index sequencing. Incorporation of UMIs into TruSeq adapters (TrUMIseq adapters)
      enables identification of bona fide PCR duplicates as identically mapped reads
      with identical UMIs. Using TrUMIseq adapters, we show that accurate removal of
      PCR duplicates results in improved accuracy of both allele frequency (AF)
      estimation in heterogeneous populations using DNA sequencing and gene expression
      quantification using RNA-Seq.

PMID- 29185923
TI  - ReViMS: Software tool for estimating the volumes of 3-D multicellular spheroids
      imaged using a light sheet fluorescence microscope.
AB  - Cancer 3-D spheroids are widely used to test drugs and radiotherapy treatments.
      These 3-D cell clusters range from tens to hundreds of micrometers in size, with
      shapes that typically differ from a perfect sphere. Change in spheroid volume is
      one of the most important parameters for evaluating treatment efficacy, and using
      light sheet fluorescence microscopes (LSFM), optical sections of samples in that
      size range can be obtained. However, there remains a lack of validated methods
      for quantifying the volumes of 3-D multicellular aggregates. Here, we present
      Reconstruction and Visualization from Multiple Sections (ReViMS), an open-source,
      user-friendly software for automatically segmenting z-stacks of fluorescence
      images and estimating the volumes of 3-D multicellular spheroids. To assess the
      precision and accuracy of the volume estimates obtained with ReViMS, we used
      several cancer spheroids imaged with LSFM. Both the precision and accuracy were
      >95%, demonstrating the effectiveness of ReViMS.

PMID- 29185924
TI  - Protocol for adhesion and immunostaining of lymphocytes and other non-adherent
      cells in culture.
AB  - Immunostaining of non-adherent cells is commonly performed after adhesion of
      cells onto microscope slides either using cytocentrifugation or with the help of
      charged coating substrates. These techniques, however, require either specialized
      equipment or significant preparation time. Here, we describe a method for
      immunofluorescent staining of lymphocytes within multi-well culture plates, where
      cells suspended in phosphate buffered saline (PBS) are adhered to either the
      plastic well bottom or glass coverslips by gravity sedimentation. This technique
      requires only common laboratory materials, no coating steps, and allows for
      densely adherent cell coverage with 1 * 106 cells. Our data show that suspension
      of cells in PBS, but not serum-containing growth medium, allows for adhesion to
      plastic or glass after 30 min of gravity sedimentation. We show that this method
      is applicable for immunofluorescent staining of both primary human lymphocytes
      and immortalized lymphoma cells, and that it preserves cell morphology.

PMID- 29185928
TI  - Dietary intake, nutritional status and mental wellbeing of homeless adults in
      Reading, UK.
AB  - Malnutrition has been reported in the homeless, yet the specific nutritional
      issues faced by each homeless community are unclear. This is in part due to
      nutrient intake often being compared with dietary reference values as opposed to
      a comparative housed population. In addition, the complex interplay between
      nutrient intake, reward mediated behaviour and mental illness is frequently
      overlooked. This study aimed to compare the dietary intake, nutritional status
      and mental wellbeing of homeless and housed adults. Homeless (n 75) and matched
      housed (n 75) adults were recruited from Reading (UK). Nutrient intake was
      determined using the European Prospective Investigation into Cancer and Nutrition
      Norfolk FFQ. The Patient Health Questionnaire: Somatic Anxiety Depressive
      Symptoms (PHQ-SADS) assessed for signs of mental illness. Demographic,
      behavioural and physiological information was collected using closed-ended
      questions and anthropometric measurements. Overall, dietary intake was poorer in
      homeless adults who reported higher intakes of salt (8.0 v. 6.4 g, P=0.017), SFA
      (14.6 v. 13.0 %, P=0.002) and alcohol (5.3 v. 1.9 %, P<0.001) and lower intakes
      of fibre (13.4 v. 16.3 g, P<0.001), vitamin C (79 v. 109 mg, P<0.001) and fruit
      (96 v. 260 g, P<0.001) than housed. Smoking, substance misuse and PHQ-SADS scores
      were also higher in the homeless (P<0.001). Within the homeless population,
      street homeless (n 24) had lower SFA (13.7 v.15.0 %, P=0.010), Ca (858 v. 1032
      mg, P=0.027) and milk intakes (295 v. 449 g, P=0.001) than hostel residents (n
      51), which may reflect the issues with food storage. This study highlights the
      disparity between nutritional status in homeless and housed populations and the
      need for dietary intervention in the homeless community.

PMID- 29185927
TI  - Supplemental psyllium fibre regulates the intestinal barrier and inflammation in
      normal and colitic mice.
AB  - Our previous study demonstrated that supplemental psyllium fibre increased
      cytoprotective heat-shock protein (Hsp) 25 levels in the intestinal cells of
      mice. Here, we examined the effect of psyllium fibre on colonic gene and protein
      expression and faecal microbiota in normal and colitic mice to improve the
      understanding of the preventive role of the supplement. DNA microarray analysis
      revealed that a 10 % psyllium fibre diet administered for 5 d up-regulated eleven
      extracellular matrix (ECM)-associated genes, including collagens and
      fibronectins, in normal mice. Acute colitis was induced using dextran sodium
      sulphate (DSS) in mice that were administered a pre-feeding 5 to 10 % psyllium
      fibre diet for 5 d. Psyllium fibre partially ameliorated or resolved the DSS
      induced colon damage and inflammation characterised by body weight loss, colon
      shortening, increased levels of pro-inflammatory cytokines and decreased tight
      junction protein expression in the colon. Analysis of faecal microbiota using
      denaturing gradient gel electrophoresis of the PCR-amplified 16S rRNA gene
      demonstrated that psyllium fibre affected the colonic microbiota. Intestinal
      permeability was evaluated by growing intestinal Caco-2 cell monolayers on
      membrane filter supports coated with or without fibronectin and collagen. Cells
      grown on collagen and fibronectin coating showed higher transepithelial
      electrical resistance, indicating a strengthening of barrier integrity.
      Therefore, increased Hsp25 levels and modification of colonic ECM contribute to
      the observed psyllium-mediated protection against DSS-induced colitis.
      Furthermore, ECM modification appears to play a role in the strengthening of the
      colon barrier. In conclusion, psyllium fibre may be useful in the prevention of
      intestinal inflammatory diseases.

PMID- 29185929
TI  - Impact of a non-restrictive satiating diet on anthropometrics, satiety
      responsiveness and eating behaviour traits in obese men displaying a high or a
      low satiety phenotype.
AB  - The aim of this study was to evaluate the impact of a non-restrictive satiating
      diet in men displaying various degrees of satiety efficiency. In all, sixty-nine
      obese men aged 41.5 (sd 5.7) years were randomly assigned to a control (10-15, 55
      60 and 30 % energy as protein, carbohydrate and lipid, respectively; n 34) or
      satiating (20-25, 45-50 and 30-35 % energy as protein, carbohydrate and lipid,
      respectively; n 35) diet for 16 weeks, and were classified as having a low (LSP)
      or high (HSP) satiety phenotype. Both diets were consumed ad libitum. Changes in
      body weight, BMI, percent fat mass, waist circumference, satiety responsiveness
      and eating behaviour traits were assessed following the intervention. Dropout
      rates were higher in the control diet (44.1 %) compared with the satiating diet
      (8.6 %). Decreases in body weight, BMI and waist circumference were significant
      in both groups, yet HSP individuals lost more body weight than LSP individuals
      (P=0.048). Decreases in % fat mass were greater in the satiating diet (LSP: -2.1
      (sd 2.1) %; P<0.01 and HSP: -3.0 (sd 2.5) %; P<0.001) compared with the control
      diet (LSP: -1.1 (sd 2.5) % and HSP: -1.3 (sd 2.6) %) (P=0.034). Satiety
      responsiveness was markedly improved in the satiating diet, whereas no
      significant changes were observed in the control group. Changes in dietary
      restraint (+3.3 (sd 2.9) to +7.2 (sd 5.5)), flexible control (+0.9 (sd 1.4) to
      +2.3 (sd 2.7)), rigid control (+2.2 (sd 1.5) to +2.5 (sd 2.8)), disinhibition (
      2.8 (sd 3.7) to -3.2 (sd 2.6)) and susceptibility to hunger (-2.7 (sd 4.1) to 
      4.6 (sd 3.9)) were similar between the diets. Compared with the control diet, the
      satiating diet favoured adherence, decreased % fat mass and improved satiety
      responsiveness in both HSP and LSP individuals.

PMID- 29185930
TI  - Impact of sourdough fermentation on appetite and postprandial metabolic responses
      - a randomised cross-over trial with whole grain rye crispbread.
AB  - Sourdough fermentation is considered to have beneficial effects on postprandial
      satiety and metabolic responses, but studies demonstrating effects at
      physiological conditions are lacking. The aim of this acute breakfast
      intervention study was to determine the effect of consumption of sourdough
      fermented and unfermented rye crispbread on self-rated appetite, postprandial
      glucose and insulin response in healthy subjects. In all, twenty-four Swedish
      adults were included in a single-blinded, randomised cross-over trial. Three
      crispbreads (sourdough-fermented and unfermented whole grain rye and yeast
      fermented refined wheat as control) were consumed as part of a standardised
      breakfast. Subjective appetite score, assessed using visual analogue scale, and
      plasma glucose and insulin concentrations were measured at baseline and
      postprandially until 360 and 240 min, respectively. Structural changes and
      viscosity during mastication and gastric digestion were investigated using in
      vitro methods. Hunger and desire to eat were lower (P<0.05) based on AUC
      measurements after intake of sourdough-fermented rye crispbread compared with
      after intake of yeast-fermented refined wheat crispbread. On the basis of AUC (0
      230 min), insulin response was lowest after intake of unfermented rye crispbread
      compared with sourdough-fermented rye and yeast-fermented refined wheat
      crispbread. Degradation of viscous fibres and faster bolus disintegration for the
      sourdough-fermented bread may partly explain the less favourable metabolic
      responses compared with unfermented bread. Our results showed that food
      processing affects the composition and structural characteristics of rye bread,
      which has implications for appetite and metabolic responses.

PMID- 29185931
TI  - Effect of aggregation form on bioavailability of zeaxanthin in humans: a
      randomised cross-over study.
AB  - Carotenoid bioavailability from plant and animal food is highly variable
      depending on numerous factors such as the physical deposition form of
      carotenoids. As the carotenoid zeaxanthin is believed to play an important role
      in eye and brain health, we sought to compare the human bioavailability of an H
      aggregated with that of a J-aggregated deposition form of zeaxanthin encapsulated
      into identical formulation matrices. A randomised two-way cross-over study with
      sixteen participants was designed to compare the post-prandial bioavailability of
      an H-aggregated zeaxanthin and a J-aggregated zeaxanthin dipalmitate formulation,
      both delivering 10 mg of free zeaxanthin. Carotenoid levels in TAG-rich
      lipoprotein fractions were analysed over 9.5 h after test meal consumption.
      Bioavailability from the J-aggregated formulation (AUC=55.9 nmol h/l) was 23 %
      higher than from the H-aggregated one (AUC=45.5 nmol h/l), although being only
      marginally significant (P=0.064). Furthermore, the same formulations were
      subjected to an internationally recognised in vitro digestion protocol to reveal
      potential strengths and weaknesses of simulated digestions. In agreement with our
      human study, liberation of zeaxanthin from the J-aggregated formulation into the
      simulated duodenal fluids was superior to that from the H-aggregated form.
      However, micellization rate (bioaccessibility) of the J-aggregated zeaxanthin
      dipalmitate was lower than that of the H-aggregated zeaxanthin, being
      contradictory to our in vivo results. An insufficient ester cleavage during
      simulated digestion was suggested to be the root cause for these observations. In
      brief, combining our in vitro and in vivo observations, the effect of the
      different aggregation forms on human bioavailability was lower than expected.

PMID- 29185932
TI  - Effects of partial replacement of maize in the diet with crude glycerin and/or
      soyabean oil on ruminal fermentation and microbial population in Nellore steers.
AB  - The objective of this study was to determine whether a combination of crude
      glycerin (CG) and soyabean oil (SO) could be used to partially replace maize in
      the diet of Nellore steers while maintaining optimum feed utilisation. Eight
      castrated Nellore steers fitted with ruminal and duodenal cannulas were used in a
      double 4*4 Latin square design balanced for residual effects, in a factorial
      arrangement (A*B), when factor A corresponded to the provision of SO, and factor
      B to the provision of CG. Steers feed SO and CG showed similar DM intake, DM,
      organic matter and neutral-detergent fibre digestibility to that of steers fed
      diets without oil and without glycerine (P>0.05). Both diets with CG additions
      reduced the acetate:propionate ratio and increased the proportion of iso
      butyrate, butyrate, iso-valerate and valerate (P<0.05). Steers fed diets
      containing SO had less total N excretion (P<0.001) and showed greater retained N
      expressed as % N intake (P=0.022). SO and CG diet generated a greater ruminal
      abundance of Prevotella, Succinivibrio, Ruminococcus, Syntrophococcus and
      Succiniclasticum. Archaea abundance (P=0.002) and total ciliate protozoa were
      less in steers fed diets containing SO (P=0.011). CG associated with lipids could
      be an energy source, which is a useful strategy for the partial replacement of
      maize in cattle diets, could result in reduced total N excretion and ruminal
      methanogens without affecting intake and digestibility.

PMID- 29185933
TI  - Severe riboflavin deficiency induces alterations in the hepatic proteome of
      starter Pekin ducks.
AB  - Suboptimal vitamin B2 status is encountered globally. Riboflavin deficiency
      depresses growth and results in a fatty liver. The underlying mechanisms remain
      to be established and an overview of molecular alterations is lacking. We
      investigated hepatic proteome changes induced by riboflavin deficiency to explain
      its effects on growth and hepatic lipid metabolism. In all, 360 1-d-old Pekin
      ducks were divided into three groups of 120 birds each, with twelve replicates
      and ten birds per replicate. For 21 d, the ducks were fed ad libitum a control
      diet (CAL), a riboflavin-deficient diet (RD) or were pair-fed with the control
      diet to the mean daily intake of the RD group (CPF). When comparing RD with CAL
      and CPF, growth depression, liver enlargement, liver lipid accumulation and
      enhanced liver SFA (C6 : 0, C12 : 0, C16 : 0, C18 : 0) were observed. In RD,
      thirty-two proteins were enhanced and thirty-one diminished (>1.5-fold) compared
      with CAL and CPF. Selected proteins were confirmed by Western blotting. The
      diminished proteins are mainly involved in fatty acid beta-oxidation and the
      mitochondrial electron transport chain (ETC), whereas the enhanced proteins are
      mainly involved in TAG and cholesterol biosynthesis. RD causes liver lipid
      accumulation and growth depression probably by impairing fatty acid beta
      oxidation and ETC. These findings contribute to our understanding of the
      mechanisms of liver lipid metabolic disorders due to RD.

PMID- 29185934
TI  - The relationships among iron supplement use, Hb concentration and linear growth
      in young children: Ethiopian Demographic and Health Survey.
AB  - Growth faltering and anaemia remain unacceptably high among infants and young
      children in Ethiopia. In this study, we investigated the relationships among Fe
      supplement use (ISU), Hb concentration and linear growth, hypothesising positive
      relationships between ISU and Hb, ISU and linear growth and Hb and linear growth.
      We used a nationally representative data of 2400 children aged 6-24 months from
      the Ethiopian Demographic and Health Survey (EDHS) 2011, conducted following a
      stratified, two-stage cluster sampling. We examined the links by Pearson's
      correlation, bivariate and multivariate linear regression analyses and reported
      adjusted estimates. We found that ISU was not significantly associated with
      either Hb (beta=1.09; 95 % CI -2.73, 5.01, P=0.567) or linear growth (beta=0.07;
      95 % CI -0.06, 0.21, P=0.217). We found a positive, however, weak, correlation
      between Hb and linear growth (r 0.09; 95 % CI 0.06, 0.11, P<0.001). Hb predicted
      linear growth independent of a variety dietary and non-dietary factors
      (beta=0.08; 95 % CI 0.04, 0.11, P<0.001). Although not the primary focus of the
      study, our analysis showed that age and breast-feeding duration were
      independently associated with Hb; age, birth type, size at birth, sex, breast
      feeding duration, dietary diversity and deworming were independently associated
      with linear growth, indicating that Hb and linear growth are multifactorial with
      both nutritional and non-nutritional factors implicated. Further studies, with
      better design and exposure assessment, are warranted on the relation of ISU with
      Hb or linear growth.

PMID- 29185935
TI  - DHA mediates the protective effect of fish consumption on new episodes of
      depression among women.
AB  - In a longitudinal cohort study of young Australian adults, we reported that for
      women higher baseline levels of fish consumption were associated with reduced
      incidence of new depressive episodes during the 5-year follow-up. Fish are high
      in both n-3 fatty acids and tyrosine. In this study, we seek to determine whether
      n-3 fatty acids or tyrosine explain the observed association. During 2004-2006, a
      FFQ (nine fish items) was used to estimate weekly fish consumption among 546
      women aged 26-36 years. A fasting blood sample was taken and high-throughput NMR
      spectroscopy was used to measure 233 metabolites, including serum n-3 fatty acids
      and tyrosine. During 2009-2011, new episodes of depression since baseline were
      identified using the lifetime version of the Composite International Diagnostic
      Interview. Relative risks were calculated using log-binomial regression and
      indirect effects estimated using the STATA binary_mediation command. Potential
      mediators were added to separate models, and mediation was quantified as the
      proportion of the total effect due to the mediator. The n-3 DHA mediated 25.3 %
      of the association between fish consumption and depression when fish consumption
      was analysed as a continuous variable and 16.6 % when dichotomised (reference
      group: <2 serves/week). Tyrosine did not mediate the association (<0.1 %).
      Components in fish other than n-3 fatty acids and tyrosine might be beneficial
      for women's mental health.

PMID- 29185936
TI  - Consumption of preserved egg, a high-lead-containing food, is strongly associated
      with depressive symptoms in Chinese adults.
AB  - Previous studies have demonstrated adverse mental health effects of Pb exposure.
      The purpose of this study is to investigate the relationship between consumption
      of preserved egg (PE), a high-Pb-containing food and depressive symptoms among
      adults in China. A sample of 25 213 adults (mean age 41.4 (sd 11.8) years; males,
      53.9 %) in Tianjin, China, was studied in a cross-sectional analysis. Dietary
      intake including PE was assessed using a valid self-administered FFQ. Depressive
      symptoms were assessed using the Self-Rating Depression Scale (SDS). The
      association was estimated by OR using logistic regression models adjusted for
      multiple confounders. The prevalence of elevated depressive symptoms was 6.6 %
      (SDS>=50). Compared with the least frequent PE consumption (<once/week),
      multivariable adjusted OR for elevated depressive symptoms were 1.52 (95 % CI
      1.28, 1.81), 2.24 (95 % CI 1.76, 2.81) and 3.31 (95 % CI 2.52, 4.30) for
      consumption of once, 2-3 times and >=4 times/week, respectively (P for
      trend<0.0001), indicating a clear dose-response relationship. The results
      suggested that higher consumption of PE was strongly associated with depressive
      symptoms among adults in China. These findings underscore the need to consider
      dietary Pb exposure as a risk factor for psychological distress.

PMID- 29185938
TI  - Thauera propionica sp. nov., isolated from downstream sediment sample of the
      river Ganges, Kanpur, India.
AB  - A Gram-stain-negative, non-endospore-producing, short-rod strain, KNDSS-Mac4T,
      was isolated from a downstream sediment sample of the river Ganges, Kanpur, India
      and studied by using the polyphasic taxonomic approach. 16S rRNA gene sequence
      analysis uncovered that the strain had similarity to species of the genus Thauera
      and formed a distinct phylogenetic cluster with Thauera humireducens KACC16524T.
      However, KNDSS-Mac4T showed closest phylogenetic affiliation to Thauera
      aminoaromatica DSM 14742T with 16S rRNA gene sequence similarity of 98.7 %
      followed by Thauera phenylacetica DSM 14743T (98.6 %), Thauera chlorobenzoica
      (98.2 %), T. humireducens KACC16524T (98.2 %), Thauera selenatis ATCC 55363T
      (98.2 %) and Thauera mechernichensis DSM 12266T (98.0 %). The digital DNA-DNA
      hybridization and average nucleotide identity values between strain KNDSS-Mac4T
      and the two most closely related taxa, T. aminoaromatica DSM 14742T and T.
      phenylacetica DSM 14743T, were 26.0, 26.7 and 84.0, 84.3 % respectively. Major
      lipids present were phosphatidylglycerol, three unknown aminophospholipids,
      phosphatidylmethylethanolamine, two unidentified lipids and Q-8 as the only
      ubiquonone. The major cellular fatty acids present were C16 : 1 omega6c/C16 :
      1omega7c and C16 : 0. The DNA G+C content of strain KNDSS-Mac4T was 65.9 %. Based
      on data from phenotypic tests and the genotypic differences of strain KNDSS-Mac4T
      from its closest phylogenetic relatives, it is evident that this isolate should
      be regarded as a new species. It is proposed that strain KNDSS-Mac4T should be
      classified in the genus Thauera as a novel species, Thauerapropionica sp. nov.
      The type strain is KNDSS-Mac4T (=KCTC 52820T=VTCC-B-910017T).

PMID- 29185937
TI  - Fastidiosibacter lacustris gen. nov., sp. nov., isolated from a lake water
      sample, and proposal of Fastidiosibacteraceae fam. nov. within the order
      Thiotrichales.
AB  - AFrancisella-like bacterium, designated strain SYSU HZH-2T, was isolated from a
      water sample collected from Haizhu Lake, Guangzhou, China. The bacterium was
      fastidious, and required an exogenous source of l-cysteine for its growth on
      artificial media. Cells were Gram-stain-negative, coccobacilli, non-motile and
      non-spore-forming. The strain shared highest 16S rRNA gene sequence similarities
      with Cysteiniphilum litorale SYSU D3-2T (94.6 % identity), Fangia hongkongensis
      UST040201-002T (93.2 %) and Caedibacter taeniospiralis 51T (91.6 %). This strain
      possessed ubiquinone-8 as the respiratory quinone; diphosphatidylglycerol,
      phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol as the
      known polar lipids, and anteiso-C15 : 0 and C18 : 0 as the major fatty acids (>10
      % of total fatty acids). The dendrograms based on 16S rRNA gene sequence analysis
      showed that it formed a separate cluster along with Cysteiniphilum litorale SYSU
      D3-2T, Caedibactertaeiniospiralis 51T and Fangia hongkongensis UST040201-002T.
      Based on the 16S rRNA gene sequence identity and differences in other phenotypic
      characteristics, the strain is considered to represent a novel species of a novel
      genus, for which the name Fastidiosibacter lacustris gen. nov., sp. nov. is
      proposed. The type strain of the type species Fastidiosibacter lacustris is SYSU
      HZH-2T (=NBRC 112274T = CGMCC 1.15950T). Additionally, the new taxon along with
      the genera Caedibacter, Cysteiniphilum and Fangia (family unassigned) were
      distinctly separated from the related families Francisellaceae,
      Piscirickettsiaceae and Thiotrichaeae in the phylogenetic trees. Therefore, we
      proposed a new family Fastidiosibacteraceae fam. nov. within the order
      Thiotrichales to accommodate these four genera.

PMID- 29185939
TI  - Flavobacterium naphthae sp. nov., isolated from oil-contaminated soil.
AB  - During a study of petroleum hydrocarbon-degrading bacteria, a yellow-coloured,
      Gram-stain-negative, non-motile and rod-shaped bacterium, designated strain Brt
      MT, was isolated from oil-contaminated soil of Biratnagar, Morang, Nepal. Strain
      Brt-MT was able to grow at 15-45  degrees C, pH 5.0-9.0 and 0-1 % (w/v) NaCl
      concentration. The strain was characterized by multiple taxonomic approaches.
      Based on 16S rRNA gene sequence analysis, strain Brt-MT belonged to the genus
      Flavobacterium and shared highest sequence similarity with Flavobacterium cloacae
      wh15T (95.69 %) and Flavobacterium anatoliense MK3T (94.91 %). The only
      respiratory quinone was MK-6; the major polar lipid was phosphatidylethanolamine;
      and the predominant fatty acids were iso-C15 : 0, summed feature 9 (iso-C17 :
      1omega9c and/or C16 : 010-methyl), iso-C17 : 0 3-OH and summed feature 3 (C16 :
      1omega7c and/or C16 : 1omega6c). The DNA G+C content was 37.2 mol%. The
      morphological, physiological, chemotaxonomic and phylogenetic analyses clearly
      distinguished this strain from its closest phylogenetic neighbours. Thus, strain
      Brt-MT represents a novel species of the genus Flavobacterium, for which the name
      Flavobacteriumnaphthae sp. nov. is proposed. The type strain is Brt-MT (=KEMB
      9005-692T=KACC 19393T=JCM 32171T).

PMID- 29185940
TI  - Listeria monocytogenes cells under nutrient deprivation showed reduced ability to
      infect the human intestinal cell line HT-29.
AB  - PURPOSE: This study aimed to evaluate the effect of two types of stress, cold and
      nutritional, on the viability and the in vitro virulence of the foodborne
      pathogenic bacteria Listeria monocytogenes. METHODOLOGY: Ten diverse isolates
      were kept in phosphate-buffered saline (PBS) at optimal (37  degrees C) or at
      refrigeration temperature (7  degrees C), for 1 and 7 days. The viability of the
      cells [log colony-forming units (c.f.u.)/ml] and their in vitro virulence, before
      and after storage in these conditions, were investigated. In vitro virulence (log
      PFA) was evaluated using the human intestinal epithelial cell line HT-29 in
      plaque-forming assays (PFAs).Results/Key findings. In general, when compared with
      the conditions at 37  degrees C, the exposure at 7  degrees C for 7 days seemed
      to increase the resistance of the isolates to nutritional stress. Nutritional
      stress per se acted significantly to decrease the in vitro virulence of the
      isolates. After 7 days of nutrient deprivation, whether at optimal or at
      refrigeration temperature, the majority of the isolates assumed a low-virulence
      phenotype. CONCLUSION: Our results suggest that when L. monocytogenes are in
      refrigerated post-processing environments that are unable to support their growth
      they may increase their resistance to nutritional stress and may decrease their
      virulence. This should be considered when performing risk assessments for
      refrigerated ready-to-eat (RTE) foods.

PMID- 29185942
TI  - Abstracts Presented at the National Neonatal, Advanced Practice, and National
      Mother Baby Nurses Conference.

PMID- 29185941
TI  - Cell-wall recycling and synthesis in Escherichia coli and Pseudomonas aeruginosa 
      their role in the development of resistance.
AB  - The bacterial cell-wall that forms a protective layer over the inner membrane is
      called the murein sacculus - a tightly cross-linked peptidoglycan mesh unique to
      bacteria. Cell-wall synthesis and recycling are critical cellular processes
      essential for cell growth, elongation and division. Both de novo synthesis and
      recycling involve an array of enzymes across all cellular compartments, namely
      the outer membrane, periplasm, inner membrane and cytoplasm. Due to the
      exclusivity of peptidoglycan in the bacterial cell-wall, these players are the
      target of choice for many antibacterial agents. Our current understanding of cell
      wall biochemistry and biogenesis in Gram-negative organisms stems mostly from
      studies of Escherichia coli. An incomplete knowledge on these processes exists
      for the opportunistic Gram-negative pathogen, Pseudomonas aeruginosa. In this
      review, cell-wall synthesis and recycling in the various cellular compartments
      are compared and contrasted between E. coli and P. aeruginosa. Despite the fact
      that there is a remarkable similarity of these processes between the two
      bacterial species, crucial differences alter their resistance to beta-lactams,
      fluoroquinolones and aminoglycosides. One of the common mediators underlying
      resistance is the amp system whose mechanism of action is closely associated with
      the cell-wall recycling pathway. The activation of amp genes results in
      expression of AmpC beta-lactamase through its cognate regulator AmpR which
      further regulates multi-drug resistance. In addition, other cell-wall recycling
      enzymes also contribute to antibiotic resistance. This comprehensive summary of
      the information should spawn new ideas on how to effectively target cell-wall
      processes to combat the growing resistance to existing antibiotics.

PMID- 29185943
TI  - Why Do We Do What We Do?

PMID- 29185944
TI  - Achondroplasia: Etiology, Clinical Presentation, and Management.
AB  - By using a literature review, this article examines the implications of
      achondroplasia. The following areas are discussed: the clinical definition of the
      disease; the incidence, etiology, and pathogenesis; phenotypical characteristics
      and natural history of the disease; and management, recurrence risk, and genetic
      counseling. Lastly, implications for nursing in relation to achondroplasia are
      discussed.

PMID- 29185945
TI  - Alagille Syndrome: An Overview.
AB  - Alagille syndrome (AGS) is a highly complex, multisystem, autosomal dominant
      disorder that is caused by a defect in the Notch signaling pathway. This syndrome
      mainly affects the liver, causing significant cholestasis, which is caused by a
      paucity of intrahepatic bile ducts. There can be cardiac involvement, including,
      but not limited to, pulmonary stenosis and tetralogy of Fallot. Patients can also
      present with butterfly vertebra, ocular issues, and vascular events. Because this
      syndrome follows an autosomal dominant inheritance, it can have variable
      expression even in the same family line. For infants in the NICU who have a
      cardiac defect and persistent hyperbilirubinemia after two weeks of age, genetic
      testing for AGS should be considered. Early detection and diagnosis can lead to
      improved outcomes. In this discussion of AGS, the clinical features as well as
      management are discussed.

PMID- 29185946
TI  - Electronic Health Record Documentation of Nursing Care Procedures and Change in
      Weight of Healthy, Moderately Premature Neonates.
AB  - PURPOSE: To identify the nursing care procedures (NCPs) performed in a NICU that
      disrupt the thermal environment by opening the incubator of moderately preterm
      neonates (mPNs) (32-34 wk gestational age) and the relationship between the
      frequency of these disruptions and change in weight (Deltawt). DESIGN: Survey and
      descriptive correlational methodology. SAMPLE: Systematically identified,
      published references to NCPs that opening the incubator developed an itemized
      list of NCPs that was used to query the electronic health records (EHRs) of 164
      mPNs in the first ten days of life (DOL). MAIN OUTCOME VARIABLE: The Deltawt
      between birth and ten DOL. RESULTS: Of 51 NCPs identified, 26 were represented in
      the EHR. A mean of 614 (range 402-1,080; SD = 137) EHR-documented NCPs that
      opening the incubator were recorded. The frequency of NCPs was negatively
      correlated with the Deltawt of mPNs at ten DOL, rs (164) = -.162, p = .038.

PMID- 29185947
TI  - The Neonatal Eating Assessment Tool: Development and Content Validation.
AB  - PURPOSE: To develop and content validate the Neonatal Eating Assessment Tool
      (NeoEAT), a parent-report measure of infant feeding. DESIGN: The NeoEAT was
      developed in three phases. Phase 1: Items were generated from a literature
      review, available assessment tools, and parents' descriptions of problematic
      feeding in infants.Phase 2: Professionals rated items for relevance and clarity.
      Content validity indices were calculated. Phase 3: Parent understanding was
      explored through cognitive interviews. SAMPLE: Phase 1: Descriptions of infant
      feeding were obtained from 12 parents of children with diagnosed feeding problems
      and 29 parents of infants younger than seven months. Phase 2: Nine professionals
      rated items. Phase 3: Sixteen parents of infants younger than seven months
      completed the cognitive interview. MAIN OUTCOME VARIABLE: Content validity of the
      NeoEAT. RESULTS: Three versions were developed: NeoEAT Breastfeeding (72 items),
      NeoEAT Bottle Feeding (74 items), and NeoEAT Breastfeeding and Bottle Feeding (89
      items).

PMID- 29185948
TI  - Pneumopericardium in the Neonate.
AB  - Pneumopericardium occurs when air accumulates in the pericardial sac surrounding
      the heart and is one of the rarest forms of air leaks in neonates. Because of
      various advances in neonatal care, including gentler modes of ventilation,
      surfactant replacement, and antenatal steroids, the incidence of
      pneumopericardium has decreased. Despite the decrease in incidence of
      pneumopericardium, most cases arise in premature infants with a history of
      respiratory distress and mechanical ventilation. Evidence has shown that the
      incidence is inversely related to birth weight and that pneumopericardium has
      high mortality and morbidity rates.

PMID- 29185949
TI  - Atypical Presentation of Infantile Hepatic Hemangioma: A Case Study.
AB  - Infantile hepatic hemangioma (IHH) is the most common benign hepatic tumor of
      infancy. It is characterized by rapid proliferation in the first year of life,
      followed by slow involution during childhood. Presentation can range from
      asymptomatic to severe, high-output congestive heart failure (CHF). The purpose
      of this article is to review the case of an infant with an atypical presentation
      of IHH. It also addresses pathophysiology, diagnosis, management, and
      multidisciplinary team care.

PMID- 29185950
TI  - Procalcitonin and Neonatal Sepsis: Is This the Biomarker We Are Looking For?
AB  - Researchers estimate the incidence of early onset sepsis as 0.77-1/1,000 live
      births. It remains as one of the leading causes of neonatal deaths. Clinicians
      and researchers continue to search for biomarkers for specific neonatal disease
      processes. Clinicians frequently trend C-reactive protein levels during
      evaluation for neonatal sepsis. Recently, researchers have begun to explore
      procalcitonin as a potentially useful diagnostic marker for neonatal sepsis.

PMID- 29185951
TI  - Intraamniotic Infection and the Term Neonate.
AB  - Intraamniotic infection (IAI) may occur when the amniotic membranes are ruptured
      >18 hours prior to birth. The term neonate is at risk for early onset sepsis.
      This article describes the pathophysiology of IAI and the role of the mother-baby
      nurse during the anticipated birth and the ongoing assessment of the neonate.

PMID- 29185953
TI  - News of the Academy of Neonatal Nursing.

PMID- 29185952
TI  - Continuing Education Course.

PMID- 29185954
TI  - Divalent cations increase the conjugation efficiency of the incompatibility P-7
      group plasmid pCAR1 among different Pseudomonas hosts.
AB  - The incompatibility (Inc) P-7 group plasmid pCAR1 can be efficiently transferred
      among bacteria in artificial microcosms in the presence of divalent cations Ca2+
      and Mg2+. One-on-one mating assays between Pseudomonas strains with different
      plasmids showed that the promotion of conjugation efficiency by divalent cations
      was exhibited in other plasmids, including pB10 and NAH7; however, this effect
      was larger in IncP-7 plasmids. The impact on pCAR1 conjugation differed according
      to donor-recipient pairs, and conjugation efficiency promotion was clearly
      detected between the donors P. resinovorans CA10dm4 and P. fluorescens Pf0-1 and
      the recipients P. putida KT2440 and CA10dm4. Transcriptome analyses showed that
      pCAR1 gene expression did not respond to cation changes, including the tra/trh
      genes involved in its transfer. However, the transcription of oprH genes,
      encoding putative outer-membrane proteins in both the donor and the recipient,
      were commonly upregulated under cation-limited conditions. The conjugation
      frequency of pCAR1 in the KT2440 oprH mutant was found not to respond to cations.
      This effect was partially recovered by complementation with the oprH gene,
      suggesting that OprH is involved in the increase of pCAR1 conjugation efficiency
      by divalent cations.

PMID- 29185955
TI  - Paraburkholderia azotifigens sp. nov., a nitrogen-fixing bacterium isolated from
      paddy soil.
AB  - A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterial strain,
      designated NF2-5-3T, was isolated from a paddy soil in Anseong city, Republic of
      Korea. This bacterium was characterized to determine its taxonomic position using
      a polyphasic approach. On the basis of 16S rRNA gene sequence analysis, strain
      NF2-5-3T had a close relationship with, and was related most closely to, members
      of the genus Paraburkholderia, namely Paraburkholderia caribensis MWAP64T (98.8 %
      similarity), P. sabiae Br3407T (98.8 %), P. hospita LMG 20598T (98.5 %), P.
      terrae NBRC 100964T (98.3 %) and P. phymatum STM815T (98.1 %). Growth of strain
      NF2-5-3T occurred at 15-37  degrees C, at pH 6.0-8.0 and at NaCl concentrations
      of 0-2 % (w/v). The major respiratory quinone was ubiquinone 8 (Q-8) and the
      major fatty acids were C16 : 0, summed feature 8 (comprising C18 : 1omega7c
      and/or C18 : 1omega6c), C17 : 0 cyclo and C16 : 0 3-OH. The polar lipid profile
      consisted of phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine, an unidentified phospholipid, unidentified
      aminophospholipids, unidentified aminolipids and unidentified polar lipids. The
      G+C content of the genomic DNA was 64.2 mol%. DNA-DNA relatedness values between
      strain NF2-5-3T and its closest phylogenetic neighbours were much lower than 70
      %. Strain NF2-5-3T could be differentiated phylogenetically and phenotypically
      from recognized species of the genus Paraburkholderia. The isolate therefore
      represents a novel species, for which the name Paraburkholderia azotifigens sp.
      nov. is proposed, with NF2-5-3T (=KACC 18968T=LMG 29961T) as the type strain.

PMID- 29185956
TI  - Diagnostic value of BiP or anti-BiP antibodies for rheumatoid arthritis: a meta
      analysis.
AB  - OBJECTIVES: To evaluate the diagnostic value of BiP or anti-BiP antibodies in
      patients with rheumatoid arthritis. METHODS: Relevant studies published on PubMed
      and CNKI from January 1995 to July 2016 were retrieved. Two reviewers
      independently evaluated studies and QUADAS tool was used to assess the quality of
      the included studies. A random-effects model was used to combine sensitivity,
      specificity, positive and negative likelihood ratios and diagnostic odds ratio.
      Stratified analysis was performed for exploring heterogeneity and funnel plot was
      examined for the possibility of publication bias. RESULTS: Nine studies met our
      inclusion criteria. The pooled sensitivity, specificity, LR+, LR-, DOR were 0.67
      (95%CI, 0.64-0.70), 0.92 (95%CI, 0.90-0.93), 7.65(95%CI, 4.08-14.36), 0.36(95%CI,
      0.33-0.39), 23.73(95%CI, 13.01-43.28), respectively. CONCLUSIONS: This meta
      analysis shows that BiP or anti-BiP antibodies have a moderate accuracy for the
      diagnosis of rheumatoid arthritis with a moderate sensitivity and high
      specificity. It can be an efficient supplement to the existing diagnostic method.

PMID- 29185957
TI  - The utility of the ACR/EULAR 2017 provisional classification criteria for
      granulomatosis with polyangiitis in Korean patients with antineutrophil
      cytoplasmic antibody-associated vasculitis.
AB  - OBJECTIVES: We applied the ACR/EULAR 2017 provisional classification criteria for
      granulomatosis with polyangiitis (GPA) to 150 Korean patients with previously
      diagnosed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)
      and investigated how many patients with AAV were reclassified as GPA. METHODS: We
      included patients with 30 GPA, 30 eosinophilic GPA (EGPA) and 90 microscopic
      polyangiitis (MPA) patients. Patients can be classified as GPA, when the sum of
      scores is more than 5. RESULTS: At diagnosis the mean age of 150 patients with
      AAV was 60.1 years old, and 101 patients (67.3%) were women. Overall, 33 of 150
      patients with AAV (22.0%) were classified as GPA according to the 2017
      provisional criteria for GPA. The 2017 provisional criteria for GPA dropped to
      10.0% of previously diagnosed GPA patients and the major factor to drop 3 GPA
      patients was the deletion of 2 items of the 1990 criteria, urinary sediment and
      infiltrates on chest radiograph. Meanwhile, one of 30 patients with EGPA (3.3%)
      and 5 of 90 patients with MPA (5.6%) were newly classified as GPA based on the
      2017 provisional criteria for GPA. We could also find that items of the 2017
      provisional criteria to contribute to reclassifying EGPA and MPA patients as GPA
      were PR3-ANCA, mass-like lung lesion and nasal congestion in Korean patients with
      AAV. CONCLUSIONS: The use of the 2017 provisional criteria for GPA excluded 10.0%
      of previously classified GPA patients and newly classified 3.3% of EGPA patients
      and 5.6% of MPA patients as GPA in Korean patients with AAV.

PMID- 29185958
TI  - Are rheumatologists adhering to the concepts window of opportunity and treat-to
      target? Earlier and more intense disease-modifying anti-rheumatic drug treatment
      over time in patients with early arthritis in the PEARL study.
AB  - OBJECTIVES: To analyse changes over time in the treatment with disease modifying
      anti-rheumatic drugs and biological therapies prescribed to patients from an
      early arthritis register and whether these changes had an impact on their
      outcome. METHODS: This was a longitudinal retrospective 2-year study based on
      data collected in the PEARL study. The population was clustered in three groups
      depending on year of symptoms onset (2000-2004, 2005-2009, 2010-2014). Intensity
      of disease-modifying anti-rheumatic drug treatment was calculated and the
      percentage of patients receiving biological therapy during the first 2-year
      follow-up was collected. Disease activity and remission at the end of follow-up,
      as well as radiological progression were the outcomes analysed. Multivariable
      analyses were fitted to determine which variables including the three period
      times were associated with the outcomes. RESULTS: A significant increase in
      treatment intensity was observed in patients with undifferentiated arthritis,
      getting closer to that prescribed to patients fulfilling the 1987 RA criteria at
      the last period studied (2010-2014). This finding was associated with a
      significantly higher percentage of patients in remission and lower progression of
      the erosion component of the Sharp van der Heijde score. CONCLUSIONS: During the
      last 15 years, the treatment of patients with early arthritis in our hospital has
      been progressively increased and it has been associated with significantly better
      outcomes.

PMID- 29185959
TI  - Recommendations for the use of biologics and other novel drugs in the treatment
      of psoriatic arthritis: 2017 update from the Italian Society of Rheumatology.
AB  - OBJECTIVES: To update the 2011 Italian Society of Rheumatology (SIR)
      recommendations for the use of biologics and other novel agents in the treatment
      of psoriatic arthritis (PsA). METHODS: To create this new set of recommendations,
      the SIR "Spondyloartritis and Psoriatic Arthritis study group - A. Spadaro" went
      through the following steps: literature search, identification of the items of
      interests for each of the four previously identified clinical domains of PsA and
      the different treatment phases, achievement of the consensus on all topics, and
      generation of the recommendations. RESULTS: An update on the available evidence
      on all of the biologics and new small molecules tested in PsA is reported,
      comprising the data for each of the individual articular manifestation.
      Indications for therapy inclusion criteria, choice of the drug, disease
      assessment, response definition, therapy failure management, and disease
      remission management for PsA peripheral joint arthritis, enthesitis, dactylitis,
      and spondylitis are provided. Suggestions for the treatment of patients with PsA
      and concomitant extra-articular manifestations are also given. CONCLUSIONS: These
      evidence-based recommendations may be used for guidance in the complex and fast
      evolving field of the treatment of PsA.

PMID- 29185960
TI  - One year in review 2017: idiopathic inflammatory myopathies.
AB  - Every year new concepts about pathogenesis, serology, diagnosis and treatment in
      inflammatory myopathies (IIMs) have been provided. The purpose of this manuscript
      is to summarise the most relevant literature contributions published over the
      last year about these complex and rare diseases.

PMID- 29185961
TI  - Recommendations for the management of pulmonary fungal infections in patients
      with rheumatoid arthritis.
AB  - Often life-threatening pulmonary fungal infections (PFIs) can occur in patients
      with rheumatoid arthritis (RA) receiving disease-modifying anti-rheumatic drugs
      (DMARDs). Most of the data concerning PFIs in RA patients come from case reports
      and retrospective case series. Of the ve most widely described PFIs, Pneumocystis
      jirovecii pneumonia (PJP) has rarely been seen outside Japan, pulmonary
      cryptococcosis has been diagnosed in only a small number of patients worldwide,
      pulmonary coccidioidomycosis has almost only been observed in endemic areas, the
      limited number of cases of pulmonary histoplasmosis have mainly occurred in the
      USA, and the rare cases of invasive pulmonary aspergillosis have only been
      encountered in leukopenic patients. Many aspects of the prophylaxis, diagnosis
      and treatment of PFIs in RA patients remain to be defined, as does the role of
      each DMARD in increasing the risk of infection, and the possibility of resuming
      biological and non-biological DMARD treatment after the infection has been cured.
      The recommendations for the management of PFIs described in this paper are the
      product of a consensus procedure promoted by the Italian group for the Study and
      Management of Infections in Patients with Rheumatic Diseases (the ISMIR group).

PMID- 29185962
TI  - Renal outcome of kidney-transplantation in Korean recipients with ANCA-associated
      vasculitis.
AB  - OBJECTIVES: We investigated renal outcome of kidney-transplantation in Korean
      recipients with biopsy-proven renal involvement of antineutrophil cytoplasmic
      antibody (ANCA)-associated vasculitis (AAV) in a single centre. METHODS: We
      reviewed the medical records of 144 Korean patients and included 3 female
      patients with microscopic polyangiitis (MPA) and one male patient with
      eosinophilic granulomatosis with polyangiitis (EGPA) in this study. We obtained
      clinical and laboratory data related to kidney-transplantation, analysed renal
      outcome of kidney-transplantation in 4 recipients with AAV and compared it with
      those of previous studies. RESULTS: The mean age at diagnosis was 37.8 years and
      that at kidney-transplantation was 40.8 years. Time-gap from AAV to ESRD ranged
      from 1 to 48 months and that from AAV to kidney-transplantation ranged from 2 to
      95 months. All kidney-recipients with had been followed-up for two years or
      greater. At diagnosis, MPO-ANCA was detected in only MPA patients, while, at
      transplantation, MPA-ANCA was detected in 2 MPA patients and an EGPA patient. All
      patients have received tacrolimus and mycophenolate mofetil based on
      glucocorticoid after kidney-transplantation. Among 4 kidney-recipients with AAV,
      one MPA patient underwent renal re-biopsies three times due to renal function
      deterioration during the follow-up. Renal histology revealed T cell-mediated and
      antibody-mediated rejection rather than relapse of MPA. Neither relapse nor graft
      failure was observed in our study. CONCLUSIONS: Renal outcome of kidney
      transplantation in recipients with AAV was good and kidney-transplantation is
      deserved to be recommend as a safe and effective therapeutic modality to AAV
      patients with ESRD.

PMID- 29185964
TI  - Recurrence of mixed cryoglobulinaemia vasculitis following influenza vaccination
      despite clearance of hepatitis C virus infection.

PMID- 29185963
TI  - The therapeutic nuclear magnetic resonance changes the balance in intracellular
      calcium and reduces the interleukin-1beta induced increase of NF-kappaB activity
      in chondrocytes.
AB  - OBJECTIVES: Osteoarthritis as the main chronic joint disease is characterised by
      the destruction of articular cartilage. Developing new, more effective and in
      particular non-invasive methods to achieve pain reduction of OA patients are of
      exceptional interest. Clinical observations demonstrated positive effects of
      therapeutically applied low nuclear magnetic resonance (NMRT) for the treatment
      of painful disorders of the musculoskeletal system. In this study the cellular
      mechanism of action of NMRT was examined on chondrocytes. METHODS: Cal-78 human
      chondrosarcoma cells were kept under inflammatory conditions by application of IL
      1beta. NMRT treated cells were tested for changes in histamine induced Ca2+
      release by fura-2 calcium imaging. The effects of IL-1beta and of NMRT treatment
      were further tested by determining intracellular ATP concentrations and the
      activity of MAP-kinases and NF-kappaB. RESULTS: NMRT influenced the intracellular
      calcium signalling by elevating the basal [Ca2+]i. The peak calcium concentration
      evoked by 10 MUM histamine was increased by IL-1beta and this increase was
      reversed under NMRT treatment. Screening of different kinase-activities revealed
      an apparent increase in activity of MAPK/ERK and MAPK/JNK in NMRT stimulated
      cells, p38 was downregulated. The IL-1beta-induced decline in intracellular ATP
      and the elevated NF-kappaB activity was reversed under NMRT stimulation.
      CONCLUSIONS: Under inflammatory conditions, NMRT influenced cellular functions by
      modulating cellular calcium influx and/or calcium release. Further, NMRT induced
      changes in MAPK activities such as down-regulation of NF-kappaB and increasing
      intracellular ATP might help to stabilise chondrocytes and delay cartilage damage
      due to OA.

PMID- 29185965
TI  - Ultrasound changes in synovial abnormalities induced by treatment in juvenile
      idiopathic arthritis.
AB  - OBJECTIVES: To investigate the capacity of ultrasound (US) to detect improvement
      of synovial abnormalities induced by treatment in juvenile idiopathic arthritis
      (JIA). METHODS: Eighty-three joints (33 knees, 22 tibiotalar, 10 wrists, 9
      elbows, 9 subtalar joints) of 33 patients with new-onset JIA were assessed by US
      at study entry and 6 months after a therapeutic intervention. Each joint was
      scored for grey-scale (GS) and power Doppler (PD) abnormalities according to a 4
      point semiquantitative scale. Pre- and post-treatment US scores were compared and
      the sensitivity to change of GSUS and PDUS was estimated. Clinical response was
      assessed using the ACR paediatric (ACRp) response criteria. RESULTS: Seventeen
      patients (51.5%) underwent intra-articular corticosteroid injection (IACI) only,
      15 (45.5%) were given IACI and systemic medications, and 1 (3.0%) was started
      with systemic therapy alone. Both GSUS and PDUS scores improved significantly
      (p<0.0001) from baseline to follow-up. US revealed strong sensitivity to change
      with standardised response mean for GSUS and PDUS of 2.44 and 1.23, respectively.
      At the follow-up visit, 13/20 (65.0%) joints with residual US abnormalities were
      judged in remission on clinical grounds. Six/21 (28.6%) patients who were ACRp90
      responders did not display complete resolution of synovial abnormalities on US.
      CONCLUSIONS: US is a sensitive tool to assess therapeutic response in patients
      with JIA. Subclinical disease on US is common in joints with clinically-defined
      remission. An ACRp90 response may not be coupled with complete resolution of
      synovial abnormalities on US. Further studies are needed to establish the impact
      of US on therapeutic decision-making in JIA.

PMID- 29185967
TI  - Increased aortic stiffness in patients with fibromyalgia: results of a
      prospective study on carotid-femoral pulse wave velocity.

PMID- 29185966
TI  - The prevalence and clinical effect of immunogenicity of TNF-alpha blockers in
      patients with axial spondyloarthritis.
AB  - OBJECTIVES: To evaluate the prevalence of immunogenicity of TNF-alpha blockers in
      axial spondyloarthritis (SpA) patients and to assess the effect of immunogenicity
      on drug levels and clinical response. METHPDS: Patients with axial SpA treated
      with either infliximab (INF), adalimumab (ADA) or etanercept (ETN) were recruited
      to our observational cross-sectional study. Demographic and clinical data were
      collected and disease activity scores were assessed. Drug trough levels and anti
      drug antibodies were measured in serum samples and collected before the next
      administration. RESULTS: Thirty-nine patients with axial SpA with a mean age of
      46.3+/-12.7 (10 women) were recruited to the study (14 receiving INF, 16 ADA and
      9 ETN). Patients' mean therapy duration was 50.6 months (+/-46.4) and 6 (15%) of
      them were using MTX concomitantly with the TNF-alpha blockers. Anti-drug
      antibodies were found in 6 (15%) patients (4 with INF and 2 with ADA), all of
      which had undetectable drug level. No anti-drug antibodies were detected in
      patients treated with ETN. Immunogenicity was associated with higher BASDAI (Bath
      Ankylosing Spondylitis Disease Index), ASDAS-CRP (Ankylosing Spondylitis Disease
      Activity Score) and ASDAS-ESR. CONCLUSIONS: Axial SpA patients failure to respond
      to TNF-alpha blockers may be at least partially related to immunogenicity.
      Measurement of anti-drug antibodies and drug levels in these patients may assist
      in determining further treatment strategies.

PMID- 29185968
TI  - The performance of anti-cyclic citrullinated peptide assays in diagnosing
      rheumatoid arthritis: a systematic review and meta-analysis.
AB  - OBJECTIVES: We assessed the ability of anti-cyclic citrullinated peptide (CCP)
      tests to diagnose rheumatoid arthritis (RA), comparing the effect of manufacturer
      assay type, study design (single- and two-gated) and duration of disease (early
      vs. established). METHODS: We searched seven databases for relevant diagnostic
      studies containing data on CCP tests in known or suspected RA patients. We used a
      bivariate model to produce summary estimates for test sensitivity, specificity,
      and positive and negative likelihood ratios. Summary Receiver Operating
      Characteristic (sROC) curves were derived to compare early versus established RA.
      RESULTS: 83 studies were identified and included. For individual manufacturer
      tests there was considerable variation in both pooled sensitivity (range 67-83%)
      and specificity (range 90-96%) estimates. This heterogeneity was also observed
      when grouping studies into two-gated and single-gated designs. Study design and
      disease duration impacted on sensitivity, with single-gated study designs and
      early RA patients resulting in lower estimates than two-gated and established
      disease, respectively. CONCLUSIONS: This review highlights the large number of
      CCP tests that are now commercially available and the considerable variation in
      their diagnostic performance. This variation, although partly influenced in this
      analysis by the study design (single-gated vs. two-gated), seems to have
      different levels of impact depending on the manufacturers. The Thermo Fisher
      Scientific EliA and Inova Diagnostics Quanta Lite (CCP2) tests showed the least
      between-study variation in sensitivity and specificity suggesting they have the
      most consistent diagnostic performance overall.

PMID- 29185970
TI  - If Congress Won't Salvage Reinsurance, State Waivers May Offer a Workaround.
AB  - Shards of a bipartisan effort to stabilize the individual health insurance
      markets emerged. They focused mostly on resurrecting the ACA cost-reduction
      payments and giving states flexibility to come up with their own ideas, like
      reinsurance, for shoring up the troubled individual market.

PMID- 29185969
TI  - Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis.
AB  - OBJECTIVES: Atherosclerotic cardiovascular disease risk is increased in
      rheumatoid arthritis (RA). Wave reflection occurs at arterial branching points,
      which are particularly prone to atherosclerosis. We explored the relationship of
      wave reflection with atherosclerosis in RA. METHODS: One hundred and sixty three
      RA patients (110 white, 31 Asian, 17 black and 5 of mixed ancestry) without
      cardiovascular disease participated. Arterial stiffness, wave reflection,
      pressure pulsatility, plaque in the extracranial carotid artery tree and the mean
      of the left and right common carotid arteries intima-thickness were determined.
      Associations were identified in multivariable regression models. RESULTS: One SD
      increase in reflected wave pressure (OR (95% CI) = 2.54 (1.41-4.44), p=0.001),
      reflection magnitude (OR (95% CI) = 1.84 (1.17-2.89), p=0.008), central pulse
      pressure (OR (95% CI) = 1.89 (1.12-3.22), p=0.02) and peripheral pulse pressure
      (OR (95% CI) = 2.09 (1.23-3.57), p=0.007) were associated with plaque. The
      association of wave reflection with plaque was independent of arterial stiffness
      and pressure pulsatility, and was present in both hypertensive and normotensive
      RA patients. In receiver operator characteristic curve analysis, the optimal
      cutoff value for reflected wave pressure in predicting plaque presence was 25
      mmHg with a sensitivity, specificity, positive predictive value and negative
      predictive value of 45.2%, 89.3%, 78.6% and 66.2%, respectively; a reflected wave
      pressure of >25 mmHg was associated with plaque in univariate and adjusted
      analysis (p<0.0001 for both). Arterial function was not independently related to
      carotid intima-media thickness. CONCLUSIONS: Consideration and therapeutic
      targeting of wave reflection may improve cardiovascular disease prevention in RA.

PMID- 29185971
TI  - Biosimilars Shake Off Doubters, Go on a Roll.
AB  - Seven biosimilars have crossed the FDA-approval finish line. The FDA has largely
      held to the abbreviated pathway it laid out originally. The big change is that
      the rest of the world is starting to understand it. Approvals are based upon "the
      totality of evidence," "analytic similarity," and clinical performance with much
      less emphasis placed on phase 3 trials.

PMID- 29185972
TI  - Cigna's Eva Borden Champions 'The Stepchild': Behavioral Health.
AB  - The insurer's general manager of behavioral and EAP services wants to make mental
      health care more mainstream. Only 17% of American adults function with optimal
      mental health. "We talk about it as if it's them over there, but 83% of us have a
      need."

PMID- 29185973
TI  - Seeing It From Both Sides Now.
AB  - How the world looks depends on your point of view. Medical directors, some with
      experience as payers and providers, share their thoughts on prior authorization,
      value-based care, and quality measurement.

PMID- 29185974
TI  - Vox Medical Directorae: What I wish the Other Side Could See.
AB  - They are all physicians. They all want to take care of people. But the chief
      medical officers at health plans and provider organizations often see the world
      through different lenses. Here, chief medical officers from both sides of the
      divide share their views.

PMID- 29185975
TI  - For Physician Executive Posts, What's in a Name?
AB  - Medical directors have been around for a long time. Today, to reflect expanding
      duties, there's a bewildering array of other titles too.

PMID- 29185976
TI  - Moving On up in the C-Suite.
AB  - For these two medical directors, the next logical career step was CEO.

PMID- 29185977
TI  - Answering the Call of the Wild Creates A Different Kind of Medical Director.
AB  - The medical director of the National Park Service and Grand Teton National Park
      lives on the edge in places like the mountains of Wyoming and the battlefields in
      Iraq.

PMID- 29185978
TI  - Blazing the Trail from Volume to Value.

PMID- 29185979
TI  - With Direct Contracting Boeing Cuts Out the Middleman.
AB  - The aerospace giant has direct contracts with health care systems in four
      markets. Should insurers worry that other large employers will cut them out and
      start dealing directly with integrated delivery systems?

PMID- 29185980
TI  - Venture Capital Throws Dough That Could Fix Health Care Woe.
AB  - Some experts say that investors funding innovative startup companies can disrupt
      American health care, making it smarter and more efficient. Others warn that
      incentives must change if VC money is to make a real difference. It's a trend no
      one in health care can ignore.

PMID- 29185981
TI  - FDA Gives First-Ever Approval of Drug To Treat Chagas' Disease.
AB  - A partnership that includes two not-for-profit organizations beats out a company
      formerly led by "pharma bro" Martin Shkreli for the FDA's OK of benznidazole.

PMID- 29185982
TI  - Adrenergic regulation during acute hepatic infection with Entamoeba histolytica
      in the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB.
AB  - Oxidative stress and transcriptional pathways of nuclear factor erythroid 2
      related factor 2 (Nrf2) and nuclear factor kappa-B (NF-kappaB) are critically
      involved in the etiopathology of amebic liver abscess (ALA). In this work, we
      studied the relationship between the adrenergic nervous system and ALA in the
      hamster. ALA was visible at 12 h of infection. While 6-hydroxidopamine (6-OHDA)
      decreased infection, propranolol (beta-adrenergic blocker) treatment was
      associated with less extensive liver damage, and phentolamine treatment (alpha
      adrenergic blocker) significantly reduced ALA compared to 6-OHDA and propranolol.
      Serum enzymatic activities of alanine aminotransferase (ALT) and gamma-glutamyl
      transpeptidase (gamma-GTP) were increased at 12 h post-infection. Chemical
      denervation and alpha and beta-adrenergic blockers decreased ALT to normal
      levels, while 6-OHDA and propranolol showed a trend to decrease gamma-GTP but
      phentolamine significantly reduced gamma-GTP. Amebic infection increased oxidized
      glutathione (GSSG) and decreased both reduced glutathione (GSH) and the GSH/GSSG
      ratio. Propranolol and 6-OHDA showed a tendency to decrease GSSG. However, GSH,
      GSSG and GSH/GSSG returned to normal levels with phentolamine. Furthermore,
      amebic infection increased pNF-kappaB and interleukin-1beta (IL-1beta), and
      showed a tendency to decrease hemoxigenase-1 (HO-1), but not Nrf2. Chemical
      denervation showed a trend to decrease pNF-kappaB and IL-1beta, and neither Nrf2
      nor HO-1 increased significantly. In addition, NF-kappaB and IL-1beta were
      attenuated by propranolol and phentolamine treatments, although phentolamine
      showed significant overexpression of Nrf2 and HO-1. This suggests that the
      adrenergic system may be involved in oxidative stress and in modulation of the
      Nrf2 and NF-kappaB pathways during ALA development.

PMID- 29185985
TI  - Parallel Block Sequential Closed-Form Matting With Fan-Shaped Partitions.
AB  - Applying alpha matting to large images is a challenging task because of its
      computational complexity. This paper provides a divide and conquer strategy for
      performing closed-form matting. The matting problem, defined for an entire image,
      is broken down into systems of linear equations defined for very small blocks of
      the image. The sizes of the small systems are small enough for us to find
      solutions efficiently using a direct sparse linear equation system solver. The
      small systems are solved following a sequential order such that the alpha matte
      grows from a user scribble. With the block sequential application, matting is
      performed on fan-shaped partitions in parallel on multiple processing cores.
      Experiments on large test images as well as on standard benchmark test images
      show that the proposed parallel block sequential matting provides high quality
      alpha mattes with good scalability.

PMID- 29185983
TI  - NuMA recruits dynein activity to microtubule minus-ends at mitosis.
AB  - To build the spindle at mitosis, motors exert spatially regulated forces on
      microtubules. We know that dynein pulls on mammalian spindle microtubule minus
      ends, and this localized activity at ends is predicted to allow dynein to cluster
      microtubules into poles. How dynein becomes enriched at minus-ends is not known.
      Here, we use quantitative imaging and laser ablation to show that NuMA targets
      dynactin to minus-ends, localizing dynein activity there. NuMA is recruited to
      new minus-ends independently of dynein and more quickly than dynactin; both NuMA
      and dynactin display specific, steady-state binding at minus-ends. NuMA
      localization to minus-ends involves a C-terminal region outside NuMA's canonical
      microtubule-binding domain and is independent of minus-end binders gamma-TuRC,
      CAMSAP1, and KANSL1/3. Both NuMA's minus-end-binding and dynein-dynactin-binding
      modules are required to rescue focused, bipolar spindle organization. Thus, NuMA
      may serve as a mitosis-specific minus-end cargo adaptor, targeting dynein
      activity to minus-ends to cluster spindle microtubules into poles.

PMID- 29185986
TI  - Novel Integration of Frame Rate Up Conversion and HEVC Coding Based on Rate
      Distortion Optimization.
AB  - Frame rate up conversion (FRUC) can improve the visual quality by interpolating
      new intermediate frames. However, high frame rate videos by FRUC are confronted
      with more bitrate consumption or annoying artifacts of interpolated frames. In
      this paper, a novel integration framework of FRUC and high efficiency video
      coding (HEVC) is proposed based on rate-distortion optimization, and the
      interpolated frames can be reconstructed at encoder side with low bitrate cost
      and high visual quality. First, joint motion estimation (JME) algorithm is
      proposed to obtain robust motion vectors, which are shared between FRUC and video
      coding. What's more, JME is embedded into the coding loop and employs the
      original motion search strategy in HEVC coding. Then, the frame interpolation is
      formulated as a rate-distortion optimization problem, where both the coding
      bitrate consumption and visual quality are taken into account. Due to the absence
      of original frames, the distortion model for interpolated frames is established
      according to the motion vector reliability and coding quantization error.
      Experimental results demonstrate that the proposed framework can achieve 21% ~
      42% reduction in BDBR, when compared with the traditional methods of FRUC
      cascaded with coding.

PMID- 29185984
TI  - Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by
      dispersed amino acid patches in EZH2.
AB  - Polycomb repressive complex 2 (PRC2) is a key chromatin modifier responsible for
      methylation of lysine 27 in histone H3. PRC2 has been shown to interact with
      thousands of RNA species in vivo, but understanding the physiological function of
      RNA binding has been hampered by the lack of separation-of-function mutants.
      Here, we use comprehensive mutagenesis and hydrogen deuterium exchange mass
      spectrometry (HDX-MS) to identify critical residues for RNA interaction in PRC2
      core complexes from Homo sapiens and Chaetomium thermophilum, for which crystal
      structures are known. Preferential binding of G-quadruplex RNA is conserved,
      surprisingly using different protein elements. Key RNA-binding residues are
      spread out along the surface of EZH2, with other subunits including EED also
      contributing, and missense mutations of some of these residues have been found in
      cancer patients. The unusual nature of this protein-RNA interaction provides a
      paradigm for other epigenetic modifiers that bind RNA without canonical RNA
      binding motifs.

PMID- 29185987
TI  - Tropical Cyclone Intensity Estimation Using a Deep Convolutional Neural Network.
AB  - Tropical cyclone intensity estimation is a challenging task as it required domain
      knowledge while extracting features, significant pre-processing, various sets of
      parameters obtained from satellites, and human intervention for analysis. The
      inconsistency of results, significant pre-processing of data, complexity of the
      problem domain, and problems on generalizability are some of the issues related
      to intensity estimation. In this study, we design a deep convolutional neural
      network architecture for categorizing hurricanes based on intensity using
      graphics processing unit. Our model has achieved better accuracy and lower root
      mean-square error by just using satellite images than 'state-of-the-art'
      techniques. Visualizations of learned features at various layers and their
      deconvolutions are also presented for understanding the learning process.

PMID- 29185988
TI  - Saliency Detection Based on Multiscale Extrema of Local Perceptual Color
      Differences.
AB  - Visual saliency detection is a useful technique for predicting, which regions
      humans will tend to gaze upon in any given image. Over the last several decades,
      numerous algorithms for automatic saliency detection have been proposed and shown
      to work well on both synthetic and natural images. However, two key challenges
      remain largely unaddressed: 1) How to improve the relatively low predictive
      performance for images that contain large objects and 2) how to perform saliency
      detection on a wider variety of images from various categories without training.
      In this paper, we propose a new saliency detection algorithm that addresses these
      challenges. Our model first detects potentially salient regions based on
      multiscale extrema of local perceived color differences measured in the CIELAB
      color space. These extrema are highly effective for estimating the locations,
      sizes, and saliency levels of candidate regions. The local saliency candidates
      are further refined via two global extrema-based features, and then a Gaussian
      mixture is used to generate the final saliency map. Experimental validation on
      the extensive CAT2000 data set demonstrates that our proposed method either
      outperforms or is highly competitive with prior approaches, and can perform well
      across different categories and object sizes, while remaining training-free.

PMID- 29185989
TI  - Blind Stereoscopic Video Quality Assessment: From Depth Perception to Overall
      Experience.
AB  - Stereoscopic video quality assessment (SVQA) is a challenging problem. It has not
      been well investigated on how to measure depth perception quality independently
      under different distortion categories and degrees, especially exploit the depth
      perception to assist the overall quality assessment of 3D videos. In this paper,
      we propose a new depth perception quality metric (DPQM) and verify that it
      outperforms existing metrics on our published 3D video extension of High
      Efficiency Video Coding (3D-HEVC) video database. Furthermore, we validate its
      effectiveness by applying the crucial part of the DPQM to a novel blind
      stereoscopic video quality evaluator (BSVQE) for overall 3D video quality
      assessment. In the DPQM, we introduce the feature of auto-regressive prediction
      based disparity entropy (ARDE) measurement and the feature of energy weighted
      video content measurement, which are inspired by the free-energy principle and
      the binocular vision mechanism. In the BSVQE, the binocular summation and
      difference operations are integrated together with the fusion natural scene
      statistic measurement and the ARDE measurement to reveal the key influence from
      texture and disparity. Experimental results on three stereoscopic video databases
      demonstrate that our method outperforms state-of-the-art SVQA algorithms for both
      symmetrically and asymmetrically distorted stereoscopic video pairs of various
      distortion types.

PMID- 29185990
TI  - Obstacles in using a computer screen for steady-state visually evoked potential
      stimulation.
AB  - In brain computer interface (BCI) applications, the use of steady-state visually
      evoked potentials (SSVEPs) is common. Therefore, a visual stimulation with a
      constant repetition frequency is necessary. However, using a computer monitor,
      the set of frequencies that can be used is restricted by the refresh rate of the
      screen. Frequencies that are not an integer divisor of the refresh rate cannot be
      displayed correctly. Furthermore, the programming language the stimulation
      software is written in and the operating system influence the actually generated
      and presented frequencies. The aim of this paper is to identify the main
      challenges in generating SSVEP stimulation using a computer screen with and
      without using DirectX in Windows-based PC systems and to provide solutions for
      these issues.

PMID- 29185991
TI  - Pharmacokinetics of favipiravir during continuous venovenous haemofiltration in a
      critically ill patient with influenza.
AB  - Favipiravir is a novel antiviral drug approved for influenza treatment in Japan.
      Little is known about favipiravir pharmacokinetics in critically ill patients.
      Here, we report a patient with influenza treated with favipiravir and undergoing
      continuous venovenous haemofiltration (CVVH) on the Intensive Care Unit of a
      tertiary hospital in the Netherlands. Pharmacokinetic analyses showed increased
      clearance and decreased plasma levels compared to healthy volunteers. CVVH has no
      clinically relevant contribution to total clearance. Despite susceptibility to
      favipiravir, the influenza virus was not cleared. A multi-disciplinary approach
      is needed to ensure optimal favipiravir treatment in critically ill patients.

PMID- 29185992
TI  - Fixed forced detection for fast SPECT Monte-Carlo simulation.
AB  - Monte-Carlo simulations of SPECT images are notoriously slow to converge due to
      the large ratio between the number of photons emitted and detected in the
      collimator. This work proposes a method to accelerate the simulations based on
      fixed forced detection (FFD) combined with an analytical response of the
      detector. FFD is based on a Monte-Carlo simulation but forces the detection of a
      photon in each detector pixel weighted by the probability of emission (or
      scattering) and transmission to this pixel. The method was evaluated with
      numerical phantoms and on patient images. We obtained differences with analog
      Monte Carlo lower than the statistical uncertainty. The overall computing time
      gain can reach up to five orders of magnitude. Source code and examples are
      available in the Gate V8.0 release.

PMID- 29185993
TI  - Detection of protease activity by fluorescent protein FRET sensors: from computer
      simulation to live cells.
AB  - Forster resonance energy transfer (FRET) sensors are widely used for the
      detection of protease activity in vitro and in vivo. Usually they consist of a
      FRET pair connected with a polypeptide linker containing a specific cleavage site
      for the relevant protease. Use of the fluorescent proteins as components of the
      FRET pair allows genetic encoding of such sensors and solves the problem of their
      delivery into live cells and animals. There are several ways to improve the
      properties of such sensors, mainly to increase FRET efficiency and therefore the
      dynamic range. One of the ways to achieve this is to use a non-fluorescent
      chromoprotein as an acceptor. Molecular dynamic simulations may assist in the
      construction of linker structures connecting donor and acceptor molecules.
      Estimation of the orientation factor kappa 2 can be obtained by methods based on
      quantum theory and combined quantum mechanics/molecular mechanics approaches. The
      linker can be structured by hydrophobic interactions, bringing it into a closed
      conformation that shortens the distance between donor and acceptor and,
      consequently, increases FRET efficiency. We analyzed the effects of different
      linker structures on the detection of caspase-3 activity using a non-fluorescent
      acceptor. Also we have constructed the Tb3+- TagRFP sensor in which a complex of
      the terbium ion and terbium-binding peptide is used as a donor. This allowed us
      to use the unique property of lanthanide ions-fluorescence lifetime up to
      milliseconds-to perform measurements with time delay and exclude the nanosecond
      order fluorescence. Using our systems as a starting point, by changing the
      recognition site in the linker it is possible to perform imaging of different
      protease activity in vitro or in vivo.

PMID- 29185994
TI  - Linear and nonlinear features of fetal heart rate on the assessment of fetal
      development in the course of pregnancy and the impact of fetal gender.
AB  - OBJECTIVE: This work aims to investigate the impact of gestational age and fetal
      gender on fetal heart rate (FHR) tracings. APPROACH: Different linear and
      nonlinear parameters indicating correlation or complexity were used to study the
      influence of fetal age and gender on FHR tracings. The signals were recorded from
      99 normal pregnant women in a singleton pregnancy at gestational ages from 28 to
      40 weeks, before the onset of labor. There were 56 female fetuses and 43 male.
      MAIN RESULTS: Analysis of FHR shows that the means as well as measures of
      irregularity of FHR, such as approximate entropy and algorithmic complexity,
      decrease as gestation progresses. There were also indications that mutual
      information and multiscale entropy were lower in male fetuses in early pregnancy.
      SIGNIFICANCE: Fetal age and gender seem to influence FHR tracings. Taking this
      into consideration would improve the interpretation of FHR monitoring.

PMID- 29185995
TI  - Noise creates polarization artefacts.
AB  - The accuracy of calculations of both the degree and angle of polarization depend
      strongly on the noise in the measurements used. The noise in the measurements
      recorded by both camera based systems and spectrometers can lead to significant
      artefacts and incorrect conclusions about high degrees of polarization when in
      fact none exist. Three approaches are taken in this work: firstly, the absolute
      error introduced as a function of the signal to noise ratio for polarization
      measurements is quantified in detail. An important finding here is the reason for
      why several studies incorrectly suggest that black (low reflectivity) objects are
      highly polarized. The high degree of polarization is only an artefact of the
      noise in the calculation. Secondly, several simple steps to avoid such errors are
      suggested. Thirdly, if these points can not be followed, two methods are
      presented for mitigating the effects of noise: a maximum likelihood estimation
      method and a new denoising algorithm to best calculate the degree of polarization
      of natural polarization information.

PMID- 29185996
TI  - Electrical conductivity of In<sub>2</sub>O<sub>3</sub> and
      Ga<sub>2</sub>O<sub>3</sub> after low temperature ion irradiation; implications
      for instrinsic defect formation and charge neutrality level.
AB  - The evolution of sheet resistance of n-type In2O3 and Ga2O3 exposed to
      bombardment with MeV&#13; 12C and 28Si ions at 35 K is studied in situ. While the
      sheet resistance of Ga2O3 increased by&#13; more than 8 orders of magnitude as a
      result of ion irradiation, In2O3 showed a more complex defect&#13; evolution and
      became more conductive when irradiated at the highest doses. Heating up to
      room&#13; temperature reduced the sheet resistivity somewhat, but Ga2O3 remained
      highly resistive, while&#13; In2O3 showed a lower resistance than as deposited
      samples. Thermal admittance spectroscopy and&#13; deep level transient
      spectroscopy did not reveal new defect levels for irradiation up to 2 1012&#13;
      cm2. A model where larger defect complexes preferentially produce donor like
      defects in In2O3&#13; is proposed, and may reveal a microscopic view of a charge
      neutrality level within the conduction&#13; band, as previously proposed.

PMID- 29185997
TI  - Site occupancy, composition and magnetic structure dependencies of martensitic
      transformation in Mn2Ni1 + x Sn1-x.
AB  - A delicate balance between various factors such as site occupancy, composition
      and magnetic ordering seems to affect the stability of the martensitic phase in
      [Formula: see text] [Formula: see text] [Formula: see text]. Using first
      principles DFT calculations, we explore the impacts of each one of these factors
      on the martensitic stability of this system. Our results on total energies,
      magnetic moments and electronic structures upon changes in the composition, the
      magnetic configurations and the site occupancies show that the occupancies at the
      4d sites in the inverse Heusler crystal structure play the most crucial role. The
      presence of Mn at the 4d sites originally occupied by Sn and its interaction with
      the Mn atoms at other sites decide the stability of the martensitic phases. This
      explains the discrepancy between the experiments and earlier DFT calculations
      regarding phase stability in [Formula: see text]NiSn. Our results qualitatively
      explain the trends observed experimentally with regard to martensitic phase
      stability and the magnetisations in Ni-excess, Sn-deficient [Formula: see
      text]NiSn system.

PMID- 29185998
TI  - Temperature dependent structural evolution in liquid Ag50Ga50 alloy.
AB  - The temperature dependence of atomic structural evolution in liquid Ag50Ga50
      alloy has been studied using an in situ high energy x-ray diffraction (XRD)
      experiment combined with first-principles molecular dynamics (FPMD) simulations.
      The experimental data show a reversible structural crossover at the temperature
      of about 1050 K. Changes in both electrical resistivity and absolute
      thermoelectric power at about 1100 K strongly support the XRD results.
      Additionally, FPMD simulations reveal the abnormal temperature dependent behavior
      of partial coordination number and atomic diffusivity at about 1200 K,
      elucidating that the partition experimentally observed changes in structure and
      properties could be linked with the repartition between Ag and Ga atoms in the
      liquid at around 1050-1200 K. This finding will trigger more studies on the
      structural evolution of noble-polyvalent metals in particular and metallic
      liquids in general.

PMID- 29185999
TI  - Demagnetizing fields in all-optical switching.
AB  - A model of demagnetizing fields and micromagnetic simulations are applied to
      examine the evolution of a demagnetized cylinder. In addition to three expected
      final magnetic structures, a fourth switched state is obtained over a range of
      magnetic energy densities. The switched state is absent when demagnetizing fields
      are neglected. The connection to all-optical switching of materials with
      perpendicular magnetic anisotropy is discussed.

PMID- 29186000
TI  - Effect of Pt and Au current collector in LiMn2O4 thin film for micro-batteries.
AB  - The crystal orientation and morphology of sputtered LiMn2O4 thin films is
      strongly affected by the current collector. By substituting Pt with Au, it is
      possible to observe in the x-ray diffraction pattern of LiMn2O4 a change in the
      preferential orientation of the grains from (111) to (400). In addition, LiMn2O4
      thin films deposited on Au show a higher porosity than films deposited on Pt.
      These structural differences cause an improvement in the electrochemical
      performances of the thin films deposited on Au, with up to 50% more specific
      charge. Aqueous cells using thin film based on LiMn2O4 sputtered on Au or Pt as
      the cathode electrode present a similar retention of specific charge, delivering
      85% and 100%, respectively, of the initial values after 100 cycles. The critical
      role of the nature of the substrate used in the morphology and electrochemical
      behaviour observed could permit the exploration of similar effects for other
      lithium intercalation electrodes.

PMID- 29186001
TI  - Dynamic electron-ion collisions and nuclear quantum effects in quantum simulation
      of warm dense matter.
AB  - The structural, thermodynamic and transport properties of warm dense matter (WDM)
      are crucial to the fields of astrophysics and planet science, as well as inertial
      confinement fusion. WDM refers to the states of matter in a regime of temperature
      and density between cold condensed matter and hot ideal plasmas, where the
      density is from near-solid up to ten times solid density, and the temperature
      between 0.1 and 100 eV. In the WDM regime, matter exhibits moderately or strongly
      coupled, partially degenerate properties. Therefore, the methods used to deal
      with condensed matter and isolated atoms need to be properly validated for WDM.
      It is therefore a big challenge to understand WDM within a unified theoretical
      description with reliable accuracy. Here, we review the progress in the
      theoretical study of WDM with state-of-the-art simulations, i.e. quantum Langevin
      molecular dynamics and first principles path integral molecular dynamics. The
      related applications for WDM are also included.

PMID- 29186002
TI  - Spin Hall magnetoresistance in the non-collinear ferrimagnet GdIG close to the
      compensation temperature.
AB  - We investigate the spin Hall magnetoresistance (SMR) in a gadolinium iron garnet
      (GdIG)/platinum (Pt) heterostructure by angular dependent magnetoresistance
      measurements. The magnetic structure of the ferromagnetic insulator GdIG is non
      collinear near the compensation temperature, while it is collinear far from the
      compensation temperature. In the collinear regime, the SMR signal in GdIG is
      consistent with the usual [Formula: see text] relation well established in the
      collinear magnet yttrium iron garnet, with [Formula: see text] the angle between
      magnetization and spin Hall spin polarization direction. In the non-collinear
      regime, both an SMR signal with inverted sign and a more complex angular
      dependence with four maxima are observed within one sweep cycle. The number of
      maxima as well as the relative strength of different maxima depend strongly on
      temperature and field strength. Our results evidence a complex SMR behavior in
      the non-collinear magnetic regime that goes beyond the conventional formalism
      developed for collinear magnetic structures.

PMID- 29186003
TI  - Magnetic behavior of metastable Fe films grown on Ir(1 1 1).
AB  - We investigated the growth of ultra-thin Fe films on Ir(1 1 1) by means of in
      situ low energy electron diffraction and spin-resolved photoemission techniques.
      We observe a (1  *  1) diffraction pattern, characteristic of the fcc substrate,
      below four monolayers (ML). Then, a complex superstructure starts to develop,
      compatible with the formation of bcc-like Fe domains aligned with the substrate
      according to the Kourdjumov-Sachs orientation relationships. The analysis of the
      diffraction patterns reveals a progressive evolution towards a fully relaxed bcc
      lattice, characteristic of bulk Fe. Both photoemission (filled states) and
      inverse photoemission (empty states) results show characteristic features related
      to the contribution of the Fe layer, evolving towards those observed on the Fe (1
      1 0) bcc surface. Spin resolution allows to detect a spectral polarization above
      4 ML, corresponding to the formation of bcc Fe, which gradually increases
      indicating the formation of an in-plane magnetized ferromagnetic layer in thick
      films. No in-plane net magnetization is detected in thinner films, independent of
      the sample temperature down to 30 K. Following recent investigations on the
      Fe/Ir(1 1 1) system with microscopy techniques, we link this observation to the
      stabilization of a non collinear spin structure yielding an overall nil
      magnetization.

PMID- 29186004
TI  - Pressure dependence of Ce valence in CeRhIn<sub>5</sub>.
AB  - We have studied the Ce valence as a function of pressure in CeRhIn<sub>5</sub> at
      300 K and at 22 K using x-ray absorption spectroscopy in partial fluorescent
      yield mode. At room temperature, we found no detectable change in Ce valence
      greater than 0.01 up to a pressure of 5.5 GPa. At 22 K, the valence remains
      robust against pressure below 6GPa, in contrast to the predicted valence
      crossover at P=2.35 GPa. This work yields an upper limit for the change in Ce
      valence and suggests that the critical valence fluctuation scenario, in its
      current form, is unlikely.

PMID- 29186005
TI  - Intense blue upconversion emission and intrinsic optical bistability in
      Tm3+/Yb3+/Zn2+ tridoped YVO4 phosphors.
AB  - Tm3+/Yb3+/Zn2+:yttrium metavanadate (YVO4) phosphors prepared through chemical
      coprecipitation and the solid state reaction method have been structurally
      characterized by an x-ray diffraction (XRD) study. Photoluminescence study of the
      developed phosphors under ultraviolet (UV) and near infrared (NIR) excitation has
      been performed. The excitation spectrum of the tetragonal zircon type YVO4
      phosphors corresponding to the emission at ~476 nm exhibits a broad excitation
      peak in the 250-350 nm region, which is due to charge distribution in the
      [Formula: see text] group. Under 980 nm CW diode laser excitation, enhancements
      of about ~3000 times and ~40 times have been observed for the blue band in the
      tridoped Tm3+Yb3+Zn2+:YVO4 phosphors compared to those of the Tm3+:YVO4 singly
      and Tm3+/Yb3+:YVO4 codoped phosphors, respectively. A downconversion (DC)
      emission study shows an enhancement of about ~50 times for the blue band in the
      tridoped phosphors compared to that of the singly doped phosphors. Optical
      bistability (OB) behavior of the developed phosphors has been also investigated
      upon 980 nm excitation. The calculated Commission Internationale de l'Eclairage
      (CIE) color coordinates lie in the blue region with 96.5% color purity under 980
      nm excitation, having a color temperature of ~3400 K. Our observations show that
      the developed phosphors may be suitably used in dual mode luminescence
      spectroscopy, display devices, and UV LED chips.

PMID- 29186006
TI  - Field-tuned superconductor-insulator transitions and Hall resistance in thin
      polycrystalline MoN films.
AB  - We report on the superconductor-insulator transitions (SITs) of disordered
      molybdenum nitride (MoN) thin films on (1 0 0) MgO substrates as a function of
      the film thickness and magnetic fields. The T c of the superconducting MoN films,
      which exhibit a sharp superconducting transition, monotonically decreases as the
      normal state R sq increases with a decreasing film thickness. For several films
      with different thicknesses, we estimate the critical field H c and the product
      znu  ?  0.6 of the dynamical exponent z and the correlation length exponent nu
      using a finite scaling analysis. The value of this product can be explained by
      the (2  +  1) XY model. We found that the Hall resistance DeltaR xy (H) is
      maximized when the magnetic field satisfies H HP(T) [Formula: see text] |1  - 
      T/T C0| in the superconducting state and also in the normal states owning to the
      superconducting fluctuation corresponding to the ghost critical magnetic field.
      We measured the Hall conductivity deltasigma xy (H)  =  sigma xy (H)  - 
      [Formula: see text] and fit the Gaussian approximation theory for deltasigma xy
      (H) to the experimental data. Agreement between the data and the theory beyond H
      c suggests the survival of the Cooper pair in the insulating region of the SIT.

PMID- 29186007
TI  - Anatomically realistic ultrasound phantoms using gel wax with 3D printed moulds.
AB  - Here we describe methods for creating tissue-mimicking ultrasound phantoms based
      on patient anatomy using a soft material called gel wax. To recreate acoustically
      realistic tissue properties, two additives to gel wax were considered: paraffin
      wax to increase acoustic attenuation, and solid glass spheres to increase
      backscattering. The frequency dependence of ultrasound attenuation was well
      described with a power law over the measured range of 3-10 MHz. With the addition
      of paraffin wax in concentrations of 0 to 8 w/w%, attenuation varied from 0.72 to
      2.91 dB cm-1 at 3 MHz and from 6.84 to 26.63 dB cm-1 at 10 MHz. With solid glass
      sphere concentrations in the range of 0.025-0.9 w/w%, acoustic backscattering
      consistent with a wide range of ultrasonic appearances was achieved. Native gel
      wax maintained its integrity during compressive deformations up to 60%; its
      Young's modulus was 17.4  +/-  1.4 kPa. The gel wax with additives was shaped by
      melting and pouring it into 3D printed moulds. Three different phantoms were
      constructed: a nerve and vessel phantom for peripheral nerve blocks, a heart
      atrium phantom, and a placental phantom for minimally-invasive fetal
      interventions. In the first, nerves and vessels were represented as hyperechoic
      and hypoechoic tubular structures, respectively, in a homogeneous background. The
      second phantom comprised atria derived from an MRI scan of a patient with an
      intervening septum and adjoining vena cavae. The third comprised the chorionic
      surface of a placenta with superficial fetal vessels derived from an image of a
      post-partum human placenta. Gel wax is a material with widely tuneable ultrasound
      properties and mechanical characteristics that are well suited for creating
      patient-specific ultrasound phantoms in several clinical disciplines.

PMID- 29186008
TI  - PET attenuation correction for flexible MRI surface coils in hybrid PET/MRI using
      a 3D depth camera.
AB  - PET attenuation correction for flexible MRI radio frequency surface coils in
      hybrid PET/MRI is still a challenging task, as position and shape of these coils
      conform to large inter-patient variabilities. The purpose of this feasibility
      study is to develop a novel method for the incorporation of attenuation
      information about flexible surface coils in PET reconstruction using the
      Microsoft Kinect V2 depth camera. The depth information is used to determine a
      dense point cloud of the coil's surface representing the shape of the coil. From
      a CT template-acquired once in advance-surface information of the coil is
      extracted likewise and converted into a point cloud. The two point clouds are
      then registered using a combination of an iterative-closest-point (ICP) method
      and a partially rigid registration step. Using the transformation derived through
      the point clouds, the CT template is warped and thereby adapted to the PET/MRI
      scan setup. The transformed CT template is converted into an attenuation map from
      Hounsfield units into linear attenuation coefficients. The resulting fitted
      attenuation map is then integrated into the MRI-based patient-specific DIXON
      based attenuation map of the actual PET/MRI scan. A reconstruction of phantom PET
      data acquired with the coil present in the field-of-view (FoV), but without the
      corresponding coil attenuation map, shows large artifacts in regions close to the
      coil. The overall count loss is determined to be around 13% compared to a PET
      scan without the coil present in the FoV. A reconstruction using the new MU-map
      resulted in strongly reduced artifacts as well as increased overall PET
      intensities with a remaining relative difference of about 1% to a PET scan
      without the coil in the FoV.

PMID- 29186009
TI  - (Tl, Au)/Si(1 1 1)[Formula: see text] 2D compound: an ordered array of identical
      Au clusters embedded in Tl matrix.
AB  - Formation of the highly-ordered [Formula: see text]-periodicity 2D compound has
      been detected in the (Tl, Au)/Si(1 1 1) system as a result of Au deposition onto
      the Tl/Si(1 1 1) surface, its composition, structure and electronic properties
      have been characterized using scanning tunneling microscopy, angle-resolved
      photoelectron spectroscopy and density-functional-theory calculations. On the
      basis of these data, the structural model of the Tl-Au compound has been
      proposed, which adopts 12 Tl atoms and 10 Au atoms (in total, 22 atoms) per
      [Formula: see text] unit cell, i.e.  ~1.71 ML of Tl and  ~1.43 ML of Au (in
      total, ~3.14 ML). Qualitatively, the model can be visualized as consisting of
      truncated-pyramid-like Au clusters with a Tl atom on top, while the other Tl
      atoms form a double layer around the Au clusters. The (Tl, Au)/Si(1 1 1)[Formula:
      see text] compound has been found to exhibit pronounced metallic properties at
      least down to temperatures as low as  ~25 K, which makes it a promising object
      for studying electrical transport phenomena in the 2D metallic systems.

PMID- 29186010
TI  - Unidirectional lateral nanowire formation during the epitaxial growth of GaAsBi
      on vicinal substrates.
AB  - We report on enhanced control of the growth of lateral GaAs nanowires (NWs)
      embedded in epitaxial (100) GaAsBi thin films enabled by the use of vicinal
      substrates and the growth-condition dependent role of Bi as a surfactant.
      Enhanced step-flow growth is achieved through the use of vicinal substrates and
      yields unidirectional nanowire growth. The addition of Bi during GaAsBi growth
      enhances Ga adatom diffusion anisotropy and modifies incorporation rates at steps
      in comparison to GaAs growth yielding lower density but longer NWs. The NWs grown
      on vicinal substrates grew unidirectionally towards the misorientation direction
      when Bi was present. The III/V flux ratio significantly impacts the size, shape
      and density of the resulting NWs. These results suggest that utilizing growth
      conditions which enhance step-flow growth enable enhanced control of lateral
      nanostructures.

PMID- 29186011
TI  - Using biomaterials to promote pro-regenerative glial phenotypes after nervous
      system injuries.
AB  - Trauma to either the central or peripheral nervous system (PNS) often leads to
      significant loss of function and disability in patients. This high rate of long
      term disability is due to the overall limited regenerative potential of nervous
      tissue, even though the PNS has more regenerative potential than the central
      nervous system (CNS). The supporting glial cells in the periphery, Schwann cells,
      are part of the reason for the improved recovery observed in the PNS. In the CNS,
      the glial populations, astrocytes and oligodendrocytes (OLs), do not have as much
      potential to promote regeneration and are at times inhibitory to neuronal growth.
      In particular, the inhibitory roles astrocytes play following trauma has led to a
      historical focus on neurons and OLs instead of astrocytes. Recently, this focus
      has shifted as new, regenerative astrocyte phenotypes have been described. From
      these observations, glial cells clearly play critical roles in native recovery
      pathways in both the CNS and PNS. This makes the ability to manipulate both
      transplanted and native glial cell phenotypes a potentially successful strategy
      to improve nerve injury outcomes. This review focuses on factors that cause glial
      cells to adopt repair phenotypes and biomaterials that manipulate and/or harness
      these glial phenotypes.

PMID- 29186012
TI  - Transparent Electrode Based on Silver Nanowires and Polyimide for Film Heater and
      Flexible Solar Cell.
AB  - Transparent, conductive, and flexible Ag nanowire (NW)-polyimide (PI) composite
      films were fabricated by a facile solution method. Well-dispersed Ag NWs result
      in percolation networks on the PI supporting layer. A series of films with
      transmittance values of 53-80% and sheet resistances of 2.8-16.5 Omega/sq were
      investigated. To further verify the practicability of the Ag NWs-PI film in
      optoelectronic devices, we utilized it in a film heater and a flexible solar
      cell. The film heater was able to generate a temperature of 58  degrees C at a
      driving voltage of 3.5 V within 20 s, indicating its potential application in
      heating devices that require low power consumption and fast response. The
      flexible solar cell based on the composite film with a transmittance value of 71%
      presented a power conversion efficiency of 3.53%. These successful applications
      proved that the fabricated Ag NWs-PI composite film is a good candidate for
      application in flexible optoelectronic devices.

PMID- 29186014
TI  - Comprehensive Detection of Gas Plumes from Multibeam Water Column Images with
      Minimisation of Noise Interferences.
AB  - Multibeam echosounder systems (MBES) can record backscatter strengths of gas
      plumes in the water column (WC) images that may be an indicator of possible
      occurrence of gas at certain depths. Manual or automatic detection is generally
      adopted in finding gas plumes, but frequently results in low efficiency and high
      false detection rates because of WC images that are polluted by noise. To improve
      the efficiency and reliability of the detection, a comprehensive detection method
      is proposed in this paper. In the proposed method, the characteristics of WC
      background noise are first analyzed and given. Then, the mean standard deviation
      threshold segmentations are respectively used for the denoising of time-angle and
      depth-angle images, an intersection operation is performed for the two segmented
      images to further weaken noise in the WC data, and the gas plumes in the WC data
      are detected from the intersection image by the morphological constraint. The
      proposed method was tested by conducting shallow-water and deepwater experiments.
      In these experiments, the detections were conducted automatically and higher
      correct detection rates than the traditional methods were achieved. The
      performance of the proposed method is analyzed and discussed.

PMID- 29186013
TI  - Improving the Accessibility and Efficiency of Point-of-Care Diagnostics Services
      in Low- and Middle-Income Countries: Lean and Agile Supply Chain Management.
AB  - Access to point-of-care (POC) diagnostics services is essential for ensuring
      rapid disease diagnosis, management, control, and surveillance. POC testing
      services can improve access to healthcare especially where healthcare
      infrastructure is weak and access to quality and timely medical care is a
      challenge. Improving the accessibility and efficiency of POC diagnostics
      services, particularly in resource-limited settings, may be a promising route to
      improving healthcare outcomes. In this review, the accessibility of POC testing
      is defined as the distance/proximity to the nearest healthcare facility for POC
      diagnostics service. This review provides an overview of the impact of POC
      diagnostics on healthcare outcomes in low- and middle-income countries (LMICs)
      and factors contributing to the accessibility of POC testing services in LMICs,
      focusing on characteristics of the supply chain management and quality systems
      management, characteristics of the geographical location, health infrastructure,
      and an enabling policy framework for POC diagnostics services. Barriers and
      challenges related to the accessibility of POC diagnostics in LMICs were also
      discussed. Bearing in mind the reported barriers and challenges as well as the
      disease epidemiology in LMICs, we propose a lean and agile supply chain
      management framework for improving the accessibility and efficiency of POC
      diagnostics services in these settings.

PMID- 29186015
TI  - Establishing Genotype-to-Phenotype Relationships in Bacteria Causing Hospital
      Acquired Pneumonia: A Prelude to the Application of Clinical Metagenomics.
AB  - Clinical metagenomics (CMg), referred to as the application of next-generation
      sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of
      hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and
      antibiotic resistance genes (ARGs), thereby providing the information required
      for the optimization of the antibiotic regimen. Hence, provided that CMg would be
      faster than conventional culture, the probabilistic regimen used in HAP could be
      tailored faster, which should lead to an expected decrease of mortality and
      morbidity. While the inference of the antibiotic susceptibility testing from
      metagenomic or even genomic data is challenging, a limited number of antibiotics
      are used in the probabilistic regimen of HAP (namely beta-lactams,
      aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones).
      Accordingly, based on the perspective of applying CMg to the early diagnostic of
      HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of
      the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa,
      Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus)
      for the prediction of susceptibility to the antibiotic families advocated in the
      probabilistic regimen of HAP.

PMID- 29186016
TI  - The Moderating Effects of Students' Personality Traits on Pro-Environmental
      Behavioral Intentions in Response to Climate Change.
AB  - This study developed a model that examined the relationship between undergraduate
      students' beliefs, norms and pro-environment behavioral intentions in the context
      of global climate change (GCC). The model was further evaluated to determine
      whether latent variables, such as sustainability value, environmental concern,
      social norms, perceived risk, pro-environmental attitude, as defined by the
      theory of planned behavior and value-belief-norm theory, significantly influenced
      students' intentions towards pro-environmental behavior. The research model was
      empirically tested using data collected form 275 undergraduate students.
      Empirical results found support for four interaction effects of personality
      traits and the related latent variables of environmental attitude, including
      sustainability value, social norms, environmental concern and perceived risk. The
      impact of undergraduate students' environmental attitudes was moderated by
      personality traits. The findings of this research offer policy makers and
      enterprises better understandings of undergraduate students' attitudes and
      behavioral intentions towards GCC and promote the visibility of this issue.

PMID- 29186017
TI  - Effect of Food Residues in Biofilm Formation on Stainless Steel and Polystyrene
      Surfaces by Salmonella enterica Strains Isolated from Poultry Houses.
AB  - Salmonella spp. is a major food-borne pathogen around the world. The ability of
      Salmonella to produce biofilm is one of the main obstacles in reducing the
      prevalence of these bacteria in the food chain. Most of Salmonella biofilm
      studies found in the literature used laboratory growth media. However, in the
      food chain, food residues are the principal source of nutrients of Salmonella. In
      this study, the biofilm formation, morphotype, and motility of 13 Salmonella
      strains belonging to three different subspecies and isolated from poultry houses
      was evaluated. To simulate food chain conditions, four different growth media
      (Tryptic Soy Broth at 1/20 dilution, milk at 1/20 dilution, tomato juice, and
      chicken meat juice), two different surfaces (stainless steel and polystyrene) and
      two temperatures (6  degrees C and 22  degrees C) were used to evaluate the
      biofilm formation. The morphotype, motility, and biofilm formation of Salmonella
      was temperature-dependent. Biofilm formation was significantly higher with 1/20
      Tryptic Soy Broth in all the surfaces and temperatures tested, in comparison with
      the other growth media. The laboratory growth medium 1/20 Tryptic Soy Broth
      enhanced biofilm formation in Salmonella. This could explain the great
      differences in biofilm formation found between this growth medium and food
      residues. However, Salmonella strains were able to produce biofilm on the
      presence of food residues in all the conditions tested. Therefore, the Salmonella
      strain can use food residues to produce biofilm on common surfaces of the food
      chain. More studies combining more strains and food residues are necessary to
      fully understand the mechanism used by Salmonella to produce biofilm on the
      presence of these sources of nutrients.

PMID- 29186018
TI  - Campylobacter in Broiler Chicken and Broiler Meat in Sri Lanka: Influence of Semi
      Automated vs. Wet Market Processing on Campylobacter Contamination of Broiler
      Neck Skin Samples.
AB  - Broiler meat can become contaminated with Campylobacter of intestinal origin
      during processing. The present study aimed to identify the prevalence of
      Campylobacter in broiler flocks and meat contamination at retail shops, and
      determine the influence of semi-automated and wet market processing on
      Campylobacter contamination of neck skin samples. Samples were collected from
      semi-automated plants (n = 102) and wet markets (n = 25). From each batch of
      broilers, pooled caecal samples and neck skin samples were tested for
      Campylobacter. Broiler meat purchased from retail outlets (n = 37) was also
      tested. The prevalence of Campylobacter colonized broiler flocks was 67%. The
      contamination of meat at retail was 59%. Both semi-automated and wet market
      processing resulted to contaminate the broiler neck skins to the levels of 27.4%
      and 48%, respectively. When Campylobacter-free broiler flocks were processed in
      semi-automated facilities 15% (5/33) of neck skin samples became contaminated by
      the end of processing whereas 25% (2/8) became contaminated after wet market
      processing. Characterization of isolates revealed a higher proportion of C. coli
      compared to C. jejuni. Higher proportions of isolates were resistant to important
      antimicrobials. This study shows the importance of Campylobacter in poultry
      industry in Sri Lanka and the need for controlling antimicrobial resistance.

PMID- 29186019
TI  - Bioaccumulation and Toxicity of Carbon Nanoparticles Suspension Injection in
      Intravenously Exposed Mice.
AB  - Carbon nanoparticles suspension injection (CNSI) has been widely used in tumor
      drainage lymph node mapping, and its new applications in drug delivery,
      photothermal therapy, and so on have been extensively investigated. To develop
      new clinical applications, the toxicity of CNSI after intravenous exposure should
      be thoroughly investigated to ensure its safe use. Herein, we studied the
      bioaccumulation of CNSI in reticuloendothelial system (RES) organs and the
      corresponding toxicity to mice. After the intravenous injection of CNSI, no
      abnormal behavior of mice was observed during the 28-day observation period. The
      body weight increases were similar among the exposed groups and the control
      group. The parameters of hematology and serum biochemistry remained nearly
      unchanged, with very few of them showing significant changes. The low toxicity of
      CNSI was also reflected by the unchanged histopathological characteristics of
      these organs. The injection of CNSI did not induce higher apoptosis levels
      either. The slight oxidative stress was observed in RES organs at high dosages at
      day 7 post-exposure. The implication to the clinical applications and
      toxicological evaluations of carbon nanomaterials is discussed.

PMID- 29186021
TI  - An Efficient Audio Coding Scheme for Quantitative and Qualitative Large Scale
      Acoustic Monitoring Using the Sensor Grid Approach.
AB  - The spreading of urban areas and the growth of human population worldwide raise
      societal and environmental concerns. To better address these concerns, the
      monitoring of the acoustic environment in urban as well as rural or wilderness
      areas is an important matter. Building on the recent development of low cost
      hardware acoustic sensors, we propose in this paper to consider a sensor grid
      approach to tackle this issue. In this kind of approach, the crucial question is
      the nature of the data that are transmitted from the sensors to the processing
      and archival servers. To this end, we propose an efficient audio coding scheme
      based on third octave band spectral representation that allows: (1) the
      estimation of standard acoustic indicators; and (2) the recognition of acoustic
      events at state-of-the-art performance rate. The former is useful to provide
      quantitative information about the acoustic environment, while the latter is
      useful to gather qualitative information and build perceptually motivated
      indicators using for example the emergence of a given sound source. The coding
      scheme is also demonstrated to transmit spectrally encoded data that, reverted to
      the time domain using state-of-the-art techniques, are not intelligible, thus
      protecting the privacy of citizens.

PMID- 29186022
TI  - Investigation of Binding Modes and Functional Surface of Scorpion Toxins ANEP to
      Sodium Channels 1.7.
AB  - The depressant beta toxin anti-neuroexcitation peptide (ANEP) from the Chinese
      scorpion Buthus martensii Karsch has analgesic activity by interacting with
      receptor site 4 of the voltage-gated sodium channels (VGSCs). Here, with
      molecular dynamics simulations, we examined the binding modes between ANEP and
      the site 4 of mice sodium channel 1.7 (mNav1.7), a subtype of VGSCs related to
      peripheral pain. Homology modeling, molecular mechanics, and molecular dynamics
      in the biomembrane environment were adopted. The results suggested that ANEP
      bound to the resting site 4 mainly by amino acid residues in the beta2-beta3 loop
      and the 'NC' domains, and the activate site 4 mainly by amino acid residues in
      the hydrophobic domain of N-groove and residues in the 'pharmacophore'. Effects
      analysis of 14 mutants in the predicted functional domains of ANEP on mouse
      twisting models showed that the analgesic activity of mutants L15 and E24 of the
      'pharmacophore', W36, T37, W38, and T39 forming the loop between the beta2- and
      beta3-strands and N8, V12, C60, and K64 in the NC domain increased distinctly
      after these residues were substituted for Ala, respectively. The binding modes
      and the active sites predicted were consistent with available mutagenesis data,
      and which is meaningful to understand the related mechanisms of ANEP for Nav1.7.

PMID- 29186023
TI  - Highly Sensitive FPW-Based Microsystem for Rapid Detection of
      Tetrahydrocannabinol in Human Urine.
AB  - This paper presents a highly sensitive flexural plate-wave (FPW)-based
      microsystem for rapid detection of tetrahydrocannabinol (THC) in human urine.
      First, a circular-type interdigital transducer (IDT) was integrated with a
      circular-type silicon-grooved reflective grating structure (RGS) to reduce
      insertion loss. Then, with lower insertion loss (-38.758 dB), the FPW device was
      used to develop a novel THC biosensor, and the results reveal that this FPW-THC
      biosensor has low detection limit (1.5625 ng/mL) and high mass-sensitivity
      (126.67 cm2/g). Finally, this biosensor was integrated with field-programmable
      gate array (FPGA) board and discrete components for prototyping a FPW readout
      system, whose maximum error was 12.378 kHz to ensure that the linearity of
      detection up to R-square is equal to 0.9992.

PMID- 29186020
TI  - Applications of Alternative Nucleases in the Age of CRISPR/Cas9.
AB  - Breakthroughs in the development of programmable site-specific nucleases,
      including zinc-finger nucleases (ZFNs), transcription activator-like effector
      nucleases (TALENs), meganucleases (MNs), and most recently, the clustered
      regularly interspaced short palindromic repeats (CRISPR) associated proteins
      (including Cas9) have greatly enabled and accelerated genome editing. By
      targeting double-strand breaks to user-defined locations, the rates of DNA repair
      events are greatly enhanced relative to un-catalyzed events at the same sites.
      However, the underlying biology of each genome-editing nuclease influences the
      targeting potential, the spectrum of off-target cleavages, the ease-of-use, and
      the types of recombination events at targeted double-strand breaks. No single
      genome-editing nuclease is optimized for all possible applications. Here, we
      focus on the diversity of nuclease domains available for genome editing,
      highlighting biochemical properties and the potential applications that are best
      suited to each domain.

PMID- 29186024
TI  - Gold Nanoparticles Used as Protein Scavengers Enhance Surface Plasmon Resonance
      Signal.
AB  - Although several researchers had reported on methodologies for surface plasmon
      resonance (SPR) signal amplification based on the use of nanoparticles (NPs), the
      majority addressed the sandwich technique and low protein concentration. In this
      work, a different approach for SPR signal enhancement based on the use of gold
      NPs was evaluated. The method was used in the detection of two lectins, peanut
      agglutinin (PNA) and concanavalin A (ConA). Gold NPs were functionalized with
      antibodies anti-PNA and anti-ConA, and these NPs were used as protein scavengers
      in a solution. After being incubated with solutions of PNA or ConA, the gold NPs
      coupled with the collected lectins were injected on the sensor containing the
      immobilized antibodies. The signal amplification provided by this method was
      compared to the signal amplification provided by the direct coupling of PNA and
      ConA to gold NPs. Furthermore, both methods, direct coupling and gold NPs as
      protein scavengers, were compared to the direct detection of PNA and ConA in
      solution. Compared to the analysis of free protein, the direct coupling of PNA
      and ConA to gold NPs resulted in a signal amplification of 10-40-fold and a 13
      fold decrease of the limit of detection (LOD), whereas the use of gold NPs as
      protein scavengers resulted in an SPR signal 40-50-times higher and an LOD 64
      times lower.

PMID- 29186025
TI  - Effect of CaO on NOx Reduction by Selective Non-Catalytic Reduction under
      Variable Gas Compositions in a Simulated Cement Precalciner Atmosphere.
AB  - High-concentration CaO particles and gas compositions have a significant
      influence on NOx reduction by selective non-catalytic reduction (SNCR) in cement
      precalciners. The effect of gas composition on NOx reduction by SNCR with NH3 was
      studied in a cement precalciner atmosphere with and without CaO at 700-1100 
      degrees C. It was found that CaO significantly lowers NOx reduction efficiency
      between 750  degrees C and 1000  degrees C, which is attributed to the catalytic
      oxidation of NH3 to NO. Although increasing NH3 concentration was advantageous to
      NOx reduction, the existence of CaO led to the opposite result at 750-900 
      degrees C. Adding H2O can suppress the negative effect of CaO on NOx reduction.
      Decreasing O2 content from 10% to 1% shifts the temperature range in which CaO
      has a significant effect from 750-1000  degrees C to 800-1050  degrees C. CO has
      a variety of influences on the CaO effect under different experimental
      conditions. The influences of NH3, H2O, O2, and CO on the effect of CaO can be
      attributed to the impacts of the gas compositions on gas-phase NH3 conversion,
      gas-solid catalytic NH3 oxidation, or both processes. A proposed pathway for the
      effect of gas compositions on NOx reduction in CaO-containing SNCR process was
      developed that well predicted the CaO-containing SNCR process.

PMID- 29186026
TI  - Antimicrobial Activity of Bee Venom and Melittin against Borrelia burgdorferi.
AB  - Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium
      Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse
      often occurs after the discontinuation of antimicrobial agents. The reason for
      relapse remains unknown, however previous studies suggest the possible presence
      of antibiotic resistant Borrelia round bodies, persisters and attached biofilm
      forms. Thus, there is an urgent need to find antimicrobial agents suitable to
      eliminate all known forms of B. burgdorferi. In this study, natural antimicrobial
      agents such as Apis mellifera venom and a known component, melittin, were tested
      using SYBR Green I/PI, direct cell counting, biofilm assays combined with
      LIVE/DEAD and atomic force microscopy methods. The obtained results were compared
      to standalone and combinations of antibiotics such as Doxycycline, Cefoperazone,
      Daptomycin, which were recently found to be effective against Borrelia
      persisters. Our findings showed that both bee venom and melittin had significant
      effects on all the tested forms of B. burgdorferi. In contrast, the control
      antibiotics when used individually or even in combinations had limited effects on
      the attached biofilm form. These findings strongly suggest that whole bee venom
      or melittin could be effective antimicrobial agents for B. burgdorferi; however,
      further research is necessary to evaluate their effectiveness in vivo, as well as
      their safe and effective delivery method for their therapeutic use.

PMID- 29186027
TI  - A New Low-Temperature Electrochemical Hydrocarbon and NOx Sensor.
AB  - In this article, a new investigation on a low-temperature electrochemical
      hydrocarbon and NOx sensor is presented. Based on the mixed-potential-based
      sensing scheme, the sensor is constructed using platinum and metal oxide
      electrodes, along with an Yttria-Stabilized Zirconia (YSZ)/Strontium Titanate
      (SrTiO3) thin-film electrolyte. Unlike traditional mixed-potential sensors which
      operate at higher temperatures (>400  degrees C), this potentiometric sensor
      operates at 200  degrees C with dominant hydrocarbon (HC) and NOx response in the
      open-circuit and biased modes, respectively. The possible low-temperature
      operation of the sensor is speculated to be primarily due to the enhanced oxygen
      ion conductivity of the electrolyte, which may be attributed to the space charge
      effect, epitaxial strain, and atomic reconstruction at the interface of the
      YSZ/STO thin film. The response and recovery time for the NOx sensor are found to
      be 7 s and 8 s, respectively. The sensor exhibited stable response even after 120
      days of testing, with an 11.4% decrease in HC response and a 3.3% decrease in NOx
      response.

PMID- 29186028
TI  - Responsive Proteins in Wheat Cultivars with Contrasting Nitrogen Efficiencies
      under the Combined Stress of High Temperature and Low Nitrogen.
AB  - Productivity of wheat (Triticumaestivum) is markedly affected by high temperature
      and nitrogen deficiency. Identifying the functional proteins produced in response
      to these multiple stresses acting in a coordinated manner can help in developing
      tolerance in the crop. In this study, two wheat cultivars with contrasting
      nitrogen efficiencies (N-efficient VL616 and N-inefficient UP2382) were grown in
      control conditions, and under a combined stress of high temperature (32  degrees
      C) and low nitrogen (4 mM), and their leaf proteins were analysed in order to
      identify the responsive proteins. Two-dimensional electrophoresis unravelled
      sixty-one proteins, which varied in their expression in wheat, and were
      homologous to known functional proteins involved in biosynthesis, carbohydrate
      metabolism, energy metabolism, photosynthesis, protein folding, transcription,
      signalling, oxidative stress, water stress, lipid metabolism, heat stress
      tolerance, nitrogen metabolism, and protein synthesis. When exposed to high
      temperature in combination with low nitrogen, wheat plants altered their protein
      expression as an adaptive means to maintain growth. This response varied with
      cultivars. Nitrogen-efficient cultivars showed a higher potential of redox
      homeostasis, protein stability, osmoprotection, and regulation of nitrogen
      levels. The identified stress-responsive proteins can pave the way for enhancing
      the multiple-stress tolerance in wheat and developing a better understanding of
      its mechanism.

PMID- 29186030
TI  - Buprofezin Is Metabolized by CYP353D1v2, a Cytochrome P450 Associated with
      Imidacloprid Resistance in Laodelphax striatellus.
AB  - CYP353D1v2 is a cytochrome P450 related to imidacloprid resistance in Laodelphax
      striatellus. This work was conducted to examine the ability of CYP353D1v2 to
      metabolize other insecticides. Carbon monoxide difference spectra analysis
      indicates that CYP353D1v2 was successfully expressed in insect cell Sf9. The
      catalytic activity of CYP353D1v2 relating to degrading buprofezin, chlorpyrifos,
      and deltamethrin was tested by measuring substrate depletion and analyzing the
      formation of metabolites. The results showed the nicotinamide-adenine
      dinucleotide phosphate (NADPH)-dependent depletion of buprofezin (eluting at 8.7
      min) and parallel formation of an unknown metabolite (eluting 9.5 min). However,
      CYP353D1v2 is unable to metabolize deltamethrin and chlorpyrifos. The recombinant
      CYP353D1v2 protein efficiently catalyzed the model substrate p-nitroanisole with
      a maximum velocity of 9.24 nmol/min/mg of protein and a Michaelis constant of Km
      = 6.21 uM. In addition, imidacloprid was metabolized in vitro by the recombinant
      CYP353D1v2 microsomes (catalytic constant Kcat) 0.064 pmol/min/pmol P450, Km =
      6.41 uM. The mass spectrum of UPLC-MS analysis shows that the metabolite was a
      product of buprofezin, which was buprofezin sulfone. This result provided direct
      evidence that L. striatellus cytochrome P450 CYP353D1v2 is capable of
      metabolizing imidacloprid and buprofezin.

PMID- 29186029
TI  - MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function.
AB  - MUC1 is a membrane-bound mucin expressed on the apical surfaces of most mucosal
      epithelial cells. In normal lung epithelia, MUC1 is a binding site for
      Pseudomonas aeruginosa, an opportunistic human pathogen of great clinical
      importance. It has now been established that MUC1 also serves an anti
      inflammatory role in the airways that is initiated late in the course of a
      bacterial infection and is mediated through inhibition of Toll-like receptor
      (TLR) signaling. MUC1 expression was initially shown to interfere with TLR5
      signaling in response to P. aeruginosa flagellin, but has since been extended to
      other TLRs. These new findings point to an immunomodulatory role for MUC1 during
      P. aeruginosa lung infection, particularly during the resolution phase of
      inflammation. This review briefly summarizes the recent characterization of
      MUC1's anti-inflammatory properties in both the respiratory tract and
      extrapulmonary tissues.

PMID- 29186031
TI  - Lipopolysaccharide Modifies Glycerol Permeability and Metabolism in 3T3-L1
      Adipocytes.
AB  - Aquaglyceroporins-aquaporin membrane channels (AQP) that conduct glycerol and
      other small neutral solutes in addition to water-play major roles in obesity. In
      adipocytes, aquaglyceroporins mediate glycerol uptake and release across the
      plasma membrane, which are two key steps for triacylglycerols (TAGs) synthesis
      (lipogenesis) and hydrolysis (lipolysis). The aim of this study was to assess
      both glycerol permeability and metabolism in undifferentiated 3T3-L1 cells (UDCs)
      as well as in untreated (CTL-DCs) versus lipopolysaccharide (LPS-DCs)-treated
      differentiated 3T3-L1 adipocytes. Glycerol release, TAGs content and whole
      membrane glycerol permeability were significantly increased in DCs as compared to
      UDCs. Moreover, in DCs, LPS treatment significantly increased TAGs content and
      decreased glycerol permeability. In addition, a significant reduction in whole
      membrane glycerol permeability was observed in LPS-DCs as compared to CTL-DCs.
      The relative contributions of AQP3, AQP7 and AQP9 (facilitated diffusion), as
      well as that of the phospholipid bilayer (simple diffusion), to the whole
      membrane glycerol permeability, were estimated biophysically in UDCs, CTL-DCs and
      LPS-DCs, using selective AQP inhibitors. Further studies will be required to
      determine if modifications in either subcellular localization and/or activity of
      aquaglyceroporins could account for the data herein. Nevertheless, our findings
      provide novel insights in understanding the LPS-induced adipocyte hypertrophy
      that accompanies obesity.

PMID- 29186032
TI  - In Vivo Activity of LCB 01-0699, a Prodrug of LCB 01-0648, against Staphylococcus
      aureus.
AB  - LCB01-0648 is a novel oxazolidinone compound that shows potent antibacterial
      activities against most Gram-positive cocci, including the multi-drug resistant
      Staphylococcusaureus. In this study, in vivo activity of LCB01-0699, a LCB01-0648
      prodrug, against S.aureus was evaluated in comparison with that of Linezolid. The
      results of the systemic infection study demonstrated that LCB01-0699 was more
      potent than Linezolid against methicillin-susceptible and -resistant S. aureus
      strains. The in vivo efficacy of LCB01-0699 against methicillin-susceptible and 
      resistant S. aureus strains in a skin infection model showed more potent activity
      than Linezolid. LCB01-0699 shows potent in vivo activity against methicillin
      susceptible and -resistant S. aureus strains, suggesting that LCB01-0699 would be
      a novel candidate for the treatment of these infectious diseases caused by S.
      aureus.

PMID- 29186033
TI  - Comparative Flight Activities and Pathogen Load of Two Stocks of Honey Bees
      Reared in Gamma-Irradiated Combs.
AB  - Gamma irradiation is known to inactivate various pathogens that negatively affect
      honey bee health. Bee pathogens, such as Deformed wing virus (DWV) and Nosema
      spp., have a deleterious impact on foraging activities and bee survival, and have
      been detected in combs. In this study, we assessed the effects of gamma
      irradiation on the flight activities, pathogen load, and survival of two honey
      bee stocks that were reared in irradiated and non-irradiated combs. Overall, bee
      genotype influenced the average number of daily flights, the total number of
      foraging flights, and total flight duration, in which the Russian honey bees
      outperformed the Italian honey bees. Exposing combs to gamma irradiation only
      affected the age at first flight, with worker bees that were reared in non
      irradiated combs foraging prematurely compared to those reared in irradiated
      combs. Precocious foraging may be associated with the higher levels of DWV in
      bees reared in non-irradiated combs and also with the lower amount of pollen
      stores in colonies that used non-irradiated combs. These data suggest that gamma
      irradiation of combs can help minimize the negative impact of DWV in honey bees.
      Since colonies with irradiated combs stored more pollen than those with non
      irradiated combs, crop pollination efficiency may be further improved when mite
      resistant stocks are used, since they performed more flights and had longer
      flight durations.

PMID- 29186035
TI  - Are Changes in Neighbourhood Perceptions Associated with Changes in Self-Rated
      Mental Health in Adults? A 13-Year Repeat Cross-Sectional Study, UK.
AB  - The aim of this study was to examine changes in neighbourhood perceptions on self
      rated mental health problems over time, and to explore demographic, geographic
      and socio-economic factors as determinants of increased or decreased anxiety and
      depression symptoms. We conducted a repeat cross-sectional study of individuals
      (N: 4480) living in the same areas of west central Scotland in 1997 and 2010.
      Individuals were asked to complete a questionnaire at both time-points,
      containing 14 questions relating to neighbourhood perceptions and the Hospital
      Anxiety and Depression Scale (HADS). A three-level linear regression model was
      fitted to HADS scores and changes in neighbourhood perceptions over time;
      controlling for a number of individual and area-level variables. Overall, area
      level mean HADS scores decreased from 1997 to 2010. When adjusted for individual
      and area-level variables, this decrease did not remain for HADS anxiety. Applying
      an overall 14-scale neighbourhood perception measure, worsening neighbourhood
      perceptions were associated with small increases in depression (0.04, 95%
      confidence interval (CI) 0.01 to 0.07) and anxiety (0.04, 95% CI 0.00 to 0.08)
      scores over time. This highlights a need for local and national policy to target
      areas where neighbourhood characteristics are substantially deteriorating in
      order to ensure the mental health of individuals does not worsen.

PMID- 29186036
TI  - A New Bone Substitute Developed from 3D-Prints of Polylactide (PLA) Loaded with
      Collagen I: An In Vitro Study.
AB  - Although a lot of research has been performed, large segmental bone defects
      caused by trauma, infection, bone tumors or revision surgeries still represent
      big challenges for trauma surgeons. New and innovative bone substitutes are
      needed. Three-dimensional (3D) printing is a novel procedure to create 3D porous
      scaffolds that can be used for bone tissue engineering. In the present study,
      solid discs as well as porous cage-like 3D prints made of polylactide (PLA) are
      coated or filled with collagen, respectively, and tested for biocompatibility and
      endotoxin contamination. Microscopic analyses as well as proliferation assays
      were performed using various cell types on PLA discs. Stromal-derived factor (SDF
      1) release from cages filled with collagen was analyzed and the effect on
      endothelial cells tested. This study confirms the biocompatibility of PLA and
      demonstrates an endotoxin contamination clearly below the FDA (Food and Drug
      Administration) limit. Cells of various cell types (osteoblasts, osteoblast-like
      cells, fibroblasts and endothelial cells) grow, spread and proliferate on PLA
      printed discs. PLA cages loaded with SDF-1 collagen display a steady SDF-1
      release, support cell growth of endothelial cells and induce neo-vessel
      formation. These results demonstrate the potential for PLA scaffolds printed with
      an inexpensive desktop printer in medical applications, for example, in bone
      tissue engineering.

PMID- 29186037
TI  - Symbiotic Sensing for Energy-Intensive Tasks in Large-Scale Mobile Sensing
      Applications.
AB  - Energy consumption is a critical performance and user experience metric when
      developing mobile sensing applications, especially with the significantly growing
      number of sensing applications in recent years. As proposed a decade ago when
      mobile applications were still not popular and most mobile operating systems were
      single-tasking, conventional sensing paradigms such as opportunistic sensing and
      participatory sensing do not explore the relationship among concurrent
      applications for energy-intensive tasks. In this paper, inspired by social
      relationships among living creatures in nature, we propose a symbiotic sensing
      paradigm that can conserve energy, while maintaining equivalent performance to
      existing paradigms. The key idea is that sensing applications should
      cooperatively perform common tasks to avoid acquiring the same resources multiple
      times. By doing so, this sensing paradigm executes sensing tasks with very little
      extra resource consumption and, consequently, extends battery life. To evaluate
      and compare the symbiotic sensing paradigm with the existing ones, we develop
      mathematical models in terms of the completion probability and estimated energy
      consumption. The quantitative evaluation results using various parameters
      obtained from real datasets indicate that symbiotic sensing performs better than
      opportunistic sensing and participatory sensing in large-scale sensing
      applications, such as road condition monitoring, air pollution monitoring, and
      city noise monitoring.

PMID- 29186034
TI  - Cellular and Oxidative Mechanisms Associated with Interleukin-6 Signaling in the
      Vasculature.
AB  - Reactive oxygen species, particularly superoxide, promote endothelial dysfunction
      and alterations in vascular structure. It is increasingly recognized that
      inflammatory cytokines, such as interleukin-6 (IL-6), contribute to endothelial
      dysfunction and vascular hypertrophy and fibrosis. IL-6 is increased in a number
      of cardiovascular diseases, including hypertension. IL-6 is also associated with
      a higher incidence of future cardiovascular events and all-cause mortality. Both
      immune and vascular cells produce IL-6 in response to a number of stimuli, such
      as angiotensin II. The vasculature is responsive to IL-6 produced from vascular
      and non-vascular sources via classical IL-6 signaling involving a membrane-bound
      IL-6 receptor (IL-6R) and membrane-bound gp130 via Jak/STAT as well as SHP2
      dependent signaling pathways. IL-6 signaling is unique because it can also occur
      via a soluble IL-6 receptor (sIL-6R) which allows for IL-6 signaling in tissues
      that do not normally express IL-6R through a process referred to as IL-6 trans
      signaling. IL-6 signaling mediates a vast array of effects in the vascular wall,
      including endothelial activation, vascular permeability, immune cell recruitment,
      endothelial dysfunction, as well as vascular hypertrophy and fibrosis. Many of
      the effects of IL-6 on vascular function and structure are representative of loss
      or reductions in nitric oxide (NO) bioavailability. IL-6 has direct effects on
      endothelial nitric oxide synthase activity and expression as well as increasing
      vascular superoxide, which rapidly inactivates NO thereby limiting NO
      bioavailability. The goal of this review is to highlight both the cellular and
      oxidative mechanisms associated with IL-6-signaling in the vascular wall in
      general, in hypertension, and in response to angiotensin II.

PMID- 29186038
TI  - Molecular Screening of 43 Brazilian Families Diagnosed with Leber Congenital
      Amaurosis or Early-Onset Severe Retinal Dystrophy.
AB  - Leber congenital amaurosis (LCA) is a severe disease that leads to complete
      blindness in children, typically before the first year of life. Due to the
      clinical and genetic heterogeneity among LCA and other retinal diseases,
      providing patients with a molecular diagnosis is essential to assigning an
      accurate clinical diagnosis. Using our gene panel that targets 300 genes that are
      known to cause retinal disease, including 24 genes reported to cause LCA, we
      sequenced 43 unrelated probands with Brazilian ancestry. We identified 42 unique
      variants and were able to assign a molecular diagnosis to 30/43 (70%) Brazilian
      patients. Among these, 30 patients were initially diagnosed with LCA or a form of
      early-onset retinal dystrophy, 17 patients harbored mutations in LCA-associated
      genes, while 13 patients had mutations in genes that were reported to cause other
      diseases involving the retina.

PMID- 29186039
TI  - Health Diagnosis of Major Transportation Infrastructures in Shanghai Metropolis
      Using High-Resolution Persistent Scatterer Interferometry.
AB  - Since the Persistent Scatterer Synthetic Aperture Radar (SAR) Interferometry
      (PSI) technology allows the detection of ground subsidence with millimeter
      accuracy, it is becoming one of the most powerful and economical means for health
      diagnosis of major transportation infrastructures. However, structures of
      different types may suffer from various levels of localized subsidence due to the
      different structural characteristics and subsidence mechanisms. Moreover, in the
      complex urban scenery, some segments of these infrastructures may be sheltered by
      surrounding buildings in SAR images, obscuring the desirable signals. Therefore,
      the subsidence characteristics on different types of structures should be
      discussed separately and the accuracy of persistent scatterers (PSs) should be
      optimized. In this study, the PSI-based subsidence mapping over the entire
      transportation network of Shanghai (more than 10,000 km) is illustrated,
      achieving the city-wide monitoring specifically along the elevated roads, ground
      highways and underground subways. The precise geolocation and structural
      characteristics of infrastructures were combined to effectively guide more
      accurate identification and separation of PSs along the structures. The
      experimental results from two neighboring TerraSAR-X stacks from 2013 to 2016
      were integrated by joint estimating the measurements in the overlapping area,
      performing large-scale subsidence mapping and were validated by leveling data,
      showing highly consistent in terms of subsidence velocities and time-series
      displacements. Spatial-temporal subsidence patterns on each type of
      infrastructures are strongly dependent on the operational durations and
      structural characteristics, as well as the variation of the foundation soil
      layers.

PMID- 29186040
TI  - Silver Nanoparticle Modified Electrode Covered by Graphene Oxide for the Enhanced
      Electrochemical Detection of Dopamine.
AB  - Several neurological disorders such as Alzheimer's disease and Parkinson's
      disease have become a serious impediment to aging people nowadays. One of the
      efficient methods used to monitor these neurological disorders is the detection
      of neurotransmitters such as dopamine. Metal materials, such as gold and
      platinum, are widely used in this electrochemical detection method; however, low
      sensitivity and linearity at low dopamine concentrations limit the use of these
      materials. To overcome these limitations, a silver nanoparticle (SNP) modified
      electrode covered by graphene oxide for the detection of dopamine was newly
      developed in this study. For the first time, the surface of an indium tin oxide
      (ITO) electrode was modified using SNPs and graphene oxide sequentially through
      the electrochemical deposition method. The developed biosensor provided
      electrochemical signal enhancement at low dopamine concentrations in comparison
      with previous biosensors. Therefore, our newly developed SNP modified electrode
      covered by graphene oxide can be used to monitor neurological diseases through
      electrochemical signal enhancement at low dopamine concentrations.

PMID- 29186041
TI  - Enhanced Intestinal Permeability of Bufalin by a Novel Bufalin-Peptide-Dendrimer
      Inclusion through Caco-2 Cell Monolayer.
AB  - Bufalin (BFL) has excellent physiological activities such as defending tumors,
      improving cardiac function, and so on. However, due to its poor water-solubility
      and bioavailability, the clinical application of BFL remains limited. In order to
      improve bioavailability of BFL, in our previous research, a novel peptide
      dendrimer (PD) was synthesized and applied to encapsulate BFL. In the present
      study, we investigate the absorption property and mechanism of BFL in free form
      and BFL-peptide-dendrimer inclusion (BPDI) delivery system by using the Caco-2
      cell monolayer model in vitro. The apparent permeability coefficient (Papp)
      values of BFL in free or BPDI form were over 1.0 * 10-6 cm/s. Meanwhile, their
      almost equal bi-directional transport and linear transport percentage with time
      and concentration course indicated that BFL in both forms was absorbed mainly
      through passive diffusion. The most important result is that the Papp values of
      BFL increased about three-fold more BPDI than those of its free form, which
      indicated the intestinal permeability of BFL could be improved while BFL was
      encapsulated in BPDI form. Therefore, PD encapsulation may be a potential
      delivery system to increase the bioavailability of BFL.

PMID- 29186043
TI  - Trend in H2S Biology and Medicine Research-A Bibliometric Analysis.
AB  - The biological and medical importance of hydrogen sulfide (H2S) has been
      recognized for decades. The aim of this bibliometric study is to analyze the
      quantity and quality of publications in H2S biology and medicine (H2SBM) based on
      the databases of Web of Science and Google Scholar. A total of 5881 publications
      published between 1990 and 2016 were analyzed. The number of H2SBM papers
      published before 2004 was below 100 annually, but thereafter this number rapidly
      increased and peaked in 2015 with more than 7-fold increase. All publications
      related to H2SBM research achieved a total h-index of 136 and were cited 123,074
      times. The most published disciplines in H2S biomedicine research were the
      cardiovascular system (8.5%), neuroscience (6.5%), and gastroenterology
      hepatology (4.7%). The country with the greatest number of publications in the
      H2SBM research field was the USA with 1765 (30.0%) publications, followed by
      China with 995 (16.9%) publications and Japan with 555 (9.4%) publications. The
      top 3 most published institutes were National University of Singapore, Peking
      University in China, and University of Groningen in Netherlands. Nitric Oxide
      Biology and Chemistry was the most exploited journal for H2SBM publications with
      461 articles, followed by FASEB Journal with 200 publications and Antioxidants
      Redox Signaling with 116 publications. The most highly cited publications and
      researchers in H2SBM research were also unmasked from this bibliometric analysis.
      Collectively, H2SBM publications exhibit a continuous trend of increase,
      reflecting the increased H2SBM research intensity and diversity globally.

PMID- 29186042
TI  - 2-Substituted Aniline as a Simple Scaffold for LuxR-Regulated QS Modulation.
AB  - The ability of the 2-substituted aniline motif to serve as a scaffold for
      designing potential LuxR-regulated quorum sensing (QS) modulators has been
      investigated, using docking experiments and biological evaluation of a series of
      15 specially synthesized compounds. Aniline, 2-acetyl-aniline and 2-nitroaniline
      were considered, as well as their N-acylated derivatives. Docking experiments
      showed that the 2-substituted aniline motif fits within the LuxR binding site at
      the place of the lactone moiety of AHL, and the biological evaluation revealed QS
      antagonisitic activity for several compounds, validating the hypothesis that this
      scaffold acts on QS. Structure activity relationships are discussed regarding
      interactions with the key residues of the LuxR binding site, showing significant
      variations in the H-bonding pattern.

PMID- 29186044
TI  - Platinum-Catalyzed Allylation of 2,3-Disubstituted Indoles with Allylic Acetates.
AB  - Given the importance of heterocycle indole derivatives, much effort has been
      directed toward the development of methods for functionalization of the indole
      nucleus at N1 and C3 sites. Moreover, the platinum-catalyzed allyation of
      nucleophiles was an established and efficient way, which has been applied to
      medicinal and organic chemistry. In our research, the platinum-catalyzed 2,3
      disubstitued indoles with allylic acetates was investigated under different
      conditions. Herein, we established a simple, convenient, and efficient method,
      which afforded high yield of allylated indoles.

PMID- 29186045
TI  - Resveratrol-Induced Effects on Body Fat Differ Depending on Feeding Conditions.
AB  - Science constantly seeks to identify new molecules that could be used as dietary
      functional ingredients in the fight against obesity and its co-morbidities. Among
      them, polyphenols represent a group of molecules of increasing interest. One of
      the most widely studied polyphenols is resveratrol (trans-3,4',5
      trihydroxystilbene), which has been proposed as an "energy restriction mimetic"
      because it can exert energy restriction-like effects. The aim of this review is
      to analyze the effects of resveratrol on obesity under different feeding
      conditions, such as overfeeding, normal feeding, and energy restriction, in
      animals and humans. The vast majority of the studies reported have addressed the
      administration of resveratrol to animals alongside an obesogenic diet. Under
      these experimental conditions usually a decreased body weight amount was found.
      To date, studies that focus on the effects of resveratrol under normal feeding or
      energy restriction conditions in animals and humans are scarcer. In these studies
      no changes in body fat were reported. After analyzing the results obtained under
      overfeeding, normal feeding, and energy restriction conditions, it can be stated
      that resveratrol is useful in reducing body fat accumulation, and thus preventing
      obesity. Nevertheless, for ethical reasons, these results have been obtained in
      animals. By contrast, there are no evidences showing the usefulness of this
      phenolic compound in reducing previously accumulated body fat. Consequently, as
      of yet, there is not scientific support for proposing resveratrol as a new anti
      obesity treatment tool.

PMID- 29186046
TI  - Synthesis and Evaluation of Thiochroman-4-One Derivatives as Potential
      Leishmanicidal Agents.
AB  - The S-containing heterocyclic compounds benzothiopyrans or thiochromones stand
      out as having promising biological activities due to their structural
      relationship with chromones (benzopyrans), which are widely known as privileged
      scaffolds in medicinal chemistry. In this work, we report the synthesis of 35
      thiochromone derivatives and the in vitro antileishmanial and cytotoxic
      activities. Compounds were tested against intracellular amastigotes of Leishmania
      panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL
      1593.2). Compounds bearing a vinyl sulfone moiety, 4h, 4i, 4j, 4k, 4l and 4m,
      displayed the highest antileishmanial activity, with EC50 values lower than 10
      MUM and an index of selectivity over 100 for compounds 4j and 4l. When the double
      bond or the sulfone moiety was removed, the activity decreased. Our results show
      that thiochromones bearing a vinyl sulfone moiety are endowed with high
      antileishmanial activity and low cytotoxicity.

PMID- 29186047
TI  - Properties and Applications of High Emissivity Composite Films Based on Far
      Infrared Ceramic Powder.
AB  - Polymer matrix composite materials that can emit radiation in the far-infrared
      region of the spectrum are receiving increasing attention due to their ability to
      significantly influence biological processes. This study reports on the far
      infrared emissivity property of composite films based on far-infrared ceramic
      powder. X-ray fluorescence spectrometry, Fourier transform infrared spectroscopy,
      thermogravimetric analysis, and X-ray powder diffractometry were used to evaluate
      the physical properties of the ceramic powder. The ceramic powder was found to be
      rich in aluminum oxide, titanium oxide, and silicon oxide, which demonstrate high
      far-infrared emissivity. In addition, the micromorphology, mechanical
      performance, dynamic mechanical properties, and far-infrared emissivity of the
      composite were analyzed to evaluate their suitability for strawberry storage. The
      mechanical properties of the far-infrared radiation ceramic (cFIR) composite
      films were not significantly influenced (p >= 0.05) by the addition of the
      ceramic powder. However, the dynamic mechanical analysis (DMA) properties of the
      cFIR composite films, including a reduction in damping and shock absorption
      performance, were significant influenced by the addition of the ceramic powder.
      Moreover, the cFIR composite films showed high far-infrared emissivity, which has
      the capability of prolonging the storage life of strawberries. This research
      demonstrates that cFIR composite films are promising for future applications.

PMID- 29186048
TI  - Three New Malyngamides from the Marine Cyanobacterium Moorea producens.
AB  - Three new compounds of the malyngamide series, 6,8-di-O-acetylmalyngamide 2 (1),
      6-O-acetylmalyngamide 2 (2), and N-demethyl-isomalyngamide I (3), were isolated
      from the marine cyanobacterium Moorea producens. Their structures were determined
      by spectroscopic analysis and chemical derivatization and degradation. These
      compounds stimulated glucose uptake in cultured L6 myotubes. In particular, 6,8
      di-O-acetylmalyngamide 2 (1) showed potent activity and activated adenosine
      monophosphate-activated protein kinase (AMPK).

PMID- 29186051
TI  - First Results of Using a UVTron Flame Sensor to Detect Alpha-Induced Air
      Fluorescence in the UVC Wavelength Range.
AB  - In this work, a robust stand-off alpha detection method using the secondary
      effects of alpha radiation has been sought. Alpha particles ionise the
      surrounding atmosphere as they travel. Fluorescence photons produced as a
      consequence of this can be used to detect the source of the alpha emissions. This
      paper details experiments carried out to detect this fluorescence, with the focus
      on photons in the ultraviolet C (UVC) wavelength range (180-280 nm). A detector,
      UVTron R9533 (Hamamatsu, 325-6, Sunayama-cho, Naka-ku, Hamamatsu City, Shizuoka
      Pref., 430-8587, Japan), designed to detect the UVC emissions from flames for
      fire alarm purposes, was tested in various gas atmospheres with a 210Po alpha
      source to determine if this could provide an avenue for stand-off alpha
      detection. The results of the experiments show that this detector is capable of
      detecting alpha-induced air fluorescence in normal indoor lighting conditions, as
      the interference from daylight and artificial lighting is less influential on
      this detection system which operates below the UVA and UVB wavelength ranges (280
      315 nm and 315-380 nm respectively). Assuming a standard 1 r 2 drop off in
      signal, the limit of detection in this configuration can be calculated to be
      approximately 240 mm, well beyond the range of alpha-particles in air, which
      indicates that this approach could have potential for stand-off alpha detection.
      The gas atmospheres tested produced an increase in the detector count, with xenon
      having the greatest effect with a measured 52% increase in the detector response
      in comparison to the detector response in an air atmosphere. This type of alpha
      detection system could be operated at a distance, where it would potentially
      provide a more cost effective, safer, and faster solution in comparison with
      traditional alpha detection methods to detect and characterise alpha
      contamination in nuclear decommissioning and security applications.

PMID- 29186049
TI  - What Does "the RNA World" Mean to "the Origin of Life"?
AB  - Corresponding to life's two distinct aspects: Darwinian evolution and self
      sustainment, the origin of life should also split into two issues: the origin of
      Darwinian evolution and the arising of self-sustainment. Because the "self
      sustainment" we concern about life should be the self-sustainment of a relevant
      system that is "defined" by its genetic information, the self-sustainment could
      not have arisen before the origin of Darwinian evolution, which was just marked
      by the emergence of genetic information. The logic behind the idea of the RNA
      world is not as tenable as it has been believed. That is, genetic molecules and
      functional molecules, even though not being the same material, could have emerged
      together in the beginning and launched the evolution-provided that the genetic
      molecules can "simply" code the functional molecules. However, due to these or
      those reasons, alternative scenarios are generally much less convincing than the
      RNA world. In particular, when considering the accumulating experimental evidence
      that is supporting a de novo origin of the RNA world, it seems now quite
      reasonable to believe that such a world may have just stood at the very beginning
      of life on the Earth. Therewith, we acquire a concrete scenario for our attempts
      to appreciate those fundamental issues that are involved in the origin of life.
      In the light of those possible scenes included in this scenario, Darwinian
      evolution may have originated at the molecular level, realized upon a functional
      RNA. When two or more functional RNAs emerged, for their efficient cooperation,
      there should have been a selective pressure for the emergence of protocells. But
      it was not until the appearance of the "unitary-protocell", which had all of its
      RNA genes linked into a chromosome, that Darwinian evolution made its full step
      towards the cellular level-no longer severely constrained by the low-grade
      evolution at the molecular level. Self-sustainment did not make sense before
      protocells emerged. The selection pressure that was favoring the exploration of
      more and more fundamental raw materials resulted in an evolutionary tendency of
      life to become more and more self-sustained. New functions for the entities to
      adapt to environments, including those that are involved in the self-sustainment
      per se, would bring new burdens to the self-sustainment-the advantage of these
      functions must overweigh the corresponding disadvantage.

PMID- 29186050
TI  - HPLC-PDA-MS/MS Characterization of Bioactive Secondary Metabolites from Turraea
      fischeri Bark Extract and Its Antioxidant and Hepatoprotective Activities In
      Vivo.
AB  - Turraea fischeri is an East African traditional herb, which is widely used in
      traditional medicine. In this study, we profiled the secondary metabolites in the
      methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds
      were tentatively identified. Several isomers of the flavonolignan cinchonain-I
      and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the
      extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1
      diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing
      antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans.
      Additionally, the extract exhibited promising hepatoprotective activities in D
      galactosamine (D-GaIN) treated rats. A significant reduction in the elevated
      levels of aspartate aminotransferase (AST), total bilirubin, gamma
      glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione
      (GSH) was observed in rats treated with the bark extract in addition to D
      galactosamine when compared with rats treated with D-galactosamine alone. In
      conclusion, T. fischeri is apromising candidate for health-promoting and for
      pharmaceutical applications.

PMID- 29186052
TI  - Cancer Classification Based on Support Vector Machine Optimized by Particle Swarm
      Optimization and Artificial Bee Colony.
AB  - Intelligent optimization algorithms have advantages in dealing with complex
      nonlinear problems accompanied by good flexibility and adaptability. In this
      paper, the FCBF (Fast Correlation-Based Feature selection) method is used to
      filter irrelevant and redundant features in order to improve the quality of
      cancer classification. Then, we perform classification based on SVM (Support
      Vector Machine) optimized by PSO (Particle Swarm Optimization) combined with ABC
      (Artificial Bee Colony) approaches, which is represented as PA-SVM. The proposed
      PA-SVM method is applied to nine cancer datasets, including five datasets of
      outcome prediction and a protein dataset of ovarian cancer. By comparison with
      other classification methods, the results demonstrate the effectiveness and the
      robustness of the proposed PA-SVM method in handling various types of data for
      cancer classification.

PMID- 29186053
TI  - GelSight: High-Resolution Robot Tactile Sensors for Estimating Geometry and
      Force.
AB  - Tactile sensing is an important perception mode for robots, but the existing
      tactile technologies have multiple limitations. What kind of tactile information
      robots need, and how to use the information, remain open questions. We believe a
      soft sensor surface and high-resolution sensing of geometry should be important
      components of a competent tactile sensor. In this paper, we discuss the
      development of a vision-based optical tactile sensor, GelSight. Unlike the
      traditional tactile sensors which measure contact force, GelSight basically
      measures geometry, with very high spatial resolution. The sensor has a contact
      surface of soft elastomer, and it directly measures its deformation, both
      vertical and lateral, which corresponds to the exact object shape and the tension
      on the contact surface. The contact force, and slip can be inferred from the
      sensor's deformation as well. Particularly, we focus on the hardware and software
      that support GelSight's application on robot hands. This paper reviews the
      development of GelSight, with the emphasis in the sensing principle and sensor
      design. We introduce the design of the sensor's optical system, the algorithm for
      shape, force and slip measurement, and the hardware designs and fabrication of
      different sensor versions. We also show the experimental evaluation on the
      GelSight's performance on geometry and force measurement. With the high
      resolution measurement of shape and contact force, the sensor has successfully
      assisted multiple robotic tasks, including material perception or recognition and
      in-hand localization for robot manipulation.

PMID- 29186054
TI  - Implementing a Psychotherapy Service for Medically Unexplained Symptoms in a
      Primary Care Setting.
AB  - Medically unexplained symptoms (MUS) are known to be costly, complex to manage
      and inadequately addressed in primary care settings. In many cases, there are
      unresolved psychological and emotional processes underlying these symptoms,
      leaving traditional medical approaches insufficient. This paper details the
      implementation of an evidence-based, emotion-focused psychotherapy service for
      MUS across two family medicine clinics. The theory and evidence-base for using
      Intensive Short-Term Dynamic Psychotherapy (ISTDP) with MUS is presented along
      with the key service components of assessment, treatment, education and research.
      Preliminary outcome indicators showed diverse benefits. Patients reported
      significantly decreased somatic symptoms in the Patient Health Questionnaire-15
      (d = 0.4). A statistically significant (23%) decrease in family physicians'
      visits was found in the 6 months after attending the MUS service compared to the
      6 months prior. Both patients and primary care clinicians reported a high degree
      of satisfaction with the service. Whilst further research is needed, these
      findings suggest that a direct psychology service maintained within the family
      practice clinic may assist patient and clinician function while reducing
      healthcare utilization. Challenges and further service developments are
      discussed, including the potential benefits of re-branding the service to become
      a 'Primary Care Psychological Consultation and Treatment Service'.

PMID- 29186055
TI  - Methods for Involving Older People in Health Research-A Review of the Literature.
AB  - Demographic change has increased the need for research on healthcare for older
      people. Recently there has been a growing awareness that research might benefit
      from actively involving patients and the public in study design and conduct.
      Besides empowering patients and democratizing research, involvement enhances the
      quality of research and the development of equitable healthcare solutions. Little
      is known about how to involve older people. This review aims to support
      scientists intending to involve older people in health research by systematically
      identifying and describing studies involving older people and analyzing
      associated facilitators and challenges. Old people were operationalized as people
      living with old-age-related conditions. We conducted a systematic search in
      PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and
      Cochrane library for the period 2007 to July 2017 and also manually searched
      reference lists of the nine retrieved articles and other relevant sources. While
      involvement of older people in research is feasible, specific challenges related
      to this group need be taken into account. Strategies to enhance effective
      involvement comprise a thoughtful choice of location, use of visualization and
      accessible communication, building good relationships and flexible approaches.
      Further research is needed on the involvement of people in care homes or with
      vision, hearing or mobility limitations.

PMID- 29186057
TI  - Development of Spectral Disease Indices for 'Flavescence Doree' Grapevine Disease
      Identification.
AB  - Spectral measurements are employed in many precision agriculture applications,
      due to their ability to monitor the vegetation's health state. Spectral
      vegetation indices are one of the main techniques currently used in remote
      sensing activities, since they are related to biophysical and biochemical crop
      variables. Moreover, they have been evaluated in some studies as potentially
      beneficial for detecting or differentiating crop diseases. Flavescence Doree (FD)
      is an infectious, incurable disease of the grapevine that can produce severe
      yield losses and, hence, compromise the stability of the vineyards. The aim of
      this study was to develop specific spectral disease indices (SDIs) for the
      detection of FD disease in grapevines. Spectral signatures of healthy and
      diseased grapevine leaves were measured with a non-imaging spectro-radiometer at
      two infection severity levels. The most discriminating wavelengths were selected
      by a genetic algorithm (GA) feature selection tool, the Spectral Disease Indices
      (SDIs) are designed by exhaustively testing all possible combinations of
      wavelengths chosen. The best weighted combination of a single wavelength and a
      normalized difference is chosen to create the index. The SDIs are tested for
      their ability to differentiate healthy from diseased vine leaves and they are
      compared to some common set of Spectral Vegetation Indices (SVIs). It was
      demonstrated that using vegetation indices was, in general, better than using
      complete spectral data and that SDIs specifically designed for FD performed
      better than traditional SVIs in most of cases. The precision of the
      classification is higher than 90%. This study demonstrates that SDIs have the
      potential to improve disease detection, identification and monitoring in
      precision agriculture applications.

PMID- 29186056
TI  - Comparison of the Binding of Reversible Inhibitors to Human Butyrylcholinesterase
      and Acetylcholinesterase: A Crystallographic, Kinetic and Calorimetric Study.
AB  - Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) hydrolyze the
      neurotransmitter acetylcholine and, thereby, function as coregulators of
      cholinergic neurotransmission. Although closely related, these enzymes display
      very different substrate specificities that only partially overlap. This
      disparity is largely due to differences in the number of aromatic residues lining
      the active site gorge, which leads to large differences in the shape of the gorge
      and potentially to distinct interactions with an individual ligand. Considerable
      structural information is available for the binding of a wide diversity of
      ligands to AChE. In contrast, structural data on the binding of reversible
      ligands to BChE are lacking. In a recent effort, an inhibitor competition
      approach was used to probe the overlap of ligand binding sites in BChE. Here, we
      extend this study by solving the crystal structures of human BChE in complex with
      five reversible ligands, namely, decamethonium, thioflavin T, propidium, huprine,
      and ethopropazine. We compare these structures to equivalent AChE complexes when
      available in the protein data bank and supplement this comparison with kinetic
      data and observations from isothermal titration calorimetry. This new information
      now allows us to define the binding mode of various ligand families and will be
      of importance in designing specific reversible ligands of BChE that behave as
      inhibitors or reactivators.

PMID- 29186058
TI  - A Real-Time Robust Method to Detect BeiDou GEO/IGSO Orbital Maneuvers.
AB  - The frequent maneuvering of BeiDou Geostationary Orbit (GEO) and Inclined
      Geosynchronous Orbit (IGSO) satellites affects the availability of real-time
      orbit, and decreases the accuracy and performance of positioning, navigation and
      time (PNT) services. BeiDou satellite maneuver information cannot be obtained by
      common users. BeiDou broadcast ephemeris is the only indicator of the health
      status of satellites, which are broadcast on an hourly basis, easily leading to
      ineffective observations. Sometimes, identification errors of satellite abnormity
      also appear in the broadcast ephemeris. This study presents a real-time robust
      detection method for a satellite orbital maneuver with high frequency and high
      reliability. By using the broadcast ephemeris and pseudo-range observations, the
      time discrimination factor and the satellite identification factor were defined
      and used for the real-time detection of start time and the pseudo-random noise
      code (PRN) of satellites was used for orbital maneuvers. Data from a Multi-GNSS
      Experiment (MGEX) was collected and analyzed. The results show that the start
      time and the PRN of the satellite orbital maneuver could be detected accurately
      in real time. In addition, abnormal start times and satellite abnormities caused
      by non-maneuver factors also could be detected using the proposed method. The new
      method not only improves the utilization of observations for users with the data
      effective for about 92 min, but also promotes the reliability of real-time PNT
      services.

PMID- 29186059
TI  - Effect of Gamma-Oryzanol as Therapeutic Agent to Prevent Cardiorenal Metabolic
      Syndrome in Animals Submitted to High Sugar-Fat Diet.
AB  - BACKGROUND: The high consumption of fat and sugar contributes to the development
      of obesity and co-morbidities, such as diabetes, and cardiovascular and kidney
      diseases. Different strategies have been used to prevent these diseases
      associated with obesity, such as changes in eating habits and/or the addition of
      dietary components with anti-inflammatory and anti-oxidant properties, such as
      gamma-oryzanol (gammaOz) present mainly in bran layers and rice germ. METHODS:
      Animals were randomly divided into four experimental groups and fed ad libitum
      for 20 weeks with control diet (C, n = 8), control diet + gammaOz (C + gammaOz, n
      = 8), high-sugar and high-fat diet (HSF, n = 8), and high-sugar and high-fat diet
      + gammaOz (HSF + gammaOz, n = 8). HSF groups also received water + sucrose (25%).
      The dose of gammaOz was added to diets to reach 0.5% of final concentration
      (w/w). Evaluation in animals included food and caloric intake, body weight,
      plasma glucose, insulin, triglycerides, uric acid, HOMA-IR, glomerular filtration
      rate, protein/creatinine ratio, systolic blood pressure, and Doppler
      echocardiographic. RESULTS: Animals that consumed the HSF diet had weight gain
      compared to group C, increased insulin, HOMA, glucose and triglycerides, there
      were also atrial and ventricular structural alterations, deterioration of
      systolic and diastolic function, decreased glomerular filtration rate, and
      proteinuria. Gamma-oryzanol is significantly protective against effects on body
      weight, hypertriglyceridemia, renal damage, and against structural and functional
      alteration of the heart. CONCLUSION: Gamma-oryzanol shows potential as a
      therapeutic to prevent Cardiorenal Metabolic Syndrome.

PMID- 29186060
TI  - Depth-Based Detection of Standing-Pigs in Moving Noise Environments.
AB  - In a surveillance camera environment, the detection of standing-pigs in real-time
      is an important issue towards the final goal of 24-h tracking of individual pigs.
      In this study, we focus on depth-based detection of standing-pigs with "moving
      noises", which appear every night in a commercial pig farm, but have not been
      reported yet. We first apply a spatiotemporal interpolation technique to remove
      the moving noises occurring in the depth images. Then, we detect the standing
      pigs by utilizing the undefined depth values around them. Our experimental
      results show that this method is effective for detecting standing-pigs at night,
      in terms of both cost-effectiveness (using a low-cost Kinect depth sensor) and
      accuracy (i.e., 94.47%), even with severe moving noises occluding up to half of
      an input depth image. Furthermore, without any time-consuming technique, the
      proposed method can be executed in real-time.

PMID- 29186061
TI  - Identification of Alpha and Beta Coronavirus in Wildlife Species in France: Bats,
      Rodents, Rabbits, and Hedgehogs.
AB  - Coronaviruses are closely monitored in the context of emerging diseases and, as
      illustrated with Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and
      Middle East Respiratory Syndrome-coronavirus (MERS-CoV), are known to cross the
      species barrier and eventually to move from wildlife to humans. Knowledge of the
      diversity of coronaviruses in wildlife is therefore essential to better
      understand and prevent emergence events. This study explored the presence of
      coronaviruses in four wild mammal orders in France: Bats, rodents, lagomorphs,
      and hedgehogs. Betacoronavirus and Alphacoronavirus genera were identified. The
      results obtained suggest the circulation of potentially evolving virus strains,
      with the potential to cross the species barrier.

PMID- 29186063
TI  - Structural Masquerade of Plesiomonas shigelloides Strain CNCTC 78/89 O-Antigen
      High-Resolution Magic Angle Spinning NMR Reveals the Modified d-galactan I of
      Klebsiella pneumoniae.
AB  - The high-resolution magic angle spinning nuclear magnetic resonance spectroscopy
      (HR-MAS NMR) analysis of Plesiomonas shigelloides 78/89 lipopolysaccharide
      directly on bacteria revealed the characteristic structural features of the O
      acetylated polysaccharide in the NMR spectra. The O-antigen profiles were unique,
      yet the pattern of signals in the, spectra along with their 1H,13C chemical shift
      values, resembled these of d-galactan I of Klebsiella pneumoniae. The isolated O
      specific polysaccharide (O-PS) of P. shigelloides strain CNCTC 78/89 was
      investigated by 1H and 13C NMR spectroscopy, mass spectrometry and chemical
      methods. The analyses demonstrated that the P. shigelloides 78/89 O-PS is
      composed of ->3)-alpha-d-Galp-(1->3)-beta-d-Galf2OAc-(1-> disaccharide repeating
      units. The O-acetylation was incomplete and resulted in a microheterogeneity of
      the O-antigen. This O-acetylation generates additional antigenic determinants
      within the O-antigen, forms a new chemotype, and contributes to the epitopes
      recognized by the O-serotype specific antibodies. The serological cross
      reactivities further confirmed the inter-specific structural similarity of these
      O-antigens.

PMID- 29186065
TI  - Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A
      Potential Target to Prevent Alcohol-Induced Neurodegeneration.
AB  - Excessive alcohol consumption leads to neurodegeneration, which contributes to
      cognitive decline that is associated with alcohol use disorders (AUDs). The
      endocannabinoid system has been implicated in the development of AUDs, but little
      is known about how the neurotoxic effects of alcohol impact the endocannabinoid
      system. Therefore, the current study investigated the effects of neurotoxic,
      binge-like alcohol exposure on components of the endocannabinoid system and
      related N-acylethanolamines (NAEs), and then evaluated the efficacy of fatty acid
      amide hydrolase (FAAH) inhibition on attenuating alcohol-induced
      neurodegeneration. Male rats were administered alcohol according to a binge
      model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the
      entorhinal cortex and hippocampus following two days, but not four days, of
      treatment. Furthermore, binge alcohol treatment did not change the tissue content
      of the three NAEs quantified, including the endocannabinoid and anandamide. In a
      separate study, the FAAH inhibitor, URB597 was administered to rats during
      alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB)
      staining. The administration of URB597 during binge treatment did not
      significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however,
      a follow up "target engagement" study found that NAE augmentation by URB597 was
      impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations
      in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by
      FAAH inhibition.

PMID- 29186064
TI  - Airway Mucus and Asthma: The Role of MUC5AC and MUC5B.
AB  - Asthma is characterized by mucus abnormalities. Airway epithelial hyperplasia and
      metaplasia result in changes in stored and secreted mucin and the production of a
      pathologic mucus gel. Mucus transport is impaired, culminating in mucus plugging
      and airway obstruction-a major cause of morbidity in asthma. The polymeric mucins
      MUC5AC and MUC5B are integral components of airway mucus. MUC5AC and MUC5B gene
      expression is altered in asthma, and recent work sheds light on their
      contribution to asthma pathogenesis. Herein, we review our current understanding
      of the role of MUC5AC and MUC5B in mucus dysfunction in asthma.

PMID- 29186066
TI  - An Advanced Hybrid Technique of DCS and JSRC for Telemonitoring of Multi-Sensor
      Gait Pattern.
AB  - The jointly quantitative analysis of multi-sensor gait data for the best gait
      classification performance has been a challenging endeavor in wireless body area
      networks (WBANs)-based gait telemonitoring applications. In this study, based on
      the joint sparsity of data, we proposed an advanced hybrid technique of
      distributed compressed sensing (DCS) and joint sparse representation
      classification (JSRC) for multi-sensor gait classification. Firstly, the DCS
      technique is utilized to simultaneously compress multi-sensor gait data for
      capturing spatio-temporal correlation information about gait while the energy
      efficiency of the sensors is available. Then, the jointly compressed gait data
      are directly used to develop a novel neighboring sample-based JSRC model by
      defining the sparse representation coefficients-inducing criterion (SRCC), in
      order to yield the best classification performance as well as a lower
      computational time cost. The multi-sensor gait data were selected from an open
      wearable action recognition database (WARD) to validate the feasibility of our
      proposed method. The results showed that when the comparison ratio and the number
      of neighboring samples are selected as 70% and 40%, respectively, the best
      accuracy (95%) can be reached while the lowest computational time spends only 60
      ms. Moreover, the best accuracy and the computational time can increase by 5% and
      decrease by 40 ms, respectively, when compared with the traditional JSRC
      techniques. Our proposed hybrid technique can take advantage of the joint
      sparsity of data for jointly processing multi-sensor gait data, which greatly
      contributes to the best gait-classification performance. This has great potential
      for energy-efficient telemonitoring of multi-sensor gait.

PMID- 29186067
TI  - Immunohistochemical Characterization of Connexin43 Expression in a Mouse Model of
      Diabetic Retinopathy and in Human Donor Retinas.
AB  - Diabetic retinopathy (DR) develops due to hyperglycemia and inflammation-induced
      vascular disruptions in the retina with connexin43 expression patterns in the
      disease still debated. Here, the effects of hyperglycemia and inflammation on
      connexin43 expression in vitro in a mouse model of DR and in human donor tissues
      were evaluated. Primary human retinal microvascular endothelial cells (hRMECs)
      were exposed to high glucose (HG; 25 mM) or pro-inflammatory cytokines IL-1beta
      and TNF-alpha (10 ng/mL each) or both before assessing connexin43 expression.
      Additionally, connexin43, glial fibrillary acidic protein (GFAP), and plasmalemma
      vesicular associated protein (PLVAP) were labeled in wild-type (C57BL/6), Akita
      (diabetic), and Akimba (DR) mouse retinas. Finally, connexin43 and GFAP
      expression in donor retinas with confirmed DR was compared to age-matched
      controls. Co-application of HG and cytokines increased connexin43 expression in
      hRMECs in line with results seen in mice, with no significant difference in
      connexin43 or GFAP expression in Akita but higher expression in Akimba compared
      to wild-type mice. On PLVAP-positive vessels, connexin43 was higher in Akimba but
      unchanged in Akita compared to wild-type mice. Connexin43 expression appeared
      higher in donor retinas with confirmed DR compared to age-matched controls,
      similar to the distribution seen in Akimba mice and correlating with the in vitro
      results. Although connexin43 expression seems reduced in diabetes, hyperglycemia
      and inflammation present in the pathology of DR seem to increase connexin43
      expression, suggesting a causal role of connexin43 channels in the disease
      progression.

PMID- 29186068
TI  - Study of Structure and Permeability Relationship of Flavonoids in Caco-2 Cells.
AB  - Flavonoids exhibit a broad range of biological activities. However, poor
      absorption of some flavonoids is a major limitation for use of flavonoids as
      nutraceuticals. To investigate the structure requirements for flavonoids
      intestinal absorption, transepithelial transport and cellular accumulation (CA)
      of 30 flavonoids were determined using the Caco-2 cell monolayer. The bilateral
      permeation of five types of flavonoids followed the order: flavanones >=
      isoflavones > flavones >= chalcones > flavonols. The concentration of flavonoids
      accumulated in cells did not correlate with cell penetration since the
      correlation coefficient between the apparent permeability coefficient (Papp) and
      their corresponding CA was poor (R2 < 0.3). Most flavonoids exhibited a ratio of
      0.8-1.5 for Papp A to B/Papp B to A, suggesting passive diffusion pathways.
      However, luteolin, morin and taxifolin may involve the efflux mechanisms. The
      quantitative structure-permeability relationship (QSPR) study demonstrated that
      the intestinal absorption of flavonoids can be related to atomic charges on
      carbon 3' (QC3'), molecule surface area (SlogP_V3), balance between the center of
      mass and position of hydrophobic region (vsurf_ID1) and solvation energy of
      flavonoids (E_sol). These results provide useful information for initially
      screening of flavonoids with high intestinal absorption.

PMID- 29186070
TI  - Psychology of the Embrace: How Body Rhythms Communicate the Need to Indulge or
      Separate.
AB  - In the context of embodiment research, there has been a growing interest in
      phenomena of interpersonal resonance. Given that haptic communication is
      particularly under-researched, we focused on the phenomenon of embracing. When we
      embrace a dear friend to say good-bye at the end of a great evening, we typically
      first employ smooth and yielding movements with round transitions between
      muscular tensing and relaxing (smooth, indulging rhythms), and when the embrace
      is getting too long, we start to use slight patting (sharp, fighting rhythms with
      sharp transitions) on the back or the shoulders of the partner in order to
      indicate that we now want to end the embrace. On the ground of interpersonal
      resonance, most persons (per-sonare, latin = to sound through) understand these
      implicit nonverbal signals, expressed in haptic tension-flow changes, and will
      react accordingly. To experimentally test the hypothesis that smooth, indulgent
      rhythms signal the wish to continue, and sharp, fighting rhythms signal the wish
      to separate from an embrace, we randomly assigned 64 participants, all students
      at the University of Heidelberg, to two differently sequenced embrace conditions:
      (a) with the fighting rhythm at the end of the sequence of two indulgent rhythms
      (Sequence A: smooth-smooth-sharp); and (b) with the fighting rhythm between two
      indulgent rhythms (Sequence B: smooth-sharp-smooth). Participants were embraced
      for 30 s by a female confe-derate with their eyes blindfolded to focus on haptic
      and kinesthetic cues without being distracted by visual cues. They were
      instructed to let go of a handkerchief that they held between the fingers of
      their dominant hand during the embrace, when they felt that the embracer signaled
      the wish to finish the embrace. Participants significantly more often dropped the
      handkerchief in the phase of the fighting rhythm, no matter in which location it
      occurred in the embrace sequence. We assume that we learn such rhythmic behaviors
      and their meaning from the beginning of life in the communication with caregivers
      and meaningful others. Some are universal and some are quite idiosyncratic.
      Infants seem to be highly sensitive to the dynamic nuances presented to them,
      demonstrating a high capacity for embodied resonance and a high behavioral
      plasticity. Such adaptive mechanisms are assumed to lay the foundations of family
      culture (including the degree to which nonverbal cues are attended to, the
      communication of taboos, etc.) and larger culture, and may also play an important
      role in interpersonal attraction and aesthetic experience.

PMID- 29186062
TI  - Viral Oncology: Molecular Biology and Pathogenesis.
AB  - Oncoviruses are implicated in approximately 12% of all human cancers. A large
      number of the world's population harbors at least one of these oncoviruses, but
      only a small proportion of these individuals go on to develop cancer. The
      interplay between host and viral factors is a complex process that works together
      to create a microenvironment conducive to oncogenesis. In this review, the
      molecular biology and oncogenic pathways of established human oncoviruses will be
      discussed. Currently, there are seven recognized human oncoviruses, which include
      Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), Hepatitis B and C viruses
      (HBV and HCV), Human T-cell lymphotropic virus-1 (HTLV-1), Human Herpesvirus-8
      (HHV-8), and Merkel Cell Polyomavirus (MCPyV). Available and emerging therapies
      for these oncoviruses will be mentioned.

PMID- 29186069
TI  - Risk Assessment and Source Identification of 17 Metals and Metalloids on Soils
      from the Half-Century Old Tungsten Mining Areas in Lianhuashan, Southern China.
AB  - Background: Mining activities always emit metal(loid)s into the surrounding
      environment, where their accumulation in the soil may pose risks and hazards to
      humans and ecosystems. Objective: This paper aims to determine of the type,
      source, chemical form, fate and transport, and accurate risk assessment of 17
      metal(loid) contaminants including As, Cd, Cu, Ni, Pb, Zn, Cr, Ag, B, Bi, Co, Mo,
      Sb, Ti, V, W and Sn in the soils collected from an abandoned tungsten mining
      area, and to guide the implementing of appropriate remediation strategies.
      Methods: Contamination factors (CFs) and integrated pollution indexes (IPIs) and
      enrichment factors (EFs) were used to assess their ecological risk and the
      sources were identified by using multivariate statistics analysis, spatial
      distribution investigation and correlation matrix. Results: The IPI and EF values
      indicated the soils in the mine site and the closest downstream one were
      extremely disturbed by metal(loid)s such as As, Bi, W, B, Cu, Pb and Sn, which
      were emitted from the mining wastes and acid drainages and delivered by the
      runoff and human activities. Arsenic contamination was detected in nine sites
      with the highest CF values at 24.70 next to the mining site. The Cd contamination
      scattered in the paddy soils around the resident areas with higher fraction of
      bioavailable forms, primarily associated with intense application of phosphorus
      fertilizer. The lithogenic elements V, Ti, Ag, Ni, Sb, Mo exhibit low
      contamination in all sampling points and their distribution were depended on the
      soil texture and pedogenesis process. Conclusions: The long term historical
      mining activities have caused severe As contamination and higher enrichment of
      the other elements of orebody in the local soils. The appropriate remediation
      treatment approach should be proposed to reduce the bioavailability of Cd in the
      paddy soils and to immobilize As to reclaim the soils around the mining site.
      Furthermore, alternative fertilizing way and irrigating water sources are
      urgencies to reduce the input of Cd and As into the local soils effectively.

PMID- 29186071
TI  - Volasertib Enhances Sensitivity to TRAIL in Renal Carcinoma Caki Cells through
      Downregulation of c-FLIP Expression.
AB  - Polo-like kinase 1 (PLK1) plays major roles in cell cycle control and DNA damage
      response. Therefore, PLK1 has been investigated as a target for cancer therapy.
      Volasertib is the second-in class dihydropteridinone derivate that is a specific
      PLK1 inhibitor. In this study, we examined that combining PLK1 inhibitor with
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) would have an
      additive and synergistic effect on induction of apoptosis in cancer cells. We
      found that volasertib alone and TRAIL alone had no effect on apoptosis, but the
      combined treatment of volasertib and TRAIL markedly induced apoptosis in Caki
      (renal carcinoma), A498 (renal carcinoma) and A549 (lung carcinoma) cells, but
      not in normal cells (human skin fibroblast cells and mesangial cells). Combined
      treatment induced accumulation of sub-G1 phase, DNA fragmentation, cleavage of
      poly (ADP-ribose) polymerase (PARP) and activation of caspase 3 activity in Caki
      cells. Interestingly, combined treatment induced downregulation of cellular-FLICE
      inhibitory protein (c-FLIP) expression and ectopic expression of c-FLIP markedly
      blocked combined treatment-induced apoptosis. Therefore, this study demonstrates
      that volasertib may sensitize TRAIL-induced apoptosis in Caki cells via
      downregulation of c-FLIP.

PMID- 29186072
TI  - A Dependable Localization Algorithm for Survivable Belt-Type Sensor Networks.
AB  - As the key element, sensor networks are widely investigated by the Internet of
      Things (IoT) community. When massive numbers of devices are well connected,
      malicious attackers may deliberately propagate fake position information to
      confuse the ordinary users and lower the network survivability in belt-type
      situation. However, most existing positioning solutions only focus on the
      algorithm accuracy and do not consider any security aspects. In this paper, we
      propose a comprehensive scheme for node localization protection, which aims to
      improve the energy-efficient, reliability and accuracy. To handle the unbalanced
      resource consumption, a node deployment mechanism is presented to satisfy the
      energy balancing strategy in resource-constrained scenarios. According to
      cooperation localization theory and network connection property, the parameter
      estimation model is established. To achieve reliable estimations and eliminate
      large errors, an improved localization algorithm is created based on modified
      average hop distances. In order to further improve the algorithms, the node
      positioning accuracy is enhanced by using the steepest descent method. The
      experimental simulations illustrate the performance of new scheme can meet the
      previous targets. The results also demonstrate that it improves the belt-type
      sensor networks' survivability, in terms of anti-interference, network energy
      saving, etc.

PMID- 29186073
TI  - Evaluation of Inulin Replacing Chitosan in a Polyurethane/Polysaccharide Material
      for Pb2+ Removal.
AB  - Downstream waste from industry and other industrial processes could increase
      concentration of heavy metals in water. These pollutants are commonly removed by
      adsorption because it is an effective and economical method. Previously, we
      reported adsorption capacity of a chitosan/polyurethane/titanium dioxide (TiO2)
      composite for three ions in a dynamic wastewater system. There, increasing the
      chitosan concentration in composite increased the cation removal as well;
      however, for ratios higher than 50% of chitosan/TiO2, the manufacturing cost
      increased significantly. In this work, we address the manufacturing cost problem
      by proposing a new formulation of the composite. Our hypothesis is that inulin
      could replace chitosan in the composite formulation, either wholly or in part. In
      this exploratory research, three blends were prepared with a polyurethane matrix
      using inulin or/and chitosan. Adsorption was evaluated using a colorimetric
      method and the Langmuir and Freundlich models. Fourier-transform infrared
      spectroscopy (FTIR) spectra, scanning electron microscopy (SEM) micrographs,
      differential scanning calorimetry and thermogravimetric analysis curves were
      obtained to characterize blends. Results indicate that blends are suitable for
      toxic materials removal (specifically lead II, Pb2+). Material characterization
      indicates that polysaccharides were distributed in polyurethane's external part,
      thus improving adsorption. Thermal degradation of materials was found above 200 
      degrees C. Comparing the blends data, inulin could replace chitosan in part and
      thereby improve the cost efficiency and scalability of the production process of
      the polyurethane based-adsorbent. Further research with different inulin/chitosan
      ratios in the adsorbent and experiments with a dynamic system are justified.

PMID- 29186075
TI  - An Adaptive S-Method to Analyze Micro-Doppler Signals for Human Activity
      Classification.
AB  - In this paper, we propose the multiwindow Adaptive S-method (AS-method)
      distribution approach used in the time-frequency analysis for radar signals.
      Based on the results of orthogonal Hermite functions that have good time
      frequency resolution, we vary the length of window to suppress the oscillating
      component caused by cross-terms. This method can bring a better compromise in the
      auto-terms concentration and cross-terms suppressing, which contributes to the
      multi-component signal separation. Finally, the effective micro signal is
      extracted by threshold segmentation and envelope extraction. To verify the
      proposed method, six states of motion are separated by a classifier of a support
      vector machine (SVM) trained to the extracted features. The trained SVM can
      detect a human subject with an accuracy of 95.4% for two cases without
      interference.

PMID- 29186074
TI  - The Eukaryotic Elongation Factor 1 Alpha (eEF1alpha) from the Parasite Leishmania
      infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine
      (PC).
AB  - Proteins and glycolipids have been found to be decorated with phosphorylcholine
      (PC) both in protozoa and nematodes that parasitize humans and animals. PC
      epitopes can provoke various effects on immune cells leading to an
      immunomodulation of the host's immune system that allows long-term persistence of
      the parasites. So far, only a limited number of PC-modified proteins, mainly from
      nematodes, have been identified. Infections caused by Leishmania spp. (e.g., L.
      infantum in southern Europe) affect about 12 million people worldwide and are
      characterized by a wide spectrum of clinical forms in humans, ranging from
      cutaneous to fatal visceral leishmaniasis. To establish and maintain the
      infection, these protozoa are dependent on the secretion of effector molecules
      into the host for modulating their immune system. In this project, we analyzed
      the PC modification of L. infantum promastigotes by 2D-gel based proteomics.
      Western blot analysis with the PC-specific antibody TEPC-15 revealed one PC
      substituted protein in this organism, identified as eEF1alpha. We could
      demonstrate that the binding of eEF1alpha to one of its downstream effectors is
      dependent on its PC-modification. In this study we provide evidence that in this
      parasite the modification of eEF1alpha with PC may be essential for its function
      as an important virulence factor.

PMID- 29186076
TI  - The Role of Anti-Thymocyte Globulin or Alemtuzumab-Based Serotherapy in the
      Prophylaxis and Management of Graft-Versus-Host Disease.
AB  - Allogeneic hematopoietic stem cell transplant is an established treatment
      modality for hematologic and non-hematologic diseases. However, it is associated
      with acute and long-term sequelae which can translate into mortality. Graft
      versus-host disease (GVHD) remains a glaring obstacle, especially with the advent
      of reduced-intensity conditioning. Serotherapy capitalizes on antibodies which
      target T cells and other immune cells to mitigate this effect. This article
      focuses on the utility of two such agents: anti-thymocyte globulin (ATG) and
      alemtuzumab. ATG has demonstrated benefit in prophylaxis against GVHD, especially
      in the chronic presentation. However, there is limited impact of ATG on overall
      survival and it has little utility in the treatment context. There may be an
      initial improvement, particularly in skin manifestations, but no substantial
      benefit has been elicited. Alemtuzumab has shown benefit in both prophylaxis and
      treatment of GVHD, but at the consequence of a more profound immunosuppressive
      phase, mandating aggressive viral prophylaxis. There remains heterogeneity in the
      doses and regimens of the agents, with no standardized protocol in place.
      Furthermore, it seems that once steroid-refractory GVHD has been established,
      there is little that can be offered to offset the ultimately dismal outcome. Here
      we present a systematic overview of ATG- or alemtuzumab-based serotherapy in the
      prophylaxis and management of GVHD.

PMID- 29186078
TI  - Biological Properties of Low-Toxicity PLGA and PLGA/PHB Fibrous Nanocomposite
      Implants for Osseous Tissue Regeneration. Part I: Evaluation of Potential
      Biotoxicity.
AB  - In response to the demand for new implant materials characterized by high
      biocompatibility and bioresorption, two prototypes of fibrous nanocomposite
      implants for osseous tissue regeneration made of a newly developed blend of
      poly(l-lactide-co-glycolide) (PLGA) and syntheticpoly([R,S]-3-hydroxybutyrate),
      PLGA/PHB, have been developed and fabricated. Afibre-forming copolymer of
      glycolide and l-lactide (PLGA) was obtained by a unique method of synthesis
      carried out in blocksusing Zr(AcAc)4 as an initiator. The prototypes of the
      implants are composed of three layers of PLGA or PLGA/PHB, nonwoven fabrics with
      a pore structure designed to provide the best conditions for the cell
      proliferation. The bioactivity of the proposed implants has been imparted by
      introducing a hydroxyapatite material and IGF1, a growth factor. The developed
      prototypes of implants have been subjected to a set of in vitro and in
      vivobiocompatibility tests: in vitro cytotoxic effect, in vitro genotoxicity and
      systemic toxicity. Rabbitsshowed no signs of negative reactionafter implantation
      of the experimental implant prototypes.

PMID- 29186079
TI  - Assessment of Embedded Conjugated Polymer Sensor Arrays for Potential Load
      Transmission Measurement in Orthopaedic Implants.
AB  - Load transfer through orthopaedic joint implants is poorly understood. The longer
      term outcomes of these implants are just starting to be studied, making it
      imperative to monitor contact loads across the entire joint implant interface to
      elucidate the force transmission and distribution mechanisms exhibited by these
      implants in service. This study proposes and demonstrates the design,
      implementation, and characterization of a 3D-printed smart polymer sensor array
      using conductive polyaniline (PANI) structures embedded within a polymeric parent
      phase. The piezoresistive characteristics of PANI were investigated to
      characterize the sensing behaviour inherent to these embedded pressure sensor
      arrays, including the experimental determination of the stable response of PANI
      to continuous loading, stability throughout the course of loading and unloading
      cycles, and finally sensor repeatability and linearity in response to incremental
      loading cycles. This specially developed multi-material additive manufacturing
      process for PANI is shown be an attractive approach for the fabrication of
      implant components having embedded smart-polymer sensors, which could ultimately
      be employed for the measurement and analysis of joint loads in orthopaedic
      implants for in vitro testing.

PMID- 29186080
TI  - E2mC: Improving Emergency Management Service Practice through Social Media and
      Crowdsourcing Analysis in Near Real Time.
AB  - In the first hours of a disaster, up-to-date information about the area of
      interest is crucial for effective disaster management. However, due to the delay
      induced by collecting and analysing satellite imagery, disaster management
      systems like the Copernicus Emergency Management Service (EMS) are currently not
      able to provide information products until up to 48-72 h after a disaster event
      has occurred. While satellite imagery is still a valuable source for disaster
      management, information products can be improved through complementing them with
      user-generated data like social media posts or crowdsourced data. The advantage
      of these new kinds of data is that they are continuously produced in a timely
      fashion because users actively participate throughout an event and share related
      information. The research project Evolution of Emergency Copernicus services
      (E2mC) aims to integrate these novel data into a new EMS service component called
      Witness, which is presented in this paper. Like this, the timeliness and accuracy
      of geospatial information products provided to civil protection authorities can
      be improved through leveraging user-generated data. This paper sketches the
      developed system architecture, describes applicable scenarios and presents
      several preliminary case studies, providing evidence that the scientific and
      operational goals have been achieved.

PMID- 29186081
TI  - Properties-Adjustable Alumina-Zirconia Nanolaminate Dielectric Fabricated by Spin
      Coating.
AB  - In this paper, an alumina-zirconia (Al2O3-ZrO2) nanolaminate dielectric was
      fabricated by spin-coating and the performance was investigated. It was found
      that the properties of the dielectric can be adjusted by changing the content of
      Al2O3/ZrO2 in nanolaminates: when the content of Al2O3 was higher than 50%, the
      properties of nanolaminates, such as the optical energy gap, dielectric strength
      (Vds), capacitance density, and relative permittivity were relatively stable,
      while the change of these properties became larger when the content of Al2O3 was
      less than 50%. With the content of ZrO2 varying from 50% to 100%, the variation
      of these properties was up to 0.482 eV, 2.12 MV/cm, 135.35 nF/cm2, and 11.64,
      respectively. Furthermore, it was demonstrated that the dielectric strength of
      nanolaminates were influenced significantly by the number (n) of bilayers. Every
      increment of one Al2O3-ZrO2 bilayer will enhance the dielectric strength by
      around 0.39 MV/cm (Vds ~ 0.86 + 0.39n). This could be contributed to the
      amorphous alumina which interrupted the grain boundaries of zirconia.

PMID- 29186082
TI  - Shingrix--an adjuvanted, recombinant herpes zoster vaccine.

PMID- 29186083
TI  - Naldemedine (Symproic) for opioid-induced constipation.

PMID- 29186084
TI  - Extended-release amantadine (Gocovri) for dyskinesia in Parkinson's disease.

PMID- 29186085
TI  - PARP inhibitors for ovarian cancer.

PMID- 29186086
TI  - In brief: New hypertension guidelines.

PMID- 29186077
TI  - Telomeres, Aging and Exercise: Guilty by Association?
AB  - Telomeres are repetitive tandem DNA sequences that cap chromosomal ends
      protecting genomic DNA from enzymatic degradation. Telomeres progressively
      shorten with cellular replication and are therefore assumed to correlate with
      biological and chronological age. An expanding body of evidence suggests (i) a
      predictable inverse association between telomere length, aging and age-related
      diseases and (ii) a positive association between physical activity and telomere
      length. Both hypotheses have garnered tremendous research attention and broad
      consensus; however, the evidence for each proposition is inconsistent and
      equivocal at best. Telomere length does not meet the basic criteria for an aging
      biomarker and at least 50% of key studies fail to find associations with physical
      activity. In this review, we address the evidence in support and refutation of
      the putative associations between telomere length, aging and physical activity.
      We finish with a brief review of plausible mechanisms and potential future
      research directions.

PMID- 29186087
TI  - Three more immune checkpoint inhibitors for advanced bladder cancer.

PMID- 29186088
TI  - Giant Cell (Temporal) Arteritis with Persistent Bilateral Sensorineural Hearing
      Loss - A Likely Consequence of Delayed Institution of Glucocorticoid Therapy.

PMID- 29186089
TI  - Correlation Between Methylenetetrahydrofolate Reductase (MTHFR) C677T
      Polymorphisms and Pemetrexed Chemotherapy Efficacy/Toxicity in Non-Squamous Non
      Small Cell Lung Cancer.
AB  - BACKGROUND In the present study, we aimed to retrospectively analyze the
      correlation between toxicity of pemetrexed (PEM) chemotherapy and
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms in patients with
      advanced non-squamous non-small cell lung cancer (non-sq NSCLC). MATERIAL AND
      METHODS We used polymerase chain reaction, gene scanning, and restriction
      fragment length polymorphism to analyze MTHFR C677T in 51 patients with advanced
      non-sq NSCLC. The patients received chemotherapies with single-agent PEM
      (monotherapy group) or with PEM combined with cisplatin (joint group). The
      correlation between MTHFR C677T polymorphisms and chemotherapy efficacy/toxicity
      was also assessed. RESULTS There were 40 patients in the monotherapy group and 11
      patients in the joint group. Among the 40 patients received single-agent PEM
      chemotherapy, those with the CT/TT genotype had higher incidence of leukopenia,
      neutropenia, nausea, and fatigue compared to patients with the with wild-type
      genotype CC (all P<0.05). However, polymorphisms of MTHFR C677T were not
      significantly associated with other adverse events and clinical outcomes.
      CONCLUSIONS Compared with genotype CC (the wild type), patients with the CT/TT
      genotype had higher incidence of leukopenia, neutropenia, nausea, and fatigue.
      Therefore, the MTHFR C677T polymorphism could be a predictive factor for
      leukopenia, neutropenia, nausea, and fatigue toxicities in non-sq NSCLC patients
      treated with single-agent PEM.

PMID- 29186090
TI  - [Comparative analysis of the effectiveness of various techniques of endoscopic
      prostate enucleation in a single center].
AB  - AIM: To compare electro- and laser enucleation (thulium, holmium) of prostate
      hyperplasia. MATERIAL AND METHODS: 693 prostate hyperplasia patients were
      enrolled. 489 patients underwent holmium enucleation (HoLEP), 51 - monopolar
      enucleation, 153 - thulium enucleation (ThuLEP). Prostate volume was 91.7 (50
      250) cm3. There were no significant differences in preoperative variables between
      both groups (I-PSS, QoL, Qmax, residual urine volume) (p>0.05). RESULTS: Mean
      time of HoLEP was 97.0+/-42.2 min, monopolar enucleation - 112.9+/-36.3 min,
      ThuLEP duration was significantly less (77.4+/-36.3 min, p<0.01). An efficacy of
      all methods was confirmed in 6 months after surgery by significant (p<0.01)
      improvement of functional parameters (I-PSS, QoL, Qmax, residual urine volume).
      CONCLUSION: High efficiency of thulium and holmium enucleation allows to consider
      them as 'gold standard' of prostate hyperplasia management. Despite higher
      incidence of complications an efficacy of monopolar enucleation is comparable to
      that in laser techniques.

PMID- 29186091
TI  - [Managerial and methodological aspects of emergency surgery for malignant colonic
      obstruction].
AB  - AIM: To determine the most feasible treatment strategy for malignant colonic
      obstruction. MATERIAL AND METHODS: There were 427 patients with malignant colonic
      obstruction who were hospitalized for emergency indications. 30 of them were
      treated with medical therapy; 286 - underwent acute resection; 43 - stoma
      construction; 68 - stents deployment. 64 out of 427 patients underwent elective
      restorative/radical surgery and radio- or chemotherapy in 1-8 months. 3-year
      Kaplan-Meier survival was assessed. RESULTS: Complications occurred in 58% after
      acute resection and in 32.6% and 8.8% after stoma and stent deployment,
      respectively. Postoperative mortality was significantly lower after palliative
      surgery (stent or stoma) compared with acute resection: 2.9%, 18.6%, 29.37%,
      respectively. 3-year survival was higher after elective resections compared with
      emergency resection group: 0,81 i 0,68 respectively. CONCLUSION: Bridging
      strategy (stoma/stents) may be a valid alternative in some patients with
      malignant colonic obstruction due to significantly reduced postoperative
      mortality. Acute surgery for malignant colonic obstruction should only be carried
      out by appropriately trained surgeons at multi-field hospital.

PMID- 29186093
TI  - [Rehbein procedure for secondary megacolon in children].
AB  - AIM: To evaluate the results of Rehbein procedure with extraperitoneal colorectal
      anastomosis combined with complex conservative treatment in children with
      secondary megacolon due to chronic constipation. MATERIAL AND METHODS: We carried
      out surgical interventions in 78 children aged 7-12 years with chronic colostasis
      resistant to conservative treatment. All patients underwent clinical, laboratory
      and instrumental examination. All patients were divided into 3 groups depending
      on type of surgery: group I - colon resection followed by intraperitoneal
      colorectal anastomosis (28 patients), group II - open Rehbein procedure (29
      patients), group III - laparoscopic Rehbein procedure (21 patients). RESULTS:
      Absence of dyspeptic disorders and enterocolitis in remote postoperative period
      in patients receiving comprehensive treatment enhanced with new additions is the
      cause of improved outcomes. Type of surgery should be individualized in view of
      anatomical colon changes and secondary pathological conditions. Some pathological
      symptoms observed at preoperative period may be recurrent in long-term
      postoperative period due to wrong selection of surgery. The risk of recurrent
      chronic constipation is high after colon resection followed by intraperitoneal
      colorectal anastomosis. CONCLUSION: Rehbein procedure may be preferred for
      management of secondary megarectum and megasigma. Laparoscopic technique reduces
      surgical trauma and requires less postoperative analgesia.

PMID- 29186092
TI  - [Emergency endoscopic surgery of colon cancer].
AB  - AIM: To assess the role of endoscopic technologies in treatment of complicated
      forms of colorectal cancer. MATERIAL AND METHODS: Our trial included patients
      after endoscopic intervention (n=18) and open surgery (n=11). RESULTS: Mean time
      of surgery in this group was 158.8+/-10.7 minutes. In elective surgery group this
      value was 161.3 minutes (p>0.05). Mean blood loss was not great (near 122.5+/
      17.9 ml). Overall and postoperative hospital-stay was 23.1+/-2.4 and 8.6+/-0.5
      days, respectively. There were no intraoperative and postoperative complications.
      CONCLUSION: Endoscopic interventions may be performed for colon cancer for
      emergency indications including patients with severe complications.

PMID- 29186094
TI  - [Pectoral-retroauricular approach for endoscopic parathyroidectomy (experimental
      study)].
AB  - AIM: To develop and investigate in the experiment the method of endoscopic
      parathyroidectomy in order to prevent intraoperative 'conflict of the
      instruments' and to reduce surgical trauma via extracervical approach. MATERIAL
      AND METHODS: The results of 10 experimental endoscopic parathyroidectomies with
      original pectoral-retroauricular approach were analyzed. RESULTS: Mean time of
      surgery was 77.8+/-10.2 minutes (65-97), mean time of surgical exposure - 50.3+/
      6.7 minutes (41-59). Visualization and identification of parathyroid glands were
      achieved in 100% of cases. Recurrent laryngeal nerve was preserved in 100% of
      cases. CONCLUSION: Original endoscopic pectoral-retroauricular approach for
      parathyroidectomy is methodologically and technically justified and can be
      recommended for clinical application.

PMID- 29186095
TI  - [Intraoperative fluid therapy during esophagectomy followed by repair].
AB  - AIM: To optimize fluid therapy in transhiatal eshophagectomy by using of goal
      oriented infusion therapy based on stroke volume variation. MATERIAL AND METHODS:
      Our trial enrolled 30 patients who underwent transhiatal esophagectomy followed
      by repair for the period 2011-2014. Patients were divided into 2 groups. The
      first group (LT) included 16 patients with liberal fluid therapy. The second
      group (GDT) consisted of 14 patients in whom goal-oriented fluid therapy was
      performed. Goal-oriented fluid therapy was implemented via stroke volume
      variation (SVV). RESULTS: Infusion rate was 6.7 ml/kg/h and 11.5 ml/kg/h in the
      main and control groups, respectively. Morbidity rate was 28.6% (n=4) and 62.5%
      (n=10) in the main and control groups respectively. Clavien-Dindo IV
      complications were lung atelectasis (n=2, 14%), pneumonia (n=1, 7%). Hydrothorax
      required puncture was noted in 1 (7%) case. Acute respiratory failure as
      complication IVa was in 1 (9%) patient. In the control group complications were
      registered in 10 (62.5%) patients. Complications I-II degree included lung
      atelectasis (n=4, 25%), cervical anastomosis failure (n=1, 6%); complications IVa
      were observed in 8 cases (50%). It was significant respiratory failure with
      reduced PO2/FiO2<300. Patients of the main group required less time for
      postoperative mechanical ventilation (120 [90-300] vs. 315 [215-810] min (p=0.02)
      and ICU-stay (0.83 [0.7-0.8] vs. 1.75 [1.25-2.75] (p=0.0022).

PMID- 29186096
TI  - [Local injection therapy of damage of paraarticular tissue].
AB  - AIM: To evaluate the potential of local injection therapy with Alflutop in
      management of paraarticular tissue lesions (PTL). MATERIAL AND METHODS: 44
      patients with various localization of PTL were examined and exposed to treatment.
      RESULTS: As a result of local therapy with Alflutop, the majority of patients
      with PTL experienced a decrease in pain syndrome and an increase in the
      functional capabilities. There was no negative dynamic of symptoms. CONCLUSION:
      Treatment with Alflutop was well tolerated by patients, easily applied, had a
      small number of side effects and was accompanied by a pronounced clinical effect.

PMID- 29186098
TI  - [How do I do it: aortic valve replacement].

PMID- 29186097
TI  - [The experience of the using Tolperisone in a complex conservative therapy of an
      osteoarthrosis of a hip joint].
AB  - AIM: The comparison of the efficiency of the standard scheme of a conservative
      medicinal therapy of an OA of a hip joint and the modified scheme (with the
      muscle relaxant of the central action - Tolperisone) was the research objective.
      MATERIAL AND METHODS: The prospective research of the complex conservative
      therapy of two pools of patients with initial stages of a coxarthrosis from 2014
      for 2017 with the subject assessment articulary treatment components is
      conducted. RESULTS: As a result of the studying of the clinical performance of
      the modified scheme in comparison with the standard scheme of the therapy at
      patients with the prevalence of an arthritic component of a disease established
      the best results of the therapy.

PMID- 29186099
TI  - [Simple and reliable pancreatoenteroanastomosis].

PMID- 29186100
TI  - [Simultaneous Bentall-de-Bono procedure and descending thoracic aortic bypass
      through median sternotomy].

PMID- 29186101
TI  - [Mid-term results of hybrid treatment of aortic dissection combined with
      Kommerell's diverticulum].

PMID- 29186102
TI  - [Sternomediastinitis after cardiac transplantation].

PMID- 29186103
TI  - [Left hemihepatectomy with thrombectomy from inferior vena cava and right atrium
      under cardiopulmonary bypass in patient with hepatocellular carcinoma].

PMID- 29186104
TI  - [Portal cholangiocarcinoma: epidemiology, staging principles and aspects of tumor
      biology].

PMID- 29186105
TI  - [Comparative analysis of colorectal cancer screening approaches].

PMID- 29186106
TI  - Late preterm prelabor rupture of fetal membranes: fetal inflammatory response and
      neonatal outcome.
AB  - BackgroundTo characterize the influence of microbial invasion of the amniotic
      cavity (MIAC) and/or intra-amniotic inflammation (IAI) on the intensity of the
      fetal inflammatory response and the association between the presence of the fetal
      inflammatory response syndrome (FIRS) and short-term neonatal morbidity in the
      preterm prelabor rupture of membranes (PPROM) between the gestational ages of 34
      and 37 weeks.MethodsOne hundred and fifty-nine women were included in the study.
      The umbilical cord blood interleukin (IL)-6 concentrations were determined using
      enzyme-linked immunosorbent assay kits. FIRS was defined based on the umbilical
      cord blood IL-6 concentration and the presence of funisitis and/or chorionic
      plate vasculitis.ResultsWomen with both MIAC and IAI had the highest median
      umbilical cord blood IL-6 concentrations and highest rates of FIRS. Women with
      FIRS had the higher rates of early-onset sepsis and intraventricular hemorrhage
      grades I and II when FIRS was characterized based on the umbilical cord blood IL
      6 concentrations and the histopathological findings.ConclusionThe presence of
      both MIAC and IAI was associated with a higher fetal inflammatory response and a
      higher rate of FIRS. Different aspects of short-term neonatal morbidity were
      related to FIRS when defined by umbilical cord blood IL-6 concentrations and the
      histopathology of the placenta.

PMID- 29186108
TI  - IL-15 supports the generation of protective lung-resident memory CD4 T cells.
AB  - Tissue-resident memory T cells (TRM) provide optimal defense at the sites of
      infection, but signals regulating their development are unclear, especially for
      CD4 T cells. Here we identify two distinct pathways that lead to the generation
      of CD4 TRM in the lungs following influenza infection. The TRM are
      transcriptionally distinct from conventional memory CD4 T cells and share a gene
      signature with CD8 TRM. The CD4 TRM are superior cytokine producers compared with
      conventional memory cells, can protect otherwise naive mice against a lethal
      influenza challenge, and display functional specialization by inducing enhanced
      inflammatory responses from dendritic cells compared with conventional memory
      cells. Finally, we demonstrate than an interleukin (IL)-2-dependent and a novel
      IL-2-independent but IL-15-dependent pathway support the generation of cohorts of
      lung TRM.

PMID- 29186107
TI  - Mucocutaneous IL-17 immunity in mice and humans: host defense vs. excessive
      inflammation.
AB  - Interleukin (IL)-17A is a pro-inflammatory cytokine in mice and humans. It is
      recognized as a key factor for the protection of mice against various pathogens,
      but it also underlies pathogenic inflammatory responses in numerous mouse models.
      The inborn errors of IL-17A- and IL-17F-mediated immunity identified in humans in
      the last decade have revealed that IL-17A and IL-17F are key players in
      mucocutaneous immunity to Candida albicans, and, to a lesser extent,
      Staphylococcus aureus. By contrast, there is currently no genetic evidence for a
      causal link between excess of IL-17 and autoimmunity, autoinflammation, or
      allergy in humans. We discuss here the physiological and pathological roles of
      mouse and human IL-17A and IL-17F in host defense and excessive inflammation. We
      highlight recent advances in our understanding of the consequences of deficient
      or excessive IL-17 immunity at various mucocutaneous sites, including the oral
      cavity, skin, intestine, lungs, and vagina.

PMID- 29186109
TI  - Absence of specific alternatively spliced exon of CD44 in macrophages prevents
      colitis.
AB  - CD44 is a transmembrane molecule appearing in numerous isoforms generated by
      insertions of alternatively spliced variant exons (CD44v) and having various
      binding partners. CD44v7 on T cells was proposed to promote colitis by preventing
      T-cell apoptosis. Here we demonstrate that Cd44v7-deficient T cells - like Cd44
      wild-type (Cd44WT) T cells - provoked disease in two different colitis models:
      the model induced by CD4+CD45RBhigh T-cell transfer into Rag2-deficient mice and
      a new model based on ovalbumin (OVA)-specific T-cell transfer into Rag
      sufficient, OVA-challenged mice. In contrast, CD44v7 absence on macrophages in
      recipient mice prevented colitis. Prevention was associated with the
      downregulation of signal transducer and activator of transcription 3 (STAT3)
      activating and Foxp3-counteracting interleukin-6 (IL-6), lower numbers of phospho
      STAT3-containing lymphocytes, and higher Foxp3+ T-cell counts in the colon.
      Consequently, the protected colons showed lower IL-12, IL-1beta expression, and
      decreased interferon-gamma levels. Importantly, stimulation of T cells by Cd44v7
      deficient macrophages induced upregulation of Foxp3 in vitro, while cotransfer of
      Cd44WT macrophages into Cd44v7-deficient mice reduced Foxp3+ T-cell counts and
      caused colitis. Accordingly, the CD44v7 ligand osteopontin, whose levels were
      elevated in Crohn's disease, specifically induced IL-6 in human monocytes, a
      cytokine also increased in these patients. We suggest macrophage-specific
      targeting of the CD44v7 pathway as a novel therapeutic option for Crohn's
      disease.

PMID- 29186110
TI  - Direct detection of a break in the teraelectronvolt cosmic-ray spectrum of
      electrons and positrons.
AB  - High-energy cosmic-ray electrons and positrons (CREs), which lose energy quickly
      during their propagation, provide a probe of Galactic high-energy processes and
      may enable the observation of phenomena such as dark-matter particle annihilation
      or decay. The CRE spectrum has been measured directly up to approximately 2
      teraelectronvolts in previous balloon- or space-borne experiments, and indirectly
      up to approximately 5 teraelectronvolts using ground-based Cherenkov gamma-ray
      telescope arrays. Evidence for a spectral break in the teraelectronvolt energy
      range has been provided by indirect measurements, although the results were
      qualified by sizeable systematic uncertainties. Here we report a direct
      measurement of CREs in the energy range 25 gigaelectronvolts to 4.6
      teraelectronvolts by the Dark Matter Particle Explorer (DAMPE) with
      unprecedentedly high energy resolution and low background. The largest part of
      the spectrum can be well fitted by a 'smoothly broken power-law' model rather
      than a single power-law model. The direct detection of a spectral break at about
      0.9 teraelectronvolts confirms the evidence found by previous indirect
      measurements, clarifies the behaviour of the CRE spectrum at energies above 1
      teraelectronvolt and sheds light on the physical origin of the sub
      teraelectronvolt CREs.

PMID- 29186112
TI  - RNA polymerase III limits longevity downstream of TORC1.
AB  - Three distinct RNA polymerases transcribe different classes of genes in the
      eukaryotic nucleus. RNA polymerase (Pol) III is the essential, evolutionarily
      conserved enzyme that generates short, non-coding RNAs, including tRNAs and 5S
      rRNA. The historical focus on transcription of protein-coding genes has left the
      roles of Pol III in organismal physiology relatively unexplored. Target of
      rapamycin kinase complex 1 (TORC1) regulates Pol III activity, and is also an
      important determinant of longevity. This raises the possibility that Pol III is
      involved in ageing. Here we show that Pol III limits lifespan downstream of
      TORC1. We find that a reduction in Pol III extends chronological lifespan in
      yeast and organismal lifespan in worms and flies. Inhibiting the activity of Pol
      III in the gut of adult worms or flies is sufficient to extend lifespan; in
      flies, longevity can be achieved by Pol III inhibition specifically in intestinal
      stem cells. The longevity phenotype is associated with amelioration of age
      related gut pathology and functional decline, dampened protein synthesis and
      increased tolerance of proteostatic stress. Pol III acts on lifespan downstream
      of TORC1, and limiting Pol III activity in the adult gut achieves the full
      longevity benefit of systemic TORC1 inhibition. Hence, Pol III is a pivotal
      mediator of this key nutrient-signalling network for longevity; the growth
      promoting anabolic activity of Pol III mediates the acceleration of ageing by
      TORC1. The evolutionary conservation of Pol III affirms its potential as a
      therapeutic target.

PMID- 29186114
TI  - Corrigendum: Groundwater depletion embedded in international food trade.
AB  - This corrects the article DOI: 10.1038/nature21403.

PMID- 29186111
TI  - Genetic diversity of the African malaria vector Anopheles gambiae.
AB  - The sustainability of malaria control in Africa is threatened by the rise of
      insecticide resistance in Anopheles mosquitoes, which transmit the disease. To
      gain a deeper understanding of how mosquito populations are evolving, here we
      sequenced the genomes of 765 specimens of Anopheles gambiae and Anopheles
      coluzzii sampled from 15 locations across Africa, and identified over 50 million
      single nucleotide polymorphisms within the accessible genome. These data revealed
      complex population structure and patterns of gene flow, with evidence of ancient
      expansions, recent bottlenecks, and local variation in effective population size.
      Strong signals of recent selection were observed in insecticide-resistance genes,
      with several sweeps spreading over large geographical distances and between
      species. The design of new tools for mosquito control using gene-drive systems
      will need to take account of high levels of genetic diversity in natural mosquito
      populations.

PMID- 29186113
TI  - Inactivation of DNA repair triggers neoantigen generation and impairs tumour
      growth.
AB  - Molecular alterations in genes involved in DNA mismatch repair (MMR) promote
      cancer initiation and foster tumour progression. Cancers deficient in MMR
      frequently show favourable prognosis and indolent progression. The functional
      basis of the clinical outcome of patients with tumours that are deficient in MMR
      is not clear. Here we genetically inactivate MutL homologue 1 (MLH1) in
      colorectal, breast and pancreatic mouse cancer cells. The growth of MMR-deficient
      cells was comparable to their proficient counterparts in vitro and on
      transplantation in immunocompromised mice. By contrast, MMR-deficient cancer
      cells grew poorly when transplanted in syngeneic mice. The inactivation of MMR
      increased the mutational burden and led to dynamic mutational profiles, which
      resulted in the persistent renewal of neoantigens in vitro and in vivo, whereas
      MMR-proficient cells exhibited stable mutational load and neoantigen profiles
      over time. Immune surveillance improved when cancer cells, in which MLH1 had been
      inactivated, accumulated neoantigens for several generations. When restricted to
      a clonal population, the dynamic generation of neoantigens driven by MMR further
      increased immune surveillance. Inactivation of MMR, driven by acquired resistance
      to the clinical agent temozolomide, increased mutational load, promoted
      continuous renewal of neoantigens in human colorectal cancers and triggered
      immune surveillance in mouse models. These results suggest that targeting DNA
      repair processes can increase the burden of neoantigens in tumour cells; this has
      the potential to be exploited in therapeutic approaches.

PMID- 29186115
TI  - A transfer-RNA-derived small RNA regulates ribosome biogenesis.
AB  - Transfer-RNA-derived small RNAs (tsRNAs; also called tRNA-derived fragments) are
      an abundant class of small non-coding RNAs whose biological roles are not well
      understood. Here we show that inhibition of a specific tsRNA, LeuCAG3'tsRNA,
      induces apoptosis in rapidly dividing cells in vitro and in a patient-derived
      orthotopic hepatocellular carcinoma model in mice. This tsRNA binds at least two
      ribosomal protein mRNAs (RPS28 and RPS15) to enhance their translation. A
      decrease in translation of RPS28 mRNA blocks pre-18S ribosomal RNA processing,
      resulting in a reduction in the number of 40S ribosomal subunits. These data
      establish a post-transcriptional mechanism that can fine-tune gene expression
      during different physiological states and provide a potential new target for
      treating cancer.

PMID- 29186116
TI  - Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors.
AB  - Malaria is among the most serious infectious diseases affecting humans,
      accounting for approximately half a million deaths each year. Plasmodium
      falciparum causes most life-threatening cases of malaria. Acquired immunity to
      malaria is inefficient, even after repeated exposure to P. falciparum, but the
      immune regulatory mechanisms used by P. falciparum remain largely unknown. Here
      we show that P. falciparum uses immune inhibitory receptors to achieve immune
      evasion. RIFIN proteins are products of a polymorphic multigene family comprising
      approximately 150-200 genes per parasite genome that are expressed on the surface
      of infected erythrocytes. We found that a subset of RIFINs binds to either
      leucocyte immunoglobulin-like receptor B1 (LILRB1) or leucocyte-associated
      immunoglobulin-like receptor 1 (LAIR1). LILRB1-binding RIFINs inhibit activation
      of LILRB1-expressing B cells and natural killer (NK) cells. Furthermore, P.
      falciparum-infected erythrocytes isolated from patients with severe malaria were
      more likely to interact with LILRB1 than erythrocytes from patients with non
      severe malaria, although an extended study with larger sample sizes is required
      to confirm this finding. Our results suggest that P. falciparum has acquired
      multiple RIFINs to evade the host immune system by targeting immune inhibitory
      receptors.

PMID- 29186118
TI  - Corrigendum: A randomized synbiotic trial to prevent sepsis among infants in
      rural India.
AB  - This corrects the article DOI: 10.1038/nature23480.

PMID- 29186117
TI  - Maternal age generates phenotypic variation in Caenorhabditis elegans.
AB  - Genetically identical individuals that grow in the same environment often show
      substantial phenotypic variation within populations of organisms as diverse as
      bacteria, nematodes, rodents and humans. With some exceptions, the causes are
      poorly understood. Here we show that isogenic Caenorhabditis elegans nematodes
      vary in their size at hatching, speed of development, growth rate, starvation
      resistance, fecundity, and also in the rate of development of their germline
      relative to that of somatic tissues. We show that the primary cause of this
      variation is the age of an individual's mother, with the progeny of young mothers
      exhibiting several phenotypic impairments. We identify age-dependent changes in
      the maternal provisioning of the lipoprotein complex vitellogenin to embryos as
      the molecular mechanism that underlies the variation in multiple traits
      throughout the life of an animal. The production of sub-optimal progeny by young
      mothers may reflect a trade-off between the competing fitness traits of a short
      generation time and the survival and fecundity of the progeny.

PMID- 29186121
TI  - Erratum: Quark-level analogue of nuclear fusion with doubly heavy baryons.
AB  - This corrects the article DOI: 10.1038/nature21697.

PMID- 29186119
TI  - Genetically programmed chiral organoborane synthesis.
AB  - Recent advances in enzyme engineering and design have expanded nature's catalytic
      repertoire to functions that are new to biology. However, only a subset of these
      engineered enzymes can function in living systems. Finding enzymatic pathways
      that form chemical bonds that are not found in biology is particularly difficult
      in the cellular environment, as this depends on the discovery not only of new
      enzyme activities, but also of reagents that are both sufficiently reactive for
      the desired transformation and stable in vivo. Here we report the discovery,
      evolution and generalization of a fully genetically encoded platform for
      producing chiral organoboranes in bacteria. Escherichia coli cells harbouring
      wild-type cytochrome c from Rhodothermus marinus (Rma cyt c) were found to form
      carbon-boron bonds in the presence of borane-Lewis base complexes, through
      carbene insertion into boron-hydrogen bonds. Directed evolution of Rma cyt c in
      the bacterial catalyst provided access to 16 novel chiral organoboranes. The
      catalyst is suitable for gram-scale biosynthesis, providing up to 15,300
      turnovers, a turnover frequency of 6,100 h-1, a 99:1 enantiomeric ratio and 100%
      chemoselectivity. The enantiopreference of the biocatalyst could also be tuned to
      provide either enantiomer of the organoborane products. Evolved in the context of
      whole-cell catalysts, the proteins were more active in the whole-cell system than
      in purified forms. This study establishes a DNA-encoded and readily engineered
      bacterial platform for borylation; engineering can be accomplished at a pace that
      rivals the development of chemical synthetic methods, with the ability to achieve
      turnovers that are two orders of magnitude (over 400-fold) greater than those of
      known chiral catalysts for the same class of transformation. This tunable method
      for manipulating boron in cells could expand the scope of boron chemistry in
      living systems.

PMID- 29186120
TI  - Pluripotent state transitions coordinate morphogenesis in mouse and human
      embryos.
AB  - The foundations of mammalian development lie in a cluster of embryonic epiblast
      stem cells. In response to extracellular matrix signalling, these cells undergo
      epithelialization and create an apical surface in contact with a cavity, a
      fundamental event for all subsequent development. Concomitantly, epiblast cells
      transit through distinct pluripotent states, before lineage commitment at
      gastrulation. These pluripotent states have been characterized at the molecular
      level, but their biological importance remains unclear. Here we show that exit
      from an unrestricted naive pluripotent state is required for epiblast
      epithelialization and generation of the pro-amniotic cavity in mouse embryos.
      Embryonic stem cells locked in the naive state are able to initiate polarization
      but fail to undergo lumenogenesis. Mechanistically, exit from naive pluripotency
      activates an Oct4-governed transcriptional program that results in expression of
      glycosylated sialomucin proteins and the vesicle tethering and fusion events of
      lumenogenesis. Similarly, exit of epiblasts from naive pluripotency in cultured
      human post-implantation embryos triggers amniotic cavity formation and
      developmental progression. Our results add tissue-level architecture as a new
      criterion for the characterization of different pluripotent states, and show the
      relevance of transitions between these states during development of the mammalian
      embryo.

PMID- 29186122
TI  - Corrigendum: RNA m6A methylation regulates the ultraviolet-induced DNA damage
      response.
AB  - This corrects the article DOI: 10.1038/nature21671.

PMID- 29186123
TI  - Corrigendum: Mega-evolutionary dynamics of the adaptive radiation of birds.
AB  - This corrects the article DOI: 10.1038/nature21074.

PMID- 29186124
TI  - Reconciling taxon senescence with the Red Queen's hypothesis.
AB  - In the fossil record, taxa exhibit a regular pattern of waxing and waning of
      occupancy, range or diversity between their origin and extinction. This pattern
      appears to contradict the law of constant extinction, which states that the
      probability of extinction in a given taxon is independent of that taxon's age. It
      is nevertheless well established for species, genera and higher taxa of
      terrestrial mammals, marine invertebrates, marine microorganisms, and recent
      Hawaiian clades of animals and plants. Here we show that the apparent
      contradiction between a stochastically constant extinction rate and the seemingly
      deterministic waxing and waning pattern of taxa disappears when we consider their
      peak of expansion rather than their final extinction. To a first approximation,
      we find that biotic drivers of evolution pertain mainly to the peak of taxon
      expansion, whereas abiotic drivers mainly apply to taxon extinction. The Red
      Queen's hypothesis, which emphasizes biotic interactions, was originally proposed
      as an explanation of the law of constant extinction. Much effort has since been
      devoted to determining how this hypothesis, emphasizing competition for
      resources, relates to the effects of environmental change. One proposed
      resolution is that biotic and abiotic processes operate at different scales. By
      focusing attention on taxon expansion rather than survival, we resolve an
      apparent contradiction between the seemingly deterministic waxing and waning
      patterns over time and the randomness of extinction that the Red Queen's
      hypothesis implies.

PMID- 29186126
TI  - Erratum: PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis.
AB  - This corrects the article DOI: 10.1038/nature24649.

PMID- 29186127
TI  - Mismatch repair prefers exons.
AB  - A new analysis of cancer genomes identifies a decrease in the mutation burden of
      exons, but not introns, as compared to expectation. This difference can be
      explained by preferential recruitment of the DNA mismatch repair machinery to a
      protein modification that marks exons.

PMID- 29186128
TI  - Evolutionary insights from wild vervet genomes.
AB  - A new study reports genome-wide variation in 163 vervet monkeys from across their
      taxonomic and geographic ranges. The analysis suggests a complex history of
      admixture and identifies signals of repeated evolutionary selection, some of
      which may be linked to response to simian immunodeficiency virus.

PMID- 29186129
TI  - The hammer of reason.

PMID- 29186125
TI  - Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation
      control.
AB  - N6-methyladenosine (m6A) is an abundant internal RNA modification in both coding
      and non-coding RNAs that is catalysed by the METTL3-METTL14 methyltransferase
      complex. However, the specific role of these enzymes in cancer is still largely
      unknown. Here we define a pathway that is specific for METTL3 and is implicated
      in the maintenance of a leukaemic state. We identify METTL3 as an essential gene
      for growth of acute myeloid leukaemia cells in two distinct genetic screens.
      Downregulation of METTL3 results in cell cycle arrest, differentiation of
      leukaemic cells and failure to establish leukaemia in immunodeficient mice. We
      show that METTL3, independently of METTL14, associates with chromatin and
      localizes to the transcriptional start sites of active genes. The vast majority
      of these genes have the CAATT-box binding protein CEBPZ present at the
      transcriptional start site, and this is required for recruitment of METTL3 to
      chromatin. Promoter-bound METTL3 induces m6A modification within the coding
      region of the associated mRNA transcript, and enhances its translation by
      relieving ribosome stalling. We show that genes regulated by METTL3 in this way
      are necessary for acute myeloid leukaemia. Together, these data define METTL3 as
      a regulator of a chromatin-based pathway that is necessary for maintenance of the
      leukaemic state and identify this enzyme as a potential therapeutic target for
      acute myeloid leukaemia.

PMID- 29186130
TI  - Correcting CRISPR for copy number.
AB  - The CRISPR-Cas9 system enables global screens of gene function with high
      sensitivity and specificity, but off-target effects have been reported for CRISPR
      guide RNAs targeting genes that are amplified at high copy number. A new study
      describes a computational approach to correct for this copy number effect,
      increasing the specificity of CRIPSR screens to identify essential genes.

PMID- 29186132
TI  - Dynamical compensation and structural identifiability of biological models:
      Analysis, implications, and reconciliation.
AB  - The concept of dynamical compensation has been recently introduced to describe
      the ability of a biological system to keep its output dynamics unchanged in the
      face of varying parameters. However, the original definition of dynamical
      compensation amounts to lack of structural identifiability. This is relevant if
      model parameters need to be estimated, as is often the case in biological
      modelling. Care should we taken when using an unidentifiable model to extract
      biological insight: the estimated values of structurally unidentifiable
      parameters are meaningless, and model predictions about unmeasured state
      variables can be wrong. Taking this into account, we explore alternative
      definitions of dynamical compensation that do not necessarily imply structural
      unidentifiability. Accordingly, we show different ways in which a model can be
      made identifiable while exhibiting dynamical compensation. Our analyses enable
      the use of the new concept of dynamical compensation in the context of parameter
      identification, and reconcile it with the desirable property of structural
      identifiability.

PMID- 29186131
TI  - Low-dose proton radiation effects in a transgenic mouse model of Alzheimer's
      disease - Implications for space travel.
AB  - Space radiation represents a significant health risk for astronauts. Ground-based
      animal studies indicate that space radiation affects neuronal functions such as
      excitability, synaptic transmission, and plasticity, and it may accelerate the
      onset of Alzheimer's disease (AD). Although protons represent the main
      constituent in the space radiation spectrum, their effects on AD-related
      pathology have not been tested. We irradiated 3 month-old APP/PSEN1 transgenic
      (TG) and wild type (WT) mice with protons (150 MeV; 0.1-1.0 Gy; whole body) and
      evaluated functional and biochemical hallmarks of AD. We performed behavioral
      tests in the water maze (WM) before irradiation and in the WM and Barnes maze at
      3 and 6 months post-irradiation to evaluate spatial learning and memory. We also
      performed electrophysiological recordings in vitro in hippocampal slices prepared
      6 and 9 months post-irradiation to evaluate excitatory synaptic transmission and
      plasticity. Next, we evaluated amyloid beta (Abeta) deposition in the
      contralateral hippocampus and adjacent cortex using immunohistochemistry. In
      cortical homogenates, we analyzed the levels of the presynaptic marker
      synaptophysin by Western blotting and measured pro-inflammatory cytokine levels
      (TNFalpha, IL-1beta, IL-6, CXCL10 and CCL2) by bead-based multiplex assay. TG
      mice performed significantly worse than WT mice in the WM. Irradiation of TG mice
      did not affect their behavioral performance, but reduced the amplitudes of
      population spikes and inhibited paired-pulse facilitation in CA1 neurons. These
      electrophysiological alterations in the TG mice were qualitatively different from
      those observed in WT mice, in which irradiation increased excitability and
      synaptic efficacy. Irradiation increased Abeta deposition in the cortex of TG
      mice without affecting cytokine levels and increased synaptophysin expression in
      WT mice (but not in the TG mice). Although irradiation with protons increased
      Abeta deposition, the complex functional and biochemical results indicate that
      irradiation effects are not synergistic to AD pathology.

PMID- 29186133
TI  - Mutational analysis of ITPR1 in a Taiwanese cohort with cerebellar ataxias.
AB  - BACKGROUND: The inositol 1,4,5-triphosphate (IP3) receptor type 1 gene (ITPR1)
      encodes the IP3 receptor type 1 (IP3R1), which modulates intracellular calcium
      homeostasis and signaling. Mutations in ITPR1 have been implicated in inherited
      cerebellar ataxias. The aim of this study was to investigate the role of ITPR1
      mutations, including both large segmental deletion and single nucleotide
      mutations, in a Han Chinese cohort with inherited cerebellar ataxias in Taiwan.
      METHODOLOGY AND PRINCIPAL FINDINGS: Ninety-three unrelated individuals with
      molecularly unassigned spinocerebellar ataxia selected from 585 pedigrees with
      autosomal dominant cerebellar ataxias, were recruited into the study with
      elaborate clinical evaluations. The quantitative PCR technique was used to survey
      large segmental deletion of ITPR1 and a targeted sequencing approach was applied
      to sequence all of the 61 exons and the flanking regions of ITPR1. A novel ITPR1
      mutation, c.7721T>C (p.V2574A), was identified in a family with dominantly
      inherited cerebellar ataxia. The proband has an adult-onset non-progressive pure
      cerebellar ataxia and her daughter is afflicted with a childhood onset cerebellar
      ataxia with intellectual sub-normalities. CONCLUSION: ITPR1 mutation is an
      uncommon cause of inherited cerebellar ataxia, accounting for 0.2% (1/585) of
      patients with dominantly inherited cerebellar ataxias in Taiwan. This study
      broadens the mutational spectrum of ITPR1 and also emphasizes the importance of
      considering ITPR1 mutations as a potential cause of inherited cerebellar ataxias.

PMID- 29186134
TI  - An accurate and adaptable photogrammetric approach for estimating the mass and
      body condition of pinnipeds using an unmanned aerial system.
AB  - Measurements of body size and mass are fundamental to pinniped population
      management and research. Manual measurements tend to be accurate but are invasive
      and logistically challenging to obtain. Ground-based photogrammetric techniques
      are less invasive, but inherent limitations make them impractical for many field
      applications. The recent proliferation of unmanned aerial systems (UAS) in
      wildlife monitoring has provided a promising new platform for the photogrammetry
      of free-ranging pinnipeds. Leopard seals (Hydrurga leptonyx) are an apex predator
      in coastal Antarctica whose body condition could be a valuable indicator of
      ecosystem health. We aerially surveyed leopard seals of known body size and mass
      to test the precision and accuracy of photogrammetry from a small UAS. Flights
      were conducted in January and February of 2013 and 2014 and 50 photogrammetric
      samples were obtained from 15 unrestrained seals. UAS-derived measurements of
      standard length were accurate to within 2.01 +/- 1.06%, and paired comparisons
      with ground measurements were statistically indistinguishable. An allometric
      linear mixed effects model predicted leopard seal mass within 19.40 kg (4.4%
      error for a 440 kg seal). Photogrammetric measurements from a single, vertical
      image obtained using UAS provide a noninvasive approach for estimating the mass
      and body condition of pinnipeds that may be widely applicable.

PMID- 29186136
TI  - Development of a shear force measurement dummy for seat comfort.
AB  - Seat comfort is one of the main factors that consumers consider when purchasing a
      car. In this study, we develop a dummy with a shear-force sensor to evaluate seat
      comfort. The sensor has dimensions of 25 mm * 25 mm * 26 mm and is made of S45C.
      Electroless nickel plating is employed to coat its surface in order to prevent
      corrosion and oxidation. The proposed sensor is validated using a qualified load
      cell and shows high accuracy and precision (measurement range: -30-30 N;
      sensitivity: 0.1 N; linear relationship: R = 0.999; transverse sensitivity: <1%).
      The dummy is manufactured in compliance with the SAE standards (SAE J826) and
      incorporates shear sensors into its design. We measure the shear force under four
      driving conditions and at five different speeds using a sedan; results showed
      that the shear force increases with speed under all driving conditions. In the
      case of acceleration and deceleration, shear force significantly changes in the
      lower body of the dummy. During right and left turns, it significantly changes in
      the upper body of the dummy.

PMID- 29186135
TI  - Regulation of actions and habits by ventral hippocampal trkB and adolescent
      corticosteroid exposure.
AB  - In humans and rodents, stress promotes habit-based behaviors that can interfere
      with action-outcome decision-making. Further, developmental stressor exposure
      confers long-term habit biases across rodent-primate species. Despite these
      homologies, mechanisms remain unclear. We first report that exposure to the
      primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates
      multiple neurobehavioral consequences of stressor exposure, including long
      lasting biases towards habit-based responding in a food-reinforced operant
      conditioning task. In both adolescents and adults, CORT also caused a shift in
      the balance between full-length tyrosine kinase receptor B (trkB) and a truncated
      form of this neurotrophin receptor, favoring the inactive form throughout
      multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB
      substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral
      hippocampus was also diminished, a long-term effect that persisted for at least
      12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during
      adolescence at doses that stimulated ERK42/44 corrected long-lasting
      corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated
      overexpression of truncated trkB in the ventral hippocampus reduced local
      ERK42/44 phosphorylation and was sufficient to induce habit-based and depression
      like behaviors. Together, our findings indicate that ventral hippocampal trkB is
      essential to goal-directed action selection, countering habit-based behavior
      otherwise facilitated by developmental stress hormone exposure. They also reveal
      an early-life sensitive period during which trkB-ERK42/44 tone determines long
      term behavioral outcomes.

PMID- 29186137
TI  - Evaluation of the implementation fidelity of the seasonal malaria chemoprevention
      intervention in Kaya health district, Burkina Faso.
AB  - BACKGROUND: Burkina Faso implemented the seasonal malaria chemoprevention (SMC)
      in 2014 in seven pilot health districts, following the new recommendation by the
      WHO in 2012 for the prevention of the disease in children under five years old,
      for areas of highly seasonal malaria transmission.The objective of this study was
      to assess the implementation fidelity of the seasonal malaria chemoprevention
      strategy in one of the districts, Kaya Health District. METHODOLOGY: We conducted
      a case study, with a quantitative and qualitative mixed methods. Data were
      collected after two campaigns of implementation of the intervention, in 2014 and
      2015, through a review of specific documents of SMC intervention, and individual
      interview with key informants (n = 21) involved at various levels in the
      implementation of the strategy and a household survey with the parents (n = 284)
      of eligible children for the SMC strategy in 2015 in the Kaya health district.
      The analysis framework focused on the fidelity of the intervention's content, its
      coverage, and its schedule, as well as the potential moderating factors, using
      the model proposed by Hasson, originally from Carroll. RESULTS: All components of
      the intervention were implemented. Villages and sectors were covered at 100%. In
      terms of intervention doses received, less than one-third of eligible children
      (32.3%) received the recommended four doses in 2015. Implementation of the
      strategy faced some difficulties due to insufficient training of community
      distributors, inadequate supply of inputs and insufficient financial resources
      for remuneration, advocacy and supervision, but also because of the contextual
      constraints due to the rainy season. Moreover, an interaction between the
      different moderating factors, influencing the degree of implementation of the
      strategy was noted. CONCLUSION: Taking into account the moderating factors of the
      implementation is necessary for achieving the highest possible degree of
      implementation fidelity and then, reach the expected beneficial effects.

PMID- 29186138
TI  - Biodiversity conservation values of fragmented communally reserved forests,
      managed by indigenous people, in a human-modified landscape in Borneo.
AB  - This study explored the conservation values of communally reserved forests
      (CRFs), which local indigenous communities deliberately preserve within their
      area of shifting cultivation. In the current landscape of rural Borneo, CRFs are
      the only option for conservation because other forested areas have already been
      logged or transformed into plantations. By analyzing their alpha and beta
      diversity, we investigated how these forests can contribute to restore regional
      biodiversity. Although CRFs were fragmented and some had been disturbed in the
      past, their tree species diversity was high and equivalent to that of primary
      forests. The species composition of intact forests and forests disturbed in the
      past did not differ clearly, which indicates that past logging was not intensive.
      All CRFs contained unique and endangered species, which are on the IUCN Red List,
      Sarawak protected plants, or both. On the other hand, the forest size structure
      differed between disturbed and intact CRFs, with the disturbed CRFs consisting of
      relatively smaller trees. Although the beta diversity among CRFs was also high,
      we found a high contribution of species replacement (turnover), but not of
      richness difference, in the total beta diversity. This suggests that all CRFs
      have a conservation value for restoring the overall regional biodiversity.
      Therefore, for maintaining the regional species diversity and endangered species,
      it would be suitable to design a conservation target into all CRFs.

PMID- 29186140
TI  - Phylogeography of the termite Macrotermes gilvus and insight into ancient
      dispersal corridors in Pleistocene Southeast Asia.
AB  - Dispersal of soil-dwelling organisms via the repeatedly exposed Sunda shelf
      through much of the Pleistocene in Southeast Asia has not been studied
      extensively, especially for invertebrates. Here we investigated the
      phylogeography of an endemic termite species, Macrotermes gilvus (Hagen), to
      elucidate the spatiotemporal dynamics of dispersal routes of terrestrial fauna in
      Pleistocene Southeast Asia. We sampled 213 termite colonies from 66 localities
      throughout the region. Independently inherited microsatellites and mtDNA markers
      were used to infer the phylogeographic framework of M. gilvus. Discrete
      phylogeographic analysis and molecular dating based on fossil calibration were
      used to infer the dynamics of M. gilvus dispersal in time and space across
      Southeast Asia. We found that the termite dispersal events were consistently
      dated within the Pleistocene time frame. The dispersal pattern was
      multidirectional, radiating eastwards and southwards out of Indochina, which was
      identified as the origin for dispersal events. We found no direct dispersal
      events between Sumatra and Borneo despite the presence of a terrestrial
      connection between them during the Pleistocene. Instead, central Java served as
      an important link allowing termite colonies to be established in Borneo and
      Sumatra. Our findings support the hypothesis of a north-south dispersal corridor
      in Southeast Asia and suggest the presence of alternative dispersal routes across
      Sundaland during the Pleistocene. For the first time, we also propose that a west
      east dispersal through over-water rafting likely occurred across the Pleistocene
      South China Sea. We found at least two independent entry routes for terrestrial
      species to infiltrate Sumatra and Borneo at different times.

PMID- 29186139
TI  - Identification and characterization of novel cecropins from the Oxysternon
      conspicillatum neotropic dung beetle.
AB  - Dung beetles are exposed to a complex microbiological ecosystem during their life
      cycle. Characterization of novel host-defense peptides (HDP) is essential to
      understanding the host innate immune response in insects. It constitutes a
      promising alternative to look for new therapeutic agents against pathogenic
      microbes. We identified four new HDP, Oxysterlins 1, 2, 3, and 4 from the
      transcriptome of the Oxysternon conspicillatum dung beetle. These HDP display a
      highly conserved signal peptide and a mature peptide, characterized by an overall
      positive charge (cationic) (pI: 10.23-11.49), a hydrophobic ratio (PhiH: 35-41),
      and amphipathicity. Oxysterlins 1, 2, and 3 have a linear alpha-helix structure,
      whilst Oxysterlin 4 has a mixture of both alpha-helix and beta-sheet structures
      without disulfide bonds through bioinformatics prediction and circular dichroism.
      Oxysterlins are part of the cecropin family group in an exclusive clade related
      to beetle cecropins. They have predominant antimicrobial activity against Gram
      negative bacteria, including multidrug resistant strains (3.12-50 MUg/mL)
      measured by plate microdilution. Their kinetics, in a time-killing curve showed
      concentration-dependent bactericidal activity. Furthermore, these HDP have low
      toxicity against human erythrocytes (62.5-500 MUg/mL) and Vero cells (250-500
      MUg/mL). This article describes new HDP of the cecropin family from the
      Oxysternon conspicillatum dung beetle, with antimicrobial activity against
      multidrug resistant bacteria and low toxicity.

PMID- 29186141
TI  - Understanding disciplinary vocabularies using a full-text enabled domain
      independent term extraction approach.
AB  - Publication metadata help deliver rich analyses of scholarly communication.
      However, research concepts and ideas are more effectively expressed through
      unstructured fields such as full texts. Thus, the goals of this paper are to
      employ a full-text enabled method to extract terms relevant to disciplinary
      vocabularies, and through them, to understand the relationships between
      disciplines. This paper uses an efficient, domain-independent term extraction
      method to extract disciplinary vocabularies from a large multidisciplinary corpus
      of PLoS ONE publications. It finds a power-law pattern in the frequency
      distributions of terms present in each discipline, indicating a semantic richness
      potentially sufficient for further study and advanced analysis. The salient
      relationships amongst these vocabularies become apparent in application of a
      principal component analysis. For example, Mathematics and Computer and
      Information Sciences were found to have similar vocabulary use patterns along
      with Engineering and Physics; while Chemistry and the Social Sciences were found
      to exhibit contrasting vocabulary use patterns along with the Earth Sciences and
      Chemistry. These results have implications to studies of scholarly communication
      as scholars attempt to identify the epistemological cultures of disciplines, and
      as a full text-based methodology could lead to machine learning applications in
      the automated classification of scholarly work according to disciplinary
      vocabularies.

PMID- 29186142
TI  - Breastfeeding and maternal cardiovascular risk factors and outcomes: A systematic
      review.
AB  - BACKGROUND: There is growing evidence that breastfeeding has short- and long-term
      cardiovascular health benefits for mothers. The objectives of this systematic
      review were to examine the association between breastfeeding and maternal
      cardiovascular risk factors and outcomes that have not previously been
      synthesized systematically, including metabolic syndrome, hypertension and
      cardiovascular disease. METHODS AND FINDINGS: This systematic review meets PRISMA
      guidelines. The MEDLINE, EMBASE and CINAHL databases were systematically searched
      for relevant publications of any study design from the earliest publication date
      to March 2016. The reference lists from selected articles were reviewed, and
      forward and backward referencing were conducted. The methodological quality of
      reviewed articles was appraised using validated checklists. Twenty-one studies
      meeting the inclusion criteria examined the association between self-reported
      breastfeeding and one or more of the following outcomes: metabolic
      syndrome/metabolic risk factors (n = 10), inflammatory markers/adipokines (n =
      2), hypertension (n = 7), subclinical cardiovascular disease (n = 2),
      prevalence/incidence of cardiovascular disease (n = 3) and cardiovascular disease
      mortality (n = 2). Overall, 19 studies (10 cross-sectional/retrospective, 9
      prospective) reported significant protective effects of breastfeeding, nine
      studies (3 cross-sectional/retrospective, 5 prospective, 1 cluster randomized
      controlled trial) reported non-significant findings and none reported detrimental
      effects of breastfeeding. In most studies reporting significant associations,
      breastfeeding remained associated with both short- and long-term maternal
      cardiovascular health risk factors/outcomes, even after covariate adjustment.
      Findings from several studies suggested that the effects of breastfeeding may
      diminish with age and a dose-response association between breastfeeding and
      several metabolic risk factors. However, further longitudinal studies, including
      studies that measure exclusive breastfeeding, are needed to confirm these
      findings. CONCLUSIONS: The evidence from this review suggests that breastfeeding
      is associated with cardiovascular health benefits. However, results should be
      interpreted with caution as the evidence gathered for each individual outcome was
      limited by the small number of observational studies. Additional prospective
      studies are needed. PROSPERO REGISTRATION NUMBER: CRD42016047766.

PMID- 29186143
TI  - Comparative growth rates of cultured marine dinoflagellates in the genus
      Symbiodinium and the effects of temperature and light.
AB  - Many dinoflagellate microalgae of the genus Symbiodinium form successful
      symbioses with a large group of metazoans and selected protists. Yet knowledge of
      growth kinetics of these endosymbionts and their ecological and evolutionary
      implications is limited. We used a Bayesian biphasic generalized logistic model
      to estimate key parameters of the growth of five strains of cultured
      Symbiodinium, S. microadriaticum (cp-type A194; strain 04-503), S.
      microadriaticum (cp-type A194; strain CassKB8), S. minutum (cp-type B184; strain
      Mf 1.05b.01.SCI.01), S. psygmophilum (cp-type B224; strain Mf 11.05b.01) and S.
      trenchii (cp-type D206; strain Mf 2.2b), grown in four different combinations of
      temperature and light. Growth kinetics varied among Symbiodinium strains and
      across treatments. Biphasic growth was especially evident for S. minutum and S.
      psygmophilum across all treatments. Monophasic growth was more common when final
      asymptotic densities were relatively low (~ 200 million cells ml-1). All species
      tended to grow faster and / or reached a higher asymptote at 26 degrees C than at
      18 degrees C. The fastest growth was exhibited by S. minutum, with an approximate
      four-fold increase in estimated cell density after 60 days. The strongest effect
      of light was seen in S. trenchii, in which increasing light levels resulted in a
      decrease in initial growth rate, and an increase in asymptotic density, time when
      growth rate was at its maximum, final growth rate, and maximum growth rate.
      Results suggest that Symbiodinium species have different photokinetic and thermal
      optima, which may affect their growth-related nutritional physiology and allow
      them to modify their response to environmental changes.

PMID- 29186144
TI  - Time trends in antibiotic consumption in the elderly: Ten-year follow-up of the
      Spanish National Health Survey and the European Health Interview Survey for Spain
      (2003-2014).
AB  - BACKGROUND: The purposes of this study were: firstly, to estimate time trends in
      the prevalence of prescription antibiotic consumption between 2003 and 2014;
      secondly, to identify the factors associated with the probability of consuming
      antibiotics during this period in elderly persons in Spain. METHODS: We analyzed
      data collected from the Spanish National Health Survey in 2003 (n = 21,650), 2006
      (n = 29,478), and 2012 (n = 20,007) and from the European Health Interview Survey
      for Spain in 2009 (n = 22,188) and 2014 (n = 22,842). Antibiotic consumption was
      the dependent variable. We also analyzed sociodemographic features, self
      perceived health status, lifestyle habits, comorbid diseases, and disabilities
      using logistic regression models. RESULTS: The prevalence of antibiotic
      consumption increased from 2003 to 2014 in both sexes. The variables that
      predicted antibiotic consumption (men; women) were secondary education (OR 1.38;
      OR 1.31), visits to a general practitioner (OR 2.05; OR 2.15), hospitalization
      (OR 1.91; OR 1.83), therapy with > 4 non-antibiotic drugs (OR 3.36; OR 5.84),
      instrumental activities of daily living (OR 1.50; OR 1.24), and activities of
      daily living (OR 1.39; OR 1.35). In contrast, age > 85 years was associated with
      low antibiotic consumption in both men (OR 0.81) and women (OR 0.88).
      CONCLUSIONS: The prevalence of antibiotic prescription has increased in Spain in
      the last decade. Our study identified several factors that appear to affect
      antibiotic consumption in elderly persons, with potential implications for
      healthcare providers.

PMID- 29186145
TI  - Respective impact of implementation of prevention strategies, colonization with
      multiresistant bacteria and antimicrobial use on the risk of early- and late
      onset VAP: An analysis of the OUTCOMEREA network.
AB  - RATIONALE: The impact of prevention strategies and risk factors for early-onset
      (EOP) versus late-onset (LOP) ventilator-associated pneumonia (VAP) are still
      debated. OBJECTIVES: To evaluate, in a multicenter cohort, the risk factors for
      EOP and LOP, as the evolution of prevention strategies. METHODS: 7,784 patients
      with mechanical ventilation (MV) for at least 48 hours were selected into the
      multicenter prospective OUTCOMEREA database (1997-2016). VAP occurring between
      the 3rd and 6th day of MV defined EOP, while those occurring after defined LOPs.
      We used a Fine and Gray subdistribution model to take the successful extubation
      into account as a competing event. MEASUREMENTS AND MAIN RESULTS: Overall, 1,234
      included patients developed VAP (EOP: 445 (36%); LOP: 789 (64%)). Male gender was
      a risk factor for both EOP and LOP. Factors specifically associated with EOP were
      admission for respiratory distress, previous colonization with multidrug
      resistant Pseudomonas aeruginosa, chest tube and enteral feeding within the first
      2 days of MV. Antimicrobials administrated within the first 2 days of MV were all
      protective of EOP. ICU admission for COPD exacerbation or pneumonia were early
      risk factors for LOP, while imidazole and vancomycin use within the first 2 days
      of MV were protective factors. Late risk factors (between the 3rd and the 6th day
      of MV) were the intra-hospital transport, PAO2-FIO2<200 mmHg, vasopressor use,
      and known colonization with methicillin-resistant Staphylococcus aureus. Among
      the antimicrobials administered between the 3rd and the 6th day, fluoroquinolones
      were the solely protective one.Contrarily to LOP, the risk of EOP decreased
      across the study time periods, concomitantly with an increase in the compliance
      with bundle of prevention measures. CONCLUSION: VAP risk factors are mostly
      different according to the pneumonia time of onset, which should lead to
      differentiated prevention strategies.

PMID- 29186147
TI  - Testing the Sensory Drive Hypothesis: Geographic variation in echolocation
      frequencies of Geoffroy's horseshoe bat (Rhinolophidae: Rhinolophus clivosus).
AB  - Geographic variation in sensory traits is usually influenced by adaptive
      processes because these traits are involved in crucial life-history aspects
      including orientation, communication, lineage recognition and mate choice.
      Studying this variation can therefore provide insights into lineage
      diversification. According to the Sensory Drive Hypothesis, lineage
      diversification may be driven by adaptation of sensory systems to local
      environments. It predicts that acoustic signals vary in association with local
      climatic conditions so that atmospheric attenuation is minimized and transmission
      of the signals maximized. To test this prediction, we investigated the influence
      of climatic factors (specifically relative humidity and temperature) on
      geographic variation in the resting frequencies of the echolocation pulses of
      Geoffroy's horseshoe bat, Rhinolophus clivosus. If the evolution of phenotypic
      variation in this lineage tracks climate variation, human induced climate change
      may lead to decreases in detection volumes and a reduction in foraging
      efficiency. A complex non-linear interaction between relative humidity and
      temperature affects atmospheric attenuation of sound and principal components
      composed of these correlated variables were, therefore, used in a linear mixed
      effects model to assess their contribution to observed variation in resting
      frequencies. A principal component composed predominantly of mean annual
      temperature (factor loading of -0.8455) significantly explained a proportion of
      the variation in resting frequency across sites (P < 0.05). Specifically, at
      higher relative humidity (around 60%) prevalent across the distribution of R.
      clivosus, increasing temperature had a strong negative effect on resting
      frequency. Climatic factors thus strongly influence acoustic signal divergence in
      this lineage, supporting the prediction of the Sensory Drive Hypothesis. The
      predicted future increase in temperature due to climate change is likely to
      decrease the detection volume in echolocating bats and adversely impact their
      foraging efficiency.

PMID- 29186146
TI  - Auditory and cognitive performance in elderly musicians and nonmusicians.
AB  - Musicians represent a model for examining brain and behavioral plasticity in
      terms of cognitive and auditory profile, but few studies have investigated
      whether elderly musicians have better auditory and cognitive abilities than
      nonmusicians. The aim of the present study was to examine whether being a
      professional musician attenuates the normal age-related changes in hearing and
      cognition. Elderly musicians still active in their profession were compared with
      nonmusicians on auditory performance (absolute threshold, frequency intensity,
      duration and spectral shape discrimination, gap and sinusoidal amplitude
      modulation detection), and on simple (short-term memory) and more complex and
      higher-order (working memory [WM] and visuospatial abilities) cognitive tasks.
      The sample consisted of adults at least 65 years of age. The results showed that
      older musicians had similar absolute thresholds but better supra-threshold
      discrimination abilities than nonmusicians in four of the six auditory tasks
      administered. They also had a better WM performance, and stronger visuospatial
      abilities than nonmusicians. No differences were found between the two groups'
      short-term memory. Frequency discrimination and gap detection for the auditory
      measures, and WM complex span tasks and one of the visuospatial tasks for the
      cognitive ones proved to be very good classifiers of the musicians. These
      findings suggest that life-long music training may be associated with enhanced
      auditory and cognitive performance, including complex cognitive skills, in
      advanced age. However, whether this music training represents a protective factor
      or not needs further investigation.

PMID- 29186148
TI  - A case-control collapsing analysis identifies epilepsy genes implicated in trio
      sequencing studies focused on de novo mutations.
AB  - Trio exome sequencing has been successful in identifying genes with de novo
      mutations (DNMs) causing epileptic encephalopathy (EE) and other
      neurodevelopmental disorders. Here, we evaluate how well a case-control
      collapsing analysis recovers genes causing dominant forms of EE originally
      implicated by DNM analysis. We performed a genome-wide search for an enrichment
      of "qualifying variants" in protein-coding genes in 488 unrelated cases compared
      to 12,151 unrelated controls. These "qualifying variants" were selected to be
      extremely rare variants predicted to functionally impact the protein to enrich
      for likely pathogenic variants. Despite modest sample size, three known EE genes
      (KCNT1, SCN2A, and STXBP1) achieved genome-wide significance (p<2.68*10-6). In
      addition, six of the 10 most significantly associated genes are known EE genes,
      and the majority of the known EE genes (17 out of 25) originally implicated in
      trio sequencing are nominally significant (p<0.05), a proportion significantly
      higher than the expected (Fisher's exact p = 2.33*10-17). Our results indicate
      that a case-control collapsing analysis can identify several of the EE genes
      originally implicated in trio sequencing studies, and clearly show that
      additional genes would be implicated with larger sample sizes. The case-control
      analysis not only makes discovery easier and more economical in early onset
      disorders, particularly when large cohorts are available, but also supports the
      use of this approach to identify genes in diseases that present later in life
      when parents are not readily available.

PMID- 29186149
TI  - The alkalophilic fungus Sodiomyces alkalinus hosts beta- and gammapartitiviruses
      together with a new fusarivirus.
AB  - Mixed infection by three dsRNA viruses, a novel betapartitivirus, a
      gammapartitivirus, and a novel fusarivirus, has been identified in four isolates
      of the obligate alkalophilic fungus Sodiomyces alkalinus. The first, Sodiomyces
      alkalinus partitivirus 1 (SaPV1), is placed within the genus Betapartitivirus and
      is related to Ustilaginoidea virens partitivirus 2. The taxonomic position of the
      second virus is less clear as it shares high (85%) amino acid sequence identity
      but significantly low (77%) nucleotide sequence identity of the capsid protein
      with Colletotrichum truncatum partitivirus 1. The third, the novel Sodiomyces
      alkalinus fusarivirus 1 (SaFV1), is related to Fusarium poae fusarivirus 1. All
      the viruses show efficient vertical transmission through asexual and sexual
      spores. These novel coexisting viruses do not evoke apparent phenotypic
      alteration to their fungal host. This is the first description of a viral
      infection in an alkalophilic fungus.

PMID- 29186150
TI  - In vitro enteroid-derived three-dimensional tissue model of human small
      intestinal epithelium with innate immune responses.
AB  - There is a need for functional in vitro 3D human intestine systems that can
      bridge the gap between conventional cell culture studies and human trials. The
      successful engineering in vitro of human intestinal tissues relies on the use of
      the appropriate cell sources, biomimetic scaffolds, and 3D culture conditions to
      support vital organ functions. We previously established a compartmentalized
      scaffold consisting of a hollow space within a porous bulk matrix, in which a
      functional and physiologically relevant intestinal epithelium system was
      generated using intestinal cell lines. In this study, we adopt the 3D scaffold
      system for the cultivation of stem cell-derived human small intestinal enteriods
      (HIEs) to engineer an in vitro 3D model of a nonstransformed human small
      intestinal epithelium. Characterization of tissue properties revealed a mature
      HIE-derived epithelium displaying four major terminally differentiated epithelial
      cell types (enterocytes, Goblet cells, Paneth cells, enteroendocrine cells), with
      tight junction formation, microvilli polarization, digestive enzyme secretion,
      and low oxygen tension in the lumen. Moreover, the tissue model demonstrates
      significant antibacterial responses to E. coli infection, as evidenced by the
      significant upregulation of genes involved in the innate immune response.
      Importantly, many of these genes are activated in human patients with
      inflammatory bowel disease (IBD), implicating the potential application of the 3D
      stem-cell derived epithelium for the in vitro study of host-microbe-pathogen
      interplay and IBD pathogenesis.

PMID- 29186151
TI  - Difference between ejection times measured at two different peripheral locations
      as a novel marker of vascular stiffness.
AB  - Pulse wave velocity (PWV) has been recommended as an arterial damage assessment
      tool and a surrogate of arterial stiffness. However, the current technology does
      not allow to measure PWV both continuously and in real-time. We reported
      previously that peripherally measured ejection time (ET) overestimates ET
      measured centrally. This difference in ET is associated with the inherent
      vascular properties of the vessel. In the current study we examined ETs derived
      from plethysmography simultaneously at different peripheral locations and
      examined the influence of the underlying arterial properties on ET prolongation
      by changing the subject's position. We calculated the ET difference between two
      peripheral locations (DeltaET) and its corresponding PWV for the same heartbeat.
      The DeltaET increased with a corresponding decrease in PWV. The difference
      between DeltaET in the supine and standing (which we call ET index) was higher in
      young subjects with low mean arterial pressure and low PWV. These results suggest
      that the difference in ET between two peripheral locations in the supine vs
      standing positions represents the underlying vascular properties. We propose
      DeltaET in the supine position as a potential novel real-time continuous and non
      invasive parameter of vascular properties, and the ET index as a potential non
      invasive parameter of vascular reactivity.

PMID- 29186153
TI  - The peer review gap: A longitudinal case study of gendered publishing and
      occupational patterns in a female-rich discipline, Western North America (1974
      2016).
AB  - Researchers have repeatedly demonstrated that women continue to be
      underrepresented in publication output in the sciences. This is true even in
      female-rich fields such as archaeology. Since most gender-related publication
      studies rely on data from peer-reviewed journals, it would be instructive, though
      challenging, to also track publication output in non-refereed and professional or
      industry venues, which tend to be more accessible to those working in extra
      academic settings. This comparison is important in fields such as archaeology in
      which the vast majority (approximately 90%) of practitioners in the USA work for
      private sector cultural resource management firms and federal and state agencies.
      To understand the dynamics of who publishes where, we compiled a new dataset
      tracking over 40 years of peer-reviewed versus non-peer-reviewed publications
      that publish articles on the archaeology of California (an American Indian
      cultural area including southwest Oregon, most of the state of California, and
      Baja Mexico) and the Great Basin culture area (spanning eight western USA
      states). Historic gender differences in the publishing output of authors
      identified as men versus those identified as women were revealed by articles
      published between 1974 and 2016 in two refereed journals, the Journal of
      California Anthropology/ Journal of California and Great Basin Anthropology and
      California Archaeology, and in one un-refereed venue, the Society for California
      Archaeology Proceedings. Although multiple independent measures indicate that
      women are contributing and active members of the discipline, publishing records
      yield more variable results. Specifically, while women have historic and
      increasingly robust levels of participation in the non-peer-reviewed Proceedings,
      they remain vastly underrepresented in the two peer-reviewed journals, which are
      widely regarded as more prestigious and influential. We argue that this "peer
      review gap" is influenced by variation in the costs (largely time investment) and
      benefits of publication for people working in different professional roles (e.g.,
      agency professionals, private/cultural resource management firm personnel, tenure
      track faculty, adjunct faculty, etc.). We also argue that these cost and benefit
      variations may ultimately influence the decisions of people of all genders and
      backgrounds, but, because of the current structure of our discipline-including
      the fact that women and minorities lag in positions where costly peer-reviewed
      publication is a rewarded and supported activity-overwhelmingly affect these
      groups. We recognize that non-refereed publications such as Proceedings provide
      an important means of bridging the peer review gap and give voice to individuals
      from diverse backgrounds and perspectives.

PMID- 29186154
TI  - External validation of a collar-mounted triaxial accelerometer for second-by
      second monitoring of eight behavioural states in dogs.
AB  - Early detection of disease by an animal owner may motivate them to seek early
      veterinary advice. Presentation before a more advanced clinical manifestation is
      evident could lead to more effective treatment and thus benefit the animal's
      health and welfare. Accelerometers are able to detect changes in specific
      activities or behaviours, thus indicating early signs of possible adverse health
      events. The objective of this validation study was to determine whether the
      detection of eight behavioural states: walk, trot, canter/gallop, sleep,
      static/inactive, eat, drink, and headshake, by an accelerometer device was
      sufficiently accurate to be useful in a clinical setting. This fully independent
      external validation estimated the accuracy of a specific triaxial, collar-mounted
      accelerometer on a second-by second basis in 51 healthy dogs of different breeds,
      aged between 6 months and 13 years, weighing >10 kg. The overall diagnostic
      effectiveness was estimated as: % record correctly classified of > 95% in walk,
      trot, canter/gallop, eat, drink and headshake and >90% in sleep and
      static/inactive. The positive predictive values ranged from 93-100%, while the
      negative predictive values ranged from 96-100%, with exception of static/inactive
      (86%).This was probably because dogs were placed in unfamiliar kennels where they
      did not exhibit their typical resting behaviour. The device is worn on a collar,
      making its use feasible for anyone wanting to monitor their dog's behaviour. The
      high accuracy in detecting various kinds of behaviour appears promising in
      assessing canine health and welfare states.

PMID- 29186152
TI  - High-throughput full-length single-cell mRNA-seq of rare cells.
AB  - Single-cell characterization techniques, such as mRNA-seq, have been applied to a
      diverse range of applications in cancer biology, yielding great insight into
      mechanisms leading to therapy resistance and tumor clonality. While single-cell
      techniques can yield a wealth of information, a common bottleneck is the lack of
      throughput, with many current processing methods being limited to the analysis of
      small volumes of single cell suspensions with cell densities on the order of 107
      per mL. In this work, we present a high-throughput full-length mRNA-seq protocol
      incorporating a magnetic sifter and magnetic nanoparticle-antibody conjugates for
      rare cell enrichment, and Smart-seq2 chemistry for sequencing. We evaluate the
      efficiency and quality of this protocol with a simulated circulating tumor cell
      system, whereby non-small-cell lung cancer cell lines (NCI-H1650 and NCI-H1975)
      are spiked into whole blood, before being enriched for single-cell mRNA-seq by
      EpCAM-functionalized magnetic nanoparticles and the magnetic sifter. We obtain
      high efficiency (> 90%) capture and release of these simulated rare cells via the
      magnetic sifter, with reproducible transcriptome data. In addition, while mRNA
      seq data is typically only used for gene expression analysis of transcriptomic
      data, we demonstrate the use of full-length mRNA-seq chemistries like Smart-seq2
      to facilitate variant analysis of expressed genes. This enables the use of mRNA
      seq data for differentiating cells in a heterogeneous population by both their
      phenotypic and variant profile. In a simulated heterogeneous mixture of
      circulating tumor cells in whole blood, we utilize this high-throughput protocol
      to differentiate these heterogeneous cells by both their phenotype (lung cancer
      versus white blood cells), and mutational profile (H1650 versus H1975 cells), in
      a single sequencing run. This high-throughput method can help facilitate single
      cell analysis of rare cell populations, such as circulating tumor or endothelial
      cells, with demonstrably high-quality transcriptomic data.

PMID- 29186155
TI  - Using iterative learning to improve understanding during the informed consent
      process in a South African psychiatric genomics study.
AB  - Obtaining informed consent is a great challenge in global health research. There
      is a need for tools that can screen for and improve potential research
      participants' understanding of the research study at the time of recruitment.
      Limited empirical research has been conducted in low and middle income countries,
      evaluating informed consent processes in genomics research. We sought to
      investigate the quality of informed consent obtained in a South African
      psychiatric genomics study. A Xhosa language version of the University of
      California, San Diego Brief Assessment of Capacity to Consent Questionnaire
      (UBACC) was used to screen for capacity to consent and improve understanding
      through iterative learning in a sample of 528 Xhosa people with schizophrenia and
      528 controls. We address two questions: firstly, whether research participants'
      understanding of the research study improved through iterative learning; and
      secondly, what were predictors for better understanding of the research study at
      the initial screening? During screening 290 (55%) cases and 172 (33%) controls
      scored below the 14.5 cut-off for acceptable understanding of the research study
      elements, however after iterative learning only 38 (7%) cases and 13 (2.5%)
      controls continued to score below this cut-off. Significant variables associated
      with increased understanding of the consent included the psychiatric nurse
      recruiter conducting the consent screening, higher participant level of
      education, and being a control. The UBACC proved an effective tool to improve
      understanding of research study elements during consent, for both cases and
      controls. The tool holds utility for complex studies such as those involving
      genomics, where iterative learning can be used to make significant improvements
      in understanding of research study elements. The UBACC may be particularly
      important in groups with severe mental illness and lower education levels. Study
      recruiters play a significant role in managing the quality of the informed
      consent process.

PMID- 29186156
TI  - A common mechanism by which type 2A von Willebrand disease mutations enhance
      ADAMTS13 proteolysis revealed with a von Willebrand factor A2 domain FRET
      construct.
AB  - Rheological forces in the blood trigger the unfolding of von Willebrand factor
      (VWF) and its A2 domain, exposing the scissile bond for proteolysis by ADAMTS13.
      Under quiescent conditions, the scissile bond is hidden by the folded structure
      due to the stabilisation provided by the structural specialisations of the VWF A2
      domain, a vicinal disulphide bond, a calcium binding site and a N1574-glycan.The
      reduced circulating high MW multimers of VWF in patients with type 2A von
      Willebrand disease (VWD) may be associated with mutations within the VWF A2
      domain and this is attributed to enhanced ADAMTS13 proteolysis. We investigated
      11 VWF A2 domain variants identified in patients with type 2A VWD. In recombinant
      full-length VWF, enhanced ADAMTS13 proteolysis was detected for all of the
      expressed variants in the presence of urea-induced denaturation. A subset of the
      FLVWF variants displayed enhanced proteolysis in the absence of urea. The
      mechanism of enhancement was investigated using a novel VWF A2 domain FRET
      construct. In the absence of induced unfolding, 7/8 of the expressed mutants
      exhibited a disrupted domain fold, causing spatial separation of the N- and C-
      termini. Three of the type 2A mutants were not secreted when studied within the
      VWF A2 domain FRET construct. Urea denaturation revealed for all 8 secreted
      mutants reduced unfolding cooperativity and stability of the VWF A2 domain. As
      folding stability was progressively disrupted, proteolysis by ADAMTS13 increased.
      Due to the range of folding stabilities and wide distribution of VWF A2 domain
      mutations studied, we conclude that these mutations disrupt regulated folding of
      the VWF A2 domain. They enhance unfolding by inducing separation of N- and C
      termini, thereby promoting a more open conformation that reveals its binding
      sites for ADAMTS13 and the scissile bond.

PMID- 29186158
TI  - Determinants and effects of medical students' core self-evaluation tendencies on
      clinical competence and workplace well-being in clerkship.
AB  - Core self-evaluation (CSE) is a personality trait that involves a person's
      evaluation of his or her own worth, competence, and capability. The objective of
      this study was to determine whether medical students' CSEs exert beneficial
      effects on their adaptation to their clerkship in terms of their clinical
      competence and workplace well-being and whether their preclinical academic
      performance can be a trait-relevant situation that enhances their CSE expression.
      In total, 127 medical students from 2 cohorts were included as participants in
      this study. We analyzed complete measures of personal background, objective and
      subjective preclinical academic performance (course evaluation grades and self
      reported efficacy), CSE tendencies, and clinical competence (as objective
      structured clinical examination scores) and workplace well-being (as compassion
      satisfaction and burnout) during their 2-year clerkship. Mixed linear models for
      repeated measures and multiple regressions were employed. Participants' CSE
      tendencies had positive effects on their workplace compassion satisfaction and
      burnout but not on their clinical competence during their clerkship.
      Additionally, using the objective and subjective preclinical academic performance
      of the medical students as indicators, we observed that neither could be trait
      relevant situations to enhance their CSE expression. CSE personality tendencies
      might be key to medical students' ability to noncognitively adapt to clinical
      training during their clerkships. These tendencies should be identified earlier
      so that mentors can provide prompt care and support to mentees (medical students)
      during clerkships.

PMID- 29186157
TI  - Finite element simulation and clinical follow-up of lumbar spine biomechanics
      with dynamic fixations.
AB  - Arthrodesis is a recommended treatment in advanced stages of degenerative disc
      disease. Despite dynamic fixations were designed to prevent abnormal motions with
      better physiological load transmission, improving lumbar pain and reducing stress
      on adjacent segments, contradictory results have been obtained. This study was
      designed to compare differences in the biomechanical behaviour between the
      healthy lumbar spine and the spine with DYNESYS and DIAM fixation, respectively,
      at L4-L5 level. Behaviour under flexion, extension, lateral bending and axial
      rotation are compared using healthy lumbar spine as reference. Three 3D finite
      element models of lumbar spine (healthy, DYNESYS and DIAM implemented,
      respectively) were developed, together a clinical follow-up of 58 patients
      operated on for degenerative disc disease. DYNESYS produced higher variations of
      motion with a maximum value for lateral bending, decreasing intradiscal pressure
      and facet joint forces at instrumented level, whereas screw insertion zones
      concentrated stress. DIAM increased movement during flexion, decreased it in
      another three movements, and produced stress concentration at the apophyses at
      instrumented level. Dynamic systems, used as single systems without vertebral
      fusion, could be a good alternative to degenerative disc disease for grade II and
      grade III of Pfirrmann.

PMID- 29186159
TI  - Predictors of seasonal influenza vaccination among older adults in Thailand.
AB  - BACKGROUND: In advance of a large influenza vaccine effectiveness (VE) cohort
      study among older adults in Thailand, we conducted a population-based, cross
      sectional survey to measure vaccine coverage and identify factors associated with
      influenza vaccination among older Thai adults that could bias measures of vaccine
      effectiveness. METHOD: We selected adults >=65 years using a two-stage,
      stratified, cluster sampling design. Functional status was assessed using the 10
      point Vulnerable Elders Survey (VES); scores >=3 indicated vulnerability.
      Questions about attitudes towards vaccination were based on the Health Belief
      Model. The distance between participants' households and the nearest vaccination
      clinic was calculated. Vaccination status was determined using national influenza
      vaccination registry. Prevalence ratios (PR) and 95% confidence intervals (CIs)
      were calculated using log-binomial multivariable models accounting for the
      sampling design. RESULT: We enrolled 581 participants, of whom 60% were female,
      median age was 72 years, 41% had at least one chronic underlying illness, 24% met
      the criteria for vulnerable, and 23% did not leave the house on a daily basis.
      Influenza vaccination rate was 34%. In multivariable models, no variable related
      to functional status was associated with vaccination. The strongest predictors of
      vaccination were distance to the nearest vaccination center (PR 3.0, 95% CI 1.7
      5.1 for participants in the closest quartile compared to the furthest), and high
      levels of a perception of benefits of influenza vaccination (PR 2.8, 95% CI 1.4
      5.6) and cues to action (PR 2.7, 95% CI 1.5-5.1). CONCLUSION: Distance to
      vaccination clinics should be considered in analyses of influenza VE studies in
      Thailand. Strategies that emphasize benefits of vaccination and encourage
      physicians to recommend annual influenza vaccination could improve influenza
      vaccine uptake among older Thai adults. Outreach to more distant and less mobile
      older adults may also be required to improve influenza vaccination coverage.

PMID- 29186160
TI  - Community detection in dynamic networks via adaptive label propagation.
AB  - An adaptive label propagation algorithm (ALPA) is proposed to detect and monitor
      communities in dynamic networks. Unlike the traditional methods by re-computing
      the whole community decomposition after each modification of the network, ALPA
      takes into account the information of historical communities and updates its
      solution according to the network modifications via a local label propagation
      process, which generally affects only a small portion of the network. This makes
      it respond to network changes at low computational cost. The effectiveness of
      ALPA has been tested on both synthetic and real-world networks, which shows that
      it can successfully identify and track dynamic communities. Moreover, ALPA could
      detect communities with high quality and accuracy compared to other methods.
      Therefore, being low-complexity and parameter-free, ALPA is a scalable and
      promising solution for some real-world applications of community detection in
      dynamic networks.

PMID- 29186161
TI  - Enhancing reproducibility in scientific computing: Metrics and registry for
      Singularity containers.
AB  - Here we present Singularity Hub, a framework to build and deploy Singularity
      containers for mobility of compute, and the singularity-python software with
      novel metrics for assessing reproducibility of such containers. Singularity
      containers make it possible for scientists and developers to package reproducible
      software, and Singularity Hub adds automation to this workflow by building,
      capturing metadata for, visualizing, and serving containers programmatically. Our
      novel metrics, based on custom filters of content hashes of container contents,
      allow for comparison of an entire container, including operating system, custom
      software, and metadata. First we will review Singularity Hub's primary use cases
      and how the infrastructure has been designed to support modern, common workflows.
      Next, we conduct three analyses to demonstrate build consistency, reproducibility
      metric and performance and interpretability, and potential for discovery. This is
      the first effort to demonstrate a rigorous assessment of measurable similarity
      between containers and operating systems. We provide these capabilities within
      Singularity Hub, as well as the source software singularity-python that provides
      the underlying functionality. Singularity Hub is available at https://singularity
      hub.org, and we are excited to provide it as an openly available platform for
      building, and deploying scientific containers.

PMID- 29186162
TI  - Pore-forming activity of new conjugate antibiotics based on amphotericin B.
AB  - A series of amides of the antifungal antibiotic amphotericin B (AmB) and its
      conjugates with benzoxaboroles was tested to determine whether they form pores in
      lipid bilayers and to compare their channel characteristics. The tested
      derivatives produced pores of larger amplitude and shorter lifetime than those of
      the parent antibiotic. The pore conductance was related to changes in the partial
      charge of the hydrogens of the hydroxyl groups in the lactone ring that
      determined the anion coordination in the channel. Neutralization of one of the
      polar group charges in the AmB head during chemical modification produced a
      pronounced effect by diminishing the dwell time of the polyene channel compared
      to modification of both groups. In this study, compounds that had a modification
      of one carboxyl or amino group were less effective in initializing phase
      separation in POPC-membranes compared to derivatives that had modifications of
      both polar groups as well as the parent antibiotic. The effects were attributed
      to the restriction of the aggregation process by electrical repulsion between
      charged derivatives in contrast to neutral compounds. The significant correlation
      between the ability of derivatives to increase the permeability of model
      membranes-causing the appearance of single channels in lipid bilayers or inducing
      calcein leakage from unilamellar vesicles-and the minimal inhibitory
      concentration indicated that the antifungal effect of the conjugates was due to
      pore formation in the membranes of target cells.

PMID- 29186163
TI  - Development and validation of a tool to assess knowledge and attitudes towards
      generic medicines among students in Greece: The ATtitude TOwards GENerics
      (ATTOGEN) questionnaire.
AB  - INTRODUCTION: The use of generic medicines is a cost-effective policy, often
      dictated by fiscal restraints. To our knowledge, no fully validated tool
      exploring the students' knowledge and attitudes towards generic medicines exists.
      The aim of our study was to develop and validate a questionnaire exploring the
      knowledge and attitudes of M.Sc. in Health Care Management students and recent
      alumni's towards generic drugs in Greece. MATERIALS AND METHODS: The development
      of the questionnaire was a result of literature review and pilot-testing of its
      preliminary versions to researchers and students. The final version of the
      questionnaire contains 18 items measuring the respondents' knowledge and attitude
      towards generic medicines on a 5-point Likert scale. Given the ordinal nature of
      the data, ordinal alpha and polychoric correlations were computed. The sample was
      randomly split into two halves. Exploratory factor analysis, performed in the
      first sample, was used for the creation of multi-item scales. Confirmatory factor
      analysis and Generalized Linear Latent and Mixed Model analysis (GLLAMM) with the
      use of the rating scale model were used in the second sample to assess goodness
      of fit. An assessment of internal consistency reliability, test-retest
      reliability, and construct validity was also performed. RESULTS: Among 1402
      persons contacted, 986 persons completed our questionnaire (response rate =
      70.3%). Overall Cronbach's alpha was 0.871. The conjoint use of exploratory and
      confirmatory factor analysis resulted in a six-scale model, which seemed to fit
      the data well. Five of the six scales, namely trust, drug quality, state audit,
      fiscal impact and drug substitution were found to be valid and reliable, while
      the knowledge scale suffered only from low inter-scale correlations and a ceiling
      effect. However, the subsequent confirmatory factor and GLLAMM analyses indicated
      a good fit of the model to the data. CONCLUSIONS: The ATTOGEN instrument proved
      to be a reliable and valid tool, suitable for assessing students' knowledge and
      attitudes towards generic medicines.

PMID- 29186164
TI  - A retrospective matched cohort study evaluating the effects of percutaneous
      endoscopic gastrostomy feeding tubes on nutritional status and survival in
      patients with advanced gastroesophageal malignancies undergoing systemic anti
      cancer therapy.
AB  - BACKGROUND: Many patients with cancer or other systemic illnesses can experience
      malnutrition. One way to mitigate malnutrition is by insertion of a percutaneous
      endoscopic gastrostomy feeding tube (PEG tube). The goal of this retrospective
      matched cohort study is to evaluate if PEG tube placement improved nutritional
      status and overall survival (OS) in advanced gastroesophageal (GE) cancer
      patients who are undergoing anti-neoplastic therapy. METHODS: GE cancer patients
      who were treated and evaluated by a nutritionist and had at least 2 nutritionist
      follow-up visits were identified. Patients with PEG tube were matched to patients
      that did not undergo PEG placement (non-PEG). Clinical characteristics, GE
      symptoms reported at nutrition follow-up visits, and OS were recorded. RESULTS:
      20 PEG and 18 non-PEG cases met criteria for further analyses. After correction
      for multiple testing, there were no OS differences between PEG and non-PEG,
      treatment naive and previously treated. However, PEG esophageal carcinoma has
      statistically significant inferior OS compared with non-PEG esophageal carcinoma.
      PEG placement did not significantly reduce the proportion of patients with weight
      loss between the initial nutrition assessment and 12-week follow-up. CONCLUSIONS:
      In this small study, PEG placement had inferior OS outcome for GE esophageal
      carcinoma, no improvement in OS for other evaluated groups, and did not reduce
      weight loss between baseline and 12-week follow-up. Unless there is prospective
      randomized trial that can show superiority of PEG placement in this population,
      PEG placement in this group cannot be endorsed.

PMID- 29186165
TI  - Disentangling the influence of living place and socioeconomic position on health
      services use among diabetes patients: A population-based study.
AB  - This research investigates the influence of place of residence and diabetic
      patient's socioeconomic position on their use of health services in a universal
      health care system. This retrospective cross-sectional population-based study is
      based on the joint use of the Health Insurance information systems, an ecological
      indicator of social deprivation and an indicator of potential spatial
      accessibility of healthcare provision in the Midi-Pyrenees region. Using French
      healthcare insurance population-based data on reimbursement of out-of-hospital
      care during the year 2012, we study the use of health services among patients
      aged 50 and over (n = 90,136).We built logistic regression models linking health
      services use to socioeconomic position by geographic area, adjusted for age,
      gender, healthcare provision, information regarding patients precariousness, and
      long-term condition, used as proxy for the state of health. After adjustment for
      healthcare provision, the lower population density in the geographical area of
      concern, the lower the access to specialised care, independent of the patients'
      SEP. General practitioner attendance was higher among the patients with the
      lowest SEP without being clearly influenced by their living place. We found no
      clear influence of either patients' SEP or their living place on their access to
      biological follow-up. This study is an attempt to account for the geographical
      context and to go further in studying the social determinants of health among
      diabetes patients.

PMID- 29186166
TI  - Multi-AUV autonomous task planning based on the scroll time domain quantum bee
      colony optimization algorithm in uncertain environment.
AB  - Research on distributed task planning model for multi-autonomous underwater
      vehicle (MAUV). A scroll time domain quantum artificial bee colony (STDQABC)
      optimization algorithm is proposed to solve the multi-AUV optimal task planning
      scheme. In the uncertain marine environment, the rolling time domain control
      technique is used to realize a numerical optimization in a narrowed time range.
      Rolling time domain control is one of the better task planning techniques, which
      can greatly reduce the computational workload and realize the tradeoff between
      AUV dynamics, environment and cost. Finally, a simulation experiment was
      performed to evaluate the distributed task planning performance of the scroll
      time domain quantum bee colony optimization algorithm. The simulation results
      demonstrate that the STDQABC algorithm converges faster than the QABC and ABC
      algorithms in terms of both iterations and running time. The STDQABC algorithm
      can effectively improve MAUV distributed tasking planning performance, complete
      the task goal and get the approximate optimal solution.

PMID- 29186167
TI  - Deployment-based lifetime optimization for linear wireless sensor networks
      considering both retransmission and discrete power control.
AB  - A sophisticated method for node deployment can efficiently reduce the energy
      consumption of a Wireless Sensor Network (WSN) and prolong the corresponding
      network lifetime. Pioneers have proposed many node deployment based lifetime
      optimization methods for WSNs, however, the retransmission mechanism and the
      discrete power control strategy, which are widely used in practice and have large
      effect on the network energy consumption, are often neglected and assumed as a
      continuous one, respectively, in the previous studies. In this paper, both
      retransmission and discrete power control are considered together, and a more
      realistic energy-consumption-based network lifetime model for linear WSNs is
      provided. Using this model, we then propose a generic deployment-based
      optimization model that maximizes network lifetime under coverage, connectivity
      and transmission rate success constraints. The more accurate lifetime evaluation
      conduces to a longer optimal network lifetime in the realistic situation. To
      illustrate the effectiveness of our method, both one-tiered and two-tiered
      uniformly and non-uniformly distributed linear WSNs are optimized in our case
      studies, and the comparisons between our optimal results and those based on
      relatively inaccurate lifetime evaluation show the advantage of our method when
      investigating WSN lifetime optimization problems.

PMID- 29186168
TI  - Quantitative evaluation of age-related decline in control of preprogramed
      movement.
AB  - In this paper, we examined the age-related changes in control of preprogramed
      movement, with emphasis on its accuracy. Forty-nine healthy subjects participated
      in this study, and were divided into three groups depending on their ages: the
      young group (20-39 years) (n = 16), the middle-age group (40-59 years) (n = 16),
      and the elderly group (60-79 years) (n = 17). We asked the subjects to perform
      step-tracking movements of the wrist joint with a manipulandum, and recorded the
      movements. We evaluated the accuracy of control of preprogramed movement in the
      three groups in terms of the primary submovement, which was identified as the
      first segment of the step-tracking movement based on the bell-shaped velocity
      profile, and calculated the distance between the end position of the primary
      submovement and the target (i.e. error). The error in the young group was found
      to be significantly smaller than that in the middle-age and elderly groups, i.e.,
      the error was larger for the higher age groups. These results suggest that young
      subjects have better control of preprogramed movement than middle-age or elderly
      subjects. Finally, we examined the temporal property of the primary submovement
      and its age-related changes. The duration of the primary submovement tended to be
      longer for the aged groups, although significance was reached only for the
      elderly group. In particular, the ratio of the duration of the primary
      submovement to total movement time tended to be lower for the aged groups,
      suggesting that the proportion of additional movements that are required to
      compensate for the incomplete control in the preprogramed movement, which are
      under feedback control, was higher for the aged groups. Consequently, our results
      indicate that the distance between the end point of the primary submovement and
      the target center (i.e. error) in the step-tracking movement is a useful
      parameter to evaluate the age-related changes in control of preprogramed
      movement.

PMID- 29186169
TI  - Epidemiology of severe mental illness in Hunan province in central China during
      2014-2015: A multistage cross-sectional study.
AB  - OBJECTIVE: Severe mental illness (SMI) represents major social and public health
      problem in China, especially in low- or middle-income regions. We aim to assess
      the prevalence and distribution of SMI in Hunan province in central China.
      METHODS: Multistage stratified random sampling methods were used to select
      qualified subjects in 123 districts and counties in Hunan province. 89465
      individuals were randomly identified, and 72999 (81.6%) completed the
      supplemental 12-Item General Health Questionnaire (GHQ-12) and Cue questionnaire
      of psychiatric abnormal behaviors. 6082 suspected individuals having high or
      moderate risk, or psychiatric cues, were administered the Structured Clinical
      Interview for DSM-IV Axis I disorders (SCID-I) by psychiatrists. RESULTS: 720
      respondents were definitely diagnosed as SMI. The 1-month and lifetime prevalence
      was 9.350/00 and 10.100/00, respectively. The most frequent SMI was
      schizophrenia, followed by bipolar disorder, intellectual disability, epileptic
      mental disorder, paranoid psychosis and schizoaffective disorders, with 1-month
      prevalence ranging from 0.110/00 to 6.500/00 and lifetime prevalence ranging from
      0.240/00 to 6.860/00. Multivariate logistic regression analysis revealed that
      lower education, farmer occupation, retirees or jobless/unemployed, unmarried or
      divorced and age of 30-64 years old were major factors that associated with the
      increased risk of SMI. In addition, only 33.3% of 528 patients who completed
      questionnaire sought help in psychiatric institutions, and up to 51.7% of 720
      patients were not referred to the SMI management system in Hunan province.
      CONCLUSIONS: These findings provided a large-scale prevalence data of SMI in a
      provincial sample of China. The psychiatric disorders brought economical and
      psychological burden for family and society, which may shed light on the
      significance of scaling up province-wide mental health service and strengthening
      the SMI management.

PMID- 29186171
TI  - Analyzing cross-college course enrollments via contextual graph mining.
AB  - The ability to predict what courses a student may enroll in the coming semester
      plays a pivotal role in the allocation of learning resources, which is a hot
      topic in the domain of educational data mining. In this study, we propose an
      innovative approach to characterize students' cross-college course enrollments by
      leveraging a novel contextual graph. Specifically, different kinds of variables,
      such as students, courses, colleges and diplomas, as well as various types of
      variable relations, are utilized to depict the context of each variable, and then
      a representation learning algorithm node2vec is applied to extracting
      sophisticated graph-based features for the enrollment analysis. In this manner,
      the relations between any pair of variables can be measured quantitatively, which
      enables the variable type to transform from nominal to ratio. These graph-based
      features are examined by the random forest algorithm, and experiments on 24,663
      students, 1,674 courses and 417,590 enrollment records demonstrate that the
      contextual graph can successfully improve analyzing the cross-college course
      enrollments, where three of the graph-based features have significantly stronger
      impacts on prediction accuracy than the others. Besides, the empirical results
      also indicate that the student's course preference is the most important factor
      in predicting future course enrollments, which is consistent to the previous
      studies that acknowledge the course interest is a key point for course
      recommendations.

PMID- 29186170
TI  - Evaluating the versatility of EEG models generated from motor imagery tasks: An
      exploratory investigation on upper-limb elbow-centered motor imagery tasks.
AB  - Electroencephalography (EEG) has recently been considered for use in
      rehabilitation of people with motor deficits. EEG data from the motor imagery of
      different body movements have been used, for instance, as an EEG-based control
      method to send commands to rehabilitation devices that assist people to perform a
      variety of different motor tasks. However, it is both time and effort consuming
      to go through data collection and model training for every rehabilitation task.
      In this paper, we investigate the possibility of using an EEG model from one type
      of motor imagery (e.g.: elbow extension and flexion) to classify EEG from other
      types of motor imagery activities (e.g.: open a drawer). In order to study the
      problem, we focused on the elbow joint. Specifically, nine kinesthetic motor
      imagery tasks involving the elbow were investigated in twelve healthy individuals
      who participated in the study. While results reported that models from goal
      oriented motor imagery tasks had higher accuracy than models from the simple
      joint tasks in intra-task testing (e.g., model from elbow extension and flexion
      task was tested on EEG data collected from elbow extension and flexion task),
      models from simple joint tasks had higher accuracies than the others in inter
      task testing (e.g., model from elbow extension and flexion task tested on EEG
      data collected from drawer opening task). Simple single joint motor imagery tasks
      could, therefore, be considered for training models to potentially reduce the
      number of repetitive data acquisitions and model training in rehabilitation
      applications.

PMID- 29186172
TI  - Geometric calibration of a stationary digital breast tomosynthesis system based
      on distributed carbon nanotube X-ray source arrays.
AB  - Stationary digital breast tomosynthesis (sDBT) with distributed X-ray sources
      based on carbon nanotube (CNT) field emission cathodes has been recently proposed
      as an approach that can prevent motion blur produced by traditional DBT systems.
      In this paper, we simulate a geometric calibration method based on a proposed
      multi-source CNT X-ray sDBT system. This method is a projection matrix-based
      approach with seven geometric parameters, all of which can be obtained from only
      one projection datum of the phantom. To our knowledge, this study reports the
      first application of this approach in a CNT-based multi-beam X-ray sDBT system.
      The simulation results showed that the extracted geometric parameters from the
      calculated projection matrix are extremely close to the input values and that the
      proposed method is effective and reliable for a square sDBT system. In addition,
      a traditional cone-beam computed tomography (CT) system was also simulated, and
      the uncalibrated and calibrated geometric parameters were used in image
      reconstruction based on the filtered back-projection (FBP) method. The results
      indicated that the images reconstructed with calibrated geometric parameters have
      fewer artifacts and are closer to the reference image. All the simulation tests
      showed that this geometric calibration method is optimized for sDBT systems but
      can also be applied to other application-specific CT imaging systems.

PMID- 29186173
TI  - Reference-shaping adaptive control by using gradient descent optimizers.
AB  - This study presents a model reference adaptive control scheme based on reference
      shaping approach. The proposed adaptive control structure includes two optimizer
      processes that perform gradient descent optimization. The first process is the
      control optimizer that generates appropriate control signal for tracking of the
      controlled system output to a reference model output. The second process is the
      adaptation optimizer that performs for estimation of a time-varying adaptation
      gain, and it contributes to improvement of control signal generation. Numerical
      update equations derived for adaptation gain and control signal perform gradient
      descent optimization in order to decrease the model mismatch errors. To reduce
      noise sensitivity of the system, a dead zone rule is applied to the adaptation
      process. Simulation examples show the performance of the proposed Reference
      Shaping Adaptive Control (RSAC) method for several test scenarios. An
      experimental study demonstrates application of method for rotor control.

PMID- 29186174
TI  - Parallel arrangements of positive feedback loops limit cell-to-cell variability
      in differentiation.
AB  - Cellular differentiations are often regulated by bistable switches resulting from
      specific arrangements of multiple positive feedback loops (PFL) fused to one
      another. Although bistability generates digital responses at the cellular level,
      stochasticity in chemical reactions causes population heterogeneity in terms of
      its differentiated states. We hypothesized that the specific arrangements of PFLs
      may have evolved to minimize the cellular heterogeneity in differentiation. In
      order to test this we investigated variability in cellular differentiation
      controlled either by parallel or serial arrangements of multiple PFLs having
      similar average properties under extrinsic and intrinsic noises. We find that
      motifs with PFLs fused in parallel to one another around a central regulator are
      less susceptible to noise as compared to the motifs with PFLs arranged serially.
      Our calculations suggest that the increased resistance to noise in parallel
      motifs originate from the less sensitivity of bifurcation points to the extrinsic
      noise. Whereas estimation of mean residence times indicate that stable branches
      of bifurcations are robust to intrinsic noise in parallel motifs as compared to
      serial motifs. Model conclusions are consistent both in AND- and OR-gate input
      signal configurations and also with two different modeling strategies. Our
      investigations provide some insight into recent findings that differentiation of
      preadipocyte to mature adipocyte is controlled by network of parallel PFLs.

PMID- 29186175
TI  - Oral vocabulary training program for Spanish third-graders with low socio
      economic status: A randomized controlled trial.
AB  - Although the importance of vocabulary training in English speaking countries is
      well recognized and has been extensively studied, the same is not true for
      Spanish-few evidence based vocabulary studies for Spanish-speaking children have
      been reported. Here, two rich oral vocabulary training programs (definition and
      context), based on literature about vocabulary instruction for English-speaking
      children, were developed and applied in a sample of 100 Spanish elementary school
      third-graders recruited from areas of predominantly low socio-economic status
      (SES). Compared to an alternative read-aloud method which served as the control,
      both explicit methods were more effective in teaching word meanings when assessed
      immediately after the intervention. Nevertheless, five months later, only the
      definition group continued to demonstrate significant vocabulary knowledge gains.
      The definition method was more effective in specifically teaching children word
      meanings and, more broadly, in helping children organize and express knowledge of
      words. We recommend the explicit and rich vocabulary instruction as a means to
      fostering vocabulary knowledge in low SES children.

PMID- 29186176
TI  - Analysis of DNA topology of EBV minichromosomes in HEK 293 cells.
AB  - Simian Virus 40 (SV40) and Epstein-Barr Virus (EBV) are frequently used as model
      systems to study DNA replication. Their genomes are both circular duplex DNAs
      organized in a single replicon where replication initiates at a precise site upon
      binding of a specific protein: the large tumor (T) antigen for SV40 and the
      Epstein-Barr Nuclear Antigen 1 (EBNA-1) for EBV. Despite the abundant information
      available on the genetics and biochemistry of the replication process in these
      systems, little is known about the changes in DNA topology that take place as
      molecules are transfected into eukaryotic cells, assembled into chromatin and
      bind initiator proteins to start replication. Here we used high-resolution two
      dimensional agarose gel electrophoresis to demonstrate that in Human Embryonic
      Kidney (HEK) 293 cells, minichromosomes of almost the same mass carrying either
      the SV40 or the EBV replication origin showed similar topological features. The
      patterns were very similar regardless of the initiator proteins. We also showed
      that in a hybrid minichromosome, pEco3'Delta, that initiates replication from the
      SV40 origin, the presence of EBNA-1 and its putative binding to the EBV "family
      of repeats" induces no significant topological change. These observations
      challenge the idea that binding of EBNA-1 to oriP could induce negative
      supercoiling and favor a model suggesting that it binds to oriP in a two-step
      process where only the second step causes structural changes in a transient cell
      cycle specific manner.

PMID- 29186177
TI  - Intensive Care Syndrome: Promoting Independence and Return to Employment
      (InS:PIRE). Early evaluation of a complex intervention.
AB  - BACKGROUND: Many patients suffer significant physical, social and psychological
      problems in the months and years following critical care discharge. At present,
      there is minimal evidence of any effective interventions to support this patient
      group following hospital discharge. The aim of this project was to understand the
      impact of a complex intervention for ICU survivors. METHODS: Quality improvement
      project conducted between September 2014 and June 2016, enrolling 49 selected
      patients from one ICU in Scotland. To evaluate the impact of this programme
      outcomes were compared to an existing cohort of patients from the same ICU from
      2008-2009. Patients attended a five week peer supported rehabilitation programme.
      This multidisciplinary programme included pharmacy, physiotherapy, nursing,
      medical, and psychology input. The primary outcome in this evaluation was the EQ
      5D, a validated measure of health-related quality of life. The minimally
      clinically important difference (MCID) in the EQ-5D is 0.08. We also measured
      change in self-efficacy over the programme duration. Based on previous research,
      this study utilised a 2.4 (6%) point change in self-efficacy scores as a MCID.
      RESULTS: 40 patients (82%) completed follow-up surveys at 12 months. After
      regression adjustment for those factors known to impact recovery from critical
      care, there was a 0.07-0.16 point improvement in quality of life for those
      patients who took part in the intervention compared to historical controls from
      the same institution, depending on specific regression strategy used. Self
      efficacy scores increased by 2.5 points (6.25%) over the duration of the five
      week programme (p = 0.003), and was sustained at one year post intervention. In
      the year following ICU, 15 InS:PIRE patients returned to employment or
      volunteering roles (88%) compared with 11 (46%) in the historical control group
      (p = 0.15). CONCLUSIONS AND RELEVANCE: This historical control study suggests
      that a complex intervention may improve quality of life and self-efficacy in
      survivors of ICU. A larger, multi-centre study is needed to investigate this
      intervention further.

PMID- 29186178
TI  - Masticatory jaw movement of Exaeretodon argentinus (Therapsida: Cynodontia)
      inferred from its dental microwear.
AB  - Dental microwear of four postcanine teeth of Exaeretodon argentinus was analyzed
      using both two dimensional (2D) and three dimensional (3D) methods to infer their
      masticatory jaw movements. Results of both methods were congruent, showing that
      linear microwear features (scratches) were well aligned and mostly directed to
      the antero-posterior direction in all four teeth examined. These findings support
      the palinal masticatory jaw movement, which was inferred in previous studies
      based on the observation of gross morphology of wear facets. In contrast, the
      lack of detection of lateral scratches confirmed the absence of the lateral jaw
      movement that was also proposed by a previous study. Considering previous
      microwear studies on cynodonts, palinal jaw movements observed in Exaeretodon
      evolved within cynognathian cynodonts from the fully orthal jaw movement of its
      basal member. Although there are currently only three studies of dental microwear
      of non-mammalian cynodonts including the present study, microwear analysis is a
      useful tool for the reconstruction of masticatory jaw movement and its future
      application to various cynodonts will shed light on the evolutionary process of
      jaw movement towards the mammalian condition in more detail.

PMID- 29186179
TI  - Nonword repetition in adults who stutter: The effects of stimuli stress and
      auditory-orthographic cues.
AB  - PURPOSE: Adults who stutter (AWS) are less accurate in their immediate repetition
      of novel phonological sequences compared to adults who do not stutter (AWNS). The
      present study examined whether manipulation of the following two aspects of
      traditional nonword repetition tasks unmask distinct weaknesses in phonological
      working memory in AWS: (1) presentation of stimuli with less-frequent stress
      patterns, and (2) removal of auditory-orthographic cues immediately prior to
      response. METHOD: Fifty-two participants (26 AWS, 26 AWNS) produced 12 bisyllabic
      nonwords in the presence of corresponding auditory-orthographic cues (i.e.,
      immediate repetition task), and the absence of auditory-orthographic cues (i.e.,
      short-term recall task). Half of each cohort (13 AWS, 13 AWNS) were exposed to
      the stimuli with high-frequency trochaic stress, and half (13 AWS, 13 AWNS) were
      exposed to identical stimuli with lower-frequency iambic stress. RESULTS: No
      differences in immediate repetition accuracy for trochaic or iambic nonwords were
      observed for either group. However, AWS were less accurate when recalling iambic
      nonwords than trochaic nonwords in the absence of auditory-orthographic cues.
      CONCLUSIONS: Manipulation of two factors which may minimize phonological demand
      during standard nonword repetition tasks increased the number of errors in AWS
      compared to AWNS. These findings suggest greater vulnerability in phonological
      working memory in AWS, even when producing nonwords as short as two syllables.

PMID- 29186180
TI  - Clonogenic, myogenic progenitors expressing MCAM/CD146 are incorporated as
      adventitial reticular cells in the microvascular compartment of human post-natal
      skeletal muscle.
AB  - Recent observation identifies subendothelial (mural) cells expressing MCAM, a
      specific system of clonogenic, self-renewing, osteoprogenitors (a.k.a,
      "mesenchymal stem cells") in the microvascular compartment of post-natal human
      bone marrow (BM). In this study, we used MCAM/CD146, as a marker to localize,
      isolate and assay subendothelial clonogenic cells from the microvasculature of
      postnatal human skeletal muscle. We show here that these cells share with their
      BM counterpart, anatomic position (subendothelial/adventitial) and ex vivo
      clonogenicity (CFU-Fs). When assayed under the stringent conditions, these cells
      display a high spontaneous myogenic potential (independent of co-culture with
      myoblasts or of in vivo fusion with local myoblasts), which is otherwise only
      attained in cultures of satellite cells. These muscle-derived mural cells
      activated a myogenic program in culture. Cultured CD146+ cells expressed the
      myogenic factors (Pax7, Pax3 and Myf5), NCAM/CD56, desmin as well as proteins
      characteristic of more advanced myogenic differentiation, such as myosin heavy
      chain. In vivo, these cells spontaneously generate myotubes and myofibrils. These
      data identify the anatomy and phenotype of a novel class of committed myogenic
      progenitor in human post-natal skeletal muscle of subendothelial cells associated
      with the abluminal surface of microvascular compartment distinct from satellite
      cells.

PMID- 29186181
TI  - Development of a homogenous high-throughput assay for inositol hexakisphosphate
      kinase 1 activity.
AB  - Inositol pyrophosphates have been implicated in a wide range of cellular
      processes. Inositol hexakisphosphate kinase 1 catalyzes the pyrophosphorylation
      of inositol hexakisphosphate into inositol 5-diphospho-1,2,3,4,6
      pentakisphosphate which is important in numerous areas of cell physiology such as
      DNA repair and glucose homeostasis. Furthermore, inositol 5-diphospho-1,2,3,4,6
      pentakisphosphate is implicated in the pathology of diabetes and other human
      diseases. As such there is a demonstrated need in the field for a robust chemical
      probe to better understand the role of inositol hexakisphosphate kinase 1 and
      inositol pyrophosphate in physiology and disease. To aid in this effort we
      developed a homogenous coupled bioluminescence assay for measuring inositol
      hexakisphosphate kinase 1 activity in a 384-well format (Z' = 0.62+/-0.05). Using
      this assay we were able to confirm the activity of a known inositol
      hexakisphosphate kinase 1 inhibitor N2-(m-trifluorobenzyl), N6-(p
      nitrobenzyl)purine. We also screened the Sigma library of pharmacologically
      active compounds at 10MUM concentration and found 24 hits. Two of the most potent
      compounds were found to have an IC50 less than 5MUM. The use of this high
      throughput assay will accelerate the field towards the discovery of a potent
      inositol hexakisphosphate kinase 1 inhibitor.

PMID- 29186182
TI  - Identification of a novel linear B-cell epitope in nonstructural protein 11 of
      porcine reproductive and respiratory syndrome virus that are conserved in both
      genotypes.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most
      economically important pathogens, that hinder the development of global pork
      industry. Its nonstructural protein 11 (nsp11), with the nidoviral uridylate
      specific endoribonuclease (NendoU) domain, is essential for PRRSV genome
      replication and it also contributes to host innate immunity suppression. However,
      the immunogenicity and immune structure of PRRSV nsp11 have not been well
      investigated yet. In this study, a monoclonal antibody (mAb), designated 3F9,
      that against nsp11 was generated. Subsequently, a series of partially overlapped
      fragments, covered the nsp1140-223aa, were expressed to test the reactivity with
      mAb 3F9, and the 111DCREY115 was found to be the core unit of the B-cell epitope
      recognized by mAb 3F9. Further investigation indicated that both genotype 1 and
      genotype 2 PRRSV can be recognized by mAb 3F9, due to the 111DCREY115 is
      conserved in both genotype virus. Meanwhile, this epitope, localized at the
      surface of nsp11 in 3D structure, is confirmed to be able to induce humoral
      immune response in PRRSV infected pigs. These findings do not only provide an mAb
      tool to further investigate the function of nsp11, they also indicate the
      diagnostic potential for this epitope.

PMID- 29186183
TI  - A tool for simulating collision probabilities of animals with marine renewable
      energy devices.
AB  - The mathematical problem of establishing a collision probability distribution is
      often not trivial. The shape and motion of the animal as well as of the the
      device must be evaluated in a four-dimensional space (3D motion over time).
      Earlier work on wind and tidal turbines was limited to a simplified two
      dimensional representation, which cannot be applied to many new structures. We
      present a numerical algorithm to obtain such probability distributions using
      transient, three-dimensional numerical simulations. The method is demonstrated
      using a sub-surface tidal kite as an example. Necessary pre- and post-processing
      of the data created by the model is explained, numerical details and potential
      issues and limitations in the application of resulting probability distributions
      are highlighted.

PMID- 29186184
TI  - Considerations on Visible Light Communication security by applying the Risk
      Matrix methodology for risk assessment.
AB  - Visible Light Communications (VLC) is a cutting edge technology for data
      communication that is being considered to be implemented in a wide range of
      applications such as Inter-vehicle communication or Local Area Network (LAN)
      communication. As a novel technology, some aspects of the implementation of VLC
      have not been deeply considered or tested. Among these aspects, security and its
      implementation may become an obstacle for VLCs broad usage. In this article, we
      have used the well-known Risk Matrix methodology to determine the relative risk
      that several common attacks have in a VLC network. Four examples: a War Driving,
      a Queensland alike Denial of Service, a Preshared Key Cracking, and an Evil Twin
      attack, illustrate the utilization of the methodology over a VLC implementation.
      The used attacks also covered the different areas delimited by the attack
      taxonomy used in this work. By defining and determining which attacks present a
      greater risk, the results of this work provide a lead into which areas should be
      invested to increase the safety of VLC networks.

PMID- 29186185
TI  - Cost-effectiveness of different strategies for diagnosis of uncomplicated urinary
      tract infections in women presenting in primary care.
AB  - BACKGROUND: Uncomplicated Urinary Tract Infections (UTIs) are common in primary
      care resulting in substantial costs. Since antimicrobial resistance against
      antibiotics for UTIs is rising, accurate diagnosis is needed in settings with low
      rates of multidrug-resistant bacteria. OBJECTIVE: To compare the cost
      effectiveness of different strategies to diagnose UTIs in women who contacted
      their general practitioner (GP) with painful and/or frequent micturition between
      2006 and 2008 in and around Amsterdam, The Netherlands. METHODS: This is a model
      based cost-effectiveness analysis using data from 196 women who underwent four
      tests: history, urine stick, sediment, dipslide, and the gold standard, a urine
      culture. Decision trees were constructed reflecting 15 diagnostic strategies
      comprising different parallel and sequential combinations of the four tests.
      Using the decision trees, for each strategy the costs and the proportion of women
      with a correct positive or negative diagnosis were estimated. Probabilistic
      sensitivity analysis was used to estimate uncertainty surrounding costs and
      effects. Uncertainty was presented using cost-effectiveness planes and
      acceptability curves. RESULTS: Most sequential testing strategies resulted in
      higher proportions of correctly classified women and lower costs than parallel
      testing strategies. For different willingness to pay thresholds, the most cost
      effective strategies were: 1) performing a dipstick after a positive history for
      thresholds below ?10 per additional correctly classified patient, 2) performing
      both a history and dipstick for thresholds between ?10 and ?17 per additional
      correctly classified patient, 3) performing a dipstick if history was negative,
      followed by a sediment if the dipstick was negative for thresholds between ?17
      and ?118 per additional correctly classified patient, 4) performing a dipstick if
      history was negative, followed by a dipslide if the dipstick was negative for
      thresholds above ?118 per additional correctly classified patient. CONCLUSION:
      Depending on decision makers' willingness to pay for one additional correctly
      classified woman, the strategy consisting of performing a history and dipstick
      simultaneously (ceiling ratios between ?10 and ?17) or performing a sediment if
      history and subsequent dipstick are negative (ceiling ratios between ?17 and
      ?118) are the most cost-effective strategies to diagnose a UTI.

PMID- 29186187
TI  - Correction: pFAK-Y397 overexpression as both a prognostic and a predictive
      biomarker for patients with metastatic osteosarcoma.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0182989.].

PMID- 29186186
TI  - Application of non-invasive low strength pulsed electric field to EGCG treatment
      synergistically enhanced the inhibition effect on PANC-1 cells.
AB  - Traditional therapies for pancreatic cancer are usually expensive and likely to
      cause side effects, and most patients have the risk of recurrence and suffering
      pain. Here, we investigated combination treatment of epigallocatechin-3-gallate
      (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human
      pancreatic cell line PANC-1. Cells were cultured in various concentrations of
      EGCG and exposed to trains of PEF. The results showed that the low strength PEF
      alone or single treatment with low concentration of EGCG did not obviously affect
      the cell proliferation and migration in PANC-1. However, the EGCG-induced
      inhibitions of cell viability and migration ability in PANC-1 were dramatically
      enhanced by the further exposure of low strength PEF (60 V/cm). In particular,
      the same combination treatment caused less inhibition of cell viability in non
      malignant HEK293 cells. We also found the combination treatment significantly
      decreased the ratio of Bcl-2/Bax protein and increased caspase activity in PANC-1
      cells, resulting in the promotion of apoptotic responses, evidenced by chromatin
      condensation. The findings of the present study reveal the synergistic reactions
      in the combination treatment may severely disturb mitochondria, enhance the
      intrinsic pathway transduction, and effectively induce apoptosis; moreover, the
      migration and invasion of PANC-1 cancer cells were also significantly suppressed.
      Since normal cells are less sensitive to this combination treatment, and the non
      invasive PEF could be modified to focus on a specific location, this treatment
      may serve as a promising method for anti-cancer therapy.

PMID- 29186189
TI  - Modulation of corticospinal output in agonist and antagonist proximal arm muscles
      during motor preparation.
AB  - Previous studies have shown modulation of corticospinal output of the agonist
      muscle when a known-movement is prepared but withheld until a response signal
      appearance, reflecting motor preparation processes. However, modulation in the
      antagonist muscles has not been described, despite the fact that reaching
      movements require precise coordination between the activation of agonist and
      antagonist muscles. In this study, participants performed an instructed-delay
      reaction time (RT) task, with randomized elbow flexion and extension movements.
      The aim was to assess the time course modulation of corticospinal output in two
      antagonist muscles, by simultaneously quantified the amplitude of motor evoked
      potentials (MEPs) in biceps brachii and triceps brachii, and the amplitude and
      direction of elbow movements evoked by transcranial magnetic stimulation (TMS).
      Depending on the prepared movement direction, a specific modulation of
      corticospinal output was observed, MEPs and TMS-evoked movements amplitude being
      relatively greater for extension compared to flexion. At the end of motor
      preparation, a decrease in MEPs amplitude was observed for both biceps brachii
      and triceps brachii, regardless of the prepared movement direction. In contrast,
      the probability of evoking movement in the flexion direction and the amplitude of
      TMS-evoked movement decreased at the end of preparation for flexion, but not for
      extension. Together, these results confirm the existence of inhibitory processes
      at the end of the motor preparation, probably to avoid a premature motor
      response. Moreover, they provide evidence of differences in the corticospinal
      control of elbow flexor and extensor muscles with patterns of modulation that are
      not necessarily reciprocal during motor preparation.

PMID- 29186190
TI  - The sentinel tree nursery as an early warning system for pathway risk assessment:
      Fungal pathogens associated with Chinese woody plants commonly shipped to Europe.
AB  - Introduction of and invasion by alien plant pathogens represents the main cause
      of emerging infectious diseases affecting domesticated and wild plant species
      worldwide. The trade in living plants is the most common pathway of introduction.
      Many of the alien tree pathogens recently introduced into Europe were not
      previously included on any quarantine lists. To help determine the potential risk
      of pest introduction through trading of ornamental plants, a sentinel nursery was
      established in Beijing, China in 2008. The sentinel nursery planting included
      four of the most common ornamental woody species shipped to Europe including Ilex
      cornuta var. fortunae, Zelkova schneideriana, Fraxinus chinensis and Buxus
      microphylla. Symptoms developing on these species within the sentinel nursery
      were detected in 2013 and consisted of necrotic spots on leaves, canker and stem
      necrosis, shoot blight and shoot necrosis. Fungi associated with the trees and
      their symptoms included Alternaria alternata detected from all hosts; Diaporthe
      liquidambaris and Diaporthe capsici from bark and leaf necrosis of Zelkova
      schneideriana; Botryosphaeria dothidea and Nothophoma quercina from stem cankers
      on Fraxinus chinensis and leaf necrosis on Ilex cornuta; and Pseudonectria
      foliicola from leaf necrosis on Buxus microphylla. Next generation sequencing
      analysis from asymptomatic tissues detected eighteen OTU's at species level among
      which some taxa had not been previously recorded in Europe. These results clearly
      demonstrate that looking at trees of internationally traded species in the region
      of origin can reveal the presence of potentially harmful organisms of major
      forestry, landscape or crop trees. Results of this study also provide an
      indication as to how some disease agents can be introduced using pathways other
      than the co-generic hosts. Hence, sentinel nurseries represent one potential
      mechanism to address the current lack of knowledge about pests in the countries
      from where live plants are shipped and the threats they represent to native flora
      and crops in importing countries.

PMID- 29186188
TI  - Effect of age on chronic inflammation and responsiveness to bacterial and viral
      challenges.
AB  - To identify reliable biomarkers of age-related changes in chronic inflammation
      and responsiveness to bacterial and viral challenges, we evaluated endogenous and
      ex vivo stimulated levels of 18 inflammatory markers, using whole blood collected
      in EDTA and sodium heparin tubes from 41 healthy volunteers, i.e., 11 men + 10
      women aged 20-35 and 10 men + 10 women aged 50-77. These studies revealed
      significant differences in the levels of inflammatory markers when blood was
      collected in EDTA versus sodium heparin and age related differences in these
      biomarkers were confirmed with blood collected in EDTA from 120 healthy
      volunteers in 3 age categories, ie, 20 men + 20 women, aged 20-35, 36-49 and 50
      77. Studies with unstimulated blood samples, to measure levels of chronic
      inflammation, revealed a significant increase with age in IL-12p70, CRP and PGE2,
      consistent with the concept of "inflammaging", and a decrease in G-CSF in both
      men and women. Interestingly, in response to E. coli stimulation, PGE2 levels
      were markedly reduced in the 50-77 year old cohort while they were increased
      following Herpes Simplex virus-1 (HSV-1) stimulation, along with IL-8. In
      addition, unlike E. coli, HSV-1 potently stimulated IFNalpha production, but
      levels were dramatically reduced in the older cohort, consistent with a reduced
      ability to generate an anti-viral response. We also found platelets and CD8+ T
      cells were reduced with age while CD4+ T cells were significantly increased,
      resulting in a substantially higher CD4/CD8 ratio in the older cohort.
      Surprisingly, however, we found that the older cohort exhibited more T cell
      proliferation and IFNgamma production in response to anti-CD3+anti-CD28
      stimulation. Importantly, there was considerable person-to-person variation in
      these inflammatory markers in all age groups, making possible comparisons between
      a person's "inflammage" and chronological age. These assays should help to
      identify individuals at high risk of autoimmune disorders and cancer.

PMID- 29186192
TI  - Development of a GAL4-VP16/UAS trans-activation system for tissue specific
      expression in Medicago truncatula.
AB  - Promoters with tissue-specific activity are very useful to address cell
      autonomous and non cell autonomous functions of candidate genes. Although this
      strategy is widely used in Arabidopsis thaliana, its use to study tissue-specific
      regulation of root symbiotic interactions in legumes has only started recently.
      Moreover, using tissue specific promoter activity to drive a GAL4-VP16 chimeric
      transcription factor that can bind short upstream activation sequences (UAS) is
      an efficient way to target and enhance the expression of any gene of interest.
      Here, we developed a collection of promoters with different root cell layers
      specific activities in Medicago truncatula and tested their abilities to drive
      the expression of a chimeric GAL4-VP16 transcription factor in a trans-activation
      UAS: beta-Glucuronidase (GUS) reporter gene system. By developing a binary vector
      devoted to modular Golden Gate cloning together with a collection of adapted
      tissue specific promoters and coding sequences we could test the activity of four
      of these promoters in trans-activation GAL4/UAS systems and compare them to
      "classical" promoter GUS fusions. Roots showing high levels of tissue specific
      expression of the GUS activity could be obtained with this trans-activation
      system. We therefore provide the legume community with new tools for efficient
      modular Golden Gate cloning, tissue specific expression and a trans-activation
      system. This study provides the ground work for future development of stable
      transgenic lines in Medicago truncatula.

PMID- 29186191
TI  - Lipopolysaccharide structure impacts the entry kinetics of bacterial outer
      membrane vesicles into host cells.
AB  - Outer membrane vesicles are nano-sized microvesicles shed from the outer membrane
      of Gram-negative bacteria and play important roles in immune priming and disease
      pathogenesis. However, our current mechanistic understanding of vesicle-host cell
      interactions is limited by a lack of methods to study the rapid kinetics of
      vesicle entry and cargo delivery to host cells. Here, we describe a highly
      sensitive method to study the kinetics of vesicle entry into host cells in real
      time using a genetically encoded, vesicle-targeted probe. We found that the route
      of vesicular uptake, and thus entry kinetics and efficiency, are shaped by
      bacterial cell wall composition. The presence of lipopolysaccharide O antigen
      enables vesicles to bypass clathrin-mediated endocytosis, which enhances both
      their entry rate and efficiency into host cells. Collectively, our findings
      highlight the composition of the bacterial cell wall as a major determinant of
      secretion-independent delivery of virulence factors during Gram-negative
      infections.

PMID- 29186193
TI  - RIG-I-like receptor activation by dengue virus drives follicular T helper cell
      formation and antibody production.
AB  - Follicular T helper cells (TFH) are fundamental in orchestrating effective
      antibody-mediated responses critical for immunity against viral infections and
      effective vaccines. However, it is unclear how virus infection leads to TFH
      induction. We here show that dengue virus (DENV) infection of human dendritic
      cells (DCs) drives TFH formation via crosstalk of RIG-I-like receptor (RLR) RIG-I
      and MDA5 with type I Interferon (IFN) signaling. DENV infection leads to RLR
      dependent IKKepsilon activation, which phosphorylates IFNalpha/beta receptor
      induced STAT1 to drive IL-27 production via the transcriptional complex ISGF3.
      Inhibiting RLR activation as well as neutralizing antibodies against IL-27
      prevented TFH formation. DENV-induced CXCR5+PD-1+Bcl-6+ TFH cells secreted IL-21
      and activated B cells to produce IgM and IgG. Notably, RLR activation by
      synthetic ligands also induced IL-27 secretion and TFH polarization. These
      results identify an innate mechanism by which antibodies develop during viral
      disease and identify RLR ligands as potent adjuvants for TFH-promoting
      vaccination strategies.

PMID- 29186195
TI  - Assemblies of amyloid-beta30-36 hexamer and its G33V/L34T mutants by replica
      exchange molecular dynamics simulation.
AB  - The aggregation of amyloid-beta peptides is associated with the pathogenesis of
      Alzheimer's disease, in which the 30-36 fragments play an important part as a
      fiber-forming hydrophobic region. The fibrillar structure of Abeta30-36 has been
      detected by means of X-ray diffraction, but its oligomeric structural
      determination, biophysical characterization, and pathological mechanism remain
      elusive. In this study, we have investigated the structures of Abeta30-36 hexamer
      as well as its G33V and L34T mutants in explicit water environment using replica
      exchange molecular dynamics (REMD) simulations. Our results show that the wild
      type (WT) Abeta30-36 hexamer has a preference to form beta-barrel and bilayer
      beta-sheet conformations, while the G33V or L34T mutation disrupts the beta
      barrel structures: the G33V mutant is homogenized to adopt beta-sheet-rich
      bilayers, and the structures of L34T mutant on the contrary get more diverse. The
      hydrophobic interaction plays a critical role in the formation and stability of
      oligomeric assemblies among all the three systems. In addition, the substitution
      of G33 by V reduces the beta-sheet content in the most populated conformations of
      Abeta30-36 oligomers through a steric effect. The L34T mutation disturbs the
      interpeptide hydrogen bonding network, and results in the increased coil content
      and morphological diversity. Our REMD runs provide structural details of WT and
      G33V/L34T mutant Abeta30-36 oligomers, and molecular insight into the aggregation
      mechanism, which will be helpful for designing novel inhibitors or amyloid-based
      materials.

PMID- 29186194
TI  - Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells
      in vivo.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) infects mainly CD4+CCR4+
      effector/memory T cells in vivo. However, it remains unknown whether HTLV-1
      preferentially infects these T cells or this virus converts infected precursor
      cells to specialized T cells. Expression of viral genes in vivo is critical to
      study viral replication and proliferation of infected cells. Therefore, we first
      analyzed viral gene expression in non-human primates naturally infected with
      simian T-cell leukemia virus type 1 (STLV-1), whose virological attributes
      closely resemble those of HTLV-1. Although the tax transcript was detected only
      in certain tissues, Tax expression was much higher in the bone marrow, indicating
      the possibility of de novo infection. Furthermore, Tax expression of non-T cells
      was suspected in bone marrow. These data suggest that HTLV-1 infects
      hematopoietic cells in the bone marrow. To explore the possibility that HTLV-1
      infects hematopoietic stem cells (HSCs), we analyzed integration sites of HTLV-1
      provirus in various lineages of hematopoietic cells in patients with HTLV-1
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a HTLV-1 carrier
      using the high-throughput sequencing method. Identical integration sites were
      detected in neutrophils, monocytes, B cells, CD8+ T cells and CD4+ T cells,
      indicating that HTLV-1 infects HSCs in vivo. We also detected Tax protein in
      myeloperoxidase positive neutrophils. Furthermore, dendritic cells differentiated
      from HTLV-1 infected monocytes caused de novo infection to T cells, indicating
      that infected monocytes are implicated in viral spreading in vivo. Certain
      integration sites were re-detected in neutrophils from HAM/TSP patients at
      different time points, indicating that infected HSCs persist and differentiate in
      vivo. This study demonstrates that HTLV-1 infects HSCs, and infected stem cells
      differentiate into diverse cell lineages. These data indicate that infection of
      HSCs can contribute to the persistence and spread of HTLV-1 in vivo.

PMID- 29186196
TI  - The integration of probabilistic information during sensorimotor estimation is
      unimpaired in children with Cerebral Palsy.
AB  - BACKGROUND: It is important to understand the motor deficits of children with
      Cerebral Palsy (CP). Our understanding of this motor disorder can be enriched by
      computational models of motor control. One crucial stage in generating movement
      involves combining uncertain information from different sources, and deficits in
      this process could contribute to reduced motor function in children with CP.
      Healthy adults can integrate previously-learned information (prior) with incoming
      sensory information (likelihood) in a close-to-optimal way when estimating object
      location, consistent with the use of Bayesian statistics. However, there are few
      studies investigating how children with CP perform sensorimotor integration. We
      compare sensorimotor estimation in children with CP and age-matched controls
      using a model-based analysis to understand the process. METHODS AND FINDINGS: We
      examined Bayesian sensorimotor integration in children with CP, aged between 5
      and 12 years old, with Gross Motor Function Classification System (GMFCS) levels
      1-3 and compared their estimation behavior with age-matched typically-developing
      (TD) children. We used a simple sensorimotor estimation task which requires
      participants to combine probabilistic information from different sources: a
      likelihood distribution (current sensory information) with a prior distribution
      (learned target information). In order to examine sensorimotor integration, we
      quantified how participants weighed statistical information from the two sources
      (prior and likelihood) and compared this to the statistical optimal weighting. We
      found that the weighing of statistical information in children with CP was as
      statistically efficient as that of TD children. CONCLUSIONS: We conclude that
      Bayesian sensorimotor integration is not impaired in children with CP and
      therefore, does not contribute to their motor deficits. Future research has the
      potential to enrich our understanding of motor disorders by investigating the
      stages of motor processing set out by computational models. Therapeutic
      interventions should exploit the ability of children with CP to use statistical
      information.

PMID- 29186197
TI  - Fingolimod suppresses neuronal autophagy through the mTOR/p70S6K pathway and
      alleviates ischemic brain damage in mice.
AB  - The bioactive, signaling lipid, sphingosine-1-phosphate (S1P), and its analog,
      fingolimod (FTY720), have previously shown neuroprotective effects against
      ischemic brain injury. However, the underlying mechanisms have not yet been fully
      clarified. The roles of autophagy in ischemic stroke are being increasingly
      recognized. In the present study, we sought to determine whether the S1P pathway
      is involved in neuronal autophagy and investigate its possible mechanisms
      following stroke. Interestingly, we found that FTY720 significantly attenuates
      infarct volumes and reduces neuronal apoptosis on days 1 and 3 post stroke,
      accompanied by amelioration of functional deficits. Additionally, FTY720 was
      found to decrease the induction of autophagosome proteins, microtubule-associated
      protein 1 light chain 3(LC3-II) and Beclin1, following ischemic stroke in a dose
      dependent manner. Meanwhile, protein levels of the mammalian target of rapamycin
      (mTOR) and the 70-kDa ribosomal protein, S6 kinase1 (p70S6K), were also up
      regulated in FTY720-treated animals, and the nonspecific SphK inhibitor, N,N
      dimethylsphingosine (DMS), was found to cause a reverse effect. Our results
      indicate that modulation of the S1P signaling pathway by FTY720 could effectively
      decrease neuronal autophagy through the mTOR/p70S6K pathway and attenuate
      ischemic brain injury in mice.

PMID- 29186198
TI  - Safety and efficacy of ferric citrate in patients with nondialysis-dependent
      chronic kidney disease.
AB  - Two randomized, placebo-controlled trials conducted in patients with nondialysis
      dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, and normal
      or elevated serum phosphorus demonstrated that ferric citrate (FC) significantly
      increased hemoglobin and decreased serum phosphate concentrations. Pooling these
      trial results could provide a more robust evaluation of the safety and efficacy
      of FC in this population. We pooled results of a phase 2 (n = 149) and 3 trial (n
      = 233) of patients randomized and treated for up to 12 and 16 weeks,
      respectively. The starting dose in both trials was three 1-g (elemental iron 210
      mg) tablets/day with food, up to 12 tablets/day. Doses were titrated in the phase
      2 and 3 trials to lower serum phosphate concentrations to a target range (0.97
      1.13 mmol/L) and to achieve a >=10-g/L hemoglobin increase, respectively. Safety
      was assessed in all patients who received >=1 dose of FC (n = 190) and placebo (n
      = 188). Treatment-emergent adverse events (AEs) were reported in 143 of 190
      (75.3%) FC-treated and 116 of 188 (61.7%) placebo-treated patients;
      gastrointestinal AEs were the most frequent (94 [49.5%] vs. 52 [27.7%],
      respectively). Specific events reported in >5% of patients (FC vs. placebo,
      respectively) included discolored feces (41 [21.6%] vs. 0 [0.0%]), diarrhea (39
      [20.5%] vs. 23 [12.2%]), constipation (35 [18.4%] vs. 19 [10.1%]), and nausea (18
      [9.5%] vs. 8 [4.3%]). Twenty FC-treated (10.5%) and 21 placebo-treated patients
      (11.2%) experienced a serious AE. Two patients (1.1%) died in each group. A
      pooled efficacy assessment demonstrated a consistent hemoglobin rise and modest
      serum phosphate decline, with few excursions below the normal range. When used
      for treatment of patients with NDD-CKD, FC contributes to gastrointestinal AEs at
      higher rates than placebo, while simultaneously correcting two of the principal
      metabolic manifestations of CKD (iron deficiency anemia and relative
      hyperphosphatemia).

PMID- 29186199
TI  - Genetic diversity and population structure of Prunus mira (Koehne) from the Tibet
      plateau in China and recommended conservation strategies.
AB  - Prunus mira Koehne, an important economic fruit crop with high breeding and
      medicinal values, and an ancestral species of many cultivated peach species, has
      recently been declared an endangered species. However, basic information about
      genetic diversity, population structure, and morphological variation is still
      limited for this species. In this study, we sampled 420 P. mira individuals from
      21 wild populations in the Tibet plateau to conduct a comprehensive analysis of
      genetic and morphological characteristics. The results of molecular analyses
      based on simple sequence repeat (SSR) markers indicated moderate genetic
      diversity and inbreeding (A = 3.8, Ae = 2.5, He = 0.52, Ho = 0.44, I = 0.95, FIS
      = 0.17) within P. mira populations. STRUCTURE, GENELAND, and phylogenetic
      analyses assigned the 21 populations to three genetic clusters that were
      moderately correlated with geographic altitudes, and this may have resulted from
      significantly different climatic and environmental factors at different
      altitudinal ranges. Significant isolation-by-distance was detected across the
      entire distribution of P. mira populations, but geographic altitude might have
      more significant effects on genetic structure than geographic distance in partial
      small-scale areas. Furthermore, clear genetic structure, high genetic
      differentiation, and restricted gene flow were detected between pairwise
      populations from different geographic groups, indicating that geographic barriers
      and genetic drift have significant effects on P. mira populations. Analyses of
      molecular variance based on the SSR markers indicated high variation (83.7% and
      81.7%), whereas morphological analyses revealed low variation (1.30%-36.17%)
      within the populations. Large and heavy fruits were better adapted than light
      fruits and nutlets to poor climate and environmental conditions at high
      altitudes. Based on the results of molecular and morphological analyses, we
      classified the area into three conservation units and proposed several
      conservation strategies for wild P. mira populations in the Tibet plateau.

PMID- 29186200
TI  - Sea-level rise and archaeological site destruction: An example from the
      southeastern United States using DINAA (Digital Index of North American
      Archaeology).
AB  - The impact of changing climate on terrestrial and underwater archaeological
      sites, historic buildings, and cultural landscapes can be examined through
      quantitatively-based analyses encompassing large data samples and broad
      geographic and temporal scales. The Digital Index of North American Archaeology
      (DINAA) is a multi-institutional collaboration that allows researchers online
      access to linked heritage data from multiple sources and data sets. The effects
      of sea-level rise and concomitant human population relocation is examined using a
      sample from nine states encompassing much of the Gulf and Atlantic coasts of the
      southeastern United States. A 1 m rise in sea-level will result in the loss of
      over >13,000 recorded historic and prehistoric archaeological sites, as well as
      over 1000 locations currently eligible for inclusion on the National Register of
      Historic Places (NRHP), encompassing archaeological sites, standing structures,
      and other cultural properties. These numbers increase substantially with each
      additional 1 m rise in sea level, with >32,000 archaeological sites and >2400
      NRHP properties lost should a 5 m rise occur. Many more unrecorded archaeological
      and historic sites will also be lost as large areas of the landscape are flooded.
      The displacement of millions of people due to rising seas will cause additional
      impacts where these populations resettle. Sea level rise will thus result in the
      loss of much of the record of human habitation of the coastal margin in the
      Southeast within the next one to two centuries, and the numbers indicate the
      magnitude of the impact on the archaeological record globally. Construction of
      large linked data sets is essential to developing procedures for sampling,
      triage, and mitigation of these impacts.

PMID- 29186201
TI  - Prognostic markers for survival in patients with oligodendroglial tumors; a
      single-institution review of 214 cases.
AB  - BACKGROUND: In the 2016 WHO classification, the diagnosis of oligodendroglioma
      has been restricted to IDH mutated, 1p19q codeleted tumors (IDHmut-codel). IDHmut
      oligoastrocytoma is now classified either as oligodendroglioma or astrocytoma
      based on presence of 1p19q codeletion. There is growing evidence that this
      molecular classification more closely reflects patient outcome. Due to the strong
      association between IDHmut-codel with oligodendroglial morphology, the additional
      impact of these markers on prognostic accuracy is largely unknown. Our aim was to
      assess the prognostic impact of IDHmut-codel in an unselected cohort of
      morphologically classified oligodendroglial tumors. METHODS: We performed a
      retrospective chart review of oligodendroglial tumors (WHO grade II and III)
      operated since 1983. A total of 214 tumors were included, and molecular
      information was available for 96 tumors. The prognostic impact of IDHmut-codel
      together with clinical parameters was analyzed by multivariate Cox regression.
      RESULTS: IDHmut-codel was registered in 64 tumors while for 150 tumors the
      molecular profile was negative for IDHmut-codel, unknown or incomplete.
      Comparison between the two groups showed that patients with IDHmut-codel tumors
      were younger (42 vs. 48 years), had more frequent frontal tumor location (48 vs.
      33%) and presented more often with seizures (72 vs. 51%) and no signs of
      neurological impairment (14 vs. 30%) than patients harboring tumors with unknown
      or incomplete molecular profile. Multivariate survival analysis identified young
      age (HR 1.78 >= 40 years), the absence of neurological deficits or personality
      changes (HR 0.57), frontal tumor location (HR 0.64) and the presence of IDHmut
      codel (HR 0.50) as independent predictors for longer survival, whereas tumor
      grade was not. CONCLUSION: In this unselected single-institution cohort, the
      presence of IDHmut-codel was associated with more beneficial clinical parameters
      and was identified as an independent prognostic factor. We conclude that the
      classical oligodendroglioma genotype provides additional prognostic data beyond
      clinical characteristics, morphology and tumor grade.

PMID- 29186202
TI  - Enhanced cell proliferation and osteogenic differentiation in electrospun
      PLGA/hydroxyapatite nanofibre scaffolds incorporated with graphene oxide.
AB  - One of the goals of bone tissue engineering is to mimic native ECM in
      architecture and function, creating scaffolds with excellent biocompatibility,
      osteoinductive ability and mechanical properties. The aim of this study was to
      fabricate nanofibrous matrices by electrospinning a blend of poly (L-lactic-co
      glycolic acid) (PLGA), hydroxyapatite (HA), and grapheme oxide (GO) as a
      favourable platform for bone tissue engineering. The morphology,
      biocompatibility, mechanical properties, and biological activity of all
      nanofibrous matrices were compared. The data indicate that the hydrophilicity and
      protein adsorption rate of the fabricated matrices were significantly increased
      by blending with a small amount of HA and GO. Furthermore, GO significantly
      boosted the tensile strength of the nanofibrous matrices, and the PLGA/GO/HA
      nanofibrous matrices can serve as mechanically stable scaffolds for cell growth.
      For further test in vitro, MC3T3-E1 cells were cultured on the PLGA/HA/GO
      nanofbrous matrices to observe various cellular activities and cell
      mineralization. The results indicated that the PLGA/GO/HA nanofibrous matrices
      significantly enhanced adhesion, and proliferation in MCET3-E1 cells and
      functionally promoted alkaline phosphatase (ALP) activity, the osteogenesis
      related gene expression and mineral deposition. Therefore, the PLGA/HA/GO
      composite nanofibres are excellent and versatile scaffolds for applications in
      bone tissue regeneration.

PMID- 29186204
TI  - Mocetinostat combined with gemcitabine for the treatment of leiomyosarcoma:
      Preclinical correlates.
AB  - Leiomyosarcoma (LMS) is a malignant soft tissue sarcoma (STS) with a dismal
      prognosis following metastatic disease. Chemotherapeutic intervention has
      demonstrated to have modest clinical efficacy with no curative potential in LMS
      patients. Previously, we demonstrated pan-HDAC inhibition to have a superior
      effect in various complex karyotypic sarcomas. In this study, our goal is to
      evaluate the therapeutic efficacy of mocetinostat alone and in combination with
      gemcitabine in LMS. Human leiomyosarcoma (LMS) cell lines were used for in vitro
      and in vivo studies. Compounds tested included the class I HDAC inhibitor,
      mocetinostat, and nucleoside analog, gemcitabine. MTS and clonogenic assays were
      used to evaluate the effect of mocetinostat on LMS cell growth. Cleaved caspase
      3/7 analysis was used to determine the effects of mocetinostat on apoptosis.
      Compusyn software was used to determine in vitro synergy studies for the
      combination of mocetinostat plus gemcitabine. A LMS xenograft model in SCID mice
      was used to test the impact of mocetinostat alone, gemcitabine alone and the
      combination of mocetinostat plus gemcitabine. Mocetinostat abrogated LMS cell
      growth and clonogenic potential, and enhanced apoptosis in LMS cell lines. The
      combination of mocetinostat plus gemcitabine exhibited a synergistic effect in
      LMS cells in vitro. Similarly, mocetinostat combined with gemcitabine resulted in
      superior anti-LMS effects in vivo. Mocetinostat reduced the expression of
      gemcitabine-resistance markers RRM1, RRM2, and increased the expression of
      gemcitabine-sensitivity marker, hENT1, in LMS cells. LMS are aggressive,
      metastatic tumors with poor prognosis where effective therapeutic interventions
      are wanting. Our studies demonstrate the potential utility of mocetinostat
      combined with gemcitabine for the treatment of LMS.

PMID- 29186205
TI  - Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.
AB  - Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons and is associated
      with multiple genetic and environmental factors. Although abnormalities in
      immunity are suggested to be involved in the etiology of narcolepsy, no decisive
      mechanism has been established. We previously reported chemokine (C-C motif)
      receptor 3 (CCR3) as a novel susceptibility gene for narcolepsy. To understand
      the role of CCR3 in the development of narcolepsy, we investigated sleep-wake
      patterns of Ccr3 knockout (KO) mice. Ccr3 KO mice exhibited fragmented sleep
      patterns in the light phase, whereas the overall sleep structure in the dark
      phase did not differ between Ccr3 KO mice and wild-type (WT) littermates.
      Intraperitoneal injection of lipopolysaccharide (LPS) promoted wakefulness and
      suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT
      mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark
      phase in both genotypes. After LPS administration, the proportion of time spent
      in wakefulness was higher, and the proportion of time spent in NREM sleep was
      lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes
      in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we
      quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt
      neurons in the lateral hypothalamus compared to WT mice. We found abnormalities
      in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3
      KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in
      narcolepsy patients.

PMID- 29186203
TI  - Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin
      deposition.
AB  - Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the
      cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase
      processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1
      results in precocious sister chromatid separation and cell aneuploidy, defects
      that arise through reduced levels of chromatin-bound cohesins which normally
      tether together sister chromatids (trans tethering). Mutation of Chl1 family
      members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities,
      consistent with a role for Chl1 in trans tethering which is required for
      efficient DNA repair. Chl1 promotes the recruitment of Scc2 to DNA which is
      required for cohesin deposition onto DNA. There is limited evidence, however,
      that Scc2 also directs the deposition onto DNA of condensins which promote
      tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to
      promote cis tethering and the role of both Chl1 and Scc2 to promote condensin
      recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant
      condensation defects both within the rDNA locus and genome-wide. Importantly,
      chl1 mutant cell condensation defects do not result from reduced chromatin
      binding of condensin, but instead through reduced chromatin binding of cohesin.
      We tested scc2-4 mutant cells and similarly found no evidence of reduced
      condensin recruitment to chromatin. Consistent with a role for Scc2 specifically
      in cohesin deposition, scc2-4 mutant cell condensation defects are irreversible.
      We thus term Chl1 a novel regulator of both chromatin condensation and sister
      chromatid cohesion through cohesin-based mechanisms. These results reveal an
      exciting interface between DNA structure and the highly conserved cohesin
      complex.

PMID- 29186206
TI  - Genetic signatures for Helicobacter pylori strains of West African origin.
AB  - Helicobacter pylori is a genetically diverse bacterial species that colonizes the
      stomach in about half of the human population. Most persons colonized by H.
      pylori remain asymptomatic, but the presence of this organism is a risk factor
      for gastric cancer. Multiple populations and subpopulations of H. pylori with
      distinct geographic distributions are recognized. Genetic differences among these
      populations might be a factor underlying geographic variation in gastric cancer
      incidence. Relatively little is known about the genomic features of African H.
      pylori strains compared to other populations of strains. In this study, we first
      analyzed the genomes of H. pylori strains from seven globally distributed
      populations or subpopulations and identified encoded proteins that exhibited the
      highest levels of sequence divergence. These included secreted proteins, an LPS
      glycosyltransferase, fucosyltransferases, proteins involved in molybdopterin
      biosynthesis, and Clp protease adaptor (ClpS). Among proteins encoded by the cag
      pathogenicity island, CagA and CagQ exhibited the highest levels of sequence
      diversity. We then identified proteins in strains of Western African origin
      (classified as hspWAfrica by MLST analysis) with sequences that were highly
      divergent compared to those in other populations of strains. These included ATP
      dependent Clp protease, ClpS, and proteins of unknown function. Three of the
      divergent proteins sequences identified in West African strains were
      characterized by distinct insertions or deletions up to 8 amino acids in length.
      These polymorphisms in rapidly evolving proteins represent robust genetic
      signatures for H. pylori strains of West African origin.

PMID- 29186207
TI  - Metabolic health assessment of zoo elephants: Management factors predicting
      leptin levels and the glucose-to-insulin ratio and their associations with health
      parameters.
AB  - Screening for metabolic-related health problems can enhance animal welfare, so
      the purpose of this study was to conduct the first metabolic health assessment of
      zoo elephants and use epidemiological methods to determine how factors in the
      captive environment were associated with metabolic hormone concentrations. In
      addition, we examined relationships between metabolic status and several fitness
      parameters: foot health, musculoskeletal health, reproductive cyclicity, and body
      condition. Two blood samples were collected 2 weeks apart from 87 Asian (Elephas
      maximus) and 105 African (Loxodonta africana) elephants managed by zoos
      accredited by the Association of Zoos and Aquariums for analysis of serum leptin,
      insulin, glucose and the glucose-to-insulin ratio (G:I). In females, mean (+/-
      SD) leptin concentrations and the G:I were lower (P<0.05) in Asian (3.93 +/- 2.21
      ng/ml and 110 +/- 86 units) compared to African (4.37 +/- 2.89 ng/ml and 208 +/-
      133 units) elephants, respectively. For males, mean leptin and the G:I were 4.99
      +/- 3.61 ng/ml and 253 +/- 181 units for Asian, and 3.72 +/- 2.00 ng/ml and 326
      +/- 231 units for African elephants, respectively, with no differences between
      species (P>0.05). As mean leptin concentration increased there was an increase in
      the odds of a female being non-cycling (P = 0.0083). The G:I was associated
      inversely with body condition (P = 0.0002); as the G:I increased there was a
      decreased risk of BCS = 4 or 5 as compared to the ideal, or BCS = 3. Neither
      leptin nor G:I were predictive of foot or musculoskeletal health scores. Factors
      related to walking and feeding practices were most influential in predicting
      metabolic status, whereas social and housing factors showed smaller, but
      significant effects. The metabolic health benefits of walking were detected if
      the time spent in staff-directed walking was 7 hours or more per week. The most
      protective feeding practices included implementing a random rather than
      predictable feeding schedule and limiting the number of methods presentation
      methods. Results indicate that leptin levels and G:I can be used as predictors of
      both ovarian cycle function and body condition, and are affected by zoo
      management in elephants.

PMID- 29186210
TI  - When Reducing Low-Value Care in Hospital Medicine Saves Money, Who Benefits ?
AB  - One emerging policy solution for deterring low-value care is to financially
      penalize physicians who prescribe it. However, physicians' willingness to support
      such policies may depend on whether they perceive that benefits accrue to
      patients or to insurers and hospitals. We surveyed physicians practicing hospital
      medicine to evaluate the association between policy support and physician beliefs
      about who benefits from the money saved through reducing low-value services in
      hospital medicine. Overall, physicians believed that more of any money saved
      would go to profits and leadership salaries for insurance companies and hospitals
      and/or health systems rather than to patients. These beliefs were associated with
      policy support: 66% of those supporting physician penalties were more likely to
      believe that benefits accrue to patients or physicians, compared to 39% of those
      not supporting policies (P < .001). Our findings are consistent with a sense of
      healthcare justice, in which physicians are less likely to support penalties
      imposed on themselves if the resulting benefits accrue to corporate or
      organizational interests. Effective physician penalties will likely need to
      address the belief that insurers and provider organizations stand to gain more
      than patients when low-value care services are reduced.

PMID- 29186209
TI  - Penalizing Physicians for Low-Value Care in Hospital Medicine: A Randomized
      Survey.
AB  - Low-value services-those for which there is little to no benefit, little benefit
      relative to cost, or outsized potential harm compared with benefit-persist widely
      despite professional consensus, guidelines, and national campaigns to reduce
      them. As policy makers consider financially penalizing physicians to deter low
      value services, physician support for such penalties remains unknown. We
      conducted a randomized survey experiment among physicians to evaluate how the
      framing of harms from low-value care-in terms of those to patients, healthcare
      institutions, or society-influenced physician support of financial penalties for
      low-value care services. Policy support rate was 39.6% overall and highest when
      the harms of low-value care were framed as costs to society (48.4%). Compared
      with respondents receiving the "patient harm" version, those receiving the
      "societal harm" version (adjusted odds ratio [OR] 2.83; 95% confidence interval
      [CI], 1.20-6.69), but not the "institutional harm" framing (adjusted OR 1.53; 95%
      CI, 0.66-3.53), were more likely to report policy support. Our results suggest
      that emphasizing the impact of these harms may increase acceptability of
      financial penalties among physicians and contribute to the larger effort to
      decrease low-value care in hospital settings.

PMID- 29186208
TI  - Cytotoxic effect of albumin coated copper nanoparticle on human breast cancer
      cells of MDA-MB 231.
AB  - PURPOSE: The aim of this study was to design a new nanocomposite that would have
      high cytotoxicity against invasive breast cancer cells and minimum side effects
      on normal cells. METHODS: An albumin nano-carrier for delivery of CuNPs was
      developed. The ACuNPs formation was characterized by TEM, DLS and UV-Vis,
      fluorescence and circular dichroism spectroscopy. The cytotoxic efficacy of the
      ACuNPs against human breast cancer cells (MDA-MB 231) and normal cells (MCF-10A)
      was compared using a standard MTT assay. The mechanism of cell death induced by
      ACuNPs was considered by inverted and fluorescent microscopy, flow cytometry and
      gel electrophoresis. The effects of compounds on ROS generations in MDA-MB 231
      cells were also studied. RESULTS: It was found that the resulted ACuNPs with a
      diameter of 62.7 nm and zeta potential of about -10.76 mV, are suitable for
      extravasation into tumor cells. In ACuNPs, the 90% of the secondary structure and
      almost all the tertiary structure of albumin remained intact. Comparing to CuNPs,
      ACuNPs could significantly suppress the viability of cancer cells while they were
      less toxic on normal cells. Compared with the untreated cells, the MDA-MB 231
      cell line showed higher levels of ROS production after treatment with ACuNPs. The
      increase in ROS production after 24 hours indicated that ACuNPs induce apoptosis.
      CONCLUSIONS: The ACuNPs characteristics such as intact structure of albumin, high
      toxicity against cancer cells comparing to normal cells and apoptosis induction
      as the mechanism of cell death, revealed that this nanocomposite is a good
      candidate to be used as a chemotherapeutic agent against invasive breast cancer
      cells.

PMID- 29186211
TI  - Hospital Administrators' Perspectives on Physician Engagement: A Qualitative
      Study.
AB  - BACKGROUND:  OBJECTIVE:  DESIGN, SETTING, PATIENTS:  INTERVENTION:  MEASUREMENTS:
      CONCLUSIONS: 

PMID- 29186212
TI  - Hospitalist Perspective of Interactions with Medicine Subspecialty Consult
      Services.
AB  - BACKGROUND: Medicine subspecialty consultation is becoming increasingly important
      in inpatient medicine. OBJECTIVE: We conducted a survey study in which we
      examined hospitalist practices and attitudes regarding medicine subspecialty
      consultation. DESIGN AND SETTING: The survey instrument was developed by the
      authors based on prior literature and administered online anonymously to
      hospitalists at 4 academic medical centers in the United States. MEASUREMENTS:
      The survey evaluated 4 domains: (1) current consultation practices, (2)
      preferences regarding consultation, (3) barriers to and facilitating factors of
      effective consultation, and (4) a comparison between hospitalist-fellow and
      hospitalist-subspecialty attending interactions. RESULTS: One hundred twenty-two
      of 261 hospitalists (46.7%) responded. The majority of hospitalists interacted
      with fellows during consultation. Of those, 90.9% reported that in-person
      communication occurred during less than half of consultations, and 64.4%
      perceived pushback at least "sometimes " in their consult interactions.
      Participants viewed consultation as an important learning experience, preferred
      direct communication with the consulting service, and were interested in more
      teaching during consultation. The survey identified a number of barriers to and
      facilitating factors of an effective hospitalist-consultant interaction, which
      impacted both hospitalist learning and patient care. Hospitalists reported more
      positive experiences when interacting with subspecialty attendings compared to
      fellows with regard to multiple aspects of the consultation. CONCLUSION: The
      hospitalist-consultant interaction is viewed as important for both hospitalist
      learning and patient care. Multiple barriers and facilitating factors impact the
      interaction, many of which are amenable to intervention.

PMID- 29186213
TI  - Returns to Emergency Department, Observation, or Inpatient Care Within 30 Days
      After Hospitalization in 4 States, 2009 and 2010 Versus 2013 and 2014.
AB  - BACKGROUND: Nationally, readmissions have declined for acute myocardial
      infarction (AMI) and heart failure (HF) and risen slightly for pneumonia, but
      less is known about returns to the hospital for observation stays and emergency
      department (ED) visits. OBJECTIVE: To describe trends in rates of 30-day, all
      cause, unplanned returns to the hospital, including returns for observation stays
      and ED visits. DESIGN: By using Healthcare Cost and Utilization Project data, we
      compared 210,007 index hospitalizations in 2009 and 2010 with 212,833 matched
      hospitalizations in 2013 and 2014. SETTING: Two hundred and one hospitals in
      Georgia, Nebraska, South Carolina, and Tennessee. PATIENTS: Adults with private
      insurance, Medicaid, or no insurance and seniors with Medicare who were
      hospitalized for AMI, HF, and pneumonia. MEASUREMENTS: Thirty-day hospital return
      rates for inpatient, observation, and ED visits. RESULTS: Return rates remained
      stable among adults with private insurance (15.1% vs 15.3%; P = 0.45) and
      declined modestly among seniors with Medicare (25.3% vs 25.0%; P = 0.04).
      Increases in observation and ED visits coincided with declines in readmissions
      (8.9% vs 8.2% for private insurance and 18.3% vs 16.9% for Medicare, both P <=
      0.001). Return rates rose among patients with Medicaid (31.0% vs 32.1%; P = 0.04)
      and the uninsured (18.8% vs 20.1%; P = 0.004). Readmissions remained stable
      (18.7% for Medicaid and 9.5% for uninsured patients, both P > 0.75) while
      observation and ED visits increased. CONCLUSIONS: Total returns to the hospital
      are stable or rising, likely because of growth in observation and ED visits.
      Hospitalists' efforts to improve the quality and value of hospital care should
      consider observation and ED care.

PMID- 29186214
TI  - Things We Do For No Reason: Electrolyte Testing in Pediatric Acute
      Gastroenteritis.

PMID- 29186215
TI  - Revisiting monosaccharide analysis - quantitation of a comprehensive set of
      monosaccharides using dynamic multiple reaction monitoring.
AB  - A rapid method for the quantitation of sixteen neutral and acidic
      monosaccharides, from both animal and plant sources was developed using ultra
      high performance liquid chromatography triple quadrupole mass spectrometry
      (UHPLC/QqQ-MS) in dynamic multiple reaction monitoring (dMRM) mode.
      Monosaccharides including three pentoses (ribose, xylose, arabinose), two
      deoxyhexoses (rhamnose, fucose), five hexoses (fructose, mannose, allose,
      glucose, galactose), two hexuronic acids (glucuronic acid, galacturonic acid),
      and two N-acetyl-hexosamines (GlcNAc, GalNAc), were derivatized with 1-phenyl-3
      methyl-5-pyrazolone (PMP), while underivatized sialic acids, Neu5Ac and Neu5Gc,
      were simultaneously analyzed with a 10-minute run. With the optimized UHPLC
      conditions, baseline separations of the isomers were achieved. The sensitivity
      and calibration ranges of this method were determined. The limits of detection
      were between femtomoles and attomoles with linear ranges spanning four to six
      orders of magnitude and coefficients of variation (CVs) <=7.2%. Spiking
      experiments performed on a pooled fecal sample demonstrated the high accuracy of
      this method even when applied to samples with complicated matrices. The validated
      method was applied to fecal samples from an infant transitioning from breast milk
      to weaning foods. Major milk monosaccharides including galactose, fucose,
      glucose, GlcNAc, and Neu5Ac were found to be the most abundant components in the
      feces of milk-fed infants. PMP-derivatives of nine other monosaccharides
      including apiose, lyxose, altrose, talose, gulose, glucosamine, galactosamine,
      mannosamine, and N-acetylmannosamine (ManNAc) were also tested and could be added
      to the quantitation method depending on the need. The speed and sensitivity of
      the method makes it readily adaptable to rapid throughput analysis of
      monosaccharides in biological samples.

PMID- 29186217
TI  - The role of symmetry breaking in the structural trapping of light-induced excited
      spin states.
AB  - Light-Induced Excited Spin State Trapping (LIESST) data are reported for seven
      isostructural solvate salts from the iron(ii)/2,6-di(pyrazol-1-yl)pyridine
      family. A complicated relationship between their spin-crossover T1/2 and
      T(LIESST) values may reflect low-temperature thermal and light-induced symmetry
      breaking, which is shown by one of the compounds but not by two others.

PMID- 29186216
TI  - Investigating d-lysine stereochemistry for epigenetic methylation, demethylation
      and recognition.
AB  - Histone lysine methylation is regulated by Nepsilon-methyltransferases,
      demethylases, and Nepsilon-methyl lysine binding proteins. Thermodynamic,
      catalytic and computational studies were carried out to investigate the
      interaction of three epigenetic protein classes with synthetic histone substrates
      containing l- and d-lysine residues. The results reveal that out of the three
      classes, Nepsilon-methyl lysine binding proteins are superior in accepting
      lysines with the d-configuration.

PMID- 29186218
TI  - Post-targeting strategy for ready-to-use targeted nanodelivery post cargo
      loading.
AB  - Based on boronate formation, this study reports a post-targeting methodology
      capable of readily installing versatile targeting modules onto a cargo-loaded
      nanoplatform in aqueous mediums. This permits the targeted nanodelivery of broad
      spectrum therapeutics (drug/gene) in a ready-to-use manner while overcoming the
      PEGylation-dilemma that frequently occurs in conventional targeting approaches.

PMID- 29186219
TI  - Fullerenes - how 25 years of charge transfer chemistry have shaped our
      understanding of (interfacial) interactions.
AB  - In this review article, we highlight over 25 years of fullerene research in
      charge transfer chemistry. The major thrust of this work is to illustrate
      interfacial interactions between fullerenes and porphyrins in electron donor
      acceptor conjugates as well as self-assembled associates and co-crystallites all
      the way to organic photovoltaics. Hereby, the analysis of the fundamental
      proceses, namely, energy transfer, charge shift, charge separation as well as
      charge recombination stand at the forefront. Our examples, illustrate on how fine
      tuning the structure leads to substantial alteration of interfacial interactions.

PMID- 29186220
TI  - Self-assembly of water-soluble silver nanoclusters: superstructure formation and
      morphological evolution.
AB  - Supramolecular self-assembly, based on non-covalent interactions, has been
      employed as an efficient approach to obtain various functional materials from
      nanometer-sized building blocks, in particular, [Ag6(mna)6]6-, mna =
      mercaptonicotinate (Ag6-NC). A challenging issue is how to modulate the self
      assembly process through regulating the relationship between building blocks and
      solvents. Herein, we report the controlled self-assembly of hexanuclear silver
      nanoclusters into robust multilayer vesicles in different solvents, DMSO, CH3CN,
      EG and MeOH. Their unique luminescence enables them to be bifunctional probes to
      sense Fe3+ and dl-dithiothreitol (DTT). By protonating the Ag6-NC to Ag6-H-NC
      using hydrochloric acid (HCl), the multilayer vesicles survive in aprotic
      solvents, DMSO and CH3CN, but are transformed to nanowires in protic solvents,
      water, EG and MeOH. Our results demonstrated that the solvent-bridged H-bond
      plays a key role in the evolution of the morphologies from vesicles to nanowires.
      Moreover, the nanowires could further hierarchically self-assemble in water into
      hydrogels with high water content (99.5%), and with remarkable mechanical
      strength and self-healing properties. This study introduces a robust cluster
      based building block in a supramolecular self-assembly system and reveals the
      significance of aprotic and protic solvents for the modulation of the
      morphologies of cluster-based aggregates.

PMID- 29186223
TI  - Stability and spectral properties of the dication Ne.
AB  - The dication Ne and its stability properties are studied by ab initio methods.
      Assuming the Born-Oppenheimer approximation and employing multireference
      configuration interaction techniques, potential energy curves of its low-lying
      electronic spectrum have been computed and analyzed. In addition to identifying
      metastable electronic and vibrational states, possible electronic transitions and
      decay mechanisms are examined. Our results also shed new light on the role of the
      dication as an excimer system and the interpretation of experimentally observed
      continua in Ne2 ultraviolet emission spectra.

PMID- 29186221
TI  - Electrochemistry: general discussion.

PMID- 29186222
TI  - High-frequency irreversible electroporation targets resilient tumor-initiating
      cells in ovarian cancer.
AB  - We explored the use of irreversible electroporation (IRE) and high-frequency
      irreversible electroporation (H-FIRE) to induce cell death of tumor-initiating
      cells using a mouse ovarian surface epithelial (MOSE) cancer model. Tumor
      initiating cells (TICs) can be successfully destroyed using pulsed electric field
      parameters common to irreversible electroporation protocols. Additionally, high
      frequency pulses seem to induce cell death of TICs at significantly lower
      electric fields suggesting H-FIRE can be used to selectively target TICs and
      malignant late-stage cells while sparing the non-malignant cells in the
      surrounding tissue. We evaluate the relationship between threshold for cell death
      from H-FIRE pulses and the capacitance of cells as well as other properties that
      may play a role on the differences in the response to conventional IRE versus H
      FIRE treatment protocols.

PMID- 29186224
TI  - Controlling Ag-doping in [AgxAu25-x(SC6H11)18]- nanoclusters: cryogenic optical,
      electronic and electrocatalytic properties.
AB  - Doping metal nanoclusters with a second type of metal is a powerful method for
      tuning the physicochemical properties of nanoclusters at the atomic level and it
      also provides opportunities for a fundamental understanding of alloying rules as
      well as new applications. Herein, we have devised a new, one-phase strategy for
      achieving heavy Ag-doping in Au25(SR)18 nanoclusters. This strategy overcomes the
      light doping of silver by previous methods. X-ray crystallography together with
      ESI-MS determined the composition of the product to be [AgxAu25-x(SC6H11)18]-
      with x ~ 21. Cryogenic optical spectroscopy (80-300 K) revealed fine features in
      optical absorption peaks. Interestingly, the heavy doping of silver does not
      significantly change the electron-phonon coupling strength and the surface phonon
      frequency. DFT simulations reproduced the experimentally observed trend of
      electronic structure evolution with Ag doping. We further investigated the
      electrocatalytic performance of such heavily Ag-doped nanoclusters for oxygen
      reduction in alkaline solutions. The mass activity of ligand-off [AgxAu25
      x(SC6H11)18]- nanoclusters (217.4 A g-1metal) was determined to be higher than
      that of ligand-on nanoclusters (29.6 A g-1metal) at a potential of -0.3 V (vs.
      Ag/AgCl). The rotating disk electrode (RDE) studies revealed the tunable kinetic
      features of the nanoclusters by ligand removal.

PMID- 29186225
TI  - Enhanced broadband photoresponse of a self-powered photodetector based on
      vertically grown SnS layers via the pyro-phototronic effect.
AB  - Here, we demonstrate the broadband photoresponse from ultraviolet (365 nm) to
      near-infrared (850 nm) wavelengths from a photodetector based on vertically grown
      SnS layers. Particularly, the photoinduced current density of the device
      increased from 100 to 470 MUA cm-2 with a wavelength of 760 nm and an intensity
      of 7 mW cm-2 by utilizing the pyro-phototronic potential. In addition, the
      photodetector demonstrated ultrafast response rates of ~12 MUs for the rise and
      ~55 MUs for the decay times over the studied range. Moreover, a good
      photoresponsivity of 13 mA W-1 and a high photodetectivity of 3 * 1014 Jones at a
      wavelength of 760 nm with an intensity of 7 mW cm-2 were measured, representing
      enhancements of 340% and 3960%, respectively, with the pyroelectric potential.
      This excellent broadband performance was attributed to the photon-induced
      pyroelectric effect in the vertically grown SnS layers, which also modulated the
      optoelectronic processes. This novel approach will open a new avenue to design a
      broadband ultrafast device for advanced optoelectronics.

PMID- 29186226
TI  - Organic semiconductor crystals.
AB  - Organic semiconductors have attracted a lot of attention since the discovery of
      highly doped conductive polymers, due to the potential application in field
      effect transistors (OFETs), light-emitting diodes (OLEDs) and photovoltaic cells
      (OPVs). Single crystals of organic semiconductors are particularly intriguing
      because they are free of grain boundaries and have long-range periodic order as
      well as minimal traps and defects. Hence, organic semiconductor crystals provide
      a powerful tool for revealing the intrinsic properties, examining the structure
      property relationships, demonstrating the important factors for high performance
      devices and uncovering fundamental physics in organic semiconductors. This review
      provides a comprehensive overview of the molecular packing, morphology and charge
      transport features of organic semiconductor crystals, the control of
      crystallization for achieving high quality crystals and the device physics in the
      three main applications. We hope that this comprehensive summary can give a clear
      picture of the state-of-art status and guide future work in this area.

PMID- 29186227
TI  - "Snorkelling" vs. "diving" in mixed micelles probed by means of a molecular
      bathymeter.
AB  - A photoactive bathymeter based on a carboxylic acid moiety covalently linked to a
      signalling methoxynaphthalene (MNP) fluorophore has been designed to prove the
      concept of "snorkelling" vs. "diving" in mixed micelles (MM). The carboxylic acid
      "floats" on the MM surface, while the MNP unit sinks deep in MM. The rate
      constants of MNP fluorescence quenching by iodide, which remains basically in
      water, consistently decrease with increasing spacer length, revealing different
      regions. This is associated with the distance MNP should "dive" in MM to achieve
      protection from aqueous reactants. Unequivocal proof of the exergonic
      photoinduced electron transfer was obtained from the UV-visible spectral
      signature of I3- upon steady-state photolysis. The applicability of the
      bathymeter was examined upon testing a family of MNP derivatives. The obtained
      results were validated by comparison with different lipophilicity tests: (i) a
      modified version of the Kow partition coefficient and (ii) the retention factor
      on thin layer chromatography. This concept could potentially be extended to test
      drugs or pharmacophores exhibiting any photoactive moiety.

PMID- 29186228
TI  - Tungsten-coated nano-boron carbide as a non-noble metal bifunctional
      electrocatalyst for oxygen evolution and hydrogen evolution reactions in alkaline
      media.
AB  - Herein, tungsten-coated nano-boron carbide (W-WB4-WCx/B4C) particles were
      prepared by heating a mixture of B4C and W powder using a spark plasma coating
      (SPC) method. During the discharge treatment process, metal W in the mixture is
      activated and reacts with B4C to form WCx, WB4, and graphite nanoribbons. The
      oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) performance
      of W-WB4-WCx/B4C is tested in an alkaline solution, and the results show that the
      W-WB4-WCx/B4C composite electrocatalyst exhibits a low overpotential of 0.36 V at
      10 mA cm-2 for the OER, a small overpotential of -0.19 V (j = 10 mA cm-2) for the
      HER, as well as good stability. The significantly enhanced electrocatalytic
      performance of the W-WB4-WCx/B4C composites is attributed to their unique
      structure, in which WCx and WB4 not only improve the catalytic activity for the
      OER and HER, but also effectively anchor the W coating on the substrate.

PMID- 29186230
TI  - Probing halogen-halogen interactions in solution.
AB  - Halogen-halogen interactions are a particularly interesting class of halogen
      bonds that are known to be essential design elements in crystal engineering. In
      solution, it is likely that halogen-halogen interactions also play a role, but
      the weakness of this interaction makes it difficult to characterize or even
      simply detect. We have designed a supramolecular balance that allows detecting
      BrBr interactions between CBr3 groups in solution and close to room temperature.
      The sensitivity and versatility of the chosen platform have allowed accumulating
      consistent data. In halogenoalkane solvents, we propose estimates for the free
      energy of these weak halogen bond interactions. In toluene solutions, we show
      that the interactions between Br atoms and the solvent aromatic groups dominate
      over the BrBr interactions.

PMID- 29186231
TI  - Excited state energy fluctuations in the Fenna-Matthews-Olson complex from
      molecular dynamics simulations with interpolated chromophore potentials.
AB  - We analyze the environment-induced fluctuation of pigment excitation energies in
      the Fenna-Matthews-Olson (FMO) complex from various perspectives, by employing an
      interpolation-based all-atom potential energy model for describing realistic
      pigment vibrations. We conduct molecular dynamics simulations on a 100 ns
      timescale, which is an extent that can enclose the effect of static disorder, and
      demonstrate its timescale separation from fast dynamic disorder. We extract the
      spectral densities of the complex by considering both the site and the exciton
      bases. We show that exciton delocalization reduces the effective environmental
      fluctuation and rationalize this aspect based on a model of fluctuating molecular
      aggregates. We also obtained the spectral density of the lowest exciton state
      under low temperature conditions and show that it reasonably well reproduces the
      experimental result. Finally, by additionally performing non-equilibrium excited
      state trajectory simulations, we show that the system lies well within the linear
      response regime after photo-absorption and that the pigments do not visit
      anharmonic regions of the potential surface to a significant extent. This
      indicates that methodologies based on harmonic bath models are indeed reasonable
      approaches for describing the excited state dynamics of the FMO complex.

PMID- 29186229
TI  - HyRes: a coarse-grained model for multi-scale enhanced sampling of disordered
      protein conformations.
AB  - Efficient coarse-grained (CG) models can be coupled with atomistic force fields
      to accelerate the sampling of atomistic energy landscapes in the multi-scale
      enhanced sampling (MSES) framework. This approach may be particularly suitable
      for generating atomistic conformational ensembles of intrinsically disordered
      proteins (IDPs). While MSES is relatively robust to inherent CG artifacts,
      achieving optimal sampling efficiency requires CG modeling to generate the local
      and long-range fluctuations that are largely consistent with those at the
      atomistic level. Here, we describe a new hybrid resolution CG model (HyRes) for
      MSES simulations of disordered protein states, which is specifically designed to
      provide semi-quantitative secondary structure propensities together with a
      qualitative description of long-range nonspecific interactions. The HyRes model
      contains an atomistic description of the backbone with intermediate resolution
      side chains. The secondary structure propensities are tuned by adjusting the
      backbone hydrogen-bonding strength and the phi/psi torsion profile. The sizes and
      covalent geometries of the side chains are parameterized to reproduce
      distributions derived from atomistic simulations. Lennard-Jones parameters for
      sidechain beads are assigned to reproduce statistical potentials derived from the
      protein structural database, and then globally parameterized with nonspecific
      electrostatic interactions to reproduce the free energy profiles of pair wise
      interactions and the key conformational properties of model peptides. Application
      of HyRes to MSES simulations of small IDPs suggests that it is capable of driving
      faster structural transitions at the atomistic level and increasing the
      convergence rate compared to the Calpha-only Go-like models previously utilized.
      With further optimization, we believe that the new CG model could greatly improve
      the efficiency of MSES simulations of the larger and more complex IDPs frequently
      involved in cellular signalling and regulation.

PMID- 29186232
TI  - Why do the Togni reagent and some of its derivatives exist in the high-energy
      hypervalent iodine form? New insight into the origins of their kinetic stability.
AB  - In a recent study published in ChemComm, H. F. Schaefer and coworkers showed that
      the Togni trifluoromethyltation reagent and some of its derivatives appear in a
      high-energy hypervalent form. The (kinetic) stability of these reagents is
      granted by the five-membered ring of their benziodoxole-based scaffold, which
      prevents isomerization to the (inactive) acyclic ether form. Whereas the
      thermodynamic stability of these reagents can be predicted on the basis of the
      trans influence of the electrophilic substituent, no such descriptor was found
      for their kinetic stability. In this study, we explore an array of Togni-type
      reagents, and show that the barrier to isomerization can be predicted based on
      the bond length between the iodine atom and the electrophilic substituent. For
      compounds, where this correlation does not hold, we have a reliable indication
      that the structure of the transition state is at variance with those in the
      series.

PMID- 29186233
TI  - A new strategy to address the challenges of nanoparticles in practical water
      treatment: mesoporous nanocomposite beads via flash freezing.
AB  - Various engineering nanoparticles (NPs) exhibit high reactivity and great
      potential for water decontamination. Encapsulation of NPs into millimeter-sized
      polymer hosts is a very promising strategy to address their inherent bottlenecks
      for scale-up water treatment such as aggregation, difficult operation and
      potential risks when released into water. However, the inevitable host pore
      blockage accompanying NP loadings significantly compromise their decontamination
      reactivity. Herein, a newly developed flash freezing method was utilized to embed
      alpha-Fe2O3 NPs (3 nm, 7 nm and 18 * 90 nm) inside millimetric polystyrene to
      prepare mesoporous nanocomposites Fe2O3@PS. All the as-obtained Fe2O3@PS
      nanocomposites feature high mesoporosity, well-dispersed NPs and highly
      accessible sites. The amount of Fe-OH species, i.e., the active sites for As(v)
      sequestration, of the embedded 3 nm-Fe2O3 is dramatically increased 3.6 times
      over the bare NPs, resulting in higher adsorption capacity and affinity. The 3 nm
      Fe2O3@PS is capable of producing clean water 2000-fold greater in mass
      successively in column adsorption, with As(v) reducing from 176 MUg L-1 initially
      to <1 MUg L-1. Also, Fe2O3@PS can be readily regenerated for cyclic use with
      negligible NPs leaking into water. This study provides an elaborate strategy to
      address the trade-off between easy operation and decontamination reactivity of
      NPs for water treatment.

PMID- 29186234
TI  - Kinetics of the simplest Criegee intermediate reaction with ozone studied using a
      mid-infrared quantum cascade laser spectrometer.
AB  - The kinetics of the reaction of CH2OO with ozone has been studied by monitoring
      CH2OO using time-resolved infrared (IR) absorption spectroscopy, which utilized
      the fast chirped IR pulse train from a quantum cascade laser [J. Chem. Phys.,
      2017, 146, 244302]. CH2OO was prepared by photolyzing a gas mixture of
      CH2I2/O2/O3 at 352 nm; the photolysis wavelength was chosen to minimize the
      photodissociation of O3. The measured rate coefficient at 298 K and 30 Torr is
      (6.7 +/- 0.5) * 10-14 cm3 s-1, independent of pressure from 30 to 100 Torr. The
      result indicates that previous ab initio calculations either underestimated or
      overestimated this reaction rate by one order of magnitude or more. The result
      also implies that, the reaction of the Criegee intermediate with ozone may play a
      role in laboratory studies of ozonolysis of alkenes. However, this reaction would
      not compete with other CH2OO sinks in the atmosphere.

PMID- 29186235
TI  - Coating ZnO nanoparticle films with DNA nanolayers for enhancing the electron
      extracting properties and performance of polymer solar cells.
AB  - Here we present for the first time polymer solar cells that incorporate
      biological material that show state of the art efficiencies in excess of 8%. The
      performance of inverted polymer solar cells was improved significantly after
      deposition of ZnO nanoparticles (ZnO-NPs) together with a thin deoxyribonucleic
      acid nanolayer and used as an electron extraction layer (EEL). The ZnO-NPs/DNA
      double layer improved the rectifying ratio, shunt resistance of the cells as well
      as lowering the work function of the electron-collecting contact. Importantly,
      the ZnO-NPs/DNA bilayer enhanced the power conversion efficiency of cells
      considerably compared to cells with EELs made of only DNA (improvement of 56% in
      relative terms) or only ZnO-NPs (improvement of 19% in relative terms) reaching a
      best power conversion efficiency of 8.5%. The ZnO-NPs/DNA double layer cells also
      outperformed ones made with one of the most efficient previous synthetic
      composite EELs (i.e. ZnO/PEIE(poly(ethyleneimine)-ethoxylated)). Since all
      fabrication procedures were carried out at low (<150  degrees C) or room
      temperature, we have applied the findings to flexible substrates as well as on
      glass obtaining a high PCE of 7.2%. The solar cells with the biological/metal
      oxide composite EELs also delivered an improvement in the stability (~20% in
      relative term) compared to that with ZnO-NPs only. All these findings show that
      natural materials, in this case DNA, the premium biological material, can be
      incorporated in organic semiconductor devices in tandem with inorganic devices
      delivering uncompromising levels of performance as well as significant
      improvements.

PMID- 29186236
TI  - Quasi physisorptive two dimensional tungsten oxide nanosheets with extraordinary
      sensitivity and selectivity to NO2.
AB  - Attributing to their distinct thickness and surface dependent physicochemical
      properties, two dimensional (2D) nanostructures have become an area of increasing
      interest for interfacial interactions. Effectively, properties such as high
      surface-to-volume ratio, modulated surface activities and increased control of
      oxygen vacancies make these types of materials particularly suitable for gas
      sensing applications. This work reports a facile wet-chemical synthesis of 2D
      tungsten oxide nanosheets by sonication of tungsten particles in an acidic
      environment and thermal annealing thereafter. The resultant product of large
      nanosheets with intrinsic substoichiometric properties is shown to be highly
      sensitive and selective to nitrogen dioxide (NO2) gas, which is a major
      pollutant. The strong synergy between polar NO2 molecules and tungsten oxide
      surface and also abundance of active surface sites on the nanosheets for molecule
      interactions contribute to the exceptionally sensitive and selective response. An
      extraordinary response factor of ~30 is demonstrated to ultralow 40 parts per
      billion (ppb) NO2 at a relatively low operating temperature of 150  degrees C,
      within the physisorption temperature band for tungsten oxide. Selectivity to NO2
      is demonstrated and the theory behind it is discussed. The structural,
      morphological and compositional characteristics of the synthesised and annealed
      materials are extensively characterised and electronic band structures are
      proposed. The demonstrated 2D tungsten oxide based sensing device holds the
      greatest promise for producing future commercial low-cost, sensitive and
      selective NO2 gas sensors.

PMID- 29186237
TI  - A redox-responsive mesoporous silica based nanoplatform for in vitro tumor
      specific fluorescence imaging and enhanced photodynamic therapy.
AB  - In order to obtain an optimal therapeutic effect with minimal systemic toxicity,
      a redox-responsive mesoporous silica nanoparticle (MSN)-based platform modified
      with protoporphyrin IX (PpIX)-multifunctional peptides was synthesized as an
      intelligent theranostic agent carrier. This redox-responsive nanoplatform could
      release the theranostic agent under a glutathione stimulus, produce fluorescence
      recovery for tumor-specific fluorescence imaging and provide tumor-enhanced
      photodynamic therapy.

PMID- 29186238
TI  - Electrochemical aspects of photocatalysis: Au@FeS2 nanocomposite for removal of
      industrial pollutant.
AB  - A wide range of endeavors have been dedicated to building up an impetus in the
      field of catalysis to enhance the removal of toxic contaminants from water. This
      study characterizes an efficient photocatalyst for water treatment technique.
      Herein, the synthesis of a photocatalyst Au@FeS2 for the degradation of textile
      dye NOVACRON Red Huntsman (NRH) has been demonstrated. Photocatalysis under
      visible light with varying concentrations of catalyst have been explored along
      with the degradation kinetics to determine the synergistic impact on degradation
      technique. The Au@FeS2 exhibits excellent photocatalytic activity and good
      reusability under visible light irradiation. The efficiency of Au@FeS2 (1 g L-1)
      in the degradation of the textile dye NRH (1 mg L-1) is found to be 96.02% in
      just 60 minutes, which is considerably higher than that of FeS2 (1 g L-1) (95.63%
      in 120 minutes). The electrochemical performance also supports the enhanced
      photocatalytic activity of Au@FeS2. The photocatalytic and electrochemical
      activity of Au@FeS2 offers an innovative platform for environmental remediation
      applications.

PMID- 29186239
TI  - Cutaneous mucormycosis.
AB  - Cutaneous mucormycosis is an emerging fungal infection caused by opportunistic
      fungi of the phylum Glomeromycota. It is frequent in poorly controlled diabetic
      patients and individuals with immunosuppression. It is usually acquired by direct
      inoculation through trauma. The clinical presentation is nonspecific, but an
      indurated plaque that rapidly evolves to necrosis is a common finding. Diagnosis
      should be confirmed by demonstration of the etiological agent and new molecular
      diagnostic tools have recently been described. It is an invasive life-threatening
      disease and in order to improve survival, a prompt diagnosis and
      multidisciplinary management should be provided. The treatment of choice is
      amphotericin B, but new azoles, such as posaconazole and isavuconazole, must be
      considered.

PMID- 29186240
TI  - Evaluation of treatment response to autologous transplantation of noncultured
      melanocyte/keratinocyte cell suspension in patients with stable vitiligo.
AB  - BACKGROUND: Vitiligo is a chronic disease characterized by the appearance of
      achromic macules caused by melanocyte destruction. Surgical treatments with
      melanocyte transplantation can be used for stable vitiligo cases. OBJECTIVES: To
      evaluate treatment response to the autologous transplantation of noncultured
      epidermal cell suspension in patients with stable vitiligo. METHODS: Case series
      study in patients with stable vitiligo submitted to noncultured epidermal cell
      suspension transplantation and evaluated at least once, between 3 and 6 months
      after the procedure, to observe repigmentation and possible adverse effects. The
      maximum follow-up period for some patients was 24 months. RESULTS: Of the 20
      patients who underwent 24 procedures, 25% showed an excellent rate of
      repigmentation, 50% good repigmentation, 15% regular, and 10% poor response. The
      best results were observed in face and neck lesions, while the worst in extremity
      lesions (88% and 33% of satisfactory responses, respectively). Patients with
      segmental vitiligo had a better response (84%) compared to non-segmental ones
      (63%). As side effects were observed hyperpigmentation of the treated area and
      the appearance of Koebner phenomenon in the donor area. STUDY LIMITATIONS: Some
      limitations of the study included the small number of patients, a subjective
      evaluation, and the lack of long-term follow-up on the results. CONCLUSION:
      Noncultured epidermal cell suspension transplantation is efficient and well
      tolerated for stable vitiligo treatment, especially for segmental vitiligo on the
      face and neck.

PMID- 29186241
TI  - Clinical features of von Zumbusch type of generalized pustular psoriasis in
      children: a retrospective study of 26 patients in southwestern China.
AB  - BACKGROUND: Von Zumbusch type of generalized pustular psoriasis is a rare variant
      of psoriasis in children. It can occur in patients with or without psoriasis
      vulgaris. OBJECTIVE: The aim of the study was to discuss the precipitating
      factors, clinical manifestations, laboratory data and therapy of von Zumbusch
      type of generalized pustular psoriasis in children from southwestern China and to
      improve the diagnosis and treatment level. METHODS: A retrospective analysis was
      conducted for inpatients aged 14 years old or less with von Zumbusch type of
      generalized pustular psoriasis in our department from 2005 to 2014. RESULTS: A
      total of 26 patients were included, of whom four (15.38%) had previous history of
      psoriasis vulgaris and one (3.85%) had previous history of psoriasis
      arthropathica. Mean onset age was 6.90 years. Gender distribution was equivalent.
      Incidence of the disease in summer and autumn was higher than that in winter and
      spring. Nineteen (73.08%) cases were triggered by infection, two (7.69%) cases
      were caused by sudden discontinuation of systemic use of corticosteroid. Twenty
      four (92.31%) cases had concomitant fever. The initial lesion manifested as non
      follicular sterile pustules on erythema. Sixteen patients responded well to
      acitretin, 11 to Tripterygium wilfordii Hook F (TwHF), two to cyclosporine, and
      one to methotrexate. STUDY LIMITATIONS: This study is a retrospective one and the
      number of cases is small. CONCLUSION: Von Zumbusch type of generalized pustular
      psoriasis is a rare disease in children, infection is the most common
      precipitating factor, acitretin is the first-line therapy, traditional Chinese
      medicine TwHF also can be used.

PMID- 29186242
TI  - Study of serum levels and skin expression of S100B protein in psoriasis.
AB  - BACKGROUND: S100B protein was reported to be elevated in psoriatic patients'
      serum, with no previous evaluation of its skin expression, in contrast to the
      extensively studied S100 protein. OBJECTIVE: To evaluate the serum level and skin
      expression of S100B in psoriasis to assess its possible involvement in its
      pathogenesis. METHODS: Serum level of S100B protein was estimated in 40 psoriatic
      patients of different clinical varieties and 10 healthy controls. S100B protein
      expression was assessed immunohistochemically in lesional and non-lesional skin
      of patients and in normal skin of controls. Relation to disease severity was also
      evaluated. RESULTS: Serum level of S100B protein was significantly higher in
      psoriatic patients (0.15+/-0.03 ug/l) than in controls (0.03+/-0.007 ug/l) (P
      value <0.001) with no significant correlation with PASI score. On comparing
      grades of S100B protein skin expression in lesional and non-lesional skin
      biopsies, a statistically significant difference was found (P=0.046) with higher
      percentage of strong S100B skin expression (60%) in non-lesional than in lesional
      (42%) skin. All the control biopsies showed negative expression. STUDY
      LIMITATIONS: Relatively small sample size with a limited range of low PASI
      scores. CONCLUSION: This study points to a potential link between psoriasis and
      S100B protein with higher serum and skin expression in patients than in controls.

PMID- 29186243
TI  - Familial progressive hyper- and hypopigmentation: a report on a Chinese family
      and evidence for genetic heterogeneity.
AB  - BACKGROUND: Familial progressive hyper- and hypopigmentation (FPHH) is a rare
      genodermatosis that is characterized by diffuse hyper- and hypopigmented spots on
      the skin and mucous membranes. It is caused by a pathogenic mutation of the KITLG
      gene. OBJECTIVES: To investigate the clinical features and mutation of the KITLG
      gene in a Chinese family with FPHH. METHODS: Histopathological and
      immunohistochemical analysis of lesions from the proband was performed. The KITLG
      gene was screened for the presence of mutations. RESULTS: A Chinese family
      containing 14 individuals with FPHH was described, and the proband was a 5-year
      old girl showing diffuse hyper- and hypopigmented lesions on her extremities and
      trunk. Histopathological and immunohistochemical staining for S100 and HMB45 of
      skin biopsy specimens from the hyperpigmented areas showed a striking increase in
      melanin throughout the epidermis, especially in the basal cell layer, and
      staining of hypopigmented area specimens displayed lower levels of melanin in the
      epidermis. Mutation analysis of the KITLG gene was performed, but no mutation was
      found. STUDY LIMITATIONS: The new pathogenic gene was not found. CONCLUSION: A
      family with FPHH was described. Analysis revealed that its members did not have
      any mutations of the KITLG gene, which provided evidence for genetic
      heterogeneity of this genodermatosis.

PMID- 29186244
TI  - Limitation of activity and restriction of social participation in relation to age
      range, gender, and education in people with leprosy.
AB  - BACKGROUND: In Brazil, 38,000 new cases of leprosy are discovered each year,
      making it a public health problem. OBJECTIVE: To identify whether or not there is
      an association between activity limitations and the restriction of social
      participation with some demographic data (age range, gender, and education) of
      the patients in a Basic Health Unit (BHU), diagnosed with leprosy. METHODS: The
      SALSA scale was used to assess activity limitations, whereas the Participation
      scale was used to assess the restriction of social participation. RESULTS: The
      assessments were conducted with 31 BHU patients diagnosed with leprosy. Males
      were the most affected by leprosy, the multibacillary was the most prevalent, and
      education proved to be an important factor when related to the disease injuries
      among the evaluated individuals. Regarding activity limitations and the
      restriction of social participation, the percentage of individuals without
      limitations and without restrictions was greater in both scales. STUDY
      LIMITATIONS: The main limitation is the small study sample. CONCLUSION: It can be
      concluded that, for the studied sample, no association was observed between the
      activity limitations, evaluated by the Salsa scale, nor the restriction of social
      participation, evaluated by the Participation Scale, with the analyzed
      demographic data.

PMID- 29186245
TI  - Dermoscopic patterns of melanocytic nevi in children and adolescents: a cross
      sectional study.
AB  - BACKGROUND: Childhood is a dynamic period regarding nevogenesis. Dermoscopy is a
      noninvasive technique, recommended for the evaluation of pigmented cutaneous
      lesions. OBJECTIVES: The purpose of this study was to describe the structures and
      dermoscopic patterns of melanocytic nevi observed in children and adolescents.
      METHODS: Dermoscopy with photographic documentation was used for nevi located on
      the face, trunk, and extremities of 38 patients aged from one to 16 years
      examined at the Pediatric Dermatology Outpatient Clinic of the Federal University
      of Sao Paulo. RESULTS: The study included 201 skin lesions that were diagnosed as
      nevi during clinic examination. Upon evaluation of the global dermoscopic pattern
      of the lesions, the most frequently observed nevi were reticular (39.0%),
      followed by homogeneous (23.9%) and globular nevi (16.4%). During evaluation of
      the dermoscopic structures, according to the body site, the pigment network was
      the most observed in the extremities. STUDY LIMITATIONS: A limitation to be
      considered is that the inclusion of small or new lesions may hinder the
      differentiation between dots and globules. CONCLUSIONS: In our study, the most
      observed pattern was reticular. There was a difference in the predominance of
      structures dependent on the anatomical location.

PMID- 29186246
TI  - Severe cutaneous adverse drug reactions of Chinese inpatients: a meta-analysis.
AB  - BACKGROUND: The rate of severe cutaneous adverse drug reactions is low, and these
      reactions can result in death or disability. An evidence-based epidemiological
      study of severe cutaneous adverse drug reactions in China has not been reported.
      OBJECTIVE: The aim of this study was to analyze epidemiology and characteristics
      of severe cutaneous adverse drug reactions of Chinese inpatients during the
      recent 15 years with meta-analysis. METHODS: We retrospectively reviewed Chinese
      literature reporting severe cutaneous adverse drug reactions and collecting data
      from 2000 to 2015, which were in accordance with our inclusion criteria. All
      included data were analyzed with the Launch Open Meta-Analyst software. RESULTS:
      Twenty-five articles involving 928 cases with severe cutaneous adverse drug
      reactions were included. Men to women ratio was 1.14:1. Twenty-one per cent of
      the patients had drug allergy history. Antibiotics (26.0%), sedative hypnotics
      and anticonvulsants (21.6%), and antipyretic analgesics (17.1%) were the most
      common causative drugs. The most frequent clinical subtype was Stevens-Johnson
      syndrome (50.1%), followed by toxic epidermal necrolysis (25.4%), exfoliative
      dermatitis (21.0%) and drug-induced hypersensitivity syndrome (1.6%). In addition
      to skin rashes, patients with severe cutaneous adverse drug reactions suffered
      mostly from fever (73%), and blood routine abnormality (66.7%). STUDY
      LIMITATIONS: This meta-analysis is limited by its retrospective design and by its
      methodological variation. CONCLUSION: The most common causative drugs were
      antibiotics and sedative hypnotics and anticonvulsants. Stevens-Johnson syndrome
      was the most frequent clinical subtype of severe cutaneous adverse drug
      reactions. In addition to skin rashes, patients with severe cutaneous adverse
      drug reactions suffered mostly from fever, mucosal lesion, and hematologic
      abnormalities.

PMID- 29186247
TI  - A new optical intra-tissue fiber irradiation ALA-PDT in the treatment of acne
      vulgaris in rabbit model: improved safety and tolerability.
AB  - BACKGROUND: Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has
      been suggested to be effective in treatment of acne vulgaris. However, adverse
      events occur during and after treatment. OBJECTIVES: To compare the efficacy and
      tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus
      traditional ALA-PDT in treatment of acne vulgaris in rabbit models. METHODS:
      Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly
      selected to establish acne model and the other five were used as control. Rabbits
      in model group (40 ears) were further divided into four groups (10 ears/group):
      I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion
      (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control
      group without any treatment. Uncomfortable symptoms, adverse events, and
      effectiveness rates were recorded on post-treatment day 14, 30, and 45. RESULTS:
      On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was
      obviously higher than that of the other three groups (P<0.05). However, no
      improved effects were observed in OFI-ALA-PDT group on day 30 and 45. During the
      period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group
      were obviously higher than those in the other three groups (P<0.05). The adverse
      event rate in OFI-ALA-PDT group was obviously lower than that of the ALA-PDT
      group (P<0.05). STUDY LIMITATIONS: The unblindness of the study and temporary
      animal models of acne induced may hamper the assessment and monitoring of the
      results, and future studies are still needed to clarify it further. CONCLUSION:
      The OFI-ALA-PDT group (intra-tissue irradiation) showed no improved efficacy on
      treating rabbit ear acne but had higher safety and better tolerability.

PMID- 29186248
TI  - Antioxidants in dermatology.
AB  - The skin cells continuously produce, through cellular respiration, metabolic
      processes or under external aggressions, highly reactive molecules oxidation
      products, generally called free radicals. These molecules are immediately
      neutralized by enzymatic and non-enzymatic systems in a physiological and dynamic
      balance. In situations where this balance is broken, various cellular structures,
      such as the cell membrane, nuclear or mitochondrial DNA may suffer structural
      modifications, triggering or worsening skin diseases. several substances with
      alleged antioxidant effects has been offered for topical or oral use, but little
      is known about their safety, possible associations and especially their mechanism
      of action. The management of topical and oral antioxidants can help dermatologist
      to intervene in the oxidative processes safely and effectively, since they know
      the mechanisms, limitations and potential risks of using these molecules as well
      as the potential benefits of available associations.

PMID- 29186249
TI  - Tretinoin peel: a critical view.
AB  - The tretinoin peel, also known as retinoic acid peel, is a superficial peeling
      often performed in dermatological clinics in Brazil. The first study on this was
      published in 2001, by Cuce et al., as a treatment option for melasma. Since then,
      other studies have reported its applicability with reasonable methodology,
      although without a consistent scientific background and consensus. Topical
      tretinoin is used for the treatment of various dermatoses such as acne, melasma,
      scars, skin aging and non-melanoma skin cancer. The identification of retinoids
      cellular receptors was reported in 1987, but a direct cause-effect relation has
      not been established. This article reviews studies evaluating the use of topical
      tretinoin as agent for superficial chemical peel. Most of them have shown
      benefits in the treatment of melasma and skin aging. A better quality methodology
      in the study design, considering indication and intervention is indispensable
      regarding concentration, vehicle and treatment regimen (interval and number of
      applications). Additionally, more controlled and randomized studies comparing the
      treatment with tretinoin cream versus its use as a peeling agent, mainly for
      melasma and photoaging, are necessary.

PMID- 29186250
TI  - An overview about oxidation in clinical practice of skin aging.
AB  - Free radicals are unstable chemical species, highly reactive, being formed by
      cellular entities of different tissues. Increased production of these species
      without proper effective action of endogenous and exogenous antioxidant systems,
      generates a condition of oxidative stress, potentially provider of skin disorders
      that extend from functional impairments (skin cancer, dermatitis, chronic and
      acute inflammatory processes) even aesthetic character, with the destruction of
      structural proteins and cellular changes with the appearance of stains, marks and
      lines of expressions and other signs inherent to the intrinsic and extrinsic skin
      aging process. The antioxidants are chemical substances commonly used in clinical
      practice for topical application and may contribute in the fight against the
      radical species responsible for many skin damage. This paper summarized the main
      evidence of the benefits brought by the topical application of antioxidants in
      the skin, considering the amplitude of the indicative performance of antioxidant
      activity by in vitro and ex-vivo tests as well as in vivo tests. It is recognized
      that a breadth of product performance tests should be explored to truly identify
      the effectiveness of antioxidant products for an anti-aging effect.

PMID- 29186251
TI  - Histopathological diagnosis of small melanocytic lesions suspicious for malignant
      melanoma.
AB  - The concern about malignant skin neoplasms leads to the excision of smaller
      lesions. This study on small melanocytic lesions aims to evaluate the range of
      possible histopathological diagnoses, describe histopathological aspects, and
      assess the usefulness of serial histological sections. We performed a cross
      sectional descriptive histopathological study examining 76 pigmented skin lesions
      up to 6 mm in diameter. Histopathological diagnoses included atypical melanocytic
      nevi (n=38), common melanocytic nevi (n=18), atypical lentiginous melanocytic
      hyperplasia with architectural features of atypical melanocytic nevi (n=7),
      lentigo simplex (n=2), and malignant melanoma (n=1). Ten cases were non
      diagnostic. Cytological atypia was not an exclusive finding of atypical lesions.
      Examination of serial sections did not change histopathological impression. Early
      detection of malignant melanoma is important, but clinical and dermoscopy exams
      may be leading to the resection of a great number of benign lesions. Strict
      attention to histopathological criteria results in a large number of non
      diagnostic cases.

PMID- 29186252
TI  - Pigmented Kamino bodies: a little-known histological finding. Prevalence in 19
      cases of Reed nevus.
AB  - The present study aimed to determine the prevalence of Kamino bodies in Reed
      nevus, since most studies to date show conflicting data on this issue. This was a
      retrospective observational study, in which the histopathology of 19 Reed nevus
      lesions were reviewed. The slides were stained by hematoxylin and eosin and
      periodic acid-Schiff, with a special focus placed on the identification of Kamino
      bodies. Some clinical data were also collected. The median patient age was 12
      years (range of 2 to 58). The women to men ratio was 5:4. Lesions were located on
      different parts of the body. Kamino bodies were found in eleven lesions (57.89%).
      five showed pigmented Kamino bodies (26.31%), four non-pigmented Kamino bodies
      (21,05%), and 2 (10.52%) had both. Kamino bodies, pigmented or not, are a common
      histological finding in Reed nevus and may well represent a good marker to
      differentiate these from malignant melanomas.

PMID- 29186253
TI  - Crusted scabies due to indiscriminate use of glucocorticoid therapy in infant.
AB  - Crusted or Norwegian scabies is a parasitic infectious disease caused by
      Sarcoptes scabiei var. hominis that mainly affects immunocompromised individuals
      and those with neurological patients. We report a case of crusted scabies in a 4
      month-old infant who had been treated erroneously for atopic dermatitis with high
      doses of corticosteroids. This initial misdiagnosis associated with the abusive
      use of corticosteroid facilitated the evolution of scabies to crusted scabies and
      its main complications of secondary infection and sepsis.

PMID- 29186254
TI  - Merkel cell carcinoma in an immunosuppressed patient.
AB  - Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising
      incidence and an aggressive behavior. It predominantly occurs in older patients,
      with onset occurring at a mean age of 75-80 years. Recognized risk factors are
      ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell
      polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive
      patient with Merkel Cell polyomavirus detected in the tumor.

PMID- 29186255
TI  - Lepromatous leprosy simulating rheumatoid arthritis - Report of a neglected
      disease.
AB  - Brazil has the second largest number of leprosy cases in the world; nevertheless,
      late diagnosis is common. We report the case of a male patient with pain and
      numbness in both hands and feet for six years with positive rheumatoid factor and
      anticardiolipin under rheumatoid arthritis treatment for five years. Examination
      revealed diffuse cutaneous infiltration and leonine facies, characteristic
      features of lepromatous leprosy. Autoantibodies such as rheumatoid factor and
      anticardiolipin are markers of rheumatic autoimmune diseases, but their presence
      is also described in leprosy. We report the present case in order to alert health
      professionals to remember leprosy, even in areas where the disease is considered
      eliminated as a public health problem, avoiding misinterpretations of serologic
      findings and misdiagnosis.

PMID- 29186256
TI  - Angiolymphoid hyperplasia with eosinophilia versus Kimura's disease: a case
      report and a clinical and histopathological comparison.
AB  - Angiolymphoid hyperplasia with eosinophilia is a rare and benign vascular tumor
      whose etiology remains uncertain. It clinically presents itself by angiomatous
      papules or nodules located on the head and neck. Many controversies in the
      literature are found in relation to angiolymphoid hyperplasia with eosinophilia
      and Kimura's disease - its main differential diagnosis - due to their clinical
      and histopathological similarities. However, currently, most studies agree that
      they are distinct diseases. The present case illustrates a characteristic
      description of angiolymphoid hyperplasia with eosinophilia and also highlights
      the main differences with Kimura's disease.

PMID- 29186258
TI  - Vulvar melanoma: relevant aspects in therapeutic management.
AB  - Cancer of the vulva accounts for at least 1% of malignant neoplasms among women.
      Although rare, vulvar melanoma is the second most common histological type of
      vulvar cancer, representing 7-10% of all malignant vulvar neoplasms. Initial
      symptoms are non-specific and complete excision of the lesion is indicated in
      cases with suspected diagnosis. Prognosis of patients with these neoplasms is
      poor and remains unchanged despite the treatment approach. Hemivulvectomy with
      lymph node dissection is the current procedure of choice, associated or not with
      adjuvant therapies. We report two cases of patients presenting with late
      diagnosed vulvar melanoma and the relevant aspects in their therapeutic
      management.

PMID- 29186257
TI  - Lymphangioma secondary to irradiation after mastectomy.
AB  - Lymphangioma is a rare benign disease of the lymphatic vessels. Typically, they
      are primary conditions but may be acquired secondarily, such as those caused by
      irradiation during radiotherapy for the treatment of breast cancer. The local
      lymphatic obstruction provoked by irradiation causes the appearance of
      asymptomatic hyaline vesicles on the irradiated skin. The present report
      describes a 78-year-old female patient, who initially presented hyaline vesicles
      that progressed into multiple papules with serous exudation of a yellowish and
      odorless secretion on the area of chronic radiodermitis in right breast. Despite
      the rarity of the case, we emphasize the importance of knowledge regarding
      dermatological disease for early diagnosis and proper medical conduct.

PMID- 29186259
TI  - Pneumocystis jirovecii pneumonia induced by low-dose methotrexate in a patient
      with chronic urticaria.
AB  - Methotrexate has immunosuppressive effects and is administered for refractory
      chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a
      patient with refractory chronic urticaria managed by low-dose weekly methotrexate
      treatment (total cumulative dose 195mg). Our study highlights the importance of
      providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in
      patients with chronic urticaria under methotrexate therapy.

PMID- 29186260
TI  - Acute generalized exanthematous pustulosis induced by hydroxychloroquine: a case
      with atypical clinical presentation.
AB  - Acute generalized exanthematous pustulosis is a rare drug-induced eruption that
      is characterized by acute, nonfollicular sterile pustules on an erythematous and
      edematous base. The most frequently implicated drugs are beta-lactam antibiotics.
      Hydroxychloroquine has been widely used to treat dermatologic and rheumatologic
      diseases and has been reported as a rare cause of acute generalized exanthematous
      pustulosis. A 42-year-old female presented with pustular lesions on the skin
      surface with erythema, facial edema, and occasional atypical target-like lesions
      after 21 days of treatment with 200mg/day hydroxychloroquine for rheumatoid
      arthritis, diagnosed one month previously. We report a case with acute
      generalized exanthematous pustulosis induced by hydroxychloroquine and treated
      with dapsone and systemic corticosteroid.

PMID- 29186262
TI  - Solitary ulcerated plaque on the face - an unusual presentation of cutaneous
      plasmacytosis?
AB  - Cutaneous and systemic plasmacytosis is a rare disorder characterized by
      cutaneous polyclonal plasma cell infiltration frequently associated with
      polyclonal hypergammaglobulinemia and lymphadenopathy. We report a case of a 67
      year-old woman with an inflammatory ulcerated plaque in the left masseter region.
      A skin biopsy showed dense perivascular infiltrate of mature plasma cells in the
      dermis without atypia and immunoglobulin light chain restriction. After physical
      examination and further investigation, we ruled out systemic disease. Our patient
      was successfully treated only with hydrocortisone cream application. Few cases of
      isolated benign primary cutaneous plasmacytosis have been described, particularly
      in children. After excluding the diagnosis of a reactive process to an infection,
      which is unlikely in this case, we suspected of a rare manifestation of primary
      cutaneous plasmacytosis in adults with distinct presentation and clinical course.

PMID- 29186261
TI  - Cutaneous sarcoidosis and secondary open-angle glaucoma in a patient: case report
      and literature review.
AB  - The current report presents the case of a 41-year-old male patient with a two
      month history of asthenopia and plaques in the frontotemporal region. Computed
      tomography revealed bilateral hilar and mediastinal lymphadenopathy.
      Ophthalmological examination showed elevated intraocular pressure. Skin biopsy
      demonstrated aa dermal inflammatory infiltrate composed mainly of epithelioid
      cells and a few multinucleated giant cells, but no obvious lymphocytes. Findings
      of thorough physical examinations and auxiliary examinations suggested the
      presence of cutaneous sarcoidosis and secondary open-angle glaucoma. Treatment
      consisted mainly of oral methylprednisolone. Skin lesions, bilateral hilar, and
      mediastinal lymphadenopathy resolved completely. Cutaneous sarcoidosis is often
      accompanied by extracutaneous organ involvement. Dermatologists must be aware of
      the disease's extracutaneous manifestations to ensure accurate diagnosis for
      further treatments.

PMID- 29186263
TI  - White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to
      the diagnosis of superficial mycosis.
AB  - Superficial mycoses are fungal infections restricted to the stratum corneum and
      to the hair shafts, with no penetration in the epidermis; they are: white piedra,
      black piedra, tinea versicolor, and tinea nigra. This study presents images of
      mycological tests performed in the laboratory, as well as exams performed at the
      authors office, in order to improve the dermatologist's knowledge about the
      diagnosis of these dermatoses, which are common in many countries.

PMID- 29186264
TI  - Do you know this syndrome? Clouston syndrome.
AB  - Ectodermal dysplasias are conditions that present primary defects in two or more
      tissues of ectodermal origin and can be classified as hypohidrotic and hidrotic.
      Hidrotic ectodermal dysplasia or Clouston syndrome is an autosomal dominant
      genodermatosis and appears as a triad of clinical findings: palmoplantar
      keratoderma, nail dystrophy, and hypotrichosis. The hair is sparse and brittle.
      The nails become thickened and dystrophic, which is an essential characteristic
      of the syndrome. The diagnosis is made based on clinical findings. This study
      reports a case of a patient who began with changes in hair, nails and
      palmoplantar keratoderma in early childhood.

PMID- 29186265
TI  - Case for diagnosis. Patch granuloma annulare.
AB  - A 59-year-old woman reported a 20-day history of slightly scaly erythematous
      infiltrated patches on her palms and soles with a histopathological result which
      was consistent with interstitial-pattern granuloma annulare, clinically
      classified as patch granuloma annulare. This is a rare clinical variant of
      granuloma annulare, with an unknown incidence and characteristic clinical and
      histopathological features. The patient evolved with a complete remission of the
      lesions after biopsy and the use of high-potency topical corticosteroid.

PMID- 29186266
TI  - Allergy to hypoallergenic nail polish: does this exist?
AB  - The main allergen responsible for contact dermatitis to nail polish is tosylamide
      formaldehyde resin. The so-called hypoallergenic nail polishes are suposedly free
      of agents that commonly trigger reactions. The commercially available products
      and their compositions were studied. It was observed that most brands present at
      least one component capable of triggering the disease; therefore, allergic
      reaction may occur even when hypoallergenic polishes are used. There should be a
      proper investigation of the specific allergen through a patch test, because more
      than one component can cause an allergy, and we need to check the exact
      composition of each product.

PMID- 29186267
TI  - Incidence of skin diseases diagnosed in a public institution: comparison between
      2003 and 2014.
AB  - Epidemiology of diseases is influenced by population socio-demographic
      circumstances. Therefore it can be modified along the time. There are no studies
      exploring epidemiological transition in dermatology. This study investigated the
      incidence of dermatoses in new patients from a Brazilian country town public
      service in 2003 and 2014. There was a significant increase in the incidence of
      sexually transmitted diseases, leprosy, melasma, pruritus and hidradenitis
      suppurativa. However, a prominent reduction in scheduling of appointments for
      surgeries of benign lesions, drug reactions, urticaria and superficial mycoses
      was detected. The identification of epidemiological trends guides the
      dimensioning of health system and professional qualification policies.

PMID- 29186268
TI  - Quality of life in men diagnosed with anogenital warts.
AB  - Anogenital warts are a worldwide public health problem. They consist of
      epithelial proliferations caused by HPV, whose transmission occurs mainly through
      sexual intercourse. In this study, we evaluated their impact on the quality of
      life of adult males. We interviewed 88 men in an outpatient clinic for sexually
      transmitted diseases at a Brazilian public institution, using the DLQI-BRA
      questionnaire. Most patients (81%) presented mild or no impairment of quality of
      life. The main dimensions affected were sex life, symptoms, and embarrassment.
      The low impact on quality of life may well justify the delay in seeking medical
      treatment, favoring the spread of the disease.

PMID- 29186269
TI  - Aryl hydrocarbon receptor overexpression in miniaturized follicles in female
      pattern hair loss.
AB  - The etiopathogenesis of female pattern hair loss is still poorly understood. In
      addition to genetic and hormonal elements, environmental factors could be
      involved. The aryl hydrocarbon receptor is expressed in keratinocytes and can be
      activated by environmental pollutants leading to alterations in the cell cycle,
      inflammation, and apoptosis. Here we demonstrate the overexpression of nuclear
      aryl hydrocarbon receptors in miniaturized hair follicles in female pattern hair
      loss.

PMID- 29186270
TI  - Primary cutaneous amyloidosis of the auricular concha - case report.

PMID- 29186271
TI  - Interstitial granulomatous dermatitis with arthritis.

PMID- 29186273
TI  - Granulomatosis disciformis in a non-diabetic patient.

PMID- 29186272
TI  - Eczema craquele associated with antiviral treatment for chronic hepatitis C.

PMID- 29186274
TI  - Erythematous, vesicular, and circinate lesions in a 78-year-old female - benign
      familial pemphigus.

PMID- 29186276
TI  - A case of unilateral blaschkoid lichen planus pigmentosus.

PMID- 29186275
TI  - Cutaneous schwannoma: an atypical presentation.

PMID- 29186277
TI  - Getting More Clinically Meaningful Measures of Functional Impairment for
      Alzheimer's Disease.

PMID- 29186278
TI  - Dependence Levels as Interim Clinical Milestones Along the Continuum of
      Alzheimer's Disease: 18-Month Results from the GERAS Observational Study.
AB  - BACKGROUND: While functional loss forms part of the current diagnostic criteria
      used to identify dementia due to Alzheimer's disease, the gradual and progressive
      nature of the disease makes it difficult to recognize clinically relevant
      signposts that could be helpful in making treatment and management decisions.
      Having previously observed a significant relationship between stages of
      functional dependence (the level of assistance patients require consequent to
      Alzheimer's disease deficits, derived from the Alzheimer's Disease Cooperative
      Study - Activities of Daily Living Scale) and cognitive severity, we investigated
      whether measures of functional dependence could be utilized to identify clinical
      milestones of Alzheimer's disease progression. OBJECTIVES: To describe the
      patterns of change in dependence over the course of 18 months in groups
      stratified according to cognitive Alzheimer's disease dementia severity
      (determined using the Mini-Mental State Examination score) and to identify
      characteristics associated with patients showing worsening dependence
      (progressors) versus those showing no change or improvement (non-progressors).
      DESIGN: Analysis of longitudinal data from the GERAS study. SETTING: GERAS is an
      18-month prospective, multicenter, naturalistic, observational cohort study
      reflecting the routine care of patients with Alzheimer's disease in France,
      Germany, and the United Kingdom. PARTICIPANTS: 1495 community-living patients,
      aged >=55 years, diagnosed with probable Alzheimer's disease dementia, and their
      caregivers. MEASUREMENTS: Dependence levels, cognitive function, behavioral
      symptoms, caregiver burden, and cost were assessed at baseline and at 18 months.
      RESULTS: Of 971 patients having both baseline and 18-month data, 42% (408) were
      progressors and 563 (58%) were non-progressors. This general pattern held for all
      three levels of baseline Alzheimer's disease dementia severity - mild (Mini
      Mental State Examination score 21-26), moderate (15-20) or moderately
      severe/severe (<15) - with 40-45% of each group identified as progressors and 55
      60% as non-progressors. No baseline differences were seen between progressors and
      non-progressors in cognitive scores or behavioral symptoms, although progressors
      had significantly shorter times since diagnosis and showed milder functional
      impairment. Baseline factors predictive of increasing dependence over 18 months
      included more severe cognitive impairment, living with others, and having
      multiple caregivers. A higher level of initial dependence was associated with
      less risk of dependence progression. Total societal costs of care also increased
      with greater dependence. CONCLUSIONS: In this large cohort, 42% of Alzheimer's
      disease dementia patients at all levels of cognitive severity became more
      dependent within 18 months of observation while 58% did not progress. Dependence
      levels may be considered as meaningful interim clinical milestones that reflect
      Alzheimer's disease-related functional deficits, although a time frame that
      extends beyond 18 months may be necessary to observe changes if used in clinical
      trials or other longitudinal studies. Recognition of predictors of greater
      dependence offers opportunities for intervention.

PMID- 29186279
TI  - Albumin, Hemoglobin, and the Trajectory of Cognitive Function in Community
      Dwelling Older Japanese: A 13-Year Longitudinal Study.
AB  - BACKGROUND: Cognitive function can substantially decline over a long period, and
      understanding the trajectory of cognitive function is important. However, little
      is known about the linkage between nutritional biomarkers and long-term cognitive
      change. OBJECTIVES: We analyzed 13-year longitudinal data for older Japanese to
      examine the associations of serum albumin and hemoglobin levels with the
      trajectory of cognitive function. DESIGN: Longitudinal study. SETTING: Community
      based. PARTICIPANTS: A total of 1,744 community-dwelling adults aged 65 years or
      older who participated in annual health examinations in Kusatsu town, Gunma
      Prefecture, Japan, from 2002-2014. MEASUREMENTS: Cognitive function was assessed
      annually by the Mini-Mental State Examination (MMSE). Albumin and hemoglobin
      levels at baseline (the year when a respondent first participated in the health
      examination) were divided into quartiles. Hierarchical linear modeling was used
      to analyze intrapersonal and interpersonal differences in cognitive function.
      RESULTS: Participants' MMSE scores decreased at an accelerated rate over the 13
      year period. Participants with the lowest baseline albumin level (below the first
      quartile line) showed a greater accelerated decline in MMSE scores over time,
      compared with those with the highest level (above the third quartile line).
      Moreover, MMSE scores in participants with a lower hemoglobin level and lower
      MMSE score at baseline tended to decline faster over time at an accelerated rate.
      CONCLUSIONS: These findings yield new insights about the complex and diverse
      roles of these nutritional biomarkers on the trajectory of cognitive function in
      old age.

PMID- 29186280
TI  - FACEHBI: A Prospective Study of Risk Factors, Biomarkers and Cognition in a
      Cohort of Individuals with Subjective Cognitive Decline. Study Rationale and
      Research Protocols.
AB  - BACKGROUND: Long-term longitudinal studies with multimodal biomarkers are needed
      to delve into the knowledge of preclinical AD. Subjective cognitive decline has
      been proposed as a risk factor for the development of cognitive impairment. Thus,
      including individuals with SCD in observational studies may be a cost-effective
      strategy to increase the prevalence of preclinical AD in the sample. OBJECTIVES:
      To describe the rationale, research protocols and baseline characteristics of
      participants in the Fundacio ACE Healthy Brain Initiative (FACEHBI). DESIGN:
      FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term
      observational study of individuals with SCD. SETTING: Participants have been
      recruited at the memory clinic of Fundacio ACE (Barcelona) from two different
      sources: patients referred by a general practitioner and individuals from an Open
      House Initiative. PARTICIPANTS: 200 individuals diagnosed with SCD with a
      strictly normal performance in a comprehensive neuropsychological battery.
      MEASUREMENTS: Individuals will undergo an extensive neuropsychological protocol,
      risk factor assessment and a set of multimodal biomarkers including florbetaben
      PET, structural and functional MRI, diffusion tensor imaging, determination of
      amyloid species in plasma and neurophthalmologic assessment with optical
      coherence tomography. RESULTS: Two hundred individuals have been recruited in 15
      months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of
      education. CONCLUSIONS: FACEHBI is a long-term study of cognition, biomarkers and
      lifestyle that has been designed upon an innovative symptom-based approach using
      SCD as target population. It will shed light on the pathophysiology of
      preclinical AD and the role of SCD as a risk marker for the development of
      cognitive impairment.

PMID- 29186281
TI  - EU/US/CTAD Task Force: Lessons Learned from Recent and Current Alzheimer's
      Prevention Trials.
AB  - At a meeting of the EU/US/Clinical Trials in Alzheimer's Disease (CTAD) Task
      Force in December 2016, an international group of investigators from industry,
      academia, and regulatory agencies reviewed lessons learned from ongoing and
      planned prevention trials, which will help guide future clinical trials of AD
      treatments, particularly in the pre-clinical space. The Task Force discussed
      challenges that need to be addressed across all aspects of clinical trials,
      calling for innovation in recruitment and retention, infrastructure development,
      and the selection of outcome measures. While cognitive change provides a marker
      of disease progression across the disease continuum, there remains a need to
      identify the optimal assessment tools that provide clinically meaningful
      endpoints. Patient- and informant-reported assessments of cognition and function
      may be useful but present additional challenges. Imaging and other biomarkers are
      also essential to maximize the efficiency of and the information learned from
      clinical trials.

PMID- 29186282
TI  - Ethical Issues in the Development of Readiness Cohorts in Alzheimer's Disease
      Research.
AB  - There is growing interest in the development of novel approaches to secondary
      prevention trials in Alzheimer's disease to facilitate screening and recruitment
      of research participants and to reduce the time and costs associated with
      clinical trials. Several international research collaborations are setting up
      research infrastructures that link existing research cohorts, studies or patient
      registries to establish 'trial-ready' or 'readiness' cohorts. From these cohorts,
      individuals are recruited into clinical trial platforms. In setting up such
      research infrastructures, researchers must make ethically challenging design
      decisions in at least three areas: re-contacting participants in existing
      research studies, obtaining informed consent for participation in a readiness
      cohort, and disclosure of Alzheimer's disease-related biomarkers. These ethical
      considerations have been examined by a dedicated workgroup within the European
      Prevention of Alzheimer's Dementia (EPAD) project, a trans-European longitudinal
      cohort and adaptive proof-of-concept clinical trial platform. This paper offers
      recommendations for the ethical management of re-contact, informed consent and
      risk disclosure which may be of value to other research collaborations in the
      process of developing readiness cohorts for prevention trials in Alzheimer's
      disease and other disease areas.

PMID- 29186283
TI  - Intracellular trafficking of transforming growth factor beta receptors.
AB  - Transforming growth factor beta (TGFbeta) family members signal via
      heterotetrameric complexes of type I (TbetaRI) and type II (TbetaRII) dual
      specificity kinase receptors. The availability of the receptors on the cell
      surface is controlled by several mechanisms. Newly synthesized TbetaRI and
      TbetaRII are delivered from the Golgi apparatus to the cell surface via separate
      routes. On the cell surface, TGFbeta receptors are distributed between different
      microdomains of the plasma membrane and can be internalized via clathrin- and
      caveolae-mediated endocytic mechanisms. Although receptor endocytosis is not
      essential for TGFbeta signaling, localization of the activated receptor complexes
      on the early endosomes promotes TGFbeta-induced Smad activation. Caveolae
      mediated endocytosis, which is widely regarded as a mechanism that facilitates
      the degradation of TGFbeta receptors, has been shown to be required for TGFbeta
      signaling via non-Smad pathways. The importance of proper control of TGFbeta
      receptor intracellular trafficking is emphasized by clinical data, as
      mislocalization of receptors has been described in connection with several human
      diseases. Thus, control of intracellular trafficking of the TGFbeta receptors
      together with the regulation of their expression, posttranslational modifications
      and down-regulation, ensure proper regulation of TGFbeta signaling.

PMID- 29186284
TI  - CALQ: compression of quality values of aligned sequencing data.
AB  - Motivation: Recent advancements in high-throughput sequencing technology have led
      to a rapid growth of genomic data. Several lossless compression schemes have been
      proposed for the coding of such data present in the form of raw FASTQ files and
      aligned SAM/BAM files. However, due to their high entropy, losslessly compressed
      quality values account for about 80% of the size of compressed files. For the
      quality values, we present a novel lossy compression scheme named CALQ. By
      controlling the coarseness of quality value quantization with a statistical
      genotyping model, we minimize the impact of the introduced distortion on
      downstream analyses. Results: We analyze the performance of several lossy
      compressors for quality values in terms of trade-off between the achieved
      compressed size (in bits per quality value) and the Precision and Recall achieved
      after running a variant calling pipeline over sequencing data of the well-known
      NA12878 individual. By compressing and reconstructing quality values with CALQ,
      we observe a better average variant calling performance than with the original
      data while achieving a size reduction of about one order of magnitude with
      respect to the state-of-the-art lossless compressors. Furthermore, we show that
      CALQ performs as good as or better than the state-of-the-art lossy compressors in
      terms of variant calling Recall and Precision for most of the analyzed datasets.
      Availability and implementation: CALQ is written in C ++ and can be downloaded
      from https://github.com/voges/calq. Contact: voges@tnt.uni-hannover.de or
      mhernaez@illinois.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29186285
TI  - Myriads: P-value-based multiple testing correction.
AB  - Motivation: There are many multiple testing correction methods. Some of them are
      robust to various dependencies in the data while others are not. Some of the
      implementations have problems for managing high dimensional list of P-values as
      currently demanded by microarray and other omic technologies. Results: The
      program Myriads, formerly SGoF+, provides some of the most important P-value
      based correction methods jointly with a test of dependency and a P-value
      simulator. Myriads easily manage hundreds of thousands of P-values. Availability
      and implementation: http://myriads.webs.uvigo.es. Contact: myriads@uvigo.es.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29186286
TI  - Obesity-induced changes in hepatic and placental clock gene networks in rat
      pregnancy.
AB  - Maternal obesity induces pregnancy complications and disturbs fetal development,
      but the specific mechanisms underlying these outcomes are unclear. Circadian
      rhythms are implicated in metabolic complications associated with obesity, and
      maternal metabolic adaptations to pregnancy. Accordingly, obesity-induced
      circadian dysfunction may drive adverse outcomes in obese pregnancy. This study
      investigated whether maternal obesity alters the rhythmic expression of clock
      genes and associated nuclear receptors across maternal, fetal, and placental
      tissues. Wistar rats were maintained on a cafeteria (CAF) diet prior to and
      throughout gestation to induce maternal obesity. Maternal and fetal liver and
      placental labyrinth zone (LZ) were collected at four-hourly time points across
      days 15-16 and 21-22 of gestation (term = 23 days). Gene expression was analyzed
      by RT-qPCR. Expression of the accessory clock gene Nr1d1 was rhythmic in the
      maternal and fetal liver and LZ of chow-fed controls, but in each case CAF
      feeding reduced peak Nr1d1 expression. Obesity resulted in a phase advance
      (approx. 1.5 h) in the rhythms of several clock genes and Ppar-delta in maternal
      liver. Aside from Nr1d1, expression of clock genes was mostly arrhythmic in LZ
      and fetal liver, and was unaffected by the CAF diet. In conclusion, maternal
      obesity suppressed Nr1d1 expression across maternal, fetal, and placental
      compartments and phase-advanced the rhythms of maternal hepatic clock genes.
      Given the key role of Nr1d1 in regulating metabolic, vascular, and inflammatory
      processes, our data suggest that disruptions to rhythmic Nr1d1 expression in
      utero may contribute to programmed health complications in offspring of obese
      pregnancies.

PMID- 29186287
TI  - Utility of the Personality Assessment Inventory in detecting feigned Attention
      Deficit/Hyperactivity Disorder (ADHD): The Feigned Adult ADHD index.
AB  - Objective: The high potential for secondary gain among college students
      presenting for Attention-Deficit/Hyperactivity Disorder (ADHD) evaluations
      highlights the need for psychometrically sound embedded validity indicators. The
      purpose of this study was to develop new validity indicators specific to feigned
      ADHD for the Personality Assessment Inventory (PAI) and compare them to
      preexisting imbedded PAI validity measures. Method: PAI scales that were
      theoretically related to feigned ADHD were evaluated. A binomial (ADHD
      simulators, n = 138, and genuine ADHD, n = 142) logistic regression was conducted
      with selected PAI scales and subscales. Classification rates were compared
      between the new and existing validity scales. A similar approach was used for
      item-level data in a second study in a subgroup of the original sample. Results:
      The derived PAI scale-based logistic regression had a sensitivity of 54% and
      specificity of 92%. This algorithm accurately identified 97% of healthy controls
      as not feigning ADHD and correctly identified 98% of a no diagnosis group and 75%
      of a mood/anxiety disorders group. Classification accuracy of the new index was
      superior to the majority of existing PAI validity scales across groups. An item
      level PAI algorithm had a sensitivity of 85% and specificity of 97% for
      identifying feigned ADHD. Conclusions: New validity measures were compared to
      existing PAI validity indicators and performed better than many of them in this
      study. The algorithms developed in this study of ADHD simulators and genuine ADHD
      cases have adequate sensitivity and good specificity and appear to function
      differently than other PAI symptom validity scales.

PMID- 29186288
TI  - Reproducible and flexible simulation experiments with ML-Rules and SESSL.
AB  - Summary: The modeling language ML-Rules allows specifying and simulating complex
      systems biology models at multiple levels of organization. The development of
      such simulation models involves a wide variety of simulation experiments and the
      replicability of generated simulation results requires suitable means for
      documenting simulation experiments. Embedded domain-specific languages, such as
      SESSL, cater both requirements. With SESSL, the user can integrate diverse
      simulation experimentation methods and third-party software components into an
      executable, readable simulation experiment specification. A newly developed SESSL
      binding for ML-Rules exploits these features of SESSL, opening up new
      possibilities for executing and documenting simulation experiments with ML-Rules
      models. Availability and Implementation: ML-Rules is implemented in Java, SESSL
      and its bindings are implemented in Scala. The source code is available under
      open-source licenses: ML-Rulesgit.informatik.uni-rostock.de/mosi/mlrules2ML-Rules
      Quickstart (Graphical Editor)git.informatik.uni-rostock.de/mosi/mlrules2
      quickstartSESSLgit.informatik.uni-rostock.de/mosi/sessl and sessl.orgSESSL
      Quickstart (Experiment Template)git.informatik.uni-rostock.de/mosi/sessl
      quickstart Furthermore, Maven-compatible compiled packages of ML-Rules, SESSL,
      and the SESSL bindings are available from the Maven Central Repository at
      maven.org (org.sessl:* and org.jamesii:mlrules). Supplementary Material: The
      supplementary material contains a more complex case study that exemplifies the
      usage of the SESSL binding for ML-Rules. Contact: tom.warnke@uni-rostock.de.

PMID- 29186289
TI  - Discharge Criteria for Patient With Lassa Fever Infection.

PMID- 29186290
TI  - scHiCNorm: a software package to eliminate systematic biases in single-cell Hi-C
      data.
AB  - Summary: We build a software package scHiCNorm that uses zero-inflated and hurdle
      models to remove biases from single-cell Hi-C data. Our evaluations prove that
      our models can effectively eliminate systematic biases for single-cell Hi-C data,
      which better reveal cell-to-cell variances in terms of chromosomal structures.
      Availability and implementation: scHiCNorm is available at
      http://dna.cs.miami.edu/scHiCNorm/. Perl scripts are provided that can generate
      bias features. Pre-built bias features for human (hg19 and hg38) and mouse (mm9
      and mm10) are available to download. R scripts can be downloaded to remove
      biases. Contact: zheng.wang@miami.edu. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29186291
TI  - Sex Differences in the Behavioral Desensitization of Water Intake Observed After
      Repeated Central Injections of Angiotensin II.
AB  - Previous in vivo and in vitro studies demonstrate that the angiotensin type 1
      receptor rapidly desensitizes after exposure to angiotensin II (AngII).
      Behaviorally, this likely underlies the reduced drinking observed after acute
      repeated central injections of AngII. To date, this phenomenon has been studied
      exclusively in male subjects. Because there are sex differences in the dipsogenic
      potency of AngII, we hypothesized that sex differences also exist in
      desensitization caused by AngII. As expected, when male rats were pretreated with
      AngII, they drank less water after a test injection of AngII than did rats
      pretreated with vehicle. Intact cycling female rats, however, drank similar
      amounts of water after AngII regardless of the pretreatment. To probe the
      mechanism underlying this sex difference, we tested the role of gonadal hormones
      in adult and developing rats. Gonadectomy in adults did not produce a male-like
      propensity for desensitization of water intake in female rats, nor did it produce
      a female-like response in male rats. To test if neonatal brain masculinization
      generated a male-like responsiveness, female pups were treated at birth with
      vehicle, testosterone propionate (TP), or dihydrotestosterone (DHT). When tested
      as adults, TP-treated female rats showed a male-like desensitization after
      repeated AngII that was not found in vehicle- or DHT-treated rats. Together,
      these data reveal a striking sex difference in the behavioral response to
      elevated AngII that is mediated by organizational effects of gonadal hormones and
      provide an example of one of the many ways that sex influences the renin
      angiotensin-aldosterone system.

PMID- 29186293
TI  - Early histone H4 acetylation during chromatin remodeling in equine
      spermatogenesis.
AB  - Chromatin remodeling during spermatogenesis culminates in the exchange of
      nucleosomes for transition proteins and protamines as an important part of
      spermatid development to give rise to healthy sperm. Comparative
      immunofluorescence analyses of equine and murine testis histological sections
      were used to characterize nucleoprotein exchange in the stallion. Histone H4
      hyperacetylation is considered a key event of histone removal during the
      nucleoprotein transition to a protamine-based sperm chromatin structure. In the
      stallion, but not the mouse, H4 was already highly acetylated in lysine residues
      K5, K8, and K12 in round spermatids almost immediately after meiotic division.
      Time courses of transition protein 1 (TP1), protamine 1, H2A histone family
      member Z (H2AFZ), and testis-specific histone H2B variant (TH2B) expression in
      stallion spermatogenesis were similar to the mouse where protamine 1 and TP1 were
      only expressed in elongating spermatids much later in spermatid development. The
      additional acetylation of H4 in K16 position (H4K16ac) was detected during a
      brief phase of spermatid elongation in both species, concomitant with the
      phosphorylation of the noncanonical histone variant H2AFX resulting from DNA
      strand break-mediated DNA relaxation. The results suggest that H4K16 acetylation,
      which is dependent on DNA damage signaling, may be more important for nucleosome
      replacement in spermiogenesis than indicated by data obtained in rodents and
      highlight the value of the stallion as an alternative animal model for
      investigating human spermatogenesis. A revised classification system of the
      equine spermatogenic cycle for simplified comparison with the mouse is proposed
      to this end.

PMID- 29186292
TI  - SATORI: a system for ontology-guided visual exploration of biomedical data
      repositories.
AB  - Motivation: The ever-increasing number of biomedical datasets provides tremendous
      opportunities for re-use but current data repositories provide limited means of
      exploration apart from text-based search. Ontological metadata annotations
      provide context by semantically relating datasets. Visualizing this rich network
      of relationships can improve the explorability of large data repositories and
      help researchers find datasets of interest. Results: We developed SATORI-an
      integrative search and visual exploration interface for the exploration of
      biomedical data repositories. The design is informed by a requirements analysis
      through a series of semi-structured interviews. We evaluated the implementation
      of SATORI in a field study on a real-world data collection. SATORI enables
      researchers to seamlessly search, browse and semantically query data repositories
      via two visualizations that are highly interconnected with a powerful search
      interface. Availability and implementation: SATORI is an open-source web
      application, which is freely available at http://satori.refinery-platform.org and
      integrated into the Refinery Platform. Contact: nils@hms.harvard.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29186294
TI  - Classifying next-generation sequencing data using a zero-inflated Poisson model.
AB  - Motivation: With the development of high-throughput techniques, RNA-sequencing
      (RNA-seq) is becoming increasingly popular as an alternative for gene expression
      analysis, such as RNAs profiling and classification. Identifying which type of
      diseases a new patient belongs to with RNA-seq data has been recognized as a
      vital problem in medical research. As RNA-seq data are discrete, statistical
      methods developed for classifying microarray data cannot be readily applied for
      RNA-seq data classification. Witten proposed a Poisson linear discriminant
      analysis (PLDA) to classify the RNA-seq data in 2011. Note, however, that the
      count datasets are frequently characterized by excess zeros in real RNA-seq or
      microRNA sequence data (i.e. when the sequence depth is not enough or small RNAs
      with the length of 18-30 nucleotides). Therefore, it is desired to develop a new
      model to analyze RNA-seq data with an excess of zeros. Results: In this paper, we
      propose a Zero-Inflated Poisson Logistic Discriminant Analysis (ZIPLDA) for RNA
      seq data with an excess of zeros. The new method assumes that the data are from a
      mixture of two distributions: one is a point mass at zero, and the other follows
      a Poisson distribution. We then consider a logistic relation between the
      probability of observing zeros and the mean of the genes and the sequencing depth
      in the model. Simulation studies show that the proposed method performs better
      than, or at least as well as, the existing methods in a wide range of settings.
      Two real datasets including a breast cancer RNA-seq dataset and a microRNA-seq
      dataset are also analyzed, and they coincide with the simulation results that our
      proposed method outperforms the existing competitors. Availability and
      implementation: The software is available at http://www.math.hkbu.edu.hk/~tongt.
      Contact: xwan@comp.hkbu.edu.hk or tongt@hkbu.edu.hk. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29186295
TI  - Systematic analysis and prediction of type IV secreted effector proteins by
      machine learning approaches.
AB  - In the course of infecting their hosts, pathogenic bacteria secrete numerous
      effectors, namely, bacterial proteins that pervert host cell biology. Many Gram
      negative bacteria, including context-dependent human pathogens, use a type IV
      secretion system (T4SS) to translocate effectors directly into the cytosol of
      host cells. Various type IV secreted effectors (T4SEs) have been experimentally
      validated to play crucial roles in virulence by manipulating host cell gene
      expression and other processes. Consequently, the identification of novel
      effector proteins is an important step in increasing our understanding of host
      pathogen interactions and bacterial pathogenesis. Here, we train and compare six
      machine learning models, namely, Naive Bayes (NB), K-nearest neighbor (KNN),
      logistic regression (LR), random forest (RF), support vector machines (SVMs) and
      multilayer perceptron (MLP), for the identification of T4SEs using 10 types of
      selected features and 5-fold cross-validation. Our study shows that: (1)
      including different but complementary features generally enhance the predictive
      performance of T4SEs; (2) ensemble models, obtained by integrating individual
      single-feature models, exhibit a significantly improved predictive performance
      and (3) the 'majority voting strategy' led to a more stable and accurate
      classification performance when applied to predicting an ensemble learning model
      with distinct single features. We further developed a new method to effectively
      predict T4SEs, Bastion4 (Bacterial secretion effector predictor for T4SS), and we
      show our ensemble classifier clearly outperforms two recent prediction tools. In
      summary, we developed a state-of-the-art T4SE predictor by conducting a
      comprehensive performance evaluation of different machine learning algorithms
      along with a detailed analysis of single- and multi-feature selections.

PMID- 29186296
TI  - Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve
      the chance for success?
AB  - The success of targeted therapies, including inhibitors of the vascular
      endothelial growth factor pathway or the mammalian target of rapamycin, in the
      treatment of metastatic renal cell carcinoma led to interest in testing their
      efficacy in the adjuvant setting. Results from the first trials are now
      available, with other studies due to report imminently. This review provides an
      overview of adjuvant targeted therapy in renal cell carcinoma, including
      interpretation of currently available conflicting data and future direction of
      research. We discuss the key differences between the completed targeted therapy
      adjuvant trials, and highlight the importance of accurately identifying patients
      who are likely to benefit from adjuvant treatment. We also consider reasons why
      blinded independent radiology review and treatment dose may prove critical for
      adjuvant treatment success. The implications of using disease-free survival as a
      surrogate end point for overall survival from the patient perspective and
      measurement of health benefit have recently been brought into focus and are
      discussed. Finally, we discuss how the ongoing adjuvant trials with targeted
      therapies and checkpoint inhibitors may improve our understanding and ability to
      prevent tumor recurrence after nephrectomy in the future.

PMID- 29186298
TI  - SimulaTE: simulating complex landscapes of transposable elements of populations.
AB  - Motivation: Estimating the abundance of transposable elements (TEs) in
      populations (or tissues) promises to answer many open research questions.
      However, progress is hampered by the lack of concordance between different
      approaches for TE identification and thus potentially unreliable results.
      Results: To address this problem, we developed SimulaTE a tool that generates TE
      landscapes for populations using a newly developed domain specific language
      (DSL). The simple syntax of our DSL allows for easily building even complex TE
      landscapes that have, for example, nested, truncated and highly diverged TE
      insertions. Reads may be simulated for the populations using different sequencing
      technologies (PacBio, Illumina paired-ends) and strategies (sequencing
      individuals and pooled populations). The comparison between the expected (i.e.
      simulated) and the observed results will guide researchers in finding the most
      suitable approach for a particular research question. Availability and
      implementation: SimulaTE is implemented in Python and available at
      https://sourceforge.net/projects/simulates/. Manual
      https://sourceforge.net/p/simulates/wiki/Home/#manual; Test data and tutorials
      https://sourceforge.net/p/simulates/wiki/Home/#walkthrough; Validation
      https://sourceforge.net/p/simulates/wiki/Home/#validation. Contact:
      robert.kofler@vetmeduni.ac.at.

PMID- 29186299
TI  - Within-plant variation in seed size and inflorescence fecundity is associated
      with epigenetic mosaicism in the shrub Lavandula latifolia (Lamiaceae).
AB  - Background and Aims: Sub-individual variation in traits of homologous structures
      has multiple ecological consequences for individuals and populations. Assessing
      the evolutionary significance of such effects requires an improved knowledge of
      the mechanisms underlying within-plant phenotypic heterogeneity. The hypothesis
      that continuous within-plant variation in some phenotypic traits can be
      associated with epigenetic mosaicism was examined. Methods: Fifteen individuals
      of the long-lived, evergreen Mediterranean shrub Lavandula latifolia were
      studied. Five widely spaced 'modules', each consisting of a single inflorescence
      plus all its subtending basal leaves, were collected from each shrub. Genomic DNA
      was extracted from leaf samples and genome-wide cytosine methylation determined
      by reversed phase high-performance liquid chromatography (HPLC) with
      spectrofluorimetric detection. The number and mean mass of seeds produced were
      determined for each inflorescence. An assessment was made of whether (1) leaves
      from different modules in the same plant differed significantly in global DNA
      cytosine methylation, and (2) mosaicism in cytosine methylation contributed to
      explain variation across modules in number and size of seeds. Key Results: Leaves
      from different modules in the same plant differed in global DNA cytosine
      methylation. The magnitude of epigenetic mosaicism was substantial, as the
      variance in DNA methylation among modules of the same shrub was greater than the
      variance between individuals. Number and mean mass of seeds produced by
      individual inflorescences varied within plants and were quadratically related to
      cytosine methylation of subtending leaves, with an optimum at an intermediate
      methylation level (approx. 25 %). Conclusions: The results support a causal link
      between global cytosine methylation of leaves in a module and the size and
      numbers of seeds produced by the associated inflorescence. It is proposed that
      variation in global DNA methylation within L. latifolia shrubs may result from
      the concerted action of plant sectoriality and differential exposure of different
      plant parts to some environmental factor(s) with a capacity to induce durable
      epigenetic changes.

PMID- 29186300
TI  - Unsweetening the Heart: Possible Pleiotropic Effects of SGLT2 Inhibitors on
      Cardio and Cerebrovascular Alterations in Resistant Hypertensive Subjects.
AB  - Resistant hypertension (RH) is a multifactorial disease associated with several
      target organ damage, such as microalbuminuria, left ventricular hypertrophy, and
      arterial stiffness. These subjects have high cardiovascular complications,
      especially when associated with diabetes condition. Sodium glucose cotransporter
      2 (SGLT-2) inhibitors represent a new class of oral antidiabetic drugs that have
      shown positive effects in diabetics and even hypertensives subjects. Several
      studies demonstrated positive outcomes related to blood pressure levels, body
      weight, and glycemic control. Also found a reduction on microalbuminuria, cardiac
      and arterial remodeling process, and decrease in hospitalization care due heart
      failure. Despite these positive effects, the outcomes found for stroke were
      conflicted and tend neutral effect. Based on this, we sought to assess the
      pleiotropic effects of SGLT-2 inhibitors and the possible impact in RH subjects.
      In order to analyze the prospects of SGLT-2 inhibitors as a possible medication
      to complement the therapy manage of this high-risk class of patients.

PMID- 29186297
TI  - Noncoding RNAs in Cardiovascular Disease: Pathological Relevance and Emerging
      Role as Biomarkers and Therapeutics.
AB  - Noncoding RNAs (ncRNA) include a diverse range of functional RNA species
      microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) being most studied in
      pathophysiology. Cardiovascular morbidity is associated with differential
      expression of myriad miRNAs; miR-21, miR-155, miR-126, miR-146a/b, miR-143/145,
      miR-223, and miR-221 are the top 9 most reported miRNAs in hypertension and
      atherosclerotic disease. A single miRNA may have hundreds of messenger RNA
      targets, which makes a full appreciation of the physiologic ramifications of such
      broad-ranging effects a challenge. miR-21 is the most prominent ncRNA associated
      with hypertension and atherosclerotic disease due to its role as a "mechano-miR",
      responding to arterial shear stresses. "Immuno-miRs", such as miR-155 and miR
      223, affect cardiovascular disease (CVD) via regulation of hematopoietic cell
      differentiation, chemotaxis, and activation in response to many pro-atherogenic
      stimuli. "Myo-miRs", such as miR-1 and miR-133, affect cardiac muscle plasticity
      and remodeling in response to mechanical overload. This in-depth review analyzes
      observational and experimental reports of ncRNAs in CVD, including future
      applications of ncRNA-based strategies in diagnosis, prediction (e.g., survival
      and response to small molecule therapy), and biologic therapy.

PMID- 29186302
TI  - Translational bioinformatics in mental health: open access data sources and
      computational biomarker discovery.
AB  - Mental illness is increasingly recognized as both a significant cost to society
      and a significant area of opportunity for biological breakthrough. As -omics and
      imaging technologies enable researchers to probe molecular and physiological
      underpinnings of multiple diseases, opportunities arise to explore the biological
      basis for behavioral health and disease. From individual investigators to large
      international consortia, researchers have generated rich data sets in the area of
      mental health, including genomic, transcriptomic, metabolomic, proteomic,
      clinical and imaging resources. General data repositories such as the Gene
      Expression Omnibus (GEO) and Database of Genotypes and Phenotypes (dbGaP) and
      mental health (MH)-specific initiatives, such as the Psychiatric Genomics
      Consortium, MH Research Network and PsychENCODE represent a wealth of information
      yet to be gleaned. At the same time, novel approaches to integrate and analyze
      data sets are enabling important discoveries in the area of mental and behavioral
      health. This review will discuss and catalog into an organizing framework the
      increasingly diverse set of MH data resources available, using schizophrenia as a
      focus area, and will describe novel and integrative approaches to molecular
      biomarker discovery that make use of mental health data.

PMID- 29186304
TI  - Construction of a hierarchical gene regulatory network centered around a
      transcription factor.
AB  - We have modified a multitude of transcription factors (TFs) in numerous plant
      species and some animal species, and obtained transgenic lines that exhibit
      phenotypic alterations. Whenever we observe phenotypic changes in a TF's
      transgenic lines, we are always eager to identify its target genes, collaborative
      regulators and even upstream high hierarchical regulators. This issue can be
      addressed by establishing a multilayered hierarchical gene regulatory network (ML
      hGRN) centered around a given TF. In this article, a practical approach for
      constructing an ML-hGRN centered on a TF using a combined approach of top-down
      and bottom-up network construction methods is described. Strategies for
      constructing ML-hGRNs are vitally important, as these networks provide key
      information to advance our understanding of how biological processes are
      regulated.

PMID- 29186303
TI  - Lack of Association Between Maternal or Neonatal Vitamin D Status and Risk of
      Childhood Type 1 Diabetes: A Scandinavian Case-Cohort Study.
AB  - Studies on vitamin D status during pregnancy and risk of type 1 diabetes mellitus
      (T1D) lack consistency and are limited by small sample sizes or single measures
      of 25-hydroxyvitamin D (25(OH)D). We investigated whether average maternal
      25(OH)D plasma concentrations during pregnancy are associated with risk of
      childhood T1D. In a case-cohort design, we identified 459 children with T1D and a
      random sample (n = 1,561) from the Danish National Birth Cohort (n = 97,127) and
      Norwegian Mother and Child Cohort Study (n = 113,053). Participants were born
      between 1996 and 2009. The primary exposure was the estimated average 25(OH)D
      concentration, based on serial samples from the first trimester until delivery
      and on umbilical cord plasma. We estimated hazard ratios using weighted Cox
      regression adjusting for multiple confounders. The adjusted hazard ratio for T1D
      per 10-nmol/L increase in the estimated average 25(OH)D concentration was 1.00
      (95% confidence interval: 0.90, 1.10). Results were consistent in both cohorts,
      in multiple sensitivity analyses, and when we analyzed mid-pregnancy or cord
      blood separately. In conclusion, our large study demonstrated that normal
      variation in maternal or neonatal 25(OH)D is unlikely to have a clinically
      important effect on risk of childhood T1D.

PMID- 29186305
TI  - Systems Bioinformatics: increasing precision of computational diagnostics and
      therapeutics through network-based approaches.
AB  - Systems Bioinformatics is a relatively new approach, which lies in the
      intersection of systems biology and classical bioinformatics. It focuses on
      integrating information across different levels using a bottom-up approach as in
      systems biology with a data-driven top-down approach as in bioinformatics. The
      advent of omics technologies has provided the stepping-stone for the emergence of
      Systems Bioinformatics. These technologies provide a spectrum of information
      ranging from genomics, transcriptomics and proteomics to epigenomics,
      pharmacogenomics, metagenomics and metabolomics. Systems Bioinformatics is the
      framework in which systems approaches are applied to such data, setting the level
      of resolution as well as the boundary of the system of interest and studying the
      emerging properties of the system as a whole rather than the sum of the
      properties derived from the system's individual components. A key approach in
      Systems Bioinformatics is the construction of multiple networks representing each
      level of the omics spectrum and their integration in a layered network that
      exchanges information within and between layers. Here, we provide evidence on how
      Systems Bioinformatics enhances computational therapeutics and diagnostics, hence
      paving the way to precision medicine. The aim of this review is to familiarize
      the reader with the emerging field of Systems Bioinformatics and to provide a
      comprehensive overview of its current state-of-the-art methods and technologies.
      Moreover, we provide examples of success stories and case studies that utilize
      such methods and tools to significantly advance research in the fields of systems
      biology and systems medicine.

PMID- 29186301
TI  - Toenail Manganese: A Sensitive and Specific Biomarker of Exposure to Manganese in
      Career Welders.
AB  - Manganese (Mn) is an essential trace metal. It is also a component of welding
      fume. Chronic inhalation of manganese from welding fume has been associated with
      decreased neurological function. Currently, there is not a universally recognized
      biomarker for Mn exposure; however, hair and toenails have shown promise. In a
      cohort of 45 male welders and 35 age-matched factory control subjects, we
      assessed the sensitivity and specificity of toenail Mn to distinguish
      occupationally exposed subjects from unexposed controls. Further we examined the
      exposure time window that best correlates with the proposed biomarker, and
      investigated if non-occupational exposure factors impacted toenail Mn
      concentrations. Toenail clippings were analyzed for Mn using Inductively Coupled
      Plasma Mass Spectrometry (ICP-MS). Exposure to respirable Mn-containing particles
      (<4 um) was estimated using an exposure model that combines personal air
      monitoring, work history information, and dietary intake to estimate an
      individual's exposure to Mn from inhalation of welding fume. We assessed the
      group differences in toenail concentrations using a Student's t-test between
      welders and control subjects and performed a receiver operating characteristic
      (ROC) curve analysis to identify a threshold in toenail concentration that has
      the highest sensitivity and specificity in distinguishing welders from control
      subjects. Additionally, we performed mixed-model regressions to investigate the
      association between different exposure windows and toenail Mn concentrations. We
      observed that toenail Mn concentrations were significantly elevated among welders
      compared to control subjects (6.87 +/- 2.56 versus 2.70 +/- 1.70 ug g-1; P <
      0.001). Our results show that using a toenail Mn concentration of 4.14 ug g-1 as
      cutoff allows for discriminating between controls and welders with 91%
      specificity and 94% sensitivity [area under curve (AUC) = 0.98]. Additionally, we
      found that a threshold of 4.66 ug g-1 toenail Mn concentration enables a 90%
      sensitive and 90% specific discrimination (AUC = 0.96) between subjects with
      average exposure above or below the American Conference of Governmental
      Industrial Hygienist (ACGIH) Threshold Limit Value (TLV) of 0.02 mg m-3 during
      the exposure window of 7-12 months prior to the nail being clipped. Investigating
      which exposure window was best reflected by toenail Mn reproduced the result from
      another study of toenail Mn being significantly (P < 0.001) associated with
      exposure 7-12 months prior to the nail being clipped. Lastly, we found that
      dietary intake, body mass index, age, smoking status, and ethnicity had no
      significant effect on toenail Mn concentrations. Our results suggest that toenail
      Mn is a sensitive, specific, and easy-to-acquire biomarker of Mn exposure, which
      is feasible to be used in an industrial welder population.

PMID- 29186306
TI  - Antihypertensive Medications and Falls in the Elderly.

PMID- 29186307
TI  - Ultrastructure and development of non-contiguous stomatal clusters and
      helicocytic patterning in Begonia.
AB  - Background and Aims: Helicocytic stomata are characterized by an inward spiral of
      mesogenous cells surrounding a central stomatal pore. They represent a relatively
      rare feature that occurs in some drought-tolerant angiosperm species. In some
      Begonia species with thick leaves, the stomata are not only helicocytic but also
      clustered into groups that are spaced apart by at least one cell. This paper
      presents a detailed ontogenetic study of this characteristic non-contiguous
      stomatal patterning in a developmental and phylogenetic context. Methods: Light
      microscopy and both scanning and transmission electron microscopy were used to
      examine stomatal development in several species of Begonia. Published reports of
      stomatal development in Begonia and other angiosperms were reviewed to provide a
      comprehensive discussion of the evolution of stomatal patterning. Key Results:
      Helicocytic stomata develop from meristemoids that undergo a series of oriented
      asymmetric divisions to produce a spiral of mesogene stomatal lineage ground
      cells (SLGCs) surrounding a stoma. A clear developmental similarity between
      anisocytic and helicocytic stomata is positively correlated with the number of
      iterations of amplifying divisions that result in SLGCs. Stomatal clusters
      develop from asymmetric divisions in neighbouring SLGCs. Within each cluster, non
      contiguous spacing of meristemoids is maintained by asymmetric divisions oriented
      away from each developing meristemoid. Conclusions: Formation of non-contiguous
      stomatal clusters in Begonia relies on two primary developmental factors in the
      epidermis: an inwardly spiralling series of amplifying divisions that result in
      helicocytic stomata, and the development of a variable number of meristemoids
      from neighbouring SLGCs within each cluster. Optimization of these features on an
      angiosperm phylogeny indicates that the occurrence of amplifying divisions could
      be pre-adaptive for these factors. Both factors have been thoroughly studied in
      terms of developmental genetics in Arabidopsis, suggesting gene orthologues that
      could be implicated in Begonia stomatal patterning.

PMID- 29186309
TI  - The Year in Clinical Hypertension From Other Pages.

PMID- 29186308
TI  - Predicting Forearm Physical Exposures During Computer Work Using Self-Reports,
      Software-Recorded Computer Usage Patterns, and Anthropometric and Workstation
      Measurements.
AB  - Objectives: Alternative techniques to assess physical exposures, such as
      prediction models, could facilitate more efficient epidemiological assessments in
      future large cohort studies examining physical exposures in relation to work
      related musculoskeletal symptoms. The aim of this study was to evaluate two types
      of models that predict arm-wrist-hand physical exposures (i.e. muscle activity,
      wrist postures and kinematics, and keyboard and mouse forces) during computer
      use, which only differed with respect to the candidate predicting variables; (i)
      a full set of predicting variables, including self-reported factors, software
      recorded computer usage patterns, and worksite measurements of anthropometrics
      and workstation set-up (full models); and (ii) a practical set of predicting
      variables, only including the self-reported factors and software-recorded
      computer usage patterns, that are relatively easy to assess (practical models).
      Methods: Prediction models were build using data from a field study among 117
      office workers who were symptom-free at the time of measurement. Arm-wrist-hand
      physical exposures were measured for approximately two hours while workers
      performed their own computer work. Each worker's anthropometry and workstation
      set-up were measured by an experimenter, computer usage patterns were recorded
      using software and self-reported factors (including individual factors, job
      characteristics, computer work behaviours, psychosocial factors, workstation set
      up characteristics, and leisure-time activities) were collected by an online
      questionnaire. We determined the predictive quality of the models in terms of R2
      and root mean squared (RMS) values and exposure classification agreement to low-,
      medium-, and high-exposure categories (in the practical model only). Results: The
      full models had R2 values that ranged from 0.16 to 0.80, whereas for the
      practical models values ranged from 0.05 to 0.43. Interquartile ranges were not
      that different for the two models, indicating that only for some physical
      exposures the full models performed better. Relative RMS errors ranged between 5%
      and 19% for the full models, and between 10% and 19% for the practical model.
      When the predicted physical exposures were classified into low, medium, and high,
      classification agreement ranged from 26% to 71%. Conclusion: The full prediction
      models, based on self-reported factors, software-recorded computer usage
      patterns, and additional measurements of anthropometrics and workstation set-up,
      show a better predictive quality as compared to the practical models based on
      self-reported factors and recorded computer usage patterns only. However,
      predictive quality varied largely across different arm-wrist-hand exposure
      parameters. Future exploration of the relation between predicted physical
      exposure and symptoms is therefore only recommended for physical exposures that
      can be reasonably well predicted.

PMID- 29186310
TI  - New antiemetics: facing the current challenge.

PMID- 29186312
TI  - Benzodiazepines: An Old Class of New Antihypertensive Drugs?

PMID- 29186311
TI  - Unequal Exposure or Unequal Vulnerability? Contributions of Neighborhood
      Conditions and Cardiovascular Risk Factors to Socioeconomic Inequality in
      Incident Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis.
AB  - Risk factors can drive socioeconomic inequalities in cardiovascular disease (CVD)
      through differential exposure and differential vulnerability. In this paper, we
      show how econometric decomposition directly enables simultaneous, policy-oriented
      assessment of these 2 mechanisms. We specifically estimate contributions of
      neighborhood environment and proximal risk factors to socioeconomic inequality in
      CVD incidence via these mechanisms. We followed 5,608 participants in the Multi
      Ethnic Study of Atherosclerosis (2000-2012) to their first CVD event (median
      length of follow-up, 12.2 years). We used a summary measure of baseline
      socioeconomic position (SEP). Covariates included baseline demographics,
      neighborhood characteristics, and psychosocial, behavioral, and biomedical risk
      factors. Using Poisson models, we decomposed the difference (inequality) in
      incidence rates between low- and high-SEP groups into contributions of 1)
      differences in covariate means (differential exposure) and 2) differences in CVD
      risk associated with covariates (differential vulnerability). Notwithstanding
      large uncertainty in neighborhood estimates, our analysis suggested that
      differential exposure to poorer neighborhood socioeconomic conditions, adverse
      social environment, diabetes, and hypertension accounted for most of the
      inequality. Psychosocial and behavioral contributions were negligible. Further,
      neighborhood SEP, female sex, and white race were more strongly associated with
      CVD among low-SEP (vs. high-SEP) participants. These differentials in
      vulnerability also accounted for nontrivial portions of the inequality and could
      have important implications for intervention.

PMID- 29186313
TI  - The Latent Structure and Test-Retest Stability of Connected Language Measures in
      the Wisconsin Registry for Alzheimer's Prevention (WRAP).
AB  - Introduction: While it is well known that discourse-related language functions
      are impaired in the dementia phase of Alzheimer's Disease (AD), the
      presymptomatic temporal course of discourse dysfunction are not known earlier in
      the course of AD. To conduct discourse-related studies in this phase of AD,
      validated psychometric instruments are needed. This study investigates the latent
      structure, validity, and test-retest stability of discourse measures in a late
      middle-aged normative group who are relatively free from sporadic AD risk
      factors. Methods: Using a normative sample of 399 participants (mean age = 61),
      exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were
      conducted on 18 measures of connected language derived from picture descriptions.
      Factor invariance across sex and family history and longitudinal test-retest
      stability measures were calculated. Results: The EFA revealed a four-factor
      solution, consisting of semantic, syntax, fluency, and lexical constructs. The
      CFA model substantiated the structure, and factors were invariant across sex and
      parental history of AD status. Test-retest stability measures were within
      acceptable ranges. Conclusions: Results confirm a factor structure that is
      invariant across sex and parental AD history. The factor structure could be
      useful in similar cohorts designed to detect early language decline in
      investigations of preclinical or clinical AD or as outcome measures in clinical
      prevention trials.

PMID- 29186314
TI  - Reproducibility of Retinal Microvascular Traits Decoded by the Singapore I Vessel
      Assessment Software Across the Human Age Range.
AB  - BACKGROUND: Retinal microvascular traits predict adverse health outcomes. The
      Singapore I Vessel Assessment (SIVA) software improved automated postprocessing
      of retinal photographs. In addition to microvessel caliber, it generates measures
      of arteriolar and venular geometry. Few studies addressed the reproducibility of
      SIVA measurements across a wide age range. METHODS: In the current study, 2
      blinded graders read images obtained by nonmydriatic retinal photography twice in
      20 11-year-old children, born prematurely (n = 10) or at term (n = 10) and in 60
      adults (age range, 18.9-86.1 years). RESULTS: Former preterm compared with term
      children had lower microvessel diameter and disorganized vessel geometry with no
      differences in intraobserver and interobserver variability. Among adults,
      microvessel caliber decreased with age and blood pressure and arteriolar geometry
      was inversely correlated with female sex and age. Intraobserver differences
      estimated by the Bland-Altman method did not reach significance for any
      measurement. Across measurements, median reproducibility (RM) expressed as
      percent of the average trait value was 8.8% in children (median intraclass
      correlation coefficient [ICC], 0.94) and 8.0% (0.97) in adults. Likewise,
      interobserver differences did not reach significance with RM (ICC) of 10.6%
      (0.85) in children and 10.4% (0.93) in adults. Reproducibility was best for
      microvessel caliber (intraobserver/interobserver RM, 4.7%/6.0%; ICC, 0.98/0.96),
      worst for venular geometry (17.0%/18.8%; 0.93/0.84), and intermediate for
      arteriolar geometry (10.9%/14.9%; 0.95/0.86). CONCLUSIONS: SIVA produces
      repeatable measures of the retinal microvasculature in former preterm and term
      children and in adults, thereby proving its usability from childhood to old age.

PMID- 29186315
TI  - Resources and tools for the high-throughput, multi-omic study of intestinal
      microbiota.
AB  - The human gut microbiome impacts several aspects of human health and disease,
      including digestion, drug metabolism and the propensity to develop various
      inflammatory, autoimmune and metabolic diseases. Many of the molecular processes
      that play a role in the activity and dynamics of the microbiota go beyond species
      and genic composition and thus, their understanding requires advanced
      bioinformatics support. This article aims to provide an up-to-date view of the
      resources and software tools that are being developed and used in human gut
      microbiome research, in particular data integration and systems-level analysis
      efforts. These efforts demonstrate the power of standardized and reproducible
      computational workflows for integrating and analysing varied omics data and
      gaining deeper insights into microbe community structure and function as well as
      host-microbe interactions.

PMID- 29186316
TI  - A review of databases predicting the effects of SNPs in miRNA genes or miRNA
      binding sites.
AB  - Modern precision medicine comprises the knowledge and understanding of individual
      differences in the genomic sequence of patients to provide tailor-made
      treatments. Regularly, such variants are considered in coding regions only, and
      their effects are predicted based on their impact on the amino acid sequence of
      expressed proteins. However, assessing the effects of variants in noncoding
      elements, in particular microRNAs (miRNAs) and their binding sites, is important
      as well, as a single miRNA can influence the expression patterns of many genes at
      the same time. To analyze the effects of variants in miRNAs and their target
      sites, several databases storing variant impact predictions have been published.
      In this review, we will compare the core functionalities and features of these
      databases and discuss the importance of up-to-date data resources in the context
      of web applications. Finally, we will outline some recommendations for future
      developments in the field.

PMID- 29186317
TI  - Computational profiling of the gut-brain axis: microflora dysbiosis insights to
      neurological disorders.
AB  - Almost 2500 years after Hippocrates' observations on health and its direct
      association to the gastrointestinal tract, a paradigm shift has recently
      occurred, making the gut and its symbionts (bacteria, fungi, archaea and viruses)
      a point of convergence for studies. It is nowadays well established that the gut
      microflora's compositional diversity regulates via its genes (the microbiome) the
      host's health and provides preliminary insights into disease progression and
      regulation. The microbiome's involvement is evident in immunological and
      physiological studies that link changes in its biodiversity to its contributions
      to the host's phenotype but also in neurological investigations, substantiating
      the aptly named gut-brain axis. The definitive mechanisms of this last
      bidirectional interaction will be our main focus because it presents researchers
      with a new conundrum. In this review, we prospect current literature for
      computational analysis methodologies that accommodate the need for better
      understanding of the microbiome-gut-brain interactions and neurological disorder
      onset and progression, through cross-disciplinary systems biology applications.
      We will present bioinformatics tools used in exploring these synergies that help
      build and interpret microbial 16S ribosomal RNA data sets, produced by shotgun
      and high-throughput sequencing of healthy and neurological disorder samples
      stored in biological databases. These approaches provide alternative means for
      researchers to form hypotheses to their inquests faster, cheaper and swith
      precision. The goal of these studies relies on the integration of combined
      metagenomics and metabolomics assessments. An accurate characterization of the
      microbiome and its functionality can support new diagnostic, prognostic and
      therapeutic strategies for neurological disorders, customized for each individual
      host.

PMID- 29186318
TI  - Reply to Nicastri et al.

PMID- 29186319
TI  - OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of
      intraperitoneal versus intravenous chemotherapy following neoadjuvant
      chemotherapy and optimal debulking surgery in epithelial ovarian cancer.
AB  - Background: The purpose of this multistage, adaptively, designed randomized phase
      II study was to evaluate the role of intraperitoneal (i.p.) chemotherapy
      following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women
      with epithelial ovarian cancer (EOC). Patients and methods: We carried out a
      multicenter, two-stage, phase II trial. Eligible patients with stage IIB-IVA EOC
      treated with platinum-based intravenous (i.v.) NACT followed by optimal (<1 cm)
      debulking surgery were randomized to one of the three treatment arms: (i) i.v.
      carboplatin/paclitaxel, (ii) i.p. cisplatin plus i.v./i.p. paclitaxel, or (iii)
      i.p. carboplatin plus i.v./i.p. paclitaxel. The primary end point was 9-month
      progressive disease rate (PD9). Secondary end points included progression-free
      survival (PFS), overall survival (OS), toxicity, and quality of life (QOL).
      Results: Between 2009 and 2015, 275 patients were randomized; i.p. cisplatin
      containing arm did not progress beyond the first stage of the study after failing
      to meet the pre-set superiority rule. The final analysis compared i.v.
      carboplatin/paclitaxel (n = 101) with i.p. carboplatin, i.v./i.p. paclitaxel (n =
      102). The intention to treat PD9 was lower in the i.p. carboplatin arm compared
      with the i.v. carboplatin arm: 24.5% (95% CI 16.2% to 32.9%) versus 38.6% (95% CI
      29.1% to 48.1%) P = 0.065. The study was underpowered to detect differences in
      PFS: HR PFS 0.82 (95% CI 0.57-1.17); P = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) P
      = 0.40. The i.p. carboplatin-based regimen was well tolerated with no reduction
      in QOL or increase in toxicity compared with i.v. administration alone.
      Conclusion: In women with stage IIIC or IVA EOC treated with NACT and optimal
      debulking surgery, i.p. carboplatin-based chemotherapy is well tolerated and
      associated with an improved PD9 compared with i.v. carboplatin-based
      chemotherapy. Clinical trial number: clinicaltrials.gov, NCT01622543.

PMID- 29186321
TI  - Mapping-free variant calling using haplotype reconstruction from k-mer
      frequencies.
AB  - Motivation: The standard protocol for detecting variation in DNA is to map
      millions of short sequence reads to a known reference and find loci that differ.
      While this approach works well, it cannot be applied where the sample contains
      dense variants or is too distant from known references. De novo assembly or
      hybrid methods can recover genomic variation, but the cost of computation is
      often much higher. We developed a novel k-mer algorithm and software
      implementation, Kestrel, capable of characterizing densely packed SNPs and large
      indels without mapping, assembly or de Bruijn graphs. Results: When applied to
      mosaic penicillin binding protein (PBP) genes in Streptococcus pneumoniae, we
      found near perfect concordance with assembled contigs at a fraction of the CPU
      time. Multilocus sequence typing (MLST) with this approach was able to bypass de
      novo assemblies. Kestrel has a very low false-positive rate when applied to the
      whole genome, and while Kestrel identified many variants missed by other methods,
      limitations of a purely k-mer based approach affect overall sensitivity.
      Availability and implementation: Source code and documentation for a Java
      implementation of Kestrel can be found at https://github.com/paudano/kestrel. All
      test code for this publication is located at https://github.com/paudano/kescases.
      Contact: paudano@gatech.edu or fredrik.vannberg@biology.gatech.edu. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29186320
TI  - Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus
      Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy.
AB  - Background: Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV)
      infections in 95% of infected patients. Modeling studies predict that universal
      HCV treatment will lead to a decrease in the incidence of new infections but real
      life data are lacking. The incidence of HCV among Dutch human immunodeficiency
      virus (HIV)-positive men who have sex with men (MSM) has been high for >10 years.
      In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid
      treatment uptake in HIV-positive MSM. We assessed whether this uptake was
      followed by a decrease in the incidence of HCV infections. Methods: Two
      prospective studies of treatment for acute HCV infection enrolled patients in 17
      Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in
      the Netherlands. Patients were recruited in 2014 and 2016, the years before and
      after unrestricted DAA availability. We compared the HCV incidence in both years.
      Results: The incidence of acute HCV infection decreased from 93 infections during
      8290 person-years of follow-up (PYFU) in 2014 (11.2/1000 PYFU; 95% confidence
      interval [CI], 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1-7.2).
      The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35-.69).
      Simultaneously, a significant increase in the percentage positive syphilis
      (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual
      health clinics across the Netherlands and contradicts a decrease in risk behavior
      as an alternative explanation. Conclusions: Unrestricted DAA availability in the
      Netherlands was followed by a 51% decrease in acute HCV infections among HIV
      positive MSM.

PMID- 29186322
TI  - SAPP: functional genome annotation and analysis through a semantic framework
      using FAIR principles.
AB  - Summary: To unlock the full potential of genome data and to enhance data
      interoperability and reusability of genome annotations we have developed SAPP, a
      Semantic Annotation Platform with Provenance. SAPP is designed as an
      infrastructure supporting FAIR de novo computational genomics but can also be
      used to process and analyze existing genome annotations. SAPP automatically
      predicts, tracks and stores structural and functional annotations and associated
      dataset- and element-wise provenance in a Linked Data format, thereby enabling
      information mining and retrieval with Semantic Web technologies. This greatly
      reduces the administrative burden of handling multiple analysis tools and
      versions thereof and facilitates multi-level large scale comparative analysis.
      Availability and implementation: SAPP is written in JAVA and freely available at
      https://gitlab.com/sapp and runs on Unix-like operating systems. The
      documentation, examples and a tutorial are available at https://sapp.gitlab.io.
      Contact: jasperkoehorst@gmail.com or peter.schaap@wur.nl.

PMID- 29186323
TI  - An attention-based BiLSTM-CRF approach to document-level chemical named entity
      recognition.
AB  - Motivation: In biomedical research, chemical is an important class of entities,
      and chemical named entity recognition (NER) is an important task in the field of
      biomedical information extraction. However, most popular chemical NER methods are
      based on traditional machine learning and their performances are heavily
      dependent on the feature engineering. Moreover, these methods are sentence-level
      ones which have the tagging inconsistency problem. Results: In this paper, we
      propose a neural network approach, i.e. attention-based bidirectional Long Short
      Term Memory with a conditional random field layer (Att-BiLSTM-CRF), to document
      level chemical NER. The approach leverages document-level global information
      obtained by attention mechanism to enforce tagging consistency across multiple
      instances of the same token in a document. It achieves better performances with
      little feature engineering than other state-of-the-art methods on the BioCreative
      IV chemical compound and drug name recognition (CHEMDNER) corpus and the
      BioCreative V chemical-disease relation (CDR) task corpus (the F-scores of 91.14
      and 92.57%, respectively). Availability and implementation: Data and code are
      available at https://github.com/lingluodlut/Att-ChemdNER. Contact:
      yangzh@dlut.edu.cn or wangleibihami@gmail.com. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29186324
TI  - Robust inference of population structure from next-generation sequencing data
      with systematic differences in sequencing.
AB  - Motivation: Inferring population structure is important for both population
      genetics and genetic epidemiology. Principal components analysis (PCA) has been
      effective in ascertaining population structure with array genotype data but can
      be difficult to use with sequencing data, especially when low depth leads to
      uncertainty in called genotypes. Because PCA is sensitive to differences in
      variability, PCA using sequencing data can result in components that correspond
      to differences in sequencing quality (read depth and error rate), rather than
      differences in population structure. We demonstrate that even existing methods
      for PCA specifically designed for sequencing data can still yield biased
      conclusions when used with data having sequencing properties that are
      systematically different across different groups of samples (i.e. sequencing
      groups). This situation can arise in population genetics when combining
      sequencing data from different studies, or in genetic epidemiology when using
      historical controls such as samples from the 1000 Genomes Project. Results: To
      allow inference on population structure using PCA in these situations, we provide
      an approach that is based on using sequencing reads directly without calling
      genotypes. Our approach is to adjust the data from different sequencing groups to
      have the same read depth and error rate so that PCA does not generate spurious
      components representing sequencing quality. To accomplish this, we have developed
      a subsampling procedure to match the depth distributions in different sequencing
      groups, and a read-flipping procedure to match the error rates. We average over
      subsamples and read flips to minimize loss of information. We demonstrate the
      utility of our approach using two datasets from 1000 Genomes, and further
      evaluate it using simulation studies. Availability and implementation: TASER-PC
      software is publicly available at
      http://web1.sph.emory.edu/users/yhu30/software.html. Contact:
      yijuan.hu@emory.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29186325
TI  - glactools: a command-line toolset for the management of genotype likelihoods and
      allele counts.
AB  - Motivation: Research projects involving population genomics routinely need to
      store genotyping information, population allele counts, combine files from
      different samples, query the data and export it to various formats. This is often
      done using bespoke in-house scripts, which cannot be easily adapted to new
      projects and seldom constitute reproducible workflows. Results: We introduce
      glactools, a set of command-line utilities that can import data from genotypes or
      population-wide allele counts into an intermediate representation, compute
      various operations on it and export the data to several file formats used by
      population genetics software. This intermediate format can take two forms, one to
      store per-individual genotype likelihoods and a second for allele counts from one
      or more individuals. glactools allows users to perform operations such as
      intersecting datasets, merging individuals into populations, creating subsets,
      perform queries (e.g. return sites where a given population does not share an
      allele with a second one) and compute summary statistics to answer biologically
      relevant questions. Availability and implementation: glactools is freely
      available for use under the GPL. It requires a C ++ compiler and the htslib
      library. The source code and the instructions about how to download test data are
      available on the website (https://grenaud.github.io/glactools/). Contact:
      gabriel.reno@gmail.com. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29186326
TI  - Is Hepatitis C Virus Elimination in Well-Defined Patient Groups Possible?

PMID- 29186327
TI  - Efficiently counting all orbits of graphlets of any order in a graph using
      autogenerated equations.
AB  - Motivation: Graphlets are a useful tool to determine a graph's small-scale
      structure. Finding them is exponentially hard with respect to the number of nodes
      in each graphlet. Therefore, equations can be used to reduce the size of
      graphlets that need to be enumerated to calculate the number of each graphlet
      touching each node. Hocevar and Demsar first introduced such equations, which
      were derived manually, and an algorithm that uses them, but only graphlets with
      four or five nodes can be counted this way. Results: We present a new algorithm
      for orbit counting, which is applicable to graphlets of any order. This algorithm
      uses a tree structure to simplify finding orbits, and stabilizers and symmetry
      breaking constraints to ensure correctness. This method gives a significant
      speedup compared to a brute force counting method and can count orbits beyond the
      capacity of other available tools. Availability and implementation: An
      implementation of the algorithm can be found at
      https://github.com/biointec/jesse. Contact: pieter.audenaert@ugent.be.

PMID- 29186328
TI  - Meta-analytic principal component analysis in integrative omics application.
AB  - Motivation: With the prevalent usage of microarray and massively parallel
      sequencing, numerous high-throughput omics datasets have become available in the
      public domain. Integrating abundant information among omics datasets is critical
      to elucidate biological mechanisms. Due to the high-dimensional nature of the
      data, methods such as principal component analysis (PCA) have been widely
      applied, aiming at effective dimension reduction and exploratory visualization.
      Results: In this article, we combine multiple omics datasets of identical or
      similar biological hypothesis and introduce two variations of meta-analytic
      framework of PCA, namely MetaPCA. Regularization is further incorporated to
      facilitate sparse feature selection in MetaPCA. We apply MetaPCA and sparse
      MetaPCA to simulations, three transcriptomic meta-analysis studies in yeast cell
      cycle, prostate cancer, mouse metabolism and a TCGA pan-cancer methylation study.
      The result shows improved accuracy, robustness and exploratory visualization of
      the proposed framework. Availability and implementation: An R package MetaPCA is
      available online. (http://tsenglab.biostat.pitt.edu/software.htm). Contact:
      ctseng@pitt.edu. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29186329
TI  - ASElux: an ultra-fast and accurate allelic reads counter.
AB  - Motivation: Mapping bias causes preferential alignment to the reference allele,
      forming a major obstacle in allele-specific expression (ASE) analysis. The
      existing methods, such as simulation and SNP-aware alignment, are either
      inaccurate or relatively slow. To fast and accurately count allelic reads for ASE
      analysis, we developed a novel approach, ASElux, which utilizes the personal SNP
      information and counts allelic reads directly from unmapped RNA-sequence (RNA
      seq) data. ASElux significantly reduces runtime by disregarding reads outside
      single nucleotide polymorphisms (SNPs) during the alignment. Results: When
      compared to other tools on simulated and experimental data, ASElux achieves a
      higher accuracy on ASE estimation than non-SNP-aware aligners and requires a much
      shorter time than the benchmark SNP-aware aligner, GSNAP with just a slight loss
      in performance. ASElux can process 40 million read-pairs from an RNA-sequence
      (RNA-seq) sample and count allelic reads within 10 min, which is comparable to
      directly counting the allelic reads from alignments based on other tools.
      Furthermore, processing an RNA-seq sample using ASElux in conjunction with a
      general aligner, such as STAR, is more accurate and still ~4* faster than STAR +
      WASP, and ~33* faster than the lead SNP-aware aligner, GSNAP, making ASElux ideal
      for ASE analysis of large-scale transcriptomic studies. We applied ASElux to 273
      lung RNA-seq samples from GTEx and identified a splice-QTL rs11078928 in lung
      which explains the mechanism underlying an asthma GWAS SNP rs11078927. Thus, our
      analysis demonstrated ASE as a highly powerful complementary tool to cis
      expression quantitative trait locus (eQTL) analysis. Availability and
      implementation: The software can be downloaded from
      https://github.com/abl0719/ASElux. Contact: zmiao@ucla.edu or a5ko@ucla.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29186330
TI  - Utilization of a clinical microbiology service at a Cambodian paediatric hospital
      and its impact on appropriate antimicrobial prescribing.
AB  - Background: Antimicrobial resistance threatens human health worldwide.
      Antimicrobial misuse is a major driver of resistance. Promoting appropriate
      antimicrobial use requires an understanding of how clinical microbiology services
      are utilized, particularly in resource-limited settings. Objectives: To assess
      the appropriateness of antimicrobial prescribing and the factors affecting
      utilization of the established clinical microbiology service (CMS). The CMS
      comprises the microbiology laboratory, clinical microbiologists (infection
      doctors) and antimicrobial treatment guidelines. Methods: This mixed-methods
      study was conducted at a non-governmental Cambodian paediatric hospital.
      Empirical and post-culture antimicrobial prescriptions were reviewed from medical
      records. The random sample included 10 outpatients per week in 2016
      (retrospective) and 20 inpatients per week for 4 weeks in the medical, neonatal
      and intensive care wards (prospective). Post-culture prescriptions were assessed
      in patients with positive blood and cerebrospinal fluid cultures from 1 January
      2014 to 31 December 2016. Focus group discussions and semi-structured interviews
      with clinicians explored barriers and facilitators to use of the CMS. Results:
      Only 31% of outpatients were prescribed empirical antimicrobials. Post-culture
      prescriptions (394/443, 89%) were more likely to be appropriate than empirical
      prescriptions (447/535, 84%), based on treatment guidelines, microbiology advice
      and antimicrobial susceptibility test results (P = 0.015). Being comprehensive,
      accessible and trusted enabled CMS utilization. Clinical microbiologists provided
      a crucial human interface between the CMS and physicians. The main barriers were
      a strong clinical hierarchy and occasional communication difficulties.
      Conclusions: Antimicrobial prescribing in this hospital was largely appropriate.
      A culturally appropriate human interface linking the laboratory and physicians is
      essential in providing effective microbiology services and ensuring appropriate
      antimicrobial prescribing in resource-limited settings.

PMID- 29186332
TI  - The systematic analysis of ultraconserved genomic regions in the budding yeast.

PMID- 29186333
TI  - FUn: a framework for interactive visualizations of large, high-dimensional
      datasets on the web.
AB  - Motivation: During the past decade, big data have become a major tool in
      scientific endeavors. Although statistical methods and algorithms are well-suited
      for analyzing and summarizing enormous amounts of data, the results do not allow
      for a visual inspection of the entire data. Current scientific software,
      including R packages and Python libraries such as ggplot2, matplotlib and
      plot.ly, do not support interactive visualizations of datasets exceeding 100 000
      data points on the web. Other solutions enable the web-based visualization of big
      data only through data reduction or statistical representations. However, recent
      hardware developments, especially advancements in graphical processing units,
      allow for the rendering of millions of data points on a wide range of consumer
      hardware such as laptops, tablets and mobile phones. Similar to the challenges
      and opportunities brought to virtually every scientific field by big data, both
      the visualization of and interaction with copious amounts of data are both
      demanding and hold great promise. Results: Here we present FUn, a framework
      consisting of a client (Faerun) and server (Underdark) module, facilitating the
      creation of web-based, interactive 3D visualizations of large datasets, enabling
      record level visual inspection. We also introduce a reference implementation
      providing access to SureChEMBL, a database containing patent information on more
      than 17 million chemical compounds. Availability and implementation: The source
      code and the most recent builds of Faerun and Underdark, Lore.js and the data
      preprocessing toolchain used in the reference implementation, are available on
      the project website (http://doc.gdb.tools/fun/). Contact:
      daniel.probst@dcb.unibe.ch or jean-louis.reymond@dcb.unibe.ch.

PMID- 29186331
TI  - DDR: efficient computational method to predict drug-target interactions using
      graph mining and machine learning approaches.
AB  - Motivation: Finding computationally drug-target interactions (DTIs) is a
      convenient strategy to identify new DTIs at low cost with reasonable accuracy.
      However, the current DTI prediction methods suffer the high false positive
      prediction rate. Results: We developed DDR, a novel method that improves the DTI
      prediction accuracy. DDR is based on the use of a heterogeneous graph that
      contains known DTIs with multiple similarities between drugs and multiple
      similarities between target proteins. DDR applies non-linear similarity fusion
      method to combine different similarities. Before fusion, DDR performs a pre
      processing step where a subset of similarities is selected in a heuristic process
      to obtain an optimized combination of similarities. Then, DDR applies a random
      forest model using different graph-based features extracted from the DTI
      heterogeneous graph. Using 5-repeats of 10-fold cross-validation, three testing
      setups, and the weighted average of area under the precision-recall curve (AUPR)
      scores, we show that DDR significantly reduces the AUPR score error relative to
      the next best start-of-the-art method for predicting DTIs by 34% when the drugs
      are new, by 23% when targets are new and by 34% when the drugs and the targets
      are known but not all DTIs between them are not known. Using independent sources
      of evidence, we verify as correct 22 out of the top 25 DDR novel predictions.
      This suggests that DDR can be used as an efficient method to identify correct
      DTIs. Availability and implementation: The data and code are provided at
      https://bitbucket.org/RSO24/ddr/. Contact: vladimir.bajic@kaust.edu.sa.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29186334
TI  - Phenotypic stability and plasticity in GMP-derived cells as determined by their
      underlying regulatory network.
AB  - Motivation: Blood cell formation has been recognized as a suitable system to
      study celular differentiation mainly because of its experimental accessibility,
      and because it shows characteristics such as hierarchical and gradual bifurcated
      patterns of commitment, which are present in several developmental processes.
      Although hematopoiesis has been extensively studied and there is a wealth of
      molecular and cellular data about it, it is not clear how the underlying
      molecular regulatory networks define or restrict cellular differentiation
      processes. Here, we infer the molecular regulatory network that controls the
      differentiation of a blood cell subpopulation derived from the granulocyte
      monocyte precursor (GMP), comprising monocytes, neutrophils, eosinophils,
      basophils and mast cells. Results: We integrate published qualitative
      experimental data into a model to describe temporal expression patterns observed
      in GMP-derived cells. The model is implemented as a Boolean network, and its
      dynamical behavior is studied. Steady states of the network can be clearly
      identified with the expression profiles of monocytes, mast cells, neutrophils,
      basophils, and eosinophils, under wild-type and mutant backgrounds. Availability
      and implementation: All scripts are publicly available at
      https://github.com/caramirezal/RegulatoryNetworkGMPModel. Contact:
      lmendoza@biomedicas.unam.mx. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29186336
TI  - 3dRPC: a web server for 3D RNA-protein structure prediction.
AB  - : RNA-protein interactions occur in many biological processes. To understand the
      mechanism of these interactions one needs to know three-dimensional (3D)
      structures of RNA-protein complexes. 3dRPC is an algorithm for prediction of 3D
      RNA-protein complex structures and consists of a docking algorithm RPDOCK and a
      scoring function 3dRPC-Score. RPDOCK is used to sample possible complex
      conformations of an RNA and a protein by calculating the geometric and
      electrostatic complementarities and stacking interactions at the RNA-protein
      interface according to the features of atom packing of the interface. 3dRPC-Score
      is a knowledge-based potential that uses the conformations of nucleotide-amino
      acid pairs as statistical variables and that is used to choose the near-native
      complex-conformations obtained from the docking method above. Recently, we built
      a web server for 3dRPC. The users can easily use 3dRPC without installing it
      locally. RNA and protein structures in PDB (Protein Data Bank) format are the
      only needed input files. It can also incorporate the information of interface
      residues or residue-pairs obtained from experiments or theoretical predictions to
      improve the prediction. Availability and implementation: The address of 3dRPC web
      server is http://biophy.hust.edu.cn/3dRPC. Contact: yxiao@hust.edu.cn.

PMID- 29186335
TI  - The OncoPPi Portal: an integrative resource to explore and prioritize protein
      protein interactions for cancer target discovery.
AB  - Motivation: As cancer genomics initiatives move toward comprehensive
      identification of genetic alterations in cancer, attention is now turning to
      understanding how interactions among these genes lead to the acquisition of tumor
      hallmarks. Emerging pharmacological and clinical data suggest a highly promising
      role of cancer-specific protein-protein interactions (PPIs) as druggable cancer
      targets. However, large-scale experimental identification of cancer-related PPIs
      remains challenging, and currently available resources to explore oncogenic PPI
      networks are limited. Results: Recently, we have developed a PPI high-throughput
      screening platform to detect PPIs between cancer-associated proteins in the
      context of cancer cells. Here, we present the OncoPPi Portal, an interactive web
      resource that allows investigators to access, manipulate and interpret a high
      quality cancer-focused network of PPIs experimentally detected in cancer cell
      lines. To facilitate prioritization of PPIs for further biological studies, this
      resource combines network connectivity analysis, mutual exclusivity analysis of
      genomic alterations, cellular co-localization of interacting proteins and domain
      domain interactions. Estimates of PPI essentiality allow users to evaluate the
      functional impact of PPI disruption on cancer cell proliferation. Furthermore,
      connecting the OncoPPi network with the approved drugs and compounds in clinical
      trials enables discovery of new tumor dependencies to inform strategies to
      interrogate undruggable targets like tumor suppressors. The OncoPPi Portal serves
      as a resource for the cancer research community to facilitate discovery of cancer
      targets and therapeutic development. Availability and implementation: The OncoPPi
      Portal is available at http://oncoppi.emory.edu. Contact: andrey.ivanov@emory.edu
      or hfu@emory.edu.

PMID- 29186337
TI  - CytoCtrlAnalyser: a Cytoscape app for biomolecular network controllability
      analysis.
AB  - Summary: Studying the controllability of biomolecular networks can result in
      profound knowledge about molecular biological systems. However, there is no
      comprehensive and easy-to-use platform for analyzing controllability of
      biomolecular networks although various algorithms for analyzing complex network
      controllability have been proposed recently. In this application note, we develop
      the CytoCtrlAnalyser which is a Cytoscape app to provide a comprehensive platform
      for analyzing controllability of biomolecular networks. Nine algorithms have been
      integrated in CytoCtrlAnalyser. With network topologies and customized control
      settings imported into CytoCtrlAnalyser, users can identify the steering nodes
      which should be actuated by input control signals for achieving different control
      objectives as well as investigate the importance of nodes from different
      perspectives in the controllability of networks. CytoCtrlAnalyser offers a tool
      for many promising applications, such as identification of potential drug targets
      or biologically important nodes in biomolecular networks. Availability and
      implementation: Freely available for downloading at
      http://apps.cytoscape.org/apps/cytoctrlanalyser. Contact: faw341@mail.usask.ca.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29186338
TI  - Cpf1-Database: web-based genome-wide guide RNA library design for gene knockout
      screens using CRISPR-Cpf1.
AB  - Summary: Following the type II CRISPR-Cas9 system, type V CRISPR-Cpf1
      endonucleases have been found to be applicable for genome editing in various
      organisms in vivo. However, there are as yet no web-based tools capable of
      optimally selecting guide RNAs (gRNAs) among all possible genome-wide target
      sites. Here, we present Cpf1-Database, a genome-wide gRNA library design tool for
      LbCpf1 and AsCpf1, which have DNA recognition sequences of 5'-TTTN-3' at the 5'
      ends of target sites. Cpf1-Database provides a sophisticated but simple way to
      design gRNAs for AsCpf1 nucleases on the genome scale. One can easily access the
      data using a straightforward web interface, and using the powerful collections
      feature one can easily design gRNAs for thousands of genes in short time.
      Availability and implementation: Free access at http://www.rgenome.net/cpf1
      database/. Contact: sangsubae@hanyang.ac.kr.

PMID- 29186339
TI  - bioalcidae, samjs and vcffilterjs: object-oriented formatters and filters for
      bioinformatics files.
AB  - Motivation: Reformatting and filtering bioinformatics files are common tasks for
      bioinformaticians. Standard Linux tools and specific programs are usually used to
      perform such tasks but there is still a gap between using these tools and the
      programming interface of some existing libraries. Results: In this study, we
      developed a set of tools namely bioalcidae, samjs and vcffilterjs that reformat
      or filter files using a JavaScript engine or a pure java expression and taking
      advantage of the java API for high-throughput sequencing data (htsjdk).
      Availability and implementation: https://github.com/lindenb/jvarkit. Contact:
      pierre.lindenbaum@univ-nantes.fr.

PMID- 29186340
TI  - Semi-supervised network inference using simulated gene expression dynamics.
AB  - Motivation: Inferring the structure of gene regulatory networks from high
      throughput datasets remains an important and unsolved problem. Current methods
      are hampered by problems such as noise, low sample size, and incomplete
      characterizations of regulatory dynamics, leading to networks with missing and
      anomalous links. Integration of prior network information (e.g. from pathway
      databases) has the potential to improve reconstructions. Results: We developed a
      semi-supervised network reconstruction algorithm that enables the synthesis of
      information from partially known networks with time course gene expression data.
      We adapted partial least square-variable importance in projection (VIP) for time
      course data and used reference networks to simulate expression data from which
      null distributions of VIP scores are generated and used to estimate edge
      probabilities for input expression data. By using simulated dynamics to generate
      reference distributions, this approach incorporates previously known regulatory
      relationships and links the network to the dynamics to form a semi-supervised
      approach that discovers novel and anomalous connections. We applied this approach
      to data from a sleep deprivation study with KEGG pathways treated as prior
      networks, as well as to synthetic data from several DREAM challenges, and find
      that it is able to recover many of the true edges and identify errors in these
      networks, suggesting its ability to derive posterior networks that accurately
      reflect gene expression dynamics. Availability and implementation: R code is
      available at https://github.com/pn51/postPLSR. Contact: rbraun@northwestern.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29186341
TI  - Invasive Fungal Sinusitis due to Mucor Species in a Patient on Ibrutinib.

PMID- 29186342
TI  - Linking Metabolic Disease With the PGC-1alpha Gly482Ser Polymorphism.
AB  - Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha)
      is a highly conserved transcriptional coactivator enriched in metabolically
      active tissues including liver, adipose, pancreas, and muscle. It plays a role in
      regulating whole body energy metabolism and its deregulation has been implicated
      in type 2 diabetes (T2D). A single nucleotide variant of the PPARGC1A gene
      (rs8192678) is associated with T2D susceptibility, relative risk of obesity and
      insulin resistance, and lower indices of beta cell function. This common
      polymorphism is within a highly conserved region of the bioactive protein and
      leads to a single amino acid substitution (glycine 482 to serine). Its prevalence
      and effects on metabolic parameters appear to vary depending on factors including
      ethnicity and sex, suggesting important interactions between genetics and
      cultural/environmental factors and associated disease risk. Interestingly,
      carriers of the serine allele respond better to some T2D interventions,
      illustrating the importance of understanding functional impacts of genetic
      variance on PGC-1alpha when targeting this pathway for personalized medicine.
      This review summarizes a growing body of literature surrounding possible links
      between the PGC-1alpha Gly482Ser single nucleotide polymorphism and diabetes,
      with focus on key clinical findings, affected metabolic systems, potential
      molecular mechanisms, and the influence of geographical or ethnic background on
      associated risk.

PMID- 29186344
TI  - MOCASSIN-prot: a multi-objective clustering approach for protein similarity
      networks.
AB  - Motivation: Proteins often include multiple conserved domains. Various
      evolutionary events including duplication and loss of domains, domain shuffling,
      as well as sequence divergence contribute to generating complexities in protein
      structures, and consequently, in their functions. The evolutionary history of
      proteins is hence best modeled through networks that incorporate information both
      from the sequence divergence and the domain content. Here, a game-theoretic
      approach proposed for protein network construction is adapted into the framework
      of multi-objective optimization, and extended to incorporate clustering
      refinement procedure. Results: The new method, MOCASSIN-prot, was applied to
      cluster multi-domain proteins from ten genomes. The performance of MOCASSIN-prot
      was compared against two protein clustering methods, Markov clustering (TRIBE
      MCL) and spectral clustering (SCPS). We showed that compared to these two
      methods, MOCASSIN-prot, which uses both domain composition and quantitative
      sequence similarity information, generates fewer false positives. It achieves
      more functionally coherent protein clusters and better differentiates protein
      families. Availability and implementation: MOCASSIN-prot, implemented in Perl and
      Matlab, is freely available at http://bioinfolab.unl.edu/emlab/MOCASSINprot.
      Contact: emoriyama2@unl.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29186343
TI  - Relative contributions of neutral and non-neutral processes to clinal variation
      in calyx lobe length in the series Sakawanum (Asarum: Aristolochiaceae).
AB  - Background and Aims: Clines, the gradual variation in measurable traits along a
      geographical axis, play a major role in evolution and can contribute to our
      understanding of the relative roles of selective and neutral process in trait
      variation. Using genetic and morphological analyses, the relative contributions
      of neutral and non-neutral processes were explored to infer the evolutionary
      history of species of the series Sakawanum (genus Asarum), which shows
      significant clinal variation in calyx lobe length. Methods: A total of 27
      populations covering the natural geographical distribution of the series
      Sakawanum were sampled. Six nuclear microsatellite markers were used to
      investigate genetic structure and genetic diversity. The lengths of calyx lobes
      of multiple populations were measured to quantify their geographical and
      taxonomic differentiation. To detect the potential impact of selective pressure,
      morphological differentiation was compared with genetic differentiation (QCT-FST
      comparison). Key Results: Average calyx lobe length of A. minamitanianum was
      124.11 mm, while that of A. costatum was 13.80 mm. Though gradually changing
      along the geographical axis within series, calyx lobe lengths were significantly
      differentiated among the taxa. Genetic differentiation between taxa was low (FST
      = 0.099), but a significant geographical structure along the morphological cline
      was detected. Except for one taxon pair, pairwise QCT values were significantly
      higher than the neutral genetic measures of FST and G'ST. Conclusions: Divergent
      selection may have driven the calyx lobe length variation in series Sakawanum
      taxa, although the underlying mechanism is still not clear. The low genetic
      differentiation indicates recent divergence and/or gene flows between
      geographically close taxa. These neutral processes would also affect the clinal
      variation in calyx lobe lengths. Overall, this study implies the roles of
      population history and divergent selection in shaping the current cline of a
      flower trait in the series Sakawanum.

PMID- 29186345
TI  - Organizational Principles of Abstract Words in the Human Brain.
AB  - words constitute nearly half of the human lexicon and are critically associated
      with human abstract thoughts, yet little is known about how they are represented
      in the brain. We tested the neural basis of 2 classical cognitive notions of
      abstract meaning representation: by linguistic contexts and by semantic features.
      We collected fMRI BOLD responses for 360 abstract words and built theoretical
      representational models from state-of-the-art corpus-based natural language
      processing models and behavioral ratings of semantic features. Representational
      similarity analyses revealed that both linguistic contextual and semantic feature
      similarity affected the representation of abstract concepts, but in distinct
      neural levels. The corpus-based similarity was coded in the high-level linguistic
      processing system, whereas semantic feature information was reflected in
      distributed brain regions and in the principal component space derived from whole
      brain activation patterns. These findings highlight the multidimensional
      organization and the neural dissociation between linguistic contextual and
      featural aspects of abstract concepts.

PMID- 29186346
TI  - Pharmacokinetic Assessments of Liquiritin, Protocatechuic Aldehyde and Rosmarinic
      Acid in Rat Plasma by UPLC-MS-MS After Administration of ZibuPiyin Recipe.
AB  - The three analytes of the Traditional Chinese Medicine ZibuPiyin Recipe (ZBPYR),
      namely, liquiritin, protocatechuic aldehyde and rosmarinic acid, may
      synergistically play an important role in regulating memory and learning.
      However, the pharmacokinetic behaviors of these compounds after their co
      administration remain unclear. To this end, a selective and sensitive ultra
      performance liquid chromatography-tandem mass spectrometry method was developed
      and validated in rat plasma for the study of these three major bioactive
      ingredients in ZBPYR. The analytes in the plasma samples were separated on a
      Shiseido Capcell core C18 column using bendrofluazide as an internal standard,
      with a gradient mobile phase system of acetonitrile-water containing 0.1% formic
      acid. Electrospray ionization in the negative-ion mode and multiple reaction
      monitoring were used to identify and quantify the three analytes. All of the
      calibration curves showed good linearity (r > 0.992) over the concentration
      range, with a lower limit of quantification of 5 ng/mL. The precision of the
      analytical method was evaluated by intra- and inter-day assays, and the
      percentage of relative standard deviation (SD) was within 15%. Satisfactory
      extraction efficiency (between 83.4 and 99.4%) and matrix effects (76.4-107.4)
      were obtained by liquid-liquid extraction. The pharmacokinetic results showed
      that the three bioactive ingredients were rapidly absorbed and had a short
      terminal half-life in rats after oral administration of ZibuPiyin recipe. This
      UPLC-MS-MS study method used in this study may be useful for assessing the
      pharmacokinetic characteristics of various compounds, which would be helpful in
      determining their clinical potential.

PMID- 29186347
TI  - Severe Respiratory Illness Associated With Rhinovirus During the Enterovirus D68
      Outbreak in the United States, August 2014-November 2014.
AB  - Background: In 2014, a nationwide outbreak of severe respiratory illness occurred
      in the United States, primarily associated with enterovirus D68 (EV-D68). A
      proportion of illness was associated with rhinoviruses (RVs) and other
      enteroviruses (EVs), which we aimed to characterize further. Methods: Respiratory
      specimens from pediatric and adult patients with respiratory illness were
      submitted to the Centers for Disease Control and Prevention during August 2014
      November 2014. While initial laboratory testing focused on identification of EV
      D68, the negative specimens were typed by molecular sequencing to identify
      additional EV and RV types. Testing for other pathogens was not conducted. We
      compared available clinical and epidemiologic characteristics among patients with
      EV-D68 and RV species A-C identified. Results: Among 2629 typed specimens, 1012
      were EV-D68 (39%) and 81 (3.1%) represented 24 other EV types; 968 were RVs (37%)
      covering 114 types and grouped into 3 human RV species (RV-A, 446; RV-B, 133; RV
      C, 389); and 568 (22%) had no RV or EV detected. EV-D68 was more frequently
      identified in patients who presented earlier in the investigation period. Among
      patients with EV-D68, RV-A, RV-B, or RV-C, the age distributions markedly
      differed. Clinical syndromes and intensive care unit admissions by age were
      largely similar. Conclusions: RVs were commonly associated with severe
      respiratory illness during a nationwide outbreak of EV-D68, and most clinical.
      Characteristics were similar between groups. A better understanding of the
      epidemiology of RVs and EVs is needed to help inform development and use of
      diagnostic tests, therapeutics, and preventive measures.

PMID- 29186348
TI  - Spiking Suppression Precedes Cued Attentional Enhancement of Neural Responses in
      Primary Visual Cortex.
AB  - Attending to a visual stimulus increases its detectability, even if gaze is
      directed elsewhere. This covert attentional selection is known to enhance spiking
      across many brain areas, including the primary visual cortex (V1). Here we
      investigate the temporal dynamics of attention-related spiking changes in V1 of
      macaques performing a task that separates attentional selection from the onset of
      visual stimulation. We found that preceding attentional enhancement there was a
      sharp, transient decline in spiking following presentation of an attention
      guiding cue. This disruption of V1 spiking was not observed in a task-naive
      subject that passively observed the same stimulus sequence, suggesting that
      sensory activation is insufficient to cause suppression. Following this
      suppression, attended stimuli evoked more spiking than unattended stimuli,
      matching previous reports of attention-related activity in V1. Laminar analyses
      revealed a distinct pattern of activation in feedback-associated layers during
      both the cue-induced suppression and subsequent attentional enhancement. These
      findings suggest that top-down modulation of V1 spiking can be bidirectional and
      result in either suppression or enhancement of spiking responses.

PMID- 29186349
TI  - GDSCTools for mining pharmacogenomic interactions in cancer.
AB  - Motivation: Large pharmacogenomic screenings integrate heterogeneous cancer
      genomic datasets as well as anti-cancer drug responses on thousand human cancer
      cell lines. Mining this data to identify new therapies for cancer sub-populations
      would benefit from common data structures, modular computational biology tools
      and user-friendly interfaces. Results: We have developed GDSCTools: a software
      aimed at the identification of clinically relevant genomic markers of drug
      response. The Genomics of Drug Sensitivity in Cancer (GDSC) database
      (www.cancerRxgene.org) integrates heterogeneous cancer genomic datasets as well
      as anti-cancer drug responses on a thousand cancer cell lines. Including
      statistical tools (analysis of variance) and predictive methods (Elastic Net), as
      well as common data structures, GDSCTools allows users to reproduce published
      results from GDSC and to implement new analytical methods. In addition, non-GDSC
      data resources can also be analysed since drug responses and genomic features can
      be encoded as CSV files. Contact: thomas.cokelaer@pasteur.fr or
      saezrodriguez.rwth-aachen.de or mg12@sanger.ac.uk. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29186350
TI  - Macrophage enzyme and reduced inflammation drive brain correction of
      mucopolysaccharidosis IIIB by stem cell gene therapy.
AB  - Mucopolysaccharidosis IIIB is a paediatric lysosomal storage disease caused by
      deficiency of the enzyme alpha-N-acetylglucosaminidase (NAGLU), involved in the
      degradation of the glycosaminoglycan heparan sulphate. Absence of NAGLU leads to
      accumulation of partially degraded heparan sulphate within lysosomes and the
      extracellular matrix, giving rise to severe CNS degeneration with progressive
      cognitive impairment and behavioural problems. There are no therapies.
      Haematopoietic stem cell transplant shows great efficacy in the related disease
      mucopolysaccharidosis I, where donor-derived monocytes can transmigrate into the
      brain following bone marrow engraftment, secrete the missing enzyme and cross
      correct neighbouring cells. However, little neurological correction is achieved
      in patients with mucopolysaccharidosis IIIB. We have therefore developed an ex
      vivo haematopoietic stem cell gene therapy approach in a mouse model of
      mucopolysaccharidosis IIIB, using a high-titre lentiviral vector and the myeloid
      specific CD11b promoter, driving the expression of NAGLU (LV.NAGLU). To
      understand the mechanism of correction we also compared this with a poorly
      secreted version of NAGLU containing a C-terminal fusion to IGFII (LV.NAGLU
      IGFII). Mucopolysaccharidosis IIIB haematopoietic stem cells were transduced with
      vector, transplanted into myeloablated mucopolysaccharidosis IIIB mice and
      compared at 8 months of age with mice receiving a wild-type transplant. As the
      disease is characterized by increased inflammation, we also tested the anti
      inflammatory steroidal agent prednisolone alone, or in combination with LV.NAGLU,
      to understand the importance of inflammation on behaviour. NAGLU enzyme was
      substantially increased in the brain of LV.NAGLU and LV.NAGLU-IGFII-treated mice,
      with little expression in wild-type bone marrow transplanted mice. LV.NAGLU
      treatment led to behavioural correction, normalization of heparan sulphate and
      sulphation patterning, reduced inflammatory cytokine expression and correction of
      astrocytosis, microgliosis and lysosomal compartment size throughout the brain.
      The addition of prednisolone improved inflammatory aspects further. Substantial
      correction of lysosomal storage in neurons and astrocytes was also achieved in
      LV.NAGLU-IGFII-treated mice, despite limited enzyme secretion from engrafted
      macrophages in the brain. Interestingly both wild-type bone marrow transplant and
      prednisolone treatment alone corrected behaviour, despite having little effect on
      brain neuropathology. This was attributed to a decrease in peripheral
      inflammatory cytokines. Here we show significant neurological disease correction
      is achieved using haematopoietic stem cell gene therapy, suggesting this therapy
      alone or in combination with anti-inflammatories may improve neurological
      function in patients.

PMID- 29186351
TI  - Reactome diagram viewer: data structures and strategies to boost performance.
AB  - Motivation: Reactome is a free, open-source, open-data, curated and peer-reviewed
      knowledgebase of biomolecular pathways. For web-based pathway visualization,
      Reactome uses a custom pathway diagram viewer that has been evolved over the past
      years. Here, we present comprehensive enhancements in usability and performance
      based on extensive usability testing sessions and technology developments, aiming
      to optimize the viewer towards the needs of the community. Results: The pathway
      diagram viewer version 3 achieves consistently better performance, loading and
      rendering of 97% of the diagrams in Reactome in less than 1 s. Combining the
      multi-layer html5 canvas strategy with a space partitioning data structure
      minimizes CPU workload, enabling the introduction of new features that further
      enhance user experience. Through the use of highly optimized data structures and
      algorithms, Reactome has boosted the performance and usability of the new pathway
      diagram viewer, providing a robust, scalable and easy-to-integrate solution to
      pathway visualization. As graph-based visualization of complex data is a frequent
      challenge in bioinformatics, many of the individual strategies presented here are
      applicable to a wide range of web-based bioinformatics resources. Availability
      and implementation: Reactome is available online at: https://reactome.org. The
      diagram viewer is part of the Reactome pathway browser
      (https://reactome.org/PathwayBrowser/) and also available as a stand-alone widget
      at: https://reactome.org/dev/diagram/. The source code is freely available at:
      https://github.com/reactome-pwp/diagram. Contact: fabregat@ebi.ac.uk or
      hhe@ebi.ac.uk. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29186352
TI  - ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular
      Viability and Clonogenic Growth After DNA Damage.
AB  - Prolactin (PRL) acts as a survival factor for breast cancer cells, but the PRL
      signaling pathway and the mechanism are unknown. Previously, we identified the
      master chaperone, heat shock protein 90 (HSP90) alpha, as a prolactin-Janus
      kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) target
      gene involved in survival, and here we investigated the role of HSP90 in the
      mechanism of PRL-induced viability in response to DNA damage. The ataxia
      telangiectasia mutated kinase (ATM) protein plays a critical role in the cellular
      response to double-strand DNA damage. We observed that PRL increased viability of
      breast cancer cells treated with doxorubicin or etoposide. The increase in
      cellular resistance is specific to the PRL receptor, because the PRL receptor
      antagonist, Delta1-9-G129R-hPRL, prevented the increase in viability. Two
      different HSP90 inhibitors, 17-allylamino-17-demethoxygeldanamycin and BIIB021,
      reduced the PRL-mediated increase in cell viability of doxorubicin-treated cells
      and led to a decrease in JAK2, ATM, and phosphorylated ATM protein levels.
      Inhibitors of JAK2 (G6) and ATM (KU55933) abolished the PRL-mediated increase in
      cell viability of DNA-damaged cells, supporting the involvement of each, as well
      as the crosstalk of ATM with the PRL pathway in the context of DNA damage. Drug
      synergism was detected between the ATM inhibitor (KU55933) and doxorubicin and
      between the HSP90 inhibitor (BIIB021) and doxorubicin. Short interfering RNA
      directed against ATM prevented the PRL-mediated increase in cell survival in two
      dimensional cell culture, three-dimensional collagen gel cultures, and clonogenic
      cell survival, after doxorubicin treatment. Our results indicate that ATM
      contributes to the PRL-JAK2-STAT5-HSP90 pathway in mediating cellular resistance
      to DNA-damaging agents.

PMID- 29186354
TI  - Frequency of Maternal Touch Predicts Resting Activity and Connectivity of the
      Developing Social Brain.

PMID- 29186353
TI  - Prevalence and clinical association of gene mutations through multiplex mutation
      testing in patients with NSCLC: results from the ETOP Lungscape Project.
AB  - Background: Reported prevalence of driver gene mutations in non-small-cell lung
      cancer (NSCLC) is highly variable and clinical correlations are emerging. Using
      NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform
      Lungscape iBiobank, we explore the epidemiology of mutations and association to
      clinicopathologic features and patient outcome (relapse-free survival, time-to
      relapse, overall survival). Methods: Clinically annotated, resected stage I-III
      NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based
      multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of
      the ~150 (13 genes) mutations covered in the multiplex test. Results: Multiplex
      testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median
      follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently
      extracted DNA quality and quantity was generally good. Average DNA yield/case was
      2.63 ug; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of
      included cases allowed the complete panel of mutations to be tested. Most common
      were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%,
      5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more
      frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation
      prevalence did not differ between histology groups. EGFR mutations were found
      predominantly in never smokers; KRAS in current/former smokers. For all the above
      mutations, there was no difference in outcome between mutated and non-mutated
      cases. Conclusion: Archival FFPE NSCLC material is adequate for multiplex
      mutation analysis. In this large, predominantly European, clinically annotated
      stage I-III NSCLC cohort, none of the mutations characterized showed prognostic
      significance.

PMID- 29186355
TI  - Global proteomics profiling improves drug sensitivity prediction: results from a
      multi-omics, pan-cancer modeling approach.
AB  - Motivation: Proteomics profiling is increasingly being used for molecular
      stratification of cancer patients and cell-line panels. However, systematic
      assessment of the predictive power of large-scale proteomic technologies across
      various drug classes and cancer types is currently lacking. To that end, we
      carried out the first pan-cancer, multi-omics comparative analysis of the
      relative performance of two proteomic technologies, targeted reverse phase
      protein array (RPPA) and global mass spectrometry (MS), in terms of their
      accuracy for predicting the sensitivity of cancer cells to both cytotoxic
      chemotherapeutics and molecularly targeted anticancer compounds. Results: Our
      results in two cell-line panels demonstrate how MS profiling improves drug
      response predictions beyond that of the RPPA or the other omics profiles when
      used alone. However, frequent missing MS data values complicate its use in
      predictive modeling and required additional filtering, such as focusing on
      completely measured or known oncoproteins, to obtain maximal predictive
      performance. Rather strikingly, the two proteomics profiles provided
      complementary predictive signal both for the cytotoxic and targeted compounds.
      Further, information about the cellular-abundance of primary target proteins was
      found critical for predicting the response of targeted compounds, although the
      non-target features also contributed significantly to the predictive power. The
      clinical relevance of the selected protein markers was confirmed in cancer
      patient data. These results provide novel insights into the relative performance
      and optimal use of the widely applied proteomic technologies, MS and RPPA, which
      should prove useful in translational applications, such as defining the best
      combination of omics technologies and marker panels for understanding and
      predicting drug sensitivities in cancer patients. Availability and
      implementation: Processed datasets, R as well as Matlab implementations of the
      methods are available at https://github.com/mehr-een/bemkl-rbps. Contact:
      mehreen.ali@helsinki.fi or tero.aittokallio@fimm.fi. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29186356
TI  - Altered caudate connectivity is associated with executive dysfunction after
      traumatic brain injury.
AB  - Traumatic brain injury often produces executive dysfunction. This characteristic
      cognitive impairment often causes long-term problems with behaviour and
      personality. Frontal lobe injuries are associated with executive dysfunction, but
      it is unclear how these injuries relate to corticostriatal interactions that are
      known to play an important role in behavioural control. We hypothesized that
      executive dysfunction after traumatic brain injury would be associated with
      abnormal corticostriatal interactions, a question that has not previously been
      investigated. We used structural and functional MRI measures of connectivity to
      investigate this. Corticostriatal functional connectivity in healthy individuals
      was initially defined using a data-driven approach. A constrained independent
      component analysis approach was applied in 100 healthy adult dataset from the
      Human Connectome Project. Diffusion tractography was also performed to generate
      white matter tracts. The output of this analysis was used to compare
      corticostriatal functional connectivity and structural integrity between groups
      of 42 patients with traumatic brain injury and 21 age-matched controls.
      Subdivisions of the caudate and putamen had distinct patterns of functional
      connectivity. Traumatic brain injury patients showed disruption to functional
      connectivity between the caudate and a distributed set of cortical regions,
      including the anterior cingulate cortex. Cognitive impairments in the patients
      were mainly seen in processing speed and executive function, as well as increased
      levels of apathy and fatigue. Abnormalities of caudate functional connectivity
      correlated with these cognitive impairments, with reductions in right caudate
      connectivity associated with increased executive dysfunction, information
      processing speed and memory impairment. Structural connectivity, measured using
      diffusion tensor imaging between the caudate and anterior cingulate cortex was
      impaired and this also correlated with measures of executive dysfunction. We show
      for the first time that altered subcortical connectivity is associated with large
      scale network disruption in traumatic brain injury and that this disruption is
      related to the cognitive impairments seen in these patients.

PMID- 29186357
TI  - Outcome of ankle arthrodesis and ankle prosthesis: a review of the current
      status.
AB  - Introduction: In advanced stages of ankle osteoarthritis (OA), ankle arthrodesis
      (AA) or total ankle arthroplasty (TAR) may be necessary. Our purpose is to
      compare AA and total ankle replacement for the surgical management of end stage
      ankle OA. Sources of data: We conducted a literature search of PubMed, Medline,
      CINAHL, Cochrane, Embase and Google Scholar databases using the terms 'ankle' in
      combination with 'OA', 'arthrodesis', 'arthroplasty', 'joint fusion', 'joint
      replacement'. Studies where treatment was exclusively total ankle replacement or
      AA were excluded. Treatment characteristics and outcome parameters (overall
      postoperative outcome and complication rate) were reviewed. Areas of agreement:
      When counseling patients who are considering their options with regard to ankle
      arthritis treatment, surgeons should determine on an individual basis which
      procedure is more suitable. Areas of controversy: TAR has become an accepted
      treatment for end-stage OA, but revision rates for TAR are significant higher
      than for AA (odds ratio 2.28 95% confidence interval [CI], 1.63-3.19; P <
      0.0001). Growing points: The results of TAA are gradually improving, but the
      procedure cannot yet be recommended for the routine management of ankle OA. Areas
      timely for developing research: Although there is some evidence to support TAR to
      conserve ankle motion and offer improved function and decreased pain with high
      satisfaction rates, revision rates for TAR are significantly higher than revision
      rates for AA. Proper patient selection should be better addressed in future
      studies for successful treatment of end-stage ankle OA. Level of evidence:
      Systematic review, level III.

PMID- 29186358
TI  - Dipteran Diversity and Ecological Succession on Dead Pigs in Contrasting Mountain
      Habitats of Chiapas, Mexico.
AB  - A comparative study of Diptera communities associated with pig carcasses was
      carried out in urban and natural settings in tropical mountain habitats of
      Southern Mexico. Schoenly-type traps were used to set out pig carcasses during 68
      d of sampling effort. In total, 1,703 adult Diptera specimens were collected in
      both localities combined, and recording a total of 30 (morpho) species and 19
      families. Compared to natural habitats, a significantly greater diversity in
      urban habitats, as well as a faster decomposition process of carcasses, was
      detected. Significant differences were also detected for the composition and
      structure of Dipteran communities between urban and natural sites. Dominant
      species of Calliphoridae for natural and urban habitats were represented by
      Compsomyiops spp. and Cochliomyia macellaria (Fabricius; Diptera: Calliphoridae),
      respectively. The properties of indicator species for urban and natural sites are
      discussed. Twenty Dipteran species were significantly associated to different
      decomposition stages. Such affinity would allow for estimating the post-mortem
      interval (PMI) in comparable situations.

PMID- 29186359
TI  - In the Piriform Cortex, the Primary Impetus for Information Encoding through
      Synaptic Plasticity Is Provided by Descending Rather than Ascending Olfactory
      Inputs.
AB  - Information encoding by means of persistent changes in synaptic strength supports
      long-term information storage and memory in structures such as the hippocampus.
      In the piriform cortex (PC), that engages in the processing of associative
      memory, only short-term synaptic plasticity has been described to date, both in
      vitro and in anesthetized rodents in vivo. Whether the PC maintains changes in
      synaptic strength for longer periods of time is unknown: Such a property would
      indicate that it can serve as a repository for long-term memories. Here, we
      report that in freely behaving animals, frequency-dependent synaptic plasticity
      does not occur in the anterior PC (aPC) following patterned stimulation of the
      olfactory bulb (OB). Naris closure changed action potential properties of aPC
      neurons and enabled expression of long-term potentiation (LTP) by OB stimulation,
      indicating that an intrinsic ability to express synaptic plasticity is present.
      Odor discrimination and categorization in the aPC is supported by descending
      inputs from the orbitofrontal cortex (OFC). Here, OFC stimulation resulted in LTP
      (>4 h), suggesting that this structure plays an important role in promoting
      information encoding through synaptic plasticity in the aPC. These persistent
      changes in synaptic strength are likely to comprise a means through which long
      term memories are encoded and/or retained in the PC.

PMID- 29186360
TI  - Longitudinal Functional Brain Mapping in Supernormals.
AB  - Prevention of age-related cognitive decline is an increasingly important topic.
      Recently, increased attention is being directed at understanding biological
      models of successful cognitive aging. Here, we examined resting-state brain
      regional low-frequency oscillations using functional magnetic resonance imaging
      in 19 older adults with excellent cognitive abilities (Supernormals), 28 older
      adults with normative cognition, 57 older adults with amnestic mild cognitive
      impairment, and 26 with Alzheimer's disease. We identified a "Supernormal map", a
      set of regions whose oscillations were resistant to the aging-associated
      neurodegenerative process, including the right fusiform gyrus, right middle
      frontal gyrus, right anterior cingulate cortex, left middle temporal gyrus, left
      precentral gyrus, and left orbitofrontal cortex. The map was unique to the
      Supernormals, differentiated this group from cognitive average-ager comparisons,
      and predicted a 1-year change in global cognition (indexed by the Montreal
      Cognitive Assessment scores, adjusted R2 = 0.68). The map was also correlated to
      Alzheimer's pathophysiological features (beta-amyloid/pTau ratio, adjusted R2 =
      0.66) in participants with and without cognitive impairment. These findings in
      phenotypically successful cognitive agers suggest a divergent pattern of brain
      regions that may either reflect inherent neural integrity that contributes to
      Supernormals' cognitive success, or alternatively indicate adaptive
      reorganization to the demands of aging.

PMID- 29186362
TI  - shinyCircos: an R/Shiny application for interactive creation of Circos plot.
AB  - Summary: Creation of Circos plot is one of the most efficient approaches to
      visualize genomic data. However, the installation and use of existing tools to
      make Circos plot are challenging for users lacking of coding experiences. To
      address this issue, we developed an R/Shiny application shinyCircos, a graphical
      user interface for interactive creation of Circos plot. shinyCircos can be easily
      installed either on computers for personal use or on local or public servers to
      provide online use to the community. Furthermore, various types of Circos plots
      could be easily generated and decorated with simple mouse-click. Availability and
      implementation: shinyCircos and its manual are freely available at
      https://github.com/venyao/shinyCircos. shinyCircos is deployed at
      https://yimingyu.shinyapps.io/shinycircos/ and http://shinycircos.ncpgr.cn/ for
      online use. Contact: diana1983941@mail.hzau.edu.cn or yaowen@henau.edu.cn.

PMID- 29186361
TI  - PKK deletion in basal keratinocytes promotes tumorigenesis after chemical
      carcinogenesis.
AB  - Squamous cell carcinoma (SCC) of the skin is a keratinocyte malignancy
      characterized by tumors presenting on sun-exposed areas with surgery being the
      mainstay treatment. Despite advances in targeted therapy in other skin cancers,
      such as basal cell carcinoma and melanoma, there have been no such advances in
      the treatment of SCC. This is partly due to an incomplete knowledge of the
      pathogenesis of SCC. We have recently identified a protein kinase C-associated
      kinase (PKK) as a potential tumor suppressor in SCC. We now describe a novel
      conditional PKK knockout mouse model, which demonstrates that PKK deficiency
      promotes SCC formation during chemically induced tumorigenesis. Our results
      further support that PKK functions as a tumor suppressor in skin keratinocytes
      and is important in the pathogenesis of SCC of the skin. We further define the
      interactions of keratinocyte PKK with TP63 and NF-kappaB signaling, highlighting
      the importance of this protein as a tumor suppressor in SCC development.

PMID- 29186363
TI  - Transformation of Visual Representations Across Ventral Stream Body-selective
      Patches.
AB  - Although the neural processing of visual images of bodies is critical for
      survival, it is much less well understood than face processing. Functional
      imaging studies demonstrated body selective regions in primate inferior temporal
      cortex. To advance our understanding of how the visual brain represents bodies,
      we compared the representation of animate and inanimate objects in two such body
      patches with fMRI-guided single unit recordings in rhesus monkeys. We found that
      the middle Superior Temporal Sulcus body patch (MSB) distinguishes to a greater
      extent bodies from non-bodies than the anterior Superior Temporal Sulcus body
      patch (ASB). Importantly, ASB carried more viewpoint-tolerant information about
      body posture and body identity than MSB, while MSB showed greater orientation
      selectivity. Combined with previous work on faces, this suggests that an increase
      in view-tolerant representations, coupled with a refined individuation, along the
      visual hierarchy is a general property of information processing within the
      inferior temporal cortex.

PMID- 29186364
TI  - Efficacy and Safety of Oseltamivir in Children: Systematic Review and Individual
      Patient Data Meta-analysis of Randomized Controlled Trials.
AB  - Background: Oseltamivir has been used to treat children with influenza for nearly
      2 decades, with treatment currently approved for infants aged >=2 weeks. However,
      efficacy and safety remain controversial. Newer randomized, placebo-controlled
      trials (RCTs), not included in previous meta-analyses, can add to the evidence
      base. Methods: We conducted a systematic review to identify RCTs of oseltamivir
      therapy in children. We obtained individual patient data and examined protocol
      defined outcomes. We then conducted a 2-stage, random-effects meta-analysis to
      determine the efficacy of treatment in reducing the duration of illness,
      estimated using differences in restricted mean survival time (RMST) by treatment
      group. We also examined complications and safety. Results: We identified 5 trials
      that included 2561 patients in the intention-to-treat (ITT) and 1598 in the
      intention-to-treat infected (ITTI) populations. Overall, oseltamivir treatment
      significantly reduced the duration of illness in the ITTI population (RMST
      difference, -17.6 hours; 95% confidence interval [CI], -34.7 to -0.62 hours). In
      trials that enrolled patients without asthma, the difference was larger (-29.9
      hours; 95% CI, -53.9 to -5.8 hours). Risk of otitis media was 34% lower in the
      ITTI population. Vomiting was the only adverse event with a significantly higher
      risk in the treatment group. Conclusions: Despite substantial heterogeneity in
      pediatric trials, we found that treatment with oseltamivir significantly reduced
      the duration of illness in those with influenza and lowered the risk of
      developing otitis media. Alternative endpoints may be required to evaluate the
      efficacy of oseltamivir in pediatric patients with asthma.

PMID- 29186366
TI  - Human endometrial stromal cell decidualization requires transcriptional
      reprogramming by PLZF.
AB  - Infertility and early embryo miscarriage is linked to inadequate endometrial
      decidualization. Although transcriptional reprogramming is known to drive
      decidualization in response to progesterone, the key signaling effectors that
      directly mediate this hormone response are not fully known. This knowledge gap is
      clinically significant because identifying the early signals that directly
      mediate progesterone-driven decidualization will address some of the current
      limitations in diagnosing and therapeutically treating patients at most risk for
      early pregnancy loss. We recently revealed that the promyelocytic leukemia zinc
      finger (PLZF) is a direct target of the progesterone receptor and is essential
      for decidualization of human endometrial stromal cells (hESCs). The purpose of
      this current work was to identify the genome-wide transcriptional program that is
      controlled by PLZF during hESC decidualization using an established in vitro hESC
      culture model, siRNA-mediated knockdown methods, and RNA-sequencing technology
      followed by bioinformatic analysis and validation. We discovered that PLZF is
      critical in the regulation of genes that are involved in cellular processes that
      are essential for the archetypal morphological and functional changes that occur
      when hESCs transform into epithelioid decidual cells such as proliferation and
      cell motility. We predict that the transcriptome datasets identified in this
      study will not only contribute to a broader understanding of PLZF-dependent
      endometrial decidualization at the molecular level but may advance the
      development of more effective molecular diagnostics and therapeutics for the
      clinical management of female infertility and subfertility that is based on a
      dysfunctional endometrium.

PMID- 29186367
TI  - Vascular peroxidase 1 mediates hypoxia-induced pulmonary artery smooth muscle
      cell proliferation, apoptosis resistance and migration.
AB  - Aims: Reactive oxygen species (ROS) play essential roles in the pulmonary
      vascular remodelling associated with hypoxia-induced pulmonary hypertension (PH).
      Vascular peroxidase 1 (VPO1) is a newly identified haeme-containing peroxidase
      that accelerates oxidative stress development in the vasculature. This study
      aimed to determine the potential role of VPO1 in hypoxia-induced PH-related
      vascular remodelling. Methods and results: The vascular morphology and VPO1
      expression were assessed in the pulmonary arteries of Sprague-Dawley (SD) rats.
      Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and VPO1
      expression and HOCl production were significantly increased in hypoxic rats,
      which also exhibited obvious vascular remodelling. Furthermore, a hypoxia-induced
      PH model was generated by exposing primary rat pulmonary artery smooth muscle
      cells (PASMCs) to hypoxic conditions (3% O2, 48 h), which significantly increased
      the expression of NOX4 and VPO1 and the production of HOCl. These hypoxic changes
      were accompanied by enhanced proliferation, apoptosis resistance, and migration.
      In PASMCs, hypoxia-induced changes, including effects on the expression of cell
      cycle regulators (cyclin B1 and cyclin D1), apoptosis-related proteins (bax, bcl
      2, and cleaved caspase-3), migration promoters (matrix metalloproteinases 2 and
      9), and NF-kappaB expression, as well as the production of HOCl, were all
      inhibited by silencing VPO1 with small interfering RNAs. Moreover, treatment with
      HOCl under hypoxic conditions upregulated NF-kappaB expression and enhanced
      proliferation, apoptosis resistance, and migration in PASMCs, whereas BAY 11-7082
      (an inhibitor of NF-kappaB) significantly inhibited these effects. Conclusion:
      Collectively, these results demonstrate that VPO1 promotes hypoxia-induced
      proliferation, apoptosis resistance, and migration in PASMCs via the
      NOX4/VPO1/HOCl/NF-kappaB signalling pathway.

PMID- 29186368
TI  - Corrigendum to: 'Contemporary results of aortic valve repair for congenital
      disease: lessons for management and staged strategy' [Eur J Cardiothorac Surg
      2017;52(3):581-587].

PMID- 29186369
TI  - Complicated infective endocarditis on mitral annular calcification with left
      ventricular pseudoaneurysm.

PMID- 29186371
TI  - A recurrent de novo mutation in TMEM106B causes hypomyelinating leukodystrophy.
AB  - Hypomyelinating leukodystrophies are a heterogeneous group of disorders with a
      clinical presentation that often includes early-onset nystagmus, ataxia and
      spasticity and a wide range of severity. Using next-generation sequencing
      techniques and GeneMatcher, we identified four unrelated patients with brain
      hypomyelination, all with the same recurrent dominant mutation, c.754G>A
      p.(Asp252Asn), in TMEM106B. The mutation was confirmed as de novo in three of the
      cases, and the mildly affected father of the fourth affected individual was
      confirmed as mosaic for this variant. The protein encoded by TMEM106B is poorly
      characterized but is reported to have a role in regulation of lysosomal
      trafficking. Polymorphisms in TMEM106B are thought to modify disease onset in
      frontotemporal dementia, but its relation to myelination is not understood.
      Clinical presentation in three of the four patients is remarkably benign compared
      to other hypomyelinating disorders, with congenital nystagmus and mild motor
      delay. These findings add TMEM106B to the growing list of genes causing
      hypomyelinating disorders and emphasize the essential role lysosomes play in
      myelination.

PMID- 29186365
TI  - High Treatment Uptake in Human Immunodeficiency Virus/Hepatitis C Virus
      Coinfected Patients After Unrestricted Access to Direct-Acting Antivirals in the
      Netherlands.
AB  - Background: The Netherlands has provided unrestricted access to direct-acting
      antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C
      virus (HCV) treatment uptake among patients coinfected with human
      immunodeficiency virus (HIV) and HCV. Methods: Data were obtained from the ATHENA
      HIV observational cohort in which >98% of HIV-infected patients ever registered
      since 1998 are included. Patients were included if they ever had 1 positive HCV
      RNA result, did not have spontaneous clearance, and were known to still be in
      care. Treatment uptake and outcome were assessed. When patients were treated more
      than once, data were included from only the most recent treatment episode. Data
      were updated until February 2017. In addition, each treatment center was queried
      in April 2017 for a data update on DAA treatment and achieved sustained
      virological response. Results: Of 23574 HIV-infected patients ever linked to
      care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons
      who [formerly] injected drugs, and 15% with another HIV transmission route)
      fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated
      HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection
      cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have
      sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment
      results were pending in 6% (66 of 1022). Overall, 187 patients had never
      initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa-based
      regimen had failed in 54. Conclusions: Fifteen months after unrestricted DAA
      availability the majority of HIV/HCV-coinfected patients in the Netherlands have
      their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This
      rapid treatment scale-up may contribute to future HCV elimination among these
      patients.

PMID- 29186372
TI  - Irritable Bowel-like Symptoms in Ulcerative Colitis are as Common in Patients in
      Deep Remission as in Inflammation: Results From a Population-based Study [the
      IBSEN Study].
AB  - Background and Aims: An increased prevalence of irritable bowel syndrome [IBS]
      like symptoms has been reported in patients with ulcerative colitis [UC]. Whether
      ongoing inflammation increases the prevalence of such symptoms is unknown. The
      aims of this study were to determine the prevalence of IBS-like symptoms in a
      population-based cohort of UC patients 20 years after diagnosis, and to assess
      the possible association between such symptoms and ongoing inflammation. Methods:
      Patients diagnosed with UC between 1990 and 1994, in a geographically well
      defined area, were included in a prospective follow-up study, and IBS symptoms
      according to Rome III criteria were recorded 20 years after diagnosis. The
      patients underwent colonoscopy with biopsies and/or the level of faecal
      calprotectin was analysed. Results: A total of 260 patients answered the Rome III
      questionnaire. The overall prevalence of IBS-like symptoms was 27%. In patients
      who had no signs of inflammation in colonic biopsies [n = 96] [deep remission],
      the prevalence was 29%. No difference in prevalence of IBS-like symptoms was
      found between patients with ongoing inflammation and patients in deep remission.
      Conclusions: IBS-like symptoms in UC patients are frequent after 20 years of
      disease. Deep remission did not change the frequency of IBS-like symptoms.

PMID- 29186370
TI  - Comparative Genomics of Pathogenic and Nonpathogenic Beetle-Vectored Fungi in the
      Genus Geosmithia.
AB  - Geosmithia morbida is an emerging fungal pathogen which serves as a model for
      examining the evolutionary processes behind pathogenicity because it is one of
      two known pathogens within a genus of mostly saprophytic, beetle-associated,
      fungi. This pathogen causes thousand cankers disease in black walnut trees and is
      vectored into the host via the walnut twig beetle. Geosmithia morbida was first
      detected in western United States and currently threatens the timber industry
      concentrated in eastern United States. We sequenced the genomes of G. morbida in
      a previous study and two nonpathogenic Geosmithia species in this work and
      compared these species to other fungal pathogens and nonpathogens to identify
      genes under positive selection in G. morbida that may be associated with
      pathogenicity. Geosmithia morbida possesses one of the smallest genomes among the
      fungal species observed in this study, and one of the smallest fungal pathogen
      genomes to date. The enzymatic profile in this pathogen is very similar to its
      nonpathogenic relatives. Our findings indicate that genome reduction or retention
      of a smaller genome may be an important adaptative force during the evolution of
      a specialized lifestyle in fungal species that occupy a specificniche, such as
      beetle vectored tree pathogens. We also present potential genes under selection
      in G. morbida that could be important for adaptation to a pathogenic lifestyle.

PMID- 29186374
TI  - Interview with Professor Valter Longo.

PMID- 29186373
TI  - CCR2 expression on circulating monocytes is associated with arterial wall
      inflammation assessed by 18F-FDG PET/CT in patients at risk for cardiovascular
      disease.
AB  - Aims: Circulating monocytes infiltrate the plaque and differentiate into
      macrophages, contributing to an inflammatory environment which is associated with
      higher risk of cardiovascular events. Although the pivotal role of circulating
      monocytes in plaque inflammation has been firmly established, the search
      continues to identify specific monocyte subsets that may be especially
      atherogenic. Therefore, we evaluated the relation between monocyte phenotype,
      particularly surface receptor expression, and arterial wall inflammation in
      patients at increased cardiovascular risk. Methods and results: We performed a
      multivariate linear regression analysis in 79 patients at increased
      cardiovascular risk who had both an 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography to assess arterial wall inflammation and extensive
      monocyte characterization (using flow cytometry). We found that CCR2, a monocyte
      chemokine receptor essential for transmigration, significantly correlates with
      arterial wall inflammation. This relationship was independent of traditional
      cardiovascular risk factors and statin use (beta = 0.429, P = 0.015). We found no
      relation between arterial wall inflammation and monocyte count or monocyte
      subsets, namely CD14+CD16-, CD14+CD16+, CD14+CD16 ++, CCR5+, CD18+, CD11b+, or
      CD11c+ monocytes. Conclusion: Monocyte CCR2 expression is associated with
      arterial wall inflammation in patients at increased cardiovascular risk. Our data
      warrant further studies to assess if inhibition of CCR2 may attenuate
      atherosclerotic plaque inflammation.

PMID- 29186375
TI  - Unilateral pulmonary oedema after minimally invasive mitral valve surgery: a
      single-centre experience.
AB  - OBJECTIVES: Unilateral pulmonary oedema (UPE) is a rare but potentially life
      threatening complication that has been described after minimally invasive mitral
      valve surgery (MICS). Over the last 8 years, we have witnessed, in our
      institution, several cases of severe UPE requiring immediate postoperative
      extracorporeal life support after MICS. Reviewing the available literature, data
      regarding this complication after MICS are rare. Consequently, we decided to
      retrospectively analyse patients scheduled for MICS in our institution. METHODS:
      After approval by our institutional review board, 256 MICS patients were
      analysed. As a primary end-point, we defined a newly developed UPE,
      radiographically evident within the first 24 h postoperatively. Secondary end
      points were length of stay in the intensive care unit, length of stay in the
      hospital and in-hospital mortality. Chest radiographs were analysed by an
      independent consultant of radiology. RESULTS: Fifty-one (19.9%) patients showed
      increased right-sided pulmonary vascular congestion in the 1st postoperative
      chest radiography performed in the intensive care unit. Five (1.95%) patients
      immediately required extracorporeal life support after admission to the intensive
      care unit. Cardiopulmonary bypass time was significantly longer in the UPE group
      [UPE vs non-UPE 213 (49) vs 196 (43) min; P = 0.013]. More patients with UPE
      showed a preoperative increase of C-reactive protein >0.4265 mg/dl (P = 0.05).
      Logistic regression analysis identified a preoperative increase in C-reactive
      protein >0.4265 mg/dl as well as a prolonged cardiopulmonary bypass time (odds
      ratio 1.009, 95% confidence level 1.002-1.016; P = 0.014) independent risk
      factors, significantly associated with the development of UPE (odds ratio 2.583,
      95% confidence interval 1.275-5.233; P = 0.008), a prolonged cardiopulmonary
      bypass time (odds ratio 1.009, 95% confidence interval 1.002-1.016; P = 0.014).
      The presence of pulmonary hypertension (odds ratio 0.273, 95% confidence interval
      0.08-0.84; P = 0.02) seemed to be a protective factor regarding the genesis of
      UPE. CONCLUSIONS: In accordance with the rarely available literature regarding
      UPE after MICS, our analysis led us to hypothesize the possibility of an
      inflammatory disposition for UPE. The role of pulmonary hypertension remains
      unclear in our patient population. Clinical Trials Number: NCT02655094.

PMID- 29186376
TI  - Evaluation of Semiochemical-Baited Traps for Monitoring the Pea Leaf Weevil,
      Sitona lineatus (Coleoptera: Curculionidae) in Field Pea Crops.
AB  - The pea leaf weevil (PLW), Sitona lineatus L., is a pest of field pea (Pisum
      sativum L.) and faba bean (Vicia faba L.) that recently invaded the Canadian
      Prairie Provinces. Although most damage is done by larvae that feed on root
      nodules, adults are easier to monitor than larvae. Both male and female weevils
      respond to a male-produced aggregation pheromone and to volatiles released by
      host plants. The current study tests the attractiveness of synthetic aggregation
      pheromone, 4-methyl-3,5-heptanedione, and host plant volatiles linalool, (Z)-3
      hexenol, and (Z)-3-hexenyl acetate to PLWs in spring when weevils are
      reproductively active and in fall when weevils seek overwintering sites.
      Different combinations of semiochemical lures at various doses, released from a
      variety of devices were tested in pitfall traps. Semiochemical-baited traps
      captured both male and female weevils in both seasons but the sex ratio varied
      with season. Weevils did not respond in a dose-dependent manner to pheromone, as
      all pheromone lures were equally attractive. Pheromone release rate was
      determined by the release device and not the pheromone dose in the lure. The
      addition of plant volatiles sometimes increased weevil captures but plant
      volatiles alone were not attractive to PLW adults. An additional study tested the
      effect of trap type on weevil capture. Of the 12 different trap types tested,
      pheromone-baited pitfall traps were most successful in attracting and retaining
      weevils. Bycatch of other Sitona species was limited to a few specimens of the
      sweet clover weevil, Sitona cylindricollis Fahraeus.

PMID- 29186378
TI  - PipelineDog: a simple and flexible graphic pipeline construction and maintenance
      tool.
AB  - Summary: Analysis pipelines are an essential part of bioinformatics research, and
      ad hoc pipelines are frequently created by researchers for prototyping and proof
      of-concept purposes. However, most existing pipeline management system or
      workflow engines are too complex for rapid prototyping or learning the pipeline
      concept. A lightweight, user-friendly and flexible solution is thus desirable. In
      this study, we developed a new pipeline construction and maintenance tool,
      PipelineDog. This is a web-based integrated development environment with a modern
      web graphical user interface. It offers cross-platform compatibility, project
      management capabilities, code formatting and error checking functions and an
      online repository. It uses an easy-to-read/write script system that encourages
      code reuse. With the online repository, it also encourages sharing of pipelines,
      which enhances analysis reproducibility and accountability. For most users,
      PipelineDog requires no software installation. Overall, this web application
      provides a way to rapidly create and easily manage pipelines. Availability and
      implementation: PipelineDog web app is freely available at
      http://web.pipeline.dog. The command line version is available at
      http://www.npmjs.com/package/pipelinedog and online repository at
      http://repo.pipeline.dog. Contact: ysun@kean.edu or xing@biology.rutgers.edu or
      ysun@diagnoa.com. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29186377
TI  - Oxytocin-Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice.
AB  - Social stress has deteriorating effects on various psychiatric diseases. In
      animal models, exposure to socially dominant conspecifics (i.e., social defeat
      stress) evokes a species-specific defeat posture via unknown mechanisms. Oxytocin
      neurons have been shown to be activated by stressful stimuli and to have
      prosocial and anxiolytic actions. The roles of oxytocin during social defeat
      stress remain unclear. Expression of c-Fos, a marker of neuronal activation, in
      oxytocin neurons and in oxytocin receptor-expressing neurons was investigated in
      mice. The projection of oxytocin neurons was examined with an anterograde viral
      tracer, which induces selective expression of membrane-targeted palmitoylated
      green fluorescent protein in oxytocin neurons. Defensive behaviors during double
      exposure to social defeat stress in oxytocin receptor-deficient mice were
      analyzed. After social defeat stress, expression of c-Fos protein was increased
      in oxytocin neurons of the bed nucleus of the stria terminalis, supraoptic
      nucleus, and paraventricular hypothalamic nucleus. Expression of c-Fos protein
      was also increased in oxytocin receptor-expressing neurons of brain regions,
      including the ventrolateral part of the ventromedial hypothalamus and
      ventrolateral periaqueductal gray. Projecting fibers from paraventricular
      hypothalamic oxytocin neurons were found in the ventrolateral part of the
      ventromedial hypothalamus and in the ventrolateral periaqueductal gray. Oxytocin
      receptor-deficient mice showed reduced defeat posture during the second social
      defeat stress. These findings suggest that social defeat stress activates
      oxytocin-oxytocin receptor systems, and the findings are consistent with the view
      that activation of the oxytocin receptor in brain regions, including the
      ventrolateral part of the ventromedial hypothalamus and the ventrolateral
      periaqueductal gray, facilitates social defeat posture.

PMID- 29186379
TI  - Development of a high-density linkage map and chromosome segment substitution
      lines for Japanese soybean cultivar Enrei.
AB  - Using progeny of a cross between Japanese soybean Enrei and Chinese soybean
      Peking, we developed a high-density linkage map and chromosomal segment
      substitution lines (CSSLs). The map consists of 2,177 markers with polymorphism
      information for 32 accessions and provides a detailed genetic framework for these
      markers. The marker order on the linkage map revealed close agreement with that
      on the chromosome-scale assembly, Wm82.a2.v1. The differences, especially on Chr.
      5 and Chr. 11, in the present map provides information to identify regions in the
      genome assembly where additional information is required to resolve marker order
      and assign remaining scaffolds. To cover the entire soybean genome, we used 999
      BC3F2 backcross plants and selected 103 CSSLs carrying chromosomal segments from
      Peking in the genetic background of Enrei. Using these low-genetic-complexity
      resources, we dissected variation in traits related to flowering, maturity and
      yield into approximately 50 reproducible quantitative trait loci (QTLs) and
      evaluated QTLs with small genetic effects as single genetic factors in a uniform
      genetic background. CSSLs developed in this study may be good starting material
      for removing the unfavourable characteristics of Peking during pre-breeding and
      for isolation of genes conferring disease and stress resistance that have not yet
      been characterized.

PMID- 29186380
TI  - Impact of T-cell-mediated immune response on xenogeneic heart valve
      transplantation: short-term success and mid-term failure.
AB  - OBJECTIVES: Allogeneic frozen cryopreserved heart valves (allografts or
      homografts) are commonly used in clinical practice. A major obstacle for their
      application is the limited availability in particular for paediatrics. Allogeneic
      large animal studies revealed that alternative ice-free cryopreservation (IFC)
      results in better matrix preservation and reduced immunogenicity. The objective
      of this study was to evaluate xenogeneic (porcine) compared with allogeneic
      (ovine) IFC heart valves in a large animal study. METHODS: IFC xenografts and
      allografts were transplanted in 12 juvenile merino sheep for 1-12 weeks.
      Immunohistochemistry, ex vivo computed tomography scans and transforming growth
      factor-beta release profiles were analysed to evaluate postimplantation
      immunopathology. In addition, near-infrared multiphoton imaging and Raman
      spectroscopy were employed to evaluate matrix integrity of the leaflets. RESULTS:
      Acellular leaflets were observed in both groups 1 week after implantation.
      Allogeneic leaflets remained acellular throughout the entire study. In contrast,
      xenogeneic valves were infiltrated with abundant T-cells and severely thickened
      over time. No collagen or elastin changes could be detected in either group using
      multiphoton imaging. Raman spectroscopy with principal component analysis
      focusing on matrix-specific peaks confirmed no significant differences for
      explanted allografts. However, xenografts demonstrated clear matrix changes,
      enabling detection of distinct inflammatory-driven changes but without variations
      in the level of transforming growth factor-beta. CONCLUSIONS: Despite short-term
      success, mid-term failure of xenogeneic IFC grafts due to a T-cell-mediated
      extracellular matrix-triggered immune response was shown.

PMID- 29186381
TI  - Successful use of donor lungs after repairing severely injured pulmonary vein of
      donor lungs.

PMID- 29186382
TI  - A modified technique for orthotopic heart transplantation to minimize warm
      ischaemic time.
AB  - Prolonged allograft ischaemic time in heart transplantation adversely impacts the
      performance of the donor heart in the immediate postoperative period and
      ultimately results in decreased post-transplant survival. Therefore, optimal
      surgical technique for heart transplantation should aim to minimize allograft
      ischaemic time. Here, we report a case of successful orthotopic heart
      transplantation using a modified technique to reduce allograft ischaemic time and
      warm ischaemic time.

PMID- 29186383
TI  - Effects of Low Temperature on Spider Mite Control by Intermittent Ultraviolet-B
      Irradiation for Practical Use in Greenhouse Strawberries.
AB  - The application of ultraviolet-B (UVB) radiation to control spider mites is
      challenging as a key technology for integrated pest management (IPM) in
      greenhouse strawberries in Japan. To address this, concurrent use of phytoseiid
      mites and reduced UVB irradiance is desirable to ensure control effects in areas
      shaded from UVB radiation and to minimize the sunscald in winter, respectively.
      We designed experiments reproducing the UVB dose on the lower leaf surfaces in
      strawberry and evaluated the effects of intermittent UVB irradiation at midnight
      for practical application in the greenhouse and low temperature on the survival
      of the spider mite Tetranychus urticae Koch (Acari: Tetranychidae) and damage to
      the phytoseiid mite Neoseiulus californicus (McGregor) (Acari: Phytoseiidae). The
      midnight intermittent UVB irradiation effectively suppressed egg hatching and
      development of larvae of T. urticae, and the control effect was reinforced at 20
      degrees C (no eggs hatched at 0.13 kJ m-2 d-1) rather than, at 25 degrees C
      (70.8% eggs hatched). In contrast, the hatchability of N. californicus eggs was
      unaffected by intermittent UVB irradiation at 0.27 kJ m-2 d-1 at 25 degrees C and
      20 degrees C. However, residual effects of UVB irradiation to N. californicus
      eggs on survival of hatched larvae were seen, so that reducing the UVB dose is
      also advantageous for this phytoseiid mite. N. californicus showed a
      photoreactivation capacity, whereas their UVB tolerance was improved by prey
      species, suggesting the possibility of the improvement of phytoseiid mites by
      diet. The reduction of UVB dose and concurrent use of phytoseiid mites increase
      reliability of the UVB method in IPM strategies in strawberry greenhouse.

PMID- 29186384
TI  - PlanNET: homology-based predicted interactome for multiple planarian
      transcriptomes.
AB  - Motivation: Planarians are emerging as a model organism to study regeneration in
      animals. However, the little available data of protein-protein interactions
      hinders the advances in understanding the mechanisms underlying its regenerating
      capabilities. Results: We have developed a protocol to predict protein-protein
      interactions using sequence homology data and a reference Human interactome. This
      methodology was applied on 11 Schmidtea mediterranea transcriptomic sequence
      datasets. Then, using Neo4j as our database manager, we developed PlanNET, a web
      application to explore the multiplicity of networks and the associated sequence
      annotations. By mapping RNA-seq expression experiments onto the predicted
      networks, and allowing a transcript-centric exploration of the planarian
      interactome, we provide researchers with a useful tool to analyse possible
      pathways and to design new experiments, as well as a reproducible methodology to
      predict, store, and explore protein interaction networks for non-model organisms.
      Availability and implementation: The web application PlanNET is available at
      https://compgen.bio.ub.edu/PlanNET. The source code used is available at
      https://compgen.bio.ub.edu/PlanNET/downloads. Contact: jabril@ub.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29186385
TI  - Identifying simultaneous rearrangements in cancer genomes.
AB  - Motivation: The traditional view of cancer evolution states that a cancer genome
      accumulates a sequential ordering of mutations over a long period of time.
      However, in recent years it has been suggested that a cancer genome may instead
      undergo a one-time catastrophic event, such as chromothripsis, where a large
      number of mutations instead occur simultaneously. A number of potential
      signatures of chromothripsis have been proposed. In this work we provide a
      rigorous formulation and analysis of the "ability to walk the derivative
      chromosome" signature originally proposed by Korbel and Campbell (2013). In
      particular, we show that this signature, as originally envisioned, may not always
      be present in a chromothripsis genome and we provide a precise quantification of
      under what circumstances it would be present. We also propose a variation on this
      signature, the H/T alternating fraction, which allows us to overcome some of the
      limitations of the original signature. Results: We apply our measure to both
      simulated data and a previously analyzed real cancer dataset and find that the
      H/T alternating fraction may provide useful signal for distinguishing genomes
      having acquired mutations simultaneously from those acquired in a sequential
      fashion. Availability: An implementation of the H/T alternating fraction is
      available at https://bitbucket.org/oesperlab/ht-altfrac. Contact:
      loesper@carleton.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29186386
TI  - Gene Expression Pattern in Response to Cholecalciferol Supplementation Highlights
      Cubilin as a Major Protein of 25(OH)D Uptake in Adipocytes and Male Mice White
      Adipose Tissue.
AB  - It is well established that the active form of vitamin D (i.e., 1,25
      dihydroxyvitamin D [1,25(OH)2D]) regulates the expression of genes involved in
      its own metabolism and transport in the kidney and possibly in the liver.
      However, little is known about the transcriptional impact of cholecalciferol
      supplementation on white adipose tissue (WAT) and adipocytes, which are a major
      site of vitamin D and 25-hydroxyvitamin D [25(OH)D] storage in the organism. To
      fill this gap, we investigated the impact of cholecalciferol supplementation in
      WAT via a panel of genes coding for enzymes and proteins involved in vitamin D
      metabolism and uptake. Mice supplemented with cholecalciferol (15,000 IU/kg of
      body weight per day) for 4 days showed decreased messenger RNA (mRNA) levels of
      proteins involved in cholecalciferol metabolism (Cyp24a1, Cyp27a1) and decreased
      cubilin mRNA levels in WAT. These data were partly confirmed in 3T3-L1 adipocytes
      incubated with 1,25(OH)2D. The downregulation of cubilin mRNA observed in WAT and
      in 3T3-L1 was confirmed at the protein level in WAT and at the mRNA level in
      human primary adipocytes. Vitamin D receptor (VDR) agonist (EB1089) and RNA
      interference approaches demonstrated that VDR was involved in this regulation.
      Furthermore, chemical inhibitor and RNA inference analysis demonstrated that
      cubilin was involved in 25(OH)D uptake by adipocytes. This study established an
      overall snapshot of the genes regulated by cholecalciferol in mouse WAT and cell
      autonomously in adipocytes. We highlighted that the regulation of cubilin
      expression was mediated by a VDR-dependent mechanism, and we demonstrated that
      cubilin was involved in 25(OH)D uptake by adipocytes.

PMID- 29186387
TI  - Resveratrol Intake During Pregnancy and Lactation Modulates the Early Metabolic
      Effects of Maternal Nutrition Differently in Male and Female Offspring.
AB  - Poor maternal nutrition can have detrimental long-term consequences on energy
      homeostasis in the offspring. Resveratrol exerts antioxidant and antiobesity
      actions, but its impact during development remains largely unknown. We
      hypothesized that resveratrol intake during pregnancy and lactation could improve
      the effects of poor maternal nutrition on offspring metabolism. Wistar rats
      received a low-fat diet (LFD; 10.2% kcal from fat) or high-fat diet (HFD; 61.6%
      kcal from fat), with half of each group receiving resveratrol in their drinking
      water (50 mg/L) during pregnancy and lactation. Body weight (BW) of dams was
      measured at treatment onset and weaning [postnatal day (PND) 21] and of pups at
      birth and PND21, at which time dams and pups were euthanized. Although HFD dams
      consumed more energy, their BW at the end of lactation was unaffected. Mean
      litter size was not modified by maternal diet or resveratrol. At birth, male
      offspring from HFD and resveratrol (HFD + R) dams weighed less than those from
      LFD and resveratrol (LFD + R) dams. On PND21, pups of both sexes from HFD dams
      weighed more, had more visceral adipose tissue (VAT) and subcutaneous adipose
      tissue (SCAT), and had higher serum leptin levels than those from LFD dams.
      Resveratrol reduced BW, leptin, VAT, and SCAT, with females being more affected,
      but increased glycemia. Neuropeptide levels were unaffected by resveratrol. In
      conclusion, resveratrol intake during pregnancy and lactation decreased BW and
      adipose tissue content in offspring of dams on an HFD but did not affect
      offspring from LFD-fed dams, suggesting that the potential protective effects of
      resveratrol during gestation/lactation are diet dependent.

PMID- 29186389
TI  - The effect of colchicine administration on postoperative pleural effusion
      following lung resection: a randomized blinded placebo-controlled feasibility
      pilot study.
AB  - OBJECTIVES: This substudy of the colchicine for prevention of perioperative
      atrial fibrillation (COP-AF) pilot trial seeks to assess the effect of colchicine
      administration on the volume of postoperative pleural drainage, duration of chest
      tube in situ and length of stay following lung resection. METHODS: Between April
      2014 and April 2015, 100 patients undergoing lung resection at 2 tertiary care
      centres participated in a pilot blinded randomized trial comparing perioperative
      twice daily 0.6 mg of colchicine orally (n = 49) or placebo (n = 51) twice daily
      for 10 days. The primary outcome was total pleural drainage volume, which was
      recorded in 8-h intervals for the first 2 postoperative days per standardized
      protocol. RESULTS: Only 1 patient did not complete the trial. The mean volume of
      pleural drainage at 40-h mark postoperation was significantly less in the
      colchicine group (550.9 ml) compared with the placebo group (741.3 ml, P =
      0.039). Compared with the placebo group, the colchicine group showed
      significantly less mean pleural drainage on postoperative Day 2 (583.8 vs 763.3
      ml, P = 0.039) and beyond. There were no differences in mean time to chest tube
      removal (6.8 days for the colchicine group vs 5.9 days for the placebo group, P =
      0.585) and mean hospital length of stay (7.4 vs 6.9 days, P = 0.641).
      CONCLUSIONS: Oral colchicine is potentially effective in diminishing the amount
      of pleural drainage following lung resection and can be considered in patients at
      high risk of large postoperative pleural effusion. A full-scale, prospective
      placebo-controlled randomized trial is needed to assess the clinical significance
      of perioperative colchicine administration following oncological lung resection.

PMID- 29186388
TI  - Walking, Gross Motor Development, and Brain Functional Connectivity in Infants
      and Toddlers.
AB  - Infant gross motor development is vital to adaptive function and predictive of
      both cognitive outcomes and neurodevelopmental disorders. However, little is
      known about neural systems underlying the emergence of walking and general gross
      motor abilities. Using resting state fcMRI, we identified functional brain
      networks associated with walking and gross motor scores in a mixed cross
      sectional and longitudinal cohort of infants at high and low risk for autism
      spectrum disorder, who represent a dimensionally distributed range of motor
      function. At age 12 months, functional connectivity of motor and default mode
      networks was correlated with walking, whereas dorsal attention and posterior
      cingulo-opercular networks were implicated at age 24 months. Analyses of general
      gross motor function also revealed involvement of motor and default mode networks
      at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal,
      and subcortical networks additionally implicated at 24 months. These findings
      suggest that changes in network-level brain-behavior relationships underlie the
      emergence and consolidation of walking and gross motor abilities in the toddler
      period. This initial description of network substrates of early gross motor
      development may inform hypotheses regarding neural systems contributing to
      typical and atypical motor outcomes, as well as neurodevelopmental disorders
      associated with motor dysfunction.

PMID- 29186391
TI  - Longitudinal Trends in the Prevalence of Detectable HIV Viremia: Population-Based
      Evidence From Rural KwaZulu-Natal, South Africa.
AB  - Background: The prevalence of detectable viremia has previously been used to
      infer the potential for ongoing human immunodeficiency virus (HIV) transmission.
      To date, no study has evaluated the longitudinal change in the prevalence of
      detectable viremia within the HIV-positive community (PDV+) and the entire
      population (PDVP) using data from a sub-Saharan African setting. Methods: In
      2011, 2013, and 2014, we obtained 6752 HIV-positive and 15415 HIV-negative test
      results from a population-based surveillance system in the KwaZulu-Natal province
      of South Africa. We quantified the PDV+ as the proportion of the 6752 HIV
      positive results with a viral load >1550 copies/mL and the PDVP as the proportion
      of the 6752 HIV-positive and 15415 HIV-negative results with a viral load >1550
      copies/mL. Results: Between 2011 and 2014, the PDV+ decreased by 16.5 percentage
      points (pp) for women (from 71.8% to 55.3%) and 10.6 pp for men (from 77.8% to
      67.2%). However, a steady rise in the overall HIV prevalence, from 26.7% to
      32.4%, offset the declines in the PDV+ for both sexes. For women, the PDVP
      decreased by only 2.1 pp, from 21.3% to 19.2%, but for men, the PDVP actually
      increased by 1.6 pp, from 14.6% to 16.2%, over the survey period. Conclusions:
      The PDV+, which is currently being tracked under the UNAIDS 90-90-90 targets, may
      not be an accurate indicator of the potential for ongoing HIV transmission. There
      is a critical need for countries to monitor and report the prevalence of
      detectable viremia among all adults, irrespective of HIV status.

PMID- 29186392
TI  - Hawthorne effect reporting in orthodontic randomized controlled trials: truth or
      myth? Blessing or curse?
AB  - Objective: To investigate in 10 orthodontic journals how many randomized
      controlled trials (RCTs) considered the Hawthorne effect, and if considered, to
      determine whether it was related to the patients or the therapists involved in
      the trial and, finally, to discuss the Hawthorne effect in an educational way.
      Materials and methods: A search was performed on the Medline database, via
      PubMed, for publication type 'randomized controlled trial' published for each
      journal between 1 August 2007 and 31 July 2017. The American Journal of
      Orthodontics and Dentofacial Orthopedics, Angle Orthodontist, Australian
      Orthodontic Journal, Dental Press Journal of Orthodontics, European Journal of
      Orthodontics, Journal of Orthodontics, Journal of Orofacial Orthopedics, Korean
      Journal of Orthodontics, Orthodontics and Craniofacial Research and Progress in
      Orthodontics were assessed. Two independent reviewers extracted the data and
      identified whether the Hawthorne effect was considered or discussed in the
      articles and whether the Hawthorne effect was related to the behaviour of the
      patients, the therapists, or both. Results: The initial search generated 502
      possible trials. After applying the inclusion and exclusion criteria, 290 RCTs
      were included and assessed. The Hawthorne effect was considered or discussed in
      10 of 290 RCTs (3.4%), and all were related to the patients' and none to the
      therapists' behaviour. Conclusions: The Hawthorne effect reported in orthodontic
      RCTs was suboptimal. The researchers' lack of knowledge about this phenomenon is
      evident, despite evidence that the Hawthorne effect may cause over-optimistic
      results or false-positive bias.

PMID- 29186390
TI  - Direct Activation of Angiotensin II Type 2 Receptors Enhances Muscle
      Microvascular Perfusion, Oxygenation, and Insulin Delivery in Male Rats.
AB  - Angiotensin II receptors regulate muscle microvascular recruitment and the
      delivery of nutrients, oxygen, and insulin to muscle. Although angiotensin type 1
      receptor antagonism increases muscle microvascular perfusion and insulin action,
      angiotensin type 2 receptor blockade markedly restricts muscle microvascular
      blood volume and decreases muscle delivery of insulin. To examine the effects of
      direct type 2 receptor stimulation using Compound 21 (C21) on microvascular
      perfusion, insulin delivery and action, and tissue oxygenation in muscle,
      overnight-fasted adult male rats were infused with C21 systemically. C21 potently
      increased microvascular blood volume without altering microvascular flow velocity
      or blood pressure, resulting in a net increase in microvascular blood flow in
      muscle. This was associated with a substantial increase in muscle interstitial
      oxygen saturation and insulin delivery into the skeletal and cardiac muscle.
      These effects were neutralized by coinfusion of the type 2 receptor antagonist or
      nitric oxide synthase inhibitor. Superimposing C21 infusion on insulin infusion
      increased insulin-mediated whole body glucose disposal by 50%. C21 significantly
      relaxed the preconstricted distal saphenous artery ex vivo. We have concluded
      that direct type 2 receptor stimulation markedly increases muscle microvascular
      perfusion through nitric oxide biosynthesis and enhances insulin delivery and
      action in muscle. These findings provide a physiologic mechanistic insight into
      type 2 receptor modulation of insulin action and suggest that type 2 receptor
      agonists might have therapeutic potential in the management of diabetes and its
      associated complications.

PMID- 29186394
TI  - The association of invasive treatment with health status outcomes in patients
      with non-ST-elevation myocardial infarction and pre-infarct angina.

PMID- 29186395
TI  - Bacillus amyloliquefaciens ssp. plantarum F11 isolated from Algerian salty lake
      as a source of biosurfactants and bioactive lipopeptides.
AB  - In this study, we identified a new Bacillus strain isolated from an Algerian
      salty lake that produces metabolites that are active against Gram-positive and
      Gram-negative bacteria, as well as fungal pathogens. The draft genome sequence of
      the strain is presented herein. Genome sequence analysis identified the strain to
      be B. amyloliquefaciens subspecies plantarum F11, and showed that the strain
      carries the gene clusters for the production of a number of bioactive and surface
      active compounds. These include the lipopeptides surfactin and fengycin,
      antibacterial polyketides macrolactin and bacillaene, and a putative novel
      lanthipeptide, among others. Through an activity-guided purification method using
      hydrophobic interaction chromatographic techniques, we confirmed the ability of
      the strain to produce fengycin lipopeptides. The identities of the isolated
      fengycin homologs were ascertained through tandem mass spectrometry.

PMID- 29186393
TI  - Inappropriate doses of direct oral anticoagulants in real-world clinical
      practice: prevalence and associated factors. A subanalysis of the FANTASIIA
      Registry.
AB  - Aims: To describe the prevalence and associated factors of inappropriate doses of
      direct oral anticoagulants (DOAC) in a national registry of patients of real
      clinical practice. Methods and results : Five hundred and thirty outpatients with
      atrial fibrillation treated with DOAC were included in a prospective, national,
      multicentre study. The appropriateness of the doses of DOAC was defined according
      to the recommendations of the European Heart Rhythm Association. Mean age was 73
      +/- 9 years, with a 46% of women. Two hundred and sixty-seven patients were
      prescribed dabigatran, 190 rivaroxaban, and 73 apixaban. A total of 172 patients
      (32%) did not receive the appropriate dose: 93 patients received a lower dose
      (18%) and 79 patients a higher dose (15%). In the comparisons among the subgroups
      of inappropriately low, appropriate, and inappropriately high dose, we observed
      significant trends to older age (69 +/- 8 years vs. 73 +/- 10 years vs. 77 +/- 6
      years), more frequent female sex (37% vs. 46% vs. 59%), antiplatelet drugs (5%
      vs. 8% vs. 25%), rivaroxaban (14% vs. 38% vs. 53%), and apixaban use (5% vs. 15%
      vs. 19%), higher CHAD2DS2-VASc (3.00 +/- 1.38 vs. 3.58 +/- 1.67 vs. 4.59 +/-
      1.44) and HAS-BLED scores (1.83 +/- 0.87 vs. 1.92 +/- 1.07 vs. 2.47 +/- 1.13),
      lower body mass index (30 +/- 6 kg/m2 vs. 29 +/- 4 kg/m2 vs. 28 +/- 4 kg/m2) and
      glomerular filtration rate (74 +/- 27 mL/min vs. 70 +/- 22 mL/min vs. 63 +/- 16
      mL/min), and lower frequency of dabigatran use (81% vs. 47% vs. 28%) (all
      comparisons P <= 0.01). Conclusion: In this real-life study, 32% of patients
      received an inappropriate dose of DOAC. Several clinical factors can identify
      patients at risk of this situation.

PMID- 29186396
TI  - Genome sequencing of Chlamydia trachomatis serovars E and F reveals substantial
      genetic variation.
AB  - Chlamydia trachomatis (Ctr) is a bacterial pathogen that causes ocular,
      urogenital and lymph system infections in humans. It is highly abundant and among
      its serovars, E, F and D are most prevalent in sexually transmitted disease.
      However, the number of publicly available genome sequences of the serovars E and
      F, and thereby our knowledge about the molecular architecture of these serovars,
      is low. Here we sequenced the genomes of six E and F clinical isolates and one E
      lab strain, in order to study the genetic variance in these serovars. As observed
      before, the genomic variation inside the Ctr genomes is very low and the
      phylogenetic placement in comparison to publicly available genomes is as expected
      by ompA gene serotyping. However, we observed a large InDel carrying four to five
      open reading frames in one clinical E sample and in the E lab strain. We have
      also observed substantial variation on nucleotide and amino acid levels,
      especially in membrane proteins and secreted proteins. Furthermore, these two
      groups of proteins are also target for recombination events. One clinical F
      isolate was genetically heterogeneous and revealed the highest differences on
      nucleotide level in the pmpE gene.

PMID- 29186397
TI  - Images of atrial giant cell myocarditis.

PMID- 29186398
TI  - Oral anticoagulation: a step toward solving the puzzle of dementia related to
      atrial fibrillation?

PMID- 29186400
TI  - Metabolites associated with risk of developing mobility disability in the Health,
      Aging and Body Composition Study.
AB  - Background: Metabolic pathways that give rise to functional decline and mobility
      disability in older adults are incompletely understood. Methods: To identify
      metabolic perturbations that may impact functional decline, non-targeted
      metabolomics was used to measure 350 metabolites in baseline plasma from 313
      black men in the Health ABC Study (median age 74 years). Usual gait speed was
      measured over 20 meters. Cross-sectional relationships between gait speed and
      metabolites were explored with partial correlations adjusted for age, study site
      and smoking status. Risk of incident mobility disability (2 consecutive reports
      of severe difficulty walking 1/4 mile or climb 10 stairs) over 13 years of follow
      up was explored with cox regression models among 307 men who were initially free
      of mobility disability. Significance was determined at p<=0.01 and q (false
      discovery rate) <=0.30. Results: Two metabolites were correlated with gait speed;
      salicylurate (r=-0.19), and 2-hydroxyglutarate (r=-0.18). Metabolites of amino
      acids and amino acid degredation (indoxy sulfate; HR=1.48, 95% CI 1.09-2.03,
      symmetric dimethylarginine; HR=3.58, 95% CI=1.57-8.15, N-carbamoyl beta-alanine;
      HR=1.91, 95% CI=1.16-3.14, quinolinate; HR 2.56, 95% CI 1.65-3.96) and
      metabolites related to kidney function (aforementioned symmetric dimethylarginine
      and indoxy sulfate as well as creatinine; HR 5.91, 95% CI 2.06-16.9, inositol; HR
      2.70, 95% CI 1.47-4.97) were among the 23 metabolites associated with incident
      mobility disability. Conclusions: This study highlights the potential role of
      amino acid derivatives and products and kidney function early in the development
      of mobility disability and suggests metabolic profiles could help identify
      individuals at risk of functional decline.

PMID- 29186399
TI  - Construction of PRDM9 allele-specific recombination maps in cattle using large
      scale pedigree analysis and genome-wide single sperm genomics.
AB  - PRDM9 contributes to hybrid sterility and species evolution. However, its role is
      to be confirmed in cattle, a major domesticated livestock species. We previously
      found an association near PRDM9 with cattle recombination features, but the
      causative variants are still unknown. Using millions of genotyped cattle with
      pedigree information, we characterized five PRDM9 alleles and generated allele
      specific recombination maps. By examining allele-specific recombination patterns,
      we observed the impact of PRDM9 on global distribution of recombination,
      especially in the two ends of chromosomes. We also showed strong associations
      between recombination hotspot regions and functional mutations within PRDM9 zinc
      finger domain. More importantly, we found one allele of PRDM9 to be very
      different from others in both protein composition and recombination landscape,
      indicating the causative role of this allele on the association between PRDM9 and
      cattle recombination. When comparing recombination maps from sperm and pedigree
      data, we observed similar genome-wide recombination patterns, validating the
      quality of pedigree-based results. Collectively, these evidence supported PRDM9
      alleles as causal variants for the reported association with cattle
      recombination. Our study comprehensively surveyed the bovine PRDM9 alleles,
      generated allele-specific recombination maps, and expanded our understanding of
      the role of PRDM9 on genome distribution of recombination.

PMID- 29186401
TI  - Appropriate implantable cardioverter-defibrillator interventions in cardiac
      resynchronization therapy-defibrillator (CRT-D) patients undergoing device
      replacement: time to downgrade from CRT-D to CRT-pacemaker? Insights from real
      world clinical practice in the DECODE CRT-D analysis.
AB  - Aim: Ventricular tachycardia (VT)/ventricular fibrillation (VF) occurrence after
      cardiac resynchronization therapy-defibrillator (CRT-D) replacement is unknown;
      hence, there is no practical guideline to recommend either CRT-D or CRT-pacemaker
      at the time of device replacement. We observed the 1-year VT/VF occurrence after
      CRT-D replacement in a subanalysis of the Detect Long-term Complications after
      ICD Replacement (DECODE) registry. Methods and results: A total of 332
      consecutive patients who had undergone CRT-D replacement from 2013 to 2015 were
      enrolled in 36 Italian centres. The primary endpoint was the number of patients
      with any appropriate implantable cardioverter-defibrillator (ICD) interventions
      during 12-month follow-up. The secondary endpoint comprised death from any cause
      and appropriate ICD interventions. At replacement, 214 (64.5%) patients had a
      left ventricular ejection fraction <= 35% and 138 (41.6%) patients had a
      secondary prevention indication for ICD. Seventy (21.1%) patients had no longer
      indication to ICD therapy. During a median follow-up period of 406.5 (362-533)
      days, VT/VF requiring therapy delivery occurred in 57 (17%) patients,
      specifically in 7% of those who no longer had an ICD indication. On multivariate
      analysis, number of criteria for ICD replacement independently predicted
      appropriate ICD intervention during follow-up [hazard ratio (HR) = 1.62, 95%
      confidence interval (CI) 1.07-2.46; log-rank P = 0.02]. The combined endpoint of
      death from any cause or appropriate ICD therapy occurred in 76 (23%) patients.
      Only NYHA class remained associated with this combined endpoint (HR = 1.97, 95%
      CI 1.23-3.14; P = 0.005). Conclusions: The DECODE registry showed the 'real
      world' experience of CRT-D recipients approaching device replacement, in which 7%
      of patients who no longer had an indication for ICD therapy experienced
      appropriate ICD interventions.

PMID- 29186402
TI  - In vitro and in vivo activity of single and dual antimicrobial agents against KPC
      producing Klebsiella pneumoniae.
AB  - Objectives: Options for treatment of infections due to KPC-producing Klebsiella
      pneumoniae are limited and combination therapy is often recommended. In this
      report, the in vitro and in vivo activity of potential therapeutic agents and
      combinations was assessed against four KPC-producing K. pneumoniae isolates.
      Methods: Using clinically relevant concentrations, time-kill experiments and the
      Galleria mellonella model of infection were used to examine the activity of
      polymyxin B, ceftazidime/avibactam, meropenem, rifampicin and amikacin alone and
      in combination. Results: Two K. pneumoniae isolates were resistant to polymyxin B
      and had ceftazidime/avibactam MICs of 8/4 mg/L. When ceftazidime/avibactam was
      combined with either amikacin or meropenem, synergy was observed in vitro, and
      these combinations were associated with improved survival in the in vivo model.
      Improved survival was also observed using higher doses of ceftazidime/avibactam.
      The other two K. pneumoniae isolates were susceptible to polymyxin B and had
      lower (1/4 mg/L) MICs of ceftazidime/avibactam. For these two isolates,
      bactericidal activity was observed in vitro at ceftazidime/avibactam
      concentrations four times the MIC. At one-quarter of the MIC, synergy was
      observed when ceftazidime/avibactam was combined with meropenem. In the in vivo
      model with the two susceptible isolates, improved survival rates were observed
      following therapy with ceftazidime/avibactam monotherapy. For all four isolates,
      polymyxin B with or without rifampicin or meropenem performed poorly in the in
      vivo model. Conclusions: Pending clinical studies, combining
      ceftazidime/avibactam with another agent (e.g. a carbapenem) should be considered
      when treating serious infections due to these pathogens, particularly for
      isolates with ceftazidime/avibactam MICs near the susceptibility breakpoint.

PMID- 29186403
TI  - Associations Between Enteral Colonization With Gram-Negative Bacteria and
      Intensive Care Unit-Acquired Infections and Colonization of the Respiratory
      Tract.
AB  - Background: Enteral and respiratory tract colonization with gram-negative
      bacteria may lead to subsequent infections in critically ill patients. We aimed
      to clarify the interdependence between gut and respiratory tract colonization and
      their associations with intensive care unit (ICU)-acquired infections in patients
      receiving selective digestive tract decontamination (SDD). Methods: Colonization
      status of the rectum and respiratory tract was determined using twice-weekly
      microbiological surveillance in mechanically ventilated subjects receiving SDD
      between May 2011 and June 2015 in a tertiary medical-surgical ICU in the
      Netherlands. Acquisition of infections was monitored daily by dedicated
      observers. Marginal structural models were used to determine the associations
      between gram-negative rectal colonization and respiratory tract colonization, ICU
      acquired gram-negative infection, and ICU-acquired gram-negative bacteremia.
      Results: Among 2066 ICU admissions, 1157 (56.0%) ever had documented gram
      negative carriage in the rectum during ICU stay. Cumulative incidences of ICU
      acquired gram-negative infection and bacteremia were 6.0% (n = 124) and 2.1% (n =
      44), respectively. Rectal colonization was an independent risk factor for both
      respiratory tract colonization (cause-specific hazard ratio [CSHR], 2.93 [95%
      confidence interval {CI}, 2.02-4.23]) and new gram-negative infection in the ICU
      (CSHR, 3.04 [95% CI, 1.99-4.65]). Both rectal and respiratory tract colonization
      were associated with bacteremia (CSHR, 7.37 [95% CI, 3.25-16.68] and 2.56 [95%
      CI, 1.09-6.03], respectively). Similar associations were observed when
      Enterobacteriaceae and glucose nonfermenting gram-negative bacteria were analyzed
      separately. Conclusions: Gram-negative rectal colonization tends to be stronger
      associated with subsequent ICU-acquired gram-negative infections than gram
      negative respiratory tract colonization. Gram-negative rectal colonization seems
      hardly associated with subsequent ICU-acquired gram-negative respiratory tract
      colonization.

PMID- 29186404
TI  - The grandparent and the grandchild separated by 50 years sharing the left
      ventricular outflow tract.

PMID- 29186405
TI  - A critical re-evaluation of multilocus sequence typing (MLST) efforts in
      Wolbachia.
AB  - Wolbachia (Alphaproteobacteria, Rickettsiales) is the most common, and arguably
      one of the most important inherited symbionts. Molecular differentiation of
      Wolbachia strains is routinely performed with a set of five multilocus sequence
      typing (MLST) markers. However, since its inception in 2006, the performance of
      MLST in Wolbachia strain typing has not been assessed objectively. Here, we
      evaluate the properties of Wolbachia MLST markers and compare it to 252 other
      single copy loci present in the genome of most Wolbachia strains. Specifically,
      we investigated how well MLST performs at strain differentiation, at reflecting
      genetic diversity of strains, and as phylogenetic marker. We find that MLST loci
      are outperformed by other loci at all tasks they are currently employed for, and
      thus that they do not reflect the properties of a Wolbachia strain very well. We
      argue that whole genome typing approaches should be used for Wolbachia typing in
      the future. Alternatively, if few loci approaches are necessary, we provide a
      characterisation of 252 single copy loci for a number a criteria, which may
      assist in designing specific typing systems or phylogenetic studies.

PMID- 29186406
TI  - Corrigendum to: Chronic refractory angina pectoris: recent progress and remaining
      challenges.

PMID- 29186407
TI  - Surgical ablation of atrial fibrillation: a systematic review and meta-analysis
      of randomized controlled trials.
AB  - Aims: The aim of this review was to assess the effect of concomitant surgical
      atrial fibrillation (AF) ablation on postoperative freedom from AF and patient
      important outcomes. Methods and results: We searched Cochrane CENTRAL, MEDLINE,
      and EMBASE databases from inception to May 2016 for randomized controlled trials
      (RCTs) evaluating surgical AF ablation using any lesion set vs. no surgical AF
      ablation in adults with AF undergoing cardiac surgery. We performed screening,
      risk-of-bias evaluation, and data collection independently and in duplicate. We
      evaluated risk of bias with the modified Cochrane tool, quality of evidence using
      GRADE framework, and pooled data with a random-effects model. Of the 23 included
      studies, only one was considered at low risk of bias. Surgical AF ablation was
      associated with more freedom from AF at 12 months [relative risk (RR) = 2.32, 95%
      confidence interval (CI) 1.92-2.80; P < 0.001, low quality]. However, no
      significant difference was seen in mortality (RR = 1.07, 95% CI 0.72-1.52; P =
      0.41, moderate quality), stroke (RR = 1.19, 95% CI 0.59-2.39; P = 0.63, moderate
      quality), or pacemaker implantation (RR = 1.28, 95% CI 0.85-1.95; P = 0.24, high
      quality). Comparing biatrial and left-sided lesion sets showed no difference in
      mortality (P-interaction = 0.60) or stroke (P-interaction = 0.12). At 12 months,
      biatrial procedures led to more freedom from AF (RR = 2.80, 95% CI 2.13-3.68; P <
      0.0001) when compared with left-sided ablation (RR = 2.00, 95% CI 1.68-2.39; P <
      0.0001) (P-interaction = 0.04) Biatrial procedures appear to increase the risk
      for pacemaker (RR = 2.68, 95% CI 1.41-5.11; P = 0.002) compared with no ablation
      while left-sided ablation does not (RR = 1.08, 95% CI 0.67-1.74; P = 0.76) (P
      interaction = 0.03). Conclusion: Surgical AF ablation during cardiac surgery
      improves freedom from AF. However, impact on patient-important outcomes including
      mortality and stroke has not shown statistical significance in current RCT
      evidence. Biatrial compared with left-sided lesion sets showed no difference in
      mortality or stroke but were associated with significantly increased freedom from
      AF and risk for pacemaker requirement.

PMID- 29186408
TI  - A significant therapeutic effect of immunoglobulins administered alone, or in
      combination with conventional chemotherapy, in experimental pulmonary
      tuberculosis caused by drug-sensitive or drug-resistant strains.
AB  - The recommended chemotherapy for drug-sensitive tuberculosis (TB) consists of
      four different antibiotics administrated for 6 months. This long treatment leads
      to significant compliance problems and consequently to recrudescence of the
      disease and to the development of multidrug-resistant (MDR) strains. Thus, new
      alternatives are needed to shorten or simplify the treatment of TB. Antibodies
      have therapeutic effects in animal models of TB, so their use as adjuvants in
      drug-sensitive and MDR TB is an interesting alternative. To assess the effect of
      antibodies, BALB/c mice with active late disease 60 days after infection with
      drug-sensitive TB strain H37Rv were treated with intravenous immunoglobulin
      (IVIg), alone or in combination with conventional chemotherapy. When compared
      with control non-treated animals, IVIg alone produced a significantly decreased
      burden of pulmonary bacilli. This decrease was even greater when IVIg was used in
      combination with conventional chemotherapy. The combined therapy also
      significantly reduced tissue damage (pneumonia) when compared to infected animals
      treated only with antibiotics. IVIg treatment also caused decreased bacillary
      burdens in mice infected with an MDR strain. In vitro experiments suggested that
      improving phagocytosis by efficient opsonization is perhaps the principal
      mechanism of this beneficial therapeutic effect.

PMID- 29186409
TI  - Dynamic J-point elevation associated with bigeminy in a patient with early
      repolarization phenotype.

PMID- 29186410
TI  - Induction of a viable but non-culturable state in Salmonella Typhimurium by
      thermosonication and factors affecting resuscitation.
AB  - The objective of this work was to analyze the effects of thermosonication (TS) on
      induction of a viable but non-culturable (VBNC) state in Salmonella Typhimurium
      and to examine incubation factors affecting subsequent resuscitation of cells. A
      TS treatment of 380 W at 53 degrees C for 30 min induced the VBNC state in S.
      Typhimurium cells in beef peptone yeast (BPY) broth, apple/carrot juice,
      physiological saline and phosphate buffer solution. The logarithmic and decline
      phases of growth were more sensitive to the TS treatment compared to stationary
      phase cells. Meanwhile, VBNC S. Typhimurium could be resuscitated back to
      culturable cells by using suitable incubation temperatures and media. Addition of
      Tween 20 hindered resuscitation compared to the use of BPY medium alone. The
      optimal growth temperature (i.e. 37 degrees C) was the most suitable temperature
      to resuscitate cells from the VBNC state. The VBNC incidence index decreased with
      the addition of sodium pyruvate during TS treatment, as it accelerated
      resuscitation. The results demonstrated that free radicals produced during TS
      processing and the growth phase of cells affected induction of the VBNC state in
      S. Typhimurium. Hence, the kinds and amounts of free radicals generated during TS
      treatment should be analyzed in the future.

PMID- 29186411
TI  - Late onset of pneumothorax after bronchoscopic lung volume reduction due to
      migration of a nitinol coil.
AB  - The use of Endobronchial coils are a relatively new brochoscopic technique for
      lung volume reduction. They appear to be safe and effective in improving quality
      of life, reducing morbidity and mortality related to the primary disease, while
      avoiding the many risks of morbidity and mortality associated with surgery.
      Nevertheless, some complications, such as pneumothorax, are relatively common in
      the periprocedural period. We describe a case of pneumothorax that occurred
      several days after brochoscopic technique for lung volume reduction due to direct
      perforation of the visceral pleura by a coil. The patient presented with a large
      pneumothorax associated with significant air leak, requiring surgical
      intervention. Exploration of the chest cavity showed a pleural tear caused by a
      coil. To our knowledge, this is an adverse event that has never been described
      before, suggesting the possible migration of the coil from the original position.

PMID- 29186412
TI  - Genomic characterization and comparative analysis of Leptospira interrogans
      serogroup Australis isolated from swine.
AB  - The Leptospira interrogans serogroup Australis is traditionally described as
      pathogenic for swine although animals usually present low serologic response and
      mild clinical signs. The first isolation of a Leptospira interrogans serogroup
      Australis strain from swine, in Brazil, was recently described. Herein we present
      the genomic characterization of this strain (SU5) and further comparison with the
      Leptospira serovars reference genomes available in the GenBank database. The SU5
      strain was characterized with sequence types previously described in a serogroup
      Australis isolated from human and presented a new ST98 that is thus far
      exclusively of the Brazilian porcine L. interrogans serogroup Australis. Even
      though the SU5 strain presented higher similarity with the American porcine
      serogroup Australis strain PigK151, as expected, it also presented sequences
      blocks in both chromosomes which are absent in the genomes of the studied
      Leptospira serovars. These regions are flanked by insertion sequences and
      transposases genes, suggesting the existence of inter- and intra-serogroup
      genomic variability due to mobile elements transferring. This genomic plasticity
      has already been demonstrated for pathogenic Leptospira species; nevertheless,
      there is still a limited understanding of the relationship between genome
      organization and content and the divergence of Leptospira serogroups and serovars
      that needs to be further elucidated.

PMID- 29186413
TI  - Antenatal paternal adjustment and paternal attitudes after infertility treatment.
AB  - STUDY QUESTION: Do mode of conception [ART versus Natural (NC)] and depression
      have an interactive effect on antenatal paternal adjustment and paternal
      attitudes? SUMMARY ANSWER: Depression increased the negative effect of ART on
      antenatal paternal adjustment and paternal attitudes, specifically on antenatal
      marital relationship satisfaction. WHAT IS KNOWN ALREADY: Research on antenatal
      paternal adjustment and paternal attitudes after ART is scarce and has produced
      inconsistent results. STUDY DESIGN, SIZE, DURATION: This cross-sectional study
      assessed 197 primiparous men (71 ART and 126 NC) during their partner's second
      trimester of gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants
      were derived from three larger longitudinal studies recruited at public Health
      Services in Northern Portugal. All men, for who this was their first child and
      had filled in a socio-demographic questionnaire, measures of depression and
      anxiety, and antenatal paternal adjustment and paternal attitudes were selected.
      MAIN RESULTS AND THE ROLE OF CHANCE: An interaction effect of mode of conception
      and depression was found on antenatal paternal adjustment and paternal attitudes.
      ART men showing high depressive symptomatology had lower antenatal marital
      relationship satisfaction than ART men showing low depressive symptomatology and
      NC men showing high or low depressive symptomatology. LIMITATIONS, REASONS FOR
      CAUTION: Due to the cross-sectional design of this study and the small sample
      size in the depression groups, the findings should be interpreted with caution.
      WIDER IMPLICATIONS OF THE FINDINGS: Specialized psychological support should be
      available for ART men screened with high depressive symptomatology as part of
      routine prenatal care appointments. STUDY FUNDING/COMPETING INTEREST(S): This
      study was conducted at Psychology Research Centre (UID/PSI/ 01662/2013),
      University of Minho, and at the Unidade de Investigacao em Epidemiologia
      Instituto de Saude Publica da Universidade do Porto (EPIUnit)
      (UID/DTP/04750/2013). It was supported by the Foundation for Science and
      Technology (Portuguese Ministry of Education and Science) through National funds
      and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership
      Agreement (POCI-01-0145-FEDER-007653) and through the Operational Programme
      Factors of Competitiveness-COMPETE within the project 'Health, Governance and
      Accountability in Embryo Research: Couples' Decisions About the Fates of Embryos'
      (FCOMP-01-0124-FEDER-014453), the FCT Investigator contract IF/01674/2015 and PhD
      grants (SFRH/BD/115048/2016, SFRH/BD/75807/2011 and SFRH/BD/40146/2007). The
      authors have no conflicts of interest.

PMID- 29186415
TI  - Atrioventricular dromotropathy: evidence for a distinctive entity in heart
      failure with prolonged PR interval?
AB  - Heart failure (HF) is often accompanied by atrioventricular (AV) conduction
      disturbance, represented by prolongation of the PR interval on the
      electrocardiogram. Studies suggest that PR prolongation exists in at least 10% of
      HF patients, and it seems more prevalent in the presence of prolonged QRS
      duration. A prolonged PR interval may result in elevated left ventricular (LV)
      end-diastolic pressure, diastolic mitral regurgitation, and reduced LV pump
      function. This seems especially the case in patients with heart disease, in whom
      it is associated with an increased risk for atrial fibrillation, advanced AV
      heart block, HF, and death. These findings point towards the importance of proper
      AV coupling in HF patients. A few studies, strongly differing in design, suggest
      that restoration of AV coupling in patients with PR prolongation by pacing
      improves cardiac function and clinical outcomes. These observations argue for AV
      dromotropathy as a potential target for pacing therapy, but other studies show
      inconsistent results. Given its potential clinical implications, restoration of
      AV coupling by pacing warrants further investigation. Additional possible future
      research goals include assessing different techniques to measure compromised AV
      coupling, determine the best site(s) of ventricular pacing, and assess a
      potential influence of diastolic mitral regurgitation in the efficacy of such
      therapy.

PMID- 29186414
TI  - Local sympathetic denervation attenuates myocardial inflammation and improves
      cardiac function after myocardial infarction in mice.
AB  - Aims: Cardiac inflammation has been suggested to be regulated by the sympathetic
      nervous system (SNS). However, due to the lack of methodology to surgically
      eliminate the myocardial SNS in mice, neuronal control of cardiac inflammation
      remains ill-defined. Here, we report a procedure for local cardiac sympathetic
      denervation in mice and tested its effect in a mouse model of heart failure post
      myocardial infarction. Methods and results: Upon preparation of the carotid
      bifurcation, the right and the left superior cervical ganglia were localized and
      their pre- and postganglionic branches dissected before removal of the ganglion.
      Ganglionectomy led to an almost entire loss of myocardial sympathetic innervation
      in the left ventricular anterior wall. When applied at the time of myocardial
      infarction (MI), cardiac sympathetic denervation did not affect acute myocardial
      damage and infarct size. In contrast, cardiac sympathetic denervation
      significantly attenuated chronic consequences of MI, including myocardial
      inflammation, myocyte hypertrophy, and overall cardiac dysfunction. Conclusion:
      These data suggest a critical role for local sympathetic control of cardiac
      inflammation. Our model of myocardial sympathetic denervation in mice should
      prove useful to further dissect the molecular mechanisms underlying cardiac
      neural control.

PMID- 29186416
TI  - A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic
      Stress Disorder.
AB  - Background: Anxiety and trauma-related disorders are among the most prevalent and
      disabling medical conditions in the United States, and posttraumatic stress
      disorder in particular exacts a tremendous public health toll. We examined the
      tolerability and anxiolytic efficacy of neuropeptide Y administered via an
      intranasal route in patients with posttraumatic stress disorder. Methods: Twenty
      six individuals were randomized in a cross-over, single ascending dose study into
      1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6
      mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate
      treatment days 1 week apart in random order under double-blind conditions.
      Assessments were conducted at baseline and following a trauma script symptom
      provocation procedure subsequent to dosing. Occurrence of adverse events
      represented the primary tolerability outcome. The difference between treatment
      conditions on anxiety as measured by the Beck Anxiety Inventory and the State
      Trait Anxiety Inventory immediately following the trauma script represented
      efficacy outcomes. Results: Twenty-four individuals completed both treatment
      days. Neuropeptide Y was well tolerated up to and including the highest dose.
      There was a significant interaction between treatment and dose; higher doses of
      neuropeptide Y were associated with a greater treatment effect, favoring
      neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038).
      There was no significant interaction for State-Trait Anxiety Inventory score.
      Conclusions: Our study suggests that a single dose of neuropeptide Y is well
      tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future
      studies exploring the safety and efficacy of neuropeptide Y in stress-related
      disorders are warranted. The reported study is registered at:
      http://clinicaltrials.gov (ID: NCT01533519).

PMID- 29186417
TI  - Examining influences on speaking up among critical care healthcare providers in
      the United Arab Emirates.
AB  - Objective: Assess perceived barriers to speaking up and to provide
      recommendations for reducing barriers to reporting adverse events and near
      misses. Design, setting, participants, intervention: A six-item survey was
      administered to critical care providers in 19 Intensive Care Units in Abu Dhabi
      as part of an organizational safety and quality improvement effort. Main outcome
      measures: Questions elicited perspectives about influences on reporting,
      perceived barriers and recommendations for conveying patient safety as an
      organizational priority. Qualitative thematic analyses were conducted for open
      ended questions. Results: A total of 1171 participants were invited to complete
      the survey and 639 responded (response rate = 54.6%). Compared to other
      stakeholders (e.g. the media, public), a larger proportion of respondents
      'agreed/strongly agreed' that corporate health system leadership and the health
      regulatory authority encouraged and supported error reporting (83%; 75%), and had
      the most influence on their decisions to report (81%; 74%). 29.5% of respondents
      cited fear of repercussion as a barrier, and 21.3% of respondents indicated no
      barriers to reporting. Barriers included perceptions of a culture of blame and
      issues with reporting procedures. Recommendations to establish patient safety as
      an organizational priority included creating supportive environments to discuss
      errors, hiring staff to advocate for patient safety, and implementing policies to
      standardize clinical practices and streamline reporting procedures. Conclusions:
      Influences on reporting perceived by providers in the UAE were similar to those
      in the US and other countries. These findings highlight the roles of corporate
      leadership and regulators in developing non-punitive environments where reporting
      is a valuable and safe activity.

PMID- 29186420
TI  - Corrigendum to: 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- 29186418
TI  - Genome sequence of the Japanese oak silk moth, Antheraea yamamai: the first draft
      genome in the family Saturniidae.
AB  - Background: Antheraea yamamai, also known as the Japanese oak silk moth, is a
      wild species of silk moth. Silk produced by A. yamamai, referred to as tensan
      silk, shows different characteristics such as thickness, compressive elasticity,
      and chemical resistance compared with common silk produced from the domesticated
      silkworm, Bombyx mori. Its unique characteristics have led to its use in many
      research fields including biotechnology and medical science, and the scientific
      as well as economic importance of the wild silk moth continues to gradually
      increase. However, no genomic information for the wild silk moth, including A.
      yamamai, is currently available. Findings: In order to construct the A. yamamai
      genome, a total of 147G base pairs using Illumina and Pacbio sequencing platforms
      were generated, providing 210-fold coverage based on the 700-Mb estimated genome
      size of A. yamamai. The assembled genome of A. yamamai was 656 Mb (>2 kb) with
      3675 scaffolds, and the N50 length of assembly was 739 Kb with a 34.07% GC ratio.
      Identified repeat elements covered 37.33% of the total genome, and the
      completeness of the constructed genome assembly was estimated to be 96.7% by
      Benchmarking Universal Single-Copy Orthologs v2 analysis. A total of 15 481 genes
      were identified using Evidence Modeler based on the gene prediction results
      obtained from 3 different methods (ab initio, RNA-seq-based, known-gene-based)
      and manual curation. Conclusions: Here we present the genome sequence of A.
      yamamai, the first genome sequence of the wild silk moth. These results provide
      valuable genomic information, which will help enrich our understanding of the
      molecular mechanisms relating to not only specific phenotypes such as wild silk
      itself but also the genomic evolution of Saturniidae.

PMID- 29186419
TI  - Management of ventricular tachycardia in the ablation era: results of the
      European Heart Rhythm Association Survey.
AB  - Patients with sustained ventricular tachycardia (VT) are at risk of sudden death.
      Treatment options for VT include antiarrhythmic drug therapy, insertion of an
      implantable cardioverter-defibrillator, and catheter ablation. Evidence on
      indications for VT ablation, timing, ablation strategies, and periprocedural
      management is sparse. The aim of this European Heart Rhythm Association (EHRA)
      survey was to evaluate clinical practice regarding management of VT among the
      European countries. An electronic questionnaire was sent to members of the EHRA
      Electrophysiology Research Network. Responses were received from 88 centres in 12
      countries. The results have shown that management of VTs is very heterogeneous
      across the participating centres. Indications, periprocedural management, and
      ablation strategies vary substantially. This EP Wire survey has revealed that
      catheter ablation is the first-line therapy for the treatment of recurrent
      monomorphic stable VT in patients without structural heart disease as well as in
      patients with ischaemic cardiomyopathy and impaired left ventricular ejection
      fraction in the majority of centres. Furthermore, in patients with ischaemic
      cardiomyopathy and the first episode of monomorphic VT, most centres (62.0%)
      performed catheter ablation. On the contrary, in patients with non-ischaemic
      cardiomyopathy, amiodarone (41.4%) and catheter ablation (37.1%) are used in a
      very similar proportion. Ablation strategies, endpoints, and post-ablation
      antithrombotic management vary substantially among European centres.

PMID- 29186421
TI  - Expanding Hospital Human Immunodeficiency Virus Testing in the Bronx, New York
      and Washington, District of Columbia: Results From the HPTN 065 Study.
AB  - Background: Human immunodeficiency virus (HIV) testing is critical for both HIV
      treatment and prevention. Expanding testing in hospital settings can identify
      undiagnosed HIV infections. Methods: To evaluate the feasibility of universally
      offering HIV testing during emergency department (ED) visits and inpatient
      admissions, 9 hospitals in the Bronx, New York and 7 in Washington, District of
      Columbia (DC) undertook efforts to offer HIV testing routinely. Outcomes included
      the percentage of encounters with an HIV test, the change from year 1 to year 3,
      and the percentages of tests that were HIV-positive and new diagnoses. Results:
      From 1 February 2011 to 31 January 2014, HIV tests were conducted during 6.5% of
      1621016 ED visits and 13.0% of 361745 inpatient admissions in Bronx hospitals and
      13.8% of 729172 ED visits and 22.0% of 150655 inpatient admissions in DC. From
      year 1 to year 3, testing was stable in the Bronx (ED visits: 6.6% to 6.9%;
      inpatient admissions: 13.0% to 13.6%), but increased in DC (ED visits: 11.9% to
      15.8%; inpatient admissions: 19.0% to 23.9%). In the Bronx, 0.4% (408) of ED HIV
      tests were positive and 0.3% (277) were new diagnoses; 1.8% (828) of inpatient
      tests were positive and 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED
      tests were positive and 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient
      tests were positive and 0.7% (189) were new diagnoses. Conclusions: Hospitals
      consistently identified previously undiagnosed HIV infections, but universal
      offer of HIV testing proved elusive.

PMID- 29186422
TI  - Cohort Profile: The Korean Cancer Prevention Study-II (KCPS-II) Biobank.

PMID- 29186424
TI  - NALT M cells are important for immune induction for the common mucosal immune
      system.
AB  - Nasopharynx-associated lymphoid tissue (NALT) is one of the major constituents of
      the mucosa-associated lymphoid tissue (MALT), and has the ability to induce
      antigen-specific immune responses. However, the molecular mechanisms responsible
      for antigen uptake from the nasal cavity into the NALT remain largely unknown.
      Immunohistochemical analysis showed that CCL9 and CCL20 were co-localized with
      glycoprotein 2 (GP2) in the epithelium covering NALT, suggesting the existence of
      M cells in NALT. In analogy with the reduced number of Peyer's patch M cells in
      CCR6-deficient mice, the number of NALT M cells was drastically decreased in CCR6
      deficient mice compared with the wild-type mice. Translocation of nasally
      administered Salmonella enterica serovar Typhimurium into NALT via NALT M cells
      was impaired in CCR6-deficient mice, whereas S. Typhimurium demonstrated
      consistent co-localization with NALT M cells in wild-type mice. When wild-type
      mice were nasally administered with an attenuated vaccine strain of S.
      Typhimurium, the mice were protected from a subsequent challenge with wild-type
      S. Typhimurium. Antigen-specific fecal and nasal IgA was detected after nasal
      immunization with the attenuated vaccine strain of S. Typhimurium only in wild
      type mice but not in CCR6-deficient mice. Taken together, these observations
      demonstrate that NALT M cells are important as a first line of defense against
      infection by enabling activation of the common mucosal immune system (CMIS).

PMID- 29186423
TI  - Improving amphibian genomic resources: a multitissue reference transcriptome of
      an iconic invader.
AB  - Background: Cane toads (Rhinella marina) are an iconic invasive species
      introduced to 4 continents and well utilized for studies of rapid evolution in
      introduced environments. Despite the long introduction history of this species,
      its profound ecological impacts, and its utility for demonstrating evolutionary
      principles, genetic information is sparse. Here we produce a de novo
      transcriptome spanning multiple tissues and life stages to enable investigation
      of the genetic basis of previously identified rapid phenotypic change over the
      introduced range. Findings: Using approximately 1.9 billion reads from developing
      tadpoles and 6 adult tissue-specific cDNA libraries, as well as a transcriptome
      assembly pipeline encompassing 100 separate de novo assemblies, we constructed 62
      202 transcripts, of which we functionally annotated ~50%. Our transcriptome
      assembly exhibits 90% full-length completeness of the Benchmarking Universal
      Single-Copy Orthologs data set. Robust assembly metrics and comparisons with
      several available anuran transcriptomes and genomes indicate that our cane toad
      assembly is one of the most complete anuran genomic resources available.
      Conclusions: This comprehensive anuran transcriptome will provide a valuable
      resource for investigation of genes under selection during invasion in cane
      toads, but will also greatly expand our general knowledge of anuran genomes,
      which are underrepresented in the literature. The data set is publically
      available in NCBI and GigaDB to serve as a resource for other researchers.

PMID- 29186425
TI  - Conventional and hyperspectral time-series imaging of maize lines widely used in
      field trials.
AB  - Background: Maize (Zea mays ssp. mays) is 1 of 3 crops, along with rice and
      wheat, responsible for more than one-half of all calories consumed around the
      world. Increasing the yield and stress tolerance of these crops is essential to
      meet the growing need for food. The cost and speed of plant phenotyping are
      currently the largest constraints on plant breeding efforts. Datasets linking new
      types of high-throughput phenotyping data collected from plants to the
      performance of the same genotypes under agronomic conditions across a wide range
      of environments are essential for developing new statistical approaches and
      computer vision-based tools. Findings: A set of maize inbreds-primarily recently
      off patent lines-were phenotyped using a high-throughput platform at University
      of Nebraska-Lincoln. These lines have been previously subjected to high-density
      genotyping and scored for a core set of 13 phenotypes in field trials across 13
      North American states in 2 years by the Genomes 2 Fields Consortium. A total of
      485 GB of image data including RGB, hyperspectral, fluorescence, and thermal
      infrared photos has been released. Conclusions: Correlations between image-based
      measurements and manual measurements demonstrated the feasibility of quantifying
      variation in plant architecture using image data. However, naive approaches to
      measuring traits such as biomass can introduce nonrandom measurement errors
      confounded with genotype variation. Analysis of hyperspectral image data
      demonstrated unique signatures from stem tissue. Integrating heritable phenotypes
      from high-throughput phenotyping data with field data from different environments
      can reveal previously unknown factors that influence yield plasticity.

PMID- 29186426
TI  - The liver receptor homolog-1 (LRH-1) is expressed in human islets and protects
      beta-cells against stress-induced apoptosis.

PMID- 29186427
TI  - Insulinlike Growth Factor-Binding Protein-1 Improves Vascular Endothelial Repair
      in Male Mice in the Setting of Insulin Resistance.
AB  - Insulin resistance is associated with impaired endothelial regeneration in
      response to mechanical injury. We recently demonstrated that insulinlike growth
      factor-binding protein-1 (IGFBP1) ameliorated insulin resistance and increased
      nitric oxide generation in the endothelium. In this study, we hypothesized that
      IGFBP1 would improve endothelial regeneration and restore endothelial reparative
      functions in the setting of insulin resistance. In male mice heterozygous for
      deletion of insulin receptors, endothelial regeneration after femoral artery wire
      injury was enhanced by transgenic expression of human IGFBP1 (hIGFBP1). This was
      not explained by altered abundance of circulating myeloid angiogenic cells.
      Incubation of human endothelial cells with hIGFBP1 increased integrin expression
      and enhanced their ability to adhere to and repopulate denuded human saphenous
      vein ex vivo. In vitro, induction of insulin resistance by tumor necrosis factor
      alpha (TNFalpha) significantly inhibited endothelial cell migration and
      proliferation. Coincubation with hIGFBP1 restored endothelial migratory and
      proliferative capacity. At the molecular level, hIGFBP1 induced phosphorylation
      of focal adhesion kinase, activated RhoA and modulated TNFalpha-induced actin
      fiber anisotropy. Collectively, the effects of hIGFBP1 on endothelial cell
      responses and acceleration of endothelial regeneration in mice indicate that
      manipulating IGFBP1 could be exploited as a putative strategy to improve
      endothelial repair in the setting of insulin resistance.

PMID- 29186428
TI  - Genome-wide meta-analysis identifies novel determinants of circulating serum
      progranulin.
AB  - Progranulin is a secreted protein with important functions in processes including
      immune and inflammatory response, metabolism and embryonic development. The
      present study aimed at identification of genetic factors determining progranulin
      concentrations. We conducted a genome-wide association meta-analysis for serum
      progranulin in three independent cohorts from Europe: Sorbs (N = 848) and KORA (N
      = 1628) from Germany and PPP-Botnia (N = 335) from Finland (total N = 2811).
      Single nucleotide polymorphisms (SNPs) associated with progranulin levels were
      replicated in two additional German cohorts: LIFE-Heart Study (Leipzig; N = 967)
      and Metabolic Syndrome Berlin Potsdam (Berlin cohort; N = 833). We measured mRNA
      expression of genes in peripheral blood mononuclear cells (PBMC) by micro-arrays
      and performed mRNA expression quantitative trait and expression-progranulin
      association studies to functionally substantiate identified loci. Finally, we
      conducted siRNA silencing experiments in vitro to validate potential candidate
      genes within the associated loci. Heritability of circulating progranulin levels
      was estimated at 31.8% and 26.1% in the Sorbs and LIFE-Heart cohort,
      respectively. SNPs at three loci reached study-wide significance (rs660240 in
      CELSR2-PSRC1-MYBPHL-SORT1, rs4747197 in CDH23-PSAP and rs5848 in GRN) explaining
      19.4%/15.0% of the variance and 61%/57% of total heritability in the Sorbs/LIFE
      Heart Study. The strongest evidence for association was at rs660240 (P = 5.75 *
      10-50), which was also associated with mRNA expression of PSRC1 in PBMC (P = 1.51
      * 10-21). Psrc1 knockdown in murine preadipocytes led to a consecutive 30%
      reduction in progranulin secretion. In conclusion, the present meta-GWAS combined
      with mRNA expression identified three loci associated with progranulin and
      supports the role of PSRC1 in the regulation of progranulin secretion.

PMID- 29186429
TI  - Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for
      future therapeutics.
AB  - BACKGROUND: Uterine leiomyoma (also known as fibroid or myoma) is the most common
      benign tumor of the uterus found in women of reproductive age. It is not usually
      fatal but can produce serious clinical symptoms, including excessive uterine
      bleeding, pelvic pain or pressure, infertility and pregnancy complications. Due
      to lack of effective medical treatments surgery has been a definitive choice for
      the management of this tumor. OBJECTIVE AND RATIONALE: Extracellular matrix (ECM)
      accumulation and remodeling are thought to be crucial for fibrotic diseases such
      as uterine leiomyoma. Indeed, ECM plays important role in forming the bulk
      structure of leiomyoma, and the ECM-rich rigid structure within these tumors is
      thought to be a cause of abnormal bleeding and pelvic pain. Therefore, a better
      understanding of ECM accumulation and remodeling is critical for developing new
      therapeutics for uterine leiomyoma. SEARCH METHODS: PubMed and Google Scholar
      were searched for all original and review articles/book chapters related to ECM
      and medical treatments of uterine leiomyoma published in English until May 2017.
      OUTCOMES: This review discusses the involvement of ECM in leiomyoma pathogenesis
      as well as current and future medical treatments that target ECM directly or
      indirectly. Uterine leiomyoma is characterized by elevated levels of collagens,
      fibronectin, laminins and proteoglycans. They can induce the mechanotransduction
      process, such as activation of the integrin-Rho/p38 MAPK/ERK pathway, resulting
      in cellular responses that are involved in pathogenesis and altered bidirectional
      signaling between leiomyoma cells and the ECM. ECM accumulation is affected by
      growth factors (TGF-beta, activin-A and PDGF), cytokines (TNF-alpha), steroid
      hormones (estrogen and progesterone) and microRNAs (miR-29 family, miR-200c and
      miR-93/106b). Among these, TGF-betas (1 and 3) and activin-A have been suggested
      as key players in the accumulation of excessive ECM (fibrosis) in leiomyoma. The
      presence of elevated levels of ECM and myofibroblasts in leiomyoma supports the
      fibrotic character of these tumors. Interestingly, ECM may serve as a reservoir
      of profibrotic growth factors and enhance their activity by increasing their
      stability and extending their duration of signaling. At present, several classes
      of compounds, including gonadotropin-releasing hormone (GnRH) agonist (leuprolide
      acetate), GnRH antagonist (cetrorelix acetate), selective progesterone receptor
      modulators (ulipristate acetate and asoprisnil), antiprogestin (mifepristone) and
      natural compounds like vitamin D and resveratrol have been studied as medical
      treatments that target ECM in uterine leiomyoma. WIDER IMPLICATIONS: Although
      several types of drugs (mostly antiproliferative agents) are available for
      leiomyoma treatment, none of them were introduced specifically as antifibrotic
      agents. In light of its critical role in the process of fibrosis in leiomyoma, we
      propose that ECM should be considered as a crucial target for future
      therapeutics. Thus, the introduction of drugs that are specifically antifibrotic
      could be a good solution to control abnormal leiomyoma growth and associated
      clinical symptoms. The antifibrotic compounds can be introduced based on their
      ability to regulate ECM components and their receptors, as well as growth
      factors, cytokines, steroid hormones and their corresponding receptors and
      intracellular signaling pathways, as well as microRNAs, involved in ECM
      production in leiomyoma.

PMID- 29186430
TI  - The effects of fungal root endophytes on plant growth are stable along gradients
      of abiotic habitat conditions.
AB  - Plant symbioses with fungal root endophytes span a continuum from mutualistic to
      parasitic outcomes, and are highly variable depending on the genotype of each
      symbiont. The abiotic context in which interactions occur also seems to influence
      the outcome of plant-endophyte symbioses, but we lack understanding of its
      relative importance. We aimed to assess if changes in abiotic variables determine
      the effects of fungal root endophytes on plant growth. We used in vitro co
      cultivation assays to test the impact of a selection of endophytic strains from
      diverse lineages on the growth of Arabidopsis thaliana, Microthlaspi erraticum
      and Hordeum vulgare along gradients of nutrient availability, light intensity or
      substrate pH. Most fungi showed a negative but weak effect on plant growth,
      whereas only a few had persistent detrimental effects across plants and
      conditions. Changes in abiotic factors affected plant growth but had little
      influence on their response to fungal inoculation. Of the factors tested,
      variation in nutrient availability resulted in the most variable plant-endophyte
      interactions, although changes were feeble and strain-specific. Our findings
      suggest that the effects of root endophytes on plant growth are robust to changes
      in the abiotic environment when these encompass the tolerance range of either
      symbiont.

PMID- 29186432
TI  - Bacterial zincophore [S,S]-ethylenediamine-N,N'-disuccinic acid is an effective
      inhibitor of MBLs.
AB  - Objectives: Carbapenemases such as MBLs are spreading among Gram-negative
      bacterial pathogens. Infections due to these MDR bacteria constitute a major
      global health challenge. Therapeutic strategies against carbapenemase-producing
      bacteria include beta-lactamase inhibitor combinations. [S,S]-ethylenediamine
      N,N'-disuccinic acid (EDDS) is a chelator and potential inhibitor of MBLs. We
      investigated the activity of EDDS in combination with imipenem against MBL
      producing bacteria in vitro as well as in vivo. Methods: The inhibitory activity
      of EDDS was analysed by means of a fluorescence-based assay using purified
      recombinant MBLs, i.e. NDM-1, VIM-1, SIM-1 and IMP-1. The in vitro activity of
      imipenem +/- EDDS against mutants as well as clinical isolates expressing MBLs
      was evaluated by broth microdilution assay. The in vivo activity of imipenem +/-
      EDDS was analysed in a Galleria mellonella infection model. Results: EDDS
      revealed potent MBL inhibitory activity against purified NDM-1, weaker activity
      against VIM-1 and SIM-1, and marginal activity against IMP-1. EDDS did not
      exhibit any intrinsic antibacterial activity, but enabled a concentration
      dependent potentiation of imipenem against mutants as well as clinical isolates
      expressing various MBLs. The in vivo model showed a significantly better survival
      rate for imipenem + EDDS-treated G. mellonella larvae infected with NDM-1
      producing Klebsiella pneumoniae compared with monotherapy with imipenem.
      Conclusions: The bacterial natural zincophore EDDS is a potent MBL inhibitor and
      in combination with imipenem overcomes MBL-mediated carbapenem resistance in
      vitro and in vivo.

PMID- 29186433
TI  - Baseline Susceptibility of Striacosta albicosta (Lepidoptera: Noctuidae) in
      Ontario, Canada to Vip3A Bacillus thuringiensis Protein.
AB  - Striacosta albicosta (Smith; Lepidoptera: Noctuidae) is a pest of corn (Zea mays
      L.), which has recently expanded its range into Ontario, Canada. Genetically
      modified corn expressing Vip3A insecticidal protein from Bacillus thuringiensis
      is a biotechnological option for the control of S. albicosta. To support an
      insect resistance management program, we conducted a study of baseline
      susceptibility of 10-field collected S. albicosta populations in Ontario, Canada
      to Vip3A before widespread commercial adoption. Neonates were exposed to
      artificial diet overlaid with Vip3A. The LC50 ranged from 22.7 to 53.5 ng Vip3A
      cm-2. The EC50 ranged from 11.4 to 30.2 ng Vip3A cm-2. There was low inter
      population variation in susceptibility to Vip3A, which we believe represents the
      natural geographical variation in response and not variation caused by previous
      exposure to selection pressure of the Vip3A protein.

PMID- 29186431
TI  - Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress
      Disorder: First Evidence from the South Eastern Europe (SEE)-PTSD Study.
AB  - Background: Posttraumatic stress disorder is characterized by an overactive
      noradrenergic system conferring core posttraumatic stress disorder symptoms such
      as hyperarousal and reexperiencing. Monoamine oxidase A is one of the key enzymes
      mediating the turnover of noradrenaline. Here, DNA methylation of the monoamine
      oxidase A gene exonI/intronI region was investigated for the first time regarding
      its role in posttraumatic stress disorder risk and severity. Methods: Monoamine
      oxidase A methylation was analyzed via direct sequencing of sodium bisulfite
      treated DNA extracted from blood cells in a total sample of N=652 (441 male)
      patients with current posttraumatic stress disorder, patients with remitted
      posttraumatic stress disorder, and healthy probands (comparison group) recruited
      at 5 centers in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo.
      Posttraumatic stress disorder severity was measured by means of the Clinician
      Administered Posttraumatic Stress Disorder Scale and its respective subscores
      representing distinct symptom clusters. Results: In the male, but not the female
      sample, patients with current posttraumatic stress disorder displayed
      hypermethylation of 3 CpGs (CpG3=43656362; CpG12=43656514; CpG13=43656553,
      GRCh38.p2 Assembly) as compared with remitted Posttraumatic Stress Disorder
      patients and healthy probands. Symptom severity (Clinician-Administered
      Posttraumatic Stress Disorder Scale scores) in male patients with current
      posttraumatic stress disorder significantly correlated with monoamine oxidase A
      methylation. This applied particularly to symptom clusters related to
      reexperiencing of trauma (cluster B) and hyperarousal (cluster D). Conclusions:
      The present findings suggest monoamine oxidase A gene hypermethylation,
      potentially resulting in enhanced noradrenergic signalling, as a disease status
      and severity marker of current posttraumatic stress disorder in males. If
      replicated, monoamine oxidase A hypermethylation might serve as a surrogate
      marker of a hyperadrenergic subtype of posttraumatic stress disorder guiding
      personalized treatment decisions on the use of antiadrenergic agents.

PMID- 29186434
TI  - Rapid disc diffusion antibiotic susceptibility testing for Pseudomonas
      aeruginosa, Acinetobacter baumannii and Enterococcus spp.
AB  - Background: We investigated the feasibility of rapid disc diffusion antibiotic
      susceptibility testing (rAST) with reading of inhibition zones after 6 and/or 8 h
      of incubation for Enterococcus faecalis, Enterococcus faecium, Pseudomonas
      aeruginosa and Acinetobacter baumannii. In addition, we evaluated discrimination
      of resistant populations from the WT populations at early timepoints and the
      requirement for clinical breakpoint adaptations for proper interpretation of rAST
      data. Methods: In total, 815 clinical strains [E. faecalis (n = 135), E. faecium
      (n = 227), P. aeruginosa (n = 295) and A. baumannii (n = 158)] were included in
      this study. Disc diffusion plates were streaked, incubated and imaged using the
      WASPLabTM automation system. WT populations and non-WT populations were defined
      using epidemiological cut-offs. Results and conclusions: rAST at 6 and 8 h was
      possible for A. baumannii and enterococci with readability of inhibition zones
      >90%. Overall categorical agreement of rAST at 6 h with AST at 18 h was 97.2%,
      97.4% and 95.3% for E. faecalis, E. faecium and A. baumannii, respectively. With
      few exceptions, major categorization error rates were <1% for A. baumannii, and
      vancomycin-resistant E. faecium were clearly separated from the WT at 6 h. For P.
      aeruginosa the average readability of inhibition zones was 68.9% at 8 h and we
      found an overall categorical agreement of 94.8%. Adaptations of clinical
      breakpoints and/or introduction of technical buffer zones, preferably based on
      aggregated population data from various epidemiological settings, are required
      for proper interpretation of rAST.

PMID- 29186435
TI  - Vermicomposts of Different Origins Protect Tomato Plants Against the Sweetpotato
      Whitefly.
AB  - The effect of four vermicomposts, obtained from different organic sources
      (pistachio waste [PWV], date waste [DWV], cattle manure waste [CMV], and food
      waste [FWV]), as well as two chemical fertilizers (complete fertilizer [CF] and
      NPK fertilizer [NPK]) on some life history traits of the sweetpotato whitefly,
      Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) was investigated in a series
      of choice and not choice experiments. In a choice experiment, adult whiteflies
      exhibited significantly lower preference for settling and oviposition on plants
      treated with vermicomposts than those in control, CF, and NPK groups (P < 0.01),
      with better results were observed in PWV group. In no choice experiment, adult
      whiteflies laid significantly fewer eggs in PWV group in comparison with control,
      CF, and NPK groups (P < 0.01); other treatments had intermediary values.
      Fertilization had a significant effect on the preadult development time of
      sweetpotato whitefly, with the longest development times were recorded for plants
      treated with PWV (24.65 d) and FWV (22.04 d), respectively. The preadult
      mortality of sweetpotato whitefly increased significantly following
      fertilization, with the greatest mortal effects were observed in PWV (54.11%) and
      DWV (44.68%) groups, respectively. Plants fertilized with PWV had significantly
      higher phenolic content (10 mg/ml) than control (BAGA; 6.08 mg/ml), while those
      in CMV group exhibited intermediary value (7.28 mg/ml). Altogether, results of
      this study reveal both antixenosis (nonpreference) and antibiosis (decreased
      survival and prolonged development time) resistance of tomato plants mediated by
      vermicomposts. Particularly, plants treated with PWV obtained the best results in
      terms of both growth and resistance to sweetpotato whitefly.

PMID- 29186437
TI  - Dr Jeremy Fauconnier talks with Prof Goran K. Hansson.

PMID- 29186436
TI  - Transcriptome profiling of fetal Klinefelter testis tissue reveals a possible
      involvement of long non-coding RNAs in gonocyte maturation.
AB  - In humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS),
      caused by the presence of one or more extra X-chromosomes. KS patients display a
      varying adult phenotype but usually present with azoospermia due to testicular
      degeneration, which accelerates at puberty. The timing of the germ cell loss and
      whether it is caused by dysgenetic fetal development of the testes is not known.
      We investigated eight fetal KS testes and found a marked reduction in MAGE-A4
      positive pre-spermatogonia compared with testes from 15 age-matched controls,
      indicating a failure of the gonocytes to differentiate into pre-spermatogonia.
      Transcriptome analysis by RNA-sequencing of formalin-fixed, paraffin-embedded
      testes originating from four fetal KS and five age-matched controls revealed 211
      differentially expressed transcripts in the fetal KS testis. We found a
      significant enrichment of upregulated X-chromosomal transcripts and validated the
      expression of the pseudoautosomal region 1 (PAR1) gene, AKAP17A. Moreover, we
      found enrichment of long non-coding RNAs in the KS testes (e.g. LINC01569 and
      RP11-485F13.1). In conclusion, our data indicate that the testicular phenotype
      observed among adult men with KS is initiated already in fetal life by failure of
      the gonocyte differentiation into pre-spermatogonia, which could be due to
      aberrant expression of long non-coding RNAs.

PMID- 29186438
TI  - In search for novel functions of adenosine 5'-triphosphate (ATP) in the heart.

PMID- 29186439
TI  - Fighting residual cardiovascular risk in stable patients with atherosclerotic
      vascular disease: COMPASS in context.

PMID- 29186440
TI  - Editorial highlights from Cardiovascular Research.

PMID- 29186442
TI  - Additional diagnostic value of CMR to the European Society of Cardiology (ESC)
      position statement criteria in a large clinical population of patients with
      suspected myocarditis.
AB  - Aims: To determine the diagnostic yield of tissue characterization by
      cardiovascular magnetic resonance (CMR) in a large clinical population of
      patients with suspected acute myocarditis (AM) and to establish its diagnostic
      value within the 2013 European Society of Cardiology position statement criteria
      (ESC-PSC) for clinically suspected myocarditis. Methods and results: In this
      retrospective study, CMR examinations of 303 hospitalized patients referred for
      work-up of suspected AM in two tertiary referral centres were analysed. CMR was
      performed at median 7 days (interquartile range 4-20 days) after clinical
      presentation and included cine imaging, T2-weighted imaging, and late gadolinium
      enhancement. CMR images were evaluated to assign each patient to a diagnosis. By
      using non-CMR criteria only, the 2013 ESC-PSC were positive for suspected
      myocarditis in 151 patients and negative in 30. In the remaining 122 patients,
      there was insufficient information available for ESC-PSC assessment, mostly due
      to lack of coronary angiography (CAG) before the CMR examination (n = 116, 95%).
      There were no in-hospital deaths. CMR provided a diagnosis in 158 patients (52%),
      including myocarditis in 104 (34%), myocardial infarction in 44 (15%), and other
      pathology in 10 patients (3%). Non-urgent CAG (>24 h after presentation) was
      performed before the CMR examination in 85 patients, of which 20 (24%) were done
      in patients with subsequently confirmed AM, which could potentially have been
      avoided if CMR was performed first. ESC-PSC was correct in diagnosing AM before
      the CMR in 50 of the 151 patients (33%) and was correct in ruling out AM in all
      the 30 patients (100%). However, ESC-PSC provided an incorrect diagnosis of AM in
      27 of the 151 patients (18%), which was corrected by CMR through the
      identification of new cardiac disease that could explain the clinical syndrome.
      Patients with insufficient ESC-PSC information had a relatively low pre-test
      probability of coronary artery disease. In this group, CMR confirmed the
      diagnosis of AM in a relatively high percentage (44%) but still revealed
      myocardial infarction in 8% of them. Conclusion: Tissue characterization by CMR
      provided a good diagnostic yield in this large clinical population of patients
      with suspected AM. CMR provided incremental diagnostic value to the ESC-PSC by
      ruling out the diagnosis of AM on one hand and by potentially sparing AM patients
      from CAG on the other.

PMID- 29186443
TI  - Into More Thin Air: Exploring the Adaptation Extremes of Human High Altitude
      Sickness and Fitness.

PMID- 29186444
TI  - 'Keep an eye' on the heart: retinal microcirculation disarray in congestive heart
      failure.

PMID- 29186441
TI  - Imaging specific cellular glycan structures using glycosyltransferases via click
      chemistry.
AB  - Heparan sulfate (HS) is a polysaccharide fundamentally important for biologically
      activities. T/Tn antigens are universal carbohydrate cancer markers. Here, we
      report the specific imaging of these carbohydrates using a mesenchymal stem cell
      line and human umbilical vein endothelial cells (HUVEC). The staining
      specificities were demonstrated by comparing imaging of different glycans and
      validated by either removal of target glycans, which results in loss of signal,
      or installation of target glycans, which results in gain of signal. As controls,
      representative key glycans including O-GlcNAc, lactosaminyl glycans and
      hyaluronan were also imaged. HS staining revealed novel architectural features of
      the extracellular matrix (ECM) of HUVEC cells. Results from T/Tn antigen staining
      suggest that O-GalNAcylation is a rate-limiting step for O-glycan synthesis.
      Overall, these highly specific approaches for HS and T/Tn antigen imaging should
      greatly facilitate the detection and functional characterization of these
      biologically important glycans.

PMID- 29186445
TI  - Acute-Contact and Chronic-Systemic In Vivo Bioassays: Regional Monitoring of
      Susceptibility to Thiamethoxam in Soybean Aphid (Hemiptera: Aphididae)
      Populations From the North Central United States.
AB  - : The risks associated with soybean aphid, Aphis glycines Matsumura (Hemiptera:
      Aphididae), in the North Central soybean systems has fostered the adoption of
      prophylactic chemical control practices, such as planting seeds treated with
      neonicotinoid insecticides, especially thiamethoxam. Consequently, there is a
      concern that increased selection pressure imposed on the arthropod-pest complex
      by this insecticide may lead to resistance. Therefore, in vivo bioassays were
      conducted to determine the susceptibility of soybean aphid to thiamethoxam among
      North Central U.S. POPULATIONS: Concentration-mortality data were collected using
      contact glass-vial and detached-leaf systemic bioassays. The results of these
      experiments indicate that both bioassays were reliable to detect shifts in
      susceptibility between different soybean aphid clones. The LC50s of field
      populations of soybean aphid were significantly different when mortality was
      recorded in contact and systemic exposure assays. Nevertheless, the magnitude of
      the resistance ratios was consistent in both methods. In addition, a significant
      increase in the LC50 and EC50 values was observed among field populations tested
      in detached-leaf systemic bioassays. These results represent the first extensive
      efforts to identify the variability in susceptibility of soybean aphid to
      thiamethoxam in the North Central United States Therefore, our results provide a
      baseline for future assessment and contribute to a better understanding of the
      applicability of in vivo bioassays for susceptibility monitoring and resistance
      detection of soybean aphid to thiamethoxam.

PMID- 29186446
TI  - Validation of the i-STAT(r)1 Analyzer for Postmortem Vitreous Humor Electrolytes
      and Glucose Analysis.
AB  - The analytical value of vitreous humor as a specimen in postmortem forensic
      toxicology has been known for some time. Numerous medical examiner laboratories
      outsource the analysis of this important specimen for electrolyte and glucose
      measurements. This can be both time-consuming and costly. The utility of the i
      STAT(r)1 medical device to measure electrolytes and glucose in whole blood
      samples has been demonstrated for over two decades in a clinical setting through
      single-use disposable cartridges that introduce samples to the i-STAT(r)1.
      Different cartridge types allow for the analysis of various analytes including
      sodium, potassium, chloride, creatinine, urea nitrogen and glucose. With only 100
      MUL of sample, results are obtained in under 4 min. In this study, we utilized
      the i-STAT(r)1 using an alternative specimen matrix, postmortem vitreous humor
      and quantitatively determined the validity and reliability of the instrument for
      this purpose. Acceptable criterion was used for each test as suggested by the
      Scientific Working Group for Forensic Toxicology. All analytes of interest,
      except creatinine, demonstrated a percent error < +/-10% for both accuracy and
      precision studies. Drug interference and stability studies were performed with
      many of the analytes demonstrating a percent error < +/-20%. Throughout drug
      interference and stability studies, all analytes of interest were detectable
      except for potassium, which gave inconclusive results. Significant interference
      with commonly found drugs were shown for creatinine and chloride but must be
      evaluated carefully. Volume additions to ethanol spiked samples caused
      significant interference for all analytes and is considered a limitation for this
      method of analysis that requires additional studies. As vitreous humor continues
      to be used in forensic medicine to aid in diagnostic interpretation, the i
      STAT(r)1 has the potential to give accurate results in a timely and cost
      effective manner.

PMID- 29186447
TI  - Large-scale phylogenomic analysis resolves a backbone phylogeny in ferns.
AB  - Background: Ferns, originated about 360 million years ago, are the sister group
      of seed plants. Despite the remarkable progress in our understanding of fern
      phylogeny, with conflicting molecular evidence and different morphological
      interpretations, relationships among major fern lineages remain controversial.
      Results: With the aim to obtain a robust fern phylogeny, we carried out a large
      scale phylogenomic analysis using high-quality transcriptome sequencing data,
      which covered 69 fern species from 38 families and 11 orders. Both coalescent
      based and concatenation-based methods were applied to both nucleotide and amino
      acid sequences in species tree estimation. The resulting topologies are largely
      congruent with each other, except for the placement of Angiopteris fokiensis,
      Cheiropleuria bicuspis, Diplaziopsis brunoniana, Matteuccia struthiopteris,
      Elaphoglossum mcclurei, and Tectaria subpedata. Conclusions: Our result confirmed
      that Equisetales is sister to the rest of ferns, and Dennstaedtiaceae is sister
      to eupolypods. Moreover, our result strongly supported some relationships
      different from the current view of fern phylogeny, including that Marattiaceae
      may be sister to the monophyletic clade of Psilotaceae and Ophioglossaceae; that
      Gleicheniaceae and Hymenophyllaceae form a monophyletic clade sister to
      Dipteridaceae; and that Aspleniaceae is sister to the rest of the groups in
      eupolypods II. These results were interpreted with morphological traits,
      especially sporangia characters, and a new evolutionary route of sporangial
      annulus in ferns was suggested. This backbone phylogeny in ferns sets a
      foundation for further studies in biology and evolution in ferns, and therefore
      in plants.

PMID- 29186448
TI  - Hepatitis E Virus Seroprevalence and Correlates of Anti-HEV IgG Antibodies in the
      Rakai District, Uganda.
AB  - A cross-sectional study was conducted of 500 human immunodeficiency virus (HIV)
      infected adults frequency matched on age, sex, and community to 500 HIV
      uninfected individuals in the Rakai District, Uganda to evaluate seroprevalence
      of anti-hepatitis E virus (HEV) IgG antibodies. HEV seroprevalence was 47%, and 1
      HIV-infected individual was actively infected with a genotype 3 virus. Using
      modified Poisson regression, male sex (prevalence ratios [PR] = 1.247; 95%
      confidence interval [CI], 1.071-1.450) and chronic hepatitis B virus infection
      (PR = 1.377; 95% CI, 1.090-1.738) were associated with HEV seroprevalence. HIV
      infection status (PR = 0.973; 95% CI, 0.852-1.111) was not associated with HEV
      seroprevalence. These data suggest there is a large burden of prior exposure to
      HEV in rural Uganda.

PMID- 29186450
TI  - SPECTRE: a suite of phylogenetic tools for reticulate evolution.
AB  - Summary: Split-networks are a generalization of phylogenetic trees that have
      proven to be a powerful tool in phylogenetics. Various ways have been developed
      for computing such networks, including split-decomposition, NeighborNet, QNet and
      FlatNJ. Some of these approaches are implemented in the user-friendly SplitsTree
      software package. However, to give the user the option to adjust and extend these
      approaches and to facilitate their integration into analysis pipelines, there is
      a need for robust, open-source implementations of associated data structures and
      algorithms. Here, we present SPECTRE, a readily available, open-source library of
      data structures written in Java, that comes complete with new implementations of
      several pre-published algorithms and a basic interactive graphical interface for
      visualizing planar split networks. SPECTRE also supports the use of longer
      running algorithms by providing command line interfaces, which can be executed on
      servers or in High Performance Computing environments. Availability and
      implementation: Full source code is available under the GPLv3 license at:
      https://github.com/maplesond/SPECTRE. SPECTRE's core library is available from
      Maven Central at: https://mvnrepository.com/artifact/uk.ac.uea.cmp.spectre/core.
      Documentation is available at: http://spectre-suite-of-phylogenetic-tools-for
      reticulate-evolution.readthedocs.io/en/latest/. Contact:
      sarah.bastkowski@earlham.ac.uk. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29186449
TI  - The Thyroid Hormone Inactivating Type 3 Deiodinase Is Essential for Optimal
      Neutrophil Function: Observations From Three Species.
AB  - Neutrophils are essential effector cells of the innate immune system that have
      recently been recognized as thyroid hormone (TH) target cells. Cellular TH
      bioavailability is regulated by the deiodinase enzymes, which can activate or
      inactivate TH. We have previously shown that the TH inactivating enzyme type 3
      deiodinase (D3) is present in neutrophils. Furthermore, D3 knockout (D3KO) mice
      show impaired bacterial killing upon infection. We hypothesized that D3 plays a
      role in neutrophil function during infection by actively regulating local TH
      availability. We measured TH concentrations in cerebrospinal fluid (CSF) from
      patients with bacterial meningitis and controls. Bacterial meningitis resulted in
      marked changes in CSF TH levels, characterized by a strong increase of thyroxine
      and reverse-triiodothyronine concentrations. This altered TH profile was
      consistent with elevated D3 activity in infiltrating neutrophils at the site of
      infection. D3 knockdown in zebrafish embryos with pneumococcal meningitis
      resulted in increased mortality and reduced neutrophil infiltration during
      infection. Finally, stimulated neutrophils from female D3KO mice exhibited
      impaired NADPH-oxidase activity, an important component of the neutrophil
      bacterial killing machinery. These consistent findings across experimental models
      strongly support a critical role for reduced intracellular TH concentrations in
      neutrophil function during infection, for which the TH inactivating enzyme D3
      appears essential.

PMID- 29186451
TI  - Calcium Alginate-Caged Multiwalled Carbon Nanotubes Dispersive Microsolid Phase
      Extraction Combined With Gas Chromatography-Flame Ionization Detection for the
      Determination of Polycyclic Aromatic Hydrocarbons in Water Samples.
AB  - In this study, caged calcium alginate-caged multiwalled carbon nanotubes
      dispersive microsolid phase extraction was described for the first time for the
      extraction of polycyclic aromatic hydrocarbons (PAHs) from water samples prior to
      gas chromatographic analysis. Fluorene, phenanthrene and fluoranthene were
      selected as model compounds. The caged calcium alginate-caged multiwalled carbon
      nanotubes was characterized by Fourier transform infrared spectroscopy, scanning
      electron microscopy and thermal gravimetry analyses. The effective parameters
      namely desorption solvent, solvent volume, extraction time, desorption time, the
      mass of adsorbent and sample volume were optimized. Under the optimum extraction
      conditions, the developed method showed good linearity in the range of 0.5-50 ng
      mL-1 (R2 >= 0.996), low limits of detection and quantification (0.42-0.22 ng mL
      1) (0.73-1.38 ng mL-1) respectively, good relative recoveries (71.2-104.2%) and
      reproducibility (RSD 1.8-12.4%, n = 3) for the studied PAHs in water sample. With
      high enrichment factor (1,000), short extraction time (<30 min), low amounts of
      adsorbent (100 mg) and low amounts of solvent (0.1 mol) have proven that the
      microsolid phase extraction method based on calcium alginate-caged multiwalled
      carbon nanotubes are environmentally friendly and convenient extraction method to
      use as an alternative adsorbent in the simultaneous preconcentration of PAHs from
      environmental water samples.

PMID- 29186452
TI  - Gender and cardiovascular disease: are sex-biased microRNA networks a driving
      force behind heart failure with preserved ejection fraction in women?
AB  - Cardiovascular disease (CVD) is the primary cause of death among men and women
      worldwide. Nevertheless, our comprehension of how CVD progresses in women and
      elicits clinical outcomes is lacking, leading CVD to be under-diagnosed and under
      treated in women. A clear example of this differential presentation of CVD
      pathophysiologies in females is the strikingly higher prevalence of heart failure
      with preserved ejection fraction (HFpEF). Women with a history of pre-eclampsia
      or those who present with co-morbidities such as obesity, hypertension, and
      diabetes mellitus are at increased risk of developing HFpEF. Long understood to
      be a critical CVD risk factor, our understanding of how gender differentially
      affects the development of CVD has been greatly expanded by extensive genomic and
      transcriptomic studies. These studies uncovered a pivotal role for differential
      microRNA (miRNA) expression in response to systemic inflammation, where their co
      ordinated expression forms a post-transcriptional regulatory network that
      instigates microcirculation defects. Importantly, the potential sex-biased
      expression of the given miRNAs may explain sex-specific cardiovascular
      pathophysiologies in women, such as HFpEF. Sex-biased miRNAs are regulated by
      oestrogen (E2) in their transcription and processing or are expressed from loci
      on the X-chromosome due to incomplete X-chromosome inactivation. Interestingly,
      while E2-induced miRNAs predominantly appear to serve protective functions, it
      could be argued that many X-linked miRNAs have been found to challenge
      microvascular and myocardial integrity. Therefore, menopausal E2 deficiency,
      resulting in protective miRNA loss, and the augmentation of X-linked miRNA
      expression, may well contribute to the molecular mechanisms that underlie the
      female-specific cardiovascular aetiology in HFpEF.

PMID- 29186453
TI  - Detection and quantification of codeine-6-glucuronide, hydromorphone-3
      glucuronide, oxymorphone-3-glucuronide, morphine 3-glucuronide and morphine-6
      glucuronide in human hair from opioid users by LC-MS-MS.
AB  - Current hair testing methods that rely solely on quantification of parent drug
      compounds are unable to definitively distinguish between drug use and external
      contamination. One possible solution to this problem is to confirm the presence
      of unique drug metabolites that cannot be present through contamination, such as
      phase II glucuronide conjugates. This work demonstrates for the first time that
      codeine-6-glucuronide, hydromorphone-3-glucuronide, oxymorphone-3-glucuronide,
      morphine-3-glucuronide and morphine-6-glucuronide are present at sufficient
      concentrations to be quantifiable in hair of opioid users and that their
      concentrations generally increase as the concentrations of the corresponding
      parent compounds increase. Here, we present a validated liquid chromatography
      tandem mass spectrometry method to quantify codeine-6-glucuronide, dihydrocodeine
      6-glucuronide, hydromorphone-3-glucuronide, morphine-3-glucuronide, morphine-6
      glucuronide, oxymorphone-3-glucuronide, codeine, dihydrocodeine, dihydromorphine,
      hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone and 6-acetylmorphine
      in human hair. The method was used to analyze 46 human hair samples from known
      drug users that were confirmed positive for opioids by an independent laboratory.
      Glucuronide concentrations in samples positive for parent analytes ranged from ~1
      to 25 pg/mg, and most samples had glucuronide concentrations in the range of ~1
      to 5 pg/mg. Relative to the parent concentrations, the average concentrations of
      the four detected glucuronides were as follows: codeine-6-glucuronide, 2.33%;
      hydromorphone-3-glucuronide, 0.94%; oxymorphone-3-glucuronide, 0.77%; morphine 3
      glucuronide, 0.59%; and morphine-6-glucuronide, 0.93%.

PMID- 29186454
TI  - External applicability of the COMPASS trial: an analysis of the reduction of
      atherothrombosis for continued health (REACH) registry.
AB  - Aims: The aims of the present study were to describe the proportion of patients
      eligible for the COMPASS trial within the Reduction of Atherothrombosis for
      Continued Health (REACH) registry, the reasons for ineligibility, and to put in
      perspective the characteristics and outcomes of trial-eligible patients from the
      REACH registry compared with those of patients enrolled in the reference aspirin
      arm of the COMPASS trial. Methods and results: The COMPASS selection and
      exclusion criteria were applied to REACH patients with either coronary artery
      disease (CAD) or peripheral artery disease (PAD). We used the COMPASS primary
      composite outcome of cardiovascular (CV) death, myocardial infarction (MI), or
      stroke. In REACH, 31 873 patients had CAD or PAD and detailed information
      allowing evaluation of eligibility. Among these, 9518 (29.9%) patients had
      exclusion criteria and an additional 5480 patients (17.2%) did not fulfil the
      inclusion criteria and thus were not eligible. The 'COMPASS-Eligible' population
      therefore comprised 52.9% of the evaluable REACH patients (n = 16 875). The main
      reasons for exclusion were high-bleeding risk (51.8%), anticoagulant use (44.8%),
      requirement for dual antiplatelet therapy within 1 year of an ACS or PCI with
      stent, (25.9%), history of ischaemic stroke <1 year (12.4%), and severe renal
      failure (2.2%). Eligibility was highest among patients with PAD alone (68.4%).
      COMPASS-Eligible patients from REACH experienced higher annualized primary
      outcome event rates than patients actually enrolled in the reference aspirin arm
      of COMPASS (4.2% vs. 2.9% per year, P < 0.001). Conclusion: COMPASS-Eligible
      patients represent a substantial fraction of stable CAD/PAD patients encountered
      in routine clinical practice in the large international REACH registry suggesting
      good external applicability. COMPASS-Eligible patients experienced a higher rate
      of the primary outcome compared with COMPASS participants in the aspirin alone
      treatment arm.

PMID- 29186455
TI  - Recommendations for Toxicological Investigation of Drug-Impaired Driving and
      Motor Vehicle Fatalities-2017 Update.
AB  - This report describes the outcomes of a process undertaken to review and update
      the National Safety Council's Alcohol, Drugs and Impairment Division's
      recommendations for the toxicological investigation of suspected alcohol and drug
      impaired driving cases and motor vehicle fatalities. The updates to the
      recommendations are made based on a survey of practices in laboratories in the
      USA and Canada performing testing in these cases, consideration of existing
      epidemiological crash and arrest data, current drug use patterns, and practical
      considerations of widely available technology platforms in laboratories
      performing this work. The final recommendations updates are derived from a
      consensus meeting of experts recruited from survey respondents and the membership
      of the National Safety Council's Alcohol, Drug and Impairment Division. The
      principal changes in this round of recommendations include removal of butalbital,
      phenobarbital, and phencyclidine from Tier I (mandatory) to Tier II (optional)
      due to changes in prevalence. In addition, buprenorphine, fentanyl, tramadol, and
      their metabolites were moved from Tier II to Tier I due to increased prevalence
      and concerns about their potential for causing impairment. In addition, screening
      and confirmatory cutoffs for the oral fluid scope were further refined. Other
      additions were made to the list of Tier II compounds including fentanyl analogs
      (e.g., acetylfentanyl, butyrylfentanyl, furanylfentanyl, etc), mitragynine, novel
      opioids (e.g., MT-45, U-47700), atypical antipsychotics, and novel
      benzodiazepines (e.g., clonazolam, flubromazolam, etc).

PMID- 29186456
TI  - The Anti-Human Immunodeficiency Virus Drug Tenofovir, a Reverse Transcriptase
      Inhibitor, Also Targets the Herpes Simplex Virus DNA Polymerase.
AB  - Background: Genital herpes is an important cofactor for acquisition of human
      immunodeficiency virus (HIV) infection, and effective prophylaxis is a helpful
      strategy to halt both HIV and herpes simplex virus (HSV) transmission. The
      antiretroviral agent tenofovir, formulated as a vaginal microbicide gel, was
      shown to reduce the risk of HIV and HSV type 2 (HSV-2) acquisition. Methods: HSV
      type 1 (HSV-1) and HSV-2 mutants were selected for resistance to tenofovir and
      PMEO-DAPy (6-phosphonylmethoxyethoxy-2,4-diaminopyrimidine, an acyclic nucleoside
      phosphonate with dual anti-HSV and anti-HIV activity) by stepwise dose
      escalation. Several plaque-purified viruses were characterized phenotypically
      (drug resistance profiling) and genotypically (sequencing of the viral DNA
      polymerase gene). Results: Tenofovir resistant and PMEO-DAPy-resistant viruses
      harbored specific amino acid substitutions associated with resistance not only to
      tenofovir and PMEO-DAPy but also to acyclovir and foscarnet. These amino acid
      changes (A719V, S724N, and L802F [HSV-1] and M789T and A724V [HSV-2]) were also
      found in clinical isolates recovered from patients refractory to acyclovir and/or
      foscarnet therapy or in laboratory-derived strains. A total of 10 (HSV-1) and 18
      (HSV-2) well-characterized DNA polymerase mutants had decreased susceptibility to
      tenofovir and PMEO-DAPy. Conclusions: Tenofovir and PMEO-DAPy target the HSV DNA
      polymerase, and clinical isolates with DNA polymerase mutations emerging under
      acyclovir and/or foscarnet therapy showed cross-resistance to tenofovir and PMEO
      DAPy.

PMID- 29186457
TI  - Reproductive Hormone Levels Predict Changes in Frailty Status in Community
      Dwelling Older Men: European Male Ageing Study Prospective Data.
AB  - Context: Clinical sequelae of androgen deficiency share common features with
      frailty. Evidence supporting the role of androgens in the development of frailty
      is limited and conflicting. Objective: To determine associations between male
      reproductive hormones and prospective changes in frailty status. Design/Setting:
      A 4.3-year prospective cohort study of community-dwelling men participating in
      the European Male Ageing Study. Participants: A total of 3369 men aged 40 to 79
      from eight European centers. Intervention: None. Main Outcome Measure: Frailty
      status was determined using frailty index (FI; n = 2278) and frailty phenotype
      (FP; n = 1980). Results: After adjusting for baseline frailty, age, center, and
      smoking, the risk of worsening FI decreased with higher testosterone (T), free T,
      and dihydrotestosterone (DHT) [percentage change (95% confidence interval) in FI
      associated with 1 standard deviation higher hormone level: -3.0 (-5.9, -1.0) for
      total T; -3.9 (-6.8, -2.0) for free T; and -3.9 (-6.8, -2.0) for DHT]. After
      further adjustment for body mass index, only free T remained a significant
      predictor of FI change. In fully adjusted models, higher luteinizing hormone and
      follicle-stimulating hormone were positively related to worsening FI only in men
      <60 years, and higher estradiol predicted lower likelihood of improving FP [odds
      ratio: 0.68 (0.52, 0.88)]. Conclusions: These prospective data support the
      hypothesis that higher androgen levels may protect elderly men from worsening
      frailty. However, the causal nature of these relationships requires further
      investigation. Whereas raised gonadotropins in men <60 years might be an early
      marker of frailty, the role of estradiol in frailty needs further clarification.

PMID- 29186458
TI  - Four-days-a-week antiretroviral maintenance therapy in virologically controlled
      HIV-1-infected adults: the ANRS 162-4D trial.
AB  - Background: Intermittent treatment could improve the convenience, tolerability
      and cost of ART, as well as patients' quality of life. We conducted a 48 week
      multicentre study of a 4-days-a-week antiretroviral regimen in adults with
      controlled HIV-1-RNA plasma viral load (VL). Methods: Eligible patients were
      adults with VL < 50 copies/mL for at least 1 year on triple therapy with a
      ritonavir-boosted PI (PI/r) or an NNRTI. The study protocol consisted of the same
      regimen taken on four consecutive days per week followed by a 3 day drug
      interruption. The primary outcome was the proportion of participants remaining in
      the strategy with VL < 50 copies/mL up to week 48. The study was designed to show
      an observed success rate of > 90%, with a power of 87% and a 5% type 1 error. The
      study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014
      000146-29). Results: One hundred patients (82 men), median age 47 years (IQR 40
      53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3)
      years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing
      regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of
      participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week
      regimen. Virological failure occurred in three participants, who all resumed
      daily treatment and became resuppressed. One participant stopped the strategy. No
      severe treatment-related events occurred. Conclusions: Antiretroviral maintenance
      therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to
      potential reduction of long-term toxicities, high adherence to the antiretroviral
      regimen and drug cost saving.

PMID- 29186459
TI  - The long-term impact of a change in Effort-Reward imbalance on mental health
      results from the prospective MAN-GO study.
AB  - Background: Little is yet known on the long-term effects of stress management
      interventions (SMIs) in the workplace. The aim this study was to prospectively
      examine the effect of an improvement of psychosocial working conditions measured
      by the Effort-Reward (E-R) Imbalance model within 2 years following an SMI, and
      mental health 7 years later. Methods: The study sample consisted of 97 male
      industrial workers from southern Germany. Data were collected pre- and post
      intervention in 2006 (T1) and 2008 (T2), respectively, as well as in 2015 (T3).
      Change scores were computed by subtracting T1 from T3 values. The associations
      between E-R ratio at T1, T2 and the change score, respectively, with depression
      and anxiety 7 years later were estimated by means of linear regression analysis.
      Analyses were adjusted for baseline levels of the exposure and outcome variables,
      socio-demographic-, health- and work-related covariates. Results: Within-person
      comparisons revealed a significant reduction (i.e. improvement) in E-R ratio post
      intervention (-0.103, SD 0.24, P = 0.000). This improvement in the E-R ratio was
      significantly associated with lower anxiety (beta = 0.358, P = 0.001) and
      depression (beta = 0.246, P = 0.031) scores in the fully adjusted models. The
      association between change scores and mental health were slightly stronger than
      associations with absolute values at T1 and T2. Conclusions: An improvement in E
      R ratio following an SMI, was significantly associated with lower anxiety and
      depression 7 years later. These results strongly support the importance of
      improving psychosocial working conditions in order to protect the mental health
      of employees in the long-run.

PMID- 29186461
TI  - Advancing the evaluation of cervical cancer screening: development and
      application of a longitudinal adherence metric.
AB  - Background: Attendance to routine cancer screening at repeated intervals is
      essential for reducing morbidity and mortality of targeted cancers, yet currently
      defined quality-assurance metrics evaluate coverage within a defined period of
      time (e.g. 3.5 years). Methods: We developed a longitudinal adherence metric that
      captures attendance to cancer screening at repeated intervals, and applied the
      metric to population-based data from the Cancer Registry of Norway that captures
      two decades of organised cervical cancer screening, including all screening tests
      and cervical cancer diagnoses for women living in Norway at any time during years
      1992-2013 and eligible for at least two screening rounds (1 round = 3.5 years, N
      = 1 391 812). For each woman, we calculated the proportion of eligible screening
      rounds with at least one registered cytology test, and categorised women into one
      of five longitudinal adherence categories: never-screeners, severe under
      screeners, moderate under-screeners, guidelines-based screeners and over
      screeners. For each category, we evaluated cancer outcomes such as cancer stage
      at diagnosis. Results: Only 46% of screen-eligible women were consistently
      screened at least once every 3.5 years, and the majority of these were over
      screened. In contrast, 29% were moderately under-screened, 17% were severely
      under-screened and 8% had never attended screening. Screening behaviour was
      associated with cancer outcomes; e.g., the proportion of cancers diagnosed at
      Stage I increased from 21% among never-screeners to 70% among over-screeners.
      Conclusion: The longitudinal adherence metric evaluates screening performance as
      a succession of screening episodes, reflecting both guidelines and the
      fundamental principles of screening, and may be a valuable addition to existing
      performance indicators.

PMID- 29186460
TI  - Understanding the relation between socioeconomic position and inflammation in
      post-menopausal women: education, income and occupational prestige.
AB  - Background: The role of occupational prestige, a direct measure of the perceived
      status of job and job holder, in inflammation is unknown. To contribute to
      understanding the pathways by which socioeconomic position (SEP) is associated
      with inflammation, we aimed to estimate the direct effects of education, income
      and occupational prestige on C-reactive protein (CRP) and to describe the
      relationship between these markers and CRP. Methods: The study was based on 2026
      post-menopausal women enrolled in the Women's Health Initiative-Observational
      Study. Occupational prestige was determined by linking a text description of
      longest held occupation with a social status item from the Occupational
      Information Network. Path analysis was employed to estimate direct and mediated
      effects. Results: The study suggests that higher levels of education, income, and
      occupational prestige are associated with 8% (95% CI as percentage change -12, 
      4), 5% [95% CI (-8, -2) and 4% (95% CI - 7, -1)] lower levels of CRP,
      respectively. The inverse association between education and CRP was explained by
      the effect of education on income and occupational prestige. The effect of
      occupational prestige on CRP was independent of mediators in the model.
      Conclusions: The findings indicate that education may work to influence CRP
      primarily through increasing income and occupational prestige and provides
      evidence that occupational prestige captures a unique aspect of SEP.

PMID- 29186462
TI  - Haemorrhagic fever with renal syndrome in Montenegro, 2004-14.
AB  - From 2004 to 2014, 106 cases of Human haemorrhagic fever with renal syndrome were
      notified in Montenegro, with a peak in 2014. Most of the cases occurred in
      summer, in the North-east and Central Montenegro, a hilly/mountainous area, that
      provides suitable habitats for the main rodent carriers. Cases were mainly males
      (71) and exposures were often working outdoor or spending time visiting mountains
      and lakes. Incidence correlated with average annual temperature increase and
      average annual rainfalls decrease, but not with land cover. Environment and
      climate effects on HFRS in Montenegro need further investigation to get insight
      into future trends.

PMID- 29186463
TI  - Does public reporting influence quality, patient and provider's perspective,
      market share and disparities? A review.
AB  - Background: Public reporting (PR) of healthcare (HC) provider's quality was
      proposed as a public health instrument for providing transparency and
      accountability in HC. Our aim was to assess the impact of PR on five main
      domains: quality improvement; patient choice, service utilization and market
      share; provider's perspective; patient experience; and unintended consequences.
      Methods: PubMed, Scopus, ISI WOS, and EconLit databases were searched to identify
      studies investigating relationships between PR and five main domains, published
      up to April 1, 2016. Results: Sixty-two papers published between 1988 and 2015
      were included. Nineteen studies investigated quality improvement, 19 studies
      explored the unintended consequences of PR, 10 explored the effects on market
      share, 10 on patients' choice, 7 evaluated the provider's perspective, 4 economic
      outcome, 4 service utilization, 2 purchasers' use of PR and 2 studies explored
      patient experiences. The effect of PR was diverse throughout the studies-mostly
      positive on: patient experience (100%), quality improvement (63%), patient
      choice, service utilization and market share (46%); mixed on provider's
      perspective and economic outcome (27%) and mainly negative on unintended
      consequences (68%). Conclusions: Our research covering different outcomes and
      settings reported that PR is associated with changes in HC provider's behavior
      and can influence market share. Unintended consequences are a concern of PR and
      should be taken into account when allocating HC resources. The experiences
      collected in this paper could give a snapshot about the impact of PR on a HC
      user's perception of the providers' quality of care, helping them to make
      empowered choices.

PMID- 29186464
TI  - Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case
      control study.
AB  - Background: Although recent studies have indicated the potential adverse effects
      of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk
      of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the
      relationship between maternal BPA exposure and the risk of pre-eclampsia.
      Methods: We conducted a nested case-control study among 173 women (74 cases of
      pre-eclampsia and 99 controls). BPA concentrations were measured using liquid
      chromatography-mass spectrometry in the maternal serum samples collected during
      16-20 gestational weeks. Multivariate logistic models were used to examine the
      relationship between maternal serum BPA concentrations and the risk of pre
      eclampsia. Results: BPA was detectable (>0.1 ug/l) in 78.6% of the maternal serum
      samples at three levels: low (<2.24 ug/l), medium (2.24-4.44 ug/l), and high
      (>4.44 ug/l). BPA concentrations were significantly higher in the serum samples
      collected from the pre-eclampsia cases than those from controls (median: 3.40 vs.
      1.50 ug/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the
      odds of developing pre-eclampsia were significantly elevated in subjects with
      high serum BPA levels compared with those with low levels (adjusted OR = 16.46,
      95%CI = 5.42-49.85) regardless of subcategories of pre-eclampsia including
      severity and onset time. Among the pre-eclampsia subjects, the maternal serum
      concentration of BPA was not different between the early- and late-onset subjects
      (median: 3.09 vs. 3.50 ug/l, P = 0.57), but surprisingly higher in mild pre
      eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs.
      1.80 ug/l, P < 0.01). Conclusions: These results demonstrated that maternal
      exposure to high level of BPA could be associated with an increased risk of pre
      eclampsia.

PMID- 29186466
TI  - Suppression of Mediterranean Fruit Fly (Diptera: Tephritidae) With Trimedlure and
      Biolure Dispensers in Coffea arabica (Gentianales: Rubiaceae) in Hawaii.
AB  - To assess the potential to suppress Mediterranean fruit fly, Ceratitis capitata
      (Wiedemann; Diptera: Tephritidae), via mass trapping with Trimedlure (TML), we
      compared fly catch (as catch per trap per time period) provided by either a
      novel, solid, triple-lure dispenser with TML, methyl eugenol (ME), and raspberry
      ketone (RK) (TMR) or solid TML plugs, both without insecticides, in addition to
      Biolure bait stations. Work was done in a coffee plantation that had a dense C.
      capitata population. Three treatments were compared: 1) TMR or TML (50 traps per
      ha), 2) Biolure (50 traps per ha), 3) TML (25 per ha) or TMR (25 per ha) +
      Biolure (25 per ha), and 4) an untreated control. During coffee season, based on
      C. capitata captures (mean flies per trap per wk) inside plastic McPhail traps,
      all treatments were significantly different than the control: Biolure (9.57) =
      TMR (11.28) = Biolure +TMR (13.50) < Control (36.06 flies/trap/wk). During non
      coffee season, all treatments were significantly different than the control and
      TML was significantly lower than Biolure (wax matrix bait stations): TML (0.95) <
      Biolure (1.43) = Biolure +TML (1.77) < Control (2.81 flies/trap/wk).
      Surprisingly, captures were not lower in plots treated with combinations of
      Biolure + TMR or TML, compared to individual plots with Biolure or TML or TMR
      alone. Mass trapping with either TML or TMR dispensers deserves further study as
      a component of Integrated Pest Management programs for C. capitata in Hawaii and
      may have global potential for management of C. capitata.

PMID- 29186467
TI  - Biological functions of sulfoglycolipids and the EMARS method for identification
      of co-clustered molecules in the membrane microdomains.
AB  - Two major sulfoglycolipids, sulfatide (SO3-3Gal-ceramide) and seminolipid (SO3
      3Gal-alkylacylglycerol) exist in mammals. Sulfatide is abundant in the myelin
      sheath and seminolipid is unique to the spermatogenic cells. The carbohydrate
      moiety of sulfatide and seminolipid is identical and synthesized by common
      enzymes: ceramide galactosyltransferase (CGT) and cerebroside sulfotransferase
      (CST). We have purified CST homogenously, cloned the CST gene and generated CST
      knockout mice. CST-null mice completely lack sulfoglycolipids all over the body.
      Analysis of CST-null mice has revealed that sulfatide is an essential component
      for the axo-glial junction at the paranode region and regulates terminal
      differentiation of oligodendrocytes, and that seminolipid is responsible for the
      formation of a functional lactate transporter assembly to take up the critical
      energy source for spermatocytes. We have developed a new analytical method termed
      EMARS to identify co-clustered molecules in the membrane microdomains in order to
      elucidate the functional molecules that collaborate with sulfoglycolipids.

PMID- 29186468
TI  - Analysis of Memory B-Cell Responses Reveals Suboptimal Dosing Schedule of a
      Licensed Vaccine.
AB  - Current guidance recommends that adolescents receive a 2-dose human
      papillomavirus (HPV) vaccine, whereas young adults and immunocompromised persons
      receive 3 doses. We examined secondary responses of vaccine-elicited memory B
      cells (Bmem) in naive women receiving 3 doses of the quadrivalent HPV vaccine to
      understand the quality of B-cell memory generated by this highly effective
      vaccine. Unexpectedly, we observed a lower Bmem response rate and magnitude of
      Bmem responses to the third dose than to a booster dose administered at month 24.
      Moreover, high titers of antigen-specific serum antibody at vaccination inversely
      correlated with Bmem responses. As the purpose of additional doses/boosters is to
      stimulate Bmem to rapidly boost antibody levels, these results indicate the
      timing of the third dose is suboptimal and lend support to a 2-dose HPV vaccine
      for young adults. Our findings also indicate more broadly that multidose vaccine
      schedules should be rationally determined on the basis of Bmem responses.

PMID- 29186469
TI  - GDP-L-fucose is required for boundary definition in plants.
AB  - The CUP-SHAPED COTYLEDON (CUC) transcription factors control plant boundary
      formation, thus allowing the emergence of novel growth axes. While the
      developmental roles of the CUC genes in different organs and across species are
      well characterized, upstream and downstream events that contribute to their
      function are still poorly understood. To identify new players in this network, we
      performed a suppressor screen of CUC2g-m4, a line overexpressing CUC2 that has
      highly serrated leaves. We identified a mutation that simplifies leaf shape and
      affects MURUS1 (MUR1), which is responsible for GDP-L-fucose production. Using
      detailed morphometric analysis, we show that GDP-L-fucose has an essential role
      in leaf shape acquisition by sustaining differential growth at the leaf margins.
      Accordingly, reduced CUC2 expression levels are observed in mur1 leaves.
      Furthermore, genetic analyses reveal a conserved role for GDP-L-fucose in
      different developmental contexts where it contributes to organ separation in the
      same pathway as CUC2. Taken together, our results reveal that GDP-L-fucose is
      necessary for proper establishment of boundary domains in various developmental
      contexts.

PMID- 29186470
TI  - Determination of Acetaminophen, Dexchlorpheniramine, Caffeine, Cotinine and
      Salicylic acid in 100 MUL of Whole Blood by UHPLC-MS/MS.
AB  - A sensitive and robust ultra-high-performance liquid chromatography-tandem mass
      spectrometry method has been developed and validated for the quantification of
      acetaminophen, dexchlorpheniramine, caffeine, cotinine and salicylic acid in
      postmortem blood samples from children younger than 4 years. The sample was
      prepared by a protein precipitation with ice-cold methanol/acetonitrile mixture
      (85:15, v/v). The organic phase was evaporated to dryness and the residue was
      dissolved in the mobile phase. Separation, with gradient elution and an acidic
      mobile phase, was achieved on an Acquity UPLC(r) HSS T3 column. The compounds
      were quantified using a multiple reaction-monitoring mode. Two transitions were
      monitored for each compound and one for the deuterated internal standards. The
      mass spectrometric detection in the positive ion mode was performed for all the
      compounds except salicylic acid which was detected in the negative ionization
      mode. The limits of quantification were as follows: acetaminophen 0.30 mg/L,
      dexchlorpheniramine 0.0050 mg/L, caffeine 0.099 mg/L, cotinine 0.00035 mg/L and
      salicylic acid 1.3 mg/L. Between-assay and within-assay precisions were <=15%
      (biases: -10% to 26%) and <=10%, respectively. Extraction recoveries varied from
      93% to 137%. The matrix effects in blood, corrected with deuterated internal
      standards, were 100% +/- 10% for all compounds except dexchlorpheniramine (111%)
      and caffeine (138%).

PMID- 29186471
TI  - Reduced proximal tubular expression of protein endocytic receptors in proteinuria
      is associated with urinary receptor shedding.
AB  - Background: Filtered proteins, including albumin, are reabsorbed in the proximal
      tubule (PT) mediated by megalin, cubilin and the neonatal Fc receptor (FcRn).
      Proteinuria is an important renal biomarker linked to poor prognosis but
      expression of these key receptors is not well studied. Methods: Megalin
      expression was determined at protein and messenger RNA (mRNA) levels in kidneys
      from proteinuric patients, and the expression of megalin, cubilin and FcRn was
      examined in the kidneys of mice with protein-overload proteinuria. The presence
      of receptors in the urine of proteinuric and control mice was also studied.
      Results: In nephrotic patients, megalin expression is reduced while mRNA is
      increased. In proteinuric mice megalin, cubilin and the neonatal FcRn protein are
      all reduced in PTs. Megalin and FcRn mRNA are increased in proteinuric mice,
      whereas that for cubilin was reduced. In proteinuric mice increased urinary
      excretion of each of these endocytic receptors was observed. Conclusions: It is
      concluded that in proteinuria, expression of all the key protein re-absorptive
      receptors is significantly reduced in the PT in association with increased
      turnover and urinary shedding.

PMID- 29186472
TI  - Combination Therapy With Neuraminidase and Polymerase Inhibitors in Nude Mice
      Infected With Influenza Virus.
AB  - Background: Treatment of immunocompromised, influenza virus-infected patients
      with the viral neuraminidase inhibitor oseltamivir often leads to the emergence
      of drug-resistant variants. Combination therapy with compounds that target
      different steps in the viral life cycle may improve treatment outcomes and reduce
      the emergence of drug-resistant variants. Methods: Here, we infected
      immunocompromised nude mice with an influenza A virus and treated them with
      neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir)
      inhibitors, or combinations thereof. Results: Combination therapy for 28 days
      increased survival times compared with monotherapy, but the animals died after
      treatment was terminated. Mono- and combination therapies did not consistently
      reduce lung virus titers. Prolonged viral replication led to the emergence of
      neuraminidase inhibitor-resistant variants, although viruses remained sensitive
      to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase
      inhibitors. Conclusions: Collectively, our data demonstrate that combination
      therapy in immunocompromised hosts increases survival times, but does not
      suppress the emergence of neuraminidase inhibitor-resistant variants.

PMID- 29186474
TI  - Whole Mitochondrial Genomic and Y-Chromosomal Phylogenies of Burmese Long-Tailed
      Macaque (Macaca fascicularis aurea) Suggest Ancient Hybridization between
      fascicularis and sinica Species Groups.
AB  - Macaca fascicularis aurea (Burmese long-tailed macaque) is 1 of the 10 subspecies
      of Macaca fascicularis. Despite having few morphological differences from other
      subspecies, a recent phylogeographic study showed that M. f. aurea is clearly
      distinct genetically from Macaca fascicularis fascicularis (common long-tailed
      macaque) and suggests that M. f. aurea experienced a disparate evolutionary
      pathway versus other subspecies. To construct a detailed evolutionary history of
      M. f. aurea and its relationships with other macaque species, we performed
      phylogenetic analyses and divergence time estimation of whole mitochondrial
      genomes (2 M. f. aurea, 8 M. f. fascicularis, and 16 animals of 12 macaque
      species) and 2871 bp of the Y chromosome (1 M. f. aurea, 2 M. f. fascicularis,
      and 5 animals of 5 macaque species) and haplotype network analysis of 758 bp of
      the Y chromosome (1 M. f. aurea, 2 M. f. fascicularis, and 21 animals of 19
      macaque species). Whereas the Y chromosome of M. f. aurea clustered with those of
      the fascicularis species group in the phylogenetic and haplotype network
      analyses, its mtDNA clustered within the clade of the sinica species group. Based
      on this phylogenetic incongruence and the estimated divergence times, we propose
      that proto-M. f. aurea underwent hybridization with a population of the sinica
      species group between 2.5 and 0.95 MYA after divergence from the common ancestor
      of M. fascicularis. Hybridization and introgression might have been central in
      the evolution of M. f. aurea, similar to what occurred in the evolution of other
      macaque species and subspecies.

PMID- 29186473
TI  - Meta-analysis of thirty-two case-control and two ecological radon studies of lung
      cancer.
AB  - A re-analysis has been carried out of thirty-two case-control and two ecological
      studies concerning the influence of radon, a radioactive gas, on the risk of lung
      cancer. Three mathematically simplest dose-response relationships (models) were
      tested: constant (zero health effect), linear, and parabolic (linear-quadratic).
      Health effect end-points reported in the analysed studies are odds ratios or
      relative risk ratios, related either to morbidity or mortality. In our
      preliminary analysis, we show that the results of dose-response fitting are
      qualitatively (within uncertainties, given as error bars) the same, whichever of
      these health effect end-points are applied. Therefore, we deemed it reasonable to
      aggregate all response data into the so-called Relative Health Factor and jointly
      analysed such mixed data, to obtain better statistical power. In the second part
      of our analysis, robust Bayesian and classical methods of analysis were applied
      to this combined dataset. In this part of our analysis, we selected different
      subranges of radon concentrations. In view of substantial differences between the
      methodology used by the authors of case-control and ecological studies, the
      mathematical relationships (models) were applied mainly to the thirty-two case
      control studies. The degree to which the two ecological studies, analysed
      separately, affect the overall results when combined with the thirty-two case
      control studies, has also been evaluated. In all, as a result of our meta
      analysis of the combined cohort, we conclude that the analysed data concerning
      radon concentrations below ~1000 Bq/m3 (~20 mSv/year of effective dose to the
      whole body) do not support the thesis that radon may be a cause of any
      statistically significant increase in lung cancer incidence.

PMID- 29186476
TI  - Reversible Notch1 acetylation tunes proliferative signalling in cardiomyocytes.
AB  - Aims: The Notch signalling pathway regulates the balance between proliferation
      and differentiation in several tissues, including the heart. Our previous work
      has demonstrated that the proliferative potential of neonatal cardiomyocytes
      relies on Notch1 activity. A deep investigation on the biochemical regulation of
      the Notch signalling in cardiomyocytes is the focus of the current research.
      Methods and results: We show that the Notch1 intracellular domain is acetylated
      in proliferating neonatal rat cardiomyocytes and that acetylation tightly
      controls the amplitude and duration of Notch signalling. We found that
      acetylation extends the half-life of the protein, and enhanced its
      transcriptional activity, therefore counteracting apoptosis and sustaining
      cardiomyocyte proliferation. Sirt1 acted as a negative modulator of Notch1
      signalling; its overexpression in cardiomyocytes reverted Notch acetylation and
      dampened its stability. A constitutively acetylated fusion protein between Notch1
      and the acetyltransferase domain of p300 promoted cardiomyocyte proliferation,
      which was remarkably sustained over time. Viral vector-mediated expression of
      this protein enhanced heart regeneration after apical resection in neonatal mice.
      Conclusion: These results identify the reversible acetylation of Notch1 as a
      novel mechanism to modulate its signalling in the heart and tune the
      proliferative potential of cardiomyocytes.

PMID- 29186475
TI  - ProphTools: general prioritization tools for heterogeneous biological networks.
AB  - Background: Networks have been proven effective representations for the analysis
      of biological data. As such, there exist multiple methods to extract knowledge
      from biological networks. However, these approaches usually limit their scope to
      a single biological entity type of interest or they lack the flexibility to
      analyze user-defined data. Results: We developed ProphTools, a flexible open
      source command-line tool that performs prioritization on a heterogeneous network.
      ProphTools prioritization combines a Flow Propagation algorithm similar to a
      Random Walk with Restarts and a weighted propagation method. A flexible model for
      the representation of a heterogeneous network allows the user to define a
      prioritization problem involving an arbitrary number of entity types and their
      interconnections. Furthermore, ProphTools provides functionality to perform cross
      validation tests, allowing users to select the best network configuration for a
      given problem. ProphTools core prioritization methodology has already been proven
      effective in gene-disease prioritization and drug repositioning. Here we make
      ProphTools available to the scientific community as flexible, open-source
      software and perform a new proof-of-concept case study on long noncoding RNAs
      (lncRNAs) to disease prioritization. Conclusions: ProphTools is robust
      prioritization software that provides the flexibility not present in other state
      of-the-art network analysis approaches, enabling researchers to perform
      prioritization tasks on any user-defined heterogeneous network. Furthermore, the
      application to lncRNA-disease prioritization shows that ProphTools can reach the
      performance levels of ad hoc prioritization tools without losing its generality.

PMID- 29186477
TI  - Host Specificity in Subarctic Aphids.
AB  - Plants and herbivorous (or parasitic) insects form the majority of macroscopic
      life. The specificity of interaction between host plant and parasitic insect
      depends on the adaptations of both the host and the parasite. Over time, these
      interactions evolve and change as a result of an 'arms race' between host and
      parasite, and the resulting species-specific adaptations may be maintained,
      perpetuating these interactions across speciation events. This can lead to
      specialisation between species or clades. With speciation and species sorting
      over time, complex interactions evolve. Here, we elucidate a three-tier method to
      test these interactions using the aphids (Hemiptera: Aphididae) and plants of
      Churchill (Manitoba, Canada) as a model system. We analyzed these interactions by
      testing for three patterns in host specificity: monophagy, phylogenetic
      clustering, and cophylogeny. We defined monophagy strictly as one species feeding
      exclusively upon a single host plant species (an association likely driven by
      arms races in morphology, chemical resistance/tolerance, and visual appearance)
      and observed this in 7 of 22 aphid species. In all the remaining 'polyphagous'
      cases, there was a strong trend toward monophagy (80% of individuals were found
      on a single host plant species). Second, we observed two separate examples of
      phylogenetic clustering where groups of closely related aphid species fed upon
      individual plant species. Finally, we found no support for cophylogenetic
      relationships where both aphids and plants cospeciate to form congruent
      phylogenetic trees (evidence of coadaptation through an ongoing arms race). One
      explanation for uncovering species-specific interactions in a recently
      deglaciated, subarctic locality is that the species involved in the associations
      moved north together. Testing different levels of specificity in the most
      predominant species-species interactions on the planet will allow us to elucidate
      these patterns accurately and gives us insight into where to direct future
      research.

PMID- 29186478
TI  - Randomized controlled trials in children's heart surgery in the 21st century: a
      systematic review.
AB  - OBJECTIVES: Randomized controlled trials are the gold standard for evaluating
      health care interventions, yet are uncommon in children's heart surgery. We
      conducted a systematic review of clinical trials in paediatric cardiac surgery to
      evaluate the scope and quality of the current international literature. METHODS:
      We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved
      references and systematic reviews to identify all randomized controlled trials
      reporting the effect of any intervention on the conduct or outcomes of heart
      surgery in children published in any language since January 2000; secondary
      publications and those reporting inseparable adult data were excluded. Two
      reviewers independently screened studies for eligibility and extracted data; the
      Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS: We
      identified 333 trials from 34 countries randomizing 23 902 children. Most were
      early phase (313, 94.0%), recruiting few patients (median 45, interquartile range
      28-82), and only 11 (3.3%) directly evaluated a surgical intervention. One
      hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a
      CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data
      Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69
      (20.7%) and unclear in 242 (72.7%). CONCLUSIONS: The recent literature in
      children's heart surgery contains few late-phase clinical trials. Most trials did
      not conform to the accepted standards of reporting, and the overall risk of bias
      was low in few studies. There is a need for high-quality, multicentre clinical
      trials to provide a robust evidence base for contemporary paediatric cardiac
      surgical practice.

PMID- 29186479
TI  - Febrile seizures prior to sudden cardiac death: a Danish nationwide study.
AB  - Aims: Febrile seizure (FS) is a common disorder affecting 2-5% of children up to
      5 years of age. The aim of this study was to determine whether FS in early
      childhood are over-represented in young adults dying from sudden cardiac death
      (SCD). Methods and results: We included all deaths (n = 4595) nationwide and
      through review of all death certificates, we identified 245 SCD in Danes aged 1
      30 years in 2000-09. Through the usage of nationwide registries, we identified
      all persons admitted with first FS among SCD cases (14/245; 5.7%) and in the
      corresponding living Danish population (71 027/2 369 785; 3.0%) and also in
      victims of transport accidents (26/917; 2.8%). The frequency of FS among SCD
      cases was significantly increased by an odds ratio of 1.96 [95% confidence
      interval (CI) 1.14-3.36; P = 0.021] compared with the living Danish population
      and with an odds ratio of 2.08 (95% CI 1.07-4.04; P = 0.046) compared with
      transport accident victims. SCD cases did not differ statistically in birth year
      (P = 0.272), age at SCD (P = 0.667) or prior medical conditions, except for
      epilepsy (P < 0.001), when comparing SCD with and without prior FS. The most
      common cause of death in autopsied SCD cases with FS was sudden arrhythmic death
      syndrome (5/8; 62.5%). Conclusion: In conclusion, this study demonstrates a
      significantly two-fold increase in the frequency of FS prior to death in young
      SCD cases compared with the two control groups, suggesting that FS could
      potentially contribute in a risk stratification model for SCD and warrant further
      studies.

PMID- 29186480
TI  - Gold nanoparticle printed coverslips to facilitate fluorescence-TEM correlative
      microscopy.
AB  - Correlative light and electron microscopy (CLEM) allows combining the advantages
      of fluorescence microscopy and electron microscopy for cell imaging. Rare
      phenomenon expressing cells can be studied by specifically tagged fluorophores
      with fluorescence microscopy. Subsequently, cells can be fixed and ultra
      structural details can be studied with transmission electron microscopy (TEM) at
      a higher resolution. However, precise landmarks are necessary to track the same
      cell throughout the CLEM process. In this technical report, we present a high
      contrast inkjet-printed gold nanoparticle patterns over commercial glass
      coverslip to facilitate cell tracking with correlative microscopy. High contrast
      and strong reflection from nano gold pattern can be used as a fixed landmark for
      cell identification with fluorescence microscopy. Nano gold printed letters over
      coverslips are visible in resin blocks, which can be further used to identify the
      cell of interest for performing sectioning of embedded cell blocks for TEM.

PMID- 29186481
TI  - Optimisation of trans-cinnamic acid and hydrocinnamyl alcohol production with
      recombinant Saccharomyces cerevisiae and identification of cinnamyl methyl ketone
      as a by-product.
AB  - Trans-cinnamic acid (tCA) and hydrocinnamyl alcohol (HcinOH) are valuable
      aromatic compounds with applications in the flavour, fragrance and cosmetic
      industry. They can be produced with recombinant yeasts from sugars via
      phenylalanine after expression of a phenylalanine ammonia lyase (PAL) and an aryl
      carboxylic acid reductase. Here, we show that in Saccharomyces cerevisiae a PAL
      enzyme from the bacterium Photorhabdus luminescens was superior to a previously
      used plant PAL enzyme for the production of tCA. Moreover, after expression of a
      UDP-glucose:cinnamate glucosyltransferase (FaGT2) from Fragaria x ananassa, tCA
      could be converted to cinnamoyl-D-glucose which is expected to be less toxic to
      the yeast cells. Production of tCA and HcinOH from glucose could be increased by
      eliminating feedback-regulated steps of aromatic amino acid biosynthesis and
      diminishing the decarboxylation step of the competing Ehrlich pathway. Finally,
      an unknown by-product resulting from further metabolisation of a carboligation
      product of cinnamaldehyde (cinALD) with activated acetaldehyde, mediated by
      pyruvate decarboxylases, could be identified as cinnamyl methyl ketone providing
      a new route for the biosynthesis of precursors, such as (2S,3R) 5-phenylpent-4
      ene-2,3-diol, necessary for the chemical synthesis of specific biologically
      active drugs such as daunomycin.

PMID- 29186482
TI  - ALR encoding dCMP deaminase is critical for DNA damage repair, cell cycle
      progression and plant development in rice.
AB  - Deoxycytidine monophosphate deaminase (dCMP deaminase, DCD) is crucial to the
      production of dTTP needed for DNA replication and damage repair. However, the
      effect of DCD deficiency and its molecular mechanism are poorly understood in
      plants. Here, we isolated and characterized a rice albinic leaf and growth
      retardation (alr) mutant that is manifested by albinic leaves, dwarf stature and
      necrotic lesions. Map-based cloning and complementation revealed that ALR encodes
      a DCD protein. OsDCD was expressed ubiquitously in all tissues. Enzyme activity
      assays showed that OsDCD catalyses conversion of dCMP to dUMP, and the DeltaDCD
      protein in the alr mutant is a loss-of-function protein that lacks binding
      ability. We report that alr plants have typical DCD-mediated imbalanced dNTP
      pools with decreased dTTP; exogenous dTTP recovers the wild-type phenotype. A
      comet assay and Trypan Blue staining showed that OsDCD deficiency causes
      accumulation of DNA damage in the alr mutant, sometimes leading to cell
      apoptosis. Moreover, OsDCD deficiency triggered cell cycle checkpoints and
      arrested cell progression at the G1/S-phase. The expression of nuclear and
      plastid genome replication genes was down-regulated under decreased dTTP, and
      together with decreased cell proliferation and defective chloroplast development
      in the alr mutant this demonstrated the molecular and physiological roles of DCD
      mediated dNTP pool balance in plant development.

PMID- 29186483
TI  - Eukaryotic-like Kinase Expression in Enterohemorrhagic Escherichia coli:
      Potential for Enhancing Host Aggressive Inflammatory Response.
AB  - Enterohemorrhagic Escherichia coli (EHEC) or other attaching/effacing pathogen
      infections often cause host intestinal inflammation and pathology, which is
      thought to result in part from a host aggressive innate immune response. However,
      few effectors that play an important role in this pathology change have been
      reported. In this study, we discovered a previously unknown EHEC effector, Stk
      (putative serine/threonine kinase), which induces host aggressive inflammatory
      response during EHEC infection. Interestingly, homologous proteins of Stk are
      widely distributed in many pathogens. After translocating into the infected host
      cells, Stk efficiently phosphorylates IkappaBalpha and activates the NF-kappaB
      pathway. In EHEC-infected mice, Stk increases serum keratinocyte-derived cytokine
      (KC) levels and hyperactivates the inflammatory response of the colon,
      intensifying pathological injury of the colon. The virulence of Stk is based on
      its eukaryotic-like kinase activity. In conclusion, our data suggest that Stk is
      a new effector that induces the host aggressive inflammatory response during EHEC
      infection.

PMID- 29186484
TI  - Development of a resource allocation formula for substance misuse treatment
      services.
AB  - Background: Funding for substance misuse services comprises one-third of Public
      Health spend in England. The current allocation formula contains adjustments for
      actual activity, performance and need, proxied by the Standardized Mortality
      Ratio for under-75s (SMR < 75). Additional measures, such as deprivation, may
      better identify differential service need. Methods: We developed an age
      standardized and an age-stratified model (over-18s, under-18s), with the outcome
      of expected/actual cost at postal sector/Local Authority level. A third, person
      based model incorporated predictors of costs at the individual level. Each model
      incorporated both needs and supply variables, with the relative effects of their
      inclusion assessed. Results: Mean estimated annual cost (2013/14) per English
      Local Authority area was L5 032 802 (sd: 3 951 158). Costs for drug misuse
      treatment represented the majority (83%) of costs. Models achieved adjusted R
      squared values of 0.522 (age-standardized), 0.533 (age-stratified over-18s),
      0.232 (age-stratified under-18s) and 0.470 (person-based). Conclusion:
      Improvements can be made to the existing resource allocation formulae to better
      reflect population need. The person-based model permits inclusion of a range of
      needs variables, in addition to strong predictors of cost based on the receipt of
      treatment in the previous year. Adoption of this revised person-based formula for
      substance misuse would shift resources towards more deprived areas.

PMID- 29186486
TI  - Long-read sequence assembly of the firefly Pyrocoelia pectoralis genome.
AB  - Background: Fireflies are a family of insects within the beetle order Coleoptera,
      or winged beetles, and they are one of the most well-known and loved insect
      species because of their bioluminescence. However, the firefly is in danger of
      extinction because of the massive destruction of its living environment. In order
      to improve the understanding of fireflies and protect them effectively, we
      sequenced the whole genome of the terrestrial firefly Pyrocoelia pectoralis.
      Findings: Here, we developed a highly reliable genome resource for the
      terrestrial firefly Pyrocoelia pectoralis (E. Oliv., 1883; Coleoptera:
      Lampyridae) using single molecule real time (SMRT) sequencing on the PacBio
      Sequel platform. In total, 57.8 Gb of long reads were generated and assembled
      into a 760.4-Mb genome, which is close to the estimated genome size and covered
      98.7% complete and 0.7% partial insect Benchmarking Universal Single-Copy
      Orthologs. The k-mer analysis showed that this genome is highly heterozygous.
      However, our long-read assembly demonstrates continuousness with a contig N50
      length of 3.04 Mb and the longest contig length of 13.69 Mb. Furthermore, 135 589
      SSRs and 341 Mb of repeat sequences were detected. A total of 23 092 genes were
      predicted; 88.44% of genes were annotated with one or more related functions.
      Conclusions: We assembled a high-quality firefly genome, which will not only
      provide insights into the conservation and biodiversity of fireflies, but also
      provide a wealth of information to study the mechanisms of their sexual
      communication, bio-luminescence, and evolution.

PMID- 29186485
TI  - Indications and practical approach to non-invasive ventilation in acute heart
      failure.
AB  - In acute heart failure (AHF) syndromes significant respiratory failure (RF) is
      essentially seen in patients with acute cardiogenic pulmonary oedema (ACPE) or
      cardiogenic shock (CS). Non-invasive ventilation (NIV), the application of
      positive intrathoracic pressure through an interface, has shown to be useful in
      the treatment of moderate to severe RF in several scenarios. There are two main
      modalities of NIV: continuous positive airway pressure (CPAP) and pressure
      support ventilation (NIPSV) with positive end expiratory pressure. Appropriate
      equipment and experience is needed for NIPSV, whereas CPAP may be administered
      without a ventilator, not requiring special training. Both modalities have shown
      to be effective in ACPE, by a reduction of respiratory distress and the
      endotracheal intubation rate compared to conventional oxygen therapy, but the
      impact on mortality is less conclusive. Non-invasive ventilation is also
      indicated in patients with AHF associated to pulmonary disease and may be
      considered, after haemodynamic stabilization, in some patients with CS. There are
      no differences in the outcomes in the studies comparing both techniques, but CPAP
      is a simpler technique that may be preferred in low-equipped areas like the pre
      hospital setting, while NIPSV may be preferable in patients with significant
      hypercapnia. The new modality 'high-flow nasal cannula' seems promising in cases
      of AHF with less severe RF. The correct selection of patients and interfaces,
      early application of the technique, the achievement of a good synchrony between
      patients and the ventilator avoiding excessive leakage, close monitoring,
      proactive management, and in some cases mild sedation, may warrant the success of
      the technique.

PMID- 29186487
TI  - Epizoic Fauna Survey on Phyllostomid Bats (Chiroptera: Phyllostomidae) in a
      Shaded Coffee Plantation of Southeastern Chiapas, Mexico.
AB  - This is the first complete assessment of the ectoparasite fauna on phyllostomid
      bats in a shaded coffee plantation in Mexico. The study was carried out at Finca
      San Carlos, in the municipality of Tapachula, southeastern Chiapas, Mexico. The
      bats were captured over three consecutive nights every month, from December 2005
      to November 2006, using four mist nets. We captured 192 phyllostomid bats,
      representing 18 species, upon which 1,971 ectoparasites, belonging to 11 families
      and 65 species, were found. We found that 160 of the 192 captured bats were hosts
      to ectoparasites, giving an infestation prevalence of 83.3%. Of the 65
      ectoparasitic species, 14 were classified as monoxenous and 17 as stenoxenous.
      More ectoparasites were recorded in the dry season (n = 1,439) than the wet
      season (n = 532), and we recorded some families of ectoparasite on particular
      areas of the bat body. An ordination of bat species, based on their ectoparasitic
      species community structure, formed groups at the subfamily level or lower
      taxonomic categories. We suggest that the close ectoparasite-host relationships
      could be examined as an additional tool to elucidate the taxonomic relationships
      between the hosts.

PMID- 29186489
TI  - Challenges to tuberculosis control in Angola: the narrative of medical
      professionals.
AB  - Background: There is a tuberculosis (TB) epidemic in Angola that has been getting
      worse for more than a decade despite the active implementation of the DOTS
      strategy. The aim of this study was to directly interrogate healthcare workers
      involved in TB control on what they consider to be the drivers of the TB epidemic
      in Angola. Methods: Twenty four in-depth qualitative interviews were conducted
      with medical staff working in this field in the provinces of Luanda and Benguela.
      Results: The healthcare professionals see the migrant working poor as a
      particular problem for the control of TB. These migrants are constructed as
      'Rural People' and are seen as non-compliant and late-presenting. This is a
      stigmatized and marginal group contending with the additional stigma associated
      with TB infection. The healthcare professionals interviewed also see the
      interruption of treatment and self-medication generally as a better explanation
      for the TB epidemic than urbanization or lack of medication. Conclusions: The
      local narrative is in contrast to previous explanations used elsewhere in the
      developing world. To be effective policy must recognize the local issues of the
      migrant workforce, interruption of treatment and the stigma associated with TB in
      Angola.

PMID- 29186488
TI  - A putative R3 MYB repressor is the candidate gene underlying atroviolacium, a
      locus for anthocyanin pigmentation in tomato fruit.
AB  - Anthocyanins are potential health-promoting compounds in the human diet. The atv
      (atroviolacium) locus, derived from the wild tomato species Solanum cheesmaniae,
      has been shown to enhance anthocyanin pigmentation in tomato fruit when it co
      exists with either the Aft (Anthocyanin fruit) or the Abg (Aubergine) locus. In
      the present study, the atv locus was fine-mapped to an approximately 5.0-kb
      interval on chromosome 7. A putative R3 MYB repressor was identified in this
      interval and is hereby designated as SlMYBATV. The allele of SlMYBATV underlying
      the atv locus harbored a 4-bp insertion in its coding region, which is predicted
      to result in a frame-shift and premature protein truncation. The other candidate
      R3 MYB and R2R3 MYB repressors of anthocyanin biosynthesis were also identified
      in tomato via a genome-wide search. Transcriptional analysis showed that most of
      the structural genes and several regulatory genes of anthocyanin biosynthesis
      were up-regulated in the tomato SlMYBATV mutant lines. These findings may
      facilitate the elucidation of the molecular mechanisms underlying anthocyanin
      pigmentation in tomato fruit and help in the marker-assisted selection of
      anthocyanin-enriched tomato cultivars.

PMID- 29186490
TI  - MEASUREMENTS OF RADIATION EXPOSURE OF RADIOGRAPHY STUDENTS DURING THEIR CLINICAL
      TRAINING USING THERMOLUMINESCENT DOSIMETRY.
AB  - Radiation dose monitoring for radiography students during clinical training is
      necessary to demonstrate the extent of radiation protection issues present, as
      well as to instill in them an awareness of safe practices that they will carry
      with them throughout their careers. The study assess the radiation dose incurred
      by the undergraduate during clinical training. 312 students were monitored using
      (thermoluminescence dosimetry) between 2009 and 2015. The results establish that
      the radiation dose received by the students is well below the dose recommended by
      national and international authorities. Findings indicate that the dose did not
      reach the value of 1 mSv, which indicate that current radiation protection
      measures are acceptable and there was no risk of overexposure, as well as
      reinforces the importance of nuturing a culture of radiation protection and
      provides evidence to students that their future as professionals will be a safe
      one.

PMID- 29186491
TI  - CLAMP - a toolkit for efficiently building customized clinical natural language
      processing pipelines.
AB  - Existing general clinical natural language processing (NLP) systems such as
      MetaMap and Clinical Text Analysis and Knowledge Extraction System have been
      successfully applied to information extraction from clinical text. However, end
      users often have to customize existing systems for their individual tasks, which
      can require substantial NLP skills. Here we present CLAMP (Clinical Language
      Annotation, Modeling, and Processing), a newly developed clinical NLP toolkit
      that provides not only state-of-the-art NLP components, but also a user-friendly
      graphic user interface that can help users quickly build customized NLP pipelines
      for their individual applications. Our evaluation shows that the CLAMP default
      pipeline achieved good performance on named entity recognition and concept
      encoding. We also demonstrate the efficiency of the CLAMP graphic user interface
      in building customized, high-performance NLP pipelines with 2 use cases,
      extracting smoking status and lab test values. CLAMP is publicly available for
      research use, and we believe it is a unique asset for the clinical NLP community.

PMID- 29186492
TI  - Mechanisms of acid-base regulation in peritoneal dialysis.
AB  - Background: Peritoneal dialysis (PD) contributes to restore acid-base homeostasis
      in patients with end-stage renal disease. The transport pathways for buffers and
      carbon dioxide (CO2) across the peritoneal membrane remain poorly understood.
      Methods: Combining well-established PD protocols, whole-body plethysmography and
      renal function studies in mice, we investigated molecular mechanisms of acid-base
      regulation in PD, including the potential role of the water channel aquaporin-1
      (AQP1). Results: After instillation in peritoneal cavity, the pH of acidic
      dialysis solutions increased within minutes to rapidly equilibrate with blood pH,
      whereas the neutral pH of biocompatible solutions remained constant. Predictions
      from the three-pore model of peritoneal transport suggested that local production
      of HCO3- accounts at least in part for the changes in intraperitoneal pH observed
      with acidic solutions. Carbonic anhydrase (CA) isoforms were evidenced in the
      peritoneal membrane and their inhibition with acetazolamide significantly
      decreased local production of HCO3- and delayed changes in intraperitoneal pH. On
      the contrary, genetic deletion of AQP1 had no effect on peritoneal transport of
      buffers and diffusion of CO2. Besides intraperitoneal modifications, the use of
      acidic dialysis solutions enhanced acid excretion both at pulmonary and renal
      levels. Conclusions: These findings suggest that changes in intraperitoneal pH
      during PD are mediated by bidirectional buffer transport and by CA-mediated
      production of HCO3- in the membrane. The use of acidic solutions enhances acid
      excretion through respiratory and renal responses, which should be considered in
      patients with renal failure.

PMID- 29186493
TI  - A Molecular Survey of Rickettsias in Shelter Dogs and Distribution of
      Rhipicephalus sanguineus (Acari: Ixodidae) sensu lato in Southeast Turkey.
AB  - Canine tick-borne pathogens are the source of emerging diseases and have
      important zoonotic relevance. Dogs play a major role in the transmission of
      several zoonotic tick-borne pathogens, as reservoirs and/or sentinels. To
      simultaneously detect Anaplasma and Ehrlichia species, a reverse line blot assay
      was conducted on 219 blood samples collected from autochthonous asymptomatic
      shelter dogs. One hundred and three (47.0%, CI 40.3-53.9) dogs were positive for
      one or both rickettsial pathogens. Seventy-one (32.4%, CI 26.3-39.0) dogs were
      infected with Anaplasma platys and 23 (10.5%, CI 6.8-15.3) with Ehrlichia canis.
      Concurrent infection with A. platys and E. canis was detected in nine (4.1%, CI
      1.9-7.6) dogs. Partial sequences of the 16S ribosomal RNA gene shared 100%
      identity with the corresponding published sequences for A. platys and E. canis.
      Infection with Anaplasma phagocytophilum was not detected in the examined dogs.
      In total, 1018 (range 1-70, mean intensity 13.1, mean abundance 4.6)
      Rhipicephalus sanguineus (Latreille) (Acari: Ixodidae) sensu lato ticks (45.7%
      nymphs, 54.3% adults) were collected from the dogs. There was no significant
      association between Anaplasma/Ehrlichia infection and dog sex or age, but a
      significant correlation was found between rickettsia infection and presence of R.
      sanguineus. Improved tick control strategies to reduce the risk of these
      pathogens spreading among dogs and humans are needed in the region.

PMID- 29186494
TI  - Mitral valve repair in Barlow's disease with bileaflet prolapse: the effect of
      annular stabilization on functional mitral valve leaflet prolapse.
AB  - OBJECTIVES: Barlow's disease is the most severe form of degenerative mitral valve
      disease, commonly characterized by bileaflet prolapse. Abnormal mitral annular
      dynamics is typically present and results in functional prolapse of the mitral
      leaflets that may be addressed with annular stabilization alone. METHODS: Between
      January 2001 and December 2015, 128 patients with Barlow's disease and bileaflet
      prolapse underwent valve repair. This included anterior mitral valve leaflet
      (AMVL) repair in 70 patients, whereas 58 patients were identified as having
      functional prolapse and underwent no specific AMVL repair. During the course of
      the study, the proportion of patients undergoing specific AMVL repair decreased
      (77% in the first and 33% in the second 64 patients). Semirigid ring annuloplasty
      was performed in all cases. The median clinical and echocardiographic follow-up
      duration was 6.5 years [interquartile range (IQR) 2.9-10.5 years; 93.9% complete]
      and 4.7 years (IQR 2.2-10.2 years; 94.4% complete), respectively. RESULTS: Early
      mortality was 1.6%. Postoperative echocardiogram demonstrated no residual mitral
      regurgitation in all but 1 patient (AMVL repair group). There was no significant
      difference in the overall survival rate at 6 years after operation between both
      groups. At 6 years, the freedom from recurrent >=Grade 2+ mitral regurgitation
      rate was 90.7% (IQR 82.9-98.5%) and 89.1% (IQR 75.8-100%) for patients with and
      patients with no AMVL repair, respectively (P = 0.43). Three patients required
      late mitral valve reintervention, all from the AMVL repair group. CONCLUSIONS:
      Annular stabilization can effectively resolve the functional prolapse of the
      AMVL. Careful discrimination between functional and true AMVL prolapse allows for
      a technically less challenging operation that provides excellent repair
      durability.

PMID- 29186495
TI  - Sugar metabolism reprogramming in a non-climacteric bud mutant of a climacteric
      plum fruit during development on the tree.
AB  - We investigated sugar metabolism in leaves and fruits of two Japanese plum
      (Prunus salicina Lindl.) cultivars, the climacteric Santa Rosa and its bud sport
      mutant the non-climacteric Sweet Miriam, during development on the tree. We
      previously characterized differences between the two cultivars. Here, we
      identified key sugar metabolic pathways. Pearson coefficient correlations of
      metabolomics and transcriptomic data and weighted gene co-expression network
      analysis (WGCNA) of RNA sequencing (RNA-Seq) data allowed the identification of
      11 key sugar metabolism-associated genes: sucrose synthase, sucrose phosphate
      synthase, cytosolic invertase, vacuolar invertase, invertase inhibitor, alpha
      galactosidase, beta-galactosidase, galactokinase, trehalase, galactinol synthase,
      and raffinose synthase. These pathways were further assessed and validated
      through the biochemical characterization of the gene products and with metabolite
      analysis. Our results demonstrated the reprogramming of sugar metabolism in both
      leaves and fruits in the non-climacteric plum, which displayed a shift towards
      increased sorbitol synthesis. Climacteric and non-climacteric fruits showed
      differences in their UDP-galactose metabolism towards the production of galactose
      and raffinose, respectively. The higher content of galactinol, myo-inositol,
      raffinose, and trehalose in the non-climacteric fruits could improve the ability
      of the fruits to cope with the oxidative processes associated with fruit
      ripening. Overall, our results support a relationship between sugar metabolism,
      ethylene, and ripening behavior.

PMID- 29186496
TI  - Anterior Cingulate Cortex TDP-43 Pathology in Sporadic Amyotrophic Lateral
      Sclerosis.
AB  - Neuronal constituents of the human anterior cingulate cortex displayed
      morphological changes related to the 43-kDa transactive response DNA-binding
      protein (TDP-43) in advanced pathological stages of sporadic amyotrophic lateral
      sclerosis (sALS). By using nonphosphorylation-dependent TDP-43
      immunocytochemistry, it was seen that the changes in susceptible pyramidal cells
      of the superficial cellular layers II-IIIab differed from those in the deep
      layers IIIc-Vb: A complete loss of nuclear TDP-43 expression (i.e. nuclear
      clearing) in the small projection neurons of layers II-IIIab was consistently
      accompanied by the development of somatic skein-like TDP-43-immunopositive
      inclusions. In contrast, in the large pyramidal cells of layers IIIc-Vb and von
      Economo neurons of layer Vb, skein-like inclusions were lacking or, when
      aggregated TDP-43 was present, the aggregates presented as dash-like TDP-43
      immunopositive particles in the vicinity of the cell nucleus. The cytoskeleton of
      projection neurons in layers II-IIIab is neurofilament-sparse in contrast to that
      of the large neurons in layers IIIc-Vb, which are rich in neurofilaments and also
      heat shock proteins that function as their molecular chaperones. The disparities
      between the two neuronal populations may contribute to the two differing
      immunocytochemical profiles reported here. Some implications of the findings for
      the pathogenesis and progression of TDP-43 pathology in sALS are discussed.

PMID- 29186497
TI  - For as Long as Necessary: Examining 30 years of MSD's Focus on Achieving
      Elimination of Onchocerciasis and Lymphatic Filariasis.
AB  - Established by MSD, also known as Merck & Co., Inc., Kenilworth, NJ USA in 1987,
      the Mectizan Donation Program (MDP) is the longest running disease-specific
      program of its kind. Initially aimed at control of onchocerciasis (river
      blindness), the company expanded its commitment through the MDP in 1998 to
      include lymphatic filariasis (LF). Both diseases are now candidates for
      elimination and the company is engaged in several global partnerships to help
      advance towards that goal. To support the steadily growing demand from country
      led disease elimination programs, the company has put in place several
      administrative and operational improvements. In addition, the company is involved
      'beyond the pill', including making financial and management contributions to
      partners such as the END Fund and the Expanded Special Project to Eliminate NTDs
      (ESPEN) to support the technical needs of elimination programs. While the time
      bound elimination targets are challenging, clear progress is being made for both
      onchocerciasis and LF, with several national and subnational areas in Latin
      America and Africa having stopped transmission of one or both diseases. The
      company's donation of Mectizan and contributions of financial, management and
      technical resources reflect the company's long-standing commitment to pursue
      inventive ways to expand and enhance access to medicine. Continued support from
      MSD and other partners will enable countries to advance towards their elimination
      targets for LF and onchocerciasis.

PMID- 29186499
TI  - Collaborating for oral health in support of vulnerable older people: co
      production of oral health training in care homes.
AB  - Background: In recent years, the value of co-production has become embedded in
      the social care agenda. Care home residents are at significantly higher risk of
      dental diseases and often rely on the care team for support. It is therefore
      vital that staff are trained and confident in delivering evidence based oral care
      to their clients. Methods: Three London care homes co-produced a pilot oral
      health training programme, informed by in-depth interviews and group discussions.
      The initiative was evaluated using pre/post-questionnaires of carers and semi
      structured interviews of managers and the dental teams. Results: Two care homes
      were available for delivery of the programme, which resulted in training of 64%
      (n = 87) of care staff. The training programme involved videos and resources and
      was delivered flexibly with the support of an oral health educator and a dental
      therapist. There was an improvement in knowledge and self-reported confidence
      post-training; however, only 54% (n = 45) completed the post-training
      questionnaire. Conclusions: This study suggests that co-production of an oral
      care training package for care home staff, is possible and welcome, but
      challenging in this complex and changing environment. Further work is needed to
      explore the feasibility, sustainability and impact of doing so.

PMID- 29186498
TI  - The Medicago truncatula GRAS protein RAD1 supports arbuscular mycorrhiza
      symbiosis and Phytophthora palmivora susceptibility.
AB  - The roots of most land plants are colonized by symbiotic arbuscular mycorrhiza
      (AM) fungi. To facilitate this symbiosis, plant genomes encode a set of genes
      required for microbial perception and accommodation. However, the extent to which
      infection by filamentous root pathogens also relies on some of these genes
      remains an open question. Here, we used genome-wide association mapping to
      identify genes contributing to colonization of Medicago truncatula roots by the
      pathogenic oomycete Phytophthora palmivora. Single-nucleotide polymorphism (SNP)
      markers most significantly associated with plant colonization response were
      identified upstream of RAD1, which encodes a GRAS transcription regulator first
      negatively implicated in root nodule symbiosis and recently identified as a
      positive regulator of AM symbiosis. RAD1 transcript levels are up-regulated both
      in response to AM fungus and, to a lower extent, in infected tissues by P.
      palmivora where its expression is restricted to root cortex cells proximal to
      pathogen hyphae. Reverse genetics showed that reduction of RAD1 transcript levels
      as well as a rad1 mutant are impaired in their full colonization by AM fungi as
      well as by P. palmivora. Thus, the importance of RAD1 extends beyond symbiotic
      interactions, suggesting a general involvement in M. truncatula microbe-induced
      root development and interactions with unrelated beneficial and detrimental
      filamentous microbes.

PMID- 29186500
TI  - Modeling the factors associating with health-related habits among Japanese
      students.
AB  - The aim of the present study was to clarify the structural relationship between
      health-related habits and psychosocial factors during adolescence/early
      adulthood. An anonymous, self-administered questionnaire was provided to 1141
      third- and fourth-year students at eight academic departments from six
      universities in regional Japanese cities. Surveys included items addressing
      participants' demographic characteristics, psychosocial factors (individual-level
      social capital, self-efficacy, mental health (from health-related quality of life
      SF-36v2), and sense of coherence (SOC)), and health-related habits. A multiple
      indicator analysis based on structural equation modeling was conducted to examine
      the structural relationship between health-related habits and these factors.
      Valid responses were obtained from 952 participants. The final model demonstrated
      a high level of goodness of fit. While the path from SOC to health-related habits
      was significant, those from self-efficacy to health-related habits and from
      mental health to health-related habits were not significant. The path coefficient
      from SOC to health-related habits was greater than the path coefficient from
      background characteristics. In the multiple population comparison that considered
      gender, a nearly identical model was supported for men and women. Psychosocial
      factors related to health-related habits were social capital, self-efficacy,
      mental health, and SOC. Furthermore, it was suggested that SOC functions as an
      intervening factor for maintaining a healthy lifestyle. It was observed that
      individual psychosocial factors influence health-related habits more than their
      background characteristics. Findings highlight that supporting the building of
      social relationships and social environments is essential to promote a healthy
      lifestyle among university students.

PMID- 29186502
TI  - Ablation of atrial fibrillation: surgery may show the way.

PMID- 29186503
TI  - MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes
      nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects.
AB  - MINTbase is a repository that comprises nuclear and mitochondrial tRNA-derived
      fragments ('tRFs') found in multiple human tissues. The original version of
      MINTbase comprised tRFs obtained from 768 transcriptomic datasets. We used our
      deterministic and exhaustive tRF mining pipeline to process all of The Cancer
      Genome Atlas datasets (TCGA). We identified 23 413 tRFs with abundance of >= 1.0
      reads-per-million (RPM). To facilitate further studies of tRFs by the community,
      we just released version 2.0 of MINTbase that contains information about 26 531
      distinct human tRFs from 11 719 human datasets as of October 2017. Key new
      elements include: the ability to filter tRFs on-the-fly by minimum abundance
      thresholding; the ability to filter tRFs by tissue keywords; easy access to
      information about a tRF's maximum abundance and the datasets that contain it; the
      ability to generate relative abundance plots for tRFs across cancer types and
      convert them into embeddable figures; MODOMICS information about modifications of
      the parental tRNA, etc. Version 2.0 of MINTbase contains 15x more datasets and
      nearly 4x more distinct tRFs than the original version, yet continues to offer
      fast, interactive access to its contents. Version 2.0 is available freely at
      http://cm.jefferson.edu/MINTbase/.

PMID- 29186504
TI  - No evidence of neurocognitive adverse events associated with alirocumab treatment
      in 3340 patients from 14 randomized Phase 2 and 3 controlled trials: a meta
      analysis of individual patient data.
AB  - Aims: Despite patient reports of neurocognitive disorders with lipid-lowering
      treatments (LLTs), large clinical trials have found no significant association
      between neurocognitive disorders and LLTs. We assessed incidence of
      neurocognitive treatment-emergent adverse events (TEAEs) from 14 Phase 2 and 3
      trials of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor
      alirocumab. Methods and results: Patients (most on background maximally tolerated
      statin) received alirocumab 75/150 mg every 2 weeks (n = 3340; 4029 patient-years
      of exposure), placebo (n = 1276), or ezetimibe (n = 618). Data were pooled by the
      control used. Neurocognitive TEAEs were reported by 22 (0.9%) alirocumab-treated
      patients vs. 9 (0.7%) with placebo in placebo-controlled trials [hazard ratio
      (HR) 1.24, 95% confidence interval (CI) 0.57-2.68] and 10 (1.2%) with alirocumab
      vs. 8 (1.3%) with ezetimibe in ezetimibe-controlled trials (HR 0.81, 95% CI 0.32
      2.08). Rates of neurocognitive TEAEs were similar in patients receiving
      alirocumab with LDL cholesterol (LDL-C) levels <25 mg/dL (<0.65 mmol/L; n =
      5/839; 0.6%; 0.5/100 patient-years) vs. >=25 mg/dL (n = 26/2501; 1.0%; 0.8/100
      patient-years). One patient (0.1%; ezetimibe-controlled pool) receiving
      alirocumab had a neurocognitive TEAE leading to discontinuation vs. two (0.2%)
      patients receiving placebo and three (0.4%) patients receiving ezetimibe.
      Neurocognitive TEAE incidence was also similar between alirocumab and controls
      when stratified by age. Conclusions: Neurocognitive TEAE incidences were low
      (<=1.2%), with no significant differences between alirocumab vs. controls up to
      104 weeks. No association was found between neurocognitive TEAEs and LDL-C <25
      mg/dL based on the completed Phase 2 and 3 trials examined, although long-term
      effects of very low LDL-C levels induced by PCSK9 inhibitors are currently
      unknown.

PMID- 29186505
TI  - Robust detection of chromosomal interactions from small numbers of cells using
      low-input Capture-C.
AB  - Chromosome conformation capture (3C) techniques are crucial to understanding
      tissue-specific regulation of gene expression, but current methods generally
      require large numbers of cells. This hampers the investigation of chromatin
      architecture in rare cell populations. We present a new low-input Capture-C
      approach that can generate high-quality 3C interaction profiles from 10 000-20
      000 cells, depending on the resolution used for analysis. We also present a PCR
      free, sequencing-free 3C technique based on NanoString technology called C
      String. By comparing C-String and Capture-C interaction profiles we show that the
      latter are not skewed by PCR amplification. Furthermore, we demonstrate that
      chromatin interactions detected by Capture-C do not depend on the degree of cross
      linking by performing experiments with varying formaldehyde concentrations.

PMID- 29186501
TI  - The Amygdala as a Locus of Pathologic Misfolding in Neurodegenerative Diseases.
AB  - Over the course of most common neurodegenerative diseases the amygdala
      accumulates pathologically misfolded proteins. Misfolding of 1 protein in aged
      brains often is accompanied by the misfolding of other proteins, suggesting
      synergistic mechanisms. The multiplicity of pathogenic processes in human
      amygdalae has potentially important implications for the pathogenesis of
      Alzheimer disease, Lewy body diseases, chronic traumatic encephalopathy, primary
      age-related tauopathy, and hippocampal sclerosis, and for the biomarkers used to
      diagnose those diseases. Converging data indicate that the amygdala may represent
      a preferential locus for a pivotal transition from a relatively benign clinical
      condition to a more aggressive disease wherein multiple protein species are
      misfolded. Thus, understanding of amygdalar pathobiology may yield insights
      relevant to diagnoses and therapies; it is, however, a complex and imperfectly
      defined brain region. Here, we review aspects of amygdalar anatomy, connectivity,
      vasculature, and pathologic involvement in neurodegenerative diseases with
      supporting data from the University of Kentucky Alzheimer's Disease Center
      autopsy cohort. Immunohistochemical staining of amygdalae for Abeta, Tau, alpha
      synuclein, and TDP-43 highlight the often-coexisting pathologies. We suggest that
      the amygdala may represent an "incubator" for misfolded proteins and that it is
      possible that misfolded amygdalar protein species are yet to be discovered.

PMID- 29186506
TI  - Identification of large rearrangements in cancer genomes with barcode linked
      reads.
AB  - Large genomic rearrangements involve inversions, deletions and other structural
      changes that span Megabase segments of the human genome. This category of genetic
      aberration is the cause of many hereditary genetic disorders and contributes to
      pathogenesis of diseases like cancer. We developed a new algorithm called ZoomX
      for analysing barcode-linked sequence reads-these sequences can be traced to
      individual high molecular weight DNA molecules (>50 kb). To generate barcode
      linked sequence reads, we employ a library preparation technology (10X Genomics)
      that uses droplets to partition and barcode DNA molecules. Using linked read data
      from whole genome sequencing, we identify large genomic rearrangements, typically
      greater than 200kb, even when they are only present in low allelic fractions. Our
      algorithm uses a Poisson scan statistic to identify genomic rearrangement
      junctions, determine counts of junction-spanning molecules and calculate a
      Fisher's exact test for determining statistical significance for somatic
      aberrations. Utilizing a well-characterized human genome, we benchmarked this
      approach to accurately identify large rearrangement. Subsequently, we
      demonstrated that our algorithm identifies somatic rearrangements when present in
      lower allelic fractions as occurs in tumors. We characterized a set of complex
      cancer rearrangements with multiple classes of structural aberrations and with
      possible roles in oncogenesis.

PMID- 29186507
TI  - Pyridylhydroxybutyl and pyridyloxobutyl DNA phosphate adduct formation in rats
      treated chronically with enantiomers of the tobacco-specific nitrosamine
      metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
AB  - The tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) is metabolically converted to 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanol (NNAL) in a reaction which is both stereoselective and reversible. NNAL
      is also a lung carcinogen, with both (R)-NNAL and (S)-NNAL inducing a high
      incidence of lung tumours in rats. Both NNAL and NNK undergo metabolic activation
      to intermediates which react with DNA to form pyridylhydroxybutyl and
      pyridyloxobutyl DNA adducts, respectively. DNA adduct formation by NNAL and NNK
      is an important step in their mechanisms of carcinogenesis. In this study, we
      quantified both pyridylhydroxybutyl and pyridyloxobutyl DNA phosphate adducts in
      the lung of rats treated with 5 ppm of (R)-NNAL or (S)-NNAL in drinking water for
      10, 30, 50 and 70 weeks. In (R)-NNAL-treated rats, the pyridylhydroxybutyl and
      pyridyloxobutyl phosphate adducts were 4530-6920 fmol/mg DNA and 46-175 fmol/mg
      DNA, accounting for 45-51% and 0.3-1% of the total measured DNA phosphate and
      base adducts, respectively. In (S)-NNAL-treated rats, the two types of phosphate
      adducts were 3480-4180 fmol/mg DNA and 1180-4650 fmol/mg DNA, accounting for 30
      36% and 11-38% of the total adducts, respectively. Distinct patterns of adduct
      formation were observed, with higher levels of NNAL-derived pyridylhydroxybutyl
      phosphate adducts and lower levels of NNK-derived pyridyloxobutyl phosphate
      adducts in the (R)-NNAL treatment group than the (S)-NNAL group. The persistence
      and increase over time of certain pyridylhydroxybutyl phosphate adducts over the
      course of the study suggest that these adducts could be useful biomarkers of
      chronic exposure to NNAL and NNK. The results of this study provide important new
      information regarding DNA damage by NNAL and NNK, and contribute to understanding
      mechanisms of tobacco-related carcinogenesis.

PMID- 29186508
TI  - Are all certified EHRs created equal? Assessing the relationship between EHR
      vendor and hospital meaningful use performance.
AB  - Objective: The federal electronic health record (EHR) certification process was
      intended to ensure a baseline level of system quality and the ability to support
      meaningful use criteria. We sought to assess whether there was variation across
      EHR vendors in the degree to which hospitals using products from those vendors
      were able to achieve high levels of performance on meaningful use criteria.
      Materials and Methods: We created a cross-sectional national hospital sample from
      the Office of the National Coordinator for Health Information Technology EHR
      Products Used for Meaningful Use Attestation public use file and the Centers for
      Medicare & Medicaid Services Medicare EHR Incentive Program Eligible Hospitals
      public use file. We used regression models to assess the relationship between
      vendor and hospital performance on 6 Stage 2 Meaningful Use criteria, controlling
      for hospital characteristics. We also calculated how much variation in
      performance is explained by vendor choice. Results: We found significant
      associations between specific vendor and level of hospital performance for all 6
      meaningful use criteria. Epic was associated with significantly higher
      performance on 5 of the 6 criteria; relationships for other vendors were mixed,
      with some associated with significantly worse performance on multiple criteria.
      EHR vendor choice accounted for between 7% and 34% of performance variation
      across the 6 criteria. Discussion: A nontrivial proportion of variation in
      hospital meaningful use performance is explained by vendor choice, and certain
      vendors are more often associated with better meaningful use performance than
      others. Our results suggest that policy-makers should improve the certification
      process by including more "real-world" scenario testing and provider feedback or
      ratings to reduce this variation. Hospitals can use these results to guide
      interactions with vendors. Conclusion: Vendor choice accounts for a meaningful
      proportion of variation in hospital meaningful use performance, and specific
      vendors are consistently associated with higher or lower performance across
      criteria.

PMID- 29186509
TI  - Moxifloxacin target site concentrations in patients with pulmonary TB utilizing
      microdialysis: a clinical pharmacokinetic study.
AB  - Background: Moxifloxacin is a second-line anti-TB drug that is useful in the
      treatment of drug-resistant TB. However, little is known about its target site
      pharmacokinetics. Lower drug concentrations at the infection site (i.e. in severe
      lung lesions including cavitary lesions) may lead to development and
      amplification of drug resistance. Improved knowledge regarding tissue penetration
      of anti-TB drugs will help guide drug development and optimize drug dosing.
      Methods: Patients with culture-confirmed drug-resistant pulmonary TB scheduled to
      undergo adjunctive surgical lung resection were enrolled in Tbilisi, Georgia.
      Five serum samples per patient were collected at different timepoints including
      at the time of surgical resection (approximately at Tmax). Microdialysis was
      performed in the ex vivo tissue immediately after resection. Non-compartmental
      analysis was performed and a tissue/serum concentration ratio was calculated.
      Results: Among the seven patients enrolled, the median moxifloxacin dose given
      was 7.7 mg/kg, the median age was 25.2 years, 57% were male and the median
      creatinine clearance was 95.4 mL/min. Most patients (71%) had suboptimal steady
      state serum Cmax (total drug) concentrations. The median free moxifloxacin serum
      concentration at time of surgical resection was 1.23 MUg/mL (range = 0.12-1.80)
      and the median free lung tissue concentration was 3.37 MUg/mL (range = 0.81
      5.76). The median free-tissue/free-serum concentration ratio was 3.20 (range =
      0.66-28.08). Conclusions: Moxifloxacin showed excellent penetration into diseased
      lung tissue (including cavitary lesions) among patients with pulmonary TB.
      Moxifloxacin lung tissue concentrations were higher than those seen in serum. Our
      findings highlight the importance of moxifloxacin in the treatment of MDR-TB and
      potentially any patient with pulmonary TB and severe lung lesions.

PMID- 29186510
TI  - The European Bioinformatics Institute in 2017: data coordination and integration.
AB  - The European Bioinformatics Institute (EMBL-EBI) supports life-science research
      throughout the world by providing open data, open-source software and analytical
      tools, and technical infrastructure (https://www.ebi.ac.uk). We accommodate an
      increasingly diverse range of data types and integrate them, so that biologists
      in all disciplines can explore life in ever-increasing detail. We maintain over
      40 data resources, many of which are run collaboratively with partners in 16
      countries (https://www.ebi.ac.uk/services). Submissions continue to increase
      exponentially: our data storage has doubled in less than two years to 120
      petabytes. Recent advances in cellular imaging and single-cell sequencing
      techniques are generating a vast amount of high-dimensional data, bringing to
      light new cell types and new perspectives on anatomy. Accordingly, one of our
      main focus areas is integrating high-quality information from bioimaging,
      biobanking and other types of molecular data. This is reflected in our deep
      involvement in Open Targets, stewarding of plant phenotyping standards (MIAPPE)
      and partnership in the Human Cell Atlas data coordination platform, as well as
      the 2017 launch of the Omics Discovery Index. This update gives a birds-eye view
      of EMBL-EBI's approach to data integration and service development as genomics
      begins to enter the clinic.

PMID- 29186511
TI  - An RNA polymerase II-associated TFIIF-like complex is indispensable for SL RNA
      gene transcription in Trypanosoma brucei.
AB  - Trypanosomes are protistan parasites that diverged early in evolution from most
      eukaryotes. Their streamlined genomes are packed with arrays of tandemly linked
      genes that are transcribed polycistronically by RNA polymerase (pol) II.
      Individual mRNAs are processed from pre-mRNA by spliced leader (SL) trans
      splicing and polyadenylation. While there is no strong evidence that general
      transcription factors are needed for transcription initiation at these gene
      arrays, a RNA pol II transcription pre-initiation complex (PIC) is formed on
      promoters of SLRNA genes, which encode the small nuclear SL RNA, the SL donor in
      trans splicing. The factors that form the PIC are extremely divergent orthologues
      of the small nuclear RNA-activating complex, TBP, TFIIA, TFIIB, TFIIH, TFIIE and
      Mediator. Here, we functionally characterized a heterodimeric complex of
      unannotated, nuclear proteins that interacts with RNA pol II and is essential for
      PIC formation, SL RNA synthesis in vivo, SLRNA transcription in vitro, and
      parasite viability. These functional attributes suggest that the factor
      represents TFIIF although the amino acid sequences are too divergent to firmly
      make this conclusion. This work strongly indicates that early-diverged
      trypanosomes have orthologues of each and every general transcription factor,
      requiring them for the synthesis of SL RNA.

PMID- 29186513
TI  - Projected impact of future climate on water-stress patterns across the Australian
      wheatbelt.
AB  - Drought frequently limits Australian wheat production, and the expected future
      increase in temperatures and rainfall variability will further challenge
      productivity. A modelling approach captured plant*environment*management
      interactions to simulate water-stress patterns experienced by wheat crops at
      representative locations across the Australian wheatbelt for 33 climate model
      projections, considering the 'business as usual' emission scenario RCP8.5. The
      results indicate that projections of future water-stress patterns are region
      specific. Significant variations in projected impacts were found across climate
      models, providing local ranges of uncertainty to consider in planning efforts.
      Most climate models projected an increase in the frequency of severe water-stress
      conditions in the Western area, the largest producing region, and fewer severe
      water stresses in other regions. Where found, reductions in water-stress
      conditions were largely due to shorter crop cycles (a result of warmer
      temperatures), increased water use efficiency (resulting from increased CO2
      levels), and, in some cases, increased local rainfall. Overall, simulations
      indicate that all areas of the Australian wheatbelt will continue to experience
      severe water-stress conditions (43.9, 42.6, and 40.2% for 2030, 2050, and 2070
      compared with 42.8% for 1990). Given projected frequencies of severe water stress
      and warmer conditions, efforts towards maintaining or improving yields are
      essential.

PMID- 29186512
TI  - DOFT and DOFTIP1 affect reproductive development in the orchid Dendrobium Chao
      Praya Smile.
AB  - FLOWERING LOCUS T (FT) in Arabidopsis encodes the florigen that moves from leaves
      to the shoot apical meristem to induce flowering, and this is partly mediated by
      FT-INTERACTING PROTEIN 1 (FTIP1). Although FT orthologs have been identified in
      some flowering plants, their endogenous roles in Orchidaceae, which is one of the
      largest families of flowering plants, are still largely unknown. In this study,
      we show that DOFT and DOFTIP1, the orchid orthologs of FT and FTIP1,
      respectively, play important roles in promoting flowering in the orchid
      Dendrobium Chao Praya Smile. Expression of DOFT and DOFTIP1 increases in whole
      plantlets during the transition from vegetative to reproductive development. Both
      transcripts are present in significant levels in reproductive organs, including
      inflorescence apices, stems, floral buds, and open flowers. Through successful
      generation of transgenic orchids, we have revealed that overexpression or down
      regulation of DOFT accelerates or delays flowering, respectively, while
      alteration of DOFT expression also greatly affects pseudobulb formation and
      flower development. In common with their counterparts in Arabidopsis and rice,
      DOFTIP1 interacts with DOFT and affects flowering time in orchids. Our results
      suggest that while DOFT and DOFTIP1 play evolutionarily conserved roles in
      promoting flowering, DOFT may have evolved with hitherto unknown functions
      pertaining to the regulation of storage organs and flower development in the
      Orchidaceae family.

PMID- 29186514
TI  - Permissive zones for the centromere-binding protein ParB on the Caulobacter
      crescentus chromosome.
AB  - Proper chromosome segregation is essential in all living organisms. In
      Caulobacter crescentus, the ParA-ParB-parS system is required for proper
      chromosome segregation and cell viability. The bacterial centromere-like parS DNA
      locus is the first to be segregated following chromosome replication. parS is
      bound by ParB protein, which in turn interacts with ParA to partition the ParB
      parS nucleoprotein complex to each daughter cell. Here, we investigated the
      genome-wide distribution of ParB on the Caulobacter chromosome using a
      combination of in vivo chromatin immunoprecipitation (ChIP-seq) and in vitro DNA
      affinity purification with deep sequencing (IDAP-seq). We confirmed two
      previously identified parS sites and discovered at least three more sites that
      cluster ~8 kb from the origin of replication. We showed that Caulobacter ParB
      nucleates at parS sites and associates non-specifically with ~10 kb flanking DNA
      to form a high-order nucleoprotein complex on the left chromosomal arm. Lastly,
      using transposon mutagenesis coupled with deep sequencing (Tn-seq), we identified
      a ~500 kb region surrounding the native parS cluster that is tolerable to the
      insertion of a second parS cluster without severely affecting cell viability. Our
      results demonstrate that the genomic distribution of parS sites is highly
      restricted and is crucial for chromosome segregation in Caulobacter.

PMID- 29186517
TI  - Renal replacement therapy intensity for acute kidney injury and recovery to
      dialysis independence: a systematic review and individual patient data meta
      analysis.
AB  - Background: There is no consensus whether higher intensity dose renal replacement
      therapy (RRT) compared with standard intensity RRT has survival benefit and
      achieves better renal recovery in acute kidney injury (AKI). Methods: In an
      individual patient data meta-analysis, we merged individual patient data from
      randomized controlled trials (RCTs) comparing high with standard intensity RRT in
      intensive care unit patients with severe AKI. The primary outcome was all-cause
      mortality. The secondary outcome was renal recovery assessed as the proportion of
      patients who were RRT dependent at key trial endpoints and by time to the end of
      RRT dependence. Results: Of the eight prospective RCTs assessing different RRT
      intensities, seven contributed individual patient data (n = 3682) to the
      analysis. Mortality was similar between the two groups at 28 days [769/1884
      (40.8%) and 744/1798 (41.4%), respectively; P = 0.40] after randomization.
      However, more participants assigned to higher intensity therapy remained RRT
      dependent at the most common key study point of 28 days [e.g. 292/983 (29.7%)
      versus 235/943 (24.9%); relative risk 1.15 (95% confidence interval 1.00-1.33); P
      = 0.05]. Time to cessation of RRT through 28 days was longer in patients
      receiving higher intensity RRT (log-rank test P = 0.02) and when continuous renal
      replacement therapy was used as the initial modality of RRT (log-rank test P =
      0.03). Conclusions: In severe AKI patients, higher intensity RRT does not affect
      mortality but appears to delay renal recovery. Trial Registration: Australian New
      Zealand Clinical Trials Registry (ANZCTR) identifier ACTRN12615000394549
      (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=126150003945
      9).

PMID- 29186516
TI  - Transgenic Bt Corn, Soil Insecticide, and Insecticidal Seed Treatment Effects on
      Corn Rootworm (Coleoptera: Chrysomelidae) Beetle Emergence, Larval Feeding
      Injury, and Corn Yield in North Dakota.
AB  - Northern, Diabrotica barberi Smith & Lawrence (Coleoptera: Chrysomelidae), and
      western, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), corn
      rootworms are economic pests of corn, Zea mays L. in North America. We measured
      the impacts of corn hybrids incorporated with Cry3Bb1, Cry34/35Ab1, and pyramided
      (Cry3Bb1 + Cry34/35Ab1) Bacillus thuringiensis Berliner (Bt) proteins, tefluthrin
      soil insecticide, and clothianidin insecticidal seed treatment on beetle
      emergence, larval feeding injury, and corn yield at five locations from 2013 to
      2015 in eastern North Dakota. In most cases, emergence was significantly lower in
      Bt-protected corn than in non-Bt corn hybrids. Exceptions included Wyndmere, ND
      (2013), where D. barberi emergence from Cry34/35Ab1 plots was not different from
      that in the non-Bt hybrid, and Arthur, ND (2013), where D. v. virgifera emergence
      from Cry3Bb1 plots did not differ from that in the non-Bt hybrid. Bt hybrids
      generally produced increased grain yield compared with non-Bt corn where rootworm
      densities were high, and larval root-feeding injury was consistently lower in Bt
      protected plots than in non-Bt corn. The lowest overall feeding injury and
      emergence levels occurred in plots planted with the Cry3Bb1 + Cry34/35Ab1 hybrid.
      Time to 50% cumulative emergence of both species was 5-7 d later in Bt-protected
      than in non-Bt hybrids. Tefluthrin and clothianidin were mostly inconsequential
      in relation to beetle emergence and larval root injury. Our findings could
      suggest that some North Dakota populations could be in early stages of increased
      tolerance to some Bt toxins; however, Bt corn hybrids currently provide effective
      protection against rootworm injury in eastern North Dakota.

PMID- 29186519
TI  - Effects of Fatty Acid and Geraniol Repellent-Oil Mixtures Applied to Cattle on
      Blood Feeding and Reproductive Parameters in Field Populations of Haematobia
      irritans (Diptera: Muscidae).
AB  - California pastured cattle were treated with 250 ml of a 15% mixture of fatty
      acids (C8-C9-C10) or 125 ml of 2% geraniol in a mineral oil carrier to assess
      impacts on horn flies, Haematobia irritans (L.) (Diptera: Muscidae) over two
      summers. Horn flies were netted from cattle every 3-4 d for 2 wk before
      treatment, 2 wk during treatment (four treatments, with flies collected before
      each treatment), and 2 wk after treatments ceased. Blood meal weights were
      estimated by hemoglobin assay of excised abdomens. Other females were dissected
      to determine the number of active ovarioles and the stage of primary follicle
      development. Depending on year and herd, pretreatment males contained an average
      of 0.6-1.0 mg of blood, while females contained 1.7-2.7 mg. Pretreatment egg
      development (least developed oocytes were stage 1 and fully developed eggs were
      stage 5) averaged 3.7-4.3, and number of active ovarioles averaged 18.1 to
      19.6/female. During treatment periods, significant reductions in blood weight
      were noted for females, but usually not for males, and females also often
      exhibited reduced mean oocyte stage and number of active ovarioles. Peaks in
      proportions of young nulliparous females (oocyte stages 1 or 2) were seen during
      some repellent application periods. This suggested older females had been killed
      or driven off from the local population by the treatments, and flies on cattle
      included more young flies that likely were recent arrivals. The repellent-oil
      mixture thus impacted blood feeding, reproductive fitness, and probably age
      structure in the field.

PMID- 29186520
TI  - Intrapuparial Development of Sarconesia Chlorogaster (Diptera: Calliphoridae) for
      Postmortem Interval Estimation (PMI).
AB  - Sarconesia chlorogaster (Wiedemann) (Diptera: Calliphoridae) is an endemic blow
      fly species of forensic importance in South America, and whose duration of pupal
      development is about 70% of the total immature development time. Therefore,
      morphological changes during this stage, if refined, may provide greater accuracy
      and reliability in the calculation of minimum postmortem interval. Considering
      the importance of this species, the main objective of this work was to identify
      and describe temporal intrapuparial morphological changes of S. chlorogaster. The
      development of S. chlorogaster reared on an artificial diet and at two constant
      temperatures (20 and 25oC) was monitored. Every 8 h until the end of the pupal
      stage, 10 pupae were killed, fixed, and had their external morphology described
      and photographed. Of the 29 morphological characteristics described, 13 are
      potentially informative for estimating the age of S. chlorogaster. In general,
      body shape (presence or absence of tagmatization), general coloration, visible
      presence of the mouth hook (portion of the mandible), thoracic appendages, change
      in eye color, and bristle formation are the most useful characteristics for
      determining specific age. The results presented here make it possible to estimate
      the postmortem interval of a corpse using intrapuparial morphological characters,
      expanding one's ability to estimate postmortem interval.

PMID- 29186518
TI  - Diversity-generating retroelements: natural variation, classification and
      evolution inferred from a large-scale genomic survey.
AB  - Diversity-generating retroelements (DGRs) are novel genetic elements that use
      reverse transcription to generate vast numbers of sequence variants in specific
      target genes. Here, we present a detailed comparative bioinformatic analysis that
      depicts the landscape of DGR sequences in nature as represented by data in
      GenBank. Over 350 unique DGRs are identified, which together form a curated
      reference set of putatively functional DGRs. We classify target genes, variable
      repeats and DGR cassette architectures, and identify two new accessory genes. The
      great variability of target genes implies roles of DGRs in many undiscovered
      biological processes. There is much evidence for horizontal transfers of DGRs,
      and we identify lineages of DGRs that appear to have specialized properties.
      Because GenBank contains data from only 10% of described species, the compilation
      may not be wholly representative of DGRs present in nature. Indeed, many DGR
      subtypes are present only once in the set and DGRs of the candidate phylum
      radiation bacteria, and Diapherotrites, Parvarchaeota, Aenigmarchaeota,
      Nanoarchaeota, Nanohaloarchaea archaea, are exceptionally diverse in sequence,
      with little information available about functions of their target genes.
      Nonetheless, this study provides a detailed framework for classifying and
      studying DGRs as they are uncovered and studied in the future.

PMID- 29186515
TI  - Assessment of moderate coffee consumption and risk of epithelial ovarian cancer:
      a Mendelian randomization study.
AB  - Background: Coffee consumption has been shown to be associated with various
      health outcomes in observational studies. However, evidence for its association
      with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether
      these associations are causal. Methods: We used single nucleotide polymorphisms
      associated with (i) coffee and (ii) caffeine consumption to perform Mendelian
      randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data
      on 44 062 individuals of European ancestry from the Ovarian Cancer Association
      Consortium (OCAC), and combined instrumental variable estimates using a Wald-type
      ratio estimator. Results: For all EOC cases, the causal odds ratio (COR) for
      genetically predicted consumption of one additional cup of coffee per day was
      0.92 [95% confidence interval (CI): 0.79, 1.06]. The COR was 0.90 (95% CI: 0.73,
      1.10) for high-grade serous EOC. The COR for genetically predicted consumption of
      an additional 80 mg caffeine was 1.01 (95% CI: 0.92, 1.11) for all EOC cases and
      0.90 (95% CI: 0.73, 1.10) for high-grade serous cases. Conclusions: We found no
      evidence indicative of a strong association between EOC risk and genetically
      predicted coffee or caffeine levels. However, our estimates were not
      statistically inconsistent with earlier observational studies and we were unable
      to rule out small protective associations.

PMID- 29186521
TI  - Oxidation of Selected Phenothiazine Drugs During Sample Preparation: Effects of
      Varying Extraction Conditions on the Extent of Oxidation.
AB  - Characterization of degradation products formed from selected phenothiazine drugs
      during standard solid-phase extraction (SPE) approaches is described. An
      analytical method for promethazine (PMZ), chlorpromazine (CPZ) and their
      respective N-desmethyl and sulfoxide metabolites in biological samples (bone
      tissue extract and blood) by ultra performance liquid chromatography-photodiode
      array detection, using mixed-mode SPE for basic drugs was developed. When ethyl
      acetate:isopropanol:ammonium hydroxide (80:17:3) was used as the elution solvent
      during method development, extraneous peaks were observed that were absent in the
      negative controls. Analysis of extracts of PMZ and CPZ individually showed
      extraneous peaks, including peaks with retention time and UV spectra suggesting
      the formation of the sulfoxide metabolites, amongst others. Analytes were then
      extracted individually and analyzed by ultra performance liquid chromatography
      quadrupole time-of-flight mass spectrometry. The results confirmed the oxidation
      of PMZ to its sulfoxide and N-oxide metabolites and oxidation of CPZ to its
      sulfoxide metabolite. Oxidation was also observed in analysis of whole blood, and
      thus was not specific to bone tissue extract. To determine if extraction with
      minimal oxidation was possible, extractions using SPE with a different elution
      solvent system (dichloromethane:isopropanol:ammonium hydroxide) and
      filtration/pass through extraction (FPTE) with and without evaporation were
      evaluated. The results demonstrated that the sample preparation method highly
      influenced the extent of oxidation. FPTE without an evaporation step was the only
      method that did not measurably induce analyte oxidation.

PMID- 29186522
TI  - Prevalence and patterns of cognitive impairment in adult hemodialysis patients:
      the COGNITIVE-HD study.
AB  - Background: Mounting evidence indicates an increased risk of cognitive impairment
      in adults with end-stage kidney disease on dialysis, but the extent and pattern
      of deficits across the spectrum of cognitive domains are uncertain. Methods: We
      conducted a cross-sectional study of 676 adult hemodialysis patients from 20
      centers in Italy, aiming to evaluate the prevalence and patterns of cognitive
      impairment across five domains of learning and memory, complex attention,
      executive function, language and perceptual-motor function. We assessed cognitive
      function using a neuropsychological battery of 10 tests and calculated test and
      domain z-scores using population norms (age or age/education). We defined
      cognitive impairment as a z-score  <= -1.5. Results: Participants' median age was
      70.9 years (range 21.6-94.1) and 262 (38.8%) were women. Proportions of
      impairment on each domain were as follows: perceptual-motor function 31.5%
      (150/476), language 41.2% (273/662), executive function 41.7% (281/674), learning
      and memory 42.2% (269/638), complex attention 48.8% (329/674). Among 474
      participants with data for all domains, only 28.9% (n  =  137) were not impaired
      on any domain, with 25.9% impaired on a single domain (n  =  123), 17.3% on two
      (n  =  82), 13.9% on three (n  =  66), 9.1% on four (n  =  43) and 4.9% (n  = 
      23) on all five. Across patients, patterns of impairment combinations were
      diverse. Conclusions: In conclusion, cognitive impairment is extremely common in
      hemodialysis patients, across numerous domains, and patients often experience
      multiple deficits simultaneously. Clinical care should be tailored to meet the
      needs of patients with different types of cognitive impairment and future
      research should focus on identifying risk factors for cognitive decline.

PMID- 29186523
TI  - DNA-based mutation assay GPMA (genome profiling-based mutation assay):
      reproducibility, parts-per-billion scale sensitivity, and introduction of a
      mammalian-cell-based approach.
AB  - Genome profiling-based mutation assay (GPMA) is, to date, the only DNA sequence
      based mutation assay that directly measures DNA alterations induced by mutagens.
      Here, the all-important congruence of mutagen assignment between DNA-based GPMA
      and the phenotype-based Ames test (the gold standard of mutagen assays) was
      confirmed qualitatively and semi-quantitatively by means of 94 chemical species
      (including previously examined 64). The high sensitivity (on the order of 10 ppb)
      and reproducibility of GPMA were also corroborated by the match between virtually
      independent experiments conducted in the distant past (10 years ago) and
      recently. Meanwhile, a standard experimental framework was established: the
      conditions of 100 parts per billion (ppb) concentration of a chemical and 15
      generation culture of Escherichia coli. Moreover, a mammalian cell line (NIH 3T3)
      was shown to be suitable as a tester organism for the GPMA approach. Preliminary
      experimental results suggested that this approach can provide a qualitatively
      equivalent and quantitatively different mutagen assay results relative to the
      bacteria-based GPMA (renamed as bGPMA). This finding confirmed the effectiveness
      of the GPMA approach and indicates that mGPMA is a promising way to detect
      mammalian-cell mutagens.

PMID- 29186524
TI  - Inhibition of DNA replication by an anti-PCNA aptamer/PCNA complex.
AB  - Proliferating cell nuclear antigen (PCNA) is a multifunctional protein present in
      the nuclei of eukaryotic cells that plays an important role as a component of the
      DNA replication machinery, as well as DNA repair systems. PCNA was recently
      proposed as a potential non-oncogenic target for anti-cancer therapy. In this
      study, using the Systematic Evolution of Ligands by EXponential enrichment
      (SELEX) method, we developed a short DNA aptamer that binds human PCNA. In the
      presence of PCNA, the anti-PCNA aptamer inhibited the activity of human DNA
      polymerase delta and epsilon at nM concentrations. Moreover, PCNA protected the
      anti-PCNA aptamer against the exonucleolytic activity of these DNA polymerases.
      Investigation of the mechanism of anti-PCNA aptamer-dependent inhibition of DNA
      replication revealed that the aptamer did not block formation, but was a
      component of PCNA/DNA polymerase delta or epsilon complexes. Additionally, the
      anti-PCNA aptamer competed with the primer-template DNA for binding to the
      PCNA/DNA polymerase delta or epsilon complex. Based on the observations, a model
      of anti-PCNA aptamer/PCNA complex-dependent inhibition of DNA replication was
      proposed.

PMID- 29186525
TI  - Hot lungs, bitter cherry: intravascular lymphoma.

PMID- 29186526
TI  - Addressing the Potential for Perioperative Relapse in Those Recovering from
      Opioid Use Disorder.

PMID- 29186527
TI  - Grimstone v Epsom and St Helier University Hospitals NHS Trust: (It's Not) Hip to
      Be Square.
AB  - In Montgomery v Lanarkshire Health Board [2015] UKSC 11 the Supreme Court
      redefined the standard of disclosure in informed consent to medical treatment,
      rejecting the application of the doctor-focused Bolam standard in favour of one
      focused on what was significant to patients. In Grimstone v Epsom and St Helier
      University Hospitals NHS Trust [2015] EWHC 3756 (QB), despite acknowledging a new
      standard now applied, McGowan J nevertheless used the Bolam test to determine
      liability for non-disclosure. This illustrates ongoing judicial deference to the
      medical profession and this case commentary explores that decision and its
      implications.

PMID- 29186528
TI  - Conformational dynamism for DNA interaction in the Salmonella RcsB response
      regulator.
AB  - The RcsCDB phosphorelay system controls an extremely large regulon in
      Enterobacteriaceae that involves processes such as biofilm formation, flagella
      production, synthesis of extracellular capsules and cell division. Therefore,
      fine-tuning of this system is essential for virulence in pathogenic
      microorganisms of this group. The final master effector of the RcsCDB system is
      the response regulator (RR) RcsB, which activates or represses multiple genes by
      binding to different promoter regions. This regulatory activity of RcsB can be
      done alone or in combination with additional transcriptional factors in
      phosphorylated or dephosphorylated states. The capacity of RcsB to interact with
      multiple promoters and partners, either dephosphorylated or phosphorylated,
      suggests an extremely conformational dynamism for this RR. To shed light on the
      activation mechanism of RcsB and its implication on promoter recognition, we
      solved the crystal structure of full-length RcsB from Salmonella enterica serovar
      Typhimurium in the presence and absence of a phosphomimetic molecule BeF3-. These
      two novel structures have guided an extensive site-directed mutagenesis study at
      the structural and functional level that confirms RcsB conformational plasticity
      and dynamism. Our data allowed us to propose a beta5-T switch mechanism where
      phosphorylation is coupled to alternative DNA binding ways and which highlights
      the conformational dynamism of RcsB to be so pleiotropic.

PMID- 29186529
TI  - Protection of the Human Gut Microbiome From Antibiotics.
AB  - Background: Antibiotics are life-saving drugs but severely affect the gut
      microbiome with short-term consequences including diarrhea and selection of
      antibiotic-resistant bacteria. Long-term links to allergy and obesity are also
      suggested. We devised a product, DAV132, and previously showed its ability to
      deliver a powerful adsorbent, activated charcoal, in the late ileum of human
      volunteers. Methods: We performed a randomized controlled trial in 28 human
      volunteers treated with a 5-day clinical regimen of the fluoroquinolone
      antibiotic moxifloxacin in 2 parallel groups, with or without DAV132
      coadministration. Two control goups of 8 volunteers each receiving DAV132 alone,
      or a nonactive substitute, were added. Results: The coadministration of DAV132
      decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels
      were unaffected. Shotgun quantitative metagenomics showed that the richness and
      composition of the intestinal microbiota were largely preserved in subjects co
      treated with DAV132 in addition to moxifloxacin. No adverse effect was observed.
      In addition, DAV132 efficiently adsorbed a wide range of clinically relevant
      antibiotics ex vivo. Conclusions: DAV132 was highly effective to protect the gut
      microbiome of moxifloxacin-treated healthy volunteers and may constitute a
      clinical breakthrough by preventing adverse health consequences of a wide range
      of antibiotic treatments. Clinical Trials Registration: NCT02176005.

PMID- 29186530
TI  - Stability of Synthetic Piperazines in Human Whole Blood.
AB  - While circumventing legislative controls, synthetic piperazines are encountered
      as "legal" alternatives to ecstasy. Unforeseeable challenges may delay
      quantitative analysis of these compounds in biological fluids. Enzymatic
      reactions, matrix interferences and limited knowledge of analyte stability
      further complicate interpretation of calculated concentrations. The objective of
      this study was to investigate the stability of synthetic piperazines in human
      blood under various storage conditions over time. All samples were prepared by
      spiking certified reference standards (Cayman Chemical, MI, U.S.A.) of eight
      synthetic piperazine into certified drug-free human whole blood (UTAK
      Laboratories, Inc., CA, U.S.A.) independently at 1000 ng/mL as well as mixtures
      containing all tested piperazines in this study. Samples were stored at room
      temperature (~20 degrees C), 4 degrees C and -20 degrees C for 1, 3, 6, 9 and 12
      months in dark sealed containers. Solid phase extraction (SPE) was performed
      using mixed-mode copolymeric cartridges (Clean Screen(r), UCT Inc., PA, U.S.A.).
      Analytes were assessed on their degrees of degradation using a Shimadzu Ultra
      Fast Liquid Chromatograph with SCIEX 4000 Q-Trap Electrospray Ionization Tandem
      Mass Spectrometer (UFLC-ESI-MS/MS) in positive ionization mode. Of the two
      categories, benzyl piperazines were more stable than phenyl piperazines under all
      storage conditions, in which 1-(4-methylbenzyl)-piperazine (MBZP) had more than
      70% (769-1,047 ng/mL) remaining after 12 months. 1-(4-methoxyphenyl)-piperazine
      (MeOPP) was not detected under room and refrigerated temperatures after 6 months
      and was the least stable. Matrix interferences and drug-drug interaction were
      observed. Storing samples at room temperature should be avoided due to
      detrimental impacts on stability of piperazine compounds. For backlog situations,
      case samples suspected to contain synthetic piperazines should be kept frozen or
      refrigerated even for time periods as short as 30 days for optimal result. Phenyl
      piperazines stored for more than 6 months showed analyte degradation and loss of
      parent compounds after extended storage regardless of storage conditions.

PMID- 29186531
TI  - A Novel NAC-Type Transcription Factor, NAC87, from Oilseed Rape Modulates
      Reactive Oxygen Species Accumulation and Cell Death.
AB  - Reactive oxygen species (ROS) are thought to play a dual role in plants by
      functioning as signaling molecules and toxic by-products of aerobic metabolism.
      The hypersensitive response (HR) is a typical feature of immune responses in
      plants and also a type of programmed cell death (PCD). How these two processes
      are regulated in oilseed rape (Brassica napus L.) at the transcriptional level
      remains largely unknown. In this study, we report that an oilseed rape (Brassica
      napus L.) NAM-ATAF-CUC (NAC)-type transcription factor NAC87 modulates ROS and
      cell death accompanied by typical changes at the morphological and cellular
      levels. The BnaNAC87 gene was induced by multiple stress and hormone treatments
      and was highly expressed in senescent leaves by quantitative reverse
      transcription-PCR (qRT-PCR). BnaNAC87 is located in nuclei and has
      transcriptional activation activity. Expression of BnaNAC87 promoted significant
      ROS production, cell death as well as death of protoplasts, as indicated by
      histological staining. In addition, putative downstream target genes of NAC87
      were identified through both qRT-PCR and dual luciferase reporter assays. We
      found that genes implicated in ROS generation (RbohB), cell death (VPE1a, ZEN1),
      leaf senescence (WRKY6, ZAT12) and defense (PR2, PR5 and HIN1) were significantly
      induced. Through an electrophoretic mobility shift assay (EMSA), we confirmed
      that BnaNAC87 directly binds to the NACRS-containing promoter fragments of ZEN1,
      ZAT12, HIN1 and PR5 genes. From these results, we conclude that oilseed rape
      NAC87 is a novel NAC transcription factor that acts as a positive regulator of
      ROS metabolism and cell death.

PMID- 29186533
TI  - Surgical treatment for isolated mitral valve endocarditis: a 16-year single
      centre experience.
AB  - OBJECTIVES: Despite progress in management, mitral valve endocarditis (MVE) is
      still a life-threatening disease. We report our experience in surgical treatment
      of infective isolated MVE. METHODS: A total of 140 operations in 128 patients for
      MVE performed between January 2000 and December 2015 were included in a
      retrospective study. There were 109 (78%) operations for native and 31 (22%)
      operations for prosthetic valve endocarditis. Preoperative and postoperative
      characteristics and mortality of patients were registered. Cox regression
      identified factors associated with mortality. Mean follow-up period was 68 months
      (range 1-168 months) and 100% complete. RESULTS: There were 13 deaths within 30
      days after the 140 operations (9%). Severe perioperative complications occurred
      in 59 (42%) operations. Overall cumulative survival was 73% +/- 4 at 5 years and
      62 +/- 5% at 10 years after the first operation. Age, diabetes, EuroSCORE II and
      perivalvular abscess were independent predictors for long-term mortality. Valve
      repair was performed in 76 (54%) operations and replacement in 64 (46%)
      operations. Thirty-day mortality for repair was 1%, and 5-year and 10-year
      cumulative survival was 86 +/- 4% and 77 +/- 6%, respectively. In the replacement
      group the 30-day mortality was 19% and cumulative survival at 5 years and 10
      years was 55 +/- 7% and 41 +/- 8%, respectively. Postoperative complications
      occurred in 21% and 67%, respectively, after operations for repair and
      replacement. Ten (8%) patients had 12 reoperations for recurrent endocarditis.
      CONCLUSIONS: MVE requiring surgical treatment is a challenging disease with high
      hospital mortality after valve replacement. Mitral valve repair can be performed
      in suitable endocarditis patients with excellent results. Age, diabetes and
      EuroSCORE were independently associated with mortality in a multivariable model.

PMID- 29186532
TI  - Loss of offspring Peg3 reduces neonatal ultrasonic vocalizations and increases
      maternal anxiety in wild-type mothers.
AB  - Depression and anxiety are the most common mental health conditions during
      pregnancy and can impair the normal development of mother-infant interactions.
      These adversities are associated with low birth weight and increased risk of
      behavioural disorders in children. We recently reported reduced expression of the
      imprinted gene PATERNALLY EXPRESSED GENE 3 (PEG3) in placenta of human infants
      born to depressed mothers. Expression of Peg3 in the brain has previously been
      linked maternal behaviour in rodents, at least in some studies, with mutant dams
      neglecting their pups. However, in our human study decreased expression was in
      the placenta derived from the fetus. Here, we examined maternal behaviour in
      response to reduced expression of Peg3 in the feto-placental unit. Prenatally we
      found novelty reactivity was altered in wild-type females carrying litters with a
      null mutation in Peg3. This behavioural alteration was short-lived and there were
      no significant differences the transcriptomes of either the maternal hypothalamus
      or hippocampus at E16.5. In contrast, while maternal gross maternal care was
      intact postnatally, the exposed dams were significantly slower to retrieve their
      pups and displayed a marked increase in anxiety. We also observed a significant
      reduction in the isolation-induced ultrasonic vocalizations (USVs) emitted by
      mutant pups separated from their mothers. USVs are a form of communication known
      to elicit maternal care suggesting Peg3 mutant pups drive the deficit in maternal
      behaviour. These data support the hypothesis that reduced placental PEG3 in human
      pregnancies occurs as a consequence of prenatal depression but leaves scope for
      feto-placental Peg3 dosage, during gestation, influencing aspects of maternal
      behaviour.

PMID- 29186534
TI  - Temperature and Tissue Type Impact Development of Lucilia cuprina (Diptera:
      Calliphoridae) in Sri Lanka.
AB  - Lucilia cuprina (Wiedemann; Diptera: Calliphoridae) is a facultative ecto
      parasitic fly, distributed throughout the temperate and subtropical regions of
      the world. This blow fly species is of medical, veterinary, and forensic
      importance due to it being used in maggot debridement therapy (MDT), a causative
      agent of myiasis, and a decomposer of vertebrate carrion. The current study
      examined the combined effects of temperature and tissue type on the development
      of L. cuprina. Specimens were reared on three tissue types; swine muscle, swine
      liver, and bovine muscle at 20 degrees C, 25 degrees C, 27 degrees C, and 38
      degrees C. The optimum condition for L. cuprina development was for immatures
      reared on bovine muscle (287.4 h) followed by those reared on swine muscle (288.0
      h) and swine liver (288.4 h) at 27 degrees C. The minimum temperature threshold
      of L. cuprina was deduced to be 14 degrees C. No significant differences in
      larval width and length over time were determined for the tissue type.

PMID- 29186535
TI  - Analysis of last statements prior to execution: methods, themes and future
      directions.
AB  - Worldwide, over 1000 people were executed in 2016 and over 3000 sentenced to
      death. Death row prisoners have high rates of mental illness, often combined with
      neurological impairment. Prolonged confinement has further negative effects on
      psychological function. There is a growing literature examining key themes and
      psychological constructs in death row prisoners immediately prior to execution.
      To date, this literature centres largely but not exclusively on last statements
      from death row in Texas, owing to ease of availability. The most common themes in
      last statements are love, spirituality and apology or regret. The most common
      psychological constructs are 'identification-egression' (e.g. attachment to a
      lost person or ideal, such as freedom), unbearable psychological pain and
      rejection-aggression. This is still a relatively new area of research and new
      techniques, such as computerised quantitative text analysis, are likely to
      complement rather than replace more traditional forms of thematic and textual
      analysis. For the future, it is essential that studies in this field continue to
      specify precisely, which last statements they use, so that overlap can be
      identified, and that more countries are studied (if possible). It would also be
      useful to expand the research frame to relate the content of last statements to
      additional variables relating to prisoners' offences, physical health, mental
      health, family structure and broader circumstances. Finally, ethical issues
      require continued consideration in this complex, fascinating, growing field.

PMID- 29186536
TI  - Comparison and Mechanism of the UV-Resistant Mosquitocidal Bt Mutant LLP29-M19.
AB  - Bacillus thuringiensis (Bt) is one of the most widely used and studied
      biopesticides. However, it is vulnerable to the influence of ultraviolet (UV)
      radiation, causing shorter persistence under field conditions. To obtain a high
      active and effective Bt new product, the main objective of this study is to
      obtain a highly UV-resistant Bt mutant from the mosquitocidal Bt LLP29 through UV
      exposure. After 19 rounds of UV exposure, a Bt mutant named LLP29-M19 was
      obtained, showing resistance to UV radiation for up to 67 min. The mosquitocidal
      fatality rate of LLP29-M19 was 95%, which was slightly higher than that of LLP29
      (90%). Comparative characterization showed that there were no substantial
      differences in morphology between LLP29-M19 and the original strain, LLP29.
      However, some changes were detected in physiological and biochemical
      characteristic reactions, including fructose, glucose, and xylose metabolism.
      Furthermore, although both LLP29-M19 and LLP29 showed negative zeta potentials,
      the surface charge of LLP29 was -28.1 mV and that of LLP29-M19 was -42.8 mV. The
      size distribution of LLP29-M19 was also slightly larger than that of LLP29.
      Fourier transform infrared analysis indicated that amide functional groups might
      be involved in the resistance mechanism of LLP29-M19. Quantitative analysis using
      inductive coupled plasma emission spectrometry showed that some elements
      increased greatly in LLP29-M19, such as K. All of these results will be highly
      valuable for better understanding the mechanism of Bt resistance. Explanations
      regarding the resistance mechanism of this novel Bt mutant may lead to the
      development of new biopesticides with high mosquitocidal activity and
      persistence.

PMID- 29186537
TI  - Fabry disease under enzyme replacement therapy-new insights in efficacy of
      different dosages.
AB  - Background: Fabry patients on reduced dose of agalsidase-beta or after switch to
      agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and
      an increase of the Mainz Severity Score Index. Methods: In this prospective
      observational study, we assessed end-organ damage and clinical symptoms in 112
      patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i)
      non-randomly assigned to continue this treatment regime (regular-dose group, n =
      37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to
      agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa
      (switch group, n = 38); or (iii) were re-switched to agalsidase-beta after
      receiving agalsidase-alfa for at least 12 months (re-switch group, n = 37) with a
      median follow-up of 53 (38-57) months. Results: eGFR of patients in the regular
      dose group remained stable. Patients in the switch group showed an annual eGFR
      loss of - 4.6  +/-  9.1 mL/min/1.73 m2 (P < 0.05). Patients in the re-switch
      group also had an eGFR loss of - 2.2  +/-  4.4 mL/min/1.73 m2 after re-switch to
      agalsidase-beta, but to a lower degree compared with the switch group (P < 0.05).
      Patients in the re-switch group suffered less frequently from diarrhoea (relative
      risk 0.42; 95% confidence interval 0.19-0.93; P = 0.02). Lyso-Gb3 remained stable
      in the switch (P = 0.97) and the regular-dose (P = 0.48) groups, but decreased in
      the re-switch group after change of the therapy regimen (P < 0.05). Conclusions:
      After switch to agalsidase-alfa, Fabry patients experienced a continuous decline
      in eGFR, while this decline was attenuated in patients who were re-switched to
      agalsidase-beta. Decreasing lyso-Gb3 levels may indicate a better treatment
      response in the latter group.

PMID- 29186538
TI  - The potential for dual pathology in temporal arteritis.

PMID- 29186539
TI  - Reconstitution of the CstF complex unveils a regulatory role for CstF-50 in
      recognition of 3'-end processing signals.
AB  - Cleavage stimulation factor (CstF) is a highly conserved protein complex composed
      of three subunits that recognizes G/U-rich sequences downstream of the
      polyadenylation signal of eukaryotic mRNAs. While CstF has been identified over
      25 years ago, the architecture and contribution of each subunit to RNA
      recognition have not been fully understood. In this study, we provide a
      structural basis for the recruitment of CstF-50 to CstF via interaction with CstF
      77 and establish that the hexameric assembly of CstF creates a high affinity
      platform to target various G/U-rich sequences. We further demonstrate that CstF
      77 boosts the affinity of the CstF-64 RRM to the RNA targets and CstF-50 fine
      tunes the ability of the complex to recognize G/U sequences of certain lengths
      and content.

PMID- 29186540
TI  - An Underdiagnosed Cause of Anterior Lateral Hip Pain: Ultrasound Imaging and
      Guided Injection for Rectus Femoris Indirect Tendon Strain.

PMID- 29186542
TI  - Corrigendum.

PMID- 29186543
TI  - Field Evaluation of Commercial Attractants and Trap Placement for Monitoring Pine
      Sawyer Beetle, Monochamus alternatus (Coleoptera: Cerambycidae) in Guangdong,
      China.
AB  - The pine sawyer beetle, Monochamus alternatus Hope (Coleoptera: Cerambycidae) is
      a serious insect pest of pine trees by vectoring the pine wood nematode,
      Bursaphelenchus xylophilus (Steiner and Buhrer) Nickle (Nematoda:
      Aphelenchoididae). Field studies were carried out during 2013-2015 in Guangdong
      (China) to evaluate the effectiveness of commercial attractants, effect of trap
      placement for monitoring M. alternatus, and temporal patterns of trap catch. Four
      commercial attractants, three trap placements (0, 1.5, and 3 m above ground) and
      different trapping distances (50, 200, 400, 600, and 900 m) from forest edge were
      evaluated for monitoring M. alternatus. Traps baited with a mixture of monochamol
      and plant volatiles captured significantly more beetles than traps baited with
      monochamol alone or plant volatiles alone. Traps set up at 1.5 m above the ground
      captured significantly more M. alternatus than those at 0 m and 3 m height. Based
      on 2,687 beetles trapped from two locations in 2013 and 2014, the female:male
      ratio was 2.9-4.1:1. The beetles' natural dispersal distance was approximately
      100 m based on traps set at different distances from edge of the forest.
      Continuous monitoring over 38-wk period indicates the peak of adult M. alternatus
      emergence was between May and June within a year.

PMID- 29186541
TI  - Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid
      arthritis.
AB  - RA is a chronic, systemic, autoimmune disease characterized by inflammation and
      degradation of the joints, causing significant negative impact on quality of
      life. In addition to joint disease, symptoms and co-morbidities associated with
      RA-namely pain, fatigue and mood disorders-are often as debilitating as the
      disease itself. The pro-inflammatory cytokine IL-6 plays a critical role in RA
      associated pathology. However, a greater understanding of the translational
      effects of IL-6 outside of the immune system is needed. This review discusses our
      current understanding of emerging aspects of IL-6 in RA-associated pain, fatigue
      and mood disorders such as depression and anxiety. This review also describes the
      clinical effects of IL-6 inhibition on these symptoms and co-morbidities in
      patients with RA.

PMID- 29186544
TI  - Characterizing environmental suitability of Aedes albopictus (Diptera: Culicidae)
      in Mexico based on regional and global niche models.
AB  - The Asian tiger mosquito, Aedes albopictus (Skuse) (Diptera: Culicidae), is an
      invasive species and a vector of numerous human pathogens, including chikungunya,
      dengue, yellow fever, and Zika viruses. This mosquito had been reported from 36
      geographic locations in Mexico by 2005, increasing to 101 locations by 2010 and
      501 locations (spanning 16 states) by 2016. Here we modeled the occupied niche
      for Ae. albopictus in Mexico to characterize the environmental conditions related
      to its presence, and to generate updated environmental suitability maps. The
      predictors with the greatest contribution to characterizing the occupied niche
      for Ae. albopictus were NDVI and annual mean temperature. We also estimated the
      environmental suitability for Ae. albopictus in regions of the country where it
      has not been documented yet, by means of: 1) transferring its occupied niche
      model to these regions and 2) modeling its fundamental niche using global data.
      Our models will help vector control and public health institutions to identify
      areas where Ae. albopictus has not yet been recorded but where it may be present.
      We emphasize that most of Mexico has environmental conditions that potentially
      allow the survival of Ae. albopictus, which underscores the need for systematic
      mosquito monitoring in all states of the country.

PMID- 29186545
TI  - PaSD-qc: quality control for single cell whole-genome sequencing data using power
      spectral density estimation.
AB  - Single cell whole-genome sequencing (scWGS) is providing novel insights into the
      nature of genetic heterogeneity in normal and diseased cells. However, the whole
      genome amplification process required for scWGS introduces biases into the
      resulting sequencing that can confound downstream analysis. Here, we present a
      statistical method, with an accompanying package PaSD-qc (Power Spectral Density
      qc), that evaluates the properties and quality of single cell libraries. It uses
      a modified power spectral density to assess amplification uniformity, amplicon
      size distribution, autocovariance and inter-sample consistency as well as to
      identify chromosomes with aberrant read-density profiles due either to copy
      alterations or poor amplification. These metrics provide a standard way to
      compare the quality of single cell samples as well as yield information necessary
      to improve variant calling strategies. We demonstrate the usefulness of this tool
      in comparing the properties of scWGS protocols, identifying potential chromosomal
      copy number variation, determining chromosomal and subchromosomal regions of poor
      amplification, and selecting high-quality libraries from low-coverage data for
      deep sequencing. The software is available free and open-source at
      https://github.com/parklab/PaSDqc.

PMID- 29186546
TI  - Automated lipid-rich plaque detection with short wavelength infra-red OCT system.
AB  - Aims: Vulnerable coronary plaque is characterized by a large lipid core. Although
      commercially-available optical coherence tomography (OCT) systems use near
      infrared light at 1300 nm wavelength, lipid shows characteristic absorption at
      1700 nm. Therefore, we developed a novel, short wavelength infra-red,
      spectroscopic, spectral-domain OCT. The aim of the present study is to evaluate
      the accuracy of short wavelength (1700 nm) infra-red optical coherence tomography
      (SWIR-OCT) for identification of lipid tissue within coronary plaques. Methods
      and results: Twenty-three coronary arteries from 10 cadavers were imaged at
      physiological pressure with 2.7 Fr SWIR-OCT catheter. When a blood-free image was
      observed, the SWIR-OCT imaging core was withdrawn at a rate of 20 mm/s using an
      automatic pullback device. SWIR-OCT images were acquired at 94 frames/s and
      digitally archived. SWIR-OCT generated grey-scale cross sectional images and
      colour tissue maps of all of the plaque by using a lipid analysis algorithm.
      After SWIR-OCT imaging, the arteries were pressure-fixed, sliced by cryostat and
      stained with Oil Red O, and then corresponding histology was collected in matched
      images. Regions of interest, selected from histology, were 117 lipidic and 34
      fibrotic/calcified regions. SWIR-OCT showed high sensitivity (89%) and
      specificity (92%) for identifying lipid tissue within coronary plaques. The
      positive predictive value and negative predictive value were 97% and 74%,
      respectively. Conclusion: SWIR-OCT accurately identified lipid tissue in coronary
      autopsy specimens. This new technique may hold promise for identifying
      histopathological features of coronary plaque at risk for rupture.

PMID- 29186547
TI  - Koilonychia in iron deficiency.

PMID- 29186548
TI  - Neuromodulation Device Comparison Studies Come of Age.

PMID- 29186549
TI  - Intradialytic hypertension is associated with low intradialytic arterial oxygen
      saturation.
AB  - Background: The pathophysiology of a paradoxical systolic blood pressure (SBP)
      rise during hemodialysis (HD) is not yet fully understood. Recent research
      indicated that 10% of chronic HD patients suffer from prolonged intradialytic
      hypoxemia. Since hypoxemia induces a sympathetic response we entertained the
      hypothesis that peridialytic SBP change is associated with arterial oxygen
      saturation (SaO2). Methods: We retrospectively analyzed intradialytic SaO2 and
      peridialytic SBP change in chronic HD patients with arteriovenous vascular
      access. Patients were followed for 6 months. We defined persistent intradialytic
      hypertension (piHTN) as average peridialytic SBP increase >=10 mmHg over 6
      months. Linear mixed effects (LME) models were used to explore associations
      between peridialytic SBP change and intradialytic SaO2 in univariate and adjusted
      analyses. Results: We assessed 982 patients (29 872 HD treatments; 59% males; 53%
      whites). Pre-dialysis SBP was 146.7 +/- 26.5 mmHg and decreased on average by
      10.1 +/- 24.5 mmHg. Fifty-three (5.7%) patients had piHTN. piHTN patients had
      lower intradialytic SaO2, body weight and interdialytic weight gain. LME models
      revealed that with every percentage point lower mean SaO2, the peridialytic SBP
      change increased by 0.46 mmHg (P < 0.001). This finding was corroborated in
      multivariate analyses. Conclusion: We observed an inverse relationship between
      intradialytic SaO2 and the blood pressure response to HD. These findings support
      the notion that hypoxemia activates mechanisms that partially blunt the
      intradialytic blood pressure decline, possibly by sympathetic activation and
      endothelin-1 secretion. To further explore that hypothesis, specifically designed
      prospective studies are required.

PMID- 29186551
TI  - The Johns Hopkins Atlas of Surgical Neuropathology (iPad Application).

PMID- 29186550
TI  - An objective neural signature of rapid perspective taking.
AB  - The frequency-tagging approach has generally been confined to study low-level
      sensory processes and always found related activation over the occipital region.
      Here for the first time, we investigated with it, high-level socio-cognitive
      functions, i.e. the processing of what other people are looking at which is
      referred to as level 1 visual perspective taking (VPT). Sixteen participants were
      presented with visual scenes alternating at 2.5 Hz which were depicting a person
      and an object in a room, while recording electrophysiological brain activity. The
      person orientation and object position changed at every stimulus but the person
      in the room always faced the object, except on every fifth stimulus. We found
      responses in the electroencephalography (EEG) spectrum exactly at the frequency
      corresponding to the presentation of the scenes where the person could not see
      the object, i.e. 0.5 Hz. While the 2.5 Hz stimulation rate response focused on
      typical medial occipital sites, the specific 0.5 Hz response was found mainly
      over a centro-parietal region. Besides a robust group effect, these responses
      were significant and quantifiable for most individual participants. Overall,
      these observations reveal a clear measure of level 1-VPT representation,
      highlighting the potential of EEG frequency-tagging to capture high-level socio
      cognitive functions in the brain.

PMID- 29186553
TI  - Corrigendum to: "Probabilistic Distances Between Trees".

PMID- 29186552
TI  - Regulation of the epithelial barrier by post-translational modifications of tight
      junction membrane proteins.
AB  - Body and organ surfaces in multicellular organisms are covered with a sheet of
      epithelial cells. The tight junction (TJ) is an adhesive structure that seals the
      gap between epithelial cells and functions as a selective barrier to prevent the
      entry of antigens and pathogenic microbes from the extracellular environment.
      Several transmembrane proteins that constitute the TJ (claudin, occludin,
      tricellulin and angulin) have been identified. As over-expression of these
      proteins does not enlarge TJs or enhance epithelial barrier function, it remains
      unclear how TJ membrane proteins are regulated to modulate the amount of TJ and
      the strength of the epithelial barrier. In this review, we discuss the post
      translational modifications of TJ membrane proteins and their physiological
      significance from the viewpoint of the dynamic regulation of the epithelial
      barrier.

PMID- 29186554
TI  - Preclinical validation of a targeted next generation sequencing-based
      comprehensive chromosome screening methodology in human blastocysts.
AB  - STUDY QUESTION: Can a novel targeted next generation sequencing (tNGS) platform
      accurately detect whole chromosome aneuploidy in a trophectoderm biopsy and
      provide additional information to improve testing? SUMMARY ANSWER: Karyotypes
      obtained by tNGS were concordant with other validated platforms and single
      nucleotide polymorphism genotyping information obtained can be used for improved
      detection and quality control. WHAT IS KNOWN ALREADY: qPCR-based whole chromosome
      aneuploidy screening is highly accurate in comparison to other common methods and
      has been shown to improve IVF success in two randomized clinical trials. With
      aneuploidy screening becoming standard of care in many IVF centres, there is a
      need to develop platforms with high throughput, low cost capabilities. STUDY
      DESIGN SIZE, DURATION: Twelve well-characterized cell lines were obtained from a
      commercial cell line repository and 31 discarded human blastocysts were obtained
      from 17 IVF patients who underwent comprehensive chromosome screening (CCS).
      PARTICIPANTS/MATERIAL, SETTING, METHODS: All samples were processed using a
      unique amplification strategy which directly incorporated sequencing library
      adapters and barcodes. Sequencing was performed on an Ion Torrent Proton. A
      custom bioinformatics pipeline was used to determine the karyotype for each
      sample. The consistency of tNGS diagnoses with either conventional karyotyping of
      cell lines or quantitative real-time PCR based CCS of blastocyst biopsies was
      evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Overall consistency per sample of
      tNGS based CCS in 5-cell samples from a variety of cell lines was 99.2%. In the
      blinded analysis of rebiopsies of aneuploid blastocysts, an overall targeted tNGS
      CCS consistency of 98.7% was observed per sample. These data demonstrate the
      ability of tNGS based CCS to provide an accurate and high throughput evaluation
      of aneuploidy in the human blastocyst. LARGE SCALE DATA: Not applicable.
      LIMITATIONS REASONS FOR CAUTION: This study is limited to whole chromosome
      aneuploidy, as mosaicism and segmental aneuploidy have not been investigated.
      WIDER IMPLICATIONS OF THE FINDINGS: These data show an accurate, high throughput
      method, and with the greater depth of each amplicon sequenced in comparison to
      commercial kits, there is greater application available for single nucleotide
      polymorphism based analysis for quality control. STUDY FUNDING/COMPETING
      INTERESTS: This study was funded through intramural research funds provided by
      the Foundation for Embryonic Competence. There are no competing interests.

PMID- 29186555
TI  - Positive Self-perceptions of Aging Promote Healthy Eating Behavior Across the
      Life Span via Social-Cognitive Processes.
AB  - Objectives: Negative self-perceptions of aging (SPA) have been shown to result in
      lower levels of preventive behavior, health, and longevity. This study focuses on
      the understudied SPA effects on healthy eating across the life span. Moreover, it
      aims to provide longitudinal evidence of the psychological mechanisms behind this
      relationship. Method: We investigated whether SPA (T1) can predict changes in
      eating behavior (T3) over 1 year in 1,321 participants (T1), aged 18-92 years.
      The explanatory role of social-cognitive processes (T1, T2) was tested via a two
      step mediation analysis with multigroup modeling for different age and education
      levels. Results: Baseline positive SPA predicted more healthy eating at T3 (b =
      0.68, SE = 0.24, p = .01), controlling for baseline eating (T1), age, education,
      gender, BMI, and illnesses. Self-efficacy (T1) and intention to eat healthily
      (T2) serially mediated this effect, indirect effect: b = 0.04, p = .02, 95% CI
      (0.02, 0.08). SPA had stronger effects in older and less educated participants.
      Discussion: This study provides important insights into the mechanisms behind
      positive SPA fueling successful health behavior change dynamics. Fostering more
      positive SPA through interventions might be especially important for vulnerable
      groups. Addressing SPA already in younger ages might help establish health
      promoting life-span dynamics.

PMID- 29186556
TI  - Idiopathic mesenteric phlebosclerosis.

PMID- 29186557
TI  - Analgesic-Related Medication Errors Reported to US Poison Control Centers.
AB  - Objective: This study investigates the characteristics and trends of medication
      errors involving analgesic medications. Design and Methods: A retrospective
      analysis was conducted of analgesic-related medication errors reported to the
      National Poison Data System (NPDS) from 2000 through 2012. Results: From 2000
      through 2012, the NPDS received 533,763 reports of analgesic-related medication
      errors, averaging 41,059 medication errors annually. Overall, the rate of
      analgesic-related medication errors reported to the NPDS increased significantly
      by 82.6% from 2000 to 2009, followed by a 5.7% nonsignificant decrease from 2009
      to 2012. Among the analgesic categories, rates of both acetaminophen-related and
      opioid-related medication errors reported to the NPDS increased during 2000-2009,
      but the opioid error rate leveled off during 2009-2012, while the acetaminophen
      error rate decreased by 17.9%. Analgesic-related medication errors involved
      nonsteroidal anti-inflammatory drugs (37.0%), acetaminophen (35.5%), and opioids
      (23.2%). Children five years or younger accounted for 38.8% of analgesics-related
      medication errors. Most (90.2%) analgesic-related medication errors were managed
      on-site, rather than at a health care facility; 1.6% were admitted to a hospital,
      and 1.5% experienced serious medical outcomes, including 145 deaths. The most
      common type of medication error was inadvertently taking/given the medication
      twice (26.6%). Conclusions: Analgesic-related medication errors are common, and
      although most do not result in clinical consequences, they can have serious
      adverse outcomes. Initiatives associated with the decrease in acetaminophen
      related medication errors among young children merit additional research and
      potential replication as a model combining government policy and multisectoral
      collaboration.

PMID- 29186558
TI  - Essential role for phytol kinase and tocopherol in tolerance to combined light
      and temperature stress in tomato.
AB  - In a changing environment, plants need to cope with the impact of rising
      temperatures together with high light intensity. Here, we used lipidomics in the
      tomato model system to identify lipophilic molecules that enhance tolerance to
      combined high-temperature and high-light stress. Among several hundred
      metabolites, the two most strongly up-regulated compounds were alpha-tocopherol
      and plastoquinone/plastoquinol. Both are well-known lipid antioxidants and
      contribute to the protection of photosystem II (PSII) against photodamage under
      environmental stress. To address the protective function of tocopherol, an RNAi
      line (vte5) with decreased expression of VTE5 and reduced levels of alpha
      tocopherol was selected. VTE5 encodes phytol kinase, which acts in the
      biosynthetic pathway of tocopherols. vte5 suffered strong photoinhibition and
      photobleaching when exposed to combined high-light and high-temperature stress,
      but neither stress alone produced a visible phenotype. As vte5 had plastoquinone
      levels similar to those of the wild type under combined stress, the strong
      phenotype could be attributed to the lack of alpha-tocopherol. These findings
      suggest that VTE5 protects against combined high-light and high-temperature
      stress and does so by supporting alpha-tocopherol production.

PMID- 29186559
TI  - PHYLOSCANNER: Inferring Transmission from Within- and Between-Host Pathogen
      Genetic Diversity.
AB  - A central feature of pathogen genomics is that different infectious particles
      (virions, bacterial cells, etc.) within an infected individual may be genetically
      distinct, with patterns of relatedness amongst infectious particles being the
      result of both within-host evolution and transmission from one host to the next.
      Here we present a new software tool, phyloscanner, which analyses pathogen
      diversity from multiple infected hosts. phyloscanner provides unprecedented
      resolution into the transmission process, allowing inference of the direction of
      transmission from sequence data alone. Multiply infected individuals are also
      identified, as they harbour subpopulations of infectious particles that are not
      connected by within-host evolution, except where recombinant types emerge. Low
      level contamination is flagged and removed. We illustrate phyloscanner on both
      viral and bacterial pathogens, namely HIV-1 sequenced on Illumina and Roche 454
      platforms, HCV sequenced with the Oxford Nanopore MinION platform, and
      Streptococcus pneumoniae with sequences from multiple colonies per individual.
      phyloscanner is available from https://github.com/BDI-pathogens/phyloscanner.

PMID- 29186561
TI  - Identification of 5-Fluoro ADB in Human Whole Blood in Four Death Cases.
AB  - Four deaths that seemed to have been caused by a designer drug occurred within a
      3-week period in Sendai, Japan. In each case, the decedent possessed the same
      sachet, labeled "Heart Shot BLACK", which contained a dried plant material with
      an aromatic scent. It was revealed in our analysis that the product contained a
      synthetic cannabinoid receptor agonist, 5-fluoro ADB (methyl 2-[1-(5
      fluoropentyl)-1H-indazole-3-carboxamide]-3,3-dimethylbutanoate, also known as 5
      fluoro MDMB-PINACA), which is now classified as a restricted designer drug in
      Japan after it caused several casualties. For standard samples, the detection of
      5-fluoro ADB in whole blood in the calibration range (0.04-4 ng/mL) was
      successful with recoveries of 94.6-98.1%, limits of detection of 6 pg/mL, and
      limits of quantification of 40 pg/mL. The intraday and interday precisions were
      0.9-4.8% and 1.1-6.6%, respectively. The bias was -1.1 to 2.9%. We were able to
      confirm that 5-fluoro ADB was present in the blood of all four decedents at a
      concentration of 0.11-1.92 ng/mL. From the autopsy, toxicological findings, and
      circumstances surrounding the cases, it was considered that inhalation of 5
      fluoro ADB could have contributed to the deaths. However, the extent to which 5
      fluoro ADB contributed to the deaths remains unclear due to the current lack of
      toxicological information on the compound. In future research, the toxicity of 5
      fluoro ADB in humans and the mechanism underlying this effect need to be
      elucidated.

PMID- 29186560
TI  - The Intracellular Localization of the Vanillin Biosynthetic Machinery in Pods of
      Vanilla planifolia.
AB  - Vanillin is the most important flavor compound in the vanilla pod. Vanilla
      planifolia vanillin synthase (VpVAN) catalyzes the conversion of ferulic acid and
      ferulic acid glucoside into vanillin and vanillin glucoside, respectively.
      Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) of
      vanilla pod sections demonstrates that vanillin glucoside is preferentially
      localized within the mesocarp and placental laminae whereas vanillin is
      preferentially localized within the mesocarp. VpVAN is present as the mature form
      (25 kDa) but, depending on the tissue and isolation procedure, small amounts of
      the immature unprocessed form (40 kDa) and putative oligomers (50, 75 and 100
      kDa) may be observed by immunoblotting using an antibody specific to the C
      terminal sequence of VpVAN. The VpVAN protein is localized within chloroplasts
      and re-differentiated chloroplasts termed phenyloplasts, as monitored during the
      process of pod development. Isolated chloroplasts were shown to convert
      [14C]phenylalanine and [14C]cinnamic acid into [14C]vanillin glucoside,
      indicating that the entire vanillin de novo biosynthetic machinery converting
      phenylalanine to vanillin glucoside is present in the chloroplast.

PMID- 29186562
TI  - Adaptation of an Evidence-Based Diabetes Management Intervention for Delivery in
      Community Settings: Findings From a Pilot Randomized Effectiveness Trial.
AB  - Objective: To adapt an evidence-based intervention targeting diabetes management
      in adolescents with poorly controlled type 1 diabetes for use in a community
      setting by community health workers (CHWs) and to conduct pilot testing of the
      new intervention, REACH for Control (RFC). The study was conducted as a
      collaboration between university researchers and a federally qualified health
      center. Methods: In a pilot effectiveness trial, feasibility and acceptability of
      RFC were evaluated based on participant enrollment, treatment dose, and consumer
      satisfaction. RFC effects on adolescent adherence, health outcomes, and quality
      of life were also assessed. The trial used a parallel group design. Families were
      randomized to 6 months of RFC plus standard medical care (n = 26) or standard
      care (SC) only (n = 24). Data were collected at baseline and 7-month posttest. A
      mixed-methods approach was used to analyze data. Results: Qualitative analyses
      suggested that caregivers viewed RFC and delivery of a home-based intervention by
      CHWs positively. Furthermore, adolescents who received RFC had statistically
      significant (p = .05) and clinically meaningful improvements in hemoglobin A1c
      (HbA1c) (0.7%) and reported significant improvements in quality of life from
      baseline to follow-up (p = .001). No significant changes were found for
      adolescents in standard medical care. However, while dose of primary intervention
      session delivered was acceptable, dose of follow-up sessions used for skills
      practice was low. Conclusions: Results provide preliminary support for RFC's
      acceptability and effectiveness to improve health status and quality of life when
      used in community settings serving high-risk, low-income families. Additional
      testing in a full-scale effectiveness trial appears warranted.

PMID- 29186564
TI  - Erratum to: Sala L, et al. Action potential contour contributes to species
      differences in repolarization response to beta-adrenergic stimulation.

PMID- 29186563
TI  - Congenital absence of inferior vena cava: an under recognised cause of unprovoked
      venous thromboembolism.

PMID- 29186565
TI  - Computed tomography-based image-guided brachytherapy for cervical cancer:
      correlations between dose-volume parameters and clinical outcomes.
AB  - This study evaluated the oncologic outcomes and complications of cervical cancer
      patients in terms of CT-based image-guided brachytherapy (IGBT) parameters. Of 68
      cervical cancer patients treated with definitive radiotherapy/concurrent
      chemoradiotherapy, most received whole-pelvis external beam RT (EBRT) of 40 Gy in
      20 fractions, pelvic EBRT with central shield of 10 Gy in 5 fractions, and CT
      based IGBT of 18 Gy in 3 fractions prescribed to point A. Cumulative EBRT and
      IGBT doses were calculated as the total equivalent dose in 2 Gy fractions (EQD2).
      The median follow-up was 31 (3-52) months. The 2-year overall survival, local
      control, pelvic control, and disease-free survival rates of the 68 patients were
      92%, 83%, 82% and 73%, respectively. The HR-CTV D90, length from the tandem axis
      to left/right margin of the HR-CTV (T-LR), and HR-CTV volume were significant
      IGBT parameters for predicting local/pelvic control. Patients who received an HR
      CTV D90 of >60 Gy, compared with <=60 Gy, had significantly better local/pelvic
      control. Furthermore, 70 Gy was a marginally significant HR-CTV D90 cut-off
      affecting local control. T-LR was an independent IGBT parameter predicting
      local/pelvic control on multivariate analysis. Three patients developed Grade 3
      or higher treatment-related complications. The D2cm3 of organs at risk were not
      significant predictors of complications. Future challenges for further improving
      outcomes include additional interstitial needles for irregularly shaped HR-CTVs,
      and moderate dose escalation, especially for patients with poor tumor responses.

PMID- 29186566
TI  - Long-Term Perspectives of Family Quality of Life Following Music Therapy With
      Young Children on the Autism Spectrum: A Phenomenological Study.
AB  - Background: Parents of children on the autism spectrum have consistently reported
      feeling uncertain in their parenting role, and desire more practical advice from
      service providers about how to support their child in the home. There is growing
      recognition of the need for interventions to provide support to the family as
      well as fostering child development outcomes. Objective: This study explores
      mothers' follow-up perspectives of family-centered music therapy (FCMT) four
      years after participating in a 16-week home-based program, and therefore provides
      a unique long-term viewpoint on FCMT outcomes. Methods: Eight mothers who
      previously participated in FCMT sessions with their young children on the autism
      spectrum were interviewed to explore their perception of any long-term outcomes.
      Results: A descriptive phenomenological analysis revealed five global themes,
      including: improvement in mothers' confidence to engage their child; rare
      opportunities for mutual mother-child enjoyment; improved child social
      communication and quality of life; mothers' new understanding of the child's
      interests and strengths; and more opportunities for continuing the child's
      interest in music. Conclusions: Mothers perceived long-term benefits to social
      relationships within the family, leading to perceived enrichment in child and
      family quality of life following music therapy sessions.

PMID- 29186567
TI  - Dynamic m6A modification regulates local translation of mRNA in axons.
AB  - N6-methyladenosine (m6A) is a reversible modification in mRNA and has been shown
      to regulate processing, translation and decay of mRNA. However, the roles of m6A
      modification in neuronal development are still not known. Here, we found that the
      m6A eraser FTO is enriched in axons and can be locally translated. Axon-specific
      inhibition of FTO by rhein, or compartmentalized siRNA knockdown of Fto in axons
      led to increases of m6A levels. GAP-43 mRNA is modified by m6A and is a substrate
      of FTO in axons. Loss-of-function of this non-nuclear pool of FTO resulted in
      increased m6A modification and decreased local translation of axonal GAP-43 mRNA,
      which eventually repressed axon elongation. Mutation of a predicted m6A site in
      GAP-43 mRNA eliminated its m6A modification and exempted regulation of its local
      translation by axonal FTO. This work showed an example of dynamic internal m6A
      demethylation of non-nuclear localized mRNA by the demethylase FTO. Regulation of
      m6A modification of axonal mRNA by axonal FTO might be a general mechanism to
      control their local translation in neuronal development.

PMID- 29186568
TI  - Germline SUFU mutation carriers and medulloblastoma: clinical characteristics,
      cancer risk, and prognosis.
AB  - Background: Germline mutations of suppressor of fused homolog (SUFU) predispose
      to sonic hedgehog (SHH) medulloblastoma. Germline SUFU mutations have been
      reported in nevoid basal cell carcinoma syndrome (NBCCS), but little is known
      about the cancer risk and clinical spectrum. Methods: We performed a
      retrospective review of all patients with medulloblastoma and a germline SUFU
      mutation in France. Results: Twenty-two patients from 17 families were identified
      with medulloblastoma and a germline SUFU mutation (median age at diagnosis: 16.5
      mo). Macrocrania was present in 20 patients, but only 5 met the diagnostic
      criteria for NBCCS. Despite treatment with surgery and chemotherapy, to avoid
      radiotherapy in all patients except one, the outcome was worse than expected for
      SHH medulloblastoma, due to the high incidence of local relapses (8/22 patients)
      and second malignancies (n = 6 in 4/22 patients). The 5-year progression-free
      survival and overall survival rates were 42% and 66%. Mutations were inherited in
      79% of patients, and 34 additional SUFU mutation carriers were identified within
      14 families. Medulloblastoma penetrance was incomplete, but higher than in
      Patched 1 (PTCH1) mutation carriers. Besides medulloblastoma, 19 other tumors
      were recorded among the 56 SUFU mutation carriers, including basal cell carcinoma
      (BCC) in 2 patients and meningioma in 3 patients. Conclusion: Germline SUFU
      mutations strongly predispose to medulloblastoma in the first years of life, with
      worse prognosis than usually observed for SHH medulloblastoma. The clinical
      spectrum differs between SUFU and PTCH1 mutation carriers, and BCC incidence is
      much lower in SUFU mutation carriers. The optimal treatment of SUFU mutation
      associated medulloblastoma has not been defined.

PMID- 29186569
TI  - Activation Inventories after Exposure to DD/DT Neutrons in Safety Analysis of
      Nuclear Fusion Installations.
AB  - Irradiations with 14 MeV fusion neutrons are planned at Joint European Torus
      (JET) in DT operations with the objective to validate the calculation of the
      activation of structural materials in functional materials expected in ITER and
      fusion plants. This study describes the activation and dose rate calculations
      performed for materials irradiated throughout the DT plasma operation during
      which the samples of real fusion materials are exposed to 14 MeV neutrons inside
      the JET vacuum vessel. Preparatory activities are in progress during the current
      DD operations with dosimetry foils to measure the local neutron fluence and
      spectrum at the sample irradiation position. The materials included those used in
      the manufacturing of the main in-vessel components, such as ITER-grade W, Be,
      CuCrZr, 316 L(N) and the functional materials used in diagnostics and heating
      systems. The neutron-induced activities and dose rates at shutdown were
      calculated by the FISPACT code, using the neutron fluxes and spectra that were
      provided by the preceding MCNP neutron transport calculations.

PMID- 29186570
TI  - Comparative efficacy of drugs for treating giardiasis: a systematic update of the
      literature and network meta-analysis of randomized clinical trials.
AB  - Background: Giardiasis is the commonest intestinal protozoal infection worldwide.
      The current first-choice therapy is metronidazole. Recently, other drugs with
      potentially higher efficacy or with fewer and milder side effects have increased
      in popularity, but evidence is limited by a scarcity of randomized controlled
      trials (RCTs) comparing the many treatment options available. Network meta
      analysis (NMA) is a useful tool to compare multiple treatments when there is
      limited or no direct evidence available. Objectives: To compare the efficacy and
      side effects of all available drugs for the treatment of giardiasis. Methods: We
      selected all RCTs included in systematic reviews and expert reviews of all
      treatments for giardiasis published until 2014, extended the systematic
      literature search until 2016, and identified new studies by scanning reference
      lists for relevant studies. We then conducted an NMA of all available treatments
      for giardiasis by comparing parasitological cure (efficacy) and side effects.
      Results: We identified 60 RCTs from 58 reports (46 from published systematic
      reviews, 8 from reference lists and 4 from the updated systematic search). Data
      from 6714 patients, 18 treatments and 42 treatment comparisons were available.
      Tinidazole was associated with higher parasitological cure than metronidazole
      [relative risk (RR) 1.23, 95% CI 1.12-1.35] and albendazole (RR 1.35, 95% CI 1.21
      1.50). Taking into consideration clinical efficacy, side effects and amount of
      the evidence, tinidazole was found to be the most effective drug. Conclusions: We
      provide additional evidence that single-dose tinidazole is the best available
      treatment for giardiasis in symptomatic and asymptomatic children and adults.

PMID- 29186572
TI  - Hydroxycloroquine blood concentration in lupus nephritis: a determinant of
      disease outcome?
AB  - Background: Hydroxychloroquine (HCQ) is a recommended drug in systemic lupus
      erythematosus (SLE). It has a long terminal half-life, making it an attractive
      target for therapeutic drug monitoring. The aim of this study was to establish a
      relationship between blood HCQ concentration and lupus nephritis activity.
      Methods: We conducted a retrospective observational study with data collected
      from clinical and laboratory records. Inclusion criteria were patients followed
      in the lupus clinic with biopsy-proven International Society of Nephrology/Renal
      Pathology Society Classes III, IV or V lupus nephritis on HCQ for at least 3
      months (200-400 mg daily) and with HCQ levels measured during treatment.
      Exclusion criteria were patients on renal replacement therapy at baseline or
      patients lost to follow-up. Results: In 171 patients, the HCQ level was measured
      in 1282 samples. The mean HCQ blood level was 0.75+/-0.54mg/L and it was
      bimodally distributed. An HCQ level <0.20 mg/L [232 samples (18.1%)] appeared to
      define a distinct group of abnormally low HCQ levels. For patients in complete or
      partial remission at baseline compared with those remaining in remission,
      patients with renal flare during follow-up had a significantly lower average HCQ
      level (0.59 versus 0.81 mg/L; P= 0.005). Our data suggest an HCQ target level to
      reduce the likelihood of renal flares >0.6 mg/L (600 ng/mL) in those patients
      with lupus nephritis. Conclusion: HCQ level monitoring may offer a new approach
      to identify non-adherent patients and support them appropriately. We propose an
      HCQ minimum target level of at least 0.6 mg/L to reduce the renal flare rate, but
      this will require a prospective study for validation.

PMID- 29186571
TI  - Oxygen gradients can determine epigenetic asymmetry and cellular differentiation
      via differential regulation of Tet activity in embryonic stem cells.
AB  - Graded levels of molecular oxygen (O2) exist within developing mammalian embryos
      and can differentially regulate cellular specification pathways. During
      differentiation, cells acquire distinct epigenetic landscapes, which determine
      their function, however the mechanisms which regulate this are poorly understood.
      The demethylation of 5-methylcytosine (5mC) is achieved via successive oxidation
      reactions catalysed by the Ten-Eleven-Translocation (Tet) enzymes, yielding the 5
      hydroxymethylcytosine (5hmC) intermediate. These require O2 as a co-factor, and
      hence may link epigenetic processes directly to O2 gradients during development.
      We demonstrate that the activities of Tet enzymes display distinct patterns of
      [O2]-dependency, and that Tet1 activity, specifically, is subject to differential
      regulation within a range of O2 which is physiologically relevant in
      embryogenesis. Further, differentiating embryonic stem cells displayed a
      transient burst of 5hmC, which was both dependent upon Tet1 and inhibited by low
      (1%) [O2]. A GC-rich promoter region within the Tet3 locus was identified as a
      significant target of this 5mC-hydroxylation. Further, this region was shown to
      associate with Tet1, and display the histone epigenetic marks, H3K4me3 and
      H3K27me3, which are characteristic of a bivalent, developmentally 'poised'
      promoter. We conclude that Tet1 activity, determined by [O2] may play a critical
      role in regulating cellular differentiation and fate in embryogenesis.

PMID- 29186575
TI  - DNA as UV light-harvesting antenna.
AB  - The ordered structure of UV chromophores in DNA resembles photosynthetic light
      harvesting complexes in which quantum coherence effects play a major role in
      highly efficient directional energy transfer. The possible role of coherent
      excitons in energy transport in DNA remains debated. Meanwhile, energy transport
      properties are greatly important for understanding the mechanisms of
      photochemical reactions in cellular DNA and for DNA-based artificial
      nanostructures. Here, we studied energy transfer in DNA complexes formed with
      silver nanoclusters and with intercalating dye (acridine orange). Steady-state
      fluorescence measurements with two DNA templates (15-mer DNA duplex and calf
      thymus DNA) showed that excitation energy can be transferred to the clusters from
      21 and 28 nucleobases, respectively. This differed from the DNA-acridine orange
      complex for which energy transfer took place from four neighboring bases only.
      Fluorescence up-conversion measurements showed that the energy transfer took
      place within 100 fs. The efficient energy transport in the Ag-DNA complexes
      suggests an excitonic mechanism for the transfer, such that the excitation is
      delocalized over at least four and seven stacked bases, respectively, in one
      strand of the duplexes stabilizing the clusters. This result demonstrates that
      the exciton delocalization length in some DNA structures may not be limited to
      just two bases.

PMID- 29186573
TI  - Conformational dynamics of the Hop1 HORMA domain reveal a common mechanism with
      the spindle checkpoint protein Mad2.
AB  - The HORMA domain is a highly conserved protein-protein interaction module found
      in eukaryotic signaling proteins including the spindle assembly checkpoint
      protein Mad2 and the meiotic HORMAD proteins. HORMA domain proteins interact with
      short 'closure motifs' in partner proteins by wrapping their C-terminal 'safety
      belt' region entirely around these motifs, forming topologically-closed
      complexes. Closure motif binding and release requires large-scale conformational
      changes in the HORMA domain, but such changes have only been observed in Mad2.
      Here, we show that Saccharomyces cerevisiae Hop1, a master regulator of meiotic
      recombination, possesses conformational dynamics similar to Mad2. We identify
      closure motifs in the Hop1 binding partner Red1 and in Hop1 itself, revealing
      that HORMA domain-closure motif interactions underlie both Hop1's initial
      recruitment to the chromosome axis and its self-assembly on the axis. We further
      show that Hop1 adopts two distinct folded states in solution, one corresponding
      to the previously-observed 'closed' conformation, and a second more extended
      state in which the safety belt region has disengaged from the HORMA domain core.
      These data reveal strong mechanistic similarities between meiotic HORMADs and
      Mad2, and provide a mechanistic basis for understanding both meiotic chromosome
      axis assembly and its remodeling by the AAA+ ATPase Pch2/TRIP13.

PMID- 29186574
TI  - TorsinA dysfunction causes persistent neuronal nuclear pore defects.
AB  - A critical challenge to deciphering the pathophysiology of neurodevelopmental
      disease is identifying which of the myriad abnormalities that emerge during CNS
      maturation persist to contribute to long-term brain dysfunction. Childhood-onset
      dystonia caused by a loss-of-function mutation in the AAA+ protein torsinA
      exemplifies this challenge. Neurons lacking torsinA develop transient nuclear
      envelope (NE) malformations during CNS maturation, but no NE defects are
      described in mature torsinA null neurons. We find that during postnatal CNS
      maturation torsinA null neurons develop mislocalized and dysfunctional nuclear
      pore complexes (NPC) that lack NUP358, normally added late in NPC biogenesis.
      SUN1, a torsinA-related molecule implicated in interphase NPC biogenesis, also
      exhibits localization abnormalities. Whereas SUN1 and associated nuclear membrane
      abnormalities resolve in juvenile mice, NPC defects persist into adulthood. These
      findings support a role for torsinA function in NPC biogenesis during neuronal
      maturation and implicate altered NPC function in dystonia pathophysiology.

PMID- 29186576
TI  - AutDB: a platform to decode the genetic architecture of autism.
AB  - AutDB is a deeply annotated resource for exploring the impact of genetic
      variations associated with autism spectrum disorders (ASD). First released in
      2007, AutDB has evolved into a multi-modular resource of diverse types of genetic
      and functional evidence related to ASD. Current modules include: Human Gene,
      which annotates all ASD-linked genes and their variants; Animal Model, which
      catalogs behavioral, anatomical and physiological data from rodent models of ASD;
      Protein Interaction (PIN), which builds interactomes from direct relationships of
      protein products of ASD genes; and Copy Number Variant (CNV), which catalogs
      deletions and duplications of chromosomal loci identified in ASD. A multilevel
      data-integration strategy is utilized to connect the ASD genes to the components
      of the other modules. All information in this resource is manually curated by
      expert scientists from primary scientific publications and is referenced to
      source articles. AutDB is actively maintained with a rigorous quarterly data
      release schedule. As of June 2017, AutDB contains detailed annotations for 910
      genes, 2197 CNV loci, 1060 rodent models and 38 296 PINs. With its widespread use
      by the research community, AutDB serves as a reference resource for analysis of
      large datasets, accelerating ASD research and potentially leading to targeted
      drug treatments. AutDB is available at
      http://autism.mindspec.org/autdb/Welcome.do.

PMID- 29186577
TI  - Proposed Optimal Fluoroscopic Targets for Cooled Radiofrequency Neurotomy of the
      Sacral Lateral Branches to Improve Clinical Outcomes: An Anatomical Study.
AB  - Background: Current sacroiliac joint (SIJ) cooled radiofrequency (RF) is based on
      fluoroscopic anatomy of lateral branches (LBs) in three specimens. Recent studies
      confirm significant variation in LB positions. Objectives: To determine if common
      fluoroscopic needle placements for cooled SIJ RF are adequate to lesion all S1-3
      LBs. If not, would different targets improve lesion accuracy? Methods: The LBs of
      20 cadavers were dissected bilaterally (40 SIJs), and 26 G radiopaque wires were
      sutured to the LBs. With a 10-mm radius ruler centered at each foramen, standard
      targets were assessed, as judged by a clockface on the right, for S1 and S2 at
      2:30, 4:00, and 5:30 positions and at S3 at 2:30 and 4:00. Mirror image targets
      were assessed on the left. Assuming an 8-mm lesion diameter, the percentage of
      LBs that would not be ablated for each level was determined. Imaging through the
      superior end plate of S1 was compared against segment specific (SS) imaging.
      Results: Nine point four percent of LBs would not be ablated at S1 vs 0.99% at S2
      vs 35% at S3, and 60% of the 40 SIJs would be completely denervated using current
      targets. SS imaging did not improve results. Alternate target locations could
      improve the miss rate to 2.8% at S1 and 0% at S3 and would ablate all LBs in 95%
      of SIJs. Conclusions: Using a conservative 8-mm lesion measurement, contemporary
      cooled RF needle targets are inadequate to lesion all target LBs. Modifications
      to current targets are recommended to increase the effectiveness of the
      procedure.

PMID- 29186579
TI  - Insecticide Susceptibility Screening Against Culex and Aedes (Diptera: Culicidae)
      Mosquitoes From the United States.
AB  - Mosquitoes exposed to sublethal doses of insecticides may be selected for
      resistance to insecticide active ingredients (AIs). Mosquitoes are exposed to AIs
      through agricultural, public/private mosquito control programs, homeowners, and
      other sources. Hence, mosquito control programs should routinely measure the
      resistance/susceptibility status of mosquito populations of public health
      concern. The objectives here were to determine resistance status for six AIs used
      in adult mosquito control in the United States to assess how
      resistance/susceptibility differs between AI, mosquito species (states where > 1
      species collected), and between years (some populations sampled for 2 yr). Field
      collected eggs from 21 mosquito populations of six different species or hybrid
      species (Aedes albopictus Skuse [Diptera: Culicidae], Aedes aegypti L. [Diptera:
      Culicidae], Culex nigripalpus Theobald, Culex pipiens L. [Diptera: Culicidae],
      Culex quinquefasciatus Say [Diptera: Culicidae], Cx. pipiens/quinquefasciatus)
      were obtained. Centers for Disease Control and Prevention bottle bioassays were
      used to assess the resistance/susceptibility status for six AIs (bifenthrin,
      deltamethrin, etofenprox, malathion, permethrin, and phenothrin). World Health
      Organization guidelines were used to classify mosquitoes as susceptible (98-100%
      mortality at diagnostic time [DT]), possibly resistant (80-97% mortality at DT),
      or resistant (<80% mortality at DT). Significant differences were observed in
      mosquito susceptibility/resistance between species and AIs. In states where both
      Aedes and Culex were collected, the odds of exhibiting resistance in Culex were
      68-69 times higher than Aedes (Texas odds ratio: 69.30; 95% confidence interval:
      5.86, 819.44; P = 0.001; North Carolina odds ratio: 67.99; 95% confidence
      interval: 15.21, 303.94; P < 0.0001). Some level of resistance was detected
      against all tested AIs in several mosquito populations and some varied between
      2015 and 2016.

PMID- 29186578
TI  - The Planteome database: an integrated resource for reference ontologies, plant
      genomics and phenomics.
AB  - The Planteome project (http://www.planteome.org) provides a suite of reference
      and species-specific ontologies for plants and annotations to genes and
      phenotypes. Ontologies serve as common standards for semantic integration of a
      large and growing corpus of plant genomics, phenomics and genetics data. The
      reference ontologies include the Plant Ontology, Plant Trait Ontology and the
      Plant Experimental Conditions Ontology developed by the Planteome project, along
      with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and
      Attribute Ontology, and others. The project also provides access to species
      specific Crop Ontologies developed by various plant breeding and research
      communities from around the world. We provide integrated data on plant traits,
      phenotypes, and gene function and expression from 95 plant taxa, annotated with
      reference ontology terms. The Planteome project is developing a plant gene
      annotation platform; Planteome Noctua, to facilitate community engagement. All
      the Planteome ontologies are publicly available and are maintained at the
      Planteome GitHub site (https://github.com/Planteome) for sharing, tracking
      revisions and new requests. The annotated data are freely accessible from the
      ontology browser (http://browser.planteome.org/amigo) and our data repository.

PMID- 29186580
TI  - Primary maxillary sinus lymphoma.

PMID- 29186582
TI  - Safety of Spinal Cord Stimulation in Patients Who Routinely Use Anticoagulants.
AB  - Objective: We assess the safety of performing the epidural placement or revision
      of spinal cord stimulation (SCS) in patients whose anticoagulation has been held
      (termed "anticoagulant-suspended" patients) in accordance with the 2017
      Neurostimulation Appropriateness Consensus Committee (NACC) guidelines. Subjects:
      Patients undergoing SCS were included in this institutional review board-approved
      study. Design: A retrospective analysis of a prospectively collected database was
      performed. Any adverse event occurring within 90 days after SCS lead
      placement/revision was included. Results: A total of 225 patients who had a total
      of 239 surgeries including lead placement or lead revision were included; 182
      patients were not on anticoagulants, 37 patients used one anticoagulant, and six
      patients used two or more anticoagulants. There were 13 adverse events.
      Anticoagulant use as a whole had no significant relationship to operative or
      postoperative adverse effects (chi2(1) = 1.613, P > 0.05). No anticoagulant on
      its own contributed significantly to adverse events; however, a small set of
      surgical cases showed a significantly greater incidence of adverse events for
      patients on enoxaparin used in combination with other anticoagulants (P < 0.05, N
      = 4). Conclusions: This study is the first to demonstrate that anticoagulant
      suspended patients have no increased risk of perioperative hemorrhagic or
      thromboembolic adverse effects following SCS surgery compared with
      nonanticoagulated patients. The findings of this study validate the safety of
      neuromodulation in anticoagulation-suspended patients, concurring with the
      findings of previously described case studies, which anecdotally described
      neuromodulation outcomes in patients whose anticoagulation regimen had been
      temporarily held.

PMID- 29186584
TI  - Strengthening the Role of Psychiatrists in the Treatment of Chronic Pain.

PMID- 29186583
TI  - Transcriptomic Analysis of Kalopanax septemlobus and Characterization of KsBAS,
      CYP716A94 and CYP72A397 Genes Involved in Hederagenin Saponin Biosynthesis.
AB  - Kalopanax septemlobus, commonly named the castor aralia tree, is a highly valued
      woody medicinal tree belonging to the family Araliaceae. Kalopanax septemlobus
      contains approximately 15 triterpenoid saponins primarily constituted of
      hederagenin aglycones. Hederagenin is a representative precursor for hemolytic
      saponin in plants. In the present study, transcriptome analysis was performed to
      discover genes involved in hederagenin saponin biosynthesis in K. septemlobus. De
      novo assembly generated 82,698 unique sequences, including 17,747 contigs and
      64,951 singletons, following 454 pyrosequencing. Oxidosqualene cyclases (OSCs)
      are enzymes that catalyze the formation of diverse triterpene skeletons from 2,3
      oxidosqualene. Heterologous expression of an OSC sequence in yeast revealed that
      KsBAS is a beta-amyrin synthase gene. Cytochrome P450 genes (CYPs) make up a
      supergene family in the plant genome and play a key role in the biosynthesis of
      sapogenin aglycones. In total, 95 contigs and 110 singletons annotated as CYPs
      were obtained by sequencing the K. septemlobus transcriptome. By heterologous
      expression in yeast, we found that CYP716A94 was beta-amyrin 28-oxidase involved
      in oleanolic acid production from beta-amyrin, and CYP72A397 was oleanolic acid
      23-hydroxylase involved in hederagenin production from oleanolic acid. Engineered
      yeast co-expressing KsBAS, CYP716A94 and CYP72A397 produced hederagenin.
      Kalopanax septemlobus CYP72A397 is a novel CYP enzyme that synthesizes
      hederagenin aglycone from oleanolic acid as a single product. In conclusion, we
      characterized three genes participating in sequential steps for hederagenin
      biosynthesis from beta-amyrin, which are likely to play a major role in
      hederagenin saponin biosynthesis in K. septemlobus.

PMID- 29186581
TI  - Type-B ARRs Control Carpel Regeneration Through Mediating AGAMOUS Expression in
      Arabidopsis.
AB  - Plants are known for their capacity to regenerate organs, such as shoot, root and
      floral organs. Recently, a number of studies contributed to understanding the
      mechanisms of shoot and root regeneration. However, the mechanisms underlying
      floral organ regeneration are largely unknown. In this study, we established a
      carpel regeneration system in which two types of carpels were induced by
      exogenous cytokinin. For type I, all the floral organs in the regenerated
      inflorescence were transformed into carpels. For type II, carpels were generated
      directly from callus. The transcript level of AGAMOUS (AG), the carpel identity
      gene, was up-regulated during carpel induction. The expression signals of AG were
      detected in the initiating carpel primordia and regenerating carpels, and co
      localized with those of two Type-B ARABIDOPSIS RESPONSE REGULATORs (ARRs), ARR1
      and ARR10. Repression of either AG or type-B ARRs reduced carpel regeneration.
      Binding analyses showed that ARR1 and ARR10 directly bound to transcriptional
      regulatory regions of AG and positively regulated its expression. In addition,
      the expression of type-B ARRs overlapped with that of AG in the floral primordia
      in planta. Defects in type-B ARRs reduced the number of carpels. The results
      indicate that type-B ARRs control carpel regeneration through activating AG
      expression. Our results provide new information for understanding the mechanism
      of carpel formation.

PMID- 29186585
TI  - Fatality Following Ingestion of Tetrahydrofuranylfentanyl, U-49900 and Methoxy
      Phencyclidine.
AB  - Novel psychoactive substances (NPS), and specifically novel opioids, continue to
      cause adverse events, including death, within drug-using populations. As the
      number of opioid-related overdoses continues to increase, laboratories have
      identified the emergence of new fentanyl analogues and other synthetic opioid
      related drugs. Tetrahydrofuranylfentanyl (THFF) has been identified in Europe and
      the United States as an emerging novel opioid, causing death in at least 15 drug
      using individuals to date. THFF is structurally similar to furanylfentanyl, a
      previously characterized novel opioid responsible for numerous adverse events,
      including death. In this case report, THFF, U-49900 and methoxy-phencyclidine
      were identified in postmortem blood and urine specimens collected after a
      suspected overdose. As part of the death investigation, an unknown substance was
      collected from the scene and analytically confirmed as THFF and U-49900. To
      further assist laboratories in identifying THFF ingestion, metabolic profiling
      was conducted using pooled human liver microsomes. Characterized metabolites were
      then confirmed in the specimens collected during this investigation. In total,
      seven metabolites were identified for THFF, most notably THF-norfentanyl and
      hydroxyl-THFF. THF-norfentanyl provides utility as a biomarker because it is a
      unique metabolite of THFF. 4-Anilino-N-phenethylpiperidine (4-ANPP) and its
      metabolite, hydroxyl-4-ANPP, were identified in microsomal incubations and
      collected specimens, but usefulness as biomarkers is limited due to commonality
      between other fentanyl analogues and co-ingestion as a synthesis precursor. To
      our knowledge, this case report is the first to document a fatality after
      ingestion of THFF and U-49900 in the United States.

PMID- 29186586
TI  - Relationship between stomatal density, size and speed of opening in Sumatran
      rainforest species.
AB  - Recent studies have suggested that an association between size and speed of
      stomatal opening of stomata within taxa is likely to play a role in
      photosynthesis and transpiration. In this study we investigate whether this
      correlation applies for seedlings of 11 rainforest species from different taxa,
      and whether differences in stomatal and gas exchange parameters were related to
      initial growth under field and controlled conditions. The experiment was
      conducted on seedlings of nine late successional species and two early
      successional species, placed in full sunlight or 70% shade. We assessed density,
      size, length and width of guard cells, coupled with gas exchange parameters in
      the transition from darkness to light, recording minimum stomatal conductance
      during daytime darkness (gs-dark), operating maximum stomatal conductance (gs
      op), speed of stomatal opening and the time to reach 50% conductance (T-50%). All
      stomata and gas exchange parameters were different between species. Shade
      significantly affected size and density, and all gas exchange parameters except
      gs-op were different between light situations. Stomatal size correlated
      negatively with speed of opening and positively with T-50%, confirming that
      smaller stomata open faster than large stomata. The two early successional
      species were very different in stomatal size and density, and in response to
      light. Anatomic parameters and physiological traits were not related to height
      growth, but gs-dark, gs-op and speed of stomatal opening were associated with
      biomass growth in a subselection of six late successional species.

PMID- 29186587
TI  - Effective Online Bayesian Phylogenetics via Sequential Monte Carlo with Guided
      Proposals.
AB  - Modern infectious disease outbreak surveillance produces continuous streams of
      sequence data which require phylogenetic analysis as data arrives. Current
      software packages for Bayesian phylogenetic inference are unable to quickly
      incorporate new sequences as they become available, making them less useful for
      dynamically unfolding evolutionary stories. This limitation can be addressed by
      applying a class of Bayesian statistical inference algorithms called sequential
      Monte Carlo (SMC) to conduct online inference, wherein new data can be
      continuously incorporated to update the estimate of the posterior probability
      distribution. In this article, we describe and evaluate several different online
      phylogenetic sequential Monte Carlo (OPSMC) algorithms. We show that proposing
      new phylogenies with a density similar to the Bayesian prior suffers from poor
      performance, and we develop "guided" proposals that better match the proposal
      density to the posterior. Furthermore, we show that the simplest guided proposals
      can exhibit pathological behavior in some situations, leading to poor results,
      and that the situation can be resolved by heating the proposal density. The
      results demonstrate that relative to the widely used MCMC-based algorithm
      implemented in MrBayes, the total time required to compute a series of
      phylogenetic posteriors as sequences arrive can be significantly reduced by the
      use of OPSMC, without incurring a significant loss in accuracy.

PMID- 29186588
TI  - Cohort Profile: The Yazd Health Study (YaHS): a population-based study of adults
      aged 20-70 years (study design and baseline population data).

PMID- 29186591
TI  - Diffuse Papulovesicular Rash in an Infant With Eczema.

PMID- 29186590
TI  - Frequency of Multidrug-Resistant Organisms Cultured From Urine of Children
      Undergoing Clean Intermittent Catheterization.
AB  - Background: Children undergoing CIC frequently have positive urine culture
      results and receive many antimicrobial agents. Subsequently, this population is
      at high risk for infections caused by antimicrobial-resistant bacteria. Resistant
      pathogens, such as vancomycin-resistant Enterococcus (VRE), carbapenem-resistant
      Enterobacteriaceae (CRE), and organisms that produce extended-spectrum beta
      lactamases (ESBLs), which are third-generation cephalosporin resistant (3GCR),
      are of particular concern. Methods: In this retrospective study, all urine
      culture results and antimicrobial-susceptibility testing results were obtained
      between January 2008 and December 2014 from the electronic health record of
      children <=18 years of age who were undergoing CIC (n = 14 832). Isolates were
      identified as VRE, CRE, or 3GCR. Organisms of the same type that were obtained in
      the same year and with identical antibiotic susceptibilities from the same
      patient were excluded. Simple linear regression was used to determine the
      association between year and rates of resistance. Results: A total of 3997
      positive culture results were included in this analysis. Of all Enterococcus
      isolates for which susceptibility results were available, 4.6% were VRE, 11.1% of
      all isolates that belonged to the Enterobacteriaceae family were 3GCR, and 0.4%
      of eligible isolates were CRE. There were significantly higher rates of
      resistance to third-generation cephalosporins and CRE in 2014 than in 2008 (P <
      .01). Simple linear regression revealed a significant association between year
      and rate for resistance to third-generation cephalosporins but not for CRE or
      VRE. The rate of increase in resistance to third-generation cephalosporins in
      patients who required CIC was higher than that in patients who did not need CIC.
      Conclusions: The rate of resistance to third-generation cephalosporins has
      increased significantly in the past 7 years in children undergoing CIC, which
      indicates that careful monitoring is warranted for continued increases in
      antimicrobial-resistant organisms in this unique patient population.

PMID- 29186589
TI  - Detergent Insoluble Proteins and Inclusion Body-Like Structures Immunoreactive
      for PRKDC/DNA-PK/DNA-PKcs, FTL, NNT, and AIFM1 in the Amygdala of Cognitively
      Impaired Elderly Persons.
AB  - Misfolded protein in the amygdala is a neuropathologic feature of Alzheimer
      disease and many other neurodegenerative disorders. We examined extracts from
      human amygdala (snap-frozen at autopsy) to investigate whether novel and as yet
      uncharacterized misfolded proteins would be detectable. Polypeptides from the
      detergent-insoluble, urea-soluble protein fractions of amygdala were interrogated
      using liquid chromatography-electrospray ionization-tandem mass spectrometry.
      Among the detergent-insoluble proteins identified in amygdala of demented
      subjects but not controls were Tau, TDP-43, Abeta, alpha-synuclein, and ApoE.
      Additional detergent-insoluble proteins from demented subjects in the high
      molecular weight portion of SDS gels included NNT, TNIK, PRKDC (DNA-PK, or DNA
      PKcs), ferritin light chain (FTL), AIFM1, SYT11, STX1B, EAA1, COL25A1, M4K4,
      CLH1, SQSTM, SYNJ1, C3, and C4. In follow-up immunohistochemical experiments,
      NNT, TNIK, PRKDC, AIFM1, and FTL were observed in inclusion body-like structures
      in cognitively impaired subjects' amygdalae. Double-label immunofluorescence
      revealed that FTL and phospho-PRKDC immunoreactivity colocalized partially with
      TDP-43 and/or Tau inclusion bodies. Western blots showed high-molecular weight
      "smears", particularly for NNT and PRKDC. A preliminary genetic association study
      indicated that rare NNT, TNIK, and PRKDC gene variants had nominally significant
      association with Alzheimer-type dementia risk. In summary, novel detergent
      insoluble proteins, with evidence of proteinaceous deposits, were found in
      amygdalae of elderly, cognitively impaired subjects.

PMID- 29186592
TI  - Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis
      modalities: a meta-analysis of published studies.
AB  - Background: Recent meta-analyses suggest that higher removal of beta-2
      microglobulin (beta2M) with either high-flux (HFD) dialysis or hemodiafiltration
      (HDF) may be associated with decreased total and cardiovascular mortality in
      dialysis patients. However, there are limited data about the performance of high
      flux dialyzers and/or convective therapies in removing beta2M. Methods: This is a
      random effects meta-analysis and meta-regression of data extracted from
      randomized controlled trials and observational studies in hemodialysis,
      hemofiltration and HDF regarding the efficiency of high flux dialyzers to remove
      beta2M. Studies were searched using ProQuest in SCOPUS, EMBASE and MEDLINE.
      Results: We included 69 studies from 1 January 2001 to 12 June 2017 on 1879
      patients with 6771 available measurements. Average beta2M clearance was 48.75
      mL/min [95% confidence interval (CI) 42.50-55.21] for conventional HF dialysis,
      and 87.06 mL/min (95% CI 75.08-99.03) for convective therapies (hemofiltration
      and HDF) with substantial heterogeneity among studies [P (Q) <= 0.001]. In
      multivariable meta-regression analyses, we found significantly higher beta2M
      clearance for polyarylethersulfone dialyzers when used for HFD and polysulfone
      membranes in convective therapies. However, the mass of beta2M removed into the
      dialysate did not depend on membrane material. Adjusted dialysate-side (-22.279,
      95% CI  -9.8 to -34.757, P < 0.001) beta2M clearances were significantly lower
      than whole blood clearances, suggesting that adsorption contributes substantially
      to beta2M removal. Higher Kuf, blood flow and substitution fluid rates but not
      dialysate flow rates were associated with statistically significant and
      clinically meaningful elevation in beta2M clearance from the body independent of
      the dialysis modality. Conclusions: Membrane composition and characteristics,
      modality (convective versus diffusive), blood flow rates and substitution fluid
      rates in HDF play a significant role in the efficient removal of beta2M from the
      body in both diffusive and convective dialysis.

PMID- 29186593
TI  - Complex Models of Sequence Evolution Require Accurate Estimators as Exemplified
      with the Invariable Site Plus Gamma Model.
AB  - The invariable site plus $?Gamma$ model (I$+?Gamma)$ is widely used to model rate
      heterogeneity among alignment sites in maximum likelihood and Bayesian
      phylogenetic analyses. The proof that the I$+$ continuous $?Gamma$ model is
      identifiable (model parameters can be inferred correctly given enough data) has
      increased the creditability of its application to phylogeny reconstruction.
      However, most phylogenetic software implement the I$+$ discrete $?Gamma$ model,
      whose identifiability is likely but unproven. How well the parameters of the I$+$
      discrete $?Gamma$ model are estimated is still disputed. Especially the
      correlation between the fraction of invariable sites and the fractions of sites
      with a slow evolutionary rate is discussed as being problematic. We show that
      optimization heuristics as implemented in frequently used phylogenetic software
      (PhyML, RAxML, IQ-TREE, and MrBayes) cannot always reliably estimate the shape
      parameter, the proportion of invariable sites, and the tree length. Here, we
      propose an improved optimization heuristic that accurately estimates the three
      parameters. While research efforts mainly focus on tree search methods, our
      results signify the equal importance of verifying and developing effective
      estimation methods for complex models of sequence evolution.

PMID- 29186594
TI  - Resection of Temporal Neocortex During Multiple Hippocampal Transections for
      Mesial Temporal Lobe Epilepsy Does not Affect Seizure or Memory Outcome.
AB  - BACKGROUND: Multiple hippocampal transection (MHT) is a surgical treatment for
      mesial temporal lobe epilepsy associated with improved postoperative
      neuropsychological outcomes compared with lobectomy. OBJECTIVE: To determine
      whether resection of the amygdala and anterior temporal neocortex during MHT
      affects postoperative seizure/memory outcome. METHODS: Seventeen patients with
      normal magnetic resonance imaging and stereo-electroencephalogram-proven drug
      resistant dominant mesial temporal lobe epilepsy were treated with MHT. Nine
      patients underwent MHT alone (MHT-) and 8 patients underwent MHT plus removal of
      the amygdala and anterior 4.5 cm of temporal neocortex lateral to the fusiform
      gyrus (MHT+). Verbal and visual-spatial memory were assessed in all patients
      preoperatively and in 14 patients postoperatively using the Wechsler Memory
      Scale. Postoperative seizure control was assessed at 12 months for all patients.
      RESULTS: Overall, 11 of 17 patients (64.7%) were Engel class 1 at 1 year (6/9 MHT
      , 5/8 MHT+, P = .38), and 10 of 14 patients (71.4%) had no significant
      postoperative decline in either verbal or visual memory (6/8 MHT-, 4/6 MHT+, P =
      .42). Verbal memory declined in 2 of 8 MHT- and 1 of 6 MHT+ patients, and visual
      memory declined in 1 of 8 MHT- and 2 of 6 MHT+ patients. Two patients had
      improved visual memory postoperatively, both in the MHT+ group. CONCLUSION: MHT
      on the dominant side is associated with high rates of seizure freedom and
      favorable memory preservation outcomes regardless of the extent of neocortical
      resection. Preservation of the temporal neocortex and amygdala during MHT does
      not appear to decrease the risk of postoperative memory decline, nor does it
      alter seizure outcome.

PMID- 29186595
TI  - Treatment of Recurrent Intracranial Aneurysms After Neck Clipping: Novel
      Classification Scheme and Management Strategies.
AB  - BACKGROUND: Recurrent aneurysms after initial clipping have been discussed as an
      important issue in the surgical management of aneurysm. OBJECTIVE: To report our
      experience with recurrent cerebral aneurysms after neck clipping and to discuss
      classification and recommended management. METHODS: Aneurysm treatments from a
      single institution over a 20-year period were retrospectively reviewed. Twenty
      three recurrent aneurysms in 23 patients were managed during the study period.
      Recurrent aneurysms were classified using the concepts of closure line and
      closure plane, as follows. Type 1: neck situated in an almost different site from
      the previous clip. Type 2: existing closure plane and reconstructive closure
      plane are almost the same. Type 3: existing closure plane and reconstructive
      closure plane cross (type 3a); in rare cases, the existing closure line is
      sufficiently distant from the neck (type 3b). Type 4: no reconstructive closure
      line is identifiable. RESULTS: Nine patients presented with subarachnoid
      hemorrhage at recurrence. The mean interval to recurrence was 15.0 years.
      Management comprised clipping with elective subsequent old-clip removal (n = 7),
      clipping with preceding old-clip removal (n = 2), bypass occlusion (n = 1),
      coating (n = 1), combined surgery (n = 1), endovascular surgery (n = 4), and
      observation (n = 3). Therapeutic intervention was not indicated in 4 patients.
      Types 3a and 4 required more complex surgical procedures or coil embolization.
      Procedural complications were observed in 2 patients. CONCLUSION: A small but
      definite propensity toward recurrence after neck clipping exists, and most
      recurrent aneurysms require some form of retreatment. The novel classification
      scheme may provide conceptual clarity and therapeutic guidance for decision
      making.

PMID- 29186596
TI  - Long-Standing Scalp Retraction Technique Using an External Fixator for Sunken
      Skin Flap Syndrome.
AB  - BACKGROUND AND IMPORTANCE: The authors report a novel external scalp retraction
      technique for sunken skin flap syndrome (SSFS). CLINICAL PRESENTATION: A 48-year
      old male patient suffered neurological deterioration due to SSFS after
      decompressive craniectomy. Cranioplasty is the gold standard for therapeutic
      management of SSFS, but could not be performed due to intracranial wound
      infection. The patient underwent external fixation of a metal plate as a frame
      for the skull and the scalp was pulled outward to the frame by skin suture. The
      patient returned to daily activities at home for 3 months with this scalp
      traction frame, which was needed for infection control. CONCLUSION: External
      scalp traction is useful for the temporary relief of pressure caused by SSFS.

PMID- 29186597
TI  - Factors for a Good Surgical Outcome in Posterior Decompression and Dekyphotic
      Corrective Fusion with Instrumentation for Thoracic Ossification of the Posterior
      Longitudinal Ligament: Prospective Single-Center Study.
AB  - BACKGROUND: Surgery for thoracic ossification of the posterior longitudinal
      ligament (T-OPLL) is still challenging, and factors for good surgical outcomes
      are unknown. OBJECTIVE: To identify factors for good surgical outcomes with
      prospective and comparative study. METHODS: Seventy-one consecutive patients who
      underwent posterior decompression and instrumented fusion were divided into good
      or poor outcome groups based on >=50% and <50% recovery rates for the Japanese
      Orthopaedic Association score. Preoperative, intraoperative, and postoperative
      findings were compared in the 2 groups, and significant factors for a good
      outcome were analyzed. RESULTS: Patients with a good outcome (76%) had
      significantly lower nonambulatory rate and positive prone and supine position
      tests preoperatively; lower rates of T-OPLL, ossification of the ligamentum
      flavum, high-intensity area at the same level, thoracic spinal cord alignment
      difference, and spinal canal stenosis on preoperative magnetic resonance imaging;
      lower estimated blood loss; higher rates of intraoperative spinal cord floating
      and absence of deterioration of intraoperative neurophysiological monitoring; and
      lower rates of postoperative complications (P < .0005). In multivariate logistic
      regression analysis, negative prone and supine position test (odds ratio [OR]:
      17.00), preoperative ambulatory status (OR: 6.05), absence of T-OPLL,
      ossification of the ligamentum flavum, high-intensity area at the same level (OR:
      5.84), intraoperative spinal cord floating (OR: 4.98), and lower estimated blood
      loss (OR: 1.01) were significant factors for a good surgical outcome. CONCLUSION:
      This study demonstrated that early surgery is recommended during these positive
      factors. Appropriate surgical planning based on preoperative thoracic spinal cord
      alignment difference, as well as sufficient spinal cord decompression and
      reduction of complications using intraoperative ultrasonography and
      intraoperative neurophysiological monitoring, may improve surgical outcomes.

PMID- 29186598
TI  - Favorable Long-Term Functional Outcomes and Safety of Auditory Brainstem Implants
      in Nontumor Patients.
AB  - BACKGROUND: Auditory brainstem implants (ABIs) were designed to restore hearing
      in deaf patients with auditory tumors or those unable to receive cochlear
      implants. Although ABIs may help some patients, their long-term outcomes have
      been rarely studied. OBJECTIVE: To assess the long-term benefits and safety of
      ABIs in nontumor patients with sensorineural hearing loss (SNHL). METHODS: We
      retrospectively reviewed the histories of 15 deaf patients (8 females, 7 males;
      mean age, 15.5 yr; range, 1-56 yr) who received ABIs for treatment of SNHL at our
      hospital from July 2008 to November 2015. These included 11 children with narrow
      internal auditory canals and 4 deaf adults with severe cochlear ossification. In
      each patient, a 12-channel ABI electrode was placed in the cochlear nucleus
      complex via a retrosigmoid approach. Auditory performance was evaluated using the
      Categories of Auditory Performance (CAP) index and sound detection and word
      identification tests. RESULTS: One year after ABI placement, 13 of 15 patients
      showed adequate or significantly improved auditory function based on the CAP
      scores at the last follow-up. Generally, adult patients tended to show better CAP
      scores (3.50) than pediatric patients (2.15), but the difference was not
      significant (P = .058). Postoperative complications included electrode migration,
      cerebrospinal fluid leakage, nonauditory stimulation, and minor seizures without
      severe sequelae or mortality. CONCLUSION: ABIs show favorable functional outcomes
      and long-term safety in nontumor deaf patients with limited treatment options.
      Collectively, our data indicate that ABIs represent an important treatment option
      for SNHL.

PMID- 29186599
TI  - T-Connector Modification for Reducing Recurrent Distal Shunt Failure: Report of 2
      Cases.
AB  - BACKGROUND AND IMPORTANCE: Cerebrospinal fluid shunt placement is used to treat
      the various causes of hydrocephalus by redirecting the cerebrospinal fluid to the
      body, most commonly from the ventricle to the peritoneum. Distal catheter
      displacement from the peritoneal cavity can occur as a complication,
      necessitating reoperation. CLINICAL PRESENTATION: We report 2 such cases in obese
      patients involving retropulsion of the distal tubing. To address this
      complication, we implanted a T-connector to the distal catheter construct.
      CONCLUSION: This study supports the use of a T-connector catheter construct to
      decrease and prevent the possibility of distal peritoneal catheter retropulsion
      in cases of elevated intra-abdominal pressure, both prophylactically and in
      revisions.

PMID- 29186600
TI  - An in Vitro Biomechanical Model of Differing Pedicle Screw Configurations for
      Long Construct Segmental Thoracic Fixation.
AB  - BACKGROUND: The optimum pattern of pedicle screw (PS) fixation during long
      segment thoracic fixation has not been determined. OBJECTIVE: To evaluate rod
      stress and construct stability with minimal, alternating, skipped, and bilateral
      PS constructs in the iatrogenically destabilized thoracic spine. METHODS: Eight
      cadaveric thoracic specimens (T3-T12) were initially tested intact to +/-5 Nm
      using a custom 6 degree-of-freedom spine testing apparatus in flexion-extension
      (FE), lateral bending (LB), and axial rotation. Specimens were instrumented with
      T4-T10 bilateral PS, with Ponte osteotomies to introduce instability. Rods were
      bent to fit the PS and then spines were tested with the minimal, alternating,
      skipped, and bilateral fixation patterns. Range of motion (ROM) was calculated
      from T4-T10 and segmentally. In addition, strain gauges fixed to the spinal rods
      measured rod stress under FE and LB. Results were compared using ANOVA and post
      hoc Holm Sidak tests. RESULTS: All fixation patterns provided significant
      reductions in ROM with respect to the intact spine. In all motion planes, minimal
      provided the least amount of rigidity, while bilateral provide the greatest;
      however, no statistically significant differences were detected in FE. In LB and
      axial rotation, skipped, alternating, and bilateral were all significantly more
      rigid than minimal (P < .01). Rod strains were greatest under LB and correlated
      with overall construct ROM, where bilateral had significantly lower strain than
      the other patterns (P < .05). CONCLUSION: All constructs effectively decreased
      thoracic ROM. There was significant improvement in stabilization and decreased
      rod stress when more fixation points beyond the minimal construct were included.

PMID- 29186601
TI  - Microsurgical Endoscope-Assisted Gravity-Aided Transfalcine Approach for
      Contralateral Metastatic Deep Medial Cortical Tumors.
AB  - BACKGROUND: Traditional approaches to deep medial cortical tumors utilize
      transcortical or ipislateral interhemispheric approaches, which can result in
      cortical damage or retraction injury. To reduce these risks, the microscopic
      transfalcine approach has been previously described. OBJECTIVE: To describe this
      approach performed with endoscopic assistance for metastatic tumor resection,
      demonstrating appropriate and safe tumor resection without injury to the
      contralateral hemisphere. METHODS: Eleven consecutive patients harboring medial,
      deep metastatic tumors are reported. Tumor resection was performed with
      endoscopic assistance with 2 surgeons. Clinical outcomes are recorded. RESULTS:
      All 11 patients underwent safe tumor resection. Gross total resection was
      achieved in 73% of patients. The application of the angled endoscope allowed for
      further tumor resection in 91% of patients. There were no complications in these
      patients. The contralateral brain did not demonstrate clinical or radiographic
      injury as well. CONCLUSION: This series suggests that the endoscopic transfalcine
      approach in the lateral position can be a safe and effective approach for
      resecting medial interhemispheric metastatic tumors. It allows excellent tumor
      visualization, eliminates the need for brain retraction, minimizes parenchymal
      transgression, and improves surgical ergonomics. A familiarity of endoscopy and
      neuroanesthesia support is helpful when utilizing this approach.

PMID- 29186602
TI  - Intraoperative Computed Tomography Angiography: A Novel Completion Imaging
      Modality for Carotid Endarterectomy.
AB  - BACKGROUND: Intraoperative computed tomography angiography (ICTA) is a novel
      completion imaging modality for carotid endarterectomy (CEA). No studies exist in
      the literature describing ICTA use in CEA. OBJECTIVE: To evaluate the feasibility
      and efficacy of ICTA as a method of immediately evaluating the technical results
      of CEA. METHODS: Twenty-three consecutive CEAs were performed by a single
      neurosurgeon over an 8-month period. Of this series, 12 utilized ICTA for
      completion imaging, 10 utilized duplex ultrasonography (US), and 1 utilized no
      intraoperative completion imaging. Electronic medical records were reviewed to
      assess demographics, CTA results, US results, and need for revisions. RESULTS:
      Patients included 13 men (62%) and 8 women (38%). All patients had symptomatic
      internal carotid artery stenosis. Polytetrafluoroethylene (PTFE) patch
      angioplasty was used in 16 cases (70%). Average operative times were comparable
      between cases that utilized CTA and US, 180 and 175 min, respectively. Major
      technical defects were identified in one of the 12 cases utilizing ICTA and none
      of the 10 cases utilizing intraoperative US. The technical defect was revised
      without subsequent neurological complication. One patient had a postoperative
      intracerebral hemorrhage requiring surgical evacuation. Fifteen patients were
      followed for up to 3 months with no postoperative stroke or transient ischemic
      attacks. CONCLUSION: ICTA is a potentially safe and effective completion imaging
      modality compared to traditional alternatives, enabling the identification of
      technical deficits intraoperatively. While no statistically significant
      difference in operative times were noted between intraoperative CTA and US use,
      numerous steps must be taken to maximize the efficiency of ICTA.

PMID- 29186603
TI  - Integrated Multimaneuver Dissection Technique of the Sylvian Fissure: Operative
      Nuances.
AB  - BACKGROUND: Several intracranial pathologies require opening the Sylvian fissure
      to be approached, and they are traditionally accessed through the frontal side of
      the superficial Sylvian veins. The integrated multimaneuver dissecting technique
      (IMMDT) interchanges the steps with the veins still secured for safe dissection,
      but the Sylvian fissure is approached from the optimal, safe side with integrated
      techniques. OBJECTIVE: To determine whether the 1-way dissection of the Sylvian
      fissure converts to the more favorable and flexible IMMDT. METHODS: The IMMDT for
      the Sylvian fissure was used on all our patients. The selected subjects (n = 3)
      had different pathologies, radiological data, and pre- and postoperative clinical
      data. These subjects were reviewed retrospectively. RESULTS: The 3 patients
      presented with different pathologies necessitating opening the Sylvian fissure.
      The Sylvian fissure was not simple in all cases. In all 3 cases, the Sylvian
      veins and their branches were saved, as confirmed by postoperative images. The
      patients all had good neurological outcomes, with either stable or improved
      modified Rankin Scale at the last follow-up. CONCLUSION: This study demonstrated
      that the IMMDT is a safe alternative to other ways of opening a Sylvian fissure
      composed of complex venous anatomy. The IMMDT aligned the fissure in multiple
      directions to the exposed trajectory, optimized its approach for a flexible, safe
      dissection, allowed the instruments to work into the Sylvian fissure, and
      facilitated exposure of the deep part of the fissure for the final dissection,
      all without scarifying any structure.

PMID- 29186604
TI  - A3-A3 In Situ Bypass and Distal Clip Occlusion of Giant Serpentine Anterior
      Communicating Artery Aneurysm: 3-Dimensional Operative Video.

PMID- 29186605
TI  - Contralateral Transfalcine Resection of Splenial Arteriovenous Malformation: 3
      Dimensional Operative Video.

PMID- 29186606
TI  - Technique of Minimally Invasive Cervical Foraminotomy.
AB  - BACKGROUND: Posterior cervical foraminotomy is a long utilized and commonly
      performed procedure, but has been supplanted in many cases by anterior
      procedures. With the advent of minimally invasive techniques, posterior
      foraminotomy may again deserve a prominent place in the treatment of cervical
      foraminal stenosis. OBJECTIVE: To report in detail a successfully utilized
      minimally invasive technique and the results in a large series of patients, by a
      single author. METHODS: The technique is described and illustrated in detail. A
      retrospective review of the use of this technique in a large series is reported.
      RESULTS: Precise details of the technique are described with specific attention
      to complication avoidance. In over 360 cases, there have been no nerve root
      injuries other than idiopathic C5 palsies, no wound infections, and a single
      durotomy that required no specific treatment. CONCLUSION: Minimally invasive
      posterior cervical foraminotomy is a well-tolerated and effective procedure which
      can be performed with minimal complications when attention to detail is
      maintained.

PMID- 29186607
TI  - Benefits and Limitations of Indocyanine Green Fluorescent Image-Guided Surgery
      for Spinal Intramedullary Tumors.
AB  - BACKGROUND: Intraoperative image guidance using near-infrared indocyanine green
      videoangiography (ICG-VA) has been used to provide real-time angiographic images
      during vascular or brain tumor surgery, and it is also being used for spine
      surgery. OBJECTIVE: To further investigate the benefits and limitations of ICG-VA
      image-guided surgery for spinal intramedullary tumors through retrospective
      study. METHODS: ICG-VA was used in 48 cases that were treated surgically over the
      past 5 yr. The pathological diagnoses of the tumors included astrocytic tumor,
      ependymal tumor, cavernous malformation, and hemangioblastoma. RESULTS:
      Localization of normal spinal arteries and veins on the dorsal surface of the
      spinal cord helped the surgeons determine the length or point of myelotomy. Well
      demarcated tumor stain was recognized in limited cases of anaplastic or highly
      vascularized tumors, whereas the location of cavernous malformation was
      recognized as an avascular area on the dorsal surface of the spinal cord. Feeding
      arteries and tumor stain were well differentiated from draining veins in dorsal
      hemangioblastomas, but not in intramedullary deep-seated or ventral tumors. The
      preservation of small perforating branches of the anterior spinal artery after
      successful resection of the tumor could be well visualized. CONCLUSION: ICG-VA
      can provide real-time information about vascular flow dynamics during the surgery
      of spinal intramedullary tumors, and it may help surgeons localize the normal
      circulation of the spinal cord, as well as the feeding arteries and draining
      veins, especially in highly vascular tumors. However, the benefits of
      intraoperative ICG-VA might be limited for intramedullary deep-seated or ventral
      tumors.

PMID- 29186608
TI  - Supratonsillar Approach to Deep Cerebellar Cavernous Malformations Near the
      Dentate Nucleus: 3-Dimensional Operative Video.

PMID- 29186609
TI  - Transsylvian Resection of Dominant Insular Gliomas: Demonstration of
      Microsurgical Techniques in Pure Insular vs Insulo-Opercular Gliomas: 3
      Dimensional Operative Video.

PMID- 29186610
TI  - Microscopic Resection of Recurrent Giant Adenoma and Clip Ligation of
      Contralateral Internal Carotid Artery Terminus Aneurysm: 3-Dimensional Operative
      Video.

PMID- 29186611
TI  - Suboccipital Craniotomy and Clip Occlusion of a Precoiled Recurrent Distal
      Posterior Inferior Cerebellar Artery Aneurysm: Operative Video.

PMID- 29186612
TI  - Examining the Potential Role of Foliar Chemistry in Imparting Potato Germplasm
      Tolerance to Potato Psyllid, Green Peach Aphid, and Zebra Chip Disease.
AB  - Long-term, sustainable management of zebra chip disease of potato, caused by
      'Candidatus Liberibacter solanacearum' (Lso) and vectored by potato psyllids
      (Bactericera cockerelli Sulc [Hemiptera: Triozidae]), requires development of
      cultivars resistant or tolerant to infection or capable of reducing spread or
      both. We examined the influence that five experimental breeding clones of potato
      had on potato psyllids and their ability to vector Lso. The ability of these
      potato clones to resist aphids (green peach aphids, Myzus persicae Sulzer
      [Hemiptera: Aphididae]) also was examined. Due to the importance of host
      chemistry on plant-insect interactions, levels of primary metabolites of amino
      acids and sugars, as well as secondary metabolites including polyphenolics,
      terpenoids, and alkaloids were compared between breeding clones and a commercial
      cultivar. Findings for compound levels then were associated with observed changes
      in host susceptibility to psyllids or aphids. Psyllids oviposited less on three
      breeding clones than Atlantic, but no significant effects of breeding clones on
      psyllid feeding or choice were observed. Aphid reproduction was reduced on two
      clones relative to Atlantic. A05379-211 had greater sugar levels and postpsyllid
      amino acid levels than Atlantic. Total alkaloid and phenolic levels were greater
      in all breeding clones than Atlantic. Total terpenoid levels were greater in
      PALB03016-3 and PALB03016-6 than Atlantic, which might explain, in part, the
      observed resistance to psyllid oviposition and aphid reproduction. Overall, these
      results suggest that increased levels of certain metabolites in breeding clones
      could affect psyllid and aphid reproduction.

PMID- 29186614
TI  - L-Carnitine Attenuates Cardiac Dysfunction by Ischemic Insults Through Akt
      Signaling Pathway.

PMID- 29186613
TI  - Biochemical and structural characterization of a novel cooperative binding mode
      by Pit-1 with CATT repeats in the macrophage migration inhibitory factor
      promoter.
AB  - Overexpression of the proinflammatory cytokine macrophage migration inhibitory
      factor (MIF) is linked to a number of autoimmune diseases and cancer. MIF
      production has been correlated to the number of CATT repeats in a microsatellite
      region upstream of the MIF gene. We have characterized the interaction of
      pituitary-specific positive transcription factor 1 (Pit-1) with a portion of the
      MIF promoter region flanking a microsatellite polymorphism (-794 CATT5-8). Using
      fluorescence anisotropy, we quantified tight complex formation between Pit-1 and
      an oligonucleotide consisting of eight consecutive CATT repeats (8xCATT) with an
      apparent Kd of 35 nM. Using competition experiments we found a 23 base pair
      oligonucleotide with 4xCATT repeats to be the minimum DNA sequence necessary for
      high affinity interaction with Pit-1. The stoichiometry of the Pit-1 DNA
      interaction was determined to be 2:1 and binding is cooperative in nature. We
      subsequently structurally characterized the complex and discovered a completely
      novel binding mode for Pit-1 in contrast to previously described Pit-1 complex
      structures. The affinity of Pit-1 for the CATT target sequence was found to be
      highly dependent on cooperativity. This work lays the groundwork for
      understanding transcriptional regulation of MIF and pursuing Pit-1 as a
      therapeutic target to treat MIF-mediated inflammatory disorders.

PMID- 29186616
TI  - JUNB governs a feed-forward network of TGFbeta signaling that aggravates breast
      cancer invasion.
AB  - It is well established that transforming growth factor-beta (TGFbeta) switches
      its function from being a tumor suppressor to a tumor promoter during the course
      of tumorigenesis, which involves both cell-intrinsic and environment-mediated
      mechanisms. We are interested in breast cancer cells, in which SMAD mutations are
      rare and interactions between SMAD and other transcription factors define pro
      oncogenic events. Here, we have performed chromatin immunoprecipitation (ChIP)
      sequencing analyses which indicate that the genome-wide landscape of SMAD2/3
      binding is altered after prolonged TGFbeta stimulation. De novo motif analyses of
      the SMAD2/3 binding regions predict enrichment of binding motifs for activator
      protein (AP)1 in addition to SMAD motifs. TGFbeta-induced expression of the AP1
      component JUNB was required for expression of many late invasion-mediating genes,
      creating a feed-forward regulatory network. Moreover, we found that several
      components in the WNT pathway were enriched among the late TGFbeta-target genes,
      including the invasion-inducing WNT7 proteins. Consistently, overexpression of
      WNT7A or WNT7B enhanced and potentiated TGFbeta-induced breast cancer cell
      invasion, while inhibition of the WNT pathway reduced this process. Our study
      thereby helps to explain how accumulation of pro-oncogenic stimuli switches and
      stabilizes TGFbeta-induced cellular phenotypes of epithelial cells.

PMID- 29186617
TI  - POPULATION RADIATION EXPOSURE FROM DIAGNOSTIC NUCLEAR MEDICINE PROCEDURES IN
      TEHRAN 2011-14; TRENDS IN THE LAST 3 DECADES.
AB  - This study represents an update of Tehran population exposure from the diagnostic
      nuclear medicine procedures and the annual collective effective dose during 2011
      14. The diagnostic nuclear medicine procedures data were collected from 58 out of
      60 nuclear medicine centers in Tehran and were composed of the type and frequency
      of diagnostic examinations, radiopharmaceuticals used, administered activities,
      and age distribution of the patients. The annual number of examinations per 1000
      population increased from 13.73 in 2011 to 22.59 in 2014 with an increase of
      64.53% during 4 years. Most frequent examinations were cardiac (71.05%), bone
      (9.80%) and thyroid (7.26%) averaged over the 5 years. The collective effective
      dose increased from 807.74 person-Sv in 2011 to 1413.81 person-Sv in 2014. The
      effective dose per capita increased from 44.06 MUSv in 2011 to 120.91 MUSv in
      2014, could be because of 70% increase of examinations, but ~3.42% increase in
      the population of Tehran.

PMID- 29186618
TI  - Semi-automatized segmentation method using image-based flow cytometry to study
      sperm physiology: the case of capacitation-induced tyrosine phosphorylation.
AB  - STUDY QUESTION: Is image-based flow cytometry a useful tool to study
      intracellular events in human sperm such as protein tyrosine phosphorylation or
      signaling processes? SUMMARY ANSWER: Image-based flow cytometry is a powerful
      tool to study intracellular events in a relevant number of sperm cells, which
      enables a robust statistical analysis providing spatial resolution in terms of
      the specific subcellular localization of the labeling. WHAT IS KNOWN ALREADY:
      Sperm capacitation is required for fertilization. During this process,
      spermatozoa undergo numerous physiological changes, via activation of different
      signaling pathways, which are not completely understood. Classical approaches for
      studying sperm physiology include conventional microscopy, flow cytometry and
      Western blotting. These techniques present disadvantages for obtaining detailed
      subcellular information of signaling pathways in a relevant number of cells. This
      work describes a new semi-automatized analysis using image-based flow cytometry
      which enables the study, at the subcellular and population levels, of different
      sperm parameters associated with signaling. The increase in protein tyrosine
      phosphorylation during capacitation is presented as an example. STUDY DESIGN
      SIZE, DURATION: Sperm cells were isolated from seminal plasma by the swim-up
      technique. We evaluated the intensity and distribution of protein tyrosine
      phosphorylation in sperm incubated in non-capacitation and capacitation
      supporting media for 1 and 18 h under different experimental conditions. We used
      an antibody against FER kinase and pharmacological inhibitors in an attempt to
      identify the kinases involved in protein tyrosine phosphorylation during human
      sperm capacitation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen samples from
      normospermic donors were obtained by masturbation after 2-3 days of sexual
      abstinence. We used the innovative technique image-based flow cytometry and image
      analysis tools to segment individual images of spermatozoa. We evaluated and
      quantified the regions of sperm where protein tyrosine phosphorylation takes
      place at the subcellular level in a large number of cells. We also used
      immunocytochemistry and Western blot analysis. Independent experiments were
      performed with semen samples from seven different donors. MAIN RESULTS AND THE
      ROLE OF CHANCE: Using image analysis tools, we developed a completely novel semi
      automatic strategy useful for segmenting thousands of individual cell images
      obtained using image-based flow cytometry. Contrary to immunofluorescence which
      relies on the analysis of a limited sperm population and also on the observer,
      image-based flow cytometry allows for unbiased quantification and simultaneous
      localization of post-translational changes in an extended sperm population.
      Interestingly, important data can be independently analyzed by looking to the
      frame of interest. As an example, we evaluated the capacitation-associated
      increase in tyrosine phosphorylation in sperm incubated in non-capacitation and
      capacitation-supporting media for 1 and 18 h. As previously reported, protein
      tyrosine phosphorylation increases in a time-depending manner, but our method
      revealed that this increase occurs differentially among distinct sperm segments.
      FER kinase is reported to be the enzyme responsible for the increase in protein
      tyrosine phosphorylation in mouse sperm. Our Western blot analysis revealed for
      the first time the presence of this enzyme in human sperm. Using our segmentation
      strategy, we aimed to quantify the effect of pharmacological inhibition of FER
      kinase and found a marked reduction of protein tyrosine phosphorylation only in
      the flagellum, which corresponded to the physical localization of FER in human
      sperm. Our method provides an alternative strategy to study signaling markers
      associated with capacitation, such as protein tyrosine phosphorylation, in a fast
      and quantitative manner. LARGE SCALE DATA: None. LIMITATIONS REASONS FOR CAUTION:
      This is an in vitro study performed under controlled conditions. Chemical
      inhibitors are not completely specific for the intended target; the possibility
      of side effects cannot be discarded. WIDER IMPLICATIONS OF THE FINDINGS: Our
      results demonstrate that the use of image-based flow cytometry is a very powerful
      tool to study sperm physiology. A large number of cells can be easily analyzed
      and information at the subcellular level can be obtained. As the segmentation
      process works with bright-field images, it can be extended to study expression of
      other proteins of interest using different antibodies or it can be used in living
      sperm to study intracellular parameters that can be followed using fluorescent
      dyes sensitive to the parameter of interest (e.g. pH, Ca2+). Therefore, this a
      versatile method that can be exploited to study several aspects of sperm
      physiology. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported
      DGAPA (IN203116 to C. Trevino), Fronteras-CONACyT No. 71 and Eunice Kennedy
      Shriver National Institute of Child Health and Human Development NIH (RO1
      HD38082) to P.E. Visconti and by a Lalor Foundation fellowship to M.G. Gervasi.
      A. Matamoros is a student of the Maestria en Ciencias Bioquimicas-UNAM program
      supported by CONACyT (416400) and DGAPA-UNAM. A. Moreno obtained a scholarship
      from Red MacroUniversidades and L. Giojalas obtained a schloarhip from CONICET
      and Universidad Nacional de Cordoba. The authors declare there are not conflicts
      of interest.

PMID- 29186620
TI  - The Feeling Prosthesis-Somatosensory Feedback from the Prosthesis Foot Reduces
      Phantom Limb Pain Dramatically.

PMID- 29186619
TI  - Multisite Machine Learning Analysis Provides a Robust Structural Imaging
      Signature of Schizophrenia Detectable Across Diverse Patient Populations and
      Within Individuals.
AB  - Past work on relatively small, single-site studies using regional volumetry, and
      more recently machine learning methods, has shown that widespread structural
      brain abnormalities are prominent in schizophrenia. However, to be clinically
      useful, structural imaging biomarkers must integrate high-dimensional data and
      provide reproducible results across clinical populations and on an individual
      person basis. Using advanced multi-variate analysis tools and pooled data from
      case-control imaging studies conducted at 5 sites (941 adult participants,
      including 440 patients with schizophrenia), a neuroanatomical signature of
      patients with schizophrenia was found, and its robustness and reproducibility
      across sites, populations, and scanners, was established for single-patient
      classification. Analyses were conducted at multiple scales, including regional
      volumes, voxelwise measures, and complex distributed patterns. Single-subject
      classification was tested for single-site, pooled-site, and leave-site-out
      generalizability. Regional and voxelwise analyses revealed a pattern of
      widespread reduced regional gray matter volume, particularly in the medial
      prefrontal, temporolimbic and peri-Sylvian cortex, along with ventricular and
      pallidum enlargement. Multivariate classification using pooled data achieved a
      cross-validated prediction accuracy of 76% (AUC = 0.84). Critically, the leave
      site-out validation of the detected schizophrenia signature showed accuracy/AUC
      range of 72-77%/0.73-0.91, suggesting a robust generalizability across sites and
      patient cohorts. Finally, individualized patient classifications displayed
      significant correlations with clinical measures of negative, but not positive,
      symptoms. Taken together, these results emphasize the potential for structural
      neuroimaging data to provide a robust and reproducible imaging signature of
      schizophrenia. A web-accessible portal is offered to allow the community to
      obtain individualized classifications of magnetic resonance imaging scans using
      the methods described herein.

PMID- 29186622
TI  - Psychiatry and Pain Management.

PMID- 29186624
TI  - Local and Systemic Inflammation May Mediate Diesel Engine Exhaust-Induced Lung
      Function Impairment in a Chinese Occupational Cohort.
AB  - Diesel exhaust (DE) as the major source of vehicle-emitted particle matter in
      ambient air impairs lung function. The objectives were to assess the contribution
      of local (eg, the fraction of exhaled nitric oxide [FeNO] and serum Club cell
      secretory protein [CC16]) and systemic (eg, serum C-reaction protein [CRP] and
      interleukin-6 [IL-6]) inflammation to DE-induced lung function impairment using a
      unique cohort of diesel engine testers (DETs, n = 137) and non-DETs (n = 127),
      made up of current and noncurrent smokers. Urinary metabolites, FeNO, serum
      markers, and spirometry were assessed. A 19% reduction in CC16 and a 94% increase
      in CRP were identified in DETs compared with non-DETs (all p values <10-4), which
      were further corroborated by showing a dose-response relationship with internal
      dose for DE exposure (all p values <.04) and a time-course relationship with DE
      exposure history (all p values <.005). Mediation analysis showed that 43% of the
      difference in FEV1 between DETs and non-DETs can be explained by circulating CC16
      and CRP (permuted p < .001). An inverse dose-dependent relationship between FeNO
      and internal dose for cigarette smoke was identified (p = .0003). A range of 95%
      lower bounds of benchmark dose of 1.0261-1.4513 MUg phenanthrols/g creatinine in
      urine as an internal dose was recommended for regulatory risk assessment. Local
      and systemic inflammation may be key processes that contribute to the subsequent
      development of obstructive lung disease in DE-exposed populations.

PMID- 29186623
TI  - Developmental origins of health and disease: current knowledge and potential
      mechanisms.
AB  - Epidemiologic and clinical research has provided a large body of evidence
      supporting the developmental origins of health and disease (DOHaD), but there has
      been a relative dearth of mechanistic studies in humans due to the complexity of
      working with large, longitudinal cohorts. Nonetheless, animal models of
      undernutrition have provided substantial evidence for the potential epigenetic,
      metabolic, and endocrine mechanisms behind DOHaD. Furthermore, recent research
      has explored the interaction between the environment and the gastrointestinal
      system by investigating how the gut microbial ecology may impact the capacity for
      nutrient processing and absorption in a manner that may limit growth. This review
      presents a summary of current research that supports the concept of DOHaD, as
      well as potential mechanisms and interactions that explain how nutrition in utero
      and during early childhood influences lifelong health.

PMID- 29186625
TI  - Lesbian Motherhood and the Artificial Insemination by Donor Scandal of 1978.
AB  - In January 1978, the London Evening News informed its readers of its shocking
      discovery that British lesbians were conceiving babies by artificial insemination
      by donor (AID). Assisted by a respected London gynaecologist, Dr David Sopher,
      the women were planning and raising children in the context of lesbian
      relationships, challenging conventional family models and the widespread
      presumption that lesbianism and motherhood were mutually exclusive identities.
      The debate which was sparked by the Evening News expose and taken up in
      Parliament, the national and local media and on the streets in the subsequent
      weeks, offers an insight into attitudes towards lesbian motherhood in the late
      1970s. This article explores constructions of lesbian mothers and the impact on
      the experiences and identities of lesbian mothers themselves. The late 1970s
      marked the beginnings of a shift in practices of conception by British lesbians
      from lesbians who conceived their children in the context of previous
      heterosexual relationships, to women who utilized AID and other forms of donor
      insemination to forge new family structures, and this article analyses the
      stories of some of these women as they emerged from the 1978 debate.

PMID- 29186626
TI  - Contested Spaces: London and the 1984-5 Miners' Strike.
AB  - The 1984-5 British miners' strike can be understood as a defence of place as well
      as jobs. Such a conception encourages us to foreground the local in accounts of
      the strike. However, I argue in this article that the local should not be
      understood in an excessively bounded way. By paying attention to relationships
      developed between London and the coalfields during the dispute, we can see how
      direct personal networks of solidarity were constructed between these very
      different places. This article discusses the spaces in which solidarity activity
      for miners in London took place. I argue that political activists rooted
      themselves in localities by constructing permanent spaces such as centres and
      bookshops, which enabled the development of concrete relationships between
      different places. I highlight 'twinning' as a distinct spatial tactic used by
      supporters of the strike to bridge geographical distance and develop personal
      connections between London and the coalfields. I also show that elements of the
      state were used to both sustain this solidarity and to restrict the space
      available for the miners and their supporters. I argue centrally, therefore, that
      opposing political visions for moving beyond the post-war settlement manifested
      in a struggle over space in the 1980s.

PMID- 29186621
TI  - Is the voice an auditory face? An ALE meta-analysis comparing vocal and facial
      emotion processing.
AB  - This meta-analysis compares the brain structures and mechanisms involved in
      facial and vocal emotion recognition. Neuroimaging studies contrasting emotional
      with neutral (face: N = 76, voice: N = 34) and explicit with implicit emotion
      processing (face: N = 27, voice: N = 20) were collected to shed light on stimulus
      and goal-driven mechanisms, respectively. Activation likelihood estimations were
      conducted on the full data sets for the separate modalities and on reduced,
      modality-matched data sets for modality comparison. Stimulus-driven emotion
      processing engaged large networks with significant modality differences in the
      superior temporal (voice-specific) and the medial temporal (face-specific)
      cortex. Goal-driven processing was associated with only a small cluster in the
      dorsomedial prefrontal cortex for voices but not faces. Neither stimulus- nor
      goal-driven processing showed significant modality overlap. Together, these
      findings suggest that stimulus-driven processes shape activity in the social
      brain more powerfully than goal-driven processes in both the visual and the
      auditory domains. Yet, whereas faces emphasize subcortical emotional and mnemonic
      mechanisms, voices emphasize cortical mechanisms associated with perception and
      effortful stimulus evaluation (e.g. via subvocalization). These differences may
      be due to sensory stimulus properties and highlight the need for a modality
      specific perspective when modeling emotion processing in the brain.

PMID- 29186627
TI  - Rethinking Folk Culture in Twentieth-Century Britain.
AB  - Research on folk culture in twentieth-century Britain has focused on elite and
      transgressive political episodes, but these were not its mainstream
      manifestations. This article re-evaluates the place of folk culture in twentieth
      century Britain in the context of museums. It argues that in the modern heritage
      landscape folk culture was in an active dialogue with the modern democracy. This
      story begins with the vexed, and ultimately failed, campaign for a national
      English folk museum and is traced through the concurrent successes of local,
      regional, and Celtic 'first wave' folk museums across Britain from the 1920s to
      the 1960s. The educational activities of these museums are explored as emblematic
      of a 'conservative modernity', which gave opportunities to women but also
      restricted their capacity to do intellectual work. By the 1970s, a 'second wave'
      folk museology is identified, revealing how forms of folk culture successfully
      accommodated the rapid social change of the later twentieth century, particularly
      in deindustrializing regions. From this new, museums' perspective, folk culture
      appears far less marginal to twentieth-century British society. In museums folk
      culture interacted with mainstream concerns about education, regionalism, and
      commercialization.

PMID- 29186628
TI  - The Complex Holiday Calendar of 1902: Responses to the Coronation of Edward VII
      and the Growth of Edwardian Event Fatigue.
AB  - The coronation of Edward VII and events to mark the end of the South African War
      led to a series of public ceremonies and events in the United Kingdom that had a
      profound effect on attitudes linked to national occasions and public holidays.
      This article explores the circumstances surrounding the numerous local and
      national holidays of 1902. It considers the decision-making process linked to the
      declaration of a coronation double-bank holiday, which demonstrated the
      inadequacy of contemporary legislation. The public response to the postponement
      of the coronation, due to the king's contraction of appendicitis, led to a period
      of 'event fatigue' in response to further ceremonial events. This showcased how
      much the British people guarded their right to holiday time and how the
      coronation had become more synonymous with celebration than with royal ceremony.
      It also showcased the degree to which the British people had been politicized and
      were ready to defend what they saw as their rights, in rejection of deference and
      traditional authority.

PMID- 29186629
TI  - Tutankhamen, Egyptomania, and Temporal Enchantment in Interwar Britain.

PMID- 29186630
TI  - Music models aberrant rule decoding and reward valuation in dementia.
AB  - Aberrant rule- and reward-based processes underpin abnormalities of socio
      emotional behaviour in major dementias. However, these processes remain poorly
      characterized. Here we used music to probe rule decoding and reward valuation in
      patients with frontotemporal dementia (FTD) syndromes and Alzheimer's disease
      (AD) relative to healthy age-matched individuals. We created short melodies that
      were either harmonically resolved ('finished') or unresolved ('unfinished'); the
      task was to classify each melody as finished or unfinished (rule processing) and
      rate its subjective pleasantness (reward valuation). Results were adjusted for
      elementary pitch and executive processing; neuroanatomical correlates were
      assessed using voxel-based morphometry. Relative to healthy older controls,
      patients with behavioural variant FTD showed impairments of both musical rule
      decoding and reward valuation, while patients with semantic dementia showed
      impaired reward valuation but intact rule decoding, patients with AD showed
      impaired rule decoding but intact reward valuation and patients with progressive
      non-fluent aphasia performed comparably to healthy controls. Grey matter
      associations with task performance were identified in anterior temporal, medial
      and lateral orbitofrontal cortices, previously implicated in computing diverse
      biological and non-biological rules and rewards. The processing of musical rules
      and reward distils cognitive and neuroanatomical mechanisms relevant to complex
      socio-emotional dysfunction in major dementias.

PMID- 29186632
TI  - Integrating sequence and gene expression information predicts genome-wide DNA
      binding proteins and suggests a cooperative mechanism.
AB  - DNA-binding proteins (DBPs) perform diverse biological functions ranging from
      transcription to pathogen sensing. Machine learning methods can not only identify
      DBPs de novo but also provide insights into their DNA-recognition dynamics.
      However, it remains unclear whether available methods that can accurately predict
      DNA-binding sites in known DBPs can also identify novel DBPs. Moreover, sequence
      information is blind to the cellular- and disease-specific contexts of DBP
      activities, whereas the under-utilized knowledge from public gene expression data
      offers great promise. To address these issues, we have developed novel methods
      for predicting DBPs by integrating sequence and gene expression-derived features
      and applied them to explore human, mouse and Arabidopsis proteomes. While our
      sequence-based models outperformed the gene expression-based ones, some proteins
      with weaker DBP-like sequence features were correctly predicted by gene
      expression-based features, suggesting that these proteins acquire a tangible DBP
      functionality in a conducive gene expression environment. Analysis of motif
      enrichment among the co-expressed genes of top 100 candidates DBPs from hitherto
      unannotated genes provides further avenues to explore their functional
      associations.

PMID- 29186634
TI  - A Model to Integrate Health Promotion and Wellness in Physical Therapist
      Practice: Development and Validation.
AB  - Background: Globally, physical therapy professional organizations have called for
      physical therapists to perform lifestyle behavior management during customary
      care, or health-focused care, due to increasing morbidity and mortality related
      to noncommunicable diseases. Given the potential for health-focused care to
      improve health outcomes, physical therapists should integrate health promotion
      into their daily clinical practice. A clinical model that illustrates necessary
      steps to deliver health-focused care would be helpful to educate present and
      future physical therapists. Objective: The purpose of the study was to develop
      and validate the Health-Focused Physical Therapy Model (HFPTM) for physical
      inactivity and smoking. Methods: The authors used a mixed method approach. The
      preliminary model was informed by previous research and the investigators' shared
      experience in health promotion and physical therapy. An interdisciplinary group
      of health professionals provided input into the preliminary model by way of a
      World Cafe format. Eight physical therapists with health promotion and education
      expertise then engaged in a Delphi process to establish content validity.
      Results: World Cafe participants indicated that: (1) physical therapists are well
      positioned to engage in health promotion and wellness, and (2) the model
      facilitates interdisciplinary collaboration and consultation. Delphi process
      participants reached majority consensus in 1 round. The average model content
      validity index (CVI) was .915 for physical inactivity and .899 for smoking.
      Agreement concerning the model schematic was 88% for either behavior.
      Investigators made few editorial changes after the Delphi process. Limitations:
      Limitations of this study include using only 2 unhealthy lifestyle behaviors for
      testing, and performing the testing in a nonclinical setting. Conclusions: An
      interdisciplinary group of health professionals believes that physical therapists
      should practice health-focused care and that the HFPTM is a valid model. This
      model could help physical therapist educators when educating physical therapist
      students and clinicians to practice health-focused care.

PMID- 29186633
TI  - Family-centered Care Improved Neonatal Medical and Neurobehavioral Outcomes in
      Preterm Infants: Randomized Controlled Trial.
AB  - Background: Family-centered care for preterm infants in Western societies has
      yielded short- to medium-term benefits. However, the intervention effects have
      rarely been validated in Eastern societies. Objective: The aim of this study was
      to examine whether a family-centered intervention program (FCIP) could improve
      the short-term medical and neurobehavioral outcomes in preterm infants with very
      low birth weight (VLBW; a birth weight of <1,500 g) in Taiwan over the outcomes
      seen with a usual care program (UCP). Design: This was a multicenter, single
      blind, randomized controlled trial study. Setting: Three medical centers in
      northern and southern Taiwan were the locations for the study. Participants: The
      participants were 251 VLBW preterm infants without severe perinatal
      complications. Intervention: The infants were randomly assigned to receive the
      FCIP or the UCP during hospitalization. Measurements: Infant morbidities,
      feeding, growth, and neurobehavioral performance were evaluated during the
      neonatal period. Parental adherence to interventions was measured in the FCIP
      group. Results: The FCIP promoted earlier full enteral feeding (beta = -1.1
      weeks; 95% CI = -1.9 to -0.2 weeks) and hospital discharge (beta = -0.6 week; 95%
      CI = -1.1 to -0.1 weeks), greater weight gain (beta = 3.3 g/d; 95% CI = 0.1 to
      6.6 g/d), and better neurobehavioral performance than the UCP (beta = 1.2 points;
      95% CI = 0.2 to 2.3 points). Furthermore, a higher degree of parental motivation
      in interventions, goal attainment, and comprehensiveness of home activities was
      significantly associated with greater effects in infants' neurobehavioral
      performance and weight gain (r = .20-.31; all Ps < .05). Limitations: The
      findings may not be generalized to preterm infants with severe perinatal diseases
      and parents with a low level of interest in interventions. Conclusions: Family
      centered care facilitated short-term medical and neurobehavioral outcomes in VLBW
      preterm infants in Taiwan; the effects were likely achieved through parental
      adherence to interventions. The designated strategies may be considered in a
      future launch of family-centered care in Taiwan.

PMID- 29186636
TI  - A New Breed of Rehabilitation Scientists.

PMID- 29186635
TI  - Identification of Indirect Effects in a Cognitive Patient Education (COPE)
      Intervention for Low Back Pain.
AB  - Background: Many interventions for the treatment of low back pain exist, but the
      mechanisms through which such treatments work are not always clear. This
      situation is especially true for biopsychosocial interventions that incorporate
      several different components and methods of delivery. Objective: The study
      objective was to examine the indirect effects of the Cognitive Patient Education
      (COPE) intervention via illness perceptions, back pain myths, and pain
      catastrophizing on disability outcome. Design: This study was a secondary
      analysis of the COPE randomized controlled trial. Methods: Mediation analysis
      techniques were employed to examine the indirect effects of the COPE intervention
      via residualized change (baseline - posttreatment) in the 3 variables
      hypothesized to be targeted by the COPE intervention on posttreatment disability
      outcome. Pain intensity at baseline, pain duration, clinician type, and a
      treatment-mediator interaction term were controlled for in the analysis. Results:
      Preliminary analyses confirmed that changes in pain catastrophizing and illness
      perceptions (not back pain myths) were related to both allocation to the
      intervention arm and posttreatment disability score. The treatment exerted
      statistically significant indirect effects via changes in illness perceptions and
      pain catastrophizing on posttreatment disability score (illness perceptions
      standardized indirect effect = 0.09 [95% CI = 0.03 to 0.16]; pain catastrophizing
      standardized indirect effect = 0.05 [95% CI = 0.01 to 0.12]). However, the
      inclusion of an interaction term led to the indirect effects being significantly
      reduced, with the effects no longer being statistically significant. Limitations:
      This study presents a secondary analysis of variables not identified a priori as
      being potentially important treatment targets; other, unmeasured factors could
      also be important in explaining treatment effects. Conclusions: The finding that
      small indirect effects of the COPE intervention via changes in illness
      perceptions and pain catastrophizing on posttreatment disability could be
      estimated indicates that these variables may be viable treatment targets for
      biopsychosocial interventions; however, this finding must be viewed in light of
      the adjusted analyses, which showed that the indirect effects were significantly
      reduced through the inclusion of a treatment-mediator interaction term.

PMID- 29186637
TI  - Factors associated with upper leg muscle strength in knee osteoarthritis: A
      scoping review.
AB  - OBJECTIVE: Muscle weakness is common and strongly related to clinical outcome in
      patients with knee or hip osteoarthritis. To date, there is no clear overview of
      the information on factors associated with muscle strength in knee and hip
      osteoarthritis. The aim of this paper is to provide an overview of current
      knowledge on factors associated with upper leg muscle strength in this
      population. DESIGN: The framework of a scoping review was chosen. MEDLINE
      database was searched systematically up to 22 April 2017. Studies that described
      a relationship between a factor and muscle strength in knee or hip osteoarthritis
      were included. RESULTS: A total of 65 studies met the inclusion criteria. In
      studies of knee osteoarthritis, 4 factors were consistently found to be
      associated with lower muscle strength. Due to the low number of studies on hip
      osteoarthritis no conclusions could be drawn on associations. CONCLUSION: Lower
      muscle quality, physical inactivity, more severe joint degeneration, and higher
      pain are reported to be associated with lower strength in the upper leg muscles
      in knee osteoarthritis. Future research into knee osteoarthritis should focus on
      other potential determinants of muscle strength, such as muscle quantity, muscle
      activation, nutrition and vitamins, and inflammation. In hip osteoarthritis, more
      research is needed into all potential determinants.

PMID- 29186638
TI  - Stent-over-sponge (SOS): a novel technique complementing endosponge therapy for
      foregut leaks and perforations.
AB  - BACKGROUND AND STUDY AIMS: Endoluminal vacuum therapy (EVT) has evolved as a
      promising option for endoscopic treatment of foregut wall injuries in addition to
      the classic closure techniques using clips or stents. To improve vacuum force and
      maintain esophageal passage, we combined endosponge treatment with a partially
      covered self-expandable metal stent (stent-over-sponge; SOS). PATIENTS AND
      METHODS: Twelve patients with infected upper gastrointestinal wall defects were
      treated with the SOS technique. RESULTS: Indications for SOS were anastomotic
      leakage after surgery (n = 11) and chronic foregut fistula (n = 1). SOS treatment
      was used as a first-line treatment in seven patients with a success rate of 71.4
      % (5/7) and as a second-line treatment after failed previous EVT treatment in
      five patients (success rate 80 %; 4/5). Overall, SOS treatment was successful in
      75 % of patients (9/12). No severe adverse events occurred. CONCLUSION : SOS is
      an effective method to treat severely infected foregut wall defects in patients
      where EVT has failed, and also as a first-line treatment. Comparative prospective
      studies are needed to confirm our preliminary results.

PMID- 29186639
TI  - Interferon-free cure of chronic Hepatitis C is associated with weight gain during
      long-term follow-up.
AB  - Background and aim The advent of direct-acting antivirals has revolutionized
      treatment of chronic hepatitis C with very high cure rates and excellent
      tolerability compared to interferon-based hepatitis C virus (HCV) treatment.
      However, long-term effects of interferon-free cure of HCV infection on the
      metabolic condition of patients have not been investigated so far. Methods We
      investigated weight development during and after antiviral treatment of hepatitis
      C. In a prospective single-center cohort study, interferon-free antiviral
      treatment was initiated in 284 patients. Each patient's weight was monitored 1
      year before the start of treatment, at baseline (BL), end of treatment (EOT),
      follow-up week 24 (FU24), and follow-up week 48 (FU48). Results Weight gain after
      HCV cure was observed in 20 %, 33 %, and 44 % of patients at EOT, FU24, and FU48,
      respectively. The mean overall weight change at FU48 compared to baseline was
      1.45 kg (95 % CI 0.44; 2.46, p = 0.02, compared to the pretreatment period).
      Multivariate regression revealed age as the only factor predicting weight change
      at FU48 (B - 0.107, 95 % CI, - 0.202 to - 0.011, p = 0.03), while gender,
      cirrhosis, diabetes mellitus, ribavirin, and body mass index had no influence. In
      the subgroup of patients younger than 60 years, mean weight gain at FU48 compared
      to baseline was 2.8 kg (95 % CI, 1.23 - 4.4). In contrast, patients 60 years and
      older had a mean weight change of - 0.04 kg (95 % CI, - 1.12 to 1.03, p = 0.005).
      Conclusions Cure of HCV by interferon-free antiviral treatment was associated
      with weight gain in up to 44 % of patients during long-term follow-up. Weight
      gain occurred predominantly in patients younger than 60 years. The precise
      mechanism of weight gain remains to be elucidated.

PMID- 29186640
TI  - [Esomeprazol-induced cutaneous lupus erythematosus].
AB  - Proton pump inhibitors are among the most commonly used drugs worldwide. They are
      considered to be largely safe and cause little side-effects. We report a 69-year
      old woman who suffered from erythematous plaques 2 months after initiating
      therapy with esomeprazole. The diagnosis of subacute cutaneous lupus
      erythematosus was based on the clinical picture together with characteristic
      histological features of a skin biopsy specimen and the detection of anti-Ro/SSA
      antibodies. In particular, the temporal relationship with the onset of proton
      pump inhibitor therapy led to the high-level suspicion of a drug-induced
      pathogenesis. Strengthening the initially suspected diagnosis, the characteristic
      skin lesions resolved almost completely without specific therapy after
      discontinuation of the medication. If typical skin lesions occur in light-exposed
      areas in connection with the administration of PPI, the possibility of a drug
      induced cutaneous lupus erythematosus should always be considered. Due to the
      frequent recurrence rate after renewed exposure, a new therapy with PPI should be
      avoided.

PMID- 29186641
TI  - Gut microbiota and colorectal cancer: insights into pathogenesis for novel
      therapeutic strategies.
AB  - Colorectal cancer (CRC), as a leading cause of cancer-related death, is triggered
      by the complex interplay of host genetics and environmental factors. Mounting
      evidence has shed light on the association of the gut microbiota dysbiosis with
      CRC. In CRC experimental models, certain gut microbial strains have been shown to
      inhibit or attenuate immune responses, indicating that specific species among
      intestinal commensal bacteria may play either a pathogenic or a protective role
      in the development of CRC. Oral intake of probiotics/prebiotics can therefore
      serve as a therapeutic approach for CRC treatment. Microbiota studies in cancer,
      however, are still at the early stage, lack of quantitative data for clinic
      application. Fortunately, sequencing-based technologies are a boon to further
      investigation on the association of the intestinal bacterial flora and human
      diseases. This review considers the evidence for the role of the gut microbiota
      in CRC development and progression, responsiveness to immune system, and the
      related therapeutic applications of probiotics/prebiotics.

PMID- 29186642
TI  - [FLOT becomes standard neoadjuvant chemotherapy for adenocarcinoma of the
      esophagogastric junction and stomach].

PMID- 29186644
TI  - ?

PMID- 29186645
TI  - [Editorial.News from ICN Congress 2017 and CNAI Manifesto for nursing board
      elections in Italy].

PMID- 29186643
TI  - [S2k Guideline Gastrointestinal Bleeding - Guideline of the German Society of
      Gastroenterology DGVS].

PMID- 29186646
TI  - [How staff perceives head nurses' leadership: a qualitative study].
AB  - BACKGROUND: The leadership style of the head nurses plays a crucial role in
      ensuring a work environment that fosters high quality nursing care. Their role
      involves a range of activities that constantly change, and is therefore difficult
      to describe. In fact, we do not have a fixed set of characteristics to define the
      'ideal candidate'. AIM: To understand how staff defines the key leadership
      characteristics of the ideal head nurse in charge of a hospital ward. METHOD:
      Between April-July 2015, 27 nurses were selected from the departments of general
      medicine in five hospitals. Three focus groups were conducted to identify the key
      leadership characteristics of an ideal head nurse. RESULTS: The ideal leadership
      characteristics are expressed through actions of staff empowerment, management
      skills, and use of coping strategies. All these categories require that a leader
      should be strongly determined, resourceful, enthusiastic, and willing to be a
      leader. When balancing 'what you give and receive', the main difficulty of being
      a leader is to be sufficiently determined to avoid exhaustion, which leads to
      emotional disengagement and consequently the loss of the leadership role.
      CONCLUSIONS: The level of determination of a head nurse, just like any source of
      energy, may sway. Therefore, it is important to recognize the signs of exhaustion
      and identify the strategy to rekindle determination. Sharing one's vision with
      others and job rotation could be used as strategies to recharge a leader's levels
      of energy, and meet the expectations linked to the leader's role. KEY WORDS:
      nurse manager, leadership style, determination, job rotation, vision.

PMID- 29186647
TI  - [Students, clinical nurse preceptors and academic tutors' perception and
      experience in relation to the implementation of a Dedicated Education Unit: a
      qualitative study using focus group.]
AB  - OBJECTIVE: analyse students, clinical nurse preceptors and academic tutors'
      perception and experience further to the implementation of a Dedicated Education
      Unit (DEU) in a pulmonary medicine ward. METHOD: The study follows a qualitative
      descriptive method. Data have been collected through focus groups (FGs). We have
      organized four different FGs, a specific focus group for each stakeholder
      (students, nurses and tutors) and a closing one with everybody. Each FG followed
      a qualitative content analysis method. Students had to fill in the CLES+T
      questionnaire to confirm qualitative data. RESULTS: Participants: 6 tutors, 7
      nurses and 10 students (i.e. 6 first-year, 2 second-year and 2 third-year
      students). The experience has been positive. We have found four different themes,
      both cross-sectional and specific, in relation to positive aspects. 1. Briefing
      and debriefing as discussion and learning opportunities (cross-sectional); 2.
      Peer education potentialities (cross-sectional); 3. Global and holistic care
      (students); 4. Academic tutors as ward resources (cross-sectional). In relation
      to critical aspects, instead, we have highlighted a macro-theme, which refers to
      "Organizational peculiarities" and is composed of three subthemes: 1. Workload
      (tutors and nurses); 2. Inhomogeneity in nurses and tutors' behaviour/attitude
      (cross-sectional); 3. Lack of a personal relationship between students and
      training assistants (students). All the ameliorative proposals are related to
      organizational peculiarities. CONCLUSION: This study reports the first Italian
      experimentation of the DEU training organization model. The experience has been
      very positive: it has not only promoted a moment's reflection but also provided
      the opportunity for both the Clinical and the Academic setting to discuss and
      collaborate to reach the common goal, i.e. best student learning.

PMID- 29186648
TI  - [Is repositioning regimen effective to prevent pressure injuries? Synopsis of
      systematic reviews.]
AB  - INTRODUCTION: Repositioning regimen is an intervention recommended by guidelines
      and traditionally used in daily care practice but its benefit for preventing
      pressure injuries (PI) is not clinically proved. OBJECTIVE: To determine the
      effect of repositioning regimen to prevent PI. METHODS: A research on five
      electronic databases (The Cochrane Library, Medline, Embase, CINAHL, Web of
      Science) was conducted on March 23, 2017. Records returned by the search strategy
      were independently analyzed and those that respected inclusion criteria have been
      found in full text. In synopsis have been included systematic reviews of
      controlled clinical trials or quasi-experimental studies that compare
      repositioning regimen with usual care. The AMSTAR checklist has been used for
      quality evaluation. RESULTS: Five systematic reviews met inclusion criteria. The
      methodological quality of included studies have been very heterogeneous. Compared
      to usual cares, intervention is not associated with a statistically significant
      reduction of PI. DISCUSSION: A few and small available studies do not allow to
      ascertain a benefit from the intervention, if any. At the moment, the application
      of an individualized repositioning regimen seems a reasonable solution. Further
      researches are needed to confirm that a more frequent repositioning and a 30
      degrees  lateral decubitus intake help to prevent PI. It is also necessary to
      evaluate the economic impact, the acceptability and risks associated with the
      intervention. CONCLUSION: It is still unclear the role of repositioning regimen
      to prevent PI.

PMID- 29186649
TI  - [Unidimensional scales for dementia: a cross-sectional study in elderly Italian
      retirement houses residents].
AB  - BACKGROUND: The pain in instituzionalized elderly people with cognitive
      impairment is common. This symptom is severely under-reported and under-treated
      within this population. Evaluation of pain intensity is an essential component of
      pain assessment. Self-report approach to pain assessment is generally regarded as
      the gold standard of pain measurement in people with mild and moderate cognitive
      decay. The literature demonstrated more different unidimensional self-report
      scales but the conclusions of the studies suggested often the utilization of
      different scales. AIM: The goal of this study was to compare three different
      unidimensional pain assessment scales to be used with 84 instituzionalized
      elderly people with an average Mini-Mental State Examination score of 18. METHOD:
      This was a descriptive cross-sectional study. The pain assessment was carried out
      by administering the three scales Faces Pain Scale (FPS), Numeric Rating Scale
      (NRS), Verbal Rating Scale (VRS). RESULTS: The results showed that the prevalence
      of pain was 60-70%. All three pain intensity scales had good reliability and
      validity (p=0.0001); The compilation time of Faces Pain Scale most above than the
      other two scales (p=0.0001). CONCLUSION: The findings of this article support the
      implementation of these scales in operative protocols considering the compilation
      time and preferences of the patients.

PMID- 29186650
TI  - [Survey of secondary school students 18 years old or older about knowledge on
      risks to the fetus related to alcohol consumption during pregnancy].
AB  - INTRODUCTION:  Being not perceived as risky for health, alcohol consumption is
      socially accepted worldwide. Nevertheless, related risks for the fetus are
      relevant, even for occasional use. In Italy there is a high consumption of
      alcohol among young people and pregnant women, and an increasing number of
      children born with alcohol-related disorders. AIM: To investigate the knowledge
      on fetal alcohol-related disorders among students over 18 years of age in a
      regional capital in the North of Italy. METHODS: In May, 2015, a survey with an
      online, validated questionnaire was conducted on N=1321 students. RESULTS:  A
      total of N=246 valid questionnaires was obtained (18,6%). The 76,4% of students
      knew that drinking alcohol during pregnancy damages fetus, but only the 23,5%
      knew that this damages are permanent. Only the 43,5% knew that this damages are
      preventable; of them, the 77,6% stated that the only way to prevent them is
      abstention from alcohol consumption, though 30,1% answered that alcohol use is
      allowed without damage the fetus. Only the 17,5% answered to know Fetal Alcohol
      Spectrum Disorders. CONCLUSION:  The study showed satisfying knowledge on general
      aspects, but scarce on specific ones, and a limited awareness that only complete
      abstinence from alcohol when pregnant can prevent irreversible damages of the
      fetus. This results could help to program educational interventions for
      teenagers, carried out by nurses, pediatric nurses and other health professionals
      to increase their knowledge and prevent in utero exposure. Future studies could
      be aimed at identifying the most effective educational methods to do so.

PMID- 29186651
TI  - Lived experience of patients with glaucoma glaucoma: a phenomenological study.
AB  - INTRODUCTION: Glaucoma is often a misdiagnosed pathology and is one of the main
      causes of blindness in the world population.Glaucoma frequentlycauses limitations
      in theactivities of daily livingand changes the patient's quality of life. AIM:
      The purpose of our study is to describe the life experiences of subjects in
      southern Italy suffering from glaucoma. METHOD: Phenomenological study RESULTS:
      From the analysis of interviews six main themes emerged:(1) a profound change in
      lifestyle, (2) casual diagnosis,(3) independent research,(4) fear of
      blindness,(5) fear of being a burden to family, and (6) fear of familial
      pathology. Two additional themes appeared: the subjects felt lucky not to have a
      deadly disease and were uncertain about the future. CONCLUSION: The negative
      aspects prevail over any positive facets. A deep understanding of these
      experiences can help health care professionals to deliver correct holistic
      support.

PMID- 29186652
TI  - Combination of Obestatin and Bone Marrow Mesenchymal Stem Cells Prevents
      Aggravation of Endocrine Pancreatic Damage in Type II Diabetic Rats.
AB  - One of the new promising therapies in treatment of diabetes mellitus is
      mesenchymal stem cells (MSCs) which have an interesting therapeutic potentiality
      based on their paracrine effect and transdifferentiation potentiality. Also
      obestatin improves the generation of functional beta cells/islet-like cell
      clusters in vitro, suggesting implications for cell-based replacement therapy in
      diabetes. So the aim of this study was to evaluate the effect of combination of
      both MSCs and obestatin on an experimental model of type II diabetes mellitus
      (T2DM). Sixty male rats were divided into; group I (control group), group II
      (T2DM group) induced by administration of high fat diet (HFD) and injection of
      streptozotocin (STZ) in low dose, group III (T2DM treated with MSCs), group IV
      (T2DM treated with obestatin), group V (T2DM treated with MSCs and obestatin).
      Fasting blood glucose, C-peptide, insulin and lipid profile were measured. HOMA
      IR and HOMA-beta were calculated. Pancreatic expression of insulin, glucagon like
      peptide -1 (GLP-1) and pancreatic duodenal homeobox 1 (Pdx1) mRNA levels were
      measured. In addition pancreatic histological changes, insulin and Bax were
      analyzed by immunohistochemical examination of islets of Langerhans. Diabetic
      rats showed significant increase in HOMA-IR, serum glucose and lipid profile
      levels with significant decrease in insulin, HOMA-beta, GLP-1 and Pdx1 levels.
      MSCs and obestatin caused significant improvement in all parameters with more
      significant improvement in combined therapy. The protective effects afforded by
      MSCs and obestatin may derive from improvement of the metabolic profile,
      antiapoptosis and by increase in pancreatic GLP-1and Pdx1 gene expression.

PMID- 29186653
TI  - Mesenchymal Stem Cell Differentiation into Adipocytes Is Equally Induced by
      Insulin and Proinsulin In Vitro.
AB  - Background and Objectives: In advanced beta-cell dysfunction, proinsulin is
      increasingly replacing insulin as major component of the secretion product. It
      has been speculated that proinsulin has at least the same adipogenic potency than
      insulin, leading to an increased tendency of lipid tissue formation in patients
      with late stage beta-cell dysfunction. Methods and Results: Mesenchymal stem
      cells obtained from liposuction material were grown in differentiation media
      containing insulin (0.01 MUmol), proinsulin (0.01 MUmol) or insulin+proinsulin
      (each 0.005 MUmol). Cell culture supernatants were taken from these experiments
      and an untreated control at weeks 1, 2, and 3, and were stored at -80 degrees C
      until analysis. Cell differentiation was microscopically supervised and
      adiponectin concentrations were measured as marker for differentiation into
      mature lipid cells. This experiment was repeated three times. No growth of lipid
      cells and no change in adiponectin values was observed in the negative control
      group (after 7/14/12 days: 3.2+/-0.5/3.3+/-0.1/4.4+/-0.5 ng/ml/12 h). A
      continuous differentiation into mature adipocytes (also confirmed by Red-Oil
      staining) and a corresponding increase in adiponectin values was observed in the
      experiments with insulin (3.6+/-1.9/5.1+/-1.4/13.3+/-1.5 ng/ml/12 h; p<0.05 week
      1 vs. week 3) and proinsulin (3.3+/-1.2/3.5+/-0.3/12.2+/-1.2 ng/ml/12 h; p<0.05).
      Comparable effects were seen with the insulin/proinsulin combination.
      Conclusions: Proinsulin has the same adipogenic potential than insulin in vitro.
      Proinsulin has only 10~20% of the glucose-lowering effect of insulin. It can be
      speculated that the adipogenic potential of proinsulin may be a large contributor
      to the increased body weight problems in patients with type 2 diabetes and
      advanced beta-cell dysfunction.

PMID- 29186654
TI  - Treatment with Allogenic Mesenchymal Stromal Cells in a Murine Model of Systemic
      Lupus Erythematosus.
AB  - Objective: Pre-clinical and uncontrolled studies in patients with systemic lupus
      erythematosus (SLE) showed that mesenchymal stromal cells (MSCs) have a potential
      therapeutic role in refractory cases. The optimal therapeutic strategy in these
      patients remain to be elucidated. Our aim was to test the hypothesis that
      repeated administrations of 1*106/kg body weight of allogenic MSCs, that is a
      significantly lower dosage with respect to the fixed 1*106 MSC used in animal
      models, can be effective in improving the clinical course of a murine SLE model.
      Methods: Bone marrow derived MSCs were obtained from 12-week-old C57BL/6J mice.
      Seventy-five 8 weeks old female NZ mice were randomly assigned to receive via
      caudal vein the following alternative treatments: 1) single infusion of 106
      MSCs/kg body weight at 18 weeks of age (NZs18) or at at 22 weeks of age (NZs22);
      2) multiple monthly infusions of 106 MSCs/kg body weight starting at 18 weeks of
      age (NZM18) or at 22 weeks of age (NZM22); 3) saline infusions (NZc) Fifteen 8
      weeks old C57BL/6J mice (Envigo, Huntingdon, UK) were used as untreated controls
      (C). Weekly, body weight was recorded and twenty-four hour urines were collected
      by metabolic cages for each animal; proteinuria was detected by dipstick
      analysis. At sacrifice, peripheral blood samples were collected from mice and
      anti-dsDNA antibodies were detected by enzyme immunoassorbent assay (ELISA)
      method using commercial kits. At sacrifice, kidneys were analyzed for
      histopathology and immunohistochemical analysis for B220, CD4, MPO, CD4+Foxp3,
      F40/80 infiltration was performed. Results: Proteinuria occurrence was delayed
      NZS and NZM mice, no differences were observed in anti-dsDNA autoantibody titer
      among the groups at the different time-points; at 36 weeks, no significant
      differences were observed in term of nephritis scores. Inflammatory cells
      deposition (MPO and F4/80 positive cells) in NZM was significantly higher than in
      NZ and NZS. An overexpression of B lymphocytes (B220) was found in NZM while T
      regulatory cells (CD4+ Foxp3+ cells) were reduced in both NZS and NZM with
      respect to NZc. Conclusions: Overall, our study failed to show a positive effect
      of a treatment with murine MSCs in this model and, for some aspects, even
      deleterious results seem to be observed.

PMID- 29186655
TI  - Engineering Bifunctional Antibodies with Constant Region Fusion Architectures.
AB  - We report a method to generate bifunctional antibodies by grafting full-length
      proteins into constant region loops of a full-length antibody or an antigen
      binding fragment (Fab). The fusion proteins retain the antigen binding activity
      of the parent antibody but have an additional activity associated with the
      protein insert. The engineered antibodies have excellent in vitro activity,
      physiochemical properties, and stability. Among these, a Her2 * CD3 bispecific
      antibody (BsAb) was constructed by inserting an anti-Her2 single-chain variable
      fragment (ScFv) into an anti-CD3 Fab. This bispecific antibody efficiently
      induces targeted cell lysis in the presence of effector cells at as low as sub
      picomolar concentrations in vitro. Moreover, the Her2 * CD3 BsAb shows potent in
      vivo antitumor activity in mouse Her22+ and Her21+ xenograft models. These
      results demonstrate that insertion of a full-length protein into non-CDR loops of
      antibodies provides a feasible approach to generate multifunctional antibodies
      for therapeutic applications.

PMID- 29186656
TI  - Conformational Preference and Fluorescence Response of a C-Linked C8-Biphenyl
      Guanine Lesion in the NarI Mutational Hotspot: Evidence for Enhanced Syn Adduct
      Formation.
AB  - Aromatic chemical carcinogens can undergo enzymatic transformations to produce a
      range of electrophilic species that attach covalently to the C8-site of 2'
      deoxyguanosine (dG) to afford C8-dG adducts. The most studied C8-dG adducts are
      formed from arylamines and contain a N-linkage separating the dG from the C8-aryl
      moiety. Other carcinogenic species result in direct aryl ring attachment to the
      dG moiety, resulting in C-linked adducts. The resulting C-linked adducts have
      reduced conformational flexibility compared to the corresponding N-linked C8-dG
      adducts, which can alter their orientation in the DNA duplex. Described herein
      are structural studies of a fluorescent C-linked 4-fluorobiphenyl-dG (FBP-dG)
      that has been incorporated into the reiterated G3-postion of the 12-mer NarI
      sequence and those containing other 5'-flanking nucleobases. FBP-dG displays a
      strong preference for adopting a syn conformation in the fully paired NarI duplex
      to produce an intercalated structure that exhibits stacking interactions between
      the C-linked biphenyl and the flanking bases. FBP-dG is also shown to
      significantly stabilize the slippage mutagenic intermediate (SMI) duplex
      containing the lesion and 5'-flanking base within a 2-base bulge. FBP-dG exhibits
      fluorescence sensitivity to SMI duplex formation that can readily distinguish it
      from the fully paired duplex. Molecular dynamics simulations and optical
      spectroscopy for the NarI oligonucleotides containing the C-linked FBP-dG predict
      increased rigidity of the biphenyl in the syn conformation. The greater
      propensity to generate the promutagenic syn conformation for the C-linked FBP-dG
      adduct compared to the N-linked 4-aminobiphenyl-dG adduct (ABP-dG) suggests
      greater mutagenicity for the C-linked analogue. These results highlight the
      effect of the adduct linkage type on the conformational properties of adducted
      DNA. The turn-on emission response of FBP-dG in the SMI duplex may be a powerful
      tool for monitoring SMI formation in the NarI sequence upon synthesis with DNA
      polymerases.

PMID- 29186657
TI  - More Stable Template Localization for an Incremental Focal-Point Approach
      Implementation and Application to the Intramolecular Decomposition of Tris
      perfluoro-tert-butoxyalane.
AB  - We present a new implementation of the template localization for the fully
      automated and parallizable incremental method, which excludes failures of this
      important step within the domain-specific basis set approach and thus ensures a
      higher reliability of the scheme, preserving its very high accuracy. Furthermore,
      we combine our method with an efficient focal-point ansatz to reach the complete
      basis set limit and carefully assess this approach for the first time with regard
      to reaction energies. For a test set of 51 reactions the incremental focal-point
      method with a basis set of moderate size provides a very high accuracy with
      respect to the complete basis set limit. That way, we are finally able to apply
      the scheme as a benchmark method (e.g., for density functionals) in the context
      of a relevant chemical topic, the intramolecular decomposition of tris-perfluoro
      tert-butoxyalane (43 heavy atoms, 352 electrons).

PMID- 29186658
TI  - Stereoselectivity of Proline/Cyclobutane Amino Acid-Containing Peptide
      Organocatalysts for Asymmetric Aldol Additions: A Rationale.
AB  - Several alpha,beta,alpha- or alpha,gamma,alpha-tripeptides, consisting of a
      central cyclobutane beta- or gamma-amino acid being flanked by two d- or l
      proline residues, have been synthesized and tested as organocatalysts in
      asymmetric aldol additions. High yields and enantioselectivities have been
      achieved with alpha,gamma,alpha-tripeptides, being superior to peptides
      containing a cyclobutane beta-amino acid residue. This is probably due to their
      high rigidity, which hinders some of the peptide catalysts to adopt the proper
      active conformation. This reasoning correlates with the major conformation of the
      peptides in the ground state, as suggested by 1H NMR and computational
      calculations. The configuration of the aldol products is controlled by the
      proline chirality, and consequently, the R/S configuration of aldol products can
      be tuned by the use of either commercially available d- or l-proline. The
      enantioselectivity in the aldol reactions is reversed if the reactions are
      carried out in the presence of water or other protic solvents such as methanol.
      Spectroscopic and theoretical investigations revealed that this effect is not the
      consequence of conformational changes in the catalyst but rather caused by the
      participation of a water molecule in the rate determining transition state, in
      such a way that the preferential nucleophilic attack is oriented to the opposite
      enantiotopic aldehyde face.

PMID- 29186659
TI  - Operating Mechanisms of Mesoscopic Perovskite Solar Cells through Impedance
      Spectroscopy and J-V Modeling.
AB  - The performance of perovskite solar cell (PSC) is highly sensitive to deposition
      conditions, the substrate, humidity, and the efficiency of solvent extraction.
      However, the physical mechanism involved in the observed changes of efficiency
      with different deposition conditions has not been elucidated yet. In this work,
      PSCs were fabricated by the antisolvent deposition (AD) and recently proposed air
      extraction antisolvent (AAD) process. Impedance analysis and J-V curve fitting
      were used to analyze the photogeneration, charge transportation, recombination,
      and leakage properties of PSCs. It can be elucidated that the improvement in
      morphology of perovskite film promoted by AAD method leads to increase in light
      absorption, reduction in recombination sites, and interstitial defects, thus
      enhancing the short-circuit current density, open-circuit voltage, and fill
      factor. This study will open up doors for further improvement of device and help
      in understanding its physical mechanism and its relation to the deposition
      methods.

PMID- 29186660
TI  - Nanoparticle Stability in Axial InAs-InP Nanowire Heterostructures with
      Atomically Sharp Interfaces.
AB  - The possibility to expand the range of material combinations in defect-free
      heterostructures is one of the main motivations for the great interest in
      semiconductor nanowires. However, most axial nanowire heterostructures suffer
      from interface compositional gradients and kink formation, as a consequence of
      nanoparticle-nanowire interactions during the metal-assisted growth.
      Understanding such interactions and how they affect the growth mode is
      fundamental to achieve a full control over the morphology and the properties of
      nanowire heterostructures for device applications. Here we demonstrate that the
      sole parameter affecting the growth mode (straight or kinked) of InP segments on
      InAs nanowire stems by the Au-assisted method is the nanoparticle composition.
      Indeed, straight InAs-InP nanowire heterostructures are obtained only when the
      In/Au ratio in the nanoparticles is low, typically smaller than 1.5. For higher
      In content, the InP segments tend to kink. Tailoring the In/Au ratio by the
      precursor fluxes at a fixed growth temperature enables us to obtain straight and
      radius-uniform InAs-InP nanowire heterostructures (single and double) with
      atomically sharp interfaces. We present a model that is capable of describing all
      the experimentally observed phenomena: straight growth versus kinking, the
      stationary nanoparticle compositions in pure InAs and InAs-InP nanowires, the
      crystal phase trends, and the interfacial abruptness. By taking into account
      different nanowire/nanoparticle interfacial configurations (forming wetting or
      nonwetting monolayers in vertical or tapered geometry), our generalized model
      provides the conditions of nanoparticle stability and abrupt heterointerfaces for
      a rich variety of growth scenarios. Therefore, our results provide a powerful
      tool for obtaining high quality InAs-InP nanowire heterostructures with well
      controlled properties and can be extended to other material combinations based on
      the group V interchange.

PMID- 29186661
TI  - Sulfonyl-Containing Boronate Caps for Optimization of Biological Properties of
      99mTc(III) Radiotracers [99mTcCl(CDO)(CDOH)2B-R] (CDOH2 = Cyclohexanedione
      Dioxime).
AB  - In this study, different boronate caps were used to optimize biodistribution
      properties of radiotracers [99mTcCl(CDO)(CDOH)2B-R] (1, R = 3S; 2, R = 3SP; 3, R
      = 3MS; 4, R = 3DMS; 5, R = 3MSB; 6, R = 3MMS; 7, R = 3MSA; 8, R = 3DMSA; 9, R =
      4S; 10, R = 4MS; 11, R = 4MSB). Among the 11 new 99mTc radiotracers, 2 shows the
      most promising characteristics of an optimal heart imaging agent. Its initial
      heart uptake is close to that of 99mTc-Teboroxime, but its heart retention time
      is significantly longer. Its heart/liver, heart/lung, and heart/muscle ratios are
      also better than those of 99mTc-Teboroxime. The SPECT image quality with 2 in SD
      rats is better than that with 99mTc-Teboroxime. The high initial heart uptake,
      long heart retention, and high heart/background ratios make 2 an excellent SPECT
      radiotracer for MPI.

PMID- 29186663
TI  - The Plausibility of "Bronchiolotrauma".

PMID- 29186662
TI  - Ultrasmall-in-Nano Approach: Enabling the Translation of Metal Nanomaterials to
      Clinics.
AB  - Currently, nanomaterials are of widespread use in daily commercial products.
      However, the most-promising and potentially impacting application is in the
      medical field. In particular, nanosized noble metals hold the promise of shifting
      the current medical paradigms for the detection and therapy of neoplasms thanks
      to the: (i) localized surface plasmon resonances (LSPRs), (ii) high electron
      density, and (iii) suitability for straightforward development of all-in-one
      nanoplatforms. Nonetheless, there is still no clinically approved noble metal
      nanomaterial for cancer therapy and diagnostics. The clinical translation of
      noble metal nanoparticles (NPs) is mainly prevented by the issue of persistence
      in organism after the medical action. Such persistence increases the likelihood
      of toxicity and the interference with common medical diagnoses. Size reduction to
      ultrasmall nanoparticles (USNPs) is a suitable approach to promoting metal
      excretion by the renal pathway. However, most of the functionalities of NPs are
      lost or severely altered in USNPs, jeopardizing clinical applications. A ground
      breaking advance to jointly combine the appealing behaviors of NPs with metal
      excretion relies on the ultrasmall-in-nano approach for the design of all-in-one
      degradable nanoplatforms composed of USNPs. Such nanoarchitectures might lead to
      the delivery of a novel paradigm for nanotechnology, enabling the translation of
      noble metal nanomaterials to clinics to treat carcinomas in a less-invasive and
      more-efficient manner. This Review covers the recent progresses related to this
      exciting approach. The most-significant nanoarchitectures designed with the
      ultrasmall-in-nano approach are discussed, and perspectives on these
      nanoarchitectures are provided.

PMID- 29186664
TI  - The Fine Line between Success and Failure in Scleroderma Lung Fibrosis Trials.

PMID- 29186666
TI  - The Moderating Effect of Urban Versus Rural Residence on the Relationship Between
      Type of Birth Attendant and Early Initiation of Breastfeeding in Ghana.
AB  - BACKGROUND: Early initiation of breastfeeding increases the likelihood of longer
      duration of breastfeeding. Factors associated with breastfeeding include maternal
      sociodemographic, behavioral and health-related characteristics, infant health
      characteristics, and perinatal factors. Research aim: This study aimed to
      determine the association between type of birth attendant and early initiation of
      breastfeeding among women in Ghana. METHODS: A cross-sectional study was
      conducted using women ( N = 3,087) who participated in the 2014 Ghana Demographic
      and Health Survey. The main outcome of interest was early initiation of
      breastfeeding, defined as provision of mother's milk to the infant within 1 hr of
      birth. Chi-square tests and multivariable logistic regression modeling were
      performed. RESULTS: Breastfeeding was initiated within 1 hr of birth by 58.3% of
      women. In the multivariable model, there was a significant interaction between
      type of birth attendant and place of residence on early initiation of
      breastfeeding. For rural areas, compared with women who had a nurse or midwife as
      their birth attendant, the multivariable odds ratios [95% confidence intervals]
      for early initiation of breastfeeding were lower among women whose birth
      attendant was a relative or other, 0.20 [0.07, 0.55], p = .002; village health
      volunteer or traditional health practitioner, 0.21 [0.07, 0.62], p = .005; none,
      0.34 [0.12, 0.93], p = .035; community health officer, 0.42 [0.21, 0.85], p =
      .016; and doctor, 0.48 [0.24, 0.96], p = .037. For urban areas, no significant
      association was detected between type of birth attendant and early initiation of
      breastfeeding. CONCLUSION: Findings from the study highlight the need for
      focused, context-specific, early initiation of breastfeeding promotion and
      intervention, especially for women and their birth attendants in rural areas.

PMID- 29186665
TI  - Discovery and Characterization of Chemical Compounds That Inhibit the Function of
      Aspartyl-tRNA Synthetase from Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa, an opportunistic pathogen, is highly susceptible to
      developing resistance to multiple antibiotics. The gene encoding aspartyl-tRNA
      synthetase (AspRS) from P. aeruginosa was cloned and the resulting protein
      characterized. AspRS was kinetically evaluated, and the KM values for aspartic
      acid, ATP, and tRNA were 170, 495, and 0.5 MUM, respectively. AspRS was developed
      into a screening platform using scintillation proximity assay (SPA) technology
      and used to screen 1690 chemical compounds, resulting in the identification of
      two inhibitory compounds, BT02A02 and BT02C05. The minimum inhibitory
      concentrations (MICs) were determined against nine clinically relevant bacterial
      strains, including efflux pump mutant and hypersensitive strains of P.
      aeruginosa. The compounds displayed broad-spectrum antibacterial activity and
      inhibited growth of the efflux and hypersensitive strains with MICs of 16 MUg/mL.
      Growth of wild-type strains were unaffected, indicating that efflux was likely
      responsible for this lack of activity. BT02A02 did not inhibit growth of human
      cell cultures at any concentration. However, BT02C05 did inhibit human cell
      cultures with a cytotoxicity concentration (CC50) of 61.6 MUg/mL. The compounds
      did not compete with either aspartic acid or ATP for binding AspRS, indicating
      that the mechanism of action of the compound occurs outside the active site of
      aminoacylation.

PMID- 29186668
TI  - Emulation of Colonic Oxygen Gradients in a Microdevice.
AB  - Gut-on-a-chip in vitro modeling is an emerging field, as the human gut epithelium
      and gut microbiome have been recently identified as novel drug targets for a wide
      variety of diseases. Realistic in vitro gut models require a variety of precise
      environmental cues, such as chemical and gas gradients, in combination with
      substrates like mucus that support the growth of microbial communities. This
      technical brief describes a microfluidic architecture capable of developing a
      physiologically relevant oxygen gradient that emulates the oxygen profile
      proximal to the epithelial inner lining of the human colon. The device generates
      stable and repeatable defined oxygen gradients from 0% to 4 % partial pressure O2
      over a length scale of hundreds of microns, and was applied to study the effects
      of oxygenation on the structure of native mucus that lines the colon wall. Using
      simulation as a design tool for hybrid gas-liquid microfluidic devices enables on
      chip creation of defined, physiologically oxygen gradients. These microfluidic
      architectures have powerful potential applications for gut physiology, including
      providing optimal oxygenation conditions for the culture of mammalian epithelial
      cells in the gut lining, as well as creating a realistic mimic of the oxygen
      gradient found in the intestinal lumen for complex microbiome cultures.

PMID- 29186669
TI  - High-Capacity Redox Polymer Electrodes: Applications in Molecular and Cellular
      Processing.
AB  - We present methods to fabricate high-capacity redox electrodes using thick
      membrane or fiber casting of conjugated polymer solutions. Unlike common solution
      casting or printing methods used in current organic electronics, the presented
      techniques enable production of PEDOT:PSS electrodes with high charge capacity
      and the capability to operate under applied voltages greater than 100 V without
      electrochemical overoxidation. The electrodes are shown integrated into several
      electrokinetic components commonly used in automated bioprocess or bioassay
      workflows, including electrophoretic DNA separation and extraction, cellular
      electroporation/lysis, and electroosmotic pumping. Unlike current metal
      electrodes used in these applications, the high-capacity polymer electrodes are
      shown to function without electrolysis of solvent (i.e., without production of
      excess H+, OH-, and H2O2 by-products). In addition, each component fabricated
      using the electrodes is shown to have superior capabilities compared with those
      fabricated with common metal electrodes. These innovations in electrokinetics
      include a low-voltage/high-pressure electroosmotic pump, and a "flow battery" (in
      which electrochemical discharge is used to generate electroosmotic flow in the
      absence of an applied potential). The novel electrodes (and electrokinetic
      demonstrations) enable new applications of organic electronics within the
      biology, health care, and pharmaceutical fields.

PMID- 29186670
TI  - Changes in extreme events and the potential impacts on human health.
AB  - : Extreme weather and climate-related events affect human health by causing
      death, injury, and illness, as well as having large socioeconomic impacts.
      Climate change has caused changes in extreme event frequency, intensity, and
      geographic distribution, and will continue to be a driver for change in the
      future. Some of these events include heat waves, droughts, wildfires, dust
      storms, flooding rains, coastal flooding, storm surges, and hurricanes. The
      pathways connecting extreme events to health outcomes and economic losses can be
      diverse and complex. The difficulty in predicting these relationships comes from
      the local societal and environmental factors that affect disease burden. More
      information is needed about the impacts of climate change on public health and
      economies to effectively plan for and adapt to climate change. This paper
      describes some of the ways extreme events are changing and provides examples of
      the potential impacts on human health and infrastructure. It also identifies key
      research gaps to be addressed to improve the resilience of public health to
      extreme events in the future. IMPLICATIONS: Extreme weather and climate events
      affect human health by causing death, injury, and illness, as well as having
      large socioeconomic impacts. Climate change has caused changes in extreme event
      frequency, intensity, and geographic distribution, and will continue to be a
      driver for change in the future. Some of these events include heat waves,
      droughts, wildfires, flooding rains, coastal flooding, surges, and hurricanes.
      The pathways connecting extreme events to health outcomes and economic losses can
      be diverse and complex. The difficulty in predicting these relationships comes
      from the local societal and environmental factors that affect disease burden.

PMID- 29186671
TI  - Reply to Borges: The Plausibility of "Bronchiolotrauma".

PMID- 29186673
TI  - Disparate Postsynaptic Induction Mechanisms Ultimately Converge to Drive the
      Retrograde Enhancement of Presynaptic Efficacy.
AB  - Retrograde signaling systems are fundamental modes of communication synapses
      utilize to dynamically and adaptively modulate activity. However, the inductive
      mechanisms that gate retrograde communication in the postsynaptic compartment
      remain enigmatic. We have investigated retrograde signaling at the Drosophila
      neuromuscular junction, where three seemingly disparate perturbations to the
      postsynaptic cell trigger a similar enhancement in presynaptic neurotransmitter
      release. We show that the same presynaptic genetic machinery and enhancements in
      active zone structure are utilized by each inductive pathway. However, all three
      induction mechanisms differ in temporal, translational, and CamKII activity
      requirements to initiate retrograde signaling in the postsynaptic cell.
      Intriguingly, pharmacological blockade of postsynaptic glutamate receptors, and
      not calcium influx through these receptors, is necessary and sufficient to induce
      rapid retrograde homeostatic signaling through CamKII. Thus, three distinct
      induction mechanisms converge on the same retrograde signaling system to drive
      the homeostatic strengthening of presynaptic neurotransmitter release.

PMID- 29186674
TI  - Cellular and Molecular Anatomy of the Human Neuromuscular Junction.
AB  - The neuromuscular junction (NMJ) plays a fundamental role in transferring
      information from lower motor neuron to skeletal muscle to generate movement. It
      is also an experimentally accessible model synapse routinely studied in animal
      models to explore fundamental aspects of synaptic form and function. Here, we
      combined morphological techniques, super-resolution imaging, and proteomic
      profiling to reveal the detailed cellular and molecular architecture of the human
      NMJ. Human NMJs were significantly smaller, less complex, and more fragmented
      than mouse NMJs. In contrast to mice, human NMJs were also remarkably stable
      across the entire adult lifespan, showing no signs of age-related degeneration or
      remodeling. Super-resolution imaging and proteomic profiling revealed distinctive
      distribution of active zone proteins and differential expression of core synaptic
      proteins and molecular pathways at the human NMJ. Taken together, these findings
      reveal human-specific cellular and molecular features of the NMJ that distinguish
      them from comparable synapses in other mammalian species.

PMID- 29186675
TI  - Inactivation of Mechanically Activated Piezo1 Ion Channels Is Determined by the C
      Terminal Extracellular Domain and the Inner Pore Helix.
AB  - Piezo proteins form mechanically activated ion channels that are responsible for
      our sense of light touch, proprioception, and vascular blood flow. Upon
      activation by mechanical stimuli, Piezo channels rapidly inactivate in a voltage
      dependent manner through an unknown mechanism. Inactivation of Piezo channels is
      physiologically important, as it modulates overall mechanical sensitivity, gives
      rise to frequency filtering of repetitive mechanical stimuli, and is itself the
      target of numerous human disease-related channelopathies that are not well
      understood mechanistically. Here, we identify the globular C-terminal
      extracellular domain as a structure that is sufficient to confer the time course
      of inactivation and a single positively charged lysine residue at the adjacent
      inner pore helix as being required for its voltage dependence. Our results are
      consistent with a mechanism for inactivation that is mediated through voltage
      dependent conformations of the inner pore helix and allosteric coupling with the
      C-terminal extracellular domain.

PMID- 29186677
TI  - The Methyltransferase Setd8 Is Essential for Erythroblast Survival and
      Maturation.
AB  - Erythropoiesis is a highly regulated process that generates enucleate red blood
      cells from committed erythroid progenitors. Chromatin condensation culminating in
      enucleation is a defining feature of this process. Setd8 is the sole enzyme that
      can mono-methylate histone H4, lysine 20 and is highly expressed in erythroblasts
      compared to most other cell types. Erythroid Setd8 deletion results in embryonic
      lethality from severe anemia due to impaired erythroblast survival and
      proliferation. Setd8 protein levels are also uniquely regulated in erythroblasts,
      suggesting a cell-type-specific role for Setd8 during terminal maturation.
      Consistent with this hypothesis, Setd8 Delta/Delta erythroblasts have profound
      defects in transcriptional repression, chromatin condensation, and
      heterochromatin accumulation. Together, these results suggest that Setd8, used by
      most cells to promote mitotic chromatin condensation, is an essential aspect of
      the transcriptional repression and chromatin condensation that are hallmarks of
      terminal erythroid maturation.

PMID- 29186676
TI  - The Circadian Clock Regulates Adipogenesis by a Per3 Crosstalk Pathway to Klf15.
AB  - The generation of new adipocytes from precursor cells (adipogenesis) has
      implications for systemic metabolism and is a commonly used model for studying
      the process of cell differentiation in vitro. Previous studies from us and others
      suggested that the peripheral circadian clock can influence adipogenesis in
      vitro, but the mechanisms driving this activity and the relevance for
      adipogenesis in vivo are unknown. Here we reveal that mouse adipocyte precursor
      cells (APCs) contain a circadian clock that oscillates in vivo. We expose context
      specific features of the clock in APCs: expression of the canonical core clock
      component Per1 does not significantly oscillate, whereas the lesser-understood
      paralog Per3 has a prominent rhythm. We discovered that deletion of Per3 promotes
      adipogenesis in vivo by a clock output pathway in which PER3 and BMAL1 directly
      regulate Klf15 expression. These findings demonstrate that Per3 has a major role
      in the APC clock and regulates adipogenesis in vivo.

PMID- 29186678
TI  - Hyperglycemia Impairs Neutrophil Mobilization Leading to Enhanced Metastatic
      Seeding.
AB  - Preexisting diabetes is a risk factor for the development of multiple types of
      cancer. Additionally, diabetic patients face a poorer prognosis when diagnosed
      with cancer. To gain insight into the effects of hyperglycemia, a hallmark of
      diabetes, on tumor growth and metastatic progression, we combined mouse models of
      cancer and hyperglycemia. We show that while hyperglycemia attenuates primary
      tumor growth, it concomitantly increases metastatic seeding in a distant organ.
      We further show that the increase in metastatic seeding is due to impaired
      secretion of granulocyte colony-stimulating factor (G-CSF) and impaired
      neutrophil mobilization. Normalizing blood glucose levels using insulin rescues
      neutrophil recruitment and tumor growth and concomitantly reduces metastatic
      seeding. These results provide links among hyperglycemia-induced changes in
      neutrophil mobilization, primary tumor growth, and metastatic progression.
      Furthermore, our observations highlight the importance of normalizing blood
      glucose levels in hyperglycemic cancer patients.

PMID- 29186679
TI  - Functional Specialization of the Primate Frontal Lobe during Cognitive Control of
      Vocalizations.
AB  - Cognitive vocal control is indispensable for human language. Frontal lobe areas
      are involved in initiating purposeful vocalizations, but their functions remain
      elusive. We explored the respective roles of frontal lobe areas in initiating
      volitional vocalizations. Macaques were trained to vocalize in response to visual
      cues. Recordings from the ventrolateral prefrontal cortex (vlPFC), the anterior
      cingulate cortex (ACC), and the pre-supplementary motor area (preSMA) revealed
      single-neuron and population activity differences. Pre-vocal activity appeared
      first after the go cue in vlPFC, showing onset activity that was tightly linked
      to vocal reaction times. However, pre-vocal ACC onset activity was not indicative
      of call timing; instead, ramping activity reaching threshold values betrayed call
      onset. Neurons in preSMA showed weakest correlation with volitional call
      initiation and timing. These results suggest that vlPFC encodes the decision to
      produce volitional calls, whereas downstream ACC represents a motivational
      preparatory signal, followed by a general motor priming signal in preSMA.

PMID- 29186680
TI  - Astrocytic l-Lactate Signaling Facilitates Amygdala-Anterior Cingulate Cortex
      Synchrony and Decision Making in Rats.
AB  - Human brain imaging studies have revealed the anterior cingulate cortex (ACC) as
      a key brain region for mediating visceral-pain-cognitive interactions. Recently,
      we characterized impairments of long-term potentiation and spike-field coherence
      in the basolateral amygdala (BLA)-ACC network in association with a decision
      making deficit in rats with visceral hypersensitivity (VH). Now, by combining
      integrative neurobiological approaches, we show that ACC-reactive astrogliosis
      and activity-dependent impairment of lactate release occur in VH rats. Exogenous
      lactate supply rescues chronic-visceral-pain-caused impairments of ACC phase
      locking and decision making, which can be mimicked by optogenetic activation of
      ACC astrocytes. Large-scale electrophysiological recordings in free-moving
      animals during a decision-making task indicate that optogenetic astrocytic
      activation improves decision-making performance and engages ACC phase locking and
      BLA-to-ACC information flow. Collectively, these observations support the idea of
      an "astrocyte-neuron l-lactate shuttle" and suggest that targeting astrocytes may
      help with cognitive dysfunctions under chronic visceral pain.

PMID- 29186682
TI  - Control of Gene Expression in Senescence through Transcriptional Read-Through of
      Convergent Protein-Coding Genes.
AB  - Antisense RNAs are non-coding RNAs that can regulate their corresponding sense
      RNAs and are generally produced from specific promoters. We uncover here a family
      of antisense RNAs, named START RNAs, produced during cellular senescence by
      transcriptional read-through at convergent protein-coding genes. Importantly,
      START RNAs repress the expression of their corresponding sense RNAs. In
      proliferative cells, we found that the Pol II elongation rate is limited
      downstream of TTS at START loci, allowing transcription termination to occur
      before Pol II reaches the convergent genes, thus preventing antisense RNA
      production and interference with the expression of the convergent genes. START
      RNAs are repressed by H2A.Z histone variant, whose local occupancy decreases in
      senescence. Our results thus uncover a mechanism of gene expression regulation
      relying on read-through antisense transcript production at convergent genes,
      underlining the functional importance of chromatin regulation in the control of
      RNA pol II elongation rate at intergenic regions.

PMID- 29186681
TI  - Gamma Oscillations in Rat Hippocampal Subregions Dentate Gyrus, CA3, CA1, and
      Subiculum Underlie Associative Memory Encoding.
AB  - Neuronal oscillations in the rat hippocampus relate to both memory and
      locomotion, raising the question of how these cognitive and behavioral correlates
      interact to determine the oscillatory network state of this region. Here, rats
      freely locomoted while performing an object-location task designed to test
      hippocampus-dependent spatial associative memory. Rhythmic activity in theta,
      beta, slow gamma, and fast gamma frequency ranges were observed in both action
      potentials and local field potentials (LFPs) across four main hippocampal
      subregions. Several patterns of LFP oscillations corresponded to overt behavior
      (e.g., increased dentate gyrus-CA3 beta coherence during stationary moments and
      CA1-subiculum theta coherence during locomotion). In comparison, slow gamma (~40
      Hz) oscillations throughout the hippocampus related most specifically to object
      location associative memory encoding rather than overt behavior. The results help
      to untangle how hippocampal oscillations relate to both memory and motion and
      single out slow gamma oscillations as a distinguishing correlate of spatial
      associative memory.

PMID- 29186683
TI  - TRIM48 Promotes ASK1 Activation and Cell Death through Ubiquitination-Dependent
      Degradation of the ASK1-Negative Regulator PRMT1.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is an oxidative stress-responsive
      kinase that is regulated by various interacting molecules and post-translational
      modifications. However, how these molecules and modifications cooperatively
      regulate ASK1 activity remains largely unknown. Here, we showed that tripartite
      motif 48 (TRIM48) orchestrates the regulation of oxidative stress-induced ASK1
      activation. A pull-down screen identified a TRIM48-interacting partner, protein
      arginine methyltransferase 1 (PRMT1), which negatively regulates ASK1 activation
      by enhancing its interaction with thioredoxin (Trx), another ASK1-negative
      regulator. TRIM48 facilitates ASK1 activation by promoting K48-linked
      polyubiquitination and degradation of PRMT1. TRIM48 knockdown suppressed
      oxidative stress-induced ASK1 activation and cell death, whereas forced
      expression promoted cancer cell death in mouse xenograft model. These results
      indicate that TRIM48 facilitates oxidative stress-induced ASK1 activation and
      cell death through ubiquitination-dependent degradation of PRMT1. This study
      provides a cell death mechanism fine-tuned by the crosstalk between enzymes that
      engage various types of post-translational modifications.

PMID- 29186685
TI  - Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis
      Promotes Recruitment of Tumor-Associated Macrophages.
AB  - C-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation,
      progression, and metastasis. Although CCL2 expression has been found to be
      dependent on the nuclear factor (NF)-kappaB signaling pathway, the regulation of
      CCL2 production in tumor cells has remained unclear. We have identified a
      noncanonical pathway for regulation of CCL2 production that is mediated by
      mammalian target of rapamycin complex 1 (mTORC1) but independent of NF-kappaB.
      Multiple phosphoproteomics approaches identified the transcription factor
      forkhead box K1 (FOXK1) as a downstream target of mTORC1. Activation of mTORC1
      induces dephosphorylation of FOXK1, resulting in transactivation of the CCL2
      gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2
      production as well as the accumulation of tumor-associated monocytes-macrophages
      and tumor progression in mice. Our results suggest that FOXK1 directly links
      mTORC1 signaling and CCL2 expression in a manner independent of NF-kappaB and
      that CCL2 produced by this pathway contributes to tumor progression.

PMID- 29186684
TI  - Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk
      Analyses in Patient-Derived Xenografts.
AB  - Preclinical models based on patient-derived xenografts have remarkable
      specificity in distinguishing transformed human tumor cells from non-transformed
      murine stromal cells computationally. We obtained 29 pancreatic ductal
      adenocarcinoma (PDAC) xenografts from either resectable or non-resectable
      patients (surgery and endoscopic ultrasound-guided fine-needle aspirate,
      respectively). Extensive multiomic profiling revealed two subtypes with distinct
      clinical outcomes. These subtypes uncovered specific alterations in DNA
      methylation and transcription as well as in signaling pathways involved in tumor
      stromal cross-talk. The analysis of these pathways indicates therapeutic
      opportunities for targeting both compartments and their interactions. In
      particular, we show that inhibiting NPC1L1 with Ezetimibe, a clinically available
      drug, might be an efficient approach for treating pancreatic cancers. These
      findings uncover the complex and diverse interplay between PDAC tumors and the
      stroma and demonstrate the pivotal role of xenografts for drug discovery and
      relevance to PDAC.

PMID- 29186686
TI  - Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway
      Inflammation.
AB  - Sex hormones regulate many autoimmune and inflammatory diseases, including
      asthma. As adults, asthma prevalence is 2-fold greater in women compared to men.
      The number of group 2 innate lymphoid cells (ILC2) is increased in patients with
      asthma, and we investigate how testosterone attenuates ILC2 function. In patients
      with moderate to severe asthma, we determine that women have an increased number
      of circulating ILC2 compared to men. ILC2 from adult female mice have increased
      IL-2-mediated ILC2 proliferation versus ILC2 from adult male mice, as well as pre
      pubescent females and males. Further, 5alpha-dihydrotestosterone, a hormone
      downstream of testosterone, decreases lung ILC2 numbers and IL-5 and IL-13
      expression from ILC2. In vivo, testosterone attenuated Alternaria-extract-induced
      IL-5+ and IL-13+ ILC2 numbers and lung eosinophils by intrinsically decreasing
      lung ILC2 numbers, as well as by decreasing expression of IL-33 and thymic
      stromal lymphopoietin (TSLP), ILC2-stimulating cytokines. Collectively, these
      findings provide a foundational understanding of sexual dimorphism in ILC2
      function.

PMID- 29186687
TI  - Perivascular Fibroblasts of the Developing Spleen Act as LTalpha1beta2-Dependent
      Precursors of Both T and B Zone Organizer Cells.
AB  - T and B cell compartmentalization is a hallmark of secondary lymphoid organs and
      is maintained by chemokine-expressing stromal cells. How this stromal cell
      network initially develops and differentiates into two distinct subsets is poorly
      known, especially for the splenic white pulp (WP). Here, we show that
      perivascular fibroblast precursors are triggered by LTalpha1beta2 signals to
      expand, express CCL19/21, and then differentiate into two functionally distinct
      fibroblast subsets responsible for B and T cell clustering and WP
      compartmentalization. Failure to express or sense CCL19 leads to impaired T zone
      development, while lack of B cells or LTalpha1beta2 leads to an earlier and
      stronger impairment in WP development. We therefore propose that WP development
      proceeds in multiple steps, with LTalpha1beta2+ B cells acting as major inducer
      cells driving the expansion and gradual differentiation of perivascular
      fibroblasts into T and B zone organizer cells.

PMID- 29186689
TI  - Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral
      Infection.
AB  - NK cells can reduce anti-viral T cell immunity during chronic viral infections,
      including infection with the lymphocytic choriomeningitis virus (LCMV). However,
      regulating factors that maintain the equilibrium between productive T cell and NK
      cell immunity are poorly understood. Here, we show that a large viral load
      resulted in inhibition of NK cell activation, which correlated with increased
      expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was
      predominantly upregulated on B cells following LCMV infection, and this
      upregulation was dependent on type I interferons. Absence of Qa-1b resulted in
      increased NK cell-mediated regulation of anti-viral T cells following viral
      infection. Consequently, anti-viral T cell immunity was reduced in Qa-1b- and
      NKG2A-deficient mice, resulting in increased viral replication and
      immunopathology. NK cell depletion restored anti-viral immunity and virus control
      in the absence of Qa-1b. Taken together, our findings indicate that lymphocytes
      limit NK cell activity during viral infection in order to promote anti-viral T
      cell immunity.

PMID- 29186688
TI  - Receptor Activator of NF-kappaB Orchestrates Activation of Antiviral Memory CD8 T
      Cells in the Spleen Marginal Zone.
AB  - The spleen plays an important role in protective immunity to bloodborne
      pathogens. Macrophages and dendritic cells (DCs) in the spleen marginal zone
      capture microbial antigens to trigger adaptive immune responses. Marginal zone
      macrophages (MZMs) can also act as a replicative niche for intracellular
      pathogens, providing a platform for mounting the immune response. Here, we
      describe a role for RANK in the coordinated function of antigen-presenting cells
      in the spleen marginal zone and triggering anti-viral immunity. Targeted deletion
      of RANK results in the selective loss of CD169+ MZMs, which provide a niche for
      viral replication, while RANK signaling in DCs promotes the recruitment and
      activation of anti-viral memory CD8 T cells. These studies reveal a role for the
      RANKL/RANK signaling axis in the orchestration of protective immune responses in
      the spleen marginal zone that has important implications for the host response to
      viral infection and induction of acquired immunity.

PMID- 29186690
TI  - Growth of B Cell Receptor Microclusters Is Regulated by PIP2 and PIP3 Equilibrium
      and Dock2 Recruitment and Activation.
AB  - The growth of B cell receptor (BCR) microclusters upon antigen stimulation drives
      B cell activation. Here, we show that PI3K-mediated PIP3 production is required
      for the growth of BCR microclusters. This growth is likely inhibited by PTEN and
      dependent on its plasma membrane binding and lipid phosphatase activities.
      Mechanistically, we find that PIP3-dependent recruitment and activation of a
      guanine nucleotide exchange factor, Dock2, is required for the sustained growth
      of BCR microclusters through remodeling of the F-actin cytoskeleton. As a
      consequence, Dock2 deficiency significantly disrupts the structure of the B cell
      immunological synapse. Finally, we find that primary B cells from systemic lupus
      erythematosus (SLE) patients exhibit more prominent BCR and PI3K microclusters
      than B cells from healthy controls. These results demonstrate the importance of a
      PI3K- and PTEN-governed PIP2 and PIP3 equilibrium in regulating the activation of
      B cells through Dock2-controlled growth of BCR microclusters.

PMID- 29186691
TI  - Immunoproteasomes Control the Homeostasis of Medullary Thymic Epithelial Cells by
      Alleviating Proteotoxic Stress.
AB  - The sole nonredundant role of the thymic medulla is to induce central tolerance,
      a vital process that depends on promiscuous gene expression (pGE), a unique
      feature of medullary thymic epithelial cells (mTECs). Although pGE enhances
      transcription of >3,000 genes in mTECs, its impact on the regulation of protein
      homeostasis remains unexplored. Here, we report that, because of pGE, mature
      mTECs synthesize substantially more proteins than other cell types and are
      exquisitely sensitive to loss of immunoproteasomes (IPs). Indeed, IP deficiency
      causes proteotoxic stress in mTECs and leads to exhaustion of postnatal mTEC
      progenitors. Moreover, IP-deficient mice show accelerated thymic involution,
      which is characterized by a selective loss of mTECs and multiorgan autoimmune
      manifestations. We conclude that pGE, the quintessential feature of mTECs, is a
      major burden for the maintenance of proteostasis, which is alleviated by the
      constitutive expression of IPs in mTECs.

PMID- 29186692
TI  - Quiescence Exit of Tert+ Stem Cells by Wnt/beta-Catenin Is Indispensable for
      Intestinal Regeneration.
AB  - Fine control of stem cell maintenance and activation is crucial for tissue
      homeostasis and regeneration. However, the mechanism of quiescence exit of Tert+
      intestinal stem cells (ISCs) remains unknown. Employing a Tert knockin
      (TertTCE/+) mouse model, we found that Tert+ cells are long-term label-retaining
      self-renewing cells, which are partially distinguished from the previously
      identified +4 ISCs. Tert+ cells become mitotic upon irradiation (IR) injury.
      Conditional ablation of Tert+ cells impairs IR-induced intestinal regeneration
      but not intestinal homeostasis. Upon IR injury, Wnt signaling is specifically
      activated in Tert+ cells via the ROS-HIFs-transactivated Wnt2b signaling axis.
      Importantly, conditional knockout of beta-catenin/Ctnnb1 in Tert+ cells
      undermines IR-induced quiescence exit of Tert+ cells, which subsequently impedes
      intestinal regeneration. Our results that Wnt-signaling-induced activation of
      Tert+ ISCs is indispensable for intestinal regeneration unveil the underlying
      mechanism for how Tert+ stem cells undergo quiescence exit upon tissue injury.

PMID- 29186693
TI  - Osteocyte-Intrinsic TGF-beta Signaling Regulates Bone Quality through
      Perilacunar/Canalicular Remodeling.
AB  - Poor bone quality contributes to bone fragility in diabetes, aging, and
      osteogenesis imperfecta. However, the mechanisms controlling bone quality are not
      well understood, contributing to the current lack of strategies to diagnose or
      treat bone quality deficits. Transforming growth factor beta (TGF-beta) signaling
      is a crucial mechanism known to regulate the material quality of bone, but its
      cellular target in this regulation is unknown. Studies showing that osteocytes
      directly remodel their perilacunar/canalicular matrix led us to hypothesize that
      TGF-beta controls bone quality through perilacunar/canalicular remodeling (PLR).
      Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-beta
      signaling (TbetaRIIocy-/-), we show that TGF-beta regulates PLR in a cell
      intrinsic manner to control bone quality. Altogether, this study emphasizes that
      osteocytes are key in executing the biological control of bone quality through
      PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone
      homeostasis and fragility.

PMID- 29186696
TI  - A Highly Sensitive FRET Biosensor for AMPK Exhibits Heterogeneous AMPK Responses
      among Cells and Organs.
AB  - AMP-activated protein kinase (AMPK), a master regulator of cellular metabolism,
      is a potential target for type 2 diabetes. Although extensive in vitro studies
      have revealed the complex regulation of AMPK, much remains unknown about the
      regulation in vivo. We therefore developed transgenic mice expressing a highly
      sensitive fluorescence resonance energy transfer (FRET)-based biosensor for AMPK,
      called AMPKAR-EV. AMPKAR-EV allowed us to readily examine the role of LKB1, a
      canonical stimulator of AMPK, in drug-induced activation and inactivation of AMPK
      in vitro. In transgenic mice expressing AMPKAR-EV, the AMP analog AICAR activated
      AMPK in muscle. In contrast, the antidiabetic drug metformin activated AMPK in
      liver, highlighting the organ-specific action of AMPK stimulators. Moreover, we
      found that AMPK was activated primarily in fast-twitch muscle fibers after
      tetanic contraction and exercise. These observations suggest that the AMPKAR-EV
      mouse will pave a way to understanding the heterogeneous responses of AMPK among
      cell types in vivo.

PMID- 29186697
TI  - A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan
      Extending Compounds.
AB  - Progress in aging research is constrained by the time requirement of measuring
      lifespans. Even the most rapid model for eukaryotic aging, the replicative
      lifespan of Saccharomyces cerevisiae, is technically limited to only several
      lifespan measurements each day. Here we report a 384-well plate-based technique
      to measure replicative lifespan, termed High-Life. Using the High-Life technique,
      a single researcher can compare lifespan for more than 1,000 conditions per day.
      We validated the technique with long-lived mutant strains and the lifespan
      extending compound ibuprofen. We also applied this technique to screen a small
      compound library for lifespan extension. Two hits, terreic acid and mycophenolic
      acid, were validated on our single-cell replicator device and found to extend
      mean replicative lifespan by 15% and 20%, respectively. Together, we report a
      technique for high-throughput lifespan measurement, and we identify two lifespan
      extending compounds. Our technique could be used to efficiently drive early-stage
      discovery of pro-longevity therapeutics.

PMID- 29186698
TI  - Effect of atorvastatin on behavioral alterations and neuroinflammation during
      epileptogenesis.
AB  - Temporal lobe epilepsy (TLE) is the most frequent and medically refractory type
      of epilepsy in humans. In addition to seizures, patients with TLE suffer from
      behavioral alterations and cognitive deficits. Poststatus epilepticus model of
      TLE induced by pilocarpine in rodents has enhanced the understanding of the
      processes leading to epilepsy and thus, of potential targets for
      antiepileptogenic therapies. Clinical and experimental evidence suggests that
      inflammatory processes in the brain may critically contribute to epileptogenesis.
      Statins are inhibitors of cholesterol synthesis, and present pleiotropic effects
      that include antiinflammatory properties. We aimed the present study to test the
      hypothesis that atorvastatin prevents behavioral alterations and proinflammatory
      state in the early period after pilocarpine-induced status epilepticus. Male and
      female C57BL/6 mice were subjected to status epilepticus induced by pilocarpine
      and treated with atorvastatin (10 or 100mg/kg) for 14days. Atorvastatin slightly
      improved the performance of mice in the open-field and object recognition tests.
      In addition, atorvastatin dose-dependently decreased basal and status epilepticus
      induced levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha), and interferon-gamma (INF-gamma) and increased
      interleukin-10 (IL-10) levels in the hippocampus and cerebral cortex. The
      antiinflammatory effects of atorvastatin were qualitatively identical in both
      sexes. Altogether, these findings extend the range of beneficial actions of
      atorvastatin and indicate that its antiinflammatory effects may be useful after
      an epileptogenic insult.

PMID- 29186699
TI  - Seizure-induced activation of the HPA axis increases seizure frequency and
      comorbid depression-like behaviors.
AB  - Our laboratory recently demonstrated that seizures activate the hypothalamic
      pituitary-adrenal (HPA) axis, increasing circulating levels of corticosterone
      (O'Toole et al., 2013). Given the well-established proconvulsant actions of
      corticosterone, we hypothesized that seizure-induced activation of the HPA axis
      may contribute to future seizure susceptibility. Further, since hypercortisolism
      is associated with depression, we propose that seizure-induced activation of the
      HPA axis may contribute to comorbid depression and epilepsy. To test this
      hypothesis, we generated mice lacking the GABAA receptor (GABAAR) delta subunit
      specifically in corticotropin-releasing hormone (CRH) neurons (Gabrd/Crh mice),
      which exhibit hyporeactivity of the HPA axis (Lee et al., 2014). Gabrd/Crh mice
      exhibit blunted seizure-induced elevations in corticosterone, establishing a
      useful tool to investigate the contribution of HPA axis dysfunction on epilepsy
      and associated comorbidities. Interestingly, Gabrd/Crh mice exhibit decreased
      acute seizure susceptibility following kainic acid (KA) administration.
      Furthermore, chronically epileptic Gabrd/Crh mice exhibit a decrease in both
      spontaneous seizure frequency and depression-like behaviors compared with
      chronically epileptic Cre-/- littermates. Seizure susceptibility and associated
      depression-like behaviors can be restored to wild type levels by treating
      Gabrd/Crh mice with exogenous corticosterone. Similarly, chemogenetic activation
      of CRH neurons in the paraventricular nucleus (PVN) is sufficient to increase
      seizure susceptibility; whereas, chemogenetic inhibition of CRH neurons in the
      PVN of the hypothalamus is sufficient to decrease seizure susceptibility and
      depression-like behaviors in chronically epileptic mice. These data suggest that
      seizure-induced activation of the HPA axis promotes seizure susceptibility and
      comorbid depression-like behaviors, suggesting that the HPA axis may be a novel
      target for seizure control.

PMID- 29186695
TI  - Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of
      Alzheimer's Disease-like Pathology.
AB  - Amyloid beta (Abeta) peptides impair multiple cellular pathways and play a
      causative role in Alzheimer's disease (AD) pathology, but how the brain proteome
      is remodeled by this process is unknown. To identify protein networks associated
      with AD-like pathology, we performed global quantitative proteomic analysis in
      three mouse models at young and old ages. Our analysis revealed a robust increase
      in Apolipoprotein E (ApoE) levels in nearly all brain regions with increased
      Abeta levels. Taken together with prior findings on ApoE driving Abeta
      accumulation, this analysis points to a pathological dysregulation of the ApoE
      Abeta axis. We also found dysregulation of protein networks involved in
      excitatory synaptic transmission. Analysis of the AMPA receptor (AMPAR) complex
      revealed specific loss of TARPgamma-2, a key AMPAR-trafficking protein.
      Expression of TARPgamma-2 in hAPP transgenic mice restored AMPA currents. This
      proteomic database represents a resource for the identification of protein
      alterations responsible for AD.

PMID- 29186700
TI  - Quantifying the combined effects of land use and climate changes on stream flow
      and nutrient loads: A modelling approach in the Odense Fjord catchment (Denmark).
AB  - Water pollution and water scarcity are among the main environmental challenges
      faced by the European Union, and multiple stressors compromise the integrity of
      water resources and ecosystems. Particularly in lowland areas of northern Europe,
      high population density, flood protection and, especially, intensive agriculture,
      are important drivers of water quality degradation. In addition, future climate
      and land use changes may interact, with uncertain consequences for water
      resources. Modelling approaches have become essential to address water issues and
      to evaluate ecosystem management. In this work, three multi-stressor future
      storylines combining climatic and socio-economic changes, defined at European
      level, have been downscaled for the Odense Fjord catchment (Denmark), giving
      three scenarios: High-Tech agriculture (HT), Agriculture for Nature (AN) and
      Market-Driven agriculture (MD). The impacts of these scenarios on water discharge
      and inorganic and organic nutrient loads to the streams have been simulated using
      the Soil and Water Assessment Tool (SWAT). The results revealed that the scenario
      specific climate inputs were most important when simulating hydrology, increasing
      river discharge in the HT and MD scenarios (which followed the high emission 8.5
      representative concentration pathway, RCP), while remaining stable in the AN
      scenario (RCP 4.5). Moreover, discharge was the main driver of changes in organic
      nutrients and inorganic phosphorus loads that consequently increased in a high
      emission scenario. Nevertheless, both land use (via inputs of fertilizer) and
      climate changes affected the nitrate transport. Different levels of fertilization
      yielded a decrease in the nitrate load in AN and an increase in MD. In HT,
      however, nitrate losses remained stable because the fertilization decrease was
      counteracted by a flow increase. Thus, our results suggest that N loads will
      ultimately depend on future land use and management in an interaction with
      climate changes, and this knowledge is of utmost importance for the achievement
      of European environmental policy goals.

PMID- 29186701
TI  - Evaluation of the hydrological flow paths in a gravel bed filter modeling a
      horizontal subsurface flow wetland by using a multi-tracer experiment.
AB  - In recent years, constructed wetland systems have become into focus as means of
      cost-efficient organic contaminant management. Wetland systems provide a highly
      reactive environment in which several removal pathways of organic chemicals may
      be present at the same time; however, specific elimination processes and
      hydraulic conditions are usually separately investigated and thus not fully
      understood. The flow system in a three dimensional pilot-scale horizontal
      subsurface constructed wetland was investigated applying a multi-tracer test
      combined with a mathematical model to evaluate the flow and transport processes.
      The results indicate the existence of a multiple flow system with two distinct
      flow paths through the gravel bed and a preferential flow at the bottom
      transporting 68% of tracer mass resulting from the inflow design of the model
      wetland system. There the removal of main contaminant chlorobenzene was up to 52%
      based on different calculation approaches. Determined retention times in the
      range of 22d to 32.5d the wetland has a heterogeneous flow pattern. Differences
      between simulated and measured tracer concentrations in the upper sediment
      indicate diffusion dominated processes due to stagnant water zones. The tracer
      study combining experimental evaluation with mathematical modeling demonstrated
      the complexity of flow and transport processes in the constructed wetlands which
      need to be taken into account during interpretation of the determining
      attenuation processes.

PMID- 29186694
TI  - Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural
      Expression and Potential Nootropic Drug Targets.
AB  - Here, we present a large (n = 107,207) genome-wide association study (GWAS) of
      general cognitive ability ("g"), further enhanced by combining results with a
      large-scale GWAS of educational attainment. We identified 70 independent genomic
      loci associated with general cognitive ability. Results showed significant
      enrichment for genes causing Mendelian disorders with an intellectual disability
      phenotype. Competitive pathway analysis implicated the biological processes of
      neurogenesis and synaptic regulation, as well as the gene targets of two
      pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241,
      a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis
      revealed that the implicated loci were enriched for genes expressed across all
      brain regions (most strongly in the cerebellum). Enrichment was exclusive to
      genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we
      report genetic correlations between cognitive ability and disparate phenotypes
      including psychiatric disorders, several autoimmune disorders, longevity, and
      maternal age at first birth.

PMID- 29186703
TI  - Real world CO2 and NOx emissions from 149 Euro 5 and 6 diesel, gasoline and
      hybrid passenger cars.
AB  - In this study CO2 and NOx emissions from 149 Euro 5 and 6 diesel, gasoline and
      hybrid passenger cars were compared using a Portable Emissions Measurement System
      (PEMS). The models sampled accounted for 56% of all passenger cars sold in Europe
      in 2016. We found gasoline vehicles had CO2 emissions 13-66% higher than diesel.
      During urban driving, the average CO2 emission factor was 210.5 (sd. 47) gkm-1
      for gasoline and 170.2 (sd. 34) gkm-1 for diesel. Half the gasoline vehicles
      tested were Gasoline Direct Injection (GDI). Euro 6 GDI engines <1.4l delivered
      ~17% CO2 reduction compared to Port Fuel Injection (PFI). Gasoline vehicles
      delivered an 86-96% reduction in NOx emissions compared to diesel cars. The
      average urban NOx emission from Euro 6 diesel vehicles 0.44 (sd. 0.44) gkm-1 was
      11 times higher than for gasoline 0.04 (sd. 0.04) gkm-1. We also analysed two
      gasoline-electric hybrids which out-performed both gasoline and diesel for NOx
      and CO2. We conclude action is required to mitigate the public health risk
      created by excessive NOx emissions from modern diesel vehicles. Replacing diesel
      with gasoline would incur a substantial CO2 penalty, however greater uptake of
      hybrid vehicles would likely reduce both CO2 and NOx emissions. Discrimination of
      vehicles on the basis of Euro standard is arbitrary and incentives should promote
      vehicles with the lowest real-world emissions of both NOx and CO2.

PMID- 29186702
TI  - Bioaccumulation and risk assessment of organochlorine pesticides in fish from a
      global biodiversity hotspot: iSimangaliso Wetland Park, South Africa.
AB  - : Organochlorine pesticides (OCPs) have been used extensively in the eastern
      regions of South Africa for agricultural and malaria control purposes, yet few
      data exist on the local environmental and social impacts of these compounds. Such
      issues have become of increasing concern in the iSimangaliso World Heritage Site,
      where the continued use of OCPs may pose risks to several sensitive and protected
      species. This study was designed to examine the bioaccumulation of OCPs in two
      common fish species, Oreochromis mossambicus (Mozambique tilapia) and Clarias
      gariepinus (African sharptooth catfish) from iSimangaliso Wetland Park. These
      species are targeted by local subsistence fishermen and sustain substantial bird
      and crocodile populations. Our findings indicate widespread contamination of the
      aquatic environment, with SigmaOCP fish tissue concentrations in the range of
      6907-8740ngg-1 lw and 2953-5874ngg-1 lw for C. gariepinus and O. mossambicus,
      respectively. HCHs (471-1570ngg-1 lw), DDTs (645-2399ngg-1 lw), drin-related
      residues (589-1960ngg-1 lw), chlor-related residues (455-2162ngg-1 lw) and
      endosulfans (457-1495ngg-1 lw) were detected in all tissue samples.
      Concentrations detected in the majority of samples exceeded European Commission
      maximum residue limits and a health risk assessment indicated potential dietary
      risk associated with exposure to heptachlor, heptachlor epoxide and dieldrin.
      This study represents the first investigation into OCP bioaccumulation in fish
      species from iSimangaliso Wetland Park. Our findings highlight the need for more
      detailed investigations into the bioaccumulation and ecotoxicological effects of
      these contaminants in the food web and the associated risks to local ecosystems
      and human health. CAPSULE: High levels of OCPs detected in two common fish
      species at iSimangaliso Wetland Park highlight potential human health and
      ecotoxicological threats to a globally important biodiversity conservation
      hotspot.

PMID- 29186704
TI  - CRF35-AD as the Main Circulating Genotype of Human Immunodeficiency Virus Type 1
      Infection in Iran: A Phylogenetic and Demographic-Based Study.
AB  - Finding the predominant circulating subtype of human immunodeficiency virus type
      1 (HIV-1) and surveying co-infection with other infectious viruses are crucial to
      making preventive decisions. To this end, 50 Iranian HIV-positive patients made
      up of 37 men and 13 women were selected. Most of the HIV-positive patients (70%)
      were intravenous drug users (IDUs), and 48 and 32% of patients were co-infected
      with HCV and HBV, respectively. The rate of simultaneous infection with HIV, HCV,
      and HBV was found to be 6%. The p17 region of the gag and the c2-v5 region of the
      env genes were sequenced and then clustered by phylogenetic analyses. CRF35-AD
      was specified as the predominant circulating subtype among different high-risk
      groups. In our survey, most of the patients in the IDU group had co-infections
      with HCV and HBV. Some possible reasons for the increased transmission risk of
      HIV in IDUs could be low levels of education, poor hygiene and housing
      conditions, and limited access to health services.

PMID- 29186705
TI  - Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix
      Metalloproteinases and Tissue Inhibitors of Metalloproteinases.
AB  - BACKGROUND/AIMS: Stem cell treatment is one of the potential treatment options
      for ischemic stroke. We recently demonstrated a protective effect of human
      umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in a rat model of
      ischemic stroke. The treatment attenuated apoptosis and prevented DNA damage. A
      collection of published studies, including several from our laboratory, indicated
      the induction and detrimental role for several matrix metalloproteinases (MMPs)
      in post-stroke brain injury. We hypothesized that the HUCB-MSCs treatment after
      focal cerebral ischemia prevents the dysregulation of MMPs and induces the
      expression of endogenous tissue inhibitors of metalloproteinases (TIMPs) to
      neutralize the elevated activity of MMPs. METHODS: To test our hypothesis, we
      administered HUCB-MSCs (0.25 million cells/animal and 1 million cells/animal)
      intravenously via tail vein to male Sprague-Dawley rats that were subjected to a
      transient (two-hour) right middle cerebral artery occlusion (MCAO) and one-day
      reperfusion. Ischemic brain tissues obtained from various groups of rats seven
      days after reperfusion were subjected to real-time PCR, immunoblot, and
      immunofluorescence analysis. RESULTS: HUCB-MSCs treatment prevented the induction
      of MMPs, which were upregulated in ischemia-induced rats that received no
      treatment. HUCB-MSCs treatment also prevented the induction of TIMPs expression.
      The extent of prevention of MMPs and TIMPs induction by HUCB-MSCs treatment is
      similar at both the doses tested. CONCLUSION: Prevention of stroke-induced MMPs
      upregulation after HUCB-MSCs treatment is not mediated through TIMPs
      upregulation.

PMID- 29186706
TI  - Type 2 Diabetes and Heart Failure - More Scrutiny Wanted!

PMID- 29186707
TI  - Early Use of Mother's Own Raw Milk, Maternal Satisfaction, and Breastfeeding
      Continuation in Hospitalised Neonates: A Prospective Cohort Study.
AB  - BACKGROUND: Despite the critical importance of breast milk for preterm and sick
      neonates, there is no consensus regarding the use of raw mother's own milk (MOM)
      in neonatal units. OBJECTIVES: This study aimed to describe the use of raw MOM in
      hospitalised neonates before day 7 (early use), and to investigate: (i) related
      factors, (ii) maternal satisfaction, and (iii) the association with breastfeeding
      continuation. METHODS: This prospective cohort included 516 neonates intended to
      be breastfed in 2 French neonatal units. Neonates receiving raw MOM before day 7
      were compared to those who did not. The association between early use of MOM and
      breastfeeding continuation at hospital discharge, and up to 6 months later, was
      measured by logistic regression. RESULTS: More than one-third (36.2%) of
      breastfed neonates did not receive any MOM during their first week, mainly due to
      organisational constraints and staff reluctance. Maternal satisfaction related to
      early raw MOM use was high (96%), and was coupled with a more frequent maternal
      feeling of being supported in breastfeeding (p = 0.003). There was a significant
      association between early use of MOM and breastfeeding continuation at discharge
      (OR 2.92, 95% CI 1.94-4.40, p < 0.0001), which persisted 6 months later (OR 2.70,
      95% CI 1.21-6.03, p = 0.023). This association appeared independent in
      multivariable analyses (at discharge: aOR 2.03, 95% CI 1.27-3.25, p = 0.003; 6
      months later: aOR 2.46, 95% CI 1.02-5.92, p = 0.045). CONCLUSION: While the early
      use of raw MOM in hospitalised neonates can be limited by multiple factors, it
      appears supportive for mothers, and might represent a simple opportunity to
      improve breastfeeding in neonatal units.

PMID- 29186709
TI  - Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and
      Mouse Islets Reveals Differential Glucose Sensitivity.
AB  - BACKGROUND/AIMS: Rodent islets are often used for basic science research but they
      do not always recapitulate signalling events in human islets. This study
      evaluated the glucose-dependent responses of human and mouse islets in terms of
      dynamic insulin secretion, metabolic coupling and the role of glucose
      transporters. METHODS: Glucose-induced insulin secretion from isolated mouse and
      human islets was profiled by perifusion and islet ATP levels were measured by
      chemoluminescence assay. Glucose transporter expression was determined by qPCR
      and western blotting. RESULTS: Human islets show a left-shifted glucose
      concentration-insulin secretion profile compared to mouse islets. These data are
      consistent with glucose transporter expression, with human islets expressing
      mainly GLUT1 and GLUT3, and GLUT2 being the predominant transporter in mouse
      islets. Using the GLUT1 inhibitor STF-31 we unveiled an important role for GLUT1
      for differences in glucose-induced insulin secretion profiles observed between
      the two species. CONCLUSION: The high affinity of GLUT1/3 for glucose reflects
      the left-shifted glucose-induced insulin secretory response of human islets and
      the impairment of insulin secretion from human islets after STF-31 treatment
      indicates an important role for GLUT1 in human islet stimulus-secretion coupling.
      Our data provide further insight into key differences between insulin secretion
      regulation in mouse and human islets.

PMID- 29186708
TI  - Isogambogenic Acid Inhibits the Growth of Glioma Through Activation of the AMPK
      mTOR Pathway.
AB  - BACKGROUND/AIMS: Glioma is the most devastating cancer in the brain and has a
      poor prognosis in adults. Therefore, there is a critical need for novel
      therapeutic strategies for the management of glioma patients. Isogambogenic acid,
      an active compound extracted from the Chinese herb Garcinia hanburyi, induces
      autophagic cell death. METHODS: Cell viability was detected with MTT assays. Cell
      proliferation was assessed using the colony formation assay. Morphological
      changes associated with autophagy and apoptosis were tested by TEM and Hoechst
      staining, respectively. The apoptosis rate was measured by flow cytometry.
      Western blot, immunofluorescence and immunohistochemical analyses were used to
      detect protein expression. U87-derived xenografts were established for the
      examination of the effect of isogambogenic acid on glioma growth in vivo.
      RESULTS: Isogambogenic acid induced autophagic death in U87 and U251 cells, and
      blocking late-stage autophagy markedly enhanced the antiproliferative activities
      of isogambogenic acid. Moreover, we observed the activation of AMPK-mTOR
      signalling in isogambogenic acid-treated glioma cells. Furthermore, the
      activation of AMPK or the inhibition of mTOR augmented isogambogenic acid-induced
      autophagy. Inhibition of autophagy attenuated apoptosis in isogambogenic acid
      treated glioma cells. Finally, isogambogenic acid inhibited the growth of U87
      glioma in vivo. CONCLUSION: Isogambogenic acid inhibits the growth of glioma via
      activation of the AMPK-mTOR signalling pathway, which may provide evidence for
      future clinical applications in glioma therapy.

PMID- 29186710
TI  - ADAMTS9 is Silenced by Epigenetic Disruption in Colorectal Cancer and Inhibits
      Cell Growth and Metastasis by Regulating Akt/p53 Signaling.
AB  - BACKGROUND/AIMS: ADAMTS (disintegrin-like and metalloproteinase with
      thrombospondin motifs) proteins are extracellular zinc metalloproteinases that
      play an important role in extracellular matrix assembly and degradation,
      connective tissue structuring, angiogenesis, and cell migration. Multiple studies
      suggest that ADAMTS proteins (e.g. ADAMTS9) can act as tumor suppressors. In
      gastric, esophageal, and nasopharyngeal carcinomas ADAMTS9 is frequently down
      regulated by promoter methylation. Whether ADAMTS9 can function as a tumor
      suppressor gene (TSG) in colorectal cancer is still unclear. METHODS: We
      performed immunohistochemistry, RT-PCR, and qRT-PCR, to examine the expression of
      ADAMTS9 in colorectal cancer cell lines and primary colorectal cancer tissues.
      Methylation-specific PCR was also carried out to investigate the promoter
      methylation status of ADAMTS9. We also explored the functions of ADAMTS9 in
      colorectal cancer cell lines through in vitro experiments. RESULTS: ADAMTS9
      expression was down-requlated or silenced in 83.3% (5/6) of colorectal cancer
      cell lines, and frequently repressed in 65.6% (21/32) of colorectal cancer
      tissues. Down-regulation of ADAMTS9 was partially due to promoter methylation.
      Exogenous expression of ADAMTS9 in colorectal cancer cell lines inhibited cell
      proliferation and migration through the regulation of cell cycle and apoptosis.
      In addition, ADAMTS9 prevented the activation of Akt, and its downstream targets
      in colorectal cancer cell lines. CONCLUSION: Our findings suggest ADAMTS9 is a
      TSG in colorectal cancer.

PMID- 29186711
TI  - Genomic Organization of Repetitive DNAs and Differentiation of an XX/XY Sex
      Chromosome System in the Amazonian Puffer Fish, Colomesus asellus
      (Tetraodontiformes).
AB  - The genus Colomesus is the sole representative of the family Tetraodontidae in
      the Amazon region. Here, Colomesus asellus was analyzed using conventional and
      molecular cytogenetic protocols. Its diploid chromosome number is 2n = 46 with 12
      meta-, 10 submeta-, 16 subtelo-, and 8 acrocentric chromosomes and a fundamental
      number of FN = 84. An XX/XY sex chromosome system was identified. Mapping of 18S
      rDNA correlated with the nucleolus organizer regions (Ag-NORs) in the short arms
      of the 2 X chromosomes in females and in the Y chromosome in males. C-banding
      revealed heterochromatin in the centromeric regions of all chromosomes, except
      for pair 3. Prominent sex chromosome-specific heterochromatin amplification was
      observed, covering the short arms of the Y chromosome almost entirely. FISH with
      telomeric and tropomyosin (tpm1) sequences, respectively, revealed terminal
      signals in all chromosomes. The analysis of extended DNA fibers confirmed the
      colocalization and the interspersed pattern of the telomeric and tpm1 sequences.
      Thus, this study highlights the remarkable evolutionary dynamism presented by the
      Amazonian puffer fish regarding the differentiation of a heteromorphic XY sex
      chromosome system and a particular sex-specific amplification of rDNA sites. This
      is the first record of such an association in the Tetraodontidae family.

PMID- 29186713
TI  - Phosphatidylcholine Causes Lipolysis and Apoptosis in Adipocytes through the
      Tumor Necrosis Factor Alpha-Dependent Pathway.
AB  - A phosphatidylcholine (PPC) formulation has been used to treat cellulite;
      however, its underlying mechanism of action remains unclear. In this study, we
      demonstrated that PPC induces lipolysis and apoptosis in adipocytes, and
      evaluated a possible tumor necrosis factor alpha (TNFalpha)-dependent pathway,
      whereby PPC exerts these effects. For in vitro study, fully differentiated 3T3-L1
      cells, mouse adipocytes were treated with various concentrations of PPC and cell
      apoptosis and lipolysis were assayed. For in vivo experiments, mice fed on a high
      fat diet for 8 weeks were injected twice to abdominal subcutaneous fat tissues of
      either vehicle or PPC. We found that PPC induced lipolysis and apoptosis dose
      dependently in fully differentiated 3T3-L1 cells. In addition, PPC augmented both
      expression and release of TNFalpha in a dose-dependent fashion. Induction of
      TNFalpha by PPC was associated with the stimulation of nuclear factor kappa B
      (NFkappaB)-mediated transcriptional activity. Small interfering RNA (siRNA)
      mediated suppression of NFkappaB abrogated the effect of PPC on TNFalpha
      secretion. Suppression of TNFalpha with specific siRNA abrogated the effects of
      PPC on lipolysis and apoptosis. Through in vivo experiments, we demonstrated that
      PPC injection not only stimulated the local lipolysis and apoptosis, resulting in
      weight loss, but also induced TNFalpha mRNA expression and neutrophil
      infiltration. Furthermore, PPC injection prevented lipogenesis and suppressed the
      mRNA -expression of adipokines (such as adiponectin and leptin), due to the down
      sizing of adipocytes. In conclusion, we suggest that PPC induces lipolysis and
      apoptosis in adipocytes through TNFalpha-dependent pathways.

PMID- 29186712
TI  - Reproductive Hormones and Their Receptors May Affect Lung Cancer.
AB  - BACKGROUND/AIMS: In contrast to men, women have experienced a rapid increase in
      lung cancer mortality. Numerous studies have found that the sex differences in
      lung cancer are due to reproductive hormones. Experiments in female mice with and
      without ovariectomy were performed to explore the possible mechanism by which sex
      hormones (and their receptors) influence lung cancer. METHODS: Twenty-four female
      C57BL/6 mice aged 56-62 days were randomly divided into the ovariectomized group
      and the control group. In the ovariectomized group, the bilateral ovaries were
      removed via the dorsal approach, while the control group underwent a sham
      operation with bilateral ovarian fat resection at the same sites. After 3 weeks
      of recovery, Lewis lung cancer cells were transplanted into these mice by
      subcutaneous inoculation of a tumour cell suspension to establish the
      ovariectomized lung cancer model. Beginning on the 6th day after subcutaneous
      inoculation, mouse weight and transplanted tumour volume were measured every 3
      days. After 3 weeks, all the mice were killed by cervical dislocation, and we
      measured the tumour weight. Mouse serum and tumour tissues were removed. Then,
      the serum levels of E2 (oestradiol) and T (testosterone) were detected by ELISA;
      the protein expression levels of AR (androgen receptor), ERalpha (oestrogen
      receptor alpha) and ERbeta (oestrogen receptor beta) were detected by Western
      Blot and IHC (immunohistochemistry); and the mRNA expression levels of AR,
      ERalpha and ERbeta were detected by qRT-PCR (quantitative real-time polymerase
      chain reaction) in the ovariectomized and control groups. RESULTS: Compared with
      the control group, both mouse weight and transplanted tumour volume increased
      rapidly in the ovariectomized group, and the transplanted tumour weight was
      significantly heavier in the ovariectomized group (1.83+/-0.40 and 3.13+/-0.43,
      P<0.05). E2 and T serum levels decreased exponentially in the ovariectomized
      group, while the E2/T ratio increased compared with the control group (E2:
      55.88+/-11.45 and 78.21+/-9.37; T: 0.82+/-0.14 and 1.46+/-0.16; ratio: 69.62+/
      14.43+/-29.81 and 52.22+/-5.42; all P<0.05). The Western blot and IHC results
      indicated that AR, ERalpha and ERbeta protein expression levels were obviously
      higher in transplanted tumour and lung tissues from the ovariectomized group,
      with particular increases in ERbeta in transplanted tumour tissue and in ERalpha
      in lung tissue. The PCR results also showed markedly higher mRNA expression
      levels of AR, ERalpha and ERbeta in the ovariectomized group, and in particular,
      ERbeta in transplanted tumour tissue and ERalpha in lung tissue were
      significantly increased in the ovariectomized group. CONCLUSION: Ovariectomy
      decreased E2 and T serum levels and increased the E2/T ratio in mice, and this
      imbalance in the internal environment promoted the growth of transplanted
      tumours. Sex hormone disorder not only promoted transplanted tumour growth but
      also significantly reduced the protein and mRNA expression levels of sex hormone
      receptors. The metabolism of E2 and T may affect the growth, proliferation and
      metabolism of lung cancer cells, and the mechanism by which sex hormones and
      their receptors influence lung cancer is worthy of further research.

PMID- 29186714
TI  - Enhanced Immunological Tolerance by HLA-G1 from Neural Progenitor Cells (NPCs)
      Derived from Human Embryonic Stem Cells (hESCs).
AB  - BACKGROUND: Despite the great potential of utilizing human embryonic stem cells
      (hESCs)-derived cells as cell source for transplantation, these cells were often
      rejected during engraftment by the immune system due to adaptive immune response.
      METHODS: We first evaluated HLA-G expression level in both hESCs and
      differentiated progenitor cells. After that, we generated modified hESC lines
      that over-express HLA-G1 using lentiviral infection with the construct contains
      both HLA-G1 and GFP tag. The lentivirus was first produced by co-transfecting HLA
      G1 expressing lentiviral vector together with packaging vectors into packaging
      cell line 293T. Then the produced virus was used for the infection of selected
      hESC lines. We characterized the generated cell lines phenotype, including
      pluripotency and self-renewal abilities, as well as immune tolerance ability by
      mixed lymphocyte reaction (MLR) and cytotoxicity assays. RESULTS: Although the
      hESCs do not express high levels of HLA-G1, over-expression of HLA-G1 in hESCs
      still retains their stem cell characteristics as determined by retaining the
      expression levels of OCT4 and SOX2, two critical transcriptional factors for stem
      cell function. Furthermore, the HLA-G1 overexpressing hESCs retain the self
      renewal and pluripotency characteristics of stem cells, which can differentiate
      into different types of cells, including pigment cells, smooth muscle cells,
      epithelia-like cells, and NPCs. After differentiation, the differentiated cells
      including NPCs retain the high levels of HLA-G1 protein. In comparison with
      conventional NPCs, these HLA-G1 positive NPCs have enhanced immune tolerance
      ability. CONCLUSIONS: Ectopic expression of HLA-G1, a non-classical major
      histocompatibility complex class I (MHC I) antigen that was originally discovered
      involving in engraftment tolerance during pregnancy, can enhance the
      immunological tolerance in differentiated neural progenitor cells (NPCs). Our
      study shows that stably overexpressing HLA-G1 in hESCs might be a feasible
      strategy for enhancing the engraftment of NPCs during transplantation.

PMID- 29186715
TI  - Thulium Vaporesection of the Prostate and Thulium Vapoenucleation of the
      Prostate: A Retrospective Bicentric Matched-Paired Comparison with 24-Month
      Follow-Up.
AB  - INTRODUCTION: To evaluate the intermediate-term outcomes of thulium
      vapoenucleation of the prostate (ThuVEP) and thulium vaporesection of the
      prostate (ThuVaRP) in patients with benign prostate obstruction (BPO). MATERIALS
      AND METHODS: A bicentric retrospective matched-paired comparison of patients
      treated by ThuVEP (n = 80) or ThuVaRP (n = 80) was performed. The patients were
      preoperatively assessed with International Prostate Symptom Score (IPSS), quality
      of life (QoL), post-void residual urine (PVR), maximum urinary flow rate (Qmax),
      prostatespecific antigen (PSA) and re-evaluated at 12- and 24-month follow-up.
      RESULTS: Median prostate volume was 65 mL and not different between the groups.
      The immediate re-operation rate was significantly different between ThuVEP and
      ThuVaRP (5 vs. 0%, p <= 0.0434). IPSS, QoL, Qmax and PVR had improved
      significantly compared to preoperative assessment in both groups at 12- and 24
      month follow-up (p <= 0.001). Median Qmax (18.2 vs. 21.0 mL/s) and PVR (29.4 vs.
      0 mL) were significantly different between ThuVEP and ThuVaRP at 24-month follow
      up (p <= 0.001), while IPSS and QoL showed no differences between the groups.
      However, the PSA reduction was significantly higher after ThuVEP compared to
      ThuVaRP (78.93 vs. 23.39%, p <= 0.006) at 24-month follow-up. CONCLUSIONS: ThuVEP
      and ThuVaRP are safe and efficacious procedures for patients with BPO. Although
      the peri-operative re-intervention rates were lower after ThuVaRP, the low PSA
      reduction rate after ThuVaRP at 24-month follow-up favours the ThuVEP procedure.

PMID- 29186717
TI  - Joint 7th Annual Scientific Session of the Stroke Prevention and Control Society
      and Chinese Preventive Medicine Association (SPCS, CPMA) and 6th International
      Conference on Neurology and Epidemiology (ICNE). Xiamen, China, December 1-3,
      2017: A Selection of Abstracts.

PMID- 29186716
TI  - Muller Cell-Derived PEDF Mediates Neuroprotection via STAT3 Activation.
AB  - : Background/ Aims: This study was performed to reveal signaling pathways
      exploited by pigment epithelium-derived factor (PEDF) derived from retinal
      (glial) Muller cells to protect retinal ganglion cells (RGCs) from cell death.
      METHODS: The survival of RGCs was determined in the presence of conditioned
      culture media (MCM) from or in co-cultures with Muller cells. The significance of
      PEDF-induced STAT3 activation was evaluated in viability assays and using Western
      blotting analyses and siRNA-transfected cells. RESULTS: Secreted mediators of
      Muller cells increased survival of RGCs under normoxia or hypoxia to a similar
      degree as of PEDF- or IL-6-exposed cells. PEDF and MCM induced an increased STAT3
      activation in RGCs and R28 cells, and neutralization of PEDF in MCM attenuated
      STAT3 activation. Inhibition of STAT3 reduced PEDF-promoted survival of RGCs.
      Similar to IL-6, PEDF induced STAT3 activation, acting in a dose-dependent manner
      via the PEDF receptor (PEDF-R) encoded by the PNPLA2 gene. Ablation of PEDF-R
      attenuated MCM-induced STAT3 activation and compromised the viability of PEDF
      exposed R28 cells. CONCLUSIONS: Muller cells are an important source of PEDF,
      which promotes RGC survival through STAT3 activation and, at least in part, via
      PEDF-R. Enhancing the secretory function of Muller cells may be useful to promote
      RGC survival in retinal neurodegenerative diseases.

PMID- 29186718
TI  - Interferon-Stimulated Genes as Enhancers of Antiviral Innate Immune Signaling.
AB  - The ability of a host to curb a viral infection is heavily reliant on the
      effectiveness of an initial antiviral innate immune response, resulting in the
      upregulation of interferon (IFN) and, subsequently, IFN-stimulated genes (ISGs).
      ISGs serve to mount an antiviral state within a host cell, and although the
      specific antiviral function of a number of ISGs has been characterized, the
      function of many of these ISGs remains to be determined. Recent research has
      uncovered a novel role for a handful of ISGs, some of them directly induced by
      IFN regulatory factor 3 in the absence of IFN itself. These ISGs, most with
      potent antiviral activity, are also able to augment varying arms of the innate
      immune response to viral infection, thereby strengthening this response. This new
      understanding of the role of ISGs may, in turn, help the recent advancement of
      novel therapeutics aiming to augment innate signaling pathways in an attempt to
      control viral infection and pathogenesis.

PMID- 29186719
TI  - Single-Incision Laparoscopic Splenectomy for an Unruptured Aneurysm of the
      Splenic Artery.
AB  - OBJECTIVE: We describe our experience of single-incision laparoscopic splenectomy
      (SILS) for an unruptured aneurysm of the splenic artery. CLINICAL PRESENTATION
      AND INTERVENTION: A 73-year-old woman was diagnosed as having a splenic aneurysm
      which grew from 14 to 22 mm in diameter within 2 years. Due to a contrast agent
      allergy, transcatheter arterial embolization could not be performed; therefore,
      SILS was performed with a 4-cm Z-shaped incision. The operative time and
      intraoperative blood loss were 132 min and 27 mL, respectively. The patient was
      discharged 4 days after surgery. CONCLUSION: In selected cases, SILS is a
      suitable and safe procedure for an unruptured aneurysm of the splenic artery.

PMID- 29186720
TI  - Archaeal and Bacterial Community Structure in an Anaerobic Digestion Reactor
      (Lagoon Type) Used for Biogas Production at a Pig Farm.
AB  - Biogas production from animal waste is an economically viable way to reduce
      environmental pollution and produce valuable products, i.e., methane and a
      nutrient-rich organic waste product. An anaerobic digestion reactor for biogas
      production from pig waste was sampled at the entrance, middle (digestion
      chamber), and exit of a digester, while the bacterial and archaeal community
      structure was studied by 16S rRNA gene metagenomics. The number of bacterial
      operational taxonomic units (OTU)-97% was 3-7 times larger than that of archaeal
      ones. Bacteria and Archaea found in feces of animals (e.g., Clostridiaceae,
      Lachnospiraceae, Ruminococcaceae, Methanosarcina, Methanolobus, Methanosaeta, and
      Methanospirillum) dominated the entrance of the digester. The digestion chamber
      was dominated by anaerobic sugar-fermenting OP9 bacteria and the syntrophic
      bacteria Candidatus Cloacamonas (Waste Water of Evry 1; WWE1). The methanogens
      dominant in the digestion chamber were the acetoclastic Methanosaeta and the
      hydrogenothrophic Methanoculleus and Methanospirillum. Similar bacterial and
      archaeal groups that dominated in the middle of the digestion chamber were found
      in the waste that left the digester. Predicted functions associated with
      degradation of xenobiotic compounds were significantly different between the
      sampling locations. The microbial community found in an anaerobic digestion
      reactor loaded with pig manure contained microorganisms with biochemical
      capacities related to the 4 phases of methane production.

PMID- 29186722
TI  - IL-33 Expression in Chronic Rhinosinusitis with Nasal Polyps and Its Relationship
      with Clinical Severity.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized
      by epithelial inflammation and tissue eosinophilic infiltration. Interleukin-33
      (IL-33) is a key inflammatory cytokine that mediates eosinophilic infiltration.
      OBJECTIVE: The aim of our study was to investigate the expression and role of IL
      33 in eosinophilic CRS with nasal polyps (ECRSwNP) and in noneosinophilic CRS
      with nasal polyps (nECRSwNP), and to analyze their correlation with clinical
      severity. METHODS: The study enrolled 25 patients with ECRSwNP, 27 patients with
      nECRSwNP, and 12 control subjects, based on immunohistochemical staining. Protein
      and mRNA expressions of IL-33 in sinus mucosal samples were determined by
      immunohistochemistry and real-time polymerase chain reaction. Sino-Nasal Outcome
      Test-20 (SNOT-20) score, visual analog scale (VAS) score, endoscopy score, and
      computed tomography (CT) score were assessed preoperatively. RESULTS: IL-33
      expression levels in the CRSwNP group were significantly higher than those in the
      control group (p < 0.01), especially in the ECRSwNP group (p < 0.05). There were
      no significant differences between the ECRSwNP and nECRSwNP groups with respect
      to SNOT-20 score, VAS score, endoscopy score, or CT score. IL-33 mRNA expression
      showed a positive correlation with the number of eosinophils (p < 0.05) and
      endoscopy score (p < 0.05) but not with VAS score and CT score. CONCLUSION: IL-33
      expression plays an important role in patients with CRSwNP. No significant
      differences were observed between the ECRSwNP and nECRSwNP groups with respect to
      SNOT-20 score, VAS score, endoscopy score, or CT score. IL-33 expression was
      correlated with eosinophil counts and endoscopy score.

PMID- 29186723
TI  - Optical Coherence Tomography Angiography in Optic Nerve Drusen.
AB  - AIM: To determine the efficacy of optical coherence tomography angiography (OCT
      A) in diagnosing optic nerve head flow impairment in patients with optic nerve
      drusen. METHODS: Patients affected by optic-nerve head drusen (ONHD) attending
      the Eye Clinic of the Federico II University of Naples were enrolled in this
      prospective case series between October 2015 and October 2016. Each patient
      underwent evaluation of best corrected visual acuity (BCVA), Goldman applanation
      tonometry, slit-lamp biomicroscopy, fundus examination, standard visual-field
      testing (perimetry), spectral domain (SD)-OCT and OCT-A. RESULTS: Thirteen
      patients (6 females and 7 males with a mean age of 22.05 +/- 7.54 years) with
      ONHD (19 eyes) were enrolled. Mean BCVA was 0.16 +/- 0.21 LogMar and mean
      intraocular pressure was 15.68 +/- 1.66 mm Hg. The control group constituted 16
      individuals (24 eyes). Both ganglion cell complex (GCC) and retinal nerve fiber
      layer (RNFL) parameters were lower in patients than in controls. Similarly, the
      flow index (U = 134, p = 0.021) and vessel density (U = 90, p = 0.001) were
      significantly lower in eyes affected by ONHD than in normal eyes. Visual-field
      parameters did not differ between the 2 groups. GCC parameters were significantly
      correlated with OCT-A parameters (p < 0.05). No correlation was found between
      RNFL and OCT-A parameters. CONCLUSIONS: Our data suggest that OCT-A could be an
      objective method, helpful in the analysis of flow changes in patients with ONHD.

PMID- 29186721
TI  - n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: Principles,
      Practices, Pitfalls, and Promises - A Contemporary Review.
AB  - Amidst voluminous literature, inconsistencies and opposing results have confused
      rather than clarified cardiologists' ability to assess the potential benefits of
      n-3 polyunsaturated fatty acids (n-3 PUFA). In perspective, there are common
      themes that emerge from n-3 PUFA studies, even as imperfect as they may be. The
      approach taken was to identify and unite these themes into a manageable,
      cohesive, evidence-based, yet useful synthesis. In all reviews and meta-analyses,
      the selection of component studies and assumptions influences outcomes. This
      overarching principle must be combined with the totality of the data,
      particularly when evidence is incompletely understood and gaps in knowledge must
      be bridged. Both the older literature and the most recent rigorous meta-analyses
      indicate that n-3 PUFA are highly pleiotropic agents with many documented
      positive physiological effects. Concordance among preclinical, observational,
      randomized clinical trials and meta-analyses is impressive. These agents have
      modest, statistically significant benefits which accrue over time. Given their
      favorable safety profile, a risk reduction of about 10% justifies their potential
      use in cardiovascular disease.

PMID- 29186724
TI  - [Establishing Prevention Reporting in Bavaria - Concept, Implementation and First
      Results].
AB  - BACKGROUND: Bavaria is currently embarking on the endeavour of building up
      systematic prevention reporting. Prevention reporting is meant to support the
      implementation of the Bavarian Prevention Plan and the German Prevention Law and
      to further the ongoing development in the field of health promotion and health
      related prevention in Bavaria. GOALS: Prevention reporting in Bavaria aims to
      draw on general health reporting and complement it with specific prevention
      related data taking into special consideration the Bavarian Prevention Plan.
      Particularly, data on prevention-amenable health determinants, prevention
      interventions, prevention spending and on indicators related to the targets of
      the Bavarian Prevention Plan are meant to be included. Periodic reporting will
      allow ongoing monitoring and the observation of trends. The reporting system will
      encompass shorter publications for the general public as well as more extensive
      reports for an expert audience. Where possible, data will be reported not only
      Bavaria wide but also on a smaller regional level to support local action.
      IMPLEMENTATION AND FIRST RESULTS: An extensive stocktaking of prevention and
      health promotion activities in Bavaria in 2014/2015 as well as a survey of the
      partner organisations in the Bavarian Prevention Alliance in 2016 presented an
      overview of the prevention scene in Bavaria. A core indicator set to support the
      implementation of the Bavarian Prevention Plan was developed in 2016 and a first
      short data brochure for the public was published. A comprehensive compilation of
      prevention-related data and a Bavarian prevention report are planned for 2017 and
      2018. CONCLUSIONS: Like health reporting, prevention reporting, as conceptualised
      in Bavaria, presents overview data and thus allows a monitoring of prevention.
      For specific planning or evaluation purposes, it needs to be supplemented by more
      in-depth analyses. Current challenges include the development of valid,
      prevention-specific indicators, the generation of an empiric database and the
      attempt of a coordinated approach amongst the federal states within Germany.

PMID- 29186725
TI  - [Screening of executive functions in patients with Parkinson's disease using the
      new rapid test PAL-5].
AB  - Parkinson's disease (PD) is the second most prevalent chronic neurodegenerative
      disorder worldwide, following Alzheimer's disease. Along with the characteristic
      motor symptoms of the disorder, especially bradykinesia, cognitive deficits can
      often be found prior to the onset of the disorder. These mainly concern executive
      functioning. To detect cognitive deficits at an early stage, initial screening
      procedures are recommended. The new cognitive rapid test Paarassoziationslernen-5
      ("PAL-5") has been developed to detect the most prevalent cognitive symptoms -
      namely executive impairments - of PD patients. It consists of a direct recall of
      five incompatible and newly jointed word pairs (capitals vs. countries), an
      intermediate formal lexical word fluency task ("FAS-Test") and a delayed recall.
      Thereby, the three major executive functioning processes are tested: cognitive
      flexibility, inhibition and memory. In the department of neurology of the
      University Clinic of Cologne, the PAL-5 was completed by 154 PD patients, 115
      participants with cognitive deficits without a PD diagnosis and 115 controls (N =
      384) between 2014 and 2016. For purposes of retest reliability determination,
      another 42 controls were examined from February to July 2017, with a four-month
      time interval between the initial and second test. Highly significant group
      differences have been found. PD patients and cognitive impaired participants
      scored significantly lower than the control group. A comparison of PD patients
      and cognitively impaired participants did not reveal significant group
      differences. Additionally, a moderate to high correlation between PAL-5 and MMST
      as well as PAL-5 and PANDA was found (respectively p < .001). An ROC analysis of
      the PAL-5 total score of PD patients with a score lower than 11 showed an AUC of
      .91. Therefore, a cut-off of <= 10 seems to be practicable to detect cognitive
      deficits - especially executive functioning deficits and memory impairments - in
      PD patients. It has been shown that cognitive flexibility, inhibition and memory
      is a short useful combination for a screening procedure of PD patients.

PMID- 29186726
TI  - [Death anxiety and its importance for psychiatry].
AB  - Inner dealing with the question of death as well as death anxiety accompany human
      beings from the beginning, which is reflected by the different philosophical and
      religious positions. It is obvious that work on this issue is sparse in the field
      of psychiatric disorders. Due to the few literatures it can however be assumed
      that death anxiety plays a greater role within the changed thoughts and feelings
      of psychiatric patients, whose intensity we probably determine and assess in non
      sufficient manner yet. The terms are defined and the problematic of ego
      destruction in patients with schizophrenia as expression of death anxiety is
      specifically discussed. Furthermore, the few studies about death anxiety in
      psychiatric disorders, its psychodynamics and approaches of the so-called terror
      management theory are presented besides other aspects. The current state of
      literature is presented, points out the importance of this issue for our field
      and wants to initiate more research on this topic.

PMID- 29186727
TI  - Cardiac Air Embolism in Neonates: A Hemodynamic Perspective.
AB  - Cardiac air embolism should be suspected in any neonate with acute unexplained
      cardiovascular collapse or worsening oxygenation. We present here five cases that
      presented with the above symptoms. A comprehensive evaluation including targeted
      neonatal echocardiography and near-infrared spectroscopy helped confirm the
      diagnosis and assess the hemodynamic state. Management was supportive including
      left lateral positioning, chest compressions, and cardiovascular medications to
      treat pulmonary hypertension and systemic hypotension.

PMID- 29186728
TI  - Video Comment on Kavel Visrodia et al.

PMID- 29186729
TI  - Video Comment on Oscar V. Hernandez Mondragon et al.

PMID- 29186730
TI  - Video Comment on Taimur Khan et al.

PMID- 29186731
TI  - Reprocessing single-use devices: A new season in a long-running show? A European
      perspective.

PMID- 29186732
TI  - The 10-year repeat after a negative colonoscopy.

PMID- 29186733
TI  - Endoscopic submucosal dissection for inflammatory bowel disease-related
      dysplasia: feasible, but be ready for a difficult procedure.

PMID- 29186734
TI  - Should we focus on the fight against achalasia or equivocal results of reflux
      after peroral endoscopic myotomy?

PMID- 29186735
TI  - Gastroesophageal reflux after peroral endoscopic myotomy.

PMID- 29186736
TI  - Reply to Eleftheriadis and to Sharma et al.

PMID- 29186737
TI  - The role of confocal laser endomicroscopy in assessing mucosal healing in
      patients with ulcerative proctitis.

PMID- 29186738
TI  - Reply to Gheorghe et al.

PMID- 29186739
TI  - [French comment on article Reprocessing of single-use endoscopic variceal band
      ligation devices: a pilot study].

PMID- 29186740
TI  - [French comment on article Long-term quality of life after peroral endoscopic
      myotomy remains compromised in patients with achalasia type III].

PMID- 29186741
TI  - [French comment on article Systematic assessment with I-SCAN magnification
      endoscopy and acetic acid improves dysplasia detection in patients with Barrett's
      esophagus].

PMID- 29186742
TI  - [French comment on article Didactic training vs. computer-based self-learning in
      the prediction of diminutive colon polyp histology by trainees: a randomized
      controlled study].

PMID- 29186743
TI  - [French comment on article Risk of colorectal cancer after a negative colonoscopy
      in low-to-moderate risk individuals: impact of a 10-year colonoscopy].

PMID- 29186744
TI  - Pediatric Spinal Deformities.

PMID- 29186745
TI  - [Laserhemorrhoidoplasty with 1470 nm Diode Laser in the Treatment of Second to
      Fourth Degree Hemorrhoidal Disease - a Cohort Study with 497 Patients].
AB  - Background Laser haemorrhoidoplasty (LHP) with the 1470 nm diode laser in
      minimally invasive surgery for advanced haemorrhoid disease has been studied with
      respect to clinical variables, such as pain and complications, and intraoperative
      characteristics such as mucopexia, number of treated knots and energy consumed
      per patient. The study also included patient satisfaction, symptom relevance and
      cost effectiveness. Patients and Methods Between November 2010 and November 2016,
      497 patients (age 55 +/- 14 years) were submitted to laser haemorrhoidoplasty
      with a 1470 nm diode laser in the centre for minimally invasive proctology in
      Siegen District Hospital. All operated patients were included in the study.
      Perioperative clinical and technical data up to 6 weeks and follow-up data up to
      6 months were analysed prospectively. Results The mean duration of operation was
      14 min (+/- 5.2). A mean of 2.7 knots of 2.7 size were treated per patient. The
      mean postoperative pain was 2.5/10 (VAS). Long-term symptom relevance was 86%,
      and patient satisfaction 91%. Complications occurred in 49 patients (9.9%):
      bleeding 1.8%, infection 1%, urine retention 1.8%, oedema/thrombosis/prolapse
      6.6%. 8.8% of patients suffered a relapse within 6 months. There were significant
      differences in pain on the day of the operation, and the parameters mucopexia, 3
      treated segments and energy level > 500 J (p < 0.05). Complications were more
      common when mucopexia was performed, with 3 treated knots and energy consumed per
      patient > 500 J. The only significant difference was for energy level > 500 J (p
      < 0.05). Conclusion LHP is a safe, low pain and minimally invasive surgical
      procedure with long-term good patient acceptance and satisfaction and is suited
      for routine work. The energy applied should be reduced to a minimum. Complication
      rates are largely comparable with those of other minimally invasive conventional
      methods. Additional prospective studies must be performed, particularly in
      comparison to the Parks method, which gives similar functional results. With
      circular confluent findings, LHP cannot replace stapler hemorrhoidopexia.

PMID- 29186746
TI  - [Interdisciplinary Acute Medical Rehabilitation after Sepsis - A Retrospective
      Analysis].
AB  - Background Surviving sepsis may have consequences of high impact for the
      patients' further life regarding functioning in mobility and activities of daily
      living, among other fields. Patients consecutively have a great need of
      rehabilitation interventions beginning with early mobilization in the Intensive
      Care Unit ICU. Acute medical rehabilitation is a concept of early rehabilitation
      still in the acute care hospital, normally beginning after a direct transferal
      from the ICU. Its aim is to improve the patients' functioning in mobility and
      activities of daily living (ADL) to enable further post-acute rehabilitation
      interventions. Methods In this retrospective analysis a sample of patients who
      received acute medical rehabilitation after surviving a sepsis or severe sepsis
      was followed. The study targeted the question if basic functions of mobility and
      ADL could be improved by acute medical rehabilitation. Furthermore, the need for
      aid supply was evaluated, as well as the type of discharge or transferal after
      acute care. Results The increase of mobility and ADL capability before and after
      acute medical rehabilitation was highly significant (p<0.001 each) and showed
      very large effect sizes (d=1.3, 1.4 respectively). Aid supply was organized for
      92% of patients. A majority of patients could receive consecutive post-acute
      rehabilitation after re-gaining function. Discussion The data shows the enormous
      gain in functioning that can be reached with an acute medical rehabilitation
      intervention after ICU treatment of sepsis.

PMID- 29186747
TI  - [Volume Growth of Inpatient Treatments for Spinal Disease - Analysis of German
      Nationwide Hospital Discharge Data from 2005 to 2014].
AB  - BACKGROUND: Marked volume growth of inpatient treatments for spinal disease has
      been observed since diagnosis related groups (DRG) were introduced as payment for
      inpatient services in Germany. This study aims to analyse this increase by
      population and stratified by types of treatment. MATERIAL AND METHODS: Using
      German nationwide hospital discharge data (DRG statistics), inpatient treatments
      for spinal disease with or without surgery were identified. Trends in case
      numbers were analysed from 2005 to 2014 with consideration of demographic
      changes, in order to explore which age groups and which types of treatment are
      affected by volume growth. RESULTS: In 2014 (2005), 289 000 (177 000) inpatient
      treatments with surgery and 463 000 (287 000) treatments without surgery were
      identified. After adjusting for demographic factors, treatments with and without
      surgery exhibited a relative volume growth of + 50%. This increase affected
      higher age groups and women, in particular. Depending on the type of treatment,
      very different degrees of volume growth were observed. For example, disc
      surgeries adjusted for demographic change increased by about + 5%, whereas spinal
      fusion and vertebral replacement surgeries, kypho-/vertebroplasties and
      decompression of the spine more than doubled. Within the non-surgically treated
      cases, local pain therapies of the spine increased after adjustment for
      demographic changes by about + 142%. The conservatively treated cases showed a
      demographically adjusted increase of + 22%. CONCLUSION: Apart from demographic
      changes, this analysis cannot resolve the underlying causes of volume growth in
      treatments for spinal disease. However, the stratified analysis of various
      subgroups may help to classify these developments in a more differentiated
      manner. The results may support a more targeted debate about potential over- or
      misallocation of inpatient services in this area.

PMID- 29186748
TI  - [Impact of microphone position on sound localization in cochlear implant users].
AB  - OBJECTIVE: The delivery of directional cues of a hearing device microphone are
      highly dependent on the position of the microphones. The aim of this work was the
      evaluation of different microphone positions with regard to the transmission of
      interaural time and level differences as well as the spectral characteristics and
      its impact on the localization abilities. METHODS: Head-related transfer
      functions of 30 subjects were measured with three different omnidirectional
      microphones at different positions: in the pinna (ITP), behind the ear (BTE), at
      the entrance of the ear canal (EEC). Sound localization abilities of 12 bilateral
      CI users was assessed for the microphone positions ITP and BTE. RESULTS: Only the
      microphone positions in the ear (ITP, EEC) could sample the spectral cues of the
      pinna. However, the positioning of the microphone inside of the pinna did not
      significantly improve sound localization abilities compared to BTE microphones.
      For sound incidence from rear significantly less front-back confusions were
      achieved with the microphone inside of the pinna. CONCLUSION: The microphone
      position in the pinna showed only a slight improvement in sound localization
      compared with BTE microphones in CI users. A precondition for better sound
      localization abilities is the improvement of the delivery of temporal and
      spectral fine structure cues in CI systems.

PMID- 29186749
TI  - [Microvascular reconstruction of the larynx following total laryngectomy].
AB  - Total laryngectomy still is a standard procedure for the treatment of advanced
      laryngeal or hypopharyngeal carcinoma. The unavoidable loss of voice may lead to
      serious impairments in quality of life. The most common technique of voice
      restoration is the tracheal-esophageal puncture combined with the application of
      a voice prosthesis. Laryngeal reconstruction with a radial forearm flap
      represents a possible surgical method of voice restoration. This study is a mono
      center retrospective analysis of patients receiving a so-called laryngoplasty
      after total laryngectomy between 2006 and 2015, focusing on long-term functional
      outcome and complications. 39 patients were included. Sufficient phonation was
      possible in 77 %, finger-free speaking was achieved in 62 %. Exclusion of
      irradiated patients revealed a rehabilitation rate of 91 %. The most common early
      complication was cervical hematoma in 15 %, whereas no loss of flap was assessed.
      Stenosis of the laryngoplasty was seen in 7 cases, mainly post-irradiation. The
      rate of successful voice restoration is equal in both, laryngoplasty and voice
      prosthesis patients. However, voice quality is better after surgical
      reconstruction. Complications induced by the voice prosthesis, which may be
      severe in some cases, were not seen in the study group. Furthermore, life-long
      support by an ENT specialist regarding voice prosthesis exchange is not
      necessary. Assuming correct choice of candidates, laryngoplasty is a sufficient
      method for voice restoration after laryngectomy.

PMID- 29186751
TI  - More on Ethics and Scholarship.

PMID- 29186752
TI  - A Novel Method to Improve the Anticancer Activity of Natural-Based Hydroxyapatite
      against the Liver Cancer Cell Line HepG2 Using Mesoporous Magnesia as a Micro
      Carrier.
AB  - Micro-carriers are the best known vehicles to transport different kinds of drugs
      to achieve high impact. In this study, mesoporous magnesium oxide has been
      harnessed as a micro-carrier to encapsulate the anticancer candidate drug natural
      based cubic hydroxyapatite (HAP). HAP@MgO composites with different HAP loading
      (0-60 wt %), were prepared by a hydrothermal treatment method using triethanol
      amine as a template. The characterization of the prepared composites were
      achieved by using XRD, Raman spectroscopy, FTIR and SEM. Characterization data
      confirm the formation of sphere-like structures of MgO containing HAP particles.
      It was observed that the size of the spheres increased with HAP loading up to 40
      wt %, then collapsed. Furthermore, the anticancer property of the prepared
      composites was evaluated against the HepG2 liver cancer cell line. The HAP@MgO
      composites exhibited higher activity than neat MgO or HAP. The 20 wt % of HAP was
      the optimum loading to control cell proliferation by inducing apoptosis.
      Apoptosis was determined by typical apoptotic bodies produced by the cell
      membrane.

PMID- 29186754
TI  - Portable Electronic Nose Based on Electrochemical Sensors for Food Quality
      Assessment.
AB  - The steady increase in global consumption puts a strain on agriculture and might
      lead to a decrease in food quality. Currently used techniques of food analysis
      are often labour-intensive and time-consuming and require extensive sample
      preparation. For that reason, there is a demand for novel methods that could be
      used for rapid food quality assessment. A technique based on the use of an array
      of chemical sensors for holistic analysis of the sample's headspace is called
      electronic olfaction. In this article, a prototype of a portable, modular
      electronic nose intended for food analysis is described. Using the SVM method, it
      was possible to classify samples of poultry meat based on shelf-life with 100%
      accuracy, and also samples of rapeseed oil based on the degree of thermal
      degradation with 100% accuracy. The prototype was also used to detect
      adulterations of extra virgin olive oil with rapeseed oil with 82% overall
      accuracy. Due to the modular design, the prototype offers the advantages of
      solutions targeted for analysis of specific food products, at the same time
      retaining the flexibility of application. Furthermore, its portability allows the
      device to be used at different stages of the production and distribution process.

PMID- 29186755
TI  - Climate Modelling Shows Increased Risk to Eucalyptus sideroxylon on the Eastern
      Coast of Australia Compared to Eucalyptus albens.
AB  - Aim: To identify the extent and direction of range shift of Eucalyptus
      sideroxylon and E. albens in Australia by 2050 through an ensemble forecast of
      four species distribution models (SDMs). Each was generated using four global
      climate models (GCMs), under two representative concentration pathways (RCPs).
      Location: Australia. Methods: We used four SDMs of (i) generalized linear model,
      (ii) MaxEnt, (iii) random forest, and (iv) boosted regression tree to construct
      SDMs for species E. sideroxylon and E. albens under four GCMs including (a) MRI
      CGCM3, (b) MIROC5, (c) HadGEM2-AO and (d) CCSM4, under two RCPs of 4.5 and 6.0.
      Here, the true skill statistic (TSS) index was used to assess the accuracy of
      each SDM. Results: Results showed that E. albens and E. sideroxylon will lose
      large areas of their current suitable range by 2050 and E. sideroxylon is
      projected to gain in eastern and southeastern Australia. Some areas were also
      projected to remain suitable for each species between now and 2050. Our modelling
      showed that E. sideroxylon will lose suitable habitat on the western side and
      will not gain any on the eastern side because this region is one the most heavily
      populated areas in the country, and the populated areas are moving westward. The
      predicted decrease in E. sideroxylon's distribution suggests that land managers
      should monitor its population closely, and evaluate whether it meets criteria for
      a protected legal status. Main conclusions: Both Eucalyptus sideroxylon and E.
      albens will be negatively affected by climate change and it is projected that E.
      sideroxylon will be at greater risk of losing habitat than E. albens.

PMID- 29186756
TI  - Robust Vehicle Detection in Aerial Images Based on Cascaded Convolutional Neural
      Networks.
AB  - Vehicle detection in aerial images is an important and challenging task.
      Traditionally, many target detection models based on sliding-window fashion were
      developed and achieved acceptable performance, but these models are time
      consuming in the detection phase. Recently, with the great success of
      convolutional neural networks (CNNs) in computer vision, many state-of-the-art
      detectors have been designed based on deep CNNs. However, these CNN-based
      detectors are inefficient when applied in aerial image data due to the fact that
      the existing CNN-based models struggle with small-size object detection and
      precise localization. To improve the detection accuracy without decreasing speed,
      we propose a CNN-based detection model combining two independent convolutional
      neural networks, where the first network is applied to generate a set of vehicle
      like regions from multi-feature maps of different hierarchies and scales. Because
      the multi-feature maps combine the advantage of the deep and shallow
      convolutional layer, the first network performs well on locating the small
      targets in aerial image data. Then, the generated candidate regions are fed into
      the second network for feature extraction and decision making. Comprehensive
      experiments are conducted on the Vehicle Detection in Aerial Imagery (VEDAI)
      dataset and Munich vehicle dataset. The proposed cascaded detection model yields
      high performance, not only in detection accuracy but also in detection speed.

PMID- 29186757
TI  - Nitrogen-Doped Carbon Quantum Dots as Fluorescent Probes for Sensitive and
      Selective Detection of Nitrite.
AB  - Nitrites are the upstream precursors of the carcinogenic nitrosamines, which are
      widely found in the natural environment and many food products. It is important
      to develop a simple and sensitive sensor for detecting nitrites. In this work, a
      fluorescence probe based on nitrogen-doped carbon quantum dots (N-CQDs) was
      developed for the sensitive and selective determination of nitrites. At pH 2, the
      fluorescence of N-CQDs can be selectively quenched by nitrite due to the fact N
      nitroso compounds can be formed in the reaction of amide groups with nitrous
      acid, which results in fluorescence static quenching. Under optimal conditions,
      fluorescence intensity quenching upon addition of nitrite gives a satisfactory
      linear relationship covering the linear range of 0.2-20 MUM, and the limit of
      detection (LOD) is 40 nM. Moreover, this method has been successfully applied to
      the determination of nitrites in tap water, which indicates its great potential
      for monitoring of nitrites in environmental samples.

PMID- 29186758
TI  - Simultaneous Determination of Multiple Classes of Hydrophilic and Lipophilic
      Components in Shuang-Huang-Lian Oral Liquid Formulations by UPLC-Triple
      Quadrupole Linear Ion Trap Mass Spectrometry.
AB  - The Shuang-Huang-Lian (SHL) oral liquid is a combined herbal prescription used in
      the treatment of acute upper respiratory tract infection, acute bronchitis and
      pneumonia. Multiple constituents are considered to be responsible for the
      therapeutic effects of SHL. However, the quantitation of the multi-components
      from multiple classes is still unsatisfactory because of the high complexity of
      constituents in SHL. In this study, an accurate, rapid, and specific UPLC-MS/MS
      method was established for simultaneous quantification of 18 compounds from
      multiple classes in SHL oral liquid formulations. Chromatographic separation was
      performed on a HSS T3 (1.8 MUm, 2.1 mm * 100 mm) column, using a gradient mobile
      phase system of 0.1% formic acid in acetonitrile and 0.1% formic acid in water at
      a flow rate of 0.2 mL.min-1; the run time was 23 min. The MS was operated in
      negative electrospray ionization (ESI-) for analysis of 18 compounds using
      multiple reaction monitoring (MRM) mode. UPLC-ESI--MRM-MS/MS method showed good
      linear relationships (R2 > 0.999), repeatability (RSD < 3%), precisions (RSD <
      3%) and recovery (84.03-101.62%). The validated method was successfully used to
      determine multiple classes of hydrophilic and lipophilic components in the SHL
      oral liquids. Finally, principal component analysis (PCA) was used to classify
      and differentiate SHL oral liquid samples attributed to different manufacturers
      of China. The proposed UPLC-ESI--MRM-MS/MS coupled with PCA has been elucidated
      to be a simple and reliable method for quality evaluation of SHL oral liquids.

PMID- 29186759
TI  - Effect of Two Different Doses of Vitamin D Supplementation on Metabolic Profiles
      of Insulin-Resistant Patients with Polycystic Ovary Syndrome.
AB  - This study was carried out to evaluate the effects of vitamin D supplementation
      on the metabolic profiles of insulin-resistant subjects with polycystic ovary
      syndrome (PCOS). This randomized double-blind, placebo-controlled trial was
      conducted on 90 insulin-resistant women with PCOS. Participants were randomly
      assigned to three groups to intake either 4000 IU of vitamin D or 1000 IU of
      vitamin D or placebo (n = 30 each group) daily for 12 weeks. Vitamin D
      supplementation (4000 IU), compared with vitamin D (1000 IU) and placebo, led to
      significant reductions in total testosterone (-0.2 +/- 0.2 vs. -0.1 +/- 0.6 and
      +0.1 +/- 0.2 ng/mL, respectively, p = 0.02), free androgen index (FAI) (-0.06 +/-
      0.12 vs. -0.02 +/- 0.12 and +0.004 +/- 0.04, respectively, p = 0.04), hirsutism (
      1.1 +/- 1.1 vs. -0.8 +/- 1.2 and -0.1 +/- 0.4, respectively, p = 0.001) and high
      sensitivity C-reactive protein (hs-CRP) (-0.7 +/- 1.4 vs. -0.5 +/- 0.9 and +0.5
      +/- 2.4 mg/L, respectively, p = 0.01). In addition, we found significant
      elevations in mean change of sex hormone-binding globulin (SHBG) (+19.1 +/- 23.0
      vs. +4.5 +/- 11.0 and +0.7 +/- 10.4 nmol/L, respectively, p < 0.001) and total
      antioxidant capacity (TAC) (+130 +/- 144 vs. +33 +/- 126 and -36 +/- 104 mmol/L,
      respectively, p < 0.001) in the high-dose vitamin D group compared with low-dose
      vitamin D and placebo groups. Overall, high-dose vitamin D administration for 12
      weeks to insulin-resistant women with PCOS had beneficial effects on total
      testosterone, SHBG, FAI, serum hs-CRP and plasma TAC levels compared with low
      dose vitamin D and placebo groups.

PMID- 29186753
TI  - Intrinsic Disorder in Proteins with Pathogenic Repeat Expansions.
AB  - Intrinsically disordered proteins and proteins with intrinsically disordered
      regions have been shown to be highly prevalent in disease. Furthermore, disease
      causing expansions of the regions containing tandem amino acid repeats often push
      repetitive proteins towards formation of irreversible aggregates. In fact, in
      disease-relevant proteins, the increased repeat length often positively
      correlates with the increased aggregation efficiency and the increased disease
      severity and penetrance, being negatively correlated with the age of disease
      onset. The major categories of repeat extensions involved in disease include poly
      glutamine and poly-alanine homorepeats, which are often times located in the
      intrinsically disordered regions, as well as repeats in non-coding regions of
      genes typically encoding proteins with ordered structures. Repeats in such non
      coding regions of genes can be expressed at the mRNA level. Although they can
      affect the expression levels of encoded proteins, they are not translated as
      parts of an affected protein and have no effect on its structure. However, in
      some cases, the repetitive mRNAs can be translated in a non-canonical manner,
      generating highly repetitive peptides of different length and amino acid
      composition. The repeat extension-caused aggregation of a repetitive protein may
      represent a pivotal step for its transformation into a proteotoxic entity that
      can lead to pathology. The goals of this article are to systematically analyze
      molecular mechanisms of the proteinopathies caused by the poly-glutamine and poly
      alanine homorepeat expansion, as well as by the polypeptides generated as a
      result of the microsatellite expansions in non-coding gene regions and to examine
      the related proteins. We also present results of the analysis of the prevalence
      and functional roles of intrinsic disorder in proteins associated with
      pathological repeat expansions.

PMID- 29186760
TI  - Effects of A 60 Hz Magnetic Field of Up to 50 milliTesla on Human Tremor and EEG:
      A Pilot Study.
AB  - Humans are surrounded by sources of daily exposure to power-frequency (60 Hz in
      North America) magnetic fields (MFs). Such time-varying MFs induce electric
      fields and currents in living structures which possibly lead to biological
      effects. The present pilot study examined possible extremely low frequency (ELF)
      MF effects on human neuromotor control in general, and physiological postural
      tremor and electroencephalography (EEG) in particular. Since the EEG cortical mu
      rhythm (8-12 Hz) from the primary motor cortex and physiological tremor are
      related, it was hypothesized that a 60 Hz MF exposure focused on this cortical
      region could acutely modulate human physiological tremor. Ten healthy volunteers
      (age: 23.8 +/- 4 SD) were fitted with a MRI-compatible EEG cap while exposed to
      11 MF conditions (60 Hz, 0 to 50 mTrms, 5 mTrms increments). Simultaneously,
      physiological tremor (recorded from the contralateral index finger) and EEG (from
      associated motor and somatosensory brain regions) were measured. Results showed
      no significant main effect of MF exposure conditions on any of the analyzed
      physiological tremor characteristics. In terms of EEG, no significant effects of
      the MF were observed for C1, C3, C5 and CP1 electrodes. However, a significant
      main effect was found for CP3 and CP5 electrodes, both suggesting a decreased mu
      rhythm spectral power with increasing MF flux density. This is however not
      confirmed by Bonferroni corrected pairwise comparisons. Considering both EEG and
      tremor findings, no effect of the MF exposure on human motor control was
      observed. However, MF exposure had a subtle effect on the mu-rhythm amplitude in
      the brain region involved in tactile perception. Current findings are to be
      considered with caution due to the small size of this pilot work, but they
      provide preliminary insights to international agencies establishing guidelines
      regarding electromagnetic field exposure with new experimental data acquired in
      humans exposed to high mT-range MFs.

PMID- 29186761
TI  - Characterization of a Sea Buckthorn Extract and Its Effect on Free and
      Encapsulated Lactobacillus casei.
AB  - Probiotics are bacteria that can provide health benefits to consumers and are
      suitable to be added to a variety of foods. In this research, viability of
      immobilized Lactobacillus casei in alginate with or without sea buckthorn lipid
      extract were studied during heat treatment and with an in vitro gastrointestinal
      model. The characterization of the lipid extract was also done using the UV-Vis
      spectrometry (UV-Vis), high-performance liquid chromatography photodiode array
      detection method (HPLC-PDA), gas chromatography coupled with mass spectrometry
      (GS-MS) and Cryo scanning electron microscopy (Cryo-SEM). During heat treatment,
      the entrapped probiotic cells proved high viability (>6 CFU log/g), even at
      temperatures above 50  degrees C. The rich in monounsaturated fatty acids sea
      buckthorn fraction improved the in vitro digestion passage regarding the
      probiotic viability. The survival of the probiotic cells was 15% higher after 2 h
      in the acidic medium of the simulated gastric fluid in the sample where L. casei
      was encapsulated with the sea buckthorn extract compared with the samples where
      no extract was added. Thus, this approach may be effective for the future
      development of probiotic-supplemented foods as foods with health welfare for the
      consumers.

PMID- 29186763
TI  - PTP1B Inhibitors from the Entomogenous Fungi Isaria fumosorosea.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of
      insulin receptor (IR) signaling and a potential drug target for the treatment of
      type II diabetes and other associated metabolic syndromes. Thus, small molecule
      inhibitors of PTP1B can be considered as an attractive approach for the design of
      new therapeutic agents of type II diabetes and cancer diseases. In a continuing
      search for new PTP1B inhibitors, a new tetramic acid possessing a rare
      pyrrolidinedione skeleton named fumosorinone A (1), together with five known ones
      2-6 were isolated from the entomogenous fungus Isaria fumosorosea. The structures
      of 2-6 were elucidated by extensive spectroscopic analysis. Fumosorinone A (1)
      and beauvericin (6) showed significant PTP1B inhibitory activity with IC50 value
      of 3.24 MUM and 0.59 MUM.

PMID- 29186762
TI  - Grip Strength as an Indicator of Health-Related Quality of Life in Old Age-A
      Pilot Study.
AB  - Over the last century life expectancy has increased dramatically nearly all over
      the world. This dramatic absolute and relative increase of the old aged people
      component of the population has influenced not only population structure but also
      has dramatic implications for the individuals and public health services. The aim
      of the present pilot study was to examine the impact of physical well-being
      assessed by hand grip strength and social factors estimated by social contact
      frequency on health-related quality of life among 22 men and 41 women ranging in
      age between 60 and 94 years. Physical well-being was estimated by hand grip
      strength, data concerning subjective wellbeing and health related quality of life
      were collected by personal interviews based on the WHOQOL-BREF questionnaires.
      Number of offspring and intergenerational contacts were not related significantly
      to health-related quality of life, while social contacts with non-relatives and
      hand grip strength in contrast had a significant positive impact on health
      related quality of life among old aged men and women. Physical well-being and in
      particular muscle strength-estimated by grip strength-may increase health-related
      quality of life and is therefore an important source for well-being during old
      age. Grip strength may be used as an indicator of health-related quality of life.

PMID- 29186764
TI  - Update on Phytochemistry and Pharmacology of Naturally Occurring Resveratrol
      Oligomers.
AB  - Resveratrol oligomers (REVs), a major class of stilbenoids, are biosynthesized by
      regioselective oxidative coupling of two to eight units of resveratrol monomer.
      Due to their unique structures and pleiotropic biological activities, natural
      product chemists are increasingly focusing on REVs in the last few decades. This
      study presents a detailed and thorough examination of REVs, including chemical
      structures, natural resources, and biological activities, during the period of
      2010-2017. Ninety-two new REVs compounds, including 39 dimers, 23 trimers, 13
      tetramers, six resveratrol monomers, six hexamers, four pentamers, and one
      octamer, have been reported from the families of Dipterocarpaceae, Paeoniaceae,
      Vitaceae, Leguminosae, Gnetaceae, Cyperaceae, Polygonaceae Gramineae, and
      Poaceae. Amongst these families, Dipterocarpaceae, with 50 REVs, accounts for the
      majority, and seven genera of Dipterocarpaceae are involved, including Vatica,
      Vateria, Shorea, Hopea, Neobalanocarpus, Dipterocarpus, and Dryobalanops. These
      REVs have shown a wide range of bioactivities. Pharmacological studies have
      mainly focused on potential efficacy on tumors, bacteria, Alzheimer's disease,
      cardiovascular diseases, and others. The information updated in this review might
      assist further research and development of novel REVs as potential therapeutic
      agents.

PMID- 29186765
TI  - To Group or Not to Group? Good Practice for Housing Male Laboratory Mice.
AB  - It is widely recommended to group-house male laboratory mice because they are
      'social animals', but male mice do not naturally share territories and aggression
      can be a serious welfare problem. Even without aggression, not all animals within
      a group will be in a state of positive welfare. Rather, many male mice may be
      negatively affected by the stress of repeated social defeat and subordination,
      raising concerns about welfare and also research validity. However, individual
      housing may not be an appropriate solution, given the welfare implications
      associated with no social contact. An essential question is whether it is in the
      best welfare interests of male mice to be group- or singly housed. This review
      explores the likely impacts-positive and negative-of both housing conditions,
      presents results of a survey of current practice and awareness of mouse behavior,
      and includes recommendations for good practice and future research. We conclude
      that whether group- or single-housing is better (or less worse) in any situation
      is highly context-dependent according to several factors including strain, age,
      social position, life experiences, and housing and husbandry protocols. It is
      important to recognise this and evaluate what is preferable from animal welfare
      and ethical perspectives in each case.

PMID- 29186767
TI  - A Microwave Microfluidic Sensor Based on a Dual-Mode Resonator for Dual-Sensing
      Applications.
AB  - In this paper, we propose a novel microwave microfluidic sensor with dual-sensing
      capability. The sensor is based on a dual-mode resonator that consists of a
      folded microstrip line loaded with interdigital lines and a stub at the plane of
      symmetry. Due to the specific configuration, the resonator exhibits two entirely
      independent resonant modes, which allows simultaneous sensing of two fluids using
      a resonance shift method. The sensor is designed in a multilayer configuration
      with the proposed resonator and two separated microfluidic channels-one
      intertwined with the interdigital lines and the other positioned below the stub.
      The circuit has been fabricated using low-temperature co-fired ceramics
      technology and its performance was verified through the measurement of its
      responses for different fluids in the microfluidic channels. The results confirm
      the dual-sensing capability with zero mutual influence as well as good overall
      performance. Besides an excellent potential for dual-sensing applications, the
      proposed sensor is a good candidate for application in mixing fluids and cell
      counting.

PMID- 29186766
TI  - Autophagy in Measles Virus Infection.
AB  - Autophagy is a biological process that helps cells to recycle obsolete cellular
      components and which greatly contributes to maintaining cellular integrity in
      response to environmental stress factors. Autophagy is also among the first lines
      of cellular defense against invading microorganisms, including viruses. The
      autophagic destruction of invading pathogens, a process referred to as xenophagy,
      involves cytosolic autophagy receptors, such as p62/SQSTM1 (Sequestosome 1) or
      NDP52/CALCOCO2 (Nuclear Dot 52 KDa Protein/Calcium Binding And Coiled-Coil Domain
      2), which bind to microbial components and target them towards growing
      autophagosomes for degradation. However, most, if not all, infectious viruses
      have evolved molecular tricks to escape from xenophagy. Many viruses even use
      autophagy, part of the autophagy pathway or some autophagy-associated proteins,
      to improve their infectious potential. In this regard, the measles virus,
      responsible for epidemic measles, has a unique interface with autophagy as the
      virus can induce multiple rounds of autophagy in the course of infection. These
      successive waves of autophagy result from distinct molecular pathways and seem
      associated with anti- and/or pro-measles virus consequences. In this review, we
      describe what the autophagy-measles virus interplay has taught us about both the
      biology of the virus and the mechanistic orchestration of autophagy.

PMID- 29186768
TI  - Monitoring the Wobbe Index of Natural Gas Using Fiber-Enhanced Raman
      Spectroscopy.
AB  - The fast and reliable analysis of the natural gas composition requires the
      simultaneous quantification of numerous gaseous components. To this end, fiber
      enhanced Raman spectroscopy is a powerful tool to detect most components in a
      single measurement using a single laser source. However, practical issues such as
      detection limit, gas exchange time and background Raman signals from the fiber
      material still pose obstacles to utilizing the scheme in real-world settings.
      This paper compares the performance of two types of hollow-core photonic crystal
      fiber (PCF), namely photonic bandgap PCF and kagome-style PCF, and assesses their
      potential for online determination of the Wobbe index. In contrast to bandgap
      PCF, kagome-PCF allows for reliable detection of Raman-scattered photons even
      below 1200 cm-1, which in turn enables fast and comprehensive assessment of the
      natural gas quality of arbitrary mixtures.

PMID- 29186769
TI  - Models in the Research Process of Psoriasis.
AB  - Psoriasis is an ancient, universal chronic skin disease with a significant
      geographical variability, with the lowest incidence rate at the equator,
      increasing towards the poles. Insights into the mechanisms responsible for
      psoriasis have generated an increasing number of druggable targets and molecular
      drugs. The development of relevant in vitro and in vivo models of psoriasis is
      now a priority and an important step towards its cure. In this review, we
      summarize the current cellular and animal systems suited to the study of
      psoriasis. We discuss the strengths and limitations of the various models and the
      lessons learned. We conclude that, so far, there is no one model that can meet
      all of the research needs. Therefore, the choice model system will depend on the
      questions being addressed.

PMID- 29186770
TI  - The Evaluation of Pro-Cognitive and Antiamnestic Properties of Berberine and
      Magnoflorine Isolated from Barberry Species by Centrifugal Partition
      Chromatography (CPC), in Relation to QSAR Modelling.
AB  - Civilization diseases associated with memory disorders are important health
      problems occurring due to a prolonged life span. The manuscript shows the results
      of an in vivo study targeting the emergence of two drug candidates with anti
      amnestic properties. The preceding quantitative structure-activity relationship
      (QSAR) studies provided information on the ability of berberine and magnoflorine
      to cross the blood-brain barrier (BBB). In the light of these findings, both
      compounds were purified from crude plant extracts of barberries: berberine-from
      Berberis siberica using a method published earlier, and magnoflorine-from
      Berberis cretica by centrifugal partition chromatography (solvent system: ethyl
      acetate:butanol:water-0.6:1.5:3 v/v/v). Both the compounds were evaluated for
      their memory enhancing and scopolamine inhibitory properties in an in vivo
      passive avoidance (PA) test on mice towards short-term and long-term memory.
      Cognition enhancing properties were observed at the following doses: 5 mg/kg
      (i.p.) for berberine and 20 mg/kg (i.p.) for magnoflorine. In addition, both the
      tested isoquinolines with the co-administered scopolamine were found to block
      long-term but not short-term memory impairment. No influence on the locomotor
      activity was observed for the tested doses. The results confirmed a marked
      central activity of magnoflorine and showed the necessity to lower the dosage of
      berberine. Optimized purification conditions have been elaborated for
      magnoflorine.

PMID- 29186771
TI  - Surface Acoustic Wave (SAW) for Chemical Sensing Applications of Recognition
      Layers.
AB  - Surface acoustic wave (SAW) resonators represent some of the most prominent
      acoustic devices for chemical sensing applications. As their frequency ranges
      from several hundred MHz to GHz, therefore they can record remarkably diminutive
      frequency shifts resulting from exceptionally small mass loadings. Their
      miniaturized design, high thermal stability and possibility of wireless
      integration make these devices highly competitive. Owing to these special
      characteristics, they are widely accepted as smart transducers that can be
      combined with a variety of recognition layers based on host-guest interactions,
      metal oxide coatings, carbon nanotubes, graphene sheets, functional polymers and
      biological receptors. As a result of this, there is a broad spectrum of SAW
      sensors, i.e., having sensing applications ranging from small gas molecules to
      large bio-analytes or even whole cell structures. This review shall cover from
      the fundamentals to modern design developments in SAW devices with respect to
      interfacial receptor coatings for exemplary sensor applications. The related
      problems and their possible solutions shall also be covered, with a focus on
      emerging trends and future opportunities for making SAW as established sensing
      technology.

PMID- 29186772
TI  - Correction: Watson, N.; et al. Effects of Low-Fat Diets Differing in Protein and
      Carbohydrate Content on Cardiometabolic Risk Factors during Weight Loss and
      Weight Maintenance in Obese Adults with Type 2 Diabetes. Nutrients 2016, 8, 289.
AB  - The authors request the following corrections to their paper [...].

PMID- 29186773
TI  - Metabolic Perturbations in a Bacillus subtilis clpP Mutant during Glucose
      Starvation.
AB  - Proteolysis is essential for all living organisms to maintain the protein
      homeostasis and to adapt to changing environmental conditions. ClpP is the main
      protease in Bacillus subtilis, and forms complexes with different Clp ATPases.
      These complexes play crucial roles during heat stress, but also in sporulation or
      cell morphology. Especially enzymes of cell wall-, amino acid-, and nucleic acid
      biosynthesis are known substrates of the protease ClpP during glucose starvation.
      The aim of this study was to analyze the influence of a clpP mutation on the
      metabolism in different growth phases and to search for putative new ClpP
      substrates. Therefore, B. subtilis 168 cells and an isogenic ?clpP mutant were
      cultivated in a chemical defined medium, and the metabolome was analyzed by a
      combination of 1H-NMR, HPLC-MS, and GC-MS. Additionally, the cell morphology was
      investigated by electron microscopy. The clpP mutant showed higher levels of most
      glycolytic metabolites, the intermediates of the citric acid cycle, amino acids,
      and peptidoglycan precursors when compared to the wild-type. A strong secretion
      of overflow metabolites could be detected in the exo-metabolome of the clpP
      mutant. Furthermore, a massive increase was observed for the teichoic acid
      metabolite CDP-glycerol in combination with a swelling of the cell wall. Our
      results show a recognizable correlation between the metabolome and the
      corresponding proteome data of B. subtilisclpP mutant. Moreover, our results
      suggest an influence of ClpP on Tag proteins that are responsible for teichoic
      acids biosynthesis.

PMID- 29186774
TI  - A Method for Measurement of Nonlinearity of Laser Interferometer Based on Optical
      Frequency Tuning.
AB  - A method for measuring the nonlinearity of laser interferometer using optical
      frequency tuning technique is presented in this paper. The basic principle of
      this method is to make the fractional part of an interference fringe change by
      tuning the laser frequency and determining the nonlinearity of interferometer by
      comparing the fractional fringe change measured by the interferometer to that
      calculated from the laser frequency change. An experimental interferometric
      system with a wavelength tunable laser source is set up and the nonlinearity of
      the interferometer is measured. Since it does not require the precise
      displacement mechanism to produce the optical path difference change, this method
      is more convenient to use and may achieve a higher accuracy than the conventional
      measurement methods. The nonlinearity of the arbitrary interferometric phase can
      be measured by changing the laser frequency with this method. Experiments results
      have shown that the repeatability of nonlinearity measurement is less than 0.2
      nm. This method can be applied to interferometry-based high precision dimensional
      measurements, such as coordinate measurement and displacement sensor calibration.

PMID- 29186775
TI  - Identifying the Epitope Regions of Therapeutic Antibodies Based on Structure
      Descriptors.
AB  - Therapeutic antibodies are widely used for disease detection and specific
      treatments. However, as an exogenous protein, these antibodies can be detected by
      the human immune system and elicit a response that can lead to serious illnesses.
      Therapeutic antibodies can be engineered through antibody humanization, which
      aims to maintain the specificity and biological function of the original
      antibodies, and reduce immunogenicity. However, the antibody drug effect is
      synchronously reduced as more exogenous parts are replaced by human antibodies.
      Hence, a major challenge in this area is to precisely detect the epitope regions
      in immunogenic antibodies and guide point mutations of exogenous antibodies to
      balance both humanization level and drug effect. In this article, the latest
      dataset of immunoglobulin complexes was collected from protein data bank (PDB) to
      discover the spatial features of immunogenic antibody. Furthermore, a series of
      structure descriptors were generated to characterize and distinguish epitope
      residues from non-immunogenic regions. Finally, a computational model was
      established based on structure descriptors, and results indicated that this model
      has the potential to precisely predict the epitope regions of therapeutic
      antibodies. With rapid accumulation of immunoglobulin complexes, this methodology
      could be used to improve and guide future antibody humanization and potential
      clinical applications.

PMID- 29186776
TI  - A Functionalized Tetrakis(4-Nitrophenyl)Porphyrin Film Optical Waveguide Sensor
      for Detection of H2S and Ethanediamine Gases.
AB  - The detection of hydrogen sulfide (H2S) and ethanediamine, toxic gases that are
      emitted from industrial processes, is important for health and safety. An optical
      sensor, based on the absorption spectrum of tetrakis(4-nitrophenyl)porphyrin
      (TNPP) immobilized in a Nafion membrane (Nf) and deposited onto an optical
      waveguide glass slide, has been developed for the detection of these gases.
      Responses to analytes were compared for sensors modified with TNPP and Nf-TNPP
      composites. Among them, Nf-TNPP exhibited significant responses to H2S and
      ethanediamine. The analytical performance characteristics of the Nf-TNPP-modified
      sensor were investigated and the response mechanism is discussed in detail. The
      sensor exhibited excellent reproducibilities, reversibilities, and selectivities,
      with detection limits for H2S and ethanediamine of 1 and 10 ppb, respectively,
      and it is a promising candidate for use in industrial sensing applications.

PMID- 29186778
TI  - Comparative Analysis of the Complete Chloroplast Genome of Four Known Ziziphus
      Species.
AB  - Ziziphus Mill. (Rhamnaceae) is comprised of about 170 species that are mainly
      distributed in tropical to subtropical regions, with few in the temperate zone.
      Several Ziziphus fruit tree species are important energy, nutrient, and medicinal
      resources for human populations, particularly for those living in rural regions.
      To date, limited genomic information is available for this genus. Here, we
      assembled the complete chloroplast genomes of four best known Ziziphus species,
      i.e., Ziziphus jujuba, Ziziphus acidojujuba, Ziziphus mauritiana, and Ziziphus
      spina-christi, based on the Illumina Paired-end sequencing method. The
      chloroplast genomes of the four Ziziphus species are all very similar to one
      another, and exhibit structural, gene content, and order characteristics that are
      similar to other flowering plants. The entire chloroplast genome encodes 113
      predicted unique genes (85 protein-coding genes, 8 rRNA, and 37 tRNA), 17 of
      which are duplicated in the inverted repeat regions. Rich single sequence repeats
      loci (217) were detected in Z. jujuba and 106 SSR loci, composed of A/T,
      displayed polymorphism across the four species by comparative genomic analysis.
      We found only four genes under positive selection between Z. jujuba and Z.
      acidojujuba, and two genes for Z. mauritiana vs. Z. spina-christi, respectively,
      while half of the 78 protein-coding genes experienced positive selection between
      the two groups. Phylogenetic analyses revealed that Ziziphus (Rhamnaceae) was
      sister to Elaeagnaceae, and the four species of Ziziphus were clustered into two
      groups (Z. jujuba and Z. acidojujuba, Z. mauritiana and Z. spina-christi). Our
      results provide genomic resources for intrageneric classifications of Ziziphus,
      and valuable genetic markers for investigating the population genetics and
      biogeography of closely related Ziziphus species.

PMID- 29186777
TI  - Clavine Alkaloids Gene Clusters of Penicillium and Related Fungi: Evolutionary
      Combination of Prenyltransferases, Monooxygenases and Dioxygenases.
AB  - The clavine alkaloids produced by the fungi of the Aspergillaceae and
      Arthrodermatacea families differ from the ergot alkaloids produced by Claviceps
      and Neotyphodium. The clavine alkaloids lack the extensive peptide chain
      modifications that occur in lysergic acid derived ergot alkaloids. Both clavine
      and ergot alkaloids arise from the condensation of tryptophan and
      dimethylallylpyrophosphate by the action of the dimethylallyltryptophan synthase.
      The first five steps of the biosynthetic pathway that convert tryptophan and
      dimethylallyl-pyrophosphate (DMA-PP) in chanoclavine-1-aldehyde are common to
      both clavine and ergot alkaloids. The biosynthesis of ergot alkaloids has been
      extensively studied and is not considered in this article. We focus this review
      on recent advances in the gene clusters for clavine alkaloids in the species of
      Penicillium, Aspergillus (Neosartorya), Arthroderma and Trychophyton and the
      enzymes encoded by them. The final products of the clavine alkaloids pathways
      derive from the tetracyclic ergoline ring, which is modified by late enzymes,
      including a reverse type prenyltransferase, P450 monooxygenases and
      acetyltransferases. In Aspergillus japonicus, a alpha-ketoglutarate and Fe2+
      dependent dioxygenase is involved in the cyclization of a festuclavine-like
      unknown type intermediate into cycloclavine. Related dioxygenases occur in the
      biosynthetic gene clusters of ergot alkaloids in Claviceps purpurea and also in
      the clavine clusters in Penicillium species. The final products of the clavine
      alkaloid pathway in these fungi differ from each other depending on the late
      biosynthetic enzymes involved. An important difference between clavine and ergot
      alkaloid pathways is that clavine producers lack the enzyme CloA, a P450
      monooxygenase, involved in one of the steps of the conversion of chanoclavine-1
      aldehyde into lysergic acid. Bioinformatic analysis of the sequenced genomes of
      the Aspergillaceae and Arthrodermataceae fungi showed the presence of clavine
      gene clusters in Arthroderma species, Penicillium roqueforti, Penicillium
      commune, Penicillium camemberti, Penicillium expansum, Penicillium steckii and
      Penicillium griseofulvum. Analysis of the gene clusters in several clavine
      alkaloid producers indicates that there are gene gains, gene losses and gene
      rearrangements. These findings may be explained by a divergent evolution of the
      gene clusters of ergot and clavine alkaloids from a common ancestral progenitor
      six genes cluster although horizontal gene transfer of some specific genes may
      have occurred more recently.

PMID- 29186779
TI  - The Effect of Red Palm Oil on Vitamin A Deficiency: A Meta-Analysis of Randomized
      Controlled Trials.
AB  - Red palm oil (RPO) has been investigated for preventing or alleviating vitamin A
      deficiency (VAD). Previous data has offered inconclusive and inconsistent results
      about the effects of RPO in patients with VAD. Our objective was to undertake a
      meta-analysis to assess the effects of RPO in preventing VAD in the population.
      After conducting a comprehensive literature search, nine randomized controlled
      trials (RCTs) were included. Overall, when trial results were pooled, the results
      indicated that RPO reduced the risk of VAD (relative risk (RR) (95% confidence
      interval (CI)) = 0.55 (0.37, 0.82), p = 0.003), increasedserum retinol levels in
      both children (p < 0.00001) and adults (p = 0.002), and increased beta-carotene
      levels (p = 0.01). However, RPO supplementation did not have a significant
      overall effect on serum alpha-carotene levels (p = 0.06), body weight (p = 0.45),
      and haemoglobin levels (p = 0.72). The results also showed that low level of PRO
      intake (<=8 g RPO) could increase serum retinol concentrations whereas PRO intake
      above 8 g did not lead to further increase of serum retinol concentrations. This
      meta-analysis demonstrated that RPO might be effective for preventing or
      alleviating VAD.

PMID- 29186780
TI  - Bullying and Cyberbullying: Their Legal Status and Use in Psychological
      Assessment.
AB  - Bullying and cyberbullying have severe psychological and legal consequences for
      those involved. However, it is unclear how or even if previous experience of
      bullying and cyberbullying is considered in mental health assessments.
      Furthermore, the relevance and effectiveness of current legal solutions has been
      debated extensively, resulting in a desire for a specific legislation. The
      purpose of this study is to investigate the psychological and legal components of
      bullying and cyberbullying. This is a qualitative research that includes
      interviews with five practitioner psychologists and four lawyers in the United
      Kingdom (UK). Thematic analysis revealed three main themes. One theme is related
      to the definition, characteristics, and impact of bullying and cyberbullying and
      the need for more discussion among the psychological and legal professions.
      Another theme is related to current professional procedures and the inclusion of
      questions about bullying and cyberbullying in psychological risk assessments. The
      third theme emphasised the importance of intervention through education. Two key
      messages were highlighted by the lawyers: ample yet problematic legislation
      exists, and knowledge will ensure legal success. The study recommends the
      necessity of performing revisions in the clinical psychological practices and
      assessments, and the legal policies regarding bullying and cyberbullying. In
      addition to improving legal success, this will reduce bullying prevalence rates,
      psychological distress, and psychopathology that can be comorbid or emerge as a
      result of this behaviour.

PMID- 29186781
TI  - The Heterologous Expression of the p22 RNA Silencing Suppressor of the Crinivirus
      Tomato Chlorosis Virus from Tobacco Rattle Virus and Potato Virus X Enhances
      Disease Severity but Does Not Complement Suppressor-Defective Mutant Viruses.
AB  - To counteract host antiviral RNA silencing, plant viruses express suppressor
      proteins that function as pathogenicity enhancers. The genome of the Tomato
      chlorosis virus (ToCV) (genus Crinivirus, family Closteroviridae) encodes an RNA
      silencing suppressor, the protein p22, that has been described as having one of
      the longest lasting local suppressor activities when assayed in Nicotiana
      benthamiana. Since suppression of RNA silencing and the ability to enhance
      disease severity are closely associated, we analyzed the effect of expressing p22
      in heterologous viral contexts. Thus, we studied the effect of the expression of
      ToCV p22 from viral vectors Tobacco rattle virus (TRV) and Potato virus X (PVX),
      and from attenuated suppressor mutants in N. benthamiana plants. Our results show
      that although an exacerbation of disease symptoms leading to plant death was
      observed in the heterologous expression of ToCV p22 from both viruses, only in
      the case of TRV did increased viral accumulation occur. The heterologous
      expression of ToCV p22 could not complement suppressor-defective mutant viruses.

PMID- 29186782
TI  - Forging a Frailty-Ready Healthcare System to Meet Population Ageing.
AB  - The beginning of the 21st century has seen health systems worldwide struggling to
      deliver quality healthcare amidst challenges posed by ageing populations. The
      increasing prevalence of frailty with older age and accompanying complexities in
      physical, cognitive, social and psychological dimensions renders the present
      modus operandi of fragmented, facility-centric, doctor-based, and illness
      centered care delivery as clearly unsustainable. In line with the public health
      framework for action in the World Health Organization's World Health and Ageing
      Report, meeting these challenges will require a systemic reform of healthcare
      delivery that is integrated, patient-centric, team-based, and health-centered.
      These reforms can be achieved through building partnerships and relationships
      that engage, empower, and activate patients and their support systems. To meet
      the challenges of population ageing, Singapore has reorganised its public
      healthcare into regional healthcare systems (RHSs) aimed at improving population
      health and the experience of care, and reducing costs. This paper will describe
      initiatives within the RHS frameworks of the National Health Group (NHG) and the
      Alexandra Health System (AHS) to forge a frailty-ready healthcare system across
      the spectrum, which includes the well healthy ("living well"), the well unhealthy
      ("living with illness"), the unwell unhealthy ("living with frailty"), and the
      end-of-life (EoL) ("dying well"). For instance, the AHS has adopted a community
      centered population health management strategy in older housing estates such as
      Yishun to build a geographically-based care ecosystem to support the self
      management of chronic disease through projects such as "wellness kampungs" and
      "share-a-pot". A joint initiative by the Lien Foundation and Khoo Teck Puat
      Hospital aims to launch dementia-friendly communities across the island by
      building a network comprising community partners, businesses, and members of the
      public. At the National Healthcare Group, innovative projects to address the
      needs of the frail elderly have been developed in the areas of: (a) admission
      avoidance through joint initiatives with long-term care facilities, nurse-led
      geriatric assessment at the emergency department and geriatric assessment
      clinics; (b) inpatient care, such as the Framework for Inpatient care of the
      Frail Elderly, orthogeriatric services, and geriatric surgical services; and (c)
      discharge to care, involving community transitional care teams and the
      development of community infrastructure for post-discharge support; and an
      appropriate transition to EoL care. In the area of EoL care, the National
      Strategy for Palliative Care has been developed to build an integrated system to:
      provide care for frail elderly with advance illnesses, develop advance care
      programmes that respect patients' choices, and equip healthcare professionals to
      cope with the challenges of EoL care.

PMID- 29186783
TI  - Altered Leukocyte Sphingolipid Pathway in Breast Cancer.
AB  - Sphingolipid metabolism pathway is essential in membrane homeostasis, and its
      dysfunction has been associated with favorable tumor microenvironment, disease
      progression, and chemotherapy resistance. Its major components have key functions
      on survival and proliferation, with opposing effects. We have profiled the
      components of the sphingolipid pathway on leukocytes of breast cancer (BC)
      patients undergoing chemotherapy treatment and without, including the five
      sphingosine 1-phosphate (S1P) receptors, the major functional genes, and
      cytokines, in order to better understand the S1P signaling in the immune cells of
      these patients. To the best of our knowledge, this is the first characterization
      of the sphingolipid pathway in whole blood of BC patients. Skewed gene profiles
      favoring high SPHK1 expression toward S1P production during BC development was
      observed, which was reversed by chemotherapy treatment, and reached similar
      levels to those found in healthy donors. Such levels were also correlated with
      high levels of TNF-alpha. Our data revealed an important role of the sphingolipid
      pathway in immune cells in BC with skewed signaling of S1P receptors, which
      favored cancer development even under chemotherapy, and may probably be a trigger
      of cancer resistance. Thus, these molecules must be considered as a target
      pathway for combined BC therapeutics.

PMID- 29186784
TI  - Species-Specific Inactivation of Triosephosphate Isomerase from Trypanosoma
      brucei: Kinetic and Molecular Dynamics Studies.
AB  - Human African Trypanosomiasis (HAT), a disease that provokes 2184 new cases a
      year in Sub-Saharan Africa, is caused by Trypanosoma brucei. Current treatments
      are limited, highly toxic, and parasite strains resistant to them are emerging.
      Therefore, there is an urgency to find new drugs against HAT. In this context, T.
      brucei depends on glycolysis as the unique source for ATP supply; therefore, the
      enzyme triosephosphate isomerase (TIM) is an attractive target for drug design.
      In the present work, three new benzimidazole derivatives were found as TbTIM
      inactivators (compounds 1, 2 and 3) with an I50 value of 84, 82 and 73 uM,
      respectively. Kinetic analyses indicated that the three molecules were selective
      when tested against human TIM (HsTIM) activity. Additionally, to study their
      binding mode in TbTIM, we performed a 100 ns molecular dynamics simulation of
      TbTIM-inactivator complexes. Simulations showed that the binding of compounds
      disturbs the structure of the protein, affecting the conformations of important
      domains such as loop 6 and loop 8. In addition, the physicochemical and drug-like
      parameters showed by the three compounds suggest a good oral absorption. In
      conclusion, these molecules will serve as a guide to design more potent
      inactivators that could be used to obtain new drugs against HAT.

PMID- 29186786
TI  - A Radar-Based Smart Sensor for Unobtrusive Elderly Monitoring in Ambient Assisted
      Living Applications.
AB  - Continuous in-home monitoring of older adults living alone aims to improve their
      quality of life and independence, by detecting early signs of illness and
      functional decline or emergency conditions. To meet requirements for technology
      acceptance by seniors (unobtrusiveness, non-intrusiveness, and privacy
      preservation), this study presents and discusses a new smart sensor system for
      the detection of abnormalities during daily activities, based on ultra-wideband
      radar providing rich, not privacy-sensitive, information useful for sensing both
      cardiorespiratory and body movements, regardless of ambient lighting conditions
      and physical obstructions (through-wall sensing). The radar sensing is a very
      promising technology, enabling the measurement of vital signs and body movements
      at a distance, and thus meeting both requirements of unobtrusiveness and
      accuracy. In particular, impulse-radio ultra-wideband radar has attracted
      considerable attention in recent years thanks to many properties that make it
      useful for assisted living purposes. The proposed sensing system, evaluated in
      meaningful assisted living scenarios by involving 30 participants, exhibited the
      ability to detect vital signs, to discriminate among dangerous situations and
      activities of daily living, and to accommodate individual physical
      characteristics and habits. The reported results show that vital signs can be
      detected also while carrying out daily activities or after a fall event (post
      fall phase), with accuracy varying according to the level of movements, reaching
      up to 95% and 91% in detecting respiration and heart rates, respectively.
      Similarly, good results were achieved in fall detection by using the micro-motion
      signature and unsupervised learning, with sensitivity and specificity greater
      than 97% and 90%, respectively.

PMID- 29186785
TI  - Screening In Vitro Targets Related to Diabetes in Herbal Extracts from Peru:
      Identification of Active Compounds in Hypericum laricifolium Juss. by Offline
      High-Performance Liquid Chromatography.
AB  - This study investigates in vitro targets related to diabetes in 30 herbal
      extracts from Peru, for the first time, using alpha-glucosidase, aldose reductase
      (AR) inhibitory assays and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging assays. Among the
      30 herbal extracts, Hypericum laricifolium Juss. (HL) was the herb which showed
      more than 50% inhibition in all assays, presenting 97.2 +/- 2.0%, 56.9 +/- 5.6%,
      81.9 +/- 2.5%, and 58.8 +/- 4.6% inhibition for the alpha-glucosidase, AR, DPPH,
      and ABTS assays, respectively. Finally, six bioactive compounds, namely,
      protocatechuic acid, chlorogenic acid, caffeic acid, kaempferol 3-O-glucuronide,
      quercetin, and kaempferol were identified in HL by offline high-performance
      liquid chromatography (HPLC). Quercetin exhibited the strongest inhibition in all
      enzyme assays and the strongest antioxidant activity. The results suggest that HL
      shows great potential for the complementary treatment of diabetes and its
      complications.

PMID- 29186787
TI  - Improving Pool Fencing Legislation in Queensland, Australia: Attitudes and Impact
      on Child Drowning Fatalities.
AB  - Four-sided, non-climbable pool fencing is an effective strategy for preventing
      children from drowning in home swimming pools. In 2009, the Queensland Government
      introduced legislation to improve the effectiveness of pool fencing. This study
      explores community attitudes towards the effectiveness of these legislative
      changes and examines child (<5 years) drowning deaths in pools. Data from the
      2011 Queensland Computer-Assisted Telephone Interviewing (CATI) Social Survey
      include results from questions related to pool ownership and pool fencing
      legislation. Fatal child drowning cases between 1 January 2005 and 31 December
      2015 were sourced from coronial data. Of the 1263 respondents, 26/100 households
      had a pool. A total of 58% believed tightening legislation would be effective in
      reducing child drowning deaths. Pool owners were more likely to doubt the
      effectiveness of legislation (p < 0.001) when compared to non-pool owners.
      Perceptions of effectiveness did not differ by presence of children under the age
      of five. There were 46 children who drowned in Queensland home pools (7.8/100,000
      pools with children residing in the residence/annum) between 2005 and 2015. While
      pool owners were less likely to think that tightening the legislation would be
      effective, the number of children drowning in home swimming pools declined over
      the study period. Drowning prevention agencies have more work to do to ensure
      that the most vulnerable (young children in houses with swimming pools) are
      protected.

PMID- 29186788
TI  - Neurotoxic Effects of Linalool and beta-Pinene on Tribolium castaneum Herbst.
AB  - Effective, ethical pest control requires the use of chemicals that are highly
      specific, safe, and ecofriendly. Linalool and beta-pinene occur naturally as
      major constituents of the essential oils of many plant species distributed
      throughout the world, and thus meet these requirements. These monoterpenes were
      tested as repellents against Tribolium castaneum, using the area preference
      method, after four hours of exposure and the effect transcriptional of genes
      associated with neurotransmission. Changes in gene expression of
      acetylcholinesterase (Ace1), GABA-gated anion channel splice variant 3a6a (Rdl),
      GABA-gated ion channel (Grd), glutamate-gated chloride channel (Glucl), and
      histamine-gated chloride channel 2 (Hiscl2) were assessed and the interaction
      with proteins important for the insect using in silico methods was also studied.
      For linalool and beta-pinene, the repellent concentration 50 (RC50) values were
      0.11 uL/cm2 and 0.03 uL/cm2, respectively. Both compounds induced overexpression
      of Hiscl2 gen in adult insects, and beta-pinene also promoted the overexpression
      of Grd and the Ace1 gene. However, beta-pinene and linalool had little potential
      to dock on computer-generated models for GABA-gated ion channel LCCH3, nicotinic
      acetylcholine receptor subunits alpha1 and alpha2, and putative
      octopamine/tyramine receptor proteins from T. castaneum as their respective
      binding affinities were marginal, and therefore the repellent action probably
      involved mechanisms other than direct interaction with these targets. Results
      indicated that beta-pinene was more potent than linalool in inducing insect
      repellency, and also had a greater capacity to generate changes in the expression
      of genes involved in neuronal transmission.

PMID- 29186789
TI  - Impact of Antibiotics on the Proliferation and Differentiation of Human Adipose
      Derived Mesenchymal Stem Cells.
AB  - Adipose tissue is a promising source of mesenchymal stem cells. Their potential
      to differentiate and regenerate other types of tissues may be affected by several
      factors. This may be due to in vitro cell-culture conditions, especially the
      supplementation with antibiotics. The aim of our study was to evaluate the
      effects of a penicillin-streptomycin mixture (PS), amphotericin B (AmB), a
      complex of AmB with copper (II) ions (AmB-Cu2+) and various combinations of these
      antibiotics on the proliferation and differentiation of adipose-derived stem
      cells in vitro. Normal human adipose-derived stem cells (ADSC, Lonza) were
      routinely maintained in a Dulbecco's Modified Eagle Medium (DMEM) that was either
      supplemented with selected antibiotics or without antibiotics. The ADSC that were
      used for the experiment were at the second passage. The effect of antibiotics on
      proliferation was analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) and sulforhodamine-B (SRB) tests.
      Differentiation was evaluated based on Alizarin Red staining, Oil Red O staining
      and determination of the expression of ADSC, osteoblast and adipocyte markers by
      real-time RT-qPCR. The obtained results indicate that the influence of
      antibiotics on adipose-derived stem cells depends on the duration of exposure and
      on the combination of applied compounds. We show that antibiotics alter the
      proliferation of cells and also promote natural osteogenesis, and adipogenesis,
      and that this effect is also noticeable in stimulated osteogenesis.

PMID- 29186790
TI  - Optimization of a Focusable and Rotatable Shear-Wave Periodic Permanent Magnet
      Electromagnetic Acoustic Transducers for Plates Inspection.
AB  - Due to the symmetry of conventional periodic-permanent-magnet electromagnetic
      acoustic transducers (PPM EMATs), two shear (SH) waves can be generated and
      propagated simultaneously in opposite directions, which makes the signal
      recognition and interpretation complicatedly. Thus, this work presents a new SH
      wave PPM EMAT design, rotating the parallel line sources to realize the wave beam
      focusing in a single-direction. The theoretical model of distributed line sources
      was deduced firstly, and the effects of some parameters, such as the inner coil
      width, adjacent line sources spacing and the angle between parallel line sources,
      on SH wave focusing and directivity were studied mainly with the help of 3D FEM.
      Employing the proposed PPM EMATs, some experiments are carried out to verify the
      reliability of FEM simulation. The results indicate that rotating the parallel
      line sources can strength the wave on the closing side of line sources,
      decreasing the inner coil width and the adjacent line sources spacing can improve
      the amplitude and directivity of signals excited by transducers. Compared with
      traditional PPM EMATs, both the capacity of unidirectional excitation and
      directivity of the proposed PPM EMATs are improved significantly.

PMID- 29186793
TI  - Connectivity and Topology Invariance in Self-Assembled and Halogen-Bonded Anionic
      (6,3)-Networks.
AB  - We report here that the halogen bond driven self-assembly of 1,3,5
      trifluorotriiodobenzene with tetraethylammonium and -phosphonium bromides affords
      1:1 co-crystals, wherein the mutual induced fit of the triiodobenzene derivative
      and the bromide anions (halogen bond donor and acceptors, respectively) elicits
      the potential of these two tectons to function as tritopic modules (6,3).
      Supramolecular anionic networks are present in the two co-crystals wherein the
      donor and the acceptor alternate at the vertexes of the hexagonal frames and
      cations are accommodated in the potential empty space encircled by the frames.
      The change of one component in a self-assembled multi-component co-crystal often
      results in a change in its supramolecular connectivity and topology. Our systems
      have the same supramolecular features of corresponding iodide analogues as the
      metric aspects seem to prevail over other aspects in controlling the self
      assembly process.

PMID- 29186794
TI  - Radioactive Cobalt(II) Removal from Aqueous Solutions Using a Reusable
      Nanocomposite: Kinetic, Isotherms, and Mechanistic Study.
AB  - A lignocellulose/montmorillonite (LMT) nanocomposite was prepared as a reusable
      adsorbent for cobalt(II) ions, and characterized by nitrogen (N2)
      adsorption/desorption isotherm, X-ray Diffraction (XRD), Scanning Electron
      Microscope (SEM), Transmission Electron Microscopy (TEM), and Fourier Transform
      Infrared Spectroscopy (FTIR). LMT exhibited efficient adsorption of cobalt ions
      (Co(II)), and the adsorbed Co(II) was readily desorbed by nitric acid (HNO3). All
      parameters affecting the adsorption and/or desorption of Co(II), including
      initial Co(II) concentration, pH value, temperature, HNO3 concentration, and
      time, were optimized. The kinetic data analysis showed that the adsorption
      followed the pseudo-second-order kinetic model and fit well into the Langmuir
      isotherm equation. Notably, the nanocomposite can be used four times without
      significantly losing adsorbent capability. The Energy-Dispersive X-ray (EDX) and
      FTIR spectra analysis also revealed that the adsorption mechanism may be mainly a
      chemical adsorption dominated process.

PMID- 29186792
TI  - Molecular Mechanisms of GPCR Signaling: A Structural Perspective.
AB  - G protein-coupled receptors (GPCRs) are cell surface receptors that respond to a
      wide variety of stimuli, from light, odorants, hormones, and neurotransmitters to
      proteins and extracellular calcium. GPCRs represent the largest family of
      signaling proteins targeted by many clinically used drugs. Recent studies shed
      light on the conformational changes that accompany GPCR activation and the
      structural state of the receptor necessary for the interactions with the three
      classes of proteins that preferentially bind active GPCRs, G proteins, G protein
      coupled receptor kinases (GRKs), and arrestins. Importantly, structural and
      biophysical studies also revealed activation-related conformational changes in
      these three types of signal transducers. Here, we summarize what is already known
      and point out questions that still need to be answered. Clear understanding of
      the structural basis of signaling by GPCRs and their interaction partners would
      pave the way to designing signaling-biased proteins with scientific and
      therapeutic potential.

PMID- 29186795
TI  - Hydroboration-Oxidation of (+/-)-(1alpha,3alpha,3abeta,6abeta)-1,2,3,3a,4,6a
      Hexahydro-1,3-pentalenedimethanol and Its O-Protected Derivatives: Synthesis of
      New Compounds Useful for Obtaining (iso)Carbacyclin Analogues and X-ray Analysis
      of the Products.
AB  - Hydroboration-oxidation of 2alpha,4alpha-dimethanol-1beta,5beta-bicyclo[3.3.0]oct
      6-en dibenzoate (1) gave alcohols 2 (symmetric) and 3 (unsymmetric) in ~60%
      yield, together with the monobenzoate diol 4a (37%), resulting from the reduction
      of the closer benzoate by the intermediate alkylborane. The corresponding alkene
      and dialdehyde gave only the triols 8 and 9 in ~1:1 ratio. By increasing the
      reaction time and the temperature, the isomerization of alkylboranes favours the
      un-symmetrical triol 9. The PDC oxidation of the alcohols gave cleanly the
      corresponding ketones 5 and 6 and the deprotection of the benzoate groups gave
      the symmetrical ketone 14, and the cyclic hemiketal 15, all in high yields. The
      ethylene ketals of the symmetrical ketones 11 and 13 were also obtained. The
      compounds 5, 6, 11, 13, 14 could be used for synthesis of new (iso)carbacyclin
      analogues. The structure of the compounds was established by NMR spectroscopy and
      confirmed by X-ray crystallography.

PMID- 29186796
TI  - Intuitionistic Linguistic Multiple Attribute Decision-Making with Induced
      Aggregation Operator and Its Application to Low Carbon Supplier Selection.
AB  - The main focus of this paper is to investigate the multiple attribute decision
      making (MADM) method under intuitionistic linguistic (IL) environment, based on
      induced aggregation operators and analyze possibilities for its application in
      low carbon supplier selection. More specifically, a new aggregation operator,
      called intuitionistic linguistic weighted induced ordered weighted averaging
      (ILWIOWA), is introduced to facilitate the IL information. Some of its desired
      properties are explored. A further generalization of the ILWIOWA, called
      intuitionistic linguistic generalized weighted induced ordered weighted averaging
      (ILGWIOWA), operator is developed. Furthermore, by employing the proposed
      operators, a MADM approach based on intuitionistic linguistic information is
      presented. Finally, an illustrative example concerning low carbon supplier
      selection and comparative analyses are conducted to demonstrate the effectiveness
      and practicality of the proposed approach.

PMID- 29186797
TI  - Carbon Nanofiber Cement Sensors to Detect Strain and Damage of Concrete Specimens
      Under Compression.
AB  - Cement composites with nano-additions have been vastly studied for their
      functional applications, such as strain and damage sensing. The capacity of a
      carbon nanofiber (CNF) cement paste has already been tested. However, this study
      is focused on the use of CNF cement composites as sensors in regular concrete
      samples. Different measuring techniques and humidity conditions of CNF samples
      were tested to optimize the strain and damage sensing of this material. In the
      strain sensing tests (for compressive stresses up to 10 MPa), the response
      depends on the maximum stress applied. The material was more sensitive at higher
      loads. Furthermore, the actual load time history did not influence the electrical
      response, and similar curves were obtained for different test configurations. On
      the other hand, damage sensing tests proved the capability of CNF cement
      composites to measure the strain level of concrete samples, even for loads close
      to the material's strength. Some problems were detected in the strain
      transmission between sensor and concrete specimens, which will require specific
      calibration of each sensor one attached to the structure.

PMID- 29186791
TI  - How do PrPSc Prions Spread between Host Species, and within Hosts?
AB  - Prion diseases are sub-acute neurodegenerative diseases that affect humans and
      some domestic and free-ranging animals. Infectious prion agents are considered to
      comprise solely of abnormally folded isoforms of the cellular prion protein known
      as PrPSc. Pathology during prion disease is restricted to the central nervous
      system where it causes extensive neurodegeneration and ultimately leads to the
      death of the host. The first half of this review provides a thorough account of
      our understanding of the various ways in which PrPSc prions may spread between
      individuals within a population, both horizontally and vertically. Many natural
      prion diseases are acquired peripherally, such as by oral exposure, lesions to
      skin or mucous membranes, and possibly also via the nasal cavity. Following
      peripheral exposure, some prions accumulate to high levels within the secondary
      lymphoid organs as they make their journey from the site of infection to the
      brain, a process termed neuroinvasion. The replication of PrPSc prions within
      secondary lymphoid organs is important for their efficient spread to the brain.
      The second half of this review describes the key tissues, cells and molecules
      which are involved in the propagation of PrPSc prions from peripheral sites of
      exposure (such as the lumen of the intestine) to the brain. This section also
      considers how additional factors such as inflammation and aging might influence
      prion disease susceptibility.

PMID- 29186798
TI  - Report of the International Society for Zinc Biology 5th Meeting, in
      Collaboration with Zinc-Net (COST Action TD1304)-UCLan Campus, Pyla, Cyprus.
AB  - From 18 to 22 June 2017, the fifth biennial meeting of the International Society
      for Zinc Biology was held in conjunction with the final dissemination meeting of
      the Network for the Biology of Zinc (Zinc-Net) at the University of Central
      Lancashire, Cyprus campus. The meeting attracted over 160 participants, had 17
      scientific symposia, 4 plenary speakers and 2 poster discussion sessions. In this
      report, we give an overview of the key themes of the meeting and some of the
      highlights from the scientific programme.

PMID- 29186799
TI  - Whole-Genome Re-Alignment Facilitates Development of Specific Molecular Markers
      for Races 1 and 4 of Xanthomonas campestris pv. campestris, the Cause of Black
      Rot Disease in Brassica oleracea.
AB  - Black rot, caused by Xanthomonas campestris pv. campestris (Xcc), is a seed borne
      disease of Brassicaceae. Eleven pathogenic races have been identified based on
      the phenotype interaction pattern of differential brassica cultivars inoculated
      with different strains. Race 1 and 4 are the two most frequent races found in
      Brassica oleracea crops. In this study, a PCR molecular diagnostic tool was
      developed for the identification of Xcc races 1 and 4 of this pathogen. Whole
      genomic sequences of races 1, 3, 4 and 9 and sequences of three other Xanthomonas
      pathovars/species (X. campestris pv. incanae (Xci), X. campestris pv. raphani
      (Xcr) and X.euvesicatoria (Xev) were aligned to identify variable regions among
      races. To develop specific markers for races 1 and 4, primers were developed from
      a region where sequences were dissimilar in other races. Sequence-characterized
      amplified regions (SCAR) and insertion or deletion of bases (InDel) were used to
      develop each specific set of primers. The specificity of the selected primers was
      confirmed by PCR tests using genomic DNA of seven different Xcc races, two
      strains of X. campestris pathovars and other species of bacteria. Bacterial
      samples of the races 1 and 4 isolates were collected from artificially inoculated
      cabbage leaves to conduct bio-PCR. Bio-PCR successfully detected the two Xcc
      isolates. By using our race-specific markers, a potential race 1 strain from the
      existing Korean Xcc collection was identified. The Xcc race 1 and 4-specific
      markers developed in this study are novel and can potentially be used for rapid
      detection of Xcc races through PCR.

PMID- 29186800
TI  - Social Determinants of Depression: The Intersections of Race, Gender, and
      Socioeconomic Status.
AB  - BACKGROUND: Despite the wealth of literature on social determinants of mental
      health, less is known about the intersection of these determinants. Using a
      nationally representative sample, this study aimed to study separate, additive,
      and multiplicative effects of race, gender, and SES on the risk of major
      depressive episode (MDE) among American adults. METHODS: National Survey of
      American Life (NSAL) included 3570 African Americans and 891 Whites. Race,
      gender, socioeconomic status (SES, household income, education, employment, and
      marital status) were independent variables. Twelve-month MDE was measured by the
      Composite International Diagnostic Interview (CIDI). A series of logistic
      regressions were used to analyze the data. RESULTS: In the pooled sample, race
      and household income, but not gender, education, employment, and marital status
      were associated with 12-month MDE. Gender interacted with the effects of income
      on MDE, suggesting that the association between household income and MDE is
      larger for women than men. In race by gender specific models that controlled for
      other SES indicators, high income was protective for White women, education was
      protective for African American women, and high income became a risk factor for
      African American men. High income did not show a risk effect for African American
      men in the absence of other SES indicators. CONCLUSIONS: Findings suggest that
      race, gender, and class interact on how SES indicators, such as education or
      income, become a protective or a risk factor for MDE among American Adults. When
      the outcome is MDE, White women benefit more from income, African American women
      gain from education, however, the residual effect of high income (above and
      beyond education, employment, and marital status) may become a risk factor for
      African American men.

PMID- 29186801
TI  - Epigenetic Basis of Cellular Senescence and Its Implications in Aging.
AB  - Cellular senescence is a tumor suppressive response that has become recognized as
      a major contributor of tissue aging. Senescent cells undergo a stable
      proliferative arrest that protects against neoplastic transformation, but acquire
      a secretory phenotype that has long-term deleterious effects. Studies are still
      unraveling the effector mechanisms that underlie these senescence responses with
      the goal to identify therapeutic interventions. Such effector mechanisms have
      been linked to the dramatic remodeling in the epigenetic and chromatin landscape
      that accompany cellular senescence. We discuss these senescence-associated
      epigenetic changes and their impact on the senescence phenotypes, notably the
      proliferative arrest and senescence associated secretory phenotype (SASP). We
      also explore possible epigenetic targets to suppress the deleterious effects of
      senescent cells that contribute towards aging.

PMID- 29186802
TI  - Bronchitis and Its Associated Risk Factors in First Nations Children.
AB  - Respiratory diseases, such as bronchitis and pneumonia, are common in First
      Nations children in Canada. The objectives are to determine prevalence and
      associated risk factors of bronchitis in children 6-17 years old residing in two
      reserve communities. The cross-sectional study was conducted in 2013 and children
      from two First Nations reserve communities participated. The outcome was ever
      presence/absence of bronchitis. Logistic regression analysis was conducted to
      examine the relationship between bronchitis and the individual and environmental
      factors. A total of 351 First Nations children participated in the study. The
      prevalence of bronchitis was 17.9%. While 86.6% had at least one parent who
      smoked, smoking inside home was 43.9%. Signs of mold and mildew in homes were
      high. Prevalence of houses with any damage caused by dampness was 42.2%, with
      44.2% of homes showing signs of mold or mildew. Significant predictors of
      increased risk of bronchitis were: being obese; having respiratory allergies;
      exposed to parental cigarette smoking; and signs of mold and mildew in the home.
      There are several modifiable risk factors that should be considered when
      examining preventive interventions for bronchitis including obesity, smoking
      exposure, and home mold or dampness.

PMID- 29186803
TI  - Effects of Different Types of Front-of-Pack Labelling Information on the
      Healthiness of Food Purchases-A Randomised Controlled Trial.
AB  - BACKGROUND: Front-of-pack nutrition labelling may support healthier packaged food
      purchases. Australia has adopted a novel Health Star Rating (HSR) system, but the
      legitimacy of this choice is unknown. OBJECTIVE: To define the effects of
      different formats of front-of-pack labelling on the healthiness of food purchases
      and consumer perceptions. DESIGN: Individuals were assigned at random to access
      one of four different formats of nutrition labelling-HSR, multiple traffic light
      labels (MTL), daily intake guides (DIG), recommendations/warnings (WARN)-or
      control (the nutrition information panel, NIP). Participants accessed nutrition
      information by using a smartphone application to scan the bar-codes of packaged
      foods, while shopping. The primary outcome was healthiness defined by the mean
      transformed nutrient profile score of packaged foods that were purchased over
      four weeks. RESULTS: The 1578 participants, mean age 38 years, 84% female
      recorded purchases of 148,727 evaluable food items. The mean healthiness of the
      purchases in the HSR group was non-inferior to MTL, DIG, or WARN (all p < 0.001
      at 2% non-inferiority margin). When compared to the NIP control, there was no
      difference in the mean healthiness of purchases for HSR, MTL, or DIG (all p >
      0.07), but WARN resulted in healthier packaged food purchases (mean difference
      0.87; 95% confidence interval 0.03 to 1.72; p = 0.04). HSR was perceived by
      participants as more useful than DIG, and easier to understand than MTL or DIG
      (all p < 0.05). Participants also reported the HSR to be easier to understand,
      and the HSR and MTL to be more useful, than NIP (all p < 0.03). CONCLUSIONS:
      These real-world data align with experimental findings and provide support for
      the policy choice of HSR. Recommendation/warning labels warrant further
      exploration, as they may be a stronger driver of healthy food purchases.

PMID- 29186804
TI  - Neonatal Nutrition Predicts Energy Balance in Young Adults Born Preterm at Very
      Low Birth Weight.
AB  - Epidemiological studies and animal models suggest that early postnatal nutrition
      and growth can influence adult health. However, few human studies have objective
      recordings of early nutrient intake. We studied whether nutrient intake and
      growth during the first 9 weeks after preterm birth with very low birth weight
      (VLBW, <1500 g) predict total energy intake, resting energy expenditure (REE),
      physical activity and food preferences in young adulthood. We collected daily
      nutritional intakes and weights during the initial hospital stay from hospital
      records for 127 unimpaired VLBW participants. At an average age 22.5 years, they
      completed a three-day food record and a physical activity questionnaire and
      underwent measurements of body composition (dual X-ray absorptiometry; n = 115
      with adequate data) and REE (n = 92 with adequate data). We used linear
      regression and path analysis to investigate associations between neonatal
      nutrient intake and adult outcomes. Higher energy, protein and fat intakes during
      the first three weeks of life predicted lower relative (=per unit lean body mass)
      energy intake and relative REE in adulthood, independent of other pre- and
      neonatal factors. In path analysis, total effects of early nutrition and growth
      on relative energy intake were mostly explained by direct effects of early life
      nutrition. A path mediated by early growth reached statistical significance only
      for protein intake. There were no associations of neonatal intakes with physical
      activity or food preferences in adulthood. As a conclusion, higher intake of
      energy and nutrients during first three weeks of life of VLBW infants predicts
      energy balance after 20 years. This association is partly mediated through
      postnatal growth.

PMID- 29186805
TI  - Is Antimicrobial Photodynamic Therapy Effective as an Adjunct to Scaling and Root
      Planing in Patients with Chronic Periodontitis? A Systematic Review.
AB  - The aim of this systematic review was to investigate whether antimicrobial
      photodynamic therapy (aPDT) as either a primary mode of treatment or an adjunct
      to non-surgical treatment was more effective than scaling and root planing (SRP)
      alone in treating chronic periodontitis in terms of clinical attachment level
      (CAL) gain and probing depth (PD) reduction. The focused question was developed
      using the Patient, Intervention, Comparison, and Outcome (PICO) format, and two
      authors independently searched the Medline, EMBASE, Cochrane Library, Web of
      Science, Google Scholar, and Scopus databases for relevant studies from January
      2008 to December 2016. Twenty studies included in this systematic review were
      randomized clinical trials (RCTs) or quasi-RCTs of aPDT compared to placebo, no
      intervention, or non-surgical treatment in an adult population. Basic study
      characteristics, photosensitizing agents and wavelengths used in aPDT, frequency
      of aPDT application, effect of aPDT on clinical parameters, antimicrobial effect
      of aPDT in chronic periodontitis, effect of immunological parameters following
      aPDT and patient-based outcome measures were collected from the studies. Although
      there was a wide range of heterogeneity in the included studied, they all
      indicated that aPDT has the potential to be an effective adjunct in the treatment
      of chronic periodontitis. Long-term, multicenter studies with larger sample sizes
      are needed before aPDT can be recommended as an effective treatment modality.

PMID- 29186806
TI  - The Silencing of Carotenoid beta-Hydroxylases by RNA Interference in Different
      Maize Genetic Backgrounds Increases the beta-Carotene Content of the Endosperm.
AB  - Maize (Zea mays L.) is a staple food in many parts of Africa, but the endosperm
      generally contains low levels of the pro-vitamin A carotenoid beta-carotene,
      leading to vitamin A deficiency disease in populations relying on cereal-based
      diets. However, maize endosperm does accumulate high levels of other carotenoids,
      including zeaxanthin, which is derived from beta-carotene via two hydroxylation
      reactions. Blocking these reactions could therefore improve the endosperm beta
      carotene content. Accordingly, we used RNA interference (RNAi) to silence the
      endogenous ZmBCH1 and ZmBCH2 genes, which encode two non-heme di-iron carotenoid
      beta-hydroxylases. The genes were silenced in a range of maize genetic
      backgrounds by introgressing the RNAi cassette, allowing us to determine the
      impact of ZmBCH1/ZmBCH2 silencing in diverse hybrids. The beta-carotene content
      of the endosperm increased substantially in all hybrids in which ZmBCH2 was
      silenced, regardless of whether or not ZmBCH1 was silenced simultaneously.
      However, the beta-carotene content did not change significantly in C17 hybrids
      (M7 * C17 and M13 * C17) compared to C17 alone, because ZmBCH2 is already
      expressed at negligible levels in the C17 parent. Our data indicate that ZmBCH2
      is primarily responsible for the conversion of beta-carotene to zeaxanthin in
      maize endosperm.

PMID- 29186807
TI  - The POZ/BTB and AT-Hook Containing Zinc Finger 1 (PATZ1) Transcription Regulator:
      Physiological Functions and Disease Involvement.
AB  - PATZ1 is a zinc finger protein, belonging to the POZ domain Kruppel-like zinc
      finger (POK) family of architectural transcription factors, first discovered in
      2000 by three independent groups. Since that time accumulating evidences have
      shown its involvement in a variety of biological processes (i.e., embryogenesis,
      stemness, apoptosis, senescence, proliferation, T-lymphocyte differentiation) and
      human diseases. Here we summarize these studies with a focus on the PATZ1
      emerging and controversial role in cancer, where it acts as either a tumor
      suppressor or an oncogene. Finally, we give some insight on clinical perspectives
      using PATZ1 as a prognostic marker and therapeutic target.

PMID- 29186808
TI  - Controlling the Molecular Weight of Lignosulfonates by an Alkaline Oxidative
      Treatment at Moderate Temperatures and Atmospheric Pressure: A Size-Exclusion and
      Reverse-Phase Chromatography Study.
AB  - The molecular weights of lignosulfonates (LSs) are modified by a rather simple
      process involving an alkaline oxidative treatment at moderate temperatures (70-90
      degrees C) and atmospheric pressure. Starting from LSs with an average molecular
      weight of 90,000 Da, and using such a treatment, one can prepare controlled
      molecular weight LSs in the range of 30,000 to 3500 Da based on the average mass
      molecular weight. The LS depolymerisation was monitored via reverse-phase and
      size-exclusion chromatography. It has been shown that the combination of O2, H2O2
      and Cu as a catalyst in alkaline conditions at 80  degrees C induces a high LS
      depolymerisation. The depolymerisation was systemically accompanied by a vanillin
      production, the yields of which reached 1.4 wt % (weight percentage on LS raw
      basis) in such conditions. Also, the average molecular weight and vanillin
      concentration were correlated and depended linearly on the temperature and
      reaction duration.

PMID- 29186809
TI  - Aptamer Bioinformatics.
AB  - Aptamers are short nucleic acid sequences capable of specific, high-affinity
      molecular binding. They are isolated via SELEX (Systematic Evolution of Ligands
      by Exponential Enrichment), an evolutionary process that involves iterative
      rounds of selection and amplification before sequencing and aptamer
      characterization. As aptamers are genetic in nature, bioinformatic approaches
      have been used to improve both aptamers and their selection. This review will
      discuss the advancements made in several enclaves of aptamer bioinformatics,
      including simulation of aptamer selection, fragment-based aptamer design,
      patterning of libraries, identification of lead aptamers from high-throughput
      sequencing (HTS) data and in silico aptamer optimization.

PMID- 29186810
TI  - Dynamic Mechanical Properties and Microstructure of Graphene Oxide Nanosheets
      Reinforced Cement Composites.
AB  - This paper presents an experimental investigation on the effect of uniformly
      dispersed graphene oxide (GO) nanosheets on dynamic mechanical properties of
      cement based composites prepared with recycled fine aggregate (RFA). Three
      different amounts of GO, 0.05%, 0.10%, and 0.20% in mass of cement, were used in
      the experiments. The visual inspections of GO nanosheets were also carried out
      after ultrasonication by transmission electron microscope (TEM) atomic force
      microscope (AFM), and Raman to characterize the dispersion effect of graphite
      oxide. Dynamic mechanical analyzer test showed that the maximum increased amount
      of loss factor and storage modulus, energy absorption was 125%, 53%, and 200%
      when compared to the control sample, respectively. The flexural and compressive
      strengths of GO-mortar increased up to 22% to 41.3% and 16.2% to 16.4% with 0.20
      wt % GO at 14 and 28 days, respectively. However the workability decreased by
      7.5% to 18.8% with 0.05% and 0.2% GO addition. Microstructural analysis with
      environmental scanning electron microscopy (ESEM)/backscattered mode (BSEM)
      showed that the GO-cement composites had a much denser structure and better
      crystallized hydration products, meanwhile mercury intrusion porosimetry (MIP)
      testing and image analysis demonstrated that the incorporation of GO in the
      composites can help in refining capillary pore structure and reducing the air
      voids content.

PMID- 29186811
TI  - Ascorbic Acid Attenuates Senescence of Human Osteoarthritic Osteoblasts.
AB  - The accumulation of senescent cells is implicated in the pathology of several age
      related diseases. While the clearance of senescent cells has been suggested as a
      therapeutic target for patients with osteoarthritis (OA), cellular senescence of
      bone-resident osteoblasts (OB) remains poorly explored. Since oxidative stress is
      a well-known inducer of cellular senescence, we here investigated the effect of
      antioxidant supplementation on the isolation efficiency, expansion,
      differentiation potential, and transcriptomic profile of OB from osteoarthritic
      subchondral bone. Bone chips were harvested from sclerotic and non-sclerotic
      regions of the subchondral bone of human OA joints. The application of 0.1 mM
      ascorbic acid-2-phosphate (AA) significantly increased the number of outgrowing
      cells and their proliferation capacity. This enhanced proliferative capacity
      showed a negative correlation with the amount of senescent cells and was
      accompanied by decreased expression of reactive oxygen species (ROS) in cultured
      OB. Expanded cells continued to express differentiated OB markers independently
      of AA supplementation and demonstrated no changes in their capacity to
      osteogenically differentiate. Transcriptomic analyses revealed that apoptotic,
      cell cycle-proliferation, and catabolic pathways were the main pathways affected
      in the presence of AA during OB expansion. Supplementation with AA can thus help
      to expand subchondral bone OB in vitro while maintaining their special cellular
      characteristics. The clearance of such senescent OB could be envisioned as a
      potential therapeutic target for the treatment of OA.

PMID- 29186812
TI  - Biotechnological Applications of Microbial (Per)chlorate Reduction.
AB  - While the microbial degradation of a chloroxyanion-based herbicide was first
      observed nearly ninety years ago, only recently have researchers elucidated the
      underlying mechanisms of perchlorate and chlorate [collectively, (per)chlorate]
      respiration. Although the obvious application of these metabolisms lies in the
      bioremediation and attenuation of (per)chlorate in contaminated environments, a
      diversity of alternative and innovative biotechnological applications has been
      proposed based on the unique metabolic abilities of dissimilatory (per)chlorate
      reducing bacteria (DPRB). This is fueled in part by the unique ability of these
      organisms to generate molecular oxygen as a transient intermediate of the central
      pathway of (per)chlorate respiration. This ability, along with other novel
      aspects of the metabolism, have resulted in a wide and disparate range of
      potential biotechnological applications being proposed, including enzymatic
      perchlorate detection; gas gangrene therapy; enhanced xenobiotic bioremediation;
      oil reservoir bio-souring control; chemostat hygiene control; aeration
      enhancement in industrial bioreactors; and, biogenic oxygen production for
      planetary exploration. While previous reviews focus on the fundamental science of
      microbial (per)chlorate reduction (for example see Youngblut et al., 2016), here,
      we provide an overview of the emerging biotechnological applications of
      (per)chlorate respiration and the underlying organisms and enzymes to
      environmental and biotechnological industries.

PMID- 29186813
TI  - Chemical Profiling and Bioactivity of Body Wall Lipids from Strongylocentrotus
      droebachiensis.
AB  - The lipids from gonads and polyhydroxynaphthoquinone pigments from body walls of
      sea urchins are intensively studied. However, little is known about the body wall
      (BW) lipids. Ethanol extract (55  degrees C) contained about equal amounts of
      saturated (SaFA) and monounsaturated fatty acids (MUFA) representing 60% of total
      fatty acids, with myristic, palmitic and eicosenoic acids as major SaFAs and
      MUFAs, respectively. Non-methylene-interrupted dienes (13%) were composed of
      eicosadienoic and docosadienoic acids. Long-chain polyunsaturated fatty acids (LC
      PUFA) included two main components, n6 arachidonic and n3 eicosapentaenoic acids,
      even with equal concentrations (15 MUg/mg) and a balanced n6/n3 PUFA ratio
      (0.86). The UPLC-ELSD analysis showed that a great majority of the lipids (80%)
      in the ethanolic extract were phosphatidylcholine (60 MUg/mg) and
      phosphatidylethanolamine (40 MUg/mg), while the proportion of neutral lipids
      remained lower than 20%. In addition, alkoxyglycerol derivatives-chimyl,
      selachyl, and batyl alcohols-were quantified. We have assumed that the mechanism
      of action of body wall lipids in the present study is via the inhibition of MAPK
      p38, COX-1, and COX-2. Our findings open the prospective to utilize this lipid
      fraction as a source for the development of drugs with anti-inflammatory
      activity.

PMID- 29186814
TI  - Alternative Splicing of L-type CaV1.2 Calcium Channels: Implications in
      Cardiovascular Diseases.
AB  - L-type Cav1.2 calcium channels are the major pathway for Ca2+ influx to initiate
      the contraction of smooth and cardiac muscles. Alteration of Cav1.2 channel
      function has been implicated in multiple cardiovascular diseases, such as
      hypertension and cardiac hypertrophy. Alternative splicing is a post
      transcriptional mechanism that expands Cav1.2 channel structures to modify
      function, pharmacological and biophysical property such as calcium/voltage
      dependent inactivation (C/VDI), or to influence its post-translational modulation
      by interacting proteins such as Galectin-1. Alternative splicing has generated
      functionally diverse Cav1.2 isoforms that can be developmentally regulated in the
      heart, or under pathophysiological conditions such as in heart failure. More
      importantly, alternative splicing of certain exons of Cav1.2 has been reported to
      be regulated by splicing factors such as RNA-binding Fox-1 homolog 1/2 (Rbfox
      1/2), polypyrimidine tract-binding protein (PTBP1) and RNA-binding motif protein
      20 (RBM20). Understanding how Cav1.2 channel function is remodelled in disease
      will provide better information to guide the development of more targeted
      approaches to discover therapeutic agents for cardiovascular diseases.

PMID- 29186815
TI  - Characterization of the Transcriptome and Gene Expression of Tetraploid Black
      Locust Cuttings in Response to Etiolation.
AB  - Etiolation (a process of growing plants in partial or complete absence of light)
      promotes adventitious root formation in tetraploid black locust (Robinia
      pseudoacacia L.) cuttings. We investigated the mechanism underlying how
      etiolation treatment promotes adventitious root formation in tetraploid black
      locust and assessed global transcriptional changes after etiolation treatment.
      Solexa paired-end sequencing of complementary DNAs (cDNAs) from control (non
      etiolated, NE) and etiolated (E) samples resulted in 107,564 unigenes. In total,
      52,590 transcripts were annotated and 474 transcripts (211 upregulated and 263
      downregulated) potentially involved in etiolation were differentially regulated.
      These genes were associated with hormone metabolism and response, photosynthesis,
      signaling pathways, and starch and sucrose metabolism. In addition, we also found
      significant differences of phytohormone contents, activity of following enzymes
      i.e., peroxidase, polyphenol oxidase and indole acetic acid oxidase between NE
      and E tissues during some cottage periods. The genes responsive to etiolation
      stimulus identified in this study will provide the base for further understanding
      how etiolation triggers adventitious roots formation in tetraploid black locus.

PMID- 29186816
TI  - The Geography of the Alzheimer's Disease Mortality in Spain: Should We Focus on
      Industrial Pollutants Prevention?
AB  - Alzheimer's disease (AD) has a high worldwide prevalence but little is known
      about its aetiology and risk factors. Recent research suggests environmental
      factors might increase AD risk. We aim to describe the association between AD
      mortality and the presence of highly polluting industry in small areas in Spain
      between 1999 and 2010. We calculated AD age-adjusted Standardized Mortality Ratio
      (SMR), stratified by sex, grouped by industrial pollution density, compared for
      each small area of Spain. In the small areas with the highest mortality, the SMR
      among women was at least 25% greater than the national average (18% in men). The
      distribution of AD mortality was generally similar to that of high industrial
      pollution (higher mortality in the north, the Mediterranean coast and in some
      southern areas). The risk of AD mortality among women was 140% higher (123% among
      men) in areas with the highest industrial density in comparison to areas without
      polluting industries. This study has identified a geographical pattern of small
      areas with higher AD mortality risk and an ecological positive association with
      the density of highly polluting industry. Further research is needed on the
      potential impact of this type of industry pollution on AD aetiology and
      mortality.

PMID- 29186817
TI  - Toxicity Assessment of Carbon Nanomaterials in Zebrafish during Development.
AB  - Carbon nanomaterials (CNMs) are increasingly employed in nanomedicine as carriers
      for intracellular transport of drugs, imaging probes, and therapeutics agents,
      thanks to their unique optical and physicochemical properties. However, a better
      understanding about the effects of CNMs on a vertebrate model at the whole animal
      level is required. In this study, we compare the toxicity of oxidized carbon nano
      onions (oxi-CNOs), oxidized carbon nano-horns (oxi-CNHs) and graphene oxide (GO)
      in zebrafish (Danio rerio). We evaluate the possible effects of these
      nanomaterials on zebrafish development by assessing different end-points and
      exposure periods.

PMID- 29186819
TI  - Photoactive Gel for Assisted Cleaning during Olive Mill Wastewater Membrane
      Microfiltration.
AB  - A photoactive gel has been fabricated on the surface of polyethylene membranes
      for enhancing the fouling resistance during olive mill wastewater treatment.
      Light and pH responsive materials have been introduced in the membrane surface
      through the build up of a layer-by-layer pattern, which is formed by
      photocatalytic nanoparticles and ionic polyelectrolytes. The best working
      conditions to contrast foulants adsorption have been explored and identified.
      Repulsive interfacial forces and assisted transfer of foulants to catalytic sites
      have been envisaged as crucial factors for contrasting the decline of the flux
      during microfiltration. Tests in submerged configuration have been implemented
      for six continuous hours under irradiation at two different pH conditions. As a
      result, a worthy efficiency of the photoactive gel has been reached when suitable
      chemical microenvironments have been generated along the shell side of the
      membranes. No additional chemical reagents or expensive back-flushing procedures
      have been necessary to further clean the membranes; rather, fast and reversible
      pH switches have been enough to remove residues, thereby preserving the integrity
      of the layer-by-layer (LBL) complex onto the membrane surface.

PMID- 29186818
TI  - Multipurpose HTS Coagulation Analysis: Assay Development and Assessment of
      Coagulopathic Snake Venoms.
AB  - Coagulation assays currently employed are often low throughput, require
      specialized equipment and/or require large blood/plasma samples. This study
      describes the development, optimization and early application of a generic low
      volume and high-throughput screening (HTS) assay for coagulation activity. The
      assay is a time-course spectrophotometric measurement which kinetically measures
      the clotting profile of bovine or human plasma incubated with Ca2+ and a test
      compound. The HTS assay can be a valuable new tool for coagulation diagnostics in
      hospitals, for research in coagulation disorders, for drug discovery and for
      venom research. A major effect following envenomation by many venomous snakes is
      perturbation of blood coagulation caused by haemotoxic compounds present in the
      venom. These compounds, such as anticoagulants, are potential leads in drug
      discovery for cardiovascular diseases. The assay was implemented in an integrated
      analytical approach consisting of reversed-phase liquid chromatography (LC) for
      separation of crude venom components in combination with parallel post-column
      coagulation screening and mass spectrometry (MS). The approach was applied for
      the rapid assessment and identification of profiles of haemotoxic compounds in
      snake venoms. Procoagulant and anticoagulant activities were correlated with
      accurate masses from the parallel MS measurements, facilitating the detection of
      peptides showing strong anticoagulant activity.

PMID- 29186820
TI  - Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved
      Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects
      (RIBE).
AB  - Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects
      with potential for a plethora of damages in adjacent non-irradiated tissue. The
      cascade of molecular events is initiated in response to the exposure to ionizing
      radiation (IR), something that may occur during diagnostic or therapeutic medical
      applications. In order to better investigate these complex response mechanisms,
      we employed a unified framework integrating statistical microarray analysis,
      signal normalization, and translational bioinformatics functional analysis
      techniques. This approach was applied to several microarray datasets from Gene
      Expression Omnibus (GEO) related to RIBE. The analysis produced lists of
      differentially expressed genes, contrasting bystander and irradiated samples
      versus sham-irradiated controls. Furthermore, comparative molecular analysis
      through BioInfoMiner, which integrates advanced statistical enrichment and
      prioritization methodologies, revealed discrete biological processes, at the
      cellular level. For example, the negative regulation of growth, cellular response
      to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description
      of the phenotypic landscape of RIBE. Our results provide a more solid
      understanding of RIBE cell-specific response patterns, especially in the case of
      high-LET radiations, like alpha-particles and carbon-ions.

PMID- 29186821
TI  - Bacterial Endophyte Colonization and Distribution within Plants.
AB  - The plant endosphere contains a diverse group of microbial communities. There is
      general consensus that these microbial communities make significant contributions
      to plant health. Both recently adopted genomic approaches and classical
      microbiology techniques continue to develop the science of plant-microbe
      interactions. Endophytes are microbial symbionts residing within the plant for
      the majority of their life cycle without any detrimental impact to the host
      plant. The use of these natural symbionts offers an opportunity to maximize crop
      productivity while reducing the environmental impacts of agriculture. Endophytes
      promote plant growth through nitrogen fixation, phytohormone production, nutrient
      acquisition, and by conferring tolerance to abiotic and biotic stresses.
      Colonization by endophytes is crucial for providing these benefits to the host
      plant. Endophytic colonization refers to the entry, growth and multiplication of
      endophyte populations within the host plant. Lately, plant microbiome research
      has gained considerable attention but the mechanism allowing plants to recruit
      endophytes is largely unknown. This review summarizes currently available
      knowledge about endophytic colonization by bacteria in various plant species, and
      specifically discusses the colonization of maize plants by Populus endophytes.

PMID- 29186823
TI  - The Subcellular Distribution of Alpha-Tocopherol in the Adult Primate Brain and
      Its Relationship with Membrane Arachidonic Acid and Its Oxidation Products.
AB  - The relationship between alpha-tocopherol, a known antioxidant, and
      polyunsaturated fatty acid (PUFA) oxidation, has not been directly investigated
      in the primate brain. This study characterized the membrane distribution of alpha
      tocopherol in brain regions and investigated the association between membrane
      alpha-tocopherol and PUFA content, as well as brain PUFA oxidation products.
      Nuclear, myelin, mitochondrial, and neuronal membranes were isolated using a
      density gradient from the prefrontal cortex (PFC), cerebellum (CER), striatum
      (ST), and hippocampus (HC) of adult rhesus monkeys (n = 9), fed a stock diet
      containing vitamin E (alpha-, gamma-tocopherol intake: ~0.7 umol/kg body
      weight/day, ~5 umol/kg body weight/day, respectively). alpha-tocopherol, PUFAs,
      and PUFA oxidation products were measured using high performance liquid
      chromatography (HPLC), gas chromatography (GC) and liquid chromatography-gas
      chromatography/mass spectrometry (LC-GC/MS) respectively. alpha-Tocopherol (ng/mg
      protein) was highest in nuclear membranes (p < 0.05) for all regions except HC.
      In PFC and ST, arachidonic acid (AA, ug/mg protein) had a similar membrane
      distribution to alpha-tocopherol. Total alpha-tocopherol concentrations were
      inversely associated with AA oxidation products (isoprostanes) (p < 0.05), but
      not docosahexaenoic acid oxidation products (neuroprostanes). This study reports
      novel data on alpha-tocopherol accumulation in primate brain regions and
      membranes and provides evidence that alpha-tocopherol and AA are similarly
      distributed in PFC and ST membranes, which may reflect a protective effect of
      alpha-tocopherol against AA oxidation.

PMID- 29186822
TI  - Venture from the Interior-Herpesvirus pUL31 Escorts Capsids from Nucleoplasmic
      Replication Compartments to Sites of Primary Envelopment at the Inner Nuclear
      Membrane.
AB  - Herpesviral capsid assembly is initiated in the nucleoplasm of the infected cell.
      Size constraints require that newly formed viral nucleocapsids leave the nucleus
      by an evolutionarily conserved vescular transport mechanism called nuclear
      egress. Mature capsids released from the nucleoplasm are engaged in a membrane
      mediated budding process, composed of primary envelopment at the inner nuclear
      membrane and de-envelopment at the outer nuclear membrane. Once in the cytoplasm,
      the capsids receive their secondary envelope for maturation into infectious
      virions. Two viral proteins conserved throughout the herpesvirus family, the
      integral membrane protein pUL34 and the phosphoprotein pUL31, form the nuclear
      egress complex required for capsid transport from the infected nucleus to the
      cytoplasm. Formation of the nuclear egress complex results in budding of membrane
      vesicles revealing its function as minimal virus-encoded membrane budding and
      scission machinery. The recent structural analysis unraveled details of the
      heterodimeric nuclear egress complex and the hexagonal coat it forms at the
      inside of budding vesicles to drive primary envelopment. With this review, I
      would like to present the capsid-escort-model where pUL31 associates with capsids
      in nucleoplasmic replication compartments for escort to sites of primary
      envelopment thereby coupling capsid maturation and nuclear egress.

PMID- 29186824
TI  - Investigating Exchange Bias and Coercivity in Fe3O4-gamma-Fe2O3 Core-Shell
      Nanoparticles of Fixed Core Diameter and Variable Shell Thicknesses.
AB  - We have carried out extensive measurements on novel Fe3O4-gamma-Fe2O3 core-shell
      nanoparticles of nearly similar core diameter (8 nm) and of various shell
      thicknesses of 1 nm (sample S1), 3 nm (sample S2), and 5 nm (sample S3). The
      structure and morphology of the samples were studied using X-ray diffraction
      (XRD), transmission electron microscopy (TEM), and selected area electron
      diffraction (SAED). The direct current (DC) magnetic measurements were carried
      out using a superconducting quantum interference device (SQUID). Exchange bias
      and coercivity were investigated at several temperatures where the applied field
      was varied between 3 and -3 T. Several key results are obtained, such as: (a) the
      complete absence of exchange bias effect in sample S3; (b) the occurrence of
      nonconventional exchange bias effect in samples S2 and S1; (c) the sign-change of
      exchange bias field in sample S2; (d) the monotonic increase of coercivity with
      temperature above 100 K in all samples; (e) the existence of a critical
      temperature (100 K) at which the coercivity is minimum; (f) the surprising
      suppression of coercivity upon field-cooling; and (g) the observation of
      coercivity at all temperatures, even at 300 K. The results are discussed and
      attributed to the existence of spin glass clusters at the core-shell interface.

PMID- 29186825
TI  - Experimental Comparison of Photothermal Conversion Efficiency of Gold
      Nanotriangle and Nanorod in Laser Induced Thermal Therapy.
AB  - An experimental comparison of the photothermal conversion efficiency (PCE) for
      gold nanotriangles (GNTs) and nanorods (GNRs) was carried out in the present
      work. The discrete dipole approximation method was applied to identify the
      spectral characteristic of GNTs and GNRs with different aspect ratios. On this
      basis, the PCE of GNTs and GNRs in photothermal therapy were compared
      theoretically. Afterwards, an in vitro experiment was adopted to investigate the
      thermal effect of porcine muscle induced by laser irradiation, with and without
      injected GNTs and GNRs. The influences of laser total power, nanoparticle
      concentration, and nanoparticle type were investigated. It was found that for the
      commonly-used wavelengths for photothermal therapy, the PCE of GNTs is higher
      than that of the GNRs. Furthermore, for GNRs loaded in tissue in vitro, high
      laser power and high concentration of nanoparticles leads to the degeneration and
      even carbonization of tissue. However, for the GNTs with the same situation
      (laser power, nanoparticle volume concentration, and heating time), it could lead
      to the tissue's evaporation instead of carbonization.

PMID- 29186826
TI  - Inhibition of Bacteria Associated with Wound Infection by Biocompatible Green
      Synthesized Gold Nanoparticles from South African Plant Extracts.
AB  - Unlike conventional physical and chemical methods, the biogenic synthesis of gold
      nanoparticles (GNPs) is considered a green and non-toxic approach to produce
      biocompatible GNPs that can be utilized in various biomedical applications. This
      can be achieved by using plant-derived phytochemicals to reduce gold salt into
      GNPs. Several green synthesized GNPs have been shown to have antibacterial
      effects, which can be applied in wound dressings to prevent wound infections.
      Therefore, the aim of this study is to synthesize biogenic GNPs from the South
      African Galenia africana and Hypoxis hemerocallidea plants extracts and evaluate
      their antibacterial activity, using the Alamar blue assay, against bacterial
      strains that are known to cause wound infections. Additionally, we investigated
      the toxicity of the biogenic GNPs to non-cancerous human fibroblast cells (KMST
      6) using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT)
      assay. In this paper, spherical GNPs, with particle sizes ranging from 9 to 27
      nm, were synthesized and fully characterized. The GNPs from H. hemerocallidea
      exhibited antibacterial activity against all the tested bacterial strains,
      whereas GNPs produced from G. africana only exhibited antibacterial activity
      against Pseudomonas aeruginosa. The GNPs did not show any significant toxicity
      towards KMST-6 cells, which may suggest that these nanoparticles can be safely
      applied in wound dressings.

PMID- 29186827
TI  - Eukaryotic Elongation Factor 2 Kinase (eEF2K) in Cancer.
AB  - Eukaryotic elongation factor 2 kinase (eEF2K) is a highly unusual protein kinase
      that negatively regulates the elongation step of protein synthesis. This step
      uses the vast majority of the large amount of energy and amino acids required for
      protein synthesis. eEF2K activity is controlled by an array of regulatory inputs,
      including inhibition by signalling through mammalian target of rapamycin complex
      1 (mTORC1). eEF2K is activated under conditions of stress, such as energy
      depletion or nutrient deprivation, which can arise in poorly-vascularised
      tumours. In many such stress conditions, eEF2K exerts cytoprotective effects. A
      growing body of data indicates eEF2K aids the growth of solid tumours in vivo.
      Since eEF2K is not essential (in mice) under 'normal' conditions, eEF2K may be a
      useful target in the treatment of solid tumours. However, some reports suggest
      that eEF2K may actually impair tumorigenesis in some situations. Such a dual role
      of eEF2K in cancer would be analogous to the situation for other pathways
      involved in cell metabolism, such as autophagy and mTORC1. Further studies are
      needed to define the role of eEF2K in different tumour types and at differing
      stages in tumorigenesis, and to assess its utility as a therapeutic target in
      oncology.

PMID- 29186828
TI  - Drug-Target Interaction Prediction through Label Propagation with Linear
      Neighborhood Information.
AB  - Interactions between drugs and target proteins provide important information for
      the drug discovery. Currently, experiments identified only a small number of drug
      target interactions. Therefore, the development of computational methods for drug
      target interaction prediction is an urgent task of theoretical interest and
      practical significance. In this paper, we propose a label propagation method with
      linear neighborhood information (LPLNI) for predicting unobserved drug-target
      interactions. Firstly, we calculate drug-drug linear neighborhood similarity in
      the feature spaces, by considering how to reconstruct data points from neighbors.
      Then, we take similarities as the manifold of drugs, and assume the manifold
      unchanged in the interaction space. At last, we predict unobserved interactions
      between known drugs and targets by using drug-drug linear neighborhood similarity
      and known drug-target interactions. The experiments show that LPLNI can utilize
      only known drug-target interactions to make high-accuracy predictions on four
      benchmark datasets. Furthermore, we consider incorporating chemical structures
      into LPLNI models. Experimental results demonstrate that the model with
      integrated information (LPLNI-II) can produce improved performances, better than
      other state-of-the-art methods. The known drug-target interactions are an
      important information source for computational predictions. The usefulness of the
      proposed method is demonstrated by cross validation and the case study.

PMID- 29186829
TI  - Inhibition by Commercial Aminoglycosides of Human Connexin Hemichannels Expressed
      in Bacteria.
AB  - In addition to gap junctional channels that mediate cell-to-cell communication,
      connexins form hemichannels that are present at the plasma membrane. Since
      hemichannels are permeable to small hydrophilic compounds, including metabolites
      and signaling molecules, their abnormal opening can cause or contribute to cell
      damage in disorders such as cardiac infarct, stroke, deafness, skin diseases, and
      cataracts. Therefore, hemichannels are potential pharmacological targets. A few
      aminoglycosides, well-known broad-spectrum antibiotics, have been shown to
      inhibit hemichannels. Here, we tested several commercially available
      aminoglycosides for inhibition of human connexin hemichannels using a cell-based
      bacterial growth complementation assay that we developed recently. We found that
      kanamycin A, kanamycin B, geneticin, neomycin, and paromomycin are effective
      inhibitors of hemichannels formed by connexins 26, 43, and 46 (Cx26, Cx43, and
      Cx46). Because of the >70 years of clinical experience with aminoglycosides and
      the fact that several of the aminoglycosides tested here have been used in
      humans, they are promising starting points for the development of effective
      connexin hemichannel inhibitors.

PMID- 29186831
TI  - Integrated Management of Residential Indoor Air Quality: A Call for Stakeholders
      in a Changing Climate.
AB  - A paradigm change in the management of environmental health issues has been
      observed in recent years: instead of managing specific risks individually, a
      holistic vision of environmental problems would assure sustainable solutions.
      However, concrete actions that could help translate these recommendations into
      interventions are lacking. This review presents the relevance of using an
      integrated indoor air quality management approach to ensure occupant health and
      comfort. At the nexus of three basic concepts (reducing contaminants at the
      source, improving ventilation, and, when relevant, purifying the indoor air),
      this approach can help maintain and improve indoor air quality and limit exposure
      to several contaminants. Its application is particularly relevant in a climate
      change context since the evolving outdoor conditions have to be taken into
      account during building construction and renovation. The measures presented
      through this approach target public health players, building managers, owners,
      occupants, and professionals involved in building design, construction,
      renovation, and maintenance. The findings of this review will help the various
      stakeholders initiate a strategic reflection on the importance of indoor air
      quality and climate change issues for existing and future buildings. Several new
      avenues and recommendations are presented to set the path for future research
      activities.

PMID- 29186830
TI  - The Genetic Basis of Psoriasis.
AB  - Psoriasis is widely regarded as a multifactorial condition which is caused by the
      interaction between inherited susceptibility alleles and environmental triggers.
      In the last decade, technological advances have enabled substantial progress in
      the understanding of disease genetics. Genome-wide association studies have
      identified more than 60 disease susceptibility regions, highlighting the
      pathogenic involvement of genes related to Th17 cell activation. This pathway has
      now been targeted by a new generation of biologics that have shown great efficacy
      in clinical trials. At the same time, the study of rare variants of psoriasis has
      identified interleukin (IL)-36 cytokines as important amplifiers of Th17
      signaling and promising targets for therapeutic intervention. Here, we review
      these exciting discoveries, which highlight the translational potential of
      genetic studies.

PMID- 29186832
TI  - The Prevalence of Vitamin A Deficiency in Chinese Children: A Systematic Review
      and Bayesian Meta-Analysis.
AB  - Vitamin A deficiency (VAD), a leading cause of preventable childhood blindness,
      has been recognized as an important public health problem in many developing
      countries. In this study, we conducted a systematic review to identify all
      population-based studies of VAD and marginal VAD (MVAD) in Chinese children
      published from 1990 onwards. Hierarchical Bayesian meta-regressions were
      performed to examine the effects of age, sex, setting and year on the prevalence
      of VAD and MVAD, separately. The estimated prevalence was applied to the Chinese
      pediatric population in the year 2015 to generate prevalence estimates of VAD and
      MVAD for defined age groups, with 95% credible intervals (CrIs). Fifty-four
      studies met the inclusion criteria. The prevalence of VAD and MVAD both decreased
      with increasing age, and rural children had a higher prevalence of VAD and MVAD
      than urban children. In 2015, the prevalence of VAD was 5.16% (95% CrI: 1.95
      12.64) and that of MVAD was 24.29% (95% CrI: 12.69-41.27) in Chinese children
      aged 12 years and under. VAD remains a public health problem in China. Efforts to
      reduce VAD in younger children are needed, especially for those in rural areas.

PMID- 29186833
TI  - Terpenoids and Phenylpropanoids in Ligularia duciformis, L. kongkalingensis, L.
      nelumbifolia, and L. limprichtii.
AB  - The diversity in root chemicals and evolutionally neutral DNA regions in the
      complex of Ligularia duciformis, L. kongkalingensis, and L. nelumbifolia (the
      d/k/n complex) was studied using eight samples collected in central and northern
      Sichuan Province of China. Cacalol (14) and epicacalone (15), rearranged
      eremophilanes, were isolated from the complex for the first time. Two new
      phenylpropanoids were also obtained. Seven of the eight samples produced
      phenylpropanoids and the other produced lupeol alone. Two of the seven samples
      also produced furanoeremophilanes or their derivatives and one produced
      oplopanes. The geographical distribution of the sesquiterpene-producing
      populations suggests that the production of sesquiterpenes evolved independently
      in separate regions. L. limprichtii collected in northern Sichuan was also
      analyzed and its chemical composition and the sequence of internal transcribed
      spacers (ITSs) in the ribosomal RNA gene cluster were found to be similar to that
      in the d/k/n complex and L. yunnanensis, which are morphologically similar.

PMID- 29186834
TI  - Urinary Phthalate Concentrations in Mothers and Their Children in Ireland:
      Results of the DEMOCOPHES Human Biomonitoring Study.
AB  - Background: Phthalates are chemicals which are widespread in the environment.
      Although the impacts on health of such exposure are unclear, there is evidence of
      a possible impact on the incidence of a diverse range of diseases. Monitoring of
      human exposure to phthalates is therefore important. This study aimed to
      determine the extent of phthalate exposure among mothers and their children in
      both rural and urban areas in Ireland, and to identify factors associated with
      elevated concentrations. It formed part of the 'Demonstration of a study to Co
      ordinate and Perform Human Biomonitoring on a European Scale' (DEMOCOPHES) pilot
      biomonitoring study. Methods: the concentration of phthalate metabolites were
      determined from a convenience sample of 120 mother/child pairs. The median age of
      the children was 8 years. A questionnaire was used to collect information
      regarding lifestyle and environmental conditions of the children and mothers.
      Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and
      international comparability of results. Results: Phthalate metabolites were
      detected in all of the samples from both children and mothers. Concentrations
      were significantly higher in respondents from families with lower educational
      attainment and in those exposed to such items as polyvinyl chloride (PVC), fast
      food and personal care products (PCP). Conclusions: The study demonstrates that
      human biomonitoring for assessing exposure to phthalates can be undertaken in
      Ireland and that the exposure of the population is widespread. Further work will
      be necessary before the consequences of this exposure are understood.

PMID- 29186835
TI  - School Gardens: A Qualitative Study on Implementation Practices.
AB  - School gardens have beneficial effects on children's dietary behaviors but
      information on its implementation is scarce. The current study aimed to gain
      insight in implementation practices of school gardens and in perceptions of key
      members and children towards a school garden. We conducted twelve interviews
      involving 14 key members and five focus groups with 38 children from fifth to
      sixth grade (10-13 years old) in four primary schools in Ghent (Flanders,
      Belgium). We analyzed the interviews and focus groups in NVivo, using thematic
      analysis. School gardens were mainly initiated to involve children in nature, not
      to improve vegetable consumption. Participants were positive about having a
      school garden, experienced facilitating factors (e.g., adaptability of the
      garden, having a person responsible for the garden), but also various barriers
      (e.g., difficulties with startup, maintenance during summer holidays and
      integration in the school curriculum) and suggested some solutions (e.g.,
      involving external organizations and parents, expanding the garden) and
      motivating factors for children (e.g., colorful plants, use of gloves). In order
      to improve implementation and to contribute to children's health, future school
      gardening projects should take the recommendations of key members and children
      into account.

PMID- 29186836
TI  - Autonomous Shepherding Behaviors of Multiple Target Steering Robots.
AB  - This paper presents a distributed coordination methodology for multi-robot
      systems, based on nearest-neighbor interactions. Among many interesting tasks
      that may be performed using swarm robots, we propose a biologically-inspired
      control law for a shepherding task, whereby a group of external agents drives
      another group of agents to a desired location. First, we generated sheep-like
      robots that act like a flock. We assume that each agent is capable of measuring
      the relative location and velocity to each of its neighbors within a limited
      sensing area. Then, we designed a control strategy for shepherd-like robots that
      have information regarding where to go and a steering ability to control the
      flock, according to the robots' position relative to the flock. We define several
      independent behavior rules; each agent calculates to what extent it will move by
      summarizing each rule. The flocking sheep agents detect the steering agents and
      try to avoid them; this tendency leads to movement of the flock. Each steering
      agent only needs to focus on guiding the nearest flocking agent to the desired
      location. Without centralized coordination, multiple steering agents produce an
      arc formation to control the flock effectively. In addition, we propose a new
      rule for collecting behavior, whereby a scattered flock or multiple flocks are
      consolidated. From simulation results with multiple robots, we show that each
      robot performs actions for the shepherding behavior, and only a few steering
      agents are needed to control the whole flock. The results are displayed in maps
      that trace the paths of the flock and steering robots. Performance is evaluated
      via time cost and path accuracy to demonstrate the effectiveness of this
      approach.

PMID- 29186837
TI  - Systematic Review and Meta-Analysis of Human Skin Diseases Due to Particulate
      Matter.
AB  - This study investigated the effects of particulate matter (PM) on human skin
      diseases by conducting a systematic review of existing literature and performing
      a meta-analysis. It considered articles reporting an original effect of PM on
      human skin. From among 918 articles identified, 13 articles were included for
      further consideration after manual screening of the articles resulted in the
      exclusion of articles that did not contain data, review articles, editorials, and
      also articles in languages other than English. Random-effects models and forest
      plots were used to estimate the effect of PM on the skin by Meta-Disc analysis.
      According to people's reports of exposure and negative skin effects (atopic
      dermatitis (AD), eczema, and skin aging, etc.) due to air pollution, the summary
      relative risk (odds ratio) of PM10 was determined to be 0.99 (95% confidence
      interval (CI) 0.89-1.11) whereas PM2.5 was determined to be 1.04 (95% CI 0.96
      1.12). Simultaneously, there was a different extent of impact between PM10 and
      PM2.5 on atopic dermatitis (AD) for those of young age: the odds ratio of PM10
      and PM2.5 were 0.96 (95% CI 0.83-1.11; I2 = 62.7%) and 1.05 (95% CI 0.95-1.16; I2
      = 46%), respectively. Furthermore, the results suggest an estimated increase of
      disease incidence per 10 MUg/m3 PM of 1.01% (0.08-2.05) due to PM10 and 1.60%
      (0.45-2.82) due to PM2.5. Following the results, PM10 and PM2.5 are associated
      with increased risks of human skin diseases, especially AD, whose risk is higher
      in infants and school children. With its smaller size and a high concentration of
      metals, PM2.5 is more closely related to AD in younger people, compared to PM10.

PMID- 29186838
TI  - Role of MicroRNAs in TGF-beta Signaling Pathway-Mediated Pulmonary Fibrosis.
AB  - Pulmonary fibrosis is the most common form of interstitial lung disease. The
      transforming growth factor-beta (TGF-beta) signaling pathway is extensively
      involved in the development of pulmonary fibrosis by inducing cell
      differentiation, migration, invasion, or hyperplastic changes. Accumulating
      evidence indicates that microRNAs (miRNAs) are dysregulated during the initiation
      of pulmonary fibrosis. miRNAs are small noncoding RNAs functioning as negative
      regulators of gene expression at the post-transcriptional level. A number of
      miRNAs have been reported to regulate the TGF-beta signaling pathway and
      consequently affect the process of pulmonary fibrosis. A better understanding of
      the pro-fibrotic role of the TGF-beta signaling pathway and relevant miRNA
      regulation will shed light on biomedical research of pulmonary fibrosis. This
      review summarizes the current knowledge of miRNAs regulating the TGF-beta
      signaling pathway with relevance to pulmonary fibrosis.

PMID- 29186839
TI  - LSPR Coupling and Distribution of Interparticle Distances between Nanoparticles
      in Hydrogel on Optical Fiber End Face.
AB  - We report on a new localized surface plasmon resonance (LSPR)-based optical fiber
      (OF) architecture with a potential in sensor applications. The LSPR-OF system is
      fabricated by immobilizing gold nanoparticles (GNPs) in a hydrogel droplet
      polymerized on the fiber end face. This design has several advantages over
      earlier designs. It dramatically increase the number nanoparticles (NP) available
      for sensing, it offers precise control over the NP density, and the NPs are
      positioned in a true 3D aqueous environment. The OF-hydrogel design is also
      compatible with low-cost manufacturing. The LSPR-OF platform can measure
      volumetric changes in a stimuli-responsive hydrogel or measure binding to
      receptors on the NP surface. It can also be used as a two-parameter sensor by
      utilizing both effects. We present results from proof-of-concept experiments
      exploring the properties of LSPR and interparticle distances of the GNP-hydrogel
      OF design by characterizing the distribution of distances between NPs in the
      hydrogel, the refractive index of the hydrogel and the LSPR attributes of peak
      position, amplitude and linewidth for hydrogel deswelling controlled with pH
      solutions.

PMID- 29186840
TI  - Foodborne Norovirus State of Affairs in the EU Rapid Alert System for Food and
      Feed.
AB  - The European Union Rapid Alert System for Food and Feed (EU RASFF) database is an
      invaluable instrument for analyzing notifications involving norovirus in food.
      The aim of this work was to carry out a thorough research of the alert and border
      rejection notifications submitted in the RASFF database from its onset until 31
      August 2017. Some conclusions of interest were: (i) Denmark, France, Italy, the
      Netherlands and Norway have contributed the majority of alert notifications as
      notifying countries, (ii) France and Serbia have been cited more often in alert
      notifications as countries of origin, (iii) Italy and Spain have submitted the
      majority of border rejection notifications, (iv) Third Countries implicated more
      frequently in border rejection notifications for norovirus in bivalve molluscs
      were Vietnam and Tunisia, whereas in fruits and vegetables were China and Serbia,
      (v) "risk dispersion" from norovirus-contaminated food was narrow since, in just
      over half of all alert notifications and all of the border rejection
      notifications, only up to three countries were involved, and (vi) both raw
      (oysters and berries) and cooked (mussels) food products can present a health
      risk to consumers. The information retrieved from the RASFF database on norovirus
      contaminated food could prove helpful in the planning of future norovirus risk
      analysis endeavors.

PMID- 29186841
TI  - Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex
      Vivo Model of Proton Radiation Damage.
AB  - Radiation therapy for the treatment of thoracic malignancies has improved
      significantly by directing of the proton beam in higher doses on the targeted
      tumor while normal tissues around the tumor receive much lower doses.
      Nevertheless, exposure of normal tissues to protons is known to pose a
      substantial risk in long-term survivors, as confirmed by our work in space
      relevant exposures of murine lungs to proton radiation. Thus, radioprotective
      strategies are being sought. We established that LGM2605 is a potent protector
      from radiation-induced lung toxicity and aimed in the current study to extend the
      initial findings of space-relevant, proton radiation-associated late lung damage
      in mice by looking at acute changes in human lung. We used an ex vivo model of
      organ culture where tissue slices of donor living human lung were kept in culture
      and exposed to proton radiation. We exposed donor human lung precision-cut lung
      sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and
      evaluated them 30 min and 24 h later for gene expression changes relevant to
      inflammation, oxidative stress, and cell cycle arrest, and determined radiation
      induced senescence, inflammation, and oxidative tissue damage. We identified an
      LGM2605-mediated reduction of proton radiation-induced cellular senescence and
      associated cell cycle changes, an associated proinflammatory phenotype, and
      associated oxidative tissue damage. This is a first report on the effects of
      proton radiation and of the radioprotective properties of LGM2605 on human lung.

PMID- 29186843
TI  - A 2.5D Map-Based Mobile Robot Localization via Cooperation of Aerial and Ground
      Robots.
AB  - Recently, there has been increasing interest in studying the task coordination of
      aerial and ground robots. When a robot begins navigation in an unknown area, it
      has no information about the surrounding environment. Accordingly, for robots to
      perform tasks based on location information, they need a simultaneous
      localization and mapping (SLAM) process that uses sensor information to draw a
      map of the environment, while simultaneously estimating the current location of
      the robot on the map. This paper aims to present a localization method based in
      cooperation between aerial and ground robots in an indoor environment. The
      proposed method allows a ground robot to reach accurate destination by using a
      2.5D elevation map built by a low-cost RGB-D (Red Green and Blue-Depth) sensor
      and 2D Laser sensor attached onto an aerial robot. A 2.5D elevation map is formed
      by projecting height information of an obstacle using depth information obtained
      by the RGB-D sensor onto a grid map, which is generated by using the 2D Laser
      sensor and scan matching. Experimental results demonstrate the effectiveness of
      the proposed method for its accuracy in location recognition and computing speed.

PMID- 29186845
TI  - Banning Asbestos in New Zealand, 1936-2016, an 80-Year Long Saga.
AB  - The banning by the New Zealand Government of the import and export of asbestos
      containing products resulted from the interplay of a number of factors. At a
      personal level, there were the actions of the asbestos sufferers, their families
      and support groups. At the political level, there were the activities of
      progressive trade union groups representing the hazardous trades, such as
      labourers, construction workers and demolition workers, and at a Government
      level, there was a positive response to these public health pressures. The
      Prohibition Order 2016 concerning Imports and Exports (asbestos-containing
      products) was the outcome of this 80-year long saga.

PMID- 29186842
TI  - cfa-miR-143 Promotes Apoptosis via the p53 Pathway in Canine Influenza Virus H3N2
      Infected Cells.
AB  - MicroRNAs regulate multiple aspects of the host response to viral infection. This
      study verified that the expression of cfa-miR-143 was upregulated in vivo and in
      vitro by canine influenza virus (CIV) H3N2 infection. To understand the role of
      cfa-miR-143 in CIV-infected cells, the target gene of cfa-miR-143 was identified
      and assessed for correlations with proteins involved in the apoptosis pathway. A
      dual luciferase reporter assay showed that cfa-miR-143 targets insulin-like
      growth factor binding protein 5 (Igfbp5). Furthermore, a miRNA agomir and
      antagomir of cfa-miR-143 caused the downregulation and upregulation of Igfbp5,
      respectively, in CIV-infected madin-darby canine kidney (MDCK) cells. This study
      demonstrated that cfa-miR-143 stimulated p53 and caspase3 activation and induced
      apoptosis via the p53 pathway in CIV H3N2-infected cells. In conclusion, CIV H3N2
      induced the upregulation of cfa-miR-143, which contributes to apoptosis via
      indirectly activating the p53-caspase3 pathway.

PMID- 29186844
TI  - Upconversion Luminescence Sensitized pH-Nanoprobes.
AB  - Photon upconversion materials, featuring excellent photophysical properties, are
      promising for bio-medical research due to their low autofluorescence, non
      cytotoxicity, low photobleaching and high photostability. Upconversion based pH
      nanoprobes are attracting considerable interest due to their superiority over pH
      sensitive molecular indicators and metal nanoparticles. Herein, we review the
      advances in upconversion based pH-nanoprobes, the first time in the seven years
      since their discovery in 2009. With a brief discussion on the upconversion
      materials and upconversion processes, the progress in this field has been
      overviewed, along with the toxicity and biodistribution of upconversion materials
      for intracellular application. We strongly believe that this survey will
      encourage the further pursuit of intense research for designing molecular pH
      sensors.

PMID- 29186846
TI  - Dimension Reduction Aided Hyperspectral Image Classification with a Small-sized
      Training Dataset: Experimental Comparisons.
AB  - Hyperspectral images (HSI) provide rich information which may not be captured by
      other sensing technologies and therefore gradually find a wide range of
      applications. However, they also generate a large amount of irrelevant or
      redundant data for a specific task. This causes a number of issues including
      significantly increased computation time, complexity and scale of prediction
      models mapping the data to semantics (e.g., classification), and the need of a
      large amount of labelled data for training. Particularly, it is generally
      difficult and expensive for experts to acquire sufficient training samples in
      many applications. This paper addresses these issues by exploring a number of
      classical dimension reduction algorithms in machine learning communities for HSI
      classification. To reduce the size of training dataset, feature selection (e.g.,
      mutual information, minimal redundancy maximal relevance) and feature extraction
      (e.g., Principal Component Analysis (PCA), Kernel PCA) are adopted to augment a
      baseline classification method, Support Vector Machine (SVM). The proposed
      algorithms are evaluated using a real HSI dataset. It is shown that PCA yields
      the most promising performance in reducing the number of features or spectral
      bands. It is observed that while significantly reducing the computational
      complexity, the proposed method can achieve better classification results over
      the classic SVM on a small training dataset, which makes it suitable for real
      time applications or when only limited training data are available. Furthermore,
      it can also achieve performances similar to the classic SVM on large datasets but
      with much less computing time.

PMID- 29186847
TI  - Economic Feasibility of Wireless Sensor Network-Based Service Provision in a
      Duopoly Setting with a Monopolist Operator.
AB  - We analyze the feasibility of providing Wireless Sensor Network-data-based
      services in an Internet of Things scenario from an economical point of view. The
      scenario has two competing service providers with their own private sensor
      networks, a network operator and final users. The scenario is analyzed as two
      games using game theory. In the first game, sensors decide to subscribe or not to
      the network operator to upload the collected sensing-data, based on a utility
      function related to the mean service time and the price charged by the operator.
      In the second game, users decide to subscribe or not to the sensor-data-based
      service of the service providers based on a Logit discrete choice model related
      to the quality of the data collected and the subscription price. The sinks and
      users subscription stages are analyzed using population games and discrete choice
      models, while network operator and service providers pricing stages are analyzed
      using optimization and Nash equilibrium concepts respectively. The model is shown
      feasible from an economic point of view for all the actors if there are enough
      interested final users and opens the possibility of developing more efficient
      models with different types of services.

PMID- 29186848
TI  - Adaptive Spatial Filter Based on Similarity Indices to Preserve the Neural
      Information on EEG Signals during On-Line Processing.
AB  - This work presents a new on-line adaptive filter, which is based on a similarity
      analysis between standard electrode locations, in order to reduce artifacts and
      common interferences throughout electroencephalography (EEG) signals, but
      preserving the useful information. Standard deviation and Concordance Correlation
      Coefficient (CCC) between target electrodes and its correspondent neighbor
      electrodes are analyzed on sliding windows to select those neighbors that are
      highly correlated. Afterwards, a model based on CCC is applied to provide higher
      values of weight to those correlated electrodes with lower similarity to the
      target electrode. The approach was applied to brain computer-interfaces (BCIs)
      based on Canonical Correlation Analysis (CCA) to recognize 40 targets of steady
      state visual evoked potential (SSVEP), providing an accuracy (ACC) of 86.44 +/-
      2.81%. In addition, also using this approach, features of low frequency were
      selected in the pre-processing stage of another BCI to recognize gait planning.
      In this case, the recognition was significantly ( p < 0.01 ) improved for most of
      the subjects ( A C C >= 74.79 % ) , when compared with other BCIs based on Common
      Spatial Pattern, Filter Bank-Common Spatial Pattern, and Riemannian Geometry.

PMID- 29186849
TI  - New Possibilities of Substance Identification Based on THz Time Domain
      Spectroscopy Using a Cascade Mechanism of High Energy Level Excitation.
AB  - Using an experiment with thin paper layers and computer simulation, we
      demonstrate the principal limitations of standard Time Domain Spectroscopy (TDS)
      based on using a broadband THz pulse for the detection and identification of a
      substance placed inside a disordered structure. We demonstrate the spectrum
      broadening of both transmitted and reflected pulses due to the cascade mechanism
      of the high energy level excitation considering, for example, a three-energy
      level medium. The pulse spectrum in the range of high frequencies remains
      undisturbed in the presence of a disordered structure. To avoid false absorption
      frequencies detection, we apply the spectral dynamics analysis method (SDA
      method) together with certain integral correlation criteria (ICC).

PMID- 29186850
TI  - Optimal Power Allocation Strategy in a Joint Bistatic Radar and Communication
      System Based on Low Probability of Intercept.
AB  - In this paper, we investigate a low probability of intercept (LPI)-based optimal
      power allocation strategy for a joint bistatic radar and communication system,
      which is composed of a dedicated transmitter, a radar receiver, and a
      communication receiver. The joint system is capable of fulfilling the
      requirements of both radar and communications simultaneously. First, assuming
      that the signal-to-noise ratio (SNR) corresponding to the target surveillance
      path is much weaker than that corresponding to the line of sight path at radar
      receiver, the analytically closed-form expression for the probability of false
      alarm is calculated, whereas the closed-form expression for the probability of
      detection is not analytically tractable and is approximated due to the fact that
      the received signals are not zero-mean Gaussian under target presence hypothesis.
      Then, an LPI-based optimal power allocation strategy is presented to minimize the
      total transmission power for information signal and radar waveform, which is
      constrained by a specified information rate for the communication receiver and
      the desired probabilities of detection and false alarm for the radar receiver.
      The well-known bisection search method is employed to solve the resulting
      constrained optimization problem. Finally, numerical simulations are provided to
      reveal the effects of several system parameters on the power allocation results.
      It is also demonstrated that the LPI performance of the joint bistatic radar and
      communication system can be markedly improved by utilizing the proposed scheme.

PMID- 29186851
TI  - GNSS/Electronic Compass/Road Segment Information Fusion for Vehicle-to-Vehicle
      Collision Avoidance Application.
AB  - The increasing number of vehicles in modern cities brings the problem of
      increasing crashes. One of the applications or services of Intelligent
      Transportation Systems (ITS) conceived to improve safety and reduce congestion is
      collision avoidance. This safety critical application requires sub-meter level
      vehicle state estimation accuracy with very high integrity, continuity and
      availability, to detect an impending collision and issue a warning or intervene
      in the case that the warning is not heeded. Because of the challenging city
      environment, to date there is no approved method capable of delivering this high
      level of performance in vehicle state estimation. In particular, the current
      Global Navigation Satellite System (GNSS) based collision avoidance systems have
      the major limitation that the real-time accuracy of dynamic state estimation
      deteriorates during abrupt acceleration and deceleration situations, compromising
      the integrity of collision avoidance. Therefore, to provide the Required
      Navigation Performance (RNP) for collision avoidance, this paper proposes a novel
      Particle Filter (PF) based model for the integration or fusion of real-time
      kinematic (RTK) GNSS position solutions with electronic compass and road segment
      data used in conjunction with an Autoregressive (AR) motion model. The real-time
      vehicle state estimates are used together with distance based collision avoidance
      algorithms to predict potential collisions. The algorithms are tested by
      simulation and in the field representing a low density urban environment. The
      results show that the proposed algorithm meets the horizontal positioning
      accuracy requirement for collision avoidance and is superior to positioning
      accuracy of GNSS only, traditional Constant Velocity (CV) and Constant
      Acceleration (CA) based motion models, with a significant improvement in the
      prediction accuracy of potential collision.

PMID- 29186852
TI  - Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD).
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally
      regulate the translation of messenger RNAs. Given the crucial role of miRNAs in
      gene expression, genetic variants within miRNA-related sequences may affect miRNA
      function and contribute to disease risk. Osteoporosis is characterized by reduced
      bone mass, and bone mineral density (BMD) is a major diagnostic proxy to assess
      osteoporosis risk. Here, we aimed to identify miRNAs that are involved in BMD
      using data from recent genome-wide association studies (GWAS) on femoral neck,
      lumbar spine and forearm BMD. Of 242 miRNA-variants available in the GWAS data,
      we found rs11614913:C > T in the precursor miR-196a-2 to be significantly
      associated with femoral neck-BMD (p-value = 9.9 * 10-7, beta = -0.038) and lumbar
      spine-BMD (p-value = 3.2 * 10-11, beta = -0.061). Furthermore, our sensitivity
      analyses using the Rotterdam study data showed a sex-specific association of
      rs11614913 with BMD only in women. Subsequently, we highlighted a number of miR
      196a-2 target genes, expressed in bone and associated with BMD, that may mediate
      the miRNA function in BMD. Collectively, our results suggest that miR-196a-2 may
      contribute to variations in BMD level. Further biological investigations will
      give more insights into the mechanisms by which miR-196a-2 control expression of
      BMD-related genes.

PMID- 29186853
TI  - Novel Magnetic Zinc Oxide Nanotubes for Phenol Adsorption: Mechanism Modeling.
AB  - Considering the great impact of a material's surface area on adsorption
      processes, hollow nanotube magnetic zinc oxide with a favorable surface area of
      78.39 m2/g was fabricated with the assistance of microwave technology in the
      presence of poly vinyl alcohol (PVA) as a stabilizing agent followed by sonic
      precipitation of magnetite nano-particles. Scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) micrographs identified the nanotubes'
      morphology in the synthesized material with an average aspect ratio of 3. X-ray
      diffraction (XRD) analysis verified the combination of magnetite material with
      the hexagonal wurtzite structure of ZnO in the prepared material. The
      immobilization of magnetite nanoparticles on to ZnO was confirmed using vibrating
      sample magnetometry (VSM). The sorption affinity of the synthesized magnetic ZnO
      nanotube for phenolic compounds from aqueous solutions was examined as a function
      of various processing factors. The degree of acidity of the phenolic solution has
      great influence on the phenol sorption process on to magnetic ZnO. The calculated
      value of DeltaH0 designated the endothermic nature of the phenol uptake process
      on to the magnetic ZnO nanotubes. Mathematical modeling indicated a combination
      of physical and chemical adsorption mechanisms of phenolic compounds on to the
      fabricated magnetic ZnO nanotubes. The kinetic process correlated better with the
      second-order rate model compared to the first-order rate model. This result
      indicates the predominance of the chemical adsorption process of phenol on to
      magnetic ZnO nanotubes.

PMID- 29186854
TI  - Evaluation of the Effects of Crushed and Expanded Waste Glass Aggregates on the
      Material Properties of Lightweight Concrete Using Image-Based Approaches.
AB  - Recently, the recycling of waste glass has become a worldwide issue in the
      reduction of waste and energy consumption. Waste glass can be utilized in
      construction materials, and understanding its effects on material properties is
      crucial in developing advanced materials. In this study, recycled crushed and
      expanded glasses are used as lightweight aggregates for concrete, and their
      relation to the material characteristics and properties is investigated using
      several approaches. Lightweight concrete specimens containing only crushed and
      expanded waste glass as fine aggregates are produced, and their pore and
      structural characteristics are examined using image-based methods, such as
      scanning electron microscopy (SEM), X-ray computed tomography (CT), and automated
      image analysis (RapidAir). The thermal properties of the materials are measured
      using both Hot Disk and ISOMET devices to enhance measurement accuracy.
      Mechanical properties are also evaluated, and the correlation between material
      characteristics and properties is evaluated. As a control group, a concrete
      specimen with natural fine sand is prepared, and its characteristics are compared
      with those of the specimens containing crushed and expanded waste glass
      aggregates. The obtained results support the usability of crushed and expanded
      waste glass aggregates as alternative lightweight aggregates.

PMID- 29186857
TI  - Techno-Economic Analysis of Biofuel Production from Macroalgae (Seaweed).
AB  - A techno-economic evaluation of bioenergy production from macroalgae was carried
      out in this study. Six different scenarios were examined for the production of
      different energy products and by-products. Seaweed was produced either via the
      longline method or the grid method. Final products of these scenarios were either
      ethanol from fermentation, or electricity from anaerobic digestion (AD). By
      products were digestate for AD, and animal feed, or electricity and digestate,
      for the fermentation pathway. Bioenergy breakeven selling prices were
      investigated according to the cost components and the feedstock supply chain,
      while suggestions for potential optimization of costs were provided. The lowest
      production level of dry seaweed to meet 0.93 ($/L) for ethanol fuel and 0.07 $/kW
      h for electricity was found to be 0.68 and 3.7 million tonnes (dry basis),
      respectively. At the moment, biofuel production from seaweed has been determined
      not to be economically feasible, but achieving economic production may be
      possible by lowering production costs and increasing the area under cultivation.

PMID- 29186855
TI  - Translational Aspects of Sphingolipid Metabolism in Renal Disorders.
AB  - Sphingolipids, long thought to be passive components of biological membranes with
      merely a structural role, have proved throughout the past decade to be major
      players in the pathogenesis of many human diseases. The study and
      characterization of several genetic disorders like Fabry's and Tay Sachs, where
      sphingolipid metabolism is disrupted, leading to a systemic array of clinical
      symptoms, have indeed helped elucidate and appreciate the importance of
      sphingolipids and their metabolites as active signaling molecules. In addition to
      being involved in dynamic cellular processes like apoptosis, senescence and
      differentiation, sphingolipids are implicated in critical physiological functions
      such as immune responses and pathophysiological conditions like inflammation and
      insulin resistance. Interestingly, the kidneys are among the most sensitive organ
      systems to sphingolipid alterations, rendering these molecules and the enzymes
      involved in their metabolism, promising therapeutic targets for numerous
      nephropathic complications that stand behind podocyte injury and renal failure.

PMID- 29186858
TI  - Differential Expression of Nitric Oxide Synthase Isoforms nNOS and iNOS in
      Patients with Non-Segmental Generalized Vitiligo.
AB  - Nitric oxide (NO) is involved in several biological processes, but its role in
      human melanogenesis is still not well understood. Exposure to UVA and UVB induces
      nitric oxide production in keratinocytes and melanocytes through the activation
      of constitutive nitric oxide synthase, increasing tyrosinase activity and melanin
      synthesis, whereas inducible nitric oxide synthase over expression might be
      involved in hypopigmentary disorders. The aim of this study was to evaluate
      whether inducible nitric oxide synthase and neuronal nitric oxide synthase
      expression were modified in vitiligo skin compared to healthy controls. Skin
      biopsies were obtained from inflammatory/lesional and white/lesional skin in 12
      patients with active, non-segmental vitiligo; site-matched biopsies of normal
      skin from eight patients were used as controls. Nitric oxide synthase isoforms
      expression was evaluated by confocal laser scanning microscopy and Western Blot
      analysis. Inducible nitric oxide synthase expression was significantly increased
      in inflammatory/lesional skin compared to healthy skin; melanocytes showed a
      moderate neuronal nitric oxide synthase expression in white/lesional skin,
      demonstrating that metabolic function still goes on. The obtained data
      demonstrated that vitiligo lesions were characterized by modifications of nitric
      oxide synthase isoforms, thus confirming the hypothesis that nitric oxide
      imbalance is involved in vitiligo and supporting the idea that nitric oxide
      synthase inhibitors might be used as a possible therapeutic approach for the
      management of vitiligo.

PMID- 29186859
TI  - Peanuts, Aflatoxins and Undernutrition in Children in Sub-Saharan Africa.
AB  - Peanuts (Arachis hypogaea) is an important and affordable source of protein in
      most of Sub-Saharan Africa (SSA) and a popular commodity and raw material for
      peanut butter, paste and cooking oil. It is a popular ingredient for foods used
      at the point of weaning infants from mother's milk. It is at this critical point
      that childhood undernutrition occurs and the condition manifests as stunting,
      wasting and growth restriction and accounts for nearly half of all deaths in
      children under five years of age in SSA. Undernutrition is multi-factorial but
      weaning foods contaminated with microbiological agents (bacteria and fungi) and
      natural toxins have been shown to play a big part. While peanuts may provide good
      nutrition, they are also highly prone to contamination with mycotoxigenic fungi.
      The high nutritive value of peanuts makes them a perfect substrate for fungal
      growth and potential aflatoxin contamination. Aflatoxins are highly carcinogenic
      and mutagenic mycotoxins. This article reviews the nutritional value and
      aflatoxin contamination of peanuts, the role they play in the development of
      childhood malnutrition (including the different theories of aetiology) and
      immunological problems in children. We also discuss the control strategies that
      have been explored and advocacy work currently taking shape in Africa to create
      more awareness of aflatoxins and thus combat their occurrence with the goal of
      reducing exposure and enhancing trade and food safety.

PMID- 29186860
TI  - BCL11A mRNA Targeting by miR-210: A Possible Network Regulating gamma-Globin Gene
      Expression.
AB  - The involvement of microRNAs in the control of repressors of human gamma-globin
      gene transcription has been firmly demonstrated, as described for the miR-486-3p
      mediated down-regulation of BCL11A. On the other hand, we have reported that miR
      210 is involved in erythroid differentiation and, possibly, in gamma-globin gene
      up-regulation. In the present study, we have identified the coding sequence of
      BCL11A as a possible target of miR-210. The following results sustain this
      hypothesis: (a) interactions between miR-210 and the miR-210 BCL11A site were
      demonstrated by SPR-based biomolecular interaction analysis (BIA); (b) the miR
      210 site of BCL11A is conserved through molecular evolution; (c) forced
      expression of miR-210 leads to decrease of BCL11A-XL and increase of gamma-globin
      mRNA content in erythroid cells, including erythroid precursors isolated from
      beta-thalassemia patients. Our study suggests that the coding mRNA sequence of
      BCL11A can be targeted by miR-210. In addition to the theoretical point of view,
      these data are of interest from the applied point of view, supporting a novel
      strategy to inhibit BCL11A by mimicking miR-210 functions, accordingly with the
      concept supported by several papers and patent applications that inhibition of
      BCL11A is an efficient strategy for fetal hemoglobin induction in the treatment
      of beta-thalassemia.

PMID- 29186861
TI  - Mental Health of the Prison Medical Workers (PMWs) and Influencing Factors in
      Jiangxi, China.
AB  - Prison medical workers (PMWs) are critically important, but they are also
      vulnerable to psychological problems. Currently, there is no study on examining
      PMWs' mental health conditions and possible influencing factors in China. Hence,
      we conducted this cross-sectional survey, aiming to understand the mental health
      status of the PMWs and related impact factors in Jiangxi province of China. We
      employed the Chinese version of the Symptom Checklist-90-R (SCL-90-R) to assess
      the mental disorders and psychological health conditions of PMWs in Jiangxi. The
      t tests were used to compare the differences for the average score of SCL-90-R
      between the Chinese general population and targeted PMWs of this study.
      Multivariable logistic regression analyses were conducted to identify the main
      factors associated with overall detection rate of PMWs' psychological health
      conditions. The scores of four dimensions (somatization, obsessive-compulsive
      symptoms, anxiety, and paranoid ideation) were significantly higher than the
      Chinese national norm, and the total positive rate was 49.09% among the PMWs.
      Gender, marital status, age, and length of employment are identified to be the
      most significant predictors to affect PMWs' mental health. Positive correlations
      between each of the nine dimensions of the SCL-90-R have been verified. This
      study demonstrated for the first time that PMWs are facing mental health risk and
      suffering serious psychological problems with psychopathology symptoms, which has
      become a growing concern in China. Our current findings suggest a need for more
      in-depth studies on this subject going forward to validate our conclusions and
      also to identify more impact factors, since such studies and knowledge of PMWs'
      mental health and influencing factors are very limited in China.

PMID- 29186856
TI  - Zinc as a Gatekeeper of Immune Function.
AB  - After the discovery of zinc deficiency in the 1960s, it soon became clear that
      zinc is essential for the function of the immune system. Zinc ions are involved
      in regulating intracellular signaling pathways in innate and adaptive immune
      cells. Zinc homeostasis is largely controlled via the expression and action of
      zinc "importers" (ZIP 1-14), zinc "exporters" (ZnT 1-10), and zinc-binding
      proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been
      documented, however, underlying mechanisms are still not entirely clear. Here, we
      report molecular mechanisms underlying the development of a pro-inflammatory
      phenotype during zinc deficiency. Furthermore, we describe links between altered
      zinc homeostasis and disease development. Consequently, the benefits of zinc
      supplementation for a malfunctioning immune system become clear. This article
      will focus on underlying mechanisms responsible for the regulation of cellular
      signaling by alterations in zinc homeostasis. Effects of fast zinc flux,
      intermediate "zinc waves", and late homeostatic zinc signals will be
      discriminated. Description of zinc homeostasis-related effects on the activation
      of key signaling molecules, as well as on epigenetic modifications, are included
      to emphasize the role of zinc as a gatekeeper of immune function.

PMID- 29186862
TI  - Study on the Anti-Poison Performance of Al-Y-P Master Alloy for Impurity Ca in
      Aluminum Alloys.
AB  - In this article, the anti-poison performance of novel Al-6Y-2P master alloy for
      impurity Ca in hypereutectic Al-Si alloys was investigated in detail. According
      to the microstructural analysis, it can be found that the primary Si and eutectic
      Si particles could be relatively modified and refined. In order to investigate
      the influence mechanism of Ca on the limited refinement performance of Al-6Y-2P
      master alloy, types of Al-xSi-2Ca-3Y-1P (x = 0, 6, 12, 18, and 30) alloys were
      prepared. It is observed that Ca takes the form of more stable Ca3P2 compounds by
      reacting with YP, and the surface of Ca3P2 particles are unsmooth, and even some
      have wrinkles in Al Al-2Ca-3Y-1P alloy. With the increase of Si content in Al-xSi
      2Ca-3Y-1P (x = 6, 12, 18 and 30) systems, the multi-encapsulation structures,
      i.e., the phosphide (AlP and YP), hexagonal Al2Si2Ca, the Al3Si2Y2 or primary Si
      from inside to outside in order were examined.The excapsulation of YP and AlP
      caused by Al2Si2Ca might be the reason for the limited refinement effect of Al-6Y
      2P master alloy for hypereutectic Al-18Si alloys.

PMID- 29186864
TI  - Brazilian Citizens: Expectations Regarding Dairy Cattle Welfare and Awareness of
      Contentious Practices.
AB  - The primary aim of this study was to explore attitudes of urban Brazilian
      citizens about dairy production. A secondary aim was to determine their knowledge
      and attitudes about four potentially contentious routine dairy cattle management
      practices: early cow-calf separation; zero-grazing; culling of newborn male
      calves; and dehorning without pain mitigation. To address the first aim 40
      participants were interviewed using open-ended semi-structured questions designed
      to probe their views and attitudes about dairy production in Brazil, and 300
      participants answered a questionnaire that included an open-ended question about
      the welfare of dairy cattle. Primary concerns reported by the participants
      centered on milk quality, which included the rejection of any chemical additives,
      but also animal welfare, environmental and social issues. The interviewees rarely
      mentioned animal welfare directly but, when probed, expressed several concerns
      related to this topic. In particular, participants commented on factors that they
      perceived to influence milk quality, such as good animal health, feeding, clean
      facilities, and the need to avoid or reduce the use of drugs, hormones and
      pesticides, the avoidance of pain, frustration and suffering, and the ability of
      the animals to perform natural behaviors. To address our second aim, participants
      were asked questions about the four routine management practices. Although they
      self-reported being largely unaware of these practices, the majority of the
      participants rejected these practices outright. These data provide insight that
      animal welfare may be an important issue for members of the public. Failure to
      consider this information may increase the risk that certain dairy production
      practices may not be socially sustainable once lay citizens become aware of them.

PMID- 29186863
TI  - Paraneoplastic Pemphigus: Insight into the Autoimmune Pathogenesis, Clinical
      Features and Therapy.
AB  - Paraneoplastic pemphigus is a rare autoimmune skin disease that is always
      associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the
      earliest manifestations shown by paraneoplastic pemphigus patients. The
      pathogenesis of paraneoplastic pemphigus is not yet completely understood,
      although some immunological aspects have been recently clarified. Because of its
      rarity, several diagnostic criteria have been proposed. Besides, several
      diagnostic procedures have been used for the diagnosis, including indirect
      immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most
      recent literature, searching on PubMed "paraneoplastic pemphigus". We included
      also papers in French, German, and Spanish. We found 613 papers for
      "paraneoplastic pemphigus". Among them, 169 were review papers. Because of its
      varying clinical features, paraneoplastic pemphigus still represents a challenge
      for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus
      requires close collaboration between physicians, including dermatologist,
      oncologist, and otorhinolaryngologist.

PMID- 29186865
TI  - Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic
      Conditions.
AB  - As current kidney replacement therapies are not efficient enough for end-stage
      renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on
      conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could
      represent an attractive solution. The active transport activity of such a system
      was recently demonstrated. In addition, endocrine functions of the cells, such as
      vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1)
      overexpressing ciPTEC line presented 1alpha-hydroxylase (CYP27B1), 24-hydroxylase
      (CYP24A1) and vitamin D receptor (VDR), responsible for vitamin D activation,
      degradation and function, respectively. The ability to produce and secrete
      1alpha,25-dihydroxy-vitamin D3, was shown after incubation with the precursor, 25
      hydroxy-vitamin D3. The beneficial effect of vitamin D on cell function and
      behavior in uremic conditions was studied in the presence of an anionic uremic
      toxins mixture. Vitamin D could restore cell viability, and inflammatory and
      oxidative status, as shown by cell metabolic activity, interleukin-6 (IL-6)
      levels and reactive oxygen species (ROS) production, respectively. Finally,
      vitamin D restored transepithelial barrier function, as evidenced by decreased
      inulin-FITC leakage in biofunctionalized hollow fiber membranes (HFM) carrying
      ciPTEC-OAT1. In conclusion, the protective effects of vitamin D in uremic
      conditions and proven ciPTEC-OAT1 endocrine function encourage the use of these
      cells for BAK application.

PMID- 29186867
TI  - Outlook on the Application of Metal-Liganded Bioactives for Stimuli-Responsive
      Release.
AB  - Direct metal-liganded bioactive coordination complexes are known to be sensitive
      to stimuli such as pH, light, ion activation, or redox cues. This results in the
      controlled release of the bioactive(s). Compared to other drug delivery
      strategies based on metal complexation, this type of coordination negates a multi
      step drug loading methodology and offers customized physiochemical properties
      through judicious choice of modulating ancillary ligands. Bioactive release
      depends on simple dissociative kinetics. Nonetheless, there are challenges
      encountered when translating the pure coordination chemistry into the biological
      and physiological landscape. The stability of the metal-bioactive complex in the
      biological milieu may be compromised, disrupting the stimuli-responsive release
      mechanism, with premature release of the bioactive. Research has therefore
      progressed to the incorporation of metal-liganded bioactives with established
      drug delivery strategies to overcome these limitations. This review will
      highlight and critically assess current research interventions in order to
      predict the direction that pharmaceutical scientists could pursue to arrive at
      tailored and effective metal-liganded bioactive carriers for stimuli-responsive
      drug release.

PMID- 29186866
TI  - TGF-beta1 in Vascular Wall Pathology: Unraveling Chronic Venous Insufficiency
      Pathophysiology.
AB  - Chronic venous insufficiency and varicose veins occur commonly in affluent
      countries and are a socioeconomic burden. However, there remains a relative lack
      of knowledge about venous pathophysiology. Various theories have been suggested,
      yet the molecular sequence of events is poorly understood. Transforming growth
      factor-beta one (TGF-beta1) is a highly complex polypeptide with multifunctional
      properties that has an active role during embryonic development, in adult organ
      physiology and in the pathophysiology of major diseases, including cancer and
      various autoimmune, fibrotic and cardiovascular diseases. Therefore, an emphasis
      on understanding its signaling pathways (and possible disruptions) will be an
      essential requirement for a better comprehension and management of specific
      diseases. This review aims at shedding more light on venous pathophysiology by
      describing the TGF-beta1 structure, function, activation and signaling, and
      providing an overview of how this growth factor and disturbances in its signaling
      pathway may contribute to specific pathological processes concerning the vessel
      wall which, in turn, may have a role in chronic venous insufficiency.

PMID- 29186868
TI  - Could -79  degrees C Spray-Type Cryotherapy Be an Effective Monotherapy for the
      Treatment of Keloid?
AB  - Cryotherapy has been regarded as an effective modality for the treatment of
      keloids, and the spray-type device is one of the novel cryotherapeutic units.
      However, the biological mechanisms and therapeutic effects of this technique are
      incompletely studied. We evaluated the clinical efficacy of our cryotherapy
      protocol with molecular and pathologic evidence for the treatment of keloids. We
      evenly split each of ten keloid lesions into a non-treated (C-) and treated (C+)
      area; the C+ area was subjected to two freeze-thaw cycles of spray-type
      cryotherapy using -79  degrees C spray-type CryoPenTM. This treatment was
      repeated after an interval of two weeks. The proliferation and migration
      abilities of the fibroblasts isolated from the dermis under the cryotherapy
      treated or untreated keloid tissues (at least 5 mm deep) were compared and
      pathologic findings of the full layer were evaluated. Molecular analysis revealed
      that the number of dermal fibroblasts was significantly higher in C+ group as
      compared with C- group. The dermal fibroblasts from C+ group showed more than two
      fold increase in the migration ability as compared with the fibroblasts from C-
      group. The expression of matrix metallopeptidase 9 was increased by more than two
      fold and a significant increase in transforming growth factor beta 1 expression
      and Smad2/3 phosphorylation level was observed in C+ group. C+ group showed more
      extensive lymphoplasmacytic infiltration with thicker fibrosis and occasional
      "proliferating core collagen" as compared with C- group. Thus, -79  degrees C
      spray-type cryotherapy is ineffective as a monotherapy and should be used in
      combination with intralesional corticosteroids or botulinum toxin A for
      favourable outcomes in the treatment of thick keloids.

PMID- 29186869
TI  - Screen-Printed Graphite Electrodes as Low-Cost Devices for Oxygen Gas Detection
      in Room-Temperature Ionic Liquids.
AB  - Screen-printed graphite electrodes (SPGEs) have been used for the first time as
      platforms to detect oxygen gas in room-temperature ionic liquids (RTILs). Up
      until now, carbon-based SPEs have shown inferior behaviour compared to platinum
      and gold SPEs for gas sensing with RTIL solvents. The electrochemical reduction
      of oxygen (O2) in a range of RTILs has therefore been explored on home-made
      SPGEs, and is compared to the behaviour on commercially-available carbon SPEs (C
      SPEs). Six common RTILs are initially employed for O2 detection using cyclic
      voltammetry (CV), and two RTILs ([C2mim][NTf2] and [C4mim][PF6]) chosen for
      further detailed analytical studies. Long-term chronoamperometry (LTCA) was also
      performed to test the ability of the sensor surface for real-time gas monitoring.
      Both CV and LTCA gave linear calibration graphs-for CV in the 10-100% vol. range,
      and for LTCA in the 0.1-20% vol. range-on the SPGE. The responses on the SPGE
      were far superior to the commercial C-SPEs; more instability in the
      electrochemical responses were observed on the C-SPEs, together with some
      breaking-up or dissolution of the electrode surface materials. This study
      highlights that not all screen-printed ink formulations are compatible with RTIL
      solvents for longer-term electrochemical experiments, and that the choice of RTIL
      is also important. Overall, the low-cost SPGEs appear to be promising platforms
      for the detection of O2, particularly in [C4mim][PF6].

PMID- 29186870
TI  - Dietary Supplementation with Lactobacillus casei Alleviates Lipopolysaccharide
      Induced Liver Injury in a Porcine Model.
AB  - This study aims to determine whether Lactobacillus casei (L. casei) could relieve
      liver injury in piglets challenged with lipopolysaccharide (LPS). Piglets were
      randomly allocated into one of the three groups: control, LPS, and L. casei. The
      control and LPS groups were fed a corn- and soybean meal-based diet, whereas the
      L. casei group was fed the basal diet supplemented with 6 * 106 cfu/g L. casei.
      On Day 31 of the trial, piglets in the LPS and L. casei groups received
      intraperitoneal administration of LPS (100 ug/kg body weight), while the control
      group received the same volume of saline. Blood and liver samples were collected
      for analysis. Results showed that L. casei supplementation decreased the
      feed/gain ratio (p = 0.027) and diarrhea incidence (p < 0.001), and attenuated
      LPS-induced liver histomorphological abnormalities. Compared with the control
      group, LPS challenge dramatically increased glutamyl transpeptidase activity (p =
      0.001) in plasma as well as the concentrations of Interleukin 6 (IL-6) (p =
      0.048), Tumor necrosis factor-alpha (TNF-alpha) (p = 0.041), and Malondialdehyde
      (MDA) (p = 0.001) in the liver, while decreasing the hepatic SOD activity. LPS
      also increased (p < 0.05) the mRNA levels for IL-6, IL-8, TNF-alpha, Toll-like
      receptors 4 (TLR4), Nuclear factor kappaB (NF-kappaB) and Heat shock protein 70
      (HSP70) in the liver. The adverse effects of LPS challenge were ameliorated by L.
      casei supplementation. In conclusion, dietary L. casei alleviates LPS-induced
      liver injury via reducing pro-inflammatory cytokines and increasing anti
      oxidative capacity.

PMID- 29186871
TI  - Plasmonic Optical Fiber-Grating Immunosensing: A Review.
AB  - Plasmonic immunosensors are usually made of a noble metal (in the form of a film
      or nanoparticles) on which bioreceptors are grafted to sense analytes based on
      the antibody/antigen or other affinity mechanism. Optical fiber configurations
      are a miniaturized counterpart to the bulky Kretschmann prism and allow easy
      light injection and remote operation. To excite a surface plasmon (SP), the core
      guided light is locally outcoupled. Unclad optical fibers were the first
      configurations reported to this end. Among the different architectures able to
      bring light in contact with the surrounding medium, a great quantity of research
      is today being conducted on metal-coated fiber gratings photo-imprinted in the
      fiber core, as they provide modal features that enable SP generation at any
      wavelength, especially in the telecommunication window. They are perfectly suited
      for use with cost-effective high-resolution interrogators, allowing both a high
      sensitivity and a low limit of detection to be reached in immunosensing. This
      paper will review recent progress made in this field with different kinds of
      gratings: uniform, tilted and eccentric short-period gratings as well as long
      period fiber gratings. Practical cases will be reported, showing that such
      sensors can be used in very small volumes of analytes and even possibly applied
      to in vivo diagnosis.

PMID- 29186872
TI  - Pre-Clinical Tests of an Integrated CMOS Biomolecular Sensor for Cardiac Diseases
      Diagnosis.
AB  - Coronary artery disease and its related complications pose great threats to human
      health. In this work, we aim to clinically evaluate a CMOS field-effect
      biomolecular sensor for cardiac biomarkers, cardiac-specific troponin-I (cTnI), N
      terminal prohormone brain natriuretic peptide (NT-proBNP), and interleukin-6 (IL
      6). The CMOS biosensor is implemented via a standard commercialized 0.35 MUm CMOS
      process. To validate the sensing characteristics, in buffer conditions, the
      developed CMOS biosensor has identified the detection limits of IL-6, cTnI, and
      NT-proBNP as being 45 pM, 32 pM, and 32 pM, respectively. In clinical serum
      conditions, furthermore, the developed CMOS biosensor performs a good correlation
      with an enzyme-linked immuno-sorbent assay (ELISA) obtained from a hospital
      central laboratory. Based on this work, the CMOS field-effect biosensor poses
      good potential for accomplishing the needs of a point-of-care testing (POCT)
      system for heart disease diagnosis.

PMID- 29186873
TI  - Thermoluminescence as a Research Tool to Investigate Luminescence Mechanisms.
AB  - Thermally stimulated luminescence (TSL) is known as a technique used in radiation
      dosimetry and dating. However, since the luminescence is very sensitive to the
      defects in a solid, it can also be used in material research. In this review, it
      is shown how TSL can be used as a research tool to investigate luminescent
      characteristics and underlying luminescent mechanisms. First, some basic
      characteristics and a theoretical background of the phenomenon are given. Next,
      methods and difficulties in extracting trapping parameters are addressed. Then,
      the instrumentation needed to measure the luminescence, both as a function of
      temperature and wavelength, is described. Finally, a series of very diverse
      examples is given to illustrate how TSL has been used in the determination of
      energy levels of defects, in the research of persistent luminescence phosphors,
      and in phenomena like band gap engineering, tunnelling, photosynthesis, and
      thermal quenching. It is concluded that in the field of luminescence
      spectroscopy, thermally stimulated luminescence has proven to be an experimental
      technique with unique properties to study defects in solids.

PMID- 29186874
TI  - Do Cervical Cancer Patients Diagnosed with Opportunistic Screening Live Longer?
      An Arkhangelsk Cancer Registry Study.
AB  - The aim of the current study was to compare cervical cancer (SS) patients
      diagnosed with and without screening in terms of: (i) sociodemographic and
      clinical characteristics; (ii) factors associated with survival; and (iii), and
      levels of risk. A registry-based study was conducted using data from the
      Arkhangelsk Cancer Registry. It included women with newly diagnosed malignant
      neoplasm of the uterine cervix during the period of 1 January 2005 to 11 November
      2016 (N = 1548). The Kaplan-Meier method, the log-rank test, and Cox regression
      were applied. Most participants who were diagnosed by screening were at stage I
      and died less frequently from CC than those diagnosed without screening. The
      latter group was also diagnosed with SS at a younger age and died younger.
      Younger individuals and urban residents diagnosed with stage I and II, squamous
      cell carcinoma had longer survival times. Cox regression modeling indicated that
      the hazard ratio for death among women with CC diagnosed without screening was
      1.61 (unadjusted) and 1.37 (adjusted). CC diagnosed by screening, cancer stage,
      patient residence, histological tumor type, and age at diagnosis were independent
      prognostic variables of longer survival time with CC. Diagnosis of CC made within
      a screening program improved survival.

PMID- 29186875
TI  - Distribution and Inferred Evolutionary Characteristics of a Chimeric ssDNA Virus
      Associated with Intertidal Marine Isopods.
AB  - Aquatic invertebrates are common reservoirs of a rapidly expanding group of
      circular Rep-encoding ssDNA (CRESS-DNA) viruses. This study identified and
      explored the phylogenetic relationship between novel CRESS-DNA viral genotypes
      associated with Pacific intertidal isopods Idotea wosnesenskii, Idotea resecata,
      and Gnorimosphaeroma oregonensis. One genotype associated with I. wosnesenskii,
      IWaV278, shared sequence similarity and genomic features with Tombusviridae
      (ssRNA) and Circoviridae (ssDNA) genomes and was putatively assigned to the
      Cruciviridae clade comprising chimeric viruses. The complete genome of IWaV278
      (3478 nt) was computationally completed, validated via Sanger sequencing, and
      exhibited sequence conservation and codon usage patterns analogous to other
      members of the Cruciviridae. Viral surveillance (qPCR) indicated that this virus
      was temporally transient (present in 2015, but not 2017), specific to I.
      wosnesenskii at a single collection site (Washington, DC, USA), more prevalent
      among male specimens, and frequently detected within exoskeletal structures. 18S
      rRNA sequences identified two alveolate protists associated with IWaV278-positive
      tissues and mechanical epibiont removal of ciliated exoskeletal structures
      eliminated viral detection, suggesting that the putative host of IWaV278 may be
      an epibiont of I. wosnesenskii. This investigation provides additional
      phylogenetic evidence to resolve Cruciviridae evolution and offers insight into
      the biogeography, specificity, and potential host of a crucivirus genotype.

PMID- 29186877
TI  - Insecticidal Effects of Plasma Treated Water.
AB  - The efficacy of plasma-treated tap water (PTW) for the possible treatment of a
      mealybug (Planococcus citri) infestation was studied under laboratory conditions.
      Mealybugs growing on Nerium oleander have been treated using PTW after being
      transferred to Petri dishes, thus avoiding possible buffering effects that might
      occur in an in-situ study. When treating tap water with a dielectric barrier
      discharge for several minutes (1, 3, 5 and 10 min) a distinct acidification of
      the water can be determined, resulting in a pH value of 1.8 after 10 min
      treatment. The efficacies of the treated tap water samples were compared to the
      efficacies achieved using classically acidified water. The classical
      acidification of tap water was carried out using nitric acid and hydrochloric
      acid to see any possible influences of the salt of the acid in question. The
      application of PTW revealed high mortality rates of approx. 90% after an
      observation period of 24 h. PTW appears promising for the treatment of smaller
      plant stock and commodities as produced by small scale farmers or in greenhouses
      as an environmentally friendly substitute or supplement to conventional
      pesticides.

PMID- 29186878
TI  - Dynamic Obstacle Avoidance for Unmanned Underwater Vehicles Based on an Improved
      Velocity Obstacle Method.
AB  - In view of a dynamic obstacle environment with motion uncertainty, we present a
      dynamic collision avoidance method based on the collision risk assessment and
      improved velocity obstacle method. First, through the fusion optimization of
      forward-looking sonar data, the redundancy of the data is reduced and the
      position, size and velocity information of the obstacles are obtained, which can
      provide an accurate decision-making basis for next-step collision avoidance.
      Second, according to minimum meeting time and the minimum distance between the
      obstacle and unmanned underwater vehicle (UUV), this paper establishes the
      collision risk assessment model, and screens key obstacles to avoid collision.
      Finally, the optimization objective function is established based on the improved
      velocity obstacle method, and a UUV motion characteristic is used to calculate
      the reachable velocity sets. The optimal collision speed of UUV is searched in
      velocity space. The corresponding heading and speed commands are calculated, and
      outputted to the motion control module. The above is the complete dynamic
      obstacle avoidance process. The simulation results show that the proposed method
      can obtain a better collision avoidance effect in the dynamic environment, and
      has good adaptability to the unknown dynamic environment.

PMID- 29186876
TI  - Melatonin Improves the Quality of Inferior Bovine Oocytes and Promoted Their
      Subsequent IVF Embryo Development: Mechanisms and Results.
AB  - The inferior oocytes (IOs), which are not suitable for embryo development, occupy
      roughly one-third or more of the collected immature bovine oocytes. The IOs are
      usually discarded from the in vitro bovine embryo production process. Improving
      the quality of the inferior oocytes (IOs) and make them available in in vitro
      embryo production would have important biological, as well as commercial, value.
      This study was designed to investigate whether melatonin could improve the
      quality of IOs and make them usable in the in vitro maturation (IVM) and
      subsequent (in vitro fertilization) IVF embryo development. The results indicated
      that: the maturation rate of IOs and their subsequent IVF embryo developments
      were impaired compared to cumulus-oocyte complexes and melatonin treatment
      significantly improved the quality of IOs, as well as their IVF and embryo
      developments. The potential mechanisms are that: (1) melatonin reduced reactive
      oxygen species (ROS) and enhanced glutathione (GSH) levels in the IOs, thereby
      protecting them from oxidative stress; (2) melatonin improved mitochondrial
      normal distribution and function to increase ATP level in IOs; and (3) melatonin
      upregulated the expression of ATPase 6, BMP-15, GDF-9, SOD-1, Gpx-4, and Bcl-2,
      which are critical genes for oocyte maturation and embryo development and
      downregulated apoptotic gene expression of caspase-3.

PMID- 29186880
TI  - Relation between the Disability of the Arm, Shoulder and Hand Score and Muscle
      Strength in Post-Cardiac Surgery Patients.
AB  - Background: The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire
      is a valid and reliable patient-reported outcome measure. DASH can be assessed by
      self-reported upper extremity disability and symptoms. We aimed to examine the
      relationship between the physiological outcome of muscle strength and the DASH
      score after cardiac surgery. Methods: This cross-sectional study assessed 50
      consecutive cardiac patients that were undergoing cardiac surgery. Physiological
      outcomes of handgrip strength and knee extensor muscle strength and the DASH
      score were measured at one month after cardiac surgery and were assessed. Results
      were analyzed using Spearman correlation coefficients. Results: The final
      analysis comprised 43 patients (men: 32, women: 11; age: 62.1 +/- 9.1 years; body
      mass index: 22.1 +/- 4.7 kg/m2; left ventricular ejection fraction: 53.5 +/-
      13.7%). Respective handgrip strength, knee extensor muscle strength, and DASH
      score were 27.4 +/- 8.3 kgf, 1.6 +/- 0.4 Nm/kg, and 13.3 +/- 12.3, respectively.
      The DASH score correlated negatively with handgrip strength (r = -0.38, p = 0.01)
      and with knee extensor muscle strength (r = -0.32, p = 0.04). Conclusion:
      Physiological outcomes of both handgrip strength and knee extensor muscle
      strength correlated negatively with the DASH score. The DASH score appears to be
      a valuable tool with which to assess cardiac patients with poor physiological
      outcomes, particularly handgrip strength as a measure of upper extremity
      function, which is probably easier to follow over time than lower extremity
      function after patients complete cardiac rehabilitation.

PMID- 29186881
TI  - A Novel Strategy for Quantitative Analysis of Major Ginsenosides in Panacis
      Japonici Rhizoma with a Standardized Reference Fraction.
AB  - Panacis Japonici Rhizoma (Zhu-Jie-Shen in Chinese), the root of P. japonicus C.A.
      Mey., is commonly used in traditional Chinese Medicine. Saponins are the major
      bioactive compounds in this herb. The similarity of polarity and structure of the
      natural products in herb caused the difficulty of purification and resulted in
      the shortage and high cost of the reference compounds, which has greatly hindered
      efforts toward quantification in quality control. A novel strategy using a
      standardized reference fraction for qualification of the major saponins in
      Panacis Japonici Rhizoma was proposed to easily and effectively control the
      quality of PJR. The strategy is feasible and reliable, and the methodology of the
      developed approach is also validated. The standardized reference fraction was
      used for quantification, which might solve the shortage of the pure reference
      compounds in the quality control of herbal medicines.

PMID- 29186879
TI  - The Weak Spots in Contemporary Science (and How to Fix Them).
AB  - In this review, the author discusses several of the weak spots in contemporary
      science, including scientific misconduct, the problems of post hoc hypothesizing
      (HARKing), outcome switching, theoretical bloopers in formulating research
      questions and hypotheses, selective reading of the literature, selective citing
      of previous results, improper blinding and other design failures, p-hacking or
      researchers' tendency to analyze data in many different ways to find positive
      (typically significant) results, errors and biases in the reporting of results,
      and publication bias. The author presents some empirical results highlighting
      problems that lower the trustworthiness of reported results in scientific
      literatures, including that of animal welfare studies. Some of the underlying
      causes of these biases are discussed based on the notion that researchers are
      only human and hence are not immune to confirmation bias, hindsight bias, and
      minor ethical transgressions. The author discusses solutions in the form of
      enhanced transparency, sharing of data and materials, (post-publication) peer
      review, pre-registration, registered reports, improved training, reporting
      guidelines, replication, dealing with publication bias, alternative inferential
      techniques, power, and other statistical tools.

PMID- 29186882
TI  - Finite Element Analysis of Tunable Composite Tubes Reinforced with Auxetic
      Structures.
AB  - A tubular composite structure that is built of two materials, characterized by
      different Young moduli, is analysed in this paper. The Young's modulus of one of
      these materials can be controlled by external conditions e.g., magnetic or
      electric field, temperature etc. The geometry of the reinforcement is based on
      typical auxetic re-entrant honeycomb cellular structure. The influence of this
      external factor on the behaviour of the stretched tube is analysed in this paper.
      Also, the possibility of creating a tubular composite structure whose cross
      section is either shrinking or expanding, while stretching the tube is presented.

PMID- 29186883
TI  - Consumers in a Sustainable Food Supply Chain (COSUS): Understanding Consumer
      Behavior to Encourage Food Waste Reduction.
AB  - Consumers are directly and indirectly responsible for a significant fraction of
      food waste which, for a large part, could be avoided if they were willing to
      accept food that is suboptimal, i.e., food that deviates in sensory
      characteristics (odd shape, discoloration), or that has a best-before date which
      is approaching or has passed, but that is still perfectly fine to eat. The choice
      to accept or discard suboptimal food is taken either before or after purchase
      (hence, in the retail store or in the household). The aim of the European
      research project COSUS (Consumers in a sustainable food supply chain) was to
      increase consumer acceptance of suboptimal food, before and after purchase, by
      implementing targeted strategies that are based on consumer insights, and that
      are feasible for and acceptable by the food sector. To reach this aim, different
      methodological approaches were applied to analyze this issue, to experiment with
      different aspects, and to test the resulting interventions. Each of these
      approaches was undertaken by competent consortium partners from Denmark, Germany,
      Norway, Sweden and The Netherlands. The project finally provides validated
      strategies to promote the distribution and consumption of suboptimal foods,
      thereby improving resource efficiency in the food chain and contributing to a
      more sustainable food supply.

PMID- 29186884
TI  - Cortisol Awakening Response, Internalizing Symptoms, and Life Satisfaction in
      Emerging Adults.
AB  - The cortisol awakening response (CAR) has been associated with depression and a
      broader range of internalizing problems. Emerging adulthood is characterized by
      numerous stressful transitional life events. Furthermore, the functioning of the
      neurobiological stress system changes across development. These considerations
      underscore the importance of evaluating the physiological stress system in
      emerging adults in identifying the extent to which cortisol levels vary with risk
      and protective factors for mental health. The present study evaluated the
      association between internalizing symptoms and perceived life satisfaction with
      CAR in 32 young adults. Three saliva samples were collected to measure cortisol
      levels upon awakening and participants completed the Depression Anxiety Stress
      Scale (DASS) and Satisfaction with Life Scale (SWLS). Results show a significant
      positive correlation between area under the curve for CAR with internalizing
      symptoms (DASS total) and the DASS-depression subscale, but not with life
      satisfaction. Study limitations, implications, and future directions for these
      finding were discussed.

PMID- 29186885
TI  - Plastic Deformation of Pressured Metallic Glass.
AB  - Although pressured metallic glass (MG) has been reported in the literature; there
      are few studies focusing on pressure effects on the structure; dynamics and its
      plastic deformation. In this paper; we report on and characterize; via molecular
      dynamics simulation, the structure and dynamics heterogeneity of pressured MGs,
      and explore a causal link between local structures and plastic deformation
      mechanism of pressured glass. The results exhibit that the dynamical
      heterogeneity of metallic liquid is more pronounced at high pressure, while the
      MGs were less fragile after the release of external pressure, reflected by the
      non-Gaussian parameter (NGP). High pressure glass shows better plastic
      deformation; and the local strain zone distributed more uniformly than of in
      normal glass. Further research indicates that although the number of icosahedrons
      in pressured glass was much larger than that in normal glass, while the
      interpenetrating connections of icosahedra (ICOI) exhibited spatial correlations
      were rather poor; In addition, the number of 'fast' atoms indexed by the atoms'
      moving distance is larger than that in normal glass; leading to the sharp
      decreasing in number of icosahedrons during deformation. An uniform distribution
      of 'fast' atoms also contributed to better plastic deformation ability in the
      pressured glass. These findings may suggest a link between the deformation and
      destruction of icosahedra with short-range order.

PMID- 29186888
TI  - Antioxidative Categorization of Twenty Amino Acids Based on Experimental
      Evaluation.
AB  - In view of the great importance bestowed on amino acids as antioxidants in
      oxidation resistance, we attempted two common redox titration methods in this
      report, including micro-potassium permanganate titration and iodometric
      titration, to measure the antioxidative capacity of 20 amino acids, which are the
      construction units of proteins in living organisms. Based on the relative
      intensities of the antioxidative capacity, we further conducted a quantitative
      comparison and found out that the product of experimental values obtained from
      the two methods was proven to be a better indicator for evaluating the relative
      antioxidative capacity of amino acids. The experimental results were largely in
      accordance with structural analysis made on amino acids. On the whole, the 20
      amino acids concerned could be divided into two categories according to their
      antioxidative capacity. Seven amino acids, including tryptophan, methionine,
      histidine, lysine, cysteine, arginine and tyrosine, were greater in total
      antioxidative capacity compared with the other 13 amino acids.

PMID- 29186887
TI  - IMU-Based Gait Recognition Using Convolutional Neural Networks and Multi-Sensor
      Fusion.
AB  - The wide spread usage of wearable sensors such as in smart watches has provided
      continuous access to valuable user generated data such as human motion that could
      be used to identify an individual based on his/her motion patterns such as, gait.
      Several methods have been suggested to extract various heuristic and high-level
      features from gait motion data to identify discriminative gait signatures and
      distinguish the target individual from others. However, the manual and hand
      crafted feature extraction is error prone and subjective. Furthermore, the motion
      data collected from inertial sensors have complex structure and the detachment
      between manual feature extraction module and the predictive learning models might
      limit the generalization capabilities. In this paper, we propose a novel approach
      for human gait identification using time-frequency (TF) expansion of human gait
      cycles in order to capture joint 2 dimensional (2D) spectral and temporal
      patterns of gait cycles. Then, we design a deep convolutional neural network
      (DCNN) learning to extract discriminative features from the 2D expanded gait
      cycles and jointly optimize the identification model and the spectro-temporal
      features in a discriminative fashion. We collect raw motion data from five
      inertial sensors placed at the chest, lower-back, right hand wrist, right knee,
      and right ankle of each human subject synchronously in order to investigate the
      impact of sensor location on the gait identification performance. We then present
      two methods for early (input level) and late (decision score level) multi-sensor
      fusion to improve the gait identification generalization performance. We
      specifically propose the minimum error score fusion (MESF) method that
      discriminatively learns the linear fusion weights of individual DCNN scores at
      the decision level by minimizing the error rate on the training data in an
      iterative manner. 10 subjects participated in this study and hence, the problem
      is a 10-class identification task. Based on our experimental results, 91% subject
      identification accuracy was achieved using the best individual IMU and 2DTF-DCNN.
      We then investigated our proposed early and late sensor fusion approaches, which
      improved the gait identification accuracy of the system to 93.36% and 97.06%,
      respectively.

PMID- 29186886
TI  - Protein Kinase Targets in Breast Cancer.
AB  - With 1.67 million new cases and 522,000 deaths in the year 2012, breast cancer is
      the most common type of diagnosed malignancy and the second leading cause of
      cancer death in women around the world. Despite the success of screening programs
      and the development of adjuvant therapies, a significant percentage of breast
      cancer patients will suffer a metastatic disease that, to this day, remains
      incurable and justifies the research of new therapies to improve their life
      expectancy. Among the new therapies that have been developed in recent years, the
      emergence of targeted therapies has been a milestone in the fight against cancer.
      Over the past decade, many studies have shown a causal role of protein kinase
      dysregulations or mutations in different human diseases, including cancer. Along
      these lines, cancer research has demonstrated a key role of many protein kinases
      during human tumorigenesis and cancer progression, turning these molecules into
      valid candidates for new targeted therapies. The subsequent discovery and
      introduction in 2001 of the kinase inhibitor imatinib, as a targeted treatment
      for chronic myelogenous leukemia, revolutionized cancer genetic pathways
      research, and lead to the development of multiple small-molecule kinase
      inhibitors against various malignancies, including breast cancer. In this review,
      we analyze studies published to date about novel small-molecule kinase inhibitors
      and evaluate if they would be useful to develop new treatment strategies for
      breast cancer patients.

PMID- 29186889
TI  - A Strategy for Identifying Quantitative Trait Genes Using Gene Expression
      Analysis and Causal Analysis.
AB  - Large numbers of quantitative trait loci (QTL) affecting complex diseases and
      other quantitative traits have been reported in humans and model animals.
      However, the genetic architecture of these traits remains elusive due to the
      difficulty in identifying causal quantitative trait genes (QTGs) for common QTL
      with relatively small phenotypic effects. A traditional strategy based on
      techniques such as positional cloning does not always enable identification of a
      single candidate gene for a QTL of interest because it is difficult to narrow
      down a target genomic interval of the QTL to a very small interval harboring only
      one gene. A combination of gene expression analysis and statistical causal
      analysis can greatly reduce the number of candidate genes. This integrated
      approach provides causal evidence that one of the candidate genes is a putative
      QTG for the QTL. Using this approach, I have recently succeeded in identifying a
      single putative QTG for resistance to obesity in mice. Here, I outline the
      integration approach and discuss its usefulness using my studies as an example.

PMID- 29186890
TI  - Investigation of Health Effects According to the Exposure of Low Concentration
      Arsenic Contaminated Ground Water.
AB  - Recent epidemiological studies have reported adverse health effects, including
      skin cancer, due to low concentrations of arsenic via drinking water. We
      conducted a study to assess whether low arsenic contaminated ground water
      affected health of the residents who consumed it. For precise biomonitoring
      results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As
      V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of
      arsenic were separately quantified by combining high-performance liquid
      chromatography and inductively coupled plasma mass spectroscopy from urine
      samples. In conclusion, urinary As III, As V, MMA, and hair arsenic
      concentrations were significantly higher in residents who consumed arsenic
      contaminated ground water than control participants who consumed tap water. But,
      most health screening results did not show a statistically significant difference
      between exposed and control subjects. We presume that the elevated arsenic
      concentrations may not be sufficient to cause detectable health effects.
      Consumption of arsenic contaminated ground water could result in elevated urinary
      organic and inorganic arsenic concentrations. We recommend immediate
      discontinuation of ground water supply in this area for the safety of the
      residents.

PMID- 29186891
TI  - Four Novel Zn (II) Coordination Polymers Based on 4'-Ferrocenyl-3,2':6',3''
      Terpyridine: Engineering a Switch from 1D Helical Polymer Chain to 2D Network by
      Coordination Anion Modulation.
AB  - Four novel ZnII coordination polymers, [(ZnCl2)2(L)2]n (1), [(ZnBr2)2(L)2]n (2),
      and [(ZnI2)2(L)2]n (3) and {[Zn(SCN)2]1.5(L)3}n (4), have been synthesized based
      on 4'-ferrocenyl-3,2':6',3''-terpyridine with ZnII ions and different
      coordination anions under similar ambient conditions. Their structures have been
      confirmed using single crystal X-ray diffraction analysis, showing that complexes
      1-3 are one-dimensional (1D) double-stranded metal ion helical polymer chains and
      complex 4 is of a two-dimensional (2D) network. The structural transformations of
      them from a 1D polymer chain to a 2D network under the influence of the
      coordination anions has been systematic investigated. Furthermore, the optical
      band gaps have been measured by optical diffuse reflectance spectroscopy,
      revealing that the ligand and the complexes should have semiconductor properties.

PMID- 29186892
TI  - Environmental Enrichment for Sucker and Weaner Pigs: The Effect of Enrichment
      Block Shape on the Behavioural Interaction by Pigs with the Blocks.
AB  - This experiment tested the effect of enrichment-block shape on oro-nasal contact
      by young pigs, and possible habituation to the blocks. Nineteen litters (197
      piglets) were randomly allocated to one of three block-shape treatments: Cube,
      Brick, or Wedge. Oro-nasal contact with blocks was infrequent before 25 days of
      age. Thereafter, contact steadily increased, suggesting enrichment blocks may not
      need to be provided until week 4 of lactation. Brick-shaped blocks attracted more
      oro-nasal contact than the cube and wedge shapes (p = 0.002). Oro-nasal contact
      was more frequent (p < 0.001) during the first 24 h after block introduction than
      when blocks were four days old. From 25 to 60 days of age, oro-nasal bouts were
      longer (p = 0.014) during the first 30 min of exposure to a fresh block, than for
      the remainder of the 24 h, or on day 4 after block replacement. Therefore,
      habituation to blocks may have occurred by 24 h after block introduction. Brick
      shaped blocks may present a wider surface for oro-nasal contact, where multiple
      pigs could simultaneously interact with the block. We speculate that simultaneous
      interaction with brick-shaped blocks may be similar to a litter co-operatively
      massaging the sow's udder prior to suckling bouts.

PMID- 29186894
TI  - One-Step Carbon Coating and Polyacrylamide Functionalization of Fe3O4
      Nanoparticles for Enhancing Magnetic Adsorptive-Remediation of Heavy Metals.
AB  - Magnetic nanoparticles are used in adsorptive removal of heavy metals from
      polluted wastewater. However, their poor stability in an acidic medium
      necessitates their protection with a coating layer. Coating magnetic
      nanoparticles with carbon showed proper protection but the heavy metal removal
      efficiency was slightly weak. However, to boost the removal efficiencies of
      surface functionalization, polyacrylamide was applied to carbon-coated Fe3O4
      nanoparticles. In this paper, to facilitate the synthesis process, one-step
      carbon coating and polyacrylamide functionalization were conducted using the
      hydrothermal technique with the aim of enhancing the adsorptive removal capacity
      of Fe3O4 nanoparticles towards some heavy metals such as Cu(II), Ni(II), Co(II),
      and Cd(II). The results showed that the one-step process succeeded in developing
      a carbon coating layer and polyacrylamide functionality on Fe3O4 nanoparticles.
      The stability of the magnetic Fe3O4 nanoparticles as an adsorbent in an acidic
      medium was improved due to its resistance to the dissolution that was gained
      during carbon coating and surface functionalization with polyacrylamide. The
      adsorptive removal process was investigated in relation to various parameters
      such as pH, time of contact, metal ion concentrations, adsorbent dose, and
      temperature. The polyacrylamide functionalized Fe3O4 showed an improvement in the
      adsorption capacity as compared with the unfunctionalized one. The conditions for
      superior adsorption were obtained at pH 6; time of contact, 90 min; metal
      solution concentration, 200 mg/L; adsorbent dose, 0.3 g/L. The modeling of the
      adsorption data was found to be consistent with the pseudo-second-order kinetic
      model, which suggests a fast adsorption process. However, the equilibrium data
      modeling was consistent with both the Langmuir and Freundlich isotherms.
      Furthermore, the thermodynamic parameters of the adsorptive removal process,
      including DeltaG degrees , DeltaH degrees , and DeltaS degrees , indicated a
      spontaneous and endothermic sorption process. The developed adsorbent can be
      utilized further for industrial-based applications.

PMID- 29186893
TI  - Effect of Salt Reduction on Consumer Acceptance and Sensory Quality of Food.
AB  - Reducing salt (NaCl) intake is an important public health target. The food
      industry and catering services are searching for means to reduce the salt content
      in their products. This review focuses on options for salt reduction in foods and
      the sensory evaluation of salt-reduced foods. Simple salt reduction, mineral
      salts and flavor enhancers/modifiers (e.g., umami compounds) are common options
      for salt reduction. In addition, the modification of food texture and odor-taste
      interactions may contribute to enhanced salty taste perception. Maintaining
      consumer acceptance of the products is a challenge, and recent examples of the
      consumer perception of salt-reduced foods are presented.

PMID- 29186895
TI  - Effects of Adding Clostridium sp. WJ06 on Intestinal Morphology and Microbial
      Diversity of Growing Pigs Fed with Natural Deoxynivalenol Contaminated Wheat.
AB  - Deoxynivalenol (DON) is commonly detected in cereals, and is a threat to human
      and animal health. The effects of microbiological detoxification are now being
      widely studied. A total of 24 pigs (over four months) were randomly divided into
      three treatments. Treatment A was fed with a basal diet as the control group.
      Treatment B was fed with naturally DON-contaminated wheat as a negative control
      group. Treatment C was fed with a contaminated diet that also had Clostridium sp.
      WJ06, which was used as a detoxicant. Growth performance, relative organ weight,
      intestinal morphology, and the intestinal flora of bacteria and fungi were
      examined. The results showed that after consuming a DON-contaminated diet, the
      growth performance of the pigs decreased significantly (p < 0.05), the relative
      organ weight of the liver and kidney increased significantly (p < 0.05), and the
      integrity of the intestinal barrier was also impaired, though the toxic effects
      of the contaminated diets on growing pigs were relieved after adding Clostridium
      sp. WJ06. The data from MiSeq sequencing of the 16S ribosomal ribonucleic acid
      (rRNA) gene and internal transcribed spacer 1 (ITS1) gene suggested that the
      abundance of intestinal flora was significantly different across the three
      treatments. In conclusion, the application of Clostridium sp. WJ06 can reduce the
      toxic effects of DON and adjust the intestinal microecosystem of growing pigs.

PMID- 29186896
TI  - The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial
      Processing.
AB  - The influence of genes and the environment on the development of Post-Traumatic
      Stress Disorder (PTSD) continues to motivate neuropsychological research, with
      one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene,
      given its impact on the integrity of the hippocampal memory system. Research into
      human navigation also considers the BDNF gene in relation to hippocampal
      dependent spatial processing. This speculative paper brings together trauma and
      spatial processing for the first time and presents exploratory research into
      their interactions with BDNF. We propose that quantifying the impact of BDNF on
      trauma and spatial processing is critical and may well explain individual
      differences in clinical trauma treatment outcomes and in navigation performance.
      Research has already shown that the BDNF gene influences PTSD severity and
      prevalence as well as navigation behaviour. However, more data are required to
      demonstrate the precise hippocampal dependent processing mechanisms behind these
      influences in different populations and environmental conditions. This paper
      provides insight from recent studies and calls for further research into the
      relationship between allocentric processing, trauma processing and BDNF. We argue
      that research into these neural mechanisms could transform PTSD clinical practice
      and professional support for individuals in trauma-exposing occupations such as
      emergency response, law enforcement and the military.

PMID- 29186897
TI  - Non-Coding RNAs in Pediatric Airway Diseases.
AB  - Non-coding RNAs (ncRNAs) are involved in the regulation of numerous biological
      processes and pathways and therefore have been extensively studied in human
      diseases. Previous reports have shown that non-coding RNAs play a crucial role in
      the pathogenesis and aberrant regulation of respiratory diseases. The altered
      expression of microRNAs (miRNAs) and long noncoding RNAs in blood and also
      locally in sputum or exhaled breath condensate influences lung function, immune
      response, and disease phenotype and may be used for the development of biomarkers
      specific for airway disease. In this review, we provide an overview of the recent
      works studying the non-coding RNAs in airway diseases, with a particular focus on
      chronic respiratory diseases of childhood. We have chosen the most common chronic
      respiratory condition-asthma- and the most severe, chronic disease of the airways
      cystic fibrosis. Study of the altered expression of non-coding RNAs in these
      diseases may be key to better understanding their pathogenesis and improving
      diagnosis, while also holding promise for the development of therapeutic
      strategies using the regulatory potential of non-coding RNAs.

PMID- 29186899
TI  - Obstacles to Brain Tumor Therapy: Key ABC Transporters.
AB  - The delivery of cancer chemotherapy to treat brain tumors remains a challenge, in
      part, because of the inherent biological barrier, the blood-brain barrier. While
      its presence and role as a protector of the normal brain parenchyma has been
      acknowledged for decades, it is only recently that the important transporter
      components, expressed in the tightly knit capillary endothelial cells, have been
      deciphered. These transporters are ATP-binding cassette (ABC) transporters and,
      so far, the major clinically important ones that functionally contribute to the
      blood-brain barrier are ABCG2 and ABCB1. A further limitation to cancer therapy
      of brain tumors or brain metastases is the blood-tumor barrier, where tumors
      erect a barrier of transporters that further impede drug entry. The expression
      and regulation of these two transporters at these barriers, as well as tumor
      derived alteration in expression and/or mutation, are likely obstacles to
      effective therapy.

PMID- 29186898
TI  - Thermodynamic Aspects and Reprogramming Cellular Energy Metabolism during the
      Fibrosis Process.
AB  - Fibrosis is characterized by fibroblast proliferation and fibroblast
      differentiation into myofibroblasts, which generate a relaxation-free contraction
      mechanism associated with excessive collagen synthesis in the extracellular
      matrix, which promotes irreversible tissue retraction evolving towards fibrosis.
      From a thermodynamic point of view, the mechanisms leading to fibrosis are
      irreversible processes that can occur through changing the entropy production
      rate. The thermodynamic behaviors of metabolic enzymes involved in fibrosis are
      modified by the dysregulation of both transforming growth factor beta (TGF-beta)
      signaling and the canonical WNT/beta-catenin pathway, leading to aerobic
      glycolysis, called the Warburg effect. Molecular signaling pathways leading to
      fibrosis are considered dissipative structures that exchange energy or matter
      with their environment far from the thermodynamic equilibrium. The
      myofibroblastic cells arise from exergonic processes by switching the core
      metabolism from oxidative phosphorylation to glycolysis, which generates energy
      and reprograms cellular energy metabolism to induce the process of myofibroblast
      differentiation. Circadian rhythms are far-from-equilibrium thermodynamic
      processes. They directly participate in regulating the TGF-beta and WNT/beta
      catenin pathways involved in energetic dysregulation and enabling fibrosis. The
      present review focusses on the thermodynamic implications of the reprogramming of
      cellular energy metabolism, leading to fibroblast differentiation into
      myofibroblasts through the positive interplay between TGF-beta and WNT/beta
      catenin pathways underlying in fibrosis.

PMID- 29186901
TI  - Live Fluorescent Staining Platform for Drug-Screening and Mechanism-Analysis in
      Zebrafish for Bone Mineralization.
AB  - Currently, drug screening relies on cell-based experiments or on animal models to
      confirm biological effects. The mammalian system is considered too time
      consuming, expensive and complex to perform high-throughput drug screening. There
      is a gap between in vitro cell-based models and the in vivo mammalian models. The
      zebrafish is an ideal model that could link preclinical toxicity screening with
      the drug development pipeline. Taking advantage of a highly conservative genomic,
      rapid development, large number of offspring, low cost and easy manipulation,
      zebrafish has been considered an excellent animal model for disease-based drug
      screening. In this study, zebrafish embryos were incubated with small molecular
      compounds that potentially affected bone mineralization in microplates. Two
      compounds of alendronate and dorsomorphin were used as positive and negative
      controls, respectively. The level of osteogenic mineralization was measured and
      quantified by using ImageJ software with fluorescent calcein-staining images.
      Among twenty-four tested compounds from the kinase inhibitor library, we
      identified two compounds, pentamidine and BML-267, which showed increased
      embryonic mineralization; while six compounds, RWJ-60475, levamisole HCL,
      tetramisole HCL, fenvalerate, NSC-663284, and BML-267ester, were inhibitory to
      bone mineralization. In addition, real time quantitative PCR (RT-qPCR) was
      performed to evaluate the biological pathways involved in bone metabolism at the
      molecular level. We confirmed that alendronate enhanced the level of bone
      mineralization by inhibiting osteoclast-related genes. In summary, our research
      established a simple method to screen potential bone metabolic drugs and to
      perform mechanism analysis for bone mineralization in vivo.

PMID- 29186902
TI  - Annotation of Peptide Structures Using SMILES and Other Chemical Codes-Practical
      Solutions.
AB  - Contemporary peptide science exploits methods and tools of bioinformatics, and
      cheminformatics. These approaches use different languages to describe peptide
      structures-amino acid sequences and chemical codes (especially SMILES),
      respectively. The latter may be applied, e.g., in comparative studies involving
      structures and properties of peptides and peptidomimetics. Progress in peptide
      science "in silico" may be achieved via better communication between biologists
      and chemists, involving the translation of peptide representation from amino acid
      sequence into SMILES code. Recent recommendations concerning good practice in
      chemical information include careful verification of data and their annotation.
      This publication discusses the generation of SMILES representations of peptides
      using existing software. Construction of peptide structures containing unnatural
      and modified amino acids (with special attention paid on glycosylated peptides)
      is also included. Special attention is paid to the detection and correction of
      typical errors occurring in SMILES representations of peptides and their
      correction using molecular editors. Brief recommendations for training of staff
      working on peptide annotations, are discussed as well.

PMID- 29186903
TI  - Bacteriological and Immunological Profiling of Meconium and Fecal Samples from
      Preterm Infants: A Two-Year Follow-Up Study.
AB  - An abnormal colonization pattern of the preterm gut may affect immune maturation
      and exert a long-term influence on the intestinal bacterial composition and host
      health. However, follow-up studies assessing the evolution of the fecal
      microbiota of infants that were born preterm are very scarce. In this work, the
      bacterial compositions of fecal samples, obtained from sixteen 2-year-old infants
      were evaluated using a phylogenetic microarray; subsequently, the results were
      compared with those obtained in a previous study from samples of meconium and
      feces collected from the same infants while they stayed in the neonatal intensive
      care unit (NICU). In parallel, the concentration of a wide range of cytokines,
      chemokines, growth factors and immunoglobulins were determined in meconium and
      fecal samples. Globally, a higher bacterial diversity and a lower interindividual
      variability were observed in 2-year-olds' feces, when compared to the samples
      obtained during their first days of life. Hospital-associated fecal bacteria,
      that were dominant during the NICU stay, seemed to be replaced, two years later,
      by genera, which are usually predominant in the healthy adult microbiome. The
      immune profile of the meconium and fecal samples differed, depending on the
      sampling time, showing different immune maturation statuses of the gut.

PMID- 29186900
TI  - Rodent Papillomaviruses.
AB  - Preclinical infection model systems are extremely valuable tools to aid in our
      understanding of Human Papillomavirus (HPV) biology, disease progression,
      prevention, and treatments. In this context, rodent papillomaviruses and their
      respective infection models are useful tools but remain underutilized resources
      in the field of papillomavirus biology. Two rodent papillomaviruses, MnPV1, which
      infects the Mastomys species of multimammate rats, and MmuPV1, which infects
      laboratory mice, are currently the most studied rodent PVs. Both of these viruses
      cause malignancy in the skin and can provide attractive infection models to study
      the lesser understood cutaneous papillomaviruses that have been frequently
      associated with HPV-related skin cancers. Of these, MmuPV1 is the first reported
      rodent papillomavirus that can naturally infect the laboratory strain of mice.
      MmuPV1 is an attractive model virus to study papillomavirus pathogenesis because
      of the ubiquitous availability of lab mice and the fact that this mouse species
      is genetically modifiable. In this review, we have summarized the knowledge we
      have gained about PV biology from the study of rodent papillomaviruses and point
      out the remaining gaps that can provide new research opportunities.

PMID- 29186904
TI  - The Roles of microRNAs in Regulating the Expression of PD-1/PD-L1 Immune
      Checkpoint.
AB  - Engagement of programmed death-ligand 1 (PD-L1) with its receptor programmed
      death 1 (PD-1) on T cells has been speculated to play a major role in suppressing
      the immune system, which helps tumor cells evade anti-tumor immunity. With the
      development of whole genome sequencing technologies, microRNAs have gained more
      attention as an important new layer of molecular regulation. Recent studies have
      revealed that altered expression of microRNAs play a pivotal role in immune
      checkpoint and various cellular processes in cancer. In this review, we focused
      on the latest progress about microRNAs research which involves the regulation of
      PD-1/PD-L1 immune checkpoint.

PMID- 29186905
TI  - Development of Cell-Specific Aptamers: Recent Advances and Insight into the
      Selection Procedures.
AB  - Systematic evolution of ligands by exponential enrichment (SELEX) is an
      established procedure for developing short single-stranded nucleic acid ligands
      called aptamers against a target of choice. This approach has also been used for
      developing aptamers specific to whole cells named Cell-SELEX. Aptamers selected
      by Cell-SELEX have the potential to act as cell specific therapeutics, cell
      specific markers or cell specific drug delivery and imaging agents. However,
      aptamer development is a laborious and time-consuming process which is often
      challenging due to the requirement of frequent optimization of various steps
      involved in Cell-SELEX procedures. This review provides an insight into various
      procedures for selection, aptamer enrichment, regeneration and aptamer-binding
      analysis, in addition to a very recent update on all aptamers selected by Cell
      SELEX procedures.

PMID- 29186906
TI  - Design, Synthesis and Bioactivities of Novel Isoxazole-Containing Pyrazole Oxime
      Derivatives.
AB  - In this study, in order to find novel biologically active pyrazole oxime
      derivatives, twenty-eight new pyrazole oxime compounds containing a substituted
      isoxazole ring were synthesized and evaluated for their acaricidaland
      insecticidal activities. Bioassays exhibited that some target compounds indicated
      good acaricidal and insecticidal activities against Tetranychus cinnabarinus,
      Aphis medicaginis, Mythimna separata, and Nilaparvata lugens. Especially,
      compounds 9c, 9h, 9u, and 9v showed 100.00%, 90.56%, 90.78%, and 90.62%
      insecticidal activities against A. medicaginis at the concentration of 20 MUg/mL,
      respectively, compounds 9k and 9u had 70.86% and 100.00% insecticidal activities
      against M. separata at 20 MUg/mL, respectively.

PMID- 29186907
TI  - Effect of Clinically Relevant CAD/CAM Zirconia Polishing on Gingival Fibroblast
      Proliferation and Focal Adhesions.
AB  - Mucosal seal formation around dental abutments is critical to the successful
      integration of dental implants into the human oral cavity. No information exists
      for how clinically relevant polishing procedures for computer-aided design and
      computer-aided manufactured (CAD/CAM) zirconia abutments affects cellular
      responses important to mucosal seal formation. CAD/CAM zirconia was divided into
      four groups for clinically relevant polishing utilizing commercial polishing
      heads: control, coarse, coarse plus medium, and coarse plus medium plus fine.
      Surfaces were analyzed with scanning electron microscopy (SEM), atomic force
      microscopy (AFM), and optical profilometry (OP). Subsequently, human gingival
      fibroblasts (HGFs) were seeded onto the zirconia surfaces. Proliferation was
      measured via a quantitative SEM technique and focal adhesion kinase (FAK)
      phosphorylation status was measured by an enzyme-linked immunosorbent assay
      (ELISA). Results showed an increase in proliferation on all polished surfaces as
      compared to the control. Phosphorylation of FAK at tyrosine 397 (Y397) was up
      modulated on the control surfaces. The associated cell adaptation is discussed.
      In all cases, FAK phosphorylation was greater at 24 h than 48 h. These results
      suggest that clinicians should be mindful of the effects of abutment polishing
      methodology, as this may have an impact on early mucosal seal formation.

PMID- 29186908
TI  - The Effect of a Diet Moderately High in Protein and Fiber on Insulin Sensitivity
      Measured Using the Dynamic Insulin Sensitivity and Secretion Test (DISST).
AB  - Evidence shows that weight loss improves insulin sensitivity but few studies have
      examined the effect of macronutrient composition independently of weight loss on
      direct measures of insulin sensitivity. We randomised 89 overweight or obese
      women to either a standard diet (StdD), that was intended to be low in fat and
      relatively high in carbohydrate (n = 42) or to a relatively high protein (up to
      30% of energy), relatively high fibre (>30 g/day) diet (HPHFib) (n = 47) for 10
      weeks. Advice regarding strict adherence to energy intake goals was not given.
      Insulin sensitivity and secretion was assessed by a novel method-the Dynamic
      Insulin Sensitivity and Secretion Test (DISST). Although there were significant
      improvements in body composition and most cardiometabolic risk factors on HPHFib,
      insulin sensitivity was reduced by 19.3% (95% CI: 31.8%, 4.5%; p = 0.013) in
      comparison with StdD. We conclude that the reduction in insulin sensitivity after
      a diet relatively high in both protein and fibre, despite cardiometabolic
      improvements, suggests insulin sensitivity may reflect metabolic adaptations to
      dietary composition for maintenance of glucose homeostasis, rather than impaired
      metabolism.

PMID- 29186910
TI  - Mn-Doped CaBi4Ti4O15/Pb(Zr,Ti)O3 Ultrasonic Transducers for Continuous Monitoring
      at Elevated Temperatures.
AB  - Continuous ultrasonic in-situ monitoring for industrial applications is difficult
      owing to the high operating temperatures in industrial fields. It is expected
      that ultrasonic transducers consisting of a CaBi4Ti4O15(CBT)/Pb(Zr,Ti)O3(PZT) sol
      gel composite could be one solution for ultrasonic nondestructive testing (NDT)
      above 500  degrees C because no couplant is required and CBT has a high Curie
      temperature. To verify the high temperature durability, CBT/PZT sol-gel composite
      films were fabricated on titanium substrates by spray coating, and the CBT/PZT
      samples were tested in a furnace at various temperatures. Reflected echoes with a
      high signal-to-noise ratio were observed up to 600  degrees C. A thermal cycle
      test was conducted from room temperature to 600  degrees C, and no significant
      deterioration was found after the second thermal cycle. To investigate the long
      term high-temperature durability, a CBT/PZT ultrasonic transducer was tested in
      the furnace at 600  degrees C for 36 h. Ultrasonic responses were recorded every
      3 h, and the sensitivity and signal-to-noise ratio were stable throughout the
      experiment.

PMID- 29186909
TI  - Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell
      Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition.
AB  - Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to
      major pathological processes involved in the development of cardiovascular
      diseases. The use of anti-proliferative agents for VSMCs offers potential for the
      treatment of vascular disorders. Intravenous anesthetics are firmly established
      to have direct effects on VSMCs, resulting in modulation of blood pressure.
      Ketamine has been used for many years in the intensive care unit (ICU) for
      sedation, and has recently been considered for adjunctive therapy. In the present
      study, we investigated the effects of ketamine on platelet-derived growth factor
      BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine
      concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without
      cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal
      regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively,
      have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and
      ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein
      phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB
      induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse
      2a (pp2a) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl
      sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly
      reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited
      tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent
      manner. In addition, the pp2a siRNA potently reversed the ketamine-activated
      catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti
      proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks
      PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation
      of VSMCs. Thus, ketamine may be considered a potential effective therapeutic
      agent for reducing atherosclerotic process by blocking the proliferation of
      VSMCs.

PMID- 29186911
TI  - Prostaglandin E2 in the Regulation of Water Transport in Renal Collecting Ducts.
AB  - The kidney plays a central role in the regulation of the body water balance. The
      process of targeting the water channel aquaporin-2 (AQP2) on the apical plasma
      membrane of the collecting duct (CD) principal cells is mainly regulated by the
      antidiuretic peptide hormone arginine vasopressin (AVP), which is responsible for
      the maintenance of water homeostasis. Recently, much attention has been focused
      on the local factors modulating renal water reabsorption by AQP2 in the
      collecting ducts, especially prostaglandin E2 (PGE2). PGE2 is a lipid mediator
      involved in a variety of physiological and pathophysiological processes in the
      kidney. The biological function of PGE2 is mainly mediated by four G-protein
      coupled receptors, namely EP1-4, which couple to drive separate intracellular
      signaling pathways. Increasing evidence demonstrates that PGE2 is essential for
      renal water transport regulation via multiple mechanisms. Each EP receptor plays
      a unique role in regulating water reabsorption in renal collecting ducts. This
      brief review highlights the role of PGE2 in the regulation of water reabsorption
      and discusses the involvement of each EP receptor subtype in renal collecting
      duct. A better understanding of the role of PGE2 in renal water transport process
      may improve disease management strategies for water balance disorders, including
      nephrogenic diabetes insipidus.

PMID- 29186913
TI  - Colorectal Cancer and Colitis Diagnosis Using Fourier Transform Infrared
      Spectroscopy and an Improved K-Nearest-Neighbour Classifier.
AB  - Combining Fourier transform infrared spectroscopy (FTIR) with endoscopy, it is
      expected that noninvasive, rapid detection of colorectal cancer can be performed
      in vivo in the future. In this study, Fourier transform infrared spectra were
      collected from 88 endoscopic biopsy colorectal tissue samples (41 colitis and 47
      cancers). A new method, viz., entropy weight local-hyperplane k-nearest-neighbor
      (EWHK), which is an improved version of K-local hyperplane distance nearest
      neighbor (HKNN), is proposed for tissue classification. In order to avoid
      limiting high dimensions and small values of the nearest neighbor, the new EWHK
      method calculates feature weights based on information entropy. The average
      results of the random classification showed that the EWHK classifier for
      differentiating cancer from colitis samples produced a sensitivity of 81.38% and
      a specificity of 92.69%.

PMID- 29186912
TI  - Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as
      Alzheimer's Disease Therapeutic Agents.
AB  - Computer-aided drug discovery/design (CADD) techniques allow the identification
      of natural products that are capable of modulating protein functions in
      pathogenesis-related pathways, constituting one of the most promising lines
      followed in drug discovery. In this paper, we computationally evaluated and
      reported the inhibitory activity found in meridianins A-G, a group of marine
      indole alkaloids isolated from the marine tunicate Aplidium, against various
      protein kinases involved in Alzheimer's disease (AD), a neurodegenerative
      pathology characterized by the presence of neurofibrillary tangles (NFT). Balance
      splitting between tau kinase and phosphate activities caused tau
      hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition
      of specific kinases involved in its phosphorylation pathway could be one of the
      key strategies to reverse tau hyperphosphorylation and would represent an
      approach to develop drugs to palliate AD symptoms. Meridianins bind to the
      adenosine triphosphate (ATP) binding site of certain protein kinases, acting as
      ATP competitive inhibitors. These compounds show very promising scaffolds to
      design new drugs against AD, which could act over tau protein kinases Glycogen
      synthetase kinase-3 Beta (GSK3beta) and Casein kinase 1 delta (CK1delta, CK1D or
      KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation
      regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to
      highlight the role of CADD techniques in marine drug discovery and to provide
      precise information regarding the binding mode and strength of meridianins
      against several protein kinases that could help in the future development of anti
      AD drugs.

PMID- 29186914
TI  - The Contribution of New Areas to the Total Hirsutism Scores in Basrah Hirsute
      Women.
AB  - BACKGROUND: Hirsutism is the presence of excessive growth of terminal hair in a
      female in the male-like pattern. It is the most common indicator of
      hyperandrogenism. The primary objective of this study was to evaluate the
      clinical impact of new androgens sensitive skin area to total body hirsutism
      score. METHODS: This was cross-sectional study. Most of the patients in this
      study group (n = 300) were women of reproductive age group (20-39 years) with a
      mean age of 26.6 +/- 7.1 years. They were recruited in Faiha Specialized
      Diabetes, Endocrine, and Metabolism Center (FDEMC) during the period from August
      2016 to the end of August 2017. All complained from hirsutism and were assessed
      by using modified Ferriman-Gallwey (m-FG) score system by a single examiner. Each
      patient underwent detailed clinical assessment in addition to transabdominal or
      transvaginal ultrasonography of the pelvis with endocrinological investigations.
      RESULTS: Comparison of the mean score at different body areas revealed that new
      androgens sensitive skin areas (sideburn, lower jaw/neck, buttocks/perineum) were
      comparable to others area of original m-FG score system or higher than at least
      three area used in the score. The sideburn area was observed to have the highest
      score among the new androgens sensitive skin areas. CONCLUSION: Evaluating the
      terminal hair growth in the new three androgen-sensitive skin areas (sideburn,
      lower jaw/neck, and buttocks/perineum) were clinically useful in assessing
      hirsutism score with high impact on total score.

PMID- 29186915
TI  - Development of a Dog-Assisted Activity Program in an Elementary Classroom.
AB  - Here we describe a pilot Dog-Assisted Activity program that was designed to
      improve wellbeing and social integration in a multi-cultural elementary classroom
      in which some episodes of bullying had been reported. We developed a 5-encounters
      protocol with the aim of introducing pet dogs into the class to stimulate
      understanding of different types of communication and behavior, ultimately
      facilitating positive relationships among peers. A preliminary evaluation was
      carried out in order to assess the effect of the program on teachers' perception
      of children's difficulties (e.g., peer relationship problems) and strengths
      (prosocial behaviors) by means of a brief behavioral screening tool, the
      Strengths and Difficulties Questionnaire (SDQ-Teacher version). Overall results
      indicate that, by means of the recognition of the dogs' behavior and non-verbal
      communication, children were able to express their emotions and to show behaviors
      that had not been recognized by the teachers prior to the intervention. In
      particular, the SDQ Total Difficulties scores suggest that the teacher had
      increased awareness of the students' difficulties as a result of the dog-assisted
      program. Overall, the presence of animals in the educational environment may
      provide enjoyment and hands-on educational experiences, enhanced psychological
      wellbeing, and increased empathy and socio-emotional development.

PMID- 29186917
TI  - The Design and Evaluation of an l-Dopa-Lazabemide Prodrug for the Treatment of
      Parkinson's Disease.
AB  - l-Dopa, the metabolic precursor of dopamine, is the treatment of choice for the
      symptomatic relief of the advanced stages of Parkinson's disease. The oral
      bioavailability of l-dopa, however, is only about 10% to 30%, and less than 1% of
      the oral dose is estimated to reach the brain unchanged. l-Dopa's physicochemical
      properties are responsible for its poor bioavailability, short half-life and the
      wide range of inter- and intrapatient variations of plasma levels. An l-dopa
      lazabemide prodrug is proposed to overcome the problems associated with l-dopa
      absorption. Lazabemide is a monoamine oxidase (MAO)-B inhibitor, a class of
      compounds that slows the depletion of dopamine stores in Parkinson's disease and
      elevates dopamine levels produced by exogenously administered l-dopa. l-Dopa was
      linked at the carboxylate with the primary aminyl functional group of lazabemide
      via an amide, a strategy which is anticipated to protect l-dopa against
      peripheral decarboxylation and possibly also enhance the membrane permeability of
      the prodrug. Selected physicochemical and biochemical properties of the prodrug
      were determined and included lipophilicity (logD), solubility, passive diffusion
      permeability, pKa, chemical and metabolic stability as well as cytotoxicity.
      Although oral and i.p. treatment of mice with the prodrug did not result in
      enhanced striatal dopamine levels, 3,4-dihydroxyphenylacetic acid (DOPAC) levels
      were significantly depressed compared to saline, l-dopa and carbidopa/l-dopa
      treatment. Based on the results, further preclinical evaluation of the l-dopa
      lazabemide prodrug should be undertaken with the aim of discovering prodrugs that
      may be advanced to the clinical stages of development.

PMID- 29186916
TI  - Ecology and Evolution in the RNA World Dynamics and Stability of Prebiotic
      Replicator Systems.
AB  - As of today, the most credible scientific paradigm pertaining to the origin of
      life on Earth is undoubtedly the RNA World scenario. It is built on the
      assumption that catalytically active replicators (most probably RNA-like
      macromolecules) may have been responsible for booting up life almost four billion
      years ago. The many different incarnations of nucleotide sequence (string)
      replicator models proposed recently are all attempts to explain on this basis how
      the genetic information transfer and the functional diversity of prebiotic
      replicator systems may have emerged, persisted and evolved into the first living
      cell. We have postulated three necessary conditions for an RNA World model system
      to be a dynamically feasible representation of prebiotic chemical evolution: (1)
      it must maintain and transfer a sufficient diversity of information reliably and
      indefinitely, (2) it must be ecologically stable and (3) it must be
      evolutionarily stable. In this review, we discuss the best-known prebiotic
      scenarios and the corresponding models of string-replicator dynamics and assess
      them against these criteria. We suggest that the most popular of prebiotic
      replicator systems, the hypercycle, is probably the worst performer in almost all
      of these respects, whereas a few other model concepts (parabolic replicator, open
      chaotic flows, stochastic corrector, metabolically coupled replicator system) are
      promising candidates for development into coherent models that may become
      experimentally accessible in the future.

PMID- 29186918
TI  - Depressive Symptom and Related Factors: A Cross-Sectional Study of Korean Female
      Workers Working at Traditional Markets.
AB  - BACKGROUND: Depression is one of the psychiatric diseases with a high prevalence
      rate, globally, and reportedly more prevalent among women than among men.
      Especially, women workers working at traditional markets are in depressive
      conditions without occupational health services. The purpose of this study is to
      investigate factors having a significant effect on the depressive symptoms of
      women workers at traditional markets in South Korea. METHODS: A cross-sectional
      study was used and subjects for the present study were 500 female workers in
      three selected representative traditional marketplaces in South Korea. RESULTS:
      The results of hierarchical regression analysis indicated that increased BMI
      (beta = 0.297, p = 0.017), poor nutritional status (beta = 0.596, p < 0.001),
      street vendor status (beta = 2.589, p = 0.001), job stress (beta = 0.491, p <
      0.001), lower back pain (beta = 0.377, p = 0.011), lower self-efficacy (beta = 
      0.368, p = 0.002) and diminished family function (beta = -0.633, p = 0.001)
      affected workers' depressive symptoms. The explanatory power of these variables
      was 38.5%. CONCLUSIONS: Based on these results, future research should focus on
      incorporating theses significant factors into effective interventions designed to
      decrease depressive symptoms in this population. Moreover, this study will
      increase interest in occupational health nursing, particularly in relation to
      vulnerable social groups, and expand the scope of practice in the field.

PMID- 29186919
TI  - A Strategic Bargaining Game for a Spectrum Sharing Scheme in Cognitive Radio
      Based Heterogeneous Wireless Sensor Networks.
AB  - In Wireless Sensor Networks (WSNs), unlicensed users, that is, sensor nodes, have
      excessively exploited the unlicensed radio spectrum. Through Cognitive Radio
      (CR), licensed radio spectra, which are owned by licensed users, can be partly or
      entirely shared with unlicensed users. This paper proposes a strategic bargaining
      spectrum-sharing scheme, considering a CR-based heterogeneous WSN (HWSN). The
      sensors of HWSNs are discrepant and exist in different wireless environments,
      which leads to various signal-to-noise ratios (SNRs) for the same or different
      licensed users. Unlicensed users bargain with licensed users regarding the
      spectrum price. In each round of bargaining, licensed users are allowed to
      adaptively adjust their spectrum price to the best for maximizing their profits.
      . Then, each unlicensed user makes their best response and informs licensed users
      of "bargaining" and "warning". Through finite rounds of bargaining, this scheme
      can obtain a Nash bargaining solution (NBS), which makes all licensed and
      unlicensed users reach an agreement. The simulation results demonstrate that the
      proposed scheme can quickly find a NBS and all players in the game prefer to be
      honest. The proposed scheme outperforms existing schemes, within a certain range,
      in terms of fairness and trade success probability.

PMID- 29186921
TI  - Analysis of Sources of Large Positioning Errors in Deterministic Fingerprinting.
AB  - Wi-Fi fingerprinting is widely used for indoor positioning and indoor navigation
      due to the ubiquity of wireless networks, high proliferation of Wi-Fi-enabled
      mobile devices, and its reasonable positioning accuracy. The assumption is that
      the position can be estimated based on the received signal strength intensity
      from multiple wireless access points at a given point. The positioning accuracy,
      within a few meters, enables the use of Wi-Fi fingerprinting in many different
      applications. However, it has been detected that the positioning error might be
      very large in a few cases, which might prevent its use in applications with high
      accuracy positioning requirements. Hybrid methods are the new trend in indoor
      positioning since they benefit from multiple diverse technologies (Wi-Fi,
      Bluetooth, and Inertial Sensors, among many others) and, therefore, they can
      provide a more robust positioning accuracy. In order to have an optimal
      combination of technologies, it is crucial to identify when large errors occur
      and prevent the use of extremely bad positioning estimations in hybrid
      algorithms. This paper investigates why large positioning errors occur in Wi-Fi
      fingerprinting and how to detect them by using the received signal strength
      intensities.

PMID- 29186920
TI  - RNA Chaperone Function of a Universal Stress Protein in Arabidopsis Confers
      Enhanced Cold Stress Tolerance in Plants.
AB  - The physiological function of Arabidopsis thaliana universal stress protein
      (AtUSP) in plant has remained unclear. Thus, we report here the functional role
      of the Arabidopsis universal stress protein, AtUSP (At3g53990). To determine how
      AtUSP affects physiological responses towards cold stress, AtUSP overexpression
      (AtUSP OE) and T-DNA insertion knock-out (atusp, SALK_146059) mutant lines were
      used. The results indicated that AtUSP OE enhanced plant tolerance to cold
      stress, whereas atusp did not. AtUSP is localized in the nucleus and cytoplasm,
      and cold stress significantly affects RNA metabolism such as by misfolding and
      secondary structure changes of RNA. Therefore, we investigated the relationship
      of AtUSP with RNA metabolism. We found that AtUSP can bind nucleic acids,
      including single- and double-stranded DNA and luciferase mRNA. AtUSP also
      displayed strong nucleic acid-melting activity. We expressed AtUSP in RL211
      Escherichia coli, which contains a hairpin-loop RNA structure upstream of
      chloramphenicol acetyltransferase (CAT), and observed that AtUSP exhibited anti
      termination activity that enabled CAT gene expression. AtUSP expression in the
      cold-sensitive Escherichia coli (E. coli) mutant BX04 complemented the cold
      sensitivity of the mutant cells. As these properties are typical characteristics
      of RNA chaperones, we conclude that AtUSP functions as a RNA chaperone under cold
      shock conditions. Thus, the enhanced tolerance of AtUSP OE lines to cold stress
      is mediated by the RNA chaperone function of AtUSP.

PMID- 29186922
TI  - An Overview of GIS-Based Modeling and Assessment of Mining-Induced Hazards: Soil,
      Water, and Forest.
AB  - In this study, current geographic information system (GIS)-based methods and
      their application for the modeling and assessment of mining-induced hazards were
      reviewed. Various types of mining-induced hazard, including soil contamination,
      soil erosion, water pollution, and deforestation were considered in the
      discussion of the strength and role of GIS as a viable problem-solving tool in
      relation to mining-induced hazards. The various types of mining-induced hazard
      were classified into two or three subtopics according to the steps involved in
      the reclamation procedure, or elements of the hazard of interest. Because GIS is
      appropriated for the handling of geospatial data in relation to mining-induced
      hazards, the application and feasibility of exploiting GIS-based modeling and
      assessment of mining-induced hazards within the mining industry could be expanded
      further.

PMID- 29186923
TI  - Adapting Local Features for Face Detection in Thermal Image.
AB  - A thermal camera captures the temperature distribution of a scene as a thermal
      image. In thermal images, facial appearances of different people under different
      lighting conditions are similar. This is because facial temperature distribution
      is generally constant and not affected by lighting condition. This similarity in
      face appearances is advantageous for face detection. To detect faces in thermal
      images, cascade classifiers with Haar-like features are generally used. However,
      there are few studies exploring the local features for face detection in thermal
      images. In this paper, we introduce two approaches relying on local features for
      face detection in thermal images. First, we create new feature types by extending
      Multi-Block LBP. We consider a margin around the reference and the generally
      constant distribution of facial temperature. In this way, we make the features
      more robust to image noise and more effective for face detection in thermal
      images. Second, we propose an AdaBoost-based training method to get cascade
      classifiers with multiple types of local features. These feature types have
      different advantages. In this way we enhance the description power of local
      features. We did a hold-out validation experiment and a field experiment. In the
      hold-out validation experiment, we captured a dataset from 20 participants,
      comprising 14 males and 6 females. For each participant, we captured 420 images
      with 10 variations in camera distance, 21 poses, and 2 appearances (participant
      with/without glasses). We compared the performance of cascade classifiers trained
      by different sets of the features. The experiment results showed that the
      proposed approaches effectively improve the performance of face detection in
      thermal images. In the field experiment, we compared the face detection
      performance in realistic scenes using thermal and RGB images, and gave discussion
      based on the results.

PMID- 29186925
TI  - Indigenous Values and Health Systems Stewardship in Circumpolar Countries.
AB  - Circumpolar regions, and the nations within which they reside, have recently
      gained international attention because of shared and pressing public policy
      issues such as climate change, resource development, endangered wildlife and
      sovereignty disputes. In a call for national and circumpolar action on shared
      areas of concern, the Arctic states health ministers recently met and signed a
      declaration that identified shared priorities for international cooperation.
      Among the areas for collaboration raised, the declaration highlighted the
      importance of enhancing intercultural understanding, promoting culturally
      appropriate health care delivery and strengthening circumpolar collaboration in
      culturally appropriate health care delivery. This paper responds to the
      opportunity for further study to fully understand indigenous values and contexts,
      and presents these as they may apply to a framework that will support
      international comparisons and systems improvements within circumpolar regions. We
      explored the value base of indigenous peoples and provide considerations on how
      these values might interface with national values, health systems values and
      value bases between indigenous nations particularly in the context of health
      system policy-making that is inevitably shared between indigenous communities and
      jurisdictional or federal governments. Through a mixed methods nominal consensus
      process, nine values were identified and described: humanity, cultural
      responsiveness, teaching, nourishment, community voice, kinship, respect, holism
      and empowerment.

PMID- 29186924
TI  - Regulation of the Tumor-Suppressor BECLIN 1 by Distinct Ubiquitination Cascades.
AB  - Autophagy contributes to cellular homeostasis through the degradation of various
      intracellular targets such as proteins, organelles and microbes. This relates
      autophagy to various diseases such as infections, neurodegenerative diseases and
      cancer. A central component of the autophagy machinery is the class III
      phosphatidylinositol 3-kinase (PI3K-III) complex, which generates the signaling
      lipid phosphatidylinositol 3-phosphate (PtdIns3P). The catalytic subunit of this
      complex is the lipid-kinase VPS34, which associates with the membrane-targeting
      factor VPS15 as well as the multivalent adaptor protein BECLIN 1. A growing list
      of regulatory proteins binds to BECLIN 1 and modulates the activity of the PI3K
      III complex. Here we discuss the regulation of BECLIN 1 by several different
      types of ubiquitination, resulting in distinct polyubiquitin chain linkages
      catalyzed by a set of E3 ligases. This contribution is part of the Special Issue
      "Ubiquitin System".

PMID- 29186927
TI  - Estimating Free and Added Sugar Intakes in New Zealand.
AB  - The reduction of free or added sugar intake (sugars added to food and drinks as a
      sweetener) is almost universally recommended to reduce the risk of obesity
      related diseases and dental caries. The World Health Organisation recommends
      intakes of free sugars of less than 10% of energy intake. However, estimating and
      monitoring intakes at the population level is challenging because free sugars
      cannot be analytically distinguished from naturally occurring sugars and most
      national food composition databases do not include data on free or added sugars.
      We developed free and added sugar estimates for the New Zealand (NZ) food
      composition database (FOODfiles 2010) by adapting a method developed for
      Australia. We reanalyzed the 24 h recall dietary data collected for 4721 adults
      aged 15 years and over participating in the nationally representative 2008/09 New
      Zealand Adult Nutrition Survey to estimate free and added sugar intakes. The
      median estimated intake of free and added sugars was 57 and 49 g/day respectively
      and 42% of adults consumed less than 10% of their energy intake from free sugars.
      This approach provides more direct estimates of the free and added sugar contents
      of New Zealand foods than previously available and will enable monitoring of
      adherence to free sugar intake guidelines in future.

PMID- 29186928
TI  - Metabolites Produced by an Endophytic Phomopsis sp. and Their Anti-TMV Activity.
AB  - The fermentation and isolation of metabolites produced by an endophytic fungus,
      which was identified as Phomopsis sp. FJBR-11, based on phylogenetic analysis,
      led to the identification of six compounds, including dothiorelones A-C, and H,
      and cytosporones C and U. Among these compounds, cytosporone U exhibited potent
      inhibitory activity against Tobacco mosaic virus (TMV). Moreover, the crude and a
      purified exopolysaccharide were proved to possess strong inhibitory effects
      against the virus infection.

PMID- 29186926
TI  - Structural Diversity and Biological Activities of Fungal Cyclic Peptides,
      Excluding Cyclodipeptides.
AB  - Cyclic peptides are cyclic compounds formed mainly by the amide bonds between
      either proteinogenic or non-proteinogenic amino acids. This review highlights the
      occurrence, structures and biological activities of fungal cyclic peptides
      (excluding cyclodipeptides, and peptides containing ester bonds in the core ring)
      reported until August 2017. About 293 cyclic peptides belonging to the groups of
      cyclic tri-, tetra-, penta-, hexa-, hepta-, octa-, nona-, deca-, undeca-, dodeca
      , tetradeca-, and octadecapeptides as well as cyclic peptides containing ether
      bonds in the core ring have been isolated from fungi. They were mainly isolated
      from the genera Aspergillus, Penicillium, Fusarium, Acremonium and Amanita. Some
      of them were screened to have antimicrobial, antiviral, cytotoxic, phytotoxic,
      insecticidal, nematicidal, immunosuppressive and enzyme-inhibitory activities to
      show their potential applications. Some fungal cyclic peptides such as the
      echinocandins, pneumocandins and cyclosporin A have been developed as
      pharmaceuticals.

PMID- 29186930
TI  - Protective Effects of Liquiritigenin against Citrinin-Triggered, Oxidative-Stress
      Mediated Apoptosis and Disruption of Embryonic Development in Mouse Blastocysts.
AB  - The mycotoxin citrinin (CTN), a natural contaminant in foodstuffs and animal
      feeds, exerts cytotoxic and genotoxic effects on various mammalian cells and
      embryos. A previous investigation by our group revealed potentially hazardous
      effects of CTN on mouse oocyte maturation and pre- and post-implantation embryo
      development via the induction of apoptosis. The present study showed that CTN
      induces apoptosis and inhibits cell proliferation in the inner cell mass of mouse
      blastocysts. Notably, we observed for the first time that both these effects are
      suppressed by liquiritigenin (LQ). LQ is a type of flavonoid isolated from
      Glycyrrhiza radix with several biochemical and pharmacological activities,
      including antioxidant and anti-inflammatory properties. The preincubation of
      blastocysts with LQ clearly prevented CTN-induced disruption of pre- and post
      implantation embryonic development and fetal weight loss, both in vitro and in
      vivo. CTN-induced damage processes directly promoted reactive oxygen species
      (ROS) generation, loss of mitochondrial membrane potential (MMP) and activation
      of caspase-9 and caspase-3, which were effectively blocked by LQ. Moreover, in an
      animal model, intravenous injection of dams with CTN (3 mg/kg/day) triggered
      apoptosis of blastocysts, disruption of embryonic development from the zygote to
      the blastocyst stage and a decrease in fetal weight. Pre-injection with LQ (5
      mg/kg/day) effectively reduced apoptosis and impaired the cytotoxic effects of
      CTN on development. Our in vivo findings further confirm that CTN exposure via
      injection has the potential to impair pre- and post-implantation development,
      leading to apoptosis and the suppression of sequent embryonic development, which
      can be effectively prevented by LQ.

PMID- 29186931
TI  - Mixture Toxicity of Bensulfuron-Methyl and Acetochlor to Red Swamp Crayfish
      (Procambarus clarkii): Behavioral, Morphological and Histological Effects.
AB  - The mixture of bensulfuron-methyl and acetochlor (MBA) has been widely applied as
      a rice herbicide in China, but the mixture toxicity of MBA to aquatic organisms
      is largely unknown. The current study aims to investigate the acute effects of
      MBA to juvenile red swamp crayfish, Procambarus clarkii. Firstly, a 96 h semi
      static exposure was conducted to determine the Lethal Concentration 50 (LC50)
      values at 24, 48, 72 and 96 h, as well as to assess the behavioral and
      morphological effects. A second 96 h exposure was conducted at an MBA
      concentration of 50% of the 96 h LC50 (72.62 mg/L) to assess the histological
      changes in the gill, perigastric organ, muscle, heart, stomach, and midgut. The
      results showed that MBA exhibited low acute toxicity with the 24, 48, 72 and 96 h
      LC50 values of 191.25 (179.37-215.75), 166.81 (159.49-176.55), 154.30 (148.36
      160.59) and 145.24 (138.94-151.27) mg/L, respectively. MBA-exposed crayfish
      showed body jerk, belly arch, equilibrium loss, body and appendage sway, and
      lethargy; and the dead crayfish showed dark gray or grayish-white body color and
      separated cephalothorax and abdomen. At 72.62 mg/L, MBA exposure caused
      significant histopathological alterations, mainly including the cuticular and
      epithelial degeneration of all the gills; atrophy of tubule lumina and cellular
      vacuolation of the perigastric organs (61.15 +/- 9.90% of the tubules showed
      lesions); epithelial hyperplasia (48.40 +/- 9.00%), myocardial fibers and
      epithelial cell lysis (17.30 +/- 2.01%), and hemocytic infiltration of the
      hearts; cuticular swelling (15.82 +/- 2.98%) and vacuolate connective tissue
      (11.30 +/- 2.47%) of the stomachs; atrophied bladder cell and fragmented
      longitudinal muscles (95.23 +/- 4.77%) of the midguts; and slight myofibers
      fragmentation and lysis (7.37 +/- 0.53%) of the abdominal muscles. Our results
      indicate that MBA can cause behavioral, morphological and histopathological
      effects on juvenile P. clarkii at relatively high concentrations, but its acute
      toxicity is low compared with many other common herbicides.

PMID- 29186932
TI  - Ionic Substitutions in Non-Apatitic Calcium Phosphates.
AB  - Calcium phosphate materials (CaPs) are similar to inorganic part of human
      mineralized tissues (i.e., bone, enamel, and dentin). Owing to their high
      biocompatibility, CaPs, mainly hydroxyapatite (HA), have been investigated for
      their use in various medical applications. One of the most widely used ways to
      improve the biological and physicochemical properties of HA is ionic substitution
      with trace ions. Recent developments in bioceramics have already demonstrated
      that introducing foreign ions is also possible in other CaPs, such as tricalcium
      phosphates (amorphous as well as alpha and beta crystalline forms) and brushite.
      The purpose of this paper is to review recent achievements in the field of non
      apatitic CaPs substituted with various ions. Particular attention will be focused
      on tricalcium phosphates (TCP) and "additives" such as magnesium, zinc,
      strontium, and silicate ions, all of which have been widely investigated thanks
      to their important biological role. This review also highlights some of the
      potential biomedical applications of non-apatitic substituted CaPs.

PMID- 29186934
TI  - Joint Decision-Making and the Coordination of a Sustainable Supply Chain in the
      Context of Carbon Tax Regulation and Fairness Concerns.
AB  - Carbon tax regulation and consumers' low-carbon preference act as incentives for
      firms to abate emissions. Manufacturers can improve product sustainability and
      retailers can strengthen the promotion of low-carbon products as part of such
      abatement. Current incomplete rationality also affects product sustainability and
      low-carbon promotion level. In this context, we consider a supply chain with a
      manufacturer and a retailer and investigate the impacts of the manufacturer's and
      the retailer's fairness concerns on their production sustainability level, low
      carbon promotion level and profitability. We also explore the coordination
      contract. The results show that the manufacturer's and the retailer's fairness
      concerns decrease their product sustainability and low-carbon promotion level,
      together with the profits of the system and the manufacturer. With regard to the
      retailer's fairness concern, the product sustainability level and the
      manufacturer's profit are lower; moreover, the low-carbon promotion level and the
      profits of the supply chain and the retailer are higher. A revenue-sharing
      contract can coordinate the supply chain perfectly; however, members' fairness
      concerns increase the difficulty of coordination. Finally, the numerical results
      reveal that carbon tax regulation can encourage the manufacturer to enhance the
      product sustainability level. Further, the impacts on the low-carbon promotion
      level and firms' profitability are related to the cost coefficients of product
      sustainability.

PMID- 29186933
TI  - Targeting Autophagy in ALK-Associated Cancers.
AB  - Autophagy is an evolutionarily conserved catabolic process, which is used by the
      cells for cytoplasmic quality control. This process is induced following
      different kinds of stresses e.g., metabolic, environmental, or therapeutic, and
      acts, in this framework, as a cell survival mechanism. However, under certain
      circumstances, autophagy has been associated with cell death. This duality has
      been extensively reported in solid and hematological cancers, and has been
      observed during both tumor development and cancer therapy. As autophagy plays a
      critical role at the crossroads between cell survival and cell death, its
      involvement and therapeutic modulation (either activation or inhibition) are
      currently intensively studied in cancer biology, to improve treatments and
      patient outcomes. Over the last few years, studies have demonstrated the
      occurrence of autophagy in different Anaplastic Lymphoma Kinase (ALK)-associated
      cancers, notably ALK-positive anaplastic large cell lymphoma (ALCL), non-small
      cell lung carcinoma (NSCLC), Neuroblastoma (NB), and Rhabdomyosarcoma (RMS). In
      this review, we will first briefly describe the autophagic process and how it can
      lead to opposite outcomes in anti-cancer therapies, and we will then focus on
      what is currently known regarding autophagy in ALK-associated cancers.

PMID- 29186929
TI  - Integrated Immunomodulatory Mechanisms through which Long-Chain n-3
      Polyunsaturated Fatty Acids Attenuate Obese Adipose Tissue Dysfunction.
AB  - Obesity is a global health concern with rising prevalence that increases the risk
      of developing other chronic diseases. A causal link connecting overnutrition, the
      development of obesity and obesity-associated co-morbidities is visceral adipose
      tissue (AT) dysfunction, characterized by changes in the cellularity of various
      immune cell populations, altered production of inflammatory adipokines that
      sustain a chronic state of low-grade inflammation and, ultimately, dysregulated
      AT metabolic function. Therefore, dietary intervention strategies aimed to halt
      the progression of obese AT dysfunction through any of the aforementioned
      processes represent an important active area of research. In this connection,
      fish oil-derived dietary long-chain n-3 polyunsaturated fatty acids (PUFA) in the
      form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been
      demonstrated to attenuate obese AT dysfunction through multiple mechanisms,
      ultimately affecting AT immune cellularity and function, adipokine production,
      and metabolic signaling pathways, all of which will be discussed herein.

PMID- 29186935
TI  - Adult Nutrient Intakes from Current National Dietary Surveys of European
      Populations.
AB  - The World Health Organization (WHO) encourages countries to undertake national
      dietary survey (NDS) but implementation and reporting is inconsistent. This paper
      provides an up-to-date review of adult macro and micronutrient intakes in
      European populations as reported by NDS. It uses WHO Recommended Nutrient Intakes
      (RNIs) to assess intake adequacy and highlight areas of concern. NDS information
      was gathered primarily by internet searches and contacting survey authors and
      nutrition experts. Survey characteristics and adult intakes by gender/age group
      were extracted for selected nutrients and weighted means calculated by region. Of
      the 53 WHO Europe countries, over a third (n = 19), mainly Central & Eastern
      European countries (CEEC), had no identifiable NDS. Energy and nutrient intakes
      were extracted for 21 (40%) countries but differences in age group, methodology,
      under-reporting and nutrient composition databases hindered inter-country
      comparisons. No country met more than 39% WHO RNIs in all age/gender groups;
      macronutrient RNI achievement was poorer than micronutrient. Overall RNI
      attainment was slightly worse in CEEC and lower in women and female elderly. Only
      40% countries provided adult energy and nutrient intakes. The main gaps lie in
      CEEC, where unknown nutrient deficiencies may occur. WHO RNI attainment was
      universally poor for macronutrients, especially for women, the female elderly and
      CEEC. All countries could be encouraged to report a uniform nutrient set and sub
      analyses of nationally representative nutrient intakes.

PMID- 29186936
TI  - Endoscope-Assisted Cochlear Implantation.
AB  - OBJECTIVES: Our aim was to present our endoscope-assisted cochlear implantation
      (CI) technique, in which the middle ear landmarks were identified through the
      facial recess exposure by using an endoscopic view without elevating the tympanic
      annulus. The secondary goal was to assess whether the situation of difficult
      surgical exposure could be predicted by evaluating preoperative axial computed
      tomography (CT) examinations. METHODS: CT examinations and surgical outcomes of
      endoscope-assisted CI surgeries were analyzed. RESULTS: A total of 179 CI
      operations performed in 27 adults (15.1%) and 152 children (84.9%) were
      retrospectively evaluated. It was found that in 14 cases (7.8%), endoscopic
      examination contributed substantially in identifying the round window (RW)
      membrane correctly. Endoscopic identification of the RW through the posterior
      tympanotomy enabled us to perform a straightforward surgery in all these cases,
      without the need for switching to a bony cochleostomy or alternative surgical
      techniques. The difficulty in the surgical exposure was predicted preoperatively
      by examining the axial CT scans in six of the 14 cases (42.8%) for which
      endoscopic assistance was necessary in order to identify the RW correctly.
      CONCLUSION: The main benefit of endoscope-assisted CI is the improved visibility
      leading to a panoramic view of the RW region. The implementation of transfacial
      recess endoscopic examination into the conventional CI technique is helpful to
      avoid problems during surgical orientation. However, the difficulty in the
      surgical exposure of the RW cannot be reliably predicted by the subjective
      evaluation of preoperative CT scans and more studies are needed to obtain
      reliable criteria.

PMID- 29186937
TI  - How to use PET/CT in the evaluation of response to radiotherapy.
AB  - Radiotherapy is a major treatment modality for many cancers. Tumor response after
      radiotherapy determines the subsequent steps of the patient's management
      (surveillance, adjuvant or salvage treatment and palliative care). Tumor response
      assessed during radiotherapy offers a promising opportunity to adapt the
      treatment plan to reduced or increased target volume, to specifically target sub
      volumes with relevant biological characteristics (metabolism, hypoxia,
      proliferation, etc.) and to further spare the organs at risk. In addition to its
      role in the diagnosis and the initial staging, Positron Emission Tomography
      combined with a Computed Tomography (PET/CT) provides functional information and
      is therefore attractive to evaluate tumor response. The aim of this paper is to
      review the published data addressing PET/CT as an evaluation tool in irradiated
      tumors. Reports on PET/CT acquired at various times (during radiotherapy, after
      initial (chemo-) radiotherapy, after definitive radiotherapy and during
      posttreatment follow-up) in solid tumors (lung, head-and-neck, cervix, esophagus,
      prostate and rectum) were collected and reviewed. Various tracers and technical
      aspects are also discussed. 18F-FDG PET/CT has a well-established role in
      clinical routine after definitive chemo-radiotherapy for locally advanced head
      and-neck cancers. 18F-choline PET/CT is indicated in prostate cancer patients
      with biochemical failure. 18F-FDG PET/CT is optional in many other circumstances
      and the clinical benefits of assessing tumor response with PET/CT remain a field
      of very active research. The combination of PET with Magnetic Resonance Imaging
      (PET/MRI) may prove to be valuable in irradiated rectal and cervix cancers. Tumor
      response can be evaluated by PET/CT with clinical consequences in multiple
      situations, notably in head and neck and prostate cancers, after radiotherapy.
      Further clinical evaluation for most cancers is still needed, possibly in
      association to MRI.

PMID- 29186938
TI  - Occurrence and clinical characteristics of hepatocellular carcinoma in the north
      eastern Poland
AB  - : Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the
      third leading cause of cancerrelatedmortality worldwide. Risk factors for this
      malignancy include liver cirrhosis, HBV or HCV infection,fatty liver disease. THE
      AIM OF STUDY: This study aims to assess the occurrence and clinical
      characteristics of HCC in theNortheastern Poland between 2011 and 2015. The
      number of primary lesions, their size and location within theliver were analysed.
      The risk factors for this cancer in studied population have been identified. The
      usefulnessof AFP screening and imaging studies for the diagnosis of HCC were
      assessed. A preliminary analysis of theefficacy of anti-tumour therapy was
      performed. RESULTS: Sixty-seven patients (28% female and 72% male) with diagnosed
      HCC were enrolled. HCC diagnosiswas established according to the criteria
      proposed by the International Consensus Group for Hepatocellular Neoplasia.Of the
      67 patients in the study, 7 (10%) were aged 30 to 50 years and 60 patients (90%)
      were aged 51 years and older.During the period 2011-2015, an increase in HCC
      incidence was observed. In studied group the most prevalent (31%)were patients
      with 2 tumours localised in the 6th, 7th or 8th segments of the liver. Metastatic
      tumours were presentin 15% and portal vein thrombosis in 9% of patients. Risk
      factors assessment revealed that in 72% of patients HCCcoexisted with cirrhosis,
      33% of patients were HCV-infected, 30% had HBV infection, and 15% were
      diagnosedwith NASH. Elevated serum AFP level was observed in 83% of patients with
      liver cirrhosis, and in 58% of patientswithout cirrhosis (p <0.05). Liver
      transplantation was the best therapeutic option. The efficacy of
      ablation/resection incombination with sorafenib vs. ablation/partial resection
      was comparable. CONCLUSION: There has been an increase in the number of HCC cases
      in North-eastern Poland in last fewyears. HCC is more common in men aged 50 years
      and older. Increased serum AFP level is a useful marker forthe diagnosis and
      monitoring of HCC treatment in patients with liver cirrhosis.

PMID- 29186939
TI  - Periapical abscess - etiology, pathogenesis and epidemiology
AB  - Inflammation of the pulp and periapical tissues is the main cause of tooth loss
      in patients worldwide, therefore endodontics is one of the most rapidly
      developing specialties in dentistry. Despite proper endodontic treatment, in many
      cases it is not possible to determine the etiology of infection or the reason for
      its relapse.Many research studies indicate that infections of the periapical
      tissues are mainly caused by strictly anaerobic bacteria. At present, more and
      more often the composition of the microflora within the inflammatory lesions is
      being evaluated with the use of molecular techniques, which showed that classical
      culture methods are not able to determine the etiology of infections of the
      periapical tissues. The results of these studies contributed to the major changes
      in our  understanding of the microbiome composition in the endodontium. Purulent
      endodontic lesions are particularly important, as they may lead to many severe -
      even life-threatening - systemic complications.

PMID- 29186940
TI  - Patient's health awareness as a significant link in the process of melanoma
      diagnostics
AB  - INTRODUCTION: Melanoma malignum is a relatively rare neoplasm, among all skin
      neoplasms, but its relatedmortality is high. Diagnosis and removal of the lesion
      at an early stage are crucial for significant increase inchances of survival
      andis highly determined by patients' awareness in terms of melanoma risk factors.
      AIM: The aim of the study was to determine the level of patients' knowledge and
      awareness in terms of skinmelanoma, its risk factors, health promoting behaviors,
      as well as learning about the sources of this knowledge. MATERIAL AND METHODS:
      Study group included 142 patients from the Department of Dermatology at
      theUniversity Hospital in Krakow. Patients were divided into two groups: 88
      people from the VideodermatoscopyOffice (VDO), 53 people from other offices (OO).
      A questionnaire including 40 questions was used as a researchtool for the studied
      group. It applied to data obtained from demographic data, determination of skin
      phototypeaccording to Fitzpatrick scale, history of possible suspicious or
      removed skin lesions, awareness in terms ofskin neoplasm prevention, patients'
      knowledge about skin melanoma, and its source. Collected data were thensubjected
      to statistical analysis. RESULTS: VDO patients provided more accurate answers to
      questions regarding melanoma, prognosis, risk factors,possible melanoma sites,
      and treatment. Melanoma was correctly described as a malignant neoplasm by 92%
      peoplefrom the VDO group, and 65% of the OO group, surgical melanoma removal as
      the correct method was indicated by84% vs. 68% and excessive exposure to sunlight
      88.2% vs. 74%, sunbathing without use of skin sunscreen lotions92.1% vs. 84%,
      melanoma in the family 75% vs. 66%, use of tanning salons 80.3% vs. 66%, exposure
      to excessive suneffect during childhood 67.1% vs. 34%, previously removed
      melanoma 44.7% vs. 24%, use of tanning beds 80.3% vs.66%, high number of nevi
      68.4% vs. 38% as melanoma risk factors, features of alarming nevi (multiple
      colors 77.3%vs. 56.6%, growth over time 75% vs. 50.9%, irregular borders 72.7%
      vs. 45.3%, diameter >5 mm 72.7% vs. 45.3%,asymmetrical shape 61.4% vs. 67.9%).
      51.3% of patients of the VDO vs. 8% of the OO group indicated physician asthe
      source of knowledge and 79,1% vs. 61% of them perform regular self-examination.
      CONCLUSION: Crucial links in the process of melanoma diagnostics include: health
      awareness of patients,involvement of physicians, both dermatologists, and primary
      healthcare physicians, as well as appropriatelyprepared and comprehensive
      information and education provided by media. According to the foregoing
      information,physicians have to be ready not only to diagnose the problem reported
      by a patient, but also to take theinitiative and educate patients in terms of
      disease character, risk factors and motivating to perform self-examinationof the
      skin, as this provides the most measurable results.

PMID- 29186941
TI  - Is one minute enough to convince parents to vaccinate their child?
AB  - INTRODUCTION: A growing number of parents refuse childhood vaccination. This
      situation may be causedby many reasons, but surely the lack of parental knowledge
      is one of them. A physician, as the most reliablesource of information about
      vaccination, plays an important role in parental education. How can we
      successfullyinform parents about vaccinations, when faced with primary care visit
      being too short? The aim of this studywas to assess the impact of three types of
      information about pneumococcal vaccine on parental decision-making. MATERIAL AND
      METHODS: The children were enrolled based on the inclusion and exclusion
      criteria. Theparents received one of three types of vaccination information:
      simple oral, extent oral and written one. The endpointof the study was the length
      of time between the day parents were informed by physician and the day firstdose
      of vaccine was administered. RESULTS: The percentage of vaccinated children was:
      12.8% for written information, 14.7% for extended and20.8% for simple one. The
      simple information was significantly associated with increased chances for
      vaccinationin the following groups: children with a birth weight <3355 g
      (p<0.025), born with a gestational age <40weeks (p<0.015) and in the group with
      lower healthcare utilization (p<0.020). The extended information wassignificantly
      associated with increased chances for vaccination in the group of chronically ill
      mothers (p<0.045). CONCLUSIONS: Physicians should provide parents with
      personalized immunization information. One minutemay be sufficient to convince
      parents to vaccinate their child, especially if healthcare utilization of family
      is low.Chronically ill parents should be given extended information. Discussion
      about vaccinations with parents shouldnot be replaced by written vaccination
      information.

PMID- 29186942
TI  - Methods of testing repellent efficiency against ticks
AB  - The use of repellents is the most important in the tick-bite protection. The
      tests of repellents efficiency shall give strict answer whether ticks are
      repelled effectively or not by a given agent. Methods of testing repellent
      efficiency can be divided in in three groups: experiments without tick host and
      host stimuli; studies simulating host stimuli, methods of testing repellents on
      animals or human volunteers. Studies on protected human volunteers are the
      nearest practical conditions of repellent use. However, there is sometimes a need
      of testing products with unknown toxicity to man; in such circumstances their
      efficiency should be evaluated in experiments in simulated human body conditions
      but without a person.

PMID- 29186943
TI  - Modified minimally invasive direct anterior approach through a bikini incision
      for total hip arthroplasty: technique and results in young female patients.
AB  - Direct anterior approach for THA has gained popularity over the last years.
      However, concerns have been raised regarding the cosmetic, related to the
      incision that does not respect the Langer's skin tension line and may produce
      hypertrophic scars. The aim of this study was to analyze the preliminary results
      in 22 young female patients undergoing THA through a minimally invasive direct
      anterior approach using a modified oblique bikini incision. Clinical evaluations
      showed an improvement of WOMAC, UCLA and Harris Hip Score at 5-month follow-up.
      The technique ensured proper implant positioning and showed advantages in terms
      of complications, transfusion rates, hospital length of stay and functional
      recovery. From the aesthetic point of view, the expected cosmetic results were
      obtained. Minimally invasive direct anterior approach using a modified oblique
      bikini incision represent a viable option for THA, combining both the advantages
      of a minimal invasive procedure with a better aesthetic appearance.

PMID- 29186944
TI  - Direct vertebral rotation and differently shaped dual rod translation technique
      in adolescent idiopathic scoliosis.
AB  - Direct vertebral rotation (DVR) is widely used to correct the axial deformity in
      adolescent idiopathic scoliosis (AIS). Indirect rotation techniques may help DVR
      in order to improve outcome. Vertebral translation technique combined with the
      use of two differently shaped rods resulted effective in reducing the rib hump
      deformity. The aim of this study is to describe the technique and evaluate the
      efficacy of combined DVR and vertebral translation technique on axial deformity
      correction. Mean follow-up was 2.7 years. Cobb angle, kyphosis angle, apical
      vertebrae axial rotation angle, SRS-22 questionnaire of 30 AIS patients treated
      with combined DVR and differently shaped dual rods translation technique were
      collected and compared preoperatively and postoperatively. At the last follow-up
      no screw pull-out, nonunion or loss of correction were recorded. The combination
      of DVR and differently shaped dual rods translation technique in AIS can provide
      good three-dimensional correction and improvement of patient's quality of life.

PMID- 29186945
TI  - Correlation between gamma glutamyltransferase fractions and bone quality.
AB  - Gamma-glutamyltransferase (GGT) has been recently identified as a bone-resorbing
      factor. The aim of this study was to investigate the association between plasma
      GGT fractions levels and bone quality. Plasma GGT fractions were analysed by gel
      filtration chromatography. Bone quality was established quantitatively by two
      micro-CT derived microarchitectural parameters: the BV/TV (mineralised bone
      volume/total volume), and the SMI (structure model index) that describes the rod
      like (low resistant) or plate-like (high-resistant) shape of bone trabeculae. We
      enrolled 93 patients hospitalised for elective total hip replacement (group
      Arthrosis, n=46) or for proximal femoral fracture (group Fracture, n=47).
      Patients within the first quartile of BV/TV (Q1, osteoporotic patients, n=6)
      showed higher levels of b-GGT fraction [median (min-max): 3.37 (1.42-6.81)]
      compared to patients with normal bone density (fourth quartile Q4, n=10; 1.40
      (0.83-4.36); p=0.0393]. Also, according to SMI, b-GGT value was higher in the
      subgroup with bone fragility [Q1, n=8: 1.36 (0.43-4.36); Q4, n=8: 5.10 (1.4 
      7.60); p=0.0117]. In conclusion, patients characterised by fragile bone structure
      showed specifically higher levels of plasma b-GGT activity thus suggesting
      fractional GGT analysis as a possible biomarker in the diagnosis of osteoporosis.

PMID- 29186946
TI  - Use of autologous bone marrow cells concentrate enriched with platelet-fibrin on
      extensor mechanism allograft reconstruction for extensor mechanism failure
      following total knee arthroplasty.
AB  - Allografts techniques remain the best reconstructive strategy for chronic
      extensor mechanism lesions after total knee arthroplasty (3) but outcomes depend
      strictly on the host tissue-allograft junctions healing. The purpose of this
      study is to evaluate if modern techniques of adding autologous bone marrow cells
      concentrate enriched with platelet-rich fibrin, provide better healing of the
      allograft. We present the case of an 86 years old patient affected by patellar
      tendon rupture after TKA. A whole extensor mechanism allograft was performed
      adding a bone marrow cells concentrate enriched with platelet-rich fibrin on the
      host tissue-allograft junctions. Preoperatively and at each follow-up the value
      of Knee Society Score and radiographic consolidation signs were recorded.
      Radiographic controls showed clear signs of consolidation already at 1 months
      follow-up and a solid fusion at 3 months. This case report describes a valid
      method to improve healing using a tissue-construct engineered with stem cells and
      growth factors.

PMID- 29186947
TI  - One-step cartilage repair with minced chondral fragment on a composite scaffold:
      an in vitro human study at low oxygen tension.
AB  - Minced cartilage fragments are a viable cell source for one stage cartilage
      repair. However, the joint surface is a low oxygen tension microenvironment and
      little evidence is present in literature regarding the behaviour of cartilage
      fragments in this peculiar condition. The aim of the study is i) to verify if low
      oxygen tension could negatively influence chondrocyte outgrowth from cartilage
      fragments into a Hyaluronic-Acid(HA)/fibrin scaffold and ii) to evaluate its
      effects on the behaviour of migrating chondrocyte, compared to normoxic
      condition. A slight decrease in chondrocyte migration and proliferation was
      observed in low oxygen tension cultures. Conversely, an increase in the
      expression of SOX9, beta-catenin, HIFs, collagen-I and II (p<0.05) in migrating
      chondrocytes from low oxygen tension cultures was present. Thus, a long term-
      exposure at low oxygen tension seems to improve the chondrocytic phenotype
      expression of cell outgrowing from cartilage fragments onto a HA/fibrin scaffold.

PMID- 29186948
TI  - Bone cement implantation syndrome: a thromboelastographic study of the effect of
      bone cement on coagulation.
AB  - Bone cement implantation syndrome (BCIS) is a rare form of intraoperative
      pulmonary embolism (EP) that occurs during cementation. It can be explained by
      two main theories: the monomer mediated model and the mechanic model. Our goal is
      to evaluate thromboelastographic changes in patients undergoing surgery for
      femoral neck fractures. We recruited 32 patients with a femoral neck fracture.
      The average age was 81.91 years (range 62-95). The patients were divided in two
      different groups: cemented hip arthroplasty (CC, 13 patients) and other surgical
      non-cemented techniques (SC, non-cemented hip arthroplasty, osteosynthesis). The
      coagulation was evaluated by TEG in the early pre-operatory (time A) and post
      operatory (time B), both on native blood and on blood added with Heparinase. We
      used the t-test to compare the differences between the two groups. The
      coagulation index CI was modified on hypercoagulability by surgery in both
      groups, but without statistical significance between the two groups (p>0.05). R
      parameter decreases between time A and time B in the same way in both groups
      (p>0.05). Parameter MA had no major variations between time A and B, without
      statistical significance (p>0.05). From our study it is evident that although the
      surgery would result in a change in the layout of the TEG toward
      hypercoagulability, this is similar both in cemented and non-cemented surgical
      interventions for femoral neck fractures in elderly patients. An altered
      coagulation does not appear to be the cause or a factor in determining the BCIS.

PMID- 29186949
TI  - Part by Part: Synthetic Biology Parts Used in Solventogenic Clostridia.
AB  - The solventogenic Clostridia are of interest to the chemical industry because of
      their natural ability to produce chemicals such as butanol, acetone and ethanol
      from diverse feedstocks. Their use as whole cell factories presents multiple
      metabolic engineering targets that could lead to improved sustainability and
      profitability of Clostridium industrial processes. However, engineering efforts
      have been held back by the scarcity of genetic and synthetic biology tools. Over
      the past decade, genetic tools to enable transformation and chromosomal
      modifications have been developed, but the lack of a broad palette of synthetic
      biology parts remains one of the last obstacles to the rapid engineered
      improvement of these species for bioproduction. We have systematically reviewed
      existing parts that have been used in the modification of solventogenic
      Clostridia, revealing a narrow range of empirically chosen and nonengineered
      parts that are in current use. The analysis uncovers elements, such as promoters,
      transcriptional terminators and ribosome binding sites where increased
      fundamental knowledge is needed for their reliable use in different applications.
      Together, the review provides the most comprehensive list of parts used and also
      presents areas where an improved toolbox is needed for full exploitation of these
      industrially important bacteria.

PMID- 29186950
TI  - Descriptor Data Bank (DDB): A Cloud Platform for Multiperspective Modeling of
      Protein-Ligand Interactions.
AB  - Protein-ligand (PL) interactions play a key role in many life processes such as
      molecular recognition, molecular binding, signal transmission, and cell
      metabolism. Examples of interaction forces include hydrogen bonding, hydrophobic
      effects, steric clashes, electrostatic contacts, and van der Waals attractions.
      Currently, a large number of hypotheses and perspectives to model these
      interaction forces are scattered throughout the literature and largely forgotten.
      Instead, had they been assembled and utilized collectively, they would have
      substantially improved the accuracy of predicting binding affinity of protein
      ligand complexes. In this work, we present Descriptor Data Bank (DDB), a data
      driven platform on the cloud for facilitating multiperspective modeling of PL
      interactions. DDB is an open-access hub for depositing, hosting, executing, and
      sharing descriptor extraction tools and data for a large number of interaction
      modeling hypotheses. The platform also implements a machine-learning (ML) toolbox
      for automatic descriptor filtering and analysis and scoring function (SF) fitting
      and prediction. The descriptor filtering module is used to filter out irrelevant
      and/or noisy descriptors and to produce a compact subset from all available
      features. We seed DDB with 16 diverse descriptor extraction tools developed in
      house and collected from the literature. The tools altogether generate over 2700
      descriptors that characterize (i) proteins, (ii) ligands, and (iii) protein
      ligand complexes. The in-house descriptors we extract are protein-specific which
      are based on pairwise primary and tertiary alignment of protein structures
      followed by clustering and trilateration. We built and used DDB's ML library to
      fit SFs to the in-house descriptors and those collected from the literature. We
      then evaluated them on several data sets that were constructed to reflect real
      world drug screening scenarios. We found that multiperspective SFs that were
      constructed using a large number of diverse DDB descriptors capturing various PL
      interactions in different ways outperformed their single-perspective counterparts
      in all evaluation scenarios, with an average improvement of more than 15%. We
      also found that our proposed protein-specific descriptors improve the accuracy of
      SFs.

PMID- 29186951
TI  - Exposure Assessment of Acetamide in Milk, Beef, and Coffee Using Xanthydrol
      Derivatization and Gas Chromatography/Mass Spectrometry.
AB  - Acetamide has been classified as a possible human carcinogen, but uncertainties
      exist about its levels in foods. This report presents evidence that thermal
      decomposition of N-acetylated sugars and amino acids in heated gas chromatograph
      injectors contributes to artifactual acetamide in milk and beef. An alternative
      gas chromatography/mass spectrometry protocol based on derivatization of
      acetamide with 9-xanthydrol was optimized and shown to be free of artifactual
      acetamide formation. The protocol was validated using a surrogate analyte
      approach based on d3-acetamide and applied to analyze 23 pasteurized whole milk,
      44 raw sirloin beef, and raw milk samples from 14 different cows, and yielded
      levels about 10-fold lower than those obtained by direct injection without
      derivatization. The xanthydrol derivatization procedure detected acetamide in
      every food sample tested at 390 +/- 60 ppb in milk, 400 +/- 80 ppb in beef, and
      39 000 +/- 9000 ppb in roasted coffee beans.

PMID- 29186952
TI  - Discovery of New 2-[(4,6-Dimethoxy-1,3,5-triazin-2-yl)oxy]-6-(substituted
      phenoxy)benzoic Acids as Flexible Inhibitors of Arabidopsis thaliana
      Acetohydroxyacid Synthase and Its P197L Mutant.
AB  - In the search for new antiresistance acetohydroxyacid synthase (AHAS, EC 2.2.1.6)
      inhibitors to combat weed resistance associated with AHAS mutations, a series of
      2-[(4,6-dimethoxy-1,3,5-triazin-2-yl)oxy]-6-(substituted phenoxy)benzoic acids 11
      38 were designed and synthesized via the strategy of conformational flexibility
      analysis. Compounds 21, 22, 26, 33, 36, and 38 with high potency against both
      wild-type AtAHAS and its P197L mutant were identified as promising candidates
      with low resistance factors (RF, defined as the ratio between the ki values
      toward P197L mutant and wild-type AHAS) ranging from 0.73 to 6.32. Especially,
      compound 22 (RF = 0.73) was further identified as the most potent antiresistance
      AHAS inhibitor because of its significantly reduced resistance level compared
      with that of tribenuron-methyl (RF = 2650) and bispyribac (RF = 4.57).
      Furthermore, compounds 26, 33, 36, and 38 also displayed promising herbicidal
      activities against sensitive and resistant (P197L) Descurainia sophia at the
      dosage of 75-150 g of active ingredient (ai)/ha. Notably, compounds 33 and 38
      still maintained over 60% herbicidal activity toward the resistant weed even at
      much lower dosages (37.5 g ai/ha). Therefore, the designed scaffold has the great
      potential to discover new candidate compounds for the control of weed resistance
      associated with AHAS mutation.

PMID- 29186953
TI  - Direct Detection of OXA-48 Carbapenemase Gene in Lysate Samples through Changes
      in Mechanical Properties of DNA Monolayers upon Hybridization.
AB  - Carbapenem-resistant Enterobacteriaceae have recently become an important cause
      of morbidity and mortality due to healthcare-associated infections. Most commonly
      used diagnostic methods are incompatible with fast and accurate directed therapy.
      We report here the direct identification of the blaOXA48 gene, which codes for
      the carbapenemase OXA-48, in lysate samples from Klebsiella pneumoniae. The
      method is PCR-free and label-free. It is based on the measurement of changes in
      the stiffness of DNA self-assembled monolayers anchored to microcantilevers that
      occur as a consequence of the hybridization. The stiffness of the DNA layer is
      measured through changes of the sensor resonance frequency upon hybridization and
      at varying relative humidity.

PMID- 29186954
TI  - Toward Highly Sensitive and Energy Efficient Ammonia Gas Detection with Modified
      Single-Walled Carbon Nanotubes at Room Temperature.
AB  - Fabrication and comparative analysis of the gas sensing devices based on
      individualized single-walled carbon nanotubes of four different types (pristine,
      boron doped, nitrogen doped, and semiconducting ones) for detection of low
      concentrations of ammonia is presented. The comparison of the detection
      performance of different devices, in terms of resistance change under exposure to
      ammonia at low concentrations combined with the detailed analysis of chemical
      bonding of dopant atoms to nanotube walls sheds light on the interaction of NH3
      with carbon nanotubes. Furthermore, chemoresistive measurements showed that the
      use of semiconducting nanotubes as conducting channels leads to the highest
      sensitivity of devices compared to the other materials. Electrical
      characterization and analysis of the structure of fabricated devices showed a
      close relation between amount and quality of the distribution of deposited
      nanotubes and their sensing properties. All measurements were performed at room
      temperature, and the power consumption of gas sensing devices was as low as 0.6
      MUW. Finally, the route toward an optimal fabrication of nanotube-based sensors
      for the reliable, energy-efficient sub-ppm ammonia detection is proposed, which
      matches the pave of advent of future applications.

PMID- 29186955
TI  - How Solid-Electrolyte Interphase Forms in Aqueous Electrolytes.
AB  - Solid-electrolyte interphase (SEI) is the key component that enables all advanced
      electrochemical devices, the best representative of which is Li-ion battery
      (LIB). It kinetically stabilizes electrolytes at potentials far beyond their
      thermodynamic stability limits, so that cell reactions could proceed reversibly.
      Its ad hoc chemistry and formation mechanism has been a topic under intensive
      investigation since the first commercialization of LIB 25 years ago.
      Traditionally SEI can only be formed in nonaqueous electrolytes. However, recent
      efforts successfully transplanted this concept into aqueous media, leading to
      significant expansion in the electrochemical stability window of aqueous
      electrolytes from 1.23 V to beyond 4.0 V. This not only made it possible to
      construct a series of high voltage/energy density aqueous LIBs with unprecedented
      safety, but also brought high flexibility and even "open configurations" that
      have been hitherto unavailable for any LIB chemistries. While this new class of
      aqueous electrolytes has been successfully demonstrated to support diversified
      battery chemistries, the chemistry and formation mechanism of the key component,
      an aqueous SEI, has remained virtually unknown. In this work, combining various
      spectroscopic, electrochemical and computational techniques, we rigorously
      examined this new interphase, and comprehensively characterized its chemical
      composition, microstructure and stability in battery environment. A dynamic
      picture obtained reveals how a dense and protective interphase forms on anode
      surface under competitive decompositions of salt anion, dissolved ambient gases
      and water molecule. By establishing basic laws governing the successful formation
      of an aqueous SEI, the in-depth understanding presented in this work will assist
      the efforts in tailor-designing better interphases that enable more energetic
      chemistries operating farther away from equilibria in aqueous media.

PMID- 29186956
TI  - How viruses infiltrate the central nervous system.
AB  - Central nervous system is protected by the blood-brain barrier, which represents
      a physical, metabolic and transport barrier and is considered to be a part of a
      highly dynamic system termed neurovascular unit. Several pathogens, among them
      viruses, are able to invade the brain. Traversal of viruses across the blood
      brain barrier is an essential step for the invasion of the central nervous system
      and can occur by different mechanisms - by paracellular, transcellular and/or by
      "Trojan horse" pathway. Penetration of viruses to brain can lead to the blood
      brain barrier dysfunction, including increased permeability, pleocytosis and
      encephalopathy. Viruses causing the central nervous system infections include
      human immunodeficiency virus type 1, rhabdovirus, different flaviviruses, mouse
      adenovirus type 1, herpes simplex virus, influenza virus, parainfluenza virus,
      reovirus, lymphocytic choriomeningitis virus, arbovirus, cytomegalovirus, mumps
      virus, parvovirus B19, measles virus, human T-cell leukemia virus, enterovirus,
      morbillivirus, bunyaviruses, togaviruses and others. In this review we summarized
      what is known about the routes of how some viruses enter the brain and how
      neurons and glial cells react to infection.

PMID- 29186957
TI  - The human pegivirus: A new name for an "ancient" virus. Can transfusion medicine
      come up with something new?
AB  - Human pegivirus (HPgV, formerly called GB virus C/hepatitis G virus) is a poorly
      understood RNA virus of the Flaviviridae family. The HPgV infection is common
      worldwide and the virus is likely transmitted by blood products. At this time, no
      causal association between HPgV and human diseases has been identified. While
      waiting for new findings to better understand the Pegivirus genus, the aim of our
      narrative review is to discuss the currently available information on HPgV
      focusing on its prevalence in blood donors and its potential threat to
      transfusion safety.

PMID- 29186958
TI  - Tick-borne viruses.
AB  - Tick-borne viruses (TBVs) belong to the largest biological group known as
      arboviruses with unique mode of transmission by blood-feeding arthropods (ticks,
      mosquitoes, sand flies, biting midges, etc.) to a susceptible vertebrate host.
      Taxonomically, it is a heterogenous group of vertebrate viruses found in several
      viral families. With only one exception, African swine fever virus, all TBVs have
      a RNA genome. To date, at least 160 tick-borne viruses are known, some of them
      pose a significant threat to human and animal health worldwide. Recently, a
      number of established TBVs has re-emerged and spread to new geographic locations
      due to the influence of anthropogenic activities and few available vaccines.
      Moreover, new emerging tick-borne diseases are constantly being reported. Major
      advances in molecular biotechnologies have led to discoveries of new TBVs and
      further genetic characterization of unclassified viruses resulting in changes in
      TBVs classification created by the International Committee for the Taxonomy of
      Viruses. Although TBVs spend over 95% of their life cycle within tick vectors and
      the role of ticks as vectors has been known for over 100 years, our knowledge
      about TBVs and molecular processes involved in the virus-tick interactions is
      scarce.

PMID- 29186959
TI  - Molecular characterization of two sugarcane streak mosaic virus isolates from
      Iran with emphasis on its population structure.
AB  - Sugarcane streak mosaic virus (SCSMV; the genus Poacevirus, the family
      Potyviridae) is an economically important causal agent of sugarcane mosaic
      disease in Asia. In this study, for the first time, we determined the complete
      genomic sequences of two Iranian SCSMV isolates, IR-Khuz6 and IR-Khuz57 from
      sugarcane. The sequences of both isolates were 9,782 nucleotides (nt) long,
      excluding the 3' poly(A) tail. Both of them contained a 5'-untranslated region
      (UTR) of 199 nt, an open reading frame of 9,393 nt encoding a polyprotein of
      3,130 amino acids (aa), and 3'-UTR of 190 nt. SCSMV-IR-Khuz6 and IR-Khuz57 genome
      nucleotide sequences were in 97.7% identical and shared identities of 81-92.4%
      with 10 other SCSMV isolates available in the GenBank. The highest identity was
      shared with the isolate PAK (NC_014037) from Pakistan. When separate genes were
      compared, most of the genes shared the highest identities with Pakistani isolate.
      Phylogenetic analysis of the complete genomic nucleotide and polyprotein amino
      acid sequences reveals that all SCSMV isolates clustered into two main groups.
      Both IR-Khuz6 and IR-Khuz57 clustered with isolates from Pakistan (PAK) and India
      (IND671) in group II but formed a separate subgroup. Population genetic analysis
      revealed greater between-group than within-group evolutionary divergence values,
      further supporting the results of the phylogenetic analysis. The results indicate
      that gene flow and selection pressure are important evolutionary factors shaping
      the genetic structure of SCSMV populations with implications for global exchange
      of sugarcane germplasm.

PMID- 29186960
TI  - Identification of novel E347Q and G362K amino acid substitutions in HN
      neutralization epitope and major antigenic difference in novel sub-genotype VIIj
      isolates.
AB  - Hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) plays a
      crucial role in induction of immune response against Newcastle disease infection.
      Mutation in residues 347 and 362 of HN linear antigenic site has been identified
      to be responsible for antigenic variations. Hence we studied antigenic difference
      between sub-genotype VIIj isolates and vaccine strains by the use of polyclonal
      serum against LaSota strain in hemagglutination inhibition test. Furthermore,
      epitope patterns of the isolates under study were analyzed and compared to HN
      sequences in GenBank. The results demonstrated that new Newcastle disease
      isolates (Mazandaran and Behshahr) had hemagglutination inhibition (HI) titer
      three and five, respectively while LaSota strain titer was eight. In addition,
      observation of sequences and epitope patterns revealed three unique amino acid
      substitutions (D144N, E347Q and G362K) in HN protein. E347Q and G362K mutations
      were located in neutralization antigenic site. Thus, we suggest that, these two
      novel amino acid substitutions in major linear epitope might be responsible for
      antigenic variation and decrease of HI activity.

PMID- 29186961
TI  - Relationship between PPP1R15A gene polymorphism (rs611251) and Epstein-Barr virus
      associated tumors.
AB  - Protein phosphatase 1, regulatory subunit 15A (PPP1R15A), also known as growth
      arrest and DNA damage-inducible protein GADD34, plays a vital role in promoting
      cell death and the unfolded protein response (UPR). In order to explore whether
      the SNP (rs611251) of PPP1R15A gene has a role in different types of Epstein-Barr
      virus (EBV) - associated tumors, we detected the PPP1R15A gene rs611251
      polymorphism in 195 cases of EBV positive tumors (93 lymphomas, 48 gastric
      carcinomas, 54 nasopharyngeal carcinomas), 208 cases of EBV-negative tumors (136
      gastric carcinoma, 19 nasopharyngeal carcinomas, 53 lymphomas) and 113 peripheral
      blood samples from healthy individuals. Compared with normal controls, the wild
      type TT and allele T of rs611251 showed higher frequency in gastric carcinoma
      (GCs), nasopharyngeal carcinomas (NPCs) and lymphomas. However, there was no
      significant difference between EBV-associated gastric (EBVaGC) and EBVnGC, EBV
      positive NPCs and EBV-negative NPCs, EBV-related lymphomas and EBV-negative
      lymphomas in rs611251 of PPP1R15A. In conclusion, the PPP1R15A rs611251
      polymorphism was significantly related to three kinds of tumors. Nevertheless,
      EBV has no obvious effect on PPP1R15A rs611251 polymorphism of NPC, GC and
      lymphoma. What's more, the genotype TT and allele T could be risk factors for
      NPC, GC and lymphoma. Our study explores the relationship between PPP1R15A gene
      polymorphism (rs611251) and Epstein-Barr virus-associated tumors for the first
      time. PPP1R15A gene SNP (rs611251) have association with multiple tumor types,
      which may provide some new clues to the detection and treatment of tumors.

PMID- 29186962
TI  - Genomic and phylogenetic evidence that Maize rough dwarf and Rice black-streaked
      dwarf fijiviruses should be classified as different geographic strains of a
      single species.
AB  - Maize rough dwarf disease (MRDD) has long been known as one of the most
      devastating viral diseases of maize worldwide and is caused by single or complex
      infection by four fijiviruses: Maize rough dwarf virus (MRDV) in Europe and the
      Middle East, Mal de Rio Cuarto virus (MRCV) in South America, rice black-streaked
      dwarf virus (RBSDV), and Southern rice black-streaked dwarf virus (SRBSDV or Rice
      black-streaked dwarf virus 2, RBSDV-2) in East Asia. These are currently
      classified as four distinct species in the genus Fijivirus, family Reoviridae,
      but their taxonomic status has been questioned. To help resolve this, the
      nucleotide sequences of the ten genomic segments of an Italian isolate of MRDV
      have been determined, providing the first complete genomic sequence of this
      virus. Its genome has 29144 nucleotides and is similar in organization to those
      of RBSDV, SRBSDV, and MRCV. The 13 ORFs always share highest identities (81.3
      97.2%) with the corresponding ORFs of RBSDV and phylogenetic analyses of the
      different genome segments and ORFs all confirm that MRDV clusters most closely
      with RBSDV and that MRCV and SRBSDV are slightly more distantly related. The
      results suggest that MRDV and RBSDV should be classified as different geographic
      strains of the same virus species and we suggest the name cereal black-streaked
      dwarf fijivirus (CBSDV) for consideration.

PMID- 29186963
TI  - Molecular epidemiology and genetic diversity of duck hepatitis A virus type 3 in
      Shandong province of China, 2012-2014.
AB  - The infections with duck hepatitis A virus type 3 (DHAV-3) become common in
      eastern Asia. To better understand the molecular evolution and genetic variation
      of DHAV-3, a total of 482 dead Cherry Valley duckling liver samples collected
      from Shandong province of China during 2012-2014 were tested, and the complete P1
      coding sequences of 18 DHAV-3 strains were analyzed. The detection rate of DHAV-3
      was 64.5% (311/482) in clinical liver samples and 73.0% (92/126) in duckling
      flocks. The P1 genes of the 18 DHAV-3 isolates shared 91.9%-99.0% nucleotide
      similarity and 95.2%-100% amino acid similarity with those of the other 26
      reference strains. Based on the P1 and VP1 gene sequences, phylogenetic analysis
      results indicated that the genotyping of DHAV-3 strains presented a distinct
      geographical distribution. Except B63 strain, all Chinese strains isolated from
      different host species (duck or goose) at different time were classed into the CH
      genotype. All Korean and Vietnamese strains belonged to the KV genotype, and all
      the Korean strains were clustered into KV1 subgenotype, while B63 strain and the
      Vietnamese strains from different host species (duck or goose) were clustered
      into KV2 subgenotype. Ten variable amino acid residues were highly conserved
      within genotypes or subgenotypes in the VP0, VP3 and VP1, respectively, which
      were possibly the geographic molecular markers of DHAV-3. To the best of our
      knowledge, this is the first study about the genetic variation of the P1 gene of
      different DHAV-3 strains, which will be helpful for understanding of the
      molecular epidemiology of DHAV-3.

PMID- 29186964
TI  - Yeast two-hybrid and pull-down assays propose an interaction between P50 of apple
      chlorotic leaf spot virus and PR-10 of Malus sylvestris cv. R12740-7A.
AB  - Apple chlorotic leaf spot virus (ACLSV) movement protein (P50) is involved in
      cell-to-cell transport and influences the long-distance spread of silencing
      activity. Previously, we obtained 69 P50-interacting proteins from Malus
      sylvestris cv. R12740-7A and using bioinformatics analyzed their biological
      functions. In this study, we used the GAL4-based two-hybrid yeast system and His
      pull-down assays to confirm an interaction between PR-10 of M. sylvestris cv.
      R12740-7A and ACLSV P50. Our results provide a theoretical basis for further
      research on the biological function of PR-10 in ACLSV infection and the
      interacting mechanism between host and virus.

PMID- 29186965
TI  - Genome sequence of a distinct watermelon mosaic virus identified from ginseng
      (Panax ginseng) transcriptome.
AB  - Watermelon mosaic virus (WMV) is a member of the genus Potyvirus, which is the
      largest genus of plant viruses. WMV is a significant pathogen of crop plants,
      including Cucurbitaceae species. A WMV strain, designated as WMV-Pg, was
      identified in transcriptome data collected from ginseng (Panax ginseng) root. WMV
      Pg showed 84% nucleotide sequence identity and 91% amino acid sequence identity
      with its closest related virus, WMV-Fr. A phylogenetic analysis of WMV-Pg with
      other WMVs and soybean mosaic viruses (SMVs) indicated that WMV-Pg is a distinct
      subtype of the WMV/SMV group of the genus Potyvirus in the family Potyviridae.

PMID- 29186966
TI  - First report of bovine herpesvirus 1 isolation from bull semen samples in China.
AB  - Bovine herpesvirus 1 (BoHV-1) infection causes substantial economic losses to the
      cattle industry worldwide. So far, the isolation of BoHV-1 field virus has not
      been reported in China. Here, for the first time we report that two isolates of
      BoHV-1 designated as NJ16-1 and NJ16-2 were obtained from semen samples from
      breeding bulls in China. Typical cytopathic effect in MDBK cells, detection of
      viral protein VP16 in western blot analysis, PCR detection of BoHV-1 gB gene
      proved BoHV-1 infection and subsequent nucleotide sequence analysis showed a 99%
      identity with BoHV-1 Cooper strain. These results suggest that these isolated
      viruses are BoHV-1.

PMID- 29186967
TI  - Calcium signaling involved in bovine herpesvirus 1 replication in MDBK cells.
AB  - Calcium is one of the most prominent second messengers in eukaryotic cells. The
      involvement of calcium signaling in bovine herpesvirus 1 (BoHV-1) replication was
      not yet reported. In this study, we revealed that the L-type Ca2+ calcium channel
      blocker, Verapamil and store-operated calcium channel blocker, 2-aminoethyl
      diphenylborinate (2-APB) inhibited BoHV-1 replication in MDBK cells at the post
      entry stages, and the Na+/Ca2+ exchanger inhibitor, N-arachidonoyl glycine
      exchanger (NAGly) interfered with the viral entry process. NAGly also effected
      the phosphorylation of PLCgamma-1 at Ser1248, which corroborated our previous
      findings, that PLCgamma-1 is important for BoHV-1 entry. Collectively, these
      results suggest that diverse calcium channels are employed by BoHV-1 for
      efficient replication.

PMID- 29186968
TI  - Tracking the potyviral P1 protein in Nicotiana benthamiana plants during plum pox
      virus infection.
AB  - The P1 protein is derived from the N terminus of potyvirus-coded polyprotein. In
      addition to the proteolytic activity essential for its maturation, it probably
      participates in suppression of host defense and/or in virus replication. Clear
      validation of the P1 in vivo function(s), however, is not yet available. We
      applied an infectious cDNA clone of plum pox virus (PPV), where the P1 was N
      fused with a hexahistidine tag, to trace this protein in Nicotiana benthamiana
      plants during the PPV infection. Immunoblot analysis with the anti-his antibody
      showed a diffuse band corresponding to the molecular weight about 70-80 kDa
      (about twice larger than expected) in the root samples from early stage of
      infection. This signal culminated on the sixth day post inoculation, later it
      rapidly disappeared. Sample denaturation by boiling in SDS before centrifugal
      clarification was essential, indicating strong affinity of P1-his to some plant
      compound sedimenting with the tissue and cell debris.

PMID- 29186969
TI  - Neuronal and astrocytic involvement in striped dolphins (Stenella coeruleoalba)
      with morbilliviral encephalitis.
AB  - Dolphin morbillivirus (DMV), a highly pathogenic agent, may cause peculiar,
      "brain-only" forms of infection (BOFDI), in which viral antigen and/or genome is
      found exclusively in the brain from striped dolphins (Stenella coeruleoalba).
      These BOFDIs show morphopathological similarities with subacute sclerosing
      panencephalitis and old dog encephalitis (ODE) in measles virus-infected patients
      and in canine distemper virus-infected dogs, respectively. The brain tissue from
      3 BOFDI-affected striped dolphins was investigated by means of double labelling
      indirect immunofluorescence (DL-IIF) and ultrastructurally, in order to
      characterize the DMV-targeted neuronal and non-neuronal cell populations, along
      with the associated submicroscopic findings. Viral colonization of calbindin
      immunoreactive (IR) and nitric oxide synthase-IR neurons was detected in the
      cerebral parenchyma from the 3 DMV-infected dolphins under study, associated with
      nuclear (chromatin) and cytoplasmic (mitochondrial) ultrastructural changes.
      Furthermore, a limited viral targeting of brain astrocytes was found in these
      animals, all of which exhibited a prominent astrogliosis/astrocytosis. To the
      best of our knowledge, those herein reported should be the first submicroscopic
      pathology and neuropathogenetic data about BOFDI in striped dolphins. In this
      respect, the marked astrogliosis/astrocytosis and the low viral colonization of
      brain astrocytes in the 3 DMV-infected dolphins under investigation are of
      interest from the comparative pathology and viral neuropathogenesis standpoints,
      when compared with ODE-affected dogs, in whose brain a non-cytolytic, astrocyte
      to-astrocyte infectious spread has been recently documented. Further studies
      aimed at characterizing the complex DMV-host interactions in BOFDI-affected
      striped dolphins are needed.

PMID- 29186970
TI  - First report of Hosta virus X infecting hosta plants in Ukraine.
AB  - In September 2011, the leaf samples of hosta cultivar 'Sum and substance' were
      collected from the collection of Gryshko' National Botanical Garden in Kyiv. The
      leaves showed dark green streaking and puckering along the leaf veins.
      Transmission electron microscopy revealed the presence of filamentous viral
      particles 13 nm in diameter and 470-580 nm in length. Reverse transcription PCR
      (RT-PCR) analysis confirmed the presence of Hosta virus X (HVX). The sequencing
      of the complete genome revealed 99% identity to HVX-37 and 97.5% identity to HVX
      Kr. Notably, ORF4 initiation codon presented a non-conventional start codon (UUG)
      like it was previously identified in HVX-37.

PMID- 29186971
TI  - Reactive Oxygen Species and Oncoprotein Signaling-A Dangerous Liaison.
AB  - SIGNIFICANCE: There is evidence to implicate reactive oxygen species (ROS) in
      tumorigenesis and its progression. This has been associated with the interplay
      between ROS and oncoproteins, resulting in enhanced cellular proliferation and
      survival. Recent Advances: To date, studies have investigated specific
      contributions of the crosstalk between ROS and signaling networks in cancer
      initiation and progression. These investigations have challenged the established
      dogma of ROS as agents of cell death by demonstrating a secondary function that
      fuels cell proliferation and survival. Studies have thus identified
      (onco)proteins (Bcl-2, STAT3/5, RAS, Rac1, and Myc) in manipulating ROS level as
      well as exploiting an altered redox environment to create a milieu conducive for
      cancer formation and progression. CRITICAL ISSUES: Despite these advances, drug
      resistance and its association with an altered redox metabolism continue to pose
      a challenge at the mechanistic and clinical levels. Therefore, identifying
      specific signatures, altered protein expressions, and modifications as well as
      protein-protein interplay/function could not only enhance our understanding of
      the redox networks during cancer initiation and progression but will also provide
      novel targets for designing specific therapeutic strategies. FUTURE DIRECTIONS:
      Not only a heightened realization is required to unravel various gene/protein
      networks associated with cancer formation and progression, particularly from the
      redox standpoint, but there is also a need for developing more sensitive tools
      for assessing cancer redox metabolism in clinical settings. This review attempts
      to summarize our current knowledge of the crosstalk between oncoproteins and ROS
      in promoting cancer cell survival and proliferation and treatment strategies
      employed against these oncoproteins. Antioxid. Redox Signal.

PMID- 29186972
TI  - Sarcopenia in chronic obstructive pulmonary disease: A study of prevalence and
      associated factors in the Southeast Asian population.
AB  - Chronic obstructive pulmonary disease (COPD) has been described as a systemic
      disease. Sarcopenia is one of the systemic effects that is related to several
      adverse outcomes. The objectives of this study were to estimate the prevalence of
      sarcopenia and to determine the factors associated with sarcopenia in COPD
      patients in Southeast Asia. This was a cross-sectional study of COPD patients who
      attended a COPD clinic from May 2015 to December 2016. Baseline characteristics
      were collected and dual-energy X-ray absorptiometry was used to measure skeletal
      muscle mass. Handgrip strength was used to assess muscle strength, and as a
      measurement of physical performance, the 6-min walk distance was used. One
      hundred and twenty-one participants were recruited. Most of them were men
      (92.6%). Prevalence of sarcopenia was 24% (29 cases). Independent factors
      associated with sarcopenia were age >= 75 years (adjusted odds ratio (AOR) 13.3,
      severity of COPD (AOR 19.2 and 13.4 for moderate and severe COPD), Modified
      Medical Research Council (MMRC) scale (AOD 1.9), and obesity (AOR 0.04).
      Sarcopenia affects about one-quarter of COPD patients. Age, severity of COPD,
      MMRC scale, and BMI status were the factors associated with sarcopenia.

PMID- 29186974
TI  - [Neuropsychological Profile and Working Memory in Bipolar Disorder].

PMID- 29186975
TI  - Mammalian Sulfur Amino Acid Metabolism: A Nexus Between Redox Regulation,
      Nutrition, Epigenetics, and Detoxification.
AB  - SIGNIFICANCE: Transsulfuration allows conversion of methionine into cysteine
      using homocysteine (Hcy) as an intermediate. This pathway produces S
      adenosylmethionine (AdoMet), a key metabolite for cell function, and provides 50%
      of the cysteine needed for hepatic glutathione synthesis. The route requires the
      intake of essential nutrients (e.g., methionine and vitamins) and is regulated by
      their availability. Transsulfuration presents multiple interconnections with
      epigenetics, adenosine triphosphate (ATP), and glutathione synthesis, polyol and
      pentose phosphate pathways, and detoxification that rely mostly in the exchange
      of substrates or products. Major hepatic diseases, rare diseases, and
      sensorineural disorders, among others that concur with oxidative stress, present
      impaired transsulfuration. Recent Advances: In contrast to the classical view, a
      nuclear branch of the pathway, potentiated under oxidative stress, is emerging.
      Several transsulfuration proteins regulate gene expression, suggesting
      moonlighting activities. In addition, abnormalities in Hcy metabolism link
      nutrition and hearing loss. CRITICAL ISSUES: Knowledge about the crossregulation
      between pathways is mostly limited to the hepatic availability/removal of
      substrates and inhibitors. However, advances regarding protein-protein
      interactions involving oncogenes, identification of several post-translational
      modifications (PTMs), and putative moonlighting activities expand the potential
      impact of transsulfuration beyond methylations and Hcy. FUTURE DIRECTIONS:
      Increasing the knowledge on transsulfuration outside the liver, understanding the
      protein-protein interaction networks involving these enzymes, the functional role
      of their PTMs, or the mechanisms controlling their nucleocytoplasmic shuttling
      may provide further insights into the pathophysiological implications of this
      pathway, allowing design of new therapeutic interventions. Antioxid. Redox
      Signal. 29, 408-452.

PMID- 29186973
TI  - Exercise for Cognitive Symptoms in Depression: A Systematic Review of
      Interventional Studies.
AB  - OBJECTIVE: To explore the effect of exercise on cognition in depression as well
      as the impact of potential moderators and intervention type. METHOD: Controlled
      and uncontrolled interventional studies that described an exercise intervention
      and cognitive outcomes in participants with major depressive disorder (MDD) were
      included following a search of Pubmed, Ovid Medline, PsycInfo and Embase from
      inception to January 2017. Meta-analyses were conducted to calculate Hedges' g
      using a random-effects model. Meta-regression explored the relationships among
      age, baseline cognition, frequency and duration of exercise, and cognitive
      outcomes. Subgroup analyses were also conducted according to type and intensity
      of exercise interventions. RESULTS: Of 12 controlled studies and 3 uncontrolled
      studies that met inclusion criteria, 9 (642 patients) were included in the meta
      analysis. No significant effect of exercise was found on global cognition
      (Hedges' g = 0.08, P = 0.33, I2 = 0%) or on individual cognitive domains. Meta
      regression analyses failed to find significant relationships among participant
      age, baseline cognition, number of exercise sessions per wk, duration of exercise
      per wk, total duration of exercise during the intervention, or improvement in
      global cognition. Interventions combining physical with cognitive activity
      significantly improved global cognition ( P = 0.048), whereas low-intensity
      interventions were also positive ( P = 0.048). CONCLUSIONS: No impact of physical
      exercise was found on cognition in MDD overall. However, we found that
      interventions combining physical and cognitive activities had a positive impact,
      and that lower-intensity interventions, where adherence was improved, also
      impacted positively. There remains a lack of high-quality data in this
      population.

PMID- 29186976
TI  - Effectiveness of Heated Sterile Water vs ResoClear(r) for Prevention of
      Laparoscopic Lens Fogging in a Randomized Comparative Trial.
AB  - BACKGROUND: Laparoscopic surgery may be complicated by visual disturbances,
      including lens fogging. Several techniques have been developed to prevent
      laparoscopic lens fogging (LLF). We aim to compare the effectiveness of two
      commonly available techniques in prevention of LLF: heated sterile water in a
      thermos flask and ResoClear(r) impregnation wipes. MATERIALS AND METHODS: In this
      single-center prospective randomized study, 50 patients underwent an elective
      laparoscopic donor nephrectomy and were allocated to either heated sterile water
      or ResoClear(r) impregnation wipes as the antifogging method. The primary outcome
      was the number of fogging events during the first 30 minutes of the operation,
      whereas secondary outcomes were operating time, number of cleaning events because
      of other causes, cost differences, and assessment of predicting factors for
      fogging events. RESULTS: In 50 patients, the outcomes were analyzed. The number
      of fogging events was significantly lower when using heated sterile water (median
      = 0, interquartile range [IQR]: 0-0) compared to ResoClear(r) (median 1.0, IQR:
      0.5-3.0), p < 0.001. There were no significant differences in operating time,
      number of cleaning events because of other causes, and costs. No predictors of
      fogging events were found. CONCLUSION: The use of heated sterile water leads to
      significantly less fogging events than the use of ResoClear(r) impregnation
      wipes, resulting in an improved continuity of the surgery without differences in
      operating time and costs.

PMID- 29186977
TI  - Ictal Rhythmic Alpha Sinusoidal Waves in 3 Cases of Anti-NMDAR Encephalitis.
AB  - Previous studies have shown that extreme delta brush and high beta/delta power
      ratio on electroencephalogram are suggestive of anti- N-methyl-d-aspartate
      receptor (anti-NMDAR) encephalitis. Here we report 3 anti-NMDAR encephalitis
      patients with ictal rhythmic alpha sinusoidal waves in temporal regions, which
      suggested electrographic seizures in anti-NMDAR encephalitis and indicated
      potential for seizure occurrence in the future. Rhythmic alpha sinusoidal waves
      may be an electrographic feature and helpful in distinguishing anti-NMDAR
      encephalitis. In addition, extreme delta brush was also observed at 47-50 days
      after morbidity in 2 of 3 patients.

PMID- 29186978
TI  - Association of liver cirrhosis severity with type 2 diabetes mellitus in
      hepatocellular carcinoma.
AB  - Type 2 diabetes mellitus (T2DM) is a major risk factor associated with
      hepatocellular carcinoma (HCC). However, the association of T2DM with liver
      cirrhosis and therapy response in HCC patients is not clear. Hence, in this
      study, we have evaluated the influence of T2DM on liver cirrhosis severity of HCC
      and sorafenib response. HCC patients were divided in two groups: T2DM (n = 20)
      and non-T2DM (nT2DM; n = 50). We found significantly higher number of patients in
      T2DM group had decompensated liver disease with Child-Turcotte-Pugh score >= 7.
      Additionally, 71.4% patients were observed to be sorafenib sensitive in T2DM
      group which was significantly higher as compared to 30% in nT2DM group. This
      study has highlighted the predisposition of HCC patients with T2DM toward more
      severe liver disease who were found to be better respondents of sorafenib. Impact
      statement We have explored the association of type 2 diabetes mellitus (T2DM) on
      liver cirrhosis severity along with response toward sorafenib in hepatocellular
      carcinoma (HCC). Most HCC patients exhibit prior history of liver cirrhosis that
      results following long span of chronic liver disease. T2DM constitutes as an
      important risk factor for HCC development which is known to elevate its
      incidence. Further, sorafenib is the FDA approved therapy for HCC whose
      therapeutic outcome is not investigated in HCC patients with T2DM till date. This
      observation-based study has unveiled a positive association between T2DM and
      severity of liver cirrhosis as well as sorafenib response in HCC as examined in a
      clinical setting.

PMID- 29186979
TI  - The need for immune biomarkers for treatment prognosis and response in
      genitourinary malignancies.
AB  - Immune biomarkers encompass a wide range of blood-borne and cell-associated
      molecules whose detection or expression may change in response to an immune
      therapy. These immune therapies encompass a range of platforms including
      autologous cellular products, in other words, dendritic cells, prime boost DNA
      vaccines, chimeric antigen receptor (CAR) T cells and checkpoint inhibitors. The
      response to checkpoint inhibitors by a particular cancer may not be necessarily
      associated with a change in a particular immune biomarker; other immune
      biomarkers are needed to assess their association with treatment response or a
      change in the biology that can impact on the immunologic milieu. How these
      potential biomarkers can be incorporated into clinical trial design, and their
      role in interrogating the immunologic milieu will be discussed.

PMID- 29186980
TI  - Overexpressed miR-128a enhances chemoradiotherapy to laryngeal cancer cells and
      its correlation with BMI1.
AB  - AIM: To clarify the function of miR-128a on radiotherapy and chemotherapy
      resistance in laryngeal cancer and explore the possible mechanism. MATERIALS &
      METHODS: Hep-2 and AMC-HN-8 cell lines were cultured. MiR-128a was upregulated
      utilizing lentiviral transfection. Through radiotherapy and chemotherapy assays,
      the function of miR-128a on chemoradiotherapy was evaluated. The correlation of
      miR-128a with BMI1 was identified by performing real-time PCR. RESULTS: The hsa
      miR128a cell line was established. The chemotherapy assay revealed that an
      overexpression of miR-128a decreases the inhibition to chemotherapy. The
      radiotherapy assay showed that miR-128a promotes the radiotherapy sensitivity.
      The expression of BMI1 decreased with overexpression of miR-128a. CONCLUSION: miR
      128a confers chemoradiotherapy sensitivity of laryngeal cancer cells and
      targeting BMI1 gene is a possible mechanism of the effect.

PMID- 29186981
TI  - Oxidative Stress Induces an Interactive Decline in Wnt and Nrf2 Signaling in
      Degenerating Retinal Pigment Epithelium.
AB  - AIMS: Cells have evolved a highly sophisticated web of cytoprotective systems to
      neutralize unwanted oxidative stress, but are challenged by unique modern day
      stresses such as cigarette smoking and ingestion of a high-fat diet (HFD). Age
      related disease, such as age-related macular degeneration (AMD), the most common
      cause of blindness among the elderly in Western societies, develops in part, when
      oxidative stress overwhelms cytoprotective systems to injure tissue. Since most
      studies focus on the protection by a single protective system, the aim of this
      study was to investigate the impact of more than one cytoprotective system
      against oxidative stress. RESULTS: Wingless (Wnt) and nuclear factor-erythroid 2
      related factor 2 (Nrf2), two fundamental signaling systems that are vital to cell
      survival, decline after mice are exposed to chronic cigarette smoke and HFD, two
      established AMD risk factors, in a bidirectional feedback loop through
      phosphorylated glycogen synthase kinase 3 beta. Decreased Wnt and Nrf2 signaling
      leads to retinal pigment epithelial dysfunction and apoptosis, and a phenotype
      that is strikingly similar to geographic atrophy (GA), an advanced form of AMD
      with no effective treatment. INNOVATION: This study is the first to show that
      chronic oxidative stress from common modern day environmental exposures reduces
      two fundamental and vital cytoprotective networks in a bidirectional feedback
      loop, and their decline leads to advanced disease phenotype. CONCLUSION: Our data
      offer new insights into how combined modern oxidative stresses of cigarette
      smoking and HFD contribute to GA through an interactive decline in Wnt and Nrf2
      signaling. Antioxid. Redox Signal. 29, 389-407.

PMID- 29186983
TI  - The Accuracy of the Edmonton Symptom Assessment System for the Assessment of
      Depression in Patients With Cancer: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Depression is a common health problem among patients with cancer. The
      Edmonton Symptom Assessment System (ESAS) is one of many tools that have been
      used to evaluate depression in these patients. Nevertheless, the diagnostic
      performance and the appropriate cutoff point of the ESAS for the assessment of
      depression in these patients have varied in the studies. PURPOSE: To determine
      the diagnostic accuracy and the optimal cutoff point for the ESAS for the
      assessment of depression in patients with cancer. DATA SOURCES: PubMed, Scopus,
      CINAHL, and Cochrane library databases from inception to September 18, 2016.
      STUDY SELECTION: Paired reviewers independently screened abstracts and full-text
      articles for all cross-sectional studies published in English and compared these
      with the ESAS in the depression (ESAS-D) subscale with reference to standard
      tests for the assessment of depression. DATA EXTRACTION: Two reviewers serially
      abstracted the data and independently assessed the risk of bias by using the
      Quality Assessment of Diagnostic Accuracy Studies 2. DATA SYNTHESIS: A total of 6
      studies were eligible for review. Our meta-analysis showed the optimal cutoff
      point of the ESAS-D >= 4, with pooled sensitivity and specificity at 53% (95%
      confidence interval [CI]: 38%-67%) and 90% (95% CI: 82%-94%), respectively. The
      positive likelihood ratio and diagnostic odds ratio of the ESAS-D >= 4 were 5.2
      (95% CI: 3.1-8.6) and 10 (95% CI: 5-19). There was a high degree of heterogeneity
      between the studies ( P value <.001, I2 = 96%). CONCLUSION: We suggest that an
      ESAS-D >= 4 could be used to detect possible cases of depression in patients with
      cancer. Registration: Our study protocol was registered with the International
      Prospective Register of Systematic Reviews on October 4, 2016, and was last
      updated on January 11, 2017 (registration number CRD42016048288).

PMID- 29186982
TI  - A Randomized Controlled Trial of Strategies to Improve Family Members'
      Preparedness for Surrogate Decision-Making.
AB  - OBJECTIVE: To evaluate 2 strategies for preparing family members for surrogate
      decision-making. DESIGN: A 2 * 2 factorial, randomized controlled trial testing
      whether: (1) comprehensive online advance care planning (ACP) is superior to
      basic ACP, and (2) having patients engage in ACP together with family members is
      superior to ACP done by patients alone. SETTING: Tertiary care centers in
      Hershey, Pennsylvania, and Boston, Massachusetts. PARTICIPANTS: Dyads of patients
      with advanced, severe illness (mean age 64; 46% female; 72% white) and family
      members who would be their surrogate decision-makers (mean age 56; 75% female;
      75% white). INTERVENTIONS: Basic ACP: state-approved online advance directive
      plus brochure. Making Your Wishes Known (MYWK): Comprehensive ACP decision aid
      including education and values clarification. MEASUREMENTS: Pre-post changes in
      family member self-efficacy (100-point scale) and postintervention concordance
      between patients and family members using clinical vignettes. RESULTS: A total
      285 dyads enrolled; 267 patients and 267 family members completed measures.
      Baseline self-efficacy in both MYWK and basic ACP groups was high (90.2 and 90.1,
      respectively), and increased postintervention to 92.1 for MYWK ( P = .13) and
      93.3 for basic ACP ( P = .004), with no between-group difference. Baseline self
      efficacy in alone and together groups was also high (90.2 and 90.1,
      respectively), and increased to 92.6 for alone ( P = .03) and 92.8 for together (
      P = .03), with no between-group difference. Overall adjusted concordance was
      higher in MYWK compared to basic ACP (85.2% vs 79.7%; P = .032), with no between
      group difference. CONCLUSION: The disconnect between confidence and performance
      raises questions about how to prepare family members to be surrogate decision
      makers.

PMID- 29186985
TI  - Psychometric Properties of the Perceived Wellness Culture and Environment Support
      Scale.
AB  - OBJECTIVE: This study reports on the psychometric properties of the 11-item
      Perceived Wellness Culture and Environment Support Scale (PWCESS) and its
      relationship with employee healthy lifestyle beliefs and behaviors. METHODS:
      Faculty and staff (N = 3959) at a large public university in the United States
      mid-west completed the PWCESS along with healthy lifestyle beliefs and behaviors
      scales. Data were randomly split into 2 halves to explore the PWCESS' validity
      and reliability and the second half to confirm findings. RESULTS: Principal
      components analysis indicated a unidimensional construct. The PWCESS was
      positively related to healthy lifestyle beliefs and behaviors supporting the
      scale's validity. Confirmatory factor analysis supported the unidimensional
      construct (Cronbach's alpha = .92). CONCLUSION: Strong evidence supports the
      validity and reliability of the PWCESS. Future use of this scale could guide
      workplace intervention strategies to improve organizational wellness culture and
      employee health outcomes.

PMID- 29186984
TI  - Healthy Immigrant Families: Randomized Controlled Trial of a Family-Based
      Nutrition and Physical Activity Intervention.
AB  - PURPOSE: To evaluate a healthy eating and physical activity intervention for
      immigrant families, derived through community-based participatory research.
      DESIGN: The Healthy Immigrant Families study was a randomized controlled trial
      with delayed intervention control group, with families as the randomization unit.
      SETTING: US Midwest city. PARTICIPANTS: Participants were recruited by community
      partners from Hispanic, Somali, and Sudanese immigrant communities. INTERVENTION:
      Family health promoters from participating communities delivered 6 healthy eating
      modules, 4 physical activity modules, and 2 modules synthesizing information in
      12 home visits (60-90 minutes) within the first 6 months. Up to 12 follow-up
      phone calls to each participant occurred within the second 6 months. MEASURES:
      Primary measures were dietary quality measured with weekday 24-hour recall and
      reported as Healthy Eating Index score (0-100) and physical activity measured
      with accelerometers (14 wear days) at baseline, 6, 12, and 24 months. RESULTS: In
      total, 151 persons (81 adolescents and 70 adults; 44 families) were randomly
      assigned. At 12 months, significant improvement occurred in Healthy Eating Index
      scores for adults in the intervention group compared with controls (change, +8.6
      vs -4.4; P < .01) and persisted at 24 months (+7.4 from baseline; P < .01). No
      differences were observed for adolescents and no significant differences occurred
      between groups for physical activity. CONCLUSION: This intervention produced
      sustained dietary quality improvement among adults but not among adolescents.
      Program outcomes are relevant to communities working to decrease cardiovascular
      risk among immigrant populations.

PMID- 29186986
TI  - Steroid-induced mental disorders in cancer patients: a systematic review.
AB  - Corticosteroids are a central part of many cancer treatment regimens.
      Neuropsychiatric toxicity has complicated their use, including an association
      with a spectrum of symptoms, from insomnia, cognitive impairment and mood
      symptoms, to severe mental disorders, including mania, psychosis and severe
      depression. Although steroid-induced mental disorders were first reported in
      medicine more than 60 years ago, there is a dearth of evidence available to date
      on optimal treatment and prevention to guide cancer clinicians. We completed a
      systematic review of the current evidence for therapeutic and prophylactic
      interventions of steroid-induced mental disorders in cancer. We searched Medline,
      Embase and PsycINFO and selected studies related to steroid-induced mental
      disorder. The studies found were limited to case series and case reports only.

PMID- 29186987
TI  - Perurethral transvesical route for oocytes retrieval: an old technique for a new
      indication in oncofertility.
AB  - : We aimed to evaluate the safety and efficiency of the peruretheral transvesical
      oocyte retrieval in oncofertility. We conducted a retrospective comparative study
      in our assisted reproductive technologies center. STUDY GROUP: 28 pubertal young
      women affected by malignancies, referred for fertility preservation and refusing
      transvaginal (TV) procedure. CONTROL GROUP: 28 infertile patients, aged less than
      25 years, who have undergone in vitro fertilization with TV oocyte retrieval. The
      ovarian stimulation was significantly longer on the study group. There was no
      difference between the two groups regarding mean number of collected metaphase II
      oocytes. One patient of the study group had a transient dysuria. These
      preliminary data suggest that, in oncofertility, peruretheral transvesical oocyte
      retrieval is an alternative when the TV route is refused or not feasible.

PMID- 29186988
TI  - Interchangeability of biosimilar and biological reference product: updated
      regulatory positions and pre- and post-marketing evidence.
AB  - INTRODUCTION: Since 2006, biosimilars have been available in several countries
      worldwide, thus allowing for potential savings in pharmaceutical expenditure.
      However, there have been numerous debates about the interchangeability of
      biosimilars and reference products based on concerns of immunogenicity by
      switching between biological products, which may cause lack of effect and
      toxicity. Areas covered: The authors provide the reader with an overview of the
      different positions of regulatory authorities on the interchangeability and
      automatic substitution of biosimilars and reference products. Presently, the FDA
      allows automatic substitution without prescriber intervention if the biosimilar
      is interchangeable with reference products, while the European Medicines Agency
      delegate to each single EU member state. Expert opinion: Different approaches in
      defining interchangeability and automatic substitution call for harmonization to
      increase confidence of healthcare professionals and patients about the clinical
      impact of switching. Networks of electronic healthcare records and administrative
      databases, potentially linkable to clinical charts and registries may rapidly
      assess frequency and benefit-risk profile of different switching patterns in
      routine care at different levels, thus integrating and strengthening pre
      marketing evidence.

PMID- 29186989
TI  - Treatment of Distal Ureteral Calculi Using Extracorporeal Physical Vibrational
      Lithecbole Combined with Tamsulosin: A New Option to Speed Up Obstruction Relief.
AB  - INTRODUCTION: The obstruction of the urinary tract by calculi at the narrowest
      anatomical areas leads to impaired drainage and severe pain. The aim of this
      study was to evaluate a new technology, extracorporeal physical vibrational
      lithecbole (EPVL) combined with tamsulosin, as a treatment for distal ureteral
      calculi (DUC). MATERIALS AND METHODS: Between July 2013 and July 2014, 672
      patients diagnosed with DUC were randomly divided into three groups; a group
      receiving EPVL plus 0.4 mg oral tamsulosin daily (PO qd) (experimental group, n =
      236), a group receiving 0.4 mg tamsulosin PO qd (n = 222), and a group receiving
      EPVL only (n = 214) (control groups). RESULTS: There were no significant
      differences in general characteristics between the three groups. Stone diameters
      ranged from 0.32 to 1 cm. In the EPVL plus tamsulosin group, 60.1% of patients
      showed detectable fragment expulsion at 48 hours, and 91.1% were stone free at 7
      days. Compared with the two control groups, these rates were significantly higher
      (EPVL group was 0% and 50.5% and medical expulsive therapy group was 0% and
      50.0%, p < 0.05). The stone-free rates were similar in the three groups 2 weeks
      later (94.5%, 93.6%, and 93.5%; p > 0.05). Patients in the EPVL plus tamsulosin
      group achieved similar stone-free rates compared with the other two groups, but
      the speed of the stone expulsion was quicker for both sexes and all age groups
      (about a week; p < 0.05). CONCLUSION: This indicates that EPVL plus tamsulosin
      could be used as an effective, but faster treatment option for patients with DUC,
      alleviating the symptoms of DUC in a shorter period of time.

PMID- 29186990
TI  - Nanomedicine approaches for sirolimus delivery: a review of pharmaceutical
      properties and preclinical studies.
AB  - Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with
      immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis
      and anti-inflammatory properties. However, its clinical application is often
      hampered by poor aqueous solubility, first-pass metabolism, transport by p
      glycoprotein efflux pump, limited oral bioavailability and nonspecific
      distribution in off-target sites. Recently, various formulation strategies have
      emerged to overcome these limitations. Among these, pharmaceutical nanotechnology
      with numerous advantages has great potential for sirolimus delivery. Up to now,
      the only nanoparticle based FDA approved formulation in the market is Rapamune(r)
      tablet which is composed of drug nanocrystals. This review focuses on recent
      studies that have been investigated various nanostructured carriers such as
      liposomes, micelles, polymeric nanoparticles, nanocrystals, magnetic
      nanoparticles, albumin nanoparticles, solid dispersion nanoparticles and niosomes
      for sirolimus delivery (in organ transplantation, cancer, vascular restenosis,
      etc.).

PMID- 29186991
TI  - Two new labdane-type diterpenoids cinnamate from Croton decalvatus Esser.
AB  - Two new labdane diterpene derivatives, crotondecalvatin A (1) and
      crotondecalvatin B (2) were obtained from the leaves and twigs of Croton
      decalvatus. The structures of compounds were established on the basis of
      extensive spectroscopic data.

PMID- 29186992
TI  - Evaluation of the Southern Harm Reduction Coalition for HIV Prevention: Advocacy
      Accomplishments.
AB  - BACKGROUND: HIV/AIDS rates are higher in the Southern United States compared to
      other regions of the country. Reasons for disparities include poverty, health
      care access, and racism. People who inject drugs (PWID) account for 8% of
      HIV/AIDS incidence rates. Harm reduction can connect PWID to needed resources.
      AIDS United Southern REACH grantees developed the Southern Harm Reduction
      Coalition (SHRC) as a means to decrease HIV/AIDS and viral hepatitis rates,
      criminalization of drug users and sex workers, and drug overdose. METHOD:
      Investigators used an intrinsic case study design to examine the context of harm
      reduction in the Southern United States, successful strategies, and outcomes.
      Data collection included key informant interviews and coalition documents. The
      community coalition action theory was used to examine the data. RESULTS: The SHRC
      initiated regional conferences and customized trainings. Strengths-based language
      and utilization of diverse strengths among coalition members were used to effect
      change. Coalition outcomes included syringe decriminalization legislation,
      syringe exchange, naloxone access, naloxone funding legislation, and 911 Good
      Samaritan laws, along with expanded support for PWID. CONCLUSIONS: Advocacy
      successes can be applied to similar organizations in the Southern United States
      to promote harm reduction and potentially decrease HIV/AIDS burden, viral
      hepatitis, criminalization, and overdose.

PMID- 29186993
TI  - Medication use in adults with attention deficit/hyperactivity disorder in a
      commercially-insured population in the United States.
AB  - OBJECTIVE: To examine real-world prescription medication usage among commercially
      insured adults with attention deficit/hyperactivity disorder (ADHD) in the US.
      METHODS: Adults with ADHD who received >=1 ADHD medication during 2013 were
      identified from a large US claims database. Combination therapy was defined as an
      overlap of >=30 days between the index (first treatment >=30 days in 2013) and
      another medication(s). Patients were classified into six groups: long-acting (LA)
      monotherapy, short-acting (SA) monotherapy, LA + LA, SA + SA, LA + SA, and >2
      therapies. Analyses compared baseline characteristics by regimen, ranked
      combination regimens, and estimated daily average consumption (DACON) for
      monotherapy users. RESULTS: Of 206,443 adults with ADHD (mean age = 32.9 years;
      51.6% female), 56.9% used LA monotherapy, 30.7% SA monotherapy, and 12.5% used
      combination therapies (LA + SA: 10.3%; LA + LA: 1.3%; SA + SA: 0.4%; >2
      therapies: 0.5%). Extended-release mixed amphetamine salts (MAS-XR, 39.2%) and
      lisdexamfetamine (LDX, 31.5%) were the most common LA monotherapies. Nearly all
      SA monotherapy patients received immediate-release mixed amphetamine salts (MAS
      IR; 81.7%). The top three therapies among combination categories were: (a) LA +
      LA: branded MAS-XR + generic MAS-XR (13.7%), LDX + generic MAS-XR (10.8%), LDX +
      guanfacine ER (10.7%); (b) SA + SA: generic MAS-IR + clonidine IR (33.5%),
      generic MAS-IR + generic MPH SA (17.9%), branded MAS-IR + generic MAS-IR (11.1%);
      (c) LA + SA: generic MAS-XR+/-IR (39.2%), LDX + generic MAS-IR (16.7%), LA + SA
      generic MPH (12.6%). Among monotherapy users, DACON was 1.2 +/- 0.6 (LA) and 2.1
      +/- 0.9 (SA) tablets. CONCLUSIONS: There is significant treatment heterogeneity
      among US adults with ADHD. A sizable proportion of patients received
      monotherapies at above the recommended dosages or combination therapies,
      suggesting existing single-tablet regimens may not meet patients' needs.

PMID- 29186995
TI  - Toward minimally disruptive management of symptomatic endometriosis: reducing low
      value care and the burden of treatment.

PMID- 29186994
TI  - Supersonic shear imaging for the diagnosis of liver fibrosis and portal
      hypertension in liver diseases: a meta-analysis.
AB  - BACKGROUND AND AIMS: The meta-analysis aimed to summarize the technical success
      rate of supersonic shear imaging (SSI) and to evaluate the diagnostic performance
      of liver and spleen stiffness measurement (LSM and SSM) with SSI for the
      detection of liver fibrosis, portal hypertension, and gastroesophageal varices in
      liver diseases. METHODS: PubMed, EMBASE, and Cochrane Library databases were
      searched. Technical success rate of SSI was pooled. Area under curve (AUC),
      sensitivity, and specificity with corresponding 95% confidence interval (CI) were
      calculated. RESULTS: Included studies regarding the diagnostic performance of SSI
      for liver fibrosis, portal hypertension, and esophageal varices numbered 28, 4,
      and 4 respectively. The pooled technical success rates of LSM and SSM were 95.3%
      and 75.5%, respectively. The AUC, sensitivity, and specificity of LSM/SSM for
      different stages of liver fibrosis were 0.85-0.94, 0.7-0.89, and 0.82-0.92,
      respectively. The AUC, sensitivity, and specificity of LSM were 0.84 (95%CI = 0.8
      0.86), 0.79 (95%CI = 0.7-0.85), and 0.82 (95%CI = 0.72-0.88) for clinically
      significant portal hypertension, 0.85 (95%CI = 0.82-0.88), 0.8 (95%CI = 0.68
      0.88), and 0.8 (95%CI = 0.6-0.92) for any varices, and 0.86 (95%CI = 0.83-0.89),
      0.86 (95%CI = 0.76-0.92), and 0.61 (95%CI = 0.35-0.83) for high-risk varices,
      respectively. CONCLUSIONS: LSM with SSI had a high diagnostic accuracy for liver
      fibrosis, but a moderate diagnostic accuracy for portal hypertension and
      esophageal varices.

PMID- 29186996
TI  - An assessment of innovative pricing schemes for the communication of value: is
      price discrimination and two-part pricing a way forward?
AB  - INTRODUCTION: With the introduction of new expensive medicines, traditional
      pricing schemes based on constructs such as price per pill/vial have been
      challenged. Potential innovative schemes could be either financial-based or
      performance-based. Within financial-based schemes the use of price discrimination
      is an emerging option, which we explore in this assessment. Areas covered: In the
      short term the price per indication approach is likely to become more prevalent
      for high cost, high benefit new pharmaceuticals, such as those emerging in
      oncology (e.g. new combination immunotherapies). 'Two-Part Pricing' (2PP) is a
      frequently used payment method in other industries, which consists of an Entry
      Fee, giving the buyer the right to use the product, and a Usage Price charged
      every time the product is purchased. Introducing 2PP into biopharma could have
      cross-stakeholder benefits including broader patient access, and improvement in
      budget/revenue predictability. A concern however is the potential complexity of
      the negotiation between manufacturer and payer. Expert commentary: We believe
      'price discrimination' and 2PP in particular can be relevant for some new,
      expensive specialist medicines. A recommended first step would be to initiate
      pilots to test to what degree the 2PP approach meets stakeholder objectives and
      is practical to implement within specialty care.

PMID- 29186997
TI  - Western diets are not responsible for chronic acid retention: a critical analysis
      of organic acid and phosphate contribution.
AB  - According to usual literature, the diet-dependent endogenous production of
      titratable acidity (TA) is contributed by sulphuric and phosphoric acids (NA) and
      by metabolizable acids (MAs), representing 'net-endogenous acid production'
      (NEAP). NEAP is mainly neutralised by diet-dependent [Formula: see text] salts of
      inorganic cations ([Formula: see text]), estimated in foods, faeces and urine
      from inorganic cation-anion difference (NB). It is claimed that urinary loss of
      organic acids' anions, '[Formula: see text]', induces metabolizable H+ ions'
      retention. Since '[Formula: see text]' is normally lost in urine as '[Formula:
      see text]' or '[Formula: see text]', no MA retention takes place. Therefore, in
      our approach, net acid production (NAP) reduces to endogenous sulphuric acidity
      only. Since in western diets (WDs) alkaline cations exceed inorganic anions (NB
      excess), acid excess from phosphorus is neutralized. Moreover, the renal
      reabsorption of ultra-filtered Pi takes place at [Formula: see text] ratios
      greater than '4/1', which means that the kidney operates as a dietary Pi
      dependent NB generator ([Formula: see text] or [Formula: see text]). Since, in
      standard WDs, H2SO4 generation is less than '[Formula: see text]' production, the
      sulphuric acidity escaping the intestinal [Formula: see text] absorption is
      neutralized by [Formula: see text] and excreted as diet-dependent [Formula: see
      text], without interfering in normal A/B status. Only when extreme acidifying
      diets are ingested, sulphuric acidity may exceed '[Formula: see text]'. In this
      case, the excess of sulphuric acidity production is neutralised by the
      intervention of urinary [Formula: see text] excretion, whose employment is
      normally restricted to prevent loss of ultra-filtered NB. Finally, the whole body
      NA balance (NAb(W)) is calculated from the difference 'NAabs - NA(u)', where abs
      = intestinal absorption and u = urinary excretion. Being 'NAabs ~ NA(u)', NAb(W)
      approximates zero, confirming WDs as non-acidifying foods.

PMID- 29186998
TI  - Hydrothermal grain pre-processing and ultra-fine milling for the production of
      durum wheat flour fractions with high nutritional value.
AB  - This work describes a process for producing durum wheat flour fractions with high
      potential nutritional value using grain pre-milling hydrothermal treatment and
      ultra-fine grinding (micronization), coupled with air classification. The
      difference of bioactive value of the flour fractions in relation to dietary fibre
      and phenolic compounds was monitored on four durum wheat cultivars by analysing
      total arabinoxylans, water extractable arabinoxylans and 5- n-alkylresorcinols.
      The extractability of the analysed compounds was most significantly affected by
      hydrothermal treatment. On average, the hydrothermally treated kernels compared
      with the untreated ones presented a marked increase of water extractable
      arabinoxylans and alkylresorcinols (about 25 and 48%, respectively), whereas
      slightly lower total arabinoxylans content (about 9%) was detected. The air
      classification applied on micronized kernels produced two flour fractions, coarse
      and fine, with the last showing, irrespective of the hydrothermal treatment, an
      increment of alkylresorcinols (24 and 22% in untreated and treated samples) and
      of total arabinoxylans (13 and 20% in untreated and treated samples) in
      comparison with the coarse one. The fine fraction (particles <= 120 um),
      resulting richer in bioactive compounds, provides an interesting raw material to
      enrich traditional semolina in which, due to the removal of the external layers,
      the losses of total arabinoxylans and of alkylresorcinols were more than 60 and
      90% alkylresorcinols, respectively, if compared with whole wheat grain.

PMID- 29186999
TI  - Dosing strategies to optimize currently available anti-MRSA treatment options
      (Part 2: PO options).
AB  - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic
      pathogen in both outpatient and inpatient settings. Research to optimize the
      dosing of these agents is needed to slow the development of antimicrobial
      resistance and to decrease the likelihood of clinical failure. Areas covered:
      This review summarizes the available data for orally administered antimicrobials
      routinely used as monotherapy for MRSA infections. We make recommendations and
      highlight the current gaps in the literature. A PubMed (1966 - Present) search
      was performed to identify relevant literature for this review. Expert commentary:
      There is a vast divide in the amount of pharmacokinetic/pharmacodynamic data to
      guide dosing decisions for older MRSA agents compared with the oxazolidenones.
      Five-year view: Additional retrospective data will become available for the older
      MRSA agents in severe MRSA infections.

PMID- 29187000
TI  - Does myo-inositol oxygenase, the only enzyme to catalyze myo-inositol in vivo,
      play a role in the etiology of polycystic ovarian syndrome?
AB  - In polycystic ovary syndrome (PCOS), myo-inositol (MI) supplements have shown
      many beneficial effects. In this study, therefore, we aimed to investigate the
      serum level of myo-inositol oxygenase (MIOX), which is the only enzyme catalyzing
      MI in vivo, in patients with PCOS. Serum MIOX enzyme levels and other laboratory
      parameters were compared between sixty patients, who were diagnosed with PCOS for
      the first time, and sixty healthy individuals at similar age and sex. MIOX serum
      levels were not different between two groups (p = 0.7428). MIOX median and 95% CI
      were 19.4 and 10.6-39.1 in the control group and 16.4 and 7.6-46.2 in the patient
      group respectively. Demographic data, biochemical and hematological parameters,
      hormone parameters were not different except from the lymphocyte count between
      the two groups. Lymphocyte count was higher in the patient group. Although the
      ratio of LH/FSH was higher in the patient group, it was not statistically
      significant. Our results suggest that serum MIOX levels do not change in PCOS. It
      was, therefore, concluded that MI deficiency observed in PCOS was not related to
      the level of MIOX enzyme which cleaves MI.

PMID- 29187001
TI  - The Utility of Physical Activity Micro-Grants: The ParticipACTION Teen Challenge
      Program.
AB  - Youth physical activity levels remain low in Canada and worldwide. Lack of
      environmental resources (e.g., access to equipment and facilities, transportation
      options, and participation costs) is a key barrier for youth participation. Micro
      grants are small budgets of money awarded via grant applications and may help
      community organizations facilitate youth physical activity participation by
      alleviating environmental resource barriers. ParticipACTION Teen Challenge was a
      national micro-grant scheme administered in Canada. Secondary analysis of survey
      data from Provincial and Territorial coordinators, registered community
      organizers, and successful grant applicants were used to evaluate the process and
      outcomes of Teen Challenge. Results showed that the financial subsidy of 500CAD
      was used mainly toward equipment, instruction, and transportation. Coordinators
      and community organizers indicated high levels of satisfaction and benefits for
      communities and teens. A key benefit for coordinators was leveraging the Teen
      Challenge network for physical activity promotion. Reported benefits for teenaged
      participants included leadership opportunities (e.g., helping create and
      implement programs) and increased physical activity participation. Findings
      highlight the value of micro-grants for supporting sport and physical activity
      opportunities for Canadian teens, and show that such schemes address barriers
      related to environmental resources. The sustainability of micro-grant schemes
      remains to be seen.

PMID- 29187002
TI  - The influence of a diet based on flaxseed, an omega-3 source, during different
      developmental periods, on the blood pressure of rats submitted to stress.
AB  - OBJECTIVE: This study aimed to investigate a flaxseed diet during different
      developmental periods, and its effect on the blood pressure of rats submitted to
      stress. METHODS: Fifty-six male rats (F1), born from 14 rats (F0), were divided
      into seven groups (n = 8): flaxseed group (FG); flaxseed group gestation and
      lactation (FG-GL); flaxseed group weaning (FG-W); flaxseed group weaning and
      stress (FG-WS); flaxseed group stress (FG-S); flaxseed group gestation lactation
      and weaning (FG-GLW), and control Group (CG). Stress protocol was undertaken for
      1 month. Blood pressure was analysed before and after the stress protocol. The
      left adrenal glands and serum corticosterone levels were analysed. RESULTS:
      Systolic blood pressure before stress was lower in all groups with flaxseed diet
      compared with the CG (p = .00001). After stress, CG showed higher blood pressure
      compared with FG, FG-GL, and FG-GLW (p = .004). The levels of corticosterone were
      lower in the FG between all groups (p < .000001) and the CG showed higher
      compared with FG-W, FG-WS, FG-GL, and FG-GLW (p < .0001). The adrenal gland did
      not show differences. CONCLUSIONS: Results suggest a possible factor from a
      flaxseed diet against the effects of stress on a blood pressure in all periods of
      life but especially in the gestation and lactation periods.

PMID- 29187004
TI  - Personalized medicine for non-small cell lung cancer: where are we now and where
      can we go?

PMID- 29187003
TI  - The effects of chronic testosterone administration on hypothalamic gonadotropin
      releasing hormone regulatory factors (Kiss1, NKB, pDyn and RFRP) and their
      receptors in female rats.
AB  - The effects of androgens on gonadotropin-releasing hormone (GnRH) secretion in
      females have not been fully established. To clarify the direct effects of
      androgens on hypothalamic reproductive factors, we evaluated the effects of
      chronic testosterone administration on hypothalamic GnRH regulatory factors in
      ovariectomized (OVX) female rats. Both testosterone and estradiol reduced the
      serum luteinizing hormone levels of OVX female rats, indicating that, as has been
      found for estrogen, testosterone suppresses GnRH secretion via negative feedback.
      Similarly, the administration of testosterone or estradiol suppressed the
      hypothalamic mRNA levels of kisspeptin and neurokinin B, both of which are
      positive regulators of GnRH, whereas it did not affect the hypothalamic mRNA
      levels of the kisspeptin receptor or neurokinin-3 receptor. On the contrary, the
      administration of testosterone, but not estradiol, suppressed the hypothalamic
      mRNA expression of prodynorphin, which is a negative regulator of GnRH. The
      administration of testosterone did not alter the rats' serum estradiol levels,
      indicating that testosterone's effects on hypothalamic factors might be induced
      by its androgenic activity. These findings suggest that as well as estrogen,
      androgens have negative feedback effects on GnRH in females and that the
      underlying mechanisms responsible for these effects are similar, but do not
      completely correspond, to the mechanisms underlying the effects of estrogen on
      GnRH.

PMID- 29187005
TI  - Study on the activity and mechanism of skimmianine against human non-small cell
      lung cancer.
AB  - The present research was to investigate the effects of skimmianine (SK) in four
      non-small cell lung cancer (NSCLC) cells. We found that SK can significantly
      inhibit the growth of NSCLC cells and markedly induce apoptosis in NSCLC cells.
      The effects of growth inhibition and apoptosis induction were in a concentration
      response relationship and caspase-dependent manner.

PMID- 29187006
TI  - Double tinnitus in a single ear.
AB  - OBJECTIVE: To search for distinctive clinical features of patients with double
      tinnitus in a single ear. Design retrospective: Study sample: Six hundred and
      fourteen tinnitus patients were interviewed using a detailed questionnaire. They
      underwent thorough audiological evaluation. Records of seven patients reporting
      double tinnitus in 10 ears were identified and analysed. There were three women
      and four men in the group (mean age 40, range 29-49 years). RESULTS: All but two
      individuals declared sudden onset of the complaints. Three patients had been
      diagnosed with sudden sensorineural hearing loss. In all the patients, the
      components of double tinnitus were compared both to a pure tone and to a narrow
      band noise. The sounds were considered by the patients to be primary (more
      prominent) or secondary. All but one patient declared hypersensitivity to loud
      sounds. Vertigo was present in only two of the double tinnitus sufferers.
      Abnormal DPOAEs frequency values and audiogram notch frequencies were closer to
      the primary than the secondary tinnitus matches. CONCLUSIONS: In our study,
      double tinnitus was rare, mostly perceived by patients with a sudden onset of
      tinnitus. This is the first report presenting audiological findings in patients
      with double tinnitus in a single ear. Prospective search of cohorts of tinnitus
      sufferers for such patients and functional neuroimaging of their auditory
      pathways for determining underlying mechanisms of the complaints is advocated.

PMID- 29187008
TI  - Cost-effectiveness analysis of the use of high-flow oxygen through nasal cannula
      in intensive care units in NHS England.
AB  - OBJECTIVE: To estimate the cost-effectiveness of Nasal High Flow (NHF) in the
      intensive care unit (ICU) compared with standard oxygen or non-invasive
      ventilation (NIV) from a UK NHS perspective. METHODS: Three cost-effectiveness
      models were developed to reflect scenarios of NHF use: first-line therapy (pre
      intubation model); post-extubation in low-risk, and high-risk patients. All
      models used randomized control trial data on the incidence of intubation/re
      intubation, events leading to intubation/re-intubation, mortality and
      complications. NHS reference costs were primarily used. Sensitivity analyses were
      conducted. RESULTS: When used as first-line therapy, OptiflowTM NHF gives an
      estimated cost-saving of L469 per patient compared with standard oxygen and L611
      versus NIV. NHF cost-savings for high severity sub-group were L727 versus
      standard oxygen, and L1,011 versus NIV. For low-risk post-intubation patients,
      NHF generates estimated cost-saving of L156 versus standard oxygen. NHF decreases
      the number of re-intubations required in these scenarios. Results were robust in
      most sensitivity analyses. For high-risk post-intubation patients, NHF cost
      savings were L104 versus NIV. NHF results in a non-significant increase in re
      intubations required. However, reduction in respiratory failure offsets this.
      CONCLUSIONS: For patients in ICU who are at risk of intubation or re-intubation,
      NHF cannula is likely to be cost-saving.

PMID- 29187007
TI  - Glecaprevir + pibrentasvir (ABT493 + ABT-530) for the treatment of Hepatitis C.
AB  - INTRODUCTION: Glecaprevir (formerly ABT-493, pangenotypic NS3/4A protease
      inhibitor) and pibrentasvir (formerly ABT-530, pangenotypic NS5A inhibitor) are
      second generation direct acting antivirals (DAA) for the treatment of chronic
      Hepatitis C (HCV). It is a fixed dose ribavirin (RBV)-free regimen with activity
      against genotypes (GT) 1-6. In vitro the two antivirals have synergistic activity
      with a high barrier to resistance and potent activity against common
      polymorphisms. It is once daily oral dosing with minimal absorption, primary
      biliary excretion, and negligible renal excretion, making it safe for patients
      with renal impairment. This regimen is being reviewed because it is the first
      pangenotypic regimen suitable for those with renal impairment and prior DAA
      failure. Areas covered: The key phase 2 and 3 trials which investigated the
      efficacy and safety of glecaprevir/pibrentasvir are reviewed by methodology,
      primary end point, baseline demographic data, response rates, and adverse events.
      Literature search methodology involved reviewing key abstracts presented at the
      American Association for the Study of Liver Disease and European Association for
      the Study of Liver. Expert commentary: The advantages and limitations of
      glecaprevir/pibrentasvir will be reviewed in comparison to its competitor drug on
      the market.

PMID- 29187009
TI  - Ixekizumab: an anti- IL-17A monoclonal antibody for the treatment of psoriatic
      arthritis.
AB  - INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease that
      manifests itself with synovitis, dactylitis, enthesitis and also axial
      involvement. Interleukin-17A has been identified as a master cytokine in the
      inflammatory response and pathogenesis of PsA and spondyloarthritis in general.
      Ixekizumab is a new humanized monoclonal antibody that blocks the biological
      activity of IL-17A. This biological agent has previously demonstrated a high
      level of efficacy in psoriasis. Areas covered: This review discusses the basic
      immunology of the IL-17 cytokine family, the contribution of IL-17A to the
      immunopathogenesis of PsA, the clinical trials that evaluated ixekizumab in
      patients with PsA (SPIRIT program) and the safety of this agent. Expert opinion:
      Ixekizumab demonstrated its efficacy in different aspects of PsA including
      peripheral joint involvement, dactylitis, skin symptoms and patient reported
      outcomes in the 2 phase III trials from the SPIRIT program. Its safety profile
      was consistent with previous observations in patients with psoriasis. The role of
      IL-17A in the management of patients with PsA needs further clarification.
      According to EULAR recommendations for the management of PsA, IL-17A inhibitors
      may be used as second line biological DMARDs after TNF inhibitors.

PMID- 29187011
TI  - Noncardiovascular Disease and Critical Care Delivery in a Contemporary Cardiac
      and Medical Intensive Care Unit.
AB  - BACKGROUND: Noncardiovascular comorbidities and critical illness are increasing
      in cardiovascular intensive care units (CICUs). There are limited data comparing
      critical care delivery, resource utilization, and costs between contemporary
      CICUs and medical intensive care units (MICUs). METHODS: All CICU (n = 6967; 22
      748 patient-days) and MICU (n = 10 892; 39 211 patient-days) admissions to Cedars
      Sinai Medical Center, a tertiary care academic medical center, between January
      2011 and December 2016 were reviewed. Both the CICU and MICU admitted patients
      for primary cardiovascular or medical conditions during the study period, but not
      for postoperative surgical care. RESULTS: Patients admitted to the CICU were more
      frequently older, male, and had more preexisting cardiac disease ( P < .0001).
      More than one-fifth (21.4%) of CICU patients had a noncardiovascular primary
      admission diagnosis, compared to 89.2% of MICU patients. Cardiovascular intensive
      care unit patients had lower Acute Physiology and Chronic Health Evaluation III
      scores (51.1 [19.9] vs 61.1 [24.9], P < .0001) and shorter median hospital length
      of stay ( P < .001), but not in-unit stay, as compared to MICU patients.
      Mechanical ventilation, vasopressors, inotropes, renal replacement therapy,
      and/or blood transfusion were required in 35.0% of CICU patients compared with
      62.2% of MICU patients ( P < .0001). The unit mortality rate was lower for CICU
      than MICU patients (4.8% vs 13.0%, P < .0001), as was the hospital mortality rate
      (9.3% vs 21.6%, P < .0001). The standardized mortality ratio was 0.73 for the
      CICU and 0.86 for the MICU. There was no difference in the mean direct cost of
      care per patient-day between the CICU and MICU ($4011 USD [376] vs $3990 USD
      [214], P = .77). CONCLUSIONS: The burden of noncardiovascular diseases and the
      requirement for critical care therapies are high in contemporary CICU patients
      but remain lower compared to the MICU population. Our findings support the
      growing complexity of care in tertiary CICUs. Further studies are required to
      explore the association between critical care delivery and outcomes in this
      evolving population.

PMID- 29187012
TI  - Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine
      kinase inhibitors.
AB  - INTRODUCTION: Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define
      important molecular subgroups of advanced non-small cell lung cancer (NSCLC). The
      identification of these genetic driver alterations created new potential for
      highly active therapeutic interventions. After discovery of ALK rearrangements in
      NSCLC, it was recognized that these confer sensitivity to ALK inhibition. Areas
      covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially
      approved as second-line treatment of ALK-positive advanced NSCLC but after this,
      it was firmly established as the standard first-line therapy for advanced ALK
      positive NSCLC. After initial response to crizotinib, tumors inevitably relapse.
      Next-generation ALK inhibitors, more potent and brain-penetrable than crizotinib,
      may be effective in re-inducing remissions when cancers are still addicted to
      ALK. Ceritinib and alectinib are approved for metastatic ALK positive NSCLC
      patients, while brigatinib received granted accelerated approval by the United
      States Food and Drug Administration. Regarding ROS1 rearrangement, to date
      crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as
      treatment of ROS1 positive advanced NSCLC. Expert commentary: Although novel ALK
      inhibitors are under clinical investigation compared to crizotinib as front-line
      treatment for ALK-positive NSCLC, nowadays the current standard first-line
      therapy for these patients is crizotinib. Further research will clarify the best
      management of ALK-positive NSCLC, above all who progress on first-line
      crizotinib.

PMID- 29187013
TI  - Engineered tubular structures based on chitosan for tissue engineering
      applications.
AB  - The development of versatile tubular structures is a subject of broad interest in
      tissue engineering applications. Herein, we demonstrate the production of tubular
      structures based on chitosan through a combination of dipping, freeze-drying and
      supercritical technology approaches. The combination of these techniques yields
      versatile tubes with a perfectly defined hollow imprint, which upon chemical
      cross-linking with genipin acquire enhanced mechanical properties (Young Modulus
      ( E) and ultimate tensile stress (sigmamax)), as well as improved stability in
      wet conditions. The biological performance reveals that cells remain attached,
      well-spread and viable on the surface of cross-linked tubes. As so, is envisioned
      that our methodology opens up new avenues on tissue engineering approaches, where
      the design of tubular structures with tuned length, diameter and elasticity is
      required.

PMID- 29187014
TI  - Fenestrated TEVAR Using a Guidewire Fixator for Anchoring in Aortic Arch Target
      Vessels.
AB  - PURPOSE: To report a new facilitated method for securing target vessel access
      during single fenestrated and branched thoracic endovascular repair using a
      guidewire fixator. TECHNIQUE: The Liungman Guidewire Fixator (LGF) includes a
      0.035-inch guidewire that is fitted with a stopper close to the distal end and a
      self-expanding anchoring element that is freely movable over the guidewire to the
      point of the stopper. The technique of using a LGF for anchoring in a target
      vessel is described in a 75-year-old woman with a 53-mm saccular arch aneurysm.
      She was treated with a fenestrated Zenith stent-graft that had a catheter
      preloaded fenestration for the left subclavian artery (LSA) and a scallop for the
      left common carotid artery. To avoid through-and-through wire and brachial
      access, the LGF was used to secure the guidewire in the LSA during stent-graft
      deployment. CONCLUSION: The use of an LGF for anchoring in the target LSA during
      fenestrated arch endografting was feasible and safe.

PMID- 29187015
TI  - Submitral Aneurysm After Pulmonary Artery Banding-A Case Report.
AB  - Submitral aneurysms are rare clinical entities occurring predominantly in young
      adults of African descent. A host of etiologies have been proposed for this
      entity. We present a unique case of submitral aneurysm which developed after
      pulmonary artery banding in a three-year-old girl with complex congenital heart
      disease. The aneurysmal sac was burrowing into the interatrial septum.

PMID- 29187016
TI  - Adolescent Female With Turner's Syndrome and 46,X,der(Y) del(Y)(p11.2)del(q11.2)
      Karyotype With Gonadoblastoma and Dysgerminoma.
AB  - Gonadal dysgenesis patients with Y chromosomal material are subject to increased
      risk for germ cell tumors. We report a case of an adolescent female presenting
      with Turner-like syndrome with primary amenorrhea and Tanner stage 1 breast
      development. Karyotype showed one X chromosome and a minute pericentromeric
      fragment of Y chromosome without any functional Y genes in all the cells, unlike
      a mosaic pattern, represented as 46,X,der(Y)del(Y)(p11.2)del(q11.2). Laparoscopic
      bilateral gonadectomy was performed due to presence of Y chromosome material and
      histopathology confirmed gonadoblastoma with a focus of dysgerminoma of the right
      ovary. A robotic-assisted surgical staging for dysgerminoma was performed which
      was confirmed to be negative for malignancy. This points at the putative genes
      for gonadoblastoma to be present around the centromere of the Y chromosome.

PMID- 29187017
TI  - Anti-apoptotic effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose)
      polymerase, against multiple organ damage induced by gamma irradiation in rats.
AB  - PURPOSE: This study aimed to investigate the effect of 3-aminobenzamide (3-AB) in
      doses of 5, 10 and 15 mg/kg on the inhibition of Poly (ADP-ribose) polymerase
      (PARP) when combined with ionizing radiation (IR). MATERIAL AND METHODS: Rats
      were treated intraperitonealy, one hour prior to irradiation at a dose level of 6
      Gray (Gy) and were sacrificed 24 hours after irradiation. Control groups were run
      concurrently. RESULTS: IR led to an increase of thiobarbituric acid reactive
      substance (TBARS), nitrite as well as a decrease in total antioxidant capacity
      associated increase in myeloperoxidase (MPO) with the expression of
      cyclooxygenase-2 (COX-2). Moreover, IR caused an increase in serum lactate
      dehydrogenase (LDH) activity and cytosolyic Ca+2 associated with an expression of
      Caspase-3 as well as a decline in complex-I activity and adenosine triphosphate
      (ATP) level. Pretreatment with 5 and 10 mg/kg of 3AB guarded against the changes
      in all the measured parameters, conversely the dose of 15 mg/kg showed no effect
      on the damage induced by irradiation in the selected tissues. Moreover, 3AB has a
      dose-dependent effect on viability of Vero cells. CONCLUSION: The selected low
      doses of 3AB rather than the higher dose (15 mg/kg) protected against radiation
      induced multiple organ damage.

PMID- 29187019
TI  - Microfluidic system for synthesis of nanofibrous conductive hydrogel and muscle
      differentiation.
AB  - Microscale hydrogels can be synthesized within microfluidic systems and
      subsequently assembled to make tissues composed of units such as myofibers in
      muscle tissue. Importantly, the nanofibrous surface of hydrogels is essential for
      tissue engineering aims due to inducing beneficial cell-surface interactions. In
      this study, a new microfluidic platform, embedded with a hydrogel, was introduced
      that allowed for performing multiple non-parallel steps for the synthetic
      approaches. Satellite cells, isolated from skeletal tissues of 10-day Naval
      Medical Research Institute-murine were cultured on the prepared hydrogel within
      the microfluidic system. The normal proliferation of satellite cells occurred
      after the employment of continuous perfusion cell culture. Interestingly, the
      positive results of the immuno-staining assay along with the cellular bridge
      formation between hydrogel fragments confirmed the muscle differentiation of
      seeded satellite cells. Further on, COMSOl simulations anticipated that the
      thermodynamic conditions of the microfluidic system during hydrogel synthesis had
      to be kept steady while a shear stress value of 15 * 10-6 Pa was calculated,
      exhibiting a cell culture condition free of environmental stress.

PMID- 29187020
TI  - A Rare Case of Pediatric Chronic Myelogenous Leukemia Presenting With Severe
      Thrombocytosis Without Leukocytosis.
AB  - Pediatric chronic myelogenous leukemia is uncommon. We report a pediatric patient
      with chronic myelogenous leukemia presenting with a normal white blood cell count
      and no circulating immature myeloid cells. The patient presented with extreme
      thrombocytosis (platelet count range: 2175-3064 * 109/L) noted incidentally. No
      splenomegaly was found. Examination of the bone marrow aspirate revealed normal
      cellularity and normal myeloid: erythroid ratio with marked megakaryocytic
      hyperplasia. Molecular studies on the bone marrow aspirate detected both the
      major BCR/ABL1 p210 fusion transcript (9280 copies; p210/ ABL1 ratio: 38.2%) and
      the minor p190 transcript (below limit of quantitation). The platelet count
      normalized within 2 weeks after treatment with the second-generation tyrosine
      kinase inhibitor dasatinib. Follow-up after 3 months revealed a 1.87 log
      reduction in p210 transcripts compared to diagnosis and no detectable p190
      transcripts. This case highlights the need to include BCR/ABL1 fusion testing to
      accurately diagnose pediatric patients presenting with isolated thrombocytosis.

PMID- 29187021
TI  - Correction to: Alizadeh et al., Association of transcription factor 4 (TCF4) gene
      mRNA level with schizophrenia, its psychopathology, intelligence and cognitive
      impairments.

PMID- 29187018
TI  - Targeting methionine with oral recombinant methioninase (o-rMETase) arrests a
      patient-derived orthotopic xenograft (PDOX) model of BRAF-V600E mutant melanoma:
      implications for chronic clinical cancer therapy and prevention.
AB  - The elevated methionine (MET) use by cancer cells is termed MET dependence and
      may be the only known general metabolic defect in cancer. Targeting MET by
      recombinant methioninase (rMETase) can arrest the growth of cancer cells in vitro
      and in vivo. We previously reported that rMETase, administrated by intra
      peritoneal injection (ip-rMETase), could inhibit tumor growth in a patient
      derived orthotopic xenograft (PDOX) model of a BRAF-V600E mutant melanoma. In the
      present study, we compared ip-rMETase and oral rMETase (o-rMETase) for efficacy
      on the melanoma PDOX. Melanoma PDOX nude mice were randomized into four groups of
      5 mice each: untreated control; ip-rMETase (100 units, i.p., 14 consecutive
      days); o-rMETase (100 units, p.o., 14 consecutive days); o-rMETase+ip-rMETase
      (100 units, p.o.+100 units, i.p., 14 consecutive days). All treatments inhibited
      tumor growth on day 14 after treatment initiation, compared to untreated control
      (ip-rMETase, p<0.0001; o-rMETase, p<0.0001; o-rMETase+ip-rMETase, p<0.0001). o
      rMETase was significantly more effective than ip-rMETase (p = 0.0086). o
      rMETase+ip-rMETase was significantly more effective than either mono-therapy: ip
      rMETase, p = 0.0005; or o-rMETase, p = 0.0367. The present study is the first
      demonstrating that o-rMETase is effective as an anticancer agent. The results of
      the present study indicate the potential of clinical development of o-rMETase as
      an agent for chronic cancer therapy and for cancer prevention and possibly for
      life extension since dietary MET reduction extends life span in many animal
      models.

PMID- 29187022
TI  - "Chorea": A Unique Presentation of Left Atrial Myxoma in a Pediatric Patient.
AB  - We report an unusual presentation of a large left atrial myxoma in an eight-year
      old girl who presented with the sudden onset of chorea. This case illustrates the
      fact that the presentation of chorea in nonendemic areas for rheumatic fever
      should raise suspicion for a myxoma. The chorea resolved soon after removal of
      the myxoma, supporting the hypothesis of an immune-mediated mechanism, or
      manifestation of paraneoplastic syndrome secondary to the myxoma.

PMID- 29187023
TI  - Biopsy-proven Hepatocellular Carcinoma in a 53-year-old Woman With Arginase
      Deficiency.
AB  - Arginase 1 deficiency, the least common urea cycle disorder, commonly presents
      with childhood-onset spastic paraplegia, progressive neurologic impairment,
      epilepsy, and developmental delay or regression. Biopsy-proven cirrhosis and
      hepatocellular carcinoma diagnosed via clinical and imaging studies (but without
      biopsy confirmation) have been previously reported. We report, herein, a case of
      a 53-year-old woman with arginase 1 deficiency who developed symptoms of
      "abdominal bloating." Imaging studies (ultrasound and magnetic resonance imaging)
      demonstrated 2 dominant hepatic masses, measuring 5.9 cm and 5.7 cm in greatest
      dimensions and located in hepatic segments 5 and 6, respectively. Core biopsies
      of the lesions demonstrated well-differentiated hepatocellular carcinoma.
      Immunohistochemistry performed on the segment 5 lesion was negative for arginase
      1. This report represents, to the best of our knowledge, the first case of biopsy
      proven hepatocellular carcinoma in an individual with arginase 1 deficiency.

PMID- 29187024
TI  - Ossifying Renal Tumor of Infancy: Report of a Case With Positive WT1
      Immunohistochemistry and High Mitotic Index and Review of the Literature.
AB  - Ossifying renal tumor of infancy (ORTI) is a rare, benign pediatric tumor of the
      kidney. Since first reported by Chatten in 1980, 23 cases have been published.
      Previous authors have argued that ORTI might originate from nephrogenic rests,
      thereby sharing a pathogenic relationship with Wilms' tumor (WT). ORTI is
      characterized histologically by a population of polygonal osteoblast-like cells
      around an osteoid core and densely cellular component of blastemal-like or
      spindle cells. While the immunohistochemical profile of the cellular components
      has been reported, to the best of our knowledge, the status of WT1 expression has
      only been reported once, where it showed negative marking. Mitoses have been
      described only sporadically in this neoplasm. We report on a case of ORTI with
      positive WT1 immunohistochemical marking and numerous mitoses. This case
      highlights a possible pitfall for misdiagnosing ORTI as a WT and provides
      additional insight into its pathogenesis.

PMID- 29187025
TI  - Positive Aspects of Caregiving and Caregiver Burden: A Study of Caregivers of
      Patients With Dementia.
AB  - BACKGROUND: Now positive aspect of caregiving (PAC) is well-defined as caregiver
      gains, satisfaction, meaningful life, and enhanced family relationship. The
      adjusted association of PAC and caregiver burden is not well acknowledged. This
      study investigated the association of caregiver burden and PAC adjusting for
      potential confounders. METHODS: This was a cross-sectional study that recruited
      132 caregivers. A linear regression model with PAC was used to estimate the
      adjusted associations. RESULTS: The caregiver burden was negatively associated
      with PAC (mean difference in PAC per a 1-unit increase in caregiver burden = 
      0.12, 95% confidence interval: -0.18 to -0.056; P < .001). This association
      remained after adjustment for caregivers' age and marital status as well as
      patients' dependency level. CONCLUSION: The negative significant association of
      caregiver burden with PAC reinforces the need for interventional and/or
      educational programs aiming at decreasing the overall imposed burden. This can
      play an important role in improving caregivers' general health and quality of
      life.

PMID- 29187026
TI  - The Relationship Between Social Cognition and Awareness in Alzheimer Disease.
AB  - A large body of evidence highlights the social cognitive impairment in
      neurodegenerative diseases such Alzheimer disease (AD). This study investigated
      the relationship among social and emotional functioning (SEF), awareness of
      disease, and other clinical aspects in people with AD (PwAD). A consecutive
      series of 50 people with mild to moderate AD and their 50 family caregivers were
      assessed. There was a significant difference between self-rated SEF and informant
      rated SEF. In 56% of PwAD, self-rated SEF is lower than informant-rated SEF.
      People with AD mostly presented with mildly impaired awareness of the disease
      (56%), 20% had moderately impaired awareness of the disease, and 6% were unaware
      of the disease. The multivariate linear regression showed that informant-rated
      SEF was related to the social functioning, and relationships, domains of
      awareness of disease, and the PwAD informant-rated quality of life. The
      relationship between SEF and awareness of social functioning and relationship
      domain shows that they are comprised of judgments related to perceptions about
      oneself, values, and beliefs qualitatively different from awareness of memory or
      functionality, which can be directly observed.

PMID- 29187027
TI  - Actual versus recommended storage temperatures of oral anticancer medicines at
      patients' homes.
AB  - Background Substantial quantities of unused medicines are returned by patients to
      the pharmacy each year. Redispensing these medicines would reduce medicinal waste
      and health care costs. However, it is not known if medicines are stored by
      patients as recommended in the product label. Inadequate storage may negatively
      affect the medicine and reduce clinical efficacy whilst increasing the risk for
      side effects. Objective To investigate the proportion of patients storing oral
      anticancer medicines according to the temperature instructions in the product
      label. Methods Consenting adult patients from six Dutch outpatient hospital
      pharmacies were included in this study if they used an oral anticancer medicine
      during February 2014 - January 2015. Home storage temperatures were assessed by
      inclusion of a temperature logger in the original cancer medicines packaging. The
      primary outcome was the proportion of patients storing oral anticancer medicines
      as specified in the Summary of Product Characteristics, either by recalculating
      the observed temperature fluctuations to a single mean kinetic temperature or by
      following the temperature instructions taking into account a consecutive 24-h
      tolerance period. Results Ninety (81.1%) of the 111 included patients (47.8%
      female, mean age 65.2 (SD: 11.1)) returned their temperature loggers to the
      pharmacy. None of the patients stored oral anticancer medicines at a mean kinetic
      temperature above 25C, one patient stored a medicine requiring storage below 25C
      longer than 24 h above 25C. None of the patients using medicines requiring
      storage below 30C kept their medicine above 30C for a consecutive period of 24 h
      or longer. Conclusion The majority of patients using oral anticancer medicines
      store their medicines according to the temperature requirements on the product
      label claim. Based on our results, most oral anticancer medicines will not be
      negatively affected by temperature conditions at patients' homes for a maximum of
      three months and are likely to be suitable for redispensing.

PMID- 29187028
TI  - Rat Model of Brain Injury to Occupants of Vehicles Targeted by Land Mines:
      Mitigation by Elastomeric Frame Designs.
AB  - Many victims of blast traumatic brain injury (TBI) are occupants of vehicles
      targeted by land mines. A rat model of under-vehicle blast TBI was used to test
      the hypothesis that the ensuing neuropathology and altered behavior are mitigated
      by vehicle frame designs that dramatically reduce blast-induced acceleration (G
      force). Male rats were restrained on an aluminum platform that was accelerated
      vertically at up to 2850g, in response to detonation of an explosive positioned
      under a second platform in contact with the top via different structures. The
      presence of elastomeric, polyurea-coated aluminum cylinders between the platforms
      reduced acceleration by 80% to 550g compared with 2350g with uncoated cylinders.
      Moreover, 67% of rats exposed to 2850g, and 20% of those exposed to 2350g died
      immediately after blast, whereas all rats subjected to 550g blast survived.
      Assays for working memory (Y maze) and anxiety (Plus maze) were conducted for up
      to 28 days. Rats were euthanized at 24 h or 29 days, and their brains were used
      for histopathology and neurochemical measurements. Rats exposed to 2350g blasts
      exhibited increased cleaved caspase-3 immunoreactive neurons in the hippocampus.
      There was also increased vascular immunoglobulin (Ig)G effusion and F4/80
      immunopositive macrophages/microglia. Blast exposure reduced hippocampal levels
      of synaptic proteins Bassoon and Homer-1, which were associated with impaired
      performance in the Y maze and the Plus maze tests. These changes observed after
      2350g blasts were reduced or eliminated with the use of polyurea-coated
      cylinders. Such advances in vehicle designs should aid in the development of the
      next generation of blast-resistant vehicles.

PMID- 29187029
TI  - Comparison of different approaches for identifying subnetworks in metabolic
      networks.
AB  - A metabolic network model provides a computational framework for studying the
      metabolism of a cell at the system level. The organization of metabolic networks
      has been investigated in different studies. One of the organization aspects
      considered in these studies is the decomposition of a metabolic network. The
      decompositions produced by different methods are very different and there is no
      comprehensive evaluation framework to compare the results with each other. In
      this study, these methods are reviewed and compared in the first place. Then they
      are applied to six different metabolic network models and the results are
      evaluated and compared based on two existing and two newly proposed criteria.
      Results show that no single method can beat others in all criteria but it seems
      that the methods introduced by Guimera and Amaral and Verwoerd do better on among
      metabolite-based methods and the method introduced by Sridharan et al. does
      better among reaction-based ones. Also, the methods are applied to several
      artificial networks, each constructed from merging a few KEGG pathways. Then,
      their capability to recover those pathways are compared. Results show that among
      metabolite-based methods, the method of Guimera and Amaral does better again,
      however, no notable difference between the performances of reaction-based methods
      was detected.

PMID- 29187030
TI  - Hemophagocytic Lymphohistiocytosis Secondary to T Cell/Histiocyte-rich Large B
      Cell Lymphoma in an Adolescent Male.
AB  - Hemophagocytic Lymphohistiocytosis (HLH) is a hyperinflammatory disorder that may
      be encountered as a primary or secondary phenomenon. HLH secondary to lymphoma
      has been described, more frequently in adults than in children. T-cell/Histiocyte
      rich B-cell lymphoma (THRLBCL) is a large B-cell lymphoma that resides in a
      microenvironment of robust host immune response and has previously been
      associated with HLH in adults. Here, we describe the first case of HLH secondary
      to THRLBCL in an adolescent patient.

PMID- 29187031
TI  - Minocycline plus N-Acetylcysteine Reduce Behavioral Deficits and Improve
      Histology with a Clinically Useful Time Window.
AB  - There are no drugs to manage traumatic brain injury (TBI) presently. A major
      problem in developing therapeutics is that drugs to manage TBI lack sufficient
      potency when dosed within a clinically relevant time window. Previous studies
      have shown that minocycline (MINO, 45 mg/kg) plus N-acetylcysteine (NAC, 150
      mg/kg) synergistically improved cognition and memory, modulated inflammation, and
      prevented loss of oligodendrocytes that remyelinated damaged white matter when
      first dosed 1 h after controlled cortical impact (CCI) in rats. We show that MINO
      (45 mg/kg) plus NAC (150 mg/kg) also prevent brain injury in a mouse closed head
      injury (CHI) TBI model. Using the CHI model, the concentrations of MINO and NAC
      were titrated to determine that MINO (22.5 mg/kg) plus NAC (75 mg/kg) was more
      potent than the original formulation. MINO (22.5 mg/kg) plus NAC (75 mg/kg) also
      limited injury in the rat CCI model. The therapeutic time window of MINO plus NAC
      was then tested in the CHI and CCI models. Mice and rats could acquire an active
      place avoidance task when MINO plus NAC was first dosed at 12 h post-injury. A
      first dose at 12 h also limited gray matter injury in the hippocampus and
      preserved myelin in multiple white matter tracts. Mice and rats acquired Barnes
      maze when MINO plus NAC was first dosed at 24 h post-injury. These data suggest
      that MINO (22.5 mg/kg) plus NAC (75 mg/kg) remain potent when dosed at clinically
      useful time windows. Both MINO and NAC are drugs approved by the Food and Drug
      Administration and have been administered safely to patients in clinical trials
      at the doses in the new formulation. This suggests that the drug combination of
      MINO plus NAC may be effective in treating patients with TBI.

PMID- 29187032
TI  - Postmortem Diagnostic Exome Sequencing Identifies a De Novo TUBB3 Alteration in a
      Newborn With Prenatally Diagnosed Hydrocephalus and Suspected Walker-Warburg
      Syndrome.
AB  - Objective Herein, we report a case of a deceased newborn with prenatally detected
      hydrocephalus. Postnatal findings included abnormal brain imaging and
      electroencephalogram, optic nerve abnormalities, and elevated creatine kinase
      (CK). No underlying genetic etiology had been previously identified for the
      proband, despite testing with a congenital muscular dystrophy gene panel. Methods
      Diagnostic exome sequencing (DES) was performed on the proband-parents trio, and
      candidate alterations were confirmed using automated fluorescence dideoxy
      sequencing. Results Exome sequencing of the proband, mother and father identified
      a previously unreported apparently de novo heterozygous tubulin, beta-3 ( TUBB3)
      c.523G>C (p.V175L) alteration in the proband. Conclusion Overall, DES established
      a likely molecular genetic diagnosis for a postmortem case after traditional
      testing methods were uninformative. The DES results allowed for reproductive
      options, such as preimplantation genetic diagnosis and/or prenatal diagnosis, to
      be available to the parents in future pregnancies.

PMID- 29187033
TI  - Second re-irradiation: a narrative review of the available clinical data.
AB  - BACKGROUND: Considerable controversy exists about the safety and efficacy of
      second re-irradiations (three courses of radiotherapy to overlapping volumes).
      Therefore, all published clinical studies were reviewed. MATERIAL AND METHODS:
      Contemporary and historical articles were identified. Outcomes such as survival,
      local control, symptom improvement and side effects were extracted. Contemporary
      results were grouped by anatomical location of the re-irradiated region in the
      body. RESULTS: Most data were derived from central nervous system tumors, pelvic
      tumors and bone metastases. We could include nine contemporary, retrospective
      studies with 2-25 patients each. Nearly, all patients were treated with
      palliative intent. Most of the prescribed re-irradiation regimens were highly
      individualized and thus difficult to compare. Symptomatic responses were recorded
      in most patients. In palliatively treated patients with pelvic and bony target
      volumes, high-grade toxicity was uncommon. CONCLUSIONS: Despite of issues related
      to study size, length of follow-up and calculation of lifetime cumulative
      equivalent dose, the available data provide an initial framework for future
      studies and discussion of dose constraints. Selected dose-fractionation regimens
      may result in a satisfactory therapeutic ratio even after two previous courses of
      radiotherapy, if these were well tolerated.

PMID- 29187034
TI  - Growth Restriction, Osteopenia, Placental Massive Perivillous Fibrin Deposition
      With (or Without) Intervillous Histiocytes and Renal Tubular Dysgenesis-An
      Emerging Complex.
AB  - We describe a case of a pregnancy complicated by early onset asymmetric growth
      restriction with anhydramnios with termination occurring at 21 weeks. Fetal
      autopsy showed demineralization of bones and renal tubular dysgenesis. Placental
      pathology showed features of massive perivillous fibrin deposition and chronic
      histiocytic intervillositis. We review prior documentation of this association
      and briefly discuss potential pathogenesis.

PMID- 29187035
TI  - Immobilisation of hydroxyapatite-collagen on polydopamine grafted stainless steel
      316L: Coating adhesion and in vitro cells evaluation.
AB  - The utilisation of hydroxyapatite and collagen as bioactive coating materials
      could enhance cells attachment, proliferation and osseointegration. However, most
      methods to form crystal hydroxyapatite coating do not allow the incorporation of
      polymer/organic compound due to production phase of high sintering temperature.
      In this study, a polydopamine film was used as an intermediate layer to
      immobilise hydroxyapatite-collagen without the introduction of high sintering
      temperature. The surface roughness, coating adhesion, bioactivity and osteoblast
      attachment on the hydroxyapatite-collagen coating were assessed as these
      properties remains unknown on the polydopamine grafted film. The coating was
      developed by grafting stainless steel 316L disks with a polydopamine film.
      Collagen type I fibres were then immobilised on the grafted film, followed by the
      biomineralisation of hydroxyapatite. The surface roughness and coating adhesion
      analyses were later performed by using AFM instrument. An Alamar Blue assay was
      used to determine the cytotoxicity of the coating, while an alkaline phosphatase
      activity test was conducted to evaluate the osteogenic differentiation of human
      fetal osteoblasts on the coating. Finally, the morphology of cells attachment on
      the coating was visualised under FESEM. The highest RMS roughness and coating
      adhesion were observed on the hydroxyapatite-collagen coating (hydroxyapatite
      coll-dopa). The hydroxyapatite-coll-dopa coating was non-toxic to the osteoblast
      cells with greater cells proliferation, greater level of alkaline phosphate
      production and more cells attachment. These results indicate that the
      immobilisation of hydroxyapatite and collagen using an intermediate polydopamine
      is identical to enhance coating adhesion, osteoblast cells attachment,
      proliferation and differentiation, and thus could be implemented as a coating
      material on orthopaedic and dental implants.

PMID- 29187036
TI  - Persistence of Villous Immaturity in Term Deliveries Following Intrauterine
      Transfusion for Parvovirus B19 Infection and RhD-associated Hemolytic Disease of
      the Fetus and Newborn.
AB  - Common causes of fetal anemia and hydrops include parvovirus B19 infection during
      the first 2 trimesters of pregnancy, as well as maternal alloimmunization to RhD
      with subsequent hemolytic disease of the fetus and newborn (HDFN) in an RhD
      positive fetus. Although both of these conditions have historically caused
      significant fetal morbidity and mortality, the advent of intrauterine transfusion
      (IUT) over the last few decades has dramatically improved outcomes. Prior
      literature has extensively documented placental changes associated with untreated
      parvovirus infection and RhD HDFN in intrauterine fetal demises and preterm
      births; however, histopathologic changes in term placentas from term infants
      treated with IUT have not been reported. We present placental findings in 2 cases
      of parvovirus B19-associated hydrops and 2 cases of RhD HDFN-associated hydrops
      in term infants after IUT, highlighting unique aspects that may be diagnostically
      useful for the examining pathologist.

PMID- 29187037
TI  - Modeling a Predictive Energy Equation Specific for Maintenance Hemodialysis.
AB  - BACKGROUND: Hypermetabolism is theorized in patients diagnosed with chronic
      kidney disease who are receiving maintenance hemodialysis (MHD). We aimed to
      distinguish key disease-specific determinants of resting energy expenditure to
      create a predictive energy equation that more precisely establishes energy needs
      with the intent of preventing protein-energy wasting. MATERIALS AND METHODS: For
      this 3-year multisite cross-sectional study (N = 116), eligible participants were
      diagnosed with chronic kidney disease and were receiving MHD for at least 3
      months. Predictors for the model included weight, sex, age, C-reactive protein
      (CRP), glycosylated hemoglobin, and serum creatinine. The outcome variable was
      measured resting energy expenditure (mREE). Regression modeling was used to
      generate predictive formulas and Bland-Altman analyses to evaluate accuracy.
      RESULTS: The majority were male (60.3%), black (81.0%), and non-Hispanic (76.7%),
      and 23% were >=65 years old. After screening for multicollinearity, the best
      predictive model of mREE ( R2 = 0.67) included weight, age, sex, and CRP. Two
      alternative models with acceptable predictability ( R2 = 0.66) were derived with
      glycosylated hemoglobin or serum creatinine. Based on Bland-Altman analyses, the
      maintenance hemodialysis equation that included CRP had the best precision, with
      the highest proportion of participants' predicted energy expenditure classified
      as accurate (61.2%) and with the lowest number of individuals with
      underestimation or overestimation. CONCLUSIONS: This study confirms disease
      specific factors as key determinants of mREE in patients on MHD and provides a
      preliminary predictive energy equation. Further prospective research is necessary
      to test the reliability and validity of this equation across diverse populations
      of patients who are receiving MHD.

PMID- 29187038
TI  - Does Having a Relative in Dialysis Therapy Affect Attitudes Toward Kidney
      Donating?
AB  - CONTEXT: The majority of kidney transplants in Turkey are performed from live
      donors and from those among first-degree relatives. OBJECTIVE: To compare the
      view points and the attitudes of individuals who have relatives undergoing
      dialysis toward kidney donation treatment with those who do not. DESIGN: The
      study was designed as a descriptive study, which used simple random sampling.
      SETTING: The sample consisted of 204 individuals, divided into 2 groups: those
      whose relatives underwent dialysis treatment (group A, n = 106) and those whose
      relatives did not (group B, n = 98). RESULTS: The means of the total points
      obtained in "Kidney Donation Attitude Inventory" (KDAI) by individuals in group A
      were statistically significantly higher than those obtained by individuals in
      group B ( P = .001). Although there was a statistically significant difference in
      the educational status, status of willing to donate their kidneys and being a
      relative of an individual awaiting a kidney transplant, and the mean total points
      obtained from the KDAI between the groups ( P < .05), no statistically
      significant difference was determined between the means of the obtained total
      points and the gender and the duration of dialysis treatment ( P > .05).
      CONCLUSION: The attitudes of the relatives of individuals undergoing dialysis
      treatment toward kidney donation were determined to be more positive.

PMID- 29187039
TI  - Representaciones sociales sobre la problematica de Chagas en un servicio de salud
      comunitaria del Gran La Plata, Buenos Aires, Argentina.
AB  - Hablar de Chagas es hablar de una problematica compleja, definida por elementos
      de caracter biomedico, epidemiologico, sociocultural y politico, que se conjugan
      dinamicamente. En este trabajo buscamos identificar y analizar las
      representaciones sobre Chagas de los integrantes del equipo de salud de un centro
      de atencion periurbano de la ciudad de La Plata, Argentina. Mediante un abordaje
      cualitativo, se realizaron entrevistas semiestructuradas y se analizaron las
      respuestas con la tecnica del analisis de contenido. Los resultados mostraron que
      la mayor parte de las personas entrevistadas no contempla al Chagas como una
      problematica en su contexto laboral cotidiano y manifiestan un fuerte sesgo
      biologicista en su formacion profesional. Con este trabajo senalamos la urgente
      necesidad de reflexionar criticamente en torno a la formacion de los
      profesionales de la salud en relacion a problematicas socioambientales complejas
      de importancia regional, como lo es el Chagas.

PMID- 29187040
TI  - Parenteral Soybean Oil Induces Hepatosteatosis Despite Addition of Fish Oil in a
      Mouse Model of Intestinal Failure-Associated Liver Disease.
AB  - BACKGROUND: Replacement of parenteral soybean oil (SO) with fish oil (FO) is an
      effective therapy for intestinal failure-associated liver disease (IFALD) in
      children. However, practitioners remain concerned about the risk of essential
      fatty acid deficiency (EFAD) and sometimes treat IFALD with a combination of 50%
      SO and 50% FO emulsions. The purpose of this study was to determine if mixing 50%
      SO and 50% FO emulsions would prevent hepatosteatosis in a murine model of
      parenteral nutrition (PN)-induced hepatosteatosis. METHODS: C57BL/6 mice were
      randomized to receive oral PN with parenteral saline, FO, SO, or a mixture of 50%
      FO and 50% SO for 19 days. Fatty acid analysis, histologic evaluation,
      Nonalcoholic Steatohepatitis Clinical Research Network (NSCRN) scores, and
      reverse-transcriptase polymerase chain reaction for key lipogenic genes were
      performed. RESULTS: The PN + saline group was the only group with EFAD, with a
      serum and hepatic triene/tetraene ratio of 0.53. NSCRN scores were highest in the
      PN + SO group (5.5; 95% confidence interval [CI], 4.9-6.1), followed by the PN +
      FO/SO (4.5; 95% CI, 3.5-5.5) group, with the lowest score in the PN + FO (2.0;
      95% CI, 1.1-2.9) group. Acetyl CoA carboxylase alpha and acetyl CoA carboxylase
      beta expression was lower in the PN + FO group than in the PN + FO/SO or PN + SO
      groups. CONCLUSIONS: Our data demonstrate that a mixed fat emulsion of 50% SO and
      50% FO is inferior to 100% FO in reducing hepatosteatosis in this model. These
      data suggest that use of parenteral SO with parenteral FO, in a 1:1 ratio, may
      still contribute to liver injury, although it is less hepatotoxic than pure SO.

PMID- 29187042
TI  - Effect of Discontinuation of Manganese Supplementation From Home Parenteral
      Nutrition Solutions on Whole-Blood Levels and Magnetic Resonance Imaging of the
      Brain: A 5-Year Cohort Study.
AB  - BACKGROUND: Manganese (Mn) is included in current premixed multiple trace element
      (TE) additives for home parenteral nutrition (HPN). However, there is a risk of
      oversupplementation of Mn due to contamination from PN additives.
      Oversupplementation can produce Mn toxicity with neurologic symptoms and
      abnormalities on brain magnetic resonance imaging (MRI). In 2009, we reported
      that whole-blood Mn levels were above the upper limit of normal in 16 HPN
      patients, with 81% having MRI findings. Subsequently, we removed Mn
      supplementation from all our HPN patients. We present a 5-year follow-up here.
      METHODS: This is a prospective cohort study on 11 of the surviving 16 patients on
      HPN. All patients had Mn removed from PN and had yearly monitoring of blood Mn
      levels. Eight patients had a repeat MRI to evaluate for resolution of basal
      ganglia deposits. Patient demography, clinical history, and bloodwork were
      recorded. RESULTS: Five of 6 patients who initially had elevated Mn levels had
      normal levels on follow-up. All patients who had Mn levels measured serially had
      a decrease in levels; the mean percent decrease of Mn was 38.1% (range, 10.1%
      53.8%). Two patients had elevated Mn despite the absence of supplementation. Six
      of 8 patients who had repeat MRIs had complete resolution abnormalities.
      CONCLUSIONS: Removal of Mn as an additive in HPN solutions resulted in resolution
      of MRI abnormalities in most patients. Over 5 years, all patients except for 1
      maintained normal blood Mn levels. Therefore, Mn levels should be monitored and
      supplementation be individualized.

PMID- 29187041
TI  - Restrictive Cardiomyopathy or Constrictive Pericarditis: An Unresolved Conundrum.
AB  - Cardiomyopathy may have a variety of causes and may lead to significant
      morbidity. Often, there is no "perfect" treatment. New investigative techniques
      may add insight but retain the possibility of uncertainty. The distinction
      between restrictive cardiomyopathy and pericardial constriction may be
      challenging, particularly when considering the incidence of these entities. This
      distinction may significantly impact patient management and this is becoming
      increasingly important in the context of donor organ austerity. We present a case
      of a 17-year-old male to illustrate the overlap highlighting this debate and our
      subsequent management.

PMID- 29187043
TI  - An Atypical Presentation of Alagille Syndrome.
AB  - Alagille syndrome is a multisystem disorder classically involving the liver,
      heart, vertebrae, facial features, and the eyes. In this case report, we document
      a case of Alagille syndrome with an atypical clinical and histopathologic
      presentation and subsequent identification of a novel JAG1 missense mutation.
      This case highlights that there may be both atypical clinical and pathologic
      findings in mutation-proven Alagille syndrome and that the diagnosis of Alagille
      syndrome should be considered in cases of ongoing bile duct damage in the setting
      of early-onset jaundice, cholestasis, hepatosplenomegaly, posterior embryotoxon
      in the eyes, and butterfly vertebrae.

PMID- 29187044
TI  - Smooth time-dependent receiver operating characteristic curve estimators.
AB  - The receiver operating characteristic curve is a popular graphical method often
      used to study the diagnostic capacity of continuous (bio)markers. When the
      considered outcome is a time-dependent variable, two main extensions have been
      proposed: the cumulative/dynamic receiver operating characteristic curve and the
      incident/dynamic receiver operating characteristic curve. In both cases, the main
      problem for developing appropriate estimators is the estimation of the joint
      distribution of the variables time-to-event and marker. As usual, different
      approximations lead to different estimators. In this article, the authors explore
      the use of a bivariate kernel density estimator which accounts for censored
      observations in the sample and produces smooth estimators of the time-dependent
      receiver operating characteristic curves. The performance of the resulting
      cumulative/dynamic and incident/dynamic receiver operating characteristic curves
      is studied by means of Monte Carlo simulations. Additionally, the influence of
      the choice of the required smoothing parameters is explored. Finally, two real
      applications are considered. An R package is also provided as a complement to
      this article.

PMID- 29187045
TI  - Terminal Deoxynucleotidyl Transferase (TdT)-negative Lymphoblastic Leukemia in
      Pediatric Patients: Incidence and Clinical Significance.
AB  - Pediatric terminal deoxynucleotidyl tranferase (TdT)-negative precursor B- or T
      lymphoblastic leukemia/lymphoma (B-LL and T-LL) cases are rare and their
      prognostic significance remains controversial. We aimed to determine the
      frequency of TdT-negative B- and T-LL in the community hospital setting. Between
      2005 and 2015, 43 pediatric patients were diagnosed with lymphoblastic leukemia
      at our institution, of which 6 (14%) were characterized as TdT-negative by flow
      cytometric analysis. Four of these 6 patients had B-LL and the other 2 had T-LL.
      Two of the 6 TdT-negative patients also had undetectable CD34 expression by flow
      cytometry (TdT/CD34 double-negatives). Subsequent paraffin immunohistochemistry
      confirmed the negative CD34 expression in both cases. By contrast, all the 6
      patients had weak TdT-like immunoreactivity in their marrow despite the negative
      flow cytometric analysis. Furthermore, neither TdT/CD34-negative cases showed myc
      rearrangement by fluorescent in situ hybridization, ruling out Burkitt leukemia
      as a differential diagnostic consideration. We conclude that TdT-negative
      pediatric B- and T-LL cases (especially those that are TdT/CD34 double-negative)
      may pose diagnostic challenge to hematopathologists, and ancillary studies
      (paraffin immunohistochemistry to detect TdT and fluorescent in situ
      hybridization to exclude myc rearrangement) may be instrumental in reaching the
      correct diagnosis.

PMID- 29187046
TI  - Denosumab Improves Bone Mineral Density in Patients With Intestinal Failure
      Receiving Home Parenteral Nutrition: Results From a Randomized, Controlled
      Clinical Trial.
AB  - AIM: Low bone mineral density (BMD) is commonly reported in patients receiving
      home parenteral nutrition (HPN). Oral and intravenous calcium, vitamin D, and
      bisphosphonates have been used to treat BMD but with low efficiency due to their
      limited absorption and patient compliance. Denosumab is a new drug that helps
      prevent osteoclast development and activation and led to decreased bone
      resorption in some studies. The aim of this study was to assess its value in HPN
      patients. METHODS: Between November 2011 and March 2013, 49 patients receiving
      HPN (29 women, 20 men, mean age 55.3 years) who met the eligibility criteria were
      randomly assigned to a denosumab or control group. Regional dual-energy x-ray
      absorptiometry of the spine and hip was performed before therapy and after 12
      months. BMD, T score, and z score were assessed. RESULTS: Fifteen patients
      received 2 doses of therapy and were fully reassessed after 1 year. At baseline
      and after 12 months, the absorptiometry revealed T scores of -3.439 standard
      deviations (SD) vs -2.33 SD at lumbar segment 2 (L2) and -2.957 SD vs -2.067 SD
      at lumbar segment 3 (L3), z scores of -2.24 SD vs -1.36 SD at L2 and -1.995 vs 
      1.067 SD at L3, and BMD of 0.801 vs 0.946 at L2 and 0.857 vs 0.979 at L3,
      respectively. Two serious outcomes were reported, without any correlation to the
      intervention. Two patients were weaned off HPN and hence discontinued. One
      patient experienced sciatica, resulting in discontinuation of the intervention.
      CONCLUSIONS: This study showed that denosumab may be a valuable treatment option
      for improving BMD in HPN patients.

PMID- 29187047
TI  - Defining and Using Preoperative Predictors of Diabetic Remission Following
      Bariatric Surgery.
AB  - BACKGROUND: Diabetes remission is defined as the return of glycemic control in
      the absence of medication or insulin use after bariatric surgery. We sought to
      identify and assess the clinical utility of a predictive model for remission of
      type 2 diabetes mellitus in a population seeking bariatric surgery. METHOD: A
      retrospective cohort design was applied to presurgical data on patients referred
      for Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG). The
      model developed from logistic regression was compared with a published model
      through receiver operating characteristic analyses. RESULTS: At 12 months
      postoperatively, 59.7% of the cohort was remitted, with no differences between
      RYGB and VSG. Logistic regression analyses yielded a model in which 4
      preoperative variables reliably predicted remission. A Hosmer-Lemeshow goodness
      of-fit test result of 0.204 indicated good fit of the developed prediction model
      to our outcome data. The predictive accuracy of this prediction model was
      compared with a published model, and an associated variation with diabetes years
      was substituted for age in our patient population. Our model was the most
      accurate. CONCLUSIONS: Using these predictors, healthcare providers may be able
      to better counsel patients who are living with diabetes and considering bariatric
      surgery on the likelihood of achieving remission from the intervention. This
      refined prediction model requires further testing in a larger sample to evaluate
      its external validity.

PMID- 29187048
TI  - Multitargeted Feeding Strategies Improve Nutrition Outcome and Are Associated
      With Reduced Pneumonia in a Level 1 Trauma Intensive Care Unit.
AB  - BACKGROUND: Factors impeding delivery of adequate enteral nutrition (EN) to
      trauma patients include delayed EN initiation, frequent surgeries and procedures,
      and postoperative ileus. We employed 3 feeding strategies to optimize EN
      delivery: (1) early EN initiation, (2) preoperative no nil per os feeding
      protocol, and (3) a catch-up feeding protocol. This study compared nutrition
      adequacy and clinical outcomes before and after implementation of these feeding
      strategies. METHODS: All trauma patients aged >=18 years requiring mechanical
      ventilation for >=7 days and receiving EN were included. Patients who sustained
      nonsurvivable injuries, received parenteral nutrition, or were readmitted to the
      intensive care unit (ICU) were excluded. EN data were collected until patients
      received an oral diet or were discharged from the ICU. The improvement was
      quantified by comparing nutrition adequacy and outcomes between April 2014-May
      2015 (intervention) and May 2012-June 2013 (baseline). RESULTS: The intervention
      group (n = 118) received significantly more calories (94% vs 75%, P < .001) and
      protein (104% vs 74%, P < .001) than the baseline group (n = 121). The percentage
      of patients receiving EN within 24 and 48 hours of ICU admission increased from
      41% to 70% and from 79% to 96% respectively after intervention ( P < .001).
      Although there were fewer 28-day ventilator-free days in the intervention group
      than in the baseline group (12 vs 16 days, P = .03), receipt of the intervention
      was associated with a significant reduction in pneumonia (odds ratio, 0.53; 95%
      confidence interval, 0.31-0.89; P = .017) after adjusting sex and Injury Severity
      Score. CONCLUSIONS: Implementation of multitargeted feeding strategies resulted
      in a significant increase in nutrition adequacy and a significant reduction in
      pneumonia.

PMID- 29187050
TI  - Influence of Dietitians in Preventing Parenteral Nutrition Prescription Errors in
      Children.
AB  - BACKGROUND: The purpose of this study is to determine whether direct involvement
      by dietitians in parenteral nutrition (PN) ordering resulted in a reduction in PN
      prescriptions errors. METHODS: A prospective audit of PN prescriptions was
      undertaken at a pediatric hospital over 50 weeks. Prescriptions for PN that had
      dietitian involvement (dietitian group) were compared with prescriptions in which
      dietitians were not directly involved (nondietitian group). The number of total
      prescriptions, the number of prescriptions with errors, and the types of errors
      from both groups were recorded. Errors were classified into "dietitian
      preventable errors" and "nondietitian-preventable errors." Comparisons were made
      between prescriptions with and without errors, between dietitian-preventable and
      nondietitian-preventable errors, and between the dietitian and nondietitian
      groups per error type. RESULTS: The total number of PN prescriptions was 725
      (from 45 patients) and 471 (from 66 patients) for the dietitian and nondietitian
      groups, respectively. The nondietitian group was more likely than the dietitian
      group to prescribe PN incorrectly-18.0% (85 of 471) versus 12.4% (90 of 725; P =
      .007)-with the nondietitian group having 1.5-times more PN prescriptions with
      errors (risk ratio = 1.5, 95% CI: 1.1-1.9). The total number of prescription
      errors was 126 and 146 for the dietitian and nondietitian groups, respectively.
      The dietitian group was less likely than the nondietitian group to be associated
      with dietitian-preventable errors: 65.9% (83 of 126) versus 87.0% (127 of 146;
      risk ratio = 1.3, 95% CI: 1.1-1.5; P < .0001). CONCLUSION: Dietitian input into
      prescription of PN reduced the number of prescriptions with errors.

PMID- 29187051
TI  - The New European Society for Clinical Nutrition and Metabolism Definition of
      Malnutrition: Application for Nutrition Assessment and Prediction of
      Morbimortality in an Emergency Service.
AB  - BACKGROUND: Recently, the European Society for Clinical Nutrition and Metabolism
      (ESPEN) provided novel consensus criteria for malnutrition diagnosis. This study
      aimed to evaluate the applicability of this instrument in combination with
      different nutrition screening tools (1) to identify malnutrition and (2) to
      predict morbidity and mortality in hospitalized patients. MATERIALS AND METHODS:
      Observational prospective study in 750 adults admitted to the emergency service
      of a tertiary public hospital. Subjective Global Assessment (SGA-reference
      method) and the new ESPEN criteria were used to assess nutrition status of
      patients, who were initially screened for nutrition risk using 4 different tools.
      Outcome measures included length of hospital stay, occurrence of infection, and
      incidence of death during hospitalization, analyzed by logistic regression.
      RESULTS: There was a lack of agreement between the SGA and ESPEN definition of
      malnutrition, regardless of the nutrition screening tool applied previously
      (kappa = -0.050 to 0.09). However, when Malnutrition Screening Tool and
      Nutritional Risk Screening-2002 (NRS-2002) were used as the screening tool,
      malnourished patients according to ESPEN criteria showed higher probability of
      infection (relative risk [RR], 1.54; 95% confidence interval [CI], 1.02-2.31 and
      RR, 2.06; 95% CI, 1.37-3.10, respectively), and when the NRS-2002 was used, the
      risk for death was 2.7 times higher (hazard ratio, 2.69; 95% CI, 1.07-6.81) in
      malnourished patients than in well-nourished patients. CONCLUSION: Although the
      new ESPEN criteria had a poor diagnostic value, it seems to be a prognostic tool
      among hospitalized patients, especially when used in combination with the NRS
      2002.

PMID- 29187053
TI  - Applying a health literacy lens to youth sport: a focus on doping prevention in
      Germany.
AB  - There are two camps when it comes to youth in high-performance sports and whether
      competition is good or destructive. Despite opportunities for positive
      development, the demands of increasing competitive levels and related situational
      stressors among young athletes can be a double-edged sword. Doping is becoming
      increasingly popular and more readily available to the youth sports population.
      Improving the health of youth in competitive sport requires us to think about
      health and its determinants in a more sophisticated manner. We share a current
      initiative in Germany that reflects this broader thinking by integrating
      'education for health literacy' as one strategy in youth sport settings with
      regard to doping prevention. Implications and emerging opportunities to take
      further action for doping prevention and health improvement applicable for German
      and global contexts are offered.

PMID- 29187052
TI  - Mesenchymal Stem Cell Therapy Prevents Abortion in CBA/J * DBA/2 Mating.
AB  - Immunological disorders are among the main causes of recurrent spontaneous
      abortions (RSAs). Mesenchymal stem cells (MSCs) have been shown to modulate
      various aspects of immune responses. It seems that MSCs may improve the
      immunological conditions in immune-mediated RSA. The aim of this study is the
      reduction of resorption in RSA mouse model through MSCs therapy. The adipose
      derived MSCs were administered intraperitoneal to pregnant CBA/J mice on day 4.5
      of gestation in abortion-prone matting. On day 13.5 of pregnancy, abortion rates
      were calculated and transforming growth factor-beta (TGF-beta), interleukin 10
      (IL-10), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF
      alpha) gene expression in deciduas were evaluated by real-time polymerase chain
      reaction (PCR). The level of TGF-beta in serum was also determined by enzyme
      linked immunosorbent assay (ELISA) method. The obtained results showed that MSCs
      therapy could reduce the abortion rate significantly in test group compared to
      controls. MSCs therapy also caused a significant upregulation of TGF-beta and IL
      10 and downregulation of IFN-gamma and TNF-alpha genes expression in deciduas.
      However, the levels of TGF-beta didn't change in mice sera. Due to the
      significant decrease in abortion rate, we concluded that MSCs therapy could
      modulate the immune responses in fetomaternal interface and protect fetus from
      undesirable immune responses. So, these cells might be considered as a new
      therapeutic for spontaneous pregnancy loss. The local upregulation of TGF-beta
      and IL-10 and downregulation of IFN-gamma and TNF-alpha gene expression in
      decidua could be considered as one possible mechanism of immune regulation, which
      could protect the fetus.

PMID- 29187059
TI  - Bridging observational studies and randomized experiments by embedding the former
      in the latter.
AB  - Consider a statistical analysis that draws causal inferences from an
      observational dataset, inferences that are presented as being valid in the
      standard frequentist senses; i.e. the analysis produces: (1) consistent point
      estimates, (2) valid p-values, valid in the sense of rejecting true null
      hypotheses at the nominal level or less often, and/or (3) confidence intervals,
      which are presented as having at least their nominal coverage for their
      estimands. For the hypothetical validity of these statements, the analysis must
      embed the observational study in a hypothetical randomized experiment that
      created the observed data, or a subset of that hypothetical randomized data set.
      This multistage effort with thought-provoking tasks involves: (1) a purely
      conceptual stage that precisely formulate the causal question in terms of a
      hypothetical randomized experiment where the exposure is assigned to units; (2) a
      design stage that approximates a randomized experiment before any outcome data
      are observed, (3) a statistical analysis stage comparing the outcomes of interest
      in the exposed and non-exposed units of the hypothetical randomized experiment,
      and (4) a summary stage providing conclusions about statistical evidence for the
      sizes of possible causal effects. Stages 2 and 3 may rely on modern computing to
      implement the effort, whereas Stage 1 demands careful scientific argumentation to
      make the embedding plausible to scientific readers of the proffered statistical
      analysis. Otherwise, the resulting analysis is vulnerable to criticism for being
      simply a presentation of scientifically meaningless arithmetic calculations. The
      conceptually most demanding tasks are often the most scientifically interesting
      to the dedicated researcher and readers of the resulting statistical analyses.
      This perspective is rarely implemented with any rigor, for example, completely
      eschewing the first stage. We illustrate our approach using an example examining
      the effect of parental smoking on children's lung function collected in families
      living in East Boston in the 1970s.

PMID- 29187060
TI  - Inflammation and atherosclerosis: fulfilling Koch's postulates.

PMID- 29187061
TI  - Accuracy of Predictive Equations for Energy Expenditure in Mexicans Living With
      HIV/AIDS With and Without Antiretroviral Therapy.
AB  - INTRODUCTION: Determination of the resting energy expenditure (REE) is essential
      for planning nutrition therapy in patients with human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome (AIDS) to help to improve their
      nutrition status. We aim to evaluate the agreement and accuracy of prediction
      equations that estimate the REE in a Mexican population with a diagnosis of
      HIV/AIDS with and without antiretroviral therapy (ART). METHODS: A cross
      sectional study in Mexican patients with HIV/AIDS with and without ART. Weight,
      height, and body composition measured with dual-energy x-ray absorptiometry were
      evaluated. The REE was determined with indirect calorimetry and estimated using
      the Mifflin-St Jeor (MSJ), Harris-Benedict (HB), Schofield 1 and 2, Cunningham,
      Melchior 91, Melchior 93, and Batterham equations. The Bland-Altman method
      assessed agreement between the real and estimated values, and the percent
      difference between these values was used to assess the prediction accuracy.
      RESULTS: Sixty-five adults without ART and 102 adults with ART were included. The
      mean REE (kcal/kg) was 24.8 +/- 2.4 and 23.8 +/- 3.6 in patients without and with
      ART, respectively. Good agreement and reliability were observed in the HB
      (intraclass correlation coefficient [ICC], 0.75; P < .05), Batterham (ICC, 0.79;
      P < .05), Schofield 1 (ICC, 0.74; P < .05), and Schofield 2 (ICC, 0.78; P < .05)
      results in individuals without ART. In individuals with ART, good agreement and
      reliability were observed with the HB equation (ICC, 0.76; P < .05). The MSJ
      equation showed good agreement with poor reliability (ICC, 0.05; P < .05).
      CONCLUSION: The equations with the best agreement and accuracy were Schofield 2,
      Batterham, and HB in individuals without ART and HB and MSJ in the population
      with ART.

PMID- 29187062
TI  - Marginal versus conditional beta-binomial regression models.

PMID- 29187063
TI  - Nutrition Deficiencies in Children With Intestinal Failure Receiving Chronic
      Parenteral Nutrition.
AB  - BACKGROUND: Home parenteral nutrition (PN) is a lifesaving therapy for children
      with intestinal failure (IF). Our aims were to describe the prevalence of
      micronutrient deficiencies (vitamin D, zinc, copper, iron, selenium) in a diverse
      population of children with IF receiving PN and to identify and characterize risk
      factors associated with micronutrient deficiencies, including hematologic
      abnormalities. METHODS: Data were collected on 60 eligible patients through
      retrospective chart review between May 2012 and February 2015. Descriptive
      statistics included frequencies, medians, interquartile ranges (IQRs), and odds
      ratios (ORs). Statistical analyses included chi2, Fisher's exact, t tests, and
      logistic, univariate, and multivariate regressions. RESULTS: Patients were
      primarily young (median age, 3.3 years; IQR, 0.7-8.4), Latino (62%), and male
      (56%), with short bowel syndrome (70%). Of 60 study patients, 88% had >=1
      deficiency and 90% were anemic for age. Of 51 patients who had all 5 markers
      checked, 59% had multiple deficiencies (defined as >=3). Multivariate analysis
      shows multiple deficiencies were associated with nonwhite race (OR, 9.4; P =
      .012) and higher body mass index z score (OR, 2.2; P = .016). Children with
      severe anemia (hemoglobin <8.5 g/dL) made up 50% of the cohort. Nonwhite race
      (OR, 6.6; P = .037) and zinc deficiency (OR, 11; P = .003) were multivariate
      predictors of severe anemia. CONCLUSIONS: Micronutrient deficiency and anemia are
      overwhelmingly prevalent in children with IF using chronic PN. This emphasizes
      the importance of universal surveillance and supplementation to potentially
      improve quality of life and developmental outcomes. Future research should
      investigate how racial disparities might contribute to nutrition outcomes for
      children using chronic PN.

PMID- 29187064
TI  - Editorial for the special issue of "Statistical Methods in Medical Research" on
      "Advanced ROC analysis".

PMID- 29187065
TI  - A Systematic Literature Review and Research Agenda for Organ Donation Decision
      Communication.
AB  - BACKGROUND: This study systematically located and appraised peer-reviewed
      evidence for the efficacy of strategies to increase organ donation decision
      communication among adults including an assessment of study quality to guide
      future research in this field. There is little room to move in strengthening
      unanimously positive public attitudes toward organ donation. Consequently,
      researchers have called for a focus on organ donation decision communication to
      understand modifiable factors to increase organ donation rates. METHODS: Multiple
      databases were searched during September 2015, and 44 studies were selected for
      inclusion. Data concerning participants, design, and outcomes were extracted.
      Studies were rated for quality and levels of evidence. FINDINGS: Although not
      amenable to meta-analysis, the literature indicates that approximately 50% of
      adults who are willing to become an organ donor have discussed this decision with
      family. The majority of research was conducted in a Western context with an
      overrepresentation of students. Strategies to increase communication include
      education, motivation, input from lived experience, efforts to address salient
      audience beliefs, and scheduled reminders or prompts. Intentions and willingness
      to discuss organ donation were consistently positively related to discussion
      behavior; however, formative research and experimental studies testing
      theoretically driven interventions were scarce. CONCLUSIONS: There is mixed
      evidence for the role of demographic and attitudinal characteristics in the
      success of organ donation communication interventions. Additional theoretically
      based research is recommended to establish boundary conditions and validate
      strategies to increase organ donation decision communication among adults.

PMID- 29187066
TI  - Pilot-scale sorption studies of diethylketone in the presence of Cd2+ and Ni2.
AB  - The effect of pH on the sorption capacity of vermiculite towards cadmium and
      nickel was tested in batch systems and it was shown that the sorption percentages
      increase with an increase in the mass of vermiculite and with an increase in the
      initial pH. Maximum sorption percentages were obtained for a pH of 8 and 4 g of
      vermiculite (86.5% for Cd2+ and 86.1% for Ni2+, for solutions with 100 mg/L of
      metal). As a consequence, it was possible to establish a range of optimal pH for
      biosorption processes, by combining the so determined optimal sorption pH of
      vermiculite with the optimal growth pH of Streptococcus equisimilis, a bacterium
      used to treat contaminated water. Pilot-scale experiments with a S. equisimilis
      biofilm supported on vermiculite were conducted in closed-loop conditions, aiming
      to treat large volumes of diethylketone aqueous solutions, eventually containing
      Cd2+ or Ni2+. The excellent capacity of this joint system to simultaneously
      biodegrade diethylketone and biosorb Cd2+ or Ni2+was proved. The removal
      percentage and the uptake increase through time, even with the replacement of the
      initial solution by new ones. The breakthrough curves that best describe the
      results achieved for Cd2+ and Ni2+ are respectively the Adams-Bohart and the Yoon
      and Nelson model.

PMID- 29187067
TI  - When people's judgments of learning (JOLs) are extremely accurate at predicting
      subsequent recall: the "Displaced-JOL effect".
AB  - Judgments of learning (JOL) made after a delay more accurately predict subsequent
      recall than JOLs made immediately after learning. One explanation is that delayed
      JOLs involve retrieving information about the target item from secondary memory,
      whereas immediate JOLs involve retrieval from primary memory. One view of working
      memory claims that information in primary memory is displaced to secondary memory
      when attention is shifted to a secondary task. Thus, immediate JOLs might be as
      accurate as delayed JOLs if an intervening task displaces the target item from
      primary memory, requiring retrieval from secondary memory, prior to making the
      JOL. In four experiments, participants saw related word-pairs and made JOLs
      predicting later recall of the item. In Experiment 1, delayed JOLs were more
      accurate than JOLs made shortly after learning, regardless of whether a secondary
      task intervened between learning and JOL. In Experiments 2-4, the secondary task
      demands increased and JOLs made shortly after learning with an intervening task
      were just as accurate as delayed JOLs, and both were more accurate than immediate
      JOLs with no intervening task (Experiment 4). These results are consistent with a
      retrieval-based account of JOLs, and demonstrate that the "delayed-JOL effect"
      can be obtained without a long delay.

PMID- 29187068
TI  - Environmental and economic benefits of the recovery of materials in a municipal
      solid waste management system.
AB  - The main aim of this study was to perform a Life cycle assessment study as well
      as an economic evaluation of the recovery of recyclable materials in a municipal
      solid waste management system. If citizens separate erroneously waste fractions,
      they produce both environmental and economic damages. The environmental and
      economic evaluation was performed for the case study of Nola (34.349 inhabitants)
      in Southern Italy, with a kerbside system that assured a source separation of 62%
      in 2014. The economic analysis provided a quantification of the economic benefits
      obtainable for the population in function of the achievable percentage of source
      separation. The comparison among the environmental performance of four considered
      scenarios showed that the higher the level of source separation was, the lower
      the overall impacts were. This occurred because, even if the impacts of the waste
      collection and transport increased, they were overcome by the avoided impacts of
      the recycling processes. Increasing the source separation by 1% could avoid the
      emission of 5 kg CO2 eq. and 5 g PM10 for each single citizen. The economic and
      environmental indicators defined in this study provide simple and effective
      information useful for a wide-ranging audience in a behavioural change programme
      perspective.

PMID- 29187069
TI  - Development of alpha- and gamma-Fe2O3 decorated graphene oxides for glyphosate
      removal from water.
AB  - In this study, the proposed adsorbent composed of graphene oxide (GO)
      functionalized by magnetic nanoparticles of iron oxide (alpha-gamma-Fe2O3) was
      obtained by a simple ultrasonication process. This new material was used for the
      removal of glyphosate in water. The nanoparticulated iron oxide used was
      synthesized by means of a modified sol-gel method, which does not use organic
      solvents. The adsorbent material (GO-alpha-gamma-Fe2O3) obtained was
      characterized by magnetic measurements, and it can be proved that it has
      superparamagnetic properties, allowing fast and efficient magnetic separation.
      The equilibrium time for the adsorption of glyphosate when using GO-alpha-gamma
      Fe2O3 was 2 hours and the maximum removal was 92% at 15 degrees C, with a maximum
      adsorption capacity of 46.8 mg g-1. Langmuir model and pseudo-second-order
      kinetic model correlated satisfactorily to the experimental data. The
      thermodynamic parameters showed that the adsorption of glyphosate on GO-alpha
      gamma-Fe2O3 was spontaneous, exothermic and thermodynamically favorable at
      temperature of 15-45 degrees C. Thus the adsorbent material GO-alpha-gamma-Fe2O3
      proposed in this study is considered a good candidate to be used in the removal
      of glyphosate from aqueous solutions, presenting high adsorption capacity, low
      cost and magnetic properties that facilitate the separation of the adsorbent
      material.

PMID- 29187070
TI  - Loading efficacy and binding analysis of retinoids with milk proteins: a short
      review.
AB  - In this review, the loading efficacies of retinoids with milk proteins are
      investigated. It has been shown that milk proteins beta-lactoglobulin, alpha-,
      and beta-caseins bind retinol and retinoic acid via hydrophobic, hydrophilic, and
      H-bonding contacts causing minor alterations of protein secondary structure.
      Hydrophobic contact is predominant in retinoid-protein conjugation and several
      amino acids are involved in complex formation, stabilized by H-bonding network.
      Loading efficacy of retinoid was about 30-50% with retinol forming more stable
      protein conjugates. Milk proteins can transport retinoid to target molecules.

PMID- 29187071
TI  - Endovascular Stent Can Be the Treatment of Choice for Spontaneous Iliac Vein
      Rupture: A Case Report.
AB  - INTRODUCTION: Spontaneous iliac vein rupture is a rare but lethal disease. Most
      patients suffer from shock status in the emergency department. Until now, open
      laparotomy combined with primary suture is the most common treatment of iliac
      vein rupture. However, there is high mortality and morbidity in the patients who
      underwent open laparotomy. CASE PRESENTATION: A 71-year-old woman denied trauma
      history and sustained hypovolemic shock. The abdominal computed tomography showed
      one huge retroperitoneal hematoma. The emergency angiography revealed one obvious
      rupture point on the left external iliac vein. We repaired the lesion with
      endovascular stent and open laparotomy for abdominal decompression. The patient
      progressed well and was discharged. CONCLUSION: Endovascular repair is an
      effective and safe treatment. Compared with open laparotomy and primary suture,
      stent leads to fewer complications and a lower mortality rate.

PMID- 29187072
TI  - Understanding the growth of the bio-struvite production Brevibacterium antiquum
      in sludge liquors.
AB  - Biological struvite (bio-struvite) production through biomineralization has been
      suggested as an alternative to chemically derived struvite production to recover
      phosphorus from wastewater streams. In this study, statistical experimental
      design techniques were used to find the optimal growth rate (MU) of
      Brevibacterium antiquum in sludge liquors. Acetate, oleic acid, NaCl, NH4-N, and
      Ca2+ were shown to affect the growth rate of B. antiquum. The growth rate reached
      3.44 1/d when the bacteria were supplemented with 3.0% w/v NaCl and 1124 mg
      chemical oxygen demand/L as acetate. However, NaCl was found to hinder the
      biomineralization of bio-struvite. A two-stage experiment demonstrated that bio
      struvite was produced in the presence of acetate. Bio-struvite production was
      confirmed with X-ray spectroscopy and crystal morphology (prismatic, tabular, and
      twinned crystal habit) through electron microscope analysis. The bio-struvite
      production was estimated by measuring phosphate content of the recovered
      precipitates, reaching 9.6 mg P/L as bio-struvite. Overall, these results
      demonstrated the optimal conditions required to achieve high growth rates as well
      as bio-struvite production with B. antiquum. The results obtained in this study
      could be used to develop a process to grow B. antiquum in wastewater streams in
      mixed cultures and recover phosphorus-rich products such as struvite.

PMID- 29187073
TI  - Elevation of intracellular calcium and oxidative stress is involved in
      perfluorononanoic acid-induced neurotoxicity.
AB  - Perfluorononanoic acid (PFNA) is one of the major perfluorinated compounds found
      in both biological and abiotic samples and has recently been demonstrated to
      cause neurobehavioral defects in mammals. In this study, pheochromocytoma-12
      (PC12) cells were exposed to various doses of PFNA to explore the cytotoxicity of
      PFNA to neurons and the possible mechanisms underlying these effects. The results
      showed that exposure to PFNA dose-dependently decreased the viability of PC12
      cells and increased the release of lactate dehydrogenase into cell culture media.
      Exposure to PFNA increased the malondialdehyde content and decreased the total
      antioxidant capacity and glutathione peroxidase activity in PC12 cell culture
      supernatants. Exposure to PFNA increased the intracellular calcium level and
      upregulated the Ca2+/calmodulin-dependent protein kinase II (CaMKII) expression
      in PC12 cells. PFNA also decreased Bcl-2 expression and increased Bax expression
      in PC12 cells. These results suggested that exposure to PFNA elevated the
      intracellular calcium level and activated the CaMKII signaling pathway, which may
      aggravate oxidative stress in PC12 cells and lead to cell damage or cell
      apoptosis.

PMID- 29187074
TI  - Long-term dynamics of the bacterial community in a Swedish full-scale wastewater
      treatment plant.
AB  - The operational efficiency of activated sludge wastewater treatment plants
      depends to a large extent on the microbial community structure of the activated
      sludge. The aims of this paper are to describe the composition of the bacterial
      community in a Swedish full-scale activated sludge wastewater treatment plant, to
      describe the dynamics of the community and to elucidate possible causes for
      bacterial community composition changes. The bacterial community composition in
      the activated sludge was described using 16S rRNA gene libraries and monitored
      for 15 months by a terminal restriction fragment (T-RF) length polymorphism (T
      RFLP) analysis of the 16S rRNA gene. Despite variable environmental conditions, a
      large fraction of the observed T-RFs were present at all times, making up at
      least 50% in all samples, possibly representing a relatively stable core fraction
      of the bacterial community. However, the proportions of the different T-RFs in
      this fraction as well as the T-RFs in the more variable fraction showed a
      significant variation over time and temperature. The difference in community
      composition between summer and winter coincided with observed differences in floc
      structure. These observations suggest a relationship between floc properties and
      bacterial community composition, although additional experiments are required to
      determine causality.

PMID- 29187075
TI  - Retention in Care among Patients with Early HIV Disease in Haiti.
AB  - In September 2015, the World Health Organization updated their guidelines to
      recommend antiretroviral therapy (ART) for all people living with HIV. Countries
      are now in the process of implementing strategies to provide universal HIV
      treatment. We analyzed the rate of retention and time to ART eligibility
      (according to 2013 WHO guidelines) among 3,345 adult patients receiving positive
      HIV test results between February 1, 2003 and March 31, 2013 at the GHESKIO
      Clinic in Haiti, with WHO stage 1 or 2 disease and initial CD4 cell count >500
      cells/mm3. Among the 3,345 patients, 2,423 (72%) were female, the median age was
      33 years, 3,089 (92%) lived in Port-au-Prince, and 1,944 (58%) had attended no
      school or primary school only. The median initial CD4 cell count was 668
      cells/mm3 (IQR: 572-834); over the subsequent 2 years, 1,485 patients (44%) were
      lost to follow-up and 7 (<1%) died pre-ART, 1,041 (31%) were retained in pre-ART
      care, and 819 (24%) initiated ART. In multivariate analysis, secondary education
      (aOR 1.27; 95% CI: 1.10-1.47), female gender (aOR: 1.28; 95% CI: 1.09-1.50), co
      habitation (aOR: 1.31; 95% CI: 1.09-1.57), and residence in Port-au-Prince (aOR:
      1.43; 95% CI: 1.09-1.88) were associated with retention in care. The median time
      from baseline CD4 count to ART eligibility was 1.7 years. Prior to the
      implementation of universal treatment, pre-ART attrition was high among patients
      who did not qualify for ART at presentation. Though implementing WHO
      recommendations for universal ART will require service expansion, it will likely
      result in improved retention for those at risk of being lost to follow-up.

PMID- 29187076
TI  - Clinicoepidemiological Profile of Elderly PLHIV Attending a Tertiary Care Center
      in South India.
AB  - BACKGROUND: Physicians are coming across a considerable number of HIV-positive
      patients belonging to older age-group, in practice. They pose a challenge as they
      might present with advanced forms and comorbid conditions. We aimed to describe
      the clinicoepidemiological profile of elderly people living with HIV.
      METHODOLOGY: We conducted a cross-sectional study at Kasturba Medical College,
      Mangalore. We analyzed the record of 120 patients from 2009 to 2014. Descriptive
      statistics were used to describe sociodemographic and clinical profile of
      patients. RESULTS: Of 786 HIV-positive patients, 120 were elderly. Mean age was
      55.9 +/- 6.1 years. Majority 68% were male. In all, 63.33% were male. Commonest
      route of transmission was heterosexual intercourse, most presented at World
      Health Organization (WHO) stage 1 (64.17%). In all, 77.5% had hypertension and
      26.6% had tuberculosis. The median CD4 count at presentation was 245 cells/mm3
      (145-426 cells/mm3). Forty-two percent were late presenters (CD4 <200 cells/mm3).
      CONCLUSION: Treating physician should have a high index of suspicion in
      diagnosing HIV among elderly age-group.

PMID- 29187078
TI  - Maternal fluoride exposure during gestation and lactation decreased learning and
      memory ability, and glutamate receptor mRNA expressions of mouse pups.
AB  - Previous investigations demonstrated that high fluoride (F) exposure may
      adversely affect the neurodevelopment and learning and memory ability. However,
      whether maternal F exposure during gestation and lactation can influence the
      learning, memory ability, and glutamate receptor expressions of offspring has not
      yet been elucidated. Hence, in the present study, maternal mice were exposed to F
      (25, 50, or 100 mg/L sodium fluoride (NaF) in drinking water) during gestation
      and lactation. Results showed that exposure to 100 mg/L NaF significantly
      enhanced the number of total arm entries and working memory errors of offspring
      in the radial arm maze test compared to the control group. However, no difference
      was observed in open-field behaviors. For the subtypes of glutamate receptors in
      hippocampus, expression of GluR2 mRNA was significantly reduced by 25, 50, and
      100 mg/L NaF. Besides, F exposure also suppressed the expression of NR2A, NR2B,
      and mGluR2 mRNA levels in a dose-dependent manner, where NR2A was significantly
      suppressed by 50 mg/L NaF and NR2B and mGluR2 by 100 mg/L NaF. However, no
      significant changes were observed in GluR1 and mGluR5 mRNA expression levels.
      Collectively, these findings suggested that F can pass through the cord blood and
      breast milk and may have deleterious impact on learning and memory of the mouse
      pups, which was mediated by reduced mRNA expression of glutamate receptor
      subunits.

PMID- 29187077
TI  - HIV-Related Knowledge among PLWHA Attending a Tertiary Care Hospital at Coastal
      South India-A Facility-Based Study.
AB  - BACKGROUND: Adequate knowledge about HIV/AIDS among people living with HIV
      (PLHIV) is essential for the prevention of HIV transmission. METHODS: A cross
      sectional study consisting of 409 PLHIV aged >=18 years were interviewed
      regarding their HIV-related knowledge, from April 2014 to April 2015. HIV-related
      knowledge was assessed using the HIV knowledge questionnaire 18 . Univariate and
      multivariate analyses were done to determine the factors associated with high HIV
      related knowledge. Odds ratios with its corresponding 95% confidence intervals
      were reported. A value of P < .05 was considered to be statistically significant.
      RESULTS: Among 409 PLHIV, 46.2% had high HIV-related knowledge. Univariate
      analysis yields factors like upper socioeconomic status, those who are literates,
      unemployed, and adherent to antiretroviral therapy (ART) were associated with
      higher HIV-related knowledge. On multivariate analysis, upper socioeconomic
      status and adherence to ART were the factors that remained significantly
      associated with higher HIV-related knowledge. CONCLUSION: HIV-related knowledge
      among PLHIV can be improved through HIV educational programs.

PMID- 29187079
TI  - Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic
      acid-induced ulcerative colitis.
AB  - : Ulcerative colitis (UC) is a chronic inflammatory disease affecting colon. The
      primary symptoms of UC are diarrhoea with blood and mucus and sometimes
      associated with pain. AIM: This study aimed to evaluate the effects of diosmin
      (DIO) on UC. METHODS: UC was induced in rats by rectal administration of acetic
      acid (AA). The degree of mucosal ulceration and damage was determined by
      evaluating the disease activity index (DAI) and colon damage index scores.
      Inflammation, oxidative stress and apoptotic responses were determined by
      measuring the levels of tumour necrosis factor-alpha (TNF-alpha), cyclooxygenase
      2 (COX-II), malondialdehyde (MDA) and reduced glutathione (GSH) in addition to
      myeloperoxidase (MPO) activity and caspase-3 expression. RESULTS: The results of
      this study indicate that AA caused increase in DAI and colon damage index scores.
      Also, markers of inflammation (TNF-alpha, COX-II and MPO) and oxidative stress
      (MDA and reduced GSH) were significantly elevated. These changes were associated
      with increases in colon caspase-3 expression. Treatment of rats with two doses of
      DIO produced a dose-dependent decline in DAI and colon damage index scores. Also,
      DIO resulted in significant reduction of inflammatory and oxidative stress
      markers as well as reduced the expression of caspase-3. CONCLUSION: DIO therapy
      decreased UC development depending on its ability to decreases inflammation,
      oxidative stress and apoptosis in rat colon.

PMID- 29187080
TI  - "Strange animals": hybrid organisations in health care.
AB  - Purpose The purpose of this paper is to critically explore hybrid organisations
      in health care. It examines the broad literature on hybrids focusing on issues of
      perspective, definition, sub-type and level. It then presents the results of the
      literature review of hybrid health care organisations, exploring which
      organisations have been viewed as hybrids, and then examining studies in more
      detail with respect to the research questions. Design/methodology/approach It
      critically explores the literature on hybrid organisations in health care through
      a structured search. Findings It is found that a wide variety of hybrid forms
      exist, but not clear what they combine or how they combine it. However, the level
      of depth from some of these studies is rather limited, with little consensus on
      definition, and relatively few drawing on any explicit conceptual perspective. It
      seems that the wider hybridity literatures have limited influence of studies of
      hybrid health care organisations. Originality/value As far as the authors are
      aware, this paper is the first attempt to critically review the literature on
      hybrid organisations in health care. It is concluded that it is difficult to
      define and explain hybrid health care organisations. Health care hybrids appear
      to be chameleons as they appear to be able to change their form to different
      observers.

PMID- 29187081
TI  - Medical directors' perspectives on strengthening hospital quality and safety.
AB  - Purpose The purpose of this paper is to understand the concerns and factors that
      impact on hospital quality and safety, particularly related to use of performance
      data, within a setting of devolved governance. Design/methodology/approach This
      qualitative study used thematic analysis of interviews with public hospital
      medical directors. For additional context, findings were framed by themes from a
      review of hospital safety and quality in the same jurisdiction. Findings Varying
      approaches and levels of complexity were described about what and how performance
      data are reviewed, prioritised, and quality improvements implemented. Although no
      consistent narrative emerged, facilitators of improvement were suggested relating
      to organisational culture, governance, resources, education, and technologies.
      These hospital-level perspectives articulate with and expand on the system-level
      themes in a state-wide review of hospital safety and quality. Research
      limitations/implications The findings are not generalisable, but point to an
      underlying absence of system-wide agreement on how to perceive, retrieve,
      analyse, prioritise and action hospital performance data. Practical implications
      Lack of electronic medical records and an inefficient incident reporting system
      limits the extent to which performance and incident data can be analysed, linked
      and shared, thus limiting hospital performance improvement, oversight and
      learning. Social implications Variable approaches to quality and safety,
      standards of care, and hospital record keeping and reporting, mean that
      healthcare consumers might expect inconsistency across Victorian hospitals.
      Originality/value The views of medical directors have been little researched.
      This work uses their voice to better understand contextual factors that situate
      and impact on hospital quality and safety towards understanding the mixed
      effectiveness of hospital quality improvement strategies.

PMID- 29187082
TI  - Lean leadership attributes: a systematic review of the literature.
AB  - Purpose Emphasis on quality and reducing costs has led many health-care
      organizations to reconfigure their management, process, and quality control
      infrastructures. Many are lean, a management philosophy with roots in
      manufacturing industries that emphasizes elimination of waste. Successful lean
      implementation requires systemic change and strong leadership. Despite the
      importance of leadership to successful lean implementation, few researchers have
      probed the question of ideal leadership attributes to achieve lean thinking in
      health care. The purpose of this paper is to provide insight into applicable
      attributes for lean leaders in health care. Design/methodology/approach The
      authors systematically reviewed the literature on principles of leadership and,
      using Dombrowski and Mielke's (2013) conceptual model of lean leadership,
      developed a parallel theoretical model for lean leadership in health care.
      Findings This work contributes to the development of a new framework for
      describing leadership attributes within lean management of health care.
      Originality/value The summary of attributes can provide a model for health-care
      leaders to apply lean in their organizations.

PMID- 29187083
TI  - Overcoming counter-knowledge through telemedicine communication technologies.
AB  - Purpose Knowledge acquired from sources of unverified information such as gossip,
      partial truths or lies, in this paper it is termed as "counter-knowledge." The
      purpose of this paper is to explore this topic through an exploration of the
      links between a Hospital-in-the-Home Units (HHUs) learning process (LP), counter
      knowledge, and the utilization of communication technologies. The following two
      questions are addressed: Does the reduction of counter-knowledge result in the
      utilization of communication technologies? Does the development of counter
      knowledge hinder the LP? Design/methodology/approach This paper examines the
      relevance of communication technologies to the exploration and exploitation of
      knowledge for 252 patients of a (HHU) within a Spanish regional hospital. The
      data collected was analyzed using the PLS-Graph. Findings To HHU managers, this
      study offers a set of guidelines to assist in their gaining an understanding of
      the role of counter-knowledge in organizational LPs and the potential
      contribution of communication technologies. Our findings support the proposition
      that the negative effects of counter-knowledge can be mitigated by using
      communication technologies. Originality/value It is argued in this paper that
      counter-knowledge may play a variety of different roles in the implementation of
      LPs. Specifically, the assignment of communication technologies to homecare units
      has given them the means to filter counter-knowledge and prevent users from any
      possible problems caused by such counter-knowledge.

PMID- 29187084
TI  - Do different approaches to clinical governance development and implementation
      make a difference? Findings from Ireland and New Zealand.
AB  - Purpose Clinical governance (CG) is an important foundation for a high-performing
      health care system, with many countries supporting its development. CG policy may
      be developed and implemented nationally, or devolved to a local level, with
      implications for the overall approach to implementation and policy uptake.
      However, it is not known whether one of these two approaches is more effective.
      The purpose of this paper is to probe this question. Its setting is Ireland and
      New Zealand, two broadly comparable countries with similar CG policies. Ireland's
      was nationally led, while New Zealand's was devolved to local districts. This
      leads to the question of whether these different approaches to implementation
      make a difference. Design/methodology/approach Data from surveys of health
      professionals in both countries were used to compare performance with CG
      development. Findings The study showed that Ireland's approach produced a
      slightly better performance, raising questions about the merits of devolving
      responsibility for policy implementation to the local level. Research
      limitations/implications The Irish and New Zealand surveys both had lower-than
      desirable response rates, which is not uncommon for studies of health
      professionals such as this. The low response rates mean the findings may be
      subject to selection bias. Originality/value Despite the importance of the
      question of whether a national or local approach to policy implementation is more
      effective, few studies specifically focus on this, meaning that this study
      provides a new contribution to the topic.

PMID- 29187085
TI  - Caring for Dying Patient and Their Families: The Lived Experiences of Nursing
      Students in Italy.
AB  - BACKGROUND: The literature from recent decades persistently suggests that nurses
      are not adequately trained in caring for the dying. Numerous studies call for
      enhanced education in end-of-life care. OBJECTIVE: To explore student nurses'
      experience of caring for dying persons and their families and how this experience
      was influenced by their undergraduate education, with a view to improving end-of
      life training. METHODS: Narrative interviews were administered to a purposive
      sample of 18 undergraduate students at Turin University's School of Nursing and
      analyzed following Giorgi's qualitative phenomenological methodology. RESULTS:
      The students' accounts featured 4 main themes: emotions and feelings, reactions
      and coping strategies, growth in personal and professional awareness, and the
      professional nursing model. Students reporting positive experience of end-of-life
      care in clinical settings displayed the expected learning outcomes for
      undergraduate nursing education. CONCLUSION: This study's strength lies in the
      fact that it draws on student nurses' lived experience to assess training in end
      of-life care. It confirms the need to invest in targeted end-of-life education
      and support for nursing students.

PMID- 29187086
TI  - Nutrition Management of Home Parenteral Nutrition Among Patients With
      Enterocutaneous Fistula in the Sustain Registry.
AB  - BACKGROUND: Home parenteral nutrition (HPN) is a vital therapy for patients who
      have the diagnosis of enterocutaneous fistula (ECF), yet little is known about
      how these patients are managed. This research compares nutrition management of
      adults with ECF as the indication for HPN therapy to those with other
      indications. METHODS: This is an analysis of data from adult HPN patients in the
      Sustain registry enrolled between August 2011 and February 2014 who have the
      diagnosis of ECF or other indication for HPN who served as the control group.
      Differences between the ECF and control group were assessed by t test, analysis
      of variance, or chi2 as appropriate. RESULTS: There were 141 HPN patients with
      ECF and 632 control patients. Patients with ECF were older (55 vs 50 years, P <
      .001), more frequently had a goal for future surgery (30% vs 15%, P = .010), had
      greater prevalence of overweight/obesity (33% vs 20%, P = .04), and had a lower
      serum albumin (2.98 +/- 0.65 g/dL vs 3.16 +/- 0.66 g/dL, P = .006) than controls.
      The diet order was more frequently nil per os (NPO) in patients with ECF (48% vs
      22%, P < .001), and amino acid content of HPN was greater (111.90 +/- 29.11 vs
      102.06 +/- 27.84, P < .001) than in controls. There were no differences in
      patterns of weight change by ECF or control groups, although underweight patients
      gained, normal-weight patients maintained, and overweight/obese patients lost
      weight and serum albumin increased similarly. CONCLUSIONS: The HPN management of
      patients with ECF is similar to other HPN patients other than greater provision
      of protein, more frequent NPO status, and a goal for future surgery.

PMID- 29187087
TI  - Heart Transplantation as Last Resort Treatment for Relapsing Polychondritis With
      Severe Cardiac Involvement.
AB  - Relapsing polychondritis is a rare multisystem autoimmune disease characterized
      by recurrent inflammation and destruction of different cartilaginous and
      proteoglycan-rich structures like cardiovascular system. We reported a case of
      heart transplantation in a 20-year-old man having a relapsing polychondritis with
      severe multiple cardiovascular involvement. The immunosuppressive treatment used
      to prevent graft rejection allowed to turn out the inflammatory disease. Cardiac
      transplantation may be considered as last resort treatment option in relapsing
      polychondritis with intractable extensive heart lesions.

PMID- 29187088
TI  - European Vignettes in Donation After Circulatory Death.
AB  - Donation after circulatory death (DCD) is increasing in Europe, yet there is
      widespread variability in practice. Insight into actual practice is difficult to
      acquire simply by analyzing protocols and laws from each individual country. For
      this reason, the 3 DCD vignettes in this article have been constructed to outline
      routine and standard DCD practice in the United Kingdom, the Netherlands, and
      Spain. These imagined vignettes reflect a "typical" case, based on the authors'
      extensive experience with DCD but are not real patient cases. They are a resource
      aimed at stimulating discussion regarding European organ donation practice and
      provide a knowledge bank for those wanting to establish a DCD program in their
      country. It is our hope that by providing these vignettes, the wider organ
      donation and transplant community, as well as philosophers and the public, will
      have a better understanding of what DCD really is and what it really isn't.

PMID- 29187089
TI  - Pyridoxine Deficiency After Solid Organ Transplant.
AB  - OBJECTIVE: Pyridoxine is 1 of 8 B vitamins that assist in a variety of essential
      functions including immune functions. The purpose of this study was to assess the
      risk factors associated with low pyridoxine levels in solid organ transplantation
      recipients. DESIGN: The study cohort was divided into 2 groups: (a) patients with
      normal pyridoxine levels or (b) patients with low pyridoxine levels. Dietary
      evaluation and clinical characteristics of all patients, rejection episodes, and
      immunosuppression were collected. Simple descriptive statistics were used to
      analyze the overall cohort. RESULTS: Of the 48 patients, 29 (60%) in the study
      cohort were identified to have low pyridoxine levels. The mean interval between
      transplantation and pyridoxine level check was 910 days (standard deviation [SD]
      456). The mean weight at the time of dietary consultation was 80 kg (SD 20.7).
      More patients in the deficient group received thymoglobulin for rejection
      treatment (56% vs 0%; P = .01) and were thymoglobulin recipients (78% vs 10%;
      odds ratio [OR] = 31.5; 95% confidence interval [CI], 2.35-422.30; P < .01). A
      strong correlation was identified between thymoglobulin treatment for induction
      and a low level of pyridoxine (correlation coefficient R = 0.6, P = .004) and
      between thymoglobulin treatment for rejection and a low pyridoxine level
      (correlation coefficient R = 0.5, P = .05). Based on multivariate logistic
      regression analysis, only thymoglobulin treatment (induction or rejection
      treatment) was significantly associated with low pyridoxine levels (OR = 19.5,
      95% CI, 1.01-375.24; P < .05). CONCLUSIONS: Low levels of pyridoxine appear to be
      relatively common, and thymoglobulin treatments are associated with low
      pyridoxine levels. Prospective studies are needed to confirm and valuate the
      significance of these findings.

PMID- 29187090
TI  - Outcomes of Patients With Familial Transthyretin Amyloidosis After Liver
      Transplantation.
AB  - BACKGROUND: Familial transthyretin amyloidosis is a disease caused by misfolded
      transthyretin aggregates that can impair multiple organ systems. Liver
      transplantation is the first-line treatment for familial transthyretin
      amyloidosis. RESEARCH QUESTION: Our objective is to study outcomes and survival
      among patients with familial transthyretin amyloidosis after transplantation.
      DESIGN: All patients undergoing orthotopic liver transplant for familial
      transthyretin amyloidosis at Mayo Clinic between 1997 and 2012 were reviewed.
      Baseline clinical characteristics, organs transplanted, and posttransplant
      clinical course were assessed. RESULTS: Of the 40 patients, 7 patients had the
      V30M mutation and 33 had other mutations. Nineteen patients received liver only,
      19 liver and heart, and 2 combined liver, heart, and kidney transplants. The 5
      year overall survival was 85% for those receiving multiple organ transplant and
      52% for those receiving liver transplant only ( P = .057). There was no
      difference in overall survival based on mutation (V30M vs other mutations), but
      survival was confounded by varied disease involvement and organs transplanted.
      Those who had early death (<=24 months from liver transplant) had a higher
      incidence of baseline peripheral neuropathy, autonomic neuropathy, lower modified
      BMI, and higher alkaline phosphatase. DISCUSSION: Outcomes of orthotopic liver
      transplant in familial transthyretin amyloidosis are variable due to
      heterogeneity in mutations and patient status at the time of transplant. Familial
      transthyretin amyloidosis can progress, despite liver transplantation. Patients
      receiving combined liver, heart/kidney transplant demonstrated improved survival
      compared to liver transplant alone.

PMID- 29187091
TI  - Patient and Graft Survival Among Sexagenarian and Septuagenarian Renal Transplant
      Recipients and Donors: The Context for Older Recipients.
AB  - Due to the increasing number of patients with end-stage renal disease, there is a
      growing demand for transplants for recipients and donors aged 60 years and older.
      Using data from the Scientific Registry of Transplant Recipients, we performed
      survival analyses and multivariate logistic regression to help guide transplant
      professional decisions regarding the selection of graft type (living vs deceased)
      and donor age (60-69 vs 70+ years) for recipients aged 60 years and older.

PMID- 29187092
TI  - Courage and Character, Leaders and Legends: An Interview With O. H. "Bud"
      Frazier, MD, FACS, FACC.

PMID- 29187093
TI  - A Standardized Framework for Transplant-Specific Competencies for Dietitians.
AB  - Dietitians have extensive training and are considered the experts in medical
      nutrition therapy (MNT). Although dietitian competencies for MNT are well
      established, competencies that account for the expanded roles of dietitians
      working in transplantation have not been developed. These expanded roles require
      a better understanding of transplant processes, regulations, and even the
      business side of transplant, novel concepts to most dietitians. Therefore, we
      proposed a standardized framework of transplant-specific competencies for
      dietitians practicing in transplantation. These competencies can help improve and
      standardize initial and ongoing training for transplant dietitians moving
      forward, ultimately leading to improved patient care for transplant candidates,
      recipients, and donors.

PMID- 29187094
TI  - Organ Donation Registration and Decision-Making Among Current Blood Donors in the
      Netherlands.
AB  - INTRODUCTION: In the Netherlands, there is a constant shortage in donor organs,
      resulting in long waiting lists. The decision to register as organ donor is
      associated with several demographic, cultural, and personal factors. Previous
      research on attitudes and motivations toward blood and organ donations provided
      similar results. RESEARCH QUESTION: The current study investigated demographic,
      cultural, and personal determinants of organ donation registration among current
      Dutch blood donors. DESIGN: We used data from Donor InSight (2012; N = 20 063), a
      cohort study among Dutch blood donors, to test whether age, gender, religious and
      political preferences, donor attitude, and altruism predicted organ donor
      registration among current blood donors. RESULTS: Organ donors were more often
      represented in the blood donor population compared to the general Dutch
      population. Women showed a higher propensity to be registered as organ donor.
      Higher education as well as higher prosocial value orientation, prosocial
      behavior, that is, doing volunteer work, and awareness of need significantly
      associated with being registered as organ donor. Religious denomination
      negatively predicted organ donation registration across all faiths. DISCUSSION:
      Results are discussed in light of cultural context, and possible implications for
      improving information provision and recruitment are mentioned.

PMID- 29187095
TI  - A Systematic Narrative Review of Effects of Community-Based Intervention on Rates
      of Organ Donor Registration.
AB  - BACKGROUND: The demand for organ donation is increasing worldwide. One possible
      way of increasing the pool of potential posthumous donors is to encourage more
      members of the general public to join an organ donor registry. OBJECTIVE: A
      systematic review was conducted to investigate the effectiveness of psychological
      interventions designed to increase the number of individuals in the community who
      register as organ donors. METHODS: PsycINFO and PubMed databases were searched.
      No date limits were set. Randomized and nonrandomized controlled trials exploring
      the effects of community-based interventions on organ donor registration rates
      were included. Methodological quality was assessed using the "Quality Assessment
      Tool for Quantitative Studies." RESULTS: Twenty-four studies met the inclusion
      criteria; 19 studies found a positive intervention effect on registration. Only 8
      studies were assessed as having reasonable methodological robustness. A narrative
      synthesis was conducted. Factors influencing registration rates include providing
      an immediate registration opportunity and using brief interventions to challenge
      misconceptions and concerns about organ donation. DISCUSSION: Community-based
      interventions can be effective at increasing organ donor registrations among the
      general public. Factors that may increase effectiveness include brief
      interventions to address concerns and providing an immediate registration
      opportunity. Particular consideration should be paid to the fidelity of
      intervention delivery. Protocol registration number: CRD42014012975.

PMID- 29187096
TI  - Survey of Living Organ Donors' Experience and Directions for Process Improvement.
AB  - INTRODUCTION: Understanding living organ donors' experience with donation and
      challenges faced during the process is necessary to guide the development of
      effective strategies to maximize donor benefit and increase the number of living
      donors. METHODS: An anonymous self-administered survey, specifically designed for
      this population based on key informant interviews, was mailed to 426 individuals
      who donated a kidney or liver at our institution. Quantitative and qualitative
      methods including open and axial coding were used to analyze donor responses.
      FINDINGS: Of the 141 survey respondents, 94% would encourage others to become
      donors; however, nearly half (44%) thought the donation process could be improved
      and offered numerous suggestions. Five major themes arose: (1) desire for greater
      convenience in testing and scheduling; (2) involvement of previous donors
      throughout the process; (3) education and promotion of donation through social
      media; (4) unanticipated difficulties, specifically pain; and (5) financial
      concerns. DISCUSSION: Donor feedback has been translated into performance
      improvements at our hospital, many of which are applicable to other institutions.
      Population-specific survey development helps to identify vital patient concerns
      and provides valuable feedback to enhance the delivery of care.

PMID- 29187097
TI  - A Department of Motor Vehicle-Based Intervention to Promote Organ Donor
      Registrations in New York State.
AB  - CONTEXT: Examination of efficacy of motor vehicle representative educational
      training and dissemination of promotional materials as a means to promote organ
      donation enrollments in New York State. OBJECTIVE: To increase the number of New
      York State residents who consent to donation through the department of motor
      vehicle transactions during project period. SETTING: County-run motor vehicle
      offices across New York State. PARTICIPANTS: Customers who present to New York
      Department of Motor Vehicle offices and the representative who work at designated
      bureaus. INTERVENTIONS: point-of-decision materials including promotional
      posters, brochures, website, and the motor vehicle representative training
      sessions. MAIN OUTCOME MEASURES: Reasons for enrollment decision,
      knowledge/experience with donation, monthly consent rates, enrollment in state
      organ, and tissue registry. RESULTS: Customers who elected not to register
      reported no reason or uncertainty surrounding enrollment. The representatives
      reported experience with donation, discussion with customers, and need for
      additional education on organ donation. Enrollment cards were mailed to 799
      project staff; counties where offices participated in intervention did not
      indicate significantly higher monthly enrollments when comparing pre- to
      postenrollment rates. CONCLUSIONS: Use of point-of-decision materials and
      enrollment cards proved inexpensive method to register customers with a 3.6%
      return rate. Customers report low (27%) enrollment rate and reticence to consent
      to donation. Educational training sessions with representatives did not yield
      significant enrollment increases when evaluating data at county-level enrollment.

PMID- 29187098
TI  - Significantly Higher Mortality Following Liver Transplantation Among Patients
      Aged 70 Years and Older.
AB  - INTRODUCTION: The age of liver transplantation recipients in the United States is
      steadily increasing. However, the impact of age on liver transplant outcomes has
      demonstrated contradictory results. RESEARCH QUESTIONS: We aim to evaluate the
      impact of age on survival following liver transplantation among US adults.
      DESIGN: Using data from the United Network for Organ Sharing registry, we
      retrospectively evaluated all adults undergoing liver transplantation from 2002
      to 2012 stratified by age (aged 70 years and older vs aged <70 years), presence
      of hepatocellular carcinoma, and hepatitis C virus status. Overall survival was
      evaluated with Kaplan-Meier methods and multivariate Cox proportional hazards
      models. RESULTS: Compared to patients aged <70 years, those aged 70 years and
      older had significantly lower 5-year survival following transplantation among all
      groups analyzed (hepatocellular carcinoma: 59.9% vs 68.6%, P < .01;
      nonhepatocellular carcinoma: 61.2% vs 74.2%, P < .001; hepatitis C: 60.7% vs
      69.0%, P < .01; nonhepatitis C: 62.6% vs 78.5%, P < .001). On multivariate
      regression, patients aged 70 years and older at time of transplantation was
      associated with significantly higher mortality compared to those aged <70 years
      (hazards ratio: 1.67; 95% confidence interval: 1.48-1.87; P < .001). CONCLUSION:
      The age at the time of liver transplantation has continued to increase in the
      United States. However, patients aged 70 years and older had significantly higher
      mortality following liver transplantation. These observations are especially
      important given the aging cohort of patients with chronic liver disease in the
      United States.

PMID- 29187099
TI  - In Memoriam: Gordon K. Danielson (1931-2017).

PMID- 29187101
TI  - Eisenmenger Syndrome Revisited.

PMID- 29187100
TI  - Congenital Heart Defects in Nigerian Children: Preliminary Data From the National
      Pediatric Cardiac Registry.
AB  - BACKGROUND: Congenital heart defects (CHDs) are common birth defects with
      significant impact on morbidity and mortality. We aimed to compare regional
      patterns of CHDs in Nigeria using a registry-based approach. METHODS: Children
      with echocardiography-confirmed CHDs at 17 medical centers across the country
      were enrolled in a pilot National Pediatric Cardiac Registry from January to
      December 2014. RESULTS: A total of 1,296 children (52.9% male; median age 0.9
      years) with CHDs were enrolled. Patients enrolled in Northern Nigeria constituted
      34.6% of the study population and were older compared to those enrolled from
      Southern Nigeria (2.9 +/- 3.6 vs 2.4 +/- 3.5 years; P = .02). Ventricular septal
      defects were significantly more prevalent in the North (37.4%) compared with the
      South (18.5%; P < .0001), while severe CHDs were more prevalent in the South ( P
      = .004). Of the 208 (16.0%) children who received corrective cardiac
      intervention, only 43 (20.7%) of them had the intervention done in country. More
      patients in the South received intervention compared to the North (19.02% vs
      10.5%; P < .0001). CONCLUSION: This is the first prospective, registry-based,
      multicenter study of CHDs in Nigerian children. We demonstrate important
      differences between the Northern and the Southern geographical regions of the
      country in terms of age at diagnosis, type, and severity of lesion as well as
      access to cardiac surgery. The findings demonstrate the utility of a national
      CHDs registry for understanding clinical epidemiology of CHDs in low- and middle
      income countries and its potential to serve as a basis for research and planning.

PMID- 29187102
TI  - Education and Training in Pediatric Cardiac Critical Care.
AB  - Pediatric cardiac critical care is a new and emerging field. There is no
      standardization to the current education provided, and high-quality patient
      outcomes require such standardization. For physicians, this includes fellowship
      training, specific competencies, and a certification process. For advanced
      practice providers, a standardized curriculum as well as a certification process
      is needed. There is evidence that supports a finding that critical care nursing
      experience may have a positive impact on outcomes from pediatric cardiac surgery.
      A rigorous orientation and meaningful continuing education may augment that. For
      all disciplines and levels of expertise, simulation is a useful modality in the
      education in pediatric cardiac critical care.

PMID- 29187103
TI  - Development and Evaluation of a Continuing Education Program for Nursing
      Technicians at a Pediatric Cardiac Intensive Care Unit in a Developing Country.
AB  - BACKGROUND: The nursing profession faces continuous transformations demonstrating
      the importance of professional continuing education to extend knowledge following
      technological development without impairing quality of care. Nursing assistants
      and technicians account for nearly 80% of nursing professionals in Brazil and are
      responsible for uninterrupted patient care. Extensive knowledge improvement is
      needed to achieve excellence in nursing care. The objective was to develop and
      evaluate a continuing education program for nursing technicians at a pediatric
      cardiac intensive care unit (PCICU) using a virtual learning environment entitled
      EDUCATE. METHODS: From July to September 2015, a total of 24 nursing technicians
      working at the PCICU at a children's hospital located in the northwestern region
      of Sao Paulo state (Brazil) fully participated in the continuing education
      program developed in a virtual learning environment using Wix platform, allowing
      access to video classes and pre- and post-training theoretical evaluation
      questionnaires outside the work environment. The evaluation tools recorded
      participants' knowledge evolution, technological difficulties, educational, and
      overall rating. RESULTS: Knowledge development was descriptively presented as
      positive in more than 66.7%. Content and training were considered "excellent" by
      most participants and 90% showed an interest in the use of technological
      resources. Technical difficulties were found and quickly resolved by 40% of
      participants including Internet access, login, and lack of technical expertise.
      CONCLUSION: The continuing education program using a virtual learning environment
      positively contributed to the improvement in theoretical knowledge of nursing
      technicians in PCICU.

PMID- 29187104
TI  - Response to "Thoroughness" Comment.

PMID- 29187105
TI  - Immune Abnormalities in Patients With Single Ventricle Circulation Precede the
      Fontan Procedure.
AB  - BACKGROUND: Immune abnormalities are common in Fontan patients with protein
      losing enteropathy. Limited data exist on immune function of other patients with
      single ventricle circulation. METHODS: This prospective cohort study evaluated
      immunologic characteristics of children with single ventricle circulation from
      neonatal age up to early post-Fontan period. RESULTS: Low leukocyte counts were
      observed in half of the patients prior to bidirectional Glenn and Fontan surgery.
      Total lymphocyte counts were below normal range in 36% to 63% of patients across
      all groups except patients following Fontan procedure who had normal counts.
      Typical lymphocyte subpopulation patterns were (1) high counts of total and
      helper T lymphocytes (CD3+ and CD4+ cells), low B lymphocytes (CD19+ cells), and
      increased CD4/CD8 ratio in neonates and (2) low T lymphocytes (CD3+, CD4+, CD8+
      cells) with high natural killer cells (CD16+) and B lymphocytes (CD19+ cells) in
      other groups. Low preoperative total lymphocyte counts were associated with
      longer intensive care unit stay in patients after bidirectional Glenn and Fontan
      procedure ( P = .03 and P = .01, respectively) and low leukocyte counts with
      higher incidence of pleural effusions and chylothorax after Fontan procedure ( P
      = .005 and P = .002, respectively). CONCLUSIONS: Single ventricle patients
      display several immunological abnormalities. Beyond the neonatal age, an immune
      pattern includes CD3+, CD4+, CD8+ lymphopenia, and CD16+ and CD19+ lymphocytosis.
      B-cell lymphocytosis compensates T-cell lymphopenia, producing normal total
      lymphocyte counts in patients early after Fontan surgery. Low preoperative total
      lymphocyte counts may be associated with longer postoperative intensive care unit
      stay in patients with bidirectional Glenn and Fontan procedure and leukopenia
      with pleural effusions in Fontan patients.

PMID- 29187106
TI  - Comment on "Thoroughness" of Literature Cited by Lugones et al and Overman.

PMID- 29187107
TI  - The Burdens of Offering: Ethical and Practical Considerations.
AB  - We reflect upon highlights of a facilitated panel discussion from the 2016
      Pediatric Cardiac Intensive Care Society Meeting. The session was designed to
      explore challenges, share practical clinical experiences, and review ethical
      underpinnings surrounding decisions to offer intensive, invasive therapies to
      patients who have a poor prognosis for survival or are likely to be burdened with
      multiple residual comorbidities if survival is achieved. The discussion panel was
      representative of a variety of disciplines including pediatric cardiology,
      cardiac intensive care, nursing, and cardiovascular surgery as well as different
      health-care delivery systems. Key issues discussed included patient's best
      interests, physician obligations, moral distress, and communication in the
      context of decisions about providing therapy for patients with a poor prognosis.

PMID- 29187108
TI  - Right Dominant Atrioventricular Septal Defect: The Road to a Unified Model of
      Echocardiographic Interpretation.

PMID- 29187109
TI  - Modified In Situ Pericardial Rerouting Technique for Scimitar Syndrome Repair.
AB  - Scimitar syndrome repair represents a challenge due to the high incidence of
      postoperative pulmonary venous obstruction associated with classic surgical
      strategies. In situ pericardial rerouting technique has been considered a
      promising alternative approach due to its simplicity and excellent midterm
      results. Access to the left atrium can be difficult in young patients with severe
      dextrocardia and hypoplastic right lung. We describe a modification of the
      original rerouting technique in which the atrial septum is repositioned in order
      to create a wide opening in the lateral aspect of the left atrium and ensure an
      adequate size of the reconstructed pathway.

PMID- 29187110
TI  - Experience with an Acuity Adaptable Care Model for Pediatric Cardiac Surgery.
AB  - BACKGROUND: We describe the implementation of and outcomes associated with an
      acuity adaptable care model for pediatric patients undergoing cardiac surgery.
      METHODS: Consecutive patients undergoing an index cardiac operation between July
      2007 and June 2015 were included. From July 2007 through June 2010, a
      conventional model existed in which patients moved among units and care teams
      based on age, severity of illness, and operative status (conventional group). A
      transitional period existed between July 2010 and June 8, 2012 (transitional
      group). From June 9, 2012, through June 2015, an acuity adaptable model was used
      in which patients remained in the cardiac care unit and received care from the
      same clinical team throughout their hospitalization (acuity adaptable group).
      RESULTS: Included were 2,363 patients: 925 in the conventional group, 520 in the
      transitional group, and 918 in the acuity adaptable group. In relation to the
      conventional group, the adjusted odds of operative mortality in the acuity
      adaptable group was 0.55 (95% confidence interval: 0.26-1.18; P = .12). The
      failure to rescue rate (ie, number of deaths in patients with any complication
      divided by the number of total patients with any complication) decreased
      (conventional group, 8.7%; acuity adaptable group, 4.2%; P = .04). In relation to
      the conventional group, postoperative hospital length of stay tended to be
      shorter in the acuity adaptable group ( P = .07). CONCLUSIONS: The implementation
      of an acuity adaptable care model was feasible in our pediatric cardiac program.
      The favorable associations identified between the new model and outcomes are
      promising but warrant confirmation in a larger, multicenter study.

PMID- 29187111
TI  - Aiming at a Blurry Target: Optimal Therapy for Postoperative JET.

PMID- 29187113
TI  - Immune System in Single Ventricle Patients-A Complex Nexus.

PMID- 29187112
TI  - The Impact of Time to Rate Control of Junctional Ectopic Tachycardia After
      Congenital Heart Surgery.
AB  - BACKGROUND: Junctional ectopic tachycardia (JET) after congenital heart disease
      (CHD) surgery is often self-limiting but is associated with increased risk of
      morbidity and mortality. Contributing factors and impact of time to achieve rate
      control of JET are poorly described. METHODS: From January 2010 to June 2015, a
      retrospective, single-center cohort study was performed of children who developed
      JET after CHD surgery . We classified the cohort into two groups: patients who
      achieved rate control of JET in <=24 hours and in >24 hours. We examined factors
      associated with time to rate control and compared clinical outcomes (mortality,
      duration of mechanical ventilation, length of intensive care unit [ICU], and
      hospital stay) between the two groups. RESULTS: Our cohort included 27 children,
      with a median age of 3 (interquartile range: 0.7-38] months. The most common CHD
      lesions were ventricular septal defect (n = 10, 37%), tetralogy of Fallot (n = 7,
      25.9%), and transposition of the great arteries (n = 4, 14.8%). In all, 15
      (55.6%) and 12 (44.4%) patients achieved rate control of JET in <=24 hours and
      >24 hours, respectively. There was a difference in median mechanical ventilation
      time (97 [21-145) vs 311 [100-676] hours; P = .013) and ICU stay (5.0 [2.0-8.0]
      vs 15.5 [5.5-32.8] days, P = .023) between the patients who achieved faster rate
      control than those who didn't. There was no difference in length of hospital stay
      and mortality between the groups. CONCLUSION: Our study demonstrated that time to
      achieve rate control of JET was associated with increased duration of mechanical
      ventilation and ICU stay.

PMID- 29187114
TI  - Unrepaired Incomplete Pentalogy of Cantrell in a 3-Year-Old Girl.

PMID- 29187116
TI  - Excellence by Design: The Patricia A. Hickey Award for Excellence in
      Cardiovascular Nursing.
AB  - This award reflects the high-impact contributions of pediatric critical care
      nurses that have helped to shape the field. Lessons from an ongoing career in
      nursing leadership are shared by Dr Patricia Hickey. Four themes are highlighted
      which include (1) our role models/mentors, (2) our profession and its impact, (3)
      our teams and environments of excellence, and (4) our bright future. Program and
      practice excellence does not just happen. It requires strategic thinking,
      deliberative processes, risk-taking and guts to create and sustain. A bright
      future is forecasted with stellar contributions of professional nurses and
      interprofessional cardiac critical care teams.

PMID- 29187115
TI  - Tricuspid Valve Repair in Infancy Using Neochordae: Three-Dimensional
      Echocardiographic Imaging.
AB  - Tricuspid regurgitation (TR) in infancy poses a surgical challenge. Both two- and
      three-dimensional echocardiography (3DE) can provide detailed information about
      the mechanism(s) of valve failure and insights into valve adaptation during
      follow-up. We report two patients who underwent tricuspid valve repair using Gore
      Tex neochordae, repairs which were facilitated by and assessed with 3DE. Both
      infants had less than mild residual TR and no valve tethering at hospital
      discharge. Furthermore, follow-up 3DEs have helped to confirm valve competence,
      lack of tethering, and growth of the valve and valve apparatus.

PMID- 29187117
TI  - Practical Considerations in Donation After Circulatory Determination of Death in
      Switzerland.
AB  - Faced with similar issues of organ scarcity to its neighbors, Switzerland has
      developed donation after circulatory determination of death (DCDD) as a way to
      expand the organ pool since 1985. Here, we analyze the history, practical
      considerations, and ethical issues relating to the Swiss donation after
      circulatory death programs. In Switzerland, determination of death for DCDD
      requires a stand-off period of 10 minutes. This time between cardiac arrest and
      the declaration of death is mandated in the guidelines of the Swiss Academy of
      Medical Sciences. As in other DCDD programs, safeguards are put to avoid
      physicians denying lifesaving treatment to savable patients because of being
      influenced by receivers' interest. An additional recommendation could be made:
      Recipients should be transparently informed of the worse graft outcomes with DCDD
      programs and given the possibility to refuse such organs.

PMID- 29187118
TI  - Multifocal human papillomavirus detection in palatine and pharyngeal tonsils.
AB  - BACKGROUND: Multifocal human papillomavirus (HPV) infection into the palatine and
      pharyngeal tonsils, which might be linked to a second primary tumor of HPV
      positive oropharyngeal cancer (OPC), was investigated. PATIENTS AND METHODS: One
      hundred and five patients with various head and neck diseases including 14
      patients with OPC were enrolled in this study. Swabs from the palatine and
      pharyngeal tonsils were collected in each individual, and auto-nested GP5+/GP6+
      PCR for HPV DNA was performed. RESULTS: HPV DNA was detected in the palatine
      tonsil or the pharyngeal tonsil in a small subset of upper respiratory tract
      cancer other than OPC (URTC) and non-cancer diseases. Furthermore, HPV DNA was
      detected in both the palatine and pharyngeal tonsils in the same individual in 2
      of 48 (4%) URTC cases, and 1 of 43 (2%) non-cancer cases. On the other hand, p16
      positive OPC cases demonstrated a higher HPV DNA detection rate (4 of 9, 44.4%)
      compared with other disease groups. CONCLUSION: HPV DNA detection in both the
      palatine and pharyngeal tonsils in the same individual, especially in HPV-OPC,
      suggested the ability of HPV to infect tonsillar tissues of Waldeyer's ring
      multifocally.

PMID- 29187119
TI  - Photocatalytic degradation of diclofenac using TiO2-SnO2 mixed oxide catalysts.
AB  - The complex nature of diclofenac limits its biological degradation, posing a
      serious threat to aquatic organisms. Our present work aims to eliminate
      diclofenac from wastewater through photocatalytic degradation using TiO2-SnO2
      mixed-oxide catalysts under various operating conditions such as catalyst
      loading, initial diclofenac concentration and initial pH. Different molar ratios
      of Ti-Sn (1:1, 5:1, 10:1, 20:1 and 30:1) were prepared by the hydrothermal method
      and were characterized. The results indicated that addition of Sn in small
      quantity enhances the catalytic activity of TiO2. Energy Band gap of the TiO2
      SnO2 catalysts was found to increase with an increase in Tin content. TiO2-SnO2
      catalyst with a molar ratio of 20:1 was found to be the most effective when
      compared to other catalysts. The results suggested that initial drug
      concentration of 20 mg/L, catalyst loading of 0.8 g/L and pH 5 were the optimum
      operating conditions for complete degradation of diclofenac. Also, the TiO2-SnO2
      catalyst was effective in complete mineralization of diclofenac with a maximum
      total organic carbon removal of 90% achieved under ultraviolet irradiation. The
      repeatability and stability results showed that the TiO2-SnO2 catalyst exhibited
      an excellent repeatability and better stability over the repeated reaction
      cycles. The photocatalytic degradation of diclofenac resulted in several
      photoproducts, which were identified through LC-MS.

PMID- 29187120
TI  - Growth and Neurodevelopmental Outcomes of Early, High-Dose Parenteral Amino Acid
      Intake in Very Low Birth Weight Infants: A Randomized Controlled Trial.
AB  - BACKGROUND: Administration of high-dose parenteral amino acids (AAs) to premature
      infants within hours of delivery is currently recommended. This study compared
      the effect of lower and higher AA administration starting close to birth on short
      term growth and neurodevelopmental outcomes at 18-24 months corrected gestational
      age (CGA). METHODS: Infants <1250 g birth weight (n = 168) were randomly assigned
      in a blinded fashion to receive parenteral nutrition providing 1-2 g/kg/d AA and
      advancing daily by 0.5 g/kg/d to a goal of 4 g/kg/d (standard AA) or 3-4 g/kg/d
      and advancing to 4 g/kg/d by day 1. The primary outcome was neurodevelopmental
      outcomes measured by the Bayley Scales of Infant and Toddler Development, Third
      Edition at 18-24 months CGA. Secondary outcomes were growth parameters at 36
      weeks CGA among infants surviving to hospital discharge, serum bicarbonate, serum
      urea nitrogen, creatinine, AA profiles in the first week of life, and incidence
      of major morbidities and mortality. RESULTS: No differences in neurodevelopmental
      outcome were detected between the high and low AA groups. Infants in the high AA
      group had significantly lower mean weight, length, and head circumference
      percentiles than those in the standard AA group at 36 weeks CGA and at hospital
      discharge. These differences did not persist after controlling for birth growth
      parameters, except for head circumference. Infants in the high AA group had
      higher mean serum urea nitrogen than the standard group on each day throughout
      the first week. CONCLUSION: Current recommendations for high-dose AA starting at
      birth are not associated with improved growth or neurodevelopmental outcomes.

PMID- 29187121
TI  - Lipid Injectable Emulsions: Infusion Confusion.
AB  - The commentary addresses discussion regarding the duration of infusion for lipid
      injectable emulsions (ILEs; previously known as intravenous fat emulsion) when
      administered separately from amino acids and dextrose (2:1) admixtures. The
      article by Mundi et al describes the administration time of ILEs administered
      separately as up to 24 hours, while previous American Society for Parenteral and
      Enteral Nutrition documents have outlined the infusion time not to exceed 12
      hours.

PMID- 29187122
TI  - Social determinants of cancer incidence and mortality around the world: an
      ecological study.
AB  - Cancer continues to be a leading cause of mortality and morbidity the world over.
      While the incidence of cancer is projected to increase by 70% over the next two
      decades, some research findings suggest a disproportionate distribution of new
      cancer cases and attendant fatalities across certain regions of the world, with
      poor and lower income countries worse affected at a time when advances in cancer
      research, medical technology, and drug development are giving rise to better
      cancer survival in developed countries. In this study, the role of selected
      social determinants of health in gauging cancer outcomes relative to incidence
      across various countries in different regions of the world was explored. The
      results indicated that the education index, income index, Gini coefficient,
      availability of cancer control policies and programs, as well as health system
      performance have an association with and are good predictors of the mortality to
      incidence ratio (MIR) of lung, breast, cervical, and colorectal cancers. In other
      words, populations with better education, higher incomes and lower inequalities,
      active cancer control policies and programs and high performing health systems
      have better cancer outcomes as reflected in lower MIRs relative to other
      populations.

PMID- 29187123
TI  - A qualitative investigation of the nature of "informal supervision" among
      therapists in training.
AB  - OBJECTIVE: This study investigated how, when, why, and with whom therapists in
      training utilize "informal supervision"-that is, engage individuals who are not
      their formally assigned supervisors in significant conversations about their
      clinical work. METHOD: Participants were 16 doctoral trainees in clinical and
      counseling psychology programs. Semi-structured interviews were conducted and
      analyzed using the Consensual Qualitative Research (CQR) method. RESULTS: Seven
      domains emerged from the analysis, indicating that, in general, participants
      believe that informal and formal supervision offer many of the same benefits,
      including validation, support, and reassurance; freedom and safety to discuss
      doubts, anxieties, strong personal reactions to patients, clinical mistakes and
      challenges; and alternative approaches to clinical interventions. However,
      several differences also emerged between these modes of learning-for example,
      formal supervision is seen as more focused on didactics per se ("what to do"),
      whereas informal supervision is seen as providing more of a "holding
      environment." CONCLUSIONS: Overall, the findings of this study suggest that
      informal supervision is an important and valuable adjunctive practice by which
      clinical trainees augment their professional competencies. Recommendations are
      proposed for clinical practice and training, including the need to further
      specify the ethical boundaries of this unique and essentially unregulated type of
      supervision.

PMID- 29187124
TI  - Factors affecting unsafe behavior in construction projects: development and
      validation of a new questionnaire.
AB  - INTRODUCTION: Occupational safety in general, and construction safety in
      particular, is a complex phenomenon. This study was designed to develop a new
      valid measure to evaluate factors affecting unsafe behavior in the construction
      industry. METHODS: A new questionnaire was generated from qualitative research
      according to the principles of grounded theory. Key measurement properties (face
      validity, content validity, construct validity, reliability and discriminative
      validity) were examined using qualitative and quantitative approaches. The
      receiver operating characteristic curve was used to estimate the discriminating
      power and the optimal cutoff score. RESULTS: Construct validity revealed an
      interpretable 12-factor structure which explained 61.87% of variance. Good
      internal consistency (Cronbach's alpha = 0.94) and stability (intra-class
      correlation coefficient = 0.93) were found for the new instrument. The area under
      the curve, sensitivity and specificity were 0.80, 0.80 and 0.75, respectively.
      The new instrument also discriminated safety performance among the construction
      sites with different workers' accident histories (F = 6.40, p < 0.05).
      CONCLUSION: The new instrument appears to be a valid, reliable and sensitive
      instrument that will contribute to investigating the root causes of workers'
      unsafe behaviors, thus promoting safety performance in the construction industry.

PMID- 29187126
TI  - Simulation-Based Communication Skills Training for Experienced Clinicians to
      Improve Family Conversations About Organ and Tissue Donation.
AB  - INTRODUCTION: The approach, communication skills, and confidence of clinicians
      responsible for raising deceased organ donation may influence families' donation
      decisions. The aim of this study was to increase the preparedness and confidence
      of intensive care clinicians allocated to work in a "designated requester" role.
      DESIGN: We conducted a posttest evaluation of an innovative simulation-based
      training program. Simulation-based training enabled clinicians to rehearse the
      "balanced approach" to family donation conversations (FDCs) in the designated
      requester role. Professional actors played family members in simulated clinical
      settings using authentic scenarios, with video-assisted reflective debriefing.
      Participants completed an evaluation after the workshop. Simple descriptive
      statistical analysis and content analysis were performed. RESULTS: Between
      January 2013 and July 2015, 25 workshops were undertaken with 86 participants; 82
      (95.3%) returned evaluations. Respondents were registered practicing clinicians;
      over half (44/82; 53.7%) were intensivists. Most attended a single workshop.
      Evaluations were overwhelmingly positive with the majority rating workshops as
      outstanding (64/80; 80%). Scenario fidelity, competence of the actors,
      opportunity to practice and receive feedback on performance, and feedback from
      actors, both in and out of character, were particularly valued. Most (76/78;
      97.4%) reported feeling more confident about their designated requester role.
      DISCUSSION: Simulation-based communication training for the designated requester
      role in FDCs increased the knowledge and confidence of clinicians to raise the
      topic of donation.

PMID- 29187125
TI  - Nitro-Oleic Acid (NO2-OA) Release Enhances Regional Angiogenesis in a Rat
      Abdominal Wall Defect Model.
AB  - Ventral hernia is often addressed surgically by the placement of prosthetic
      materials, either synthetic or from allogeneic and xenogeneic biologic sources.
      Despite advances in surgical approaches and device design, a number of
      postsurgical limitations remain, including hernia recurrence, mesh encapsulation,
      and reduced vascularity of the implanted volume. The in situ controlled release
      of angiogenic factors from a scaffold facilitating abdominal wall repair might
      address some of these issues associated with suboptimal tissue reconstruction.
      Furthermore, a biocomposite material that combines the favorable mechanical
      properties achievable with synthetic materials and the bioactivity associated
      with xenogeneic tissue sources would be desirable. In this report, an abdominal
      wall repair scaffold has been designed based on a microfibrous, elastomeric
      poly(ester carbonate)urethane urea matrix integrated with a hydrogel derived from
      decellularized porcine dermis (extracellular matrix [ECM] gel) and poly(lactic-co
      glycolic acid) (PLGA) microspheres loaded with nitro-oleic acid (NO2-OA). NO2-OA
      is an electrophilic fatty acid nitro-alkene derivative that, under hypoxic
      conditions, induces angiogenesis. This scaffold was utilized to repair a rat
      abdominal wall partial thickness defect, hypothesizing that the nitro-fatty acid
      release would facilitate increased angiogenesis at the 8-week endpoint. The
      quantification of neovascularization was conducted by novel methodologies to
      assess vessel morphology and spatial distribution. The repaired abdominal wall
      defects were evaluated by histopathologic methods, including quantification of
      the foreign body response and cellular ingrowth. The results showed that NO2-OA
      release was associated with significantly improved regional angiogenesis. The
      combined biohybrid scaffold and NO2-OA-controlled release strategy also reduced
      scaffold encapsulation, increased wall thickness, and enhanced cellular
      infiltration. More broadly, the three components of the composite scaffold design
      (ECM gel, polymeric fibers, and PLGA microparticles) enable the tuning of
      performance characteristics, including scaffold bioactivity, degradation,
      mechanics, and drug release profile, all decisive factors to better address
      current limitations in abdominal wall repair or other soft tissue augmentation
      procedures.

PMID- 29187127
TI  - The Discussion of Sexual Dysfunction Before and After Kidney Transplantation From
      the Perspective of the Renal Transplant Surgeon.
AB  - INTRODUCTION: Sexual dysfunction (SD) is a common problem in chronic kidney
      disease (CKD) and endures in 50% of patients after kidney transplantation (KTx),
      diminishing patients' expectations of life after KTx. Unfortunately, SD is often
      ignored by renal care providers. Research questions as part of a research project
      among all renal care providers, transplant surgeons' perspectives were obtained
      on sexual health care for KTx recipients, including their opinion on who should
      be accountable for this care. In addition, surgeons' practice and knowledge
      regarding SD were evaluated. DESIGN: A 39-item questionnaire was sent to all
      Dutch surgeons and residents specialized in KTx (n = 47). RESULTS: Response was
      63.8%. None of the respondents discussed SD with their patients, before or after
      surgery. Most important barrier was that surgeons do not feel accountable for it
      (73.9%); 91.7% thought this accountability should lie with the nephrologist.
      Another barrier was insufficient knowledge (39.1%). In 75% of the respondents,
      (almost) no knowledge regarding SD was present and 87.5% noticed education on SD
      was insufficient during residence training. DISCUSSION: Dutch renal transplant
      surgeons rarely discuss SD with their patients with CKD, as they do not feel
      accountable for it; this accountability was appointed to the nephrologist.
      Knowledge and education regarding SD were found insufficient in enabling surgeons
      and for some it reflects in barriers toward discussing SD. Results emphasize that
      accountability for providing sexual health care to patients with CKD should lie
      elsewhere; however, surgeons could briefly provide information on sexual health
      after KTx, so unfulfilled expectations may be prevented.

PMID- 29187128
TI  - Radiotherapy in Patients With De Novo Cancer After Transplantation.
AB  - For frequently seen noncomplex cancer presentation, it is important to use rapid,
      effective, and inexpensive radiotherapy methods. However, for the complex cancer,
      these sophisticated radiotherapy techniques can decrease morbidity and mortality
      in our transplant patients and should be considered.

PMID- 29187129
TI  - The Importance of Self-Plagiarism in Publication.

PMID- 29187130
TI  - Associations Between Medication Nonadherence and Perceived Stress Among Kidney
      Transplant Recipients.

PMID- 29187132
TI  - Lymphatic Leak After Intestinal Transplantation: Aspects of the Donor Technique.
AB  - The rich component of lymphatics makes the intestine prone to leaks of lymph
      after transplantation secondary to their transection during procurement. We
      describe our technique for isolation and ligation of the small lymphatics at the
      root of the mesentery during the procurement of the small intestine and report
      our experience with the management of lymphatic leaks posttransplant.

PMID- 29187131
TI  - Haptoglobin 2-2 Genotype, Patient, and Graft Survival in Renal Transplant
      Recipients.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death in renal
      transplant recipients. An association between haptoglobin genotype 2-2 and
      cardiovascular disease has been found in patients with diabetes mellitus and
      liver transplant recipients. To date, the role of haptoglobin genotype after
      renal transplantation has not been studied. METHODS: In this single-center
      retrospective cohort study of 1975 adult Norwegian transplant recipients, who
      underwent transplantation between 1999 and 2011, we estimated the risk of all
      cause and cardiovascular mortality and overall and death-censored graft loss for
      patients with haptoglobin genotype 2-2 compared to genotype 2-1 or 1-1, after
      adjustment for confounders and competing risks. RESULTS: We found no associations
      between haptoglobin genotype 2-2 and cardiovascular mortality (subdistributional
      hazard ratio 1.08, 95% confidence interval 0.78-1.49; P = .63). We also failed to
      detect any association between haptoglobin 2-2 genotype and all-cause mortality,
      overall graft loss, and death-censored graft loss. Similar results were found in
      the subpopulation of transplant recipients with diabetes. CONCLUSION: In this
      large cohort of kidney transplant recipients, we could not demonstrate any
      association between haptoglobin 2-2 genotype and patient or graft survival after
      renal transplantation.

PMID- 29187133
TI  - Peer Leaders Increase Organ Donor Designation Among Members of Historically
      African American Fraternities and Sororities.
AB  - INTRODUCTION: Health education programs can positively impact organ donor
      designation among African Americans, a disproportionately represented group on
      the transplant waiting list. Alumni chapters of historically African American
      sororities and fraternities are a novel setting for organ donation education and
      research. RESEARCH QUESTIONS: This study tested the effectiveness of a lay health
      advisor model to increase donor designation registrations on the Michigan Organ
      Donor Registry among members of Midwest alumni chapters. The secondary outcome
      was change in attitudes toward donation assessed by pre-post questionnaire.
      DESIGN: Sorority/fraternity members were trained to deliver educational
      presentations during a 12-month period. Follow-up messaging consisted of tailored
      newsletters and e-mails. A cluster randomized design was utilized with 25
      chapters (16 sororities and 9 fraternities) assigned to intervention (organ
      donation) or comparison (chronic disease). RESULTS: Odds of signing up for the
      donor registry were 1.45 times higher for the intervention group than the
      comparison group. Among those identified as nondonors at baseline, the odds of
      signing up were 1.58 times higher for intervention than comparison. DISCUSSION:
      Using lay health advisors in African American sororities and fraternities can
      increase enrollment in a donor registry. Alumni chapters offer a unique and
      viable setting for organ donation education and research; relationship building
      with chapter officials is key to success.

PMID- 29187134
TI  - Correlation Between Renal Cortical Stiffness and Histological Determinants by
      Point Shear-Wave Elastography in Patients With Kidney Transplantation.
AB  - INTRODUCTION: Renal allograft biopsy is the gold standard for the detection of
      histological lesions of chronic allograft dysfunction. The identification of a
      noninvasive routine test would be desirable. Elastosonography is used to assess
      tissue stiffness according to viscosity, and no data are available on the use of
      point quantification shear-wave elastography (ElastPQ) for the evaluation of
      renal chronic lesions. RESEARCH QUESTION: To evaluate the feasibility of ElastPQ
      to assess cortical allograft stiffness and to determine the correlation of
      clinical, biological, and pathological factors with the diagnostic accuracy of
      kidney stiffness values in patients with histological lesions. DESIGN: Forty-two
      patients underwent kidney transplant biopsy and 10 valid measurements of ElastPQ,
      blindly performed by 2 operators. The interobserver reproducibility was assessed
      according to intraclass correlation coefficient. The ElastPQ measurements and the
      clinical data were compared using the Spearman correlation analysis. RESULTS:
      97.6% reliable measurements were obtained using ElastPQ, with an excellent
      interobserver agreement. The kidney stiffness was significantly higher in the
      patients with a time since transplantation >12 months and was correlated with
      chronic lesions (interstitial fibrosis, tubular atrophy transplant
      glomerulopathy, and mesangial matrix), with the interstitial fibrosis/tubular
      atrophy, score and with the sum of the scores of the chronic lesions. Mesangial
      matrix increase is the only independent determinant of kidney stiffness.
      DISCUSSION: ElastPQ is a noninvasive, reproducible, and sensitive diagnostic tool
      able to detect moderate/severe chronic lesions. Its routine use during follow-up
      can identify patients eligible for biopsy, which remains the gold standard exam
      for detecting chronic allograft dysfunction.

PMID- 29187135
TI  - A Clustered Randomized Trial of an Educational Intervention During Transplant
      Evaluation to Increase Knowledge of Living Donor Kidney Transplant.
AB  - INTRODUCTION: Maximizing education about living donor kidney transplant (LDKT)
      during the in-person evaluation at the transplant center may increase the numbers
      of kidney patients pursuing LDKT. Research Questions and Design: To test the
      effectiveness of a 1-time LDKT educational intervention, we performed a cluster
      randomized trial among 499 patients who presented for evaluation of kidney
      transplant. We compared usual care education (n = 250) versus intensive LDKT
      education (n = 249), which was implemented only on the evaluation day and
      consisted of viewing a 25-minute video of information and stories about LDKT and
      discussion of LDKT possibilities with an educator. Our primary outcome was
      knowledge of LDKT, 1 week after the transplant evaluation. RESULTS: One week
      after evaluation, patients who received intensive education had higher knowledge
      than patients who received usual care (12.7 vs. 11.7; P = .0008), but there were
      no differences in postevaluation readiness for LDKT. Among patients who had not
      previously identified a potential living donor, receiving intensive education was
      associated with increased willingness to take steps toward LDKT. DISCUSSION: In
      conclusion, expansion of LDKT education within the evaluation day may be helpful,
      but interventions that are implemented at multiple times and for greater duration
      may be necessary to ensure larger and long-term behavioral changes in pursuit of
      LDKT.

PMID- 29187136
TI  - Results of a Patient Survey for Assessment Services in Renal Transplant Patients
      With a History of Cancer.
AB  - Patients with cancer who require a kidney transplant often face a prolonged time
      on the waiting list to ensure a sufficient relapse-free time. Patients and
      relatives were invited to the patient assessment service where they get an
      individualized risk assessment and a recommendation for transplantation and
      waiting period directly from an expert panel. We investigated in 31 patients who
      filled out questionnaires concerning depression, anxiety, distress, and quality
      of life and were interviewed for their satisfaction, experiences, and
      circumstances of the counseling. In 12 (39%) of the 31 patients, a recommendation
      for transplantation could be made, although the regular waiting period was not
      yet achieved. The assessment service was received as very good or good by 22
      (79%) of 28 patients. We found no relevant differences in patients with regular
      and shortened waiting time. An interdisciplinary assessment service is a valuable
      instrument to help with a decision-making between 2 life-threatening conditions.

PMID- 29187137
TI  - Evaluation of Filgrastim Therapy in Kidney Transplant Recipients.
AB  - CONTEXT: Neutropenia is associated with a high risk of serious infections in
      kidney transplant recipients. There are no sufficient studies of using
      granulocyte colony-stimulating factors, such as filgrastim, in renal transplant
      recipients to establish a clear, specified role of this off-label indication.
      Using filgrastim in these patients may increase the risk of rejection by
      overstimulating the immune system. OBJECTIVE: To evaluate the use of filgrastim
      in adult kidney transplant recipients presenting with neutropenia. PATIENTS AND
      DESIGN: Data were obtained from a medication utilization report of filgrastim in
      kidney transplant recipients at our center from September 2012 to August 2015.
      Main Outcome Measure(s) and Results: There were 28 cases of neutropenia that were
      treated with a range of 1 to 5 doses of filgrastim 300 or 480 MUg, with a mean of
      1.79 doses. The mean total dose of filgrastim administered per episode of
      neutropenia was 632 MUg (8.6 MUg/kg). Overall, 87.5% of the cases achieved a
      white blood cell count of at least 3 * 109 cells/L within 7 days of hospital
      discharge. There were no cases of infection or acute rejection following
      treatment. CONCLUSIONS: The use of filgrastim in kidney transplant recipients
      demonstrated success in reversing neutropenia. Short courses of therapy were
      required with minimal adverse events. Patients who required readmission were
      successfully re-treated. Additional studies are required to determine the most
      effective dose and duration of treatment.

PMID- 29187138
TI  - Up to a Third of Renal Transplant Recipients Have Deficiencies in Cognitive
      Functioning.
AB  - INTRODUCTION: Kidney transplantation is beneficial in improving cognitive
      abilities in patients with chronic kidney disease; however, there is still
      uncertainty concerning which cognitive domains benefit and to what extent. AIM:
      In the present study, cognitive functioning of renal transplant recipients was
      compared to normative data. Sociodemographic and clinical parameters that were
      associated with low cognitive performance were identified. DESIGN: A total of 109
      renal transplant recipients (63% men) participated in the study, with a mean age
      of 51.8 (standard deviation [SD] = 14.2) years. The cognitive test battery
      consisted of measurements assessing memory, attention, executive function,
      reproductive, and deductive ability. RESULTS: In all tests, participants showed
      mean scores ranging within 1 SD of the population means. However, except for
      tests measuring memory, the percentage of participants scoring more than 1 SD
      below normed means was higher than expected in a normal distribution of
      performance. In certain tests, up to a third of the participants scored below
      average. Participants with continuous low performance (11%) showed higher age,
      poorer education, a longer time since transplantation, higher serum levels of
      urea and creatinine, and were more likely to have a deceased donor allograft.
      DISCUSSION: Altough cognitive performance in renal transplant recipients matches
      normative data and confirms former findings, the amount of patients scoring more
      than 1 SD below average suggests that there are a considerable number of patients
      whose cognitive performance in certain domains lies below those of the general
      population. The identified sociodemographic and biochemical factors might be
      helpful to identify renal transplant recipients at risk.

PMID- 29187139
TI  - PON-SC - program for identifying steric clashes caused by amino acid
      substitutions.
AB  - BACKGROUND: Amino acid substitutions due to DNA nucleotide replacements are
      frequently disease-causing because of affecting functionally important sites. If
      the substituting amino acid does not fit into the protein, it causes structural
      alterations that are often harmful. Clashes of amino acids cause local or global
      structural changes. Testing structural compatibility of variations has been
      difficult due to the lack of a dedicated method that could handle vast amounts of
      variation data produced by next generation sequencing technologies. RESULTS: We
      developed a method, PON-SC, for detecting protein structural clashes due to amino
      acid substitutions. The method utilizes side chain rotamer library and tests
      whether any of the common rotamers can be fitted into the protein structure. The
      tool was tested both with variants that cause and do not cause clashes and found
      to have accuracy of 0.71 over five test datasets. CONCLUSIONS: We developed a
      fast method for residue side chain clash detection. The method provides in
      addition to the prediction also visualization of the variant in three dimensional
      structure.

PMID- 29187140
TI  - Somatic embryogenesis from seeds in a broad range of Vitis vinifera L. varieties:
      rescue of true-to-type virus-free plants.
AB  - BACKGROUND: Somatic embryogenesis is the preferred method for cell to plant
      regeneration in Vitis vinifera L. However, low frequencies of plant embryo
      conversion are commonly found. In a previous work we obtained from cut-seeds of a
      grapevine infected with the Grapevine leafroll associated viruses 1 and 3 (GLRaV
      1 and GLRaV-3), high rates of direct regeneration, embryo plant conversion and
      sanitation. The aim of this study is to evaluate the usefulness of this procedure
      for regeneration of other grapevine varieties which include some infected with
      one to three common grapevine viruses (GLRaV-3, Grapevine fanleaf virus (GFLV)
      and Grapevine fleck virus (GFkV)). As grapevine is highly heterozygous, it was
      necessary to select from among the virus-free plants those that regenerated from
      mother tissues around the embryo, (true-to-type). RESULTS: Somatic embryogenesis
      and plant regeneration were achieved in a first experiment, using cut-seeds from
      the 14 grapevine varieties Airen, Cabernet Franc, Cabernet Sauvignon, Mencia,
      Merlot, Monastrell, Petit Verdot, Pinot Blanc (infected by GFLV and GFkV), Pinot
      Gris, Pinot Meunier, Pinot Noir, Syrah, Tempranillo (infected by GFLV), and
      Verdil. All regenerated plants were confirmed to be free of GFkV whereas at least
      68% sanitation was obtained for GFLV. The SSR profiles of the virus-free plants
      showed, in both varieties, around 10% regeneration from mother tissue (the same
      genetic make-up as the mother plant). In a second experiment, this procedure was
      used to sanitize the varieties Cabernet Franc, Godello, Merlot and Valenci Blanc
      infected by GLRaV-3, GFkV and/or GFLV. CONCLUSIONS: Cut-seeds can be used as
      explants for embryogenesis induction and plant conversion in a broad range of
      grapevine varieties. The high regeneration rates obtained with this procedure
      facilitate the posterior selection of true-to-type virus-free plants. A
      sanitation rate of 100% was obtained for GFkV as this virus is not seed
      transmitted. However, the presence of GLRaV-3 and GFLV in some of the regenerated
      plants showed that both viruses are seed-transmitted. The regeneration of true-to
      type virus-free plants from all infected varieties indicates that this
      methodology may represent an alternative procedure for virus cleaning in
      grapevine.

PMID- 29187141
TI  - Experiences and needs of carers of Aboriginal children with a disability: a
      qualitative study.
AB  - BACKGROUND: Australian parents/carers of a person with a disability experience
      higher rates of depression, more financial stress, and are twice as likely to be
      in poor physical health than the general population. Aboriginal and Torres Strait
      Islander peoples experience worse health, social and economic outcomes than other
      Australians, and those with a disability face 'double disadvantage'. This study
      aimed to better understand the experiences and needs of parents/carers/families
      of Aboriginal children with a disability. METHODS: Semi-structured in-depth
      interviews were conducted with parents or primary carers of Aboriginal children
      aged zero-eight with disability. Interviews were analysed using thematic
      analysis. RESULTS: Nineteen women (sixteen mothers and three grandmothers) were
      interviewed. More than half were lone carers (without a partner or spouse).
      Participants described their experiences, including challenges and facilitators,
      to providing and accessing care, impacts on their health and wellbeing, and
      associated economic and non-economic costs of caregiving. Financial strain and
      social isolation was particularly prominent for lone carers. CONCLUSIONS:
      Tailoring services to the needs of carers of Aboriginal children with a
      disability means supporting kinship caregiving, facilitating engagement with
      other Aboriginal families, and streamlining services and systems to mitigate
      costs. The experiences described by our participants depict an intersection of
      race, socio-economic status, gender, disability, and caregiving. Services and
      funding initiatives should incorporate such intersecting determinants in planning
      and delivery of holistic care.

PMID- 29187142
TI  - Gut microbiota-mediated generation of saturated fatty acids elicits inflammation
      in the liver in murine high-fat diet-induced steatohepatitis.
AB  - BACKGROUND: The gut microbiota plays crucial roles in the development of non
      alcoholic steatohepatitis (NASH). However, the precise mechanisms by which
      alterations of the gut microbiota and its metabolism contributing to the
      pathogenesis of NASH are not yet fully elucidated. METHODS: Mice were fed with a
      recently reported new class of high-fat diet (HFD), steatohepatitis-inducing HFD
      (STHD)-01 for 9 weeks. The composition of the gut microbiota was analyzed by T
      RFLP. Luminal metabolome was analyzed using capillary electrophoresis and liquid
      chromatography time-of-flight mass spectrometry (CE- and LC-TOFMS). RESULTS: Mice
      fed the STHD-01 developed NASH-like pathology within a short period. Treatment
      with antibiotics prevented the development of NASH by STHD-01. The composition of
      the gut microbiota and its metabolic activities were markedly perturbed in the
      STHD-01-fed mice, and antibiotic administration normalized these changes. We
      identified that long-chain saturated fatty acid and n-6 fatty acid metabolic
      pathways were significantly altered by STHD-01. Of note, the changes in gut
      lipidome caused by STHD-01 were mediated by gut microbiota, as the depletion of
      the gut microbiota could reverse the perturbation of these metabolic pathways. A
      saturated long-chain fatty acid, palmitic acid, which accumulated in the STHD-01
      group, activated liver macrophages and promoted TNF-alpha expression.
      CONCLUSIONS: Lipid metabolism by the gut microbiota, particularly the saturation
      of fatty acids, affects fat accumulation in the liver and subsequent liver
      inflammation in NASH.

PMID- 29187143
TI  - DMRfinder: efficiently identifying differentially methylated regions from MethylC
      seq data.
AB  - BACKGROUND: DNA methylation is an epigenetic modification that is studied at a
      single-base resolution with bisulfite treatment followed by high-throughput
      sequencing. After alignment of the sequence reads to a reference genome,
      methylation counts are analyzed to determine genomic regions that are
      differentially methylated between two or more biological conditions. Even though
      a variety of software packages is available for different aspects of the
      bioinformatics analysis, they often produce results that are biased or require
      excessive computational requirements. RESULTS: DMRfinder is a novel computational
      pipeline that identifies differentially methylated regions efficiently. Following
      alignment, DMRfinder extracts methylation counts and performs a modified single
      linkage clustering of methylation sites into genomic regions. It then compares
      methylation levels using beta-binomial hierarchical modeling and Wald tests.
      Among its innovative attributes are the analyses of novel methylation sites and
      methylation linkage, as well as the simultaneous statistical analysis of multiple
      sample groups. To demonstrate its efficiency, DMRfinder is benchmarked against
      other computational approaches using a large published dataset. Contrasting two
      replicates of the same sample yielded minimal genomic regions with DMRfinder,
      whereas two alternative software packages reported a substantial number of false
      positives. Further analyses of biological samples revealed fundamental
      differences between DMRfinder and another software package, despite the fact that
      they utilize the same underlying statistical basis. For each step, DMRfinder
      completed the analysis in a fraction of the time required by other software.
      CONCLUSIONS: Among the computational approaches for identifying differentially
      methylated regions from high-throughput bisulfite sequencing datasets, DMRfinder
      is the first that integrates all the post-alignment steps in a single package.
      Compared to other software, DMRfinder is extremely efficient and unbiased in this
      process. DMRfinder is free and open-source software, available on GitHub (
      github.com/jsh58/DMRfinder ); it is written in Python and R, and is supported on
      Linux.

PMID- 29187144
TI  - Non-alcoholic fatty liver disease and its associations among adolescents in an
      urban, Sri Lankan community.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common problem across
      the world. We aimed to determine the prevalence of NAFLD and its associations in
      Sri Lankan adolescents living in an urban Sri Lankan community. METHOD: The study
      population consisted of the birth cohort of the year 2000, residing in the Ragama
      Medical Officer of Health area. Socio-demographic and anthropometric data
      [anthropometric measurements, blood pressure and total body fat distribution] of
      these adolescents were collected by trained data collectors. Fasting blood sugar,
      serum insulin, fasting serum lipids and serum alanine aminotransferase (ALT)
      levels were measured and an abdominal ultrasound was performed. NAFLD was
      diagnosed on established ultrasound criteria for fatty liver and absent alcohol
      consumption. RESULTS: The study sample consisted of 499 adolescents [263 (51.8%)
      girls]. Forty two (8.4%) had NAFLD. NAFLD was significantly associated with being
      breast fed for less than 4 months (33.3% vs. 17.1 in controls, p = 0.02), higher
      waist circumference (prevalence risk ratio 83.3/20.3, 4.1, p < 0.0001), higher
      body mass index (prevalence risk ratio 40.5/4.8, 8.4, p < 0/0001),higher HOMA-IR
      (3.7 vs. 1.9, p < 0.0001) and high triglycerides (prevalence risk ratio 14.3/5.8,
      2.5, p = 0.033). Adolescents with NAFLD also had a higher amount of total body
      fat (p < 0.001) and subcutaneous fat (p < 0.001) than those without NAFLD. The
      number of children with metabolic derangements was higher among adolescents with
      NAFLD than those without (85.8 vs 26.3 in controls, p < 0.0001), but a family
      history of hypertension, diabetes, myocardial infarction or dyslipidaemia were
      not. CONCLUSION: Prevalence of NAFLD was high in Sri Lankan adolescents, and was
      associated with metabolic derangements, especially obesity, insulin resistance
      and early cessation of breast feeding.

PMID- 29187145
TI  - 'Sussing that doctor out.' Experiences and perspectives of people affected by
      hepatitis C regarding engagement with private general practitioners in South
      Australia: a qualitative study.
AB  - BACKGROUND: Australians with chronic hepatitis C (HCV) can access affordable
      Direct Acting Antiviral (DAA) treatments with high cure rates (>90%), via General
      Practitioners (GPs). Benefits from this treatment will be maximised if people
      with HCV readily disclose and engage with private GPs regarding HCV-related
      issues. Investigating the perceptions and experiences of people affected by HCV
      with GPs can allow for this pathway to care for HCV to be improved. METHODS: In
      2013-2014, 22 purposively sampled participants from South Australia (SA) were
      interviewed. They a) had contracted or were at risk of hepatitis C (n = 10), b)
      were key workers who had clients affected by HCV (n = 6), and c) met both a) and
      b) criteria (n = 6). The semi-structured interviews were recorded, transcribed
      and thematically analysed. RESULTS: People affected by HCV viewed GPs as a source
      of general healthcare but, due to negative experiences and perceptions, many
      developed a strategy of "sussing" out doctors before engaging with and disclosing
      to a GP regarding HCV-related issues. Participants were doubtful about the
      benefits of engagement and disclosure, and did not assume that they would be
      provided best-practice care in a non-discriminatory, non-judgemental way. They
      perceived risks to confidentiality and risks of changes to the care they received
      from GPs upon disclosure. CONCLUSION: GPs may need to act in ways that counteract
      the perceived risks and persuade people affected by HCV of the benefits of
      seeking HCV-related care.

PMID- 29187146
TI  - Determination of antimicrobial susceptibility patterns in Staphylococcus aureus
      strains recovered from patients at two main health facilities in Kabul,
      Afghanistan.
AB  - BACKGROUND: Staphylococcus aureus (S. aureus) is a major pathogen implicated in
      skin and soft tissue infections, abscess in deep organs, toxin mediated diseases,
      respiratory tract infections, urinary tract infections, post-surgical wound
      infections, meningitis and many other diseases. Irresponsible and over use of
      antibiotics has led to an increased presence of multidrug resistant organisms and
      especially methicillin resistant Staphylococcus aureus (MRSA) as a major public
      health concern in Afghanistan. As a result, there are many infections with many
      of them undiagnosed or improperly diagnosed. We aimed to establish a baseline of
      knowledge regarding the prevalence of MRSA in Kabul, Afghanistan, as well as S.
      aureus antimicrobial susceptibility to current available antimicrobials, while
      also determining those most effective to treat S. aureus infections. METHODS:
      Samples were collected from patients at two main Health facilities in Kabul
      between September 2016 and February 2017. Antibiotic susceptibility profiles were
      determined by the disc diffusion method and studied using standard CLSI
      protocols. RESULTS: Out of 105 strains of S. aureus isolated from pus, urine,
      tracheal secretions, and blood, almost half (46; 43.8%) were methicillin
      sensitive Staphylococcus aureus (MSSA) while 59 (56.2%) were Methicillin
      resistant Staphylococcus aureus (MRSA). All strains were susceptible to
      vancomycin. In total, 100 (95.2%) strains were susceptible to rifampicin, 96
      (91.4%) susceptible to clindamycin, 94 (89.5%) susceptible to imipenem, 83
      (79.0%) susceptible to gentamicin, 81(77.1%) susceptible to doxycycline, 77
      (77.1%) susceptible to amoxicillin + clavulanic acid, 78 (74.3%) susceptible to
      cefazolin, 71 (67.6%) susceptible to tobramycin, 68 (64.8%) susceptible to
      chloramphenicol, 60 (57.1%) were susceptible to trimethoprim-sulfamethoxazole, 47
      (44.8%) susceptible to ciprofloxacin, 38 (36.2%) susceptible to azithromycin and
      erythromycin, 37 (35.2%) susceptible to ceftriaxone and 11 (10.5%) were
      susceptible to cefixim. Almost all (104; 99.05%) were resistant to penicillin G
      and only 1 (0.95%) was intermediate to penicillin G. Interestingly, 74.6% of MRSA
      strains were azithromycin resistant with 8.5% of them clindamycin resistant.
      Ninety-six (91.4%) of the isolates were multi-drug resistant. CONCLUSIONS: There
      was a high rate of Methicillin resistance (56.2%) among S. aureus strains in the
      samples collected and most (91.4%) were multidrug resistant. The most effective
      antibiotics to treat Staph infections were vancomycin, rifampicin, imipenem,
      clindamycin, amoxicillin-clavulanic acid, cefazolin, gentamicin and doxycycline.
      The least effective were azithromycin, ceftriaxone, cefixim and penicillin. We
      recommend that, where possible, in every case of S. aureus infection in Kabul,
      Afghanistan, Antibiotic susceptibility testing (AST) should be performed and
      responsible use of antibiotics should be considered.

PMID- 29187147
TI  - Genome-wide analysis of miRNAs in Carya cathayensis.
AB  - BACKGROUND: MicroRNA (miRNA) plays an important role in plant development
      regulation. Hickory is an economically important plant in which the amount of
      flowering determines its production. RESULTS: Here, 51 conserved miRNAs, which
      belong to 16 families and 195 novel miRNAs were identified in hickory genome. For
      each conserved miRNA family, we used sequences from hickory and other plants to
      construct a phylogenetic tree, which shows that each family has members in
      hickory. Some of the conserved miRNA families (i.e., miR167 and miR397) have more
      members in hickory than in other plants because of gene expansion. MiR166
      exhibited tandem duplication with three copies being observed. Many members of
      these conserved miRNA families were detected in hickory flowers, and the
      expression patterns of target genes were opposite to those of the related miRNAs,
      indicating that miRNAs may have important functions in floral regulation of
      hickory. CONCLUSIONS: Taken together, a comprehensive analysis was conducted to
      identify miRNAs produced in hickory flower organs, demonstrating functional
      conservation and diversity of miRNA families among hickory, Arabidopsis, grape,
      and poplar.

PMID- 29187149
TI  - DBNorm: normalizing high-density oligonucleotide microarray data based on
      distributions.
AB  - BACKGROUND: Data from patients with rare diseases is often produced using
      different platforms and probe sets because patients are widely distributed in
      space and time. Aggregating such data requires a method of normalization that
      makes patient records comparable. RESULTS: This paper proposed DBNorm,
      implemented as an R package, is an algorithm that normalizes arbitrarily
      distributed data to a common, comparable form. Specifically, DBNorm merges data
      distributions by fitting functions to each of them, and using the probability of
      each element drawn from the fitted distribution to merge it into a global
      distribution. DBNorm contains state-of-the-art fitting functions including
      Polynomial, Fourier and Gaussian distributions, and also allows users to define
      their own fitting functions if required. CONCLUSIONS: The performance of DBNorm
      is compared with z-score, average difference, quantile normalization and ComBat
      on a set of datasets, including several that are publically available. The
      performance of these normalization methods are compared using statistics,
      visualization, and classification when class labels are known based on a number
      of self-generated and public microarray datasets. The experimental results show
      that DBNorm achieves better normalization results than conventional methods.
      Finally, the approach has the potential to be applicable outside bioinformatics
      analysis.

PMID- 29187148
TI  - The development of the DISCO-RC for measuring children's discomfort during
      research procedures.
AB  - BACKGROUND: There is a need for data on children's self-reported discomfort in
      clinical research, helping ethics committees to make their evaluation of
      discomfort described in study protocols evidence-based. Since there is no
      appropriate instrument to measure children's discomfort during medical research
      procedures, we aimed to develop a generic, short and child-friendly instrument:
      the DISCO-RC questionnaire (DISCOmfort in Research with Children). METHODS: This
      article describes the six steps of the development of the DISCO-RC. First, we
      updated a literature search on children's self-reported discomfort in clinical
      research to get insight in what words are used to measure discomfort (step 1).
      Subsequently, we interviewed 46 children (6-18 years) participating in research
      to get insight into important forms of discomfort for children (step 2), and
      asked them about their preferred response option for measuring discomfort (step
      3). Next, we consulted nine paediatric research professionals from various
      backgrounds for input on the content and feasibility of the DISCO-RC (step 4).
      Based on the previous steps, we developed a draft version of the DISCO-RC, which
      we discussed with the professionals. The DISCO-RC was then pretested in 25
      children to ensure face-validity from the child's perspective and feasibility
      (step 5). Finally, validity, reliability and internal consistency were tested
      (step 6). RESULTS: The search-update revealed several words used for measuring
      discomfort in research (e.g. 'worries', 'unpleasantness'). The interviews gave
      insight into important forms of discomfort for children in research (e.g. 'pain',
      'boredom'). Children preferred a 5-point Likert scale as response option for the
      DISCO-RC. The experts recommended a short, digital instrument involving different
      forms of discomfort, and measuring discomfort of individual research procedures.
      Pretesting of the DISCO-RC resulted in a few layout changes, and feedback from
      the children confirmed the feasibility of the DISCO-RC. Convergent validity and
      test-retest reliability were acceptable. Internal consistency based on item-rest
      correlations and Cronbach's alpha were low, as expected. CONCLUSIONS: The DISCO
      RC is a generic, practical and psychometrically sound instrument for measuring
      children's discomfort during research procedures. It contributes to make the
      evaluation of discomfort in paediatric research evidence-based. Therefore, we
      recommend including the DISCO-RC as standard component of paediatric research
      studies.

PMID- 29187150
TI  - Identification of pathogens for differential diagnosis of fever with jaundice in
      the Central African Republic: a retrospective assessment, 2008-2010.
AB  - BACKGROUND: Febrile jaundice results clinically in generalized yellow coloration
      of the teguments and mucous membranes due to excess plasma bilirubin, accompanied
      by fever. Two types are found: conjugated and unconjugated bilirubin jaundice.
      Jaundice is a sign in several diseases due to viruses (viral hepatitis and
      arbovirus), parasites (malaria) and bacteria (leptospirosis). In the Central
      African Republic (CAR), only yellow fever is included on the list of diseases for
      surveillance. The aim of this study was to identify the other pathogens that can
      cause febrile jaundice, for better management of patients. METHODS: Between 2008
      and 2010, 198 sera negative for yellow fever IgM were randomly selected from 2177
      samples collected during yellow fever surveillance. Laboratory analyses targeted
      four groups of pathogens: hepatitis B, C, delta and E viruses; dengue,
      chikungunya, Zika, Crimean-Congo haemorrhagic fever, West Nile and Rift Valley
      arboviruses; malaria parasites; and bacteria (leptospirosis). RESULTS: Overall,
      30.9% sera were positive for hepatitis B, 20.2% for hepatitis E, 12.3% for
      hepatitis C and 8.2% for malaria. The majority of positive sera (40.4%) were from
      people aged 16-30 years. Co-infection with at least two of these pathogens was
      also found. CONCLUSION: These findings suggest that a systematic investigation
      should be undertaken of infectious agents that cause febrile jaundice in the CAR.

PMID- 29187151
TI  - Pediatric premedication: a double-blind randomized trial of dexmedetomidine or
      ketamine alone versus a combination of dexmedetomidine and ketamine.
AB  - BACKGROUND: Preoperative anxiety is common in pediatric patients. When
      dexmedetomidine is used alone for sedation as premedication, children tend to
      awaken when separated from their parents, and body movements occur during
      invasive procedures. We tested the hypothesis that the combination of
      dexmedetomidine and ketamine may be a useful premedication to alleviate
      preoperative anxiety and improve cooperation during intravenous cannulation in
      pediatric patients, while producing minimal adverse events. METHODS: A total of
      135 children, aged 2-5 years and American Society of Anesthesiologists status I
      II, scheduled for eye surgery were randomly allocated to receive intranasal
      dexmedetomidine 2.5 MUg/kg (group D), oral ketamine 3 mg/kg and intranasal
      dexmedetomidine 2 MUg/kg (group DK), or oral ketamine 6 mg/kg (group K) 30 min
      before surgery. Sedation state was evaluated every 10 min after premedication and
      emotional state was assessed during separation from their parents and peripheral
      intravenous cannulation. Adverse events were recorded for 24 h postoperatively.
      The primary endpoint was the rate of successful intravenous cannulation. RESULTS:
      The rate of successful venous cannulation was 47% with dexmedetomidine alone, 68%
      with ketamine alone, and 80% with combined premedication (P = 0.006). The rate of
      satisfactory separation from parents was not different among groups. The
      incidence of adverse events was higher in group K compared with the other two
      groups (postoperative vomiting, P = 0.0041; respiratory-related complications
      during the perioperative period, P = 0.0032; and postoperative
      psychological/psychiatric adverse events, P = 0.0152). CONCLUSION: The
      combination of intranasal dexmedetomidine 2 MUg/kg and oral ketamine 3 mg/kg
      produces satisfactory separation from parents and more successful venous
      cannulation, allowing children to smoothly accept induction of general
      anesthesia. TRIAL REGISTRATION: Chinese Clinical Trial Register (Unique
      identifier: ChiCTR-TRC-14004475 , Date of registration: 2 April 2014).

PMID- 29187152
TI  - A proximity-based graph clustering method for the identification and application
      of transcription factor clusters.
AB  - BACKGROUND: Transcription factors (TFs) form a complex regulatory network within
      the cell that is crucial to cell functioning and human health. While methods to
      establish where a TF binds to DNA are well established, these methods provide no
      information describing how TFs interact with one another when they do bind. TFs
      tend to bind the genome in clusters, and current methods to identify these
      clusters are either limited in scope, unable to detect relationships beyond motif
      similarity, or not applied to TF-TF interactions. METHODS: Here, we present a
      proximity-based graph clustering approach to identify TF clusters using either
      ChIP-seq or motif search data. We use TF co-occurrence to construct a filtered,
      normalized adjacency matrix and use the Markov Clustering Algorithm to partition
      the graph while maintaining TF-cluster and cluster-cluster interactions. We then
      apply our graph structure beyond clustering, using it to increase the accuracy of
      motif-based TFBS searching for an example TF. RESULTS: We show that our method
      produces small, manageable clusters that encapsulate many known, experimentally
      validated transcription factor interactions and that our method is capable of
      capturing interactions that motif similarity methods might miss. Our graph
      structure is able to significantly increase the accuracy of motif TFBS searching,
      demonstrating that the TF-TF connections within the graph correlate with
      biological TF-TF interactions. CONCLUSION: The interactions identified by our
      method correspond to biological reality and allow for fast exploration of TF
      clustering and regulatory dynamics.

PMID- 29187153
TI  - Similar, but different: structurally related azelaic acid and hexanoic acid
      trigger differential metabolomic and transcriptomic responses in tobacco cells.
AB  - BACKGROUND: Plants respond to various stress stimuli by activating an enhanced
      broad-spectrum defensive ability. The development of novel resistance inducers
      represents an attractive, alternative crop protection strategy. In this regard,
      hexanoic acid (Hxa, a chemical elicitor) and azelaic acid (Aza, a natural
      signaling compound) have been proposed as inducers of plant defense, by means of
      a priming mechanism. Here, we investigated both the mode of action and the
      complementarity of Aza and Hxa as priming agents in Nicotiana tabacum cells in
      support of enhanced defense. RESULTS: Metabolomic analyses identified signatory
      biomarkers involved in the establishment of a pre-conditioned state following Aza
      and Hxa treatment. Both inducers affected the metabolomes in a similar manner and
      generated common biomarkers: caffeoylputrescine glycoside, cis-5-caffeoylquinic
      acid, feruloylglycoside, feruloyl-3-methoxytyramine glycoside and feruloyl-3
      methoxytyramine conjugate. Subsequently, quantitative real time-PCR was used to
      investigate the expression of inducible defense response genes: phenylalanine
      ammonia lyase, hydroxycinnamoyl CoA quinate transferase and hydroxycinnamoyl
      transferase to monitor activation of the early phenylpropanoid pathway and
      chlorogenic acids metabolism, while ethylene response element-binding protein,
      small sar1 GTPase, heat shock protein 90, RAR1, SGT1, non-expressor of PR genes 1
      and thioredoxin were analyzed to report on signal transduction events.
      Pathogenesis-related protein 1a and defensin were quantified to investigate the
      activation of defenses regulated by salicylic acid and jasmonic acid
      respectively. The qPCR results revealed differential expression kinetics and, in
      general (except for NPR1, Thionin and PR1a), the relative gene expression ratios
      observed in the Hxa-treated cells were significantly greater than the expression
      observed in the cells treated with Aza. CONCLUSIONS: The results indicate that
      Aza and Hxa have a similar priming effect through activation of genes involved in
      the establishment of systemic acquired resistance, associated with enhanced
      synthesis of hydroxycinnamic acids and related conjugates.

PMID- 29187154
TI  - Thymoma with acute gastric volvulus: a case report.
AB  - BACKGROUND: Acute gastric volvulus (GV) is a rare disease with high mortality
      rate often associated with anatomic abnormalities. Thymoma is the most common
      neoplasm located in the anterior mediastinum. There is no reported relationship
      between thymoma and GV. Here we reported a case of thymoma with initial symptom
      of acute gastric volvulus. CASE PRESENTATION: A 43-year-old man complained of
      postprandial abdominal pain, nausea and vomiting. Acute gastric volvulus was
      diagnosed by chest radiograph, upper digestive tract radiograph and CT scan;
      later type B3 thymoma was diagnosed by biopsy of mediastinal mass. We inferred
      that gastric volvulus was secondary to thymoma due to phrenic nerve palsy. The
      patient was treated with endoscopic de-rotation. Further radiotherapy and
      chemotherapy were given. During treatments, GV still occurred with less severity
      and a reduced frequency of approximately every three to four months. CONCLUSION:
      We report the first case of thymoma initially presented with acute GV. We suspect
      a pathological mechanism related to the phrenic nerve palsy. This case indicates
      that thymoma may present alongside rare acute GV.

PMID- 29187155
TI  - Risk score for first-screening of prevalent undiagnosed chronic kidney disease in
      Peru: the CRONICAS-CKD risk score.
AB  - BACKGROUND: Chronic Kidney Disease (CKD) represents a great burden for the
      patient and the health system, particularly if diagnosed at late stages.
      Consequently, tools to identify patients at high risk of having CKD are needed,
      particularly in limited-resources settings where laboratory facilities are
      scarce. This study aimed to develop a risk score for prevalent undiagnosed CKD
      using data from four settings in Peru: a complete risk score including all
      associated risk factors and another excluding laboratory-based variables.
      METHODS: Cross-sectional study. We used two population-based studies: one for
      developing and internal validation (CRONICAS), and another (PREVENCION) for
      external validation. Risk factors included clinical- and laboratory-based
      variables, among others: sex, age, hypertension and obesity; and lipid profile,
      anemia and glucose metabolism. The outcome was undiagnosed CKD: eGFR < 60
      ml/min/1.73m2. We tested the performance of the risk scores using the area under
      the receiver operating characteristic (ROC) curve, sensitivity, specificity,
      positive/negative predictive values and positive/negative likelihood ratios.
      RESULTS: Participants in both studies averaged 57.7 years old, and over 50% were
      females. Age, hypertension and anemia were strongly associated with undiagnosed
      CKD. In the external validation, at a cut-off point of 2, the complete and
      laboratory-free risk scores performed similarly well with a ROC area of 76.2% and
      76.0%, respectively (P = 0.784). The best assessment parameter of these risk
      scores was their negative predictive value: 99.1% and 99.0% for the complete and
      laboratory-free, respectively. CONCLUSIONS: The developed risk scores showed a
      moderate performance as a screening test. People with a score of >= 2 points
      should undergo further testing to rule out CKD. Using the laboratory-free risk
      score is a practical approach in developing countries where laboratories are not
      readily available and undiagnosed CKD has significant morbidity and mortality.

PMID- 29187156
TI  - Lack of controlled studies investigating the risk of postpartum haemorrhage in
      cesarean delivery after prior use of oxytocin: a scoping review.
AB  - BACKGROUND: Postpartum haemorrhage (PPH) is a major cause of maternal mortality
      and morbidity worldwide. Experimental and clinical studies indicate that
      prolonged oxytocin exposure in the first or second stage of labour may be
      associated with impaired uterine contractility and an increased risk of atonic
      PPH. Therefore, particularly labouring women requiring cesarean delivery
      constitute a subset of patients that may exhibit an unpredictable response to
      oxytocin. We mapped the evidence for comparative studies investigating the
      hypothesis whether the risk for PPH is increased in women requiring cesarean
      section after induction or augmentation of labour. METHODS: We performed a
      systematic literature search for clinical trials in Medline, Embase, Web of
      Science, and the Cochrane Library (May 2016). Additionally we searched for
      ongoing or unpublished trials in clinicaltrials.gov and the WHO registry
      platform. We identified a total of 36 controlled trials investigating the
      exogenous use of oxytocin in cesarean section. Data were extracted for study key
      characteristics and the current literature literature was described narratively.
      RESULTS: Our evidence map shows that the majority of studies investigating the
      outcome PPH focused on prophylactic oxytocin use compared to other uterotonic
      agents in the third stage of labour. Only 2 dose-response studies investigated
      the required oxytocin dose to prevent uterine atony after cesarean delivery for
      labour arrest. These studies support the hypotheses that labouring women exposed
      to exogenous oxytocin require a higher oxytocin dose after delivery than non
      labouring women to prevent uterine atony after cesarean section. However, the
      study findings are flawed by limitations of the study design as well as the
      outcome selection. No clinical trial was identified that directly compared
      exogenous oxytocin versus no oxytocin application before intrapartum cesarean
      delivery. CONCLUSION: Despite some evidence from dose-response studies that the
      use of oxytocin may increase the risk for PPH in intrapartum cesarean delivery,
      current research has not investigated the prepartal application of oxytocin in
      well controlled clinical trials. It was striking that most studies on exogenous
      oxytocin are focused on PPH prophylaxis in the third stage of labour without
      differing between the indications of cesarean section and hence the prepartal
      oxytocin status.

PMID- 29187158
TI  - Associations of intimate partner violence with postnatal health practices in
      Bihar, India.
AB  - BACKGROUND: Reducing neonatal mortality is a global priority, and improvements in
      postnatal health (PNH) practices in India are needed to do so. Intimate partner
      violence (IPV) may be associated with PNH practices, but little research has
      assessed this relationship. METHODS: A cross-sectional analysis of data from a
      representative household sample of mothers of neonates 0-11 months old in Bihar,
      India was conducted. The relationship between lifetime IPV experience (physical
      violence only, sexual violence only, or both physical and sexual violence) and
      PNH practices [clean cord care, kangaroo mother care, early initiation of
      breastfeeding (EIBF), delayed bathing, receipt of a postnatal care visit,
      exclusive breastfeeding, and current post-partum contraceptive use] was assessed
      using multivariate logistic regression. RESULTS: Over 45% of the 10,469 mothers
      experienced IPV in their lifetime. The three types of IPV experiences
      differentially related to PNH practices. Adjusted analyses revealed that compared
      to those who had never experienced IPV, women who experienced physical violence
      only (29.0%) had higher odds of skin-to-skin care (AOR = 1.67, 95% CI = 1.42,
      1.96) and delayed bathing (AOR = 1.19, 95% CI = 1.03, 1.37), but lower odds of
      EIBF (AOR = 0.81, 95% CI = 0.70, 0.93) and exclusive breastfeeding (AOR = 0.83,
      95% CI = 0.71, 0.96). Mothers who had experienced sexual violence only (2.3%) had
      lower odds of practicing EIBF (AOR = 0.52, 95% CI = 0.36, 0.76). Those who had
      both experiences of physical and sexual violence (14.0%) had increased odds of
      postpartum modern contraceptive use (AOR = 1.35, 95% CI = 1.07, 1.71) and lower
      odds of delayed bathing (AOR = 0.76, 95% CI = 0.63, 0.91). CONCLUSIONS: The
      results of this study found differing patterns of vulnerability to poor PNH
      practices depending on the type of IPV experienced. Efforts to increase access to
      health services for women experiencing IPV and to integrate IPV intervention into
      such service may increase PNH practices, and as a result, reduce neonatal
      mortality.

PMID- 29187157
TI  - CONSORT to community: translation of an RCT to a large-scale community
      intervention and learnings from evaluation of the upscaled program.
AB  - BACKGROUND: Translation encompasses the continuum from clinical efficacy to
      widespread adoption within the healthcare service and ultimately routine clinical
      practice. The Parenting, Eating and Activity for Child Health (PEACHTM) program
      has previously demonstrated clinical effectiveness in the management of child
      obesity, and has been recently implemented as a large-scale community
      intervention in Queensland, Australia. This paper aims to describe the
      translation of the evaluation framework from a randomised controlled trial (RCT)
      to large-scale community intervention (PEACHTM QLD). Tensions between RCT
      paradigm and implementation research will be discussed along with lived
      evaluation challenges, responses to overcome these, and key learnings for future
      evaluation conducted at scale. METHODS: The translation of evaluation from
      PEACHTM RCT to the large-scale community intervention PEACHTM QLD is described.
      While the CONSORT Statement was used to report findings from two previous RCTs,
      the REAIM framework was more suitable for the evaluation of upscaled delivery of
      the PEACHTM program. Evaluation of PEACHTM QLD was undertaken during the project
      delivery period from 2013 to 2016. RESULTS: Experiential learnings from
      conducting the evaluation of PEACHTM QLD to the described evaluation framework
      are presented for the purposes of informing the future evaluation of upscaled
      programs. Evaluation changes in response to real-time changes in the delivery of
      the PEACHTM QLD Project were necessary at stages during the project term. Key
      evaluation challenges encountered included the collection of complete evaluation
      data from a diverse and geographically dispersed workforce and the systematic
      collection of process evaluation data in real time to support program changes
      during the project. CONCLUSIONS: Evaluation of large-scale community
      interventions in the real world is challenging and divergent from RCTs which are
      rigourously evaluated within a more tightly-controlled clinical research setting.
      Constructs explored in an RCT are inadequate in describing the enablers and
      barriers of upscaled community program implementation. Methods for data
      collection, analysis and reporting also require consideration. We present a
      number of experiential reflections and suggestions for the successful evaluation
      of future upscaled community programs which are scarcely reported in the
      literature. TRIALS REGISTRATION: PEACHTM QLD was retrospectively registered with
      the Australian New Zealand Clinical Trials Registry on 28 February 2017
      (ACTRN12617000315314).

PMID- 29187160
TI  - Nephrolithiasis and risk of hypertension: a meta-analysis of observational
      studies.
AB  - BACKGROUND: Observational studies have demonstrated an association between
      nephrolithiasis and hypertension. The aim of this meta-analysis was to summarize
      all available evidence. METHODS: PubMed, EMBASE, the Cochrane Central Register of
      Controlled Trials databases, and the reference lists of relevant articles were
      searched to identify observational studies that reported study-specific risk
      estimates comparing the risk of hypertension in patients with nephrolithiasis. We
      used a random-effect model to pool the study-specific risk estimates. We also
      assessed the potential heterogeneity by subgroup analyses, meta-regression
      analyses, and sensitivity analyses. RESULTS: A total of 7 articles including 9
      studies (n = 313,222 participants) were eventually identified in this meta
      analysis. In comparison with the patients who did not have nephrolithiasis,
      nephrolithiasis significantly increased the risk of hypertension (OR, 1.43; 95%
      CI, 1.30-1.56), with significant heterogeneity between these studies (I 2 =
      83.5%, P <0.001). The heterogeneity reduced in subgroups of cohort studies, USA,
      large sample size trials, men, and adjustment for confounding factors >= 5.
      Sensitivity analysis further demonstrated the results to be robust. CONCLUSIONS:
      Nephrolithiasis is associated with increased risk of hypertension. Future
      randomized, high-quality clinical trials are encouraged to definitively clarify
      the relationship between nephrolithiasis and hypertension, which may influence
      clinical management and primary prevention of hypertension in nephrolithiasis
      patients.

PMID- 29187159
TI  - Decision tree for accurate infection timing in individuals newly diagnosed with
      HIV-1 infection.
AB  - BACKGROUND: There is today no gold standard method to accurately define the time
      passed since infection at HIV diagnosis. Infection timing and incidence
      measurement is however essential to better monitor the dynamics of local
      epidemics and the effect of prevention initiatives. METHODS: Three methods for
      infection timing were evaluated using 237 serial samples from documented
      seroconversions and 566 cross sectional samples from newly diagnosed patients:
      identification of antibodies against the HIV p31 protein in INNO-LIA, SediaTM BED
      CEIA and SediaTM LAg-Avidity EIA. A multi-assay decision tree for infection
      timing was developed. RESULTS: Clear differences in recency window between BED
      CEIA, LAg-Avidity EIA and p31 antibody presence were observed with a switch from
      recent to long term infection a median of 169.5, 108.0 and 64.5 days after
      collection of the pre-seroconversion sample respectively. BED showed high
      reliability for identification of long term infections while LAg-Avidity is
      highly accurate for identification of recent infections. Using BED as initial
      assay to identify the long term infections and LAg-Avidity as a confirmatory
      assay for those classified as recent infection by BED, explores the strengths of
      both while reduces the workload. The short recency window of p31 antibodies
      allows to discriminate very early from early infections based on this marker. BED
      recent infection results not confirmed by LAg-Avidity are considered to reflect a
      period more distant from the infection time. False recency predictions in this
      group can be minimized by elimination of patients with a CD4 count of less than
      100 cells/mm3 or without no p31 antibodies. For 566 cross sectional sample the
      outcome of the decision tree confirmed the infection timing based on the results
      of all 3 markers but reduced the overall cost from 13.2 USD to 5.2 USD per
      sample. CONCLUSIONS: A step-wise multi assay decision tree allows accurate timing
      of the HIV infection at diagnosis at affordable effort and cost and can be an
      important new tool in studies analyzing the dynamics of local epidemics or the
      effects of prevention strategies.

PMID- 29187161
TI  - Does the oviparity-viviparity transition alter the partitioning of yolk in
      embryonic snakes?
AB  - BACKGROUND: The oviparity-viviparity transition is a major evolutionary event,
      likely altering the reproductive process of the organisms involved. Residual
      yolk, a portion of yolk remaining unutilized at hatching or birth as parental
      investment in care, has been investigated in many oviparous amniotes but remained
      largely unknown in viviparous species. Here, we used data from 20 (12 oviparous
      and 8 viviparous) species of snakes to see if the oviparity-viviparity transition
      alters the partitioning of yolk in embryonic snakes. We used ANCOVA to test
      whether offspring size, mass and components at hatching or birth differed between
      the sexes in each species. We used both ordinary least squares and phylogenetic
      generalized least squares regressions to test whether relationships between
      selected pairs of offspring components were significant. We used phylogenetic
      ANOVA to test whether offspring components differed between oviparous and
      viviparous species and, more specifically, the hypothesis that viviparous snakes
      invest more in the yolk as parental investment in embryogenesis to produce more
      well developed offspring that are larger in linear size. RESULTS: In none of the
      20 species was sex a significant source of variation in any offspring component
      examined. Newborn viviparous snakes on average contained proportionally more
      water and, after accounting for body dry mass, had larger carcasses but smaller
      residual yolks than did newly hatched oviparous snakes. The rates at which
      carcass dry mass (CDM) and fat body dry mass (FDM) increased with residual yolk
      dry mass (YDM) did not differ between newborn oviparous and viviparous snakes.
      Neither CDM nor FDM differed between newborn oviparous and viviparous snakes
      after accounting for YDM. CONCLUSIONS: Our results are not consistent with the
      hypothesis that the partitioning of yolk between embryonic and post-embryonic
      stages differs between snakes that differ in parity mode, but instead show that
      the partitioning of yolk in embryonic snakes is species-specific or
      phylogenetically related. We conclude that the oviparity-viviparity transition
      does not alter yolk partitioning in embryonic snakes.

PMID- 29187163
TI  - Daptomycin treatment in patients with resistant staphylococcal periprosthetic
      joint infection.
AB  - BACKGROUND: Resistant staphylococcal organisms remain a serious problem in the
      treatment of periprosthetic joint infection (PJI). Higher failure rates have been
      reported when vancomycin was used. The purpose of this study was to assess the
      clinical dosage, effect, and safety of daptomycin in patients with resistant
      staphylococcal PJI. METHODS: We retrospectively enrolled patients with hip or
      knee PJI who were treated with daptomycin in our institution (n = 16) from
      January 2013 to December 2014 with a minimum follow-up of 2 years. The patients
      received daptomycin when glycopeptide could not be used due to multiple
      resistance, any adverse reaction, chronic kidney disease stage 3 or worse, and
      previous treatment failure with glycopeptide or empirical therapy. RESULTS: These
      patients received daptomycin at a median dose of 8.3 mg/kg per day for a median
      duration of 14 days. The overall treatment success rate was 87.5% (14 of 16
      cases) after a median follow-up period of 27 months. In the subgroups of acute
      and chronic PJI, the success rate was 80% and 91%, respectively. One patient
      developed asymptomatic transient serum aspartate transaminase (AST) elevation. No
      severe side effects such as myositis, acute renal failure due to rhabdomyolysis
      or eosinophilic pneumonia were found in our series. CONCLUSION: Relatively high
      daptomycin doses combined with adequate surgical intervention were effective in
      treating resistant staphylococcal PJI. Daptomycin is an option worthy of
      consideration in PJI patients for whom glycopeptide treatment is unsuitable.
      Further prospective randomized comparative study is needed in the future.

PMID- 29187162
TI  - Isolation and characterization of a new naturally immortalized human breast
      carcinoma cell line, KAIMRC1.
AB  - BACKGROUND: Breast cancer is one of the most common cancer and a leading cause of
      death in women. Up to date the most commonly used breast cancer cell lines are
      originating from Caucasians or Afro-Americans but rarely cells are being derived
      from other ethnic groups. Here we describe for the first time the establishment
      of a naturally transformed breast cancer cell line, KAIMRC1 from an Arab woman of
      age 62 suffering from stage IIB breast cancer (T2N1M0). Moreover, we have
      characterized these cells for the biological and molecular markers, induction of
      MAPK pathways as well as its response to different commercially available drugs
      and compounds. METHODS: Breast cancer tissue sections were minced and cultured in
      media for several weeks. KAIMRC1 cells were successfully isolated from one of the
      primary breast tumor tissue cultures without any enzymatic digestion. To study
      the growth characteristics of the cells, wound healing assay, clonogenic assay,
      cell proliferation assays and live cell time-lapse microscopy was performed.
      Karyotyping, Immunophenotyping and molecular pathway specific compound treatment
      was also performed. A selective breast cancer gene expression panel was used to
      identify genes involved in the signal transduction dysregulation and malfunction
      of normal biological processes during breast carcinogenesis. RESULTS: These cells
      are ER/PR-positive and HER2-negative. The epithelial nature of these cells was
      confirmed by flow cytometry analysis using epithelial cell markers. They are
      cuboidal in shape and relatively smaller in size as compared to established cell
      lines, MCF-7, MDA MB-231 and the normal breast cell line, MCF-10A. In normal cell
      culture conditions these cells showed the capability of growing both in monolayer
      as well as in 3-D conformation. They showed a doubling time in vitro of
      approximately 24 h. They exhibit a modal karyotype of 58-63,X with abnormalities
      in a couple of chromosomes. KAIMRC1 cells were found to be more responsive to
      drug treatment in vitro in comparison to the established MDA MB-231 and MCF-7
      cell lines. CONCLUSIONS: In conclusion we have isolated and characterized a new
      naturally immortalized breast cell line, KAIMRC1 with a potential to play a key
      role in opening up novel avenues towards the understanding of breast carcinoma.

PMID- 29187164
TI  - Depression stigma and migration - results of a survey from Germany.
AB  - BACKGROUND: There are barely any studies focusing on migration in relation to
      mental illness stigma. We explore present attitudes regarding depression among
      migrants (either born in Germany or born abroad) and non-migrants in Germany,
      drawing upon three components of public stigma: stereotypes, emotional reactions
      and desire for social distance. Furthermore, differences in self-stigma of
      depression between the two groups are analyzed. METHODS: Analyses are based on a
      representative telephone survey (N = 2013) in Germany. Respondents were presented
      with a vignette depicting either someone from Turkey or from Germany affected by
      depression, followed by questions on stereotypes, emotional reactions and desire
      for social distance. The (anticipated) self-stigma of depression was also
      assessed. Analyses of variance tested for differences between migrant and non
      migrant respondents, stratified by migrant status in the vignette. RESULTS:
      Regarding the depression vignette depicting a non-migrant, there were only few
      differences between subgroups. However, when presented with a vignette describing
      someone from Turkey, respondents with migrant background who were foreign-born
      expressed greater stigmatizing attitudes, e.g. when it comes to stereotypes or
      desire for social distance. Furthermore, this subsample displayed higher levels
      of self-stigma of depression, especially regarding the ascription of own
      responsibility. CONCLUSIONS: The results underline the need to incorporate
      migration status/ethnicity in stigma research. Differences in attitudes as well
      as in (anticipated) self-stigma of depression identify foreign-born migrants in
      Germany as important target groups for tailored anti-stigma interventions, which
      need to consider diverse cultural backgrounds.

PMID- 29187165
TI  - ImageJ2: ImageJ for the next generation of scientific image data.
AB  - BACKGROUND: ImageJ is an image analysis program extensively used in the
      biological sciences and beyond. Due to its ease of use, recordable macro
      language, and extensible plug-in architecture, ImageJ enjoys contributions from
      non-programmers, amateur programmers, and professional developers alike. Enabling
      such a diversity of contributors has resulted in a large community that spans the
      biological and physical sciences. However, a rapidly growing user base, diverging
      plugin suites, and technical limitations have revealed a clear need for a
      concerted software engineering effort to support emerging imaging paradigms, to
      ensure the software's ability to handle the requirements of modern science.
      RESULTS: We rewrote the entire ImageJ codebase, engineering a redesigned plugin
      mechanism intended to facilitate extensibility at every level, with the goal of
      creating a more powerful tool that continues to serve the existing community
      while addressing a wider range of scientific requirements. This next-generation
      ImageJ, called "ImageJ2" in places where the distinction matters, provides a host
      of new functionality. It separates concerns, fully decoupling the data model from
      the user interface. It emphasizes integration with external applications to
      maximize interoperability. Its robust new plugin framework allows everything from
      image formats, to scripting languages, to visualization to be extended by the
      community. The redesigned data model supports arbitrarily large, N-dimensional
      datasets, which are increasingly common in modern image acquisition. Despite the
      scope of these changes, backwards compatibility is maintained such that this new
      functionality can be seamlessly integrated with the classic ImageJ interface,
      allowing users and developers to migrate to these new methods at their own pace.
      CONCLUSIONS: Scientific imaging benefits from open-source programs that advance
      new method development and deployment to a diverse audience. ImageJ has
      continuously evolved with this idea in mind; however, new and emerging scientific
      requirements have posed corresponding challenges for ImageJ's development. The
      described improvements provide a framework engineered for flexibility, intended
      to support these requirements as well as accommodate future needs. Future efforts
      will focus on implementing new algorithms in this framework and expanding
      collaborations with other popular scientific software suites.

PMID- 29187167
TI  - High ocular CMV copies and mismatched receipts may predict poor visual prognosis
      in CMV retinitis patients following allogeneic haematopoietic stem cell
      transplantation.
AB  - BACKGROUND: To summarize the clinical characteristics and potential factors
      affecting the visual outcomes in patients with cytomegalovirus retinitis
      following allogeneic haematopoietic stem cell transplantation (HSCT). METHODS:
      This retrospective study enrolled 12 patients (19 eyes) with cytomegalovirus
      retinitis after HSCT at Guangzhou First People's Hospital in China between
      January 2013 and December 2014. Demographic and clinical characteristics, ocular
      manifestations and visual outcomes were evaluated by reviewing medical records at
      the Departments of Hematology and Ophthalmology. All patients were followed up at
      least 6 months after stopping antiviral therapy. The visual outcome was defined
      as improvement, stabilization and deterioration. RESULTS: The subjects were
      composed of 7 human leucocyte antigen-matched and 5 mismatched receipts. All
      patients received combined systemic and intravitreous antiviral therapy. Eleven
      eyes gained improved or stabilized visual acuity, while 8 eyes suffered
      deterioration. Eyes with cytomegalovirus load less than 1 * 104 copies/ml in
      vitreous accounted for higher rate in eyes with good visual prognosis than those
      with cytomegalovirus copies above 1 * 104 copies/ml (52.63% vs 5.26%, P < 0.001).
      Human leucocyte antigen-matched receipts gained better visual prognosis than
      those mismatched ones (47.37% vs10.53%, P < 0.05). The virus types,
      cytomegalovirus peak in the blood, involved retinal zone and size had no
      influence on the visual outcomes (all P > 0.05). CONCLUSIONS: High ocular
      cytomegalovirus copies and mismatched receipts may be potential adverse factors
      affecting visual outcomes in cytomegalovirus retinitis patients following
      allogeneic HSCT.

PMID- 29187166
TI  - What is the safest mode of delivery for extremely preterm cephalic/non-cephalic
      twin pairs? A systematic review and meta-analyses.
AB  - BACKGROUND: Given the controversy around mode of delivery, our objective was to
      assess the evidence regarding the safest mode of delivery for actively
      resuscitated extremely preterm cephalic/non-cephalic twin pairs before 28 weeks
      of gestation. METHODS: We searched Cochrane CENTRAL, MEDLINE, EMBASE and 
      http://clinicaltrials.gov from January 1994 to January 2017. Two reviewers
      independently screened titles, abstracts and full text articles, extracted data
      and assessed risk of bias. We included randomized controlled trials and
      observational studies. Our primary outcome was a composite of neonatal death (<28
      days of life) and severe brain injury in survivors (intraventricular hemorrhage
      grade >= 3 or periventricular leukomalacia). We performed random-effects meta
      analyses, generating odds ratios with 95% confidence intervals for the first and
      second twin separately, and for both twins together. We assessed the risk of bias
      using a modified Newcastle Ottawa Scale (NOS) for observational studies and used
      Grading of Recommendations Assessment, Development and Evaluation approach
      (GRADE). RESULTS: Our search generated 2695 articles, and after duplicate
      removal, we screened 2051 titles and abstracts, selecting 113 articles for full
      text review. We contacted 36 authors, and ultimately, three observational studies
      met our inclusion criteria. In cephalic/non-cephalic twin pairs delivered by
      caesarean section compared to vaginal birth at 24+0-27+6 weeks the odds ratio for
      our composite outcome of neonatal death and severe brain injury for the cephalic
      first twin was 0.35 (95% CI 0.00-92.61, two studies, I2 = 76%), 1.69 for the non
      cephalic second twin (95% CI 0.04-72.81, two studies, I2 = 55%) and 0.83 for both
      twins (95% CI 0.05-13.43, two studies, I2 = 56%). According to the modified
      Newcastle Ottawa Scale we assessed individual study quality as being at high risk
      of bias and according to GRADE the overall evidence for our primary outcomes was
      very low. CONCLUSION: Our systematic review on the safest mode of delivery for
      extremely preterm cephalic/non-cephalic twin pairs found very limited existing
      evidence, without significant differences in neonatal death and severe brain
      injury by mode of delivery.

PMID- 29187168
TI  - Spasm and flexion-relaxation phenomenon response to large lifting load during the
      performance of a trunk flexion-extension exercise.
AB  - BACKGROUND: The flexion relaxation phenomenon (FRP) has been widely investigated.
      Nevertheless, no study has been reported on the FRP as well as spasm response to
      large lifting load. The aim of this study was to evaluate the effect of large
      lifting load on the FRP response and spasm during execution of a flexion
      extension exercise. METHODS: Twenty-two healthy male university students without
      low back pain history participated this study. Subjects randomly performed three
      trials of trunk flexion-extension cycles of 5 s flexion and 5 s extension in each
      of 4 conditions (three large lifting loads of 15, 20 and 25 kg and one lifting
      load of 0 kg for comparison). Surface EMG from bilateral erector spinae was
      recorded during the performance of a trunk anterior flexion-extension exercise.
      The relaxation phase was determined through the onset of electromyography (EMG)
      signals. Spasm was evaluated in the relaxation period. The mean normalized
      electromyography (NEMG) was derived from the raw EMG. RESULTS: Spasm was observed
      in more than 45% of the individuals and the intensity of muscle activation was
      increased by more than 78% in the relaxation phase. CONCLUSIONS: A large lifting
      load could lead to a high prevalence of spasms as well as a high intensity of
      muscle activations on erector spinae muscle in the relaxation period, which may
      be associated with the development of low back disorder during the performance of
      a flexion-extension exercise.

PMID- 29187169
TI  - The accuracy of the auto-stop function of different endodontic devices in
      detecting the apical constriction.
AB  - BACKGROUND: Electronic apex locators (EALs) are modern devices used to determine
      the working length during root canal preparation. The newest endodontic motors
      provide an integrated EAL with auto-stop function to prevent instrumentation
      beyond the predefined working length during rotary root canal preparation. The
      aim of this study was to compare the accuracy of the auto-stop function of the
      VDW.Gold RECIPROC motor (VDW, Munich, Germany), the EndoPilot motor (Schlumbohm,
      Brokstedt, Germany) and the manual measurement with Raypex 6 (VDW, Munich,
      Germany) to detect the apical constriction (AC). METHODS: Ninety human teeth were
      chosen and randomly assigned to three experimental groups (30 teeth each):
      VDW.Gold RECIPROC motor continuous measuring (RCM), EndoPilot continuous
      measuring (ECM) and Raypex 6 manual measuring (RMM). When the measurement file
      reached the AC, the file was fixed in the tooth. The tooth was embedded in
      acrylic resin and the root tip was exposed, so that the histologic structure of
      the root canal and the file tip was visible for microscopic analysis. Afterwards,
      the distance of the file tip to the AC (DAC) was automatically computed with a
      specially developed software tool. RESULTS: The mean DAC were -13.18 MUm (SD
      88.46 MUm) for RMM, -22.70 MUm (SD 91.57 MUm) for RCM and 18.74 MUm (SD 88.11
      MUm) for ECM. The differences were not statistically significant (P = 0.181). The
      rates for instrumentation beyond the AC were not statistically different (Chi2 =
      4.753, p = 0.096). CONCLUSIONS: All measurement methods showed a high accuracy in
      detecting the AC. The auto-stop function of these endodontic motors is a reliable
      addition to the endodontic armamentarium.

PMID- 29187170
TI  - Correction to: The Cedar Project: Using Indigenous-specific determinants of
      health to predict substance use among young pregnant-involved Indigenous women in
      Canada.
AB  - After publication of the original article (1) it was noted that the title of this
      manuscript was incorrect. The title presently reads "The cedar project: using
      indigenous-specific determinants of health to predict substance use among young
      pregnant-involved aboriginal women" but should read "The Cedar Project: Using
      Indigenous-specific determinants of health to predict substance use among young
      pregnant-involved Indigenous women in Canada".

PMID- 29187171
TI  - Antibiotic duration and changes in FEV1 are not associated with time until next
      exacerbation in adult cystic fibrosis: a single center study.
AB  - BACKGROUND: Pulmonary exacerbations (PEx) are a major driver of morbidity and
      mortality in cystic fibrosis and reducing their frequency by extending the time
      between them is an important therapeutic goal. Although treatment decisions for
      exacerbations are often made based on dynamic changes in lung function, it is not
      clear if these changes truly impact future exacerbation risk. We analyzed adults
      with chronic Pseudomonas aeruginosa infection to determine whether changes in
      FEV1 or duration of intravenous antibiotic therapy were associated with time to
      the next pulmonary exacerbation. METHODS: Medical records and Cystic Fibrosis
      Foundation Patient Registry data were examined retrospectively to assess whether
      various patient-specific demographic factors and exacerbation-specific
      characteristics were associated with time until next exacerbation using the
      Andersen-Gill model in order to control for previous exacerbation frequency
      history. RESULTS: We examined 59 patients with 221 CF pulmonary exacerbations
      over a 3-year study period. Mean age was 28.2 years and mean baseline FEV1 was
      62% predicted. In our univariable model, fall in FEV1 at onset of exacerbation
      (median absolute -3% predicted change), recovery of FEV1 with treatment (median
      absolute +3% predicted change) and duration of IV antibiotics (median 16 days)
      were not associated with time to next exacerbation (median 93.5 days).
      Paradoxically each one-year increase in age was associated with a reduction in
      hazard of PEx by 3% (HR 0.97, P = 0.03, 95% CI 0.95-1.00). CONCLUSIONS: FEV1 drop
      and recovery associated with onset and treatment of a CF pulmonary exacerbation
      or duration of intravenous antibiotics were not predictive of time until next
      exacerbation. Our finding that older age may be associated with decreased hazard
      of exacerbation is likely due to a healthy survivor effect and should be
      controlled for in clinical trials of pulmonary exacerbations.

PMID- 29187172
TI  - Investing in the use of a checklist during differential diagnoses consideration:
      what's the trade-off?
AB  - BACKGROUND: A key challenge clinicians face when considering differential
      diagnoses is whether the patient data have been adequately collected.
      Insufficient data may inadvertently lead to premature closure of the diagnostic
      process. This study aimed to test the hypothesis that the application of a
      mnemonic checklist helps to stimulate more patient data collection, thus leading
      to better diagnostic consideration. METHODS: A total of 88 final year medical
      students were assigned to either an educational intervention group or a control
      group in a non-equivalent group post-test only design. Participants in the
      intervention group received a tutorial on the use of a mnemonic checklist aimed
      to minimize cognitive errors in clinical decision-making. Two weeks later, the
      participants in both groups were given a script concordance test consisting of 10
      cases, with 3 items per case, to assess their clinical decisions when additional
      data are given in the case scenarios. RESULTS: The Mann-Whitney U-test performed
      on the total scores from both groups showed no statistical significance (U = 792,
      z = -1.408, p = 0.159). When comparisons were made for the first half and the
      second half of the SCT, it was found that participants in the intervention group
      performed significantly better than participants in the control group in the
      first half of the test, with median scores of 9.15 (IQR 8.00-10.28) vs. 8.18 (IQR
      7.16-9.24) respectively, U = 642.5, z = -2.661, p = 0.008. No significant
      difference was found in the second half of the test, with the median score of
      9.58 (IQR 8.90-10.56) vs. 9.81 (IQR 8.83-11.12) for the intervention group and
      control group respectively (U = 897.5, z = -0.524, p = 0.60). CONCLUSION:
      Checklist use in differential diagnoses consideration did show some benefit.
      However, this benefit seems to have been traded off by the time and effort in
      using it. More research is needed to determine whether this benefit could be
      translated into clinical practice after repetitive use.

PMID- 29187173
TI  - Anti-inflammatory evaluation of the methanolic extract of Taraxacum officinale in
      LPS-stimulated human umbilical vein endothelial cells.
AB  - BACKGROUND: Atherosclerosis is a chronic vascular inflammatory disease. Since
      even low-level endotoxemia constitutes a powerful and independent risk factor for
      the development of atherosclerosis, it is important to find therapies directed
      against the vascular effects of endotoxin to prevent atherosclerosis. Taraxacum
      officinale (TO) is used for medicinal purposes because of its choleretic,
      diuretic, antioxidative, anti-inflammatory, and anti-carcinogenic properties, but
      its anti-inflammatory effect on endothelial cells has not been established.
      METHODS: We evaluated the anti-inflammatory activity of TO filtered methanol
      extracts in LPS-stimulated human umbilical vein endothelial cells (HUVECs) by
      monocyte adhesion and western blot assays. HUVECs were pretreated with 100 MUg/ml
      TO for 1 h and then incubated with 1 MUg/ml LPS for 24 h. The mRNA and protein
      expression levels of the targets (pro-inflammatory cytokines and adhesion
      molecules) were analyzed by real-time PCR and western blot assays. We also
      preformed HPLC analysis to identify the components of the TO methanol extract.
      RESULTS: The TO filtered methanol extracts dramatically inhibited LPS-induced
      endothelial cell-monocyte interactions by reducing vascular cell adhesion
      molecule-1 and monocyte chemoattractant protein-1, and pro-inflammatory cytokine
      expression. TO suppressed the LPS-induced nuclear translocation of NF-kappaB,
      whereas it did not affect MAPK activation. CONCLUSIONS: Our findings demonstrated
      that methanol extracts of TO could attenuate LPS-induced endothelial cell
      activation by inhibiting the NF-kappaB pathway. These results indicate the
      potential clinical benefits and applications of TO for the prevention of vascular
      inflammation and atherosclerosis.

PMID- 29187174
TI  - Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic
      based molecular profiling.
AB  - BACKGROUND: Transcriptomic profiling of breast tumors provides opportunity for
      subtyping and molecular-based patient stratification. In diagnostic applications
      the specimen profiled should be representative of the expression profile of the
      whole tumor and ideally capture properties of the most aggressive part of the
      tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at
      molecular, genomic and in phenotypic level, which can arise during tumor
      evolution. Currently it is not established to what extent a random sampling
      approach may influence molecular breast cancer diagnostics. METHODS: In this
      study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5
      pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular
      subtype and transcriptomic grade for all tumor pieces and analysed to what extent
      pieces originating from the same tumors are concordant or discordant with each
      other. Additionally, we validated our finding in an independent cohort consisting
      of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled
      using microarray technique. Exome sequencing was also performed on this cohort,
      to investigate the extent of intra-tumor genomic heterogeneity versus the intra
      tumor molecular subtype classifications. RESULTS: Molecular subtyping was
      consistent in 11 out of 12 tumors and transcriptomic grade assignments were
      consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed
      consistent subtypes in four out of six patients in this cohort 2. Interestingly,
      we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but
      not in their molecular subtype classifications. CONCLUSIONS: Our results suggest
      that macroscopic intra-tumoral transcriptomic heterogeneity is limited and
      unlikely to have an impact on molecular diagnostics for most patients.

PMID- 29187175
TI  - Standards for permanent tooth emergence in Czech children.
AB  - BACKGROUND: The aim of this study is to develop a population-specific reference
      for permanent tooth emergence among 4-15 years old Czech Republic children. The
      reference derived from this sample population are essential for pediatric dental
      diagnostics, orthodontic treatment planning, as well as anthropological and
      forensic applications. METHODS: In this cross-sectional epidemiological survey,
      dental examinations of 1,370 Czech children (696 girls (50,8%) and 674 boys
      (49,2%), whose parents or legal guardians all signed informed consent forms) from
      11 elementary schools and kindergartens were performed in the classroom. During
      the examination, previously emerged permanent teeth (other than third molars),
      the child's age and gender were recorded. A tooth is defined as having erupted
      when at least any part of the crown penetrates the gingiva, and is clinically
      seen in the oral cavity. A logistic regression model was used to calculate the
      median emergence age per tooth for both genders and the total sample. The data
      was statistically processed (using IBM SPSS Statistics 23) and carried out at a
      deviation level of 0.05. The statistical significance of the differences in the
      emergence of permanent teeth (contralateral, intermaxillary, inter-gender
      differences) was evaluated by the McNemar test. RESULTS: No statistically
      significant differences were observed in the emergence times between right and
      left sides. In addition, mandibular teeth emerged earlier than the corresponding
      maxillary ones (with the exception of the first and second premolars). Permanent
      teeth were found to emerge sooner in girls. Furthermore, the greatest inter
      gender difference was observed in maxillary canines. CONCLUSIONS: The new data
      reported can now be used as standards when assessing permanent tooth emergence of
      Czech children.

PMID- 29187176
TI  - Frequency of DEA 1 antigen in 1037 mongrel and PUREBREED dogs in ITALY.
AB  - BACKGROUND: The prevalence of dog erythrocyte antigen (DEA 1) in canine
      population is approximately 40-60%. Often data are limited to a small number of
      breeds and/or dogs. The aims of this study were to evaluate frequency of DEA 1 in
      a large population of purebred and mongrel dogs including Italian native breeds
      and to recognize a possible association between DEA 1 and breed, sex, and genetic
      and phenotypical/functional classifications of breeds. Frequencies of DEA 1 blood
      group collected from screened/enrolled blood donors and from healthy and sick
      dogs were retrospectively evaluated. The breed and the sex were recorded when
      available. DEA 1 blood typing was assessed by immunocromatographic test on K3EDTA
      blood samples. The prevalence of DEA 1 antigen was statistically related to
      breed, gender, Federation Cynologique Internationale (FCI) and genotypic
      grouping. RESULTS: Sixty-two per cent dogs resulted DEA 1+ and 38% DEA 1-. DEA 1-
      was statistically associated with Dogo Argentino, Dobermann, German Shepherd,
      Boxer, Corso dogs, the molossian dogs, the FCI group 1, 2 and 3 and the genetic
      groups "working dogs" and "mastiff". DEA 1+ was statistically associated with
      Rottweiler, Briquet Griffon Vendeen, Bernese mountain dog, Golden Retriever, the
      hunting breeds, the FCI group 4, 6, 7 and 8 and the genetic groups "scent hounds"
      and "retrievers". No gender association was observed. CONCLUSIONS: Data obtained
      by this work may be clinically useful to drive blood donor enrollment and
      selection among different breeds.

PMID- 29187177
TI  - Work station learning activities: a flexible and scalable instrument for
      integrating across basic subjects in biomedical education.
AB  - BACKGROUND: Establishing innovative teaching programs in biomedical education
      involves dealing with several national and supra-national (i.e. European)
      regulations as well as with new pedagogical and demographic demands. We aimed to
      develop and validate a suitable instrument to integrate activities across
      preclinical years in all Health Science Degrees while meeting requirements of
      national quality agencies. METHODS: The new approach was conceived at two
      different levels: first, we identified potentially integrative units from
      different fields according to national learning goals established for each
      preclinical year (national quality agency regulations). Secondly, we implemented
      a new instrument that combines active methodologies in Work Station Learning
      Activities (WSLA), using clinical scenarios as a guiding common thread to
      instruct students from an integrated perspective. We evaluated students'
      perception through a Likert-type survey of a total of 118 students enrolled in
      the first year of the Bachelor's Degree in Medicine. RESULTS: Our model of
      integrated activities through WSLA is feasible, scalable and manageable with
      large groups of students and a minimum number of instructors, two major
      limitations in many medical schools. Students' perception of WSLA was positive in
      overall terms. Seventy nine percent of participants stated that WSLA sessions
      were more useful than non-integrated activities. Eighty three percent confirmed
      that the WSLA methodology was effective at integrating concepts covered by
      different subjects. CONCLUSIONS: The WSLA approach is a flexible and scalable
      instrument for moving towards integrated curricula, and it can be successfully
      adapted to teach basic subjects in preclinical years of Health Science degrees.
      WSLA can be applied to large groups of students in a variety of contexts or
      environments using clinical cases as connecting threads.

PMID- 29187178
TI  - Jia-Wei-Jiao-Tai-Wan ameliorates type 2 diabetes by improving beta cell function
      and reducing insulin resistance in diabetic rats.
AB  - BACKGROUND: Jia-Wei-Jiao-Tai-Wan (JWJTW), composed of Jiao-Tai-Wan (Cinnamomum
      cassia and Rhizoma coptidis) and other antidiabetic herbs, including Astragalus
      membranaceus, Herba Gynostemmatis, Radix Puerariae Lobatae, Folium Mori and Semen
      Trigonellae, is widely used to treat diabetes and has demonstrated a curative
      effect in the clinic, but the potential mechanism is unknown. This study aimed to
      explore the effects of JWJTW on diabetic rats and to clarify the underlying
      mechanism. METHODS: JWJTW was prepared, and the main components contained in the
      formula were identified by high-performance liquid chromatography (HPLC)
      fingerprint analysis. Diabetic rats induced by streptozotocin (STZ) and a high
      sucrose-high-fat diet were treated with two concentrations of JWJTW (1.025 and
      2.05 g/kg/d) for 100 days. The oral glucose tolerance test (OGTT), insulin
      release test (IRT) and insulin tolerance test (ITT) were performed to measure the
      glycometabolism of the diabetic rats at the end of the treatment period. Blood
      was collected to determine the serum lipid levels of the diabetic rats. Nitric
      oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-px) were detected in pancreas homogenates to analyze the
      oxidative stress in the pancreata of diabetic rats, and the expression levels of
      pancreatic and duodenal homeobox 1 (PDX-1) and insulin in the pancreas were
      tested by Western blot to measure pancreatic islet function. In addition, Western
      blots were used to measure the expression of proteins related to the insulin
      signaling pathway in skeletal muscle of the diabetic rats. RESULTS: The results
      showed that the administration of JWJTW could ameliorate impairments in glucose
      tolerance, insulin release function and insulin tolerance in diabetic rats. JWJTW
      could also dose-dependently reduce serum lipid levels in diabetic rats. JWJTW
      restrained oxidative stress by decreasing the expression of NO and MDA and
      increasing the expression of SOD and GSH-px. JWJTW improved the function of
      pancreatic beta cells by increasing PDX-1 and insulin expression. In addition,
      JWJTW restored the impaired insulin signaling; upregulated phospho-insulin
      receptor (pInsR) expression, insulin receptor substrate (IRS) tyrosine
      phosphorylation, phosphatidylinositol 3-kinase (PI3K) (p85), and glucose
      transporter 4 (GLUT4) expression; and downregulated the serine phosphorylation of
      IRS. CONCLUSIONS: This study suggests that JWJTW can ameliorate type 2 diabetes
      by improving beta cell function and reducing insulin resistance in diabetic rats.

PMID- 29187179
TI  - The learning environment of paediatric interns in South Africa.
AB  - BACKGROUND: South African (SA) paediatric interns (recently qualified medical
      graduates) work in a high disease burdened and resource deficient environment for
      two years, prior to independent practice. Perceptions of this learning
      environment (LE) influences their approaches to training as well as the outcomes
      of this period of development. Obstacles to creating a supportive LE and
      supervisor interaction affects the quality of this training. Measuring
      perceptions of the LE with validated instruments can help inform improvements in
      learning during this crucial period of medical education. METHODS: The aims of
      this study was to determine the psychometric qualities of the Postgraduate
      Hospital Educational Environment Measure (PHEEM) amongst paediatric interns
      across four hospital complexes in South Africa and to measure the LE as perceived
      by both interns and their supervisors. Construct validity was tested using factor
      analysis and internal consistency was measured with Cronbach's alpha. RESULTS: A
      total of 209 interns and 60 supervisors (69% intern response rate) responded to
      the questionnaire. The PHEEM was found to be very reliable with an overall
      Cronbach's alpha of 0.943 and 0.874 for intern and supervisors respectively.
      Factor analysis using a 3-factor solution accounted for 42% of the variance with
      the teaching subscale having the best fit compared with the other sub-scales of
      the original tool. Most interns perceived the learning environment as being more
      positive than negative however, their perceptions differed significantly from
      that of their supervisors. Poor infrastructural support from institutions,
      excessive workloads and inadequate supervision were factors preventing optimal
      training of paediatric interns. CONCLUSIONS: The SA version of the PHEEM tool
      used was found to be a reliable and valid instrument for use in interns amongst
      high disease burdened contexts. Various obstacles to creating an ideal learning
      environment for paediatric interns were identified to be in need of urgent
      review. Key differences in perceptions of an ideal learning environment between
      interns and their supervisors need to be fully explored as these may result in
      sub-optimal supervision and mentoring.

PMID- 29187180
TI  - Use of autogenous onlay bone graft for uncontained tibial bone defects in primary
      total knee arthroplasty.
AB  - BACKGROUND: The use of autogenous bone graft is a well-known technique for
      reconstruction of tibial bone defects in primary total knee arthroplasty (TKA).
      In cases where the size of the bone graft is inappropriate, the stability of bone
      graft fixation and subsequent bone graft to host bone incorporation may be
      compromised. We describe a simple and reliable technique of reconstruction in a
      proximal tibia bone defect at the time of primary TKA by using autogenous onlay
      bone graft (AOBG). METHODS: Records were reviewed of 19 patients (mean age, 72
      years) who underwent primary TKA using AOBG without the additional allogenous
      bone or metal augments, between August 2013 and August 2014. RESULTS: Mean Knee
      Society score (KSS) in the 22 knees was significantly higher postoperatively than
      preoperatively (92 +/- 4 vs. 30 +/- 7, P < 0.001). The mean range of motion (ROM)
      in the 22 knees, which was 106 +/- 12 degrees  preoperatively, improved to 112 +/
      10 degrees  at last follow-up, but this difference was not significant (P =
      0.32). No migration of implants and presence of radiolucent lines at the bone
      cement-prosthesis interface were observed. Furthermore, the serial radiographs of
      19 patients had a mean time of 3.2 months (range, 2.7-4.4 months) for solid union
      with cross trabeculation between the proximal tibial bone and graft. CONCLUSIONS:
      This simple AOBG supplement technique may biologically promote graft to host bone
      healing by enhancing fixation stability without the additional fixatives and
      assist the surgeon in managing the varying nature of uncontained bone defects.
      TRIAL REGISTRATION: Trial registration number: KCT0002328 , May 15, 2017.

PMID- 29187181
TI  - Could cone-beam computed tomography demonstrate the lateral accessory canals?
AB  - BACKGROUND: Recently, using cone-beam computed tomography (CBCT) to assess root
      canal morphology has become popular; however, few studies have examined its
      efficiency to assess the entire root canals, including the tiny lateral and
      accessory canals (LACs). This study aimed to assess the ability of CBCT to
      evaluate the root canal of mandibular incisors at three different scanning
      settings, compared with the canal staining and tooth clearing (CS) technique as
      the gold standard. METHODS: CBCT images of 70 extracted mandibular incisors were
      taken using NewTom VG CBCT at high-resolution scan mode (HZ), zoom scan mode
      (ZS), and full scan mode (FS), with different scanning settings. A radiologist, a
      postgraduate student, and an endodontist assessed the root canal morphology in a
      blinded manner. The number of root canals (NC), canal configuration according to
      Vertucci's classification (VC), and LACs were evaluated twice by each evaluator
      using the CBCT images, in comparison with CS. Comparisons of the differences were
      used the chi-square test, and the intra-evaluator and inter-evaluator agreement
      were used the Kappa statistics; the significance level was set at 0.05. RESULTS:
      The voxel dimension of HZ, ZS and FS modes were 0.125 mm, 0.20 mm and 0.25 mm
      respectively, and the HZ mode had significant increased scanning doses. For NC,
      the diagnostic accuracy was >90% in all three modes, with no significant
      difference among the evaluators and modes. VC and LAC could only be evaluated in
      HZ mode. For VC, the accuracies were 97.1%, 94.3%, and 92.9% respectively, with
      no significant differences among the three evaluators. For LAC, the accuracies
      were 80.0%, 13.3%, and 33.3% respectively, and there were significant differences
      among the three evaluators. Intra-evaluator agreement was excellent, with the
      kappa values indicating "perfect" to "substantial" agreement. Inter-evaluator
      agreement was excellent for NC and VC; however, Kappa values could not be
      analyzed due to LACs detected were so variable. CONCLUSIONS: As far as possible,
      the HZ mode should be chosen to demonstrate the root canal system, and partial
      LACs could be detected using this mode; however, the potential benefit of the
      diagnostic information must be weighed against the increased radiation dose.

PMID- 29187182
TI  - Sacroiliac joint tuberculosis: surgical management by posterior open-window focal
      debridement and joint fusion.
AB  - BACKGROUND: Sacroiliac joint tuberculosis(SJT) is relatively uncommon, but it may
      cause severe sacroiliac joint destruction and functional disorder. Few studies in
      the literature have been presented on SJT, reports of surgical treatment for SJT
      are even fewer. In this study, we retrospectively reviewed surgical management of
      patients with severe SJT of 3 different types and proposed to reveal the clinical
      manifestations and features and aim to determine the efficiency and security of
      such surgical treatment. METHODS: We reviewed 17 patients with severe SJT of 3
      different types who underwent posterior open-window focal debridement and bone
      graft for joint fusion. Among them,five patients with anterior sacral abscess had
      anterior abscess curettage before debridement. Two patients with lumbar vertebral
      tuberculosis received one-stage posterior tuberculous debridement, interbody
      fusion and instrumentation. Follow-up was performed 36 months (26 to 45 months)
      using the following parameters: erythrocyte sedimentation rate(ESR), status of
      joint bony fusion on CT scan, visual analogue scale (VAS) and the Oswestry
      Disability Index (ODI). RESULTS: Buttock pain and low back pain were
      progressively relieved with time. 6 months later, pain was not obvious, and ESR
      resumed to normal levels within 3 months. Solid fusion of the sacroiliac joint
      occurred within 12 months in all cases. No complications or recurrence occurred.
      At final follow-up, all patients had no pain or only minimal discomfort over the
      affected joint and almost complete functional recovery. CONCLUSIONS: Posterior
      open-window focal debridement and joint fusion is an efficient and secure
      surgical method to treat severe SJT. If there is an abscess in the front of the
      sacroiliac joint, anterior abscess curettage should be performed as a supplement.

PMID- 29187183
TI  - Low bone turnover in premenopausal women with type 2 diabetes mellitus as an
      early process of diabetes-associated bone alterations: a cross-sectional study.
AB  - BACKGROUND: Individuals with Diabetes Mellitus (DM) are at increased risk for
      fracture due to the decrease in bone strength and quality. Serum procollagen type
      I intact N-terminal (P1NP) and serum C-terminal cross-linking telopeptide of type
      I collagen (CTX) as markers of bone formation and resorption, respectively, have
      been reported to be decreased in T2DM. It remains unclear whether diabetes
      associated alterations in the bone turnover of T2DM individuals are related to
      the longer duration of the disease or may occur earlier. Furthermore, previous
      studies on BTMs in T2DM individuals have mostly been done in postmenopausal women
      with T2DM, which might have masked the DM-induced alterations of bone turnover
      with concurrent estrogen deficiency. This study aims to assess the levels of
      serum P1NP and CTX as markers of bone turnover in premenopausal women with and
      without T2DM. METHODS: This cross-sectional study involves 41 premenopausal women
      with T2DM, and 40 premenopausal women without DM. Sampling was done
      consecutively. P1NP and CTX measurement was done using the electrochemi
      luminescence immunoassay (ECLIA) method. Other data collected include levels of
      HbA1C, ALT, creatinine, eGFR and lipid profile. RESULTS: Median (interquartile
      range) P1NP in T2DM is 29.9 ng/ml (24.7-41.8 ng/ml), while in non-DM is 37.3
      ng/ml, (30.8-47.3 ng/ml; p = 0.007). Median (interquartile range) CTX in T2DM is
      0.161 ng/ml (0.106-0.227 ng/ml), while in non-DM is 0.202 ng/ml (0.166-0.271
      ng/ml; p = 0.0035). Levels of P1NP and CTX in the T2DM group did not correlate
      with the duration of disease, age, BMI or the levels of HbA1C. CONCLUSIONS:
      Premenopausal women with T2DM indeed have lower bone turnover when compared with
      non-DM controls. This significantly lower bone turnover process starts relatively
      early in the premenopausal age, independent of the duration of DM. Gaining
      understanding of the early pathophysiology of altered bone turnover may be key in
      developing preventive strategies for diabetoporosis.

PMID- 29187185
TI  - In-hospital prescription changes and documentation in the medical records of the
      primary care provider: results from a medical record review study.
AB  - BACKGROUND: An increasing number of transitions due to substitution of care of
      more complex patients urges insight in and improvement of transitional medication
      safety. While lack of documentation of prescription  changes and/or lack of
      information exchange between settings likely cause adverse drug events, frequency
      of  occurrence of these causes is not clear. Therefore, we aimed at determining
      the frequency of in-hospital patients' prescription  changes that are not or
      incorrectly documented in their primary care provider's (PCP) medical record.
      METHODS: A medical record review study was performed in a database linking
      patients' medical records of hospital and PCP. A random sample (n = 600) was
      drawn from all 1399 patients who were registered at a participating primary care
      practice as well as the gastroenterology or cardiology department in 2013 of the
      University  Medical Center Utrecht, the Netherlands. Outcomes were the number of
      in-hospital prescription changes that was not  or incorrectly documented in the
      medical record of the PCP, and timeliness of documentation. RESULTS: Records of
      390 patients included one or more primary-secondary care transitions; in total we
      identified 1511 transitions. During these transitions, 408 in-hospital
      prescription changes were made, of which 31% was  not or incorrectly documented
      in the medical record of the PCP within the next 3 months. In case changes were
      documented, the median number of days between hospital visit and documentation
      was 3 (IQR 0-18). CONCLUSIONS: One third of in-hospital prescription changes was
      not or incorrectly documented in the PCP's record, which likely puts patients at
      risk of adverse drug events after hospital visits. Such flawed reliability of a
      routine  care process is unacceptable and warrants improvement and close
      monitoring.

PMID- 29187186
TI  - A mobile and web-based clinical decision support and monitoring system for
      diabetes mellitus patients in primary care: a study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Physicians' guideline use rates for diagnosis, treatment and
      monitoring of diabetes mellitus (DM) is very low. Time constraints, patient
      overpopulation, and complex guidelines require alternative solutions for real
      time patient monitoring. Rapidly evolving e-health technology combined with
      clinical decision support and monitoring systems (CDSMS) provides an effective
      solution to these problems. The purpose of the study is to develop a user
      friendly, comprehensive, fully integrated web and mobile-based Clinical Decision
      Support and Monitoring System (CDSMS) for the screening, diagnosis, treatment,
      and monitoring of DM diseases which is used by physicians and patients in primary
      care and to determine the effectiveness of the system. METHODS: The CDSMS will be
      based on evidence-based guidelines for DM disease. A web and mobile-based
      application will be developed in which the physician will remotely monitor
      patient data through mobile applications in real time. The developed CDSMS will
      be tested in two stages. In the first stage, the usability, understandability,
      and adequacy of the application will be determined. Five primary care physicians
      will use the developed application for at least 16 DM patients. Necessary
      improvements will be made according to physician feedback. In the second phase, a
      parallel, single-blind, randomized controlled trial will be implemented. DM
      diagnosed patients will be recruited for the CDSMS trial by their primary care
      physicians. Ten physicians and their 439 patients will be involved in the study.
      Eligible participants will be assigned to intervention and control groups with
      simple randomization. The significance level will be accepted as p < 0.05. In the
      intervention group, the system will make recommendations on patient monitoring,
      diagnosis, and treatment. These recommendations will be implemented at the
      physician's discretion. Patients in the control group will be treated by
      physicians according to current DM treatment standards. Patients in both groups
      will be monitored for 6 months. Patient data will be compared between 0th and 6th
      month of the study. . Clinical and laboratory outcomes will be assessed in person
      while others will be self-assessed online. DISCUSSION: The developed system will
      be the first of its kind to utilize evidence based guidelines to provide health
      services to DM patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02917226 . 28
      September 2016.

PMID- 29187184
TI  - Rheumatic heart disease: infectious disease origin, chronic care approach.
AB  - BACKGROUND: Rheumatic heart disease (RHD) is a chronic cardiac condition with an
      infectious aetiology, causing high disease burden in low-income settings.
      Affected individuals are young and associated morbidity is high. However, RHD is
      relatively neglected due to the populations involved and its lower incidence
      relative to other heart diseases. METHODS AND RESULTS: In this narrative review,
      we describe how RHD care can be informed by and integrated with models of care
      developed for priority non-communicable diseases (coronary heart disease), and
      high-burden communicable diseases (tuberculosis). Examining the four-level
      prevention model (primordial through tertiary prevention) suggests primordial and
      primary prevention of RHD can leverage off existing tuberculosis control efforts,
      given shared risk factors. Successes in coronary heart disease control provide
      inspiration for similarly bold initiatives for RHD. Further, we illustrate how
      the Chronic Care Model (CCM), developed for use in non-communicable diseases,
      offers a relevant framework to approach RHD care. Systems strengthening through
      greater integration of services can improve RHD programs. CONCLUSION:
      Strengthening of systems through integration/linkages with other well-performing
      and resourced services in conjunction with policies to adopt the CCM framework
      for the secondary and tertiary prevention of RHD in settings with limited
      resources, has the potential to significantly reduce the burden of RHD globally.
      More research is required to provide evidence-based recommendations for policy
      and service design.

PMID- 29187187
TI  - Syndromic surveillance for West Nile virus using raptors in rehabilitation.
AB  - BACKGROUND: Wildlife rehabilitation centers routinely gather health-related data
      from diverse species. Their capability to signal the occurrence of emerging
      pathogens and improve traditional surveillance remains largely unexplored. This
      paper assessed the utility for syndromic surveillance of raptors admitted to The
      Raptor Center (TRC) to signal circulation of West Nile Virus (WNV) in Minnesota
      between 1990 and 2014. An exhaustive descriptive analysis using grouping time
      series structures and models of interrupted times series was conducted for
      indicator subsets. RESULTS: A total of 13,080 raptors were monitored. The most
      representative species were red-tailed hawks, great horned owls, Cooper's hawks,
      American kestrels and bald eagles. Results indicated that temporal patterns of
      accessions at the TRC changed distinctively after the incursion of WNV in 2002.
      The frequency of hawks showing WNV-like signs increased almost 3 times during
      July and August, suggesting that monitoring of hawks admitted to TRC with WNV
      like signs could serve as an indicator of WNV circulation. These findings were
      also supported by the results of laboratory diagnosis. CONCLUSIONS: This study
      demonstrates that monitoring of data routinely collected by wildlife
      rehabilitation centers has the potential to signal the spread of pathogens that
      may affect wild, domestic animals and humans, thus supporting the early detection
      of disease incursions in a region and monitoring of disease trends. Ultimately,
      data collected in rehabilitation centers may provide insights to efficiently
      allocate financial and human resources on disease prevention and surveillance.

PMID- 29187188
TI  - Massive pelvic recurrence of uterine leiomyomatosis with intracaval-intracardiac
      extension: video case report and literature review.
AB  - BACKGROUND: Uterine leiomyomas represent the gynecological neoplasm with the
      highest prevalence worldwide. This apparently benign pathological entity may
      permeate into the venous system causing the so-called intravenous leiomyomatosis
      of the uterus (IVL). IVL may seldom extend to large caliber veins and reach the
      right cardiac chambers or pulmonary arteries and cause signs of right sided
      congestive heart failure and sudden death. Due to its low incidence, however, IVL
      with intracardiac extension is often misdiagnosed resulting in deferred
      treatment. No consensus has been obtained regarding the standard surgical
      approach to be used for this rare condition. We describe the case of a massive
      pelvic recurrence of uterine leiomyomatosis with intracardiac extension and
      provide a review of the literature, analyzing management and surgical outcomes.
      CASE PRESENTATION: We present the case of a 46-year-old premenopausal woman
      presenting with lower-extremity edema, recurrent syncopes and a history of
      subtotal hysterectomy for multiple uterine fibroids. She was diagnosed with
      pelvic recurrence of uterine leiomyomatosis and IVL with cardiac involvement. A
      two-stage surgical excision of the intracardiac-intracaval mass and pelvic
      leiomyomatosis was performed. The patient had an uneventful recovery and no
      evidence of recurrence was observed on follow-up. CONCLUSIONS: By virtue of the
      rarity of the present pathology, awareness is widely scarce and diagnosis is
      often delayed. Early recognition is difficult due to initial aspecific and subtle
      clinical manifestations. Nevertheless, suspicion should be held high in
      premenopausal women with known history of uterine leiomyomata, presenting with
      cardiovascular symptoms and evidence of a free-floating mass within the right
      cardiac chambers. In-depth imaging is crucial for defining its anatomical origin
      and relations. Prompt surgical treatment with radical excision of pelvic and
      intravenous leiomyomatosis guarantees favorable outcomes and excellent prognosis
      with low rates of recurrence, whereas delayed diagnosis and treatment exposes to
      increased risk of congestive heart failure and sudden death.

PMID- 29187189
TI  - Operational integration in primary health care: patient encounters and workflows.
AB  - BACKGROUND: Despite several countrywide attempts to strengthen and standardise
      the primary healthcare (PHC) system, Greece is still lacking a sustainable,
      policy-based model of integrated services. The aim of our study was to identify
      operational integration levels through existing patient care pathways and to
      recommend an alternative PHC model for optimum integration. METHODS: The study
      was part of a large state-funded project, which included 22 randomly selected PHC
      units located across two health regions of Greece. Dimensions of operational
      integration in PHC were selected based on the work of Kringos and colleagues. A
      five-point Likert-type scale, coupled with an algorithm, was used to capture and
      transform theoretical framework features into measurable attributes. PHC services
      were grouped under the main categories of chronic care, urgent/acute care,
      preventive care, and home care. A web-based platform was used to assess patient
      pathways, evaluate integration levels and propose improvement actions. Analysis
      relied on a comparison of actual pathways versus optimal, the latter ones having
      been identified through literature review. RESULTS: Overall integration varied
      among units. The majority (57%) of units corresponded to a basic level.
      Integration by type of PHC service ranged as follows: basic (86%) or poor (14%)
      for chronic care units, poor (78%) or basic (22%) for urgent/acute care units,
      basic (50%) for preventive care units, and partial or basic (50%) for home care
      units. The actual pathways across all four categories of PHC services differed
      from those captured in the optimum integration model. Certain similarities were
      observed in the operational flows between chronic care management and
      urgent/acute care management. Such similarities were present at the highest level
      of abstraction, but also in common steps along the operational flows.
      CONCLUSIONS: Existing patient care pathways were mapped and analysed, and
      recommendations for an optimum integration PHC model were made. The developed web
      platform, based on a strong theoretical framework, can serve as a robust
      integration evaluation tool. This could be a first step towards restructuring and
      improving PHC services within a financially restrained environment.

PMID- 29187191
TI  - Fostering development of nursing practices to support integrated care when
      implementing integrated care pathways: what levers to use?
AB  - BACKGROUND: Care integration has been the focus of recent health system reforms.
      Given their functions at all levels of the care continuum, nurses have a
      substantial and primordial role to play in such integration processes. The aim of
      this study was to identify levers and strategies that organizations can use to
      support the development of a nursing practice aligned with the requirements of
      care integration in a health and social services centre (HSSC) in Quebec.
      METHODS: The research design was a cross-sectional descriptive qualitative study
      based on a single case study with nested levels of analysis. The case was a
      public, multi-disciplinary HSSC in a semi-urban region of Quebec. Semi-structured
      interviews with 37 persons (nurses, professionals, managers, administrators)
      allowed for data saturation and ensured theoretical representation by covering
      four care pathways constituting different care integration contexts. Analysis
      involved four steps: preparing a predetermined list of codes based on the
      reference framework developed by Minkman (2011); coding transcript content;
      developing general and summary matrices to group observations for each care
      pathway; and creating a general model showing the overall results for the four
      pathways. RESULTS: The organization's capacity for response with regard to
      developing an integrated system of services resulted in two types of
      complementary interventions. The first involved investing in key resources and
      renewing organizational structures; the second involved deploying a series of
      organizational and clinical-administrative processes. In resource terms,
      integration efforts resulted in setting up new strategic services, re-arranging
      physical infrastructures, and deploying new technological resources.
      Organizational and clinical-administrative processes to promote integration
      involved renewing governance, improving the flow of care pathways, fostering
      continuous quality improvement, developing new roles, promoting clinician
      collaboration, and strengthening care providers' capacities. However, progress in
      these areas was offset by persistent constraints. CONCLUSIONS: The results
      highlight key levers organizations can use to foster the implementation and
      institutionalization of integrative nursing practices. They show that progress in
      this area requires a combination of strategies using multiple complementary
      levers. They also suggest that such progress calls for rethinking not only the
      deployment of certain organizational resources and structures, but also a series
      of organizational and clinical processes.

PMID- 29187190
TI  - Ethical considerations in forensic genetics research on tissue samples collected
      post-mortem in Cape Town, South Africa.
AB  - BACKGROUND: The use of tissue collected at a forensic post-mortem for forensic
      genetics research purposes remains of ethical concern as the process involves
      obtaining informed consent from grieving family members. Two forensic genetics
      research studies using tissue collected from a forensic post-mortem were recently
      initiated at our institution and were the first of their kind to be conducted in
      Cape Town, South Africa. MAIN BODY: This article discusses some of the ethical
      challenges that were encountered in these research projects. Among these
      challenges was the adaptation of research workflows to fit in with an
      exceptionally busy service delivery that is operating with limited resources.
      Whilst seeking guidance from the literature regarding research on deceased
      populations, it was noted that next of kin of decedents are not formally
      recognised as a vulnerable group in the existing ethical and legal frameworks in
      South Africa. The authors recommend that research in the forensic mortuary
      setting is approached using guidance for vulnerable groups, and the benefit to
      risk standard needs to be strongly justified. Lastly, when planning forensic
      genetics research, consideration must be given to the potential of uncovering
      incidental findings, funding to validate these findings and the feedback of
      results to family members; the latter of which is recommended to occur through a
      genetic counsellor. CONCLUSION: It is hoped that these experiences will
      contribute towards a formal framework for conducting forensic genetic research in
      medico-legal mortuaries in South Africa.

PMID- 29187192
TI  - Comprehensive metabolic profiling of chronic low-grade inflammation among
      generally healthy individuals.
AB  - BACKGROUND: Inflammation occurs as an immediate protective response of the immune
      system to a harmful stimulus, whether locally confined or systemic. In contrast,
      a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well
      known risk factor in the development of common diseases like diabetes or
      atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C
      reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used
      to reveal inflammatory processes. In order to gain a deeper insight regarding
      inflammation-related changes in metabolism, the present study assessed the
      metabolic patterns associated with alterations in inflammatory markers. METHODS:
      Based on mass spectrometry and nuclear magnetic resonance spectroscopy we
      determined a comprehensive panel of 613 plasma and 587 urine metabolites among
      925 apparently healthy individuals. Associations between inflammatory markers,
      namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear
      regression analyses controlling for common confounders. Additionally, we tested
      for a discriminative signature of an advanced inflammatory state using random
      forest analysis. RESULTS: HsCRP, WBC, and fibrinogen were significantly
      associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites,
      respectively. Identified metabolites were related to the bradykinin system,
      involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the
      urea cycle (e.g., ornithine or citrulline). In particular, urine 3'-sialyllactose
      was found as a novel metabolite related to inflammation. Prediction of an
      advanced inflammatory state based solely on 10 metabolites was well feasible
      (median AUC: 0.83). CONCLUSIONS: Comprehensive metabolic profiling confirmed the
      far-reaching impact of inflammatory processes on human metabolism. The identified
      metabolites included not only those already described as immune-modulatory but
      also completely novel patterns. Moreover, the observed alterations provide
      molecular links to inflammation-associated diseases like diabetes or
      cardiovascular disorders.

PMID- 29187193
TI  - Paediatric case mix in a rural clinical school is relevant to future practice.
AB  - BACKGROUND: Exposure to a representative case mix is essential for clinical
      learning, with logbooks established as a way of demonstrating patient contacts.
      Few studies have reported the paediatric case mix available to geographically
      distributed students within the same medical school. Given international interest
      in expanding medical teaching locations to rural contexts, equitable case
      exposure in rural relative to urban settings is topical. The Rural Clinical
      School of Western Australia locates students up to 3500 km from the urban
      university for an academic year. There is particular need to examine paediatric
      case mix as a study reported Australian graduates felt unprepared for paediatric
      rotations. We asked: Does a rural clinical school provide a paediatric case mix
      relevant to future practice? How does the paediatric case mix as logged by rural
      students compare with that by urban students? METHODS: The 3745 logs of 76 urban
      and 76 rural consenting medical students were categorised by presenting symptoms
      and compared to the Australian Institute of Health and Welfare (AIHW) database
      Major Diagnostic Categories (MDCs). RESULTS: Rural and urban students logged core
      paediatric cases, in similar order, despite the striking difference in geographic
      locations. The pattern of overall presenting problems closely corresponded to
      Australian paediatric hospital admissions. Rural students logged 91% of cases in
      secondary healthcare settings; urban students logged 90% of cases in tertiary
      settings. The top four presenting problems were ENT/respiratory,
      gastrointestinal/urogenital, neurodevelopmental and musculoskeletal; these made
      up 60% of all cases. Rural and urban students logged similar proportions of
      infants, children and adolescents, with a variety of case morbidity. CONCLUSIONS:
      Rural clinical school students logged a mix of core paediatric cases relevant to
      illnesses of Australian children admitted to public hospitals, with similar order
      and pattern by age group to urban students, despite major differences in clinical
      settings. Logged cases met the curriculum learning outcomes of graduates. Minor
      variations were readily addressed via recommendations about logging. This paper
      provides evidence of the legitimacy of student logs as useful tools in affirming
      appropriate paediatric case mix. It validates the rural clinical school context
      as appropriate for medical students to prepare for future clinical paediatric
      practice.

PMID- 29187194
TI  - Treatment effects of renin-angiotensin aldosterone system blockade on kidney
      failure and mortality in chronic kidney disease patients.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a leading cause of death before and
      after onset of end-stage renal disease (ESRD). Knowing treatments that can delay
      disease progression will lead to reduced mortality. We therefore aimed to
      estimate the effectiveness of renin angiotensin aldosterone system (RAAS)
      blockade on CKD progression. METHODS: We conducted a retrospective CKD cohort at
      Ubon Ratchathani province, Thailand from 1997 to 2011. ESRD was defined as
      estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2, dialysis, or
      kidney transplantation. All-cause mortality was verified until December 31, 2011.
      A counterfactual-framework was applied to estimate the effectiveness of RAAS
      blockade on outcomes, i.e., ESRD, death before and after ESRD. RAAS blockade was
      categorized according to duration of use <0.25 year, 0.25-1 year (RAAS1), and >1
      year (RAAS2). An augmented inverse-probability weighting (AIPW) method was used
      to estimate potential-outcome mean (POM) and average treatment-effect (ATE).
      Multi-logit and Poisson regressions were used for treatment and outcome models,
      respectively. Analyses were stratified by ESRD, death before/after ESRD for
      diabetic and non-diabetic groups. STATA 14.0 was used for statistical analyses.
      RESULTS: Among 15,032 diabetic patients, 2346 (15.6%), 2351 (18.5%), and 1607
      (68.5%) developed ESRD, died before ESRD, and died after ESRD, respectively. Only
      RAAS2 effect was significant on ESRD, death before and after ESRD. The ESRD rates
      were 12.9%, versus 20.0% for RAAS2 and non-RAAS, respectively, resulted in
      significant risk differences (RD) of -7.2% (95% CI: -8.8%, -5.5%), and a numbers
      needed-to-treat (NNT) of 14. Death rates before ESRD for these corresponding
      groups were 14.4% (12.9%, 15.9%) and 19.6% (18.7%, 20.4%) with a NNT of 19. Death
      rates after ESRD in RAAS2 was lower than non-RASS group (i.e., 62.8% (55.5%,
      68.9%) versus 68.1% (65.9%, 70.4%)) but this was not significant. RAAS2 effects
      on ESRD and death before ESRD were persistently significant in non-diabetic
      patients (n = 17,074) but not for death after ESRD with the NNT of about 15 and
      16 respectively. CONCLUSIONS: Receiving RAAS blockade for 1 year or longer could
      prevent both CKD progression to ESRD and premature mortality.

PMID- 29187195
TI  - Prevalence, antimicrobial susceptibility and risk factors associated with non
      typhoidal Salmonella on Ugandan layer hen farms.
AB  - BACKGROUND: Non-typhoidal Salmonella (NTS) are among the leading global foodborne
      pathogens and a significant public health threat. Their occurrence in animal
      reservoirs and their susceptibilities to commonly used antimicrobials are poorly
      understood in developing countries. The aim of this study was to estimate the
      prevalence, determine antimicrobial susceptibility and identify risk factors
      associated with NTS presence in laying hen farms in Uganda through a cross
      sectional study. RESULTS: Pooled faecal samples were collected from 237 laying
      hen farms and these were analysed for NTS following standard laboratory
      procedures. In total, 49 farms (20.7%; 95% Confidence interval (CI): 15.6-25.6%)
      were positive for NTS presence. Altogether, ten Salmonella serotypes were
      identified among the confirmed 78 isolates, and the predominant serotypes were
      Salmonella Newport (30.8%), S. Hadar (14.1%), S. Aberdeen (12.8%), S. Heidelberg
      (12.8%), and S. Bolton (12.8%). Phenotypic antimicrobial resistance was detected
      in 45(57.7%) of the isolates and the highest resistance was against ciprofloxacin
      (50.0%) followed by sulphonamides (26.9%) and sulphamethoxazole/trimethoprim
      (7.7%). Resistance was significantly associated with sampled districts (p =
      0.034). Resistance to three or more drugs, multi-drug resistance (MDR) was
      detected in 12 (15.4%) of the isolates, 9 (75%) of these were from Wakiso
      district. A multivariable logistic model identified large farm size (OR = 7.0;
      95% CI: 2.5-19.8) and the presence of other animal species on the farm (OR = 5.9;
      95% CI: 2.1-16.1) as risk factors for NTS prevalence on farms. Having a separate
      house for birds newly brought to the farms was found to be protective (OR = 0,4;
      95% CI: 0.2-0.8). CONCLUSION: This study has highlighted a high prevalence and
      diversity of NTS species in laying hen farms in Uganda and identified associated
      risk factors. In addition, it has demonstrated high levels of antimicrobial
      resistance in isolates of NTS. This could be because of overuse or misuse of
      antimicrobials in poultry production. Also importantly, the insights provided in
      this study justifies a strong case for strengthening One Health practices and
      this will contribute to the development of NTS control strategies at local,
      national and international levels.

PMID- 29187196
TI  - Development of a monitoring instrument to assess the performance of the Swiss
      primary care system.
AB  - BACKGROUND: The Swiss health system is customer-driven with fee-for-service
      paiement scheme and universal coverage. It is highly performing but expensive and
      health information systems are scarcely implemented. The Swiss Primary Care
      Active Monitoring (SPAM) program aims to develop an instrument able to describe
      the performance and effectiveness of the Swiss PC system. METHODS: Based on a
      Literature review we developed a conceptual framework and selected indicators
      according to their ability to reflect the Swiss PC system. A two round modified
      RAND method with 24 inter-/national experts took place to select
      primary/secondary indicators (validity, clarity, agreement). A limited set of
      priority indicators was selected (importance, priority) in a third round.
      RESULTS: A conceptual framework covering three domains (structure, process,
      outcome) subdivided into twelve sections (funding, access, organisation/ workflow
      of resources, (Para-)Medical training, management of knowledge, clinical
      /interpersonal care, health status, satisfaction of PC providers/ consumers,
      equity) was generated. 365 indicators were pre-selected and 335 were finally
      retained. 56 were kept as priority indicators.- Among the remaining, 199 were
      identified as primary and 80 as secondary indicators. All domains and sections
      are represented. CONCLUSION: The development of the SPAM program allowed the
      construction of a consensual instrument in a traditionally unregulated health
      system through a modified RAND method. The selected 56 priority indicators render
      the SPAM instrument a comprehensive tool supporting a better understanding of the
      Swiss PC system's performance and effectiveness as well as in identifying
      potential ways to improve quality of care. Further challenges will be to update
      indicators regularly and to assess validity and sensitivity-to-change over time.

PMID- 29187197
TI  - Changes in clavicle length in acute fractures within 3 weeks: a prospective
      ultrasonographic study of 59 patients.
AB  - BACKGROUND: Within traumatology a common indication for acute surgery of
      fractured clavicles is bone shortening over 2 cm. This indication is among but a
      few indications; which are recommended to be treated operatively within the very
      first weeks after a fracture. Theoretically clavicle fractures could become less
      shortened over time due to decreasing muscle pull. If this reduced shortening
      does indeed happen, some patients with initial bone shortening over 2 cm could
      perhaps be treated conservatively? However, it is unknown what happens to the
      length of the clavicle within the first weeks after a fracture. The aim of this
      study was to investigate if the length of the fresh fractured clavicles changes
      within the first three weeks. METHODS: Rested length measurements using
      navigation ultrasound were done on 59 patients with a fractured clavicle.
      Measurements were performed within the first three weeks after a lateral or mid
      clavicular fracture. The inclusion period was from March 2014 to February 2016.
      Median age was 40 years and age range was 18-81 years. The data was analyzed
      using mixed linear models. RESULTS: The clavicle length showed no change within
      the first three weeks after fracture (p = 0.24). CONCLUSION: Fractured clavicles
      retain their length for the first three weeks.

PMID- 29187198
TI  - Preliminary reference intervals and the impact of citrate storage time for
      thrombelastography in cats including delta and the velocity curve.
AB  - BACKGROUND: Thrombelastography is a useful tool in assessment of hemostasis.
      Beside the traditional variables, the velocity curve and the variable delta have
      lately earned attention. The velocity curve provides knowledge about the speed of
      clot formation including information about thrombin generation. Delta, which only
      reflects enzymatic coagulation, allows the determination of the origin of
      hypercoagulability when compared to clot rigidity, a variable that reflects both
      platelet and enzymatic activity. The aim was to establish preliminary reference
      intervals for feline thrombelastography including the velocity curve variables
      and delta obtained after 60 min of storage including the assessment of
      coefficients of variation. Furthermore, the effect of citrate storage time (30
      versus 60 min) on feline thrombelastography will be determined. RESULTS:
      Prolonged storage times significantly reduced reaction (R) (P = 0.019) and
      clotting (K) (P = 0.008) times, split point (SP) (P = 0.019) and time to maximum
      rate of thrombus generation (TMRTG) (P = 0.023) values whereas maximum rate of
      thrombus generation (MRTG) significantly increased (P = 0.040). Preliminary
      reference intervals: R (min): 2.7-18.1; K (min): 0.8-3.9; alpha ( degrees ): 27.6
      75.2; maximum amplitude (mm): 18.5-62.5; clot rigidity (dyn/cm2): 1.2-8.2;
      coagulation index: -4.6 - 2.6; SP (min): 2.4-15.4; delta (min): 0.3-3.1; thrombus
      generation (mm/min): 255.3-751.2; MRTG (mm/min): 4.0-19.3; TMRTG (min): 3.5-22.0;
      maximum rate of lysis (mm/min): 0.0-4.7 and time to maximum rate of lysis (min):
      0.4-55.8. CONCLUSION: Storage for 60 versus 30 min induces hypercoagulable
      tracings including the velocity curve, some of which variables (MRTG, TMRTG)
      might function as sensitive markers for changes in the coagulation activity.
      Because of the impact of citrate storage time on thrombelastography, reference
      intervals have to be established using a specific and constant storage time in
      each laboratory.

PMID- 29187199
TI  - Novel ELISA method as exploratory tool to assess immunity induced by radiated
      attenuated sporozoites to decipher protective immunity.
AB  - BACKGROUND: Whole parasite vaccines provide a unique opportunity for dissecting
      immune mechanisms and identify antigens that are targeted by immune responses
      which have the potential to mediate sterile protection against malaria
      infections. The radiation attenuated sporozoite (PfSPZ) vaccine has been
      considered the gold standard for malaria vaccines because of its unparalleled
      efficacy. The immunogenicity of this and other vaccines continues to be evaluated
      by using recombinant proteins or peptides of known sporozoite antigens. This
      approach, however, has significant limitations by relying solely on a limited
      number of known pathogen-associated immune epitopes. Using the full range of
      antigens expressed by the sporozoite will enable the comprehensive immune
      profiling of humoral immune responses induced by whole parasite vaccines. To
      address this challenge, a novel ELISA based on sporozoites was developed.
      RESULTS: The SPZ-ELISA method described in this report can be performed with
      either freshly dissected sporozoites or with cryopreserved sporozoite lysates.
      The use of a fixative for reproducible coating is not required. The SPZ-ELISA was
      first validated using monoclonal antibodies specific for CSP and TRAP and then
      used for the characterization of immune sera from radiation attenuated sporozoite
      vaccinees. CONCLUSION: Applying this simple and highly reproducible approach to
      assess immune responses induced by malaria vaccines, both recombinant and whole
      parasite vaccines, (1) will help in the evaluation of immune responses induced by
      antigenically complex malaria vaccines such as the irradiated SPZ-vaccine, (2)
      will facilitate and accelerate the identification of immune correlates of
      protection, and (3) can also be a valuable assessment tool for antigen discovery
      as well as down-selection of vaccine formulations and, thereby, guide vaccine
      design.

PMID- 29187200
TI  - ApoA-I/A-II-HDL positively associates with apoB-lipoproteins as a potential
      atherogenic indicator.
AB  - BACKGROUND: We recently reported distinct nature of high-density lipoproteins
      (HDL) subgroup particles with apolipoprotein (apo) A-I but not apoA-II (LpAI) and
      HDL having both (LpAI:AII) based on the data from 314 Japanese. While plasma HDL
      level almost exclusively depends on concentration of LpAI having 3 to 4 apoA-I
      molecules, LpAI:AII appeared with almost constant concentration regardless of
      plasma HDL levels having stable structure with two apoA-I and one disulfide
      dimeric apoA-II molecules (Sci. Rep. 6; 31,532, 2016). The aim of this study is
      further characterization of LpAI:AII with respect to its role in atherogenesis.
      METHODS: Association of LpAI, LpAI:AII and other HDL parameters with apoB
      lipoprotein parameters was analyzed among the cohort data above. RESULTS: ApoA-I
      in LpAI negatively correlated with the apoB-lipoprotein parameters such as apoB,
      triglyceride, nonHDL-cholesterol, and nonHDL-cholesterol + triglyceride, which
      are apparently reflected in the relations of the total HDL parameters to apoB
      lipoproteins. In contrast, apoA-I in LpAI:AII and apoA-II positively correlated
      to the apoB-lipoprotein parameters even within their small range of variation.
      These relationships are independent of sex, but may slightly be influenced by the
      activity-related CETP mutations. CONCLUSIONS: The study suggested that LpAI:AII
      is an atherogenic indicator rather than antiatherogenic. These sub-fractions of
      HDL are to be evaluated separately for estimating atherogenic risk of the
      patients.

PMID- 29187201
TI  - Sirt1 interaction with active Smad2 modulates transforming growth factor-beta
      regulated transcription.
AB  - BACKGROUND: The simplicity of Transforming Growth Factor beta (TGFbeta) signaling
      pathway, linear and non-amplified, hardly sustains its variety of responses. This
      is often justified by the complex regulation showed by Smad proteins, TGFbeta
      signaling intracellular transducers, object of post-translational modifications
      that modulate TGFbeta-dependent transcription. Protein acetylation is emerging as
      a compelling mechanism affecting the activities of significant transcription
      factors, including p53, FOXO or NF-kB. Smad proteins might be controlled by this
      mechanism, implying that accessory factors capable of altering Smads
      transcriptional complexes acetylation status and hence regulate TGFbeta responses
      remain to be identified. Understanding this interaction may help in the
      assessment of TGFbeta signaling outcomes, extending from healthy physiology to
      pathological conditions and cancer. METHODS: A two-hybrid chimera interacting
      system allowed to identify Sirt1, a NAD+ dependent type III histone deacetylase,
      as a novel Smad2 interactor. Several well stablished cellular models were applied
      to characterize this interaction by means of co-immunoprecipitation of tagged
      proteins and immuno-fluorescence staining. The occurrence of the interaction at
      Smad2 driven transcriptomic complexes was studied by means of DNA-pull-down and
      chromatin immunoprecipitation (ChIP), while its effects were assessed by protein
      over-expression and siRNA applied into a TGFbeta-dependent reporter gene assay.
      RESULTS: The interaction was confirmed and observed to be enhanced upon Smad2
      acetylation, a known feature of active and nuclear Smad2. However, Sirt1 did not
      play a major role in Smad2 deacetylation. Anti-Sirt1 ChIP showed increased
      recovery of promoter regions corresponding to Smad2-driven genes after TGFbeta
      stimulation, while its occurrence at Smad2-dependent transcriptomic complexes on
      DNA was found to effectively modulate gene expression. CONCLUSIONS: Sirt1
      presence on Smad2-driven TGFbeta-dependent regulatory elements was detected and
      found to increase after TGFbeta treatment. Moreover, Sirt1 overexpression
      resulted in a decrease of the activity of a Smad2-driven TGFbeta-dependent
      reporter gene, while Sirt1 interference increased its activity. This would
      confirm the relevance of the discovered Sirt1-Smad2 interaction for the
      regulation of TGFbeta-dependent gene transcription.

PMID- 29187202
TI  - Gene expression profiling in pbMEC - in search of molecular biomarkers to predict
      immunoglobulin production in bovine milk.
AB  - BACKGROUND: Optimization of the immunoglobulin (Ig) yield in bovine milk used as
      therapeutic immune milk or whey for the prevention of Clostridium difficile
      associated diarrhea in humans is of great importance to improve the economic
      efficiency of production. Individual dairy cows have diverse immune responses
      upon vaccination, resulting in a variable Ig yield in blood and milk. Therefore,
      it is advisable to pre-select cows with the best ability to produce and secrete
      high yields of specific Igs. RESULTS: The gene expression profile of pbMEC
      (primary bovine mammary epithelial cells), challenged with the gram-positive, non
      mastitis, pathogen Clostridium difficile showed distinct and significant
      differences in the gene expression of effector molecules of the innate immune
      system. A number of genes were identified that could possibly serve as molecular
      biomarkers to differentiate high responder cows from low responder cows. These
      identified genes play key roles in the promotion of innate immunity. CONCLUSION:
      Using a gene expression profiling approach, we showed that upon others,
      especially the gene expression of the pro-inflammatory cytokines was altered
      between the high and low responder cows. Those genes are indicated as potential
      molecular biomarkers in the pre-selection of cows that are able to secrete high
      immunoglobulin yields in milk.

PMID- 29187203
TI  - SoftHand at the CYBATHLON: a user's experience.
AB  - BACKGROUND: Roughly one-quarter of upper limb prosthesis users reject their
      prosthesis. Reasons for rejection range from comfort, to cost, aesthetics,
      function, and more. This paper follows a single user from training with and
      testing of a novel upper-limb myoelectric prosthesis (the SoftHand Pro) for
      participation in the CYBATHLON rehearsal to training for and competing in the
      CYBATHLON 2016 with a figure-of-nine harness controlled powered prosthesis
      (SoftHand Pro-H) to explore the feasibility and usability of a flexible
      anthropomorphic prosthetic hand. METHODS: The CYBATHLON pilot took part in
      multiple in-lab training sessions with the SoftHand Pro and SoftHand Pro-H; these
      sessions focused on basic control and use of the prosthetic devices and direct
      training of the tasks in the CYBATHLON. He used these devices in competition in
      the Powered Arm Prosthesis Race in the CYBATHLON rehearsal and 2016 events.
      RESULTS: In training for the CYBATHLON rehearsal, the subject was able to quickly
      improve performance with the myoelectric SHP despite typically using a body
      powered prosthetic hook. The subject improved further with additional training
      using the figure-of-nine harness-controlled SHPH in preparation for the
      CYBATHLON. The Pilot placed 3rd (out of 4) in the rehearsal. In the CYBATHLON, he
      placed 5th (out of 12) and was one of only two pilots who successfully completed
      all tasks in the competition, having the second-highest score overall.
      CONCLUSIONS: Results with the SoftHand Pro and Pro-H suggest it to be a viable
      alternative to existing anthropomorphic hands and show that the unique
      flexibility of the hand is easily learned and exploited.

PMID- 29187205
TI  - Combined double chambered right ventricle, tricuspid valve dysplasia, ventricular
      septal defect, and subaortic stenosis in a dog.
AB  - BACKGROUND: Double chambered right ventricle (DCRV) is a congenital heart anomaly
      where the right ventricle is divided into two chambers. We describe, for the
      first time, an unusual combination of DCRV combined with some other congenital
      heart defects. CASE PRESENTATION: A 1.2-year-old Golden Retriever was presented
      with lethargy, exercise intolerance and ascites. Physical examination revealed an
      irregularly irregular pulse and a grade V/VI, systolic, right cranial murmur.
      Electrocardiography revealed widened and splintered QRS complexes with a right
      bundle-branch block pattern. Radiography demonstrated right-sided cardiomegaly.
      Two-dimensional echocardiography identified a DCRV with tricuspid valve
      dysplasia. The patient died despite abdominocentesis and 4 days of oral
      pharmacotherapy, and necropsy revealed an anomalous fibromuscular structure that
      divided the right ventricle into two compartments. Another finding was tricuspid
      valve dysplasia with hypoplasia of the posterior and septal leaflets. The
      anterior leaflet was prominent, being part of the anomalous structure that
      divided the right ventricle. Necropsy also identified a perimembranous
      ventricular septal defect and mild subaortic stenosis. Histopathological
      examination of the fibromuscular band that separated the right ventricle
      identified longitudinally oriented layers of dense fibrous connective tissue and
      myocardial cells arranged in a plexiform pattern. The muscular component was well
      represented at the ventral area of the fibromuscular band, and was absent in the
      central zone. Superficially, the endocardium presented areas of nodular
      hyperplasia covering mainly the fibrous part of the abnormal structure. The
      nodules were sharply demarcated and were composed by loosely arranged connective
      tissue with myxoid appearance, covered by discrete hyperplastic endocardium.
      CONCLUSIONS: Concomitant cardiac malformations involving DCRV, tricuspid valve
      dysplasia, perimembranous ventricular septal defect and mild subaortic stenosis
      have not been previously described in veterinary medicine, and are reported here
      for the first time. Moreover, this is the first report of a canine patient with
      tricuspid valve dysplasia (TVD) and DCRV where the anterior leaflet is part of an
      anomalous structure dividing the right ventricle (RV) into two separate
      compartments.

PMID- 29187206
TI  - Multi-modality imaging evaluation of recurrent Tako-tsubo syndrome in a patient
      with coronary artery fibromuscular dysplasia.
AB  - BACKGROUND: Integrated bedside and sophisticated cardiac imaging techniques help
      characterize the discrepancy between myocardial injury and mechanic dysfunction
      in acute myocardial infarction. CASE PRESENTATION: A 57 year-old woman presented
      with sudden onset chest pain and ventricular fibrillation after hearing of her
      brother's death. The electrocardiography indicated "anterior wall ST segment
      elevation myocardial infarction". Coronary angiography ruled out obstructive
      lesion in the major coronary arteries, but revealed fibromuscular dysplasia of
      the distal left anterior descending artery. The ventriculography showed
      remarkable ventricular dilation, which affected much broader myocardium than the
      culprit vessel supplied. In a subsequent cardiac magnetic resonance study,
      delayed contrast (gadolinium) image revealed a focal left ventricular (LV) apical
      infarction. Her LV systolic function normalized within 1 week, except for a
      residual apical hypokinesis. She developed recurrent chest pain and LV dilation
      when she was laid off 9 months later. After supportive therapy, her symptoms
      improved and LV dysfunction normalized again. CONCLUSIONS: "Tako-tsubo" syndrome
      can occur recurrently in the heart with pre-existing localized myocardial
      infarction. Its molecular mechanism and clinical significance warrants further
      investigation.

PMID- 29187204
TI  - Experimental design and quantitative analysis of microbial community multiomics.
AB  - Studies of the microbiome have become increasingly sophisticated, and multiple
      sequence-based, molecular methods as well as culture-based methods exist for
      population-scale microbiome profiles. To link the resulting host and microbial
      data types to human health, several experimental design considerations, data
      analysis challenges, and statistical epidemiological approaches must be
      addressed. Here, we survey current best practices for experimental design in
      microbiome molecular epidemiology, including technologies for generating,
      analyzing, and integrating microbiome multiomics data. We highlight studies that
      have identified molecular bioactives that influence human health, and we suggest
      steps for scaling translational microbiome research to high-throughput target
      discovery across large populations.

PMID- 29187207
TI  - Metabolomic effects of CeO2, SiO2 and CuO metal oxide nanomaterials on HepG2
      cells.
AB  - BACKGROUND: To better assess potential hepatotoxicity of nanomaterials, human
      liver HepG2 cells were exposed for 3 days to five different CeO2 (either 30 or
      100 MUg/ml), 3 SiO2 based (30 MUg/ml) or 1 CuO (3 MUg/ml) nanomaterials with dry
      primary particle sizes ranging from 15 to 213 nm. Metabolomic assessment of
      exposed cells was then performed using four mass spectroscopy dependent platforms
      (LC and GC), finding 344 biochemicals. RESULTS: Four CeO2, 1 SiO2 and 1 CuO
      nanomaterials increased hepatocyte concentrations of many lipids, particularly
      free fatty acids and monoacylglycerols but only CuO elevated lysolipids and
      sphingolipids. In respect to structure-activity, we now know that five out of six
      tested CeO2, and both SiO2 and CuO, but zero out of four TiO2 nanomaterials have
      caused this elevated lipids effect in HepG2 cells. Observed decreases in UDP
      glucuronate (by CeO2) and S-adenosylmethionine (by CeO2 and CuO) and increased S
      adenosylhomocysteine (by CuO and some CeO2) suggest that a nanomaterial exposure
      increases transmethylation reactions and depletes hepatic methylation and
      glucuronidation capacity. Our metabolomics data suggests increased free radical
      attack on nucleotides. There was a clear pattern of nanomaterial-induced
      decreased nucleotide concentrations coupled with increased concentrations of
      nucleic acid degradation products. Purine and pyrimidine alterations included
      concentration increases for hypoxanthine, xanthine, allantoin, urate, inosine,
      adenosine 3',5'-diphosphate, cytidine and thymidine while decreases were seen for
      uridine 5'-diphosphate, UDP-glucuronate, uridine 5'-monophosphate, adenosine 5'
      diphosphate, adenosine 5'-monophophate, cytidine 5'-monophosphate and cytidine 3'
      monophosphate. Observed depletions of both 6-phosphogluconate, NADPH and NADH
      (all by CeO2) suggest that the HepG2 cells may be deficient in reducing
      equivalents and thus in a state of oxidative stress. CONCLUSIONS: Metal oxide
      nanomaterial exposure may compromise the methylation, glucuronidation and reduced
      glutathione conjugation systems; thus Phase II conjugational capacity of
      hepatocytes may be decreased. This metabolomics study of the effects of nine
      different nanomaterials has not only confirmed some observations of the prior
      2014 study (lipid elevations caused by one CeO2 nanomaterial) but also found some
      entirely new effects (both SiO2 and CuO nanomaterials also increased the
      concentrations of several lipid classes, nanomaterial induced decreases in S
      adenosylmethionine, UDP-glucuronate, dipeptides, 6-phosphogluconate, NADPH and
      NADH).

PMID- 29187208
TI  - Multiple markers, niche modelling, and bioregions analyses to evaluate the
      genetic diversity of a plant species complex.
AB  - BACKGROUND: The classification of closely related plants is not straightforward.
      These morphologically similar taxa frequently maintain their inter-hybridization
      potential and share ancestral polymorphisms as a consequence of their recent
      divergence. Under the biological species concept, they may thus not be considered
      separate species. The Petunia integrifolia complex is especially interesting
      because, in addition to the features mentioned above, its taxa share a
      pollinator, and their geographical ranges show multiple overlaps. Here, we
      combined plastid genome sequences, nuclear microsatellites, AFLP markers,
      ecological niche modelling, and bioregions analysis to investigate the genetic
      variability between the different taxa of the P. integrifolia complex in a
      comprehensive sample covering the entire geographical range of the complex.
      RESULTS: Results from molecular markers did not fully align with the current
      taxonomic classification. Niche modelling and bioregions analyses revealed that
      taxa were associated with different ecological constraints, indicating that the
      habitat plays an important role in preserving species boundaries. For three taxa,
      our analyses showed a mostly conserved, non-overlapping geographical distribution
      over time. However, for two taxa, niche modelling found an overlapping
      distribution over time; these taxa were also associated with the same bioregions.
      CONCLUSIONS: cpDNA markers were better able to discriminate between Petunia taxa
      than SSRs and AFLPs. Overall, our results suggest that the P. integrifolia
      complex represents a continuum of individuals from distant and historically
      isolated populations, which share some morphological traits, but are established
      in four different evolutionary lineages.

PMID- 29187209
TI  - Biodistribution of single and aggregated gold nanoparticles exposed to the human
      lung epithelial tissue barrier at the air-liquid interface.
AB  - BACKGROUND: The lung represents the primary entry route for airborne particles
      into the human body. Most studies addressed possible adverse effects using single
      (nano)particles, but aerosolic nanoparticles (NPs) tend to aggregate and form
      structures of several hundreds nm in diameter, changing the physico-chemical
      properties and interaction with cells. Our aim was to investigate how aggregation
      might affect the biodistribution; cellular uptake and translocation over time of
      aerosolized NPs at the air-blood barrier interface using a multicellular lung
      system. RESULTS: Model gold nanoparticles (AuNPs) were engineered and well
      characterized to compare single NPs with aggregated NPs with hydrodynamic
      diameter of 32 and 106 nm, respectively. Exposures were performed by
      aerosolization of the particles onto the air-liquid interface of a three
      dimensional (3D) lung model. Particle deposition, cellular uptake and
      translocation kinetics of single and aggregated AuNPs were determined for various
      concentrations, (30, 60, 150 and 300 ng/cm2) and time points (4, 24 and 48 h)
      using transmission electron microscopy and inductively coupled plasma optical
      emission spectroscopy. No apparent harmful effect for single and aggregated AuNPs
      was observed by lactate dehydrogenase assay, nor pro-inflammation response by
      tumor necrosis factor alpha assessment. The cell layer integrity was also not
      impaired. The bio-distribution revealed that majority of the AuNPs, single or
      aggregated, were inside the cells, and only a minor fraction, less than 5%, was
      found on the basolateral side. No significant difference was observed in the
      translocation rate. However, aggregated AuNPs showed a significantly faster
      cellular uptake than single AuNPs at the first time point, i.e. 4 h. CONCLUSIONS:
      Our studies revealed that aggregated AuNPs showed significantly faster cellular
      uptake than single AuNPs at the first time point, i.e. 4 h, but the uptake rate
      was similar at later time points. In addition, aggregation did not affect
      translocation rate across the lung barrier model since similar translocation
      rates were observed for single as well as aggregated AuNPs.

PMID- 29187210
TI  - State of newborn care in South Sudan's displacement camps: a descriptive study of
      facility-based deliveries.
AB  - BACKGROUND: Approximately 2.7 million neonatal deaths occur annually, with
      highest rates of neonatal mortality in countries that have recently experienced
      conflict. Constant instability in South Sudan further strains a weakened health
      system and poses public health challenges during the neonatal period. We aimed to
      describe the state of newborn facility-level care in displaced person camps
      across Juba, Malakal, and Maban. METHODS: We conducted clinical observations of
      the labor and delivery period, exit interviews with recently delivered mothers,
      health facility assessments, and direct observations of midwife time-use. Study
      participants were mother-newborn pairs who sought services and birth attendants
      who provided delivery services between April and June 2016 in five health
      facilities. RESULTS: Facilities were found to be lacking the recommended medical
      supplies for essential newborn care. Two of the five facilities had skilled
      midwives working during all operating hours, with 6.2% of their time spent on
      postnatal care. Selected components of thermal care (62.5%), infection prevention
      (74.8%), and feeding support (63.6%) were commonly practiced, but postnatal
      monitoring (27.7%) was less consistently observed. Differences were found when
      comparing the primary care level to the hospital (thermal: relative risk [RR]
      0.48 [95% CI] 0.40-0.58; infection: RR 1.28 [1.11-1.47]; feeding: RR 0.49 [0.40
      0.58]; postnatal: RR 3.17 [2.01-5.00]). In the primary care level, relative to
      newborns delivered by traditional birth attendants, those delivered by skilled
      attendants were more likely to receive postnatal monitoring (RR 1.59 [1.09
      2.32]), but other practices were not statistically different. Mothers' knowledge
      of danger signs was poor, with fever as the highest reported (44.8%) followed by
      not feeding well (41.0%), difficulty breathing (28.9%), reduced activity (27.7%),
      feeling cold (18.0%) and convulsions (11.2%). CONCLUSIONS: Addressing health
      service delivery in contexts affected by conflict is vital to reducing the global
      newborn mortality rate and reaching the Sustainable Development Goals. Gaps in
      intrapartum and postnatal care, particularly skilled care at birth, suggest a
      critical need to build the capacity of the existing health workforce while
      increasing access to skilled deliveries.

PMID- 29187211
TI  - Roles of KAI1 and nm23 in lymphangiogenesis and lymph metastasis of laryngeal
      squamous cell carcinoma.
AB  - BACKGROUND: Lymphatic metastasis contributes to the poor prognosis of laryngeal
      squamous cell carcinoma (LSCC). This study aimed to investigate the roles of two
      metastasis suppressor genes, KAI1 and nm23, in lymphangiogenesis and lymph
      metastasis of LSCC. METHODS: A total of 45 LSCC patients were enrolled in this
      study. The positive expression rates of KAI1 and nm23 protein were detected via
      immunohistochemistry in 45 LSCC and 22 normal laryngeal mucosa adjacent to LSCC.
      Micro-lymphatic vessel density (MLVD) was detected via immunohistochemistry with
      the specific antibody D2-40. Associations between KAI1 and nm23 expression and
      clinical characteristics of LSCC were then evaluated. RESULTS: The positive
      expression rates of KAI1 and nm23 were significantly lower in LSCC than normal
      laryngeal mucosa (P < 0.05). Significantly lower positive rates of KAI1 and nm23
      were found in LSCC with lymphatic metastasis than those without lymphatic
      metastasis (P < 0.05), whereas MLVD was negatively correlated with the expression
      of KAI1 and nm23 (P < 0.05). However, no significant associations were found
      between KAI1 and nm23 expression and clinical characteristics of LSCC (sex, age,
      disease position, differentiation, and T-stage). CONCLUSIONS: Both KAI1 and nm23
      can inhibit lymphangiogenesis and lymphatic metastasis in LSCC.

PMID- 29187212
TI  - Roles of Bronchopulmonary C-fibers in airway Hyperresponsiveness and airway
      remodeling induced by house dust mite.
AB  - BACKGROUND: Asthma is characterized by chronic airway inflammation, airway
      hyperresponsiveness (AHR), and airway remodeling. While exposure of house dust
      mites (HDM) is a common cause of asthma, the pathogenesis of the HDM-induced
      asthma is not fully understood. Bronchopulmonary C-fibers (PCFs) contribute to
      the neurogenic inflammation, viral infection induced-persistent AHR, and
      ovalbumin induced collagen deposition largely via releasing neuropeptides, such
      as substance P (SP). However, PCF roles in the pathogenesis of the HDM-induced
      asthma remain unexplored. The goal of this study was to determine what role PCFs
      played in generating these characteristics. METHODS: We compared the following
      variables among the PCF-intact and -degenerated BALB/c mice with and without
      chronic HDM exposure (four groups): 1) AHR and pulmonary SP; 2) airway smooth
      muscle (ASM) mass; 3) pulmonary inflammatory cells; and 4) epithelium thickening
      and mucus secretion. RESULTS: We found that HDM evoked AHR associated with
      upregulation of pulmonary SP and inflammation, ASM mass increase, epithelium
      thickenings, and mucus hypersecretion. PCF degeneration decreased the HDM-induced
      changes in AHR, pulmonary SP and inflammation, and ASM mass, but failed to
      significantly affect the epithelium thickening and mucus hypersecretion.
      CONCLUSION: Our data suggest an involvement of PCFs in the mechanisms by which
      HDM induces allergic asthma via airway inflammation, AHR, and airway remodeling.

PMID- 29187213
TI  - JMJD6 promotes melanoma carcinogenesis through regulation of the alternative
      splicing of PAK1, a key MAPK signaling component.
AB  - BACKGROUND: Melanoma, originated from melanocytes located on the basal membrane
      of the epithelial tissue, is the most aggressive form of skin cancer that
      accounts for 75% of skin cancer-related death. Although it is believed that BRAF
      mutation and the mitogen-activated protein kinase (MAPK) pathway play critical
      roles in the pathogenesis of melanoma, how the MAPK signaling is regulated in
      melanoma carcinogenesis is still not fully understood. METHODS: We characterized
      JMJD6 expression in melanoma tissue array by immunohistochemistry analysis. We
      used human melanoma A375, 451Lu and SK-MEL-1 cell lines for in vitro
      proliferation and invasion experiments, and xenograft transplanted mice using
      murine melanoma B16F10 cells by bioluminescence imaging for in vivo tumor growth
      and pulmonary metastasis assessments. Endothelial tube formation assay, chicken
      yolk sac membrane assay and matrigel plug assay were performed to test the effect
      of JMJD6 on the angiogenic potential in vitro and in vivo. RESULTS: Here we
      report that the jumonji C domain-containing demethylase/hydroxylase JMJD6 is
      markedly up-regulated in melanoma. We found that high expression of JMJD6 is
      closely correlated with advanced clinicopathologic stage, aggressiveness, and
      poor prognosis of melanoma. RNA-seq showed that knockdown of JMJD6 affects the
      alternative splicing of a panel of transcripts including that encoding for PAK1,
      a key component in MAPK signaling pathway. We demonstrated that JMJD6 enhances
      the MAPK signaling and promotes multiple cellular processes including
      melanogenesis, proliferation, invasion, and angiogenesis in melanoma cells.
      Interestingly, JMJD6 is transcriptionally activated by c-Jun, generating a
      feedforward loop to drive the development and progression of melanoma.
      CONCLUSIONS: Our results indicate that JMJD6 is critically involved in melanoma
      carcinogenesis, supporting the pursuit of JMJD6 as a potential biomarker for
      melanoma aggressiveness and a target for melanoma intervention.

PMID- 29187214
TI  - Synthetic enhancer design by in silico compensatory evolution reveals flexibility
      and constraint in cis-regulation.
AB  - BACKGROUND: Models that incorporate specific chemical mechanisms have been
      successful in describing the activity of Drosophila developmental enhancers as a
      function of underlying transcription factor binding motifs. Despite this, the
      minimum set of mechanisms required to reconstruct an enhancer from its
      constituent parts is not known. Synthetic biology offers the potential to test
      the sufficiency of known mechanisms to describe the activity of enhancers, as
      well as to uncover constraints on the number, order, and spacing of motifs.
      RESULTS: Using a functional model and in silico compensatory evolution, we
      generated putative synthetic even-skipped stripe 2 enhancers with varying degrees
      of similarity to the natural enhancer. These elements represent the evolutionary
      trajectories of the natural stripe 2 enhancer towards two synthetic enhancers
      designed ab initio. In the first trajectory, spatially regulated expression was
      maintained, even after more than a third of binding sites were lost. In the
      second, sequences with high similarity to the natural element did not drive
      expression, but a highly diverged sequence about half the length of the minimal
      stripe 2 enhancer drove ten times greater expression. Additionally, homotypic
      clusters of Zelda or Stat92E motifs, but not Bicoid, drove expression in
      developing embryos. CONCLUSIONS: Here, we present a functional model of gene
      regulation to test the degree to which the known transcription factors and their
      interactions explain the activity of the Drosophila even-skipped stripe 2
      enhancer. Initial success in the first trajectory showed that the gene regulation
      model explains much of the function of the stripe 2 enhancer. Cases where
      expression deviated from prediction indicates that undescribed factors likely act
      to modulate expression. We also showed that activation driven Bicoid and
      Hunchback is highly sensitive to spatial organization of binding motifs. In
      contrast, Zelda and Stat92E drive expression from simple homotypic clusters,
      suggesting that activation driven by these factors is less constrained.
      Collectively, the 40 sequences generated in this work provides a powerful
      training set for building future models of gene regulation.

PMID- 29187216
TI  - Use of a flowable haemostat versus an oxidised regenerated cellulose agent in
      primary elective cardiac surgery: economic impact from a UK healthcare
      perspective.
AB  - BACKGROUND: Flowable haemostatic agents have been shown to be superior to non
      flowable agents in terms of haemostatic control and need for transfusion products
      in patients undergoing cardiac surgery. We investigated the economic impact of
      the use of a flowable haemostatic agent (Floseal) compared with non-flowable
      oxidised regenerated cellulose (ORC) agent in primary elective cardiac surgery
      from the perspective of the UK National Health Service (NHS). METHODS: A cost
      consequence framework based upon clinical data from a prospective trial and an
      observational trial and NHS-specific actual reference costs (2016) was developed
      to compare the economic impact of Floseal with that of ORC. The individual
      domains of care investigated comprised complications (major and minor) avoided,
      operating room time savings, surgical revisions for bleeding avoided and
      transfusions avoided. The cost impact of Floseal versus ORC on ICU days and
      extended bed days avoided was modelled separately. RESULTS: Compared with ORC,
      the use of Floseal would be associated with overall net savings to the NHS of
      L178,283 per 100 cardiac surgery patients who experience intraoperative bleeding
      requiring haemostatic therapy. Cost savings were apparent in all individual
      domains of care (complications avoided: L83,536; operating room time saved:
      L63,969; surgical revisions avoided: L34,038; and blood transfusions avoided:
      L22,317). Cost savings per 100 patients with Floseal over ORC in terms of ICU
      days avoided (n = 30) and extended bed days avoided (n = 51.7) were L57,960 and
      L21,965, respectively. A sensitivity analysis indicated that these findings
      remained robust when the model parameters representing the clinical benefit of
      Floseal over ORC were reduced by up to 20%. CONCLUSIONS: Despite higher initial
      acquisition costs, the use of flowable haemostatic agents achieves substantial
      cost savings over non-flowable agents in cardiac surgery. These cost savings
      commence during the operating theatre and appear to continue to be realised
      throughout the postoperative period.

PMID- 29187215
TI  - Criteria for identifying the molecular basis of the engram (CaMKII, PKMzeta).
AB  - The engram refers to the molecular changes by which a memory is stored in the
      brain. Substantial evidence suggests that memory involves learning-dependent
      changes at synapses, a process termed long-term potentiation (LTP). Thus,
      understanding the storages process that underlies LTP may provide insight into
      how the engram is stored. LTP involves induction, maintenance (storage), and
      expression sub-processes; special tests are required to specifically reveal
      properties of the storage process. The strongest of these is the Erasure test in
      which a transiently applied agent that attacks a putative storage molecule may
      lead to persistent erasure of previously induced LTP/memory. Two major hypotheses
      have been proposed for LTP/memory storage: the CaMKII and PKM-zeta hypotheses.
      After discussing the tests that can be used to identify the engram (Necessity
      test, Saturation/Occlusion test, Erasure test), the status of these hypotheses is
      evaluated, based on the literature on LTP and memory-guided behavior. Review of
      the literature indicates that all three tests noted above support the CaMKII
      hypothesis when done at both the LTP level and at the behavioral level. Taken
      together, the results strongly suggest that the engram is stored by an LTP
      process in which CaMKII is a critical memory storage molecule.

PMID- 29187218
TI  - Open stent graft repair with upper-half Sternotomy for blunt thoracic aortic
      injury: a case report.
AB  - BACKGROUND: Thoracic endovascular aortic repair is now widely applied to the
      treatment of blunt aortic injury. However, its long-term outcomes remain unclear.
      Endoleakage and migration might occur in the long term, especially when younger
      patients undergo endovascular aortic repair. In open stent grafting, the proximal
      end of the open stent graft is directly sutured to the native aorta, which may
      reduce the risk of endoleakage and migration. We applied open stent grafting to
      the treatment of blunt aortic injury in the subacute phase and herein report the
      patient's clinical course. CASE PRESENTATION: A 20-year-old man with a
      developmental disorder collided with a steel tower while skiing. He was
      transferred to our hospital by helicopter. X-ray examination and computed
      tomography revealed fractures of left humeral head and femoral neck and aortic
      isthmus dissection. We did not perform an acute-phase operation because of the
      presence of multiple trauma and instead performed open stent grafting with an
      upper-half sternotomy 42 days after the injury. He recovered uneventfully without
      psychological problems other than his preexisting developmental disorder. No
      endoleakage or aneurysm was observed during an 18-month follow-up period.
      CONCLUSIONS: Open stent grafting might be an alternative to open surgery and
      thoracic endovascular aortic repair for blunt chest trauma, although intensive
      follow-up is needed.

PMID- 29187217
TI  - The effects of care bundles on patient outcomes: a systematic review and meta
      analysis.
AB  - BACKGROUND: Care bundles are a set of three to five evidence-informed practices
      performed collectively and reliably to improve the quality of care. Care bundles
      are used widely across healthcare settings with the aim of preventing and
      managing different health conditions. This is the first systematic review
      designed to determine the effects of care bundles on patient outcomes and the
      behaviour of healthcare workers in relation to fidelity with care bundles.
      METHODS: This systematic review is reported in line with the PRISMA statement for
      reporting systematic reviews and meta-analyses. A total of 5796 abstracts were
      retrieved through a systematic search for articles published between January 1,
      2001, to February 4, 2017, in the Cochrane Central Register for Controlled
      Trials, MEDLINE, EMBASE, British Nursing Index, CINAHL, PsychInfo, British
      Library, Conference Proceeding Citation Index, OpenGrey trials (including cluster
      randomised trials) and non-randomised studies (comprising controlled before-after
      studies, interrupted time series, cohort studies) of care bundles for any health
      condition and any healthcare settings were considered. Following the removal of
      duplicated studies, two reviewers independently screen 3134 records. Three
      authors performed data extraction independently. We compared the care bundles
      with usual care to evaluate the effects of care bundles on the risk of negative
      patient outcomes. Random-effect models were used to further explore the effects
      of subgroups. RESULTS: In total, 37 studies (6 randomised trials, 31 controlled
      before-after studies) were eligible for inclusion. The effect of care bundles on
      patient outcomes is uncertain. For randomised trial data, the pooled relative
      risk of negative effects between care bundle and control groups was 0.97 [95% CI
      0.71 to 1.34; 2049 participants]. The relative risk of negative patient outcomes
      from controlled before-after studies favoured the care bundle treated groups
      (0.66 [95% CI 0.59 to 0.75; 119,178 participants]). However, using GRADE, we
      assessed the certainty of all of the evidence to be very low (downgraded for risk
      of bias, inconsistency, indirectness). CONCLUSIONS: Very low quality evidence
      from controlled before-after studies suggests that care bundles may reduce the
      risk of negative outcomes when compared with usual care. By contrast, the better
      quality evidence from six randomised trials is more uncertain. TRIAL
      REGISTRATION: PROSPERO, CRD42016033175.

PMID- 29187219
TI  - Re-irradiation for recurrent glioma- the NCI experience in tumor control, OAR
      toxicity and proposal of a novel prognostic scoring system.
AB  - PURPOSE/OBJECTIVES: Despite mounting evidence for the use of re-irradiation (re
      RT) in recurrent high grade glioma, optimal patient selection criteria for re-RT
      remain unknown. We present a novel scoring system based on radiobiology
      principles including target independent factors, the likelihood of target
      control, and the anticipated organ at risk (OAR) toxicity to allow for proper
      patient selection in the setting of recurrent glioma. MATERIALS/METHODS: Thirty
      one patients with recurrent glioma who received re-RT (2008-2016) at NCI - NIH
      were included in the analysis. A novel scoring system for overall survival (OS)
      and progression free survival (PFS) was designed to include:1) target independent
      factors (age, KPS (Karnofsky Performance Status), histology, presence of
      symptoms), 2) target control, and 3) OAR toxicity risk. Normal tissue
      complication probability (NTCP) calculations were performed using the Lyman
      model. Kaplan-Meier analysis was performed for overall survival (OS) and
      progression free survival (PFS) for comparison amongst variables. RESULTS: No
      patient, including those who received dose to OAR above the published tolerance
      dose, experienced any treatment related grade 3-5 toxicity with a median PFS and
      OS from re-RT of 4 months (0.5-103) and 6 months (0.7-103) respectively. Based on
      cumulative maximum doses the average NTCP was 25% (0-99%) for the chiasm, 21% (0
      99%) for the right optic nerve, 6% (0-92%) for the left optic nerve, and 59% (0
      100%) for the brainstem. The independent factor and target control scores were
      each statistically significant for OS and the combination of independent factors
      plus target control was also significant for both OS (p = 0.02) and PFS (p =
      0.006). The anticipated toxicity risk score was not statistically significant.
      CONCLUSION: Our scoring system may represent a novel approach to patient
      selection for re-RT in recurrent high grade glioma. Further validation in larger
      patient cohorts including compilation of doses to tumor and OAR may help refine
      this further for inclusion into clinical trials and general practice.

PMID- 29187220
TI  - Genomic copy number variation analysis in multiple system atrophy.
AB  - Genomic variation includes single-nucleotide variants, small insertions or
      deletions (indels), and copy number variants (CNVs). CNVs affect gene expression
      by altering the genome structure and transposable elements within a region. CNVs
      are greater than 1 kb in size; hence, CNVs can produce more variation than can
      individual single-nucleotide variations that are detected by next-generation
      sequencing. Multiple system atrophy (MSA) is an alpha-synucleinopathy adult-onset
      disorder. Pathologically, it is characterized by insoluble aggregation of
      filamentous alpha-synuclein in brain oligodendrocytes. Generally, MSA is
      sporadic, although there are rare cases of familial MSA. In addition, the
      frequencies of the clinical phenotypes differ considerably among countries.
      Reports indicate that genetic factors play roles in the mechanisms involved in
      the pathology and onset of MSA. To evaluate the genetic background of this
      disorder, we attempted to determine whether there are differences in CNVs between
      patients with MSA and normal control subjects. We found that the number of CNVs
      on chromosomes 5, 22, and 4 was increased in MSA; 3 CNVs in non-coding regions
      were considered risk factors for MSA. Our results show that CNVs in non-coding
      regions influence the expression of genes through transcription-related
      mechanisms and potentially increase subsequent structural alterations of
      chromosomes. Therefore, these CNVs likely play roles in the molecular mechanisms
      underlying MSA.

PMID- 29187222
TI  - Unusual presentation of plasmablastic lymphoma involving ovarian mature cystic
      teratoma: a case report.
AB  - BACKGROUND: Plasmablastic lymphoma (PBL) is relatively new clinical entity
      described as a distinct subtype of diffuse large B-cell lymphoma (DLBCL). It is
      characterized by its aggressive nature and proliferation of large neoplastic
      cells resembling immunoblasts including cells with more obvious plasmacytic
      differentiation. In this case report, we describe an unexpected finding of PBL
      associated with a mature cystic teratoma of the ovary in a young immune competent
      woman. CASE PRESENTATION: A 19-year old woman was admitted to the hospital with
      generalized lymphadenopathy, a pelvic tumor mass measuring 35 * 30 cm and a 4 cm
      lump in her right breast. She underwent a right salpingo-oophorectomy,
      lymphadenectomy, splenectomy, omentectomy, and a right breast lumpectomy. On
      macroscopic examination the right ovary was replaced by a thick-walled
      multilocular cystic tumor. Upon incision, the cysts were filled with thick,
      greasy sebaceous material and hair and there were several solid nodules within
      the cyst walls. Histological examination revealed a mature cystic teratoma and
      malignant non-Hodgkin lymphoma (NHL) within the solid nodules. Tumor tissue from
      the right breast, spleen and lymph nodes, all had the same histological, NHL
      morphology. After extensive immunostaining, a diagnosis of PBL was made.
      Following surgery, the patient was treated with different chemotherapy regimens,
      without any significant regression of the disease, and died of multiple organ
      failure. CONCLUSIONS: Primary NHL of the ovary is relatively rare occurrence
      while secondary involvement by lymphoma is much more common. PBL is a rare
      lymphoma, primarily reported in the jaw and oral mucosa, but also documented in
      extra-oral sites. To the best of our knowledge, this is the first case described
      in a mature ovarian cystic teratoma. Although the patient was HIV-negative and
      immune competent, she had progressive disease and died despite aggressive
      chemotherapy 11 months after the initial diagnosis.

PMID- 29187221
TI  - Autophagy maintains the stemness of ovarian cancer stem cells by FOXA2.
AB  - BACKGROUND: Cancer stem cells (CSCs) are regarded as the main cell type
      responsible for the initiation, metastasis, drug resistance, and recurrence of
      cancer. But the mechanism by which cancer stem cells maintain their stemness
      remains unclear. METHODS AND RESULTS: In the present study, ovarian cancer stem
      cells (OCSCs) were revealed to have an enhanced autophagic flux. Furthermore,
      their chemoresistance and ability to self-renewal in vitro were decreased when
      autophagy was inhibited by Bafilomycin A1(BafA1), Chloroquine(CQ) or autophagy
      related 5(ATG5) knockdown. PCR array screening determined that Forkhead Box
      A2(FOXA2) was highly expressed in OCSCs, and correspondingly regulated by
      autophagy activity. In addition, the self-renewal ability was decreased in the
      case of FOXA2 knockdown by shRNA in OCSCs. Overexpression of FOXA2 from the
      pEGFP(+)-FOXA2 plasmid partially reversed the depressed self-renewal ability of
      OCSCs during autophagy inhibition. CONCLUSIONS: Our findings suggest that
      autophagy, through participation of FOXA2, maintains the characteristics of
      OCSCs. Autophagy and FOXA2 are therefore potential targets for ovarian cancer
      stem cell directed therapies.

PMID- 29187224
TI  - Correction to: FLAGS, frequently mutated genes in public exomes.
AB  - CORRECTION: Unfortunately, the original article [1] contained an error. The
      additional files were included incorrectly. The correct additional files 1, 2, 3,
      4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14 are published in this correction.

PMID- 29187223
TI  - The 3' end of the story: deciphering combinatorial interactions that control mRNA
      fate.
AB  - A new study investigates how microRNAs affect the binding of proteins to RNA.

PMID- 29187225
TI  - Robotic sleeve lobectomy with four arms for lung cancer centrally located in the
      right lower lobe: a case report.
AB  - Sleeve lobectomy can preserve healthy lung parenchyma in centrally located lung
      cancer surgery. Video-assisted thoracoscopic surgery (VATS) lobectomy has been
      shown to have better results for postoperative complications than thoracotomy
      lobectomy. However, its limitations in visualization of operative field and
      handling of instruments restrain surgeons performing sleeve lobectomy. Robotic
      surgery has several advantages, including magnified 3-dimensional vision and
      angulation of the robot arm that can provide better circumstances for sleeve
      lobectomy than VATS. However, robotic sleeve lobectomy has been rarely reported.
      Here, we describe our experience of performing robotic sleeve lobectomy using
      four arms for lung cancer centrally located in the right lower lobe.

PMID- 29187226
TI  - Development and pilot testing of an informed consent video for patients with limb
      trauma prior to debridement surgery using a modified Delphi technique.
AB  - BACKGROUND: Ensuring adequate informed consent for surgery in a trauma setting is
      challenging. We developed and pilot tested an educational video containing
      information regarding the informed consent process for surgery in trauma patients
      and a knowledge measure instrument and evaluated whether the audiovisual
      presentation improved the patients' knowledge regarding their procedure and
      aftercare and their satisfaction with the informed consent process. METHODS: A
      modified Delphi technique in which a panel of experts participated in successive
      rounds of shared scoring of items to forecast outcomes was applied to reach a
      consensus among the experts. The resulting consensus was used to develop the
      video content and questions for measuring the understanding of the informed
      consent for debridement surgery in limb trauma patients. The expert panel
      included experienced patients. The participants in this pilot study were enrolled
      as a convenience sample of adult trauma patients scheduled to receive surgery.
      RESULTS: The modified Delphi technique comprised three rounds over a 4-month
      period. The items given higher scores by the experts in several categories were
      chosen for the subsequent rounds until consensus was reached. The experts reached
      a consensus on each item after the three-round process. The final knowledge
      measure comprising 10 questions was developed and validated. Thirty eligible
      trauma patients presenting to the Emergency Department (ED) were approached and
      completed the questionnaires in this pilot study. The participants exhibited
      significantly higher mean knowledge and satisfaction scores after watching the
      educational video than before watching the video. CONCLUSIONS: Our process is
      promising for developing procedure-specific informed consent and audiovisual aids
      in medical and surgical specialties. The educational video was developed using a
      scientific method that integrated the opinions of different stakeholders,
      particularly patients. This video is a useful tool for improving the knowledge
      and satisfaction of trauma patients in the ED. The modified Delphi technique is
      an effective method for collecting experts' opinions and reaching a consensus on
      the content of educational materials for informed consent. Institutions should
      prioritize patient-centered health care and develop a structured informed consent
      process to improve the quality of care. TRIAL REGISTRATION: The
      ClinicalTrials.gov Identifier is NCT01338480 . The date of registration was April
      18, 2011 (retrospectively registered).

PMID- 29187228
TI  - RNAs: dynamic and mutable.

PMID- 29187227
TI  - Obesity reversibly depletes the basal cell population and enhances mammary
      epithelial cell estrogen receptor alpha expression and progenitor activity.
AB  - BACKGROUND: Obesity is correlated with an increased risk for developing
      postmenopausal breast cancer. Since obesity rates continue to rise worldwide, it
      is important to understand how the obese microenvironment influences normal
      mammary tissue to increase breast cancer risk. We hypothesized that obesity
      increases the proportion of luminal progenitor cells, which are thought to be the
      cells of origin for the most common types of breast cancer, potentially leading
      to an increased risk for breast cancer. METHODS: To study the obese
      microenvironment within the mammary gland, we used a high-fat diet mouse model of
      obesity and human breast tissue from reduction mammoplasty surgery. We identified
      changes in breast epithelial cell populations using flow cytometry for cell
      surface markers, in vitro functional assays and expression of markers on breast
      tissue sections. RESULTS: In both obese female mice and women, mammary epithelial
      cell populations demonstrated significant decreases in basal/myoepithelial cells,
      using either flow cytometry or cell-type-specific markers (SMA and p63). Estrogen
      receptor alpha (ERalpha) expression was significantly increased in luminal cells
      in obese mammary tissue, compared with control mice or breast tissue from lean
      women. Functional assays demonstrated significantly enhanced mammary epithelial
      progenitor activity in obese mammary epithelial cells and elevated numbers of
      ERalpha-positive epithelial cells that were co-labeled with markers of
      proliferation. Weight loss in a group of obese mice reversed increases in
      progenitor activity and ERalpha expression observed in obese mammary tissue.
      CONCLUSIONS: Obesity enhances ERalpha-positive epithelial cells, reduces the
      number of basal/myoepithelial cells, and increases stem/progenitor activity
      within normal mammary tissue in both women and female mice. These changes in
      epithelial cell populations induced by obesity are reversible with weight loss.
      Our findings support further studies to examine how obesity-induced changes in
      stem/progenitor cells impact breast tumor incidence and histologic tumor types.

PMID- 29187229
TI  - Optimal RNA isolation method and primer design to detect gene knockdown by qPCR
      when validating Drosophila transgenic RNAi lines.
AB  - OBJECTIVE: RNA interference is employed extensively in Drosophila research to
      study gene function within a specific cell-type or tissue. Thousands of
      transgenic Drosophila lines have been generated to express double stranded RNA
      for gene knockdown; however, no standardized method exists for quantifying their
      knockdown efficiency. Since antibodies are not available for many proteins,
      quantitative real-time PCR is often used. Here, we explore how primer design and
      RNA isolation method can influence detection of gene knockdown using qPCR.
      RESULTS: We tested differences in detected gene knockdown efficiency when using
      purified polyadenylated mRNA or total RNA as templates for cDNA synthesis. We
      also tested two different primer locations for each gene: one to amplify a region
      5' of the RNAi cut site, and one to amplify a region 3' of the cut site.
      Consistently, the strongest gene knockdown was detected when qPCR was performed
      using 5' primer sets in combination with mRNA-derived cDNA. Our results indicate
      that detection of undegraded mRNA cleavage fragments can result in
      underestimation of true knockdown efficiency for a RNAi construct. Purification
      of polyadenylated mRNA, combined with primers designed to amplify the non
      polyadenylated 5' mRNA cleavage fragment can avoid this problem.

PMID- 29187230
TI  - Decreasing Delirium through Music (DDM) in critically ill, mechanically
      ventilated patients in the intensive care unit: study protocol for a pilot
      randomized controlled trial.
AB  - BACKGROUND: Delirium is a highly prevalent and morbid syndrome in intensive care
      units (ICUs). Changing the stressful environment within the ICU via music may be
      an effective and a scalable way to reduce the burden of delirium. METHODS/DESIGN:
      The Decreasing Delirium through Music (DDM) study is a three-arm, single-blind,
      randomized controlled feasibility trial. Sixty patients admitted to the ICU with
      respiratory failure requiring mechanical ventilation will be randomized to one of
      three arms (20 participants per arm): (1) personalized music, (2) non
      personalized relaxing music, or (3) attention-control. Music preferences will be
      obtained from all enrolled participants or their family caregivers. Participants
      will receive two 1-h audio sessions a day through noise-cancelling headphones and
      mp3 players. Our primary aim is to determine the feasibility of the trial design
      (recruitment, adherence, participant retention, design and delivery of the music
      intervention). Our secondary aim is to estimate the potential effect size of
      patient-preferred music listening in reducing delirium, as measured by the
      Confusion Assessment Method for the ICU (CAM-ICU). Participants will receive
      twice daily assessments for level of sedation and presence of delirium. Enrolled
      participants will be followed in the hospital until death, discharge, or up to 28
      days, and seen in the Critical Care Recovery Clinic at 90 days. DISCUSSION: DDM
      is a feasibility trial to provide personalized and non-personalized music
      interventions for critically ill, mechanically ventilated patients. Our trial
      will also estimate the preliminary efficacy of music interventions on reducing
      delirium incidence and severity. TRIAL REGISTRATION: ClinicalTrials.gov,
      Identifier: NCT03095443 . Registered on 23 March 2017.

PMID- 29187231
TI  - Post encephalitic parkinsonism following dengue viral infection.
AB  - BACKGROUND: Incidence of dengue fever as well as dengue hemorrhagic fever is
      increasing in Sri Lanka especially among elderly population. As the number of
      cases is rising, rare complications of dengue illness also can be seen in
      clinical practice when compared to the past few years. Prompt identification and
      treatment of such complications is challenging due to lack of awareness and
      unavailability of standard treatment. CASE PRESENTATION: 69 years old man
      presented with acute onset fever and was diagnosed as having dengue illness. On
      the 4th day of illness, the disease was progressed into dengue haemorrhagic fever
      and recovered uneventfully. Although he recovered from primary illness, his
      general condition continued to deteriorate due to new onset of features of
      parkinsonism. Cerebrospinal fluid analysis and electro encephalogram showed
      evidence of encephalitis. Cerebrospinal fluid analysis also revealed positive IgM
      antibodies against dengue virus. Then the diagnosis of post encephalitic
      parkinsonism following dengue viral infection was made and started on. He was
      started on SINEMET (carbidopa 10 mg and levodopa 100 mg) half tablet 6 hourly
      started. After 1 week of treatment he showed marked improvement and then patient
      was discharged with further follow up plan. CONCLUSION: Although the management
      of dengue illness and dengue haemorrhagic fever is straightforward, recognition
      and treatment of rare complications like post encephalitic parkinsonism following
      dengue viral infection is difficult without great clinical suspicion.

PMID- 29187232
TI  - Long-term continuous renal replacement therapy and anticoagulation with citrate
      in critically ill patients with severe liver dysfunction.
AB  - BACKGROUND: As of 2009, anticoagulation with citrate was standard practice in
      continuous renal replacement therapy (CRRT) for critically ill patients at the
      University Medical Centre of Saarland, Germany. Partial hepatic metabolism of
      citrate means accumulation may occur during CRRT in critically ill patients with
      impaired liver function. The aim of this study was to evaluate the actual
      influence of hepatic function on citrate-associated complications during long
      term CRRT. METHODS: In a retrospective study conducted between January 2009 and
      November 2012, all cases of dialysis therapy performed in the interdisciplinary
      surgical intensive care unit were analysed. Inclusion criteria were CRRT and
      regional anticoagulation with citrate, pronounced liver dysfunction, and
      pathologically reduced indocyanine green plasma disappearance rate (ICG-PDR).
      RESULTS: A total of 1339 CRRTs were performed in 69 critically ill patients with
      liver failure. At admission, the mean Model for End-stage Liver Disease score was
      19.2, and the mean ICG-PDR was 9.8%. Eight patients were treated with liver
      replacement therapy, and 30 underwent transplants. The mortality rate was 40%.
      The mean duration of dialysis was 19.4 days, and the circuit patency was 62.2 h.
      Accumulation of citrate was detected indirectly by total serum calcium/ionised
      serum calcium (tCa/iCa) ratio > 2.4. This was noted in 16 patients (23.2%).
      Dialysis had not to be discontinued for metabolic disorder or accumulation of
      citrate in any case. In 26% of cases, metabolic alkalosis occurred with pH > 7.5.
      Interestingly, no correlation between citrate accumulation and liver function
      parameters was detected. Moreover, most standard laboratory liver function
      parameters showed poor predictive capabilities for accumulation of citrate.
      CONCLUSIONS: Our findings indicate that extra-hepatic metabolism of citrate seems
      to exist, avoiding in most cases citrate accumulation in critically ill patients
      despite impaired liver function. Because the citric acid cycle is oxygen
      dependent, disturbed microcirculation would result in inadequate citrate
      metabolism. Raising the tCa/iCa ratio would therefore be an indicator of severity
      of illness and mortality rather than of liver failure. However, further studies
      are warranted for confirmation.

PMID- 29187234
TI  - COGcollator: a web server for analysis of distant relationships between
      homologous protein families.
AB  - BACKGROUND: The Clusters of Orthologous Groups (COGs) of proteins systematize
      evolutionary related proteins into specific groups with similar functions.
      However, the available databases do not provide means to assess the extent of
      similarity between the COGs. AIM: We intended to provide a method for
      identification and visualization of evolutionary relationships between the COGs,
      as well as a respective web server. RESULTS: Here we introduce the COGcollator, a
      web tool for identification of evolutionarily related COGs and their further
      analysis. We demonstrate the utility of this tool by identifying the COGs that
      contain distant homologs of (i) the catalytic subunit of bacterial rotary
      membrane ATP synthases and (ii) the DNA/RNA helicases of the superfamily 1.
      REVIEWERS: This article was reviewed by Drs. Igor N. Berezovsky, Igor Zhulin and
      Yuri Wolf.

PMID- 29187233
TI  - Identification of O-GlcNAcylated proteins in Plasmodium falciparum.
AB  - BACKGROUND: Post-translational modifications (PTMs) constitute a huge group of
      chemical modifications increasing the complexity of the proteomes of living
      beings. PTMs have been discussed as potential anti-malarial drug targets due to
      their involvement in many cell processes. O-GlcNAcylation is a widespread PTM
      found in different organisms including Plasmodium falciparum. The aim of this
      study was to identify O-GlcNAcylated proteins of P. falciparum, to learn more
      about the modification process and to understand its eventual functions in the
      Apicomplexans. METHODS: The P. falciparum strain 3D7 was amplified in
      erythrocytes and purified. The proteome was checked for O-GlcNAcylation using
      different methods. The level of UDP-GlcNAc, the donor of the sugar moiety for O
      GlcNAcylation processes, was measured using high-pH anion exchange
      chromatography. O-GlcNAcylated proteins were enriched and purified utilizing
      either click chemistry labelling or adsorption on succinyl-wheat germ agglutinin
      beads. Proteins were then identified by mass-spectrometry (nano-LC MS/MS).
      RESULTS: While low when compared to MRC5 control cells, P. falciparum disposes of
      its own pool of UDP-GlcNAc. By using proteomics methods, 13 O-GlcNAcylated
      proteins were unambiguously identified (11 by click-chemistry and 6 by sWGA-beads
      enrichment; 4 being identified by the 2 approaches) in late trophozoites. These
      proteins are all part of pathways, functions and structures important for the
      parasite survival. By probing clicked-proteins with specific antibodies, Hsp70
      and alpha-tubulin were identified as P. falciparum O-GlcNAc-bearing proteins.
      CONCLUSIONS: This study is the first report on the identity of P. falciparum O
      GlcNAcylated proteins. While the parasite O-GlcNAcome seems close to those of
      other species, the structural differences exhibited by the proteomes provides a
      glimpse of innovative therapeutic paths to fight malaria. Blocking biosynthesis
      of UDP-GlcNAc in the parasites is another promising option to reduce Plasmodium
      life cycle.

PMID- 29187235
TI  - Urine cell-free microRNA as biomarkers for transitional cell carcinoma.
AB  - OBJECTIVE: MicroRNA (miRNA) are short nucleotide strands with a regulatory
      function in the cell. Several miRNAs have been shown to be useful as biomarkers
      for different neoplasms. The aim of this project was to assess whether levels of
      miRNA in cell free urine could be used as a biomarker in transitional cell
      carcinoma (TCC). RESULTS: cDNA libraries were produced based on small RNAs in
      urine samples of fourteen TCC patients and twenty healthy volunteers. Resulting
      reads were deep sequenced on Illumina HiSeq sequencer with the intent of
      characterizing cell free urine miRNA profiles. A statistically significant
      difference was found for a single miRNA; miR-210 was > sixfold higher in the TCC
      group compared to the control group. Furthermore, we were able to produce a
      diagnostic score by summing of standardized levels of overexpressed miRNA. This
      score was considerably higher in TCC patients with a sensitivity of 0.93,
      specificity of 0.76 and negative predictive value > 0.97.

PMID- 29187236
TI  - Obstruction in the third portion of the duodenum due to a diospyrobezoar: a case
      report.
AB  - BACKGROUND: Duodenal obstruction occurs mainly due to physical lesions such as
      duodenal ulcers or tumors. Obstruction due to bezoars is rare. We describe an
      extremely rare case of obstruction in the third portion of the duodenum caused by
      a diospyrobezoar 15 months after laparoscopic distal gastrectomy for early
      gastric cancer. CASE PRESENTATION: A 73-year-old man who underwent laparoscopic
      distal gastrectomy for early gastric cancer 15 months before admission
      experienced abdominal distension and occasional vomiting. The symptoms worsened
      and ingestion became difficult; therefore, he was admitted to our department.
      Computed tomography (CT) performed on admission revealed a solid mass in the
      third portion of the duodenum and dilatation of the oral side of the duodenum and
      remnant stomach. Esophagogastroduodenoscopy (EGD) revealed a bezoar deep in the
      third portion of the duodenum. We could neither remove nor crush the bezoar. At
      midnight on the day of EGD, he experienced sudden abdominal pain. Repeat CT
      revealed that the bezoar had vanished from the duodenum and was observed in the
      ileum. Moreover, small bowel dilatation was observed on the oral side of the
      bezoar. Although CT showed neither free air nor ascites, laboratory data showed
      the increase of leukocyte (8400/MUL) and C-reactive protein (18.1 mg/dL), and
      abdominal pain was severe. Emergency surgery was performed because conservative
      treatment was considered ineffective. We tried advancing the bezoar into the
      colon, but the ileum was too narrow; therefore, we incised the ileum and removed
      the bezoar. The bezoar was ocher, elastic, and hard, and its cross-section was
      uniform and orange. The postsurgical interview revealed that the patient loved
      eating Japanese persimmons (Diospyros kaki); therefore, he was diagnosed with a
      diospyrobezoar. His postoperative progress was good and without complications. He
      left the hospital 10 days after surgery. EGD performed 4 weeks after surgery
      revealed no abnormal duodenal findings. CONCLUSIONS: We describe a rare case of
      obstruction in the third portion of the duodenum caused by a diospyrobezoar 15
      months after laparoscopic distal gastrectomy with Billroth I reconstruction for
      early gastric cancer.

PMID- 29187238
TI  - EuroTau: towing scientists to tau without tautology.

PMID- 29187237
TI  - "It wasn't as bad as I thought it would be": a qualitative study of early stage
      non-small cell lung cancer patients after treatment.
AB  - OBJECTIVE: While surgical resection is recommended for most patients with early
      stage lung cancer, stereotactic body radiotherapy (SBRT) is being increasingly
      utilized. Provider-patient communication regarding risks/benefits of each
      approach may be a modifiable factor leading to improved patient-centered
      outcomes. Our objective was to determine a framework and recommended strategies
      on how to best communicate with patients with early stage non-small cell lung
      cancer (NSCLC) in the post-treatment setting. We qualitatively evaluated the
      experiences of 11 patients with early clinical stage NSCLC after treatment, with
      a focus on treatment experience, knowledge obtained, communication, and
      recommendations. We used conventional content analysis and a patient-centered
      communication theoretical model to guide our understanding. RESULTS: Five
      patients received surgery and six received SBRT. Both treatments were generally
      well-tolerated. Few participants reported communication deficits around receiving
      follow-up information, although several had remaining questions about their
      treatment outcome (mainly those who underwent SBRT). They described feeling
      anxious regarding their first surveillance CT scan and clinician visit. Overall,
      participants remained satisfied with care because of implicit trust in their
      clinicians rather than explicit communication. Communication gaps remain but may
      be addressed by a trusting relationship with the clinician. Patients recommend
      clinicians give thorough explanations and personalize when possible.

PMID- 29187239
TI  - A model of population dynamics of TB in a prison system and application to South
      Africa.
AB  - BACKGROUND: Tuberculosis (TB) continues to spread in South African prisons in
      particular, as prisons are over-capacitated and have poor ventilation. The
      awaiting trial detainees are not screened on admission and are at high risk of
      getting infected with TB. RESULTS: We propose a compartmental model to describe
      the population dynamics of TB disease in prisons. Our model considers the inflow
      of susceptible, exposed and TB infectives into the prison population. Removal of
      individuals out of the prison population can be either by death or by being
      released from prison, as compared to a general population in which removal is
      only by death. We describe conditions, including non-inflow of infectives into
      the prison, which will ensure that TB can be eradicated from the prison
      population. The model is calibrated for the South African prison system, by using
      data in existing literature. The model can be used to make quantitative
      projections of TB prevalence and to measure the effect of interventions.
      Illustrative simulations in this regard are presented. The model can be used for
      other prison populations too, if data is available to calculate the model
      parameters. CONCLUSIONS: Various simulations generated with our model serve to
      illustrate how it can be utilized in making future projections of the levels of
      prevalence of TB, and to quantify the effect of interventions such as screening,
      treatment or reduction of transmission parameter values through improved living
      conditions for inmates. This makes it particularly useful as there are various
      targets set by the World Health Organization and by governments, for reduction of
      TB prevalence and ultimately its eradication. Towards eradication of TB from a
      prison system, the theorem on global stability of the disease-free state is a
      useful indicator.

PMID- 29187240
TI  - Effect of genetic ancestry to the risk of susceptibility to gastric cancer in a
      mixed population of the Brazilian Amazon.
AB  - BACKGROUND: Global literature describes differences in the incidence of gastric
      cancer among populations. For instance, Europeans have lower incidence rates of
      gastric cancer in relation to Latin and Asian populations, particularly Korean
      and Japanese populations. However, only a few studies have been able to verify
      the occurrence of gastric cancer in admixed populations with high interethnic
      degree mix, such as the Brazilian Amazon region. RESULTS: We observed an increase
      in European ancestry in the control group compared to the case group (47% vs.
      41%). Using increments of 10%, compared to categorical distribution of European
      ancestry in the sample, we found a difference in the contribution between cases
      and controls (p = 0.03). Multiple logistic regression was performed to determine
      the influence of European ancestry in susceptibility to gastric cancer in the
      sample. According to the adopted model, for each 10% increase in European
      ancestry, there is a 20% decrease chance of developing gastric cancer (P =
      0.0121; OR = 0.81; 95% CI 0.54-0.83). CONCLUSION: Overall, the results suggest
      that a greater contribution of European ancestry can be a protective factor for
      the development of gastric cancer in the studied Amazon population. It can help
      to establish protocols able to predict susceptibility to gastric cancer in
      admixed populations.

PMID- 29187241
TI  - Profile of red blood cell morphologies and causes of anaemia among pregnant women
      at first clinic visit in the mount Cameroon area: a prospective cross sectional
      study.
AB  - OBJECTIVE: Anaemia is a serious problem in pregnancy in malaria-endemic
      countries. This study investigated red cell morphologies and possible causes of
      anaemia among pregnant women at first clinic visit. Venous blood samples from
      consented women were used to determine haemoglobin (Hb) levels, mean corpuscular
      volume (MCV) and mean corpuscular haemoglobin (MCH) using an automated
      haematology analyzer. Malaria parasitaemia was diagnosed by microscopy.
      Definitions were as follows: anaemia (Hb < 11.0 g/dl), microcytosis (MCV < 78
      fl), macrocytosis (MCV > 101 fl), hypochromasia (MCH < 27 pg), microcytic
      hypochromia or normocytic hypochromia with anaemia [iron deficiency anaemia
      (IDA)], normocytic normochromia with anaemia in the absence of malaria
      parasitaemia (physiological anaemia of pregnancy). RESULTS: Of the 279 pregnant
      women enrolled, 57% had anaemia. Malaria parasitaemia was associated with 23.3%
      of anaemic cases while 76.7% were non-malaria related. The distribution of red
      cell alterations was as follows: hypochromasia (32.6%), microcytosis (14.7%) and
      macrocytosis (1.1%). The co-occurrence of malaria parasitaemia, iron deficiency
      and anaemia was seen in 23.3% of the women, iron deficiency anaemia only occurred
      in 35.9% while physiological anaemia of pregnancy was 40.9%. Iron deficiency and
      physiological anaemia of pregnancy contribute to a greater proportion of anaemia
      in the study area.

PMID- 29187242
TI  - Statistical analysis plan for the EuroHYP-1 trial: European multicentre,
      randomised, phase III clinical trial of the therapeutic hypothermia plus best
      medical treatment versus best medical treatment alone for acute ischaemic stroke.
AB  - BACKGROUND: Cooling may reduce infarct size and improve neurological outcomes in
      patients with ischaemic stroke. In phase II trials, cooling awake patients with
      ischaemic stroke has been shown to be feasible and safe, but the effects in
      functional outcomes has not yet been investigated in an adequately sized
      randomised clinical trial. METHODS/DESIGN: The EuroHYP-1 trial is a
      multinational, randomised, superiority phase III clinical trial with masked
      outcome assessment testing the benefits and harms of therapeutic cooling in awake
      adult patients with acute ischaemic stroke. The outcomes dealt with here include
      the primary outcome the Rankin score (mRS) at day 91 +/-14 days after
      randomisation. The secondary and exploratory outcomes at day 91 +/-14 days unless
      otherwise stated encompassing: (1) death or dependency, defined as mRS score > 2;
      (2) death; (3) National Institutes of Health Stroke Score; (4) brain infarct size
      at 48 +/-24 hours; (5) EQ-5D-5 L score, and (6) WHODAS 2.0 score. Other outcomes
      are: the primary safety outcome serious adverse events; and the incremental cost
      effectiveness, and cost utility ratios. The analysis sets include (1) the
      intention-to-treat population, and (2) the per protocol population. The sample
      size is estimated to 800 patients (5% type 1 and 20% type 2 errors). All analyses
      are adjusted for the protocol-specified stratification variables (nationality of
      centre), and the minimisation variables. In the analysis, we use ordinal
      regression (the primary outcome), logistic regression (binary outcomes), general
      linear model (continuous outcomes), and the Poisson or negative binomial model
      (rate outcomes). DISCUSSION: Major adjustments compared with the original
      statistical analysis plan encompass: (1) adjustment of analyses by nationality;
      (2) power calculations for the secondary outcomes; (3) to address the
      multiplicity problem using of a fixed-sequence testing procedure starting with
      the primary outcome followed by the secondary outcomes ordered according to
      falling power; (4) assignment of worst possible score to patients who are not
      alive at the planned date of measurement of the continuous scores; (5) improved
      imputations; (6) outline of a supplementary exploratory analysis of the
      temperature measurements and time to death; and (7) substantial reduction of
      sample size. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT01833312 . 4
      April 2013.

PMID- 29187244
TI  - Social media usage among health care providers.
AB  - OBJECTIVE: The objective of this study was to evaluate the use of social media
      among healthcare workers in an attempt to identify how it affects the quality of
      patient care. RESULTS: An anonymous survey of 35 questions was conducted in South
      Texas, on 366 healthcare workers. Of the 97% of people who reported owning
      electronic devices, 87.9% indicated that they used social media. These healthcare
      workers indicated that they spent approximately 1 h on social media every day.
      The healthcare workers below the age of 40 were more involved in social media
      compared to those above 40 (p < 0.05). The use of social media among physicians
      and nurses was noted to be identical (88% for each group), and both groups
      encouraged their patients to research their clinical conditions on social media
      (p < 0.05). A higher number of physicians reported awareness of a social media
      policy in their hospital compared to nurses (p < 0.05). However, a large
      proportion of healthcare workers (40%) were unaware of their workplace policy,
      which could potentially cause a privacy breach of confidential medical
      information. Further studies are required to evaluate specific effects of these
      findings on the quality of patient care.

PMID- 29187243
TI  - Doxycycline induces dysbiosis in female C57BL/6NCrl mice.
AB  - OBJECTIVE: This study aims to demonstrate the effect of oral doxycycline on fecal
      microbiota of mice. Doxycycline is a common effector for control of gene
      expression using the tet-inducible system in transgenic mice. The effect of oral
      doxycycline on murine gut microbiota has not been reported. We evaluated the
      effect of doxycycline treatment by sequencing the V4 hypervariable region of the
      16S rRNA gene from fecal samples collected during a 4 week course of treatment at
      a dose of 2 mg/ml in the drinking water. RESULTS: The fecal microbiota of treated
      animals were distinct from control animals; the decreased richness and diversity
      were characterized primarily by Bacteroides sp. enrichment. These effects
      persisted when the treatment was temporarily discontinued for 1 week. These data
      suggest that doxycycline treatment can induce significant dysbiosis, and its
      effects should be considered when used in animal models that are or maybe
      sensitive to perturbation of the gut microbiota.

PMID- 29187245
TI  - D-beta-Hydroxybutyrate and melatonin for treatment of porcine hemorrhagic shock
      and injury: a melatonin dose-ranging study.
AB  - OBJECTIVE: Treatment with a combination of D-beta-hydroxybutyrate (BHB) and
      melatonin (M) improves survival in hemorrhagic shock models. Our objective was to
      find the most effective melatonin concentration in combination with 4 molar BHB
      (4 M BHB). Survival and markers of organ injury were analyzed in pigs exposed to
      pulmonary contusion, liver crush injury, and hemorrhagic shock and treated with
      lactated Ringer's solution; 4 M BHB/43 mM M; 4 M BHB/20 mM M; 4 M BHB/10 mM M; 4
      M BHB/4.3 mM M; or 4 M BHB/0.43 mM M. This work is an extension of a previously
      published research study. RESULTS: Survival was highest in pigs receiving 4 M
      BHB/43 mM M (13/14), followed by lactated Ringer's solution (11/16) and BHB/M
      with decreased melatonin concentrations (4 M BHB/20 mM M 3/6, 4 M BHB/10 mM M
      2/6, 4 M BHB/4.3 mM M 3/6, 4 M BHB/0.43 mM M 1/6, p = 0.011). High mortality was
      associated with increases in serum lactate, higher liver and muscle injury
      markers and decreases in PaO2:FiO2 ratios. Our study indicates that treatment
      with 4 M BHB and melatonin concentrations below 43 mM lack the survival benefit
      observed from 4 M BHB/43 mM melatonin in pigs experiencing hemorrhagic shock and
      polytrauma.

PMID- 29187246
TI  - Comparison of Bispectral IndexTM values during the flotation restricted
      environmental stimulation technique and results for stage I sleep: a prospective
      pilot investigation.
AB  - OBJECTIVE: To determine whether Bispectral IndexTM values obtained during
      flotation-restricted environment stimulation technique have a similar profile in
      a single observation compared to literature-derived results found during sleep
      and other relaxation-induction interventions. RESULTS: Bispectral IndexTM values
      were as follows: awake-state, 96.6; float session-1, 84.3; float session-2, 82.3;
      relaxation-induction, 82.8; stage I sleep, 86.0; stage II sleep, 66.2; and stages
      III-IV sleep, 45.1. Awake-state values differed from float session-1 (%difference
      12.7%; Cohen's d = 3.6) and float session-2 (%difference 14.8%; Cohen's d = 4.6).
      Relaxation-induction values were similar to float session-1 (%difference 1.8%;
      Cohen's d = 0.3) and float session-2 (%difference 0.5%; Cohen's d = 0.1). Stage I
      sleep values were similar to float session-1 (%difference 1.9%; Cohen's d = 0.4)
      and float session-2 (%difference 4.3%; Cohen's d = 1.0). Stage II sleep values
      differed from float session-1 (%difference 21.5%; Cohen's d = 4.3) and float
      session-2 (%difference 19.6%; Cohen's d = 4.0). Stages III-IV sleep values
      differed from float session-1 (%difference 46.5%; Cohen's d = 5.6) and float
      session-2 (%difference 45.2%; Cohen's d = 5.4). Bispectral IndexTM values during
      flotation were comparable to those found in stage I sleep and nadir values
      described with other relaxation-induction techniques.

PMID- 29187247
TI  - Improvement of renal function after human umbilical cord mesenchymal stem cell
      treatment on chronic renal failure and thoracic spinal cord entrapment: a case
      report.
AB  - BACKGROUND: Chronic renal failure is an important clinical problem with
      significant socioeconomic impact worldwide. Thoracic spinal cord entrapment
      induced by a metabolic yield deposit in patients with renal failure results in
      intrusion of nervous tissue and consequently loss of motor and sensory function.
      Human umbilical cord mesenchymal stem cells are immune naive and they are able to
      differentiate into other phenotypes, including the neural lineage. Over the past
      decade, advances in the field of regenerative medicine allowed development of
      cell therapies suitable for kidney repair. Mesenchymal stem cell studies in
      animal models of chronic renal failure have uncovered a unique potential of these
      cells for improving function and regenerating the damaged kidney. CASE
      PRESENTATION: We report a case of a 62-year-old ethnic Indonesian woman
      previously diagnosed as having thoracic spinal cord entrapment with paraplegic
      condition and chronic renal failure on hemodialysis. She had diabetes mellitus
      that affected her kidneys and had chronic renal failure for 2 years, with
      creatinine level of 11 mg/dl, and no urinating since then. She was treated with
      human umbilical cord mesenchymal stem cell implantation protocol. This protocol
      consists of implantation of 16 million human umbilical cord mesenchymal stem
      cells intrathecally and 16 million human umbilical cord mesenchymal stem cells
      intravenously. Three weeks after first intrathecal and intravenous implantation
      she could move her toes and her kidney improved. Her creatinine level decreased
      to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is
      2 mg/dl with normal urinating. CONCLUSIONS: Human umbilical cord mesenchymal stem
      cell implantations led to significant improvement for spinal cord entrapment and
      kidney failure. The major histocompatibility in allogeneic implantation is an
      important issue to be addressed in the future.

PMID- 29187248
TI  - Operational research within the national tuberculosis control programme in Benin.
AB  - OBJECTIVE: To document whether the placement of operational research (OR) fellows
      within disease control programmes in low and middle income countries leads to the
      implementation of operational research and improvements in policy and practice.
      RESULT: In 2012, an OR fellow was placed within the National TB Programme, Benin,
      to strengthen the implementation of operational research. From 2012 to 2015,
      eight OR projects were implemented, of which three contributed to changes in
      programme practice and five provided information which was not previously
      available from quarterly/annual reports. Two of these projects-one on the burden
      and treatment outcomes of childhood TB and one on tracing patients who had
      discontinued treatment-are discussed in more detail. OR should be strongly
      encouraged within national TB programme settings and an OR fellow facilitates
      this process.

PMID- 29187249
TI  - Interventions to increase adherence in patients taking immunosuppressive drugs
      after kidney transplantation: a systematic review of controlled trials.
AB  - BACKGROUND: Immunosuppressive drugs have to be taken through the whole duration
      of kidney transplant survival to avoid rejection. Low adherence can increase the
      risk of allograft rejection. The objective was to evaluate the effectiveness of
      adherence-enhancing interventions (AEI) in kidney transplantation recipients
      taking immunosuppressive drugs. METHODS: A search was performed in Medline,
      Embase, CINAHL, and PsycINFO. The search was performed in May 2016. We included
      comparative studies on AEI for kidney transplant recipients taking
      immunosuppressive drugs. The primary outcome was medication adherence. All
      identified articles were screened according to the predefined inclusion criteria.
      The risk of bias was assessed with the Cochrane risk of bias tool. Study
      selection and risk of bias assessment were performed by two reviewers
      independently. Data were extracted in standardized tables. Data extraction was
      verified by a second reviewer. All discrepancies were resolved through
      discussion. Data were synthesized in a structured narrative way. There is no
      registered or published protocol for this systematic review. RESULTS: We
      identified 12 studies. The number of participants ranged from 24 to 1830. Nine
      studies included adults, two children, and one adults and children. Risk of bias
      was high. The main reasons for high risk of bias were inadequate allocation
      sequence (confounding) and that studies were not blinded. Eleven studies
      evaluated AEI consisting of educational and/or behavioral components. All these
      studies showed an effect direction in favor of the intervention. Intervention
      effect was only moderate. Most adherence measures in studies on educational and
      behavioral interventions showed statistically significant differences. Studies
      that combined educational and behavioral intervention components showed larger
      effects. All studies that were statistically significant were multimodal. Studies
      that included an individualized component and more intensive interventions showed
      larger effects. One study evaluated a reminder system. Effect size was not
      reported. This study showed no statistical significant difference (p > 0.05).
      CONCLUSION: Educational and behavioral AEI can increase adherence. In particular,
      multimodal and individualized interventions seem promising. However, because of
      the small effect, the high risk of bias, and the invalidity of adherence
      measures, the actual benefit of adherence interventions for an unselected patient
      population (i.e., including also adherent patients) seems limited. No conclusion
      is possible for interventions combining adherence-enhancing components that
      address intentional (behavioral) as well as unintentional adherence (reminder).

PMID- 29187250
TI  - Polymorphism rs13334190 in zinc finger protein 469 (ZNF469) is not a risk factor
      for keratoconus in a Saudi cohort.
AB  - OBJECTIVE: Polymorphism rs13334190 in the zinc finger protein 469 gene has been
      suggested to predispose toward a "thin" cornea, which then becomes keratoconic or
      is directly pathogenic. Thus, we genotyped polymorphism rs13334190 in 127
      unrelated keratoconus cases and 168 control subjects from Saudi Arabia using Taq
      Man(r) assay. RESULTS: The genotype frequency distribution did not deviate
      significantly from the Hardy-Weinberg equilibrium (p > 0.05). Overall, both the
      genotype and allele frequencies were not significantly different between cases
      and controls. A minor allele frequency of 0.068 was comparable to the aggregate
      rates ranging from 0.060 to 0.086 observed in other populations. Binary logistic
      regression analysis was performed to ascertain the effects of age, gender and
      genotype on the likelihood of having keratoconus. The analysis indicated that
      increased age was statistically significant (p = 0.000) and that females have a
      2.19-fold increased risk (p = 0.018) of developing keratoconus. The genotype
      frequencies did not differ between the sporadic or familial keratoconus cases.
      Polymorphism rs13334190 is not an independent risk factor for keratoconus in the
      Saudi cohort.

PMID- 29187251
TI  - Experiencing physical warmth affects implicit attitudes and altruistic behavior
      toward outgroup in females.
AB  - OBJECTIVE: Experiencing physical warmth has been demonstrated to influence
      interpersonal warmth. However, the effects of this metaphorical link in an
      intergroup context is not clear. The current study aimed to investigate the
      effect of physical warmth on implicit attitudes and behavior toward outgroup
      members in a Japanese-Chinese intergroup context. After touching either a warm or
      cold cup for 3 min, the Japanese participants were required to complete the
      single-target implicit association test, which aimed to measure their implicit
      attitudes toward imagined Chinese people, and to express their willingness to
      participate in the experiments of a Chinese individual whom they interacted
      directly without compensation, aiming to measure their prosocial behavior toward
      a real outgroup member. RESULTS: The results demonstrated that female
      participants who touched the warm (vs. cold) cup showed more positive attitudes
      and helping behavior toward the Chinese individual. Furthermore, the correlation
      between those attitudes and helping behaviors supports the effects of enhanced
      implicit attitudes and further suggests that experiencing physical warmth could
      increase prosocial response to outgroup members in real interactions. However,
      the male participants showed a reversed, but not statistically significant,
      effect of physical warmth on the implicit attitude.

PMID- 29187254
TI  - Acute disseminated melioidosis giving rise to pneumonia and renal abscesses
      complicated with thrombotic thrombocytopenic purpura in a post partum woman: a
      case report.
AB  - BACKGROUND: Melioidosis is an established endemic infection in Sri Lanka, caused
      by Burkholderia pseudomallei, a gram negative bacterium distributed in
      saprophytes in soil and surface water. Main mode of transmission is via
      percutaneous inoculation. Pneumonia is the most common presentation in acute
      disease. CASE PRESENTATION: We report a 33 year old previously healthy Sinhalese
      female with an occupational exposure to surface water in paddy fields, who was on
      postpartum day 6 following an uncomplicated pregnancy and delivery via an
      elective caesarian section. She presented with a 1 day history of breathlessness,
      preceded by a brief episode of fever. She had occasional right side coarse
      crackles and pitting oedema of both lower limbs. Shortly after admission, she
      developed type one respiratory failure needing invasive mechanical ventilation.
      Initial chest x-ray revealed slight obliteration of right medial diaphragmatic
      border while echocardiogram revealed moderate pulmonary hypertension. Computed
      tomography pulmonary angiogram excluded a pulmonary embolism, but revealed
      bilateral multi-lobar consolidation. Abdominal computed tomography demonstrated
      bilateral pyelonephritis with renal abscesses. As initial cultures were
      inconclusive, melioidosis antibody levels were done due to high degree of
      suspicion, which was found to be positive with a titer of 1:2560. A diagnosis of
      melioidosis was made based on the suggestive clinical picture, exposure history
      and the highly positive antibody level. She developed left side focal seizures
      together with thrombocytopenia and microangiopathic haemolytic anemia, suggestive
      of thrombotic thrombocytopenic purpura. Magnetic resonance imaging of brain was
      negative for cerebral abscesses but revealed extensive minute haemorrhagic foci
      throughout the cerebrum. Thus, the final diagnosis was acute melioidosis causing
      pneumonia and renal abscesses, complicated with thrombotic thrombocytopenic
      purpura and sepsis. She demonstrated dramatic response to high dose meropenem and
      co-trimoxazole along with plasmapheresis. Four weeks after treatment, the
      antibody titer came down to 1:320. Melioidosis antibody was absent in the baby.
      CONCLUSIONS: This case was challenging as it was an atypical presentation of
      melioidosis during postpartum leading to a diagnostic conundrum. This highlights
      the need to look into the effect of pregnancy and postpartum as added risk
      factors. High index of suspicion is necessary to avoid diagnostic delays.

PMID- 29187252
TI  - Atypical, non-standard functions of the microtubule associated Tau protein.
AB  - Since the discovery of the microtubule-associated protein Tau (MAPT) over 40
      years ago, most studies have focused on Tau's role in microtubule stability and
      regulation, as well as on the neuropathological consequences of Tau
      hyperphosphorylation and aggregation in Alzheimer's disease (AD) brains. In
      recent years, however, research efforts identified new interaction partners and
      different sub-cellular localizations for Tau suggesting additional roles beyond
      its standard function as microtubule regulating protein. Moreover, despite the
      increasing research focus on AD over the last decades, Tau was only recently
      considered as a promising therapeutic target for the treatment and prevention of
      AD as well as for neurological pathologies beyond AD e.g. epilepsy,
      excitotoxicity, and environmental stress. This review will focus on atypical, non
      standard roles of Tau on neuronal function and dysfunction in AD and other
      neurological pathologies providing novel insights about neuroplastic and
      neuropathological implications of Tau in both the central and the peripheral
      nervous system.

PMID- 29187253
TI  - Diffusion tensor imaging and tractography of the sciatic and femoral nerves in
      healthy volunteers at 3T.
AB  - BACKGROUND: The aim was to clarify the normal fractional anisotropy (FA) and
      apparent diffusion coefficient (ADC) values of the sciatic and femoral nerves at
      the level of the hip joint and to visualize the neural tracts with diffusion
      tensor imaging (DTI). METHODS: Twenty-four healthy volunteers (12 men and 12
      women, age 20-29 years) underwent DTI for visualization with tractography and
      quantification of FA and ADC values on a 3 Tesla MRI (b value = 800 s/mm2, motion
      probing gradient, 11 directions, time to repeat/echo time = 9000/72.6 ms, axial
      slice orientation, slice thickness = 3.0 mm with no inter-slice gap, field of
      view = 320 * 320 mm, 96 * 192 matrix, 75 slices, number of acquisitions = 4).
      Regions of interest in the sciatic nerve were defined at the femoral head, the S1
      root, and the midpoint levels. The femoral nerve was evaluated at 3-4 cm proximal
      to the femoral head level. RESULTS: The tractography of the sciatic and femoral
      nerves were visualized in all participants. The mean FA values of the sciatic
      nerve were increased distally from the S1 root level, through the midpoint, and
      to the femoral head level (0.314, 0.446, 0.567, p = 0.001, respectively). The
      mean FA values of the femoral nerve were 0.565. The mean ADC values of the
      sciatic nerves were significantly lower in the S1 root level than in the midpoint
      and the femoral head level (1.481, 1.602, 1.591 * 10-3 * 10-3 mm2/s, p = 0.001,
      respectively). The ADC values of the femoral nerve were 1.439 * 10-3 mm2/s. FA
      and ADC values showed moderate to substantial inter- and intra-observer
      reliability without significant differences in gender or laterality. CONCLUSION:
      Visualization and quantification of the sciatic and femoral nerves simultaneously
      around the hip joint were achieved in healthy young volunteers with DTI. Clinical
      application of DTI is expected to contribute to hip pain research.

PMID- 29187255
TI  - A novel loop-mediated isothermal amplification-based test for detecting Neospora
      caninum DNA.
AB  - BACKGROUND: Neospora caninum is a cyst-forming, coccidian parasite which is known
      to cause neurological disorders in dogs and abortion and neonatal mortality in
      cows and other livestock. This study reports the development of a loop-mediated
      isothermal amplification (LAMP) assay based on the Neospora caninum Nc-5 gene and
      compares its efficacy for detecting DNA to that of a semi-nested PCR test.
      RESULTS: Six primers were designed based on the Nc-5 repeat region of N. caninum.
      Specific LAMP primers led to successful amplification of N. caninum DNA at 63 
      degrees C in 30 min. The LAMP assay was highly specific (i.e. it did not reveal
      cross-reactivity with other parasite species) and had a low N. caninum plasmid
      DNA limit of detection (1 fg), which is ten times higher than that for the semi
      nested PCR. LAMP applicability was evaluated using a set of naturally-infected
      samples (59 from canine faeces and five from bovine abortions). Thirty-nine
      percent (25/64) of the naturally-infected samples were positive for N. caninum
      DNA by LAMP and 36% (23/64) by semi-nested PCR. However, the LAMP assay is much
      faster to perform than semi-nested PCR and provides results in 30 min.
      CONCLUSION: The optimized reaction conditions described in this study resulted in
      a sensitive, specific and rapid technique for detecting N. caninum DNA.
      Considering the advantages of LAMP for detecting N. caninum DNA, further assays
      aimed at testing its usefulness on a wider range of field samples are
      recommended.

PMID- 29187257
TI  - Urbanization, economic development and health: evidence from China's labor-force
      dynamic survey.
AB  - BACKGROUND: The frequent outbreak of environmental threats in China has resulted
      in increased criticism regarding the health effects of China's urbanization.
      Urbanization is a double-edged sword with regard to health in China. Although
      great efforts have been made to investigate the mechanisms through which
      urbanization influences health, the effect of both economic development and
      urbanization on health in China is still unclear, and how urbanization-health (or
      development-health) relationships vary among different income groups remain
      poorly understood. To bridge these gaps, the present study investigates the
      impact of both urbanization and economic development on individuals' self-rated
      health and its underlying mechanisms in China. METHODS: We use data from the
      national scale of the 2014 China Labor-force Dynamics Survey to analyze the
      impact of China's urbanization and economic development on health. A total of
      14,791 individuals were sampled from 401 neighborhoods within 124 prefecture
      level cities. Multilevel ordered logistic models were applied. RESULTS: Model
      results showed an inverted U-shaped relationship between individuals' self-rated
      health and urbanization rates (with a turning point of urbanization rate at
      42.0%) and a positive linear relationship between their self-rated health and
      economic development. Model results also suggested that the urbanization-health
      relationship was inverted U-shaped for high- and middle-income people (with a
      turning point of urbanization rate at 0.0% and 49.2%, respectively), and the
      development-health relationship was inverted U-shaped for high- and low-income
      people (with turning points of GDP per capita at 93,462 yuan and 71,333 yuan,
      respectively) and linear for middle-income people. CONCLUSION: The impact of
      urbanization and economic development on health in China is complicated. Careful
      assessments are needed to understand the health impact of China's rapid
      urbanization. Social and environmental problems arising from rapid urbanization
      and economic growth should be addressed. Equitable provision of health services
      are needed to improve low-income groups' health in highly urbanized cities.

PMID- 29187256
TI  - Astrocytes in mouse models of tauopathies acquire early deficits and lose
      neurosupportive functions.
AB  - Microtubule-associated protein tau aggregates constitute the characteristic
      neuropathological features of several neurodegenerative diseases grouped under
      the name of tauopathies. It is now clear that the process of tau aggregation is
      associated with neurodegeneration. Several transgenic tau mouse models have been
      developed where tau progressively aggregates, causing neuronal death. Previously
      we have shown that transplantation of astrocytes in P301S tau transgenic mice
      rescues cortical neuron death, implying that the endogenous astrocytes are
      deficient in survival support. We now show that the gliosis markers Glial
      fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100beta)
      are elevated in brains from P301S tau mice compared to control C57Bl/6 mice
      whereas the expression of proteins involved in glutamine/glutamate metabolism are
      reduced, pointing to a functional deficit. To test whether astrocytes from P301S
      mice are intrinsically deficient, we co-cultured astrocytes and neurons from
      control and P301S mice. Significantly more C57-derived and P301S-derived neurons
      survived when cells were cultured with C57-derived astrocytes or astrocyte
      conditioned medium (C57ACM) than with P301S-derived astrocytes or astrocyte
      conditioned medium (P301SACM), or ACM from P301L tau mice, where the transgene is
      also specifically expressed in neurons. The astrocytic alterations developed in
      mice during the first postnatal week of life. In addition, P301SACM significantly
      decreased presynaptic (synaptophysin, SNP) and postsynaptic (postsynaptic density
      protein 95, PSD95) protein expression in cortical neuron cultures whereas C57ACM
      enhanced these markers. Since thrombospondin 1 (TSP-1) is a major survival and
      synaptogenic factor, we examined whether TSP-1 is deficient in P301S mouse brains
      and ACM. Significantly less TSP-1 was expressed in the brains of P301S tau mice
      or produced by P301S-derived astrocytes, whereas supplementation of P301SACM with
      TSP-1 increased its neurosupportive capacity. Our results demonstrate that P301S
      derived astrocytes acquire an early functional deficiency that may explain in
      part the loss of cortical neurons in the P301S tau mice.

PMID- 29187258
TI  - Medical educators' perception of communication training with simulated patients:
      an explorative study approach.
AB  - OBJECTIVE: Medical students' perceptions of the use of simulated patients (SP) in
      communication training in medicine have been studied intensively, but insights
      about faculty perception of this type of simulation training remain rare. This
      study aimed to assess medical educators' perception of the relevancy of SP
      communication training, as well as its closeness to reality. Medical educators
      were surveyed by standardized questionnaire and open-ended questions. The
      questionnaire allowed educators to rate several aspects of the training such as
      its closeness to reality and relevancy to real-life physician-patient
      interaction. RESULTS: Educators' perception of relevance and realism of SP
      training increases with teaching experience. This appears to be influenced by
      factors such as internal or external status of the educator, personal experience
      with communication training during medical studies, as well as medical field
      taught. Communication training with SP is valued highly by medical educators
      mainly because of its versatility and broad spectrum of applicability. The wide
      range of application of SP in medical education seems most evident to senior
      educators because of their increased amount of experience with physician-patient
      interaction, whereas junior educators appear often hindered by the aspect of
      simulation caused by the thought that the patients are "merely" actors.

PMID- 29187260
TI  - Histological changes of the meniscus following an osteochondral lesion.
AB  - In the last few years, different tissue engineering strategies have been
      developed for the repair of osteochondral lesions. When the osteochondral
      scaffold is implanted on the femoral condyle, the meniscus might be affected by
      the implant and might undergo a progressive degeneration. The aim of our study is
      to analyze the morphological changes of the meniscus following an osteochondral
      lesion and the implant of a biphasic scaffold. A critical osteochondral defect
      was generated in the medial femoral condyle of mature sheep. Three defects were
      left untreated, the remaining lesions were divided into three groups and treated
      with a biphasic substituted formed by collagen type I and Wollastonite or
      Wollastonite/Hydroxyapatite. Animals were sacrificed after 6 months and menisci
      were isolated and analyzed by arthro-CT, macroscopic evaluation and histology.
      The results demonstrated that the osteochondral lesion negatively affects
      meniscus morphology and that the osteochondral substitute only partially
      mitigates the meniscus degeneration.

PMID- 29187259
TI  - Impact of IQ on the diagnostic yield of chromosomal microarray in a community
      sample of adults with schizophrenia.
AB  - BACKGROUND: Schizophrenia is a severe psychiatric disorder associated with IQ
      deficits. Rare copy number variations (CNVs) have been established to play an
      important role in the etiology of schizophrenia. Several of the large rare CNVs
      associated with schizophrenia have been shown to negatively affect IQ in
      population-based controls where no major neuropsychiatric disorder is reported.
      The aim of this study was to examine the diagnostic yield of microarray testing
      and the functional impact of genome-wide rare CNVs in a community ascertained
      cohort of adults with schizophrenia and low (< 85) or average (>= 85) IQ.
      METHODS: We recruited 546 adults of European ancestry with schizophrenia from six
      community psychiatric clinics in Canada. Each individual was assigned to the low
      or average IQ group based on standardized tests and/or educational attainment. We
      used rigorous methods to detect genome-wide rare CNVs from high-resolution
      microarray data. We compared the burden of rare CNVs classified as pathogenic or
      as a variant of unknown significance (VUS) between each of the IQ groups and the
      genome-wide burden and functional impact of rare CNVs after excluding individuals
      with a pathogenic CNV. RESULTS: There were 39/546 (7.1%; 95% confidence interval
      [CI] = 5.2-9.7%) schizophrenia participants with at least one pathogenic CNV
      detected, significantly more of whom were from the low IQ group (odds ratio [OR]
      = 5.01 [2.28-11.03], p = 0.0001). Secondary analyses revealed that individuals
      with schizophrenia and average IQ had the lowest yield of pathogenic CNVs (n =
      9/325; 2.8%), followed by those with borderline intellectual functioning (n =
      9/130; 6.9%), non-verbal learning disability (n = 6/29; 20.7%), and co-morbid
      intellectual disability (n = 15/62; 24.2%). There was no significant difference
      in the burden of rare CNVs classified as a VUS between any of the IQ subgroups.
      There was a significantly (p=0.002) increased burden of rare genic duplications
      in individuals with schizophrenia and low IQ that persisted after excluding
      individuals with a pathogenic CNV. CONCLUSIONS: Using high-resolution microarrays
      we were able to demonstrate for the first time that the burden of pathogenic CNVs
      in schizophrenia differs significantly between IQ subgroups. The results of this
      study have implications for clinical practice and may help inform future rare
      variant studies of schizophrenia using next-generation sequencing technologies.

PMID- 29187262
TI  - Novel circulating microRNAs expression profile in colon cancer: a pilot study.
AB  - PURPOSE: To identify the expression profile of novel microRNAs (miRNAs) in colon
      cancer and evaluate their clinical applicability. METHODS: Differences in the
      expression of serum miRNAs in patients with colon cancer and healthy controls
      were identified using miRNA microarrays. Differentially expressed miRNAs were
      verified via real-time polymerase chain reaction (PCR) using sera from 50
      patients with colon cancer and 44 healthy controls. These miRNAs were also
      verified in a double-blind validation experiment using sera from 30 patients with
      colon cancer, 30 patients with colonic polyps, and 30 healthy controls. RESULTS:
      Microarray hybridization revealed that 87 miRNAs were differentially expressed
      between the sera of patients with colon cancer and healthy controls. Among these
      miRNAs, 39 miRNAs were up-regulated, whereas 48 miRNAs were down-regulated.
      Verification of the expression of these miRNAs using real-time PCR revealed that
      the expression levels of miR-31, miR-141, miR-224-3p, miR-576-5p, and miR-4669
      were significantly different between patients with colon cancer and healthy
      controls. Using these five miRNAs to construct a miRNA expression profile (or
      miRNA panel) will facilitate more effective diagnosis of colon cancer.
      CONCLUSION: Clinical analysis of miR-31, miR-141, miR-224-3p, miR-576-5p, and miR
      4669 expression in patients with colon cancer may facilitate the diagnosis of
      colon cancer.

PMID- 29187264
TI  - Quantitation and Confirmation of Chloramphenicol, Florfenicol, and Nitrofuran
      Metabolites in Honey Using LC-MS/MS.
AB  - This paper describes a rapid and robust method utilizing a single liquid-liquid
      extraction for the quantitation and confirmation of chloramphenicol, florfenicol,
      and nitrofuran metabolites in honey. This methodology combines two previous
      extraction methods into a single extraction procedure and utilizes matrix-matched
      calibration standards and stable isotopically labeled standards to improve
      quantitation. The combined extraction procedure reduces the average extraction
      time by >50% when compared with previously used procedures. The drug residues
      were determined using two separate LC-tandem MS conditions. Validation of all the
      analytes was performed, with average quantitation ranging from 92 to 105% for all
      analytes and the RSDs for all analytes being <=12%.

PMID- 29187265
TI  - Development and Evaluation of an Enzyme-Linked Immunosorbent Assay Using a
      Nonpoisonous Extraction System for the Determination of Crustacean Protein in
      Processed Foods.
AB  - Crustacean proteins are food allergens that cause severe allergic reactions in
      patients with food allergies; therefore, the identification of crustaceans such
      as shrimp, crab, and lobster as ingredients in processed food products is
      mandatory in Japan. We previously developed and validated an ELISA method coupled
      with an extraction process using the surfactant sodium dodecyl sulfate and the
      reductant 2-mercaptoethanol (2-ME) to quantify crustacean protein. However, 2-ME
      was designated as poisonous in Japan in 2008. Therefore, in this study, we
      developed and evaluated an ELISA method for detecting and quantifying crustacean
      protein that uses sodium sulfite (Na2SO3) in place of 2-ME for extraction. The
      proposed ELISA method showed high sensitivity, with an LOQ of 0.66 MUg protein/g
      food sample. Furthermore, the proposed method showed high specificity for the
      Decapoda order within the subphylum Crustacea, with recoveries ranging from 83.8
      to 100.8% for model processed foods, as well as high reproducibility (intra- and
      interassay CVs of <=8.2%) and high correlation with our previously validated
      ELISA method for processed foods (correlation coefficient of 0.996). The proposed
      ELISA method does not require the use of poisonous reagents, provides acceptable
      accuracy, and is useful for the routine monitoring of food products.

PMID- 29187263
TI  - Outbreak Response and Incident Management: SHEA Guidance and Resources for
      Healthcare Epidemiologists in United States Acute-Care Hospitals.

PMID- 29187266
TI  - Guidance for compassionate restraint of small children to prevent injuries with
      epinephrine autoinjectors.
AB  - BACKGROUND: Without securing a child properly, injuries can happen with the use
      of pediatric epinephrine autoinjectors (EAI), and lacerations and embedded
      needles have been reported. Health care providers should ensure that instruction
      is provided to parents on how to hold a child during an injection with an EAI.
      OBJECTIVE: To demonstrate the compassionate restraint of small children during an
      allergic emergency to ensure the safe use of an EAI. METHODS: A patient was used
      to illustrate a compassionate restraint technique during a mock injection with an
      EAI. RESULTS: One possible technique was illustrated here to reinforce the need
      for complete, yet compassionate restraint of small children during the use of an
      EAI. The exact position intended to be used by parents or caregivers will need to
      be practiced with their children to ensure a safe injection in the event of an
      allergic emergency. CONCLUSION: Reinforcement of proper EAI use and visual
      guidance that illustrate compassionate restraint can potentially prevent EAI
      related injuries.

PMID- 29187261
TI  - Initial nutritional management during noninvasive ventilation and outcomes: a
      retrospective cohort study.
AB  - BACKGROUND: Patients starting noninvasive ventilation (NIV) to treat acute
      respiratory failure are often unable to eat and therefore remain in the fasting
      state or receive nutritional support. Maintaining a good nutritional status has
      been reported to improve patient outcomes. In the present study, our primary
      objective was to describe the nutritional management of patients starting first
      line NIV, and our secondary objectives were to assess potential associations
      between nutritional management and outcomes. METHODS: Observational retrospective
      cohort study of a prospective database fed by 20 French intensive care units.
      Adult medical patients receiving NIV for more than 2 consecutive days were
      included and divided into four groups on the basis of nutritional support
      received during the first 2 days of NIV: no nutrition, enteral nutrition,
      parenteral nutrition only, and oral nutrition only. RESULTS: Of the 16,594
      patients admitted during the study period, 1075 met the inclusion criteria; of
      these, 622 (57.9%) received no nutrition, 28 (2.6%) received enteral nutrition,
      74 (6.9%) received parenteral nutrition only, and 351 (32.7%) received oral
      nutrition only. After adjustment for confounders, enteral nutrition (vs. no
      nutrition) was associated with higher 28-day mortality (adjusted HR, 2.3; 95% CI,
      1.2-4.4) and invasive mechanical ventilation needs (adjusted HR, 2.1; 95% CI, 1.1
      4.2), as well as with fewer ventilator-free days by day 28 (adjusted relative
      risk, 0.7; 95% CI, 0.5-0.9). CONCLUSIONS: Nearly three-fifths of patients
      receiving NIV fasted for the first 2 days. Lack of feeding or underfeeding was
      not associated with mortality. The optimal route of nutrition for these patients
      needs to be investigated.

PMID- 29187267
TI  - Long Noncoding RNA (lncRNA) HOTAIR Affects Tumorigenesis and Metastasis of Non
      Small Cell Lung Cancer by Upregulating miR-613.
AB  - Non-small cell lung cancer (NSCLC) is one of the most deadly cancers with poor
      prognosis. Recent findings suggested that the lncRNA HOTAIR played an important
      role in tumorigenesis and metastasis. In the present study, HOTAIR was highly
      expressed in NSCLC tumor tissues and cell lines (H1299, H23, H292, and A549).
      Downregulation of HOTAIR suppressed cell proliferation and invasion, while it
      promoted apoptosis of NSCLC cells. The targeting relationship between HOTAIR and
      miR-613 was first revealed by bioinformatics prediction. miR-613 was found to be
      lowly expressed in NSCLC tumor tissues and cell lines. Knockdown of HOTAIR
      increased the expression of miR-613 significantly, and cotransfection with miR
      613 inhibitor reversed this increase, indicating that the expression of miR-613
      was negatively regulated by HOTAIR. The targeting relationship between HOTAIR and
      miR-613 was further confirmed through the luciferase report assay. Moreover, the
      cotransfection of HOTAIR shRNA and miR-613 inhibitor counteracted the tumor
      inhibition effects of HOTAIR shRNA through promoting cell proliferation and
      invasion while suppressing apoptosis in NSCLC cells, suggesting that the
      HOTAIR/miR-613 axis was involved in tumorigenesis and metastasis of NSCLC. In
      vivo experiments revealed that knockdown of HOTAIR decreased tumor growth and
      invasion and increased apoptosis and miR-613 expression. In conclusion, our study
      indicated that downregulation of HOTAIR suppressed tumorigenesis and metastasis
      of NSCLC via upregulating the expression of miR-613. The HOTAIR/miR-613 axis
      might provide a new potential therapeutic strategy for NSCLC treatment.

PMID- 29187269
TI  - Ophthalmic Paracoccidioidomycosis.

PMID- 29187270
TI  - Clara Southmayd Ludlow: Her Thirst for Knowledge was Positively Inspirational:
      Honoring a Female Giant in Tropical Medicine.

PMID- 29187271
TI  - 2017 Bailey K. Ashford, Donald Mackay, and Walter Reed Medal Recipients.

PMID- 29187272
TI  - Reproducibility of Diagnostic Criteria for Ventricular Neurocysticercosis.

PMID- 29187273
TI  - Reproducibility of Diagnostic Criteria for Ventricular Neurocysticercosis.

PMID- 29187274
TI  - The Impact of Ken Warren's Leadership of the Rockefeller Foundation's Great
      Neglected Diseases Program on the Future of Malaria Research.

PMID- 29187275
TI  - "The Way We Were" Ken Warren's Legacy and Modern Investments in Global Health.

PMID- 29187276
TI  - Brain Worms with Cerebrospinal Fluid Eosinophilia.

PMID- 29187277
TI  - Molecular Identification of Onchocerca spp. Larvae in Simulium damnosum sensu
      lato Collected in Northern Uganda.
AB  - Previous studies have demonstrated that the presence of larvae of other filarial
      species in Simulium damnosum sensu lato can distort estimates of transmission
      potential for Onchocerca volvulus in West Africa. However, studies conducted in
      foci of onchocerciasis in West Central Uganda indicated that larvae other than O.
      volvulus were not common in vectors collected there. Recent data collected in
      Northern Uganda revealed a striking discordance between estimates of the
      prevalence of flies carrying O. volvulus infective larvae obtained from molecular
      pool screening and dissection methods. To resolve this discrepancy, sequences
      from three mitochondrially encoded genes were analyzed from the larvae collected
      by dissection. All larvae analyzed were Onchocerca ochengi v. Siisa, a parasite
      of cattle, or Onchocerca ramachandrini, a parasite of warthogs. These results
      suggest that nonhuman parasite larvae are common in vectors in Northern Uganda,
      underscoring the necessity for molecular identification methods to accurately
      estimate O. volvulus transmission.

PMID- 29187278
TI  - Head Lice: An Under-Recognized Tropical Problem.

PMID- 29187280
TI  - Promoting and improving three Rs practice: the Korean guidelines.
AB  - Scientists planning research that involves the use of animals are required to
      examine the possibilities for replacement, reduction, or refinement (the Three
      Rs), and their protocol must be reviewed by the Institutional Animal Care and Use
      Committee. Good scientific practice involving appropriate search techniques on
      the available Three Rs resources is essential for both ethical and scientific
      reasons. Appropriate experimental design and statistical analysis techniques are
      particularly necessary for research involving the use of animals, because this
      can improve animal welfare and scientific outcomes, as well as saving animal
      lives. There are a number of resources to help researchers improve their search
      techniques, experimental design strategies, and their reporting of research
      involving the use of animals. However, there is little specific information or
      resources on the Three Rs alternatives that is readily available in the Korean
      language. This paper outlines the common errors made by submitting researchers
      that have been repeatedly observed during the ethical review of experimental
      protocols over the last ten years, and provides information on the Korean
      resources available to promote good scientific practice. This could help to
      bridge the gap between Korean scientists and animal welfare advocates assisting
      scientists to improve ethical considerations and conduct responsible research.
      [BMB Reports 2017; 50(12): 610-614].

PMID- 29187279
TI  - Upstream signalling of mTORC1 and its hyperactivation in type 2 diabetes (T2D).
AB  - Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell
      growth, proliferation, polarity, differentiation, development, and controls
      transitioning between anabolic and catabolic states of the cell. It collects
      almost all extracellular and intracellular signals from growth factors,
      nutrients, and maintains cellular homeostasis, and is involved in several
      pathological conditions including, neurodegeneration, Type 2 diabetes (T2D),
      obesity, and cancer. In this review, we summarize current knowledge of upstream
      signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which
      state, the role of telomere attrition is explained. We discuss if chronic
      inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation.
      In conclusion, we suggest the regulatory roles of telomerase (TERT) and
      hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The
      former inhibits mTORC1 under nutrientrich while the latter under starved
      condition. We provide an idea of TOS (TOR signaling) motifs that can be used for
      regulation of mTORC1. [BMB Reports 2017; 50(12): 601-609].

PMID- 29187282
TI  - Prevalence of negative frequency-dependent selection, revealed by incomplete
      selective sweeps in African populations of Drosophila melanogaster.
AB  - Positive selection on a new beneficial mutation generates a characteristic
      pattern of DNA sequence polymorphism when it reaches an intermediate allele
      frequency. On genome sequences of African Drosophila melanogaster, we detected
      such signatures of selection at 37 candidate loci and identified "sweeping
      haplotypes (SHs)" that are increasing or have increased rapidly in frequency due
      to hitchhiking. Based on geographic distribution of SH frequencies, we could
      infer whether selective sweeps occurred starting from de novo beneficial mutants
      under simple constant selective pressure. Single SHs were identified at more than
      half of loci. However, at many other loci, we observed multiple independent SHs,
      implying soft selective sweeps due to a high beneficial mutation rate or parallel
      evolution across space. Interestingly, SH frequencies were intermediate across
      multiple populations at about a quarter of the loci despite relatively low
      migration rates inferred between African populations. This invokes a certain form
      of frequency-dependent selection such as heterozygote advantage. At one locus, we
      observed a complex pattern of multiple independent that was compatible with
      recurrent frequency-dependent positive selection on new variants. In conclusion,
      genomic patterns of positive selection are very diverse, with equal contributions
      of hard and soft sweeps and a surprisingly large proportion of frequencydependent
      selection in D. melanogaster populations. [BMB Reports 2018; 51(1): 1-2].

PMID- 29187281
TI  - HCBP6 upregulates human SREBP1c expression by binding to C/EBPbeta-binding site
      in the SREBP1c promoter.
AB  - Sterol regulatory element-binding protein-1c (SREBP1c) plays an important role in
      triglyceride (TG) homeostasis. Although our previous study showed that hepatitis
      C virus core-binding protein 6 (HCBP6) regulates SREBP1c expression to maintain
      intracellular TG homeostasis, the mechanism underlying this regulation is
      unclear. In the present study, we found that HCBP6 increased intracellular TG
      levels by upregulating SREBP1c expression. HCBP6 increased SREBP1c transcription
      by directly binding to the SREBP1c promoter (at the -139- to +359-bp region).
      Moreover, we observed that HCBP6 interacted with C/EBPbeta-binding site in the
      SREBP1c promoter both in vitro and in vivo. These results indicate that HCBP6
      upregulates human SREBP1c expression by binding to the C/EBPbeta-binding site in
      the SREBP1c promoter. [BMB Reports 2018; 51(1): 33-38].

PMID- 29187283
TI  - New insight into transglutaminase 2 and link to neurodegenerative diseases.
AB  - Formation of toxic protein aggregates is a common feature and mainly contributes
      to the pathogenesis of neurodegenerative diseases (NDDs), which include
      amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and
      prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional
      enzyme, displaying four types of activity, such as transamidation, GTPase,
      protein disulfide isomerase, and protein kinase activities. Many studies
      demonstrated that the calcium-dependent transamidation activity of TG2 affects
      the formation of insoluble and toxic amyloid aggregates that mainly consisted of
      NDD-related proteins. So far, many important and NDD-related substrates of TG2
      have been identified, including amlyoid-beta, tau, alpha-synuclein, mutant
      huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein
      43. Recently, the formation of toxic inclusions mediated by several TG2
      substrates were efficiently inhibited by TG2 inhibitors. Therefore, the
      development of highly specific TG2 inhibitors would be an important tool in
      alleviating the progression of TG2-related brain disorders. In this review, the
      authors discuss recent advances in TG2 biochemistry, several mechanisms of
      molecular regulation and pleotropic signaling functions, and the presumed role of
      TG2 in the progression of many NDDs. [BMB Reports 2018; 51(1): 5-13].

PMID- 29187286
TI  - Inflammation of Actinic Keratosis During Panitumumab Therapy.

PMID- 29187284
TI  - JQ1, a BET inhibitor, controls TLR4-induced IL-10 production in regulatory B
      cells by BRD4-NF-kappaB axis.
AB  - Regulatory B cells, also well-known as IL-10-producing B cells, play a role in
      the suppression of inflammatory responses. However, the epigenetic modulation of
      regulatory B cells is largely unknown. Recent studies showed that the bromodomain
      and extra-terminal domain (BET) protein inhibitor JQ1 controls the expression of
      various genes involving cell proliferation and cell cycle. However, the role of
      BET proteins on development of regulatory B cells is not reported. In this study,
      JQ1 potently suppressed IL-10 expression and secretion in murine splenic and
      peritoneal B cells. While bromodomaincontaining protein 4 (BRD4) was associated
      with NF-kappaB on IL-10 promoter region by LPS stimulation, JQ1 interfered the
      interaction of BRD4 with NF-kappaB on IL-10 promoter. In summary, BRD4 is
      essential for toll like receptor 4 (TLR4)-mediated IL-10 expression, suggesting
      JQ1 could be a potential candidate in regulating IL-10-producing regulatory B
      cells in cancer. [BMB Reports 2017; 50(12): 640-646].

PMID- 29187285
TI  - Allergic Reactions to Tattoo Inks: A New Diagnostic Challenge.

PMID- 29187287
TI  - Relationship between leptin concentrations and disease activity in patients with
      rheumatoid arthritis.
AB  - BACKGROUND AND OBJECTIVE: Multiple studies have found a direct relationship
      between leptin concentrations and disease activity in rheumatoid arthritis.
      PATIENTS AND METHODS: We studied 77 patients with the diagnosis of rheumatoid
      arthritis; the leptin determination was through an enzyme immunoassay. Disease
      activity was assessed by the DAS-28 CRP. A multivariate logistic regression model
      was used to determine the association between significant variables and leptin
      concentrations. RESULTS: 40.3% of the patients were in remission, 41.6% were
      mildly active, 11.7% were moderately active and 6.5% were severely active. The
      results show an independent association between higher concentrations of leptin
      and disease activity (OR 1.7; 95% CI 1.4-3.2; p .03), the number of swollen
      joints (OR 4.6; 95% CI 1.7-8.3; p .000), the number of painful joints (OR 3.4;
      95% CI 1.6-4.6; p .000), and the presence of metabolic syndrome (OR 1.3; 95% IC
      1.2-1,9; p .045). CONCLUSION: The data suggest that serum leptin is elevated in
      patients with active RA.

PMID- 29187288
TI  - Prognostic Relation Between Severity of Diabetes Mellitus (On or Off Insulin) +/-
      Chronic Kidney Disease with Cardiovascular Risk After Percutaneous Coronary
      Intervention.
AB  - The presence of either diabetes mellitus (DM) or chronic kidney disease (CKD) is
      associated with a worse prognosis after percutaneous coronary intervention (PCI).
      It is also known that outcomes in patients treated with insulin (insulin
      requiring type 2 diabetes mellitus [ITDM]) are worse than those who are not on
      insulin (non-insulin type 2 diabetes mellitus [NITDM]). We sought to compare long
      term outcomes in patients who underwent PCI with varying severity of DM with and
      without CKD. We retrospectively studied 17,898 patients who underwent PCI from
      January 2009 to December 2014 in the Mount Sinai Cath Lab. Patients were
      categorized into groups by the presence or the absence of CKD and by the DM
      status (none, NITDM, or ITDM). In the absence of CKD, adjusted hazard ratios (95%
      confidence interval [CI]) for death or myocardial infarction associated with
      NITDM and ITDM were 1.65 (95% CI 1.02 to 2.67) and 3.78 (95% CI 2.23 to 6.40),
      respectively. Analogous risks in the presence of CKD were 3.34 (95% CI 1.99 to
      5.61) and 6.26 (95% CI 3.84 to 10.2). This study shows that irrespective of renal
      status, the need for insulin in the setting of DM identifies a group with
      substantial risk of death or myocardial infarction at 1 year.

PMID- 29187289
TI  - Topsoil radiological characterisation of L-54M reactor surroundings preliminary
      to decommissioning operations.
AB  - The radiological characterization of the topsoil of the L-54M reactor
      surroundings carried out in this work aims at obtaining the reference blank point
      for the forthcoming decommissioning operations and ascertain if unexpected
      radionuclide release occurred during the operational life of the plant.
      Standardised methods have been employed in order to collect representative
      samples and reliable results. Suitable sample pre-treatment procedures were
      applied. Gamma and beta spectrometric analyses were carried out to measure the
      activity concentrations of 60Co 137Cs, 152Eu, 241Am and 90Sr. These have been
      considered as representative radionuclides that could have been originated from
      reactor operations and that could still be present at four decades post reactor
      shutdown.

PMID- 29187290
TI  - Therapeutic position of eliglustat.

PMID- 29187291
TI  - Patient-reported outcomes in patients who undergo total hip arthroplasty after
      periacetabular osteotomy.
AB  - BACKGROUND: There has been constant discussion about whether the clinical outcome
      of THA after periacetabular osteotomy (PAO) is equivalent to that after primary
      total hip arthroplasty (THA). However, there have been few reports about patient
      reported outcomes (PRO) for those who undergo THA after PAO. We compared the pre-
      and postoperative PRO of patients who underwent THA after PAO and those who
      underwent primary THA alone. METHODS: We performed a case-control study. Twenty
      seven patients (29 hips) underwent THA after PAO (osteotomy group); their mean
      age at surgery was 57.2 years, and they underwent postoperative follow-up for a
      mean period of 3.0 years. For the control group, after matching age, sex, and
      Crowe classification, we included 54 patients (58 joints) who underwent primary
      THA for hip dysplasia. Assessment performed preoperatively and at the last follow
      up included the Harris hip score, the Short Form 36 (SF-36) for the Physical
      Component Summary (PCS), Mental Component Summary (MCS), and Role/Social
      Component Summary (RCS) domains, Japanese Orthopaedic Association Hip-Disease
      Evaluation Questionnaire (JHEQ) for pain, movement, and mental health, and the
      visual analog scale (VAS) score of hip pain and satisfaction. RESULTS: The two
      groups demonstrated no significant difference in the preoperative Harris hip
      score, each domain of the SF-36, JHEQ, and the VAS score of hip pain and
      satisfaction. The osteotomy group demonstrated significantly poor Harris hip
      scores for gait and activity, and JHEQ for movement at the last follow-up. There
      was no significant difference in each domain of the SF-36 and the VAS score of
      hip pain and satisfaction at the last follow-up. CONCLUSION: Previous PAO affects
      the quality of physical function in patients who undergo subsequent THA.

PMID- 29187292
TI  - Borrelia miyamotoi: Should this pathogen be considered for the diagnosis of tick
      borne infectious diseases in Spain?
AB  - INTRODUCTION: Borrelia miyamotoi is a tick-borne pathogen belonging to the
      relapsing fever group. It had not been reported from Spain, but its wide
      distribution and the presence of the tick-vector (Ixodes ricinus) made us suspect
      its circulation. The aim of this study was to investigate the presence of
      Borrelia spp. in I. ricinus in Spain. METHODS: A total of 652 I. ricinus nymphs
      collected in northern Spain were processed. The DNA was extracted using
      incubations with ammonium hydroxide. Borrelia spp. DNA was amplified using
      Borrelia-specific PCR assays (glpQ, 16S rRNA and flagellin genes). RESULTS: B.
      miyamotoi was amplified in 4 specimens, and Borrelia burgdorferi sensu lato in 27
      (8 Borrelia afzelii, 7 Borrelia garinii, 8 Borrelia lusitaniae, 3 Borrelia
      valaisiana and 1 B. burgdorferi sensu stricto). CONCLUSION: B. miyamotoi should
      be considered in the differential diagnoses of patients with confirmed or
      suspected tick-bite in Spanish endemic areas for Lyme disease.

PMID- 29187293
TI  - Immune reconstitution inflammatory syndrome in HIV-infected patients with
      Pneumocystis jirovecii pneumonia.
AB  - INTRODUCTION: The incidence of immune reconstitution inflammatory syndrome (IRIS)
      in HIV-infected patients after an episode of Pneumocystis jirovecii pneumonia
      (PJP) seems to be lower than with other opportunistic infections. We conducted an
      observational study in order to determine the incidence, clinical characteristics
      and outcome of patients diagnosed with PJP-related IRIS. METHODS: We conducted an
      observational study of HIV patients diagnosed with PJP-related IRIS from January
      2000 to November 2015. We analyzed epidemiological and clinical characteristics
      as well as laboratory findings. We also carried out a systematic review of
      published cases. RESULTS: Six cases of IRIS out of 123 (4.9%) HIV-infected
      patients with PJP who started ART were diagnosed. All six cases were men with a
      median age of 34 (IQR: 8) years. The six patients developed paradoxical IRIS.
      Subjects younger than 40 years old (p=0.084) and with an HIV-RNA viral load
      >100000 copies/ml (p=0.081) at diagnosis showed a tendency to develop IRIS.
      Thirty-seven published cases of PJP-related IRIS were identified. Although 51% of
      cases involved respiratory failure, no deaths were reported. CONCLUSIONS: PJP
      related IRIS is rare condition compared to other opportunistic infections. It can
      lead to a severe respiratory failure in a significant proportion of cases,
      although no deaths have been reported.

PMID- 29187294
TI  - Nutrient uptake of the uterus during the last third of pregnancy in sows: Effects
      of litter size, gestation stage and maternal glycemia.
AB  - Effects of litter size, pregnancy stage, and glycemia level on uterine uptake of
      energetic nutrients were studied on multiparous sows left intact (CTR; n=6) or
      subjected to unilateral oviduct ligation (LIG; n=6). A jugular vein, a carotid
      artery, and the main vein draining one uterine horn were catheterized. A blood
      flow probe was fitted around the artery irrigating that horn. A meal test and two
      glucose infusion tests (1.15 or 2.30g glucose.(100kg BW)-1min-1) were performed
      at 79, 93, and 106 d of pregnancy. Number of fetuses in the measured uterine horn
      was lower (3.7 vs. 8.0, P<0.001) and newborn piglets were heavier (1.71 vs.
      1.31kg, P=0.04) in the LIG than in the CTR sows. Treatment did not affect uterine
      blood flow (UBF), but UBF/fetus was greater for the LIG treatment (0.57 vs.
      0.32L/min, P=0.003). Glucose and lactate uterine uptakes were never significantly
      affected by treatment. During both tests, uterine uptake of glucose/fetus was
      greater in the LIG sows, which was associated with greater growth rate of their
      fetuses. Glucose and lactate uterine uptakes per fetus increased with glucose
      infusion level (P=0.03) and stage of pregnancy (P=0.04). Extraction coefficient
      of glucose decreased during infusion (P<0.001). Uptakes of NEFA and triglycerides
      were small and decreased during hyperglycemia. Glucose and lactate uptakes
      increased with pregnancy stage due to increased uterine blood flow. Altogether,
      the nutrient uptake per fetus was greater in the sows with few fetuses.

PMID- 29187295
TI  - Comparing Videostroboscopy and Direct Microlaryngoscopy: An Argument for Flexible
      Consent and Operative Plan.
AB  - INTRODUCTION: Office-based evaluation of glottic lesions has progressed
      significantly, but there can still be discrepancies compared with direct
      microlaryngoscopy (DML) in the operating room. We performed a prospective
      evaluation comparing diagnosis of epithelial and lamina propria glottic lesions
      on rigid telescopic strobovideolaryngoscopy (RTS) with DML. METHODS: Fifty
      subjects were enrolled and underwent RTS followed by DML. We compared presence
      and extent (unilateral or bilateral) of lamina propria and epithelial lesions.
      Primary (diagnoses motivating an operation) and secondary (diagnoses not
      requiring an operation) were considered. Changes in diagnosis and operative plan
      based on DML findings were evaluated. RESULTS: Sixty-eight lesions were
      identified on RTS, including 53 primary (15 epithelial, 38 lamina propria) and 15
      secondary diagnoses. RTS was accurate in only 36% of subjects. Ten subjects had a
      different primary pathology identified on DML. A change in surgical management
      occurred in 16% of subjects. CONCLUSIONS: This is the first prospective study
      evaluating how both diagnosis and operative plan for epithelial and lamina
      propria glottic lesions differ based on RTS and DML. Despite significant advances
      in office-based diagnosis of glottic lesions, there are still notable
      limitations. Clinicians should consider these findings when counseling patients
      on interpretation and plan for findings based on RTS. Obtaining a flexible
      surgical consent and counseling patients on the potential for new diagnoses and
      interventions based on DML is warranted.

PMID- 29187296
TI  - Gas adsorption properties of hybrid graphene-MOF materials.
AB  - Nowadays, hybrid porous materials consisting of metal-organic frameworks (MOFs)
      and graphene nanosheets become more and more attractive because of their growing
      applications in adsorption, catalysis and related areas. Incorporation of
      graphene oxide into MOFs can provide benefits such as increased water resistance
      and thermal stability as well as enhanced surface area and adsorption properties.
      Graphene oxide is one of the best additives to other materials owing to its two
      main virtues: high atomic density and large amount of surface functional groups.
      Due to its dense array of atoms, graphene oxide can significantly increase
      dispersion forces in graphene-MOF materials, which is beneficial for adsorption
      of small molecules. This work presents a concise appraisal of adsorption
      properties of MOFs and graphene-MOF hybrids toward CO2, volatile organic
      compounds, hydrogen and methane. It shows that the graphene-MOF materials
      represent an important class of materials with potential applications in
      adsorption and catalysis. A special emphasis of this article is placed on their
      adsorption applications for gas capture and storage. A large number of graphene
      MOF adsorbents has been so far explored and their appraisal could be beneficial
      for researchers interested in the development of hybrid adsorbents for adsorption
      based applications.

PMID- 29187297
TI  - Ca2+ signaling and cell death: Focus on the role of Ca2+ signals in the
      regulation of cell death & survival processes in health, disease and therapy.

PMID- 29187298
TI  - Regional specificity of matrix metalloproteinase-9 expression in the brain: voxel
      level mapping in primary glioblastomas.
AB  - AIM: To investigate the anatomical specificity of matrix metalloproteinase-9 (MMP
      9) expression in glioblastomas by using voxel-based neuroimaging analysis.
      MATERIALS AND METHODS: Clinical information and preoperative magnetic resonance
      images of 133 patients with glioblastomas were reviewed. Evaluation of MMP-9
      expression was performed by using immunohistochemistry. Tumour lesions were
      segmented manually basing on the structural image of each patient, then
      registered to a standard brain atlas. Voxel-based regression analysis was
      subsequently performed to identify the specific brain regions that were
      associated with MMP-9 expression levels. RESULTS: A significantly larger lesion
      volume of T2-hyperintensity was demonstrated in tumours with low MMP-9 expression
      compared to those with high MMP-9 expression (p=0.010). No significant difference
      was found in the lesion volumes of the contrast enhancement areas between the two
      groups (p=0.452). The major correlated cluster with high MMP-9 expression was
      identified in the right frontal lobe, while a cluster located at the posterior
      region of the right lateral ventricle was correlated with low MMP-9 expression.
      CONCLUSION: Voxel-based statistical analysis revealed the anatomical specificity
      of MMP-9 expression levels in glioblastoma. The identified correlation between
      molecular biomarkers and anatomical distribution may increase our understanding
      of the biological characteristics of glioblastoma and provide new insight into
      the molecular subtypes of glioblastoma.

PMID- 29187299
TI  - Diagnostic decision support systems for atrial fibrillation based on a novel
      electrocardiogram approach.
AB  - BACKGROUND: The electrocardiogram (ECG) is one of the most non-invasive
      techniques to give support to the atrial fibrillation (AF) diagnosis. Several
      authors use the temporal difference between two consecutive R waves, a method
      known as RR interval, to perform the AF diagnosis. However, RR interval-based
      analysis does not detect distortions on the other ECG waves. PURPOSE: Thus, the
      present work proposes a diagnostic decision support systems for AF based on
      higher order spectrum analysis of the voltage variation on the ECG.. METHODS: The
      proposed method was used aiming AF classifying. The classifier is composed by two
      screening stages: one based on the average and another on the average deviation
      of kurtosis of the ECG signals. Heartbeat obtained from the MIT-BIH atrial
      fibrillation and MIT-BIH normal were used. RESULTS: ECG signal featured by
      kurtosis outperforms second order statistics based metrics in up to 476 times,
      and up to 110 times above the RR interval. The screening methods obtained
      sensitivity equal to 100% and specificity is up to 84.04%. The two screening
      methods combined provided an AF classifier with an accuracy rate at diagnosis of
      100%. The results presented take into account windows of up to five heartbeats
      and a 99.73% confidence interval. CONCLUSION: The results obtained by the
      proposed method can be used to support decision-making in clinical practices with
      a diagnostic accuracy rate of 90.04% to 100%.

PMID- 29187301
TI  - Teacher? Teacher, I Declare.

PMID- 29187300
TI  - Improvement of the perioperative clinical management by implementation of
      integrated protocol of perioperative substitution of oral anticoagulants.

PMID- 29187302
TI  - A multi-center prospective study randomizing the use of fat emulsion in intensive
      glucose control after allogeneic hematopoietic stem cell transplantation using a
      myeloablative conditioning regimen.
AB  - BACKGROUND & AIMS: Although parenteral nutrition (PN) is often used after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT), there is
      controversy regarding PN management, for instance in the use of fat emulsion and
      glucose control (GC). To clarify these issues, we conducted a multi-center
      prospective study with intensive GC, randomizing the use of fat emulsion after
      allo-HSCT using a myeloablative conditioning regimen. METHODS: The primary
      endpoint was the cumulative incidence of documented infectious disease, namely
      bacterial and fungal infection, at day 100 after allo-HSCT. Between August 2007
      and March 2012, we enrolled 81 patients at 5 centers. Excluding 5 ineligible
      patients, 76 patients received the protocol treatment. The target fasting glucose
      level was 80-110 mg/dL. RESULTS: The median follow-up of surviving patients was
      1796 days. The cumulative incidences of documented infectious disease at day 100
      were 16% (95% confidence interval [CI] 6-29%) in the no-fat group and 19% (95% CI
      8-32%) in the fat group, indicating no significant difference. The mean glucose
      level at 28 days after allo-HSCT was 107 mg/dL in the no-fat group and 111 mg/dL
      in the fat group. Grade 3 hyperglycemia (>250 mg/dL) and grade 3 hypoglycemia
      (<40 mg/dL) occurred in 4 patients each (5.3%). Overall survival and non-relapse
      mortality rates at 4 years were 75% and 11% in the no-fat group and 69% and 8% in
      the fat group, respectively. CONCLUSIONS: Irrespective of the use of fat
      emulsion, the long-term clinical outcomes of the enrolled patients were favorable
      under intensive GC. To further clarify the benefits of GC after allo-HSCT, a
      prospective study randomizing the level of GC is warranted.

PMID- 29187303
TI  - Prevalence and characteristics of chronic kidney disease among Danish adults with
      cystic fibrosis.
AB  - BACKGROUND: With improved prognosis of CF, comorbidities including chronic kidney
      disease (CKD) are becoming increasingly important. Identification of those at
      highest CKD risk is hence a priority. METHODS: In this cross-sectional study,
      adults with CF attending the Copenhagen CF Centre at Rigshospitalet with >=2
      measurements of serum creatinine from 2013 to 2015 were included. Data was
      obtained from an electronic CF database, which contains anonymised clinical and
      laboratory data on all individuals attending the clinic. CKD was defined as a
      confirmed (>=3months apart) estimated glomerular filtration
      rate<=60mL/min/1.73m2. RESULTS: Of 181 individuals, the CKD prevalence was 2.7%
      and increased to 11% after inclusion of lung transplanted patients. Individuals
      with CKD were generally older (median 39 (IQR, 36-45) vs. 31 (IQR, 24-39) years;
      p<0.001), diabetic (86% vs. 41%, p<0.001), with longer median duration of chronic
      pulmonary infection (28.3 (20.0-35.8) vs. 20.0 (9.9-34.7) years; p=0.008) and
      with longer intravenous aminoglycosides use (606 (IQR, 455-917) vs. 273 (IQR, 91
      826) days, p=0.005). CONCLUSIONS: The CKD prevalence is high and related to age,
      diabetes, chronic infection, transplantation and aminoglycosides use. These
      observations call for longitudinal studies investigating CKD predictors in adults
      with CF.

PMID- 29187304
TI  - EBT Payment for Online Grocery Orders: a Mixed-Methods Study to Understand Its
      Uptake among SNAP Recipients and the Barriers to and Motivators for Its Use.
AB  - OBJECTIVE: To examine Supplemental Nutrition Assistance Program (SNAP)
      recipients' use of the first online supermarket accepting Electronic Benefit
      Transfer (EBT) payment. METHODS: In this mixed-methods study, the authors
      collected EBT purchase data from an online grocer and attempted a randomized
      controlled trial in the South Bronx, New York City, followed by focus groups with
      SNAP beneficiaries aged >=18 years. Participants were randomized to shop at their
      usual grocery store or an online supermarket for 3 months. Focus groups explored
      barriers and motivators to online EBT redemption. RESULTS: Few participants made
      online purchases, even when incentivized in the randomized controlled trial.
      Qualitative findings highlighted a lack of perceived control over the online food
      selection process as a key barrier to purchasing food online. Motivators included
      fast, free shipping and discounts. CONCLUSIONS AND IMPLICATIONS: Electronic
      Benefit Transfer for online grocery purchases has the potential to increase food
      access among SNAP beneficiaries, but challenges exist to this new food buying
      option. Understanding online food shopping barriers and motivators is critical to
      the success of policies targeting the online expansion of SNAP benefits.

PMID- 29187305
TI  - Liver resection for colorectal cancer metastases: a comparison of outcomes over
      time in South Australia.
AB  - BACKGROUND: The aim of the current study was to assess outcomes following liver
      resection in metastatic CRC (mCRC) in South Australia across two study periods
      (pre-2006 versus post-2006). METHODS: The South Australian (SA) Clinical Registry
      for mCRC maintains data prospectively on all patients in SA with mCRC diagnosed
      from 01 February 2006. This data was linked with a prospectively collated
      database on liver resections for mCRC from 01/01/1992 to 01/02/2006. The primary
      end point was overall survival. RESULTS: 757 patients underwent liver resection
      for mCRC. Liver resection was performed on 286 patients pre-2006 and 471 patients
      post-2006. The median age of the study population was 62 years, and this was
      similar across both eras. Overall survival was significantly better in the post
      2006 era (hazard ratio HR = 0.45, p = 0.001). Complications (59% pre-2006 versus
      23% post-2006) and transfusion rates (34% pre-2006 versus 2% post-2006) were
      significantly higher in the pre-2006 era. Repeat liver resection rates were
      significantly higher in the post-2006 era (1% pre-2006 versus 10% post-2006).
      CONCLUSIONS: Outcomes following liver resection for mCRC have improved over time,
      with significantly better overall survival in the post-2006 era compared to pre
      2006.

PMID- 29187306
TI  - Contribution of Load Expectations to Neuromechanical Adaptations During a
      Freestyle Lifting Task: A Pilot Study.
AB  - OBJECTIVES: The main goal of this study was to determine to what extent load
      expectations modulate neuromechanical adaptations in individuals with and without
      chronic low back pain (cLBP) when lifting and lowering various loads. The second
      goal was to assess the feasibility of a simple lifting protocol during which
      expectations about loads were manipulated. METHODS: Seventeen participants with
      cLBP and 18 participants without low back pain were asked to lift and lower boxes
      of mild to moderate loads. Two kinds of expectations (lighter and heavier) were
      respectively associated to each experimental block. Self-reported exertion was
      assessed to control for expectations modulation. Erector spinae and vastus
      lateralis electromyography (EMG) activity were recorded and kinematics angle
      calculated. RESULTS: The results showed a main effect of expectations, with loads
      introduced as heavier being associated to a higher exertion compared with loads
      introduced as lighter. EMG activity analyses revealed significant interaction
      involving expectations, movement phase, and loads, as well as significant
      differences between groups. Kinematic angles did not reveal any significant
      effect of expectations nor group during the lifting phase. CONCLUSIONS:
      Psychological factors may contribute to neuromechanical adaptations to low back
      pain. Our preliminary findings show that expectations about loads may result in
      neuromechanical differences between individuals with cLBP and those without cLBP.
      This pilot study showed that testing the manipulation of expectations and EMG
      records was feasible but highlighted the need to go beyond single infrared
      markers to assess kinematics.

PMID- 29187307
TI  - Evaluation of Cross-Cultural Adaptation and Measurement Properties of STarT Back
      Screening Tool: A Systematic Review.
AB  - OBJECTIVE: The purpose of this systematic review was to investigate the extent to
      which the STarT Back Screening Tool (SBST) has been evaluated for (1) the quality
      of translation of evidence for cross-cultural adaptation and (2) the measurement
      properties in languages other than English. METHODS: A systematic search of 8
      databases, including Medline, Embase, CINAHL, PsycINFO, AMED, Scopus, PubMed, and
      Web of Science, was performed. Electronic databases were searched for the period
      between 2008 and December 27, 2016. We included studies related to cross-cultural
      adaptation, including translation and assessment of the measurement properties of
      SBST. Study selection, translation, methodologic and quality assessments, and
      data extraction were performed independently by 2 reviewers. RESULTS: Of the 1566
      citations retrieved, 17 studies were admissible, representing 11 different SBST
      versions in 10 languages. The quadratic weighted kappa statistics of the 2
      reviewers, for the translation, methodologic assessment, and quality assessment
      were 0.85, 0.76, and 0.83, respectively. For translation, only 2 versions
      (Belgian-French and Mandarin) fulfilled all requirements. None of the versions
      had tested all the measurement properties, and when performed, these were found
      to have been conducted inadequately. With regard to quality assessment, overall,
      the included versions had a "Poor" total summary score except 2 (Persian and
      Swiss-German), which were rated as "Fair." CONCLUSIONS: Few versions fully met
      the standard criteria for valid translation, and none of the versions tested all
      the measurement properties. There is a clear need for more accurate cross
      cultural adaptation of SBST and greater attention to the quality of psychometric
      evaluation of the adapted versions of SBST. At this time, caution is recommended
      when using SBST in languages other than English.

PMID- 29187308
TI  - Chiropractic Management for US Female Veterans With Low Back Pain: A
      Retrospective Study of Clinical Outcomes.
AB  - OBJECTIVE: The purpose of this study was to determine if female US veterans had
      clinically significant improvement in low back pain after chiropractic
      management. METHODS: This is a retrospective chart review of 70 courses of care
      for female veterans with a chief complaint of low back pain who received
      chiropractic management through the VA Western New York Healthcare System in
      Buffalo, New York. A paired t test was used to compare baseline and discharge
      outcomes for the Back Bournemouth Questionnaire. The minimum clinically important
      difference was set as a 30% improvement in the outcome measure from baseline to
      discharge. RESULTS: The average patient was 44.8 years old, overweight (body mass
      index 29.1 kg/m2), and white (86%). The mean number of chiropractic treatments
      was 7.9. Statistical significance was found for the Back Bournemouth
      Questionnaire outcomes. The mean raw score improvement was 12.4 points (P <
      .001), representing a 27.3% change from baseline with 47% of courses of care
      meeting or exceeding the minimum clinically important difference. CONCLUSION: For
      our sample of female veterans with low back pain, clinical outcomes from baseline
      to discharge improved under chiropractic care. Although further research is
      warranted, chiropractic care may be of value in contributing to the pain
      management needs of this unique patient population.

PMID- 29187309
TI  - A Finite Element Analysis of Stress Distribution and Disk Displacement in
      Response to Lumbar Rotation Manipulation in the Sitting and Side-Lying Positions.
AB  - OBJECTIVE: This study aimed to investigate stress distribution and disk
      displacement in healthy and degenerated intervertebral disks during simulated
      lumbar rotation manipulation (LRM) in the sitting and side-lying positions.
      METHODS: Three-dimensional (3D) finite element models of healthy, mildly
      degenerated and moderately degenerated L4/5 spinal units were reconstructed.
      Lumbar rotation manipulation in the sitting and side-lying positions were
      simulated, and alterations in stress distribution and disk displacement in the
      lumbar disks were observed. RESULTS: The application of LRM in the sitting or
      side-lying position resulted in a similar stress distribution in healthy, mildly
      degenerated, and moderately degenerated disks. Stress was concentrated at the
      anterior right side of the annulus. In all disks, intradiskal pressure (IDP) and
      maximum von Mises stress were higher during LRM in the sitting position than
      during LRM in the side-lying position. During these manipulations, Intradiskal
      pressure and stress in the annulus of moderately degenerated disks were higher
      than in mildly degenerated disks. Displacement was most obvious in healthy disks.
      CONCLUSIONS: Mildly and moderately degenerated lumbar disks were subject to
      higher stress during LRM in the sitting position than during LRM in the side
      lying position. Intradiskal pressure and the maximum von Mises stress in the
      annulus of moderately degenerated disks increased, suggesting the need for
      caution when treating patients with moderately compromised disks. Although our
      results are in accordance with previously published data, they are simulated and
      preliminary and do not necessarily replicate the clinical condition.

PMID- 29187310
TI  - Changes in Lower Limb Strength and Function Following Lumbar Spinal Mobilization.
AB  - OBJECTIVE: The purpose of this study was to investigate whether grade III passive
      lumbar rotational mobilization on L2-3 can improve hip flexor strength and
      performance in the single-leg triple-hop test in asymptomatic young adults.
      METHODS: Twenty-four participants (12 men, 12 women) aged from 19 to 26 years who
      were positive in the hip flexor "break" test were recruited in this study. They
      were randomly allocated to the treatment group or sham group. Isometric hip
      flexor torque (N.m) and single-leg triple-hop distance (cm) were measured before
      and after a passive lumbar rotational mobilization or a sham intervention.
      RESULTS: After the intervention, both the treatment and sham groups exhibited a
      significant increase in longest hop distance (P = .040 and .044, respectively).
      The treatment group had a significantly higher (3.41 +/- 5.44%) positive
      percentage change in torque than the sham group (-2.36 +/- 5.81%) (P = .02).
      CONCLUSION: The study results indicated a potential effect of grade III passive
      lumbar rotational mobilization in improving hip flexor strength. However, whether
      the improvement in hopping performance was the result of a treatment effect or a
      learning effect could not be determined.

PMID- 29187311
TI  - Intrarater and Inter-rater Reliability of Active Cervical Range of Motion in
      Patients With Nonspecific Neck Pain Measured With Technological and Common Use
      Devices: A Systematic Review With Meta-regression.
AB  - OBJECTIVES: The purpose of this systematic review was to compare intrarater and
      inter-rater reliability of active cervical range of motion (ACROM) measures
      obtained with technological devices to those assessed with low-cost devices in
      patients with nonspecific neck pain. As a secondary outcome, we investigated if
      ACROM reliability is influenced by the plane of the assessed movement. METHODS:
      Medline, Scopus, Embase, the Cochrane Library, CINHAL, PEDro, and gray literature
      were searched until August 2016. Inclusion criteria were reliability design,
      population of adults with nonspecific neck pain, examiners of any level of
      experience, measures repeated at least twice, and statistical indexes on
      reliability. A device was considered inexpensive if it cost less than ?500. The
      risk of bias of included studies was assessed by Quality Appraisal of Reliability
      Studies. RESULTS: The search yielded 35 151 records. Nine studies met all
      eligibility criteria. Their Quality Appraisal of Reliability Studies mean score
      was 3.7 of 11. No significant effect of the type of device (inexpensive vs
      expensive) on intraclass correlation coefficient (ICC) was identified for
      intrarater (ICC = 0.93 vs 0.91; P > .99) and inter-rater reliability (ICC = 0.80
      vs 0.87; P > .99). The plane of movement did not affect inter-rater reliability
      (P = .11). Significant influences were identified with intrarater reliability (P
      = .0001) of inexpensive devices, where intrarater reliability decreased (P = .01)
      in side bending, compared with flexion-extension. CONCLUSIONS: The use of
      expensive devices to measure ACROM in adults with nonspecific neck pain does not
      seem to improve the reliability of the assessment. Side bending had a lower level
      of intrarater reliability.

PMID- 29187312
TI  - Comparison of Pressure Pain Thresholds in Upper Trapezius and Temporalis Muscles
      Trigger Points Between Tension Type Headache and Healthy Participants: A Case
      Control Study.
AB  - OBJECTIVE: To date, the minimum clinical differences (MCDs) in the pressure pain
      thresholds (PPTs) of the upper trapezius and temporalis muscles have not yet been
      established in participants with tension-type headache (TTH). The purpose of the
      study was to evaluate the MCDs of the PPTs of the upper trapezius and temporalis
      in participants with TTH and those without TTH. METHODS: The sample comprised 120
      participants with TTH (n = 60; mean [standard deviation] years = 38.30 [10.05])
      and without TTH (n = 60; 34 [8.20]). The participants were recruited from an
      outpatient clinic in Spain from 2014 to 2016. The PPTs of the most hyperalgesic
      trigger points of the upper trapezius and temporalis were assessed. RESULTS:
      There were statistically significant differences, mean (standard deviation)
      kg/cm2, for the right upper trapezius PPT (P < .001; 1.52 [0.35] vs 2.37 [0.49]),
      the left upper trapezius PPT (P < .001; 1.53 [0.36] vs 2.29 [0.49]), the right
      temporalis PPT (P = .008; 1.56 [0.31] vs 1.72 [0.33]), and the left temporalis
      PPT (P = .001; 1.57 [0.27] vs 1.74 [0.30]) between participants with and without
      TTH, respectively. CONCLUSIONS: The PPT MCDs for the right and left upper
      trapezius and the right and left temporalis were 0.85, 0.76, 0.16, and 0.17
      kg/cm2, respectively, for the clinical management of trigger points in
      participants with TTH.

PMID- 29187313
TI  - Immediate Changes in Resting and Contracted Thickness of Transversus Abdominis
      After Dry Needling of Lumbar Multifidus in Healthy Participants: A Randomized
      Controlled Crossover Trial.
AB  - OBJECTIVE: The purpose of this study was to investigate changes in resting and/or
      contraction thickness of the transversus abdominis (TrA) muscle after dry
      needling (DN) of the lumbar multifidus (LM) in asymptomatic participants.
      METHODS: A randomized controlled laboratory trial with crossover design was
      performed. Forty-seven healthy individuals who had not experienced low back pain
      in the previous 6 months were randomly assigned to receive DN to the LM or a sham
      DN intervention. Participants received both interventions separated at least 7
      days apart. They were instructed on how to perform a concentric contraction of
      TrA. Resting and contraction thicknesses of the TrA were obtained through real
      time ultrasound measurements before and immediately after each intervention by an
      assessor blinded to the intervention received. Data from 4 individuals had to be
      excluded because of poor image quality. RESULTS: Two-way analysis of variance
      revealed a significant contraction with treatment interaction (F[1,42] = 11.489;
      P = .002). Simple main effects using paired-samples t tests and a Bonferroni post
      hoc analysis revealed differences in contracted states of the TrA for DN vs sham
      DN (P = .009) and between contracted and resting states for the DN group (P =
      .001): after DN, TrA thickness at rest exhibited a mean decrease of 0.03 cm and a
      mean increase of 0.05 cm during contraction. CONCLUSION: This study suggests that
      application of DN to LM was accompanied by a decreased resting thickness and an
      increased contraction thickness of the TrA in asymptomatic participants.

PMID- 29187314
TI  - What is stressful for females? Differential effects of unpredictable
      environmental or social stress in CD1 female mice.
AB  - Stressful life events are a major factor in the etiology of several diseases,
      such as cardiovascular, inflammatory and psychiatric disorders (i.e., depression
      and anxiety), with the two sexes greatly differing in vulnerability. In humans
      and other animals, physiological and behavioral responses to stress are strongly
      dependent on gender, and conditions that are stressful for males are not
      necessarily stressful for females. Hence the need of an animal model of social
      chronic stress specifically designed for females. In the present study we aimed
      to compare the effects of two different chronic stress procedures in female mice,
      by investigating the impact of 4weeks of nonsocial unpredictable, physical stress
      by the Chronic Mild Stress paradigm (CMS; Exp.1) or of Social Instability Stress
      (SIS; Exp.2) on physiological, endocrine and behavioral parameters in adult
      female mice. CMS had a pronounced effect on females' response to novelty (i.e.,
      either novel environment or novel social stimulus), body weight growth and
      hormonal profile. Conversely, 4weeks of social instability did not alter females'
      response to novelty nor hormonal levels but induced anhedonia. Our findings thus
      showed that female mice were more sensitive to nonsocial stress due to
      unpredictable physical environment than to social instability stressors. Neither
      of these stress paradigms, however, induced a consistent behavioral and
      physiological stress response in female mice comparable to that induced by
      chronic stress procedures in male mice, thus confirming the difficulties of
      developing a robust and validated model of chronic psychosocial stress in female
      mice.

PMID- 29187316
TI  - Immunity and Inflammation: From Jekyll to Hyde.
AB  - The immune system is the defense system of the host that protects it from foreign
      pathogens. Inflammation is one of the key processes that alert the immune system
      but when loss of regulation occurs, a long-term chronic inflammation settles and
      is likely to be detrimental to the host. Most age-related diseases are linked to
      a disequilibrium of circulating inflammatory molecules. We could use the analogy
      of "Dr Jekyll' representing the expected inflammation and immune response in
      general and the "Mr. Hyde" effect represented by the other face of inflammation,
      when it is dysregulated. This review aims to cover how immunity, inflammation and
      persistent infection are associated and some aspects that future studies should
      look into such as tissue-specific immunity and interventions. Having this
      knowledge will enable us to prevent inflammation to lose its regulatory network,
      which could potentially increase the health-span and a better quality of life for
      the growing elderly population.

PMID- 29187315
TI  - Molecular characterization of a human G20P[28] rotavirus a strain with multiple
      genes related to bat rotaviruses.
AB  - Group A rotaviruses are the major cause of severe gastroenteritis in the young of
      mammals and birds. This report describes characterization of an unusual G20P[28]
      rotavirus strain detected in a 24month old child from Suriname. Genomic sequence
      analyses revealed that the genotype constellation of the Suriname strain
      RVA/Human-wt/SUR/2014735512/2013/G20P[28] was G20-P[28]-I13-R13-C13-M12-A23-N13
      T15-E20-H15. Genes VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5 were recently
      assigned novel genotypes by the Rotavirus Classification Working Group (RCWG).
      Three of the 11 gene segments (VP7, VP4, VP6) were similar to cognate gene
      sequences of bat-like human rotavirus strain Ecu534 from Ecuador and the VP7,
      NSP3 and NSP5 gene segments of strain RVA/Human-wt/SUR/2014735512/2013/G20P[28]
      were found to be closely related to gene sequences of bat rotavirus strain
      3081/BRA detected in Brazil. Although distantly related, the VP1 gene of the
      study strain and bat strain BatLi09 detected in Cameroon in 2014 are
      monophyletic. The NSP1 gene was found to be most closely related to human strain
      QUI-35-F5 from Brazil. These findings suggest that strain RVA/Human
      wt/SUR/2014735512/2013/G20P[28] represents a zoonotic infection from a bat host.

PMID- 29187317
TI  - Establishing ultrasound based transient elastography cutoffs for different stages
      of hepatic fibrosis and cirrhosis in Egyptian chronic hepatitis C patients.
AB  - BACKGROUND AND STUDY AIM: Transient elastography is widely used to assess
      fibrosis stage in chronic hepatitis C (CHC). We aimed to establish and validate
      different transient elastography cut-off values for significant fibrosis and
      cirrhosis in CHC genotype 4 patients. PATIENTS AND METHODS: The data of 100
      treatment-naive CHC patients (training set) and 652 patients (validation set)
      were analysed. The patients were subjected to routine pretreatment laboratory
      investigations, liver biopsy and histopathological staging of hepatic fibrosis
      according to the METAVIR scoring system. Transient elastography was performed
      before and in the same week as liver biopsy using FibroScan (Echosens, Paris,
      France). Transient elastography results were correlated to different stages of
      hepatic fibrosis in both the training and validation sets. RESULTS: ROC curves
      were constructed. In the training set, the best transient elastography cut-off
      values for significant hepatic fibrosis (>=F2 METAVIR), advanced hepatic fibrosis
      (>=F3 METAVIR) and cirrhosis (F4 METAVIR) were 7.1, 9 and 12.2 kPa, with
      sensitivities of 87%, 87.5% and 90.9% and specificities of 100%, 99.9% and 99.9%,
      respectively. The application of these cut-offs in the validation set showed
      sensitivities of 85.5%, 82.8% and 92% and specificities of 86%, 89.4% and 99.01%
      for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis,
      respectively. CONCLUSION: Transient elastography performs well for significant
      hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, with validated cut
      offs of 7.1, 9 and 12.2 kPa, respectively, in genotype 4 CHC patients.

PMID- 29187319
TI  - Ethnoveterinary botanical survey of medicinal plants in Abergelle, Sekota and
      Lalibela districts of Amhara region, Northern Ethiopia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The study area is known by its huge livestock
      resources with extensive ethnoveterinary practice. This knowledge was not
      documented scientifically until we proposed to do so. The study can aid in future
      planning of endangered species conservation as well as for experimental studies
      in search of modern pharmacotherapy. AIM OF THE STUDY: The study objective was to
      understand the extent of ethnoveterinary practice, methods, types of medicinal
      plant species used and to generate a comprehensive baseline data that can be used
      as a basis for further studies. MATERIALS AND METHODS: The survey was conducted
      from November 2015 to December 2016 in different seasons of the year. Participant
      selection process was started by recording all the known animal healers by
      assigning village leaders, animal health professionals, and research field
      assistants to record all animal healers of the area. Assigned personals
      communicate elders, and other members of the communities of the 3 districts to
      recommend the traditional animal healer they know. Accordingly, 60 participants
      were recommended by the peoples of the 3 districts and the interview process was
      conducted with a semi-structured questionnaire to record the knowledge of
      ethnoveterinary practice of the 60 healers. After finishing the interview
      process, researchers had a walk in the woods, mountains, and rivers with
      informants to collect medicinal plants. Standard procedures were followed for the
      record of plant materials, drying, and pressing of plant specimens was performed
      in the field followed by labeling with the local name, collection date,
      collection site, and identification code. RESULTS: A total of 53 medicinal plants
      that belong to 31 families used in treating 22 kinds of livestock diseases were
      identified. CONCLUSION: We found the area has a huge resource of ethnoveterinary
      medicinal plants. However, overuse and environmental anthropological change
      resulted in the scarcity of medicinal plants. This condition was complained by
      healers during the survey.

PMID- 29187318
TI  - Instructing children with Autism Spectrum Disorder: Examining swim instructors'
      knowledge building experiences.
AB  - BACKGROUND: Although there has been a notable increase in Autism Spectrum
      Disorder (ASD) diagnoses over the past twenty years, children with ASD continue
      to be underrepresented in physical activity opportunities. Swimming lessons have
      been suggested as an ideal form of physical activity for this population, but
      studies exploring instructors' experiences gaining knowledge specific for
      instructing these swimmers remains limited. Research in this area is warranted,
      as drowning is a leading injury cause of death for persons with ASD. OBJECTIVE:
      The purpose of this brief report was to examine swim instructors' preferred
      knowledge sources for building their individual swimming lessons, catered to
      swimmers with ASD. Moreover, this study aimed to provide context specific
      insights for instructors and instructor educators to increase new and future
      instructors' preparedness for meeting the needs of this population. METHODS:
      Three recreational swim instructors were recruited for this qualitative study.
      Data were collected using a demographic questionnaire, observations, and semi
      structured interviews. Analysis was completed using Braun & Clarke's guide for
      thematic analysis. RESULTS: The results indicated that swim instructors' sources
      for building knowledge included: learning from peers/mentors, receiving support
      from parents/caregivers, and participating in additional certification programs
      or training. CONCLUSION: With a more extensive understanding of instructors'
      knowledge building experiences, instructor educators may integrate this knowledge
      into future development programs to prepare a greater number of trained
      individuals to facilitate physical activities for children with ASD.

PMID- 29187320
TI  - Progressive practice promotes motor learning and repeated transient increases in
      corticospinal excitability across multiple days.
AB  - BACKGROUND: A session of motor skill learning is accompanied by transient
      increases in corticospinal excitability(CSE), which are thought to reflect acute
      changes in neuronal connectivity associated with improvements in sensorimotor
      performance. Factors influencing changes in excitability and motor skill with
      continued practice remain however to be elucidated. OBJECTIVE/HYPOTHESIS: Here we
      investigate the hypothesis that progressive motor practice during consecutive
      days can induce repeated transient increases in corticospinal excitability and
      promote motor skill learning. METHODS: Changes in motor performance and CSE were
      assessed during 4 consecutive days of skill learning and 8 days after the last
      practice session. CSE was assessed as area under recruitment curves(RC) using
      transcranial magnetic stimulation(TMS). Two groups of participants(n = 12)
      practiced a visuomotor tracking-task with task difficulty progressively increased
      with individual proficiency(PPG) or with the same task level throughout all 4
      days(NPPG). RESULTS: Progressive practice resulted in superior motor learning
      compared to NPPG(p < 0.001). Whereas NPPG displayed increased CSE following only
      the first day of practice(p < 0.001), progressive motor practice was accompanied
      by increases in CSE on both the first and the final session of motor practice(p =
      0.006). Eight days after ended practice, the groups showed similar CSE, but PPG
      maintained superior performance at a skilled task level and transfer task
      performance(p < 0.005,p = 0.029). CONCLUSION: The results demonstrate that
      progressive practice promotes both motor learning and repeated increases in CSE
      across multiple days. While changes in CSE did not relate to learning our results
      suggest that they signify successful training. Progressive practice is thus
      important for optimizing neurorehabilitation and motor practice protocols in
      general.

PMID- 29187321
TI  - Impaired neurogenesis and associated gliosis in mouse brain with PEX13
      deficiency.
AB  - Zellweger syndrome (ZS), a neonatal lethal disorder arising from defective
      peroxisome biogenesis, features profound neuroanatomical abnormalities and brain
      dysfunction. Here we used mice with brain-restricted inactivation of the
      peroxisome biogenesis gene PEX13 to model the pathophysiological features of ZS,
      and determine the impact of peroxisome dysfunction on neurogenesis and cell
      maturation in ZS. In the embryonic and postnatal PEX13 mutant brain, we
      demonstrate key regions with altered brain anatomy, including enlarged lateral
      ventricles and aberrant cortical, hippocampal and hypothalamic organization. To
      characterize the underlying mechanisms, we show a significant reduction in
      proliferation, migration, differentiation, and maturation of neural progenitors
      in embryonic E12.5 through to P3 animals. An increasing reactive gliosis in the
      PEX13 mutant brain started at E14.5 in association with the pathology. Together
      with impaired neurogenesis and associated gliosis, our data demonstrate increased
      cell death contributing to the hallmark brain anatomy of ZS. We provide unique
      data where impaired neurogenesis and migration are shown as critical events
      underlying the neuropathology and altered brain function of mice with peroxisome
      deficiency.

PMID- 29187323
TI  - The prescription at the elder person: a difficult art.

PMID- 29187324
TI  - Pain in the elderly and cognition: state of play.
AB  - Cognitive impairment is commonly associated with the pain experience. This
      deterioration regarding several cognitive domains such as attention, speed of
      information processing, memory, learning and executive functions, represents a
      major obstacle to daily activities and mobility especially in the elderly for
      whom a decrease in mobility is a significant risk factor for death and
      disability. Regarding the demographic rising in the elderly population expected
      by 2050 (the proportion of persons aged 60 and above is expected to double
      according to ONU estimate) and the high prevalence of pain in this age reaching
      80% in nursing homes, clinicians should be better aware of the links between pain
      and cognition in this population's segment so that they offer each patient an
      appropriate treatment. The objective of this review is to draw up an inventory of
      knowledge and differences between general population and elderly population on
      the complex relationship between these two phenomena, the contribution of imaging
      in the understanding of this link and the role of attitudes, beliefs and opioids
      on pain perception and cognition.

PMID- 29187322
TI  - Sanitary Sewer Overflows and Emergency Room Visits for Gastrointestinal Illness:
      Analysis of Massachusetts Data, 2006-2007.
AB  - BACKGROUND: Sanitary sewer overflows (SSOs) occur when untreated sewage is
      discharged into water sources before reaching the treatment facility, potentially
      contaminating the water source with gastrointestinal pathogens. OBJECTIVES: The
      objective of this paper is to assess associations between SSO events and rates of
      gastrointestinal (GI) illness in Massachusetts. METHODS: A case-crossover study
      design was used to investigate association between SSO events and emergency room
      (ER) visits with a primary diagnosis of gastrointestinal (GI) illness in
      Massachusetts for 2006-2007. ER visits for GI were considered exposed if an SSO
      event occurred in the county of residence within three hazard periods, 0-4 d, 5-9
      d, or 10-14 d, before the visit. A time-stratified bidirectional design was used
      to select control days for each ER visit on the same day of the week during the
      same month. Fixed effect logistic regression models were used to estimate the
      risk of ER visits following the SSO event. RESULTS: During the study period,
      there were 270 SSO events for northeastern Massachusetts and 66,460 ER admissions
      with GI illness listed as the primary diagnostic code. The overall odds ratio
      (OR) for ER visits for GI illness was 1.09 [95% confidence interval (CI): 1.03,
      1.16] in the 10-14 d period following an SSO event, with positive ORs for all age
      groups and for three of the four counties. The 0-4 d and 5-9 d periods following
      an SSO event were not associated with ER visits for GI illness overall, and
      associations by county or age were inconsistent. CONCLUSIONS: We demonstrated an
      association between SSO events and ER visits for GI illness using a case
      crossover study design. In light of the aging water infrastructure in the United
      States and the expected increase in heavy rainfall events, our findings suggest a
      potential health impact associated with sewage overflows.
      https://doi.org/10.1289/EHP2048.

PMID- 29187325
TI  - Relevance of G8 scale in referring elderly patients with aortic stenosis
      requiring a TAVI for a geriatric consultation.
AB  - Aortic stenosis (AS) may soon become a significant public health issue. Referring
      elderly suffering from aortic stenosis for a transcatheter aortic valve
      implantation (TAVI) versus surgical valve replacement might be difficult and
      requires a multidisciplinary staff. G8 is a geriatric screening scale for
      frailty, validated in oncogeriatry. We study sensibility and specificity of G8
      used by cardiologists in comparison to a comprehensive geriatric assessment (CGA)
      performed by geriatrician. Prospective study, from February to July 2015, in
      Bordeaux university Hospital, France. Every elderly admitted for a TAVI had a G8
      scale performed by cardiologist and CGA by a geriatrician in blind. Comorbidities
      were assessed using Cumulative Illness Rating Scale in his geriatric version
      (CIRS-G). CGA was abnormal if: MMSE <24/30 or GDS >=7/15 or ADL <=5/6 or IADL
      <=7/8 or TUG >=20 seconds or if malnutrition was noticed. G8 was abnormal if
      <=14/17. We calculated sensibility, specificity, positive and negative predictive
      value in comparison to gold-standard CGA. 49 patients were included (55.1% women,
      mean age 84.8 years old). Nearly half of the patients (48.96%) had multiple
      comorbidities (CIRS G score >3 for at least three items excluding the cardiology
      item). 38 CGA were abnormal (77.55%) and 41 G8 (83.67%). G8 had a sensibility of
      100% (IC 95% [0.9-1]), a specificity of 72.7% (IC 95% [0.43-0.9]), a positive
      predictive value of 92.6% and a negative prospective value of 100% (IC: 95%). G8
      scale seems to be an efficient geriatric screening tool for frailty in elderly
      undergoing TAVI in comparison to CGA. Simple and useful, G8 scale could be
      performed by cardiologists in older patients with AS for identifying patients
      with a geriatric risk profile in consultation before surgery. Further studies
      with bigger samples are needed to confirm these results.

PMID- 29187326
TI  - Decision making affecting care of older people with cancer: a comparison between
      general practitioners and oncologists in Lorraine.
AB  - The main objective of this study is to identify the decision criteria of general
      practitioners and oncologists in the management of older patients with cancer in
      Lorraine. The secondary objectives are to identify the difficulties encountered
      and to propose solutions to improve health path of these patients. 2,995 post
      mail questionnaires were sent to all general practitioners and oncologists in
      Lorraine. Some decision criteria differ between general practitioners and
      oncologists: civilian age and accessibility to a specialized advice for general
      practitioners; type of cancer, nutritional status, application of best practice
      recommendations, and multidisciplinary discussion for oncologists. The main
      difficulties reported are organizational and relate to time interval before
      specific care beginning, accessibility to a medical specialist, and post
      diagnosis such link between primary care and hospital. General practitioners and
      oncologists mainly agree with the difficulties encountered and the solutions to
      find, even if some decision criteria differences are highlighted. The training of
      professionals remains the major lever for improvement of medical practices.

PMID- 29187327
TI  - Endoscopic retrograde cholangiopancreatography in the elderly over 75 years old:
      a survey.
AB  - Whilst endoscopic retrograde cholangiopancreatography (ERCP) is being practiced
      on increasingly older patients, its benefits have not been well studied. This
      study assessed the clinical benefit of ERCP for subjects aged 75 and over,
      including follow-up at 3 months of geriatric functional parameters and lifestyle.
      This is a prospective mono-centric, cohort study. All patients aged 75 and over
      receiving ERCP were enrolled and monitored for a period of 3 months. We recorded
      53 inclusions between November 1st 2014 to 31 May 2015. Our "ill-type" was a
      fragile polypathology woman of 85 years, living at home, with loss of autonomy
      for instrumental activities of daily living (IADL). Lithiasis was diagnosed in
      56.6% of cases, and malignant stenosis in 35.8% of cases. The success rate was
      88.7% with a 5.7% complication rate. At 3 months, we observed no clinically
      significant change in ADL parameters, IADL and lifestyle. Our follow-up data
      support the practice of ERCP in geriatric populations.

PMID- 29187328
TI  - Survey of the prescription of step-2 analgesics in persons aged 75 years and
      older in general practitioners.
AB  - Although step-2 analgesics (S2A) are recommended when step-1 analgesics (S1A) are
      ineffective or in cases of moderate to severe pain, their efficacy varies. This
      study evaluated the place attributed by general practitioners (GPs) to S2A in the
      treatment of nociceptive pain in elderly persons (EP). Descriptive, transversal
      and declarative study conducted among GPs in Burgundy. In total, 115 GPs took
      part in the survey. Among these, 60.8% had at least one consultation/day for
      pain. After paracetamol, which was systematically preferred, 56.4% prescribed S2A
      for EP. The reasons for prescribing S2A included pain not relieved by S1A in 93%
      of cases, another medical treatment or not (42.6%), or the existence of moderate
      to severe pain (31.3%). The use of S2A was more frequent in acute pain (79.1%)
      than in chronic pain (53%). Among GPs, 77.4% initially prescribed the minimal
      effective dose. GPs were reluctant to prescribe S2As for the following reasons:
      poor tolerance (78.3%) and the fear of severe adverse effects (57.4%). The most
      frequently cited adverse effects were nausea/vomiting and constipation by 66.1%
      of GPs. Nonetheless, 73.9% thought that S2As were necessary for EPs requiring
      outpatient care. Although the benefit/risk ration of S2As is controversial and
      their analgesic efficacy seems to be more variable than that of low-dose
      morphine, they have an important place in the therapeutic arsenal of GPs to treat
      pain in EP.

PMID- 29187330
TI  - Editorial.

PMID- 29187329
TI  - Impact of therapeutic education with a written document on treatments knowledge
      and adherence among elderly patients. Results of a pilot study.
AB  - : Olders patients are exposed to iatrogenic risk as they are often frail, with
      multiple pathologies and therefore polymedicated. The objective of this study was
      to evaluate the knowledge of treatment in the elderly before and after a time of
      oral therapeutic education accompanied by the submission of a written educational
      support. The impact of that education on the adhesion was also evaluated.
      METHODS: We've included patients aged at least 75 years old, living at home, and
      managing themselves their treatment. At study entry, patients were evaluated by
      their regular physician about knowledge and compliance of their treatment and
      were receiving therapeutic education time. Three months later, knowledge and
      adherence to treatment were re-evaluated by the treating physician during an
      interview. The adhesion was evaluated using the Morisky score. RESULTS: 89
      subjects were enrolled between May and October 2015. The average age was 81.9
      years old and most patients were autonomous. We observed an improvement in the
      knowledge three months after the intervention (drug names: 67% vs 76%, p=0.048;
      indications: 80% vs 91%, p=0.010; dosages: 83% vs 92%, p=0.003). Patient
      medication adherence evaluated by the Morisky score was significantly improved
      (p=0.0036). CONCLUSION: Patient education improves knowledge and adherence to
      treatment among the older subjects and could improve the safety of prescription
      and reduce iatrogenic risk in geriatrics.

PMID- 29187331
TI  - Difficulties in the management of elderly migrants.
AB  - Based on an in-depth case study, the authors of this paper highlight the
      difficulties faced by caregivers in the psychogeriatric care for elderly
      migrants. They show how both the history of emigration and the migratory
      experience can make this management complex. They articulate their reflection on
      the difficulties of diagnosis and therapeutic relationship, on the linguistic
      barrier around the question of old age in migration context. For the effective
      management of the elderly migrant, the authors suggest a strengthening of
      intercultural skills for caregivers.

PMID- 29187332
TI  - Designing gardens for people with dementia: literature review and evidence-based
      design conceptual frame.
AB  - More and more dwelling facilities for people with dementia invest gardens as
      convivial, resourceful, and relational places. However, there is a demand for
      scientific evidence of such statements. The aims of this literature review are to
      enlighten scientific evidence concerning uses and therapeutic virtues of garden
      for people with dementia, and to contribute to an evidence-based design approach
      by identifying key dimension of garden design. Twenty two articles were selected
      for this literature review and six clusters were identified. These clusters are
      discussed in a conceptual frame and discussed in an environment-behaviour
      approach.

PMID- 29187333
TI  - Toward a clinic of temporality?
AB  - The discovery of time cells has expanded our knowledge in the field of spatial
      and temporal information coding and the key role of the hippocampus. The internal
      clock model complemented with the attentional gate model allows a more in-depth
      understanding of the perception of time. The motor representation of duration is
      ensured by the basal ganglia, while the cerebellum synchronizes short duration
      for the movement. The right prefrontal cortex seemingly intervenes in the
      handling of temporal information in working memory. The temporal lobe ensures the
      comparison of durations, especially the right lobe for the reference durations
      and the medial lobe for the reproduction of durations in episodic memory. During
      normal aging, the hypothesis of slowing of the temporal processor is evoked when
      noting the perception of the acceleration of the passage of time that seemingly
      occurs with advancing age. The various studies pertaining specifically to time
      cognition, albeit heterogeneous in terms of methodology, attest to the wide
      ranging disturbances of this cognitive field during the course of numerous
      disorders, whether psychiatric - depression and schizophrenia notably - or
      neurological. Hence, perturbations in temporality are observed in focal brain
      lesions and in subcortical disorders, such as Parkinson's disease or Huntington's
      chorea. Alzheimer's disease represents a particularly fertile field of
      exploration with regard to time cognition and temporality. The objectified
      deconstruction of temporal experience provides insights into the very processes
      of temporality and their nature: episodic, semantic and procedural. In addition
      to exploration based on elementary stimuli, one should also consider the time
      lived, i.e. that of the subject, to better understand cognition as it relates to
      time. While the temporal dimension permeates the whole cognitive field, it
      remains largely neglected: integration of a genuine time cognition and
      temporality clinic in daily practice remains to be implemented.

PMID- 29187334
TI  - Cognitive profile in prodromal disease (dementia) with Lewy bodies.
AB  - This paper reviews findings on cognition in prodromal dementia with Lewy bodies
      (DLB). The issue of differential diagnosis between DLB and Alzheimer's disease
      (AD) on the one hand, and Parkinson's disease (PD) on the other hand, at
      prodromal stages of the diseases is discussed. The cognitive profile of prodromal
      DLB is also evaluated in terms of cognitive deficits and " cognitive weaknesses "
      (low performances although in normal range). Findings suggest that visuo
      constructive tests and verbal fluency are particularly relevant to dfferentiate
      DLB from AD. A similar finding is evident when comparing prodromal DLB and PD.
      Attentional, executive and visuo-constructive tests appear to be the best
      predictor of DLB. Moreover, investigation of the cognitive profile in prodromal
      DLB highlights that cognitive difficulties are diffuse. Yet it appears that
      difficulties in cortical visual abilities and executive functions are prominent
      and likely to account, at least partially, for cognitive disturbances observed in
      neuropsychological tests assessing other cognitive functions.

PMID- 29187335
TI  - Autobiographical memory compromise in Alzheimer's disease: a cognitive and
      clinical overview.
AB  - Autobiographical memory refers to memory for personal information. The compromise
      of autobiographical memory in Alzheimer's disease (AD) results in a loss of
      knowledge about events and facts that defined the patients' life, and
      consequently, degradation of their self-knowledge and sense of identity. The
      compromise of autobiographical memory in AD can be attributed to a diminished
      subjective experience of memory and a diminished sense of the self. Our review
      provides a comprehensive overview of cognitive and clinical processes that may be
      involved in difficulties to retrieve autobiographical memories in Alzheimer's
      disease. Our review also proposes a theoretical model according to which, the
      diminished ability to retrieve contextual information and the overgenerality of
      recall result in a diminished subjective experience of past and future thinking.
      Besides its theoretical contribution, our review proposes clinical applicability
      for evaluation and rehabilitation of autobiographical memory in AD.

PMID- 29187337
TI  - PRR signaling during in vitro macrophage differentiation from progenitors
      modulates their subsequent response to inflammatory stimuli.
AB  - Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells
      (HSPCs) to differentiate along the myeloid lineage in vitro and also in vivo
      following infection. In this study, we used an in vitro model of HSPC
      differentiation to investigate the functional consequences (cytokine production)
      that exposing HSPCs to various pathogen-associated molecular patterns (PAMPs) and
      Candida albicans cells have on the subsequently derived macrophages. Mouse HSPCs
      (Lin- cells) were cultured with GM-CSF to induce macrophage differentiation in
      the presence or absence of the following pattern recognition receptor (PRR)
      agonists: Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand), depleted zymosan (which only
      activates Dectin-1), or inactivated C. albicans yeasts (which activate several
      PRRs, mainly TLR2 and Dectin-1). Our data show that only pure TLR2 ligand
      exposure (transient and continuous) impacts the inflammatory function of GM-CSF
      derived macrophages, because Pam3CSK4-exposed HSPCs generate macrophages with a
      diminished ability to produce inflammatory cytokines. Interestingly, the Pam3CSK4
      induced tolerance of macrophages (by transient exposure of HSPCs) is reinforced
      by subsequent exposure to C. albicans cells in GM-CSF-derived macrophages;
      however, the induced tolerance is partially reversed in M-CSF-derived
      macrophages. Therefore, the ability of macrophages to produce inflammatory
      cytokines is extremely dependent on how the HSPCs from which they are derived
      receive and integrate multiple microenvironmental signals (PRR ligands and/or
      CSFs).

PMID- 29187338
TI  - Effects of interleukin 17A (IL-17A) neutralization on murine hepatitis virus (MHV
      A59) infection.
AB  - Mice infected with mouse hepatitis virus A59 (MHV-A59) develop hepatitis and
      autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH),
      a fact closely related to the release of alarmins such as uric acid and/or high
      mobility group box protein 1 (HMGB1). We studied the effect of neutralizing
      monoclonal antibodies (MAb) against IL-17A in our model of mouse MHV-A59
      infection. MAb anti-IL-17F and anti-IFNgamma were used to complement the study.
      Results showed that transaminase levels markedly decreased in MHV-A59-infected
      mice treated with MAb anti-IL-17A whereas plasmatic Ig concentration sharply
      increased. Conversely, MAb anti-IL-17F enhanced transaminase liberation and did
      not affect Ig levels. Serum IFNgamma was detected in mice infected with MHV-A59
      and its concentration increased after MAb anti-IL-17A administration. Besides,
      MAb anti-IFNgamma greatly augmented transaminase plasmatic levels. IL-17A
      neutralization did not affect MHV-A59-induction of HMGB1 liberation and slightly
      augmented plasmatic uric acid concentration. However, mice treated with the MAb
      failed to produce autoAb to FAH. The above results suggest a reciprocal
      regulation of Th1 and Th17 cells acting on the different MHV-A59 effects. In
      addition, it is proposed that IL-17A is involved in alarmins adjuvant effects
      leading to autoAb expression.

PMID- 29187339
TI  - Sophocarpine suppress inflammatory response in human fibroblast-like synoviocytes
      and in mice with collagen-induced arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting nearly 1% of
      adults worldwide. This study aimed to investigate whether sophocarpine is a
      potential drug for treating RA. The cytotoxicity of sophocarpine to RA-fibroblast
      like synoviocytes (FLSs) was evaluated using 3-[4,-dimethylthiazol-2-y]-2,5
      diphenyl-tetrazolium bromide (MTT) assays kit and released lactate dehydrogenase
      (LDH) assays. The transcription of proinflammatory cytokines in RA-FLSs was
      analyzed by reverse transcription and real-time polymerase chain reaction (RT
      PCR). The proteins levels were further verified by enzyme-linked immunosorbent
      assay (ELISA). The alterations in the mediators of mitogen-activated protein
      kinase (MAPK) and nuclear factor kappaB (NF-kappaB) signaling pathways were
      tested by western blotting. The clinical effects of sophocarpine were evaluated
      in type II collagen-induced arthritis (CIA) in DBA-/1 mouse model by scoring
      their clinical responses, synovitis, and cartilage destructions, and ELISA was
      employed to analyze the concentrations of proinflammatory cytokines in the serum
      of CIA mice. The results showed that sophocarpine contained low cytotoxicity to
      RA-FLS cells, and it was capable to downregulate the expressions of LPS-induced
      proinflammatory cytokines. The suppressions of MAPK and NF-kappaB signaling
      pathways by sophocarpine were also found in LPS-induced RA-FLSs. The attenuation
      of the symptoms in CIA mouse model were significant, in which concentrations of
      proinflammatory cytokines were decreased after the sophocarpine treatment. In
      this study, we demonstrated the potential of sophocarpine in treating RA, both in
      vitro and in vivo. Sophocarpine may be a potential drug in treating human RA.

PMID- 29187340
TI  - Enzyme-Linked Immunosorbent Spot (ELISpot) monitoring of cytokine-producing cells
      for the prediction of acute rejection in renal transplant patients.
AB  - The purpose of this study was to evaluate T-cell immunity markers using serial
      post-transplantation monitoring of cytokine-producing cells during the first post
      transplant months for the prediction of acute rejection and potentially chronic
      rejection of kidney allograft. We followed 57 kidney allograft recipients for
      meanly 3 years post-transplantation. Blood samples were collected pre-transplant,
      2, 4 and 12 weeks post-transplant. The frequencies of IL-10-, IL-17- and IFN
      gamma-producing cells were determined in all time-points using ELISPOT assay. The
      results of ELISpot monitoring and levels of IL-23 and TGF-beta were compared
      between recipients with acute (n = 12) or chronic rejection episodes and patients
      with stable graft function (n = 45). In all post-transplant time-points,
      significantly high frequencies of IFN-gamma- and IL-17-producing cells and low
      frequency of IL-10-producing cells were observed in rejection group versus
      patients with stable graft function (P < 0.0001). The ROC curve analysis for
      determining the reliability of cytokine-producing cells for the prediction of
      acute rejection revealed that AUC was 0.046 for IL-10 (P < 0.001), 0.927 for IL
      17 (P < 0.001) and 0.929 for INF-gamma-producing cells (P < 0.001). Our results
      indicate that analyzing the frequencies of INF-gamma/IL-10/IL-17-producing cells
      may define a reliable panel for the prediction of acute rejection within the
      first post-transplant year which could also be applicable for the prediction of
      chronic rejection episodes.

PMID- 29187341
TI  - Single-access liver floss technique with antegrade hepatic vein access and
      recanalization in Budd-Chiari syndrome.
AB  - A 14-year-old boy presented with several months of increasing abdominal girth and
      fatigue. Imaging confirmed massive ascites and hepatic congestion secondary to
      central hepatic venous obstruction. Several large intrahepatic collateral veins
      were seen draining via caudate and emissary veins. After an unsuccessful attempt
      at retrograde recanalization utilizing intravascular ultrasound, the right
      hepatic vein was recanalized in an antegrade fashion by way of a prominent
      caudate collateral vein, and subsequently stented. We herein discuss the
      established treatment options for Budd-Chiari syndrome and describe our
      experience employing a single-access liver floss technique.

PMID- 29187342
TI  - Assessing the Efficacy of Mobile Health Apps Using the Basic Principles of
      Cognitive Behavioral Therapy: Systematic Review.
AB  - BACKGROUND: Cognitive behavioral therapy (CBT) in its basic principle has
      developed itself as a stand-alone, substantial method of therapy. With effective
      application in therapy for a range of mental health issues, the spread of CBT
      methods to Web-based therapy sources is evident. The development of mobile phone
      apps using CBT principles is increasing within the research area. Despite the
      move to Web-based methods of therapy, it is argued that these methods lack the
      same efficacy of face-to-face therapy sessions. OBJECTIVE: The aim of this review
      was to assess extent research findings with regard to the effectiveness of CBT
      related mobile health (mHealth) apps. By assessing only studies employing a
      randomized controlled trial design, the review aimed to determine app efficacy
      within the highly regarded method of investigation. METHODS: A comprehensive
      literature search was conducted across several databases. Search results were
      filtered, and results were subject to strict inclusion and exclusion criteria
      because of the nature of the review. Where possible, analysis of effect size was
      calculated and results reported. RESULTS: A total of 8 studies investigating the
      effectiveness of mHealth CBT-related apps across a range of mental health issues
      were reviewed. Three studies used the app against a control group, and 5 studies
      used the app intervention against another form of treatment or intervention. A
      range of effect sizes were seen across all included studies (d=-0.13 to 1.83;
      0.03-1.44), with the largest effects often being seen when comparing the data
      from pre- to posttest for the app engaged group. CONCLUSIONS: The studies
      reviewed support the use of mHealth apps containing CBT principles for a range of
      mental health issues. However, the effectiveness over longer time periods should
      be assessed. Researchers and professionals should seek to collaborate effectively
      when creating new apps to enhance their effectiveness as a treatment for the
      general public.

PMID- 29187343
TI  - An eHealth Application of Self-Reported Sports-Related Injuries and Illnesses in
      Paralympic Sport: Pilot Feasibility and Usability Study.
AB  - BACKGROUND: Sport participation is associated with a risk of sports-related
      injuries and illnesses, and Paralympic athletes' additional medical issues can be
      a challenge to health care providers and medical staff. However, few prospective
      studies have assessed sports-related injuries and illnesses in Paralympic sport
      (SRIIPS) over time. Advances in mobile phone technology and networking systems
      offer novel opportunities to develop innovative eHealth applications for
      collection of athletes' self-reports. Using eHealth applications for collection
      of self-reported SRIIPS is an unexplored area, and before initiation of full
      scale research of SRIIPS, the feasibility and usability of such an approach needs
      to be ascertained. OBJECTIVE: The aim of this study was to perform a 4-week pilot
      study and (1) evaluate the monitoring feasibility and system usability of a novel
      eHealth application for self-reported SRIIPS and (2) report preliminary data on
      SRIIPS. METHODS: An eHealth application for routine collection of data from
      athletes was developed and adapted to Paralympic athletes. A 4-week pilot study
      was performed where Paralympic athletes (n=28) were asked to weekly self-report
      sport exposure, training load, general well-being, pain, sleep, anxiety, and
      possible SRIIPS. The data collection was followed by a poststudy use assessment
      survey. Quantitative data related to the system use (eg, completed self-reports,
      missing responses, and errors) were analyzed using descriptive statistics. The
      qualitative feasibility and usability data provided by the athletes were
      condensed and categorized using thematic analysis methods. RESULTS: The weekly
      response rate was 95%. The athletes were of the opinion that the eHealth
      application was usable and feasible but stated that it was not fully adapted to
      Paralympic athletes and their impairments. For example, it was difficult to
      understand how a new injury or illness should be identified when the impairment
      was involved. More survey items related to the impairments were requested, as the
      athletes perceived that injuries and illnesses often occurred because of the
      impairment. Options for description of multifactorial incidents including an
      injury, an illness, and the impairment were also insufficient. Few technical
      issues were encountered, but athletes with visual impairment reported usability
      difficulties with the speech synthesizer. An incidence rate of 1.8 injuries and
      1.7 illnesses per 100 hours of athlete exposure were recorded. The weekly pain
      prevalence was 56% and the impairment contributed to 20% of the reported
      incidents. CONCLUSIONS: The novel eHealth-based application for self-reported
      SRIIPS developed and tested in this pilot study was generally feasible and
      usable. With some adaptation to accommodate Paralympic athletes' prerequisites
      and improved technical support for athletes with visual impairment, this
      application can be recommended for use in prospective studies of SRIIPS. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02788500;
      https://clinicaltrials.gov/ct2/show/NCT02788500 (Archived by WebCite at
      http://www.webcitation.org/6v56OqTeP).

PMID- 29187344
TI  - One Drop | Mobile on iPhone and Apple Watch: An Evaluation of HbA1c Improvement
      Associated With Tracking Self-Care.
AB  - BACKGROUND: The One Drop | Mobile app supports manual and passive (via HealthKit
      and One Drop's glucose meter) tracking of self-care and glycated hemoglobin A1c
      (HbA1c). OBJECTIVE: We assessed the HbA1c change of a sample of people with type
      1 diabetes (T1D) or type 2 diabetes (T2D) using the One Drop | Mobile app on
      iPhone and Apple Watch, and tested relationships between self-care tracking with
      the app and HbA1c change. METHODS: In June 2017, we identified people with
      diabetes using the One Drop | Mobile app on iPhone and Apple Watch who entered
      two HbA1c measurements in the app 60 to 365 days apart. We assessed the
      relationship between using the app and HbA1c change. RESULTS: Users had T1D
      (n=65) or T2D (n=191), were 22.7% (58/219) female, with diabetes for a mean 8.34
      (SD 8.79) years, and tracked a mean 2176.35 (SD 3430.23) self-care activities
      between HbA1c entries. There was a significant 1.36% or 14.9 mmol/mol HbA1c
      reduction (F=62.60, P<.001) from the first (8.72%, 71.8 mmol/mol) to second HbA1c
      (7.36%, 56.9 mmol/mol) measurement. Tracking carbohydrates was independently
      associated with greater HbA1c improvement (all P<.01). CONCLUSIONS: Using One
      Drop | Mobile on iPhone and Apple Watch may favorably impact glycemic control.

PMID- 29187345
TI  - Wide-field en face swept-source optical coherence tomography angiography using
      extended field imaging in diabetic retinopathy.
AB  - AIMS: To examine the feasibility of wide-field en face swept-source optical
      coherence tomography angiography (SS-OCTA) with extended field imaging (EFI) for
      evaluation of the retinal vasculature in diabetic retinopathy (DR). METHODS: This
      study included 37 eyes of 27 patients (age, 65+/-10 years; male patients, 18;
      female patients, 9) with DR. All patients underwent comprehensive
      ophthalmological examination, including OCTA and fluorescein angiography (FA).
      The imaging methods were compared for visible field of view, presence and extent
      of non-perfused areas (NPAs), presence and number of new blood vessels (NVs),
      vessel density (VD) and patient comfort level measured by Visual Analogue Scale.
      RESULTS: SS-OCTA with EFI allowed capture of larger areas (by 1.80+/-0.18 times
      on average) of the fundus than SS-OCTA without EFI. Compared with FA, the
      sensitivities of SS-OCTA with EFI for detection of NPAs and NVs were 96% and 79%,
      respectively, with specificities of 100% and 96%, respectively. There was no
      significant difference in extent of NPAs (61.2+/-45.8 vs 61.5+/-55.0 disc areas,
      P=0.99) or number of NVs (1.5+/-3.3 vs 0.9+/-1.8, P=0.68) between FA and SS-OCTA
      with EFI. VD showed significantly lower values in EFI SS-OCTA than in those
      acquired without EFI (31.6%+/-4.3%  vs 34.2%+/-4.3%, P<0.001). Wide-field OCTA
      with EFI was significantly more comfortable for patients than FA (P<0.001).
      CONCLUSIONS: SS-OCTA with EFI allows acquisition of wide-field en face images of
      the retinal vasculature in patients with DR, with greater patient comfort than
      FA.

PMID- 29187346
TI  - Influence of early childhood burns on school performance: an Australian
      population study.
AB  - OBJECTIVES: To determine the influence of burn injuries on childhood performance
      in national standardised curriculum-based school tests. DESIGN: Birth and health
      records of 977 children who were hospitalised with a burn injury between 2000 and
      2006 in the state of New South Wales, Australia, were linked to performance
      scores in the National Assessment Program: Literacy and Numeracy test, a
      compulsory nationwide curriculum-based test (CBT) and compared with children who
      were not hospitalised for burns and who were matched for birth year, gender,
      gestation and socioeconomic status. MAIN OUTCOME MEASURES: Test scores in years 3
      (ages 8-9), 5 (ages 10-11) and 7 (ages 13-14) in numeracy, writing, reading,
      spelling, grammar and punctuation. RESULTS: Mean age at first burn injury was 28
      months (median: 20, range: 0-140). Children with burns were significantly more
      likely to have younger mothers (28.5 vs 29.6 years) (P<0.001), be indigenous (OR
      2.5 (95% CI 2.1 to 3.1)) (P<0.001) and have siblings (OR 1.2 (95% CI 1.1 to 1.4))
      (P<0.001). They were also less likely to meet national minimum standards in most
      domains of testing until year 5, even after adjustment for parental education
      levels, parental smoking, maternal age and indigenous status. Each 10% increase
      in total body surface area burnt was associated with a decrease in year 5 scores
      by 37.0% in numeracy and 71.9% in writing. CONCLUSIONS: Most childhood burn
      injuries occur before the start of formal schooling. Children who are
      hospitalised for burns perform more poorly in CBT even after accounting for
      family and socioeconomic disadvantage. Rehabilitation of children with burn
      injuries must address school performance to decrease any long-term negative
      societal impact of burns.

PMID- 29187347
TI  - Back to blame: the Bawa-Garba case and the patient safety agenda.

PMID- 29187348
TI  - Walking: a best buy for public and planetary health.

PMID- 29187349
TI  - Isokinetic strength assessment offers limited predictive validity for detecting
      risk of future hamstring strain in sport: a systematic review and meta-analysis.
AB  - OBJECTIVE: To examine the value of isokinetic strength assessment for predicting
      risk of hamstring strain injury, and to direct future research into hamstring
      strain injuries. DESIGN: Systematic review. DATA SOURCES: Database searches for
      Medline, CINAHL, Embase, AMED, AUSPORT, SPORTDiscus, PEDro and Cochrane Library
      from inception to April 2017. Manual reference checks, ahead-of-press and
      citation tracking. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective
      studies evaluating isokinetic hamstrings, quadriceps and hip extensor strength
      testing as a risk factor for occurrence of hamstring muscle strain. METHODS:
      Independent search result screening. Risk of bias assessment by independent
      reviewers using Quality in Prognosis Studies tool. Best evidence synthesis and
      meta-analyses of standardised mean difference (SMD). RESULTS: Twelve studies were
      included, capturing 508 hamstring strain injuries in 2912 athletes. Isokinetic
      knee flexor, knee extensor and hip extensor outputs were examined at angular
      velocities ranging 30-300 degrees /s, concentric or eccentric, and relative
      (Nm/kg) or absolute (Nm) measures. Strength ratios ranged between 30 degrees /s
      and 300 degrees /s. Meta-analyses revealed a small, significant predictive effect
      for absolute (SMD=-0.16, P=0.04, 95% CI -0.31 to -0.01) and relative (SMD=-0.17,
      P=0.03, 95% CI -0.33 to -0.014) eccentric knee flexor strength (60 degrees /s).
      No other testing speed or strength ratio showed statistical association. Best
      evidence synthesis found over half of all variables had moderate or strong
      evidence for no association with future hamstring injury. SUMMARY/CONCLUSION:
      Despite an isolated finding for eccentric knee flexor strength at slow speeds,
      the role and application of isokinetic assessment for predicting hamstring strain
      risk should be reconsidered, particularly given costs and specialised training
      required.

PMID- 29187351
TI  - Viagra will be available over counter.

PMID- 29187350
TI  - Risk of losing remission, low disease activity or radiographic progression in
      case of bDMARD discontinuation or tapering in rheumatoid arthritis: systematic
      analysis of the literature and meta-analysis.
AB  - OBJECTIVES: To assess the risk of losing remission, low disease activity (LDA) or
      radiographic progression in the case of (1) discontinuing or (2) tapering doses
      of biological disease-modifying antirheumatic drugs (bDMARDs) compared with
      continuation of the initial treatment regimen in rheumatoid arthritis (RA)
      patients with remission or LDA. MATERIALS AND METHODS: A systematic literature
      analysis was carried out through May 2017 on the PubMed, Embase, Cochrane and
      international congress databases, selecting controlled trials comparing bDMARDs
      discontinuation/tapering versus continuation in RA patients with remission or
      LDA. The meta-analysis assessed the risk ratio (RR) and 95% CI of losing
      remission or LDA and the risk of radiographic progression after (1) discontinuing
      and (2) tapering doses of bDMARDs versus continuing the initial treatment.
      RESULTS: The meta-analysis comparing bDMARDs discontinuation versus continuation
      performed on nine trials showed an increased risk of losing remission (RR (95%
      CI)=1.97(1.43 to 2.73), P<0.0001) or LDA (RR (95% CI)=2.24(1.52 to 3.30),
      P<0.0001) and an increased risk of radiographic progression (RR (95%
      CI)=1.09(1.02 to 1.17), P=0.01) in case of bDMARD discontinuation. The meta
      analysis comparing bDMARDs tapering versus continuation performed on 11 trials
      showed an increased risk of losing remission (RR (95% CI)=1.23(1.06 to 1.42),
      P=0.006) but no increased risk of losing LDA (RR (95% CI)=1.02 (0.85 to 1.23),
      P=0.81) nor any increased risk of radiographic progression (RR (95% CI)=1.09(0.94
      to 1.26), P=0.26) in case of bDMARD tapering. CONCLUSION: Discontinuation of
      bDMARDs leads to an increased risk of losing remission or LDA and radiographic
      progression, while tapering doses of bDMARDs does not increase the risk of
      relapse (LDA) or radiographic progression, even though there is an increased risk
      of losing remission.

PMID- 29187352
TI  - Are disruptive innovators in GP provision strengthening or weakening the NHS?

PMID- 29187353
TI  - NHS England's handling of 102 000 lost medical records is "unacceptable," say
      MPs.

PMID- 29187354
TI  - Lactase Persistence and Body Mass Index: The Contribution of Mendelian
      Randomization.

PMID- 29187355
TI  - State of the Science in Dried Blood Spots.
AB  - BACKGROUND: Advancements in the quality and availability of highly sensitive
      analytical instrumentation and methodologies have led to increased interest in
      the use of microsamples. Among microsamples, dried blood spots (DBS) are the most
      well-known. Although there have been a variety of review papers published on DBS,
      there has been no attempt at describing the full range of analytes measurable in
      DBS, or any systematic approach published for characterizing the strengths and
      weaknesses associated with adoption of DBS analyses. CONTENT: A scoping review of
      reviews methodology was used for characterizing the state of the science in DBS.
      We identified 2018 analytes measured in DBS and found every common analytic
      method applied to traditional liquid samples had been applied to DBS samples.
      Analytes covered a broad range of biomarkers that included genes, transcripts,
      proteins, and metabolites. Strengths of DBS enable its application in most
      clinical and laboratory settings, and the removal of phlebotomy and the need for
      refrigeration have expanded biosampling to hard-to-reach and vulnerable
      populations. Weaknesses may limit adoption in the near term because DBS is a
      nontraditional sample often requiring conversion of measurements to plasma or
      serum values. Opportunities presented by novel methodologies may obviate many of
      the current limitations, but threats around the ethical use of residual samples
      must be considered by potential adopters. SUMMARY: DBS provide a wide range of
      potential applications that extend beyond the reach of traditional samples.
      Current limitations are serious but not intractable. Technological advancements
      will likely continue to minimize constraints around DBS adoption.

PMID- 29187356
TI  - Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization
      Analysis of 184802 Individuals from 25 Studies.
AB  - BACKGROUND: Associations between dairy intake and body mass index (BMI) have been
      inconsistently observed in epidemiological studies, and the causal relationship
      remains ill defined. METHODS: We performed Mendelian randomization (MR) analysis
      using an established dairy intake-associated genetic polymorphism located
      upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental
      variable (IV). Linear regression models were fitted to analyze associations
      between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c)
      rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was
      quantified by IV estimators among 184802 participants from 25 studies. RESULTS:
      Higher dairy intake was associated with higher BMI (beta = 0.03 kg/m2 per
      serving/day; 95% CI, 0.00-0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T
      allele was significantly associated with 0.20 (95% CI, 0.14-0.25) serving/day
      higher dairy intake (P = 3.15 * 10-12) and 0.12 (95% CI, 0.06-0.17) kg/m2 higher
      BMI (P = 2.11 * 10-5). MR analysis showed that the genetically determined higher
      dairy intake was significantly associated with higher BMI (beta = 0.60 kg/m2 per
      serving/day; 95% CI, 0.27-0.92; P = 3.0 * 10-4). CONCLUSIONS: The present study
      provides strong evidence to support a causal effect of higher dairy intake on
      increased BMI among adults.

PMID- 29187359
TI  - Simon Gilbody: The importance of being active.

PMID- 29187358
TI  - Vitamin D supplementation during pregnancy: state of the evidence from a
      systematic review of randomised trials.
AB  - Objectives To estimate the effects of vitamin D supplementation during pregnancy
      on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which
      trial outcome data were missing, unreported, or inconsistently reported; and to
      project the potential contributions of registered ongoing or planned
      trials.Design Systematic review and meta-analysis of randomised controlled
      trials; systematic review of registered but unpublished trials.Data sources
      Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane
      Central Register of Controlled Trials from inception to September 2017; manual
      searches of reference lists of systematic reviews identified in the electronic
      search; and online trial registries for unpublished, ongoing, or planned
      trials.Eligibility criteria for study selection Trials of prenatal vitamin D
      supplementation with randomised allocation and control groups administered
      placebo, no vitamin D, or vitamin D <=600 IU/day (or its equivalent), and
      published in a peer reviewed journal.Results 43 trials (8406 participants) were
      eligible for meta-analyses. Median sample size was 133 participants. Vitamin D
      increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose
      response effect was weak. Maternal clinical outcomes were rarely ascertained or
      reported, but available data did not provide evidence of benefits. Overall,
      vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g
      to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age
      births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven
      comparisons), but findings were not robust in sensitivity and subgroup analyses.
      There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There
      was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze
      by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta
      analyses included data from a minority of trials. Only eight of 43 trials (19%)
      had an overall low risk of bias. Thirty five planned/ongoing randomised
      controlled trials could contribute 12 530 additional participants to future
      reviews.Conclusions Most trials on prenatal vitamin D published by September 2017
      were small and of low quality. The evidence to date seems insufficient to guide
      clinical or policy recommendations. Future trials should be designed and powered
      to examine clinical endpoints, including maternal conditions related to pregnancy
      (such as pre-eclampsia), infant growth, and respiratory outcomes.Systematic
      review registration PROSPERO CRD42016051292.

PMID- 29187360
TI  - The NHS must act on bevacizumab, for patients' sake.

PMID- 29187357
TI  - IAP Antagonists Enhance Cytokine Production from Mouse and Human iNKT Cells.
AB  - Inhibitor of apoptosis protein (IAP) antagonists are in clinical trials for a
      variety of cancers, and mouse models show synergism between IAP antagonists and
      anti-PD-1 immunotherapy. Although IAP antagonists affect the intrinsic signaling
      of tumor cells, their most pronounced effects are on immune cells and the
      generation of antitumor immunity. Here, we examined the effects of IAP antagonism
      on T-cell development using mouse fetal thymic organ culture and observed a
      selective loss of iNKT cells, an effector cell type of potential importance for
      cancer immunotherapy. Thymic iNKT-cell development probably failed due to
      increased strength of TCR signal leading to negative selection, given that mature
      iNKT cells treated with IAP antagonists were not depleted, but had enhanced
      cytokine production in both mouse and human ex vivo cultures. Consistent with
      this, mature mouse primary iNKT cells and iNKT hybridomas increased production of
      effector cytokines in the presence of IAP antagonists. In vivo administration of
      IAP antagonists and alpha-GalCer resulted in increased IFNgamma and IL-2
      production from iNKT cells and decreased tumor burden in a mouse model of
      melanoma lung metastasis. Human iNKT cells also proliferated and increased
      IFNgamma production dramatically in the presence of IAP antagonists,
      demonstrating the utility of these compounds in adoptive therapy of iNKT cells.
      Cancer Immunol Res; 6(1); 25-35. (c)2017 AACR.

PMID- 29187361
TI  - Diet-dependence of metabolic perturbations mediated by the endocrine disruptor
      tolylfluanid.
AB  - Emerging evidence implicates environmental endocrine-disrupting chemicals (EDCs)
      in the pathogenesis of metabolic diseases such as obesity and diabetes; however,
      the interactions between EDCs and traditional risk factors in disease
      pathogenesis remain incompletely characterized. The present study interrogates
      the interaction of the EDC tolylfluanid (TF) and traditional dietary stressors in
      the promotion of metabolic dysfunction. Eight-week-old male C57BL/6 mice were fed
      a high-fat, high-sucrose diet (HFHSD) or a high-sucrose diet (HSD), with or
      without TF supplementation at 100 MUg/g, for 12 weeks. Food intake, body weight
      and visceral adiposity were quantified. Glucose homeostasis was interrogated by
      intraperitoneal glucose and insulin tolerance tests at 9 and 10 weeks of
      exposure, respectively. After 12 weeks of dietary exposure, metabolic cage
      analyses were performed to interrogate nutrient handling and energy expenditure.
      In the background of an HFHSD, TF promoted glucose intolerance; however, weight
      gain and insulin sensitivity were unchanged, and visceral adiposity was reduced.
      In the background of an HSD, TF increased visceral adiposity; however, glucose
      tolerance and insulin sensitivity were unchanged, while weight gain was reduced.
      Thus, these analyses reveal that the metabolic perturbations induced by dietary
      exposure to TF, including the directionality of alterations in body weight gain,
      visceral adiposity and glucose homeostasis, are influenced by dietary
      macronutrient composition, suggesting that populations may exhibit distinct
      metabolic risks based on their unique dietary characteristics.

PMID- 29187363
TI  - TRPV4 heats up ANO1-dependent exocrine gland fluid secretion.
AB  - Several ion channels and transporters regulate fluid secretion in salivary and
      lacrimal glands. In salivary glands, the major anion channel involved in fluid
      secretion is the calcium-activated chloride channel anoctamin 1 (ANO1). Several
      members of the transient receptor potential (TRP) channel superfamily regulate
      ANO1 activity. Here, we report a functional interaction between thermosensitive
      TRP vanilloid (TRPV)4 and ANO1 in acinar cells isolated from mouse salivary and
      lacrimal glands. TRPV4 activation induced chloride currents and shrinkage of
      acinar cells by increasing intracellular calcium concentrations. The chloride
      currents evoked by a TRPV4-specific activator (GSK1016790A) were identified as
      ANO1-mediated currents. Moreover, TRPV4 activation by an inositol 1,4,5
      trisphosphate (IP3)-dependent mechanism was found to contribute to the muscarinic
      pathway of fluid secretion. Muscarinic stimulation of saliva and tear secretion
      was down-regulated in both TRPV4-deficient mice and in acinar cells treated with
      a TRPV4-specific antagonist (HC-067047). Furthermore, the temperature dependence
      of muscarinic salivation was shown to depend mainly on TRPV4. Our results suggest
      that TRPV4 interacts with IP3 receptors and ANO1 to regulate the muscarinic
      pathway that mediates salivation and lacrimation.-Derouiche, S., Takayama, Y.,
      Murakami, M., Tominaga, M. TRPV4 heats up ANO1-dependent exocrine gland fluid
      secretion.

PMID- 29187362
TI  - IKK2/NF-kappaB signaling protects neurons after traumatic brain injury.
AB  - Traumatic brain injury (TBI) is the leading cause of death in young adults. After
      the initial injury, a poorly understood secondary phase, including a strong
      inflammatory response determines the final outcome of TBI. The inhibitor of NF
      kappaB kinase (IKK)/NF-kappaB signaling system is the key regulator of
      inflammation and also critically involved in regulation of neuronal survival and
      synaptic plasticity. We addressed the neuron-specific function of IKK2/NF-kappaB
      signaling pathway in TBI using an experimental model of closed-head injury (CHI)
      in combination with mouse models allowing conditional regulation of IKK/NF-kappaB
      signaling in excitatory forebrain neurons. We found that repression of IKK2/NF
      kappaB signaling in neurons increases the acute posttraumatic mortality rate,
      worsens the neurological outcome, and promotes neuronal cell death by apoptosis,
      thus resulting in enhanced proinflammatory gene expression. As a potential
      mechanism, we identified elevated levels of the proapoptotic mediators Bax and
      Bad and enhanced expression of stress response genes. This phenotype is also
      observed when neuronal IKK/NF-kappaB activity is inhibited just before CHI. In
      contrast, neuron-specific activation of IKK/NF-kappaB signaling does not alter
      the TBI outcome. Thus, this study demonstrates that physiological neuronal IKK/NF
      kappaB signaling is necessary and sufficient to protect neurons from trauma
      consequences.-Mettang, M., Reichel, S. N., Lattke, M., Palmer, A., Abaei, A.,
      Rasche, V., Huber-Lang, M., Baumann, B., Wirth, T. IKK2/NF-kappaB signaling
      protects neurons after traumatic brain injury.

PMID- 29187364
TI  - Characterization of CD38 in the major cell types of the heart: endothelial cells
      highly express CD38 with activation by hypoxia-reoxygenation triggering NAD(P)H
      depletion.
AB  - The NAD(P)+-hydrolyzing enzyme CD38 is activated in the heart during the process
      of ischemia and reperfusion, triggering NAD(P)(H) depletion. However, the
      presence and role of CD38 in the major cell types of the heart are unknown.
      Therefore, we characterize the presence and function of CD38 in cardiac myocytes,
      endothelial cells, and fibroblasts. To comprehensively evaluate CD38 in these
      cells, we measured gene transcription via mRNA, as well as protein expression and
      enzymatic activity. Endothelial cells strongly expressed CD38, while only low
      expression was present in cardiac myocytes with intermediate levels in
      fibroblasts. In view of this high level expression in endothelial cells and the
      proposed role of CD38 in the pathogenesis of endothelial dysfunction, endothelial
      cells were subjected to hypoxia-reoxygenation to characterize the effect of this
      stress on CD38 expression and activity. An activity-based CD38 imaging method and
      CD38 activity assays were used to characterize CD38 activity in normoxic and
      hypoxic-reoxygenated endothelial cells, with marked CD38 activation seen
      following hypoxia-reoxygenation. To test the impact of hypoxia-reoxygenation
      induced CD38 activation on endothelial cells, NAD(P)(H) levels and endothelial
      nitric oxide synthase (eNOS)-derived NO production were measured. Marked NADP(H)
      depletion with loss of NO and increase in superoxide production occurred
      following hypoxia-reoxygenation that was prevented by CD38 inhibition or
      knockdown. Thus, endothelial cells have high expression of CD38 which is
      activated by hypoxia-reoxygenation triggering CD38-mediated NADP(H) depletion
      with loss of eNOS-mediated NO generation and increased eNOS uncoupling. This
      demonstrates the importance of CD38 in the endothelium and explains the basis by
      which CD38 triggers post-ischemic endothelial dysfunction.

PMID- 29187365
TI  - Foxo1 nucleo-cytoplasmic distribution and unidirectional nuclear influx are the
      same in nuclei in a single skeletal muscle fiber but vary between fibers.
AB  - Foxo transcription factors promote protein breakdown and atrophy of skeletal
      muscle fibers. Foxo transcriptional effectiveness is largely determined by
      phosphorylation-dependent nucleo-cytoplasmic shuttling. Imaging Foxo1-green
      fluorescent protein (GFP) over time in 124 nuclei in 68 multinucleated adult
      skeletal muscle fibers under control culture conditions reveals large variability
      between fibers in Foxo1-GFP nucleo-cytoplasmic concentration ratio (N/C) and in
      the apparent rate coefficient ( kI') for Foxo1-GFP unidirectional nuclear influx
      (measured with efflux blocked by leptomycin B). Pairs of values of N/C or of kI'
      from different nuclei in the same fiber were essentially the same, but only
      weakly correlated in nuclei from different fibers in the same culture well. Thus,
      fiber to fiber variability of cellular factors, but not extracellular factors,
      determines Foxo1 distribution. Over all nuclei, N/C and kI' were closely
      proportional, indicating that kI' is the major determinant of Foxo1 distribution.
      IGF-I activation of Foxo kinase Akt reduces variability by decreasing kI' and N/C
      in all fibers. However, inhibiting Akt did not drive kI' uniformly high,
      indicating other pathways in Foxo1 regulation.

PMID- 29187366
TI  - Cell confluence regulates claudin-2 expression: possible role for ZO-1 and Rac.
AB  - Claudin-2 (Cldn-2) is a channel-forming tight junction (TJ) protein in the
      proximal tubules that mediates paracellular Na+ transport and has also emerged as
      a regulator of proliferation and migration. Expression of Cldn-2 is altered by
      numerous stimuli, but the underlying mechanisms remain incompletely understood.
      Here we show that Cldn-2 protein and mRNA expression were low in subconfluent
      tubular cells and increased during junction maturation. Cldn-1 or occludin did
      not exhibit similar confluence-dependence. Conversely, disruption of TJs by Ca2+
      removal or silencing of zonula occludens-1 (ZO-1) or ZO-2 induced a large drop in
      Cldn-2 abundance. Immunofluorescent staining revealed a more uneven Cldn-2
      staining in nascent, Cldn-1-positive TJs. Subconfluence and ZO-1 silencing
      augmented Cldn-2 degradation and reduced Cldn-2 promoter activity, suggesting
      that insertion into the TJs slows Cldn-2 turnover. Indeed, blocking endocytosis
      or lysosomal degradation increased Cldn-2 abundance. Cell confluence increased
      expression of the junctional adapters ZO-1 and -2, and the small GTPase Rac, and
      elevated Rac activity and p21-activated kinase (Pak) phosphorylation, suggesting
      that they might mediate confluence-dependent Cldn-2 regulation. Indeed, Rac
      silencing or Pak inhibition strongly reduced Cldn-2 protein abundance, which was
      likely the combined effect on turnover, as these interventions reduced Cldn-2
      promoter activity and augmented Cldn-2 degradation. Taken together, our data
      suggest that TJ integrity and maturity, ZO-1 expression/TJ localization, and
      Rac/Pak control Cldn-2 degradation and synthesis. A feedback mechanism connecting
      Cldn-2 expression with junction remodeling, e.g., during wound healing,
      epithelial-mesenchymal transition, or tumor metastasis formation, may have
      important downstream effects on permeability, proliferation, and migration.

PMID- 29187367
TI  - Oxidative stress increases megalin expression in the renal proximal tubules
      during the normoalbuminuric stage of diabetes mellitus.
AB  - Megalin, an endocytic receptor expressed in proximal tubule cells, plays a
      critical role in renal tubular protein reabsorption and is associated with the
      albuminuria observed in diabetic nephropathy. We have previously reported
      increased oxidant production in the renal cortex during the normoalbuminuric
      stage of diabetes mellitus (DM); however, the relationship between oxidative
      stress and renal megalin expression during the normoalbuminuric stage of DM
      remains unclear. In the present study, we evaluated whether oxidative stress
      affects megalin expression in the normoalbuminuric stage of DM in a
      streptozotocin-induced diabetic rat model and in immortalized human proximal
      tubular cells (HK-2). We demonstrated that increased expression of renal megalin
      accompanies oxidative stress during the early stage of DM, before albuminuria
      development. Telmisartan treatment prevented the diabetes-induced elevation in
      megalin level, possibly through an oxidative stress-dependent mechanism. In HK-2
      cells, hydrogen peroxide significantly increased megalin levels in a dose- and
      time-dependent manner; however, the elevation in megalin expression was decreased
      following prolonged exposure to severe oxidative stress induced by 0.4 mmol/l
      hydrogen peroxide. High-glucose treatment also significantly increased megalin
      expression in HK-2 cells. Concurrent administration of the antioxidant N-acetyl
      cysteine blocked the effects of high glucose on megalin expression. Furthermore,
      the hydrogen peroxide-induced increase in megalin expression was blocked by
      treatment with phosphatidylinositol 3-kinase and Akt inhibitors. Increase of
      phosphorylated Akt expression was also seen in the renal cortex of diabetic rats.
      Taken together, our results indicate that mild oxidative stress increases renal
      megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the
      normoalbuminuric stage of DM.

PMID- 29187370
TI  - Ste20-like kinase, SLK, a novel mediator of podocyte integrity.
AB  - SLK is essential for embryonic development and may play a key role in wound
      healing, tumor growth, and metastasis. Expression and activation of SLK are
      increased in kidney development and during recovery from ischemic acute kidney
      injury. Overexpression of SLK in glomerular epithelial cells/podocytes in vivo
      induces injury and proteinuria. Conversely, reduced SLK expression leads to
      abnormalities in cell adhesion, spreading, and motility. Tight regulation of SLK
      expression thus may be critical for normal renal structure and function. We
      produced podocyte-specific SLK-knockout mice to address the functional role of
      SLK in podocytes. Mice with podocyte-specific deletion of SLK showed reduced
      glomerular SLK expression and activity compared with control. Podocyte-specific
      deletion of SLK resulted in albuminuria at 4-5 mo of age in male mice and 8-9 mo
      in female mice, which persisted for up to 13 mo. At 11-12 mo, knockout mice
      showed ultrastructural changes, including focal foot process effacement and
      microvillous transformation of podocyte plasma membranes. Mean foot process width
      was approximately twofold greater in knockout mice compared with control.
      Podocyte number was reduced by 35% in knockout mice compared with control, and
      expression of nephrin, synaptopodin, and podocalyxin was reduced in knockout mice
      by 20-30%. In summary, podocyte-specific deletion of SLK leads to albuminuria,
      loss of podocytes, and morphological evidence of podocyte injury. Thus, SLK is
      essential to the maintenance of podocyte integrity as mice age.

PMID- 29187368
TI  - N-linked glycans are required on epithelial Na+ channel subunits for maturation
      and surface expression.
AB  - Epithelial Na+ channel (ENaC) subunits undergo N-linked glycosylation in the
      endoplasmic reticulum where they assemble into an alphabetagamma complex. Six,
      13, and 5 consensus sites (Asn-X-Ser/Thr) for N-glycosylation reside in the
      extracellular domains of the mouse alpha-, beta-, and gamma-subunits,
      respectively. Because the importance of ENaC N-linked glycans has not been fully
      addressed, we examined the effect of preventing N-glycosylation of specific
      subunits on channel function, expression, maturation, and folding. Heterologous
      expression in Xenopus oocytes or Fischer rat thyroid cells with alphabetagamma
      ENaC lacking N-linked glycans on a single subunit reduced ENaC activity as well
      as the inhibitory response to extracellular Na+. The lack of N-linked glycans on
      the beta-subunit also precluded channel activation by trypsin. However, channel
      activation by shear stress was N-linked glycan independent, regardless of which
      subunit was modified. We also discovered that the lack of N-linked glycans on any
      one subunit reduced the total and surface levels of cognate subunits. The lack of
      N-linked glycans on the beta-subunit had the largest effect on total levels, with
      the lack of N-linked glycans on the gamma- and alpha-subunits having intermediate
      and modest effects, respectively. Finally, channels with wild-type beta-subunits
      were more sensitive to limited trypsin proteolysis than channels lacking N-linked
      glycans on the beta-subunit. Our results indicate that N-linked glycans on each
      subunit are required for proper folding, maturation, surface expression, and
      function of the channel.

PMID- 29187369
TI  - Pharmacological and genetic inhibition of downstream targets of p38 MAPK in
      experimental nephrotic syndrome.
AB  - Nie X, Chanley MA, Pengal R, Thomas DB, Agrawal S, Smoyer WE. Pharmacological and
      genetic inhibition of downstream targets of p38 MAPK in experimental nephrotic
      syndrome. Am J Physiol Renal Physiol 314: F602-F613, 2018. First published
      November 29, 2017; doi: 10.1152/ajprenal.00207.2017 .-The p38 MAPK pathway plays
      a crucial role in various glomerulopathies, with activation being associated with
      disease and inhibition being associated with disease amelioration. We
      hypothesized that the downstream targets of p38 MAPK, MAPK-activated protein
      kinase 2 and/or 3 (MK2 and/or MK3), play an important role in mediating injury in
      experimental nephrotic syndrome via their actions on their downstream substrates
      heat shock protein B1 (HSPB1) and cyclooxygenase-2 (COX-2). To test this
      hypothesis, the effects of both pharmacological and genetic inhibition of MK2 and
      MK3 were examined in mouse adriamycin (ADR) and rat puromycin aminonucleoside
      (PAN) nephropathy models. MK2-/-, MK3-/-, and MK2-/-MK3-/- mice were generated in
      the Sv129 background and subjected to ADR-induced nephropathy. MK2 and MK3
      protein expression was completely abrogated in the respective knockout genotypes,
      and massive proteinuria and renal histopathological changes developed after ADR
      treatment. Furthermore, renal cortical HSPB1 was induced in all four genotypes by
      day 21, but HSPB1 was activated only in the wild-type and MK3-/- mice. Expression
      of the stress proteins HSPB8 and glucose-regulated protein 78 (GRP78) remained
      unaltered across all genotypes. Finally, while MK2 and/or MK3-knockout
      downregulated the proinflammatory enzyme COX-2, ADR significantly induced renal
      cortical COX-2 only in MK2-/- mice. Additionally, pharmacological MK2 inhibition
      with PF-318 during PAN-induced nephropathy did not result in significant
      proteinuria reduction in rats. Together, these data suggest that while the
      inhibition of MK2 and/or MK3 regulates the renal stress response, our currently
      available approaches are not yet able to safely and effectively reduce
      proteinuria in experimental nephrotic syndrome and that other p38MAPK downstream
      targets should also be considered to improve the future treatment of glomerular
      disease.

PMID- 29187371
TI  - Effects of erythropoietin receptor activity on angiogenesis, tubular injury, and
      fibrosis in acute kidney injury: a "U-shaped" relationship.
AB  - The erythropoietin receptor (EpoR) is widely expressed but its renoprotective
      action is unexplored. To examine the role of EpoR in vivo in the kidney, we
      induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different
      EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knockin of wild
      type human EpoR, which is hypofunctional relative to murine EpoR, and a renal
      tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower
      autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal
      function and structural damage, more apoptosis at the acute stage (<7 days), and
      slower recovery with more tubulointerstitial fibrosis at the subacute stage (14
      days). In contrast, mice with hyperactive EpoR signaling from knockin of a
      constitutively active human EpoR had higher autophagic flux, milder kidney
      damage, and better renal function at the acute stage but, surprisingly, worse
      tubulointerstitial fibrosis and renal function at the subacute stage. Either
      excess or deficient EpoR activity in the kidney was associated with abnormal
      peritubular capillaries and tubular hypoxia, creating a "U-shaped" relationship.
      The direct effects of EpoR on tubular cells were confirmed in vitro by a hydrogen
      peroxide model using primary cultured proximal tubule cells with different EpoR
      activities. In summary, normal erythropoietin (EPO)/EpoR signaling in renal
      tubules provides defense against renal tubular injury maintains the autophagy
      apoptosis balance and peritubular capillary integrity. High and low EPO/EpoR
      bioactivities both lead to vascular defect, and high EpoR activity overides the
      tubular protective effects in AKI recovery.

PMID- 29187372
TI  - Renal tubular ACE-mediated tubular injury is the major contributor to
      microalbuminuria in early diabetic nephropathy.
AB  - Diabetic nephropathy is a major cause of end-stage renal disease in developed
      countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat
      diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is
      uncertain. Here, two mouse models with different patterns of renal ACE expression
      were studied to determine the specific contribution of tubular vs. glomerular ACE
      to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack
      ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack
      endothelial ACE and only express renal ACE in tubular epithelial cells. The
      absence of endothelial ACE normalized the glomerular filtration rate and
      endothelial injury in diabetic ACE 3/9 mice. However, these mice developed
      tubular injury and albuminuria and displayed low renal levels of megalin that
      were similar to those observed in diabetic wild-type mice. In diabetic it-ACE
      mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced
      tubulointerstitial injury and albuminuria and increased renal megalin expression
      compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings
      demonstrate that endothelial ACE is a central regulator of the glomerular
      filtration rate while tubular ACE is a key player in the development of tubular
      injury and albuminuria. These data suggest that tubular injury, rather than
      hyperfiltration, is the main cause of microalbuminuria in early diabetic
      nephropathy.

PMID- 29187374
TI  - Corrigendum.

PMID- 29187373
TI  - Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral
      obstruction despite no upregulation of Klotho biosynthesis in the contralateral
      kidney.
AB  - In a new paradigm of etiology related to chronic kidney disease-mineral and bone
      disorder (CKD-MBD), kidney injury may cause induction of factors in the injured
      kidney that are released into the circulation and thereby initiate and maintain
      renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and
      CKD-MBD, while activin A might have detrimental effects. The unilateral ureter
      obstruction (UUO) model is used here to examine this concept by investigating
      early changes related to renal fibrosis in the obstructed kidney, untouched
      contralateral kidney, and vasculature which might be affected by secreted factors
      from the obstructed kidney, and comparing with unilateral nephrectomized controls
      (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas
      plasma Klotho increased in both UUO and UNX rats, indicating an altered
      metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of
      Klotho and maintained normal expression of the examined fibrosis-related genes,
      as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor
      beta and induction of periostin and activin A in obstructed kidneys without
      changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after
      10 days while no changes were seen in UNX rats, suggesting secretion of activin A
      from the obstructed kidney with potentially systemic effects on CKD-MBD. As such,
      increased aortic sclerostin was observed in UUO rats compared with UNX and normal
      controls. The present results are in line with the new paradigm and show very
      early vascular effects of unilateral kidney fibrosis, supporting the existence of
      a new kidney-vasculature axis.

PMID- 29187375
TI  - Advances in the diagnosis and treatment of Von Willebrand disease.
AB  - Von Willebrand disease (VWD) is the most common inherited bleeding disorder, yet
      diagnosis and management remain challenging. Development and use of bleeding
      assessment tools allows for improved stratification of which patients may require
      further assessment and which patients are most likely to require treatment of
      their VWD. New options for laboratory assessment of von Willebrand factor (VWF)
      activity include a new platelet-binding assay, the VWF:GPIbM, which is subject to
      less variability than the ristocetin cofactor activity assay, and collagen
      binding assays that provide insight into a different function of VWF. Genetic
      testing may be helpful in some cases where a type 2 VWD variant is suspected but
      is usually not helpful in type 1 VWD. Finally, treatment options for VWD are
      reviewed, including the use of recombinant VWF. Despite these advances, still
      more work is required to improve diagnosis, treatment, and quality of life for
      affected patients.

PMID- 29187378
TI  - Platelet glycoprotein VI aids in local immunity during pneumonia-derived sepsis
      caused by gram-negative bacteria.
AB  - Platelet collagen receptor glycoprotein VI (GPVI) and podoplanin receptor C-type
      lectin-like receptor 2 (CLEC2) are receptors implicated in platelet activation
      that both signal via an immunoreceptor tyrosine-based activation motif. Platelets
      are necessary for host defense and prevention of hemorrhage during sepsis, but
      the role of platelet GPVI and CLEC2 herein is unknown. To investigate this, we
      infected mice depleted of platelet GPVI or CLEC2 by antibody treatment or GPVI-/-
      mice with the common human sepsis pathogen Klebsiella pneumoniae via the airways
      to induce pneumonia-derived sepsis. The GPVI ligand collagen and the CLEC2 ligand
      podoplanin were constitutively present in the lung, whereas the GPVI ligands
      fibrin and histone were induced during pneumonia. During late-stage infection,
      both mice depleted of GPVI and GPVI-/- mice showed increased bacterial growth in
      lungs, and GPVI-/- mice also showed increased bacterial growth in distant body
      sites. Despite higher bacterial loads, GPVI-depleted mice showed reduced platelet
      numbers, platelet activation, and platelet-leukocyte complex formation in the
      bronchoalveolar space. Consistently, in human whole blood, GPVI stimulation of
      platelets increased platelet-leukocyte complex formation and leukocyte
      activation, which was accompanied by enhanced phagocytosis of Klebsiella GPVI
      depleted mice showed increased lung hemorrhage during infection, but not to the
      extent observed in platelet-depleted mice, and lung bleeding was not
      significantly different between GPVI-/- and wild-type mice. CLEC2 depletion did
      not affect any of the responses during pneumonia. These results suggest that
      platelet GPVI, but not CLEC2, contributes to local host defense during pneumonia
      derived sepsis by enhancing leukocyte function.

PMID- 29187377
TI  - A novel irreversible FLT3 inhibitor, FF-10101, shows excellent efficacy against
      AML cells with FLT3 mutations.
AB  - An activating mutation of Fms-like tyrosine kinase 3 (FLT3) is the most frequent
      genetic alteration associated with poor prognosis in acute myeloid leukemia
      (AML). Although many FLT3 inhibitors have been clinically developed, no first
      generation inhibitors have demonstrated clinical efficacy by monotherapy, due to
      poor pharmacokinetics or unfavorable safety profiles possibly associated with low
      selectivity against FLT3 kinase. Recently, a selective FLT3 inhibitor,
      quizartinib, demonstrated favorable outcomes in clinical studies. However,
      several resistant mutations emerged during the disease progression. To overcome
      these problems, we developed a novel FLT3 inhibitor, FF-10101, designed to
      possess selective and irreversible FLT3 inhibition. The co-crystal structure of
      FLT3 protein bound to FF-10101 revealed the formation of a covalent bond between
      FF-10101 and the cysteine residue at 695 of FLT3. The unique binding brought high
      selectivity and inhibitory activity against FLT3 kinase. FF-10101 showed potent
      growth inhibitory effects on human AML cell lines harboring FLT3 internal tandem
      duplication (FLT3-ITD), MOLM-13, MOLM-14, and MV4-11, and all tested types of
      mutant FLT3-expressing 32D cells including quizartinib-resistant mutations at
      D835, Y842, and F691 residues in the FLT3 kinase domain. In mouse subcutaneous
      implantation models, orally administered FF-10101 showed significant growth
      inhibitory effect on FLT3-ITD-D835Y- and FLT3-ITD-F691L-expressing 32D cells.
      Furthermore, FF-10101 potently inhibited growth of primary AML cells harboring
      either FLT3-ITD or FLT3-D835 mutation in vitro and in vivo. These results
      indicate that FF-10101 is a promising agent for the treatment of patients with
      AML with FLT3 mutations, including the activation loop mutations clinically
      identified as quizartinib-resistant mutations.

PMID- 29187376
TI  - Targeting novel mechanisms of pain in sickle cell disease.
AB  - Patients with sickle cell disease (SCD) suffer from intense pain that can start
      during infancy and increase in severity throughout life, leading to
      hospitalization and poor quality of life. A unique feature of SCD is vaso
      occlusive crises (VOCs) characterized by episodic, recurrent, and unpredictable
      episodes of acute pain. Microvascular obstruction during a VOC leads to impaired
      oxygen supply to the periphery and ischemia reperfusion injury, inflammation,
      oxidative stress, and endothelial dysfunction, all of which may perpetuate a
      noxious microenvironment leading to pain. In addition to episodic acute pain,
      patients with SCD also report chronic pain. Current treatment of moderate to
      severe pain in SCD is mostly reliant upon opioids; however, long-term use of
      opioids is associated with multiple side effects. This review presents up-to-date
      developments in our understanding of the pathobiology of pain in SCD. To help
      focus future research efforts, major gaps in knowledge are identified regarding
      how sickle pathobiology evokes pain, pathways specific to chronic and acute
      sickle pain, perception-based targets of "top-down" mechanisms originating from
      the brain and neuromodulation, and how pain affects the sickle microenvironment
      and pathophysiology. This review also describes mechanism-based targets that may
      help develop novel therapeutic and/or preventive strategies to ameliorate pain in
      SCD.

PMID- 29187379
TI  - Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of
      secondary JAK3 mutations in T-ALL.
AB  - The Janus kinase 3 (JAK3) tyrosine kinase is mutated in 10% to 16% of T-cell
      acute lymphoblastic leukemia (T-ALL) cases. JAK3 mutants induce constitutive
      JAK/STAT signaling and cause leukemia when expressed in the bone marrow cells of
      mice. Surprisingly, we observed that one third of JAK3-mutant T-ALL cases harbor
      2 JAK3 mutations, some of which are monoallelic and others that are biallelic.
      Our data suggest that wild-type JAK3 competes with mutant JAK3 (M511I) for
      binding to the common gamma chain and thereby suppresses its oncogenic potential.
      We demonstrate that JAK3 (M511I) can increase its limited oncogenic potential
      through the acquisition of an additional mutation in the mutant JAK3 allele.
      These double JAK3 mutants show increased STAT5 activation and increased potential
      to transform primary mouse pro-T cells to interleukin-7-independent growth and
      were not affected by wild-type JAK3 expression. These data extend our insight
      into the oncogenic properties of JAK3 mutations and provide an explanation of why
      progression of JAK3-mutant T-ALL cases can be associated with the accumulation of
      additional JAK3 mutations.

PMID- 29187380
TI  - Nbeal2 interacts with Dock7, Sec16a, and Vac14.
AB  - Mutations in NBEAL2, the gene encoding the scaffolding protein Nbeal2, are causal
      of gray platelet syndrome (GPS), a rare recessive bleeding disorder characterized
      by platelets lacking alpha-granules and progressive marrow fibrosis. We present
      here the interactome of Nbeal2 with additional validation by reverse
      immunoprecipitation of Dock7, Sec16a, and Vac14 as interactors of Nbeal2. We show
      that GPS-causing mutations in its BEACH domain have profound and possible effects
      on the interaction with Dock7 and Vac14, respectively. Proximity ligation assays
      show that these 2 proteins are physically proximal to Nbeal2 in human
      megakaryocytes. In addition, we demonstrate that Nbeal2 is primarily localized in
      the cytoplasm and Dock7 on the membrane of or in alpha-granules. Interestingly,
      platelets from GPS cases and Nbeal2-/- mice are almost devoid of Dock7, resulting
      in a profound dysregulation of its signaling pathway, leading to defective actin
      polymerization, platelet activation, and shape change. This study shows for the
      first time proteins interacting with Nbeal2 and points to the dysregulation of
      the canonical signaling pathway of Dock7 as a possible cause of the aberrant
      formation of platelets in GPS cases and Nbeal2-deficient mice.

PMID- 29187381
TI  - CRRL269: a novel designer and renal-enhancing pGC-A peptide activator.
AB  - The natriuretic peptides (NPs) B-type NP (BNP) and urodilatin (URO) exert renal
      protective properties via the particulate guanylyl cyclase A receptor (pGC-A). As
      a potential renal-enhancing strategy, we engineered a novel designer peptide that
      we call CRRL269. CRRL269 was investigated in human cell lines and in normal
      canines to define potential cardiorenal enhancing actions. The mechanism of its
      cardiorenal selective properties was also investigated. In vitro NP receptor
      activity was quantified with guanosine 3',5'-cyclic monophosphate generation. In
      vivo effects were determined in normal canine acute infusion studies. We observed
      that CRRL269 demonstrated enhanced pGC-A activity in renal compared with nonrenal
      cell lines. CRRL269 exerted enhanced resistance to neprilysin compared with URO.
      Importantly, CRRL269 exhibited significant and greater increases in urinary
      sodium excretion and diuresis, with less blood pressure reduction, than BNP or
      URO in normal canines. CRRL269 retained potent renin-angiotensin-aldosterone
      system (RAAS) suppressing properties shared by URO and BNP. Also, CRRL269 exerted
      less arterial relaxation and higher cAMP cardiomyocytes generation than BNP.
      CRRL269 possessed superior renal and pGC-A activating properties compared with
      BNP or URO in vitro. CRRL269 exerted enhanced renal actions while suppressing
      RAAS in vivo and with less hypotension compared with URO or BNP. Together, our
      study suggests that CRRL269 is a promising innovative renal-enhancing drug, with
      favorable protective actions targeting cardiorenal disease states through the pGC
      A receptor.

PMID- 29187383
TI  - Mice lacking PKC-theta in skeletal muscle have reduced intramyocellular lipid
      accumulation and increased insulin responsiveness in skeletal muscle.
AB  - Protein kinase C-theta (PKC-theta) is a lipid-sensitive molecule associated with
      lipid-induced insulin resistance in skeletal muscle. Rodent models have not
      cohesively supported that PKC-theta impairs insulin responsiveness in skeletal
      muscle. The purpose of this study was to generate mice that lack PKC-theta in
      skeletal muscle and determine how lipid accumulation and insulin responsiveness
      are affected in that tissue. Mice lacking PKC-theta in skeletal muscle
      (SkMPKCthetaKO) and controls (SkMPKCthetaWT) were placed on a regular diet (RD)
      or high-fat diet (HFD) for 15 wk, followed by determination of food intake,
      fasting glucose levels, lipid accumulation, and insulin responsiveness. There
      were no differences between SkMPKCthetaWT and SkMPKCthetaKO mice on a RD.
      SkMPKCthetaKO mice on a HFD gained less weight from 10 through 15 wk of dietary
      intervention ( P < 0.05). This was likely due to less caloric consumption ( P =
      0.0183) and fewer calories from fat ( P < 0.001) compared with SkMPKCthetaWT mice
      on a HFD. Intramyocellular lipid accumulation ( P < 0.0001), fatty acid binding
      protein 4, and TNF-alpha mRNA levels ( P < 0.05) were markedly reduced in
      SkMPKCthetaKO compared with SkMPKCthetaWT mice on a HFD. As a result, fasting
      hyperglycemia was mitigated and insulin responsiveness, as indicated by Akt
      phosphorylation, was maintained in SkMPKCthetaKO on a HFD. Liver lipid
      accumulation was not affected by genotype, suggesting the deletion of PKC-theta
      from skeletal muscle has a tissue-specific effect. PKC-theta is a regulator of
      lipid-induced insulin resistance in skeletal muscle. However, the effects of this
      mutation may be tissue specific. Further work is warranted to comprehensively
      evaluated whole body metabolic responses in this model.

PMID- 29187382
TI  - Opposing effects of bronchopulmonary C-fiber subtypes on cough in guinea pigs.
AB  - We have addressed the hypothesis that the opposing effects of bronchopulmonary C
      fiber activation on cough are attributable to the activation of C-fiber subtypes.
      Coughing was evoked in anesthetized guinea pigs by citric acid (0.001-2 M)
      applied topically in 100-ul aliquots to the tracheal mucosa. In control
      preparations, citric acid evoked 10 +/- 1 coughs cumulatively. Selective
      activation of the pulmonary C fibers arising from the nodose ganglia with either
      aerosols or continuous intravenous infusion of adenosine or the 5-HT3 receptor
      selective agonist 2-methyl-5-HT nearly abolished coughing evoked subsequently by
      topical citric acid challenge. Delivering adenosine or 2-methyl-5-HT directly to
      the tracheal mucosa (where few if any nodose C fibers terminate) was without
      effect on citric acid-evoked cough. These actions of pulmonary administration of
      adenosine and 2-methyl-5-HT were accompanied by an increase in respiratory rate,
      but it is unlikely that the change in respiratory pattern caused the decrease in
      coughing, as the rapidly adapting receptor stimulant histamine also produced a
      marked tachypnea but was without effect on cough. In awake guinea pigs, adenosine
      failed to evoke coughing but reduced coughing induced by the nonselective C-fiber
      stimulant capsaicin. We conclude that bronchopulmonary C-fiber subtypes in guinea
      pigs have opposing effects on cough, with airway C fibers arising from the
      jugular ganglia initiating and/or sensitizing the cough reflex and the
      intrapulmonary C fibers arising from the nodose ganglia actively inhibiting cough
      upon activation.

PMID- 29187384
TI  - Role of Depression and Social Isolation at Time of Waitlisting for Survival 8
      Years After Heart Transplantation.
AB  - BACKGROUND: We evaluated depression and social isolation assessed at time of
      waitlisting as predictors of survival in heart transplant (HTx) recipients.
      METHODS AND RESULTS: Between 2005 and 2006, 318 adult HTx candidates were
      enrolled in the Waiting for a New Heart Study, and 164 received transplantation.
      Patients were followed until February 2013. Psychosocial characteristics were
      assessed by questionnaires. Eurotransplant provided medical data at waitlisting,
      transplantation dates, and donor characteristics; hospitals reported medical data
      at HTx and date of death after HTx. During a median follow-up of 70 months (<1-93
      months post-HTx), 56 (38%) of 148 transplanted patients with complete data died.
      Depression scores were unrelated to social isolation, and neither correlated with
      disease severity. Higher depression scores increased the risk of dying (hazard
      ratio=1.07, 95% confidence interval, 1.01, 1.15, P=0.032), which was moderated by
      social isolation scores (significant interaction term; hazard ratio = 0.985, 95%
      confidence interval, 0.973, 0.998; P=0.022). These findings were maintained in
      multivariate models controlling for covariates (P values 0.020-0.039). Actuarial
      1-year/5-year survival was best for patients with low depression who were not
      socially isolated at waitlisting (86% after 1 year, 79% after 5 years). Survival
      of those who were either depressed, or socially isolated or both, was lower,
      especially 5 years posttransplant (56%, 60%, and 62%, respectively). CONCLUSIONS:
      Low depression in conjunction with social integration at time of waitlisting is
      related to enhanced chances for survival after HTx. Both factors should be
      considered for inclusion in standardized assessments and interventions for HTx
      candidates.

PMID- 29187385
TI  - National Trends in Admission and In-Hospital Mortality of Patients With Heart
      Failure in the United States (2001-2014).
AB  - BACKGROUND: To investigate heart failure (HF) hospitalization trends in the
      United States and change in trends after publication of management guidelines.
      METHODS AND RESULTS: Using data from the National Inpatient Sample and the US
      Census Bureau, annual national estimates in HF admissions and in-hospital
      mortality were estimated for years 2001 to 2014, during which an estimated 57.4
      million HF-associated admissions occurred. Rates (95% confidence intervals) of
      admissions and in-hospital mortality among primary HF hospitalizations declined
      by an average annual rate of 3% (2.5%-3.5%) and 3.5% (2.9%-4.0%), respectively.
      Compared with 2001 to 2005, the average annual rate of decline in primary HF
      admissions was more in 2006 to 2009 (ie, 3.4% versus 1.1%; P=0.02). In 2010 to
      2014, primary HF admission continued to decline by an average annual rate of 4.3%
      (95% confidence interval, 3.9%-5.1%), but this was not significantly different
      from 2006 to 2009 (P=0.14). In contrast, there was no further decline in in
      hospital mortality trend after the guideline-release years. For hospitalizations
      with HF as the secondary diagnosis, there was an upward trend in admissions in
      2001 to 2005. However, the trend began to decline in 2006 to 2009, with an
      average annual rate of 2.4% (95% confidence interval, 0.8%-4%). Meanwhile, there
      was a consistent decline in in-hospital mortality by an average annual rate of
      3.7% (95% confidence interval, 3.3%-4.2%) during the study period, but the
      decline was more in 2006 to 2009 compared with 2001 to 2005 (ie, 5.4% versus
      3.4%; P<0.001). Beyond 2009, admission and in-hospital mortality rates continued
      to decline, although this was not significantly better than the preceding
      interval. CONCLUSIONS: From 2001 to 2014, HF admission and in-hospital mortality
      rates declined significantly in the United States; the greatest improvements
      coincided with the publication of the 2005 American College of
      Cardiology/American Heart Association HF guidelines.

PMID- 29187386
TI  - High Incidence of Atrial Fibrillation After Embolic Stroke of Undetermined Source
      in Posterior Cerebral Artery Territory.
AB  - BACKGROUND: Subclinical atrial fibrillation is one possible cause of embolic
      stroke of undetermined source (ESUS). It remains to be elucidated if a specific
      infarction site has a predictive value for detecting subclinical atrial
      fibrillation. We aimed to investigate the predictive value of infarction site in
      patients with ESUS for the detection of atrial tachyarrhythmia (AT) using an
      insertable cardiac monitor. METHODS AND RESULTS: Consecutive 146 patients (84
      men; aged 62+/-12 years) underwent insertable cardiac monitor implantation after
      diagnosis of ESUS. The detection of AT >30 seconds was evaluated. The ESUS
      infarction sites were categorized into internal carotid artery and vertebral
      artery (VA) territories, with ophthalmic artery, anterior cerebral artery, and
      middle cerebral artery as internal carotid artery subterritories, and posterior
      cerebral artery and other vertebrobasilar arteries as VA subterritories. During a
      median follow-up of 387 days, AT was detected in 33 patients (23%). Subclinical
      AT detection was significantly more frequent after VA territorial infarction
      opposed to internal carotid artery infarction (20/57 [35%] versus 13/89 [15%];
      P=0.0039). Kaplan-Meier analysis demonstrated a significantly higher AT detection
      rate after VA infarction (log-rank, P=0.0076). Regression analysis revealed that
      VA territorial infarction, and particularly posterior cerebral artery area
      infarction, was an independent predictor of AT detection. CONCLUSIONS: Patients
      with ESUS in the posterior cerebral artery territory had a higher rate of
      subclinical AT detection than those with other infarct localizations. Our data
      suggest that the possible usefulness of ESUS site to identify candidates for
      direct oral anticoagulation should be confirmed in future research.

PMID- 29187387
TI  - Prognostic Value of Serial Galectin-3 Measurements in Patients With Acute Heart
      Failure.
AB  - BACKGROUND: Several clinical studies have evaluated the association between
      galectin-3 levels and outcome in patients with heart failure (HF). However,
      little is known about the predictive value of repeated galectin-3 measurements.
      This study evaluates the prognostic value of repeated time-dependent galectin-3
      measurements in acute HF patients. METHODS AND RESULTS: In the TRIUMPH
      (Translational Initiative on Unique and Novel Strategies for Management of
      Patients with Heart Failure) clinical cohort study, 496 acute HF patients were
      enrolled in 14 hospitals in The Netherlands, between 2009 and 2014. Repeated
      blood samples (7) were drawn during 1-year follow-up. Associations between
      repeated biomarker measurements and the primary end point were assessed using a
      joint model. Median age was 74 years and 37% were women. The primary end point,
      composite of all-cause mortality and HF rehospitalization, was reached in 188
      patients (40%), during a median follow-up of 325 days (interquartile range 85
      401). The median baseline galectin-3 level was 24 ng/mL (interquartile range 18
      34). The mean number of galectin-3 measurements available per patient was 4.3.
      After adjustment for clinical factors and N-terminal pro-brain natriuretic
      peptide, there was a weak association between baseline galectin-3 and risk of the
      primary end point. When repeated measurements were taken into account, the
      adjusted hazard ratio per 1 SD increase of the galectin-3 level (on the log2
      scale) at any time point increased to 1.67 (95% confidence interval, 1.24-2.23,
      P<0.001). After additional adjustment for repeated N-terminal pro-brain
      natriuretic peptide measurements, the association remained statistically
      significant. CONCLUSIONS: Repeated galectin-3 measurements appeared to be a
      strong predictor of outcome in acute HF patients, independent of N-terminal pro
      brain natriuretic peptide. Hence, galectin-3 may be helpful in clinical practice
      for prognostication and treatment monitoring.

PMID- 29187388
TI  - Effects of Dark Chocolate and Almonds on Cardiovascular Risk Factors in
      Overweight and Obese Individuals: A Randomized Controlled-Feeding Trial.
AB  - BACKGROUND: Consumption of almonds or dark chocolate and cocoa has favorable
      effects on markers of coronary heart disease; however, the combined effects have
      not been evaluated in a well-controlled feeding study. The aim of this study was
      to examine the individual and combined effects of consumption of dark chocolate
      and cocoa and almonds on markers of coronary heart disease risk. METHODS AND
      RESULTS: A randomized controlled, 4-period, crossover, feeding trial was
      conducted in overweight and obese individuals aged 30 to 70 years. Forty-eight
      participants were randomized, and 31 participants completed the entire study.
      Each diet period was 4 weeks long, followed by a 2-week compliance break.
      Participants consumed each of 4 isocaloric, weight maintenance diets: (1) no
      treatment foods (average American diet), (2) 42.5 g/d of almonds (almond diet
      [ALD]), (3) 18 g/d of cocoa powder and 43 g/d of dark chocolate (chocolate diet
      [CHOC]), or (4) all 3 foods (CHOC+ALD). Compared with the average American diet,
      total cholesterol, non-high-density lipoprotein cholesterol, and low-density
      lipoprotein cholesterol after the ALD were lower by 4%, 5%, and 7%, respectively
      (P<0.05). The CHOC+ALD decreased apolipoprotein B by 5% compared with the average
      American diet. For low-density lipoprotein subclasses, compared with the average
      American diet, the ALD showed a greater reduction in large buoyant low-density
      lipoprotein particles (-5.7+/-2.3 versus -0.3+/-2.3 mg/dL; P=0.04), whereas the
      CHOC+ALD had a greater decrease in small dense low-density lipoprotein particles
      (-12.0+/-2.8 versus -5.3+/-2.8 mg/dL; P=0.04). There were no significant
      differences between diets for measures of vascular health and oxidative stress.
      CONCLUSIONS: Our results demonstrate that consumption of almonds alone or
      combined with dark chocolate under controlled-feeding conditions improves lipid
      profiles. Incorporating almonds, dark chocolate, and cocoa into a typical
      American diet without exceeding energy needs may reduce the risk of coronary
      heart disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov.
      Unique identifier: NCT01882881.

PMID- 29187389
TI  - Value of Excess Pressure Integral for Predicting 15-Year All-Cause and
      Cardiovascular Mortalities in End-Stage Renal Disease Patients.
AB  - BACKGROUND: The excess pressure integral (XSPI), derived from analysis of the
      arterial pressure curve, may be a significant predictor of cardiovascular events
      in high-risk patients. We comprehensively investigated the prognostic value of
      XSPI for predicting long-term mortality in end-stage renal disease patients
      undergoing regular hemodialysis. METHODS AND RESULTS: A total of 267 uremic
      patients (50.2% female; mean age 54.2+/-14.9 years) receiving regular
      hemodialysis for more than 6 months were enrolled. Cardiovascular parameters were
      obtained by echocardiography and applanation tonometry. Calibrated carotid
      arterial pressure waveforms were analyzed according to the wave-transmission and
      reservoir-wave theories. Multivariable Cox proportional hazard models were
      constructed to account for age, sex, diabetes mellitus, albumin, body mass index,
      and hemodialysis treatment adequacy. Incremental utility of the parameters to
      risk stratification was assessed by net reclassification improvement. During a
      median follow-up of 15.3 years, 124 deaths (46.4%) incurred. Baseline XSPI was
      significantly predictive of all-cause (hazard ratio per 1 SD 1.4, 95% confidence
      interval 1.15-1.70, P=0.0006) and cardiovascular mortalities (1.47, 1.18-1.84,
      P=0.0006) after accounting for the covariates. The addition of XSPI to the base
      prognostic model significantly improved prediction of both all-cause mortality
      (net reclassification improvement=0.1549, P=0.0012) and cardiovascular mortality
      (net reclassification improvement=0.1535, P=0.0033). XSPI was superior to carotid
      pulse wave velocity, forward and backward wave amplitudes, and left ventricular
      ejection fraction in consideration of overall independent and incremental
      prognostics values. CONCLUSIONS: In end-stage renal disease patients undergoing
      regular hemodialysis, XSPI was significantly predictive of long-term mortality
      and demonstrated an incremental value to conventional prognostic factors.

PMID- 29187390
TI  - Phenotyping of Sleep-Disordered Breathing in Patients With Chronic Heart Failure
      With Reduced Ejection Fraction-the SchlaHF Registry.
AB  - BACKGROUND: Different sleep-disordered breathing (SDB) phenotypes, including
      coexisting obstructive and central sleep apnea (OSA-CSA), have not yet been
      characterized in a large sample of patients with heart failure and reduced
      ejection fraction (HFrEF) receiving guideline-based therapies. Therefore, the aim
      of the present study was to determine the proportion of OSA, CSA, and OSA-CSA, as
      well as periodic breathing, in HFrEF patients with SDB. METHODS AND RESULTS: The
      German SchlaHF registry enrolled patients with HFrEF receiving guideline-based
      therapies, who underwent portable SDB monitoring. Polysomnography (n=2365) was
      performed in patients with suspected SDB. Type of SDB (OSA, CSA, or OSA-CSA), the
      occurrence of periodic breathing (proportion of Cheyne-Stokes respiration >=20%),
      and blood gases were determined in 1557 HFrEF patients with confirmed SDB. OSA,
      OSA-CSA, and CSA were found in 29%, 40%, and 31% of patients, respectively; 41%
      showed periodic breathing. Characteristics differed significantly among SDB
      groups and in those with versus without periodic breathing. There was a
      relationship between greater proportions of CSA and the presence of periodic
      breathing. Risk factors for having CSA rather than OSA were male sex, older age,
      presence of atrial fibrillation, lower ejection fraction, and lower awake carbon
      dioxide pressure (pco2). Periodic breathing was more likely in men, patients with
      atrial fibrillation, older patients, and as left ventricular ejection fraction
      and awake pco2 decreased, and less likely as body mass index increased and
      minimum oxygen saturation decreased. CONCLUSIONS: SchlaHF data show that there is
      wide interindividual variability in the SDB phenotype of HFrEF patients,
      suggesting that individualized management is appropriate. CLINICAL TRIAL
      REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier:
      NCT01500759.

PMID- 29187391
TI  - Implicit Gender Bias and the Use of Cardiovascular Tests Among Cardiologists.
AB  - BACKGROUND: Physicians' gender bias may contribute to gender disparities in
      cardiovascular testing. We used the Implicit Association Test to examine the
      association of implicit gender biases with decisions to use cardiovascular tests.
      METHODS AND RESULTS: In 2014, cardiologists completed Implicit Association Tests
      and a clinical vignette with patient gender randomly assigned. The Implicit
      Association Tests measured implicit gender bias for the characteristics of
      strength and risk taking. The vignette represented an intermediate likelihood of
      coronary artery disease regardless of patient gender: chest pain (part 1)
      followed by an abnormal exercise treadmill test (part 2). Cardiologists rated the
      likelihood of coronary artery disease and the usefulness of stress testing and
      angiography for the assigned patient. Of the 503 respondents (9.3% of eligible;
      87% male, median age of 45 years, 58% in private practice), the majority
      associated strength or risk taking implicitly with male more than female
      patients. The estimated likelihood of coronary artery disease for both parts of
      the vignette was similar by patient gender. The utility of secondary stress
      testing after an abnormal exercise treadmill test was rated as "high" more often
      for female than male patients (32.8% versus 24.3%, P=0.04); this difference did
      not vary with implicit bias. Angiography was more consistently rated as having
      "high" utility for male versus female patients (part 1: 19.7% versus 9.8%; part
      2: 73.7% versus 64.3%; P<0.05 for both); this difference was larger for
      cardiologists with higher implicit gender bias on risk taking (P=0.01).
      CONCLUSIONS: Cardiologists have varying degrees of implicit gender bias. This
      bias explained some, but not all, of the gender variability in simulated clinical
      decision-making for suspected coronary artery disease.

PMID- 29187392
TI  - Visit-to-Visit Variability of Fasting Plasma Glucose and the Risk of
      Cardiovascular Disease and All-Cause Mortality in the General Population.
AB  - BACKGROUND: The association of short-term variability of fasting plasma glucose
      (FPG) and mortality has been well investigated. However, the relationships
      between visit-to-visit variability of FPG over longer periods of follow-up and
      cardiovascular disease (CVD) and all-cause mortality are unclear. This study
      aimed to investigate these relationships. METHODS AND RESULTS: The current
      analysis included 53 607 Chinese participants (mean age, 49.10 years) who were
      free of CVD in the Kailuan study. Participants were divided into 4 categories by
      quartiles of visit-to-visit variability of FPG. Visit-to-visit variability of FPG
      was defined as the coefficient of variation of 3 values of FPG that were measured
      from the examination periods of 2006 to 2007, 2008 to 2009, and 2010 to 2011. Cox
      proportional hazards models were used to calculate hazard ratios and 95%
      confidence intervals for CVD and all-cause mortality. After a mean follow-up of
      4.93 years, 4261 individuals developed CVD and 1545 individuals died. The
      incidence of CVD and all-cause mortality was 5.04 and 5.85 per 1000 person-years,
      respectively. After adjusting for mean FPG and other potential confounders,
      individuals in the highest quartile of variability of FPG compared with
      participants in the lowest quartile showed a 26% greater risk of developing CVD
      (hazard ratio, 1.26; 95% confidence interval, 1.08-1.47) and a 46% greater risk
      for all-cause mortality (hazard ratio, 1.46; 95% confidence interval, 1.25-1.70).
      CONCLUSIONS: Independent of mean FPG and other baseline parameters, elevated
      visit-to-visit variability of FPG significantly increases the risk of CVD and all
      cause mortality in the general population. Measuring long-term visit-to-visit
      variability of FPG is helpful for predicting the risk for CVD and all-cause
      mortality.

PMID- 29187393
TI  - Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid
      Carcinoma Treated with Vandetanib.
AB  - Purpose: Vandetanib is well-tolerated in patients with advanced medullary thyroid
      carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not
      been reported previously.Experimental Design: We monitored toxicities and disease
      status in patients taking vandetanib for hereditary, advanced MTC. Tumor samples
      were analyzed for molecular mechanisms of disease progression.Results: Seventeen
      patients [8 male, age 13 (9-17)* years] enrolled; 16 had a RET p.Met918Thr
      germline mutation. The duration of vandetanib therapy was 6.1 (0.1-9.7+)* years
      with treatment ongoing in 9 patients. Best response was partial response in 10,
      stable disease in 6, and progressive disease in one patient. Duration of response
      was 7.4 (0.6-8.7+)* and 4.9 (0.6-7.8+)* years in patients with PR and SD,
      respectively. Six patients died 2.0 (0.4-5.7)* years after progression. Median
      progression-free survival (PFS) was 6.7 years [95% confidence interval (CI): 2.3
      years-undefined] and 5-year overall survival (OS) was 88.2% (95% CI: 60.6%
      96.9%). Of 16 patients with a RET p.Met918Thr mutation, progression-free survival
      was 6.7 years (95% CI: 3.1-undefined) and 5-year overall survival was 93.8% (95%
      CI: 63.2%-99.1%). No patients terminated treatment because of toxicity. DNA
      sequencing of tissue samples (n = 11) identified an increase in copy number
      alterations across the genome as a potential mechanism of drug resistance
      [*median (range)].Conclusions: This study demonstrates that vandetanib is safe
      and results in sustained responses in children and adolescents with hereditary
      MTC. Our preliminary molecular data suggest that an increase in copy number
      abnormalities may be associated with tumor progression in hereditary MTC patients
      treated with vandetanib. Clin Cancer Res; 24(4); 753-65. (c)2017 AACR.

PMID- 29187395
TI  - New Approaches and Therapeutic Options for Mycobacterium tuberculosis in a
      Dormant State.
AB  - We are far away from the days when tuberculosis (TB) accounted for 1 in 4 deaths
      during the 19th century. However, Mycobacterium tuberculosis complex (MTBC)
      strains are still the leading cause of morbidity and mortality by a single
      infectious disease, with 9.6 million cases and 1.5 million deaths reported. One
      third of the world's population is estimated by the WHO to be infected with
      latent TB. During the last decade, several studies have aimed to define the
      characteristics of dormant bacteria in these latent infections. General features
      of the shift to a dormant state encompass several phenotypic changes that reduce
      metabolic activity. This low metabolic state is thought to increase the
      resistance of MTBC strains to host/environmental stresses, including antibiotic
      action. Once the stress ceases (e.g., interruption of treatment), dormant cells
      can reactivate and cause symptomatic disease again. Therefore, a proper
      understanding of dormancy could guide the rational development of new treatment
      regimens that target dormant cells, reducing later relapse. Here, we briefly
      summarize the latest data on the genetics involved in the regulation of dormancy
      and discuss new approaches to TB treatment.

PMID- 29187394
TI  - Carrion's Disease: the Sound of Silence.
AB  - Carrion's disease (CD) is a neglected biphasic vector-borne illness related to
      Bartonella bacilliformis. It is found in the Andean valleys and is transmitted
      mainly by members of the Lutzomyia genus but also by blood transfusions and from
      mother to child. The acute phase, Oroya fever, presents severe anemia and fever.
      The lethality is high in the absence of adequate treatment, despite the organism
      being susceptible to most antibiotics. Partial immunity is developed after
      infection by B. bacilliformis, resulting in high numbers of asymptomatic
      carriers. Following infection there is the chronic phase, Peruvian warts,
      involving abnormal proliferation of the endothelial cells. Despite potentially
      being eradicable, CD has been expanded due to human migration and geographical
      expansion of the vector. Moreover, in vitro studies have demonstrated the risk of
      the development of antimicrobial resistance. These findings, together with the
      description of new Bartonella species producing CD-like infections, the presence
      of undescribed potential vectors in new areas, the lack of adequate diagnostic
      tools and knowledge of the immunology and bacterial pathogenesis of CD, and poor
      international visibility, have led to the risk of increasing the potential
      expansion of resistant strains which will challenge current treatment schemes as
      well as the possible appearance of CD in areas where it is not endemic.

PMID- 29187399
TI  - Disparities in Prostate, Lung, Breast, and Colorectal Cancer Survival and
      Comorbidity Status among Urban American Indians and Alaskan Natives.
AB  - Cancer is the second leading cause of death among American Indians and Alaskan
      Natives (AIAN), although cancer survival information in this population is
      limited, particularly among urban AIAN. In this retrospective cohort study, we
      compared all-cause and prostate, breast, lung, and colorectal cancer-specific
      mortality among AIAN (n = 582) and non-Hispanic white (NHW; n = 82,696) enrollees
      of Kaiser Permanente Northern California (KPNC) diagnosed with primary invasive
      breast, prostate, lung, or colorectal cancer from 1997 to 2015. Tumor registry
      and other electronic health records provided information on sociodemographic,
      comorbidity, tumor, clinical, and treatment characteristics. Cox regression
      models were used to estimate adjusted survival curves and hazard ratios (HR) with
      95% confidence intervals (CI). AIAN had a significantly higher comorbidity burden
      compared with NHW (P < 0.05). When adjusting for patient, disease
      characteristics, and Charlson comorbidity scores, all-cause mortality and cancer
      specific mortality were significantly higher for AIAN than NHW patients with
      breast cancer (HR, 1.47; 95% CI, 1.13-1.92) or with prostate cancer (HR, 1.87;
      95% CI, 1.14-3.06) but not for AIAN patients with lung and colorectal cancer.
      Despite approximately equal access to preventive services and cancer care in this
      setting, we found higher mortality for AIAN than NHW with some cancers, and a
      greater proportion of AIAN cancer patients with multiple comorbid conditions.
      This study provides severely needed information on the cancer experience of the
      71% of AIANs who live in urban areas and access cancer care outside of the Indian
      Health Services, from which the vast majority of AIAN cancer information comes.
      Cancer Res; 77(23); 6770-6. (c)2017 AACR.

PMID- 29187400
TI  - PPARdelta Elicits Ligand-Independent Repression of Trefoil Factor Family to Limit
      Prostate Cancer Growth.
AB  - The nuclear receptor PPAR-beta/delta (PPARD) has essential roles in fatty acid
      catabolism and energy homeostasis as well as cell differentiation, inflammation,
      and metabolism. However, its contributions to tumorigenesis are uncertain and
      have been disputed. Here, we provide evidence of tumor suppressive activity of
      PPARD in prostate cancer through a noncanonical and ligand-independent pathway.
      PPARD was downregulated in prostate cancer specimens. In murine prostate
      epithelium, PPARD gene deletion resulted in increased cellularity. Genetic
      modulation of PPARD in human prostate cancer cell lines validated the tumor
      suppressive activity of this gene in vitro and in vivo Mechanistically, PPARD
      exerted its activity in a DNA binding-dependent and ligand-independent manner. We
      identified a novel set of genes repressed by PPARD that failed to respond to
      ligand-mediated activation. Among these genes, we observed robust regulation of
      the secretory trefoil factor family (TFF) members, including a causal and
      correlative association of TFF1 with prostate cancer biology in vitro and in
      patient specimens. Overall, our results illuminate the oncosuppressive function
      of PPARD and understanding of the pathogenic molecular pathways elicited by this
      nuclear receptor.Significance: These findings challenge the presumption that the
      function of the nuclear receptor PPARbeta/delta in cancer is dictated by ligand
      mediated activation. Cancer Res; 78(2); 399-409. (c)2017 AACR.

PMID- 29187396
TI  - Recombinant Endolysins as Potential Therapeutics against Antibiotic-Resistant
      Staphylococcus aureus: Current Status of Research and Novel Delivery Strategies.
AB  - Staphylococcus aureus is one of the most common pathogens of humans and animals,
      where it frequently colonizes skin and mucosal membranes. It is of major clinical
      importance as a nosocomial pathogen and causative agent of a wide array of
      diseases. Multidrug-resistant strains have become increasingly prevalent and
      represent a leading cause of morbidity and mortality. For this reason, novel
      strategies to combat multidrug-resistant pathogens are urgently needed.
      Bacteriophage-derived enzymes, so-called endolysins, and other peptidoglycan
      hydrolases with the ability to disrupt cell walls represent possible alternatives
      to conventional antibiotics. These lytic enzymes confer a high degree of host
      specificity and could potentially replace or be utilized in combination with
      antibiotics, with the aim to specifically treat infections caused by Gram
      positive drug-resistant bacterial pathogens such as methicillin-resistant S.
      aureus. LysK is one of the best-characterized endolysins with activity against
      multiple staphylococcal species. Various approaches to further enhance the
      antibacterial efficacy and applicability of endolysins have been demonstrated.
      These approaches include the construction of recombinant endolysin derivatives
      and the development of novel delivery strategies for various applications, such
      as the production of endolysins in lactic acid bacteria and their conjugation to
      nanoparticles. These novel strategies are a major focus of this review.

PMID- 29187401
TI  - Delivering Type I Interferon to Dendritic Cells Empowers Tumor Eradication and
      Immune Combination Treatments.
AB  - An ideal generic cancer immunotherapy should mobilize the immune system to
      destroy tumor cells without harming healthy cells and remain active in case of
      recurrence. Furthermore, it should preferably not rely on tumor-specific surface
      markers, as these are only available in a limited set of malignancies. Despite
      approval for treatment of various cancers, clinical application of cytokines is
      still impeded by their multiple toxic side effects. Type I IFN has a long history
      in the treatment of cancer, but its multifaceted activity pattern and complex
      side effects prevent its clinical use. Here we develop AcTakines (Activity-on
      Target cytokines), optimized (mutated) immunocytokines that are up to 1,000-fold
      more potent on target cells, allowing specific signaling in selected cell types
      only. Type I IFN-derived AcTaferon (AFN)-targeting Clec9A+ dendritic cells (DC)
      displayed strong antitumor activity in murine melanoma, breast carcinoma, and
      lymphoma models and against human lymphoma in humanized mice without any
      detectable toxic side effects. Combined with immune checkpoint blockade,
      chemotherapy, or low-dose TNF, complete tumor regression and long-lasting tumor
      immunity were observed, still without adverse effects. Our findings indicate that
      DC-targeted AFNs provide a novel class of highly efficient, safe, and broad
      spectrum off-the-shelf cancer immunotherapeutics with no need for a tumor
      marker.Significance: Targeted type I interferon elicits powerful antitumor
      efficacy, similar to wild-type IFN, but without any toxic side effects. Cancer
      Res; 78(2); 463-74. (c)2017 AACR.

PMID- 29187397
TI  - The Spirochete Brachyspira pilosicoli, Enteric Pathogen of Animals and Humans.
AB  - Brachyspira pilosicoli is a slow-growing anaerobic spirochete that colonizes the
      large intestine. Colonization occurs commonly in pigs and adult chickens, causing
      colitis/typhlitis, diarrhea, poor growth rates, and reduced production.
      Colonization of humans also is common in some populations (individuals living in
      village and peri-urban settings in developing countries, recent immigrants from
      developing countries, homosexual males, and HIV-positive patients), but the
      spirochete rarely is investigated as a potential human enteric pathogen. In part
      this is due to its slow growth and specialized growth requirements, meaning that
      it is not detectable in human fecal samples using routine diagnostic methods.
      Nevertheless, it has been identified histologically attached to the colon and
      rectum in patients with conditions such as chronic diarrhea, rectal bleeding,
      and/or nonspecific abdominal discomfort, and one survey of Australian Aboriginal
      children showed that colonization was significantly associated with failure to
      thrive. B. pilosicoli has been detected in the bloodstream of elderly patients or
      individuals with chronic conditions such as alcoholism and malignancies. This
      review describes the spirochete and associated diseases. It aims to encourage
      clinicians and clinical microbiologists to consider B. pilosicoli in their
      differential diagnoses and to develop and use appropriate diagnostic protocols to
      identify the spirochete in clinical specimens.

PMID- 29187402
TI  - The E3 Ligase RING1 Targets p53 for Degradation and Promotes Cancer Cell
      Proliferation and Survival.
AB  - As a component of the transcriptional repression complex 1 (PRC1), the ring
      finger protein RING1 participates in the epigenetic regulation in cancer.
      However, the contributions of RING1 to cancer etiology or development are
      unknown. In this study, we report that RING1 is a critical negative regulator of
      p53 homeostasis in human hepatocellular and colorectal carcinomas. RING1 acts as
      an E3 ubiquitin (Ub) ligase to directly interact with and ubiquitinate p53,
      resulting in its proteasome-dependent degradation. The RING domain of RING1 was
      required for its E3 Ub ligase activity. RING1 depletion inhibited the
      proliferation and survival of the p53 wild-type cancer cells by inducing cell
      cycle arrest, apoptosis, and senescence, with only modest effects on p53
      deficient cells. Its growth inhibitory effect was partially rescued by p53
      silencing, suggesting an important role for the RING1-p53 complex in human
      cancer. In clinical specimens of hepatocellular carcinoma, RING1 upregulation was
      evident in association with poor clinical outcomes. Collectively, our results
      elucidate a novel PRC1-independent function of RING1 and provide a mechanistic
      rationale for its candidacy as a new prognostic marker and/or therapeutic target
      in human cancer.Significance: These results elucidate a novel PRC1-independent
      function of RING1 and provide a mechanistic rationale for its candidacy as a new
      prognostic marker and/or therapeutic target in human cancer. Cancer Res; 78(2);
      359-71. (c)2017 AACR.

PMID- 29187403
TI  - Photodynamic Priming Mitigates Chemotherapeutic Selection Pressures and Improves
      Drug Delivery.
AB  - Physiologic barriers to drug delivery and selection for drug resistance limit
      survival outcomes in cancer patients. In this study, we present preclinical
      evidence that a subtumoricidal photodynamic priming (PDP) strategy can relieve
      drug delivery barriers in the tumor microenvironment to safely widen the
      therapeutic window of a nanoformulated cytotoxic drug. In orthotopic xenograft
      models of pancreatic cancer, combining PDP with nanoliposomal irinotecan (nal
      IRI) prevented tumor relapse, reduced metastasis, and increased both progression
      free survival and 1-year disease-free survival. PDP enabled these durable
      improvements by targeting multiple tumor compartments to (i) increase
      intratumoral drug accumulation by >10-fold, (ii) increase the duration of drug
      exposure above a critical therapeutic threshold, and (iii) attenuate surges in
      CD44 and CXCR4 expression, which mediate chemoresistance often observed after
      multicycle chemotherapy. Overall, our results offer preclinical proof of concept
      for the effectiveness of PDP to minimize risks of tumor relapse, progression, and
      drug resistance and to extend patient survival.Significance: A biophysical
      priming approach overcomes key treatment barriers, significantly reduces
      metastases, and prolongs survival in orthotopic models of human pancreatic
      cancer. Cancer Res; 78(2); 558-71. (c)2017 AACR.

PMID- 29187404
TI  - LSR Antibody Therapy Inhibits Ovarian Epithelial Tumor Growth by Inhibiting Lipid
      Uptake.
AB  - Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, but it
      still lacks effective treatment options. In this study, we utilized proteomic
      technology to identify lipolysis-stimulated lipoprotein receptor (LSR) as a new
      tumor antigen of EOC. Immunohistochemical analysis of EOC tissues in conjunction
      with survival analysis of EOC patients showed that high expression of LSR is
      associated with poor prognosis. High LSR expression also occurred in tumor
      metastases including to the lymph node and omentum. To evaluate the possible
      benefits of blocking this antigen in EOC, we raised a new monoclonal antibody
      (mAb) to human LSR (hLSR). In mouse xenograft models of hLSR+ EOC (cell lines or
      patient-derived tumors), we found that administration of anti-hLSR mAb inhibited
      tumor growth in a manner independent of both antibody-dependent cellular
      cytotoxicity and complement-dependent cytotoxicity. Mechanistic investigations
      showed that hLSR expression increased incorporation of very-low-density
      lipoprotein (VLDL) into EOC cells and that anti-hLSR mAb inhibited lipid uptake
      in vitro and in vivo Moreover, VLDL promoted cell proliferation in hLSR-positive
      EOC cells in vitro, and this effect was inhibited by anti-hLSR mAb. While the
      anti-hLSR mAb studied cross reacted with the mouse antigen, we observed no
      adverse effects on normal organs and lipid metabolism in murine hosts. Our
      findings suggest that hLSR plays a key functional role in EOC development and
      that this antigen can be therapeutically targeted by specific mAb to improve EOC
      treatment.Significance: These findings offer preclinical evidence of the
      therapeutic efficacy of a novel targeted antibody therapy against deadly
      epithelial ovarian cancers. Cancer Res; 78(2); 516-27. (c)2017 AACR.

PMID- 29187405
TI  - HER2-Driven Breast Tumorigenesis Relies upon Interactions of the Estrogen
      Receptor with Coactivator MED1.
AB  - Studies of the estrogen receptor (ER) coactivator protein Mediator subunit 1
      (MED1) have revealed its specific roles in pubertal mammary gland development and
      potential contributions to breast tumorigenesis, based on coamplification of MED1
      and HER2 in certain breast cancers. In this study, we generated a mouse model of
      mammary tumorigenesis harboring the MMTV-HER2 oncogene and mutation of MED1 to
      evaluate its role in HER2-driven tumorigenesis. MED1 mutation in its ER
      interacting LxxLL motifs was sufficient to delay tumor onset and to impair tumor
      growth, metastasis, and cancer stem-like cell formation in this model.
      Mechanistic investigations revealed that MED1 acted directly to regulate ER
      signaling through the downstream IGF1 pathway but not the AREG pathway. Our
      findings show that MED1 is critical for HER2-driven breast tumorigenesis,
      suggesting its candidacy as a disease-selective therapeutic target.Significance:
      These findings identify an estrogen receptor-binding protein as a critical
      mediator of HER2-driven breast tumorigenesis, suggesting its candidacy as a
      disease-selective therapeutic target. Cancer Res; 78(2); 422-35. (c)2017 AACR.

PMID- 29187406
TI  - PTBP3-Mediated Regulation of ZEB1 mRNA Stability Promotes Epithelial-Mesenchymal
      Transition in Breast Cancer.
AB  - The RNA polypyrimidine tract-binding protein PTBP3 is a little studied paralog of
      PTBP1, which has oncogenic properties. In this study, we demonstrate that PTBP3
      induces epithelial-mesenchymal transition (EMT) in breast tumor cells and
      promotes their invasive growth and metastasis. Elevated expression of PTBP3
      associated significantly with lymph node metastasis, advanced histology grade,
      TNM stage, and poor 5-year overall survival of patients. In human mammary
      epithelial cells, PTBP3 overexpression was sufficient to induce EMT and to
      enhance cell migration, invasion, and cancer stem-like cell properties. PTBP3
      regulated expression of the EMT regulatory transcription factor ZEB1 by binding
      the 3'UTR of its mRNA, thereby preventing its degradation. Conversely, ZEB1
      ablation blocked the ability of PTBP3 to induce EMT. Overall, our findings define
      PTBP3 as a regulator of EMT that acts by governing expression of ZEB1, and they
      establish an oncogenic function of PTBP3, suggesting its candidacy as a
      theranostic target.Significance: These findings define PTBP3 as a regulator of
      EMT that acts by governing expression of ZEB1, and they establish an oncogenic
      function of PTBP3, suggesting its candidacy as a theranostic target. Cancer Res;
      78(2); 387-98. (c)2017 AACR.

PMID- 29187407
TI  - Modeling the Subclonal Evolution of Cancer Cell Populations.
AB  - Increasing evidence shows that tumor clonal architectures are often the
      consequence of a complex branching process, yet little is known about the
      expected dynamics and extent to which these divergent subclonal expansions occur.
      Here, we develop and implement more than 88,000 instances of a stochastic
      evolutionary model simulating genetic drift and neoplastic progression. Under
      different combinations of population genetic parameter values, including those
      estimated for colorectal cancer and glioblastoma multiforme, the distribution of
      sizes of subclones carrying driver mutations had a heavy right tail at the time
      of tumor detection, with only 1 to 4 dominant clones present at >=10% frequency.
      In contrast, the vast majority of subclones were present at <10% frequency, many
      of which had higher fitness than currently dominant clones. The number of
      dominant clones (>=10% frequency) in a tumor correlated strongly with the number
      of subclones (<10% of the tumor). Overall, these subclones were frequently below
      current standard detection thresholds, frequently harbored treatment-resistant
      mutations, and were more common in slow-growing tumors.Significance: The model
      presented in this paper addresses tumor heterogeneity by framing expectations for
      the number of resistant subclones in a tumor, with implications for future
      studies of the evolution of therapeutic resistance. Cancer Res; 78(3); 830-9.
      (c)2017 AACR.

PMID- 29187408
TI  - Review of systematic reviews of non-pharmacological interventions to improve
      quality of life in cancer survivors.
AB  - OBJECTIVES: Over two million people in the UK are living with and beyond cancer.
      A third report diminished quality of life. DESIGN: A review of published
      systematic reviews to identify effective non-pharmacological interventions to
      improve the quality of life of cancer survivors. DATA SOURCES: Databases searched
      until May 2017 included PubMed, Cochrane Central, EMBASE, MEDLINE, Web of
      Science, the Cumulative Index to Nursing and Allied Health Literature, and
      PsycINFO. STUDY SELECTION: Published systematic reviews of randomised trials of
      non-pharmacological interventions for people living with and beyond cancer were
      included; included reviews targeted patients aged over 18. All participants had
      already received a cancer diagnosis. Interventions located in any healthcare
      setting, home or online were included. Reviews of alternative therapies or those
      non-English reports were excluded. Two researchers independently assessed titles,
      abstracts and the full text of papers, and independently extracted the data.
      OUTCOMES: The primary outcome of interest was any measure of global (overall)
      quality of life. ANALYTICAL METHODS: Quality assessment assessing methdological
      quality of systematic reviews (AMSTAR) and narrative synthesis, evaluating
      effectiveness of non-pharmacological interventions and their components. RESULTS:
      Of 14 430 unique titles, 21 were included in the review of reviews. There was
      little overlap in the primary papers across these reviews. Thirteen reviews
      covered mixed tumour groups, seven focused on breast cancer and one focused on
      prostate cancer. Face-to-face interventions were often combined with online,
      telephone and paper-based reading materials. Interventions included physical,
      psychological or behavioural, multidimensional rehabilitation and online
      approaches. Yoga specifically, physical exercise more generally, cognitive
      behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR)
      programmes showed benefit in terms of quality of life. CONCLUSIONS: Exercise
      based interventions were effective in the short (less than 3-8 months) and long
      term. CBT and MBSR also showed benefits, especially in the short term. The
      evidence for multidisciplinary, online and educational interventions was
      equivocal.

PMID- 29187409
TI  - Study of depression influencing factors with zero-inflated regression models in a
      large-scale population survey.
AB  - OBJECTIVES: The number of depression symptoms can be considered as count data in
      order to get complete and accurate analyses findings in studies of depression.
      This study aims to compare the goodness of fit of four count outcomes models by a
      large survey sample to identify the optimum model for a risk factor study of the
      number of depression symptoms. METHODS: 15 820 subjects, aged 10 to 80 years old,
      who were not suffering from serious chronic diseases and had not run a high fever
      in the past 15 days, agreed to take part in this survey; 15 462 subjects
      completed all the survey scales. The number of depression symptoms was the sum of
      the 'positive' responses of seven depression questions. Four count outcomes
      models and a logistic model were constructed to identify the optimum model of the
      number of depression symptoms. RESULTS: The mean number of depression symptoms
      was 1.37+/-1.55. The over-dispersion test statistic O was 308.011. The alpha
      dispersion parameter was 0.475 (95% CI 0.443 to 0.508), which was significantly
      larger than 0. The Vuong test statistic Z was 6.782 and the P value was <0.001,
      which showed that there were too many zero counts to be accounted for with
      traditional negative binomial distribution. The zero-inflated negative binomial
      (ZINB) model had the largest log likelihood and smallest AIC and BIC, suggesting
      best goodness of fit. In addition, predictive probabilities for many counts in
      the ZINB model fitted the observed counts best. CONCLUSIONS: All fitting test
      statistics and the predictive probability curve produced the same findings that
      the ZINB model was the best model for fitting the number of depression symptoms,
      assessing both the presence or absence of depression and its severity.

PMID- 29187410
TI  - Protective effect of smoking against pterygium development in men: a nationwide
      longitudinal cohort study in South Korea.
AB  - OBJECTIVE: The present study aimed to evaluate the association between smoking
      and incident pterygium in adult Korean men. DESIGN: A retrospective nationwide
      longitudinal cohort. SETTING: National Health Insurance database of South Korea.
      PARTICIPANTS: This study included Korean men (age range: 40-79 years) registered
      in the Korea National Health Insurance Service database from 2002 through 2013.
      We compared HRs for pterygium between 90 547 current/past and 90 547 never
      smokers via 1:1 propensity-matched analysis. PRIMARY OUTCOME MEASURE: Incident
      cases of pterygium were identified from the database. RESULTS: Pterygium
      developed in 5389 (6.0%) never-smokers and 3898 (4.3%) past/current smokers
      (P<0.001). The incidence of pterygium per 1000 person-years in never-smokers and
      in past/current smokers was 6.5 and 4.7, respectively (age-adjusted HR, 0.73; 95%
      CI, 0.70 to 0.76). This protective effect was more pronounced among current
      smokers than among past smokers (for current smokers: HR, 0.68; 95% CI, 0.65 to
      0.71 and for past smokers: HR, 0.85; 95% CI, 0.80 to 0.90). A longer duration of
      smoking and higher amounts of cigarette consumption were associated with a lower
      incidence of pterygium. CONCLUSIONS: Longitudinally, cigarette smoking was
      associated with a reduced risk of pterygium, and this protective effect was more
      pronounced among current smokers than among past smokers.

PMID- 29187411
TI  - Lived experience of women with gestational diabetes mellitus living in China: a
      qualitative interview study.
AB  - OBJECTIVE: To explore the lived experience of women with gestational diabetes
      mellitus (GDM) living in China in order to add knowledge about how the Chinese
      women suffer from GDM. DESIGN: A qualitative interpretive interview study. Data
      were collected with a snowball sampling technique. Phenomenological hermeneutics
      was used as the analysis method based on Ricoeur's phenomenological hermeneutical
      interpretation theory. SETTING: The study was performed at the participants' work
      places, or at the obstetric clinics or wards at two provincial hospitals and one
      municipal hospital in the southeast of China. PARTICIPANTS: Inclusion criteria
      were age >=18 years, diagnosis of GDM without other pregnancy complications, in
      34th gestational weeks-postpartum 4th weeks and speaking Mandarin Chinese without
      speech impediment. 62 women, who met the inclusion criteria, took part in the
      study. RESULTS: The lived experience of the women with GDM living in China was
      formulated into a main theme: 'longing for caring care'. The main theme was
      derived from four themes: being stricken by GDM, wishing to receive caring GDM
      care, being left alone to struggle with GDM and trying to adjust and adapt to
      life with GDM. CONCLUSION: The eagerness for caring care in China was
      highlighted. The lack of caring care could be one of the possible reasons why the
      professional-patient relations were deteriorating in China. It could be useful
      for health providers and health policymakers to receive education and training
      about caring care. Using the health metaphor of balance and 'patient
      participation' and 'patient-centred' approaches may benefit women with GDM and
      thus improve the quality of care in China.

PMID- 29187412
TI  - Protocol for the melatools skin self-monitoring trial: a phase II randomised
      controlled trial of an intervention for primary care patients at higher risk of
      melanoma.
AB  - INTRODUCTION: Melanoma is the fifth most common cancer in the UK. Incidence rates
      have quadrupled over the last 30 years and continue to rise, especially among
      younger people. As routine screening of the general population is not currently
      recommended in the UK, a focus on secondary prevention through early detection
      and prompt treatment in individuals at increased risk of melanoma could make an
      important contribution to improve melanoma outcomes. This paper describes the
      protocol for a phase II, multisite, randomised controlled trial, in the primary
      care setting, for patients at increased risk of melanoma. A skin self-monitoring
      (SSM) smartphone 'App' was used to improve symptom appraisal and encourage help
      seeking in primary care, thereby promoting early presentation with skin changes
      suspicious of melanoma. METHODS AND ANALYSIS: We aim to recruit 200 participants
      from general practice waiting rooms in the East of England. Eligible patients are
      those identified at higher melanoma risk (using a real-time risk assessment
      tool), without a personal history of melanoma, aged 18 to 75 years. Participants
      will be invited to a primary care nurse consultation, and randomised to the
      intervention group (standard written advice on skin cancer detection and sun
      protection, loading of an SSM 'App' onto the participant's smartphone and
      instructions on use including self-monitoring reminders) or control group
      (standard written advice alone). The primary outcomes are consultation rates for
      changes to a pigmented skin lesion, and the patient interval (time from first
      noticing a skin change to consultation). Secondary outcomes include patient sun
      protection behaviours, psychosocial outcomes, and measures of trial feasibility
      and acceptability. ETHICS AND DISSEMINATION: NHS ethical approval has been
      obtained from Cambridgeshire and Hertfordshire research ethics committee (REC
      reference 16/EE/0248). The findings from the MelaTools SSM Trial will be
      disseminated widely through peer-reviewed publications and scientific
      conferences. TRIAL REGISTRATION NUMBER: ISCTRN16061621.

PMID- 29187413
TI  - Impact of inhalational versus intravenous anaesthesia on early delirium and long
      term survival in elderly patients after cancer surgery: study protocol of a
      multicentre, open-label, and randomised controlled trial.
AB  - INTRODUCTION: Elderly patients who have solid organ cancer often receive surgery.
      Some of them may develop delirium after surgery and delirium development is
      associated with worse outcomes. Furthermore, despite all of the advances in
      medical care, the long-term survival in cancer patients is far from optimal.
      Evidences suggest that choice of anaesthetics during surgery, that is, either
      inhalational or intravenous anaesthetics, may influence outcomes. However, the
      impact of general anaesthesia type on the occurrence of postoperative delirium is
      inconclusive. Although retrospective studies suggest that propofol-based
      intravenous anaesthesia was associated with longer survival after cancer surgery
      when compared with inhalational anaesthesia, prospective studies as such are
      still lacking. The purposes of this randomised controlled trial are to test the
      hypotheses that when compared with sevoflurane-based inhalational anaesthesia,
      propofol-based intravenous anaesthesia may reduce the incidence of early delirium
      and prolong long-term survival in elderly patients after major cancer surgery.
      METHODS AND ANALYSIS: This is a multicentre, open-label, randomised controlled
      trial with two parallel arms. 1200 elderly patients (>=65 years but <90 years)
      who are scheduled to undergo major cancer surgery (with predicted duration >=2
      hours) are randomised to receive either sevoflurane-based inhalational
      anaesthesia or propofol-based intravenous anaesthesia. Other anaesthetics and
      supplemental drugs including sedatives, opioids and muscle relaxants are
      administered in both arms according to routine practice. The primary early
      outcome is the incidence of 7-day delirium after surgery and the primary long
      term outcome is the duration of 3-year survival after surgery. ETHICS AND
      DISSEMINATION: The study protocol has been approved by the Clinical Research
      Ethics Committees of Peking University First Hospital (2015[869]) and all
      participating centres. The results of early and long-term outcomes will be
      analysed and reported separately. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-15006209;
      NCT02662257; NCT02660411.

PMID- 29187414
TI  - Postpartum management of hypertensive disorders of pregnancy: a systematic
      review.
AB  - OBJECTIVES: Hypertensive disorders of pregnancy (HDP) affect one in ten
      pregnancies and often persist postpartum when complications can occur. We aimed
      to determine the effectiveness and safety of pharmacological interventions, other
      interventions and different care models for postpartum hypertension management.
      DESIGN: A systematic review was undertaken. Nine electronic databases, including
      Medline, were searched from inception to 16 March 2017. After duplicate removal,
      4561 records were screened. Two authors independently selected studies, extracted
      study characteristics and data, and assessed methodological quality. SETTING:
      Randomised controlled trials, case-control studies and cohort studies from any
      country and healthcare setting. PARTICIPANTS: Postnatal women with HDP.
      INTERVENTIONS: Therapeutic intervention for management of hypertension, compared
      with another intervention, placebo or no intervention. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Outcome data were collected for maternal mortality and severe
      morbidity; systolic, diastolic and mean arterial blood pressure (BP) control; and
      safety data. Secondary outcome data collected included the length of postnatal
      hospital stay and laboratory values. RESULTS: 39 studies were included (n=2901).
      Results were heterogeneous in terms of intervention, comparison and outcome
      requiring a narrative approach. There were insufficient data to recommend any
      single pharmacological intervention. 18 studies reported calcium-channel
      blockers, vasodilators and beta-blockers lowered BP postpartum. 12 of these
      reported safety data. Limited data existed regarding management in the weeks
      following hospital discharge. Neither loop diuretics (three studies) nor
      corticosteroids (one study) produced clinical benefit. Uterine curettage
      significantly reduced BP over the first 48 hours postpartum (range 6-13 mm Hg)
      compared with standard care (eight studies), with safety data only reported by
      four of eight studies. CONCLUSION: There was insufficient evidence to recommend a
      particular BP threshold, agent or model of care, but three classes of
      antihypertensive appeared variably effective. Further comparative research,
      including robust safety data, is required. Curettage reduced BP, but without
      adequate reporting of harms, so it cannot currently be recommended.

PMID- 29187415
TI  - Is insomnia a risk factor for new-onset asthma? A population-based study in
      Taiwan.
AB  - OBJECTIVES: To determine whether insomnia at baseline is a risk factor for new
      onset asthma. METHODS: We recruited 48 871 patients with insomnia (insomnia
      group) newly diagnosed between 2002 and 2007, and 97 742 matched controls without
      insomnia (control group) from Taiwan's Longitudinal Health Insurance Database
      2000. All of the patients were followed up for 4 years to see whether new-onset
      asthma developed. Patients with previous asthma or insomnia were excluded. The
      Poisson regression was used to estimate the incidence rate ratios (IRRs) and 95%
      CIs of asthma. Cox proportional hazard regression was used to calculate the risk
      of asthma between the two groups. RESULTS: After a 4-year follow-up, 424 patients
      in the insomnia group and 409 in the control group developed asthma. The
      incidence rate of asthma was significantly higher in the insomnia group
      (22.01vs10.57 per 10 000 person-years). Patients with insomnia have a higher risk
      of developing new-onset asthma during the 4-year follow-up (HR: 2.08, 95% CI 1.82
      to 2.39). The difference remained significant after adjustment (adjusted HR:
      1.89, 95% CI 1.64 to 2.17). CONCLUSIONS: This large population-based study
      suggests that insomnia at baseline is a risk factor for developing asthma.

PMID- 29187416
TI  - Improving hearing and vision in dementia: protocol for a field trial of a new
      intervention.
AB  - INTRODUCTION: Quality of life and other key outcomes may be improved by
      optimising hearing and vision function in people living with dementia. To date,
      there is limited research assessing the efficacy of interventions aimed at
      improving hearing and vision in people with dementia. Here, we outline a protocol
      to field test a newly developed home-based intervention, designed to optimise
      sensory functioning in people with dementia in three European sites. The results
      of this study will inform the design and conduct of a full-scale randomised
      controlled trial (RCT) in five European sites. METHODS AND ANALYSIS: In this
      multisite, single arm, open label, feasibility study, participants with dementia
      (n=24) will be assessed for hearing and vision impairments and be prescribed a
      hearing aid and/or glasses. Each participant will have a study partner ('dyads').
      A subset of dyads will receive 'sensory support' from a 'sensory support
      therapist', comprising home visits over 12 weeks. The therapist will offer the
      following intervention: adherence support for corrective devices; adaptations to
      the home environment to facilitate sensory function; communication training; and
      referral to community-based support services. The primary outcomes will be
      process measures assessing the feasibility, tolerability and acceptability of:
      (1) the intervention components; (2) the method of implementation of the
      intervention and (3) the study procedures, including outcome assessment measures.
      Quantitative data will be collected at baseline and follow-up. Qualitative data
      using semistructured interviews will be collected postintervention and weekly,
      using participant diaries. Finally, we will explore a model of cost-effectiveness
      to apply in the subsequent full-scale trial. This feasibility study is a
      necessary step in the development of a complex, individualised, psychosocial
      intervention. The data gathered will allow logistical and theoretical processes
      to be refined in preparation for a full-scale RCT. ETHICS AND DISSEMINATION:
      Ethical approval was obtained in all three participating countries. Results of
      the field trial will be submitted for publication in a peer-reviewed journal.

PMID- 29187417
TI  - Use of humour in medical education: a survey of students and teachers at a
      medical school in China.
AB  - OBJECTIVE: Humour is a powerful resource in medical education. The purpose of
      this study is to investigate what students and teachers think about the use of
      humour. What challenges do teachers face in using humour and how they address
      them are also the subject of the present study. DESIGN: Separate cross-sectional
      questionnaire surveys. SETTING: Tongji Medical College and Tongji Hospital in
      China. PARTICIPANTS: 327 students at Tongji Medical College and 165 physician
      teachers at Tongji Hospital in China. MAIN OUTCOME MEASURES: The primary study
      outcome was assessed by proportion. RESULTS: 87% of student and teacher
      respondents agreed with using humour in the didactic setting. They felt humour
      fostered a positive didactic atmosphere. Interesting clinical case was the most
      frequently used humour type by teachers and considered the most effective by
      students. Lack of humorous materials related to the lecture subject was the main
      challenge to humour use cited by teachers. Collecting humorous materials in
      teacher's daily work and life, observing teachers with a reputation for
      successfully using humour, and efficiently using the internet-enhanced humour use
      ability. CONCLUSION: The present study confirms that most medical students and
      physician teachers support the use of humour in medical didactics, with
      particular strategies aiding its use and positive impact.

PMID- 29187418
TI  - A rapid review to identify physical activity accrued while playing golf.
AB  - OBJECTIVE: To identify physical activity (PA) accrued while playing golf and
      modifiers of PA accrued. DESIGN: A rapid review of primary research studies.
      Quality was assessed using the National Heart, Lung, and Blood Institute quality
      assessment tool for cohort and cross-sectional studies. METHODS AND OUTCOMES: The
      following databases were searched from 1900 to March 2017: SPORTDiscus, Web of
      Science, PsycINFO, MEDLINE, Google Scholar, Google Advanced Search, ProQuest, WHO
      International Clinical Trials Registry Platform. All primary research
      investigating golf or golfers with any of the following outcomes was included:
      metabolic equivalent of task, oxygen uptake, energy expenditure, heart rate, step
      count, distance covered, strength, flexibility, balance, sedentary behaviour.
      RESULTS: Phase one searching identified 4944 citations and phase two searching
      identified 170 citations. In total, 19 articles met inclusion criteria. Golf is
      primarily a moderate intensity PA, but may be low intensity depending on the
      playing population and various modifiers. Less PA is accrued by those who ride a
      golf cart compared with those walking the course. CONCLUSIONS: Golf can be
      encouraged in order to attain PA recommendations. Further research is required
      into the relationship between golf and strength and flexibility PA
      recommendations and how modifiers affect PA accrued. PROSPERO REGISTRATION
      NUMBER: CRD42017058237.

PMID- 29187419
TI  - Dissecting the Genetic Architecture of Shoot Growth in Carrot (Daucus carota L.)
      Using a Diallel Mating Design.
AB  - Crop establishment in carrot (Daucus carota L.) is limited by slow seedling
      growth and delayed canopy closure, resulting in high management costs for weed
      control. Varieties with improved growth habit (i.e., larger canopy and increased
      shoot biomass) may help mitigate weed control, but the underlying genetics of
      these traits in carrot is unknown. This project used a diallel mating design
      coupled with recent Bayesian analytical methods to determine the genetic basis of
      carrot shoot growth. Six diverse carrot inbred lines with variable shoot size
      were crossed in WI in 2014. F1 hybrids, reciprocal crosses, and parental selfs
      were grown in a randomized complete block design with two blocks in WI (2015) and
      CA (2015, 2016). Measurements included canopy height, canopy width, shoot
      biomass, and root biomass. General and specific combining abilities were
      estimated using Griffing's Model I, which is a common analysis for plant breeding
      experiments. In parallel, additive, inbred, cross-specific, and maternal effects
      were estimated from a Bayesian mixed model, which is robust to dealing with data
      imbalance and outliers. Both additive and nonadditive effects significantly
      influenced shoot traits, with nonadditive effects playing a larger role early in
      the growing season, when weed control is most critical. Results suggest the
      presence of heritable variation and thus potential for improvement of these
      phenotypes in carrot. In addition, results present evidence of heterosis for root
      biomass, which is a major component of carrot yield.

PMID- 29187420
TI  - Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on
      Response to Influenza A Virus in Mice.
AB  - Influenza A virus (IAV) is a respiratory pathogen that causes substantial
      morbidity and mortality during both seasonal and pandemic outbreaks. Infection
      outcomes in unexposed populations are affected by host genetics, but the host
      genetic architecture is not well understood. Here, we obtain a broad view of how
      heritable factors affect a mouse model of response to IAV infection using an 8 *
      8 diallel of the eight inbred founder strains of the Collaborative Cross (CC).
      Expanding on a prior statistical framework for modeling treatment response in
      diallels, we explore how a range of heritable effects modify acute host response
      to IAV through 4 d postinfection. Heritable effects in aggregate explained ~57%
      of the variance in IAV-induced weight loss. Much of this was attributable to a
      pattern of additive effects that became more prominent through day 4
      postinfection and was consistent with previous reports of antiinfluenza myxovirus
      resistance 1 (Mx1) polymorphisms segregating between these strains; these
      additive effects largely recapitulated haplotype effects observed at the Mx1
      locus in a previous study of the incipient CC, and are also replicated here in a
      CC recombinant intercross population. Genetic dominance of protective Mx1
      haplotypes was observed to differ by subspecies of origin: relative to the
      domesticus null Mx1 allele, musculus acts dominantly whereas castaneus acts
      additively. After controlling for Mx1, heritable effects, though less distinct,
      accounted for ~34% of the phenotypic variance. Implications for future mapping
      studies are discussed.

PMID- 29187421
TI  - Identifying Genetic Differences Between Dongxiang Blue-Shelled and White Leghorn
      Chickens Using Sequencing Data.
AB  - The Dongxiang Blue-shelled chicken is one of the most valuable Chinese indigenous
      poultry breeds. However, compared to the Italian native White Leghorn, although
      this Chinese breed possesses numerous favorable characteristics, it also exhibits
      lower growth performance and fertility. Here, we utilized genotyping sequencing
      data obtained via genome reduction on a sequencing platform to detect 100,114
      single nucleotide polymorphisms and perform further biological analysis and
      functional annotation. We employed cross-population extended haplotype
      homozygosity, eigenvector decomposition combined with genome-wide association
      studies (EigenGWAS), and efficient mixed-model association expedited methods to
      detect areas of the genome that are potential selected regions (PSR) in both
      chicken breeds, and performed gene ontology (GO) enrichment and quantitative
      trait loci (QTL) analyses annotating using the Kyoto Encyclopedia of Genes and
      Genomes. The results of this study revealed a total of 2424 outlier loci (p-value
      <0.01), of which 2144 occur in the White Leghorn breed and 280 occur in the
      Dongxiang Blue-shelled chicken. These correspond to 327 and 94 PSRs containing
      297 and 54 genes, respectively. The most significantly selected genes in Blue
      shelled chicken are TMEM141 and CLIC3, while the SLCO1B3 gene, related to
      eggshell color, was identified via EigenGWAS. We show that the White Leghorn
      genes JARID2, RBMS3, GPC3, TRIB2, ROBO1, SAMSN1, OSBP2, and IGFALS are involved
      in immunity, reproduction, and growth, and thus might represent footprints of the
      selection process. In contrast, we identified six significantly enriched pathways
      in the Dongxiang Blue-shelled chicken that are related to amino acid and lipid
      metabolism as well as signal transduction. Our results also reveal the presence
      of a GO term associated with cell metabolism that occurs mainly in the White
      Leghorn breed, while the most significant QTL regions mapped to the Chicken QTL
      Database (GG_4.0) for the Dongxiang Blue-shelled breed are predominantly related
      to lesions, bone mineral content, and other related traits compared to tibia
      length and body weight (i.e., at 14, 28, 42, and 70 d) in the White Leghorn. The
      results of this study highlight differences in growth, immunity, and egg quality
      traits between the two breeds, and provide a foundation for the exploration of
      their genetic mechanisms.

PMID- 29187423
TI  - The Effect of Telemedicine Follow-up Care on Diabetes-Related Foot Ulcers: A
      Cluster-Randomized Controlled Noninferiority Trial.
AB  - OBJECTIVE: To evaluate whether telemedicine (TM) follow-up of patients with
      diabetes-related foot ulcers (DFUs) in primary health care in collaboration with
      specialist health care was noninferior to standard outpatient care (SOC) for
      ulcer healing time. Further, we sought to evaluate whether the proportion of
      amputations, deaths, number of consultations per month, and patient satisfaction
      differed between the two groups. RESEARCH DESIGN AND METHODS: Patients with DFUs
      were recruited from three clinical sites in western Norway (2012-2016). The
      cluster-randomized controlled noninferiority trial included 182 adults (94/88 in
      the TM/SOC groups) in 42 municipalities/districts. The intervention group
      received TM follow-up care in the community; the control group received SOC. The
      primary end point was healing time. Secondary end points were amputation, death,
      number of consultations per month, and patient satisfaction. RESULTS: Using mixed
      effects regression analysis, we found that TM was noninferior to SOC regarding
      healing time (mean difference -0.43 months, 95% CI -1.50, 0.65). When competing
      risk from death and amputation were taken into account, there was no significant
      difference in healing time between the groups (subhazard ratio 1.16, 95% CI 0.85,
      1.59). The TM group had a significantly lower proportion of amputations (mean
      difference -8.3%, 95% CI -16.3%, -0.5%), and there were no significant
      differences in the proportion of deaths, number of consultations, or patient
      satisfaction between groups, although the direction of the effect estimates for
      these clinical outcomes favored the TM group. CONCLUSIONS: The results suggest
      that use of TM technology can be a relevant alternative and supplement to usual
      care, at least for patients with more superficial ulcers.

PMID- 29187422
TI  - Dependency of Heterochromatin Domains on Replication Factors.
AB  - Chromatin structure regulates both genome expression and dynamics in eukaryotes,
      where large heterochromatic regions are epigenetically silenced through the
      methylation of histone H3K9, histone deacetylation, and the assembly of
      repressive complexes. Previous genetic screens with the fission yeast
      Schizosaccharomyces pombe have led to the identification of key enzymatic
      activities and structural constituents of heterochromatin. We report here on
      additional factors discovered by screening a library of deletion mutants for
      silencing defects at the edge of a heterochromatic domain bound by its natural
      boundary-the IR-R+ element-or by ectopic boundaries. We found that several
      components of the DNA replication progression complex (RPC), including
      Mrc1/Claspin, Mcl1/Ctf4, Swi1/Timeless, Swi3/Tipin, and the FACT subunit Pob3,
      are essential for robust heterochromatic silencing, as are the ubiquitin ligase
      components Pof3 and Def1, which have been implicated in the removal of stalled
      DNA and RNA polymerases from chromatin. Moreover, the search identified the
      cohesin release factor Wpl1 and the forkhead protein Fkh2, both likely to
      function through genome organization, the Ssz1 chaperone, the Fkbp39 proline cis
      trans isomerase, which acts on histone H3P30 and P38 in Saccharomyces cerevisiae,
      and the chromatin remodeler Fft3. In addition to their effects in the mating-type
      region, to varying extents, these factors take part in heterochromatic silencing
      in pericentromeric regions and telomeres, revealing for many a general effect in
      heterochromatin. This list of factors provides precious new clues with which to
      study the spatiotemporal organization and dynamics of heterochromatic regions in
      connection with DNA replication.

PMID- 29187424
TI  - Optimising Selenium for Modulation of Cancer Treatments.
AB  - Selenium is an essential trace element involved in many biological processes that
      are mediated through, at least, 25 selenoproteins expressed in humans. Extensive
      study of selenium compounds has demonstrated growth inhibition of malignant cells
      in a vast array of experimental models. Moreover combining selenium with
      conventional cancer therapy has yielded promising results in both preclinical
      studies and a cohort of human trials. The aim of this review is to highlight the
      current research evaluating the role of selenium compounds in combination with
      chemotherapy and radiation. Pharmacodymanic mechanisms responsible for the
      differential effects of the commonly studied compounds on healthy and malignant
      cells are presented and the pertinent in vitro and in vivo data summarised. The
      clinical utility of this approach is discussed both in terms of anti-tumour
      efficacy and toxicity prevention. Finally a case is made for novel trial designs
      to facilitate rapid progression into pivotal studies.

PMID- 29187426
TI  - 18F-Fdg-PET-guided Planning and Re-Planning (Adaptive) Radiotherapy in Head and
      Neck Cancer: Current State of Art.
AB  - BACKGROUND/AIM: A review of the literature is proposed as a contribution to
      current knowledge on technical, physical, and clinical issues about PET-guided
      planning and re-planning radiotherapy (RT) in head and neck cancer. MATERIALS AND
      METHODS: PubMed and Scopus electronic databases were searched for articles
      including clinical trials. Search terms were "gross tumor volume (GTV)
      delineation", "head and neck cancer", "radiotherapy", "adaptive radiotherapy" in
      combination with "PET". RESULTS: A 18F-FDG-PET and CT-scan comparison in GTV
      definition for RT planning of head and neck cancer was shown in twenty-seven
      clinical trials with a total of 712 patients. Only two clinical trials focused on
      PET-guided adaptive radiotherapy (ART) with a total of 31 patients. CONCLUSION:
      18F-FDG-PET is able to achieve an accurate and precise definition of GTV
      boundaries during RT planning, especially in combination with CT-scan. ART
      strategies are proposed to evaluate tumor volume changes, plan boost irradiation
      on metabolically active residual neoplasm and protect organs at risk (OaRs).

PMID- 29187425
TI  - MiRNA-210: A Current Overview.
AB  - microRNAs (miRNAs) are a group of highly conserved small non-coding RNAs that
      were found to enhance mRNA degradation or inhibit post-transcriptional
      translation. Accumulating evidence indicates that miRNAs contribute to
      tumorigenesis and cancer metastasis. microRNA-210 has been largely studied in the
      past several years and has been identified as a major miRNA induced under
      hypoxia. A variety of miR-210 targets have been identified pointing to its role,
      not only in mitochondrial metabolism, but also in angiogenesis, the DNA damage
      response, cell proliferation, and apoptosis. Based on earlier research findings,
      this review aims to provide a current overview on the involvement of miRNA-210 in
      biological processes and diseases.

PMID- 29187427
TI  - The Role of the Androgen Receptor Signaling in Breast Malignancies.
AB  - Breast cancer (BrCa) is the most common malignancy among women worldwide, and one
      of the leading causes of cancer-related deaths in females. Despite the
      development of novel therapeutic modalities, triple-negative breast cancer (TNBC)
      remains an incurable disease. Androgen receptor (AR) is widely expressed in BrCa
      and its role in the disease may differ depending on the molecular subtype and the
      stage. Interestingly, AR has been suggested as a potential target candidate in
      TNBC, while sex hormone levels may regulate the role of AR in BrCa subtypes. In
      the presence of estrogen receptor alpha (ERa), AR may antagonize the ERalpha
      induced effects, whereas in the absence of estrogens, AR may act as an ERalpha
      mimic, promoting tumor. Thus, depending on the BrCa micro-environment, both
      agonists and antagonists of the AR have been suggested as therapeutic approaches.
      Herein, we review the role of AR signaling in BrCa and the molecular cross-talk
      mechanisms with other molecules/pathways, as well as its therapeutic implications
      in the different subtypes of the disease.

PMID- 29187428
TI  - Clinical, Histopathological and Cytogenetic Prognosticators in Uveal Melanoma - A
      Comprehensive Review.
AB  - Uveal melanoma is the most prevalent primary intraocular cancer in adults.
      Although it accounts for only 5% of all melanomas, it is responsible for 13% of
      deaths due to this type of cancer. A wide variety of therapeutic options of
      primary tumor is available and progress in its management is noticeable. The fact
      still remains, however, that almost half of patients develop metastases which may
      be due to practically undetectable cancer spread present as early as at diagnosis
      of the primary focus. Metastatic disease is uniformly fatal despite systemic
      therapy. Prediction of metastasis is crucial for prognosis. It also allows
      targeting of emerging new therapeutic methods to the appropriate group of
      patients. The Authors reviewed literature concerning epidemiology and
      etiopathogenesis of uveal melanoma, and its clinical, histopathological and
      cytogenetic prognosticators.

PMID- 29187429
TI  - Risk Factors for Cytomegalovirus Infection After Allogeneic Hematopoietic Cell
      Transplantation in Malignancies: Proposal for Classification.
AB  - AIM: To identify and classify risk factors for cytomegalovirus (CMV) infection
      and disease in patients receiving allogeneic hematopoietic stem cell
      transplantation (allo-HSCT), treated mainly for acute leukemia. MATERIALS AND
      METHODS: A literature search was performed;eligible trials were clinical studies
      assessing the risk factors for CMV infection or disease in multivariate analysis.
      RESULTS: Early reactivation in the setting of allo-HSCT took place mainly in
      patients without CMV prophylaxis, while late reactivation mainly in those
      patients who had completed previous prophylaxis or were on anti-CMV strategy
      based on pre-emptive prophylaxis. We propose classifying risk factors for CMV
      reactivation and CMV disease in patients after allo-HSCT as major and minor ones.
      Three major risk factors for CMV reactivation and CMV disease were found: (i) CMV
      negative donor CMV-positive recipient serostatus, (ii) acute or chronic graft
      versus-host disease, and (iii) unrelated or mismatched donor. CONCLUSION: CMV
      reactivation should be regarded as a continuous function of recipient and donor
      CMV-seropositivity and recipient immune suppression, caused by conditioning,
      immunosuppressive therapy and human leukocyte antigen disparity between donor and
      recipient.

PMID- 29187430
TI  - The "Yin and Yang" of Platelet-rich Plasma in Breast Reconstruction After
      Mastectomy or Lumpectomy for Breast Cancer.
AB  - Surgery remains the mainstay of treatment for breast cancer, including complete
      or partial mastectomy and lumpectomy. Breast reconstruction has gained popularity
      mainly due to its tremendous impact on the psychological status of the patients.
      Autologous fat grafting is a well-established method used in cosmetic surgery;
      however, fat re-absoprtion, fat necrosis, calcifications and oil-cyst formation
      are some usually encountered complications limiting the efficacy of this
      approach. Platelet-rich plasma (PRP) has recently been postulated as a promising
      method for tissue regeneration since it contains high levels of diverse human
      growth factors. To date, preliminary results from clinical studies regarding the
      combination of PRP and fat grafting in breast reconstruction have shown ambiguous
      results, whereas preclinical studies are more favorable. However, concerns have
      been raised regarding the extent of cellular promotion induced by PRP application
      and the corresponding potential malignant transformation. The aim of our study
      was to present, analyze and critically evaluate the role of PRP in breast
      reconstruction after breast cancer surgery in terms of efficacy and oncological
      safety highlighting the caution that needs to be taken in order to eliminate any
      chance of recurrence in patients who have theoretically undergone complete
      excision of the tumor burden.

PMID- 29187431
TI  - Microsatellite Instability as a Prognostic Factor in Stage II Colon Cancer
      Patients, a Meta-Analysis of Published Literature.
AB  - BACKGROUND/AIM: The prognostic role of microsatellite instability (MSI) in stage
      II colon cancer patients remains controversial despite the fact that it has been
      investigated in a number of studies. Hazard ratios differ considerably among
      these studies. We performed a meta-analysis to define the significance of MSI in
      this group of patients. MATERIALS AND METHODS: Studies indexed in PubMed
      presenting separate data on MSI status and survival outcomes for stage II colon
      cancer patients have been analyzed using fixed-effect meta-analysis of hazard
      ratio (HR) according to the method of Peto. RESULTS: Analysis was performed on 19
      studies including 5,998 patients. A 47.3% of patients received postoperative
      chemotherapy and included 52.8% males and 47.2% females. Eight studies included
      some rectal cancer patients although this cohort was not clearly defined in 3 of
      these. MSI observed in 20.8% (mean) of patients (median 19.9%). HR for overall
      survival (OS) of MSI vs. microsatellite stable (MSS) tumors for the entire
      population: 0.73 (95% confidence interval (CI)=0.33-1.65); HR for disease-free
      survival (DFS):0.60 (95%CI=0.27-1.32). No statistical significant difference was
      found when studies analyzing MSI with genotyping (MG) and immunohistochemistry
      (IHC) were compared separately (MG vs. IHC: HR OS 0.45, 95%CI=0.10-2.05 vs. 0.95,
      95%CI=0.57-1.58; HR DFS 0.51, 95%CI=0.14-1.85 vs. 0.67, 95%CI=0.26-1.70).
      However, numerically MSI determination with genotyping shows significantly lower
      hazard ratios for both DFS and OS. Separate analysis of studies describing colon
      cancer patients only showed HR OS 0.72 (95%CI=0.31-1.71); HR DFS 0.60 (95%CI=0.27
      1.31). CONCLUSION: No significant relation was found between MSI status and OS or
      DFS. Routine determination of MSI status to guide postoperative management of
      stage II colon cancer patients cannot be recommended. New large scale high
      quality studies are needed to answer this question definitively, since currently
      analyzed studies vary considerably.

PMID- 29187432
TI  - Paclitaxel, Carboplatin and 1,25-D3 Inhibit Proliferation of Endometrial Cancer
      Cells In Vitro.
AB  - BACKGROUND/AIM: Endometrial cancer cells are known to be sensitive to carboplatin
      and paclitaxel. Furthermore, vitamin D (1,25-D3) has been reported to inhibit
      endometrial cancer cell growth both as a single agent and combined with
      carboplatin. However, there are no studies comparing the effect of paclitaxel and
      carboplatin as single agents vs. in combination in endometrial cancer cell lines.
      Neither has the effect of 1,25-D3 been studied with paclitaxel. The present study
      investigated the effect of paclitaxel, carboplatin and 1,25-D3 on the growth of
      endometrial cancer cells in vitro. MATERIALS AND METHODS: Two endometrial
      adenocarcinoma cell lines (UT-EC-1 and UT-EC-3) were cultured with different
      doses of paclitaxel, carboplatin and 1,25-D3. The cellular VDR (vitamin D
      receptor) mRNA levels were measured and the expression of estrogen (ER) and
      progesterone (PR) receptors by the cells was determined. RESULTS: In the UT-EC-1
      cell line the growth inhibition was 72% with paclitaxel, 54% with carboplatin and
      73% with the combination of these compounds. The corresponding numbers in UT-EC-3
      were 70%, 33% and 65%, respectively. 1,25-D3 suppressed cell growth 88% with
      paclitaxel, 63% with carboplatin and 87% with their combination in the UT-EC-1
      cell line. CONCLUSION: In both cell lines, single-agent paclitaxel was as
      effective as the combination of the compounds and more effective than single
      carboplatin. 1,25-D3 may further contribute to the cytotoxic effect of these
      agents.

PMID- 29187433
TI  - ESE-1 Knockdown Attenuates Growth in Trastuzumab-resistant HER2+ Breast Cancer
      Cells.
AB  - BACKGROUND/AIM: ESE-1/Elf3 controls transformation properties in mammary
      epithelial cells, and is most clinically relevant in HER2+ breast cancer. Herein
      we showed that ESE-1 knockdown inhibits tumorigenic growth in HER2+, trastuzumab
      resistant HR20 (derived from HER2+ ER+ BT474) and Pool2 (derived from HER2+ ER-
      SKBR3 cells) cell lines. MATERIALS AND METHODS: We used cell proliferation,
      clonogenicity, viability, and soft agar assays to measure the effects of ESE-1
      knockdown in cell lines. RESULTS: ESE-1 knockdown in the resistant cell lines
      inhibited HER2 and other downstream effectors in a cell-type specific manner, but
      caused down-regulation of pAkt and cyclin D1 in both sublines. In parental BT474
      and SKBR3 ESE-1 silencing revealed a potent anti-proliferative effect that mimics
      the trastuzumab-mediated growth inhibition but did not enhance trastuzumab
      sensitivity in the resistant sublines. CONCLUSION: This study provides rationale
      to study ESE-1 as a novel mean to treat HER2+ patients who show resistance to
      anti-HER2 therapy.

PMID- 29187434
TI  - Sensitization of rhTRAIL-resistant Triple-negative Breast Carcinoma Through
      Silibinin Co-Treatment.
AB  - BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is the most fatal form of
      breast cancer due to the shortcomings of therapies. However, recombinant human
      tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is a promising
      anticancer therapeutic that possesses the capability to promote the induction of
      apoptosis in cancer cells, but some TNBCs are resistant to rhTRAIL's pro
      apoptotic effects. Therefore, a combinatorial treatment approach with silibinin
      and rhTRAIL was considered in order to sensitize rhTRAIL-resistant TNBCs.
      MATERIALS AND METHODS: The co-treatment of rhTRAIL and silibinin's impact on
      apoptosis induction in rhTRAIL-resistant TNBC BT-20 and HCC1937 cells was
      inspected via application of Annexin V/PI assays and western blot analysis.
      RESULTS: Silibinin possessed the ability to sensitize the examined rhTRAIL
      resistant TNBC cells to rhTRAIL-induced apoptosis through the up-regulation of
      death receptors 4 and 5 and the down-regulation of survivin transcriptionally.
      CONCLUSION: Silibinin is a good sensitizing agent for rhTRAIL-resistant TNBCs.

PMID- 29187435
TI  - Evaluating Metformin as a Potential Chemosensitizing Agent when Combined with
      Docetaxel Chemotherapy in Castration-resistant Prostate Cancer Cells.
AB  - BACKGROUND/AIM: Docetaxel, the first-line chemotherapy for metastatic castration
      resistant prostate cancer (mCRPC), provides certain survival benefits, but is
      associated with significant toxicity. A novel therapeutic approach for mCRPC is
      combining docetaxel with a chemosensitizing agent. We hypothesized that
      metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC
      cells. MATERIALS AND METHODS: MTS assays were used to determine the effect of
      metformin-docetaxel treatment on PC3 and DU145 cell viability. Wound-healing and
      ATP concentration assays were used to evaluate cell migration and intracellular
      ATP levels following metformin-docetaxel treatment. Western blotting was used for
      mechanistic evaluation. RESULTS: Metformin-docetaxel treatment significantly
      reduced PC3 cell viability. Metformin-docetaxel treatment did not significantly
      affect cell migration or intracellular ATP levels. Western blotting revealed
      metformin-docetaxel treatment did not significantly change AMPK or P-AMPK
      expression patterns. CONCLUSION: Metformin may be an effective chemosensitizer
      for certain types of CRPC cells, but further investigation is needed.

PMID- 29187436
TI  - Identification of CpG Sites of SERPINA5 Promoter with Opposite Methylation
      Patterns in Benign and Malignant Prostate Cells.
AB  - BACKGROUND/AIM: To date there has been no investigation into the epigenetic
      regulation of the serine protease inhibitor SERPINA5 in prostate cancer, where
      lack of this gene was considered to facilitate invasive growth patterns.
      MATERIALS AND METHODS: Methylation degrees of eight CpG sites of SERPINA5 were
      analyzed in normal and malignant prostate cells using nucleotide sequencing,
      methylation-specific high resolution melting and digital droplet PCR techniques.
      RESULTS: The methylation degree of five CpG sites significantly correlated with
      lower SERPINA5 expression levels. In contrast, two CpG sites (at -19 bp and -14
      bp from the transcription start site) were hypermethylated in normal epithelial
      prostate cells, benign hyperplasic cells and low-invasive malignant LNCaP cells,
      whereas in aggressive DU-145 and PC-3 cell lines, these sites were essentially
      unmethylated. CONCLUSION: Novel methylation patterns of two distinct CpG sites of
      the SERPINA5 promoter may be useful for differentiating benign from malignant
      prostate disease.

PMID- 29187437
TI  - Antiproliferative Activity and Induction of Apoptosis in Human Melanoma Cells by
      Houttuynia cordata Thunb Extract.
AB  - BACKGROUND/AIM: To analyze the apoptotic effect of Houttuynia cordata Thunb (HCT)
      extract on human melanoma A375 cells and its underlying mechanisms. MATERIALS AND
      METHODS: The effects of HCT on cell death were determined using the MTT assay.
      Hoechst 33342 staining was conducted to confirm the detection of cell apoptosis.
      Caspase-3 and caspase-8 mRNA and cleaved protein levels were investigated by RT
      PCR and western blotting, respectively. The release of high mobility group box 1
      (HMGB1) and phosphorylation of mitogen-activated protein kinase (MAPK) were
      determined by ELISA. RESULTS: Caspase-3 and caspase-8 specific inhibitors
      suppressed HCT-induced cell death. HCT increased caspase-3 and caspase-8 mRNA,
      protein levels, and caspase activities in a concentration- and time-dependent
      manner. HCT induced MAPK phosphorylation in a time-dependent fashion.
      Pretreatment of cells with a selective inhibitor of p38 MAPK reduced apoptosis
      and reversed the levels of HMGB1 release in response to HCT treatment.
      CONCLUSION: HCT induces A375 programmed cell death by activating the caspase
      dependent pathway and by p38 phosphorylation associated with HMGB1 reduction.

PMID- 29187438
TI  - Functional Characterization of VEGF- and FGF-induced Tumor Blood Vessel Models in
      Human Cancer Xenografts.
AB  - BACKGROUND/AIM: Tumor angiogenesis induced by vascular endothelial growth factor
      (VEGF) and/or fibroblast growth factor (FGF) plays an important role in tumor
      growth, metastasis, and drug resistance. However, the characteristics of tumor
      vessels derived from these angiogenic factors have not been fully explored.
      MATERIALS AND METHODS: To functionally examine tumor vessels, we developed in
      vivo VEGF- and FGF-induced tumor blood vessel models. We performed
      immunohistochemistry and Hoechst perfusion assay to elucidate histopathological
      differences between the derived tumor vessels. To kinetically understand tumor
      perfusion, we employed radiolabeled PEGylated liposomes. RESULTS: While tumor
      vessel density was substantially increased by enhanced expression levels of VEGF
      and FGF, permeability of VEGF-driven tumor vessels was significantly higher than
      that of FGF-driven ones, the latter demonstrating an increased number of pericyte
      covered vessels. Accordingly, we observed an increased tumor retention of the
      PEGylated liposomes in the VEGF-driven tumor. CONCLUSION: Our in vivo models of
      tumor vessel demonstrate the frequency of pericyte coverage and tumor perfusion
      levels as major functional differences between VEGF- and FGF-driven tumor
      vessels.

PMID- 29187439
TI  - Expression of FAS-L Differs from Primary to Relapsed Low-grade Gliomas and
      Predicts Progression-free Survival.
AB  - BACKGROUND/AIM: The tumor necrosis factor FAS is overexpressed in high-grade
      gliomas (HGG). Only little is known about FAS or FAS ligand (FAS-L) in low-grade
      gliomas (LGG). We explored FAS/FAS-L expression in LGG, focusing on differences
      in primary and relapsed LGG and on its prognostic value. PATIENTS AND METHODS: A
      total of 133 glioma samples (73 LGG, 60 HGG) were collected. The LGG samples
      included 15 matched pairs of primary and relapsed tumors. RT-PCR was performed to
      measure FAS/FAS-L expression, using subunit A, flavoprotein variant (SDHA) as
      housekeeper. Clinical data included progression free- (PFS) and overall survival
      (OS). RESULTS: LGG showed significantly lower FAS but higher FAS-L expression
      than HGG. The FAS-L expression was higher in primary compared to relapsed LGG and
      had a positive prognostic value concerning PFS (median 45.20 vs. 31.37 months).
      CONCLUSION: FAS-L could act as a prognostic marker and potential target in
      primary LGG.

PMID- 29187440
TI  - Liprin-alpha4 as a Possible New Therapeutic Target for Pancreatic Cancer.
AB  - BACKGROUND/AIM: In pancreatic cancer, where the microenvironment is extremely
      hypoxic, analyzing signal transduction under hypoxia is thought to be
      significantly important. By investigating microarray analysis of pancreatic
      cancer cells cultured under both normoxia and hypoxia, we found that the
      expression of leukocyte common antigen-related (LAR)-interacting protein (liprin)
      alpha4 was extremely increased under hypoxia compared to under normoxia.
      MATERIALS AND METHODS: In the present study, the biological significance of
      liprin-alpha4 in pancreatic cancer was investigated and whether liprin-alpha4 has
      potential as a therapeutic target for pancreatic cancer was estimated. RESULTS:
      Suppression of liprin-alpha4 reduced proliferation of pancreatic cancer cells
      both in vitro and in vivo. Inhibition of liprin-alpha4 also reduced invasiveness
      through the suppression of endothelial-mesenchymal transition. Stimulation by
      liprin-alpha4 was through phosphoinositide 3-kinase and mitogen-activated protein
      kinase signaling pathways. CONCLUSION: Liprin-alpha4 plays a pivotal role in
      inducing malignant phenotypes such as increased proliferation and invasion in
      pancreatic cancer, and that liprin-alpha4 could be a new effective therapeutic
      target for pancreatic cancer.

PMID- 29187441
TI  - Flavopiridol Strongly Sensitizes Canine Lymphoma Cells to TRAIL-induced
      Apoptosis.
AB  - BACKGROUND/AIM: Targeting the extrinsic apoptotic pathway is an interesting
      option for anticancer therapy. A protein which such ability is Apo2 ligand, also
      known as TNF-related apoptosis-inducing ligand (TRAIL). The aim of this study was
      to examine the possibility of sensitizing resistant CLBL-1 canine lymphoma cells
      to TRAIL-induced apoptosis by using flavopiridol (FVP) a cyclin-dependent kinase
      inhibitor (CDKs). MATERIALS AND METHODS: The CLBL-1 (canine B-cell lymphoma cell
      line) was used in the study. The effect of FVP and TRAIL treatment on apoptosis
      induction was assessed by flow cytometry and western blot. RESULTS: Although
      canine lymphoma cells were resistant to TRAIL-induced apoptosis, combination of
      this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1
      lymphoma cells. CONCLUSION: Our results demonstrated that although canine
      lymphoma cells were resistant to TRAIL-induced apoptosis, combination of this
      death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma
      cell line. Although further investigation is required to deepen the knowledge of
      TRAIL as an antitumor agent in canine cancers, our results open the door to
      future use of TRAIL-based treatment strategies in veterinary oncology.

PMID- 29187442
TI  - Updated Histologic Classification of Adenomas and Carcinomas in the Colon of
      Carcinogen-treated Sprague-Dawley Rats.
AB  - BACKGROUND: Recent studies have disclosed novel histological phenotypes of colon
      tumours in carcinogen-treated rats. The aim of this study was to update the
      current histological classification of colonic neoplasias in Sprague-Dawley (SD)
      rats. MATERIALS AND METHODS: Archival sections from 398 SD rats having 408
      neoplasias in previous experiments were re-evaluated. RESULTS: Of the 408 colonic
      neoplasias, 11% (44/408) were adenomas without invasive growth and 89% (364/408)
      invasive carcinomas. Out of the 44 adenomas, 82% were conventional (tubular or
      villous), 14% traditional serrated (TSA; with unlocked serrations or with closed
      microtubules) and 5% gut-associated lymphoid tissue (GALT)-associated adenomas.
      Out of 364 carcinomas, 57% were conventional carcinomas, 26% GALT carcinomas, 8%
      undifferentiated, 6% signet-ring cell carcinomas, and 4% traditional serrated
      carcinomas (TSC). Thus, conventional adenomas, conventional carcinomas and GALT
      associated carcinomas predominated (p<0.05). CONCLUSION: The updated
      classification of colonic tumours in SD rats includes conventional adenomas, TSA,
      GALT-associated adenomas, conventional carcinomas, TSC, GALT-associated
      carcinomas, signet-ring cell carcinomas and undifferentiated carcinomas. Several
      of the histological phenotypes reported here are not included in any of the
      current classifications of colonic tumours in rodents. This updated
      classification fulfils the requirements for an animal model of human disease,
      inasmuch as similar histological phenotypes of colon neoplasias have been
      documented in humans.

PMID- 29187443
TI  - Total Knockdown of LMW-PTP in MDA-MB-231 Cells Reduces Osteoclastogenesis.
AB  - BACKGROUND: Low molecular weight protein tyrosine phosphatase (LMW-PTP) has been
      related to tumorigenesis, having both oncogenic and anti-oncogenic roles. The
      differential roles of its main active isoforms (fast and slow) may account for
      these discrepancies. The fast isoform has been described to be involved in the
      bone-metastatic process, although knockdown of the slow isoform was recently
      reported to reduce osteoclastogenesis. We aimed to study the influence of LMW-PTP
      isoforms on osteoclast differentiation. MATERIALS AND METHODS: Osteoclast
      precursors (RAW 264.7) were cultured with conditioned medium from MDA-MB-231
      breast cancer cells with total knockdown of LMW-PTP and with knockdown of the
      slow isoform of LMW-PTP. Tartarate-resistant acid phosphatase (TRAP) staining and
      quantification were performed to assess osteoclast differentiation. RESULTS:
      Total knockdown of LMW-PTP, but not of slow LMW-PTP significantly reduced
      osteoclast differentiation of RAW 264.7 cells. CONCLUSION: We suggest that total
      LMW-PTP increases osteoclastic differentiation, albeit not at the expense of the
      slow isoform.

PMID- 29187444
TI  - Contribution of Matrix Metalloproteinase-7 Genotypes to the Risk of Non-solid
      Tumor, Childhood Leukemia.
AB  - BACKGROUND/AIM: The matrix metalloproteinases (MMPs) are important in
      inflammation and carcinogenesis, and the genotypic role of MMP7 has never been
      examined in leukemia to date. Therefore, in this study we aimed to evaluate the
      contribution of the genotypic variants in the promoter region of MMP7 (A-181G and
      C-153T) to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. MATERIALS
      AND METHODS: In this case-control study, 266 patients with childhood ALL and 266
      non-cancer controls were genotyped by polymerase chain reaction-restriction
      fragment length polymorphism methodology. RESULTS: The distribution of AA, AG and
      GG for MMP7 promoter A-181G genotype was 83.5, 12.0 and 4.5% in the childhood ALL
      group and 89.8%, 9.4 and 0.8% in the non-cancer control group, respectively (p
      for trend=0.0134), significantly differentially distributed between childhood ALL
      and control groups. The comparisons in allelic frequency distribution also
      support the findings that G appears to be the risky allele in childhood ALL. In
      genotype and gender interaction analysis, it was found that boys carrying the
      MMP7 A-181G GG and AG+GG genotypes had 9.05- and 2.45-fold odds ratios (ORs)
      (p=0.0135 and 0.0142, respectively) for childhood ALL compared to those carrying
      wild-type AA genotype. But these differences were not found in girls. Analysis of
      genotype interaction with age of onset age showed those aged less than 3.5 years
      at onset carrying the GG or AG+GG genotypes also had elevated ORs of 8.79- and
      2.04-fold (p=0.0150 and 0.0413, respectively) for childhood ALL, but there was no
      such difference for those having an age at onset of 3.5 years or more.
      CONCLUSION: Our results indicate that the MMP7 A-181G genotype interacts with age
      and gender and may serve as an early and predictive biomarker for childhood ALL.

PMID- 29187445
TI  - The Contrasting Role of the Mediator Subunit MED30 in the Progression of Bladder
      Cancer.
AB  - BACKGROUND/AIM: The Mediator complex is a key regulator of gene transcription,
      and several studies have demonstrated altered expression of particular subunits
      in diverse human diseases, especially cancer. To date, nothing is known about the
      role of MED30 in bladder cancer. MATERIALS AND METHODS: We, therefore, performed
      an RNA expression and survival analysis of the subunit MED30 in 537 samples of
      bladder cancer by using the database cBioPortal. To validate these data on the
      protein level, we practiced immunohistochemical staining against MED30 on a
      tissue microarray containing 210 samples of all tumour stages and performed
      survival analyses. For functional analysis, the siRNA-mediated knockdown of MED30
      was performed in the cell lines T24 and TCCSUP followed by proliferation,
      migration, and invasion assays. RESULTS: On the mRNA and protein levels, higher
      expression of MED30 is associated with better patient survival. In accordance
      with this, advanced T- and N-stages showed lower expression of MED30. In
      contrast, knockdown of MED30 led to reduction of the tumour parameters
      proliferation, migration, and invasion in the BCa cell lines. CONCLUSION: MED30
      appears to be integrated in the progression of the urothelial tumour in the
      bladder.

PMID- 29187446
TI  - TP53 Mutation Status of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma
      with a Wild-type p53 Immunostaining Pattern.
AB  - BACKGROUND/AIM: Diffuse and strong nuclear p53 immunoreactivity and a complete
      lack of p53 expression are regarded as indicative of missense and nonsense
      mutations, respectively, of the TP53 gene. Tubo-ovarian and peritoneal high-grade
      serous carcinoma (HGSC) is characterized by aberrant p53 expression induced by a
      TP53 mutation. However, our experience with some HGSC cases with a wild-type p53
      immunostaining pattern led us to comprehensively review previous cases and
      investigate the TP53 mutational status of the exceptional cases. MATERIALS AND
      METHODS: We analyzed the immunophenotype of 153 cases of HGSC and performed TP53
      gene sequencing analysis in those with a wild-type p53 immunostaining pattern.
      RESULTS: Immunostaining revealed that 109 (71.3%) cases displayed diffuse and
      strong p53 expression (missense mutation pattern), while 39 (25.5%) had no p53
      expression (nonsense mutation pattern). The remaining five cases of HGSC showed a
      wild-type p53 immunostaining pattern. Direct sequencing analysis revealed that
      three of these cases harbored nonsense TP53 mutations and two had novel splice
      site deletions. CONCLUSION: TP53 mutation is almost invariably present in HGSC,
      and p53 immunostaining can be used as a surrogate marker of TP53 mutation. In
      cases with a wild-type p53 immunostaining pattern, direct sequencing for TP53
      mutational status can be helpful to confirm the presence of a TP53 mutation.

PMID- 29187447
TI  - Analysis of Autoantibodies Related to Tumor Progression in Sera from Patients
      with High-grade Non-muscle-invasive Bladder Cancer.
AB  - BACKGROUND/AIM: Bladder cancer (BC) has a high recurrence rate and may progress
      to being a muscle-invasive lesion, that is potentially associated with a poor
      prognosis. We identified tumor-associated proteins that were recognized by
      autoantibodies in sera from patients with high-grade non-muscle-invasive bladder
      cancer (HG-NMIBC) by proteomic analysis. MATERIALS AND METHODS: The serum levels
      of these autoantibodies against identified proteins were validated by dot blot
      analysis with sera from 95 patients with BC and 35 healthy controls. The
      expression of identified proteins was immunohistochemically analyzed in 115 BC
      tissues. RESULTS: Autoantibody against protein phosphatase 1, catalytic subunit,
      alpha isoform (PPP1CA) protein was detected in pretreated sera from patients with
      HG-NMIBC who showed progression. The serum IgG level of anti-PPP1CA autoantibody
      was significantly correlated with pathological stage, grade, lymphovascular
      invasion, and prognosis. The immunoreactions for PPP1CA protein in BC was
      significantly correlated with pathological stage, grade, and lymphovascular
      invasion. CONCLUSION: PPP1CA is a candidate sero-diagnostic and prognostic marker
      for patients with BC.

PMID- 29187448
TI  - Potential Roles of GLUT12 for Glucose Sensing and Cellular Migration in MCF-7
      Human Breast Cancer Cells Under High Glucose Conditions.
AB  - BACKGROUND/AIM: Recent reports have indicated that hyperglycaemia is associated
      with breast cancer progression. High glucose conditions corresponding to
      hyperglycaemia significantly promote migration of MCF-7 human breast cancer
      cells, however, little is known about the mechanisms of glucose sensing for the
      acquisition of migratory properties by MCF-7 cells. This study investigated
      glucose sensing and mediation, which are responsible for the high motility of MCF
      7 cells. MATERIALS AND METHODS: We evaluated the migration of MCF-7 cells
      cultured in high glucose-containing medium and essential regulatory factors from
      the perspective of the glucose transport system. RESULTS: We demonstrated that
      glucose transporter 12 (GLUT12) protein level increased in MCF-7 cells and co
      localized with actin organization under high glucose conditions. Moreover, GLUT12
      knockdown completely abrogated high glucose-induced migration, indicating that
      GLUT12 functionally participates in sensing high glucose concentrations.
      CONCLUSION: GLUT12 plays a critical role in the model of breast cancer
      progression through high glucose concentrations.

PMID- 29187449
TI  - High STAT4 Expression Indicates Better Disease-free Survival in Patients with
      Gastric Cancer.
AB  - BACKGROUND: The aim of this study was to investigate the significance of signal
      transducer and activator of transcription 4 (STAT4) expression and the
      correlation between STAT4 and interferon gamma (IFN-gamma) in patients with
      gastric cancer. PATIENTS AND METHODS: Sixty-two patients who underwent
      gastrectomy for gastric cancer were enrolled in the study. STAT4 and IFNG mRNA
      expression was evaluated by quantitative real-time polymerase chain reaction
      (PCR). Immunohistochemistry was performed to examine CD8+ T-cells, and STAT4 and
      IFN-gamma expression. RESULTS: STAT4 mRNA expression was significantly correlated
      with IFNG mRNA expression (p<0.05). Regarding disease-free survival, there was a
      significant difference between the groups with high and low STAT4 expression (5
      year disease-free survival: 77.8% and 56.4%, p<0.05). Univariate analysis
      revealed that tumor differentiation and STAT4 expression were significant factors
      for tumor recurrence. CONCLUSION: High expression of STAT4 in gastric cancer
      predicted a better clinical outcome. STAT4 might be a useful biomarker to
      identify patients at high risk of recurrence after gastrectomy.

PMID- 29187450
TI  - Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis.
AB  - BACKGROUND: Sonic hedgehog (SHH) signaling is related to the pathogenesis of oral
      squamous cell carcinoma (OSCC), but its role in OSCC is not yet well understood.
      In this study, we analyzed the role of SHH signaling in OSCC. MATERIALS AND
      METHODS: We examined the expression pattern of SHH and its signal proteins in
      clinically resected OSCC samples by immunohistochemistry. We also evaluated the
      function of SHH signaling using the hedgehog signaling inhibitor cyclopamine in
      vivo and in vitro by proliferation, migration and angiogenesis analyses. RESULTS:
      We found that SHH was highly expressed in human tongue OSCC, whereas patched
      (PTCH1), glioma-associated oncogene 1 (GLI1) and GLI2 proteins were expressed in
      the microvascular cells in the tumor invasive front. Administration of
      cyclopamine to mice suppressed the growth and angiogenesis of OSCC xenografts in
      vivo. Moreover, cyclopamine inhibited endothelial cell proliferation and
      migration, and reduced aorta vascular length in the rat. CONCLUSION: These
      findings suggest that OSCC-derived SHH stimulates angiogenesis at the tumor
      invasive front.

PMID- 29187451
TI  - Cold Atmospheric Plasma (CAP) and CAP-Stimulated Cell Culture Media Suppress
      Ovarian Cancer Cell Growth - A Putative Treatment Option in Ovarian Cancer
      Therapy.
AB  - BACKGROUND/AIM: Ovarian cancer (OC) is a gynecologic tumor with poor prognosis.
      Despite radical cytoreductive surgery and platinum-based adjuvant systemic
      treatment, OC will relapse in the majority of the cases. Thus, cold atmospheric
      plasma (CAP), a highly reactive physical state bearing diverse biological
      activities being suited for anticancer therapy, may be a promising option in OC
      therapy. MATERIALS AND METHODS: OC cell lines were exposed either directly to the
      CAP or to cell culture medium previously exposed to CAP. Cell proliferation and
      cell motility was measured. RESULTS: The data demonstrated, that even a single
      application of a short-term CAP treatment led to an attenuation of OC cell growth
      and motility. Moreover, incubation with CAP-treated cell culture medium gave
      similar effects. Results were consistent in four OC cell lines. CONCLUSION: In
      summary, the CAP application in oncological surgery leads to strong anti
      proliferative effects and opens up novel opportunities for the OC treatment.

PMID- 29187452
TI  - Y-box Binding Protein-1 Enhances Oncogenic Transforming Growth Factor beta
      Signaling in Breast Cancer Cells via Triggering Phospho-Activation of Smad2.
AB  - BACKGROUND/AIM: Transforming growth factor beta (TGFbeta) plays a role in diverse
      oncogenic pathways including cell proliferation and cell motility and is
      regulated by the pleiotropic factor Y-box binding protein-1 (YB-1). In breast
      cancer, Sma/Mad related protein 2 (Smad2) represents the most common downstream
      transducer in TGFbeta signaling. MATERIALS AND METHODS: Here, YB-1's impact on
      Smad2 phospho-activation was characterized by incubation of the breast cancer
      cell line MCF-7 with or without TGFbeta1 in the absence or presence of
      overexpressed YB-1 protein. The phospho-status of Smad2 was assessed via western
      blotting. RESULTS: Analysis of MCF-7 cells revealed no induction of total Smad2
      neither in the presence of TGFbeta1, nor during YB-1 overexpression. In contrast,
      incubation with TGFbeta1 led to an increase of phosphorylated Smad2 forms which
      was significantly amplified by simultaneously overexpressed YB-1 (2.8+/-0.2
      fold). CONCLUSION: Oncogenic YB-1 indirectly enhances TGFbeta signaling cascades
      via Smad2 phospho-activation and may represent a promising factor for future
      diagnosis and therapy of breast cancer.

PMID- 29187453
TI  - Evaluation of the Effects of Aminonaphthoquinone Derivatives in Combination with
      Curcumin Against ER-positive Breast Cancer and Related Tumours.
AB  - BACKGROUND/AIM: Combination therapies are often explored to treat cancer. The use
      of curcumin as an adjuvant to current chemotherapies has been reported, whilst
      aminonaphthoquinones have shown potential as anticancer agents in various tumour
      cell lines. This study aimed at screening synthetic aminonathoquinone derivatives
      (Rau 008, Rau 010, Rau 015 and Rau 018) alone and in combination with curcumin
      for anti-breast cancer activity. MATERIALS AND METHODS: Combination effects were
      determined in MCF-7 breast cancer cells using combination index analyses.
      Synergistic anti-proliferative effects were further investigated in breast (MCF
      7, MDA-MB-231), osteosarcoma (MG-63) and endometrial (HEC-1A) cancer-derived
      cells. RESULTS: Rau 015 (15 MUM) and curcumin (112.5 MUM) significantly reduced
      MCF-7, MDA-MB-231 and MG-63 cell proliferation compared to individual treatment,
      indicating synergistic anti-proliferative effects. Rau 018 (30 MUM) and curcumin
      (100 MUM) displayed similar effects in MCF-7 and MG-63 cells. CONCLUSION: We
      report on the potential of Rau 015 or Rau 018 as anti-breast cancer agents when
      combined with curcumin.

PMID- 29187454
TI  - P-gp Inhibition by XL019, a JAK2 Inhibitor, Increases Apoptosis of Vincristine
      treated Resistant KBV20C Cells with Increased p21 and pH2AX Expression.
AB  - The present study was designed to identify conditions that could increase the
      sensitivity of resistant cancer cells to antimitotic drugs. We investigated
      whether a Janus kinase 2 (JAK2) inhibitor used in clinical trials, XL019,
      sensitizes antimitotic drug-resistant KBV20C cells. XL019 reduced cellular
      viability and increased apoptosis in vincristine-treated KBV20C cells,
      independently of the JAK/signal transducer and activator of transcription (STAT)
      pathway. Based on the ATP-binding cassette protein B1 [ABCB1, P-glycoprotein (P
      gp)] inhibitory assay, we demonstrated that XL019 functions as a P-gp inhibitor
      in drug-resistant KBV20C cells. Considering that another JAK2 inhibitor, CEP
      33779, also inhibited P-gp and sensitized drug-resistant cancer cells in a
      previous study, we concluded that JAK2 inhibitors can be used as P-gp inhibitors
      in drug-resistant cancer cells. Fluorescence-activated cell sorting, western
      blot, and annexin V analyses were used to further investigate the mechanism of
      action of XL019 in vincristine-treated KBV20C cells. XL019 induced early
      apoptosis of KBV20C cells in response to vincristine treatment via increased G2
      phase arrest. Moreover, G2 phase arrest and apoptosis of cells co-treated with
      vincristine and XL019 resulted from the up-regulation of phosphorylated
      retinoblastoma protein (pRb), p21, and the DNA-damage protein, phosphorylated H2A
      histone family, member X (pH2AX). Additionally, the P-gp-inhibitory effect of
      XL019 was less than that of CEP-33779, and a more than 2-fold higher dose was
      required to sensitize vincristine-treated KBV20C cells. Furthermore, lower doses
      of XL019 were required to sensitize KBV20C cells to a degree similar to that
      obtained with the established P-gp inhibitor verapamil, suggesting that XL019 has
      higher specificity than verapamil. Our results showed that JAK2 inhibitors
      inhibited P-gp action via a direct binding mechanism, which was similar to that
      of verapamil. These findings indicate that JAK2 inhibitors may be promising
      therapeutics for the treatment of cancer that is resistant to antimitotic drugs.

PMID- 29187455
TI  - Comparison of PD-L1 mRNA Expression Measured with the CheckPoint Typer(r) Assay
      with PD-L1 Protein Expression Assessed with Immunohistochemistry in Non-small
      Cell Lung Cancer.
AB  - BACKGROUND: Immunohistochemical (IHC) assessment of programmed death-ligand 1 (PD
      L1) in non-small cell lung cancer (NSCLC) has become important since the
      development of anti-PD-1/-PD-L1 directed drugs. Various PD-L1 antibodies and cut
      offs have been used in different trials to predict response to these drugs, thus
      comparison of those studies is difficult. We compared PD-L1 mRNA expression
      measured by RT-qPCR with PD-L1 protein expression evaluated by IHC. Moreover, we
      investigated the impact of different tumour tissue acquisition methods on the
      reliability of PD-L1 measurement techniques. MATERIALS AND METHODS: NSCLC cases
      (N=22), including n=9 mediastinal lymph node biopsies acquired by endobronchial
      ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and n=5
      metastases, were evaluated prospectively for PD-L1 protein on tumor cells (TC)
      and immune cells (IC) using E1L3N and 28-8 antibodies and PD-L1 mRNA using the
      CheckPoint TYPER(r) assay. RESULTS: In primary NSCLC tissues, agreement between
      PD-L1 mRNA and TC staining using the 28-8 antibody was excellent (K=0.85,
      p=0.0002). Comparing both PD-L1 antibodies against each other showed a kappa
      value of 0.58 (p=0.0106). In EBUS-TBNA, PD-L1 mRNA correlated perfectly with the
      28-8 antibody (K=1.0, p=0.0023). PD-L1 mRNA levels significantly differed when
      comparing 28-8 TC staining of tumours >49% with 1-49% and 0% (p=0.0040; p=0.0081,
      respectively). In metastatic lesions, differences between PD-L1 mRNA and IHC
      became apparent (K=0.2, p=0.2525). CONCLUSION: Testing of PD-L1 mRNA and 28-8 IHC
      showed an excellent agreement in NSCLC samples including mediastinal lymph node
      biopsies. Since PD-L1 expression in >50% TC detected by 28-8 IHC can be reliably
      detected by RT-qPCR, quantitative PD-L1 mRNA determination should be considered
      as an alternative to IHC as there is no interobserver variability in RNA results.

PMID- 29187456
TI  - Analysis of the miRNA Profiles of Melanoma Exosomes Derived Under Normoxic and
      Hypoxic Culture Conditions.
AB  - BACKGROUND/AIM: MicroRNAs (miRNAs) transported in melanoma-derived exosomes
      function as intercellular messengers supporting tumor survival and progression.
      Hypoxia increases melanoma phenotypic plasticity, drug resistance, and
      metastasis. MATERIALS AND METHODS: We determined the miRNA profiles in exosomes
      derived from melanoma cells grown under hypoxic and normoxic conditions by
      microarray analyses and reverse transcription-polymerase chain reaction (RT-PCR)
      in order to analyze the potential influence of vesicle-transported miRNAs on
      cancer-related pathways and transcriptional programs. RESULTS: Despite
      phenotypical differences of the four cell lines used, their exosomes shared the
      majority of miRNAs. The levels of three miRNAs were higher in normoxic exosomes,
      whereas 15 miRNAs were significantly more abundant under hypoxic conditions.
      Pathway analysis pointed at several cellular processes contributing to
      proliferation, drug resistance, and modification of the tumor microenvironment,
      including immunosuppression. CONCLUSION: The miRNA-expression profiles of
      exosomes from patient-derived melanoma cells are modified by oxygen concentration
      and reflect the phenotypic changes of melanoma cells under different growth
      conditions.

PMID- 29187457
TI  - Transdermal Delivery of Luteinizing Hormone-releasing Hormone with Chitosan
      Microneedles: A Promising Tool for Androgen Deprivation Therapy.
AB  - Long-term administration of luteinizing hormone-releasing hormone analogs (LHRHa)
      is the main type of androgen-deprivation therapy (ADT) for lethal prostate
      cancer. A fully insertable microneedle system, composed of embeddable chitosan
      microneedles and a dissolvable polyvinyl alcohol/polyvinyl pyrrolidone supporting
      array, was developed for sustained delivery of LHRHa to the skin. A porcine
      cadaver skin test showed that chitosan microneedles can be fully embedded within
      the skin and microneedle-created micropores reseal within 7 days. The measured
      LHRHa loading amount was 73.3+/-2.8 MUg per microneedle patch. After applying
      goserelin-containing microneedles to mice, serum LH levels increased initially
      and then declined below baseline at day 7. In contrast, serum testosterone levels
      increased to reach a peak at day 14 and then declined to a castration level at
      day 21. Additionally, such a castration level was maintained for 2 weeks.
      Therefore, transdermal delivery of goserelin with embeddable chitosan
      microneedles can produce a castrated state in mice. Such a system is a promising,
      feasible means of delivering ADT.

PMID- 29187459
TI  - Cadherin 5 Is a Significant Risk Factor for Hematogenous Recurrence and a
      Prognostic Factor in Locally Advanced Gastric Cancer.
AB  - BACKGROUND/AIM: Cadherin 5 (CDH5) is important for adhesion in epithelial cells,
      and expressed in tumor cells in several malignancies. In the present study, we
      evaluated the clinical significance of CDH5 protein expression in locally
      advanced gastric cancer. MATERIALS AND METHODS: Tumor tissues obtained from 113
      patients with advanced gastric adenocarcinoma who underwent gastrectomy were
      analyzed. RESULTS: High CDH5 expression was significantly associated with
      recurrence (p=0.017), especially hematological recurrence (p=0.022). High CDH5
      expression was a significant risk factor for hematogenous recurrence on
      multivariate analysis (odds ratio[OR]=3.9, confidential interval [CI] 1.0-15,
      p=0.043). Patients with high CDH5 expression had a significantly shorter
      progression-free interval (RFI, p=0.010) than patients with low CDH5 expression.
      High CDH5 expression was an independent prognostic factor on multivariate
      analysis of RFI (hazard ratio[HR]=2.2, 95% CI 1.1-4.3, p=0.021). CONCLUSION: CDH5
      may play a key role in hematogenous recurrence of advanced gastric cancer and may
      be a viable treatment target.

PMID- 29187458
TI  - Radiation Enhances the Efficacy of Antitumor Immunotherapy with an Immunocomplex
      of Interleukin-2 and Its Monoclonal Antibody.
AB  - AIM: An immunocomplex of interleukin-2 (IL-2) and its monoclonal antibody, S4B6
      (IL-2/S4B6), contributes to antitumor immune systems. We investigated the
      antitumor efficacy of radiation (IR) combined with IL-2/S4B6 for osteosarcoma.
      MATERIALS AND METHODS: LM8 mouse osteosarcoma cells were inoculated into both
      legs of C3H mice. For groups treated with IL-2/S4B6 alone, and those treated with
      IR combined with IL-2/S4B6 (COMB), IL-2/S4B6 was intraperitoneally administered
      on days 12 and 16 after tumor cell inoculation. For groups treated with IR alone
      or COMB, one side leg was irradiated at 10 Gy on day 12. RESULTS: Although
      monotherapy with IL-2/S4B6 provided no significant tumor growth inhibition,
      combined therapy significantly reduced tumor volume in both irradiated and
      unirradiated tumors by 99% and 58%, respectively, compared to the no-treatment
      group, with significant induction of CD8+ T-cells in unirradiated tumors.
      Moreover, the combination therapy significantly prolonged overall survival.
      CONCLUSION: Radiation combined with IL-2/S4B6 may be a potential therapeutic
      option for therapy of osteosarcoma.

PMID- 29187461
TI  - Complete Lymph Node Dissection in Melanoma: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: The aim of this meta-analysis was to estimate the survival after
      immediate complete lymph node dissection (CLND) compared to observation only (OO)
      or delayed CLND in patients with melanoma and lymph node metastasis. MATERIALS
      AND METHODS: A systematic search was performed in: PubMed, Web of Science,
      Cochrane Library, CINAHL, Clinical trials and Embase. Eligible studies were
      randomized controlled trials (RCTs) comparing: CLND with OO, or immediate CLND
      with delayed CLND. RESULTS: Four RCTs were included. There was no difference in
      melanoma-specific survival (MSS) (HR=0.91, 95% CI=0.77-1.08, p=0.29). In a
      sensitivity analysis, MSS was higher after immediate CLND compared to delayed
      CLND in patients with nodal metastasis (HR=0.63, 95% CI=0.35-0.74, p=0.0004)
      without evidence of heterogeneity. CONCLUSION: CLND appears to have no additional
      survival benefit after SNB compared to OO. However, subgroup analysis suggests a
      time-dependent benefit for early surgical lymph node removal compared to delayed
      or none.

PMID- 29187460
TI  - Adjuvant Breast Cancer Treatments Induce Changes in Homoarginine Level - A
      Prospective Observational Study.
AB  - AIM: To identify patients with breast cancer at risk for cardiotoxicity, we
      evaluated homoarginine (HA) behavior during adjuvant treatment. PATIENTS AND
      METHODS: Eighty-one patients received radiotherapy (RT) with or without endocrine
      treatment, and 19 received chemotherapy, RT and endocrine therapy. Serum HA,
      asymmetric dimethylarginine (ADMA) and high-sensitivity cardiac troponin T
      (hscTnT) were measured and echocardiography was performed before chemotherapy,
      and before and after RT. RESULTS: In chemo-naive tamoxifen users HA increased
      during RT from a median (IQR) of 2.47 (1.61-3.35) to 2.86 (1.93-4.23) MUM
      (p=0.028) and remained stable in patients with aromatase inhibitor and in those
      without endocrine therapy. Tamoxifen users were mostly spared from
      echocardiographic changes. In chemotherapy-treated patients, HA decreased during
      chemotherapy (p=0.001) from 1.46 (1.01-2.18) to 0.91 (0.71-1.29) MUM, and
      increased (p=0.004) to 1.19 (0.83-1.63) MUM during RT, remaining lower than at
      baseline (p=0.014). Echocardiographic changes were observed during chemotherapy.
      CONCLUSION: HA decrease during chemotherapy could indicate an increased risk of
      cardiovascular morbidity. Additionally, HA increase in tamoxifen users may
      reflect a cardioprotective effect of tamoxifen.

PMID- 29187463
TI  - Multi-Database Description of Primary Splenic Diffuse Large B-Cell Lymphoma.
AB  - BACKGROUND/AIM: Stage I splenic diffuse large B-cell lymphoma (DLBCL) is rare and
      there are few data to guide management. We sought to further define prognosis and
      outcomes. MATERIALS AND METHODS: We utilized the Surveillance, Epidemiology, and
      End Results registry to identify patients with stage I splenic DLBCL diagnosed
      1973-2013. Patients were divided into two cohorts based on the year of diagnosis
      (1983-2005; 2006-2013) as rituximab was approved by the U.S. Food and Drug
      Administration in 2006 for first-line treatment of DLBCL. RESULTS: Utilization of
      splenectomy decreased after the approval of rituximab (82% pre- versus 72%
      rituximab-era). Disease-specific and overall survival were greater with
      splenectomy [hazard ratio (HR)=0.57, p=0.04; and HR=0.66, p=0.03, respectively],
      but this benefit was only seen in the pre-rituximab cohort, not in the rituximab
      era cohort. There was a trend toward improved overall survival with the
      introduction of rituximab (HR=0.75, p=0.054). CONCLUSION: Utilization of
      splenectomy for stage I splenic DLBCL has decreased with the introduction of
      rituximab without compromising outcomes.

PMID- 29187462
TI  - Control of Nausea Based on Risk Analysis in Patients with Esophageal and Gastric
      Cancer Who Received Cisplatin-based Chemotherapy.
AB  - BACKGROUND: Cisplatin is commonly used for esophageal and gastric cancer, but has
      a high emetic risk. Although the control of vomiting is favorable, nausea is
      still poorly controlled in patients receiving cisplatin-based regimens. The
      present study was designed to determine the risks for cisplatin-induced nausea.
      The effect of olanzapine, an antipsychotic drug, as an antiemetic for patients
      with risk of poor control of nausea was subsequently examined. PATIENTS AND
      METHODS: The prevalence of antiemetic medication and the control of nausea and
      vomiting were retrospectively examined in patients with esophageal or gastric
      cancer receiving the first cycle of cisplatin-based chemotherapy. Risks for
      nausea were analyzed by multivariate logistic regression analysis, in which
      threshold for age and cisplatin dose wer assessed by receiver operating
      characteristic curve analysis. RESULTS: A total of 186 patients received
      cisplatin-based regimens during January 2011 and December 2016. Guideline
      consistent antiemetic medication was administered to all patients. Although the
      rate of no vomiting was high (93%), the rate of non-significant (grade 2 or more)
      nausea was insufficient (64%) during the overall period. Risk analysis showed
      that cisplatin dose of 50 mg/m2 or more and female gender were significant risks
      for nausea. Addition of olanzapine, but not of prochlorperazine, to the standard
      antiemetic medication was effective in suppressing nausea in patients who
      experienced nausea in the first cycle. CONCLUSION: Being female and cisplatin
      doses at 50 mg/m2 or more were demonstrated to increase risk for nausea. Addition
      of olanzapine to the standard medication was effective in preventing nausea in
      high-risk patients with esophageal and gastric cancer.

PMID- 29187465
TI  - Esophagogastric Junction Carcinomas - Discriminating Histological Types Through
      Immunohistochemistry.
AB  - BACKGROUND/AIM: Although differentiating squamous cell carcinoma (SCC) from
      adenocarcinoma (AC) at the esophagogastric junction (EGJ) is important for the
      choice of treatment, this can occasionally be difficult with small biopsy
      specimens. Therefore, the purpose of this study was to determine the most useful
      immunomarker panel for discriminating between SCC and AC of the EGJ. MATERIALS
      AND METHODS: We analyzed 15 SCCs and 26 ACs of the EGJ obtained surgically using
      immunohistochemistry. RESULTS: The sensitivities of p40, p63 and cytokeratin 5/6
      were 100% with specificities of 88%, 46% and 81%, respectively, for SCC. The
      sensitivities of CAM5.2, caudal-type homeobox 2 (CDX2), mucin-5AC (MUC-5AC) and
      MUC-6 were 100%, 81%, 77% and 85% with specificities of 27%, 100%, 87% and 87%
      for AC. CONCLUSION: We demonstrated that a two-marker panel of p40 and CDX2 is
      highly sensitive and specific.

PMID- 29187464
TI  - Androgen Receptor in Stage I-II Primary Breast Cancer -Prognostic Value and
      Distribution in Subgroups.
AB  - BACKGROUND/AIM: The value of androgen receptor (AR) in breast cancer has gained
      renewed interest as a prognostic and treatment predictive biomarker. The aims of
      this work were to study the associations and the prognostic value of AR in
      patients from two clinical cohorts. MATERIALS AND METHODS: Cohort 1 included 208
      premenopausal, node-negative patients of whom 87% had received no adjuvant
      medical treatment; cohort 2 consisted of 263 patients with stage II disease who
      had all received 2 years of adjuvant tamoxifen. A semi-quantitative assessment of
      nuclear AR expression divided into five groups (0-1%, 2-10%, 11-50%, 51-75%, and
      76-100%) was performed. Survival analyses, stratified by cohort, were performed
      using both a trend-test and a cut-off of >10% for positivity. RESULTS: A total of
      76% of all patients were AR+, and 89%, 48%, and 23% of the estrogen receptor
      positive, negative, and triple-negative, respectively. In Cox regression,
      stratified by cohort, AR divided into five groups was a prognostic factor for 5
      year distant disease-free survival with a hazard ratio of 0.86 per step in
      fraction score (p=0.018). With a predefined cut-off at 10%, moderate evidence of
      an effect remained (Hazard Ratio=0.67, p=0.077). In multivariable analysis, AR
      did not retain an independent prognostic value. CONCLUSION: AR is a weak,
      however, not independent prognostic factor for distant metastasis. Although the
      prognostic value of AR may be questionable, the study identified a subset of AR
      positive triple-negative patients as being potential candidates for AR-directed
      therapy for which further studies are warranted.

PMID- 29187466
TI  - A Comparison of the Performance of EndoPredict Clinical and NHS PREDICT in 120
      Patients Treated for ER-positive Breast Cancer.
AB  - BACKGROUND: Computational algorithms, such as NHS PREDICT, have been developed
      using cancer registry data to guide decisions regarding adjuvant chemotherapy.
      They are limited by biases of the underlying data. Recent breakthroughs in
      molecular biology have aided the development of genomic assays which provide
      superior clinical information. In this study, we compared the performance in risk
      stratification of EndoPredict Clinical (EPClin, a composite of clinical data and
      EndoPredict) and PREDICT in a cohort of patients with breast cancer considered
      potential candidates for chemotherapy by the clinicians. MATERIALS AND METHODS:
      One hundred and twenty patients with biopsy-proven oestrogen receptor positive
      (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer who
      underwent surgery were included. EPClin and PREDICT were determined for every
      tumour, and the results were compared. RESULTS: Using EPClin scores performed on
      120 tumours, the cohort was stratified into low- (n=60) and high-risk (n=60)
      groups leading to 50% reduction in total chemotherapy prescriptions. PREDICT
      differentiated the patients into low- (n=45), intermediate- (n=33), and high-risk
      groups (n=42). Discordance between scores was demonstrated for 50 (41.66%)
      tumours. Nine (20%) out of 45 patients with low PREDICT scores had high EPClin
      scores and would otherwise not have received chemotherapy if the NHS PREDICT tool
      had been used alone. Eight (19%) out of 42 patients at high risk by PREDICT were
      reclassified as being at low risk by EPClin and avoided adjuvant chemotherapy.
      The sensitivity, specificity, positive predictive value and negative predictive
      value for NHS PREDICT to predict the potential need for chemotherapy as
      determined by EPClin were 85%, 51%, 68% and 80%, respectively. CONCLUSION: To our
      knowledge, this is the first clinical study to compare EPClin and PREDICT. The
      data indicate that computational algorithms such as NHS PREDICT may not
      accurately predict the need for chemotherapy leading to overtreatment,
      undertreatment or uncertainty and anxiety in a significant proportion of
      patients. This underscores the importance of more personalized prognostic tools.

PMID- 29187467
TI  - Diagnostic Performance of Multiparametric Magnetic Resonance Imaging and Fusion
      Targeted Biopsy to Detect Significant Prostate Cancer.
AB  - BACKGROUND/AIM: Multiparametric magnetic resonance imaging combined with
      ultrasound-fusion-targeted biopsy of the prostate intends to increase diagnostic
      precision, which has to be clarified. PATIENTS AND METHODS: We performed
      multiparametric magnetic resonance imaging followed by ultrasound-fusion-guided
      perineal biopsy in 99 male patients with elevated prostate-specific-antigen and
      previous negative standard biopsy-procedures. RESULTS: In 33/99 patients (33%) no
      malignancy could be confirmed by histopathology. Low-grade carcinomas (Gleason
      Score 6+7a) were found in 42/66 (64%) and high-grade carcinomas (Gleason-Score
      >=7b) in 24/66 (36%) men. A high-grade carcinoma corresponded to PI-RADS 4 or 5
      (suspected malignancy) in 21/24 cases, which accounted for a sensitivity of 88%
      and negative-predictive-value of 85% (p=0.002). Differentiation between high-/low
      grade carcinomas (Gleason-Score <=7a vs. >=7b) by means of PI-RADS related to a
      sensitivity of 88% and a negative-predictive-value of 70% (p=0.74). CONCLUSION:
      The results support the view that multiparametric magnetic resonance
      imaging/ultrasound-fusion-guided biopsy promotes considerably higher detection
      rates of clinically relevant prostate malignancies than do conventional
      diagnostic procedures. With regard to differentiation between high- and low-grade
      carcinomas, no significant difference was demonstrated.

PMID- 29187468
TI  - Modeling CA-125 During Neoadjuvant Chemotherapy for Predicting Optimal
      Cytoreduction and Relapse Risk in Ovarian Cancer.
AB  - AIM: To investigate the prognostic value of modeled CA-125 kinetic parameters
      regarding surgery outcomes and time to second-line chemotherapy in a population
      of ovarian cancer patients treated with neoadjuvant chemotherapy followed by
      interval cytoreduction. PATIENTS AND METHODS: This retrospective study included
      consecutive patients with FIGO stage IIIc/IV ovarian cancer treated between 2006
      and 2014. We characterized CA-125 kinetics and identified modeled kinetic
      parameters. RESULTS: Fifty four patients were included. KELIM (modeled CA-125
      elimination rate constant) was an independent predictive parameter of optimal
      cytoreduction (OR=0.18; 95% CI=0.04-0.69; p=0.02). In the optimal cytoreduction
      population (40 patients, 74.1%), E50 (concentration producing 50% of the maximum
      chemotherapy effect) was a significant prognostic parameter regarding time to
      second-line chemotherapy (HR=0.38; 95% CI=0.173-0.854; p=0.019). CONCLUSION: We
      identified CA-125 modeled kinetic parameters during neoadjuvant chemotherapy
      harboring potential predictive values regarding the likelihood of optimal
      cytoreduction, along with time to second-line chemotherapy in optimally
      cytoreduced patients.

PMID- 29187469
TI  - Brachytherapy for Buccal Cancer: From Conventional Low Dose Rate (LDR) or Mold
      Technique to High Dose Rate Interstitial Brachytherapy (HDR-ISBT).
AB  - BACKGROUND/AIM: To examine the effectiveness of newly-installed high-dose-rate
      interstitial brachytherapy (HDR-ISBT) for buccal cancer. PATIENTS AND METHODS: We
      retrospectively reviewed 36 patients (25 men and 11 women) with buccal cancer
      treated with curative brachytherapy with or without external radiotherapy with a
      median follow-up of 99 months. A total of 15 HDR-ISBT (median 48 Gy/ 8 fractions,
      range=24-60 Gy) patients were compared to conventional 15 cases LDR-ISBT (70 Gy,
      range=42.8-110 Gy) and 7 molds techniques (15 Gy, range=9-74 Gy). A total of 31
      patients also underwent external radiotherapy (30 Gy, range=24-48 Gy). They
      comprised of 3T1, 23 T2, 8 T3, 3 T4 including 11 node positive cases. RESULTS:
      HDR-ISBT provided 82% of local control rate at 5 years, whereas conventional
      brachytherapy showed 72% [p=0.44; LDR-ISBT (65%), mold therapy (85.7%)]. Patients
      with early lesions (T1-2 or stage I-II) showed better local control rates than
      those with advanced lesions (T3-4 or stage III-IV). Severe late grade 3
      complications developed in two patients treated with LDR-ISBT and EBRT. There is
      no significant difference in toxicity grade <=2 between conventional
      brachytherapy (5/15=33%) and HDR-ISBT (7/32=32%, p=0.92). CONCLUSION: HDR-ISBT
      achieved good and comparable local control rates to conventional brachytherapy
      without elevating the toxicity.

PMID- 29187470
TI  - The Genomic Alterations of 5alpha-Reductases and Their Inhibitor Finasteride's
      Effect in Bladder Cancer.
AB  - BACKGROUND/AIM: Since androgens affect urothelial bladder cancer (UBC), we
      examined whether 5alpha-reductases (5-AR) have genomic alterations in UBC and
      whether 5alpha-reductase inhibitors (5-ARI) affect UBC. MATERIALS AND METHODS:
      The cBioPortal was used to analyze genomic alternations of 5-ARs in UBC cancer
      genomic datasets. Next, we used the Taiwan National Health Insurance Research
      database to conduct a population-based case-control study to investigate the
      effect of a 5-ARI, finasteride on UBC incidence. We also performed an XTT assay
      to examine the direct effect of finasteride on UBC cells. RESULTS: We found that
      5-AR genomic alternations were observed in 29% of UBC patients and patients with
      alternations had shorter disease-free survival. Also, the use of finasteride with
      >180 cDDDs reduced the risk of UBC. Finasteride could directly inhibit UBC cell
      growth. CONCLUSION: Based on our findings, we concluded that 5-AR could be
      explored as a therapeutic target for UBC with 5-ARIs.

PMID- 29187471
TI  - Resectability and Vascular Management of Retroperitoneal Gynecological
      Malignancies: A Large Single-institution Case-Series.
AB  - BACKGROUND/AIM: To report on morbidity and oncological outcomes in a consecutive
      series of gynecological malignancies involving the vascular district. PATIENTS
      AND METHODS: We retrospectively evaluated a consecutive series between 1/2015 and
      1/2017 with suspicious gynecological malignancies involving the vascular
      district. Peri-operative data and survival rates were computed. RESULTS: Eight
      hundred-four women with gynecological malignancies were admitted for major
      oncologic surgery during the study period, and among them, 50 cases (6.2%) showed
      vascular involvement. Twenty-seven and 23 patients were submitted to minor and
      major vascular procedures, respectively. R0 resection was achieved in 44
      patients. There were no perioperative mortalities. Major postoperative
      complications occurred in 6 patients (12.0%). The 2-year disease free survival
      (DFS) was 67% if R0 resection was achieved. In patients with positive
      pathological margins (n=2), the 2-year DFS was 33%. CONCLUSION: Vascular
      procedures can be safely performed with a proper pre-operative planning and may
      not be an impediment to major gynecological oncological surgery.

PMID- 29187472
TI  - Pilomatrixoma of the Neck/Shoulder Region Mimicking a Rapidly Growing Neoplasm of
      Peripheral Nerve Sheath Origin in Neurofibromatosis Type 1.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disorder.
      Neurofibroma is the most common neoplasm of this disease. This lesion is
      characterized by circumscribed soft or knotty skin tumors derived from peripheral
      nerve sheath cells. Numerous other neoplasms have been described for this tumor
      predisposition syndrome. This case report adds the diagnostic and therapeutic
      procedures in the case of an NF1 patient in whom the rapidly growing, nodular,
      subcutaneous tumor initially led to the suspicion of a malignant neoplasm. The
      tumor proved to be pilomatrixoma, which closely adhered to a neurofibroma.

PMID- 29187473
TI  - Melanoma of the Vagina: Case Report and Systematic Review of the Literature.
AB  - BACKGROUND: Primary melanoma of the vagina (PMV) is a rare entity. The prognosis
      of women with PMV is poor and there is no standardized therapy for this type of
      malignancy. We present the case of a 72-year-old woman with PMV (cT2, pN0, M0).
      CASE REPORT: Imaging studies showed no evidence of regional or distant
      metastases. Molecular analysis demonstrated wild-type B-Raf proto-oncogene,
      serine/threonine kinase (BRAF). Staging laparoscopy with pelvic lymphadenectomy
      and subsequent radiotherapy with 60 Gy delivered as pelvic teletherapy and
      vaginal brachytherapy was applied. Systematic literature review: A total of 805
      cases of PMV were identified. Most lesions were melanotic (65%) and localized
      (66%), whereas amelanotic (35%) and primary advanced lesions (34%) were only seen
      in a minority of patients. BRAF mutation was detected in none out of 33 cases,
      tumor protein 53 (TP53) mutations and mast/stem cell growth factor receptor CD117
      (KIT) amplification were identified in one case each. The most common treatment
      was surgery, reported in 43% of cases. Surgery combined with adjuvant
      radiotherapy, adjuvant immunotherapy (mostly with interferon-alpha), or adjuvant
      chemotherapy were given in 35%, 8%, and 3% of cases, respectively. Radiotherapy
      or chemotherapy as sole treatments were used in 5% and 1% of patients,
      respectively. Among patients with recurrence, chemotherapy (mostly dacarbazine)
      alone or in combination with surgery, radiotherapy or immunotherapy was the most
      common treatment in 61% of cases. The mean durations of recurrence-free and
      overall survival were 16.4 and 22.2 months, respectively. CONCLUSION: PMV is a
      rare malignancy with a poor prognosis. Surgery, radiotherapy, and immunotherapy
      with interferon-alpha are the mainstay of treatment for localized disease, while
      chemotherapy with dacarbazine is mostly used for unresectable and recurrent
      disease. No data on the clinical value of immune checkpoint inhibitors in PMV
      have been published.

PMID- 29187474
TI  - Plasma Glutathione Peroxidase (GPX1) Levels and Oxidative Stress in Gallstone
      Patients Operated with Two Different Cholecystectomy Techniques: A Randomized
      Study with Special Reference to Cancer Patients.
AB  - BACKGROUND/AIM: The plasma glutathione peroxidase (GPX1) levels in gallstone
      patients operated with laparoscopic cholecystectomy (LC) or minicholecystectomy
      (MC) versus cancer patients is unknown. PATIENTS AND METHODS: Initially, 114
      patients with symptomatic gallstone disease were randomized into LC (n=53) or MC
      (n=61) groups. Plasma levels of C-reactive protein (hs-CRP) and the oxidative
      stress marker GPX1 were measured at three time points; before (PRE), immediately
      after (POP1) and 6 hours after operation (POP2). The end-point of our study was
      to determine a correlation between the plasma hs-CRP and GPX1 levels in the LC
      and MC patients versus cancer patients. RESULTS: The plasma GPX1 levels
      preoperatively and following surgery in the LC and MC patients versus cancer
      patients were quite similar (p=0.509, p=0.578, p=0.882, respectively). The
      patients with inflammation of the gallbladder wall (IGW) versus no-IGW had
      significantly higher plasma GPX median (interquartile range) levels
      preoperatively (11.5; 6.2-17.4 vs. 8.0; 5.6-14.5, p=0.033) and the GPX values
      following surgery (POP1, 11.4; 7.8-14.7 versus 7.3; 4.4-11.0, p=0.019 and POP2,
      11.5; 7.1-16.2 versus 9.4; 4.2-13.1, p=0.027). The IGW in patients with LC and MC
      groups combined, correlated significantly to the plasma CRP levels preoperatively
      (r=0.280, p=0.005) and the CRP values following surgery (POP1, r=0.295, p=0.003
      and POP2, r=0.338, p=0.001) and the GPX1 values postoperatively (POP1, r=0.319,
      p=0.001 and POP2, r=0.243, p=0.026) and to the length of the skin incision
      (r=0.248, p=0.009). CONCLUSION: The plasma GPX1 levels preoperatively and
      following surgery in the LC and MC patients versus cancer patients were quite
      similar. However, the inflammation of the gallbladder wall (IGW) correlated
      significantly with plasma GPX1 and hs-CRP values suggesting that inflammation and
      oxidative stress are related.

PMID- 29187475
TI  - Reliable Radiation Technique to Minimize Ovarian Dose During Radiation
      Prophylaxis of Heterotopic Ossification.
AB  - BACKGROUND/AIM: Scattered radiation during radiotherapy (RT) directed at the hip
      joint poses concerns about ovarian function in patients of reproductive age.
      Here, we report the impact of using a split-beam technique (SBT) and different
      photon energies on the total ovary dose during radiation prophylaxis of
      heterotopic ossification (HO). PATIENTS AND METHODS: This was a single
      institution, retrospective study of 32-patients with traumatic acetabular
      fractures (TAF). All underwent surgery followed by CT-based-RT within 72 h in a
      single fraction of 700 cGy. Ipsilateral (IL) and contralateral (CL) ovaries (OV)
      were contoured separately and dose volume histograms (DVH) generated. Additional
      planning trials were created for each patient by utilizing a SBT medially and by
      using different photon energies (6-18 MV) to investigate the difference in ovary
      dose among these maneuvers. RESULTS: The median Mean-dose delivered to ILOV was
      59 cGy and the median Max-dose was 177 cGy. CLOV median Mean-dose was 6 cGy and
      median Max-dose was 10 cGy. SBT at the medial edge of the field led to a 27% and
      22% dose reduction in the median Mean and Max. doses, respectively, to ILOV; 9%
      and 5% reduction was seen in the median Mean and Max. doses, respectively, to
      CLOV. Higher photon energies (10-18 MV) led to an additional 28% and 16 %
      reduction in median Mean and Max. doses, respectively, to ILOV when compared to
      those from 6 MV. The CLOV median Mean dose was reduced by 18% and the Max. dose
      was reduced by 12%. CONCLUSION: A biologically significant radiation dose is
      delivered to the ovaries during HO radiation prophylaxis at the hip joints.
      Ipsilateral ovarian dose could be reduced by half and contralateral by one
      quarter by using CT-based treatment planning with a medial SBT and photon
      energies above 6 MV. We suggest using no more than 10 MV to minimize neutron
      contamination. Those techniques should be the standard of care as it provides a
      reliable method for minimizing the radiation dose to the ovaries, consequently,
      maximizing female fertility preservation during HO radiation prophylaxis. All
      female patients in childbearing age should be fully informed about ovarian
      radiation exposure and possible temporary alteration in ova production and
      morphology.

PMID- 29187476
TI  - A Case of the Resected Lymphohistiocytoid Mesothelioma: BAP1 Is a Key of Accurate
      Diagnosis.
AB  - BACKGROUND: Malignant mesothelioma (MM) is a well-known malignant tumor that
      occurs in the pleura and is histopathologically classified into three subtypes.
      Lymphohistiocytoid mesothelioma (LHM) is considered a variant of epithelioid MM,
      and few cases have been reported. First case of LHM was reported by Henderson et
      al. in 1988. It is difficult to precisely diagnose LHM, and it is often
      misdiagnosed as reactive mesothelial cell proliferation. CASE REPORT: An 82-year
      old man, with the smoking history of nine pack-years, was referred to our
      Department due to an abnormal shadow and pleural effusion in the left lung field
      on the chest X-ray imaging. His occupation was a teacher through his life without
      any asbestos exposure. Computed tomography (CT) and 18F-fluorodeoxyglucose
      position emission tomography showed a tumor which was suggestive of malignancy on
      the left chest wall, with the possible invasion into the left 2nd to 4th ribs. He
      underwent a CT-guided biopsy and a thoracentesis, but the tumor was shown to be a
      benign tumor indicative of a reactive mesothelial cell proliferation. Then, he
      underwent a surgical resection and the tumor was suspected of liposarcoma
      macroscopically. Histological and immunohistochemical findings were suggestive of
      mesothelial lesion, such as nodular histiocytic or mesothelial hyperplasia.
      However, loss of BAP1 and no p16 homozygous deletion in the tumor cells led to
      the diagnosis of LHM, not a benign lesion.

PMID- 29187477
TI  - Proteins Annexin A2 and PSA in Prostate Cancer Biopsies Do Not Predict
      Biochemical Failure.
AB  - BACKGROUND/AIM: We previously reported the use of mass spectrometry and western
      blotting to identify proteins from tumour regions of formalin-fixed paraffin
      embedded biopsies from 16 men who presented with apparently localized prostate
      cancer, and found that annexin A2 (ANXA2) appeared to be a better predictor of
      subsequent biochemical failure than prostate-specific antigen (PSA). MATERIALS
      AND METHODS: In this follow-up study, ANXA2 and PSA were measured using western
      blotting of proteins extracted from biopsies from 37 men from a subsequent
      prostate cancer trial. RESULTS: No significant differences in ANXA2 and PSA
      levels were observed between men with and without biochemical failure. The
      statistical effect sizes were small, d=0.116 for ANXA2, and 0.266 for PSA.
      CONCLUSION: ANXA2 and PSA proteins measured from biopsy tumour regions are
      unlikely to be good biomarkers for prediction of the clinical outcome of prostate
      cancer presenting with apparently localized disease.

PMID- 29187478
TI  - The Relationship Between Peripheral Neuropathy Induced by Docetaxel and Systemic
      Inflammation-based Parameters in Patients with Breast Cancer.
AB  - BACKGROUND/AIM: Docetaxel often induces peripheral neuropathy (PN). The aim of
      this study was to elucidate the relationship between PN and systemic inflammation
      parameters, namely the neutrophil-to-lymphocyte ratio (NLR), platelet-to
      lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). PATIENTS AND
      METHODS: We retrospectively evaluated 67 patients with breast cancer who were
      treated with docetaxel. Thirty patients (44.8%) had received previous
      chemotherapy including anthracycline. RESULTS: Overall, 51 patients (76.1%)
      experienced PN. All the parameters increased with the number of administered
      courses of docetaxel. In an analysis of patients without previous chemotherapy,
      those suffering from PN had a significantly higher NLR at the first and third
      cycles than those not suffering from PN (2.9 vs. 2.0, and 3.1 vs. 2.6,
      respectively, both p<0.05), and the MLR at the first cycle was also significantly
      higher in those with PN than in those without (0.18 vs. 0.15, p<0.05).
      CONCLUSION: Systemic inflammation appears to contribute to the occurrence of PN
      induced by docetaxel.

PMID- 29187479
TI  - Predictive Significance of Thymidylate Synthase Expression in Non-small Cell Lung
      Cancer.
AB  - BACKGROUND/AIM: To date, many studies have suggested that thymidylate synthase
      (TS) could be used as a prognostic and predictive marker in non-small cell lung
      cancer (NSCLC) patients. However, results have been contradictory. The aim of
      this study was to evaluate TS mRNA levels in tumor tissue of NSCLC patients who
      underwent complete surgical resection and to analyze its prognostic and
      predictive potential. MATERIALS AND METHODS: The study group consisted of 64
      patients who underwent curative lung resection. Paired lung tissue samples were
      taken directly from the tumor tissue and from adjacent, histologically cancer
      free lung tissue. The quantitative estimation of TS expression was performed by
      reverse transcription real-time polymerase chain reaction (RT-qPCR). The
      relationship between TS expression level and disease-free interval (DFI) and
      overall survival (OS) was analyzed. RESULTS: There was significantly higher TS
      expression in NSCLC tumor tissue comparing to normal lung tissue. In the group of
      patients who received adjuvant chemotherapy based on platinum derivatives in
      combination with paclitaxel or gemcitabine, we found shorter DFI (p=0.0473) and
      OS (p=0.0053) in those with high expression of TS. CONCLUSION: Our results
      demonstrated the relationship of high tumor tissue TS levels to adverse prognosis
      in patients undergoing adjuvant chemotherapy. TS is a non-specific tumor marker
      with respect to NSCLC, therefore we think that its best use would be as a member
      of the panel of predictors of adjuvant treatment efficacy.

PMID- 29187480
TI  - Clinical Efficacy of Carbon Ion Radiotherapy for Unresectable Chondrosarcomas.
AB  - BACKGROUND: Carbon ion radiotherapy has precise dose distribution and high
      biological effectiveness and is likely a promising therapy for patients with
      sarcomas. We evaluated the outcomes of carbon ion radiotherapy in patients with
      unresectable chondrosarcomas. PATIENTS AND METHODS: A retrospective analysis of
      75 tumors in 73 patients treated with carbon ion radiotherapy was performed.
      There were 26 spinal, 38 pelvic, and 11 other types of tumors. Seventy
      conventional and five dedifferentiated chondrosarcomas were treated in 69 and
      four patients, respectively. RESULTS: The median follow-up period was 49.4
      (range=6.4-146.4) months. The 5-year local control, overall survival, and disease
      free survival rates were 53%, 53%, and 34%, respectively. By multivariate
      analysis, tumor volume and histological grade were significantly related to
      overall and disease-free survival. Five patients required surgical intervention
      because of adverse events in the bones. CONCLUSION: Carbon ion radiotherapy might
      be a treatment option for unresectable chondrosarcoma.

PMID- 29187481
TI  - Pre-surgical Multiparametric Assessment of Breast Lesions Using 3-Tesla Magnetic
      Resonance.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate experience with
      multiparametric breast imaging on 3-Tesla magnetic resonance (3T-MRI) scanner
      using a dedicated 18-channel coil compared to histological findings in women
      after surgery. MATERIALS AND METHODS: The study included 100 women with 105
      Breast Imaging Reporting and Data System (BI-RADS) 4 to 6 lesions by mammography
      who were examined using 3T-MRI and subsequently underwent surgery. MRI included
      non-contrast T1, T2 and T2 short tau inversion recovery (STIR) sequences,
      diffusion-weighted imaging with apparent diffusion coeficient maps, postcontrast
      dynamic study and single-voxel MRI spectroscopy. The results were compared to
      those of histopathological examination. RESULTS: A sensitivity of 98.68% was
      found for the whole population, with a specificity of 86.20%. The most valuable
      findings were diffusion restriction with sensitivity of 90.79% and specificity of
      89.66%, and increased choline in the spectrum with sensitivity of 68.42% and
      specificity of 93.10%. Evaluation of the enhancement curve had sensitivity of
      45.05% and specificity of 72.41%. In examination of lymph nodes, 3T-MRI had
      sensitivity of 92.59% and specificity of 93.87%. CONCLUSION: Multiparametric 3T
      MRI breast imaging shows excellent results in evaluation of breast cancer
      compared to histological findings, both for primary tumor and nodal metastases.
      The greatest contribution to improving diagnostic performance is the evaluation
      of diffusion.

PMID- 29187482
TI  - Predictors of Cure of Intrahepatic Cholangiocarcinoma After Hepatic Resection.
AB  - BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is the second most common
      primary liver cancer after hepatocellular carcinoma, and has a poor prognosis.
      Surgical resection is the only option for a cure of ICC. Here we attempted to
      define the cure rate after hepatic resection for ICC and to identify the
      predictors for a cure. PATIENTS AND METHODS: Among the 96 patients who underwent
      R0 resections for primary ICC between 1990 and 2011 at the Kumamoto University
      Hospital and Kyushu University Hospital, those who were followed for >=5 years
      after surgery were enrolled. "Cure" was defined as recurrence-free survival (RFS)
      of >=5 years after surgery. RESULTS: A total of 81 patients were eligible. A cure
      was achieved in 37 patients (45.7%). The 5-year overall survival and RFS rates
      were 55.0% and 41.7%, respectively. A multivariate logistic regression analysis
      identified the absence of lymph node metastasis (relative risk (RR) 7.5, p=0.011)
      and the absence of microvascular invasion (RR 5.5, p=0.0137) as the independent
      predictors of achieving a cure. CONCLUSION: R0 resections achieved a cure in
      45.7% of this series of ICC patients. The predictors of a cure identified here,
      i.e., absence of lymph node metastasis and absence of microvascular invasion,
      could contribute to the selection of patients who are not candidates for adjuvant
      chemotherapy.

PMID- 29187483
TI  - Palonosetron Prevents Highly Emetogenic Chemotherapy-induced Nausea and Vomiting
      in Oral Cancer Patients.
AB  - BACKGROUND/AIM: To evaluate the efficacy of palonosetron in preventing acute and
      delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy
      (HEC) in oral cancer patients. PATIENTS AND METHODS: Oral cancer patients
      receiving HEC were enrolled; among the 40 patients, 87 courses of chemotherapy
      were administered. On day 1, 0.75 mg palonosetron was intravenously administrated
      just before chemotherapy. RESULTS: The primary endpoint was the proportion of
      patients with a complete response (CR) and the secondary endpoint was the
      proportion of patients with complete control (CC) during the acute and delayed
      phase. During the acute phase, 86 of 87 courses (98.9%) had CR and 84 of 87
      courses (96.6%) had CC. During the delayed phase, 84 of 87 courses (96.6%) had CR
      and 70 of 87 courses (80.5%) had CC. CONCLUSION: Palonosetron is effective at
      preventing HEC-induced chemotherapy-induced nausea and vomiting (CINV) in oral
      cancer chemotherapeutic regimens in the acute and delayed phases.

PMID- 29187484
TI  - Phase II Study of Concurrent Chemoradiotheapy Using Nedaplatin for Locally
      Advanced Uterine Cervical Carcinoma (KGROG0501): Final Results.
AB  - AIM: This phase II study using nedaplatin evaluated the effectiveness and safely
      of concurrent chemoradiotherapy for locally advanced uterine cervical carcinoma.
      PATIENTS AND METHODS: Patients met the following eligibility criteria,:
      International Federation of Gynecology and Obstetrics (FIGO) stage Ib, IIa, IIb
      with bulky tumor (>=40 mm) or pelvic lymph node swelling (>=10 mm), in FIGO stage
      IIIa, IIIb or IVa. Treatment adopted external radiation therapy combined with
      intracavitary brachyhtherapy using weekly nedaplain at 30 mg/m2 totaling five
      cycles. The primary endpoint was 3-year overall survival. RESULTS: From June 2005
      to May 2010, 45 eligible patients with uterine cervical carcinoma were
      registered. Histopathology was squamous cell carcinoma in 36 and adenocarcinoma
      in nine. The median follow-up period was 39 months. The 3-year overall survival
      rate was 73.0% (95% confidence interval=56.2-84.2%). No severe acute or late
      toxicities occurred. CONCLUSION: This phase II study showed external radiation
      therapy combined with intracavitary brachyhtherapy using weekly nedaplain to be
      effective and safe.

PMID- 29187485
TI  - Primary Urinary Tract Lymphoma: Rare but Aggressive.
AB  - BACKGROUND: Primary urinary tract lymphoma (PUTL) is an uncommon disease with
      only a few case reports in the literature. MATERIALS AND METHODS: Information
      about 1,264 patients diagnosed between 1983 and 2013 with PUTL was extracted from
      the Surveillance, Epidemiology and End Results database. Kaplan-Meier curves and
      multivariable regression analysis were used to analyze the survival and identify
      prognostic factors. A comparison of nodal diffuse large B-cell lymphoma (DLBCL)
      with PUTL DLBCL was performed. In addition, we compared the characteristics of
      kidney and bladder lymphoma. RESULTS: PUTL incidence was 1 case/1,000,000 people
      per year. DLBCL was found to be the predominant histology. Five-year overall
      survival and cancer-specific survival were 49% and 58%, respectively. DLBCL
      histology, male gender, stage III-IV disease, and advanced age were found to be
      poor prognostic factors. Surgery may be beneficial. Urinary tract DLBCL has a
      worse prognosis than nodal DLBCL. CONCLUSION: To our knowledge, this is the
      largest population-based study of PUTL in the literature. The survival of
      patients has not improved in the era of modern therapies therefore new treatments
      are needed.

PMID- 29187486
TI  - Relationship Between Preoperative Sarcopenia Status and Immuno-nutritional
      Parameters in Patients with Early-stage Non-small Cell Lung Cancer.
AB  - BACKGROUND: Although the skeletal muscle in the region of the third lumbar
      vertebra (L3) is generally assessed in order to judge sarcopenia, not every
      patient with non-small cell lung cancer (NSCLC) undergoes computed tomography
      including the L3 region. We hypothesized that immuno-nutritional parameters could
      predict the existence of sarcopenia in patients with NSCLC. AIM: The aim of this
      study was to retrospectively investigate the correlation between preoperative
      sarcopenia and immuno-nutritional parameters in patients with early-stage NSCLC.
      PATIENTS AND METHODS: We selected 147 of patients with pathological stage I NSCLC
      who underwent preoperative measurement of immuno-nutritional parameters and CT
      including the L3 region. RESULTS: Preoperative sarcopenia was significantly
      associated with female gender (p=0.0003) and poor prognosis (p=0.0322). In Kaplan
      Meier analysis of overall survival (OS) by preoperative sarcopenia status, the
      sarcopenic group had significantly shorter OS than the non-sarcopenic group (5
      year OS: 87.27% vs. 77.37%, p=0.0131, log-rank test). In multivariate analysis,
      the preoperative sarcopenia status (hazard ratio=5.138; 95% confidence
      interval=2.305-11.676; p<0.0001) was an independent prognostic factor.
      Preoperative sarcopenia status was significantly related to controlling
      nutritional status score (p=0.0071) and Geriatric Nutritional Risk Index (GNRI)
      (p<0.0001). Spearman's correlation test showed good significant correlation
      between preoperative sarcopenia status and GNRI (r=0.348, p<0.0001). CONCLUSION:
      The preoperative GNRI is a simple and useful predictor for existence of
      preoperative sarcopenia which was associated with poor outcome in patients with
      early-stage NSCLC.

PMID- 29187487
TI  - Stereotactic Body Radiation Therapy in Primary and Metastatic Liver Disease.
AB  - BACKGROUND/AIM: The aim of this study was to investigate the treatment outcomes
      and toxicities in patients with liver disease treated by Stereotactic Body
      Radiation Therapy (SBRT). PATIENTS AND METHODS: From 2007 to 2016, 43 patients
      with 58 lesions (6 primary and 37 metastatic liver tumors) were treated with
      SBRT. RESULTS: Local Control was reached in 47 out of 58 (81%) treated lesions
      with 12 and 24-month rates of 81% and 74% respectively. The progression-free
      survival at 12 and 24 months was 42% and 36%, respectively. The disease specific
      survival at 12 and 24 months was 74% and 46% respectively. Median overall
      survival (OS) was 20 months and the rates of OS were 74% and 46% at 12 and 24
      months respectively. Toxicity was very low consisting mainly of Grade 1 and 2.
      CONCLUSION: SBRT provides good local control for both primary and metastatic
      liver lesions, with minimal toxicity.

PMID- 29187488
TI  - Predictive Factors and a Survival Score for Patients Irradiated for Metastatic
      Spinal Cord Compression from Carcinoma of the Salivary Glands.
AB  - AIM: To our knowledge, this is the first study focusing on metastatic spinal cord
      compression (MSCC) from carcinoma of the salivary glands. PATIENTS AND METHODS:
      Nine patients receiving radiation alone were evaluated for improvement of motor
      deficits, post-radiation gait function and survival. RESULTS: Of nine
      characteristics (radiation program, age, sex, additional metastases to bone or to
      other organs, dynamic of motor deficits, pre-radiation gait function, number of
      vertebrae affected by MSCC, general condition), strong trends were found for
      associations between improved motor deficits and their dynamic (p=0.05), post
      radiation gait function and pre-treatment ambulatory status (p=0.08) and between
      survival and additional metastases to other organs (p=0.07), dynamic of motor
      deficits (p=0.07) and general condition (p=0.07). In addition, a survival score
      was created. Patients with 2-3 points had a significantly better 6-month survival
      than those with 0-1 points (100% vs. 0%, p=0.027). CONCLUSION: Characteristics
      predicting outcomes identified in this study and the new survival score can guide
      physicians when making treatment decisions.

PMID- 29187489
TI  - Pancreatic Mucinous Cystic Neoplasm Communicating with Main Pancreatic Duct: An
      Unrecognized Presentation of Pancreatic Mucinous Neoplasm?
AB  - Mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms
      (IPMNs) are two well recognized entities of precursor cystic lesions of
      pancreatic duct adenocarcinoma. The characteristic features of MCNs are the lined
      mucinous epithelium with underlying ovarian-type stroma, but without
      communication with the ducts, while that for IPMNs are the communication with the
      ducts but without the underlying ovarian-type stroma. Here we report a case of
      MCN communicating with the main pancreatic duct in a 68-year-old woman. The
      initial radiographic diagnosis was pancreatic IPMN with main pancreatic
      involvement and this was also confirmed during gross examination. Histologically,
      the pancreatic cystic neoplasm was lined with mucinous epithelium with underlying
      ovarian-type of stroma. Immunohistochemical stains confirmed that the stroma
      cells were positive for ER, PR, alpha-inhibin and focally positive for CD10. The
      final pathologic diagnosis was pancreatic mucinous cystic neoplasm communicating
      with the main pancreatic duct. To the best of our knowledge, this is the second
      pathology confirmed case of MCN communicating with the main pancreatic duct. A
      careful gross examination and bivalvation of the main duct communicating with the
      cystic neoplasm helps render the correct diagnosis. If more cases are reported in
      the future, the MCN communicating with duct could become a new entity of
      pancreatic mucinous neoplasm.

PMID- 29187490
TI  - A Prospective Study of Intensity-modified Radiation Therapy in Comparison with
      Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement.
AB  - BACKGROUND/AIM: Intensity-modulated radiation therapy (IMRT) is a form of
      radiation therapy that allows accurate irradiation with reduced damage to
      surrounding tissues. Here, we analyzed borderline-resectable pancreatic cancer
      (BRPC) with arterial abutment (BR-A) patients with IMRT as neoadjuvant therapy
      and performed comparisons with patients with conventional RT to clarify the
      advantages of IMRT as a neoadjuvant therapy. PATIENTS AND METHODS: Thirty BR-A
      patients treated at our hospital between January 2012 and December 2015 were
      divided into two groups: 12 patients underwent conventional 3D-RT before
      resection (RT group); and 18 patients underwent IMRT before resection (IMRT
      group). We analyzed safety, tumor resection rate, histological classification of
      the tumor and overall survival. RESULTS: The R0 rate was 84% for the IMRT group
      and 83% for the RT group. Local therapeutic effects as assessed by Evans
      classification showed a higher local control rate in the IMRT group (Grade: 1,
      0%; 2a, 25%; 2b, 41.6%; 3, 17%; 4, 8%) than in the RT group (Grade: 1, 17%; 2a,
      50%; 2b, 17%; 3, 17%; 4, 0%). The cumulative dose of S1 treatment as adjuvant
      therapy was much smaller in the RT group (18.3%) compared to that in the IMRT
      group (57.1%, p=0.047), and with better subsequent overall survival rate (MST 32
      months vs. 13.8 months, p=0.0273). CONCLUSION: The IMRT group showed a better
      control rate than the RT group. The neoadjuvant IMRT has advantages of higher
      completion rate of adjuvant chemotherapy with better nutritional status and
      better subsequent overall survival rate (OS).

PMID- 29187492
TI  - FOLFOX as First-line Therapy for Gastric Cancer with Severe Peritoneal
      Metastasis.
AB  - BACKGROUND/AIM: Severe peritoneal metastasis (PM) from advanced gastric cancer
      (AGC) causes massive ascites and inadequate oral intake. Because patients with
      severe PM are often not included in clinical trials, little is known regarding
      the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous
      infusion of 5-fluorouracil (FOLFOX) for them. PATIENTS AND METHODS: We
      retrospectively studied AGC patients with massive ascites and/or inadequate oral
      intake due to severe PM treated with FOLFOX as the first-line treatment. RESULTS:
      Only 39 (10%) of 378 AGC patients had severe PM; 10 received FOLFOX. The median
      progression-free and overall survivals were 7.5 and 13.2 months, respectively.
      Ascites decreased in seven of nine patients with ascites, and oral intake
      improved in four of seven patients with an inadequate oral intake. Common grade 3
      4 adverse events included neutropenia and anemia. CONCLUSION: This study suggests
      that FOLFOX is effective and manageable for AGC patients with severe PM.

PMID- 29187491
TI  - Incidence and Risk Factors of Symptomatic Hiatal Hernia Following Resection for
      Gastric and Esophageal Cancer.
AB  - BACKGROUND/AIM: Symptomatic hiatal hernia (HH) following resection for gastric or
      esophageal cancer is a potentially life-threatening event that may lead to
      emergent surgery. However, the incidence and risk factors of this complication
      remain unclear. PATIENTS AND METHODS: Data of patients who underwent resection
      for gastric or esophageal cancer between 2005 and 2012 were assessed and the
      incidence of symptomatic HH was evaluated. Factors associated with an increased
      risk for HH were investigated. RESULTS: Resection of gastric or esophageal cancer
      was performed in 471 patients. The primary tumor was located in the stomach,
      cardia and esophagus in 36%, 24%, and 40% of patients, respectively. The
      incidence of symptomatic HH was 2.8% (n=13). All patients underwent surgical
      hernia repair, 8 patients (61.5%) required emergent procedure, and 3 patients
      (23%) underwent bowel resection. Morbidity and mortality after HH repair was 38%
      and 8%, respectively. Factors associated with increased risk for symptomatic HH
      included Body-Mass-Index (median BMI with HH 27 (23-35) vs. BMI without HH 25 (15
      51), p=0.043), diabetes (HH rate: with diabetes, 6.3% vs. without diabetes, 2%,
      p=0.034), tumor location (HH rate: stomach, 1.2% vs. esophagus, 1.1% vs. cardia,
      7.9%, p=0.001), and resection type (HH rate: total/subtotal gastrectomy, 0.7% vs.
      transthoracic esophagectomy, 2.7% vs. extended gastrectomy, 6.1%, p=0.038).
      CONCLUSION: HH is a major adverse event after resection for gastric or esophageal
      cancer especially among patients undergoing extended gastrectomy for cardia
      cancer requiring a high rate of repeat surgery. Therefore, intensive follow-up
      examinations for high-risk patients and early diagnosis of asymptomatic patients
      are essential for selecting patients for elective surgery to avoid unpredictable
      emergent events with high morbidity and mortality.

PMID- 29187493
TI  - BRAF, NRAS and C-KIT Advanced Melanoma: Clinico-pathological Features, Targeted
      Therapy Strategies and Survival.
AB  - BACKGROUND/AIM: The mutational status of stage III and IV melanomas should be
      recognized in order to allow for targeted therapies. The aim of our study was the
      characterization of BRAF, NRAS and C-KIT melanoma patients, in order to define
      their optimal management. PATIENTS AND METHODS: Between 1991 and 2015, 63 mutated
      melanoma patients were treated and monitored during their diagnostic and
      therapeutic management at a single institution. RESULTS: BRAF-mutated melanoma
      patients were the most common, representing 70% of the study population, while
      NRAS- and C-KIT-mutated melanoma represented 19% and 11% respectively. BRAF
      mutated melanomas were mostly located at sites of intermittent sun exposure, and
      were associated with higher Breslow thickness and an increased number of mitosis.
      NRAS mutated melanoma were mainly observed in chronic sun-damaged areas and had a
      negative prognostic value, with shorter time to progression and a high incidence
      of central nervous system involvement. C-KIT mutated melanoma were located at
      acral and mucosal sites. Overall survival observed in the three groups of
      patients revealed wide differences. CONCLUSION: BRAF, NRAS and C-KIT melanomas
      constitute distinct clinico-pathological entities. BRAF-mutated melanoma benefit
      from both anti-BRAF and anti-MEK targeted therapies while triple-negative
      melanomas could benefit from novel anti-CTLA-4 and anti-PD-L1 immunotherapeutic
      approaches.

PMID- 29187494
TI  - Characterization of Prognostic Factors and the Efficacy of Adjuvant S-1
      Chemotherapy in Patients with Post-surgery Extrahepatic Bile Duct Cancer.
AB  - BACKGROUND/AIM: There is no clear consensus on the type of adjuvant therapy that
      should be used for patients with extrahepatic bile duct cancer. PATIENTS AND
      METHODS: Two hundred and seventy-one patients that had undergone surgical
      resection for extrahepatic bile duct cancer composed the study cohort.
      Demographics, treatments, and relationships between the potential prognostic
      factors and survival rates were analyzed. RESULTS: The overall 3-year and 5-year
      survival rates for post-surgery extrahepatic bile duct cancer patients were 49.0%
      and 35.4%, respectively. Multivariate analysis revealed that regional lymph node
      metastasis was an independent negative prognostic factor. We observed a
      significant correlation between node-positive extrahepatic bile duct cancer and
      postoperative local recurrence, liver metastasis, peritoneal dissemination, and
      post-surgery lymph node metastasis. Adjuvant S-1 chemotherapy showed a favorable
      hazard ratio in patients with lymph node metastases or positive vascular
      invasion. CONCLUSION: We recommend the use of adjuvant S-1 therapy in patients
      with lymph node metastases or microvascular invasion.

PMID- 29187495
TI  - Outcome Evaluation of HER2 Breast Cancer Patients with Limited Brain Metastasis.
AB  - BACKGROUND/AIM: To appraise the outcome of limited brain metastasis (BMs) from
      HER2 breast cancer. PATIENTS AND METHODS: The study cohort included sixty-six
      patients Treatments consisted of surgery followed by radiotherapy (RT), or
      radiosurgery (SRS/HSRS) or whole brain radiotherapy (WBRT). RESULTS: Surgery
      followed by RT was performed in 25.8% of patients, SRS/HSRS alone in 48.5%, and
      WBRT alone in 25.7%. The median follow-up time was 23.4 months and 32.5 months
      for alive patients. Local recurrence occurred in 16 (24.2%) patients. The median,
      1-, 2-, 3-year local control were (median not reached=nr), 87.5%, 71.2%, and
      63.0%. The median 1-, 2-, 3-year overall survival were 30.7 months (95%CI: 18.9
      42.6 months), 78.5%, 57.4%, 43.3%. Karnofsky Performance Scale (KPS), number of
      BMs, local treatment performed, the presence of extracranial (EC) metastases at
      the time of BMs diagnosis, and the administration of trastuzumab affected
      survival. CONCLUSION: HER2BC patients with good performance status, controlled EC
      disease and single BM had better outcome. In this long-term survivor patients,
      local BMs treatment can affect survival.

PMID- 29187496
TI  - Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently
      Involve KRAS Mutations and Malignant Progression.
AB  - BACKGROUND: Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a
      malignant potential, but indolent MCNs are not uncommon. MATERIALS AND METHODS:
      The pathological and genetic characteristics of resected MCNs (n=15) categorized
      by the amount of mucin of the lining epithelium were investigated. RESULTS: MCNs
      were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than
      half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor
      (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in
      the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all
      patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat
      sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%)
      (p-MCN; 11%, p<0.05). CONCLUSION: Mucinous MCNs more frequently have KRAS
      mutations and higher risk of malignant progression.

PMID- 29187497
TI  - A Glissonean Approach with Individual Isolation During Right Hemi-Hepatectomy
      After Portal Vein Embolization.
AB  - BACKGROUND/AIM: Although the Glissonean approach in hemi-hepatectomy is a very
      useful technique, right hemi-hepatectomy with Glissonean approach after portal
      vein embolization (PVE) is difficult because of the obstructing materials located
      at the right portal branch. The aim of this study was to evaluate the utility of
      the Glissonean approach with an individual isolation technique (GI technique) in
      right hemi-hepatectomies after PVE. PATIENTS AND METHODS: We retrospectively
      analyzed 21 patients who underwent the GI technique between March 2007 and June
      2012. RESULTS: In one of the 21 patients, we could not perform the GI technique
      because of severe adhesions following previous operation; however, there were no
      troubles in the remaining 20 cases. In addition, none of the patients that were
      treated using this method developed massive ascites after right hemi-hepatectomy,
      despite 8 patients (40%) exhibiting severe fibrosis (F3 or F4). CONCLUSION: Even
      in right hemi-hepatectomy following PVE, our GI technique may be a useful
      procedures for patients.

PMID- 29187498
TI  - Association Between PD-L1 Expression and Metabolic Activity on 18F-FDG PET/CT in
      Patients with Small-sized Lung Cancer.
AB  - AIM: We evaluated the metabolic characteristics of small-sized lung cancer using
      18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG
      PET/CT) with regard to programmed cell death ligand 1 (PD-L1) expression.
      MATERIALS AND METHODS: PD-L1 expression was evaluated by immunohistochemistry
      with the antibody clone SP142 in 263 patients with surgically resected primary
      small-sized lung cancer. Specimens with <5% tumor membrane staining were
      considered negative. We examined the association between the frequency of PD-L1
      expression and the maximum standardized uptake value (SUVmax) in preoperative 18F
      FDG PET/CT. RESULTS: Among patients with non-small cell lung cancer (NSCLC), the
      SUVmax was significantly higher in those with PD-L1 expression than in those
      without (p<0.0001). However, there was no correlation between SUVmax and PD-L1
      expression in patients with neuroendocrine tumors (p=0.9638). Multivariate
      analysis revealed that smoking and a high SUVmax were independent predictors of
      PD-L1 expression. CONCLUSION: PD-L1 expression was related to high glucose
      metabolism in small-sized NSCLC.

PMID- 29187499
TI  - Anastomotic Leakage Using Linear Stapling Device with Pre-attached Bioabsorbable
      Polyglycolic Acid Felt After Laparoscopic Anterior Resection.
AB  - AIM: Many studies have evaluated the risk factors for anastomotic leakage after
      laparoscopic anterior resection. In this study in order to increase the tightness
      of anastomoses and prevent bleeding from their staple lines, a linear stapler
      with pre-attached bioabsorbable polyglycolic acid (PGA) felt was used for rectal
      transection, and the short-term surgical outcomes were evaluated. PATIENTS AND
      METHODS: A prospective registry of 62 patients with rectosigmoidal or rectal
      carcinoma who initially underwent laparoscopic anterior resection using PGA felt
      for rectal transection was reviewed. RESULTS: The overall frequency of
      anastomotic leakage was 1.6% (1/62), and none of the patients developed
      postoperative staple line bleeding or other adverse events related to the use of
      PGA felt. CONCLUSION: The frequency of anastomotic leakage was relatively low,
      and therefore the use of a linear stapler with pre-attached bioabsorbable PGA
      felt might reduce the risk of adverse events related to anastomosis, especially
      anastomotic leakage.

PMID- 29187500
TI  - Robotic-assisted Transperitoneal Infrarenal Para-aortic Lymphadenectomy for
      Gynecological Malignancies: Comparison with a Laparoscopic Approach.
AB  - BACKGROUND/AIM: We evaluated the clinical feasibility and surgical outcomes of
      robotic-assisted transperitoneal infrarenal para-aortic lymphadenectomy (TIPAL)
      in patients with gynecological malignancies. PATIENTS AND METHODS: The
      perioperative outcomes in 90 patients with gynecological malignancies who
      underwent laparoscopic (n=43) or robotic-assisted (n=47) TIPAL were compared
      retrospectively. RESULTS: The operative time for pelvic and total lymphadenectomy
      were significantly shorter in the robotic-assisted approach, whereas the time for
      infrarenal para-aortic lymphadenectomy did not differ statistically. In contrast,
      the number of infrarenal para-aortic lymph nodes was significantly higher in the
      robotic-assisted approach. We compared the time per retrieved lymph node in both
      approaches, and those for pelvic, infrarenal para-aortic, and total
      lymphadenectomy were significantly shorter in the robotic-assisted approach.
      CONCLUSION: In our study, the robotic-assisted TIPAL took less time to retrieve a
      lymph node than the laparoscopic approach. The robotic-assisted approach for
      TIPAL is feasible for the staging and treatment of patients with gynecological
      malignancies.

PMID- 29187501
TI  - Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy
      for Patients with Resectable Synchronous Colon Cancer and Liver-confined
      Metastases: A Nationwide Database Study.
AB  - BACKGROUND: Although irinotecan and oxaliplatin are both standard treatments for
      advanced colon cancer, it remains unknown whether either is effective for
      patients with resectable synchronous colon cancer and liver-confined metastasis
      (SCCLM) after curative surgery. PATIENTS AND METHODS: A population-based cohort
      of patients diagnosed with de novo SCCLM between 2004 and 2009 was established by
      searching the database of the Taiwan Cancer Registry and the National Health
      Insurance Research Database of Taiwan. Patients who underwent curative surgery as
      their first therapy followed by chemotherapy doublets were classified into the
      irinotecan group or oxaliplatin group accordingly. Patients who received
      radiotherapy or did not receive chemotherapy doublets were excluded. RESULTS: We
      included 6,533 patients with de novo stage IV colon cancer. Three hundred and
      nine of them received chemotherapy doublets after surgery; 77 patients received
      irinotecan and 232 patients received oxaliplatin as adjuvant chemotherapy. The
      patients in both groups exhibited similar overall survival (median: not reached
      vs. 40.8 months, p=0.151) and time to the next line of treatment (median: 16.5
      vs. 14.3 months, p=0.349) in both univariate and multivariate analyses.
      Additionally, patients with resectable SCCLM had significantly shorter median
      overall survival than patients with stage III colon cancer who underwent curative
      surgery and subsequent adjuvant chemotherapy, but longer median overall survival
      than patients with de novo stage IV colon cancer who underwent surgery only at
      the primary site followed by standard systemic chemotherapy (p<0.001).
      CONCLUSION: Irinotecan and oxaliplatin exhibited similar efficacy in patients who
      underwent curative surgery for resectable SCCLM.

PMID- 29187502
TI  - Errata.

PMID- 29187504
TI  - Tissue-Specific Gene Inactivation in Xenopus laevis: Knockout of lhx1 in the
      Kidney with CRISPR/Cas9.
AB  - Studying genes involved in organogenesis is often difficult because many of these
      genes are also essential for early development. The allotetraploid frog, Xenopus
      laevis, is commonly used to study developmental processes, but because of the
      presence of two homeologs for many genes, it has been difficult to use as a
      genetic model. Few studies have successfully used CRISPR in amphibians, and
      currently there is no tissue-targeted knockout strategy described in Xenopus The
      goal of this study is to determine whether CRISPR/Cas9-mediated gene knockout can
      be targeted to the Xenopus kidney without perturbing essential early gene
      function. We demonstrate that targeting CRISPR gene editing to the kidney and the
      eye of F0 embryos is feasible. Our study shows that knockout of both homeologs of
      lhx1 results in the disruption of kidney development and function but does not
      lead to early developmental defects. Therefore, targeting of CRISPR to the kidney
      may not be necessary to bypass the early developmental defects reported upon
      disruption of Lhx1 protein expression or function by morpholinos, antisense RNA,
      or dominant negative constructs. We also establish a control for CRISPR in
      Xenopus by editing a gene (slc45a2) that when knocked out results in albinism
      without altering kidney development. This study establishes the feasibility of
      tissue-specific gene knockout in Xenopus, providing a cost-effective and
      efficient method for assessing the roles of genes implicated in developmental
      abnormalities that is amenable to high-throughput gene or drug screening
      techniques.

PMID- 29187505
TI  - A Common Pathway of Root Growth Control and Response to CLE Peptides Through Two
      Receptor Kinases in Arabidopsis.
AB  - Cell-cell communication is essential for plants to integrate developmental
      programs with external cues that affect their growth. Recent advances in plant
      signaling have uncovered similar molecular mechanisms in shoot, root, and
      vascular meristem signaling that involve receptor-like kinases and small,
      secreted peptides. Here, we report that the receptor-like kinases TOAD2/RPK2 and
      RPK1 regulate root growth by controlling cell proliferation and affecting
      meristem size. Two types of developmental alterations were observed upon
      exogenous CLE peptide application. The first type was detected in all plants
      treated, and comprise increased proliferative activity of cells in the stem cell
      niche and a delay of progression in differentiation of daughter cells. The second
      type was changes specific to the genotypes that are sensitive to CLE-driven root
      meristem inhibition and include a large decrease in the occurrence of cell
      divisions in longitudinal files, correlating with shorter meristems and cessation
      of root growth. The root meristems of toad2/rpk2 mutant plants are insensitive to
      the inhibitory effect of CLE17 peptide treatment, consistent with TOAD2/RPK2
      function as a receptor for CLE peptides. In addition, a strong reduction in the
      expression of RPK1 protein upon CLE treatment, dependent on TOAD2/RPK2, suggests
      that these two RLKs mediate CLE signaling in a common pathway to control root
      growth.

PMID- 29187506
TI  - Cooperative Control of Ecdysone Biosynthesis in Drosophila by Transcription
      Factors Seance, Ouija Board, and Molting Defective.
AB  - Ecdysteroids are steroid hormones that control many aspects of development and
      physiology. During larval development, ecdysone is synthesized in an endocrine
      organ called the prothoracic gland through a series of ecdysteroidogenic enzymes
      encoded by the Halloween genes. The expression of the Halloween genes is highly
      restricted and dynamic, indicating that their spatiotemporal regulation is
      mediated by their tight transcriptional control. In this study, we report that
      three zinc finger-associated domain (ZAD)-C2H2 zinc finger transcription factors
      Seance (Sean), Ouija board (Ouib), and Molting defective (Mld)-cooperatively
      control ecdysone biosynthesis in the fruit fly Drosophila melanogaster Sean and
      Ouib act in cooperation with Mld to positively regulate the transcription of
      neverland and spookier, respectively, two Halloween genes. Remarkably, loss-of
      function mutations in sean, ouib, or mld can be rescued by the expression of
      neverland, spookier, or both, respectively. These results suggest that the three
      transcription factors have distinct roles in coordinating the expression of just
      two genes in Drosophila Given that neverland and spookier are located in
      constitutive heterochromatin, Sean, Ouib, and Mld represent the first example of
      a transcription factor subset that regulates genes located in constitutive
      heterochromatin.

PMID- 29187507
TI  - Using Separation-of-Function Mutagenesis To Define the Full Spectrum of
      Activities Performed by the Est1 Telomerase Subunit in Vivo.
AB  - A leading objective in biology is to identify the complete set of activities that
      each gene performs in vivo In this study, we have asked whether a genetic
      approach can provide an efficient means of achieving this goal, through the
      identification and analysis of a comprehensive set of separation-of-function (sof
      ) mutations in a gene. Toward this goal, we have subjected the Saccharomyces
      cerevisiae EST1 gene, which encodes a regulatory subunit of telomerase, to
      intensive mutagenesis (with an average coverage of one mutation for every 4.5
      residues), using strategies that eliminated those mutations that disrupted
      protein folding/stability. The resulting set of sof- mutations defined four
      biochemically distinct activities for the Est1 telomerase protein: two temporally
      separable steps in telomerase holoenzyme assembly, a telomerase recruitment
      activity, and a fourth newly discovered regulatory function. Although
      biochemically distinct, impairment of each of these four different activities
      nevertheless conferred a common phenotype (critically short telomeres) comparable
      to that of an est1-? null strain. This highlights the limitations of gene
      deletions, even for nonessential genes; we suggest that employing a
      representative set of sof- mutations for each gene in future high- and low
      throughput investigations will provide deeper insights into how proteins interact
      inside the cell.

PMID- 29187509
TI  - The spectrum, incidence, kinetics and management of endocrinopathies with immune
      checkpoint inhibitors for metastatic melanoma.
AB  - OBJECTIVE: Endocrine immune-related adverse events (endocrinopathies) are
      increasingly prevalent with the use of immune checkpoint inhibitors for the
      treatment of metastatic melanoma and other malignancies. There are no evidence
      based guidelines for the screening or management of such patients. To describe
      the spectrum, incidence, kinetics and management of endocrinopathies with immune
      checkpoint inhibitors. DESIGN: A prospective study conducted at Melanoma
      Institute Australia between April 2014 and October 2015. METHODS: A total of 177
      patients were treated with (a) ipilimumab (n = 15), (b) anti-PD-1 (nivolumab,
      pembrolizumab) (n = 103) or (c) combination ipilimumab and anti-PD-1 (n = 59) and
      were screened and managed for the subsequent endocrinopathies. The main outcome
      measures were the incidence and kinetics of endocrinopathy by immunotherapy drug
      class. RESULTS: Thirty-one patients (18%) developed an endocrine immune-related
      adverse event (thyroid dysfunction: 14%, hypophysitis: 6% and autoimmune
      diabetes: 0.6%). Combination immunotherapy was more likely to result in a single
      or multiple endocrinopathy compared to anti-PD-1 monotherapy (27% vs 9% and 7% vs
      0% respectively, P < 0.01). Endocrinopathies occurred after a median of 8 weeks
      from treatment commencement (range: 12-225 days), with combination immunotherapy
      resulting in significantly earlier onset compared to ipilimumab (median: 30 vs 76
      days, P = 0.046). The majority of endocrinopathies were identified in
      asymptomatic patients with hormonal screening. There were no baseline predictors
      for endocrinopathy. CONCLUSIONS: Combination immunotherapy has a greater risk of
      development of endocrinopathy compared to anti-PD-1 monotherapy. Regular
      biochemical profiling of patients, particularly within the first twelve weeks,
      results in early detection of endocrinopathy to minimise morbidity.

PMID- 29187508
TI  - Relaxed Selection During a Recent Human Expansion.
AB  - Humans have colonized the planet through a series of range expansions, which
      deeply impacted genetic diversity in newly settled areas and potentially
      increased the frequency of deleterious mutations on expanding wave fronts. To
      test this prediction, we studied the genomic diversity of French Canadians who
      colonized Quebec in the 17th century. We used historical information and records
      from ~4000 ascending genealogies to select individuals whose ancestors lived
      mostly on the colonizing wave front and individuals whose ancestors remained in
      the core of the settlement. Comparison of exomic diversity reveals that: (i) both
      new and low-frequency variants are significantly more deleterious in front than
      in core individuals, (ii) equally deleterious mutations are at higher frequencies
      in front individuals, and (iii) front individuals are two times more likely to be
      homozygous for rare very deleterious mutations present in Europeans. These
      differences have emerged in the past six to nine generations and cannot be
      explained by differential inbreeding, but are consistent with relaxed selection
      mainly due to higher rates of genetic drift on the wave front. Demographic
      inference and modeling of the evolution of rare variants suggest lower effective
      size on the front, and lead to an estimation of selection coefficients that
      increase with conservation scores. Even though range expansions have had a
      relatively limited impact on the overall fitness of French Canadians, they could
      explain the higher prevalence of recessive genetic diseases in recently settled
      regions of Quebec.

PMID- 29187510
TI  - ERCC1 as predictive biomarker to platinum-based chemotherapy in adrenocortical
      carcinomas.
AB  - OBJECTIVE: Platinum-based chemotherapy (PBC) is the most effective cytotoxic
      treatment for advanced adrenocortical carcinoma (ACC). Excision repair cross
      complementing group 1 (ERCC1) plays a critical role in the repair of platinum
      induced DNA damage. Two studies investigating the role of ERCC1 immunostaining as
      a predictive marker for the response to PBC in ACC had reported conflicting
      results. Both studies used the ERCC1-antibody clone 8F1 that later turned out to
      be not specific. The aim of this study was to evaluate the predictive role of
      ERCC1 with a new specific antibody in a larger series of ACC. DESIGN AND METHODS:
      146 ACC patients with available FFPE slides were investigated. All patients
      underwent PBC (median cycles = 6), including cisplatin (n = 131) or carboplatin
      (n = 15), in most cases combined with etoposide (n = 144), doxorubicin (n = 131)
      and mitotane (n = 131). Immunostaining was performed with the novel ERCC1
      antibody clone 4F9. The relationship between ERCC1 expression and
      clinicopathological parameters, as well as best objective response to therapy and
      progression-free survival (PFS) during PBC was evaluated. RESULTS: High ERCC1
      expression was observed in 66% of ACC samples. During PBC, 43 patients
      experienced objective response (29.5%), 49 stable disease (33.6%), 8 mixed
      response (5.5%) and 46 progressive disease (31.5%) without any relationship with
      the ERCC1 immunostaining. No significant correlation was also found between ERCC1
      expression and progression-free survival (median 6.5 vs 6 months, P  =  0.33, HR
      = 1.23, 95% CI = 0.82-2.0). CONCLUSION: ERCC1 expression is not directly
      associated with sensitivity to PBC in ACC. Thus, other predictive biomarkers are
      required to support treatment decisions in patients with ACC.

PMID- 29187511
TI  - Pregnancy outcomes are not altered by variation in thyroid function within the
      normal range in women free of thyroid disease.
AB  - OBJECTIVE: In the recently revised guidelines on the management of thyroid
      dysfunction during pregnancy, treatment with thyroid hormone (LT4) is not
      recommended in women without thyroid autoimmunity (TAI) and TSH levels in the
      range 2.5-4.0 mIU/L, and in a recent study in that particular group of pregnant
      women, more complications were observed when a treatment with LT4 was given. The
      objective of the study was therefore to investigate whether variation in thyroid
      function within the normal (non-pregnant) range in women free of thyroid disease
      was associated with altered pregnancy outcomes? DESIGN: Cross-sectional data
      analysis of 1321 pregnant women nested within an ongoing prospective collection
      of pregnant women's data in a single centre in Brussels, Belgium. METHODS:
      Thyroid peroxidase antibodies (TPO-abs), thyroid-stimulating hormone (TSH), free
      T4 (FT4) and ferritin levels were measured and baseline characteristics were
      recorded. Women taking LT4, with TAI and thyroid function outside the normal non
      pregnant range were excluded. Pregnancy outcomes and baseline characteristics
      were correlated with all TSH and FT4 levels within the normal range and compared
      between two groups (TSH cut-off < and >=2.5 mIU/L). RESULTS: Tobacco use was
      associated with higher serum TSH levels (OR: 1.38; CI 95%: 1.08-1.74); P = 0.009.
      FT4 levels were inversely correlated with age and BMI (rho = -0.096 and -0.089; P
      < 0.001 and 0.001 respectively) and positively correlated with ferritin levels
      (rho = 0.097; P < 0.001). Postpartum haemorrhage (>500 mL) was inversely
      associated with serum FT4 levels (OR: 0.35; CI 95%: 0.13-0.96); P = 0.040. Also
      10% of women free of thyroid disease had serum TSH levels >=2.5 mIU/L.
      CONCLUSIONS: Variation in thyroid function during the first trimester within the
      normal (non-pregnant) range in women free of thyroid disease was not associated
      with altered pregnancy outcomes. These results add evidence to the recommendation
      against LT4 treatment in pregnant women with high normal TSH levels and without
      TPO antibodies.

PMID- 29187513
TI  - A critical evaluation of the anabolic response after bolus or continuous feeding
      in COPD and healthy older adults.
AB  - After bolus and continuous enteral feeding of the same protein, different
      digestion and absorption kinetics and anabolic responses are observed.
      Establishing which mode of feeding has the highest anabolic potential in patients
      with chronic obstructive pulmonary disease (COPD) may aid in the prevention of
      muscle wasting, but an important confounding factor is the duration of
      assessments after bolus feeding. We hypothesized that the anabolic response to
      bolus and continuous feeding in COPD patients is comparable when methodological
      issues are addressed. Twenty-one older adults (12 patients with stage II-IV COPD
      and 9 healthy controls) were studied after intake of a fast-absorbing hydrolyzed
      casein protein-carbohydrate mixture either as a single bolus or as small sips
      (crossover design). Whole body protein synthesis (PS), breakdown (PB), net PS (PS
      - PB) protein efficiency (netPSPE), net protein balance (phenylalanine (PHE)
      intake - PHE hydroxylation) protein efficiency (netBalPE), and splanchnic PHE
      extraction (SPEPHE) were assessed using stable isotope tracer methodology. Bolus
      feeding assessments were done at 90, 95, and 99% of the calculated duration of
      the anabolic response. At 99%, netBalPE was higher for sip feeding than bolus
      feeding in both groups (P<0.0001). Nevertheless, bolus feeding was associated
      with a lower SPEPHE (P<0.0001) and higher netPSPE (P<0.0001). At 90% compared
      with 99%, PS and netBalPE after bolus feeding was significantly overestimated. In
      conclusion, several factors complicate a comparison of the anabolic capacity of
      bolus and continuous feeding in acute studies, including the critical role of SPE
      calculation and assumptions, and the duration of postprandial assessments after
      bolus feeding.

PMID- 29187512
TI  - Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a
      large intragenic in-frame DICER1 deletion.
AB  - OBJECTIVE: Familial multinodular goiter (MNG), with or without ovarian Sertoli
      Leydig cell tumor (SLCT), has been linked to DICER1 syndrome. We aimed to search
      for the presence of a germline DICER1 mutation in a large family with a
      remarkable history of MNG and SLCT, and to further explore the relevance of the
      identified mutation. DESIGN AND METHODS: Sanger sequencing, Fluidigm Access Array
      and multiplex ligation-dependent probe amplification (MLPA) techniques were used
      to screen for DICER1 mutations in germline DNA from 16 family members. Where
      available, tumor DNA was also studied. mRNA and protein extracted from carriers'
      lymphocytes were used to characterize the expression of the mutant DICER1.
      RESULTS: Nine of 16 tested individuals carried a germline, in-frame DICER1
      deletion (c.4207-41_5364+1034del), which resulted in the loss of exons 23 and 24
      from the cDNA. The mutant transcript does not undergo nonsense-mediated decay and
      the protein is devoid of specific metal ion-binding amino acids (p.E1705 and
      p.D1709) in the RNase IIIb domain. In addition, characteristic somatic 'second
      hit' mutations in this region were found on the other allele in tumors.
      CONCLUSIONS: Patients with DICER1 syndrome usually present a combination of a
      typically truncating germline DICER1 mutation and a tumor-specific hotspot
      missense mutation within the sequence encoding the RNase IIIb domain. The in
      frame deletion found in this family suggests that the germline absence of p.E1705
      and p.D1709, which are crucial for RNase IIIb activity, may be enough to permit
      DICER1 syndrome to occur.

PMID- 29187514
TI  - Lending a hand: could machine learning help hospital staff make better use of
      patient feedback?

PMID- 29187517
TI  - "Pinball" intrusions in spinocerebellar ataxia type 3.

PMID- 29187516
TI  - Amyloid-Like beta-Aggregates as Force-Sensitive Switches in Fungal Biofilms and
      Infections.
AB  - Cellular aggregation is an essential step in the formation of biofilms, which
      promote fungal survival and persistence in hosts. In many of the known yeast cell
      adhesion proteins, there are amino acid sequences predicted to form amyloid-like
      beta-aggregates. These sequences mediate amyloid formation in vitro. In vivo,
      these sequences mediate a phase transition from a disordered state to a partially
      ordered state to create patches of adhesins on the cell surface. These beta
      aggregated protein patches are called adhesin nanodomains, and their presence
      greatly increases and strengthens cell-cell interactions in fungal cell
      aggregation. Nanodomain formation is slow (with molecular response in minutes and
      the consequences being evident for hours), and strong interactions lead to
      enhanced biofilm formation. Unique among functional amyloids, fungal adhesin beta
      aggregation can be triggered by the application of physical shear force, leading
      to cellular responses to flow-induced stress and the formation of robust biofilms
      that persist under flow. Bioinformatics analysis suggests that this phenomenon
      may be widespread. Analysis of fungal abscesses shows the presence of surface
      amyloids in situ, a finding which supports the idea that phase changes to an
      amyloid-like state occur in vivo. The amyloid-coated fungi bind the damage
      associated molecular pattern receptor serum amyloid P component, and there may be
      a consequential modulation of innate immune responses to the fungi. Structural
      data now suggest mechanisms for the force-mediated induction of the phase change.
      We summarize and discuss evidence that the sequences function as triggers for
      protein aggregation and subsequent cellular aggregation, both in vitro and in
      vivo.

PMID- 29187518
TI  - Neurofascin antibodies in autoimmune, genetic, and idiopathic neuropathies.
AB  - OBJECTIVE: To measure the frequency, persistence, isoform specificity, and
      clinical correlates of neurofascin antibodies in patients with peripheral
      neuropathies. METHODS: We studied cohorts of patients with Guillain-Barre
      syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) (n =
      59), genetic neuropathy (n = 111), and idiopathic neuropathy (n = 43) for
      immunoglobulin (Ig) G and IgM responses to 3 neurofascin (NF) isoforms (NF140,
      NF155, and NF186) using cell-based assays. RESULTS: Neurofascin antibodies were
      more common in patients with GBS/CIDP (14%, 8 of 59) compared to genetic
      neuropathy controls (3%, 3 of 111, p = 0.01). Seven percent (3 of 43) of patients
      with idiopathic neuropathy also had neurofascin antibodies. NF155 IgG4 antibodies
      were associated with CIDP refractory to IV immunoglobulin but responsive to
      rituximab, and some of these patients had an acute onset resembling GBS. NF186
      IgG and IgM to either isoform were less specific. A severe form of CIDP,
      approaching a locked-in state, was seen in a patient with antibodies recognizing
      all 3 neurofascin isoforms. CONCLUSIONS: Neurofascin antibodies were 4 times more
      frequent in autoimmune neuropathy samples compared to genetic neuropathy
      controls. Persistent IgG4 responses to NF155 correlated with severe CIDP
      resistant to usual treatments but responsive to rituximab. IgG4 antibodies
      against the common domains shared by glial and axonal isoforms may portend a
      particularly severe but treatable neuropathy. The prognostic implications of
      neurofascin antibodies in a subset of idiopathic neuropathy patients and
      transient IgM responses in GBS require further investigation.

PMID- 29187515
TI  - Nrf2 at the heart of oxidative stress and cardiac protection.
AB  - The NFE2L2 gene encodes the transcription factor Nrf2 best known for regulating
      the expression of antioxidant and detoxification genes. Gene knockout approaches
      have demonstrated its universal cytoprotective features. While Nrf2 has been the
      topic of intensive research in cancer biology since its discovery in 1994,
      understanding the role of Nrf2 in cardiovascular disease has just begun. The
      literature concerning Nrf2 in experimental models of atherosclerosis, ischemia,
      reperfusion, cardiac hypertrophy, heart failure, and diabetes supports its
      cardiac protective character. In addition to antioxidant and detoxification
      genes, Nrf2 has been found to regulate genes participating in cell signaling,
      transcription, anabolic metabolism, autophagy, cell proliferation, extracellular
      matrix remodeling, and organ development, suggesting that Nrf2 governs damage
      resistance as well as wound repair and tissue remodeling. A long list of small
      molecules, most derived from natural products, have been characterized as Nrf2
      inducers. These compounds disrupt Keap1-mediated Nrf2 ubquitination, thereby
      prohibiting proteasomal degradation and allowing Nrf2 protein to accumulate and
      translocate to the nucleus, where Nrf2 interacts with sMaf to bind to ARE in the
      promoter of genes. Recently alternative mechanisms driving Nrf2 protein increase
      have been revealed, including removal of Keap1 by autophagy due to p62/SQSTM1
      binding, inhibition of betaTrCP or Synoviolin/Hrd1-mediated ubiquitination of
      Nrf2, and de novo Nrf2 protein translation. We review here a large volume of
      literature reporting historical and recent discoveries about the function and
      regulation of Nrf2 gene. Multiple lines of evidence presented here support the
      potential of dialing up the Nrf2 pathway for cardiac protection in the clinic.

PMID- 29187520
TI  - Investigation of specific interactions between T7 promoter and T7 RNA polymerase
      by force spectroscopy using atomic force microscope.
AB  - The specific recognition and binding of promoter and RNA polymerase is the first
      step of transcription initiation in bacteria and largely determines transcription
      activity. Therefore, direct analysis of the interaction between promoter and RNA
      polymerase in vitro may be a new strategy for promoter characterization, to avoid
      interference due to the cell's biophysical condition and other regulatory
      elements. In the present study, the specific interaction between T7 promoter and
      T7 RNA polymerase was studied as a model system using force spectroscopy based on
      atomic force microscope (AFM). The specific interaction between T7 promoter and
      T7 RNA polymerase was verified by control experiments, and the rupture force in
      this system was measured as 307.2 +/- 6.7 pN. The binding between T7 promoter
      mutants with various promoter activities and T7 RNA polymerase was analyzed.
      Interaction information including rupture force, rupture distance and binding
      percentage were obtained in vitro, and reporter gene expression regulated by
      these promoters was also measured according to a traditional promoter activity
      characterization method in vivo Using correlation analysis, it was found that the
      promoter strength characterized by reporter gene expression was closely
      correlated with rupture force and the binding percentage by force spectroscopy.
      These results indicated that the analysis of the interaction between promoter and
      RNA polymerase using AFM-based force spectroscopy was an effective and valid
      approach for the quantitative characterization of promoters.

PMID- 29187519
TI  - Proteomics Reveals the Molecular Underpinnings of Stronger Learning and Memory in
      Eastern Compared to Western Bees.
AB  - The eastern (Apis cerana cerana, Acc) and western (Apis mellifera ligustica, Aml)
      honeybee are two major honeybee species. Surprisingly, little is known about the
      fundamental molecular neurobiology of brain suborgans of Acc and Aml. We
      characterized and compared the proteomes of mushroom bodies (MBs), antennal lobes
      (ALs) and optical lobes (OLs) in the brain of both species, and biologically
      validated the functions related to learning and memory. Acc and Aml have evolved
      similar proteome signatures in MBs and OLs to drive the domain-specific neural
      activities. In MBs of both species, commonly enriched and enhanced functional
      groups related to protein metabolism and Ca2+ transport relative to ALs and OLs,
      suggests that proteins and Ca2+ are vital for consolidating learning and memory
      via modulation of synaptic structure and signal transduction. Furthermore, in OLs
      of both species, the mainly enriched ribonucleoside metabolism suggests its vital
      role as second messenger in promoting phototransduction. Notably, in ALs of both
      species, distinct proteome settings have shaped to prime olfactory learning and
      memory. In ALs of Acc, this is supported by the enriched cytoskeleton
      organization to sustain olfactory signaling through modulation of plasticity in
      glomeruli and intracellular transport. In ALs of Aml, however, the enriched
      functional groups implicated in hydrogen ion transport are indicative of their
      importance in supporting olfactory processes by regulation of synaptic
      transmission. The biological confirmation of enhanced activities of protein
      metabolism and signal transduction in ALs and MBs of Acc relative to in Aml
      demonstrates that a stronger sense of olfactory learning and memory has evolved
      in Acc. The reported first in-depth proteome data of honeybee brain suborgans
      provide a novel insight into the molecular basis of neurobiology, and is
      potentially useful for further neurological studies in honeybees and other
      insects.

PMID- 29187521
TI  - Plant DHDPR forms a dimer with unique secondary structure features that preclude
      higher-order assembly.
AB  - Dihydrodipicolinate reductase (DHDPR) catalyses the second reaction in the
      diaminopimelate pathway of lysine biosynthesis in bacteria and plants. In
      contrast with the tetrameric bacterial DHDPR enzymes, we show that DHDPR from
      Vitis vinifera (grape) and Selaginella moellendorffii are dimeric in solution. In
      the present study, we have also determined the crystal structures of DHDPR
      enzymes from the plants Arabidopsis thaliana and S. moellendorffii, which are the
      first dimeric DHDPR structures. The analysis of these models demonstrates that
      the dimer forms through the intra-strand interface, and that unique secondary
      features in the plant enzymes block tetramer assembly. In addition, we have also
      solved the structure of tetrameric DHDPR from the pathogenic bacteria Neisseria
      meningitidis Measuring the activity of plant DHDPR enzymes showed that they are
      much more prone to substrate inhibition than the bacterial enzymes, which appears
      to be a consequence of increased flexibility of the substrate-binding loop and
      higher affinity for the nucleotide substrate. This higher propensity to substrate
      inhibition may have consequences for ongoing efforts to increase lysine
      biosynthesis in plants.

PMID- 29187522
TI  - Surgical academic reach: the higher degree effect quantified.
AB  - INTRODUCTION: Proof of professional specific academic attainment is embedded
      within the Joint Committee on Surgical Training 2013 general surgery curriculum,
      mandating that all higher general surgical trainees (HST) obtain three peer
      reviewed publications to qualify for Certification of Completion of Training.
      Yet, Modernising Medical Careers (MMC) has been associated with a trend away from
      the gold standard postgraduate credentials of higher degrees by research. This
      study aimed to evaluate the academic achievements of a post-MMC UK Deanery HST
      cohort to determine what additional benefits higher degree study might confer.
      METHOD: The Scopus bibliographic database (Elsevier, RELX Group) was used to
      characterise the academic profiles of 101 consecutive HSTs and supplemented with
      Intercollegiate Surgical Programme Curriculum data. Primary outcome measures were
      numbers of publications, citations and Hirsch indices (HI). RESULTS: Thirty-seven
      HSTs (36.6%) had been awarded higher degrees (29 Doctor of Medicine, 8 Doctor of
      Philosophy). Academic profiles of HSTs with higher degrees were stronger than
      those of HSTs without, specifically: median (range) publication numbers 16 (2-57)
      vs 2 (0-11, P<0.001), citations 93 (0-1600) vs 6 (0-132, P<0.001), first author
      publications 6 (0-33) vs 3 (0-106, P<0.001), communications to learnt societies
      30 (5-79) vs 8 (2-35, P<0.001) and HI 6 (1-26) vs 1 (0-6, P<0.001). CONCLUSION:
      Proof of academic reach by higher degree was associated with important enhanced
      professional credentials, strengthening HIs sixfold. Trainers and trainees alike
      should be aware of the relative magnitude of such benefits when planning
      educational programmes.

PMID- 29187523
TI  - Modeling hypercholesterolemia and vascular lipid accumulation in LDL receptor
      mutant zebrafish.
AB  - Elevated plasma LDL cholesterol is the dominant risk factor for the development
      of atherosclerosis and cardiovascular disease. Deficiency in the LDL receptor
      (LDLR) is a major cause of familial hypercholesterolemia in humans, and the LDLR
      knockout mouse is a major animal model of atherosclerosis. Here we report the
      generation and characterization of an ldlr mutant zebrafish as a new animal model
      to study hypercholesterolemia and vascular lipid accumulation, an early event in
      the development of human atherosclerosis. The ldlr mutant zebrafish were
      characterized by activated SREBP-2 pathway and developed moderate
      hypercholesterolemia when fed a normal diet. However, a short-term, 5-day feeding
      of ldlr mutant larvae with a high-cholesterol diet (HCD) resulted in exacerbated
      hypercholesterolemia and accumulation of vascular lipid deposits. Lomitapide, an
      inhibitor of apoB lipoprotein secretion, but not the antioxidant probucol,
      significantly reduced accumulation of vascular lipid deposits in HCD-fed ldlr
      mutant larvae. Furthermore, ldlr mutants were defective in hepatic clearance of
      lipopolysaccharides, resulting in reduced survival. Taken together, our data
      suggest that the ldlr knockout zebra-fish is a versatile model for studying the
      function of the LDL receptor, hypercholesterolemia, and related vascular
      pathology in the context of early atherosclerosis.

PMID- 29187524
TI  - dTBC1D7 regulates systemic growth independently of TSC through insulin signaling.
AB  - The insulin signaling pathway plays key roles in systemic growth. TBC1D7 has
      recently been identified as the third subunit of the tuberous sclerosis complex
      (TSC), a negative regulator of cell growth. Here, we used Drosophila as a model
      system to dissect the physiological function of TBC1D7 in vivo. In mutants
      lacking TBC1D7, cell and organ growth were promoted, and TBC1D7 limited cell
      growth in a cell-nonautonomous and TSC-independent manner. TBC1D7 is specifically
      expressed in insulin-producing cells in the fly brain and regulated biosynthesis
      and release of insulin-like peptide 2, leading to systemic growth. Furthermore,
      animals carrying the dTBC1D7 mutation were hypoglycemic, short-lived, and
      sensitive to oxidative stress. Our findings provide new insights into the
      physiological function of TBC1D7 in the systemic control of growth, as well as
      insights into human disorders caused by TBC1D7 mutation.

PMID- 29187525
TI  - Humanin is an endogenous activator of chaperone-mediated autophagy.
AB  - Chaperone-mediated autophagy (CMA) serves as quality control during stress
      conditions through selective degradation of cytosolic proteins in lysosomes.
      Humanin (HN) is a mitochondria-associated peptide that offers cytoprotective,
      cardioprotective, and neuroprotective effects in vivo and in vitro. In this
      study, we demonstrate that HN directly activates CMA by increasing substrate
      binding and translocation into lysosomes. The potent HN analogue HNG protects
      from stressor-induced cell death in fibroblasts, cardiomyoblasts, neuronal cells,
      and primary cardiomyocytes. The protective effects are lost in CMA-deficient
      cells, suggesting that they are mediated through the activation of CMA. We
      identified that a fraction of endogenous HN is present at the cytosolic side of
      the lysosomal membrane, where it interacts with heat shock protein 90 (HSP90) and
      stabilizes binding of this chaperone to CMA substrates as they bind to the
      membrane. Inhibition of HSP90 blocks the effect of HNG on substrate translocation
      and abolishes the cytoprotective effects. Our study provides a novel mechanism by
      which HN exerts its cardioprotective and neuroprotective effects.

PMID- 29187526
TI  - Aurora A kinase phosphorylates Hec1 to regulate metaphase kinetochore-microtubule
      dynamics.
AB  - Precise regulation of kinetochore-microtubule attachments is essential for
      successful chromosome segregation. Central to this regulation is Aurora B kinase,
      which phosphorylates kinetochore substrates to promote microtubule turnover. A
      critical target of Aurora B is the N-terminal "tail" domain of Hec1, which is a
      component of the NDC80 complex, a force-transducing link between kinetochores and
      microtubules. Although Aurora B is regarded as the "master regulator" of
      kinetochore-microtubule attachment, other mitotic kinases likely contribute to
      Hec1 phosphorylation. In this study, we demonstrate that Aurora A kinase
      regulates kinetochore-microtubule dynamics of metaphase chromosomes, and we
      identify Hec1 S69, a previously uncharacterized phosphorylation target site in
      the Hec1 tail, as a critical Aurora A substrate for this regulation.
      Additionally, we demonstrate that Aurora A kinase associates with inner
      centromere protein (INCENP) during mitosis and that INCENP is competent to drive
      accumulation of the kinase to the centromere region of mitotic chromosomes. These
      findings reveal that both Aurora A and B contribute to kinetochore-microtubule
      attachment dynamics, and they uncover an unexpected role for Aurora A in late
      mitosis.

PMID- 29187527
TI  - Identification of seipin-linked factors that act as determinants of a lipid
      droplet subpopulation.
AB  - Functional heterogeneity within the lipid droplet (LD) pool of a single cell has
      been observed, yet the underlying mechanisms remain enigmatic. Here, we report on
      identification of a specialized LD subpopulation characterized by a unique
      proteome and a defined geographical location at the nucleus-vacuole junction
      contact site. In search for factors determining identity of these LDs, we
      screened ~6,000 yeast mutants for loss of targeting of the subpopulation marker
      Pdr16 and identified Ldo45 (LD organization protein of 45 kD) as a crucial
      targeting determinant. Ldo45 is the product of a splicing event connecting two
      adjacent genes (YMR147W and YMR148W/OSW5/LDO16). We show that Ldo proteins
      cooperate with the LD biogenesis component seipin and establish LD identity by
      defining positioning and surface-protein composition. Our studies suggest a
      mechanism to establish functional differentiation of organelles, opening the door
      to better understanding of metabolic decisions in cells.

PMID- 29187528
TI  - Regulation of lipid droplets by metabolically controlled Ldo isoforms.
AB  - Storage and consumption of neutral lipids in lipid droplets (LDs) are essential
      for energy homeostasis and tightly coupled to cellular metabolism. However, how
      metabolic cues are integrated in the life cycle of LDs is unclear. In this study,
      we characterize the function of Ldo16 and Ldo45, two splicing isoforms of the
      same protein in budding yeast. We show that Ldo proteins interact with the seipin
      complex, which regulates contacts between LDs and the endoplasmic reticulum (ER).
      Moreover, we show that the levels of Ldo16 and Ldo45 depend on the growth stage
      of cells and that deregulation of their relative abundance alters LD morphology,
      protein localization, and triglyceride content. Finally, we show that absence of
      Ldo proteins results in defects in LD morphology and consumption by lipophagy.
      Our findings support a model in which Ldo proteins modulate the activity of the
      seipin complex, thereby affecting LD properties. Moreover, we identify ER-LD
      contacts as regulatory targets coupling energy storage to cellular metabolism.

PMID- 29187529
TI  - SCWISh network is essential for survival under mechanical pressure.
AB  - Cells that proliferate within a confined environment build up mechanical
      compressive stress. For example, mechanical pressure emerges in the naturally
      space-limited tumor environment. However, little is known about how cells sense
      and respond to mechanical compression. We developed microfluidic bioreactors to
      enable the investigation of the effects of compressive stress on the growth of
      the genetically tractable model organism Saccharomyces cerevisiae We used this
      system to determine that compressive stress is partly sensed through a module
      consisting of the mucin Msb2 and the cell wall protein Sho1, which act together
      as a sensor module in one of the two major osmosensing pathways in budding yeast.
      This signal is transmitted via the MAPKKK kinase Ste11. Thus, we term this
      mechanosensitive pathway the "SMuSh" pathway, for Ste11 through Mucin/Sho1
      pathway. The SMuSh pathway delays cells in the G1 phase of the cell cycle and
      improves cell survival in response to growth-induced pressure. We also found that
      the cell wall integrity (CWI) pathway contributes to the response to mechanical
      compressive stress. These latter results are confirmed in complimentary
      experiments in Mishra et al. [Mishra R, et al. (2017) Proc Natl Acad Sci USA,
      10.1073/pnas.1709079114]. When both the SMuSh and the CWI pathways are deleted,
      cells fail to adapt to compressive stress, and all cells lyse at relatively low
      pressure when grown in confinement. Thus, we define a network that is essential
      for cell survival during growth under pressure. We term this mechanosensory
      system the SCWISh (survival through the CWI and SMuSh) network.

PMID- 29187530
TI  - Albatrosses hooked in the wind of change.

PMID- 29187531
TI  - Revised taphonomic perspective on African Plio-Pleistocene fauna.

PMID- 29187533
TI  - Vertebrate body size jumps the Wright way.

PMID- 29187532
TI  - Characterization of SPP inhibitors suppressing propagation of HCV and protozoa.
AB  - Signal peptide peptidase (SPP) is an intramembrane aspartic protease involved in
      the maturation of the core protein of hepatitis C virus (HCV). The processing of
      HCV core protein by SPP has been reported to be critical for the propagation and
      pathogenesis of HCV. Here we examined the inhibitory activity of inhibitors for
      gamma-secretase, another intramembrane cleaving protease, against SPP, and our
      findings revealed that the dibenzoazepine-type structure in the gamma-secretase
      inhibitors is critical for the inhibition of SPP. The spatial distribution showed
      that the gamma-secretase inhibitor compound YO-01027 with the dibenzoazepine
      structure exhibits potent inhibiting activity against SPP in vitro and in vivo
      through the interaction of Val223 in SPP. Treatment with this SPP inhibitor
      suppressed the maturation of core proteins of all HCV genotypes without the
      emergence of drug-resistant viruses, in contrast to the treatment with direct
      acting antivirals. YO-01027 also efficiently inhibited the propagation of
      protozoa such as Plasmodium falciparum and Toxoplasma gondii These data suggest
      that SPP is an ideal target for the development of therapeutics not only against
      chronic hepatitis C but also against protozoiasis.

PMID- 29187534
TI  - Bulk magnetic domain stability controls paleointensity fidelity.
AB  - Nonideal, nonsingle-domain magnetic grains are ubiquitous in rocks; however, they
      can have a detrimental impact on the fidelity of paleomagnetic records-in
      particular the determination of ancient magnetic field strength (paleointensity),
      a key means of understanding the evolution of the earliest geodynamo and the
      formation of the solar system. As a consequence, great effort has been expended
      to link rock magnetic behavior to paleointensity results, but with little
      quantitative success. Using the most comprehensive rock magnetic and
      paleointensity data compilations, we quantify a stability trend in hysteresis
      data that characterizes the bulk domain stability (BDS) of the magnetic carriers
      in a paleomagnetic specimen. This trend is evident in both geological and
      archeological materials that are typically used to obtain paleointensity data and
      is therefore pervasive throughout most paleomagnetic studies. Comparing this
      trend to paleointensity data from both laboratory and historical experiments
      reveals a quantitative relationship between BDS and paleointensity behavior.
      Specimens that have lower BDS values display higher curvature on the
      paleointensity analysis plot, which leads to more inaccurate results. In-field
      quantification of BDS therefore reflects low-field bulk remanence stability.
      Rapid hysteresis measurements can be used to provide a powerful quantitative
      method for preselecting paleointensity specimens and postanalyzing previous
      studies, further improving our ability to select high-fidelity recordings of
      ancient magnetic fields. BDS analyses will enhance our ability to understand the
      evolution of the geodynamo and can help in understanding many fundamental Earth
      and planetary science questions that remain shrouded in controversy.

PMID- 29187535
TI  - Transient receptor potential channel 6 regulates abnormal cardiac S-nitrosylation
      in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked disorder with dystrophin loss
      that results in skeletal and cardiac muscle weakening and early death. Loss of
      the dystrophin-sarcoglycan complex delocalizes nitric oxide synthase (NOS) to
      alter its signaling, and augments mechanosensitive intracellular Ca2+ influx. The
      latter has been coupled to hyperactivation of the nonselective cation channel,
      transient receptor potential canonical channel 6 (Trpc6), in isolated myocytes.
      As Ca2+ also activates NOS, we hypothesized that Trpc6 would help to mediate
      nitric oxide (NO) dysregulation and that this would be manifest in increased
      myocardial S-nitrosylation, a posttranslational modification increasingly
      implicated in neurodegenerative, inflammatory, and muscle disease. Using a
      recently developed dual-labeling proteomic strategy, we identified 1,276 S
      nitrosylated cysteine residues [S-nitrosothiol (SNO)] on 491 proteins in resting
      hearts from a mouse model of DMD (dmdmdx:utrn+/-). These largely consisted of
      mitochondrial proteins, metabolic regulators, and sarcomeric proteins, with 80%
      of them also modified in wild type (WT). S-nitrosylation levels, however, were
      increased in DMD. Genetic deletion of Trpc6 in this model (dmdmdx:utrn+/-:trpc6-/
      ) reversed ~70% of these changes. Trpc6 deletion also ameliorated left
      ventricular dilation, improved cardiac function, and tended to reduce fibrosis.
      Furthermore, under catecholamine stimulation, which also increases NO synthesis
      and intracellular Ca2+ along with cardiac workload, the hypernitrosylated state
      remained as it did at baseline. However, the impact of Trpc6 deletion on the SNO
      proteome became less marked. These findings reveal a role for Trpc6-mediated
      hypernitrosylation in dmdmdx:utrn+/- mice and support accumulating evidence that
      implicates nitrosative stress in cardiac and muscle disease.

PMID- 29187536
TI  - Inflammasome Antagonism by Human Parainfluenza Virus Type 3 C Protein.
AB  - Human parainfluenza virus type 3 (HPIV3) is a negative-sense single-stranded RNA
      virus belonging to the Paramyxoviridae family. HPIV3 is a lung-tropic virus
      causing airway diseases, including pneumonia, croup, and bronchiolitis, during
      infancy and childhood. The activation of the inflammasome by pathogens results in
      the production of proinflammatory cytokines such as interleukin-1beta (IL-1beta)
      during infection. Thus, the inflammasome-mediated proinflammatory response plays
      a critical role in regulating the immune response and virus clearance. The
      inflammasome is a multimeric protein complex triggering caspase-1 activation.
      Activated caspase-1 cleaves pro-IL-1beta into its mature (and active) secretory
      form. Our study revealed inflammasome activation in macrophages following HPIV3
      infection. Specifically, the activation of the NLRP3/ASC inflammasome resulted in
      the production of mature IL-1beta from HPIV3-infected cells. Furthermore, Toll
      like receptor 2 (TLR2) activation (first signal) and potassium efflux (second
      signal) constituted two cellular events mediating inflammasome activation
      following HPIV3 infection. During our studies, we surprisingly identified the
      HPIV3 C protein as an antagonist of inflammasome activation. The HPIV3 C protein
      is an accessory protein encoded by the open reading frame of the viral
      phosphoprotein (P) gene. The HPIV3 C protein interacted with the NLRP3 protein
      and blocked inflammasome activation by promoting the proteasomal degradation of
      the NLRP3 protein. Thus, our studies report NLRP3/ASC inflammasome activation by
      HPIV3 via TLR2 signaling and potassium efflux. Furthermore, we have identified
      HPIV3 C as a viral component involved in antagonizing inflammasome
      activation.IMPORTANCE Human parainfluenza virus type 3 (HPIV3) is a paramyxovirus
      that causes respiratory tract diseases during infancy and childhood. Currently,
      there is no effective vaccine or antiviral therapy for HPIV3. Therefore, in order
      to develop anti-HPIV3 agents (therapeutics and vaccines), it is important to
      study the HPIV3-host interaction during the immune response. Inflammasomes play
      an important role in the immune response. Inflammasome activation by HPIV3 has
      not been previously reported. Our studies demonstrated inflammasome activation by
      HPIV3 in macrophages. Specifically, HPIV3 activated the NLRP3/ASC inflammasome by
      TLR2 activation and potassium efflux. C proteins of paramyxoviruses are accessory
      proteins encoded by the viral phosphoprotein gene. The role of the C protein in
      inflammasome regulation was unknown. Surprisingly, our studies revealed that the
      HPIV3 C protein antagonizes inflammasome activation. In addition, we highlighted
      for the first time a mechanism utilized by paramyxovirus accessory proteins to
      block inflammasome activation. The HPIV3 C protein interacted with the NLRP3
      protein to trigger the proteasomal degradation of the NLRP3 protein.

PMID- 29187537
TI  - Host specific glycans are correlated with susceptibility to infection by
      lagoviruses, but not with their virulence.
AB  - The rabbit hemorrhagic disease virus (RHDV) and the European brown hare syndrome
      virus (EBHSV) are two lagoviruses from the family Caliciviridae that cause fatal
      diseases in two leporid genera, Oryctolagus and Lepus, respectively. In the last
      few years, several examples of host jumps of lagoviruses among leporids were
      recorded. In addition, a new pathogenic genotype of RHDV emerged and many non
      pathogenic strains of lagoviruses have been described. The molecular mechanisms
      behind host shifts and the emergence of virulence are unknown. Since RHDV uses
      glycans of the histo-blood group antigen type as attachment factors to initiate
      infection, we studied if glycan specificities of the new pathogenic RHDV
      genotype, non-pathogenic lagoviruses and EBHSV potentially play a role in
      determining host range and virulence of lagoviruses. We observed binding to A, B
      or H antigens of the histo-blood group family for all strains known to primarily
      infect European rabbits (Oryctolagus cuniculus), that have recently been
      classified as GI strains. Yet, we could not explain the emergence of virulence
      since similar glycan specificities were found between several pathogenic and non
      pathogenic strains. By contrast, EBHSV, recently classified as GII.1, bound to
      terminal beta-linked N-acetylglucosamine residues of O-glycans. Expression of
      these attachment factors in the upper respiratory and digestive tracts in three
      lagomorph species (Oryctolagus cuniculus, Lepus europaeus and Sylvilagus
      floridanus) showed species-specific patterns regarding the susceptibility to
      infection by these viruses, indicating that species-specific glycan expression is
      likely a major contributor to lagoviruses host specificity and range.IMPORTANCE
      Lagoviruses constitute a genus of the Caliciviridae family, comprising highly
      pathogenic viruses, RHDV and EBHSV, which infect rabbits and hares, respectively.
      Recently, non-pathogenic strains were discovered and new pathogenic strains have
      emerged. In addition, host jumps between lagomorphs are observed. The mechanisms
      responsible for the emergence of pathogenicity and host-species range are
      unknown. Previous studies showed that RHDV strains attach to glycans expressed in
      the upper respiratory and digestive tracts of rabbits, the likely doors of virus
      entry. Here we studied the glycan-binding properties of novel pathogenic and non
      pathogenic strains looking for a link between glycan-binding and virulence or
      between glycan specificity and host range. We found that glycan binding did not
      correlate with virulence. However, expression of glycan motifs in the upper
      respiratory and digestive tracts of lagomorphs revealed species-specific patterns
      associated with the host range of the virus strains, suggesting that glycan
      diversity contributes to lagoviruses' host range.

PMID- 29187538
TI  - The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection.
AB  - UL20, an essential herpes simplex virus 1 (HSV-1) protein, is involved in
      cytoplasmic envelopment of virions and virus egress. We reported recently that
      UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3
      (ZDHHC3) gene (also known as Golgi-specific DHHC zinc finger protein [GODZ]).
      Here, we show for the first time that HSV-1 replication is compromised in murine
      embryonic fibroblasts (MEFs) isolated from GODZ-/- mice. The absence of GODZ
      resulted in blocking palmitoylation of UL20 and altered localization and
      expression of UL20 and glycoprotein K (gK); the expression of gB and gC; and the
      localization and expression of tegument and capsid proteins within HSV-1-infected
      MEFs. Electron microscopy revealed that the absence of GODZ limited the
      maturation of virions at multiple steps and affected the localization of virus
      and endoplasmic reticulum morphology. Virus replication in the eyes of ocularly
      HSV-1-infected GODZ-/- mice was significantly lower than in HSV-1-infected wild
      type (WT) mice. The levels of UL20, gK, and gB transcripts in the corneas of HSV
      1-infected GODZ-/- mice on day 5 postinfection were markedly lower than in WT
      mice, whereas only UL20 transcripts were reduced in trigeminal ganglia (TG). In
      addition, HSV-1-infected GODZ-/- mice showed notably lower levels of corneal
      scarring, and HSV-1 latency reactivation was also reduced. Thus, normal HSV-1
      infectivity and viral pathogenesis are critically dependent on GODZ-mediated
      palmitoylation of viral UL20.IMPORTANCE HSV-1 infection is widespread. Ocular
      infection can cause corneal blindness; however, approximately 70 to 90% of
      American adults exposed to the virus show no clinical symptoms. In this study, we
      show for the first time that the absence of a zinc finger protein called GODZ
      affects primary and latent infection, as well as reactivation, in ocularly
      infected mice. The reduced virus infectivity is due to the absence of the GODZ
      interaction with HSV-1 UL20. These results strongly suggest that binding of UL20
      to GODZ promotes virus infectivity in vitro and viral pathogenesis in vivo.

PMID- 29187539
TI  - Prasinovirus Attack of Ostreococcus Is Furtive by Day but Savage by Night.
AB  - Prasinoviruses are large DNA viruses that infect diverse genera of green
      microalgae worldwide in aquatic ecosystems, but molecular knowledge of their life
      cycles is lacking. Several complete genomes of both these viruses and their
      marine algal hosts are now available and have been used to show the pervasive
      presence of these species in microbial metagenomes. We have analyzed the life
      cycle of Ostreococcus tauri virus 5 (OtV5), a lytic virus, using transcriptome
      sequencing (RNA-Seq) from 12 time points of healthy or infected Ostreococcus
      tauri cells over a day/night cycle in culture. In the day, viral gene
      transcription remained low while host nitrogen metabolism gene transcription was
      initially strongly repressed for two successive time points before being induced
      for 8 h, but during the night, viral transcription increased steeply while host
      nitrogen metabolism genes were repressed and many host functions that are
      normally reduced in the dark appeared to be compensated either by genes expressed
      from the virus or by increased expression of a subset of 4.4% of the host's
      genes. Some host cells underwent lysis progressively during the night, but a
      larger proportion were lysed the following morning. Our data suggest that the
      life cycles of algal viruses mirror the diurnal rhythms of their hosts.IMPORTANCE
      Prasinoviruses are common in marine environments, and although several complete
      genomes of these viruses and their hosts have been characterized, little is known
      about their life cycles. Here we analyze in detail the transcriptional changes
      occurring over a 27-h-long experiment in a natural diurnal rhythm, in which the
      growth of host cells is to some extent synchronized, so that host DNA replication
      occurs late in the day or early in the night and cell division occurs during the
      night. Surprisingly, viral transcription remains quiescent over the daytime, when
      the most energy (from light) is available, but during the night viral
      transcription activates, accompanied by expression of a few host genes that are
      probably required by the virus. Although our experiment was accomplished in the
      lab, cyclical changes have been documented in host transcription in the ocean.
      Our observations may thus be relevant for eukaryotic phytoplankton in natural
      environments.

PMID- 29187540
TI  - General Model for Retroviral Capsid Pattern Recognition by TRIM5 Proteins.
AB  - Restriction factors are intrinsic cellular defense proteins that have evolved to
      block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5
      proteins, which recognize the viral capsid shell that surrounds, organizes, and
      protects the viral genome. TRIM5alpha uses a SPRY domain to bind capsids with low
      intrinsic affinity (KD of >1 mM) and therefore requires higher-order assembly
      into a hexagonal lattice to generate sufficient avidity for productive capsid
      recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a
      cyclophilin A domain, which has a well-defined binding site and higher affinity
      (KD of ~10 MUM) for isolated capsid subunits. Therefore, it has been argued that
      TRIMCyp proteins have dispensed with the need for higher-order assembly to
      function as antiviral factors. Here, we show that, consistent with its high
      degree of sequence similarity with TRIM5alpha, the TRIMCyp B-box 2 domain shares
      the same ability to self-associate and facilitate assembly of a TRIMCyp hexagonal
      lattice that can wrap about the HIV-1 capsid. We also show that under stringent
      experimental conditions, TRIMCyp-mediated restriction of HIV-1 is indeed
      dependent on higher-order assembly. Both forms of TRIM5 therefore use the same
      mechanism of avidity-driven capsid pattern recognition.IMPORTANCE Rhesus macaques
      and owl monkeys are highly resistant to HIV-1 infection due to the activity of
      TRIM5 restriction factors. The rhesus macaque TRIM5alpha protein blocks HIV-1
      through a mechanism that requires self-assembly of a hexagonal TRIM5alpha lattice
      around the invading viral core. Lattice assembly amplifies very weak interactions
      between the TRIM5alpha SPRY domain and the HIV-1 capsid. Assembly also promotes
      dimerization of the TRIM5alpha RING E3 ligase domain, resulting in synthesis of
      polyubiquitin chains that mediate downstream steps of restriction. In contrast to
      rhesus TRIM5alpha, the owl monkey TRIM5 homolog, TRIMCyp, binds isolated HIV-1 CA
      subunits much more tightly through its cyclophilin A domain and therefore was
      thought to act independently of higher-order assembly. Here, we show that TRIMCyp
      shares the assembly properties of TRIM5alpha and that both forms of TRIM5 use the
      same mechanism of hexagonal lattice formation to promote viral recognition and
      restriction.

PMID- 29187542
TI  - Type III Interferon Restriction by Porcine Epidemic Diarrhea Virus and the Role
      of Viral Protein nsp1 in IRF1 Signaling.
AB  - Type III interferons (IFNs) play a vital role in maintaining the antiviral state
      of the mucosal epithelial surface in the gut, and in turn, enteric viruses may
      have evolved to evade the type III IFN responses during infection. To study the
      possible immune evasion of the type III IFN response by porcine epidemic diarrhea
      virus (PEDV), a line of porcine intestinal epithelial cells was developed as a
      cell model for PEDV replication. IFN-lambda1 and IFN-lambda3 inhibited PEDV
      replication, indicating the anti-PEDV activity of type III IFNs. Of the 21 PEDV
      proteins, nsp1, nsp3, nsp5, nsp8, nsp14, nsp15, nsp16, open reading frame 3
      (ORF3), E, M, and N were found to suppress type III IFN activities, and IRF1
      (interferon regulatory factor 1) signaling mediated the suppression. PEDV
      specifically inhibited IRF1 nuclear translocation. The peroxisome is the innate
      antiviral signaling platform for the activation of IRF1-mediated IFN-lambda
      production, and the numbers of peroxisomes were found to be decreased in PEDV
      infected cells. PEDV nsp1 blocked the nuclear translocation of IRF1 and reduced
      the number of peroxisomes to suppress IRF1-mediated type III IFNs. Mutational
      studies showed that the conserved residues of nsp1 were crucial for IRF1-mediated
      IFN-lambda suppression. Our study for the first time provides evidence that the
      porcine enteric virus PEDV downregulates and evades IRF1-mediated type III IFN
      responses by reducing the number of peroxisomes.IMPORTANCE Porcine epidemic
      diarrhea virus (PEDV) is a highly contagious enteric coronavirus that emerged in
      swine in the United States and has caused severe economic losses. PEDV targets
      intestinal epithelial cells in the gut, and intestinal epithelial cells
      selectively induce and respond to the production of type III interferons (IFNs).
      However, little is known about the modulation of the type III IFN response by
      PEDV in intestinal epithelial cells. In this study, we established a porcine
      intestinal epithelial cell model for PEDV replication. We found that PEDV
      inhibited IRF1-mediated type III IFN production by decreasing the number of
      peroxisomes in porcine intestinal epithelial cells. We also demonstrated that the
      conserved residues in the PEDV nsp1 protein were crucial for IFN suppression.
      This study for the first time shows PEDV evasion of the type III IFN response in
      intestinal epithelial cells, and it provides valuable information on host cell
      virus interactions not only for PEDV but also for other enteric viral infections
      in swine.

PMID- 29187541
TI  - Exosomes Mediate Intercellular Transmission of Porcine Reproductive and
      Respiratory Syndrome Virus.
AB  - Exosomes are small membrane-enclosed vesicles produced by various cells and
      actively released into the extracellular space. They participate in intercellular
      communication and transfer of biologically active proteins, lipids, and nucleic
      acids. Accumulating evidence suggests that exosomes derived from cells infected
      by some viruses selectively encapsulate viral proteins, genetic materials, or
      even virions to mediate cell-to-cell communication and/or virus transmission.
      Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus
      that has been devastating the global swine industry since the late 1980s. Recent
      studies have shown that major proteins secreted from PRRSV-infected cells are
      exosomal proteins and that the serum-derived exosomes from PRRSV-infected pigs
      contain viral proteins. However, the role of exosomes in PRRSV infection remains
      unclear. In this study, purified exosomes isolated from PRRSV-infected cells were
      shown with reverse transcription-PCR and mass spectrometry to contain viral
      genomic RNA and partial viral proteins. Furthermore, exosomes from PRRSV-infected
      cells established productive infection in both PRRSV-susceptible and 
      nonsusceptible cells. More importantly, exosome-mediated infection was not
      completely blocked by PRRSV-specific neutralizing antibodies. In summary, this
      study demonstrated that exosomes can mediate PRRSV transmission and are even
      resistant to antibody neutralization, identifying a potential immune evasion
      mechanism utilized by PRRSV.IMPORTANCE Exosomes have recently been characterized
      as bioactive vesicles that function to promote intercellular communication. The
      exosomes from virally infected cells containing altered compositions confer
      numerous novel functionalities. A study of the secretome of cells infected with
      PRRSV indicated that the exosomal pathway is strongly activated by PRRSV
      infection. Here, we demonstrate that PRRSV can utilize host exosomes to infect
      naive healthy cells. Furthermore, exosome-mediated viral transmission is largely
      resistant to PRRSV-specific neutralizing antibodies. Our study provides novel
      insights into an alternative mechanism of PRRSV transmission that can compromise
      the host's anti-PRRSV immune response.

PMID- 29187543
TI  - A proteomic survey of Junin virus interactions with human proteins reveals host
      factors required for arenavirus replication.
AB  - Arenaviruses are negative-strand, enveloped RNA viruses that cause significant
      human disease. In particular, Junin mammarenvirus (JUNV) is the etiologic agent
      of Argentine hemorrhagic fever. At present, little is known about the cellular
      proteins that the arenavirus matrix protein (Z) hijacks to accomplish its various
      functions, including driving the process of virus release. Further, there is a
      little knowledge regarding host proteins incorporated into arenavirus particles
      and their importance for virion function. To address these deficiencies, we used
      mass spectrometry to identify human proteins that (i) interact with the JUNV
      matrix protein inside of cells or within virus-like particles (VLPs) and/or (ii)
      are incorporated into bona fide JUNV strain Candid #1 particles. Bioinformatic
      analyses revealed that multiple classes of human proteins were overrepresented in
      the datasets, including ribosomal proteins, Ras superfamily proteins, and
      endosomal sorting complex required for transport (ESCRT) proteins. Several of
      these proteins were required for the propagation of JUNV (ARF1, ATP6V0D1 and
      PRDX3), lymphocytic choriomeningitis mammarenavirus (LCMV) (Rab5c), or both
      viruses (ATP5B, IMPDH2). Further, we show that release of infectious JUNV
      particles, but not LCMV particles, requires a functional ESCRT pathway and that
      ATP5B and IMPDH2 are required for JUNV budding. In summary, we have provided a
      large-scale map of host machinery that associates with JUNV and identified key
      human proteins required for its propagation. This dataset provides a resource for
      the field to guide antiviral target discovery and to better understand the
      biology of the arenavirus matrix protein and the importance of host proteins for
      virion function.IMPORTANCE Arenaviruses are deadly human pathogens for which
      there are no United States Food and Drug Administration-approved vaccines and
      only limited treatment options. Little is known about the host proteins that are
      incorporated into arenavirus particles or that associate with its multifunctional
      matrix protein. Using Junin mammarenavirus (JUNV), the causative agent of
      Argentine hemorrhagic fever, as a model organism, we mapped the human proteins
      that are incorporated into JUNV particles or that associate with the JUNV matrix
      protein. Functional analysis revealed host machinery that is required for JUNV
      propagation, including the cellular ESCRT pathway. This study improves our
      understanding of critical arenavirus-host interactions and provides a dataset
      that will guide future studies to better understand arenavirus pathogenesis and
      identify novel host proteins that can be therapeutically targeted.

PMID- 29187544
TI  - Genetically Intact but Functionally Impaired HIV-1 Env Glycoproteins in the T
      Cell Reservoir.
AB  - HIV-infected subjects under antiretroviral treatment (ART) harbor a persistent
      viral reservoir in resting CD4+ T cells, which accounts for the resurgence of HIV
      replication after ART interruption. A large majority of HIV reservoir genomes are
      genetically defective, but even among intact proviruses few seem able to generate
      infectious virus. To understand this phenomenon, we examined the function and
      expression of HIV envelope glycoproteins reactivated from the reservoir of four
      HIV-infected subjects under suppressive ART. We studied full-length genetically
      intact env sequences from both replicative viruses and cell-associated mRNAs. We
      found that these Env proteins varied extensively in fusogenicity and infectivity,
      with strongest functional defects found in Envs from cell-associated mRNAs. Env
      functional impairments were essentially explained by defects in Env protein
      expression. Our results support the idea that defects in HIV Env expression,
      preventing cytopathic or immune HIV clearance, contribute to the persistence of
      the HIV T-cell reservoir in vivoIMPORTANCE In most individuals, evolution of HIV
      infection is efficiently controlled on the long-term by combination antiviral
      therapies. These treatments, however, fail to eradicate HIV from the infected
      subjects, a failure that results both in resurgence of virus replication and in
      resumption of HIV pathogenicity when the treatment is stopped. HIV resurgence, in
      these instances, is widely assumed to emerge from a reservoir of silent virus
      integrated in the genomes of a small number of T lymphocytes. The silent HIV
      reservoir is mostly composed of heavily deleted or mutated HIV DNA. Moreover,
      among the seemingly intact remaining HIV, only very few are actually able to
      efficiently propagate in tissue culture. In this study, we find that intact HIV
      in the reservoir often carry strong defects in their capacity to promote fusion
      to neighboring cells and infection of target cells, a defect related to the
      function and expression of the HIV envelope glycoprotein. Impaired envelope
      glycoprotein expression and function could explain why cells harboring these
      viruses tend to remain undetected and unharmed in the reservoir.

PMID- 29187547
TI  - Effect of sensory attenuation on cortical movement-related oscillations.
AB  - This study examined the impact of induced sensory deficits on cortical, movement
      related oscillations measured using electroencephalography (EEG). We hypothesized
      that EEG patterns in healthy subjects with induced sensory reduction would be
      comparable to EEG found after chronic loss of sensory feedback. EEG signals from
      64 scalp locations were measured from 10 healthy subjects. Participants
      dorsiflexed their ankle after prolonged vibration of the tibialis anterior (TA).
      Beta band time frequency decompositions were calculated using wavelets and
      compared across conditions. Changes in patterns of movement-related brain
      activity were observed following attenuation of sensory feedback. A significant
      decrease in beta power of event-related synchronization was associated with
      simple ankle dorsiflexion after prolonged vibration of the TA. Attenuation of
      sensory feedback in young, healthy subjects led to a corresponding decrease in
      beta band synchronization. This temporary change in beta oscillations suggests
      that these modulations are a mechanism for sensorimotor integration. The loss of
      sensory feedback found in spinal cord injury patients contributes to changes in
      EEG signals underlying motor commands. Similar alterations in cortical signals in
      healthy subjects with reduced sensory feedback implies these changes reflect
      normal sensorimotor integration after reduced sensory input rather than brain
      plasticity. NEW & NOTEWORTHY Transient attenuation of sensory afferents in young,
      healthy adults led to similar changes in brain activity found previously in
      volunteers with incomplete spinal cord injury. Beta band power associated with
      ankle movement in these controls was attenuated after prolonged vibration of the
      tibialis anterior. Evoked potential measurements suggest that prolonged vibration
      reduces phasing across trials as the mechanism behind this attenuation of
      cortical activity.

PMID- 29187546
TI  - Pathogenesis, humoral immune responses and transmission between co-housed animals
      in a ferret model of human RSV infection.
AB  - Small animal models have been used to obtain many insights regarding the
      pathogenesis and immune responses induced following infection with human
      respiratory syncytial virus (hRSV). Amongst those described to date, infections
      in cotton rats, mice, guinea pigs, chinchillas and Syrian hamsters with hRSV
      strains Long and/or A2 have been well characterised, although clinical isolates
      have also been examined. Ferrets are also susceptible to hRSV infection but the
      pathogenesis and immune responses elicited following infection have not been well
      characterised. Herein, we describe the infection of adult ferrets with hRSV Long
      or A2 via the intranasal route and characterised virus replication, as well as
      cytokine induction, in the upper and lower airways. Virus replication and
      cytokine induction during the acute phase of infection (days 0-15 post-infection)
      were similar between the two strains and both elicited high levels of F
      glycoprotein-specific binding and neutralising antibodies following virus
      clearance (days 16-22 post-infection). Importantly, we demonstrate transmission
      from experimentally infected donor ferrets to co-housed naive recipients and have
      characterised virus replication and cytokine induction in the upper airways of
      infected contact animals. Together, these studies provide a direct comparison of
      the pathogenesis of hRSV Long and A2 in ferrets and highlight the potential of
      this animal model to study serological responses and examine interventions that
      limit transmission of hRSV.IMPORTANCE Ferrets have been widely used to study
      pathogenesis, immunity and transmission following human influenza virus
      infections, however far less is known regarding the utility of the ferret model
      to study hRSV infections. Following intranasal (IN) infection of adult ferrets
      with the well characterised Long or A2 strains of hRSV, we report virus
      replication and cytokine induction in the upper and lower airways, as well as the
      development of virus-specific humoral responses. Importantly, we demonstrate
      transmission of hRSV from experimentally infected donor ferrets to co-housed
      naive recipients. Together, these findings significantly enhance our
      understanding of the utility of the ferret as a small animal model to investigate
      aspects of hRSV pathogenesis and immunity.

PMID- 29187545
TI  - Novel Insect-Specific Eilat Virus-Based Chimeric Vaccine Candidates Provide
      Durable, Mono- and Multivalent, Single-Dose Protection against Lethal Alphavirus
      Challenge.
AB  - Most alphaviruses are mosquito borne and exhibit a broad host range, infecting
      many different vertebrates, including birds, rodents, equids, humans, and
      nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat
      virus (EILV), was described with an inability to infect vertebrate cells based on
      defective attachment and/or entry, as well as a lack of genomic RNA replication.
      We investigated the utilization of EILV recombinant technology as a vaccine
      platform against eastern (EEEV) and Venezuelan equine encephalitis viruses
      (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras
      containing structural proteins of EEEV or VEEV were engineered and successfully
      rescued in Aedes albopictus cells. Cryo-electron microscopy reconstructions at 8
      and 11 A of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein
      spike structures similar to those of VEEV-TC83 and other alphaviruses. The
      chimeras were unable to replicate in vertebrate cell lines or in brains of
      newborn mice when injected intracranially. Histopathologic examinations of the
      brain tissues showed no evidence of pathological lesions and were
      indistinguishable from those of mock-infected animals. A single-dose immunization
      of either monovalent or multivalent EILV chimera(s) generated neutralizing
      antibody responses and protected animals against lethal challenge 70 days later.
      Lastly, a single dose of monovalent EILV chimeras generated protective responses
      as early as day 1 postvaccination and partial or complete protection by day 6.
      These data demonstrate the safety, immunogenicity, and efficacy of novel insect
      specific EILV-based chimeras as potential EEEV and VEEV vaccines.IMPORTANCE
      Mostly in the last decade, insect-specific viruses have been discovered in
      several arbovirus families. However, most of these viruses are not well studied
      and largely have been ignored. We explored the use of the mosquito-specific
      alphavirus EILV as an alphavirus vaccine platform in well-established disease
      models for eastern (EEE) and Venezuelan equine encephalitis (VEE). EILV-based
      chimeras replicated to high titers in a mosquito cell line yet retained their
      host range restriction in vertebrates both in vitro and in vivo In addition, the
      chimeras generated immune responses that were higher than those of other human
      and/or equine vaccines. These findings indicate the feasibility of producing a
      safe, efficacious, mono- or multivalent vaccine against the encephalitic
      alphaviruses VEEV and EEEV. Lastly, these data demonstrate how host-restricted,
      insect-specific viruses can be engineered to develop vaccines against related
      pathogenic arboviruses that cause severe disease in humans and domesticated
      animals.

PMID- 29187548
TI  - Estimating properties of the fast and slow adaptive processes during sensorimotor
      adaptation.
AB  - Experience of a prediction error recruits multiple motor learning processes, some
      that learn strongly from error but have weak retention and some that learn weakly
      from error but exhibit strong retention. These processes are not generally
      observable but are inferred from their collective influence on behavior. Is there
      a robust way to uncover the hidden processes? A standard approach is to consider
      a state space model where the hidden states change following experience of error
      and then fit the model to the measured data by minimizing the squared error
      between measurement and model prediction. We found that this least-squares
      algorithm (LMSE) often yielded unrealistic predictions about the hidden states,
      possibly because of its neglect of the stochastic nature of error-based learning.
      We found that behavioral data during adaptation was better explained by a system
      in which both error-based learning and movement production were stochastic
      processes. To uncover the hidden states of learning, we developed a generalized
      expectation maximization (EM) algorithm. In simulation, we found that although
      LMSE tracked the measured data marginally better than EM, EM was far more
      accurate in unmasking the time courses and properties of the hidden states of
      learning. In a power analysis designed to measure the effect of an intervention
      on sensorimotor learning, EM significantly reduced the number of subjects that
      were required for effective hypothesis testing. In summary, we developed a new
      approach for analysis of data in sensorimotor experiments. The new algorithm
      improved the ability to uncover the multiple processes that contribute to
      learning from error. NEW & NOTEWORTHY Motor learning is supported by multiple
      adaptive processes, each with distinct error sensitivity and forgetting rates. We
      developed a generalized expectation maximization algorithm that uncovers these
      hidden processes in the context of modern sensorimotor learning experiments that
      include error-clamp trials and set breaks. The resulting toolbox may improve the
      ability to identify the properties of these hidden processes and reduce the
      number of subjects needed to test the effectiveness of interventions on
      sensorimotor learning.

PMID- 29187549
TI  - Quantitative input-output relationships between human soleus muscle spindle
      afferents and motoneurons.
AB  - A method is described that, for the first time, allows instantaneous estimation
      of the Ia fiber input to human soleus motoneurons following electrical
      stimulation of the tibial nerve. The basis of the method is to determine the
      thresholds of the most and least excitable 1a fibers to electrical stimulation,
      and to treat the intervening thresholds as having a normal distribution about the
      mean; the validity of this approach is discussed. It was found that, for the same
      Ia fiber input, the percentage of soleus motoneurons contributing to the H
      (Hoffmann)-reflex differed considerably among subjects; when the results were
      pooled, however, there was an approximately linear relationship between Ia input
      and motoneuron output. Weak extension of the great toe diminished the soleus
      motoneuron reflex discharge in all but 2 of 16 subjects; the results for weak
      ankle plantarflexion were less consistent, but overall, there was a reduction in
      soleus motoneuron output also. The methodology should provide new insights into
      disorders of movement and tone, especially as it permits estimates of motoneuron
      depolarization to be made. NEW & NOTEWORTHY Assuming a normal distribution of Ia
      fiber thresholds to electrical stimulation and using the H-reflex, we determined
      for the first time an Ia input-alpha-motoneuron output relationship for the human
      soleus muscle. The relationship varies greatly among subjects but, overall, is
      approximately linear. Minimal contraction of a toe muscle alters the relationship
      dramatically, probably due to presynaptic inhibition of Ia fibers. Drawing on the
      literature, we can calculate changes in alpha-motoneuron membrane potential.

PMID- 29187550
TI  - Quantitative relations between BOLD responses, cortical energetics, and impulse
      firing.
AB  - The blood oxygen level-dependent (BOLD) functional magnetic resonance imaging
      signal arises as a consequence of changes in blood flow and oxygen usage that in
      turn are modulated by changes in neural activity. Much attention has been given
      to both theoretical and experimental aspects of the energetics but not to the
      neural activity. Here we identify the best energetic theory for the steady-state
      BOLD signal on the basis of correct predictions of experimental observations.
      This theory is then used, together with the recently determined relationship
      between energetics and neural activity, to predict how the BOLD signal changes
      with activity. Unlike existing treatments, this new theory incorporates a nonzero
      baseline activity in a completely consistent way and is thus able to account for
      both sustained positive and negative BOLD signals. We also show that the increase
      in BOLD signal for a given increase in activity is significantly smaller the
      larger the baseline activity, as is experimentally observed. Furthermore, the
      decline of the positive BOLD signal arising from deeper cortical laminae in
      response to an increase in neural firing is shown to arise as a consequence of
      the larger baseline activity in deeper laminae. Finally, we provide quantitative
      relations integrating BOLD responses, energetics, and impulse firing, which among
      other predictions give the same results as existing theories when the baseline
      activity is zero. NEW & NOTEWORTHY We use a recently established relation between
      energetics and neural activity to give a quantitative account of BOLD dependence
      on neural activity. The incorporation of a nonzero baseline neural activity
      accounts for positive and negative BOLD signals, shows that changes in neural
      activity give BOLD changes that are smaller the larger the baseline, and provides
      a basis for the observed inverse relation between BOLD responses and the depth of
      cortical laminae giving rise to them.

PMID- 29187552
TI  - Implantable computer-controlled adaptive multielectrode positioning system.
AB  - Acute neuronal recordings performed with metal microelectrodes in nonhuman
      primates allow investigating the neural substrate of complex cognitive behaviors.
      Yet the daily reinsertion and positioning of the electrodes prevents recording
      from many neurons simultaneously, limiting the suitability of these types of
      recordings for brain-computer interface applications or for large-scale
      population statistical methods on a trial-by-trial basis. In contrast,
      chronically implanted multielectrode arrays offer the opportunity to record from
      many neurons simultaneously, but immovable electrodes prevent optimization of the
      signal during and after implantation and cause the tissue response to
      progressively impair the transduced signal quality, thereby limiting the number
      of different neurons that can be recorded over the lifetime of the implant.
      Semichronically implanted matrices of electrodes, instead, allow individually
      movable electrodes in depth and achieve higher channel count compared with acute
      methods, hence partially overcoming these limitations. Existing semichronic
      systems with higher channel count lack computerized control of electrode
      movements, leading to limited user-friendliness and uncertainty in depth
      positioning. Here we demonstrate a chronically implantable adaptive
      multielectrode positioning system with detachable drive for computerized depth
      adjustment of individual electrodes over several millimeters. This semichronic 16
      channel system is designed to optimize the simultaneous yield of units in an
      extended period following implantation since the electrodes can be independently
      depth adjusted with minimal effort and their signal quality continuously
      assessed. Importantly, the electrode array is designed to remain within a chronic
      recording chamber for a prolonged time or can be used for acute recordings with
      high signal-to-noise ratio in the cerebral cortex of nonhuman primates. NEW &
      NOTEWORTHY We present a 16-channel motorized, semichronic multielectrode array
      with individually depth-adjustable electrodes to record in the cerebral cortex of
      nonhuman primates. Compared with fixed-geometry arrays, this system allows
      repeated reestablishing of single neuron isolation. Compared with manually
      adjustable arrays it benefits from computer-controlled positioning. Compared with
      motorized semichronic systems it allows higher channel counts due to a robotic
      single actuator approach. Overall the system is designed to optimize the
      simultaneous yield of units over the course of implantation.

PMID- 29187551
TI  - Model of a bilateral Brown-type central pattern generator for symmetric and
      asymmetric locomotion.
AB  - The coordinated activity of muscles is produced in part by spinal rhythmogenic
      neural circuits, termed central pattern generators (CPGs). A classical CPG model
      is a system of coupled oscillators that transform locomotor drive into
      coordinated and gait-specific patterns of muscle recruitment. The network
      properties of this conceptual model can be simulated by a system of ordinary
      differential equations with a physiologically inspired coupling locus of
      interactions capturing the timing relationship for bilateral coordination of
      limbs in locomotion. Whereas most similar models are solved numerically, it is
      intriguing to have a full analytical description of this plausible CPG
      architecture to illuminate the functionality within this structure and to expand
      it to include steering control. Here, we provided a closed-form analytical
      solution contrasted against the previous numerical method. The evaluation time of
      the analytical solution was decreased by an order of magnitude when compared with
      the numerical approach (relative errors, <0.01%). The analytical solution tested
      and supported the previous finding that the input to the model can be expressed
      in units of the desired limb locomotor speed. Furthermore, we performed
      parametric sensitivity analysis in the context of controlling steering and
      documented two possible mechanisms associated with either an external drive or
      intrinsic CPG parameters. The results identify specific propriospinal pathways
      that may be associated with adaptations within the CPG structure. The model
      offered several network configurations that may generate the same behavioral
      outcomes. NEW & NOTEWORTHY Using a simple process of leaky integration, we
      developed an analytical solution to a robust model of spinal pattern generation.
      We analyzed the ability of this neural element to exert locomotor control of the
      signal associated with limb speeds and tested the ability of this simple
      structure to embed steering control using the velocity signal in the model's
      inputs or within the internal connectivity of its elements.

PMID- 29187553
TI  - Ih interacts with somato-dendritic structure to determine frequency response to
      weak alternating electric field stimulation.
AB  - Transcranial current stimulation (tCS) modulates brain dynamics using weak
      electric fields. Given the pathological changes in brain network oscillations in
      neurological and psychiatric illnesses, using alternating electric field
      waveforms that engage rhythmic activity has been proposed as a targeted, network
      level treatment approach. Previous studies have investigated the effects of
      electric fields at the neuronal level. However, the biophysical basis of the
      cellular response to electric fields has remained limited. Here, we characterized
      the frequency-dependent response of different compartments in a layer V pyramidal
      neuron to exogenous electric fields to dissect the relative contributions of
      voltage-gated ion channels and neuronal morphology. Hyperpolarization-activated
      cation current (Ih) in the distal dendrites was the primary ionic mechanism
      shaping the model's response to electric field stimulation and caused
      subthreshold resonance in the tuft at 20 +/- 4 Hz. In contrast, subthreshold Ih
      mediated resonance in response to local sinusoidal current injection was present
      in all model compartments at 11 +/- 2 Hz. The frequencies of both resonance
      responses were modulated by Ih conductance density. We found that the difference
      in resonance frequency between the two stimulation types can be explained by the
      fact that exogenous electric fields simultaneously polarize the membrane
      potentials at the distal ends of the neuron (relative to field direction) in
      opposite directions. Our results highlight the role of Ih in shaping the cellular
      response to electric field stimulation and suggest that the common model of tCS
      as a weak somatic current injection fails to capture the cellular effects of
      electric field stimulation. NEW & NOTEWORTHY Modulation of cortical oscillation
      by brain stimulation serves as a tool to understand the causal role of network
      oscillations in behavior and is a potential treatment modality that engages
      impaired network oscillations in disorders of the central nervous system. To
      develop targeted stimulation paradigms, cellular-level effects must be
      understood. We demonstrate that hyperpolarization-activated cation current (Ih)
      and cell morphology cooperatively shape the response to applied alternating
      electric fields.

PMID- 29187554
TI  - Clustering of heading selectivity and perception-related activity in the ventral
      intraparietal area.
AB  - The ventral intraparietal area (VIP) of the macaque brain is a multimodal
      cortical region, with many cells tuned to both optic flow and vestibular stimuli.
      Responses of many VIP neurons also show robust correlations with perceptual
      judgments during a fine heading discrimination task. Previous studies have shown
      that heading tuning based on optic flow is represented in a clustered fashion in
      VIP. However, it is unknown whether vestibular self-motion selectivity is
      clustered in VIP. Moreover, it is not known whether stimulus- and choice-related
      signals in VIP show clustering in the context of a heading discrimination task.
      To address these issues, we compared the response characteristics of isolated
      single units (SUs) with those of the undifferentiated multiunit (MU) activity
      corresponding to several neighboring neurons recorded from the same
      microelectrode. We find that MU activity typically shows selectivity similar to
      that of simultaneously recorded SUs, for both the vestibular and visual stimulus
      conditions. In addition, the choice-related activity of MU signals, as quantified
      using choice probabilities, is correlated with the choice-related activity of
      SUs. Overall, these findings suggest that both sensory and choice-related signals
      regarding self-motion are clustered in VIP. NEW & NOTEWORTHY We demonstrate, for
      the first time, that the vestibular tuning of ventral intraparietal area (VIP)
      neurons in response to both translational and rotational motion is clustered. In
      addition, heading discriminability and choice-related activity are also weakly
      clustered in VIP.

PMID- 29187555
TI  - Complementary metrics of human auditory nerve function derived from compound
      action potentials.
AB  - Declines in auditory nerve (AN) function contribute to suprathreshold auditory
      processing and communication deficits in individuals with normal hearing, hearing
      loss, hyperacusis, and tinnitus. Procedures to characterize AN loss or
      dysfunction in humans are limited. We report several novel complementary metrics
      using the compound action potential (CAP), a direct measure of summated AN
      activity. Together, these metrics may be used to characterize AN function
      noninvasively in humans. We examined how these metrics change with stimulus
      intensity and interpreted these changes within a framework of known physiological
      properties of the basilar membrane and AN. Our results reveal how neural
      synchrony and the recruitment of AN fibers with longer first-spike latencies
      likely contribute to the CAP, affect auditory processing, and differ with noise
      exposure history in younger adults with normal pure-tone thresholds. Moving
      forward, this new battery of metrics provides a crucial step toward new
      diagnostics of AN function in humans. NEW & NOTEWORTHY Loss or inactivity of
      auditory nerve (AN) fibers is thought to contribute to suprathreshold auditory
      processing deficits, but evidence-based methods to assess these effects are not
      available. We describe several novel metrics that together may be used to
      quantify neural synchrony and characterize AN function in humans.

PMID- 29187557
TI  - The assessment of neurovascular coupling with the Addenbrooke's Cognitive
      Examination: a functional transcranial Doppler ultrasonographic study.
AB  - Cerebrovascular dysfunction occurs early in dementia and can be identified by
      transcranial Doppler ultrasonography (TCD). Few studies have examined cerebral
      blood flow velocity (CBFv) responses to a detailed cognitive battery. This study
      aimed to characterize all CBFv responses, and the effect of hemispheric
      dominance, to the Addenbrooke's Cognitive Examination (ACE-III) in healthy
      volunteers. Forty volunteers underwent continuous bilateral TCD, beat-to-beat
      blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal
      CO2 (ETCO2; capnography) monitoring. After a 5-min baseline period, all tasks
      from the ACE-III were performed in 3 sections (A: attention, fluency, memory; B:
      language; C: visuospatial, memory). Data are population mean normalized
      percentage (PM%) change from a 20-s baseline period before task initiation. Forty
      bilateral data sets were obtained (27 women, 37 right-hand dominant). All
      paradigms produced a sharp increase in CBFv in both dominant (PM% range: 3.29 to
      9.70%) and nondominant (PM% range: 4.34 to 11.63%) hemispheres at task
      initiation, with associated increases in MAP (PM% range: 3.06 to 16.04%). ETCO2
      did not differ significantly at task initiation (PM% range: -1.1 to 2.4%, P >
      0.05). HR differed significantly across A and C tasks at initiation (PM% range: 
      1.1 to 2.4%, P < 0.05), but not B tasks. In conclusion, all tasks resulted in
      increases in CBFv, differing significantly between paradigms. These results
      require further investigation in a cognitively impaired population. NEW &
      NOTEWORTHY This study is the first to provide a normative data set of cerebral
      blood flow velocity (CBFv) responses to a complete cognitive assessment
      (Addenbrooke's Cognitive Examination, ACE-III) in a large sample ( n = 40) of
      healthy volunteers. All tasks produced peak and sustained increases in CBFv to
      different extents. The ACE-III is a feasible tool to assess neurovascular
      coupling with transcranial Doppler ultrasonography. These data can be used to
      inform the most appropriate cognitive task to elicit CBFv responses for future
      studies.

PMID- 29187558
TI  - Modeling spatial navigation in the presence of dynamic obstacles: a differential
      games approach.
AB  - Obstacle circumvention strategies can be shaped by the dynamic interaction of an
      individual (evader) and an obstacle (pursuer). We have developed a mathematical
      model with predictive and emergent components, using experimental data from seven
      healthy young adults walking toward a target while avoiding collision with a
      stationary or moving obstacle (approaching head-on, or diagonally 30 degrees 
      left or right) in a virtual environment. Two linear properties from the
      predictive component enable the evader to predict the minimum distance between
      itself and the obstacle at all times, including the future intersection of
      trajectories. The emergent component uses the classical differential games model
      to solve for an optimal circumvention while reaching the target, wherein the
      locomotor strategy is influenced by the obstacle, target, and the evader
      velocity. Both model components were fitted to a different set of experimental
      data obtained from five poststroke and healthy participants to derive the minimum
      predicted distance (predictive component) and obstacle influence dimensions
      (emergent component) during circumvention. Minimum predicted distance between
      evader and pursuer was kept constant when the evader was closest to the obstacle
      in all participants. Obstacle influence dimensions varied depending on obstacle
      approach condition and preferred side of circumvention, reflecting differences in
      locomotor strategies between poststroke and healthy individuals. Additionally,
      important associations between model outputs and observed experimental outcomes
      were found. The model, supported by experimental data, suggests that both
      predictive and emergent processes can shape obstacle circumvention strategies in
      healthy and poststroke individuals. NEW & NOTEWORTHY Obstacle circumvention
      during goal-directed locomotion is modeled with a new mathematical approach
      comprising both predictive and emergent elements. The major novelty is using
      differential games solutions to illustrate the dynamic interactions between the
      individual as an evader and the approaching obstacle as a pursuer. The model is
      supported by experimental evidence that explains the behavior along the continuum
      of locomotor adaptation displayed by healthy subjects and individuals with
      stroke.

PMID- 29187556
TI  - Time course of functional recovery during the first 3 mo after surgical
      transection and repair of nerves to the feline soleus and lateral gastrocnemius
      muscles.
AB  - Locomotion outcomes after peripheral nerve injury and repair in cats have been
      described in the literature for the period immediately following the injury
      (muscle denervation period) and then again for an ensuing period of long-term
      recovery (at 3 mo and longer) resulting in muscle self-reinnervation. Little is
      known about the changes in muscle activity and walking mechanics during
      midrecovery, i.e., the early reinnervation period that takes place between 5 and
      10 wk of recovery. Here, we investigated hindlimb mechanics and electromyogram
      (EMG) activity of ankle extensors in six cats during level and slope walking
      before and every 2 wk thereafter in a 14-wk period of recovery after the soleus
      (SO) and lateral gastrocnemius (LG) muscle nerves in one hindlimb were surgically
      transected and repaired. We found that the continued increase in SO and LG EMG
      magnitudes and corresponding changes in hindlimb mechanics coincided with the
      formation of neuromuscular synapses revealed in muscle biopsies. Throughout the
      recovery period, EMG magnitude of SO and LG during the stance phase and the
      duration of the stance-related activity were load dependent, similar to those in
      the intact synergistic medial gastrocnemius and plantaris. These results and the
      fact that EMG activity of ankle extensors and locomotor mechanics during level
      and upslope walking recovered 14 wk after nerve transection and repair suggest
      that loss of the stretch reflex in self-reinnervated muscles may be compensated
      by the recovered force-dependent feedback in self-reinnervated muscles, by
      increased central drive, and by increased gain in intermuscular motion-dependent
      pathways from intact ankle extensors. NEW & NOTEWORTHY This study provides new
      evidence that the timeline for functional recovery of gait after peripheral nerve
      injury and repair is consistent with the time required for neuromuscular
      junctions to form and muscles to reach preoperative tensions. Our findings
      suggest that a permanent loss of autogenic stretch reflex in self-reinnervated
      muscles may be compensated by recovered intermuscular force-dependent and
      oligosynaptic length-dependent feedback and central drive to regain adequate
      locomotor output capabilities during level and upslope walking.

PMID- 29187560
TI  - Multi-omics Approach Reveals Distinct Differences in Left- and Right-Sided Colon
      Cancer.
AB  - Increasing evidence suggests that left-sided colon cancer (LCC) and right-sided
      colon cancer (RCC) are emerging as two different colorectal cancer types with
      distinct clinical characteristics. However, the discrepancy in the underlying
      molecular event between these types of cancer has not been thoroughly elucidated
      to date and warrants comprehensive investigation. To this end, an integrated
      dataset from The Cancer Genome Atlas was used to compare and contrast LCC and
      RCC, covering mutation, DNA methylation, gene expression, and miRNA. Briefly, the
      signaling pathway cross-talk is more prevalent in RCC than LCC, such as RCC
      specific PI3K pathway, which often exhibits cross-talk with the RAS and P53
      pathways. Meanwhile, methylation signatures revealed that RCC was hypermethylated
      relative to LCC. In addition, differentially expressed genes (n = 253) and
      differentially expressed miRNAs (n = 16) were determined between LCC and RCC.
      Especially for Prostate Cancer Susceptibility Candidate 1 (PRAC1), a gene that
      was closely associated with hypermethylation, was the top significantly
      downregulated gene in RCC. Multi-omics comparison of LCC and RCC suggests that
      there are more aggressive markers in RCC and that tumor heterogeneity occurs
      within the location-based subtypes of colon cancer. These results clarify the
      debate regarding the conflicting prognosis between LCC and RCC, as proposed by
      different studies.Implications: The underlying molecular features present in LCC
      and RCC identified in this study are beneficial for adopting reasonable
      therapeutic approaches to prolong overall survival and progression-free survival
      in colorectal cancer patients. Mol Cancer Res; 16(3); 476-85. (c)2017 AACR.

PMID- 29187559
TI  - Reprograming of Glucose Metabolism by Zerumbone Suppresses Hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is the most prevalent and highly aggressive liver
      malignancy with limited therapeutic options. Here, the therapeutic potential of
      zerumbone, a sesquiterpene derived from the ginger plant Zingiber zerumbet,
      against HCC was explored. Zerumbone inhibited proliferation and clonogenic
      survival of HCC cells in a dose-dependent manner by arresting cells at the G2-M
      phase and inducing apoptosis. To elucidate the underlying molecular mechanisms, a
      phosphokinase array was performed that showed significant inhibition of the
      PI3K/AKT/mTOR and STAT3 signaling pathways in zerumbone-treated HCC cells. Gene
      expression profiling using microarray and analysis of microarray data by Gene Set
      Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) revealed that
      zerumbone treatment resulted in significant deregulation of genes regulating
      apoptosis, cell cycle, and metabolism. Indeed, tracing glucose metabolic pathways
      by growing HCC cells with 13C6-glucose and measuring extracellular and
      intracellular metabolites by 2D nuclear magnetic resonance (NMR) spectroscopy
      showed a reduction in glucose consumption and reduced lactate production,
      suggesting glycolytic inhibition. In addition, zerumbone impeded shunting of
      glucose-6-phosphate through the pentose phosphate pathway, thereby forcing tumor
      cells to undergo cell-cycle arrest and apoptosis. Importantly, zerumbone
      treatment suppressed subcutaneous and orthotopic growth and lung metastasis of
      HCC xenografts in immunocompromised mice. In conclusion, these findings reveal a
      novel and potentially effective therapeutic strategy for HCC using a natural
      product that targets cancer cell metabolism.Implications: Dietary compounds, like
      zerumbone, that impact cell cycle, apoptosis, and metabolic processes may have
      therapeutic benefits for HCC patients. Mol Cancer Res; 16(2); 256-68. (c)2017
      AACR.

PMID- 29187561
TI  - A Real Pain: Diagnostic Quandaries and Septic Arthritis.
AB  - Rapid diagnosis and treatment of an infected joint are paramount in preserving
      orthopedic function. Here, we present a brief review of the many challenges
      associated with the diagnosis of both septic arthritis and prosthetic joint
      infections. We also discuss the many laboratory tests currently available to aid
      in the accurate diagnosis of joint infection, as well as emerging diagnostics
      that may have future utility in the diagnosis of these challenging clinical
      entities.

PMID- 29187562
TI  - Development and Validation of a Real-Time PCR Assay for Rapid Detection of
      Candida auris from Surveillance Samples.
AB  - Candida auris is an emerging multidrug-resistant yeast causing invasive health
      care-associated infection with high mortality worldwide. Rapid identification of
      C. auris is of primary importance for the implementation of public health
      measures to control the spread of infection. To achieve these goals, we developed
      and validated a TaqMan-based real-time PCR assay targeting the internal
      transcribed spacer 2 (ITS2) region of the ribosomal gene. The assay was highly
      specific, reproducible, and sensitive, with the detection limit of 1 C. auris
      CFU/PCR. The performance of the C. auris real-time PCR assay was evaluated by
      using 623 surveillance samples, including 365 patient swabs and 258 environmental
      sponges. Real-time PCR yielded positive results from 49 swab and 58 sponge
      samples, with 89% and 100% clinical sensitivity with regard to their respective
      culture-positive results. The real-time PCR also detected C. auris DNA from 1%
      and 12% of swab and sponge samples with culture-negative results, indicating the
      presence of dead or culture-impaired C. auris The real-time PCR yielded results
      within 4 h of sample processing, compared to 4 to 14 days for culture, reducing
      turnaround time significantly. The new real-time PCR assay allows for accurate
      and rapid screening of C. auris and can increase effective control and prevention
      of this emerging multidrug-resistant fungal pathogen in health care facilities.

PMID- 29187563
TI  - Automated Interpretation of Blood Culture Gram Stains by Use of a Deep
      Convolutional Neural Network.
AB  - Microscopic interpretation of stained smears is one of the most operator
      dependent and time-intensive activities in the clinical microbiology laboratory.
      Here, we investigated application of an automated image acquisition and
      convolutional neural network (CNN)-based approach for automated Gram stain
      classification. Using an automated microscopy platform, uncoverslipped slides
      were scanned with a 40* dry objective, generating images of sufficient resolution
      for interpretation. We collected 25,488 images from positive blood culture Gram
      stains prepared during routine clinical workup. These images were used to
      generate 100,213 crops containing Gram-positive cocci in clusters, Gram-positive
      cocci in chains/pairs, Gram-negative rods, or background (no cells). These
      categories were targeted for proof-of-concept development as they are associated
      with the majority of bloodstream infections. Our CNN model achieved a
      classification accuracy of 94.9% on a test set of image crops. Receiver operating
      characteristic (ROC) curve analysis indicated a robust ability to differentiate
      between categories with an area under the curve of >0.98 for each. After training
      and validation, we applied the classification algorithm to new images collected
      from 189 whole slides without human intervention. Sensitivity and specificity
      were 98.4% and 75.0% for Gram-positive cocci in chains and pairs, 93.2% and 97.2%
      for Gram-positive cocci in clusters, and 96.3% and 98.1% for Gram-negative rods.
      Taken together, our data support a proof of concept for a fully automated
      classification methodology for blood-culture Gram stains. Importantly, the
      algorithm was highly adept at identifying image crops with organisms and could be
      used to present prescreened, classified crops to technologists to accelerate
      smear review. This concept could potentially be extended to all Gram stain
      interpretive activities in the clinical laboratory.

PMID- 29187564
TI  - A Comparison of Aspergillus and Mucorales PCR Testing of Different
      Bronchoalveolar Lavage Fluid Fractions from Patients with Suspected Invasive
      Pulmonary Fungal Disease.
AB  - In patients with hematological malignancies, bronchoalveolar lavage fluid (BALF)
      specimens are commonly used for the diagnosis of mold infections. However, it is
      not clear whether the cell pellet (P) or the supernatant fraction (S) of the BALF
      specimen is optimal for molecular diagnostic testing. Thus, 99 BALF specimens
      were collected from 96 hematology patients with or without allogeneic
      hematopoietic stem cell transplant. The cell pellets and supernatants were
      processed alone and in combination (S/P) for testing by two fungus-specific real
      time PCR assays compliant with international recommendations. The results
      achieved with S/P were revealed to be superior in comparison to those achieved
      with S and P alone, with the use of each single fraction showing a reduced
      sensitivity for the detection of Aspergillus DNA (82% and 43% for S and P,
      respectively). In 57% of the samples, testing of the combination of S and P
      generated a lower quantification cycle value than testing of S or P alone. Molds
      would have been missed in 5 and 16 out of 28 samples if only S or P,
      respectively, was analyzed. No sample was positive by testing of S or P only.
      Similar results were obtained for the detection of Mucorales DNA in BALF
      specimens (reduced sensitivity of 67% and 50% for S and P, respectively). Study
      patients were categorized according to the current European Organization for the
      Research and Treatment of Cancer/Mycoses Study Group classification for invasive
      fungal disease (IFD), revealing that 35 patients had proven/probable IFD (36%),
      47 patients had possible IFD (49%), and 14 patients had undetermined IFD (15%).

PMID- 29187565
TI  - Evaluation of Oxacillin and Cefoxitin Disk Diffusion and MIC Breakpoints
      Established by the Clinical and Laboratory Standards Institute for Detection of
      mecA-Mediated Oxacillin Resistance in Staphylococcus schleiferi.
AB  - Staphylococcus schleiferi is a beta-hemolytic, coagulase-variable colonizer of
      small animals that can cause opportunistic infections in humans. In veterinary
      isolates, the rate of mecA-mediated oxacillin resistance is significant, with
      reported resistance rates of >39%. The goal of this study was to evaluate
      oxacillin and cefoxitin disk diffusion (DD) and MIC breakpoints for detection of
      mecA-mediated oxacillin resistance in 52 human and 38 veterinary isolates of S.
      schleiferi Isolates were tested on multiple brands of commercial media and
      according to Clinical and Laboratory Standards Institute (CLSI) methods. Zone
      diameters and MIC values were interpreted using CLSI breakpoints (CLSI,
      Performance Standards for Antimicrobial Susceptibility Testing. M100-S27, 2017)
      for Staphylococcus aureus/Staphylococcus lugdunensis, coagulase-negative
      staphylococci (CoNS), and Staphylococcus pseudintermedius Results were compared
      to those of mecA PCR. Twenty-nine of 90 (32%) isolates were mecA positive.
      Oxacillin inhibition zone sizes and MICs interpreted by S. pseudintermedius
      breakpoints reliably differentiated mecA-positive and mecA-negative isolates,
      with a categorical agreement (CA) of 100% and no very major errors (VMEs) or
      major errors (MEs) for all media. For cefoxitin DD results interpreted using S.
      aureus/S. lugdunensis and CoNS breakpoints, CA values were 85% and 75%,
      respectively, and there were 72% and 64% VMEs, respectively, and 0 MEs. For
      cefoxitin MICs interpreted using S. aureus/S. lugdunensis breakpoints, CA was
      81%, and there were 60% VMEs and no MEs. Our data demonstrate that oxacillin DD
      or MIC testing methods using the current S. pseudintermedius breakpoints reliably
      identify mecA-mediated oxacillin resistance in S. schleiferi, while cefoxitin DD
      and MIC testing methods perform poorly.

PMID- 29187566
TI  - Stage-Specific Gene Profiling of Germinal Cells Helps Delineate the
      Mitosis/Meiosis Transition.
AB  - In flowering plants, germ lines are induced from somatic meristems within
      reproductive organs. Within anthers, germinal cell initials first undergo several
      rounds of mitotic proliferation before synchronously entering meiosis. Our
      understanding of the progression and the molecular basis of this mitosis to
      meiosis transition is still limited. Taking advantage of the correlation between
      anther length and premeiotic germinal cell development in maize (Zea mays), we
      studied the transcriptome dynamics of germinal cells at three sequential stages,
      mitotic archesporial cells, enlarging pollen mother cells at the premeiosis
      interphase, and pollen mother cells at the early prophase of meiosis, using laser
      microdissection-based expression profiling. Our analysis showed that cells
      undergoing the mitosis-meiosis switch exhibit robust transcriptional changes. The
      three stages are distinguished by the expression of genes encoding transcription
      factor subsets, meiotic chromosome recombination proteins, and distinct E3
      ubiquitin ligases, respectively. The transcription level of genes encoding
      protein turnover machinery was significantly higher in these three stages of
      germinal cells than in mature pollen, parenchyma cells, or seedlings. Our
      experimental results further indicate that many meiotic genes are not only
      transcribed, but also translated prior to meiosis. We suggest that the enlarging
      pollen mother cells stage represents a crucial turning point from mitosis to
      meiosis for developing germinal cells.

PMID- 29187567
TI  - Linking PHYTOCHROME-INTERACTING FACTOR to Histone Modification in Plant Shade
      Avoidance.
AB  - Shade avoidance syndrome (SAS) allows a plant grown in a densely populated
      environment to maximize opportunities to access to sunlight. Although it is well
      established that SAS is accompanied by gene expression changes, the underlying
      molecular mechanism needs to be elucidated. Here, we identify the
      H3K4me3/H3K36me3-binding proteins, Morf Related Gene (MRG) group proteins MRG1
      and MRG2, as positive regulators of shade-induced hypocotyl elongation in
      Arabidopsis (Arabidopsis thaliana). MRG2 binds PHYTOCHROME-INTERACTING FACTOR7
      (PIF7) and regulates the expression of several common downstream target genes,
      including YUCCA8 and IAA19 involved in the auxin biosynthesis or response pathway
      and PRE1 involved in brassinosteroid regulation of cell elongation. In response
      to shade, PIF7 and MRG2 are enriched at the promoter and gene-body regions and
      are necessary for increase of histone H4 and H3 acetylation to promote target
      gene expression. Our study uncovers a mechanism in which the shade-responsive
      factor PIF7 recruits MRG1/MRG2 that binds H3K4me3/H3K36me3 and brings histone
      acetylases to induce histone acetylations to promote expression of shade
      responsive genes, providing thus a molecular mechanistic link coupling the
      environmental light to epigenetic modification in regulation of hypocotyl
      elongation in plant SAS.

PMID- 29187569
TI  - Dynamics of Ethylene Production in Response to Compatible Nod Factor.
AB  - Establishment of symbiotic nitrogen-fixation in legumes is regulated by the plant
      hormone ethylene, but it has remained unclear whether and how its biosynthesis is
      regulated by the symbiotic pathway. We established a sensitive ethylene detection
      system for Lotus japonicus and found that ethylene production increased as early
      as 6 hours after inoculation with Mesorhizobium loti This ethylene response was
      dependent on Nod factor production by compatible rhizobia. Analyses of nodulation
      mutants showed that perception of Nod factor was required for ethylene emission,
      while downstream transcription factors including CYCLOPS, NIN, and ERN1 were not
      required for this response. Activation of the nodulation signaling pathway in
      spontaneously nodulating mutants was also sufficient to elevate ethylene
      production. Ethylene signaling is controlled by EIN2, which is duplicated in L.
      japonicus We obtained a L. japonicus Ljein2a Ljein2b double mutant that exhibits
      complete ethylene insensitivity and confirms that these two genes act redundantly
      in ethylene signaling. Consistent with this redundancy, both LjEin2a and LjEin2b
      are required for negative regulation of nodulation and Ljein2a Ljein2b double
      mutants are hypernodulating and hyperinfected. We also identified an unexpected
      role for ethylene in the onset of nitrogen fixation, with the Ljein2a Ljein2b
      double mutant showing severely reduced nitrogen fixation. These results
      demonstrate that ethylene production is an early and sustained nodulation
      response that acts at multiple stages to regulate infection, nodule
      organogenesis, and nitrogen fixation in L. japonicus.

PMID- 29187568
TI  - Molecular Mechanisms of Photoadaptation of Photosystem I Supercomplex from an
      Evolutionary Cyanobacterial/Algal Intermediate.
AB  - The monomeric photosystem I-light-harvesting antenna complex I (PSI-LHCI)
      supercomplex from the extremophilic red alga Cyanidioschyzon merolae represents
      an intermediate evolutionary link between the cyanobacterial PSI reaction center
      and its green algal/higher plant counterpart. We show that the C. merolae PSI
      LHCI supercomplex is characterized by robustness in various extreme conditions.
      By a combination of biochemical, spectroscopic, mass spectrometry, and electron
      microscopy/single particle analyses, we dissected three molecular mechanisms
      underlying the inherent robustness of the C. merolae PSI-LHCI supercomplex: (1)
      the accumulation of photoprotective zeaxanthin in the LHCI antenna and the PSI
      reaction center; (2) structural remodeling of the LHCI antenna and adjustment of
      the effective absorption cross section; and (3) dynamic readjustment of the
      stoichiometry of the two PSI-LHCI isomers and changes in the oligomeric state of
      the PSI-LHCI supercomplex, accompanied by dissociation of the PsaK core subunit.
      We show that the largest low light-treated C. merolae PSI-LHCI supercomplex can
      bind up to eight Lhcr antenna subunits, which are organized as two rows on the
      PsaF/PsaJ side of the core complex. Under our experimental conditions, we found
      no evidence of functional coupling of the phycobilisomes with the PSI-LHCI
      supercomplex purified from various light conditions, suggesting that the putative
      association of this antenna with the PSI supercomplex is absent or may be lost
      during the purification procedure.

PMID- 29187570
TI  - The Transcription Factor COL12 Is a Substrate of the COP1/SPA E3 Ligase and
      Regulates Flowering Time and Plant Architecture.
AB  - The ambient light environment controls many aspects of plant development
      throughout a plant's life cycle. Such complex control is achieved because a key
      repressor of light signaling, the Arabidopsis (Arabidopsis thaliana) COP1/SPA E3
      ubiquitin ligase causes the degradation of multiple regulators of endogenous
      developmental pathways. This includes the CONSTANS (CO) transcription factor that
      is responsible for photoperiodic control of flowering time. There are 16 CO-like
      proteins whose functions are only partly understood. Here, we show that 14 CO
      like (COL) proteins bind CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) and SUPPRESSOR
      OF PHYTOCHROME A-105 (SPA)1 in vitro. We subsequently focused on COL12 and show
      that COL12 binds COP1 and SPA proteins in vivo. The COL12 protein is degraded in
      darkness in a COP1-dependent fashion, indicating that COL12 is a substrate of the
      COP1/SPA ubiquitin ligase. Overexpression of COL12 causes late flowering
      specifically in long day conditions by decreasing the expression of FLOWERING
      LOCUS T This phenotype is genetically dependent on CO. Consistent with this
      finding, COL12 physically interacts with CO in vivo, suggesting that COL12
      represses flowering by inhibiting CO protein function. We show that COL12
      overexpression did not alter CO protein stability. It is therefore likely that
      COL12 represses the activity of CO rather than CO levels. Overexpression of COL12
      also affects plant architecture by increasing the number of rosette branches and
      reducing inflorescence height. These phenotypes are CO independent. Hence, we
      suggest that COL12 affects plant development through CO-dependent and CO
      independent mechanisms.

PMID- 29187572
TI  - The Scientific Society Publisher Alliance delivers an important message.

PMID- 29187573
TI  - Correction for Distinct effects of tubulin isotype mutations on neurite growth in
      Caenorhabditis elegans.

PMID- 29187571
TI  - The Brassicaceae Family Displays Divergent, Shoot-Skewed NLR Resistance Gene
      Expression.
AB  - Nucleotide-binding site leucine-rich repeat resistance genes (NLRs) allow plants
      to detect microbial effectors. We hypothesized that NLR expression patterns could
      reflect organ-specific differences in effector challenge and tested this by
      carrying out a meta-analysis of expression data for 1,235 NLRs from nine plant
      species. We found stable NLR root/shoot expression ratios within species,
      suggesting organ-specific hardwiring of NLR expression patterns in anticipation
      of distinct challenges. Most monocot and dicot plant species preferentially
      expressed NLRs in roots. In contrast, Brassicaceae species, including oilseed
      rape (Brassica napus) and the model plant Arabidopsis (Arabidopsis thaliana),
      were unique in showing NLR expression skewed toward the shoot across multiple
      phylogenetically distinct groups of NLRs. The Brassicaceae are also outliers in
      the sense that they have lost the common symbiosis signaling pathway, which
      enables intracellular infection by root symbionts. While it is unclear if these
      two events are related, the NLR expression shift identified here suggests that
      the Brassicaceae may have evolved unique pattern-recognition receptors and
      antimicrobial root metabolites to substitute for NLR protection. Such innovations
      in root protection could potentially be exploited in crop rotation schemes or for
      enhancing root defense systems of non-Brassicaceae crops.

PMID- 29187574
TI  - Stu2 uses a 15-nm parallel coiled coil for kinetochore localization and
      concomitant regulation of the mitotic spindle.
AB  - XMAP215/Dis1 family proteins are potent microtubule polymerases, critical for
      mitotic spindle structure and dynamics. While microtubule polymerase activity is
      driven by an N-terminal tumor overexpressed gene (TOG) domain array, proper
      cellular localization is a requisite for full activity and is mediated by a C
      terminal domain. Structural insight into the C-terminal domain's architecture and
      localization mechanism remain outstanding. We present the crystal structure of
      the Saccharomyces cerevisiae Stu2 C-terminal domain, revealing a 15-nm parallel
      homodimeric coiled coil. The parallel architecture of the coiled coil has
      mechanistic implications for the arrangement of the homodimer's N-terminal TOG
      domains during microtubule polymerization. The coiled coil has two spatially
      distinct conserved regions: CRI and CRII. Mutations in CRI and CRII perturb the
      distribution and localization of Stu2 along the mitotic spindle and yield defects
      in spindle morphology including increased frequencies of mispositioned and
      fragmented spindles. Collectively, these data highlight roles for the Stu2
      dimerization domain as a scaffold for factor binding that optimally positions
      Stu2 on the mitotic spindle to promote proper spindle structure and dynamics.

PMID- 29187575
TI  - A role for the Smc3 hinge domain in the maintenance of sister chromatid cohesion.
AB  - Cohesin is a conserved protein complex required for sister chromatid cohesion,
      chromosome condensation, DNA damage repair, and regulation of transcription.
      Although cohesin functions to tether DNA duplexes, the contribution of its
      individual domains to this activity remains poorly understood. We interrogated
      the Smc3p subunit of cohesin by random insertion mutagenesis. Analysis of a
      mutant in the Smc3p hinge revealed an unexpected role for this domain in cohesion
      maintenance and condensation. Further investigation revealed that the Smc3p hinge
      functions at a step following cohesin's stable binding to chromosomes and
      independently of Smc3p's regulation by the Eco1p acetyltransferase. Hinge mutant
      phenotypes resemble loss of Pds5p, which binds opposite the hinge near Smc3p's
      head domain. We propose that a specific conformation of the Smc3p hinge and Pds5p
      cooperate to promote cohesion maintenance and condensation.

PMID- 29187576
TI  - Host cell perforation by listeriolysin O (LLO) activates a Ca2+-dependent
      cPKC/Rac1/Arp2/3 signaling pathway that promotes Listeria monocytogenes
      internalization independently of membrane resealing.
AB  - Host cell invasion is an indispensable step for a successful infection by
      intracellular pathogens. Recent studies identified pathogen-induced host cell
      plasma membrane perforation as a novel mechanism used by diverse pathogens
      (Trypanosoma cruzi, Listeria monocytogenes, and adenovirus) to promote their
      internalization into target cells. It was concluded that T. cruzi and adenovirus
      damage the host cell plasma membrane to hijack the endocytic-dependent membrane
      resealing machinery, thereby invading the host cell. We studied L. monocytogenes
      and its secreted pore-forming toxin listeriolysin O (LLO) to identify key
      signaling events activated upon plasma membrane perforation that lead to
      bacterial internalization. Using various approaches, including fluorescence
      resonance energy transfer imaging, we found that the influx of extracellular Ca2+
      subsequent to LLO-mediated plasma membrane perforation is required for the
      activation of a conventional protein kinase C (cPKC). cPKC is positioned upstream
      of Rac1 and the Arp2/3 complex, which activation leads to F-actin--dependent
      bacterial internalization. Inhibition of this pathway did not prevent membrane
      resealing, revealing that perforation-dependent L. monocytogenes endocytosis is
      distinct from the resealing machinery. These studies identified the LLO-dependent
      endocytic pathway of L. monocytogenes and support a novel model for pathogen
      uptake promoted by plasma membrane injury that is independent of membrane
      resealing.

PMID- 29187577
TI  - Prc1E and Kif4A control microtubule organization within and between large Xenopus
      egg asters.
AB  - The cleavage furrow in Xenopus zygotes is positioned by two large microtubule
      asters that grow out from the poles of the first mitotic spindle. Where these
      asters meet at the midplane, they assemble a disk-shaped interaction zone
      consisting of anti-parallel microtubule bundles coated with chromosome passenger
      complex (CPC) and centralspindlin that instructs the cleavage furrow. Here we
      investigate the mechanism that keeps the two asters separate and forms a distinct
      boundary between them, focusing on the conserved cytokinesis midzone proteins
      Prc1 and Kif4A. Prc1E, the egg orthologue of Prc1, and Kif4A were recruited to
      anti-parallel bundles at interaction zones between asters in Xenopus egg
      extracts. Prc1E was required for Kif4A recruitment but not vice versa.
      Microtubule plus-end growth slowed and terminated preferentially within
      interaction zones, resulting in a block to interpenetration that depended on both
      Prc1E and Kif4A. Unexpectedly, Prc1E and Kif4A were also required for radial
      order of large asters growing in isolation, apparently to compensate for the
      direction-randomizing influence of nucleation away from centrosomes. We propose
      that Prc1E and Kif4, together with catastrophe factors, promote "anti-parallel
      pruning" that enforces radial organization within asters and generates boundaries
      to microtubule growth between asters.

PMID- 29187578
TI  - Stu2 acts as a microtubule destabilizer in metaphase budding yeast spindles.
AB  - The microtubule-associated protein Stu2 (XMAP215) has the remarkable ability to
      act either as a polymerase or as a destabilizer of the microtubule plus end. In
      budding yeast, it is required for the dynamicity of spindle microtubules and also
      for kinetochore force generation. To understand how Stu2 contributes to these
      distinct activities, we analyzed the contributions of its functional domains to
      its localization and function. We find that Stu2 colocalizes with kinetochores
      using its TOG domains, which bind GTP-tubulin, a coiled-coil homodimerization
      domain, and a domain that interacts with plus-end interacting proteins. Stu2
      localization is also promoted by phosphorylation at a putative CDK1
      phosphorylation site located within its microtubule-binding basic patch.
      Surprisingly, however, we find that kinetochore force generation is uncorrelated
      with the amount of kinetochore-colocalized Stu2. These and other data imply that
      Stu2 colocalizes with kinetochores by recognizing growing microtubule plus ends
      within yeast kinetochores. We propose that Stu2 destabilizes these plus ends to
      indirectly contribute to the "catch-bond" activity of the kinetochores.

PMID- 29187579
TI  - Urinary Tract Infection Antibiotic Trial Study Design: A Systematic Review.
AB  - CONTEXT: Urinary tract infections (UTIs) represent common bacterial infections in
      children. No guidance on the conduct of pediatric febrile UTI clinical trials
      (CTs) exist. OBJECTIVE: To assess the criteria used for patient selection and the
      efficacy end points in febrile pediatric UTI CTs. DATA SOURCES: Medline, Embase,
      Cochrane central databases, and clinicaltrials.gov were searched between January
      1, 1990, and November 24, 2016. STUDY SELECTION: We combined Medical Subject
      Headings terms and free-text terms for "urinary tract infections" and
      "therapeutics" and "clinical trials" in children (0-18 years), identifying 3086
      articles. DATA EXTRACTION: Two independent reviewers assessed study quality and
      performed data extraction. RESULTS: We included 40 CTs in which a total of 4381
      cases of pediatric UTIs were investigated. Positive urine culture results and
      fever were the most common inclusion criteria (93% and 78%, respectively). Urine
      sampling method, pyuria, and colony thresholds were highly variable. Clinical and
      microbiological end points were assessed in 88% and 93% of the studies,
      respectively. Timing for end point assessment was highly variable, and only 3
      studies (17%) out of the 18 performed after the Food and Drug Administration 1998
      guidance publication assessed primary and secondary end points consistently with
      this guidance. LIMITATIONS: Our limitations included a mixed population of
      healthy children and children with an underlying condition. In 6 trials,
      researchers studied a subgroup of patients with afebrile UTI. CONCLUSIONS: We
      observed a wide variability in the microbiological inclusion criteria and the
      timing for end point assessment. The available guidance for adults appear not to
      be used by pediatricians and do not seem applicable to the childhood UTI. A
      harmonized design for pediatric UTIs CT is necessary.

PMID- 29187580
TI  - Computer-Aided Recognition of Facial Attributes for Fetal Alcohol Spectrum
      Disorders.
AB  - OBJECTIVES: To compare the detection of facial attributes by computer-based
      facial recognition software of 2-D images against standard, manual examination in
      fetal alcohol spectrum disorders (FASD). METHODS: Participants were gathered from
      the Fetal Alcohol Syndrome Epidemiology Research database. Standard frontal and
      oblique photographs of children were obtained during a manual, in-person
      dysmorphology assessment. Images were submitted for facial analysis conducted by
      the facial dysmorphology novel analysis technology (an automated system), which
      assesses ratios of measurements between various facial landmarks to determine the
      presence of dysmorphic features. Manual blinded dysmorphology assessments were
      compared with those obtained via the computer-aided system. RESULTS: Areas under
      the curve values for individual receiver-operating characteristic curves revealed
      the computer-aided system (0.88 +/- 0.02) to be comparable to the manual method
      (0.86 +/- 0.03) in detecting patients with FASD. Interestingly, cases of alcohol
      related neurodevelopmental disorder (ARND) were identified more efficiently by
      the computer-aided system (0.84 +/- 0.07) in comparison to the manual method
      (0.74 +/- 0.04). A facial gestalt analysis of patients with ARND also identified
      more generalized facial findings compared to the cardinal facial features seen in
      more severe forms of FASD. CONCLUSIONS: We found there was an increased
      diagnostic accuracy for ARND via our computer-aided method. As this category has
      been historically difficult to diagnose, we believe our experiment demonstrates
      that facial dysmorphology novel analysis technology can potentially improve ARND
      diagnosis by introducing a standardized metric for recognizing FASD-associated
      facial anomalies. Earlier recognition of these patients will lead to earlier
      intervention with improved patient outcomes.

PMID- 29187581
TI  - Randomized Trials in Children With UTI.

PMID- 29187582
TI  - Zhenbao pill protects against acute spinal cord injury via miR-146a-5p regulating
      the expression of GPR17.
AB  - The aim of the present study was to observe the effect of zhenbao pill on the
      motor function of acute spinal cord injury (ASCI) rats and the molecular
      mechanisms involving miR-146a-5p and G-protein-coupled receptor 17 (GPR17). ASCI
      rat model was established by modified Allen method, and then the rats were
      divided into three groups. SH-SY5Y cells were cultured overnight in hypoxia
      condition and transfected with miR-146a-5p mimic or miR-146a-5p inhibitor. The
      hind limb motor function of the rats was evaluated by Basso, Beattie, Bresnahan
      (BBB) scoring system. Quantitative real-time PCR (qRT-PCR) and Western blot were
      used to detect the expression of miR-146a-5p, GPR17, inducible nitric oxide
      synthase (iNOS), interleukin 1beta (IL-1beta), and tumor necrosis factor alpha
      (TNF-alpha). Neuronal apoptosis was measured using flow cytometry assay.
      Luciferase reporter assay was performed to determine the regulation of miR-146a
      5p on GPR17. Zhenbao pill could enhance hind limb motor function and attenuate
      the inflammatory response caused by ASCI. Moreover, zhenbao pill increased the
      level of miR-146a-5p and decreased GPR17 expression in vivo and in vitro
      Bioinformatics software predicted that GPR17 3'-UTR had a binding site with miR
      146a-5p Luciferase reporter assay showed that miR-146a-5p had a negative
      regulatory effect on GPR17 expression. Knockdown of miR-146a-5p could reverse the
      effect of zhenbao pill on the up-regulation of GPR17 induced by hypoxia, reversed
      the inhibitory effect of zhenbao pill on the cell apoptosis induced by hypoxia
      and the recovery of zhenbao pill on hind limb motor function in ASCI rats.
      Zhenbao pill could inhibit neuronal apoptosis by regulating miR-146a-5p/GPR17
      expression, and then promoting the recovery of spinal cord function.

PMID- 29187584
TI  - A novel bispecific c-MET/CTLA-4 antibody targeting lung cancer stem cell-like
      cells with therapeutic potential in human non-small cell lung cancer.
AB  - A novel paradigm in tumor biology suggests that non-small cell lung cancer
      (NSCLC) growth is driven by lung cancer stem cell-like cells (LCSCs), but here
      are still not any effective strategies to remove LCSCs. The bispecific antibody
      is a novel antibody, which can target two different antigens and mediate specific
      killing effects by selectively redirecting effector cells to the target cells.
      Here, we designed and synthesized a new bispecific antibody (BsAb), BsAb-5, that
      can target cellular-mesenchymal to epithelial transition factor (c-MET) and
      cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in CD166+ LCSCs with high
      affinity and specificity, for the first time. We showed that BsAb-5 could inhibit
      hepatocyte growth factor (HGF)-mediated tumor development, including
      proliferation, migration, and apoptosis, serving as an inhibitory c-MET antibody.
      Moreover, we demonstrated that mechanisms responsible for BsAb-5 in CD166+ LCSCs
      included inducing c-MET degradation and inhibition HGF-stimulated c-MET-Notch
      pathway by using AdHGF infection, nuclei location and western-blot assays. In
      vivo, xenograft analysis revealed that mice on BsAb-5 group showed significantly
      reduced tumor volume. At the meantime, the observed anti-tumor effects of BsAb-5
      were dependent on considerably suppressing Tregs and up-regulating effector T
      cells. On the basis of these results, we have identified a potential bispecific
      antibody drug, which can effectively target c-MET and CTLA-4 in CD166+ LCSCs for
      the treatment of human NSCLC.

PMID- 29187583
TI  - MiR-375 attenuates injury of cerebral ischemia/reperfusion via targetting Ctgf.
AB  - Ischemic stroke is the leading cause of disability and deaths worldwide. MiRNAs
      have been shown to play an important role in development and pathogenesis of the
      nervous system. However, the precise function and mechanism of miRNAs are not
      fully understood in the brain injury induced by ischemia/reperfusion (I/R).
      Herein, our study showed that miR-375 expression was significantly down-regulated
      in the rat I/R brain. With the in vivo and in vitro I/R stroke models, we found
      that miR-375 mimic provides significant protection from injury to cerebral I/R,
      which is reflected by reduced infarct volumes and cell apoptosis, and increased
      proliferation and migration of PC12 cells. Mechanistically, our findings showed
      that miR-375 binds to 3'-UTR region of Ctgf mRNA, subsequently leading to the
      decreased expression of Ctgf in the I/R brain. Furthermore, we showed that miR
      375/Ctgf-mediated protective effects are associated with p21/PI3K/Akt signaling
      pathways. Our findings thus provide a new insight into the mechanism of cerebral
      I/R injury and pave a potential new way for the therapy of cerebral I/R injury.

PMID- 29187585
TI  - miR-27b promotes type II collagen expression by targetting peroxisome
      proliferator-activated receptor-gamma2 during rat articular chondrocyte
      differentiation.
AB  - MicroRNAs (miRNAs) play an essential role in articular cartilage development and
      growth. However, the exact mechanisms involved in this process remain unknown. In
      the present study, we investigated the biological functions of miR-27b during
      hypertrophic differentiation of rat articular chondrocytes. Based on in situ
      hybridization and immunohistochemistry, we report that miR-27b expression is
      reduced in the hypertrophic zone of articular cartilage, but expression of
      peroxisome proliferator-activated receptor gamma (Ppargamma) is increased. Dual
      luciferase reporter gene assay and Western blot analysis demonstrated that
      Ppargamma2 is a target of miR-27b Overexpression of miR-27b inhibited expression
      of Ppargamma2, as well as type X collagen (Col10a1) and matrix metalloproteinase
      13 (Mmp13), while significantly promoting the expression of Sex-determining
      Region-box 9 (Sox9) and type II collagen (Col2a1) at both the mRNA and protein
      levels. Rosiglitazone, a Ppargamma agonist, suppressed Col2a1 expression, while
      promoting expression of runt-related transcription factor 2 (Runx2) and Col10a1
      in a concentration-dependent manner. siRNA-mediated knockdown of Ppargamma2
      caused an increase in protein levels of Col2a1. The present study demonstrates
      that miR-27b regulates chondrocyte hypertrophy in part by targetting Ppargamma2,
      and that miR-27b may have important therapeutic implications in cartilage
      diseases.

PMID- 29187586
TI  - Live Attenuated Leishmania donovani Centrin Gene-Deleted Parasites Induce IL-23
      Dependent IL-17-Protective Immune Response against Visceral Leishmaniasis in a
      Murine Model.
AB  - No vaccine exists against visceral leishmaniasis. To develop effective vaccines,
      we have previously reported protective role of live attenuated centrin gene
      deleted Leishmania donovani (LdCen-/- ) parasites through induction of Th1 type
      immune response in mice, hamsters, and dogs. In this study, we specifically
      explored the role of Th17 cells in LdCen-/- -induced host protection in mice. Our
      results showed that compared with wild-type L. donovani infection, LdCen-/-
      parasites induce significantly higher expression of Th17 differentiation
      cytokines in splenic dendritic cells. There was also induction of IL-17 and its
      promoting cytokines in total splenocytes and in both CD4 and CD8 T cells
      following immunization with LdCen-/- Upon challenge with wild-type parasites, IL
      17 and its differentiating cytokines were significantly higher in LdCen-/- 
      immunized mice compared with nonimmunized mice that resulted in parasite control.
      Alongside IL-17 induction, we observed induction of IFN-gamma-producing Th1 cells
      as reported earlier. However, Th17 cells are generated before Th1 cells.
      Neutralization of either IL-17 or IFN-gamma abrogated LdCen-/- -induced host
      protection further confirming the essential role of Th17 along with Th1 cytokines
      in host protection. Treatment with recombinant IL-23, which is required for
      stabilization and maintenance of IL-17, heightened Th17, and Tc17 responses in
      immunized mice splenocytes. In contrast, Th17 response was absent in immunized IL
      23R-/- mice that failed to induce protection upon virulent Leishmania challenge
      suggesting that IL-23 plays an essential role in IL-17-mediated protection by
      LdCen-/- parasites. This study unveiled the role of IL-23-dependent IL-17
      induction in LdCen-/- parasite-induced immunity and subsequent protection against
      visceral leishmaniasis.

PMID- 29187587
TI  - Modulation of the Alternative Pathway of Complement by Murine Factor H-Related
      Proteins.
AB  - Factor H (FH) is a key alternative pathway regulator that controls complement
      activation both in the fluid phase and on specific cell surfaces, thus allowing
      the innate immune response to discriminate between self and foreign pathogens.
      However, the interrelationships between FH and a group of closely related
      molecules, designated the FH-related (FHR) proteins, are currently not well
      understood. Whereas some studies have suggested that human FHR proteins possess
      complement regulatory abilities, recent studies have shown that FHR proteins are
      potent deregulators. Furthermore, the roles of the FHR proteins have not been
      explored in any in vivo models of inflammatory disease. In this study, we report
      the cloning and expression of recombinant mouse FH and three FHR proteins (FHR
      proteins A-C). Results from functional assays show that FHR-A and FHR-B proteins
      antagonize the protective function of FH in sheep erythrocyte hemolytic assays
      and increase cell-surface C3b deposition on a mouse kidney proximal tubular cell
      line (TEC) and a human retinal pigment epithelial cell line (ARPE-19). We also
      report apparent KD values for the binding interaction of mouse C3d with mouse FH
      (3.85 MUM), FHR-A (136 nM), FHR-B (546 nM), and FHR-C (1.04 MUM), which directly
      correlate with results from functional assays. Collectively, our work suggests
      that similar to their human counterparts, a subset of mouse FHR proteins have an
      important modulatory role in complement activation. Further work is warranted to
      define the in vivo context-dependent roles of these proteins and determine
      whether FHR proteins are suitable therapeutic targets for the treatment of
      complement-driven diseases.

PMID- 29187588
TI  - CXCR3/CXCL10 Axis Shapes Tissue Distribution of Memory Phenotype CD8+ T Cells in
      Nonimmunized Mice.
AB  - The preimmune repertoire consists of mature T lymphocytes that have not yet been
      stimulated in the periphery. Memory phenotype (MP) cells have been reported as
      part of the preimmune repertoire (i.e., T cells bearing memory markers despite
      lack of engagement with cognate Ag); however, little is known about their
      trafficking and function. In this study, we hypothesized that MP cells, naive to
      TCR stimulation, constitute a transient population that traffics to tissues
      during development. Using mutant and transgenic animals with a monospecific TCR,
      we discovered increased numbers of MP CD8+ T cells circulating in nonimmunized
      Cxcr3-/- and Cxcl10-/- mice compared with wild-type animals. Phenotypic
      differences included decreased numbers of preimmune MP Ag-specific T cells in the
      skin and thymus and a distinct pattern of activation upon TCR engagement. Our
      results show for the first time, to our knowledge, an important role for CXCR3
      and CXCL10 in the tissue distribution of preimmune MP cells.

PMID- 29187589
TI  - STAT5B: A Differential Regulator of the Life and Death of CD4+ Effector Memory T
      Cells.
AB  - Understanding the control of Ag restimulation-induced T cell death (RICD),
      especially in cancer immunotherapy, where highly proliferating T cells will
      encounter potentially large amounts of tumor Ags, is important now more than
      ever. It has been known that growth cytokines make T cells susceptible to RICD,
      but the precise molecular mediators that govern this in T cell subsets is unknown
      until now. STAT proteins are a family of transcription factors that regulate gene
      expression programs underlying key immunological processes. In particular, STAT5
      is known to favor the generation and survival of memory T cells. In this study,
      we report an unexpected role for STAT5 signaling in the death of effector memory
      T (TEM) cells in mice and humans. TEM cell death was prevented with neutralizing
      anti-IL-2 Ab or STAT5/JAK3 inhibitors, indicating that STAT5 signaling drives
      RICD in TEM cells. Moreover, we identified a unique patient with a heterozygous
      missense mutation in the coiled-coil domain of STAT5B that presented with
      autoimmune lymphoproliferative syndrome-like features. Similar to Stat5b-/- mice,
      this patient exhibited increased CD4+ TEM cells in the peripheral blood. The
      mutant STAT5B protein dominantly interfered with STAT5-driven transcriptional
      activity, leading to global downregulation of STAT5-regulated genes in patient T
      cells upon IL-2 stimulation. Notably, CD4+ TEM cells from the patient were
      strikingly resistant to cell death by in vitro TCR restimulation, a finding that
      was recapitulated in Stat5b-/- mice. Hence, STAT5B is a crucial regulator of RICD
      in memory T cells in mice and humans.

PMID- 29187590
TI  - Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell
      Damage after Renal Ischemia-Reperfusion Injury.
AB  - Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI),
      which is an increasing problem in the clinic and has been associated with
      elevated rates of mortality. Therapies to treat AKI are currently not available,
      so identification of new targets that can be modulated to ameliorate renal damage
      upon diagnosis of AKI is essential. In this study, a novel cannabinoid receptor 2
      (CB2) agonist, SMM-295 [3'-methyl-4-(2-(thiophen-2-yl)propan-2-yl)biphenyl-2,6
      diol], was designed, synthesized, and tested in vitro and in silico. Molecular
      docking of SMM-295 into a CB2 active-state homology model showed that SMM-295
      interacts well with key amino acids to stabilize the active state. In human
      embryonic kidney 293 cells, SMM-295 was capable of reducing cAMP production with
      66-fold selectivity for CB2 versus cannabinoid receptor 1 and dose-dependently
      increased mitogen-activated protein kinase and Akt phosphorylation. In vivo
      testing of the CB2 agonist was performed using a mouse model of bilateral IRI,
      which is a common model to mimic human AKI, where SMM-295 was immediately
      administered upon reperfusion of the kidneys after the ischemia episode.
      Histologic damage assessment 48 hours after reperfusion demonstrated reduced
      tubular damage in the presence of SMM-295. This was consistent with reduced
      plasma markers of renal dysfunction (i.e., creatinine and neutrophil gelatinase
      associated lipocalin) in SMM-295-treated mice. Mechanistically, kidneys treated
      with SMM-295 were shown to have elevated activation of Akt with reduced terminal
      deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling
      (TUNEL)-positive cells compared with vehicle-treated kidneys after IRI. These
      data suggest that selective CB2 receptor activation could be a potential
      therapeutic target in the treatment of AKI.

PMID- 29187592
TI  - Heterogeneity of respiratory disease in children and young adults with sickle
      cell disease.
AB  - To detect and characterise different phenotypes of respiratory disease in
      children and young adults with sickle cell disease (SCD), 11 lung function and
      haematological biomarkers were analysed using k-means cluster analysis in a
      cohort of 114 subjects with SCD aged between 5 and 27 years. Three clusters were
      detected: cluster 1 had elevated pulmonary capillary blood volume, mixed
      obstructive/restrictive lung disease, hypoxia and moderately severe anaemia;
      cluster 2 were older patients with restrictive lung disease; and cluster 3 were
      younger patients with obstructive lung disease, elevated serum lactate
      dehydrogenase and bronchodilator reversibility. These results may inform more
      personalised management strategies to improve outcomes.

PMID- 29187593
TI  - Ghost of chest drain past.

PMID- 29187591
TI  - MicroRNA dynamics at the onset of primordial germ and somatic cell sex
      differentiation during mouse embryonic gonad development.
AB  - In mammals, commitment and specification of germ cell lines involves complex
      programs that include sex differentiation, control of proliferation, and meiotic
      initiation. Regulation of these processes is genetically controlled by fine-tuned
      mechanisms of gene regulation in which microRNAs (miRNAs) are involved. We have
      characterized, by small-RNA-seq and bioinformatics analyses, the miRNA expression
      patterns of male and female mouse primordial germ cells (PGCs) and gonadal
      somatic cells at embryonic stages E11.5, E12.5, and E13.5. Differential
      expression analyses revealed differences in the regulation of key miRNA clusters
      such as miR-199-214, miR-182-183-96, and miR-34c-5p, whose targets have defined
      roles during gonadal sexual determination in both germ and somatic cells.
      Extensive analyses of miRNA sequences revealed an increase in noncanonical
      isoforms on PGCs at E12.5 and dramatic changes of 3' isomiR expression and 3'
      nontemplate nucleotide additions in female PGCs at E13.5. Additionally, RT-qPCR
      analyses of genes encoding proteins involved in miRNA biogenesis and 3'
      nucleotide addition uncovered sexually and developmentally specific expression,
      characterized by the decay of Drosha, Dgcr8, and Xpo5 expression along gonadal
      development. These results demonstrate that miRNAs, their isomiRs, and miRNA
      machinery are differentially regulated and participate actively in gonadal sexual
      differentiation in both PGCs and gonadal somatic cells.

PMID- 29187594
TI  - Plasma urate, lung function and chronic obstructive pulmonary disease: a
      Mendelian randomisation study in 114 979 individuals from the general population.
AB  - BACKGROUND: Urate is a strong antioxidant in plasma and may protect against lung
      function impairment. We tested the hypothesis that high plasma urate is causally
      associated with better lung function and low risk of respiratory symptoms and
      COPD. METHODS: We measured lung function and plasma urate in 114 979 individuals
      from the Copenhagen City Heart Study and the Copenhagen General Population Study
      and genotyped for SLC2A9 rs7442295 and ABCG2 rs2231142 variants, previously
      associated with high plasma urate, in 110 152 individuals. RESULTS: In the two
      studies combined, multivariable-adjusted 100 umol/L higher plasma urate was
      associated with -1.54% (95% CI -1.67 to -1.40) lower FEV1 % predicted and -1.57%
      (95% CI -1.69 to -1.44) lower FVC % predicted observationally; the corresponding
      estimates for genetically determined 100 umol/L higher plasma urate were -0.46%
      (95% CI -1.17 to 0.25) and -0.40% (95% CI -1.03 to 0.23). High plasma urate was
      also associated with higher risk of respiratory symptoms; however, genetically
      determined high plasma urate was not associated with respiratory symptoms.
      Finally, we identified 14 151 individuals with COPD and found ORs of 1.08 (95% CI
      1.06 to 1.11) for COPD observationally and 1.01 (95% CI 0.88 to 1.15) genetically
      per 100 umol/L higher plasma urate. CONCLUSION: High plasma urate was associated
      with worse lung function and higher risk of respiratory symptoms and COPD in
      observational analyses; however, genetically high plasma urate was not associated
      with any of these outcomes. Thus, our data do not support a direct causal
      relationship.

PMID- 29187595
TI  - Ubiquitin signaling and autophagy.
AB  - Ubiquitination is a widespread post-translational modification that controls
      multiple steps in autophagy, a major lysosome-mediated intracellular degradation
      pathway. A variety of ubiquitin chains are attached as selective labels on
      protein aggregates and dysfunctional organelles, thus promoting their autophagy
      dependent degradation. Moreover, ubiquitin modification of autophagy regulatory
      components is essential to positively or negatively regulate autophagy flux in
      both non-selective and selective pathways. We review the current findings that
      elucidate the components, timing, and kinetics of the multivalent role of
      ubiquitin signals in control of amplitude and selectivity of autophagy pathways
      as well as their impact on the development of human diseases.

PMID- 29187596
TI  - The dUTPase of white spot syndrome virus assembles its active sites in a
      noncanonical manner.
AB  - dUTPases are essential enzymes for maintaining genome integrity and have recently
      been shown to play moonlighting roles when containing extra sequences.
      Interestingly, the trimeric dUTPase of white spot syndrome virus (wDUT) harbors a
      sequence insert at the position preceding the C-terminal catalytic motif V (pre-V
      insert), rarely seen in other dUTPases. However, whether this extra sequence
      endows wDUT with additional properties is unknown. Herein, we present the crystal
      structures of wDUT in both ligand-free and ligand-bound forms. We observed that
      the pre-V insert in wDUT forms an unusual beta-hairpin structure in the domain
      swapping region and thereby facilitates a unique orientation of the adjacent C
      terminal segment, positioning the catalytic motif V onto the active site of its
      own subunit instead of a third subunit. Consequently, wDUT employs two-subunit
      active sites, unlike the widely accepted paradigm that the active site of
      trimeric dUTPase is contributed by all three subunits. According to results from
      local structural comparisons, the active-site configuration of wDUT is similar to
      that of known dUTPases. However, we also found that residues in the second-shell
      region of the active site are reconfigured in wDUT as an adaption to its unique C
      terminal orientation. We also show that deletion of the pre-V insert
      significantly reduces wDUT's enzymatic activity and thermal stability. We
      hypothesize that this rare structural arrangement confers additional
      functionality to wDUT. In conclusion, our study expands the structural diversity
      in the conserved dUTPase family and illustrates how sequence insertion and amino
      acid substitution drive protein evolution cooperatively.

PMID- 29187597
TI  - Emerging roles of transcriptional enhancers in chromatin looping and promoter
      proximal pausing of RNA polymerase II.
AB  - Initiation and regulation of transcription by RNA polymerase II (RNAPII) in
      eukaryotes rely on the transcriptional regulatory elements. Promoters and
      enhancers share similar architectures and functions, and the prevailing view is
      that they can initiate bidirectional transcription. We summarize functional roles
      of enhancer transcription and possible mechanisms in enhancer-promoter
      communication. We discuss the potential roles of enhancer RNAs (eRNAs) in early
      elongation and highlight that transcriptional enhancers might modulate the
      release of paused RNAPII via 3D chromatin looping. Emerging evidence suggests
      that transcriptional enhancers regulate the promoter-proximal pausing of RNAPII,
      a key rate-limiting step required for productive elongation.

PMID- 29187598
TI  - Epitope-focused immunogens against the CD4-binding site of HIV-1 envelope protein
      induce neutralizing antibodies against auto- and heterologous viruses.
AB  - Recent discoveries of broadly neutralizing antibodies (bnAbs) in HIV-1-infected
      individuals have led to the identification of several major "vulnerable sites" on
      the HIV-1 envelope (Env) glycoprotein. These sites have provided precise targets
      for HIV-1 vaccine development, but identifying and utilizing many of these
      targets remain technically challenging. Using a yeast surface display-based
      approach, we sought to identify epitope-focused antigenic domains (EADs)
      containing one of the "vulnerable sites," the CD4-binding site (CD4bs), through
      screening and selection of a combinatorial antigen library of the HIV-1 envelope
      glycoprotein with the CD4bs bnAb VRC01. We isolated multiple EADs and found that
      their trimeric forms have biochemical and structural features that preferentially
      bind and activate B cells that express VRC01 in vitro More importantly, these
      EADs could induce detectable levels of neutralizing antibodies against
      genetically related autologous and heterologous subtype B viruses in guinea pigs.
      Our results demonstrate that an epitope-focused approach involving a screen of a
      combinatorial antigen library is feasible. The EADs identified here represent a
      promising collection of possible targets in the rational design of HIV-1 vaccines
      and lay the foundation for harnessing the specific antigenicity of CD4bs for
      protective immunogenicity in vivo.

PMID- 29187599
TI  - Oligomannosidic glycans at Asn-110 are essential for secretion of human diamine
      oxidase.
AB  - N-Glycosylation plays a fundamental role in many biological processes. Human
      diamine oxidase (hDAO), required for histamine catabolism, has multiple N
      glycosylation sites, but their roles, for example in DAO secretion, are unclear.
      We recently reported that the N-glycosylation sites Asn-168, Asn-538, and Asn-745
      in recombinant hDAO (rhDAO) carry complex-type glycans, whereas Asn-110 carries
      only mammalian-atypical oligomannosidic glycans. Here, we show that Asn-110 in
      native hDAO from amniotic fluid and Caco-2 cells, DAO from porcine kidneys, and
      rhDAO produced in two different HEK293 cell lines is also consistently occupied
      by oligomannosidic glycans. Glycans at Asn-168 were predominantly sialylated with
      bi- to tetra-antennary branches, and Asn-538 and Asn-745 had similar complex-type
      glycans with some tissue- and cell line-specific variations. The related copper
      containing amine oxidase human vascular adhesion protein-1 also exclusively
      displayed high-mannose glycosylation at Asn-137. X-ray structures revealed that
      the residues adjacent to Asn-110 and Asn-137 form a highly conserved hydrophobic
      cleft interacting with the core trisaccharide. Asn-110 replacement with Gln
      completely abrogated rhDAO secretion and caused retention in the endoplasmic
      reticulum. Mutations of Asn-168, Asn-538, and Asn-745 reduced rhDAO secretion by
      13, 71, and 32%, respectively. Asn-538/745 double and Asn-168/538/745 triple
      substitutions reduced rhDAO secretion by 85 and 94%. Because of their locations
      in the DAO structure, Asn-538 and Asn-745 glycosylations might be important for
      efficient DAO dimer formation. These functional results are reflected in the high
      evolutionary conservation of all four glycosylation sites. Human DAO is abundant
      only in the gastrointestinal tract, kidney, and placenta, and glycosylation seems
      essential for reaching high enzyme expression levels in these tissues.

PMID- 29187601
TI  - Efficient solid-phase synthesis of meningococcal capsular oligosaccharides
      enables simple and fast chemoenzymatic vaccine production.
AB  - Neisseria meningitidis serogroups A and X are among the leading causes of
      bacterial meningitis in the African meningitis belt. Glycoconjugate vaccines,
      consisting of an antigenic carrier protein coupled to the capsular polysaccharide
      of the bacterial pathogen, are the most effective strategy for prevention of
      meningococcal disease. However, the distribution of effective glycoconjugate
      vaccines in this region is limited by the high cost of cultivating pathogens and
      purification of their capsular polysaccharides. Moreover, chemical approaches to
      synthesize oligosaccharide antigens have proven challenging. In the current
      study, we present a chemoenzymatic approach for generating tailored
      oligosaccharide fractions ready for activation and coupling to the carrier
      protein. In a first step, the elongation modes of recombinant capsular
      polymerases from Neisseria meningitidis serogroups A (CsaB) and X (CsxA) were
      characterized. We observed that CsaB is a distributive enzyme, and CsxA is a
      processive enzyme. Sequence comparison of these two stealth family proteins
      revealed a C-terminal extension in CsxA, which conferred processivity because of
      the existence of a second product-binding site. Deletion of the C-terminal domain
      converted CsxA into a distributive enzyme, allowing facile control of product
      length by adjusting the ratio of donor to acceptor sugars. Solid-phase fixation
      of the engineered capsular polymerases enabled rapid production of capsular
      polysaccharides with high yield and purity. In summary, the tools developed here
      provide critical steps toward reducing the cost of conjugate vaccine production,
      which will increase access in regions with the greatest need. Our work also
      facilitates efforts to study the relationship between oligosaccharide size and
      antigenicity.

PMID- 29187600
TI  - De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6
      (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic
      epithelium.
AB  - Aberrant expression of O-glycans is a hallmark of epithelial cancers. Mucin-type
      O-glycosylation is initiated by a large family of UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferases (GalNAc-Ts) that target different proteins and
      are differentially expressed in cells and organs. Here, we investigated the
      expression patterns of all of the GalNAc-Ts in colon cancer by analyzing
      transcriptomic data. We found that GalNAc-T6 was highly up-regulated in colon
      adenocarcinomas but absent in normal-appearing adjacent colon tissue. These
      results were verified by immunohistochemistry, suggesting that GalNAc-T6 plays a
      role in colon carcinogenesis. To investigate the function of GalNAc-T6 in colon
      cancer, we used precise gene targeting to produce isogenic colon cancer cell
      lines with a knockout/rescue system for GALNT6 GalNAc-T6 expression was
      associated with a cancer-like, dysplastic growth pattern, whereas GALNT6 knockout
      cells showed a more normal differentiation pattern, reduced proliferation,
      normalized cell-cell adhesion, and formation of crypts in tissue cultures. O
      Glycoproteomic analysis of the engineered cell lines identified a small set of
      GalNAc-T6-specific targets, suggesting that this isoform has unique cellular
      functions. In support of this notion, the genetically and functionally closely
      related GalNAc-T3 homolog did not show compensatory functionality for effects
      observed for GalNAc-T6. Taken together, these data strongly suggest that aberrant
      GalNAc-T6 expression and site-specific glycosylation is involved in oncogenic
      transformation.

PMID- 29187602
TI  - TMEM16A and TMEM16B channel proteins generate Ca2+-activated Cl- current and
      regulate melatonin secretion in rat pineal glands.
AB  - Pinealocytes regulate circadian rhythm by synthesizing and secreting melatonin.
      These cells generate action potentials; however, the contribution of specific ion
      channels to melatonin secretion from pinealocytes remains unclear. In this study,
      the involvement and molecular identity of Ca2+-activated Cl- (ClCa) channels in
      the regulation of melatonin secretion were examined in rat pineal glands.
      Treatment with the ClCa channel blockers, niflumic acid or T16Ainh-A01,
      significantly reduced melatonin secretion in pineal glands. After pineal K+
      currents were totally blocked under whole-cell patch clamp conditions,
      depolarization and subsequent repolarization induced a slowly activating outward
      current and a substantial inward tail current, respectively. Both of these
      current changes were dependent on intracellular Ca2+ concentration and inhibited
      by niflumic acid and T16Ainh-A01. Quantitative real-time PCR, Western blotting,
      and immunocytochemical analyses revealed that TMEM16A and TMEM16B were highly
      expressed in pineal glands. siRNA knockdown of TMEM16A and/or TMEM16B showed that
      both channels contribute to ClCa currents in pinealocytes. Conversely, co
      expression of TMEM16A and TMEM16B channels or the expression of this tandem
      channel in HEK293 cells mimicked the electrophysiological characteristics of ClCa
      currents in pinealocytes. Moreover, bimolecular fluorescence complementation,
      FRET, and co-immunoprecipitation experiments suggested that TMEM16A and TMEM16B
      can form heteromeric channels, as well as homomeric channels. In conclusion,
      pineal ClCa channels are composed of TMEM16A and TMEM16B subunits, and these
      fluxes regulate melatonin secretion in pineal glands.

PMID- 29187603
TI  - Defining the distinct, intrinsic properties of the novel type I interferon,
      IFNepsilon.
AB  - The type I interferons (IFNs) are a family of cytokines with diverse biological
      activities, including antiviral, antiproliferative, and immunoregulatory
      functions. The discovery of the hormonally regulated, constitutively expressed
      IFNepsilon has suggested a function for IFNs in reproductive tract homeostasis
      and protection from infections, but its intrinsic activities are untested. We
      report here the expression, purification, and functional characterization of
      murine IFNepsilon (mIFNepsilon). Recombinant mIFNepsilon (rmIFNepsilon) exhibited
      an alpha-helical fold characteristic of type I IFNs and bound to IFNalpha/beta
      receptor 1 (IFNAR1) and IFNAR2, but, unusually, it had a preference for IFNAR1.
      Nevertheless, rmIFNepsilon induced typical type I IFN signaling activity,
      including STAT1 phosphorylation and activation of canonical type I IFN signaling
      reporters, demonstrating that it uses the JAK-STAT signaling pathway. We also
      found that rmIFNepsilon induces the activation of T, B, and NK cells and exhibits
      antiviral, antiproliferative, and antibacterial activities typical of type I
      IFNs, albeit with 100-1000-fold reduced potency compared with rmIFNalpha1 and
      rmIFNbeta. Surprisingly, although the type I IFNs generally do not display cross
      species activities, rmIFNepsilon exhibited high antiviral activity on human
      cells, suppressing HIV replication and inducing the expression of known HIV
      restriction factors in human lymphocytes. Our findings define the intrinsic
      properties of murine IFNepsilon, indicating that it distinctly interacts with
      IFNAR and elicits pathogen-suppressing activity with a potency enabling host
      defense but with limited toxicity, appropriate for a protein expressed
      constitutively in a sensitive mucosal site, such as the reproductive tract.

PMID- 29187604
TI  - An invasive herbivore structures plant competitive dynamics.
AB  - Species interactions are central to our understanding of ecological communities,
      but may change rapidly with the introduction of invasive species. Invasive
      species can alter species interactions and community dynamics directly by having
      larger detrimental effects on some species than others, or indirectly by changing
      the ways in which native species compete among themselves. We tested the direct
      and indirect effects of an invasive aphid herbivore on a native aphid species and
      two host milkweed species. The invasive aphid caused a 10-fold decrease in native
      aphid populations, and a 30% increase in plant mortality (direct effects). The
      invasive aphid also increased the strength of interspecific competition between
      the two native plant hosts (indirect effects). By investigating the role that
      indirect effects play in shaping species interactions in native communities, our
      study highlights an understudied component of species invasions.

PMID- 29187605
TI  - Predictability of bee community composition after floral removals differs by
      floral trait group.
AB  - Plant-bee visitor communities are complex networks. While studies show that
      deleting nodes alters network topology, predicting these changes in the field
      remains difficult. Here, a simple trait-based approach is tested for predicting
      bee community composition following disturbance. I selected six fields with mixed
      cover of flower species with shallow (open) and deep (tube) nectar access, and
      removed all flowers or flower heads of species of each trait in different plots
      paired with controls, then observed bee foraging and composition. I compared the
      bee community in each manipulated plot with bees on the same flower species in
      control plots. The bee morphospecies composition in manipulations with only tube
      flowers remaining was the same as that in the control plots, while the bee
      morphospecies on only open flowers were dissimilar from those in control plots.
      However, the proportion of short- and long-tongued bees on focal flowers did not
      differ between control and manipulated plots for either manipulation. So, bees
      within some functional groups are more strongly linked to their floral trait
      partners than others. And, it may be more fruitful to describe expected bee
      community compositions in terms of relative proportions of relevant ecological
      traits than species, particularly in species-diverse communities.

PMID- 29187606
TI  - Studying placebo effects in model organisms will help us understand them in
      humans.
AB  - The placebo effect is widely recognized but important questions remain, for
      example whether the capacity to respond to a placebo is an evolved, and
      potentially ubiquitous trait, or an unpredictable side effect of another evolved
      process. Understanding this will determine the degree to which the physiology
      underlying placebo effects might be manipulated or harnessed to optimize medical
      treatments. We argue that placebo effects are cases of phenotypic plasticity
      where once predictable cues are now unpredictable. Importantly, this explains why
      placebo-like effects are observed in less complex organisms such as worms and
      flies. Further, this indicates that such species present significant
      opportunities to test hypotheses that would be ethically or pragmatically
      impossible in humans. This paradigm also suggests that data informative of human
      placebo effects pre-exist in studies of model organisms.

PMID- 29187607
TI  - Interactions between cleaner-birds and ungulates are personality dependent.
AB  - While a growing body of literature explores the ecological implications of
      consistent individual variation in the behaviour of wildlife, few studies have
      looked at the reciprocal influences of personality within interspecific
      interactions, despite the potentially significant impacts on biodiversity. Here I
      used two species involved in cleaner-bird behaviour-black-billed magpies (Pica
      pica) and Rocky mountain elk (Cervus canadensis)-to show that the exhibition of
      mutualistic behaviour can depend on the personality of the individual involved. I
      recorded suites of correlated behaviours in both elk and magpies to derive
      personality gradients from 'shy' to 'bold', which I compared with observations of
      interspecific interactions. I measured each half of this mutualistic relationship
      separately. I found that bold elk were more likely to aggressively reject magpie
      landings, while shy elk allowed magpies to land and groom them. Contrastingly, I
      found it was bold magpies that were willing to risk landings, while shy magpies
      rarely attempted landings. These results show that the exhibition of
      interspecific behaviour is predicated on the personality of the individuals, and
      thus likely contributes to the selection and maintenance of personality variation
      within populations.

PMID- 29187608
TI  - Structural biomechanics determine spectral purity of bush-cricket calls.
AB  - Bush-crickets (Orthoptera: Tettigoniidae) generate sound using tegminal
      stridulation. Signalling effectiveness is affected by the widely varying acoustic
      parameters of temporal pattern, frequency and spectral purity (tonality). During
      stridulation, frequency multiplication occurs as a scraper on one wing scrapes
      across a file of sclerotized teeth on the other. The frequency with which these
      tooth-scraper interactions occur, along with radiating wing cell resonant
      properties, dictates both frequency and tonality in the call. Bush-cricket
      species produce calls ranging from resonant, tonal calls through to non-resonant,
      broadband signals. The differences are believed to result from differences in
      file tooth arrangement and wing radiators, but a systematic test of the
      structural causes of broadband or tonal calls is lacking. Using phylogenetically
      controlled structural equation models, we show that parameters of file tooth
      density and file length are the best-fitting predictors of tonality across 40
      bush-cricket species. Features of file morphology constrain the production of
      spectrally pure signals, but systematic distribution of teeth alone does not
      explain pure-tone sound production in this family.

PMID- 29187609
TI  - Associations between imprinted gene expression in the placenta, human fetal
      growth and preeclampsia.
AB  - Genomic imprinting is essential for normal placental and fetal growth. One theory
      to explain the evolution of imprinting is the kinship theory (KT), which predicts
      that genes that are paternally expressed will promote fetal growth, whereas
      maternally expressed genes will suppress growth. We investigated the expression
      of imprinted genes using microarray measurements of expression in term placentae.
      Correlations between birthweight and the expression levels of imprinted genes
      were more significant than for non-imprinted genes, but did not tend to be
      positive for paternally expressed genes and negative for maternally expressed
      genes. Imprinted genes were more dysregulated in preeclampsia (a disorder
      associated with placental insufficiency) than randomly selected genes, and we
      observed an excess of patterns of dysregulation in preeclampsia that would be
      expected to reduce nutrient allocation to the fetus, given the predictions of the
      KT. However, we found no evidence of coordinated regulation among these imprinted
      genes. A few imprinted genes have previously been shown to be associated with
      fetal growth and preeclampsia, and our results indicate that this is true for a
      broader set of imprinted genes.

PMID- 29187610
TI  - The new face of JEM.
AB  - We are excited to introduce a new design for JEM.

PMID- 29187611
TI  - Enhancing Memory Consolidation through Slow Oscillation and Spindle
      Synchronization.

PMID- 29187612
TI  - Exploring the Role of CaMKIV in Homeostatic Plasticity.

PMID- 29187613
TI  - Introducing a new look for JCB.

PMID- 29187614
TI  - Early-career researchers: an interview with Paloma Gonzalez Bellido.
AB  - Paloma Gonzalez Bellido is a Lecturer in the Department of Physiology,
      Development and Neuroscience at the University of Cambridge, where she
      investigates insect vision. She received her Bachelor's degree in Marine Biology
      from the University of Queensland, Australia, before moving to the University of
      Sheffield for her PhD with Mikko Juusola, which she completed in 2009. Paloma has
      been awarded a Cozzarelli Prize and her research has been recognised by the
      Society for Neuroethology and the Society for Experimental Biology.

PMID- 29187615
TI  - Learning to starve: impacts of food limitation beyond the stress period.
AB  - Starvation is common among wild animal populations, and many individuals
      experience repeated bouts of starvation over the course of their lives. Although
      much information has been gained through laboratory studies of acute starvation,
      little is known about how starvation affects an animal once food is again
      available (i.e. during the refeeding and recovery phases). Many animals exhibit a
      curious phenomenon - some seem to 'get better' at starving following exposure to
      one or more starvation events - by this we mean that they exhibit potentially
      adaptive responses, including reduced rates of mass loss, reduced metabolic
      rates, and lower costs of digestion. During subsequent refeedings they may also
      exhibit improved digestive efficiency and more rapid mass gain. Importantly,
      these responses can last until the next starvation bout or even be inherited and
      expressed in the subsequent generation. Currently, however, little is known about
      the molecular regulation and physiological mechanisms underlying these changes.
      Here, we identify areas of research that can fill in the most pressing knowledge
      gaps. In particular, we highlight how recently refined techniques (e.g. stable
      isotope tracers, quantitative magnetic resonance and thermal measurement) as well
      as next-generation sequencing approaches (e.g. RNA-seq, proteomics and holobiome
      sequencing) can address specific starvation-focused questions. We also describe
      outstanding unknowns ripe for future research regarding the timing and severity
      of starvation, and concerning the persistence of these responses and their
      interactions with other ecological stressors.

PMID- 29187616
TI  - The evolution of honey bee dance communication: a mechanistic perspective.
AB  - Honey bee dance has been intensively studied as a communication system, and yet
      we still know very little about the neurobiological mechanisms supporting how
      dances are produced and interpreted. Here, we discuss how new information on the
      functions of the central complex (CX) of the insect brain might shed some light
      on possible neural mechanisms of dance behaviour. We summarise the features of
      dance communication across the species of the genus Apis We then propose that
      neural mechanisms of orientation and spatial processing found to be supported by
      the CX may function in dance communication also, and that this mechanistic link
      could explain some specific features of the dance form. This is purely a
      hypothesis, but in proposing this hypothesis, and how it might be investigated,
      we hope to stimulate new mechanistic analyses of dance communication.

PMID- 29187617
TI  - Considerations on the role of olfactory input in avian navigation.
AB  - A large amount of data documents an important role of olfactory input in pigeon
      navigation, but the nature of this role is not entirely clear. The olfactory
      navigation hypothesis assumes that odors are carrying essential navigational
      information, yet some recent experiments support an activating role of odors.
      This led to an ongoing controversy. An important, often-neglected aspect of the
      findings on olfaction is that olfactory deprivation affects avian navigation only
      at unfamiliar sites. The orientation of anosmic birds at familiar sites remains
      an enigma; earlier assumptions that they would rely on familiar landmarks have
      been disproven by the home-oriented behavior of anosmic pigeons additionally
      deprived of object vision, which clearly indicated the use by the birds of non
      visual, non-olfactory cues. However, if odors activate the establishing and
      enlarging of the navigational 'map' and promote the integration of local values
      of navigational factors into this map, it seems possible that such a process
      needs to occur only once at a given site, when the birds are visiting this site
      for the first time. If that were the case, the birds could interpret the local
      factors correctly at any later visit and orient by them. This hypothesis could
      explain the oriented behavior of birds at familiar sites, and it could also help
      to reconcile some of the seemingly controversial findings reported in the
      literature, where the effect of olfactory deprivation was reported to differ
      considerably between the various pigeon lofts, possibly because of different
      training procedures.

PMID- 29187618
TI  - Control surfaces of aquatic vertebrates: active and passive design and function.
AB  - Aquatic vertebrates display a variety of control surfaces that are used for
      propulsion, stabilization, trim and maneuvering. Control surfaces include paired
      and median fins in fishes, and flippers and flukes in secondarily aquatic
      tetrapods. These structures initially evolved from embryonic fin folds in fishes
      and have been modified into complex control surfaces in derived aquatic
      tetrapods. Control surfaces function both actively and passively to produce
      torque about the center of mass by the generation of either lift or drag, or
      both, and thus produce vector forces to effect rectilinear locomotion, trim
      control and maneuvers. In addition to fins and flippers, there are other
      structures that act as control surfaces and enhance functionality. The entire
      body can act as a control surface and generate lift for stability in
      destabilizing flow regimes. Furthermore, control surfaces can undergo active
      shape change to enhance their performance, and a number of features act as
      secondary control structures: leading edge tubercles, wing-like canards, multiple
      fins in series, finlets, keels and trailing edge structures. These modifications
      to control surface design can alter flow to increase lift, reduce drag and
      enhance thrust in the case of propulsive fin-based systems in fishes and marine
      mammals, and are particularly interesting subjects for future research and
      application to engineered systems. Here, we review how modifications to control
      surfaces can alter flow and increase hydrodynamic performance.

PMID- 29187619
TI  - Photoreceptor signalling is sufficient to explain the detectability threshold of
      insect aerial pursuers.
AB  - An essential biological task for many flying insects is the detection of small,
      moving targets, such as when pursuing prey or conspecifics. Neural pathways
      underlying such 'target-detecting' behaviours have been investigated for their
      sensitivity and tuning properties (size, velocity). However, which stage of
      neuronal processing limits target detection is not yet known. Here, we
      investigated several skilled, aerial pursuers (males of four insect species),
      measuring the target-detection limit (signal-to-noise ratio) of light-adapted
      photoreceptors. We recorded intracellular responses to moving targets of varying
      size, extended well below the nominal resolution of single ommatidia. We found
      that the signal detection limit (2* photoreceptor noise) matches physiological or
      behavioural target-detection thresholds observed in each species. Thus, across a
      diverse range of flying insects, individual photoreceptor responses to changes in
      light intensity establish the sensitivity of the feature detection pathway,
      indicating later stages of processing are dedicated to feature tuning, tracking
      and selection.

PMID- 29187620
TI  - Ocellar structure is driven by the mode of locomotion and activity time in
      Myrmecia ants.
AB  - Insects have exquisitely adapted their compound eyes to suit the ambient light
      intensity in the different temporal niches they occupy. In addition to the
      compound eye, most flying insects have simple eyes known as ocelli, which assist
      in flight stabilisation, horizon detection and orientation. Among ants, typically
      the flying alates have ocelli while the pedestrian workers lack this structure.
      The Australian ant genus Myrmecia is one of the few ant genera in which both
      workers and alates have three ocellar lenses. Here, we studied the variation in
      the ocellar structure in four sympatric species of Myrmecia that are active at
      different times of the day. In addition, we took advantage of the walking and
      flying modes of locomotion in workers and males, respectively, to ask whether the
      type of movement influences the ocellar structure. We found that ants active in
      dim light had larger ocellar lenses and wider rhabdoms compared with those in
      bright-light conditions. In the ocellar rhabdoms of workers active in dim-light
      habitats, typically each retinula cell contributed microvilli in more than one
      direction, probably destroying polarisation sensitivity. The organisation of the
      ocellar retina in the day-active workers and the males suggests that in these
      animals some cells are sensitive to the pattern of polarised skylight. We found
      that the night-flying males had a tapetum that reflects light back to the
      rhabdom, increasing their optical sensitivity. We discuss the possible functions
      of ocelli to suit the different modes of locomotion and the discrete temporal
      niches that animals occupy.

PMID- 29187621
TI  - Flight metabolic rate of Locusta migratoria in relation to oxygen partial
      pressure in atmospheres of varying diffusivity and density.
AB  - Flying insects have the highest mass-specific metabolic rate of all animals.
      Oxygen is supplied to the flight muscles by a combination of diffusion and
      convection along the internal air-filled tubes of the tracheal system. This study
      measured maximum flight metabolic rate (FMR) during tethered flight in the
      migratory locust Locusta migratoria under varying oxygen partial pressure (PO2 )
      in background gas mixtures of nitrogen (N2), sulfur hexafluoride (SF6) and helium
      (He), to vary O2 diffusivity and gas mixture density independently. With N2 as
      the sole background gas (normodiffusive-normodense), mass-independent FMR
      averaged 132+/-19 mW g-0.75 at normoxia (PO2 =21 kPa), and was not limited by
      tracheal system conductance, because FMR did not increase in hyperoxia. However,
      FMR declined immediately with hypoxia, oxy-conforming nearly completely. Thus,
      the locust respiratory system is matched to maximum functional requirements, with
      little reserve capacity. With SF6 as the sole background gas (hypodiffusive
      hyperdense), the shape of the relationship between FMR and PO2  was similar to
      that in N2, except that FMR was generally lower (e.g. 24% lower at normoxia).
      This appeared to be due to increased density of the gas mixture rather than
      decreased O2 diffusivity, because hyperoxia did not reverse it. Normoxic FMR was
      not significantly different in He-SF6 (hyperdiffusive-normodense) compared with
      the N2 background gas, and likewise there was no significant difference between
      FMR in SF6-He (normodiffusive-hyperdense) compared with the SF6 background gas.
      The results indicate that convection, not diffusion, is the main mechanism of O2
      delivery to the flight muscle of the locust when demand is high.

PMID- 29187622
TI  - Swim bladder morphology changes with female reproductive state in the mouth
      brooding African cichlid Astatotilapia burtoni.
AB  - Mouth brooding is an extreme form of parental care in which the brooding parent
      carries the developing young in their buccal cavity for the duration of
      development. Brooding fish need to compensate for the brood weight on the
      anterior portion of their body. For fishes with a compartmentalized swim bladder,
      gas distribution between the chambers may aid in regulating buoyancy during
      brooding. To test this hypothesis, we took radiographs of Astatotilapia burtoni
      to compare the swim bladder morphology of gravid, mouth-brooding and recovering
      females. Following spawning, females carry developing fish in their buccal cavity
      for ~2 weeks, resulting in a larger and rounder anterior swim bladder
      compartment. Comparatively, the swim bladder of gravid females is long and
      cylindrical. Using small beads to mimic brood weight and its effects on female
      buoyancy, swim bladder changes were induced that resembled those observed during
      brooding. Immediately after releasing their fry, brooding females swim at a
      positive angle of attack but correct their swimming posture to normal within 5
      min, suggesting a rapid change in swim bladder gas distribution. These data
      provide new insights into how swim bladder morphology and swimming behavior
      change during mouth brooding, and suggest a compartmentalized swim bladder may be
      a morphological adaptation for mouth brooding.

PMID- 29187623
TI  - Skill not athleticism predicts individual variation in match performance of
      soccer players.
AB  - Just as evolutionary biologists endeavour to link phenotypes to fitness, sport
      scientists try to identify traits that determine athlete success. Both
      disciplines would benefit from collaboration, and to illustrate this, we used an
      analytical approach common to evolutionary biology to isolate the phenotypes that
      promote success in soccer, a complex activity of humans played in nearly every
      modern society. Using path analysis, we quantified the relationships among
      morphology, balance, skill, athleticism and performance of soccer players. We
      focused on performance in two complex motor activities: a simple game of soccer
      tennis (1 on 1), and a standard soccer match (11 on 11). In both contests,
      players with greater skill and balance were more likely to perform better.
      However, maximal athletic ability was not associated with success in a game. A
      social network analysis revealed that skill also predicted movement. The
      relationships between phenotypes and success during individual and team sports
      have potential implications for how selection acts on these phenotypes, in humans
      and other species, and thus should ultimately interest evolutionary biologists.
      Hence, we propose a field of evolutionary sports science that lies at the nexus
      of evolutionary biology and sports science. This would allow biologists to take
      advantage of the staggering quantity of data on performance in sporting events to
      answer evolutionary questions that are more difficult to answer for other
      species. In return, sports scientists could benefit from the theoretical
      framework developed to study natural selection in non-human species.

PMID- 29187624
TI  - Delayed behavioural shifts undermine the sustainability of social-ecological
      systems.
AB  - Natural habitat destruction and fragmentation generate a time-delayed loss of
      species and associated ecosystem services. As social-ecological systems (SESs)
      depend on a range of ecosystem services, lagged ecological dynamics may affect
      their long-term sustainability. Here, we investigate the role of consumption
      changes for sustainability, under a time-delayed ecological feedback on
      agricultural production. We use a stylized model that couples the dynamics of
      biodiversity, technology, human demography and compliance with a social norm
      prescribing sustainable consumption. Compliance with the sustainable norm reduces
      both the consumption footprint and the vulnerability of SESs to transient
      overshoot-and-collapse population crises. We show that the timing and interaction
      between social, demographic and ecological feedbacks govern the transient and
      long-term dynamics of the system. A sufficient level of social pressure (e.g.
      disapproval) applied on the unsustainable consumers leads to the stable
      coexistence of unsustainable and sustainable or mixed equilibria, where both
      defectors and conformers coexist. Under bistability conditions, increasing
      extinction debts reduces the resilience of the system, thus favouring abrupt
      regime shifts towards unsustainable pathways. Given recent evidence of large
      extinction debts, such results call for farsightedness and a better understanding
      of time delays when studying the sustainability of coupled SESs.

PMID- 29187625
TI  - Cooperative breeding influences the number and type of vocalizations in avian
      lineages.
AB  - Although communicative complexity is often predicted to correlate with social
      complexity in animal societies, few studies have employed large-scale comparative
      analyses to test whether socially complex species have more complex systems of
      communication. I tested this social complexity hypothesis in birds (Class: Aves)
      using the large amount of natural history information that describes both vocal
      repertoire and social system in these species. To do so, I marshalled data from
      primary and secondary records of avian vocal repertoires (n = 253), and for each
      of the species in the dataset I recorded the reported repertoire size and
      associated species information. Using phylogenetic comparative methods, I found
      that cooperative breeding was a strong and repeatable predictor of vocal
      repertoire size, while other social variables, e.g. group size and group
      stability, had little or no influence on repertoire size. Importantly, repertoire
      sizes expanded concurrently with the evolution of cooperative breeding,
      suggesting a direct link between these two traits. Cooperatively breeding species
      devoted significantly more of their repertoire to contact calls and alarm calls.
      Overall, these results therefore lend support to the hypothesis that social
      complexity via behavioural coordination leads to increases in vocal complexity.

PMID- 29187626
TI  - A load-based mechanism for inter-leg coordination in insects.
AB  - Animals rely on an adaptive coordination of legs during walking. However, which
      specific mechanisms underlie coordination during natural locomotion remains
      largely unknown. One hypothesis is that legs can be coordinated mechanically
      based on a transfer of body load from one leg to another. To test this
      hypothesis, we simultaneously recorded leg kinematics, ground reaction forces and
      muscle activity in freely walking stick insects (Carausius morosus). Based on
      torque calculations, we show that load sensors (campaniform sensilla) at the
      proximal leg joints are well suited to encode the unloading of the leg in
      individual steps. The unloading coincides with a switch from stance to swing
      muscle activity, consistent with a load reflex promoting the stance-to-swing
      transition. Moreover, a mechanical simulation reveals that the unloading can be
      ascribed to the loading of a specific neighbouring leg, making it exploitable for
      inter-leg coordination. We propose that mechanically mediated load-based
      coordination is used across insects analogously to mammals.

PMID- 29187627
TI  - Selective harvest focused on sexual signal traits can lead to extinction under
      directional environmental change.
AB  - Humans commonly harvest animals based on their expression of secondary sexual
      traits such as horns or antlers. This selective harvest is thought to have little
      effect on harvested populations because offtake rates are low and usually only
      the males are targeted. These arguments do not, however, take the relationship
      between secondary sexual trait expression and animal condition into account:
      there is increasing evidence that in many cases the degree of expression of such
      traits is correlated with an animal's overall well-being, which is partly
      determined by their genetic match to the environment. Using an individual-based
      model, we find that when there is directional environmental change, selective
      harvest of males with the largest secondary sexual traits can lead to extinction
      in otherwise resilient populations. When harvest is not selective, the males best
      suited to a new environment gain the majority of matings and beneficial alleles
      spread rapidly. When these best-adapted males are removed, however, their
      beneficial alleles are lost, leading to extinction. Given the current changes
      happening globally, these results suggest that trophy hunting and other cases of
      selective harvest (such as certain types of insect collection) should be managed
      with extreme care whenever populations are faced with changing conditions.

PMID- 29187628
TI  - The genetic basis and enigmatic origin of melanic polymorphism in pomarine skuas
      (Stercorarius pomarinus).
AB  - A key outstanding issue in adaptive evolution is the relationship between the
      genetics of intraspecific polymorphism and interspecific evolution. Here, we show
      that the pale/dark ventral plumage polymorphism that occurs in both the pomarine
      skua (Stercorarius pomarinus) and Arctic skua (S. parasiticus) is the result of
      convergent evolution at the same locus (MC1R), involving some of the same amino
      acid sites. The dark melanic MC1R allele in the pomarine skua is strongly
      divergent from the pale MC1R alleles. Whereas the dark allele is closely related
      to MC1R alleles in three species of great skua (S. skua, S. maccormicki, S.
      lonnbergi), the pale pomarine skua MC1R alleles present a star-like pattern in an
      intermediate position on the haplotype network, closer to alleles of the long
      tailed skua (S. longicaudus). Variation at other nuclear loci confirms a close
      relationship between the pomarine skua and the great skuas. The plumage
      polymorphism in pomarine skuas might have arisen in the common ancestor of
      pomarine and great skuas, only being retained in pomarine skuas. Alternatively,
      the pale and melanic MC1R alleles may have evolved independently in different
      lineages and been brought together in pomarine skuas by hybridization. In this
      case, introgression of a pale MC1R allele into the pomarine skua from another
      skua lineage is most likely. Our current data do not permit us to distinguish
      between these hypotheses, and assaying genome-wide variation holds much promise
      in this regard. Nevertheless, we have uncovered an intriguing example of a
      functionally important allele within one species that is shared across species.

PMID- 29187629
TI  - Testing differential use of payoff-biased social learning strategies in children
      and chimpanzees.
AB  - Various non-human animal species have been shown to exhibit behavioural
      traditions. Importantly, this research has been guided by what we know of human
      culture, and the question of whether animal cultures may be homologous or
      analogous to our own culture. In this paper, we assess whether models of human
      cultural transmission are relevant to understanding biological fundamentals by
      investigating whether accounts of human payoff-biased social learning are
      relevant to chimpanzees (Pan troglodytes). We submitted 4- and 5-year-old
      children (N = 90) and captive chimpanzees (N = 69) to a token-reward exchange
      task. The results revealed different forms of payoff-biased learning across
      species and contexts. Specifically, following personal and social exposure to
      different tokens, children's exchange behaviour was consistent with proportional
      imitation, where choice is affected by both prior personally acquired and
      socially demonstrated token-reward information. However, when the socially
      derived information regarding token value was novel, children's behaviour was
      consistent with proportional observation; paying attention to socially derived
      information and ignoring their prior personal experience. By contrast,
      chimpanzees' token choice was governed by their own prior experience only, with
      no effect of social demonstration on token choice, conforming to proportional
      reservation. We also find evidence for individual- and group-level differences in
      behaviour in both species. Despite the difference in payoff strategies used, both
      chimpanzees and children adopted beneficial traits when available. However, the
      strategies of the children are expected to be the most beneficial in promoting
      flexible behaviour by enabling existing behaviours to be updated or replaced with
      new and often superior ones.

PMID- 29187630
TI  - Evolutionary history of enigmatic bears in the Tibetan Plateau-Himalaya region
      and the identity of the yeti.
AB  - Although anecdotally associated with local bears (Ursus arctos and U.
      thibetanus), the exact identity of 'hominid'-like creatures important to folklore
      and mythology in the Tibetan Plateau-Himalaya region is still surrounded by
      mystery. Recently, two purported yeti samples from the Himalayas showed genetic
      affinity with an ancient polar bear, suggesting they may be from previously
      unrecognized, possibly hybrid, bear species, but this preliminary finding has
      been under question. We conducted a comprehensive genetic survey of field
      collected and museum specimens to explore their identity and ultimately infer the
      evolutionary history of bears in the region. Phylogenetic analyses of
      mitochondrial DNA sequences determined clade affinities of the purported yeti
      samples in this study, strongly supporting the biological basis of the yeti
      legend to be local, extant bears. Complete mitochondrial genomes were assembled
      for Himalayan brown bear (U. a. isabellinus) and black bear (U. t. laniger) for
      the first time. Our results demonstrate that the Himalayan brown bear is one of
      the first-branching clades within the brown bear lineage, while Tibetan brown
      bears diverged much later. The estimated times of divergence of the Tibetan
      Plateau and Himalayan bear lineages overlap with Middle to Late Pleistocene
      glaciation events, suggesting that extant bears in the region are likely
      descendants of populations that survived in local refugia during the Pleistocene
      glaciations.

PMID- 29187631
TI  - A signature of dynamic biogeography: enclaves indicate past species replacement.
AB  - Understanding how species have replaced each other in the past is important to
      predicting future species turnover. While past species replacement is difficult
      to detect after the fact, the process may be inferred from present-day
      distribution patterns. Species with abutting ranges sometimes show a
      characteristic distribution pattern, where a section of one species range is
      enveloped by that of the other. Such an enclave could indicate past species
      replacement: when a species is partly supplanted by a competitor, but a
      population endures locally while the invading species moves around and past it,
      an enclave forms. If the two species hybridize and backcross, the receding
      species is predicted to leave genetic traces within the expanding one under a
      scenario of species replacement. By screening dozens of genes in hybridizing
      crested newts, we uncover genetic remnants of the ancestral species, now
      inhabiting an enclave, in the range of the surrounding invading species. This
      independent genetic evidence supports the past distribution dynamics we predicted
      from the enclave. We suggest that enclaves provide a valuable tool in
      understanding historical species replacement, which is important because a major
      conservation concern arising from anthropogenic climate change is increased
      species replacement in the future.

PMID- 29187632
TI  - Selection bias in studies of human reproduction-longevity trade-offs.
AB  - A shorter lifespan as a potential cost of high reproductive effort in humans has
      intrigued researchers for more than a century. However, the results have been
      inconclusive so far and despite strong theoretical expectations we do not
      currently have compelling evidence for the longevity costs of reproduction. Using
      Monte Carlo simulation, it is shown here that a common practice in human
      reproduction-longevity studies using historical data (the most relevant data
      sources for this question), the omission of women who died prior to menopausal
      age from the analysis, results in severe underestimation of the potential
      underlying trade-off between reproduction and lifespan. In other words, assuming
      that such a trade-off is expressed also during reproductive years, the strength
      of the trade-off between reproduction and lifespan is progressively weakened when
      women dying during reproductive ages are sequentially and non-randomly excluded
      from the analysis. In cases of small sample sizes (e.g. few hundreds of
      observations), this selection bias by reducing statistical power may even partly
      explain the null results commonly found in this field. Future studies in this
      field should thus apply statistical approaches that account for or avoid
      selection bias in order to recover reliable effect size estimates between
      reproduction and longevity.

PMID- 29187633
TI  - Adversity magnifies the importance of social information in decision-making.
AB  - Decision-making theories explain animal behaviour, including human behaviour, as
      a response to estimations about the environment. In the case of collective
      behaviour, they have given quantitative predictions of how animals follow the
      majority option. However, they have so far failed to explain that in some species
      and contexts social cohesion increases when conditions become more adverse (i.e.
      individuals choose the majority option with higher probability when the estimated
      quality of all available options decreases). We have found that this failure is
      due to modelling simplifications that aided analysis, like low levels of
      stochasticity or the assumption that only one choice is the correct one. We
      provide a more general but simple geometric framework to describe optimal or
      suboptimal decisions in collectives that gives insight into three different
      mechanisms behind this effect. The three mechanisms have in common that the
      private information acts as a gain factor to social information: a decrease in
      the privately estimated quality of all available options increases the impact of
      social information, even when social information itself remains unchanged. This
      increase in the importance of social information makes it more likely that agents
      will follow the majority option. We show that these results quantitatively
      explain collective behaviour in fish and experiments of social influence in
      humans.

PMID- 29187634
TI  - Evidence-based controls for epidemics using spatio-temporal stochastic models in
      a Bayesian framework.
AB  - The control of highly infectious diseases of agricultural and plantation crops
      and livestock represents a key challenge in epidemiological and ecological
      modelling, with implemented control strategies often being controversial.
      Mathematical models, including the spatio-temporal stochastic models considered
      here, are playing an increasing role in the design of control as agencies seek to
      strengthen the evidence on which selected strategies are based. Here, we
      investigate a general approach to informing the choice of control strategies
      using spatio-temporal models within the Bayesian framework. We illustrate the
      approach for the case of strategies based on pre-emptive removal of individual
      hosts. For an exemplar model, using simulated data and historic data on an
      epidemic of Asiatic citrus canker in Florida, we assess a range of measures for
      prioritizing individuals for removal that take account of observations of an
      emerging epidemic. These measures are based on the potential infection hazard a
      host poses to susceptible individuals (hazard), the likelihood of infection of a
      host (risk) and a measure that combines both the hazard and risk (threat). We
      find that the threat measure typically leads to the most effective control
      strategies particularly for clustered epidemics when resources are scarce. The
      extension of the methods to a range of other settings is discussed. A key feature
      of the approach is the use of functional-model representations of the epidemic
      model to couple epidemic trajectories under different control strategies. This
      induces strong positive correlations between the epidemic outcomes under the
      respective controls, serving to reduce both the variance of the difference in
      outcomes and, consequently, the need for extensive simulation.

PMID- 29187635
TI  - Structural similarities in the CPC clip motif explain peptide-binding promiscuity
      between glycosaminoglycans and lipopolysaccharides.
AB  - Lipopolysaccharides (LPSs) and glycosaminoglycans (GAGs) are polymeric structures
      containing negatively charged disaccharide units that bind to specialized
      proteins and peptides in the human body and control fundamental processes such as
      inflammation and coagulation. Surprisingly, some proteins can bind both LPSs and
      GAGs with high affinity, suggesting that a cross-communication between these two
      pathways can occur. Here, we explore whether GAGs and LPSs can share common
      binding sites in proteins and what are the structural determinants of this
      binding. We found that the LPS-binding peptide YI12WF, derived from protein FhuA,
      can bind both heparin and E. coli LPS with high affinity. Most interestingly,
      mutations decreasing heparin binding in the peptide also reduce LPS affinity. We
      show that such mutations involve the CPC clip motif in the peptide, a small three
      dimensional signature required for heparin binding. Overall, we conclude that
      negatively charged polysaccharide-containing polymers such as GAGs and LPSs can
      compete for similar binding sites in proteins, and that the CPC clip motif is
      essential to bind both ligands. Our results provide a structural framework to
      explain why these polymers can cross-interact with the same proteins and peptides
      and thus contribute to the regulation of apparently unrelated processes in the
      body.

PMID- 29187636
TI  - Making sense of snapshot data: ergodic principle for clonal cell populations.
AB  - Population growth is often ignored when quantifying gene expression levels across
      clonal cell populations. We develop a framework for obtaining the molecule number
      distributions in an exponentially growing cell population taking into account its
      age structure. In the presence of generation time variability, the average
      acquired across a population snapshot does not obey the average of a dividing
      cell over time, apparently contradicting ergodicity between single cells and the
      population. Instead, we show that the variation observed across snapshots with
      known cell age is captured by cell histories, a single-cell measure obtained from
      tracking an arbitrary cell of the population back to the ancestor from which it
      originated. The correspondence between cells of known age in a population with
      their histories represents an ergodic principle that provides a new
      interpretation of population snapshot data. We illustrate the principle using
      analytical solutions of stochastic gene expression models in cell populations
      with arbitrary generation time distributions. We further elucidate that the
      principle breaks down for biochemical reactions that are under selection, such as
      the expression of genes conveying antibiotic resistance, which gives rise to an
      experimental criterion with which to probe selection on gene expression
      fluctuations.

PMID- 29187637
TI  - Mathematical modelling of microbes: metabolism, gene expression and growth.
AB  - The growth of microorganisms involves the conversion of nutrients in the
      environment into biomass, mostly proteins and other macromolecules. This
      conversion is accomplished by networks of biochemical reactions cutting across
      cellular functions, such as metabolism, gene expression, transport and
      signalling. Mathematical modelling is a powerful tool for gaining an
      understanding of the functioning of this large and complex system and the role
      played by individual constituents and mechanisms. This requires models of
      microbial growth that provide an integrated view of the reaction networks and
      bridge the scale from individual reactions to the growth of a population. In this
      review, we derive a general framework for the kinetic modelling of microbial
      growth from basic hypotheses about the underlying reaction systems. Moreover, we
      show that several families of approximate models presented in the literature,
      notably flux balance models and coarse-grained whole-cell models, can be derived
      with the help of additional simplifying hypotheses. This perspective clearly
      brings out how apparently quite different modelling approaches are related on a
      deeper level, and suggests directions for further research.

PMID- 29187638
TI  - Numb prevents a complete epithelial-mesenchymal transition by modulating Notch
      signalling.
AB  - Epithelial-mesenchymal transition (EMT) plays key roles during embryonic
      development, wound healing and cancer metastasis. Cells in a partial EMT or
      hybrid epithelial/mesenchymal (E/M) phenotype exhibit collective cell migration,
      forming clusters of circulating tumour cells-the primary drivers of metastasis.
      Activation of cell-cell signalling pathways such as Notch fosters a partial or
      complete EMT, yet the mechanisms enabling cluster formation remain poorly
      understood. Using an integrated computational-experimental approach, we examine
      the role of Numb-an inhibitor of Notch intercellular signalling-in mediating EMT
      and clusters formation. We show via an mathematical model that Numb inhibits a
      full EMT by stabilizing a hybrid E/M phenotype. Consistent with this observation,
      knockdown of Numb in stable hybrid E/M cells H1975 results in a full EMT, thereby
      showing that Numb acts as a brake for a full EMT and thus behaves as a
      'phenotypic stability factor' by modulating Notch-driven EMT. By generalizing the
      mathematical model to a multi-cell level, Numb is predicted to alter the balance
      of hybrid E/M versus mesenchymal cells in clusters, potentially resulting in a
      higher tumour-initiation ability. Finally, Numb correlates with a worse survival
      in multiple independent lung and ovarian cancer datasets, hence confirming its
      relationship with increased cancer aggressiveness.

PMID- 29187639
TI  - Identifying spatio-temporal dynamics of Ebola in Sierra Leone using virus
      genomes.
AB  - Containing the recent West African outbreak of Ebola virus (EBOV) required the
      deployment of substantial global resources. Despite recent progress in analysing
      and modelling EBOV epidemiological data, a complete characterization of the
      spatio-temporal spread of Ebola cases remains a challenge. In this work, we offer
      a novel perspective on the EBOV epidemic in Sierra Leone that uses individual
      virus genome sequences to inform population-level, spatial models. Calibrated to
      phylogenetic linkages of virus genomes, these spatial models provide unique
      insight into the disease mobility of EBOV in Sierra Leone without the need for
      human mobility data. Consistent with other investigations, our results show that
      the spread of EBOV during the beginning and middle portions of the epidemic
      strongly depended on the size of and distance between populations. Our
      phylodynamic analysis also revealed a change in model preference towards a
      spatial model with power-law characteristics in the latter portion of the
      epidemic, correlated with the timing of major intervention campaigns. More
      generally, we believe this framework, pairing molecular diagnostics with a
      dynamic model selection procedure, has the potential to be a powerful forecasting
      tool along with offering operationally relevant guidance for surveillance and
      sampling strategies during an epidemic.

PMID- 29187640
TI  - Generative models for network neuroscience: prospects and promise.
AB  - Network neuroscience is the emerging discipline concerned with investigating the
      complex patterns of interconnections found in neural systems, and identifying
      principles with which to understand them. Within this discipline, one
      particularly powerful approach is network generative modelling, in which wiring
      rules are algorithmically implemented to produce synthetic network architectures
      with the same properties as observed in empirical network data. Successful models
      can highlight the principles by which a network is organized and potentially
      uncover the mechanisms by which it grows and develops. Here, we review the
      prospects and promise of generative models for network neuroscience. We begin
      with a primer on network generative models, with a discussion of compressibility
      and predictability, and utility in intuiting mechanisms, followed by a short
      history on their use in network science, broadly. We then discuss generative
      models in practice and application, paying particular attention to the critical
      need for cross-validation. Next, we review generative models of biological neural
      networks, both at the cellular and large-scale level, and across a variety of
      species including Caenorhabditis elegans, Drosophila, mouse, rat, cat, macaque
      and human. We offer a careful treatment of a few relevant distinctions, including
      differences between generative models and null models, sufficiency and
      redundancy, inferring and claiming mechanism, and functional and structural
      connectivity. We close with a discussion of future directions, outlining exciting
      frontiers both in empirical data collection efforts as well as in method and
      theory development that, together, further the utility of the generative network
      modelling approach for network neuroscience.

PMID- 29187641
TI  - Vasopressin stimulates the proliferation and differentiation of red blood cell
      precursors and improves recovery from anemia.
AB  - Arginine vasopressin (AVP) made by hypothalamic neurons is released into the
      circulation to stimulate water resorption by the kidneys and restore water
      balance after blood loss. Patients who lack this antidiuretic hormone suffer from
      central diabetes insipidus. We observed that many of these patients were anemic
      and asked whether AVP might play a role in red blood cell (RBC) production. We
      found that all three AVP receptors are expressed in human and mouse hematopoietic
      stem and progenitor cells. The AVPR1B appears to play the most important role in
      regulating erythropoiesis in both human and mouse cells. AVP increases
      phosphorylation of signal transducer and activator of transcription 5, as
      erythropoietin (EPO) does. After sublethal irradiation, AVP-deficient Brattleboro
      rats showed delayed recovery of RBC numbers compared to control rats. In mouse
      models of anemia (induced by bleeding, irradiation, or increased destruction of
      circulating RBCs), AVP increased the number of circulating RBCs independently of
      EPO. In these models, AVP appears to jump-start peripheral blood cell
      replenishment until EPO can take over. We suggest that specific AVPR1B agonists
      might be used to induce fast RBC production after bleeding, drug toxicity, or
      chemotherapy.

PMID- 29187642
TI  - Irisin protects mitochondria function during pulmonary ischemia/reperfusion
      injury.
AB  - Limb remote ischemic preconditioning (RIPC) is an effective means of protection
      against ischemia/reperfusion (IR)-induced injury to multiple organs. Many studies
      are focused on identifying endocrine mechanisms that underlie the cross-talk
      between muscle and RIPC-mediated organ protection. We report that RIPC releases
      irisin, a myokine derived from the extracellular portion of fibronectin domain
      containing 5 protein (FNDC5) in skeletal muscle, to protect against injury to the
      lung. Human patients with neonatal respiratory distress syndrome show reduced
      concentrations of irisin in the serum and increased irisin concentrations in the
      bronchoalveolar lavage fluid, suggesting transfer of irisin from circulation to
      the lung under physiologic stress. In mice, application of brief periods of
      ischemia preconditioning stimulates release of irisin into circulation and
      transfer of irisin to the lung subjected to IR injury. Irisin, via lipid raft
      mediated endocytosis, enters alveolar cells and targets mitochondria. Interaction
      between irisin and mitochondrial uncoupling protein 2 (UCP2) allows for
      prevention of IR-induced oxidative stress and preservation of mitochondrial
      function. Animal model studies show that intravenous administration of exogenous
      irisin protects against IR-induced injury to the lung via improvement of
      mitochondrial function, whereas in UCP2-deficient mice or in the presence of a
      UCP2 inhibitor, the protective effect of irisin is compromised. These results
      demonstrate that irisin is a myokine that facilitates RIPC-mediated lung
      protection. Targeting the action of irisin in mitochondria presents a potential
      therapeutic intervention for pulmonary IR injury.

PMID- 29187644
TI  - Nanoparticle targeting to the endothelium during normothermic machine perfusion
      of human kidneys.
AB  - Ex vivo normothermic machine perfusion (NMP) is a new clinical strategy to assess
      and resuscitate organs likely to be declined for transplantation, thereby
      increasing the number of viable organs available. Short periods of NMP provide a
      window of opportunity to deliver therapeutics directly to the organ and, in
      particular, to the vascular endothelial cells (ECs) that constitute the first
      point of contact with the recipient's immune system. ECs are the primary targets
      of both ischemia-reperfusion injury and damage from preformed antidonor
      antibodies, and reduction of perioperative EC injury could have long-term
      benefits by reducing the intensity of the host's alloimmune response. Using NMP
      to administer therapeutics directly to the graft avoids many of the limitations
      associated with systemic drug delivery. We have previously shown that polymeric
      nanoparticles (NPs) can serve as depots for long-term drug release, but ensuring
      robust NP accumulation within a target cell type (graft ECs in this case) remains
      a fundamental challenge of nanomedicine. We show that surface conjugation of an
      anti-CD31 antibody enhances targeting of NPs to graft ECs of human kidneys
      undergoing NMP. Using a two-color quantitative microscopy approach, we
      demonstrate that targeting can enhance EC accumulation by about 5- to 10-fold or
      higher in discrete regions of the renal vasculature. In addition, our studies
      reveal that NPs can also nonspecifically accumulate within obstructed regions of
      the vasculature that are poorly perfused. These quantitative preclinical human
      studies demonstrate the therapeutic potential for targeted nanomedicines
      delivered during ex vivo NMP.

PMID- 29187647
TI  - News from the IAEA-Management of disused sources.

PMID- 29187643
TI  - Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid
      alpha-glucosidase.
AB  - Glycogen storage disease type II or Pompe disease is a severe neuromuscular
      disorder caused by mutations in the lysosomal enzyme, acid alpha-glucosidase
      (GAA), which result in pathological accumulation of glycogen throughout the body.
      Enzyme replacement therapy is available for Pompe disease; however, it has
      limited efficacy, has high immunogenicity, and fails to correct pathological
      glycogen accumulation in nervous tissue and skeletal muscle. Using bioinformatics
      analysis and protein engineering, we developed transgenes encoding GAA that could
      be expressed and secreted by hepatocytes. Then, we used adeno-associated virus
      (AAV) vectors optimized for hepatic expression to deliver the GAA transgenes to
      Gaa knockout (Gaa-/-) mice, a model of Pompe disease. Therapeutic gene transfer
      to the liver rescued glycogen accumulation in muscle and the central nervous
      system, and ameliorated cardiac hypertrophy as well as muscle and respiratory
      dysfunction in the Gaa-/- mice; mouse survival was also increased. Secretable GAA
      showed improved therapeutic efficacy and lower immunogenicity compared to
      nonengineered GAA. Scale-up to nonhuman primates, and modeling of GAA expression
      in primary human hepatocytes using hepatotropic AAV vectors, demonstrated the
      therapeutic potential of AAV vector-mediated liver expression of secretable GAA
      for treating pathological glycogen accumulation in multiple tissues in Pompe
      disease.

PMID- 29187648
TI  - AC signal characterization for optimization of a CMOS single-electron pump.
AB  - Pumping single electrons at a set rate is being widely pursued as an electrical
      current standard. Semiconductor charge pumps have been pursued in a variety of
      modes, including single gate ratchet, a variety of 2-gate ratchet pumps, and 2
      gate turnstiles. Whether pumping with one or two AC signals, lower error rates
      can result from better knowledge of the properties of the AC signal at the
      device. In this work, we operated a CMOS single-electron pump with a 2-gate
      ratchet style measurement and used the results to characterize and optimize our
      two AC signals. Fitting this data at various frequencies revealed both a
      difference in signal path length and attenuation between our two AC lines. Using
      this data, we corrected for the difference in signal path length and attenuation
      by applying an offset in both the phase and the amplitude at the signal
      generator. Operating the device as a turnstile while using the optimized
      parameters determined from the 2-gate ratchet measurement led to much flatter,
      more robust charge pumping plateaus. This method was useful in tuning our device
      up for optimal charge pumping, and may prove useful to the semiconductor quantum
      dot community to determine signal attenuation and path differences at the device.

PMID- 29187645
TI  - Single-cut genome editing restores dystrophin expression in a new mouse model of
      muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a severe, progressive muscle disease caused
      by mutations in the dystrophin gene. The majority of DMD mutations are deletions
      that prematurely terminate the dystrophin protein. Deletions of exon 50 of the
      dystrophin gene are among the most common single exon deletions causing DMD. Such
      mutations can be corrected by skipping exon 51, thereby restoring the dystrophin
      reading frame. Using clustered regularly interspaced short palindromic
      repeats/CRISPR-associated 9 (CRISPR/Cas9), we generated a DMD mouse model by
      deleting exon 50. These DeltaEx50 mice displayed severe muscle dysfunction, which
      was corrected by systemic delivery of adeno-associated virus encoding CRISPR/Cas9
      genome editing components. We optimized the method for dystrophin reading frame
      correction using a single guide RNA that created reframing mutations and allowed
      skipping of exon 51. In conjunction with muscle-specific expression of Cas9, this
      approach restored up to 90% of dystrophin protein expression throughout skeletal
      muscles and the heart of DeltaEx50 mice. This method of permanently bypassing DMD
      mutations using a single cut in genomic DNA represents a step toward clinical
      correction of DMD mutations and potentially those of other neuromuscular
      disorders.

PMID- 29187649
TI  - [IL-6 promotes gastric cancer cell proliferation and EMT through regulating miR
      152/PIK3R3 pathway].
AB  - OBJECTIVE: To explore the role of interleukin (IL)-6 in gastric cancer cells and
      the mechanisms.? Methods: Gastric cancer cells MGC-803 were treated with 50 ng/mL
      of recombinant IL-6 protein, and then cell viability and cell migration were
      detected by MTT assay and wound-healing assay, respectively. The mRNA and protein
      expressions of E-cadherin, N-cadherin, vimentin, Snail1 and miR-152 were analyzed
      by RT-qPCR and Western blot, respectively. Moreover, MGC-803 cells were
      simultaneously or separately treated with IL-6 and transfected with miR-152
      mimics, and then the mRNA expression of PIK3R3 and the protein levels of PIK3R3,
      Akt and p-Akt were determined.? Results: IL-6 stimulation significantly promoted
      cell proliferation and migration, reduced the expression of E-cadherin and miR
      152, and increased the expression of N-cadherin, vimentin, Snail1, PIK3R3 and p
      Akt (All P<0.05). The protein levels of PIK3R3 and p-Akt were significantly
      decreased after transfecting miR-152 mimics into MGC-803 cells (P<0.01). miR-152
      overexpression down-regulated IL-6-induced the protein expression of PIK3R3 and p
      Akt (P<0.01). The levels of Akt in each group were not changed.? Conclusion: IL-6
      up-regulates PIK3R3 expression and activates PI3K/Akt signaling pathway through
      down-regulating miR-152 expression, which consequently promotes gastric cancer
      cell proliferation, migration, and epithelial-mesenchymal transition.

PMID- 29187650
TI  - [Transhepatic arterial embolization with superparamagnetic iron oxide and
      lipiodol for the treatment of VX2 tumor in rabbits].
AB  - OBJECTIVE: To evaluate the feasibility and therapeutic efficacy of transhepatic
      arterial embolization with superparamagnetic iron oxide (SPIO) and lipiodol (LIP)
      for the treatment of VX2 tumor in rabbits.? Methods: Twenty-four rabbits with
      hepatic VX2 tumors by surgical implantation were randomly divided into 4 groups
      and treated with transhepatic arterial embolization of 4 different agents as
      follows (n=6 each): doxorubicin (DOX) group, DOX-LIP group, SPIO-DOX group, and
      SPIO-DOX-LIP group. Liver function (AST and ALT) was measured at 0, 1, 3, 5 and 7
      d after transhepatic arterial embolization. The serum DOX level was measured at
      0, 5, 15, 30, 60, and 120 minutes after transhepatic arterial embolization. MRI
      was performed at 7 d after the treatment to assess the distribution of SPIO in
      the SPIO-DOX group and SPIO-DOX-LIP group, while CT was performed to assess the
      distribution of LIP in the DOX-LIP group and SPIO-DOX-LIP group. All the rabbits
      were sacrificed and their livers were removed at 7 d after treatment for the
      detection of tissue DOX level. The histopathologic examinations were performed
      including HE staining, Prussian blue staining and TUNEL assay, and then the tumor
      necrosis percentage and apoptosis index were calculated.? Results: Compared to
      the DOX group, the levels of AST and ALT in other 3 groups were significantly
      elevated at 1 and 3 d after embolization (P<0.05). The levels of ALT and AST in
      the DOX group, DOX-LIP group or SPIO-DOX-LIP group returned to the baseline at
      day 7, there were no significant differences (P>0.05). The SPIO-DOX-LIP group
      exhibited the lowest serum DOX level at all time points up to 120 minutes after
      embolization (P<0.05). However, the tissue DOX level in the SPIO-DOX-LIP group
      was the highest among all groups at day 7 (P<0.05). The SPIO-DOX group and SPIO
      DOX-LIP group showed significantly lower MRI signal intensity of tumors in T2
      weighted imaging (T2WI) at day 7. Meanwhile DOX-LIP group and SPIO-DOX-LIP group
      showed that high-density lipiodol was deposited in the tumors in CT images.
      Histopathologic findings showed an almost complete central necrosis coagulation
      of tumors in the SPIO-DOX-LIP group, and the tumor necrosis percentage and tumor
      apoptosis index were significantly increased in the SPIO-DOX-LIP group compared
      to those in other 3 groups (P<0.05).? Conclusion: This novel drug-delivery system
      of SPIO nano-drug carrier together with LIP is safe and feasible when it is used
      for transhepatic arterial embolization for liver tumor. It provides an excellent
      MR and CT visualization and improves the therapeutic efficacy for the treatment
      of rabbit VX2 liver tumor.

PMID- 29187651
TI  - [Comparison of effects between IL-2 and IL-7 on glutamic acid decarboxylase 65
      reactive T cell responses in patients with Type 1 diabetes].
AB  - OBJECTIVE: To explore the type of cytokine (IL-2 or IL-7) and its most optimal
      concentration regarding the improvement of the signal-to-noise ratio of glutamic
      acid decarboxylase 65 (GAD65) in enzyme-linked immunospot (ELISPOT) assay in Type
      1 diabetic (T1DM) patients.? Methods: Twenty T1DM patients (Group A) and sixteen
      healthy controls matched with age and sex (Group B) were enrolled in our study,
      and their peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll
      method. GAD65, internal control and Pediacel served as "five-for-one" vaccine
      were selected as the stimulating antigen. Different concentrations of IL-2 [0
      U/mL (Group 1), 0.5 U/mL (Group 2), 2.5 U/mL (Group 3) and 12.5 U/mL (Group 4)]
      were added to the culture system. The CD4+ T cells of secreting interferon-gamma
      (IFN-gamma) in the above groups were determined by ELISPOT. The spots number, net
      values and stimulating index (SI) were compared in GAD65 (signal) and internal
      control (background). Next, another 21 T1DM patients (Group C)and 12 healthy
      controls matched with age and sex (Group D) were enrolled, and the specific T
      cell response to the GAD65 antigen was detected. The net values and SI were
      compared between the best optimal concentration of IL-2 (2.5 U/mL, Group 5) and
      IL-7 (0.5 ng/mL, Group 6).? Results: 1) After adding IL-2 into the Group A, the
      amount of GAD65 reactive T cells in different groups increased compared with
      Group A1, while the background in the internal control also increased gradually
      with the increased concentration of IL-2. There was no significant difference in
      net value (signal-noise) in the different concentration between the Group A3 and
      the Group A4 (P>0.05). The SI in the Group A3 (2.8), the highest one, was
      significantly higher than that in the Group B3 (1.3) (P<0.05). 2) Although the
      number of GAD65 spots in the Group C6 and the Group D6 were slightly higher than
      that in the Group C5 and the Group D5, respectively, the background in the Group
      C6 and the Group D6 also increased, without statistical significance (P>0.05).
      The mean net value spot and SI in the Group C5 (net value: 5.5; SI: 2.8) were
      both significantly higher than those in the Group C6 (net value: 4.3; SI: 1.8)
      (both P<0.05).? Conclusion: The concentration of 2.5 U/mL for IL-2 is proved to
      be the best optimal concentration for GAD65 specific T-cell responses in ELISPOT
      in patients with T1DM. IL-2 is much better than IL-7 in improvement of the SI in
      the ELISPOT.

PMID- 29187652
TI  - [Cordyceps sinensis protects HK2 cells from ischemia-reperfusion injury through
      Sirt1 pathway].
AB  - OBJECTIVE: To investigate the effects of Cordyceps sinensis (CS) on cellular
      apoptosis and Sirt1 expression in HK2 cells followed by ischemia-reperfusion
      (I/R).? Methods: HK2 cells were incubated with different concentrations of CS
      (10, 20, 40, 80, 160, 320 mg/L) for 24 hours, and the optimal concentration of CS
      was selected by measuring cell proliferation. The confluent HK2 cells were
      incubated with 0.01 MUmol/L antimycin A for 2 hours to induce ischemia in vitro,
      and then the reperfusion was achieved by incubating cells with glucose-replete
      complete growth medium for 24 hours. HK2 cells were divided into 4 groups: a
      control group, an I/R group, an I/R+CS (160 mg/L) group, and an I/R+CS (160
      mg/L)+Sirtinol (25 MUmol/L) group. Twenty-four hours later, total RNA and protein
      were collected. The cell proliferation was evaluated by MTT assay; the mRNA and
      protein expression of Sirt1 and the cleaved caspase-3 were measured by qRT-PCR
      and Western blot, respectively. The cellular apoptosis rate was determined by
      Annexin V-FITC/PI double staining and flow cytometry.? Results: Certain
      concentrations (10-160 mg/L) of CS did not show effect on the proliferation of
      HK2 cells (P>0.05), while 320 mg/L of CS inhibited cell proliferation
      significantly (P<0.01); compared with the control group, the mRNA and protein
      expressions of Sirt1 and the cleaved caspase-3 in the I/R group were up-regulated
      (P<0.01) and the apoptosis rate was extremely high; compared with the I/R group,
      CS significantly up-regulated Sirt1 mRNA and protein expression (P<0.01) while
      down-regulated cleaved caspase-3 mRNA and protein levels (P<0.01), and reduced
      apoptosis rate (P<0.05). The effects of CS were blocked in the presence of
      sirtinol, an inhibitor of CS.? Conclusion: CS protects HK2 cells from I/R injury
      through activation of Sirt1 pathway.

PMID- 29187653
TI  - [Investigation of status for vascular access in hemodialysis patients at Xiangya
      Hospital of Central South University].
AB  - OBJECTIVE: To investigate the status of vascular access in hemodialysis patients
      in our center.? Methods: The general information of hemodialysis patients and
      types and complications of vascular access at Xiangya Hospital of Central South
      University from April 2015 to April 2016, were retrospectively analyzed.?
      Results: Among 258 prevalent patients, 87.60% of them had arteriovenous fistula
      (AVF), while 12.40% showed tunneled cuffed catheter. Of the 61 incident patients,
      80.33% of them initiated dialysis with a non-tunneled and non-cuffed catheter,
      8.19% with an AVF, 9.84% with a tunneled cuffed catheter, and 1.64% with needle
      puncture. The types of AVF access included 76.55% of wrist radiocephalic fistula,
      7.08% of mid-forearm cephalic fistula, 11.06% of elbow brachiocephalic fistula,
      and 5.31% of antecubital fistula and transposed basilic fistula. Seventy-seven
      (34.07%) patients with AVF suffered complications and wherein aneurysms accounted
      for 24.34%.? Conclusion: In maintenance hemodialysis patients, autologous AVF is
      the prevalent vascular access. In the beginners for dialysis, non-tunneled and
      non-cuffed catheter are their choice. Additional efforts and incentives may be
      necessary to improve vascular access during the initiation of hemodialysis.

PMID- 29187654
TI  - [Analysis for the effect of different regimens on ocular myasthenia gravis in
      children].
AB  - OBJECTIVE: To evaluate the efficacy, recurrent risk factors and transferable
      ratio of treatments with 3 different regiments on children with systematic
      myasthenia gravis (MG).? Methods: The data of 104 children with ocular MG from
      June 2010 to March 2014 were collected from Department of Pediatric Neurology of
      Xiangya Hospital and they were retrospectively studied. The patients were divided
      into 3 groups: a methylprednisolone group (n=44), a prednisone group (n=48) and a
      bromine pyridostigmine group (n=12). Evaluative system from American MG
      foundation was used to evaluate the efficacy of treatment and the ratio of ocular
      MG transformed into systematic MG.? Results: The efficacy in the
      methylprednisolone group was better than that in the prednisone group, and both
      of them were better than that in the bromine pyridostigmine group (both
      P<0.05).Methylprednisolone, prednisone combined with bromine pyridostigmine could
      reach a better long-term efficacy in children with ocular MG. Early treatment
      with glucocorticoid could reduce clinical relapse.? Conclusion: A treatment with
      high-dose methylprednisolone pulse can improve early clinical remission in
      children with ocular MG. However, there is a similar efficacy in the long run of
      different glucocorticoid therapeutic regiments. A relatively order onset age,
      infection and thyroid dysfunction are recurrent risk factors in children with
      ocular MG.

PMID- 29187655
TI  - [Imaging measurement and clinical significance of the angle between the axis of
      pedicle and the plane of lamina in lower cervical vertebra].
AB  - OBJECTIVE: To explore the imaging measurement and clinical significance of the
      angle between the axis of pedicle and the plane of lamina in lower cervical
      vertebra.? Methods: Three dimensional reconstruction of CT scan was performed in
      30 patients with cervical deformity, and the angle between the axis of pedicle
      and the plane of lamina was measured with the specific reconstructed CT image of
      C3-C7.? Results: 1) The left and right transverse angle of C3-C7 between the axis
      of pedicle and the ipsilateral plane of lamina were 98.3 degrees +/-6.3 degrees ,
      98.0 degrees +/-5.1 degrees , 97.5 degrees +/-6.9 degrees , 95.1 degrees +/-5.0
      degrees , 85.8 degrees +/-5.4 degrees  and 96.7 degrees +/-8.2 degrees , 98.7
      degrees +/-7.1 degrees , 97.8 degrees +/-3.6 degrees , 93.2 degrees +/-6.2
      degrees , 86.8 degrees +/-5.7 degrees , respectively, which showed a gradual
      decreasing trend. Meanwhile the angle of C3-C6 was more than 90 degrees and C7
      was less than 90 degrees. In addition to C6 with C3 and C7 with other segments,
      the rest of the differences between the sections was not statistically
      significant (all P>0.05). 2) The left and right transverse angle of C3-C7 between
      the axis of pedicle and the pedicle of vertebral arch of lamina were 0.2 degrees
      +/-4.5 degrees , 1.2 degrees +/-7.2 degrees , -0.8 degrees +/-6.8 degrees , -3.3
      degrees +/-5.4 degrees , -14.7 degrees +/-4.0 degrees  and -1.6 degrees +/-5.4
      degrees , 1.9 degrees +/-4.6 degrees , -0.5 degrees +/-6.0 degrees , -4.6 degrees
      +/-5.3 degrees , -13.7 degrees +/-3.4 degrees , respectively, which showed a
      first increasing and then reducing trend. Meanwhile the angle of C4 was maximum
      angle. In addition to C6 with C3, C6 with C4, and C7 with other segments, the
      differences between the sections was not statistically significant (all P>0.05).
      3) The left and right sagittal angle of C3-C7 between the axis of pedicle and the
      ipsilateral plane of lamina were 77.7 degrees +/-7.6 degrees , 77.0 degrees +/
      7.1 degrees , 85.3 degrees +/-8.4 degrees , 94.1 degrees +/-2.2 degrees , 94.9
      degrees +/-3.8 degrees  and 78.5 degrees +/-7.1 degrees , 76.2 degrees +/-6.2
      degrees , 86.4 degrees +/-6.4 degrees , 94.0 degrees +/-2.7 degrees , 95.6
      degrees +/-3.8 degrees , respectively, which showed a gradual increasing trend.
      The angle of C3-C4 was less than 90 degrees. C5 showed large variation and C6-C7
      was more than 90 degrees. In addition to C3 with C4 and C6 with C7, the
      differences between the sections was statistically significant (all P<0.05).
      There was no significant difference between the two sides of the above indexes
      (all P>0.05).? Conclusion: In low cervical vertebra, there is a certain angle
      relationship between the axis of pedicle and the plane of lamina, which can
      provide reference for the clinical determination of angle of pedicle screw
      insertion.

PMID- 29187656
TI  - [Perioperative safety of Tibetan children with congenital heart disease
      undergoing cardiac surgery and anesthesia in low-altitude area].
AB  - OBJECTIVE: To observe the clinical parameters and short-term prognosis of Tibetan
      high-altitude area children with congenital heart disease undergoing surgery and
      anaesthesia in low-altitude area, and to investigate the perioperative safety of
      the treatment.? Methods: From January, 2016 to December, 2016, 14 children with
      congenital heart disease who underwent surgery were assigned into 2 groups (n=7
      each): the high-altitude area group (X group, children from Tibetan Autonomous
      Region) and the low-altitude area group (H group, children from Hunan Province).
      Echocardiography data, perioperative hemodynamic changes, postoperative recovery,
      complication and perioperative serum N terminal pro B type natriuretic peptide
      (NT-proBNP) levels were recorded.? Results: There were no significant differences
      in cardiac structure and function between the 2 groups, while the incidence of
      pulmonary hypertension in the X group was significantly higher than that in the H
      group (P<0.05). There were no significant differences in perioperative
      hemodynamics between the 2 groups (P>0.05), while the duration in ICU in the X
      group was longer than that in the H group and the serum NT-proBNP level in the X
      group was higher than that in the H group (P<0.05).? Conclusion: For children
      with congenital heart disease in Tibetan high-altitude area, undergoing surgery
      in low-altitude area contributes to a steady perioperative hemodynamics and helps
      to increase the perioperative safety. There may be a higher risk of postoperative
      cardiac dysfunction in Tibetan children than that in low-altitude area.

PMID- 29187657
TI  - [Based on empirical research: a preliminary study on application of the social
      aging scale for healthy people].
AB  - OBJECTIVE: To build a social aging scale for healthy people, and get the accuracy
      and feasibility of the scale to judge the aging of healthy people on the basis of
      the empirical research.? Methods: Stratified random sampling was conducted
      according to the nine different age groups, and the age-related social function
      information was collected for healthy people by using the scale, which was made
      in our own plant; the distribution of the score, the correlations between the
      score and age or telomere length were analyzed by statistical software.? Results:
      A total of 2 297 subjects were collected for the analysis. The ratio of male to
      female was 0.8:1. Social function of aging score was in the range of 3.00-12.90;
      aging score of personal ability was in the range of 1.00-4.45; aging score of
      social participation was in the range of 1.00-4.52; and aging score of
      organizational communication was in the range of 1.00-5.00. The correlation
      coefficient of aging scores with age was 0.696 (P<0.001). The result of telomere
      length showed that the relative telomere length was 1.056+/-0.261. The telomere
      length in different groups were significantly different (F=35.803, P<0.001). The
      telomere length was negatively correlated with aging (r=-0.964, P<0.001) and
      social function of aging (r=-0.857, P<0.001), respectively.? Conclusion: The
      scores of age-related social function, personal ability, social participation,
      and organizational communication are increased with age. The telomere length is
      negatively correlated to aging score. The scale is applicable to measure social
      function of aging, which can provide reference for evaluation of the
      comprehensive of aging.

PMID- 29187658
TI  - [Pregnancy complications among women with polycystic ovary syndrome in China: a
      Meta-analysis].
AB  - OBJECTIVE: To estimate the status of pregnancy complications among women with
      polycystic ovary syndrome (PCOS) through a systematic review of published
      literatures.? Methods: Systematic literature searches were conducted in PubMed,
      Web of Science, Medline, Embase, Cochrane Library, China National Knowledge
      Infrastructure (CNKI), Wanfang, Weipu and China Biology Medicine disc (CBMdisc),
      as well as the relevant articles published from inception to April 1st 2017,
      which reported the prevalence of pregnancy complications among women with PCOS.
      Random effective models were used to calculate pooled prevalence and 95%
      confidence intervals. The Newcastle-Ottawa Scale (NOS) was used to evaluate the
      quality of those included studies. Subgroup analyses were used to evaluate the
      influence of overweight/obesity and insulin resistance before pregnancy on the
      estimates of pregnancy complications among women with PCOS.? Results: Fifty-nine
      studies involving 13 378 PCOS women and 49 395 non-PCOS women were included.
      Among women with PCOS, pooled estimates were 20.26% for gestational diabetes
      mellitus, 13.94% for hypertensive disorder of pregnancy, 64.16% for caesarean
      section, 13.35% for preterm birth, 9.84% for macrosomia, 5.88% for low birth
      weight, 5.25% for early gestational age, 8.45% for late gestational age, 1.93%
      for neonatal malformations, 0.88% for perinatal mortality and 3.71% for neonatal
      asphyxia. And the estimates of gestational diabetes mellitus, hypertensive
      disorder of pregnancy, caesarean section, preterm birth, macrosomia and neonatal
      asphyxia among women with PCOS were significantly higher than those in women
      without PCOS (all P<0.05). Subgroup analysis showed the estimates of gestational
      diabetes mellitus, macrosomia and late gestational age among PCOS women who were
      overweight/obesity before pregnancy were significant higher than those among PCOS
      women with normal BMI (all P<0.05); and compared to PCOS women without insulin
      resistance prior to pregnancy, PCOS women with pre-pregnancy insulin resistance
      were at an increased risk for gestational diabetes mellitus, preterm birth and
      macrosomia (all P<0.05).? Conclusion: PCOS in pregnancy is associated with high
      rates of pregnancy complications. It is an important risk factor for pregnancy
      complications.

PMID- 29187659
TI  - [Research progress in DEAD-box family protein in cancer].
AB  - DEAD-box family protein is a kind of ATP dependent RNA helicase, which plays a
      critical role in RNA metabolism. The DEAD-box family proteins can affect cell
      proliferation, differentiation, and apoptosis through regulating the expression
      of oncogenes, tumor suppressor genes and tumor related signaling pathways. It
      plays the role in promoting or suppressing cancer.

PMID- 29187660
TI  - [NMDA receptor and its role in cardiovascular diseases].
AB  - Cardiovascular disease is the main threat to human health, which is one of the
      important causes of death in worldwide. N-methyl-D-aspartate receptor (NMDAR) is
      one of crucial ionic glutamate receptors. The physiology and pharmacology
      function of the composition of NMDAR are very complicated. Researches have shown
      that NMDAR with a high permeability to calcium and a unique feature of
      controlling numerous calcium-dependent processes. NMDAR affects the occurrence
      and development of cardiovascular disease such as hypertension, arrhythmia,
      myocardial infarction.

PMID- 29187661
TI  - [Inflammation-relevant mechanisms for postoperative cognitive dysfunction and the
      preventive strategy].
AB  - Postoperative cognitive dysfunction (POCD) is thought to be a mild cognitive
      disorder. It means that patients without cognitive diseases before surgery suffer
      from subtle changes in psychomotility, personality, social skills and cognitive
      function after the surgery. A decline in memory is the core characteristics of
      these symptoms. POCD is mainly seen in the elderly people following surgery. It
      can prolong hospital stay, reduce quality of life, increase mortality, and thus
      aggravate the burden of public health. It is urgent to take precautions to reduce
      the incidence. The precise mechanism of POCD remains unclear. Previous studies
      have shown that inflammation plays an important role in it. Sterile surgery can
      result in peripheral inflammation. Through several pathways, the signals from the
      peripheral immune response were sent to central system. Due to the individual
      difference, the degree of the central neuroinflammation was also heterogeneous.
      Some inflammations may lead to the occurrence of POCD. In order to prevent POCD,
      we should focus on the anti-inflammatory therapy.

PMID- 29187662
TI  - [Primary culture of human normal epithelial cells].
AB  - The traditional primary culture methods of human normal epithelial cells have
      disadvantages of low activity of cultured cells, the low cultivated rate and
      complicated operation. To solve these problems, researchers made many studies on
      culture process of human normal primary epithelial cell. In this paper, we mainly
      introduce some methods used in separation and purification of human normal
      epithelial cells, such as tissue separation method, enzyme digestion separation
      method, mechanical brushing method, red blood cell lysis method, percoll layered
      medium density gradient separation method. We also review some methods used in
      the culture and subculture, including serum-free medium combined with low mass
      fraction serum culture method, mouse tail collagen coating method, and glass
      culture bottle combined with plastic culture dish culture method. The biological
      characteristics of human normal epithelial cells, the methods of
      immunocytochemical staining, trypan blue exclusion are described. Moreover, the
      factors affecting the aseptic operation, the conditions of the extracellular
      environment, the conditions of the extracellular environment during culture, the
      number of differential adhesion, and the selection and dosage of additives are
      summarized.

PMID- 29187663
TI  - [New drug developments of snake venom polypeptides and progress].
AB  - The value of snake venom polypeptides in clinical application has drawn extensive
      attention, and the development of snake polypeptides into new drugs with anti
      tumor, anti-inflammatory, antithrombotic, analgesic or antihypertensive
      properties has become the recent research hotspot. With the rapid development of
      molecular biology and biotechnology, the mechanisms of snake venom polypeptides
      are also gradually clarified. Numerous studies have demonstrated that snake venom
      polypeptides exert their pharmacological effects by regulating ion channels, cell
      proliferation, apoptosis, intracellular signaling pathway, and expression of
      cytokine as well as binding to relevant active sites or receptors.

PMID- 29187664
TI  - [Clinical characteristics of hemichorea associated with non-ketotic hyperglycemia
      in 3 patients: case report and literature review].
AB  - OBJECTIVE: To investigate the pathophysiology, clinical manifestation and
      neuroimaging characteristics and therapeutic experiences for hemichore associated
      with non-ketotic hyperglycemia (HC-NH).? Methods: Clinical data of three patients
      with HC-NH from Xiangya Hospital, Central South University were analyzed
      retrospectively, and the related literature was reviewed.? Results: The core
      clinical features of HC-NH were characterized by acute/subacute onset of
      hemichorea with non-ketotic hyperglycemia in the elderly females. Radiologic
      findings associated with HC-NH were characterized by hyperattenuation on computed
      tomographic (CT) scans and hyperintensity on T1-weighted magnetic resonance
      imaging (MRI) at unilateral basal ganglion region. Blood glucose control was the
      foundation of treatment. Dopamine receptor antagonists and benzodiazepine
      sedative were helpful in controlling hemichorea. ? Conclusion: Hemichorea
      hemiballismus is a rare complication of nonketotic hyperglycaemia in elderly type
      2 diabetes. It is associated with contralateral striatal radiological abnormality
      and typically T1 hyperintensity on MRI. The pathophysiology of HC-NH is not
      clear. The prognosis of HC-NH is favorable. Antidiabetic drugs combined with
      dopamine receptor antagonists can effectively relieve the hemichorea symptoms.

PMID- 29187665
TI  - [A case report of subcutaneous panniculitis-like T cell lymphoma with fever and
      erythema on the body as the initial symptoms].
AB  - Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare form of
      peripheral alpha/beta T cell skin lymphoma that is localized primarily in the
      subcutaneous adipose tissues. It is characterized by single or multiple painful
      subcutaneous nodules or lumps, often affecting the limbs. The patient presented
      to the Department of Dermatology, Second Xiangya Hospital, Central South
      University, who suffered from intermittent fever and erythema on the body,
      finally was diagnosed as SPTCL after histopathological examinations for twice.

PMID- 29187666
TI  - Impact of Objective Malnutrition Status on the Clinical Outcomes in Patients With
      Peripheral Artery Disease Following Endovascular Therapy.
AB  - BACKGROUND: Peripheral artery disease (PAD) is an athero-occlusive disease and a
      known risk factor for cardiovascular events. The controlling nutritional status
      (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for
      evaluating malnutrition and are reportedly associated with poor clinical outcomes
      in patients with fatal diseases. However, the effect of malnutrition on the
      clinical outcomes in patients with PAD remains unclear.Methods and Results:We
      enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition
      was diagnosed by CONUT score and GNRI as in previous reports. During a median
      follow-up period of 1,071 days, there were 67 major adverse cardiovascular and
      leg events (MACLEs). The CONUT score- and GNRI-based malnutrition statuses were
      identified in 56% and 46% of the patients, respectively. Proportion of
      malnutrition increased with advancing Fontaine class. The multivariate Cox
      proportional hazard regression analysis demonstrated that both the CONUT score-
      and GNRI-based malnutrition status was an independent predictor of MACLEs. The
      Kaplan-Meier analysis demonstrated that the MACLE ratio increased with
      deteriorating malnutrition. Finally, the addition of the CONUT score or GNRI to
      the known risk factors significantly improved the net reclassification index and
      integrated discrimination index. CONCLUSIONS: Malnutrition was common and closely
      associated with the clinical outcomes in patients with PAD, indicating that it is
      a novel therapeutic target in the management of these patients.

PMID- 29187667
TI  - Strategy and Outcome of Catheter Ablation for Persistent Atrial Fibrillation -
      Impact of Progress in the Mapping and Ablation Technologies.
AB  - Pulmonary vein (PV) antrum isolation (PVAI) is effective in treating paroxysmal
      atrial fibrillation (AF) but is less so for persistent AF. A recent randomized
      study on the ablation strategies for persistent AF demonstrated that 2 common
      atrial substrate modifications, creation of linear lesions in the left atrium and
      ablation of complex fractionated electrogram sites, in addition to PVAI did not
      improve the outcome compared with stand-alone PVAI, suggesting the necessity of a
      more individualized, selective approach to persistent AF. There are emerging
      technologies, including high-resolution mapping with the use of multi-electrode
      catheter and auto mapping system and contact force (CF) guide ablation; the
      former allows rapid and accurate confirmation of the completeness of PVAI, and
      the latter enhances the achievement of durable ablation lesions more securely.
      Ablation for fibrotic area(s) has been proposed as a new approach for substrate
      modification, and high-resolution mapping is useful to define the area with low
      voltage electrograms, a surrogate marker for atrial fibrosis. Ablation for non-PV
      triggers in addition to PVAI improves the outcome of persistent AF. Further,
      durable isolation of the left atrial posterior wall may reduce AF recurrence.
      These ablation strategies with concomitant use of the emerging technologies are
      strongly expected to enhance the effectiveness of catheter ablation for
      persistent AF.

PMID- 29187668
TI  - Exploring Risk Factors of Patient Falls: A Retrospective Hospital Record Study in
      Japan.
AB  - Patient falls are common adverse medical events in hospitals. The objectives of
      this study were to clarify the factors of patient falls at hospitalization or
      transfer to another ward, which could be assumed that patients experience new
      environment. Patients who were hospitalized or transferred to another ward at a
      hospital in Japan, between January 14 and February 14, 2014 were included. We
      used a risk assessment sheet and applied stepwise regression analysis to identify
      factors of patient falls. We also investigated changes in patient conditions on
      the risk assessment sheet by the chi-square test. A total of 1,362 patients
      (53.2% female; mean age, 57.1 +/- 18.0 years) were eligible for analysis, and 38
      (2.8%) fell during the study period. The fallers were significantly older than
      the non-fallers (63.8 +/- 18.0 vs. 56.9 +/- 18.7 years, P = 0.03), but no
      significant difference was seen in sex (55.3% vs. 53.1% female). "History of
      falls", "Tubes inserted", "Need assistance/supervision for toileting" and
      "Excretion more than two times per night" were significantly related to patient
      falls (adjusted odds ratios [95% confidence interval]: 2.41 [1.05-5.53], 3.64
      [1.57-8.43], 4.52 [2.00-10.23] and 3.92 [1.38-11.09]). Among 30 fallers,
      "Overestimation or non-understanding of own physical abilities" was significantly
      more frequent after falls (30.0%) than before falls (6.7%, P = 0.02). The factors
      found in this study might be useful for identifying patients at higher risk of
      falls.

PMID- 29187669
TI  - Usefulness of the Combination of Tuberculin Skin Test and Interferon-Gamma
      Release Assay in Diagnosing Children with Tuberculosis.
AB  - Japan is still designated as a medium incidence country, worldwide. Although the
      definitive diagnosis of tuberculosis is made by detecting pathogen from tissue
      specimens, collecting those from children is physically difficult. Therefore, we
      must frequently depend on the results of tuberculin skin test (TST) or interferon
      gamma release assay (IGRA). However, the value of IGRA in diagnosing tuberculosis
      in infants remains unclear. We implemented TST and IGRA concurrently and examined
      the significance of combining these two tests by analyzing cases where
      conflicting results were evident from other tests. Subjects included 52 children
      (24 boys, 28 girls) age 15 years or younger (4.0 +/- 3.4 years) who visited our
      hospital for close examination after medical checkup for tuberculosis contact
      tracing. The children underwent TST, T-SPOT(r).TB, chest plain radiography, and
      chest computed tomography with a view to tuberculosis diagnosis during a 26
      months period from January 2013 to March 2015. T-SPOT results were positive in
      9/52 cases (17.3%), and TST results were positive in 12/52 cases (23.1%).
      Conflicting results were observed in 7/52 cases (13.5%), and all cases were
      treated as latent tuberculosis infection or incident cases of tuberculosis. The
      value of T-SPOT in tuberculosis diagnosis in children is still being established.
      However, there are a number of cases where conflicting results for T-SPOT and TST
      are indicated. Thus, it is currently desirable to use T-SPOT and TST
      concomitantly for children at an early age, especially for children below the age
      of 5 years, as a diagnostic measure in complementing other techniques.

PMID- 29187670
TI  - Differential Development of Facial and Hind Paw Allodynia in a Nitroglycerin
      Induced Mouse Model of Chronic Migraine: Role of Capsaicin Sensitive Primary
      Afferents.
AB  - Despite the relatively high prevalence of migraine or headache, the
      pathophysiological mechanisms triggering headache-associated peripheral
      hypersensitivities, are unknown. Since nitric oxide (NO) is well known as a
      causative factor in the pathogenesis of migraine or migraine-associated
      hypersensitivities, a mouse model has been established using systemic
      administration of the NO donor, nitroglycerin (NTG). Here we tried to investigate
      the time course development of facial or hindpaw hypersensitivity after
      repetitive NTG injection. NTG (10 mg/kg) was administrated to mice every other
      day for nine days. Two hours post-injection, NTG produced acute mechanical and
      heat hypersensitivity in the hind paws. By contrast, cold allodynia, but not
      mechanical hypersensitivity, occurred in the facial region. Moreover, this
      hindpaws mechanical hypersensitivity and the facial cold allodynia was
      progressive and long-lasting. We subsequently examined whether the depletion of
      capsaicin-sensitive primary afferents (CSPAs) with resiniferatoxin (RTX, 0.02
      mg/kg) altered these peripheral hypersensitivities in NTG-treated mice. RTX
      pretreatment did not affect the NTG-induced mechanical allodynia in the hind paws
      nor the cold allodynia in the facial region, but it did inhibit the development
      of hind paw heat hyperalgesia. Similarly, NTG injection produced significant
      hindpaw mechanical allodynia or facial cold allodynia, but not heat hyperalgesia
      in transient receptor potential type V1 (TRPV1) knockout mice. These findings
      demonstrate that different peripheral hypersensitivities develop in the face
      versus hindpaw regions in a mouse model of repetitive NTG-induced migraine, and
      that these hindpaw mechanical hypersensitivity and facial cold allodynia are not
      mediated by the activation of CSPAs.

PMID- 29187671
TI  - Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in
      HepG2 Cells.
AB  - As a traditional herbal medicine, the fruits of Psoralea corylifolia L. (Fructus
      Psoraleae (FP)) have been widely used for the treatment of various skin diseases
      for hundred years. Recently, the emerging FP-induced toxic effects, especially
      hepatotoxicity, in clinic are getting the public's attention. However, its exact
      toxic components and mechanisms underlying remain unclear. Bavachin, one of
      flavonoids in FP, has been documented as a hepatotoxic substance, and the present
      study aimed to determine the toxicity caused by bavachin and the possible toxic
      mechanisms involved using human hepatocellular carcinoma (HepG2) cells. Our
      results showed that bavachin could significantly inhibited cell proliferation and
      trigger the endoplasmic reticulum (ER) stress in a dose dependent manner.
      Downregulating ER stress using tauroursodeoxycholic acid (TUDCA) obvious
      attenuated bavachin-triggerd cell apoptosis. Then, small interfering RNA (siRNA)
      knock-down of Mitofusion2 (Mfn2) resulted in a remarkable aggravation of ER
      stress through the inhibition of the phosphorylation of protein kinase B (Akt).
      Additionally, suppression of reactive oxygen species (ROS) by ROS Scavenger (N
      acetyl-l-cystein (NAC)) also reduced bavachin-induced ER stress. Taken together,
      our study demonstrated that bavachin-induced ER stress caused cell apoptosis by
      Mfn2-Akt pathway, and that ROS may participate upstream in this mechanism. Here,
      we not only provide a new understanding of ROS/Mfn2/Akt pathway in bavachin
      induced cytotoxicity via the ER stress, but also identify a new specific
      intervention to prevent FP-induced hepatotoxicity in the future.

PMID- 29187672
TI  - Clinical Characteristics and Low Susceptibility to Daptomycin in Enterococcus
      faecium Bacteremia.
AB  - Enterococcus faecium has high levels of resistance to multiple antibiotics, and
      the mortality due to E. faecium bacteremia is high. Accordingly, E. faecium
      strains with low susceptibility to daptomycin are a concern in clinical practice.
      This study assessed the predictive factors and prognosis of patients with
      bacteremia due to E. faecium as well as the antimicrobial susceptibility,
      particularly to daptomycin, among E. faecium isolates. The medical records of
      patients admitted to Osaka City University Hospital with E. faecalis (n = 60) and
      E. faecium (n = 48) bacteremia between January 2011 and March 2016 were
      retrospectively reviewed. The E. faecalis group (mean age: 62.0 years) included
      22 women, and the E. faecium group (mean age: 59.1 years) included 19 women.
      Predictive factors for infection, prognosis, and isolate antimicrobial
      susceptibilities were evaluated. The mean Sequential Organ Failure Assessment
      score and mortality rate did not differ between the two groups. The independent
      predictors of E. faecium bacteremia in multivariate analysis included quinolone
      use (p = 0.025), malignancy (p = 0.021), and prolonged hospitalization (p =
      0.016). Cardiovascular disease was associated with a reduced risk of E. faecium
      bacteremia (p = 0.015). Notably, the percentage of E. faecium isolates with low
      daptomycin susceptibility was higher than that of E. faecalis (8.5% vs. 0%, p =
      0.036). Thus, E. faecium should be considered when administering antibiotic
      therapy to patients with a history of these predictors. Furthermore, the use of
      daptomycin should be avoided in case of E. faecium with low susceptibility to
      daptomycin.

PMID- 29187673
TI  - Dietary interventions to prevent and manage diabetes in worksite settings: a meta
      analysis.
AB  - OBJECTIVES: The translation of lifestyle intervention to improve glucose
      tolerance into the workplace has been rare. The objective of this meta-analysis
      is to summarize the evidence for the effectiveness of dietary interventions in
      worksite settings on lowering blood sugar levels. METHODS: We searched for
      studies in PubMed, Embase, Econlit, Ovid, Cochrane, Web of Science, and
      Cumulative Index to Nursing and Allied Health Literature. Search terms were as
      follows: (1) Exposure-based: nutrition/diet/dietary intervention/health
      promotion/primary prevention/health behavior/health education/food /program
      evaluation; (2) Outcome-based: diabetes/hyperglycemia/glucose/HbA1c/glycated
      hemoglobin; and (3) Setting-based:
      workplace/worksite/occupational/industry/job/employee. We manually searched
      review articles and reference lists of articles identified from 1969 to December
      2016. We tested for between-studies heterogeneity and calculated the pooled
      effect sizes for changes in HbA1c (%) and fasting glucose (mg/dl) using random
      effect models for meta-analysis in 2016. RESULTS: A total of 17 articles out of
      1663 initially selected articles were included in the meta-analysis. With a
      random-effects model, worksite dietary interventions led to a pooled -0.18% (95%
      CI, -0.29 to -0.06; P<0.001) difference in HbA1c. With the random-effects model,
      the interventions resulted in 2.60 mg/dl lower fasting glucose with borderline
      significance (95% CI: -5.27 to 0.08, P=0.06). In the multivariate meta-regression
      model, the interventions with high percent of female participants and that used
      the intervention directly delivered to individuals, rather the environment
      changes, were associated with more effective interventions. CONCLUSION: Workplace
      dietary interventions can improve HbA1c. The effects were larger for the
      interventions with greater number of female participants and with individual
      level interventions.

PMID- 29187675
TI  - Scientific base for the Japanese Stress Check Program.

PMID- 29187674
TI  - Nitrative DNA damage in cultured macrophages exposed to indium oxide.
AB  - OBJECTIVES: Indium compounds are used in manufacturing displays of mobile phones
      and televisions. However, these materials cause interstitial pneumonia in exposed
      workers. Animal experiments demonstrated that indium compounds caused lung
      cancer. Chronic inflammation is considered to play a role in lung carcinogenesis
      and fibrosis induced by particulate matters. 8-Nitroguanine (8-nitroG) is a
      mutagenic DNA lesion formed during inflammation and may participate in
      carcinogenesis. To clarify the mechanism of carcinogenesis, we examined 8-nitroG
      formation in indium-exposed cultured cells. METHODS: We treated RAW 264.7 mouse
      macrophages with indium oxide (In2O3) nanoparticles (primary diameter: 30-50 nm),
      and performed fluorescent immunocytochemistry to detect 8-nitroG. The extent of 8
      nitroG formation was evaluated by quantitative image analysis. We measured the
      amount of nitric oxide (NO) in the culture supernatant of In2O3-treated cells by
      the Griess method. We also examined the effects of inhibitors of inducible NO
      synthase (iNOS) and endocytosis on In2O3-induced 8-nitroG formation. RESULTS:
      In2O3 significantly increased the intensity of 8-nitroG formation in RAW 264.7
      cells in a dose-dependent manner. In2O3-induced 8-nitroG formation was observed
      at 2 h and further increased at 4 h, and the amount of NO released from In2O3
      exposed cells was significantly increased at 2-4 h compared with the control. 8
      NitroG formation was suppressed by 1400W (an iNOS inhibitor), methyl-beta
      cyclodextrin and monodansylcadaverine (inhibitors of caveolae- and clathrin
      mediated endocytosis, respectively). CONCLUSIONS: These results suggest that
      endocytosis and NO generation participate in indium-induced 8-nitroG formation.
      NO released from indium-exposed inflammatory cells may induce DNA damage in
      adjacent lung epithelial cells and contribute to carcinogenesis.

PMID- 29187676
TI  - Three-Channeled Aortic Dissection in a Patient without Marfan Syndrome.
AB  - A 64-year-old man was admitted for evaluation of back pain. He did not have a
      Marfan syndrome (MFS)-like appearance, and had a history of a type B aortic
      dissection and total arch replacement. A connective tissue disorder had been
      suspected because of the histologic findings of the resected aortic wall. On
      admission, a computed tomography (CT) scan demonstrated a three-channeled aortic
      dissection (3ch-AD) measuring 63 mm in diameter. We planned to perform elective
      surgery during his hospitalization. On the fourth hospital day, he complained of
      severe back pain, and enhanced CT scan revealed an aortic rupture. The patients
      with 3ch-AD often have MFS. However, even if they do not have an MFS-like
      appearance, clinicians should consider fragility of the aortic wall in patients
      with 3ch-AD. If the aortic diameter is enlarged, early surgery is recommended. In
      particular, if a connective tissue disorder is obvious or suspected, emergent
      surgery is warranted.

PMID- 29187677
TI  - Prevention of Kinked Stent Graft Limb Due to Severe Angulated Proximal Neck
      during Endovascular Repair for Abdominal Aortic Aneurysm.
AB  - Although the technology of endovascular aortic repair (EVAR) for abdominal aortic
      aneurysm (AAA) is evolving that make it appealing for challenging anatomy,
      proximal aortic neck morphology, especially severe angulation, is still one of
      the most determinants for a successful procedure. We describe a patient of AAA
      with severely angulated proximal neck, in whom kinked stent graft limb occurred
      against severe angulation of proximal neck. Then, we suggested how to prevent
      this complication in the second patient. Our case demonstrated the stent graft
      limb could be kinked by severe aortic neck angulation, making it challenging.
      However, the kinked stent graft limb could be prevented by deploying stent graft
      limbs below the most severely angulated aortic neck intentionally.

PMID- 29187678
TI  - Additive Value of 3T 3D CISS Imaging to Conventional MRI for Assessing the
      Abnormal Vessels of Spinal Dural Arteriovenous Fistulae.
AB  - INTRODUCTION: We investigated the additive value of the 3T 3D constructive
      interference in steady state (CISS) sequence to conventional MRI for the
      evaluation of spinal dural arteriovenous fistulae (SDAVF). MATERIALS AND METHODS:
      We included 16 consecutive patients (15 men, 1 woman; age range 42-81 years; mean
      64 years) with SDAVF who underwent 3T MRI and digital subtraction angiography
      (DSA) before treatment. Two neuroradiologists independently evaluated the
      presence of abnormal vessels on 3D CISS-, T2- and T1-weighted images (T1WI,
      T2WI), and contrast-enhanced T1WI using a 3-point grading system. Interobserver
      agreement was assessed by calculating the kappa coefficient. RESULTS: The SDAVF
      site was the cervical region in one patient, the thoracic region in 12 patients,
      the lumbar region in two, and the sacral region in one. For the visualization of
      abnormal vessels, the mean score was significantly higher for 3D CISS than the
      other sequences (P < 0.05). In 12 of 16 cases (75%) both readers made definite
      positive findings on additional 3D-CISS images. Interobserver agreement was
      excellent for 3D CISS images (kappa = 1.0), good for T1WI (kappa = 0.78; 95%
      confidence interval [CI] 0.54-1.00) and T2WI (kappa = 0.74; 95% CI 0.48-1.00) and
      moderate for contrast-enhanced T1WI (CET1WI) (kappa = 0.50; 95% CI 0.21-0.80).
      CONCLUSION: For the assessment of abnormal vessels of SDAVF, the 3T 3D CISS
      sequence adds value to conventional MRI.

PMID- 29187679
TI  - Cardiac-driven Pulsatile Motion of Intracranial Cerebrospinal Fluid Visualized
      Based on a Correlation Mapping Technique.
AB  - PURPOSE: A correlation mapping technique delineating delay time and maximum
      correlation for characterizing pulsatile cerebrospinal fluid (CSF) propagation
      was proposed. After proofing its technical concept, this technique was applied to
      healthy volunteers and idiopathic normal pressure hydrocephalus (iNPH) patients.
      METHODS: A time-resolved three dimensional-phase contrast (3D-PC) sampled the
      cardiac-driven CSF velocity at 32 temporal points per cardiac period at each
      spatial location using retrospective cardiac gating. The proposed technique
      visualized distributions of propagation delay and correlation coefficient of the
      PC-based CSF velocity waveform with reference to a waveform at a particular point
      in the CSF space. The delay time was obtained as the amount of time-shift, giving
      the maximum correlation for the velocity waveform at an arbitrary location with
      that at the reference location. The validity and accuracy of the technique were
      confirmed in a flow phantom equipped with a cardiovascular pump. The technique
      was then applied to evaluate the intracranial CSF motions in young, healthy (N =
      13), and elderly, healthy (N = 13) volunteers and iNPH patients (N = 13).
      RESULTS: The phantom study demonstrated that root mean square error of the delay
      time was 2.27%, which was less than the temporal resolution of PC measurement
      used in this study (3.13% of a cardiac cycle). The human studies showed a
      significant difference (P < 0.01) in the mean correlation coefficient between the
      young, healthy group and the other two groups. A significant difference (P <
      0.05) was also recognized in standard deviation of the correlation coefficients
      in intracranial CSF space among all groups. The result suggests that the CSF
      space compliance of iNPH patients was lower than that of healthy volunteers.
      CONCLUSION: The correlation mapping technique allowed us to visualize pulsatile
      CSF velocity wave propagations as still images. The technique may help to
      classify diseases related to CSF dynamics, such as iNPH.

PMID- 29187680
TI  - Purification and characterization of a novel alpha-D-glucosidase from
      Lactobacillus fermentum with unique substrate specificity towards resistant
      starch.
AB  - Resistant starch is not digestible in the small intestine and is fermented by
      lactic acid bacteria in the large intestine into short chain fatty acids, such as
      acetate, propionate and butyrate, which result in several health benefits in
      analogy with dietary fibre components. The mode and mechanism of resistant starch
      degradation by lactic acid bacteria is still not understood. In the present
      study, we have purified alpha-D-glucosidase from Lactobacillus fermentum NCDC 156
      by employing three sequential steps i.e. ultra filtration, DEAE-cellulose and
      Sephadex G-100 chromatographies. It was found to be a monomeric protein (~50
      kDa). The optimum pH and temperature of this enzyme were found to be 5.5 and 37
      degrees C, respectively. Under optimised conditions with p-nitrophenyl-D
      glucopyranoside as the substrate, the enzyme exhibited a Km of 0.97 mM. Its
      activity was inhibited by Hg2+ and oxalic acid. N-terminal blocked purified
      enzyme was subjected to lysyl endopeptidase digestion and the resultant peptides
      were subjected to BLAST analysis to understand their homology with other alpha-D
      glucosidases from lactobacillus species.

PMID- 29187681
TI  - Identification of YbhA as the pyridoxal 5'-phosphate (PLP) phosphatase in
      Escherichia coli: Importance of PLP homeostasis on the bacterial growth.
AB  - The gene ybhA of Escherichia coli encodes a phosphatase that has an in vitro
      specificity to dephosphorylate pyridoxal 5'-phosphate (PLP or vitamin B6), a co
      factor for aminotransferases and other enzymes. In this study, we found that
      excess pyridoxal (PL) in a minimal medium resulted in excess PLP in vivo and
      growth inhibition, which was alleviated by YbhA overproduction. Conversely, the
      YbhA overproduction resulted in PLP shortage in vivo and the correlated reduction
      in growth rate, which was significantly negated by PL in the medium. In addition,
      the overproduction of a PL kinase, PdxK or PdxY, was inhibitory to cell growth
      only in the absence of the functional ybhA gene, and the growth defects were
      alleviated by casamino acids in the medium, which suggested that both the
      shortage of, and excess, PLP resulted in the disturbance of amino acid metabolism
      and cell growth, as revealed by a metabolome analysis.

PMID- 29187682
TI  - Bacterial glycerol oxidation coupled to sulfate reduction at neutral and acidic
      pH.
AB  - Glycerol is a main co-product of biodiesel production. Crude glycerol may serve
      as a cheap and attractive substrate in biotechnological applications, e.g. for
      the production of valuable chemicals or as an electron donor for reduction
      processes. In this work, sulfate reduction with glycerol was studied at neutral
      and acidic pH using bioreactor sludge samples and Tinto River sediments as a
      source of inoculum, respectively. Communities of sulfate-reducing bacteria (SRB)
      and fermentative bacteria were co-enriched at both pH values. Molecular analyses
      revealed that sequences belonging to Desulfomicrobium genus were dominant in the
      cultures enriched at pH 7, while Desulfosporosinus sequences dominated in the
      culture enriched at pH 4. Glycerol conversion was coupled to sulfate reduction,
      but the substrate was incompletely oxidized to acetate in the neutrophilic
      enrichments, and acetate, lactate, and 1,3-propanediol under low pH conditions.
      Two strains belonging to Desulfomicrobium and Proteiniphilum genera were isolated
      from the neutrophilic enrichments, but the first isolate was not able to use
      glycerol, which suggests a syntrophic relationship between glycerol-degrading
      fermentative bacteria and SRB. A Clostridium strain able to grow with glycerol
      was isolated from the low pH enrichment. Our data indicate that glycerol promotes
      the growth of sulfate-reducing communities to form sulfide, which can be used to
      precipitate and recover heavy metals.

PMID- 29187683
TI  - [Efficacy of high-dose steroid pulse therapy for anti-galactocerebroside antibody
      positive combined central and peripheral demyelination].
AB  - A 59-year-old man had been admitted to another hospital because of diplopia and
      thirst at the beginning of March and was diagnosed with diabetic ketoacidosis. He
      was referred to our hospital because he had limb weakness, dysarthria, and
      bilateral sensory impairment of the upper limbs, which worsened rapidly from the
      middle of March, although plasma glucose had been well controlled after the
      initiation of insulin therapy in the previous hospital. Contrast spinal MRI in
      our hospital revealed hyperintense lesions at the level of C4 to C5 and T10. The
      level of myelin basic protein was high (1,260 pg/ml) in the cerebrospinal fluid
      and serum anti-neurofascin antibody was negative. Nerve conduction study showed
      typical findings of demyelination at least 2 regions. Although anti-neurofascin
      antibody was negative, he was diagnosed with combined central and peripheral
      demyelination (CCPD) based on these clinical findings. After the repeated
      methylprednisolone pulse therapy for five times, the hyperintense lesions of the
      spinal cord disappeared gradually. He was bedridden at the beginning of his
      hospitalization but could ambulate with a cane on discharge 2 months after the
      admission. Then we received the result of anti-galactocerebroside antibody test
      as positive. This case suggested that high-dose steroid pulse therapy is safe and
      may be effective for anti-galactocerebroside antibody-positive CCPD.

PMID- 29187684
TI  - [A case of hereditary sensory and autonomic neuropathy type 1E with frontal lobe
      dysfunction as an initial symptom].
AB  - A 49-year-old man had developed gradually personality change, gait disturbance,
      and hearing loss for five years. On admission, he presented with frontal release
      signs, stuttering, vertical gaze palsy, sensorineural deafness, muscle rigidity,
      ataxia, and sensory disturbance with areflexia in the lower extremities. Brain
      MRI demonstrated atrophy in the cerebellum and midbrain tegmentum as well as
      cerebral atrophy, predominantly in the frontal lobe. He was tentatively diagnosed
      as progressive supranuclear palsy on the basis of clinical features and imagings.
      On nerve conduction study, no sensory nerve action potentials were elicited in
      the upper and lower extremities. Details of family history revealed a hereditary
      sensory neuropathy with autosomal dominant inheritance in his relatives. Because
      genetic analysis showed a rare missense mutation (c.1483T>C, p.Y495H) in DNA
      methyltransferase 1 gene, we diagnosed him as having hereditary sensory and
      autonomic neuropathy type 1E (HSAN1E). In addition, p.M232R mutation in prion
      protein gene was detected. It should be kept in mind that there are some patients
      with HSAN1E presenting with frontal lobe dysfunction as an initial symptom and
      with clinical features mimicking progressive supranuclear palsy.

PMID- 29187685
TI  - [A case of subarachnoid hemorrhage due to infective endocarditis by methicillin
      resistant coagulase-negative staphylococcus].
AB  - A 77-year-old man visited our hospital with unstable gait following 2 months of
      anorexia. Brain MRI showed multiple infarcts; cardiac echocardiography revealed
      mitral-valve vegetation; and blood culture revealed methicillin-resistant
      coagulase-negative staphylococci. The patient was diagnosed with infective
      endocarditis (IE). Subarachnoid hemorrhage (SAH) developed ten days after
      antibiotic treatment. Intracranial aneurysm was not found. We speculated that
      chronic inflammation of the cerebral arterial walls by bacteria of low virulence
      was associated with SAH complication. The vegetation disappeared following
      additional gentamicin administration and the patient recovered to walk.

PMID- 29187686
TI  - [Portal-systemic encephalopathy with bilateral thalamic and internal capsule
      lesions using diffusion-weighted MRI in a super-aged patient].
AB  - We describe the case of a 90-year-old woman who was hospitalized in July 2016 and
      subsequently experienced a sudden decline in consciousness level resulting in a
      state of deep coma. Involuntary movements were not observed, and bilateral
      Babinski signs were inconclusive. Diffusion-weighted MRI (DWI) of the brain
      showed bilateral hyperintensity in the thalamus and internal capsule, laboratory
      testing detected high levels of plasma ammonia, and an electroencephalogram
      showed delta waves and triphasic waves predominantly in the frontal lobe. Based
      on these results, treatment for hepatic encephalopathy was administered, which
      led to an improvement in consciousness level, a decrease in plasma ammonia
      levels, and a normalization in the DWI scan. Abdominal computed tomography scan
      showed no abnormality in the liver, but revealed an abnormal blood vessel leading
      from the ileocolic vein to the inferior vena cava; the patient was diagnosed with
      portal-systemic encephalopathy. In deep coma patients, acute encephalopathy with
      hyperammonemia is important for differential diagnosis when DWI shows high
      density legions in the thalamus and internal capsule.

PMID- 29187687
TI  - [Symmetrical lesions of the cerebral peduncles and internal capsules on MRI in a
      patient with extranodal NK/T cell lymphoma].
AB  - A 72-year-old man was admitted to our hospital because of subacute progressive
      consciousness disturbance. FLAIR images showed diffuse high intensity areas in
      the bilateral thalamus, basal ganglia, and white matter. Chest CT revealed a mass
      in the right lung. The patient was diagnosed with extranodal natural killer/T
      cell lymphoma (ENKL) according to the results of a biopsy of the right pulmonary
      mass. The FLAIR images showed diffuse white matter lesions, without a mass such
      as lymphomatosis cerebri. On diffusion-weighted images, symmetrical high
      intensity lesions of the cerebral peduncle and the internal capsule suggested
      high-density lymphoma cells around neurons. ENKL of the central nervous system
      and lung is a very rare neoplasm, and this case showed characteristic images.

PMID- 29187688
TI  - [Progressive dysarthria and bilateral sensory disturbance in a case of bilateral
      ventrolateral pontine infarction].
AB  - A rare case of bilateral ventrolateral pontine infarction in a 70-year-old man
      who developed progressive dysarthria and bilateral sensory disturbance is
      reported with literature review. He had been diagnosed with hypertension,
      dyslipidemia, and impaired glucose tolerance 10 years earlier. Ten days before
      admission, he was aware of the difficulty in walking and speaking, which
      gradually worsened. On admission he showed bilateral thermal hypoalgesia of face
      and lower extremities, dysarthria, dysphagia, and ataxic gait. High resolution
      three-dimensional MRI revealed bilateral ventrolateral pontine infarction with a
      large atherosclerotic plaque in the ventral side of the basilar artery, which led
      to a diagnosis of atherothrombotic brain infarction. The atherosclerotic plaque
      in the basilar artery was thought to be responsible for simultaneous occlusion of
      the bilateral short circumflex arteries of the pons.

PMID- 29187689
TI  - [A case of leptomeningeal melanomatosis with acute paraplegia and multiple
      cranial nerve palsies].
AB  - A 62-year-old man with acute paraplegia was transferred to our hospital. He had
      flaccid paraplegia and multiple cranial nerve palsies, such as mydriasis of the
      left pupil, abduction palsy of the left eye, hoarseness and dysphagia, but no
      meningeal irritation signs. MRI of the spinal canal showed swellings of the conus
      medullaris and the cauda equine, and also contrast enhancement of the spinal
      meninges. The cerebrospinal fluid (CSF) showed pleocytosis and protein increment.
      The lymph node was swollen in his right axilla. The biopsy specimen from the
      right axillary lymph node revealed metastasis of malignant melanoma
      histologically. Careful check-up of his whole body found a malignant melanoma in
      the subungual region of the right ring finger. Repeated cytological examination
      revealed melanoma cells in the CSF, confirming the diagnosis of leptomeningeal
      melanomatosis. His consciousness was gradually deteriorated. His family members
      chose supportive care instead of chemotherapy or surgical therapy after full
      information about his conditions. Finally, he died 60 days after transfer to our
      hospital. This is a rare case of leptomenigeal melanomatosis presenting with
      acute paraplegia and multiple cranial nerve palsies. Careful follow-up and
      repeated studies are vital for the early diagnosis of leptomenigeal melanomatosis
      in spite of atypical clinical presentation.

PMID- 29187690
TI  - [Treatment for paroxysmal sympathetic hyperactivity in amyotrophic lateral
      sclerosis patient].
AB  - We report a case of an 80-year-old man who contracted amyotrophic lateral
      sclerosis (ALS) 15 years ago, was put on a ventilator 8 years ago, and became
      locked in 3 years ago. Two years ago, he began to suffer from sudden symptoms of
      paroxysmal sympathetic hyperactivity (PSH) attacks (hot flushes, abnormal
      sweating, tachycardia, and increased blood pressure). One day, he developed
      multiple-organ failure. This failure healed in a few days, but PSH attacks
      remained. His catecholamine levels were abnormal: adrenaline, 215 pg/ml;
      noradrenaline, 5,960 pg/ml; and dopamine, 606 pg/ml. Diazepam was administered,
      which decreased both the number of PSH attacks and the catecholamine levels. When
      the dose was increased to 3 mg, the attacks stopped, whereas when the dose was
      reduced to 2 mg, the attacks relapsed. When the dose of 3 mg was continued, there
      was no relapse of the attacks and no re-rise in the catecholamine levels. These
      results show that diazepam alone has an effect on PSH attacks in ALS.

PMID- 29187691
TI  - [Tapia's syndrome following transesophageal echocardiography during an open-heart
      operation: a case report].
AB  - A 67-year-old man presented with hoarseness, dysarthria and deviation of the
      tongue to the left side the day after the open-heart operation under general
      anesthesia. Brain MRI demonstrated no causal lesion, and laryngoscope showed left
      vocal cord abductor palsy, so we diagnosed him with Tapia's syndrome (i.e.,
      concomitant paralysis of the left recurrent and hypoglossal nerve). His
      neurological symptoms recovered gradually and improved completely four months
      after the onset. Tapia's syndrome is a rare condition caused by the extra cranial
      lesion of the recurrent laryngeal branch of the vagus nerve and the hypoglossal
      nerve, and mostly described as a complication of tracheal intubation. In this
      case, transesophageal echo probe has been held in the left side of the pharynx,
      so compression to the posterior wall of pharynx by the probe resulted in this
      condition, and to the best of our knowledge, this is the first report of Tapia's
      syndrome due to transesophageal echocardiography during an open-heart operation.
      This rare syndrome should be considered as a differential diagnosis of dysarthria
      and tongue deviation after a procedure associated with compression to the
      pharynx.

PMID- 29187692
TI  - Nitrate Supply-Dependent Shifts in Communities of Root-Associated Bacteria in
      Arabidopsis.
AB  - Root-associated bacterial communities are necessary for healthy plant growth.
      Nitrate is a signal molecule as well as a major nitrogen source for plant growth.
      In this study, nitrate-dependent alterations in root-associated bacterial
      communities and the relationship between nitrate signaling and root-associated
      bacteria in Arabidopsis were examined. The bacterial community was analyzed by a
      ribosomal RNA intergenic spacer analysis (RISA) and 16S rRNA amplicon sequencing.
      The Arabidopsis root-associated bacterial community shifted depending on the
      nitrate amount and timing of nitrate application. The relative abundance of
      operational taxonomic units of 25.8% was significantly changed by the amount of
      nitrate supplied. Moreover, at the family level, the relative abundance of
      several major root-associated bacteria including Burkholderiaceae,
      Paenibacillaceae, Bradyrhizobiaceae, and Rhizobiaceae markedly fluctuated with
      the application of nitrate. These results suggest that the application of nitrate
      strongly affects root-associated bacterial ecosystems in Arabidopsis. Bulk soil
      bacterial communities were also affected by the application of nitrate; however,
      these changes were markedly different from those in root-associated bacteria.
      These results also suggest that nitrate-dependent alterations in root-associated
      bacterial communities are mainly affected by plant-derived factors in
      Arabidopsis. T-DNA insertion plant lines of the genes for two transcription
      factors involved in nitrate signaling in Arabidopsis roots, NLP7 and TCP20,
      showed similar nitrate-dependent shifts in root-associated bacterial communities
      from the wild-type, whereas minor differences were observed in root-associated
      bacteria. Thus, these results indicate that NLP7 and TCP20 are not major
      regulators of nitrate-dependent bacterial communities in Arabidopsis roots.

PMID- 29187693
TI  - A Simple and Efficient RNA Extraction Method from Deep-Sea Hydrothermal Vent
      Chimney Structures.
AB  - RNA-based microbiological analyses, e.g., transcriptome and reverse transcription
      quantitative PCR, require a relatively large amount of high quality RNA. RNA
      based analyses on microbial communities in deep-sea hydrothermal environments
      often encounter methodological difficulties with RNA extraction due to the
      presence of unique minerals in and the low biomass of samples. In the present
      study, we assessed RNA extraction methods for deep-sea vent chimneys that had
      complex mineral compositions. Mineral-RNA adsorption experiments were conducted
      using mock chimney minerals and Escherichia coli total RNA solution, and showed
      that detectable RNA significantly decreased possibly due to adsorption onto
      minerals. This decrease in RNA was prevented by the addition of sodium
      tripolyphosphate (STPP), deoxynucleotide triphosphates (dNTPs), salmon sperm DNA,
      and NaOH. The addition of STPP was also effective for RNA extraction from the
      mixture of E. coli cells and mock chimney minerals when TRIzol reagent and the
      RNeasy column were used, but not when the RNeasy PowerSoil total RNA kit was
      used. A combination of STPP, TRIzol reagent, the RNeasy column, and sonication
      resulted in the highest RNA yield from a natural chimney. This indirect
      extraction procedure is simple, rapid, inexpensive, and may be used for large
      scale RNA extraction.

PMID- 29187694
TI  - Efficacy and Safety of Pitavastatin in Children and Adolescents with Familial
      Hypercholesterolemia in Japan and Europe.
AB  - AIM: Children with Familial Hypercholesterolemia (FH) are widely prescribed
      statins, and it has been suggested that the effects of statins differ among
      ethnicities. We compared the efficacy and safety of pitavastatin in children and
      adolescents with FH in clinical trials conducted in Japan and Europe. METHODS:
      Low-density lipoprotein cholesterol (LDL-C) reductions, adjusted for confounding
      factors, and safety were compared between the studies in Japan and Europe. In the
      Japanese study, 14 males with heterozygous FH, aged 11.8+/-1.6 years, were
      randomized to 52-week double-blind treatment with 1 or 2 mg/day pitavastatin. In
      the European study, 106 children and adolescents with high risk hyperlipidemia
      (103 heterozygous FH), aged 10.6+/-2.9 years, were randomized to 12-week double
      blind treatment with 1, 2 or 4 mg/day pitavastatin or placebo; 84 of these
      patients and 29 new patients participated in a 52-week open-label extension
      study. RESULTS: Age, body weight and baseline LDL-C were identified as factors
      influencing LDL-C reduction. There were no significant differences in the
      adjusted mean percentage reduction in LDL-C in Japanese and European children by
      pitavastatin (24.5% and 23.6%, respectively at 1 mg/day and 33.5% and 30.8%,
      respectively at 2 mg/day). Pitavastatin was well tolerated without any difference
      in the frequency or nature of adverse events between the treatment groups, or
      between the studies. CONCLUSION: There were no significant differences between
      the efficacy or safety of pitavastatin in Japanese and European children and
      adolescents with FH, suggesting no relevant ethnic differences in the safety or
      efficacy of pitavastatin.

PMID- 29187695
TI  - MicroRNA-21-Regulated Activation of the Akt Pathway Participates in the
      Protective Effects of H2S against Liver Ischemia-Reperfusion Injury.
AB  - Maintaining a certain level of hydrogen sulfide (H2S) in ischemia-reperfusion
      (I/R) is essential for limiting injury to the liver. Exogenous H2S exerts
      protective effects against this injury, but the mechanisms remain unclear. Liver
      injury was induced in Wistar rats undergoing hepatic I/R for 30 min, followed by
      a 3-h reperfusion. Administration of GYY4137 (a slow-releasing H2S donor)
      significantly attenuated the severity of liver injury and was reflected by
      reduced inflammatory cytokine production and cell apoptosis, the levels of which
      were elevated by I/R, while DL-propargylglycine (PAG, an inhibitor of
      cystathionine gamma-lyase [CSE]) aggravated liver injury. Delivery of GYY4137
      significantly elevated the plasma levels of H2S and upregulated the expression of
      microRNA-21 (miR-21), leading to the activation of the Akt pathway, in rat livers
      subjected to I/R. To further investigate the protective mechanisms of H2S during
      liver I/R injury, we established a cell model of hypoxia/reoxygenation (H/R) by
      incubating Buffalo rat liver (BRL) cells under hypoxia for 4 h followed by
      normoxia for 10 h. The regulatory effect of miR-21 on the Akt pathway by
      downregulating phosphatase and tensin homolog (PTEN) was validated by luciferase
      assays. Incubation of sodium hydrosulfide (NaHS), an H2S donor, increased the
      expression of miR-21, attenuated the reduced cell viability and the increased
      apoptosis by H/R, in BRL cells. Anti-miR-21 abolished the protective effects of
      NaHS by inactivating the Akt pathway. In conclusion, the present results indicate
      the activation of the Akt pathway regulated by miR-21 participates in the
      protective effects of H2S against I/R-induced liver injury.

PMID- 29187696
TI  - Accuracy of follicle count and ovulation confirmation using magnetic resonance
      imaging in microminipigs with normal estrus cycles.
AB  - Magnetic resonance imaging (MRI) is suggested to be useful for counting follicles
      and confirming ovulation in microminipigs. However, its accuracy is unknown. We
      have compared the number of follicles counted by MRI to that of corpus
      hemorrhagicum confirmed directly by visual inspection. The follicles of 17
      microminipigs were counted by using ovarian MRI on a 0.4 Tesla MRI System every
      24 hr after estrus until follicle images disappeared. Then, we performed
      laparotomy to count their corpus hemorrhagicum. Significant correlation was
      observed between follicle counts obtained using MRI (5.18 +/- 1.78 per head) and
      the numbers of corpus hemorrhagicum (5.47 +/- 1.74 per head). In conclusion,
      follicle counts using 0.4-T MRI were reliable, and confirmed microminipig
      ovulation.

PMID- 29187697
TI  - Synthesis, characterization and in vitro release performance of the pegylated
      valnemulin prodrug.
AB  - Valnemulin, successfully developed by Sandoz in 1984, is a new generation
      derivative of pleuromutilin related to tiamulin. Valnemulin has low water
      solubility, a short half-life period, low bioavailability, and instability. The
      application of valnemulin was restricted. Therefore, finding a more moderate
      delivery system is necessary to improve the shortcomings of valnemulin. The
      purpose of the study was to improve the strong stability and the irritation
      caused by of valnemulin hydrochloride power through pegylated-valnemulin prodrug
      mode. The prepared pegylated-valnemulin prodrug was characterized and evaluated
      by in vitro release performance under buffer solutions with pH levels of 7.4 and
      3.6. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was
      determined by ultraviolet spectrophotometer and high performance liquid
      chromatography (HPLC). HPLC with evaporative light scattering detector was
      applied to determine the amount of PEG-succinic acid. The loading rate of
      valnemulin in PEG-succinic-valnemulin prodrug was 6.46%. PEG-succinic-valnemulin
      prodrug demonstrated a satisfactory solubility of valnemulin with 523 mg.ml-1 and
      excellent stability verified by the stability experiment. The result of the in
      vitro release test showed that the prepared PEG-valnemulin prodrug has controlled
      release ability and the release rate of valnemulin from PEG-valnemulin prodrug
      with a pH of 7.4 was 64.98%, which was higher than that of pH3.6 with release
      rate of 31.90%. Therefore, the prepared PEG-succinic-valnemulin prodrug has great
      application potential.

PMID- 29187698
TI  - Evaluation of Schistosoma japonicum thioredoxin peroxidase-1 as a potential
      circulating antigen target for the diagnosis of Asian schistosomiasis.
AB  - Asian schistosomiasis caused by Schistosoma japonicum is a serious zoonotic
      disease endemic in China, the Philippines and parts of Indonesia. Mass drug
      administration in endemic areas resulted to decline in disease severity and
      intensity. The low intensity of infection limits the use of current
      parasitological methods for schistosomiasis diagnosis. Detection of parasite
      circulating antigens might provide more informative result as it may indicate the
      true status of infection. In this study, S. japonicum thioredoxin peroxidase-1
      (SjTPx-1) a 22 kDa secreted antioxidant enzyme expressed throughout the life
      stages of the parasite was evaluated for its potential use as a biomarker for
      schistosomiasis japonica infection. Rabbit polyclonal antibody and mouse
      monoclonal antibodies (mAbs) were raised against the recombinant SjTPx-1 (rSjTPx
      1). The antibodies produced against the recombinant antigen was confirmed to
      detect the native SjTPx-1 in crude adult worm lysate. Likewise, the specific
      binding of mAbs to parasite TPx-1 and not to mammalian peroxiredoxin-1
      orthologues was also confirmed. The double antibody sandwich ELISA developed in
      this study was able to detect at least 1 ng/ml of rSjTPx-1. In addition, this
      method was able to detect the antigen from all serum samples of experimentally
      infected rabbit and mice. The diagnostic potential of SjTPx-1 in human clinical
      samples was also evaluated, in which 4 out of 10 stool-confirmed serum samples
      had detectable levels of the antigen. The results suggest that SjTPx-1 can be a
      potential biomarker for Asian zoonotic schistosomiasis.

PMID- 29187699
TI  - Establishment of an Alzheimer's disease model with latent herpesvirus infection
      using PS2 and Tg2576 double transgenic mice.
AB  - A relationship between Alzheimer's disease and herpes simplex virus infection has
      been pointed out. We established a model of Alzheimer's disease with a latent
      herpesvirus infection using a mouse model of Alzheimer's disease (PS2Tg2576) and
      examined the changes in amyloid beta (Abeta) in the brain. We crossbred female
      PS2 mice with male Tg2576 hemi mice and chose PS2Tg2576 mice. After priming 5
      week-old male mice with anti-pseudorabies virus swine serum, we challenged the
      mouse with 100 LD50 of YS-81, a wild-type strain of pseudorabies virus. The viral
      DNA was detected in nasal swabs by a reactivation test and in the trigeminal
      ganglia. At two months after infection, the Abeta40 and Abeta42 levels in the
      brains of the mice of the latently infected group were increased; the increase
      was greater than that observed in the noninfected group. Latent pseudorabies
      virus infection was established in PS2Tg2576 mice and the level of Abeta
      increased with the reactivation of the latent virus.

PMID- 29187701
TI  - Association between Concomitant Use of Acyclovir or Valacyclovir with NSAIDs and
      an Increased Risk of Acute Kidney Injury: Data Mining of FDA Adverse Event
      Reporting System.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are likely to be used concomitantly
      with acyclovir or valacyclovir in clinical practice, but the study on the safety
      of such combinations was seldom reported. The objective of the study was to
      investigate reports of acute kidney injury (AKI) events associated with the
      concomitant use of oral acyclovir or valacyclovir with an NSAID by using the
      United States Food and Drug Administration (FDA) Adverse Event Reporting System
      (AERS) database between January 2004 and June 2012. The frequency of AKI events
      in patients while simultaneously taking either acyclovir or valacyclovir and an
      NSAID was compared using the Chi-square test. The effect of concomitant use of
      acyclovir or valacyclovir and individual NSAIDs on AKI was analyzed by the
      reporting odds ratio (ROR). The results showed that AKI was reported as the
      adverse event in 8.6% of the 10923 patients taking valacyclovir compared with
      8.7% of the 2556 patients taking acyclovir (p=NS). However, AKI was significantly
      more frequently reported in patients simultaneously taking valacyclovir and an
      NSAID (19.4%) than in patients simultaneously taking acyclovir and an NSAID
      (10.5%) (p<0.01). The results also suggested that increased risk of AKI was
      likely associated with the concomitant use of valacyclovir and some NSAIDs such
      as loxoprofen, diclofenac, etodolac, ketorolac, piroxicam or lornoxicam. The case
      series from the AERS indicated that compared with acyclovir, valacyclovir is more
      likely to be affected by NSAIDs, and the concomitant use of valacyclovir with
      some NSAIDs might be associated with increased risk of AKI. The drug interactions
      with this specific combination of medications are worth exploring further.

PMID- 29187700
TI  - Sevoflurane preconditioning ameliorates lipopolysaccharide-induced cognitive
      impairment in mice.
AB  - Systemic inflammation induces brain neuronal inflammation, in turn causing acute
      cognitive disorders. Furthermore, neuronal inflammation is one cause of
      postoperative cognitive disorder (POCD) and delirium. However, no sufficiently
      established pharmacological treatment is available for neurocognitive
      inflammation. This study evaluated the possible neuroprotective effects of
      preconditioning with sevoflurane anesthesia on cognition and neuroinflammatory
      changes in an animal model of lipopolysaccharide (LPS)-induced systemic
      inflammation. Adult mice were randomly divided into (1) control, (2) 2%
      sevoflurane preconditioning for 1 h, (3) intraperitoneal 5 mg/kg LPS injection,
      and (4) 2% sevoflurane preconditioning for 1 h + LPS injection groups. At 24 h
      after 5 mg/kg LPS injection, microglial activation based on ionized calcium
      binding adapter molecule 1 (Iba-1) expression in the hippocampus was determined
      using immunostaining and immunoblotting. IL-1beta and IL-6 immunoblotting were
      used as inflammation markers, and beta-site of amyloid precursor protein cleaving
      enzyme 1 (BACE1) immunoblotting was performed to evaluate amyloid beta-protein
      (Abeta) accumulation. Long-term cognitive impairment was evaluated using fear
      conditioning tests. Intraperitoneal LPS increased levels of Iba-1 (150%),
      inflammation markers (160%), and Abeta accumulation (350%), and sevoflurane
      preconditioning suppressed these increases. Systemic LPS caused learning
      deficits. Sevoflurane also maintained long-term memory in mice receiving LPS
      injection. Sevoflurane preconditioning prevented long-term memory impairment in
      the mouse model administered systemic LPS by decreasing excessive microglial
      activation, inflammation, and Abeta accumulation. This study supports the
      hypothesis that sevoflurane preconditioning might also be beneficial for neuronal
      inflammation. Sevoflurane might be beneficial for reducing delirium and POCD.

PMID- 29187702
TI  - Individual nursing care for the elderly among China's aging population.
AB  - By the end of 2014, China had an elderly population age 60 or over totaling 212
      million; this group accounted for 15.5% of the country's total population of 1.37
      billion, which means that China has passed the threshold for an aging population.
      As China's population ages and the disease spectrum changes, nursing services for
      the elderly must be expanded. Given differences in the health status, financial
      situation, and family composition of each elderly person, modern society is
      tending towards individual nursing care for the elderly. Adapting to the changing
      composition of society by age will present new challenges.

PMID- 29187703
TI  - Paraganglioma as a risk factor for bone metastasis.
AB  - Malignant pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGL)
      are frequently associated with bone metastasis. Bone metastasis requires long
      term management and may lead to skeletal-related events (SREs) that remarkably
      reduce patients' quality of life (QOL). The aim of this study was to elucidate
      the risk factors for developing bone metastasis in patients with PPGL. The
      medical records of 40 consecutive adult patients with malignant PPGL at the
      National Hospital Organization Kyoto Medical Center between 2006 and 2016 were
      reviewed. SREs were defined as pathologic fracture, spinal cord compression, and
      the need for bone irradiation and/or surgery. PHEO (20/40) and PGL (20/40) were
      each present in 50% of the patients. Bone was the most frequent site of
      metastasis, detected in 60% (24/40). Bone metastasis was more frequent in
      patients with PGL (16/20, 80%) than in patients with PHEO (8/20, 40%) (p = 0.02).
      Half (12/24) of the patients with bone metastasis had at least one SRE. Extra
      skeletal invasion of the spine, defined as local infiltration to the surrounding
      tissue beyond the cortical bone, was more frequently observed in patients with
      bone metastasis associated with SREs than without them (p = 0.001). Careful
      follow-up and management are warranted especially in patients with PGL as a risk
      factor for bone metastasis and with extra-skeletal invasion of the spine as risk
      factor of SREs.

PMID- 29187704
TI  - Erratum to: Ultrasonic monitoring of the setting of silicone elastomeric
      impression materials.

PMID- 29187705
TI  - Overexpression of SMYD3 Is Predictive of Unfavorable Prognosis in Hepatocellular
      Carcinoma.
AB  - SET and MYND domain-containing protein 3 (SMYD3) is a kind of histone lysine
      methyltransferase, responsible for transcriptional activation as a member of an
      RNA polymerase complex. The ectopic expression of SMYD3 is proved to promote the
      progress of many kinds of cancers. In hepatocellular carcinoma (HCC), SMYD3 was
      demonstrated to promote the proliferation and metastasis of HCC cell lines, but
      the clinical significance of SMYD3 has not been elucidated. In the present study,
      we detected the expression of SMYD3 in 100 HCC tissues with immunohistochemistry
      and divided these tissue specimens into high-expression group and low-expression
      group according to the immunohistochemical score of SMYD3. Importantly, the
      intensity of SMYD3 immunoreactivity was significantly stronger in HCC tissues
      than that in adjacent normal tissues. Moreover, high expression levels of SMYD3
      were significantly associated with larger tumor size (P = 0.043), suggesting that
      SMYD3 could promote the proliferation of HCC. Moreover, patients with positive
      hepatitis B virus infection had higher expression levels of SMYD3 (P = 0.013).
      With univariate and multivariate analysis, we explored the prognostic
      significance of SMYD3 in HCC. As a result, high expression levels of SMYD3 were
      significantly correlated to the poorer clinical outcome of HCC patients (P =
      0.009) and were identified as an independent risk factor of HCC for predicting
      the unfavorable prognosis. In conclusion, overexpression of SMYD3 is an
      independent prognostic risk of unfavorable prognosis of HCC. We propose that the
      anti-SMYD3 therapy may be a potential approach to treat HCC.

PMID- 29187706
TI  - Capturing Early Changes in the Marine Bacterial Community as a Result of Crude
      Oil Pollution in a Mesocosm Experiment.
AB  - The results of marine bacterial community succession from a short-term study of
      seawater incubations at 4 degrees C to North Sea crude oil are presented herein.
      Oil was used alone (O) or in combination with a dispersant (OD). Marine bacterial
      communities resulting from these incubations were characterized by a
      fingerprinting analysis and pyrosequencing of the 16S rRNA gene with the aim of
      1) revealing differences in bacterial communities between the control, O
      treatment, and OD treatment and 2) identifying the operational taxonomic units
      (OTUs) of early responders in order to define the bacterial gene markers of oil
      pollution for in situ monitoring.After an incubation for 1 d, the distribution of
      the individual ribotypes of bacterial communities in control and oil-treated (O
      and OD) tanks differed. Differences related to the structures of bacterial
      communities were observed at later stages of the incubation. Among the early
      responders identified (Pseudoalteromonas, Sulfitobacter, Vibrio, Pseudomonas,
      Glaciecola, Neptunomonas, Methylophaga, and Pseudofulvibacter), genera that
      utilize a disintegrated biomass or hydrocarbons as well as biosurfactant
      producers were detected. None of these genera included obligate
      hydrocarbonoclastic bacteria (OHCB). After an incubation for 1 d, the abundances
      of Glaciecola and Pseudofulvibacter were approximately 30-fold higher in the OD
      and O tanks than in the control tank. OTUs assigned to the Glaciecola genus were
      represented more in the OD tank, while those of Pseudofulvibacter were
      represented more in the O tank. We also found that 2 to 3% of the structural
      community shift originated from the bacterial community in the oil itself, with
      Polaribacter being a dominant bacterium.

PMID- 29187707
TI  - Comparison of Prokaryotic and Eukaryotic Communities in Soil Samples with and
      without Tomato Bacterial Wilt Collected from Different Fields.
AB  - Biocontrol agents (BCA) effectively suppress soil-borne disease symptoms using
      natural antagonistic prokaryotes or eukaryotes. The main issue associated with
      the application of BCA is that disease reduction effects are unstable under
      different field conditions. In order to identify potentially effective BCA among
      several fields, we compared prokaryotic and eukaryotic communities in soil with
      and without tomato bacterial wilt from three different fields, each of which had
      the same field management and similar soil characteristics. Soil samples were
      collected from three fields and two depths because bacterial wilt pathogens were
      present in soil at a depth greater than 40 cm. We classified soil samples based
      on the presence or absence of the bacterial phcA gene, a key gene for bacterial
      wilt pathogenicity and tomato disease symptoms. Pyrosequencing of the prokaryotic
      16S rRNA gene and eukaryotic internal transcribed spacer region sequences showed
      that the diversity and richness of the communities mostly did not correlate with
      disease symptoms. Prokaryotic and eukaryotic community structures were affected
      more by regional differences than the appearance of disease. Several prokaryotes
      and eukaryotes were more abundant in soil that lacked disease symptoms, and eight
      prokaryotes and one eukaryote of this group were commonly detected among the
      three fields. Some of these taxa were not previously found in disease-suppressive
      soil. Our results suggest that several prokaryotes and eukaryotes control plant
      disease symptoms.

PMID- 29187708
TI  - Library Construction from Subnanogram DNA for Pelagic Sea Water and Deep-Sea
      Sediments.
AB  - Shotgun metagenomics is a low biased technology for assessing environmental
      microbial diversity and function. However, the requirement for a sufficient
      amount of DNA and the contamination of inhibitors in environmental DNA leads to
      difficulties in constructing a shotgun metagenomic library. We herein examined
      metagenomic library construction from subnanogram amounts of input environmental
      DNA from subarctic surface water and deep-sea sediments using two library
      construction kits: the KAPA Hyper Prep Kit and Nextera XT DNA Library Preparation
      Kit, with several modifications. The influence of chemical contaminants
      associated with these environmental DNA samples on library construction was also
      investigated. Overall, shotgun metagenomic libraries were constructed from 1 pg
      to 1 ng of input DNA using both kits without harsh library microbial
      contamination. However, the libraries constructed from 1 pg of input DNA
      exhibited larger biases in GC contents, k-mers, or small subunit (SSU) rRNA gene
      compositions than those constructed from 10 pg to 1 ng DNA. The lower limit of
      input DNA for low biased library construction in this study was 10 pg. Moreover,
      we revealed that technology-dependent biases (physical fragmentation and linker
      ligation vs. tagmentation) were larger than those due to the amount of input DNA.

PMID- 29187709
TI  - An efficient method for saliva collection from mature pigs to determine their
      enzymatic and electrolytic profiles.
AB  - In this study, a novel 'rope-assisted swab method' for the collection of saliva
      samples from 45 adult pigs was established and validated. This method was
      efficient for harvesting 2 milliliters or more of saliva from each of the pigs
      for subsequent analyses within two min. The amount of alpha-amylase and lipase in
      the collected saliva samples was between 38-6,655 and 2-52 U/l, respectively. For
      HCO3- and electrolytes, the range was between 9-40, 15-76, 4.3-48.5 and 7-65 mM
      for HCO3-, Na+, K+ and Cl-, respectively. No significant differences in the
      enzymatic and electrolytic profiles were observed among sows with a high average
      litter size (SHA), sows with a low average litter size (SLA) and non-pregnant
      gilts (NPG) in this study. Our work reveals the efficiency of this collection
      method for mature pigs, and enzymatic and electrolytic profiling of saliva, which
      may be a useful reference for multiple diagnostic applications.

PMID- 29187710
TI  - Hybrid origin of Asian aspermic Fasciola flukes is confirmed by analyzing two
      single-copy genes, pepck and pold.
AB  - Nuclear gene markers, phosphoenolpyruvate carboxykinase (pepck) and DNA
      polymerase delta (pold), have been developed for precise discrimination of
      Fasciola flukes instead of internal transcribed spacer 1. In this study, these
      two genes of 730 Fasciola flukes from eight Asian countries were analyzed. The
      results were compared with their mitochondrial NADH dehydrogenase subunit 1
      (nad1) lineages for obtaining a definitive evidence of the hybrid origin of
      aspermic Fasciola flukes. All the flukes categorized into the aspermic nad1
      lineages possessed both the fragment patterns of F. hepatica and F. gigantica
      (mixed types) in pepck and/or pold. These findings provide clear evidence for the
      hybrid origin of aspermic Fasciola lineages and suggest that "aspermic Fasciola
      flukes" should hereafter be called "hybrid Fasciola flukes".

PMID- 29187711
TI  - Prevalence, genotyping and risk factors of Giardia duodenalis from dogs in
      Vietnam.
AB  - This study was carried out to determine the prevalence, genotypes/assemblages and
      possible risk factors associated with Giardia duodenalis infection in dogs in
      central Vietnam. A total of 209 dog fecal samples, randomly collected from
      private owned dogs (n=105) and dogs from stores (n=104), were examined for
      Giardia cysts by microscopy. Positive samples were genotyped by PCR-sequence
      analysis of beta-giardin and triosephosphate isomerase genes markers. Risk
      factors were studied using a structured questionnaire and collected data were
      analyzed by univariate and multivariate logistic regression analyses. Results
      indicated that the overall infection rate was 8.6% (18/209) with the detected
      parasites were belonging to the non-zoonotic assemblages C and D. Age, gender and
      origin of animals were the main risk factors associated with G. duodenalis
      infection in dogs under study. Occurrence of infection was more likely in young
      animals compared to old ones and in females compared to males. Dogs originated
      from stores were more prone to Giardia infection compared to private owned
      counterparts.

PMID- 29187712
TI  - Seroepidemiology of non-primate hepacivirus (NPHV) in Japanese native horses.
AB  - Non-primate hepacivirus (NPHV) is recently identified as a closely related
      homologue of hepatitis C virus. The previous studies showed a high prevalence of
      NPHV infection among Japanese domestic horses originated from abroad. The
      historical distribution of NPHV among horses in Japan, therefore, is still
      unknown. In this study, seroepidemiological study of NPHV was conducted using 335
      sera from five breeds of Japanese native horses. These horses are maintained as
      the pedigree and are reared apart from other horse breeds. The detection of
      antibodies against NPHV were conducted by western blot analysis using the
      recombinant protein of the NPHV core protein. The antibodies against NPHV were
      detected in all five breeds, 83 out of 335 (23.4%) horses. These results
      suggested that NPHV was circulating among Japanese native horses.

PMID- 29187714
TI  - [Preparation and Biological Characterization of Limulus Factor G-activating
      Substance of Aspergillus spp.]
AB  - Aspergillus is a medically important fungal genus that causes a life-threatening
      infection known as aspergillosis in immunocompromised patients. beta-1,3-Glucan
      is detected in the plasma of patients with aspergillosis and appears to be useful
      for the diagnosis of aspergillosis. In this study, we cultured Aspergillus spp.
      in a chemically defined liquid medium and prepared an Aspergillus water-soluble
      fraction (ASWS) from the culture supernatants. ASWS was found to be primarily
      composed of polysaccharides and proteins. Nuclear magnetic resonance analysis
      suggested that ASWS is a complex carbohydrate, consisting of alpha-1,3-glucan,
      beta-1,3-glucan, galactomannan, and protein. The ASWS from Aspergillus fumigatus
      showed limulus factor G activity, whereas zymolyase-treated ASWS did not. ASWS
      was eliminated from the blood more rapidly than Aspergillus solubilized cell wall
      beta-glucan. We analyzed the reactivity of human immunoglobulin towards ASWS by
      an enzyme-linked immunosorbent assay. Anti-ASWS antibodies were detected in human
      sera, with titers differing among individuals. This study demonstrated that the
      ASWS corresponds to the limulus factor G-activating substance found in the blood
      of patients with aspergillosis.

PMID- 29187713
TI  - Injury and mechanism of recombinant E. coli expressing STa on piglets colon.
AB  - Enterotoxigenic Escherichia coli (ETEC) is primary pathogenic bacteria of piglet
      diarrhea, over two thirds of piglets diarrhea caused by ETEC are resulted from
      STa-producing ETEC strains. This experiment was conducted to construct the
      recombinant E. coli expressing STa and study the injury and mechanism of
      recombinant E. coli expressing STa on 7 days old piglets colon. Twenty-four 7
      days old piglets were allotted to four treatments: control group, STa group (2 *
      109 CFU E. coli LMG194-STa), LMG194 group (2 * 109 CFU E. coli LMG194) and K88
      group (2 * 109 CFU E. coli K88). The result showed that E. coli infection
      significantly increased diarrhea rates; changed DAO activity in plasma and colon;
      damaged colonic mucosal morphology including crypt depth, number of globet cells,
      density of lymphocytes and lamina propria cell density; substantially reduced
      antioxidant capacity by altering activities of GSH-Px, SOD, and TNOS and
      productions of MDA and H2O2; obviously decreased AQP3, AQP4 and KCNJ13 protein
      expression levels; substantially altered the gene expression levels of
      inflammatory cytokines. Conclusively, STa group had the biggest effect on these
      indices in four treatment groups. These results suggested that the recombinant
      strain expressed STa can induce piglets diarrhea and colonic morphological and
      funtional damage by altering expression of proteins connect to transportation
      function and genes associated with intestinal injury and inflammatory cytokines.

PMID- 29187715
TI  - [A Silkworm Infection Model to Evaluate Antifungal Drugs for Cryptococcosis].
AB  - The development of effective drugs against fungal diseases involves performing
      infection experiments in animals to evaluate candidate therapeutic compounds.
      Cryptococcus neoformans is a pathogenic fungus that causes deep mycosis,
      resulting in respiratory illness and meningitis. Here we describe a silkworm
      system established to evaluate the safety and efficacy of therapeutic drugs
      against infection by Cryptococcus neoformans and the advantages of this system
      over other animal models. The silkworm assay system has two major advantages: 1)
      silkworms are less expensive to rear and their use is less problematic than that
      of mammals in terms of animal welfare, and 2) in vivo screenings for identifying
      candidate drugs can be easily performed using a large number of silkworms. The
      pharmacokinetics of compounds are consistent between silkworms and mammals.
      Moreover, the ED50 values of antibiotics are concordant between mammalian and
      silkworm infection models. Furthermore, the body size of silkworms makes them
      easy to handle in experimental procedures compared with other invertebrate
      infectious experimental systems, and accurate amounts of pathogens and chemicals
      can be injected fairly easily. These advantages of silkworms as a host animal
      make them useful for screening candidate drugs for cryptococcosis.

PMID- 29187716
TI  - [Possible Involvement of Surface Antigen Protein 2 in the Morphological
      Transition and Biofilm Formation of Candida albicans].
AB  - Surface antigen protein 2 (Csa2) is a member of the Candida albicans Common in
      Fungal Extracellular Membranes (CFEM) protein superfamily. We previously
      established its role in iron acquisition in C. albicans. However, the other roles
      of Csa2 remain unknown. Here, we compared growth, morphological transition, and
      biofilm formation among wild-type, Csa2-mutant, and complemented strains of C.
      albicans. Deletion of the Csa2 gene resulted in smaller and reduced colony
      growth, significant attenuation of the dimorphic transition under serum-inducing
      conditions, and reduced biofilm formation; complementation restored these levels
      to those of the wild-type. Our findings demonstrated that Csa2 participated in
      yeast-to-hyphae morphological switching under serum-inducing conditions and
      contributed to the biofilm formation of C. albicans. This work, therefore,
      provides novel insights into the potential roles of Csa2 in virulence of C.
      albicans.

PMID- 29187717
TI  - [A Case of Liver Dysfunction Requiring Hospital Admission after Taking Oral
      Itraconazole for the Treatment of Kerion Celsi].
AB  - 67-year-old female patient developed drug-induced liver dysfunction after
      taking oral itraconazole (ITCZ) for the treatment of kerion celsi. Red papules
      appeared on the temporal area of the patient one month prior to her visit to our
      clinic. The patient presented with a nodule with yellow crust, erosion,
      infiltration, and hair loss on the area. Diagnosis of kerion celsi caused by
      Trichophyton rubrum was made from clinical, pathological, and mycological
      findings. Laboratory data showed normal liver function, and the patient was not
      taking any other medication, thus, daily oral ITCZ 100 mg was started. The skin
      lesion improved, but severe liver dysfunction was found 1 month after starting
      ITCZ. Oral ITCZ was therefore terminated, and the patient was admitted to a
      medical ward for the treatment of liver dysfunction. Hepatobiliary enzymes
      increased after admission: AST 232 IU/L, ALT 465 IU/L, T-bil 6.1 mg/dL, and D-bil
      3.9 mg/dL. The patient was kept at rest and was given oral ursodeoxycholic acid.
      Hepatobiliary enzymes returned to normal level 2 1/2 months after starting ITCZ.
      The skin lesion healed without further treatment. No recurrence was observed. It
      is noteworthy that liver function has to be carefully monitored during treatment
      with oral ITCZ.

PMID- 29187718
TI  - [Affinity of Luliconazole for Human Nail Derived Keratin].
AB  - Affinity of Luliconazole (LLCZ), an antifungal drug used for topical treatment
      of onychomycosis in Japan, to nail keratin was demonstrated. Efinaconazole (EFCZ)
      was used as a reference drug. Drugs at fixed concentrations were added to 4 ml of
      buffer solution containing 40 mg of nail keratin powder prepared from healthy
      volunteers or from tinea unguium patients. The mixtures were shaken at 37C, and
      adsorption and desorption rates of the drug in nail keratin were measured.
      Theoretical analysis using the Freundlich adsorption isotherm was applied to
      eliminate effects of testing conditions on the results. Results showed that
      compared with EFCZ, LLCZ exhibited high adsorption rates and low desorption rates
      in nail keratins. These results were verified by Freundlich analysis, in which
      adsorption coefficient (KadsF) and desorption coefficient (KadsF) of LLCZ were 5
      7 times and about 2 times higher than EFCZ, respectively. In addition, antifungal
      activity against Trichophyton rubrum of the desorbed LLCZ samples was determined
      using disk diffusion assay. In conclusion, LLCZ is considered to possess high
      affinity to nail keratin. LLCZ, therefore, can be retained in the nail as a
      reservoir and continuously desorbed at the infection site to exhibit antifungal
      activity against pathogenic fungi. The pharmacokinetics of LLCZ in the nail is
      believed to differ from that of EFCZ. As adsorption and desorption rates of the
      two drugs in nail keratin tended to be different between healthy volunteers and
      patients, further detailed study is needed.

PMID- 29187719
TI  - [Small Animal Aspergillosis and Cryptococcosis in Japan].
AB  - Canine and feline upper respiratory tract (URT) infection due to Aspergillus
      spp. is considered an emerging disease, with the number of reported cases
      continuing to rise in Japan. Aspergillus fumigatus has been the most frequently
      reported etiologic agent of sino-orbital aspergillosis in dogs and cats; the
      other Aspergillus species, Aspergillus felis, Aspergillus fischeri, Aspergillus
      udagawae, Aspergillus viridinutans, and A. fumigatus, have also been implicated
      in feline cases. The minimum inhibitory concentrations (MICs) of antifungal drugs
      are elevated for these cryptic species compared with A. fumigatus. Some reports
      showed that the feline infections due to cryptic species did not respond to
      treatment with antifungal drugs. These results suggest that species
      identification and antifungal susceptibility testing of infecting agents are
      important to ensure effective treatment of feline URT aspergillosis. Feline
      cryptococcosis in Japan is typically attributed to Cryptococcus neoformans var.
      grubii. We isolated a fluconazole-resistant strain of C. grubii from a feline
      cryptococcosis. The predicted amino acid sequence of the lanosterol 14-alpha
      demethylase gene (ERG11) protein in the isolate was identical to that of the C.
      grubii reference strain. RT-PCR analysis of ERG11 and ATP binding cassette (ABC)
      transporter-encoding gene (AFR1) indicated that the isolate had increased
      transcription factor function for ERG11 and AFR1 compared with fluconazole
      susceptible strains. This observation, in combination with the lack of resistance
      to other azoles (that is, lack of cross resistance), suggests that resistance in
      our isolate was the result of overexpression of the endogenous ERG11 and ABC
      transporter. Further ecological and epidemiological studies on small animal
      mycoses in Japan are needed to monitor the emergence of antifungal drug resistant
      strains.

PMID- 29187720
TI  - [Histopathological Diagnosis of Fungal Sinusitis and Variety of its Etiologic
      Fungus].
AB  - Fungal sinusitis is divided into two categories depending on mucosal invasion by
      fungus, i.e., invasive and noninvasive. Invasive fungal sinusitis is further
      divided into acute and chronic disease based on time course. Noninvasive fungal
      sinusitis includes chronic noninvasive sinusitis (fungal ball type) and allergic
      fungal sinusitis. Chronic noninvasive sinusitis is the most predominant fungal
      sinusitis in Japan, followed by allergic fungal sinusitis. Invasive fungal
      sinusitis is rare. Hyphal tissue invasion is seen in invasive fungal sinusitis.
      Acute invasive fungal sinusitis demonstrates hyphal vascular invasion while
      chronic invasive fungal sinusitis usually does not. Fungal tissue invasion is
      never found in noninvasive sinusitis. A fungal ball may exist adjacent to sinus
      mucosa, but its hyphae never invade the mucosa. Fungal balls sometimes contain
      conidial heads and calcium oxalate, which aid in identifying the fungus in the
      tissue. Allergic fungal sinusitis is characterized by allergic mucin that is
      admixed with numerous eosinophils and sparsely scattered fungal elements.
      Histopathology is important in classifying fungal sinusitis, especially in
      confirming tissue invasion by the fungus.

PMID- 29187721
TI  - [Survival Strategies of Aspergillus in the Human Body].
AB  - The human body is a hostile environment for Aspergillus species, which
      originally live outside the human body. There are lots of elimination mechanisms
      against Aspergillus inhaled into the human body, such as high body temperature,
      soluble lung components, mucociliary clearance mechanism, or responses of
      phagocytes. Aspergillus fumigatus, which is the primary causative agent of human
      infections among the human pathogenic species of Aspergillus, defend itself from
      the hostile human body environment by various mechanisms, such as
      thermotolerance, mycotoxin production, and characteristic morphological features.
      Here we review mechanisms of defense in Aspergillus against elimination from the
      human body.

PMID- 29187723
TI  - [Term 16].

PMID- 29187722
TI  - [The Plasma (1->3)-beta-D-glucan Assay, a Japanese Contribution to the Diagnosis
      of Invasive Fungal Infection].
AB  - In 1985, a (1->3)-beta-D-glucan assay based on the discovery of a (1->3)-beta-D
      glucan-sensitive coagulation factor in the horseshoe crab amebocytes was
      developed in Japan, as a test aid in the diagnosis of invasive fungal infections.
      After many clinical trials, it has now been incorporated in practice guidelines
      both in Japan and abroad for the diagnosis and management of invasive fungal
      infection, and is now available worldwide. In Japan, however, two commercial kits
      that differ widely in sensitivity to (1->3)-beta-D-glucan are used; namely, the
      colorimetric and the turbidimetric assays. Thus, attention must be paid when
      comparing measurement values between the two tests. In most cases, one pg/ml of
      the latter corresponds to about 7 pg/ml of the former. This raises the cutoff
      value of the turbidimetric assay far higher than that of the colorimetric assay,
      raising concern about missing many true cases of invasive fungal infections. The
      detection limit of the turbidimetric method is equivalent to as high as 60 pg/ml
      if converted to the colorimetric measurement. Thus, early diagnosis will be
      difficult to make based on detection of a rise in the beta-D-glucan level in the
      lower range of concentration. The kits used overseas also differ in sensitivity;
      thus, global standardization or harmonization will be required to establish inter
      assay data comparability and to enhance the usefulness of the tests. In the
      future, genetic engineering may provide an alternative source of the coagulation
      pathway enzymes other than the horseshoe crabs, in accordance with the global
      trends in animal protection, and bring about new opportunities for
      standardization.

PMID- 29187724
TI  - In-Depth Insight Into the Mechanisms of Cardiac Dysfunction in Patients With
      Childhood Cancer After Anthracycline Treatment Using Layer-Specific Strain
      Analysis.
AB  - BACKGROUND: Anthracycline cardiotoxicity affects clinical outcomes, and its early
      detection using methods that rely on conventional echocardiography, such as left
      ventricular ejection fraction (LVEF) is difficult. This study aimed to evaluate
      the characteristics and the differences in cardiac dysfunction among childhood
      cancer survivors in 3 age groups using layer-specific strain analysis in a wide
      age range.Methods and Results:The 56 patients (median age: 15 [range: 6.8-40.2]
      years) who had been treated with anthracycline for childhood cancer were divided
      into 3 age groups (C1: 6-12 years, C2: 13-19 years, C3: 20-40 years) after
      anthracycline treatment, and 72 controls of similar ages were divided into 3
      corresponding groups (N1, N2, and N3). Layer-specific longitudinal strain (LS)
      and circumferential strain (CS) of 3 myocardial layers (endocardium,
      midmyocardium, and epicardium) were determined using echocardiography. Myocardial
      damage had not occurred yet in C1. Endocardial CS at the basal level was less in
      C2 than in N2. Endocardial CS at all levels and midmyocardial CS at the basal and
      papillary levels were lower in C3 than in N3. LVEF and LS were not significantly
      different between patients and controls. CONCLUSIONS: Among survivors of
      childhood cancer, impaired myocardial deformation starts in adolescence and
      extends from the endocardium towards the epicardium and from the base towards the
      apex with age. These findings are a novel insight into the time course of
      anthracycline cardiotoxicity.

PMID- 29187725
TI  - Mobbing (bullying at work) in Italy: characteristics of successful court cases.
AB  - BACKGROUND: Mobbing (bullying at work) refers to a form of psychological
      harassment that occurs in the workplace, in which the victim must be
      systematically and continuously persecuted for a long period of time. The aim of
      this work is to analyze the court judgments related to mobbing. METHODS: The
      data, collected from a website that included judgments from an Italian court,
      were analyzed according to the literature, identifying the type of victims,
      consequences, methods of harassment, type of mobbers, and compensation decided by
      the court. RESULTS: A total of 35 court sentences were analyzed. The findings
      showed that the duration of the mobbing campaign was on average 1.5 years and
      that the frequency of harassment was every day in most cases. In the majority of
      cases (17, 48.6%) the mobbing occurred in a private company. The gender of the
      victims who reported the mobbing experience was predominantly female (19, 54.3%),
      and on average, the victims were 44.54 years of age. The victims were classified
      as captives (12, 34.3%), scapegoats (8, 22.9%), ambitious (8, 22.9%), passives
      (5, 14.3%) and hypochondriacs (2, 5.7%). The mobbers were predominantly men (25,
      71.4%) and on average 53.20 years of age. They were classified as casual (12,
      34.3%), sadists (11, 31.4%), instigators (8, 22.9%) and choleric (4, 11.4%). The
      witnesses were described in the majority of cases as active, while the asymmetry
      of power was vertical. On average, the victims suffered 4.9 types of harassment,
      and the most cited consequences were anxiety disorder and physical symptoms. The
      motives for beginning the mobbing campaign were principally related to
      difficulties in relationships. The compensation imposed by the court ranged from
      less than 20,000 to more than 70,000 euros. CONCLUSIONS: The sentences analyzed
      showed that for different types of victims, there are behaviors, motives and
      consequences that are linked to different types of perpetrators.

PMID- 29187726
TI  - Increased levels of interleukin 27 in patients with early clinical stages of non
      small cell lung cancer.
AB  - INTRODUCTION    Interleukin 27 (IL-27) is a cytokine secreted mostly by antigen
      presenting cells. It is important for the immune polarization of T helper-1 (Th1)
      cells, and its role in interstitial lung diseases (ILDs) and lung cancer has been
      investigated. OBJECTIVES    We assessed IL-27 expression in the lower airways of
      patients with selected ILDs and early-stage non-small cell lung cancer (NSCLC).
      PATIENTS AND METHODS    IL-27 concentrations were examined by an enzyme-linked
      immunosorbent assay in bronchoalveolar lavage (BAL) fluid supernatants collected
      from patients with pulmonary sarcoidosis (PS; n = 30), extrinsic allergic
      alveolitis (EAA; n = 14), idiopathic pulmonary fibrosis (IPF; n = 12),
      nonspecific interstitial pneumonia (NSIP; n = 14), and NSCLC stages I to IIa (n =
      16) with peripheral localization, and in controls (n = 14). The major lymphocyte
      subsets in BAL fluid were phenotyped, and intracellular IL-27 expression was
      evaluated by flow cytometry.  RESULTS    IL-27 concentrations in BAL fluid
      supernatants were significantly increased in Th1-mediated conditions such as EAA
      and PS, but not in IPF or NSIP. The highest IL-27 levels (median [SEM], 16.9
      [17.5] pg/ml) were reported for NCSLC, and the lowest-for controls (median [SEM],
      0.4 [0.2] pg/ml). IL-27 was undetectable in corticosteroid-treated patients with
      PS. Both CD4+ and CD8+ lymphocytes were positive for IL-27; they were a possible
      local source of IL-27 because the cytokine levels were positivelysignificantly
      correlated with the total number of lymphocytes, including CD4+ cells.
      CONCLUSIONS    Our results support the Th1-linked activity of IL-27in ILDs. Early
      stageNSCLC is characterizedby high IL-27expression in the lower airways. IL-27 is
      produced by a high percentage of CD4+ and CD8+ cells in BAL fluid, both in
      patients and controls.

PMID- 29187727
TI  - MicroRNA-588 is downregulated and may have prognostic and functional roles in
      human breast cancer.
AB  - BACKGROUND We explored the expression pattern, prognostic potential, and
      functional role of microRNA-588 (miR-588) in human breast cancer (BC). MATERIAL
      AND METHODS The expression pattern of miR-588 was assessed by qPCR in BC cell
      lines and human BC carcinomas. The correlations between miR-588 and BC patients'
      clinicopathological characteristics, as well as BC patients' overall survival,
      were statistically assessed. In in vitro culture, MCF-7 and MDA-MB-231 cells were
      infected with lentivirus to overexpress endogenous miR-588. The subsequent
      effects of miR-588 upregulation on BC cell proliferation and cisplatin
      chemosensitivity were examined. RESULTS miR-588 was found to be significantly
      downregulated in both BC cell lines and carcinoma tissues of BC patients. Low
      expression of miR-588 was closely correlated with BC patients' poor prognosis of
      TNM stage, lymph node metastasis, and estrogen receptor status. In addition,
      patients with low miR-588-expressing carcinomas had much shorter overall
      survival. In MCF-7 and MDA-MB-231 cells, lentiviral infection induced significant
      miR-588 upregulation, and miR-588 upregulation had an anti-tumor effect in BC
      cells by significantly inhibiting cancer proliferation and increasing cisplatin
      chemosensitivity. CONCLUSIONS miR-588 is downregulated in BC and its aberrant
      expression is closely associated with patients' poor prognosis and overall
      survival, thus suggesting a biomarker role. miR-588 also has anti-tumor function
      in BC, making it a potential therapeutic target for BC treatment.

PMID- 29187728
TI  - Pleomorphic Adenoma of the Posterior Surface of the Soft Palate Causing Sleep
      Disturbance: A Case Report.
AB  - BACKGROUND Pleomorphic adenoma is the most common benign tumor arising in the
      salivary gland. The signs and symptoms of pleomorphic adenoma of the minor
      salivary glands vary, depending on the anatomical site involved. A rare case of
      pleomorphic adenoma of the posterior surface of the soft palate is reported that
      caused sleep disturbance, which was resolved with endoscopic surgical treatment.
      CASE REPORT A 32-year-old woman experienced snoring and mouth-breathing during
      sleep. Flexible fiberoptic nasopharyngoscopy imaging of the oropharyngeal passage
      showed obstruction by a tumor the soft palate, which obstructed the oropharyngeal
      passage. The tumor was excised using endoscopic-assisted transoral surgery and
      measure 3*2 cm in diameter. Histopathology showed a benign pleomorphic adenoma of
      the minor salivary gland. Following surgical excision of the tumor, the patient's
      sleep improved. CONCLUSIONS To our knowledge, this is the first case of a
      pleomorphic adenoma of the posterior surface of the soft palate, causing sleep
      disturbance, removed by endoscopic-assisted transoral surgery following pre
      operative flexible fiberoptic nasopharyngoscopy imaging of the oropharyngeal
      passage.

PMID- 29187729
TI  - Inference of differentiation time for single cell transcriptomes using cell
      population reference data.
AB  - Single-cell RNA sequencing (scRNA-seq) is a powerful method for dissecting
      intercellular heterogeneity during development. Conventional trajectory analysis
      provides only a pseudotime of development, and often discards cell-cycle events
      as confounding factors. Here using matched cell population RNA-seq (cpRNA-seq) as
      a reference, we developed an "iCpSc" package for integrative analysis of cpRNA
      seq and scRNA-seq data. By generating a computational model for reference
      "biological differentiation time" using cell population data and applying it to
      single-cell data, we unbiasedly associated cell-cycle checkpoints to the internal
      molecular timer of single cells. Through inferring a network flow from cpRNA-seq
      to scRNA-seq data, we predicted a role of M phase in controlling the speed of
      neural differentiation of mouse embryonic stem cells, and validated it through
      gene knockout (KO) experiments. By linking temporally matched cpRNA-seq and scRNA
      seq data, our approach provides an effective and unbiased approach for
      identifying developmental trajectory and timing-related regulatory events.

PMID- 29187730
TI  - Genome-wide analysis in UK Biobank identifies four loci associated with mood
      instability and genetic correlation with major depressive disorder, anxiety
      disorder and schizophrenia.
AB  - Mood instability is a core clinical feature of affective and psychotic disorders.
      In keeping with the Research Domain Criteria approach, it may be a useful
      construct for identifying biology that cuts across psychiatric categories. We
      aimed to investigate the biological validity of a simple measure of mood
      instability and evaluate its genetic relationship with several psychiatric
      disorders, including major depressive disorder (MDD), bipolar disorder (BD),
      schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder
      and post-traumatic stress disorder (PTSD). We conducted a genome-wide association
      study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK
      Biobank, identifying four independently associated loci (on chromosomes 8, 9, 14
      and 18), and a common single-nucleotide polymorphism (SNP)-based heritability
      estimate of ~8%. We found a strong genetic correlation between mood instability
      and MDD (r g = 0.60, SE = 0.07, p = 8.95 * 10-17) and a small but significant
      genetic correlation with both schizophrenia (r g = 0.11, SE = 0.04, p = 0.01) and
      anxiety disorders (r g = 0.28, SE = 0.14, p = 0.04), although no genetic
      correlation with BD, ADHD or PTSD was observed. Several genes at the associated
      loci may have a role in mood instability, including the DCC netrin 1 receptor
      (DCC) gene, eukaryotic translation initiation factor 2B subunit beta (eIF2B2),
      placental growth factor (PGF) and protein tyrosine phosphatase, receptor type D
      (PTPRD). Strengths of this study include the very large sample size, but our
      measure of mood instability may be limited by the use of a single question.
      Overall, this work suggests a polygenic basis for mood instability. This simple
      measure can be obtained in very large samples; our findings suggest that doing so
      may offer the opportunity to illuminate the fundamental biology of mood
      regulation.

PMID- 29187732
TI  - Structural basis of respiratory syncytial virus subtype-dependent neutralization
      by an antibody targeting the fusion glycoprotein.
AB  - A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and
      passive prophylaxis with the antibody palivizumab is restricted to high-risk
      infants. Recently isolated antibodies 5C4 and D25 are substantially more potent
      than palivizumab, and a derivative of D25 is in clinical trials. Here we show
      that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal
      structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall
      binding mode of 5C4 is similar to that of D25, but their angles of approach are
      substantially different. Mutagenesis and virological studies demonstrate that RSV
      F residue 201 is largely responsible for the subtype specificity of 5C4. These
      results improve our understanding of subtype-specific immunity and the
      neutralization breadth requirements of next-generation antibodies, and thereby
      contribute to the design of broadly protective RSV vaccines.

PMID- 29187733
TI  - Controlling thermal reactivity with different colors of light.
AB  - The ability to switch between thermally and photochemically activated reaction
      channels with an external stimulus constitutes a key frontier within the realm of
      chemical reaction control. Here, we demonstrate that the reactivity of
      triazolinediones, powerful coupling agents in biomedical and polymer research,
      can be effectively modulated by an external photonic field. Specifically, we show
      that their visible light-induced photopolymerization leads to a quantitative
      photodeactivation, thereby providing a well-defined off-switch of their thermal
      reactivity. Based on this photodeactivation, we pioneer a reaction manifold using
      light as a gate to switch between a UV-induced Diels-Alder reaction with
      photocaged dienes and a thermal addition reaction with alkenes. Critically, the
      modulation of the reactivity by light is reversible and the individually
      addressable reaction pathways can be repeatedly accessed. Our approach thus
      enables a step change in photochemically controlled reactivity, not only in small
      molecule ligations, yet importantly in controlled surface and photoresist design.

PMID- 29187731
TI  - Contributions of Zea mays subspecies mexicana haplotypes to modern maize.
AB  - Maize was domesticated from lowland teosinte (Zea mays ssp. parviglumis), but the
      contribution of highland teosinte (Zea mays ssp. mexicana, hereafter mexicana) to
      modern maize is not clear. Here, two genomes for Mo17 (a modern maize inbred) and
      mexicana are assembled using a meta-assembly strategy after sequencing of 10
      lines derived from a maize-teosinte cross. Comparative analyses reveal a high
      level of diversity between Mo17, B73, and mexicana, including three Mb-size
      structural rearrangements. The maize spontaneous mutation rate is estimated to be
      2.17 * 10-8 ~3.87 * 10-8 per site per generation with a nonrandom distribution
      across the genome. A higher deleterious mutation rate is observed in the
      pericentromeric regions, and might be caused by differences in recombination
      frequency. Over 10% of the maize genome shows evidence of introgression from the
      mexicana genome, suggesting that mexicana contributed to maize adaptation and
      improvement. Our data offer a rich resource for constructing the pan-genome of
      Zea mays and genetic improvement of modern maize varieties.

PMID- 29187734
TI  - O-GlcNAcylation is required for B cell homeostasis and antibody responses.
AB  - O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc
      modification. O-GlcNAcylation is increased after cross-linking of the B-cell
      receptor (BCR), but the physiological function of this reaction is unknown. Here
      we show that lack of Ogt in B-cell development not only causes severe defects in
      the activation of BCR signaling, but also perturbs B-cell homeostasis by
      enhancing apoptosis of mature B cells, partly as a result of impaired response to
      B-cell activating factor. O-GlcNAcylation of Lyn at serine 19 is crucial for
      efficient Lyn activation and Syk interaction in BCR-mediated B-cell activation
      and expansion. Ogt deficiency in germinal center (GC) B cells also results in
      enhanced apoptosis of GC B cells and memory B cells in an immune response,
      consequently causing a reduction of antibody levels. Together, these results
      demonstrate that B cells rely on O-GlcNAcylation to maintain homeostasis,
      transduce BCR-mediated activation signals and activate humoral immunity.

PMID- 29187736
TI  - Rules for processing genetic data for research purposes in view of the new EU
      General Data Protection Regulation.
AB  - Genetic data contain sensitive health and non-health-related information about
      the individuals and their family members. Therefore, adopting adequate privacy
      safeguards is paramount when processing genetic data for research or clinical
      purposes. One of the major legal instruments for personal data protection in the
      EU is the new General Data Protection Regulation (GDPR), which has entered into
      force in May 2016 and repealed the Directive 95/46/EC, with an ultimate goal of
      enhancing effectiveness and harmonization of personal data protection in the EU.
      This paper explores the major provisions of the new Regulation with regard to
      processing genetic data, and assesses the influence of such provisions on
      reinforcing the legal safeguards when sharing genetic data for research purposes.
      The new Regulation attempts to elucidate the scope of personal data, by
      recognizing pseudonymized data as personal (identifiable) data, and including
      genetic data in the catalog of special categories of data (sensitive data).
      Moreover, a set of new rules is laid out in the Regulation for processing
      personal data under the scientific research exemption. For instance, further use
      of genetic data for scientific research purposes, without obtaining additional
      consent will be allowed, if the specific conditions is met. The new Regulation
      has already fueled concerns among various stakeholders, owing to the challenges
      that may emerge when implementing the Regulation across the countries. Notably,
      the provided definition for pseudonymized data has been criticized because it
      leaves too much room for interpretations, and it might undermine the
      harmonization of the data protection across the countries.

PMID- 29187735
TI  - Mitochondrial genomes uncover the maternal history of the Pamir populations.
AB  - The Pamirs, among the world's highest mountains in Central Asia, are one of
      homelands with the most extreme high altitude for several ethnic groups. The
      settlement history of modern humans on the Pamirs remains still opaque. Herein,
      we have sequenced the mitochondrial DNA (mtDNA) genomes of 382 individuals
      belonging to eight populations from the Pamirs and the surrounding lowlands in
      Central Asia. We construct the Central Asian (including both highlanders and
      lowlanders) mtDNA haplogroup tree at the highest resolution. All the matrilineal
      components are assigned into the defined mtDNA haplogroups in East and West
      Eurasians. No basal lineages that directly emanate from the Eurasian founder
      macrohaplogroups M, N, and R are found. Our data support the origin of Central
      Asian being the result of East-West Eurasian admixture. The coalescence ages for
      more than 93% mtDNA lineages in Central Asians are dated after the last glacial
      maximum (LGM). The post-LGM and/or later dispersals/admixtures play dominant
      roles in shaping the maternal gene pool of Central Asians. More importantly, our
      analyses reveal the mtDNA heterogeneity in the Pamir highlanders, not only
      between the Turkic Kyrgyz and the Indo-European Tajik groups, but also among
      three highland Tajiks. No evidence supports positive selection or relaxation of
      selective constraints in the mtDNAs of highlanders as compared to that of
      lowlanders. Our results suggest a complex history for the peopling of Pamirs by
      multiple waves of migrations from various genetic resources during different time
      scales.

PMID- 29187737
TI  - The role of CNVs in the etiology of rare autosomal recessive disorders: the
      example of TRAPPC9-associated intellectual disability.
AB  - INTRODUCTION: A large number of genes involved in autosomal recessive forms of
      intellectual disability (ID) were identified over the past few years through
      whole-exome sequencing (WES) or whole-genome sequencing in consanguineous
      families. Disease-associated variants in TRAPPC9 were reported in eight multiplex
      consanguineous sibships from different ethnic backgrounds, and led to the
      delineation of the phenotype. Affected patients have microcephaly, obesity,
      normal motor development, severe ID, and language impairment and brain anomalies.
      PATIENTS: We report six new patients recruited through a national collaborative
      network. RESULTS: In the two patients heterozygous for a copy-number variation
      (CNV), the phenotype was clinically relevant with regard to the literature, which
      prompted to sequence the second allele, leading to identification of disease
      associated variants in both. The third patient was homozygote for an intragenic
      TRAPPC9 CNV. The phenotype of the patients reported was concordant with the
      literature. Recent reports emphasized the role of CNVs in the etiology of rare
      recessive disorders. CONCLUSION: This study demonstrates that CNVs significantly
      contribute to the mutational spectrum of TRAPPC9 gene, and also confirms the
      interest of combining WES with CNV analysis to provide a molecular diagnosis to
      patients with rare Mendelian disorders.

PMID- 29187738
TI  - Signaling mechanisms that regulate ex vivo survival of human acute myeloid
      leukemia initiating cells.

PMID- 29187739
TI  - Super-radiance reveals infinite-range dipole interactions through a nanofiber.
AB  - Atoms interact with each other through the electromagnetic field, creating
      collective states that can radiate faster or slower than a single atom, i.e.,
      super- and sub-radiance. When the field is confined to one dimension it enables
      infinite-range atom-atom interactions. Here we present the first report of
      infinite-range interactions between macroscopically separated atomic dipoles
      mediated by an optical waveguide. We use cold 87Rb atoms in the vicinity of a
      single-mode optical nanofiber (ONF) that coherently exchange evanescently coupled
      photons through the ONF mode. In particular, we observe super-radiance of a few
      atoms separated by hundreds of resonant wavelengths. The same platform allows us
      to measure sub-radiance, a rarely observed effect, presenting a unique tool for
      quantum optics. This result constitutes a proof of principle for collective
      behavior of macroscopically delocalized atomic states, a crucial element for new
      proposals in quantum information and many-body physics.

PMID- 29187740
TI  - Observed positive vegetation-rainfall feedbacks in the Sahel dominated by a
      moisture recycling mechanism.
AB  - Classic, model-based theory of land-atmosphere interactions across the Sahel
      promote positive vegetation-rainfall feedbacks dominated by surface albedo
      mechanism. However, neither the proposed positive vegetation-rainfall feedback
      nor its underlying albedo mechanism has been convincingly demonstrated using
      observational data. Here, we present observational evidence for the region's
      proposed positive vegetation-rainfall feedback on the seasonal to interannual
      time scale, and find that it is associated with a moisture recycling mechanism,
      rather than the classic albedo-based mechanism. Positive anomalies of remotely
      sensed vegetation greenness across the Sahel during the late and post-monsoon
      periods favor enhanced evapotranspiration, precipitable water, convective
      activity and rainfall, indicative of amplified moisture recycling. The identified
      modest low-level cooling and anomalous atmospheric subsidence in response to
      positive vegetation greenness anomalies are counter to the responses expected
      through the classic vegetation-albedo feedback mechanism. The observational
      analysis further reveals enhanced dust emissions in response to diminished Sahel
      vegetation growth, potentially contributing to the positive vegetation-rainfall
      feedback.

PMID- 29187742
TI  - Bone: DJ-1 orchestrates osteoclastogenesis.

PMID- 29187741
TI  - NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription.
AB  - Myosin VI (MVI) has been found to be overexpressed in ovarian, breast and
      prostate cancers. Moreover, it has been shown to play a role in regulating cell
      proliferation and migration, and to interact with RNA Polymerase II (RNAPII).
      Here, we find that backfolding of MVI regulates its ability to bind DNA and that
      a putative transcription co-activator NDP52 relieves the auto-inhibition of MVI
      to enable DNA binding. Additionally, we show that the MVI-NDP52 complex binds
      RNAPII, which is critical for transcription, and that depletion of NDP52 or MVI
      reduces steady-state mRNA levels. Lastly, we demonstrate that MVI directly
      interacts with nuclear receptors to drive expression of target genes, thereby
      suggesting a link to cell proliferation and migration. Overall, we suggest MVI
      may function as an auxiliary motor to drive transcription.

PMID- 29187743
TI  - Synaptic transmission: Closer encounters.

PMID- 29187744
TI  - It is a marathon rather than a sprint: an initial exploration of unmet needs and
      support preferences of caregivers of children with SCI.
AB  - STUDY DESIGN: Focus group study. OBJECTIVES: Explore unmet needs and support
      preferences of caregivers of youth with spinal cord injury (SCI). SETTING: One
      pediatric specialty rehabilitation hospital system in the United States. METHODS:
      Four focus groups were conducted with a convenience sample of 26 caregivers who
      were primarily mothers (96%) and married (65%), and had at least some college
      education (85%). Children living with SCI were on average 12.8 years old (SD =
      3.3, 8-18). The average age of injury was 4.7 years (SD = 4.4, 0-16.2); mean
      injury duration was 8.2 years (SD = 3.9, 2-16); 77% had paraplegia; and 58% were
      male. Focus groups were digitally recorded, transcribed verbatim, and coded using
      thematic analysis and NVivo. RESULTS: Qualitative data highlighted caregiver
      perspectives on unmet needs relating to two phases of care: acute and
      rehabilitation vs. current life with SCI, and two kinds of stressors: those
      associated with SCI and care vs. those related to other areas of the caregivers'
      lives, especially their families. Caregivers described stressful interactions
      with care systems and community services, articulated several concerns regarding
      well-being of family members, and noted that both they and their children with
      SCI experienced isolation. Caregivers articulated preferences for additional
      support from professionals and peers. CONCLUSIONS: Data suggest the need for
      ongoing caregiver interventions and strengthened family-centered care systems,
      including professional assistance navigating health systems and peer support.
      Intervention development would benefit from further qualitative data collection
      with additional caregivers of youth with SCI, including multiple family members,
      and families from more diverse care settings.

PMID- 29187745
TI  - A latent structural analysis of health behaviors among people living with spinal
      cord injury.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To develop a latent structural
      model of health behaviors among people with spinal cord injury (SCI) that
      accounts for measurement of underlying factors and their association with
      demographic and injury-related variables. SETTING: The data were collected at a
      large specialty hospital and analyzed at a medical university in the Southeastern
      United States. METHODS: A total of 1871 participants with traumatic SCI of at
      least 1-year duration were included. Exploratory factor analysis (EFA) was used
      to identify the latent health behavior structures. Several key exogenous
      variables were also linked with the latent health behavior factors. RESULTS: Five
      latent health behavior factors were identified by the EFA with excellent model
      fit (root mean square error of approximation = 0.043). These latent factors
      included (1) medication non-compliance, (2) prescription medication and substance
      use, (3) smoking, (4) alcohol consumption, and (5) healthy lifestyle activities
      and participation. Sex, race/ethnicity, age, years since injury, and injury
      severity were all significantly associated with at least one latent health
      behavior factor. For instance, men scored higher in smoking and alcohol
      consumption, whereas women scored higher in prescription medication and substance
      use. Non-whites scored higher on the medication non-compliance dimension and
      lower on the healthy lifestyle activities and participation dimension.
      CONCLUSIONS: Utilization of latent health behavior factors provides more stable
      and comprehensive composite scores than does a single observed health behavior
      indicator. There are important differences in behaviors based on individual
      characteristics.

PMID- 29187747
TI  - Time from US Food and Drug Administration approval to publication of data for
      cancer drugs: a comparison of first and subsequent approvals.

PMID- 29187746
TI  - Genome-wide haplotype-based association analysis of major depressive disorder in
      Generation Scotland and UK Biobank.
AB  - Genome-wide association studies using genotype data have had limited success in
      the identification of variants associated with major depressive disorder (MDD).
      Haplotype data provide an alternative method for detecting associations between
      variants in weak linkage disequilibrium with genotyped variants and a given trait
      of interest. A genome-wide haplotype association study for MDD was undertaken
      utilising a family-based population cohort, Generation Scotland: Scottish Family
      Health Study (n = 18,773), as a discovery cohort with UK Biobank used as a
      population-based replication cohort (n = 25,035). Fine mapping of haplotype
      boundaries was used to account for overlapping haplotypes potentially tagging the
      same causal variant. Within the discovery cohort, two haplotypes exceeded genome
      wide significance (P < 5 * 10-8) for an association with MDD. One of these
      haplotypes was nominally significant in the replication cohort (P < 0.05) and was
      located in 6q21, a region which has been previously associated with bipolar
      disorder, a psychiatric disorder that is phenotypically and genetically
      correlated with MDD. Several haplotypes with P < 10-7 in the discovery cohort
      were located within gene coding regions associated with diseases that are
      comorbid with MDD. Using such haplotypes to highlight regions for sequencing may
      lead to the identification of the underlying causal variants.

PMID- 29187749
TI  - Hyponatremia in patients receiving parenteral nutrition: the importance of
      correcting serum sodium for total proteins. The role of the composition of
      parenteral nutrition in the development of hyponatremia.
AB  - BACKGROUND/OBJECTIVES: Hyponatremia is the most common electrolyte disorder, and
      is associated with high-morbimortality rates. The true prevalence of hyponatremia
      in patients on parenteral nutrition (PN) is unknown, and the relationship between
      PN composition and development of hyponatremia has yet to be studied.
      Hypoproteinemia, a common finding in patients receiving PN, induces an
      overestimation of serum sodium (SNa) levels, when using indirect electrolyte
      methodology. Thus, SNa should be corrected for serum total protein levels (TP).
      The objective was to accurately determine the prevalence of hyponatremia
      (indirect SNa corrected for PT) and evaluate the relationship between the
      composition of PN and the development of hyponatremia. SUBJECTS/METHODS: Medical
      records of 222 hospitalized patients receiving total PN during a 7-month period
      were reviewed. Composition of PN, indirect SNa-mmol/l-, and SNa corrected for TP
      (SNa-TP)-mmol/l-, both upon initiation and during PN administration, were
      analyzed. RESULTS: Hyponatremia (SNa < 135 mmol/l) was present in 81% of subjects
      when SNa was corrected for TP, vs. 43% without correction (p = 0.001). In total
      64% of patients that were eunatremic upon initiation of PN developed hyponatremia
      during PN administration, as detected by SNa-TP, vs. 28% as detected by
      uncorrected SNa (p < 0.001). There were no significant differences in volume,
      osmolarity, sodium or total osmols administered in PN between patients who
      developed hyponatremia and those who remained eunatremic. CONCLUSIONS: A majority
      of patients receiving PN present hyponatremia, when indirect SNa levels are
      corrected for TP. The development of hyponatremia during PN is not related to the
      composition of the PN.

PMID- 29187750
TI  - Beverage consumption in Australian children.
AB  - BACKGROUND/OBJECTIVES: While beverages are an important dietary source of water
      and some essential nutrients, consumption of sweet beverages has increasingly
      been linked to adverse health outcomes. Currently there is a paucity of
      longitudinal consumption data on beverage consumption in Australian children.
      SUBJECTS/METHODS: The Longitudinal Study of Australian Children has run
      biennially since 2004. Twenty four-hour recall data collected over 6 waves from
      the birth cohort (aged 0-1 year at baseline) was analysed and demographics were
      assessed for associations. RESULTS: Five thousand one hundred and seven children
      participated at baseline, with a 71-90% retention of participants at each wave.
      Water consumption remained consistent with age over time, with more than 90%
      consuming more than one glass in the last 24-h. Proportions of fruit juice
      consumers decreased overall. Soft drink and cordial consumer proportions
      increased from 1% (0-1 year), to 28% (2 years) and 43% (10 years). Between 2 and
      10 years, proportions of consumption of full-cream milk decreased by 8% and for
      skim milk this proportion increased by 51%. High proportions of consumers of soft
      drink/cordial was significantly associated with older children, males, children
      with a medical condition, living in a rural area, low socio-economic status and
      Indigenous Australians. CONCLUSIONS: Water consumption remained consistently high
      across the ages, while fruit juice was commonly introduced into the diet early
      childhood. While proportions of fruit juice consumers decreased after the age of
      2 years, proportions of soft drink consumers increased. The findings from this
      study should assist with surveillance data and inform policy and interventions
      aimed at reducing consumption of sweet beverages.

PMID- 29187748
TI  - Genome-wide association study of subcortical brain volume in PTSD cases and
      trauma-exposed controls.
AB  - Depending on the traumatic event, a significant fraction of trauma survivors
      subsequently develop PTSD. The additional variability in PTSD risk is expected to
      arise from genetic susceptibility. Unfortunately, several genome-wide association
      studies (GWAS) have failed to identify a consistent genetic marker for PTSD. The
      heritability of intermediate phenotypes such as regional brain volumes is often
      80% or higher. We conducted a GWAS of subcortical brain volumes in a sample of
      recent military veteran trauma survivors (n = 157), grouped into PTSD (n = 66)
      and non-PTSD controls (n = 91). Covariates included PTSD diagnosis, sex,
      intracranial volume, ancestry, childhood trauma, SNP*PTSD diagnosis, and
      SNP*childhood trauma. We identified several genetic markers in high linkage
      disequilibrium (LD) with rs9373240 (p = 2.0 * 10-7, FDR q = 0.0375) that were
      associated with caudate volume. We also observed a significant interaction
      between rs9373240 and childhood trauma (p-values = 0.0007-0.002), whereby
      increased trauma exposure produced a stronger association between SNPs and
      increased caudate volume. We identified several SNPs in high LD with rs34043524,
      which is downstream of the TRAM1L1 gene that were associated with right lateral
      ventricular volume (p = 1.73 * 10-7; FDR q = 0.032) and were also associated with
      lifetime alcohol abuse or dependence (p = 2.49 * 10-7; FDR q = 0.0375). Finally,
      we identified several SNPs in high LD with rs13140180 (p = 2.58 * 10-7; FDR q =
      .0016), an intergenic region on chromosome 4, and several SNPs in the TMPRSS15
      associated with right nucleus accumbens volume (p = 2.58 * 10-7; FDR q = 0.017).
      Both TRAM1L1 and TMPRSS15 have been previously implicated in neuronal function.
      Key results survived genome-wide multiple-testing correction in our sample.
      Leveraging neuroimaging phenotypes may offer a shortcut, relative to clinical
      phenotypes, in mapping the genetic architecture and neurobiological pathways of
      PTSD.

PMID- 29187751
TI  - Demonstration of chemistry at a point through restructuring and catalytic
      activation at anchored nanoparticles.
AB  - Metal nanoparticles prepared by exsolution at the surface of perovskite oxides
      have been recently shown to enable new dimensions in catalysis and energy
      conversion and storage technologies owing to their socketed, well-anchored
      structure. Here we show that contrary to general belief, exsolved particles do
      not necessarily re-dissolve back into the underlying perovskite upon oxidation.
      Instead, they may remain pinned to their initial locations, allowing one to
      subject them to further chemical transformations to alter their composition,
      structure and functionality dramatically, while preserving their initial spatial
      arrangement. We refer to this concept as chemistry at a point and illustrate it
      by tracking individual nanoparticles throughout various chemical transformations.
      We demonstrate its remarkable practical utility by preparing a nanostructured
      earth abundant metal catalyst which rivals platinum on a weight basis over
      hundreds of hours of operation. Our concept enables the design of compositionally
      diverse confined oxide particles with superior stability and catalytic
      reactivity.

PMID- 29187752
TI  - Inhibiting Rho kinase promotes goal-directed decision making and blocks habitual
      responding for cocaine.
AB  - The prelimbic prefrontal cortex is necessary for associating actions with their
      consequences, enabling goal-directed decision making. We find that the strength
      of action-outcome conditioning correlates with dendritic spine density in
      prelimbic cortex, suggesting that new action-outcome learning involves dendritic
      spine plasticity. To test this, we inhibited the cytoskeletal regulatory factor
      Rho kinase. We find that the inhibitor fasudil enhances action-outcome memory,
      resulting in goal-directed behavior in mice that would otherwise express stimulus
      response habits. Fasudil transiently reduces prelimbic cortical dendritic spine
      densities during a period of presumed memory consolidation, but only when paired
      with new learning. Fasudil also blocks habitual responding for cocaine, an effect
      that persists over time, across multiple contexts, and depends on actin
      polymerization. We suggest that Rho kinase inhibition promotes goal-oriented
      action selection by augmenting the plasticity of prelimbic cortical dendritic
      spines during the formation of new action-outcome memories.

PMID- 29187753
TI  - Subchronic olanzapine exposure leads to increased expression of myelination
      related genes in rat fronto-medial cortex.
AB  - Schizophrenia is a psychotic disorder with severe and disabling symptoms, such as
      hallucinations, delusions, blunted affect and social withdrawal. The
      neuropathology remains elusive, but disturbances in immunity-related processes,
      neuronal connectivity and myelination have consistently been linked to
      schizophrenia. Antipsychotic drugs can be efficient in reducing symptoms, acting
      primarily on the dopamine system, but additional biological targets are likely to
      exist. Here we have screened for novel mechanisms of action in an animal model,
      using adult rats exposed to long-acting olanzapine, achieving stable and
      clinically relevant antipsychotic drug concentrations. By microarray-based
      examination of global gene expression in the fronto-medial cortex, at the single
      gene- and gene-set level, we observed downregulation of two neuropeptide-encoding
      genes, Vgf and Cort (fold change -1,25 and -1,48, respectively) in response to
      olanzapine exposure. Furthermore, we demonstrated significant upregulation of
      five out of ~2000 GO predefined gene sets after olanzapine exposure. Strikingly,
      all were linked to myelination and oligodendrocyte development; "Ensheathment of
      neurons", "Axon ensheathment", "Myelination", "Myelin sheath" and
      "Oligodendrocyte development" (FDR-values < 25). Sixteen of the leading edge
      genes in these gene sets were analysed independently by qPCR, of which 11 genes
      displayed significant upregulation, including Plp1, Mal, Mag and Cnp (fold
      change: 1,30, 1,50, 1,30 and 1,15, respectively). Several of the upregulated
      genes (e.g. MAG, MAL and CNP) have previously been reported as downregulated in
      post-mortem brain samples from schizophrenia patients. Although caution needs to
      be taken when extrapolating results from animal studies to humans, the data
      suggest a role for olanzapine in alleviating myelination-related dysfunction in
      schizophrenia.

PMID- 29187754
TI  - Fluoxetine treatment is effective in a rat model of childhood-induced post
      traumatic stress disorder.
AB  - Although selective serotonin reuptake inhibitors (SSRIs) are first-line treatment
      for post-traumatic stress disorder (PTSD) patients, their therapeutic efficacy is
      limited. Childhood adversities are considered a risk factor for developing PTSD
      in adulthood but may trigger PTSD without additional trauma in some individuals.
      Nevertheless, just as childhood is considered a vulnerable period it may also be
      an effective period for preventive treatment. Using a rat model of childhood
      induced PTSD, pre-pubertal stress (juvenile stress, JVS), we compared the
      therapeutic effects of fluoxetine and examined the effectiveness of 1 month of
      fluoxetine treatment following JVS and into adulthood compared to treatment in
      adulthood. Since not all individuals develop PTSD following a trauma, comparing
      only group means is not the adequate type of analysis. We employed a behavioral
      profiling approach, which analyzes individual differences compared to the normal
      behavior of a control group. Animals exposed to JVS exhibited a higher proportion
      of affected animals as measured using the elevated plus maze 8 weeks after JVS.
      Fluoxetine treatment following the JVS significantly decreased the proportion of
      affected animals as measured in adulthood. Fluoxetine treatment in adulthood was
      not effective. The results support the notion that childhood is not only a
      vulnerable period but also an effective period for preventive treatment.

PMID- 29187756
TI  - Pilot study on microvascular anastomosis: performance and future educational
      prospects.
AB  - The introduction of microvascular free flaps has revolutionised modern
      reconstructive surgery. Unfortunately, access to training opportunities at
      standardised training courses is limited and expensive. We designed a pilot study
      on microvascular anastomoses with the aim of verifying if a short course, easily
      reproducible, could transmit microvascular skills to participants; if the chosen
      pre-test was predictive of final performance; and if age could influence the
      outcome. A total of 30 participants (10 students, 10 residents and 10 surgeons)
      without any previous microvascular experience were instructed and tested during a
      single 3 to 5 hour course. The two microanastomoses evaluated were the first ever
      performed by each participant. More than the half of the cohort was able to
      produce both patent microanastomoses in less than 2 hours; two-thirds of the
      attempted microanastomoses were patent. The pretest predicted decent scores from
      poor performances with a sensitivity of 61.5%, specificity of 100%, positive
      predictive value of 100% and negative predictive value of 40%. Students and
      residents obtained significantly higher scores than surgeons. Since our course
      model is short, cost-effective and highly reproducible, it could be introduced
      and implemented anywhere as an educational prospect for preselecting young
      residents showing talent and natural predisposition and having ambitions towards
      microvascular reconstructive surgery.

PMID- 29187755
TI  - A mouse model of the schizophrenia-associated 1q21.1 microdeletion syndrome
      exhibits altered mesolimbic dopamine transmission.
AB  - 1q21.1 hemizygous microdeletion is a copy number variant leading to eightfold
      increased risk of schizophrenia. In order to investigate biological alterations
      induced by this microdeletion, we generated a novel mouse model (Df(h1q21)/+) and
      characterized it in a broad test battery focusing on schizophrenia-related
      assays. Df(h1q21)/+ mice displayed increased hyperactivity in response to
      amphetamine challenge and increased sensitivity to the disruptive effects of
      amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition. Probing
      of the direct dopamine (DA) pathway using the DA D1 receptor agonist SKF-81297
      revealed no differences in induced locomotor activity compared to wild-type mice,
      but Df(h1q21)/+ mice showed increased sensitivity to the DA D2 receptor agonist
      quinpirole and the D1/D2 agonist apomorphine. Electrophysiological
      characterization of DA neuron firing in the ventral tegmental area revealed more
      spontaneously active DA neurons and increased firing variability in Df(h1q21)/+
      mice, and decreased feedback reduction of DA neuron firing in response to
      amphetamine. In a range of other assays, Df(h1q21)/+ mice showed no difference
      from wild-type mice: gross brain morphology and basic functions such as reflexes,
      ASR, thermal pain sensitivity, and motor performance were unaltered. Similarly,
      anxiety related measures, baseline prepulse inhibition, and seizure threshold
      were unaltered. In addition to the central nervous system-related phenotypes,
      Df(h1q21)/+ mice exhibited reduced head-to tail length, which is reminiscent of
      the short stature reported in humans with 1q21.1 deletion. With aspects of both
      construct and face validity, the Df(h1q21)/+ model may be used to gain insight
      into schizophrenia-relevant alterations in dopaminergic transmission.

PMID- 29187758
TI  - Cochlear obliteration following a translabyrinthine approach and its implications
      in cochlear implantation.
AB  - The most frequent sequelae following a translabyrinthine approach for vestibular
      schwannoma resection is complete hearing loss on the affected side. Such patients
      could benefit from a cochlear implant, provided that two essential requisites are
      met before surgery: a preserved cochlear nerve and a patent cochlea to
      accommodate the electrode array. The goal of our study is to determine the
      prevalence and extent of cochlear ossification following a translabyrinthine
      approach. Postoperative MRI of 41 patients were retrospectively reviewed.
      Patients were classified according to the degree of cochlear obliteration into
      three groups (patent cochlea, partially obliterated cochlea and totally
      obliterated cochlea). The interval between surgery and the first MRI was studied
      as well as its relationship with the rate of cochlear ossification. At first
      postoperative MRI (mean interval of 20 months), 78% of patients showed some
      degree of cochlear ossification. Differences were found in the time interval
      between surgery and first MRI for each group, showing a smaller interval of time
      the patent cochlea group (p > 0.05). When MRI was performed before the first year
      after surgery, a larger rate of patent cochlea was found (p > 0.05). The present
      study suggests that cochlear ossification is a time-depending process, whose
      grounds are still to be defined.

PMID- 29187760
TI  - The EXIT (ex-utero intrapartum treatment) procedure - from the paediatric ENT
      perspective.
AB  - The main principle of the EXIT procedure is to maintain uteroplacental
      circulation with neonatal anaesthesia by controlled uterine hypotonia. This
      enables securing the foetal airways and decompress or resect large neck and
      mediastinal foetal masses. The authors present their experience with use of the
      EXIT procedure in 7 foetuses in whom evaluation and management of the airways
      were performed. In 4 patients, the neck mass was surgically removed in the
      neonatal period, in 1 the propranolol treatment was introduced. Two newborns died
      shortly after the EXIT procedure. The EXIT procedure allows the paediatric
      otolaryngologist to provide airway patency of newborns during delivery. Both
      ultrasound and MR imaging are crucial in the prenatal assessment of foetal head
      and neck masses. Their application in the evaluation of any foetal anomaly is
      essential for proper prognosis and treatment. Maternal monitoring for
      complications such as polyhydramnios and preterm labour are important in planning
      and desirability of the EXIT procedure.

PMID- 29187761
TI  - Gold nanocage-based lateral flow immunoassay for immunoglobulin G.
AB  - The authors describe a gold nanocage-based lateral flow strip biosensor (LFSB)
      for low-cost and sensitive detection of IgG. This protein was used as a model
      analyte to demonstrate the proof-of-concept. The method combines the unique
      optical properties of gold nanocages (GNCs) with highly efficient chromatographic
      separation. A sandwich-type of immunoreactions occurs on the GNC-based LFSB which
      has the attractive features of avoiding multiple incubation, separation, and
      washing steps. The captured GNCs on the purple test zone and control zone of the
      biosensor are producing characteristic purple bands, and this enables IgG even to
      be visually detected. Quantitatation was accomplished by reading the intensities
      of the bands with a portable strip reader. The LFSB fabrication and assay
      parameters were optimized. The biosensor displays a linear response in the 0.5 to
      50 ng.mL-1 IgG concentration range, and it has a 15 min assay time. The detection
      limit is 0.1 ng.mL-1 of IgG, which is 2.5 times lower than that when using a gold
      nanoparticle-based LFSB. In our perception, this assay has a wide potential for
      the detection of other proteins and species for which respective antibodies are
      available.

PMID- 29187762
TI  - Formation of potentially toxic carbonyls during oxidation of triolein in the
      presence of alimentary antioxidants.
AB  - Abstract: A relation between oil uptake and cancer as well as induction of
      hepatic inflammation was shown earlier. It is discussed that the main oil
      oxidation products-hydroperoxides and carbonyls-might be the reason for the
      mentioned diseases. In this manuscript quantitative determination of aldehydes
      which are formed during oxidation of triolein-as a model substance-using the
      Rancimat 679 is described. The oxidation of 11 g of triolein is carried out at
      120  degrees C sparging air with a flow of 20 dm3/h for 10 h. A series of
      aliphatic aldehydes starting from hexanal to decanal as well as decenal was
      identified by LC-MS/MS and quantified as DNPH derivatives. In addition, the total
      amount of carbonyls was determined. Based on the calibration with hexanal, all
      other dominant substances were in the similar concentration range with maximum
      concentrations of 1.6 umol/cm3 of hexanal, 2.3 umol/cm3 of heptanal, 2.5 umol/cm3
      of octanal, 3.2 umol/cm3 of nonanal, 4.0 umol/cm3 of decanal after 6 h. The total
      amount of carbonyls reached a maximum after 6 h being 27 umol/cm3 for triolein
      without antioxidant. The results of this investigation will be a basis for
      further toxicological studies on oxidized oils. Graphical abstract: 

PMID- 29187764
TI  - Rasch Analyses of Very Low Food Security among Households and Children in the
      Three City Study.
AB  - The longitudinal Three City Study of low-income families with children measures
      food hardships using fewer questions and some different questions from the
      standard U.S. instrument for measuring food security, the Household Food Security
      Survey Module (HFSSM) in the Current Population Survey (CPS). We utilize a Rasch
      measurement model to identify thresholds of very low food security among
      households and very low food security among children in the Three City Study that
      are comparable to thresholds from the HFSSM. We also use the Three City Study to
      empirically investigate the determinants of food insecurity and of these specific
      food insecurity outcomes, estimating a multivariate behavioral Rasch model that
      is adapted to address longitudinal data. The estimation results indicate that
      participation in the Supplemental Nutrition Assistance Program and the Temporary
      Assistance for Needy Families program reduce food insecurity, while poverty and
      disability among caregivers increase it. Besides its longitudinal structure, the
      Three City Study measures many more characteristics about households than the
      CPS. Our estimates reveal that financial assistance through social networks and a
      household's own financial assets reduce food insecurity, while its outstanding
      loans increase insecurity.

PMID- 29187763
TI  - Race, Marital History, and Risks for Stroke in US Older Adults.
AB  - Stroke is among the leading causes of disability and death in the United States,
      and racial differences are greater for stroke than for all other major chronic
      diseases. Considering the equally sizeable racial disparities in marital life and
      associated risks across adulthood, the current study hypothesizes that black
      white differences in marital history play an important role in the large racial
      inequalities in the incidence of stroke. The major objective are to (i)
      demonstrate how marital history is associated with the incidence of stroke, (ii)
      examine how marital factors mediate and/or moderate racial disparities in stroke,
      and (iii) examine the factors that may explain the associations. Using
      retrospective and prospective data from the Health and Retirement Study (n =
      23,289), the results show that non-Hispanic (NH) blacks have significantly higher
      rates of marital instability, greater numbers of health-risk factors, and
      substantially higher rates of stroke compared with NH whites. Contrary to the
      cumulative disadvantage hypothesis, findings from discrete-time-hazard models
      show that the effects of marital history are more pronounced for NH whites than
      for NH blacks. Risks for stroke were significantly higher in NH whites who were
      currently divorced, remarried, and widowed, as well as in those with a history of
      divorce or widowhood, compared with NH whites who were continuously married. In
      NH blacks, risks for stroke were elevated only in those who had either never
      married or had been widowed-with no significant risks attributable to divorce.
      The potential mechanisms underlying the associations are assessed, and the
      implications of the findings are discussed.

PMID- 29187765
TI  - Effect of Land Use, Seasonality, and Hydrometeorological Conditions on the K+
      Concentration-Discharge Relationship During Different Types of Floods in
      Carpathian Foothills Catchments (Poland).
AB  - The purpose of the study was to determine the role of land use, seasonality, and
      hydrometeorological conditions on the relationship between stream water potassium
      (K+) concentration and discharge during different types of floods-short- and long
      duration rainfall floods as well as snowmelt floods on frozen and thawed soils.
      The research was conducted in small catchments (agricultural, woodland, mixed
      use) in the Carpathian Foothills (Poland). In the woodland catchment, lower K+
      concentrations were noted for each given specific runoff value for summer
      rainfall floods versus snowmelt floods (seasonal effect). In the agricultural and
      mixed-use catchments, the opposite was true due to their greater ability to flush
      K+ out of the soil in the summer. In the stream draining woodland catchment,
      higher K+ concentrations occurred during the rising limb than during the falling
      limb of the hydrograph (clockwise hysteresis) for all flood types, except for
      snowmelt floods with the ground not frozen. In the agricultural catchment,
      clockwise hystereses were produced for short- and long-duration rainfall floods
      caused by high-intensity, high-volume rainfall, while anticlockwise hystereses
      were produced for short- and long-duration rainfall floods caused by low
      intensity, low-volume rainfall as well as during snowmelt floods with the soil
      frozen and not frozen. In the mixed-use catchment, the hysteresis direction was
      also affected by different lag times for water reaching stream channels from
      areas with different land use. K+ hystereses for the woodland catchment were more
      narrow than those for the agricultural and mixed-use catchments due to a smaller
      pool of K+ in the woodland catchment. In all streams, the widest hystereses were
      produced for rainfall floods preceded by a long period without rainfall.

PMID- 29187766
TI  - Perceptions and Experiences of an Attachment-Based Intervention for Parents
      Troubled by Intimate Partner Violence.
AB  - It is known that intimate partner violence (IPV) negatively affects both parental
      capacity and children's well-being, but few studies have focused on the
      experiences of those taking part in family interventions focused on IPV. In this
      study, 26 parents (16 mothers and 10 fathers) with a history of IPV participated
      in focus groups concerning their attachment-based group intervention experience
      in the program Parenting and Violence. The transcripts, subjected to thematic
      analysis, showed that participants experienced the intervention as supportive and
      confirming of their role as parents. Parents described feeling more in control,
      more self-confident, more skilled in communicating, and more able to provide
      security for their children. However, they also expressed a need for continuing
      support to maintain their improved parenting strategies.

PMID- 29187767
TI  - Triads in Equine-Assisted Social Work Enhance Therapeutic Relationships with Self
      Harming Adolescents.
AB  - Despite an increasing number of studies, there is still a lack of knowledge about
      the unique features that underlie the process in equine assisted social work
      (EASW). This study aimed to reveal, through qualitative methods, the dyads within
      the triad that become stronger during the process of EASW, as well as the effect
      of the participation of the horse on the relationship between the counselor and
      client. Data were collected through in-depth interviews with nine female self
      harming clients aged 15-21 years and eight staff members. The interviews,
      together with video-recorded human-horse interactions with three staff members
      and four clients were analyzed, resulting in additional issues answered by these
      three staff members and four clients in a second interview. Critical dialogues
      between patterns and fragmentations in the narratives and video-recordings, as
      well as a dialogue with the participants while they were viewing videos of their
      own EASW sessions, led to the conclusion that adding a horse qualitatively
      changes therapeutic relationships in EASW. The different triads consist of
      different liaisons between actors in the triad, giving rise to unique
      combinations. The quality of the relationships depends on both the staff and the
      clients' attachment orientations. Further research is needed to investigate how
      the degree of emotional connection to the horse affects the impact that horses
      have on triads in EASW.

PMID- 29187768
TI  - Barium and Radium Complexation with Ethylenediaminetetraacetic Acid in Aqueous
      Alkaline Sodium Chloride Media.
AB  - The speciation of Ra2+ and Ba2+ with EDTA was investigated at 25  degrees C in
      aqueous alkaline NaCl media as a function of ionic strength (0.2-2.5 mol.L-1) in
      two pH regions where the EDTA4- and HEDTA3- species dominate. The stability
      constants for the formation of the [BaEDTA]2- and [RaEDTA]2- complexes were
      determined using an ion exchange method. Barium-133 and radium-226 were used as
      radiotracers and their concentrations in the aqueous phase were measured using
      liquid scintillation counting and gamma spectrometry, respectively. The specific
      ion interaction theory (SIT) was used to account for [NaEDTA]3- and [NaHEDTA]2-
      complex formation, and used to extrapolate the logarithms of the apparent
      stability constants (log10K) to zero ionic strength (BaEDTA2-: 9.86 +/- 0.09;
      RaEDTA2-: 9.13 +/- 0.07) and obtain the Ba2+ and Ra2+ ion interaction parameters:
      [epsilon(Na+, BaEDTA2-) = - (0.03 +/- 0.11); epsilon(Na+, RaEDTA2-) = - (0.10 +/-
      0.11)]. It was found that in the pH region where HEDTA3- dominates, the reaction
      of Ba2+ or Ra2+ with the HEDTA3- ligand also results in the formation of the
      BaEDTA2- and RaEDTA2- complexes (as it does in the region where the EDTA4- ligand
      dominates) with the release of a proton. Comparison of the ion interaction
      parameters of Ba2+ and Ra2+ strongly indicates that both metal ions and their
      EDTA complexes have similar activity coefficients and undergo similar short-range
      interactions in aqueous NaCl media.

PMID- 29187769
TI  - Adolescent Sexual Behavior Research: Perspectives of Investigators, IRB Members,
      and IRB Staff about Risk Categorization and IRB Approval.

PMID- 29187770
TI  - Classification of micro-CT images using 3D characterization of bone canal
      patterns in human osteogenesis imperfecta.
AB  - Few studies have analyzed the microstructural properties of bone in cases of
      Osteogenenis Imperfecta (OI), or 'brittle bone disease'. Current approaches
      mainly focus on bone mineral density measurements as an indirect indicator of
      bone strength and quality. It has been shown that bone strength would depend not
      only on composition but also structural organization. This study aims to
      characterize 3D structure of the cortical bone in high-resolution micro CT
      images. A total of 40 bone fragments from 28 subjects (13 with OI and 15 healthy
      controls) were imaged using micro tomography using a synchrotron light source
      (SRMUCT). Minkowski functionals - volume, surface, curvature, and Euler
      characteristics - describing the topological organization of the bone were
      computed from the images. The features were used in a machine learning task to
      classify between healthy and OI bone. The best classification performance (mean
      AUC - 0.96) was achieved with a combined 4-dimensional feature of all Minkowski
      functionals. Individually, the best feature performance was seen using curvature
      (mean AUC - 0.85), which characterizes the edges within a binary object. These
      results show that quantitative analysis of cortical bone microstructure, in a
      computer-aided diagnostics framework, can be used to distinguish between healthy
      and OI bone with high accuracy.

PMID- 29187771
TI  - Who are Your Joneses? Socio-Specific Income Inequality and Trust.
AB  - Trust is a good approach to explain the functioning of markets, institutions or
      society as a whole. It is a key element in almost every commercial transaction
      over time and might be one of the main explanations of economic success and
      development. Trust diminishes the more we perceive others to have economically
      different living realities. In most of the relevant contributions, scholars have
      taken a macro perspective on the inequality-trust linkage, with an aggregation of
      both trust and inequality on a country level. However, patterns of within-country
      inequality and possibly influential determinants, such as perception and
      socioeconomic reference, remained undetected. This paper offers the opportunity
      to look at the interplay between inequality and trust at a more refined level. A
      measure of (generalized) trust emerges from ESS 5 survey which asks "...generally
      speaking, would you say that most people can be trusted, or that you can't be too
      careful in dealing with people?". With the use of 2009 EU-SILC data, measurements
      of income inequality are developed for age-specific groups of society in 22
      countries. A sizable variation in inequality measures can be noticed. Even in low
      inequality countries, like Sweden, income imbalances within certain age groups
      have the potential to undermine social trust.

PMID- 29187772
TI  - Fearful Faces do Not Lead to Faster Attentional Deployment in Individuals with
      Elevated Psychopathic Traits.
AB  - In the current study, a gaze-cueing experiment (similar to Dawel et al. 2015) was
      conducted in which the predictivity of a gaze-cue was manipulated (non-predictive
      vs highly predictive). This was done to assess the degree to which individuals
      with elevated psychopathic traits can use contextual information (i.e., the
      predictivity of the cue). Psychopathic traits were measured with the Self-Report
      Psychopathy Scale-Short Form (SRP-SF) in a mixed sample (undergraduate students
      and community members). Results showed no group difference in reaction times
      between high and non-predictive cueing blocks, suggesting that individuals with
      elevated psychopathic traits can indeed use contextual information when it is
      relevant. In addition, we observed that fearful facial expressions did not lead
      to a change in reaction times in individuals with elevated psychopathic traits,
      whereas individuals with low psychopathic traits showed speeded responses when
      confronted with a fearful face, compared to a neutral face. This suggests that
      fearful faces do not lead to faster attentional deployment in individuals with
      elevated psychopathic traits.

PMID- 29187773
TI  - Phase Behavior of Poly(3-hexylthiophene-2,5-diyl).
AB  - The phase behavior of many conjugated polymers is rich with both crystalline and
      liquid crystalline phases. Recent computational efforts have identified the
      isotropic-to-nematic transition temperature for polymers such as poly(3
      hexylthiophene-2,5-diyl) (P3HT). Herein, model predictions are combined with
      experimentally determined values of the equilibrium melting temperature as a
      function of chain length to provide the complete phase behavior for P3HT.
      Additionally, because a full description of the phase behavior requires proper
      accounting for the regioregularity of the chain, a thermodynamic relationship is
      derived to predict this behavior as a function of both chain length and
      regioregularity and the impact of regioregularity on the expected phase diagram
      is discussed.

PMID- 29187774
TI  - Effect of Superficial Gas Velocity on the Solid Temperature Distribution in Gas
      Fluidized Beds with Heat Production.
AB  - The hydrodynamics and heat transfer of cylindrical gas-solid fluidized beds for
      polyolefin production was investigated with the two-fluid model (TFM) based on
      the kinetic theory of granular flow (KTGF). It was found that the fluidized bed
      becomes more isothermal with increasing superficial gas velocity. This is mainly
      due to the increase of solids circulation and improvement in gas solid contact.
      It was also found that the average Nusselt number weakly depends on the gas
      velocity. The TFM results were qualitatively compared with simulation results of
      computational fluid dynamics combined with the discrete element model (CFD-DEM).
      The TFM results were in very good agreement with the CFD-DEM outcomes, so the TFM
      can be a reliable source for further investigations of fluidized beds especially
      large lab-scale reactors.

PMID- 29187775
TI  - Recent Developments at DG Competition: 2016/2017.
AB  - The Directorate General for Competition at the European Commission enforces
      competition law in the areas of antitrust, merger control, and state aids. This
      year's article provides first a general presentation of the role of the Chief
      Competition Economist's team and surveys the main achievements of the Directorate
      General for Competition over 2016/2017. The article then reviews the economic
      work undertaken in one merger case between Dow/DuPont, which raised specific
      issues related to innovation, as well as in an antitrust case on parity clauses
      related to Amazon e-books.

PMID- 29187776
TI  - Amoral, im/moral and dis/loyal: Children's moral status in child welfare.
AB  - This article is a discursive examination of children's status as knowledgeable
      moral agents within the Swedish child welfare system and in the widely used
      assessment framework BBIC. Departing from Fricker's concept of epistemic
      injustice, three discursive positions of children's moral status are identified:
      amoral, im/moral and dis/loyal. The findings show the undoubtedly moral child as
      largely missing and children's agency as diminished, deviant or rendered
      ambiguous. Epistemic injustice applies particularly to disadvantaged children
      with difficult experiences who run the risk of being othered, or positioned as
      reproducing or accommodating to the very same social problems they may be
      victimised by.

PMID- 29187777
TI  - Comments on "Coexistence of hidden chaotic attractors in a novel no-equilibrium
      system" (Nonlinear Dyn, doi:10.1007/s11071-016-3170-x).
AB  - In this comment, an enhancement of issue published in the paper "Coexistence of
      hidden chaotic attractors in a novel no-equilibrium system" (Nonlinear Dyn,
      doi:10.1007/s11071-016-3170-x) is addressed. We have shown that the proposed
      novel autonomous chaotic system can be extended to its fractional-order version
      where hidden attractors as well as other dynamical properties of the new no
      equilibrium system can be observed. A created MATLAB function for the new
      fractional-order no-equilibrium system is also presented.

PMID- 29187778
TI  - 30-years of experience with the cementless implanted Alloclassic total hip
      arthroplasty system-An ultra-long-term follow-up.
AB  - Objective: The aim of this study was to evaluate our long-term results with the
      Zweymuller hochgezogen and SL total hip arthroplasty system. This is the first
      study to provide a 30-year follow-up. Methods: We reviewed 186 Alloclassic stem
      systems (Zweymuller hochgezogen (112) and SL (74), implanted in 179 patients from
      1986 to 1987.Two different types of cementless acetabular components were
      used.143 patients had died over the last 30 years, so thirty out of 36 patients
      being still alive, with a mean follow-up of 29,48 years (SD 0,51), were contacted
      by telephone and evaluated radiologically and clinically. Our loss-to-follow up
      was 16,7%. The mean age at follow-up was 83,57 years (72,4-95,2; SD 6,77).
      Results: If the endpoint is defined as the removal of the stem for aseptic
      loosening (3 cases), the overall survival rate is 98,38%. If the endpoint is
      revision for any reason (27 cases), the survival rate is 85,48%. Eleven patients
      needed an exchange of head and liner. The mean time from implantation until
      change of head and liner was 21,44 years (SD 5,92).Most of the radiolucent lines
      and osteolytic zones were found in the proximal Gruen-zones 1 and 7 (69,7 and
      21,2%). Conclusion: After 30 years of monitoring we can state that the evaluated
      system is very reliable in primary and secondary THA.

PMID- 29187779
TI  - Shared Authentic Leadership in Research Teams: Testing a Multiple Mediation
      Model.
AB  - Research teams face complex leadership and coordination challenges. We propose
      shared authentic leadership (SAL) as a timely approach to addressing these
      challenges. Drawing from authentic and functional leadership theories, we posit a
      multiple mediation model that suggests three mechanisms whereby SAL influences
      team effectiveness: shared mental models (SMM), team trust, and team
      coordination. To test our hypotheses, we collected survey data on leadership and
      teamwork within 142 research teams that recently published an article in a peer
      reviewed management journal. The results indicate team coordination represents
      the primary mediating mechanism accounting for the relationship between SAL and
      research team effectiveness. While teams with high trust and SMM felt more
      successful and were more satisfied, they were less successful in publishing in
      high-impact journals. We also found the four SAL dimensions (i.e., self
      awareness, relational transparency, balanced processing, and internalized moral
      perspective) to associate differently with team effectiveness.

PMID- 29187780
TI  - The Skull of Epidolops ameghinoi from the Early Eocene Itaborai Fauna,
      Southeastern Brazil, and the Affinities of the Extinct Marsupialiform Order
      Polydolopimorphia.
AB  - The skull of the polydolopimorphian marsupialiform Epidolops ameghinoi is
      described in detail for the first time, based on a single well-preserved cranium
      and associated left and right dentaries plus additional craniodental fragments,
      all from the early Eocene (53-50 million year old) Itaborai fauna in southeastern
      Brazil. Notable craniodental features of E. ameghinoi include absence of a
      masseteric process, very small maxillopalatine fenestrae, a prominent pterygoid
      fossa enclosed laterally by a prominent ectopterygoid crest, an absent or tiny
      transverse canal foramen, a simple, planar glenoid fossa, and a postglenoid
      foramen that is immediately posterior to the postglenoid process. Most
      strikingly, the floor of the hypotympanic sinus was apparently unossified, a
      feature found in several stem marsupials but absent in all known crown
      marsupials. "Type II" marsupialiform petrosals previously described from Itaborai
      plausibly belong to E. ameghinoi; in published phylogenetic analyses, these
      petrosals fell outside (crown-clade) Marsupialia. "IMG VII" tarsals previously
      referred to E. ameghinoi do not share obvious synapomorphies with any crown
      marsupial clade, nor do they resemble those of the only other putative
      polydolopimorphians represented by tarsal remains, namely the argyrolagids. Most
      studies have placed Polydolopimorphia within Marsupialia, related to either
      Paucituberculata, or to Microbiotheria and Diprotodontia. However, diprotodonty
      almost certainly evolved independently in polydolopimorphians, paucituberculatans
      and diprotodontians, and Epidolops does not share obvious synapomorphies with any
      marsupial order. Epidolops is dentally specialized, but several morphological
      features appear to be more plesiomorphic than any crown marsupial. It seems
      likely Epidolops that falls outside Marsupialia, as do morphologically similar
      forms such as Bonapartherium and polydolopids. Argyrolagids differ markedly in
      their known morphology from Epidolops but share some potential apomorphies with
      paucituberculatans. It is proposed that Polydolopimorphia as currently recognised
      is polyphyletic, and that argyrolagids (and possibly other taxa currently
      included in Argyrolagoidea, such as groeberiids and patagoniids) are members of
      Paucituberculata. This hypothesis is supported by Bayesian non-clock phylogenetic
      analyses of a total evidence matrix comprising DNA sequence data from five
      nuclear protein-coding genes, indels, retroposon insertions, and morphological
      characters: Epidolops falls outside Marsupialia, whereas argyrolagids form a
      clade with the paucituberculatans Caenolestes and Palaeothentes, regardless of
      whether the Type II petrosals and IMG VII tarsals are used to score characters
      for Epidolops or not. There is no clear evidence for the presence of crown
      marsupials at Itaborai, and it is possible that the origin and early evolution of
      Marsupialia was restricted to the "Austral Kingdom" (southern South America,
      Antarctica, and Australia).

PMID- 29187781
TI  - Sparse Signal Recovery from a Mixture of Linear and Magnitude-Only Measurements.
AB  - We consider the problem of exact sparse signal recovery from a combination of
      linear and magnitude-only (phaseless) measurements. A k-sparse signal x ? C n is
      measured as r = Bx and y = |Cx|, where B ? C m1*n and C ? C m2*n are measurement
      matrices and | . | is the element-wise absolute value. We show that if max(2m1,
      1) + m2 >= 4k - 1, then a set of generic measurements are sufficient to recover
      every k-sparse x exactly, establishing the trade-off between the number of linear
      and magnitude-only measurements.

PMID- 29187783
TI  - The effect of micronutrient supplementation on active TB incidence early in HIV
      infection in Botswana.
AB  - Background: Coinfection with active tuberculosis (TB) is one of the leading
      causes of death in people living with HIV (PLWH) in Africa. This investigation
      explores the role of micronutrient supplementation in preventing active TB in
      PLWH. Methods: A randomized trial of nutritional supplementation was conducted
      among antiretroviral- naive (without previous antiretroviral treatment [ART]) HIV
      infected people in Botswana between 2004 and 2009. The study had a factorial
      design with four arms: the selenium (Se) alone arm, the multivitamins (MVT) alone
      arm that contained vitamin B complex and vitamins C and E, the combined Se+MVT
      group and the placebo group. Those participants with prior or current active TB
      were excluded, as were participants with advanced HIV disease (CD4 <250
      cells/MUL) or who had already qualified for ART. HIV-positive adults (N=878) were
      followed monthly for study pill dispensation, every 3 months for CD4 cell count
      and every 6 months for viral load during 24 months or until they were started on
      ART. Results: The participants' characteristics were not significantly different
      among the four groups at baseline. Supplementation with Se alone (hazard ratio
      =0.20, 95% confidence interval: 0.04, 0.95, P=0.043) and the two combined SE
      groups (Se and Se+MVT) had significantly lower risk of developing incident TB
      disease compared with placebo in multivariate adjusted models (hazard ratio=0.32,
      95% confidence interval: 0.11, 0.93, P=0.036). Multivitamins alone did not affect
      the incidence of TB. Isoniazid preventive therapy was received by 12.2% of
      participants, a rate that was not significantly different among the four study
      arms (P=0.122) and the newly diagnosed cases. Conclusion: Se supplementation,
      alone and with MVT, decreased the incidence of TB disease in PLWH who were ART
      naive. Supplementation with these micronutrients should be considered in HIV
      infection, prior to ART, in areas where TB and malnutrition are endemic.

PMID- 29187784
TI  - To be or not to be a subspecies: description of Saperda populnea lapponica ssp.
      n. (Coleoptera, Cerambycidae) developing in downy willow (Salix lapponum L.).
AB  - A new subspecies of the European cerambycid Saperda populnea (Linnaeus, 1758) is
      described: Saperda populnea lapponicassp. n. based on specimens from Scandinavia.
      The male genitalia characters were examined and found to provide support for this
      separation, as well as differences in morphology, geographical distribution and
      bionomy. The preferred host tree for the nominate subspecies S. populnea populnea
      is Populus tremula L., whereas S. populnea lapponicassp. n. is considered to be
      monophagous on Salix lapponum L. DNA sequence data of mitochondrial cytochrome
      oxidase subunit I (COI) was generated from Scandinavian specimens of S. populnea
      populnea and specimens representing S. populnea lapponicassp. n. The two
      subspecies were not reciprocally monophyletic and genetic distances in COI were
      small. All synonyms of S. populnea populnea have been considered, and species
      similar to S. populnea populnea have been examined, and not found to be related
      to S. populnea lapponicassp. n. A male lectotype has been designated for each of
      the two following synonyms: Cerambyx decempunctatus De Geer, 1775, and Saperda
      salicis Zetterstedt, 1818. The synonymised species from Asia, S. balsamifera
      (Motshulsky, 1860), is elevated to subspecies: S. populnea balsamiferastat. n. We
      end with a discussion on the definition of subspecies under the unified species
      concept.

PMID- 29187782
TI  - Death by a thousand cuts: The health implications of black respectability
      politics.
AB  - The authors introduce the concept of "vigilance," capturing behaviors that
      reflect attempts to navigate racialized social spaces on a daily basis.
      Specifically, vigilant behaviors include care about appearance and language to be
      treated with respect, avoidance of social spaces, and psychological preparation
      for potential prejudice and discrimination. Furthermore, these behaviors align
      with those discussed in Black respectability politics debates. Using data from a
      population-representative sample of Black adults in Chicago, they report that
      vigilance is associated with poor physical and mental health indexed through
      chronic health conditions, depressive symptoms, and self-rated health.

PMID- 29187785
TI  - Revision of Eucorydia Hebard, 1929 from China, with notes on the genus and
      species worldwide (Blattodea, Corydioidea, Corydiidae).
AB  - The cockroach genus Eucorydia from China is revised. Five new species are
      described and illustrated: Eucorydia linglongsp. n., Eucorydia pilosasp. n.,
      Eucorydia splendidasp. n., Eucorydia guilinensissp. n., and Eucorydia tangisp.
      n.. Corydia purpuralis Kirby, 1903 and Eucorydia paucipilosa Woo, Guo & Feng,
      1986 are confirmed to be junior synonyms of Eucorydia dasytoides (Walker, 1868).
      Eucorydia hilaris (Kirby, 1903) is newly recorded from China. This genus and
      currently known species from around the world are discussed. The status of
      Eucorydia maxwelli (Hanitsch, 1915) is revived. Corydia plagiata Walker, 1868 is
      confirmed to be a junior synonym of Eucorydia ornata (Saussure, 1864). A
      checklist, key, and photographs of members of this genus are provided.

PMID- 29187786
TI  - Three new cavernicolous species of the millipede genus Trichopeltis Pocock, 1894
      from southern China (Diplopoda, Polydesmida, Cryptodesmidae).
AB  - Three new species of Trichopeltis are described from caves in southern China: T.
      bellussp. n., T. intricatussp. n., and T. reflexussp. n., all presumed
      troglobites. The former two come from Yunnan Province, the latter one from Hunan
      Province. An updated key to all eleven currently known species of Trichopeltis is
      provided.

PMID- 29187787
TI  - Ancient diversity of Afrotropical Microborus: three endemic species - not one
      widespread.
AB  - The primarily Neotropical genus Microborus Blandford is represented with three
      species in Africa and Madagascar. The previously recorded species from this
      region, M. boops Blandford, is a Neotropical species restricted to Central
      America and is likely not found in the Afrotropics. The previously recognised
      species in western parts of Africa is M. camerunus (Eggers) and is resurrected
      from synonymy under M. boops. Molecular and morphological data revealed a second
      species of this complex in Madagascar, M. brevisetosus Jordal. Another new
      species, M. angustus Jordal, co-occurs with M. camerunus in Cameroon. Substantial
      genetic divergence indicate that Microborus was established in the Afrotropical
      region long before human transport across oceans. A key to Afrotropical species
      is provided.

PMID- 29187788
TI  - Scolytinae in hazelnut orchards of Turkey: clarification of species and
      identification key (Coleoptera, Curculionidae).
AB  - Hazelnut, a very important cash crop in Turkey, is frequently colonized by bark
      and ambrosia beetle species (Scolytinae). Some scolytine species may cause
      economic damage while other species do not; therefore, proper identification is
      important in orchard management. Extensive sampling demonstrated that the most
      common pest species in Turkey's hazelnut orchards are Anisandrus dispar,
      Xylosandrus germanus, and Xyleborinus saxesenii. Hypothenemus eruditus can also
      be common, but only colonizes branches that are already dead. Lymantor coryli,
      Hypoborus ficus, Taphrorychus ramicola, and Taphrorychus hirtellus are rare and
      do not causes damage to live plants. Xyleborinus saxesenii appears to have been
      frequently misidentified and misreported as either L. coryli or Xyleborus
      xylographus. The former is rare, and the latter probably does not occur in
      Turkey. To avoid future misidentifications, a dichotomous identification key is
      provided for bark and ambrosia beetles of hazelnut orchards in Turkey.

PMID- 29187789
TI  - Phylogenetic study of the genus Sternolophus Solier (Coleoptera, Hydrophilidae)
      based on adult morphology.
AB  - The phylogeny of the hydrophilid genus Sternolophus Solier, 1834 was examined in
      this study using 60 morphological adult characters, eight of them continuous and
      52 discrete. The cladistic analysis resulted in a single most parsimonious tree
      with two major subclades corresponding, respectively, to species previously
      assigned to the subgenera Sternolophus s. str. Solier and Neosternolophus
      Zaitzev, although they are not re-instated. The species groups S. angolensis
      (Erichson, 1843) and S. solieri Castelnau, 1840 are recovered as monophyletic.
      The biogeography and diversification of the species of Sternolophus are briefly
      discussed.

PMID- 29187790
TI  - Seahorses of the Hippocampus coronatus complex: taxonomic revision, and
      description of Hippocampus haema, a new species from Korea and Japan (Teleostei,
      Syngnathidae).
AB  - Morphological and molecular analyses were conducted on 182 specimens belonging to
      the Hippocampus coronatus complex (H. coronatus sensu lato), collected in Korea
      and Japan 1933-2015, in order to clarify the taxonomic status of the species
      within this complex. Three species are recognized based on the shape of the
      coronet, the number of trunk rings (TrR) and tail rings (TaR), and presence or
      absence of a wing-tip spine (WS) at the dorsal fin base. Hippocampus coronatus
      Temminck & Schlegel, 1850 (H. coronatus sensu stricto), is diagnosed by 10 TrR,
      37-40 TaR, an extremely high coronet (55.7-79.0 % head length) with four tips on
      the corona flat (CoT), and one WS. Hippocampus sindonis Jordan & Snyder, 1901 is
      diagnosed by 10 TrR, 35-38 TaR, a moderately high coronet (36.3-55.4 % HL) with
      five CoT, and no WS. A new species, H. haema is described on the basis of 140
      specimens, characterized by 10 TrR, 35-38 TaR, a moderately high coronet (34.1
      54.9 % head length) with four CoT, and two WS. Hippocampus haema is only known
      from the Korea Strait, western Kyushu, and East/Japan Sea. Recognition of the
      three species is supported by differences in mitochondrial DNA fragments
      (cytochrome b, 16S rRNA, and 12S rRNA).

PMID- 29187791
TI  - Earwigs from Brazilian caves, with notes on the taxonomic and nomenclatural
      problems of the Dermaptera (Insecta).
AB  - Based on samples collected during surveys of Brazilian cave fauna, seven earwig
      species are reported: Cylindrogaster cavernicola Kamimura, sp. n., Cylindrogaster
      sp. 1, Cylindrogaster sp. 2, Euborellia janeirensis, Euborellia brasiliensis,
      Paralabellula dorsalis, and Doru luteipes, as well as four species identified to
      the (sub)family level. To date, C. cavernicola Kamimura, sp. n. has been recorded
      only from cave habitats (but near entrances), whereas the other four organisms
      identified at the species level have also been recorded from non-cave habitats.
      Wings and female genital structures of Cylindrogaster spp. (Cylindrogastrinae)
      are examined for the first time. The genital traits, including the gonapophyses
      of the 8th abdominal segment shorter than those of the 9th segement, and venation
      of the hind wings of Cylindrogastrinae correspond to those of the members of
      Diplatyidae and not to Pygidicranidae. This is the first synopsis of cave
      dwelling earwigs of Brazil, one of the most species-rich areas of Dermaptera in
      the world.

PMID- 29187792
TI  - The real taxonomic identity of Trigona latitarsis Friese, 1900, with notes on
      type specimens (Hymenoptera, Apidae).
AB  - The taxonomic history of Trigona latitarsis Friese, 1900 and its clarification
      based on the observation of the types and literature data are treated in this
      study. The paper discusses the validity of the previously proposed lectotype,
      deposited in the ZMB (Berlin, Germany). Based on the type series deposited in
      HNHM (Budapest, Hungary) as well as the original description, a new lectotype and
      15 paralectotypes from Amazon forest (Sao Paulo de Olivenca, Amazonas) are
      designated. Data on the geographic distribution of Scaura latitarsis (Friese,
      1900) are provided.

PMID- 29187793
TI  - A new species of Phrynopus (Amphibia, Anura, Craugastoridae) from upper montane
      forests and high Andean grasslands of the Pui Pui Protected Forest in central
      Peru.
AB  - We describe a new species of Phrynopus from the upper montane forests and high
      Andean grasslands (puna) of the Pui Pui Protected Forest and its close
      surroundings (Region Junin, central Peru) and compare it morphologically and
      genetically with other species of Phrynopus. Phrynopus intisp. n. is known from
      four localities outside and two localities inside the Pui Pui Protected Forest
      between 3350 and 3890 m a.s.l. Studied specimens of the new species are
      characterized by a snout-vent length of 27.2-35.2 mm in males (n = 6), and 40.4
      mm in a single female, by having the skin on dorsum and flanks smooth with
      scattered tubercles, venter smooth, by lacking a tympanum, and males without
      vocal slits and nuptial pads. In life, the dorsum is pale grayish brown with or
      without dark brown blotches, or dorsum blackish brown with small yellow flecks,
      throat, chest and venter are pale grayish brown with salmon mottling, groin is
      pale grayish brown with salmon colored flecks, and the iris is golden orange with
      fine dark brown reticulations. The new species is morphologically most similar to
      Phrynopus kauneorum and P. juninensis. For the latter we describe the coloration
      in life for a specimen obtained at the type locality. A molecular phylogenetic
      analysis based on mitochondrial and nuclear DNA sequences inferred that the new
      species is most closely related to Phrynopus kauneorum, P. miroslawae, P.
      tautzorum, and an undescribed species distributed at high elevation in Region
      Pasco, central Peru.

PMID- 29187794
TI  - Reliability of CKD-EPI predictive equation in estimating chronic kidney disease
      prevalence in the Croatian endemic nephropathy area.
AB  - Introduction: Chronic kidney disease (CKD) is a significant public health problem
      and it is not possible to precisely predict its progression to terminal renal
      failure. According to current guidelines, CKD stages are classified based on the
      estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study
      were to determine the reliability of predictive equation in estimation of CKD
      prevalence in Croatian areas with endemic nephropathy (EN), compare the results
      with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was
      increased in subjects with EN. Materials and methods: A total of 1573 inhabitants
      of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages
      were enrolled. Participants were classified according to the modified criteria of
      the World Health Organization for EN. Estimated GFR was calculated using Chronic
      Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Results: The
      results showed a very high CKD prevalence in the Croatian rural area (19%). CKD
      prevalence was significantly higher in EN then in non EN villages with the lowest
      eGFR value in diseased subgroup. Conclusions: eGFR correlated significantly with
      the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation
      proved to be a good marker in differentiating the study subgroups, remained as
      one of the diagnostic criteria for EN.

PMID- 29187795
TI  - Fasting conditions: Influence of water intake on clinical chemistry analytes.
AB  - Introduction: Currently available recommendations regarding fasting requirements
      before phlebotomy do not specify any maximum water intake volume permitted during
      the fasting period. The aim was to study the effects of 300 mL water intake 1 h
      before phlebotomy on specific analytes. Materials and methods: Blood was
      collected from 20 women (median age (min-max): 24 (22 - 50) years) in basal state
      (T0) and 1 h after 300 mL water intake (T1). Glucose, total proteins (TP), urea,
      creatinine, cystatin C, total bilirubin (BT), total cholesterol, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (Tg),
      uric acid (UA), high-sensitivity C-reactive protein, gamma-glutamyl transferase
      (GGT), aspartate-aminotransferase (AST), alanine-aminotransferase and lactate
      dehydrogenase (LD) were studied. Results were analyzed using Wilcoxon test. Mean
      difference (%) was calculated for each analyte and was further compared with
      reference change value (RCV). Only mean differences (%) higher than RCV were
      considered clinically significant. Results: Significant differences (median T0vs
      median T1, P) were observed for TP (73 vs 74 g/L, 0.001); urea (4.08 vs 4.16
      mmol/L, 0.010); BT (12 vs 13 umol/L, 0.021); total cholesterol (4.9 vs 4.9
      mmol/L, 0.042); Tg (1.05 vs 1.06 mmol/L, 0.002); UA (260 vs 270 umol/L, 0.006);
      GGT (12 vs 12 U/L, 0.046); AST (22 vs 24 U/L, 0.001); and LD (364 vs 386 U/L,
      0.001). Although the differences observed were statistically significant, they
      were not indicative of clinically significant changes. Conclusions: A water
      intake of 300 mL 1 h prior to phlebotomy does not interfere with the analytes
      studied in the present work.

PMID- 29187796
TI  - Nurses' knowledge on phlebotomy in tertiary hospitals in China: a cross-sectional
      multicentric survey.
AB  - Introduction: In China, phlebotomy practice is mostly executed by nurses instead
      of phlebotomists. Our hypothesis was that these nurses may lack of knowledge on
      phlebotomy, especially factors influencing quality of blood samples. This study
      aims to assess the overall nurses' knowledge on phlebotomy to provide reference
      for improving blood sampling practice in China. Materials and methods: A survey
      was conducted involving nurses from 4 regions and 13 hospitals in China. A
      phlebotomy knowledge questionnaire was designed based on the Clinical and
      Laboratory Standards Institute H3-A6 guidelines, combining with the situations in
      China. Descriptive analysis and binary logistic regression analysis were used to
      analyze the knowledge level and its influencing factors. Results: A total of 3400
      questionnaires were distributed and 3077 valid questionnaires were returned, with
      an effective return rate of 90.5%. The correct rates of patient identification,
      hand sanitization, patient assessment, tube mixing time, needle disposing
      location and tube labelling were greater than 90%. However, the correct rates of
      order of draw (15.5%), definition of an inversion (22.5%), time to release
      tourniquet (18.5%) and time to change tube (28.5%) were relatively low. Binary
      logistic regression analysis showed that the correct rates of the aforementioned
      four questions were mainly related to the regional distribution of the hospitals
      (P < 0.001). Conclusions: The knowledge level on phlebotomy among Chinese nurses
      was found unsatisfactory in some areas. An education program on phlebotomy should
      be developed for Chinese nurses to improve the consistency among different
      regions and to enhance nurse's knowledge level on phlebotomy.

PMID- 29187797
TI  - Influence of centrifugation conditions on the results of 77 routine clinical
      chemistry analytes using standard vacuum blood collection tubes and the new BD
      Barricor tubes.
AB  - Introduction: Although centrifugation is performed in almost every blood sample,
      recommendations on duration and g-force are heterogeneous and mostly based on
      expert opinions. In order to unify this step in a fully automated laboratory, we
      aimed to evaluate different centrifugation settings and their influence on the
      results of routine clinical chemistry analytes. Materials and methods: We
      collected blood from 41 healthy volunteers into BD Vacutainer PST II-heparin-gel-
      (LiHepGel), BD Vacutainer SST II-serum-, and BD Vacutainer Barricor heparin-tubes
      with a mechanical separator (LiHepBar). Tubes were centrifuged at 2000xg for 10
      minutes and 3000xg for 7 and 5 minutes, respectively. Subsequently 60 and 21
      clinical chemistry analytes were measured in plasma and serum samples,
      respectively, using a Roche COBAS instrument. Results: High sensitive Troponin T,
      pregnancy-associated plasma protein A, beta human chorionic gonadotropin and
      rheumatoid factor had to be excluded from statistical evaluation as many of the
      respective results were below the measuring range. Except of free haemoglobin
      (fHb) measurements, no analyte result was altered by the use of shorter
      centrifugation times at higher g-forces. Comparing LiHepBar to LiHepGel tubes at
      different centrifugation setting, we found higher lactate-dehydrogenase (LD) (P =
      0.003 to < 0.001) and lower bicarbonate values (P = 0.049 to 0.008) in the
      latter. Conclusions: Serum and heparin samples may be centrifuged at higher speed
      (3000xg) for a shorter amount of time (5 minutes) without alteration of the
      analytes tested in this study. When using LiHepBar tubes for blood collection, a
      separate LD reference value might be needed.

PMID- 29187798
TI  - Missed detection of significant positive and negative shifts in gentamicin assay:
      implications for routine laboratory quality practices.
AB  - Introduction: A product recall was issued for the Roche/Hitachi Cobas Gentamicin
      II assays on 25th May 2016 in Australia, after a 15 - 20% positive analytical
      shift was discovered. Laboratories were advised to employ the Thermo Fisher
      Gentamicin assay as an alternative. Following the reintroduction of the revised
      assay on 12th September 2016, a second reagent recall was made on 20th March 2017
      after the discovery of a 20% negative analytical shift due to erroneous
      instrument adjustment factor. Materials and methods: The practices of an index
      laboratory were examined to determine how the analytical shifts evaded detection
      by routine internal quality control (IQC) and external quality assurance (EQA)
      systems. The ability of the patient result-based approaches, including moving
      average (MovAvg) and moving sum of outliers (MovSO) approaches in detecting these
      shifts were examined. Results: Internal quality control data of the index
      laboratory were acceptable prior to the product recall. The practice of adjusting
      IQC target following a change in assay method resulted in the missed negative
      shift when the revised Roche assay was reintroduced. While the EQA data of the
      Roche subgroup showed clear negative bias relative to other laboratory methods,
      the results were considered as possible 'matrix effect'. The MovAvg method
      detected the positive shift before the product recall. The MovSO did not detect
      the negative shift in the index laboratory but did so in another laboratory 5
      days before the second product recall. Conclusions: There are gaps in current
      laboratory quality practices that leave room for analytical errors to evade
      detection.

PMID- 29187799
TI  - Appropriateness of digoxin measurement in hospitalized patients.
AB  - Introduction: Measurement of serum digoxin concentrations before steady-state is
      reached results in a falsely low concentration, and may affect treatment safety.
      We evaluated the proportion of serum digoxin measurements performed before steady
      state is reached and the reasons for inappropriate sampling in hospitalized
      patients. Materials and methods: Electronic medical records of patients
      hospitalized between January 2011 and December 2015 treated with oral digoxin,
      that had more than one digoxin measurement were included. Serum digoxin
      measurements performed before achievement of pharmacological steady state were
      considered as inappropriate. The chi-square and chi-square for trend tests were
      used to analyse the relationship between inappropriate measurements and age,
      gender, diagnosis, inpatient service, serum digoxin, potassium and creatinine
      concentrations. Results: We evaluated 2065 hospital admissions for 1621 patients
      and 11,407 digoxin measurements. The time between consecutive measurements was
      1.9 +/- 2.4 days and 97% of all measurements were classified as inappropriate.
      There was no releationship between patient age, gender, serum creatinine
      concentration and inappropriate measurement. As opposed to expected,
      inappropriate digoxin measurement was higher when potassium concentrations were
      within the normal range (P = 0.025). Share of inappropriate determinations of
      digoxin was higher when concentrations > 2.6 nmol/L were recorded (P < 0.05).
      These measurements were requested most often in coronary care unit and cardiology
      department. Conclusions: In our study, inappropriate serum digoxin measurement
      was found to be very high although only one of the appropriateness criteria was
      evaluated. The findings reveal the need for some strategies to prevent
      inappropriate measurements and reduce costs.

PMID- 29187800
TI  - Reference intervals for six salivary cortisol measures based on the Croatian Late
      Adolescence Stress Study (CLASS).
AB  - Introduction: The aim of this nested study is to provide the reference intervals
      for already published measurements of salivary cortisol from the Croatian
      Adolescence Stress Study (CLASS). Material and methods: A total of 969
      individuals (372 males and 597 females) were included in the reference sample
      (age range: 18-21 years). Salivary cortisol concentrations were determined by the
      enzyme immunoassay (LUCIO-Medical ELISA Salivary Cortisol Kit, Nal von Minden,
      Germany) in the Department of Medical Laboratory Diagnostics, University Hospital
      Split. Nonparametric statistics were used for calculating the reference intervals
      (RIs) and 90% confidence intervals (90% CIs). Results: The lower limits of RIs
      determined by the direct method were higher in females (> 10%) than in males for
      the cortisol concentrations at awakening (SCC0), 30 to 45 after awakening (SCC30
      45) and at bedtime (SCCbedtime). The upper limits of RIs for the SCCbedtime were
      higher (> 10%) in males than in females. Females also had higher upper limits of
      RIs for the cortisol awakening response (CAR) and the diurnal cortisol slope
      (DCS) and higher lower limits of RIs for the CAR and the area under the curve
      with respect to ground (AUCG). The lower limits of RIs for the DCS were higher in
      males than in females. Conclusions: Obtained reference values open the arena for
      introducing salivary bioscience in Croatian clinical laboratory practice and
      provide important data for better understanding of gender differences in
      adaptation to stress during late adolescence.

PMID- 29187801
TI  - Upfront dilution of ferritin samples to reduce hook effect, improve turnaround
      time and reduce costs.
AB  - Introduction: Sandwich immunoassays offer advantages in the clinical laboratory
      but can yield erroneously low results due to hook (prozone) effect, especially
      with analytes whose concentrations span several orders of magnitude such as
      ferritin. This study investigated a new approach to reduce the likelihood of hook
      effect in ferritin immunoassays by performing upfront, five-fold dilutions of all
      samples for ferritin analysis. The impact of this change on turnaround time and
      costs were also investigated. Materials and methods: Ferritin concentrations were
      analysed in routine clinical practice with and without upfront dilutions on
      Siemens Centaur(r) XP (Siemens Healthineers, Erlang, Germany) immunoanalysers. In
      addition, one month of baseline data (1026 results) were collected prior to
      implementing upfront dilutions and one month of data (1033 results) were
      collected after implementation. Results: Without upfront dilutions, hook effect
      was observed in samples with ferritin concentrations as low as 86,028 ug/L. With
      upfront dilutions, samples with ferritin concentrations as high as 126,050 ug/L
      yielded values greater than the measurement interval and would have been diluted
      until an accurate value was obtained. The implementation of upfront dilution of
      ferritin samples led to a decrease in turnaround time from a median of 2 hours
      and 3 minutes to 1 hour and 18 minutes (P = 0.002). Conclusions: Implementation
      of upfront dilutions of all ferritin samples reduced the possibility of hook
      effect, improved turnaround time and saved the cost of performing additional
      dilutions.

PMID- 29187802
TI  - Radical distinction: Support for radical left and radical right parties in
      Europe.
AB  - Support for radical parties on both the left and right is on the rise, fueling
      intuition that both radicalisms have similar underpinnings. Indeed, existing
      studies show that radical left and right voters have overlapping positions and
      preferences. In this article, however, we focus on the differences in the voting
      bases of such parties. We show that radical left and right voters have sharply
      diverging ideological profiles. When it comes to the historical traditions of the
      'left' and 'right', these voters differ radically from each other. Both groups
      express the traditions associated with their mainstream counterparts-particularly
      with respect to (non-)egalitarian, (non-)altruistic, and (anti-)cosmopolitan
      values. Such differences also explain why radical left voters tend to be more,
      not less, educated than mainstream or radical right voters.

PMID- 29187803
TI  - The financial crisis and the European Parliament: An analysis of the Two-Pack
      legislation.
AB  - The left-right line of conflict has been the dominant dimension of decision
      making in the European Parliament since 1979. A pro-/anti-European Union
      integration dimension is of secondary importance. Limited evidence exists on the
      conditions under which these different dimensions matter. This study examines
      parliamentary decision-making about the so-called Two-Pack, which moved
      responsibilities about budgetary decision-making to the European Commission. The
      article uses in-depth interviews, textual analysis of committee debates and roll
      call voting analysis in order to determine which lines of conflict matter at
      which stage of decision-making. The evidence indicates that left-right division
      is dominant in the informal stage preceding committee debates, while both the pro
      /anti-European Union and the left/right dimensions matter during the committee
      stage, whereas for plenary votes, the pro-/anti-European Union dimension is
      crucial.

PMID- 29187804
TI  - Enforcement tool or strategic instrument? The initiation of ex-post legislative
      evaluations by the European Commission.
AB  - Whereas the European Commission officially intends to periodically evaluate all
      major European Union legislation in force, in practice it only evaluates a
      minority of major regulations and directives. This article tries to explain the
      variation in the initiation of such ex-post legislative evaluations by the
      Commission with the help of two theoretical motives: an enforcement motive and a
      strategic motive. Based on two novel datasets and binary logistic regression
      analysis, the results show that the type and complexity of the legislation, the
      presence of an evaluation clause and the evaluation capacity of the responsible
      Directorates-General enhance the chances of evaluation. These findings indicate
      that ex-post legislative evaluations are at least partly driven by the
      Commission's need to enforce legislation.

PMID- 29187805
TI  - How friends' involvement in crime affects the risk of offending and
      victimization.
AB  - This article examines how friends' involvement in crime influences such
      involvement in those around them, as offenders or victims, and the extent to
      which such friendship effects vary with contact frequency, friendship intimacy,
      and geographical proximity. To test our hypotheses we used four waves from the
      Dutch panel survey CrimeNL, which includes ego-centered network measures in each
      wave for respondents aged between 16 and 45. To test our hypotheses, fixed
      effects panel models were employed. The results show that living in close
      proximity to delinquent friends increases people's own risk of offending, and
      daily interaction with these friends decreases the risk of victimization.
      Victimization is also communicated among friends in their daily interactions.
      These findings stress the need to consider factors that condition how friendships
      exert influence on the risk of crime involvement.

PMID- 29187806
TI  - Absorption ratio of treatment couch and effect on surface and build-up region
      doses.
AB  - Aim: In this study, at different fields, energies and gantry angles, treatment
      couch and rails dose absorption ratio and treatment couch effect on surface and
      build-up region doses were examined. Background: It is assumed that radiation
      attenuation is minimal because the carbon fiber couches have low density and it
      is not generally accounted for during treatment planning. Consequently, it leads
      to a major dosimetric mistake. Materials and methods: Solid water phantom was
      used for relative dose measurement. The measurements were done using a Farmer ion
      chamber with 0.6 cc volume and a parallel plane ion chamber starting from surface
      with 1 mm depth intervals at 10 * 10 cm2 field, SSD 100 cm. Measurements were
      taken for situations where the beams intersect the couch and couch rails.
      Results: Dose absorption ratio of carbon fiber couch obtained at gantry angle of
      180 degrees  was 1.52%, 0.69%, 0.33% and 0.25% at different field sizes for 6 MV.
      For 15 MV, this ratio was 0.95%, 0.27%, 0.20% and 0.05%. The absorption ratio is
      between 3.4% and 1.22% when the beams intersect with couch rails. The couch
      effect increased surface dose from 14% to 70% for 6 MV and from 11.34% to 53.03%
      for 15 MV. Conclusions: The results showed that the carbon fiber couch increased
      surface dose during posterior irradiation. Therefore, the skin-sparing effect of
      the high energy beams was decreased. If the effect of couch is not considered, it
      may cause significant differences at dose which reaches the patient and may cause
      tissue problems such as erythema.

PMID- 29187807
TI  - Characteristic miRNA expression signature and random forest survival analysis
      identify potential cancer-driving miRNAs in a broad range of head and neck
      squamous cell carcinoma subtypes.
AB  - Aim: To characterize the miRNA expression profile in head and neck squamous cell
      carcinoma (HNSSC) accounting for a broad range of cancer subtypes and
      consequently identify an optimal miRNA signature with prognostic value.
      Background: HNSCC is consistently among the most common cancers worldwide. Its
      mortality rate is about 50% because of the characteristic aggressive behavior of
      these cancers and the prevalent late diagnosis. The heterogeneity of the disease
      has hampered the development of robust prognostic tools with broad clinical
      utility. Materials and methods: The Cancer Genome Atlas HNSC dataset was used to
      analyze level 3 miRNA-Seq data from 497 HNSCC patients. Differential expression
      (DE) analysis was implemented using the limma package and multivariate linear
      model that adjusted for the confounding effects of age at diagnosis, gender,
      race, alcohol history, anatomic neoplasm subdivision, pathologic stage, T and N
      stages, and vital status. Random forest (RF) for survival analysis was
      implemented using the randomForestSRC package. Results: A characteristic DE miRNA
      signature of HNSCC, comprised of 11 upregulated (i.e., miR-196b-5p, miR-1269a,
      miR-196a-5p, miR-4652-3p, miR-210-3p, miR-1293, miR-615-3p, miR-503-5p, miR-455
      3p, miR-205-5p, and miR-21-5p) and 9 downregulated (miR-376c-3p, miR-378c, miR
      29c-3p, miR-101-3p, miR-195-5p, miR-299-5p, miR-139-5p, miR-6510-3p, miR-375)
      miRNAs was identified. An optimal RF survival model was built from seven
      variables including age at diagnosis, miR-378c, miR-6510-3p, stage N, pathologic
      stage, gender, and race (listed in order of variable importance). Conclusions:
      The joint differential miRNA expression and survival analysis controlling for
      multiple confounding covariates implemented in this study allowed for the
      identification of a previously undetected prognostic miRNA signature
      characteristic of a broad range of HNSCC.

PMID- 29187808
TI  - Toward a Cognitive Neural Prosthesis Using Focused Ultrasound.
AB  - Non-invasive brain stimulation using focused ultrasound has many potential
      applications as a research and clinical tool, including its incorporation as
      either an extracorporeal or implantable neural prosthetic. To this end, we
      investigated the effect of focused ultrasound (FUS) combined with systemically
      administered microbubbles on visual-motor decision-making behavior in monkeys. We
      applied FUS to the putamen in one hemisphere to open the blood-brain barrier
      (BBB), and then tested behavioral performance 3-4 h later. On days when the
      monkeys were treated with FUS, their decisions were faster and more accurate than
      days without sonication. The performance improvement suggested both a shift in
      the decision criterion and an enhancement of the use of sensory evidence in the
      decision process. FUS also interacted with the effect of a low dose of
      haloperidol. The findings indicate that a two-minute application of FUS can have
      a sustained impact on performance of complex cognitive tasks, and may increase
      the efficacy of psychoactive medications. The results lend further support to the
      idea that the dorsal striatum plays an integral role in evidence- and reward
      based decision-making, and provide motivation for incorporating FUS into
      cognitive neural prosthetic devices.

PMID- 29187809
TI  - Spatiotemporal Beamforming: A Transparent and Unified Decoding Approach to
      Synchronous Visual Brain-Computer Interfacing.
AB  - Brain-Computer Interfaces (BCIs) decode brain activity with the aim to establish
      a direct communication channel with an external device. Albeit they have been
      hailed to (re-)establish communication in persons suffering from severe motor-
      and/or communication disabilities, only recently BCI applications have been
      challenging other assistive technologies. Owing to their considerably increased
      performance and the advent of affordable technological solutions, BCI technology
      is expected to trigger a paradigm shift not only in assistive technology but also
      in the way we will interface with technology. However, the flipside of the quest
      for accuracy and speed is most evident in EEG-based visual BCI where it has led
      to a gamut of increasingly complex classifiers, tailored to the needs of specific
      stimulation paradigms and use contexts. In this contribution, we argue that
      spatiotemporal beamforming can serve several synchronous visual BCI paradigms. We
      demonstrate this for three popular visual paradigms even without attempting to
      optimizing their electrode sets. For each selectable target, a spatiotemporal
      beamformer is applied to assess whether the corresponding signal-of-interest is
      present in the preprocessed multichannel EEG signals. The target with the highest
      beamformer output is then selected by the decoder (maximum selection). In
      addition to this simple selection rule, we also investigated whether interactions
      between beamformer outputs could be employed to increase accuracy by combining
      the outputs for all targets into a feature vector and applying three common
      classification algorithms. The results show that the accuracy of spatiotemporal
      beamforming with maximum selection is at par with that of the classification
      algorithms and interactions between beamformer outputs do not further improve
      that accuracy.

PMID- 29187811
TI  - Productive and Non-productive Pathways for Synaptotagmin 1 to Support Ca2+
      Triggered Fast Exocytosis.
AB  - Ca2+-triggered SNARE-mediated membrane fusion is essential for neuronal
      communication. The speed of this process is of particular importance because it
      sets a time limit to cognitive and physical activities. In this work, we expand
      the proteoliposome-to-supported bilayer (SBL) fusion assay by successfully
      incorporating synaptotagmin 1 (Syt1), a major Ca2+ sensor. We report that Syt1
      and Ca2+ together can elicit more than a 50-fold increase in the number of
      membrane fusion events when compared with membrane fusion mediated by SNAREs
      only. What is remarkable is that ~55% of all vesicle fusion events occurs within
      20 ms upon vesicle docking. Furthermore, pre-binding of Syt1 to SNAREs prior to
      Ca2+ inhibits spontaneous fusion, but intriguingly, this leads to a complete loss
      of the Ca2+ responsiveness. Thus, our results suggest that there is a productive
      and a non-productive pathway for Syt1, depending on whether there is a premature
      interaction between Syt1 and SNAREs. Our results show that Ca2+ binding to Syt1
      prior to Syt1's binding to SNAREs may be a prerequisite for the productive
      pathway. The successful reconstitution of Syt1 activities in the physiological
      time scale provides new opportunities to test the current mechanistic models for
      Ca2+-triggered exocytosis.

PMID- 29187810
TI  - Conditional Loss of Hoxa5 Function Early after Birth Impacts on Expression of
      Genes with Synaptic Function.
AB  - Hoxa5 is a member of the Hox gene family that plays critical roles in successive
      steps of the central nervous system formation during embryonic and fetal
      development. In the mouse, Hoxa5 was recently shown to be expressed in the
      medulla oblongata and the pons from fetal stages to adulthood. In these
      territories, Hoxa5 transcripts are enriched in many precerebellar neurons and
      several nuclei involved in autonomic functions, while the HOXA5 protein is
      detected mainly in glutamatergic and GABAergic neurons. However, whether HOXA5 is
      functionally required in these neurons after birth remains unknown. As a first
      approach to tackle this question, we aimed at determining the molecular programs
      downstream of the HOXA5 transcription factor in the context of the postnatal
      brainstem. A comparative transcriptomic analysis was performed in combination
      with gene expression localization, using a conditional postnatal Hoxa5 loss-of
      function mouse model. After inactivation of Hoxa5 at postnatal days (P)1-P4, we
      established the transcriptome of the brainstem from P21 Hoxa5 conditional mutants
      using RNA-Seq analysis. One major finding was the downregulation of several genes
      associated with synaptic function in Hoxa5 mutant specimens including different
      actors involved in glutamatergic synapse, calcium signaling pathway, and
      GABAergic synapse. Data were confirmed and extended by reverse transcription
      quantitative polymerase chain reaction analysis, and the expression of several
      HOXA5 candidate targets was shown to co-localize with Hoxa5 transcripts in
      precerebellar nuclei. Together, these new results revealed that HOXA5, through
      the regulation of key actors of the glutamatergic/GABAergic synapses and calcium
      signaling, might be involved in synaptogenesis, synaptic transmission, and
      synaptic plasticity of the cortico-ponto-cerebellar circuitry in the postnatal
      brainstem.

PMID- 29187812
TI  - Adrenomedullin Contributes to Age-Related Memory Loss in Mice and Is Elevated in
      Aging Human Brains.
AB  - Memory decline is common in elderly individuals and is the hallmark of
      Alzheimer's disease (AD). Memory failure follows the loss of synaptic contacts in
      the cerebral cortex and hippocampus, caused in part by cytoskeleton disruption.
      Adrenomedullin (AM) and its gene-related peptide, proadrenomedullin N-terminal 20
      peptide (PAMP), are microtubule-associated proteins (MAP) whose expression has
      been identified as a potential biomarker for predicting progression from
      predementia to clinical AD. Here we analyze the connection between AM levels and
      memory preservation. Mice lacking neuronal AM and PAMP (knockout, KO) and their
      wild type (WT) littermates were subjected, at different ages, to the novel object
      recognition test and the contextual fear conditioned test. Aged KO mice have
      significantly better retention memory than their WT counterparts. This feature
      was more prominent in females than in males. Prefrontal cortex and hippocampus
      samples from these animals were subjected to Western blotting for phospho-Tau and
      acetylated tubulin. Aged female KO mice had significantly less accumulation of
      phospho-Tau than their WT littermates. In addition, protein extracts from the
      frontal cortex of non-demented mature (65.10 +/- 3.86 years) and aged (77.14 +/-
      2.77 years) human donors were analyzed by Western blotting. Aged human brains had
      significantly higher levels of AM and lower levels of acetylated tubulin than
      younger donors. These observations suggest that drugs or interventions that
      reduce AM/PAMP expression may constitute a new avenue to prevent memory decline
      during normal aging and in patients suffering moderate AD in high risk of rapid
      cognitive decline.

PMID- 29187814
TI  - Olfaction and Pheromones: Uncanonical Sensory Influences and Bulbar Interactions.
AB  - The rodent main and accessory olfactory systems (AOS) are considered functionally
      and anatomically segregated information-processing pathways. Each system is
      devoted to the detection of volatile odorants and pheromones, respectively.
      However, a growing number of evidences supports a cooperative interaction between
      them. For instance, at least four non-canonical receptor families (i.e.,
      different from olfactory and vomeronasal receptor families) have been recently
      discovered. These atypical receptor families are expressed in the sensory organs
      of the nasal cavity and furnish parallel processing-pathways that detect specific
      stimuli and mediate specific behaviors as well. Aside from the receptor and
      functional diversity of these sensory modalities, they converge into a poorly
      understood bulbar area at the intersection of the main- main olfactory bulb (MOB)
      and accessory olfactory bulb (AOB) that has been termed olfactory limbus (OL).
      Given the intimate association the OL with specialized glomeruli (i.e., necklace
      and modified glomeruli) receiving uncanonical sensory afferences and its
      interactions with the MOB and AOB, the possibility that OL is a site of non
      olfactory and atypical vomeronasal sensory decoding is discussed.

PMID- 29187813
TI  - A miRNA Signature for Cognitive Deficits and Alcohol Use Disorder in Persons
      Living with HIV/AIDS.
AB  - HIV-associated neurocognitive disorders (HAND) affects more than half of persons
      living with HIV-1/AIDS (PLWHA). Identification of biomarkers representing the
      cognitive status of PLWHA is a critical step for implementation of successful
      cognitive, behavioral and pharmacological strategies to prevent onset and
      progression of HAND. However, the presence of co-morbidity factors in PLWHA, the
      most common being substance abuse, can prevent the identification of such
      biomarkers. We have optimized a protocol to profile plasma miRNAs using
      quantitative RT-qPCR and found a miRNA signature with very good discriminatory
      ability to distinguish PLWHA with cognitive impairment from those without
      cognitive impairment. Here, we have evaluated this miRNA signature in PLWHA with
      alcohol use disorder (AUD) at LSU Health Sciences Center (LSUHSC). The results
      show that AUD is a potential confounding factor for the miRNAs associated with
      cognitive impairment in PLWHA. Furthermore, we have investigated the miRNA
      signature associated with cognitive impairment in an independent cohort of PLWHA
      using plasma samples from the CNS HIV Antiretroviral Therapy Effects Research
      (CHARTER) program. Despite differences between the two cohorts in socioeconomic
      status, AUD, and likely misuse of illicit or prescription drugs, we validated a
      miRNA signature for cognitive deficits found at LSUHSC in the CHARTER samples.

PMID- 29187815
TI  - Comparative Performance of Linear Multielectrode Probes and Single-Tip Electrodes
      for Intracortical Microstimulation and Single-Neuron Recording in Macaque Monkey.
AB  - Intracortical microstimulation (ICMS) is one of the most widely employed
      techniques for providing causal evidence of the relationship between neuronal
      activity and specific motor, perceptual, or even cognitive functions. In recent
      years, several new types of linear multielectrode silicon probes have been
      developed, allowing researchers to sample neuronal activity at different depths
      along the same cortical site simultaneously and with high spatial precision.
      Nevertheless, silicon multielectrode probes have been rarely employed for ICMS
      studies and, more importantly, it is unknown whether and to what extent they can
      be used for combined recording and stimulation experiments. Here, we addressed
      these issues during both acute and chronic conditions. First, we compared the
      behavioral outcomes of ICMS delivered to the hand region of a monkey's motor
      cortex with multielectrode silicon probes, commercially available multisite
      stainless-steel probes and single-tip glass-coated tungsten microelectrodes. The
      results for all three of the probes were reliable and similar. Furthermore, we
      tested the impact of long-train ICMS delivered through chronically implanted
      silicon probes at different time intervals, from 1 to 198 days after ICMS
      sessions, showing that although the number of recorded neurons decreased over
      time, in line with previous studies, ICMS did not alter silicon probes' recording
      capabilities. These findings indicate that in ICMS experiments, the performance
      of linear multielectrode silicon probes is comparable to that of both single-tip
      and multielectrode stainless-steel probes, suggesting that the silicon probes can
      be successfully used for combined recording and stimulation studies in chronic
      conditions.

PMID- 29187816
TI  - Differential Effects of Oxytocin on Visual Perspective Taking for Men and Women.
AB  - Although oxytocin (OXT) has been shown to lead to reduced self-orientation, no
      study to date has directly and effectively weakened the egocentric tendencies in
      perspective taking tasks for both men and women. In this double-blind, placebo
      controlled, mixed design study we investigated the effects of OXT on men and
      women in visual perspective taking tasks. The results showed that OXT shortened
      the differences in response time between men and women in all experimental
      conditions. In addition, after OXT administration, the difference in reaction
      time between judging from one's own perspective and judging from others'
      perspectives decreased in female participants; however, this effect was not
      present in males. This may indicate that under OXT treatment, women have a higher
      tendency to overcome interference from their position and mindset when judging
      others' perspectives. However, OXT did not affect participants' accuracy, which
      is possibility because the used task was not suited to detect performance
      improvements caused by OXT. In summary, the above results may indicate that OXT
      could increase perspective-taking abilities through reducing self-bias and
      increasing the perception of others; furthermore, this trend mainly affected
      women rather than men.

PMID- 29187817
TI  - Predicting Long-Term Cognitive Outcome Following Breast Cancer with Pre-Treatment
      Resting State fMRI and Random Forest Machine Learning.
AB  - We aimed to determine if resting state functional magnetic resonance imaging
      (fMRI) acquired at pre-treatment baseline could accurately predict breast cancer
      related cognitive impairment at long-term follow-up. We evaluated 31 patients
      with breast cancer (age 34-65) prior to any treatment, post-chemotherapy and 1
      year later. Cognitive testing scores were normalized based on data obtained from
      43 healthy female controls and then used to categorize patients as impaired or
      not based on longitudinal changes. We measured clustering coefficient, a measure
      of local connectivity, by applying graph theory to baseline resting state fMRI
      and entered these metrics along with relevant patient-related and medical
      variables into random forest classification. Incidence of cognitive impairment at
      1 year follow-up was 55% and was predicted by classification algorithms with up
      to 100% accuracy (p < 0.0001). The neuroimaging-based model was significantly
      more accurate than a model involving patient-related and medical variables (p =
      0.005). Hub regions belonging to several distinct functional networks were the
      most important predictors of cognitive outcome. Characteristics of these hubs
      indicated potential spread of brain injury from default mode to other networks
      over time. These findings suggest that resting state fMRI is a promising tool for
      predicting future cognitive impairment associated with breast cancer. This
      information could inform treatment decision making by identifying patients at
      highest risk for long-term cognitive impairment.

PMID- 29187818
TI  - Executive Functions and Performance Variability Measured by Event-Related
      Potentials to Understand the Neural Bases of Perceptual Decision-Making.

PMID- 29187819
TI  - Binaural Beat: A Failure to Enhance EEG Power and Emotional Arousal.
AB  - When two pure tones of slightly different frequencies are delivered
      simultaneously to the two ears, is generated a beat whose frequency corresponds
      to the frequency difference between them. That beat is known as acoustic beat. If
      these two tones are presented one to each ear, they still produce the sensation
      of the same beat, although no physical combination of the tones occurs outside
      the auditory system. This phenomenon is called binaural beat. In the present
      study, we explored the potential contribution of binaural beats to the
      enhancement of specific electroencephalographic (EEG) bands, as previous studies
      suggest the potential usefulness of binaural beats as a brainwave entrainment
      tool. Additionally, we analyzed the effects of binaural-beat stimulation on two
      psychophysiological measures related to emotional arousal: heart rate and skin
      conductance. Beats of five different frequencies (4.53 Hz -theta-, 8.97 Hz -alpha
      , 17.93 Hz -beta-, 34.49 Hz -gamma- or 57.3 Hz -upper-gamma) were presented
      binaurally and acoustically for epochs of 3 min (Beat epochs), preceded and
      followed by pink noise epochs of 90 s (Baseline and Post epochs, respectively).
      In each of these epochs, we analyzed the EEG spectral power, as well as
      calculated the heart rate and skin conductance response (SCR). For all the beat
      frequencies used for stimulation, no significant changes between Baseline and
      Beat epochs were observed within the corresponding EEG bands, neither with
      binaural or with acoustic beats. Additional analysis of spectral EEG topographies
      yielded negative results for the effect of binaural beats in the scalp
      distribution of EEG spectral power. In the psychophysiological measures, no
      changes in heart rate and skin conductance were observed for any of the beat
      frequencies presented. Our results do not support binaural-beat stimulation as a
      potential tool for the enhancement of EEG oscillatory activity, nor to induce
      changes in emotional arousal.

PMID- 29187820
TI  - A Comprehensive Strategy to Evaluate Compatible Stability of Chinese Medicine
      Injection and Infusion Solutions Based on Chemical Analysis and Bioactivity
      Assay.
AB  - Stability of traditional Chinese medicine injection (TCMI) is an important issue
      related with its clinical application. TCMI is composed of multi-components,
      therefore, when evaluating TCMI stability, several marker compounds cannot
      represent global components or biological activities of TCMI. Till now, when
      evaluating TCMI stability, method involving the global components or biological
      activities has not been reported. In this paper, we established a comprehensive
      strategy composed of three different methods to evaluate the chemical and
      biological stability of a typical TCMI, Danhong injection (DHI). UHPLC-TQ/MS was
      used to analyze the stability of marker compounds (SaA, SaB, RA, DSS, PA, CA, and
      SG) in DHI, UHPLC-QTOF/MS was used to analyze the stability of global components
      (MW 80-1000 Da) in DHI, and cell based antioxidant capability assay was used to
      evaluate the bioactivity of DHI. We applied this strategy to assess the
      compatible stability of DHI and six infusion solutions (GS, NS, GNS, FI, XI, and
      DGI), which were commonly used in combination with DHI in clinic. GS was the best
      infusion solution for DHI, and DGI was the worst one based on marker compounds
      analysis. Based on global components analysis, XI and DGI were the worst infusion
      solutions for DHI. And based on bioactivity assay, GS was the best infusion
      solution for DHI, and XI was the worst one. In conclusion, as evaluated by the
      established comprehensive strategy, GS was the best infusion solution, however,
      XI and DGI were the worst infusion solutions for DHI. In the compatibility of DHI
      and XI or DGI, salvianolic acids in DHI would be degraded, resulting in the
      reduction of original composition and generation of new components, and leading
      to the changes of biological activities. This is the essence of instability
      compatibility of DHI and some infusion solutions. Our study provided references
      for choosing the reasonable infusion solutions for DHI, which could contribute
      the improvement of safety and efficacy of DHI. Moreover, the established strategy
      may be applied for the compatible stability evaluation of other TCMIs.

PMID- 29187821
TI  - Renoprotective Effect of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type
      2 Diabetes Mellitus.
AB  - Diabetic nephropathy is one of three major complications of diabetes mellitus,
      often leading to chronic renal failure requiring dialysis. Recently developed
      dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit renoprotective effects in
      addition to antihyperglycemic effects. In this study, we retrospectively
      investigated temporal changes in the renal function index of patients with type 2
      diabetes mellitus (DM) and examined the influence of DPP-4 inhibitors on renal
      function. Patients with type 2 DM (>18 years old) prescribed hypoglycemic agents
      at Gifu Municipal Hospital for >=3 months between March 2010 and April 2014 were
      included in the study. Renal function was evaluated as estimated the decline in
      12-month glomerular filtration rate from the baseline in patients receiving and
      not receiving DPP-4 inhibitors. Patient data from the DPP-4 inhibitor-treated
      (501 patients, 58.6%) and untreated (354, 41.4%) groups were analyzed using
      multiple logistic regression analysis, as well as Cox proportional-hazards
      regression analysis (616, 55.6% and 491, 44.4%, for DPP-4 inhibitors-treated and
      untreated groups). Multiple logistic regression analysis indicated that DPP-4
      inhibitors significantly lowered the estimated glomerular filtration rate (eGFR)
      decline [20% over 12 months; odds ratio (OR), 0.626; 95% confidence interval
      [CI], 0.409-0.958; P = 0.031]. Similar results were obtained using Cox
      proportional-hazards regression analysis (hazard ratio [HR], 0.707; 95% CI, 0.572
      0.874; P = 0.001). These findings suggest that DPP-4 inhibitors suppress the
      decrease of estimated glomerular filtration rate in patients with type 2 DM and
      show a renoprotective effect.

PMID- 29187822
TI  - Genomic Analysis of a Pathogenic Bacterium, Paeniclostridium sordellii CBA7122
      Containing the Highest Number of rRNA Operons, Isolated from a Human Stool
      Sample.

PMID- 29187823
TI  - Voluntary Exercise Improves Cardiac Function and Prevents Cardiac Remodeling in a
      Mouse Model of Dilated Cardiomyopathy.
AB  - Objective: Despite the indubitable beneficial effect of exercise to prevent of
      cardiovascular diseases, there is still a lack of studies investigating the
      impact of exercise in non-ischemic dilated cardiomyopathy. Here, we investigated
      the impact of voluntary exercise on cardiac function in a mouse model of non
      ischemic dilated cardiomyopathy (alphaMHC-MerCreMer:Sf/Sf), induced by cardiac
      specific inactivation of the Serum Response Factor. Materials and Methods: Seven
      days after tamoxifen injection, 20 alphaMHC-MerCreMer:Sf/Sf mice were assigned to
      sedentary (n = 8) and exercise (n = 12) groups. Seven additional alphaMHC
      MerCreMer:Sf/Sf mice without tamoxifen injection were used as control. The
      exercise group performed 4 weeks of voluntary running on wheel (1.8 +/- 0.12
      km/day). Cardiac function, myocardial fibrosis, and mitochondrial energetic
      pathways were then blindly assessed. Results: Exercised mice exhibited a smaller
      decrease of left ventricular (LV) fractional shortening and ejection fraction
      compared to control mice. This was associated with a lower degree of LV
      remodeling in exercised mice, as shown by a lower LV end-systolic
      intrerventricular septal and posterior wall thickness decrease from baseline
      values compared to sedentary mice. Moreover, exercised mice displayed a reduced
      gene expression of atrial and brain natriuretic factors. These benefits were
      associated by a reduced level of myocardial fibrosis. In addition, exercised mice
      exhibited a higher mitochondrial aconitase, voltage-dependent anion-selective
      channel 1 and PPAR gamma coactivators-1 alpha proteins levels suggesting that the
      increase of mitochondrial biogenesis and/or metabolism slowed the progression of
      dilated cardiomyopathy in exercised animals. Conclusions: In conclusion, our
      results support the role of voluntary exercise to improve outcomes in non
      ischemic dilated heart failure (HF) and also support its potential for a routine
      clinical use in the future.

PMID- 29187825
TI  - Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade
      in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats.
AB  - Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular
      endothelial function in spontaneous hypertensive rats (SHRs) and the underlying
      mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in
      myograph for force measurement. Expression and phosphorylation of endothelial
      nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by
      Western blotting. NO production was assayed by ELISA. Results: Rhy time- and
      concentration-dependently improved endothelium-dependent relaxation in the renal
      arteries from SHRs, but had no effect on endothelium-independent relaxation in
      SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or
      PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to
      acetylcholine by 12 h-incubation with 300 MUM Rhy. Western blot analysis revealed
      that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries.
      Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS
      induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the
      enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly,
      Rhy increased NO production and this effect was blocked by inhibition of Src or
      PI3K/Akt. Conclusion: The present study provides evidences for the first time
      that Rhy ameliorates endothelial dysfunction in SHRs through the activation of
      Src-PI3K/Akt-eNOS signaling pathway.

PMID- 29187824
TI  - The Implication of PGC-1alpha on Fatty Acid Transport across Plasma and
      Mitochondrial Membranes in the Insulin Sensitive Tissues.
AB  - PGC-1alpha coactivator plays a decisive role in the maintenance of lipid balance
      via engagement in numerous metabolic processes (i.e., Krebs cycle, beta
      oxidation, oxidative phosphorylation and electron transport chain). It
      constitutes a link between fatty acids import and their complete oxidation or
      conversion into bioactive fractions through the coordination of both the
      expression and subcellular relocation of the proteins involved in fatty acid
      transmembrane movement. Studies on cell lines and/or animal models highlighted
      the existence of an upregulation of the total and mitochondrial FAT/CD36, FABPpm
      and FATPs content in skeletal muscle in response to PGC-1alpha stimulation. On
      the other hand, the association between PGC-1alpha level or activity and the
      fatty acids transport in the heart and adipocytes is still elusive. So far, the
      effects of PGC-1alpha on the total and sarcolemmal expression of FAT/CD36, FATP1,
      and FABPpm in cardiomyocytes have been shown to vary in relation to the type of
      PPAR that was coactivated. In brown adipose tissue (BAT) PGC-1alpha knockdown was
      linked with a decreased level of lipid metabolizing enzymes and fatty acid
      transporters (FAT/CD36, FABP3), whereas the results obtained for white adipose
      tissue (WAT) remain contradictory. Furthermore, dysregulation in lipid turnover
      is often associated with insulin intolerance, which suggests the coactivator's
      potential role as a therapeutic target.

PMID- 29187827
TI  - The Long-Term Benefits of Positive Self-Presentation via Profile Pictures, Number
      of Friends and the Initiation of Relationships on Facebook for Adolescents' Self
      Esteem and the Initiation of Offline Relationships.
AB  - Social networking sites are a substantial part of adolescents' daily lives. By
      using a longitudinal approach the current study examined the impact of (a)
      positive self-presentation, (b) number of friends, and (c) the initiation of
      online relationships on Facebook on adolescents' self-esteem and their initiation
      of offline relationships, as well as the mediating role of positive feedback.
      Questionnaire data were obtained from 217 adolescents (68% girls, mean age 16.7
      years) in two waves. Adolescents' positive self-presentation and number of
      friends were found to be related to a higher frequency of receiving positive
      feedback, which in turn was negatively associated with self-esteem. However, the
      number of Facebook friends had a positive impact on self-esteem, and the
      initiation of online relationships positively influenced the initiation of
      offline relationships over time, demonstrating that Facebook may be a training
      ground for increasing adolescents' social skills. Implications and suggestions
      for future research are provided.

PMID- 29187826
TI  - Differences in the Thoracic Aorta by Region and Sex in a Murine Model of Marfan
      Syndrome.
AB  - Marfan syndrome (MFS) is a hereditary disorder of the connective tissue that
      causes life-threatening aortic aneurysm, which initiates at the aortic root and
      can progress into the ascending portion. However, analysis of ascending aorta
      reactivity in animal models of MFS has remained elusive. Epidemiologic evidence
      suggests that although MFS is equally prevalent in men and women, men are at a
      higher risk of aortic complications than non-pregnant women. Nevertheless, there
      is no experimental evidence to support this hypothesis. The aim of this study was
      to explore whether there are regional and sex differences in the thoracic aorta
      function of mice heterozygous for the fibrillin 1 (Fbn1) allele encoding a
      missense mutation (Fbn1C1039G/+), the most common class of mutation in MFS.
      Ascending and descending thoracic aorta reactivity was evaluated by wire
      myography. Ascending aorta mRNA and protein levels, and elastic fiber integrity
      were assessed by qRT-PCR, Western blotting, and Verhoeff-Van Gieson histological
      staining, respectively. MFS differently altered reactivity in the ascending and
      descending thoracic aorta by either increasing or decreasing phenylephrine
      contractions, respectively. When mice were separated by sex, contractions to
      phenylephrine increased progressively from 3 to 6 months of age in MFS ascending
      aortas of males, whereas contractions in females were unchanged. Endothelium
      dependent relaxation was unaltered in the MFS ascending aorta of either sex; an
      effect related to augmented endothelium-dependent hyperpolarization-type
      dilations. In MFS males, the non-selective cyclooxygenase (COX) inhibitor
      indomethacin prevented the MFS-induced enhancement of phenylephrine contractions
      linked to increased COX-2 expression. In MFS mice of both sexes, the non
      selective nitric oxide synthase inhibitor L-NAME revealed negative feedback of
      nitric oxide on phenylephrine contractions, which was associated with
      upregulation of eNOS in females. Finally, MFS ascending aortas showed a greater
      number of elastic fiber breaks than the wild-types, and males exhibited more
      breaks than females. These results show regional and sex differences in
      Fbn1C1039G/+ mice thoracic aorta contractility and aortic media injuries. The
      presence of more pronounced aortic alterations in male mice provides experimental
      evidence to support that male MFS patients are at increased risk of suffering
      aortic complications.

PMID- 29187828
TI  - On the Interpretation and Use of Mediation: Multiple Perspectives on Mediation
      Analysis.
AB  - Mediation analysis has become a very popular approach in psychology, and it is
      one that is associated with multiple perspectives that are often at odds, often
      implicitly. Explicitly discussing these perspectives and their motivations,
      advantages, and disadvantages can help to provide clarity to conversations and
      research regarding the use and refinement of mediation models. We discuss five
      such pairs of perspectives on mediation analysis, their associated advantages and
      disadvantages, and their implications: with vs. without a mediation hypothesis,
      specific effects vs. a global model, directness vs. indirectness of causation,
      effect size vs. null hypothesis testing, and hypothesized vs. alternative
      explanations. Discussion of the perspectives is facilitated by a small simulation
      study. Some philosophical and linguistic considerations are briefly discussed, as
      well as some other perspectives we do not develop here.

PMID- 29187829
TI  - Multisensory Motion Perception in 3-4 Month-Old Infants.
AB  - Human infants begin very early in life to take advantage of multisensory
      information by extracting the invariant amodal information that is conveyed
      redundantly by multiple senses. Here we addressed the question as to whether
      infants can bind multisensory moving stimuli, and whether this occurs even if the
      motion produced by the stimuli is only illusory. Three- to 4-month-old infants
      were presented with two bimodal pairings: visuo-tactile and audio-visual. Visuo
      tactile pairings consisted of apparently vertically moving bars (the Barber Pole
      illusion) moving in either the same or opposite direction with a concurrent
      tactile stimulus consisting of strokes given on the infant's back. Audio-visual
      pairings consisted of the Barber Pole illusion in its visual and auditory
      version, the latter giving the impression of a continuous rising or ascending
      pitch. We found that infants were able to discriminate congruently (same
      direction) vs. incongruently moving (opposite direction) pairs irrespective of
      modality (Experiment 1). Importantly, we also found that congruently moving visuo
      tactile and audio-visual stimuli were preferred over incongruently moving bimodal
      stimuli (Experiment 2). Our findings suggest that very young infants are able to
      extract motion as amodal component and use it to match stimuli that only
      apparently move in the same direction.

PMID- 29187830
TI  - The Role of Moral Suffering (Moral Distress and Moral Injury) in Police
      Compassion Fatigue and PTSD: An Unexplored Topic.

PMID- 29187832
TI  - Isolated Horizontal Gaze Palsy: Observations and Explanations.
AB  - We present three cases that we suggest require a novel diagnosis and a
      reconsideration of current understandings of pontine anatomy. In this case
      series, we highlight a series of patients with monophasic, fully recovering
      inflammatory lesions in the pontine tegmentum not due to any of the currently
      recognized causes of this syndrome. We highlight other similar cases in the
      literature and suggest there may be a particular epitope for an as-yet
      undiscovered antibody underlying the tropism for this area. We highlight the
      potential harm of misdiagnosis with relapsing inflammatory or other serious
      diagnoses with significant adverse impact on the patient. In addition, we propose
      that this would support a reinterpretation of the currently accepted anatomy of
      the pontine gaze inputs to the median longitudinal fasciculus and paramedian
      pontine reticular formation.

PMID- 29187831
TI  - Learning Where to Look for High Value Improves Decision Making Asymmetrically.
AB  - Decision making in any brain is imperfect and costly in terms of time and energy.
      Operating under such constraints, an organism could be in a position to improve
      performance if an opportunity arose to exploit informative patterns in the
      environment being searched. Such an improvement of performance could entail both
      faster and more accurate (i.e., reward-maximizing) decisions. The present study
      investigated the extent to which human participants could learn to take advantage
      of immediate patterns in the spatial arrangement of serially presented foods such
      that a region of space would consistently be associated with greater subjective
      value. Eye movements leading up to choices demonstrated rapidly induced biases in
      the selective allocation of visual fixation and attention that were accompanied
      by both faster and more accurate choices of desired goods as implicit learning
      occurred. However, for the control condition with its spatially balanced reward
      environment, these subjects exhibited preexisting lateralized biases for eye and
      hand movements (i.e., leftward and rightward, respectively) that could act in
      opposition not only to each other but also to the orienting biases elicited by
      the experimental manipulation, producing an asymmetry between the left and right
      hemifields with respect to performance. Potentially owing at least in part to
      learned cultural conventions (e.g., reading from left to right), the findings
      herein particularly revealed an intrinsic leftward bias underlying initial
      saccades in the midst of more immediate feedback-directed processes for which
      spatial biases can be learned flexibly to optimize oculomotor and manual control
      in value-based decision making. The present study thus replicates general
      findings of learned attentional biases in a novel context with inherently
      rewarding stimuli and goes on to further elucidate the interactions between
      endogenous and exogenous biases.

PMID- 29187833
TI  - Transcriptome Analysis on Single Small Yellow Follicles Reveals That Wnt4 Is
      Involved in Chicken Follicle Selection.
AB  - Ovarian follicle selection is an important process impacting the laying
      performance and fecundity of hens, and is regulated by follicle-stimulating
      hormone (FSH) through binding to its receptor [follicle-stimulating hormone
      receptor (FSHR)]. In laying hens, the small yellow follicle (6-8 mm in diameter)
      with the highest expression of FSHR will be recruited into the preovulatory
      hierarchy during ovarian follicle development. The study of molecular mechanism
      of chicken follicle selection is helpful for the identification of genes
      underlying egg-laying traits in chicken and other poultry species. Herein, the
      transcriptomes of chicken small yellow follicles differing in the mRNA expression
      of FSHR were compared, and a total of 17,993 genes were identified in 3 pairs of
      small yellow follicles. The Wnt signaling pathway was significantly enriched in
      the follicles with the greatest fold change in FSHR expression. In this pathway,
      the expression level of Wnt4 mRNA was significantly upregulated with a log2(fold
      change) of 2.12. We further investigated the expression, function, and regulation
      of Wnt4 during chicken follicle selection and found that Wnt4 mRNA reached its
      peak in small yellow follicles; Wnt4 stimulated the proliferation of follicular
      granulosa cells (GCs), increased the expression of StAR and CYP11A1 mRNA in
      prehierarchical and hierarchical follicles, increased the expression of FSHR
      mRNA, and decreased the expression of anti-Mullerian hormone and OCLN mRNA.
      Treatment with FSH significantly increased Wnt4 expression in GCs. Moreover, Wnt4
      facilitated the effects of FSH on the production of progesterone (P4) and the
      mRNA expression of steroidogenic enzyme genes in the GCs of hierarchical
      follicles, but inhibited the effects of FSH in the GCs of prehierarchical
      follicles. Collectively, these data suggest that Wnt4 plays an important role in
      chicken follicle selection by stimulating GC proliferation and steroidogenesis.
      This study provides a theoretical basis for improving the egg-laying performance
      of chicken and a reference for the elucidation of the molecular mechanism of
      follicular selection in mammals.

PMID- 29187835
TI  - Coastal Bacterioplankton Metabolism Is Stimulated Stronger by Anthropogenic
      Aerosols than Saharan Dust.
AB  - In oligotrophic regions, such as the Mediterranean Sea, atmospheric deposition
      has the potential to stimulate heterotrophic prokaryote growth and production in
      surface waters, especially during the summer stratification period. Previous
      studies focused on the role of leaching nutrients from mineral particles of
      Saharan (S) origin, and were restricted to single locations at given times of the
      year. In this study, we evaluate the effect of atmospheric particles from diverse
      sources and with a markedly different chemical composition [S dust and
      anthropogenic (A) aerosols] on marine planktonic communities from three locations
      of the northwestern Mediterranean with contrasted anthropogenic footprint.
      Experiments were also carried out at different times of the year, considering
      diverse initial conditions. We followed the dynamics of the heterotrophic
      community and a range of biogeochemical and physiological parameters in six
      experiments. While the effect of aerosols on bacterial abundance was overall low,
      bacterial heterotrophic production was up to 3.3 and 2.1 times higher in the
      samples amended with A and S aerosols, respectively, than in the controls.
      Extracellular enzymatic activities [leu-aminopeptidase (AMA) and beta-glucosidase
      (beta-Gl)] were also enhanced with aerosols, especially from A origin. AMA and
      beta-Gl increased up to 7.1 in the samples amended with A aerosols, and up to 1.7
      and 2.1 times, respectively, with S dust. The larger stimulation observed with A
      aerosols might be attributed to their higher content in nitrate. However, the
      response was variable depending the initial status of the seawater. In addition,
      we found that both A and S aerosols stimulated bacterial abundance and metabolism
      significantly more in the absence of competitors and predators.

PMID- 29187834
TI  - Characterization of Four Novel Bacteriophages Isolated from British Columbia for
      Control of Non-typhoidal Salmonella in Vitro and on Sprouting Alfalfa Seeds.
AB  - Alfalfa sprouts have been linked to numerous North American outbreaks of
      Salmonella in recent years. Conventionally, treatments involving chlorine, heat,
      and irradiation are used for alfalfa seed sanitation. However, such treatments
      may be highly variable in their efficacy for pathogen control and/or detrimental
      to sprout quality, therefore negatively perceived by consumers advocating for
      natural alternatives. The usage of bacteriophages for pathogen control in sprouts
      has been previously explored, although with conflicting and inconsistent results.
      Lytic phages, viral predators of bacteria, represent an attractive approach as
      they provide several advantages compared to conventional treatments, such as
      their high specificity for bacterial targets and their ubiquity in nature. In
      this study, four Salmonella phages were isolated from British Columbia, Canada
      and characterized with respect to host range, burst size, latent period, and
      environmental stability to assess their potential to control Salmonella. Phage
      isolate SI1 showed the greatest host range, highest burst size and shortest
      latent period, greatest stability across all pH and temperatures and was the most
      effective in control of S. Enteritidis in vitro. Therefore, SI1 was chosen for
      treatment of sprouting alfalfa seeds artificially contaminated with S.
      Enteritidis with a multiplicity of infection (MOI) of ~110 PFU/CFU. A significant
      (p < 0.05) reduction of 38.3 +/- 3.0% of viable Salmonella cells was observed
      following two h of phage treatment. On days two to six of the sprouting process,
      reductions of Salmonella were also observed, but were not significant compared to
      the control (p > 0.05). It was further demonstrated that the sprout yield was not
      significantly (p > 0.05) affected by phage treatment. These results highlight the
      potential of phages recovered from the British Columbia environment for use as
      biocontrol agents against Salmonella, although differing efficacies in vitro was
      observed. Moreover, the effectiveness of SI1 to significantly (p < 0.05) control
      Salmonella on sprouting alfalfa seeds on day 1 of treatment was demonstrated.
      Although promising, future work should aim to optimize this treatment to achieve
      more effective, and longer lasting, biocontrol of Salmonella in sprouting alfalfa
      seeds.

PMID- 29187836
TI  - Increased Adhesion of Listeria monocytogenes Strains to Abiotic Surfaces under
      Cold Stress.
AB  - Food contamination by Listeria monocytogenes remains a major concern for some
      food processing chains, particularly for ready-to-eat foods, including processed
      foods. Bacterial adhesion on both biotic and abiotic surfaces is a source of
      contamination by pathogens that have become more tolerant or even persistent in
      food processing environments, including in the presence of adverse conditions
      such as cold and dehydration. The most distinct challenge that bacteria confront
      upon entry into food processing environments is the sudden downshift in
      temperature, and the resulting phenotypic effects are of interest. Crystal violet
      staining and the BioFilm Ring Test(r) were applied to assess the adhesion and
      biofilm formation of 22 listerial strains from different serogroups and origins
      under cold-stressed and cold-adapted conditions. The physicochemical properties
      of the bacterial surface were studied using the microbial adhesion to solvent
      technique. Scanning electron microscopy was performed to visualize cell
      morphology and biofilm structure. The results showed that adhesion to stainless
      steel and polystyrene was increased by cold stress, whereas cold-adapted cells
      remained primarily in planktonic form. Bacterial cell surfaces exhibited electron
      donating properties regardless of incubation temperature and became more
      hydrophilic as temperature decreased from 37 to 4 degrees C. Moreover, the
      adhesion of cells grown at 4 degrees C correlated with affinity for ethyl
      acetate, indicating the role of cell surface properties in adhesion.

PMID- 29187837
TI  - Microbiome Datasets Are Compositional: And This Is Not Optional.
AB  - Datasets collected by high-throughput sequencing (HTS) of 16S rRNA gene
      amplimers, metagenomes or metatranscriptomes are commonplace and being used to
      study human disease states, ecological differences between sites, and the built
      environment. There is increasing awareness that microbiome datasets generated by
      HTS are compositional because they have an arbitrary total imposed by the
      instrument. However, many investigators are either unaware of this or assume
      specific properties of the compositional data. The purpose of this review is to
      alert investigators to the dangers inherent in ignoring the compositional nature
      of the data, and point out that HTS datasets derived from microbiome studies can
      and should be treated as compositions at all stages of analysis. We briefly
      introduce compositional data, illustrate the pathologies that occur when
      compositional data are analyzed inappropriately, and finally give guidance and
      point to resources and examples for the analysis of microbiome datasets using
      compositional data analysis.

PMID- 29187838
TI  - Rv2629 Overexpression Delays Mycobacterium smegmatis and Mycobacteria
      tuberculosis Entry into Log-Phase and Increases Pathogenicity of Mycobacterium
      smegmatis in Mice.
AB  - Objective: The aim of the present study was to explore the potential biological
      role of Rv2629 in Mycobacterium smegmatis and Mycobacterium tuberculosis.Methods:
      Recombinant wild type and mutant Rv2629 strains were constructed. Rv2629
      expression was evaluated by real-time PCR and western blot. Microarray and
      interaction network analyses were used to identify the gene interactions
      associated with wild type and mutant Rv2629. Bacterial growth was assessed in
      Balb/c mice infected with wild type and mutant Rv2629 strains using CFU assay and
      histological analysis of the organs. Results: Overexpression of Rv2629 could
      delay the entry of the Mycobacterium tuberculosis cells into the log-phase, while
      Rv2629 decreased the number of ribosomes and the expression of uridylate kinase
      in Mycobacterium smegmatis. The Gene Ontology (GO) and pathway analysis indicated
      that 122 genes correlated with wild type Rv2629, whereas the Rv2629 mutation led
      to decrease in the ribosome production, oxidative phosphorylation, and virulence
      in Mycobacterium tuberculosis. Overexpression of Rv2629 slightly enhanced the
      drug resistance of Mycobacterium smegmatis to antibiotics, and increased its
      survival and pathogenicity in Balb/c mice. Conclusion: It is suggested that
      Rv2629 is involved in the survival of the clinical drug-resistant strain via
      bacterial growth repression and bacterial persistence induction.

PMID- 29187839
TI  - The Glutaminase-Dependent System Confers Extreme Acid Resistance to New Species
      and Atypical Strains of Brucella.
AB  - Neutralophilic bacteria have developed specific mechanisms to cope with the acid
      stress encountered in environments such as soil, fermented foods, and host
      compartments. In Escherichia coli, the glutamate decarboxylase (Gad)-dependent
      system is extremely efficient: it requires the concerted action of glutamate
      decarboxylase (GadA/GadB) and of the glutamate (Glu)/gamma-aminobutyrate
      antiporter, GadC. Notably, this system is operative also in new strains/species
      of Brucella, among which Brucella microti, but not in the "classical" species,
      with the exception of marine mammals strains. Recently, the glutaminase-dependent
      system (named AR2_Q), relying on the deamination of glutamine (Gln) into Glu and
      on GadC activity, was described in E. coli. In Brucella genomes, a putative
      glutaminase (glsA)-coding gene is located downstream of the gadBC genes. We found
      that in B. microti these genes are expressed as a polycistronic transcript.
      Moreover, using a panel of Brucella genus-representative strains, we show that
      the AR2_Q system protects from extreme acid stress (pH <=2.5), in the sole
      presence of Gln, only the Brucella species/strains predicted to have functional
      glsA and gadC. Indeed, mutagenesis approaches confirmed the involvement of glsA
      and gadC of B. microti in AR2_Q and that the acid-sensitive phenotype of B.
      abortus can be ascribed to a Ser248Leu substitution in GlsA, leading to loss of
      glutaminase activity. Furthermore, we found that the gene BMI_II339, of unknown
      function and downstream of the gadBC-glsA operon, positively affects Gad- and
      GlsA-dependent AR. Thus, we identified novel determinants that allow newly
      discovered and marine mammals Brucella strains to be better adapted to face
      hostile acidic environments. As for significance, this work may contribute to the
      understanding of the host preferences of Brucella species and opens the way to
      alternative diagnostic targets in epidemiological surveillance of brucellosis.

PMID- 29187840
TI  - Prion-Like Domains in Phagobiota.
AB  - Prions are molecules characterized by self-propagation, which can undergo a
      conformational switch leading to the creation of new prions. Prion proteins have
      originally been associated with the development of mammalian pathologies;
      however, recently they have been shown to contribute to the environmental
      adaptation in a variety of prokaryotic and eukaryotic organisms. Bacteriophages
      are widespread and represent the important regulators of microbiota homeostasis
      and have been shown to be diverse across various bacterial families. Here, we
      examined whether bacteriophages contain prion-like proteins and whether these
      prion-like protein domains are involved in the regulation of homeostasis. We used
      a computational algorithm, prion-like amino acid composition, to detect prion
      like domains in 370,617 publicly available bacteriophage protein sequences, which
      resulted in the identification of 5040 putative prions. We analyzed a set of
      these prion-like proteins, and observed regularities in their distribution across
      different phage families, associated with their interactions with the bacterial
      host cells. We found that prion-like domains could be found across all phages of
      various groups of bacteria and archaea. The results obtained in this study
      indicate that bacteriophage prion-like proteins are predominantly involved in the
      interactions between bacteriophages and bacterial cell, such as those associated
      with the attachment and penetration of bacteriophage in the cell, and the release
      of the phage progeny. These data allow the identification of phage prion-like
      proteins as novel regulators of the interactions between bacteriophages and
      bacterial cells.

PMID- 29187841
TI  - Genome Comparison of Erythromycin Resistant Campylobacter from Turkeys Identifies
      Hosts and Pathways for Horizontal Spread of erm(B) Genes.
AB  - Pathogens in the genus Campylobacter are the most common cause of food-borne
      bacterial gastro-enteritis. Campylobacteriosis, caused principally by
      Campylobacter jejuni and Campylobacter coli, is transmitted to humans by food of
      animal origin, especially poultry. As for many pathogens, antimicrobial
      resistance in Campylobacter is increasing at an alarming rate. Erythromycin
      prescription is the treatment of choice for clinical cases requiring
      antimicrobial therapy but this is compromised by mobility of the erythromycin
      resistance gene erm(B) between strains. Here, we evaluate resistance to six
      antimicrobials in 170 Campylobacter isolates (133 C. coli and 37 C. jejuni) from
      turkeys. Erythromycin resistant isolates (n = 85; 81 C. coli and 4 C. jejuni)
      were screened for the presence of the erm(B) gene, that has not previously been
      identified in isolates from turkeys. The genomes of two positive C. coli isolates
      were sequenced and in both isolates the erm(B) gene clustered with resistance
      determinants against aminoglycosides plus tetracycline, including aad9, aadE,
      aph(2")-IIIa, aph(3')-IIIa, and tet(O) genes. Comparative genomic analysis
      identified identical erm(B) sequences among Campylobacter from turkeys,
      Streptococcus suis from pigs and Enterococcus faecium and Clostridium difficile
      from humans. This is consistent with multiple horizontal transfer events among
      different bacterial species colonizing turkeys. This example highlights the
      potential for dissemination of antimicrobial resistance across bacterial species
      boundaries which may compromise their effectiveness in antimicrobial therapy.

PMID- 29187842
TI  - Low Microbial Diversity and Abnormal Microbial Succession Is Associated with
      Necrotizing Enterocolitis in Preterm Infants.
AB  - Despite increased efforts, the diverse etiologies of Necrotizing Enterocolitis
      (NEC) have remained largely elusive. Clinical predictors of NEC remain ill
      defined and currently lack sufficient specificity. The development of a thorough
      understanding of initial gut microbiota colonization pattern in preterm infants
      might help to improve early detection or prediction of NEC and its associated
      morbidities. Here we compared the fecal microbiota successions, microbial
      diversity, abundance and structure of newborns that developed NEC with preterm
      controls. A 16S rRNA based microbiota analysis was conducted in a total of 132
      fecal samples that included the first stool (meconium) up until the 5th week of
      life or NEC diagnosis from 40 preterm babies (29 controls and 11 NEC cases). A
      single phylotype matching closest to the Enterobacteriaceae family correlated
      strongly with NEC. In DNA from the sample with the greatest abundance of this
      phylotype additional shotgun metagenomic sequencing revealed Citrobacter koseri
      and Klebsiella pneumoniae as the dominating taxa. These two taxa might represent
      suitable microbial biomarker targets for early diagnosis of NEC. In NEC cases, we
      further detected lower microbial diversity and an abnormal succession of the
      microbial community before NEC diagnosis. Finally, we also detected a disruption
      in anaerobic microorganisms in the co-occurrence network of meconium samples from
      NEC cases. Our data suggest that a strong dominance of Citrobacter koseri and/or
      Klebsiella pneumoniae, low diversity, low abundance of Lactobacillus, as well as
      an altered microbial-network structure during the first days of life, correlate
      with NEC risk in preterm infants. Confirmation of these findings in other
      hospitals might facilitate the development of a microbiota based screening
      approach for early detection of NEC.

PMID- 29187843
TI  - Profiling of Oral Microbiota in Early Childhood Caries Using Single-Molecule Real
      Time Sequencing.
AB  - Background: Alterations of oral microbiota are the main cause of the progression
      of caries. The goal of this study was to characterize the oral microbiota in
      childhood caries based on single-molecule real-time sequencing. Methods: A total
      of 21 preschoolers, aged 3-5 years old with severe early childhood caries, and 20
      age-matched, caries-free children as controls were recruited. Saliva samples were
      collected, followed by DNA extraction, Pacbio sequencing, and phylogenetic
      analyses of the oral microbial communities. Results: Eight hundred and seventy
      six species derived from 13 known bacterial phyla and 110 genera were detected
      from 41 children using Pacbio sequencing. At the species level, 38 species,
      including Veillonella spp., Streptococcus spp., Prevotella spp., and
      Lactobacillus spp., showed higher abundance in the caries group compared to the
      caries-free group (p < 0.05). The core microbiota at the genus and species levels
      was more stable in the caries-free micro-ecological niche. At follow-up, oral
      examinations 6 months after sample collection, development of new dental caries
      was observed in 5 children (the transitional group) among the 21 caries free
      children. Compared with the caries-free children, in the transitional and caries
      groups, 6 species, which were more abundant in the caries-free group, exhibited a
      relatively low abundance in both the caries group and the transitional group (p <
      0.05). We conclude that Abiotrophia spp., Neisseria spp., and Veillonella spp.,
      might be associated with healthy oral microbial ecosystem. Prevotella spp.,
      Lactobacillus spp., Dialister spp., and Filifactor spp. may be related to the
      pathogenesis and progression of dental caries.

PMID- 29187844
TI  - speG Is Required for Intracellular Replication of Salmonella in Various Human
      Cells and Affects Its Polyamine Metabolism and Global Transcriptomes.
AB  - The speG gene has been reported to regulate polyamine metabolism in Escherichia
      coli and Shigella, but its role in Salmonella remains unknown. Our preliminary
      studies have revealed that speG widely affects the transcriptomes of infected in
      vitro M and Caco-2 cells and that it is required for the intracellular
      replication of Salmonella enterica serovar Typhimurium (S. Typhimurium) in HeLa
      cells. In this study, we demonstrated that speG plays a time-dependent and cell
      type-independent role in the intracellular replication of S. Typhimurium.
      Moreover, high-performance liquid chromatography (HPLC) of four major polyamines
      demonstrated putrescine, spermine, and cadaverine as the leading polyamines in S.
      Typhimurium. The deletion of speG significantly increased the levels of the three
      polyamines in intracellular S. Typhimurium, suggesting the inhibitory effect of
      speG on the biosynthesis of these polyamines. The deletion of speG was associated
      with elevated levels of these polyamines in the attenuated intracellular
      replication of S. Typhimurium in host cells. This result was subsequently
      validated by the dose-dependent suppression of intracellular proliferation after
      the addition of the polyamines. Furthermore, our RNA transcriptome analysis of S.
      Typhimurium SL1344 and its speG mutant outside and inside Caco-2 cells revealed
      that speG regulates the genes associated with flagellar biosynthesis, fimbrial
      expression, and functions of types III and I secretion systems. speG also affects
      the expression of genes that have been rarely reported to correlate with
      polyamine metabolism in Salmonella, including those associated with the
      periplasmic nitrate reductase system, glucarate metabolism, the
      phosphotransferase system, cytochromes, and the succinate reductase complex in S.
      Typhimurium in the mid-log growth phase, as well as those in the ilv-leu and
      histidine biosynthesis operons of intracellular S. Typhimurium after invasion in
      Caco-2 cells. In the present study, we characterized the phenotypes and
      transcriptome effects of speG in S. Typhimurium and reviewed the relevant
      literature to facilitate a more comprehensive understanding of the potential role
      of speG in the polyamine metabolism and virulence regulation of Salmonella.

PMID- 29187845
TI  - Loss of Genome Fidelity: Beta HPVs and the DNA Damage Response.
AB  - While the role of genus alpha human papillomaviruses in the tumorigenesis and
      tumor maintenance of anogenital and oropharyngeal cancers is well-established,
      the role of genus beta human papilloviruses (beta-HPVs) in non-melanoma skin
      cancers (NMSCs) is less certain. Persistent beta-HPV infections cause NMSCs in
      sun-exposed skin of people with a rare genetic disorder, epidermodysplasia
      verruciformis. However, beta-HPV infections in people without epidermodysplasia
      verruciformis are typically transient. Further, beta-HPV gene expression is not
      necessary for tumor maintenance in the general population as on average there is
      fewer than one copy of the beta-HPV genome per cell in NMSC tumor biopsies. Cell
      culture, epidemiological, and mouse model experiments support a role for beta-HPV
      infections in the initiation of NMSCs through a "hit and run" mechanism. The
      virus is hypothesized to act as a cofactor, augmenting the genome destabilizing
      effects of UV. Supporting this idea, two beta-HPV proteins (beta-HPV E6 and E7)
      disrupt the cellular response to UV exposure and other genome destabilizing
      events by abrogating DNA repair and deregulating cell cycle progression. The
      aberrant damage response increases the likelihood of oncogenic mutations capable
      of driving tumorigenesis independent of a sustained beta-HPV infection or
      continued viral protein expression. This review summarizes what is currently
      known about the deleterious effects of beta-HPV on genome maintenance in the
      context of the virus's putative role in NMSC initiation.

PMID- 29187847
TI  - A Multilayered Control of the Human Survival Motor Neuron Gene Expression by Alu
      Elements.
AB  - Humans carry two nearly identical copies of Survival Motor Neuron gene: SMN1 and
      SMN2. Mutations or deletions of SMN1, which codes for SMN, cause spinal muscular
      atrophy (SMA), a leading genetic disease associated with infant mortality.
      Aberrant expression or localization of SMN has been also implicated in other
      pathological conditions, including male infertility, inclusion body myositis,
      amyotrophic lateral sclerosis and osteoarthritis. SMN2 fails to compensate for
      the loss of SMN1 due to skipping of exon 7, leading to the production of
      SMNDelta7, an unstable protein. In addition, SMNDelta7 is less functional due to
      the lack of a critical C-terminus of the full-length SMN, a multifunctional
      protein. Alu elements are specific to primates and are generally found within
      protein coding genes. About 41% of the human SMN gene including promoter region
      is occupied by more than 60 Alu-like sequences. Here we discuss how such an
      abundance of Alu-like sequences may contribute toward SMA pathogenesis. We
      describe the likely impact of Alu elements on expression of SMN. We have recently
      identified a novel exon 6B, created by exonization of an Alu-element located
      within SMN intron 6. Irrespective of the exon 7 inclusion or skipping,
      transcripts harboring exon 6B code for the same SMN6B protein that has altered C
      terminus compared to the full-length SMN. We have demonstrated that SMN6B is more
      stable than SMNDelta7 and likely functions similarly to the full-length SMN. We
      discuss the possible mechanism(s) of regulation of SMN exon 6B splicing and
      potential consequences of the generation of exon 6B-containing transcripts.

PMID- 29187846
TI  - To Be or Not To Be T4: Evidence of a Complex Evolutionary Pathway of Head
      Structure and Assembly in Giant Salmonella Virus SPN3US.
AB  - Giant Salmonella phage SPN3US has a 240-kb dsDNA genome and a large complex
      virion composed of many proteins for which the functions of most are undefined.
      We recently determined that SPN3US shares a core set of genes with related giant
      phages and sequenced and characterized 18 amber mutants to facilitate its use as
      a genetic model system. Notably, SPN3US and related giant phages contain a bolus
      of ejection proteins within their heads, including a multi-subunit virion RNA
      polymerase (vRNAP), that enter the host cell with the DNA during infection. In
      this study, we characterized the SPN3US virion using mass spectrometry to gain
      insight into its head composition and the features that its head shares with
      those of related giant phages and with T4 phage. SPN3US has only homologs to the
      T4 proteins critical for prohead shell formation, the portal and major capsid
      proteins, as well as to the major enzymes essential for head maturation, the
      prohead protease and large terminase subunit. Eight of ~50 SPN3US head proteins
      were found to undergo proteolytic processing at a cleavage motif by the prohead
      protease gp245. Gp245 undergoes auto-cleavage of its C-terminus, suggesting this
      is a conserved activation and/or maturation feature of related phage proteases.
      Analyses of essential head gene mutants showed that the five subunits of the
      vRNAP must be assembled for any subunit to be incorporated into the prohead,
      although the assembled vRNAP must then undergo subsequent major conformational
      rearrangements in the DNA packed capsid to allow ejection through the ~30 A
      diameter tail tube for transcription from the injected DNA. In addition, ejection
      protein candidate gp243 was found to play a critical role in head assembly. Our
      analyses of the vRNAP and gp243 mutants highlighted an unexpected dichotomy in
      giant phage head maturation: while all analyzed giant phages have a homologous
      protease that processes major capsid and portal proteins, processing of ejection
      proteins is not always a stable/defining feature. Our identification in SPN3US,
      and related phages, of a diverged paralog to the prohead protease further hints
      toward a complicated evolutionary pathway for giant phage head structure and
      assembly.

PMID- 29187848
TI  - Kaempferol Inhibits the Primary Attachment Phase of Biofilm Formation in
      Staphylococcus aureus.
AB  - The ability to form biofilms on surfaces makes Staphylococcus aureus the main
      pathogenic factor in implanted medical device infections. The aim of this study
      was to discover a biofilm inhibitor distinct from the antibiotics used to prevent
      infections resulting from S. aureus biofilms. Here, we describe kaempferol, a
      small molecule with anti-biofilm activity that specifically inhibited the
      formation of S. aureus biofilms. Crystal violet (CV) staining and fluorescence
      microscopy clearly showed that 64 MUg/ml kaempferol inhibited biofilm formation
      by 80%. Meanwhile, the minimum inhibitory concentration (MIC) and growth curve
      results indicated that kaempferol had no antibacterial activity against the
      tested bacterial strain. Kaempferol inhibited the primary attachment phase of
      biofilm formation, as determined by a fibrinogen-binding assay. Moreover, a
      fluorescence resonance energy transfer (FRET) assay and quantitative real-time
      reverse transcription polymerase chain reaction (qRT-PCR) analyses revealed that
      kaempferol reduced the activity of S. aureus sortaseA (SrtA) and the expression
      of adhesion-related genes. Based on these results, kaempferol provides a starting
      point for the development of novel anti-biofilm drugs, which may decrease the
      risk of bacterial drug resistance, to prevent S. aureus biofilm-related
      infections.

PMID- 29187849
TI  - Quantification of Inter-Sample Differences in T-Cell Receptor Repertoires Using
      Sequence-Based Information.
AB  - Inter-sample comparisons of T-cell receptor (TCR) repertoires are crucial for
      gaining a better understanding of the immunological states determined by
      different collections of T cells from different donor sites, cell types, and
      genetic and pathological backgrounds. For quantitative comparison, most previous
      studies utilized conventional methods in ecology, which focus on TCR sequences
      that overlap between pairwise samples. Some recent studies attempted another
      approach that is categorized into Poisson abundance models using the abundance
      distribution of observed TCR sequences. However, these methods ignore the details
      of the measured sequences and are consequently unable to identify sub-repertoires
      that might have important contributions to the observed inter-sample differences.
      Moreover, the sparsity of sequence data due to the huge diversity of repertoires
      hampers the performance of these methods, especially when few overlapping
      sequences exist. In this paper, we propose a new approach for REpertoire
      COmparison in Low Dimensions (RECOLD) based on TCR sequence information, which
      can estimate the low-dimensional structure by embedding the pairwise sequence
      dissimilarities in high-dimensional sequence space. The inter-sample differences
      between repertoires are then quantified by information-theoretic measures among
      the distributions of data estimated in the embedded space. Using datasets of
      mouse and human TCR repertoires, we demonstrate that RECOLD can accurately
      identify the inter-sample hierarchical structures, which have a good
      correspondence with our intuitive understanding about sample conditions.
      Moreover, for the dataset of transgenic mice that have strong restrictions on the
      diversity of their repertoires, our estimated inter-sample structure was
      consistent with the structure estimated by previous methods based on abundance or
      overlapping sequence information. For the dataset of human healthy donors and
      Sezary syndrome patients, our method also showed robust estimation performance
      even under the condition of high sparsity in TCR sequences, while previous
      studies failed to estimate the structure. In addition, we identified the
      sequences that contribute to the pairwise-sample differences between the
      repertoires with the different genetic backgrounds of mice. Such identification
      of the sequences contributing to variation in immune cell repertoires may provide
      substantial insight for the development of new immunotherapies and vaccines.

PMID- 29187850
TI  - Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and
      Systemic and Vascular Inflammation in Obesity and Diabetes.
AB  - Purpose: Obesity is a major modifiable risk factor for cardiovascular disease.
      Bariatric surgery is considered to be the most effective treatment option for
      weight reduction in obese patients with and without type 2 diabetes (T2DM).
      Objective: To evaluate changes in lipoproteins, insulin resistance, mediators of
      systemic and vascular inflammation, and endothelial dysfunction following Roux-en
      Y bariatric surgery in obese patients with and without diabetes. Materials and
      methods: Lipoproteins, insulin resistance, mediators of systemic and vascular
      inflammation, and endothelial dysfunction were measured in 37 obese patients with
      (n = 17) and without (n = 20) T2DM, before and 6 and 12 months after Roux-en-Y
      bariatric surgery. Two way between subject ANOVA was carried out to study the
      interaction between independent variables (time since surgery and presence of
      diabetes) and all dependent variables. Results: There was a significant effect of
      time since surgery on (large effect size) weight, body mass index (BMI), waist
      circumference, triglycerides (TG), small-dense LDL apolipoprotein B (sdLDL ApoB),
      HOMA-IR, CRP, MCP-1, ICAM-1, E-selectin, P-selectin, leptin, and adiponectin. BMI
      and waist circumference had the largest impact of time since surgery. The effect
      of time since surgery was noticed mostly in the first 6 months. Absence of
      diabetes led to a significantly greater reduction in total cholesterol, low
      density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol
      although the effect size was small to medium. There was a greater reduction in TG
      and HOMA-IR in patients with diabetes with a small effect size. No patients were
      lost to follow up. Conclusion: Lipoproteins, insulin resistance, mediators of
      systemic and vascular inflammation, and endothelial dysfunction improve mostly 6
      months after bariatric surgery in obese patients with and without diabetes.
      Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02169518.
      https://clinicaltrials.gov/ct2/show/NCT02169518?term=paraoxonase&cntry1=EU%3AGB&r
      nk=1.

PMID- 29187852
TI  - Editorial: Allorecognition by Leukocytes of the Adaptive Immune System.

PMID- 29187851
TI  - Modulation of P2X7 Receptor during Inflammation in Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is characterized by macrophage accumulation and
      inflammatory infiltrates into the CNS contributing to demyelination. Because
      purinergic P2X7 receptor (P2X7R) is known to be abundantly expressed on cells of
      the hematopoietic lineage and of the nervous system, we further investigated its
      phenotypic expression in MS and experimental autoimmune encephalomyelitis
      conditions. By quantitative reverse transcription polymerase chain reaction and
      flow cytometry, we analyzed the P2X7R expression in human mononuclear cells of
      peripheral blood from stable and acute relapsing-remitting MS phases. Human
      monocytes were also challenged in vitro with pro-inflammatory stimuli such as the
      lipopolysaccharide, or the P2X7R preferential agonist 2'(3')-O-(4
      Benzoylbenzoyl)adenosine 5'-triphosphate, before evaluating P2X7R protein
      expression. Finally, by immunohistochemistry and immunofluorescence confocal
      analysis, we investigated the P2X7R expression in frontal cortex from secondary
      progressive MS cases. We demonstrated that P2X7R is present and inhibited on
      peripheral monocytes isolated from MS donors during the acute phase of the
      disease, moreover it is down-regulated in human monocytes after pro-inflammatory
      stimulation in vitro. P2X7R is instead up-regulated on astrocytes in the
      parenchyma of frontal cortex from secondary progressive MS patients,
      concomitantly with monocyte chemoattractant protein-1 chemokine, while totally
      absent from microglia/macrophages or oligodendrocytes, despite the occurrence of
      inflammatory conditions. Our results suggest that inhibition of P2X7R on
      monocytes and up-regulation in astrocytes might contribute to sustain
      inflammatory mechanisms in MS. By acquiring further knowledge about P2X7R
      dynamics and identifying P2X7R as a potential marker for the disease, we expect
      to gain insights into the molecular pathways of MS.

PMID- 29187853
TI  - Fine-Tuning of Optimal TCR Signaling in Tumor-Redirected CD8 T Cells by Distinct
      TCR Affinity-Mediated Mechanisms.
AB  - Redirecting CD8 T cell immunity with self/tumor-specific affinity-matured T cell
      receptors (TCRs) is a promising approach for clinical adoptive T cell therapy,
      with the aim to improve treatment efficacy. Despite numerous functional-based
      studies, little is known about the characteristics of TCR signaling (i.e.,
      intensity, duration, and amplification) and the regulatory mechanisms underlying
      optimal therapeutic T cell responses. Using a panel of human SUP-T1 and primary
      CD8 T cells engineered with incremental affinity TCRs against the cancer-testis
      antigen NY-ESO-1, we found that upon activation, T cells with optimal-affinity
      TCRs generated intense and sustained proximal (CD3zeta, LCK) signals associated
      with distal (ERK1/2) amplification-gain and increased function. In contrast, in T
      cells with very high affinity TCRs, signal initiation was rapid and strong yet
      only transient, resulting in poor MAPK activation and low proliferation potential
      even at high antigen stimulation dose. Under resting conditions, the levels of
      surface TCR/CD3epsilon, CD8beta, and CD28 expression and of CD3zeta
      phosphorylation were significantly reduced in those hyporesponsive cells,
      suggesting the presence of TCR affinity-related activation thresholds. We also
      show that SHP phosphatases were involved along the TCR affinity gradient, but
      displayed spatially distinct regulatory roles. While PTPN6/SHP-1 phosphatase
      activity controlled TCR signaling initiation and subsequent amplification by
      counteracting CD3zeta and ERK1/2 phosphorylation, PTPN11/SHP-2 augmented MAPK
      activation without affecting proximal TCR signaling. Together, our findings
      indicate that optimal TCR signaling can be finely tuned by TCR affinity-dependent
      SHP-1 and SHP-2 activity, and this may readily be determined at the TCR/CD3
      complex level. We propose that these TCR affinity-associated regulations
      represent potential protective mechanisms preventing high affinity TCR-mediated
      autoimmune diseases.

PMID- 29187854
TI  - An Analysis of Natural T Cell Responses to Predicted Tumor Neoepitopes.
AB  - Personalization of cancer immunotherapies such as therapeutic vaccines and
      adoptive T-cell therapy may benefit from efficient identification and targeting
      of patient-specific neoepitopes. However, current neoepitope prediction methods
      based on sequencing and predictions of epitope processing and presentation result
      in a low rate of validation, suggesting that the determinants of peptide
      immunogenicity are not well understood. We gathered published data on human
      neopeptides originating from single amino acid substitutions for which T cell
      reactivity had been experimentally tested, including both immunogenic and non
      immunogenic neopeptides. Out of 1,948 neopeptide-HLA (human leukocyte antigen)
      combinations from 13 publications, 53 were reported to elicit a T cell response.
      From these data, we found an enrichment for responses among peptides of length 9.
      Even though the peptides had been pre-selected based on presumed likelihood of
      being immunogenic, we found using NetMHCpan-4.0 that immunogenic neopeptides were
      predicted to bind significantly more strongly to HLA compared to non-immunogenic
      peptides. Investigation of the HLA binding strength of the immunogenic peptides
      revealed that the vast majority (96%) shared very strong predicted binding to HLA
      and that the binding strength was comparable to that observed for pathogen
      derived epitopes. Finally, we found that neopeptide dissimilarity to self is a
      predictor of immunogenicity in situations where neo- and normal peptides share
      comparable predicted binding strength. In conclusion, these results suggest new
      strategies for prioritization of mutated peptides, but new data will be needed to
      confirm their value.

PMID- 29187855
TI  - CD4-Binding Site Directed Cross-Neutralizing scFv Monoclonals from HIV-1 Subtype
      C Infected Indian Children.
AB  - Progression of human immunodeficiency virus type-1 (HIV-1) infection in children
      is faster than adults. HIV-1 subtype C is responsible for more than 50% of the
      infections globally and more than 90% infections in India. To date, there is no
      effective vaccine against HIV-1. Recent animal studies and human Phase I trials
      showed promising results of the protective effect of anti-HIV-1 broadly
      neutralizing antibodies (bnAbs). Interaction between CD4 binding site (CD4bs) on
      the HIV-1 envelope glycoprotein and CD4 receptor on the host immune cells is the
      primary event leading to HIV-1 infection. The CD4bs is a highly conserved region,
      comprised of a conformational epitope, and is a potential target of bnAbs such as
      VRC01 that is presently under human clinical trials. Recombinant scFvs can access
      masked epitopes due to their small size and have shown the potential to inhibit
      viral replication and neutralize a broad range of viruses. Pediatric viruses are
      resistant to many of the existing bnAbs isolated from adults. Therefore, in this
      study, pooled peripheral blood mononuclear cells from 9 chronically HIV-1 subtype
      C infected pediatric cross-neutralizers whose plasma antibodies exhibited potent
      and cross-neutralizing activity were used to construct a human anti-HIV-1 scFv
      phage library of 9 * 108 individual clones. Plasma mapping using CD4bs-specific
      probes identified the presence of CD4bs directed antibodies in 4 of these
      children. By extensive biopanning of the library with CD4bs-specific antigen RSC3
      core protein, we identified two cross-neutralizing scFv monoclonals 2B10 and 2E4
      demonstrating a neutralizing breadth and GMT of 77%, 17.9 ug/ml and 32%, 51.2
      ug/ml, respectively, against a panel of 49 tier 1, 2 and 3 viruses. Both scFvs
      competed with anti-CD4bs bnAb VRC01 confirming their CD4bs epitope specificity.
      The 2B10 scFv was effective in neutralizing the 7 subtype C and subtype A
      pediatric viruses tested. Somatic hypermutations in the VH gene of scFvs (10.1
      11.1%) is comparable with that of the adult antibodies. These cross-neutralizing
      CD4bs-directed scFvs can serve as potential reagents for passive immunotherapy. A
      combination of cross-neutralizing scFvs of diverse specificities with
      antiretroviral drugs may be effective in suppressing viremia at an early stage of
      HIV-1 infection and prevent disease progression.

PMID- 29187856
TI  - A Role for Iodide and Thyroglobulin in Modulating the Function of Human Immune
      Cells.
AB  - Iodine is an essential element required for the function of all organ systems.
      Although the importance of iodine in thyroid hormone synthesis and reproduction
      is well known, its direct effects on the immune system are elusive. Human
      leukocytes expressed mRNA of iodide transporters (NIS and PENDRIN) and thyroid
      related proteins [thyroglobulin (TG) and thyroid peroxidase (TPO)]. The mRNA
      levels of PENDRIN and TPO were increased whereas TG transcripts were decreased
      post leukocyte activation. Flow cytometric analysis revealed that both PENDRIN
      and NIS were expressed on the surface of leukocyte subsets with the highest
      expression occurring on monocytes and granulocytes. Treatment of leukocytes with
      sodium iodide (NaI) resulted in significant changes in immunity-related
      transcriptome with an emphasis on increased chemokine expression as probed with
      targeted RNASeq. Similarly, treatment of leukocytes with NaI or Lugol's iodine
      induced increased protein production of both pro- and anti-inflammatory
      cytokines. These alterations were not attributed to iodide-induced de novo
      thyroid hormone synthesis. However, upon incubation with thyroid-derived TG,
      primary human leukocytes but not Jurkat T cells released thyroxine and
      triiodothyronine indicating that immune cells could potentially influence thyroid
      hormone balance. Overall, our studies reveal the novel network between human
      immune cells and thyroid-related molecules and highlight the importance of iodine
      in regulating the function of human immune cells.

PMID- 29187857
TI  - Editorial: On the Origin and Function of Human NK-Like CD8+ T Cells: Charting New
      Territories.

PMID- 29187858
TI  - Domestication Genomics of the Open-Pollinated Scarlet Runner Bean (Phaseolus
      coccineus L.).
AB  - The runner bean is a legume species from Mesoamerica closely related to common
      bean (Phaseolus vulgaris). It is a perennial species, but it is usually
      cultivated in small-scale agriculture as an annual crop for its dry seeds and
      edible immature pods. Unlike the common bean, P. coccineus has received little
      attention from a genetic standpoint. In this work we aim to (1) provide
      information about the domestication history and domestication events of P.
      coccineus; (2) examine the distribution and level of genetic diversity in wild
      and cultivated Mexican populations of this species; and, (3) identify candidate
      loci to natural and artificial selection. For this, we generated genotyping by
      sequencing data (42,548 SNPs) from 242 individuals of P. coccineus and the
      domesticated forms of the closely related species P. vulgaris (20) and P. dumosus
      (35). Eight genetic clusters were detected, of which half corresponds to wild
      populations and the rest to domesticated plants. The cultivated populations
      conform a monophyletic clade, suggesting that only one domestication event
      occurred in Mexico, and that it took place around populations of the Trans
      Mexican Volcanic Belt. No difference between wild and domesticated levels of
      genetic diversity was detected and effective population sizes are relatively
      high, supporting a weak genetic bottleneck during domestication. Most populations
      presented an excess of heterozygotes, probably due to inbreeding depression. One
      population of P. coccineus subsp. striatus had the greatest excess and seems to
      be genetically isolated despite being geographically close to other wild
      populations. Contrasting with previous studies, we did not find evidence of
      recent gene flow between wild and cultivated populations. Based on outlier
      detection methods, we identified 24 domestication-related SNPs, 13 related to
      cultivar diversification and eight under natural selection. Few of these SNPs
      fell within annotated loci, but the annotated domestication-related SNPs are
      highly expressed in flowers and pods. Our results contribute to the understanding
      of the domestication history of P. coccineus, and highlight how the genetic
      signatures of domestication can be substantially different between closely
      related species.

PMID- 29187860
TI  - Identification of Candidate Genes for Calcium and Magnesium Accumulation in
      Brassica napus L. by Association Genetics.
AB  - Calcium (Ca) and magnesium (Mg) are essential plant nutrients and vital for human
      and animal nutrition. Biofortification of crops has previously been suggested to
      alleviate widespread human Ca and Mg deficiencies. In this study, new candidate
      genes influencing the leaf accumulation of Ca and Mg were identified in young
      Brassica napus plants using associative transcriptomics of ionomics datasets. A
      total of 247 and 166 SNP markers were associated with leaf Ca and Mg
      concentration, respectively, after false discovery rate correction and removal of
      SNPs with low second allele frequency. Gene expression markers at similar
      positions were also associated with leaf Ca and Mg concentration, including loci
      on chromosomes A10 and C2, within which lie previously identified transporter
      genes ACA8 and MGT7. Further candidate genes were selected from seven loci and
      the mineral composition of whole Arabidopsis thaliana shoots were characterized
      from lines mutated in orthologous genes. Four and two mutant lines had reduced
      shoot Ca and Mg concentration, respectively, compared to wild type plants. Three
      of these mutations were found to have tissue specific effects; notably reduced
      silique Ca in all three such mutant lines. This knowledge could be applied in
      targeted breeding, with the possibility of increasing Ca and Mg in plant tissue
      for improving human and livestock nutrition.

PMID- 29187859
TI  - A Review of Biotechnological Artemisinin Production in Plants.
AB  - Malaria is still an eminent threat to major parts of the world population mainly
      in sub-Saharan Africa. Researchers around the world continuously seek novel
      solutions to either eliminate or treat the disease. Artemisinin, isolated from
      the Chinese medicinal herb Artemisia annua, is the active ingredient in
      artemisinin-based combination therapies used to treat the disease. However,
      naturally artemisinin is produced in small quantities, which leads to a shortage
      of global supply. Due to its complex structure, it is difficult chemically
      synthesize. Thus to date, A. annua remains as the main commercial source of
      artemisinin. Current advances in genetic and metabolic engineering drives to more
      diverse approaches and developments on improving in planta production of
      artemisinin, both in A. annua and in other plants. In this review, we describe
      efforts in bioengineering to obtain a higher production of artemisinin in A.
      annua and stable heterologous in planta systems. The current progress and
      advancements provides hope for significantly improved production in plants.

PMID- 29187861
TI  - Transcriptome-Wide Identification and Characterization of MYB Transcription
      Factor Genes in the Laticifer Cells of Hevea brasiliensis.
AB  - MYB transcription factors hold vital roles in the regulation of plant secondary
      metabolic pathways. Laticifers in rubber trees (Hevea brasiliensis) are of
      primary importance in natural rubber production because natural rubber is formed
      and stored within these structures. To understand the role of MYB transcription
      factors in the specialized cells, we identified 44 MYB genes (named HblMYB1 to
      HblMYB44) by using our previously obtained transcriptome database of rubber tree
      laticifer cells and the public rubber tree genome database. Expression profiles
      showed that five MYB genes were highly expressed in the laticifers. HblMYB19 and
      HblMYB44 were selected for further study. HblMYB19 and HblMYB44 bound the
      promoters of HbFDPS1, HbSRPP, and HRT1 in yeast. Furthermore, the transient
      overexpression of HblMYB19 and HblMYB44 in tobacco plants significantly increased
      the activity of the promoters of HbFDPS1, HbSRPP, and HRT1. Basing on this
      information, we proposed that HblMYB19 and HblMYB44 are the regulators of
      HbFDPS1, HbSRPP, and HRT1, which are involved in the biosynthesis pathway of
      natural rubber.

PMID- 29187862
TI  - Identifying Chloris Species from Cuban Citrus Orchards and Determining Their
      Glyphosate-Resistance Status.
AB  - The Chloris genus is a C4 photosynthetic species mainly distributed in tropical
      and subtropical regions. Populations of three Chloris species occurring in citrus
      orchards from central Cuba, under long history glyphosate-based weed management,
      were studied for glyphosate-resistant status by characterizing their herbicide
      resistance/tolerance mechanisms. Morphological and molecular analyses allowed
      these species to be identified as C. ciliata Sw., Chloris elata Desv., and
      Chloris barbata Sw. Based on the glyphosate rate that causes 50% mortality of the
      treated plants, glyphosate resistance (R) was confirmed only in C. elata, The R
      population was 6.1-fold more resistant compared to the susceptible (S)
      population. In addition, R plants of C. elata accumulated 4.6-fold less shikimate
      after glyphosate application than S plants. Meanwhile, populations of C. barbata
      and C. ciliata with or without glyphosate application histories showed similar
      LD50 values and shikimic acid accumulation rates, demonstrating that resistance
      to glyphosate have not evolved in these species. Plants of R and S populations of
      C. elata differed in 14C-glyphosate absorption and translocation. The R
      population exhibited 27.3-fold greater 5-enolpyruvyl shikimate-3-phosphate
      synthase (EPSPS) activity than the S population due to a target site mutation
      corresponding to a Pro-106-Ser substitution found in the EPSPS gene. These
      reports show the innate tolerance to glyphosate of C. barbata and C. ciliata, and
      confirm the resistance of C. elata to this herbicide, showing that both non
      target site and target-site mechanisms are involved in its resistance to
      glyphosate. This is the first case of herbicide resistance in Cuba.

PMID- 29187864
TI  - Editorial: Cancer Diagnostic and Therapeutic Target Identification and
      Verification Based on the Regulatory Functions of MicroRNAs.

PMID- 29187863
TI  - Smooth, an hnRNP-L Homolog, Might Decrease Mitochondrial Metabolism by Post
      Transcriptional Regulation of Isocitrate Dehydrogenase (Idh) and Other Metabolic
      Genes in the Sub-Acute Phase of Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) can cause persistent pathological alteration of
      neurons. This may lead to cognitive dysfunction, depression and increased
      susceptibility to life threatening diseases, such as epilepsy and Alzheimer's
      disease. To investigate the underlying genetic and molecular basis of TBI, we
      subjected w1118Drosophila melanogaster to mild closed head trauma and found that
      mitochondrial activity is reduced in the brains of these flies 24 h after
      inflicting trauma. To determine the transcriptomic changes after mild TBI, we
      collected fly heads 24 h after inflicting trauma, and performed RNA-seq analyses.
      Classification of alternative splicing changes showed selective retention (RI) of
      long introns (>81 bps), with a mean size of ~3,000 nucleotides. Some of the genes
      containing RI showed a significant reduction in transcript abundance and are
      involved in mitochondrial metabolism such as Isocitrate dehydrogenase (Idh),
      which makes alpha-KG, a co-factor needed for both DNA and histone demethylase
      enzymes. The long introns are enriched in CA-rich motifs known to bind to Smooth
      (Sm), a heterogeneous nuclear ribonucleoprotein L (hnRNP-L) class of splicing
      factor, which has been shown to interact with the H3K36 histone
      methyltransferase, SET2, and to be involved in intron retention in human cells.
      H3K36me3 is a histone mark that demarcates exons in genes by interacting with the
      mRNA splicing machinery. Mutating sm (sm4/Df) resulted in loss of both basal and
      induced levels of RI in many of the same long-intron containing genes. Reducing
      the levels of Kdm4A, the H3K36me3 histone demethylase, also resulted in loss of
      basal levels of RI in many of the same long-intron containing genes. Chromatin
      immunoprecipitation followed by deep sequencing (ChIP-seq) for H3K36me3 revealed
      increased levels of this histone modification in retained introns post-trauma at
      CA-rich motifs. Based on these results, we propose a model in which TBI
      temporarily decreases mitochondrial activity in the brain 24 h after inflicting
      trauma, which decreases alpha-KG levels, and increases H3K36me3 levels and intron
      retention of long introns by decreasing Kdm4A activity. The consequent reduction
      in mature mRNA levels in metabolism genes, such as Idh, further reduces alpha-KG
      levels in a negative feedback loop. We further propose that decreasing metabolism
      after TBI in such a manner is a protective mechanism that gives the brain time to
      repair cellular damage induced by TBI.

PMID- 29187865
TI  - A novel method of nicotine quantification in electronic cigarette liquids and
      aerosols.
AB  - The electronic cigarette (e-cigarette) has emerged as popular electronic nicotine
      delivery devices (ENDs). However, the general safety and validity of e-cigarettes
      for nicotine delivery efficacy are still not well understood. This study
      developed a new method for efficient measurement of nicotine levels in both the
      liquids (e-liquids) used in e-cigarettes and the aerosols generated from the e
      cigarettes. Protonation of the pyrrolidine nitrogen of nicotine molecules by
      addition of excess hydrochloric acid affords an aminium salt that is readily
      quantified by Fourier transform ion cyclotron mass spectrometry (FT-ICR-MS). The
      kinetics of nicotine protonation was studied using 1H NMR spectroscopy.
      Quantitative analyses of nicotine in commercial e-liquids and in the
      corresponding derived e-cigarette aerosols were carried out using direct infusion
      FT-ICR-MS. The 1H NMR study of nicotine protonation revealed a first order
      reaction and an activation energy of 30.05 kJ mol-1. The nicotine levels measured
      in the commercial e-liquids were within a wide and highly variable range of 
      2.94% to +25.20% around the manufacturer's stated values. The results indicated
      considerable differences between the measured levels and the advertised levels of
      nicotine in the e-liquids. The nicotine quantity measured in aerosols increased
      linearly both with nicotine level in e-liquids (same number of puffs) and with
      number of puffs (same e-liquids). These data show that quality control of e
      liquids and use characteristics are major variables in efficacy of nicotine
      delivery.

PMID- 29187866
TI  - Modification of proteolytic activity matrix analysis (PrAMA) to measure ADAM10
      and ADAM17 sheddase activities in cell and tissue lysates.
AB  - Increases in expression of ADAM10 and ADAM17 genes and proteins have been
      evaluated, but not validated as cancer biomarkers. Specific enzyme activities
      better reflect enzyme cellular functions, and might be better biomarkers than
      enzyme genes or proteins. However, no high throughput assay is available to test
      this possibility. Recent studies have developed the high throughput real-time
      proteolytic activity matrix analysis (PrAMA) that integrates the enzymatic
      processing of multiple enzyme substrates with mathematical-modeling computation.
      The original PrAMA measures with significant accuracy the activities of
      individual metalloproteinases expressed on live cells. To make the biomarker
      assay usable in clinical practice, we modified PrAMA by testing enzymatic
      activities in cell and tissue lysates supplemented with broad-spectrum non-MP
      enzyme inhibitors, and by maximizing the assay specificity using systematic
      mathematical-modeling analyses. The modified PrAMA accurately measured the
      absence and decreases of ADAM10 sheddase activity (ADAM10sa) and ADAM17sa in
      ADAM10-/- and ADAM17-/- mouse embryonic fibroblasts (MEFs), and ADAM10- and
      ADAM17-siRNA transfected human cancer cells, respectively. It also measured the
      restoration and inhibition of ADAM10sa in ADAM10-cDNA-transfected ADAM10-/- MEFs
      and GI254023X-treated human cancer cell and tissue lysates, respectively.
      Additionally, the modified PrAMA simultaneously quantified with significant
      accuracy ADAM10sa and ADAM17sa in multiple human tumor specimens, and showed the
      essential characteristics of a robust high throughput multiplex assay that could
      be broadly used in biomarker studies. Selectively measuring specific enzyme
      activities, this new clinically applicable assay is potentially superior to the
      standard protein- and gene-expression assays that do not distinguish active and
      inactive enzyme forms.

PMID- 29187867
TI  - FAM13A as a Novel Hypoxia-Induced Gene in Non-Small Cell Lung Cancer.
AB  - : Several genome-wide association studies (GWASs), have identified that FAM13A
      and IREB2 loci are associated with lung cancer, but the mechanisms by which these
      genes contribute to lung diseases susceptibility, especially in hypoxia context,
      are unknown. Hypoxia has been identified as a major negative factor for tumor
      progression in clinical observation. It has been suggested, that lower oxygen
      tension, may modulate the IREB2 and FAM13A activity. However, the role of these
      genes in hypoxia response has not been explained. To precise the role of these
      genes in hypoxia response, we analyzed the FAM13A and IREB2 expression, in lung
      cancer cells in vitro and lung cancer tissue fragments cultured ex vivo. Three
      cell lines: non-small cell lung cancer (A549, CORL-105), human lung fibroblasts
      (HL) and 37 lung cancer tissue fragments were analyzed. The expression of IREB2,
      FAM13A and HIF1alpha after sustained 72 hours of hypoxia versus normal oxygen
      concentration were analyzed by TaqMan(r) Gene Expression Assays and Western Blot.
      The expression of FAM13A was significantly up-regulated by hypoxia in two lung
      cancer cell lines (A549, CORL-105, P<0.001), both at the level of protein and
      mRNA, and in lung cancer tissue fragments (P=0.0004). The IREB2 was down
      regulated after hypoxia in A549 cancer cells (P<0.001). CONCLUSIONS: We found
      that FAM13A overexpression in human lung cancer cell lines overlapped with
      hypoxia effect on lung cancer tissues. FAM13A is strongly induced by hypoxia and
      may be identified as a novel hypoxia-induced gene in non-small cell lung cancer.

PMID- 29187868
TI  - Cisplatin Nephrotoxicity Might Have a Sex Difference. An analysis Based on
      Women's Sex Hormone Changes.
AB  - Background: A sex difference in cisplatin-induced nephrotoxicity (CIN) has been
      reported in human and animal studies. We examined in humans whether it is
      associated with sex-hormone changes. Methods: In this retrospective nationwide
      cohort study, we used Taiwan's National Health Insurance Research Database
      (NHIRD) to identify patients with a history of malignancy and cisplatin
      treatment. Patients diagnosed with kidney disease before cisplatin treatment and
      those with sex-organ malignancies were excluded. A diagnosis of kidney disease
      within 90 days after the first administration of cisplatin was the study outcome.
      Risk factors were estimated using a Cox regression model. Subgroup analyses were
      performed based on different women's estrogen levels in phases of childbearing,
      perimenopause, and postmenopause. Results: A retrospective analysis of the
      records of 3973 men (mean age: 56.15 +/- 12.85 years) and 1154 women (mean age:
      56.31 +/- 12.40 years) showed that 1468 (36.95%) men and 451 (39.08%) women had a
      new diagnosis of kidney disease. The risk factors were being > 55 years old, a
      high comorbidity score, and a history of aminoglycoside treatment. Only
      postmenopausal women had a significantly higher risk of kidney injury (hazard
      ratio: 1.28; 95% CI: 1.02-1.61) than did men. Conclusions: Perimenopausal women
      have a significantly higher risk of CIN than do men, which might be explained by
      women's higher levels of estrogen. Additional studies on the underlying
      mechanisms of the sex difference of CIN are needed.

PMID- 29187869
TI  - Fuzi Enhances Anti-Tumor Efficacy of Radiotherapy on Lung Cancer.
AB  - In traditional Chinese medicine, Fuzi is widely used as an antitumor agent or an
      adjuvant medication combined with radiotherapy and chemotherapy, but its
      mechanism remains unclear. In this study, we investigated anti-tumor and
      immunoregulation efficacy of Fuzi combined with radiotherapy in mice with Lewis
      lung cancer (LLC). We found that Fuzi combined with radiotherapy significantly
      inhibited the growth of LLC, promoted the apoptosis of cancer cells, and
      prolonged the survival of mice with LLC. Mechanistically, we found that Fuzi
      decreased the proportion of Treg cells, reduced serum levels of cytokines such as
      interleukin (IL)-10 and transforming growth factor (TGF)-beta, and downregulated
      the expression of programmed death ligand-1 in mice with LLC subjected to
      radiotherapy. This study suggests that Fuzi has immunomodulation function to act
      as radiosensitizer and improve radiotherapy against lung cancer.

PMID- 29187870
TI  - Ectopic Expression of Snail and Twist in Ph+ Leukemia Cells Upregulates CD44
      Expression and Alters Their Differentiation Potential.
AB  - Philadelphia chromosome-positive (Ph+) leukemia is characterized by reciprocal
      translocation between chromosomes 9 and 22. The resultant BCR/ABL fusion protein
      displays constitutive tyrosine kinase activity, leading to the induction of
      aberrant proliferation and neoplastic transformation. The bone marrow (BM)
      microenvironment is tumor-promoting, and contributes to disease recurrence in Ph+
      leukemia. Activity in the BM microenvironment is mediated by several cellular
      compartments, extracellular matrix, various soluble factors including
      transforming growth factor beta 1 (TGF-beta1), and the hypoxic conditions in the
      BM niche. TGF-beta1 is released during bone remodeling and plays a role in
      maintaining leukemic stem cells, as well as being implicated in the epithelial
      mesenchymal transition (EMT) process in most solid tumors. Although EMT is
      largely implicated in epithelial tumors, recent findings argue for an EMT-like
      process in leukemia as well. The surface receptor CD44 is involved in cell
      adhesion, cell migration, and homing of normal and malignant hematopoietic stem
      cells. Elevation of CD44 expression is considered a marker for a worse prognosis
      in most hematological malignancies. We explored the functions of Snail and Twist1
      in Ph+ leukemia. We showed that ectopic expression of Snail and, to a lesser
      extent, Twist1, upregulates CD44 expression that is beta-catenin-dependent.
      Moreover, the presence of Snail or Twist1 partially blocked phorbol 12-myristate
      13-acetate-induced megakaryocyte differentiation, while that of Twist
      significantly altered imatinib-induced erythroid differentiation. Thus EMT
      modulators affected proliferation, CD44 gene expression and differentiation
      ability of Ph+ leukemia cells.

PMID- 29187871
TI  - Local surgical excision versus endoscopic resection for rectal carcinoid: A meta
      analysis.
AB  - Purpose: To date, there is not enough evidence concerning the optimal treatment
      strategy for early rectal carcinoids, we conducted a meta-analysis in order to
      determine the feasible local treatment for these selected patients. Methods: We
      searched the studies from the PubMed, Cochrane database, Medline, Ovid,
      SpringerLink, PMC and Embase between January 2007 and April 2017. Studies of
      local surgical excision compared with endoscopic resection for rectal carcinoids
      less than 20mm without adverse features were included. Data were analyzed by
      using Stata SE 12.0. Results: Seven studies were included in this meta-analysis,
      with a total of 1056 patients. The data showed that local surgical excision was
      associated with higher complete resection rate than that of endoscopic resection
      (OR 5.837, 95%CI 2.048 to 16.632, P=0.001) but consuming longer procedural time
      (SMD 1.757, 95% CI 1.263 to 2.251, P=0.000). Additionally, incidences of
      recurrence and en bloc resection rate were comparable between two kinds of
      resections. The difference of post-operative complications remained unclear.
      Conclusions: For rectal carcinoids sized 20mm or smaller without adverse
      features, endoscopic resection might be an efficient treatment, which achieved a
      comparable oncological safety as local surgical excision.

PMID- 29187872
TI  - Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer
      Patients.
AB  - Background and aims: There is no established predictive marker for the treatment
      of renal cancer. Metastatic renal cell carcinoma (mRCC) patients are often
      treated with sunitinib, a tyrosine kinase inhibitor. Sunitinibs anti-cancer
      effect is at least partly mediated through interfering with angiogenesis. Our aim
      with the current study was to assess annexin A1 (ANXA1), which stimulates
      angiogenesis, as a predictive marker for sunitinib therapy in mRCC patients.
      Since previous studies have indicated a predictive potential for cubilin, we also
      investigated the predictivity of ANXA1 combined with cubilin. Methods: ANXA1
      expression was analysed in tumor tissue from a cohort of patients with advanced
      RCC (n=139) using immunohistochemistry. Ninety-nine of the patients were treated
      with sunitinib in the first or second-line setting. Twenty-two of these were
      censored because of toxicity leading to the termination of treatment and the
      remaining (n=77) were selected for the present study. Results: Twenty-five (32%)
      out of seventy-seven of the tumors lacked ANXA1 in the cytoplasm. On statistical
      analyses using Kaplan-Meier method, aNXA1 negative tumors were significantly
      associated with a longer treatment benefit in terms of progression free survival
      (PFS). Overall survival was also significantly better for patients with ANXA1
      negative tumors. The combined ANXA1 positive and cubilin negative expression
      could more accurately than ANXA1 alone define the group not benefitting from
      treatment. Conclusions: Our results indicate that cytoplasmic expression of ANXA1
      is a negative predictive marker for sunitinib therapy in mRCC patients. A
      possible explanation for this finding is that sunitinibs anti-angiogenic effect
      cannot overcome the pro-angiogenic drive from many ANXA1 proteins.

PMID- 29187873
TI  - Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early
      Hepatocellular Carcinoma Recurrence?
AB  - Purpose: Serotonin (5-hydroxytryptamine, 5-HT) is well known for its growth
      stimulatory effect on several types of carcinoma and tumor cells. Since a large
      portion of 5-HT is stored and transported by platelets, the aim of this study was
      to assess the influence of platelet-sequestered 5-HT on post-resection
      hepatocellular carcinoma (HCC) recurrence. Methods: This pilot study was
      conducted in a cohort of forty patients diagnosed with HCC undergoing partial
      hepatectomy. 5-HT levels in serum, plasma and intra-platelet (IP) were monitored
      preoperatively and four weeks after liver resection. The patients were followed
      every three months after the surgery. Results: Follow-up was standardized to a
      fixed length of time. Fifteen patients (37.5%) developed HCC recurrence during 18
      months follow-up. Patients with recurrence had significantly reduced serum and IP
      5-HT levels at four weeks of liver resection (P = 0.003 and P = 0.014
      respectively). Accordingly, in the Cox regression hazard model, serum and IP 5-HT
      were able to independently predict the recurrence (hazard ratio = 0.1, 95%
      confidence interval = 0.01 - 0.75 and hazard ratio = 0.1, 95% confidence interval
      = 0.01 - 0.89 respectively). The optimal cut-off value of 42.77 ng/ml for serum
      [area under the curve (AUC): 0.78, P = 0.003] and 0.3117 ng per 106 platelets
      (AUC: 0.733, P = 0.015), on receiver operating characteristic (ROC) curve
      corresponded to maximum sensitivity and specificity of prediction. The disease
      free interval was significantly worse in patients with low serum and IP 5-HT (P =
      0.001 and P = 0.029 respectively). Conclusion: IP 5-HT monitored during early
      follow-up, after liver resection may represent a useful marker of early HCC
      recurrence.

PMID- 29187874
TI  - Albumin and Fibrinogen Combined Prognostic Grade Predicts Prognosis of Patients
      with Prostate Cancer.
AB  - Background: The nutritional status and systemic inflammation are thought to be
      associated with outcome in multiple types of cancer. The objective of this study
      was to determine the prognostic value of pretreatment albumin and fibrinogen
      combined prognostic grade (AFPG) in prostate cancer (PCa). Methods: 462 prostate
      cancer patients who had undergone androgen deprivation therapy (ADT) as first
      line therapy at four cencters were retrospectively analyzed. The serum albumin
      levels and plasma fibrinogen levels were measured at the time of diagnosis. The
      AFPG was calculated according to albumin and fibrinogen levels dichotomized by
      optimal cut-off values or clinical reference values. Univariate and multivariate
      cox regression analyses were performed to determine the associations of AFPG with
      progression-free survival (PFS), cancer-specific survival (CSS) and overall
      survival (OS). Prognostic accuracy was evaluated with the Harrell concordance
      index. Results: Multivariate analyses identified AFPG as an independent
      prognostic indicator for PFS, CSS and OS (each p < 0.01). According to optimal
      cut-off values, the addition of AFPG to the final models improved predictive
      accuracy for PFS, CSS and OS compared with the clinicopathological base models,
      which included Gleason score and incidence of metastasis. Moreover, AFPG
      according to optimal cut-off values was a better prognostic predictor than
      albumin levels alone or fibrinogen levels alone or AFPG according to clinical
      reference values. Conclusion: Decreased AFPG could predict a significantly poor
      prognosis in patients with PCa. Thus, we recommend adding AFPG according to
      optimal cut-off values to traditional prognostic model to improve the predictive
      accuracy.

PMID- 29187875
TI  - Prognostic Effect of Albumin-to-Globulin Ratio in Patients with solid tumors: A
      Systematic Review and Meta-analysis.
AB  - Background: Albumin and globulin are main components of serum protein. The level
      of albumin and globulin partially represents the nutrition status and immune
      system. Albumin-to-globulin ratio (AGR) has been reported as a prognostic factor
      in various cancers. We therefore performed a meta-analysis to elucidate the
      prognosis effect of AGR on survival outcomes in solid tumors. Method: Six
      electronic database were searched for the relevant articles that assessing the
      prognostic value of pre-treatment AGR in solid tumor patients. The primary
      outcome was overall survival (OS) and the secondary outcomes were cancer-specific
      survival (CSS), disease-free survival (DFS) and disease-metastasis-free survival
      (DMFS). The time-to-event outcomes were summarized in hazard ratio (HR) and 95%
      confidence interval (CI). Result: A total of 13890 solid tumor patients in 24
      studies were included. The AGR higher than the cut-off values ranging from 1.15
      1.75 was related to better OS (HR=0.58, 95%CI 0.537-0.626, p<0.0001), CSS
      (HR=0.287, 95%CI 0.187-0.438, p<0.0001), DFS (HR=0.792, 95%CI 0.715-0.878,
      p<0.0001) and DMFS (HR=0.595, 95%CI 0.447-0.792, p<0.0001). According to the cut
      off values, subgroup analysis showed that AGR had significant prognostic effect
      on OS in each cut-off intervals (<=1.20, 1.20-1.40 and >=1.40). Conclusion: Pre
      treatment AGR is an effective prognostic factor and high AGR represents an ideal
      clinical outcome in the solid tumor patients.

PMID- 29187876
TI  - Heteroplasmy and Copy Number Variations of Mitochondria in 88 Hepatocellular
      Carcinoma Individuals.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality
      worldwide. In this study, we had analysed the copy number variations and
      heteroplasmic mutations of mitochondria (MT) in 88 HCC individuals. The average
      copy number of MT genome in normal samples was significantly greater than that in
      tumor samples. Overall, the number of heteroplasmic mutations in 88 tumor and
      their matched normal samples were 241 and 173, respectively. There was higher
      positive ratio of heteroplasmic mutations in tumor samples (86%) than normal
      samples (73%). Worthwhile mention, ND1 gene harbored greater mutation frequency
      and more nonsynonymous mutations in tumor samples. Interestingly, 202 tumor
      specific heteroplasmic mutations were detected. Moreover, ND1, ND3, ND4, ND5 and
      ND6 genes had higher ratio of nonsynonymous versus synonymous mutations in tumor
      specific heteroplasmic mutations. It might suggest that the disorder of NADH
      dehydrogenase (complex I) resulted by heteroplasmic mutations may have close
      relation with tumorigenesis of hepatocellular carcinoma. This study provided
      theoretical basis for further understanding mechanism of tumorigenesis from the
      perspective of mitochondrial heteroplasmic mutations.

PMID- 29187877
TI  - Overexpression of CKAP4 is Associated with Poor Prognosis in Clear Cell Renal
      Cell Carcinoma and Functions via Cyclin B Signaling.
AB  - Aim: We aimed to study the role of CKAP4 in clear cell renal cell carcinoma
      (ccRCC), which is not reported previously. Method: In silico exploration and
      validation using immunohistochemistry in ccRCC samples were used to identify the
      impact of CKAP4 expression on clinicopathological parameters. In vitro and in
      vivo studies were carried out to recapitulate the role of CKAP4 in ccRCC cell
      lines and animal models. Results: Overexpression of CKAP4 occurred in 5% of ccRCC
      patients, who had significantly worsened prognosis. Increased CKAP4 expression
      was significantly associated with TNM staging and Fuhrman grade. Pathway analysis
      for genes coexpressed with CKAP4 in ccRCC unanimously revealed significant cell
      cycle progression at G2/M phase. Expressions of CCNB1 and CCNB2 were correlated
      with CKAP4 expression. Genetic upregulation of CKAP4 significantly increased
      proliferation, cell invasion and migration in ccRCC cell lines, and vice versa
      for CKAP4 silencing. CKAP4 silencing also significantly increased cell population
      at G2/M phase, while not influencing cell apoptosis. Silencing or upregulation of
      CKAP4 resulted in decreased or increased CCNB1/2 expressions, respectively.
      CCNB1/CDK1 inhibitor significantly inhibited colony formation ability and in vivo
      tumor growth of RCC cells with CKAP4 overexpression. Conclusion: Upregulation of
      CKAP4 was associated with worsened characteristics of ccRCC. CKAP4 was related
      with CCNB signaling in ccRCC, which supported a role for CCNB/CDK inhibitor for
      ccRCC with such genotype.

PMID- 29187878
TI  - UHRF1 is an Independent Prognostic Factor and a Potential Therapeutic Target of
      Esophageal Squamous Cell Carcinoma.
AB  - Purpose: Ubiquitin-like with plant homeodomain and ring-finger domains 1 (UHRF1)
      plays an essential role in DNA methylation, and the overexpression of UHRF1 is
      associated with poor prognosis in various cancers. Esophageal squamous cell
      carcinoma (ESCC) accounts for approximately 90% of esophageal cancer cases in
      China, but the five-year survival rate for patients is less than 10% due to
      limited clinical approaches for early diagnosis and treatment. The present
      research aimed to investigate the expression of UHRF1 in ESCC and its biological
      role in ESCC development. Methods: UHRF1 expression in ESCC and normal esophageal
      tissues was examined using immunohistochemical staining, followed by analysis of
      the correlation between UHRF1 expression and clinical features. In addition, the
      effects of lentivirus-mediated RNA interference of UHRF1 on global DNA
      methylation, cell proliferation, cell cycle progression and apoptosis and were
      investigated in ESCC cells. Results: UHRF1 was overexpressed in ESCC tissues and
      was an independent prognostic factor for ESCC patients. In ESCC cells, knockdown
      of UHRF1 caused global DNA hypomethylation, inhibited cell proliferation and
      induced apoptosis. Furthermore, UHRF1 depletion induced cell cycle arrest at the
      G2/M phase, accompanied by activation of Wee1 and DNA damage response pathway.
      Conclusions: Our findings identify UHRF1 as a promising prognostic marker for
      ESCC and suggest that UHRF1 may be a potential therapy target for ESCC patients
      with elevated UHRF1 expression.

PMID- 29187880
TI  - The PARP-1 inhibitor Olaparib suppresses BRCA1 protein levels, increases
      apoptosis and causes radiation hypersensitivity in BRCA1+/- lymphoblastoid cells.
AB  - The use of polyADPribose polymerase inhibitors in cancer treatment provides a
      unique opportunity to target DNA repair processes in cancer cells while leaving
      normal tissue intact. The PARP-1 enzyme repairs DNA single strand breaks (SSB).
      Therefore PARP-1 inhibition in BRCA1 negative cancers results in the formation of
      cytotoxic DNA double strand breaks (DSB) causing synthetic lethality. The use of
      PARP1 inhibitors is gaining momentum in the treatment of a variety of tumours
      with BRCA1 involvement including breast, ovarian, pancreatic and prostate cancer.
      Our previous work showed that the PARP-1 inhibitor Olaparib causes both
      hypersensitivity of BRCA1+/- cells following exposure to gamma radiation due to
      the persistence of DNA strand breaks in cells, measured by the DNA damage
      biomarker gamma-H2AX. Therefore dual treatment of cancers with radiotherapy and
      PARP1 inhibition may lead to cases of increased normal tissue toxicity in cancer
      patients. In this study we exposed two normal lymphoblastoid cell lines and three
      heterozygous BRCA1 lymphoblastoid cell lines to the PARP-1 inhibitor Olaparib and
      gamma radiation and after measured BRCA1 protein expression and apoptosis levels
      following treatment. BRCA1 protein foci analysis was performed on cells exposed
      to 2 Gy radiation in the presence or absence of 5 MUM Olaparib. Using
      immunofluorescence and imaging flow cytometry, foci were measured in untreated
      cells and at 0.5, 3, 5 and 24 hours post-irradiation. Exposing normal and BRCA1+/
      cells to Olaparib followed by gamma radiation results in a dramatic change in
      BRCA1 protein foci expression, with a significant reduction in BRCA1 protein
      expression observed in the heterozygote cells, together with an increase in
      apoptosis levels in these cells. In conclusion, combining PARP1 inhibitors with
      radiotherapy in treating of BRCA1-related cancers has clinical relevance, however
      this study and our previous publications serve to highlight the potential
      problems of increased side effects in these scenarios.

PMID- 29187879
TI  - Aberrant Expression of the Long Non-coding RNA GHRLOS and Its Prognostic
      Significance in Patients with Colorectal Cancer.
AB  - Long non-coding RNAs (lncRNAs), which have emerged as important regulatory RNA
      molecules that have been implicated in carcinogenesis and cancer progression, may
      also serve as novel potential biomarkers for cancer diagnosis and prognosis. Our
      previous analysis has identified the lncRNA GHRLOS, the ghrelin antisense strand
      non-coding RNA gene, as one of the hub genes in the co-expression network of
      differentially expressed lncRNAs/mRNAs in colorectal cancer (CRC). Here, we
      further evaluate the expression of GHRLOS in CRC and explore its clinical
      significance. The expression of GHRLOS in 366 pairs of CRC and adjacent non
      cancerous tissues was detected by quantitative RT-PCR assays. The results showed
      that the expression level of GHRLOS was significantly lower in CRC tissues than
      in matched non-cancerous tissues (P < 0.001). Decreased GHRLOS expression was
      observed in 54.4% (199/366) of cases, and was significantly correlated with the
      occurrence of lymph node metastasis (P = 0.033) and distant metastasis (P =
      0.005). A Kaplan-Meier analysis demonstrated that decreased GHRLOS expression
      contributed to poor disease-free survival (log-rank test, P < 0.001) and overall
      survival (log-rank test, P < 0.001). Moreover, a multivariate Cox regression
      analysis revealed the decreased expression of GHRLOS as an independent prognostic
      marker of poor outcomes [disease-free survival: hazard ratio (HR) = 2.02, 95%
      confidence interval (CI) = 1.42-3.88; overall survival: HR = 1.96, 95% CI = 1.34
      2.86] in CRC patients. In conclusion, our data suggest that the lncRNA GHRLOS
      might serve as a candidate biomarker of tumor metastasis and a prognostic
      indicator in CRC.

PMID- 29187881
TI  - Hazard rate of tumor recurrence over time in patients with colon cancer:
      implications for postoperative surveillance from three Japanese Foundation for
      Multidisciplinary Treatment of Cancer (JFMC) clinical trials.
AB  - Purpose: Reliable risk estimates of recurrence are necessary to establish optimal
      postoperative surveillance strategies. The purpose of the present study was to
      clarify changes in the hazard rate (HR) for tumor recurrence over time in
      Japanese patients with colon cancer. Methods: Data for 3984 patients from three
      clinical trials evaluating the benefit of adjuvant chemotherapy for colon cancer
      were analyzed. Estimated HRs were plotted over time for the entire cohort, as
      well as for node-positive and node-negative patients separately. The changes in
      risk were further analyzed according to eight clinical variables, and factors
      predictive of early (<3 years) and late (>3 years) recurrence were explored using
      Cox's regression analysis. Results: In node-positive patients, there was a
      prominent HR peak 0.6 years after surgery, whereas HR remained at consistently
      low levels in node-negative patients. In node-positive patients, HR decreased
      steadily until 3 years, after which the decline in HR plateaued. Those with T4
      tumors had a prominent HR peak around 1 year, including node-negative patients.
      The HR for T1/T2 Stage III colon cancers showed a similar pattern as that for T1
      T3 node-negative colon cancers. Cox regression analysis revealed that a lack of
      adjuvant chemotherapy, positive node status, T3/T4 factors, and male gender
      predict early recurrence, whereas patients with lymph node metastasis, T4 tumors,
      and a lesser extent of lymph node removal have a higher risk of recurrence 3-4
      years after surgery (P<0.05). Conclusion: The present study supports the concept
      of intensive surveillance during the first 3 years after curative resection.
      However, a reduction in surveillance intensity may be acceptable for patients
      with T3 Stage II and T1/T2 Stage III colon cancer.

PMID- 29187882
TI  - Proteomic analysis of lung metastases in a murine breast cancer model reveals
      divergent influence of CTSB and CTSL overexpression.
AB  - Studies in the MMTV-PyMT (PyMT) breast cancer mouse model have shown a strong
      influence of the lysosomal cysteine cathepsins B or L on lung metastasis
      formation. Transgenic expression of human CTSB (tgCTSB) or CTSL (tgCTSL) both led
      to similar metastatic phenotypes with increased metastatic burden in the PyMT
      mice. However, recent studies in other tumor models proved marked differences in
      effects of either cathepsin on the proteome composition. We sought to analyze and
      compare proteome changes in the metastatic proteome of PyMT mice expressing
      either tgCTSB or tgCTSL to evaluate similarities and differences in those models.
      Performing an explorative, quantitative proteome comparison based on LC-MS/MS, we
      identified up to 3,000 proteins from murine lung metastases in three independent
      biological replicates per genotype. In both cases, when compared to wild-type
      (WT) mice, we noticed a pronounced impact of transgene cathepsin expression on
      the metastasis proteome. Highlights include increased moesin, integrin beta 1 and
      vinexin levels in the tgCTSB dataset and increased saposin and granulin levels in
      the tgCTSL dataset. Importantly, non-supervised hierarchical clustering clearly
      separated tgCTSB vs. tgCTSL induced proteome changes. In summary, tgCTSB and
      tgCTSL both display a strong and distinct impact on proteome composition of lung
      macrometastases in the PyMT model. Our observations suggest that they impact
      malignant behavior in distinct ways, thus further emphasizing interest into their
      tumor-contextual functionality.

PMID- 29187884
TI  - A Single Nucleotide Polymorphism in HPGD Gene Is Associated with Prostate Cancer
      Risk.
AB  - Introduction: The HPGD gene was associated with some cancers, such as colorectal,
      breast, prostate, and bladder. However, detailed role of 15-hydroxyprostaglandin
      dehydrogenase (HPGD) gene remain unclear in prostate cancer. The study was to
      investigate the correlation between rs8752 that located in the 3'untranslated
      region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene and
      prostate cancer (PCa) risk. Materials and Methods: 109 patients from the First
      Affiliate Hospital of Soochow University were recruited. According to the results
      of pathologic diagnosis, all patients were divided into two groups (prostate
      cancer and benign prostatic hyperplasia). The single-nucleotide polymorphism
      (SNP) rs8752 was genotyped in all samples by direct sequencing. Results: 54
      prostate cancer and 55 BPH patients were included with a median age of 70.41 and
      67.62 years, respectively. No statistically significant difference between two
      groups in patient criteria. The frequency of the GG homozygote and AG+GG genotype
      were 37.74% and 62.26% in 54 prostate cancer samples, while in 55BPH patients,
      values were 62.50% and 37.50%. Compared with the GG genotype, the combined GA+AA
      genotypes had a significantly higher risk of prostate cancer (OR = 2.750; 95% CI:
      1.266-5.971, p = 0.011). Furthermore, the risk effect was obtained in subgroups
      of PCa patient group, the AA+AG genotypes significantly associated with the
      higher Gleason score samples (AA+AG vs GG: OR = 3.50, 95%CI = 1.106-11.072, p =
      0.033) and the risk of pathological stage (AA+AG vs GG: OR = 4.00, 95%CI = 1.253
      12.767, p = 0.019). Conclusions: rs8752 in the 3'untranslated region (UTR) of the
      15-hydroxyprostaglandin dehydrogenase (HPGD) gene was found to be responsible for
      the susceptibility to prostate cancer in Chinese individuals.

PMID- 29187883
TI  - Programmed cell death ligand 1 protein levels predicted survival of non-small
      cell lung cancer.
AB  - Objective: To investigate the relationship between programmed death ligand 1 (PD
      L1) expression using 5%, 25%, 50% cutoffs in tumor cells (TC) and postsurgical
      survival in non-small-cell lung cancer (NSCLC) patients. For samples with tumor
      infiltrating lymphocytes (TIL), correlation between PD-L1 expression in TIL using
      1% cutoff and postsurgical survival was also evaluated. Methods: Primary NSCLC
      tumor surgical samples staging I to IIIA of 126 patients who underwent surgical
      procedures from September 2009 to August 2012 in Shanghai Chest Hospital,
      Shanghai Jiao Tong University were retrospectively included. PD-L1 protein
      expression was detected by immunohistochemistry (IHC) assays. A rabbit anti-human
      PD-L1 (E1L3N) monoclonal antibody (1:300, CST#13684, Cell Signaling Technology)
      was used for PD-L1 IHC staining. PD-L1 expression was evaluated both on TC and
      TIL. Univariate and multivariate analyses for postsurgical survival were done
      using Kaplan-Meier and Cox regression model, respectively. Results: The median
      postsurgical survival for all patients was 44.1 months [95% confidence interval
      (CI): 33.9-70.0 months). The median postsurgical survival for PD-L1 expression
      percentage 0, 1-50% and >=50% were 51.9 months (95%CI: 33.9-70.0 months), 33.2
      months (95%CI: 20.8-45.6 months) and 14.7 months (95%CI: 1.9-27.6 months),
      respectively (P = 0.002). Clinical stage and PD-L1 expression in TC (25% cutoff
      or 50% cutoff values) were found to be independent predictors for longer
      postsurgical survival in all cohort. Ninety (71.4%) of the 126 samples were
      identified to concurrent TIL. The median postsurgical survival time was 39.6
      months (95% CI: 31.8-47.4 months) in patients with TIL. PD-L1 expression in TC
      (25% cutoff or 50% cutoff values) was found to be the independent predictor for
      longer postsurgical survival time in patients with TIL. Conclusion: PD-L1
      negative expression in TC at 25% or 50% cutoff values was the independent
      predictor for longer postsurgical survival time in both NSCLC samples and NSCLC
      samples with TIL. For patients with PD-L1 high expression at 25% or 50% cutoff
      values, PD-L1 blocking may be considered.

PMID- 29187885
TI  - Huaier Restrains Proliferative and Migratory Potential of Hepatocellular
      Carcinoma Cells Partially Through Decreased Yes-Associated Protein 1.
AB  - In China, Trametes robiniophila Murr (Huaier), a traditional Chinese herbal
      medicine, has been widely used in adjuvant therapies of hepatocellular carcinoma
      (HCC). However, the molecular mechanisms have not been fully understood. The aims
      of this study are to investigate the functions and mechanisms of Huaier on
      inhibiting proliferation and migration of HCC cells. Firstly, cell counting kit-8
      (CCK-8) and colony formation shown Huaier inhibited proliferation of HCC Bel
      7404, Bel-7402 and SMMC-7721 cells in a dose-dependent manner, and this
      inhibition might be due to Huaier decreased the expressions of the proliferating
      cell nuclear antigen (PCNA), the nuclear proliferation related antigen (Ki-67)
      and CyclinD1 detected by western blotting analysis. Notably, we also found Huaier
      treatment did not cause any cytotoxicity to normal human hepatocyte L-02 cells.
      Next, we found Huaier dose-dependently decreased Bcl-2 expression and increased
      Bax expression in Bel-7404 cells. The activities of cleaved caspase substrates
      had also been enhanced after Huaier treatment, suggesting Huaier treatment could
      induce HCC cell apoptosis. Then, the inhibitory effects of Huaier on migration of
      Bel-7404, Bel-7402 and SMMC-7721 cells via inhibiting Epithelial mesenchymal
      transition (EMT) had also been proved. Moreover, we confirmed yes-associated
      protein 1 (YAP1) was up-regulated in HCC cells and tissues, and overexpression of
      YAP1 promoted HCC cell proliferation and migration. Then, western blot and
      immunefluorescence shown Huaier had the inhibitory effects on YAP1 in HCC cells.
      On the other hand, human liver cancer tissue microarray (TMA) shown YAP1
      expression was closely to clinic. Our study also confirmed Huaier had the
      inhibitory effects on YAP1 in xenograft mice models, it could be because Huaier
      treatment translocated YAP1 from nucleus to cytoplasm, and further promoted
      phosphorylation of YAP1 to be degraded by ubiquitination. Hence, we conclude that
      Huaier may restrain the proliferation and migration of HCC cells via down
      regulation of YAP1. In summary, our study reveals the potential mechanisms of
      Huaier on inhibiting proliferation and migration of HCC cells. Importantly, for
      the first time, we found that Huaier can inhibit YAP1 expression in this anti
      tumor process. We believe this finding is beneficial for the clinical
      applications of Huaier and the targeted therapies for HCC.

PMID- 29187886
TI  - Prognostic value of tumor-infiltrating Foxp3+ regulatory T cells in patients with
      breast cancer: a meta-analysis.
AB  - PURPOSE: The prognostic value of tumor-infiltrating Foxp3+ regulatory T cells
      (Tregs) in breast cancer remains controversial. Therefore, we performed this meta
      analysis to determine the impact of Foxp3+ Tregs infiltration on survival
      outcomes. METHODS: Relevant literature was retrieved from Pubmed, Web of science
      and Cocohrane until May 30, 2016. Meta-analysis was performed using hazard ratios
      (HRs), odds ratio (OR) and 95 % confidence intervals (CI) as effect measures.
      RESULTS: Fourteen studies (10,259 patients) were included. Meta-analysis showed
      that high Foxp3+ Tregs infiltration was correlated with high histological grade
      (OR= 2.96, 95%CI [2.03-4.31]), estrogen receptor (ER) negativity (OR= 0.38, 95%CI
      [0.23-0.60]), human epidermal growth factor receptor type 2 (HER2) positivity
      (OR=2.43, 95%CI [1.69-3.51]). The detection of FOXP3+ Tregs was significantly
      associated with recurrence-free survival (RFS) of patients (HR = 1.58, 95 % CI
      [1.03-2.44]). CONCLUSION: Our meta-analysis suggests that high Foxp3+ Tregs
      infiltration is associated with poor RFS in breast cancer patients and predicts
      histological grade, estrogen receptor and HER-2 status.

PMID- 29187887
TI  - Long Non-coding RNA XIST Promotes Glioma Tumorigenicity and Angiogenesis by
      Acting as a Molecular Sponge of miR-429.
AB  - Glioma is a worldwide malignancy, which displays significantly active metastasis
      and angiogenesis. Interaction between long non-coding RNAs (lncRNAs) and
      microRNAs (miRNAs) has been shown to play crucial role in regulating tumor
      properties. However, the potential of lncRNA X-inactive specific transcript
      (XIST) to function as a miRNA regulator and its relevance in glioma
      tumorigenicity and angiogenesis have so far remained unclear. Expression analysis
      of lncRNA XIST in glioma cells revealed its significant up-regulation.
      Interestingly, silencing of XIST repressed both metastatic and pro-angiogenic
      ability in vitro as well as in vivo. Subsequent studies revealed that lncRNA XIST
      expression inversely correlated with miR-429 expression in glioma cells; miR-429
      modulated XIST expression by directly targeting the XIST gene sequence. In
      addition, miR-429 inhibitor restored metastatic and pro-angiogenic ability of
      gliomas abolished by silencing XIST. Our data provide insight into the key roles
      of the lncRNA-miRNA functional network in gliomas, which can aid in developing
      new therapeutic strategies for gliomas through clinical trials.

PMID- 29187888
TI  - Advantage of PET/CT in Target Delineation of MRI-negative Cervical Lymph Nodes In
      Intensity-Modulated Radiation Therapy Planning for Nasopharyngeal Carcinoma.
AB  - Introduction: In intensity-modulated radiation therapy (IMRT) planning for
      nasopharyngeal carcinoma (NPC), cervical lymph nodes (CLNs) that appear negative
      on magnetic resonance imaging (MRI) scans can be difficult to target. The purpose
      of this study was to assess the advantage of 18F-fluorodeoxyglucose positron
      emission tomography with computed tomography (18F-FDG PET/CT) for distinguishing
      MRI-negative CLNs and the effect of 18F-FDG PET/CT on diagnosis, target
      delineation, and dose prescription in IMRT planning for NPC. Methods: Thirty-five
      NPC patients with 37 MRI-negative CLNs underwent 18F-FDG PET/CT imaging before
      treatment. Ultrasonography-guided fine-needle aspiration cytology (USgFNAC) was
      performed to examine the pathology of CLNs. The 18F-FDG PET/CT and
      cytopathological results were compared, and the diagnostic accuracy of 18F-FDG
      PET/CT was calculated. The cytopathologically confirmed CLNs were delineated and
      treated as the gross tumor volume of lymph nodes (denoted as GTVnd). Results:
      Nineteen of the 37 MRI-negative CLNs were positive on 18F-FDG PET/CT, and
      metastasis was confirmed by USgFNAC in 16 CLNs. Of the remaining 18 18F-FDG
      PET/CT-negative lymph nodes, metastasis was confirmed in one. The diagnostic
      accuracy, sensitivity, and specificity of 18F-FDG PET/CT were 89.2%, 94.1%, and
      85.0%, respectively. The positive and negative predictive values were 84.2% and
      94.4%, respectively. With a median follow-up of 48.3 months, no relapse was
      observed among the 18F-FDG PET/CT-positive CLNs with metastasis confirmed by
      USgFNAC and treated as GTVnd. Conclusion:18F-FDG PET/CT had high accuracy,
      sensitivity, and specificity for distinguishing MRI-negative CLNs. 18F-FDG PET/CT
      positive CLNs could reasonably be categorized as high-risk clinical tumor volume
      in IMRT planning for NPC.

PMID- 29187889
TI  - T-cell Acute Lymphoblastic Leukemia Cells Display Activation of Different
      Survival Pathways.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is a disease of the blood affecting T
      lymphocytes. Although notable improvements have been achieved in T-ALL treatment,
      half of the adult T-ALL patients still experience treatment failure. In order to
      develop a targeted therapy, we need a better understanding of T-ALL pathogenesis.
      In this study, we used patient-derived cell lines which display resistance to
      glucocorticoids. We observed that different cell lines are dependent on different
      survival signaling pathways. Aberrant activation of AKT, p38, S6K or ERK
      signaling was not found to the same degree in all cell lines studied. To
      understand the molecular differences in T-ALL cells, we compared gene expression
      and somatic mutations. Gene set enrichment analysis showed enrichment of the
      mTORC1, MAPK or TGF-beta signaling pathways. Loss-of-function mutations in the
      TP53 and FBXW7 genes were identified in all cell lines investigated. Thus, we
      suggest that T-ALL cells from different patients are addicted to different
      mutations and thereby to different signaling pathways. Therefore, understanding
      the enrichment of molecular pathways for each individual patient will provide us
      with a more precise and specific treatment plan.

PMID- 29187890
TI  - Decreased KPNB1 Expression is Induced by PLK1 Inhibition and Leads to Apoptosis
      in Lung Adenocarcinoma.
AB  - Lung cancer is a major cause of death worldwide, with lung adenocarcinoma being
      the most frequently diagnosed subtype in Japan. Finding the target of an
      anticancer drug can improve lung adenocarcinoma treatments. Polo-like kinase 1
      (PLK1) is an essential mitotic kinase in mitotic progression, and PLK1 inhibition
      induces cell cycle arrest and apoptosis in tumor cells. In addition, a variety of
      PLK1 inhibitors have been identified for cancer treatments. In this study, we
      looked for the target gene of the anticancer drug that has synergy with PLK1
      inhibitors. We identified karyopherin beta 1 (KPNB1) as a possible target for
      lung adenocarcinoma treatment. We found that PLK1 inhibition decreased KPNB1
      expression in lung adenocarcinoma cells and KPNB1 depletion inhibited cell
      proliferation via apoptosis. The same apoptosis signaling pathway may be
      activated because the expression of common apoptosis-related genes was decreased
      by PLK1 and KPNB1 silencing; however, the time course of cell growth inhibition
      was somewhat different. Cell cycle analysis showed that KPNB1 depletion increased
      the proportion of cells at the G0/G1 phase, although cells also accumulated at
      the G2/M phase in PLK1-depleted cells. Our findings suggest that decreased KPNB1
      expression may be associated with the apoptosis induced by PLK1 inhibition.

PMID- 29187892
TI  - Defining Radiation-Induced Hepatic Toxicity in Hepatocellular Carcinoma Patients
      Treated with Stereotactic Body Radiotherapy.
AB  - The definition and criteria of radiation-induced hepatic toxicity (RIHT) in
      hepatocellular carcinoma patients vary among studies. Therefore, the reported
      rates of RIHT differ among studies, and this causes confusion. In this study, we
      evaluated RIHT using several laboratory and clinical parameters, and analyzed
      which criterion is more correlated with RT and survival. Forty-five HCC patients
      treated with stereotactic body radiotherapy were included for the analysis. All
      patients had unresectable HCC and Child-Pugh (CP) class A or B baseline liver
      function. A median total dose of 45 Gy was delivered by CyberKnife in 3
      fractions. For individual laboratory parameter, >= grade 2 toxicity development
      of bilirubin, albumin, or prothrombin time by Common Terminology Criteria of
      Adverse Effects (CTCAE) was correlated with mean liver dose and survival.
      However, serum transaminases had no correlation with liver mean dose and
      survival, and were rather affected by other local treatments. Compared to the
      CTCAE, the increase in the CP score of 2 points or more was better correlated
      with liver failure and overall survival, and it was not affected by other local
      treatments or tumor progression. We concluded RIHT was better defined by the
      change in the CP score rather than the CTCAE in patients treated by stereotactic
      body radiotherapy for HCC.

PMID- 29187893
TI  - Detection of Treatment Success after Photodynamic Therapy Using Dynamic Contrast
      Enhanced Magnetic Resonance Imaging.
AB  - Early evaluation of response to therapy is crucial for selecting the optimal
      therapeutic follow-up strategy for cancer patients. PDT is a photochemistry-based
      treatment modality that induces tumor tissue damage by cytotoxic oxygen radicals,
      generated by a pre-injected photosensitive drug upon light irradiation of tumor
      tissue. Vascular shutdown is an important mechanism of tumor destruction for most
      PDT protocols. In this study, we assessed the suitability of Dynamic Contrast
      Enhanced Magnetic Resonance Imaging (DCE-MRI) to evaluate treatment efficacy
      within a day after photodynamic therapy (PDT), using the tumor vascular response
      as a biomarker for treatment success. Methods: DCE-MRI at 7 T was used to measure
      the micro-vascular status of subcutaneous colon carcinoma tumors before, right
      after, and 24 h after PDT in mice. Maps of the area under the curve (AUC) of the
      contrast agent concentration were calculated from the DCE-MRI data. Besides,
      tracer kinetic parameters including Ktrans were calculated using the standard
      Tofts-Kermode model. Viability of tumor tissue at 24 h after PDT was assessed by
      histological analysis. Results: PDT led to drastic decreases in AUC and Ktrans or
      complete loss of enhancement immediately after treatment, indicating a vascular
      shutdown in treated tumor regions. Histological analysis demonstrated that the
      treatment induced extensive necrosis in the tumors. For PDT-treated tumors, the
      viable tumor fraction showed a strong correlation (rho >= 0.85) with the tumor
      fraction with Ktrans > 0.05 min-1 right after PDT. The viable tumor fraction also
      correlated strongly with the enhanced fraction, the average Ktrans , and the
      fraction with Ktrans > 0.05 min-1 at 24 h after PDT. Images of the viability
      stained tumor sections were registered to the DCE-MRI data, demonstrating a good
      spatial agreement between regions with Ktrans > 0.05 min-1 and viable tissue
      regions. Finally, 3D post-treatment viability detection maps were constructed for
      the tumors of three mice by applying a threshold (0.05 min-1) to Ktrans at 24 h
      after PDT. As a proof of principle, these maps were compared to actual tumor
      progression after one week. Complete tumor response was correctly assessed in one
      animal, while residual viable tumor tissue was detected in the other two at the
      locations where residual tumor tissue was observed after one week. Conclusion:
      This study demonstrates that DCE-MRI is an effective tool for early evaluation of
      PDT tumor treatment.

PMID- 29187891
TI  - Post-transcriptional Regulation of Genes Related to Biological Behaviors of
      Gastric Cancer by Long Noncoding RNAs and MicroRNAs.
AB  - Noncoding RNAs play critical roles in regulating protein-coding genes and
      comprise two major classes: long noncoding RNAs (lncRNAs) and microRNAs (miRNAs).
      LncRNAs regulate gene expression at transcriptional, post-transcriptional, and
      epigenetic levels via multiple action modes. LncRNAs can also function as
      endogenous competitive RNAs for miRNAs and indirectly regulate gene expression
      post-transcriptionally. By binding to the 3'-untranslated regions (3'-UTR) of
      target genes, miRNAs post-transcriptionally regulate gene expression. Herein, we
      conducted a review of post-transcriptional regulation by lncRNAs and miRNAs of
      genes associated with biological behaviors of gastric cancer.

PMID- 29187894
TI  - Material-induced Senescence (MIS): Fluidity Induces Senescent Type Cell Death of
      Lung Cancer Cells via Insulin-Like Growth Factor Binding Protein 5.
AB  - Objective: We propose here material-induced senescence (MIS) as a new therapeutic
      concept that limits cancer progression by stable cell cycle arrest. This study
      examined for the first time the effect of material fluidity on cellular
      senescence in lung carcinoma using poly(epsilon-caprolactone-co-D, L-lactide)
      (P(CL-co-DLLA)) with tunable elasticity and fluidity. Methods: The fluidity was
      varied by chemically crosslinking the polymer networks: the crosslinked P(CL-co
      DLLA) shows solid-like properties with a stiffness of 260 kPa, while the non
      crosslinked polymer exists in a quasi-liquid state with loss and storage moduli
      of 33 kPa and 11 kPa, respectively. Results: We found that cancer cells growing
      on the non-crosslinked, fluidic substrate undergo a non-apoptotic form of cell
      death and the cell cycle was accumulated in a G0/G1 phase. Next, we investigated
      the expression of biomarkers that are associated with cancer pathways. The cancer
      cells on the fluidic substrate expressed several biomarkers associated with
      senescence such as insulin-like growth factor binding protein 5 (IGFBP5). This
      result indicates that when cancer cells sense fluidity in their surroundings, the
      cells express IGFBP5, which in turn triggers the expression of tumor suppressor
      protein 53 and initiates cell cycle arrest at the G1 phase followed by cellular
      senescence. Furthermore, the cancer cells on the fluidic substrate maintained
      their epithelial phenotype, suggesting that the cancer cells do not undergo
      epithelial to mesenchymal transition. Conclusion: By considering these results as
      the fundamental information for MIS, our system could be applied to induce
      senescence in treatment-resistant cancers such as metastatic cancer or cancer
      stem cells.

PMID- 29187895
TI  - Follicular Stimulating Hormone Accelerates Atherogenesis by Increasing
      Endothelial VCAM-1 Expression.
AB  - Rationale: Postmenopausal atherosclerosis (AS) has for decades been attributed to
      estrogen deficiency. Although the follicular stimulating hormone (FSH) levels
      rise sharply in parallel, the direct effect of FSH on AS has never been
      investigated. In this study, we explored the possible role of FSH in the
      development of AS. Methods: This was a prospective cohort study of 48 healthy
      premenopausal and 15 postmenopausal women. ApoE knockout mice were used as
      atherosclerosis model and human umbilical vascular endothelial cells (HUVECs)
      were cultured as cell model. Serum hormones and vascular cell adhesion molecule-1
      (VCAM-1) levels were measured. Real-time PCR, histology for atherosclerotic
      lesions, immunofluorescence, luciferase assay, transfection experiments, flow
      chamber adhesion assay and western blot were performed. Results: In ApoE knockout
      mice, administration of FSH increased the atherosclerotic lesions and serum VCAM
      1 concentration. Importantly, in blood samples of postmenopausal women, we
      detected significantly higher levels of FSH and VCAM-1 compared with those from
      premenopausal women, and there was a positive correlation between these two
      molecules. In cultured HUVECs, FSH receptor (FSHR) mRNA and protein expression
      were detected and FSH enhanced VCAM-1 expression. This effect was mediated by the
      activation of nuclear factor kappaB (NF-kappaB), which was sequentially enhanced
      by the activation of PI3K/Akt/mTOR cascade. FSH first enhanced GalphaS activity
      resulting in elevated cAMP level and PKA activity, which relayed the signals from
      FSHR to the PI3K/Akt/mTOR cascade. Furthermore, FSHR was detected in endothelial
      caveolae fraction and interacted with caveolin-1 and GalphaS. The disruption of
      caveolae or the silencing of caveolin-1 blocked FSH effects on signaling
      activation and VCAM-1 expression, suggesting the existence of a functional
      signaling module in membrane caveolae. Finally, FSH increased human monocyte
      adhesion to HUVECs which was reversed by the VCAM-1 neutralizing antibody.
      Conclusion: FSHR was located in the membrane caveolae of HUVECs and FSH promoted
      VCAM-1 expression via FSHR/GalphaS /cAMP/PKA and PI3K/Akt/mTOR/NF-kappaB pathway.
      This may contribute to the deleterious role of FSH in the development of AS in
      postmenopausal women.

PMID- 29187896
TI  - CO2-based amphiphilic polycarbonate micelles enable a reliable and efficient
      platform for tumor imaging.
AB  - : Biodegradable polymeric nanomaterials can be directly broken down by
      intracellular processes, offering a desirable way to solve toxicity issues for
      cancer diagnosis and treatment. Among them, aliphatic polycarbonates are approved
      for application in biological fields by the United States Food and Drug
      Administration (FDA), however, high hydrophobicity, deficient functionality and
      improper degradation offer significant room for improvement in these materials.
      METHODS: To achieve progress in this direction, herein, we demonstrate that CO2
      based amphiphilic polycarbonates (APC) with improved hydrophilicity and
      processability can be used as a reliable and efficient platform for tumor
      imaging. To better investigate their potential, we devised a convenient strategy
      through conjugation of APC with gadolinium (Gd). RESULTS: The resulting polymeric
      micelles (APC-DTPA/Gd) exhibit excellent magnetic resonance imaging performance,
      simultaneously enabling real-time visualization of bioaccumulation and
      decomposition of polymeric micelles in vivo. Importantly, these micelles can be
      degraded to renally cleared products within a reasonable timescale without
      evidence of toxicity. CONCLUSION: Our findings may help the development of CO2
      based amphiphilic polycarbonate for cancer diagnosis and treatment, accompanied
      by their low-toxicity degradation pathway.

PMID- 29187897
TI  - Glycan and Peptide IgE Epitopes of the TNF-alpha Blockers Infliximab and
      Adalimumab - Precision Diagnostics by Cross-Reactivity Immune Profiling of
      Patient Sera.
AB  - : Biological drugs like therapeutic antibodies are widely used for the treatment
      of various diseases like inflammatory disorders and cancer. A drawback of these
      novel treatments is the substantial proportion of patients experiencing adverse
      reactions such as loss-of-drug effect or hypersensitivity reactions. These
      reactions are associated with pre-existing and/or developing anti-drug
      antibodies. Especially IgE development is a risk factor for life-threatening
      systemic anaphylaxis. METHODS: In order to characterize the individual drug
      specific serum IgE, an IgE cross-reactivity immune profiling (ICRIP) assay was
      developed. Individual IgG epitopes of anti-drug antibodies against adalimumab
      were identified by epitope mapping via peptide microarray. RESULTS: ICRIP
      analyses of sera from patients treated with the therapeutic antibodies adalimumab
      (ADL) and infliximab (IFX) reveal individual, distinct IgE binding patterns. IgG
      epitopes were identified mostly located in the variable region of ADL.
      CONCLUSIONS: Using ICRIP and peptide microarrays for pharmacovigilance of the TNF
      alpha blockers IFX and ADL, risk factors and biomarkers before and during therapy
      shall be identified. These diagnostic systems provide the basis for a safe and
      efficacious therapy decision for each patient in cases of adverse drug reactions
      mediated by different types of anti-drug antibodies.

PMID- 29187898
TI  - Precisely Enumerating Circulating Tumor Cells Utilizing a Multi-Functional
      Microfluidic Chip and Unique Image Interpretation Algorithm.
AB  - Enumerating circulating tumor cells (CTCs) has been demonstrably useful in cancer
      treatment. Although there are several approaches that have proved effective in
      isolating CTC-like cells, the crucial identification of CTCs continues to rely on
      the manual interpretation of immunofluorescence images of all cells that have
      been isolated. This procedure is time consuming and more importantly, CTC
      identification relies on subjective criteria that may differ between examiners.
      In this study, we describe the design, testing, and verification of a
      microfluidic platform that provides accurate and automated CTC enumeration using
      a common objective criterion. Methods: The platform consists of a multi
      functional microfluidic chip and a unique image processing algorithm. The
      microfluidic chip integrates blood filtering, cell isolation, and single cell
      positioning to ensure minimal cell loss, efficient cell isolation, and fixed
      arraying of single cells to facilitate downstream image processing. By taking
      advantage of the microfluidic chip design to reduce calculation loads and
      eliminate measurement errors, our specially designed algorithm has the capability
      of rapidly interpreting hundreds of images to provide accurate CTC counts.
      Results: Following intensive optimization of the microfluidic chip, the image
      processing algorithm, and their collaboration, we verified the complete platform
      by enumerating CTCs from six clinical blood samples of patients with breast
      cancer. Compared to tube-based CTC isolation and manual CTC identification, our
      platform had better accuracy and reduced the time needed from sample loading to
      result review by 50%. Conclusion: This automated CTC enumeration platform
      demonstrates not only a sound strategy in integrating a specially designed multi
      functional microfluidic chip with a unique image processing algorithm for robust,
      accurate, and "hands-free" CTC enumeration, but may also lead to its use as a
      novel in vitro diagnostic device used in clinics and laboratories as readily as a
      routine blood test.

PMID- 29187899
TI  - Optimizing fresh specimen staining for rapid identification of tumor biomarkers
      during surgery.
AB  - RATIONALE: Positive margin status due to incomplete removal of tumor tissue
      during breast conserving surgery (BCS) is a prevalent diagnosis usually requiring
      a second surgical procedure. These follow-up procedures increase the risk of
      morbidity and delay the use of adjuvant therapy; thus, significant efforts are
      underway to develop new intraoperative strategies for margin assessment to
      eliminate re-excision procedures. One strategy under development uses topical
      application of dual probe staining and a fluorescence imaging strategy termed
      dual probe difference specimen imaging (DDSI). DDSI uses a receptor-targeted
      fluorescent probe and an untargeted, spectrally-distinct fluorescent companion
      imaging agent topically applied to fresh resected specimens, where the
      fluorescence from each probe is imaged and a normalized difference image is
      computed to identify tumor-target distribution in the specimen margins. While
      previous reports suggested this approach is a promising new tool for surgical
      guidance, advancing the approach into the clinic requires methodical protocol
      optimization and further validation. METHODS: In the present study, we used
      breast cancer xenografts and receiver operator characteristic (ROC) curve
      analysis to evaluate a wide range of staining and imaging parameters, and
      completed a prospective validation study on multiple tumor phenotypes with
      different target expression. Imaging fluorophore-probe pair, concentration, and
      incubation times were systematically optimized using n=6 tissue specimen
      replicates per staining condition. Resulting tumor vs. normal adipose tissue
      diagnostic performance were reported and staining patterns were validated via
      receptor specific immunohistochemistry colocalization. Optimal staining
      conditions were tested in receptor positive and receptor negative cohorts to
      confirm specificity. RESULTS: The optimal staining conditions were found to be a
      one minute stain in a 200 nM probe solution (area under the curve (AUC) = 0.97),
      where the choice of fluorescent label combination did not significantly affect
      the diagnostic performance. Using an optimal threshold value determined from ROC
      curve analysis on a training data set, a prospective study on xenografts resulted
      in an AUC=0.95 for receptor positive tumors and an AUC = 0.50 for receptor
      negative (control) tumors, confirming the diagnostic performance of this novel
      imaging technique. CONCLUSIONS: DDSI provides a robust, molecularly specific
      imaging methodology for identifying tumor tissue over benign mammary adipose
      tissue. Using a dual probe imaging strategy, nonspecific accumulation of targeted
      probe was corrected for and tumor vs. normal tissue diagnostic potential was
      improved, circumventing difficulties with ex vivo tissue specimen staining and
      allowing for rapid clinical translation of this promising technology for tumor
      margin detection during BCS procedures.

PMID- 29187900
TI  - The cytotoxic effects of dimethyl sulfoxide in mouse preimplantation embryos: a
      mechanistic study.
AB  - Rationale: Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water
      insoluble substances, a vehicle for drug therapy, and a cryoprotectant for
      cultured cells. DMSO induced embryonic defects and its mechanism of action
      remains unclear. The rationale is based on the assumption that DMSO
      supplementation should induce long-term negative effects on both pre- and post
      implantation embryo development. Methods: DMSO induced oxidative stress, ER
      stress, autophagy, mitophagy, signaling responsible genes and proteins were
      determined by RT-qPCR, Western blotting, immunofluorescence, and confocal
      microscopy. DMSO induced mitochondrial dysfunction was measured by transmission
      electron microcopy and JC-1 assay. Apoptosis was estimated using TUNEL and comet
      assay. Post-implantation embryo developmental capability was estimated by
      implantation site and fetus numbers. Results: Exposure to DMSO induced an early
      oxidative stress response within 0.5 to 2 h in 1-cell zygotes by disrupting the
      balance of pro- and anti-oxidants. Notably, DMSO-treated 2-cell embryos showed
      increased expression of unfolded protein response genes such as Hspa5, Hsp90b1,
      Ddit3, Atf4, and Xbp1. As a result, the development of many embryos is arrested
      at the 2-cell, 4-cell, or morula stages in a dose-dependent manner. Further, DMSO
      induced endoplasmic reticulum stress increased mitochondrial Ca2+ levels, induced
      mitochondrial depolarization/dysfunction, and induced apoptotic cell death via
      the JNK/ATF2-dependent pathway. Consequently, treatment with DMSO increased the
      expression of autophagy initiation-, phagophore elongation-, and autophagosome
      formation-related genes, as well as localization of PINK1/Parkin, which are the
      main mediators of mitophagy, in mitochondria. Interestingly, DMSO causes
      cytotoxic effects in preimplantation embryos by inducing extensive mitophagy and
      autophagy. Especially, DMSO treatment decreased the inner cell mass and
      trophectoderm cell numbers as well as mRNA expression of B3gnt5 and Wnt3a in
      developed blastocysts, which decreased the implantation and developmental rates
      of full-term offspring after being transferred into pseudopregnant mice.
      Conclusion: These results provide a significant contribution to finding effective
      protective agents to combat DMSO mediated reproductive toxicity for application
      in human embryos in the near future.

PMID- 29187902
TI  - Copper Manganese Sulfide Nanoplates: A New Two-Dimensional Theranostic
      Nanoplatform for MRI/MSOT Dual-Modal Imaging-Guided Photothermal Therapy in the
      Second Near-Infrared Window.
AB  - Multifunctional nanoplatforms with integrated diagnostic and therapeutic
      functions have attracted tremendous attention. Especially, the second near
      infrared (NIR-II) light response-based nanoplatforms hold great potential in
      cancer theranostic applications, which is because the NIR-II window provides
      larger tissue penetration depth and higher maximum permissible exposure (MPE)
      than that of the well-studied first near-infrared (NIR-I) window. Herein, we for
      the first time present a two-dimensional (2D)-nanoplatform based on Cu2MnS2
      nanoplates (NPs) for magnetic resonance imaging (MRI)/multispectral optoacoustic
      tomography (MSOT) dual-modal imaging-guided photothermal therapy (PTT) of cancer
      in the NIR-II window. Methods: Cu2MnS2 NPs were synthesized through a facile and
      environmentally friendly process. A series of experiments, including the
      characterization of Cu2MnS2 NPs, the long-term toxicity of Cu2MnS2 NPs in BALB/c
      nude mice, the applications of Cu2MnS2 NPs for in vitro and in vivo MRI/MSOT dual
      modal imaging and NIR-II PTT of cancer were carried out. Results: The as
      synthesized Cu2MnS2 NPs exhibit low cytotoxicity, excellent biocompatibility as
      well as high photothermal conversion efficiency (~49.38%) and outstanding
      photostability. Together with their good T1-shortening effect and strong
      absorbance in the NIR-I and NIR-II region, the Cu2MnS2 NPs display high-contrast
      imaging performance both in MRI and MSOT (900 nm laser source). Moreover, the
      subsequent in vitro and in vivo results demonstrate that the Cu2MnS2 NPs possess
      excellent PTT efficacy under 1064 nm laser irradiation with a low power density
      (0.6 W cm-2). In addition, the detailed long-term toxicity studies further
      confirming the safety of Cu2MnS2 NPs in vivo. Conclusion: We have developed a new
      2D Cu2MnS2 NPs as multifunctional theranostic agents for MRI/MSOT dual-modal
      imaging-guided PTT of cancer in the NIR-II window. Such biocompatible Cu2MnS2 NPs
      might provide a new perspective for exploring new 2D-based nanoplatforms with
      improved properties for clinical applications in the future.

PMID- 29187901
TI  - Mutational Landscape of cfDNA Identifies Distinct Molecular Features Associated
      With Therapeutic Response to First-Line Platinum-Based Doublet Chemotherapy in
      Patients with Advanced NSCLC.
AB  - Rationale To investigate whether the mutational landscape of circulating cell
      free DNA (cfDNA) could predict and dynamically monitor the response to first-line
      platinum-based chemotherapy in patients with advanced non-small-cell lung cancer
      (NSCLC). Methods Eligible patients were included and blood samples were collected
      from a phase III trial. Both cfDNA fragments and fragmented genomic DNA were
      extracted for enrichment in a 1.15M size panel covering exon regions of 1,086
      genes. Molecular mutational burden (MMB) was calculated to investigate the
      relationship between molecular features of cfDNA and response to chemotherapy.
      Results In total, 52 eligible cases were enrolled and their blood samples were
      prospectively collected at baseline, every cycle of chemotherapy and time of
      disease progression. At baseline, alterations of 17 genes were found. Patients
      with partial response (PR) had significantly lower baseline MMB of these genes
      than those patients with either stable disease (SD) (P = 0.0006) or progression
      disease (PD) (P = 0.0074). Further analysis revealed that the mutational
      landscape of cfDNA from pretreatment blood samples were distinctly different
      among patients with PR vs. SD/PD. For patients with baseline TP53 mutation, those
      with PR experienced a significant reduction in MMB whereas patients with SD or PD
      experienced an increase after two, three or four cycles of chemotherapy.
      Furthermore, patients with low MMB had superior response rate and significantly
      longer progression-free survival than those with high MMB. Conclusion This study
      indicated that the mutational landscape of cfDNA has potential clinical value to
      predict the therapeutic response to first-line platinum-based doublet
      chemotherapy in NSCLC patients. At the single gene level, dynamic change of
      molecular mutational burden of TP53 is valuable to monitor efficacy (and,
      therefore, might aid in early recognition of resistance and relapse) in patients
      harboring this mutation at baseline.

PMID- 29187903
TI  - miR34a/GOLPH3 Axis abrogates Urothelial Bladder Cancer Chemoresistance via
      Reduced Cancer Stemness.
AB  - Rationale: Chemoresistance and subsequent recurrence of human urothelial bladder
      cancer (UBC) is partially driven by a subpopulation of tumor initiating cells,
      namely cancer stem cells (CSCs). However, the underlying molecular mechanism in
      chemotherapy-induced CSCs enrichment and following chemoresistance and recurrence
      remains largely unclear. Methods: Gemcitabine and cisplatin (GC) chemoresistant
      cell lines (T24 GC 3rd and 5637 GC 3rd cells) and the chemo-sensitive UBC cell
      lines T24 and 5637 were established in vivo for the investigation of acquired
      resistance mechanisms. The role of miR34a/GOLPH3 axis in regulating UBC
      chemoresistance and recurrence was evaluated in cell and animal models. The
      expression levels of miR34a/GOLPH3 axis and CSCs markers were assayed in
      specimens of UBC. The association of GOLPH3 with clinicopathologic features and
      prognosis was analysed. Results: RT-PCR and western blotting confirmed that the
      expression levels of miR34a were decreased and GOLPH3 were increased in GC
      chemoresistant UBC cell lines. Downregulation of miR34a resulted in the
      overexpression of GOLPH3, which is a target gene of miR34a confirmed by
      luciferase experiment. The ectopic expression of miR34a decreased the stem cell
      properties of chemoresistant UBC cells and re-sensitized these cells to GC
      treatment in vitro and in vivo. Moreover, miR34a/GOLPH3 axis has obvious clinical
      relevance with prognosis and recurrence in human UBC patients with standard GC
      chemotherapy. Conclusion: Our results suggest that miR34a/GOLPH3 axis exert key
      role in CSCs involved UBC drug resistance and recurrence and warrant further
      development as a promising therapeutic approach in treating drug-resistant UBC.

PMID- 29187904
TI  - Multimodality Imaging of Angiogenesis in a Rabbit Atherosclerotic Model by GEBP11
      Peptide Targeted Nanoparticles.
AB  - Background and Aims: Angiogenesis is an important pathological process during
      progression of plaque formation, which can result in plaque hemorrhage and
      vulnerability. This study aims to explore non-invasive imaging of angiogenesis in
      atherosclerotic plaque through magnetic resonance imaging (MRI) and positron
      emission tomography (PET) by using GEBP11 peptide targeted magnetic iron oxide
      nanoparticles in a rabbit model of atherosclerosis. Methods: The dual-modality
      imaging probe was constructed by coupling 2, 3-dimercaptosuccinnic acid-coated
      paramagnetic nanoparticles (DMSA-MNPs) and the PET 68Ga chelator 1,4,7
      triazacyclononane-N, N', N''-triacetic acid (NOTA) to GEBP11 peptide. The
      atherosclerosis model was induced in New Zealand white rabbits by abdominal aorta
      balloon de-endothelialization and atherogenic diet for 12 weeks. The plaque areas
      in abdominal artery were detected by ultrasound imaging and Oil Red O staining.
      Immunofluorescence staining and Prussian blue staining were applied respectively
      to investigate the affinity of GEBP11 peptide. MTT and flow cytometric analysis
      were performed to detect the effects of NGD-MNPs on cell proliferation, cell
      cycle and apoptosis in Human umbilical vein endothelial cells (HUVECs). In vivo
      MRI and PET imaging of atherosclerotic plaque were carried out at different time
      points after intravenous injection of nanoparticles. Results: The NGD-MNPs with
      hydrodynamic diameter of 130.8 nm +/- 7.1 nm exhibited good imaging properties,
      high stability, low immunogenicity and little cytotoxicity. In vivo PET/MR
      imaging revealed that 68Ga-NGD-MNPs were successfully applied to visualize
      atherosclerotic plaque angiogenesis in the rabbit abdominal aorta. Prussian blue
      and CD31 immunohistochemical staining confirmed that NGD-MNPs were well co
      localized within the blood vessels' plaques. Conclusion:68Ga-NGD-MNPs might be a
      promising MR and PET dual imaging probe for visualizing the vulnerable plaques.

PMID- 29187905
TI  - Nanoparticle Delivery of miR-34a Eradicates Long-term-cultured Breast Cancer Stem
      Cells via Targeting C22ORF28 Directly.
AB  - Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of
      therapeutic resistance and metastasis, due to their unique abilities of self
      renew, wide differentiation potentials and resistance to most conventional
      therapies. It is a proactive strategy for cancer therapy to eradicate CSCs.
      Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were
      isolated by fluorescence-activated cell sorting (FACS); while cell line-derived
      BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated
      cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were
      performed in multiple breast cell lines. The mentioned nanoparticles were
      constructed following the standard molecular cloning protocol. Tissue microarray
      analysis has been used to study 217 cases of clinical breast cancer specimens.
      Results: Here, we have successfully established four long-term maintenance BCSC
      that retain their tumor-initiating biological properties. Our analyses of
      microarray and qRT-PCR explored that miR-34a is the most pronounced microRNA for
      investigation of BCSC. We establish hTERT promoter-driven VISA delivery of miR
      34a (TV-miR-34a) plasmid that can induce high throughput of miR-34a expression in
      BCSC. TV-miR-34a significantly inhibited the tumor-initiating properties of long
      term-cultured BCSC in vitro and reduced the proliferation of BCSC in vivo by an
      efficient and safe way. TV-miR-34a synergizes with docetaxel, a standard therapy
      for invasive breast cancer, to act as a BCSC inhibitor. Further mechanistic
      investigation indicates that TV-miR-34a directly prevents C22ORF28 accumulation,
      which abrogates clonogenicity and tumor growth and correlates with low miR-34 and
      high C22ORF28 levels in breast cancer patients. Conclusion: Taken together, we
      generated four long-term maintenance BCSC derived from either clinical specimens
      or cell lines, which would be greatly beneficial to the research progress in
      breast cancer patients. We further developed the non-viral TV-miR-34a plasmid,
      which has a great potential to be applied as a clinical application for breast
      cancer therapy.

PMID- 29187906
TI  - The Changing Therapeutic Role of Chemo-radiotherapy for Loco-regionally Advanced
      Nasopharyngeal Carcinoma from Two/Three-Dimensional Radiotherapy to Intensity
      Modulated Radiotherapy: A Network Meta-Analysis.
AB  - Purpose: We used randomized trials of radiotherapy (RT) with or without
      chemotherapy in non-metastatic nasopharyngeal carcinoma to investigate the
      survival benefit of chemoradiotherapy regimens between two/three-dimensional
      radiotherapy (2D/3D RT) and intensity-modulated radiotherapy (IMRT). Methods:
      Overall, 27 trials and 7,940 patients were included. Treatments were grouped into
      seven categories including RT alone, induction chemotherapy (IC) followed by RT
      (IC-RT), RT followed by adjuvant chemotherapy (RT-AC), IC followed by RT followed
      by AC (IC-RT-AC), concurrent chemo-radiotherapy (CRT), IC followed by CRT (IC
      CRT), and CRT followed by AC (CRT-AC). To distinguish between 2D/3D RT and IMRT,
      three categories in IMRT were newly added, including CRT in IMRT, IC-CRT in IMRT,
      and CRT-AC in IMRT. The P score was used to rank the treatments. Results: Both
      fixed- and random-effects frequentist and Bayesian network meta-analysis models
      were applied, which provided similar results and the same ranking. IC-CRT was the
      most effective regimen compared with CRT-AC and CRT in the IMRT era for overall
      survival (OS) (HR, 95% CI, IC-CRT vs. CRT-AC, 0.61 (0.45, 0.82); IC-CRT vs. CRT
      0.65 (0.47, 0.91)), progression-free survival (PFS) (0.69 (0.54, 0.88); 0.63
      (0.49, 0.80)), and distant metastasis-free survival (DMFS) (0.58 (0.28, 1.21);
      0.60 (0.42, 0.85)). CRT-AC achieved the highest survival benefit compared with
      CRT, and IC-CRT for loco-regional relapse-free survival (LRRFS) (0.44 (0.15,
      1.28); 0.72 (0.22, 2.33)). Among these 10 categories, after distinguishing
      between 2D/3D RT and IMRT, IC-CRT in IMRT ranked first for OS, PFS, and DMFS, and
      CRT-AC in IMRT ranked first for LRRFS. Conclusion: IC-CRT should be the most
      suitable regimen for loco-regionally advanced NPC in the IMRT era.

PMID- 29187907
TI  - Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting
      as a ceRNA for microRNA-215 to regulate ZEB2 expression.
AB  - Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors,
      including colorectal cancer (CRC). However, the role of lncRNA in CRC liver
      metastasis remains unclear. Methods: a microarray was performed to identify the
      differentially expressed lncRNAs between CRC tissues with and without liver
      metastasis. Survival analysis was evaluated using the Kaplan-Meier method and
      assessed using the log-rank test. In vitro and in vivo assays were preformed to
      explore the biological effects of the differentially expressed lncRNA in CRC
      cells. Results: the lncRNA UICLM (up-regulated in colorectal cancer liver
      metastasis) was significantly up-regulated in cases of CRC with liver metastasis.
      Moreover, UICLM expression was higher in CRC tissues than in normal tissues, and
      UICLM expression was associated with poor patient survival. Knockdown of UICLM
      inhibited CRC cell proliferation, invasion, epithelial-mesenchymal transition
      (EMT) and CRC stem cell formation in vitro as well as tumor growth and liver
      metastasis in vivo. Ectopic expression of UICLM promoted CRC cell proliferation
      and invasion. Mechanistic investigations revealed that UICLM induced its
      biological effects by regulating ZEB2, as the oncogenesis facilitated by UICLM
      was inhibited by ZEB2 depletion. Further study indicated that UICLM acted as a
      competing endogenous RNA (ceRNA) for miR-215 to regulate ZEB2 expression.
      Conclusions: taken together, our findings demonstrate how UICLM induces CRC liver
      metastasis and may offer a novel prognostic marker and therapeutic target for
      this disease.

PMID- 29187910
TI  - Injection of nanoparticles into cloven-hoof animals: Asking for trouble.
AB  - This article aims at alerting scientists working with nanoparticles or
      microparticles about the specific adverse reactions due to the intravascular
      pulmonary macrophages present in pigs and other cloven-hoof animals, but not in
      humans. The history of a 25-year old study of an ultrasound contrast agent is
      used to illustrate these differences.

PMID- 29187908
TI  - Interleukin-6 Mediates Post-Infarct Repair by Cardiac Explant-Derived Stem Cells.
AB  - : Although patient-sourced cardiac explant-derived stem cells (EDCs) provide an
      exogenous source of new cardiomyocytes post-myocardial infarction, poor long-term
      engraftment indicates that the benefits seen in clinical trials are likely
      paracrine-mediated. Of the numerous cytokines produced by EDCs, interleukin-6 (IL
      6) is the most abundant; however, its role in cardiac repair is uncertain. In
      this study, a custom short-hairpin oligonucleotide lentivirus was used to
      knockdown IL-6 in human EDCs, revealing an unexpected pro-healing role for the
      cytokine. METHODS: EDCs were cultured from atrial appendages donated by patients
      undergoing clinically indicated cardiac surgery. The effects of lentiviral
      mediated knockdown of IL-6 was evaluated using in vitro and in vivo models of
      myocardial ischemia. RESULTS: Silencing IL-6 in EDCs abrogated much of the
      benefits conferred by cell transplantation and revealed that IL-6 prompts cardiac
      fibroblasts and macrophages to reduce myocardial scarring while increasing the
      generation of new cardiomyocytes and recruitment of blood stem cells.
      CONCLUSIONS: This study suggests that IL-6 plays a pivotal role in EDC-mediated
      cardiac repair and may provide a means of increasing cell-mediated repair of
      ischemic myocardium.

PMID- 29187909
TI  - A New Theranostic System Based on Endoglin Aptamer Conjugated Fluorescent Silica
      Nanoparticles.
AB  - Background: Tumor vessels can potentially serve as diagnostic, prognostic and
      therapeutic targets for solid tumors. Fluorescent dyes are commonly used as
      biological indicators, while photobleaching seriously hinders their application.
      In this study, we aim to generate a fluorescent silica nanoparticles (FSiNPs)
      theranostic system marked by the mouse endgolin (mEND) aptamer, YQ26. Methods: A
      highly specific YQ26 was selected by using gene-modified cell line-based SELEX
      technique. FSiNPs were prepared via the reverse microemulsion method. The YQ26
      FSiNPs theranostic system was developed by combining YQ26 with the FSiNPs for in
      vivo tumor imaging, treatment and monitoring. Results: Both in vitro experiments
      (i.e. cellular and tumor tissue targeting assays) and in vivo animal studies
      (i.e. in vivo imaging and antitumor efficacy of YQ26-FSiNPs) clearly demonstrated
      that YQ26-FSiNPs could achieve prominently high targeting efficiency and
      therapeutic effects via aptamer YQ26-mediated binding to endoglin (END) molecule.
      Conclusion: This simple, sensitive, and specific YQ26-FSiNPs theranostic system
      has a great potential for clinical tumor targeting imaging and treatment.

PMID- 29187911
TI  - Oval Cells Contribute to Fibrogenesis of Marginal Liver Grafts under Stepwise
      Regulation of Aldose Reductase and Notch Signaling.
AB  - Background and Aims: Expanded donor criteria poses increased risk for late phase
      complications such as fibrosis that lead to graft dysfunction in liver
      transplantation. There remains a need to elucidate the precise mechanisms of post
      transplant liver damage in order to improve the long-term outcomes of marginal
      liver grafts. In this study, we aimed to examine the role of oval cells in
      fibrogenic development of marginal liver grafts and explore the underlying
      mechanisms. Methods: Using an orthotopic rat liver transplantation model and
      human post-transplant liver biopsy tissues, the dynamics of oval cells in
      marginal liver grafts was evaluated by the platform integrating immuno-labeling
      techniques and ultrastructure examination. Underlying mechanisms were further
      explored in oval cells and an Aldose reductase (AR) knockout mouse model
      simulating marginal graft injury. Results: We demonstrated that activation of
      aldose reductase initiated oval cell proliferation in small-for-size fatty grafts
      during ductular reaction at the early phase after transplantation. These
      proliferative oval cells subsequently showed prevailing biliary differentiation
      and exhibited features of mesenchymal transition including dynamically co
      expressing epithelial and mesenchymal markers, developing microstructures for
      extra-cellular matrix degradation (podosomes) or cell migration (filopodia and
      blebs), and acquiring the capacity in collagen production. Mechanistic studies
      further indicated that transition of oval cell-derived biliary cells toward
      mesenchymal phenotype ensued fibrogenesis in marginal grafts under the regulation
      of notch signaling pathway. Conclusions: Oval cell activation and their
      subsequent lineage commitment contribute to post-transplant fibrogenesis of small
      for-size fatty liver grafts. Interventions targeting oval cell dynamics may serve
      as potential strategies to refine current clinical management.

PMID- 29187913
TI  - An online monitor of the oxidative capacity of aerosols (o-MOCA).
AB  - The capacity of airborne particulate matter to generate reactive oxygen species
      (ROS) has been correlated with the generation of oxidative stress both in vitro
      and in vivo. The cellular damage from oxidative stress, and by implication with
      ROS, is associated with several common diseases, such as asthma and chronic
      obstructive pulmonary disease (COPD), and some neurological diseases. Yet
      currently available chemical and in vitro assays to determine the oxidative
      capacity of ambient particles require large samples, analyses are typically done
      offline, and the results are not immediate. Here we report the development of an
      online monitor of the oxidative capacity of aerosols (o-MOCA) to provide online,
      time-resolved assessment of the capacity of airborne particles to generate ROS.
      Our approach combines the Liquid Spot Sampler (LSS), which collects particles
      directly into small volumes of liquid, and a chemical module optimized for online
      measurement of the oxidative capacity of aerosol using the dithiothreitol (DTT)
      assay. The LSS uses a three-stage, laminar-flow water condensation approach to
      enable the collection of particles as small as 5 nm into liquid. The DTT assay
      has been improved to allow the online, time-resolved analysis of samples
      collected with the LSS but could be adapted to other collection methods or
      offline analysis of liquid extracts. The o-MOCA was optimized and its performance
      evaluated using the 9,10-phenanthraquinone (PQ) as a standard redox-active
      compound. Laboratory testing shows minimum interferences or carryover between
      consecutive samples, low blanks, and a reproducible, linear response between the
      DTT consumption rate (nmol min-1) and PQ concentration (MUM). The calculated
      limit of detection for o-MOCA was 0.15 nmol min-1. The system was validated with
      a diesel exhaust particle (DEP) extract, previously characterized and used for
      the development, improvement, and validation of the standard DTT analysis. The
      DTT consumption rates (nmol min-1) obtained with the o-MOCA were within
      experimental uncertainties of those previously reported for these DEP samples. In
      ambient air testing, the fully automated o-MOCA was run unattended for 3 days
      with 3 h time resolution and showed a diurnal and daily variability in the
      measured consumption rates (nmol min-1 m-3).

PMID- 29187914
TI  - Phonological and Semantic Cues to Learning from Word-Types.
AB  - Word-types represent the primary form of data for many models of phonological
      learning, and they often predict performance in psycholinguistic tasks. Word
      types are often tacitly defined as phonologically unique words. Yet, an explicit
      test of this definition is lacking, and natural language patterning suggests that
      word meaning could also act as a cue to word-type status. This possibility was
      tested in a statistical phonotactic learning experiment in which phonological and
      semantic properties of word-types varied. During familiarization, the learning
      targets-word-medial consonant sequences-were instantiated either by four related
      word-types or by just one word-type (the experimental frequency factor). The
      expectation was that more word-types would lead participants to generalize the
      target sequences. Regarding semantic cues, related word-types were either
      associated with different referents or all with a single referent. Regarding
      phonological cues, related word-types differed from each other by one, two, or
      more phonemes. At test, participants rated novel wordforms for their similarity
      to the familiarization words. When participants heard four related word-types,
      they gave higher ratings to test words with the same consonant sequences,
      irrespective of the phonological and semantic manipulations. The results support
      the existing phonological definition of word-types.

PMID- 29187915
TI  - Does Love Influence Athletic Performance? The Perspectives of Olympic Athletes.
AB  - In this brief report, we provide an initial account of the association between
      love and athletic performance from the perspective of Olympic athletes. We posit
      that Romantic Passionate Love (RPL) and athletic performance may both involve the
      reward-motivation system of the brain. Based on this premise, we explored whether
      activation in one domain (love) might influence the other (sport). Our
      investigation was framed using Sternberg's triangular theory of love. Twenty
      Olympic athletes representing different sports were interviewed at the Games.
      Most athletes (n = 15) reported that their performance was better while in love;
      however, qualitative responses suggested that the benefits were correlated with
      rather than resulting from RPL. Although the athletes were provided with a
      definition of RPL and affirmed that their relationship met the criteria,
      interview responses reflected companionate rather than passionate love,
      suggesting that RPL may be differentially conceptualized across cultures. The
      study provides preliminary data that may be used to inform and refine future work
      on this topic.

PMID- 29187912
TI  - Cell-cycle-specific Cellular Responses to Sonoporation.
AB  - Microbubble-mediated sonoporation has shown its great potential in facilitating
      intracellular uptake of gene/drugs and other therapeutic agents that are
      otherwise difficult to enter cells. However, the biophysical mechanisms
      underlying microbubble-cell interactions remain unclear. Particularly, it is
      still a major challenge to get a comprehensive understanding of the impact of
      cell cycle phase on the cellular responses simultaneously occurring in cell
      membrane and cytoskeleton induced by microbubble sonoporation. Methods: Here,
      efficient synchronizations were performed to arrest human cervical epithelial
      carcinoma (HeLa) cells in individual cycle phases. The, topography and stiffness
      of synchronized cells were examined using atomic force microscopy. The variations
      in cell membrane permeabilization and cytoskeleton arrangement induced by
      sonoporation were analyzed simultaneously by a real-time fluorescence imaging
      system. Results: The results showed that G1-phase cells typically had the largest
      height and elastic modulus, while S-phase cells were generally the flattest and
      softest ones. Consequently, the S-Phase was found to be the preferred cycle for
      instantaneous sonoporation treatment, due to the greatest enhancement of membrane
      permeability and the fastest cytoskeleton disassembly at the early stage after
      sonoporation. Conclusion: The current findings may benefit ongoing efforts aiming
      to pursue rational utilization of microbubble-mediated sonoporation in cell cycle
      targeted gene/drug delivery for cancer therapy.

PMID- 29187916
TI  - [Epidemiological, clinical and therapeutic aspects of blunt abdominal trauma in
      patients undergoing surgery at the General Hospital of National Reference of
      N'Djamena, Chad: about 49 cases].
AB  - Introduction: Blunt abdominal traumas are common. Methods: We retrospectively
      reviewed the medical records of 49 patients with blunt abdominal trauma who
      underwent surgery at the General Hospital of National Reference of N'Djamena,
      Chad over a period of 5 years. Epidemiological, clinical and therapeutic
      parameters of patients were studied. Results: The study included 42 men and 7
      women, mean age 21.3 years. The causes of blunt abdominal traumas were: road
      traffic accidents in 61.2% of cases; wall collapses (14.3%); assaults (8.2%).
      Blunt abdominal traumas were more frequent in August (14.28%) and October
      (16.32%). The waiting time for admission in hospital was 6-12h in 43% of cases.
      At discharge, wounded patients used private car in 85.7% of cases. Clinically,
      patients were often hemodynamically stable (55.1%). Medical imaging was dominated
      by direct radiography of the abdomen (57.1%). The most observed lesions were
      those located only in the small intestine (16.32%) or related to that of the
      bladder (8.16%) and spleen (2.04%). Laparotomy was negative in 6.12% of cases.
      Morbidity (12.2%) was dominated by abdominal wall abscess. Mortality rate was
      6.1%. Conclusion: Road traffic accidents are the leading cause of blunt abdominal
      traumas. It is important to minimize delays in diagnosis, and treatment. Road
      safety measures should be implemented to prevent accidents.

PMID- 29187917
TI  - Multi-antibiotic resistant extended-spectrum beta-lactamase producing bacteria
      pose a challenge to the effective treatment of wound and skin infections.
AB  - Introduction: The increasing incidence of antibiotic resistant bacteria is a
      concern both to the clinicians and the patients due to obvious consequences such
      as treatment failures, prolonged patients' stay in hospital and nosocomial
      infections. The choice of the first antibiotic therapy in emergency wards in
      hospitals is usually not based on patient-specific microbial culture and
      susceptibility test result.This study is aimed at profiling extended-spectrum
      beta-lactamase (ESBL) producing bacteria associated with wound injuries and
      highlighting their multi-antibiotic resistance character. Methods: Sixty-three
      wound swab samples were collected and cultured on nutrient agar and on selective
      media. Evaluation for ESBL production was by phenotypic method while the
      antibiogram screening was by disc-diffusion. Results: The wounds evaluated were
      diabetic sore (14), cancer wounds (12), surgical wounds (17), wounds due to road
      traffic accidents (10) and wounds from fire burn (10). The result showed that 61
      wounds were infected and the prevalence of the infecting pathogens was
      Escherichia coli 17.46%, Klebsiella Pneumonia 14.28%, Salmonella typhi 12.79%,
      Pseudomonas Aeruginosa 34.92% and Staphylococcus aureus 17.46%. Thirty four
      (55.74 %) isolates were ESBL producers, greater than 50% of which being
      Pseudomonas Aeruginosa. The antibiogram study of the ESBL producers showed multi
      drug resistance with resistance highest against ampicillin (100%), followed by
      cephalosporins: cefuroxime (94.12%) and ceftriaxone (61.76%). No resistance was
      recorded against the beta-lactamase inhibitors: amoxicillin/clavulanate and
      ceftriaxone/sulbactam. There was a high incidence (55.74 %) of ESBL-producing
      microbes in the wounds. The isolates were mostly multi-antibiotic resistant.
      Conclusion: Multi-drug resistant ESBL-producing bacteria are common in wound
      infections in the community. However, amoxicillin/clavulanate or
      ceftriaxone/sulbactam may be used to treat most patients with such infections in
      the hospital. This may guide antibiotic selection and use in trauma, most
      especially in resource limited countries where laboratory test is unaffordable
      for a majority of patients.

PMID- 29187918
TI  - Evaluation of wetting ability of five new saliva substitutes on heat-polymerized
      acrylic resin for retention of complete dentures in dry mouth patients: a
      comparative study.
AB  - Introduction: The aim of this study was to evaluate & compare the wetting ability
      of five saliva substitutes & distilled water on heat-polymerized acrylic resin.
      Contact angle of the saliva substitute on denture base can be taken as an
      indicator of wettability. Good wetting of heat-polymerized acrylic resin is
      critical for optimum retention of complete dentures. Methods: Two hundred & forty
      samples of heat-polymerized acrylic resin were fabricated using conventional
      method. 240 samples divided into 6 groups with 40 samples in each group.
      Advancing & Receding contact angles were measured using Contact Angle Goniometer
      & DSA4 software analysis. Results: Anova test was carried out to test the
      significance in difference of contact angle values in the six groups. The mean of
      advancing angle values & mean of receding angle values of all the six groups has
      shown statistically significant difference between the groups. The mean of angle
      of hysteresis values of all the six groups are statistically not significant
      between the groups. A multiple comparison using Bonferroni's test was carried out
      to verify the significance of difference between the contact angles in a pair of
      groups. Statistically significant difference was seen when Aqwet (Group II) was
      compared to Distilled water (Group I), Wet Mouth (Group III), E-Saliva (Group
      IV), Biotene (Group V), and Moi-Stir (Group VI). Conclusion: The contact angles
      of five saliva substitutes and distilled water were measured and compared. Group
      II (AQWET) has the lowest advancing and receding contact angle values and the
      highest angle of hysteresis on heat-polymerized acrylic resin. Based on contact
      angle values, Group II (AQWET) has the best wetting ability on heat-cured acrylic
      resins. The ability of saliva to wet the denture surface is one of the most
      important properties for complete denture retention in dry mouth cases.

PMID- 29187919
TI  - Factors affecting access to information on routine immunization among mothers of
      under 5 children in Kaduna State Nigeria, 2015.
AB  - Introduction: Immunization is one of the most effective interventions to prevent
      disease and early child death. A substantial number of children worldwide do not
      complete immunization schedules because neither health services nor conventional
      communication mechanisms regularly reach their communities. Knowledge and
      perception of mothers/caregivers regarding VPDs influence demand and utilization
      of immunization services. We examined the associations between knowledge,
      perception and information on routine immunization received by mothers/caregivers
      in Kaduna State. Methods: We enrolled 379 eligible caregivers in a community
      based cross-sectional study. We sampled respondents using multistage sampling
      technique. We collected data on socio-demographic characteristics; knowledge and
      perception on routine immunization using semi-structured interviewer-administered
      questionnaire. We conducted bivariate analysis and logistic regression using Epi
      InfoTM version 7 at 5% level of significance. Results: Mean age of respondents
      was 28.6 years (standard deviation=+/-6.6 years), 34% completed secondary school,
      65% were unemployed, 49% lived in rural settlements. Among respondents' children
      53.3% were females and 62.8% fell within 2nd-5th birth order. Only 15.6% of these
      children were fully immunized. Seventy-five percent of respondent did not obtain
      information on routine immunization within 12 months prior to the study. About
      64% had unsatisfactory knowledge while 55.4% exhibited poor perceptions regarding
      routine immunization. Commonest source of information was radio (61.61%). On
      logistic regression educated participants (Adjusted odds ratio (AOR)=1.9, 95% CI:
      1.1-3.3), mothers' perception (AOR=2.6, 95% CI: 1.5-4.5) and monogamous family
      setting (AOR=2.4, 95% CI: 0.2-0.6) were likely to have obtained information on
      routine immunization. Conclusion: There is low access to information, poor
      maternal knowledge on routine immunization with low vaccination coverage in this
      community. Efforts should be made by the Governments to scale up sensitization of
      mothers/caregivers to improve their knowledge on routine immunization through
      radio jingles.

PMID- 29187920
TI  - [Benign tumors of the breast in the department of senology at the University
      Hospital Aristide Le Dantec, Dakar (Senegal)].
AB  - Introduction: This study aimed to identify the epidemiological, clinical and
      therapeutic features of benign tumors of the breast treated in the department of
      senology at the university hospital Aristide Le Dantec, Dakar. Methods: We
      conducted a cross-sectional, descriptive and analytical study of 220 patients
      treated in the Department of Senology at the University Hospital Aristide Le
      Dantec, Dakar over the period from 1 January 2008 to 31 December 2013. Results:
      220 patients out of 984 consultants had benign tumor of the breast (22.5%).
      Benign tumors of the breast accounted for 58.2% of tumor pathologies. The average
      age was 24 years. The age group 11-30 years was the most represented (70%). The
      quasi-totality of patients were women of childbearing age (95%), 58.6% were
      nulliparous women. The main reason for consultation was a breast mass in 94.5% of
      cases. The left side was most often affected (49.5%), especially the upper outer
      quadrant (41.6%). 145 patients (65.9% of cases) underwent ultrasound. Cytologic
      examination showed conjunctival epithelial hyperplasia in almost all cases
      (96.1%). 44 women underwent histologic examination, which confirmed the
      histologic nature of the lesions. Fibroadenoma and fibrocystic changes were the
      most retained diagnoses, accounting for 86.3% and 5.9% respectively. 28 patients
      (12.7%) underwent lumpectomy, all tumor types were taken together. The majority
      of patients had follow-up appointments within 3 months, with favorable outcome.
      Conclusion: Benign tumors are very frequent in senology consultations. The
      recommended diagnostic approach combines the clinico-radio-cytological triad and,
      in case of doubt or discrepancy, biopsy or surgical resection are essential.
      Surgery is not always the treatment of choice. This is based on the nature of the
      tumor.

PMID- 29187921
TI  - Giant gastric trichobezoar in a young female with Rapunzel syndrome: case report.
AB  - Rapunzel syndrome is an extremely rare complication of a gastric trichobezoar in.
      We report here the unusual case of a case of a 16 years old girl presented with
      severe abdominal pain and vomiting. Clinical examination revealed a malnourished
      girl, with presence of a mobile and sensitive abdominal mass of 20x15 cm witch
      filled the upper quadrant. An abdominal computed tomography scan showed a
      heterogeneous mass occupying the whole stomach cavity with extension into the
      third portion of the duodenum. A diagnostic of giant trichobezoar is suspected
      after further questioning reveling a trichotillomania, trichophagia and
      onychophagia. The removal of the trichobezoar endoscopically failed and it was
      possible to pull only few fibers of hair to comfort the diagnostic. She was
      subjected to an exploratory laparotomy. An antral gastrostomy were performed and
      a 25x10x7 cm trichobezoar was extracted. The patient had an uneventful
      postoperative outcome and was derived to psychiatry. Rapunzel syndrome is an
      uncommon trichobezoar, it's commonly found in young females usually with an
      underlying psychiatric disorder. Management requires gastrotomy. A psychiatric
      assessment and a long-term follow-up are advocated as a regular part of treatment
      to prevent recurrence.

PMID- 29187922
TI  - [Assessment of a supervision grid being used in the laboratories of cutaneous
      leishmaniasis in Morocco].
AB  - Introduction: The aim of our study was to assess a standardized supervisory grid
      as a new supervision tool being used in the laboratories of leishmaniasis.
      Methods: We conducted a pilot trial to evaluate the ongoing performances of seven
      provincial laboratories, in four provinces in Morocco, over a period of two
      years, between 2006 and 2014. This study detailed the situation in provincial
      laboratories before and after the implementation of the supervisory grid. A total
      of twenty-one grids were analyzed. Results: In 2006, the results clearly showed a
      poor performance of laboratories: need for training (41.6%), staff performing
      skin biopsy (25%), shortage of materials and reagents (65%), non-compliant
      document and local management (85%). Several corrective actions were conducted by
      the National Reference Laboratory (LNRL) of Leishmaniasis during the study
      period. In 2014, the LNRL recorded a net improvement of the performances of the
      laboratories. The need for training, the quality of the biopsy, the supply of
      tools and reagents were met and an effective coordination activity was
      established between the LNRL and the provincial laboratories. Conclusion: This
      trial shows the effectiveness of the grid as a high quality supervisory tool and
      as a cornerstone of making progress on fight programs against leishmaniases.

PMID- 29187923
TI  - [IIA2-Y-type urethral duplication].
AB  - Urethral duplications are extremely rare congenital malformations. The most used
      classification is that of Effmann and Lebowitz, describing 6 types of urethral
      duplications. The under type IIA2-Y is one of the most rare duplications
      corresponding to duplicated urethra originating from the bladder neck and
      extending toward the ectopic perineal or anal insertion. We here report the case
      of a 32 year patient, with no previous personal history, suffering from urinary
      leakage during and after urination since childhood. Clinical examination showed a
      bottleneck at the level to the perineum initially suggesting urethral fistula.
      However, the absence of fistula-associated urinary disorders as well as urinary
      leakage since childhood refuted this assumption. The patient underwent
      Micturating Retrograde Urethrocistography after perineal orifice catheterization
      confirming well systematized tract. Surgical exploration was based on excision of
      the duplicate urethra after hydrophilic catheterization by inserting hydrophilic
      guidewire up to its anastomosis at the level of the prostate. The examination of
      the surgical specimen confirmed the diagnosis of supernumerary urethra.

PMID- 29187924
TI  - Social and cultural barriers to husbands' involvement in maternal health in rural
      Gambia.
AB  - Introduction: While many studies have documented a number of socio-cultural
      barriers to male involvement in maternal health, in The Gambia very little
      information is known about the social and cultural practices that characterized
      male involvement in maternal health. This study aims to explore some of the
      underlying social and cultural factors affecting husbands' involvement in
      maternal health issues pertaining to pregnancy and delivery in rural Gambia.
      Methods: Five focus group discussions and six in-depth interviews were conducted
      among rural men and traditional birth attendants in five areas of rural Gambia.
      The discussion was directed to the roles of male partners in pregnancy and
      delivery and the difficulties they face regarding taking care of their wives. The
      data resulting from the discussion was audio-recorded, transcribed verbatim, and
      analyzed thematically. Results: In general, rural Gambian men and traditional
      birth attendants (TBAs) reported that husbands' involvement in maternal health is
      highly desirable, but is influenced by many factors, such as the traditional
      conceptualization associated with pregnancy and delivery as women's domain. In
      addition, many men do not believe that pregnancy chores warrant their efforts
      compared to other competing social responsibilities. This issue may be more
      complicated in polygamous marriages where there is rivalry among co-wives and in
      neighborhoods where men who help with house chores may be subjected to mockery.
      Conclusion: These findings suggest that husbands' involvement in maternal health
      in The Gambia is influenced by the prevailing social and cultural practices of
      gender role and norms, which are also at the root of maternal health problems.

PMID- 29187925
TI  - A novel approach to treat peri implantitis with the help of PRF.
AB  - A new field of biomedical science, known as tissue engineering, applies the
      principles of biology and engineering to the development of functional
      substitutes for tissues and organs. Little is known about the influence of
      Keratinised Mucosa dimension around implants on the soft and hard tissue health
      The purpose of this case report is to understand the importance of healthy tissue
      around the implants for long term success and how biomimetic materials like PRF
      Membrane can be incorporated in treatment plan as an important modality in
      selected cases.

PMID- 29187926
TI  - [Management of moderate and severe dysthyroid orbitopathy: about 22 cases].
AB  - Our study aimed to describe the therapeutic management of moderate and severe
      dysthyroid orbitopathies and to evaluate the factors associated with optic
      neuropathy as well as the prognostic factors of poor visual outcome using a
      statistical analysis. We conducted a retrospective study of 22 patients
      presenting with moderate to severe dysthyroid orbitopathy in at least one eye and
      hospitalized in the Department of Ophthalmology at the University Hospital Farhat
      Hached, Sousse over the period from 1998 to 2015. Therapeutic indications were
      based on activity and severity criteria of the Eugogo (European Group On Graves'
      Orbitopathy) as well as on the assessment of prognostic factors of poor visual
      outcome. The average age of our patients was 40 years, with a slight male
      predominance (54.5%). 68.2% of patients were euthyroid, 18.2% had a history of
      smoking. The most significantly associated factor with neuropathy was a
      compression in the orbital apex (p = 0.03). Treatment was based on intravenous
      corticosteroid therapy and/or orbital decompression based on disease activity and
      severity. Overall evolution after treatment was marked by an improvement in
      inflammatory signs and by the reduction of exophthalmia. Visual prognosis was
      worse in elderly patients (p = 0.0001), male sex (p = 0.03) and treated by
      iratherapy (p = 0.04). Given the limits of a retrospective study, our results
      were generally consistent with the literature. The assessment and the management
      of dysthyroid orbitopathy are not well understood. Cohort, probably multicenter
      studies should be conducted to improve its management.

PMID- 29187927
TI  - Our chairman is very efficient: community participation in the delivery of
      primary health care in Ibadan, Southwest Nigeria.
AB  - Introduction: Community participation is rapidly being viewed as a requirement
      for the successful acceptance of health services; it integrates a complicated
      process which involves customs, beliefs, culture and power relations, not only
      structures and policies. Yet, there is a wide knowledge gap and changes favouring
      community participation in primary health care is still minimal. This study aims
      to assess the process indicators and other factors influencing community
      participation in the delivery of primary health care. Methods: This descriptive
      cross-sectional study using qualitative methods was conducted in Ibadan South
      East Local Government Area of Oyo State, Nigeria between July and September,
      2015. The interview and Focus Group Discussion guides centred around five
      participation indicators of needs assessment, leadership, resource mobilization,
      organization and management was used to collect data. A total of 12 in-depth
      interviews and four FGDs were conducted among male and female respondents
      consisting PHC service providers and community members purposively selected from
      four wards of the LGA. Spidergrams were constructed to visualize the levels of
      community participation from respondents' opinions. Results: About 51.1% of the
      45 respondents (with mean age 45.5 +/- 8.09 years) were males. The respondents
      view community participation in the delivery of PHC in the LGA as being wide
      (open). Majority of the service users believe and agree that the level of
      community participation in their wards is about average while the service
      providers believed that participation was very high. However, respondents
      identified female representation, collaboration with pre-existing community
      structures, top-down and bottom-up approach to service delivery as factors
      affecting community participation in PHC delivery. Conclusion: This study
      provides a baseline data on community participation in the delivery of primary
      health care. Community participation is still an important principle in the
      delivery of primary health care and it guarantees the positive changes desired in
      the uptake and sustainability of primary health care programmes.

PMID- 29187928
TI  - Hormone-receptor expression status of epithelial ovarian cancer in Ibadan, South
      western Nigeria.
AB  - Introduction: Epidemiological evidence strongly suggests that steroid hormones
      are implicated in the pathogenesis of ovarian cancer. Estrogen receptor (ER) and
      Progesterone receptor (PR) are prognostic indicators for a number of epithelial
      tumors and may play the same role in ovarian cancers. This study aims to evaluate
      the expression of ER and PR in epithelial ovarian cancer (EOC) in an African
      population and compare it with other prognostic factors such as age,
      International Federation of Gynaecology and Obstetrics (FIGO) stage, grade and
      histological subtype. Methods: Ninety cases of histologically confirmed EOC were
      reviewed. Immunohistochemistry was used to assess their ER and PR expression
      status and was then compared with other demographic variables using statistical
      methods, with level of significance set at p < 0.05. Results: 30.2% and 8.3% of
      serous and mucinous carcinomas respectively were ER positive while 41.2% and
      22.5% of both tumour types were PR positive. One of the two endometrioid
      carcinomas showed PR expression but neither were positive for ER. The only case
      of Brenner tumour in the series was ER positive but negative for PR. There was a
      significant association between ER and the histological subtypes (p = 0.042)
      while no significant association was found between PR expression and histological
      subtypes (p = 0.650). No significant association was found between hormone
      receptor status, age and stage of the EOC. Conclusion: The study showed a lower
      ER expression in serous carcinoma compared to large cohorts from developed
      countries. Future translational studies could be used to determine response of
      EOC to endocrine therapy.

PMID- 29187929
TI  - [Role of GeneXpert MTB/RIF test in the screening for pulmonary tuberculosis at
      the General Referral Provincial Hospital of Bukavu, in the East of the Democratic
      Republic of the Congo: balance after 10 months of use].
AB  - Introduction: In sub-Saharan Africa, diagnostic methods for tuberculosis are
      inadequate and are essentially based on microscopy. They constitute a real
      obstacle to the control of tuberculosis. This study aimed to evaluate the
      performance of GeneXpert MTB/RIF test compared to classical Ziehl-Neelsen
      staining at the the general referral provincial hospital of Bukavu, in the east
      of the Democratic Republic of the Congo after 10 months of use. Methods: The
      results of Ziehl-Neelsen staining and GeneXpert MTB/RIF molecular biology test
      performed in 452 patients with suspected tuberculosis were collected. This study
      compares the validity of these different diagnostic tests in the detection of
      tuberculosis. Results: In the entire group, the frequency of the pulmonary
      tuberculosis was 16.3%. The positivity rate was significantly higher in GeneXpert
      MTB/RIF test than in Ziehl-Neelsen staining in the entire group (15.9% vs 9.3%, p
      = 0.03) and in HIV seropositive patients (52.0% vs 24.0%; p = 0.007). However,
      the sensitivity of GeneXpert MTB/RIF test compared to that in Ziehl-Neelsen
      staining wasn't maximum (95.2%). Finally, GeneXpert MTB/RIF test detected
      rifampicin resistance in 20.8%. Conclusion: This study confirms the superiority
      of GeneXpert MTB/RIF test compared to Ziehl-Neelsen staining in the detection of
      tuberculosis and in the prediction of multi-resistance. Its systematic use
      coupled with Ziehl-Neelsen staining would better control tuberculosis in sub
      Saharan Africa.

PMID- 29187930
TI  - Stages of development of traditional simulation unit of surgery for manual extra
      capsular cataract extraction in sub-Saharan African region.
AB  - The manual extracapsular extraction of the lens is the surgical technique that is
      most practiced for the treatment of cataract in sub-Saharan Africa. Learning this
      technique requires the creation of a surgical simulation unit within training
      institutes. We describe the development stages of a traditional simulation unit.
      For this purpose, we present a description of four steps involved in the
      development of a simulation unit for cataract surgery: the physical creation of
      the room, the aseptic and antisepsis conditions, the management of the eyes, the
      development of a curriculum and the administrative policies.

PMID- 29187931
TI  - [Diagnostic and evolutionary profile of multiple myeloma in Senegal: monocentric
      study conducted from 2005 to 2016].
AB  - Introduction: Accessibility to innovative multiple myeloma therapies is limited
      in sub-Saharan Africa. This study aimed to describe the diagnostic and
      evolutionary features observed during treatment of our patients with myeloma.
      Methods: We conducted a retrospective, descriptive, analytical study (2005 -
      2016) of patients with myeloma included in the study based on International
      Myeloma Working Group (IMWG) Criteria (2003,2014) at the Hopital Aristide Le
      Dantec (Senegal). Results: We collected data from 136 medical records (69 men, 67
      women) of patients with an average age of 59 years +/- 10.1 years, who were less
      than 65 years of age in 69.1% of cases. Tell-tale signs included bone pain
      (96.3%), renal failure (36.8%), infection (23.5%), pathological fracture (17.6%),
      spinal cord compression (16.9%) and malignant hypercalcaemia (16.2%). Isotopic
      antiglobulin test showed that anti-IgG could be detected in 61.3% of cases and
      Kappa in 65% of cases. Patients were classified stage III (59.4%) and I-II
      (40.6%)of the index staging system. The median survival of patients under
      conventional traitement (Mephalan-Prednisone: 67.6%, innovative: 5.9%) was 20
      months (1-78 months). Survival rates are better in the absence of neurological
      and infectious complications and for patients with score I-II of the index
      Staging System. Conclusion: In our study, multiple myeloma was frequently
      diagnosed before age 65, at advanced stage of tumor mass. Early detection and
      access to adequate therapies could improve overall survival.

PMID- 29187932
TI  - [Immature teratoma of the ovary: about a case].
AB  - Ovarian teratomas are tumors resulting from pluripotent germ cells. We here
      describe 3 different types of teratomas: mature, immature and monodermal
      teratomas. Immature teratoma accounts for less than 1% of ovarian cancers and
      mainly affects young subjects. We report the case of a 25 year female patient,
      admitted with abdomino pelvic mass. She underwent ultrasound and a pelvic CT scan
      followed by conservative treatment based on left annexectomy associated with
      multiple biopsies. Anatomopathological examination showed immature ovarian
      teratoma. Patient's treatment was supplemented by a hysterectomy with lumbo
      aortic curage and omentectomy. We highlight, through this study and review of the
      literature, the predisposing factors for this type of rare and severe tumor and
      the radiological features suggesting these rare histological types of ovarian
      tumors, in order to improve the prognosis and multidisciplinary management of
      patients.

PMID- 29187933
TI  - Intraperitoneal recurrence of renal haemangiopericytoma.

PMID- 29187935
TI  - [Haemorrhagic stroke of the brainstem secondary to postpartum eclampsia: about a
      case and literature review].
AB  - Strokes are rare but severe accidents during pregnancy and post-partum period.
      They are responsible for high mortality and morbidity rates. Pre-eclampsia,
      eclampsia, and strokes are significantly related. Endothelial dysfunction,
      alteration of brain self-regulation and severe hypertension are, probably, the
      cause of many strokes in pregnant women and during postpartum period. We report a
      case of hemorrhagic stroke of the brainstem in a nonmonitored 21-year old patient
      at 38 weeks pregnant admitted with severe preeclampsia complicated by eclampsia
      and then by haemorrhagic stroke of the brainstem on the second post-operative day
      after cesarean section performed due to suspicion of retroplacental haematoma
      arisen since her admission. Intracerebral hemorrhage is a rare but severe
      complication in post-partum women. Several studies are underway to fill the gaps
      of knowledge involved in the management of pre-eclamptic patients with
      neurological complications.

PMID- 29187934
TI  - [Persistence of the 5th aortic arch associated with interruption of the aortic
      arch].
AB  - We report a case of persistence of the 5th aortic arch associated with total
      interruption of the aortic arch. This clinical case shows the diagnostic pitfall
      of the persistence of the 5th aortic arch and its beneficial hemodynamic effect.
      Preoperative clinical picture was misleading, due to the persistence of femoral
      pulses and clinical signs of left-to-right shunt via a wide ductus arteriosus.
      The diagnosis was intraoperatively adjusted on the basis of blood pressure
      monitoring using catheter placed into the femoral artery.

PMID- 29187936
TI  - Mucin expression patterns in histological grades of colonic cancers in Ghanaian
      population.
AB  - Introduction: Myriad roles of mucins in normal tissues have been well documented,
      including lubrication of the epithelial surfaces; protection from physical
      damage; facilitation in cell-cell signaling and suppression of inflammatory
      activity. Pathological expression of mucins has been noted in cancer development
      and progression. This study sought to identify and quantify the types of mucins
      produced during various histological grades of colon cancer and to assess the
      diagnostic significance. Methods: Formalin fixed, paraffin-embedded tissue
      blocks, comprising three (3) normal colon and twenty-two (22) colon cancer
      tissues, were retrieved from the archives of the histopathology department of the
      Komfo Anokye Teaching Hospital. They were stained with Haematoxylin and eosin
      (H&E) for diagnosis and grading of tumours. Tissues were pre-digested with
      diastase and stained with Alcian blue (pH 2.5)/Periodic Acid Schiff to
      characterize the mucin variants present. Results: Our findings indicated that
      normal colonic tissues expressed exceptionally high amount of acid mucin and low
      amount of neutral mucin. However, there was a general decrease in mucin
      expression in colon cancers compared to normal colon tissues. Additional findings
      suggested that as cancer progresses from low grade to high grade of
      adenocarcinoma of the colon, there was generally a considerable decrease in the
      acid mucin production and an increase in the neutral mucin expression. In
      contrast, a sizeable subpopulation of high-grade adenocarcinomas of colon showed
      a rather opposite mucin expression pattern- increase in acid mucin and a decrease
      in neutral mucin. Conclusion: As colonic cancer progresses, there are
      corresponding changes in the mucin types and content such that there are decrease
      in acid mucin and increase in neutral mucin expressions.

PMID- 29187937
TI  - Safety culture in the maternity unit of hospitals in Ilam province, Iran: a
      census survey using HSOPSC tool.
AB  - Introduction: Improving quality of maternal care as well as patients' safety are
      two important issues in health-care service. Therefore, this study aimed to
      assess the culture of patient safety at maternity units. Methods: This cross
      sectional study was conducted among staffs working at maternity units in seven
      hospitals of Ilam city, Iran. The staffs included in this study were
      gynecologists and midwifes working in different positions including matron,
      supervisors, head of departments and staffs. Data were collected using the
      Hospital Survey on Patient Safety Culture (HSOPSC). Results: This study indicated
      that 59.1% of participants reported fair level of overall perceptions of safety
      and 67.1% declared that no event was reported during the past 12 months. The most
      positively perceived dimension of safety culture was teamwork within departments
      in view of managers (79.41) and personnel (81.10). However, the least positively
      perceived dimensions of safety culture was staffing levels. Conclusion: The
      current study revealed areas of strength (teamwork within departments) and
      weakness (staffing, punitive responses to error) among managers and personnel. In
      addition, we found that staffs in Ilam's hospitals accept the patient safety
      culture in maternity units, but, still are far away from excellent culture of
      patient safety. Therefore, it is necessary to promote culture of patient's safety
      among professions working in the maternity units of Ilam's hospitals.

PMID- 29187938
TI  - Review of toxoplasmosis in Morocco: seroprevalence and risk factors for
      toxoplasma infection among pregnant women and HIV- infected patients.
AB  - Toxoplasmosis is a disease caused by a protozoal parasite: Toxoplasma gondii.
      This infection can cause severe illness when the organism is contracted
      congenitally or when it is reactivated in immunosuppressed people. In this paper
      we review for the first time prevalence and risk factors of T. gondii among
      pregnant women and HIV-infected adults in Morocco. A systematic review
      methodology was used to consult three databases: Pub Med, Science Direct and
      Google Scholar dated until 2015, regarding prevalence data and risk factors of
      infection among pregnant women and people living with HIV. Data collection and
      eligibility criteria were established in this paper. No statistical method was
      employed in this study. Our review resulted in a total of 6 publications meeting
      the inclusion criteria of prevalence and risk factors of toxoplasmosis in
      Morocco. Seropositive rates of T. gondii infection reach up to 51% in pregnant
      women. Risk factors that were reported included contact with soil, lack of
      knowledge about toxoplasmosis, and a low educational level. For HIV-infected
      adults, the limited data show a 62.1% prevalence rate of T. gondii .According to
      our review, there is still very little information on toxoplasmosis disease in
      pregnant women and HIV infected patients in Morocco. Further research on
      toxoplasmosis is needed to better ascertain the human disease burden in Morocco.

PMID- 29187939
TI  - [The relationship between tumor recurrence and polymorphisms of hGPX1 and NRAMP1
      in superficial bladder cancer patients: a meta-analysis].
AB  - Introduction: Previous studies about the relationship between tumor recurrence
      and NRAMP1 and HGPX1 gene polymorphism in patients with non-muscle-invasive
      bladder cancer (NMIBC) showed inconsistent results. Methods: We conducted a
      systematic review of the literature on the basis of data from PubMed and China
      National Knowledge Infrastructure. According to the predefined selection
      criteria, the eligibility criteria for the studies found in the literature were
      assessed by two independent authors. The basic characteristics of the included
      studies and of data relevant to the meta-analysis were extracted. Patients?
      survival without recurrence was selected as the measure of effect of meta
      analysis. Results: Four publications were retained. Three studies evaluated the
      NRAMP1 D534N and three the hGPX1 Pro168Leu. Depending on the association between
      NRAMP1 D534N and tumor recurrence, the meta-analysis revealed no significant
      heterogeneity and the combined effect was 3.28 [1.77, 6.11]. Depending on the
      association between hGPX1 Pro198Leu and tumor recurrence, the meta-analysis
      showed significant heterogeneity and the combined effect was 1.12 [0.45, 2.77].
      Publication bias was uncertain, due to the limited number of included studies.The
      instability of the combined effects was reported. Conclusion: Very little data
      are available on the association between tumor recurrence and NRAMP1 D534N and
      hGPX1 Pro168Leu poolymorphisms in patients with NMIBC. The NRAMP1 D534N could
      increase the risk of recurrence, but hGPX1 Pro168Leu effect is not clear. A more
      thorough investigation should be conducted on a larger sample size in order to
      better explain this phenomenon.

PMID- 29187940
TI  - Unusual case of ruptured sinus of valsalva aneurysm in a pregnant woman.
AB  - Sinus of Valsalva aneurysms are extremely rare, and usually of a congenital
      nature. There are few documented cases of this condition during pregnancy, which
      renders unclear the therapeutic options. We here report the case of a 26 years
      old pregnant woman who was referred to our cardiac center for the evaluation of a
      heart murmur. The two-dimensional transthoracic echocardiography allowed quickly
      to establishthe diagnosis of a ruptured sinus of Valsalva aneurysm into the right
      ventricle. A successful surgical correction of the ruptured aneurysm was
      performed with patch repair.

PMID- 29187941
TI  - [Accidents of the everyday life (AcVC) in children in Dakar: about 201 cases].
AB  - Accidents of everyday life (AcVC) are common in children and can led to disabling
      injuries and death. This study aimed to analyze the epidemiological aspects of
      AcVC and the related injury mechanisms in Dakar. We conducted a descriptive,
      cross-sectional study conducted from 1 January 2013 to 30 June 2013. All the
      children victims of domestic accidents, sport and leisure accidents or school
      accidents were included. We studied some general parameters and some parameters
      related to each type of AcVC. Two hundred and one children were included,
      accounting for 27% of emergency consultations. There were 148 boys and 53 girls.
      Children less than 5 years of age were most affected (37.8%). Football and
      wrestling game were the main causes of AcVC. AcVC occur mainly at home (58.2%)
      and in the areas of sport and recreation (31.8%). The fractures predominated in
      the different types of AcVC: 54.9% of domestic accidents, 68.8% of sport and
      recreation accidents and 40% of school accidents. From an epidemiological
      perspective, our results are superimposable to literature. Fractures predominated
      contrary to literature where bruises were preponderant. Wrestling game is the
      main cause of these fractures, after football. The acquisition of knowledge about
      the epidemiological aspects of AcVC and the related injury mechanisms will allow
      for prevention campaigns in Dakar.

PMID- 29187942
TI  - [Double aortic arch: about two cases].
AB  - Double aortic arch is a rare anomaly of the aortic arch. It is due to the absence
      of involution of the caudal dorsal aorta. The disease usually begins to show
      itself in very early clinical signs, already detectable in the neonatal period.
      Angiography is of great interest to its diagnosis as well as to the choice of the
      therapeutic approach. Only surgical treatment allows to eliminate
      tracheoesophageal compression. Surgical mortality rate is low thanks to the
      progress of postoperative resuscitation. We here report two cases of double
      aortic arch in order to highlight the contribution of imaging in the difficult
      diagnosis of this anomaly.

PMID- 29187943
TI  - [Rare digestive tumors: gastrointestinal stromal tumors (GISTs): about a case of
      small bowel location and literature review].
AB  - Gastrointestinal stromal tumors (GISTs) are a rare group of mesenchymal tumors
      mainly occurring in the gastrointestinal tract. Previously, GISTs were classified
      as smooth muscle tumors also known as leiomyomas, leiomyosarcomas or
      leiomyoblastomas. However, since the advent of immunohistochemistry, GISTs have
      been diagnosed on the basis of the identification of c-kit-positive cells. We
      here report a case of stromal tumor of the small intestine in order to analyze it
      in the light of literature data and imaging results, which may suggest prebiopsy
      diagnosis as well as its therapeutic and prognostic peculiarities.

PMID- 29187944
TI  - Improving access to HbA1c in sub-Saharan Africa (IA3) cohort: cohort profile.
AB  - Introduction: Glycated haemoglobin (HbA1c) is the best surrogate of average blood
      glucose control in diabetic patients, and lowering HbA1c significantly reduces
      diabetes complications. Moreover, immediate feedback of HbA1c measurement to
      patients may improve control. However, HbA1c is unavailable in most parts of
      Africa, a continent with one of the highest burden of diabetes. To translate
      these evidences, we are conducting a multicentric project in 10 health care
      facilities in Guinea and Cameroon to evaluate the feasibility and one-year
      benefit of affordable HbA1c measurement with immediate feedback to patients on
      diabetes control and related outcomes. Participants: We consecutively enrolled
      patients with diabetes mellitus independently of the type of disease. We
      hypothesised an average 1%-decrease in HbA1c in a 1000-patient study population,
      with a 20% increase in the number of patients reaching treatment goals within 12
      months of intervention and follow-up. Findings to date: A total of 1, 349
      diabetic patients aged 56.2+/-12.6 years are enrolled (813 in Cameroon and 536 in
      Guinea) of whom 59.8% are women. The mean duration of diabetes is 7.4+/-6.3 years
      and baseline HbA1c is 9.7+/-2.6% in Guinea and 8.6+/-2.5% in Cameroon. Future
      plans: To investigate whether the introduction of routine HbA1c measurement with
      immediate feedback to patients and provision of relevant education would improve
      diabetes control after one year. The impact of the intervention on diabetes
      associated-complications and mortality warrant further assessment in the long
      term.

PMID- 29187945
TI  - Association between mean platelet volume and severity of rheumatoid arthritis.
AB  - Introduction: In recent years, it is suggested that platelet histogram indices,
      such as mean platelet volume (MPV) may be related to the activity of rheumatoid
      arthritis (RA). The aim of this study was to assess relationship between MPV and
      activity of rheumatoid arthritis. Methods: Sixty consecutive patients fulfilling
      the American College of Rheumatology (ACR) criteria for RA were recruited from
      the rheumatology outpatient clinics in Semnan, Iran. Current disease activity
      score (DAS-28 score) was assessed at baseline, 2 months and 4 months after the
      admission time and beginning of the treatment schedule. Complete blood count
      (including MPV), C-reactive protein (CRP) and ESR were measured in each visit.
      MPV was analyzed by the Cell Dyne 3500 automated blood cell counter. Results:
      There was a significant reduction in DAS-28 score within 4 months of total
      assessment (from 4.47 +/- 2.24 versus 3.18 +/- 1.55) (p < 0.001). There was no
      significant difference in MPV levels at the three study time points. No
      significant correlations were observed between the DAS-28 score and mean MPV
      levels at the same time points. The rate of positive CRP was decreased within the
      same period (p = 0.002); however, the trend of the changes in other laboratory
      parameters including MPV, platelet count and ESR values was not significant. The
      measurement of MPV value did not correlate with disease activity in RA patients
      within 4 months of treatment scheduling. Conclusion: Although therapeutic
      regimens, which improve RA manifestations, can reduce RA activity, they had no
      effect on MPV during this time period. It seems MPV may not be able to predict
      disease activity in RA patients.

PMID- 29187947
TI  - Macroprolactinemia and Empty Sella Syndrome.
AB  - Macroprolactinemia is a polymeric form of prolactin-release, causing mildly
      symptomatic clinical pictures. The former can be isolated or associated with
      other causes of hyperprolactinemia. The association with an empty sella syndrome
      is rare. We report a case of a female patient discovered with this association.
      It's about a female patient 47 years old, followed up since the age of 31 years
      for bilateral galactorrhea and a spaniomenorrhea. There has been no associated
      drug intake. Her exploration has showed a serum prolactin level of 635 mIU/L.
      Thyroid test results were normal T4 = 10,2ng/L and TSH = 1.76 mIU/L. A brain scan
      has showed an empty sella turcica. Despite the unchanged levels of prolactinemia,
      the evolution under dopaminergic 5 mg /D has been marked by the occurrence of a
      pregnancy with persistent moderate hyperprolactinemia in the postpartum.
      Chromatography has showed a predominance of the macroprolactin form with:
      Prolactin monomer at 4.8%, Big Prolactin at 5% and Big Big Prolactin at 83%, thus
      stopping bromocriptine. Our observation suggests that macroprolactinemia can be
      associated with conventional etiologies of moderate hyperprolactinemia as the
      empty sella syndrome. Its detection would prevent the use of dopaminergic therapy
      which seems not useful.

PMID- 29187948
TI  - Nutritional status, weight perception and weight control practices among office
      employees in Sokoto, Nigeria.
AB  - Introduction: Overweight and obesity have become the fifth leading risk for
      global deaths. Office employees have been identified as a high risk group due to
      the sedentary nature of their work, and accurate weight perception is believed to
      be critical to acceptance of weight control interventions. This study was
      conducted to assess the nutritional status, weight perception and weight control
      practices of office employees in Sokoto, Nigeria. Methods: A cross sectional
      study was conducted among 285 randomly selected office employees in private
      establishments in Sokoto, Nigeria, in February and March 2013. Anthropometry was
      done for the participants in addition to questionnaire administration. Results:
      The mean age of the participants was 33.08 +/- 7.23 years, they were
      predominantly males (56.5%) and married (57.5%). None was underweight, 111
      (38.9%) had normal weight, 105 (36.8%) were overweight and 69 (24.2%) were obese.
      Among the participants with normal weight, overweight and obesity, 71.2%, 35.2%
      and 58.0% respectively accurately perceived their weight; while 28.8%, 50.5% and
      30.4% respectively underestimated their weight. There was poor agreement between
      actual and perceived weight (k statistics = 0.341, p < 0.001). Only 67 (23.5%) of
      the 285 participants were engaged in weight control practices. Conclusion: This
      study showed high prevalence of overweight and obesity, weight misperceptions,
      and poor uptake of weight control practices among office employees in Sokoto,
      Nigeria. These findings underscore the need for a holistic approach to obesity
      control interventions that encompasses both body image perception and nutritional
      assessment.

PMID- 29187946
TI  - The endoscopic endonasal approach to cranio-cervical junction: the complete
      panel.
AB  - We aim to establish a complete summary on the Endoscopic Endonasal Approach (EEA)
      to Cranio Cervical Junction (CCJ): evolution since first description, criteria to
      predict the feasibility and limitations, anatomical landmarks, indications and
      biomechanical evaluation after performing the approach. A comprehensive
      literature search to identify all available literature published between March
      2002 and June 2015, the articles were divided into four categories according to
      their main purpose: 1- surgical technique, 2- anatomical landmarks and
      limitations, 3- literature reviews to identify main indications, 4- biomechanical
      studies. Thereafter, we demonstrate the approach step-by-step, using 1 fresh and
      3 silicon injected embalmed cadaveric specimen heads. 61 articles and one poster
      were identified. The approach was first described on cadaveric study in 2002, and
      firstly used to perform odontoidectomy in 2005. The main indication is odontoid
      rheumatoid pannus and basilar invagination. The nasopalatine line (NPL), the
      superior nostril-hard palate Line (SN-HP), the naso-axial line (NAxL), the
      rhinopalatine Line (RPL) and other methods were described to predict the
      anatomical feasibility of the approach. The craniocervical fusion is potentially
      unnecessary after removal of < 75% of one occipital condyle. A recent cadaveric
      study stated the possibility of C1-C2 fusion via EEA. This paper reviews all
      available clinical and anatomical studies on the EEA to CCJ. The approach marked
      a significant evolution since its first description in 2002. Because of its
      lesser complications compared to the transoral approach, the EEA became when
      feasible, the approach of choice to the ventral CCJ.

PMID- 29187949
TI  - Knowledge and perceptions of health and environmental risks related to artisanal
      gold mining by the artisanal miners in Burkina Faso: a cross-sectional survey.
AB  - Introduction: Artisanal gold mining is an activity ensuring the survival of about
      700,000 families in Burkina Faso with a considerable contribution to the national
      economy. Techniques and chemicals used in the operation, have adverse impacts on
      health and the environment. Our study aims to evaluate the perceptions and
      knowledge of these different impacts among artisanal gold miners. Methods: A
      cross-sectional survey was conducted in artisanal gold mines Bouda and Nagsene in
      the region of the North of Burkina Faso. Two hundred miners over 18 years of age
      were interviewed. Results: All the participants have recognized that gold mining
      has health impacts and 88.5% felt these impacts as important with a significantly
      higher proportion among those with more than 3 years' seniority (p = 0.001). The
      environmental impacts were perceived as important by 64.5% of miners, with a
      significant difference according to the position (p = 0.004). Sixty percent (60%)
      of respondents could identify at least 3 of the 5 health impacts of gold mining
      listed and 49.5% acknowledged at least 3 impacts on the environment. The diggers
      had significantly more knowledge about the symptoms (p < 0.001). Conclusion:
      Study highlights the lack of knowledge of the Stampeders on the health and
      environmental impacts of artisanal gold mining. Findings might be used to develop
      more effective awareness campaigns in the future. Communication with diggers must
      focus on the risk perception because it appears that raising risk perceptions
      from low to high would have a major effect on behavior.

PMID- 29187951
TI  - Profiling study of the major and minor components of kaffir lime oil (Citrus
      hystrix DC.) in the fractional distillation process.
AB  - Introduction: Essential oil is consisting of complex component. It is divided
      into major and minor component. Therefore, this study aims to examine the
      distribution of major and minor components on Kaffir lime oil by using fractional
      distillation. Fractional distillation and distributional analysis of components
      within fractions have been performed on kaffir lime oil (Citrus hystrix DC.).
      Methods: Fractional distillation was performed by using PiloDist 104-VTU, column
      length of 2 m (number of plate 120), the system pressure was set on 5 and 10
      mBar, while the reflux ratio varied on 10/10, 20/10 and 60/10, and the chemical
      composition analysis was done by using GC-MS. Chemical composition of the
      distillated lime oil consisted of mix-twigs and leaves that composed of 20
      compounds, with five main components beta-citronellal (46.40%), L-linalool
      (13.11%), beta-citronellol (11.03%), citronelyl acetate (6.76%) and sabinen
      (5.91%). Results: The optimum conditions for fractional distillation were
      obtained at 5 mBar pressure with reflux ratio of 10/10. Components of beta 
      citronellal and L-linalool were distributed in the fraction-1 to fraction 9,
      hydrocarbon monoterpenes components were distributed only on the fraction-1 to
      fraction 4, while the oxygenated monoterpenes components dominated the fraction-5
      to fraction-9. Conclusion: The highest level of beta-citronellal was 84.86%
      (fraction-7), L-linalool 20.13% (fraction-5), sabinen 19.83% (fraction-1), and
      the component level of 4-terpeneol, beta-citronellol and sitronelyl acetate
      respectively 7.16%; 12.27%; 5.22% (fraction-9).

PMID- 29187950
TI  - Assessment of methicillin resistant Staphylococcus Aureus detection methods:
      analytical comparative study.
AB  - Introduction: The heterogeneous expression of methicillin resistance in
      Staphylococcus aureus (MRSA) affects the efficiency of tests available to detect
      it. The objective of this study was to assess four phenotypic tests used to
      detect MRSA. Methods: This is an analytical comparative study conducted among
      sudanese patients during period from May 2012 to July 2014, Staphylococcus aureus
      strains were isolated and identified by conventional methods, and then confirmed
      by PCR detection of coagulase gene. PCR detection of mecA gene was used as a gold
      standard to assess oxacillin resistance screen agar base (ORSAB), oxacillin disc,
      cefoxitin disc (at different temperatures and incubation periods) and MRSA-latex
      agglutination test. S.aureus ATCC 25923 was used as control. Sensitivity and
      specificity were calculated. Results: MRSA- latex agglutination was the most
      accurate test; it showed 100% of both sensitivity and specificity, followed by
      cefoxitin disc with sensitivity of 98.48% and specificity of 100%. However, both
      of oxacillin disc and oxacillin resistance screen agar base showed less accurate
      results, and were affected by incubation periods. Oxacillin disc after 24 h
      incubation both at 30 degrees C and 35 degrees C showed sensitivity and
      specificity values of 87.88% and 96.23%, respectively. However, after 48h
      incubation the test at 30 degrees C showed sensitivity and specificity values of
      89.39%, and 94.34%, respectively. At 35 degrees C (48h) it showed values of
      89.39%, 92.45% respectively. Specificity of ORSAB was more than oxacillin disc at
      35 degrees C after 24h incubation 98.11% and 96.23%, respectively. Conclusion:
      MRSA- latex agglutination and cefoxitin disc diffusion tests are recommended for
      routine detection of MRSA.

PMID- 29187952
TI  - Solid pseudopapillary neoplasm of the pancreas in two male patients: gender does
      not matter.
AB  - Solid pseudopapillary tumour (SPT) is an unusual pancreatic neoplasm which
      predominantly affects young women. Less than 10% of patients with SPT in the
      reported literature were male. In this paper, the authors report two new cases of
      SPT that occurred in two male patients aged respectively 25 and 20 years old.
      Abdominal computed tomography scan showed a well-defined heterogeneous mass
      involving respectively the tail and the body of the pancreas with peripheral
      calcifications in the first case. The two patients underwent distal
      splenopancreatectomy. Histopathological examination of the surgical specimen
      coupled with immunohistochemical study was compatible with solid pseudopapillary
      tumour. On postoperative day 8, the first patient developed abdominal wall
      abscess and peritoneal collection. Postoperative course was uneventful for the
      second patient. In summary, a large, well-encapsulated cystic mass in the
      pancreas of a young man should raise suspicion of solid pseudopapillary tumour.

PMID- 29187953
TI  - Seasonal distribution and faunistic of ticks in the Alashtar county (Lorestan
      Province), Iran.
AB  - Introduction: Ticks are non-permanent obligate parasites that have considerable
      medical-veterinary and zoonosis importance. In this regard a study designed to
      investigate the distribution and fauna of ticks in the Alashtar county in Iran
      from April and March 2014. Methods: Ticks were collected from livestock farms and
      facilities from selected rural and geographically location in the Alashtar
      county. Based morphological characteristics and reference identification keys,
      ticks were identified. Results: A total of 549 ticks including 411 hard and 138
      soft ticks were found. Ten tick species including Haemaphysalis concinna (0.36%),
      Haemaphysalis sulcata (0.36%), Hyalomma anatolicum (0.18%), Hyalomma dromedarii
      (0.18%), Hyalomma marginatum (1.45 %), Hyalomma schulzei (0.36%), Rhipicephalus
      annulatus (0.18%), Rhipicephalus bursa (28.1%), Rhipicephalus sanguineus (43.63%)
      and Argas persicus (25.2%) were identified. Tick seasonal distribution were
      47.26%, 22.63%, 14.96% and 15.15% in the spring, summer, autumn and winter,
      respectively. The tick distribution was more from plain areas (64.96%) than the
      mountainous areas (35.04%). The rates of the tick contamination were 97.3% and
      2.7% in the traditional and industrial livestock's, respectively. The livestock
      contamination ranks to the hard ticks were cattle (39.51%), sheep (34.15%) and
      goats (26.34 %), respectively. Chi-square analysis showed a significant
      difference among the seasonal distribution of the ticks in the spring, summer and
      autumn or winter; between the tick distribution in the plain and mountainous
      areas; and between the traditional and industrial livestock's tick contamination
      (P < 0.05). Conclusion: Present study proves to change the traditional
      livestock's to the industrial livestock's. These findings highlight the
      importance of ticks and shows need to their control and tick pest management.

PMID- 29187955
TI  - Duodenal diverticulitis: a difficult clinical problem.

PMID- 29187954
TI  - Application of psychosocial models to Home-Based Testing and Counseling (HBTC)
      for increased uptake and household coverage in a large informal urban settlement
      in Kenya.
AB  - Introduction: Home Based Testing and Counselling (HBTC) aims at reaching
      individuals who have low HIV risk perception and experience barriers which
      prevent them from seeking HIV testing and counseling (HTC) services. Saturating
      the community with HTC is needed to achieve the ambitious 90-90-90 targets of
      knowledge of HIV status, ARV treatment and viral suppression. This paper
      describes the use of health belief model and community participation principles
      in HBTC to achieve increased household coverage and HTC uptake. Methods: This
      cross sectional survey was done between August 2009 and April 2011 in Kibera
      slums, Nairobi city. Using three community participation principles; defining and
      mobilizing the community, involving the community, overcoming barriers and
      respect to cultural differences and four constructs of the health belief model;
      risk perception, perceived severity, perceived benefits of changed behavior and
      perceived barriers; we offered HTC services to the participants. Descriptive
      statistics were used to describe socio-demographic characteristics, calculate
      uptake and HIV prevalence. Results: There were 72,577 individuals enumerated at
      the start of the program; 75,141 residents were found during service delivery. Of
      those, 71,925 (95.7%) consented to participate, out of which 71,720 (99.7%) took
      the HIV test. First time testers were (39%). The HIV prevalence was higher (6.4%)
      among repeat testers than first time testers (4.0%) with more women (7.4%)
      testing positive than men (3.6%) and an overall 5.5% slum prevalence. Conclusion:
      This methodology demonstrates that the use of community participation principles
      combined with a psychosocial model achieved high HTC uptake, coverage and
      diagnosed HIV in individuals who believed they are HIV free. This novel approach
      provides baseline for measuring HTC coverage in a community.

PMID- 29187956
TI  - [Leg ulcer revealing cutaneous leishmaniasis].
AB  - Leishmaniases are parasitic diseases occurring in endemic tropical and
      subtropical areas and caused by protozoa of the genus leishmania, transmitted by
      a diptera (sand fly). We here report a case of topical cutaneous leishmaniasis
      discovered in a 15-year old boy with painless ulcer on his left leg, who had been
      staying in South Africa. Clinical examination showed painless non-itchy ulcer,
      occurred 1 month before, on the antero-internal part of his left leg with crusts
      and scars caused by insect bites, all evolving in a context of patient's general
      health status, without mucosal or visceral lesions. Skin biopsy allowed specific
      parasitologic diagnosis revealing topical zoonotic cutaneous leishmaniasis caused
      by L. major. The patient underwent topical treatment based on paramomycin and
      oral fluconazole resulting in ulcer healing at the end of 2 months.

PMID- 29187957
TI  - Cricopharyngeal bar.

PMID- 29187958
TI  - Giving the Underdog a Leg Up: A Counternarrative of Nonviolent Resistance
      Improves Sustained Third-Party Support of a Disempowered Group.
AB  - In the current work, we experimentally examined the effect of exposure to a
      narrative of nonviolent resistance on third-party attitudes toward and support
      for a disempowered group involved in asymmetric conflict. Across three
      experiments, we found that Americans exposed to a brief video about Palestinian
      nonviolent resistance consistently registered more favorable attitudes toward
      Palestinians than people who watched a film trailer either unrelated to the
      Israeli-Palestinian conflict or a trailer to a Palestinian-made film about
      sympathetic Palestinians violently opposing Israelis. Americans' attitudes toward
      Palestinians and behavior supporting Palestinian collective action persisted
      weeks after exposure to nonviolent resistance and were mediated by decreased
      perceptions that Palestinians are inherently violent. Importantly, positive
      attitudes toward Palestinians did not result in increased negativity toward
      Israelis. These data show that exposure to nonviolent resistance can have lasting
      effects on third-party attitudes and behavior toward an underdog/disempowered
      group, without driving partisanship.

PMID- 29187959
TI  - Frankly, We Do Give a Damn: The Relationship Between Profanity and Honesty.
AB  - There are two conflicting perspectives regarding the relationship between
      profanity and dishonesty. These two forms of norm-violating behavior share common
      causes and are often considered to be positively related. On the other hand,
      however, profanity is often used to express one's genuine feelings and could
      therefore be negatively related to dishonesty. In three studies, we explored the
      relationship between profanity and honesty. We examined profanity and honesty
      first with profanity behavior and lying on a scale in the lab (Study 1; N = 276),
      then with a linguistic analysis of real-life social interactions on Facebook
      (Study 2; N = 73,789), and finally with profanity and integrity indexes for the
      aggregate level of U.S. states (Study 3; N = 50 states). We found a consistent
      positive relationship between profanity and honesty; profanity was associated
      with less lying and deception at the individual level and with higher integrity
      at the society level.

PMID- 29187960
TI  - Meta-analysis of Liver and Heart Transcriptomic Data for Functional Annotation
      Transfer in Mammalian Orthologs.
AB  - Functional annotation transfer across multi-gene family orthologs can lead to
      functional misannotations. We hypothesised that co-expression network will help
      predict functional orthologs amongst complex homologous gene families. To explore
      the use of transcriptomic data available in public domain to identify
      functionally equivalent ones from all predicted orthologs, we collected genome
      wide expression data in mouse and rat liver from over 1500 experiments with
      varied treatments. We used a hyper-graph clustering method to identify clusters
      of orthologous genes co-expressed in both mouse and rat. We validated these
      clusters by analysing expression profiles in each species separately, and
      demonstrating a high overlap. We then focused on genes in 18 homology groups with
      one-to-many or many-to-many relationships between two species, to discriminate
      between functionally equivalent and non-equivalent orthologs. Finally, we further
      applied our method by collecting heart transcriptomic data (over 1400
      experiments) in rat and mouse to validate the method in an independent tissue.

PMID- 29187961
TI  - Host size influences the effects of four isolates of an amphibian chytrid fungus.
AB  - Understanding factors that influence host-pathogen interactions is key to
      predicting outbreaks in natural systems experiencing environmental change. Many
      amphibian population declines have been attributed to an amphibian chytrid
      fungus, Batrachochytrium dendrobatidis (Bd). While this fungus is widespread, not
      all Bd-positive populations have been associated with declines, which could be
      attributed to differences in pathogen virulence or host susceptibility. In a
      laboratory experiment, we examined the effects of Bd isolate origin, two from
      areas with Bd-associated amphibian population declines (El Cope, Panama, and
      California, USA) and two from areas without Bd-related population declines (Ohio
      and Maine, USA), on the terrestrial growth and survival of American toad
      (Anaxyrus americanus) metamorphs reared in larval environments with low or high
      intraspecific density. We predicted that (1) Bd isolates from areas experiencing
      declines would have greater negative effects than Bd isolates from areas without
      declines, and (2) across all isolates, growth and survival of smaller toads from
      high-density larval conditions would be reduced by Bd exposure compared to larger
      toads from low-density larval conditions. Our results showed that terrestrial
      survival was reduced for smaller toads exposed to Bd with variation in the
      response to different isolates, suggesting that smaller size increased
      susceptibility to Bd. Toads exposed to Bd gained less mass, which varied by
      isolate. Bd isolates from areas with population declines, however, did not have
      more negative effects than isolates from areas without recorded declines. Most
      strikingly, our study supports that host condition, measured by size, can be
      indicative of the negative effects of Bd exposure. Further, Bd isolates' impact
      may vary in ways not predictable from place of origin or occurrence of disease
      related population declines. This research suggests that amphibian populations
      outside of areas experiencing Bd-associated declines could be impacted by this
      pathogen and that the size of individuals could influence the magnitude of Bd's
      impact.

PMID- 29187962
TI  - Landscape-scale genetic differentiation of a mycangial fungus associated with the
      ambrosia beetle, Xylosandrus germanus (Blandford) (Curculionidae:Scolytinae) in
      Japan.
AB  - In this study, we examined the genetic structures of the ambrosia fungus isolated
      from mycangia of the scolytine beetle, Xylosandrus germanus to understand their
      co-evolutionary relationships. We analyzed datasets of three ambrosia fungus loci
      (18S rDNA, 28S rDNA, and the beta-tubulin gene) and a X. germanus locus dataset
      (cytochrome c oxidase subunit 1 (COI) mitochondrial DNA). The ambrosia fungi were
      separated into three cultural morphptypes, and their haplotypes were
      distinguished by phylogenetic analysis on the basis of the three loci. The COI
      phylogenetic analysis revealed three distinct genetic lineages (clades A, B, and
      C) within X. germanus, each of which corresponded to specific ambrosia fungus
      cultural morphptypes. The fungal symbiont phylogeny was not concordant with that
      of the beetle. Our results suggest that X. germanus may be unable to exchange its
      mycangial fungi, but extraordinary horizontal transmission of symbiotic fungi
      between the beetle's lineages occurred at least once during the evolutionary
      history of this symbiosis.

PMID- 29187963
TI  - Environmental correlates of internal coloration in frogs vary throughout space
      and lineages.
AB  - Internal organs of ectotherms have melanin-containing cells that confer different
      degrees of coloration to them. Previous experimental studies analyzed their
      developmental origin, role in immunity, and hormonal regulation. For example,
      melanin increases with ultraviolet radiation (UV) and temperature in frogs and
      fish. However, little is known about how environmental variables influence the
      amount of coloration on organs among amphibian species over a large spatial
      extent. Here, we tested how climatic variables (temperature, UV, and photoperiod)
      influence the coloration of internal organs of anurans. We recorded the level of
      melanin pigmentation using four categories on 12 internal organs and structures
      of 388 specimens from 43 species belonging to six anuran families. Then, we
      tested which climatic variables had the highest covariation with the pigmentation
      on each organ after controlling for spatial autocorrelation in climatic variables
      and phylogenetic signal in organ coloration using the extended version of the RLQ
      ordination. Coloration in all organs was correlated with the phylogeny. However,
      the coloration of different organs was affected by different variables.
      Specifically, the coloration of the heart, kidneys, and rectum of hylids,
      Rhinella schneideri, some Leptodactylus, and Proceratophrys strongly covaried
      with temperature and photoperiod, whereas that of the testicle, lumbar parietal
      peritoneum, lungs, and mesenterium of Leiuperinae, Hylodidae, Adenomera, and most
      Leptodactylus had highest covariation with UV-B and temperature. Our results
      support the notion that melanin pigmentation on the surface of organs of
      amphibians has an adaptive function conferred by the protective functions of the
      pigment. But most importantly, internal melanin seems to respond differently to
      climatic variables depending on the lineage and locality in which species occur.

PMID- 29187964
TI  - Population structure and connectivity of the mountainous star coral, Orbicella
      faveolata, throughout the wider Caribbean region.
AB  - As coral reefs continue to decline worldwide, it becomes ever more necessary to
      understand the connectivity between coral populations to develop efficient
      management strategies facilitating survival and adaptation of coral reefs in the
      future. Orbicella faveolata is one of the most important reef-building corals in
      the Caribbean and has recently experienced severe population reductions. Here, we
      utilize a panel of nine microsatellite loci to evaluate the genetic structure of
      O. faveolata and to infer connectivity across ten sites spanning the wider
      Caribbean region. Populations are generally well-mixed throughout the basin (FST
      = 0.038), although notable patterns of substructure arise at local and regional
      scales. Eastern and western populations appear segregated with a genetic break
      around the Mona Passage in the north, as has been shown previously in other
      species; however, we find evidence for significant connectivity between Curacao
      and Mexico, suggesting that the southern margin of this barrier is permeable to
      dispersal. Our results also identify a strong genetic break within the
      Mesoamerican Barrier Reef System associated with complex oceanographic patterns
      that promote larval retention in southern Belize. Additionally, the diverse
      genetic signature at Flower Garden Banks suggests its possible function as a
      downstream genetic sink. The findings reported here are relevant to the ongoing
      conservation efforts for this important and threatened species, and contribute to
      the growing understanding of large-scale coral reef connectivity throughout the
      wider Caribbean.

PMID- 29187965
TI  - The role of species-specific sensory cues in male responses to mating rivals in
      Drosophila melanogaster fruitflies.
AB  - Complex sets of cues can be important in recognizing and responding to
      conspecific mating competitors and avoiding potentially costly heterospecific
      competitive interactions. Within Drosophila melanogaster, males can detect
      sensory inputs from conspecifics to assess the level of competition. They respond
      to rivals by significantly extending mating duration and gain significant fitness
      benefits from doing so. Here, we tested the idea that the multiple sensory cues
      used by D. melanogaster males to detect conspecifics also function to minimize
      "off-target" responses to heterospecific males that they might encounter
      (Drosophila simulans, Drosophila yakuba, Drosophila pseudoobscura, or Drosophila
      virilis). Focal D. melanogaster males exposed to D. simulans or D. pseudoobscura
      subsequently increased mating duration, but to a lesser extent than following
      exposure to conspecific rivals. The magnitude of rivals' responses expressed by
      D. melanogaster males did not align with genetic distance between species, and
      none of the sensory manipulations caused D. melanogaster to respond to males of
      all other species tested. However, when we removed or provided "false" sensory
      cues, D. melanogaster males became more likely to show increased mating duration
      responses to heterospecific males. We suggest that benefits of avoiding
      inaccurate assessment of the competitive environment may shape the evolution of
      recognition cues.

PMID- 29187966
TI  - Changing measurements or changing movements? Sampling scale and movement model
      identifiability across generations of biologging technology.
AB  - Animal movement patterns contribute to our understanding of variation in breeding
      success and survival of individuals, and the implications for population
      dynamics. Over time, sensor technology for measuring movement patterns has
      improved. Although older technologies may be rendered obsolete, the existing data
      are still valuable, especially if new and old data can be compared to test
      whether a behavior has changed over time. We used simulated data to assess the
      ability to quantify and correctly identify patterns of seabird flight lengths
      under observational regimes used in successive generations of wet/dry logging
      technology. Care must be taken when comparing data collected at differing
      timescales, even when using inference procedures that incorporate the
      observational process, as model selection and parameter estimation may be biased.
      In practice, comparisons may only be valid when degrading all data to match the
      lowest resolution in a set. Changes in tracking technology, such as the wet/dry
      loggers explored here, that lead to aggregation of measurements at different
      temporal scales make comparisons challenging. We therefore urge ecologists to use
      synthetic data to assess whether accurate parameter estimation is possible for
      models comparing disparate data sets before planning experiments and conducting
      analyses such as responses to environmental changes or the assessment of
      management actions.

PMID- 29187967
TI  - Highly contrasted population genetic structures in a host-parasite pair in the
      Caribbean Sea.
AB  - Evolution and population genetic structure of marine species across the Caribbean
      Sea are shaped by two complex factors: the geological history and the present
      pattern of marine currents. Characterizing and comparing the genetic structures
      of codistributed species, such as host-parasite associations, allow
      discriminating the relative importance of environmental factors and life history
      traits that influenced gene flow and demographic events. Using microsatellite and
      Cytochrome Oxidase I markers, we investigated if a host-parasite pair (the heart
      urchin Meoma ventricosa and its parasitic pea crab Dissodactylus primitivus)
      exhibits comparable population genetic structures in the Caribbean Sea and how
      the observed patterns match connectivity regions from predictive models and other
      taxa. Highly contrasting patterns were found: the host showed genetic homogeneity
      across the whole studied area, whereas the parasite displayed significant
      differentiation at regional and local scales. The genetic diversity of the
      parasitic crabs (both in microsatellites and COI) was distributed in two main
      groups, Panama-Jamaica-St Croix on the one hand, and the South-Eastern Caribbean
      on the other. At a smaller geographical scale, Panamanian and Jamaican parasite
      populations were genetically more similar, while more genetic differentiation was
      found within the Lesser Antilles. Both species showed a signature of population
      expansion during the Quaternary. Some results match predictive models or data
      from previous studies (e.g., the Western-Eastern dichotomy in the parasite) while
      others do not (e.g., genetic differentiation within the Lesser Antilles). The
      sharp dissimilarity of genetic structure of these codistributed species outlines
      the importance of population expansion events and/or contrasted patterns of gene
      flow. This might be linked to differences in several life history traits such as
      fecundity (higher for the host), swimming capacity of larval stages (higher for
      the parasite), and habitat availability (higher for the host).

PMID- 29187968
TI  - The xeric side of the Brazilian Atlantic Forest: The forces shaping
      phylogeographic structure of cacti.
AB  - In order to investigate biogeographic influences on xeric biota in the Brazilian
      Atlantic Forest (BAF), a biodiversity hotspot, we used a monophyletic group
      including three cactus taxa as a model to perform a phylogeographic study: Cereus
      fernambucensis subsp. fernambucensis, C. fernambucensis subsp. sericifer, and C.
      insularis. These cacti are allopatric and grow in xeric habitats along BAF,
      including isolated granite and gneiss rock outcrops (Inselbergs), sand dune
      vegetation (Restinga forest), and the rocky shore of an oceanic archipelago
      (islands of Fernando de Noronha). The nucleotide information from nuclear gene
      phytochrome C and plastid intergenic spacer trnS-trnG was used to perform
      different approaches and statistical analyses, comprising population structure,
      demographic changes, phylogenetic relationships, and biogeographic reconstruction
      in both spatial and temporal scales. We recovered four allopatric population
      groups with highly supported branches in the phylogenetic tree with divergence
      initiated in the middle Pleistocene: southern distribution of C. fernambucensis
      subsp. fernambucensis, northern distribution of C. fernambucensis subsp.
      fernambucensis together with C. insularis, southern distribution of C.
      fernambucensis subsp. sericifer, and northern distribution of C. fernambucensis
      subsp. sericifer. Further, the results suggest that genetic diversity of
      population groups was strongly shaped by an initial colonization event from south
      to north followed by fragmentation. The phylogenetic pattern found for C.
      insularis is plausible with peripatric speciation in the archipelago of Fernando
      de Noronha. To explain the phylogeographic patterns, the putative effects of both
      climatic and sea level changes as well as neotectonic activity during the
      Pleistocene are discussed.

PMID- 29187969
TI  - Syntopic frogs reveal different patterns of interaction with the landscape: A
      comparative landscape genetic study of Pelophylax nigromaculatus and Fejervarya
      limnocharis from central China.
AB  - Amphibians are often considered excellent environmental indicator species.
      Natural and man-made landscape features are known to form effective genetic
      barriers to amphibian populations; however, amphibians with different
      characteristics may have different species-landscape interaction patterns. We
      conducted a comparative landscape genetic analysis of two closely related
      syntopic frog species from central China, Pelophylax nigromaculatus (PN) and
      Fejervarya limnocharis (FL). These two species differ in several key life history
      traits; PN has a larger body size and larger clutch size, and reaches sexual
      maturity later than FL. Microsatellite DNA data were collected and analyzed using
      conventional (FST, isolation by distance (IBD), AMOVA) and recently developed
      (Bayesian assignment test, isolation by resistance) landscape genetic methods. As
      predicted, a higher level of population structure in FL (FST' = 0.401) than in PN
      (FST' = 0.354) was detected, in addition to FL displaying strong IBD patterns (r
      = .861) unlike PN (r = .073). A general north-south break in FL populations was
      detected, consistent with the IBD pattern, while PN exhibited clustering of
      northern- and southern-most populations, suggestive of altered dispersal
      patterns. Species-specific resistant landscape features were also identified,
      with roads and land cover the main cause of resistance to FL, and elevation the
      main influence on PN. These different species-landscape interactions can be
      explained mostly by their life history traits, revealing that closely related and
      ecologically similar species have different responses to the same landscape
      features. Comparative landscape genetic studies are important in detecting such
      differences and refining generalizations about amphibians in monitoring
      environmental changes.

PMID- 29187970
TI  - Land use not litter quality is a stronger driver of decomposition in hyperdiverse
      tropical forest.
AB  - In hyperdiverse tropical forests, the key drivers of litter decomposition are
      poorly understood despite its crucial role in facilitating nutrient availability
      for plants and microbes. Selective logging is a pressing land use with potential
      for considerable impacts on plant-soil interactions, litter decomposition, and
      nutrient cycling. Here, in Borneo's tropical rainforests, we test the hypothesis
      that decomposition is driven by litter quality and that there is a significant
      "home-field advantage," that is positive interaction between local litter quality
      and land use. We determined mass loss of leaf litter, collected from selectively
      logged and old-growth forest, in a fully factorial experimental design, using
      meshes that either allowed or precluded access by mesofauna. We measured leaf
      litter chemical composition before and after the experiment. Key soil chemical
      and biological properties and microclimatic conditions were measured as land-use
      descriptors. We found that despite substantial differences in litter quality, the
      main driver of decomposition was land-use type. Whilst inclusion of mesofauna
      accelerated decomposition, their effect was independent of land use and litter
      quality. Decomposition of all litters was slower in selectively logged forest
      than in old-growth forest. However, there was significantly greater loss of
      nutrients from litter, especially phosphorus, in selectively logged forest. The
      analyses of several covariates detected minor microclimatic differences between
      land-use types but no alterations in soil chemical properties or free-living
      microbial composition. These results demonstrate that selective logging can
      significantly reduce litter decomposition in tropical rainforest with no evidence
      of a home-field advantage. We show that loss of key limiting nutrients from
      litter (P & N) is greater in selectively logged forest. Overall, the findings
      hint at subtle differences in microclimate overriding litter quality that result
      in reduced decomposition rates in selectively logged forests and potentially
      affect biogeochemical nutrient cycling in the long term.

PMID- 29187971
TI  - Plant diversity has contrasting effects on herbivore and parasitoid abundance in
      Centaurea jacea flower heads.
AB  - High biodiversity is known to increase many ecosystem functions, but studies
      investigating biodiversity effects have more rarely looked at multi-trophic
      interactions. We studied a tri-trophic system composed of Centaurea jacea (brown
      knapweed), its flower head-infesting tephritid fruit flies and their hymenopteran
      parasitoids, in a grassland biodiversity experiment. We aimed to disentangle the
      importance of direct effects of plant diversity (through changes in apparency and
      resource availability) from indirect effects (mediated by host plant quality and
      performance). To do this, we compared insect communities in C. jacea transplants,
      whose growth was influenced by the surrounding plant communities (and where
      direct and indirect effects can occur), with potted C. jacea plants, which do not
      compete with the surrounding plant community (and where only direct effects are
      possible). Tephritid infestation rate and insect load, mainly of the dominant
      species Chaetorellia jaceae, decreased with increasing plant species and
      functional group richness. These effects were not seen in the potted plants and
      are therefore likely to be mediated by changes in host plant performance and
      quality. Parasitism rates, mainly of the abundant chalcid wasps Eurytoma
      compressa and Pteromalus albipennis, increased with plant species or functional
      group richness in both transplants and potted plants, suggesting that direct
      effects of plant diversity are most important. The differential effects in
      transplants and potted plants emphasize the importance of plant-mediated direct
      and indirect effects for trophic interactions at the community level. The
      findings also show how plant-plant interactions critically affect results
      obtained using transplants. More generally, our results indicate that plant
      biodiversity affects the abundance of higher trophic levels through a variety of
      different mechanisms.

PMID- 29187972
TI  - Interactive effects of temperature and habitat complexity on freshwater
      communities.
AB  - Warming can lead to increased growth of plants or algae at the base of the food
      web, which may increase the overall complexity of habitat available for other
      organisms. Temperature and habitat complexity have both been shown to alter the
      structure and functioning of communities, but they may also have interactive
      effects, for example, if the shade provided by additional habitat negates the
      positive effect of temperature on understory plant or algal growth. This study
      explored the interactive effects of these two major environmental factors in a
      manipulative field experiment, by assessing changes in ecosystem functioning
      (primary production and decomposition) and community structure in the presence
      and absence of artificial plants along a natural stream temperature gradient of 5
      18 degrees C. There was no effect of temperature or habitat complexity on benthic
      primary production, but epiphytic production increased with temperature in the
      more complex habitat. Cellulose decomposition rate increased with temperature,
      but was unaffected by habitat complexity. Macroinvertebrate communities were less
      similar to each other as temperature increased, while habitat complexity only
      altered community composition in the coldest streams. There was also an overall
      increase in macroinvertebrate abundance, body mass, and biomass in the warmest
      streams, driven by increasing dominance of snails and blackfly larvae. Presence
      of habitat complexity, however, dampened the strength of this temperature effect
      on the abundance of macroinvertebrates in the benthos. The interactive effects
      that were observed suggest that habitat complexity can modify the effects of
      temperature on important ecosystem functions and community structure, which may
      alter energy flow through the food web. Given that warming is likely to increase
      habitat complexity, particularly at higher latitudes, more studies should
      investigate these two major environmental factors in combination to improve our
      ability to predict the impacts of future global change.

PMID- 29187973
TI  - Variation in reproductive isolation across a species range.
AB  - Reproductive isolation is often variable within species, a phenomenon that while
      largely ignored by speciation studies, can be leveraged to gain insight into the
      potential mechanisms driving the evolution of genetic incompatibilities. We used
      experimental greenhouse crosses to characterize patterns of reproductive
      isolation among three divergent genetic lineages of Campanulastrum americanum
      that occur in close geographic proximity in the Appalachian Mountains.
      Substantial, asymmetrical reproductive isolation for survival due to cytonuclear
      incompatibility was found among the lineages (up to 94% reduction). Moderate
      reductions in pollen viability, as well as cytoplasmic male sterility, were also
      found between some Mountain populations. We then compared these results to
      previously established patterns of reproductive isolation between these Mountain
      lineages and a fourth, widespread Western lineage to fully characterize
      reproductive isolation across the complete geographic and genetic range of C.
      americanum. Reproductive isolation for survival and pollen viability was
      consistent across studies, indicating the evolution of the underlying genetic
      incompatibilities is primarily determined by intrinsic factors. In contrast,
      reproductive isolation for germination was only found when crossing Mountain
      populations with the Western lineage, suggesting the underlying genetic
      incompatibility is likely influenced by environmental or demographic differences
      between the two lineages. Cytoplasmic male sterility was also limited in
      occurrence, being restricted to a handful of Mountain populations in a narrow
      geographic range. These findings illustrate the complexity of speciation by
      demonstrating multiple, independent genetic incompatibilities that lead to a
      mosaic of genetic divergence and reproductive isolation across a species range.

PMID- 29187974
TI  - Likelihood of changes in forest species suitability, distribution, and diversity
      under future climate: The case of Southern Europe.
AB  - Forest conservation strategies and plans can be unsuccessful if the new habitat
      conditions determined by climate change are not considered. Our work aims at
      investigating the likelihood of future suitability, distribution and diversity
      for some common European forest species under the projected changes in climate,
      focusing on Southern Europe. We combine an Ensemble Platform for Species
      Distribution Models (SDMs) to five Global Circulation Models (GCMs) driven by two
      Representative Concentration Pathways (RCPs), to produce maps of future climate
      driven habitat suitability for ten categories of forest species and two time
      horizons. For each forest category and time horizon, ten maps of future
      distribution (5 GCMs by 2 RCPs) are thus combined in a single suitability map
      supplied with information about the "likelihood" adopting the IPCC terminology
      based on consensus among projections. Then, the statistical significance of
      spatially aggregated changes in forest composition at local and regional level is
      analyzed. Finally, we discuss the importance, among SDMs, that environmental
      predictors seem to have in influencing forest distribution. Future impacts of
      climate change appear to be diversified across forest categories. A strong change
      in forest regional distribution and local diversity is projected to take place,
      as some forest categories will find more suitable conditions in previously
      unsuitable locations, while for other categories the same new conditions will
      become less suited. A decrease in species diversity is projected in most of the
      area, with Alpine region showing the potentiality to become a refuge for species
      migration.

PMID- 29187975
TI  - Evolutionary structure of Plasmodium falciparum major variant surface antigen
      genes in South America: Implications for epidemic transmission and surveillance.
AB  - Strong founder effects resulting from human migration out of Africa have led to
      geographic variation in single nucleotide polymorphisms (SNPs) and
      microsatellites (MS) of the malaria parasite, Plasmodium falciparum. This is
      particularly striking in South America where two major founder populations of P.
      falciparum have been identified that are presumed to have arisen from the
      transatlantic slave trade. Given the importance of the major variant surface
      antigen of the blood stages of P. falciparum as both a virulence factor and
      target of immunity, we decided to investigate the population genetics of the
      genes encoding "Plasmodium falciparum Erythrocyte Membrane Protein 1" (Pf EMP1)
      among several countries in South America, in order to evaluate the transmission
      patterns of malaria in this continent. Deep sequencing of the DBLalpha domain of
      var genes from 128 P. falciparum isolates from five locations in South America
      was completed using a 454 high throughput sequencing protocol. Striking
      geographic variation in var DBLalpha sequences, similar to that seen for SNPs and
      MS markers, was observed. Colombia and French Guiana had distinct var DBLalpha
      sequences, whereas Peru and Venezuela showed an admixture. The importance of such
      geographic variation to herd immunity and malaria vaccination is discussed.

PMID- 29187977
TI  - Impacts of environmental factors on the climbing behaviors of herbaceous stem
      twiners.
AB  - The curvature of the helical trajectory formed by herbaceous stem-twiners has
      been hypothesized to be constant on uniformly sized cylindrical supports and
      remains constant on different supports varying in diameter. However, experimental
      studies on the constant curvature hypothesis have been very limited. Here, we
      tested the hypothesis in a series of experiments on five herbaceous stem-twiners
      (Ipomoea triloba, Ipomoea nil, Phaseolus vulgaris, Vigna unguiculata, and Mikania
      micrantha). We investigated how internode characteristics (curvature [beta],
      diameter [d], and length [L]) and success rate (SR) of twining shoots would be
      affected by support thickness (D), temperature (T), illumination, and support
      inclination. The results showed that: (1) the SR of tested species decreased, but
      d increased with increasing support thickness. The beta of the twining shoots on
      erect cylindrical poles was not constant, but it decreased with increasing d or
      support thickness. (2) The SR of tested species was not obviously reduced under
      low-temperature conditions, but their beta was significantly higher and d
      significantly lower when temperature was more than 5 degrees C lower. (3) The SR
      , d, and L of two tested Ipomoea species significantly declined, but beta
      increased under 50% shading stress. (4) The curvatures of upper semicycles of I.
      triloba shoots on 45 degrees  inclined supports were not significantly different
      from curvatures of those shoots climb on erect supports, whereas the curvatures
      of lower semicycles were 40%-72% higher than curvatures of upper semicycles.
      Synthesis: Our study illustrates that stem curvatures of a certain herbaceous
      stem-twiners are not constant, but rather vary in response to external support,
      temperature, and illumination conditions. We speculate that herbaceous stem
      twiners positively adapt to wide-diameter supports by thickening their stems and
      by reducing their twining curvatures. This insight helps us better understand
      climbing processes and dynamics of stem-twiners in forest communities and
      ecosystems.

PMID- 29187978
TI  - Incubation behavior adjustments, driven by ambient temperature variation, improve
      synchrony between hatch dates and caterpillar peak in a wild bird population.
AB  - For organisms living in seasonal environments, synchronizing the peak energetic
      demands of reproduction with peak food availability is a key challenge.
      Understanding the extent to which animals can adjust behavior to optimize
      reproductive timing, and the cues they use to do this, is essential for
      predicting how they will respond to future climate change. In birds, the timing
      of peak energetic demand is largely determined by the timing of clutch
      initiation; however, considerable alterations can still occur once egg laying has
      begun. Here, we use a wild population of great tits (Parus major) to quantify
      individual variation in different aspects of incubation behavior (onset,
      duration, and daily intensity) and conduct a comprehensive assessment of the
      causes and consequences of this variation. Using a 54-year dataset, we
      demonstrate that timing of hatching relative to peak prey abundance (synchrony)
      is a better predictor of reproductive success than clutch initiation or clutch
      completion timing, suggesting adjustments to reproductive timing via incubation
      are adaptive in this species. Using detailed in-nest temperature recordings, we
      found that postlaying, birds improved their synchrony with the food peak
      primarily by varying the onset of incubation, with duration changes playing a
      lesser role. We then used a sliding time window approach to explore which spring
      temperature cues best predict variance in each aspect of incubation behavior.
      Variation in the onset of incubation correlated with mean temperatures just prior
      to laying; however, incubation duration could not be explained by any of our
      temperature variables. Daily incubation intensity varied in response to daily
      maximum temperatures throughout incubation, suggesting female great tits respond
      to temperature cues even in late stages of incubation. Our results suggest that
      multiple aspects of the breeding cycle influence the final timing of peak
      energetic demand. Such adjustments could compensate, in part, for poor initial
      timing, which has significant fitness impacts.

PMID- 29187976
TI  - Genome comparisons indicate recent transfer of wRi-like Wolbachia between sister
      species Drosophila suzukii and D. subpulchrella.
AB  - Wolbachia endosymbionts may be acquired by horizontal transfer, by introgression
      through hybridization between closely related species, or by cladogenic retention
      during speciation. All three modes of acquisition have been demonstrated, but
      their relative frequency is largely unknown. Drosophila suzukii and its sister
      species D. subpulchrella harbor Wolbachia, denoted wSuz and wSpc, very closely
      related to wRi, identified in California populations of D. simulans. However,
      these variants differ in their induced phenotypes: wRi causes significant
      cytoplasmic incompatibility (CI) in D. simulans, but CI has not been detected in
      D. suzukii or D. subpulchrella. Our draft genomes of wSuz and wSpc contain full
      length copies of 703 of the 734 single-copy genes found in wRi. Over these coding
      sequences, wSuz and wSpc differ by only 0.004% (i.e., 28 of 704,883 bp); they are
      sisters relative to wRi, from which each differs by 0.014%-0.015%. Using
      published data from D. melanogaster, Nasonia wasps and Nomada bees to calibrate
      relative rates of Wolbachia versus host nuclear divergence, we conclude that wSuz
      and wSpc are too similar-by at least a factor of 100-to be plausible candidates
      for cladogenic transmission. These three wRi-like Wolbachia, which differ in CI
      phenotype in their native hosts, have different numbers of orthologs of genes
      postulated to contribute to CI; and the CI loci differ at several nucleotides
      that may account for the CI difference. We discuss the general problem of
      distinguishing alternative modes of Wolbachia acquisition, focusing on the
      difficulties posed by limited knowledge of variation in absolute and relative
      rates of molecular evolution for host nuclear genomes, mitochondria, and
      Wolbachia.

PMID- 29187980
TI  - Biological soil crusts determine the germination and growth of two exotic plants.
AB  - In arid and semiarid ecosystems, the potential threats of exotic invasive species
      are enhanced due to increasing human activities. Biological soil crusts (BSCs),
      acting as arid ecosystem engineers, may play an important role in preventing the
      establishment of exotic invasive plants. Our goal was to examine whether BSCs
      could inhibit the establishment of probable exotic plant species originating from
      adjacent grasslands located along the southeast edge of the Tengger Desert. In
      our study, we investigated the effects of three BSC types (cyanobacteria, lichen,
      and moss crusts) under two disturbance conditions (intact and disturbed) on the
      establishment of two exotic plant species (Ceratoides latens and Setaria viridis)
      using indoor experiments. We found both negative and positive effects of BSCs on
      the establishment of the two exotic plant species. Compared with the disturbed
      BSCs, the germination percentages of C. latens and S. viridis were reduced by 54%
      to 87% and 89% to 93%, respectively, in intact BSCs. In contrast, BSCs
      significantly promoted the height growth and aboveground biomass of the two
      exotic plant species (p < .05) by enhancing the soil water and nutrient
      availability for the exotic plants. Our results confirm that BSCs strongly
      suppress the rapid expansion of exotic plant populations by inhibiting
      germination of seed with big size or appendages and have a weak inhibitory effect
      on exotic plant with small and smooth seeds. This may decrease the threat of
      propagation of exotic species. In the meantime, BSCs promote the growth of a few
      successful engraftment seedlings, which increased the beta diversity. Our work
      suggests that better understanding the two opposing effects of BSCs on the
      establishment of exotic plant species in different growth stages (germination and
      growth) is important for maintaining the health and stability of revegetated
      regions.

PMID- 29187979
TI  - Population genomics of the eastern cottonwood (Populus deltoides).
AB  - Despite its economic importance as a bioenergy crop and key role in riparian
      ecosystems, little is known about genetic diversity and adaptation of the eastern
      cottonwood (Populus deltoides). Here, we report the first population genomics
      study for this species, conducted on a sample of 425 unrelated individuals
      collected in 13 states of the southeastern United States. The trees were
      genotyped by targeted resequencing of 18,153 genes and 23,835 intergenic regions,
      followed by the identification of single nucleotide polymorphisms (SNPs). This
      natural P. deltoides population showed low levels of subpopulation
      differentiation (FST = 0.022-0.106), high genetic diversity (thetaW = 0.00100, pi
      = 0.00170), a large effective population size (Ne ~ 32,900), and low to moderate
      levels of linkage disequilibrium. Additionally, genomewide scans for selection
      (Tajima's D), subpopulation differentiation (XTX), and environmental association
      analyses with eleven climate variables carried out with two different methods
      (LFMM and BAYENV2) identified genes putatively involved in local adaptation.
      Interestingly, many of these genes were also identified as adaptation candidates
      in another poplar species, Populus trichocarpa, indicating possible convergent
      evolution. This study constitutes the first assessment of genetic diversity and
      local adaptation in P. deltoides throughout the southern part of its range,
      information we expect to be of use to guide management and breeding strategies
      for this species in future, especially in the face of climate change.

PMID- 29187982
TI  - Transgene flow in Mexican maize revisited: Socio-biological analysis across two
      contrasting farmer communities and seed management systems.
AB  - The flow of transgenes into landraces and wild relatives is an important
      biosafety concern. The case of transgene flow into local maize varieties in
      Mexico (the center of origin of maize) has been intensively debated over the past
      15 years, including legal, political, and environmental disputes fanned by the
      existence of a significant scientific controversy over the methods used for the
      detection of transgenes. The use of diverse approaches and a lack of harmonized
      methods specific to the detection and monitoring of transgenes in landraces have
      generated both positive and negative results regarding contamination of Mexican
      maize with genetically modified material over the years. In this paper, we
      revisit the case of transgene contamination in Mexican maize and present a novel
      research approach based on socio-biological analysis of contrasting communities
      and seed management systems. Two communities were used to investigate how
      different social and biological factors can affect transgene flow and impact
      transgene spread in Mexico. Our results show the presence of transgenes in one
      community and thus support the position that transgenes are highly likely to be
      present in Mexican maize landraces. However, our work also demonstrates that the
      extent and frequency with which transgenes can be found will significantly depend
      on the societal characteristics and seed management systems of the local
      communities. Therefore, we argue that future analysis of transgene presence
      should include social research on the seed management practices in the sampling
      area so that more robust and comprehensive understandings and conclusions can be
      drawn.

PMID- 29187981
TI  - Clonality disguises the vulnerability of a threatened arid zone Acacia.
AB  - Long-lived, widespread plant species are expected to be genetically diverse,
      reflecting the interaction between large population sizes, overlapping
      generations, and gene flow. Such species are thought to be resilient to
      disturbance, but may carry an extinction debt due to reproductive failure.
      Genetic studies of Australian arid zone plant species suggest an unusually high
      frequency of asexuality, polyploidy, or both. A preliminary AFLP genetic study
      implied that the naturally fragmented arid zone tree, Acacia carneorum, is almost
      entirely dependent on asexual reproduction through suckering, and stands may have
      lacked genetic diversity and interconnection even prior to the onset of European
      pastoralism. Here we surveyed microsatellite genetic variation in 20 stands to
      test for variation in life histories and further assessed the conservation status
      of the species by comparing genetic diversity within protected stands in National
      Parks and disturbed range lands. Using herbarium records, we estimate that 219
      stands are extant, all of which occur in the arid zone, west of the Darling River
      in southeastern Australia. With two exceptions, all surveyed stands comprised
      only one multilocus genet and at least eight were putatively polyploid. Although
      some stands comprise thousands of stems, our findings imply that the species as a
      whole may represent ~240 distinct genetic individuals, many of which are
      polyploid, and most are separated by >10 km of unsuitable habitat. With only 34%
      of stands (and therefore genets) occurring within conservation reserves, A.
      carneorum may be at much greater risk of extinction than inferred from on-ground
      census data. Land managers should prioritize on-ground preservation of the
      genotypes within existing reserves, protecting both vegetative suckers and
      seedlings from herbivory. Importantly, three stands are known to set viable seed
      and should be used to generate genetically diverse germ-plasm for ex situ
      conservation, population augmentation, or translocation.

PMID- 29187983
TI  - Tree species distribution in temperate forests is more influenced by soil than by
      climate.
AB  - Knowledge of the ecological requirements determining tree species distributions
      is a precondition for sustainable forest management. At present, the abiotic
      requirements and the relative importance of the different abiotic factors are
      still unclear for many temperate tree species. We therefore investigated the
      relative importance of climatic and edaphic factors for the abundance of 12
      temperate tree species along environmental gradients. Our investigations are
      based on data from 1,075 forest stands across Switzerland including the cold
      induced tree line of all studied species and the drought-induced range boundaries
      of several species. Four climatic and four edaphic predictors represented the
      important growth factors temperature, water supply, nutrient availability, and
      soil aeration. The climatic predictors were derived from the meteorological
      network of MeteoSwiss, and the edaphic predictors were available from soil
      profiles. Species cover abundances were recorded in field surveys. The
      explanatory power of the predictors was assessed by variation partitioning
      analyses with generalized linear models. For six of the 12 species, edaphic
      predictors were more important than climatic predictors in shaping species
      distribution. Over all species, abundances depended mainly on nutrient
      availability, followed by temperature, water supply, and soil aeration. The often
      co-occurring species responded similar to these growth factors. Drought turned
      out to be a determinant of the lower range boundary for some species. We conclude
      that over all 12 studied tree species, soil properties were more important than
      climate variables in shaping tree species distribution. The inclusion of
      appropriate soil variables in species distribution models allowed to better
      explain species' ecological niches. Moreover, our study revealed that the
      ecological requirements of tree species assessed in local field studies and in
      experiments are valid at larger scales across Switzerland.

PMID- 29187984
TI  - Geographic variation in hybridization across a reinforcement contact zone of
      chorus frogs (Pseudacris).
AB  - Reinforcement contact zones, which are secondary contact zones where species are
      diverging in reproductive behaviors due to selection against hybridization,
      represent natural laboratories for studying speciation-in-action. Here, we
      examined replicate localities across the entire reinforcement contact zone
      between North American chorus frogs Pseudacris feriarum and P. nigrita to
      investigate geographic variation in hybridization frequencies and to assess
      whether reinforcement may have contributed to increased genetic divergence within
      species. Previous work indicated these species have undergone reproductive
      character displacement (RCD) in male acoustic signals and female preferences due
      to reinforcement. We also examined acoustic signal variation across the contact
      zone to assess whether signal characteristics reliably predict hybrid index and
      to elucidate whether the degree of RCD predicts hybridization rate. Using
      microsatellites, mitochondrial sequences, and acoustic signal information from
      >1,000 individuals across >50 localities and ten sympatric focal regions, we
      demonstrate: (1) hybridization occurs and (2) varies substantially across the
      geographic range of the contact zone, (3) hybridization is asymmetric and in the
      direction predicted from observed patterns of asymmetric RCD, (4) in one species,
      genetic distance is higher between conspecific localities where one or both have
      been reinforced than between nonreinforced localities, after controlling for
      geographic distance, (5) acoustic signal characters strongly predict hybrid
      index, and (6) the degree of RCD does not strongly predict admixture levels. By
      showing that hybridization occurs in all sympatric localities, this study
      provides the fifth and final line of evidence that reproductive character
      displacement is due to reinforcement in the chorus frog contact zone.
      Furthermore, this work suggests that the dual action of cascade reinforcement and
      partial geographic isolation is promoting genetic diversification within one of
      the reinforced species.

PMID- 29187985
TI  - Insight into the population structure of hardhead silverside, Atherinomorus
      stipes (Teleostei: Atherinidae), in Belize and the Florida Keys using nd2.
AB  - Little is known about the natural history, biology, and population genetic
      structure of the Hardhead Silverside, Atherinomorus stipes, a small schooling
      fish found around islands throughout the Caribbean. Our field observations of A.
      stipes in the cays of Belize and the Florida Keys found that populations tend to
      be in close association with the shoreline in mangrove habitats. Due to this
      potential island-based population structuring, A. stipes represents an ideal
      system to examine questions about gene flow and isolation by distance at
      different geographic scales. For this study, the mitochondrial gene nd2 was
      amplified from 394 individuals collected from seven different Belizean Cays (N =
      175) and eight different Floridian Keys (N = 219). Results show surprisingly high
      haplotype diversity both within and between island-groups, as well as a high
      prevalence of unique haplotypes within each island population. The results are
      consistent with models that require gene flow among populations as well as in
      situ evolution of rare haplotypes. There was no evidence for an isolation by
      distance model. The nd2 gene tree consists of two well-supported monophyletic
      groups: a Belizean-type clade and a Floridian-type clade, indicating potential
      species-level differentiation.

PMID- 29187986
TI  - Spatially varying density dependence drives a shifting mosaic of survival in a
      recovering apex predator (Canis lupus).
AB  - Understanding landscape patterns in mortality risk is crucial for promoting
      recovery of threatened and endangered species. Humans affect mortality risk in
      large carnivores such as wolves (Canis lupus), but spatiotemporally varying
      density dependence can significantly influence the landscape of survival. This
      potentially occurs when density varies spatially and risk is unevenly
      distributed. We quantified spatiotemporal sources of variation in survival rates
      of gray wolves (C. lupus) during a 21-year period of population recovery in the
      Upper Peninsula of Michigan, USA. We focused on mapping risk across time using
      Cox Proportional Hazards (CPH) models with time-dependent covariates, thus
      exploring a shifting mosaic of survival. Extended CPH models and time-dependent
      covariates revealed influences of seasonality, density dependence and experience,
      as well as individual-level factors and landscape predictors of risk. We used
      results to predict the shifting landscape of risk at the beginning, middle, and
      end of the wolf recovery time series. Survival rates varied spatially and
      declined over time. Long-term change was density-dependent, with landscape
      predictors such as agricultural land cover and edge densities contributing
      negatively to survival. Survival also varied seasonally and depended on
      individual experience, sex, and resident versus transient status. The shifting
      landscape of survival suggested that increasing density contributed to greater
      potential for human conflict and wolf mortality risk. Long-term spatial variation
      in key population vital rates is largely unquantified in many threatened,
      endangered, and recovering species. Variation in risk may indicate potential for
      source-sink population dynamics, especially where individuals preemptively occupy
      suitable territories, which forces new individuals into riskier habitat types as
      density increases. We encourage managers to explore relationships between adult
      survival and localized changes in population density. Density-dependent risk maps
      can identify increasing conflict areas or potential habitat sinks which may
      persist due to high recruitment in adjacent habitats.

PMID- 29187987
TI  - Using multiple data types and integrated population models to improve our
      knowledge of apex predator population dynamics.
AB  - Current management of large carnivores is informed using a variety of parameters,
      methods, and metrics; however, these data are typically considered independently.
      Sharing information among data types based on the underlying ecological, and
      recognizing observation biases, can improve estimation of individual and global
      parameters. We present a general integrated population model (IPM), specifically
      designed for brown bears (Ursus arctos), using three common data types for bear
      (U. spp.) populations: repeated counts, capture-mark-recapture, and litter size.
      We considered factors affecting ecological and observation processes for these
      data. We assessed the practicality of this approach on a simulated population and
      compared estimates from our model to values used for simulation and results from
      count data only. We then present a practical application of this general approach
      adapted to the constraints of a case study using historical data available for
      brown bears on Kodiak Island, Alaska, USA. The IPM provided more accurate and
      precise estimates than models accounting for repeated count data only, with
      credible intervals including the true population 94% and 5% of the time,
      respectively. For the Kodiak population, we estimated annual average litter size
      (within one year after birth) to vary between 0.45 [95% credible interval: 0.43;
      0.55] and 1.59 [1.55; 1.82]. We detected a positive relationship between salmon
      availability and adult survival, with survival probabilities greater for females
      than males. Survival probabilities increased from cubs to yearlings to dependent
      young >=2 years old and decreased with litter size. Linking multiple information
      sources based on ecological and observation mechanisms can provide more accurate
      and precise estimates, to better inform management. IPMs can also reduce data
      collection efforts by sharing information among agencies and management units.
      Our approach responds to an increasing need in bear populations' management and
      can be readily adapted to other large carnivores.

PMID- 29187988
TI  - Landscape genomic approach to detect selection signatures in locally adapted
      Brazilian swine genetic groups.
AB  - Samples of 191 animals from 18 different Brazilian locally adapted swine genetic
      groups were genotyped using Illumina Porcine SNP60 BeadChip in order to identify
      selection signatures related to the monthly variation of Brazilian environmental
      variables. Using BayeScan software, 71 SNP markers were identified as FST
      outliers and 60 genotypes (58 markers) were found by Sambetaada software in 371
      logistic models correlated with 112 environmental variables. Five markers were
      identified in both methods, with a Kappa value of 0.073 (95% CI: 0.011-0.134).
      The frequency of these markers indicated a clear north-south country division
      that reflects Brazilian environmental differences in temperature, solar
      radiation, and precipitation. Global spatial territory correlation for
      environmental variables corroborates this finding (average Moran's I = 0.89,
      range from 0.55 to 0.97). The distribution of alleles over the territory was not
      strongly correlated with the breed/genetic groups. These results are congruent
      with previous mtDNA studies and should be used to direct germplasm collection for
      the National gene bank.

PMID- 29187989
TI  - Resource selection by an ectothermic predator in a dynamic thermal landscape.
AB  - Predicting the effects of global climate change on species interactions has
      remained difficult because there is a spatiotemporal mismatch between regional
      climate models and microclimates experienced by organisms. We evaluated resource
      selection in a predominant ectothermic predator using a modeling approach that
      permitted us to assess the importance of habitat structure and local real-time
      air temperatures within the same modeling framework. We radio-tracked 53 western
      ratsnakes (Pantherophis obsoletus) from 2010 to 2013 in central Missouri, USA, at
      study sites where this species has previously been linked to prey population
      demographics. We used Bayesian discrete choice models within an information
      theoretic framework to evaluate the seasonal effects of fine-scale vegetation
      structure and thermal conditions on ratsnake resource selection. Ratsnake
      resource selection was influenced most by canopy cover, canopy cover
      heterogeneity, understory cover, and air temperature heterogeneity. Ratsnakes
      generally preferred habitats with greater canopy heterogeneity early in the
      active season, and greater temperature heterogeneity later in the season. This
      seasonal shift potentially reflects differences in resource requirements and
      thermoregulation behavior. Predicted patterns of space use indicate that
      ratsnakes preferentially selected open habitats in spring and early summer and
      forest-field edges throughout the active season. Our results show that downscaled
      temperature models can be used to enhance our understanding of animal resource
      selection at scales that can be addressed by managers. We suggest that
      conservation of snakes or their prey in a changing climate will require
      consideration of fine-scale interactions between local air temperatures and
      habitat structure.

PMID- 29187990
TI  - Increasing habitat complexity on seawalls: Investigating large- and small-scale
      effects on fish assemblages.
AB  - The construction of artificial structures in the marine environment is increasing
      globally. Eco-engineering aims to mitigate the negative ecological impacts of
      built infrastructure through designing structures to be multifunctional,
      benefiting both humans and nature. To date, the focus of eco-engineering has
      largely been on benefits for benthic invertebrates and algae. Here, the potential
      effect of eco-engineered habitats designed for benthic species on fish was
      investigated. Eco-engineered habitats ("flowerpots") were added to an intertidal
      seawall in Sydney Harbour, Australia. Responses of fish assemblages to the added
      habitats were quantified at two spatial scales; large (among seawalls) and small
      (within a seawall). Data were collected during high tide using cameras attached
      to the seawall to observe pelagic and benthic fish. At the larger spatial scale,
      herbivores, planktivores, and invertebrate predators were generally more abundant
      at the seawall with the added flowerpots, although results were temporally
      variable. At the smaller spatial scale, certain benthic species were more
      abundant around flowerpots than at the adjacent control areas of seawall,
      although there was no general pattern of differences in species density and
      trophic group abundance of pelagic fish between areas of the seawall with or
      without added habitats. Although we did not find consistent, statistically
      significant findings throughout our study, the field of research to improve fish
      habitat within human-use constraints is promising and important, although it is
      in its early stages (it is experimental and requires a lot of trial and error).
      To advance this field, it is important to document when effects were detected,
      and when they were not, so that others can refine the designs or scale of habitat
      enhancements or their study approaches (e.g., sampling protocols).

PMID- 29187991
TI  - Introduction history overrides social factors in explaining genetic structure of
      females in Mediterranean mouflon.
AB  - Fine-scale spatial genetic structure of populations results from social and
      spatial behaviors of individuals such as sex-biased dispersal and philopatry.
      However, the demographic history of a given population can override such socio
      spatial factors in shaping genetic variability when bottlenecks or founder events
      occurred in the population. Here, we investigated whether socio-spatial
      organization determines the fine-scale genetic structure for both sexes in a
      Mediterranean mouflon (Ovis gmelini musimon * Ovis sp.) population in southern
      France 60 years after its introduction. Based on multilocus genotypes at 16 loci
      of microsatellite DNA (n = 230 individuals), we identified three genetic groups
      for females and two for males, and concurrently defined the same number of socio
      spatial units using both GPS-collared individuals (n = 121) and visual
      resightings of marked individuals (n = 378). The socio-spatial and genetic
      structures did not match, indicating that the former was not the main driver of
      the latter for both sexes. Beyond this structural mismatch, we found significant,
      yet low, genetic differentiation among female socio-spatial groups, and no
      genetic differentiation in males, with this suggesting female philopatry and male
      biased gene flow, respectively. Despite spatial disconnection, females from the
      north of the study area were genetically closer to females from the south, as
      indicated by the spatial analysis of the genetic variability, and this pattern
      was in accordance with the common genetic origin of their founders. To conclude,
      more than 14 generations later, genetic signatures of first introduction are not
      only still detectable among females, but they also represent the main factor
      shaping their present-time genetic structure.

PMID- 29187992
TI  - Field evidence challenges the often-presumed relationship between early male
      maturation and female-biased sexual size dimorphism.
AB  - Female-biased sexual size dimorphism (SSD) is often considered an epiphenomenon
      of selection for the increased mating opportunities provided by early male
      maturation (i.e., protandry). Empirical evidence of the adaptive significance of
      protandry remains nonetheless fairly scarce. We use field data collected
      throughout the reproductive season of an SSD crab spider, Mecaphesa celer, to
      test two hypotheses: Protandry provides fitness benefits to males, leading to
      female-biased SSD, or protandry is an indirect consequence of selection for small
      male size/large female size. Using field-collected data, we modeled the
      probability of mating success for females and males according to their timing of
      maturation. We found that males matured earlier than females and the proportion
      of virgin females decreased abruptly early in the season, but unexpectedly
      increased afterward. Timing of female maturation was not related to clutch size,
      but large females tended to have more offspring than small females. Timing of
      female and male maturation was inversely related to size at adulthood, as early
      maturing individuals were larger than late-maturing ones, suggesting that both
      sexes exhibit some plasticity in their developmental trajectories. Such
      plasticity indicates that protandry could co-occur with any degree and direction
      of SSD. Our calculation of the probability of mating success along the season
      shows multiple male maturation time points with similar predicted mating success.
      This suggests that males follow multiple strategies with equal success, trading
      off access to virgin females with intensity of male-male competition. Our results
      challenge classic hypotheses linking protandry and female-biased SSD, and
      emphasize the importance of directly testing the often-assumed relationships
      between co-occurring animal traits.

PMID- 29187994
TI  - Detection of barriers to dispersal is masked by long lifespans and large
      population sizes.
AB  - Population genetic analyses of species inhabiting fragmented landscapes are
      essential tools for conservation. Occasionally, analyses of fragmented
      populations find no evidence of isolation, even though a barrier to dispersal is
      apparent. In some cases, not enough time may have passed to observe divergence
      due to genetic drift, a problem particularly relevant for long-lived species with
      overlapping generations. Failing to consider this quality during population
      structure analyses could result in incorrect conclusions about the impact of
      fragmentation on the species. We designed a model to explore how lifespan and
      population size influence perceived population structure of isolated populations
      over time. This iterative model tracked how simulated populations of variable
      lifespan and population size were affected by drift alone, using a freshwater
      mussel, Quadrula quadrula (mapleleaf), as a model system. In addition to
      exhibiting dramatic lifespan variability among species, mussels are also highly
      imperiled and exhibit fragmentation by dams throughout the range of many species.
      Results indicated that, unless population size was small (<50 individuals) or
      lifespan short (<22 years), observing genetic divergence among populations was
      unlikely. Even if wild populations are isolated, observing population structure
      in long-lived mussels from modern damming practices is unlikely because it takes
      longer for population structure to develop in these species than most North
      American dams have existed. Larger population sizes and longer lifespans increase
      the time needed for significant divergence to occur. This study helps illuminate
      the factors that influence genetic responses by populations to isolation and
      provides a useful model for conservation-oriented research.

PMID- 29187993
TI  - Phylogeography of Schizopygopsis stoliczkai (Cyprinidae) in Northwest Tibetan
      Plateau area.
AB  - Schizopygopsis stoliczkai (Cyprinidae, subfamily Schizothoracinae) is one of the
      major freshwater fishes endemic to the northwestern margin of the Tibetan
      Plateau. In the current study, we used mitochondrial DNA markers cytochrome b
      (Cyt b) and 16S rRNA (16S), as well as the nuclear marker, the second intron of
      the nuclear beta-actin gene (Act2), to uncover the phylogeography of S.
      stoliczkai. In total, we obtained 74 haplotypes from 403 mitochondrial
      concatenated sequences. The mtDNA markers depict the phylogenetic structures of
      S. stoliczkai, which consist of clade North and clade South. The split time of
      the two clades is dated back to 4.27 Mya (95% HPD = 1.96-8.20 Mya). The estimated
      split time is earlier than the beginning of the ice age of Pleistocene (2.60
      Mya), suggesting that the northwestern area of the Tibetan Plateau probably
      contain at least two glacial refugia for S. stoliczkai. SAMOVA supports the
      formation of four groups: (i) the Karakash River group; (ii) The Lake Pangong
      group; (iii) the Shiquan River group; (iv) the Southern Basin group. Clade North
      included Karakash River, Lake Pangong, and Shiquan River groups, while seven
      populations of clade South share the haplotypes. Genetic diversity, star-like
      network, BSP analysis, as well as negative neutrality tests indicate recent
      expansions events of S. stoliczkai. Conclusively, our results illustrate the
      phylogeography of S. stoliczkai, implying the Shiquan River is presumably the
      main refuge for S. stoliczkai.

PMID- 29187995
TI  - Neutral lipid fatty acid composition as trait and constraint in Collembola
      evolution.
AB  - Functional traits determine the occurrence of species along environmental
      gradients and their coexistence with other species. Understanding how traits
      evolved among coexisting species helps to infer community assembly processes. We
      propose fatty acid composition in consumer tissue as a functional trait related
      to both food resources and physiological functions of species. We measured
      phylogenetic signal in fatty acid profiles of 13 field-sampled Collembola
      (springtail) species and then combined the data with published fatty acid
      profiles of another 24 species. Collembola fatty acid profiles generally showed
      phylogenetic signal, with related species resembling each other. Long-chain
      polyunsaturated fatty acids, related to physiological functions, demonstrated
      phylogenetic signal. In contrast, most food resource biomarker fatty acids and
      the ratios between bacterial, fungal, and plant biomarker fatty acids exhibited
      no phylogenetic signal. Presumably, fatty acids related to physiological
      functions have been constrained during Collembola evolutionary history: Species
      with close phylogenetic affinity experienced similar environments during
      divergence, while niche partitioning in food resources among closely related
      species favored species coexistence. Measuring phylogenetic signal in
      ecologically relevant traits of coexisting species provides an evolutionary
      perspective to contemporary assembly processes of ecological communities.
      Integrating phylogenetic comparative methods with community phylogenetic and
      trait-based approaches may compensate for the limitations of each method when
      used alone and improve understanding of processes driving and maintaining
      assembly patterns.

PMID- 29187996
TI  - Incorporating phylogenetic information for the definition of floristic districts
      in hyperdiverse Amazon forests: Implications for conservation.
AB  - Using complementary metrics to evaluate phylogenetic diversity can facilitate the
      delimitation of floristic units and conservation priority areas. In this study,
      we describe the spatial patterns of phylogenetic alpha and beta diversity,
      phylogenetic endemism, and evolutionary distinctiveness of the hyperdiverse
      Ecuador Amazon forests and define priority areas for conservation. We established
      a network of 62 one-hectare plots in terra firme forests of Ecuadorian Amazon. In
      these plots, we tagged, collected, and identified every single adult tree with
      dbh >=10 cm. These data were combined with a regional community phylogenetic tree
      to calculate different phylogenetic diversity (PD) metrics in order to create
      spatial models. We used Loess regression to estimate the spatial variation of
      taxonomic and phylogenetic beta diversity as well as phylogenetic endemism and
      evolutionary distinctiveness. We found evidence for the definition of three
      floristic districts in the Ecuadorian Amazon, supported by both taxonomic and
      phylogenetic diversity data. Areas with high levels of phylogenetic endemism and
      evolutionary distinctiveness in Ecuadorian Amazon forests are unprotected.
      Furthermore, these areas are severely threatened by proposed plans of oil and
      mining extraction at large scales and should be prioritized in conservation
      planning for this region.

PMID- 29187997
TI  - Internode morphometrics and allometry of Tonkin Cane Pseudosasa amabilis.
AB  - Pseudosasa amabilis (McClure) (Poales: Gramineae) is a typical bamboo species
      naturally distributed in large area of south China and famous for its culm
      strength. Although bamboos were found to share the same development rule, the
      detailed internode morphology of bamboo culm was actually not fully expressed. We
      explored internode morphology of P. amabilis using 11 different physical
      parameters in different dimensions (1-4). As Taylor's power law (TPL) is
      generally applicable to describe relationship between mean and variance of
      population density, here we used TPL to evaluate the differences between
      internodes, and further, the relationship between dimension and TPL. Results
      showed that length (L), hollow radius (HR), hollow area (HA), hollow cylinder
      volume (HCV), total cylinder volume (TCV), density (De), and weight (W) all
      presented positive skewed distribution in varying degrees. For the basic one
      dimensional parameters, the 9th internode was the longest, the 7th the heaviest,
      while thickness (T) decreased with internodes. Diameter (D) decreased in general
      but with an inconspicuous local mode at the 5-6th internodes, potentially due to
      the rapid height growth. The longest (9th) internode was the "turning point" for
      T-D and HR-D relationships. Scatter plot changing trends of W to the one
      dimensional parameters after the heaviest (7th) internode were reversed,
      indicating a deceleration of growth speed. TPL was not holding well in one
      dimensional parameters (R2: 0.5413-0.8125), but keep increasing as the
      parameter's dimension increasing (R2 > 0.92 for two-dimensional, R2 > 0.97 for
      three-dimensional, and R2 > 0.99 for four-dimensional parameters.), suggesting an
      emergence mechanism of TPL related to both the physical dimensions of
      morphological measures and the allometric growth of bamboo. From the physical
      fundamental level, all existences are the expression of energy distribution in
      different dimensions, implying a more general rule that energy distribution holds
      better TPL in higher dimension level.

PMID- 29187998
TI  - Quantifying resilience of multiple ecosystem services and biodiversity in a
      temperate forest landscape.
AB  - Resilience is increasingly being considered as a new paradigm of forest
      management among scientists, practitioners, and policymakers. However, metrics of
      resilience to environmental change are lacking. Faced with novel disturbances,
      forests may be able to sustain existing ecosystem services and biodiversity by
      exhibiting resilience, or alternatively these attributes may undergo either a
      linear or nonlinear decline. Here we provide a novel quantitative approach for
      assessing forest resilience that focuses on three components of resilience,
      namely resistance, recovery, and net change, using a spatially explicit model of
      forest dynamics. Under the pulse set scenarios, we explored the resilience of
      nine ecosystem services and four biodiversity measures following a one-off
      disturbance applied to an increasing percentage of forest area. Under the pulse +
      press set scenarios, the six disturbance intensities explored during the pulse
      set were followed by a continuous disturbance. We detected thresholds in net
      change under pulse + press scenarios for the majority of the ecosystem services
      and biodiversity measures, which started to decline sharply when disturbance
      affected >40% of the landscape. Thresholds in net change were not observed under
      the pulse scenarios, with the exception of timber volume and ground flora species
      richness. Thresholds were most pronounced for aboveground biomass, timber volume
      with respect to the ecosystem services, and ectomycorrhizal fungi and ground
      flora species richness with respect to the biodiversity measures. Synthesis and
      applications. The approach presented here illustrates how the multidimensionality
      of stability research in ecology can be addressed and how forest resilience can
      be estimated in practice. Managers should adopt specific management actions to
      support each of the three components of resilience separately, as these may
      respond differently to disturbance. In addition, management interventions aiming
      to deliver resilience should incorporate an assessment of both pulse and press
      disturbances to ensure detection of threshold responses to disturbance, so that
      appropriate management interventions can be identified.

PMID- 29187999
TI  - Effects of seasonality and environmental gradients on Spartina alterniflora
      allometry and primary production.
AB  - : Predictions of how salt marsh primary production and carbon storage will
      respond to environmental change can be improved through detailed datasets
      documenting responses to real-world environmental variation. To address a
      shortage of detailed studies of natural variation, we examined drivers of
      Spartina alterniflora stem allometry and productivity in seven marshes across
      three regions in southern Louisiana. Live-stem allometry varied spatially and
      seasonally, generally with short stems weighing more (and tall stems weighing
      less) in the summer and fall, differences that persist even after correcting for
      flowering. Strong predictive relationships exist between allometry parameters
      representing emergent stem mass and mass accumulation rates, suggesting that S.
      alterniflora populations navigate a trade-off between larger mass at emergence
      and faster rates of biomass accumulation. Aboveground production and belowground
      production were calculated using five and four approaches, respectively. End-of
      season aboveground biomass was a poor proxy for increment-based production
      measures. Aboveground production (Smalley) ranged from 390 to 3,350 g m-2 year-1
      across all marshes and years. Belowground production (max-min) was on average
      three times higher than aboveground; total production ranged from 1,400 to 8,500
      g m-2 year-1. Above- and belowground production were both positively correlated
      with dissolved nutrient concentrations and negatively correlated to salinity.
      SYNTHESIS: Interannual variation in water quality is sufficient to drive above-
      and belowground productivity. The positive relationship between nutrients and
      belowground production indicates that inputs of nutrients and freshwater may
      increase salt marsh carbon storage and ecosystem resilience to sea level rise.

PMID- 29188000
TI  - Optimizing methods to estimate zooplankton concentration based on generalized
      patterns of patchiness inside ballast tanks and ballast water discharges.
AB  - Zooplankton populations are spatially heterogeneous in nature and inside ship
      ballast tanks. Sampling methods should take heterogeneity into account,
      particularly when estimating quantitative variables such as abundance or
      concentration. It is particularly important to generate unbiased estimates of
      zooplankton concentration in ballast water when assessing compliance with new
      international ballast water discharge standards. We measured spatial
      heterogeneity of zooplankton within ballast water using three sampling
      methodologies. In-tank pump samples were collected at fixed depths within the
      vertical part of the ballast tank (side tank). Vertical net-haul samples were
      collected from the upper portion of the tank as a depth-integrated and
      historically relevant method. In-line, time-integrated samples were collected
      during ballast discharge by an isokinetic sample probe, likely representing the
      double bottom part of the ballast tank. The bias and precision associated with
      each sampling method were evaluated in reference to the estimated average
      abundance of the entire ballast tank, which was modeled from the data collected
      by all methods. In-tank pump samples provided robust evidence for vertical
      stratification of zooplankton concentration in the side tank. A consistent trend
      was also observed for in-line discharge samples, with zooplankton concentration
      decreasing through time as the ballast tank is being discharged. Sample
      representativeness, as compared to the tank average, varied depending on the
      depth or tank volume discharged. In-line discharge samples provided the least
      biased and most precise estimate of average tank abundance (having lowest mean
      squared error) when collected during the time frame of 20%-60% of the tank volume
      being discharged. Results were consistent across five trips despite differences
      in ballast water source, season, and age.

PMID- 29188001
TI  - Responses to a warming world: Integrating life history, immune investment, and
      pathogen resistance in a model insect species.
AB  - Environmental temperature has important effects on the physiology and life
      history of ectothermic animals, including investment in the immune system and the
      infectious capacity of pathogens. Numerous studies have examined individual
      components of these complex systems, but little is known about how they integrate
      when animals are exposed to different temperatures. Here, we use the Indian meal
      moth (Plodia interpunctella) to understand how immune investment and disease
      resistance react and potentially trade-off with other life-history traits. We
      recorded life-history (development time, survival, fecundity, and body size) and
      immunity (hemocyte counts, phenoloxidase activity) measures and tested resistance
      to bacterial (E. coli) and viral (Plodia interpunctella granulosis virus)
      infection at five temperatures (20-30 degrees C). While development time,
      lifespan, and size decreased with temperature as expected, moths exhibited
      different reproductive strategies in response to small changes in temperature. At
      cooler temperatures, oviposition rates were low but tended to increase toward the
      end of life, whereas warmer temperatures promoted initially high oviposition
      rates that rapidly declined after the first few days of adult life. Although
      warmer temperatures were associated with strong investment in early reproduction,
      there was no evidence of an associated trade-off with immune investment.
      Phenoloxidase activity increased most at cooler temperatures before plateauing,
      while hemocyte counts increased linearly with temperature. Resistance to
      bacterial challenge displayed a complex pattern, whereas survival after a viral
      challenge increased with rearing temperature. These results demonstrate that
      different immune system components and different pathogens can respond in
      distinct ways to changes in temperature. Overall, these data highlight the scope
      for significant changes in immunity, disease resistance, and host-parasite
      population dynamics to arise from small, biologically relevant changes to
      environmental temperature. In light of global warming, understanding these
      complex interactions is vital for predicting the potential impact of insect
      disease vectors and crop pests on public health and food security.

PMID- 29188002
TI  - Eggshells as hosts of bacterial communities: An experimental test of the
      antimicrobial egg coloration hypothesis.
AB  - Oviparous animals have evolved multiple defenses to prevent microbes from
      penetrating their eggs and causing embryo mortality. In birds, egg constituents
      such as lysozyme and antibodies defend against microbial infestation, but
      eggshell pigments might also impact survival of bacteria. If so, microbes could
      exert an important selective pressure on the evolution of eggshell coloration. In
      a previous lab experiment, eggshell protoporphyrin caused drastic mortality in
      cultures of Gram positive, but not Gram negative, bacteria when exposed to light.
      Here, we test this "photodynamic antimicrobial hypothesis" in a field experiment.
      In a paired experimental design, we placed sanitized brown, protoporphyrin-rich
      chicken eggs alongside white eggs that lack protoporphyrin. We deployed eggs for
      48 hr without incubation, as can occur between laying and incubation, when
      microbial infection risk is highest. Eggs were placed on the open ground exposed
      to sunlight and in dark underground storm-petrel burrows. We predicted that the
      proportion of Gram-positive bacteria on brown eggs should be lower when exposed
      to sunlight than when kept in the dark, but we expected no such difference for
      white eggs. Although our data revealed variation in bacterial community
      composition, the proportion of Gram-positive bacteria on eggshells did not vary
      by egg color, and there was no interaction between egg color and location.
      Instead, Gram-positive bacteria were proportionally more common on eggs on the
      ground than eggs in burrows. Overall, our experiment did not support the
      photodynamic antimicrobial hypothesis. The diverse range of avian egg colors is
      generated by just two pigments, but over 10 hypotheses have been proposed for the
      evolution of eggshell color. If our results are generalizable, eggshell
      protoporphyrin might not play a substantial role in defending eggs against
      microbes, which narrows the field of candidate hypotheses for the evolution of
      avian eggshell coloration.

PMID- 29188003
TI  - Intraspecific and interspecific competition induces density-dependent habitat
      niche shifts in an endangered steppe bird.
AB  - Interspecific competition is a dominant force in animal communities that induces
      niche shifts in ecological and evolutionary time. If competition occurs, niche
      expansion can be expected when the competitor disappears because resources
      previously inaccessible due to competitive constraints can then be exploited
      (i.e., ecological release). Here, we aimed to determine the potential effects of
      interspecific competition between the little bustard (Tetrax tetrax) and the
      great bustard (Otis tarda) using a multidimensional niche approach with habitat
      distribution data. We explored whether the degree of niche overlap between the
      species was a density-dependent function of interspecific competition. We then
      looked for evidences of ecological release by comparing measures of niche breadth
      and position of the little bustard between allopatric and sympatric situations.
      Furthermore, we evaluated whether niche shifts could depend not only on the
      presence of great bustard but also on the density of little and great bustards.
      The habitat niches of these bustard species partially overlapped when co
      occurring, but we found no relationship between degree of overlap and great
      bustard density. In the presence of the competitor, little bustard's niche was
      displaced toward increased use of the species' primary habitat. Little bustard's
      niche breadth decreased proportionally with great bustard density in sympatric
      sites, in consistence with theory. Overall, our results suggest that density
      dependent variation in little bustard's niche is the outcome of interspecific
      competition with the great bustard. The use of computational tools like kernel
      density estimators to obtain multidimensional niches should bring novel insights
      on how species' ecological niches behave under the effects of interspecific
      competition in ecological communities.

PMID- 29188004
TI  - Leaf-IT: An Android application for measuring leaf area.
AB  - The use of plant functional traits has become increasingly popular in ecological
      studies because plant functional traits help to understand key ecological
      processes in plant species and communities. This also includes changes in
      diversity, inter- and intraspecific interactions, and relationships of species at
      different spatiotemporal scales. Leaf traits are among the most important traits
      as they describe key dimensions of a plant's life history strategy. Further, leaf
      area is a key parameter with relevance for other traits such as specific leaf
      area, which in turn correlates with leaf chemical composition, photosynthetic
      rate, leaf longevity, and carbon investment. Measuring leaf area usually involves
      the use of scanners and commercial software and can be difficult under field
      conditions. We present Leaf-IT, a new smartphone application for measuring leaf
      area and other trait-related areas. Leaf-IT is free, designed for scientific
      purposes, and runs on Android 4 or higher. We tested the precision and accuracy
      using objects with standardized area and compared the area measurements of real
      leaves with the well-established, commercial software WinFOLIA using the Altman
      Bland method. Area measurements of standardized objects show that Leaf-IT
      measures area with high accuracy and precision. Area measurements with Leaf-IT of
      real leaves are comparable to those of WinFOLIA. Leaf-IT is an easy-to-use
      application running on a wide range of smartphones. That increases the
      portability and use of Leaf-IT and makes it possible to measure leaf area under
      field conditions typical for remote locations. Its high accuracy and precision
      are similar to WinFOLIA. Currently, its main limitation is margin detection of
      damaged leaves or complex leaf morphologies.

PMID- 29188005
TI  - Connectivity, persistence, and loss of high abundance areas of a recovering
      marine fish population in the Northwest Atlantic Ocean.
AB  - In the early 1990s, the Northwest Atlantic Ocean underwent a fisheries-driven
      ecosystem shift. Today, the iconic cod (Gadus morhua) remains at low levels,
      while Atlantic halibut (Hippoglossus hippoglossus) has been increasing since the
      mid-2000s, concomitant with increasing interest from the fishing industry.
      Currently, our knowledge about halibut ecology is limited, and the lack of
      recovery in other collapsed groundfish populations has highlighted the danger of
      overfishing local concentrations. Here, we apply a Bayesian hierarchical
      spatiotemporal approach to model the spatial structure of juvenile Atlantic
      halibut over 36 years and three fisheries management regimes using three model
      parameters to characterize the resulting spatiotemporal abundance structure:
      persistence (similarity of spatial structure over time), connectivity (coherence
      of temporal pattern over space), and spatial variance (variation across the
      seascape). Two areas of high juvenile abundance persisted through three decades
      whereas two in the northeast are now diminished, despite the increased abundance
      and landings throughout the management units. The persistent areas overlap with
      full and seasonal area closures, which may act as refuges from fishing.
      Connectivity was estimated to be 250 km, an order of magnitude less than the
      distance assumed by the definition of the Canadian management units (~2,000 km).
      The underlying question of whether there are distinct populations within the
      southern stock unit cannot be answered with this model, but the smaller ~250 km
      scale of coherent temporal patterns suggests more complex population structure
      than previously thought, which should be taken into consideration by fishery
      management.

PMID- 29188006
TI  - Radiation of the polymorphic Little Devil poison frog (Oophaga sylvatica) in
      Ecuador.
AB  - Some South American poison frogs (Dendrobatidae) are chemically defended and use
      bright aposematic colors to warn potential predators of their unpalatability.
      Aposematic signals are often frequency-dependent where individuals deviating from
      a local model are at a higher risk of predation. However, extreme diversity in
      the aposematic signal has been documented in poison frogs, especially in Oophaga.
      Here, we explore the phylogeographic pattern among color-divergent populations of
      the Little Devil poison frog Oophaga sylvatica by analyzing population structure
      and genetic differentiation to evaluate which processes could account for color
      diversity within and among populations. With a combination of PCR amplicons
      (three mitochondrial and three nuclear markers) and genome-wide markers from a
      double-digested RAD (ddRAD) approach, we characterized the phylogenetic and
      genetic structure of 199 individuals from 13 populations (12 monomorphic and 1
      polymorphic) across the O. sylvatica distribution. Individuals segregated into
      two main lineages by their northern or southern latitudinal distribution. A high
      level of genetic and phenotypic polymorphism within the northern lineage suggests
      ongoing gene flow. In contrast, low levels of genetic differentiation were
      detected among the southern lineage populations and support recent range
      expansions from populations in the northern lineage. We propose that a
      combination of climatic gradients and structured landscapes might be promoting
      gene flow and phylogenetic diversification. Alternatively, we cannot rule out
      that the observed phenotypic and genomic variations are the result of genetic
      drift on near or neutral alleles in a small number of genes.

PMID- 29188007
TI  - Enhancing the diversity of breeding invertebrates within field margins of
      intensively managed grassland: Effects of alternative management practices.
AB  - Severe declines in biodiversity have been well documented for many taxonomic
      groups due to intensification of agricultural practices. Establishment and
      appropriate management of arable field margins can improve the diversity and
      abundance of invertebrate groups; however, there is much less research on field
      margins within grassland systems. Three grassland field margin treatments
      (fencing off the existing vegetation "fenced"; fencing with rotavation and
      natural regeneration "rotavated" and; fencing with rotavation and seeding
      "seeded") were compared to a grazed control in the adjacent intensively managed
      pasture. Invertebrates were sampled using emergence traps to investigate species
      breeding and overwintering within the margins. Using a manipulation experiment,
      we tested whether the removal of grazing pressure and nutrient inputs would
      increase the abundance and richness of breeding invertebrates within grassland
      field margins. We also tested whether field margin establishment treatments, with
      their different vegetation communities, would change the abundance and richness
      of breeding invertebrates in the field margins. Exclusion of grazing and nutrient
      inputs led to increased abundance and richness in nearly all invertebrate groups
      that we sampled. However, there were more complex effects of field margin
      establishment treatment on the abundance and richness of invertebrate taxa. Each
      of the three establishment treatments supported a distinct invertebrate
      community. The removal of grazing from grassland field margins provided a greater
      range of overwintering/breeding habitat for invertebrates. We demonstrate the
      capacity of field margin establishment to increase the abundance and richness in
      nearly all invertebrate groups in study plots that were located on previously
      more depauperate areas of intensively managed grassland. These results from
      grassland field margins provide evidence to support practical actions that can
      inform Greening (Pillar 1) and agri-environment measures (Pillar 2) of the Common
      Agricultural Policy (CAP). Before implementing specific management regimes, the
      conservation aims of agri-environment measures should be clarified by defining
      the target species or taxonomic groups.

PMID- 29188008
TI  - Ecotypic differences in the phenology of the tundra species Eriophorum vaginatum
      reflect sites of origin.
AB  - Eriophorum vaginatum is a tussock-forming sedge that contributes significantly to
      the structure and primary productivity of moist acidic tussock tundra. Locally
      adapted populations (ecotypes) have been identified across the geographical
      distribution of E. vaginatum; however, little is known about how their growth and
      phenology differ over the course of a growing season. The growing season is short
      in the Arctic and therefore exerts a strong selection pressure on tundra species.
      This raises the hypothesis that the phenology of arctic species may be poorly
      adapted if the timing and length of the growing season change. Mature E.
      vaginatum tussocks from across a latitudinal gradient (65-70 degrees N) were
      transplanted into a common garden at a central location (Toolik Lake, 68 degrees
      38'N, 149 degrees 36'W) where half were warmed using open-top chambers. Over two
      growing seasons (2015 and 2016), leaf length was measured weekly to track growth
      rates, timing of senescence, and biomass accumulation. Growth rates were similar
      across ecotypes and between years and were not affected by warming. However,
      southern populations accumulated significantly more biomass, largely because they
      started to senesce later. In 2016, peak biomass and senescence of most
      populations occurred later than in 2015, probably induced by colder weather at
      the beginning of the growing season in 2016, which caused a delayed start to
      growth. The finish was delayed as well. Differences in phenology between
      populations were largely retained between years, suggesting that the amount of
      time that these ecotypes grow has been selected by the length of the growing
      seasons at their respective home sites. As potential growing seasons lengthen, E.
      vaginatum may be unable to respond appropriately as a result of genetic control
      and may have reduced fitness in the rapidly warming Arctic tundra.

PMID- 29188009
TI  - Conservation implications for dingoes from the maternal and paternal genome:
      Multiple populations, dog introgression, and demography.
AB  - It is increasingly common for apex predators to face a multitude of complex
      conservation issues. In Australia, dingoes are the mainland apex predator and
      play an important role in ecological functioning. Currently, however, they are
      threatened by hybridization with modern domestic dogs in the wild. As a
      consequence, we explore how increasing our understanding of the evolutionary
      history of dingoes can inform management and conservation decisions. Previous
      research on whole mitochondrial genome and nuclear data from five geographical
      populations showed evidence of two distinct lineages of dingo. Here, we present
      data from a broader survey of dingoes around Australia using both mitochondrial
      and Y chromosome markers and investigate the timing of demographic expansions.
      Biogeographic data corroborate the presence of at least two geographically
      subdivided genetic populations, southeastern and northwestern. Demographic
      modeling suggests that dingoes have undergone population expansion in the last
      5,000 years. It is not clear whether this stems from expansion into vacant niches
      after the extinction of thylacines on the mainland or indicates the arrival date
      of dingoes. Male dispersal is much more common than female, evidenced by more
      diffuse Y haplogroup distributions. There is also evidence of likely historical
      male biased introgression from domestic dogs into dingoes, predominately within
      southeastern Australia. These findings have critical practical implications for
      the management and conservation of dingoes in Australia; particularly a focus
      must be placed upon the threatened southeastern dingo population.

PMID- 29188010
TI  - Effects of macronutrient intake on the lifespan and fecundity of the marula fruit
      fly, Ceratitis cosyra (Tephritidae): Extreme lifespan in a host specialist.
AB  - In insects, lifespan and reproduction are strongly associated with nutrition. The
      ratio and amount of nutrients individuals consume affect their life expectancy
      and reproductive investment. The geometric framework (GF) enables us to explore
      how animals regulate their intake of multiple nutrients simultaneously and
      determine how these nutrients interact to affect life-history traits of interest.
      Studies using the GF on host-generalist tephritid flies have highlighted trade
      offs between longevity and reproductive effort in females, mediated by the
      protein-to-carbohydrate (P:C) ratio that individuals consume. Here, we tested how
      P and C intake affect lifespan (LS) in both sexes, and female lifetime (LEP), and
      daily (DEP) egg production, in Ceratitis cosyra, a host-specialist tephritid fly.
      We then determined the P:C ratio that C. cosyra defends when offered a choice of
      foods. Female LS was optimized at a 0:1 P:C ratio, whereas to maximize their
      fecundity, females needed to consume a higher P:C ratio (LEP = 1:6 P:C; DEP =
      1:2.5 P:C). In males, LS was also optimized at a low P:C ratio of 1:10. However,
      when given the opportunity to regulate their intake, both sexes actively defended
      a 1:3 P:C ratio, which is closer to the target for DEP than either LS or LEP. Our
      results show that female C. cosyra experienced a moderate trade-off between LS
      and fecundity. Moreover, the diets that maximized expression of LEP and DEP were
      of lower P:C ratio than those required for optimal expression of these traits in
      host-generalist tephritids or other generalist insects.

PMID- 29188011
TI  - Evidence of separate subgroups of juvenile southern bluefin tuna.
AB  - Archival tagging studies of southern bluefin tuna (SBT , Thunnus maccoyii) have
      revealed that juveniles residing in the Great Australian Bight (GAB) over the
      austral summer undertake seasonal cyclic migrations to the southeast Indian Ocean
      and the Tasman Sea during winter. However, there remains disagreement about the
      extent of mixing between juvenile SBT regularly caught by longline fleets south
      of Africa and those observed in the GAB. Some researchers have argued that
      archival tag recoveries indicate most juveniles reside in the GAB over the
      austral summer. Others have suggested that recoveries of conventional and
      archival tags are better explained by a juvenile population consisting of
      separate groups on the eastern and western sides of the Indian Ocean with limited
      intermixing. We present analyses of catch and tag recovery data and re-examine
      archival tagging studies. The evidence provided strongly favors the hypothesis of
      separate juvenile subgroups, or contingents, with limited intermixing. We draw
      some tentative conclusions about the nature of the putative contingents and
      discuss some implications of these findings for the interpretation of existing
      datasets and future research priorities. We also provide the first evidence that
      the migration choices of juveniles that summer in the GAB are influenced by
      fidelity to winter feeding grounds and suggest this helps explain the collapse of
      the surface fishery off New South Wales in the 1980s.

PMID- 29188012
TI  - Creating, generating and comparing random network models with Network Randomizer.
AB  - Biological networks are becoming a fundamental tool for the investigation of high
      throughput data in several fields of biology and biotechnology. With the
      increasing amount of information, network-based models are gaining more and more
      interest and new techniques are required in order to mine the information and to
      validate the results. We have developed an app for the Cytoscape platform which
      allows the creation of randomized networks and the randomization of existing,
      real networks. Since there is a lack of tools for generating and randomizing
      networks, our app helps researchers to exploit different, well known random
      network models which could be used as a benchmark for validating real datasets.
      We also propose a novel methodology for creating random weighted networks
      starting from experimental data. Finally the app provides a statistical tool
      which compares real versus random attributes, in order to validate all the
      numerical findings. In summary, our app aims at creating a standardised
      methodology for the validation of the results in the context of the Cytoscape
      platform.

PMID- 29188013
TI  - Scaling-up primary health care-based prevention and management of alcohol use
      disorder at the municipal level in middle-income countries in Latin America:
      Background and pre-protocol for a three-country quasi-experimental study.
AB  - Background: While primary health care (PHC)-based prevention and management of
      alcohol use disorder (AUD) is clinically effective and cost-effective, it remains
      poorly implemented in routine practice. Systematic reviews and multi-country
      studies have demonstrated the ability of training and support programmes to
      increase PHC-based screening and brief advice activity to reduce heavy drinking.
      However, gains have been only modest and short term at best. WHO studies have
      concluded that a more effective uptake could be achieved by embedding PHC
      activity within broader community and municipal support.  Protocol: A quasi
      experimental study will compare PHC-based prevention and management of AUD,
      operationalized by heavy drinking, in three intervention cities from Colombia,
      Mexico and Peru with three comparator cities from the same countries. In the
      implementation cities, primary health care units (PHCUs) will receive training
      embedded within ongoing supportive municipal action over an 18-month
      implementation period. In the comparator cities, practice as usual will continue
      at both municipal and PHCU levels. The primary outcome will be the proportion of
      consulting adult patients intervened with (screened and advice given to screen
      positives). The study is powered to detect a doubling of the outcome measure from
      an estimated 2.5/1,000 patients at baseline. Formal evaluation points will be at
      baseline, mid-point and end-point of the 18-month implementation period. We will
      present the ratio (plus 95% confidence interval) of the proportion of patients
      receiving intervention in the implementation cities with the proportions in the
      comparator cities. Full process evaluation will be undertaken, coupled with an
      analysis of potential contextual, financial and political-economy influencing
      factors.  Discussion: This multi-country study will test the extent to which
      embedding PHC-based prevention and management of alcohol use disorder with
      supportive municipal action leads to improved scale-up of more patients with
      heavy drinking receiving appropriate advice and treatment.

PMID- 29188014
TI  - Assessment of injection safety in Ha Dong General Hospital, Hanoi, in 2012.
AB  - Background: Injection is one of the most frequently used medical methods to
      introduce drugs or other substances into the body for purposes of treatment or
      prevention. Unsafe injection can cause adverse outcomes, such as abscess and
      anaphylactic shock, and increases the risk of blood-borne transmission of viruses
      to patients and health care workers, as well as the community. Recognizing the
      importance of injection safety, in 2000 the Vietnamese Ministry of Health (MOH)
      collaborated with the Vietnam Nurses Association to launch the "Safe injection"
      program throughout the country, including Hanoi. Methods: This cross-sectional
      study, combining quantitative and qualitative analysis, was conducted from
      February to August 2012 in Ha Dong General Hospital using a structured
      questionnaire and observation checklist. The target population of the study was
      109 nurses working in clinical departments and 436 injections were observed.
      Results: The percentage of nurses who are familiar with injection safety
      standards was found to be 82.6%. The proportion of practical injections that met
      the 23 standards of injection safety set by the MOH amounted to 22.2%. The
      factors related to safe injection practice of nurses who are younger age group
      (OR=3.1; p<0.05) and lower amount of working years (OR=2.8; p<0.05). Conclusions:
      A low proportion of nurses performed correct safety injection practice, which
      raises the need for further training about this issue, especially among older
      nurses.

PMID- 29188016
TI  - An analysis of characteristics of post-authorisation studies registered on the
      ENCePP EU PAS Register.
AB  - BACKGROUND: The objective of this study was to investigate the study design
      characteristics of Post-Authorisation Studies (PAS) requested by the European
      Medicines Agency which were recorded on the European Union (EU) PAS Register held
      by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance
      (ENCePP). METHODS: We undertook a cross-sectional descriptive analysis of all
      studies registered on the EU PAS Register as of 18 th October 2016. RESULTS: We
      identified a total of 314 studies on the EU PAS Register, including 81 (26%)
      finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified,
      205 (65%) included risk assessment in their scope, 133 (42%) included drug
      utilisation and 94 (30%) included effectiveness evaluation. Just over half of the
      studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4
      (1%) used a hybrid design combining both approaches. Risk assessment and
      effectiveness studies were more likely to use primary data capture (60% and 85%
      respectively as compared to 39% and 14% respectively for secondary). The converse
      was true for drug utilisation studies where 59% were secondary vs. 39% for
      primary. For type 2 diabetes mellitus, database studies were more commonly used
      (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs)
      whereas for studies in oncology, primary data capture were more likely to be used
      (85% vs 4% chart review, and 11% database study designs). CONCLUSIONS: Results of
      this analysis show that study objectives and therapeutic area influence PAS
      design in terms of type of data capture used.

PMID- 29188017
TI  - Identification of the ventral occipital visual field maps in the human brain.
AB  - The location and topography of the first three visual field maps in the human
      brain, V1-V3, are well agreed upon and routinely measured across most
      laboratories. The position of 4 th visual field map, 'hV4', is identified with
      less consistency in the neuroimaging literature.  Using magnetic resonance
      imaging data, we describe landmarks to help identify the position and borders of
      'hV4'. The data consist of anatomical images, visualized as cortical meshes to
      highlight the sulcal and gyral patterns, and functional data obtained from
      retinotopic mapping experiments, visualized as eccentricity and angle maps on the
      cortical surface. Several features of the functional and anatomical data can be
      found across nearly all subjects and are helpful for identifying the location and
      extent of the hV4 map. The medial border of hV4 is shared with the posterior,
      ventral portion of V3, and is marked by a retinotopic representation of the upper
      vertical meridian. The anterior border of hV4 is shared with the VO-1 map, and
      falls on a retinotopic representation of the peripheral visual field, usually
      coincident with the posterior transverse collateral sulcus. The ventro-lateral
      edge of the map typically falls on the inferior occipital gyrus, where functional
      MRI artifacts often obscure the retinotopic data. Finally, we demonstrate the
      continuity of retinotopic parameters between hV4 and its neighbors; hV4 and V3v
      contain iso-eccentricity lines in register, whereas hV4 and VO-1 contain iso
      polar angle lines in register. Together, the multiple constraints allow for a
      consistent identification of the hV4 map across most human subjects.

PMID- 29188018
TI  - Atopic dermatitis patients show increases in serum C-reactive protein levels,
      correlating with skin disease activity.
AB  - Background: Atopic dermatitis (AD), the most common chronic inflammatory skin
      disease, is evolving as a systemic disease, and associated systemic inflammation
      is possibly linked to increases in cardiovascular disease. Methods: We assessed
      levels of the inflammatory marker CRP in 59 patients with moderate-to-severe AD
      compared to matched healthy controls, and to determine correlation with skin
      disease severity. Clinical severity was measured using SCORing of Atopic
      Dermatitis (SCORAD) and body surface area (BSA). Control subjects (n=118),
      matched by age, gender, smoking status and ethnicity, were obtained from the
      National Health and Nutrition Survey (NHANES). Results: AD patients had
      significantly increased serum CRP levels compared to controls (0.7+/-1.0 vs.
      0.4+/-0.7mg/dl; p=0.001). CRP levels were significantly correlated with both
      SCORAD (r=0.427, p=0.0008) and BSA (r=0.407, p=0.0015).  IgE levels in AD were
      highly elevated (median 2903U/ml, IQR [234,10655]), but only weakly correlated
      with SCORAD (r=0.282, p=0.0427) and BSA (r=0.382, p=0.0052), but not with CRP
      levels. AD patients also showed increased LDH levels, but without significant
      correlations with disease severity (SCORAD, BSA) or CRP. Conclusions: Our study
      strongly supports CRP as a marker for disease severity in moderate-to-severe AD
      patients, further demonstrating its chronic systemic nature.

PMID- 29188015
TI  - A multi-disciplinary perspective on emergent and future innovations in peer
      review.
AB  - Peer review of research articles is a core part of our scholarly communication
      system. In spite of its importance, the status and purpose of peer review is
      often contested. What is its role in our modern digital research and
      communications infrastructure? Does it perform to the high standards with which
      it is generally regarded? Studies of peer review have shown that it is prone to
      bias and abuse in numerous dimensions, frequently unreliable, and can fail to
      detect even fraudulent research. With the advent of Web technologies, we are now
      witnessing a phase of innovation and experimentation in our approaches to peer
      review. These developments prompted us to examine emerging models of peer review
      from a range of disciplines and venues, and to ask how they might address some of
      the issues with our current systems of peer review. We examine the functionality
      of a range of social Web platforms, and compare these with the traits underlying
      a viable peer review system: quality control, quantified performance metrics as
      engagement incentives, and certification and reputation. Ideally, any new systems
      will demonstrate that they out-perform current models while avoiding as many of
      the biases of existing systems as possible. We conclude that there is
      considerable scope for new peer review initiatives to be developed, each with
      their own potential issues and advantages. We also propose a novel hybrid
      platform model that, at least partially, resolves many of the technical and
      social issues associated with peer review, and can potentially disrupt the entire
      scholarly communication system. Success for any such development relies on
      reaching a critical threshold of research community engagement with both the
      process and the platform, and therefore cannot be achieved without a significant
      change of incentives in research environments.

PMID- 29188019
TI  - lakemorpho: Calculating lake morphometry metrics in R.
AB  - Metrics describing the shape and size of lakes, known as lake morphometry
      metrics, are important for any limnological study. In cases where a lake has long
      been the subject of study these data are often already collected and are openly
      available. Many other lakes have these data collected, but access is challenging
      as it is often stored on individual computers (or worse, in filing cabinets) and
      is available only to the primary investigators. The vast majority of lakes fall
      into a third category in which the data are not available. This makes broad scale
      modelling of lake ecology a challenge as some of the key information about in
      lake processes are unavailable. While this valuable in situ information may be
      difficult to obtain, several national datasets exist that may be used to model
      and estimate lake morphometry. In particular, digital elevation models and
      hydrography have been shown to be predictive of several lake morphometry metrics.
      The R package lakemorpho has been developed to utilize these data and estimate
      the following morphometry metrics: surface area, shoreline length, major axis
      length, minor axis length, major and minor axis length ratio, shoreline
      development, maximum depth, mean depth, volume, maximum lake length, mean lake
      width, maximum lake width, and fetch. In this software tool article we describe
      the motivation behind developing lakemorpho, discuss the implementation in R, and
      describe the use of lakemorpho with an example of a typical use case.

PMID- 29188020
TI  - Case Report: Spontaneous cholecystocutaneous fistula, a rare cholethiasis
      complication.
AB  - One of the most unusual complications in cholethiasis is spontaneous
      cholecystocutaneous fistula, which has only been reported a few times in the
      literature.  We report the case of a 76 year old man who presented with a right
      hypochondrium subcutaneous abscess, with pain evoked through palpation.  No
      comorbidity in the patient's medical history were noted.   Confirmation of
      cholecystocutaneous fistula was made using the proper diagnostic process, which
      is computed tomography with contrast media, followed by hepatobiliary MRI. This
      confirmed the presence of a fistulous pathway between the gallbladder and the
      skin.  The patient underwent cholecystectomy surgery and open laparotomy with en
      block aponeurotic muscle, skin and fistula orifice excision.

PMID- 29188022
TI  - Induced spawning of siban fish Cyclocheilichthys apogon using Ovaprim.
AB  - Background: The objective of the present study was to examine the effect of
      Ovaprim dosage on the latency period, relative number of ovulated eggs,
      fertilization, hatching, and survival rates of the siban fish, Cyclocheilichthys
      apogon. Methods: Three dosages of Ovaprim were tested in this study, namely 0.3
      ml kg-1 of broodfish body weight, 0.5 ml kg-1 body weight, and 0.7 ml kg-1 body
      weight, plus control (without Ovaprim).  Results: The results showed that the
      best latency period, relative number of ovulated eggs, fertilization, hatching,
      and survival rates were obtained at a dosage of 0.7 ml kg -1 body weight.
      Conclusions: The best dosage of Ovaprim for siban fish from the dosages tested,
      was determined to be 0.7 ml kg-1 body weight.

PMID- 29188023
TI  - Draft genomes of two Australian strains of the plant pathogen, Phytophthora
      cinnamomi.
AB  - Background: The oomycete plant pathogen, Phytophthora cinnamomi, is responsible
      for the destruction of thousands of species of native Australian plants, as well
      as several crops, such as avocado and macadamia, and has one of the widest host
      plant ranges of the Phytophthora genus. The currently available genome of P.
      cinnamomi is based on an atypical strain and has large gaps in its assembly. To
      further studies of the pathogenicity of this species, especially in Australia,
      more robust assemblies of the genomes of more typical strains are required. Here
      we report the genome sequencing, draft assembly, and preliminary annotation of
      two geographically separated Australian strains of P. cinnamomi. Findings:  Some
      308 million raw reads were generated for the two strains. Independent genome
      assembly produced final genomes of 62.8 Mb (in 14,268 scaffolds) and 68.1 Mb (in
      10,084 scaffolds), which are comparable in size and contiguity to other
      Phytophthora genomes. Gene prediction yielded > 22,000 predicted protein-encoding
      genes within each genome, while BUSCO assessment showed 82.5% and 81.8% of the
      eukaryote universal single-copy orthologs to be present in the assembled genomes,
      respectively. Conclusions: The assembled genomes of two geographically distant
      isolates of Phytophthora cinnamomi will provide a valuable resource for further
      comparative analysis and evolutionary studies of this destructive pathogen, and
      further annotation of the presented genomes may yield possible targets for novel
      pathogen control methods.

PMID- 29188024
TI  - Managing Persistent Hypoxemia: what is new?
AB  - Mechanical ventilation is the standard life-support technique for patients with
      severe acute respiratory failure. However, some patients develop persistent and
      refractory hypoxemia because their lungs are so severely damaged that they are
      unable to respond to the application of high inspired oxygen concentration and
      high levels of positive end-expiratory pressure. In this article, we review
      current knowledge on managing persistent hypoxemia in patients with injured
      lungs.

PMID- 29188021
TI  - Illustrative examples of probable transfer of resistance determinants from food
      animals to humans: Streptothricins, glycopeptides, and colistin.
AB  - Use, overuse, and misuse of antimicrobials contributes to selection and
      dissemination of bacterial resistance determinants that may be transferred to
      humans and constitute a global public health concern. Because of the continued
      emergence and expansion of antimicrobial resistance, combined with the lack of
      novel antimicrobial agents, efforts are underway to preserve the efficacy of
      current available life-saving antimicrobials in humans. As a result, uses of
      medically important antimicrobials in food animal production have generated
      debate and led to calls to reduce both antimicrobial use and the need for use.
      This manuscript, commissioned by the World Health Organization (WHO) to help
      inform the development of the WHO guidelines on the use of medically important
      antimicrobials in food animals, includes three illustrations of antimicrobial use
      in food animal production that has contributed to the selection-and subsequent
      transfer-of resistance determinants from food animals to humans. Herein,
      antimicrobial use and the epidemiology of bacterial resistance are described for
      streptothricins, glycopeptides, and colistin. Taken together, these historical
      and current narratives reinforce the need for actions that will preserve the
      efficacy of antimicrobials.

PMID- 29188025
TI  - Recent advances in understanding bile acid homeostasis.
AB  - Bile acids are derived from cholesterol to facilitate intestinal nutrient
      absorption and biliary secretion of cholesterol. Recent studies have identified
      bile acids as signaling molecules that activate nuclear farnesoid X receptor
      (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as
      TGR5) to maintain metabolic homeostasis and protect liver and other tissues and
      cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex
      mechanism of feedback and feedforward regulation that is not completely
      understood. This review will cover recent advances in bile acid signaling and
      emerging concepts about the classic and alternative bile acid synthesis pathway,
      bile acid composition and bile acid pool size, and intestinal bile acid signaling
      and gut microbiome in regulation of bile acid homeostasis.

PMID- 29188026
TI  - Is temperature an important variable in recovery after mild traumatic brain
      injury?
AB  - With nearly 42 million mild traumatic brain injuries (mTBIs) occurring worldwide
      every year, understanding the factors that may adversely influence recovery after
      mTBI is important for developing guidelines in mTBI management. Extensive
      clinical evidence exists documenting the detrimental effects of elevated
      temperature levels on recovery after moderate to severe TBI. However, whether
      elevated temperature alters recovery after mTBI or concussion is an active area
      of investigation. Individuals engaged in exercise and competitive sports
      regularly experience body and brain temperature increases to hyperthermic levels
      and these temperature increases are prolonged in hot and humid ambient
      environments. Thus, there is a strong potential for hyperthermia to alter
      recovery after mTBI in a subset of individuals at risk for mTBI. Preclinical mTBI
      studies have found that elevating brain temperature to 39 degrees C before mTBI
      significantly increases neuronal death within the cortex and hippocampus and also
      worsens cognitive deficits. This review summarizes the pathology and behavioral
      problems of mTBI that are exacerbated by hyperthermia and discusses whether
      hyperthermia is a variable that should be considered after concussion and mTBI.
      Finally, underlying pathophysiological mechanisms responsible for hyperthermia
      induced altered responses to mTBI and potential gender considerations are
      discussed.

PMID- 29188027
TI  - Recent advances in the understanding and management of bipolar disorder in
      adults.
AB  - This article focuses on some aspects of recent progress in the neurobiology and
      treatment of bipolar disorder (BD) in adults. A molecular-genetic approach to the
      etiopathogenesis of the illness resulted in the findings of a genetic overlap
      between BD and other major psychiatric disorders. Furthermore, a poly-gene
      environmental interaction in the development of the illness has been
      demonstrated. For the management of BD, new drugs with putative mood-stabilizing
      properties have been introduced in the past two decades. However, none of these
      can surpass lithium, the prototype mood-stabilizer, still considered the most
      specific drug for BD. Recent research on lithium, besides providing new data on
      the neurobiology of BD, has confirmed anti-suicidal, immunomodulatory, and
      neuroprotective properties of this drug.

PMID- 29188028
TI  - Evolution of blood pressure management in acute intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) remains a prevalent and severe cause of death and
      disability worldwide. Control of the hypertensive response in acute ICH has been
      a mainstay of ICH management, yet the optimal approaches and the yield of
      recommended strategies have been difficult to establish despite a large body of
      literature. Over the years, theoretical and observed risks and benefits of
      intensive blood pressure reduction in ICH have been studied in the form of animal
      models, radiographic studies, and two recent large, randomized patient trials. In
      this article, we review the historical and developing data and discuss remaining
      questions surrounding blood pressure management in acute ICH.

PMID- 29188030
TI  - Monosodium glutamate as a tool to reduce sodium in foodstuffs: Technological and
      safety aspects.
AB  - Sodium chloride (NaCl) is the most commonly used ingredient to provide salty
      taste to foods. However, excess sodium in the bloodstream has been associated
      with the development of several chronic noncommunicable diseases. In order to
      limit sodium intake to levels considered safe, the World Health Organization
      (WHO) recommends for adults a daily intake of not more than 5 g of NaCl (less
      than 2 g of sodium). One of the strategic actions recommended by the Pan American
      Health Organization (PAHO) to reduce sodium intake is reformulation of processed
      foods. This recommendation indicates there is an urgent need to find salt
      substitutes, and umami compounds have been pointed as an alternative strategy.
      Like salty, umami is also a basic taste and the major compound associated to
      umami is monosodium L-glutamate (MSG). The available scientific data on the
      toxicity of MSG has been evaluated by scientific committees and regulatory
      agencies. The Joint FAO/WHO Expert Committee on Food Additives and the Scientific
      Committee on Food of the European Commission established an acceptable daily
      intake (ADI) not specified, which indicated that the substance offers no health
      risk when used as a food additive. The United States Food and Drug Administration
      and the Federation of American Societies for Experimental Biology classified MSG
      as a Generally Recognized as Safe (GRAS) substance. In this paper, an overview
      about salty and umami taste physiology, the potential applications of MSG use to
      reduce sodium content in specific industrialized foods and safety aspects of MSG
      as food additive are presented.

PMID- 29188029
TI  - Distributional benefits of tobacco tax and smoke-free workplaces in China: A
      modeling study.
AB  - Background: Tobacco taxation and smoke-free workplaces reduce smoking, tobacco
      related premature deaths and associated out-of-pocket health care expenditures.
      We examine the distributional consequences of a price increase in tobacco
      products through an excise tax hike, and of an implementation of smoke-free
      workplaces, in China. Methods: We use extended cost-effectiveness analysis (ECEA)
      to evaluate, across income quintiles of the male population (the large majority
      of Chinese smokers), the premature deaths averted, the change in tax revenues
      generated, and the financial risk protection procured (eg, poverty cases averted,
      defined as the number of individuals no longer facing tobacco-related out-of
      pocket expenditures for disease treatment, that would otherwise impoverish them),
      that would follow a 75% increase in cigarette prices through substantial
      increments in excise tax fully passed onto consumers, and a nationwide total
      implementation of workplace smoking bans. Results: A 75% increase in cigarette
      prices would avert about 24 million premature deaths among the current Chinese
      male population, with a third among the bottom income quintile, increase
      additional tax revenues by US$ 46 billion annually, and prevent around 9 million
      poverty cases, 19% of which among the bottom income quintile. Implementation of
      smoking bans in workplaces would avert about 12 million premature deaths, with a
      fifth among the bottom income quintile, decrease tax revenues by US$ 7 billion
      annually, and prevent around 4 million poverty cases, 12% of which among the
      bottom income quintile. Conclusions: Increased excise taxes on tobacco products
      and workplace smoking bans can procure large health and economic benefits to the
      Chinese population, especially among the poor.

PMID- 29188031
TI  - Effects of different ozonized slurry-ice treatments and superchilling storage (-1
      degrees C) on microbial spoilage of two important pelagic fish species.
AB  - Combining different preservative treatments for improving quality and safety of
      fishery products increasingly receives global research attention. Consistent with
      this pursuit, the current research was undertaken to determine the effects of
      different ozonized slurry-ice treatments and superchilling (-1 degrees C) storage
      on microbial spoilage of European anchovy (Eugraulis encrasicolus) and sardine
      (Sardina pilchardus), which are two commercially important pelagic fish species.
      After the catch (within <5 hr) and at defined scheduled storage times, ozone has
      been discharged once on sardine (herein referred to as "One-T") and
      repeatedly/sequentially on European anchovy (herein referred to as "Seq-T").
      Microbiological analyses enumerated total viable count (TVC), Bacillus spp.,
      Enterobacteriaceae, Lactobacillus spp., Moraxella spp., Shewanella spp., Listeria
      monocytogenes and Pseudomonas spp. Independent of potential antimicrobial effects
      of ozone during superchilling storage, no Listeria spp., Shewanella spp.,
      Moraxella spp., and Bacillus spp. were found in all processed samples. While
      Enterobacteriaceae and Lactobacillus spp. were detected at below 1 log cfu/g,
      both TVC and Pseudomonas spp. proliferated at different rates throughout
      superchilling storage. The repeated ozone-treated ("Seq-T") showed lower TVC and
      Pseudomonas spp. values compared with one-time treated ("One-T") slurry-iced and
      control samples. Thus, combined slurry-ice and superchilling storage at Seq-T
      produced improved antimicrobial activity over One-T application. Largely,
      ozonized slurry-ice outcomes/results appear promising thanks to superchilling
      storage.

PMID- 29188032
TI  - Effects of quince seed, almond, and tragacanth gum coating on the banana slices
      properties during the process of hot air drying.
AB  - Due to early deterioration of banana in drying process, almond, quince seed, and
      tragacanth gums as edible coatings were determined. For this purpose, banana
      slices were coated in 0.7% solution of each gum and one group remained uncoated
      as the control. The samples were examined at specific times considering the
      weight loss, color analyzing (a*, b*, and L*) through the method computer vision,
      color difference index, browning index, and rehydration after the samples being
      dried. The results showed that the weight loss of the coated samples was
      significantly (p < .05) higher than the uncoated samples which can be due to the
      alteration or destruction of the cell membrane. The almond gum-coated samples had
      significantly a lower ultimate browning index and quince seed gum-coated samples
      showed the highest rehydration. So, the gums coating is an effective way to
      preserve the quality characteristics of the banana slices.

PMID- 29188033
TI  - Simple methods to reduce major allergens Ara h 1 and Ana o 1/2 in peanut and
      cashew extracts.
AB  - Whole peanut or cashew extracts are usually used in immunotherapy. Reducing major
      allergen(s) in the extracts may lessen their side effects. Three methods were
      evaluated to reduce major allergens in peanut extracts: (1) p-aminobenzamidine;
      (2) magnetic agarose beads; and (3) extraction of a commercial peanut flour at pH
      7, respectively. The first two methods were also used to reduce major allergens
      in cashew extracts. After treatments, samples were evaluated by SDS-PAGE. pABA
      treated samples were also analyzed for IgE binding in western blot. We found that
      the methods resulted in peanut extracts lacking detectable Ara h 1 but containing
      Ara h 2/6 and cashew extract lacking Ana o 1/2, but containing Ana o 3.
      Consequently, reduced IgE binding was observed. We conclude that the methods are
      useful for producing peanut or cashew extract with little Ara h 1 or Ana o 1/2.

PMID- 29188034
TI  - Viscoelastic properties of sweet potato complementary porridges as influenced by
      endogenous amylases.
AB  - Sweet potato (Ipomoea batatas L.) roots contain amylolytic enzymes, which
      hydrolyze starch thus having the potential to affect the viscosity of sweet
      potato porridges provided the appropriate working conditions for the enzymes are
      attained. In this study, the effect of sweet potato variety, postharvest handling
      conditions, freshly harvested and room/ambient stored roots (3 weeks), and slurry
      solids content on the viscoelastic properties of complementary porridges prepared
      using amylase enzyme activation technique were investigated. Five temperatures
      (55 degrees C, 65 degrees C, 70 degrees C, 75 degrees C, and 80 degrees C) were
      used to activate sweet potato amylases and the optimum temperature was found to
      be 75 degrees C. Stored sweet potato roots had higher soluble solids (0Brix)
      content in the pastes compared to fresh roots. In all samples, activation of
      amylases at 75 degrees C caused changes in the viscoelastic parameters: phase
      angle (tan delta) and complex viscosity (eta*). Postharvest handling conditions
      and slurry solids content significantly affected the viscoelastic properties of
      the porridges with flours from stored roots yielding viscous (liquid-like)
      porridges and fresh roots producing elastic (solid-like) porridges. Increase in
      slurry solids content caused reduction in the phase angle values and increase in
      the viscosity of the sweet potato porridges. The viscosity of the porridges
      decreased with storage of sweet potato roots. These results provide a possibility
      for exploiting sweet potato endogenous amylases in the preparation of
      complementary porridges with both drinkable viscosities and appropriate energy
      and nutrient densities for children with varying energy needs.

PMID- 29188035
TI  - Oxidative changes in lipids, proteins, and antioxidants in yogurt during the
      shelf life.
AB  - Oxidation processes in milk and yogurt during the shelf life can result in an
      alteration of protein and lipid constituents. Therefore, the antioxidant
      properties of yogurt in standard conditions of preservation were evaluated. Total
      phenols, free radical scavenger activity, degree of lipid peroxidation, and
      protein oxidation were determined in plain and skim yogurts with or without fruit
      puree. After production, plain, skim, plain berries, and skim berries yogurts
      were compared during the shelf life up to 9 weeks. All types of yogurts revealed
      a basal antioxidant activity that was higher when a fruit puree was present but
      gradually decreased during the shelf life. However, after 5-8 weeks, antioxidant
      activity increased again. Both in plain and berries yogurts lipid peroxidation
      increased until the seventh week of shelf life and after decreased, whereas
      protein oxidation of all yogurts was similar either in the absence or presence of
      berries and increased during shelf life. During the shelf life, a different
      behavior between lipid and protein oxidation takes place and the presence of
      berries determines a protection only against lipid peroxidation.

PMID- 29188036
TI  - Influence of development, postharvest handling, and storage conditions on the
      carbohydrate components of sweetpotato (Ipomea batatas Lam.) roots.
AB  - Changes in total starch and reducing sugar content in five sweetpotato varieties
      were investigated weekly during root development and following subjection of the
      roots to different postharvest handling and storage conditions. Freshly harvested
      (noncured) roots and cured roots (spread under the sun for 4 days at 29-31
      degrees C and 63-65% relative humidity [RH]) were separately stored at ambient
      conditions (23 degrees C-26 degrees C and 70-80% RH) and in a semiunderground pit
      (19-21 degrees C and 90-95% RH). Changes in pasting properties of flour from
      sweetpotato roots during storage were analyzed at 14-day intervals. Significant
      varietal differences (p < .05) in total starch, sucrose, glucose, maltose, and
      fructose concentrations were registered. The total starch and sucrose content of
      the roots did not change significantly (p < .05) during root development (72.4
      and 7.4%, respectively), whereas the average concentrations of glucose, maltose,
      and fructose decreased markedly (0.46-0.18%, 0.55-0.28%, and 0.43-0.21%),
      respectively. Storage led to decrease in total starch content (73-47.7%) and
      increase in sucrose and glucose concentrations (8.1-11.2% and 0.22-1.57%,
      respectively). Storage also resulted in reduction in sweetpotato flour pasting
      viscosities. Curing resulted in increased sucrose and glucose concentrations (9.1
      11.2% and 0.45-0.85%, respectively) and marked reduction (p < .05) in total
      starch content (72.9-47.6%). This resulted in low pasting viscosities compared to
      flour from storage of uncured roots. These findings show that significant changes
      occur in the carbohydrate components of sweetpotato roots during storage compared
      to development and present an opportunity for diverse utilization of flours from
      sweetpotato roots in the food industry.

PMID- 29188037
TI  - Influence of physicochemical parameters on storage stability: Microbiological
      quality of fresh unpasteurized fruit juices.
AB  - Fresh juices rich in health and nutritional benefits are valued for their fresh
      flavor, taste, and aroma. These juices' quality however is affected by factors
      like temperature, light, and microbiological contamination significantly changing
      physicochemical parameters and storage stability. Physicochemical and
      microbiological analyses of passion fruit, pineapple, and mango juices in dark
      and light bottles at 24 degrees C and 4 degrees C were conducted in Kampala,
      Uganda for 12 days. Physicochemical parameters significantly reduced (p < .05)
      storage stability of fresh juices, while no significant changes (p > .05) were
      observed for the microbiological analyses. pH values ranged from 3.0 to 4.2
      (dark) bottles and 2.9 to 4.0 (light) bottles for juices at 24 degrees C and 4
      degrees C.  degrees Brix values were from 1.0 to 5.5 for dark and clear bottles
      at 24 degrees C and 4 degrees C. TTA (%) values ranged from 1.1 to 7.2 (dark)
      bottles and 1.1 to 7.4 for (light) bottles at 24 degrees C and 4 degrees C.
      Ascorbic acid content ranged from 3.5 to 61.0 mg/ 100 ml and 5.5 to 56.7 mg/100
      ml for juices in dark and clear bottles, respectively. total plate counts ranged
      from 1.3 * 10___ to 3.3 * 107 CFU/ml (dark bottles at 24 degrees C) to 3.5 * 103
      to 3.3 * 108 CFU/ml (dark bottles at 4 degrees C). For juices in light bottles,
      total plate counts ranged from 1.8 * 10___ to 8.0 * 107 CFU/ml (24 degrees C) and
      2.7 * 10___ to 1.5 * 108 CFU/ml (4 degrees C). High microbial loads suggest the
      use of poor processing techniques and lack of good hygiene which lower quality
      and reduce storage stability of juices. Storage temperature greatly reduces
      physicochemical parameters both at ambient and refrigeration temperatures. This
      implies that temperature control for unpasteurized juices is critical in order to
      inhibit microorganism metabolic activities which accelerate biodeterioration
      leading to spoilage and short shelf life. Fresh unpasteurized juices stored at 24
      degrees C and 4 degrees C may safely be consumed within 1 and 2 days,
      respectively.

PMID- 29188038
TI  - Effects of cooking and fermentation on the chemical composition, functional, and
      antinutritional properties of kariya (Hildergardia barteri) seeds.
AB  - The effects of natural fermentation and cooking on kariya seeds functional
      properties, chemical composition, and antinutritional properties were evaluated.
      Result showed a reduction in antinutritional properties and improvement in
      protein content which were observed to increase with cooking (at 100 degrees C)
      and fermentation period (24-96 hr). Functional analyses showed an increase in
      foaming and emulsion properties, while water absorption capacity and swelling
      power were observed to likewise increase with an increasing temperature between
      60 degrees C and 90 degrees C. There was also an improvement in foaming
      properties with increase in salt (NaCl) concentration, while emulsifying property
      decreases with an increase in salt (NaCl) concentration. Based on the result of
      the findings of this study, it can be stated that the cooking and fermentation
      processes employed in this study can enhance the domestic and industrial
      utilization of these seeds.

PMID- 29188039
TI  - Nutritional variation in baobab (Adansonia digitata L.) fruit pulp and seeds
      based on Africa geographical regions.
AB  - Baobab (Adansonia digitata L.) is an indigenous fruit tree associated with the
      Savannah drylands of sub-Saharan Africa. Local communities mainly utilize the
      leaves, pulp, and seeds of baobab as a source of food and for income generation.
      The present study was conducted to determine the nutritive attributes of baobab
      fruit pulp and seeds across provenances in east, west, and southern Africa and to
      determine whether the nutrient content varied with the provenance of origin. Pulp
      and seed proximate composition and mineral element concentration were determined
      using the AOAC 1984 methods and inductively coupled plasma atomic emission
      spectroscopy (ICP-AES), respectively. The results showed that there exist
      significant variation (p < .05) in pulp moisture, protein, fiber, ash, and
      elemental content among provenances. The highest mean pulp crude fiber (8.68 g
      100 g-1 dw) was recorded in Kenya. At country level, Malawi had the highest mean
      pulp potassium (22.2 mg g-1), calcium (4,300 mg kg-1), magnesium (2,300 mg kg-1),
      sodium (1,000 mg kg-1), and phosphorus (1,100 mg kg-1) levels. Kenya had the
      highest mean pulp iron (57.4 MUg g-1) and manganese (27.2 MUg g-1) content, while
      Mali had the lowest iron (13.1 MUg g-1) and manganese (8.6 MUg g-1). At country
      level, the mean seed calcium content was highest (3,200 mg kg-1) in Malawi and
      lowest (2,000 mg kg-1) in Kenya. The highest mean iron content of 63.7 MUg g-1
      was recorded in seeds from Kenya, while the lowest (25.8 MUg g-1) was in Mali.
      Baobab seed mineral and proximate content varied significantly (p < .001) among
      the selected countries. Overall, baobab fruit pulp and seeds contain significant
      amounts of nutritionally essential minerals and proximate components but the
      amounts varied significantly among the selected countries. This variation offers
      opportunities for selecting provenances to concentrate on during germplasm
      collection for conservation and domestication of baobab.

PMID- 29188040
TI  - Evaluation of peanut skin and grape seed extracts to inhibit growth of foodborne
      pathogens.
AB  - Peanut skin extract (PSE) and grape seed extract (GSE) are derived from waste
      products in the wine and peanut industries, respectively. Both have high
      concentrations of polyphenols, known to possess antioxidant and antimicrobial
      properties. PSE primarily contains "A-type" procyanidins, while GSE primarily
      contains "B-type" procyanidins. These differ structurally, but are both isomers
      of epicatechin dimers. The objective of this study was to evaluate the
      antimicrobial effects of PSE containing A-type procyanidins and GSE containing B
      type procyanidins against select foodborne pathogens (Listeria monocytogenes,
      Escherichia coli O157:H7, and Salmonella Typhimurium). The minimum inhibitory
      concentration (MIC) of the two extracts on L. monocytogenes, E. coli O157:H7, and
      S. Typhimurium was determined using the pour plate method. GSE had a
      significantly lower MIC (p <= .05) than PSE for L. monocytogenes (GSE = 60.6 ppm,
      PSE > 68.2 ppm) and S. Typhimurium (GSE = 45.7 ppm, PSE = 60.6 ppm), but no
      difference in inhibition of E. coli O157:H7. Since GSE contributed to greater
      inhibition, GSE extract was fractionated into monomer-rich (consisting primarily
      of catechins, epicatechins, and epicatechin gallates) and oligomer-rich
      (consisting of dimers, trimers, tetramers, up to decamers) components. Growth
      curves of all three pathogens in the presence of full extract, monomer and
      oligomer fractions were compared separately. None of the extracts inhibited S.
      Typhimurium growth. Generally, the extract containing greater oligomer components
      inhibited growth of L. monocytogenes and E. coli O157:H7 when compared to the
      control. Results indicate that an extract with type B procyanidins higher in
      oligomers may have greater antimicrobial properties.

PMID- 29188041
TI  - Effect of processing methods on the nutritional content of three traditional
      vegetables leaves: Amaranth, black nightshade and jute mallow.
AB  - The study assessed changes in nutritional content of some commonly consumed
      traditional vegetables subjected to postharvest processes. Amaranth (Amaranthus
      cruentus L.), black nightshade (Solanum scabrum Mill.) and jute mallow (Corchorus
      olitorius L.) leaves used as vegetables were subjected to blanching, boiling and
      drying. The proximate composition and beta-carotene content of fresh and
      processed leaves were determined. Amaranth, black nightshade and jute mallow
      leaves had 25.21%, 39.74% and 29.18% of protein, respectively. The beta-carotene
      levels were 16.40, 25.25 and 27.74 mg/100 g for black nightshade amaranth and
      jute mallow leaves, respectively. The ash content was 10.57% for black
      nightshade, 12.40% for jute mallow and 16.33% for amaranth. Processing methods
      caused decreases of beta-carotene and crude lipid content. Boiling for 30 min or
      more resulted in large loss of beta-carotene. Drying under shade resulted in less
      loss of beta-carotene than drying in cabinet at 50 and 60 degrees C.

PMID- 29188042
TI  - Partial characterization of starches from major banana (matooke) cultivars grown
      in Uganda.
AB  - The SEM of starch from five EAHB cultivars showed a mixture of irregular granule
      shapes with smooth surfaces. The starches' average diameter size ranged between
      16.31 and 21.98 MUm. The moisture, protein, and ash content of the starches were:
      11.12%-11.84%, 0.1% and 0.23%-0.47% respectively. The amylose content of these
      starches was between 11% and 13%. The starches peak viscosity ranged between
      488.42 and 558.66 RVU. The EAHB starches exhibited relatively low pasting
      temperatures (<75 degrees C), a high peak viscosity (488.42-558.71 RVU), high
      level of viscosity breakdown (235.00-311.92 RVU) and low set-back values (61.21
      104.33 RVU). In general, the EAHB starches' WHCs and SPs increased substantially
      at 80 degrees C with maximum SP (12.43-14.27 g water/g starch) and solubility
      (12.52%-14.19%) values obtained at 90 degrees C. The starch clarity ranged from
      1.7% to 2.3% and followed the same pattern. The starches exhibited poor freeze
      thaw stability as they had high syneresis (68% to 72%) after 10 freeze-thaw
      cycles.

PMID- 29188043
TI  - Household food insecurity, coping strategies, and nutritional status of pregnant
      women in rural areas of Northern Ghana.
AB  - There is limited information on the magnitude and determinants of household food
      insecurity (HFI) and how it relates to the nutritional status of pregnant women
      in Northern Ghana. The magnitude, determinants of HFI, and how it relates to the
      nutritional status of pregnant women were evaluated in the Africa RISING West
      Africa project intervention communities in Northern Ghana. The prevalence of
      moderate and severe household hunger was 25.9% (95% CI: 19.0, 34.3) and 6.8% (95%
      CI: 4.2, 10.9) respectively. The independent predictors of maternal thinness were
      region of residence, gestational age and maternal age. Compared to women in the
      first trimester, women in the third trimester were 2.2 times more likely of being
      underweight adjusted odds ratio (AOR = 2.19, CI: 1.02, 4.70). Women who were
      under 20 years of age were 11.9 times more likely of being thin compared to women
      aged more than 35 years (AOR = 11.97, CI: 2.55, 5. 67). Food insecurity was
      highly prevalent but it was not associated with maternal thinness of pregnant
      women. The risk of maternal thinness increased as the gestational age increased
      and this has a great potential of adversely influencing pregnancy outcomes and
      overall quality of life.

PMID- 29188044
TI  - Effect of soy protein isolate on the functional, pasting, and sensory
      acceptability of cassava starch-based custard.
AB  - Fortification of custard powder (CP) with protein from cheap sources such as
      soybean could potentially improve its nutritive value but may alter its
      functional and sensory properties. This study was therefore conducted to
      determine the effect of soy protein isolate (SPI) inclusion (0%-20%) on some
      functional and sensory properties of cassava starch-based CP. Functional,
      pasting, and sensory acceptability were determined using standard methods.
      Increase in soy protein isolate significantly (p < .05) decreased dispersibility,
      packed bulk density, swelling power, peak, trough, breakdown, final, and setback
      viscosities, but increased least gelation concentration, water absorption
      capacity, and solubility index. This study further showed that despite increasing
      addition of SPI up to 20%, sensory acceptability of the cassava starch-based CP
      formulations did not differ significantly, and most of them had very similar
      acceptability when compared to that of corn starch-based CP.

PMID- 29188045
TI  - Effects of thermal processing on the nutritional and functional properties of
      defatted conophor nut (Tetracarpidium conophorum) flour and protein isolates.
AB  - Conophor nut (Tetracarpidium conophorum) was processed using different heat
      treatments to explore its full potential as food ingredients. The raw, boiled,
      and toasted nuts were defatted and the proteins isolated by alkaline
      solubilization and isoelectric precipitation. The variously processed nuts were
      analyzed for the proximate and amino acid compositions, and functional
      properties. The protein contents of the isolate ranges between 86.86 g/100g and
      87.74 g/100 g, about 1.5-fold higher than those of the defatted flour samples.
      The essential amino acids of the isolates ranged between 40.57%-41.55%. Glutamic
      acid, aspartic acid, and arginine were the most predominant amino acids, while
      methionine and lysine were the first and second limiting amino acids,
      respectively. The protein efficiency ratio, biological values as well as the
      functional properties of the proteins were improved with processing. These
      properties may enhance the potential use of conophor nut protein isolates as high
      quality protein ingredient in food systems.

PMID- 29188046
TI  - Influence of particle size and extraction solvent on antioxidant properties of
      extracts of tea, ginger, and tea-ginger blend.
AB  - The influence of particle size and extraction solvent on the antioxidant
      properties of aqueous and ethanolic extracts of tea (Camellia sinensis), ginger
      (Zingiber officinale), and tea-ginger (2:1) blend was investigated. The powder
      sizes studied were 0.425, 0.710, and 1.180 mm. Extracts were analyzed for DPPH
      radical scavenging activity, ABTS radical scavenging activity, total phenol
      content (TPC), iron chelating activity, total flavonoid content, and peroxide
      scavenging activity. The powder with the lowest particle size of 0.425 mm tends
      to produce aqueous extracts of tea, ginger, and tea-ginger with highest
      antioxidant content. At this lowest particle size all the antioxidant properties
      assayed were maximized. The TPC of aqueous extracts obtained from the 0.425 mm
      tea, ginger, and tea-ginger powders were 685.44 +/- 175, 283.58 +/- 19, and
      483.02 +/- 176 mg gallic acid equivalent (GAE) L-1, respectively. The TPC of
      aqueous extracts obtained from the 0.710 mm tea, ginger, and tea-ginger powders
      were 679.06 +/- 169, 208.94 +/- 147, and 400.10 +/- 130 mg GAE L-1, respectively.
      However, for the aqueous ethanolic and ethanolic extracts, the particle size that
      maximized the antioxidant extraction varied depending on the antioxidant property
      that was being assayed. The study suggests that particle size influences the
      extraction of antioxidants. Also, the optimum powder size that would maximize
      antioxidant extraction is dependent on the solvent used and the antioxidant
      property being measured.

PMID- 29188047
TI  - Fatty acid profiles of the main lipid classes of green seaweeds from fish pond
      aquaculture.
AB  - The lipid composition of five species of green seaweeds (Chaetomorpha linum,
      Rhizoclonium riparium, Ulva intestinalis, Ulva lactuca, and Ulva prolifera) grown
      in fish pond aquaculture systems was studied. In particular, the overall fatty
      acid (FA) profile and the FA profile of each main lipid class found in these
      seaweed species were thoroughly analyzed. It was found that every seaweed had a
      specific FA profile, whose specificities were rendered more obvious with the
      study of the FA profile per lipid class. However, between U. lactuca and U.
      intestinalis, there were only minor differences. Nonetheless, it was possible to
      identify significant differences between the palmitic acid content in the
      phospholipid (PL) and glycolipid (GL) classes of each seaweed. A clear
      distinction between the FA profiles of R. riparium and C. linum, which belong to
      the Cladophorales order, and those of Ulva genus, Ulvales order, was also
      determined. Moreover, there were also differences among lipid classes, yielding
      large contrasts between PLs + GLs and triacylglycerols (TAGs) as well as between
      monoacylglycerols (MAGs) and free fatty acids (FFAs). This study also found
      evidence supporting the location of particular FAs in specific TAG positions. FA
      profiles have the potential to be used as a chemotaxonomic tool in green
      seaweeds, providing a simple method to check authenticity of seaweed used as
      food.

PMID- 29188048
TI  - Effects of cooking techniques on fatty acid and oxylipin content of farmed
      rainbow trout (Oncorhynchus mykiss).
AB  - The aim of this study was to investigate the effect of various cooking techniques
      on the fatty acid and oxylipin content of farmed rainbow trout. Rainbow trout is
      an excellent source of long-chain omega-3 (n-3) polyunsaturated fatty acids
      (PUFA) which have beneficial health effects. Fillets of 2-year-old farmed rainbow
      trout were baked, broiled, microwaved, or pan-fried in corn (CO), canola (CaO),
      peanut (PO), or high oleic sunflower oil (HOSO). Fatty acids and oxidized lipids
      were extracted from these samples and their respective raw fillet samples. Fatty
      acid content was determined using gas chromatography and oxylipin content by mass
      spectroscopy. The values obtained from each cooking method were compared to those
      obtained from the respective raw fillets using paired t tests. PUFA content was
      not altered when samples were baked, broiled, microwaved, or pan-fried in CO or
      CaO. Pan-frying in PO reduced alpha-linolenic acid (18:3n-3), eicosadienoic acid
      (20:2n-6), and dihomo-gamma-linolenic acid (20:3n-6), while pan-frying in HOSO
      reduced 18:3n-3, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n
      3), docosahexaenoic acid (22:6n-3), linoleic acid (18:2n-6), 18:3n-6, 20:2n-6,
      20:3n-6, docosatrienoic acid (22:2n-6), and adrenic acid (22:4n-6) compared to
      raw fish. Cooking decreased the omega-6 (n-6) PUFA-derived oxylipins, but caused
      no change in 20:5n-3 or 22:6n-3-derived oxylipins of the fillets. In conclusion,
      pan-frying was the only cooking method to alter the fatty acid content of the
      fillets, while observed changes in oxylipin content varied by cooking method. As
      the physiological impact of oxylipins is currently unknown, these results suggest
      that the cooking methods which optimize the consumption of n-3 PUFA from rainbow
      trout are baking, broiling, microwaving, or pan-frying in CO, CaO, or PO.

PMID- 29188049
TI  - Optimization of extrusion conditions for the production of instant grain amaranth
      based porridge flour.
AB  - Malnutrition is one of the foremost causes of death among children below 5 years
      in developing countries. Development of nutrient-dense food formulations using
      locally available crops has been proposed as a means to combat this menace. This
      study optimized the extrusion process for the production of a nutritious amaranth
      based porridge flour. Least cost formulations containing grain amaranth,
      groundnut, iron-rich beans, pumpkin, orange-fleshed sweet potato, carrot, and
      maize were developed and evaluated by a sensory panel (n = 30) for acceptability
      using the 9-point hedonic scale. Extrusion process of the most acceptable
      porridge flour was optimized by response surface methodology (RSM). Barrel
      temperature (130-170 degrees C) and feed moisture content (14%-20%) were the
      independent variables which significantly (p < .05) affected in vitro protein
      digestibility, vitamin A retention, total polyphenol, phytic content, and iron
      and zinc extractabilities. Optimization of the extrusion process improved the
      nutritional quality of the instant flour.

PMID- 29188050
TI  - Effects of household washing on bacterial load and removal of Escherichia coli
      from lettuce and "ready-to-eat" salads.
AB  - Customer demands for fresh salads are increasing, but leafy green vegetables have
      also been linked to food-borne illness due to pathogens such as Escherichia coli
      O157:H7. As a safety measure, consumers often wash leafy vegetables in water
      before consumption. In this study, we analyzed the efficiency of household
      washing to reduce the bacterial content. Romaine lettuce and ready-to-eat mixed
      salad were washed several times in flowing water at different rates and by
      immersing the leaves in water. Lettuce was also inoculated with E. coli before
      washing. Only washing in a high flow rate (8 L/min) resulted in statistically
      significant reductions (p < .05), "Total aerobic count" was reduced by 80%, and
      Enterobacteriaceae count was reduced by 68% after the first rinse. The number of
      contaminating E. coli was not significantly reduced. The dominating part of the
      culturable microbiota of the washed lettuce was identified by rRNA 16S sequencing
      of randomly picked colonies. The majority belonged to Pseudomonadaceae, but
      isolates from Enterobacteriaceae and Staphylococcaceaceae were also frequently
      found. This study shows the inefficiency of tap water washing methods available
      for the consumer when it comes to removal of bacteria from lettuce. Even after
      washing, the lettuce contained high levels of bacteria that in a high dose and
      under certain circumstances may constitute a health risk.

PMID- 29188051
TI  - The science behind autologous fat grafting.
AB  - Introduction: Adipose grafting has undergone significant changes over time. Many
      different techniques have been followed by trying to improve the quality of the
      lipoaspirate and the survival of the fat graft after implantation. Material and
      methods: The purpose of this review is to analyse the historical evolution of the
      surgical harvesting and implant technique, describing the changes that have
      brought significant improvements, revolutionizing the aesthetic and functional
      results obtainable. Results: A standard fat grafting technique is commonly
      performed in three stages: harvesting of adipose tissue from a suitable donor
      site; processing of the lipoaspirate to eliminate cellular debris, acellular oil
      and excess of infiltrated solution, reinjection of the purified adipose tissue.
      The most widely used surgical technique was described by Coleman. He modified and
      corrected the methods and results of his predecessors and proposed an atraumatic
      protocol for the treatment of adipose tissue.He reported that the key to
      successful fat grafting lies in the technique. In addition, he noticed that
      adipose tissue was not only a good filler, but improved the quality of the skin.
      In fact, fat grafts demonstrated to have not only dermal filler properties but
      also regenerative potential owing to the presence of stem cells in fat tissue.
      Conclusion: Adipose tissue, actually, is the closest to the ideal filler because
      it is readily available; easily obtainable, with low donor-site morbidity;
      repeatable; inexpensive; versatile; and biocompatible. There is an abundance of
      literature supporting the efficacy of fat grafting in both aesthetic and
      reconstructive cases. Recent studies have shown the utility of adipose-derived
      stem cells in the improvement of wound healing, describing their ability to
      regenerate soft tissues and their remodelling capacity provided by their unique
      cytokine and growth factor profiles.Despite ongoing concerns about survival and
      longevity of fat grafts after implantation and unpredictability of long-term
      outcome, fat has been successfully used as a filler in many differ clinic
      situation.

PMID- 29188052
TI  - Biological roles of hepatocyte growth factor-Met signaling from genetically
      modified animals.
AB  - Hepatocyte growth factor (HGF) is produced by stromal and mesenchymal cells, and
      it stimulates epithelial cell proliferation, motility, morphogenesis and
      angiogenesis in various organs via tyrosine phosphorylation of its cognate
      receptor, Met. The HGF-Met signaling pathway contributes in a paracrine manner to
      the development of epithelial organs, exerts regenerative effects on the
      epithelium, and promotes the regression of fibrosis in numerous organs.
      Additionally, the HGF-Met signaling pathway is correlated with the biology of
      cancer types, neurons and immunity. In vivo analyses using genetic modification
      have markedly increased the profound understanding of the HGF-Met system in basic
      biology and its clinical applications. HGF and Met knockout (KO) mice are
      embryonically lethal. Therefore, amino acids in multifunctional docking sites of
      Met have been exchanged with specific binding motifs for downstream adaptor
      molecules in order to investigate the signaling potential of the HGF-Met
      signaling pathway. Conditional Met KO mice were generated using Cre-loxP
      methodology and characterization of these mice indicated that the HGF-Met
      signaling pathway is essential in regeneration, protection, and homeostasis in
      various tissue types and cells. Furthermore, the results of studies using HGF
      overexpressing mice have indicated the therapeutic potential of HGF for various
      types of disease and injury. In the present review, the phenotypes of Met gene
      modified mice are summarized.

PMID- 29188053
TI  - Ex vivo regenerative effects of a spring water.
AB  - Previous experiments by our group have indicated the regenerative effects of a
      spring water (Comano), which was possibly associated with the native non
      pathogenic bacterial flora. The present study aimed to confirm these regenerative
      properties in a human ex vivo experimental model in the context of physiological
      wound healing. Human 6-mm punch skin biopsies harvested during plastic surgery
      sessions were injured in their central portion to induce skin loss and were
      cultured in either conventional medium (controls) or medium powder reconstituted
      with filtered Comano spring water (treated samples). At 24, 48 and 72 h the
      specimens were observed following staining with hematoxylin and eosin,
      Picrosirius Red, orcein and anti-proliferating cell nuclear antigen. Compared
      with the controls, the treated samples exhibited reduced overall cell
      infiltration, evidence of fibroblasts, stimulation of cell proliferation and
      collagen and elastic fiber regeneration. In the spring water, in addition to 12
      resident non-pathogenic bacterial strains exhibiting favorable metabolic
      activities, more unknown non-pathogenic species are being identified by genomic
      analysis. In the present study, the efficacy of this 'germ-free', filtered spring
      water in wound regeneration was indicated. Thus, the Comano spring water
      microbiota should be acknowledged for its regenerative properties.

PMID- 29188054
TI  - Solitary pulmonary capillary hemangioma presents as ground glass opacity on
      computed tomography indicating adenocarcinoma in situ/atypical adenomatous
      hyperplasia: A case report.
AB  - Solitary pulmonary capillary hemangioma (SPCH) is a rare type of benign lung
      tumor, which must be distinguished from early lung cancer and precancerous
      lesions of the lung that manifest in a similar way upon imaging. The current
      study describes a case of SPCH and a review of the literature is performed. The
      patient was a 40-year-old Chinese woman who was referred to the Liaoning Cancer
      Hospital and Institute (Shenyang, China) in October, 2015 with a cough without
      obvious inducement. Computed tomography (CT) demonstrated pure ground glass
      opacity (GGO) in the right upper lung. Following systemic anti-inflammatory
      therapy over 6 months, the lesion did not exhibit any change on CT and was
      suspected to be an adenocarcinoma in situ (AIS) or atypical adenomatous
      hyperplasia (AAH). Video-assisted thoracic surgery wedge resection was
      subsequently performed. Frozen section diagnosis revealed a benign tumor without
      atypical epithelial cells. Subsequent to surgery, paraffin sections demonstrated
      that the tumor contained narrow alveolar cavities, thickened alveolar septa and a
      clear boundary separating it from healthy lung tissue. Furthermore, the
      proliferation lumens in the alveolar septa were lined with a single layer of flat
      cells. Immunohistochemical staining revealed that the flat cells were positive
      for cluster of differentiation CD31 and CD34, and negative for thyroid
      transcription factor-1 and cytokeratin. The proliferation of capillary vessels
      lead to the thickened alveolar septa and the tumor was diagnosed as SPCH. When
      imaging examination demonstrates a GGO in lung, SPCH must be considered in the
      differential diagnosis of AIS/AAH. As the prognosis of these lesions is entirely
      different, a pathological examination must be conducted to ensure a correct
      diagnosis.

PMID- 29188055
TI  - Aberrant expression of interleukin-10 and activation-induced cytidine deaminase
      in B cells from patients with Behcet's disease.
AB  - Despite extensive studies, the pathogenesis of Behcet's disease (BD) remains
      unclear. In particular, the roles of B cells in patients with BD have not been
      elucidated. Activation-induced cytidine deaminase (AID) is a critical enzyme for
      immunoglobulin (Ig) heavy chain class switching and somatic hypermutation in B
      cells and the abnormal expression of AID in various immune conditions has
      previously been studied. B10 cells, an interleukin (IL)-10-secreting subset of
      regulatory B cells, function to downregulate inflammation and autoimmunity. Thus,
      in the present study, the relevance of B cells in patients with BD was
      investigated. The plasma levels of IL-10 and IgA and the proportions of cluster
      of differentiation (CD)43+ B cells, excluding naive B cells, were measured in 16
      patients with BD and 16 age- and sex-matched healthy controls (HCs).
      Additionally, the mRNA levels of IL-10 and AID were assessed in B cells from
      fresh peripheral blood samples of the BD patients and HCs. The plasma level of IL
      10 in patients with BD did not differ significantly from that in HCs. Similarly,
      there was no significant difference in the plasma level of IgA, although a slight
      increase was observed in patients with BD compared with that in HCs. There were
      no differences in CD43+CD19+ B cell numbers between patients with BD and HCs.
      However, IL-10 mRNA levels were significantly reduced (P<0.05), while AID mRNA
      levels were significantly increased (P<0.01) in the B cells of patients with BD
      compared with those in HCs. These results provide insight into the role of B
      cells in patients with BD.

PMID- 29188056
TI  - Molecular cloning, expression, purification and functional characterization of an
      antifungal cyclophilin protein from Panax ginseng.
AB  - Cyclophilins (CyPs), a member of peptidyl-prolyl cis-trans isomerases (PPIases),
      are ubiquitously distributed in organisms such as bacteria, yeast, plants and
      animals. CyPs have diverse biological functions, with some exhibiting antifungal
      and antiviral activities. In this study, Panax ginseng cyclophilin (pgCyP), a
      novel gene encoding an antifungal protein from Panax ginseng, was cloned, and its
      protein product was expressed in Escherichia coli, and then fractionated by
      affinity chromatography. The open reading frame of the pgCyP full-length coding
      sequence was found to encode a single-domain CyP-like protein of 174 amino
      residues with a calculated molecular weight of 18.7 kDa. The pGEX system was used
      to express pgCyP fused to glutathione S-transferase. After affinity purification,
      the protein showed a strong fungal resistance effect on Phytophthora cactorum. In
      addition, pgCyP showed high PPIase activity. To the best of our knowledge, the
      present study is the first successful effort to clone and characterize a CyP-like
      protein gene from Panax ginseng.

PMID- 29188057
TI  - Subungual onychomycosis due to Aspergillus niger mimicking a glomus tumor: A case
      report.
AB  - Onychomycosis is a common nail infection caused by dermatophytes, while non
      dermatophytes including Aspergillus spp. are causes of nail onychomycosis.
      Aspergillus niger is not common as a cause of nail onychomycosis. In the current
      study we present a 60-year-old woman with subungual onychomycosis due to
      Aspergillus niger mimicking a glomus tumor. Physical examination revealed right
      thumb had a black color of nail bed. Localized tenderness and severe pain were
      observed. However, the cold sensitivity test, Loves pin test and Hildreths test
      were negative. On radiograph, bone erosion was found in a part of distal phalanx
      at the right thumb. Magnetic resonance imaging identified a mass at the subungual
      space, which exhibited low signal intensity on T1-weighted images and high signal
      intensity on T2-weighted images. The differential diagnosis included glomus tumor
      and infection. The histological findings demonstrated dichotomous septate hyphae.
      The culture was positive for Aspergillus niger. The results suggested that when
      physical examination is not typical for a glomus tumor, other diseases may be
      considered. Additionally, frozen section diagnosis may be useful.

PMID- 29188058
TI  - Alterations in three biomarkers (estrogen receptor, progesterone receptor and
      human epidermal growth factor 2) and the Ki67 index between primary and
      metastatic breast cancer lesions.
AB  - In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor
      (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2)
      status, occasionally changes. This change, in addition to the Ki67 index were
      evaluated at sites of recurrence and the correlation between changes in tumor
      phenotype and survival were assessed in breast cancer patients. Comparisons in
      pathological parameters between primary and metastatic lesions were drawn between
      ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The
      association between changes in tumor phenotype and patient survival was assessed.
      The hormone receptor status changed from positive, in the primary lesions, to
      negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients,
      respectively. Conversion from negative to positive status was confirmed in 27.2%
      (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from
      negative (primary lesion) to positive (metastatic lesion) occurred in seven
      patients (10%). The mean Ki67 index of primary lesions with positive hormone
      receptor status was significantly lower than at sites of recurrence with any
      hormone receptor status, from 10.9+/-9.8 standard deviation (SD) to 22.9+/-18.6
      (P=0.031) and 12.2+/-10.5 SD to 27.4+/-20.9 (P=0.023), for ER and PR,
      respectively. The mean overall survival of patients with ER status conversion
      from positive to negative was 7.4+/-1.2 standard error (SE) years, and 14.8+/-1.4
      SE years for patients who retained positive ER status (P=0.005, log-rank), with a
      hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in
      survival based upon change in ER status was similarly observed in patients with
      PR status conversion in the same direction. Thus, ER and PR status conversion at
      the time of recurrence strongly impact survival, particularly if the change is
      from positive (primary lesion) to negative (metastatic lesion). Monitoring the
      biological behavior of breast cancer may benefit a patient by allowing for a
      novel personalized treatment strategy.

PMID- 29188059
TI  - Efficacy of high dose vitamin D supplementation in improving serum 25
      hydroxyvitamin D among laboratory personnel working at the Nepal National Center
      for Rheumatic Diseases.
AB  - Vitamin D deficiency is a highly prevalent condition worldwide. However, few
      studies have been conducted to examine the vitamin D status of laboratory
      personnel and the correlation between vitamin D deficiency and working
      conditions. The aim of the present study was to assess changes in serum 25
      hydroxyvitamin D [25(OH)D] concentration with a weekly dose of oral
      cholecalciferol (60,000 IU) for two months. The prospective, open-label,
      interventional study was conducted from January 2016 to March 2016 at the
      National Centre for Rheumatic Diseases, Kathmandu, Nepal. The serum level of
      25(OH)D in 19 healthy laboratory volunteers was measured at baseline and
      following the 2-month regimen with cholecalciferol supplement at 60,000 IU (1,500
      ug)/week in oral tablet form. At baseline the mean serum 25(OH)D level was
      10.31+/-7.78 ng/ml, which was increased following completion of the course of
      oral cholecalciferol to 59.78+/-14.74 ng/ml. This difference in the mean serum
      level of 25(OH)D compared with baseline was significant to P<0.001. These results
      indicate that vitamin D deficiency is prevalent among laboratory workers, and
      that high dose vitamin D3 (60,000 IU cholecalciferol) in tablet form may be
      effective in achieving sufficient serum 25(OH)D among laboratory personnel who
      tend to have lower baseline serum 25(OH)D. In conclusion, vitamin D deficiency
      may be common among laboratory workers, and guidelines should be formulated to
      implement vitamin D supplementation among laboratory personnel, as well as indoor
      workers, in Nepal.

PMID- 29188060
TI  - Effects of MPO-463G/A and -129G/A polymorphisms on coronary artery disease risk
      and patient survival in a Turkish population.
AB  - Myeloperoxidase (MPO) is an oxidative hemoprotein compound expressed in
      polymorphonuclear leukocytes that contributes to inflammatory responses. Coronary
      artery disease (CAD), as the most prevalent form of heart disease, is considered
      to originate from an interaction between genetic and environmental factors. In
      the present study, the potential associations between MPO-463G/A and -129G/A
      polymorphisms with CAD were investigated in a Turkish population using a
      polymerase chain reaction-based restriction fragment length polymorphism (RFLP)
      assay technique. To the best of our knowledge, the study was the first to examine
      the association of MPO-463G/A and -129G/A with patient survival rate in a Turkish
      population. The study population consisted of 201 patients with CAD and 201
      healthy controls. The results indicated that there was a significant association
      of the GA genotype of MPO-463G/A with the case population (P=0.048). Meanwhile,
      in the patients with CAD, the frequency distributions of the MPO-129A allele
      (P=0.006) and GA genotype (P=0.001) were significantly increased compared with
      the G allele and GG genotype, respectively, in CAD patients. Additionally,
      compared with the GG genotype, the frequency distribution of MPO-129A was
      significantly increased in the patient group regarding smoking status (P=0.001)
      and the presence of hypercholesterolemia (P=0.028). However, survival analysis
      did not detect an effect of either polymorphism on the survival rate of the CAD
      patients (P>0.05). Therefore, the MPO-129GA genotype may be a significant risk
      factor for the development of CAD.

PMID- 29188061
TI  - Effect of Coriolus versicolor glucan on the stimulation of cytokine production in
      sarcoma-180-bearing mice.
AB  - Coriolus versicolor (CV) contains high levels of bioactive compounds, including
      the glucan (1->6)-alpha-D-glucopyranosyl. However, there is a lack of data
      regarding the potential effect of this CV glucan (CVG) on the stimulation of
      cytokine production. The present study evaluated the effect of CVG on the
      stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated
      with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after
      which serum levels of cytokines, namely interleukin (IL)-2, -4, -6, -10, -17A and
      interferon (IFN)-alpha and -gamma, were investigated by ELISA. CVG significantly
      promoted the secretion of IL-2, -4, -6, -10, -17A and IFN-alpha and -gamma at the
      doses of 100 (P<0.05) and 200 (P<0.01) mg/kg, but not at 40 mg/kg (P>0.05), when
      compared with cyclophosphamide treatment, as a positive control. Additionally,
      cytokine production associated with T helper (Th)2 and Th17 cells was enhanced
      compared with that of Th1 cytokines, and the immunomodulatory function of CVG
      appeared to be IL-10-dependent. These results demonstrate that CVG may stimulate
      the production of cytokines and serve as a Th2/IL-10-dependent immunomodulator,
      and thus has promise in supporting cancer therapies.

PMID- 29188064
TI  - "Streptomyces massilialgeriensis" sp. nov., a new bacterial species isolated from
      an extremely saline soil collected from the dry lake of Ank el Djamel in Algeria.
AB  - We report here the main characteristics of "Streptomyces massilialgeriensis"
      strain S35T (CSUR = P3927), a new bacterial species within the Streptomyces
      genus, isolated from an extremely saline soil sample collected from the site of
      Garaet Ank Djemel in the Wilaya of Oum El Bouaghi, Algeria.

PMID- 29188062
TI  - Human aqueous humor levels of transforming growth factor-beta2: Association with
      matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases.
AB  - The present study aims to investigate the association of transforming growth
      factor-beta2 (TGF-beta2) and matrix metalloproteinases (MMPs), MMP-2 and MMP-3,
      and tissue inhibitors of matrix metalloproteinases (TIMPs), TIMP-1, TIMP-2 and
      TIMP-3 in the aqueous humor of patients with high myopia or cataracts. The levels
      of TGF-beta2 and MMPs/TIMPs were measured with the Luminex xMAP Technology using
      commercially available Milliplex xMAP kits. The association between TGF-beta2 and
      MMPs/TIMPs levels was analyzed using the Spearmans correlation test. The levels
      of TGF-beta2 were identified to be positively correlated with the levels of TIMP
      1 and TIMP-3 (TIMP-1: r=0.334; P=0.007; TIMP-3: r=0.309; P=0.012). The levels of
      MMP-2, MMP-3 and TIMP-2 did not significantly correlate with TGF-beta2 levels
      (P>0.05). A positive correlation was identified between TGF-beta2 and TIMPs in
      the aqueous humor of human eyes with elongated axial length. It appears that TGF
      beta2 stimulates the expression of TIMPs as a compensatory reaction to the
      development of high myopia.

PMID- 29188063
TI  - High rates of nontuberculous mycobacteria isolation from patients with
      presumptive tuberculosis in Iran.
AB  - Nontuberculous mycobacteria (NTM) can cause disease which can be
      indistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic
      challenge, particularly in low- and middle-income settings. We aimed to
      investigate the mycobacterial agents associated with presumptive clinical
      pulmonary TB in Iran. A total of 410 mycobacterial isolates, obtained between
      March 2014 and January 2016, from 7600 clinical samples taken from consecutive
      cases of presumptive diagnosis of TB were identified. Phenotypic and molecular
      tests were used to identify the isolated organisms to the species level. Single
      locus and multilocus sequence analysis based on 16S rRNA, rpoB, hsp65 and ITS
      locus were used to confirm the results. Of 410 consecutive strains isolated from
      suspected TB subjects, 62 isolates (15.1%) were identified as NTM. Patients with
      positive NTM cultures met American Thoracic Society diagnostic criteria for NTM
      disease. Mycobacterium simiae was the most frequently encountered (38.7%),
      followed by Mycobacterium fortuitum (19.3%), M. kansasii (17.7%) and M. avium
      complex (8.0%). Isolation of NTM, including M. simiae, from suspected TB cases is
      a serious public health problem and merits further attention by health
      authorities, physicians and microbiologists.

PMID- 29188065
TI  - High circulating plasma dipeptidyl peptidase- 4 levels in non-obese Asian Indians
      with type 2 diabetes correlate with fasting insulin and LDL-C levels, triceps
      skinfolds, total intra-abdominal adipose tissue volume and presence of diabetes:
      a case-control study.
AB  - Aim: To evaluate circulating plasma dipeptidyl peptidase-4 (DPP4) levels in non
      obese Asian Indians with type 2 diabetes mellitus (T2DM), and to correlate these
      with metabolic profile and measures of anthropometry, skinfolds, abdominal
      adipose tissue depots, pancreatic volume, and liver span. Methodology: Non-obese
      (body mass index (BMI) <25 kg/m2) patients with T2DM (cases, n=93), diagnosed
      within 1 year from recruitment, on metformin therapy and BMI-matched, and non
      diabetic subjects (controls, n=40) were compared. Measurements of blood glucose,
      glycosylated hemoglobin, plasma insulin levels, lipid profile, hepatic
      transaminases and plasma DPP4 levels, and quantification of abdominal fat depots,
      pancreatic volume and liver span (MRI scan), were done. Results: Significantly
      higher (p<0.001) circulating plasma DPP4 levels were observed in cases as
      compared to controls. Specifically, in patients with T2DM with non-alcoholic
      fatty liver disease (NAFLD) (n=48), the mean plasma DPP4 level (52.6+/-27.8
      ng/mL) was significantly higher (p<0.05) as compared with those without NAFLD
      (n=43; 47+/-28.3 ng/mL). Significant positive correlation was observed for
      circulating plasma DPP4 levels with waist-to-hip ratio, total intra-abdominal
      adipose volume, and liver span. Fasting serum insulin, low-density lipoprotein
      cholesterol (LDL-C), triceps skinfolds, total intra-abdominal adipose tissue
      volume and presence of T2DM were significant determinants of circulating plasma
      DPP4 levels. Conclusion: Non-obese Asian Indian patients with T2DM and on
      metformin therapy have significantly higher circulating plasma DPP4 levels as
      compared to non-obese non-diabetic controls, and these levels correlate with
      fasting insulin and LDL-C levels, upper limb subcutaneous adipose tissue, intra
      abdominal adiposity and presence of diabetes.

PMID- 29188066
TI  - Aeromonas wound infection in a healthy boy, and wound healing with polarized
      light.
AB  - Introduction. At emergency departments, history taking is often very brief. We
      present a case of an Aeromonas wound infection, that illustrates the importance
      of careful history taking. We also report the first successful use of polarized
      light as additional therapy for healing of this infectious wound. Case
      presentation. A healthy boy was diagnosed with a wound infection, after a fall
      onto rocks. At first, it remained unmentioned that there had been contact with
      ditchwater, so he was treated with amoxicillin-clavulanic acid. Only after the
      finding of an Aeromonas strain in the wound culture, and treatment with a
      fluoroquinolone, did he recover. Wound healing was aided with the use of
      polarized light, and with good effect. To our knowledge, this is the first report
      on the effect of polarized light on the healing of infectious wounds. Conclusion.
      Careful history taking is essential for adequate empiric therapy when faced with
      wounds and wound infections. Aeromonas infections are associated with water
      exposure, and should be treated with fluoroquinolones. Polarized light seems to
      have a good result on healing of infectious wounds.

PMID- 29188067
TI  - Isolation and characterization of Leptospira interrogans serovar Copenhageni from
      a dog from Saint Kitts.
AB  - Introduction. Leptospirosis is a zoonotic bacterial disease of global
      distribution affecting humans and animals. The initial phase of leptospirosis
      resembles many other febrile illness and due to its broad and biphasic clinical
      manifestations, selection and implementation of appropriate diagnostic tests can
      be challenging. Case presentation. This report describes a case investigation of
      a 14 weeks old male, orphan puppy, presented with generalised jaundice, anemia,
      weakness, and anorexia. Clinical abnormalities included the evidence of renal and
      hepatic failure. Antemortem and postmortem diagnostic investigations were
      conducted to identify the cause of illness. PCR testing and culture of blood was
      positive for Leptospira sp. Necropsy followed by histopathology evaluation
      revealed lesions compatible with liver and kidney damage consisting of marked
      diffuse hepatocellular dissociation, acute renal tubular necrosis, and mild
      interstitial nephritis. Conclusion. Multiple diagnostic techniques including
      bacterial isolation confirmed Leptospira infection in this puppy. Whole genome
      sequencing and analysis identified the Leptospira sp. isolated from this puppy as
      Leptospira interrogans serovar Copenhageni. To our knowledge, this case report
      describes the first isolation of Leptospira from Saint Kitts. This case
      highlights the usefulness of including multiple diagnostic tests for the
      diagnosis and epidemiological investigation of Leptospira infection. Accurate
      diagnosis followed by timely intervention can prevent case fatality and mortality
      in infected patients.

PMID- 29188068
TI  - 32-week premature rupture of membranes caused by oropharyngeal microbiota.
AB  - Introduction. Preterm premature rupture of membranes (PPROM) usually has a
      multifactorial etiology that is often unknown, although the most frequently
      reported cause is infection by group B Streptococcus. Therefore, the etiology of
      PPROM, although probably infectious, remains unknown in most cases. This case
      describes a PPROM caused by infection from oropharyngeal microbiota. Case
      presentation. We report the case of a 26-yr-old pregnant woman. The gestational
      age was 32 weeks+5 days. Examinations in the emergency department revealed the
      release of clear amniotic fluid and a closed multiparous cervix with a length of
      22 mm. Endocervical culture evidenced the growth of Staphylococcus aureus,
      serogroup B Neisseria meningitidis and Haemophilus influenzae. Conclusion.
      Preventive antibiotic therapy should consider: opportunistic infections by normal
      genital microbiota, infections due to sexual activity, opportunist microorganisms
      derived from oral sex, and the hematogenous spread of oral bacteria.

PMID- 29188069
TI  - Simultaneous isolation of Chryseobacterium gleum from bloodstream and respiratory
      tract: first case report from India.
AB  - Introduction. Species of the genus Chryseobacterium are emerging healthcare
      associated pathogens, often colonizing the hospital environment. There are no
      clear guidelines available for antimicrobial susceptibility of this organism. In
      this report we present the first case, to our knowledge, of simultaneous central
      line-associated bloodstream infection (CLABSI) and ventilator-associated
      pneumonia (VAP) due to Chryseobacterium gleum from India. Case presentation. A 62
      years old man with a history of a road traffic accident 1 month previously was
      referred to our center for further management. He developed features of sepsis
      and aspiration pneumonia on day 3 of admission. Four blood cultures (two each
      from central and peripheral lines) and two tracheal aspirate cultures grew pure
      yellow colonies of bacteria. Both matrix assisted laser desorption ionization
      time of flight mass spectrometry, (MALDI-TOF MS; bioMerieux, Marcy-L'Etoile,
      France,) and BD Phoenix (BD Biosciences, Maryland, USA) identified the organism
      as C. gleum. However, BD Phoenix failed to provide MIC breakpoints. The isolates
      of C. gleum both from blood and tracheal aspirate showed identical susceptibility
      patterns: resistant to cephalosporins and carbapenems and susceptible to
      ciprofloxacin, levofloxacin, amikacin, trimethoprim+sulfamethoxazole,
      piperacillin-tazobactam, cefoperazone-sulbactam, doxycycline, minocycline and
      vancomycin. Following levofloxacin therapy, the fever responded within 48 h and
      procalcitonin levels decreased without removal of the central line or
      endotracheal tube. However, the patient developed sudden cardiac arrest on day 10
      of treatment and could not be resuscitated. Conclusion. Rapid and accurate
      identification of C. gleum in the laboratory, preferably based on MALDI-TOF, is
      essential for guiding therapy. C. gleum responds well to fluoroquinolones without
      the need to remove indwelling catheters.

PMID- 29188070
TI  - The first case report of septic abortion resulting from beta-lactamase-negative
      ampicillin-resistant non-typeable Haemophilus influenzae infection.
AB  - Introduction. This is the first case report of septic abortion due to beta
      lactamase-negative ampicillin-resistant (BLNAR) non-typeable Haemophilus
      influenzae infection. In Japan, BLNAR H. influenzae is widespread and has become
      a clinical concern, especially in paediatrics and otolaryngology, but H.
      influenzae has not been previously recognized as a causative agent of obstetric
      or gynaecological infection. Case presentation. A 31-year-old pregnant woman
      presented at 17 weeks and 6 days of gestation with a high fever; she was admitted
      with a diagnosis of threatened premature delivery. Despite tocolytic treatment,
      she aborted spontaneously 2 h after admission and then entered septic shock.
      BLNAR H. influenzae was detected in both blood and vaginal cultures. Her
      condition gradually improved after several days of treatment with cefotaxime, and
      she was ultimately discharged without sequelae or complaints. Conclusion.
      Although penicillin with a beta-lactamase inhibitor is currently recommended for
      the treatment of septic abortion, this combination will probably lead to
      treatment failure in the case of BLNAR H. influenzae infection. As this study
      reveals, H. influenzae can cause septic abortion; hence, future efforts should be
      undertaken to detect and therapeutically target this pathogen during pregnancy.

PMID- 29188071
TI  - Postoperative Tropheryma whipplei endophthalmitis - a case report highlighting
      the additive value of molecular testing.
AB  - Introduction.Tropheryma whipplei is the causative agent of Whipple's disease.
      Gastrointestinal and lymphatic tissues are affected in the majority of cases,
      resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of
      ocular manifestation in a patient lacking the typical Whipple symptoms. Case
      presentation. A 74-year-old Caucasian female presented with blurred vision in the
      right eye over a period of 1-2 months, accompanied by stinging pain and
      conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was
      hand motion in the affected eye. Ophthalmological examination showed typical
      signs of intraocular inflammation. Diagnostic and therapeutic pars plana
      vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin
      and amikacin was performed within hours of initial presentation. Both microscopic
      analysis and microbial cultures of the vitreous biopsy remained negative for
      bacteria and fungi. The postoperative antibiotic regime included intravenous
      administration of ceftriaxone in combination with topical tobramycin and
      ofloxacin. Due to the empirical therapy the inflammation ceased and the patient
      was discharged after 5 days with cefpodoxime orally and local antibiotic and
      steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for
      the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the
      PCR product revealed a specific sequence of T. whipplei. Conclusion. In our
      patient, endophthalmitis was the first and only symptom of Morbus Whipple, while
      most patients with Whipple's disease suffer from severe gastrointestinal
      symptoms. 16S rDNA PCR should be considered for any intraocular infection when
      microscopy and standard culture methods remain negative.

PMID- 29188072
TI  - Systemic Rasamsonia piperina infection in a German shepherd cross dog.
AB  - Introduction. Infection with the Rasamsonia argillacea species complex represents
      an emerging problem in human and veterinary medicine with systemic mycoses
      presenting with significant clinical complications and being a cause of death.
      Case presentation. In this report, a case of systemic Rasamsonia piperina
      infection discovered in a 3-year-old male neutered, German shepherd cross dog is
      described together with the clinical presentation, the course of the disease and
      diagnosis. This report describes the first case of veterinary mycosis due to R.
      piperina in Europe and the first case in humans or animals in the UK. Conclusion.
      Although seemingly rare, R. argillacea species complex infection should be a
      differential diagnosis for dogs, especially German shepherds with the described
      presenting signs, and radiographic and ultrasonographic findings.

PMID- 29188073
TI  - Osteopontin is associated with disease severity and antiphospholipid syndrome in
      well characterised Swedish cases of SLE.
AB  - Objective: The variety of disease phenotypes among patients with SLE challenges
      the identification of new biomarkers reflecting disease activity and/or organ
      damage. Osteopontin (OPN) is an extracellular matrix protein with
      immunomodulating properties. Although raised levels have been reported, the
      pathogenic implications and clinical utility of OPN as a biomarker in SLE are far
      from clear. Thus, the aim of this study was to characterise OPN in SLE. Methods:
      Sera from 240 well-characterised adult SLE cases classified according to the
      American College of Rheumatology (ACR) and/or the Systemic Lupus International
      Collaborating Clinics (SLICC) criteria, and 240 population-based controls were
      immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used
      to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect
      damage accrual. Results: Serum OPN levels were in average raised fourfold in SLE
      cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K,
      especially in patients with a disease duration of <12 months (r=0.666, p=0.028).
      OPN was highly associated with SDI (p<0.0001), especially in the renal
      (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally,
      OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both
      clinical and laboratory criteria of APS had significant positive impact on OPN
      levels. Conclusions: In this cross-sectional study, circulating OPN correlates
      with disease activity in recent-onset SLE, reflects global organ damage and
      associates with APS. Longitudinal studies to dissect whether serum OPN also
      precedes and predicts future organ damage are most warranted.

PMID- 29188074
TI  - Heads-up 3D vision system for retinal detachment surgery.
AB  - Here we present procedural and safety results from our initial experience using
      3D heads-up vitrectomy for retinal detachment surgery. The comparison with our
      outcomes from previous standard surgery shows how the new 3D system seems safe
      and effective.

PMID- 29188075
TI  - Targeting muscle stem cell intrinsic defects to treat Duchenne muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a genetic disease characterised by skeletal
      muscle degeneration and progressive muscle wasting, which is caused by loss-of
      function mutations in the DMD gene that encodes for the protein dystrophin.
      Dystrophin has critical roles in myofiber stability and integrity by connecting
      the actin cytoskeleton to the extracellular matrix. Absence of dystrophin leads
      to myofiber fragility and contributes to skeletal muscle degeneration in DMD
      patients, however, accumulating evidence also indicate that muscle stem cells
      (also known as satellite cells) are defective in dystrophic muscles, which leads
      to impaired muscle regeneration. Our recent work demonstrated that dystrophin is
      expressed in activated satellite cells, where it regulates the establishment of
      satellite cell polarity and asymmetric cell division. These findings indicate
      that dystrophin-deficient satellite cells have intrinsic dysfunctions that
      contribute to muscle wasting and progression of the disease. This discovery
      suggests that satellite cells could be targeted to treat DMD. Here we discuss how
      these new findings affect regenerative therapies for muscular dystrophies.
      Therapies targeting satellite cells hold great potential and could have long-term
      efficiency owing to the high self-renewal ability of these cells.

PMID- 29188076
TI  - Epithelial-to-mesenchymal transition in gallbladder cancer: from clinical
      evidence to cellular regulatory networks.
AB  - Gallbladder cancer (GBC), with late diagnosis, rapid disease progression and
      early metastasis, is a highly aggressive malignant tumor found worldwide.
      Patients with GBC have poor survival, low curative resection rates and early
      recurrence. For such a lethal tumor, uncovering the mechanisms and exploring new
      strategies to prevent tumor progression and metastasis are critically important.
      Epithelial-to-mesenchymal transition (EMT) has a prominent role in the early
      steps of tumor progression and metastasis by initiating polarized epithelial cell
      transition into motile mesenchymal cells. Accumulating evidence suggests that EMT
      can be modulated by the cooperation of multiple mechanisms affecting common
      targets. Signaling pathways, transcriptional and post-transcriptional regulation
      and epigenetic alterations are involved in the stepwise EMT regulatory network in
      GBC. Loss of epithelial markers, acquisition of mesenchymal markers and
      dysregulation of EMT-inducing transcription factors (EMT-TFs) have been observed
      and are associated with the clinicopathology and prognosis of GBC patients.
      Therefore, EMT may be a detectable and predictable event for predicting GBC
      progression and metastasis in the clinic. In this review, we will provide an
      overview of EMT from the clinical evidence to cellular regulatory networks that
      have been studied thus far in clinical and basic GBC studies.

PMID- 29188078
TI  - One-shot Synesthesia.
AB  - Synesthesia is commonly thought to be a phenomenon of fixed associations between
      an outside inducer and a vivid concurrent experience. Hence, it has been proposed
      that synesthesia occurs due to additional connections in the brain with which
      synesthetes are born. Here we show that synesthesia can be a much richer and more
      flexible phenomenon with a capability to creatively construct novel synesthetic
      experiences as events unfold in people's lives. We describe here cases of
      synesthetes who occasionally generate novel synesthetic experience, called one
      shot synesthesias. These synesthetic experiences seem to share all the properties
      with the classical synesthetic associations except that they occur extremely
      rarely, people recalling only a few events over the lifetime. It appears that
      these one-shots are not created at random but are instead responses to specific
      life events. We contrast the properties of those rare synesthetic events with
      other, more commonly known forms of synesthesia that also create novel
      synesthetic experiences, but at a high rate-sometimes creating novel experiences
      every few seconds. We argue that one-shot synesthesias indicate that synesthetic
      associations are by their nature not prewired at birth but are dynamically
      constructed through mental operations and according to the needs of a synesthetic
      mind. Our conclusions have implications for understanding the biological
      underpinnings of synesthesia and the role the phenomenon plays in the lives of
      people endowed with synesthetic capacities.

PMID- 29188077
TI  - Orai1, 2, 3 and STIM1 promote store-operated calcium entry in pulmonary arterial
      smooth muscle cells.
AB  - Previous studies have demonstrated that besides the classic canonical transient
      receptor potential channel family, Orai family and stromal interaction molecule 1
      (STIM1) might also be involved in the regulation of store-operated calcium
      channels (SOCCs). An increase in cytosolic free Ca2+ concentration promoted by
      store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells
      (PASMCs) is a major trigger for pulmonary vasoconstriction and proliferation and
      migration of PASMCs. In this study, our data revealed the following: (1) in both
      rat distal pulmonary arteries and PASMCs, chronic hypoxia exposure upregulated
      the expression of Orai1 and Orai2, without affecting Orai3 and STIM1; (2) either
      heterozygous knockout of HIF-1alpha in mice or knockdown of HIF-1alpha in PASMCs
      abolished the hypoxic upregulation of Orai2, but not Orai1, suggesting the
      hypoxic upregulation of Orai2 depends on HIF-1alpha; and (3) using small
      interference RNA knockdown strategies, Orai1, 2, 3 and STIM1 were all shown to
      mediate SOCE in hypoxic PASMCs. Together, these results suggested that the
      components of SOCCs, including Orai1, 2, 3 and STIM1, may lead to novel
      therapeutic targets for the treatment of chronic hypoxia-induced pulmonary
      hypertension.

PMID- 29188079
TI  - Structure-based design of functionalized 2-substituted and 1,2-disubstituted
      benzimidazole derivatives and their in vitro antibacterial efficacy.
AB  - The aim of this present study was to synthesize 2-substituted and 1,2
      disubstituted benzimidazole derivatives to investigate their antibacterial
      diversity for possible future drug design. The structure-based design of
      precursors 2-(1H-benzimidazol-2-yl)aniline 1, 2-(3,5-dinitro phenyl)-1H
      benzimidazole 3 and 2-benzyl-1H-benzimidazole 5 were achieved by the condensation
      reaction of o-phenylenediamine with anthranilic acid, 3,5-dinitrophenylbenzoic
      acid, and phenylacetic acid, respectively. The precursors 1, 3 and 5, upon
      reaction with six different electrophile-releasing agents, furnished the
      corresponding 2-substituted benzimidazole, 2a-f and 1,2-disubstituted
      benzimidazole derivatives 4a-f and 6a-f, respectively. The structural identity of
      the targeted compounds was authenticated by elemental analytical data and
      spectral information from FT-IR, UV, 1H, and 13C NMR. The outcome of the findings
      from the in vitro screening unveiled 2-benzyl-1-(phenylsulfonyl)-1H-benzimidazole
      6b as the most active derivative with lowest MIC value of 15.63 ug/mL.

PMID- 29188080
TI  - Oxidation characteristics of porous-nickel prepared by powder metallurgy and cast
      nickel at 1273 K in air for total oxidation time of 100 h.
AB  - The oxidation behavior of two types of inhomogeneous nickel was investigated in
      air at 1273 K for a total oxidation time of 100 h. The two types were porous
      sintered-nickel and microstructurally inhomogeneous cast-nickel. The porous
      nickel samples were fabricated by compacting Ni powder followed by sintering in
      vacuum at 1473 K for 2 h. The oxidation kinetics of the samples was determined
      gravimetrically. The topography and the cross-section microstructure of each
      oxidized sample were observed using optical and scanning electron microscopy. X
      ray diffractometry and X-ray energy dispersive analysis were used to determine
      the nature of the formed oxide phases. The kinetic results revealed that the
      porous-nickel samples had higher trend for irreproducibility. The average
      oxidation rate for porous- and cast-nickel samples was initially rapid, and then
      decreased gradually to become linear. Linear rate constants were 5.5 * 10-8 g/cm2
      s and 3.4 * 10-8 g/cm2 s for the porous- and cast-nickel samples, respectively.
      Initially a single-porous non-adherent NiO layer was noticed on the porous- and
      cast-nickel samples. After a longer time of oxidation, a non-adherent duplex NiO
      scale was formed. The two layers of the duplex scales were different in color.
      NiO particles were observed in most of the pores of the porous-nickel samples.
      Finally, the linear oxidation kinetics and the formation of porous non-adherent
      duplex oxide scales on the inhomogeneous nickel substrates demonstrated that the
      addition of new layers of NiO occurred at the scale/metal interface due to the
      thermodynamically possible reaction between Ni and the molecular oxygen migrating
      inwardly.

PMID- 29188081
TI  - Plaque Characteristics in the Superficial Femoral Artery Correlate with Walking
      Impairment Questionnaire Scores in Peripheral Arterial Disease: The Walking and
      Leg Circulation Study (WALCS) III.
AB  - Purpose: We studied associations of magnetic resonance imaging (MRI)-measured
      plaque area and relative percent lumen reduction in the proximal superficial
      femoral artery with Walking Impairment Questionnaire (WIQ) scores and quality of
      life in people with lower extremity peripheral arterial disease (PAD). Methods:
      Four-hundred forty-two participants with PAD underwent cross-sectional imaging of
      the proximal superficial femoral artery with MRI, and completed the WIQ and the
      Short-Form-12 mental and physical functioning questionnaires. Questionnaires were
      scored on a 0-100 scale (100=best). Results adjust for age, sex, race, the ankle
      brachial index (ABI), comorbidities, and other covariates. Results: Adjusting for
      age, sex, race, ABI, comorbidities, and other covariates, higher mean plaque area
      was associated with poorer WIQ distance scores (1st quintile (least plaque)-44.8,
      2nd quintile-43.3, 3rd quintile-38.9, 4th quintile-34.6, 5th quintile (greatest
      plaque)-30.6, p trend <0.001) and poorer WIQ speed scores (1st quintile-40.6, 2nd
      quintile-39.6, 3rd quintile-39.5, 4th quintile-32.8, 5th quintile-33.0, p trend
      =0.019). Similar associations of higher maximum plaque area, mean lumen
      reduction, and maximum lumen reduction with poorer WIQ distance and speed scores
      were observed. Plaque measures were not associated with WIQ stair climbing scores
      or SF-12 scores. Conclusion: Among participants with PAD, greater plaque burden
      and smaller lumen area in the proximal superficial femoral artery are associated
      with poorer walking endurance and slower walking speed as measured by the WIQ,
      even after adjusting for the ABI.

PMID- 29188082
TI  - Microarray analyzer based on wide field fluorescent microscopy with laser
      illumination and a device for speckle suppression.
AB  - A microarray analyzer was developed to obtain images and measure the fluorescence
      intensity of microarrays at three wavelengths from 380 nm to 850 nm. The analyzer
      contains lasers to excite fluorescence, barrier filters, optics to project images
      on an image detector, and a device for suppressing laser speckles on the
      microarray support. The speckle suppression device contains a fibre-optic bundle
      and a rotating mirror positioned in a way to change the distance between the
      bundle butt and mirror surface during each mirror revolution. The analyzer
      provides for measurements with accuracy within +/- 5%. Obtaining images at
      several exposure times allowed a significant expansion in the range of measured
      fluorescence intensities. The analyzer is useful for high throughput analysis of
      the same type of microarrays.

PMID- 29188083
TI  - Increasing the field of view of adaptive optics scanning laser ophthalmoscopy.
AB  - An adaptive optics scanning laser ophthalmoscope (AO-SLO) set-up with two
      deformable mirrors (DM) is presented. It allows high resolution imaging of the
      retina on a 4 degrees *4 degrees  field of view (FoV), considering a 7 mm pupil
      diameter at the entrance of the eye. Imaging on such a FoV, which is larger
      compared to classical AO-SLO instruments, is allowed by the use of the two DMs.
      The first DM is located in a plane that is conjugated to the pupil of the eye and
      corrects for aberrations that are constant in the FoV. The second DM is
      conjugated to a plane that is located ~0.7 mm anterior to the retina. This DM
      corrects for anisoplanatism effects within the FoV. The control of the DMs is
      performed by combining the classical AO technique, using a Shack-Hartmann wave
      front sensor, and sensorless AO, which uses a criterion characterizing the image
      quality. The retinas of four healthy volunteers were imaged in-vivo with the
      developed instrument. In order to assess the performance of the set-up and to
      demonstrate the benefits of the 2 DM configuration, the acquired images were
      compared with images taken in conventional conditions, on a smaller FoV and with
      only one DM. Moreover, an image of a larger patch of the retina was obtained by
      stitching of 9 images acquired with a 4 degrees *4 degrees  FoV, resulting in a
      total FoV of 10 degrees *10 degrees . Finally, different retinal layers were
      imaged by shifting the focal plane.

PMID- 29188084
TI  - Lens internal curvature effects on age-related eye model and lens paradox.
AB  - The gradient index (GRIN) model is the most accurate way to represent the eye
      lens which, because of its growth mode, is a lamellar, shell-like structure. The
      GRIN is thought to provide optical properties that counteract age-related changes
      in curvature that would otherwise create an increasingly myopic eye: the so
      called lens paradox. This article investigates how fine-tuning the refractive
      index and the internal curvatures of the lenticular indicial contours may prevent
      the ageing eye from becoming myopic. A system matrix approach is applied for
      analysis of a shell model with 200 shells to obtain the paraxial characteristics
      of the eye model.

PMID- 29188085
TI  - Novel health monitoring method using an RGB camera.
AB  - In this paper we present a novel health monitoring method by estimating the heart
      rate and respiratory rate using an RGB camera. The heart rate and the respiratory
      rate are estimated from the photoplethysmography (PPG) and the respiratory
      motion. The method mainly operates by using the green spectrum of the RGB camera
      to generate a multivariate PPG signal to perform multivariate de-noising on the
      video signal to extract the resultant PPG signal. A periodicity based voting
      scheme (PVS) was used to measure the heart rate and respiratory rate from the
      estimated PPG signal. We evaluated our proposed method with a state of the art
      heart rate measuring method for two scenarios using the MAHNOB-HCI database and a
      self collected naturalistic environment database. The methods were furthermore
      evaluated for various scenarios at naturalistic environments such as a motion
      variance session and a skin tone variance session. Our proposed method operated
      robustly during the experiments and outperformed the state of the art heart rate
      measuring methods by compensating the effects of the naturalistic environment.

PMID- 29188086
TI  - In vivo study of optical speckle decorrelation time across depths in the mouse
      brain.
AB  - The strong optical scattering of biological tissue confounds our ability to focus
      light deeply into the brain beyond depths of a few hundred microns. This
      challenge can be potentially overcome by exploiting wavefront shaping techniques
      which allow light to be focused through or inside scattering media. However,
      these techniques require the scattering medium to be static, as changes in the
      arrangement of the scatterers between the wavefront recording and playback steps
      reduce the fidelity of the focus that is formed. Furthermore, as the thickness of
      the scattering medium increases, the influence of the dynamic nature becomes more
      severe due to the growing number of scattering events experienced by each photon.
      In this paper, by examining the scattering dynamics in the mouse brain in vivo
      via multispeckle diffusing wave spectroscopy (MSDWS) using a custom fiber probe
      that simulates a point-like source within the brain, we investigate the
      relationship between this decorrelation time and the depth of the point-like
      light source inside the living mouse brain at depths up to 3.2 mm.

PMID- 29188087
TI  - Elemental analysis of the thyroid by laser induced breakdown spectroscopy.
AB  - The thyroid is an important hormone regulation organ. Laser induced breakdown
      spectroscopy (LIBS) is developed to assess iodine and other essential elements in
      the thyroid (of rats). Subjects are administered 0.05% iodine water for 0, 6, and
      12 days before the thyroid is extracted. Pronounced iodine, sodium, calcium, and
      potassium emissions are observed at approximately 746, 589, 395/422, and 766/770
      nm, respectively. Iodine emission is surprisingly highest in 0 day subjects,
      lowest after 6 days, and recovers by 12 days. This follows the Wolff-Chaikoff
      effect as ingestion of excess iodine reduces thyroid iodine and iodine is
      essential for hormone production. LIBS is a promising method for trace elemental
      analysis of the thyroid.

PMID- 29188088
TI  - Virtually increased acceptance angle for efficient estimation of spatially
      resolved reflectance in the subdiffusive regime: a Monte Carlo study.
AB  - Light propagation in biological tissues is frequently modeled by the Monte Carlo
      (MC) method, which requires processing of many photon packets to obtain adequate
      quality of the observed backscattered signal. The computation times further
      increase for detection schemes with small acceptance angles and hence small
      fraction of the collected backscattered photon packets. In this paper, we
      investigate the use of a virtually increased acceptance angle for efficient MC
      simulation of spatially resolved reflectance and estimation of optical properties
      by an inverse model. We devise a robust criterion for approximation of the
      maximum virtual acceptance angle and evaluate the proposed methodology for a wide
      range of tissue-like optical properties and various source configurations.

PMID- 29188089
TI  - Improving lateral resolution and image quality of optical coherence tomography by
      the multi-frame superresolution technique for 3D tissue imaging.
AB  - The multi-frame superresolution technique is introduced to significantly improve
      the lateral resolution and image quality of spectral domain optical coherence
      tomography (SD-OCT). Using several sets of low resolution C-scan 3D images with
      lateral sub-spot-spacing shifts on different sets, the multi-frame
      superresolution processing of these sets at each depth layer reconstructs a
      higher resolution and quality lateral image. Layer by layer processing yields an
      overall high lateral resolution and quality 3D image. In theory, the
      superresolution processing including deconvolution can solve the diffraction
      limit, lateral scan density and background noise problems together. In
      experiment, the improved lateral resolution by ~3 times reaching 7.81 um and 2.19
      um using sample arm optics of 0.015 and 0.05 numerical aperture respectively as
      well as doubling the image quality has been confirmed by imaging a known
      resolution test target. Improved lateral resolution on in vitro skin C-scan
      images has been demonstrated. For in vivo 3D SD-OCT imaging of human skin,
      fingerprint and retina layer, we used the multi-modal volume registration method
      to effectively estimate the lateral image shifts among different C-scans due to
      random minor unintended live body motion. Further processing of these images
      generated high lateral resolution 3D images as well as high quality B-scan images
      of these in vivo tissues.

PMID- 29188090
TI  - Erratum: Optoacoustic response of gold nanorods in soft phantoms using high-power
      diode laser assemblies at 870 and 905 nm: erratum.
AB  - [This corrects the article on p. 1430 in vol. 8, PMID: 28663839.].

PMID- 29188091
TI  - Compact fs ytterbium fiber laser at 1010 nm for biomedical applications.
AB  - Ytterbium-doped fiber lasers (YDFLs) working in the near-infrared (NIR) spectral
      window and capable of high-power operation are popular in recent years. They have
      been broadly used in a variety of scientific and industrial research areas,
      including light bullet generation, optical frequency comb formation, materials
      fabrication, free-space laser communication, and biomedical diagnostics as well.
      The growing interest in YDFLs has also been cultivated for the generation of high
      power femtosecond (fs) pulses. Unfortunately, the operating wavelengths of fs
      YDFLs have mostly been confined to two spectral bands, i.e., 970-980 nm through
      the three-level energy transition and 1030-1100 nm through the quasi three-level
      energy transition, leading to a spectral gap (990-1020 nm) in between, which is
      attributed to an intrinsically weak gain in this wavelength range. Here we
      demonstrate a high-power mode-locked fs YDFL operating at 1010 nm, which is
      accomplished in a compact and cost-effective package. It exhibits superior
      performance in terms of both short-term and long-term stability, i.e., <0.3%
      (peak intensity over 2.4 MUs) and <4.0% (average power over 24 hours),
      respectively. To illustrate the practical applications, it is subsequently
      employed as a versatile fs laser for high-quality nonlinear imaging of biological
      samples, including two-photon excited fluorescence microscopy of mouse kidney and
      brain sections, as well as polarization-sensitive second-harmonic generation
      microscopy of potato starch granules and mouse tail muscle. It is anticipated
      that these efforts will largely extend the capability of fs YDFLs which is
      continuously tunable over 970-1100 nm wavelength range for wideband hyperspectral
      operations, serving as a promising complement to the gold-standard Ti:sapphire fs
      lasers.

PMID- 29188092
TI  - Real time complete Stokes polarimetric imager based on a linear polarizer array
      camera for tissue polarimetric imaging.
AB  - Tissue polarimetric imaging measures Mueller matrices of tissues or Stokes
      vectors of the emergent light from tissues (normally using incidence with a fixed
      polarization state) over a field of view, and has demonstrated utility in a
      number of surgical and diagnostic applications. Here we introduce a compact
      complete Stokes polarimetric imager that can work for multiple wavelength bands
      with a frame-rate suitable for real-time applications. The imager was validated
      with standard polarizing components, and then employed as a polarization state
      analyzer of a Mueller imaging polarimeter and a standalone Stokes imaging
      polarimeter respectively to image the process of dehydration of bovine tendon
      tissue. The results obtained in this work suggested that the polarization
      properties of the samples rich of collagen fibres can change with the degree of
      dehydration, and therefore, dehydration of the samples prepared for polarimetric
      imaging (e.g. polarimetric microscopy) should be carefully controlled.

PMID- 29188093
TI  - Fully automated laser ray tracing system to measure changes in the crystalline
      lens GRIN profile.
AB  - Measuring the lens gradient refractive index (GRIN) accurately and reliably has
      proven an extremely challenging technical problem. A fully automated laser ray
      tracing (LRT) system was built to address this issue. The LRT system captures
      images of multiple laser projections before and after traversing through an ex
      vivo lens. These LRT images, combined with accurate measurements of the lens
      geometry, are used to calculate the lens GRIN profile. Mathematically, this is an
      ill-conditioned problem; hence, it is essential to apply biologically relevant
      constraints to produce a feasible solution. The lens GRIN measurements were
      compared with previously published data. Our GRIN retrieval algorithm produces
      fast and accurate measurements of the lens GRIN profile. Experiments to study the
      optics of physiologically perturbed lenses are the future direction of this
      research.

PMID- 29188094
TI  - Molecular response of mitochondria to a short-duration femtosecond-laser
      stimulation.
AB  - The research of mitochondrial dysfunction is of great importance and implicated
      in a range of neurodegenerative diseases. Traditionally, to investigate
      mitochondrial dynamics and functions, mitochondria are usually stimulated
      indirectly by treating cells with exogenous chemicals like oxidative agents. Such
      treatment lacks precision and controllability, and will simultaneously activate
      unknown complex cell processes. In this study, we report that two-photon 100-MUs
      line scan by a femtosecond laser can induce restorable fragmentation or swelling
      of any targeted mitochondria instead of ablation or disruption. It can be defined
      by a customized two-photon line scan and inserted into any microscopy sequence as
      a single frame. The mitochondrial response is dependent on the peak power of
      laser pulses, cellular oxidative environment, and membrane permeability
      transition pores of mitochondria. The translocation of cytochrome C and Bax can
      be regulated by the photostimulation. Moreover, significant upregulation of Bcl-2
      can be observed if the whole cell is stimulated. Those results suggest the
      mitochondrial and molecular response to photostimulation is quite complex. This
      femtosecond-laser stimulation method can thus provide a very noninvasive,
      precise, and controllable method to stimulate single target mitochondria for
      related biological research.

PMID- 29188095
TI  - Comparison of four methods of surface roughness assessment of corneal stromal bed
      after lamellar cutting.
AB  - Corneal lamellar cutting with a blade or femtosecond laser (FSL) is commonly used
      during refractive surgery and corneal grafts. Surface roughness of the cutting
      plane influences postoperative visual acuity but is difficult to assess reliably.
      For the first time, we compared chromatic confocal microscopy (CCM) with scanning
      electron microscopy, atomic force microscopy (AFM) and focus-variation microscopy
      (FVM) to characterize surfaces of variable roughness after FSL cutting. The small
      area allowed by AFM hinders conclusive roughness analysis, especially with
      irregular cuts. FVM does not always differentiate between smooth and rough
      surfaces. Finally, CCM allows analysis of large surfaces and differentiates
      between surface states.

PMID- 29188096
TI  - Cerebral time domain-NIRS: reproducibility analysis, optical properties,
      hemoglobin species and tissue oxygen saturation in a cohort of adult subjects.
AB  - The reproducibility of cerebral time-domain near-infrared spectroscopy (TD-NIRS)
      has not been investigated so far. Besides, reference intervals of cerebral
      optical properties, of absolute concentrations of deoxygenated-hemoglobin (HbR),
      oxygenated-hemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation
      (StO2) and their variability have not been reported. We have addressed these
      issues on a sample of 88 adult healthy subjects. TD-NIRS measurements at 690,
      785, 830 nm were fitted with the diffusion model for semi-infinite homogenous
      media. Reproducibility, performed on 3 measurements at 5 minutes intervals,
      ranges from 1.8 to 6.9% for each of the hemoglobin species. The mean +/- SD
      global values of HbR, HbO, HbT, StO2 are respectively 24 +/- 7 MUM, 33.3 +/- 9.5
      MUM, 57.4 +/- 15.8 MUM, 58 +/- 4.2%. StO2 displays the narrowest range of
      variability across brain regions.

PMID- 29188098
TI  - Active thermodynamic contrast imaging for label-free tumor detection in a murine
      xenograft tumor model.
AB  - Passive thermal imaging provides a limited differentiation between a tumor and
      neighboring tissue based on the temperature difference. We propose active
      thermodynamic contrast imaging (ATCI) with convection thermal modulators to
      provide more physiologically relevant parameters with high contrast such as the
      rate of temperature change, and thermal recovery time for tumor detection with a
      murine xenograft tumor model. With early stage tumors, we found the average rate
      of temperature change was higher in the tumor (0.22 +/- 0.06 [Formula: see
      text]/sec) than that of neighboring tissue (0.13 +/- 0.01 [Formula: see
      text]/sec) with heating modulation. With established tumors (volume > 100 mm3),
      this tendency was greater. On the other hand, the thermal recovery time was
      shorter in tumor tissue (tau = 7.30 +/- 0.59 sec) than that of neighboring tissue
      (tau = 11.91 +/- 2.22 sec). We also found distinct thermal contrast with cooling
      modulation. These data suggest ATCI is a potential tumor detection modality for
      clinical application with its inherently label-free and physiology-based
      approach. Furthermore, this strategy may find applications in endoscopic tumor
      detection in the future.

PMID- 29188097
TI  - Noninvasive structural and microvascular anatomy of oral mucosae using handheld
      optical coherence tomography.
AB  - In this study, we demonstrated the feasibility of using a handheld optical
      coherence tomography (OCT) for in vivo visualizations of the microstructural and
      microvascular features of various oral mucosal types. To scan arbitrary locations
      of the oral mucosa, a scanning probe was developed, composed of a probe body
      fabricated by a 3D printer, miniaturized two-axis galvanometer, relay lenses, and
      reflective prism. With a 3D printing technique, the probe weight and the system
      volume were greatly reduced, enabling the effective improvement of imaging
      artifacts from unconscious motion and system complexity. Additionally, in our
      design, the distal end of the probe can be switched to fit various oral
      conditions, and the optical parameters of the probe, such as the transverse
      resolution, working distance, and probe length can be easily varied. The results
      showed that the epithelium and lamina propria layers, as well as the fungiform
      papilla and salivary gland, were differentiated. Moreover, various
      microcirculation features at different mucosal sites were identified that are
      potentially effective indicators for the diagnosis of premalignant lesions. The
      demonstrated results indicate that the developed OCT system is a promising tool
      for noninvasive imaging of oral mucosae.

PMID- 29188099
TI  - Serial optical coherence scanning reveals an association between cardiac function
      and the heart architecture in the aging rodent heart.
AB  - Normal aging is accompanied by structural changes in the heart architecture. To
      explore this remodeling, we used a serial optical coherence tomography scanner to
      image entire mouse hearts at micron scale resolution. Ex vivo hearts of 7 young
      (4 months) and 5 old (24 months) C57BL/6 mice were acquired with the imaging
      platform. OCT of the myocardium revealed myofiber orientation changing linearly
      from the endocardium to the epicardium. In old mice, this rate of change was
      lower when compared to young mice while the average volume of old mice hearts was
      significantly larger (p<0.05). Myocardial wall thickening was also accompanied by
      extracellular spacing in the endocardium, resulting in a lower OCT attenuation
      coefficient in old mice endocardium (p<0.05). Prior to serial sectioning, cardiac
      function of the same hearts was imaged in vivo using MRI and revealed a reduced
      ejection fraction with aging. The use of a serial optical coherence tomography
      scanner allows new insight into fine age-related changes of the heart associated
      with changes in heart function.

PMID- 29188100
TI  - Erratum: In vivo study of optical speckle decorrelation time across depths in the
      mouse brain: erratum.
AB  - [This corrects the article on p. 4855 in vol. 8.].

PMID- 29188101
TI  - Photodynamic opening of blood-brain barrier.
AB  - Photodynamic treatment (PDT) causes a significant increase in the permeability of
      the blood-brain barrier (BBB) in healthy mice. Using different doses of laser
      radiation (635 nm, 10-40 J/cm2) and photosensitizer (5-aminolevulinic acid - 5
      ALA, 20 and 80 mg/kg, i.v.), we found that the optimal PDT for the reversible
      opening of the BBB is 15 J/cm2 and 5-ALA, 20 mg/kg, exhibiting brain tissues
      recovery 3 days after PDT. Further increases in the laser radiation or 5-ALA
      doses have no amplifying effect on the BBB permeability, but are associated with
      severe damage of brain tissues. These results can be an informative platform for
      further studies of new strategies in brain drug delivery and for better
      understanding of mechanisms underlying cerebrovascular effects of PDT-related
      fluorescence guided resection of brain tumor.

PMID- 29188102
TI  - Automated drusen detection in dry age-related macular degeneration by multiple
      depth, en face optical coherence tomography.
AB  - We introduce a method to automatically detect drusen in dry age-related macular
      degeneration (AMD) from optical coherence tomography with minimum need for layer
      segmentation. The method is based on the en face detection of drusen areas in C
      scans at certain distances above the Bruch's membrane, circumventing the
      difficult task of pathologic retinal pigment epithelium segmentation. All types
      of drusen can be detected, including the challenging subretinal drusenoid
      deposits (pseudodrusen). The high sensitivity and accuracy demonstrated here
      shows its potential for detection of drusen onset in early AMD.

PMID- 29188103
TI  - Comparison of second harmonic microscopy images of collagen-based ocular tissues
      with 800 and 1045 nm.
AB  - Second harmonic generation (SHG) imaging is a well-suited multiphoton technique
      allowing visualization of biological tissues mainly composed of collagen with
      submicron resolution. Despite its inherent confocal properties, imaging of deeper
      layers within thick samples has still some limitations. Although the use of
      longer wavelengths might help to overcome this, the dependence between SHG
      signals and wavelength is still under discussion. We report here on the
      dependence with wavelength of SHG signals from collagen-based ocular tissues. The
      quality of SHG images for two commonly used excitation wavelengths (800 and 1045
      nm) is studied. The analysis of the collagen structural information reveals that
      the information provided by both wavelengths is similar. It was also found that,
      independently of the depth location, 1045-nm SHG images presented always lower
      signal levels than those acquired with 800 nm. However, the contrast of the
      former images was higher, what may improve the visualization of certain features
      of interest.

PMID- 29188104
TI  - Open-source do-it-yourself multi-color fluorescence smartphone microscopy.
AB  - Fluorescence microscopy is an important technique for cellular and
      microbiological investigations. Translating this technique onto a smartphone can
      enable particularly powerful applications such as on-site analysis, on-demand
      monitoring, and point-of-care diagnostics. Current fluorescence smartphone
      microscope setups require precise illumination and imaging alignment which
      altogether limit its broad adoption. We report a multi-color fluorescence
      smartphone microscope with a single contact lens-like add-on lens and slide
      launched total-internal-reflection guided illumination for three common tasks in
      investigative fluorescence microscopy: autofluorescence, fluorescent stains, and
      immunofluorescence. The open-source, simple and cost-effective design has the
      potential for do-it-yourself fluorescence smartphone microscopy.

PMID- 29188105
TI  - Adaptive optics stochastic optical reconstruction microscopy (AO-STORM) by
      particle swarm optimization.
AB  - Stochastic optical reconstruction microscopy (STORM) can achieve resolutions of
      better than 20nm imaging single fluorescently labeled cells. However, when
      optical aberrations induced by larger biological samples degrade the point spread
      function (PSF), the localization accuracy and number of localizations are both
      reduced, destroying the resolution of STORM. Adaptive optics (AO) can be used to
      correct the wavefront, restoring the high resolution of STORM. A challenge for AO
      STORM microscopy is the development of robust optimization algorithms which can
      efficiently correct the wavefront from stochastic raw STORM images. Here we
      present the implementation of a particle swarm optimization (PSO) approach with a
      Fourier metric for real-time correction of wavefront aberrations during STORM
      acquisition. We apply our approach to imaging boutons 100 MUm deep inside the
      central nervous system (CNS) of Drosophila melanogaster larvae achieving a
      resolution of 146 nm.

PMID- 29188106
TI  - Non-invasive assessment of human cone photoreceptor function.
AB  - Vision begins when light isomerizes the photopigments within photoreceptors.
      Noninvasive cellular-scale observation of the structure of the human
      photoreceptor mosaic is made possible through the use of adaptive optics (AO)
      enhanced ophthalmoscopes, but establishing noninvasive objective measures of
      photoreceptor function on a similar scale has been more difficult. AO
      ophthalmoscope images acquired with near-infrared light show that individual cone
      photoreceptor reflectance can change in response to a visible stimulus. Here we
      show that the intrinsic response depends on stimulus wavelength and intensity,
      and that its action spectrum is well-matched to the spectral sensitivity of cone
      mediated vision. Our results demonstrate that the cone reflectance response is
      mediated by photoisomerization, thus making it a direct measure of photoreceptor
      function.

PMID- 29188107
TI  - Real-time endoscopic optical properties imaging.
AB  - With almost 50% of all surgeries in the U.S. being performed as minimally
      invasive procedures, there is a need to develop quantitative endoscopic imaging
      techniques to aid surgical guidance. Recent developments in widefield optical
      imaging make endoscopic implementations of real-time measurement possible. In
      this work, we introduce a proof-of-concept endoscopic implementation of a
      functional widefield imaging technique called 3D single snapshot of optical
      properties (3D-SSOP) that provides quantitative maps of absorption and reduced
      scattering optical properties as well as surface topography with simple
      instrumentation added to a commercial endoscope. The system's precision and
      accuracy is validated using tissue-mimicking phantoms, showing a max error of
      0.004 mm-1, 0.05 mm-1, and 1.1 mm for absorption, reduced scattering, and sample
      topography, respectively. This study further demonstrates video acquisition of a
      moving phantom and an in vivo sample with a framerate of approximately 11 frames
      per second.

PMID- 29188108
TI  - Ultrahigh-resolution optical coherence elastography through a micro-endoscope:
      towards in vivo imaging of cellular-scale mechanics.
AB  - In this paper, we describe a technique capable of visualizing mechanical
      properties at the cellular scale deep in living tissue, by incorporating a
      gradient-index (GRIN)-lens micro-endoscope into an ultrahigh-resolution optical
      coherence elastography system. The optical system, after the endoscope, has a
      lateral resolution of 1.6 um and an axial resolution of 2.2 um. Bessel beam
      illumination and Gaussian mode detection are used to provide an extended depth-of
      field of 80 um, which is a 4-fold improvement over a fully Gaussian beam case
      with the same lateral resolution. Using this system, we demonstrate quantitative
      elasticity imaging of a soft silicone phantom containing a stiff inclusion and a
      freshly excised malignant murine pancreatic tumor. We also demonstrate
      qualitative strain imaging below the tissue surface on in situ murine muscle. The
      approach we introduce here can provide high-quality extended-focus images through
      a micro-endoscope with potential to measure cellular-scale mechanics deep in
      tissue. We believe this tool is promising for studying biological processes and
      disease progression in vivo.

PMID- 29188109
TI  - Speckle variance OCT for depth resolved assessment of the viability of bovine
      embryos.
AB  - The morphology of embryos produced by in vitro fertilization (IVF) is commonly
      used to estimate their viability. However, imaging by standard microscopy is
      subjective and unable to assess the embryo on a cellular scale after compaction.
      Optical coherence tomography is an imaging technique that can produce a depth
      resolved profile of a sample and can be coupled with speckle variance (SV) to
      detect motion on a micron scale. In this study, day 7 post-IVF bovine embryos
      were observed either short-term (10 minutes) or long-term (over 18 hours) and
      analyzed by swept source OCT and SV to resolve their depth profile and
      characterize micron-scale movements potentially associated with viability. The
      percentage of en face images showing movement at any given time was calculated as
      a method to detect the vital status of the embryo. This method could be used to
      measure the levels of damage sustained by an embryo, for example after
      cryopreservation, in a rapid and non-invasive way.

PMID- 29188110
TI  - Optimal hemoglobin extinction coefficient data set for near-infrared
      spectroscopy.
AB  - Extinction coefficient (epsilon) is a critical parameter for quantification of
      oxy-, deoxy-, and total-hemoglobin concentrations (Delta[HbO2], Delta[Hb],
      Delta[tHb]) from optical measurements of Near-infrared spectroscopy (NIRS). There
      are several different epsilon data sets which were frequently used in NIRS
      quantification. A previous study reported that even a small variation in epsilon
      could cause a significant difference in hemodynamic measurements. Apparently the
      selection of an optimal epsilon data set is important for NIRS. We conducted
      oxygen-state-varied and blood-concentration-varied model experiments with 57
      human blood samples to mimic tissue hemodynamic variations. Seven reported
      epsilon data sets were evaluated by comparisons between quantifications and
      assumed values. We found that the Moaveni et al (1970)' epsilon data set was the
      optimal one, the NIRS quantification varied significantly among different epsilon
      data sets and parameter Delta[tHb] was most sensitive to epsilon data sets
      selection.

PMID- 29188111
TI  - Automatic detection of the foveal center in optical coherence tomography.
AB  - We propose a method for automatic detection of the foveal center in optical
      coherence tomography (OCT). The method is based on a pixel-wise classification of
      all pixels in an OCT volume using a fully convolutional neural network (CNN) with
      dilated convolution filters. The CNN-architecture contains anisotropic dilated
      filters and a shortcut connection and has been trained using a dynamic training
      procedure where the network identifies its own relevant training samples. The
      performance of the proposed method is evaluated on a data set of 400 OCT scans of
      patients affected by age-related macular degeneration (AMD) at different severity
      levels. For 391 scans (97.75%) the method identified the foveal center with a
      distance to a human reference less than 750 MUm, with a mean (+/- SD) distance of
      71 MUm +/- 107 MUm. Two independent observers also annotated the foveal center,
      with a mean distance to the reference of 57 MUm +/- 84 MUm and 56 MUm +/- 80 MUm,
      respectively. Furthermore, we evaluate variations to the proposed network
      architecture and training procedure, providing insight in the characteristics
      that led to the demonstrated performance of the proposed method.

PMID- 29188112
TI  - Multimode fibre based imaging for optically cleared samples.
AB  - Optical clearing is emerging as a popular approach particularly for studies in
      neuroscience. However the use of corrosive clearing solutions typically requires
      sophisticated objectives or extreme care with optical components chosen for
      single- or multi-photon imaging. In contrast to the use of complex, custom-made
      microscope objectives, we show that the use of a corrected multimode fibre (MMF)
      offers a route that is resistant to corrosion, can be used in clearing media, is
      not constrained by the refractive index of the immersion medium and offers
      flexible working distances. Using a corrected MMF, we demonstrate fluorescence
      imaging of beads and stained neuroblastoma cells through optically cleared mouse
      brain tissue, as well as imaging in an extreme oxidative environment to show the
      versatility of our approach. Additionally, we perform Raman imaging of
      polystyrene beads in clearing media to demonstrate that this approach may be used
      for vibrational spectroscopy of optically cleared samples.

PMID- 29188113
TI  - Label-free fiber optic optrode for the detection of class C beta-lactamases
      expressed by drug resistant bacteria.
AB  - This paper reports the experimental assessment of an automated optical assay
      based on label free optical fiber optrodes for the fast detection of class C beta
      lactamases (AmpC BLs), actually considered as one of the most important sources
      of resistance to beta-lactams antibiotics expressed by resistant bacteria.
      Reflection-type long period fiber gratings (RT-LPG) have been used as highly
      sensitive label free optrodes, while a higher affine boronic acid-based ligand
      was here selected to enhance the overall assay performances compared to those
      obtained in our first demonstration. In order to prove the feasibility analysis
      towards a fully automated optical assay, an engineered system was developed to
      simultaneously manipulate and interrogate multiple fiber optic optrodes in the
      different phases of the assay. The automated system tested in AmpC solutions at
      increasing concentrations demonstrated a limit of detection (LOD) of 6 nM, three
      times better when compared with the results obtained in our previous work.
      Moreover, the real effectiveness of the proposed optical assay has been also
      confirmed in complex matrices as the case of lysates of Escherichia coli
      overexpressing AmpC.

PMID- 29188114
TI  - Optical surface plasmon resonance sensor modified by mutant glucose/galactose
      binding protein for affinity detection of glucose molecules.
AB  - Transdermal extraction of interstitial fluid (ISF) offers an attractive method
      for minimally invasive blood glucose monitoring. However, only a minute volume of
      ISF could be transdermally extracted, which is required to be diluted to form a
      manipulable volume of fluid for easy collection, transportation, and glucose
      detection. Therefore, a high-resolution glucose detection method is required for
      detecting glucose concentration in diluted ISF. In this paper, an optical surface
      plasmon resonance (SPR) sensor modified by the glucose/galactose-binding (GGB)
      protein which has good affinity to glucose molecules was presented for specific
      and sensitive glucose detection. The GGB protein was mutated at different sites
      for thiol coupling with the SPR surface and adjusting the affinity between
      glucose molecules and GGB protein. And the immobilization process of the GGB
      protein onto the surface of SPR sensor was optimized. Then, the stability of the
      SPR sensor modified with GGB protein was tested immediately and two weeks after
      immobilization. The coefficient of variation for glucose concentration
      measurement was less than 4.5%. By further mutation of the GGB protein at the
      A213S and L238S sites, the measurement range of the SPR sensor was adjusted to
      0.1-100 mg/dL, which matches the glucose concentration range of 5-10 times
      diluted ISF (3-100 mg/dL). These results suggest that the SPR biosensor
      immobilized with GGB protein has the potential for continuous glucose monitoring
      by integrating into the microfluidic ISF extraction chip.

PMID- 29188115
TI  - Raman spectral post-processing for oral tissue discrimination - a step for an
      automatized diagnostic system.
AB  - Most oral injuries are diagnosed by histopathological analysis of a biopsy, which
      is an invasive procedure and does not give immediate results. On the other hand,
      Raman spectroscopy is a real time and minimally invasive analytical tool with
      potential for the diagnosis of diseases. The potential for diagnostics can be
      improved by data post-processing. Hence, this study aims to evaluate the
      performance of preprocessing steps and multivariate analysis methods for the
      classification of normal tissues and pathological oral lesion spectra. A total of
      80 spectra acquired from normal and abnormal tissues using optical fiber Raman
      based spectroscopy (OFRS) were subjected to PCA preprocessing in the z-scored
      data set, and the KNN (K-nearest neighbors), J48 (unpruned C4.5 decision tree),
      RBF (radial basis function), RF (random forest), and MLP (multilayer perceptron)
      classifiers at WEKA software (Waikato environment for knowledge analysis), after
      area normalization or maximum intensity normalization. Our results suggest the
      best classification was achieved by using maximum intensity normalization
      followed by MLP. Based on these results, software for automated analysis can be
      generated and validated using larger data sets. This would aid quick
      comprehension of spectroscopic data and easy diagnosis by medical practitioners
      in clinical settings.

PMID- 29188117
TI  - Efficiency enhancement of Raman spectroscopy at long working distance by
      parabolic reflector.
AB  - Raman spectroscopy is well suited for readily revealing information about bio
      samples. As such, this technique has been applied to a wide range of areas,
      particularly in bio-medical diagnostics. Raman scattering in bio-samples
      typically has a low signal level due to the nature of inelastic scattering of
      photons. To achieve a high signal level, usually a high numerical aperture
      objective is employed. One drawback with these objectives is that their working
      distance is very short. However, in many cases of clinical diagnostics, a long
      working distance is preferable. We propose a practical solution to this problem
      by enhancing the Raman signal using a parabolic reflector. The high signal level
      is achieved through the large light collection solid angle of the parabolic
      reflector while the long working distance is ensured by the novel design of our
      microscope. The enhancement capability of the microscope was demonstrated on four
      types of samples. Among these samples, we find that this microscope design is
      most suitable for turbid samples.

PMID- 29188116
TI  - Multimodal nonlinear optical imaging of unstained retinas in the epi-direction
      with a sub-40 fs Yb-fiber laser.
AB  - Ultrafast lasers have potential use in ophthalmology for diagnoses through non
      invasive imaging as well as for surgical therapies or for evaluating
      pharmacological therapies. New ultrafast laser sources, operating at 1.07 MUm and
      sub-40 fs pulse durations, offer exciting possibilities in multiphoton imagining
      of the retina as the bulk of the eye is relatively transparent to this
      wavelength, three-photon excitation is not absorbed by DNA, and this wavelength
      has a greater penetration depth compared to the commonly used 800 nm Ti:Sapphire
      laser. In this work, we present the first epi-direction detected cross-section
      and depth-resolved images of unstained isolated retinas obtained using
      multiphoton microscopy with an ultrafast fiber laser centered at 1.07 MUm and a
      ~38 fs pulse duration. Spectral and temporal characterization of the
      autofluorescence signals show two distinct regions; the first one from the nerve
      fiber layer to the inner receptor layer, and the second being the retinal
      pigmented epithelium and choroid.

PMID- 29188118
TI  - Common-path phase-sensitive optical coherence tomography provides enhanced phase
      stability and detection sensitivity for dynamic elastography.
AB  - Phase-sensitive optical coherence elastography (PhS-OCE) is an emerging optical
      technique to quantify soft-tissue biomechanical properties. We implemented a
      common-path OCT design to enhance displacement sensitivity and optical phase
      stability for dynamic elastography imaging. The background phase stability was
      greater in common-path PhS-OCE (0.24 +/- 0.07nm) than conventional PhS-OCE (1.60
      +/- 0.11MUm). The coefficient of variation for surface displacement measurements
      using conventional PhS-OCE averaged 11% versus 2% for common-path PhS-OCE.
      Young's modulus estimates showed good precision (95% CIs) for tissue phantoms:
      24.96 +/- 2.18kPa (1% agar), 49.69 +/- 4.87kPa (1.5% agar), and 116.08 +/-
      12.14kPa (2% agar), respectively. Common-path PhS-OCE effectively reduced the
      amplitude of background dynamic optical phase instability to a sub-nanometer
      level, which provided a larger dynamic detection range and higher detection
      sensitivity for surface displacement measurements than conventional PhS-OCE.

PMID- 29188119
TI  - Multi-shaping technique reduces sidelobe magnitude in optical coherence
      tomography.
AB  - Shaping methods that are commonly used in Fourier-domain optical coherence
      tomography (FD-OCT) can suppress sidelobe artifacts in the axial direction, but
      they typically broaden the mainlobe of the point spread function (PSF) and reduce
      the axial resolution. To improve OCT image quality without this tradeoff, we have
      developed a multi-shaping technique that reduces the axial sidelobe magnitude
      dramatically and achieves better axial resolution than conventional shaping
      methods. This technique is robust and compatible in various FD-OCT imaging
      systems. Testing of multi-shaping in three experimental settings shows that it
      reduced the axial sidelobe contribution by more than 8 dB and improved the
      contrast to noise by at least 30% and up to three-fold. Multi-shaping enables
      accurate image analysis and is potentially useful in many OCT applications.

PMID- 29188120
TI  - Data-driven imaging of tissue inflammation using RGB-based hyperspectral
      reconstruction toward personal monitoring of dermatologic health.
AB  - Sensitive and accurate assessment of dermatologic inflammatory hyperemia in
      otherwise grossly normal-appearing skin conditions is beneficial to laypeople for
      monitoring their own skin health on a regular basis, to patients for looking for
      timely clinical examination, and to primary care physicians or dermatologists for
      delivering effective treatments. We propose that mathematical hyperspectral
      reconstruction from RGB images in a simple imaging setup can provide reliable
      visualization of hemoglobin content in a large skin area. Without relying on a
      complicated, expensive, and slow hyperspectral imaging system, we demonstrate the
      feasibility of determining heterogeneous or multifocal areas of inflammatory
      hyperemia associated with experimental photocarcinogenesis in mice. We envision
      that RGB-based reconstructed hyperspectral imaging of subclinical inflammatory
      hyperemic foci could potentially be integrated with the built-in camera (RGB
      sensor) of a smartphone to develop a simple imaging device that could offer
      affordable monitoring of dermatologic health.

PMID- 29188121
TI  - Statistical independence in nonlinear model-based inversion for quantitative
      photoacoustic tomography.
AB  - The statistical independence between the distributions of different chromophores
      in tissue has previously been used for linear unmixing with independent component
      analysis (ICA). In this study, we propose exploiting this statistical property in
      a nonlinear model-based inversion method. The aim is to reduce the sensitivity of
      the inversion scheme to errors in the modelling of the fluence, and hence provide
      more accurate quantification of the concentration of independent chromophores. A
      gradient-based optimisation algorithm is used to minimise the error functional,
      which includes a term representing the mutual information between the
      chromophores in addition to the standard least-squares data error. Both numerical
      simulations and an experimental phantom study are conducted to demonstrate that,
      in the presence of experimental errors in the fluence model, the proposed
      inversion method results in more accurate estimation of the concentrations of
      independent chromophores compared to the standard model-based inversion.

PMID- 29188122
TI  - Time domain diffuse correlation spectroscopy with a high coherence pulsed source:
      in vivo and phantom results.
AB  - Diffuse correlation spectroscopy (DCS), combined with time-resolved reflectance
      spectroscopy (TRS) or frequency domain spectroscopy, aims at path length (i.e.
      depth) resolved, non-invasive and simultaneous assessment of tissue composition
      and blood flow. However, while TRS provides a path length resolved data, the
      standard DCS does not. Recently, a time domain DCS experiment showed path length
      resolved measurements for improved quantification with respect to classical DCS,
      but was limited to phantoms and small animal studies. Here, we demonstrate time
      domain DCS for in vivo studies on the adult forehead and the arm. We achieve path
      length resolved DCS by means of an actively mode-locked Ti:Sapphire laser that
      allows high coherence pulses, thus enabling adequate signal-to-noise ratio in
      relatively fast (~1 s) temporal resolution. This work paves the way to the
      translation of this approach to practical in vivo use.

PMID- 29188124
TI  - Measuring blood oxygen saturation along a capillary vessel in human.
AB  - Measuring oxygen saturation in capillary vessels could provide valuable
      information on oxygen transport and tissue viability. Most spectroscopic
      measurement techniques, however, lack the spatial resolution to account for the
      small vessel dimensions within a scattering tissue and the steep gradients of
      oxygen saturation levels. Here, we developed a noninvasive technique for image
      guided confocal measurement of the optical absorption spectrum from a small
      region that is comparable in size to the cross section of a single capillary
      vessel. A wide range of oxygen saturation levels were measured in a single
      capillary in a human volunteer, with blood deoxygenation rates of 7.1% per
      hundred microns. The technique could help in studying oxygen exchange dynamics in
      tissues and could play a key role in future clinical diagnosis and therapeutic
      applications that require localized functional tissue inspection.

PMID- 29188125
TI  - Direct inversion algorithm for focal plane scanning optical projection
      tomography.
AB  - To achieve approximately parallel projection geometry, traditional optical
      projection tomography (OPT) requires the use of low numerical aperture (NA)
      objectives, which have a long depth-of-field at the expense of poor lateral
      resolution. Particularly promising methods to improve spatial resolution include
      ad-hoc post-processing filters that limit the effect of the system's MTF and
      focal-plane-scanning OPT (FPS-OPT), an alternative acquisition procedure that
      allows the use of higher NA objectives by limiting the effect of their shallow
      depth of field yet still assumes parallel projection rays during reconstruction.
      Here, we provide a detailed derivation that establishes the existence of a direct
      inversion formula for FPS-OPT. Based on this formula, we propose a point spread
      function-aware algorithm that is similar in form and complexity to traditional
      filtered backprojection (FBP). With simulations, we demonstrate that our point
      spread-function aware FBP for FPS-OPT leads to more accurate images than both
      traditional OPT with deconvolution and FPS-OPT with naive FBP reconstruction. We
      further illustrate the technique on experimental zebrafish data, which shows that
      our approach reduces out-of-focus blur compared to a direct FBP reconstruction
      with FPS-OPT.

PMID- 29188123
TI  - Dynamics of the human brain network revealed by time-frequency effective
      connectivity in fNIRS.
AB  - Functional near infrared spectroscopy (fNIRS) is a promising neuroimaging method
      for investigating networks of cortical regions over time. We propose a directed
      effective connectivity method (TPDC) allowing the capture of both time and
      frequency evolution of the brain's networks using fNIRS data acquired from
      healthy subjects performing a continuous finger-tapping task. Using this method
      we show the directed connectivity patterns among cortical motor regions involved
      in the task and their significant variations in the strength of information flow
      exchanges. Intra and inter-hemispheric connections during the motor task with
      their temporal evolution are also provided. Characterisation of the fluctuations
      in brain connectivity opens up a new way to assess the organisation of the brain
      to adapt to changing task constraints, or under pathological conditions.

PMID- 29188126
TI  - The United Nations Material Assistance to Survivors of Cholera in Haiti:
      Consulting Survivors and Rebuilding Trust.
AB  - Introduction: In August 2016, the United Nations (U.N.) Secretary General
      acknowledged the U.N.'s role in the cholera epidemic that has beset Haiti since
      2010. Two months later, the Secretary General issued a historic apology to the
      Haitian people before the U.N. General Assembly, for the organization's
      insufficient response to the cholera outbreak. These steps are part of the U.N.'s
      "new approach" to cholera in Haiti, which also includes launching a material
      assistance package for those most affected by cholera. Methods: This paper draws
      on the authors' experience and findings from consultations with more than 60,000
      victims and communities affected by disasters and violence in a dozen countries.
      We reviewed the literature on best practices for consultation with and outreach
      to communities affected by development and transitional justice programming, and
      reviewed our own findings from previous studies with a view to identifying
      recommendations for ensuring that the assistance package reflects the views of
      people affected by cholera. Results: The assistance package program is an
      opportunity to rebuild the relationship between the victims and the United
      Nations. This can only be achieved if victims are informed and engaged in the
      process. This consultation effort is also an opportunity to answer a set of key
      questions related to the nature, structure, and implementation of the victims'
      assistance program, but also how the program may be designed to contribute to
      rebuilding Haitians' confidence in the U.N. as an institution that promotes
      peace, human rights, and development. Discussion: We recommend that the
      consultations must be accompanied by an outreach effort that provides clear,
      accurate information on the assistance program, so that it begins to establish a
      dialogue between the U.N. and cholera victims. Finally, we conclude by offering a
      number of concrete next steps that the U.N. can take to kick start the
      consultation process.

PMID- 29188127
TI  - Enhancing Ebola Virus Disease Surveillance and Prevention in Counties Without
      Confirmed Cases in Rural Liberia: Experiences from Sinoe County During the Flare
      up in Monrovia, April to June, 2016.
AB  - Introduction: During the flare-ups of Ebola virus disease (EVD) in Liberia, Sinoe
      County reactivated the multi-sectorial EVD control strategy in order to be ready
      to respond to the eventual reintroduction of cases. This paper describes the
      impacts of the interventions implemented in Sinoe County during the last flare-up
      in Monrovia, from April 1 to June 9, 2016, using the resources provided during
      the original outbreak that ended a year ago. Methods: We conducted a descriptive
      study to describe the key interventions implemented in Sinoe County, the capacity
      available, the implications for the reactivation of the multi-sectoral EVD
      control strategy, and the results of the same. We also conducted a cross
      sectional study to analyze the impact of the interventions on the surveillance
      and on infection prevention and control (IPC). Results: The attrition of the
      staff trained during the original outbreak was low, and most of the supplies,
      equipment, and infrastructure from the original outbreak remained available. With
      an additional USD 1755, improvements were observed in the IPC indicators of
      triage, which increased from a mean of 60% at the first assessment to 77%
      (P=0.002). Additionally, personnel/staff training improved from 78% to 89%
      (P=0.04). The percentage of EVD death alerts per expected deaths investigated
      increased from 26% to 63% (P<0.0001). Discussion: The low attrition of the
      trained staff and the availability of most supplies, equipment, and
      infrastructure made the reactivation of the multi-sectoral EVD control strategy
      fast and affordable. The improvement of the EVD surveillance was possibly
      affected by the community engagement activities, awareness and mentoring of the
      health workers, and improved availability of clinicians in the facilities during
      the flare-up. The community engagement may contribute to the report of community
      based events, specifically community deaths. The mentoring of the staff during
      the supportive supervisions also contributed to improve the IPC indicators.

PMID- 29188129
TI  - A Rights-based Approach to Information in Humanitarian Assistance.
AB  - Crisis-affected populations and humanitarian aid providers are both becoming
      increasingly reliant on information and communications technology (ICTs) for
      finding and provisioning aid. This is exposing critical, unaddressed gaps in the
      legal and ethical frameworks that traditionally defined and governed the
      professional conduct of humanitarian action. The most acute of these gaps is a
      lack of clarity about what human rights people have regarding information in
      disaster, and the corresponding obligations incumbent upon governments and aid
      providers.  This need is lent urgency by emerging evidence demonstrating that the
      use of these technologies in crisis response may be, in some cases, causing harm
      to the very populations they intend to serve.  Preventing and mitigating these
      harms, while also working to responsibly ensure access to the benefits of
      information during crises, requires a rights-based framework to guide
      humanitarian operations. In this brief report, we provide a commentary that
      accompanies our report, the Signal Code: A Human Rights Approach to Information
      During Crisis, where we have identified five rights pertaining to the use of
      information and data during crisis which are grounded in current international
      human rights and customary law. It is our belief that the continued relevance of
      the humanitarian project, as it grows increasingly dependent on the use of data
      and ICTs, urgently requires a discussion of these rights and corresponding
      obligations.

PMID- 29188128
TI  - Influenza A Virus Infection Damages Zebrafish Skeletal Muscle and Exacerbates
      Disease in Zebrafish Modeling Duchenne Muscular Dystrophy.
AB  - INTRODUCTION: Both genetic and infectious diseases can result in skeletal muscle
      degeneration, inflammation, pain, and/or weakness. Duchenne muscular dystrophy
      (DMD) is the most common congenital muscle disease. DMD causes progressive muscle
      wasting due to mutations in Dystrophin. Influenza A and B viruses are frequently
      associated with muscle complications, especially in children. Infections activate
      an immune response and immunosuppressant drugs reduce DMD symptoms. These data
      suggest that the immune system may contribute to muscle pathology. However, roles
      of the immune response in DMD and Influenza muscle complications are not well
      understood. Zebrafish with dmd mutations are a well-characterized model in which
      to study the molecular and cellular mechanisms of DMD pathology. We recently
      showed that zebrafish can be infected by human Influenza A virus (IAV). Thus, the
      zebrafish is a powerful system with which to ask questions about the etiology and
      mechanisms of muscle damage due to genetic and/or infectious diseases. METHODS:
      We infected zebrafish with IAV and assayed muscle tissue structure, sarcolemma
      integrity, cell-extracellular matrix (ECM) attachment, and molecular and cellular
      markers of inflammation in response to IAV infection alone or in the context of
      DMD. RESULTS: We find that IAV-infected zebrafish display mild muscle
      degeneration with sarcolemma damage and compromised ECM adhesion. An innate
      immune response is elicited in muscle in IAV-infected zebrafish: NFkB signaling
      is activated, pro-inflammatory cytokine expression is upregulated, and
      neutrophils localize to sites of muscle damage. IAV-infected dmd mutants display
      more severe muscle damage than would be expected from an additive effect of dmd
      mutation and IAV infection, suggesting that muscle damage caused by Dystrophin
      deficiency and IAV infection is synergistic. DISCUSSION: These data demonstrate
      the importance of preventing IAV infections in individuals with genetic muscle
      diseases. Elucidating the mechanisms of immune-mediated muscle damage will not
      only apply to DMD and IAV, but also to other conditions where the immune system,
      inflammation, and muscle tissue are known to be affected, such as autoimmune
      diseases, cancer, and aging.

PMID- 29188130
TI  - First Wave of the 2016-17 Cholera Outbreak in Hodeidah City, Yemen - ACF
      Experience and Lessons Learned.
AB  - Introduction: Although cases were reported only in 2010 and 2011, cholera is
      probably endemic in Yemen. In the context of a civil war, a cholera outbreak was
      declared in different parts of the country October 6th, 2016. This paper
      describes the ACF outbreak response in Hodeidah city from October 28th, 2016 to
      February 28th, 2017 in order to add knowledge to this large outbreak. Methods:
      The ACF outbreak response in Hodeidah city included a case management component
      and prevention measures in the community. In partnership with the Ministry of
      Public Health and Population of Yemen (MoPHP), the case management component
      included a Cholera Treatment Center (CTC) implemented in the Al Thoraw hospital,
      11 Oral Rehydration Therapy Corners (ORTCs) and an active case finding system. In
      partnership with other stakeholders, prevention measures in the community,
      including access to safe water and hygiene promotion, were implemented in the
      most affected communities of the city. Results: From October 28th, 2016 until
      February 28th, 2017, ACF provided care to 8,270 Acute Watery Diarrhea (AWD)
      cases, of which 5,210 (63%) were suspected cholera cases, in the CTC and the 11
      ORTCs implemented in Hodeidah city. The attack rate was higher among people
      living in Al Hali district, with a peak in November 2016. At the CTC, 8% of
      children under 5 years-old also presented with Severe Acute Malnutrition (SAM).
      The Case-Fatality Rate (CFR) was low (0.07%) but 15% of admitted cases defaulted
      for cultural and security reasons. Environmental management lacked the
      information to appropriately target affected areas. Financial resources did not
      allow complete coverage of the city. Conclusion: Response to the first wave of a
      large cholera outbreak in Hodeidah city was successful in maintaining a CFR <1%
      in the CTC. However, considering the actual context of Yemen and its water
      infrastructure, much more efforts are needed to control the current outbreak
      resurgence.

PMID- 29188131
TI  - An Outbreak of Pseudomonas Aeruginosa Infection Linked to a "Black Friday"
      Piercing Event.
AB  - Introduction: Outbreaks linked to cosmetic piercing are rare, but can cause
      significant illness. We report the investigation and management of a point-source
      outbreak that occurred during a Black Friday promotional event in North West
      England. Methods: Outbreak investigation was led by Public Health England, and
      included active case finding among individuals pierced at a piercing premises
      between 25/11/2016 (Black Friday) and 7/12/2016. Detailed epidemiological,
      environmental (including inspection and sampling), and microbiological
      investigation was undertaken. Results: During the Black Friday event
      (25/11/2016), 45 people were pierced (13 by a newly-appointed practitioner).
      Eleven cases were identified (7 microbiologically-confirmed, 2 probable, and 2
      possible). All cases had clinical signs of infection around piercing sites, and
      five required surgical intervention, with varying degrees of post-operative
      disfigurement. All confirmed and probable cases had a scaffold piercing placed
      with a guide bar by the newly-appointed practitioner. Pseudomonas aeruginosa,
      indistinguishable at nine-locus variable-number tandem repeat loci, was isolated
      from four of the confirmed cases, and from pre- and post-flush samples from five
      separate water taps (three sinks) in the premises. Water samples taken after
      remedial plumbing work confirmed elimination of Pseudomonas contamination.
      Discussion: Although high levels of Pseudomonas water contamination and some poor
      infection control procedures were identified, infection appeared to require
      additional exposure to an inexperienced practitioner, and the more invasive
      scaffold piercing. A proactive collaborative approach between piercers and health
      and environmental officials is required to reduce outbreak risk, particularly
      when unusually large events are planned.

PMID- 29188132
TI  - What Do We Mean by 'Community Resilience'? A Systematic Literature Review of How
      It Is Defined in the Literature.
AB  - Background: Government, industry and charitable organisations have an increasing
      focus on programs intended to support community resilience to disasters. But has
      consensus been reached as to what defines 'community resilience' and what its
      core characteristics are? Methods: We undertook a systematic literature review of
      definitions of community resilience related to disasters. We conducted an
      inductive thematic analysis of the definitions and descriptions that we
      identified, in order to determine the proposed characteristics of community
      resilience prior to, during and after a disaster. Results: We identified 80
      relevant papers. There was no evidence of a common, agreed definition of
      community resilience. In spite of this, evidence was found of nine core elements
      of community resilience that were common among the definitions. The core elements
      were: local knowledge, community networks and relationships, communication,
      health, governance and leadership, resources, economic investment, preparedness,
      and mental outlook. Within these core elements, we identified 19 sub-elements
      linked to community resilience. Conclusion: Our findings show that community
      resilience remains an amorphous concept that is understood and applied
      differently by different research groups. Yet in spite of the differences in
      conception and application, there are well-understood elements that are widely
      proposed as important for a resilient community. A focus on these individual
      elements may be more productive than attempting to define and study community
      resilience as a distinct concept.

PMID- 29188133
TI  - Discussion Informed by Recurrent Lessons from a Systematic Review on Targeting
      Practices in Urban Humanitarian Crises.
AB  - Introduction: Urbanization has challenged many humanitarian practices given the
      complexity of cities. Urban humanitarian crises have similarly made identifying
      vulnerable populations difficult. As humanitarians respond to cities with chronic
      deficiencies in basic needs stressed by a crisis, identifying and prioritizing
      the most in need populations with finite resources is critical. Methods: The full
      systematic review applied standard systematic review methodology that was
      described in detail, peer-reviewed, and published before the research was
      conducted.Results: While the science of humanitarian practice is still
      developing, a systematic review of targeting vulnerable populations in urban
      humanitarian crises shed some light on the evidence base to guide policy and
      practice. This systematic review, referenced and available online, led to further
      findings that did not meet the pre-defined inclusion and exclusion criteria for
      evidence set out in the full review but that the authors, in their expert
      opinion, believe provide valuable insight nonetheless given their recurrence.
      Discussion: These additional findings that did not meet criteria for evidence and
      formal inclusion in the full manuscript, but deemed valuable by the subject
      expert authors, are discussed in this commentary.

PMID- 29188134
TI  - Assessing the Prevalence of Risk Factors for Neglected Tropical Diseases in
      Brazos County, Texas.
AB  - Introduction: Although more than one billion people live at risk of neglected
      tropical diseases (NTDs) in areas of Asia, sub-Saharan Africa, and Latin America,
      the degree to which they burden countries like the U.S. is unclear. Even though
      many NTDs such as dengue, leishmaniasis, and Chagas disease are typically not
      endemic to the U.S., the possibility of their emergence is noteworthy, especially
      in states like Texas with high levels of poverty, large immigrant populations,
      geographic proximity to endemic areas, and a climate amenable to the vectors for
      these diseases. Despite the health threat that emerging NTDs may pose, little is
      known about the prevalence of risk factors for NTDs in the U.S. Methods: We
      tested the Community Assessment for Public Health Emergency Response (CASPER)
      method to assess the prevalence of risk factors for NTDs in Brazos County,
      Texas.Results: We found relatively low prevalence of risk factors related to
      travel (5.2% of respondents visited an endemic area in the previous 3 months);
      however, few respondents reported adherence to mosquito prevention, such as
      wearing long sleeves and long pants (14.1%, 95% CI: 13.9,14.4) and repellant
      containing DEET (13.5%, 95% CI: 13.2,13.7). Between 5.4% and 35.8% of respondents
      had a visible container (e.g., pet water dishes, flower pots, bird baths) that
      could support mosquito breeding. Discussion: CASPER findings present public
      health authorities with potential avenues for implementing health education and
      other interventions aimed at reducing exposure to risk factors for NTDs among
      Texas residents.

PMID- 29188136
TI  - Fetal Zika Virus Infection in Vietnam.
AB  - As of 13 July 2016, 13 countries have reported fetal Zika virus (ZIKV) infection.
      Here we report a case of fetal ZIKV infection that resulted from an infection
      originating in Vietnam.

PMID- 29188137
TI  - Listening to the Voices of the People: Community's Assessment of Disaster
      Responder Agency Performance During Disaster Situations in Rural Northern Ghana.
AB  - Introduction: In Northern Ghana, a combination of torrential rains coupled with
      the spilling of the Bagre dam in neighboring Burkina Faso in the past few years
      has resulted in perennial flooding of communities. This has often led to the
      National Disaster Management Organization (NADMAO) the main disaster responder
      agency in Ghana, being called upon to act. However affected communities have
      never had the opportunity to evaluate the activities of the agency. The aim of
      this study is therefore to assess the performance of the main responder agency by
      affected community members to improve on future disaster management. Methods: A
      mixed qualitative design employing a modified form of the community score card
      methodology and focus group discussions was conducted in the 4 most affected
      communities during the last floods of 2012 in the Kasena-Nankana West district of
      the Upper East Region of Northern Ghana. Community members comprising of chiefs,
      elders, assembly members, women groups, physically challenged persons, farmers,
      traders and youth groups formed a group in each of the four communities.
      Generation and scoring of evaluative indicators was subsequently performed by
      each group through the facilitation of trained research assistants. Four Focus
      group discussions (FGDs) were also conducted with the group members in each
      community to get an in-depth understanding of how the responder agency performed
      in handling disasters. Results: A total of four community score cards and four
      focus group discussions were conducted involving 48 community representatives.
      All four communities identified NADMO as the main responder agency during the
      last disaster. Indicators such as education/awareness, selection process of
      beneficiaries, networking/collaboration, timing, quantity of relief items,
      appropriateness, mode of distribution of relief items, investigation and overall
      performance of NADMO were generated and scored. The timing of response, quantity
      and appropriateness of relief items were evaluated as being poor whereas the
      overall performance of the responder agency was above average. Conclusion: NADMO
      was identified as the main responder agency during the last disasters with
      community members identifying education/awareness, selection process of
      beneficiaries, networking/collaboration, timing of response, quantity of relief
      items, appropriateness of relief items, mode of distribution of relief items,
      investigation and overall performance as the main evaluative indicators. The
      overall performance of NADMO was rated to be satisfactory. Key words: Kasena
      Nankana West district, NADMO, community score card, Rural Northern Ghana.

PMID- 29188135
TI  - Benefits of Prenatal Taurine Supplementation in Preventing the Onset of Acute
      Damage in the Mdx Mouse.
AB  - Introduction: Duchenne Muscular Dystrophy (DMD) is a debilitating muscle wasting
      disorder with no cure. Safer supplements and therapies are needed to improve the
      severity of symptoms, as severe side effects are associated with the only
      effective treatment, corticosteroids. The amino acid taurine has shown promise in
      ameliorating dystrophic symptoms in mdx mice, an animal model of DMD, however
      little work is in 21-28 (d)ay animals, the period of natural peak damage.
      Methods: This study compares the effect of prenatal taurine supplementation on
      tibialis anterior (TA) in situ contractile function, histopathological
      characteristics and the abundance of Ca2+-handling as well as pathologically
      relevant proteins in non-exercised mdx mice at 28 and 70 d. Results:
      Supplementation elevated TA taurine content by 25% (p<0.05), ameliorated in situ
      specific force by 60% (p<0.05) and improved histological characteristics in 28 d
      mdx mice; however no benefit was seen in 70 d mice, where background pathology
      was initially stable. Age specific effects in SERCA1, calsequestrin 1 (CSQ1),
      CSQ2, utrophin and myogenin protein abundances were seen between both 28 and 70 d
      mdx and mdx taurine-supplemented mice. Discussion: Considering these findings and
      that taurine is a relatively cost effective, readily accessible and side effect
      free dietary supplement, we propose further investigation into taurine
      supplementation during pregnancy in a protective capacity, reminiscent of folate
      in the prevention of spinal bifida.

PMID- 29188138
TI  - The Effect of Armed Conflict on the Utilization of Maternal Health Services in
      Uganda: A Population-based Study.
AB  - Introduction: Maternal mortality rates can be adversely affected by armed
      conflict, implying a greater level of vulnerability among women, and is often
      linked to the lack of or limited access to maternal healthcare during conflict.
      Previous research in Uganda has shown that armed conflict negatively impacts
      women's utilization of maternal healthcare services for a multitude of reasons at
      the individual, health-system and political levels. Methods: This study compared
      aggregated Demographic and Health Surveys data from 13 districts in Northern
      Uganda, a conflict-affected region, with data from the rest of the country, for
      the use of maternal healthcare services for the years 1988, 1995, 2000, 2006 and
      2011, using statistical analyses and logistic regression. Specific indicators for
      maternal healthcare utilization included contraceptive use, antenatal care,
      skilled assistance at birth and institutional delivery. Results: Use of
      contraception and institutional deliveries among women in Northern Uganda was
      significantly lower compared to the rest of the country. However, skilled
      assistance at birth among women in Northern Uganda was significantly higher.
      Conclusions: The findings in this study show that armed conflict can have a
      negative impact on aspects of maternal healthcare such as contraceptive use and
      institutional deliveries; however, other indicators such as skilled assistance at
      birth were seen to be better among conflict-affected populations. This reiterates
      the complex nature of armed conflict and the interplay of different factors such
      as conflict intensity, existing health systems and services, and humanitarian
      interventions that could influence maternal healthcare utilization. Key words:
      Armed conflict, maternal health utilization, Northern Uganda, contraception,
      skilled assistance at birth, antenatal care, institutional delivery.

PMID- 29188139
TI  - Adipose Tissue Metabolism and Cancer Progression: Novel Insights from Gut
      Microbiota?
AB  - Purpose of Review: Obesity is strongly associated with the development of several
      types of cancers. This review aims to discuss the recent key mechanisms and
      actors underlying the link between adipose tissue metabolism and cancer, and the
      unequivocal common mechanisms connecting gut microbes to adipose tissue and
      eventually cancer development. Recent Findings: Complex interactions among
      systemic and tissue-specific pathways are suggested to link obesity and cancer,
      involving endocrine hormones, adipokines, fatty acids, inflammation, metabolic
      alterations, and hypoxia. Emerging evidence also suggests that the gut
      microbiota, another key environmental factor, may be considered as a converging
      element. Studies have shown that cancer susceptibility may be induced in germ
      free mice colonized with the gut microbiota from high-fat diet-fed mice.
      Suggested mechanisms may involve inflammation, immunity changes, lipogenic
      substrates, and adipogenesis. Summary: Cancer development is a complex process
      that may be under the control of previously unthought factors such as the gut
      microbiota. Whether specific intervention targeting the gut microbiota may reduce
      adipose tissue-driven cancer is an interesting strategy that remains to be
      proven.

PMID- 29188140
TI  - Forelimb muscle and joint actions in Archosauria: insights from Crocodylus
      johnstoni (Pseudosuchia) and Mussaurus patagonicus (Sauropodomorpha).
AB  - Many of the major locomotor transitions during the evolution of Archosauria, the
      lineage including crocodiles and birds as well as extinct Dinosauria, were shifts
      from quadrupedalism to bipedalism (and vice versa). Those occurred within a
      continuum between more sprawling and erect modes of locomotion and involved
      drastic changes of limb anatomy and function in several lineages, including
      sauropodomorph dinosaurs. We present biomechanical computer models of two
      locomotor extremes within Archosauria in an analysis of joint ranges of motion
      and the moment arms of the major forelimb muscles in order to quantify
      biomechanical differences between more sprawling, pseudosuchian (represented the
      crocodile Crocodylus johnstoni) and more erect, dinosaurian (represented by the
      sauropodomorph Mussaurus patagonicus) modes of forelimb function. We compare
      these two locomotor extremes in terms of the reconstructed musculoskeletal
      anatomy, ranges of motion of the forelimb joints and the moment arm patterns of
      muscles across those ranges of joint motion. We reconstructed the three
      dimensional paths of 30 muscles acting around the shoulder, elbow and wrist
      joints. We explicitly evaluate how forelimb joint mobility and muscle actions may
      have changed with postural and anatomical alterations from basal archosaurs to
      early sauropodomorphs. We thus evaluate in which ways forelimb posture was
      correlated with muscle leverage, and how such differences fit into a broader
      evolutionary context (i.e. transition from sprawling quadrupedalism to erect
      bipedalism and then shifting to graviportal quadrupedalism). Our analysis reveals
      major differences of muscle actions between the more sprawling and erect models
      at the shoulder joint. These differences are related not only to the articular
      surfaces but also to the orientation of the scapula, in which extension/flexion
      movements in Crocodylus (e.g. protraction of the humerus) correspond to
      elevation/depression in Mussaurus. Muscle action is highly influenced by limb
      posture, more so than morphology. Habitual quadrupedalism in Mussaurus is not
      supported by our analysis of joint range of motion, which indicates that
      glenohumeral protraction was severely restricted. Additionally, some active
      pronation of the manus may have been possible in Mussaurus, allowing semi
      pronation by a rearranging of the whole antebrachium (not the radius against the
      ulna, as previously thought) via long-axis rotation at the elbow joint. However,
      the muscles acting around this joint to actively pronate it may have been too
      weak to drive or maintain such orientations as opposed to a neutral position in
      between pronation and supination. Regardless, the origin of quadrupedalism in
      Sauropoda is not only linked to manus pronation but also to multiple shifts of
      forelimb morphology, allowing greater flexion movements of the glenohumeral joint
      and a more columnar forelimb posture.

PMID- 29188141
TI  - The relationship between egg size and helper number in cooperative breeders: a
      meta-analysis across species.
AB  - Background: Life history theory predicts that mothers should adjust reproductive
      investment depending on benefits of current reproduction and costs of reduced
      future reproductive success. These costs and benefits may in turn depend on the
      breeding female's social environment. Cooperative breeders provide an ideal
      system to test whether changes in maternal investment are associated with the
      social conditions mothers experience. As alloparental helpers assist in offspring
      care, larger groups might reduce reproductive costs for mothers or alternatively
      indicate attractive conditions for reproduction. Thus, mothers may show reduced
      (load-lightening) or increased (differential allocation) reproductive investment
      in relation to group size. A growing number of studies have investigated how
      cooperatively breeding mothers adjust pre-natal investment depending on group
      size. Our aim was to survey these studies to assess, first, whether mothers
      consistently reduce or increase pre-natal investment when in larger groups and,
      second, whether these changes relate to variation in post-natal investment.
      Methods: We extracted data on the relationship between helper number and maternal
      pre-natal investment (egg size) from 12 studies on 10 species of cooperatively
      breeding vertebrates. We performed meta-analyses to calculate the overall
      estimated relationship between egg size and helper number, and to quantify
      variation among species. We also tested whether these relationships are stronger
      in species in which the addition of helpers is associated with significant
      changes in maternal and helper post-natal investment. Results: Across studies,
      there is a significant negative relationship between helper number and egg size,
      suggesting that in most instances mothers show reduced reproductive investment in
      larger groups, in particular in species in which mothers also show a significant
      reduction in post-natal investment. However, even in this limited sample,
      substantial variation exists in the relationship between helper number and egg
      size, and the overall effect appears to be driven by a few well-studied species.
      Discussion: Our results, albeit based on a small sample of studies and species,
      indicate that cooperatively breeding females tend to produce smaller eggs in
      larger groups. These findings on prenatal investment accord with previous studies
      showing similar load-lightening reductions in postnatal parental effort (leading
      to concealed helper effects), but do not provide empirical support for
      differential allocation. However, the considerable variation in effect size
      across studies suggests that maternal investment is mitigated by additional
      factors. Our findings indicate that variation in the social environment may
      influence life-history strategies and suggest that future studies investigating
      within-individual changes in maternal investment in cooperative breeders offer a
      fruitful avenue to study the role of adaptive plasticity.

PMID- 29188142
TI  - Characteristics and risk factors of rheumatoid arthritis in the United States: an
      NHANES analysis.
AB  - Background: We examined the United States National Health and Nutrition
      Examination Survey (NHANES) database to determine factors associated with
      rheumatoid arthritis (RA) in adults 20 to 55 years of age. Methods: NHANES data
      collected between 2007 and 2014, excluding the 2011-2012 period, were used.
      Subjects were divided into those with and without RA. Demographic, clinical, and
      lifestyle factors were compared between the groups. Results: After applying
      inclusion/exclusion criteria, 8,789 persons were included in the study (8,483
      without RA, 306 with RA). Multivariable analysis indicated that advanced age
      (odds ratio [OR] = 1.09, 95% CI [1.07-1.11], P < 0.001), regular smoking (OR =
      2.19, 95% CI [1.49-3.21], P < 0.001), diabetes (OR = 2.00, 95% CI [1.35-2.95], P
      = 0.001), obesity (reference, normal or underweight; OR = 3.31, 95% CI [2.05
      5.36], P < 0.001), and osteoporosis (OR = 3.68, 95% CI [1.64-8.22], P = 0.002)
      were positively associated with RA. Covered by health insurance (OR = 1.81, 95%
      CI [1.12-2.93], P = 0.016) and living in poverty (OR = 2.96, 95% CI [1.88-4.65],
      P < 0.001) were also associated with having RA. Mexican American, Hispanic white
      or other Hispanic ethnicity (reference, non-Hispanic white; OR = 0.54, 95% CI
      [0.31-0.96], P = 0.036), appropriate sleep duration (about 6-11 h, OR = 0.46, 95%
      CI [0.32-0.65], P < 0.001), and insufficient vitamin A intake (reference,
      recommended; OR = 0.70, 95% CI [0.50-0.98], P = 0.036) were negatively associated
      with RA. Discussion: Some factors associated with RA are potentially modifiable.

PMID- 29188143
TI  - The impact of self-incompatibility systems on the prevention of biparental
      inbreeding.
AB  - Inbreeding in hermaphroditic plants can occur through two different mechanisms:
      biparental inbreeding, when a plant mates with a related individual, or self
      fertilization, when a plant mates with itself. To avoid inbreeding, many
      hermaphroditic plants have evolved self-incompatibility (SI) systems which
      prevent or limit self-fertilization. One particular SI system-homomorphic SI-can
      also reduce biparental inbreeding. Homomorphic SI is found in many angiosperm
      species, and it is often assumed that the additional benefit of reduced
      biparental inbreeding may be a factor in the success of this SI system. To test
      this assumption, we developed a spatially-explicit, individual-based simulation
      of plant populations that displayed three different types of homomorphic SI. We
      measured the total level of inbreeding avoidance by comparing each population to
      a self-compatible population (NSI), and we measured biparental inbreeding
      avoidance by comparing to a population of self-incompatible plants that were free
      to mate with any other individual (PSI). Because biparental inbreeding is more
      common when offspring dispersal is limited, we examined the levels of biparental
      inbreeding over a range of dispersal distances. We also tested whether the
      introduction of inbreeding depression affected the level of biparental inbreeding
      avoidance. We found that there was a statistically significant decrease in
      autozygosity in each of the homomorphic SI populations compared to the PSI
      population and, as expected, this was more pronounced when seed and pollen
      dispersal was limited. However, levels of homozygosity and inbreeding depression
      were not reduced. At low dispersal, homomorphic SI populations also suffered
      reduced female fecundity and had smaller census population sizes. Overall, our
      simulations showed that the homomorphic SI systems had little impact on the
      amount of biparental inbreeding in the population especially when compared to the
      overall reduction in inbreeding compared to the NSI population. With further
      study, this observation may have important consequences for research into the
      origin and evolution of homomorphic self-incompatibility systems.

PMID- 29188144
TI  - An efficient pipeline to generate data for studies in plastid population genomics
      and phylogeography.
AB  - Premise of the study: Seed dispersal contributes to gene flow and is responsible
      for colonization of new sites and range expansion. Sequencing chloroplast
      haplotypes offers a way to estimate contributions of seed dispersal to population
      genetic structure and enables studies of population history. Whole-genome
      sequencing is expensive, but resources can be conserved by pooling samples.
      Unfortunately, haplotype associations among single-nucleotide polymorphisms
      (SNPs) are lost in pooled samples, and treating SNP allele frequencies as
      independent markers provides biased estimates of genetic structure. Methods: We
      developed sampling methodologies and an application, CallHap, that uses a least
      squares algorithm to evaluate the fit between observed and predicted SNP allele
      frequencies from pooled samples based on haplotype network phylogeny structure,
      thus enabling pooling for chloroplast sequencing for large-scale studies of
      chloroplast genomic variation. This method was tested using artificially
      constructed test networks and pools, and pooled samples of Lasthenia californica
      (California goldfields) from southern Oregon, USA. Results: CallHap reliably
      recovered network topologies and haplotype frequencies from pooled samples.
      Discussion: The CallHap pipeline allows for the efficient use of resources for
      estimation of genetic structure for studies using nonrecombining haplotypes such
      as intraspecific variation in chloroplast, mitochondrial, bacterial, or viral
      DNA.

PMID- 29188145
TI  - A three-dimensional spatial mapping approach to quantify fine-scale heterogeneity
      among leaves within canopies.
AB  - Premise of the study: The three-dimensional structure of tree canopies creates
      environmental heterogeneity, which can differentially influence the chemistry,
      morphology, physiology, and/or phenology of leaves. Previous studies that
      subdivide canopy leaves into broad categories (i.e., "upper/lower") fail to
      capture the differences in microenvironments experienced by leaves throughout the
      three-dimensional space of a canopy. Methods: We use a three-dimensional spatial
      mapping approach based on spherical polar coordinates to examine the fine-scale
      spatial distributions of photosynthetically active radiation (PAR) and the
      concentration of ultraviolet (UV)-absorbing compounds (A300) among leaves within
      the canopies of black mangroves (Avicennia germinans). Results: Linear
      regressions revealed that interior leaves received less PAR and produced fewer UV
      absorbing compounds than leaves on the exterior of the canopy. By allocating more
      UV-absorbing compounds to the leaves on the exterior of the canopy, black
      mangroves may be maximizing UV-protection while minimizing biosynthesis of UV
      absorbing compounds. Discussion: Three-dimensional spatial mapping provides an
      inexpensive and portable method to detect fine-scale differences in environmental
      and biological traits within canopies. We used it to understand the relationship
      between PAR and A300, but the same approach can also be used to identify traits
      associated with the spatial distribution of herbivores, pollinators, and
      pathogens.

PMID- 29188146
TI  - Characterization and development of EST-derived SSR markers in Sinowilsonia
      henryi (Hamamelidaceae).
AB  - Premise of the study: Polymorphic microsatellite markers were developed to reveal
      the genetic diversity of extant populations and the mating system of Sinowilsonia
      henryi (Hamamelidaceae). Methods and Results: In this study, nuclear simple
      sequence repeat (SSR) markers were developed using the Illumina high-throughput
      sequencing technique (RNA-Seq). The de novo-assembled transcriptome generated a
      total of 64,694 unique sequences with an average length of 601 bp. A total of
      2941 microsatellite loci were detected. Of the 121 tested loci, 13 loci were
      polymorphic and eight were monomorphic among 72 individuals representing three
      natural populations of the species. The number of alleles per locus ranged from
      one to four, and the observed and expected heterozygosity at population level
      were 0.00-1.00 and 0.10-0.66, respectively. Conclusions: The developed expressed
      sequence tag (EST)-SSRs will be useful for studying genetic diversity of S.
      henryi as well as assessing the mating system among Sinowilsonia species.

PMID- 29188147
TI  - Development and characterization of EST-SSR markers for Ottelia acuminata var.
      jingxiensis (Hydrocharitaceae).
AB  - Premise of the study: Simple sequence repeat (SSR) markers were derived from
      transcriptomic data for Ottelia acuminata (Hydrocharitaceae), a species
      comprising five endemic and highly endangered varieties in China. Methods and
      Results: Sixteen novel SSR markers were developed for O. acuminata var.
      jingxiensis. One to eight alleles per locus were found, with a mean of 2.896. The
      observed and expected heterozygosity ranged from 0.000 to 1.000 and 0.000 to
      0.793, respectively. Interestingly, in cross-varietal amplification, 13 out of
      the 16 loci were successfully amplified in O. acuminata var. acuminata, and 12
      amplified in each of the other three varieties of O. acuminata. Conclusions:
      These newly developed SSR markers will facilitate further study of genetic
      variation and provide important genetic data needed for appropriate conservation
      of natural populations of all varieties of O. acuminata.

PMID- 29188148
TI  - Development, characterization, and cross-amplification of 16 microsatellite
      primers for Atriplex tatarica (Amaranthaceae).
AB  - Premise of the study: Microsatellite primers were developed to characterize the
      genetic diversity and structure of the annual herb Atriplex tatarica
      (Amaranthaceae) and to facilitate ecological and evolutionary studies of A.
      tatarica and its relatives. Methods and Results: Sixteen novel microsatellite
      primers were developed for A. tatarica based on high-throughput sequencing of
      enriched libraries. All markers were polymorphic, with the number of alleles per
      locus ranging from three to 25 and observed and expected heterozygosity ranging
      from 0.08 to 0.74 and 0.10 to 0.87, respectively. In addition, some of these loci
      were successfully amplified and showed polymorphisms in four Atriplex and seven
      Chenopodium species. Conclusions: The microsatellite markers published here will
      be useful in assessing genetic diversity, structure, and gene flow within and
      across populations of A. tatarica, as well as in other species of Atriplex and
      the related genus Chenopodium.

PMID- 29188149
TI  - Isolation and characterization of microsatellite primers for the critically
      endangered shrub Styphelia longissima (Ericaceae).
AB  - Premise of the study: Microsatellite markers were developed for population
      genetic analysis in the rare shrub Styphelia longissima (Ericaceae). Methods and
      Results: We generated ca. 2.5 million sequence reads using a Personal Genome
      Machine semiconductor sequencer. Using the QDD pipeline, we designed primers for
      >12,000 sequences with PCR product lengths of 80-480 bp. From these, 30 primer
      pairs were selected and screened using PCR; of these, 16 loci were found to be
      polymorphic, four loci were monomorphic, and 10 loci did not amplify reliably for
      S. longissima. For a sample of 57 plants from the only known population, the
      number of alleles observed for these 16 loci ranged from two to 21 and expected
      heterozygosity ranged from 0.49 to 0.91. These markers were also amplified in
      Astroloma xerophyllum, a closely related species. Conclusions: These markers will
      be used to characterize population genetic variation, spatial genetic structure,
      mating system parameters, and dispersal to aid in the management and conservation
      of the rare shrub S. longissima.

PMID- 29188150
TI  - A Rare Case of Unresectable Adenoid Cystic Carcinoma of the Nasopharynx Treated
      with Intensity Modulated Proton Therapy.
AB  - Adenoid cystic carcinoma (ACC) is generally treated with surgical resection
      followed by postoperative radiotherapy. In cases where surgical management is
      precluded due to the location of the tumor and/or patient factors, radiation
      therapy can be offered to achieve local control. Here, we present a case of
      unresectable Stage T4N0 ACC of the nasopharynx with skull base and intracranial
      extension treated with intensity modulated proton therapy (IMPT), which achieved
      good local control with no significant late toxicity.

PMID- 29188151
TI  - Arachnoid Cyst and Psychosis.
AB  - Few case reports discuss suspected psychiatric disturbances secondary to
      arachnoid cysts. To the best of our knowledge, psychosis from arachnoid cysts has
      not been reported in the recent literature. This case report discusses our
      experience with a 55-year-old male patient who manifested multiple psychotic
      episodes suspected in association with an arachnoid cyst. During the initial
      examinations, a computed tomography (CT) scan of his head revealed a relatively
      large left anterior superior arachnoid cyst with a mass effect on the frontal
      lobe. Despite multiple trials of combinations of mood stabilizers and
      psychotropic medications, the patient continued to deteriorate. We ordered a
      repeat CT of his head along with a magnetic resonance image and consulted a
      neurosurgeon for a possible surgical intervention. The neurosurgeon concluded
      that the patient's psychiatric symptoms were unrelated to the arachnoid cyst.
      While we were unable to determine the etiology of our patient's psychosis, we
      believe that the arachnoid cyst played at least some part, as evidenced by
      reports in the literature. Future advancements in radiological technology may
      allow for a better exploration of the causal relationship between psychiatric
      illnesses and brain lesions.

PMID- 29188152
TI  - Astragalus Tuberculosis: A Case Report and Review of the Literature.
AB  - Osteo-articular tuberculosis continues to be a major global pandemic, with its
      greatest impact in the third-world countries. Among osteo-articular tuberculosis,
      plantar localisation, particularly isolated involvement of the talus is an
      extremely rare event. We discuss the case of a 20-year-old male diagnosed with
      isolated tuberculosis of right talus without the radiological involvement of the
      distal tibia, fibula or calcaneum. The diagnosis was made with the help of
      magnetic resonance imaging and confirmed through core biopsy of the talus. He was
      treated with multi-drug antitubercular chemotherapy and ankle immobilization with
      protected weight bearing with good results.

PMID- 29188153
TI  - A Posterior Circulation Stroke Presenting with Isolated Truncal Ataxia.
AB  - Vertebral artery dissection is an infrequent and often misdiagnosed cause of
      stroke. In this case report, we describe a patient with a posterior circulation
      stroke caused by a vertebral artery dissection, who presented to the emergency
      department with isolated truncal ataxia. This case emphasizes the importance of
      obtaining a thorough history and physical exam for all neurologic complaints,
      including a careful ambulation assessment.

PMID- 29188154
TI  - Somatostatin Receptor Avidity in Gastrointestinal Stromal Tumors: Theranostic
      Implications of Gallium-68 Scan and Eligibility for Peptide Receptor Radionuclide
      Therapy.
AB  - This manuscript reports on a patient with a metastatic gastrointestinal stromal
      tumor (GIST) refractory to standard first-line treatment, who underwent a gallium
      68 scan based on pre-clinical data of somatostatin receptor (SSTR) expression in
      such tumors. The gallium-68 DOTATATE scan determined significant somatostatin
      receptor avidity as hypothesized, suggesting that this imaging modality may be
      used as an option for diagnostic and follow-up purposes in GIST patients. In
      addition, peptide receptor-mediated radiotherapy (177Lu-PPRT) via SSTR may
      provide a novel treatment strategy in carefully selected SSTR-avid GIST patients
      with thyrosine kinase inhibitor (TKI)-resistant tumors such as this case, and
      this warrants further investigation in novel clinical trial concepts.

PMID- 29188155
TI  - Abdominal Drains Retrieved Laparoscopically 15 Years Post Laparotomy.
AB  - A retained intra-abdominal foreign body is a common occurrence that is frequently
      underreported due to its medicolegal implications. Sponges, gauzes, surgical
      instruments, abdominal drains, etc. have been reported in the literature. The
      most common presentation for a retained intra-abdominal foreign body is
      postoperative abdominal infections or bleeding, frequently seen in the immediate
      postoperative period. Most of these foreign bodies are removed by exploratory
      laparotomy owing to recent abdominal surgeries or presentation as complicated
      abdominal masses. Here, we report a case with retained intra-abdominal drains for
      15 years with minimal symptoms presenting as an intermittent abdominal pain; the
      drains were removed using laparoscopic intervention.

PMID- 29188156
TI  - Hypoglycemia-associated In-stent Thrombosis: Are We Doing Too Much?
AB  - Diabetes mellitus is one of the most common modifiable risk factors for coronary
      artery disease, and its prevalence is rising globally. Persistent hyperglycemia
      has a well-established cardiovascular risk, and its treatment plays an important
      role in the prevention of future cardiovascular events. While we improved
      microvascular complications such as retinopathy, nephropathy, and neuropathy by
      stringent blood glucose control, the cardiovascular morbidity and mortality in
      diabetics remain high. Hypoglycemia, on the other hand, is an important side
      effect of pharmaceutical blood glucose control, especially those who are treated
      with insulin. Here, we report the case of a 38-year-old man with type 1 diabetes
      presenting twice with acute ST-elevation myocardial infarction, both in the
      setting of documented hypoglycemia. There are reported cases of acute
      cardiovascular events or silent myocardial ischemia associated with hypoglycemia,
      and we wish to raise awareness for clinicians who treat this special population
      of patients.

PMID- 29188158
TI  - Fulminant Hepatic Failure and Fatal Cerebral Edema Following Clostridium
      perfringens Bacteremia: Case Report and Review of Literature.
AB  - Clostridium perfringens (CP) bacteremia is a rare but rapidly fatal infection.
      Only 36 cases of CP bacteremia with gas containing liver abscesses on image
      studies have been reported in the literature since 1990. In this report, we
      describe a 65-year-old diabetic male with CP bacteremia which progressed into
      fulminant hepatic failure with subsequent fatal cerebral edema.

PMID- 29188157
TI  - Predicting Quality of Life Changes in Hemodialysis Patients Using Machine
      Learning: Generation of an Early Warning System.
AB  - Objective To predict changes in the quality of life scores of hemodialysis
      patients for the coming month and the development of an early warning system
      using machine learning Methods It was a prospective cohort study (one-month
      duration) at the dialysis center of a tertiary care hospital in Pakistan. The
      study started on 1st October 2016. About 78 patients have been enrolled till now.
      Bachelor of Medicine and Bachelor of Surgery (MBBS) qualified doctors
      administered a proforma with demographics and the validated Urdu version of World
      Health Organization Quality Of Life-BREF (WHOQOL-BREF). It was to be repeated
      after one month to the same patient by the same investigator. Simple statistics
      were computed using SPSS version 24 (IBM Corp., Armonk, NY) while machine
      learning was performed using R (version 3.0) and Orange (version 3.1). Results
      Using machine learning algorithms, two models (classification tree and Naive
      Bayes) were generated to predict an increase or decrease of 5% in a patient's
      WHOQOL-BREF score over one month. The classification tree was selected as the
      most accurate model with an area under curve (AUC) of 83.3% (accuracy: 81.9%) for
      the prediction of 5% increase in QOL and an AUC of 76.2% (accuracy: 81.8%) for
      the prediction of 5% decrease in QOL over the coming month. The factors
      associated with an increase of QOL by 5% or more over the next month included
      younger age (<19 years) and higher iron sucrose doses (>278mg/month). Drops in
      psychological, physical, and social domain scores lead to a decrease of 5% or
      more in QOL scores over the following month. Conclusion An early warning system,
      dialysis data interpretation for algorithmic-prediction on quality of life (DIAL)
      was built for the early detection of deteriorating QOL scores in the hemodialysis
      population using machine learning algorithms. The model pointed out that working
      on psychological and environmental domains, in particular, may prevent the drop
      in QOL scores from occurring. DIAL, if implemented on a larger scale, is expected
      to help patients in terms of ensuring a better QOL and in reducing the financial
      burden in the long term.

PMID- 29188159
TI  - Three-Dimensional Computed Tomography Reconstruction for Revision
      Parathyroidectomy.
AB  - A 57-year-old man presented with persistent hyperparathyroidism following primary
      parathyroidectomy. A four-dimensional computed tomography scan with three
      dimensional reconstruction showed two parathyroid glands (one right and one left)
      and anatomic variation from previous surgery. Revision surgery was performed
      revealing the parathyroid glands as expected from the preoperative three
      dimensional reconstruction. After surgery, the patient recovered well, and
      preoperative symptoms resolved. The use of three-dimensional computed tomography
      reconstruction provided accurate localization of the parathyroid glands and
      surrounding anatomic structures. This resulted in decreased preoperative planning
      cost, operative time, and estimated blood loss typical for patients who have
      multiple preoperative imaging studies.

PMID- 29188160
TI  - Severe Hyperthyroidism Masquerading as Acute Bulbar Weakness.
AB  - The stroke occurs in nearly 800,000 patients per year in the United States with
      significant morbidity if not treated and managed in a time sensitive manner.
      Acute bulbar weakness can be a common presenting manifestation of acute stroke
      and transient ischemic attack. However, up to 30% of the patients presenting with
      symptoms concerning for stroke could be displaying a disease process that mimics
      the stroke. These disorders include hypoglycemia, seizures, complicated
      migraines, and endocrinopathies such as thyroid disease. If neuroimaging fails to
      show evidence of an acute infarct, these stroke mimics should be considered. When
      acute bulbar weakness occurs in the setting of severe hyperthyroidism, the
      treatment of this process can result in rapid improvement of symptoms.

PMID- 29188161
TI  - An Invasive Case of Left-Sided Endocarditis Caused by Pseudomonas aeruginosa in a
      Patient with History of Intravenous Drug Abuse.
AB  - Infective endocarditis, caused by Pseudomonas aeruginosa, is rarely seen in
      clinical practice. It has been reported mainly in intravenous drug abusers
      (IVDA). We present a case of a 63-year-old male who presented with abdominal pain
      and fever. Computed tomography (CT) abdomen showed splenic and renal infarct. The
      blood culture grew Pseudomonas aeruginosa. A transthoracic echocardiogram showed
      aortic insufficiency with 13 mm mobile vegetation. The patient was started on
      ceftazidime and tobramycin and, later on, surgery was done for aortic valve
      replacement. His stay was complicated by multiple hemorrhagic emboli in the
      brain. This case highlights the importance of the early diagnosis and management
      of infective endocarditis caused by Pseudomonas aeruginosa.

PMID- 29188162
TI  - Obstructive Sleep Apnea: An Unusual Cause of Hemorrhagic Stroke.
AB  - Stroke is one of the most common causes of mortality and morbidity worldwide.
      Hemorrhagic stroke comprises 10-20% of strokes. Here, we present a case report of
      hemorrhagic stroke that may have been secondary to untreated Obstructive Sleep
      Apnea (OSA) in a young man with no other cardiovascular risk factors or features
      of metabolic syndrome. A 32-year-old man was admitted for hemorrhagic stroke. An
      initial thorough workup for the etiology of stroke was inconclusive. Eventually,
      a polysomnography was done, which demonstrated OSA suggesting that untreated OSA
      may have contributed to his stroke. OSA may cause hemorrhagic stroke by nocturnal
      blood pressure surge. So, all physicians should consider doing polysomnography
      for unexplained hemorrhagic stroke or in patients at risk. Diagnosing and
      treating OSA would be critical in preventing hemorrhagic stroke and its
      recurrences.

PMID- 29188163
TI  - Notalgia Paresthetica: A Novel Approach to Treatment with Cryolipolysis.
AB  - Notalgia paresthetica, a neurosensory syndrome that typically occurs on the upper
      back, has multiple clinical symptoms with variable degrees of expression in each
      individual afflicted with the condition. The involved site is usually
      hyperpigmented and is associated with burning, coldness, hypoesthesia, increased
      pain, pruritus and/or tingling. In the affected area, the number of nerve fibers
      may be increased and the cutaneous sensory nerves are altered secondary to
      localized impingement, central injury, or both. Although multiple therapeutic
      approaches for notalgia paresthetica have been described, none specifically
      address the essential pathogenesis of the condition-the altered cutaneous nerves.
      Cryolipolysis is a well-tolerated nonsurgical technique to reduce the
      subcutaneous fat layer. Selective apoptosis of adipocytes occurs since the lipid
      rich fat cells are more susceptible to cold injury than the surrounding water
      rich cells. Not only a marked decrease in pain sensitivity but also a sustained
      reduction in the density of myelinated and unmyelinated cutaneous nerves has been
      observed in cryolipolysis-treated skin. Therefore, cryolipolysis is a logical
      approach to the treatment of notalgia paresthetica. One or more cryolipolysis
      treatments may be necessary for complete or partial resolution of the
      individual's notalgia paresthetica-related cutaneous symptoms. In conclusion,
      evaluation of cryolipolysis as a noninvasive treatment of patients with notalgia
      paresthetica is warranted.

PMID- 29188164
TI  - Developing an Undergraduate Ultrasound Curriculum: A Needs Assessment.
AB  - Background The introduction of ultrasound into the undergraduate medical school
      curriculum is gaining momentum in North America. At present, many institutions
      are teaching ultrasound to undergraduate medical students using a traditional
      framework designed to instruct practicing clinicians, or have modeled the
      curriculum on other universities. This approach is not based on educational needs
      or supported by evidence. Methods Using a descriptive, cross-sectional survey of
      stakeholder groups, we assessed the perceived relevance of various ultrasound
      skills and the attitude towards implementing an undergraduate ultrasound
      curriculum at our university. Results One hundred and fifty survey respondents
      representing all major stakeholder groups participated. All medical students, 97%
      of residents and 82% of educators agreed that the introduction of an ultrasound
      curriculum would enhance medical students' understanding of anatomy and
      physiology. All clinical medical students and residents, 92% of preclinical
      medical students, and 82% of educators agreed that the curriculum should also
      include clinical applications of ultrasound. Participants also indicated their
      preferences for specific curriculum content based on their perceived needs.
      Conclusion An integrated undergraduate ultrasound curriculum composed of specific
      preclinical and clinical applications was deemed appropriate for our university
      following a comprehensive needs assessment. Other universities planning such
      curricula should consider employing a needs assessment to provide direction for
      curriculum need and content.

PMID- 29188165
TI  - Diffusion Tensor Imaging for Ruptured Cerebral Arteriovenous Malformation.
AB  - Non-ruptured arteriovenous malformations (AVMs) rarely cause tract disruption.
      Few studies have described how ruptured AVMs influence white matter (WM) tract
      morphology. We reviewed consecutive AVM cases treated at a tertiary care hospital
      where diffusion tensor imaging (DTI) tractography was obtained preoperatively.
      DTI was performed using the Synaptive Plan (Synaptive Medical Inc., Toronto,
      Canada). Quality control was performed by clinical application specialist.
      Perinidal fractional anisotropy (FA) value of corticospinal tracts (CST) was
      obtained. A reference FA value was obtained from the corresponding area on the
      contralateral side. Images were evaluated by a consultant neuroradiologist.
      Radiological findings were correlated with clinical findings. White matter
      morphology was described by a consultant neuroradiologist. All three cases
      included in the study had a history of haemorrhage in the past. Two patients had
      disruption of CST and presented with a significant neurological deficit. In one
      patient FA value of CST around the nidus was comparable to the contralateral side
      and did not show any neurological deficit. DTI integrated neuronavigation was
      used to plan the trajectory and complete resection of the AVM with excellent
      postoperative recovery.

PMID- 29188166
TI  - Tractography for Optic Radiation Preservation in Transcortical Approaches to
      Intracerebral Lesions.
AB  - We present a case of intraventricular meningioma resected via a transcortical
      approach using tractography for optic radiation and arcuate fasciculus
      preservation. We include a review of the literature. A 54-year-old woman with a
      history of breast cancer presented with gait imbalance. Workup revealed a mass in
      the atrium of the left lateral ventricle consistent with a meningioma. Whole
      brain automated diffusion tensor imaging (DTI) was used to plan a transcortical
      resection while sparing the optic radiations and arcuate fasciculus. A left
      posterior parietal craniotomy was performed using the Synaptive BrightMatterTM
      frameless navigation (Synaptive Medical, Toronto, Canada) to minimally disrupt
      the white matter pathways. A gross total resection was achieved. Postoperatively,
      the patient had temporary right upper extremity weakness, which improved, and her
      visual fields and speech remained intact. Pathology confirmed a World Health
      Organization (WHO) Grade I meningothelial meningioma. While a thorough
      understanding of cortical anatomy is essential for safe resection of eloquent or
      deep-seated lesions, significant variability in fiber bundles, such as optic
      radiations and the arcuate fasciculus, necessitates a more individualized
      understanding of a patient's potential surgical risk. The addition of enhanced
      DTI to the neurosurgeon's armamentarium may allow for more complete resections of
      difficult intracerebral lesions while minimizing complications, such as visual
      deficit.

PMID- 29188167
TI  - Reconstruction of the Ascending Reticular Activating System with Diffusion Tensor
      Tractography in Patients with a Disorder of Consciousness after Traumatic Brain
      Injury.
AB  - This work describes the reconstruction of the ascending reticular activating
      system (ARAS) with diffusion tensor tractography in three patients with altered
      consciousness after traumatic brain injury. A diffusion tensor tractography was
      performed in three patients with impaired consciousness after a severe traumatic
      brain injury. A 1.5 T scanner was used to obtain the tensor sequences; axial
      tensors were acquired. Post-processing was performed, and the mean fractional
      anisotropy (FA) values were recorded. The FA maps were used to do a manual
      tracing of the following regions of interest (ROIs): the ventromedial midbrain,
      the anterior thalamus, and the hypothalamus. Case 1 presented destruction of the
      right dorsal and ventral tegmental tracts as well as destruction of the right
      middle forebrain bundle, case 2 had destruction of the right dorsal tegmental
      tract, and case 3 had destruction of the bilateral ventral and dorsal tegmental
      tracts, as well as destruction of the right middle forebrain bundle. The affected
      fibers of the ascending reticular activating system with diffuse axonal injury
      and the FA values abnormalities in the ascending reticular activating system in
      three patients with a disorder of consciousness (DOC) after traumatic brain
      injury are described.

PMID- 29188168
TI  - IgG4-Related Pancreatitis and Immune Thrombocytopenia: A Case Report and
      Literature Review.
AB  - A patient with a prior diagnosis of IgG4-related autoimmune pancreatitis (AIP)
      presented four years later with severe prednisone resistant immune
      thrombocytopenia (ITP). Her case is reported and the scant literature of the very
      unusual possible association of IgG4-related AIP and ITP is reviewed. It is
      suggested that investigation for IgG4-related disease be part of the work-up of
      ITP.

PMID- 29188169
TI  - Analysis of Social Communication Questionnaire (SCQ) Screening for Children Less
      Than Age 4.
AB  - Purpose of Review: The Social Communication Questionnaire (SCQ) is a screener for
      Autism spectrum disorder (ASD) validated for age 4.0 +. There is a clinical need
      for an ASD screener for children beyond the 30-month age limit of the M-CHAT-R/F.
      We evaluate the literature on the use of the SCQ in children < 4.0 years. Recent
      Findings: Recent studies have used very large samples; included typically
      developing children, rather than just those with developmental disorders;
      compared the SCQ Lifetime and Current versions; and increased scrutiny of
      internal validity. Summary: The sensitivity-specificity balance in distinguishing
      between ASD and other developmental disorders is poor, which has led to
      development of abbreviated versions of the SCQ; however, sensitivity-specificity
      balance is better in a more general population. The SCQ Lifetime (not Current)
      version should be used. Future research relating should focus on further
      validation of the SCQ as a screener for children 30-48 months.

PMID- 29188170
TI  - The Role of Climate in the Epidemiology of Melioidosis.
AB  - Purpose of Review: Melioidosis epidemiology is susceptible to climate change
      through direct and indirect effects on human encounter with the causative agent,
      Burkholderia pseudomallei. This review describes the current depth of knowledge
      and recent advances in the understanding of this relationship and applies it to
      observations of melioidosis in Western Australia. Recent Findings: High maximum
      rainfall and dense cloud cover have been shown to predict environmental presence
      of B. pseudomallei and cases of melioidosis, probably through correspondingly
      high moisture levels in B. pseudomallei-receptive soils. Increased melioidosis
      cases have been observed following storms in Taiwan and cyclones in the
      Australian Northern Territory and strengthen the association between melioidosis
      and extreme weather events. Indirect weather effects contribute to bacterial
      exposure through mechanisms such as increasing B. pseudomallei output from water
      seeps after heavy rain or localised flooding. Climate and weather have been
      directly implicated in dissemination of B. pseudomallei and cases of melioidosis
      in several notable events in Western Australia. Over a 10-year surveillance
      period, the cases that lay in the path of a tropical cyclone co-located with
      cyclone systems that repeatedly crossed the Western Australian coast. Cyclone
      associated cases were caused by different B. pseudomallei MLST genotypes, arguing
      against airborne dissemination from a common source. Summary: Predicted increases
      in temperature, changes in global precipitation patterns and an increased
      incidence of extreme weather events are expected to change melioidosis
      epidemiology. Further studies of the physical geographic drivers of melioidosis
      will deepen understanding of the impact of climate on melioidosis.

PMID- 29188171
TI  - Managing persistent wound leakage after total knee and hip arthroplasty. Results
      of a nationwide survey among Dutch orthopaedic surgeons.
AB  - Background: Persistent wound leakage after joint arthroplasty is a scantily
      investigated topic, despite the claimed relation with a higher risk of
      periprosthetic joint infection. This results in a lack of evidence-based clinical
      guidelines for the diagnosis and treatment of persistent wound leakage after
      joint arthroplasty. Without such guideline, clinical practice in orthopaedic
      hospitals varies widely. In preparation of a nationwide multicenter randomized
      controlled trial on the optimal treatment of persistent wound leakage, we
      evaluated current Dutch orthopaedic care for persistent wound leakage after joint
      arthroplasty. Methods: We conducted a questionnaire-based online survey among all
      700 members of the Netherlands Orthopaedic Association, consisting of 23
      questions on the definition, classification, diagnosis and treatment of
      persistent wound leakage after joint arthroplasty. Results: The questionnaire was
      completed by 127 respondents, representing 68% of the Dutch hospitals that
      perform orthopaedic surgery. The results showed wide variation in the
      classification, definition, diagnosis and treatment of persistent wound leakage
      among Dutch orthopaedic surgeons. 56.7% of the respondents used a protocol for
      diagnosis and treatment of persistent wound leakage, but only 26.8% utilized the
      protocol in every patient. Most respondents (59.1%) reported a maximum period of
      persistent wound leakage before starting non-surgical treatment of 3 to 7 days
      after index surgery and 44.1% of respondents reported a maximum period of wound
      leakage of 10 days before converting to surgical treatment. Conclusions: The wide
      variety in clinical practice underscores the importance of developing an evidence
      based clinical guideline for the diagnosis and treatment of persistent wound
      leakage after joint arthroplasty. To this end, a nationwide multicenter
      randomized controlled trial will be conducted in the Netherlands, which may
      provide evidence on this important and poorly understood topic.

PMID- 29188172
TI  - Effect of Sonication on the Elution of Antibiotics from Polymethyl Methacrylate
      (PMMA).
AB  - Background: In the setting of prosthetic joint infections treated with a two
      stage procedure, spacers can be sonicated after removal. We hypothesize that the
      sonication process may cause an increased elution of antibiotics from the spacer,
      leading to elevated concentrations of antibiotics in the sonication fluid
      inhibiting bacterial growth. We aimed to evaluate in vitro the influence of
      sonication on the elution of antibiotics from polymethyl methacrylate (PMMA) over
      time and to determine whether these concentrations are above the minimum
      inhibitory concentrations (MIC) for microorganisms relevant in prosthetic joint
      infections. Methods: PMMA blocks impregnated with vancomycin, fosfomycin,
      gentamicin or daptomycin were incubated in phosphate-buffered saline (PBS) at 37
      degrees C for up to 6 weeks. PBS was changed once a week. Concentrations were
      determined from samples of each antibiotic every week, and after 5 minutes of
      sonication at 2, 4 and 6 weeks. Results: With sonication there was a trend toward
      an increase of the elution of antibiotics. This increase was significant for
      vancomycin at 2 and 4 weeks (p=0.008 and 0.002 respectively) and for fosfomycin
      at 2 weeks (p=0.01). Conclusion: The effect of sonication could play a role in
      clinical results, especially for daptomycin and gentamicin for which the MIC is
      close to the concentration of antibiotics at 4 and 6 weeks. We conclude that
      elution of antibiotics from PMMA along with the effect of sonication could
      inhibit bacterial growth from spacers, resulting in false negative results in the
      setting of two-stage exchange procedures for prosthetic joint infections.

PMID- 29188173
TI  - Influence of Sonication on Bacterial Regrowth from Antibiotic Loaded PMMA
      Scaffolds - An In-vitro Study.
AB  - Periprosthetic joint infection (PJI) is one of the most challenging complications
      after joint replacement. However, when treated correctly, chances of recovery are
      good. The most important step in correct diagnosis and management of PJI is the
      detection of the causative germ. In the last years, the use of sonication in the
      diagnostic process has become more important. However, this diagnostic
      methodology has been controversially discussed when used in combination with
      antibiotic loaded bone cement (PMMA), which is frequently used in joint
      replacement surgeries. The aim of this study was thus to analyse in vitro
      bacterial growth in sonication fluid cultures obtained from antibiotic loaded
      PMMA which were contaminated with various bacterial biofilms. Sonication fluid
      obtained from antibiotic loaded PMMA (Copal G+V and Copal G+C) and plain Palacos
      R (control) contaminated either with S. aureus, E. faecalis, S. sanguinis or
      P.acnes, were analysed for bacterial re-growth in a standardised in-vitro
      setting. In vitro bacterial growth was not interfered by released antibiotics
      from sonication of antibiotic loaded PMMA for S. aureus, E. faecalis and S.
      sanguinis. However, for P. acnes bacterial counts were affected by the released
      antibiotics as well as by the time delay between sonication and analysis. The in
      vitro data suggest sonication to be an easy and sensitive diagnostic modality to
      detect easy-to-detect bacteria, however, results are alarming for the difficult
      to-detect bacteria P. acnes, indicating that further attention and research is
      necessary to improve the detection of difficult-to-detect bacteria.

PMID- 29188174
TI  - Diagnosis Of Persistent Infection In Prosthetic Two-Stage Exchange: PCR analysis
      of Sonication fluid From Bone Cement Spacers.
AB  - Introduction: When treating periprosthetic joint infections with a two-stage
      procedure, antibiotic-impregnated spacers are used in the interval between
      removal of prosthesis and reimplantation. According to our experience, cultures
      of sonicated spacers are most often negative. The objective of our study was to
      investigate whether PCR analysis would improve the detection of bacteria in the
      spacer sonication fluid. Methods: A prospective monocentric study was performed
      from September 2014 to January 2016. Inclusion criteria were two-stage procedure
      for prosthetic infection and agreement of the patient to participate in the
      study. Beside tissues samples and sonication, broad range bacterial PCRs,
      specific S. aureus PCRs and Unyvero-multiplex PCRs were performed on the
      sonicated spacer fluid. Results: 30 patients were identified (15 hip, 14 knee and
      1 ankle replacements). At reimplantation, cultures of tissue samples and spacer
      sonication fluid were all negative. Broad range PCRs were all negative. Specific
      S. aureus PCRs were positive in 5 cases. We had two persistent infections and
      four cases of infection recurrence were observed, with bacteria different than
      for the initial infection in three cases. Conclusion: The three different types
      of PCRs did not detect any bacteria in spacer sonication fluid that was culture
      negative. In our study, PCR did not improve the bacterial detection and did not
      help to predict whether the patient will present a persistent or recurrent
      infection. Prosthetic 2-stage exchange with short interval and antibiotic
      impregnated spacer is an efficient treatment to eradicate infection as both
      culture- and molecular-based methods were unable to detect bacteria in spacer
      sonication fluid after reimplantation.

PMID- 29188176
TI  - Nano-sized Indocyanine Green J-aggregate as a One-component Theranostic Agent.
AB  - The development of biocompatiable efficient photothermal coupling agent (PCA) for
      image-guided photothermal therapy of cancer has gained increasing interests in
      recent years. Although various PCAs have been developed, the clinical
      translations of these materials have been largely hindered by the potential
      biosafety issues and challenges of scaling-up manufactures. In this research, we
      proposed nano-sized indocyanine green (ICG) J-aggregate (IJA) as a promising PCA
      which is fabricated by a very facile method using clinical-approved ICG as the
      only excipient. The as-prepared IJA remains stable in various solution and shows
      a ~115 nm red-shift in absorption peak compared to free ICG. Importantly, IJA can
      be disassociated into free ICG again after internalized into cells and exhibits
      high biosafety comparable to ICG. The IJA performs well for photothermal therapy
      both in vitro and in vivo. In addition, the IJA can also be used as a good
      photoacoustic contrast agent and internalization-responsive fluorescence probe.
      The facile preparation, high safety and excellent theranostic performance
      indicated that IJA might be a promising one-component agent for cancer
      theranostics.

PMID- 29188175
TI  - Current Progress of Virus-mimicking Nanocarriers for Drug Delivery.
AB  - Nanomedicines often involve the use of nanocarriers as a delivery system for
      drugs or genes for maximizing the therapeutic effect and/or minimizing the
      adverse effect. From drug administration to therapeutic activity, nanocarriers
      must evade the host's immune system, specifically and efficiently target and
      enter the cell, and release their payload into the cell cytoplasm by endosomal
      escape. These processes constitute the early infection stage of viruses. Viruses
      are a powerful natural nanomaterial for the efficient delivery of genetic
      information by sophisticated mechanisms. Over the past two decades, many virus
      inspired nanocarriers have been generated to permit successful drug and gene
      delivery. In this review, we summarize the early infection machineries of
      viruses, of which the part has so far been utilized for delivery systems.
      Furthermore, we describe basics and applications of the bio-nanocapsule, which is
      a hepatitis B virus-mimicking nanoparticle harboring nearly all activities
      involved in the early infection machineries (i.e., stealth activity, targeting
      activity, cell entry activity, endosomal escaping activity).

PMID- 29188177
TI  - Ultrasound-Stimulated Drug Delivery Using Therapeutic Reconstituted High-Density
      Lipoprotein Nanoparticles.
AB  - The abnormal tumor vasculature and the resulting abnormal microenvironment are
      major barriers to optimal chemotherapeutic drug delivery. It is well known that
      ultrasound (US) can increase the permeability of the tumor vessel walls and
      enhance the accumulation of anticancer agents. Reconstituted high-density
      lipoproteins (rHDL) nanoparticles (NPs) allow selective delivery of anticancer
      agents to tumor cells via their overexpressed scavenger receptor type B1 (SR-B1)
      receptor. The goal of this study is to investigate the potential of noninvasive
      US therapy to further improve delivery and tumor uptake of the payload from rHDL
      NPs, preloaded with an infrared dye (IR-780), aimed to establish a surrogate
      chemotherapeutic model with optical localization. Athymic nude mice were
      implanted orthotopically with one million breast cancer cells (MDA-MB-231/Luc).
      Three weeks later, animals were divided into seven groups with comparable mean
      tumor size: control, low, moderate, and high concentration of rHDL NPs alone
      groups, as well as these three levels of rHDL NPs plus US therapy groups (N = 7
      to 12 animals per group), where low, moderate and high denote 5, 10, and 50 ug of
      the IR-780 dye payload per rHDL NP injection, respectively. The US therapy system
      included a single element focused transducer connected in series with a function
      generator and power amplifier. A custom 3D printed cone with an acoustically
      transparent aperture and filled with degassed water allowed delivery of focused
      US energy to the tumor tissue. US exposure involved a pulsed sequence applied for
      a duration of 5 min. Each animal in the US therapy groups received a slow bolus
      co-injection of MB contrast agent and rHDL NPs. Animals were imaged using a whole
      body optical system to quantify intratumoral rHDL NP accumulation at baseline and
      again at 1 min, 30 min, 24 h, and 48 h. At 48 h, all animals were euthanized and
      tumors were excised for ex vivo analysis. We investigated a noninvasive optical
      imaging method for monitoring the effects of US-stimulated drug delivery of IR
      780 dye-loaded rHDL NPs in living animals. No change in optical imaging data was
      found in the control animals. However, there was considerable dye accumulation
      (surrogate drug) within 48 h in the low (5 ug), moderate (10 ug), and high (50
      ug) rHDL NP concentration-dosed group animals (p < 0.09). With US therapy added
      to the experimental protocol, there was an additional and significant increase in
      local tumor drug uptake at 48 h (p < 0.02). Optical image data collected from ex
      vivo tumor samples confirmed tumor retention of the IR-780 dye-loaded rHDL NPs
      and correlated positively with in vivo optical imaging results (R2 > 0.69, p <
      0.003). IR-780 dye extraction from the tumor tissue samples confirmed the in vivo
      and ex vivo US therapy findings. Overall, the addition of US therapy considerably
      improved local rHDL NP accumulation in tumor tissue. This study concludes that US
      mediated drug delivery can facilitate tumor uptake of rHDL NPs and more research
      is warranted to optimize the drug dosing schedule and the respective therapeutic
      protocols.

PMID- 29188178
TI  - Tumor shape pulmonary mucormycosis associated with sinonasal aspergillosis in a
      diabetic patient.
AB  - Mucormycosis is a rare and life-threatening fungal infection of the Mucorales
      order occurring mainly in immunosuppressed patients. The most common forms are
      rhinocerebral but pulmonary or disseminated forms may occur. We report the case
      of a 61-year-old patient in whom pulmonary mucormycosis was diagnosed during his
      first-ever episode of diabetic ketoacidosis. While receiving liposomal
      amphotericin B, a sinusal aspergillosis due to Aspergillus fumigatus occurred.
      Evolution was slowly favorable under antifungal tritherapy by liposomal
      amphotericin B, posaconazole and caspofungin.

PMID- 29188179
TI  - Development of a high efficiency integration system and promoter library for
      rapid modification of Pseudomonas putida KT2440.
AB  - Pseudomonas putida strains are highly robust bacteria known for their ability to
      efficiently utilize a variety of carbon sources, including aliphatic and aromatic
      hydrocarbons. Recently, P. putida has been engineered to valorize the lignin
      stream of a lignocellulosic biomass pretreatment process. Nonetheless, when
      compared to platform organisms such as Escherichia coli, the toolkit for
      engineering P. putida is underdeveloped. Heterologous gene expression in
      particular is problematic. Plasmid instability and copy number variance provide
      challenges for replicative plasmids, while use of homologous recombination for
      insertion of DNA into the chromosome is slow and laborious. Further, most
      heterologous expression efforts to date typically rely on overexpression of
      exogenous pathways using a handful of poorly characterized promoters. To improve
      the P. putida toolkit, we developed a rapid genome integration system using the
      site-specific recombinase from bacteriophage Bxb1 to enable rapid, high
      efficiency integration of DNA into the P. putida chromosome. We also developed a
      library of synthetic promoters with various UP elements, -35 sequences, and -10
      sequences, as well as different ribosomal binding sites. We tested these
      promoters using a fluorescent reporter gene, mNeonGreen, to characterize the
      strength of each promoter, and identified UP-element-promoter-ribosomal binding
      sites combinations capable of driving a ~150-fold range of protein expression
      levels. An additional integrating vector was developed that confers more robust
      kanamycin resistance when integrated at single copy into the chromosome. This
      genome integration and reporter systems are extensible for testing other genetic
      parts, such as examining terminator strength, and will allow rapid integration of
      heterologous pathways for metabolic engineering.

PMID- 29188180
TI  - Comparison of orthologous cyanobacterial aldehyde deformylating oxygenases in the
      production of volatile C3-C7 alkanes in engineered E. coli.
AB  - Aldehyde deformylating oxygenase (ADO) is a unique enzyme found exclusively in
      photosynthetic cyanobacteria, which natively converts acyl aldehyde precursors
      into hydrocarbon products embedded in cellular lipid bilayers. This capacity has
      opened doors for potential biotechnological applications aiming at biological
      production of diesel-range alkanes and alkenes, which are compatible with the
      nonrenewable petroleum-derived end-products in current use. The development of
      production platforms, however, has been limited by the relative inefficiency of
      ADO enzyme, promoting research towards finding new strategies and information to
      be used for rational design of enhanced pathways for hydrocarbon over-expression.
      In this work we present an optimized approach to study different ADO orthologs
      derived from different cyanobacterial species in an in vivo set-up in Escherichia
      coli. The system enabled comparison of alternative ADOs for the production
      efficiency of short-chain volatile C3-C7 alkanes, propane, pentane and heptane,
      and provided insight on the differences in substrate preference, catalytic
      efficiency and limitations associated with the enzymes. The work concentrated on
      five ADO orthologs which represent the most extensively studied cyanobacterial
      species in the field, and revealed distinct differences between the enzymes. In
      most cases the ADO from Nostoc punctiforme PCC 73102 performed the best in
      respect to yields and initial rates for the production of the volatile
      hydrocarbons. At the other extreme, the system harboring the ADO form
      Synechococcus sp. RS9917 produced very low amounts of the short-chain alkanes,
      primarily due to poor accumulation of the enzyme in E. coli. The ADOs from
      Synechocystis sp. PCC 6803 and Prochlorococcus marinus MIT9313, and the
      corresponding variant A134F displayed less divergence, although variation between
      chain-length preferences could be observed. The results confirmed the general
      trend of ADOs having decreasing catalytic efficiency towards precursors of
      decreasing chain-length, while expanding the knowledge on the species-specific
      traits, which may aid future pathway design and structure-based engineering of
      ADO for more efficient hydrocarbon production systems.

PMID- 29188181
TI  - Eliminating a global regulator of carbon catabolite repression enhances the
      conversion of aromatic lignin monomers to muconate in Pseudomonas putida KT2440.
AB  - Carbon catabolite repression refers to the preference of microbes to metabolize
      certain growth substrates over others in response to a variety of regulatory
      mechanisms. Such preferences are important for the fitness of organisms in their
      natural environments, but may hinder their performance as domesticated microbial
      cell factories. In a Pseudomonas putida KT2440 strain engineered to convert
      lignin-derived aromatic monomers such as p-coumarate and ferulate to muconate, a
      precursor to bio-based nylon and other chemicals, metabolic intermediates
      including 4-hydroxybenzoate and vanillate accumulate and subsequently reduce
      productivity. We hypothesized that these metabolic bottlenecks may be, at least
      in part, the effect of carbon catabolite repression caused by glucose or acetate,
      more preferred substrates that must be provided to the strain for supplementary
      energy and cell growth. Using mass spectrometry-based proteomics, we have
      identified the 4-hydroxybenzoate hydroxylase, PobA, and the vanillate
      demethylase, VanAB, as targets of the Catabolite Repression Control (Crc)
      protein, a global regulator of carbon catabolite repression. By deleting the gene
      encoding Crc from this strain, the accumulation of 4-hydroxybenzoate and
      vanillate are reduced and, as a result, muconate production is enhanced. In
      cultures grown on glucose, the yield of muconate produced from p-coumarate after
      36 h was increased nearly 70% with deletion of the gene encoding Crc (94.6 +/-
      0.6% vs. 56.0 +/- 3.0% (mol/mol)) while the yield from ferulate after 72 h was
      more than doubled (28.3 +/- 3.3% vs. 12.0 +/- 2.3% (mol/mol)). The effect of
      eliminating Crc was similar in cultures grown on acetate, with the yield from p
      coumarate just slightly higher in the Crc deletion strain after 24 h (47.7 +/-
      0.6% vs. 40.7 +/- 3.6% (mol/mol)) and the yield from ferulate increased more than
      60% after 72 h (16.9 +/- 1.4% vs. 10.3 +/- 0.1% (mol/mol)). These results are an
      example of the benefit that reducing carbon catabolite repression can have on
      conversion of complex feedstocks by microbial cell factories, a concept we posit
      could be broadly considered as a strategy in metabolic engineering for conversion
      of renewable feedstocks to value-added chemicals.

PMID- 29188182
TI  - A comprehensive evaluation of constraining amino acid biosynthesis in
      compartmented models for metabolic flux analysis.
AB  - Recent advances in the availability and applicability of genetic tools for non
      conventional yeasts have raised high hopes regarding the industrial applications
      of such yeasts; however, quantitative physiological data on these yeasts,
      including intracellular flux distributions, are scarce and have rarely aided in
      the development of novel yeast applications. The compartmentation of eukaryotic
      cells adds to model complexity. Model constraints are ideally based on
      biochemical evidence, which is rarely available for non-conventional yeast and
      eukaryotic cells. A small-scale model for 13C-based metabolic flux analysis of
      central yeast carbon metabolism was developed that is universally valid and does
      not depend on localization information regarding amino acid anabolism. The
      variable compartmental origin of traced metabolites is a feature that allows
      application of the model to yeasts with uncertain genomic and transcriptional
      backgrounds. The presented test case includes the baker's yeast Saccharomyces
      cerevisiae and the methylotrophic yeast Hansenula polymorpha. Highly similar flux
      solutions were computed using either a model with undefined pathway localization
      or a model with constraints based on curated (S. cerevisiae) or computationally
      predicted (H. polymorpha) localization information, while false solutions were
      found with incorrect localization constraints. These results indicate a
      potentially adverse effect of universally assuming Saccharomyces-like constraints
      on amino acid biosynthesis for non-conventional yeasts and verify the validity of
      neglecting compartmentation constraints using a small-scale metabolic model. The
      model was specifically designed to investigate the intracellular metabolism of
      wild-type yeasts under various growth conditions but is also expected to be
      useful for computing fluxes of other eukaryotic cells.

PMID- 29188184
TI  - UP Finder: A COBRA toolbox extension for identifying gene overexpression
      strategies for targeted overproduction.
AB  - Overexpression of key genes is a basic strategy for overproducing target products
      via metabolic engineering. Traditionally, identifying those key genes/pathways
      largely relies on the knowledge of biochemistry and bioinformatics. In this
      study, a modeling tool named UP Finder was developed to facilitate the rapid
      identification of gene overexpression strategies. It was based on the COBRA
      toolbox under MATLAB environment. All the key gene/pathway targets are identified
      in one click after simply loading a Systems Biology Markup Language model and
      specifying a metabolite as the targeted product. The outputs are also
      quantitatively ranked to show the preference for determining overexpression
      strategies in pathway design. Analysis examples for overproducing lycopene
      precursor in Escherichia coli and fatty acyl-ACP in the cyanobacterium
      Synechocystis sp. PCC 6803 by the UP Finder showed high degree of agreement with
      the reported key genes in the literatures.

PMID- 29188183
TI  - Isobutanol production in Synechocystis PCC 6803 using heterologous and endogenous
      alcohol dehydrogenases.
AB  - Isobutanol is a flammable compound that can be used as a biofuel due to its high
      energy density and suitable physical and chemical properties. In this study, we
      examined the capacity of engineered strains of Synechocystis PCC 6803 containing
      the alpha-ketoisovalerate decarboxylase from Lactococcus lactis and different
      heterologous and endogenous alcohol dehydrogenases (ADH) for isobutanol
      production. A strain expressing an introduced kivd without any additional copy of
      ADH produced 3 mg L-1 OD750-1 isobutanol in 6 days. After the cultures were
      supplemented with external addition of isobutyraldehyde, the substrate for ADH,
      60.8 mg L-1 isobutanol was produced after 24 h when OD750 was 0.8. The in vivo
      activities of four different ADHs, two heterologous and two putative endogenous
      in Synechocystis, were examined and the Synechocystis endogenous ADH encoded by
      slr1192 showed the highest efficiency for isobutanol production. Furthermore, the
      strain overexpressing the isobutanol pathway on a self-replicating vector with
      the strong Ptrc promoter showed significantly higher gene expression and
      isobutanol production compared to the corresponding strains expressing the same
      operon introduced on the genome. Hence, this study demonstrates that
      Synechocystis endogenous AHDs have a high capacity for isobutanol production, and
      identifies kivd encoded alpha-ketoisovalerate decarboxylase as one of the likely
      bottlenecks for further isobutanol production.

PMID- 29188185
TI  - Metabolic engineering of Schizosaccharomyces pombe via CRISPR-Cas9 genome editing
      for lactic acid production from glucose and cellobiose.
AB  - Modification of the Schizosaccharomyces pombe genome is often laborious, time
      consuming due to the lower efficiency of homologous recombination. Here, we
      constructed metabolically engineered S. pombe strains using a CRISPR-Cas9 system
      and also demonstrated D-lactic acid (D-LA) production from glucose and
      cellobiose. Genes encoding two separate pyruvate decarboxylases (PDCs), an L
      lactic acid dehydrogenase (L-LDH), and a minor alcohol dehydrogenase (SPBC337.11)
      were disrupted, thereby attenuating ethanol production. To increase the cellular
      supply of acetyl-CoA, an important metabolite for growth, we introduced genes
      encoding bacterial acetylating acetaldehyde dehydrogenase enzymes (Escherichia
      coli MhpF and EutE). D-LA production by the resulting strain was achieved by
      expressing a Lactobacillus plantarum gene encoding D-lactate dehydrogenase. The
      engineered strain efficiently consumed glucose and produced D-LA at 25.2 g/L from
      35.5 g/L of consumed glucose with a yield of 0.71 g D-LA / g glucose. We further
      modified this strain by expressing beta-glucosidase by cell surface display; the
      resulting strain produced D-LA at 24.4 g/L from 30 g/L of cellobiose in minimal
      medium, with a yield of 0.68 g D-LA / g glucose. To our knowledge, this study
      represents the first report of a S. pombe strain that was metabolically
      engineered using a CRISPR-Cas9 system, and demonstrates the possibility of
      engineering S. pombe for the production of value-added chemicals.

PMID- 29188188
TI  - Acute flank abdominal pain as the chief complaint of spontaneous adrenal
      hemorrhage secondary to metastatic lung cancer.

PMID- 29188187
TI  - Genome sequence and analysis of Escherichia coli production strain LS5218.
AB  - Escherichia coli strain LS5218 is a useful host for the production of fatty acid
      derived products, but the genetics underlying this utility have not been fully
      investigated. Here, we report the genome sequence of LS5218 and a list of large
      mutations and single nucleotide permutations (SNPs) relative to E. coli K-12
      strain MG1655. We discuss how genetic differences may affect the physiological
      differences between LS5218 and MG1655. We find that LS5218 is more closely
      related to E. coli strain NCM3722 and suspect that small genetic differences
      between K-12 derived strains may have a significant impact on metabolic
      engineering efforts.

PMID- 29188186
TI  - YaliBricks, a versatile genetic toolkit for streamlined and rapid pathway
      engineering in Yarrowia lipolytica.
AB  - Effective metabolic engineering of microorganisms relies on balanced expression
      of both heterologous and endogenous genes to channel metabolic flux towards
      products of interest while achieving reasonable biomass buildup. To facilitate
      combinatorial pathway engineering and facile genetic operation, we engineered a
      set of modular cloning vectors compatible with BioBrick standards, called
      YaliBricks, to allow for rapid assembly of multigene pathways with customized
      genetic control elements (promoters, intronic sequences and terminators) in the
      oleaginous yeast Yarrowia lipolytica. We established a sensitive luciferase
      reporter and characterized a set of 12 native promoters to expand the oleaginous
      yeast genetic toolbox for transcriptional fine-tuning. We harnessed the intron
      alternative splicing mechanism and explored three unique gene configurations that
      allow us to encode genetic structural variations into metabolic function. We
      elucidated the role of how these genetic structural variations affect gene
      expression. To demonstrate the simplicity and effectiveness of streamlined
      genetic operations, we assembled the 12 kb five-gene violacein biosynthetic
      pathway in one week. We also expanded this set of vectors to accommodate self
      cleavage ribozymes and efficiently deliver guide RNA (gRNA) for targeted genome
      editing with a codon-optimized CRISPR-Cas9 nuclease. Taken together, the tools
      built in this study provide a standard procedure to streamline and accelerate
      metabolic pathway engineering and genetic circuits construction in Yarrowia
      lipolytica.

PMID- 29188189
TI  - Formation of supported lipid bilayers of charged E. coli lipids on modified gold
      by vesicle fusion.
AB  - We describe a simple way of fusing E. coli lipid vesicles onto a gold surface.
      Supported lipid bilayers on metal surfaces are interesting for several reasons:
      transducing a biological signal to an electric readout, using surface analytical
      tools such as Surface Plasmon Resonance (SPR), Infrared Reflection Absorption
      Spectroscopy, Neutron Reflectivity or Electrochemistry. The most widely used
      method to prepare supported lipid membranes is fusion of preexisting liposomes.
      It is quite efficient on hydrophilic surfaces such as glass, mica or SiO2, but
      vesicle fusion on metals and metal oxide surfaces (as gold, titanium oxide or
      indium tin oxide), remains a challenge, particularly for vesicles containing
      charged lipids, as is the case of bacterial lipids. We describe a simple method
      based on modifying the gold surface with a charged mercaptopropionic acid self
      assembled monolayer and liposomes partially solubilized with detergent. The
      formed bilayers were characterized using a Quartz Crystal Microbalance with
      dissipation (QCM-D) and Atomic Force Microscopy (AFM). Some advantages of this
      protocol are that the stability of the self-assembled monolayer allows for
      repeated use of the substrate after detergent removal of the bilayer and that the
      amount of detergent required for optimal fusion can be determined previously
      using the lipid-detergent solubility curve.

PMID- 29188190
TI  - Quality control of oceanographic in situ data from Argo floats using
      climatological convex hulls.
AB  - A new method of identifying anomalous oceanic temperature and salinity (T/S) data
      from Argo profiling floats is proposed. The proposed method uses World Ocean
      Database 2013 climatology to classify good against anomalous data by using convex
      hulls. An n-sided polygon (convex hull) with least area encompassing all the
      climatological points is constructed using Jarvis March algorithm. Subsequently
      Points In Polygon (PIP) principle implemented using ray casting algorithm is used
      to classify the T/S data as within or without acceptable bounds. It is observed
      that various types of anomalies associated with the oceanographic data viz.,
      spikes, bias, sensor drifts etc can be identified using this method. Though
      demonstrated for Argo data it can be applied to any oceanographic data. *The
      patterns of variation of the parameter (temperature or salinity) corresponding to
      a particular depth, along the longitude or latitude can be used to build convex
      hulls.*This method can be effectively used for quality control by building Convex
      hulls for various observed depths corresponding to biogeochemical data which are
      sparsely observed.*This method has the advantage of treating the bulk of
      oceanographic in situ data in a single iteration which filters out anomalous
      data.

PMID- 29188192
TI  - Unlocking the epigenetic code of T cell exhaustion.

PMID- 29188191
TI  - Prostate cancer radiomics and the promise of radiogenomics.
AB  - Prostate cancer exhibits intra-tumoral heterogeneity that we hypothesize to be
      the leading confounding factor contributing to the underperformance of the
      current pre-treatment clinical-pathological and genomic assessment. These
      limitations impose an urgent need to develop better computational tools to
      identify men with low risk of prostate cancer versus others that may be at risk
      for developing metastatic cancer. The patient stratification will directly
      translate to patient treatments, wherein decisions regarding active surveillance
      or intensified therapy are made. Multiparametric MRI (mpMRI) provides the
      platform to investigate tumor heterogeneity by mapping the individual tumor
      habitats. We hypothesize that quantitative assessment (radiomics) of these
      habitats results in distinct combinations of descriptors that reveal regions with
      different physiologies and phenotypes. Radiogenomics, a discipline connecting
      tumor morphology described by radiomic and its genome described by the genomic
      data, has the potential to derive "radio phenotypes" that both correlate to and
      complement existing validated genomic risk stratification biomarkers. In this
      article we first describe the radiomic pipeline, tailored for analysis of
      prostate mpMRI, and in the process we introduce our particular implementations of
      radiomics modules. We also summarize the efforts in the radiomics field related
      to prostate cancer diagnosis and assessment of aggressiveness. Finally, we
      describe our results from radiogenomic analysis, based on mpMRI-Ultrasound (MRI
      US) biopsies and discuss the potential of future applications of this technique.
      The mpMRI radiomics data indicate that the platform would significantly improve
      the biopsy targeting of prostate habitats through better recognition of indolent
      versus aggressive disease, thereby facilitating a more personalized approach to
      prostate cancer management. The expectation to non-invasively identify habitats
      with high probability of housing aggressive cancers would result in directed
      biopsies that are more informative and actionable. Conversely, providing evidence
      for lack of disease would reduce the incidence of non-informative biopsies. In
      radiotherapy of prostate cancer, dose escalation has been shown to reduce
      biochemical failure. Dose escalation only to determinate prostate habitats has
      the potential to improve tumor control with less toxicity than when the entire
      prostate is dose escalated.

PMID- 29188193
TI  - The Use of Flow Cytometry in Myelodysplastic Syndromes: A Review.
AB  - Myelodysplastic syndromes (MDSs) are a heterogeneous group of hematopoietic stem
      cell diseases categorized by dysplasia in one or more hematopoietic cell
      lineages, as well as cytopenia and functional abnormalities in bone marrow cells.
      Several MDS classification methods have been proposed to categorize the disease
      and help professionals better plan in patients' treatment. The World Health
      Organization classification, released in 2008 and revised in 2016, is the
      currently and the most used classification method worldwide. Recent advances in
      MDS molecular biology and innovations in flow cytometry have enabled the
      development of new parameters for MDS diagnosis and classification. Several
      groups have published flow cytometry scores and guidelines useful for the
      diagnosis and/or prognosis of MDS, which are mostly based on detecting
      immunophenotypic abnormalities in granulocyte, monocyte, and lymphoid lineages.
      Here, we review the current literature and discuss the main parameters that
      should be analyzed by flow cytometry with the aim of refining MDS diagnosis and
      prognosis. Furthermore, we discuss the critical role of flow cytometry and
      molecular biology in MDS diagnosis and prognosis, as well as the current
      challenges and future perspectives involving these techniques.

PMID- 29188196
TI  - The treatment of low-grade septic non-unions.
AB  - Non-union (or pseudoarthrosis) is defined as a fracture that fails to consolidate
      after 6 months from the trauma. Current conservative treatments consist of
      biological (i.e. with calcium, Vitamin D) and mechanical stimulation. Moreover,
      surgical approaches include the use of endomidollar nail osteosynthesis,
      compression plates that are often associated with bone grafts. External fixation
      is a valid surgical alternative especially in case of septic non-unions. Indeed,
      compression-distraction osteosynthesis results in a significant improvement in
      bone vascularisation and exerts a powerful osteoinductive stimulus on the non
      union site. In this review, we will describe a cohort of patients affected by low
      grade septic non-unions and treated with external fixation.

PMID- 29188194
TI  - Beyond Paralogs: The Multiple Layers of Redundancy in Bacterial Pathogenesis.
AB  - Redundancy has been referred to as a state of no longer being needed or useful.
      Microbiologists often theorize that the only case of true redundancy in a haploid
      organism would be a recent gene duplication event, prior to divergence through
      selective pressure. However, a growing number of examples exist where an organism
      encodes two genes that appear to perform the same function. For example, many
      pathogens translocate multiple effector proteins into hosts. While disruption of
      individual effector genes does not result in a discernable phenotype, deleting
      genes in combination impairs pathogenesis: this has been described as redundancy.
      In many cases, this apparent redundancy could be due to limitations of laboratory
      models of pathogenesis that do not fully recapitulate the disease process.
      Alternatively, it is possible that the selective advantage achieved by this
      perceived redundancy is too subtle to be measured in the laboratory. Moreover,
      there are numerous possibilities for different types of redundancy. The most
      common and recognized form of redundancy is functional redundancy whereby two
      proteins have similar biochemical activities and substrate specificities allowing
      each one to compensate in the absence of the other. However, redundancy can also
      exist between seemingly unrelated proteins that manipulate the same or
      complementary host cell pathways. In this article, we outline 5 types of
      redundancy in pathogenesis: molecular, target, pathway, cellular process, and
      system redundancy that incorporate the biochemical activities, the host target
      specificities and the impact of effector function on the pathways and cellular
      process they modulate. For each type of redundancy, we provide examples from
      Legionella pathogenesis as this organism employs over 300 secreted virulence
      proteins and loss of individual proteins rarely impacts intracellular growth. We
      also discuss selective pressures that drive the maintenance of redundant
      mechanisms, the current methods used to resolve redundancy and features that
      distinguish between redundant and non-redundant virulence mechanisms.

PMID- 29188195
TI  - Comparative Genomic Analysis of Two Clonally Related Multidrug Resistant
      Mycobacterium tuberculosis by Single Molecule Real Time Sequencing.
AB  - Background: Multidrug-resistant tuberculosis (MDR-TB) is posing a major threat to
      global TB control. In this study, we focused on two consecutive MDR-TB isolated
      from the same patient before and after the initiation of anti-TB treatment. To
      better understand the genomic characteristics of MDR-TB, Single Molecule Real
      Time (SMRT) Sequencing and comparative genomic analyses was performed to identify
      mutations that contributed to the stepwise development of drug resistance and
      growth fitness in MDR-TB under in vivo challenge of anti-TB drugs. Result: Both
      pre-treatment and post-treatment strain demonstrated concordant phenotypic and
      genotypic susceptibility profiles toward rifampicin, pyrazinamide, streptomycin,
      fluoroquinolones, aminoglycosides, cycloserine, ethionamide, and para
      aminosalicylic acid. However, although both strains carried identical missense
      mutations at rpoB S531L, inhA C-15T, and embB M306V, MYCOTB Sensititre assay
      showed that the post-treatment strain had 16-, 8-, and 4-fold elevation in the
      minimum inhibitory concentrations (MICs) toward rifabutin, isoniazid, and
      ethambutol respectively. The results have indicated the presence of additional
      resistant-related mutations governing the stepwise development of MDR-TB. Further
      comparative genomic analyses have identified three additional polymorphisms
      between the clinical isolates. These include a single nucleotide deletion at
      nucleotide position 360 of rv0888 in pre-treatment strain, and a missense
      mutation at rv3303c (lpdA) V44I and a 6-bp inframe deletion at codon 67-68 in
      rv2071c (cobM) in the post-treatment strain. Multiple sequence alignment showed
      that these mutations were occurring at highly conserved regions among pathogenic
      mycobacteria. Using structural-based and sequence-based algorithms, we further
      predicted that the mutations potentially have deleterious effect on protein
      function. Conclusion: This is the first study that compared the full genomes of
      two clonally-related MDR-TB clinical isolates during the course of anti-TB
      treatment. Our work has demonstrated the robustness of SMRT Sequencing in
      identifying mutations among MDR-TB clinical isolates. Comparative genome analysis
      also suggested novel mutations at rv0888, lpdA, and cobM that might explain the
      difference in antibiotic resistance and growth pattern between the two MDR-TB
      strains.

PMID- 29188198
TI  - Evaluation of the changing landscape of prostate cancer diagnosis and management
      from 2005 to 2016.
AB  - Background: Approaches to prostate cancer (PCa) diagnosis and treatment have
      evolved significantly over past decades. There has been an increasing focus on
      minimizing overdiagnosis and overtreatment of clinically insignificant PCa. The
      objective of this study was to evaluate the changes in the diagnostic approach
      and initial treatment strategy that has evolved over time in an Australian
      urological private practice. Materials and methods: Men with newly diagnosed PCa
      were identified from the private practice electronic and paper medical records
      from 2005 to 2016 and data was consolidated into six groups of 2-year intervals.
      Diagnostic strategy was analyzed with particular reference to the use of
      multiparametric magnetic resonance imaging (mpMRI) scan and 68Ga-prostate
      specific membrane antigen (PSMA) positron emission tomography/computed tomography
      (PET/CT) scans. National Comprehensive Cancer Network risk group stratification
      was correlated with initial treatment strategy and compared over time. Results:
      Chart review identified 839 men who had a mean age of 65.8 years. In 2011-2012,
      prebiopsy mpMRI scan was introduced. Its uptake correlated with a decrease in
      numbers of men diagnosed with low risk cancer (r = -0.80, P = 0.04) and an
      increase in numbers of men diagnosed with high-risk cancer (r = 0.90, P = 0.01).
      The use of 68Ga-PSMA PET/CT was associated with decreasing use of CT and bone
      scans performed. Open radical prostatectomy had a declining trend particularly
      when robotic surgery (robotic assisted radical prostatectomy (RARP)) was
      introduced. Pelvic lymph node dissections performed progressively decreased. An
      increased use of luteinizing hormone receptor hormone (LHRH) antagonists was seen
      in favor of LHRH agonists. Whilst use of high dose rate brachytherapy declined,
      there was an increased use of low dose rate brachytherapy. Conclusion: Prebiopsy
      mpMRI has been associated with an increased proportion of newly diagnosed men
      having clinically significant PCa. Over time, 68Ga-PSMA PET/CT scans, robotic
      assisted radical prostatectomy (RARP) and LHRH antagonists have increased in use,
      whilst CT and bone scans, and pelvic lymph node dissections have decreased.

PMID- 29188199
TI  - Effects of 25- and 30-degree Trendelenburg positions on intraocular pressure
      changes during robot-assisted radical prostatectomy.
AB  - Background: The objective of this study was to assess the effects of 25-degree
      and 30-degree Trendelenburg positions on intraocular pressure (IOP) changes
      during robot-assisted radical prostatectomy (RARP). Materials and methods: This
      prospective study involved a total of 30 consecutive patients undergoing RARP.
      All participants were randomly divided into two groups: Trendelenburg position
      with the head down at 25 degrees or 30 degrees. In addition to representative
      operative outcomes, IOP was measured at six discrete time points; Time 1 (T1):
      before induction of general anesthesia, patients in a horizontal supine position;
      T2: after induction of general anesthesia, patients in a horizontal supine
      position; T3: 1 hour after adopting the Trendelenburg position; T4: 2 hours after
      adopting the Trendelenburg position; T5: after pneumoperitoneum resolution in the
      Trendelenburg position; T6: anesthetized before awakening in a supine position.
      Results: The total and console operative times, estimated blood loss, and
      intravenous fluid intake during RARP did not significantly differ between the two
      groups. While the IOP values measured at the same time points were similar
      between the two groups, the 25-degree Trendelenburg position significantly
      attenuated the IOP change from T1 to T3, T4, and T5 compared with those at 30
      degrees. Conclusions: These findings suggest that RARP in the 25-degree
      Trendelenburg position may reduce the risks of position-related ophthalmic
      complications without increasing the difficulty of the surgical procedure.

PMID- 29188197
TI  - 68Ga-prostate-specific membrane antigen-positron emission tomography/computed
      tomography in advanced prostate cancer: Current state and future trends.
AB  - The early and accurate detection of prostate cancer is important to ensure timely
      management and appropriate individualized treatment. Currently, conventional
      imaging has limitations particularly in the early detection of metastases and at
      prostate-specific antigen (PSA) levels < 2.0 ng/mL. Furthermore, disease
      management such as salvage radiotherapy is best at low PSA levels. Thus, it is
      critical to capture the disease in the oligometastatic stage as disease
      progression and commencement of systemic therapies can be delayed by metastasis
      directed therapy. Prostate-specific membrane antigen (PSMA) is overexpressed in
      prostatic cancer cells. Novel imaging modalities using radiolabeled tracers with
      PSMA such as 68Ga-PSMA-positron emission tomography (PET)/computed tomography
      (CT) have shown promising results. We review the literature regarding 68Ga-PSMA
      PET/CT in the setting of primary prostate cancer and biochemical recurrence. At
      present, the best utilization of 68Ga-PSMA-PET/CT appears to be in biochemical
      recurrence. 68Ga-PSMA-PET/CT has high diagnostic accuracy for lymph node
      metastases and has been shown to have superior detection rates to conventional
      imaging, especially at low PSA levels. The exact role of 68Ga-PSMA-PET/CT in
      primary prostate cancer is not yet entirely clear. It has an improved detection
      rate for smaller lesions and may be able to identify nodal or distant metastatic
      disease at an earlier stage. While still experimental, there may also be value in
      combining 68Ga-PSMA-PET to multiparametric magnetic resonance imaging for staging
      of intraprostatic disease. To date, 68Ga-PSMA-PET/CT has been shown to have
      considerable clinical value and to impact treatment selection for patients with
      prostate cancer. Still in its infancy, the results of future clinical trials will
      be excitedly awaited.

PMID- 29188200
TI  - Management and outcomes of Gleason six prostate cancer detected on needle biopsy:
      A single-surgeon experience over 6 years.
AB  - Objective: To assess the management and oncological outcomes in men diagnosed
      with Gleason score (GS) 6 prostate cancer on needle biopsy in a regional centre,
      as compared with published international data. Materials and methods: A
      retrospective analysis was conducted of patients who were diagnosed with GS 6
      prostate cancer via transrectal ultrasound-guided or transperineal biopsy between
      June 2009 and September 2015 under the care of a single surgeon. Data were
      obtained from a prospectively collected database. Results: A total of 166
      patients were diagnosed with GS 6 prostate cancer. The mean age was 61 (range 46
      79) years, with mean prostate-specific antigen of 6.7 (0.91-26.8) ng/mL at
      diagnosis. Of 166 patients, 117 (70.5%) patients were enrolled into the active
      surveillance program with 82 (70%) meeting Prostate Cancer Research International
      Active Surveillance (PRIAS) criteria, 44 patients underwent immediate definitive
      treatment (88.6% radical prostatectomy and 9.1% radiotherapy) and five watchful
      waiting. With a median follow-up of 1.8 years, 37 (31.6%) patients on AS had
      definitive treatment [30 cases (81%) were attributable to disease progression, 4
      cases (10.8%) to an abnormal magnetic resonance imaging result and 3 cases (8.1%)
      for patient preference]. In the 35 patients who underwent radical prostatectomy
      immediately after diagnosis, the GS was >=7 in 29 cases (82.9%), and the final
      pathology was pT3a in 16 (51.6%) and pT3b in one (2.9%). In patients who
      underwent radical prostatectomy after being on AS, the proportion of GS >=7
      prostate cancer was 29/32 (90.6%), with pT3a in six (18.8%) and pT3b in three
      (9.4%) cases. Overall, 23.5% of patients had a multiparametric magnetic resonance
      imaging scan. Conclusion: This single-surgeon cohort of GS 6 prostate cancer
      patients demonstrates a high proportion of cases managed with active
      surveillance, with comparable rates to international literature. The majority of
      cases who underwent immediate definitive treatment had significant disease,
      indicating that patients are being appropriately selected for active
      surveillance.

PMID- 29188202
TI  - Seminal plasma enables selection and monitoring of active surveillance candidates
      using nuclear magnetic resonance-based metabolomics: A preliminary investigation.
AB  - Background: Diagnosis and monitoring of localized prostate cancer requires
      discovery and validation of noninvasive biomarkers. Nuclear magnetic resonance
      (NMR)-based metabolomics of seminal plasma reportedly improves diagnostic
      accuracy, but requires validation in a high-risk clinical cohort. Materials and
      methods: Seminal plasma samples of 151 men being investigated for prostate cancer
      were analyzed with 1H-NMR spectroscopy. After adjustment for buffer (add-to
      subtract) and endogenous enzyme influence on metabolites, metabolite profiling
      was performed with multivariate statistical analysis (principal components
      analysis, partial least squares) and targeted quantitation. Results: Seminal
      plasma metabolites best predicted low- and intermediate-risk prostate cancer with
      differences observed between these groups and benign samples. Lipids/lipoproteins
      dominated spectra of high grade samples with less metabolite contributions.
      Overall prostate cancer prediction using previously described metabolites was not
      validated. Conclusion: Metabolomics of seminal plasma in vitro may assist
      urologists with diagnosis and monitoring of either low or intermediate grade
      prostate cancer. Less clinical benefit may be observed for high-risk patients.
      Further investigation in active surveillance cohorts, and/or in combination with
      in vivo magnetic resonance spectroscopic imaging may further optimize localized
      prostate cancer outcomes.

PMID- 29188201
TI  - Significant prognostic difference between Grade Group 4 and 5 in the 2014
      International Society of Urological Pathology Grading System for High Grade
      Prostate Cancer with Bone Metastasis.
AB  - Background: To investigate prognostic difference between Gleason Score (GS) 8 and
      9-10, as the 2014 International Society of Urological Pathology Gleason Grading
      Systems proposed, in patients with prostate cancer (PCa) with bone metastasis.
      Materials and methods: We retrospectively reviewed data on 106 patients with GS 8
      10 between 2006 and 2016. All patients received androgen deprivation therapy
      immediately. We validated biochemical recurrence, PCa-specific survival, and
      overall survival, and analyzed the predictive value for overall survival.
      Results: Patients with GS 9-10 had significantly lower PCa-specific survival
      (50.5% vs. 83.4%, P = 0.01) and overall survival (38.8% vs. 66.3%, P = 0.04) at 5
      years than those with GS 8, while biochemical recurrence rate was not
      significantly different (P = 0.26). Furthermore, these significant differences
      between GS 8 and 9-10 were also observed among high-risk groups proposed in Japan
      Cancer of the Prostate Risk Assessment Stratification (prostate cancer-specific
      survival: P = 0.03, overall survival: P = 0.04, respectively). Pathological GS 9
      10 was an independent prognostic factor for overall survival (hazard ratio =
      1.97, P = 0.04) in multivariable cox proportional hazard regression analysis.
      Among patients with GS 9-10, albumin level was an only prognostic factor for
      overall survival (hazard ratio = 0.33, P < 0.01). Conclusion: Pathological GS 9
      10 predicts significantly worse outcomes than GS 8 in Japanese PCa patients with
      bone metastasis. Our data indicated clinical significance of discriminating the
      2014 International Society of Urological Pathology Gleason Grading Group 4 and 5
      among high-risk PCa patients with bone metastasis.

PMID- 29188204
TI  - Greetings from the New Editor-in-Chief.

PMID- 29188203
TI  - Comparison of Visual Prostate Symptom Score and International Prostate Symptom
      Score in the evaluation of men with benign prostatic hyperplasia: A prospective
      study from an Indian population.
AB  - Background: Lower urinary tract symptoms (LUTSs) due to benign prostatic
      hyperplasia (BPH) are common conditions in middle-age or older men. The
      International Prostate Symptom Score (IPSS) is a useful and validated
      questionnaire to evaluate LUTS secondary to BPH. Van der Walt et al have
      developed an alternative questionnaire named the Visual Prostate Symptom Score
      (VPSS) questionnaire. This study aimed to evaluate the relationship between the
      VPSS and IPSS in the evaluation of men with LUTSs due to BPH in an Indian
      population. Materials and methods: This was a prospectively designed study
      conducted at Sri Sathya Sai Institute of Higher Medical Sciences, Prashanthigram
      (Anantapur, Andhra Pradesh, India). A total of 121 patients who presented to the
      urology outpatient department with LUTS due to BPH were enrolled in the study.
      Patients were followed up at 1-month and 3-month intervals. All patients were
      given both questionnaires. The correlation test was used to assess the
      correlation between two symptom scores and various parameters. Observations with
      a P value < 0.05 were considered statistically significant. Results: There was a
      statistically significant difference in the number of patients requiring
      assistance to fill the questionnaires according to their education level. There
      was a positive correlation between IPSS total score and VPSS total score (r =
      0.7235; P < 0.0001), VPSS total score and VPSS quality of life (Qol; r = 0.70753;
      p < 0.0001), IPSS total versus IPSS Qol (r = 0.65583; P < 0.0001), and IPSS Qol
      versus VPSS Qol (r = 0.84093; P < 0.0001). A negative correlation was observed
      between total VPSS with Qmax, total IPSS with Qmax, IPSS total versus Qavg (r = 
      0.479; P < 0.0001), and VPSS total versus Qavg (r = -0.5; P < 0.0001). All VPSS
      questions showed statistically significant correlation with the corresponding
      IPSS questions. Conclusion: There is a statistically significant correlation
      between the VPSS and IPSS and it can be completed by a greater number of patients
      without assistance.

PMID- 29188205
TI  - Recurred Intracranial Meningioma: A Retrospective Analysis for Treatment Outcome
      and Prognostic Factor.
AB  - Background: In this study, we aimed to compare repeated resection and radiation
      treatment, such as Gamma knife radiosurgery (GKRS) or conventional radiotherapy
      (RT), and investigate the factors influencing treatment outcome, including
      overall survival (OS), progression-free survival (PFS), and complication rates.
      Methods: We retrospectively reviewed 67 cases of recurred intracranial
      meningiomas (repeated resection: 36 cases, radiation treatment: 31 cases) with 56
      months of the median follow-up duration (range, 13-294 months). Results: The
      incidence of death rate was 29.9% over follow-up period after treatment for
      recurred meningiomas (20/67). As independent predictable factors for OS, benign
      pathology [hazard ratio (HR) 0.132, 95% confidence interval (CI) 0.048-0.362,
      p<0.001] and tumor size <3 cm (HR 0.167, 95% CI 0.061-0.452, p<0.001) were
      significantly associated with a longer OS. The incidence of progression rate was
      23.9% (16/67). Only treatment modality was important for PFS as an independent
      predictable factor (GKRS/RT vs. open resection; HR 0.117, 95% CI 0.027-0.518,
      p<0.005). The complication rate was 14.9% in our study (10/67). Larger tumor size
      (>=3 cm, HR 0.060, 95% CI 0.007-0.509, p=0.010) was significant as an independent
      prognostic factor for development of complications. Although treatment modality
      was not included for multivariate analysis, it should be considered as a
      predictable factor for complications (p=0.001 in univariate analysis).
      Conclusion: The role of repeated resection is questionable for recurred
      intracranial meningiomas, considering high progression and complication rates.
      Frequent and regular imaging follow-up is required to detect recurred tumor sized
      as small as possible, and radiation treatment can be a preferred treatment.

PMID- 29188207
TI  - Ependymomas: Prognostic Factors and Outcome Analysis in a Retrospective Series of
      33 Patients.
AB  - Background: The purpose of this study was to evaluate the prognostic factors and
      outcomes in patients with ependymoma to management plans. Methods: Between 1997
      and 2013, 33 patients with 25 ependymomas (WHO grade II) and eight anaplastic
      ependymomas (WHO grade III) were pathologically diagnosed. Six were pediatric
      patients (mean age, 6.15 years; range, 1.3-11 years), while 27 were adults (mean
      age, 47.5 years; range, 19-70 years). Of those, there were 12 adult patients with
      totally resected ependymomas without anaplastic pathology and adjuvant treatment.
      Prognostic factors were assessed in ependymoma patients. Prognostic factors were
      studied using Kaplan-Meier estimates in subgroups. Results: For six pediatric
      patients, the progression-free survival (PFS) was 43.7+/-13.5 months, and the
      overall survival (OS) was 58.1+/-13.7 months. For 27 adult patients, the PFS was
      125.6+/-14.3 months, and the OS was 151.2+/-12.5 months. Age demonstrated a
      statistically significant effect on PFS (p=0.03) and OS (p=0.03). In adult
      ependymomas, the extent of tumor removal significantly affected PFS (p=0.03) and
      trended towards an effect on OS (p=0.06). Out of 12 patients with totally
      resected ependymomas without anaplastic pathology and adjuvant treatment, one
      patient showed tumor recurrence during follow-up (mean, 93.5 months; range, 27.9
      162.7 months). Conclusion: Adult patients with ependymomas were found to have
      better survival rates compared to pediatric patients. We suggest that totally
      resected adult ependymomas without anaplastic pathology could be observed without
      any adjuvant treatment, regardless of the tumor location.

PMID- 29188208
TI  - The Clinical Outcome of Hydroxyurea Chemotherapy after Incomplete Resection of
      Atypical Meningiomas.
AB  - Background: The aim of this study is to investigate the clinical results of
      adjuvant chemotherapy with hydroxyurea and to compare those with the results of
      postoperative radiotherapy after incomplete resection of atypical meningiomas
      (ATMNGs). Methods: We retrospectively reviewed the medical records of 84 patients
      with ATMNGs diagnosed in the period from January 2000 to December 2014. Clinical
      data included patient sex and age at the time of surgery, presenting symptoms at
      diagnosis, location and size of tumor, extent of surgery, use of postoperative
      radiotherapy or hydroxyurea chemotherapy, duration of follow-up, and progression.
      In terms of the extent of surgical resection, incomplete resection was defined as
      Simpson grade II-V. Results: Among the 85 patients, 55 (65.5%) patients underwent
      incomplete resection; 24 (43.6%) were treated with adjuvant hydroxyurea (group
      A), and 20 (36.4%) with postoperative radiotherapy (group B), and 11 (20.0%)
      underwent conservative treatment after surgery (group C). Twenty-five (45.5%)
      patients experienced the progression of tumors during the follow-up period (mean
      47.7 months, range 12.4-132.1 months); 8 of 24 (33.3%) patients in group A, 7 of
      20 (35.0%) patients in group B, and 10 of 11 (90.9%) patients in group C. The
      mean progression-free survival (PFS) was 30.9 months (range 6.4-62.3 months);
      46.2 months in group A, 40.4 months in group B, and 11.9 months in group C
      (p=0.041). Multivariate analysis showed that Simpson grade (p=0.040), adjuvant
      treatment after surgery (p<0.001), increased Ki67 (p=0.017), mitotic index
      (p=0.034), and overexpression of p53 (p=0.026) predicted longer PFS. Conclusion:
      This investigation suggested that adjuvant treatment after incomplete resection
      of ATMNGs are associated with longer PFS than conservative treatment, and that
      there is no difference of PFS between hydroxyurea chemotherapy and radiotherapy
      after surgery. Therefore, hydroxyurea chemotherapy can be considered as another
      adjuvant tool for the ATMNGs if the postoperative adjuvant radiotherapy cannot be
      applicable.

PMID- 29188209
TI  - Outcomes in 20 Gynecologic Cancer Patient with Brain Metastasis: A Single
      Institution Retrospective Study.
AB  - Background: The incidence of brain metastasis (BM) in gynecologic cancers has
      risen recently, due to prolonged survival times and an early diagnosis. We
      analyzed treatment outcomes of patients with BM from gynecologic cancers.
      Methods: Among 951 patients with BM who were treated in neurosurgical department
      from July 2003 to February 2016, a total of 20 (2%) patients were from
      gynecologic cancers. The patients' clinical characteristics were collected by
      using medical records. There were 14 (66.7%) ovarian cancers, 4 (19.0%) uterine
      cancers, and 2 (9.5%) cervical cancers. As a primary treatment modality, 11
      patients were treated with Gamma Knife surgery (GKS), 6 with surgical resection
      followed by whole brain radiation therapy (WBRT), and 3 with WBRT only. Overall
      and progression-free survival according to the primary origin and the primary
      treatment were analyzed. Results: Median overall survival time was 28 months, and
      progression-free survival was 15 months. In patients with ovarian cancer, median
      overall survival did not reach during the follow-up periods and progression-free
      survival time was 15 months. Median overall survival time in patients who
      received GKS as the primary treatment was 17 months and that in patients who
      underwent surgical resection followed by WBRT was 37.3 months (p=0.16). The
      median value of progression-free survival time in patients who received GKS as
      the primary treatment was 12 months and that in patients who underwent surgical
      resection with WBRT was 42 months (p=0.042). Median follow up period of over all
      patients was 13 months. Conclusion: BM from gynecologic cancer is rare (2%), but
      our findings suggest that the prognosis might not always be poor. In our small
      series, surgical resection with WBRT was a treatment modality significantly
      associated with a longer progression-free survival. Additional studies with more
      cases and multi-institutional cooperation are needed to determine which treatment
      modality leads to better outcomes.

PMID- 29188206
TI  - Genomic and Molecular Characterization of Brain Tumors in Asian and Non-Asian
      Patients of Los Angeles: A Single Institution Analysis.
AB  - Background: Worldwide, approximately 2% of new cancers are of the brain. Five
      year survival rates among brain cancer patients have been reported as a little
      over a third. Differences in clinical outcomes between brain tumor patients of
      different races remain poorly understood. Methods: A retrospective chart review
      was performed on brain tumor resection patients>=18 years old. Demographics,
      treatment variables, and survival outcomes were collected. Primary outcomes were
      length of stay, recurrence rate, progression-free survival (PFS), and overall
      survival (OS). Results: A total of 452 patients were included in analysis.
      Females and males had nearly a 1:1 ratio (n=242 and n=220, respectively). Mean
      age was 54.8 years (SD: 14.5 range: 18-90). Females composed 69% (n=48) of Asian
      patients; males constituted 31% (n=22). Mean age of the Asian patients was 55.9
      years (SD: 14.6 range: 26-89). Asian-only cohort tumor pathologies included
      glioblastoma (GBM) (n=14), high-grade glioma (n=7), low-grade glioma (n=4),
      meningioma (n=38), and metastases (n=7). Of the 185 meningioma patients, non
      Asian patients comprised 79% of the group (n=146). Of the 65 GBM patients in
      total, non-Asian patients made up 89% of the GBM cohort (n=58). There were no
      statistically significant differences between these groups of both cohorts in
      recurrence (p=0.1580 and p=0.6294, respectively), PFS (p=0.9662 and p=0.4048,
      respectively), or OS (p=0.3711 and p=0.8183, respectively). Conclusion: Studies
      evaluating the survival between patients of different racial backgrounds against
      several tumor varieties are rare. Patients of certain racial backgrounds may need
      additional consideration when being attended to despite the same mutational
      composition as their counterparts. Repeated studies using national databases may
      yield more conclusive results.

PMID- 29188210
TI  - Pituitary Ependymoma, 10-Year Follow-Up after Partial Resection and Radiation
      Therapy.
AB  - Ependymoma usually arises within the ventricles and central canal of the spinal
      cord. These tumors, found in the sellar region, are extremely rare. We report a
      case of pituitary ependymoma followed up over 10 years. A 59-year-old male
      patient presented with fatigue, general weakness, erectile dysfunction, and loss
      of body hair, including pubic hair. Brain magnetic resonance imaging (MRI)
      revealed a 3.3*3.5*2.3-cm sellar and suprasellar snowman-shaped enhancing mass.
      The tumor was partially resected via the trans-sphenoidal approach followed by
      postoperative radiation therapy. The pathologic confirmation was pituitary
      ependymoma. At the 10-year follow up, MRI revealed no evidence of tumor
      progression. With lack of knowledge about pituitary ependymoma, our case is the
      only case in which the disease has been well controlled over a long period of
      time without tumor progression.

PMID- 29188211
TI  - Response of Leptomeningeal Dissemination of Anaplastic Glioma to Temozolomide:
      Experience of Two Cases.
AB  - The incidence of leptomeningeal dissemination (LMD) of anaplastic glioma has been
      increasing. LMD can be observed at the time of initial presentation or the time
      of recurrence. As a result of both rarity and unusual presentation, a standard
      therapy has not yet been suggested. In contrast to leptomeningeal carcinomatosis
      for systemic solid cancers, a relatively prolonged survival is observed in some
      patients with LMD of anaplastic gliomas. Treatment modalities include whole
      craniospinal irradiation, intra-cerebrospinal fluid (CSF) chemotherapy, and
      systemic chemotherapy. In some cases, response to temozolomide (TMZ), with or
      without combined radiation has been reported. Here, we report two cases of LMD of
      an anaplastic glioma. In one case LMD presented at the time of diagnosis, and in
      the other at the time of recurrence after radiation. CSF cytology was positive in
      both cases, and persisted in spite of intrathecal methotrexate chemotherapy.
      Later, TMZ was prescribed for progressing brain parenchymal lesions, and both
      radiological and cytological responses were obtained after oral TMZ treatment.

PMID- 29188212
TI  - Supratentorial Pilocytic Astrocytoma Mimicking Convexity Meningioma with Early
      Anaplastic Transformation: A Case Report.
AB  - Meningiomas and pilocytic astrocytomas are benign intracranial tumors. Pilocytic
      astrocytomas arises frequently at the posterior fossa in childhood. Meningiomas
      have several image findings, such as a dural tail sign, bony erosion, and
      sunburst appearance on angiography. However, pilocytic astrocytomas with these
      findings have been rarely reported. In this report, we describe a mass with
      typical image findings of a meningioma, but diagnosed as a supratentorial
      pilocytic astrocytoma with early anaplastic transformation.

PMID- 29188213
TI  - Pituicytoma with Significant Tumor Vascularity Mimicking Pituitary Macroadenoma.
AB  - A 19-year-old man presented with bitemporal hemianopsia and was found to have a
      large sellar and suprasellar tumor, resembling a pituitary macroadenoma.
      Emergency transsphenoidal approach was attempted because of rapid visual
      deterioration with headache. However, the approach was complicated and stopped by
      uncontrolled hemorrhage from the tumor. After conventional cerebral angiography
      and recognition of an unusual pathology, transcranial approach was achieved to
      prevent permanent visual loss. The final pathological diagnosis was pituicytoma
      with epithelioid features. Pituicytoma is a rare low-grade tumor (WHO Grade I) of
      pituicytes involving the sellar and suprasellar region, and originating from
      special glial cells of the neurohypophysis. Because of the high vascularity, the
      firm consistency, and invasion to surrounding neurovascular structures, a
      pituicytoma should be included in the differential diagnosis of a mass in the
      sellar and suprasellar area if the tumor shows high enhancement with vascular
      components. We report a case of rare pituicytoma mimicking a pituitary
      macroadenoma with massive hemorrhage to disturb surgery.

PMID- 29188214
TI  - Subfrontal Schwannoma Extended Broadly to Nasal Cavity Treated by Gamma Knife
      Radiosurgery Following Surgical Excision: A Case Report.
AB  - Subfrontal schwannomas are rarely reported. They are usually found only in the
      subfrontal area, but some extend to the nasal cavity. In these cases, prevention
      of postoperative cerebrospinal fluid (CSF) leakage through thinned or eroded
      anterior skull base is important. A 51-year-old female with anosmia and mild
      nausea was diagnosed as subfrontal extraaxial mass with nasal cavity extension.
      This mass was initially thought to be an olfactory groove meningioma. We
      performed a bifrontal craniotomy for surgical excision. We did not totally remove
      the tumor, as we wanted to prevent a skull base defect. The histopathological
      diagnosis was a schwannoma. There was no postoperative complication such as CSF
      leakage. The residual tumor was treated with gamma knife radiosurgery. The nasal
      cavity mass has not grown as of five years after radiosurgery.

PMID- 29188216
TI  - Extra-Axial and Clear Cell Type Ependymoma, Mimicking a Convexity Meningioma.
AB  - A 33-year-old woman presented with tingling and paresthesia on left extremity for
      2 months. Magnetic resonance imaging revealed that the tumor was iso- and hypo
      intensity on T1-weighted image, mixed iso- and high-signal intensity on T2
      weighted images and heterogeneously enhanced with rim enhancement. Neither
      arachnoid cleft nor dural tail was certain but mass was located extra-axially so
      meningioma was suspected. During operation, tumor wasn't attached to dura at all
      but arachnoid attachment was seen. Pathologically, clear cell type ependymoma was
      confirmed. Details of diagnosis and treatment of this tumor is described.

PMID- 29188215
TI  - Astroblastoma in a Young Female Patient: A Case Report and Literature Review of
      Clinicopathological, Radiological and Prognostic Characteristics and Current
      Treatment Strategies.
AB  - Astroblastoma is an uncommon glial tumor with predominant manifestation in the
      young age. Herein, we report a case of 18-year-old astroblastoma female patient
      who presented with history of two months headache. Magnetic resonance imaging
      (MRI) of the brain demonstrated well circumscribed, intra-axial abnormal signal
      intensity lesion (size=5*4 cm2) in the right parieto-occipital region of the
      brain. The patient underwent complete surgical resection of the gross tumor, as
      confirmed by an early post-surgical MRI (i.e., within 24 hours of surgery).
      Histopathological examination revealed neoplastic lesion exhibiting perivascular
      pseudo-rosettes with centrally hyalinized blood vessel and focal nuclear
      pleomorphism. Immunohistochemistry staining illustrated reactivity for glial
      fibrillary acidic protein and integrase interactor 1 (INI-1). These features
      rendered the diagnosis of astroblastoma. A comprehensive review of the current
      literature to summarize the clinicopathological and radiological characteristics,
      prognostic factors and current treatment strategies of astroblastomas is also
      presented. Our study would expand the pool of this uncommon tumor towards its
      better understanding and optimal treatment.

PMID- 29188217
TI  - Prediction of the Thermal Conductivity of Refrigerants by Computational Methods
      and Artificial Neural Network.
AB  - Background: The thermal conductivity of fluids can be calculated by several
      computational methods. However, these methods are reliable only at the confined
      levels of density, and there is no specific computational method for calculating
      thermal conductivity in the wide ranges of density. Methods: In this paper, two
      methods, an Artificial Neural Network (ANN) approach and a computational method
      established upon the Rainwater-Friend theory, were used to predict the value of
      thermal conductivity in all ranges of density. The thermal conductivity of six
      refrigerants, R12, R14, R32, R115, R143, and R152 was predicted by these methods
      and the effectiveness of models was specified and compared. Results: The results
      show that the computational method is a usable method for predicting thermal
      conductivity at low levels of density. However, the efficiency of this model is
      considerably reduced in the mid-range of density. It means that this model cannot
      be used at density levels which are higher than 6. On the other hand, the ANN
      approach is a reliable method for thermal conductivity prediction in all ranges
      of density. The best accuracy of ANN is achieved when the number of units is
      increased in the hidden layer. Conclusion: The results of the computational
      method indicate that the regular dependence between thermal conductivity and
      density at higher densities is eliminated. It can develop a nonlinear problem.
      Therefore, analytical approaches are not able to predict thermal conductivity in
      wide ranges of density. Instead, a nonlinear approach such as, ANN is a valuable
      method for this purpose.

PMID- 29188218
TI  - Neuropsychological Correlates of Pre-Frailty in Neurocognitive Disorders: A
      Possible Role for Metacognitive Dysfunction and Mood Changes.
AB  - Background: Recent studies have suggested that cognitive functions in patients
      with neurocognitive disorders have a significant role in the pathogenic
      mechanisms of frailty. Although pre-frailty is considered an intermediate,
      preclinical state, epidemiological research has begun to dislodge cognition and
      frailty into their specific subcomponents to understand the relationship among
      them. We aim to analyse the possible association between pre-frailty and
      neuropsychological variables to outline which factors can contribute to minor and
      major neurocognitive disorders. Methods: 60 subjects complaining of different
      cognitive deficits underwent a deep-in-wide frailty and neuropsychological
      assessment. We conducted three multiple linear regression analyses adjusted for a
      combination of demographic measures and involving several neuropsychological
      behavioural parameters selected by the literature on physical frailty. Results:
      We found a significant association between frailty-as measured by the
      multidimensional prognostic index (MPI)-and action monitoring and monetary gain
      (cognitive domain), depression and disinhibition (behavioural domain). Moreover,
      an association between MPI and impaired awareness for instrumental activities
      disabilities exists. Conclusion: We propose a novel framework for understanding
      frailty associated with metacognitive-executive dysfunction.

PMID- 29188220
TI  - Evaluation of measurement tools for tobacco product displays: is there an app for
      that?
AB  - Tobacco product displays are a pervasive presence in convenience stores,
      supermarkets, pharmacies, and other retailers nationwide. The influence that
      tobacco product displays have on purchases and tobacco product initiation,
      particularly on young people and other vulnerable populations, is well known. An
      objective measurement tool that is valid, reliable, and feasible to use is needed
      to assess product displays in the retail setting. This study reports on the
      relative accuracy of various tools that measure area and/or distance in photos
      and thus could be applied to product displays. We compare results of repeated
      trials using five tools. Three tools are smartphone apps that measure objects in
      photos taken on the device; these are narrowed down from a list of 284 candidate
      apps. Another tool uses photos taken with any device and calculates relative area
      via a built-in function in the Microsoft Office Suite. The fifth uses photos
      taken with the Narrative Clip, a "life-logging" wearable camera. To evaluate
      validity and reliability, we assess each instrument's measurements and calculate
      intra-class correlation coefficients. Mean differences between observed
      measurements (via tape measure) and those from the five tools range from just
      over one square foot to just over two square feet. Most instruments produce
      reliable estimates though some are sensitive to the size of the display. Results
      of this study indicate need for future research to test innovative measurement
      tools. This paper also solicits further discussion on how best to transform
      anecdotal knowledge of product displays as targeted and disproportionate
      marketing tactics into a scientific evidence base for public policy change.

PMID- 29188221
TI  - The influence of political candidates' facial appearance on older and younger
      adults' voting choices and actual electoral success.
AB  - Younger adults (YA) judgments of political candidates' competence from facial
      appearance accurately predict electoral success. Whether this is true for older
      adults (OA) has not been investigated despite the fact that OA are more likely to
      vote than YA and may respond differently to particular facial qualities. We
      examined whether OA and YA ratings of competence, trustworthiness,
      attractiveness, and babyfaceness of opposing candidates in US Senate elections
      independently predicted their own vote choices and actual election outcomes. OA
      and YA ratings of attractiveness, competence, and trustworthiness positively
      predicted their choices, but the effect of competence was weaker for OA.
      Babyfaceness negatively predicted OA, but not YA, choices. OA and YA competence
      ratings equally predicted the actual election winners, while OA, but not YA,
      attractiveness ratings did so. Trustworthy and babyface ratings did not predict
      actual winners. These findings have implications for understanding age
      differences in candidate preferences and the prediction of election outcomes.

PMID- 29188219
TI  - A Systematic Review of the Role of Robotics in Plastic and Reconstructive Surgery
      From Inception to the Future.
AB  - Background: The use of robots in surgery has become commonplace in many
      specialties. In this systematic review, we report on the current uses of robotics
      in plastic and reconstructive surgery and looks to future roles for robotics in
      this arena. Methods: A systematic literature search of Medline, EMBASE, and
      Scopus was performed using appropriate search terms in order to identify all
      applications of robot-assistance in plastic and reconstructive surgery. All
      articles were reviewed by two authors and a qualitative synthesis performed of
      those articles that met the inclusion criteria. The systematic review and results
      were conducted and reported in accordance with the Preferred Reporting Items for
      Systematic Reviews and Meta Analysis (PRISMA) guidelines. Results: A total of
      7,904 articles were identified for title and abstract review. Sixty-eight studies
      met the inclusion criteria. Robotic assistance in plastic and reconstructive
      surgery is still in its infancy, with areas such as trans-oral robotic surgery
      and microvascular procedures the dominant areas of interest currently. A number
      of benefits have been shown over conventional open surgery, such as improved
      access and greater dexterity; however, these must be balanced against
      disadvantages such as the lack of haptic feedback and cost implications.
      Conclusion: The feasibility of robotic plastic surgery has been demonstrated in
      several specific indications. As technology, knowledge, and skills in this area
      improve, these techniques have the potential to contribute positively to patient
      and provider experience and outcomes.

PMID- 29188223
TI  - Dataset on the cost estimation for spent filter backwash water (SFBW) treatment.
AB  - The dataset presented in this article are related to the research article
      entitled "Hybrid coagulation-UF processes for spent filter backwash water
      treatment: a comparison studies for PAFCl and FeCl3 as a pre-treatment" (Ebrahimi
      et al., 2017) [1]. This article reports the cost estimation for treating produced
      spent filter backwash water (SFBW) during water treatment in Isfahan- Iran by
      various methods including primary sedimentation, coagulation & flocculation,
      second clarification, ultra filtration (UF) and recirculation of settled SFBW to
      water treatment plant (WTP) entrance. Coagulation conducted by PAFCl and FeCl3 as
      pre polymerized and traditional coagulants. Cost estimation showed that contrary
      to expectations, the recirculation of settled SFBW to WTP entrance is more
      expensive than other method and it costs about $ 37,814,817.6. Versus the
      cheapest option related to separate primary sedimentation, coagulation &
      flocculation in WTP. This option cost about $ 4,757,200 and $ 950,213 when FeCl3
      and PAFCl used as coagulant, respectively.

PMID- 29188222
TI  - Effects of 3-year denosumab treatment on hip structure in Japanese postmenopausal
      women and men with osteoporosis.
AB  - Denosumab, a human monoclonal antibody against RANK ligand, is shown to have
      strong anti-fracture effects in Japanese osteoporosis patients. However, there
      have been no data showing actions on Japanese bone architecture. Here we show
      that denosumab continuously improves several geometrical parameters calculated by
      hip structural analysis for 3 years. Compared to placebo, denosumab significantly
      increased bone mineral density, cortical thickness and cross sectional area in
      all of the three analyzed areas: the narrow neck, intertrochanter and femoral
      shaft. The subsequent derived mechanical parameters, cross-sectional moment of
      inertia, section modulus and buckling ratio, were also improved by denosumab. In
      addition, the improvement of these parameters was also observed in the patients
      that had switched from placebo to denosumab treatment. The present study suggests
      the structural evidence explaining the strong anti-fracture efficacy of denosumab
      and its significant effects on cortical bone in Japanese.

PMID- 29188224
TI  - Data on partial polyhydroxyalkanoate synthase genes (phaC) mined from Aaptos
      aaptos marine sponge-associated bacteria metagenome.
AB  - We report data associated with the identification of three polyhydroxyalkanoate
      synthase genes (phaC) isolated from the marine bacteria metagenome of Aaptos
      aaptos marine sponge in the waters of Bidong Island, Terengganu, Malaysia. Our
      data describe the extraction of bacterial metagenome from sponge tissue,
      measurement of purity and concentration of extracted metagenome, polymerase chain
      reaction (PCR)-mediated amplification using degenerate primers targeting Class I
      and II phaC genes, sequencing at First BASE Laboratories Sdn Bhd, and
      phylogenetic analysis of identified and known phaC genes. The partial nucleotide
      sequences were aligned, refined, compared with the Basic Local Alignment Search
      Tool (BLAST) databases, and released online in GenBank. The data include the
      identified partial putative phaC and their GenBank accession numbers, which are
      Rhodocista sp. phaC (MF457754), Pseudomonas sp. phaC (MF437016), and an
      uncultured bacterium AR5-9d_16 phaC (MF457753).

PMID- 29188225
TI  - Data from the analytical performance of the Abaxis Piccolo Xpress point of care
      analyzer in whole blood, serum, and plasma.
AB  - The objective of this study was to examine the analytical performance of 14
      comprehensive metabolic panel analytes on the Abaxis Piccolo Xpress(r) Point of
      Care analyzer in serum, plasma, and whole blood. A method comparison was
      performed on all three specimen types intended for use on the Piccolo Xpress(r):
      serum, heparinized plasma, and whole blood. This data is also presented in Murata
      et al. (2015) [1]. This article includes the actual Bland-Altman bias plots of
      the difference in results obtained for analytes in the comprehensive metabolic
      panel from the Abaxis Piccolo Xpress and the comparison instrument, the Ortho
      Vitros.

PMID- 29188226
TI  - Data on RNA-seq analysis of Garcinia mangostana L. seed development.
AB  - Mangosteen (Garcinia mangostana L.) has exceptional potential for commercial and
      pharmaceutical applications due to its delicious fruit and medicinal properties.
      Nevertheless, the molecular mechanism of mangosteen seed development is poorly
      understood. In this study, we performed transcriptomic analysis of four seed
      developmental stages; eight, ten, twelve and fourteen weeks after anthesis.
      Illumina HiSeqTM 4000 sequencer was used to generate raw data of approximately 68
      Gb in size. From 451,495,326 raw reads, 406,143,756 clean reads were obtained.
      The raw data were uploaded to SRA database and the BioProject ID is PRJNA395504.
      These data provide the basis for further exploration and understanding of the
      molecular mechanism in mangosteen seed development.

PMID- 29188227
TI  - A corpus and a concordancer of academic journal articles.
AB  - This data article presents a corpus (i.e. a selection of a big number of words in
      an electronic form) and a concordancer (i.e. a tool to show the word in its
      context of use) of academic journal articles. As the title suggests, the data
      were collected from research articles published in academic journals. The corpus
      contains 5,686,428 words selected from 895 journal articles published by Elsevier
      in 2011-2015. The corpus is classified into four subject areas: Health sciences,
      Life sciences, Physical Sciences, and Social Sciences, following the
      classifications of Scopus, which is the largest abstract and citation database of
      peer-reviewed scientific journals, books and conference proceedings. To ease the
      access and utilization of the corpus, a program to produce the key word in
      context (KWIC) and word frequency was created and placed on the website:
      corpus.kwary.net. The corpus is a valuable resource for researchers, teachers,
      and translators working on academic English.

PMID- 29188228
TI  - Implicit Theory of Mind - An overview of current replications and non
      replications.
AB  - The current dataset contains a qualitative summary of (non-)replication studies
      of implicit Theory of Mind paradigms. It summarizes for each paradigm, how many
      replications, partial replications and non-replications were identified and how
      many of them were published or unpublished. Furthermore, descriptive data and
      sample sizes are reported. The dataset provides a qualitative overview of the
      published and unpublished findings in implicit Theory of Mind research.

PMID- 29188229
TI  - Data on internal cDNA amplification and color changes of the proteins derived
      from Pacific white leg shrimp shell.
AB  - In this article, we report original data on the designation of the primers for
      full-length cDNA amplification and the internal cDNA amplification of red color
      related pigment-binding protein derived from shrimp shell. Data on the color
      shifts of different soluble proteins under 100  degrees C 10 min heat treatment
      and the effects of heating temperatures (from 30 to 100  degrees C) on the color
      changes of crude water-soluble proteins are also included in this report. For
      further details and experimental findings please refer to the article "Isolation
      and cDNA cloning of a novel red color-related pigment-binding protein derived
      from the shell of shrimp, Litopenaeus vannamei" (Chuang et al., 2017) [1].

PMID- 29188230
TI  - Primers and copper responsive promoter design and data of real-time RT-PCR assay
      in filamentous fungus Trichoderma reesei.
AB  - This data article contains data related to the research article entitled "Copper
      mediated on-off control of gene expression in filamentous fungus Trichoderma
      reesei" (Wang et al., 2017) [1]. Four kinds of copper responsive promoters were
      designed. Quantitative PCR (qPCR) was performed to determine relative mRNA levels
      of red fluorescent protein gene (rfp) extracted from cells grown under different
      concentrations of CuSO4. Three deletion vectors were constructed by using a
      copper-mediated self-excision cassette instead of a xylose-mediated self-excision
      cassette (Zhang et al., 2016) [2] to knock out xyn1, one of the two major
      specific endo-beta-1,4-xylanases (Rauscher et al., 2006) [3], xyr1, the key
      transcriptional activator of cellulolytic and xylanolytic genes (Lichius et al.,
      2015) [4], and ace3, a factor essential for cellulase production (Hakkinen et
      al., 2014) [5]. This data article reports the primers, vector construction, and
      qPCR assay.

PMID- 29188231
TI  - Forward and reverse mapping for milling process using artificial neural networks.
AB  - The data set presented is related to the milling process of AA6061-4.5%Cu-5%SiCp
      composite. The data primarily concentrates on predicting values of some machining
      responses, such as cutting force, surface finish and power utilization utilizing
      using forward back propagation neural network based approach, i.e. ANN based on
      three process parameters, such as spindle speed, feed rate and depth of cut.The
      comparing reverse model is likewise created to prescribe the ideal settings of
      processing parameters for accomplishing the desired responses as indicated by the
      necessities of the end clients. These modelling approaches are very proficient to
      foresee the benefits of machining responses and also process parameter settings
      in light of the experimental technique.

PMID- 29188233
TI  - The effects of scoliosis and subsequent surgery on the shape of the torso.
AB  - Background: Adolescent idiopathic scoliosis (AIS) causes asymmetry of the torso,
      and this is often the primary concern of patients. Surgery aims to minimise the
      visual asymmetry. It is not clear how scoliosis makes the torso asymmetric or how
      scoliosis surgery changes that asymmetry when compared to the distribution of
      asymmetries seen in a non-scoliotic group of normal controls. Methods: Surface
      topography images were captured for a group with AIS both pre-operatively and
      post-operatively. Identifiable points were compared between the images to
      identify the effects of AIS on the shape of the torso by looking at the relative
      heights and distances from the midline of the shoulders, axillae and waist in a
      two-dimensional coronal view. This was then compared to a previously reported
      group of normal non-scoliotic children to analyse whether surgery recreated
      normality. Results: There were 172 pairs of images with 164 females and 8 males,
      mean age at pre-operative scan of 13.7 years. The normal group was 642 images
      (237 females and 405 males) from 116 males and 79 females, mean age of 12.5
      years.The curve patterns seen in the scoliotic group matched the patterns of a
      main thoracic curve (n = 146) and main thoracolumbar curve (n = 26). The
      asymmetries seen in both shoulders, axillae and waist were different between the
      two different types of curve. Across both groups, the shoulder asymmetry was less
      than that of the corresponding axillae.There was a statistically significant
      reduction in all asymmetries following surgery in the main thoracic group (p <
      0.001). This was not seen in the main thoracolumbar group, thought to be due to
      the small sample size. In the main thoracic group, there were statistically
      significant differences in the asymmetries between the post-operative and normal
      groups in the shoulders and axillae (p < 0.001) but not the waist. Conclusions:
      This paper demonstrates quantitatively the range of asymmetries seen in the AIS
      torso and the degree to which surgery alters them. Surgery does not recreate
      normality but does cause a statistically significant change in torso shape
      towards that seen in a non-scoliotic group.

PMID- 29188232
TI  - Colorectal Cancer Cells Adhere to and Migrate Along the Neurons of the Enteric
      Nervous System.
AB  - Background & Aims: In several types of cancers, tumor cells invade adjacent
      tissues by migrating along the resident nerves of the tumor microenvironment.
      This process, called perineural invasion, typically occurs along extrinsic
      nerves, with Schwann cells providing physical guidance for the tumor cells.
      However, in the colorectal cancer microenvironment, the most abundant nervous
      structures belong to the nonmyelinated intrinsic enteric nervous system (ENS). In
      this study, we investigated whether colon cancer cells interact with the ENS.
      Methods: Tumor epithelial cells (TECs) from human primary colon adenocarcinomas
      and cell lines were cocultured with primary cultures of ENS and cultures of human
      ENS plexus explants. By combining confocal and atomic force microscopy, as well
      as video microscopy, we assessed tumor cell adhesion and migration on the ENS. We
      identified the adhesion proteins involved using a proteomics approach based on
      biotin/streptavidin interaction, and their implication was confirmed further
      using selective blocking antibodies. Results: TEC adhered preferentially and with
      stronger adhesion forces to enteric nervous structures than to mesenchymal cells.
      TEC adhesion to ENS involved direct interactions with enteric neurons. Enteric
      neuron removal from ENS cultures led to a significant decrease in tumor cell
      adhesion. TECs migrated significantly longer and further when adherent on ENS
      compared with on mesenchymal cells, and their trajectory faithfully followed ENS
      structures. Blocking N-cadherin and L1CAM decreased TEC migration along ENS
      structures. Conclusions: Our data show that the enteric neuronal network guides
      tumor cell migration, partly via L1CAM and N-cadherin. These results open a new
      avenue of research on the underlying mechanisms and consequences of perineural
      invasion in colorectal cancer.

PMID- 29188234
TI  - Radiolabeled cholesteryl ethers: A need to analyze for biological stability
      before use.
AB  - Radiolabeled cholesteryl ethers are widely used as non-metabolizable tracers for
      lipoproteins and lipid emulsions in a variety of in vitro and in vivo
      experiments. Since cholesteryl ethers do not leave cells after uptake and are not
      hydrolyzed by mammalian cellular enzymes, these compounds can act as markers for
      cumulative cell uptakes of labeled particles. We have employed [3H]cholesteryl
      oleoyl ether to study the uptake and distribution of triglyceride-rich emulsion
      particles on animal models. However, questionable unexpected results compelled us
      to analyze the stability of these ethers. We tested the stability of two
      commercially available radiolabeled cholesteryl ethers - [3H]cholesteryl oleoyl
      ether and [3H]cholesteryl hexadecyl ether from different suppliers, employing in
      vitro, in vivo and chemical model systems. Our results show that, among the two
      cholesteryl ethers tested, one ether was hydrolyzed to free cholesterol in vitro,
      in vivo and chemically under alkaline hydrolyzing agent. Free cholesterol, unlike
      cholesteryl ether, can then re-enter the circulation leading to confounding
      results. The other ether was not hydrolyzed to free cholesterol and remained as a
      stable ether. Hence, radiolabeled cholesteryl ethers should be analyzed for
      biological stability before utilizing them for in vitro or in vivo experiments.

PMID- 29188235
TI  - Precise dating of the Middle-to-Upper Paleolithic transition in Murcia (Spain)
      supports late Neandertal persistence in Iberia.
AB  - The late persistence in Southern Iberia of a Neandertal-associated Middle
      Paleolithic is supported by the archeological stratigraphy and the radiocarbon
      and luminescence dating of three newly excavated localities in the Mula basin of
      Murcia (Spain). At Cueva Anton, Mousterian layer I-k can be no more than 37,100
      years-old. At La Boja, the basal Aurignacian can be no less than 36,500 years
      old. The regional Middle-to-Upper Paleolithic transition process is thereby
      bounded to the first half of the 37th millennium Before Present, in agreement
      with evidence from Andalusia, Gibraltar and Portugal. This chronology represents
      a lag of minimally 3000 years with the rest of Europe, where that transition and
      the associated process of Neandertal/modern human admixture took place between
      40,000 and 42,000 years ago. The lag implies the presence of an effective barrier
      to migration and diffusion across the Ebro river depression, which, based on
      available paleoenvironmental indicators, would at that time have represented a
      major biogeographical divide. In addition, (a) the Phlegraean Fields caldera
      explosion, which occurred 39,850 years ago, would have stalled the
      Neandertal/modern human admixture front because of the population sink it
      generated in Central and Eastern Europe, and (b) the long period of ameliorated
      climate that came soon after (Greenland Interstadial 8, during which forests
      underwent a marked expansion in Iberian regions south of 40 degrees N) would have
      enhanced the "Ebro Frontier" effect. These findings have two broader
      paleoanthropological implications: firstly, that, below the Ebro, the
      archeological record made prior to 37,000 years ago must be attributed, in all
      its aspects and components, to the Neandertals (or their ancestors); secondly,
      that modern human emergence is best seen as an uneven, punctuated process during
      which long-lasting barriers to gene flow and cultural diffusion could have
      existed across rather short distances, with attendant consequences for ancient
      genetics and models of human population history.

PMID- 29188236
TI  - Novel Dominant-Negative GH Receptor Mutations Expands the Spectrum of GHI and IGF
      I Deficiency.
AB  - Context: Autosomal-recessive mutations in the growth hormone receptor (GHR) are
      the most common causes for primary growth hormone insensitivity (GHI) syndrome
      with classical GHI phenotypically characterized by severe short stature and
      marked insulin-like growth factor (IGF)-I deficiency. We report three families
      with dominant-negative heterozygous mutations in the intracellular domain of the
      GHR causing a nonclassical GHI phenotype. Objective: To determine if the
      identified GHR heterozygous variants exert potential dominant-negative effects
      and are the cause for the GHI phenotype in our patients. Results: All three
      mutations (c.964dupG, c.920_921insTCTCAAAGATTACA, and c.945+2T>C) are predicted
      to result in frameshift and early protein termination. In vitro functional
      analysis of variants c.964dupG and c.920_921insTCTCAAAGATTACA (c.920_921ins14)
      suggests that these variants are expressed as truncated proteins and, when
      coexpressed with wild-type GHR, mimicking the heterozygous state in our patients,
      exert dominant-negative effects. Additionally, we provide evidence that a
      combination therapy of recombinant human growth hormone (rhGH) and rhIGF-I
      improved linear growth to within normal range for one of our previously reported
      patients with a characterized, dominant-negative GHR (c.899dupC) mutation.
      Conclusion: Dominant-negative GHR mutations are causal of the mild GHI with
      substantial growth failure observed in our patients. Heterozygous defects in the
      intracellular domain of GHR should, therefore, be considered in cases of
      idiopathic short stature and IGF-I deficiency. Combination therapy of rhGH and
      rhIGF-I improved growth in one of our patients.

PMID- 29188237
TI  - Fewer Circulating Natural Killer Cells 28 Days After Double Cord Blood
      Transplantation Predicts Inferior Survival and IL-15 Response.
AB  - Natural Killer (NK) cell immune reconstitution after double umbilical cord blood
      transplantation (dUCBT) is rapid and thought to be involved in graft vs. leukemia
      (GvL) reactions. To investigate the role of NK cell recovery on clinical
      outcomes, the absolute number of NK cells at Day 28 after dUCBT was determined
      and patients with low numbers of NK cells had inferior two year disease-free
      survival (hazard ratio 1.96; p=0.04). A detailed developmental and functional
      analysis of the recovering NK cells was performed to link NK recovery and patient
      survival. The proportion of NK cells in each developmental stage was similar for
      patients with low, medium, and high Day 28 NK cell numbers. As compared to
      healthy controls, patients post-transplant showed reduced NK functional responses
      upon K562 challenge (CD107a, IFN-gamma, and TNFalpha); however, there were no
      differences based on Day 28 NK cell number. Patients with low NK numbers had 30%
      less STAT5 phosphorylation in response to exogenous IL-15 (p=0.04) and decreased
      Eomes expression (p=0.025) compared to patients with high NK numbers. Decreased
      STAT5 phosphorylation and Eomes expression may be indicative of reduced
      sensitivity to IL-15 in the low NK cell group. Incubation of patient samples with
      IL-15 superagonist (ALT803) increased cytotoxicity and cytokine production in all
      patient groups. Thus, clinical interventions, including administration of IL-15
      early after transplantation may increase NK cell number and function and, in
      turn, improve transplantation outcomes.

PMID- 29188238
TI  - Depot medroxyprogesterone acetate administration alters immune markers for HIV
      preference and increases susceptibility of peripheral CD4+ T cells to HIV
      infection.
AB  - Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an
      increased risk of HIV acquisition. In a longitudinal study, we investigated the
      impact of Depo-Provera use by healthy women on expression of immune markers for
      HIV preference and on HIV infection ex vivo at baseline (visit 1), one month
      (visit 2) and three months (visit 3) after Depo-Provera treatment. We found a
      significant increase in the frequency and expression of integrin alpha4beta7 on
      CD4+ T cells at visit 2. Interestingly, Hispanic but not black women exhibited a
      significant increase in integrin alpha4beta7 cell numbers and expression levels
      at visit 2, whereas, black but not Hispanic women exhibited a significant change
      in CCR5 and CD38 expression levels between visit 2 and visit 3. The frequency of
      terminal effector memory CD4+ T cells decreased significantly in black women from
      visit 1 to visit 3. Virus production following ex vivo HIV infection of PBMCs was
      increased at visit 3 compared to visit 1. In black women, the frequency of HIV
      p24+CD4+ T cells was higher at visit 3 than at visit 1. Expression of integrin
      alpha4beta7 on HIV p24+CD4+ T cells following ex vivo infection at visit 2 was
      significantly less than at visit 1. These results demonstrate that Depo-Provera
      alters the immune profile of peripheral CD4+ T cells and increases susceptibility
      to HIV infection ex vivo. The observation that these effects differed between
      women of different ethnicities has implications for developing effective and
      targeted strategies for HIV prevention.

PMID- 29188239
TI  - A graphene oxide nanosensor enables the co-delivery of aptamer and peptide probes
      for fluorescence imaging of a cascade reaction in apoptotic signaling.
AB  - Cytochrome c (Cyt c) and caspase-3 are the key mediators in apoptotic signaling.
      As is known to all, the release of Cyt c from mitochondria is a vital caspase
      activation pathway and defines the point of no-return in cell apoptosis. However,
      it has not been reported that any fluorescence imaging tools could allow
      simultaneous visualization of Cyt c translocation and caspase-3 activation in
      apoptotic cells. Here, we develop a sensitive nanosensor that holds the
      capability of imaging of the released Cyt c from the mitochondria and a caspase-3
      activation cascade reaction in apoptotic signaling. The nanosensor is constructed
      by the assembly of a fluorophore (Cy5)-tagged DNA aptamer on graphene nanosheets
      that have been covalently immobilized with a FAM-labeled peptide. After a
      spatially selective delivery into the cytoplasm, the Cy5-tagged DNA aptamer
      assembled on the nanosensor can bind with Cyt c released from the mitochondria to
      the cytoplasm and dissociate from graphene, triggering a red fluorescence signal.
      In addition, the caspase-3 activated by the Cyt c released to the cytoplasm can
      cleave the FAM-labeled peptide and result in a green fluorescence output. The
      nanosensor exhibits rapid response, high sensitivity and selectivity for in vitro
      assays, and high contrast imaging of Cyt c and caspase-3 in living cells. It also
      provides the method for the study of the kinetic relationship between the Cyt c
      translocation and caspase-3 activation through simultaneous imaging of Cyt c and
      caspase-3. The developed nanosensor described here will be an efficient and
      potential platform for apoptosis research.

PMID- 29188240
TI  - SPIONs for cell labelling and tracking using MRI: magnetite or maghemite?
AB  - Although there is extensive literature covering the biomedical applications of
      superparamagnetic iron oxide nanoparticles (SPIONs), the phase of the iron oxide
      core used is not often taken into account when cell labelling and tracking
      studies for regenerative medicine are considered. Here, we use a co-precipitation
      reaction to synthesise particles of both magnetite- (Fe3O4) and maghemite- (gamma
      Fe2O3) based cores and consider whether the extra synthesis step to make
      maghemite based particles is advantageous for cell tracking.

PMID- 29188241
TI  - Microscopic understanding of the conformational features of a protein-DNA
      complex.
AB  - Protein-DNA interactions play crucial roles in different biological processes.
      Binding of a protein to its target DNA is the key step at different stages of
      genetic activities. In this article, we have carried out atomistic molecular
      dynamics simulations to understand the microscopic conformational and dynamical
      features of the N-terminal domain of the lambda-repressor protein and its
      operator DNA in their complexed state. The calculations revealed that the overall
      flexibility of the protein and the DNA components reduces due to complex
      formation. In particular, increased ordering of the DNA sugar rings bound to the
      protein is found to be associated with modified ring puckering. Attempts have
      been made to study the effect of complexation on the internal motions of the
      protein and the DNA components. It is demonstrated that the non-uniform ordering
      of the side chains of lysine residues in the consensus sequence leads to
      differential behavior of the two monomers of the homodimeric protein.

PMID- 29188242
TI  - Highly transparent and rollable PVA-co-PE nanofibers synergistically reinforced
      with epoxy film for flexible electronic devices.
AB  - The development of electronics towards a more functions-integrated, flexible and
      stretchable direction requires mechanically flexible substrates with high thermal
      and dimensional stability and optical transparency. Herein, rolls of an optically
      transparent PVA-co-PE nanofibrous membrane/epoxy composite with synergistically
      enhanced thermal stability, very low CTE, and outstanding mechanical properties
      are reported. The nanoscale size, the unique inter-stack structure, and the
      strong interfacial interactions between the PVA-co-PE nanofibers and the epoxy
      contribute to the synergistic effects. Because of the match between the
      refractive index (RI) of the PVA-co-PE nanofibers and the epoxy matrix, the
      visible light transmittance of nanocomposite film could be as high as 85% and the
      composite film was still optically transparent with a nanofiber loading content
      of up to 61.7 wt%. The break strength and compliance matrix of the composite film
      with a high fiber loading of 61.7 wt% increased by 2.3 times of that of the neat
      epoxy film and exceeded 3000 m2 N-1, respectively. PVA-co-PE nanofibers have a
      very low CTE value (3.634 * 10-6 K-1) and could be applicable as a reinforcement
      to reduce the thermal expansion of epoxy. Furthermore, we developed a flexible
      alternating current electroluminescent (ACEL) device based on the transparent
      composite film and the experimental results showed that the transparent composite
      film could serve as substrate for flexible electronic devices. In addition, their
      electrical and optical properties were evaluated.

PMID- 29188243
TI  - Cellular traction forces: a useful parameter in cancer research.
AB  - The search for new cancer biomarkers is essential for fundamental research,
      diagnostics, as well as for patient treatment and monitoring. Whereas most cancer
      biomarkers are biomolecules, an increasing number of studies show that mechanical
      cues are promising biomarker candidates. Although cell deformability has been
      shown to be a possible cancer biomarker, cellular forces as cancer biomarkers
      have been left largely unexplored. Here, we measure traction forces of cancer and
      normal-like cells at high spatial resolution using a robust method based on dense
      vertical arrays of nanowires. A force map is created using automated image
      analysis based on the localization of the fluorescent tips of the nanowires. We
      show that the force distribution and magnitude differ between MCF7 breast cancer
      cells and MCF10A normal-like breast epithelial cells, and that monitoring
      traction forces can be used to investigate the effects of anticancer drugs.

PMID- 29188244
TI  - Nitrilium ions - synthesis and applications.
AB  - Nitrilium ions have been well-established in organic chemistry for many decades,
      but recent developments show them to be far more versatile than hitherto
      recognized. They are known as stable salts, can be generated in situ, or are
      present as transient intermediates. We provide a succinct, but comprehensive
      review on the synthesis, stability, and reactivity of nitrilium ions as synthons
      for imines, their use in the synthesis of a large spectrum of heterocycles, and
      their reactions with transition metal complexes. By offering this overview, we
      aim for a renewed focus on readily accessible and simple to use nitrilium ions as
      valuable reagents for the synthesis of organic compounds.

PMID- 29188245
TI  - A microfluidic chip capable of generating and trapping emulsion droplets for
      digital loop-mediated isothermal amplification analysis.
AB  - Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification
      technique that rapidly amplifies specific DNA molecules at high yield. In this
      study, a microfluidic droplet array chip was designed to execute the digital LAMP
      process. The novel device was capable of 1) creating emulsion droplets, 2)
      sorting them into a 30 * 8 droplet array, and 3) executing LAMP across the 240
      trapped and separated droplets (with a volume of 0.22 nL) after only 40 min of
      reaction at 56  degrees C. Nucleic acids were accurately quantified across a
      dynamic range of 50 to 2.5 * 103 DNA copies per MUL, and the limit of detection
      was a single DNA molecule. This is the first time that an arrayed emulsion
      droplet microfluidic device has been used for digital LAMP analysis. When
      compared to microwell digital nucleic acid amplification assays, this droplet
      array-based digital LAMP assay eliminates the constraint on the size of the
      digitized target, which was determined by the dimension of the microwells for its
      counterparts. Moreover, the capacity for hydrodynamic droplet trapping allows the
      chip to operate in a one-droplet-to-one-trap manner. This microfluidic chip may
      therefore become a promising device for digital LAMP-based diagnostics in the
      near future.

PMID- 29188246
TI  - Fast and scalable synthesis of uniform zirconium-, hafnium-based metal-organic
      framework nanocrystals.
AB  - Metal-organic frameworks based on zirconium or hafnium possess tantalizing
      commercial prospects due to their high stability but require a long reaction time
      to form crystals. The fast synthesis of uniform Zr-, Hf-MOF nanocrystals at scale
      is of key importance in the potential commercial application of MOFs. In this
      work, we have developed a versatile strategy through controlling the hydrolysis
      and nucleation of metal salts in the presence of acetic acid and water; up to 24
      grams of UiO-66-NH2 nanocrystals with a uniform octahedron could be synthesized
      within 15 minutes using a one step method. The current synthetic strategy could
      be extended to other Zr-, Hf-MOF nanocrystals [UiO-66-Fast, UiO-66-(OH)2-Fast,
      UiO-66-2,6-NDC-Fast, UiO-67-Fast, BUT-12-Fast, PCN-222-Ni-Fast, PCN-222-Co-Fast,
      Hf-UiO-66-Fast, Hf-UiO-66-NH2-Fast, Hf-UiO-66-(OH)2-Fast, Hf-UiO-66-2,6-NDC-Fast
      and Hf-BUT-12-Fast]. Significantly, when noble metal nanoparticles (NPs) are
      introduced into MOF precursors, NPs encapsulated in MOFs with excellent
      dispersion have also been obtained and show outstanding performance in catalysis.
      This facile procedure is expected to pave the way to expand the commercial
      applications of MOFs.

PMID- 29188247
TI  - High quality and high performance adsorption of Congo red using as-grown MWCNTs
      synthesized over a Co-MOF as a catalyst precursor via the CVD method.
AB  - A Co(ii) metal-organic framework (MOF) based on the pyridyl-amide-carboxylate-3
      (2-pyridinecarboxylic acid)amido pyridine (HPCAP) ligand, namely [Co(PCAP)2].2H2O
      (1), has been hydrothermally synthesized and structurally characterized, which
      was firstly used as a combined catalyst precursor to synthesize multi-walled
      carbon nanotubes (MWCNTs). The decomposition of ethylene in the presence of the
      Co-MOF by the chemical vapor deposition (CVD) method at 800  degrees C led to
      successful production of high quality as-grown MWCNT products. Interestingly, the
      as-grown MWCNTs exhibit high performance in the selective adsorption of Congo red
      (CR) with an adsorption capacity of 1639 mg g-1.

PMID- 29188248
TI  - Pd-Catalyzed one-pot sequential cross-coupling reactions of tetrabromothiophene.
AB  - Unsymmetrical one-pot sequential cross-coupling reactions of sterically hindered
      tetrabromothiophene with arylboronic acid and an alkyne/alkene to afford
      selective bi-, tri-, and tetrasubstituted aryl/alkynyl-thiophenes with the aid of
      a palladium catalyst were described. The reaction proceeds via a site-selective
      Suzuki/Sonogashira coupling, followed by selective Sonogashira, Suzuki and Heck
      coupling reactions. This methodology has demonstrated an important framework for
      the synthesis of organic scaffolds.

PMID- 29188249
TI  - Accessing multimetallic complexes with a phosphorus(i) zwitterion.
AB  - We present the synthesis of a zwitterionic triphosphenium molecule,
      tBu(C5H2)(PPh2)2PI (L), which can act as a single- or multidentate ligand with
      group 6, 7, 8 and 9 metal carbonyl complexes. Group 6, [M(CO)5L] complexes are
      formed under photolytic conditions, where the metal is bound at the P(i) center.
      In the case of Mo(CO)6, the bimetallic complex [M(CO)5LMo(CO)3] is generated,
      which features bonds to both the phosphorus(i) center and the cyclopentadienyl
      moiety of the molecule. Interestingly, group 7 and 9 metal carbonyl dimers
      generate bimetallic complexes in the form [M2(CO)nL], where both metal centers
      are bound at the phosphorus(i) center. A detailed analysis of these molecules is
      provided, including X-ray diffraction, multinuclear NMR, infrared spectroscopy
      and computational investigations.

PMID- 29188250
TI  - Honeycomb-patterned hybrid films of surfactant-encapsulated polyoxometalates by a
      breath figure method and its electrocatalysis for BrO3.
AB  - In this paper, a sandwich type of polyoxophosphotungstate
      K7Na3[Cu4(H2O)2(PW9O34)2].20H2O (abbr. Cu4(PW9)2) was selected as an active unit
      to construct inorganic/organic hybrid materials. The ordered honeycomb structure
      of the surfactant-encapsulated polyoxometalate (SEP) complex was successfully
      obtained by using a famous breath figure method. Cu4(PW9)2 maintains typical
      features as confirmed by IR spectra, magnetization hysteresis studies and UV-vis
      spectra. An investigation of the effects of the relative humidity on the
      morphology of the honeycomb structures demonstrated a wide generality and high
      reproducibility of the formation of self-organized honeycomb-patterned films. In
      the present experiment, this magnetically ordered honeycomb was successfully
      deposited on indium tin oxide (ITO) substrates by directly casting the SEP
      chloroform solution. The cyclic voltammetric responses showed the redox couples
      of Cu4(PW9)2. The electrochemical behavior of the electrode was studied. In
      addition, the modified electrode exhibited high electrocatalytic activity for the
      reduction of BrO3-, which offered a new POM-based film material for the
      electrochemical fields.

PMID- 29188251
TI  - PNacPNacE: (E = Ga, In, Tl) - monomeric group 13 metal(i) heterocycles stabilized
      by a sterically demanding bis(iminophosphoranyl)methanide.
AB  - The salt metathesis reaction of the sterically demanding
      bis(iminophosphoranyl)methanide alkali metal complexes LM (L- = HC(Ph2P[double
      bond, length as m-dash]NDip)2-, Dip = 2,6-iPr2C6H3; M = Li, Na, K) with "GaI",
      InBr or TlBr afforded the monomeric group 13 metal(i) complexes LE:, E = Ga (1),
      In (2) and Tl (3) in moderate yields, and small quantities of LGaI24 in the case
      of Ga, respectively. The molecular structures of LE: 1-3 from X-ray single
      crystal diffraction show them to contain puckered six-membered rings with N,N'
      chelating methanide ligands and two-coordinated metal(i) centres. Reduction
      reactions of LAlI25, prepared by iodination of LAlMe2, were not successful and no
      aluminium(i) congener could be prepared so far. DFT studies on LE:, E = Al-Tl,
      were carried out and support the formulation as an anionic, N,N'-chelating
      methanide ligand coordinating to group 13 metal(i) cations. The HOMOs of the
      molecules for E = Al-In show a dominant contribution from a metal-based lone pair
      that is high in s-character.

PMID- 29188252
TI  - Real-time detection of oxalyl chloride based on a long-lived iridium(iii) probe.
AB  - A series of luminescent iridium(iii) complexes were designed and evaluated for
      their ability to detect oxalyl chloride ((COCl)2) at ambient temperature. In the
      presence of (COCl)2, a double amidation reaction takes place at the diamino
      functionality of complex 1, leading to the switching-on of a long-lived red
      luminescence with a 9-fold enhanced emission. Complex 1 exhibited high
      sensitivity and selectivity, with a detection limit for (COCl)2 at 32 nM.
      Additionally, complex 1 can be used to detect (COCl)2 using a simple smartphone,
      allowing for the portable and real-time monitoring of (COCl)2.

PMID- 29188253
TI  - Vibrational relaxation dynamics of beta-carotene and its derivatives with
      substituents on terminal rings in electronically excited states as studied by
      femtosecond time-resolved stimulated Raman spectroscopy in the near-IR region.
AB  - The electronic and vibrational relaxation of carotenoids is one of the key
      processes in the protection of living cells as well as in the functions of
      proteins involved in photosynthesis. In this study, the electronic and
      vibrational relaxation dynamics of beta-carotene and its derivatives with
      substituents on the terminal rings is investigated using femtosecond time
      resolved absorption and stimulated Raman spectroscopy in the near-IR region. The
      carbonyl substituent induces low-frequency shifts of the steady-state and
      transient absorption bands, decreases of the excited-state lifetimes and the
      acceleration of vibrational relaxation of the conjugated main chain, whereas the
      hydroxyl substituent only slightly affects them. The effects of the carbonyl
      group in the electronic relaxation dynamics are explained well by the lengthening
      of effective conjugation by the carbonyl group through a partial conjugation
      between the main chain and the terminal ring. Time-resolved near-IR stimulated
      Raman spectroscopy demonstrates the significance of the peripheral substitution
      with the carbonyl group for the vibrational energy relaxation of beta-carotene
      derivatives in the lowest excited singlet state.

PMID- 29188254
TI  - BODIPY dyes with thienyl- and dithienylthio-substituents - synthesis, redox and
      fluorescent properties.
AB  - 8-Phenyl- and 8-(4-nitrophenyl)-BODIPYs with thien-2-ylthio- and (2,2'-dithien-5
      yl)-thio-substitution at the 3,5-positions were synthesized. 2-Thienylthio
      derivatives were obtained using two different sequences, i.e., via nucleophilic
      substitution in the corresponding 1,9-dichlorodipyrromethenes, followed by BODIPY
      formation and via the same reaction using 3,5-dichloro-BODIPY dyes. The
      "dipyrromethene route" was observed to result in better overall yields. All the
      dyes were characterized by UV-Vis and fluorescence spectroscopy as well as cyclic
      voltammetry (CVA) studies. The UV-Vis spectra exhibited slight dependence on the
      thiophene chain length. The thienylthio derivatives fluoresce with modest quantum
      yields; conversely, no fluorescence has been detected for their dithienylthio
      counterparts. 8-Phenyl-3,5-di(thien-2-ylthio)-BODIPY was characterized by X-ray
      crystallography, which showed the layered arrangement of the molecules. The
      thienyl fragments of different molecules in the same layer form pairs alike H
      aggregates, whereas the BODIPYs moieties in the different layers are arranged in
      a J-aggregate fashion. Solid fluorescence was observed for these crystals with a
      broad emission from 600 nm to longer than 850 nm. The CVA results correspond to
      those for known substituted BODIPYs except for the unusually high current
      observed for the oxidation process of the dithienyl derivatives with respect to
      the reduction process. This finding indicates oxidative film deposition.

PMID- 29188255
TI  - Electrogenerated chemiluminescence of Ru(bpy)32+ at a black phosphorus quantum
      dot modified electrode and its sensing application.
AB  - Black phosphorus quantum dots (BPQDs) with an average size of 8.2 nm were
      synthesized through a liquid exfoliation method. The surface morphology and the
      thickness of the BPQDs were identified by high-resolution transmission microscopy
      (HRTEM), atomic force microscopy (AFM), and Raman spectroscopy. The
      electrogenerated chemiluminescence (ECL) behavior of Ru(bpy)32+ was investigated
      at a BPQD modified glassy carbon electrode under neutral conditions. A strong
      anodic ECL signal was obtained at the modified electrode in the absence of a
      coreactant, which is nearly three orders of magnitude larger than that at the
      bare electrode. Electrochemical results revealed that the oxidation process of
      Ru(bpy)32+ can be significantly catalyzed by BPQDs, suggesting that BPQDs can act
      as the coreactant of Ru(bpy)32+ to generate strong light emission. Dopamine could
      react with the oxidation product of Ru(bpy)32+ and exhibited an apparent
      inhibiting effect on ECL emission. As a result, it can be sensitively detected in
      the range of 0.1 nM to 50 nM with a detection limit of 0.022 nM. The present work
      revealed that BPQDs are a potential ECL platform, and which are promising in the
      fabrication of a novel ECL biosensor.

PMID- 29188256
TI  - How the hydrogen sorption properties of palladium are modified through
      interaction with iridium.
AB  - Hydrogen sorption (adsorption/absorption) in metals, in the form of thin films or
      nanoparticles, is a key process in the fields of energy storage and heterogeneous
      catalysis. Atomic hydrogen dissolved in the subsurface of a metal affects its
      surface atomic and electronic structures, and thereby its surface reactivity and
      catalytic properties. In addition, alloy effects modify both catalytic and
      hydrogen sorption phenomena. In order to rationalize recent experimental results
      showing the negative impact of hydrogen absorption on catalysis, the present
      article proposes an insight into structure-reactivity relationships through
      computational simulations, using density functional theory, of hydrogen sorption
      in the near-surface region of palladium atomic layers interacting with an iridium
      substrate. A detailed analysis of the electronic structure using local projected
      densities of states (PDOS) and crystal orbital overlap population (COOP) curves
      was carried out. It is found that the Pd/Ir system, with respect to pure Pd
      surfaces, keeps acceptable adsorption properties for surface reactions while
      preventing hydrogen penetration. The results of electronic structure calculations
      show that the most important difference between Pd and Ir is related to the
      strong anti-bonding character of the 1s-H/5p-Ir interaction, leading to the non
      bonding character of the sp-Ir interaction with hydrogen. Thus, increasing the Ir
      concentration in a Pd-based system increases the anti-bonding contribution, which
      strongly weakens the overall metal-hydrogen interaction.

PMID- 29188257
TI  - Microwave-assisted routes for rapid and efficient modification of layered
      perovskites.
AB  - Recent advances in exploiting microwave radiation in the topochemical
      modification of layered oxide perovskites are presented. Such methods work well
      for rapid bulk synthetic steps used in the production of novel inorganic-organic
      hybrids (protonation, grafting, intercalation, and in situ click reactions),
      exfoliation to produce dispersed nanosheets, and post-exfoliation processing to
      rapidly vary nanosheet surface groups. Compared to traditional methods that often
      take days, microwave methods can produce quality products in as little as 1-2 h.

PMID- 29188258
TI  - Filament dynamics in confined chemical gardens and in filiform corrosion.
AB  - Two reaction systems that are at first sight very different produce similar
      macroscopic filamentary product trails. The systems are chemical gardens confined
      to a Hele-Shaw cell and corroding metal plates that undergo filiform corrosion.
      We show that the two systems are in fact very much alike. Our experiments and
      analysis show that filament dynamics obey similar scaling laws in both instances:
      filament motion is nearly ballistic and fully self-avoiding, which creates self
      trapping events.

PMID- 29188259
TI  - High rate capability performance of ordered mesoporous TiNb6O17 microsphere
      anodes for lithium ion batteries.
AB  - We report the synthesis and application of ordered mesoporous TiNb6O17
      microspheres (M-TNO) using a one-step solvothermal method for the first time in
      lithium-ion batteries. The diameters of TiNb6O17 microspheres are in the range
      from 2.2 to 2.4 MUm with a mesopore size of about 35 nm, which promotes the
      electron and ion migration in charge/discharge processes. M-TNO shows a high
      specific capacitance (307.2 mA h g-1) at a low current density of 0.2 C and a
      long-term cycle life over 500 cycles as an electrode. The retentive capacity of
      the batteries is 77% of the initial cycle after 500 cycles. It is worth noting
      that M-TNO exhibits excellent rate capacity, which decreases slowly from 265.7 to
      172.4 mA h g-1 with the current density increasing from 1 C to 30 C. The
      retentive capacity at a current density of 30 C is 65% compared to that at 1 C.

PMID- 29188260
TI  - NO disproportionation by a {RhNO}9 pincer-type complex.
AB  - The reactivity of the {RhNO}9 complex [Rh(PCPtBu)(NO)] (1) with NO was studied. A
      disproportionation reaction takes place in which N2O is released quantitatively,
      while the complex Rh(PCPtBu)(NO)(NO2) (2), with coordinated nitrite, is formed.
      The new complex 2 was fully characterized by multinuclear NMR techniques, IR and
      X-ray diffraction. The X-ray structure reveals a square pyramidal geometry with
      an N-bound nitro ligand trans to the Cipso of the PCP ligand and a bent nitrosyl
      ligand in the apical position. IR measurement of released N2O confirms that one
      equivalent forms for each molecule of 1. Infrared spectroscopic experiments with
      1-15NO and 14NO suggest that the reaction occurs through the intermediacy of a
      dinitrosyl complex. In addition, DFT calculations were performed to provide more
      evidence on the structure of the intermediates and to support the observed
      reactivity.

PMID- 29188261
TI  - Nanoseed-assisted synthesis of nano-sized SAPO-34 zeolites using morpholine as
      the sole template with superior MTO performance.
AB  - Nano-sized SAPO-34 catalysts have been for the first time prepared using
      morpholine as the sole template by using a one-pot nanoseed-assisted method. The
      obtained nano-sized SAPO-34 catalysts exhibit about 4-fold prolonged lifetime and
      nearly 5% increased selectivity for ethylene and propylene compared to
      conventional micron-sized counterparts in methanol-to-olefin reactions.

PMID- 29188262
TI  - A chemoselective cleavable fluorescence turn-ON linker for proteomic studies.
AB  - We have developed a trifunctional cleavable fluorescence turn-ON linker for
      chemoproteomic applications. This novel linker, which became highly fluorescent
      only upon cleavage of the azo bond, was successfully used for in situ proteome
      profiling/target identification and studies on newly synthesised proteomes.

PMID- 29188263
TI  - On the calculation of multiplet energies of three-open-shell 4f135fn6d1 electron
      configuration by LFDFT: modeling the optical spectra of 4f core-electron
      excitation in actinide compounds.
AB  - Methodological concepts are reported for the calculation, without empirical
      parameters, of multiplet energy levels and ligand-field effects associated with
      three-open-shell 4f135fn6d1 electron configurations, and for the modeling of X
      ray absorption spectra in relation to intra-atomic 5fn -> 4f135fn6d1 electron
      transitions. A density functional theory (DFT) method is used for the
      determination of the electronic structure. An effective ligand-field Hamiltonian
      is also used to incorporate many body effects and corrections via the
      configuration interaction algorithm within the active space of Kohn-Sham orbitals
      with dominant actinide 4f, 5f and 6d characters. The theoretical method ensures a
      parameter-free ligand-field model, which will be implemented in the Amsterdam
      density functional (ADF) program package as part of the available and automated
      ligand-field density functional theory (LFDFT) routine. The theoretical method is
      illustrated with examples for applications: U4+ in the free ion and U4+ in bulk
      UO2 by means of the molecular (UO8)12- cluster. The DFT calculations are
      performed at different levels of the DFT functional, from which the LFDFT
      parameters such as Slater-Condon integrals, spin-orbit coupling constants and
      ligand-field potential (represented within the Wybourne formalism) are emulated.
      The comparison with available experimental data is good. Therefore, a non
      empirical ligand-field treatment of the 4f135fn6d1 configuration is established
      illustrating the spectroscopic details of the 4f core-electron excitation, which
      can be valuable for further understanding and prediction of the spectral profiles
      of actinide N6,7-edge X-ray absorption spectroscopy.

PMID- 29188264
TI  - Stabilization of hybrid perovskite CH3NH3PbI3 thin films by graphene passivation.
AB  - We report the long-term stability of water-sensitive hybrid perovskites
      CH3NH3PbI3 that were protected with monolayer graphene. This successful
      passivation was enabled by our development of a new water-free and polymer-free
      graphene transfer method. Monolayer graphene samples grown by plasma-enhanced
      chemical vapor deposition and transferred onto different substrates with the
      water/polymer-free method were found to preserve their high-quality
      characteristics after the transfer, as manifested by the studies of Raman, X-ray
      and ultraviolet photoemission spectroscopy (XPS and UPS), optical absorption, and
      sheet resistance. Additionally, XPS, UPS and optical absorption studies of fully
      graphene-covered CH3NH3PbI3 thin films showed spectral invariance even after 3
      months, which was in sharp contrast to the drastic spectral changes after merely
      one week in control CH3NH3PbI3 samples without graphene protection. This
      successful demonstration of the graphene-enabled passivation and long-term
      stability of CH3NH3PbI3 thin films therefore opens up a new pathway towards
      realistic photovoltaic applications of hybrid perovskites.

PMID- 29188265
TI  - Forged and fashioned for faithfulness-ruthenium olefin metathesis catalysts
      bearing ammonium tags.
AB  - In this article, the synthesis and applications of selected ammonium tagged Ru
      alkylidene metathesis catalysts were described. Because of the straightforward
      synthesis, the first generation of onium-tagged catalysts have the ammonium group
      installed in the benzylidene ligand. Such catalysts usually give relatively pure
      metathesis products, and are used in polar solvents and water, or immobilised on
      various supports. Later, catalysts tagged in the N-heterocyclic carbene ligand
      (NHC) were developed to offer higher stability and even lower metal contamination
      levels. Due to minimal leaching, the non-dissociating ligand tagged systems were
      successfully immobilised on various supports, including zeolites and Metal
      Organic Frameworks (MOFs) and used in batch and in continuous flow conditions.

PMID- 29188266
TI  - Termination of Ge surfaces with ultrathin GeS and GeS2 layers via solid-state
      sulfurization.
AB  - Reactions of Ge with S vapor, of interest as a potential approach for forming
      thin passivation layers on Ge surfaces, have been studied by photoelectron
      spectroscopy and Raman spectroscopy. Exposure of Ge(100) and Ge(111) to S drives
      the formation of Ge sulfide near-surface layers. At low temperatures, the
      reaction products comprise a thin GeS interlayer terminated by near-surface GeS2.
      Above 400  degrees C, exposure to sulfur gives rise to single-phase GeS2 layers
      whose thickness increases with temperature. Arrhenius analysis of the GeS2
      thickness yields an activation energy (0.63 +/- 0.08) eV, close to the barrier
      that controls Ge oxidation by O radicals. XPS measurements after extended ambient
      exposure show a stable, ultrathin near-surface GeS2 without significant
      oxidation, indicating that Ge-sulfides may provide an effective surface
      passivation for Ge surfaces.

PMID- 29188267
TI  - Control of chemical chaos through medium viscosity in a batch ferroin-catalysed
      Belousov-Zhabotinsky reaction.
AB  - In this paper we show that the active interplay of nonlinear kinetics and
      transport phenomena in a chemical oscillator can be exploited to induce and
      control chaos. To this aim we use as a model system the ferroin-catalysed
      Belousov-Zhabotinsky (BZ) oscillating reaction, which is known to evolve to
      characteristic chaotic transient dynamics when carried out under batch and
      unstirred conditions. In particular, chemical chaos was found to appear and
      disappear by following a Ruelle-Takens-Newhouse (RTN) scenario. Here we use
      medium viscosity as a bifurcation parameter to tune the reaction-diffusion
      convection (RDC) interplay and force the reaction in a specific sequence of
      dynamical regimes: either (i) periodic -> quasi-periodic -> chaotic or (ii)
      periodic -> quasi-periodic or (iii) only periodic. The medium viscosity can be
      set by adding different amounts of surfactant (sodium dodecyl sulphate), known to
      have a little impact on the reaction mechanism, above its critical micelle
      concentration. Experimental results are supported by means of numerical
      simulations of a RDC model, which combines self-sustained oscillations to the
      related chemically-induced buoyancy convection.

PMID- 29188269
TI  - Determining Health Effects of Hazardous Materials Released During Hurricane
      Harvey.

PMID- 29188268
TI  - Sensitivity of Preference-Based Quality-of-Life Measures for Economic Evaluations
      in Early-Stage Melanoma.
AB  - Importance: The diagnosis of a life-threatening disease like melanoma can affect
      all aspects of a person's life, including health-related quality of life (HRQOL)
      and psychological aspects of melanoma such as fear of cancer recurrence (FCR).
      Economic evaluations of psychological interventions require preference-based
      (utility) instruments that are sensitive to changes in well-being and HRQOL;
      however, very few studies have evaluated the sensitivity of these instruments
      when used for people with melanoma. Objective: To compare utility scores from the
      multiple-attribute instrument Assessment of Quality of Life-8-Dimension Scale
      (AQoL-8D) with the mapped utility scores of the Functional Assessment of Cancer
      Therapy-Melanoma (FACT-M) and to investigate the sensitivity of both instruments
      in identifying the influence of FCR on HRQOL. Design, Setting, and Participants:
      This assessment of data from a randomized clinical trial of a psychoeducational
      intervention to reduce FCR, conducted at 3 high-risk melanoma clinics in
      Australia, evaluated 164 patients with early-stage melanoma and a high risk of
      developing a second primary melanoma. Main Outcomes and Measures: The FACT-M and
      AQoL-8D were used to assess HRQOL and FCR among the study participants.
      Concurrent validity was assessed by comparing the total and subdomain scores of
      the 2 instruments, and the strength of associations was assessed using Pearson
      correlation coefficient. Convergent validity was assessed by comparing
      participants' HRQOL, demographic, and clinical characteristics using the chi2
      test and F statistic. Both the FACT-M and AQoL-8D utilities were regressed on FCR
      Inventory (FCRI) severity scores to estimate the effect of elevated FCR on HRQOL.
      Results: A total of 164 participants completed the baseline questionnaires, but
      only 163 met all inclusion criteria and underwent the full analysis: 72 were
      women; 91 were men; and mean (SD) age was 58.2 (12.1) years. Both the AQoL-8D and
      FACT-M instruments showed good concurrent validity and could differentiate
      between relevant subgroups including level of FCRI severity. The AQoL-8D and FACT
      M utilities were strongly correlated (r2 = 0.57). Respondents had a mean (SD)
      AQoL-8D utility of 0.77 (0.2), and a mean (SD) FACT-M utility score of 0.76
      (0.07). High levels of FCRI severity were associated with a decrease in utility
      of 0.12 (95% CI, -0.19 to -0.05) as measured by AQoL-8D, and a decrease of 0.03
      (95% CI, -0.05 to -0.01) as measured by the FACT-M. Conclusions and Relevance:
      For economic evaluations of psychological interventions in melanoma, the AQoL-8D
      and FACT-M are valid measures of utility; however, the AQoL-8D demonstrates
      greater sensitivity to FCRI severity. Our results suggest a significant
      association between FCR and HRQOL.

PMID- 29188271
TI  - A Rare Cause of Small-Bowel Ischemia.

PMID- 29188272
TI  - Allergen Concerns and Popular Skin Care Products-Reply.

PMID- 29188270
TI  - Tracking the Growth of Tense and Agreement in Children With Specific Language
      Impairment: Differences Between Measures of Accuracy, Diversity, and
      Productivity.
AB  - Purpose: Composite measures of children's use of tense and agreement morphology
      differ in their emphasis on accuracy, diversity, or productivity, yet little is
      known about how these different measures change over time. An understanding of
      these differences is especially important for the study of children with specific
      language impairment, given these children's extraordinary difficulty with this
      aspect of grammar. Method: We computed 3 types of composite scores from
      spontaneous speech samples obtained from 17 preschoolers with specific language
      impairment before, during, and after their participation in a language
      intervention study. These measures were the Finite Verb Morphology Composite (a
      measure of accuracy), the Tense Marker Total (a measure of diversity), and the
      Productivity Score (a measure of productivity). Results: The 3 measures differed
      in their growth trajectories. Sample size did not alter the linear or quadratic
      nature of growth of any composite, although it did affect the absolute values
      found for the Tense Marker Total and Productivity Score. Conclusion: Even when
      sample size is controlled, early growth can be seen in tense and agreement
      accuracy with relatively limited diversity and productivity, whereas later growth
      in diversity and productivity can occur with very little change in accuracy.

PMID- 29188273
TI  - Finding a Better Way to Assess Presidential Fitness.

PMID- 29188274
TI  - Which Preschool Children With Specific Language Impairment Receive Language
      Intervention?
AB  - Purpose: Potential biases in service provision for preschool children with
      specific language impairment (SLI) were explored. Method: In Study 1, children
      with SLI receiving treatment (SLI-T) and those with SLI not receiving treatment
      (SLI-NT) were compared on demographic characteristics and developmental
      abilities. Study 2 recruited children with articulation disorders receiving
      treatment (ARTIC-T) to determine if knowing service provision status influenced
      the results of Study 1. Results: In Study 1, the SLI-T group was rated by
      teachers as having poorer executive functioning than children in the SLIT-NT
      group, and the SLI-T group also came from families whose mothers had more
      education. These 2 variables alone predicted SLI-T and SLI-NT group membership
      with 84% accuracy. In Study 2, the ARTIC-T group were perceived as having
      comparable executive functioning to the SLI-NT group and better than the SLI-T
      group, indicating that teachers' knowledge of service provision did not influence
      their ratings of children's executive functioning. Discussion: Preschool children
      with SLI, whose mothers have higher education levels and whose teachers perceive
      them as having poorer executive functioning, are more likely to receive
      intervention. Recognizing service delivery biases is critical for improving early
      provision of intervention for this population.

PMID- 29188275
TI  - What Can Thyroidectomy-Specific Outcomes Teach Us About the American College of
      Surgeons' National Surgical Quality Improvement Program?

PMID- 29188276
TI  - A Potential Role for Adjuvant Chemotherapy and Radiotherapy for Patients With
      High-Risk Bladder Cancer Treated With Cystectomy in the United States.

PMID- 29188277
TI  - Assessment of Symptom Network Density as a Prognostic Marker of Treatment
      Response in Adolescent Depression.

PMID- 29188278
TI  - Comparing Traditional Service Delivery and Telepractice for Speech Sound
      Production Using a Functional Outcome Measure.
AB  - Purpose: Using American Speech-Language-Hearing Association's (ASHA's) National
      Outcomes Measurement System (NOMS) Functional Communication Measure (FCM) as a
      common metric, this investigation compared traditional service delivery and
      telepractice service delivery for children receiving therapy for the NOMS
      diagnostic category of "speech sound production." Method: De-identified cases
      were secured from ASHA's NOMS database and a proprietary database from a private
      e-learning provider. Cases were included if they met 3 criteria: (a) children
      received treatment exclusively for speech sound production, (b) they were between
      6.0 and 9.5 years old, and (c) they received therapy lasting between 4 and 9
      months. A total of 1,331 ASHA NOMS cases and 428 telepractice cases were
      included. The 2 groups were matched by initial FCM scores. Mann-Whitney U tests
      were completed to compare differences in the median change scores (the difference
      between the initial and final FCM scores) between the 2 groups. Results: There
      were no significant differences in the median change scores between the
      traditional group and the telepractice group. Conclusions: These results suggest
      comparable treatment outcomes between traditional service delivery and
      telepractice for treatment of children exhibiting speech sound disorders. The
      findings provide support for the use of telepractice for school-age children.

PMID- 29188279
TI  - Simulation Models of Therapy Intensification in Lipid-Lowering Medicine-Reply.

PMID- 29188280
TI  - Simulation Models of Therapy Intensification in Lipid-Lowering Medicine: Fact or
      Fantasy?

PMID- 29188281
TI  - Assessing the Necessity of Stopping Antithrombotic Agents Before Wide-Awake Hand
      Surgery.

PMID- 29188282
TI  - Laboratory Monitoring During Systemic Terbinafine Therapy for Pediatric
      Onychomycosis.

PMID- 29188283
TI  - Topical Tacalcitol for Family Occurrence of Follicular Keratosis of the Chin.

PMID- 29188284
TI  - Vemurafenib for BRAF V600-Mutant Erdheim-Chester Disease and Langerhans Cell
      Histiocytosis: Analysis of Data From the Histology-Independent, Phase 2, Open
      label VE-BASKET Study.
AB  - Importance: The histiocytic neoplasms Erdheim-Chester disease (ECD) and
      Langerhans cell histiocytosis (LCH) are highly enriched for BRAF V600 mutations
      and have been previously shown to be responsive to treatment with vemurafenib, an
      inhibitor of the BRAF V600 kinase. However, the long-term efficacy and safety of
      prolonged vemurafenib use in these patients are not defined. Here we analyze the
      final efficacy and safety data for vemurafenib in patients with ECD and LCH
      enrolled in the VE-BASKET study. Objective: To determine the efficacy and safety
      of vemurafenib in adults with ECD or LCH enrolled in the VE-BASKET study. Design,
      Setting, and Participants: The VE-BASKET study was an open-label, nonrandomized,
      multicohort study for patients with nonmelanoma cancers harboring the BRAF V600
      mutation. Patients with BRAF V600-mutant ECD or LCH were enrolled in an "other
      solid tumor" cohort of the VE-BASKET study, and they were enrolled in the present
      study. Interventions: Patients received vemurafenib, 960 mg, twice daily
      continuously until disease progression, study withdrawal, or occurrence of
      intolerable adverse effects. Main Outcomes and Measures: The primary end point
      was confirmed objective response rate (ORR) by Response Evaluation Criteria in
      Solid Tumors (RECIST, version 1.1). Secondary end points included progression
      free survival (PFS), overall survival (OS), metabolic response by modified
      positron-emission tomography (PET) Response Criteria in Solid Tumors (PERCIST)
      using 18F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT), and safety.
      Results: A total of 26 patients from the VE-BASKET trial (22 with ECD, 4 with
      LCH) were included in the present study (14 women and 12 men; median age, 61
      years; age range, 51-74 years). The confirmed ORR was 61.5% (95% CI, 40.6%-79.8%)
      in the overall cohort and 54.5% (95% CI, 32.2%-75.6%) in patients with ECD. All
      evaluable patients achieved stable disease or better. The median PFS and OS had
      not been reached in the overall cohort at study closure despite a median follow
      up of 28.8 months; 2-year PFS was 86% (95% CI, 72%-100%), and 2-year OS was 96%
      (95% CI, 87%-100%). All 15 patients evaluated by FDG-PET/CT achieved a metabolic
      response, including 12 patients (80%) with a complete metabolic response. The
      most common adverse events (AEs) in the overall cohort included arthralgia,
      maculopapular rash, fatigue, alopecia, prolonged QT interval, skin papilloma, and
      hyperkeratosis. Hypertension and dermatologic AEs occurred at higher rates than
      those reported in metastatic melanoma. Conclusions and Relevance: In this study,
      vemurafenib had prolonged efficacy in patients with BRAF V600-mutant ECD and LCH
      and warrants consideration as a new standard of care for these patients.

PMID- 29188285
TI  - Association of Exercise Preconditioning With Immediate Cardioprotection: A
      Review.
AB  - Importance: Exercise reduces the risk of cardiovascular events, including through
      an underrecognized, clinically useful form of acute cardioprotection accessible
      after a single episode of exercise, which is called cardiovascular
      preconditioning. Observations: Preclinical evidence shows that 1 to 3 episodes of
      exercise per week will provide strong cardioprotection; gradual, modest
      cardiovascular risk factor modification or physiological artery remodeling cannot
      fully explain these benefits. This review highlights preclinical evidence that
      acute exercise-induced cardiac preconditioning has the ability to activate
      multiple pathways to confer immediate protection against ischemic events, reduce
      the severity of potentially lethal ischemic myocardiac injury, and act as a
      physiological first line of defense. Conclusions and Relevance: Independent of
      the protective benefits of long-term exercise training on risk factors and
      adaptation of the cardiovascular system, cardiovascular preconditioning may
      contribute to the immediate cardioprotection of exercise. In practical terms,
      this means that 1 episode of exercise can create clinically relevant
      cardioprotection.

PMID- 29188286
TI  - Association of Dermatologist Density With the Volume and Costs of Dermatology
      Procedures Among Medicare Beneficiaries.
AB  - Importance: The persistent shortage of dermatologists in the United States
      affects access to care and patient outcomes. Objective: To characterize the
      effect of geographic variations in dermatologist density on the provision of
      dermatology procedures within Medicare. Design, Setting, and Participants: This
      was a cross-sectional study using the 2013 Medicare Provider Utilization and
      Payment Database. Dermatology-related procedures were defined by the top 50
      billing codes accounting for more than 95% of procedures billed by
      dermatologists. Billing codes corresponding to evaluation and monitoring visits
      and dermatopathology were excluded. Total costs were estimated from the Centers
      for Medicare & Medicaid Services physician fee schedule, based on the nonfacility
      national payment amount with no modifiers. Nationally representative
      administrative database that includes 100% of charges billed by noninstitutional
      clinicians covered under Medicare Part B. A total of 10 391 dermatologists
      practicing within the 50 states and Washington, DC, were included. The Medicare
      eligible population was defined as all persons 65 years or older. Exposures:
      Density of dermatologists, categorized into first (5.3 per 100 000 persons >=65
      years) through fifth (54.8 per 100 000 persons >=65 years) quintiles. Main
      Outcomes and Measures: Utilization of dermatology procedures (mean volume per 100
      000 persons >=65 years) and total cost (mean amount billed per person >=65 years)
      by clinician type across quintiles of dermatologist density. Results: In 2013,
      dermatologists billed Medicare for 28 million procedures costing $2.21 billion.
      Mean billed amount by dermatologists per person 65 years or older was $15.87 in
      the lowest-density quintile vs $92.02 in the highest-density quintile. This trend
      suggests that each interval increase of 10 dermatologists per 100 000 persons 65
      years or older is correlated with a $14.81 increase in Medicare spending on
      dermatology procedures (95% CI, 8.28-21.34; P = .005). Utilization of these
      procedures differed among clinician types, with dermatologists largely performing
      destruction of premalignant lesions and PCPs primarily doing injections.
      Conclusions and Relevance: There is evidence of supply-sensitive variation in the
      provision of dermatology procedures for the Medicare-eligible population; higher
      dermatologist density is correlated with increased utilization of dermatology
      procedures and subsequent billed charges to Medicare. Further research is needed
      to determine the effect of such variations on outcomes and whether incentives can
      better align dermatologists with areas of clinical need.

PMID- 29188287
TI  - Allergen Concerns and Popular Skin Care Products.

PMID- 29188288
TI  - Allergen Concerns and Popular Skin Care Products.

PMID- 29188289
TI  - Coronary Calcium Score and Cardiovascular Risk in Elderly Populations-Reply.

PMID- 29188290
TI  - War-Related Traumas and Mental Health Across Generations.

PMID- 29188291
TI  - Journal of Biomechanical Engineering: Legacy Paper 2017.

PMID- 29188292
TI  - Association of the World War II Finnish Evacuation of Children With Psychiatric
      Hospitalization in the Next Generation.
AB  - Importance: Although there is evidence that adverse childhood experiences are
      associated with worse mental health in adulthood, scarce evidence is available
      regarding an emerging concern that the next generation might also be affected.
      Objective: To compare the risk of psychiatric hospitalization in cousins whose
      parents were vs were not exposed to the Finnish evacuation policy that involved a
      mean 2-year stay with a Swedish foster family. Design, Setting, and Participants:
      This multigenerational, population-based cohort study of Finnish individuals and
      their siblings born between January 1, 1933, and December 31, 1944, analyzed the
      association of evacuee status as a child during World War II in the first
      generation with the risk of psychiatric hospitalization among offspring in the
      second generation. Evacuee status during World War II was determined using the
      Finnish National Archive's registry of participants in the Finnish evacuation.
      Data on evacuee status were linked to the psychiatric diagnoses in the Finnish
      Hospital Discharge Register from January 1, 1971, through December 31, 2012, for
      offspring (n = 93 391) born between January 1, 1950, and December 31, 2010. Sex
      specific Cox proportional hazards regression models were used to estimate hazard
      ratios for risk of psychiatric hospitalization during the follow-up period.
      Because offspring of evacuees and their nonevacuated siblings are cousins, the
      Cox proportional hazards regression models included fixed effects to adjust for
      confounding factors in families. Data analysis was performed from June 15, 2016,
      to August 26, 2017. Exposures: Parental participation in the evacuation during
      World War II (coded 1 for parents who were evacuated and placed in foster care
      and 0 for those not evacuated). Main Outcomes and Measures: Offspring's initial
      admission to the hospital for a psychiatric disorder, obtained from the Finnish
      Hospital Discharge Register from January 1, 1971, through December 31, 2012.
      Results: Of the 93 391 study persons, 45 955 (49.2%) were women and 47 436 (50.8)
      were men; mean (SD) age in 2012 among survivors was 45.4 (6.58) years. Female
      offspring of mothers evacuated to Sweden during childhood had an elevated risk of
      psychiatric hospitalization (hazard ratio for any type of psychiatric disorder:
      2.04 [95% CI, 1.04-4.01]; hazard ratio for mood disorder: 4.68 [95% CI, 1.92
      11.42]). There was no excess risk of being hospitalized for a psychiatric
      disorder among women whose fathers were exposed to the Finnish evacuation policy
      during World War II or among men whose mothers or fathers were exposed.
      Conclusions and Relevance: In a prior follow-up study of the Finnish evacuees,
      girls evacuated to Swedish foster families during World War II were more likely
      to be hospitalized for a psychiatric disorder-in particular, a mood disorder-in
      adulthood than their nonevacuated sisters. The present study found that the
      offspring of these individuals were also at risk for mental health problems that
      required hospitalization and suggests that early-life adversities, including war
      related exposures, may be associated with mental health disorders that persist
      across generations.

PMID- 29188293
TI  - Variation of Thyroidectomy-Specific Outcomes Among Hospitals and Their
      Association With Risk Adjustment and Hospital Performance.
AB  - Importance: Current surgical quality metrics might be insufficient to fully judge
      the quality of certain operations because they are not procedure specific.
      Hypocalcemia, recurrent laryngeal nerve (RLN) injury, and hematoma are considered
      to be the most relevant outcomes to measure after thyroidectomy. Whether these
      outcomes can be used as hospital quality metrics is unknown. Objectives: To
      evaluate whether thyroidectomy-specific outcomes vary among hospitals, whether
      the addition of thyroidectomy-specific variables affects risk adjustment, and
      whether differences in hospital performance are associated with thyroidectomy
      specific care processes. Design, Setting, and Participants: In this retrospective
      cohort study, patients undergoing thyroidectomies from January 1, 2013, through
      December 31, 2015, at hospitals participating in the American College of
      Surgeons' National Surgical Quality Improvement Program were studied. Exposure:
      Thyroidectomy-related care. Main Outcomes and Measures: Clinically severe
      hypocalcemia, RLN injury, and clinically significant hematoma within 30 days of
      thyroid surgery and hospital-level performance variation, change in risk
      adjustment, and association with processes. Results: Overall, 14 540 patients
      (mean [SD] age, 52.1 [15.0] years; 11 499 [79.1%] female) underwent operations at
      98 hospitals. Because operations missing thyroidectomy-specific outcomes were
      excluded, the numbers of operations and hospitals analyzed differed by outcome.
      Of 14 540 operations included, clinically severe hypocalcemia occurred in 450
      patients (3.3% overall, 0.6% after partial, and 4.7% after subtotal or total
      thyroidectomy), RLN injury in 755 patients (5.7% overall, 4.2% after partial, and
      6.6% after subtotal or total thyroidectomy), and hematoma in 175 patients (1.3%).
      Hospital performance varied for hypocalcemia and RLN injury but not for hematoma.
      Hospital performance rankings were largely unaffected by the inclusion of
      thyroidectomy-specific data in risk adjustment. With regard to processes,
      patients undergoing thyroidectomies at the best-performing vs worst-performing
      hospitals less frequently had their postoperative parathyroid hormone level
      measured (593 [19.9%] vs 457 [31.7%], P < .001) and more often were prescribed
      oral calcium, vitamin D, or both (2281 [76.6%] vs 962 [66.8%], P < .001). When
      profiled by RLN injury, use of energy devices (1517 [69.1%] vs 507 [55.2%], P <
      .001) and intraoperative nerve monitoring (1223 [55.7%] vs 346 [37.7%], P < .001)
      were more prevalent at the best- compared with the worst-performing hospitals.
      Conclusions and Relevance: Postoperative hypocalcemia and RLN injury, but not
      hematoma, potentially could be used as thyroidectomy-specific national hospital
      quality improvement metrics. Strategies aimed at reducing these complications
      after thyroidectomy may improve the care of these patients.

PMID- 29188294
TI  - Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic
      Aneurysm: A Meta-analysis.
AB  - Importance: Risk factors for abdominal aortic aneurysm (AAA) are largely unknown,
      which has hampered the development of nonsurgical treatments to alter the natural
      history of disease. Objective: To investigate the association between lipid
      associated single-nucleotide polymorphisms (SNPs) and AAA risk. Design, Setting,
      and Participants: Genetic risk scores, composed of lipid trait-associated SNPs,
      were constructed and tested for their association with AAA using conventional
      (inverse-variance weighted) mendelian randomization (MR) and data from
      international AAA genome-wide association studies. Sensitivity analyses to
      account for potential genetic pleiotropy included MR-Egger and weighted median
      MR, and multivariable MR method was used to test the independent association of
      lipids with AAA risk. The association between AAA and SNPs in loci that can act
      as proxies for drug targets was also assessed. Data collection took place between
      January 9, 2015, and January 4, 2016. Data analysis was conducted between January
      4, 2015, and December 31, 2016. Exposures: Genetic elevation of low-density
      lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C),
      and triglycerides (TG). Main Outcomes and Measures: The association between
      genetic risk scores of lipid-associated SNPs and AAA risk, as well as the
      association between SNPs in lipid drug targets (HMGCR, CETP, and PCSK9) and AAA
      risk. Results: Up to 4914 cases and 48 002 controls were included in our
      analysis. A 1-SD genetic elevation of LDL-C was associated with increased AAA
      risk (odds ratio [OR], 1.66; 95% CI, 1.41-1.96; P = 1.1 * 10-9). For HDL-C, a 1
      SD increase was associated with reduced AAA risk (OR, 0.67; 95% CI, 0.55-0.82; P
      = 8.3 * 10-5), whereas a 1-SD increase in triglycerides was associated with
      increased AAA risk (OR, 1.69; 95% CI, 1.38-2.07; P = 5.2 * 10-7). In
      multivariable MR analysis and both MR-Egger and weighted median MR methods, the
      association of each lipid fraction with AAA risk remained largely unchanged. The
      LDL-C-reducing allele of rs12916 in HMGCR was associated with AAA risk (OR, 0.93;
      95% CI, 0.89-0.98; P = .009). The HDL-C-raising allele of rs3764261 in CETP was
      associated with lower AAA risk (OR, 0.89; 95% CI, 0.85-0.94; P = 3.7 * 10-7).
      Finally, the LDL-C-lowering allele of rs11206510 in PCSK9 was weakly associated
      with a lower AAA risk (OR, 0.94; 95% CI, 0.88-1.00; P = .04), but a second
      independent LDL-C-lowering variant in PCSK9 (rs2479409) was not associated with
      AAA risk (OR, 0.97; 95% CI, 0.92-1.02; P = .28). Conclusions and Relevance: The
      MR analyses in this study lend support to the hypothesis that lipids play an
      important role in the etiology of AAA. Analyses of individual genetic variants
      used as proxies for drug targets support LDL-C lowering as a potential effective
      treatment strategy for preventing and managing AAA.

PMID- 29188295
TI  - Association of Environment With the Risk of Developing Psychotic Disorders in
      Rural Populations: Findings from the Social Epidemiology of Psychoses in East
      Anglia Study.
AB  - Importance: Social determinants are important risk factors for the development of
      first-episode psychosis (FEP); their effects in rural areas are largely unknown.
      Objective: To investigate neighborhood-level factors associated with FEP in a
      large, predominantly rural population-based cohort. Design, Setting, and
      Participants: This study extracted data on referrals for treatment of potential
      FEP at 6 Early-Intervention Psychosis services from the Social Epidemiology of
      Psychoses in East Anglia naturalistic cohort study data set, which covered a
      population of more than 2 million people in a rural area in the East of England
      for a period of 3.5 years. All individuals aged 16 to 35 years who presented to
      Early-Intervention Psychosis services and met diagnostic criteria for first
      episodes of nonaffective psychoses and affective psychoses (International
      Statistical Classification of Diseases and Related Health Problems, Tenth
      Revision diagnostic codes F20-33) were included (n = 631). Persons whose
      disorders had an organic basis (diagnostic codes F06.X) and those meeting the
      criteria for substance-induced psychosis (diagnostic codes F1X.5) were excluded.
      We derived 4 neighborhood-level exposures from a routine population data set
      using exploratory factor analysis (racial/ethnic diversity, deprivation,
      urbanicity, and social isolation) and investigated intragroup racial/ethnic
      density and fragmentation. Main Outcomes and Measures: Multilevel Poisson
      regression was performed to determine associations between incidence rates and
      neighborhood-level factors, after adjustment for individual factors. Results were
      reported as incidence rate ratios (IRRs). Results: The study included 631
      participants who met criteria for FEP and whose median age at first contact was
      23.8 years (interquartile range, 19.6-27.6 years); 416 of 631 (65.9%) were male.
      Crude incidence of FEP was calculated as 31.2 per 100 000 person-years (95% CI,
      28.9-33.7). Incidence varied significantly between neighborhoods after adjustment
      for age, sex, race/ethnicity, and socioeconomic status. For nonaffective
      psychoses, incidence was higher in neighborhoods that were more economically
      deprived (IRR, 1.13; 95% CI, 1.06-1.20) and socially isolated (IRR, 1.11; 95% CI,
      1.04-1.19). It was lower in more racially/ethnically diverse neighborhoods (IRR,
      0.94; 95% CI, 0.87-1.00). Higher intragroup racial/ethnic density (IRR, 0.97; 95%
      CI, 0.94-1.00) and lower intragroup racial/ethnic fragmentation (IRR, 0.98; 95%
      CI, 0.96-1.00) were associated with a reduced risk of affective psychosis.
      Conclusions and Relevance: Spatial variation in the incidence of nonaffective and
      affective psychotic disorders exists in rural areas. This suggests that the
      social environment contributes to psychosis risk across the rural-urban gradient.

PMID- 29188297
TI  - Coronary Calcium Score and Cardiovascular Risk in Elderly Populations: Further
      Considerations.

PMID- 29188299
TI  - Are work organization interventions effective in preventing or reducing work
      related musculoskeletal disorders? A systematic review of the literature.
AB  - Objectives We sought to determine whether interventions that target work
      organization or the psychosocial work environment are effective in preventing or
      reducing work-related musculoskeletal disorders (WMSD) compared to usual work.
      Methods We systematically reviewed the 2000-2015 English- and French-language
      scientific literature, including studies evaluating the effectiveness of an
      organizational or psychosocial work intervention on incidence, prevalence or
      intensity of work-related musculoskeletal pain or disorders in the neck,
      shoulders, upper limbs and/or back or of work absence due to such problems, among
      non-sick-listed workers. We excluded rehabilitation and individual-level
      behavioral interventions and studies with >50% attrition. We analyzed medium- and
      high-quality studies and synthesized the evidence using the Grading of
      Recommendations Assessment, Development & Evaluation (GRADE) approach. An
      analysis of key workplace intervention elements supplemented the interpretation
      of results. Results We identified 884 articles; 28 met selection criteria,
      yielding 2 high-quality, 10 medium-quality and 16 low-quality studies. There was
      moderate evidence that supplementary breaks, compared to conventional break
      schedules, are effective in reducing symptom intensity in various body regions.
      Evidence was low-to-very-low quality for other interventions, primarily due to
      risk of bias related to study design, high attrition rates, co-interventions, and
      insensitive indicators. Most interventions lacked key intervention elements, such
      as work activity analysis and ergonomist guidance during implementation, but the
      relation of these elements to intervention effectiveness or ineffectiveness
      remains to be demonstrated. Conclusions Targeting work-rest cycles may reduce
      WMSD. Better quality studies are needed to allow definitive conclusions to be
      drawn on the effectiveness of other work organizational or psychosocial
      interventions to prevent or reduce WMSD.

PMID- 29188298
TI  - Adjuvant Sandwich Chemotherapy Plus Radiotherapy vs Adjuvant Chemotherapy Alone
      for Locally Advanced Bladder Cancer After Radical Cystectomy: A Randomized Phase
      2 Trial.
AB  - Importance: Locoregional failure for patients with locally advanced bladder
      cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and
      is associated with high morbidity and mortality. Adjuvant radiotherapy (RT) can
      decrease locoregional failure but has not been studied in the chemotherapy era.
      Objective: To investigate if adjuvant sequential RT plus chemotherapy can improve
      locoregional recurrence-free survival (LRFS) compared with adjuvant chemotherapy
      alone. Design, Setting, and Participants: A randomized phase 3 trial was opened
      to compare adjuvant RT vs sequential chemotherapy plus RT after RC for LABC, but
      a third arm was added later as a randomized phase 2 trial to compare chemotherapy
      plus RT vs adjuvant chemotherapy alone, an emerging standard. The intent-to-treat
      phase 2 trial reported herein enrolled patients from December 2002 to July 2008.
      Data were analyzed from August 3, 2015, to January 6, 2016. Routine follow-up and
      surveillance pelvic computed tomographic (CT) scans every 6 months during the
      first 2 years were performed. The setting was an academic center. Patients with
      bladder cancer 70 years or younger having 1 or more risk factors (>=pT3b, grade
      3, or positive nodes) with negative margins after radical cystectomy plus pelvic
      lymph node dissection were eligible. Patients had Eastern Cooperative Oncology
      Group performance status of 0 to 2, no evidence of distant metastases on CT scan
      of the abdomen and pelvis or on chest imaging, and adequate renal, hepatic, and
      hematologic function. Ninety-one percent (109 of 120) had >= pT3 disease.
      Interventions: Chemotherapy plus RT included 2 cycles of gemcitabine (1000 mg/m2
      intravenously on days 1, 8, and 15) and cisplatin (70 mg/m2 intravenously on day
      2) before and after RT to 4500 cGy in 150 cGy twice-daily fractions over 3 weeks
      using 3-dimensional conformal techniques. Chemotherapy alone included 4 cycles of
      gemcitabine and cisplatin. Main Outcome and Measure: Locoregional recurrence-free
      survival. Results: The chemotherapy plus RT arm accrued 75 patients, and the
      chemotherapy-alone arm accrued 45 patients, with a weighted randomization to
      speed accrual. Fifty-three percent (64 of 120) had urothelial carcinoma, and
      46.7% (56 of 120) had squamous cell carcinoma or other. The arms were balanced
      except for age (median, 52 vs 55 years; P = .04) and tumor size (mean, 4.9 vs 5.8
      cm; P < .01), both favoring chemotherapy plus RT. Two-year outcomes and overall
      adjusted hazard ratios (HRs) for chemotherapy plus RT vs chemotherapy alone were
      96% vs 69% (HR, 0.08; 95% CI, 0.02-0.39; P < .01) for LRFS, 68% vs 56% (HR, 0.53;
      95% CI, 0.27-1.06; P = .07) for disease-free survival, and 71% vs 60% (HR, 0.61;
      95% CI, 0.33-1.11; P = .11) for overall survival (OS). Five patients (7%) had RT
      associated late grade 3 gastrointestinal tract adverse effects in the
      chemotherapy plus RT arm. Conclusions and Relevance: Adjuvant chemotherapy plus
      RT was reasonably well tolerated and was associated with significant improvements
      in LRFS and marginal improvements in disease-free survival vs chemotherapy alone
      in LABC. The addition of adjuvant RT should be considered for LABC. This regimen
      warrants further study in phase 3 trials. Trial Registration: clinicaltrials.gov
      Identifier: NCT01734798.

PMID- 29188296
TI  - Association of Cerebral Amyloid-beta Aggregation With Cognitive Functioning in
      Persons Without Dementia.
AB  - Importance: Cerebral amyloid-beta aggregation is an early event in Alzheimer
      disease (AD). Understanding the association between amyloid aggregation and
      cognitive manifestation in persons without dementia is important for a better
      understanding of the course of AD and for the design of prevention trials.
      Objective: To investigate whether amyloid-beta aggregation is associated with
      cognitive functioning in persons without dementia. Design, Setting, and
      Participants: This cross-sectional study included 2908 participants with normal
      cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the
      multicenter Amyloid Biomarker Study. Normal cognition was defined as having no
      cognitive concerns for which medical help was sought and scores within the normal
      range on cognitive tests. Mild cognitive impairment was diagnosed according to
      published criteria. Study inclusion began in 2013 and is ongoing. Data analysis
      was performed in January 2017. Main Outcomes and Measures: Global cognitive
      performance as assessed by the Mini-Mental State Examination (MMSE) and episodic
      memory performance as assessed by a verbal word learning test. Amyloid
      aggregation was measured with positron emission tomography or cerebrospinal fluid
      biomarkers and dichotomized as negative (normal) or positive (abnormal) according
      to study-specific cutoffs. Generalized estimating equations were used to examine
      the association between amyloid aggregation and low cognitive scores (MMSE score
      <=27 or memory z score<=-1.28) and to assess whether this association was
      moderated by age, sex, educational level, or apolipoprotein E genotype. Results:
      Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years),
      amyloid positivity was associated with low memory scores after age 70 years (mean
      difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and
      21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores
      (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI
      (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low
      memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean
      difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association
      decreased with age. Low cognitive scores had limited utility for screening of
      amyloid positivity in persons with normal cognition and those with MCI. In
      persons with normal cognition, the age-related increase in low memory score
      paralleled the age-related increase in amyloid positivity with an intervening
      period of 10 to 15 years. Conclusions and Relevance: Although low memory scores
      are an early marker of amyloid positivity, their value as a screening measure for
      early AD among persons without dementia is limited.

PMID- 29188300
TI  - Favorable versus unfavorable prognostic groups by post-chemoradiation FDG-PET
      imaging in node-positive esophageal squamous cell carcinoma patients treated with
      definitive chemoradiotherapy.
AB  - PURPOSE: Our purpose was to examine the prognostic value of post-CRT PET based on
      the presence or absence of FDG-avid metastatic lymph node(s) and metabolic
      response of the primary tumor in patients with clinically node-positive ESCC
      treated with definitive chemoradiotherapy (dCRT). METHODS: We identified 108
      eligible patients treated by chemoradiotherapy (CRT) with or without resection
      from our prospectively collected database. Absence of FDG-avid metastatic lymph
      node with at least partial response of the primary tumor on PET scan after
      initial CRT was defined as the Post-CRT PET favorable group (yPET-F), and
      otherwise as unfavorable group (yPET-U). The Kaplan-Meier method and Cox
      regression were performed for survival analyses and multivariable analysis,
      respectively. RESULTS: The study cohort was comprised of 59 patients receiving
      dCRT. Forty-five patients receiving trimodality therapy (TMT) comprised the
      comparative group and four patients were excluded from further analyses for
      developing interval distant metastasis detected on post-CRT PET scan. The median
      follow-up for the study cohort was 41 months. On K-M analysis of the study
      cohort, yPET-F was found to have significantly better OS (2-year: 72.5% vs 13.7%,
      p < 0.01) and DMFS (2-year: 71.6% vs 36.6%, p = 0.01) than yPET-U. In
      multivariable analysis, yPET-F remained as a strong independent favorable
      prognosticator on both OS (HR 0.08, p < 0.01) and DMFS (HR 0.14, p = 0.02) for
      the dCRT cohort. Compared with TMT cohort, for yPET-U patients, TMT had better OS
      (p = 0.03) than dCRT-Operable and dCRT-Operable had superior OS (p = 0.04) than
      dCRT-Unresectable. For yPET-F patients, there was no difference in both OS (p >
      0.99) and DMFS (p = 0.92) between these three groups. CONCLUSIONS: Absence of FDG
      avid metastatic lymph node with at least partial response of the primary tumor on
      PET scan after CRT (i.e., yPET-F status) prognosticate for excellent OS and DMFS
      in cN+ ESCC patients treated with dCRT, and might be comparable to TMT.

PMID- 29188301
TI  - Organic Amendments in a Long-term Field Trial-Consequences for the Bulk Soil
      Bacterial Community as Revealed by Network Analysis.
AB  - This study intended to elucidate the long-term effects of organic soil amendments
      on bacterial co-occurrence in bulk soil with and without addition of mineral
      fertiliser. Previous research mostly neglected the bacterial co-occurrence
      structure and focussed mainly on the parameters species diversity and abundance
      changes of species. Here we present a systematic comparison of two frequently
      used soil amendments, manure and straw, with regard to their impact on bacterial
      co-occurrence in a long-term field trial in Speyer, Germany. The approach
      involved 16S amplicon sequencing in combination with a bacterial network
      analysis, comparing the different fertiliser regimes. The results show an
      increase of bacterial diversity as well as an accumulation of bacteria of the
      order Bacillales in plots fertilised with manure compared to a control treatment.
      In the straw-amended plots neither an increase in diversity was found nor were
      indicative species detectable. Furthermore, network analysis revealed a clear
      impact of mineral fertiliser addition on bacterial co-occurrence structure. Most
      importantly, both organic amendments increased network complexity irrespective of
      mineral fertilisation regime. At the same time, the effects of manure and straw
      exhibited differences that might be explained by differences in their
      nutritional/chemical contents. It is concluded that bacterial interactions are a
      crucial parameter for the assessment of amendment effects regarding soil health
      and sustainability.

PMID- 29188302
TI  - Bamboo Specialists from Two Mammalian Orders (Primates, Carnivora) Share a High
      Number of Low-Abundance Gut Microbes.
AB  - Bamboo specialization is one of the most extreme examples of convergent
      herbivory, yet it is unclear how this specific high-fiber diet might selectively
      shape the composition of the gut microbiome compared to host phylogeny. To
      address these questions, we used deep sequencing to investigate the nature and
      comparative impact of phylogenetic and dietary selection for specific gut
      microbial membership in three bamboo specialists-the bamboo lemur (Hapalemur
      griseus, Primates: Lemuridae), giant panda (Ailuropoda melanoleuca, Carnivora:
      Ursidae), and red panda (Ailurus fulgens, Carnivora: Musteloideadae), as well as
      two phylogenetic controls-the ringtail lemur (Lemur catta) and the Asian black
      bear (Ursus thibetanus). We detected significantly higher Shannon diversity in
      the bamboo lemur (10.029) compared to both the giant panda (8.256; p = 0.0001936)
      and the red panda (6.484; p = 0.0000029). We also detected significantly enriched
      bacterial taxa that distinguished each species. Our results complement previous
      work in finding that phylogeny predominantly governs high-level microbiome
      community structure. However, we also find that 48 low-abundance OTUs are shared
      among bamboo specialists, compared to only 8 OTUs shared by the bamboo lemur and
      its sister species, the ringtail lemur (Lemur catta, a generalist). Our results
      suggest that deep sequencing is necessary to detect low-abundance bacterial OTUs,
      which may be specifically adapted to a high-fiber diet. These findings provide a
      more comprehensive framework for understanding the evolution and ecology of the
      microbiome as well as the host.

PMID- 29188303
TI  - Analysis of petrous apex meningocele associated with meningioma: is there any
      relation with chronic intracranial hypertension?
AB  - PURPOSE: Petrous apex meningocele (PAM) is an uncommon cystic lesion involving
      the petrous apex. The underlying cause of PAM may be related to chronic elevated
      intracranial pressure. The aim of the study was to explore the relationship
      between PAM and meningioma and between PAM and other intracranial hypertension
      findings. METHODS: Two hundred seventy-eight consecutive patients with
      meningiomas were retrospectively studied. Fifty age- and gender-matched controls
      were also enrolled in this study. The incidence of PAM, empty sella, tortuosity
      of the optic nerve, and hydrops of optic nerve sheath was evaluated. The maximum
      width, area, volume of each PAM, or Meckel's cave and volume of meningioma were
      measured in controls and patients, separately. RESULTS: One hundred fifty-nine
      (57.19%) patients were detected with coexistent PAMs. One hundred twenty-five
      patients had bilateral PAMs, 34 had unilateral lesions, and the remaining 119 did
      not have PAM. Two subjects (4/50) had unilateral PAMs in normal controls. The
      maximum width, area, volume of PAM, or Meckel's cave were significantly larger in
      the patients with bilateral PAM group than those in the unilateral PAM group, in
      the group without PAM, and those in control group (p = 0.000). The volume of
      meningioma was positively correlated with the PAM volume (r = 0.48). There was a
      positive correlation for the incidence between PAM and (1) empty sella (r =
      0.901) and (2) tortuosity of the optic nerves and hydrops of the optic sheath (r
      = 0.825). CONCLUSION: Coexistence of PAMs with meningiomas is not rare in
      incidence, and it suggests a potential role for chronically elevated intracranial
      pressure and disturbance of CSF circulation in their pathophysiology.

PMID- 29188304
TI  - Diagnostic accuracy of CTA and MRI/MRA in the evaluation of the cortical venous
      reflux in the intracranial dural arteriovenous fistula DAVF.
AB  - PURPOSE: Computed tomography angiography (CTA) and magnetic resonance
      imaging/angiography (MRI/MRA) are used for the diagnosis of intracranial dural
      arteriovenous fistulas (DAVFs). The purpose of this study was to compare the
      diagnostic accuracy of CTA and magnetic resonance imaging/angiography (MRI/MRA)
      for detection of cortical venous reflux (CVR) in intracranial DAVFs. METHODS: The
      records of patients with angiography-confirmed intracranial DAVFs who also
      received CTA and MRI/MRA from January 2008 to July 2016 were reviewed. CTA and
      MRI/MRA were reviewed for signs of CVR, and the diagnostic accuracy of individual
      signs was evaluated by receiver operating curve (ROC) analysis. RESULTS: A total
      108 patients were included in this study. CTA signs of CVR included abnormal
      dilatation, early enhancement, and the presence of a medullary or pial vein.
      MRI/MRA signs of CVR included abnormal dilatation, early enhancement, flow
      related enhancement, flow void, and medullary or pial venous collaterals. The
      sensitivity of individual CTA signs ranged from 62 to 96%, and specificities from
      79 to 94%. The sensitivities of individual MRI/MRA signs ranged from 58 to 83%,
      and specificities from 77 to 93%. The area under ROC curve (AUC) of CTA and
      MRI/MRA were 0.91 and 0.87, respectively (P = 0.04 in direct comparison). In
      subgroup analysis, CTA had better diagnostic accuracy for higher grade disease (P
      = 0.05) and non-aggressive manifestation (P = 0.04). CONCLUSIONS: Both CTA and
      MRI/MRA have good diagnostic accuracy for detection of CVR in patients with
      intracranial DAVFs. There is modest evidence that CTA is better than MRI/MRA.

PMID- 29188305
TI  - Synergistic cytotoxicity of a prostate cancer-specific immunotoxin in combination
      with the BH3 mimetic ABT-737.
AB  - In many tumors, including prostate cancer, anti-apoptotic members of the Bcl-2
      family are overexpressed and cause cell death resistance, which is a typical
      hallmark of cancer. Different therapeutic approaches, therefore, aim to restore
      the death mechanisms for enhanced apoptosis. Our recombinant immunotoxin D7(VL
      VH)-PE40 is composed of the scFv D7(VL-VH) against the prostate-specific membrane
      antigen (PSMA) on the surface of prostate cancer cells and of the cytotoxic
      domain of the bacterial toxin Pseudomonas Exotoxin A (PE40). Since Pseudomonas
      Exotoxin A-based immunotoxins are known to preferentially inhibit the expression
      of the anti-apoptotic protein Mcl-1, the rationale was to test our immunotoxin in
      combination with the BH3 mimetic ABT-737, which specifically inhibits Bcl-2, Bcl
      xl, and Bcl-w for enhanced induction of apoptosis in prostate cancer cells. The
      immunotoxin showed high and specific binding and cytotoxicity against PSMA
      expressing prostate cancer cells marked by a direct inhibition of Mcl-1. The
      combination of the immunotoxin with a subtoxic concentration of ABT-737 caused
      additive or even synergistic effects, which were based on an enhanced apoptosis
      induction as detected by poly(ADP-ribose) polymerase (PARP) and Caspase-3
      cleavage in Western blot. Our study shows that the combination therapy of
      immunotoxin plus ABT-737 is a promising approach for the future treatment of
      advanced prostate cancer to improve therapeutic efficacy and to reduce adverse
      side effects.

PMID- 29188307
TI  - [Criteria for resectability of pancreatic cancer and postoperative imaging].
AB  - By improving the techniques of pancreatic surgery, the mortality and morbidity
      for pancreatic carcinoma could be significantly reduced. For radiologists a
      profound knowledge of the surgical techniques is of decisive importance. Based on
      this knowledge postoperative complications can be reliably uncovered and local
      recurrences can be detected at an early stage. The complications resulting from
      pancreatic surgery can be severe and often necessitate a radiological
      intervention. As pancreatic cancer itself is a severe disease with a poor 5-year
      survival, which can only be improved by an R0 resection, it is crucial to
      identify using imaging those patients who are primarily operable or who can
      potentially achieve an operable condition through neoadjuvant chemotherapy
      (borderline) and inoperable patients to avoid postoperative complications which
      would additionally weaken them and result in unnecessary delays in initiating
      palliative therapy. Thus, familiarity with the clinical criteria of resectability
      and also inoperability in pancreatic cancer nowadays represents an essential
      basic knowledge for every oncological radiologist.

PMID- 29188306
TI  - Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the
      EU project IMMOMEC.
AB  - Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine
      cancer. Its carcinogenesis may be either caused by the clonal integration of the
      Merkel cell polyomavirus into the host genome or by UV-induced mutations.
      Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable
      signaling pathways such as RB restriction of cell cycle progression or p53
      inactivation. Despite its low incidence, MCC recently received much attention
      based on its exquisite immunogenicity and the resulting major success of immune
      modulating therapies. Here, we summarize current knowledge on epidemiology,
      biology and therapy of MCC as conclusion of the project 'Immune Modulating
      strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5
      year period by the European Commission to investigate innovative immunotherapies
      for MCC.

PMID- 29188308
TI  - Ureteroscopy from the recent past to the near future.
AB  - Stone surgery is one of oldest surgical practices undertaken by man. Hippocrates
      refused to let his followers "cut for the stone" and it was only in February
      1980, when the first human trial of shock wave therapy on a renal stone was
      performed with success that a new era in minimally invasive treatment (surgery)
      for stones was opened up and this condemnation was finally resolved in the
      Hippocratic Oath. Endoscopy, using natural orifices, supported by anaesthesia,
      incremented by technology and with access to all points along the urinary tract,
      began by competing with ESWL, but is now the treatment of choice in most cases.
      As far as we know humans have always had stones. First, lithiasis was endemic
      bladder stones in children, now it is renal in general. Added to this a number of
      well-known risk factors, a rapid increase in obesity in the population, as well
      as bariatric surgery for its treatment, are causing an increase in the prevalence
      and recurrence of lithiasis everywhere. A short history of the advances made with
      the introduction and development of the ureteroscope, along with auxiliary
      devices, will show why this is the preferred technique at the moment for treating
      lithiasis in general and for treating stones in pregnant women, children and the
      obese in particular. Being a minimally invasive surgery, with a low morbidity and
      a very high efficiency and stonefree rate, has become established as a clear
      future technique for both adults and children. This development is not only due
      to technological advancements, but also to the routine use of the Holmium: YAG
      LASER for intracorporeal lithotripsy, capable of destroying any stone regardless
      of its composition or location, surpassing the ability of any other lithotripter.
      It is also due to the development of devices that allow access to the ureter and
      all parts of the kidney, as well as auxiliary aids to assist in the handling of
      stones during treatment. New LASERs, robotic control of the fdURS and digital
      imaging, as well as disposable devices, have had and, indeed, continue to have a
      unique impact on future development in this field. However, success will continue
      to depend on the careful choice of fURS, energy source and ancillary instruments
      obtained by the urologist during both real life and virtual training in human
      simulators.

PMID- 29188309
TI  - Optimization of ultrahigh-speed multiplex PCR for forensic analysis.
AB  - In this paper, we demonstrate the design and optimization of an ultrafast PCR
      amplification technique, used with a seven-locus multiplex that is compatible
      with conventional capillary electrophoresis systems as well as newer microfluidic
      chip devices. The procedure involves the use of a high-speed polymerase and a
      rapid cycling protocol to permit multiplex PCR amplification of forensic short
      tandem repeat loci in 6.5 min. We describe the selection and optimization of
      master mix reagents such as enzyme, buffer, MgCl2, and dNTPs, as well as primer
      ratios, total volume, and cycle conditions, in order to get the best profile in
      the shortest time possible. Sensitivity and reproducibility studies are also
      described. The amplification process utilizes a small high-speed thermocycler and
      compact laptop, making it portable and potentially useful for rapid, inexpensive
      on-site genotyping. The seven loci of the multiplex were taken from conventional
      STR genotyping kits and selected for their size and lack of overlap. Analysis was
      performed using conventional capillary electrophoresis and microfluidics with
      fluorescent detection. Overall, this technique provides a more rapid method for
      rapid sample screening of suspects and victims. Graphical abstract Rapid
      amplification of forensic DNA using high speed thermal cycling followed by
      capillary or microfluidic electrophoresis.

PMID- 29188311
TI  - Differences by Veteran/civilian status and gender in associations between
      childhood adversity and alcohol and drug use disorders.
AB  - PURPOSE: To examine differences by US military Veteran status and gender in
      associations between childhood adversity and DSM-5 lifetime alcohol and drug use
      disorders (AUD/DUD). METHODS: We analyzed nationally representative data from
      3119 Veterans (n = 379 women; n = 2740 men) and 33,182 civilians (n = 20,066
      women; n = 13,116 men) as provided by the 2012-2013 National Epidemiologic Survey
      on Alcohol and Related Conditions (NESARC-III). We used weighted multinomial
      logistic regression, tested interaction terms, and calculated predicted
      probabilities by Veteran status and gender, controlling for covariates. To test
      which specific moderation contrasts were statistically significant, we conducted
      pairwise comparisons. RESULTS: Among civilians, women had lower AUD and DUD
      prevalence than men; however, with more childhood adversity, this gender gap
      narrowed for AUD and widened for DUD. Among Veterans, in contrast, similar
      proportions of women and men had AUD and DUD; with more childhood adversity, AUD
      predicted probability among men surpassed that of women. Childhood adversity
      elevated AUD probability among civilian women to levels exhibited by Veteran
      women. Among men, Veterans with more childhood adversity were more likely than
      civilians to have AUD, and less likely to have DUD. CONCLUSIONS: Childhood
      adversity alters the gender gap in AUD and DUD risk, and in ways that are
      different for Veterans compared with civilians. Department of Defense, Veterans
      Affairs, and community health centers can prevent and ameliorate the harmful
      effects of childhood adversity by adapting existing behavioral health efforts to
      be trauma informed, Veteran sensitive, and gender tailored.

PMID- 29188310
TI  - Untreated illness and recovery in clients of an early psychosis intervention
      program: a 10-year prospective cohort study.
AB  - PURPOSE: To investigate whether duration of untreated psychosis (DUP) and
      duration of untreated illness (DUI) are associated with measures of both
      subjective and objective recovery 10 years after a first episode of psychosis.
      METHODS: A cohort of 65 clients from an early psychosis intervention program
      completed a battery of outcome measures 10 years following initial treatment for
      first-episode psychosis (FEP). The outcomes of interest were self-perceived
      recovery scores (Maryland Assessment of Recovery in People with Serious Mental
      Illness Scale) and occupational activity, defined as engagement in work and/or
      school on a full/part-time basis. Multiple linear and logistic regression
      analyses were used to estimate the associations between DUP and DUI with each
      measure of recovery, adjusting for potential confounding factors. RESULTS: We did
      not find a statistically significant association between DUP and either
      occupational activity (OR = 1.26, 95% CI 0.81-1.95) or self-perceived recovery
      score (beta = - 0.73, 95% CI - 2.42 to 0.97). However, we found a significant
      negative association between DUI and self-perceived recovery score (beta = -
      0.52, 95% CI - 0.87 to - 0.16). CONCLUSIONS: Our findings suggest that DUI may
      have a stronger influence than DUP on recovery from FEP at 10-year follow-up.
      This suggests the potential value in targeted interventions for people with a
      long DUI to increase the likelihood of achieving recovery after the first episode
      of psychosis.

PMID- 29188312
TI  - Physical therapists as first-line diagnosticians for traumatic acute rotator cuff
      tears: a prospective study.
AB  - BACKGROUND: Early diagnosis of traumatic acute full-thickness rotator cuff tears
      (FTRCT) is important to offer early surgical repair. Late repairs following fatty
      infiltration of the rotator cuff muscles have less favorable results. We think
      that physical therapists are valuable diagnosticians in a screening process. The
      objective of this study was to evaluate the usefulness of physical therapists as
      first-line diagnosticians in detecting acute traumatic FTRCT. METHODS: Between
      November 2010 and January 2014, 394 consecutive patients having an age between 18
      and 75 years who sought medical care because of acute shoulder trauma with acute
      onset of pain, limited abduction and negative plain radiographs were included in
      the study. A clinical assessment was conducted by a physical therapist 1 week
      after the trauma. The patients were divided into three groups by the physical
      therapist according to the findings: FTRCT (Group I, n = 122); sprain (Group II,
      n = 62); or other specific diagnoses (Group III, n = 210). Group III patients
      were discharged and excluded from the study. Magnetic Resonance Imaging shoulder
      was performed for all Group I patients and for all patients with persistent
      symptoms in Group II. RESULTS: 79/184 patients had FTRCTs documented by MRI in
      groups I and II. The clinical assessment of the physical therapist had a
      sensitivity of 85%, specificity of 68%, and usefulness index of 0.45 (> 0.35
      considered useful) for diagnosing FTRCT. CONCLUSION: Physical therapists can be
      useful as first-line diagnosticians in detecting traumatic FTRCT.

PMID- 29188314
TI  - The Effect of Cholesterol on the Dielectric Structure of Lipid Bilayers.
AB  - Cholesterol plays an important role in regulating the properties of phospholipid
      bilayers and many mechanisms have been proposed to explain why cholesterol is so
      ubiquitous within biological membranes of animals. Here we present the results of
      studies on the effect of cholesterol on the electrical/dielectric properties of
      lipid membranes tethered to a solid substrate. These tethered bilayer lipid
      membranes tBLM were formed on a commercially available chemically modified gold
      substrate. These lipid bilayers are very robust. Very high-resolution electrical
      impedance spectroscopy (EIS) was used to determine the dielectric structure of
      the lipid bilayers and associated interfaces. The EIS data allowed the dielectric
      substructure of the lipid bilayers to be determined. The results showed that when
      cholesterol was present in the tethered membranes at a concentration of 10%
      (mol/mol); the thickness of the tBLMs increased and the membrane conductance
      decreased. However, when cholesterol was present in the tethered membrane at more
      than 30% (mol/mol) the effect of cholesterol was dramatically different; the
      membranes then became thinner and possessed a much larger electrical conductance.
      The EIS allowed a distinction to be made between a hydrophobic region in the
      center of the bilayer and another hydrophobic region further out towards the
      polar head region, in addition to the polar head region itself. Cholesterol was
      found to have the largest effect on the inner, hydrophobic region, although the
      outer hydrophobic region was also affected.

PMID- 29188313
TI  - Arteriovenous Fistula Maturation Failure in a Large Cohort of Hemodialysis
      Patients in the Netherlands.
AB  - OBJECTIVES: Radiocephalic arteriovenous fistulas (RCAVF) are the preferred
      vascular access (VA) for hemodialysis (HD). Cohort studies from North America
      revealed that nonmaturation is a significant disadvantage of RCAVFs compared to
      other VAs. DESIGN: This present retrospective study describes the incidence of
      nonmaturation of AVFs and functional failure of arteriovenous grafts (AVG) in a
      multicentre cohort in the Netherlands and attempts to create a prediction model
      for nonmaturation of RCAVFs. Furthermore, the efficacy of interventions to
      promote maturation as well as the variability between hemodialysis centers was
      evaluated. MATERIALS: Medical records from 8 hospitals from 1997 to 2016 were
      retrospectively evaluated for VA type, maturation/primary success and
      demographics and comorbidities. METHODS: A prediction model was created for RCAVF
      nonmaturation using multivariate logistic regression analysis, selecting
      significant predictors using backward selection. Discrimination and calibration
      of the model were assessed. RESULTS: 1383 AVFs and 273 AVGs were included in 1221
      patients. Overall nonmaturation was 24% for RCAVFs, and 11% for upper arm AVFs.
      The functional failure rate for AVGs was 6%. The nonmaturation rate of
      contralateral RCAVFs after failure of an RCAVF was 22%. Procedures to improve
      RCAVF maturation were successful in 98/142 cases (69%). Predictors for
      nonmaturation were female gender, peripheral vascular disease, cerebrovascular
      disease and a cephalic vein diameter <2.5 mm, but the prediction model lacked
      sensitivity and specificity predicting individual RCAVF nonmaturation (C
      statistic 0.629). CONCLUSION: Nonmaturation rates are highest for RCAVFs, but
      nonmaturation could not be predicted with demographic parameters.

PMID- 29188315
TI  - High prevalence of hepatitis B virus infection in patients with aggressive B cell
      non-Hodgkin's lymphoma in China.
AB  - We retrospectively analyzed a large study to investigate the association of
      hepatitis B virus (HBV) with aggressive B cell non-Hodgkin's lymphoma (aggressive
      B-NHL) in China, where HBV is endemic. HBV was present in 39 aggressive B-NHL
      patients (10.46%), 13 indolent B-NHL patients (5.09%), 12 multiple myeloma (MM)
      patients (3.67%), and 5 solitary plasmacytoma (SP) patients (6.67%). HBV
      infection was significantly associated with increased risks for aggressive B-NHL
      (P < 0.01). HBV seems to have a very important role in the pathogenesis of
      aggressive B-NHL in China.

PMID- 29188316
TI  - Impact of Bicuspid Aortic Valve Morphology on Aortic Valve Disease and Aortic
      Dilation in Pediatric Patients.
AB  - Bicuspid aortic valve (BAV) is the most common congenital heart defect. BAV is
      associated with aortic stenosis and insufficiency, and aortic dilation in adult
      groups, but data in pediatric groups are limited. We sought to assess the impact
      of BAV morphology on aortic valve disease and aortic dilation in pediatric
      patients. We performed a retrospective review of all echocardiograms in patients
      with isolated BAV who were followed at our institution from July 2002 to July
      2012. BAV morphology, aortic valve stenosis and/or insufficiency, and aortic
      dimensions were measured manually. Comparisons were made between right-left cusp
      fusion (RL) and right-noncoronary cusp fusion (RN) BAV morphologies. Generalized
      least square models were fit to analyze the impact of specific variables on
      aortic dilation. There were 1075 echocardiograms in 366 patients (72% male) with
      isolated BAV. Aortic valve insufficiency and stenosis were more common in RN (p <
      0.001 for both). The median aortic sinus Z score was higher in the RL (0.47; IQR 
      0.31 to 1.44) than in the RN group (0.02; - 0.83 to 0.82) (p < 0.001). There was
      no difference in median ascending aorta Z score between groups. Patients with the
      highest weights had larger aortas (p < 0.001), but the absolute difference
      between the highest and lowest weight groups was small (1.5 mm). The impact of
      BAV morphology on aortic valve disease and aortic dilation in pediatric patients
      presages that seen in adults. Patient body weight does not make significant
      clinical impacts on aortic diameters, suggesting that Z scores for aortic
      diameters should be based on ideal body weights.

PMID- 29188317
TI  - Genetic Testing in Pediatric Cardiomyopathy.
AB  - Genetic testing is recommended in patients with dilated cardiomyopathy (DCM);
      however, limited studies demonstrate high yields of genetic testing in non
      hypertrophic (HCM) patients. Furthermore, there is sparse genotype-phenotype data
      in pediatric DCM patients. We performed a retrospective review of 70 consecutive
      probands with cardiomyopathy (non-HCM) who underwent genetic evaluation. Mean age
      at presentation was 5.48 years. Echocardiography revealed mean ejection fraction
      of 32.4%. The LVEDd z score ranged from - 5.7 to + 15.9. Cardiomyopathy was
      classified as dilated in 56, 10 with non-compaction, 2 with restrictive, and 2
      with ARVC. TTN gene mutations were the most common gene involved. Genetic testing
      was negative in 16/70 (23%) giving a yield of 77% including VUS. 33% (23/70) of
      probands had a positive family history among whom the diagnostic yield was 57%
      (13/23) for pathogenic mutations. Yield for positive genetic testing in the DCM
      with positive family history group was 9/18 (50%). There were 6 deaths (9%) and
      26/70 (37%) underwent transplantation. More frequent cardiac transplantations (48
      vs. 34%) and deaths (17 vs. 2%) were seen in mutation-positive vs. mutation
      negative subgroups. This study demonstrates an increasing yield of genetic
      testing in DCM although with a high rate of VUS detection. Use of genetic
      information for better management and prognostication will require big data
      analysis.

PMID- 29188318
TI  - Myocardial Strain Using Cardiac MR Feature Tracking and Speckle Tracking
      Echocardiography in Duchenne Muscular Dystrophy Patients.
AB  - Duchenne muscular dystrophy (DMD) is an inherited X-linked disorder with an
      incidence of 1 in 3500 male births, and cardiomyopathy is becoming the leading
      cause of death. While Cardiac MRI (CMR) and late gadolinium enhancement (LGE) are
      important tools in recognizing myocardial involvement, myocardial strain imaging
      may demonstrate early changes and allow patients to avoid gadolinium contrast. We
      performed CMR feature tracking (FT) and echo-based speckle tracking (STE) strain
      measures on DMD patients and age/sex matched controls who had received a CMR with
      contrast and transthoracic echocardiogram. Data were collected for longitudinal
      strain in the apical four-chamber view and circumferential strain in the mid
      papillary parasternal short axis. Segmental wall analysis was performed and
      compared with the presence of LGE. Data were analyzed using student's t tests or
      one-way ANOVA adjusting for multiple comparisons. We measured 24 subjects with
      DMD and 8 controls. Thirteen of 24 DMD subjects were LGE positive only in the
      lateral segments in short-axis views. Average circumferential strain (CS)
      measured by FT was significantly decreased in DMD compared to controls (- 18.8 +/
      6.1 vs. - 25.5 +/- 3.2; p < 0.001) and showed significant differences in the
      anterolateral, inferolateral, and inferior segments. Average CS by STE trended
      towards significance (p = 0.06) but showed significance in only the inferior
      segment. FT showed significant differences in the inferolateral segment between
      LGE positive (- 15.5 +/- 9.0) and LGE negative (- 18.2 +/- 8.3) in DMD subjects
      compared to controls (- 28.6 +/- 7.3; p <= 0.04). FT also showed significant
      differences between anteroseptal and inferolateral segments within LGE-positive
      (p < 0.003) and LGE-negative (p < 0.03) DMD subjects while STE did not. There
      were no significant differences in longitudinal strain measures. CMR-FT-derived
      myocardial strain was able to demonstrate differences between subjects with DMD
      and controls not detected by STE. FT was also able to demonstrate differences in
      LGE-positive and LGE-negative segments within patients with DMD. FT may be able
      to predict LGE-positive segments in DMD without the use of gadolinium contrast.

PMID- 29188319
TI  - A dedicated paracentesis clinic decreases healthcare utilization for serial
      paracenteses in decompensated cirrhosis.
AB  - PURPOSE: The purpose of the study is to describe the effect of a dedicated
      paracentesis clinic on healthcare utilization by patients with decompensated
      cirrhosis and refractory ascites. METHODS: This Institutional Review Board
      approved retrospective study identified cirrhotic patients receiving paracenteses
      over a 6-month period before and after creating the paracentesis clinic. Patients
      were followed for 12 months to collect outcome data including characteristics of
      subsequent hospitalizations and paracenteses. Logistic regression was used to
      examine the association between the paracentesis clinic and outcomes. RESULTS:
      There were 183 patients and 1364 paracenteses performed during the study time
      period. Age, gender, cirrhosis etiology, MELD, Child-Pugh, and Charlson
      comorbidity index were comparable between the two groups. Rates of mortality,
      transplant, and hospitalization were also similar during 1 year follow-up. After
      establishment of the paracentesis clinic, median paracenteses per patient
      increased from 2 (IQR 1-7) to 4 (IQR 2-11) (P = 0.01); albumin replacement after
      paracenteses >= 5 L improved from 76.3% to 91.7% (P < 0.001); and the fraction of
      outpatient paracenteses performed in the emergency department decreased from
      13.4% to 3.8% (P < 0.001). Major complications remained negligible at 0.81%
      across both time periods. While fewer patients were admitted for ascites after
      the paracentesis clinic (39.6% vs. 20.8%, P = 0.009), more patients had acute
      kidney injury (AKI) during follow-up (47.2% vs. 65.9%, P = 0.02), with a trend
      towards more AKI admissions (22.6% vs. 35.4%, P = 0.09). CONCLUSION: A dedicated
      paracentesis clinic can improve access and wait times, while also reducing
      admissions for ascites and paracenteses performed in the emergency department.

PMID- 29188320
TI  - Characterization of a New Ezakiella Isolated from the Human Vagina: Genome
      Sequence and Description of Ezakiella massiliensis sp. nov.
AB  - The study of the vaginal microbiota using the "culturomics concept" allowed us to
      isolate, from the vaginal swab of an asymptomatic 20-year-old woman who had
      sexual relations with another woman with bacterial vaginosis, an unknown Gram
      positive anaerobic coccus-shaped bacterium that was designated strain Marseille
      P2951T and characterized using taxono-genomics. Strain Marseille-P2951T is non
      motile and non-spore forming and exhibits catalase and oxidase activities. Its
      16S rRNA gene-based identification showed 98.5% identity with Ezakiella
      peruensis, the phylogenetically closest species. The major fatty acids are
      C18:1n9 (58%) and C16:0 (22%). With a 1,741,785 bp length, the G+C content of the
      genome is 36.69%. Of a total of 1657 genes, 1606 are protein-coding genes and 51
      RNAs. Also, 1123 genes are assigned a putative function and 127 are ORFans.
      Phenotypic, phylogenetic, and genomics analyses revealed that strain Marseille
      P2951T (=CSUR P2951 =DSM 103122) is distinct and represents a new species of the
      genus Ezakiella, for which the name Ezakiella massiliensis sp. nov. is proposed.

PMID- 29188322
TI  - Mass balance, metabolic disposition, and pharmacokinetics of a single oral dose
      of regorafenib in healthy human subjects.
AB  - PURPOSE: To evaluate the mass balance, metabolic disposition, and
      pharmacokinetics of a single dose of regorafenib in healthy volunteers. In
      addition, in vitro metabolism of regorafenib in human hepatocytes was
      investigated. METHODS: Four healthy male subjects received one 120 mg oral dose
      of regorafenib containing approximately 100 uCi (3.7 MBq) [14C]regorafenib.
      Plasma concentrations of parent drug were derived from HPLC-MS/MS analysis and
      total radioactivity from liquid scintillation counting (LSC). Radiocarbon
      analyses used HPLC with fraction collection followed by LSC for all urine
      samples, plasma, and fecal homogenate extracts. For the in vitro study,
      [14C]regorafenib was incubated with human hepatocytes and analyzed using HPLC-LSC
      and HPLC-HRMS/MS. RESULTS: Regorafenib was the major component in plasma, while
      metabolite M-2 (pyridine N-oxide) was the most prominent metabolite. Metabolites
      M-5 (demethylated pyridine N-oxide) and M-7 (N-glucuronide) were identified as
      minor plasma components. The mean concentration of total radioactivity in
      plasma/whole blood appeared to plateau at 1-4 h and again at 6-24 h post-dose. In
      total, 90.5% of administered radioactivity was recovered in the excreta within a
      collection interval of 12 days, most of which (71.2%) was eliminated in feces,
      while excretion via urine accounted for 19.3%. Regorafenib (47.2%) was the most
      prominent component in feces and was not excreted into urine. Excreted
      metabolites resulted from oxidative metabolism and glucuronidation. CONCLUSIONS:
      Regorafenib was eliminated predominantly in feces as well as by hepatic
      biotransformation. The multiple biotransformation pathways of regorafenib
      decrease the risk of pharmacokinetic drug-drug interactions.

PMID- 29188321
TI  - Comparative Analyses of Methanogenic and Methanotrophic Communities Between Two
      Different Water Regimes in Controlled Wetlands on the Qinghai-Tibetan Plateau,
      China.
AB  - Wetlands are an important methane (CH4) emission source. CH4 is mainly produced
      during the biogeochemical process, in which methanogens and methanotrophs both
      play important roles. However, little is known how these two microbial
      communities change under different water regimes. In this study, the diversity
      and abundance of methanogens and methanotrophs in wetlands on Qinghai-Tibetan
      Plateau with different water contents (a high water content site DZ2-14-3 and a
      low water content site DZ2-14-4) were studied by using phylogenetic analysis and
      quantitative PCR based on mcrA gene and pmoA gene. A total of 16 methanogenic
      operational taxonomic units (OTUs) and 9 methanotrophic OTUs are obtained. For
      methanogens, Fen cluster (58.0%) and Methanosaetaceae (20.3%) are the dominant
      groups in high moisture samples, whereas Methanosaetaceae (32.4%),
      Methanosarcinaceae (29.4%), and Methanobacteriaceae (22.1%) are prevalent in low
      moisture samples. Methylobacter (90.0%) of type I methanotrophs are
      overwhelmingly dominant in high moisture samples, while Methylocystis (53.3%) and
      Methylomonas (42.2%) belonging to types II and I methanotrophs are the
      predominant groups in low moisture samples. Furthermore, qPCR analysis revealed
      that the abundance of methanogens and methanotrophs were higher in high moisture
      samples than that in low moisture samples. Overall, this comparative study
      between wetlands controlled by two different water regimes on the Qinghai-Tibetan
      Plateau provides fundamental data for further research on microbial functions
      within extreme ecosystems.

PMID- 29188323
TI  - Evolution of social media: review of the role of podcasts in gynaecology.
AB  - Podcasts are an emerging social media phenomenon in medicine, originating from
      critical care specialities and now expanding to other domains. Aided by the rapid
      increase in popularity of social media platforms and the advantage of
      accessibility, universality and portability, there has been a slow but
      significant expansion of podcast use in gynaecology. Current literature suggests
      that there is potential for digital communication to enhance dissemination of
      information, however there is conflicting evidence on its ability to increase
      users' knowledge. Emerging interest in urogynaecology presents an opportunity for
      the subspeciality to tailor podcasts to the needs of its users. In this review,
      the origins, current evidence and future trends in the use of podcasts in
      urogynaecology are explored.

PMID- 29188324
TI  - Total vaginectomy and urethral lengthening at time of neourethral prelamination
      in transgender men.
AB  - INTRODUCTION AND HYPOTHESIS: For transgender men (TGM), gender-affirmation
      surgery (GAS) is often the final stage of their gender transition. GAS involves
      creating a neophallus, typically using tissue remote from the genital region,
      such as radial forearm free-flap phalloplasty. Essential to this process is
      vaginectomy. Complexity of vaginal fascial attachments, atrophy due to
      testosterone use, and need to preserve integrity of the vaginal epithelium for
      tissue rearrangement add to the intricacy of the procedure during GAS. We
      designed the technique presented here to minimize complications and contribute to
      overall success of the phalloplasty procedure. METHODS: After obtaining approval
      from the Institutional Review Board, our transgender (TG) database at the
      University of Miami Hospital was reviewed to identify cases with vaginectomy and
      urethral elongation performed at the time of radial forearm free-flap
      phalloplasty prelamination. Surgical technique for posterior vaginectomy and
      anterior vaginal wall-flap harvest with subsequent urethral lengthening is
      detailed. RESULTS: Six patients underwent total vaginectomy and urethral
      elongation at the time of radial forearm free-flap phalloplasty prelamination.
      Mean estimated blood loss (EBL) was 290 +/- 199.4 ml for the vaginectomy and
      urethral elongation, and no one required transfusion. There were no
      intraoperative complications (cystotomy, ureteral obstruction, enterotomy,
      proctotomy, or neurological injury). One patient had a urologic complication
      (urethral stricture) in the neobulbar urethra. CONCLUSIONS: Total vaginectomy and
      urethral lengthening procedures at the time of GAS are relatively safe
      procedures, and using the described technique provides excellent tissue for
      urethral prelamination and a low complication rate in both the short and long
      term.

PMID- 29188326
TI  - Bioavailability of Metsulfuron and Sulfentrazone Herbicides in Soil as Affected
      by Amendment with Two Contrasting Willow Biochars.
AB  - This study investigated the effect of two willow (Salix spp.) biochars, produced
      using either fast- or slow-pyrolysis, on the bioavailability of metsulfuron and
      sulfentrazone herbicides in soil. Five rates (0%, 1%, 2%, 3%, and 4%; w/w) of
      each biochar were used, along with varying rates of metsulfuron (0-3.2 ug ai kg
      1) and sulfentrazone (0-200 ug ai kg-1), followed by a sugar beet bioassay. The
      fast-pyrolysis biochar had minimal effect, while the slow-pyrolysis biochar
      decreased the bioavailability of both herbicides. Despite using the same
      feedstock, the two biochars had different physical and chemical properties, of
      which specific surface area was most contrasting (3.0 and 175 m2 g-1 for fast-
      and slow-pyrolysis biochar, respectively). Increased anionic herbicide adsorption
      associated with greater surface area of the slow-pyrolysis biochar is considered
      to be the primary mechanism responsible for reducing herbicide bioavailability
      with this biochar.

PMID- 29188325
TI  - Pregnancy impact on uterosacral ligament and pelvic muscles using a 3D numerical
      and finite element model: preliminary results.
AB  - INTRODUCTION AND HYPOTHESIS: We studied the geometry of and changes in structures
      that play an important role in stabilizing the pelvic system during pregnancy
      using a numerical system at different gestational ages and postpartum. METHODS:
      We developed a parturient numerical model to assess pelvic structures at
      different gestational stages (16, 32, and 38 weeks) and postpartum (2 months and
      1 year) using magnetic resonance imaging (MRI). Organs, muscles, and ligaments
      were segmented to generate a 3D model of the pelvis. We studied changes in the
      length of uterosacral ligaments (USL) and thickness of the puborectal portion of
      the levator ani muscle (LAM) during and after pregnancy. We used this model to
      perform finite element (FE) simulation and analyze deformations of these
      structures under stress from the increase in uterine weight. RESULTS: Analysis
      reveals an increase in the length of US ligaments at 16, 32, and 38 weeks. Two
      months after delivery, it decreases without returning to the length at 16 weeks
      of pregnancy. Similar changes were observed for the puborectal portion of the
      LAM. Variations observed in these structures are not equivalent to other
      anatomical structures of pelvic suspension. FE simulation with increased uterus
      weight does not lead to those findings. CONCLUSION: This analysis brings new
      elements and a new focus for discussion relating to changes in pelvic balance of
      parturient women that are not simply linked to the increase in uterine volume.

PMID- 29188327
TI  - Spatial and Ontogenetic Variation in Mercury in Lake Superior Basin Sea Lamprey
      (Petromyzon marinus).
AB  - Mercury concentrations were measured in eggs, larvae, and adult spawning-phase
      sea lampreys (Petromyzon marinus) collected in tributaries of Lake Superior to
      investigate spatial and ontogenetic variation. There were significant differences
      in mercury concentrations between all three life stages, with levels highest in
      adults (mean = 3.01 ug/g), followed by eggs (mean = 0.942 ug/g), and lowest in
      larvae (mean = 0.455 ug/g). There were no significant differences in mercury
      concentrations by location for any life stage or by sex in adults. Mercury was
      not correlated with adult or larval lamprey length or mass. Mercury levels in
      adult lampreys exceeded U.S. and Canadian federal guidelines for human
      consumption. Mercury concentrations in all life stages exceeded criteria for the
      protection of piscivorous wildlife, posing a threat to local fish, birds, and
      mammals. High mercury levels in adult lampreys combined with their semelparous
      life history make them a potential source of lake-derived mercury to spawning
      streams.

PMID- 29188328
TI  - Hydrocarbon Degradation and Lead Solubility in a Soil Polluted with Lead and Used
      Motor Oil Treated by Composting and Phytoremediation.
AB  - Used lubricant oils and metals can be common soil pollutants in abandoned sites.
      When soil is contaminated with various hazardous wastes, the efficiency of
      biological treatments could be affected. The purpose of this work was to
      investigate the effect of combining phytoremediation and composting on the
      efficiency of hydrocarbon degradation and lead solubility in a soil contaminated
      with 31,823 mg/kg of total petroleum hydrocarbon (TPH) from used motor oil and
      8260 mg/kg of lead. Mexican cactus (Opuntia ficus indica) and yard trimmings were
      added in the composting process, and lucerne (Medicago sativa) was used in the
      phytoremediation process. After a 9 week composting process, only 13% of the
      initial TPH concentration was removed. The following 20 week phytoremediation
      process removed 48% of TPH. The highest TPH degradation percentage (66%), was
      observed in the experiment with phytoremediation only. This work demonstrates
      sustainable technologies, such as biological treatments, represent low-cost
      options for remediation; however, they are not frequently used because they
      require long periods of time for success.

PMID- 29188329
TI  - Water Quality and Management Changes Over the History of Poland.
AB  - Poland is one of the countries distinguished by a long and colorful past.
      Undergoing numerous turbulent socio-economic changes forced by the course of
      history, Poland is now one of the member states of the European Union.
      Experiencing low water quantity and high contamination levels in surface waters,
      Poland is following other EU countries in the effort to reach a "good" water
      status. Herein are presented impacts of changes in Polish history on water
      legislation, management, and research, as well as explanations for the
      perceptible split between engineering and scientific approaches to the aquatic
      issues. Drawbacks caused by unsatisfactory state research funding for the
      sciences and division of the water related contemporary scientific interests are
      also discussed.

PMID- 29188330
TI  - Metabolic pathway of 6-aminohexanoate in the nylon oligomer-degrading bacterium
      Arthrobacter sp. KI72: identification of the enzymes responsible for the
      conversion of 6-aminohexanoate to adipate.
AB  - Arthrobacter sp. strain KI72 grows on a 6-aminohexanoate oligomer, which is a by
      product of nylon-6 manufacturing, as a sole source of carbon and nitrogen. We
      cloned the two genes, nylD 1 and nylE 1 , responsible for 6-aminohexanoate
      metabolism on the basis of the draft genomic DNA sequence of strain KI72. We
      amplified the DNA fragments that encode these genes by polymerase chain reaction
      using a synthetic primer DNA homologous to the 4-aminobutyrate metabolic enzymes.
      We inserted the amplified DNA fragments into the expression vector pColdI in
      Escherichia coli, purified the His-tagged enzymes to homogeneity, and performed
      biochemical studies. We confirmed that 6-aminohexanoate aminotransferase (NylD1)
      catalyzes the reaction of 6-aminohexanoate to adipate semialdehyde using alpha
      ketoglutarate, pyruvate, and glyoxylate as amino acceptors, generating glutamate,
      alanine, and glycine, respectively. The reaction requires pyridoxal phosphate
      (PLP) as a cofactor. For further metabolism, adipate semialdehyde dehydrogenase
      (NylE1) catalyzes the oxidative reaction of adipate semialdehyde to adipate using
      NADP+ as a cofactor. Phylogenic analysis revealed that NylD1 should be placed in
      a branch of the PLP-dependent aminotransferase sub III, while NylE1 should be in
      a branch of the aldehyde dehydrogenase superfamily. In addition, we established a
      NylD1/NylE1 coupled system to quantify the aminotransferase activity and to
      enable the conversion of 6-aminohexaoate to adipate via adipate semialdehyde with
      a yield of > 90%. In the present study, we demonstrate that 6-aminohexanoate
      produced from polymeric nylon-6 and nylon oligomers (i.e., a mixture of 6
      aminohexaoate oligomers) by nylon hydrolase (NylC) and 6-aminohexanoate dimer
      hydrolase (NylB) reactions are sequentially converted to adipate by metabolic
      engineering technology.

PMID- 29188331
TI  - A type D ferulic acid esterase from Streptomyces werraensis affects the volume of
      wheat dough pastries.
AB  - A type D ferulic acid esterase (FAE) was identified in the culture supernatant of
      Streptomyces werraensis, purified, sequenced, and heterologously produced in E.
      coli BL21(DE3)Star by co-expressing chaperones groES-groEL (69 U L-1). The unique
      enzyme with a mass of about 48 kDa showed no similarity to other FAEs, and only
      moderate homology (78.5%) to a Streptomycete beta-xylosidase. The purified
      reSwFAED exhibited a temperature optimum of 40  degrees C, a pH optimum in the
      range from pH seven to eight and a clear preference for bulky natural substrates,
      such as 5-O-trans-feruloyl-L-arabinofuranose (FA) and beta-D-xylopyranosyl-(1->2)
      5-O-trans-feruloyl-L-arabinofuranose (FAX), compared to the synthetic standard
      substrate methyl ferulate. Treatment of wheat dough with as little as 0.03 U or
      0.3 U kg-1 reSwFAED activity resulted in a significant increase of the bun volume
      (8.0 or 9.7%, resp.) after baking when combined with polysaccharide-degrading
      enzymes from Aspergillus. For the first time, the long-standing, but rarely
      proven positive effect of a FAE in baking was confirmed.

PMID- 29188333
TI  - Dynamically tensioned ACL functional knee braces reduce ACL and meniscal strain.
AB  - PURPOSE: The effectiveness of ACL functional knee braces to reduce meniscal and
      ACL strain after ACL injury or reconstruction is not well understood. A new
      dynamic knee tensioning brace system has been designed to apply an active
      stabilizing force to the knee. The ability of this system to reduce tissue
      strains is unknown. The purpose of this study was to test the ability of the
      dynamically tensioned brace to reduce strain in both the ACL and meniscus during
      rehabilitation activities. METHODS: A combined in vivo/in silico/in vitro method
      was used to study three activities: gait, double leg squat, and single leg squat.
      Muscle forces and kinematics for each activity were derived through in vivo
      motion capture and applied to seven cadaveric knee specimens fitted with custom
      braces. Medial meniscal strain and ACL strain were measured in ACL intact,
      deficient and reconstructed conditions. RESULTS: The brace lowered peak and
      average meniscal strain in ACL deficient knees (P < 0.05) by an average of 1.7%.
      The brace was also found to lower meniscal strain in reconstructed knees (1.1%)
      and lower ACL strain in ACL intact (1.3%) and reconstructed knees (1.4%) (P <
      0.05). CONCLUSIONS: This study supports the use of a brace equipped with a
      dynamic tensioning system to lower meniscal strain in ACL-deficient knees. Its
      use may help decrease the risk of subsequent meniscal tears in chronic ACL
      deficiency or delayed reconstruction. In ACL-intact and reconstructed knees, the
      brace may be beneficial in injury prophylaxis or in protecting the ACL graft
      following reconstruction. These results will aid clinicians make informed
      recommendations for functional brace use in patients with unstable knees. LEVEL
      OF EVIDENCE: II.

PMID- 29188332
TI  - "I never made it to the pros..." Return to sport and becoming an elite athlete
      after pediatric and adolescent anterior cruciate ligament injury-Current evidence
      and future directions.
AB  - The management of anterior cruciate ligament (ACL) injuries in the skeletally
      immature and adolescent patient remains an area of controversy in sports
      medicine. This study, therefore, summarizes and discusses the current evidence
      related to treating pediatric and adolescent patients who sustain an ACL injury.
      The current literature identifies a trend towards ACL reconstruction as the
      preferred treatment option for ACL injuries in the young, largely justified by
      the risk of further structural damage to the knee joint. Worryingly, a second ACL
      injury is all too common in the younger population, where almost one in every
      three to four young patients who sustain an ACL injury and return to high-risk
      pivoting sport will go on to sustain another ACL injury. The clinical experience
      of these patients emphasizes the rarity of an athlete who makes it to elite level
      after a pediatric or adolescent ACL injury, with or without reconstruction. If
      these patients are unable to make it to an elite level of sport, treatment should
      possibly be modified to take account of the risks associated with returning to
      pivoting and strenuous sport. The surveillance of young athletes may be
      beneficial when it comes to reducing injuries. Further research is crucial to
      better understand specific risk factors in the young and to establish independent
      structures to allow for unbiased decision-making for a safe return to sport after
      ACL injury. Level of evidence V.

PMID- 29188334
TI  - Increased in vivo patellofemoral loading after total knee arthroplasty in
      resurfaced patellae.
AB  - PURPOSE: The primary purpose of the study was to investigate if and how patellar
      bone tracer uptake (BTU) distribution in SPECT/CT is influenced by patellar
      resurfacing and the position of femoral and tibial TKA component position.
      METHODS: A total of 104 knees of 103 consecutive patients who underwent primary
      TKA were prospectively investigated. Primary patellar resurfacing was done in 40
      knees while 64 had a TKA without patellar resurfacing. All patients underwent
      clinical assessment using the knee society score (KSS) and standardized
      radiographs and Tc-99m-HDP-SPECT/CT before and 12 and 24 months after TKA.
      Measurements of BTU including intensity and anatomical distribution pattern in
      eight different patellar regions were performed. Tibial and femoral TKA component
      position was assessed from 3D reconstructed CT data. Patellar height, thickness
      and tilt were measured and the distance between the tibial tuberosity and the
      trochlear groove (TT-TG) was measured. Univariate analysis was performed to
      identify differences between the two groups (p < 0.05). RESULTS: Significantly
      higher BTU was found in the anterior, non-articular, areas of the patella in
      patients who underwent patellar resurfacing (p < 0.05). The BTU pattern was
      similar between the groups, as the maximal uptake in both groups was seen in the
      superior posterior parts and the minimal uptake was seen in the inferior anterior
      parts. The mean postoperative KSS was significantly higher in the unresurfaced
      group after 12 months (p < 0.05), but with no significant difference after 24
      months. CONCLUSIONS: Based on the findings of the present study, patellar
      resurfacing is related to significantly higher BTU in the anterior parts of the
      patella and lower clinical outcomes. In light of these results, routine patellar
      resurfacing as part of a primary TKA might be reevaluated. SPECT/CT enables a
      precise localization of the BTU and might be considered as the ideal imaging
      modality for evaluation and investigate of patellofemoral disorders after TKA.

PMID- 29188335
TI  - Poly-traumatic multi-ligament knee injuries: is the knee the limiting factor?
AB  - PURPOSE: Multi-ligament knee injuries (MLKI) from a high-velocity accident are
      rare but potentially devastating. This matched cohort analysis compares knee
      functional outcomes after multiple ligament reconstruction in poly-trauma
      patients to those that occurred in isolation. METHODS: Sixty-two patients with
      MLKI that occurred either as a component of polytrauma or had occurred in
      isolation were matched according to age, sex, and knee dislocation grade.
      Functional outcomes and knee physical examination were assessed at a 2-year
      follow-up. New Injury Severity Score (NISS) was calculated based on the poly
      traumatic injury pattern. Risk factors for worse outcomes in the poly-trauma
      cohort were analyzed. RESULTS: The mean IKDC, Lysholm, and NISS scores in the
      polytrauma cohort were 57.2 +/- 21.9, 62 +/- 22, and 40.9 +/- 20.4, respectively,
      at a mean of 67 months (range 24-220). The isolated knee injury group was
      followed for a mean of 74 months (range 24-266) with mean IKDC and Lysholm scores
      of 71.1 +/- 26.5 and 78 +/- 23, respectively. Patients in the control cohort had
      significantly higher IKDC (p = 0.01) and Lysholm scores, (p = 0.003). There were
      no major differences between the two groups in regards physical examination
      findings at final follow-up. None of the analyzed risk factors was predictive of
      poor outcome. CONCLUSION: When comparing knees with similar multi-ligament and
      neurovascular injury patterns, patients who sustained their injury as a result of
      poly-trauma demonstrated significantly lower functional scores following
      reconstruction. This is despite restoration of similar knee stability and range
      of motion. The functional outcomes following MLKI reconstruction in poly
      traumatized patients are influenced by factors other than the knee including
      concomitant injuries and psychosocial factors. LEVEL OF EVIDENCE: Therapeutic
      Level III.

PMID- 29188336
TI  - No risk of arthrofibrosis after acute anterior cruciate ligament reconstruction.
AB  - PURPOSE: To compare acute ACL reconstruction (ACLR) within 8 days of injury with
      delayed reconstruction after normalized range of motion (ROM), 6-10 weeks after
      injury. It was hypothesized that acute ACL reconstruction with modern techniques
      is safe and can be beneficial in terms of patient-reported outcomes and range of
      motion. METHODS: Sample size calculation indicated 64 patients would be required
      to find a 5 degrees  difference in ROM at 3 months. Seventy patients with high
      recreational activity level, Tegner level 6 or more, were randomized to acute
      (within 8 days) or delayed (6-10 weeks) ACLR between 2006 and 2013. During the
      first 3 months following surgery patients were contacted weekly by SMS and asked
      'How is your knee functioning?', with answers given on a Visual-Analog Scale (0
      10). ROM was assessed after 3 months by the rehab physiotherapist. Patient
      reported outcomes, objective IKDC and manual stability measurements were
      collected by an independent physiotherapist not involved in the rehab at the 6
      month follow-up. RESULTS: At 3-month follow-up, 91% of the patients were assessed
      with no significant differences in flexion, extension or total ROM demonstrated
      between groups. At the 6-month follow-up, the acute group had significantly less
      muscle atrophy of the thigh muscle compared to the contralateral leg.
      Furthermore, a significantly higher proportion of patients in the acute group
      passed or were close to passing the one leg hop test (47 versus 21%, p = 0.009).
      No difference was found between the groups in the other clinical assessments.
      Additionally, no significant difference between the groups was found in terms of
      associated injuries. CONCLUSION: Acute ACLR within 8 days of injury does not
      appear to adversely affect ROM or result in increased stiffness in the knee joint
      when compared to delayed surgery. LEVEL OF EVIDENCE: II.

PMID- 29188337
TI  - Correction to: Increased plasma N-glycome complexity is associated with higher
      risk of type 2 diabetes.
AB  - The authors regret that Nish Chaturvedi's name was spelt incorrectly in the
      author list. The details given in this correction are correct.

PMID- 29188338
TI  - Effects of hypoglycaemia on working memory and regional cerebral blood flow in
      type 1 diabetes: a randomised, crossover trial.
AB  - AIMS/HYPOTHESIS: The aim of this randomised, crossover trial was to compare
      cognitive functioning and associated brain activation patterns during
      hypoglycaemia (plasma glucose [PG] just below 3.1 mmol/l) and euglycaemia in
      individuals with type 1 diabetes mellitus. METHODS: In this patient-blinded,
      crossover study, 26 participants with type 1 diabetes mellitus attended two
      randomised experimental visits: one hypoglycaemic clamp (PG 2.8 +/- 0.2 mmol/l,
      approximate duration 55 min) and one euglycaemic clamp (PG 5.5 mmol/l +/- 10%).
      PG levels were maintained by hyperinsulinaemic glucose clamping. Cognitive
      functioning was assessed during hypoglycaemia and euglycaemia conditions using a
      modified version of the digit symbol substitution test (mDSST) and control DSST
      (cDSST). Simultaneously, regional cerebral blood flow (rCBF) was measured in pre
      specified brain regions by six H215O-positron emission tomographies (PET) per
      session. RESULTS: Working memory was impaired during hypoglycaemia as indicated
      by a statistically significantly lower mDSST score (estimated treatment
      difference [ETD] -0.63 [95% CI -1.13, -0.14], p = 0.014) and a statistically
      significantly longer response time (ETD 2.86 s [7%] [95% CI 0.67, 5.05], p =
      0.013) compared with euglycaemia. During hypoglycaemia, mDSST task performance
      was associated with increased activity in the frontal lobe regions, superior
      parietal lobe and thalamus, and decreased activity in the temporal lobe regions
      (p < 0.05). Working memory activation (mDSST - cDSST) statistically significantly
      increased blood flow in the striatum during hypoglycaemia (ETD 0.0374% [95% CI
      0.0157, 0.0590], p = 0.002). CONCLUSIONS/INTERPRETATION: During hypoglycaemia
      (mean PG 2.9 mmol/l), working memory performance was impaired. Altered
      performance was associated with significantly increased blood flow in the
      striatum, a part of the basal ganglia implicated in regulating motor functions,
      memory, language and emotion. TRIAL REGISTRATION: NCT01789593, clinicaltrials.gov
      FUNDING: This study was funded by Novo Nordisk.

PMID- 29188340
TI  - ?

PMID- 29188341
TI  - A review of metabolic potential of human gut microbiome in human nutrition.
AB  - The human gut contains a plethora of microbes, providing a platform for metabolic
      interaction between the host and microbiota. Metabolites produced by the gut
      microbiota act as a link between gut microbiota and its host. These metabolites
      act as messengers having the capacity to alter the gut microbiota. Recent
      advances in the characterization of the gut microbiota and its symbiotic
      relationship with the host have provided a platform to decode metabolic
      interactions. The human gut microbiota, a crucial component for dietary
      metabolism, is shaped by the genetic, epigenetic and dietary factors. The
      metabolic potential of gut microbiota explains its significance in host health
      and diseases. The knowledge of interactions between microbiota and host
      metabolism, as well as modification of microbial ecology, is really beneficial to
      have effective therapeutic treatments for many diet-related diseases in near
      future. This review cumulates the information to map the role of human gut
      microbiota in dietary component metabolism, the role of gut microbes derived
      metabolites in human health and host-microbe metabolic interactions in health and
      diseases.

PMID- 29188339
TI  - Clinical and metabolic features of the randomised controlled Diabetes Remission
      Clinical Trial (DiRECT) cohort.
AB  - AIMS/HYPOTHESIS: Substantial weight loss in type 2 diabetes can achieve a return
      to non-diabetic biochemical status, without the need for medication. The Diabetes
      Remission Clinical Trial (DiRECT), a cluster-randomised controlled trial, is
      testing a structured intervention designed to achieve and sustain this over 2
      years in a primary care setting to determine practicability for routine clinical
      practice. This paper reports the characteristics of the baseline cohort. METHODS:
      People with type 2 diabetes for <6 years with a BMI of 27-45 kg/m2 were recruited
      in 49 UK primary care practices, randomised to either best-practice diabetes care
      alone or with an additional evidence-based weight management programme
      (Counterweight-Plus). The co-primary outcomes, at 12 months, are weight loss >=15
      kg and diabetes remission (HbA1c <48 mmol/mol [6.5%]) without glucose-lowering
      therapy for at least 2 months. Outcome assessors are blinded to group assignment.
      RESULTS: Of 1510 people invited, 423 (28%) accepted; of whom, 306 (72%) were
      eligible at screening and gave informed consent. Seven participants were later
      found to have been randomised in error and one withdrew consent, leaving 298 (176
      men, 122 women) who will form the intention to treat (ITT) population for
      analysis. Mean (SD) age was 54.4 (7.6) years, duration of diabetes 3.0 (1.7)
      years, BMI 34.6 (4.4) kg/m2 for all participants (34.2 (4.2) kg/m2 in men and
      35.3 (4.6) kg/m2 in women) and baseline HbA1c (on treatment) 59.3 (12.7) mmol/mol
      (7.6% [1.2%]). The recruitment rate in the intervention and control groups, and
      comparisons between the subgroups recruited in Scotland and England, showed few
      differences. CONCLUSIONS/INTERPRETATION: DiRECT has recruited a cohort of people
      with type 2 diabetes with characteristics similar to those seen in routine
      practice, indicating potential widespread applicability. Over 25% of the eligible
      population wished to participate in the study, including a high proportion of
      men, in line with the prevalence distribution of type 2 diabetes. TRIAL
      REGISTRATION: www.controlled-trials.com/ISRCTN03267836 ; date of registration 20
      December 2013.

PMID- 29188342
TI  - Spirosoma jeollabukense sp. nov., isolated from soil.
AB  - A Gram-negative, non-motile, rod-shaped, aerobic bacterial strain, designated S2
      3-6T, was isolated from soil in Jeollabuk-do province, South Korea, and was
      characterized taxonomically using a polyphasic approach. According to a
      comparative 16S rRNA gene sequence analysis, strain S2-3-6T belonged to the
      family Cytophagaceae and was most closely related to Spirosoma endophyticum EX36T
      (98.2%), Spirosoma fluviale MSd3T (96.0%), and Spirosoma linguale DSM 74T
      (95.7%). Strain S2-3-6T contained summed feature 3 (C16:1 omega7c/C16:1 omega6c),
      C16:1 omega5c, and C16:0 N alcohol as major cellular fatty acids, MK-7 as the
      predominant respiratory quinone, and phosphatidylethanolamine as the main polar
      lipid. The DNA G+C content of strain S2-3-6T was 47.8%. Phenotypic and
      chemotaxonomic data supported the affiliation of strain S2-3-6T to the genus
      Spirosoma. However, the DNA-DNA relatedness between strain S2-3-6T and Spirosoma
      endophyticum KACC 17920T was 27%, clearly showing that the isolate constitutes a
      new genospecies. Strain S2-3-6T could be clearly differentiated from its closest
      neighbors based on its phenotypic, genotypic, and chemotaxonomic features.
      Therefore, strain S2-3-6T represents a novel species of the genus Spirosoma, for
      which the name Spirosoma jeollabukense sp. nov. is proposed. The type strain is
      S2-3-6T (= KCTC 52725T = JCM 32129T).

PMID- 29188343
TI  - Lysobacter tongrenensis sp. nov., isolated from soil of a manganese factory.
AB  - A Gram-staining negative, aerobic, non-motile, rod-shaped bacterial strain,
      designated YS-37T, was isolated from soil in a manganese factory, People's
      Republic of China. Based on16S rRNA gene sequence analysis, strain YS-37T was
      most closely related to Lysobacter pocheonensis Gsoil 193T (97.0%), Lysobacter
      dokdonensis DS-58T (96.0%) and Lysobacter daecheongensis Dae08T (95.8%) and
      grouped together with L. pocheonensis Gsoil 193T and Lysobacter dokdonensis DS
      58T. The DNA-DNA hybridization value between strain YS-37T and L. pocheonensis
      KCTC 12624T was 43.3% (+/- 1). The major respiratory quinone of strain YS-37T was
      ubiquinone-8, and the polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol, phospholipid,
      phosphatidylmethylethaolamine and two unknown lipids. Its major cellular fatty
      acids (> 5%) were iso-C15:0, iso-C17:1 omega9c, iso-C16:0, iso-C11:0 3-OH and iso
      C11:0 and the G + C content of the genomic DNA was 67.1 mol%. Strain YS-37T also
      showed some biophysical and biochemical differences with the related strains,
      especially in hydrolysis of casein. The results demonstrated that strain YS-37T
      belongs to genus Lysobacter and represents a novel Lysobacter species for which
      the name Lysobacter tongrenensis sp. nov. is proposed. The type strain is YS-37T
      (= CCTCC AB 2016052T = KCTC 52206T).

PMID- 29188344
TI  - Citreibacter salsisoli gen. nov., sp. nov., a bacterium isolated from marine
      soil.
AB  - A Gram-stain-negative, strictly aerobic, yellow-colored, rod-shaped,
      chemoheterotrophic bacterium, designated SNA426T, was isolated from marine soil
      in the Republic of Korea. Preliminary analysis based on the 16S rRNA gene
      sequence revealed that the novel marine isolate was affiliated with the family
      Flavobacteriaceae of phylum Bacteroidetes and that it shared the highest (96.2%)
      sequence similarity with Gillisia mitskevichiae KMM 6034T. The strain could be
      differentiated phenotypically from related members of the family
      Flavobacteriaceae. The major fatty acids of strain SNA426T were iso-C15:0, C16:1
      omega7c and/or C16:1 omega6c and iso-C17:0 3-OH. The DNA G+C content of the
      strain was 39.6 mol% and the major respiratory quinone was menaquinone 6 (MK-6).
      Strain SNA426T had phosphatidylethanolamine, phosphatidylcholine, three
      unidentified aminolipids and nine unidentified lipids as polar lipids. From the
      distinct phylogenetic position and combination of genotypic and phenotypic
      characteristics, the strain is considered to represent a novel genus in the
      family Flavobacteriaceae, for which the name Citreibacter gen. nov. is proposed.
      The type species is Citreibacter salsisoli sp. nov., with the type strain SNA426T
      (= KCCM 90269T = CGMCC 1.16129T).

PMID- 29188346
TI  - [Diagnosis, treatment and follow-up of testicular cancer].
AB  - BACKGROUND: Testicular cancer is a disease of young adult men, and it is curable
      in most cases. Even in advanced disease, cure rates reach 80 % nowadays. This was
      achieved by consistently performing studies concerning the different stages of
      disease. TREATMENT AND FOLLOW-UP CARE: The concept of treatment is
      interdisciplinary. After removal of the affected testis, histology and stage
      determine further therapy, which can be active surveillance, polychemotherapy,
      radiotherapy, surgery, or a combination of these. Curability also has
      consequences for the long-term follow-up. We speak about long-term survivorship.
      Besides looking for recurrences, it is also necessary to observe and treat long
      term toxicities caused by the different therapeutic procedures. CONCLUSION:
      Because testicular cancer is rare with about 4500 cases annually, treatment
      especially for advanced disease-should be performed at centers. In addition, it
      is possible to obtain a second opinion using the Interdisciplinary German
      Testicular Study Group website.

PMID- 29188347
TI  - [From boxing to geriatric psychiatry : Facets from the work of East German social
      psychiatrist Bernhard Schwarz (1918-1991)].
AB  - For the first time, this study presents publications representative for the work
      of the neurologist and sports physician Bernhard Schwarz, whose career spans from
      the 1950s to the 1970s. His work is characterized by exceptional originality.
      Schwarz acted as the physician of the GDR national boxing team and conducted a
      systematic long-term study of 800 boxers. He found increased occurrences of
      depression, Alzheimer's and Parkinson's diseases and suggested that these were
      linked to recurring craniocerebral injury. He was concerned about avoiding such
      long-term health effects in boxers and suggested a range of preventive measures
      that were later reflected in the guidelines of international boxing associations.
      Schwarz was distinguished by his drive to directly implement social psychiatric
      approaches in the hospital. As head of the psychiatric clinic at Leipzig
      University, he initiated a club for geriatric patients to help older patients
      with the problematic transition from hospitalization to outpatient assistance at
      home. Influenced by holistic anthropological thinking, he regarded geriatric
      mental illness as a consequence of social isolation. In addition, Schwarz was
      involved in a model project that assessed the work resilience of patients in the
      hospital with the goal of optimizing psychiatric rehabilitation. Both projects
      were successes, according to his published accounts.

PMID- 29188345
TI  - Imaging in syndesmotic injury: a systematic literature review.
AB  - OBJECTIVES: To give a systematic overview of current diagnostic imaging options
      for assessment of the distal tibio-fibular syndesmosis. MATERIALS AND METHODS: A
      systematic literature search across the following sources was performed: PubMed,
      ScienceDirect, Google Scholar, and SpringerLink. Forty-two articles were included
      and subdivided into three groups: group one consists of studies using
      conventional radiographs (22 articles), group two includes studies using computed
      tomography (CT) scans (15 articles), and group three comprises studies using
      magnet resonance imaging (MRI, 9 articles).The following data were extracted:
      imaging modality, measurement method, number of participants and ankles included,
      average age of participants, sensitivity, specificity, and accuracy of the
      measurement technique. The Quality Assessment of Diagnostic Accuracy Studies 2
      (QUADAS-2) tool was used to assess the methodological quality. RESULTS: The three
      most common techniques used for assessment of the syndesmosis in conventional
      radiographs are the tibio-fibular clear space (TFCS), the tibio-fibular overlap
      (TFO), and the medial clear space (MCS). Regarding CT scans, the tibio-fibular
      width (axial images) was most commonly used. Most of the MRI studies used direct
      assessment of syndesmotic integrity. Overall, the included studies show low
      probability of bias and are applicable in daily practice. CONCLUSIONS:
      Conventional radiographs cannot predict syndesmotic injuries reliably. CT scans
      outperform plain radiographs in detecting syndesmotic mal-reduction.
      Additionally, the syndesmotic interval can be assessed in greater detail by CT.
      MRI measurements achieve a sensitivity and specificity of nearly 100%; however,
      correlating MRI findings with patients' complaints is difficult, and utility with
      subtle syndesmotic instability needs further investigation. Overall, the
      methodological quality of these studies was satisfactory.

PMID- 29188348
TI  - [Big data approaches in psychiatry: examples in depression research].
AB  - BACKGROUND: The exploration and therapy of depression is aggravated by
      heterogeneous etiological mechanisms and various comorbidities. With the growing
      trend towards big data in psychiatry, research and therapy can increasingly
      target the individual patient. This novel objective requires special methods of
      analysis. OBJECTIVE: The possibilities and challenges of the application of big
      data approaches in depression are examined in closer detail. MATERIAL AND
      METHODS: Examples are given to illustrate the possibilities of big data
      approaches in depression research. Modern machine learning methods are compared
      to traditional statistical methods in terms of their potential in applications to
      depression. RESULTS: Big data approaches are particularly suited to the analysis
      of detailed observational data, the prediction of single data points or several
      clinical variables and the identification of endophenotypes. A current challenge
      lies in the transfer of results into the clinical treatment of patients with
      depression. CONCLUSION: Big data approaches enable biological subtypes in
      depression to be identified and predictions in individual patients to be made.
      They have enormous potential for prevention, early diagnosis, treatment choice
      and prognosis of depression as well as for treatment development.

PMID- 29188349
TI  - ["Understanding" in psychiatry -Part 2 : From incomprehensibility to an attitude
      of participative communication].
AB  - BACKGROUND: Starting from a systematic research of "incomprehensibility" we
      propose a turn from an epistemological analysis of "to understand" to an
      anthropological perspective relying on participative communication in a shared
      space of resonance. METHOD: We propose a systematization of the modes of
      understanding and of incomprehensibility based on a two-dimensional model
      combining epistemological and ontological perspectives. Finally, we outline
      "understanding" as a medical stance related to the healing relationship, which
      implies a disposition to get involved in a participative communication. We put
      forward the hypothesis that acceptance of the otherness of the patient, without
      the intention of a complete appropriation of meaning, could be noted as crucial
      feature of the anthropological approach. RESULTS: In clinical medicine,
      especially in psychiatry, "not understood" is threefold: as "misunderstanding",
      as "not-understanding" (as a temporary lack of understanding), and as
      incomprehensibility (to understand, that there is nothing to be understood).
      Incomprehensibility may only allow for interpretative operations up to a certain
      limit. This unidirectional understanding as a diagnosing subsumption or as a
      psychological explanation in order to grasp meanings has to be completed by a bi
      directional personal approach based on an engaging attitude (dialogical as well
      as quiescent) while acknowledging the incomprehensible. DISCUSSION: A second
      person-perspective emphasizes the healing relationship as an existential
      encounter, especially in personal liminal situations for the patient. From an
      anthropological perspective "to understand" has not only to be grasped as a
      semantic agreement, but also as an attitude towards participative communication.
      That means a disposition to get involved in the encounter with the mentally ill
      without aiming for grasping rationally significances or even to attribute
      meanings. The stance therefore should be based on an awareness for the patient's
      idiosyncrasy as well as on the empathetic production of a shared space of
      resonance within the healing relationship.

PMID- 29188350
TI  - ["Understanding" in psychiatry-part 1 : Philosophical sources and concept
      analysis].
AB  - BACKGROUND: The dichotomy comprehension/understanding vs. explanation has been
      initially developed with a legitimating intention for the humanities vis a vis
      the natural sciences. This investigation examines the different usages of
      understanding/comprehension in psychiatry and psychotherapy as well as its
      relevance for medical practice. METHOD: Critical discussion of the historical
      roots of the comprehension-explanation dichotomy and its introduction into the
      psychiatry by Jaspers. A propaedeutic logical analysis of the concept of
      "understanding" will be proposed. This investigation aims to elucidate latent
      dimensions in the usage of "understanding" in psychiatry and psychotherapy. In
      more detail the operation of assignment and attribution will be discussed as well
      as the elucidation of individual meaning and supraindividual significance.
      RESULTS: The term analysis shows that "to understand" as a predicate is gradually
      and polysemic; its definition must take the different logically additive meanings
      into account. These meanings can be condensed into three dimensions: i. Rational
      diagnostic assignment; ii. Elucidation of meaning through individual empathetic
      re-experiencing as a psychological approach respectively the supraindividual
      elucidation of significance, and; iii. Dialogic attitude. Psychological
      understanding roots in Jaspers' epistemology on assignment to and alignment with
      supraindividual meaningful connections and not on empathetic re-experiencing.
      DISCUSSION: "To understand" as a logical operation of assignment and as meaning
      elucidation takes for granted a predicate in its transitive first-person
      perspective ("who" should be understood, as objectified) in conjunction to a
      third-person perspective ("what" should be understood). This analysis should be
      complemented by a first-person perspective ("who" should be understood, as a
      subject) in conjunction with a dialogic second-person perspective ("how" should
      be understood, following a mutual disposition). This last approach will be
      discussed in an additional article.

PMID- 29188351
TI  - [Chronic course of neurosyphilis].

PMID- 29188352
TI  - [Prospective DRG coding : Improvement in cost-effectiveness and documentation
      quality of in-patient hospital care].
AB  - BACKGROUND: In prospective reimbursement schemes a diagnosis-related group (DRG)
      is assigned to each case according to all coded diagnoses and procedures. This
      process can be conducted retrospectively after (DC) or prospectively during the
      hospitalization (PC). The use of PC offers advantages in terms of cost
      effectiveness and documentation quality without impairing patient safety.
      MATERIAL AND METHODS: A retrospective analysis including all DRG records and
      billing data from 2012 to 2015 of a surgical department was carried out. The use
      of PC was introduced into the vascular surgery unit (VS) in September 2013, while
      the remaining surgical units (RS) stayed with DC. Analysis focused on differences
      between VS and RS before and after introduction of PC. Characteristics of cost
      effectiveness were earnings (EBIT-DA), length of stay (LOS), the case mix index
      (CMI) and the productivity in relation to the DRG benchmark (productivity index,
      PI). The number of recorded diagnoses/procedures (ND/NP) was an indicator for
      documentation quality. RESULTS: A total of 1703 cases with VS and 27,679 cases
      with RS were analyzed. After introduction of PC the EBIT-DA per case increased in
      VS but not in RS (+3342 Swiss francs vs. +84, respectively, p < 0.001). The CMI
      increased slightly in both groups (+0.10 VS vs. +0.08 RS, p > 0.05) and the LOS
      was more reduced in VS than in RS (-0.36 days vs. -0.03 days, p > 0.005). The PI
      increased in VS but decreased in RS (+0.131 vs. -0.032, p < 0.001), ND increased
      more in VS (+1.29 VS vs. +0.26 RS, p < 0.001) and NP remained stable in both
      groups. CONCLUSION: The use of PC helps to significantly improve cost
      effectiveness and documentation quality of in-patient hospital care, essentially
      by optimizing LOS and cost weight in relation to the DRG benchmark, i. e.
      increasing the PI. The increasing ND indicates an improvement in documentation
      quality.

PMID- 29188353
TI  - [Quality indicators for surgery of rectal cancer : Evidence-based development of
      a set of indicators for quality].
AB  - The definition of valid quality indicators is an essential task of medical self
      administration and quality assurance. Based on the literature and the results of
      the Study, Documentation, and Quality Center (StuDoQ) Rectal Cancer Registry, we
      suggest the following QIs: rate of circumferential resection margin (CRM)
      positive resected material, rate of anastomotic leak in patients with
      anastomoses, rate of abdominal wound healing disorders and rate of patients with
      newly established permanent urinary diversion. Additionally, a new marker, the
      MTL30, which subsumes patient death within 30 days after the index operation,
      patient transfer to another acute hospital within 30 days after the index
      operation or a length of inpatient hospital stay of more than 30 days.

PMID- 29188354
TI  - [Endoscopic techniques for early stage cancer of the upper and lower
      gastrointestinal tract : Possibilities and limitations].
AB  - BACKGROUND: Endoscopic resection (ER) provides a minimally invasive treatment
      option for early gastrointestinal cancers. OBJECTIVE: Presentation of current
      guideline recommendations. Presentation and discussion of published data
      regarding ER of early esophageal cancer, early gastric cancer and early
      colorectal cancer. MATERIAL AND METHODS: Analysis of the current literature.
      Presentation of endoscopic case reports. RESULTS: New technologies, e. g. narrow
      band imaging (NBI) have improved the endoscopic diagnosis of early
      gastrointestinal neoplasms. The development of endoscopic submucosal dissection
      (ESD) allowed higher R0 resection rates and minimized the recurrence risk leading
      to higher rates of curative endoscopic resection. Resection criteria are defined
      in national and international guidelines. Resection criteria for early gastric
      cancer are different between German (guideline criteria) and Asian guidelines
      (expanded criteria). New German data did not show a difference in long-term
      survival after ESD of early gastric cancers fulfilling the guideline criteria or
      the expanded criteria. In early colorectal cancer submucosal invasion exceeding
      1000 um is defined as the limit for ER in current guidelines. This threshold
      might be too strict for subgroups without further risk factors but further data
      are awaited. CONCLUSION: Substantial progress has been made in endoscopic
      diagnostics and treatment of early gastrointestinal cancers. First European data
      could confirm previous Asian results; however, further studies are urgently
      needed for a better definition of the possibilities and limitations of ER.

PMID- 29188355
TI  - [Resection concepts for early stage neuroendocrine tumors of the lungs and
      bronchi].
AB  - BACKGROUND: Neuroendocrine tumors of the lungs are a very inhomogeneous group of
      malignancies. The surgical treatment should be adapted to the anatomical
      localization and histological subtype and individualized according to the
      functional reserve. MATERIAL AND METHODS: We performed a selective review of
      current literature, which was supplemented by personal experiences. RESULTS: The
      currently available outcome data are very inhomogeneous and depend on the
      histological subtype of neuroendocrine pulmonary tumors. A radical R0 resection
      is the key for an improvement in long-term overall and disease-free survival.
      CONCLUSION: Surgical treatment of carcinoid tumors is the current standard
      therapy. Sleeve resection should be performed, whenever possible. More aggressive
      tumors, such as large cell neuroendocrine carcinoma and small cell lung cancer
      should be treated in a multimodal concept.

PMID- 29188356
TI  - [Antihypertensive therapy in the elderly].
AB  - Arterial hypertension is the most common modifiable risk factor for
      cerebrovascular and cardiovascular morbidity and mortality in old age. The
      prevention of cognitive brain disorders is also a therapeutic goal of long-term
      treatment of hypertension. Older patients also have a higher risk of developing
      cardiovascular diseases and therefore benefit from a relatively moderate
      reduction in blood pressure. With respect to the high prevalence of hypertension
      in old age and the increasing incidence with time, the therapy of hypertension is
      becoming increasingly more important to achieve an improved prognosis for
      patients along with a reduction of costs. The accurate blood pressure measurement
      for elderly patients includes repeated measurements while standing and sitting.
      Additionally, the measurements should also be conducted by the patient or by a
      family member. The most accurate method for assessing the daily blood pressure
      level, e.g. practice hypertension, non-dipping and intermittent hypertension, is
      the 24-h blood pressure measurement by ambulatory blood pressure monitoring
      (ABPM). General measures and lifestyle interventions are effective for reducing
      blood pressure of elderly patients with hypertension and a low salt diet is
      scientifically proven to be superior. The same drugs used for young people are
      also recommended for older patients and most give preference to diuretics, renin
      angiotensin-aldosterone system (RAAS) inhibitors and calcium antagonists. The
      target blood pressure in elderly patients is repeatedly the focus of scientific
      discussions. The current recommendations are presented in the text and the
      characteristics which must be particularly considered in the therapy of elderly
      patients are presented in detail.

PMID- 29188357
TI  - [Management of valvular heart disease : ESC/EACTS guidelines 2017].
AB  - After 5 years the European Society of Cardiology and the European Association for
      Cardio-Thoracic Surgery have released an update on the guidelines for the
      management of valvular heart diseases. In recent years published results of
      randomized trials in patients with aortic valve stenosis have resulted in updated
      recommendations for catheter-based prosthesis implantation (TAVI), which is now
      extended to patients presenting without a low risk for conventional surgical
      valve replacement. In mitral or tricuspid valvular disease, the recommendations
      for catheter-based therapies are less strong because of a lack of supportive
      scientific data. A special focus of these updated guidelines is on concomitant
      antithrombotic therapy in valvular heart disease and in the context of a
      combination with coronary artery disease and/or accompanying arrhythmia. Special
      emphasis was again put on the multidisciplinary heart team for the diagnostics
      and treatment of patients with valvular heart disease. In order to support the
      quality of treatment for patients with valvular heart disease, it is suggested
      that heart valve centers of excellence should be established, which have to
      fulfil complex personnel, structural and technological prerequisites.

PMID- 29188358
TI  - Anticoagulation strategies in patients with atrial fibrillation after PCI or with
      ACS : The end of triple therapy?
AB  - Clinicians struggle daily with the optimal regimen for patients with an
      indication for antiplatelet therapy after stenting and in patients needing oral
      anticoagulation treatment for atrial fibrillation (AF). This is not only
      difficult in patients with acute coronary syndrome (ACS) but also in the large
      number of patients with AF undergoing elective percutaneous coronary intervention
      (PCI). The challenge is to strike a balance between the increasing risk of
      bleeding events and ischemic or thrombotic events. Until recently, guidelines
      were based on expert consensus and a few small, many of them retrospective,
      trials. A so-called triple therapy with a vitamin K antagonist (VKA) and dual
      antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended for
      patients with AF undergoing PCI in stable coronary artery disease or for those
      with ACS. However, severe bleeding complications remain a major issue during
      triple therapy, particularly in the growing aging population. In the past year,
      randomized controlled trials (RCT) with direct-acting oral anticoagulants (DOACs)
      have modified the standard use of care, now favoring dual therapy with DOACs.
      This review elucidates the current influential RCTs on the new antiplatelet and
      anticoagulation strategies for patients with AF undergoing PCI or with ACS, and
      discusses whether triple therapy is still required.

PMID- 29188359
TI  - Biosynthesis of gold nanoparticles using cell-free extracts of Magnusiomyces
      ingens LH-F1 for nitrophenols reduction.
AB  - A green and eco-friendly method for the synthesis of gold nanoparticles (AuNPs)
      was developed using the cell-free extracts of a yeast strain Magnusiomyces ingens
      LH-F1. UV-vis spectra showed a distinct absorption band at ~ 540 nm,
      corresponding to the surface plasmon resonance of AuNPs. Transmission electron
      microscopy images revealed that the shapes of AuNPs were almost spherical and
      pseudo-spherical. Fourier transform infrared spectroscopy and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analyses suggested that some proteins
      containing amino- and carboxyl-groups in the cell-free extracts were absorbed on
      the surface of nanoparticles, which could act as reducing and capping agents for
      AuNPs synthesis. Furthermore, with the concentration of cell-free extracts
      increasing from 25 to 200 mg L-1, the average size of AuNPs decreased from 28.3
      to 20.3 nm. Meanwhile, the morphology became more uniform with less irregular
      shapes. In addition, the as-synthesized AuNPs showed an excellent catalytic
      activity for nitrophenols reduction (i.e., 4-nitrophenol, 3-nitrophenol and 2
      nitrophenol) in the presence of excess NaBH4. The catalytic rate constant of
      nitrophenols reduction was also dependent on cell-free extract concentration. The
      larger AuNPs synthesized by less cell-free extracts were covered with a thinner
      corona and showed better capacity for reducing nitrophenols. This study suggested
      that the as-synthesized AuNPs could be employed as efficient catalysts in
      reduction of organic contaminants.

PMID- 29188360
TI  - HANP on renal damage during cardiac surgery.

PMID- 29188361
TI  - Disruptive technological advances in vascular access for dialysis: an overview.
AB  - End-stage kidney disease (ESKD), one of the most prevalent diseases in the world
      and with increasing incidence, is associated with significant morbidity and
      mortality. Current available modes of renal replacement therapy (RRT) include
      dialysis and renal transplantation. Though renal transplantation is the preferred
      and ideal mode of RRT, this modality may not be available to all patients with
      ESKD. Moreover, renal transplant recipients are constantly at risk of
      complications associated with immunosuppression and immunosuppressant use, and
      posttransplant lymphoproliferative disorder. Dialysis may be the only available
      modality in certain patients. However, dialysis has its limitations, which
      include issues associated with lack of vascular access, risks of infections and
      vascular thrombosis, decreased quality of life, and absence of biosynthetic
      functions of the kidney. In particular, the creation and maintenance of
      hemodialysis vascular access in children poses a unique set of challenges to the
      pediatric nephrologist owing to the smaller vessel diameters and vascular
      hyperreactivity compared with adult patients. Vascular access issues continue to
      be one of the major limiting factors prohibiting the delivery of adequate
      dialysis in ESKD patients and is the Achilles' heel of hemodialysis. This review
      aims to provide a critical overview of disruptive technological advances and
      innovations for vascular access. Novel strategies in preventing neointimal
      hyperplasia, novel bioengineered products, grafts and devices for vascular access
      will be discussed. The potential impact of these solutions on improving the
      morbidity encountered by dialysis patients will also be examined.

PMID- 29188363
TI  - Meta-analysis of adjunctive dexamethasone to improve clinical outcome of
      bacterial meningitis in children.
AB  - BACKGROUND: The current recommended therapies for bacterial meningitis are
      effective antimicrobial agents and the implementation of childhood vaccination
      programs. However, the role of adjunctive dexamethasone therapy in bacterial
      meningitis remains controversial. METHODS: Using meta-analysis, this study aims
      to investigate the efficacy of adjunctive dexamethasone therapy in bacterial
      meningitis by comparing it with antibiotic therapy. Documents of randomized
      controlled trials (RCT) related to the treatment of bacterial meningitis in
      children with dexamethasone published since the establishment of the databases to
      December in 2016 were retrieved from the databases of Cochrane Library, Pubmed,
      MEDLINE, EMBASE, Chinese BioMedical Literature Database, and China National
      Knowledge Infrastructure. The references in RCT were retrieved by hands at the
      same time. Full texts of screened documents were searched and given qualitative
      review, and then, all RCT included were analyzed statistically by using Review
      Manger 5.3 software. RESULTS: The search yielded 15 studies (2409 children
      cases), among which 4 fall in grade A and 11 were grade B. The results of meta
      analysis have shown that patients who received dexamethasone have significantly
      lower risks in incidence of hearing loss (OR = 0.68, 95%CI 0.53-0.89, P = 0.004)
      and severe neurological sequelae (OR = 0.59, 95%CI 0.37-0.95, P = 0.03), but the
      follow-up mortality is hardly effected (OR = 0.86, 95%CI 0.67-1.10, P = 0.23).
      CONCLUSIONS: Evidence has proven that the adjunctive administration of
      dexamethasone is conducive to treating children with bacterial meningitis to a
      certain extent, to decreasing the possibility of hearing loss and severe
      neurological sequelae, but has no significant effect on the follow-up mortality.

PMID- 29188362
TI  - The NF-kappaB signalling pathway in colorectal cancer: associations between
      dysregulated gene and miRNA expression.
AB  - BACKGROUND: The nuclear factor-kappa B (NF-kappaB) signalling pathway is a
      regulator of immune response and inflammation that has been implicated in the
      carcinogenic process. We examined differentially expressed genes in this pathway
      and miRNAs to determine associations with colorectal cancer (CRC). METHODS: We
      used data from 217 CRC cases to evaluate differences in NF-kappaB signalling
      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
      analysed. We evaluated genes most strongly associated and differentially
      expressed (fold change (FC) of > 1.5 or < 0.67) that were statistically
      significant after adjustment for multiple comparisons. RESULTS: Of the 92 genes
      evaluated, 22 were significantly downregulated and nine genes were significantly
      upregulated in all tumours. Two additional genes (CD14 and CSNK2A1) were
      dysregulated in MSS tumours and two genes (CARD11 and VCAM1) were downregulated
      and six genes were upregulated (LYN, TICAM2, ICAM1, IL1B, CCL4 and PTGS2) in MSI
      tumours. Sixteen of the 21 dysregulated genes were associated with 40 miRNAs.
      There were 76 miRNA:mRNA associations of which 38 had seed-region matches. Genes
      were associated with multiple miRNAs, with TNFSRF11A (RANK) being associated with
      15 miRNAs. Likewise several miRNAs were associated with multiple genes (miR-150
      5p with eight genes, miR-195-5p with four genes, miR-203a with five genes, miR
      20b-5p with four genes, miR-650 with six genes and miR-92a-3p with five genes).
      CONCLUSIONS: Focusing on the genes and their associated miRNAs within the entire
      signalling pathway provides a comprehensive understanding of this complex pathway
      as it relates to CRC and offers insight into potential therapeutic agents.

PMID- 29188364
TI  - Complete genome sequence of Paris mosaic necrosis virus, a distinct member of the
      genus Potyvirus.
AB  - The complete genomic sequence of a novel potyvirus was determined from Paris
      polyphylla var. yunnanensis. Its genomic RNA consists of 9,660 nucleotides (nt)
      excluding the 3'-terminal poly (A) tail, containing the typical open reading
      frame (ORF) of potyviruses and encoding a putative large polyprotein of 3030
      amino acids. The virus shares 53.9-70.1% nt sequence identity and 43.9-73.2%
      amino acid sequence identity with other viruses classified within the genus
      Potyvirus. Proteolytic cleavage sites and conserved motifs of the potyviruses
      were identified in the polyprotein and within individual proteins. Phylogenetic
      analysis indicated that the virus is most closely related to members of the BCMV
      subgroup. The results suggest that the virus should be classified as a novel
      species within the genus Potyvirus, which we tentatively name "Paris mosaic
      necrosis virus".

PMID- 29188365
TI  - A reaction-diffusion malaria model with seasonality and incubation period.
AB  - In this paper, we propose a time-periodic reaction-diffusion model which
      incorporates seasonality, spatial heterogeneity and the extrinsic incubation
      period (EIP) of the parasite. The basic reproduction number [Formula: see text]
      is derived, and it is shown that the disease-free periodic solution is globally
      attractive if [Formula: see text], while there is an endemic periodic solution
      and the disease is uniformly persistent if [Formula: see text]. Numerical
      simulations indicate that prolonging the EIP may be helpful in the disease
      control, while spatial heterogeneity of the disease transmission coefficient may
      increase the disease burden.

PMID- 29188366
TI  - Pre-operative neutrophil count and neutrophil-lymphocyte count ratio (NLCR) in
      predicting the histological grade of paediatric brain tumours: a preliminary
      study.
AB  - INTRODUCTION: The neutrophil-lymphocyte count ratio (NLCR) is an established
      prognostic marker for renal, lung and colorectal carcinomas and has been
      suggested to be predictive of histological grade and outcome in adult
      intracranial tumours. The purpose of this study was to determine whether a
      correlation of the pre-operative neutrophil count (NC) and NLCR with the final
      histological grade exists in paediatric intracranial tumours. METHODS: A
      retrospective analysis was undertaken at a single centre. Patients less than 18
      years old at the time of surgery who underwent tumour-related procedures from
      2006 to 2015 were included. Patients with recurrent tumours, previous bone marrow
      transplant and metastases were excluded. Pre-operative full blood counts (FBC),
      collected before the diagnosis of intracranial pathology and before
      administration of steroids, were matched with histological diagnosis for each
      patient. Post-operative FBC was also recorded, together with survival data where
      applicable. RESULTS: A total of 116 patients (74 male, 42 female; mean age, 8 +/-
      0.9 years) with a diagnosis of primary intracranial tumours had pre-operative FBC
      that could be matched to final histological grade. Pre-operative NC and NLCR were
      higher with increasing grade of tumour: grade 1 (NC 4.29 109/l, NLCR 2.26), grade
      2 (NC 4.59 109/l, NLCR 2.38), grade 3 (NC 5.67 109/l, NLCR 2.72) and grade 4 (NC
      6.59 109/l, NLCR 3.31). Patients with WHO grade 1 and 2 tumours pooled together
      had a lower NC (4.37 95% CI +/- 0.67 109/l) compared to WHO grade 3 and 4
      patients (6.41 95% CI +/- 0.99 109/l, p = 0.0013). The NLCR was lower in grade 1
      and 2 tumours (2.29 +/- 0.59) (compared to grade 3 and 4 tumours; 3.20 +/- 0.76)
      but this did not reach significance (p = 0.069). The subgroup of patients with
      pilocytic astrocytoma had a significantly lower NC when compared to patients with
      high-grade tumours (p = 0.005). Medulloblastoma and supratentorial PNET subgroups
      had significantly higher NC compared to the low-grade group (p = 0.033, p =
      0.002). Post-operative NC was significantly higher in the high-grade tumours (p =
      0.034), but no difference was observed for NLCR (p = 0.28). CONCLUSIONS: No
      evidence exists to support the correlation of pre-operative NC or NLCR to
      histological diagnosis in paediatric intracranial tumours. Our results indicate
      that a higher pre-operative NC/NLCR correlates with a higher histological grade
      of tumour. This suggests that immunological mechanisms may be involved in the
      pathogenesis of paediatric brain tumours, and a further prospective study is
      required to substantiate and expand these findings.

PMID- 29188367
TI  - Traumatic vertebral artery rupture causing intraspinal hematoma and progressive
      neurological symptoms.
AB  - Traumatic vertebral artery rupture is extremely rare. Herein, we report a case of
      traumatic vertebral artery rupture causing extensive intraspinal hematoma and
      progressive neurological symptoms.

PMID- 29188368
TI  - In vitro and in vivo thermal stress induces proliferation of Blastocystis sp.
AB  - Blastocystis sp. is known to be the most commonly found intestinal protozoan
      parasite in human fecal surveys and has been incriminated to cause diarrhea and
      abdominal bloating. Binary fission has been widely accepted as the plausible mode
      of reproduction for this parasite. The present study demonstrates that subjecting
      the parasites in vitro to higher temperature shows the proliferation of parasite
      numbers in cultures. Transmission electron microscopy was used to compare the
      morphology of Blastocystis sp. subtype 3 isolated from a dengue patient having
      high fever (in vivo thermal stress) and Blastocystis sp. 3 maintained at 41 
      degrees C (in vitro thermal stress) and 37  degrees C (control). Fluorescence
      stains like acridine orange (AO) and 4',6'-diamino-2-phenylindole (DAPI) were
      used to demonstrate the viability and nuclear content of the parasite for both
      the in vitro and in vivo thermal stress groups of parasites. Blastocystis sp. at
      37  degrees C was found to be mostly vacuolar whereas the in vitro thermal
      stressed isolates at 41  degrees C were granular with electron dense material
      seen to protect the granules within the central body. Parasites of the in vivo
      thermal stressed group showed similar ultrastructure as the in vitro ones. AO and
      DAPI staining provided evidence that these granules are viable which develop into
      progenies of Blastocystis sp. These granular forms were then observed to rupture
      and release progenies from the mother cells whilst the peripheral cytoplasmic
      walls were seen to degrade. Upon exposure to high temperature both in vitro and
      in vivo, Blastocystis sp. in cultures show higher number of granular forms seen
      to be protected by the electron dense material within the central body possibly
      acting as a protective mechanism. This is possibly to ensure the ability to
      survive for the granules to be developed as viable progenies for release into the
      host system.

PMID- 29188370
TI  - Predictors of cerclage failure in patients with singleton pregnancy undergoing
      prophylactic cervical cerclage.
AB  - PURPOSE: The role of cervical cerclage to prevent preterm birth (PTB) remains
      controversial. The aim of this study was to identify prognostic factors for
      cerclage failure among singleton pregnant women following prophylactic cerclage
      (PC). METHODS: A retrospective analysis of PC was performed in a single center.
      The main outcome measure was cerclage failure, defined by spontaneous early PTB
      prior to 32 weeks' gestation. Age, BMI, history of instrumentation of the uterus,
      history of second trimester miscarriage, previous conization, positive vaginal
      swab prior cerclage, gestational age at time of cerclage, CRP 1 week after
      cerclage and post-cerclage US changes of cervical length were tested as
      predictive factors. Descriptive statistical and binary logistic regression
      analyses were performed. RESULTS: 141 women underwent cerclage procedures between
      2007 and 2016. 39 patients had PC with McDonald suture, singleton pregnancy and
      complete clinical follow-up information, thus fulfilling the inclusion criteria.
      Multivariate analysis showed that history of instrumentation of the uterus was
      the only independent prognostic factor [OR = 0.14 (0.03, 0.72) p = 0.019] for
      cerclage failure. CONCLUSION: This is the first study showing that a history of
      previous uterine instrumentation is an independent predictor of cerclage failure.
      This finding has significant clinical implications for women of childbearing age,
      particularly when management of miscarriage/abortion is being considered. Women
      should be informed about the potential risks when counseled prior to surgical
      evacuation and medical management or cervical ripening should be considered.
      These results are also helpful in counseling patients undergoing cerclage, when a
      prior uterine instrumentation has been performed.

PMID- 29188371
TI  - Urinary iodine concentration and thyroid hormones: Korea National Health and
      Nutrition Examination Survey 2013-2015.
AB  - PURPOSE: An epidemiologic study that evaluated population's iodine nutrition
      status and its relationship with thyroid hormones is lacking in iodine-sufficient
      area. This nationwide study aimed to evaluate the iodine nutrition status in
      Korea and relationship between urine iodine concentration (UIC) and thyroid
      hormones. METHODS: A total of 8318 subjects of the Korea National Health and
      Nutrition Examination Survey VI (2013-2015) with UIC and thyroid hormone
      evaluation were included. Median UIC level and estimated 24-h iodine intake were
      calculated. The prevalence of iodine deficiency or excess was obtained using
      estimated average requirement or above the tolerable upper intake level cut-point
      method by estimated iodine intake. We analyzed UIC with regard to age, sex,
      social economic status, and geographic characteristics. RESULTS: The median UIC
      in general population and estimated iodine intake in adult population were 293.9
      MUg/L (above requirement according to World Health Organization classification)
      and 249.3MUg/day, respectively. The prevalence of iodine deficiency and excess
      was 14.0 and 13.4%. The median UIC was higher among SAC [511 (299.9-948.5)] and
      lower among seventies [251.2 (98.9-761.6)] compared to other age groups. The
      median UIC increased with household income level (p for trend < 0.001). The
      subjects living in rural and inland region had lowest UIC among the enrolled
      subjects. The subgroups with higher median UIC were associated with higher mean
      TSH levels. CONCLUSIONS: This first nationwide study in Korea demonstrated that
      the median of UIC and estimated iodine intake lie at nearly 300 ug/L and 250
      ug/day, respectively, which shows an overall excellent iodine nutrition.

PMID- 29188369
TI  - Immune modulation of Th1, Th2, and T-reg transcriptional factors differing from
      cytokine levels in Schistosoma japonicum infection.
AB  - In spite of long-term integrated control programs for Schistosoma japonicum
      infection in China, the infection is still persistent due to its zoonotic
      transmission and disease severity which further complicate its control. Th1, Th2,
      and T-reg cells are involved in S. japonicum immunity; however, their exact roles
      in immunopathology of this infection are still questionable. Therefore, the
      monitoring of these T cell subsets' immune responses during a primary infection
      of S. japonicum at both transcriptional (mRNA) and protein (cytokines) levels
      would be essential to point out. In experimentally infected white New Zealand
      rabbits, mRNA expression levels of TBX2, IRF8, GATA3, STAT6, FoxP3, and MAFF were
      evaluated using qPCR, whereas Th1 (IFN-gamma and TNF-alpha), Th2 (IL4 and IL13),
      and T-reg (IL10 and TGF-beta1) cytokines were measured by ELISA test. Those
      parameters were estimated at two phases: the first being 4 and 8 weeks post
      infection and the second phase at 12 weeks post-infection. The infected rabbits
      were categorized into group1 which was treated with praziquantel after the 8th
      week of infection and group 2 which was left untreated. In the first stage of
      infection, Th1 was superior to the other types at both mRNA (TBX2 and IRF8) and
      protein (IFN-gamma and TNF-alpha) levels, but at the late stage, Th2 cytokines
      (IL4 and IL13) were surprisingly dominated without comparable change in Th2
      transcriptional level in group 1. Concisely, the evaluation of T cell
      transcriptional factors provided clearer evidence about T cellular roles which
      would be a valuable supplement to control this disease in terms of protective and
      therapeutic vaccinations.

PMID- 29188372
TI  - Efficacy of ultrasound-guided core needle biopsy in cervical lymphadenopathy: A
      retrospective study of 6,695 cases.
AB  - OBJECTIVES: To determine the diagnostic yield of ultrasound-guided core needle
      biopsy (US-CNB) in cervical lymphadenopathy and identify the factors influencing
      the diagnostic accuracy of US-CNB. METHODS: We retrospectively reviewed the
      records of 6,603 patients with cervical lymphadenopathy who underwent 6695 US-CNB
      procedures between 2004 and 2017. RESULTS: Adequate specimens were obtained in
      92.19 % (6,172/6,695) of cases. Most lymph nodes (67.65 %) were malignant
      (metastatic carcinoma 4,131; lymphoma 398). The overall accuracy of US-CNB for
      differentiating benign from malignant lesions was 91.70 % (6,139/6,695). Among
      biopsies in which adequate material was obtained, the sensitivity, specificity
      and accuracy of US-CNB were 99.70 %, 100 % and 99.46 %, respectively. The success
      or failure of US-CNB for the diagnosis of lymphadenopathy was significantly
      correlated with node size, nature (malignant vs. benign), and location as well as
      penetration depth, but not with needle size (p = 0.665), number of core tissues
      obtained (p = 0.324), or history of malignancy (p = 0.060). There were no major
      procedure-related complications. CONCLUSIONS: US-CNB is a safe and effective
      method of diagnosing cervical lymphadenopathy, and our findings may help optimise
      the sampling procedure by maximising its diagnostic accuracy and preserving its
      minimally invasive nature. KEY POINTS: * US-CNB is useful for the diagnosis of
      cervical lymphadenopathy. * US-CNB is safe to perform on lymph nodes located near
      vital structures. * Larger, malignant, level IV lymph nodes yield sufficient
      tissue samples more easily.

PMID- 29188373
TI  - L5 pedicle subtraction osteotomy: indication, surgical technique and
      specificities.
AB  - PURPOSE: To evaluate the radiographic, functional outcomes, complications and
      surgical specificities of L5 pedicle subtraction osteotomy for fixed sagittal and
      coronal malalignment. METHODS: A retrospective cohort of consecutive patients
      with prospectively collected data. Ten patients who underwent PSO at L5 were
      eligible for a 2-year minimum follow-up (average, 4.0 years). Patients were
      evaluated by standardized upright radiographs. Preoperative and postoperative
      radiographies, surgical data and complications were collected. RESULTS: All
      surgeries were revision surgeries. The mean lumbar lordosis before surgery was -
      22.5 degrees  (range, 8 degrees  to - 33 degrees ) and improved to - 58.5 degrees
      (range, - 40 degrees  to - 79 degrees ). The sagittal vertical axis demonstrated
      a preoperative mean sagittal malalignment of 13.7 cm (range 3.5 to 20 cm), with
      correction to 4.6 cm postoperatively. Three patients required additional surgery
      at the latest follow-up for rod breakage. CONCLUSIONS: PSO of L5 can be a safe
      and effective technique to treat and correct fixed sagittal imbalance and provide
      biomechanical stability. The high complication rate mandates a careful assessment
      of the risk/benefit ratio of such a major surgery. Most patients are satisfied,
      particularly when sagittal balance is achieved.

PMID- 29188374
TI  - Characterization of a gene regulatory network underlying astringency loss in
      persimmon fruit.
AB  - MAIN CONCLUSION: Transcriptome analysis of a persimmon population segregating for
      an astringency trait in fruit suggested central roles for a limited number of
      transcriptional regulators in the loss of proanthocyanidin accumulation.
      Persimmon (Diospyros kaki; 2n = 6x = 90) accumulates a large amount of
      proanthocyanidins (PAs) in its fruit, resulting in an astringent taste. Persimmon
      cultivars are classified into four types based on the nature of astringency loss
      and the amount of PAs at maturity. Pollination constant and non-astringent (PCNA)
      type cultivars stop accumulating PAs in the early stages of fruit development and
      their fruit can be consumed when still firm without the need for artificial
      deastringency treatments. While the PCNA trait has been shown to be conferred by
      a recessive allele at a single locus (ASTRINGENCY; AST), the exact genetic
      determinant remains unidentified. Here, we conducted transcriptome analyses to
      elucidate the regulatory mechanism underlying this trait using developing fruits
      of an F1 population segregating for the PCNA trait. Comparisons of the
      transcriptomes of PCNA and non-PCNA individuals and hierarchical clustering
      revealed that genes related to the flavonoid pathway and to abiotic stress
      responses involving light stimulation were expressed coordinately with PA
      accumulation. Furthermore, coexpression network analyses suggested that three
      putative transcription factors were central to the PA regulatory network and that
      at least DkMYB4 and/or DkMYC1, which have been reported to form a protein complex
      with each other for PA regulation, may have a central role in the differential
      expression of PA biosynthetic pathway genes between PCNA and non-PCNA.

PMID- 29188375
TI  - Tunneled pleural catheter use for pleural palliation does not increase infection
      rate in patients with treatment-related immunosuppression.
AB  - PURPOSE: Concerns for infections resulting from antineoplastic therapy-associated
      immunosuppression may deter referral for symptom palliation with a tunneled
      pleural catheter (TPC) in patients with malignant/para-malignant pleural
      effusions (MPE/PMPE). While rates of TPC-related infections range from 1 to 21%,
      those in patients receiving antineoplastic therapy with correlation to immune
      status has not been established. We aimed to assess TPC-related infection rates
      in patients on antineoplastic therapy, determine relation to immune system
      competency, and assess impact on the patient. METHODS: Patients with a MPE/PMPE
      undergoing TPC management associated with antineoplastic therapy, from 2008 to
      2016, were reviewed and categorized into those with an immunocompromised versus
      immunocompetent immune status. RESULTS: Of the 150 patients, a TPC-related
      infection developed in 13 (9%): pleural space in 11 (7%) and superficial in 2
      (1%). Ninety-three percent (139/150) were identified to be immunocompromised
      during their antineoplastic therapy. No difference in TPC-related infections was
      seen in patients with an immunocompromised (9%, 12/139) versus immunocompetent
      status (9%, 1/11); p = 0.614. The presence of a catheter-related infection did
      not negatively impact overall survival over a median follow-up of 144 days
      (interquartile range 41-341); p = 0.740. CONCLUSIONS: These results suggest that
      antineoplastic therapy may not significantly increase the overall risk of TPC
      related infections, as the rate remains low and comparable to rates in patients
      not undergoing antineoplastic therapy. Regardless of immune status, the presence
      of a catheter-related infection did not negatively impact overall survival. These
      results should reassure clinicians that the need to initiate antineoplastic
      therapy should not delay definitive pleural palliation with a TPC.

PMID- 29188376
TI  - The role of direct oral anticoagulants in cancer-related venous thromboembolism:
      a perspective beyond the guidelines.
AB  - Cancer-related venous thromboembolism (Wickham et al., Intern Med J 42(6):698
      708, 2012) is an important source of morbidity and mortality in that population.
      The standard of care for the treatment of cancer-related venous thromboembolism
      (VTE) is a low molecular weight heparin (LMWH) for long periods of time. The
      favorable clinical trial results for efficacy and safety and availability of
      direct oral anticoagulants (DOAC) have remodeled the care and options for
      treatment of venous thromboembolism in the adult population. The data of cancer
      population-subgroup analysis of those studies have shown that DOAC are as
      effective and safe as conventional long-term oral anticoagulation with vitamin K
      antagonists (VKA). Additionally, non-controlled retrospective and prospective
      cohort data have been published describing efficacy and safety outcomes for the
      use of DOAC in cancer-related VTE. Altogether, the results from clinical studies
      have shown that direct oral anticoagulants may represent a treatment option for
      cancer-related VTE and an alternative to anticoagulation with VKA. Little is
      known about the patient-centered and system-based variables that determine the
      use of DOAC outside consensus guidelines, neither is known the impact of
      different anticoagulant modalities in adherence and quality of life in cancer
      patients. The objectives of this manuscript are to summarize the clinical trial
      based and cohort data of cancer patients treated with DOAC for VTE and to
      highlight the aspects that may influence adherent to therapy, effectiveness, and
      safety outcomes in the treatment of cancer-related VTE.

PMID- 29188377
TI  - Employer's management of employees affected by cancer.

PMID- 29188378
TI  - Receptor-driven, multimodal mapping of the human amygdala.
AB  - The human amygdala consists of subdivisions contributing to various functions.
      However, principles of structural organization at the cellular and molecular
      level are not well understood. Thus, we re-analyzed the cytoarchitecture of the
      amygdala and generated cytoarchitectonic probabilistic maps of ten subdivisions
      in stereotaxic space based on novel workflows and mapping tools. This
      parcellation was then used as a basis for analyzing the receptor expression for
      15 receptor types. Receptor fingerprints, i.e., the characteristic balance
      between densities of all receptor types, were generated in each subdivision to
      comprehensively visualize differences and similarities in receptor architecture
      between the subdivisions. Fingerprints of the central and medial nuclei and the
      anterior amygdaloid area were highly similar. Fingerprints of the lateral,
      basolateral and basomedial nuclei were also similar to each other, while those of
      the remaining nuclei were distinct in shape. Similarities were further
      investigated by a hierarchical cluster analysis: a two-cluster solution
      subdivided the phylogenetically older part (central, medial nuclei, anterior
      amygdaloid area) from the remaining parts of the amygdala. A more fine-grained
      three-cluster solution replicated our previous parcellation including a
      laterobasal, superficial and centromedial group. Furthermore, it helped to better
      characterize the paralaminar nucleus with a molecular organization in-between the
      laterobasal and the superficial group. The multimodal cyto- and receptor
      architectonic analysis of the human amygdala provides new insights into its
      microstructural organization, intersubject variability, localization in
      stereotaxic space and principles of receptor-based neurochemical differences.

PMID- 29188380
TI  - Correction to: Human baby hair amino acid natural abundance 15N-isotope values
      are not related to the 15N-isotope values of amino acids in mother's breast-milk
      protein.
AB  - In the article (Romek et al. 2013) we reported the values of delta15N (0/00) and
      delta13C (0/00) obtained by.

PMID- 29188379
TI  - Inguinal hernia repair by Bianchi incision in boys: a retrospective study.
AB  - OBJECTIVE: Open inguinal hernia repair by Bianchi incision is a potential
      alternative technique for the treatment of IH. This study aims to retrospectively
      analyze boys with IH, who underwent open IH repair by Bianchi incision. METHODS:
      A total of 3300 boys (1-144 months) with IH from April 2007 to September 2015
      were enrolled into this study. An open high scrotal incision (Bianchi incision)
      to ligate the processus proximal to the internal inguinal ring was performed in
      patients for IH repair. Then, all patients were followed up after 7 days, 1
      month, and 1 year. Operation time, hernia recurrence, hydrocele, testicular
      atrophy, cosmetic results, and the satisfaction of parents were evaluated.
      RESULTS: Among these 3300 boys, 1662 (50.36%) and 1349 (40.88%) boys with IH were
      operated on the right and left side, respectively, while 289 (8.76%) patients
      underwent bilateral surgery. The average operation time was 13.0 +/- 2.3 min for
      unilateral cases and 25.2 +/- 4.2 min for bilateral cases. Furthermore, among
      these 3300 boys, 309 boys (9.36%) were lost to follow-up, and the remaining 2991
      boys underwent a total of 3245 IH repairs. The complications included 20
      recurrences who were repaired with the same technique, one wound rupture, and one
      acquired undescended testis. No infection, obvious scrotal hematoma, testicular
      atrophy, and vas deferens injury were found during the follow-up. In most
      instances, the scars were invisible, obtaining an excellent cosmetic effect.
      CONCLUSION: Inguinal hernia repair by Bianchi incision is a safe, easy and
      effective technique with cosmetic benefits, which could be a reliable alternative
      for the treatment of pediatric inguinal hernia.

PMID- 29188381
TI  - The effect of Wolbachia on diapause, fecundity, and clock gene expression in
      Trichogramma brassicae (Hymenoptera: Trichogrammatidae).
AB  - The short day lengths of late summer in moderate regions are used to induce
      diapause in various insects. Many studies have shown the maternal effect of
      photoperiod on diapause induction of Trichogramma wasps, but there is no study to
      show the relationship between photoperiodic regimes and clock genes in these
      useful biological control agents. Here, we investigated the role of photoperiods
      on diapause, fecundity, and clock gene expression (clk, cyc, cry2, per, and
      timeout) in asexual and sexual Trichogramma brassicae as a model insect to find
      any differences between two strains. Asexual strain was infected by Wolbachia, an
      endosymbiont bacterium. The diapause percentage was significantly higher under
      short days (8 h in sexual and 12 h in the asexual T. brassicae), although the
      diapause percentage of the sexual strain was significantly higher than the
      asexual one in all the photoperiods. The ANOVA revealed no significant changes
      between different photoperiods in the clock gene expression in the sexual strain
      but significant photoperiodic changes in clk, cyc, and timeout in the asexual
      strain. Our results showed that the mRNA levels of clock genes of asexual T.
      brassicae were significantly lower than those of sexual strain. The fecundity was
      significantly higher in the asexual strain. These results suggest that Wolbachia
      infection makes disturbance on the clock gene expression which consequently
      reduces the percentage of diapause but increases the fecundity in asexual T.
      brassicae.

PMID- 29188382
TI  - Expression patterns of duplicated snail genes in the leech Helobdella.
AB  - snail gene family members are zinc-finger transcription factors with key roles in
      morphogenesis. Involvement of snail family genes in mesoderm formation has been
      observed in insects and mammals. The snail genes are also involved in cell
      motility, neural differentiation, cell fate, survival decision, and left-right
      identity. The functions of snail genes have been studied primarily among
      ecdysozoans and deuterostomes, with relatively little work carried out in
      lophotrochozoans. In this study, we isolated two snail homologs (Hau-snail1 and
      Hau-snail2) from the leech Helobdella austinensis. We characterized the temporal
      and spatial expression patterns of these two genes by semi-quantitative RT-PCR
      and in situ hybridization. The expression of Hau-snail1 and Hau-snail2 correlates
      with ventral nerve cord (VNC) development, segmental mesoderm, and with a ring of
      cells that comes to lie at the base of the leech proboscis, respectively, showing
      similarity to the divergent expression of duplicated snail genes in polychaetes.
      Our results do not support the function of lophotrochozoan snail genes in
      mesoderm specification.

PMID- 29188383
TI  - [Postoperative care and options for scar treatment in eyelid surgery].
AB  - Oculoplastic surgery places special demands on postoperative care because of the
      functional importance of the eyelids for the ocular surface. We present an
      overview of postoperative care after surgical eyelid interventions. All options,
      limits and the scientific evidence are discussed with a special focus on the
      treatment of postoperative edema, analgesia, infection prophylaxis and scar
      treatment.

PMID- 29188384
TI  - Long-term effects of complications and vascular comorbidity in idiopathic normal
      pressure hydrocephalus: a quality registry study.
AB  - BACKGROUND: There is little knowledge about the factors influencing the long-term
      outcome after surgery for idiopathic normal pressure hydrocephalus (iNPH).
      OBJECTIVE: To evaluate the effects of reoperation due to complications and of
      vascular comorbidity (hypertension, diabetes, stroke and heart disease) on the
      outcome in iNPH patients, 2-6 years after shunt surgery. METHODS: We included 979
      patients from the Swedish Hydrocephalus Quality Registry (SHQR), operated on for
      iNPH during 2004-2011. The patients were followed yearly by mailed
      questionnaires, including a self-assessed modified Rankin Scale (smRS) and a
      subjective comparison between their present and their preoperative health
      condition. The replies were grouped according to the length of follow-up after
      surgery. Data on clinical evaluations, vascular comorbidity, and reoperations
      were extracted from the SHQR. RESULTS: On the smRS, 40% (38-41) of the patients
      were improved 2-6 years after surgery and around 60% reported their general
      health condition to be better than preoperatively. Reoperation did not influence
      the outcome after 2-6 years. The presence of vascular comorbidity had no negative
      impact on the outcome after 2-6 years, assessed as improvement on the smRS or
      subjective improvement of the health condition, except after 6 years when
      patients with hypertension and a history of stroke showed a less favorable
      development on the smRS. CONCLUSION: This registry-based study shows no negative
      impact of complications and only minor effects of vascular comorbidity on the
      long-term outcome in iNPH.

PMID- 29188385
TI  - Association of diabetes therapy-related quality of life and physical activity
      levels in patients with type 2 diabetes receiving medication therapy: the
      Diabetes Distress and Care Registry at Tenri (DDCRT 17).
AB  - AIM: To examine the association between diabetes therapy-related quality of life
      (DTR-QOL) and physical activity levels, and identify factors associated with high
      diabetes therapy-related quality of life. METHODS: Cross-sectional data from 2970
      patients with type 2 diabetes in a Japanese diabetes registry were assessed for
      independent correlations between DTR-QOL (domains 1-4) and high physical activity
      levels. Data collected by the International Physical Activity Questionnaire were
      analyzed by logistic regression and adjusted for potential confounders. RESULTS:
      The mean patient age, BMI and HbA1c level were 65.8 years, 24.7 kg/m2 and 7.6%
      (58.7 mmol/mol), respectively. Univariate analysis showed that DTR-QOL domain 1,
      2 and 4 scores were significantly associated with physical activity levels (p =
      0.0046, p = 0.0004 and p < 0.001, respectively, but domain 3 score was not (p =
      0.5073). In a multivariable-adjusted logistic regression model, odds ratios (ORs)
      of DTR-QOL domains 1, 3 and 4 were independently associated with high physical
      activity (ORs for 2nd to 4th quartile and p for trend; [domain 1] 1.16, 1.56,
      1.22, p = 0.032; [domain 3] 1.45, 1.55, 1.38, p = 0.049; [domain 4] 1.09, 1.30,
      1.51, p = 0.001, respectively), but domain 2 was not (ORs for 2nd to 4th quartile
      and p for trend; 1.19, 1.26, 1.23, p = 0.096). CONCLUSION: High diabetes therapy
      related QOL scores were associated with high levels of physical activity in
      patients with type 2 diabetes. Because this is a cross-sectional study, further
      study is needed to evaluate the causal association between therapy-related QOL
      and physical activity.

PMID- 29188386
TI  - The shifting paradigm of a "cure" for type 1 diabetes: is technology replacing
      immune-based therapies?
AB  - Nearly 50 years after the autoimmune nature of type 1 diabetes was discovered, no
      therapy has been approved to alter the course of the disease at any stage.
      However, during that same period, technology has been delivering tools to help
      patients achieve better glycemic control and reduce the burden of the disease.
      With the imminent arrival of fully automated artificial pancreas systems that
      will continue to improve control and quality of life, it appears that we are on
      the verge of a major technological breakthrough that will significantly impact
      diabetes care. These devices have such a high degree of potential that they are,
      at times, mentioned as a virtual cure for the disease-a first for technology in
      this space. As such, these devices will undoubtedly alter the research landscape
      in a field that has predominantly been occupied by immunotherapies. This article
      reviews the history of type 1 diabetes and compares and contrasts the
      advancements that have come from the world of technology and immunology alike at
      this important crossroads in care that we are currently in.

PMID- 29188387
TI  - Efficacy and safety of twice-daily rabeprazole maintenance therapy for patients
      with reflux esophagitis refractory to standard once-daily proton pump inhibitor:
      the Japan-based EXTEND study.
AB  - BACKGROUND: Rabeprazole at 10 or 20 mg twice daily (b.i.d.) has been reported to
      be highly effective in the treatment of proton pump inhibitor (PPI)-resistant
      reflux esophagitis (RE) that is refractory to the standard once-daily PPI
      regimen. We evaluated the efficacy and safety of rabeprazole maintenance therapy
      at 10 mg once daily (q.d.) or b.i.d. for longer than 8 weeks. METHODS: Patients
      with RE refractory to standard PPI regimens for at least 8 weeks were enrolled.
      They were treated with rabeprazole at 10 or 20 mg b.i.d. for 8 weeks during the
      open-label treatment period. After endoscopic examination, those with confirmed
      healing entered the subsequent double-blind maintenance therapy. During this
      period, the subjects were randomized to receive rabeprazole 10 mg q.d. (control)
      or 10 mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at
      Week 52. RESULTS: In total, 517 subjects entered the treatment, and 359 subjects
      continued on maintenance therapy. The full analysis set for central assessment
      included 343 subjects. The no-recurrence rate at Week 52 was significantly higher
      in the b.i.d. group (73.9%; p < 0.001, chi2 test) than in the q.d. group (44.8%).
      In particular, the b.i.d. regimen was more effective in all subgroups with Los
      Angeles Classification Grade B to D at treatment entry. CONCLUSIONS: In the
      maintenance treatment of PPI-resistant RE, rabeprazole at 10 mg b.i.d. exerted a
      stronger recurrence-preventing effect than 10 mg q.d. over 52 weeks. No
      particular safety issues were noted during long-term administration.
      ClinicalTrials.gov number: NCT02135107.

PMID- 29188388
TI  - Learning the deformation mechanism of poly(vinylidine fluoride-co
      chlorotrifluoroethylene): an insight into strain-induced microstructure evolution
      via molecular dynamics.
AB  - Learning the micro-mechanisms of fluorinated polymers during mechanical response
      is more difficult than that of common polymers due to the unique intrinsic
      characteristics of the fluorine element. In this paper, we applied molecular
      dynamics simulations to study deformation mechanisms of poly(vinylidine fluoride
      co-chlorotrifluoroethylene) during uniaxial tension. We analyzed the variations
      of individual energy components and structural distribution curves versus strain
      in addition to the commonly used stress-strain curves and microstructure
      evolutions during stretching. The elastic limit is E = 0.02, E = 0.06 is the
      yield point, E = 0.24 is the termination of the softening, necking occurs at 0.24
      < E < 0.5, strain hardening occurs at 0.5 < E < 2.6, and E = 2.6 is the damage or
      brake point. The elastic behavior of the material does not rely on strain rate,
      the obvious effect of strain rate can be seen at the yield region and strain
      softening region, and the stress values are not influenced by strain rates at the
      softening and hardening stages. Overall, total potential energy is mainly
      correlated with non-bonded energy, and the proportion of DeltaEcoul overwhelms
      all the others. The energy components are ordered: DeltaEcoul > DeltaEvdwl > >
      DeltaEangle > DeltaEdihed > DeltaEbond. The chain conformation at yield point is
      almost unchanged compared with the pre-stretching conformation. The chain
      conformations at the end of strain softening changes more obviously than that at
      yield point. The molecular chains maintain random coil structure before strain
      hardening, and switch into a stretch chain conformation gradually during strain
      hardening. The maximum change in bond angle during the stretching process is F-C
      H, the largest change in bond length is the C-Cl bond, and the largest change in
      dihedral angle is H-C-C-H. The change of non-bonded interaction in the poly(VDF
      co-CTFE) system is much larger than the bonding interaction, and the main factor
      affecting bonding interaction is the change of angles. Graphical abstract
      Poly(vinylidine fluoride-co-chlorotrifluoroethylene) during tension?.

PMID- 29188389
TI  - Performance Evaluation of Time-Frequency Distributions for ECG Signal Analysis.
AB  - The non-stationary and multi-frequency nature of biomedical signal activities
      makes the use of time-frequency distributions (TFDs) for analysis inevitable.
      Time-frequency analysis provides simultaneous interpretations in both time and
      frequency domain enabling comprehensive explanation, presentation and
      interpretation of electrocardiogram (ECG) signals. The diversity of TFDs and
      specific properties for each type show the need to determine the best TFD for ECG
      analysis. In this study, a performance evaluation of five TFDs in term of ECG
      abnormality detection is presented. The detection criteria based on extracted
      features from most important ECG signal components (QRS) to detect normal and
      abnormal cases. This is achieved by estimating its energy concentration magnitude
      using the TFDs. The TFDs analyse ECG signals in one-minute interval instead of
      conventional time domain approach that analyses based on beat or frame containing
      several beats. The MIT-BIH normal sinus rhythm ECG database total records of 18
      long-term ECG sampled at 128 Hz have been analysed. The tested TFDs include Dual
      Tree Wavelet Transform, Spectrogram, Pseudo Wigner-Ville, Choi-Williams, and Born
      Jordan. Each record is divided into one-minute slots, which is not considered
      previously, and analysed. The sample periods (slots) are randomly selected ten
      minutes interval for each record. This result with 99.44% detection accuracy for
      15,735 ECG beats shows that Choi-Williams distribution is most reliable to be
      used for heart problem detection especially in automated systems that provide
      continuous monitoring for long time duration.

PMID- 29188390
TI  - A survival analysis using physique-adjusted tumor size of non-small cell lung
      cancer.
AB  - BACKGROUND: Differences in individual body sizes have not been well considered
      when analyzing the survival of patients with non-small cell lung cancer (NSCLC).
      We hypothesized that physique-adjusted tumor size is superior to actual tumor
      size in predicting the prognosis. METHODS: Eight hundred and forty-two patients
      who underwent R0 resection of NSCLC between 2005 and 2012 were retrospectively
      reviewed, and overall survival (OS) was evaluated. The physique-adjusted tumor
      size was defined as: x-adjusted tumor size = tumor size * mean value of
      x/individual value of x [x = height, weight, body surface area (BSA), or body
      mass index (BMI)]. Tumor size category was defined as <=2, 2-3, 3-5, 5-7, and >7
      cm. The separation index (SEP), which is the weighted mean of the absolute value
      of estimated regression coefficients over the subgroups with respect to a
      reference group, was used to measure the separation of subgroups. RESULTS: The
      mean values of height, weight, BSA, and BMI were 160.7 cm, 57.6 kg, 1.59 m2, and
      22.2 kg/m2, respectively. The 5-year survival rates ranged from 88-59% in the non
      adjusted tumor size model (SEP 1.937), from 90-57% in the height-adjusted model
      (SEP 2.236), from 91-52% in the weight-adjusted model (SEP 2.146), from 90-56% in
      the BSA-adjusted model (SEP 2.077), and from 91-51% in the BMI-adjusted model
      (SEP 2.169). CONCLUSIONS: The physique-adjusted tumor size can separate the
      survival better than the actual tumor size.

PMID- 29188391
TI  - Bisexual and Bidirectional: Assessing the Potential for HIV Bridging in
      Mozambique.
AB  - African men who have sex with men (MSM) frequently, and often concurrently, have
      female partners, raising concerns about HIV sexual bridging. We explored
      potential HIV transmission in Mozambique from and to female partners of MSM
      focusing on preferred anal sex role and circumcision status. Data collected in a
      respondent-driven sampling study of MSM in 2011 in Maputo and Beira. Men who had
      oral or anal sex with other men 12 months prior completed a questionnaire and
      consented for HIV testing. Statistical analysis explored demographic/risk
      characteristics and associations among circumcision status, anal sex with men,
      sexual positions during anal sex with men and vaginal or anal sex with women. We
      identified 326 MSM in Maputo and 237 in Beira with both male and female partners
      3 months before the study. Of these, 20.8% in Maputo and 36.0% in Beira had any
      receptive anal sex with men 12 months prior, including 895 unprotected sexual
      acts with males in Maputo and 692 in Beira. Uncircumcised and exclusively
      insertive males, 27.7% of the sample in Maputo and 33.6% in Beira, had the most
      unprotected sex with females: 1159 total acts in Maputo and 600 in Beira. Sexual
      bridging between MSM and women likely varies geographically and is probably bi
      directional, occurring within a generalized epidemic where HIV prevalence is
      higher among reproductive-age women than MSM. Prevention strategies emphasizing
      correct and consistent condom use for all partners and circumcision for bisexual
      men should be considered.

PMID- 29188392
TI  - Flow perfusion rate modulates cell deposition onto scaffold substrate during cell
      seeding.
AB  - The combination of perfusion bioreactors with porous scaffolds is beneficial for
      the transport of cells during cell seeding. Nonetheless, the fact that cells
      penetrate into the scaffold pores does not necessarily imply the interception of
      cells with scaffold substrate and cell attachment. An in vitro perfusion system
      was built to relate the selected flow rate with seeding efficiency. However, the
      in vitro model does not elucidate how the flow rate affects the transport and
      deposition of cells onto the scaffold. Thus, a computational model was developed
      mimicking in vitro conditions to identify the mechanisms that bring cells to the
      scaffold from suspension flow. Static and dynamic cell seeding configurations
      were investigated. In static seeding, cells sediment due to gravity until they
      encounter the first obstacle. In dynamic seeding, 12, 120 and 600 [Formula: see
      text] flow rates were explored under the presence or the absence of gravity.
      Gravity and secondary flow were found to be key factors for cell deposition. In
      vitro and in silico seeding efficiencies are in the same order of magnitude and
      follow the same trend with the effect of fluid flow; static seeding results in
      higher efficiency than dynamic perfusion although irregular spatial distribution
      of cells was found. In dynamic seeding, 120 [Formula: see text] provided the best
      seeding results. Nevertheless, the perfusion approach reports low efficiencies
      for the scaffold used in this study which leads to cell waste and low density of
      cells inside the scaffold. This study suggests gravity and secondary flow as the
      driving mechanisms for cell-scaffold deposition. In addition, the present in
      silico model can help to optimize hydrodynamic-based seeding strategies prior to
      experiments and enhance cell seeding efficiency.

PMID- 29188393
TI  - Recovery in Psychosis from a Service User Perspective: A Systematic Review and
      Thematic Synthesis of Current Qualitative Evidence.
AB  - There is a growing number of qualitative accounts regarding recovery from
      psychosis from a service user perspective. The aim of this study was to conduct a
      systematic review of these qualitative accounts. A thematic synthesis was
      utilised to synthesise and analyse seventeen studies included in the review.
      Studies were included if they used a qualitative methodology to explore service
      users' experiences of recovery from psychosis as a primary research question. All
      included studies were subjected to a quality assessment. The analysis outlined
      three subordinate themes: the recovery journey, facilitators of recovery (e.g.
      faith and spirituality, personal agency and hope), and barriers to recovery (e.g.
      stigma and discrimination, negative effects of mental health services and
      medication). Recovery is an idiosyncratic process but includes key components
      which are important to people who experience psychosis. These should be explored
      within clinical practice.

PMID- 29188394
TI  - Resonant reshaping of colloidal clusters on a current carrying wire.
AB  - Colloids in confined geometries promise a path towards tailored microscopic
      superstructures. Yet, a major roadblock is posed by kinetically trapped states
      that prevent the assemblies from reaching their anticipated shapes. We
      investigate magnetic colloids trapped on a cylindrical surface of a current
      carrying wire. If kinetic traps could be avoided the wire's surface would act as
      an ideal mold for colloidal rings and helical fibers. We devise here a way to
      dynamically shake down the clusters and avoid kinetic traps in their energy
      landscape. A low frequency magnetic modulation wave around the wire axis
      effectively eliminates defects from the clusters and stretches them into slender
      rings and helical filaments. A theoretical model is developed that qualitatively
      explains the observed resonant reshaping response of clusters.

PMID- 29188395
TI  - EMA Priority Medicines scheme (PRIME): will more paying-for-performance
      agreements be needed due to immature data?

PMID- 29188396
TI  - Cerebrovascular Hemodynamics During the Practice of Bhramari Pranayama,
      Kapalbhati and Bahir-Kumbhaka: An Exploratory Study.
AB  - Various pranayama techniques are known to produce different physiological
      effects. We evaluated the effect of three-different pranayama techniques on
      cerebrovascular hemodynamics. Eighteen healthy volunteers with the mean +/-
      standard deviation age of 23.78 +/- 2.96 years were performed three-different
      pranayama techniques: (1) Bhramari, (2) Kapalbhati and (3) Bahir-Kumbhaka in
      three-different orders. Continuous transcranial Doppler (TCD) monitoring was
      performed before, during and after the pranayama techniques. TCD parameters such
      as peak systolic velocity, end diastolic velocity (EDV), mean flow velocity (MFV)
      and pulsatility index (PI) of right middle cerebral artery were recorded.
      Practice of Kapalbhati showed significant reductions in EDV and MFV with
      significant increase in PI while, Bahir-Kumbhaka showed significant increase in
      EDV and MFV with significant reduction in PI. However, no such significant
      changes were observed in Bhramari pranayama. Various types of pranayama
      techniques produce different cerebrovascular hemodynamic changes in healthy
      volunteers.

PMID- 29188397
TI  - Comparison of machine learning and semi-quantification algorithms for (I123)FP
      CIT classification: the beginning of the end for semi-quantification?
AB  - BACKGROUND: Semi-quantification methods are well established in the clinic for
      assisted reporting of (I123) Ioflupane images. Arguably, these are limited
      diagnostic tools. Recent research has demonstrated the potential for improved
      classification performance offered by machine learning algorithms. A direct
      comparison between methods is required to establish whether a move towards
      widespread clinical adoption of machine learning algorithms is justified. This
      study compared three machine learning algorithms with that of a range of semi
      quantification methods, using the Parkinson's Progression Markers Initiative
      (PPMI) research database and a locally derived clinical database for validation.
      Machine learning algorithms were based on support vector machine classifiers with
      three different sets of features: Voxel intensities Principal components of image
      voxel intensities Striatal binding radios from the putamen and caudate. Semi
      quantification methods were based on striatal binding ratios (SBRs) from both
      putamina, with and without consideration of the caudates. Normal limits for the
      SBRs were defined through four different methods: Minimum of age-matched controls
      Mean minus 1/1.5/2 standard deviations from age-matched controls Linear
      regression of normal patient data against age (minus 1/1.5/2 standard errors)
      Selection of the optimum operating point on the receiver operator characteristic
      curve from normal and abnormal training data Each machine learning and semi
      quantification technique was evaluated with stratified, nested 10-fold cross
      validation, repeated 10 times. RESULTS: The mean accuracy of the semi
      quantitative methods for classification of local data into Parkinsonian and non
      Parkinsonian groups varied from 0.78 to 0.87, contrasting with 0.89 to 0.95 for
      classifying PPMI data into healthy controls and Parkinson's disease groups. The
      machine learning algorithms gave mean accuracies between 0.88 to 0.92 and 0.95 to
      0.97 for local and PPMI data respectively. CONCLUSIONS: Classification
      performance was lower for the local database than the research database for both
      semi-quantitative and machine learning algorithms. However, for both databases,
      the machine learning methods generated equal or higher mean accuracies (with
      lower variance) than any of the semi-quantification approaches. The gain in
      performance from using machine learning algorithms as compared to semi
      quantification was relatively small and may be insufficient, when considered in
      isolation, to offer significant advantages in the clinical context.

PMID- 29188398
TI  - Trastuzumab combined with doublet or single-agent chemotherapy as first-line
      therapy for HER2-positive metastatic breast cancer.
AB  - PURPOSE: To investigate the efficacy and safety of doublet versus single-agent
      chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal
      growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). METHODS:
      We searched for randomized clinical trials (RCTs) that evaluated the treatment
      effects of single-agent or doublet CT+H as first-line therapies for HER2-positive
      MBC. The main outcomes measured for this study included the overall response rate
      (ORR), progression-free survival (PFS), and overall survival (OS). A meta
      analysis and trial sequential analysis (TSA) were performed, and the study
      quality was evaluated using the GRADE framework. The PROSPERO registry number of
      our analysis is CRD42016043766. RESULTS: The results from four RCTs including
      1044 participants were pooled. Moderate-quality evidence indicated that compared
      with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard
      ratio [HR] 0.69, 95% confidence interval [CI] 0.63-0.75, P < 0.0001) and OS (HR =
      0.90, 95% CI 0.88-0.92, P < 0.0001). However, moderate-quality evidence revealed
      no significant difference between the two regimens regarding the ORR (relative
      risk [RR] = 1.07, 95% CI 0.98-1.17, P = 0.157), which was confirmed by TSA,
      indicating that the cumulative Z-curve entered the futility area. Moderate
      quality evidence indicated that treatment-related grade 3 or 4 toxicities of
      thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002),
      diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were
      observed more frequently with doublet CT+H than with single-agent CT+H.
      CONCLUSIONS: Compared with single-agent CT, the combination of doublet CT with
      trastuzumab as first-line therapy for HER2-positive MBC is associated with longer
      PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore,
      doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good
      performance status.

PMID- 29188400
TI  - Cellular injury to 1- to 3+-year-old stems of Camellia sinensis by Tuckerella
      japonica.
AB  - Tuckerella japonica Ehara (Acari: Tuckerellidae) feeds on predigested plant cells
      beneath exposed periderm tissue of 1- to 3+-year-old stems of Camellia sinensis
      (L.) O. Kuntze (Theaceae) where longitudinal bark splitting occurs. Control
      samples from these tissues were compared with areas fed upon by T. japonica
      adults and immatures to characterize types of cellular injury. Stylet diameters
      ranged from 1.6 to 2.3 um and were consistent with observed stylet punctures in
      the stems. Mite saliva was injected along tracts within the cortical tissue and
      resulted in cell wall disruption, collapsed cells and, in older tissue,
      hyperplasia. The range of potential stylet penetration into plant tissues was
      from 92 to 150 um. Tuckerella japonica injects saliva in the cortical tissues.
      The paired stylet lengths would allow for possible injection of saliva into the
      upper areas of phloem tissue but not in the cambium area of wood exposed by
      splitting of the outer epidermis.

PMID- 29188399
TI  - The alcoholic brain: neural bases of impaired reward-based decision-making in
      alcohol use disorders.
AB  - Neuroeconomics is providing insights into the neural bases of decision-making in
      normal and pathological conditions. In the neuropsychiatric domain, this
      discipline investigates how abnormal functioning of neural systems associated
      with reward processing and cognitive control promotes different disorders, and
      whether such evidence may inform treatments. This endeavor is crucial when
      studying different types of addiction, which share a core promoting mechanism in
      the imbalance between impulsive subcortical neural signals associated with
      immediate pleasurable outcomes and inhibitory signals mediated by a prefrontal
      reflective system. The resulting impairment in behavioral control represents a
      hallmark of alcohol use disorders (AUDs), a chronic relapsing disorder
      characterized by excessive alcohol consumption despite devastating consequences.
      This review aims to summarize available magnetic resonance imaging (MRI) evidence
      on reward-related decision-making alterations in AUDs, and to envision possible
      future research directions. We review functional MRI (fMRI) studies using tasks
      involving monetary rewards, as well as MRI studies relating decision-making
      parameters to neurostructural gray- or white-matter metrics. The available data
      suggest that excessive alcohol exposure affects neural signaling within brain
      networks underlying adaptive behavioral learning via the implementation of
      prediction errors. Namely, weaker ventromedial prefrontal cortex activity and
      altered connectivity between ventral striatum and dorsolateral prefrontal cortex
      likely underpin a shift from goal-directed to habitual actions which, in turn,
      might underpin compulsive alcohol consumption and relapsing episodes despite
      adverse consequences. Overall, these data highlight abnormal fronto-striatal
      connectivity as a candidate neurobiological marker of impaired choice in AUDs.
      Further studies are needed, however, to unveil its implications in the multiple
      facets of decision-making.

PMID- 29188401
TI  - Drought stress promotes the colonization success of a herbivorous mite that
      manipulates plant defenses.
AB  - Climate change is expected to bring longer periods of drought and this may affect
      the plant's ability to resist pests. We assessed if water deficit affects the
      tomato russet mite (TRM; Aculops lycopersici), a key tomato-pest. TRM thrives on
      tomato by suppressing the plant's jamonate defenses while these defenses
      typically are modulated by drought stress. We observed that the TRM population
      grows faster and causes more damage on drought-stressed plants. To explain this
      observation we measured several nutrients, phytohormones, defense-gene expression
      and the activity of defensive proteins in plants with or without drought stress
      or TRM. TRM increased the levels of total protein and several free amino acids.
      It also promoted the SA-response and upregulated the accumulation of jasmonates
      but down-regulated the downstream marker genes while promoting the activity of
      cysteine-but not serine-protease inhibitors, polyphenol oxidase and of peroxidase
      (POD). Drought stress, in turn, retained the down regulation of JA-marker genes
      and reduced the activity of serine protease inhibitors and POD, and altered the
      levels of some free-amino acids. When combined, drought stress antagonized the
      accumulation of POD and JA by TRM and synergized accumulation of free sugars and
      SA. Our data show that drought stress interacts with pest-induced primary and
      secondary metabolic changes and promotes pest performance.

PMID- 29188402
TI  - Development and characterisation of a large diameter decellularised vascular
      allograft.
AB  - The aims of this study were to develop a biological large diameter vascular graft
      by decellularisation of native human aorta to remove the immunogenic cells whilst
      retaining the essential biomechanical, and biochemical properties for the
      ultimate benefit of patients with infected synthetic grafts. Donor aortas (n = 6)
      were subjected to an adaptation of a propriety decellularisation process to
      remove the cells and acellularity assessed by histological analysis and
      extraction and quantification of total DNA. The biocompatibility of the acellular
      aortas was determined using standard contact cytotoxicity tests. Collagen and
      denatured collagen content of aortas was determined and immunohistochemistry was
      used to determine the presence of specific extracellular matrix proteins. Donor
      aortas (n = 6) were divided into two, with one half subject to decellularisation
      and the other half retained as native tissue. The native and decellularised aorta
      sections were then subject to uniaxial tensile testing to failure [axial and
      circumferential directions] and suture retention testing. The data was compared
      using a paired t-test. Histological evaluation showed an absence of cells in the
      treated aortas and retention of histoarchitecture including elastin content. The
      decellularised aortas had less than 15 ng mg-1 total DNA per dry weight (mean 94%
      reduction) and were biocompatible as determined by in vitro contact cytotoxicity
      tests. There were no gross changes in the histoarchitecture [elastin and collagen
      matrix] of the acellular aortas compared to native controls. The
      decellularisation process also reduced calcium deposits within the tissue. The
      uniaxial tensile and suture retention testing revealed no significant differences
      in the material properties (p > 0.05) of decellularised aorta. The
      decellularisation procedure resulted in minimal changes to the biological and
      biomechanical properties of the donor aortas. Acellular donor aorta has excellent
      potential for use as a large diameter vascular graft.

PMID- 29188403
TI  - Maternal Acceptance Moderates Fear Ratings and Avoidance Behavior in Children.
AB  - Avoidance is a hallmark feature of anxiety disorders, and avoidance-related
      impairment is often key to meeting diagnostic criteria. In children and
      adolescents with anxiety disorders, levels of avoidance vary considerably. Using
      a novel motion-tracking measure of avoidance behavior, we examined whether
      maternal acceptance, characterized by warm and accepting responses to child
      feelings and behaviors, moderates the association between fear of spiders and
      behavioral avoidance of spider stimuli in 103 clinically anxious children. As
      hypothesized, maternal acceptance significantly moderated children's avoidance
      behavior. Child's fear of spiders was significantly associated with behavioral
      avoidance when mothers were low in acceptance, as rated by either mothers or
      children. When mothers were high in acceptance, as rated by either mothers or
      children, child self-rated fear of spiders was not significantly associated with
      child avoidance. These are the first results to empirically demonstrate the
      moderating role of maternal acceptance in anxious children's avoidance behavior.

PMID- 29188404
TI  - Enhanced IgG1 production by overexpression of nuclear factor kappa B inhibitor
      zeta (NFKBIZ) in Chinese hamster ovary cells.
AB  - Several engineering strategies have been employed to improve the production of
      therapeutic recombinant proteins in Chinese hamster ovary (CHO) cell lines. We
      have focused on unfolded protein response-based engineering and reported that
      ATF4 overexpression increases protein production. In this study, transcriptome
      analysis of ATF4-overexpressed CHO cells was performed using high-coverage
      expression profiling, to search for another key factor contributing to
      recombinant protein production. We observed the upregulated expression of
      transcription factor, nuclear factor (NF)-kappa-B inhibitor zeta (NFKBIZ or
      Ikappabzeta), in ATF4-overexpressed cells. A total of 1917 bp of CHO NFKBIZ cDNA
      was cloned, and two stable cell lines overexpressing NFKBIZ were constructed. We
      investigated the effects of NFKBIZ on IgG1 production in CHO cells. Although the
      two stable cell lines, NFKBIZ-A and -B, had the opposite phenotypes in cell
      growth, the specific IgG1 production rate of both cell lines was enhanced by 1.2
      1.4-fold. In the NFKBIZ-A cell line, the synergistic effect between enhanced
      viable cell density and improved specific IgG1 production rate brought about a
      large increase in the final IgG1 titer. Luciferase-based NF-kappaB signaling
      assay results suggest that altered p50/p50 signaling seems to be due to the
      opposite phenotypes in cell growth. No difference was observed in the
      translational levels and intracellular assembly states of IgG1 between mock and
      two NFKBIZ cell lines, indicating that the secretion machinery of correctly
      folded IgG1 was enhanced in NFKBIZ-overexpressing cell lines.

PMID- 29188405
TI  - Promoting effects of adipose-derived stem cells on breast cancer cells are
      reversed by radiation therapy.
AB  - Partial breast irradiation of early breast cancer patients after lumpectomy and
      the use of endogenous adipose tissue (AT) for breast reconstruction are promising
      applications to reduce the side effects of breast cancer therapy. This study
      tries to investigate the possible risks associated with these therapeutic
      approaches. It also examines the influence of adipose derived stem cells (ADSCs)
      as part of the breast cancer microenvironment, and endogenous AT on breast cancer
      cells following radiation therapy. ADSCs, isolated from human reduction
      mammoplasties of healthy female donors, exhibited multilineage capacity and
      specific surface markers. The promoting effects of ADSCs on the growth and
      survival fraction of breast cancer cells were reversed by treatment with high (8
      Gy) or medium (2 Gy) radiation doses. In addition, a suppressing influence on
      breast cancer growth could be detected by co-culturing with irradiated ADSCs (8
      Gy). Furthermore the clonogenic survival of unirradiated tumor cells was reduced
      by medium of irradiated ADSCs. In conclusion, radiation therapy changed the
      interactions of ADSCs and breast cancer cells. On the basis of our work, the
      importance of further studies to exclude potential risks of ADSCs in regenerative
      applications and radiotherapy has been emphasized.

PMID- 29188406
TI  - O Gay New World: Ramifications of the Maternal Immune Hypothesis.

PMID- 29188407
TI  - Colonialist Pasts and Afrosurrealist Futures: Decolonizing Race and Doctorhood in
      Doctor Who.
AB  - Originally premiering in 1963, the BBC television series Doctor Who has long been
      criticized for essentializing colonial scenarios and failing to address issues of
      race and post-colonial realities. As a white male with the privilege to explore
      time and space, the titular Doctor stands in contrast to his human companion
      Martha Jones, a Black woman who represents the first and only main character in
      the show to be a medical professional of color. The relationship between the
      Doctor and Martha inherently demands an exploration of the meaning of doctorhood.
      In studying the ways in which these characters embody the idea of "doctor," we
      examine how race structures their approach to medicine, heroism, and colonialism.
      Whereas the Doctor personifies the figure of colonizer and post-colonial white
      savior, Martha emerges as a radical figure whose doctorhood potentially
      challenges and dismantles the colonial history of medicine. Through Afrofuturist
      and Afrosurrealist lenses, Martha represents a potentially subversive figure who
      offers a visionary medicine rooted in social justice.

PMID- 29188408
TI  - Phase IB Trial of the Anti-Cancer Stem Cell DLL4-Binding Agent Demcizumab with
      Pemetrexed and Carboplatin as First-Line Treatment of Metastatic Non-Squamous
      NSCLC.
AB  - BACKGROUND: Delta-like ligand 4-Notch (DLL4-Notch) signaling contributes to the
      maintenance of chemotherapy-resistant cancer stem cells and tumor vasculature.
      OBJECTIVE: This phase IB trial of demcizumab, an IgG2 humanized monoclonal
      antibody directed against DLL4, was undertaken to determine its maximum tolerated
      dose, safety, immunogenicity, preliminary efficacy, pharmacokinetics, and
      pharmacodynamics, combined with standard chemotherapy. PATIENTS AND METHODS:
      Forty-six treatment-naive patients with metastatic non-squamous non-small cell
      lung cancer (NSCLC) were enrolled in this open-label, dose-escalation study using
      a standard 6 + 6 design. Demcizumab (2.5, 5.0, and 7.5 mg/kg) was given once
      every 3 weeks with standard doses of pemetrexed and carboplatin using a
      continuous (six cycles followed by demcizumab maintenance) or a truncated
      demcizumab regimen (four cycles followed by pemetrexed maintenance). RESULTS:
      Initially, continuous demcizumab was given until progression but two patients
      developed grade 3 pulmonary hypertension and congestive heart failure after eight
      or more infusions. Thereafter, 23 patients were treated with a truncated regimen
      of demcizumab, which was not associated with any grade 3 or greater
      cardiopulmonary toxicity. Common adverse events were hypertension, raised brain
      natriuretic peptide, and those expected from carboplatin and pemetrexed alone.
      Twenty of 40 evaluable patients (50%) had objective tumor responses. In
      peripheral blood, demcizumab treatment modulated the expression of genes
      regulating Notch signaling and angiogenesis, and achieved concentrations
      exceeding those saturating DLL4 binding. CONCLUSIONS: This study has identified a
      truncated dosing regimen and recommended phase II dose of demcizumab (5 mg/kg q3
      weekly *4) for subsequent clinical evaluation in combination with standard
      carboplatin and pemetrexed chemotherapy. NCT01189968.

PMID- 29188409
TI  - Correction to: Dimensions of Peer Influences and Their Relationship to
      Adolescents' Aggression, Other Problem Behaviors and Prosocial Behavior.
AB  - Correction to: J Youth Adolescence (2017) 46:1351-1369. 10.1007/s10964-016-0601
      4.

PMID- 29188410
TI  - Developmental Pathways from Parental Socioeconomic Status to Adolescent Substance
      Use: Alternative and Complementary Reinforcement.
AB  - Although lower socioeconomic status has been linked to increased youth substance
      use, much less research has determined potential mechanisms explaining the
      association. The current longitudinal study tested whether alternative (i.e.,
      pleasure gained from activities without any concurrent use of substances) and
      complementary (i.e., pleasure gained from activities in tandem with substance
      use) reinforcement mediate the link between lower socioeconomic status and youth
      substance use. Further, we tested whether alternative and complementary
      reinforcement and youth substance use gradually unfold over time and then
      intersect with one another in a cascading manner. Potential sex differences are
      also examined. Data were drawn from a longitudinal survey of substance use and
      mental health among high school students in Los Angeles. Data collection involved
      four semiannual assessment waves beginning in fall 2013 (N = 3395; M baseline age
      = 14.1; 47% Hispanic, 16.2% Asian, 16.1% multiethnic, 15.7% White, and 5% Black;
      53.4% female). The results from a negative binomial path model suggested that
      lower parental socioeconomic status (i.e., lower parental education) was
      significantly related to an increased number of substances used by youth. The
      final path model revealed that the inverse association was statistically mediated
      by adolescents' diminished engagement in pleasurable substance-free activities
      (i.e., alternative reinforcers) and elevated engagement in pleasurable activities
      paired with substance use (i.e., complementary reinforcers). The direct effect of
      lower parental education on adolescent substance use was not statistically
      significant after accounting for the hypothesized mediating mechanisms. No sex
      differences were detected. Increasing access to and engagement in pleasant
      activities of high quality that do not need a reinforcement enhancer, such as
      substances, may be useful in interrupting the link between lower parental
      socioeconomic status and youth substance use.

PMID- 29188411
TI  - Callous-Unemotional Traits and Autonomic Functioning in Toddlerhood Interact to
      Predict Externalizing Behaviors in Preschool.
AB  - Callous-unemotional (CU) traits are one meaningful risk factor which helps to
      explain heterogeneity in the emergence of externalizing behavior problems. While
      the extant literature demonstrates links between early CU traits and later
      externalizing problems, there is a dearth of research examining for whom early CU
      traits confer risk. Data from a longitudinal study (n = 108) were used to examine
      the extent to which parasympathetic functioning moderated links between CU traits
      in toddlerhood (m age  = 24.99 months) and externalizing behavior problems at
      preschool-age (m age  = 51 months). Neither CU traits nor parasympathetic
      functioning at age 2 directly predicted later externalizing behaviors. However,
      results show that high levels of CU traits predict elevated externalizing
      behavior problems, but only for toddlers exhibiting either high baseline
      respiratory sinus arrhythmia (RSA) or little to no RSA suppression in response to
      a fear stimulus.

PMID- 29188412
TI  - Drug-related problems identified during geriatric medication review in the
      community pharmacy.
AB  - Background In line with the changing role of community pharmacists, we describe
      here a standardised procedure for detecting DRPs in elderly patients for use in
      community pharmacies. Objectives The primary aim was to describe the number and
      type of DRPs identified by community pharmacists in elderly patients. Secondary
      aims were to determine the number and type of associated pharmacist interventions
      (PIs) that were transmitted to the prescribers, and to identify risk factors
      associated with the occurrence of a PI. Setting Community pharmacies. Methods In
      this prospective, multicentre study, pharmacists received patients aged 65 and
      over. During a 30-min interview with patients who agreed to participate, patient
      characteristics were recorded such as age, weight, height, frailty (using the
      Short Emergency Geriatric Assessment grid), estimated renal function and
      compliance with treatment assessed by the Girerd scale. Main outcome measure DRPs
      characteristics. Results A total of 892 patients agreed to participate in 55
      pharmacies. Among them 334 DRPs were identified and were associated with 259 PIs.
      Eighty-nine PIs of 259 were sent to the prescribing physicians; 70 (78%) were
      implemented by the general practitioner. Factors associated with the occurrence
      of a DRP are compliance problems [odds ratio (OR) = 1.8, 95% confidence interval
      (CI) (1.26-2.58)], frailty [OR = 1.3, 95% CI (1.01-1.66)], number of prescribed
      drugs per day [OR = 1.46, 95% CI (1.02-2.07)] and GFR < 60 mL/min [OR = 1.49, 95%
      CI (1.01-2.2)]. Conclusion This is the first standardised pharmaceutical
      assessment dedicated to the elderly carried out by community pharmacists in
      France. If implemented, it could help to find drug-related problems, identify
      frail elderly patients and ultimately decrease their exposure to iatrogenic
      medication errors.

PMID- 29188413
TI  - Bioaccessibility of Phenolic Compounds and Antioxidant Capacity of Chia (Salvia
      hispanica L.) Seeds.
AB  - The aim of this work was to evaluate (i) the phenol and flavonoid recovery and
      bioaccessibility indexes and (ii) the antioxidant activity of both types of non
      defatted and defatted chia seeds during the in vitro gastrointestinal digestion.
      The ground samples were subjected to in vitro simulated gastrointestinal
      digestion, and the resultant fractions were extracted and subjected to
      spectrophotometric assays. The results pointed to increasing concentrations of
      polyphenolic compounds during digestion, although only a low-medium percentage of
      phenols and a low percentage of flavonoids were available for absorption in the
      intestinal tract. In addition, the high level of fats seemed to have a negative
      effect on the bioaccessibility of flavonoids. Further studies should be
      undertaken to better understand the stabilization of the bioactive compounds of
      chia and to improve their bioaccessibility. Meanwhile, the present study
      represents a solid base for studying the bioavailability of bioactive compounds
      of chia seeds.

PMID- 29188414
TI  - Velocity-pressure loops for continuous assessment of ventricular afterload:
      influence of pressure measurement site.
AB  - VPloop, the graphical representation of pressure versus velocity, and its
      characteristic angles, GALA and beta, can be used to monitor cardiac afterload
      during anesthesia. Ideally VPloop should be measured from pressure and velocity
      obtained at the same arterial location but standard of care usually provide
      either radial or femoral pressure waveforms. The purpose of this study was to
      look at the influence of arterial sites and the use of a transfer function (TF)
      on VPloop and its related angles. Invasive pressure signals were recorded in 25
      patients undergoing neuroradiology intervention under general anesthesia with
      transesophageal flow velocity monitoring. Pressures were recorded in the
      descending thoracic aorta, abdominal aorta, femoral and radial arteries. We
      compared GALA and beta from VPloops generated from each location and in high and
      low risk patients. GALA was similar in the central locations (55 degrees [49-63],
      52 degrees [47-61] and 54 degrees [45-62] from descending thoracic to femoral
      artery, median[interquartile], p = 0.10), while there was a difference in beta
      angle (16 degrees [4-27] to 8 degrees [3-15], p < 0.0001). GALA and beta obtained
      from radial waveforms were different (39 degrees [31-47] compared to 46 degrees
      [36-54] and 6 degrees [2-14] compared to 16 degrees [4-27] for GALA and beta
      angles respectively, p < 0.001) which was corrected by the use of a TF (45
      degrees [32-55] and 17 degrees [5-28], p = ns). GALA and beta are underestimated
      when measured with a radial catheter. Using pressure waveforms from femoral
      locations alters VPloops, GALA and beta in a smaller extend. The use of a TF on
      radial pressure allows to correctly plot VPloops and their characteristic angles
      for routine clinical use.

PMID- 29188415
TI  - Botanical origin of Mei-gui Hua in Chinese markets.
AB  - The petals or buds of Rosa species have been used as an important Chinese crude
      drug called "Mei-gui Hua" and also an ingredient for herbal tea in China. The 15
      flavonol glycosides in 34 commercially available "Mei-gui Hua" were
      quantitatively determined by UPLC, and the data were compared with those of known
      Rosa sp. belong to Cinnamomeae, Gallicanae, Caninae and Synstylae by principal
      component analysis for the estimation of original plants of these "Mei-gui Hua".
      Seven samples were classified into two groups (Types A and B) composed of species
      in Gallicae and Synstilae and 11 samples into a group (Type D) composed of
      species in Cinnamomeae. Six samples were plotted among Types B, C and D. However,
      nine samples were shown to form a new group (Type F), and the original plants of
      these samples were assumed to be more complex hybrids of Rosa species including
      other sections than Cinnamomeae, Gallicanae, Caninae and Synstylae. This method
      must be useful and convenient to estimate the origin of crude drug "Mei-gui Hua"
      commercially available in markets. The results of this study also demonstrated
      that "Mei-gui Hua" commercially available in Chinese market must be prepared from
      hybrids of various species of Rosa, and it is not reasonable to assign only R.
      rugosa as scientific name of the origin plants.

PMID- 29188416
TI  - Production of an emericellin and its analogues as fungal biological responses for
      Shimbu-to extract.
AB  - This research examined the production of fungal metabolites as a biological
      response to Kampo medicines. Shimbu-to (SMB) is a Kampo medicine composed of five
      herbal components: peony root (Shakuyaku), ginger (Shokyo), processed aconite
      root (Bushi), Poria sclerotium (Bukuryo), and Atractylodes lancea rhizomes
      (Sojutsu). High-performance liquid chromatography (HPLC) analysis of the fungus
      Aspergillus nidulans CBS 112.46 incubated in potato dextrose broth supplemented
      with SMB extract revealed emericellin (2) as the major peak and new xanthone
      analogues 24-hydroxyshamixanthone (1), shamixanthone (3), epishamixanthone (4),
      pre-shamixanthone (5), and variecoxanthone A (6) as minor peaks. The structure of
      1 was determined by detailed analysis of 1D-NMR, 2D-NMR, and MS data. The results
      suggest that SMB extract regulates the biosynthesis of emericellin and its
      analogues in A. nidulans. Further investigations revealed that glucose induces
      the biosynthesis of emericellin and its analogues in A. nidulans in a
      concentration-dependent manner.

PMID- 29188417
TI  - Simultaneous determination of fast and slow dynamics in molecules using extreme
      CPMG relaxation dispersion experiments.
AB  - Molecular dynamics play a significant role in how molecules perform their
      function. A critical method that provides information on dynamics, at the atomic
      level, is NMR-based relaxation dispersion (RD) experiments. RD experiments have
      been utilized for understanding multiple biological processes occurring at micro
      to-millisecond time, such as enzyme catalysis, molecular recognition, ligand
      binding and protein folding. Here, we applied the recently developed high-power
      RD concept to the Carr-Purcell-Meiboom-Gill sequence (extreme CPMG; E-CPMG) for
      the simultaneous detection of fast and slow dynamics. Using a fast folding
      protein, gpW, we have shown that previously inaccessible kinetics can be accessed
      with the improved precision and efficiency of the measurement by using this
      experiment.

PMID- 29188419
TI  - Comparison of the outcome between unilateral and bilateral open wedge high tibial
      osteotomy in the bilateral varus knees.
AB  - INTRODUCTION: Bilateral open wedge high tibial osteotomy (OWHTO) can be performed
      in a staged manner to enable the healing and rehabilitation of each limb
      separately after surgery. However, the effects of staged bilateral OWHTO on the
      pattern of recovery and changes over time for each limb have not been
      established. Additionally, there is a lack of information regarding the optimal
      timing for staged surgery. METHODS: Twenty-two patients (44 knees) in the
      bilateral OWHTO group and 42 patients (42 knees) in the unilateral OWHTO group
      were analyzed. Clinical and radiological results were evaluated and compared
      between the two groups. For the alignment change assessment, the hip-knee-ankle
      (HKA) angle and weight-bearing line (WBL) ratio were measured preoperatively and
      at postoperative 6 weeks, 3 months, 6 months, and 1 year. RESULTS: The correction
      loss of HKA angle in the bilateral OWHTO group was significantly larger than that
      in the unilateral OWHTO group (0.5 degrees  +/- 1.4 degrees  vs 1.3 degrees  +/-
      2.0 degrees , p = 0.049). The correction loss of WBL ratio was significantly
      greater in the patients with staged bilateral OWHTO within a 3-month interval
      compared to those with staged bilateral OWHTO in an interval longer than 3 months
      (WBL ratio; 7.5% vs 2.1%, p = 0.01). There was no significant difference in the
      clinical scores and range of motion at the last follow-up. CONCLUSION: The
      smaller loss of correction in the unilateral OWHTO group occurred compared to the
      bilateral OWHTO group. Additionally, surgeons should keep in mind that the amount
      of correction loss may be greater if staged bilateral OWHTO is performed at
      intervals of 3 months or less.

PMID- 29188418
TI  - Imaging of Nanoparticle Distribution to Assess Treatments That Alter Delivery.
AB  - Molecular imaging is a vital tool to non-invasively measure nanoparticle delivery
      to solid tumors. Despite the myriad of nanoparticles studied for cancer,
      successful applications of nanoparticles in humans is limited by inconsistent and
      ineffective delivery. Successful nanoparticle delivery in preclinical models is
      often attributed to enhanced permeability and retention (EPR)-a set of conditions
      that is heterogeneous and transient in patients. Thus, researchers are evaluating
      therapeutic strategies to modify nanoparticle delivery, particularly treatments
      which have demonstrated effects on EPR conditions. Imaging nanoparticle
      distribution provides a means to measure the effects of therapeutic intervention
      on nanoparticle delivery to solid tumors. This review focuses on the utility of
      imaging to measure treatment-induced changes in nanoparticle delivery to tumors
      and provides preclinical examples studying a broad range of therapeutic
      interventions.

PMID- 29188420
TI  - A lateral retinacular release during total knee arthroplasty changes femorotibial
      kinematics: an in vitro study.
AB  - INTRODUCTION: Lateral retinacular release (LRR) is a common procedure during
      total knee arthroplasty (TKA), especially if patellar maltracking is observed
      intraoperatively. The impact of LRR on patellofemoral kinematics is well
      examined, but the influence on femorotibial kinematics requires more elucidation.
      Therefore, the aim of this study was to evaluate the effects of LRR on
      femorotibial kinematics in vitro. MATERIALS AND METHODS: A fixed bearing TKA was
      implanted in six human knee specimens. Femorotibial kinematics were measured
      dynamically through the use of a custom-constructed knee rig which flexes the
      knee from 20 degrees  to 120 degrees  under weight bearing conditions.
      Measurements were performed before and after LRR. LRR was performed completely
      including transection of synovium, retinaculum and tractus fibers. For the
      registration of tibiofemoral kinematics a 3-dimensional-ultrasound-based motion
      analysis system was used. RESULTS: LRR revealed a significant reduction of
      femoral rollback at the lateral compartment (9.4 +/- 5.0 vs 7.8 +/- 9.4 mm; p <
      0.01), whereas the present decrease of femoral rollback at the medial compartment
      was not significant (3.4 +/- 4.7 vs 2.3 +/- 5.9 mm; p = 0.34). Accordingly, LRR
      significantly reduced internal rotation of the tibia (0.8 degrees ; p < 0.01).
      CONCLUSION: The results suggest that LRR significantly decreases lateral femoral
      rollback as well as internal rotation of the tibia, probably by changing the
      tension of the iliotibial band. When performing a LRR in clinical routine,
      surgeons should be aware of altering not only patellofemoral kinematics but also
      the femorotibial kinematics.

PMID- 29188421
TI  - Arthroscopic partial meniscectomy in young patients with symptomatic discoid
      lateral meniscus: an average 10-year follow-up study.
AB  - INTRODUCTION: The aim of this study is to evaluate mid-to-long-term clinical and
      radiological outcomes after an arthroscopic partial meniscectomy for symptomatic
      discoid lateral meniscus (DLM) in young patients and to determine whether
      degeneration of the residual meniscus and articular cartilage progresses during
      the follow-up period using magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: We retrospectively reviewed patients aged <= 40 years at surgery who
      underwent arthroscopic partial meniscectomy for symptomatic DLM and were followed
      up for >= 5 years. Lysholm knee scores and reoperation rates were assessed as
      clinical outcomes. Factors that affect clinical outcomes were evaluated. Tapper
      Hoover classification and femorotibial angle were used for radiological
      assessment. The degree of degeneration of articular cartilages and residual
      meniscus was evaluated using preoperative and follow-up MRIs. RESULTS: A total of
      73 knees (66 patients) were enrolled. The mean follow-up period was 10.0 years.
      The mean follow-up Lysholm knee score was 84.2 +/- 14.5, and the reoperation rate
      was 32.9%. Follow-up Lysholm knee scores were related to duration of symptoms
      prior to surgery (beta = - 0.129, P = 0.003) and femorotibial angle at the last
      follow-up (beta = 1.362, P = 0.045). On simple radiographs, progression of
      arthritis of the lateral compartment was observed in 68.5% (49 knees). In MRI
      analyses, degeneration of the residual meniscus progressed in 52.9% (34 knees) (P
      < 0.001), and significant changes in modified Yulish scores were observed in both
      lateral femoral and tibial condyles (P < 0.001, both condyles). CONCLUSIONS:
      After an arthroscopic partial meniscectomy for symptomatic DLM, unfavorable
      clinical outcomes were shown in > 30% of the patients during a mean follow-up of
      10.0 years. Clinical outcomes based on the patient-reported outcome measures were
      related to durations of symptoms prior to surgery and alignment at the last
      follow-up. In radiological and MRI assessments, progression of degeneration of
      articular cartilages in the lateral compartments of the knees and residual
      menisci was observed.

PMID- 29188422
TI  - Climbing plants: attachment adaptations and bioinspired innovations.
AB  - Climbing plants have unique adaptations to enable them to compete for sunlight,
      for which they invest minimal resources for vertical growth. Indeed, their stems
      bear relatively little weight, as they traverse their host substrates skyward.
      Climbers possess high tensile strength and flexibility, which allows them to
      utilize natural and manmade structures for support and growth. The climbing
      strategies of plants have intrigued scientists for centuries, yet our
      understanding about biochemical adaptations and their molecular undergirding is
      still in the early stages of research. Nonetheless, recent discoveries are
      promising, not only from a basic knowledge perspective, but also for bioinspired
      product development. Several adaptations, including nanoparticle and adhesive
      production will be reviewed, as well as practical translation of these
      adaptations to commercial applications. We will review the botanical literature
      on the modes of adaptation to climb, as well as specialized organs-and cellular
      innovations. Finally, recent molecular and biochemical data will be reviewed to
      assess the future needs and new directions for potential practical products that
      may be bioinspired by climbing plants.

PMID- 29188423
TI  - Augmented marker tracking for peri-acetabular osteotomy surgery.
AB  - OBJECTIVE: To develop a hybrid augmented marker-based navigation system for
      acetabular reorientation during peri-acetabular osteotomy (PAO). METHODS: The
      system consists of a tracking unit attached to the patient's pelvis, augmented
      marker attached to the acetabular fragment and a host computer to do all the
      computations and visualization. The augmented marker is comprised of an external
      planar Aruco marker facing toward the tracking unit and an internal inertial
      measurement unit (IMU) to measure its orientation. The orientation output from
      the IMU is sent to the host computer. The tracking unit streams a live video of
      the augmented marker to the host computer, where the planar marker is detected
      and its pose is estimated. A Kalman filter-based sensor fusion combines the
      output from marker tracking and the IMU. We validated the proposed system using a
      plastic bone study and a cadaver study. Every time, we compared the inclination
      and anteversion values measured by the proposed system to those from a previously
      developed optical tracking-based navigation system. RESULTS: Mean absolute
      differences for inclination and anteversion were 1.34 ([Formula: see text]) and
      1.21 ([Formula: see text])[Formula: see text], respectively, for the cadaver
      study. Mean absolute differences were 1.63 ([Formula: see text]) and 1.55
      ([Formula: see text])[Formula: see text] for inclination and anteversion for the
      plastic bone study. In both validation studies, very strong correlations were
      observed. CONCLUSION: We successfully demonstrated the feasibility of our system
      to measure the acetabular orientation during PAO.

PMID- 29188424
TI  - Increase in Mitochondrial Biogenesis in Neuronal Cells by RNS60, a Physically
      Modified Saline, via Phosphatidylinositol 3-Kinase-Mediated Upregulation of
      PGC1alpha.
AB  - This study highlights a novel approach to upregulate mitochondrial biogenesis in
      neuronal cells. RNS60 is a 0.9% saline solution containing oxygenated nanobubbles
      that is generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP)
      flow under elevated oxygen pressure. RNS60, but not NS (normal saline), PNS60
      (saline containing a comparable level of oxygen without the TCP modification), or
      RNS10.3 (TCP-modified normal saline without excess oxygen), increased the
      expression of Nrf1, Tfam, Mcu, and Tom20 (genes associated with mitochondrial
      biogenesis) and upregulated mitochondrial biogenesis in MN9D dopaminergic
      neuronal cells. Similarly RNS60 also increased mitochondrial biogenesis in
      primary dopaminergic neurons and in the nigra of MPTP-intoxicated mice. However,
      RNS60 had no effect on lysosomal biogenesis. Interestingly, we found that RNS60
      upregulated PGC1alpha and siRNA knockdown of PGC1alpha abrogated the ability of
      RNS60 to increase mitochondrial biogenesis. Furthermore, we delineated that RNS60
      increased the transcription of Pgc1a via type IA phosphatidylinositol (PI) 3
      kinase-mediated activation of cAMP-response element-binding protein (CREB).
      Accordingly, knockdown of the PI3K - CREB pathway suppressed RNS60-mediated
      mitochondrial biogenesis. These results describe a novel property of RNS60 of
      enhancing mitochondrial biogenesis via PI 3-kinase-CREB-mediated up-regulation of
      PGC1alpha, which may be of therapeutic benefit in different neurodegenerative
      disorders.

PMID- 29188425
TI  - Increased benefit of betrixaban among patients with a history of venous
      thromboembolism: a post-hoc analysis of the APEX trial.
AB  - : Hospitalized acute medically ill patients with a history of venous
      thromboembolism (VTE) are at increased risk for recurrent VTE. We characterized
      the efficacy and safety of betrixaban for prevention of recurrent VTE in these
      high risk patients. The APEX trial randomized 7513 acutely ill hospitalized
      medical patients at risk for developing VTE to receive either betrixaban for 35
      42 days or enoxaparin for 10 +/- 4 days to prevent VTE. This exploratory post-hoc
      analysis assessed the efficacy and safety of betrixaban versus enoxaparin among
      subjects with and without prior VTE. Time-to-multiple symptomatic VTE events was
      also calculated. Approximately 8% of subjects in both arms had prior VTE, which
      was associated with a fourfold increase in adjusted risk of VTE [MV OR 4.03, 95%
      CI 3.06-5.30, p < 0.001]. Betrixaban reduced VTE compared with enoxaparin among
      subjects with prior VTE [32 (10.4%) vs. 55 (18.9%), RR 0.57, 95% CI 0.38-0.86, p
      = 0.006, ARR 8.5%, NNT 12] and without prior VTE [133 (3.9%) vs. 168 (4.9%), RR
      0.79, 95% CI 0.64-0.99, p = 0.042, ARR 1.0%, NNT 100] (interaction p > 0.05).
      Additionally, four subjects in the enoxaparin arm and one subject in the
      betrixaban arm experienced a recurrent VTE. Compared with enoxaparin, betrixaban
      use was associated with reduction of recurrent VTE events through the active
      treatment period [36 vs. 57, HR 0.63, 95% CI 0.41-0.97, p = 0.045] and through
      the end of study [38 vs. 71, HR 0.54, 95% CI 0.36-0.81, p = 0.004]. Prior VTE is
      associated with a fourfold increase in the risk of VTE among hospitalized
      medically ill patients. Only 12 such patients would need to be treated with
      betrixaban versus enoxaparin to prevent an additional VTE endpoint. Betrixaban
      reduced not only the first but also all recurrent VTE events in a time-to-any
      event analysis. TRIAL REGISTRATION: http://www.clinicaltrials.gov , Unique
      identifier: NCT01583218.

PMID- 29188426
TI  - Investigating the contribution of task and response repetitions to the sequential
      modulations of attentional cueing effects.
AB  - We tested the nature of validity sequence effects. During visual search for
      targets, target-preceding peripheral cues at target position (valid condition)
      facilitate search relative to cues away from the target (invalid condition). This
      validity effect (i.e., advantage in valid compared to invalid conditions) is
      observed for cues that are not predictive of the target, and it reflects the
      cue's capture of attention. Importantly, the validity effect is stronger
      following valid than invalid trials. The underlying causes of this validity
      sequence effect are unknown. We, therefore, tested if the validity sequence
      effect reflected trial-to-trial priming or event-file coding. According to these
      explanations, full trial-to-trial repetitions and full changes of all stimulus
      features or of all stimulus and response features, respectively, would account
      for the validity sequence effect. However, the validity sequence effect could
      also reflect the participants' retention of a recently helpful cue (i.e., after a
      valid trial) and/or their suppression of a recently harmful cue (i.e., after an
      invalid trial). Here, to contrastively test these theories, from trial to trial,
      the tasks are repeated or switched. The results demonstrated that, under certain
      conditions, the validity sequence effect can survive task-switching (Experiments
      1 and 2), which supports the retention/suppression account. When the tasks were
      strongly distinguished, however, the validity sequence effect did not survive
      task-switching (Experiment 3), which supports the event-coding account. Together,
      the results suggest that task structure can determine the impact of cue
      processing on subsequent trials, and the extent to which it reflects event-file
      coding.

PMID- 29188428
TI  - Surgical treatment for endocardial radiofrequency ablation-resistant sustained
      monomorphic ventricular tachycardia with mural thrombus including dense
      calcification in the left ventricle.
AB  - Catheter ablation provides effective results for sustained monomorphic
      ventricular tachycardia (VT), but the presence of mural thrombus including dense
      calcification occasionally causes unfavorable outcomes. The case of a 67-year-old
      man in whom sustained monomorphic VT, which was resistant to endocardial
      radiofrequency ablation, in the presence of mural thrombus including dense
      calcification after coronary artery bypass grafting was successfully treated by
      left ventricular reconstruction with cryoablation is reported.

PMID- 29188429
TI  - Spike in glucose levels after reperfusion during aortic surgery: assessment by
      continuous blood glucose monitoring using artificial endocrine pancreas.
AB  - OBJECTIVES: Although strict blood glucose control during cardiovascular surgery
      is essential to avoid postoperative complications, the various changes in glucose
      levels that occur during surgery have not been investigated in detail. In this
      study, we continuously monitored blood glucose changes during aortic surgery
      using the STG-55R artificial endocrine pancreas (Nikkiso Inc., Tokyo). METHODS:
      Between December 2015 and 2016, we performed continuous blood glucose monitoring
      in 22 patients (14 men and 8 women, 72 +/- 11 years old), who required
      hypothermic circulatory arrest during an ascending/aortic arch surgery, at the
      Jichi Medical University Hospital. Ascending aorta replacements were performed in
      two patients and partial/total arch replacement, in 20. All the patients required
      selective cerebral perfusion and hypothermic circulatory arrest (bladder
      temperature at 25-26  degrees C) during distal anastomosis. Closed-loop
      continuous blood glucose monitoring was performed during cardiopulmonary bypass
      using the STG-55R artificial endocrine pancreas (Nikkiso Co., LTD, Tokyo).
      RESULTS: Blood glucose concentrations did not increase significantly from the
      time of the commencement of cardiopulmonary bypass to lower body ischemia.
      However, they dramatically increased immediately after reperfusion following
      lower body ischemia, and this hyperglycemia was sustained until the end of
      cardiopulmonary bypass. CONCLUSION: The current study clarified the peak glucose
      concentration during aortic surgery. These data may contribute to the management
      of blood glucose levels during aortic surgery.

PMID- 29188430
TI  - Undiagnosed mitroflow bioprosthesis deformation causing early structural valve
      deterioration.
AB  - Bioprosthesis are commonly used in the elderly population. Structural valve
      deterioration affects the long-term durability. We report an early deterioration
      of a Mitroflow valve caused by ring deformation and prosthetic leaflet rupture.
      The 69-years-old patient underwent successful redo surgery with excision of the
      bioprosthesis and placement of a mechanical valve.

PMID- 29188427
TI  - Recent progress on chikungunya virus research.
AB  - Chikungunya virus (CHIKV) is an arbovirus transmitted by Aedes mosquitos in
      tropical and subtropical regions across the world. After decades of sporadic
      outbreaks, it re-emerged in Africa, Asia, India Ocean and America suddenly,
      causing major regional epidemics recently and becoming a notable global health
      problem. Infection by CHIKV results in a spectrum of clinical diseases including
      an acute self-limiting febrile illness in most individuals, a chronic phase of
      recurrent join pain in a proportion of patients, and long-term arthralgia for
      months to years for the unfortunate few. No specific anti-viral drugs or licensed
      vaccines for CHIKV are available so far. A better understanding of virus-host
      interactions is essential for the development of therapeutics and vaccines. To
      this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical
      presentation, molecular virology, diagnostic approaches, host immune response,
      vaccine development, and available animal models. Such a comprehensive overview,
      we believe, will shed lights on the promises and challenges in CHIKV vaccine
      development.

PMID- 29188431
TI  - Cardiac ATTR amyloid nuclear imaging-not all bone scintigraphy radionuclide
      tracers are created equal.

PMID- 29188432
TI  - 18F-FDG PET/CT now endorsed by guidelines across all types of CIED infection:
      Evidence limited but growing.

PMID- 29188433
TI  - Deciding wisely: A case for an effective use of myocardial perfusion imaging.
AB  - There is a vast body of literature supporting the use of stress myocardial
      perfusion imaging (MPI) in patients with known or suspected coronary artery
      disease. When applied in the appropriate clinical setting, MPI can aid, not only
      in diagnosis and risk stratification, but also in decision-making. In a case of a
      58-year-old man with suspected coronary artery disease, we highlight how the
      appropriate use of stress MPI can leverage the diagnostic and prognostic utility
      of MPI in an effective, evidence-based decision-making aimed to achieve the best
      patient outcome.

PMID- 29188434
TI  - Photothrombotic Stroke as a Model of Ischemic Stroke.
AB  - The search of effective anti-stroke neuroprotectors requires various stroke
      models adequate for different aspects of the ischemic processes. The
      photothrombotic stroke model is particularly suitable for the study of cellular
      and molecular mechanisms underlying neurodegeneration, neuroprotection, and
      neuroregeneration. It is a model of occlusion of small cerebral vessels, which
      provides detailed study of molecular mechanisms of ischemic cell death and useful
      for search of potential anti-stroke agents. Its advantages include well-defined
      location and size of ischemic lesion that are determined by the aiming of the
      laser beam at the predetermined brain region; easy impact dosing by changing
      light intensity and duration; low invasiveness and minimal surgical intervention
      without craniotomy and mechanical manipulations with blood vessel, which carry
      the risk of brain trauma; low animal mortality and prolonged sensorimotor
      impairment that provide long-term study of stroke consequences including behavior
      impairment and recovery; independence on genetic variations of blood pressure and
      vascular architecture; and high reproducibility. This review describes the
      current application of the photothrombotic stroke model for the study of cellular
      and molecular mechanisms of stroke development and ischemic penumbra formation,
      as well as for the search of anti-stroke drugs.

PMID- 29188435
TI  - Antibody-Drug Conjugates: Pharmacokinetic/Pharmacodynamic Modeling, Preclinical
      Characterization, Clinical Studies, and Lessons Learned.
AB  - Antibody-drug conjugates are an emerging class of biopharmaceuticals changing the
      landscape of targeted chemotherapy. These conjugates combine the target
      specificity of monoclonal antibodies with the anti-cancer activity of small
      molecule therapeutics. Several antibody-drug conjugates have received approval
      for the treatment of various types of cancer including gemtuzumab ozogamicin
      (Mylotarg(r)), brentuximab vedotin (Adcetris(r)), trastuzumab emtansine
      (Kadcyla(r)), and inotuzumab ozogamicin, which recently received approval
      (Besponsa(r)). In addition to these approved therapies, there are many antibody
      drug conjugates in the drug development pipeline and in clinical trials, although
      these fall outside the scope of this article. Understanding the pharmacokinetics
      and pharmacodynamics of antibody-drug conjugates and the development of
      pharmacokinetic/pharmacodynamic models is indispensable, albeit challenging as
      there are many parameters to incorporate including the disposition of the intact
      antibody-drug conjugate complex, the antibody, and the drug agents following
      their dissociation in the body. In this review, we discuss how antibody-drug
      conjugates progressed over time, the challenges in their development, and how our
      understanding of their pharmacokinetics/pharmacodynamics led to greater strides
      towards successful targeted therapy programs.

PMID- 29188436
TI  - Epithelial separation theory for post-tonsillectomy secondary hemorrhage:
      evidence in a mouse model and potential heparin-binding epidermal growth factor
      like growth factor therapy.
AB  - OBJECTIVE: To provide histological evidence to investigate a theory for post
      tonsillectomy secondary hemorrhage (PTH) in a mouse model and to evaluate the
      potential for heparin-binding epidermal growth factor-like growth factor (HB-EGF)
      treatment on wound healing in this model. METHODS: A prospective randomized
      single-blinded cohort study. A uniform tongue wound was created in 84 mice (day
      0). Mice were randomized to HB-EGF (treatment, n = 42) or saline (control, n =
      42). In treatment mice, HB-EGF 5 ug/ml was administered intramuscularly into the
      wound daily (days 0-14). In control mice, normal saline was administered daily.
      Three mice from each group were sacrificed daily through day 14 and the wounds
      evaluated histologically by blinded reviewers. RESULTS: Key stages of wound
      healing, including keratinocyte proliferation and migration, wound contraction,
      epithelial separation, and neoangiogenesis, are defined with implications for
      post-tonsillectomy wound healing. Epithelial separation (59 vs. 100%, p = 0.003)
      and wound reopening (8 vs. 48%, p < 0.001) were reduced with HB-EGF. Epithelial
      thickness (220 vs. 30 um, p = 0.04) was greater with HB-EGF. Wound closure (days
      4-5 vs. day 6, p = 0.01) occurred earlier with HB-EGF. CONCLUSIONS: In healing of
      oral keratinocytes on muscle epithelial separation secondary to muscle,
      contraction occurs concurrently with neoangiogenesis in the base of the wound,
      increasing the risk of hemorrhage. This potentially explains why post
      tonsillectomy secondary hemorrhage occurs and its timing. HB-EGF-treated wounds
      showed greater epithelial thickness, less frequent epithelial separation and
      wound reopening, and earlier wound closure prior to neovascularization,
      suggesting that HB-EGF may be a potential preventative therapy for PTH. LEVEL OF
      EVIDENCE: NA-animal studies or basic research.

PMID- 29188437
TI  - Nasopharyngeal carcinoma: relationship between invasion of the prevertebral space
      and distant metastases.
AB  - PURPOSE: To identify primary sites of nasopharyngeal carcinoma (NPC) invasion on
      the staging head and neck magnetic resonance imaging (MRI) that correlate with
      distant metastases (DM). MATERIALS AND METHODS: Staging head and neck MRI
      examinations of 579 NPC patients were assessed for primary tumour invasion into
      16 individual sites, primary stage (T) and nodal stage (N). Results were
      correlated with distant metastasis-free survival (DMFS) using the Cox regression,
      and the diagnostic performance of significant independent markers for DM was
      calculated. In addition, sites of primary tumour invasion were correlated also
      with involvement of the first echelon of ipsilateral nodes (FEN+) using logistic
      regression. RESULTS: Distant metastases were present in 128/579 NPC patients
      (22.1%) after intensity-modulated radiotherapy (IMRT)/chemo-IMRT and 5-year DMFS
      was 78.8%. Prevertebral space invasion (PVS+) and N stage, but not T stage, were
      independent prognostic markers of DMFS (p = 0.016, < 0.001, and 0.433,
      respectively). Compared to stage N3, PVS invasion had a higher sensitivity (28.1
      vs. 68.8%), but lower specificity (90.5 vs. 47.4%) and accuracy (76.7 vs. 48.9%)
      for correlating patients with DM. PVS invasion, together with parapharyngeal fat
      space invasion (PPFS+), was also an independent predictive marker of FEN+.
      CONCLUSION: PVS was the only site of primary tumour invasion that independently
      correlated with DM, and together with PPFS + was an independent prognostic marker
      of FEN+, but the low specificity and accuracy of PVS invasion limits its use as a
      prognostic marker of DM.

PMID- 29188440
TI  - Minimizing irrigation water demand: An evaluation of shifting planting dates in
      Sri Lanka.
AB  - Climate change coupled with increasing demands for water necessitates an improved
      understanding of the water-food nexus at a scale local enough to inform farmer
      adaptations. Such assessments are particularly important for nations with
      significant small-scale farming and high spatial variability in climate, such as
      Sri Lanka. By comparing historical patterns of irrigation water requirements
      (IWRs) to rice planting records, we estimate that shifting rice planting dates to
      earlier in the season could yield water savings of up to 6%. Our findings
      demonstrate the potential of low-cost adaptation strategies to help meet crop
      production demands in water-scarce environments. This local-scale assessment of
      IWRs in Sri Lanka highlights the value of using historical data to inform
      agricultural management of water resources when high-skilled forecasts are not
      available. Given national policies prioritizing in-country production and
      farmers' sensitivities to water stress, decision-makers should consider local
      degrees of climate variability in institutional design of irrigation management
      structures.

PMID- 29188438
TI  - Mapping causal mutations by exome sequencing in a wheat TILLING population: a
      tall mutant case study.
AB  - Forward genetic screens of induced mutant plant populations are powerful tools to
      identify genes underlying phenotypes of interest. Using traditional techniques,
      mapping causative mutations from forward screens is a lengthy, multi-step
      process, requiring the identification of a broad genetic region followed by
      candidate gene sequencing to characterize the causal variant. Mapping by whole
      genome sequencing accelerates the identification of causal mutations by
      simultaneously defining a mapping region and providing information on the induced
      genetic variants. In wheat, although the availability of a high-quality draft
      genome assembly facilitates mapping and mutation calling, whole genome
      resequencing remains prohibitively expensive due to its large genome. In the
      current study, we used exome sequencing as a complexity reduction strategy to
      detect mutations associated with a target phenotype. In a segregating wheat EMS
      population, we identified a clear peak region on chromosome arm 4BS associated
      with increased plant height. Although none of the significant SNPs seemed
      causative for the mutant phenotype, they were sufficient to identify a linked ~
      1.9 Mb deletion encompassing nine genes. These genes included Rht-B1, which is
      known to have a strong effect on plant height and is a strong candidate for the
      observed phenotype. We performed simulation experiments to determine the impacts
      of sequencing depth and bulk size and discuss the importance of considering each
      factor when designing mapping-by-sequencing experiments in wheat. This approach
      can accelerate the identification of candidate causal point mutations or linked
      deletions underlying important phenotypes.

PMID- 29188439
TI  - A Fully-Closed and Automated Hollow Fiber Bioreactor for Clinical-Grade
      Manufacturing of Human Mesenchymal Stem/Stromal Cells.

PMID- 29188441
TI  - Vulnerability of Canadian aquatic ecosystems to nuclear accidents.
AB  - Several cesium and strontium bioaccumulation models are used widely in national
      and international guidance for ecological and human health risk assessments for
      radiocesium (134Cs and 137Cs) and radiostrontium (90Sr), but have not been used
      to make predictions of radiological risk from nuclear accidents under variable
      environmental conditions on broad geographical scales. In this paper, we first
      present models for predicting the bioaccumulation of cesium and strontium by
      aquatic biota based on ambient concentrations of dissolved potassium and calcium,
      respectively, and then test these models using independent data from aquatic
      ecosystems at Canadian nuclear sites. Secondly, models yielding the best
      predictions across a wide range of input parameters were selected to estimate
      bioaccumulation factors (BAFs) for cesium and strontium in aquatic ecosystems
      across Canada, using trophic level of organisms and dissolved potassium for
      cesium and calcium concentrations for strontium as predictor variables, and
      presented as contour maps of radiological risk. The models show that risk from
      bioaccumulation of cesium and strontium can vary by several orders of magnitude
      depending on site-specific environmental conditions and trophic ecology. Overall,
      our results suggest that single-parameter approaches taken by regulatory
      standards may either over- or under-predict radiological risk at many locations,
      and are thus not readily suitable to inform siting decisions for new nuclear
      developments.

PMID- 29188442
TI  - Categorizing coordination from the perception of joint actions.
AB  - The ability to perceive others' actions and coordinate our own body movements
      accordingly is essential for humans to interact with the social world. However,
      it is still unclear how the visual system achieves the remarkable feat of
      identifying temporally coordinated joint actions between individuals.
      Specifically, do humans rely on certain visual features of coordinated movements
      to facilitate the detection of meaningful interactivity? To address this
      question, participants viewed short video sequences of two actors performing
      different joint actions, such as handshakes, high fives, etc. Temporal
      misalignments were introduced to shift one actor's movements forward or backward
      in time relative to the partner actor. Participants rated the degree of
      interactivity for the temporally shifted joint actions. The impact of temporal
      offsets on human interactivity ratings varied for different types of joint
      actions. Based on human rating distributions, we used a probabilistic cluster
      model to infer latent categories, each revealing shared characteristics of
      coordinated movements among sets of joint actions. Further analysis on the
      clustered structure suggested that global motion synchrony, spatial proximity
      between actors, and highly salient moments of interpersonal coordination are
      critical features that impact judgments of interactivity.

PMID- 29188443
TI  - Cannibalism amongst penitentiary escapees from Sarah Island in nineteenth century
      Van Diemen's Land.
AB  - Alexander Pearce was an Irish convict incarcerated on Sarah Island on the west
      coast of Van Diemen's Land (modern day Tasmania, Australia) in 1822, following
      his transportation to the colony from the United Kingdom for seven years in 1819.
      On two occasions he escaped from the island, in September 1822 and again in
      November 1823, and was only able to survive the harsh conditions by killing and
      consuming his fellow escapees. Given that Pearce utilized the only sustenance
      that was at hand (i.e. his five companions), and that there was a temporal
      separation between the two episodes, this may represent a separate category of
      anthropophagy, that of serial opportunistic cannibalism.

PMID- 29188444
TI  - ESCAP for mental health of child and adolescent refugees: facing the challenge
      together, reducing risk, and promoting healthy development.

PMID- 29188445
TI  - Childhood physical maltreatment, perceived social isolation, and internalizing
      symptoms: a longitudinal, three-wave, population-based study.
AB  - A number of cross-sectional studies have consistently shown a correlation between
      childhood physical maltreatment, perceived social isolation and internalizing
      symptoms. Using a longitudinal, three-wave design, this study sought to assess
      the mediating role of perceived social isolation in adulthood in the association
      between childhood physical maltreatment and internalizing symptoms in adulthood.
      The study has a three-wave design. We used data collected from 1994 to 2008
      within the framework of the Tromso Study (N = 4530), a representative prospective
      cohort study of men and women. Perceived social isolation was measured at a mean
      age of 54.7 years, and internalizing symptoms were measured at a mean age of 61.7
      years. The difference-in-coefficients method was used to assess the indirect
      effects and the proportion (%) of mediated effects. Childhood physical
      maltreatment was associated with an up to 68% [relative risk (RR) = 1.68, 95%
      confidence interval (CI): 1.33-2.13] higher risk of perceived social isolation in
      adulthood. Childhood physical maltreatment and perceived social isolation in
      adulthood were associated with greater levels of internalizing symptoms in
      adulthood (p < 0.01). A dose-response association was observed between childhood
      physical maltreatment and internalizing symptoms in adulthood (p < 0.001).
      Perceived social isolation in adulthood mediated up to 14.89% (p < 0.05) of the
      association between childhood physical maltreatment and internalizing symptoms in
      adulthood. The results of this study indicate the need to take perceived social
      isolation into account when considering the impact of childhood physical
      maltreatment on internalizing symptoms.

PMID- 29188446
TI  - iCHRCloud: Web & Mobile based Child Health Imprints for Smart Healthcare.
AB  - Reducing child mortality with quality care is the prime-most concern of all
      nations. Thus in current IT era, our healthcare industry needs to focus on
      adapting information technology in healthcare services. Barring few preliminary
      attempts to digitalize basic hospital administrative and clinical functions, even
      today in India, child health and vaccination records are still maintained as
      paper-based records. Also, error in manually plotting the parameters in growth
      charts results in missed opportunities for early detection of growth disorders in
      children. To address these concerns, we present India's first hospital linked,
      affordable automated vaccination and real-time child's growth monitoring cloud
      based application- Integrated Child Health Record cloud (iCHRcloud). This
      application is based on HL7 protocol enabling integration with hospital's HIS/EMR
      system. It provides Java (Enterprise Service Bus and Hibernate) based web portal
      for doctors and mobile application for parents, enhancing doctor-parent
      engagement. It leverages highchart to automate chart preparation and provides
      access of data via Push Notification (GCM and APNS) to parents on iOS and Android
      mobile platforms. iCHRcloud has also been recognized as one of the best
      innovative solution in three nationwide challenges, 2016 in India. iCHRcloud
      offers a seamless, secure (256 bit HTTPS) and sustainable solution to reduce
      child mortality. Detail analysis on preliminary data of 16,490 child health
      records highlight the diversified need of various demographic regions. Thus,
      primary lesson would be to implement better validation strategies to fulfill the
      customize requisites of entire population. This paper presents first glimpse of
      data and power of the analytics in policy framework.

PMID- 29188447
TI  - Procrastination in the pigeon: Can conditioned reinforcement increase the
      likelihood of human procrastination?
AB  - Procrastination is the tendency to put off initiation or completion of a task.
      Although people are typically known to procrastinate, recent research suggests
      that they sometimes "pre-crastinate" by initiating a task sooner than they need
      to (Rosenbaum et al. in Psychological Science, 25(7), 1487-1496, 2014). A similar
      finding of precrastination was reported by Wasserman and Brzykcy (Psychonomic
      Bulletin & Review, 22, 1130-1134, 2015) with pigeons using a somewhat different
      procedure. In the present experiment, we used a procedure with pigeons that was
      more similar to the procedure used by Rosenbaum et al. Pigeons were given a
      choice between two sequences of events (concurrent chains). Choice of the
      procrastination chain resulted in color A, which 15-s later would change to color
      B and 5-s later resulted in reinforcement. Choice of the precrastination chain
      resulted in color C, which 5-s later would change to color D and 15-s later
      resulted in reinforcement. Thus, both chains led to reinforcement after 20 s.
      Results indicated that the pigeons procrastinated. That is, they preferred the 15
      5 chain over the 5-15 chain. The results are consistent with Fantino's (Journal
      of the Experimental Analysis of Behavior, 12, 723-730, 1969) delay reduction
      theory, which posits that stimuli that signal a reduction in the delay to
      reinforcement, such as the 5-s stimulus that occurred immediately prior to
      reinforcement, serve as strong conditioned reinforcers and should be preferred.
      In support of this theory, the pigeons pecked most at the 5-s stimulus that led
      immediately to reinforcement, indicating that it had become a strong conditioned
      reinforcer. The results suggest that delay reduction theory, a theory that
      emphasizes the attraction to stimuli that predict reinforcement with a short
      delay, also may contribute to human procrastination behavior because when task
      completion comes just before the deadline, it may become a stronger conditioned
      reinforcer than if task completion comes earlier.

PMID- 29188448
TI  - Controlled information processing, automaticity, and the burden of proof.
AB  - Cognitive psychologists often distinguish between voluntary and
      involuntary/automatic processes in attention and cognitive control. Dedicated
      experimental paradigms have been developed to isolate involuntary information
      processing, but these paradigms tend to assume a rigid and inflexible process
      that is either stimulus-driven or built up through simple repetition. In
      contrast, voluntary information processing is often assumed when processing is in
      line with arbitrarily defined task-specific goals. Here I review evidence from
      multiple cases suggesting that ostensibly goal-directed cognitive processes may
      not be so voluntary and controlled. It is argued that automatic processes can be
      conditionalized to reflect the task relevance of the stimuli and selection
      history in a variety of ways, rapidly and flexibly adjusting in order to
      facilitate future goal-directed behavior. As a result, many studies assumed to
      have measured a voluntary cognitive process have likely measured an amalgam of
      voluntary and automatic processes, thus blurring the distinction between the two.
      Automaticity may be much broader and more sophisticated than has previously been
      thought, which has wide-reaching implications for our conception of human
      cognitive control.

PMID- 29188450
TI  - Ankle muscle activity modulation during single-leg stance differs between
      children, young adults and seniors.
AB  - PURPOSE: Incomplete maturation and aging-induced declines of the neuromuscular
      system affect postural control both in children and older adults and lead to high
      fall rates. Age-specific comparisons of the modulation of ankle muscle activation
      and behavioral center of pressure (COP) indices during upright stance have been
      rarely conducted. The objective of the present study was to quantify aging
      effects on a neuromuscular level. Thus, surface electromyography (SEMG)
      modulation and co-activity of ankle muscles during single-leg standing was
      compared in healthy children, young adults and seniors. METHODS: Postural
      steadiness (velocity and mean sway frequency of COP), relative muscle activation
      (SEMG modulation) and co-activation of two ankle muscles (tibialis anterior, TA;
      soleus, SO) were examined during single-leg stance in 19 children [age, 9.7 (SD
      0.5) years], 30 adults [23.3 (1.5) years] and 29 seniors [62.7 (6.1) years].
      RESULTS: Velocity of COP in medio-lateral and anterior-posterior directions, mean
      sway frequency in anterior-posterior direction, relative muscle activation (TA
      and SO) and co-activation revealed large age effects (P < 0.003, eta p2 > 0.14).
      Post-hoc comparisons indicated higher COP velocities, anterior-posterior
      frequencies, relative SO activation and co-activation in children and seniors
      when compared with adults. Relative TA activation was higher in children and
      adults compared with seniors (P < 0.001). CONCLUSIONS: Increased postural sway in
      children and seniors seems to be counteracted with higher TA/SO co-activity and
      SO modulation. However, TA modulation is higher in children and adults, whereas
      seniors' TA modulation capacity is diminished. An aging-induced decline of TA
      motor units might account for deteriorations of TA modulation in seniors.

PMID- 29188449
TI  - Current and New Therapeutic Strategies for Relapsed and Refractory Multiple
      Myeloma: An Update.
AB  - Although survival of multiple myeloma patients has at least doubled during recent
      years, most patients eventually relapse, and treatment at this stage may be
      particularly complex. At the time of relapse, the use of alternative drugs to
      those given upfront is current practice. However, many new options are currently
      available for the treatment of relapsed multiple myeloma, including recently
      approved drugs, such as the second- and third-generation proteasome inhibitors
      carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal
      antibodies daratumumab and elotuzumab and the histone deacetylase inhibitor
      panobinostat, but also new targeted agents are under active investigation (e.g.
      signal transduction modulators, kinesin spindle protein inhibitors, and
      inhibitors of NF-kB, MAPK, AKT). We here describe a new paradigm for the
      treatment of relapsed multiple myeloma. The final goal should be finding a
      balance among efficacy, toxicity, and cost and, at the end of the road, achieving
      long-lasting control of the disease and eventually even cure in a subset of
      patients.

PMID- 29188451
TI  - Pediatric cleft palate patients show a 3- to 5-fold increase in cumulative
      radiation exposure from dental radiology compared with an age- and gender-matched
      population: a retrospective cohort study.
AB  - OBJECTIVE: The objective of the study was to compare estimates of pediatric
      cumulative exposure and lifetime attributable risk (LAR) of radiation-induced
      cancer from dental radiology between cleft palate (CP) subjects and age- and
      gender-matched controls (non-CP), with and without orthodontic treatment.
      MATERIALS AND METHODS: The radiation exposure frequency of CP subjects and non-CP
      controls with and without orthodontic treatment was compared for two-dimensional
      radiography (intra-oral, panoramic and cephalometric radiography), computed
      tomography (CT), and cone-beam CT (CBCT) using cumulative radiation dose as an
      estimate. From this dose estimate, the age- and gender-dependent risk for
      radiation-induced stochastic effects was calculated for each patient group.
      RESULTS: CP patients received more radiographic examinations than non-CP
      controls, with the exception of intra-oral radiographs. The cumulative dose to CP
      patients was considerably higher (1963 MUSv at the age of 20 years) than non-CP
      patients with (597 MUSv) and without (383 MUSv) orthodontic treatment, primarily
      due to the higher frequency of CT scanning. Accordingly, CP patients had a three
      to five times higher LAR than non-CP patients. CONCLUSIONS: This study suggests a
      significantly higher lifetime radiation exposure to CP patients than non-CP
      controls from dental radiographic procedures. Diagnostic benefits from the use of
      CT and CBCT in children must be justified and appropriate dose optimization
      strategies implemented. CLINICAL RELEVANCE: The present study indicates the need
      for proper justification and optimization of pediatric exposures in dentistry,
      with a special focus on high-risk groups.

PMID- 29188452
TI  - Bisphosphonates hinder osteoblastic/osteoclastic differentiation in the maxillary
      sinus mucosa-derived stem cells.
AB  - OBJECTIVES: Although bisphosphonates (BPs) are known to be associated with
      osteonecrosis of the maxilla, the precise effects of BPs on bone metabolism in
      human maxillary sinus mucosal cells (HMSMCs) are not yet known. The purposes of
      this study were to examine the effects of the BPs zoledronate (ZOL) and
      alendronate (ALN) on osteoblastic and osteoclastic differentiation in HMSMCs and
      to investigate the signaling pathways involved. MATERIALS AND METHODS: The
      effects of ZOL and ALN were assessed for osteoblast differentiation by alkaline
      phosphatase (ALP) activity, alizarin red staining, and RT-PCR for genes encoding
      Runx2 and osterix. Receptor activator of nuclear factor-kappaB ligand (RANKL)
      mediated osteoclast differentiation in bone marrow macrophages (BMMs) was also
      examined. RESULTS: ZOL and ALN both suppressed osteoblastic differentiation, as
      evidenced by their effects on ALP activity, mineralization nodule formation, and
      the mRNA expression levels of osteoblastic transcript factors. The
      RANKL/osteoprotegerin ratio in HMSMCs was increased by ALN, whereas ZOL had the
      opposite effect. Conditioned medium obtained from ALN-treated HMSMCs stimulated
      osteoclast formation and upregulated NFATc1 expression, whereas conditioned
      medium from ZOL-treated cells did not. ALN was more cytotoxic and stimulated
      apoptosis more strongly than ZOL. BPs decreased the protein levels of the non
      canonical Wnt signaling protein Wnt5a and calmodulin-dependent kinase II.
      Moreover, recombinant human Wnt5a reversed the effects of BPs on osteoblastic and
      osteoclastic differentiation. CONCLUSION: This study is the first demonstration
      that BPs exert negative effects on osteoblastic and osteoclastic processes via
      the non-canonical Wnt pathway in HMSMSCs. CLINICAL RELEVANCE: It suggests that
      patients taking BPs during the period of maxillary sinus lifting and amentation
      should be given special attention.

PMID- 29188453
TI  - Can the combination of laparoscopy and enhanced recovery improve long-term
      survival after elective colorectal cancer surgery?
AB  - AIM: Enhanced recovery after surgery (ERAS) programmes and laparoscopic
      techniques both provide short-term benefits to patients undergoing colorectal
      cancer surgery. ERAS protocol compliance may improve long-term survival in those
      undergoing open colorectal resection but as laparoscopic data has not been
      reported. Therefore, we aimed to investigate the impact of the combination of
      laparoscopy and ERAS management on 5-year overall survival. METHODS: A dedicated
      prospectively populated colorectal cancer surgery database was reviewed. Patient
      inclusion criteria were biopsy-proven colorectal adenocarcinoma, undergoing
      elective surgery undertaken with curative intent. All patients were managed
      within an established ERAS programme and routinely followed up for 5 years.
      Overall survival was measured using the log-rank Kaplan-Meier method at 5 years.
      RESULTS: Eight hundred fifty-four patients met the inclusion criteria. Four
      hundred eighty-one (56%) cases were laparoscopic with 98 patients (20%) requiring
      conversion. There were no differences in patient or tumour demographics between
      the surgical groups. Median ERAS protocol compliance was 93% (range 53-100%).
      Five-year overall survival was superior in laparoscopic cases compared with that
      of converted and open surgery (78 vs 68 vs 70%, respectively, p < 0.007). An open
      approach (HR 1.55, 95%CI 1.16-2.06, p = 0.002) and delayed hospital discharge (>
      7 days, HR 1.5, 95%CI 1.13-1.9, p = 0.003) were the only modifiable risk factors
      associated with poor survival. CONCLUSIONS: The use of a laparoscopic approach
      with enhanced recovery after surgery management appears to have long-term
      survival benefits following colorectal cancer resection.

PMID- 29188454
TI  - A narrative review of the impact of interventions in acute kidney injury.
AB  - Acute kidney injury (AKI) is independently associated with significant morbidity
      and mortality, and is thus an important challenge facing physicians in modern
      healthcare. This narrative review assesses the impact of strategies employed to
      tackle AKI following the 2009 NCEPOD report on acute kidney injury (Sterwart et
      al. Acute kidney injury: adding insult to injury, pp 1-22, 2009). There is scarce
      and heterogeneous research into hard end points such as mortality and AKI
      progression for AKI interventions. This review found that e-alerts have varying
      effects on mortality and AKI progression, but decrease the incidence of contrast
      induced AKI. The use of AKI bundles delivers statistically significant
      improvements in mortality and AKI progression. Similarly, AKI nurses generate
      statistically significant improvements on hospital acquired AKI and mortality. As
      yet there is no evidence base for the effects of education, sick day rules and
      smart phone apps. Overall, a combination of e-alerts and AKI bundles supported by
      education yielded the most effective and statistically significant results.
      Current practice revolves around reactive rather than preventative behaviour.
      This narrative review discusses reactive interventions and their impact on the
      progression and severity of AKI, and on mortality from it. Preventative
      behaviour, such as risk stratification and early intervention in the
      deteriorating patient, may be influential in decreasing AKI incidence.

PMID- 29188455
TI  - The Role of Cardiologists in the Management of Patients with Heart Failure.
AB  - Heart failure is a complex clinical syndrome with a remarkable impact on health
      care systems in terms of patients' morbidity and mortality, as well as direct and
      indirect costs. It is essential to redesign models of care for patients with
      heart failure that are tailored on personalized health care needs and carried out
      in the most appropriate setting. There is some debate about the role of
      cardiologists in the management of patients with heart failure. Indeed, results
      regarding the inclination of cardiologists' patients to achieve better outcomes
      are controversial, given the heterogeneity of studies in terms of study design,
      population, setting and variables considered. The aim of this chapter is to
      describe and synthesize the current state of knowledge about the role of
      specialists in the management of patient with heart failure, and to assess
      whether there is a type of patients for which cardiologists demonstrate the
      greatest value or a setting of care where they add more benefit.

PMID- 29188457
TI  - Can the ability to adapt to exercise be considered a talent-and if so, can we
      test for it?
AB  - Talent identification (TI) is a popular and hugely important topic within sports
      performance, with an ever-increasing amount of resources dedicated to unveiling
      the next sporting star. However, at present, most TI processes appear to select
      high-performing individuals at the present point in time, as opposed to
      identifying those individuals with the greatest capacity to improve. This
      represents a potential inefficiency within the TI process, reducing its
      effectiveness. In this article, we discuss whether the ability to adapt
      favorably, and with a large magnitude, to physical training can be considered a
      talent, testing it against proposed criteria. We also discuss whether, if such an
      ability can be considered a talent, being able to test for it as part of the TI
      process would be advantageous. Given that such a capacity is partially heritable,
      driven by genetic variation between individuals that mediate the adaptive
      response, we also explore whether the information gained from genetic profiling
      can be used to identify those with the greatest capacity to improve. Although
      there are some ethical hurdles which must be considered, the use of genetic
      information to identify those individuals with the greatest capacity appears to
      hold promise and may improve both the efficiency and effectiveness of
      contemporary TI programmes.

PMID- 29188456
TI  - Prophylactic effect of neoadjuvant chemotherapy in gastric cancer patients with
      postoperative complications.
AB  - BACKGROUND: The occurrence of postoperative complications may have a significant
      negative impact on the prognosis of patients with gastrointestinal cancers. The
      inflammatory response releases systemic cytokines, which may induce residual
      cancer cell growth. Recently, neoadjuvant chemotherapy (NAC) was found to improve
      the prognosis of advanced gastric cancer (GC). We hypothesize that when
      postoperative complications occur after gastrectomy, NAC treatment of
      micrometastases can prevent residual cancer cell growth. METHODS: This study
      included 101 patients who underwent curative resection after NAC for GC from 2005
      to 2015. Clinical data, including intraoperative parameters, were collected
      retrospectively. Overall survival (OS) and relapse-free survival (RFS) were
      compared between the patients with complications and those without complications.
      RESULTS: Of the 101 patients, 35 (34.7%) had grade 2 or higher complications.
      Among those with complications, the 3- and 5-year OS rates were 63.5 and 58.2%
      and the 3- and 5-year RFS rates 41.7 and 41.7%, respectively. Among those without
      complications, the 3- and 5-year OS rates were 65.9 and 56.3% and the 3- and 5
      year RFS rates 51.1 and 43.9%, respectively. There was no significant difference
      in prognosis between the patients with complications and those without
      complications. CONCLUSION: Our study is the first to demonstrate the potential of
      NAC to abolish the poor prognosis induced by postoperative complications after
      curative resection for GC.

PMID- 29188458
TI  - Single soliton solution to the extended KdV equation over uneven depth.
AB  - In this note we look at the influence of a shallow, uneven riverbed on a soliton.
      The idea consists in an approximate transformation of the equation governing wave
      motion over an uneven bottom to an equation for a flat one for which the exact
      solution exists. The calculation is one space dimensional, and so corresponds to
      long trenches or banks under wide rivers or oceans.

PMID- 29188459
TI  - Petri dish versus Winogradsky column: a longue duree perspective on purity and
      diversity in microbiology, 1880s-1980s.
AB  - Microbial diversity has become a leitmotiv of contemporary microbiology, as
      epitomized in the concept of the microbiome, with significant consequences for
      the classification of microbes. In this paper, I contrast microbiology's current
      diversity ideal with its influential predecessor in the twentieth century, that
      of purity, as epitomized in Robert Koch's bacteriological culture methods. Purity
      and diversity, the two polar opposites with regard to making sense of the
      microbial world, have been operationalized in microbiological practice by tools
      such as the "clean" Petri dish versus the "dirty" Winogradsky column, the latter
      a container that mimics, in the laboratory, the natural environment that teems
      with diverse microbial life. By tracing the impact of the practices and concepts
      of purity and diversity on microbial classification through a history of
      techniques, tools, and manuals, I show the shifts in these concepts over the last
      century. Juxtaposing the dominant purity ideal with the more restricted, but
      continuously articulated, diversity ideal in microbial ecology not only provides
      a fresh perspective on microbial classification that goes beyond its intellectual
      history, but also contextualizes the present focus on diversity. By covering the
      period of a century, this paper outlines a revised longue duree historiography
      that takes its inspiration from artifacts, such as Petri dish and the Winogradsky
      column, and thereby simple, but influential technologies that often remain
      invisible. This enables the problem of historical continuity in modern science to
      be addressed and the accelerationist narratives of its development to be
      countered.

PMID- 29188460
TI  - Development of a model of three-dimensional imaging for the preoperative planning
      of TaTME.

PMID- 29188461
TI  - Variability in the phytoplankton community of Kavaratti reef ecosystem (northern
      Indian Ocean) during peak and waning periods of El Nino 2016.
AB  - El Nino, an interannual climate event characterized by elevated oceanic
      temperature, is a prime threat for coral reef ecosystems worldwide, owing to
      their thermal threshold sensitivity. Phytoplankton plays a crucial role in the
      sustenance of reef trophodynamics. The cell size of the phytoplankton forms the
      "master morphological trait" with implications for growth, resource acquisition,
      and adaptability to nutrients. In the context of a strong El Nino prediction for
      2015-2016, the present study was undertaken to evaluate the variations in the
      size-structured phytoplankton of Kavaratti reef waters, a major coral atoll along
      the southeast coast of India. The present study witnessed a remarkable change in
      the physicochemical environment of the reef water and massive coral bleaching
      with the progression of El Nino 2015-2016 from its peak to waning phase. The
      fluctuations observed in sea surface temperature, pH, and nutrient concentration
      of the reef water with the El Nino progression resulted in a remarkable shift in
      phytoplankton size structure, abundance, and community composition of the reef
      waters. Though low nutrient concentration of the waning phase resulted in lower
      phytoplankton biomass and abundance, the diazotroph Trichodesmium erythraeum
      predominated the reef waters, owing to its capability of the atmospheric nitrogen
      fixation and dissolved organic phosphate utilization.

PMID- 29188463
TI  - Evaluation of anterior chamber parameters with spectral-domain optical coherence
      tomography.
AB  - PURPOSE: To evaluate several anterior chamber parameters in healthy young adults
      using spectral-domain optical coherence tomography and to describe the
      repeatability and reproducibility of this method. STUDY DESIGN: Prospective
      clinical study. METHODS: Fifty-two eyes of 52 healthy volunteers were enrolled.
      Manual measurements of the anterior chamber angle (ACA500 and ACA750), angle
      opening distance (AOD500 and AOD750), angle-to-angle distance (ATA), anterior
      chamber width (ACW), and lens vault (LV) were obtained. RESULTS: The mean nasal
      ACA500 was 44.87 +/- 12.92 degrees ; ACA750, 43.94 +/- 10.41 degrees ; AOD500,
      672.54 +/- 270.19 um; AOD750, 881.87 +/- 290.55 um. The mean temporal ACA500 was
      41.46 +/- 11.20 degrees ; ACA750, 41.27 +/- 11.31 degrees ; AOD500, 603.15 +/-
      232.28 um; AOD750, 823.46 +/- 308.76 um. The differences between the
      corresponding nasal and temporal parameters were statistically significant. The
      ACW was 11.97 +/- 0.42 mm, the ATA was 12.10 +/- 0.43 mm, and the LV was 3.71 +/-
      232.93 um. The ACA was highly associated with the LV. The intraclass correlation
      coefficients ranged from 0.984 to 0.999 for the intraobserver repeatability and
      from 0.966 to 0.998 for the interobserver reproducibility. CONCLUSIONS: This
      study assessed anterior chamber parameters in healthy young adults using spectral
      domain optical coherence tomography. This technique reveals the spatial
      relationships of the ocular structures, provides high-resolution images, and
      results in high degrees of intraobserver and interobserver repeatabilities.

PMID- 29188462
TI  - Quantification of retinal changes after resolution of submacular hemorrhage
      secondary to polypoidal choroidal vasculopathy.
AB  - PURPOSE: To evaluate changes in the thickness of retinal layers after resolution
      of submacular hemorrhage secondary to polypoidal choroidal vasculopathy (PCV).
      STUDY DESIGN: Retrospective, observational study. METHODS: This study included 21
      patients (21 eyes) who had been diagnosed with submacular hemorrhage secondary to
      PCV and treated using anti-vascular endothelial growth factor monotherapy. After
      the hemorrhage had resolved, the thicknesses of the retinal layers were measured
      on horizontal- and vertical-crosshair optical coherence tomography scan images.
      The thickness of each layer in the region affected by the hemorrhage was compared
      with the thickness of the layer in the corresponding region in the fellow eye, as
      well as between an unaffected region in the eye with the hemorrhage and the
      corresponding region in the fellow eye. RESULTS: Optical coherence tomography
      (OCT) was performed 5.5+/-2.8 months after diagnosis. In the horizontal OCT
      images, the outer plexiform layer (OPL) and outer nuclear layer (ONL) +
      photoreceptor layer (PRL) were significantly thinner in the affected region than
      in the corresponding region (P = 0.019 and P <0.001, respectively). In the
      vertical OCT image, the ONL+PRL was significantly thinner in the affected region
      than in the corresponding region (P <0.001). The thickness of the retinal layer
      in the unaffected region did not differ from that in the corresponding region of
      the fellow eye. CONCLUSIONS: The significant thinning of the outer retinal layers
      in the regions affected by submacular hemorrhage suggests that the hemorrhage
      induces marked damage in the outer retinal layers, explaining the poor visual
      prognosis of submacular hemorrhage.

PMID- 29188464
TI  - A Statewide Hospital-Based Safe Infant Sleep Initiative: Measurement of Parental
      Knowledge and Behavior.
AB  - Sleep-related infant deaths are a leading cause of infant mortality in Georgia,
      and these deaths are largely associated with unsafe sleep practices among
      caregivers. In early 2016, the Georgia Department of Public Health launched the
      Georgia Safe to Sleep Hospital Initiative, providing hospitals with safe infant
      sleep information and educational materials to be distributed to families and
      newborns. This study examined the knowledge and behaviors of a sample of Georgia
      parents after the implementation of the Hospital Initiative and identified the
      family characteristics and intervention components most closely associated with
      the knowledge and practice of safe infant sleep. The primary caretakers of all
      infants born in Georgia from August to October 2016 were invited to complete a
      web-based survey 1 month after hospital discharge. The final sample size included
      420 parents of newborns, and the primary outcomes assessed included two measures
      of knowledge and four measures of infant sleep behaviors regarding infant sleep
      position and location. Most respondents demonstrated knowledge of the correct
      recommended sleep position (90%) and location (85%). Logistic regression revealed
      that receipt of information in the hospital was significantly correlated with
      safe sleep behaviors, and infant sleep habits tended to influence safe sleep
      practices. Additionally, Medicaid parents receiving bassinets from the hospital
      were 74% less likely to bed share (OR 0.26; 95% CI 0.007). Implementation of a
      statewide hospital initiative was associated with high levels of parental
      knowledge and behavior and may have been successful in reducing the practice of
      bed sharing among Medicaid parents.

PMID- 29188465
TI  - Demographic and Travel Characteristics of Travel-Associated Zika Virus Infection
      Case-Patients in San Diego County, California (January 1, 2016-March 31, 2017).
AB  - Most Zika disease cases diagnosed in the continental US have been associated with
      travel to areas with risk of Zika transmission, mainly the Caribbean and Latin
      America. Limited information has been published about the demographic and travel
      characteristics of Zika case-patients in the United States, besides their age and
      gender. During 2016-2017 the County of San Diego Health and Human Services
      Agency, California, expanded the scope and completeness of demographic and travel
      information collected from Zika case-patients for public health surveillance
      purposes. The majority (53.8%) of travel-related Zika virus infection case
      patients (n = 78) in the county were Hispanic, significantly higher (p <= 0.05)
      than the 33.0% of Hispanics in the county. Foreign-born residents, mainly from
      Mexico, were also overrepresented among cases compared to their share in the
      county population (33.3 vs. 23.0%; p <= 0.05). Seventeen (21.8%) patients
      reported a primary language other than English (14 Spanish). Most case-patients
      traveled for tourism (54%) or to visit friends and relatives (36%). This
      surveillance information helps identify higher-risk populations and implement
      culturally targeted interventions for Zika prevention and control.

PMID- 29188466
TI  - Neuronal avalanches: Where temporal complexity and criticality meet.
AB  - The model of the current paper is an extension of a previous publication, wherein
      we have used the leaky integrate-and-fire model on a regular lattice with
      periodic boundary conditions, and introduced the temporal complexity as a genuine
      signature of criticality. In that work, the power-law distribution of neural
      avalanches was a manifestation of supercriticality rather than criticality. Here,
      however, we show that the continuous solution of the model and replacing the
      stochastic noise with a Gaussian zero-mean noise leads to the coincidence of
      power-law display of temporal complexity, and spatiotemporal patterns of neural
      avalanches at the critical point. We conclude that the source of inconsistency
      may be a numerical artifact originated by the discrete description of the model
      which may imply a slow numerical convergence of the avalanche distribution
      compared to temporal complexity.

PMID- 29188467
TI  - Diagnosing tick-borne encephalitis: a re-evaluation of notified cases.
AB  - We set out to investigate the serological response of TBE virus (TBEV)-specific
      IgM and IgG antibodies in stored serum and cerebrospinal fluid (CSF) in notified
      TBE patients, in order to confirm or reject the diagnosis. We applied the ELISA
      methods used in clinical practice, Enzygnost and Immunozym, and assessed RT-PCR
      as a diagnostic tool. A total of 173 TBE cases were notified to the Public Health
      Agency. Samples from 129 patients were eligible for the study. Stored serum
      samples were found for 111 patients and CSF samples for 88 patients. All serum
      samples were analyzed with both Enzygnost and Immunozym, as well as an additional
      140 control samples. CSF samples, including samples from ten controls, were
      analyzed with Immunozym. RT-PCR for TBEV was performed on 126 serum, two whole
      blood, 96 CSF, two feces and four nasopharynx samples. Only two of 111 notified
      patients lacked detectable TBEV IgM in serum, from whom one sample was RT-PCR
      positive. According to the ECDC definition, 117/129 (90.7%) of the reported TBE
      cases were confirmed. Positive RT-PCR results were obtained in eight patients,
      one from whole blood and eight from serum samples. Four out of eight of the RT
      PCR positive patients were TBEV-IgM positive and none had detectable TBEV
      specific IgG. All of the tested CSF, feces and nasopharynx samples were RT-PCR
      negative. TBEV-specific IgG was detected in 88.4% and IgM in 31.6% of the CSF
      samples. RT-PCR on serum samples and CSF IgG antibodies can be used as
      complementary methods in TBE diagnostics, not least early in the disease course.

PMID- 29188468
TI  - The role of perceived threat during emergency department cardiac evaluation and
      the age-posttraumatic stress disorder link.
AB  - Evaluation for acute coronary syndrome (ACS) can trigger posttraumatic stress
      symptoms (PSS). Research suggests that younger, versus older, individuals may be
      at elevated risk for PSS after ACS evaluation. It has been proposed that younger
      individuals may be at greater risk because they perceive the suspected ACS event
      as more threatening than their older counterparts; however, this has yet to be
      tested. We examined whether perceived threat during ACS evaluation mediated the
      association between age and PSS after ACS evaluation in an observational cohort
      study of patients presenting to the emergency department (ED) with suspected ACS.
      Demographics and perceived threat were assessed in the ED. PSS were measured upon
      inpatient transfer or by phone 3 days later. The analytic sample comprised 871
      adult participants. Multiple linear regression was used to examine (1)
      associations of age and perceived threat with PSS and (2) whether perceived
      threat mediated the association. Bootstrapping with percentile-based confidence
      intervals (CIs) was used to test the indirect effect. Each year of age was
      associated with lower PSS (b = - 0.12, p < .001), independent of covariates.
      Older age was associated with lower perceived threat during ACS evaluation (b = -
      0.05, p < .001). Greater threat perceptions predicted greater PSS (b = 0.94, p <
      .0001). The indirect effect (- 0.04) was statistically significant (95% CI -
      0.07, - 0.02). Younger, versus older, individuals are at risk for greater PSS
      after ACS evaluation, and elevated perceived threat partially mediated this
      association. Understanding age differences in PSS development risk and the
      potential impact of age on threat perceptions may help inform ED treatment.

PMID- 29188469
TI  - MET-targeting antibody (emibetuzumab) and kinase inhibitor (merestinib) as single
      agent or in combination in a cancer model bearing MET exon 14 skipping.
AB  - Purpose Approximately 3% of lung cancer bears mutations leading to MET exon 14
      skipping, an oncogenic driver which is further evidenced by case reports of
      patient response to MET kinase inhibitor treatment. Approximately 15% of tumors
      harboring MET exon14 skipping have concurrent MET amplification. Experimental
      Design Merestinib is a type II MET kinase inhibitor. Emibetuzumab, a bivalent
      anti-MET antibody, internalizes MET receptor. Each single agent and the
      combination were evaluated in the Hs746t gastric cancer line bearing MET exon14
      skipping and MET amplification. Results Merestinib inhibited Hs746t cell
      proliferation (IC50=34 nM) and totally eliminated pMET at 100nM. Emibetuzumab
      showed little anti-proliferative activity against Hs746t cells (IC50>100nM), did
      not reduce pMET, and slightly reduced cell surface MET. In the Hs746t xenograft
      model, dose dependent differences in durability of response were seen with
      merestinib including durable tumor regression (91.8%) at 12 mg/kg qd.
      Emibetuzumab treatment (10mg/kg qw) provided transient tumor regression (37.7%),
      but tumors re-grew while on treatment. Concurrent combination of merestinib (6
      mg/kg qd) and emibetuzumab resulted in 85% tumor regression, while a sequential
      combination (initiating merestinib first) resulted in longer duration of
      treatment response. Conclusions Data in this study support a clinical evaluation
      of merestinib in patients with MET exon 14 skipping (NCT02920996). As a type II
      MET kinase inhibitor, merestinib may provide a therapeutic option to treatment
      naive patients or to patients who progress on type I MET inhibitor treatment.
      Data also support clinical evaluation of the sequential combination of merestinib
      with emibetuzumab when patients progress on single agent merestinib.

PMID- 29188470
TI  - Femtosecond laser-assisted cataract surgery with bimanual technique: learning
      curve for an experienced cataract surgeon.
AB  - PURPOSE: To describe the intraoperative complications and the learning curve of
      microincision cataract surgery assisted by femtosecond laser (FLACS) with
      bimanual technique performed by an experienced surgeon. METHODS: It is a
      prospective, observational, comparative case series. A total of 120 eyes which
      underwent bimanual FLACS by the same experienced surgeon during his first
      experience were included in the study; we considered the first 60 cases as Group
      A and the second 60 cases as Group B. In both groups, only nuclear sclerosis of
      grade 2 or 3 was included; an intraocular lens was implanted through a 1.4-mm
      incision. Best-corrected visual acuity (BCVA), surgically induced astigmatism
      (SIA), central corneal thickness and endothelial cell loss (ECL) were evaluated
      before and at 1 and 3 months after surgery. Intraoperative parameters, and intra-
      and post-operative complications were recorded. RESULTS: In Group A, we had
      femtosecond laser-related minor complications in 11 cases (18.3%) and post
      operative complications in 2 cases (3.3%); in Group B, we recorded 2 cases (3.3%)
      of femtosecond laser-related minor complications with no post-operative
      complications. Mean effective phaco time (EPT) was 5.32 +/- 3.68 s in Group A and
      4.34 +/- 2.39 s in Group B with a significant difference (p = 0.046). We recorded
      a significant mean BCVA improvement at 3 months in both groups (p < 0.05) and no
      significant SIA nor corneal pachymetry changes in the two groups during the
      follow-up (p > 0.05). Finally, we found significant ECL in both groups with a
      significant difference between the two groups (p = 0.042). CONCLUSIONS: FLACS
      with bimanual technique and low-energy LDV Z8 is associated with a necessary
      initial learning curve. After the first adjustments in the surgical technique,
      this technology seems to be safe and effective with rapid visual recovery and it
      helps surgeons to standardize the crucial steps of cataract surgery.

PMID- 29188471
TI  - Comparison of trypan blue and Brilliant Blue G for staining of the anterior lens
      capsule during cataract surgery: short-term results.
AB  - PURPOSE: The present study aimed to evaluate the potential corneal endothelial
      cell toxicity of trypan blue (TB) and Brilliant Blue G (BBG), two dyes used to
      stain the anterior capsule in cataract surgery. METHODS: We conducted a single
      center, prospective, randomized study in which 150 eyes of 117 patients were
      randomly divided into control (CT), TB, and BBG groups. Preoperative and
      postoperative (1, 3, and 6 months) values for corrected distance visual acuity
      (CDVA), corneal endothelial cell count, and central corneal thickness were
      compared among the three groups. RESULTS: A total of 111 eyes from 88 patients
      were completely analyzed. The CDVA (logarithm of the minimal angle of resolution)
      values in the CT, TB, and BBG groups 1 month after surgery were 0.001, 0.023, and
      0.019, respectively. The corneal endothelial cell counts 6 months after surgery
      were 2711 +/- 225, 2748 +/- 251, and 2680 +/- 284 cells/mm2, respectively. The
      central corneal thicknesses 6 months after surgery were 524.3 +/- 35.5, 532.2 +/-
      36.1, and 531.4 +/- 33.0 um, respectively. There were no significant differences
      in CDVA, endothelial cell count, or central corneal thickness among the three
      groups during the follow-up period. CONCLUSIONS: Our findings indicate that
      neither TB nor BBG was associated with detectable toxicity to corneal endothelial
      cells during cataract surgery, even when injected directly into the anterior
      chamber. Additionally, BBG exhibited equivalent staining efficiency to TB.

PMID- 29188472
TI  - Small Intestinal Bacterial Overgrowth: Should Screening Be Included in the Pre
      fecal Microbiota Transplantation Evaluation?
AB  - BACKGROUND: Fecal microbiota transplantation (FMT) is safe and effective for
      recurrent Clostridium difficile infection (rCDI) and often involves terminal
      ileal (TI) stool infusion. Patients report gastrointestinal (GI) symptoms post
      FMT despite rCDI resolution. Small intestinal bacterial overgrowth (SIBO)
      screening is not routinely performed pre-FMT. The effect of donor/recipient SIBO
      status on FMT outcomes and post-FMT GI symptoms is unclear. We aim to evaluate
      the value of pre-FMT SIBO screening on post-FMT outcomes and symptoms. METHODS:
      This was a prospective pilot study of consecutive adults with rCDI undergoing FMT
      by colonoscopy at a tertiary center. Routine pre-FMT screening and baseline
      lactulose breath tests (LBTs) were performed for donors and recipients. Positive
      LBT required a rise > 20 ppm in breath hydrogen or any methane level > 10 ppm
      within 90 min. The presence of GI symptoms and CDI resolution were assessed 8
      weeks post-FMT. Fisher's exact/Student's t tests were performed for statistical
      analyses. RESULTS: Twenty recipients (58.3 years, 85% women) enrolled in the
      study. Fourteen (70%) FMTs involved TI stool infusion. Four (20%) recipients and
      six (30%) donors had positive LBT pre-FMT. At 8 weeks post-FMT, 17 (85%)
      recipients had CDI resolution and five (25%) reported GI symptoms. Pre-FMT LBT
      result was not associated with post-FMT CDI resolution or GI symptoms. There was
      a trend toward increased GI symptoms among recipients receiving stool from LBT
      positive donors (50 vs 14.2%, p = 0.09). CONCLUSIONS: FMT is effective and well
      tolerated for rCDI. Positive LBT in asymptomatic donors may have an effect on
      post-FMT GI symptoms. Larger studies are needed.

PMID- 29188473
TI  - Effect of simvastatin on sensorial, motor, and morphological parameters in
      sciatic nerve crush induced-neuropathic pain in rats.
AB  - The present study compares the effects of a low and high doses of simvastatin in
      a model of peripheral neuropathy by evaluating sensorial, motor, and
      morphological parameters. First, male Wistar rats were orally treated with
      vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg,
      s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by
      crushing the sciatic nerve, and mechanical and cold allodynia, nerve function,
      histology, MPO and NAG concentrations, as well as mevalonate induced-nociception
      were evaluated. Animals were orally treated with vehicle, simvastatin, or
      gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the
      inflammatory pain induced by formalin, but failed to decrease the paw edema.
      Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day
      after injury and until the 18th day by gabapentin. However, both simvastatin and
      gabapentin treatments failed in attenuated cold allodynia or improved motor
      function. Interestingly, both doses of simvastatin showed a neuroprotective
      effect and inhibited MPO activity without altering kidney and hepatic parameters.
      Additionally, only the higher dose of simvastatin reduced the cholesterol levels
      and the nociception induced by mevalonate. Our results reinforce the
      antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin
      administration, which can strongly contribute to the sciatic nerve morphology
      preservation. Furthermore, our data suggest that lower and higher doses of
      simvastatin present beneficial effects that are dependent and independent of the
      mevalonate pathway, respectively, without causing signs of nerve damage.

PMID- 29188474
TI  - Temporal Anaphora with Spanish Imperfecto.
AB  - This paper argues against the assumption that Spanish-and more generally Romance
      imperfective past (IMP) is an intrinsically anaphoric tense. It is a widely
      accepted view that IMP requires a temporal discourse antecedent to be licensed.
      My aim is to show that such requirement is not actually in force when IMP
      combines with a stative/atelic predicate. In fact, with stative/atelic
      predicates, IMP (a) is acceptable in isolated sentences with no suitable
      antecedent available, (b) is able to access implicit assumptions that are not
      available with telic predicates-but do not behave as real antecedents, and (c)
      does not trigger certain perspectivisation effects that depend on the existence
      of a temporal antecedent. As a result, an asymmetry arises between continuous and
      habitual interpretations of IMP, which do not require retrieving a temporal
      antecedent, and progressive and narrative interpretations, which do need an
      accessible antecedent. Thus, the relevance of a discourse antecedent varies
      according to the lexical aspect of the predicate and the corresponding
      interpretations, and the alleged anaphoric nature of IMP cannot be a feature of
      its semantics: it is rather pragmatically derived from imperfectivity.

PMID- 29188476
TI  - Interpersonal Needs, Depressive Symptoms, and Suicide Ideation in a Sample of
      Portuguese Elderly Patients Recovering from Acute Medical Conditions.
AB  - The aim of the present study was to test whether perceived burdensomeness and
      thwarted belongingness are related to suicide ideation, when controlling for
      depressive symptoms. The sample consisted of elderly patients recovering from
      acute medical conditions who were recruited in a medical recovery clinic. Results
      demonstrated that depressive symptoms and thwarted belongingness related to the
      suicide ideation item of the Beck Depression Inventory-II, used as an indicator
      of suicide ideation. Depressive symptoms and thwarted belongingness also
      discriminated between participants with suicide ideation and participants without
      suicide ideation as defined by suicide items of the Symptom-Driven Diagnostic
      System for Primary Care. Results are discussed in terms of potential cultural
      influences, and clinical implications are highlighted.

PMID- 29188478
TI  - [Comprehensive geriatric care for frail elderly at home: a feasibility study].
AB  - OBJECTIVE: To evaluate the feasibility of a study on the content and effect of
      comprehensive geriatric care (CGC) at home for frail elderly. METHOD: Case
      managers invited new CGC patients of one care organization for participation in
      the study. At two moments, questionnaires were conducted on (social) functioning,
      quality of life, perceived problems, perceived informal caregiver burden, and
      self-management. Information on received care was collected from the patients'
      medical records, In addition, a questionnaire was administered to the referring
      physician. Feasibility was evaluated descriptively on three domains; inclusion,
      follow up, and data collection. RESULTS: The intended number of 25 participants
      was not reached, mostly because clients did not comply with inclusion criteria,
      and because case managers felt uncomfortable asking patients for participation in
      the study. Of the 14 participants, 12 were followed until the follow-up
      measurement. Several questionnaire domains appeared difficult to answer for
      participants. It also appeared difficult to collect information on received care
      from the medical records. Questionnaire response among general practitioners was
      6 out of 11. CONCLUSION: Due to the vulnerability of the targeted group and
      logistical challenges, the inclusion of participants for the study was more
      difficult than originally thought. In combination with the difficulties in data
      collection, this suggests that a large-scale study on the content and effect of
      CGC is not feasible. Qualitative research methodologies, preferably combined with
      quantitative methods, offer better opportunities to understand the value of CGC
      for frail elderly living at home.

PMID- 29188477
TI  - CRISPR/Cas9-mediated efficient editing in phytoene desaturase (PDS) demonstrates
      precise manipulation in banana cv. Rasthali genome.
AB  - The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated protein 9 (Cas9) has been reported for precise genome modification in
      many plants. In the current study, we demonstrate a successful mutation in
      phytoene desaturase (RAS-PDS) of banana cv. Rasthali using the CRISPR/Cas9
      system. Two PDS genes were isolated from Rasthali (RAS-PDS1 and RAS-PDS2), and
      their protein sequence analysis confirmed that both PDS comprises conserved
      motifs for enzyme activity. Phylogenetic analysis of RAS-PDS1 and RAS-PDS2
      revealed a close evolutionary relationship with other monocot species. The tissue
      specific expression profile of RAS-PDS1 and RAS-PDS2 in Rasthali suggested
      differential regulation of the genes. A single 19-bp guide RNA (gRNA) was
      designed to target the conserved region of these two RAS-PDS and transformed with
      Cas9 in embryogenic cell suspension (ECS) cultures of cv. Rasthali. Complete
      albino and variegated phenotype were observed among regenerated plantlets. DNA
      sequencing of 13 plants confirmed the indels with 59% mutation frequency in RAS
      PDS, suggesting activation of the non-homologous end-joining (NHEJ) pathway. The
      majority of mutations were either insertion (1-5) or deletion (1-4) of
      nucleotides near to protospacer adjacent motif (PAM). These mutations have
      created stop codons in RAS-PDS sequences which suggest premature termination of
      RAS-PDS protein synthesis. The decreased chlorophyll and total carotenoid
      contents were detected in mutant lines that revealed the functional disruption of
      both RAS-PDS genes. Our results demonstrate that genome editing through
      CRISPR/Cas9 can be applied as an efficient tool for banana genome modification.

PMID- 29188475
TI  - Current Perspectives on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are
      considered a delayed-type hypersensitivity reaction to drugs. They represent true
      medical emergencies and an early recognition and appropriate management is
      decisive for the survival. SJS/TEN manifest with an "influenza-like" prodromal
      phase (malaise, fever), followed by painful cutaneous and mucous membrane
      (ocular, oral, and genital) lesions, and other systemic symptoms. The difference
      between SJS, SJS/TEN overlap, and TEN is defined by the degree of skin
      detachment: SJS is defined as skin involvement of < 10%, TEN is defined as skin
      involvement of > 30%, and SJS/TEN overlap as 10-30% skin involvement. The
      diagnosis of different degrees of epidermal necrolysis is based on the clinical
      assessment in conjunction with the corresponding histopathology. The mortality
      rates for SJS and TEN have decreased in the last decades. Today, the severity-of
      illness score for toxic epidermal necrolysis (SCORTEN) is available for SJS/TEN
      severity assessment. Drugs with a high risk of causing SJS/TEN are anti-infective
      sulfonamides, anti-epileptic drugs, non-steroidal anti-inflammatory drugs of the
      oxicam type, allopurinol, nevirapine, and chlormezanone. Besides conventional
      drugs, herbal remedies and new biologicals should be considered as causative
      agents. The increased risk of hypersensitivity reactions to certain drugs may be
      linked to specific HLA antigens. Our understanding of the pathogenesis of SJS/TEN
      has improved: drug-specific T cell-mediated cytotoxicity, genetic linkage with
      HLA- and non-HLA-genes, TCR restriction, and cytotoxicity mechanisms were
      clarified. However, many factors contributing to epidermal necrolysis still have
      to be identified, especially in virus-induced and autoimmune forms of epidermal
      necrolysis not related to drugs. In SJS/TEN, the most common complications are
      ocular, cutaneous, or renal. Nasopharyngeal, esophageal, and genital mucosal
      involvement with blisters, erosions as well as secondary development of
      strictures also play a role. However, in the acute phase, septicemia is a leading
      cause of morbidity and fatality. Pulmonary and hepatic involvement is frequent.
      The acute management of SJS/TEN requires a multidisciplinary approach. Immediate
      withdrawal of potentially causative drugs is mandatory. Prompt referral to an
      appropriate medical center for specific supportive treatment is of utmost
      importance. The most frequently used treatments for SJS/TEN are systemic
      corticosteroids, immunoglobulins, and cyclosporine A.

PMID- 29188479
TI  - Racial disparity in breast cancer: can it be mattered for prognosis and therapy.
AB  - Breast cancer (BC) has emerged as a deadly disease that affects the lives of
      millions of women worldwide. It is the second leading cause of cancer-related
      deaths in the United States. Advancements in BC screening, preventive measures
      and treatment have resulted in significant decline in BC related deaths. However,
      unacceptable levels of racial disparity have been consistently reported,
      especially in African-American (AA) women compared to European American (EA). AA
      women go through worse prognosis, shorter survival time and higher mortality
      rates, despite higher cancer incidence reported in EA. These disparities are
      independent of socioeconomic status, access to healthcare or age, or even the
      stage of BC. Recent race-specific genetic and epigenetic studies have reported
      biological causes, which form the crux of this review. However, the developments
      are just the tip of the iceberg. Prioritizing primary research towards studying
      race-specific tumor microenvironment and biological composition of the host
      system in delineating the cause of these disparities is utmost necessary to
      ameliorate the disparity and design appropriate diagnosis/treatment regimen for
      AA women suffering from BC. In this review article, we discuss emerging trends
      and exciting discoveries that reveal how genetic/epigenetic circuitry contributed
      to racial disparity and discussed the strategies that may help in future
      therapeutic development.

PMID- 29188480
TI  - A function-blocking CD47 antibody modulates extracellular vesicle-mediated
      intercellular signaling between breast carcinoma cells and endothelial cells.
AB  - Tumor cells release extracellular vesicles (EVs) into the tumor microenvironment
      that may facilitate malignant progression and metastasis. Breast carcinoma EVs
      express high levels of the thrombospondin-1 and signal regulatory protein-alpha
      receptor CD47, which is the target of several experimental therapeutics currently
      in clinical trials. We analyzed changes in gene expression and function in human
      umbilical vein endothelial cells (HUVEC) induced by treatment with EVs derived
      from breast carcinoma cells and the effects of the function-blocking CD47
      antibody B6H12 on the resulting intercellular communication. CD47+ EVs exhibited
      greater uptake by HUVEC compared to CD47- EVs, but the CD47 antibody did not
      inhibit their uptake. Global and targeted analyses of transcripts demonstrated
      that treatment of HUVEC with EVs derived from MDA-MB-231 breast carcinomas cells
      altered pathways associated with tumor necrosis factor-alpha signaling,
      angiogenesis, lymphangiogenesis, endothelial-mesenchymal transition, and
      extracellular matrix. EVs from triple-negative MDA-MB-231 cells were more active
      than EVs from less metastatic breast carcinoma cell lines. Treatment with MDA-MB
      231 EVs down-regulated VEGFR2 mRNA expression and tyrosine phosphorylation while
      enhancing phosphorylation of the tyrosine phosphatase SHP2. VEGFR2 expression and
      phosphorylation in HUVEC was further inhibited by the CD47 antibody. Consistent
      with the observed changes in endothelial-mesenchymal transition genes and SHP2,
      treatment with MDA-MB-231-derived EVs decreased Zeb1 protein levels in HUVEC,
      whereas the CD47 antibody increased Zeb1 levels. The induction of E-selectin and
      other known targets of tumor necrosis factor-alpha signaling by EVs was also
      enhanced by the CD47 antibody, and E-selectin was the most up-regulated
      transcript following CD47 antibody treatment alone. These studies reveal several
      mechanisms by which therapeutics targeting CD47 could modulate tumor growth by
      altering the cross talk between cancer-derived EVs and nonmalignant cells in the
      tumor stroma.

PMID- 29188482
TI  - The association of alcohol use and quality of life in depressed and non-depressed
      individuals: a cross-sectional general population study.
AB  - PURPOSE: To compare the associations of alcohol-related variables with Quality of
      Life (QoL) in depressed and non-depressed individuals of the general population.
      METHODS: This cross-sectional study utilized data from the FINRISK 2007 general
      population survey. A subsample (n = 4020) was invited to participate in an
      interview concerning alcohol use. Of them, 2215 (1028 men, 1187 women; response
      rate 55.1%) were included in the analyses. Bivariate associations between mean
      weekly alcohol consumption, frequency of binge drinking, Alcohol Use Disorders
      Identification Test (AUDIT)-score and QoL were analysed according to
      categorization into depressed and non-depressed using the Beck Depression
      Inventory, Short Form. Linear regression models were calculated in order to
      determine the associations of the alcohol variables and QoL after adjusting for
      socio-demographic variables as well as somatic and mental illness. RESULTS:
      Depressed individuals had lower mean QoL and higher AUDIT-scores than non
      depressed respondents. Bivariate correlations showed that mean weekly alcohol
      consumption, frequency of binge drinking and AUDIT-scores were statistically
      significantly associated with impaired QoL in depressed individuals. Abstinence
      was not associated with QoL. After adjustment for covariates, frequency of binge
      drinking and AUDIT-score were statistically significantly associated with QoL in
      depressed individuals and AUDIT-score in the non-depressed group. When analysing
      all respondents regardless of depression, both AUDIT-score and binge drinking
      were associated with QoL. CONCLUSIONS: Of the alcohol-related variables, binge
      drinking and alcohol problems indicated by AUDIT-score contributed to impaired
      QoL in depressed individuals and both should be assessed as part of the clinical
      management of depression.

PMID- 29188481
TI  - Using case management in a universal health coverage system to improve quality of
      life of frequent Emergency Department users: a randomized controlled trial.
AB  - PURPOSE: Frequent Emergency Department users are likely to experience poor
      quality of life (QOL). Case management interventions are efficient in responding
      to the complex needs of this population, but their effects on QOL have not been
      tested yet. Therefore, the aim of our study was to examine to what extent a case
      management intervention improved frequent Emergency Department users' QOL in a
      universal health coverage system. METHODS: Data were part of a randomized
      controlled trial designed to improve frequent Emergency Department users' QOL at
      the Lausanne University Hospital, Switzerland. A total of 250 frequent Emergency
      Department users (>= 5 attendances during the previous 12 months) were randomly
      assigned to the control (n = 125) or the intervention group (n = 125). The latter
      benefited from case management intervention. QOL was evaluated using the WHOQOL
      BREF at baseline, two, five and a half, nine, and twelve months later. It
      included four dimensions: physical health, psychological health, social
      relationship, and environment. Linear mixed-effects models were used to analyze
      the change in the patients' QOL over time. RESULTS: Patients' QOL improved
      significantly (p < 0.001) in both groups for all dimensions after two months.
      However, environment QOL dimension improved significantly more in the
      intervention group after 12 months. CONCLUSIONS: Environment QOL dimension was
      the most responsive dimension for short-term interventions. This may have been
      due to case management's assistance in obtaining income entitlements, health
      insurance coverage, stable housing, or finding general health care practitioners.
      Case management in general should be developed to enhance frequent users' QOL.
      TRIAL REGISTRATION: http://www.clinicaltrials.gov , Unique identifier:
      NCT01934322.

PMID- 29188483
TI  - Minimal clinically important differences in the EORTC QLQ-C30 and brief pain
      inventory in patients undergoing re-irradiation for painful bone metastases.
AB  - PURPOSE: The EORTC QLQ-C30 and the Brief Pain Inventory (BPI) are validated tools
      for measuring quality of life (QOL) and the impact of pain in patients with
      advanced cancer. Interpretation of these instrument scores can be challenging and
      it is difficult to know what numerical changes translate to clinically
      significant impact in patients' lives. To address this issue, our study sought to
      establish the minimal clinically important differences (MCID) for these two
      instruments in a prospective cohort of patients with advanced cancer and painful
      bone metastases. METHODS: Both anchor-based and distribution-based methods were
      used to estimate the MCID scores from patients enrolled in a randomized phase III
      trial evaluating two different re-irradiation treatment schedules. For the anchor
      based method, the global QOL item from the QLQ-C30 was chosen as the anchor.
      Spearman correlation coefficients were calculated for all items and only those
      items with moderate or better correlation (|r| >= 0.30) with the anchor were used
      for subsequent analysis. A 10-point difference in the global QOL score was used
      to classify improvement and deterioration, and the MCID scores were calculated
      for each of these categories. These results were compared with scores obtained by
      the distribution-method, which estimates the MCID purely from the statistical
      characteristics of the sample population. RESULTS: A total of 375 patients were
      included in this study with documented pain responses and completed QOL
      questionnaires at 2 months. 9/14 items in the QLQ-C30 and 6/10 items in the BPI
      were found to have moderate or better correlation with the anchor. For
      deterioration, statistically significant MCID scores were found in all items of
      the QLQ-C30 and BPI. For improvement, statistically significant MCID scores were
      found in 7/9 items of the QLQ-C30 and 2/6 items of the BPI. The MCID scores for
      deterioration were uniformly higher than the MCIDs for improvement. Using the
      distribution-based method, there was good agreement between the 0.5 standard
      deviation (SD) values and anchor-based scores for deterioration. For improvement,
      there was less agreement and the anchor-based scores were lower than the 0.5 SD
      values obtained from the distribution-based method. CONCLUSION: We present MCID
      scores for the QLQ-C30 and BPI instruments obtained from a large cohort of
      patients with advanced cancer undergoing re-irradiation for painful bone
      metastases. The results from this study were compared to other similar studies
      which showed larger MCID scores for improvement compared to deterioration. We
      hypothesize that disease trajectory and patient expectations are important
      factors in understanding the contrasting results. The results of this study can
      guide clinicians and researchers in the interpretation of these instruments.

PMID- 29188484
TI  - An evaluation of the structural validity of the shoulder pain and disability
      index (SPADI) using the Rasch model.
AB  - PURPOSE: The shoulder pain and disability index (SPADI) has been extensively
      evaluated for its psychometric properties using classical test theory (CTT). The
      purpose of this study was to evaluate its structural validity using Rasch model
      analysis. METHODS: Responses to the SPADI from 1030 patients referred for
      physiotherapy with shoulder pain and enrolled in a prospective cohort study were
      available for Rasch model analysis. Overall fit, individual person and item fit,
      response format, dependence, unidimensionality, targeting, reliability and
      differential item functioning (DIF) were examined. RESULTS: The SPADI pain
      subscale initially demonstrated a misfit due to DIF by age and gender. After
      iterative analysis it showed good fit to the Rasch model with acceptable
      targeting and unidimensionality (overall fit Chi-square statistic 57.2, p = 0.1;
      mean item fit residual 0.19 (1.5) and mean person fit residual 0.44 (1.1); person
      separation index (PSI) of 0.83. The disability subscale however shows significant
      misfit due to uniform DIF even after iterative analyses were used to explore
      different solutions to the sources of misfit (overall fit (Chi-square statistic
      57.2, p = 0.1); mean item fit residual 0.54 (1.26) and mean person fit residual
      0.38 (1.0); PSI 0.84). CONCLUSIONS: Rasch Model analysis of the SPADI has
      identified some strengths and limitations not previously observed using CTT
      methods. The SPADI should be treated as two separate subscales. The SPADI is a
      widely used outcome measure in clinical practice and research; however, the
      scores derived from it must be interpreted with caution. The pain subscale fits
      the Rasch model expectations well. The disability subscale does not fit the Rasch
      model and its current format does not meet the criteria for true interval-level
      measurement required for use as a primary endpoint in clinical trials. Clinicians
      should therefore exercise caution when interpreting score changes on the
      disability subscale and attempt to compare their scores to age- and sex
      stratified data.

PMID- 29188486
TI  - Phase-field modelling of gravity-capillary waves on a miscible interface.
AB  - Using the approach of direct numerical simulations we investigate the gravity
      capillary waves induced on a horizontal interface between two slowly miscible
      liquids. It is assumed that the liquids are just brought into contact, and thus
      the interface is slowly smeared by the action of interfacial diffusion. It is
      also assumed that the initial shape of the interface is distorted by harmonic
      perturbations, which results in the development of the gravity-capillary surface
      waves. The evolution of the binary mixture is modelled on the basis of the phase
      field method. Our results show that in the limiting case of negligible diffusion
      the classical dispersion relations for immiscible interfaces can be reproduced.
      Although, for the waves with shorter wavelengths such an agreement is more
      difficult to obtain. The interfacial diffusion brings an additional dissipation
      to the fluid system, strongly damping the development of the shorter waves. We
      also show that the mixing (or the transition of a binary system to the state of
      thermodynamic equilibrium) is intensified by the presence of the surface waves,
      and this effect is more important when the liquids are slowly miscible, i.e. when
      the interfacial diffusion is weak.

PMID- 29188485
TI  - Prospective associations of social isolation and loneliness with poor sleep
      quality in older adults.
AB  - PURPOSE: There is evidence for negative associations between social isolation and
      loneliness and sleep quality in older adults. However, it is unclear to what
      extent these two factors independently affect sleep quality. This study examined
      the simultaneous associations of social isolation and loneliness with sleep
      quality in a longitudinal study of older adults. METHODS: Data were analyzed from
      the Social Environment and Biomarkers of Aging Study in Taiwan collected in 2000
      and 2006, involving a cohort of 639 participants (mean age = 66.14, SD 7.26).
      Poisson regression models were conducted to examine the association of social
      isolation and/or loneliness with sleep quality at follow-up after adjusting for
      multiple confounding variables. RESULTS: Univariate analysis showed that sleep
      quality was inversely associated with both social isolation and loneliness. After
      demographic, health, cognitive factors, and depressive symptoms were controlled
      in multivariable analysis, social isolation at the baseline still predicted poor
      sleep quality 6 years later (incident rate ratio, IRR 1.14; 95% CI 1.04-1.24; p <
      0.01), while the association between loneliness and sleep quality was no longer
      significant (IRR 1.08; 95% CI 0.94-1.23; p = 0.27). The results were unchanged
      when participants who had poor sleep quality at the baseline were excluded from
      the analysis. CONCLUSIONS: These findings confirm an adverse effect of social
      isolation on the sleep quality of older adults, but indicate that this effect is
      independent of loneliness. Social isolation and loneliness seem to have distinct
      pathways in affecting the sleep quality of older adults.

PMID- 29188487
TI  - Sodium Metabisulfite: Effects on Ionic Currents and Excitotoxicity.
AB  - How sodium metabisulfite (SMB; Na2S2O5), a popular food preservative and
      antioxidant, interacts with excitable membrane and induces excitotoxicity is
      incompletely understood. In this study, the patch-clamp technique was used to
      investigate and record the electrophysiological effect of SMB on electrically
      excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to
      pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western
      blotting, to analyze sodium channel expression on hippocampi after chronic SMB
      treatment. It was found that voltage-gated Na+ current (I Na) was stimulated, and
      current inactivation and deactivation were slowed in SMB-treated (30 MUM) HL-1
      cardiomyocytes. SMB-induced increases of I Na were attenuated in cells treated
      with ranolazine (10 MUM) or eugenol (30 MUM). The current-voltage relationship of
      I Na shifted to slightly more negative potentials in SMB-treated cells, the peak
      I Na with an EC50 value of 18 MUM increased, and the steady-state inactivation
      curve of I Na shifted to a more positive potential. However, the tail component
      of the rapidly activating delayed-rectifier K+ current (I Kr) was dose
      dependently inhibited. Cell-attached voltage-clamp recordings in SMB-treated
      cells showed that the frequency of action currents and prolonged action potential
      were higher. In SMB-treated NSC-34 neurons, the peak I Na was higher; however,
      neither the time to peak nor the inactivation time constant (I Na) changed.
      Pilocarpine-induced seizures were exacerbated, and acute neuronal damage and
      chronic mossy fiber sprouting increased in SMB-treated rats. Western blotting
      showed higher expression of the sodium channel in cells after chronic SMB
      treatment. We conclude that SMB contributes to the sodium channel-activating
      mechanism through which it alters cellular excitability and excitotoxicity in
      wide-spectrum excitable cells.

PMID- 29188488
TI  - Lipopolysaccharide-Induced Microglia Activation Promotes the Survival of Midbrain
      Dopaminergic Neurons In Vitro.
AB  - Microglia are the resident immune cells of the central nervous system (CNS) and
      respond to a variety of endogenous and exogenous stimuli in order to restore cell
      and tissue homeostasis. Lipopolysaccharide (LPS) is one of these exogenous
      stimuli, constitutes a major component of the outer membrane of Gram-negative
      bacteria, and binds to the microglial pattern recognition receptor Toll-like
      receptor 4 (TLR4). LPS-induced microglia activation is believed to promote
      neurodegeneration by release of neurotoxic factors such as interleukin-1beta,
      tumor necrosis factor alpha, or nitric oxide. In the present study, we
      investigated whether the physical presence of microglia is required to promote
      neurotoxicity and whether microglia-derived factors are essential. Interestingly,
      we observed that dopaminergic (mDA) neuron survival was only affected in mixed
      neuron-glia cultures containing microglia but not in neuron-enriched cultures.
      Moreover, we clearly demonstrate that microglia-conditioned medium (MCM) after
      LPS treatment increased mDA neuron survival, process numbers as well as process
      length. The observed protective effects of MCM was rather caused by microglia
      derived factors and only partially dependent on the increase in reactive
      astrocytes. These results indicate that LPS-induced microglia activation does not
      necessarily have detrimental effects on mDA neurons and further support the
      hypothesis that activated microglia support neuron survival by release of
      neurotrophic and neuroprotective factors.

PMID- 29188489
TI  - Does the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 improve
      accuracy in reporting anterior lesions on multiparametric magnetic resonance
      imaging (mpMRI)?
AB  - INTRODUCTION: Multiparametric MRI (mpMRI) is useful in detecting anterior
      prostate tumours. Due to the location of anterior tumours, they are often
      diagnosed with a large size and may be suspicious for extra-prostatic extension
      (EPE). We aim to evaluate whether PI-RADS v2 is more accurate in assessing
      anterior prostate lesions identified on mpMRI compared to PI-RADS v1. METHODS:
      Patients with anterior prostate lesions diagnosed on mpMRI who proceeded to a
      cognitive fusion transperineal prostate biopsy were identified. Each mpMRI was
      blinded and read by two experienced prostate MRI radiologists and assigned a PI
      RADS v1 and PI-RADS v2 score, and the presence of EPE was estimated. Correlation
      was made with transperineal histopathology and, where relevant, radical
      prostatectomy histopathology. Concordance measures between PI-RADS v1 and PI-RADS
      v2, and between examiners of the same PI-RADS score were calculated using a
      weighted kappa. RESULTS: Fifty-eight consecutive men were identified. Concordance
      between the examiners for PI-RADS v1 and for v2 showed substantial agreement
      (version 1: weighted kappa 0.71; version 2: weighted kappa 0.69). There was no
      difference in accuracy when using PI-RADS v1 or PI-RADS v2 to predict clinically
      significant cancer. There was poor correlation between EPE measured on mpMRI
      compared with EPE in radical prostatectomy histopathology. CONCLUSION: PI-RADS v2
      is reproducible between radiologists but does not have improved accuracy for
      diagnosing anterior tumours of the prostate when compared to PI-RADS v1.
      Multiparametric MRI is accurate at detecting anterior tumours with a sensitivity
      of 86-88%.

PMID- 29188490
TI  - IgG4-Related Disease of the Appendix.

PMID- 29188491
TI  - Primary Colonic Lymphoma.
AB  - Primary colonic lymphoma is a rare large bowel malignancy usually found in the
      cecum or rectosigmoid junction. Because of its non-specific symptoms, patients
      often present with advanced disease requiring surgical intervention.
      Nevertheless, resection followed by chemotherapy appears to offer the best
      prognosis.

PMID- 29188492
TI  - Investigating the effects of subconcussion on functional connectivity using mass
      univariate and multivariate approaches.
AB  - There are concerns about the effects of subconcussive head impacts in sport, but
      the effects of subconcussion on brain connectivity are not well understood. We
      hypothesized that college football players experience changes in brain functional
      connectivity not found in athletes competing in lower impact sports or healthy
      controls. These changes may be spatially heterogeneous across participants,
      requiring analysis methods that go beyond mass-univariate approaches commonly
      used in functional MRI (fMRI). To test this hypothesis, we analyzed resting-state
      fMRI data from college football (n = 15), soccer (n = 12), and lacrosse players
      (n = 16), and controls (n = 29) collected at preseason and postseason time
      points. Regional homogeneity (ReHo) and degree centrality (DC) were calculated as
      measures of local and long-range functional connectivity, respectively. Standard
      voxel-wise analysis and paired support vector machine (SVM) classification
      studied subconcussion's effects on local and global functional connectivity.
      Voxel-wise analyses yielded minimal findings, but SVM classification had high
      accuracy for college football's ReHo (87%, p = 0.009) and no other group. The
      findings suggest subconcussion results in spatially heterogeneous changes in
      local functional connectivity that may only be detectible with multivariate
      analyses. To determine if voxel-wise and SVM analyses had similar spatial
      patterns, region-average t-statistic and SVM weight values were compared using a
      measure of ranking distance. T-statistic and SVM weight rankings exhibited
      significantly low ranking distance values for all groups and metrics,
      demonstrating that the analyses converged on a similar underlying effect.
      Overall, this research suggests that subconcussion in football may produce local
      functional connectivity changes similar to concussion.

PMID- 29188493
TI  - Lipid Droplet Fusion in Mammary Epithelial Cells is Regulated by
      Phosphatidylethanolamine Metabolism.
AB  - Mammary epithelial cells (MEC) secrete fat in the form of milk fat globules (MFG)
      which are found in milk in diverse sizes. MFG originate from intracellular lipid
      droplets, and the mechanism underlying their size regulation is still elusive.
      Two main mechanisms have been suggested to control lipid droplet size. The first
      is a well-documented pathway, which involves regulation of cellular triglyceride
      content. The second is the fusion pathway, which is less-documented, especially
      in mammalian cells, and its importance in the regulation of droplet size is still
      unclear. Using biochemical and molecular inhibitors, we provide evidence that in
      MEC, lipid droplet size is determined by fusion, independent of cellular
      triglyceride content. The extent of fusion is determined by the cell membrane's
      phospholipid composition. In particular, increasing phosphatidylethanolamine (PE)
      content enhances fusion between lipid droplets and hence increases lipid droplet
      size. We further identified the underlying biochemical mechanism that controls
      this content as the mitochondrial enzyme phosphatidylserine decarboxylase; siRNA
      knockdown of this enzyme reduced the number of large lipid droplets threefold.
      Further, inhibition of phosphatidylserine transfer to the mitochondria, where its
      conversion to PE occurs, diminished the large lipid droplet phenotype in these
      cells. These results reveal, for the first time to our knowledge in mammalian
      cells and specifically in mammary epithelium, the missing biochemical link
      between the metabolism of cellular complex lipids and lipid-droplet fusion, which
      ultimately defines lipid droplet size.

PMID- 29188494
TI  - Menin Modulates Mammary Epithelial Cell Numbers in Bovine Mammary Glands Through
      Cyclin D1.
AB  - Menin, the protein encoded by the MEN1 gene, is abundantly expressed in the
      epithelial cells of mammary glands. Here, we found MEN1/menin expression slowly
      decreased with advancing lactation but increased by the end of lactation. It
      happened that the number of bovine mammary epithelial cells decreases since
      lactation, suggesting a role of menin in the control of mammary epithelial cell
      growth. Indeed, reduction of menin expression through MEN1-specific siRNA
      transfection in the bovine mammary epithelial cells caused cell growth arrest in
      G1/S phase. Decreased mRNA and protein expression of Cyclin D1 was observed upon
      MEN1 knockdown. Furthermore, menin was confirmed to physically bind to the
      promoter region of Cyclin D1 through a ChIP assay, indicating that menin plays a
      regulatory role in mammary epithelial cell cycle progression. Moreover, lower
      expression of MEN1/menin induced increased epithelial cell apoptosis and caused
      extracellular matrix remodeling by down-regulating its associated genes, such as
      DSG2 and KRT5, suggesting that menin's role may also be involved in the control
      of cell-cell adhesion in normal mammary glands. Taken together, our data revealed
      an unknown molecular function of menin in epithelial cell proliferation, which
      may be important in the regulation of lactation behavior of mammary glands.

PMID- 29188495
TI  - Protein Biomarkers and Neuroproteomics Characterization of Microvesicles/Exosomes
      from Human Cerebrospinal Fluid Following Traumatic Brain Injury.
AB  - Recently, there have been emerging interests in the area of microvesicles and
      exosome (MV/E) released from brain cells in relation to neurodegenerative
      diseases. However, only limited studies focused on MV/E released post-traumatic
      brain injury (TBI) as they highlight on the mechanistic roles of released
      proteins. This study sought to examine if CSF samples from severe TBI patients
      contain MV/E with unique protein contents. First, nanoparticle tracking analysis
      determined MV/E from TBI have a mode of 74-98 nm in diameter, while control CSF
      MV/E have a mode of 99-104 nm. Also, there are more MV/E were isolated from TBI
      CSF (27.8-33.6 * 108/mL) than from control CSF (13.1-18.5 * 108/mL). Transmission
      electron microscopy (TEM) visualization also confirmed characteristic MV/E
      morphology. Using targeted immunoblotting approach, we observed the presence of
      several known TBI biomarkers such as alphaII-spectrin breakdown products (BDPs),
      GFAP, and its BDPs and UCH-L1 in higher concentrations in MV/E from TBI CSF than
      their counterparts from control CSF. Furthermore, we found presynaptic terminal
      protein synaptophysin and known exosome marker Alix enriched in MV/E from human
      TBI CSF. In parallel, we conducted nRPLC-tandem mass spectrometry-based proteomic
      analysis of two control and two TBI CSF samples. Ninety-one proteins were
      identified with high confidence in MV/E from control CSF, whereas 466 proteins
      were identified in the counterpart from TBI CSF. MV/E isolated from human CSF
      contain cytoskeletal proteins, neurite-outgrowth related proteins, and synaptic
      proteins, extracellular matrix proteins, and complement protein C1q subcomponent
      subunit B. Taken together, following severe TBI, the injured human brain released
      increased number of extracellular microvesicles/exosomes (MV/E) into CSF. These
      TBI MV/E contain several known TBI biomarkers and previously undescribed brain
      protein markers. It is also possible that such TBI-specific MV/E might contain
      cell to cell communication factors related to both cell death signaling a well as
      neurodegeneration pathways.

PMID- 29188496
TI  - The differential expression of novel circular RNAs in an acute lung injury rat
      model caused by smoke inhalation.
AB  - Acute lung injury caused by smoke inhalation is a common severe clinical
      syndrome. This study aimed to investigate the potential expression of circular
      RNAs during acute lung injury triggered by smoke inhalation. The acute lung
      injury rat model was established with smoke inhalation from a self-made smoke
      generator. The occurrence of acute lung injury was validated by an analysis of
      the bronchoalveolar lavage fluid and hematoxylin-eosin (HE) staining of lung
      tissues. Next-generation sequencing and quantitative PCR were performed to
      identify the differentially expressed circular RNAs associated with acute lung
      injury that was caused by smoke inhalation. The circular form of the identified
      RNAs was finally verified by multiple RT-PCR-based assays. The bronchoalveolar
      lavage fluid (BALF) and lung tissue analysis showed that smoke inhalation
      successfully induced acute injury in rats, as evidenced by the significantly
      altered cell numbers, including macrophages, neutrophils, and red blood cells,
      disrupted cell lining, and increased levels of interleukin-1beta, tumor necrosis
      factor-alpha, and IL-8 in lung tissues. Ten significantly differentially
      expressed circular RNAs were identified with next-generation sequencing and RT
      PCR. The circular form of these RNAs was verified by multiple RT-PCR-based
      assays. In conclusion, the identified circular RNAs were prevalently and
      differentially expressed in rat lungs after acute lung injury caused by smoke
      inhalation.

PMID- 29188497
TI  - Bexarotene, a Selective RXRalpha Agonist, Reverses Hypotension Associated with
      Inflammation and Tissue Injury in a Rat Model of Septic Shock.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that
      can activate or inhibit the expression of many target genes by forming a
      heterodimer complex with the retinoid X receptor (RXR). The aim of this study was
      to investigate effects of bexarotene, a selective RXRalpha agonist, on the
      changes in renal, cardiac, hepatic, and pulmonary expression/activity of
      inducible nitric oxide synthase (iNOS) and cytochrome P450 (CYP) 4F6 in relation
      to PPARalpha/beta/gamma-RXRalpha heterodimer formation in a rat model of septic
      shock. Rats were injected with dimethyl sulfoxide or bexarotene 1 h after
      administration of saline or lipopolysaccharide (LPS). Mean arterial pressure
      (MAP) and heart rate (HR) were recorded from rats, which had received either
      saline or LPS before and after 1, 2, 3, and 4 h. Serum iNOS, LTB4,
      myeloperoxidase (MPO), and lactate dehydrogenase (LDH) levels as well as tissue
      iNOS and CYP4F6 mRNA expression in addition to PPARalpha/beta/gamma and RXRalpha
      proteins were measured. LPS-induced decrease in MAP and increase in HR were
      associated with a decrease in PPARalpha/beta/gamma-RXRalpha heterodimer formation
      and CYP4F6 mRNA expression. LPS also caused an increase in systemic iNOS, LTB4,
      MPO, and LDH levels as well as iNOS mRNA expression. Bexarotene at 0.1 mg/kg
      (i.p.) prevented the LPS-induced changes, except tachycardia. The results suggest
      that increased formation of PPARalpha/beta/gamma-RXRalpha heterodimers and CYP4F6
      expression/activity in addition to decreased iNOS expression contributes to the
      beneficial effect of bexarotene to prevent the hypotension associated with
      inflammation and tissue injury during rat endotoxemia.

PMID- 29188498
TI  - Umbelliferone Alleviates Myocardial Ischemia: the Role of Inflammation and
      Apoptosis.
AB  - The present study was to investigate cardioprotective effects of umbelliferone
      (Umb) on coronary artery ligation-induced myocardial ischemia. The model of
      myocardial ischemia (MI) was induced by ligatured the left anterior descending
      coronary artery of SD rats. ST-segment elevation, lactate dehydrogenase (LDH),
      creatine kinase (CK), catalase (SOD), malondialdehyde (MDA), inflammatory
      cytokines, Toll-like receptors (TLRs)/nuclear factor (NF)-kappaBp65 pathway, and
      apoptosis were evaluated in rats treated with or without Umb. The results showed
      that Umb treatment could significantly decrease the elevation of the ST segment
      of electrocardiograph (ECG), the myocardial infarct size of MI significantly. The
      levels of LDH, CK, and MDA were suppressed, and the content of SOD was enhanced
      with Umb. The elevated concentration of inflammatory cytokines such as tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and IL-6 in MI
      rats was effectively reversed by the Umb administration. Also, TLR/NF-kappaB and
      apoptosis-related proteins in MI rats were restored respectively by Umb
      treatment. The protective effect of Umb against MI injury might be associated
      with inflammation and apoptosis pathway.

PMID- 29188499
TI  - What Is a Surgical Oncologist? : By the Editors of the Annals of Surgical
      Oncology.

PMID- 29188500
TI  - Metastasectomy for Tumor-Infiltrating Lymphocytes: An Emerging Operative
      Indication in Surgical Oncology.
AB  - Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) is an
      emerging immunotherapy for metastatic cancer. Surgeons play a central role in ACT
      treatments by performing resection of tumors from which TILs are isolated. It is
      important that surgeons have familiarity with this emerging treatment method
      because it is increasingly performed for an expanding variety of solid tumors at
      institutions around the world. This report offers a brief introduction to ACT for
      cancer, highlights historical milestones in its development, and provides patient
      selection and operative considerations for surgeons called upon to perform
      metastasectomy for the purpose of isolating TILs.

PMID- 29188501
TI  - Correlation Between Biomarker Candidate Proteins with the Effect of Neoadjuvant
      Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: While chemoradiation therapy (CRT) is one of the most useful
      treatments for esophageal squamous cell carcinoma (ESCC), it is important to
      predict response prior to treatment by using markers because some patients
      respond well and others do not. METHODS: Fifty-nine patients with ESCC were
      treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression
      of seven types of biomarker candidate proteins in biopsy specimens of untreated
      primary tumors was evaluated to determine whether it correlated with response and
      prognosis. RESULTS: The positive expression rates were 47% for p53, 83% for
      CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54%
      for Nrf2. In terms of histological response, tumor grade of the 59 patients was
      48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3
      as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-),
      and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors
      independently correlated with effective histological response. Their combined
      expression of two or three negative expressions had 100% effective response and
      was a significant prognostic factor. CONCLUSION: Our results suggest that two or
      three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of
      primary tumors were associated with a favorable response to CRT for ESCC.
      Assessment of tumor suppressor and DNA repair protein expressions in biopsy
      specimens may be useful for the potential utility of CRT therapy for patients
      with ESCC prior to treatment.

PMID- 29188502
TI  - Small Scale Production of Recombinant Adeno-Associated Viral Vectors for Gene
      Delivery to the Nervous System.
AB  - Adeno-associated viral vectors have numerous applications in neuroscience,
      including the study of gene function in health and disease, targeting of light
      sensitive proteins to anatomically distinct sets of neurons to manipulate
      neuronal activity (optogenetics), and the delivery of fluorescent protein to
      study anatomical connectivity in the brain. Moreover several phase I/II clinical
      trials for gene therapy of eye and brain diseases with adeno-associated viral
      vectors have shown that these vectors are well tolerated by human patients. In
      this chapter we describe a detailed protocol for the small scale production of
      recombinant adeno-associated viral vectors. This protocol can be executed by
      investigators with experience in cell culture and molecular biological techniques
      in any well-equipped molecular neurobiology laboratory. With this protocol we
      typically obtain research batches of 100-200 MUL that range in titer from 5 *
      1012 to 2 * 1013 genomic copies/mL.

PMID- 29188503
TI  - Small and Micro-Scale Recombinant Adeno-Associated Virus Production and
      Purification for Ocular Gene Therapy Applications.
AB  - Over the past two decades recombinant adeno-associated virus (rAAV) vectors have
      emerged as the gold standard for transferring genetic material to cells of the
      retina. The ability to effectively produce small batches of rAAV vector at high
      enough purity for in vitro and in vivo applications in a cost-effective manner is
      paramount. This is particularly the case when conducting preclinical experiments
      to screen novel serotypes, promoters or transgenes, where production of numerous
      vector batches is required. Current vector production methods often produce large
      quantities of vector, limiting the cost-effectiveness and practicality of such
      screening experiments, which often require only small volumes of vector to carry
      out. Herein, we describe a method to produce high titer (1012-1013 vector genomes
      (vg)/mL) rAAV vector on small (~100 MUL) or micro (~15 MUL) scale for in vitro
      and in vivo applications.

PMID- 29188504
TI  - Design and Development of AAV-based Gene Supplementation Therapies for
      Achromatopsia and Retinitis Pigmentosa.
AB  - Achromatopsia (ACHM) and retinitis pigmentosa (RP) are inherited disorders caused
      by mutations in cone and rod photoreceptor-specific genes, respectively. ACHM
      strongly impairs daylight vision, whereas RP initially affects night vision and
      daylight vision at later stages. Currently, gene supplementation therapies
      utilizing recombinant adeno-associated virus (rAAV) vectors are being developed
      for various forms of ACHM and RP. In this chapter, we describe the procedure of
      designing and developing specific and efficient rAAV vectors for cone- and rod
      specific gene supplementation.

PMID- 29188505
TI  - Development of Multigenic Lentiviral Vectors for Cell-Specific Expression of
      Antiangiogenic miRNAs and Protein Factors.
AB  - Generation of lentivirus (LV)-based vectors holding multiple gene cassettes for
      coexpression of several therapeutic factors provides potent tools in both gene
      delivery studies as well as in gene therapy. Here we describe the development of
      such multigenic LV gene delivery vectors enabling cell-specific coexpression of
      antiangiogenic microRNA (miRNA) and protein factors and, if preferred, a
      fluorescent reporter, from RNApol(II)-driven expression cassettes orientated in a
      back-to-back fashion. This configuration may contribute to the development of new
      combination therapies for amelioration of diseases involving intraocular
      neovascularization including exudative age-related macular degeneration (AMD).

PMID- 29188506
TI  - Design and In Vitro Use of Antisense Oligonucleotides to Correct Pre-mRNA
      Splicing Defects in Inherited Retinal Dystrophies.
AB  - Antisense oligonucleotides (AONs) are small molecules able to bind to the pre
      mRNA and modulate splicing. The increasing amount of intronic mutations leading
      to pseudoexon insertion in genes underlying inherited retinal dystrophies (IRDs)
      has highlighted the potential of AONs as a therapeutic tool for these disorders.
      Here we describe how to design and test AON molecules in vitro in order to
      correct pre-mRNA splicing defects involved in IRDs.

PMID- 29188507
TI  - Three-Dimensional Co-Culture Bioassay for Screening of Retinal Gene Delivery
      Systems.
AB  - Herein we describe a three-dimensional co-culture bioassay protocol designed to
      assess the therapeutic potential of the proteins expressed from gene delivery
      transfected cells through the evaluation of expressed protein bioavailability and
      bioactivity. Using a combination of enzyme-linked immunosorbent assay (ELISA) and
      immunofluorescent-based neurite length profiling methodologies, the
      bioavailability of the secreted therapeutic protein in the medium can be
      quantitated, and the bioactivity of the secreted therapeutic protein can also be
      evaluated through neurite length profiling, respectively. The versatility and
      rationale of this bioassay could serve as a useful screening tool in the
      development of retinal gene delivery systems.

PMID- 29188508
TI  - Retinal Gene Therapy for Choroideremia: In Vitro Testing for Gene Augmentation
      Using an Adeno-Associated Viral (AAV) Vector.
AB  - As gene therapy of choroideremia is becoming a clinical reality, there is a need
      for reliable and sensitive assays to determine the expression of exogenously
      delivered Rab Escort Protein-1 (REP1), in particular to test new gene therapy
      vectors and as a quality control screen for clinical vector stocks. Here we
      describe an in vitro protocol to test transgene expression following AAV2/2-REP1
      transduction of a human cell line. Gene augmentation can be confirmed by western
      blot and quantification of the fold-increase of human REP1 levels over
      untransduced controls.

PMID- 29188509
TI  - In Vivo Electroporation of Developing Mouse Retina.
AB  - In vivo electroporation enables the transformation of retinal tissue with
      engineered DNA plasmids, facilitating the selective expression of desired gene
      products. This method achieves plasmid transfer via the application of an
      external electrical field, which both generates a transient increase in the
      permeability of cell plasma membranes, and promotes the incorporation of DNA
      plasmids by electrophoretic transfer through the permeabilized membranes. Here we
      describe a method for the preparation, injection, and electroporation of DNA
      plasmids into neonatal mouse retinal tissue. This method can be utilized to
      perform gain of function or loss of function studies in the mouse. Experimental
      design is limited only by construct availability.

PMID- 29188510
TI  - Methods for In Vivo CRISPR/Cas Editing of the Adult Murine Retina.
AB  - Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR
      associated protein (Cas) is used by some bacteria and most archaea to protect
      against viral phage intrusion and has recently been adapted to allow for
      efficient editing of the mammalian genome. Whilst CRISPR/Cas-based technology has
      been used to modify genes in mammalian cells in vitro, delivery of CRISPR/Cas
      system into mammalian tissue and/or organs is more difficult and often requires
      additional vectors. With the use of adeno-associated virus (AAV) gene delivery
      system, active CRISPR/Cas enzyme can be maintained for an extended period of time
      and enable efficient editing of genome in the retina in vivo. Herein we outline
      the method to edit the genome in mouse retina using a dual AAV vector -mediated
      CRISPR/Cas9 system.

PMID- 29188511
TI  - AAV Gene Augmentation Therapy for CRB1-Associated Retinitis Pigmentosa.
AB  - Mutations in the CRB1 gene account for around 10,000 persons with Leber
      congenital amaurosis (LCA) and 70,000 persons with retinitis pigmentosa (RP)
      worldwide. Therefore, the CRB1 gene is a key target in the fight against
      blindness. A proof-of-concept for an adeno-associated virus (AAV)-mediated CRB2
      gene augmentation therapy for CRB1-RP was recently described. Preclinical studies
      using animal models such as knockout or mutant mice are crucial to obtain such
      proof-of-concept. In this chapter we describe a technique to deliver AAV vectors,
      into the murine retinas, via the subretinal route. We also present protocols to
      detect expression of the therapeutic protein by fluorescence immunohistochemistry
      and to perform histological studies using ultra-thin sections stained with
      toluidine blue. These techniques in combination with electroretinography and
      visual behavior tests are in principle sufficient to obtain proof-of-concept for
      new gene therapies.

PMID- 29188512
TI  - Dual AAV Vectors for Stargardt Disease.
AB  - Stargardt disease (STGD1), due to mutations in the large ABCA4 gene, is the most
      common inherited macular degeneration in humans. Attempts at developing gene
      therapy approaches for treatment of STGD1 are currently ongoing. Among all the
      vectors available for gene therapy of inherited retinal diseases, those based on
      adeno-associated viruses (AAV) are the most promising given the efficacy shown in
      various animal models and their excellent safety profile in humans, as confirmed
      in many ongoing clinical trials. However, one of the main obstacles for the use
      of AAV is their limited effective packaging capacity of about 5 kb. Taking
      advantage of the AAV genome's ability to concatemerize , others and we have
      recently developed dual AAV vectors to overcome this limit. We tested dual AAV
      vectors for ABCA4 delivery, and found that they transduce efficiently both mouse
      and pig photoreceptors , and rescue the Abca4-/- mouse retinal phenotype,
      indicating their potential for gene therapy of STGD1. This chapter details how we
      designed dual AAV vectors for the delivery of the ABCA4 gene and describes the
      techniques that can be explored to evaluate dual AAV transduction efficiency in
      vitro and in the retina, and their efficacy in the mouse model of STGD1.

PMID- 29188513
TI  - Optogenetic Retinal Gene Therapy with the Light Gated GPCR Vertebrate Rhodopsin.
AB  - In retinal disease, despite the loss of light sensitivity as photoreceptors die,
      many retinal interneurons survive in a physiologically and metabolically
      functional state for long periods. This provides an opportunity for treatment by
      genetically adding a light sensitive function to these cells. Optogenetic
      therapies are in development, but, to date, they have suffered from low light
      sensitivity and narrow dynamic response range of microbial opsins. Expression of
      light-sensitive G protein coupled receptors (GPCRs), such as vertebrate rhodopsin
      , can increase sensitivity by signal amplification , as shown by several groups.
      Here, we describe the methods to (1) express light gated GPCRs in retinal
      neurons, (2) record light responses in retinal explants in vitro, (3) record
      cortical light responses in vivo, and (4) test visually guided behavior in
      treated mice.

PMID- 29188514
TI  - CRISPR Repair Reveals Causative Mutation in a Preclinical Model of Retinitis
      Pigmentosa: A Brief Methodology.
AB  - CRISPR/Cas9 genome engineering is currently the leading genome surgery technology
      in most genetics laboratories. Combined with other complementary techniques, it
      serves as a powerful tool for uncovering genotype-phenotype correlations. Here,
      we describe a simplified protocol that was used in our publication, CRISPR Repair
      Reveals Causative Mutation in a Preclinical Model of Retinitis Pigmentosa,
      providing an overview of each section of the experimental process.

PMID- 29188515
TI  - In-Depth Functional Analysis of Rodents by Full-Field Electroretinography.
AB  - Full-field electroretinography (ERG) belongs to the gold-standard of
      electrophysiological test systems in ophthalmology and reflects the sum response
      of the entire retina to light stimulation. The assessment of the retinal function
      is a fundamental diagnostic technique not only in the clinical ophthalmology it
      is also indispensable in the ophthalmic research, in particular, in therapeutic
      approaches where the in vivo follow up of the benefit after treatment is
      absolutely necessary. Several current therapeutic approaches have demonstrated
      long-lasting amelioration in respective disease models and show promise for a
      successful translation to human patients. In this chapter we provide
      electroretinography protocols of experimental data which may serve as informative
      features for upcoming gene therapeutic approaches and clinical trials.

PMID- 29188516
TI  - Advanced Ocular Injection Techniques for Therapy Approaches.
AB  - Treatment approaches for inherited eye diseases require local therapeutic
      molecule delivery by intraocular injection. One important factor that can
      influence the study outcome is the quality of intraocular administration. The
      intracompartmental structure (e.g., vitreous) of the eye allows a sustainable
      release of therapeutic biologicals using an intravitreal delivery. The protocol
      described here aims at providing the details relevant to perform a transscleral
      pars plana intravitreal transfer in small eyes using a genetically modified stem
      cell system. The fact that cells and therewith visually distinct particles are
      implanted, allows for the assessment of the implantation site and the
      distribution, and possibilities for temporal follow up studies-hence, valuable
      information becomes available which can be used to fine-tune the intravitreal
      delivery technique.

PMID- 29188517
TI  - Neutralizing Antibodies Against Adeno-Associated Virus (AAV): Measurement and
      Influence on Retinal Gene Delivery.
AB  - Adeno-associated viral vectors have become widely used in the clinic for retinal
      gene therapy. Thanks to AAVs impeccable safety profile and positive functional
      outcomes in its clinical application, interest in retinal gene therapy has
      increased exponentially over the past decade. Although early clinical trials have
      shown there is little influence of neutralizing antibodies on the performance of
      AAV when vector is administered into the subretinal space, recent findings
      suggest neutralizing antibodies may play a role when AAV is delivered via the
      intravitreal route. These findings highlight the importance of microenvironment
      on gene delivery and stress the need for a versatile assay to screen subjects for
      the presence of AAV-neutralizing antibodies. Measuring NAb titers against AAV
      prior and after gene therapy will help us better understand the impact of
      preexisting immunity on gene transfer, especially when the vector is administered
      intravitreally.

PMID- 29188519
TI  - Subretinal and Intravitreal Retinal Injections in Monkeys.
AB  - Ocular anatomy and physiology in cynomolgus monkeys (Macacca fascicularis) are
      very similar to that found in the human visual system. Therefore and despite
      significant ethical and economical implications, these animals constitute an
      excellent model system for toxicology and biodistribution studies in the
      development of new and meaningful treatment strategies for ocular disorders. The
      methods for delivery of investigational new drugs (INDs) to the ocular tissue are
      virtually identical to the methods used in clinical practice. This protocol
      explains in detail the method of applying INDs to the vitreous cavity or the
      subretinal space in monkeys.

PMID- 29188518
TI  - Screening for Neutralizing Antibodies Against Natural and Engineered AAV Capsids
      in Nonhuman Primate Retinas.
AB  - Adeno-associated virus (AAV) has shown promise as a therapeutic gene delivery
      vector for inherited retinal degenerations in both preclinical disease models and
      human clinical trials. The retinas of nonhuman primates (NHPs) share many
      anatomical similarities to humans and are an important model for evaluating AAV
      gene delivery. Recent evidence has shown that preexisting immunity in the form of
      neutralizing antibodies (NABs) in NHPs strongly correlates with weak or lack of
      AAV transduction in the retina when administered intravitreally, work with
      translational implications. This necessitates prescreening of NHPs before
      intravitreal delivery of AAV. In this chapter, we describe a method for screening
      NHP serum for preexisting NABs.

PMID- 29188520
TI  - Production of iPS-Derived Human Retinal Organoids for Use in Transgene Expression
      Assays.
AB  - In vitro retinal organoid modeling from human pluripotent stem cells is becoming
      more common place in many ophthalmic laboratories worldwide. These organoids
      mimic human retinogenesis through formation of organized layered retinal
      structures that display markers for typical retinal cell types. Pivotally these
      humanized retinal models provide a stepping stone to the clinic as therapeutic
      tools and are expected to provide a promising alternative to current animal
      models. Thus pluripotent stem cell based healthy as well as diseased human
      retinal organoids are attractive for use in drug potency assays and gene
      augmentation therapeutics. Here we outline an established protocol for generation
      of these retinal organoids and how they can be used in conjunction with adeno
      associated virus vectors for transgene expression assays.

PMID- 29188522
TI  - Human Retinal Explant Culture for Ex Vivo Validation of AAV Gene Therapy.
AB  - Recombinant adeno-associated viral (AAV) vectors have been successfully employed
      as the mode of gene delivery in several clinical trials for the treatment of
      inherited retinal diseases to date. The design of such vectors is critical in
      determining cellular tropism and level of subsequent gene expression that may be
      achieved following viral delivery. Here we describe a system for living retinal
      tissue extraction, ex vivo culture, viral transduction and assessment of
      transgene expression that may be used to assess viral constructs for gene therapy
      in the human retina at a preclinical stage.

PMID- 29188521
TI  - AAV Serotype Testing on Cultured Human Donor Retinal Explants.
AB  - This protocol details on a screening method for infectivity and tropism of
      different serotypes of adeno-associated viruses (AAVs) on human retinal explants
      with cell-type specific or ubiquitous green fluorescent protein (GFP) expression
      vectors. Eyes from deceased adult human donors are enucleated and the retinas are
      isolated. Each retina is punched into eight to ten 6-mm equal pieces. WhatmanTM
      paper punches are placed on the retinas and the stack is transferred onto 24-well
      culture inserts with the photoreceptors facing the membrane. AAVs are applied on
      the retinal explant punches to allow transduction for 48 h. Retinas are nourished
      by a serum-free Neurobasal(r)-A based medium composition that allows extended
      culturing of explants containing photoreceptor inner and outer segments. The
      protocols include quality control measurements and histological staining for
      retina cells. The cost and time effective procedure permits AAV transgene
      expression assays, RNAi knockdown, and pharmacological intervention on human
      retinas for 21 days ex vivo.

PMID- 29188524
TI  - Recording and Analysis of the Human Clinical Electroretinogram.
AB  - The electroretinogram (ERG) represents the biopotential that is produced by the
      retina in response to a light stimulus. To date, it remains the best diagnostic
      tool to objectively evaluate the functional integrity of the normal or diseased
      retina. In the following pages we briefly review the necessary requirements in
      order to record and analyze the conventional clinical ERG.

PMID- 29188523
TI  - Visual Acuity Testing Before and After Intravitreal Injection of rAAV2-ND4 in
      Patients.
AB  - Gene therapy in ophthalmology has developed rapidly, and there has been a
      breakthrough in the treatment of Leber's hereditary optic neuropathy. After
      receiving an intravitreal injection of rAAV2-ND4, patients followed up over a
      certain time period showed a definite increase in visual acuity. Visual acuity
      testing is critical for assessing the efficacy of rAAV2-ND4 intravitreal
      injection.

PMID- 29188525
TI  - Recording and Analysis of Goldmann Kinetic Visual Fields.
AB  - Goldmann kinetic perimetry is a commonly used method of evaluating the peripheral
      visual field. Ongoing gene therapy trials have targeted the central retina, but
      have nonetheless often included Goldmann kinetic perimetry as part of extensive
      preinterventional and postinterventional assessment. Future gene therapy trials
      may target the entire retina through intravitreal injections, as have drug
      therapeutic trials, further necessitating the evaluation of function across the
      entire retina. In the following pages, we will briefly review the necessary steps
      to perform and quantify the visual field, using the conventional Goldmann
      perimeter and the Field Digitizer software (version 4.20; Johns Hopkins
      Technology Ventures, Baltimore, USA), respectively.

PMID- 29188526
TI  - Measuring Central Retinal Sensitivity Using Microperimetry.
AB  - Microperimetry is an increasingly often used method of assessing the sensitivity
      of the central macula, analyzing fixation capabilities and loci, and accurately
      combining structural and functional information, even in the absence of stable
      fixation. Ongoing gene therapy trials have targeted the central retina, and
      utilized microperimetry as a main outcome measure for changes in retinal
      function. In retinal treatment planning, microperimetry has been used to assess
      the potential therapeutic window of opportunity. In the following pages, we
      briefly review the necessary steps to perform the Macular Integrity Assessment
      (MAIA) microperimetry.

PMID- 29188527
TI  - Inspection of the Human Retina by Optical Coherence Tomography.
AB  - Optical coherence tomography (OCT) is a high-resolution, three-dimensional,
      noninvasive imaging modality to examine the human retina. Since the introduction
      of spectral domain (SD-) OCT-the currently most used variant of OCT-previously
      unknown details of in vivo retinal morphology of a broad variety of pathologies
      have become visible. This chapter explains the basic principles of the OCT
      technology, deals with possible pitfalls in OCT examination or analysis, and
      hints at the use of OCT technology in functional imaging.

PMID- 29188528
TI  - Vector Shedding and Immunogenicity Sampling for Retinal Gene Therapy.
AB  - There has been recent growth in the number and magnitude of clinical trials for
      various forms of retinal gene therapy. Because of regulatory requirements, and to
      better understand vector safety profiles, there is a need for standardised and
      effective methods to collect, process, and store biological samples taken from
      trial patients that can be used to assess the dissemination of the vector within
      bodily fluids and any systemic cellular and humoral immune responses.

PMID- 29188529
TI  - Spinal ependymomas in NF2: a surgical disease?
AB  - The management of spinal cord ependymomas in Neurofibromatosis Type 2 (NF2) has
      traditionally been conservative, in contrast to the management of sporadic cases;
      the assumption being that, in the context of NF2, they did not cause morbidity.
      With modern management and improved outcome of other NF2 tumours, this
      assumption, and therefore the lack of role for surgery, has been questioned. To
      compare the outcome of conservative treatment of spinal ependymomas in NF2 with
      surgical intervention in selected patients. Retrospective review at two NF2
      centers, Manchester, UK and Paris/Lille, France. In Manchester patients were
      managed conservatively. In France surgery was a treatment option. Inclusion in
      the study was based on tumor length of greater than 1.5 cm. The primary parameter
      assessed was acquired neurological deficit measured by the Modified McCormick
      Outcome Score. 24 patients from Manchester and 46 patients from France were
      analyzed. From Manchester, 27% of these patients deteriorated during the course
      of follow-up. This effectively represents the natural history of ependymomas in
      NF2. Of the surgical cases, 23% deteriorated postoperatively, but only 2/18 (11%)
      of those operated on in the NF2 specialist centers. Comparison of the two
      specialist centers Manchester/France showed a significantly improved outcome (P =
      0.012, chi2 test) in the actively surgical center. Spinal ependymomas produce
      morbidity. Surgery can prevent or improve this in selected cases but can itself
      can produce morbidity. Surgery should be considered in growing/symptomatic
      ependymomas, particularly in the absence of overwhelming tumor load where
      bevacizumab is the preferred option.

PMID- 29188530
TI  - Histopathological vascular investigation of the peritumoral brain zone of
      glioblastomas.
AB  - To date, no histopathological vascular investigation focusing on peritumoral
      brain zone (PBZ) has been reported for glioblastoma. We analyzed 10 newly
      diagnosed cases of glioblastomas. For these PBZs, histopathological investigation
      was performed by hematoxylin-eosin (H&E) staining and immunohistochemistry was
      analyzed for CD31, CD34, Factor VIII, VEGF, VEGFR-1/2, Ki67, p53 and nestin.
      Although it was difficult to identify PBZ by H&E, Ki67 and p53 staining, there
      were apparent differences in nestin staining among PBZ, tumor core (TC), and
      normal zone (NZ). Therefore, in this study, we divided PBZ from TC and NZ by
      nestin staining. Differences in histological features, microvessel density,
      expression of VEGF and its receptors were assessed for PBZ, TC and NZ. The
      microvessel density, as determined by counting CD31, CD34 and VEGF receptors, and
      VEGF-A expression were lower in PBZ than TC. The expression patterns for CD31,
      CD34 and VEGF receptors in vessels show dissociation in PBZ. In addition, the
      vascular characteristics of the PBZ may correlate with findings of radiographic
      imaging. We provide the first clinicopathological evidence that PBZ exhibits
      unique angiogenic characteristics. These in situ observations will help to
      elucidate the mechanisms of tumor recurrence.

PMID- 29188531
TI  - MiR-519d-3p suppresses breast cancer cell growth and motility via targeting LIM
      domain kinase 1.
AB  - Breast cancer is the most common female cancer in women, and its estrogen
      receptor (ER)-negative subtype (ENBC) and triple-negative subtype (TNBC) have
      unfavorable prognosis in comparison with ER-positive subtype. MiRNAs are small
      noncoding RNAs that bind to the 3'-UTR region of targeting mRNAs to regulate gene
      expression. Mir-519d-3p was found to be associated with breast cancer for its
      potential role in proliferation and metastasis. To explore its potential role and
      mechanism of miR-519d-3p in breast carcinogenesis, we determined whether miR-519d
      3p regulates breast cancer cell proliferation and motility by performing wound
      healing assays and migration-invasion assays. We found that miR-519d-3p
      significantly inhibits proliferation and motility of ENBC and TNBC cells.
      Overexpression of miR-519d-3p arrested breast cancer cells in the G0/G1 phase and
      reduced the expression of CDK4, 6/Cyclin D1, and CDK2/Cyclin E1. It was reported
      that miR-519d-3p or miR-519d-3p expression was associated with cancer metastasis
      and clinical staging. Since LIM domain kinase 1 (LIMK1) was highly expressed in
      breast cancer and a major regulator of breast cancer growth and metastasis, we
      further demonstrated that LIMK1 is a potential target of miR-519d-3p by dual
      luciferase report assay. Mir-519d-3p decreases LIMK1 expression at mRNA and
      protein levels, and the protein level and phosphorylation of cofilin 1 (CFL1),
      one of the key downstream targets of LIMK1. Our findings suggest that miR-519d-3p
      regulates the LIMK1/CFL1 pathway in breast cancer and this new venue could be
      targeted for future breast cancer therapy.

PMID- 29188532
TI  - Lipopolysaccharide stimulates endogenous beta-glucuronidase via PKC/NF-kappaB/c
      myc signaling cascade: a possible factor in hepatolithiasis formation.
AB  - Hepatolithiasis is commonly encountered in Southeastern and Eastern Asian
      countries, but the pathogenesis mechanism of stone formation is still not well
      understood. Now, the role of endogenous beta-glucuronidase in pigment stones
      formation is being gradually recognized. In this study, the mechanism of
      increased expression and secretion of endogenous beta-glucuronidase during
      hepatolithiasis formation was investigated. We assessed the endogenous beta
      glucuronidase, c-myc, p-p65, and p-PKC expression in liver specimens with
      hepatolithiasis by immunohistochemical staining, and found that compared with
      that in normal liver samples, the expression of endogenous beta-glucuronidase, c
      myc, p-p65, and p-PKC in liver specimens with hepatolithiasis significantly
      increased, and their expressions were positively correlated with each other.
      Lipopolysaccharide (LPS) induced increased expression of endogenous beta
      glucuronidase and c-myc in hepatocytes and intrahepatic biliary epithelial cells
      in a dose- and time-dependent manner, and endogenous beta-glucuronidase secretion
      increased, correspondingly. C-myc siRNA transfection effectively inhibited the
      LPS-induced expression of endogenous beta-glucuronidase. Furthermore, NF-kappaB
      inhibitor pyrrolidine dithiocarbamate or PKC inhibitor chelerythrine could
      effectively inhibit the LPS-induced expression of c-myc and endogenous beta
      glucuronidase, and the expression of p-p65 was also partly inhibited by
      chelerythrine. Our clinical observations and experimental data indicate that LPS
      could induce the increased expression and secretion of endogenous beta
      glucuronidase via a signaling cascade of PKC/NF-kappaB/c-myc in hepatocytes and
      intrahepatic biliary epithelial cells, and endogenous beta-glucuronidase might
      play a possible role in the formation of hepatolithiasis.

PMID- 29188533
TI  - Effects of homocysteine and its related compounds on oxygen consumption of the
      rat heart tissue homogenate: the role of different gasotransmitters.
AB  - The objective of this study was to investigate in vitro effects of 10 uM DL
      homocysteine (DL-Hcy), DL-homocysteine thiolactone-hydrochloride (DL-Hcy TLHC),
      and L-homocysteine thiolactone-hydrochloride (L-Hcy TLHC) on the oxygen
      consumption of rat heart tissue homogenate, as well as the involvement of the
      gasotransmitters NO, H2S and CO in the effects of the most toxic homocysteine
      compound, DL-Hcy TLHC. The possible contribution of the gasotransmitters in these
      effects was estimated by using the appropriate inhibitors of their synthesis (N
      omega-nitro-L-arginine methyl ester (L-NAME), DL-propargylglycine (DL-PAG), and
      zinc protoporphyrin IX (ZnPPR IX), respectively). The oxygen consumption of rat
      heart tissue homogenate was measured by Clark/type oxygen electrode in the
      absence and presence of the investigated compounds. All three homocysteine-based
      compounds caused a similar decrease in the oxygen consumption rate compared to
      control: 15.19 +/- 4.01%, 12.42 +/- 1.01%, and 16.43 +/- 4.52% for DL-Hcy, DL-Hcy
      TLHC, or L-Hcy TLHC, respectively. All applied inhibitors of gasotransmitter
      synthesis also decreased the oxygen consumption rate of tissue homogenate related
      to control: 13.53 +/- 1.35% for L-NAME (30 uM), 5.32 +/- 1.23% for DL-PAG (10
      uM), and 5.56 +/- 1.39% for ZnPPR IX (10 uM). Simultaneous effect of L-NAME (30
      uM) or ZnPPR IX (10 uM) with DL-Hcy TLHC (10 uM) caused a larger decrease of
      oxygen consumption compared to each of the substances individually. However, when
      DL-PAG (10 uM) was applied together with DL-Hcy TLHC (10 uM), it attenuated the
      effect of DL-Hcy TLHC from 12.42 +/- 1.01 to 9.22 +/- 1.58%. In conclusion,
      cardiotoxicity induced by Hcy-related compounds, which was shown in our previous
      research, could result from the inhibition of the oxygen consumption, and might
      be mediated by the certain gasotransmitters.

PMID- 29188534
TI  - 1,25(OH)2-vitamin D3 upregulates glucose uptake mediated by SIRT1/IRS1/GLUT4
      signaling cascade in C2C12 myotubes.
AB  - This study examined the hypothesis that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)
      upregulates the insulin-independent signaling cascade of glucose metabolism.
      C2C12 myotubes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (0-50
      nM). 1,25(OH)2D3 supplementation upregulated both insulin-independent (SIRT1) and
      insulin-dependent (p-IRS) signaling molecules, and stimulated the GLUT4
      translocation, and glucose uptake in HG-treated myotubes. The effect of
      1,25(OH)2D3 on IRS1 phosphorylation, GLUT4 translocation, and glucose uptake was
      attenuated in SIRT1-knockdown myotubes. Treatment with 1,25(OH)2D3, coupled with
      insulin, enhanced GLUT4 translocation and glucose uptake compared to treatment
      with either insulin or 1,25(OH)2D3 alone in HG-treated myotubes, which suggests
      that insulin-independent signaling molecules can contribute to the higher glucose
      metabolism observed in 1,25(OH)2D3 and insulin-treated cells. The data,
      therefore, suggest that 1,25(OH)2D3 increases glucose consumption by inducing
      SIRT1 activation, which in turn increases IRS1 phosphorylation and GLUT4
      translocation in myotubes.

PMID- 29188535
TI  - Differential cellular responses by oncogenic levels of c-Myc expression in long
      term confluent retinal pigment epithelial cells.
AB  - c-Myc is a highly pleiotropic transcription factor known to control cell cycle
      progression, apoptosis, and cellular transformation. Normally, ectopic expression
      of c-Myc is associated with promoting cell proliferation or triggering cell death
      via activating p53. However, it is not clear how the levels of c-Myc lead to
      different cellular responses. Here, we generated a series of stable RPE cell
      clones expressing c-Myc at different levels, and found that consistent low level
      of c-Myc induced cellular senescence by activating AP4 in post-confluent RPE
      cells, while the cells underwent cell death at high level of c-Myc. In addition,
      high level of c-Myc could override the effect of AP4 on cellular senescence.
      Further knockdown of AP4 abrogated senescence-like phenotype in cells expressing
      low level of c-Myc, and accelerated cell death in cells with medium level of c
      Myc, indicating that AP4 was required for cellular senescence induced by low
      level of c-Myc.

PMID- 29188536
TI  - Inhibitory influence of natural flavonoids on human protein kinase CK2 isoforms:
      effect of the regulatory subunit.
AB  - CK2 is a pleiotropic, constitutively active protein kinase responsible for the
      phosphorylation of more than 300 physiological substrates. Typically, this enzyme
      is found in tetrameric form consisting of two regulatory subunits CK2beta and two
      catalytic subunits CK2alpha or CK2alpha'. Several natural occurring flavonoids
      were tested for their ability to inhibit both CK2 holoenzymes, CK2alpha2beta2 and
      CK2alpha'2beta2. We identified few substances selectively inhibiting only the
      alpha' subunit. Other compounds showed similar effect towards all four isoforms.
      In some cases, like chrysoeriol, pedalitin, apigenin, and luteolin, the
      alpha2beta2 holoenzyme was at least six times better inhibited than the free
      alpha subunit. Otherwise, we have found a luteolin derivative decreased the
      kinase activity of CK2alpha' with an IC50 value of 0.8 MUM, but the holoenzyme
      only with 9.5 uM.

PMID- 29188538
TI  - Analytical ultracentrifugation in structural biology.
AB  - Researchers in the field of structural biology, especially X-ray crystallography
      and protein nuclear magnetic resonance, are interested in knowing as much as
      possible about the state of their target protein in solution. Not only is this
      knowledge relevant to studies of biological function, it also facilitates
      determination of a protein structure using homogeneous monodisperse protein
      samples. A researcher faced with a new protein to study will have many questions
      even after that protein has been purified. Analytical ultracentrifugation (AUC)
      can provide all of this information readily from a small sample in a non
      destructive way, without the need for labeling, enabling structure determination
      experiments without any wasting time and material on uncharacterized samples. In
      this article, I use examples to illustrate how AUC can contribute to protein
      structural analysis. Integrating information from a variety of biophysical
      experimental methods, such as X-ray crystallography, small angle X-ray
      scattering, electrospray ionization-mass spectrometry, AUC allows a more complete
      understanding of the structure and function of biomacromolecules.

PMID- 29188539
TI  - Non-obstructive cardiovascular disease: a new challenge for invasive cardiology?

PMID- 29188537
TI  - Pretreatment with quercetin prevents changes in lymphocytes E-NTPDase/E-ADA
      activities and cytokines secretion in hyperlipidemic rats.
AB  - Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and
      inflammatory disorders. Purinergic system ectoenzymes play an important role in
      modulating the inflammatory and immune response. This study investigated whether
      the preventive treatment with quercetin is able to prevent changes caused by
      hyperlipidemia in the purinergic system, through the activities of E-NTPDase and
      E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the
      secretion of anti- and proinflammatory cytokines. Animals were divided into
      saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg,
      saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia,
      hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg,
      hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were
      pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced
      by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was
      administered after the induction of hyperlipidemia. Lymphocytes were isolated and
      E-NTPDase and E-ADA activities were determined. Serum was separated for the
      cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA
      activities were increased in lymphocytes from hyperlipidemic rats and
      pretreatment with quercetin was able to prevent the increase in the activities of
      these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving
      pretreatment with quercetin and treatment with simvastatin showed decreased
      levels of ATP and ADP when compared to the untreated hyperlipidemic group. The
      IFN-gamma and IL-4 cytokines were increased in the hyperlipidemic group when
      compared with control group, and decreased when hyperlipidemic rats received the
      pretreatment with quercetin. However, pretreatment with quercetin was able to
      prevent the alterations caused by hyperlipidemia probably by regulating the
      inflammatory process. We can suggest that the quercetin is a promising compound
      to be used as an adjuvant in the treatment of hyperlipidemia.

PMID- 29188540
TI  - Responses of two kidney bean (Phaseolus vulgaris) cultivars to the combined
      stress of sulfur deficiency and cadmium toxicity.
AB  - Plants suffer from combined stress of sulfur deficiency and cadmium toxicity in
      some agricultural lands. However, little is known about the reaction in plants,
      such as responses in antioxidant enzymes and non-protein thiol compounds, to such
      combined stress. Therefore, in this study, four treatments, S-sufficiency (TS
      Cd), S-deficiency (T-S-Cd), Cd stress (TS+Cd) and combined stress of S-deficiency
      and Cd stress (T-S+Cd), were set up to investigate (1) the effects of sulfur
      deficiency or sulfur sufficiency on Cd toxicity to kidney bean cultivar seedlings
      and the related mechanisms, and (2) the responses of two kidney bean cultivars to
      combined stress of S-deficiency and Cd-tolerance. The results showed significant
      increases in hydrogen peroxide (H2O2) and malondialdehyde contents and
      significant increases in antioxidant enzyme (superoxide dismutase, catalase,
      peroxidase, and glutathione S-transferase) activities and non-protein thiol
      compounds (non-protein thiols, reduced glutathione, phytochelatins) synthesis in
      the plants in TS+Cd and T-S+Cd. On the tissue level, higher proportion of Cd was
      found to be immobilized/deposited in roots, while on the sub-cell level, higher
      proportion of Cd was located in cell walls and vacuole fractions with lower in
      cell organelles. Taken together, the results indicated that Cd detoxification was
      achieved by the two kidney bean cultivars through antioxidant enzyme activation,
      non-protein thiol compound synthesis and sub-cellular compartmentalization. In
      addition, the results indicated that sufficient S supply helped to relieve Cd
      toxicity, which is of special significance for remediation or utilization of Cd
      contaminated soils as S is a plant essential nutrient.

PMID- 29188541
TI  - A Simple Approach for Synthesizing of Fluorescent Carbon Quantum Dots from Tofu
      Wastewater.
AB  - We present an investigation on carbon quantum dots (CQDs) synthesized from
      wastewater induced during the production of tofu. We find that tofu wastewater is
      a good source of raw material in making fluorescent CQDs. The corresponding CQDs
      can be fabricated simply via hydrothermal reaction to carbonize the organic
      matter in the yellow serofluid of tofu wastewater. Two sorts of CQDs can be
      obtained within the deionized water and NaOH solution, respectively, where the
      CQDs in water (NaOH solution) can emit blue (green) light under the UV
      irradiation. It is found from X-ray photoelectron spectroscopy (XPS) that the
      basic difference between these two sorts of CQDs is the contents of C-O and C=O
      bonds on the surface of the CQDs. This difference can cause different features of
      the photoluminescence (PL) spectra of the CQDs. On the basis of the obtained
      results from the XPS and PL measurements, we propose a mechanism in understanding
      and explaining the photon-induced light emission from CQDs. This study is
      relevant to the fabrication and application of fluorescent CQDs as, e.g., light
      display materials.

PMID- 29188542
TI  - Wet Beriberi Associated with Hikikomori Syndrome.
AB  - Wet beriberi, characterized by high cardiac output with predominantly right-sided
      heart failure and lactic acidosis, is a disease caused by thiamine deficiency,
      and is rarely seen in modern society. However, patients with social withdrawal
      syndrome, also known as hikikomori syndrome, may be a new population at risk of
      thiamine deficiency. Hikikomori syndrome, first recognized in Japan, is becoming
      a worldwide issue. A 39-year-old Japanese patient was brought to our hospital,
      with a 3-week history of progressive shortness of breath and generalized edema.
      The patient had right-sided high-output heart failure, lactic acidosis, and
      Wernicke-Korsakoff syndrome. Because of his history of social isolation, we
      diagnosed hikikomori syndrome according to the Japanese government's definition,
      which is as follows: lifestyle centered at home; no interest or willingness to
      attend school or work; persistence of symptoms beyond 6 months; and exclusion of
      other psychiatric and developmental disorders. Considering his diagnosis of
      hikikomori syndrome and social isolation, we suspected malnutrition, particularly
      thiamine deficiency, and successfully treated him. Clinicians should be aware of
      the potential risk of thiamine deficiency associated with hikikomori syndrome and
      initiate thiamine replacement in cases of high-output heart failure associated
      with lactic acidosis.

PMID- 29188543
TI  - Accelerating the Implementation of Social Determinants of Health Interventions in
      Internal Medicine.

PMID- 29188546
TI  - The Treachery Trope: Anti-Semitism as Indicative of a Psycho-Spiritual Disease
      Associated with the Betrayal of Cultural Ideals and of the Self.
AB  - The study seeks to place anti-semitism in a wider context by exploring the
      dynamics of betrayal-a designation often attributed to Jews, but also attributed
      to many victimized groups who are also deemed to be treacherous. The study argues
      that what lies at the heart of this practice is the betrayal (on the part of the
      victimizers) of ideological or personal principles that have not been realized.
      Instead of taking responsibility for this painful failure, those who have
      betrayed their principles project their treachery onto a set of victims who are
      accordingly punished as the 'true' embodiments of treachery. In view of this,
      cultural and personal health can only be improved if there is a greater
      consciousness of this psycho-spiritual dynamic; and, as the study suggests,
      principles associated with enlightenment may be brought to bear against this
      harmful affliction, which I have named the treachery rope.

PMID- 29188545
TI  - Historical Legacies, Social Capital, and Women's Decision-Making Power: Religion
      and Child Nutrition in Mozambique.
AB  - In sub-Saharan settings, parental religion may have important implications for
      children's health and well-being. Using survey data from rural Mozambique, we
      examine the relationship between women's religion and the likelihood of their
      children being chronically malnourished (stunted). Multivariate analyses show
      that children of religiously affiliated women are significantly less likely to be
      stunted than children of non-affiliated women. We also find a strong advantage of
      mainline Protestants, especially compared to members of Pentecostal-type
      denominations, net of other factors. We relate this advantage to two historically
      rooted characteristics of mainline Protestantism: its connections to the public
      health sector and higher levels of women's autonomy that it fosters.

PMID- 29188544
TI  - Keystrokes, Mouse Clicks, and Gazing at the Computer: How Physician Interaction
      with the EHR Affects Patient Participation.
AB  - BACKGROUND: Evidence is mixed regarding how physicians' use of the electronic
      health record (EHR) affects communication in medical encounters. OBJECTIVE: To
      investigate whether the different ways physicians interact with the computer
      (mouse clicks, key strokes, and gaze) vary in their effects on patient
      participation in the consultation, physicians' efforts to facilitate patient
      involvement, and silence. DESIGN: Cross-sectional, observational study of video
      and event recordings of primary care and specialty consultations. PARTICIPANTS:
      Thirty-two physicians and 217 patients. MAIN MEASURES: Predictor variables
      included measures of physician interaction with the EHR (mouse clicks, key
      strokes, gaze). Outcome measures included active patient participation (asking
      questions, stating preferences, expressing concerns), physician facilitation of
      patient involvement (partnership-building and supportive talk), and silence. KEY
      RESULTS: Patients were less active participants in consultations in which
      physicians engaged in more keyboard activity (b = -0.002, SE = 0.001, p = 0.02).
      More physician gaze at the computer was associated with more silence in the
      encounter (b = 0.21, SE = 0.09, p = 0.02). Physicians' facilitative
      communication, which predicted more active patient participation (b = 0.65, SE =
      0.14, p < 0.001), was not related to EHR activity measures. CONCLUSIONS: Patients
      may be more reluctant to actively participate in medical encounters when
      physicians are more physically engaged with the computer (e.g., keyboard
      activity) than when their behavior is less demonstrative (e.g., gazing at EHR).
      Using easy to deploy communication tactics (e.g., asking about a patient's
      thoughts and concerns, social conversation) while working on the computer can
      help physicians engage patients as well as maintain conversational flow.

PMID- 29188547
TI  - Humor as Wisdom for Reframing Life.
AB  - Human beings inevitably experience anxiety but attempt to avoid facing it through
      various forms of self-deception. This avoidance can lead to pathological
      symptoms. Young and middle-aged adults may be especially susceptible to suffering
      from anxiety because they are often single-mindedly pursuing means of achieving
      security. For these and others who fail to embrace life with warm enthusiasm,
      humor can serve to alleviate stress. This article views humor as a characteristic
      disposition of older adults-their humor signifying a sense of integrity and
      wisdom that often accompanies the aging process. Humor binds together feelings of
      despair and joy and contributes to a faithful reframing of faith and life. This
      article proposes that individuals acquire humor by perceiving the world as if on
      a journey to an exotic new place, seeing with new eyes even the most mundane of
      everyday objects and events. This capacity to perceive beauty in the ordinary
      world reflects a wisdom of older adults potentially available even to the young.

PMID- 29188548
TI  - Spiritist Hospital Chaplaincy in Brazil: 5 Years of Documented Experience.
AB  - Spiritist Hospital Chaplaincy in Brazil has been growing significantly in recent
      years, with the implementation of new services through the work of Spiritist
      Medical Associations (SMAs) in different regions of the country. This article
      describes the importance of historical interconnections from the advent of
      spiritism in the world and its introduction in Brazil to the emergence of
      Spiritist Hospital Chaplaincy in our country and presents the documented
      experience over 5 years of spiritist chaplain care, in the period from 2012 to
      2016, guided by the SMA of Piracicaba at the Unimed Hospital of Piracicaba (Sao
      Paulo). We documented 41,914 visits to 13,983 inpatients and an analysis of these
      records allowed us to reflect on the importance of this service and confirm its
      expansion and acceptance by different contemporary religious beliefs.

PMID- 29188549
TI  - Racial and Ethnic Differences in the Utilization of Prayer and Clergy Counseling
      by Infertile US Women Desiring Pregnancy.
AB  - Religion can have a significant influence on the experience of infertility.
      However, it is unclear how many US women turn to religion when facing
      infertility. Here, we examine the utilization of prayer and clergy counsel among
      a nationally representative sample of 1062 infertile US women. Prayer was used by
      74.8% of the participants, and clergy counsel was the most common formal support
      system utilized. Both prayer and clergy counsel were significantly more common
      among black and Hispanic women. Healthcare providers should acknowledge the
      spiritual needs of their infertile patients and ally with clergy when possible to
      provide maximally effective care.

PMID- 29188550
TI  - UDP-induced relaxation is enhanced in aorta from female obese Otsuka Long-Evans
      Tokushima Fatty rats.
AB  - Uridine 5'-diphosphate (UDP) plays an important role in controlling vascular
      tone; however, UDP-mediated response in metabolic syndromes, including obesity
      and type 2 diabetes in females, remains unclear. In this study, we investigated
      UDP-mediated response in the aorta of female obese Otsuka Long-Evans Tokushima
      Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. In OLETF
      rat aortas precontracted by phenylephrine (PE) (vs. LETO), (1) UDP-induced
      relaxation was increased, whereas acetylcholine (ACh)-induced relaxation was
      decreased; (2) no UDP- or ACh-induced relaxations were observed in endothelial
      denudation, whereas UDP-induced small contraction was observed; and (3) NG-nitro
      L-arginine [L-NNA, a nitric oxide (NO) synthase inhibitor] eliminated UDP-induced
      relaxation and small contraction, whereas caused contrasting responses by ACh,
      including slight relaxations (LETO) and contractions (OLETF). Indomethacin, a
      cyclooxygenase inhibitor, eliminated the difference in UDP- and ACh-induced
      relaxations between the groups by increased UDP-induced relaxation in the LETO
      group and increased ACh-induced relaxation in the OLETF group. MRS2578, a P2Y6
      receptor antagonist, eliminated the difference in UDP-induced relaxations between
      the groups by decreasing UDP-induced relaxation in the OLETF group. MRS2578 had
      no effect on UDP-induced contraction in endothelium-denuded aortas. Therefore,
      these findings demonstrate opposite trends of relaxations by UDP and ACh in OLETF
      and LETO rat aortas. These differences may be attributed to the imbalance between
      NO and vasoconstrictor prostanoids upon stimulations. Increased UDP-induced
      relaxation in OLETF rat aorta may be caused by the activation of endothelial
      MRS2578-sensitive P2Y6 receptor.

PMID- 29188551
TI  - Molecular Characterization of FMR1 Gene by TP-PCR in Women of Reproductive Age
      and Women with Premature Ovarian Insufficiency.
AB  - BACKGROUND: Fragile X syndrome is caused by CGG repeat expansion mutation in the
      FMR1 gene. Normal alleles have 5-44 CGG repeats with AGG interruptions. The
      expanded gray zone (GZ) (45-54 repeats) and premutation (PM) (55-200 repeats)
      alleles are often uninterrupted and are unstably inherited in subsequent
      generations. The prevalence of PM and GZ carriers is high in the female
      population, at 1/66 and 1/113, respectively, and PM is associated with fertility
      problems in 20% of cases. OBJECTIVE: Our objective was to molecularly
      characterize CGG repeats and AGG interruption sequences in the FMR1 gene in women
      of reproductive age and in women with premature ovarian insufficiency (POI).
      MATERIALS AND METHODS: We conducted molecular analysis of the FMR1 gene from 300
      women of reproductive age and 140 women with POI using triplet primed-polymerase
      chain reaction. This enabled us to identify carriers and to document CGG repeat
      size and the AGG interruption pattern. RESULTS: In women of reproductive age,
      1.7% were GZ carriers and 0.3% were PM carriers; in women with POI, 3.6% were GZ
      carriers and 2.14% were PM carriers. The frequency of GZ and PM carriers did not
      significantly differ between the cohorts (Fisher's exact test: p < 2.23 for GZ
      vs. control and p < 0.101 for PM vs. control). Carriers received genetic
      counselling; family screening identified an additional seven carriers.
      CONCLUSION: We documented preliminary data on the prevalence of GZ and PM
      carriers among the studied cohorts. The identification of PM carriers among women
      with POI serves a dual purpose of recognizing a cause for ovarian dysfunction and
      enabling genetic counselling, which will help carriers when making reproductive
      decisions.

PMID- 29188552
TI  - Intrahepatic subcapsular biloma after endoscopic retrograde
      cholangiopancreatography treated by endoscopic biliary drainage.
AB  - Several major complications from endoscopic retrograde cholangiopancreatography
      (ERCP), including pancreatitis, cholangitis, and hemorrhage have been discussed
      in detail; however, a few uncommon but severe complications have been reported.
      We encountered an unusual case of post-ERCP intrahepatic subcapsular biloma. An
      89-year-old woman with a 25-mm mass located at the hepatic hilum, suggestive of
      cholangiocarcinoma, underwent ERCP which demonstrated complete stricture of the
      common hepatic duct. Subsequently, two plastic stents were placed from the common
      bile duct to the right and left intrahepatic branches. On day 3, serum
      inflammatory markers were elevated and computed tomography revealed a large
      subcapsular fusiform fluid collection in the right liver, consistent with biloma.
      On day 6, the biloma ruptured and 500 ml of biliary ascites were removed. On day
      8, endoscopic nasobiliary drainage via the right intrahepatic branch was
      performed because of recurrence of biliary ascites. After the procedure, 150 ml
      of bile was collected through the drain every day and no ascites recurred. We
      believe that minor injury to the right intrahepatic bile duct due to guidewire
      manipulation caused the biloma. Biloma may become apparent several days after
      ERCP, and endoscopic biliary drainage placement adjacent to the bile duct rupture
      site can stop bile leakage.

PMID- 29188553
TI  - Sociodemographic Factors Mediate Race and Ethnicity-associated Childhood Asthma
      Health Disparities: a Longitudinal Analysis.
AB  - BACKGROUND: Race and ethnicity-based disparities in childhood asthma are well
      established. We characterized the longitudinal effects associated with being
      African-American/Black or Hispanic/Latino on a range of asthma outcomes, and the
      extent to which sociodemographic factors, caregiver health literacy, education
      level, and asthma knowledge mediate these associations. METHODS: Children ages 8
      15 and their caregivers (n = 544) in the Chicago Initiative to Raise Asthma
      Health Equity (CHIRAH) cohort completed interviews every 3 months for 1.5 years.
      Health literacy was measured with the Rapid Estimate of Adult Literacy in
      Medicine (REALM). Other covariates include sex, age, education level, income,
      smoke exposure, asthma duration, employment status, and insurance status. We
      conducted a series of models to evaluate these factors as mediators of the
      relationship between race/ethnicity and (1) asthma knowledge, (2) asthma-related
      quality of life, (3) asthma severity, and (4) asthma control based on NAEPP/EPR-3
      2007 guidelines. RESULTS: African-American race and Hispanic/Latino ethnicity
      were significantly associated with all outcomes when compared to Whites.
      Adjusting for sociodemographic factors resulted in the most significant mediation
      of racial/ethnic disparities in all outcomes. Health literacy was a partial
      mediator of race/ethnic disparities in asthma knowledge and asthma-related
      quality of life. Asthma knowledge remained significantly associated with race and
      ethnicity, and race remained associated with asthma-related quality of life.
      CONCLUSIONS: African-American race and Hispanic/Latino ethnicity are
      significantly associated with worse asthma compared to Whites in longitudinal
      analyses. Sociodemographic factors are potent mediators of these disparities, and
      should be considered when designing interventions to reduce asthma disparities.
      Health literacy and education level are partial mediators.

PMID- 29188555
TI  - Medical physics publishing in a changing research environment: the Australasian
      Physical & Engineering Sciences in Medicine 40th anniversary editorial.

PMID- 29188556
TI  - Current and Future Challenges in GPCR Drug Discovery.
AB  - GPCRs play a pervasive physiological role and, in turn, are the leading target
      class for pharmaceuticals. Beginning with the determination of the structure of
      rhodopsin, and dramatically accelerating since the reporting of the first ligand
      mediated GPCR X-ray structures, our understanding of the structural and
      functional characteristics of these proteins has grown dramatically. Deploying
      this now rapidly emerging information for drug discovery has already been
      extensively demonstrated through a watershed of studies appearing in numerous
      scientific reports. Included in these expositions are areas such as sites and
      characteristics of ligand to GPCR binding, protein activation, effector bias,
      allosteric mechanisms, dimerization, polypharmacology and others. Computational
      chemistry studies are demonstrating an increasing role in capitalizing on the
      structural studies to further advance our understanding of these proteins as well
      as to drive drug discovery. Such drug discovery activities range from the design
      of orthosteric site inhibitors through, for example, allosteric modulators,
      biased ligands, partial agonists and bitopic ligands. Herein, these topics are
      outlined through specific examples in the hopes of providing a glimpse of the
      state of the field.

PMID- 29188557
TI  - Characterization of Ligand Binding to GPCRs Through Computational Methods.
AB  - The recent increase in available G protein-coupled receptor structures now
      contributes decisively to the structure-based ligand design. In this context,
      computational approaches in combination with medicinal chemistry and pharmacology
      are extremely helpful. Here, we provide an update on our structure-based
      computational protocols, used to answer key questions related to GPCR-ligand
      binding. All combined, these techniques can shed light on ligand binding modes,
      determine the molecular basis of conformational selection, for agonists and
      antagonists, as well as of subtype selectivity. To illustrate each of these
      questions, we will consider examples from existing projects on three families of
      class A (rhodopsin-like) GPCRs: one small-molecule (nucleotide-like) family,
      i.e., the adenosine receptors, and two peptide-binding receptors: neuropeptide-Y
      and angiotensin II receptors. The successful application of the same
      computational protocols to investigate this diverse group of receptor families
      gives an idea of the general applicability of our methodology in the
      characterization of GPCR-ligand binding.

PMID- 29188559
TI  - A Structural Framework for GPCR Chemogenomics: What's In a Residue Number?
AB  - The recent surge of crystal structures of G protein-coupled receptors (GPCRs), as
      well as comprehensive collections of sequence, structural, ligand bioactivity,
      and mutation data, has enabled the development of integrated chemogenomics
      workflows for this important target family. This chapter will focus on cross
      family and cross-class studies of GPCRs that have pinpointed the need for, and
      the implementation of, a generic numbering scheme for referring to specific
      structural elements of GPCRs. Sequence- and structure-based numbering schemes for
      different receptor classes will be introduced and the remaining caveats will be
      discussed. The use of these numbering schemes has facilitated many chemogenomics
      studies such as consensus binding site definition, binding site comparison,
      ligand repurposing (e.g. for orphan receptors), sequence-based pharmacophore
      generation for homology modeling or virtual screening, and class-wide
      chemogenomics studies of GPCRs.

PMID- 29188558
TI  - Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug
      Design.
AB  - Recent crystallographic structures of G protein-coupled receptors (GPCRs) have
      greatly advanced our understanding of the recognition of their diverse agonist
      and antagonist ligands. We illustrate here how this applies to A2A adenosine
      receptors (ARs) and to P2Y1 and P2Y12 receptors (P2YRs) for ADP. These X-ray
      structures have impacted the medicinal chemistry aimed at discovering new ligands
      for these two receptor families, including receptors that have not yet been
      crystallized but are closely related to the known structures. In this Chapter, we
      discuss recent structure-based drug design projects that led to the discovery of:
      (a) novel A3AR agonists based on a highly rigidified (N)-methanocarba scaffold
      for the treatment of chronic neuropathic pain and other conditions, (b)
      fluorescent probes of the ARs and P2Y14R, as chemical tools for structural
      probing of these GPCRs and for improving assay capabilities, and (c) new more
      drug-like antagonists of the inflammation-related P2Y14R. We also describe the
      computationally enabled molecular recognition of positive (for A3AR) and negative
      (P2Y1R) allosteric modulators that in some cases are shown to be consistent with
      structure-activity relationship (SAR) data. Thus, computational modeling has
      become an essential tool for the design of purine receptor ligands.

PMID- 29188560
TI  - GPCR Homology Model Generation for Lead Optimization.
AB  - The vast increase of recently solved GPCR X-ray structures forms the basis for
      GPCR homology modeling to atomistic accuracy. Nowadays, homology models can be
      employed for GPCR-ligand optimization and have been reported as invaluable tools
      for drug design in the last few years. Elucidation of the complex GPCR
      pharmacology and the associated GPCR conformations made clear that different
      homology models have to be constructed for different activation states of the
      GPCRs. Therefore, templates have to be chosen accordingly to their sequence
      homology as well as to their activation state. The subsequent ligand placement is
      nontrivial, as some recent X-ray structures show very unusual ligand binding
      sites and solvent involvement, expanding the space of the putative ligand binding
      site from the generic retinal binding pocket to the whole receptor. In the
      present study, a workflow is presented starting from the selection of the target
      sequence, guiding through the GPCR modeling process, and finishing with ligand
      placement and pose validation.

PMID- 29188561
TI  - GPCRs: What Can We Learn from Molecular Dynamics Simulations?
AB  - Advances in the structural biology of G-protein Coupled Receptors have resulted
      in a significant step forward in our understanding of how this important class of
      drug targets function at the molecular level. However, it has also become
      apparent that they are very dynamic molecules, and moreover, that the underlying
      dynamics is crucial in shaping the response to different ligands. Molecular
      dynamics simulations can provide unique insight into the dynamic properties of
      GPCRs in a way that is complementary to many experimental approaches. In this
      chapter, we describe progress in three distinct areas that are particularly
      difficult to study with other techniques: atomic level investigation of the
      conformational changes that occur when moving between the various states that
      GPCRs can exist in, the pathways that ligands adopt during binding/unbinding
      events and finally, the influence of lipids on the conformational dynamics of
      GPCRs.

PMID- 29188562
TI  - Methods of Exploring Protein-Ligand Interactions to Guide Medicinal Chemistry
      Efforts.
AB  - We present a number of techniques to analyze protein-ligand interactions in the
      context of medicinal chemistry: crystal Contract Preferences, Electrostatic Maps
      and pharmacophore screening using Huckel Theory. Contact Preferences is a
      statistical technique to predict hydrophobic and hydrophilic geometry in receptor
      active sites. Electrostatic Maps use the Poisson-Boltzmann Equation to model
      solvation effects and are particularly useful for predicting hydrophobic regions.
      Pharmacophore annotation with Huckel Theory provides finer detail of hydrogen
      bonding interactions, including CH..O interactions. Applications to AblK:Gleevec
      and CDK2 virtual screening are presented.

PMID- 29188563
TI  - Exploring GPCR-Ligand Interactions with the Fragment Molecular Orbital (FMO)
      Method.
AB  - The understanding of binding interactions between any protein and a small
      molecule plays a key role in the rationalization of affinity and selectivity. It
      is essential for an efficient structure-based drug design (SBDD) process. FMO
      enables ab initio approaches to be applied to systems that conventional quantum
      mechanical (QM) methods would find challenging. The key advantage of the Fragment
      Molecular Orbital Method (FMO) is that it can reveal atomistic details about the
      individual contributions and chemical nature of each residue and water molecule
      toward ligand binding which would otherwise be difficult to detect without using
      QM methods. In this chapter, we demonstrate the typical use of FMO to analyze 19
      crystal structures of beta1 and beta2 adrenergic receptors with their
      corresponding agonists and antagonists.

PMID- 29188564
TI  - Molecular Basis of Ligand Dissociation from G Protein-Coupled Receptors and
      Predicting Residence Time.
AB  - G protein-coupled receptors (GPCRs) are integral membrane proteins and represent
      the largest class of drug targets. During the past decades progress in structural
      biology has enabled the crystallographic elucidation of the architecture of these
      important macromolecules. It also provided atomic-level visualization of ligand
      receptor interactions, dramatically boosting the impact of structure-based
      approaches in drug discovery. However, knowledge obtained through crystallography
      is limited to static structural information. Less information is available
      showing how a ligand associates with or dissociates from a given receptor, whose
      importance is in fact increasingly recognized by the drug research community.
      Owing to recent advances in computer power and algorithms, molecular dynamics
      stimulations have become feasible that help in analyzing the kinetics of the
      ligand binding process. Here, we review what is currently known about the
      dynamics of GPCRs in the context of ligand association and dissociation, as
      determined through both crystallography and computer simulations. We particularly
      focus on the molecular basis of ligand dissociation from GPCRs and provide case
      studies that predict ligand dissociation pathways and residence time.

PMID- 29188565
TI  - Methodologies for the Examination of Water in GPCRs.
AB  - The following chapter examines some of the current "state-of-the-art" tools for
      predicting, scoring, and examining explicit water molecules in proteins and
      protein/ligand complexes, highlighting some of the ways information can be
      readily examined in a manner that is useful in a drug discovery process.

PMID- 29188566
TI  - Methods for Virtual Screening of GPCR Targets: Approaches and Challenges.
AB  - Virtual screening (VS) has become an integral part of the drug discovery process
      and is a valuable tool for finding novel chemical starting points for GPCR
      targets. Ligand-based VS makes use of biochemical data for known, active
      compounds and has been applied successfully to many diverse GPCRs. Recent
      progress in GPCR X-ray crystallography has made it possible to incorporate
      detailed structural information into the VS process. This chapter outlines the
      latest VS techniques along with examples that highlight successful applications
      of these methods. Best practices for increasing the likelihood of VS success, as
      well as ongoing challenges, are also discussed.

PMID- 29188567
TI  - Approaches for Differentiation and Interconverting GPCR Agonists and Antagonists.
AB  - Predicting the functional preferences of the ligands was always a highly
      demanding task, much harder that predicting whether a ligand can bind to the
      receptor. This is because of significant similarities of agonists, antagonists
      and inverse agonists which are binding usually in the same binding site of the
      receptor and only small structural changes can push receptor toward a particular
      activation state. For G protein-coupled receptors, due to a large progress in
      crystallization techniques and also in receptor thermal stabilization, it was
      possible to obtain a large number of high-quality structures of complexes of
      these receptors with agonists and non-agonists. Additionally, the long-time-scale
      molecular dynamics simulations revealed how the activation processes of GPCRs can
      take place. Using both theoretical and experimental knowledge it was possible to
      employ many clever and sophisticated methods which can help to differentiate
      agonists and non-agonists, so one can interconvert them in search of the optimal
      drug.

PMID- 29188568
TI  - Opportunities and Challenges in the Discovery of Allosteric Modulators of GPCRs.
AB  - From the pharmacological point of view, allosteric modulators may present
      numerous advantages over orthosteric ligands. Growing availability of novel tools
      and experimental data provides a tempting opportunity to apply computational
      methods to improve known modulators and design novel ones. However, recent
      progress in understanding of complexity of allostery increases awareness of
      problems involved in design of modulators with desired properties. Deeper insight
      into phenomena such as probe dependence, altering signaling bias with minor
      changes in ligand structure, as well as influence of subtle endogenous allosteric
      factors turns out to be fundamental. These effects make the design of a modulator
      with precise pharmacological outcome a very challenging task, and need to be
      taken into consideration throughout the design process. In this chapter, we focus
      on nuances of targeting GPCR allosteric sites in computational drug design
      efforts, in particular with application of docking, virtual screening, and
      molecular dynamics.

PMID- 29188569
TI  - Challenges and Opportunities in Drug Discovery of Biased Ligands.
AB  - The observation of biased agonism in G protein-coupled receptors (GPCRs) has
      provided new approaches for the development of more efficacious and safer drugs.
      However, in order to rationally design biased drugs, one must understand the
      molecular basis of this phenomenon. Computational approaches can help in
      exploring the conformational universe of GPCRs and detecting conformational
      states with relevance for distinct functional outcomes. This information is
      extremely valuable for the development of new therapeutic agents that promote
      desired conformational receptor states and responses while avoiding the ones
      leading to undesired side-effects.This book chapter intends to introduce the
      reader to powerful computational approaches for sampling the conformational space
      of these receptors, focusing first on molecular dynamics and the analysis of the
      produced data through methods such as dimensionality reduction, Markov State
      Models and adaptive sampling. Then, we show how to seek for compounds that target
      distinct conformational states via docking and virtual screening. In addition, we
      describe how to detect receptor-ligand interactions that drive signaling bias and
      comment current challenges and opportunities of presented methods.

PMID- 29188570
TI  - Synergistic Use of GPCR Modeling and SDM Experiments to Understand Ligand
      Binding.
AB  - There is a substantial amount of historical ligand binding data available from
      site-directed mutagenesis (SDM) studies of many different GPCR subtypes. This
      information was generated prior to the wave of GPCR crystal structure, in an
      effort to understand ligand binding with a view to drug discovery. Concerted
      efforts to determine the atomic structure of GPCRs have proven extremely
      successful and there are now more than 80 GPCR crystal structure in the PDB
      database, many of which have been obtained in the presence of receptor ligands
      and associated G proteins. These structural data enable the generation of
      computational model structures for all GPCRs, including those for which crystal
      structures do not yet exist. The power of these models in designing novel
      ligands, especially those with improved residence times, and for better
      understanding receptor function can be enhanced tremendously by combining them
      synergistically with historic SDM ligand binding data. Here, we describe a
      protocol by which historic SDM binding data and receptor models may be used
      together to identify novel key residues for mutagenesis studies.

PMID- 29188571
TI  - Computational Support of Medicinal Chemistry in Industrial Settings.
AB  - The practice of computational chemistry in an industrial setting poses unique
      opportunities and challenges. Industrial computational chemists must manage large
      amounts of data, master modeling software, write scripts to perform custom
      calculations, and stay abreast of scientific advances in the field. Just as
      importantly, because computational chemists are full partners in the drug
      discovery effort at companies, in order to influence and streamline the drug
      discovery process, they must communicate effectively with medicinal chemists and
      other scientists to deliver results of their calculations in a timely fashion.
      The skills necessary to play this role require education that emphasizes a
      combination of chemistry, programming, and communication skills. Professors are
      encouraged to incorporate such training in their curriculum.

PMID- 29188573
TI  - Ligand-Based Methods in GPCR Computer-Aided Drug Design.
AB  - This chapter describes two powerful 3D ligand-based shape similarity and scoring
      methods called ROCS and EON, their basic operation and selected validation data.
      The steps required to prepare a database of molecules for successful use with
      ROCS and EON are described and selected examples of their application in
      prospective lead discovery experiments are summarized.

PMID- 29188572
TI  - Investigating Small-Molecule Ligand Binding to G Protein-Coupled Receptors with
      Biased or Unbiased Molecular Dynamics Simulations.
AB  - An increasing number of G protein-coupled receptor (GPCR) crystal structures
      provide important-albeit static-pictures of how small molecules or peptides
      interact with their receptors. These high-resolution structures represent a
      tremendous opportunity to apply molecular dynamics (MD) simulations to capture
      atomic-level dynamical information that is not easy to obtain experimentally.
      Understanding ligand binding and unbinding processes, as well as the related
      responses of the receptor, is crucial to the design of better drugs targeting
      GPCRs. Here, we discuss possible ways to study the dynamics involved in the
      binding of small molecules to GPCRs, using long timescale MD simulations or
      metadynamics-based approaches.

PMID- 29188574
TI  - Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of
      Structure-Based Drug Discovery.
AB  - GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead
      optimization (LO) stages of drug discovery. The aims of these modeling approaches
      are to predict the 3D structures of the receptor-ligand complexes, to explore the
      key interactions between the receptor and the ligand and to utilize these
      insights in the design of new molecules with improved binding, selectivity or
      other pharmacological properties. In this book chapter, we present a brief survey
      of key computational approaches integrated with hierarchical GPCR modeling
      protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of
      structure-based drug discovery (SBDD). We outline the differences in modeling
      strategies used in H2L and LO of SBDD and illustrate how these tools have been
      applied in three drug discovery projects.

PMID- 29188575
TI  - Cheminformatics in the Service of GPCR Drug Discovery.
AB  - Cheminformatics is a broad discipline covering a wide range of computational
      approaches, including the characterization of molecular similarity, pattern
      recognition, and predictive modeling. The unifying theme that these apparently
      disparate methods have in common is the aim of extracting useable information
      from the increasing amounts of data that are associated with contemporary drug
      discovery projects. Both proprietary and publically available data can be
      exploited to help inform and improve the process of developing novel therapeutic
      molecules targeting the GPCR family of proteins.

PMID- 29188576
TI  - Modeling and Deorphanization of Orphan GPCRs.
AB  - Despite tremendous efforts, approximately 120 GPCRs remain orphan. Their
      physiological functions and their potential roles in diseases are poorly
      understood. Orphan GPCRs are extremely important because they may provide novel
      therapeutic targets for unmet medical needs. As a complement to experimental
      approaches, molecular modeling and virtual screening are efficient techniques to
      discover synthetic surrogate ligands which can help to elucidate the role of
      oGPCRs. Constitutively activated mutants and recently published active structures
      of GPCRs provide stimulating opportunities for building active molecular models
      for oGPCRs and identifying activators using virtual screening of compound
      libraries. We describe the molecular modeling and virtual screening process we
      have applied in the discovery of surrogate ligands, and provide examples for
      CCKA, a simulated oGPCR, and for two oGPCRs, GPR52 and GPR34.

PMID- 29188577
TI  - Benefits of resistance training in physically frail elderly: a systematic review.
AB  - AIM: Exercise is one of the most important components in frailty prevention and
      treatment. Therefore, we systematically reviewed the effect of resistance
      training (RT) alone or combined with multimodal exercise intervention on muscle
      hypertrophy, maximal strength, power output, functional performance, and falls
      incidence in physically frail elderly. METHODS: MEDLINE, Cochrane CENTRAL, PEDro,
      and SPORTDiscus databases were searched from 2005 to 2017. Studies must have
      mentioned the effects of RT (i.e., included or not in multimodal training) on at
      least one of the following parameters: muscle mass, muscle strength, muscle
      power, functional capacity, and risk of falls in frail elderly. RESULTS: The
      initial search identified 371 studies and 16 were used for qualitative analysis
      for describing the effect of strength training performed alone or in a multimodal
      exercise intervention. We observed that RT alone or in a multimodal training may
      induce increases of 6.6-37% in maximal strength; 3.4-7.5% in muscle mass, 8.2% in
      muscle power, 4.7-58.1% in functional capacity and risk of falls, although some
      studies did not show enhancements. CONCLUSION: Frequency of 1-6 sessions per
      week, training volume of 1-3 sets of 6-15 repetitions and intensity of 30-70%1-RM
      promoted significant enhancements on muscle strength, muscle power, and
      functional outcomes. Therefore, in agreement with previous studies, we suggest
      that supervised and controlled RT represents an effective intervention in frailty
      treatment.

PMID- 29188578
TI  - Trajectory and variability characterization of the Montreal cognitive assessment
      in older adults.
AB  - BACKGROUND: The Montreal cognitive assessment (MoCA) has become one of the most
      widely used cognitive screening instruments since its initial publication. To
      date, only a handful of studies have explored longitudinal characteristics of the
      MoCA. AIM: The aim of this study is to characterize the trajectory of MoCA
      performance across a broad age continuum of older adults. METHODS: Data from 467
      cognitively normal participants were used in this analysis. The sample was
      grouped into four strata based on the participants' age at baseline (60-69, 70
      79, 80-89, and 90-99). Mixed model repeated measures (MMRM) analysis and mixed
      effects spline models were used to characterize the trajectory of MoCA scores in
      each age stratum and in the entire sample. Intrasubject standard deviation (ISD)
      was used to characterize the natural variability of individual MoCA performance
      over time. RESULTS: The ISD values for each of the age strata indicated that year
      to-year individual variation on the MoCA ranged from zero to three points. MMRM
      analysis showed that the 60-69 stratum remained relatively stable over time while
      the 70-79 and 80-89 strata both showed notable decline relative to baseline
      performance. The mixed-effects spline model showed that MoCA performance declines
      linearly across the older adult age span. DISCUSSION: Among cognitively normal
      older adults MoCA performance remains relatively stable over time, however across
      the older adult age-span MoCA performance declines in a linear fashion. These
      results will help clinicians better understand the normal course of MoCA change
      in older adults while researchers may use these results to inform sample size
      estimates for intervention studies. CONCLUSION: This study provides an enhanced
      view of the MoCA's intraindividual trajectory in normal elderly aged 60 and
      older.

PMID- 29188579
TI  - Sauna bathing, health, and quality of life among octogenarian men: the Helsinki
      Businessmen Study.
AB  - BACKGROUND AND AIM: Sauna-type bathing has increased worldwide, and it has been
      related to both harmful and beneficial effects. There are few studies of bathing
      in sauna in very old age. METHODS: The series consists of 524 mostly home-living
      survivors of the Helsinki Businessmen Study (HBS, mean age 86 years, range 80
      95), who in 2015 responded to a questionnaire survey about lifestyle (including
      sauna bathing), prevalent diseases, and health-related quality of life (HRQoL,
      RAND-36). RESULTS: Of the men 57.6% (n = 302) reported all-year round and 17.6%
      (n = 92) part-year sauna bathing. Sauna was currently used mostly once a week,
      but 10% bathed more than twice a week. Median time in the hot room was 15 min at
      80  degrees C. Among 45.7% of the men, the habit had decreased with ageing, and
      130 (24.8%) did not attend sauna. However, 92.2% of the latter had discontinued
      an earlier habit, respective proportions 20.7% and 75.0% among all-year and part
      year users. Overall, reasons for decreased sauna bathing were nonspecific or
      related to mobility problems or diverse health reasons (n = 63). The most
      frequent motivations for sauna were relaxation and hygienic reasons. Of the RAND
      36 domains physical function, vitality, social functioning, and general health
      were significantly better among sauna users than non-users. These differences
      partly remained after adjusting for prevalent diseases and mobility-disability.
      CONCLUSIONS: Regular sauna bathing was common among octogenarian men and was
      associated with better HRQoL. However, reverse causality must be taken into
      account in this cross-sectional study. The bathing habit seemed to be prudent and
      had decreased in almost half of the cohort.

PMID- 29188580
TI  - 10-year complete remission in a Philadelphia chromosome-positive acute
      lymphoblastic leukemia patient using imatinib without high-intensity chemotherapy
      or allogeneic stem cell transplantation.
AB  - The outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph
      ALL) has improved with the use of tyrosine kinase inhibitors, such as imatinib
      and dasatinib. We report a 63-year-old woman with Ph-ALL who maintained complete
      remission for 10 years using imatinib without high-intensity chemotherapy or
      allogeneic stem cell transplantation. She underwent induction therapy with
      imatinib plus prednisolone and achieved complete remission by day 53. Imatinib
      was continued until 103 months, when it was stopped in response to renal
      dysfunction; however, the patient continued to exhibit molecular remission at 120
      months. This is the first report in the literature describing a patient with Ph
      ALL who achieved remission for more than 10 years after treatment only with
      imatinib.

PMID- 29188581
TI  - Marked erythroblastosis in myelodysplastic syndrome induced by gastric
      hemorrhaging.

PMID- 29188582
TI  - A low birth weight infant with no malformations delivered by a primary immune
      thrombocytopenia patient treated with eltrombopag.
AB  - Primary immune thrombocytopenia (ITP) is defined by a low platelet count
      secondary to antibody-mediated platelet destruction or reductions in platelet
      production. Although eltrombopag is a thrombopoietin receptor agonist that
      increases platelet production in refractory or relapsed ITP, the influence on
      pregnancy is limited. We present the case of a pregnant 25-year-old ITP patient
      referred to our hospital with a history of two induced abortions. After
      eradication of Helicobacter pylori and with oral prednisolone at 8 mg/day,
      platelet count remained below 10,000/ul. Because she declined splenectomy,
      eltrombopag was initiated at 12.5 mg/day. Afterward, platelet count was
      maintained at over 50,000/ul. Twenty-one months later, pregnancy became apparent.
      She continued treatment, and cesarean section was performed at 37 weeks of
      gestation after administration of intravenous immunoglobulin, platelet
      transfusions, and steroids. The baby weighed only 1670 g but showed no
      malformations, and platelet count at birth was 416,000/ul. Studies of eltrombopag
      in pregnancy have not been reported. A case with administration of eltrombopag
      from the last trimester of pregnancy that resulted in low birth weight has been
      reported. Embryo lethality and reduced fetal weights have been reported from
      animal experiments. Further investigation about the relationship between low
      birth weight deliveries and eltrombopag is necessary.

PMID- 29188583
TI  - Infusions of Epstein-Barr virus-specific cytotoxic T lymphocytes as post
      remission therapy in high-risk post-transplant lymphoproliferative disorder
      patients: report of two cases.
AB  - Conventional therapeutic approaches to post-transplant lymphoproliferative
      disorder (PTLD) occurring after solid-organ transplantation have shown only
      limited success in achieving durable response. Key factors driving the
      pathogenesis of PTLD include Epstein-Barr virus (EBV) reactivation and impaired
      immune surveillance due to prolonged immune suppression. Thus, EBV-specific
      cytotoxic T lymphocytes (EBV-CTLs) have emerged as an alternative therapeutic
      approach for the treatment of EBV-associated PTLD by enhancing EBV-specific
      immunity. We evaluated the safety and efficacy of EBV latent membrane proteins
      (LMP)-1- and 2-specific CTLs in two PTLD patients at high risk for relapse.
      Following diagnosis, patients were initially treated with a combination of
      chemotherapy and/or radiotherapy. Patients then received a total of eight doses
      of 2 * 107 EBV-CTLs/m2. Following initial therapy, both patients achieved
      complete remission confirmed by FDG-PET/CT imaging. Post-remission therapy using
      adoptive transfer of EBV-CTLs was safe without immediate or late toxicities.
      Infusion of EBV-CTLs led to an overall reduction in plasma EBV levels in the
      peripheral blood, which was associated with long-term remission of both patients
      during a follow-up of more than 65 months. Further prospective studies with
      larger number of patients will be needed to confirm the role of EBV-CTLs as post
      remission therapy in high-risk PTLD.

PMID- 29188584
TI  - Enhancing the Validity of a Quality of Life Measure for Autistic People.
AB  - Accurate measurement of quality of life (QoL) is important for evaluation of
      autism services and trials of interventions. We undertook psychometric validation
      of the World Health Organisation measure-WHOQoL-BREF, examined construct validity
      of the WHO Disabilities module and developed nine additional autism-specific
      items (ASQoL) from extensive consultation with the autism community. The sample
      of 309 autistic people was recruited from the Adult Autism Spectrum Cohort-UK.
      The WHOQoL-BREF had good psychometric properties, including criterion,
      convergent, divergent and discriminant validity. The WHO Disabilities module
      showed adequate construct validity and reliability. The ASQoL items form a
      unitary factor of QoL, with one global item. Future studies can use the WHO
      measures alongside the ASQoL items to measure QoL of autistic people.

PMID- 29188585
TI  - Brief Report: How Accurate is Teacher Report of Autism Symptoms Compared to
      Parent Report?
AB  - The Checklist for Autism Spectrum Disorder (CASD) completed by a psychologist
      (following standardized procedures integrating parent interview data, teacher
      report, and clinical observations) was compared with the CASD completed
      independently by mothers and teachers in 168 children with ASD and 40 with ADHD
      (1-12 years). The 30 CASD autism symptoms are scored as present or absent. Using
      mother scores 36% of children with ASD scored below the autism diagnostic cutoff,
      and 75% scored below the cutoff based on teacher scores. Many symptoms deemed
      present by the psychologist were not reported on the mother and teacher CASD.
      Mother-teacher correlations indicated little correspondence. Mother and teacher
      CASD scores should never be used alone. Diagnostic instruments must be
      administered following standardized procedures.

PMID- 29188586
TI  - In Search of Culturally Appropriate Autism Interventions: Perspectives of Latino
      Caregivers.
AB  - Most evidence-based autism spectrum disorder (ASD) interventions are tested with
      primarily White, mid-upper class, English-speaking populations, despite the
      increase in Latino children with ASD in early intervention programs throughout
      the United States. Unfortunately, interventions that are incongruent with a
      target population's culture may be relatively ineffective. This mixed-methods
      study explored how culturally appropriate, feasible, and acceptable Latino
      caregivers perceived intervention models, strategies, and targets. Survey data
      were compared for 28 Latino and 27 non-Latino White parents of young children
      with ASD. Further, 20 Latino caregivers participated in focus groups to describe
      their challenges, perspectives and preferences for intervention strategies and
      models, and unmet needs from providers. These findings underscore the need for
      culturally modified interventions for Latino children and families.

PMID- 29188587
TI  - Focus on the Social Aspect of Autism.
AB  - Autism spectrum disorder (ASD) describes a set of neurodevelopmental disorders.
      Despite extensive ASD research lasting more than 60 years, its causes are still
      unknown. Without indicating the etiology, its development cannot be stopped. Over
      the years, both the definition and diagnostic criteria have developed. The number
      of ASD incidence is rising. The economical aspect should also be highlighted.
      This disorder presents particular challenges to affected children, their parents
      and physicians. The research of ASD, physician activities, policy making and
      raising the level of awareness must be coordinated. Special attention should be
      paid to the problem among adults with ASD.

PMID- 29188588
TI  - Sibling Relationships: Parent-Child Agreement and Contributions of Siblings With
      and Without ASD.
AB  - Research on the experiences of siblings of individuals with ASD and the quality
      of their sibling relationships has yielded mixed results. The present study
      examined the significance of parent- versus child-report of both positive and
      negative behaviors exhibited by siblings and their brothers and sisters with ASD
      within sibling dyads. Findings indicated that siblings were more positive in
      their assessment of the sibling relationship than were their parents. Siblings
      exhibited more positive behaviors within the sibling relationship than did their
      brothers and sisters with ASD, and were recipients of aggression. These findings
      are consistent with prior research suggesting that siblings tend to take on a
      caretaking role, and point to important targets for intervention.

PMID- 29188589
TI  - Psychometric Properties of Spanish Adaptation of the PDD-MRS Scale in Adults with
      Intellectual Developmental Disorders: The EVTEA-DI Scale.
AB  - Strategies for the early detection of autism spectrum disorders (ASD) in people
      with intellectual developmental disorder (IDD) are urgently needed, but few
      specific tools have been developed. The present study examines the psychometric
      properties of the EVTEA-DI, a Spanish adaptation of the PDD-MRS, in a large
      randomized sample of 979 adults with IDD. Factorial solution analysis suggested a
      three-factor solution (stereotyped behavior, communication, and social behavior).
      The EVTEA-DI showed good reliability and convergent validity when compared to the
      Childhood Autism Rating Scale. Discriminative validity analysis resulted in an
      acceptable global sensitivity of 70% and a high specificity of 90%. The EVTEA-DI
      proved to be a valid screening tool in ASD assessment of the adult Spanish
      population with IDD.

PMID- 29188590
TI  - Characteristics of Cobalt-Related Cardiomyopathy in Metal Hip Implant Patients:
      An Evaluation of 15 Published Reports.
AB  - Over 300,000 hip replacements occurred in the USA in 2010, and the frequency is
      likely increasing annually. Blood Cobalt (Co) concentrations in patients with
      well-functioning cobalt-chromium (Co-Cr) hip implants are usually elevated above
      background concentrations relative to the general population. Excessive Co
      exposure, in rare cases, can result in cardiomyopathy. The purpose of this review
      was to identify cases of cardiomyopathy in metal-containing hip implant patients
      and to evaluate the possible cause of each patient's cardiomyopathy. We evaluated
      15 cases published between 2009 and 2016, and, based on a review of the
      preexisting risk factors, blood Co concentrations, and histopathological
      information published for each patient, they were stratified into one of four
      categories regarding the association between Co exposure and the development of
      cardiomyopathy: (1) Co was causal (five cases); (2) Co was contributory (two
      cases); (3) Co was possibly contributory (six cases); and (4) Co was non-causal
      (two cases). In all 15 cases, blood Co concentrations (14-6521 MUg/L) were
      elevated beyond levels associated with the majority of metal-containing implant
      patients (0.1-10 MUg/L), and, in many cases, there was evidence of a
      malfunctioning implant. The data indicate that individuals with well-functioning
      implants, even those with preexisting risk factors, are at no risk of developing
      cardiac effects. We conclude that blood Co measurements are informative, but
      should be interpreted with caution, and in context of other factors evaluated in
      this analysis. The mere presence of elevated Co is not sufficient to indicate
      causation for a patient's cardiomyopathy.

PMID- 29188591
TI  - Contact Dermatitis after Prescription of an Ophthalmic Ointment Containing
      Fradiomycin Sulfate: A Retrospective Database Study Using Japanese Health
      Insurance Claims Data.
AB  - BACKGROUND: Topical ointments containing fradiomycin sulfate, such as fradiomycin
      sulfate/methylprednisolone (F/M) and fradiomycin sulfate/betamethasone sodium
      phosphate (F/B), are known to cause allergic contact dermatitis (CD) in some
      patients, especially when used for the periocular region. F/M is commonly
      prescribed to patients for various conditions; however, there are no reports with
      respect to the incidence of CD caused by F/M in actual practice. OBJECTIVE: The
      aim was to investigate the incidence of CD using a data-based retrospective
      cohort study. METHODS: Using a Japanese health insurance claims database
      [MinaCare Co. Ltd. healthcare database (MinaCare HDB)], a comparative assessment
      was conducted of F/M and another combination drug (F/B) and two single-drug
      treatments (ophthalmic ointments with either an antibiotic or a steroid). The
      total data set consisted of 1,176,082 individuals in the MinaCare HDB, with
      54,016 having received prescriptions for one of the four investigational drug
      regimens. RESULTS: Overall, the incidences of CD were similar in three of the
      four groups in this study (F/M 0.091; F/B 0.092; steroids 0.102), while being
      lower in the fourth group (antibiotics 0.060). Even after confirmation of a
      diagnosis of CD, prescriptions for the investigational drugs were repeatedly
      filled for some patients. CONCLUSION: This study demonstrated that there was no
      clear difference in the incidence of CD after filling prescriptions for F/M, F/B,
      and ophthalmic ointment containing a steroid, while the incidence with
      antibiotics was lower by 0.03-0.04 compared with the other groups. Considering
      the observation that the investigational drugs were repeatedly prescribed even
      after the diagnosis of CD, it is critical that the risk of CD with these
      prescribed topical ointments is better understood by primary care physicians in
      order to take appropriate countermeasures.

PMID- 29188593
TI  - Recreational physical activity and survival in African-American women with
      ovarian cancer.
AB  - PURPOSE: While recreational physical activity (RPA) has been associated with
      reduced mortality in breast, colorectal, and prostate cancers, evidence for
      epithelial ovarian cancer (EOC) is limited. Most EOC studies have been in
      predominantly white populations, although inactivity is more prevalent and
      survival is poorer among African-American (AA) women. We examined RPA before and
      after EOC diagnosis and associations with survival among AA women. METHODS: We
      analyzed data from 264 EOC survivors enrolled in a population-based, case-control
      study who completed surveys that included questions about pre- and post-diagnosis
      RPA. Data were collected on RPA frequency, intensity, and duration before
      diagnosis and approximately 1 year after the baseline interview. We calculated
      metabolic equivalent of task (MET)-hours/week for pre- and post-diagnosis RPA,
      and evaluated associations with risk of mortality using Cox proportional hazards
      models. RESULTS: RPA before diagnosis was not associated with mortality. Hazard
      ratios (HRs) for post-diagnosis RPA were < 1.0 but not statistically significant
      after adjustment for covariates; HRs were 0.94 (95% CI 0.58, 1.54) for > 0-9 MET
      hours/week and 0.53 (95% CI 0.21, 1.35) for > 9 MET-hours/week. CONCLUSIONS: Our
      results suggest that RPA may be inversely associated with mortality among AA
      women with ovarian cancer, although it is possible that the present study was
      underpowered to detect an association. There is a clear need for more studies of
      RPA after diagnosis in EOC survivors with attention to potential differences by
      race.

PMID- 29188594
TI  - Correction to: Community reporting of ambient air polychlorinated biphenyl
      concentrations near a Superfund site.
AB  - The original version of this article unfortunately contains a mistake. The
      correct Author names should be Staci M. Rubin and Keri C. Hornbuckle.

PMID- 29188595
TI  - Ethanol traces in natural waters checked using a new DMFC enzymatic device.
AB  - The use of fuels with strong percentage of ethanol that is done in countries such
      as Brazil and Australia causes a more and more relevant presence of traces of
      ethanol in natural waters. The ethanol present in these fuels seems to contribute
      to increase, through various mechanisms, the concentration of hydrocarbons in the
      same waters and soil. The ethanol content in natural waters must therefore be
      monitored frequently. It was therefore proposed a very simple innovative method,
      based on a catalytic fuel cell with the alcohol dehydrogenase enzyme immobilized
      in the anodic compartment of the device. The analytical performances of this new
      device were then evaluated by checking traces of alcohol in different types of
      natural waters (rain, river, and groundwater), with a good degree of precision
      and with an acceptable level of accuracy.

PMID- 29188596
TI  - Observed differentials in the levels of selected environmental contaminants among
      Mexican and other Hispanic American children, adolescents, adults, and senior
      citizens.
AB  - Starting with the 2007-2008 cycle, the National Health and Nutrition Examination
      Survey (NHANES) also oversampled Hispanics other than Mexicans (OHISP) making it
      possible to treat OHISP as a separate demographic group along with Mexican
      Americans (MAs), non-Hispanic whites (NHWs), and non-Hispanic blacks (NHBs). Yet,
      more often than not, OHISP have been merged with MA to form an all-Hispanic
      demographic group (HISP) thus limiting comparisons between NHW, NHB, and HISP.
      Consequently, for the first time, this study was undertaken to evaluate
      differences in the observed levels of selected environmental contaminants between
      MA and OHISP from five groups of environmental contaminants, namely, polycyclic
      aromatic hydrocarbons (PAHs), iodine uptake inhibitors (IUIs), environmental
      phenols (EPHs), priority pesticides (PPs), and perfluoroalkyl acids (PFAAs). Data
      for 2007-2010 from NHANES were used to conduct this study. OHISP children born in
      USA had higher levels of selected PAH metabolites than USA-born MA, and Mexican
      born MA adolescents had higher levels of selected PAH metabolites than USA-born
      MA adolescents. USA-born adolescent MA had higher levels of selected parabens
      than USA-born adolescent OHISP, and OHISP adults born in another Spanish-speaking
      country had higher levels of selected parabens than USA-born OHISP adults. USA
      born MA adults and seniors had higher levels of selected dichlorophenols than
      Mexico-born MA adults and seniors, respectively. Females had higher levels of
      selected PAH metabolites, EPHs, and PPs than males among children, adolescents,
      adults, and seniors, but the reverse was true for the levels of selected IUIs and
      PFAAs among adolescents and seniors. Smokers had higher levels of almost all PAH
      metabolites than non-smokers for adolescents, adults, and seniors. The same was
      true for urinary thiocynate for adolescents, adults, and seniors. OHISP is a
      multiracial multiethnic demographic group substantially different from MA with
      possibly different smoking behavior and with possibly differential levels of
      exposure to certain environmental contaminants and as such should be treated as a
      demographic group by itself.

PMID- 29188597
TI  - Association of urinary concentrations of four chlorophenol pesticides with
      cardiometabolic risk factors and obesity in children and adolescents.
AB  - This study was undertaken to determine the association of four chlorophenol
      pesticides with cardiometabolic risk factors and obesity in children and
      adolescents. This cross-sectional study was conducted in 2016 on 242 children and
      adolescents, aged 6 to 18 years. The concentrations of 2,4-dichlorophenol (2,4
      DCP), 2,5-dichlorophenol (2,5-DCP), 2,4,5-trichlorophenol (2,4,5-TCP), and 2,4,6
      trichlorophenol (2,4,6-TCP) in the urine were examined and their association with
      indices of obesity and cardiometabolic risk factors was determined. Multivariate
      linear regression and multinomial logistic regression analyses were applied.
      Overall, 242 participants with mean (SD) ages of 11.3 (2.5) years completed the
      survey. After adjustment for confounders, a significant positive association was
      found between body mass index (BMI) z-score and waist circumference (WC) with 2,5
      DCP (0.07 (95% CI 0.04, 0.1)) and 0.79 (95% CI 0.54, 1.03), respectively. A
      significant association of 2,4,5-TCP was only found with WC (0.23 (95% CI 0.0,
      0.46), but the relationship with 2,4-DCP was not significant. 2,5-DCP had a
      significant relationship only with obesity (1.09 (95% CI 1.1, 1.19)), while 2,4
      DCP and 2,4,5-TCP showed no significant correlation with overweight or obesity.
      2,4-DCP showed a significant positive relationship with high density lipoprotein
      cholesterol (HDL-C). Moreover, 2,5-DCP showed a significant negative relationship
      only with systolic blood pressure and 2,4,5-TCP had a statistically significant
      inverse association with total cholesterol and HDL-C (-0.71 (95% CI -0.98, 
      0.45)). This study suggests potential associations of chlorophenol pesticides
      with overweight, obesity, lipid profile, and blood pressure in children and
      adolescents. Longitudinal studies are necessary to assess the clinical impact of
      these findings.

PMID- 29188598
TI  - Influence of Phoslock(r) on legacy phosphorus, nutrient ratios, and algal
      assemblage composition in hypereutrophic water resources.
AB  - Acceleration of eutrophication in freshwater resources can result in prolific
      growth of nuisance algae, notably cyanobacteria. In this research, we evaluated
      the ability of an in situ P binding technology (Phoslock(r)) to alter available
      water column and sediment P, and the subsequent impact on nutrient ratios and
      algal assemblage composition. Two golf course irrigation ponds with legacy
      nutrient loads and chronic cyanobacterial blooms were treated with Phoslock and
      monitored for 2 years post-treatment. Phoslock significantly (P < 0.05) decreased
      water column total P levels and shifted mobile sediment P fractions (i.e.,
      labile, reductant-soluble, organic) to the residual fraction. Total N/P ratios
      (by mass) significantly increased and were sustained at over 30:1 in the Hickory
      Meadows irrigation pond and 100:1 in the Chockyotte irrigation pond throughout
      the study. Consequent changes in the algal assemblage included decreases in
      dominance and overall density of cyanobacteria as well as a shift away from scum
      forming genera (e.g., Microcystis spp. and Anabaena [Dolichospermum] sp.) to
      planktonic forms (e.g., Pseudanabaena sp. and Planktolyngbya sp.). This research
      provides information regarding mitigation of in situ water and sediment P toward
      shifting nutrient ratios and altering algal assemblage composition.

PMID- 29188600
TI  - Killing two birds with one stone: The multifunctional roles of mesenchymal stem
      cells in the treatment of neurodegenerative and muscle diseases.
AB  - Neurodegenerative and muscle diseases bear both complex and multifactorial
      pathologies. An efficacious and robust therapeutic option to treat these diseases
      is yet to be elucidated. At such a time, mesenchymal stem cells have drawn
      significant attention due to their immunomodulatory and regenerative properties.
      Accumulating evidence has proposed the capability of MSCs to serve multiple roles
      in a broad spectrum of diseases by secretion of trophic or paracrine factors. In
      the present review, we will look into the recent literature and discuss the
      therapeutic functions of MSCs and their potential to treat various
      neurodegenerative (Alzheimer's, Parkinson's, and Huntington's disease) and muscle
      (Duchenne muscular dystrophy, myopathy, and multiple sclerosis) diseases.

PMID- 29188599
TI  - Chemical characterization of PM2.5 collected from a rural coastal island of the
      Bay of Bengal (Bhola, Bangladesh).
AB  - This work focuses on the chemical characterization of fine aerosol particles
      (PM2.5) collected from a rural remote island of the Bay of Bengal (Bhola,
      Bangladesh) from April to August, 2013. PM2.5 particle-loaded filters were
      analyzed for organic carbon (OC), elemental carbon (EC), water-soluble ions, and
      selected saccharides (levoglucosan, mannosan, galactosan, arabitol, and
      mannitol). The average PM2.5 mass was 15.0 +/- 6.9 MUg m-3. Organic carbon and
      elemental carbon comprised roughly half of the analyzed components. Organic
      carbon was the predominant contributor to total carbon (TC) and accounting for
      about 28% of PM2.5 mass. Secondary organic carbon (SOC) was inferred to be ~ 26%
      of OC. The sum of ions comprised ~ 27% of PM2.5 mass. The contribution of sea
      salt aerosol was smaller than expected for a sea-near site (17%), and very high
      chloride depletion was observed (78%). NssSO42- was a dominant ionic component
      with an average concentration of 2.0 MUg m-3 followed by Na+, NH4+, and nssCa2+.
      The average concentration of arabitol and mannitol was 0.11 and 0.14 MUg m-3,
      respectively, while levoglucosan and its stereoisomers (mannosan and galactosan)
      were bellow detection limit. NH4+/SO42- equivalent ratio was 0.30 +/- 0.13
      indicating that secondary inorganic aerosol is not the main source of SO42-.
      Enrichment factor (EF) analysis showed that SO42- and NO3- were enriched in
      atmospheric particles compared to sea aerosol and soil indicating their
      anthropogenic origin. Higher OC/EC ratio (3.70 +/- 0.88) was a good indicator of
      the secondary organic compounds formation. Other ratios (OC/EC, K+/EC, nssSO42
      /EC) and correlation analysis suggested mixed sources for carbonaceous
      components. Arabitol and mannitol both showed strong correlation with EC having R
      2 value 0.89 and 0.95, respectively. Air mass trajectories analysis showed that
      concentrations of soil and anthropogenic species were lower for air masses
      originating from the sea (May-August) and were higher when air came from land
      (April).

PMID- 29188601
TI  - [Analysis of SCN1A deletions or duplications in patients with Dravet syndrome].
AB  - OBJECTIVE: To determine the type and frequency of SCN1A deletions and
      duplications among patients with Dravet syndrome (DS). METHODS: For DS patients
      in which no mutations of the SCN1A gene were detected by PCR-DNA sequencing,
      SCN1A deletions and duplications were detected by multiplex ligation-dependent
      probe amplification (MLPA). RESULTS: In 680 DS patients, 489 had SCN1A mutations
      identified by PCR-DNA sequencing. In 191 patients who were negative for the SCN1A
      PCR-DNA sequencing, 15 (15/191, 7.9%) were detected with heterozygous SCN1A
      deletions or duplications, which included 14 (14/15, 93.3%) SCN1A deletions and 1
      SCN1A duplication. There were 13 types of mutations, including whole SCN1A
      deletions in 3 patients, partial SCN1A deletions in 11 patients and partial SCN1A
      duplications in one patient. By testing the parents, 14 mutations were found to
      be de novo. For the remaining case, no SCN1A deletion or duplication was found in
      the mother, while the father was not available. CONCLUSION: Approximately 8% of
      Chinese patients who were negative for SCN1A mutation by PCR-sequencing have
      SCN1A deletions or duplications. The MLPA analysis should be considered as an
      important strategy for such patients. SCN1A deletions are more common than SCN1A
      duplications among DS patients, and the most common types are whole SCN1A
      deletions. The majority of SCN1A deletions or duplications are de novo.

PMID- 29188602
TI  - [Rare thalassemia mutations among southern Chinese population].
AB  - OBJECTIVE: To detect rare types of thalassemia mutations among southern Chinese
      population. METHODS: Peripheral blood samples from 327 patients from various
      regions of southern China were collected. The patients were suspected as rare
      type thalassemia for their inconsistency between hematological phenotypes and
      results of routine mutation screening. The samples were further analyzed with GAP
      PCR and DNA sequencing. RESULTS: One hundred and eight cases were diagnosed as
      rare types of thalassemia. Among whom 10 rare alpha-globin gene mutations
      including --THAI, HKalpha, alphaalphaalphaanti3.7, alphaalphaalphaanti4.2, 
      alpha2.8, -alpha27.6, CD74 GAC>CAC (Hb Q-Thailand), CD30 (-GAG), CD31 AGG>AAG and
      CD118 (+TCA), and 12 rare beta-globin gene mutations including CD37 TGG>TAG, CD39
      CAG>TAG/CD39 CAG>TAG, beta II-2 (-T), -90(C>T), -31(A>C), -88(C>T), CD7(-A),
      CD138(+T), CD89-93 (--AGTGAGCTGCACTG), CD54-58 (-TATGGGCAACCCT), Chinese G gamma
      +(A gammadeltabeta)0 and Vietnamese HPFH (HPFH-6) were identified. -88(C>T) (HBB:
      c.-138C>T) and CD39 CAG>TAG (HBB: c.118C>T) were discovered for the first time in
      Chinese population. CD7(-A) (HBB: c.23delA) and CD138(+T) (HBB: c.416_417insT)
      were new types of beta-globin gene mutations. CONCLUSION: The present study have
      enriched the mutation spectrum of thalassemia in southern China, which has
      provided necessary information for its diagnosis.

PMID- 29188603
TI  - [Genetic mutation and clinical features of osteogenesis imperfecta type V].
AB  - OBJECTIVE: To explore genetic mutations and clinical features of osteogenesis
      imperfecta type V. METHODS: Clinical record of five patients (including one
      familial case) with osteogenesis imperfecta type V were retrospectively analyzed.
      Peripheral blood samples of the patients, one family member, as well as healthy
      controls were collected. Mutation of IFITM5 gene was identified by PCR
      amplification and Sanger sequencing. RESULTS: A heterozygous mutation (c.-14C>T)
      in the 5-UTR of the IFITM5 gene was identified in all of the patients and one
      mother. The clinical findings included frequent fractures and spine and/or
      extremities deformities, absence of dentinogenesis imperfecta, absence of hearing
      impairment, and blue sclera in 1 case. Radiographic findings revealed
      calcification of the interosseous membrane between the radius-ulna in all cases.
      Hyperplastic callus formation was found in 3 cases. Four had radial-head
      dislocation. CONCLUSION: A single heterozygous mutation c.-14C>T was found in the
      5-UTR of the IFITM5 gene in 5 patients with osteogensis imperfecta type V. The
      patients showed specific radiological features including calcification of
      interosseous membrane, hyperplastic callus formation, and radial-head
      dislocation.

PMID- 29188604
TI  - [Analysis of 12 patients with novel mutations of Dystrophin gene].
AB  - OBJECTIVE: To study the characteristics, location, and amino acid changes of
      novel mutations of the Dystrophin gene. METHODS: Twelve patients in whom no
      deletion or duplication of the Dystrophin gene was detected were analyzed with
      next-generation sequencing. Fifty healthy adult males were recruited as the
      controls. RESULTS: All patients were detected with mutations of the Dystrophin
      gene, which included c.33C>G, c.583C>T, c.1333C>T, c.2593C>T, c.5731A>T,
      c.7288G>T, c.2803+1G>T, c.10034G>A, c.4289A>G, c.1905_906delAG, c.5017delC,
      c.5768_5771delAAGA, and c.6261_6262insA. No similar mutations were found among
      the controls. CONCLUSION: Our data has enriched the mutation spectrum of the
      Dystrophin gene and may provide an important basis for genetic diagnosis.

PMID- 29188605
TI  - [Analysis of prognosis of acute myeloid leukemia patients based on genetic
      mutations].
AB  - OBJECTIVE: To correlate the clinical features of patients with acute myeloid
      leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4
      genes as well as chromosomal aberrations. METHODS: Somatic mutations of
      aforementioned genes in 412 newly diagnosed AML patients were detected with PCR
      and direct sequencing. All patients were also subjected to R-banding chromosomal
      analysis. The results were correlated with the clinical features and prognosis of
      the patients. RESULTS: The mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A
      and ND4 were 9.0% (26/289), 19.1% (50/262), 18.9% (34/180), 3.4% (7/208), 6.6%
      (9/137) and 6.9% (4/58), respectively. Patients with poor prognosis based on
      genetic mutations had lower blood platelet count than those with intermediate and
      good prognosis (P=0.001 and P=0.001, respectively). None of the three groups
      attained median overall survival (OS) (P> 0.05). The complete remission (CR) was
      similar among the three groups (P> 0.05). For patients with different prognosis
      based on cytogenetic findings, white blood cell count in those with intermediate
      prognosis was higher than those with good and poor prognosis (P< 0.001 and
      P=0.004, respectively), while the blood platelet count of the intermediate group
      was higher than that of the group with good prognosis (P=0.018). No significant
      difference was found among the three groups in terms of hemoglobin level (P>
      0.05). The group with poor prognosis has attained shorter OS compared with those
      with good and intermediate prognosis (P< 0.001 and P=0.003, respectively).
      However, the CR rate of the group with good prognosis was higher than that of the
      intermediate group (P=0.001). For the group with intermediate prognosis, presence
      of genetic mutations did not correlate with the clinic characteristics such as
      white blood cell count, blood platelet count, hemoglobin level, OS and CR rate
      (P> 0.05 for all comparisons). CONCLUSION: Genetic mutations combined with
      cytogenetic analysis can facilitate the prognosis and personalized treatment for
      patients with AML.

PMID- 29188606
TI  - [Chromosome microarray analysis of four fetuses with abnormal karyotypes].
AB  - OBJECTIVE: To carry out chromosomal microarray analysis (CMA) on four fetuses
      with abnormal karyotypes. METHODS: Amniotic fluid samples were obtained and
      subjected to routine G-banded karyotyping analysis. CMA was applied for cultured
      amniocytes to determine alterations of gene dosage and chromosomal breakpoints.
      RESULTS: Abnormal karyotypes were found in the parents of 3 fetuses. Parental
      karyotypes of the remaining fetus were normal. Imbalance chromosome
      rearrangements were revealed by CMA in all 4 cases. CONCLUSION: CMA is an
      effective tool for the evaluation of clinical significance and delineation of the
      breakpoints involved in complex chromosomal rearrangements.

PMID- 29188607
TI  - [NOTCH3 gene mutations in two Chinese families featuring cerebral autosomal
      dominant arteriopathy with subcortical infarct and leucoencephalopathy].
AB  - OBJECTIVE: To analyze potential mutations of the NOTCH3 gene in two Chinese
      families featuring cerebral autosomal dominant arteriopathy with subcortical
      infarct and leucoencephalopathy (CADASIL). METHODS: The two probands and related
      family members and 100 healthy controls were recruited. Potential mutations of
      the NOTCH3 gene were screened by PCR and direct sequencing. PolyPhen-2 and SIFT
      software were used to predict the protein function. RESULTS: The conditions of
      both probands were adult-onset, with main clinical features including recurrent
      transient ischemic attacks and/or strokes, cognitive impairment. MRI findings
      suggested multiple cerebral infarcts and severe leukoencephalopathy. A
      heterozygous mutation c.328C>T (p.Arg110Cys), which was located in exon 3 of the
      NOTCH3 gene and known as a causative mutation, was identified in proband 1. A
      novel heterozygous mutation c.1013 G>C (p.Cys338Ser) located in exon 6 of the
      NOTCH3 gene was identified in the proband 2, which was not reported previously.
      The same mutations were not detected among the 100 unrelated healthy controls.
      Function analysis suggested that heterozygous mutation c.1013G>C can severely
      affect the functions of NOTCH3 protein. CONCLUSION: Two heterozygous missense
      mutations in the NOTCH3 gene have been identified in two families affected with
      CADASIL. The novel heterozygous Cys338Ser mutation in exon 6 of the NOTCH3 gene
      probably underlies the CADASIL.

PMID- 29188608
TI  - [CADASIL with clinical manifestations of baldness, lumbago and Parkinson's
      symptoms].
AB  - OBJECTIVE: To investigate a cerebral autosomal dominant arteriopathy with the
      subcortical infarcts and leukoencephalopathy (CADASIL) case with clinical
      manifestations of baldness, lumbago and Parkinson's symptoms. METHODS: Clinical
      and imaging data of the patient were analyzed. The patient and his family members
      were also subjected to genetic testing. RESULTS: The symptoms of the patient
      included recurrent stroke, dementia, and mood disturbance, in addition with
      lumbago, baldness and Parkinson's symptoms but no migraine. Cranial MRI of the
      patient showed bilateral symmetric leukoencephalopathy and multiple small
      subcortical lacunar infarcts. A point mutation in exon 11 of the NOTCH3 gene
      (R558C) was discovered in the proband and four asymptomatic relatives.
      CONCLUSION: CADASIL is characterized by recurrent subcortical ischemic stroke,
      dementia, pseudobulbar palsy, and mood disturbance. Baldness, lumbago and
      Parkinson's symptoms may also be seen in such patients.

PMID- 29188609
TI  - [Clinical and genetic analysis of two unrelated patients with Angelman syndrome
      and novel UBE3A mutations].
AB  - OBJECTIVE: To explore the genetic cause for two familial Angelman syndrome cases
      and correlation between the clinical phenotypes and their genetic basis. METHODS:
      Karyotyping analysis and microarray assay were carried out to exclude chromosome
      anomalies and uniparental disomy. The UBE3A gene was analyzed for potential point
      mutations, deletions, insertions and splice site mutations. Reverse transcription
      PCR was used to evaluate splicing mutation of the RNA transcripts. RESULTS: DNA
      sequencing showed the proband of family 1 has carried a novel maternal UBE3A
      splice acceptor site mutation, resulting in a guanine-to-cytosine transversion
      (IVS15-1G>C). Reverse transcription PCR revealed the proband and his mother both
      carried heterozygous mutant transcripts with loss of 54 and 59 nucleotides in
      exon 16, respectively. The proband displayed severe mental retardation, ataxia,
      seizures and inappropriate laughter. The siblings of family 2 has carried a novel
      maternal missense mutation in exon 16 of the UBE3A gene (c.2540C>T). She also
      presented with mental retardation, absent speech, mild ataxia and inappropriate
      laughter. CONCLUSION: The novel IVS15-1G>C and c.2540 C>T mutations of the UBE3A
      gene probably underlie the AS in the two families. Compared with small-scale
      mutations, larger fragments mutations can produce more severe phenotypes.

PMID- 29188610
TI  - [Genetic analysis of two pediatric patients with Beckwith-Wiedemann syndrome].
AB  - OBJECTIVE: To explore the genetic cause for two children with omphalocele.
      METHODS: The patients were examined, and the medical history of their families
      was collected. Methylation-specific multiplex ligation-dependent probe
      amplification (MS-MLPA) was performed to detect potential mutation in the
      patients. RESULTS: Loss of methylation of imprinting center 2 (IC2) at the
      11p15.5 region of the maternal chromosome was detected in both children.
      CONCLUSION: The two patients were diagnosed with Beckwith-Wiedemann syndrome by
      MS-MLPA. The loss of methylation of IC2 probably underlies the disease in both
      patients.

PMID- 29188611
TI  - [Application of next generation sequencing for the analysis of patients with
      spontaneous abortion].
AB  - OBJECTIVE: To assess the value of next generation sequencing (NGS) for the
      analysis of spontaneous abortion samples. METHODS: The NGS analysis was carried
      out on 85 chorionic villi samples (taken between 42 days to 12 weeks of
      gestation) for which conventional cell culture has failed or chromosomal
      karyotyping has yielded normal or uncertain result. RESULTS: Among 68 samples
      with a normal karyotype, the NGS analysis has identified 2 copy number variations
      (CNVs) and 2 chimeras. For 16 cases with failed cell culture, the NGS has
      identified 4 chromosomal abnormalities including 1 copy number variation and 3
      numerical chromosomal aberrations. For 1 remaining case with uncertain
      karyotyping result, the NGS analysis has verified it as 46,XX,del(4)
      (p15.1p16.3).seq[GRCh37/hg19] (57 549 - 32 371 364)*1. CONCLUSION: The NGS
      analysis is capable of identifying novel CNVs in samples for which conventional
      cell culture may fail or karyotyping analysis may yield a normal result.

PMID- 29188612
TI  - [Influence of CYP2C19 gene polymorphisms on the efficacy of clopidogrel treatment
      for the prevention of ischemic stroke following coronary stent implantation].
AB  - OBJECTIVE: To assess the association of CYP2C19 gene polymorphisms with the
      incidence of ischemic stroke among patients receiving clopidogrel therapy
      following coronary stenting for coronary artery disease. METHODS: Clinical data
      of patients receiving clopidogrel therapy after coronary stenting were
      retrospectively studied. For a case-control study, 137 patients with acute
      cerebral infarction and 122 non-stroke patients were selected. Based on the
      variants of the CYP2C19 gene detected by a DNA microarray assay, the patients
      were further divided into the wild-type group(CYP2C19*1/*1) and mutant
      group(defined by the presence of at least one loss-of-function allele, including
      CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3). The
      incidences of ischemic stroke in the two groups were compared through a chi
      square analysis. The influence of CYP2C19 gene polymorphisms and clopidogrel
      therapy on the incidence of ischemic stroke was analyzed through multivariable
      logistic regression. RESULTS: A total of 259 patients were enrolled. The case and
      control groups showed no difference in terms of gender and age. There were 123
      cases (47.5%) in the CYP2C19 wild-type group and 136 cases (52.5%) in the mutant
      group. The incidence of ischemic stroke of mutant group was significantly higher
      than that of wild-type group (59.9% vs. 44.3%, X2=6.398, P=0.042). Multivariate
      analysis revealed that loss-of-function polymorphisms of the CYP2C19 gene carried
      a 1.13 times greater risk for ischemic stroke compared to wild-type genotype
      (OR=2.13, 95%CI: 1.23-3.71). CONCLUSION: The efficacy of clopidogrel for the
      prevention of ischemic stroke in post-coronary stent patients may be reduced by
      the insufficiency of the CYP2C19 gene. The dosage of clopidogrel therapy should
      be adjusted based on its polymorphisms.

PMID- 29188613
TI  - [Exploration of common biological pathways for attention deficit hyperactivity
      disorder and low birth weight].
AB  - OBJECTIVE: To explore common biological pathways for attention deficit
      hyperactivity disorder (ADHD) and low birth weight (LBW). METHODS: Thei
      Gsea4GwasV2 software was used to analyze the result of genome-wide association
      analysis (GWAS) for LBW (pathways were derived from Reactome), and nominally
      significant (P< 0.05, FDR< 0.25) pathways were tested for replication in
      ADHD.Significant pathways were analyzed with DAPPLE and Reatome FI software to
      identify genes involved in such pathways, with each cluster enriched with the
      gene ontology (GO). The Centiscape2.0 software was used to calculate the degree
      of genetic networks and the betweenness value to explore the core node (gene).
      Weighed gene co-expression network analysis (WGCNA) was then used to explore the
      co-expression of genes in these pathways.With gene expression data derived from
      BrainSpan, GO enrichment was carried out for each gene module. RESULTS: Eleven
      significant biological pathways was identified in association with LBW, among
      which two (Selenoamino acid metabolism and Diseases associated with
      glycosaminoglycan metabolism) were replicated during subsequent ADHD analysis.
      Network analysis of 130 genes in these pathways revealed that some of the sub
      networksare related with morphology of cerebellum, development of hippocampus,
      and plasticity of synaptic structure. Upon co-expression network analysis, 120
      genes passed the quality control and were found to express in 3 gene modules.
      These modules are mainly related to the regulation of synaptic structure and
      activity regulation. CONCLUSION: ADHD and LBW share some biological regulation
      processes. Anomalies of such proces sesmay predispose to ADHD.

PMID- 29188614
TI  - [Clinical and genetic analysis of a boy with 9q34.3 microdeletion syndrome].
AB  - OBJECTIVE: To determine the origin of chromosomal aberration in a boy with mental
      retardation and multiple congenital malformations. METHODS: The karotypes of the
      proband and his parents were analyzed with conventional G-banding. Their genomic
      DNA was analyzed with array comparative genomic hybridization (aCGH). RESULTS: No
      karyotypic abnormality was detected in the proband and his parents. aCGH has
      identified a de novo 405 kb deletion at 9q34.3 in the proband, which encompassed
      the EHMT1 gene and part of CACNA1B gene. CONCLUSION: The de novo 9q34.3 deletion
      probably underlies the mental retardation and development delay in the boy. EHMT1
      may be one of the key genes responsible for 9q34.3 microdeletion syndrome.

PMID- 29188616
TI  - [Prenatal diagnosis of a tetrasomy 18p case using BACs-on-Beads technology and
      single nucleotide polymorphism array].
AB  - OBJECTIVE: To determine the origin of a supernumerary small marker chromosome
      found in a fetus using prenatal BACs-on-Beads (BoBs) and single nucleotide
      polymorphism array (SNP-array) assays. METHODS: The fetal sample was subjected to
      chromosomal karyotyping and BoBs analysis, and the results were validated with
      genome-wide scanning using a SNP microarray. RESULTS: The fetus was found to have
      a 47,XX,+mar karyotype. BoBs analysis indicated that there was an amplification
      between 18p11.32 and 18p11.21, which was verified by the SNP-array assay as a
      18.3 Mb duplication occurring at 18p11.32q11.1. CONCLUSION: The karyotype of the
      fetus was determined as 47,XX,+der18(18p11.32?18q11.1::18q11.1?18p11.32). The
      duplication has involved important genes including SMCHD1, LPIN2 and TGIF1, which
      may result in severe malformations in the fetus.

PMID- 29188615
TI  - [Prenatal diagnosis of two fetuses with chromosome 1p36 deletion syndrome].
AB  - OBJECTIVE: To analyze two fetuses with multiple malformations revealed by
      ultrasonography using single nucleotide polymorphism array (SNP array), and to
      explore the strategy for the prenatal diagnosis of 1p36 deletion syndrome.
      METHODS: Amniocentesis was performed on the two pregnant women. Amnion fluid
      cells were cultured, and karyotypes of the fetuses were determined through G
      banding analysis. Whole genome SNP array was used to detect genomic anomalies of
      the two fetuses. The karyotypes of their parents were determined through G
      banding analysis of peripheral venous blood samples. RESULTS: G-banding analysis
      showed a 46,XY,add(1p36)? and a 46,XX,add(1p36)? karyotype for fetuses 1 and 2,
      respectively. SNP array analysis showed that the fetus 1 had arr[19]1p36.33p36.32
      (752 566 - 3 393 462)*1 and 7q35q36.3 (144 480 549 - 159 119 486)*3, and fetus 2
      had arr[19]1p36.33p36.23 (752 566 - 8 362 754)*1, 6p25.3p22.3 (204 909 - 20 182
      185)*3. The mother of fetus 1 had a 46,XX,t(1;7)(p36;q35) karyotype, and the
      mother of fetus 2 had a 46,XX,t(1;6)(p36;p22) karyotype. The karyotypes of both
      fathers appeared to be normal. CONCLUSION: SNP array has the advantages such as
      high sensitivity and high accuracy for prenatal diagnosis, and can provide more
      detailed information for genetic counseling of 1p36 deletion syndrome.

PMID- 29188617
TI  - [SNP array analysis of three cases with partial 21q trisomy].
AB  - OBJECTIVE: To analyze three cases with partial 21q trisomy, and correlate their
      genotypes with phenotypes. METHODS: G-banding chromosomal analysis and single
      nucleotide polymorphism (SNP array) were performed for the three cases and their
      parents. RESULTS: SNP array has detected partial 21q trisomy in three cases and
      one mother, with variable size and location of the duplications. Case 1 harbored
      a 12.35 Mb duplication at 21q22.11q22.3, which spanned the Down syndrome critical
      region. Case 2 harbored a 35.32 Mb duplication at 9p24.3p13.3 and a 14.42 Mb
      duplication at 21q11.2q21.3, with the former spanning the partial 9p trisomy
      syndrome critical region excluding the Down syndrome critical region, and was
      inherited from his mother. Case 3 harbored a 4.17 Mb tetraploidy at 21q11.2q21.1
      in the form of mosaicism, which spared the Down syndrome critical region. His
      mother carried a 4.17 Mb triploidy at 21q11.2q21.1, which was also a mosaicism.
      CONCLUSION: Partial 21q trisomy may occur in various forms and its clinical
      phenotypes are heterogeneous. Combined use of genetic techniques, particularly
      SNP array, is crucial for diagnosing partial 21q trisomy and delineating its
      genotype-phenotype correlation.

PMID- 29188618
TI  - [Identification of novel compound heterozygous mutations in the ANTXR2 gene in a
      Chinese patient with juvenile hyaline fibromatosis].
AB  - OBJECTIVE: To identify pathogenic mutations of ANTXR2 gene in a patient with
      juvenile hyaline fibromatosis. METHODS: Genomic DNA was extracted from peripheral
      venous blood sample from the patient. All coding exons (exons 1-17) and splicing
      sites of the ANTXR2 gene were amplified with PCR. Potential mutations were
      detected with direct sequencing of the PCR products. 100 unrelated healthy
      subjects were used as the controls. CLUSTALX (1.81) was employed to analyze cross
      species conservation of the mutant amino acid. Impact of the mutations was
      analyzed with software including SIFT, PolyPhen-2 and MutationTaster. RESULTS: A
      compound heterozygous mutation c.1074delT/c.1153G>C, was identified, among which
      c.1153G>C has not been reported previously and was predicted to be probably
      damaging. Both mutations were not found among the 100 healthy controls.
      CONCLUSION: The patient's condition may be attributed to the compound
      heterozygous mutations of c.1074delT and c.1153G>C of the ANTXR2 gene. Above
      results has facilitated molecular diagnosis for this patient.

PMID- 29188619
TI  - [Detection and prenatal diagnosis of TOR1A gene mutation in a Chinese family
      affected with dystonia].
AB  - OBJECTIVE: To explore the feasibility of using PCR-based capillary
      electrophoresis method to analysis mutation of the TOR1A gene in a family
      affected with primary torsion dystonia (PTD). METHODS: Peripheral blood sample
      was collected from proband and amnionic fluid from her fetus for the extraction
      of DNA. The 5th exon of the TOR1A gene and its flanking sequences were amplified
      with PCR and analyzed with agarose electrophoresis, fluorescence labeled fragment
      analysis and Sanger sequencing. RESULTS: Fluorescence labeled fragment analysis
      was performed through capillary electrophoresis, which showed that the proband
      carried a c.907_909delGAG (p.Glu303del) deletional mutation of the TOR1A gene.
      The result was verified by Sanger sequencing. The fetus DNA was also found with
      the same mutation by capillary electrophoresis, inferring that the fetus was
      probably affected with the disease. CONCLUSION: The mutation of c.907_909delGAG
      of the TOR1A gene was speculated as pathologic cause of proband in this family.
      Fragment analysis by capillary electrophoresis combined with DNA sequencing is an
      efficient test for small deletional mutations and feasible for its prenatal
      diagnosis.

PMID- 29188620
TI  - [Analysis of genotype and phenotype of SEC23B gene in a family affected with
      congenital dyserythropoietic anemia type II].
AB  - OBJECTIVE: To detect potential mutation in a family affected with congenital
      dyserythropoietic anemia type II (CDA II). METHODS: Targeted sequence capture and
      next-generation sequencing (NGS) were used to analyze the exons and exon-intron
      boundaries of the SEC23B gene in a clinically suspected CDA II patient. Genotypes
      of the relatives were validated by Sanger sequencing. Potential impact of amino
      acid substitution on the structure and function of SEC23B protein was predicted
      with MutationTaster and PolyPhen-2. The protein structure was predicted with
      SWISS-MODEL software. RESULTS: The proband was found to harbor double
      heterozygous mutations of the SEC23B gene, c.1727T>C (p.F576S) and c.1831C>T
      (p.R611W), which resulted in amino acid substitutions p.F576S and p.R611W. Both
      mutations were confirmed by Sanger sequencing. The sister of the proband was
      found to have carried c.1727T>C (p.F576S), while her father and son have carried
      c.1831C>T (p.R611W) mutation. In addition, the proband was detected to have
      carried c.211C>T (p.R71X) of the HFE gene, which resulted in substitution of
      arginine by a stop codon. The impact of above mutations on the structure or
      function of protein was predicted to be harmful. Splenectomy and iron chelation
      therapy have achieved effective improvement of anemia and iron overload. Computer
      simulation suggested that the mutations have altered the 3D structure of the
      SEC23B protein. CONCLUSION: The novel compound mutations of c.1727T>C and
      c.1831C>T of the SEC23B gene probably underlie the CDA II in the family, and
      there is a strong correlation between the genotype and phenotype.

PMID- 29188621
TI  - [Prenatal diagnosis of a fetus with Miller-Dieker syndrome].
AB  - OBJECTIVE: To report on prenatal diagnosis of a fetus with Miller-Dieker syndrome
      (MDS) and explore its genotype - phenotype correlation. METHODS: Chromosome
      karyotyping, bacterial artificial chromosome on beads (BACs-on-Beads, BoBs),
      fluorescence in situ hybridization (FISH), and single nucleotide polymorphism
      microarray (SNP array) were applied in conjunction for the prenatal diagnosis of
      a fetus with abnormal ultrasound findings. RESULTS: A 17p13.3 microdeletion was
      detected with the BoBs assay, and the result was confirmed by FISH. With the SNP
      array, the deletion was mapped to chromosome 17, with its range determined to be
      5.2 Mb. On high-resolution banding analysis and BoB assay, the deletion was not
      found in either parent. CONCLUSION: The combined use of BoBs, FISH and SNP array
      has enabled prenatal diagnosis of a fetus with MDS. Attention should be paid to
      microdeletions and microduplications which can be missed by conventional
      chromosomal karyotyping analysis.

PMID- 29188622
TI  - [Two false negative cases in noninvasive prenatal testing for fetal chromosomal
      aneuploidies].
AB  - OBJECTIVE: To explore the limitation of non-invasive prenatal testing (NIPT)
      technique through analyzing two false negative cases. METHODS: Chromosomal
      karyotyping analysis was performed on umbilical cord blood sample derived from
      case 1 at 24 weeks' gestation and peripheral blood sample derived from the
      neonate of case 2. Placental tissues of case 1 and peripheral blood sample of
      case 2 were also analyzed by high-throughput sequencing for copy number
      variations (CNVs). RESULTS: For case 1, analysis of fetal umbilical cord blood
      sample showed a translocation type of trisomy 21, i.e.,
      46,XY,der(21;21)(q10;q10),+21. There were no obvious abnormalities detected at or
      near the center of the fetal surface and matrix surface of the placenta. High
      thoroughput sequencing showed Chr13:(33 840 001 - 115 100 000)*3[60%]/46,XY[40%]
      at the edge of the placenta, Chr13:(34 080 001-115100000)*3[54%]/46,XY[46%] at
      the edge of placenta matrix surface, and trisomy 21 in the umbilical cord tissue.
      For case 2, analysis of the neonatal peripheral blood sample showed a karyotype
      of 46,XY,del(18)(q22), which revealed a microdeletion in chromosome 18. High
      throughput sequencing of the maternal peripheral blood sample stored during
      pregnancy confirmed it to be chr18: (62 910 000 - 78 020 000)*1 with 15.1 Mb
      deletion in the fetus. The neonate was therefore diagnosed with partial monosomy
      of chromosome 18. CONCLUSION: False negative results of NIPT are related with the
      fraction of circulating cell-free fetal DNA in the maternal serum. NIPT has
      limitations in detecting fetal chromosomal microdeletion and confined placenta
      mosaicisms. Routine ultrasound scan is necessary for pregnant women with low-risk
      indicated by NIPT.

PMID- 29188623
TI  - [Pedigree investigation and genetic analysis of a case with Vel heterozygous
      deletion mutation].
AB  - OBJECTIVE: To analyze an individual with SMIM1 c.64_80 heterozygous deletional
      mutation and his family members. METHODS: Based on the molecular basis of Vel
      negative blood type, PCR primers specific for SMIM1 wild-type allele and
      c.64_80del allele were designed. PCR-sequence specific primer (PCR-SSP) and
      Sanger sequencing were employed to determine the genotype of all subjects.
      Inheritance of the Vel blood group system was investigated by pedigree analysis.
      RESULTS: PCR-SSP and DNA sequencing demonstrated that the proband was
      heterozygous for the SMIM1 c.64_80del allele. Pedigree investigation showed that
      his father had the same mutation, while his mother and elder sister were of wide
      type. No individual with homozygous c.64_80del allele was found. CONCLUSION: PCR
      SSP and DNA sequencing confirmed that the proband was heterozygous for the
      c.64_80del mutation. The mutation inherits form his father.

PMID- 29188624
TI  - [Identification of a novel Bx allele of the ABO blood group].
AB  - OBJECTIVE: To identify a novel Bx13 allele. METHODS: Serological characteristics
      was determined with standard serological methods. All of the seven exons and
      flanking regions of the ABO gene were analyzed with PCR and direct sequencing.
      The amplicon of exon 7 was also cloned and sequenced. RESULTS: The individual was
      determined as with a rare Bx phenotype by serological tests. Direct DNA
      sequencing showed that the individual was heterozygous for the B/O01 allele,
      while there was a novel 893C>T mutation in the B101 allele, which has led to an
      amino acid substitution Ala298Val in the alpha,3-D-galactosyl-transferase. The
      mutation was not found among 100 randomly selected blood donors. CONCLUSION: A
      novel Bx13 allele has been identified. Substitution of amino acid in the
      conserved region of the enzyme may reduce the activity of alpha,3-D-galactosyl
      transferase.

PMID- 29188625
TI  - [Identification of a novel ABO B(A)07 allele].
AB  - OBJECTIVE: To explore the molecular basis for a novel B(A) phenotype. METHODS:
      Genomic DNA was abstracted from peripheral blood sample from the proband. ABO
      genotyping were carried out with sequence specific primer PCR (PCR-SSP). Exons 6
      and 7 of the ABO gene were amplified with PCR and sequenced. RESULTS: Anti-A
      serum could not be adsorbed or eluted by the donor's red blood cells, and no
      irregular antibodies were found in the plasma. PCR-SSP showed that the ABO
      genotype of the donor was ABO *B/O. Sequencing results showed that one of the
      alleles was ABO *O02, while the other could not be defined but contained the
      following mutation points, 297A>G, 526C>G, 657C>T, 701C>T, 703G>A, 796C>A,
      803G>C, and 930G>A. The data was accepted by the GenBank (the loading code was
      KM974887) and the Blood Group Antigen Mutation Database, and was confirmed to be
      a novel allele of B(A). CONCLUSION: A novel allele ABO *B(A)07 with 701C>T has
      been identified, which may facilitate further study on blood antigen variants and
      typing of the blood groups.

PMID- 29188626
TI  - [Polymorphism of RHD gene among RhD negative and D variant blood donors from
      Qingdao region].
AB  - OBJECTIVE: To study the molecular mechanism and polymorphism of D gene of RhD
      negative and D variants among voluntary blood donors from Qingdao region.
      METHODS: For 220 D-negative phenotype cases and 5 D variant cases confirmed by
      serological test, exons 1 to 10 of the RHD gene were detected by a PCR-SSP
      method. The samples which contain all or part of the exons were sequenced.
      RESULTS: Among the 220 cases, 166 (75.45%) had complete absence of the RHD gene,
      while 54 (24.55%) had retained some or all of the 10 exons. Eight genotypes were
      identified, which included RHD 1227G>A in 28 cases (12.73%), RHD-CE- (2-9) -D in
      19 cases (8.64%), RHD-CE- (3-7)-D in 1 case (0.45%), RHD 3G>A in 1 case (0.45%),
      RHD 711delC in 2 cases (0.91%), RHD 845G>A in 1 case (0.45%), RHD 1013T>C in 1
      case (0.45%), and RHD 1227A/G in 1 case (0.45%). No mutation was found in all of
      the 10 exons. Two alleles were identified in the 5 cases of D variants, which
      included RHD 845G>A (4 cases) and RHD 697G>A (1 case). CONCLUSION: Absence of the
      whole RHD gene is common among RhD negative blood donors from Qingdao region, and
      there are rich genetic polymorphisms for this locus.

PMID- 29188627
TI  - [Association of aggressive behaviors of schizophrenia with short tandem repeats
      loci].
AB  - OBJECTIVE: To assess the association of short tandem repeats (STRs) loci with
      aggressive behaviors of schizophrenia. METHODS: Blood samples from 123
      schizophrenic patients with aggressive behaviors and 489 schizophrenic patients
      without aggressive behaviors were collected. DNA from all samples was amplified
      with a PowerPlex 21 system and separated by electrophoresis to determine the
      genotypes and allelic frequencies of 20 STR loci including D3S1368, D1S1656,
      D6S1043, D13S317, Penta E, D16S639, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA,
      D21S11, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, and FGA. RESULTS: All of
      the 20 STR loci have reached Hardy-Weinberg equilibrium in both groups. A
      significant difference was found in allelic and genotypic frequencies of loci
      Penta D between the two groups (alleles: P=0.042; genotypes: P=0.014) but not for
      the remaining 19 loci (P> 0.05). Univariate analysis also showed a significant
      difference for allele 10 and genotypes 10-12 of Penta D between the two groups
      (P=0.0027, P=0.0001), with the OR being 1.81 (95%CI: 1.22-2.67) and 4.33 (95%CI:
      1.95-9.59), respectively. CONCLUSION: Penta D may be associated with aggressive
      behaviors of schizophrenia. Allele 10 and genotypes 10-12 of Penta D may confer a
      risk for the disease.

PMID- 29188628
TI  - [Effect of MTHFR gene on the schizophrenia and its cognitive function].
AB  - OBJECTIVE: To investigate the effect of MTHFR gene on schizophrenia and its
      cognitive function. METHODS: We recruited 254 schizophrenia patients with stable
      condition, 339 healthy controls for genetic analysis and 72 healthy controls for
      cognitive evaluation. The repeatable battery for the assessment of
      neuropsychological status (RBANS) was used for cognitive measurement. PCR-RFLP
      technique was carried out to genotype 677C/T polymorphism. RESULTS: There were no
      significant differences in genotypic or allelic frequencies of the 677C/T
      polymorphism between the case and control groups (P> 0.05). In the RBANS,
      patients had higher scores of immediate memory, visuospatial skill, language,
      attention, delayed memory and total scores than healthy controls (P< 0.01);
      Patients with different genotypes of 677C/T polymorphism had significant
      differences in the scores of immediate memory, attention and total scores (P<
      0.05). CONCLUSION: Our results did not provide evidence for MTHFR gene conferring
      susceptibility to schizophrenia. However, there was a significant association
      between the MTHFR gene and cognitive impairment in patients with schizophrenia,
      especially in immediate memory and attention.

PMID- 29188629
TI  - [Association of HSPA1A gene single nucleotide polymorphisms with the development
      of cervical cancer among ethnic Han Chinese from Yunnan].
AB  - OBJECTIVE: To assess the association of four single nucleotide polymorphisms
      (SNPs) (rs12190359C>T, rs562047C>G, rs1008438G>T, and rs1043618G>C) of HSPA1A
      gene with the development of cervical cancer among ethnic Han Chinese from
      Yunnan. METHODS: One hundred and thirty patients with CIN III, 444 patients with
      cervical cancer, and 548 healthy individuals were recruited, and the genotypes of
      the above SNPs were determined with a Taqman assay. Haplotypes were constructed,
      and their association with the development of cervical cancer was analyzed.
      RESULTS: The frequencies of G and T alleles of rs1008438G>T were significant
      different between the CIN III and control groups, as well as between the cancer
      and control groups (P=0.022 and P=0.030, respectively). There was a significant
      difference in genotypic frequency of rs1008438G>T between the CIN III and control
      groups (P=0.047). The allelic and genotypic frequencies of rs12190359C>T,
      rs562047C>G, and rs1043618G>C did not significantly differ between the CIN III,
      cervical cancer and control groups (P> 0.05). The frequencies of haplotypes
      formed by rs562047C>G, rs1008438G>T and rs1043618G>C also did not significantly
      differ between the CIN III, cancer and control groups (P> 0.05). CONCLUSION: The
      G allele of rs1008438G>T may be a protective factor for cervical cancer among
      ethnic Han Chinese from Yunnan.

PMID- 29188630
TI  - [Application and modification of methods for chromosome culture, preparation and
      analysis].
AB  - Chromosome analysis has been widely used in clinics including prenatal diagnosis.
      To obtain high-quality metaphase chromosomes, researchers have attempted to
      modify the methods for chromosome culture, preparation and analysis. Some large
      research centers also tried to establish standards for quality control. In this
      paper, modification of methods for the preparation of chromosomes in the last
      decade is reviewed.

PMID- 29188631
TI  - [Advance in research on the correlation between genotypes of susceptible
      mutations and clinical phenotype of familial adenomatous polyposis].
AB  - Familial adenomatous polyposis (FAP) is one of the most common hereditary
      colorectal cancers. Its intestinal and extra-intestinal manifestations are
      correlated with mutation sties of the APC gene. Potential gene modulation sites
      in patients who have typical clinical manifestations but with unidentified APC
      mutations are also discussed, which included MUTYH gene, AXIN gene and certain
      epigenetic changes. With the generalization of Precision Medicine, to offer
      individualized treatment and surveillance strategy based on the genotype
      phenotype correlation will be of great value for FAP patients. This review
      focuses on the research advance in genotype - phenotype correlation studies of
      FAP patients.

PMID- 29188632
TI  - [Advance in clinical application of non-invasive prenatal screening using cell
      free fetal DNA].
AB  - Non-invasive prenatal screening using cell-free fetal DNA (NIPS) has been
      integrated into the prenatal health care only in a short span of five years, and
      the guidelines provided by professional bodies have been continuously updated.
      The American College of Medical Genetics and Genomics has made a statement on
      NIPS in July, 2016, suggesting that the NIPS can replace conventional screening
      for Patau, Edwards and Down syndromes in a continuum of gestational age and for
      any maternal age, except those who are significantly obese. The scope of target
      diseases of NIPS are also growing. Meanwhile, pre- and post-test counseling for
      NIPS has put forward a greater challenge for medical professionals.

PMID- 29188633
TI  - [Advance in molecular genetic research on X-linked syndromic hearing impairment].
AB  - In addition to hearing impairment, syndromic hearing impairment is often
      accompanied by disorders of urinary, skeletal, muscular, nervous, and ocular
      systems. Genetic factors have shown to play an important role in the pathogenesis
      of deafness. Mutations of X-linked genes may cause syndromic hearing impairment.
      Gene mapping, linkage analysis and next-generation sequencing may facilitate
      delineation of the pathogenesis of X-linked syndromic hearing impairment. This
      article reviews recent progress in molecular genetic research on X-linked
      syndromic hearing impairment, which may shed light for the diagnosis and
      treatment of these diseases.

PMID- 29188634
TI  - [A pedigree with dentatorubralpallidolyysian atrophy].

PMID- 29188635
TI  - [A pedigree with distal arthrogryposis].

PMID- 29188636
TI  - [Collaboration from periodontics in the aesthetic restoration of anterior teeth].
AB  - Anterior teeth are the main zones that reflect oral aesthetics. The histological
      structure, outside appearance, relative ratios, and other characteristics of
      tissues must be understood to obtain relatively ideal and natural restoration
      effects. A collaboration of different disciplines must be implemented to obtain
      harmonious and stable restoration outcomes that help the majority appreciate
      beauty. This article aims to discuss the role of periodontics in this
      collaboration and introduce several common techniques.

PMID- 29188637
TI  - [Treatment of complex crown-root fracture].
AB  - With the development of the oral clinical technology and materials, the concept
      of complex crown root fracture has become more scientific and developed.
      Epidemiological characteristics, causes and clinical features of this disease are
      generalized. Aesthetic, functional and minimally invasive coordination is
      reflected by expounding the diagnosis of complex crown-root fracture,
      recommendation of treatment and techniques, and characteristics of immature
      permanent teeth to systematize the treatment strategy, and to guide the clinical
      therapy of complex crown-root fracture.

PMID- 29188638
TI  - [Preparation processes of 3% yttria-stabilized tetragonal zirconia
      polycrystalline ceramic composite powders coated with nano-sized Al2O3-boron
      nitride].
AB  - OBJECTIVE: In this work, we aim to determine the optimum pH value for the
      preparation of 3% yttria-stabilized tetragonal zirconia polycrystalline (3Y
      TZP)/3%Al2O3 and optimum calcination temperature of Al2O3 precursor and amorphous
      boron nitride (BN) for Al2O3-BN coating 3Y-TZP powders. METHODS: The 3Y
      TZP/3%Al2O3 composite powders were prepared through the heterogeneous
      precipitation method under different pH values (6.5, 7.5, 8.5, and 9.5) and
      analyzed through transmission electron microscopy (TEM) to determine the optimum
      coating morphology. Al2O3 precursor, which was prepared under the optimum pH
      value, was calcined at different temperatures (800, 1 000, 1 200, and 1 400 C).
      The amorphous BN coating 3Y-TZP/3%Al2O3 powder was prepared via in situ reaction
      with boric acid and urea (calcined with N2 at 850 C for 5 and 3 h and 800 C for 5
      and 3 h). TEM, energy dispersive spectrometry (EDS), and X-ray diffraction (XRD)
      were performed to characterize the results. RESULTS: The optimum coating
      morphology was obtained at 8.5 pH. When the Al2O3 precursor was calcined at 1 200
      C and coated with BN (calcined with N2 at 800 C for 5 h), the Al-B-O compound was
      less, and t-ZrO2 was more represented. CONCLUSIONS: The optimum pH value for 3Y
      TZP/3%Al2O3 composite preparation is 8.5. For the preparation of Al2O3-BN coating
      3Y-TZP powders, the optimum calcination temperature of the Al2O3 precursor and
      amorphous BN are 1 200 and 800 C, respectively.

PMID- 29188639
TI  - [Construction of a eukaryotic expression vector of fibroblast activation protein
      and establishment of its stable over-expression in the oral squamous cell
      carcinoma].
AB  - OBJECTIVE: This study aimed at constructing fibroblast activation protein (FAP)
      over-expression lentivinus vectors to investigate transfection in SCC9 cell lines
      and establish a stable FAP over-expression oral squamous cell line. METHODS: The
      cDNA of FAP gene from an oral squamous cell carcinoma (OSCC) tissue was amplified
      by polymerase chain reaction (PCR) and subcloned into eukaryotic expression
      vector pCDH-CMV-MCS-EF1-copGFP. The recombinant plasmid was sequenced and then
      transfected into an SCC9 cell line. Subsequently, the SCC9 cell line that over
      expressed FAP stably was established by fluorescence activated cell sorting
      (FACS). The expression of green fluorescent protein (GFP) was detected with
      fluorescence microscopy, and the over-expression of FAP was identified by real
      time PCR and Western blot. RESULTS: The FAP gene was amplified by PCR and then
      cloned into the vector, whose sequence was identical to that in the GenBank. GFP
      was expressed in the transfected cells. Furthermore, FAP over-expression in the
      transfected cells was detected by real-time PCR and Western blot. CONCLUSIONS:
      The recombinant eukaryotic expression vector pCDH-FAP was constructed
      successfully. This result provides a foundation for further studies on the
      function of FAP in vitro.

PMID- 29188640
TI  - [Role of adenosine triphosphate-sensitive potassium channel in hydrogen sulfide
      induced inhibition of high glucoseinduced osteoblast damage].
AB  - OBJECTIVE: The aim of this study is to identify the role of adenosine
      triphosphate-sensitive potassium channel (KATP) in hydrogen sulfide (H2S)-induced
      inhibition of high glucose (HG)-induced osteoblast damage. METHODS: Osteoblasts
      from rat mandible were cultured and identified. The osteoblasts were then treated
      with HG, H2S, KATP channel opener pinacidil (Pia), and KATP channel blocker
      glibenclamide (Gli). Western blot method was performed to detect the expression
      of KATP channel protein. CCK8, reverse transcriptase polymerase chain reaction
      (RT-PCR) , and image analysis were used to determine the effects of H2S-KATP on
      the proliferation, differentiation, and mineralization of osteoblasts. RESULTS:
      The expression of KATP channel protein in osteoblasts was significantly decreased
      under the influence of HG. H2S pretreatment significantly inhibited HG on KATP
      channel protein down-regulation. Moreover, H2S pretreatment significantly
      inhibited the effect of HG on the proliferation of osteoblasts, thereby
      preventing HG-induced inhibition of osteoblasts differentiation and
      mineralization. Meanwhile, the KATP channel blocker effectively blocked the H2S
      on osteoblasts and had a protective effect. CONCLUSIONS: Through the KATP
      channel, H2S inhibited osteoblasts damage induced by HG.

PMID- 29188641
TI  - [Role of CCL5/CCR5 in the perineural invasion of salivary adenoid cystic
      carcinoma cells].
AB  - OBJECTIVE: This study aimed the role of the CCL5/CCR5 axis in the perineural
      invasion of salivary adenoid cystic carcinoma (SACC) cells. METHODS:
      Immunohistochemical analysis and flow cytometric analysis were conducted to
      detect the expression of the chemokine receptor CCR5 in SACC cells. Enzyme linked
      immunosorbent assay (ELISA) was performed to determine the expression of CCL5 in
      the supernate of human nerve cells. The flow cytometric analysis was applied to
      observe the changes in F-actin in SACC-LM cells, which were pretreated with CCL5.
      To assess the effects of the CCL5/CCR5 axis on the migration and invasion of SACC
      LM cells, we performed a scratch test and invasion assay under CCL5 stimulation.
      RESULTS: CCR5 was highly expressed in SACC cells. The concentration of CCL5 in
      the supernatant of human nerve cells was (359.2+/-15.8), (696.4+/-22.6) pg.mL-1.
      The CCL5/CCR5 axis promoted the migration and invasion of SACC-LM cells.
      CONCLUSIONS: The CCL5/CCR5 axis may be involved in the perineural invasion of
      SACC cells.

PMID- 29188642
TI  - [Evaluation for vertical stability after various orthognathic surgical treatment
      plans for skeletal class III malocclusion with anterior open-bite].
AB  - OBJECTIVE: To evaluate vertical stability after various orthognathic surgical
      treatment plans for skeletal class III malocclusion with anterior openbite.
      METHODS: A retrospective multicenter cohort study was conducted to investigate
      vertical stability after various orthognathic surgical treatment plans for
      skeletal class III malocclusion with anterior openbite. From 2010-2016, 122
      patients from two domestic stomatological hospitals were included in our study.
      Patients were divided into four groups according to their treatment plans,
      namely, bilateral sagittal split ramus osteotomy (BSSRO), intraoral vertical
      ramus osteotomy (IVRO), BSSRO+Le Fort I, and IVRO+Le Fort I. All patients
      followed a standardized examination procedure at 6 and 24 months post-treatment.
      The observation indexes include overbite, mandibular plane angle, and
      intermaxillary angle. RESULTS: 1) The significantly reduced ratio of the overbite
      in the BSSRO+Le Fort I and IVRO+Le Fort I groups were less than the BSSRO and
      IVRO groups at 6 and 24 months post-treatment. 2) The significantly increased
      ratio of the mandibular plane in BSSRO+Le Fort I and IVRO+Le Fort I groups were
      less than BSSRO and IVRO groups at 6 and 24 months post-treatment. 3) The
      significantly increased ratio of the intermaxillary angles in BSSRO+Le Fort I and
      IVRO+Le Fort I groups were less than the BSSRO and IVRO groups at 6 months post
      treatment, while there was no statistical difference at 24 months post-treatment.
      CONCLUSIONS: Bimaxillary surgery (BSSRO+Le Fort I and IVRO+Le Fort I) is more
      effective than mandibular surgery to control vertical relapse.

PMID- 29188643
TI  - [Effect of body image in adolescent orthodontic treatment].
AB  - OBJECTIVE: This study was designed to probe the psychological factors adolescent
      orthodontic patients, the role of body image and self-esteem in the whole process
      of orthodontic treatment and the impact on the efficacy and satisfaction of
      orthodontic. METHODS: Five hundred and twenty-eight patients were selected in
      this study. The Aesthetic Component of the Index of Orthodontic Treatment Need
      (IOTN-AC) , Rosenberg Self-Esteem Scale (SES), Negative Physical Self-General
      (NPS-G) and other body analysis scale study after orthodontic lasted 18-24 months
      were used to investigate the role of body image in adolescent orthodontic
      treatment. RESULTS: Esthetic evaluation of patients teeth after correction had
      been significantly improved, patient self-evaluation difference IOTN-AC doctor
      evaluation, Psychosocial Impact of Dental Aesthetics Questionnaire-tooth
      confidence, aesthetic concerns, psychological impact and social function were
      significantly improved. The improvement of the dental aesthetics component (T2
      when doctors evaluate IOTN-AC) was positively correlated with the evaluation of
      the efficacy, and was significantly negatively correlated with the negative
      emotions of patients at baseline. CONCLUSIONS: Negative body image-dental
      dissatisfied-cognitive component and the affective component, the overall
      negative body image and negative emotions can predict patient satisfaction with
      treatment efficacy. Orthodontic treatment not only improves the self-aesthetic
      evaluation of adolescent patients, but also has a positive effect on the mental
      health of adolescent patients.

PMID- 29188644
TI  - [Study on using laser Doppler flowmetry to determine the pulpal blood flow of
      immature maxillary incisors].
AB  - OBJECTIVE: This study aimed to evaluate the influence of age on the pulpal blood
      flow (PBF) of immature maxillary incisors of maxillary incisors, which was
      detected by laser Doppler flowmetry (LDF). METHODS: LDF was used to detect the
      PBF value of maxillary central and lateral incisors of a child group (aged 7-13
      years old) and a positive control group (aged 18-25 years old), as well as the
      central incisor of a negative control group (the central incisor had undergone
      endodontic treatment). We then compared the features of PBF in all groups with
      the influence of gender and position on PBF. The relation of maxillary central
      incisor and lateral incisor, age, and maxillary incisor were analyzed. RESULTS:
      The PBF value of the negative control group was (2.08+/-0.73) PU. The PBF values
      in the positive control group in central and lateral incisors were (8.49+/-1.88)
      and (7.52+/-1.82) PU. In the child group, PBF values in central incisors and
      lateral incisors were (11.31+/-2.21) and (12.18+/-2.65) PU. A significant
      difference was observed between different groups and between central and lateral
      incisors (P<0.01). Meanwhile, no significant difference was found in the PBF
      values between the right and the left parts in both males and females (P>0.05).
      Age had a linearity negative correlation with the PBF value of incisors in the
      child group. A linear negative correlation existed between the age and PBF of
      central and lateral incisors (r=-0.310 and r=-0.510, respectively) (P<?0.01).
      CONCLUSIONS: PBF value decreased with increased age in children aged 7-13 years
      old.

PMID- 29188645
TI  - [Effect of osseointegration in the posterior area by Shenggu pills].
AB  - OBJECTIVE: This study aimed to investigate the osseointegration condition by
      measuring the implant stability quotient (ISQ) to study the effect of
      osseointegration in the posterior area by Shenggu pills. METHODS: A total of 101
      DENTIUM implants were placed in 48 patients. Fifty implants placed in 24 patients
      were addressed as usual, whereas 51 implants placed in 24 patients were treated
      with Shenggu pills. ISQ was tested on the day of surgery and consecutively at 4,
      8, and 12 weeks. All data were analyzed. RESULTS: The efficacy of the treatment
      group was no much better than that of control group on the day of surgery and
      consecutively at 12 weeks with no significant difference (P>0.05). The efficacy
      of the treatment group was significantly better than that of the control group at
      4 and 8 weeks (P<0.05). The implants placed in the mandible were significantly
      better than those placed in the maxilla (P<0.05). CONCLUSIONS: Early intake of
      Shenggu pills could accelerate the implant bone union, improve the implants' ISQ,
      and ensure the success rate of the operation.

PMID- 29188646
TI  - [Application of temporomandibular joint dics reduction in the operation of
      condylar sagittal fracture].
AB  - OBJECTIVE: To explore the selection of temporomandibular joint (TMJ) disc
      reduction and fixation methods in condylar sagittal fracture surgery. METHODS: A
      total of 36 patients with condylar fractures were chosen. The follow-up period
      was more 6 months. All 36 cases of condylar sagittal fracture were fixed with
      long screw. In the operation, the displaced joint disc was repositioned and
      fixed. The fixed method included direct suture (22 cases) and anchorage (14
      cases). Clinical followups were performed before surgery and 1 month, 3 months, 6
      months and 1 year after surgery. Clinicians recorded data related to the Fricton
      craniomandibular index (CMI) and evaluated the postoperative joint function
      during followup before surgery and 6 months after surgery. RESULTS: In both
      groups, function of TMJ significantly improved after surgery. The CMI decreased
      from 0.213+/-0.162 and 0.273+/-0.154 to 0.059+/-0.072 and 0.064+/-0.068 (P<0.05),
      respectively. No statistical difference was observed between the two groups in
      palpation index (PI), dysfunction index (DI) and CMI (P>0.05) before or after
      surgery. CONCLUSIONS: Both methods could effectively improve the dysfunction of
      the TMJ caused by trauma. The selection of joint disc reduction and fixation
      methods is based on the displacement and damage degree of the joint disc.

PMID- 29188647
TI  - [Experimental study on accelerated healing of jaw fracture using gelatin sponge
      compound growth factor].
AB  - OBJECTIVE: To explore the role and mechanism of drug delivery systems using
      growth factor combined with gelatin sponge on accelerating the healing of jaw
      fracture and to seek better treatment of accelerating the maxillofacial fracture.
      METHODS: About 100 MUg recombinant human bone morphogenetic protein (BMP)-2 was
      completely dissolved in 1 mL recombinant bovine basic fibroblast growth factor
      (bFGF), and the solution (40 MUL) was dropped in gelatin sponge (0.5 cm*0.5
      cm*1.0 cm). Then, it was freeze dried and prepared into bFGF/BMP/gelatin sponge
      delivery systems. The mandibular fracture model on two sides were prepared in 12
      New Zealand rabbits and randomly divided into two groups. The left side was the
      control group, which was only fixed with titanium plates. The right side was the
      experimental group, in which bFGF/BMP/gelatin sponge delivery systems were put
      under the titanium plates. General observation, X-ray, and histological
      examination were taken at 2, 4, and 12 weeks after surgery. RESULTS: After 2
      weeks, more fibrous tissues were seen between the fracture ends in the
      experimental group than in the control group. After 4 weeks, fibrous fracture
      callus were seen in the fracture gap in the experimental group. The ingrowths of
      fibrous tissue and blood vessels were seen in the control group. The fracture
      healing of the experimental group was significantly faster than the control group
      at 2 and 4 weeks. After 12 weeks, the experimental and control groups all healed
      completely. CONCLUSIONS: bFGF/BMP/gelatin sponge can accelerate and improve
      fracture healing; thus, it has better clinical application prospect.

PMID- 29188648
TI  - [Application of bone grafts from chin of the mandible in the reconstruction of
      orbital fracture].
AB  - OBJECTIVE: To evaluate the clinical effects of bone graft from the mandible in
      repairing orbital floor defects. METHODS: Bone grafts from the mandible were used
      to treat 11 cases of orbital floor defects and followed up for 6-12 months.
      RESULTS: The surgical incisions healed primarily in all 11 patients. The orbital
      floor structure was restored. No vision loss, limited eye movement, implant
      infection, or resorption were observed postoperatively, and no complications
      occurred in the supply area. CONCLUSIONS: Bone grafts from the mandible were an
      ideal material to repair orbital floor defects.

PMID- 29188649
TI  - [Correlation between interleukin-10 polymorphisms and susceptibility to chronic
      periodontitis among Uygur adults in the Moyu area].
AB  - OBJECTIVE: This study aims to investigate the association between interleukin
      (IL)-10-597 (C/A) single-nucleotide polymorphisms and chronic periodontitis of
      Moyu Uygur population in Xinjiang Uygur Autonomous Region of China. METHODS: In
      accordance with the inclusion and exclusion criteria, the buccal swabs of 300
      subjects were randomly selected from the epidemiological investigation of Uygur
      adults in Moyu county on April and May 2013. The study was conducted on a healthy
      control group, a mild chronic periodontitis group, and a moderate-to-severe
      chronic periodontitis group, with each comprising 100 samples. The IL-10-597(C/A)
      site in the promoter sequences was analyzed using the tetra-primer amplification
      refractory mutation system-polymerase chain reaction method to test the genotype
      and allele distributions. Statistical analysis was performed using Chi-squared
      test and ordinal classification Logistic regression analysis. RESULTS: The
      genotype and allele frequencies of the IL-10-597(C/A) site in the healthy control
      group, mild chronic periodontitis group, and moderate-to-severe chronic
      periodontitis group exhibited no significant difference (P>0.05). The age of all
      the samples was associated with chronic periodontitis. The risk of chronic
      periodontitis in the people of 55-65 years old was 25 times in the people under
      the age of 35 (OR=25.56, P<0.001). CONCLUSIONS: The IL-10-597 (C/A) single
      nucleotide polymorphisms in the gene promoter are not associated with chronic
      periodontitis in Uygur adult population.

PMID- 29188650
TI  - [The role of extracellular signal regulated kinase 1/2 in mediating
      osteodifferentiation of human periodontal ligament cells induced by cyclic
      stretch].
AB  - OBJECTIVE: This study aimed to investigate the mechanism of cyclic stretch that
      promotesthe osteogenic differentiation of human periodontal ligament cells
      (hPDLCs) through the mediation of extracellular-signal-regulated kinase 1/2
      (ERK1/2). METHODS: hPDLCs were isolated through the explant method and cultured
      in vitro. hPDLCs were mechanically stimulated by a multi-channel cell-stress
      loading system for 1, 3, 6, 12, and 24 h. The magnitude of stretch was 10%
      deformation, and the frequency was 0.5 Hz. Nonloaded cells were used as control
      group. ERK1/2 activation was blocked by U0126, a specific ERK1/2 pathway
      inhibitor. Additionally, hPDLCs were transfected with adenoviral vector encoding
      dominant negative ERK1/2 (DN-ERK1/2) to continuouslyinhibit ERK1/2 activation.
      The mRNA and protein levels of target geneswere detected through real-time
      polymerase chain reaction and Western blot. RESULTS: Cyclic stretching promoted
      the expression of ERK1/2, osteocalcin (OCN) mRNA, and bone sialoprotein (BSP)
      mRNA. The expression of runt-related transcription factor (Runx) 2 protein and
      mRNA also increased at 3 and 6 h of cyclic stretching. The inhibition of ERK1/2
      by U0126 and DN-ERK1/2 suppressed the expressionof Runx2 mRNA, OCN mRNA, BSP
      mRNA, Runx 2 protein, and p-ERK1/2 protein relative to that in stretched cells
      without the ERK1/2 inhibitor. CONCLUSIONS: ERK1/2 is a critical molecule in the
      mediation ofthe osteogenic differentiation of hPDLCs under mechanical
      stimulation. ERK1/2 activation induced the elevation of Runx2 protein levels,
      which may be involved in the stretch-induced expressions of OCN and BSP.

PMID- 29188651
TI  - [Research progress on the relationship and mechanisms between periodontal disease
      and preterm birth and low-birth-weight infants].
AB  - Preterm birth (PB) is defined as the birth of a baby less than 37 weeks of
      gestational age. Low birth weight (LBW) is defined as a newborn baby's weight of
      less than 2 500 g. PB is often accompanied by LBW. Preterm low birth weight
      (PLBW) is the leading cause of newborn deaths. Periodontal disease (PD) is a
      chronic oral infectious disease, and it is closely related with general health.
      Epidemiological data show that PD is a risk factor for PLBW and other adverse
      pregnancy outcomes. The possible mechanisms include the direct effects of
      periodontal bacteria, inflammatory reactions, and immune response; however, the
      exact pathogenetic mechanism involved remains controversial. This article aims to
      review the research progress on the relationship between PD and PLBW and their
      underlying mechanisms, as well as the effects of periodontal treatment on PLBW
      incidence.

PMID- 29188652
TI  - [Clinical applications of stem cells from human exfoliated deciduous teeth in
      stem cell therapy].
AB  - Stem cells from human exfoliated deciduous teeth (SHED) are one category of
      dental stem cells. They belong to ectodermal mesenchymal stem cells. As an ideal
      stem cell source, SHED possess great potential in stem cell therapy. This review
      demonstrates the biological characteristics and advantages of SHED in stem cell
      therapy and discusses its multiple functions in tissue regeneration and repair,
      including multiple differentiation potentiality, cell secretion of cytokines, and
      immunomodulatory ability. Furthermore, this article introduces the main findings
      regarding the potential clinical applications of SHED to a variety of diseases.
      This article demonstrates research progress in dentin-pulp regeneration,
      maxillofacial bone regeneration, and treatment of nervous system and immune
      system diseases with SHED for stem cell transplantation.

PMID- 29188653
TI  - [Research progress on the type IX secretion system of Porphyromonas gingivalis].
AB  - In recent years, the study found that Porphyromonas gingivalis type IX secretion
      system (T9SS) is a novel protein secretion system, also known as Por secretion
      system (PorSS). Unlike the eight protein secretion systems found in the past, the
      system is a polyprotein complex found only in Bacteroides. The secreted proteins
      have both N- and C-terminus, where the former includes Sec-dependent type I
      signals peptide, and the latter contains conserved domains (C-terminal conserved
      domain, CTD). Porphyromonas gingivalis T9SS includes proteins such as intima,
      outer membrane, cytoplasm, and cell cycle, including at least 34 proteins
      containing CTD. Porphyromonas gingivalis T9SS is involved in regulating
      associated virulence factors including gingivin, fimbriae, lipopolysaccharide,
      HBP35, CPG70 protein and peptidyl-arginine deiminase. These CTD-containing
      virulence proteins are localized by T9SS and then released to the extracellular
      domain, thereby destroying periodontal tissue. Therefore, this review summarizes
      the research progress on the T9SS of Porphyromonas gingivalis.

PMID- 29188654
TI  - [Research progress on QMix properties in root canal irrigation].
AB  - Mechanical instrumentation preparation alone is insufficient to completely remove
      root canal infection, and chemical irrigation is essential to eliminate infected
      remnants. An ideal root canal irrigant should completely remove the smear layer,
      lubricate the root canal, efficiently kill bacteria, induce mild or no
      inflammatory response in the tissues, and avoid damaging the dentin structure.
      However, a commercial irrigant that meets all these requirements is currently
      lacking. QMix is a root canal irrigation mixture of ethylenediamine tetraacetic
      acid (EDTA), chlorhexidine (CHX) and surfactant. This mixture can remove the
      smear layer efficiently, and it possesses strong antibacterial effect and good
      biocompatibility with minimal cytotoxicity. Furthermore, the influence of QMix on
      the color and micro-hardness of dentin is low, and it can improve the wettability
      of root canal sealant without affecting its adhesive properties. This review
      compares the efficiencies of QMix with other irrigants (sodium hypochlorite, CHX,
      EDTA, SmearClear, and MTAD) in term of smear layer removal, dentine and root
      canal sealing, cell cytotoxicity, and bacterial growth inhibition.

PMID- 29188655
TI  - [Taste signal transduction and the role of taste receptors in the regulation of
      microbial infection].
AB  - Taste receptors guide individuals to consume nutrients while avoiding potentially
      noxious substances. Interestingly, recent studies have shown that taste receptors
      are also expressed beyond the taste buds, including brain, respiratory system,
      and digestive system, etc. These extragustatory taste receptors play important
      roles in microbial infection, nutrient uptake and host homeostasis. Mang
      extragustatory taste receptors have been proposed to sense microorganisms and
      regulate host innate defense. More importantly, polymorphisms of genes encoding
      taste receptor, particularly bitter taste receptor, are linked to different
      innate defensive responses. This review introduces the molecular basis of taste
      signal transduction, and the role of taste receptors in the regulation of innate
      immunity during microbial infection were further discussed in detail.

PMID- 29188656
TI  - [Features of condylography curves].
AB  - With the kinematic face bow, the condyle movements representing temporomandibular
      joint function can be recorded instantly. The condylography curves can be
      utilized for diagnostic analysis, as different pathophysiological conditions have
      unique curve patterns. By tracing the specific alterations on the curves, the
      structural and functional statuses of the temporomandibular joint can be
      predicted. However, to the best of our knowledge, no standardized and practicable
      evaluation protocol for jaw movement tracing exists. In the current study, the
      features of either normal or abnormal curves were reviewed. Such features can be
      clinically used for determining temporomandibular joint status, thereby
      contributing to a comprehensive diagnosis.

PMID- 29188657
TI  - [Synchronous carcinoma of the floor of mouth carcinoma with esophageal carcinoma:
      a case report].
AB  - This study presents a case of synchronous multiple primary cancers involving
      floor of mouth carcinoma with esophageal carcinoma. Literature was reviewed to
      summarize the incidence, location, diagnosis, treatment characteristics, and
      prognosis to improve understanding and awareness of the multiple primary cancer.
      As a result, early discovery, early diagnosis, and effective treatment can help
      prolong survival and improve the quality of life of patients.

PMID- 29188658
TI  - Assessing local stromal alterations in human ovarian cancer subtypes via second
      harmonic generation microscopy and analysis.
AB  - The collagen architecture in all human ovarian cancers is substantially
      remodeled, where these alterations are manifested in different fiber widths,
      fiber patterns, and fibril size and packing. Second harmonic generation (SHG)
      microscopy has differentiated normal tissues from high-grade serous (HGS) tumors
      with high accuracy; however, the classification between low-grade serous,
      endometrioid, and benign tumors was less successful. We postulate this is due to
      known higher genetic variation in these tissues relative to HGS tumors, which are
      genetically similar, and this results in more heterogeneous collagen remodeling
      in the respective matrix. Here, we examine fiber widths and SHG emission
      intensity and directionality locally within images (e.g., 10*10  microns) and
      show that normal tissues and HGS tumors are more uniform in fiber properties as
      well as in fibril size and packing than the other tissues. Moreover, these
      distributions are in good agreement with phase matching considerations relating
      SHG emission directionality and intensity. The findings show that in addition to
      average collagen assembly properties the intrinsic heterogeneity must also be
      considered as another aspect of characterization. These local analyses showed
      differences not shown in pure intensity-based image analyses and may provide
      further insight into disease etiology of the different tumor subtypes.

PMID- 29188659
TI  - Morphometric analysis of erythrocytes from patients with thalassemia using
      tomographic diffractive microscopy.
AB  - Complete blood count is the most common test to detect anemia, but it is unable
      to obtain the abnormal shape of erythrocytes, which highly correlates with the
      hematologic function. Tomographic diffractive microscopy (TDM) is an emerging
      technique capable of quantifying three-dimensional (3-D) refractive index (RI)
      distributions of erythrocytes without labeling. TDM was used to characterize
      optical and morphological properties of 172 erythrocytes from healthy volunteers
      and 419 erythrocytes from thalassemic patients. To efficiently extract and
      analyze the properties of erythrocytes, we developed an adaptive region-growing
      method for automatically delineating erythrocytes from 3-D RI maps. The
      thalassemic erythrocytes not only contained lower hemoglobin content but also
      showed doughnut shape and significantly lower volume, surface area, effective
      radius, and average thickness. A multi-indices prediction model achieved perfect
      accuracy of diagnosing thalassemia using four features, including the optical
      volume, surface-area-to-volume ratio, sphericity index, and surface area. The
      results demonstrate the ability of TDM to provide quantitative, hematologic
      measurements and to assess morphological features of erythrocytes to distinguish
      healthy and thalassemic erythrocytes.

PMID- 29188661
TI  - Automatic classification of retinal three-dimensional optical coherence
      tomography images using principal component analysis network with composite
      kernels.
AB  - We present an automatic method, termed as the principal component analysis
      network with composite kernel (PCANet-CK), for the classification of three
      dimensional (3-D) retinal optical coherence tomography (OCT) images.
      Specifically, the proposed PCANet-CK method first utilizes the PCANet to
      automatically learn features from each B-scan of the 3-D retinal OCT images.
      Then, multiple kernels are separately applied to a set of very important features
      of the B-scans and these kernels are fused together, which can jointly exploit
      the correlations among features of the 3-D OCT images. Finally, the fused
      (composite) kernel is incorporated into an extreme learning machine for the OCT
      image classification. We tested our proposed algorithm on two real 3-D spectral
      domain OCT (SD-OCT) datasets (of normal subjects and subjects with the macular
      edema and age-related macular degeneration), which demonstrated its
      effectiveness.

PMID- 29188660
TI  - Multiphoton fluorescence lifetime imaging of chemotherapy distribution in solid
      tumors.
AB  - Doxorubicin is a commonly used chemotherapeutic employed to treat multiple human
      cancers, including numerous sarcomas and carcinomas. Furthermore, doxorubicin
      possesses strong fluorescent properties that make it an ideal reagent for
      modeling drug delivery by examining its distribution in cells and tissues.
      However, while doxorubicin fluorescence and lifetime have been imaged in live
      tissue, its behavior in archival samples that frequently result from drug and
      treatment studies in human and animal patients, and murine models of human
      cancer, has to date been largely unexplored. Here, we demonstrate imaging of
      doxorubicin intensity and lifetimes in archival formalin-fixed paraffin-embedded
      sections from mouse models of human cancer with multiphoton excitation and
      multiphoton fluorescence lifetime imaging microscopy (FLIM). Multiphoton
      excitation imaging reveals robust doxorubicin emission in tissue sections and
      captures spatial heterogeneity in cells and tissues. However, quantifying the
      amount of doxorubicin signal in distinct cell compartments, particularly the
      nucleus, often remains challenging due to strong signals in multiple
      compartments. The addition of FLIM analysis to display the spatial distribution
      of excited state lifetimes clearly distinguishes between signals in distinct
      compartments such as the cell nuclei versus cytoplasm and allows for
      quantification of doxorubicin signal in each compartment. Furthermore, we
      observed a shift in lifetime values in the nuclei of transformed cells versus
      nontransformed cells, suggesting a possible diagnostic role for doxorubicin
      lifetime imaging to distinguish normal versus transformed cells. Thus, data here
      demonstrate that multiphoton FLIM is a highly sensitive platform for imaging
      doxorubicin distribution in normal and diseased archival tissues.

PMID- 29188662
TI  - [Analysis of Differentially Expressed Proteins Distribution in the Rat Brains
      with DAI by MALDI-TOF-IMS].
AB  - OBJECTIVES: To establish the imaging mass spectrometry for analysis of
      differentially expressed proteins distribution in the rat brains with diffuse
      axonal injury (DAI) based on matrix assisted laser desorption/ionization-time of
      flight imaging mass spectrometry (MALDI-TOF-IMS). METHODS: MALDI-TOF-IMS scanning
      were conducted on the brains of DAI group and control group in the m/z range of 1
      000 to 20 000 using AutoflexIII MALDI-TOF spectrometer. ClinProTool 2.2 software
      was used for statistical analysis on the data of two groups, and then the
      differentially expressed proteins were picked out to conduct imaging. The
      distribution of the proteins with different m/z in the rat brains was observed.
      RESULTS: Five proteins with different m/z, including 4 963, 5 634, 6 253, 6 714
      and 7 532, differentially expressed in the rat brains with DAI. CONCLUSIONS:
      MALDI-TOF-IMS can be used for studying the differentially expressed proteins in
      rat brains with DAI and the analysis method is established for exploring the
      distribution of differentially expressed proteins in the rat brains with DAI
      using imaging mass spectrometry.

PMID- 29188663
TI  - [Correlation between RNA Expression Level and Early PMI in Human Brain Tissue].
AB  - OBJECTIVES: To explore the correlation between the expression levels of several
      RNA markers in human brain tissue and early postmortem interval (PMI). METHODS:
      Twelve individuals with known PMI (range from 4.3 to 22.5 h) were selected and
      total RNA was extracted from brain tissue. Eight commonly used RNA markers were
      chosen including beta-actin, GAPDH, RPS29, 18S rRNA, 5S rRNA, U6 snRNA, miRNA-9
      and miRNA-125b, and the expression levels were detected in brain tissue by real
      time fluorescent quantitative PCR. The internal reference markers with stable
      expression in early PMI were screened using geNorm software and the relationship
      between its expression level and some relevant factors such as age, gender and
      cause of death were analyzed. RNA markers normalized by internal reference were
      inserted into the mathematic model established by previous research for PMI
      estimation using R software. Model quality was judged by the error rate
      calculated with estimated PMI. RESULTS: 5S rRNA, miRNA-9 and miRNA-125b showed
      quite stable expression and their expression levels had no relation with age,
      gender and cause of death. The error rate of estimated PMI using beta-actin was
      24.6%, while GAPDH was 41.0%. CONCLUSIONS: 5S rRNA, miRNA-9 and miRNA-125b are
      suitable as internal reference markers of human brain tissue owing to their
      stable expression in early PMI. The expression level of beta-actin correlates
      well with PMI, which can be used as an additional index for early PMI estimation.

PMID- 29188664
TI  - [Comparative Study on Morphology of Human, Swine, Sheep and Cattle Muscle Tissues
      and Its Forensic Significance].
AB  - OBJECTIVES: To observe the morphological characteristic indexes of the muscle
      tissues from different species and to establish a discriminant equation of
      species identification and tried to establish a new method for species
      identification. METHODS: Three different parts of the muscle tissues, triceps
      brachii, biceps femoris and erector spinae from adult human corpses, triceps
      brachii, biceps femoris and longissimus dorsi muscle from swine, sheep and cattle
      reached the slaughter age, were extracted respectively (20 for each group) and
      deal the tissues into paraffin sections. Eleven observational indexes of the
      muscle tissues from adult human corpses, swine, sheep and cattle were detected.
      Statistical methods were used to analyze the data and a discriminant equation of
      species identification was established. RESULTS: Four observation indicators were
      screened for establishing the discriminant equation of species identification
      among human, swine, sheep and cattle. The accurate rate of this method for human
      muscle tissue identification was 90%, and for swine, sheep, and cattle muscle
      tissue were 80%, 100% and 80% respectively. CONCLUSIONS: The morphological method
      provides a new method for the species identification of the muscle tissue among
      human, swine, sheep and cattle, and it can be used as a reference for the
      identification of animal species.

PMID- 29188665
TI  - [Identification of Vaginal Fluid Using Microbial Signatures].
AB  - OBJECTIVES: To investigate the specific microbial signatures in vaginal fluid.
      METHODS: Vaginal fluid (16 samples), saliva (16 samples), feces (16 samples),
      semen (8 samples), peripheral blood (8 samples), urine (5 samples), and nasal
      secretion (4 samples) were collected respectively. The 16S rRNA genes of
      Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii,
      Lactobacillus iners, and Atopobium vaginae were amplified. PCR production was
      detected via a 3130xl Genetic Analyzer. RESULTS: The detected number of
      Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii,
      Lactobacillus iners, and Atopobium vaginae were 15, 5, 8, 14, and 3 in all
      vaginal fluid samples, respectively. Lactobacillus crispatus and Lactobacillus
      jensenii existed specifically in vaginal fluid. CONCLUSIONS: There is a potential
      application value to detect Lactobacillus crispatus and Lactobacillus jensenii
      for the identification of vaginal fluid.

PMID- 29188666
TI  - [Genetic Polymorphisms of SNP Located in the 5' Region of VEGF Gene in Han
      Population in Guangdong].
AB  - OBJECTIVES: To investigate the genetic polymorphism of SNP located in the 5'
      region of the vascular endothelial growth factor (VEGF) gene in Han population in
      Guangdong and provide basic data for forensic application and population genetics
      research. METHODS: The genetic polymorphisms of 4 SNP loci (rs699947, rs1570360,
      rs833061, rs2010963) within 5' region of VEGF gene of 184 unrelated individuals
      in Han population in Guangdong were analyzed by DNA micro sequencing technology
      SNaPshot. The statistical analysis was carried out by PowerMarker v3.25 software.
      RESULTS: The genotype distributions of the 4 SNP loci within 5' region of VEGF
      gene of 184 unrelated individuals in Han population in Guangdong were in
      accordance with Hardy-Weinberg equilibrium (P>0.05) and 3 kinds of genotypes were
      detected from each loci. There was high linkage disequilibrium between the
      rs833061 and rs699947 SNP loci. Six haplotypes were observed, while the frequency
      of C-G-T-C, C-G-T-G, A-A-C-G and A-G-C-G were more than 10%, which were the main
      haplotypes. The discrimination probabilities (DP) of rs699947, rs833061, and
      rs2010963 loci were between 0.583 and 0.634, with the power of exclusion (PE)
      between 0.133 and 0.144. The DP and PE of haplotypes of 4 SNP were 0.868 and
      0.438, respectively. CONCLUSIONS: There are great polymorphisms in the 5' region
      of VEGF gene in Han population in Guangdong, which could be used as genetic
      indexes for individual identification and paternity testing, as well as
      association analysis of the related diseases.

PMID- 29188667
TI  - [Simultaneous Determination of Three Kinds of Effective Constituents in Cannabis
      Plants by Reversed-phase HPLC].
AB  - OBJECTIVES: To establish a high performance liquid chromatographic (HPLC) method
      for simultaneous determination of three effective constituents, including
      tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in Cannabis
      plants. METHODS: A C18 column was used in this study, and acetonitrile-phosphate
      buffer (0.015 mol/L KH2PO4) was used as mobile phase at a flow rate of 1.0
      mL/min. At a detection wavelength of 220 mm, UV absorption spectra were collected
      at the wavelength range of 190-400 nm, and the spectra and retention time were
      counted as qualitative evidence. RESULTS: THC, CBD and CBN could be well
      separated by this method. Three components had good linear relationship in the
      range of 0.4-40 MUg/mL (R2>=0.999 3). The recoveries were over 87%. The limits of
      detection were 1.8 ng, 2.0 ng and 1.3 ng, respectively. The relative standard
      deviation (RSD) were less than 5% for both inter-day and intra-day precisions.
      CONCLUSIONS: Reversed-phase HPLC method is simple, rapid and accurate, and it is
      suitable for the qualitative and quantitative detection of THC, CBD and CBN in
      Cannabis plants.

PMID- 29188668
TI  - [Analysis of Forensic Characteristics about 23 Family Homicide Cases].
AB  - OBJECTIVES: To provide references for forensic analysis of family homicides cases
      by analyzing the situations of scene, injuries and individual which were related
      to the family homicide cases in a county. METHODS: The data of 23 family homicide
      cases from 2004 to 2013 were collected. The basic situation of individual
      involved, the relationship between dead and suspect, the cause of death, the
      motive, the location, time and tools of the crime and the behavior of the suspect
      after crime etc. were analyzed. RESULTS: The characteristics of the 23 family
      homicides cases showed that couple relationship was the most common relationship;
      passion killing was the most common motive; local materials were mostly used as
      the tools for committing crimes; most crimes were committed in residences; most
      time of crime was night. CONCLUSIONS: The analysis of family homicide cases
      should be based on the scene investigation, the examination of the body and
      combined with the investigation of the situation.

PMID- 29188669
TI  - [Forensic Analysis of 20 Dead Cases Related to Heroin Abuse].
AB  - OBJECTIVES: To perform retrospective analysis on 20 dead cases related to heroin
      abuse, and to provide references for the forensic assessment of correlative
      cases. METHODS: Among 20 dead cases related to heroin abuse, general situation,
      using method of drug, cause of death and result of forensic examination were
      analyzed by statistical analysis for summarizing the cause of death and
      pathologic changes. RESULTS: The dead were mostly young adults, with more male
      than female. The results of histopathological examinations showed non-specific
      pathological changes. There were four leading causes of death, including acute
      poisoning of heroin abuse or leakage (13 cases, 65%), concurrent diseases caused
      by heroin abuse (3 cases, 15%), inspiratory asphyxia caused by taking heroin (2
      cases, 10%), and heroin withdrawal syndrome (2 cases, 10%). CONCLUSIONS: The
      forensic identification on dead related to heroin abuse must base on the
      comprehensive autopsy, and combine with the qualitative and quantitative analysis
      of heroin and its metabolites in death and the case information, as well as the
      scene investigation.

PMID- 29188670
TI  - [Genetic Polymorphisms of 24 Y-STR Loci in Nanjing Han Population].
AB  - OBJECTIVES: To investigate the genetic polymorphism of DYS391 and other 23 Y-STR
      loci and to explore its application value in forensic science. METHODS: Y-STRs
      loci of 580 unrelated Han males in Nanjing were amplified using AGCU Y-PLUS PCR
      (24) kit. The genetic parameters of 24 Y-STR loci such as gene frequency were
      calculated by software, and compared with the data of Hubei, Liao- ning,
      Guangdong, Beijing and Chengdu Han population. RESULTS: Total 580 haplotypes were
      detected among 24 Y-STR loci in 580 unrelated Han males in Nanjing. The genetic
      diversity (GD) of each locus was from 0.294 6 to 0.939 8, and the haplotypes
      diversity (HD) was 0.983 7. There was a significant difference between the GD of
      6 areas. CONCLUSIONS: The 24 Y-STR loci such as DYS391 in Nanjing Han population
      have an application value in forensic science. They can also be used for cases
      testing and pedigree investigation.

PMID- 29188671
TI  - [Application of Postmortem Biochemistry in Forensic Diagnosis of Diabetic
      Ketoacidosis].
AB  - Diabetic ketoacidosis is a serious complication results from the high blood
      levels of glucose and ketone in diabetes mellitus patients that cause metabolic
      overbalance. An analysis of postmortem biochemical indexes is needed in such
      cases without specific signs of the routine forensic medicine examination.
      Postmortem biochemistry is a kind of examinations that collecting the body fluids
      of the corpses to determine the metabolic state of their life time to estimate
      the cause of death. This paper reviews the basic features and signs of the
      forensic medicine examination in the dead cases of diabetic ketoacidosis, and
      emphatically analyzes the postmortem biochemical indexes of diabetic
      ketoacidosis, and summarizes new ideas of forensic medicine diagnosis in diabetic
      ketoacidosis death.

PMID- 29188672
TI  - [Progress on the Rule of Clavicle Epiphyseal Closure Using Multi-Imaging
      Technology].
AB  - People aged 18 years could be punished lightly or diminished criminal
      responsibility, even be spared the death sentence, which has important meaning in
      Chinese judicatory adjudication. The epiphysis of long bones from human limbs and
      the secondary sexual characteristics almost have developed completely before 18
      years old. Clavicle epiphysis is one of the articular metaphysis which has a late
      epiphyseal closure. The recent studies in exploring the rule of clavicle
      epiphyseal by multi-imaging technology shows that the development of clavicle
      epiphysis has some value in age estimation of 18 years old. CT, especially thin
      section CT, is widely used at present. However, thin-section CT scanning has
      great net radiation, which is not ethically acceptable if it is not for diagnosis
      and treatment. MRI is nonradioactive tomographic imaging and easy to evaluate,
      which is one of the future research directions in forensic age estimation using
      the medial clavicle. This paper summarizes the progress on the rule of clavicle
      epiphyseal closure, and analyzes and summarizes the feasibility of rule of
      clavicle epiphyseal closure applies on age estimation.

PMID- 29188673
TI  - [Review of Second Generation Sequencing and Its Application in Forensic
      Genetics].
AB  - The rapid development of second generation sequencing (SGS) within the past few
      years has led to the increasement of data throughput and read length while at the
      same time brought down substantially the sequencing cost. This made new
      breakthrough in the area of biology and ushered the forensic genetics into a new
      era. Based on the history of sequencing application in forensic genetics, this
      paper reviews the importance of sequencing technologies for genetic marker
      detection. The application status and potential of SGS in forensic genetics are
      discussed based on the already explored SGS platforms of Roche, Illumina and Life
      Technologies. With these platforms, DNA markers (SNP, STR), RNA markers (mRNA,
      microRNA) and whole mtDNA can be sequenced. However, development and validation
      of application kits, maturation of analysis software, connection to the existing
      databases and the possible ethical issues occurred with big data will be the key
      factors that determine whether this technology can substitute or supplement PCR
      CE, the mature technology, and be widely used for cases detection.

PMID- 29188674
TI  - [Research Progress on Abused Drugs Metabolic in vivo].
AB  - Under the catalysis of a variety of metabolic enzymes in vivo, such as UDP
      glucuronyl transferases, cytochrome P450, carboxylesterase, sulfotransferase,
      butyrylcholinesterase, catechol-O-methyl transferase and 6-morphine
      dehydrogenase, the drugs perform glucuronidation, hydrolysis, oxidation,
      sulfonation and other reactions, then translate into active or inactive
      metabolites, which are excreted through urination, bile or the other pathways at
      last. Different drugs own their different metabolic pathways. This paper
      introduces the studies about the metabolism of drugs in human and animal in
      recent years, such as morphine-like drugs, amphetamine, ketamine, cannabis and
      cocaine, and reviews the research progress about the sites of metabolism,
      metabolic enzymes, metabolites and physiological activity of those drugs
      metabolic in vivo.

PMID- 29188676
TI  - Autologous lipotransfer versus stromal vascular fraction enriched lipoinjection
      for diabetic foot wounds healing: a pilot study.
AB  - Chronic ulcers of the lower limbs represent a significant social and economic
      burden. Diabetes is a strong risk factor for development of chronic lesions.
      Adult stem cells and growth factors derived from the adipose tissue are among the
      most promising therapeutic strategies for hard to heal wounds. Fat grafts have
      been used for several decades to treat soft tissue deformities, but despite its
      excellent characteristics, the outcome was unpredictable, due to partial necrosis
      and resorption of the graft. Stem cells' enrichment of these grafts or their
      injection into the edges of the ulcers have shown encouraging results in various
      experimental settings. In this pilot study, we compared the standard of care to
      autologous lipotransfer and stromal vascular fraction (SVF) enriched
      lipoinjection in 30 patients with diabetic foot ulcers, showing clear superiority
      of SVF enriched lipoinjection in terms of percentage of reduction of ulcers size
      and healing time.

PMID- 29188675
TI  - The Origin and Development of Medical Jurisprudence in Xiangya.
AB  - The origin of medical jurisprudence in China can be traced back to as early as
      1920s, and since then, the discipline has undergone a great development. This
      paper, based on the disciplinary development of medical jurisprudence at Xiangya
      School of Medicine, illustrates its evolution in three aspects covering the
      scientific and theoretic foundation, legal system and policy support. The current
      investigation reflected a glimpse of the modern forensic science in China,
      providing useful historical reference for the development of Chinese forensic
      science.

PMID- 29188677
TI  - Scanning electron, 3D-confocal and stereotactic microscopies morpho-structural
      analysis of antibiotic-loaded cement porosity in three different formulations.
AB  - Chronic osteoarticular infections such as osteomyelitis or periprosthetic joint
      infection (PJI)have become a growing problem over the years. The "gold standard"
      in local antibiotic administration is still the antibiotic-loaded acrylic bone
      cement (ALABC) which is used in both prophylaxis, because it has been shown it
      can reduce the risk of infection and used in therapy during a "two-stage surgery"
      in PJI or in chronic osteomyelitis. We performed morphological analysis of three
      different formulations of antibiotic-loaded cement (ALABC) using techniques of
      light microscopy, scanning electron microscopy (SEM) and 3D immunofluorescence,
      in order to explain how the morphological aspects of cement could influence and
      modulate antibiotic elution.

PMID- 29188678
TI  - Posterolateral bundle reconstruction of the anterior cruciate ligament to restore
      rotational stability of the knee.
AB  - Only 5-10% of partial tears of the anterior cruciate ligament (ACL) are
      symptomatic, especially in high demand individuals or in patients practicing
      sports requiring rotational motions.. A certain preoperative diagnosis of this
      condition is challenging and often needs the combination of clinical examination,
      magnetic resonance imaging (MRI) and knee-laxity tool measurements. However, the
      arthroscopic examination of the torn ACL bundle is the most important factor in
      decision-making. Evidence in various studies have shown that the preservation of
      the ACL remnant and its surgical augmentation can bring important advantages in
      terms of vascularity and proprioception, resulting in better outcomes. The
      purpose of our paper was to describe the surgical technique of arthroscopic
      posterolateral (PL) bundle reconstruction with the preservation of the
      anteromedial (AM) bundle for ACL partial tears. Moreover, we reported the current
      knowledge about rationale, diagnosis and treatment of partial tears of ACL.

PMID- 29188679
TI  - A new surgical positioning system for robotic assisted minimally invasive spine
      surgery and transpedicular approach to the disc.
AB  - Minimally Invasive Spine Surgery (MISS) procedures for the treatment of spinal
      pathologies have experienced exponential growth due to improved techniques and
      decreased trauma to the patient. Several MISS procedures that require the use of
      a trans-pedicular cannula as a guiding tool for pedicle screw placement, delivery
      of biomaterials to the vertebral body or injection of biologics to the disc space
      have been described. Although these are clear advantages of MISS, the limited
      dissection and exposure may reduce the accuracy and stability of operation and
      make spine surgeons rely heavily on intraoperative fluoroscopy, raising concerns
      over the level of radiation exposure. Robot-assisted minimal invasive surgery has
      aroused more attention for its high precision and stability, minimizing risks of
      damage to neurovascular structures and diminishing harmful exposure to ionizing
      radiation. The aim of this paper is to describe and characterize a new surgical
      positioning system for for robotic assisted MISS. The system is conceived to be
      integrated in a surgical platform capable of supporting the surgeon in a new
      procedure to treat degenerative intervertebral disc disease. For this purpose, it
      is necessary to orientate a cannula in order to guide the bone drill along a
      planned route, to access the intervertebral disc through the pedicle and
      endplate. In particular, we describe a mechanism that percutaneously guides a
      cannula towards the intervertebral disc based on the acquisition of few
      fluoroscopic images. The design of the positioning system, with its features and
      constrains imposed by the presence of instrumentation and medical staff in the
      operating room, as well as the software for trajectory planning during surgery,
      are here described.

PMID- 29188680
TI  - Biomaterials as bone graft substitutes for spine surgery: from preclinical
      results to clinical study.
AB  - Vertebral fusion is performed in order to stabilize the spine in the presence of
      degenerative, traumatic or oncological pathologies that alter its stability. The
      autologous bone, harvested from the patient's iliac crest or from the lamina
      during surgery, is still considered the "gold standard" for spine fusion due to
      its osteogenic, osteoinductive and osteoconductive properties. However, several
      biological and synthetic bone substitutes have been introduced as alternatives
      for regenerating bone tissue. We have studied in particular the use of ceramic
      biomaterials prepared from hydroxypatite (HA), starting from in vitro analysis,
      through an in vivo study on ovine animal model and a post-market surveillance
      analysis, to finally design and perform a clinical study, which is ongoing in our
      Department. In the first step, HA-derived biomaterials were tested in vitro in
      the presence of bone marrow-derived human mesenchymal stem cells (hMSCs) and
      evaluated for their ability to activate precursor cells. In the second step, the
      biomimetic bone graft substitute SintLife(r) putty (MgHA) was evaluated in vivo.
      A posterolateral fusion procedure was applied on 18 sheep, where a fusion level
      was treated with MgHA, while the other level was treated with autologous bone.
      Microtomography and histological/histomorphometric analysis were performed six
      months of after surgery. In the third step, we reported the results of a post
      market surveillance study conducted on 4 independent cohorts of patients (total
      115 patients), in which HA-derived biomaterials were used as bone graft
      substitutes or extenders. Finally, a clinical study has been designed and
      approved by the Ethics Committee of our Institute and is currently ongoing. This
      study aims to evaluate the efficacy of the ceramic biomaterial SintLife(r) putty
      for bone replacement in patients treated by posterolateral fusion for
      degenerative spine disorders. HA biomaterials were effective in promoting the in
      vitro growth of hMSCs and their osteogenic differentiation. In the animal model,
      SintLife(r) putty has been effective in generating neo-formed bone tissue with
      morphological and structural features similar to those of the pre-existing bone.
      The post-market surveillance analysis has not reported any intra-operative nor
      early or late post-operative adverse events. Seven patients are currently
      recruited for the clinical trial designed to evaluate Sintlife efficacy for spine
      fusion (FU range: 1-7 months). No adverse events have been recorded. The first CT
      analysis performed at 6 months FU showed a good spine fusion. The study is
      ongoing. Our results, obtained from in vitro, preclinical and clinical studies,
      suggest that biomaterials derived from hydroxyapatite could be a valid
      alternative to autologous bone graft for vertebral fusion. This would potentially
      avoid or reduce the need of autologous bone harvesting and therefore, the risk of
      drawback-related side effects.

PMID- 29188681
TI  - Targeted muscle reinnervation for improved control of myoelectric upper limb
      prostheses.
AB  - Targeted muscle reinnervation (TMR) is a novel surgical technique developed to
      improve the control of myoelectric upper limb prostheses. Nerves transected by
      the amputation, which retain their original motor pathways even after being
      severed, are redirected to residual denervated muscles that serve as target for
      consequent reinnervation. Once the process is complete, reinnervated muscles will
      contract upon voluntary activation of transferred nerves while attempting to move
      missing regions of the amputated limb, generating EMG signals that can be
      recorded and used to control a prosthetic device. This allows creating new
      control sites that can overcome major drawbacks of conventional myoelectric
      prostheses by offering a more natural and intuitive control of prosthetic arms.
      TMR has been widely performed in individuals who underwent shoulder
      disarticulation amputation and transhumeral amputation since proximal amputations
      do not leave enough functional muscles exploitable to control independent degree
      of freedoms of multi-articulated prostheses. TMR application is currently under
      investigation in patients suffering further distal amputations, as well as for
      treating and preventing painful post-amputation neuromas. The purpose of this
      paper is to describe the physiologic basis and the surgical technique of TMR,
      reporting current knowledge on the clinical results.

PMID- 29188682
TI  - Biomass growth response to spatial pattern of variable-retention harvesting in a
      northern Minnesota pine ecosystem.
AB  - Variable-retention harvesting (VRH) is an approach for sustaining complex
      structure in managed forests. A criticism of VRH is that ecological benefits may
      come at a cost of reduced growth of regeneration, due to competition with
      residual trees. However, the spatial pattern of retention, i.e., dispersed or
      aggregated, in VRH systems can be manipulated to minimize suppression of
      regeneration, and resource limitation to regeneration might be mitigated by
      reduction of woody shrubs. Continued growth of the residual cohort will
      compensate for growth reduction of regeneration, although this may differ with
      retention pattern. We examined aboveground whole-stand biomass growth of trees in
      a VRH experiment in Pinus resinosa forest in Minnesota, USA. Treatments included
      dispersed retention, aggregated retention, and an uncut control, as well as a
      shrub treatment (reduced density or ambient). We addressed the following
      hypotheses: (1) biomass growth of a cohort of planted pine seedlings will be
      highest with aggregated rather than dispersed retention, (2) biomass growth of
      the planted seedlings will increase with shrub reduction, and (3) biomass growth
      of the residual overstory will be higher with dispersed rather than aggregated
      retention. Aboveground biomass growth of the planted pines ranged from 0.4 kg.ha
      1.yr-1 in the overstory-control-ambient-shrub treatment to 23 kg.ha-1.yr-1 in the
      aggregated-retention-shrub-reduction treatment. The difference between the
      control and the retention treatments was significant (P < 0.0001), but not
      between dispersed and aggregated retention (P = 0.97). Thus, our first hypothesis
      was not supported. In all treatments, biomass growth was significantly higher
      (>100% increase) with shrub reduction (P = 0.001), supporting our second
      hypothesis. Biomass growth of residual trees ranged from 2404 kg.ha-1.yr-1 in the
      uncut-control-ambient-shrub treatment to 1043 kg.ha-1.yr-1 in the aggregated
      retention-shrub-reduction treatment. Differences were significant between the
      control and retention treatments (P = 0.003), and marginally higher with
      dispersed vs. aggregated retention (P = 0.09), lending support to our third
      hypothesis. Our results suggest that managers have flexibility in application of
      VRH and can expect similar stand-level biomass growth of planted regeneration
      regardless of retention pattern, but somewhat higher stand-level biomass growth
      of retained trees with dispersed retention.

PMID- 29188683
TI  - Effects of forest management on California Spotted Owls: implications for
      reducing wildfire risk in fire-prone forests.
AB  - Management of many North American forests is challenged by the need to balance
      the potentially competing objectives of reducing risks posed by high-severity
      wildfires and protecting threatened species. In the Sierra Nevada, California,
      concern about high-severity fires has increased in recent decades but uncertainty
      exists over the effects of fuel-reduction treatments on species associated with
      older forests, such as the California Spotted Owl (Strix occidentalis
      occidentalis). Here, we assessed the effects of forest conditions, fuel
      reductions, and wildfire on a declining population of Spotted Owls in the central
      Sierra Nevada using 20 years of demographic data collected at 74 Spotted Owl
      territories. Adult survival and territory colonization probabilities were
      relatively high, while territory extinction probability was relatively low,
      especially in territories that had relatively large amounts of high canopy cover
      (>=70%) forest. Reproduction was negatively associated with the area of medium
      intensity timber harvests characteristic of proposed fuel treatments. Our results
      also suggested that the amount of edge between older forests and shrub/sapling
      vegetation and increased habitat heterogeneity may positively influence
      demographic rates of Spotted Owls. Finally, high-severity fire negatively
      influenced the probability of territory colonization. Despite correlations
      between owl demographic rates and several habitat variables, life stage
      simulation (sensitivity) analyses indicated that the amount of forest with high
      canopy cover was the primary driver of population growth and equilibrium
      occupancy at the scale of individual territories. Greater than 90% of medium
      intensity harvests converted high-canopy-cover forests into lower-canopy-cover
      vegetation classes, suggesting that landscape-scale fuel treatments in such
      stands could have short-term negative impacts on populations of California
      Spotted Owls. Moreover, high-canopy-cover forests declined by an average of 7.4%
      across territories during our study, suggesting that habitat loss could have
      contributed to declines in abundance and territory occupancy. We recommend that
      managers consider the existing amount and spatial distribution of high-canopy
      forest before implementing fuel treatments within an owl territory, and that
      treatments be accompanied by a rigorous monitoring program.

PMID- 29188684
TI  - Pattern recognition in long-term Sooty Shearwater data: applying machine learning
      to create a harvest index.
AB  - Rakiura Maori (New Zealand's southernmost group of indigenous peoples) have
      harvested the chicks of burrow-nesting Sooty Shearwaters (Titi; Puffinus griseus)
      for generations. As part of the harvest process, some families have maintained
      annual harvest diaries, some dating back to the 1950s. We used generalized
      boosted regression models, a machine-learning algorithm, to calculate a harvest
      index that takes into account factors that could impact the numbers of birds
      taken on any given hunt. For predicted vs. observed values, r2 was between 0.59
      and 0.90 for the nanao (first half of the season, when chicks are harvested from
      burrows during the day) and 0.67 and 0.88 for the rama (second half of the
      season, during which chicks are harvested from the surface at night). Exploration
      of the controlling factors of the models revealed that "day of season" plays an
      important role in predicting daily harvest during the second half of the season
      (the rama). The nightly tally in the rama peaked approximately halfway through
      (10-15 days in), which is probably related to the timing of birds emerging from
      burrows to fledge. The models also suggested that data from the rama (when chicks
      are 100-120 days old) may be the most suitable for long-term monitoring of
      populations of Sooty Shearwaters due to consistencies in calculated harvest
      indices between diaries. Nanao harvest indices, although less consistent, showed
      patterns similar to those of the rama. When comparing these data to the harvest
      indices calculated by general linear models by Clucas and colleagues, we found
      that the agreement between both indices was r2 = 0.31 and r2 = 0.59 for the nanao
      and rama, respectively. The use of machine learning to correct for extraneous
      factors (e.g., hunting effort, skill level, or weather) and to create
      standardized measures could be applied to other systems such as fisheries or
      terrestrial resource management.

PMID- 29188685
TI  - Functional connectivity experiments reflect routine movement behavior of a
      tropical hummingbird species.
AB  - Translocation experiments, in which researchers displace animals and then monitor
      their movements to return home, are commonly used as tools to assess functional
      connectivity of fragmented landscapes. Such experiments are purported to have
      important advantages of being time efficient and of standardizing "motivation" to
      move across individuals. Yet, we lack tests of whether movement behavior of
      translocated birds reflects natural behavior of unmanipulated birds. We compared
      the routine movement behavior of a tropical hummingbird, the Green Hermit
      (Phaethornis guy), to that of experimentally translocated individuals. We tested
      for differences in site selection patterns during movement at two spatial scales
      (point and path levels). We also compared movement rates between treatments.
      Behaviors documented during translocation experiments reflected those observed
      during routine movements. At the point level, both translocated and non
      translocated birds showed similar levels of preference for mature tropical
      forest. At the path level, step selection functions showed both translocated and
      non-translocated hummingbirds avoiding movement across non-forested matrix and
      selecting streams as movement corridors. Movement rates were generally higher
      during translocation experiments. However, the negative influence of forest cover
      on movement rates was proportionately similar in translocation and routine
      movement treatments. We report the first evidence showing that movement behavior
      of birds during translocation experiments is similar to their natural movement
      behavior. Therefore, translocation experiments may be reliable tools to address
      effects of landscape structure on animal movement. We observed consistent
      selection of landscape elements between translocated and non-translocated birds,
      indicating that both routine and translocation movement studies lead to similar
      conclusions regarding the effect of landscape structure and forest composition on
      functional connectivity. Our observation that hummingbirds avoid non-forest
      matrix and select riparian corridors also provides a potential mechanism for
      pollen limitation in fragmented tropical forest.

PMID- 29188686
TI  - Having our yards and sharing them too: the collective effects of yards on native
      bird species in an urban landscape.
AB  - Residential yards comprise a substantial portion of urban landscapes, and the
      collective effects of the management of many individual yards may "scale up" to
      affect urban biodiversity. We conducted bird surveys and social surveys in
      Chicago-area (Illinois, USA) residential neighborhoods to identify the relative
      importance of yard design and management activities for native birds. We found
      that groups of neighboring yards, in the aggregate, were more important for
      native bird species richness than environmental characteristics at the
      neighborhood or landscape scale. The ratio of evergreen to deciduous trees in
      yards and the percentage of yards with trees and plants with fruits or berries
      were positively associated with native bird species richness, whereas the number
      of outdoor cats had a negative association. The number of birdfeeders was not an
      important predictor for native species richness. We also found that migratory
      birds were observed on transects with more wildlife-friendly features in yards,
      and nonnative birds were observed on transects with greater numbers of outdoor
      cats and dogs. Our results highlight the potential importance of residential
      matrix management as a conservation strategy in urban areas.

PMID- 29188687
TI  - Population models for social species: lessons learned from models of Red-cockaded
      Woodpeckers (Picoides borealis).
AB  - Behavior can have major impacts on the population dynamics of social species and
      should be incorporated into demographic models to realistically evaluate
      population trends and extinction risk. We compared the predictions of a stage-
      and age-based matrix model, an individual-based model (IBM, developed in the
      program Vortex), and a spatially explicit individual-based model (SEPM) with the
      actual dynamics of a population of Red-cockaded Woodpeckers (RCW; Picoides
      borealis) in the Sandhills of North Carolina, USA. Predictions, including
      population size, composition, and growth rate, differed the most from actual
      population characteristics for models that did not incorporate social structure.
      The SEPM most closely predicted actual population dynamics, underestimating the
      population by 2.3%. This model, specifically developed to simulate RCW population
      dynamics, contains many of the features that we assert are important for
      adequately incorporating social behavior into demographic and population
      modeling. These features include the ability to (1) differentiate individuals
      based on their stage class, (2) capture the dynamics of the population at both
      the individual and group level, (3) incorporate the positive or negative effects
      of subdominants, (4) include environmental and demographic stochasticity, and (5)
      capture dispersal and other spatial factors. The RCW SEPM, although currently
      species-specific, provides a strong blueprint for how population models for
      social species could be constructed in the future when data allow.

PMID- 29188689
TI  - 'Two sisters' again.

PMID- 29188688
TI  - Cultivation can increase harvesting pressure on overexploited plant populations.
AB  - Captive breeding and cultivation of overharvested species is frequently proposed
      as a conservation strategy, yet there is little evidence under what conditions,
      if at all, the strategy is effective. We created a bioeconomic model to
      investigate the socioeconomic conditions favoring cultivation over wild
      harvesting and likely impacts on the wild population. We parameterize the model
      with the case study of illegal xate palm (Chamaedorea ernesti-augusti) harvesting
      in Belize and Guatemala. We examine how changes in law enforcement, a price
      premium for cultivated leaf, land ownership, and alternative income might affect
      decisions to cultivate and the impact of cultivation on wild populations. We show
      that those switching to cultivation are largely not wild harvesters because of
      barriers such as land ownership. We also find that if harvesters do switch to
      cultivation, they may have a negative effect on the wild population through
      harvesting of material to set up plantations. We found increasing alternative
      income reduces harvesting pressure and suggests the provision of alternative
      livelihoods would more directly reduce pressure on the wild population. Although
      schemes to encourage cultivation seem an appealing conservation intervention, we
      urge caution in assuming that people will readily adopt cultivation of wild
      harvested species or that this would necessarily reduce impacts on wild
      populations.

PMID- 29188690
TI  - Guidelines for Crowns, Fixed Bridges and Implants.

PMID- 29188691
TI  - How to Minimize Repeat Dental General Anaesthetics.
AB  - This article aims to provide general dental practitioners (GDPs) with the
      knowledge to improve their referrals primarily for children who they feel require
      a dental general anaesthetic. It discusses the impact of a general anaesthetic
      (GA) on a child and the financial impacts of dental general anaesthetics (DGAs).
      The risks of DGAs are well recognized and the ways in which the dental team in
      primary, secondary care and service commissioners can reduce the risk of repeat
      DGAs are discussed. Clinical relevance: Dentists should be aware of the risks
      involved in GA and the importance of reducing repeat DGAs.

PMID- 29188692
TI  - Complications of an Ageing Dentition Part 2: Restorative Management Options.
AB  - This is the second-part of this three-part series. The first paper discussed the
      occlusal and cracked tooth aetiological factors which may be responsible for
      restoration failure. This paper will outline the restorative options for cracked
      and root canal-treated teeth. It will also briefly give an overview of some of
      the potential endodontic complications commonly associated with failed
      restorations. The third, and final, part of the series will provide an overview
      of the previous papers and conclude with a case report. Clinical relevance:
      Failure of amalgam restorations is a commonly encountered clinical problem in
      general practice and no one case presents in the same way. Therefore, a competent
      endodontic diagnosis and implementation of the most appropriate, minimally
      invasive restorative option requires an adequate knowledge of the current
      literature.

PMID- 29188693
TI  - Diagnosis and Management of Chronic and Aggressive Periodontitis Part 2:
      Periodontal Management.
AB  - The first paper of this three-part series discussed periodontal disease
      pathogenesis and highlighted elements in the clinical assessment which will help
      the clinician to establish the diagnosis of chronic and aggressive periodontitis.
      This second paper will focus on the management of chronic and aggressive
      periodontitis. Finally, the diagnosis and management of chronic and aggressive
      periodontitis will be reviewed in the third part of the series using two clinical
      examples. Clinical relevance: This paper aims to provide the general dental
      practitioner with an understanding of the aim of periodontal treatment, the
      management of chronic and aggressive periodontitis and the prognosis of
      periodontally involved teeth.

PMID- 29188694
TI  - Supra-Therapeutic Oral Paracetamol Overdose in Adults: An Update for the Dental
      Team.
AB  - Paracetamol (acetaminophen) is a commonly used analgesic; its 'over the counter'
      availability, low cost and popularity amongst patients often make it the first
      choice for dental pain. It is in this that its potential toxicity, made more
      complicated by the ever extending range of paracetamol-containing products, make
      the understanding of this medication key to the safe management of patients
      presenting to surgery with dental pain. Clinical relevance: The purpose of this
      article is to supply dental practitioners with the knowledge to manage patients
      who present having taken an oral supra-therapeutic paracetamol overdose.
      Consideration is given to those patients who can be treated safely in primary
      care and to those who require transfer to Accident and Emergency (A&E).

PMID- 29188695
TI  - An Implant-Retained Obturator - A Case Study.
AB  - This case describes the oral rehabilitation of a patient following maxillary hemi
      section due to squamous cell carcinoma of the palate. Planned treatment was
      construction of a maxillary implant-supported obturator. Two dental implants were
      placed in his maxilla to aid the support and retention of an obturator. However,
      owing to bone availability, their angulation was suboptimal and compromised the
      retention of the obturator. This case describes alternative implant attachments
      to aid the retention and stability of implant-retained dentures constructed in
      cases with suboptimal implant placement. Clinical relevance: This case highlights
      the importance of careful planning for implant placement, and reinforces the need
      to plan the prostheses before implant surgery. This case highlights possible
      difficulties that can arise if implants are non-ideally angulated, and how to
      adapt restorations to manage such difficulties in cases with maxillary removable
      prostheses.

PMID- 29188696
TI  - Virtual Reality Exposure Therapy for Treatment of Dental Phobia.
AB  - popularity as an effective treatment for anxiety disorders. The purpose of this
      article is to determine the applicability of VRET in the treatment of dental
      phobia of two patients. Two case examples of female dental patients, aged 56 and
      24 years, who met the criteria for dental phobia according to the Phobia
      Checklist, illustrate the use of VRET in the dental setting. VRET that is used as
      a psychological treatment for dental fear and dental phobia can potentially be
      given by a non-specialist (for example dental assistant), thereby making it a
      cost-effective therapy for the treatment of dental phobia.Clinical relevance:
      This article is the first of its kind to demonstrate Virtual Reality Exposure
      Therapy (VRET) in the treatment of dental anxiety.

PMID- 29188697
TI  - The Immune System: Basis of so much Health and Disease: 4. Immunocytes.
AB  - The immune system is the body's primary defence mechanism against infections, and
      disturbances in the system can cause disease if the system fails in defence
      functions (in immunocompromised people), or if the activity is detrimental to the
      host (as in auto-immune and auto-inflammatory states). A healthy immune system is
      also essential to normal health of dental and oral tissues. This series presents
      the basics for the understanding of the immune system, this article covers cells
      of the immune system (immunocytes).  Clinical relevance: Modern dental clinicians
      need a basic understanding of the immune system as it underlies health and
      disease.

PMID- 29188698
TI  - Arteriovenous Malformation of the Jaws: a Black Hole for the GDP - A Case Report.
AB  - We report a case of a mandibular arteriovenous malformation in a 3-year-old
      child, who attended our department, and have carried out a literature
      review.Clinical relevance: Arteriovenous malformation (AVM) is a rare condition
      but clinicians need to be aware of it as this lesion can have potentially life
      threatening complications due to massive haemorrhage.

PMID- 29188699
TI  - Ceramic Fracture in Metal-Ceramic Restorations: The Aetiology.
AB  - All dental restorations are liable to failure during function. Failure could be
      biologic, aesthetic, mechanical or a combination. Ceramic restorations in
      particular, including metal-ceramics, are prone to mechanical fracture,
      especially the fracture of veneering porcelain. Fracture of a metal-ceramic
      restoration jeopardizes function as well as aesthetics. It is equally onerous to
      manage for both patient and dentist. Optimal management of such cases requires a
      detailed knowledge of the aetiology behind this phenomenon. The current paper
      aims to highlight possible causative factors involved in the mechanical failures
      of metal-ceramic restorations. Clinical relevance: Ceramic fracture in metal
      ceramic crowns and fixed partial dentures is routinely encountered in dental
      clinics. Knowledge of the aetiology is required to diagnose and manage such cases
      accurately as well as to avoid these errors in future.

PMID- 29188700
TI  - Dual Role of Subepithelial Connective Tissue Grafting in Regeneration of
      Periodontal Attachment Apparatus.
AB  - Periodontal plastic and aesthetic surgery are gaining significant momentum owing
      to the increasing aesthetic demands by patients. Along with the fulfilment of
      aesthetic needs, it is imperative that clinicians also enhance function. From
      these two important viewpoints, subepithelial connective tissue grafting remains
      an optimum treatment choice for periodontists when treating gingival recession
      defects accompanied by periodontal attachment apparatus breakdown. Clinical
      relevance: Subepithelial connective tissue grafting is a successful procedure in
      its dual role of gingival recession coverage and predictable periodontal
      regeneration.

PMID- 29188702
TI  - Technique Tips - Iatrogenesis and How to Prevent It.

PMID- 29188701
TI  - Clinical Challenges Q&A 31. Painful Lip.

PMID- 29188704
TI  - From overdiagnosis to overtreatment of small renal mas- can the chain be broken?
AB  - The incidence of small nephromas of less than four centimeters in size has
      increased over the past decades with the increasing number of imaging studies.
      The majority of these tumors are kidney cancers exhibiting large variation in
      their aggressiveness. Systematic surgical treatment of these tumors results in
      more harm than benefit especially for elderly patients having associated
      diseases. Biopsy procedures from tumors by current methods are safe. The
      challenge of active surveillance is to identify those nephromas that are no
      longer safely monitored before the cancer is beyond the reach of curative
      treatment.

PMID- 29188705
TI  - Individualized methods for the diagnosis and treatment of nonspecific lower back
      pain.
AB  - Lower back pain is globally the most common problem interfering with functional
      capacity, and the recognition of causes that are serious and require specific
      therapy is essential in its diagnosis. Provision of information for a person
      suffering from lower back pain is essential. In some patients psychosocial
      factors prolong the back pain and potential incapacity for work. For their
      evaluation several internationally validated surveys have been developed, which
      can be used to facilitate the identification of higher-risk patients. By using
      electronic data, our aim is to develop in Finland the assessment of individual
      risk of patients with lower back pain and their appropriate treatment.

PMID- 29188706
TI  - Highly Stretchable and Transparent Electromagnetic Interference Shielding Film
      Based on Silver Nanowire Percolation Network for Wearable Electronics
      Applications.
AB  - Future electronics are expected to develop into wearable forms, and an adequate
      stretchability is required for the forthcoming wearable electronics considering
      various motions occurring in human body. Along with stretchability, transparency
      can increase both the functionality and esthetic features in future wearable
      electronics. In this study, we demonstrate, for the first time, a highly
      stretchable and transparent electromagnetic interference shielding layer for
      wearable electronic applications with silver nanowire percolation network on
      elastic poly(dimethylsiloxane) substrate. The proposed stretchable and
      transparent electromagnetic interference shielding layer shows a high
      electromagnetic wave shielding effectiveness even under a high tensile strain
      condition. It is expected for the silver nanowire percolation network-based
      electromagnetic interference shielding layer to be beyond the conventional
      electromagnetic interference shielding materials and to broaden its application
      range to various fields that require optical transparency or nonplanar surface
      environment, such as biological system, human skin, and wearable electronics.

PMID- 29188707
TI  - Increasing Extracellular Free Fatty Acid Production in Escherichia coli by
      Disrupting Membrane Transport Systems.
AB  - Transposon mutagenesis was used to identify three mutants of E. coli that
      exhibited increased free fatty acid (FFA) production, which resulted from the
      disruption of genes related to membrane transport. Deletion of envR, gusC, and
      mdlA individually in a recombinant E. coli strain resulted in 1.4-, 1.8-, and 1.2
      fold increases in total FFA production, respectively. In particular, deletion of
      envR increased the percentage of extracellular FFA to 46%, compared with 29% for
      the control strain. Multiple deletion of envR, gusC, mdlA, ompF, and fadL had a
      synergistic effect on FFA production, resulting in high extracellular FFA
      production, comprising up to 50% of total FFA production. This study has
      identified new membrane proteins involved in FFA production and showed that
      genetic engineering targeting these membrane transporters is important to
      increase both total FFA and extracellular FFA production.

PMID- 29188708
TI  - Role of Polymer Segregation on the Mechanical Behavior of All-Polymer Solar Cell
      Active Layers.
AB  - An all-polymer bulk heterojunction (BHJ) active layer that removes the use of
      commonly used small molecule electron acceptors is a promising approach to
      improve the thermomechanical behavior of organic solar cells. However, there has
      been limited research on their mechanical properties. Here, we report on the
      mechanical behavior of high-performance blade-coated all-polymer BHJ films cast
      using eco-friendly solvents. The mechanical properties considered include the
      elastic modulus, crack onset strain, and cohesive fracture energy. We show that
      the mechanical behavior of the blend is largely unaffected by significant changes
      in the segregation characteristics of the polymers, which was varied
      systematically through solvent formulation. In comparison to a polymer:fullerene
      BHJ counterpart, the all-polymer films were found to have lower stiffness and
      increased ductility. Yet, the fracture energy of the all-polymer films is not
      significantly improved compared to that of the polymer:fullerene films. This
      study highlights that improved mechanical behavior of all-polymer systems cannot
      be assumed, and that details of the molecular structure, molecular weight, and
      film morphology play an important role in both the optoelectronic and mechanical
      properties. Furthermore, we show that simple composite modeling provides a
      predictive tool for the mechanical properties of the polymer blend films,
      providing a framework to guide future optimization of the mechanical behavior.

PMID- 29188709
TI  - High-Antifouling Polymer Brush Coatings on Nonpolar Surfaces via Adsorption-Cross
      Linking Strategy.
AB  - A new "adsorption-cross-linking" technology is presented to generate a highly
      dense polymer brush coating on various nonpolar substrates, including the most
      inert and low-energy surfaces of poly(dimethylsiloxane) and
      poly(tetrafluoroethylene). This prospective surface modification strategy is
      based on a tailored bifunctional amphiphilic block copolymer with benzophenone
      units as the hydrophobic anchor/chemical cross-linker and terminal azide groups
      for in situ postmodification. The resulting polymer brushes exhibited long-term
      and ultralow protein adsorption and cell adhesion benefiting from the high
      density and high hydration ability of polyglycerol blocks. The presented
      antifouling brushes provided a highly stable and robust bioinert background for
      biospecific adsorption of desired proteins and bacteria after secondary
      modification with bioactive ligands, e.g., mannose for selective ConA and
      Escherichia coli binding.

PMID- 29188710
TI  - Palladium-Catalyzed Sequential Vinylic C-H Arylation/Amination of 2-Vinylanilines
      with Aryl boronic Acids: Access to 2-Arylindoles.
AB  - A palladium-catalyzed selective and successive vinylic C-H arylation/amination of
      2-vinylanilines with arylboronic acids to generate indoles has been developed.
      This procedure represents a straightforward and practical approach to valuable
      multifunctionalized indoles.

PMID- 29188711
TI  - Tracking the Source of Carbon Dot Photoluminescence: Aromatic Domains versus
      Molecular Fluorophores.
AB  - Carbon dots (CDs) are an intriguing fluorescent material; however, due to a
      plethora of synthesis techniques and precursor materials, there is still
      significant debate on their structure and the origin of their optical properties.
      The two most prevalent mechanisms to explain them are based on polycyclic
      aromatic hydrocarbon domains and small molecular fluorophores, for instance,
      citrazinic acid. Yet, how these form and whether they can exist simultaneously is
      still under study. To address this, we vary the hydrothermal synthesis time of
      CDs obtained from citric acid and ethylenediamine and show that in the initial
      phase molecular fluorophores, likely 2-pyridone derivatives, account for the blue
      luminescence of the dots. However, over time, while the overall size of the CDs
      does not change, aromatic domains form and grow, resulting in a second, faster
      decay channel at similar wavelengths and also creating additional lower energetic
      states. Electrophoresis provides further evidence that the ensemble of CDs
      consists of several subsets with different internal structure and surface charge.
      The understanding of the formation mechanism enables a control of the chemical
      origin of these emitters and the ensuing optical properties of the CDs through
      synthetic means.

PMID- 29188712
TI  - Direct Wittig Olefination of Alcohols.
AB  - A base-promoted transition metal-free approach to substituted alkenes using
      alcohols under aerobic conditions using air as the inexpensive and clean oxidant
      is described. Aldehydes are relatively difficult to handle compared to
      corresponding alcohols due to their volatility and penchant to polymerize and
      autoxidize. Wittig ylides are easily oxidized to aldehydes and consequently form
      homo-olefination products. By the strategy of simultaneously in situ generation
      of ylides and aldehydes, for the first time, alcohols are directly transferred to
      olefins with no need of prepreparation of either aldehydes or ylides. Thus, the
      di/monocontrollable olefination of diols is accomplished. This synthetically
      practical method has been applied in the gram-scale synthesis of pharmaceuticals,
      such as DMU-212 and resveratrol from alcohols.

PMID- 29188713
TI  - Mining for Small Translated ORFs.
AB  - Peptides encoded by short open reading frames (sORFs) are usually defined as
      peptides <=100 aa long. Usually sORFs were ignored by automatic genome annotation
      programs due to the high probability of false discovery. However, improved
      computational tools along with a high-throughput RIBO-seq approach identified a
      myriad of translated sORFs. Their importance becomes evident as we are gaining
      experimental validation of their diverse cellular functions. This Review examines
      various computational and experimental approaches of sORFs identification as well
      as provides the summary of our current knowledge of their functional roles in
      cells.

PMID- 29188714
TI  - Secoheliosphanes A and B and Secoheliospholane A, Three Diterpenoids with Unusual
      seco-Jatrophane and seco-Jatropholane Skeletons from Euphorbia helioscopia.
AB  - Secoheliosphanes A (1) and B (2) and secoheliospholane A (3), possessing an
      unusual 7,8-seco-jatrophane skeleton and an unprecedented 9,10-seco-7,10
      epoxyjatropholane skeleton, respectively, were isolated from the whole plants of
      Euphorbia helioscopia, along with two biogenetically precursors, a new jatrophane
      diterpene, 2-epi-euphornin I (4) and a known jatrophane diterpene, euphoscopin A
      (5). Structures of 1-4 including absolute configurations were elucidated on the
      basis of spectroscopic data, X-ray crystallography, and chemical conversion.
      Compounds 1 and 2 were prepared from 4 and 5, respectively, confirming their
      structural assignments. Notably, 1 and 2 presented the first examples of seco
      jatrophane-type diterpenoids and 3 featured a novel 5/6/7/7-fused tetracyclic
      ring skeleton. Among them, compound 2 showed modest activity against HSV-1 with
      IC50 value of 6.41 MUM.

PMID- 29188715
TI  - Strain-Gradient Effect in Gas Sensors Based on Three-Dimensional Hollow
      Molybdenum Disulfide Nanoflakes.
AB  - A novel three-dimensional transition metal dichalcogenide (TMD) structure
      consisting of seamless hollow nanoflakes on two-dimensional basal layers was
      synthesized by a one-step chemical vapor deposition method. Here, we demonstrate
      that the as-grown nanoflakes are formed on an organic promoter layer which served
      as a positive template and are swollen at the grain boundaries by the bubbling
      effect. TMD nanosheets with hollow nanoflakes are successfully applied as
      chemical sensors, and it was found that their gas adsorption property is strongly
      related to the internal strain gradient resulting from the variation in the
      lattice parameter. This result is consistent with the theoretical prediction in
      previous studies. Our chemical vapor deposition-based approach is an efficient
      way to generate TMD-based nanostructures over a large surface area for various
      practical applications such as chemical sensors.

PMID- 29188716
TI  - Hybrid Organic/Inorganic Perovskite-Polymer Nanocomposites: Toward the
      Enhancement of Structural and Electrical Properties.
AB  - Hybrid organic/inorganic perovskite nanoparticles (NPs) have garnered remarkable
      research attention because of their promising photophysical properties. New and
      interesting properties emerge after combining perovskite NPs with semiconducting
      materials. Here, we report the synthesis and investigation of a composite
      material obtained by mixing CH3NH3PbBr3 nanocrystals with the semiconducting
      polymer poly(3-hexylthiophene) (P3HT). By the combination of structural
      techniques and optical and magnetic spectroscopies we observed multiple effects
      of the perovskite NPs on the P3HT: (i) an enlargement of P3HT crystalline
      domains, (ii) a strong p-doping of the P3HT, and (iii) an enhancement of
      interchain order typical of H-aggregates. These observations open a new avenue
      toward innovative perovskite NP-based applications.

PMID- 29188717
TI  - A Protective Role for Triacylglycerols during Apoptosis.
AB  - Triacylglycerols (TAGs) are one of the major constituents of the glycerolipid
      family. Their main role in cells is to store excess fatty acids, and they are
      mostly found within lipid droplets. TAGs contain acyl chains that vary in length
      and degree of unsaturation, resulting in hundreds of chemically distinct species.
      We have previously reported that TAGs containing polyunsaturated fatty acyl
      chains (PUFA-TAGs) accumulate via activation of diacylglycerol acyltransferases
      during apoptosis. In this work, we show that accumulation of PUFA-TAGs is a
      general phenomenon during this process. We further show that the accumulated PUFA
      TAGs are stored in lipid droplets. Because membrane-residing PUFA phospholipids
      can undergo oxidation and form reactive species under increased levels of
      oxidative stress, we hypothesized that incorporation of PUFAs into PUFA-TAGs and
      their localization within lipid droplets during apoptosis limit the toxicity
      during this process. Indeed, exogenous delivery of a polyunsaturated fatty acid
      resulted in a profound accumulation of PUFA phospholipids and rendered cells more
      sensitive to oxidative stress, causing reduced viability. Overall, our results
      support the concept that activation of TAG biosynthesis protects cells from lipid
      peroxide-induced membrane damage under increased levels of oxidative stress
      during apoptosis. As such, targeting triacylglycerol biosynthesis in cancer cells
      might represent a new approach to promoting cell death during apoptosis.

PMID- 29188718
TI  - Polyplex Micelles with Phenylboronate/Gluconamide Cross-Linking in the Core
      Exerting Promoted Gene Transfection through Spatiotemporal Responsivity to
      Intracellular pH and ATP Concentration.
AB  - Polyplexes as gene delivery carriers require integrated functionalities to
      modulate intracellular trafficking for efficient gene transfection. Herein, we
      developed plasmid DNA (pDNA)-loaded polyplex micelles (PMs) from poly(ethylene
      glycol)-based block catiomers derivatized with 4-carboxy-3-fluorophenylboronic
      acid (FPBA) and d-gluconamide to form pH- and ATP-responsive cross-linking in the
      core. These PMs exhibited robustness in the extracellular milieu and smooth
      endosomal escape after cellular uptake, and they facilitated pDNA decondensation
      triggered by increased ATP concentration inside of the cell. Laser confocal
      microscopic observation revealed that FPBA installation enhanced the endosomal
      escapability of the PMs; presumably, this effect resulted from the facilitated
      endo-/lysosomal membrane disruption triggered by the released block catiomers
      with hydrophobic FPBA moieties in the side chain from the PM at lower pH
      condition of endo-/lysosomes. Furthermore, the profile of intracellular pDNA
      decondensation from the PMs was monitored using Forster resonance energy transfer
      measurement by flow cytometry; these observations confirmed that PMs optimized
      for ATP-responsivity exerted effective intracellular decondensation of loaded
      pDNA to attain promoted gene transfection.

PMID- 29188719
TI  - Improved Carrier Transport in Perovskite Solar Cells Probed by Femtosecond
      Transient Absorption Spectroscopy.
AB  - CH3NH3PbI3 perovskite thin films have been deposited on glass/indium tin
      oxide/hole transport layer (HTL) substrates, utilizing two different materials as
      the HTLs. In the first configuration, the super hydrophilic polymer poly(3,4
      ethylenedioxythiophene)-poly(styrenesulfonate), known as PEDOT:PSS, was employed
      as the HTL material, whereas in the second case, the nonwetting
      poly(triarylamine) semiconductor polymer, known as PTAA, was used. It was found
      that when PTAA is used as the HTL material, the averaged power conversion
      efficiency (PCE) of the perovskite solar cells (PSCs) remarkably increases from
      12.60 to 15.67%. To explore the mechanism behind this enhancement, the
      aforementioned perovskite/HTL arrangements were investigated by time-resolved
      transient absorption spectroscopy (TAS) performed under inert conditions. By
      means of TAS, the charge transfer, carrier trapping, and hole injection dynamics
      from the photoexcited perovskite layers to the HTL can be directly monitored via
      the characteristic bleaching profile of the perovskite at ~750 nm. TAS studies
      revealed faster relaxation times and decay dynamics when the PTAA polymer is
      employed, which potentially account for the enhanced PCE observed. The TAS
      results are correlated with the structure and crystalline quality of the
      corresponding perovskite films, investigated by scanning electron microscopy, X
      ray diffraction, atomic force microscopy, micro-photoluminescence, and
      transmittance spectroscopy. It is concluded that TAS is a benchmark technique for
      the understanding of the carrier transport mechanisms in PSCs and constitutes a
      figure-of-merit tool toward their efficiency improvement.

PMID- 29188720
TI  - Surface Reactivity of Li2MnO3: First-Principles and Experimental Study.
AB  - This article deals with the surface reactivity of (001)-oriented Li2MnO3 crystals
      investigated from a multitechnique approach combining material synthesis, X-ray
      photoemission spectroscopy (XPS), scanning electron microscopy, Auger electron
      spectroscopy, and first-principles calculations. Li2MnO3 is considered as a model
      compound suitable to go further in the understanding of the role of tetravalent
      manganese atoms in the surface reactivity of layered lithium oxides. The
      knowledge of the surface properties of such materials is essential to understand
      the mechanisms involved in parasitic phenomena responsible for early aging or
      poor storage performances of lithium-ion batteries. The surface reactivity was
      probed through the adsorption of SO2 gas molecules on large Li2MnO3 crystals to
      be able to focus the XPS beam on the top of the (001) surface. A chemical mapping
      and XPS characterization of the material before and after SO2 adsorption show in
      particular that the adsorption is homogeneous at the micro- and nanoscale and
      involves Mn reduction, whereas first-principles calculations on a slab model of
      the surface allow us to conclude that the most energetically favorable species
      formed is a sulfate with charge transfer implying reduction of Mn.

PMID- 29188721
TI  - Comparison of major bleeding risk in patients with non-valvular atrial
      fibrillation receiving direct oral anticoagulants in the real-world setting: a
      network meta-analysis.
AB  - OBJECTIVE: To conduct a systematic literature review (SLR) and network meta
      analysis (NMA) of real-world studies comparing major bleeding risk among patients
      with non-valvular atrial fibrillation (NVAF) on direct oral anticoagulants
      (DOACs) or warfarin. METHODS: Systematic searches were conducted in MEDLINE and
      Embase for full-text articles published between January 1, 2003 and March 18,
      2017. Eligible studies compared at least two of the following in a real-world
      setting: warfarin, apixaban, dabigatran, rivaroxaban, or edoxaban. A Bayesian NMA
      was conducted to estimate hazard ratios (HRs) for major bleeding using a random
      effects model. RESULTS: Eleven studies were included in the NMA. Nine studies
      included DOACs vs Warfarin comparisons, and four studies included DOACs vs DOACs
      comparisons (two studies included both comparisons). Median follow-up duration
      ranged from 2.6-31.2 months. No evidence was identified for edoxaban. Apixaban
      was associated with a significantly lower risk of major bleeding compared to
      other oral anticoagulants (warfarin HR = 0.58; 95% credible interval [CrI] = 0.48
      0.69; dabigatran = 0.73; 0.61-0.87; rivaroxaban = 0.55; 0.46-0.66). Dabigatran
      was associated with a significantly lower risk than warfarin (0.79; 0.71-0.88)
      and rivaroxaban (0.76; 0.67-0.85), and rivaroxaban was not statistically
      different from warfarin (1.05; 0.91-1.19). Sensitivity analyses with standard
      dose and sponsorship showed consistent results. CONCLUSION: DOACs were associated
      with lower or similar risk of major bleeding compared with warfarin in NVAF
      patients. Apixaban was associated with a significantly lower risk of major
      bleeding than other DOACs. Dabigatran was associated with a significantly lower
      risk of major bleeding compared to rivaroxaban and warfarin.

PMID- 29188722
TI  - Three new sesquiterpenes from the stems of Nicotiana tabacum and their
      bioactivities.
AB  - Three new sesquiterpenes, methyl 4-isopropyl-7-methoxy-6-methylnaphthalene-1
      carboxylate (1), methyl 2-hydroxy-4-isopropyl-7-methoxy-6-methylnaphthalene-1
      carboxylate (2), and methyl 2-hydroxy-6-(hydroxymethyl)-4-isopropyl-7
      methoxynaphthalene-1-carboxylate (3), together with three known sesquiterpenes (4
      6), were isolated from the stems of Nicotiana tabacum. Their structures were
      determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies.
      The results showed that compounds 2, 3, and 5 exhibited high anti-TMV activity
      with inhibition rates of 33.6, 35.8, and 36.7%. Compounds 1-6 showed weak
      inhibitory activities against some tested human tumor cell lines (NB4, A549,
      SHSY5Y, PC3, and MCF7) with IC50 values in the range of 6.7-9.6 MUM.

PMID- 29188723
TI  - Cryogenic dermal injuries to the chest secondary to inhalational abuse of
      keyboard cleaner.

PMID- 29188724
TI  - Dissecting the heterogeneity of stage III non-small-cell lung cancer through
      incorporation of grade and histology.
AB  - AIM: This study evaluated a grade-integrated American Joint Committee on Cancer
      (AJCC) staging system for non-small-cell lung cancer. PATIENTS & METHODS:
      Surveillance, Epidemiology and End Results database was queried through SEER*Stat
      program. Through recursive partitioning analysis and subsequent decision-tree
      formation, suggested grade-modified stages were formulated. RESULTS: All pairwise
      hazard ratio comparisons among AJCC eighth stages were significant (p < 0.05)
      except stage IIIB versus stage IIIC; while all pairwise hazard ratio comparisons
      among modified AJCC stages were significant (p < 0.05). When stratified by
      histology, there was a benefit for the modified system among adenocarcinoma
      rather than squamous cell carcinoma patients. CONCLUSION: Grade integration
      improved the prognostication of the AJCC staging system particularly for stage
      III adenocarcinoma. This should be considered in future revisions of the AJCC
      staging system.

PMID- 29188725
TI  - Trial-Based Functional Analysis Informs Treatment for Vocal Scripting.
AB  - Research on trial-based functional analysis has primarily focused on socially
      maintained challenging behaviors. However, procedural modifications may be
      necessary to clarify ambiguous assessment results. The purposes of this study
      were to evaluate the utility of iterative modifications to trial-based functional
      analysis on the identification of putative reinforcement and subsequent treatment
      for vocal scripting. For all participants, modifications to the trial-based
      functional analysis identified a primary function of automatic reinforcement. The
      structure of the trial-based format led to identification of social attention as
      an abolishing operation for vocal scripting. A noncontingent attention treatment
      was evaluated using withdrawal designs for each participant. This noncontingent
      attention treatment resulted in near zero levels of vocal scripting for all
      participants. Implications for research and practice are presented.

PMID- 29188726
TI  - Smoking to fit a stigmatised identity? A qualitative study of marginalised young
      people in Australia.
AB  - In countries with comprehensive tobacco control, smoking is increasingly
      denormalised, with smokers subject to social stigmatisation. Qualitative research
      and commentary about denormalisation and stigma has largely focused on the impact
      on current or former smokers. Little attention has been given to the interaction
      between existing stigma among socially marginalised and disadvantaged young
      people and its role in smoking uptake, maintenance and resistance to quitting, or
      remaining a non-smoker. This article draws on a qualitative (grounded theory)
      study of young people aged 16-25 years who attended social services for at-risk
      youth in an inner city area in Australia, to explore the intersection between
      stigmatised identity and smoking in a context of increasing smoking
      denormalisation. Drawing on theoretical conceptualisations of stigma, we outline
      processes by which participants accept and apply social labels, internalise or
      distance themselves from stigmatised identities, and the influence of labelling
      on smoking trajectories, to demonstrate how the persistent dilemma of stigma
      shapes and reinforces smoking behaviour. The study highlights the need for
      tobacco control initiatives to align and integrate with broader initiatives to
      address structural inequality and social disadvantage.

PMID- 29188727
TI  - The optimal treatment of metastatic hormone-naive prostate cancer: abiraterone
      acetate or docetaxel?
AB  - AIM: To determine whether abiraterone acetate or docetaxel should be regarded as
      the current standard of care for metastatic hormone-naive prostate cancer
      (mHNPC). METHODS & MATERIALS: A network meta-analysis (NMA) using the frequentist
      approach and generalized pairwise modeling was computed. RESULTS: The results of
      this NMA favored abiraterone acetate over docetaxel-based regimens (hazard ratio:
      0.79; 95% CI: 0.64-0.99) in patients with mHNPC. The results also suggest a
      reconsideration of the role of prednisone in view of the absence of a survival
      benefit (hazard ratio: 0.98; 95% CI: 0.59-1.65) with its use. CONCLUSION: Despite
      the paucity of direct comparative evidence, the results of this NMA favor the use
      of abiraterone acetate in the first-line treatment of mHNPC.

PMID- 29188728
TI  - Triterpenoids from the aerial parts of Lantana camara.
AB  - Two new pentacyclic triterpenoids lancamarinic acid and lancamarinin have been
      obtained from the aerial parts of Lantana camara Linn. They were characterized as
      22beta-acetoxy-3,25-epoxy-3alpha-hydroxyolean-12-en-28-oic acid and methyl 3,25
      epoxy-3alpha-hydroxy-11-oxo-22beta-senecioyloxyolean-12-en-28-oate, respectively,
      through chemical transformation and exhaustive spectroscopic studies.

PMID- 29188729
TI  - Aspiration as a Function of Age, Sex, Liquid Type, Bolus Volume, and Bolus
      Delivery Across the Healthy Adult Life Span.
AB  - OBJECTIVES: The purpose of this investigation was to examine, via flexible
      endoscopic evaluation of swallowing (FEES), factors that affect penetration and
      aspiration during swallowing across the adult lifespan. METHODS: Healthy adults
      (N = 203) across the third to ninth decades of life participated. Penetration
      Aspiration Scale (PAS) scores were assessed during FEES as a function of age,
      sex, liquid type (water and skim, 2%, and whole milk), volume (5, 10, 15, and 20
      ml), and delivery (cup and straw). RESULTS: The PAS scores differed significantly
      by liquid type ( P < .0001) and age group ( P < .0001). In general, PAS scores
      were higher for milk versus water swallows and for older age groups. Significant
      interactions of liquid type by age ( P = .0042) and sex by volume ( P = .020)
      were also evidenced. In addition, the odds of penetration and aspiration
      increased significantly with milks compared to water and age ( P < .05).
      Increased bolus volume also increased the odds of aspiration ( P < .05).
      CONCLUSIONS: Aspiration may be an underappreciated phenomenon in healthy adults.
      The inclusion of both water and milk test boluses of various volumes during FEES
      may be important for the appropriate assessment of adult penetration and
      aspiration.

PMID- 29188730
TI  - Experiences of loss and relationship quality in couples living with dementia.
AB  - Couples living with dementia face multiple losses in their relationship, and may
      experience changes in their overall sense of relationship quality. These topics
      have predominantly been researched from the caring partner's perspective
      therefore, this study aimed to explore how couples adapt to relational losses to
      maintain quality in their relationship from the perspective of both partners.
      Using a constructivist grounded theory approach 10 spousal dyads, where one
      partner has a diagnosis of dementia, engaged in a joint interview. The results
      revealed three master themes: consolidating us, contextual positioning, and
      living well together, as well as an overarching theme of 'turning to and away'.
      The findings are discussed in relation to theories of loss and family adaptation,
      and implications for clinical practice and future research are proposed.

PMID- 29188731
TI  - Quality nursing care in dementia specific care units: A scoping review.
AB  - : Background The concept of quality nursing care in a dementia specific unit is
      perceived as being subject to the interpretation of individuals, nurses and
      healthcare organisations. As the number of dementia diagnoses increases,
      understanding what constitutes quality nursing care within dementia specific care
      units is vital to inform policy makers and healthcare organisations globally.
      Efforts to identify quality nursing care and improve dementia care within
      dementia specific care units, may significantly reduce the financial and
      emotional burden of care-giving and improve the quality of life for individuals
      living with dementia. This scoping review aimed to examine current literature to
      gain an understanding of what constitutes quality nursing care in a dementia
      specific care unit. Design and methods Five electronic databases (CINAHL,
      MEDLINE, ProQuest, Social Sciences Citation Index and Ovid) were used to search
      for articles published in English between 2011 and 2016 focusing on a definition
      of quality nursing care within dementia specific care units. FINDINGS: Twenty
      journal articles were identified. From these articles, two content themes were
      identified: Challenges in the provision of quality nursing care in dementia
      specific care units, and Standardised approach to quality nursing care in a
      dementia specific care unit. The articles contained the following research
      designs, controlled pre-test and post-test design ( n = 1), focus group
      interviews ( n = 1), cross sectional survey ( n = 6), semi structured interviews
      ( n = 3), narrative review ( n = 1), survey ( n = 2), literature review ( n = 3),
      systematic review ( n = 1), and prospective longitudinal cohort study ( n = 2).
      Conclusions The concept of quality nursing care in a dementia specific unit
      remains subject to the interpretation of individuals, nurses and healthcare
      organisations, with current literature unable to provide a clear definition.
      Further research into what constitutes quality nursing care in dementia specific
      care units is recommended.

PMID- 29188732
TI  - Parolee-Parole Officer Rapport: Does It Impact Recidivism?
AB  - Parole officers are an integral part of parolees' reentry process and success.
      Few studies, however, have examined whether the quality of the relationship
      between parolees and their parole officer influences outcomes such as recidivism.
      This study assesses how recidivism is affected by the quality of the relationship
      that parolees have with their parole officers. Using the Serious and Violent
      Offender Reentry Initiative (SVORI) dataset, we use parolees' perceptions of
      their relationship with their parole officer to determine whether they have
      established a positive or negative relationship, and whether these types of
      relationships differentially affect recidivism. Results show that parolees who
      have a negative relationship with their parole officer have higher rates of
      recidivism, while a positive relationship lowers parolees' likelihood of
      recidivating. An implication of this study emphasizes parole officer training
      that develops positive, high-quality relationships with parolees. Further
      implications are discussed below.

PMID- 29188733
TI  - Investigational drugs in clinical trials for Hidradenitis Suppurativa.
AB  - INTRODUCTION: Hidradenitis suppurativa is a chronic skin disease with a
      significant unmet need for treatment options. Randomized controlled trials are
      few and only a single drug (adalimumab) has Hidradenitis as a registered
      indication. Areas covered: The clinicaltrials.gov and the EudraCT clinical trials
      register for reported trials on Hidradenitis Suppurativa was searched on the 22
      06-2017. Trials for upcoming new drugs for HS are reported focusing on drugs in
      phase I and II trials. Expert opinion: Currently, MABp1, Secukinumab, CJM112,
      Apremilast and IFX-1 are being investigated in Phase I and II trials and offer
      theoretical and promising new treatment options. A trial with the drug MEDI8968
      has been terminated with disappointing results. Metformin, Botulinum Toxin B,
      Provodine, Benzoyl Peroxide and intralesional triamcinolone are being tested as
      well. Treatment of Hidradenitis remains a challenge and quality RTCs are needed.
      Studies indicates a range of potential targets for therapy such as interleukin-1
      and interleukin-17, but 'broad-spectrum' immunosuppressants like
      phosphodiesterase-4 inhibitors are being examined as well. A range of outcomes,
      including Physician Global Assessment, Sartorius scores and hidradenitis
      suppurativa clinical response are used in these trials, making future meta
      analysis of the data difficult.

PMID- 29188734
TI  - Psychiatric (Axis I) and personality (Axis II) disorders and subjective
      psychiatric symptoms in chronic tinnitus.
AB  - OBJECTIVE: Chronic tinnitus has been associated with several psychiatric
      disorders. Only few studies have investigated these disorders using validated
      diagnostic interviews. The aims were to diagnose psychiatric and personality
      disorders with structured interviews, to assess self-rated psychiatric symptoms
      and elucidate temporal relations between psychiatric disorders and tinnitus.
      DESIGN: Current and lifetime DSM-IV diagnoses of axis-I (psychiatric disorders)
      and axis-II (personality disorders) were assessed using structured clinical
      interviews (SCID-I and -II). Current subjective psychiatric symptoms were
      evaluated via self-rating instruments: the Symptom Check List-90 (SCL-90), the
      Beck Depression Inventory, and the Dissociative Experiences Scale (DES). STUDY
      SAMPLE: 83 patients (mean age 51.7, 59% men) with chronic, disturbing tinnitus
      and a median Tinnitus Handicap Inventory score of 32. RESULTS: The rates of
      lifetime and current major depression were 26.5% and 2.4%. The lifetime rate of
      obsessive-compulsive personality disorder (type C) was 8.4%. None of the patients
      had cluster B personality disorder or psychotic symptoms. The SCL-90 subscales
      did not differ from the general population, and median DES score was low, 2.4.
      CONCLUSIONS: Tinnitus patients are prone to episodes of major depression and
      often also have obsessive-compulsive personality features. Psychiatric disorders
      seem to be comorbid or predisposing conditions rather than consequences of
      tinnitus. Clinical trial reference: ClinicalTrials.gov (ID NCT 01929837).

PMID- 29188735
TI  - Clinical efficacy and safety of cefepime-tazobactam in hospitalized patients in
      South India.

PMID- 29188736
TI  - N-octyl-N-arginine-chitosan micelles for gambogic acid intravenous delivery:
      characterization, cell uptake, pharmacokinetics, and biodistribution.
AB  - OBJECTIVE: The deeper research of N-octyl-N-arginine chitosan (OACS) as
      intravenous delivery was characterized, cell uptake study, pharmacokinetics, and
      biodistribution of OACS micelles (GA-OACS) were investigated. SIGNIFICANCE:
      Gambogic acid (GA) can inhibit the growth of various cancer cells. However, the
      short elimination half-life time and treatment without targeting limits its
      application. OACS was synthesized as delivery carrier for GA by us, but the
      deeper characterization of OACS, such as molecular modeling, pharmacokinetics,
      and biodistribution were not investigated. METHODS: Gambogic acid loaded OACS
      micelles (GA-OACS) were evaluated by the molecular modeling, characterized by
      TEM, DLS, IR, 1HNMR, XRD. Confocal laser scanning microscope and flow cytometry
      were analyzed for cell uptake study. Imaging analysis was used to show the
      distribution of OACS in vivo directly, pharmacokinetics and biodistribution were
      also investigated. RESULTS: The molecular modeling result showed that GA could
      encapsulated stably in the core of OACS micelles. TEM, IR, 1HNMR, and XRD also
      suggested that GA was encapsulated in amorphous form in the core of OACS
      micelles. AUC and elimination half-life of GA-OACS were all increased by 1.5-fold
      and 2.0-fold compared with GA-ARG in rat, respectively. Biodistribution study
      indicated that GA-OACS was distributed mainly in the liver. GA amount in the
      kidney and heart was greatly reduced in the GA-OACS group. From the imaging
      analysis, OACS distribution in the liver was the most. CONCLUSIONS: OACS was an
      excellent carrier for GA intravenous delivery to prolong half-life. Moreover,
      OACS targeted on liver.

PMID- 29188737
TI  - Eruptive cherry angiomas developing in a patient treated with ramucirumab.

PMID- 29188739
TI  - Factors influencing the educational impact of Mini-CEX and DOPS: A qualitative
      synthesis.
AB  - INTRODUCTION: The educational impact of Mini-CEX and DOPS varies greatly and can
      be influenced by several factors. However, there is no comprehensive analysis and
      synthesis of the described influencing factors. METHODS: To fill this gap, we
      chose a two-step approach. First, we performed a systematic literature review and
      selected articles describing influencing factors on the educational impact of
      Mini-CEX and DOPS. Second, we performed a qualitative synthesis of these factors.
      RESULTS: Twelve articles were included, which revealed a model consisting of four
      themes and nine subthemes as influencing factors. The theme context comprises
      "time for Mini-CEX/DOPS" and "usability of the tools", and influences the users.
      The theme users comprises "supervisors' knowledge about how to use Mini
      CEX/DOPS", "supervisors' attitude to Mini-CEX/DOPS", "trainees' knowledge about
      Mini-CEX/DOPS", and "trainees' perception of Mini-CEX/DOPS". These influence the
      implementation of Mini-CEX and DOPS, including "observation" and "feedback". The
      theme implementation directly influences the theme outcome, which, in addition to
      the educational impact, encompasses "trainees' appraisal of feedback".
      CONCLUSIONS: Our model of influencing factors might help to further improve the
      use of Mini-CEX and DOPS and serve as basis for future research.

PMID- 29188738
TI  - Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting
      carriers for ischemia-reperfusion-induced acute renal injury.
AB  - In an attempt to improve therapeutic efficacy of dexamethasone (DXM)-loaded solid
      lipid nanoparticles (NPs) for renal ischemia-reperfusion injury (IRI)-induced
      acute renal injury (AKI), sialic acid (SA) is used as a ligand to target the
      inflamed vascular endothelium. DXM-loaded SA-conjugated polyethylene glycol
      (PEG)ylated NPs (SA-NPs) are prepared via solvent diffusion method and show the
      good colloidal stability. SA-NPs reduce apoptotic human umbilical vein
      endothelial cells (HUVECs) via downregulating oxidative stress-induced Bax,
      upregulating Bcl-xL, and inhibiting Caspase-3 and Caspase-9 activation. Cellular
      uptake results suggest SA-NPs can be specifically internalized by the inflamed
      vascular endothelial cells (H2O2-pretreated HUVECs), and the mechanism is
      associated with the specific binding between SA and E-selectin receptor expressed
      on the inflamed vascular endothelial cells. Bio-distribution results further
      demonstrated the enhanced renal accumulation of DXM is achieved in AKI mice
      treated with SA-NPs, and its content is 2.70- and 5.88-fold higher than those
      treated with DXM and NPs at 6 h after intravenous administration, respectively.
      Pharmacodynamic studies demonstrate SA-NPs effectively ameliorate renal functions
      in AKI mice, as reflected by improved blood biochemical indexes,
      histopathological changes, oxidative stress levels and pro-inflammatory
      cytokines. Moreover, SA-NPs cause little negative effects on lymphocyte count and
      bone mineral density while DXM leads to severe osteoporosis. It is concluded that
      SA-NPs provide an efficient and targeted delivery of DXM for ischemia-reperfusion
      induced injury-induced AKI, with improved therapeutic outcomes and reduced
      adverse effects.

PMID- 29188740
TI  - The effect of tinnitus specific intracochlear stimulation on speech perception in
      patients with unilateral or asymmetric hearing loss accompanied with tinnitus and
      the effect of formal auditory training.
AB  - OBJECTIVES: Previous studies show that intracochlear electrical stimulation
      independent of environmental sounds appears to suppress tinnitus, even long-term.
      In order to assess the viability of this potential treatment option it is
      essential to study the effects of this tinnitus specific electrical stimulation
      on speech perception. DESIGN: A randomised, prospective crossover design. STUDY
      SAMPLE: Ten patients with unilateral or asymmetric hearing loss and severe
      tinnitus complaints. RESULTS: The audiological effects of standard clinical CI,
      formal auditory training and tinnitus specific electrical stimulation were
      investigated. Results show that standard clinical CI in unilateral or asymmetric
      hearing loss is shown to be beneficial for speech perception in quiet, speech
      perception in noise and subjective hearing ability. Formal auditory training does
      not appear to improve speech perception performance. However, CI-related
      discomfort reduces significantly more rapidly during CI rehabilitation in
      subjects receiving formal auditory training. Furthermore, tinnitus specific
      electrical stimulation has neither positive nor negative effects on speech
      perception. CONCLUSIONS: In combination with the findings from previous studies
      on tinnitus suppression using intracochlear electrical stimulation independent of
      environmental sounds, the results of this study contribute to the viability of
      cochlear implantation based on tinnitus complaints.

PMID- 29188741
TI  - Adherence to Oral Medications During Maintenance Therapy Among Children and
      Adolescents With Acute Lymphoblastic Leukemia: A Medication Refill Analysis.
AB  - Adherence to oral medications during maintenance therapy is essential for
      pediatric patients with acute lymphoblastic leukemia. Self-reported or electronic
      monitoring of adherence indicate suboptimal adherence, particularly among
      particular sociodemographic groups. This study used medication refill records to
      examine adherence among a national sample of pediatric patients with acute
      lymphoblastic leukemia. Patients in a national claims database, aged 0 to 21
      years with a diagnosis of acute lymphoblastic leukemia and in the maintenance
      phase of treatment, were included. Medication possession ratios were used as
      measures of adherence. Overall adherence and adherence by sociodemographic groups
      were examined. Adherence rates were 85% for 6-mercaptopurine and 81% for
      methotrexate. Adherence was poorer among patients 12 years and older. Oral
      medication adherence rates were suboptimal and similar to or lower than
      previously documented rates using other methods of assessing adherence. Refill
      records offer a promising avenue for monitoring adherence. Additional work to
      identify groups most at-risk for poor adherence is needed. Nurses are well
      positioned to routinely monitor for medication adherence and to collaborate with
      the multidisciplinary team to address barriers to adherence.

PMID- 29188742
TI  - Management of pathologic node-positive disease following initial surgery for
      clinical T1-2 N0 esophageal cancer: patterns of care and outcomes from the
      national cancer data base.
AB  - PURPOSE: Although clinical T1-2N0 esophageal cancer (EC) is often initially
      surgically resected (without neoadjuvant therapy), several studies have
      illustrated substantial rates of discovering pathologically node-positive
      disease. This study evaluated national practice patterns of adjuvant therapy for
      this population. METHODS: The National Cancer Database (NCDB) was queried (2004
      2013) for patients with cT1-2N0M0 EC that received up-front surgery
      (esophagectomy/local techniques) with subsequent discovery of nodal metastasis.
      Patients receiving any neoadjuvant therapy were excluded. Multivariable logistic
      regression determined factors predictive of receiving adjuvant therapy. Kaplan
      Meier analysis evaluated overall survival (OS), and Cox proportional hazards
      modeling determined variables associated with OS. Propensity score matching
      assessed groups in a balanced manner while reducing indication biases. RESULTS:
      Altogether, 715 patients met inclusion criteria; 114 (16%) underwent adjuvant
      chemotherapy, 183 (26%) chemoradiation, 16 (2%) radiotherapy alone, and 402 (56%)
      observation. Observation was more likely performed with advanced age (p = .002)
      and at nonacademic centers (p = .001). Median OS in the respective cohorts were
      42.6, 35.1, 22.2, and 27.0 months. Both chemotherapy and chemoradiation were
      statistically similar (p = .462) but superior to observation (p < .05 for both).
      There was a survival benefit to any adjuvant treatment (median OS 38.5 vs. 27.0
      months, p < .001), which persisted after propensity matching (median OS 35.1 vs.
      24.3 months, p < .001). On multivariable analysis, any adjuvant treatment was
      independently associated with improved OS, along with treatment at an academic
      center (p < .05 for all). CONCLUSIONS: In the largest study to date evaluating
      patterns of care for pN + disease following resection of cT1-2N0 EC, a strikingly
      high proportion of patients were observed. Adjuvant treatment, ideally
      chemotherapy or chemoradiation, independently correlated with higher survival,
      and should be considered in able patients. Treatment at academic facilities also
      associated with higher survival, which has implications for patient counseling.

PMID- 29188743
TI  - A case study on Discrete Wavelet Transform based Hurst exponent for epilepsy
      detection.
AB  - Epileptic seizures are manifestations of epilepsy. Careful analysis of EEG
      records can provide valuable insight and improved understanding of the mechanism
      causing epileptic disorders. The detection of epileptic form discharges in EEG is
      an important component in the diagnosis of epilepsy. As EEG signals are non
      stationary, the conventional frequency and time domain analysis does not provide
      better accuracy. So, in this work an attempt has been made to provide an overview
      of the determination of epilepsy by implementation of Hurst exponent (HE)-based
      discrete wavelet transform techniques for feature extraction from EEG data sets
      obtained during ictal and pre ictal stages of affected person and finally
      classifying EEG signals using SVM and KNN Classifiers. The The highest accuracy
      of 99% is obtained using SVM.

PMID- 29188744
TI  - Contraception in adolescents with intellectual disability.
AB  - OBJECTIVES: The aims of the study were to investigate the reasons for first
      gynaecological consultation in adolescents with intellectual disability (ID) and
      assess how contraception is prescribed with regard to the different contraceptive
      methods, their medical indications, adverse effects and compliance, in comparison
      with a group of adolescents without ID. METHODS: A retrospective case-control
      study was conducted among 200 adolescents with ID (group A) and a control group
      of 200 adolescents without ID (group B). RESULTS: The main reasons for
      gynaecological consultation in group A were 'need for contraception' (46.5% in
      group A vs 32.0% in group B, p = .003) and abnormal uterine bleeding (42.0% in
      group A vs 27.0% in group B, p = .002). Contraception was prescribed in 80.0% of
      the adolescents in both groups. Combined oral contraception was prescribed in
      83.1% in group A vs. 91.3% in group B (p = .03). The transdermal patch was more
      prevalent in group A (6.3% vs. 0.6% in group B, p = .006). Other contraceptive
      methods were similar between the two groups. In group B there were 5.0%
      unintended pregnancies vs no cases in group A (p = .001). Sexual abuse occurred
      similarly in both groups (2.5% in group A vs 2.0% in group B, p = not
      significant). CONCLUSION: The need for contraception in adolescents with ID is a
      frequent reason for gynaecological consultation, despite their younger age and
      lower number who are sexually active. Combined oral contraception is the most
      prescribed method in adolescents with ID; however, the transdermal patch also
      plays an important role in this group.

PMID- 29188745
TI  - Bariatric surgery versus conservative management for morbidly obese patients in
      Spain: a cost-effectiveness analysis.
AB  - BACKGROUND: We assessed the cost-effectiveness of bariatric surgery (BS) versus
      conservative management (CM) for treating morbid obesity in Spain. METHODS: We
      developed a probabilistic Markov model to estimate health outcomes, quality
      adjusted life years (QALY), life years gained (LYG), and costs over lifetime and
      10-year horizons. Combined common BS procedures were compared with CM. Clinical
      and utility inputs were obtained from the literature and resource use and costs
      from local sources (?2017). RESULTS: Over the 10-year horizon, BS led to a cost
      increment of ?9,386 and 1.6 additional QALY (?5,966/QALY). Leading to 0.6 LYG and
      4.4 QALY gains and ?300/patient average cost savings over lifetime, BS could
      potentially significantly reduce diabetes and cardiovascular disease risk over
      the considered horizons. Despite short-term cost reductions, surgery delay may
      lead to significant clinical benefits loss. CONCLUSIONS: Compared to CM, BS is a
      more effective and less costly alternative for treating morbid obesity in Spain.

PMID- 29188747
TI  - Development and characterization of clay facial mask containing turmeric extract
      solid dispersion.
AB  - OBJECTIVE: To develop clay facial mask containing turmeric extract solid
      dispersion (TESD) for enhancing curcumin water solubility and permeability and to
      determine suitable clay based facial mask. METHODS: The TESD were prepared by
      solvent and melting solvent method with various TE to polyvinylpyrrolidone (PVP)
      K30 mass ratios. The physicochemical properties, water solubility, and
      permeability were examined. The effects of clay types on physical stability of
      TESD, water adsorption, and curcumin adsorption capacity were evaluated. RESULTS:
      The TESD prepared by solvent method with a TE to PVP K30 mass ratio of 1:2 showed
      physically stable, dry powders, when mixed with clay. When TESD was dissolved in
      water, the obtained TESD micelles showed spherical shape with mean size of ~100
      nm resulting in a substantial enhancement of curcumin water solubility, ~5 mg/ml.
      Bentonite (Bent) and mica (M) showed the highest water adsorption capacity. The
      TESD's color was altered when mixed with Bent, titanium dioxide (TiO2) and zinc
      oxide (ZnO) indicating curcumin instability. Talcum (Talc) showed the greatest
      curcumin adsorption followed by M and kaolin (K), respectively. Consequently, in
      vitro permeation studies of the TESD mixed with Talc showed lowest curcumin
      permeation, while TESD mixed with M or K showed similar permeation profile as
      free TESD solutions. The developed TESD-based clay facial mask showed lower
      curcumin permeation as compared to those formulations with Tween 80. CONCLUSION:
      The water solubility and permeability of curcumin in clay based facial mask could
      be improved using solid dispersion technique and suitable clay base composed of
      K, M, and Talc.

PMID- 29188748
TI  - Regional dialect perception across the lifespan: Identification and
      discrimination.
AB  - Although adult listeners can often identify a talker's region of origin based on
      his or her speech, young children typically fail in dialect perception tasks, and
      little is known about the development of regional dialect representations from
      childhood into adulthood. This study explored listeners' understanding of the
      indexical importance of American English regional dialects across the lifespan.
      Listeners between 4 and 79 years old in the Midwestern United States heard
      talkers from the Midland, Northern, Southern, and New England regions in two
      regional dialect perception tasks: identification and discrimination. The results
      showed that listeners as young as 4-5 years old understand the identity-marking
      significance of some regional dialects, although adult-like performance was not
      achieved until adolescence. Further, the findings suggest that regional dialect
      perception is simultaneously impacted by the specific dialects involved and the
      cognitive difficulty of the task.

PMID- 29188746
TI  - Can neuroimaging help aphasia researchers? Addressing generalizability,
      variability, and interpretability.
AB  - Neuroimaging studies of individuals with brain damage seek to link brain
      structure and activity to cognitive impairments, spontaneous recovery, or
      treatment outcomes. To date, such studies have relied on the critical assumption
      that a given anatomical landmark corresponds to the same functional unit(s)
      across individuals. However, this assumption is fallacious even across
      neurologically healthy individuals. Here, we discuss the severe implications of
      this issue, and argue for an approach that circumvents it, whereby: (i)
      functional brain regions are defined separately for each subject using fMRI,
      allowing for inter-individual variability in their precise location; (ii) the
      response profile of these subject-specific regions are characterized using
      various other tasks; and (iii) the results are averaged across individuals,
      guaranteeing generalizabliity. This method harnesses the complementary strengths
      of single-case studies and group studies, and it eliminates the need for post hoc
      "reverse inference" from anatomical landmarks back to cognitive operations, thus
      improving data interpretability.

PMID- 29188749
TI  - Bleeding during veno-venous ECMO cannot reliably be predicted by rotational
      thrombelastometry (ROTEMTM).
AB  - INTRODUCTION: Veno-venous extracorporeal membrane oxygenation (vvECMO) used for
      respiratory support is associated with clinical bleeding in at least one third of
      patients. Mechanisms promoting bleeding, like acquired von Willebrand syndrome,
      cannot be identified by routine coagulation tests. This study was performed to
      evaluate rotational Thrombelastography (ROTEMTM) for specific results predicting
      bleeding events during vvECMO. METHODS: Five hundred and thirty-four ROTEMTM
      analyses of 57 patients over 574 days have been evaluated. Patients were graded
      into three groups according to the severity of bleeding, following the Freiburg
      ECMO bleeding assessment. ROTEMTM results and basic as well as comprehensive
      laboratory coagulation tests have been compared among the three groups and
      overall between defined time points. RESULTS: Fourteen patients (25 %) presented
      without bleeding, 22 patients (39 %) showed mild bleeding and 21 patients (36 %)
      became evident with relevant clinical bleeding. No bleeding shock and no fatal
      bleeding event occurred. No case of hyperfibrinolysis was observed. Neither a
      statistical difference for ECMO blood flow nor duration of therapy among the
      groups could be shown. The only significant difference was clotting time (CT) in
      the InTEM analysis, with a median (IQR) of 175 (37.5) seconds in Group 1, 190
      (54.5) seconds in Group 2 and 204 (90) seconds in Group 3. When comparing overall
      ROTEMTM analyses between defined time points, continuous worsening of CT can be
      found in ExTEM, FibTEM and ApTEM. Reduced A10, A20 and congruently maximum clot
      firmness, especially, developed in ExTEM and ApTEM and with a minor
      characteristic in InTEM, but not in FibTEM. ROTEMTM and coagulation-parameter
      results before 19 clinical relevant bleeding episodes compared to all other
      results only showed differences in FibTEM. CONCLUSION: ROTEMTM as a functional
      viscoelastic analysis does not provide additional information to basic and
      comprehensive laboratory tests during vvECMO. Bleeding events cannot be predicted
      by the means of specific ROTEMTM results.

PMID- 29188750
TI  - Perceptions about participation in a 12-week walking program for people with
      severe knee osteoarthritis: a qualitative analysis.
AB  - PURPOSE: To explore the perceptions of people with severe knee osteoarthritis and
      increased cardiovascular risk about participating in a walking program. METHODS:
      Qualitative study using semistructured interviews for people with severe knee
      osteoarthritis and increased cardiovascular risk who participated in a 12-week
      walking program. Interviews were audiotaped, transcribed verbatim, member
      checked, coded and themes developed using thematic analysis. Findings were
      triangulated with quantitative data including pain, function and cardiovascular
      risk factors from previously reported data. RESULTS: Twenty-one participants were
      interviewed after the completion of the walking program. The main theme
      identified was the preoccupation with the knee including pain, damage and the
      view that surgery was required. Three subthemes to emerge were (i) the perception
      of functional, cardiovascular and psychosocial benefits with the walking program;
      (ii) that supervision, monitoring and commitment were important enablers; and
      (iii) external factors such as ill-health, weather and the environment were key
      barriers. The perceived functional and cardiovascular benefits converged with
      results from quantitative data. CONCLUSIONS: Even when patients with severe
      osteoarthritis of the knee report other benefits from participating in a walking
      program, the core theme to emerge was their preoccupation with knee pain, knee
      damage and the view that they needed a knee replacement. Implications for
      Rehabilitation Patients with severe osteoarthritis of the knee and moderate
      cardiovascular risk reported functional, cardiovascular and psychosocial benefits
      from participating in a walking program. Despite patients reporting functional,
      cardiovascular and psychosocial benefits, the core theme to emerge was their
      preoccupation with knee pain, knee damage and the view that they needed a knee
      replacement. The core theme highlights the challenges in promoting physical
      activity for patients with severe knee osteoarthritis.

PMID- 29188751
TI  - Go with the flow: GEF-H1 mediated shear stress mechanotransduction in
      neutrophils.
AB  - Neutrophils in circulation experience significant shear forces due to blood flow
      when they tether to the vascular endothelium. Biochemical and biophysical
      responses of neutrophils to the physical force of flowing blood modulate their
      behavior and promote tissue recruitment under pro-inflammatory conditions.
      Neutrophil mechanotransduction responses occur through mechanisms that are not
      yet fully understood. In our recent work, we showed that GEF-H1, a RhoA specific
      guanine nucleotide exchange factor (GEF), is required to maintain neutrophil
      motility and migration in response to shear stress. GEF-H1 re-localizes to
      flottilin-rich uropods in neutrophils in response to fluid shear stress and
      promotes spreading and crawling on activated endothelial cells. GEF-H1 drives
      cellular contractility through myosin light chain (MLC) phosphorylation
      downstream of the Rho-ROCK signaling axis. We propose that GEF-H1-dependent cell
      spreading and crawling in shear stress-dependent neutrophil recruitment from the
      vasculature are due to the specific localization of Rho-induced contractility in
      the uropod.

PMID- 29188752
TI  - Patterns of Adverse Childhood Experiences in Juveniles Who Sexually Offended.
AB  - Juveniles who sexually offended (JSOs) are differentially burdened with adverse
      childhood experiences (ACEs). The present study used Latent Class Analysis (LCA)
      to derive subtypes of JSOs according to their patterns of 10 different ACEs. An
      extensive file analysis of 322 male JSOs ( M = 14.14, SD = 1.94) revealed five
      subtypes with (a) multiple (9.0%), (b) mainly family related (17.1%), (c) mainly
      peer related (21.7%), (d) mainly neglectful (18.6%), and (e) little/no (33.5%)
      ACEs. Differences among ACE subtypes with regard to several offense and victim
      characteristics (e.g., the use of penetration or violence, the choice of a child,
      a male, a stranger, or multiple victims) were examined. Whereas no differences
      were found for the use of physical violence or the choice of male, stranger, or
      multiple victims, binary logistic regressions revealed associations of the
      multiple-ACE subtype with the choice of a child victim, the family-ACE subtype
      with the use of penetration as well as further nonsexual delinquency, the peer
      ACE subtype with the use of penetration and the choice of a child victim, and the
      neglect-subtype with the choice of a child victim. Additional analyses including
      single ACE categories instead of LCA-derived subtypes supported these results.
      Findings highlight the need for a comprehensive consideration of ACEs in research
      and clinical work to understand developmental pathways to juvenile sexual
      offending.

PMID- 29188753
TI  - The Use of Language in Hospice Care and the Impact on Patients and Families.
AB  - This narrative account describes the perspective of family members experience of
      hospice care.

PMID- 29188754
TI  - "It's Sort of Reaffirmed to Me That I'm Not a Monster, I'm Not a Terrible
      Person": Sex Offenders' Movements Toward Desistance via Peer-Support Roles in
      Prison.
AB  - Individuals incarcerated in prisons across the United Kingdom and abroad are able
      to volunteer for a variety of peer-support roles, which are characterized by
      prisoner-to-prisoner helping. Some research has found that such roles can
      represent turning points in the lives of those who have offended and encourage
      movements toward desistance. This proposed redemptive influence is argued to
      result from the prosocial behaviors that such roles appear to elicit in their
      holders. The present study aims to explore the mechanics of this claimed
      influence. While a limited amount of research has attempted this on a general
      offending population, no research has done so with a sample of sexual offenders.
      Given the intensive treatment programs involved in such contexts, and the
      requirements for sexual offenders to demonstrate reduced risk, the authors
      believe those serving time for sexual offenses represent an important sample on
      which to explore the potentially redemptive properties of peer-support roles. To
      this end, 13 peer supporters participated in semistructured interviews.
      Transcripts were analyzed using a phenomenologically oriented thematic analysis.
      Results suggest that sexual offenders who adopt peer-support roles are able to
      live up to desired selves by "doing good" in prison, "giving back," and
      consequently resisting negative labels. These benefits have been theoretically
      linked with better reintegration outcomes for sexual offenders, who are publicly
      denigrated in the extreme and find it especially difficult to (re)integrate.
      Suggestions regarding the future utility of such schemes are offered.

PMID- 29188755
TI  - Approach and Avoidance Tendencies Toward Picture Stimuli of (Pre-)Pubescent
      Children and Adults: An Investigation in Pedophilic and Nonpedophilic Samples.
AB  - The presence of pedophilic sexual interests is considered of high importance for
      predicting recidivism among individuals who have committed sexual offenses.
      However, objective and valid assessment methods that are robust against
      confounding issues such as cognitive capacity and manipulation are sparse. We
      applied the Approach-Avoidance Task (AAT) for detecting sexual interests in 38
      pedophilic men (18 primarily attracted to boys) and 27 male nonpedophilic (11
      gay) participants. The AAT relies on automatic approach and avoidance tendencies,
      independent of cognitive abilities such as memory capacity and intelligence.
      Approach-avoidance tendencies toward stimuli depicting seminude prepubescent boys
      and girls as well as men and women are reported. The results were consistent with
      previous research on the utility of the AAT: Except for pedophiles attracted to
      girls, the mean AAT scores (approach minus avoidance reaction time for each
      stimulus category) were positive only for stimuli of the preferred category. A
      multivariate binary logistic regression approach revealed 80% overall accuracy in
      differentiating pedophilic from nonpedophilic participants.

PMID- 29188756
TI  - Psychosocial Correlates of Attitudes Toward Male Sexual Violence in a Sample of
      Financial Crime, Property Crime, General Violent, and Homicide Offenders.
AB  - Although those currently serving prison sentences for sexual violence can be
      identified and receive treatment, the number of prisoners with a history of
      sexual violence against female partners is unknown. Methods to identify prisoners
      with a proclivity for such violence and accurately assess the risk they pose
      before and after incarceration are therefore required. Here, we aimed to assess
      the level of sexually violent attitudes within dating relationships and to
      examine their associations with experiences of child abuse and neglect (CAN),
      psychopathic personality traits, prisonization, number of incarcerations, age,
      years of schooling, relationship status, and parenting among different types of
      offenders (financial crime, property crime, general violent, and homicide
      offenders). Data were collected among a large systematically selected sample of
      adult male inmates ( N = 1,123). We demonstrated that sexual violence-supportive
      attitudes appear to be a function of child sexual abuse and psychopathic
      personality traits, and may be developed through early socialization experiences
      as well as incarceration. Practical implications of current findings are
      discussed.

PMID- 29188757
TI  - Folate receptor-targeted multimodal fluorescence mesosilica nanoparticles for
      imaging, delivery palladium complex and in vitro G-quadruplex DNA interaction.
AB  - New folic acid-conjugated mesoporous silica nanoparticles were synthesized. The
      effect of calcination at 400 degrees C on the fluorescence characteristics of
      mesoporous silica nanoparticles were studied in this work. The formed carbon dots
      (CDs) from calcination were used as the source of fluorescence. 3
      Aminopropyltriethoxysilane was then used to amine-functionalized the fluorescent
      surface of mesoporous silica nanoparticles. The amine fluorescence mesoporous
      silica nanoparticles (amine-FMSNs) were coupled with folic acid (FA) as the
      target ligand (FA-amine-FMSNs). A palladium complex was also synthesized and
      encapsulated in the FA-amine-FMSNs yielded fluorescent property with therapeutic
      effect. The in vitro release of an entrapped palladium complex from FA-amine
      FMSNs was studied under physiological conditions. According to the cell viability
      assay on HeLa (positive FR) and Hep-G2 (negative FR) cells, the targeted delivery
      system inhibited the growth of positive FR with higher selectivity compared with
      negative FR cells. Also, the emission CDs were used for fluorescence microscopic
      imaging. To confirm anti-cancer activity of the palladium complex, the
      interaction between palladium complex and G-quadruplex DNA were investigated with
      multi-spectroscopic methods and molecular modeling. The molecular docking studies
      showed a partial intercalation mode with a 4.27 * 105 M-1 binding constant.

PMID- 29188758
TI  - Utility of intraoperative computed tomography for cochlear implantation in
      patients with difficult anatomy.
AB  - OBJECTIVE AND IMPORTANCE: To describe cases that illustrate the utility of
      intraoperative computed tomography (CT) in cochlear implantation of patients with
      difficult temporal bone anatomy. CLINICAL PRESENTATION: A 2-year-old male with
      congenital X-linked stapes gusher syndrome and a 2-year-old female with enlarged
      vestibular aqueduct underwent successful cochlear implantation with the help of
      intraoperative CT. In the latter case, the initial intraoperative C-arm
      fluoroscopy suggested malposition of the electrode, however, was not able to
      provide details for adjustments. In both cases, intraoperative CT changed the
      insertion technique of the operating surgeon and allowed for improved electrode
      positioning. A 47-year-old female with polyostotic fibrous dysplasia and a 55
      year-old male with post-meningitis near-total cochlear obliteration underwent
      successful cochlear implantation with confirmation of electrode position with
      intraoperative CT. In the former case, the image-guided navigation system was
      also implemented. Finally, a 72-year-old female underwent cochlear implantation
      during which intraoperative C-arm fluoroscopy suggested intra-cochlear insertion.
      However, postoperative CT showed the electrode extending into the internal
      auditory canal (IAC), illustrating the limitations of C-arm fluoroscopy.
      INTERVENTION: Intraoperative CT imaging and image-guided navigation system.
      CONCLUSION: When faced with challenging temporal bone anatomy, intraoperative CT
      can provide critical details of the patient's microanatomy that allows for
      improved localization of the electrode and adjustments in operative techniques
      for successful cochlear implantation.

PMID- 29188759
TI  - Identifying free-text features to improve automated classification of structured
      histopathology reports for feline small intestinal disease.
AB  - The histologic evaluation of gastrointestinal (GI) biopsies is the standard for
      diagnosis of a variety of GI diseases (e.g., inflammatory bowel disease [IBD] and
      alimentary lymphoma [ALA]). The World Small Animal Veterinary Association (WSAVA)
      Gastrointestinal International Standardization Group proposed a reporting
      standard for GI biopsies consisting of a defined set of microscopic features. We
      compared the machine classification accuracy of free-text microscopic findings
      with those represented in the WSAVA format with a diagnosis of IBD and ALA.
      Unstructured free-text duodenal biopsy pathology reports from cats ( n = 60) with
      a diagnosis of IBD ( n = 20), ALA ( n = 20), or normal ( n = 20) were identified.
      Biopsy samples from these cases were then scored following the WSAVA guidelines
      to create a set of structured reports. Three supervised machine-learning
      algorithms were trained using the structured and then the unstructured reports.
      Diagnosis classification accuracy for the 3 algorithms was compared using the
      structured and unstructured reports. Using naive Bayes and neural networks,
      unstructured information-based models achieved higher diagnostic accuracy (0.90
      and 0.88, respectively) compared to the structured information-based models (0.74
      and 0.72, respectively). Results suggest that discriminating diagnostic
      information was lost using current WSAVA microscopic guideline features. Addition
      of free-text features (number of plasma cells) increased WSAVA auto
      classification performance. The methodologies reported in our study represent a
      way of identifying candidate microscopic features for use in structured
      histopathology reports.

PMID- 29188760
TI  - Surgical complications and their management in cochlear implantees less than 5
      years of age: The KEMH Pune experience.
AB  - OBJECTIVE: To evaluate the incidence of surgical complications of cochlear
      implantation and their management at K.E.M. hospital Pune. METHODS: It was a
      retrospective and prospective observational study conducted from February 2006 to
      December 2015 in the paediatric age group of 12 months to 5 years (213 cases).
      The complications were divided into major and minor groups based on the
      classification proposed by Cohen and Hoffman. RESULTS: The mean age of
      implantation was 3.03 years (ranged from 1 to 4.11 years). Sixteen patients had
      complications. The overall incidence of complications was 7.51% which comprised
      of major (2.34%) and minor (5.16%) complications. The commonest major
      complications were flap-related issues and the commonest minor complication was
      facial paresis. DISCUSSION: The results of our study were compared with similar
      studies conducted in the past. All surgical complications were treated
      conservatively or surgically with success. CONCLUSIONS: Cochlear implantation is
      the safe procedure in children between the age group of 12 months and less than 5
      years.

PMID- 29188761
TI  - Metabolic syndrome and cardiovascular risk assessment tools' estimations of 10
      year cardiovascular risk: a population-based study.
AB  - BACKGROUND: This cross-sectional study determines the association between 10-year
      cardiovascular disease (CVD) risk, estimated using four CVD risk assessment
      tools, and metabolic syndrome (MetS) in northern Iranian general population.
      METHODS: We used the data of 2371 participants aged 40-74 without any history of
      diabetes mellitus from a cohort study conducted among 6140 subjects aged 10-90
      years in northern Iran. Three definitions of MetS were used. The four CVD risk
      assessment tools used to estimate the 10-year CVD risk included pooled cohort
      equations of ACC/AHA, Systematic Coronary Risk Evaluation (SCORE) equations (for
      low-risk and high-risk European countries), and Framingham general cardiovascular
      risk profile for use in primary care. Logistic regression was used to determine
      the association between various definitions of MetS and 10-year CVD risk of >=5%,
      >= 7.5%, and >=10%, based on the related risk assessment tools. RESULTS: In men,
      univariate logistic regression analysis showed the strongest association between
      10-year risk of >=0.1 estimated by Framingham risk profile and the three
      definitions of MetS. In women, the 10-year risks by Framingham risk profile and
      SCORE equations for high-risk European countries had stronger associations with
      various definitions of MetS than others. No significant associations were
      detected between estimated risks of four risk assessment tools and various
      definitions of MetS in multivariate logistic regression analyses. CONCLUSION: No
      independent associations were observed between estimations of 10-year CVD risk
      using four risk assessment tools and various definitions of MetS.

PMID- 29188762
TI  - Developmental Trajectories of Child Sexual Behaviors on the Path of Sexual
      Behavioral Problems: Evidence From a Prospective Longitudinal Study.
AB  - There is little information about the onset and the developmental course of child
      sexual behavior problems (SBPs), including sexually intrusive behaviors (SIBs).
      Using data from the Vancouver Longitudinal Study on the Psychosocial Development
      of Children, the current study examined the presence of distinct patterns of
      sexual development among children. A normative sample of preschoolers ( N = 354)
      with a small clinical subsample were followed from age 3 to 8 with repetitive
      measurements of sexual behaviors using a revised version of Child Sexual Behavior
      Inventory. Semiparametric group-based modeling identified four distinct sexual
      development trajectories: the very low (10.5%), the low declining (27.8%), the
      moderate stable (48.3%), and the high-rate increasing (13.4%). In contrast to the
      other developmental trajectories found, the high-rate-increasing pattern showed
      that sexual behaviors became increasingly extensive after school entry. Children
      characterized by this developmental pattern, especially boys, were more likely to
      be involved in SIBs after elementary school entry than those in the other groups.
      Findings highlight the presence of multiple developmental trajectories of sexual
      development with significantly different behavioral patterns after school entry.

PMID- 29188763
TI  - Prothrombotic State in a Patient With Acute Liver Failure: The Question of
      Anticoagulation.
AB  - A 35-year-old male with acute liver failure due to acute hepatitis B virus
      infection was admitted to the intensive care unit with significant hepatocellular
      injury, cholestasis, abnormal standard coagulation tests, normal rotational
      thromboelastometry indices, and without signs of bleeding. He underwent emergency
      liver transplantation without requiring blood product transfusions or
      procoagulant treatments. The postoperative course was complicated by deep vein
      thrombosis and impending hepatic artery thrombosis treated with unfractionated
      heparin, aspirin, and intravenous prostacyclin. The patient survived and made a
      full neurological recovery. This case revealed the presence of a prothrombotic
      state due to a rebalanced coagulation system in a patient with liver dysfunction
      that was not identifiable by standard coagulation tests. This case emphasizes
      that identifying and treating coagulopathy is very difficult in liver failure
      patients and requires specific diagnostic and therapeutic strategies.

PMID- 29188764
TI  - Assessing the performance of methodological search filters to improve the
      efficiency of evidence information retrieval: five literature reviews and a
      qualitative study.
AB  - BACKGROUND: Effective study identification is essential for conducting health
      research, developing clinical guidance and health policy and supporting health
      care decision-making. Methodological search filters (combinations of search terms
      to capture a specific study design) can assist in searching to achieve this.
      OBJECTIVES: This project investigated the methods used to assess the performance
      of methodological search filters, the information that searchers require when
      choosing search filters and how that information could be better provided.
      METHODS: Five literature reviews were undertaken in 2010/11: search filter
      development and testing; comparison of search filters; decision-making in
      choosing search filters; diagnostic test accuracy (DTA) study methods; and
      decision-making in choosing diagnostic tests. We conducted interviews and a
      questionnaire with experienced searchers to learn what information assists in the
      choice of search filters and how filters are used. These investigations informed
      the development of various approaches to gathering and reporting search filter
      performance data. We acknowledge that there has been a regrettable delay between
      carrying out the project, including the searches, and the publication of this
      report, because of serious illness of the principal investigator. RESULTS: The
      development of filters most frequently involved using a reference standard
      derived from hand-searching journals. Most filters were validated internally
      only. Reporting of methods was generally poor. Sensitivity, precision and
      specificity were the most commonly reported performance measures and were
      presented in tables. Aspects of DTA study methods are applicable to search
      filters, particularly in the development of the reference standard. There is
      limited evidence on how clinicians choose between diagnostic tests. No published
      literature was found on how searchers select filters. Interviewing and
      questioning searchers via a questionnaire found that filters were not appropriate
      for all tasks but were predominantly used to reduce large numbers of retrieved
      records and to introduce focus. The Inter Technology Appraisal Support
      Collaboration (InterTASC) Information Specialists' Sub-Group (ISSG) Search
      Filters Resource was most frequently mentioned by both groups as the resource
      consulted to select a filter. Randomised controlled trial (RCT) and systematic
      review filters, in particular the Cochrane RCT and the McMaster Hedges filters,
      were most frequently mentioned. The majority indicated that they used different
      filters depending on the requirement for sensitivity or precision. Over half of
      the respondents used the filters available in databases. Interviewees used
      various approaches when using and adapting search filters. Respondents suggested
      that the main factors that would make choosing a filter easier were the
      availability of critical appraisals and more detailed performance information.
      Provenance and having the filter available in a central storage location were
      also important. LIMITATIONS: The questionnaire could have been shorter and could
      have included more multiple choice questions, and the reviews of filter
      performance focused on only four study designs. CONCLUSIONS: Search filter
      studies should use a representative reference standard and explicitly report
      methods and results. Performance measures should be presented systematically and
      clearly. Searchers find filters useful in certain circumstances but expressed a
      need for more user-friendly performance information to aid filter choice. We
      suggest approaches to use, adapt and report search filter performance. Future
      work could include research around search filters and performance measures for
      study designs not addressed here, exploration of alternative methods of
      displaying performance results and numerical synthesis of performance comparison
      results. FUNDING: The National Institute for Health Research (NIHR) Health
      Technology Assessment programme and Medical Research Council-NIHR Methodology
      Research Programme (grant number G0901496).

PMID- 29188765
TI  - Cross-linked guar gum and sodium borate based microspheres as colon-targeted
      anticancer drug delivery systems for 5-fluorouracil.
AB  - The aim was to prepare cross linked polymer of 5-fluorouracil loaded microspheres
      containing guar gum and sodium borate for colon-targeted drug delivery systems.
      Micro spheres were prepared using emulsification cross linking method. The
      influence of drug polymer ratio, cross linker agent concentrations and cross
      linking timing on in vitro drug release and characteristics in terms of drug
      loading, entrapment efficiency and yielding percentage were investigated. The
      optimum drug loading, entrapment efficiency and percent yield were obtained from
      formulations with the lowest content of cross linker agent over 2 h of cross
      linking timing but with the highest drug to polymer ratio 1:11. The optimum in
      vitro drug release was obvious upon decreasing drug to polymer ratio up to 1:09,
      resulting in 81.5% drug release over 24 h. In conclusion, micro spheres composed
      of gaur gum and sodium borate can delay and control the release of 5-fluorouracil
      over 24 h. Thus, further in vivo studies are suggested for final assessment.

PMID- 29188766
TI  - Larvicidal, pupicidal and adulticidal activities of non-polar solvent extract of
      Cymbopogon nardus (Linn.) whole plant against a mosquito, Culex quinquefasciatus
      (Say.).
AB  - The present research is aimed to investigate the susceptibility of Cx.
      quinquefasciatus larvae (2nd and 4th instars), pupae and adults during exposure
      to various concentrations of C. nardus n-hexane extract. Increase in mortality of
      larvae and pupae was observed with increase in concentration of the extract
      solution (R2>0.90). LC50 values of extract for 2nd and 4th instar larvae were
      451.8 and 599.6 ppm, respectively. The LC<inf>90</inf> values of extract for 2nd
      and 4th instar larvae were 2519.6 and 3017.7 ppm, respectively. The
      LC<inf>50</inf> and LC<inf>90</inf> values of extract during pupicidal activity
      were 1307.7 and 2257.9 ppm, respectively. During CDC bottle bioassay, mosquito
      adult knockdown was observed after exposure to various concentrations (0.15% to
      1.25%) of C. nardus n-hexane extract. The KDT<inf>50</inf> values at highest
      (1.25%) and lowest (0.15%) concentrations were 100.9 and 184.2 minutes,
      respectively. After 24 hours exposure period, the highest extract concentration
      (1.25%) caused 62.5+/-6.5% mortality. During filter paper impregnation bioassay,
      the KDT<inf>50</inf> value at highest concentration (0.13 mg/cm2) was 94.4
      minutes and at lowest concentration (0.017 mg/cm<sup>2</sup>) was 178.9 minutes.
      KDT90 values at these concentrations were 176.7 and 290.1 minutes, respectively.
      After 24 hours of recovery period, the filter papers impregnated with highest
      extract concentration (0.13mg/cm2) caused 60+/-8.2% mortality.

PMID- 29188767
TI  - Development and validation of stability indicating assay method for cinitapride
      in bulk & tablets.
AB  - A simple stability indicating UV-spectrophotometric method has been developed and
      validated for the determination of cinitapride hydrogen tartrate (CHT) in bulk
      and solid pharmaceutical dosage form. Drug absorption was measured in different
      analytical mediums however; maximum absorption was seen in 0.1 N HCl at
      wavelength (lambdamax) of 266 nm. The calibration curve was found to be linear
      over the concentration range from 6 to14MUg/mL with the correlation coefficient
      value (r) of 0.999. The LOD and LOQ were estimated to be 0.1019MUg/mL and
      0.309MUg/mL respectively. The accuracy was evaluated by determining the percent
      drug recovery, performed at three different levels of 50%, 100% and 150%. The%
      recovery was found to be in the range of 99.96-100.64%. The precision of the
      method was determined by inter-day and intra-day variations. The % RSD value <0.5
      indicates the underlying method is precise and accurate as well. The developed
      method was applied to characterize in vitro assay content of few brands of
      cinitapride (1 mg) available in local market. No interference of the formulation
      excipients with the drug absorption was observed during assay. Drug substance and
      drug product were exposed to various stressed conditions (acid, base, oxidative,
      thermal and photolysis). Forced degradation testing of drug product showed that
      the oxidation (20%) was found to be the major degradation pathway of the
      cinitapride. However; drug estimation was not influenced in presence of
      degradation moieties formed during acid, base, oxidation, thermal and photolytic
      breakdown. Overall, the investigated technique is robust and specific that would
      be successfully used to quantify the cinitapride hydrogen tartarate in
      pharmaceutical dosage and bulk form in future.

PMID- 29188768
TI  - Radiolabeling of benzylpenicillin with lutetium-177: Quality control and
      biodistribution study to develop theranostic infection imaging agent.
AB  - Benzylpenicillin acts through binding with beta-lactamase enzyme and inhibiting
      the bacterial cell wall biosynthesis. Therefore, the radiolabeling of
      benzylpenicillin with lutetium-177 is expected to serve as a theranostic agent
      for deep-seated bacterial infections. The radiolabeling of benzylpenicillin
      resulted ~93% radiochemical yield at optimized reaction conditions. Radiochemical
      purity analysis was tested with the help of Whatman No. 2 paper and instant thin
      layer chromatography. Biodistribution study with healthy New Zeeland white rabbit
      revealed moderate accumulation in different organs. Kidneys are the major organs,
      showed not more than 4.57+/-0.89% injected dose per gram organ (ID/gm organ) at 1
      h time point and 3.48+/-1.11% ID/gm organ at 6 h time point. The accumulation of
      tracer agent in liver was found in the range of 7.42+/-2.42% to 9.09+/-2.76 ID/gm
      organ. The glomerular filtration rate studies revealed rapid clearance - omitting
      the chance of nephrotoxicity. The radiolabeling yield, biodistribution and
      glomerular filtration rate results revealed <sup>177</sup>Lu-benzylpencillin
      could be a potential candidate to diagnose the deep-seated bacterial infection.

PMID- 29188769
TI  - Chromatographic method development and validation for the determination of
      valsartan in biological fluid.
AB  - A swift, precise and simple HPLC bioanalytical technique with UV detection was
      established and validated for quantitative estimation of valsartan in human
      plasma. The analyte was separated from plasma by protein precipitation with
      acetonitrile and chromatographically separated on Zorbax SB-C18 (5MUm, 4.6mm *
      15cm) column. The solvent mixture system consisting of acetonitrile, water and
      glacial acetic acid (40:59:1 v/v), was pumped using isocratic mode at 1mL/min
      flow rate. Samples' detection of drug was made spectrophotometrically at a
      wavelength of 264nm. The analyte response was instituted to be linear from 0.06
      to 8MUg/mL with a regression value of 0.999. The accuracy of the proposed method
      was ranged between 97.2-100.3% with 5% RSD. The analytical recovery (>95%) was
      consistently observed and satisfactory sample stability was also found at
      different environmental conditions. In conclusion the reported bio-analytical
      method is easy and robust that was successfully utilized in estimation of
      valsartan in a pharmacokinetic study.

PMID- 29188770
TI  - The hepatoprotective effects of aquatic extract of Levisticum officinale against
      paraquat hepatocyte toxicity.
AB  - Paraquat is extensively used as a strong nitrogen-based herbicide for controlling
      weeds in agriculture. This herbicide is extremely toxic to humans and induces
      multiorgan failure due to accumulation in the cells. So far, many instances of
      fatal poisoning have been reported. Paraquat is metabolized primarily in the
      liver. Accordingly, the effects of aquatic Levisticum officinale extract on
      biochemical factors and oxidative status were evaluated in hepatocytes exposed to
      paraquat in this study. The results showed that paraquat-induced hepatocyte
      destruction is mediated by reactive oxygen species (ROS) production. The aquatic
      extracts of Levisticum officinale (100, 200, and 300MUg/mL) could prevent lipid
      peroxidation and reduction in the potential of mitochondrial membranes (P<0.05).
      The antioxidants, ROS scavengers (mannitol, dimethyl sulfoxide, and alpha
      tocopherol), and mitochondrial permeability transition pore-sealing agent
      (carnitine) inhibited the effects of paraquat. The pore-sealing compound
      inhibited hepatotoxicity, indicating that paraquat induces cell death via
      mitochondrial pathways. Hepatic cell death due to paraquat could be prevented by
      hepatocyte pretreatment with aquatic Levisticum officinale extracts,
      antioxidants, and ROS scavengers; therefore, oxidative stress might directly
      reduce the mitochondrial membrane potential. In conclusion, paraquat
      hepatotoxicity may be associated with oxidative stress and maintained by the
      disruption of mitochondrial membrane potential. Levisticum officinale aquatic
      extract, presumably due to its strong antioxidant properties, could protect
      against the destructive effects of paraquat on rat hepatocytes.

PMID- 29188771
TI  - HPLC and GC-MS: Identification and Quantification of Strychnine and Brucine in
      Strychnos nux-vomica leaves.
AB  - In this study, we have aimed to analyze the phytochemical composition of this
      plant and the concentration of strychnine and brucine. The identification of
      bioactive compounds was done by GC-MS with NIST Library. Strychnine and Brucine
      were quantified using HPLC. Twenty one medicinal bio active compounds were
      identified from the Strychnos nux-vomica leaf ethanolic extract. Strychnine is
      showing 28.43% purity and brucine was not detected in GCMS analysis. Quantified
      the concentration of strychnine (0.6 mg in 500mg of extract) and brucine (1.6 mg
      in 500mg of extract) was done by HPLC against Strychnine and Brucine standard.
      These compounds are having natural properties of Anti-inflammatory,
      Hypocholesterole, Cancer preventive, Hepatoprotective, Antimicrobial,
      Antioxidant, Cardio protective, Antiaging, Antialzheimeran, Antidermatitic,
      Immunostimulant, Anthepatotoxic, biosynthesis of steroid hormones, Nematicide,
      Antiandrogenic, 5-alpha reductase inhibitor, antipsychotic, analgesic, apoptotic
      effect, antidepressant, antidote for snake poisoning and diabetic activity.

PMID- 29188772
TI  - Enriched environment palliates nicotine-induced addiction and associated
      neurobehavioral deficits in rats.
AB  - This study was designed to investigate the role of enriched environment in
      preventing and/or reducing the neurobehavioral deficits produced after nicotine
      administration in albino Wistar rats. Equal numbers of rat in two groups were
      either placed in social environment (control group) or social along with
      physically enriched environment for four weeks before the administration of
      nicotine. Exposure to different environmental conditions was followed by the
      intraperitoneal injection of nicotine at the dose of 0.6 mg/kg for seven
      consecutive days during which addictive behavior was monitored using conditioned
      placed preference paradigm. Behavioral responses to locomotor activity, anxiety
      and retention of short term memory were investigated in control and nicotine
      injected groups exposed to different environments. Results of this study showed
      that the rats pre-exposed to physical along with social enrichment exhibited a
      decrease in drug seeking behavior, hyper locomotion, anxiogenic effects along
      with improvement of working memory as compared to control and nicotine injected
      groups that were kept in social environment alone. This behavioral study suggests
      that the exposure to physical enrichment along with socialization in young age
      can later reduce the chances of compulsive dependence on nicotine and related
      neurobehavioral deficits.

PMID- 29188773
TI  - Sorafenib tosylate, Ribavirn and Sofosbuvir combination therapy for HCV virus
      infected patients with decompensated liver cancer.
AB  - Hepatitis C is the most common health problem worldwide and is major cause of
      death due to proliferation of hepatocellular carcinoma. The medicines available
      for HCV treatment overcome up-to 95% complications of HCV. However, liver cancer
      needs some additional care. Normally Sorafenib tosylate 200 mg is recommended for
      liver cancer. There is no such trial in which this drug could effectively be used
      in combination of direct acting antivirals for HCV. The study was conducted for
      HCV patients (n=30) with liver cancer having decompensated stage. Combination of
      Sorafenib tosylate, Ribavirn and Sofosbuvir were used for the pharmacokinetics of
      these medicines. Child pugh score less then 7 (CP A) in adults during treatment
      phase (received 12 weeks of Sorafenib tosylate 200 mg, Ribavirn and Sofosbuvir
      400 mg once daily) have no side effect while child pugh score 7-9 (CP B) have
      evidence of hypertension. The main efficiency end point sustained virology
      response with overcoming liver cancer as well in 12 weeks after end treatment
      (SVR-LLC 12). Mean pharmacokinetic exposure to Sorafenib tosylate 200 mg,
      Ribavirn and Sofosbuvir at week 8th was 2.1, 1.5,1.2 times greater in CP B than
      in CP A. Adverse effects (AEs) were observed in 12 out of 30 patients but not
      severe as lethal for life. Treatment with Sorafenib tosylate, Ribavirn and
      Sofosbuvir for twelve weeks was harmless and well accepted, 100 % patients
      achieve (SVR LLC 12) with 10-fold cure rate more than previous ones. The
      combination therapy of Sorafenib tosylate, Ribavirn and Sofosbuvir was found
      helpful for the management of decompensated liver cancer.

PMID- 29188774
TI  - Biologically active compounds from the red sea sponge Suberea sp.
AB  - Investigation of the cytotoxic fraction of the extracts of the Red Sea sponge
      Suberea sp. resulted in the identification of two new compounds, 1-(hydroxy(1H
      pyrrol-2-yl)methyl)guanidine and 4-(2-amino-3-methylbut-3-en-1-yl)phenol (1 and
      2) together with the previously reported 2-(3,5-dibromo-4-hydroxyphenyl)acetamide
      (3), subereaphenol C (4), dibromoverongiaquinol (5) and bromochloroverongiaquinol
      (6). The compounds were assigned by assignment of their one- and two-dimensional
      NMR and MS spectral data. The cytotoxic activities of the compounds against two
      cancer cell lines were evaluated. In addition, the antimicrobial activities of
      the compounds was discussed.

PMID- 29188775
TI  - Isolation and characterization of antibiotic producing bacterial strains from red
      soil of Himalayan region of Pakistan.
AB  - The emergence of multi drug resistant microbial pathogens has become a global
      health challenge and set a dire requirement of searching new effective
      antimicrobials. Soil is an ultimate reservoir of biologically active micro flora,
      which harbors trillions of microbial strains producing compounds of commercial
      interest. Hence aim of the present study was an attempt to isolate and identify
      the antibiotic producing microbial strains from the red soil of Himalayan an
      unexplored region of Pakistan. In this study from 10 different soil samples only
      one bacterial strain was isolated capable of antimicrobial activity. Strain was
      identified by biochemical characteristics and final identification was done by
      API 20 NE kit which showed 99% homology with P. aeruginosa. Hence the strain was
      identified as P. aeruginosa S2. Antibacterial and antifungal activity of the P.
      aeruginosa S2 showed that Staphylococcus aureus was extremely sensitive to it
      with a zone of inhibition of 42mm. Staphylococcus epidermidis, Enterobacter
      aerogenes, Aspergillus fumigatus and Candida albicans were also inhibited by the
      isolated strain. Effect of Glycerol, Copper sulphate (CuSo4), Sodium sulphate
      (Na2SO4) and Glycerol on antibiotic production was also evaluated by
      supplementing growth media with these chemicals. Pseudomonas aeruginosa was grown
      in bulk quantity using solid state fermentation and crude extract was prepared
      using organic solvents and subjected to silica gel column chromatography for
      purification of active compound. Purified compound showed antibacterial against
      human pathogens. The unexplored Kashmir Himalayas are of great significance
      because of its richness in biodiversity and need to be explored for isolation and
      characterization of native microbes for biologically active secondary
      metabolites. This untouched region may be considered as hub of new antimicrobials
      and may have applications in natural product-based drug discovery.

PMID- 29188776
TI  - Metal complexes of isonicotinylhydrazide and their antitubercular activity.
AB  - The development and spreading of Multi Drug Resistant TB strains is hampering
      endeavours for the control and administration of tuberculosis (TB). The expansion
      episodes of multi-medication safe strains of Mycobacterium tuberculosis against
      first and second line antituberculosis drugs on one side and the unfavourable
      effects of these drugs on the other side has led the enthusiasm of researcher
      towards the synthesis of metal complexes of various medication. This approach is
      born with the expectation of finding new antituberculous operators without or
      least reactions as well as being active against the resistant strains of
      Mycobacterium tuberculosis. This study concentrates on the screening of five
      metal complexes of isoniazid (INH) against five Mycobacterium tuberculosis
      strains. These strains have been confirmed by WHO being active and even
      proliferating safely even in the presence of pyrazinamide, isoniazid (INH),
      ethambutol and rifampicin. In this work INH was taken as reference medication.
      All synthesized complexes and INH were subjected for a month and a half in BACTEC
      MGIT 960 technique. INH and its Fe (II) complex restrained the development of all
      bacterial strains for merely two weeks, while the Fe(III), Cu(II), Co (II) and Mn
      (II) complexes repressed the development five strains for three weeks.
      Conclusively, the strains utilized in this study were discovered to be more
      susceptible to the later four complexes than the ligand (INH) drug and its Fe
      (II) complex. Furthermore, elemental analysis and atomic absorption of all
      complexes were conducted for the determination of metal to ligand ratio.

PMID- 29188777
TI  - The role of Glutathione, Cysteine and D-Penicillamine in exchanging Palladium and
      Vanadium metals from albumin metal complex.
AB  - Thiol groups are extensively present across biological systems being found in
      range of small molecules (e.g. Glutathione, Homo-cysteine) and proteins (e.g.
      albumin, haemo-globin). Albumin is considered to be a major thiol containing
      protein present in circulating Plasma. Albumin contains a single thiolate group
      located at cysteine-34(cys-34) at its active site. Albumin also binds a wide
      variety of metals and metals complexes at various sites around the protein.
      Usually heavy metals are preferentially attached with the thiol group of albumin.
      The binding of heavy metals at cys-34 provides a mechanism by which the residence
      time of potentially toxic species in the body can be increased. In this research
      we have assessed the oxidative modification of and metal binding capacity of cys
      34 with heavy metals Palladium and Vanadium to investigate the ease with which it
      is possible to effect disulfide-thiol exchange at this sites/or remove a metal
      bound at this position. Both the metals were treated with albumin and then the
      albumin metals (Pd and V) complexes were treated with small thoil molecules like
      Glutathione, Cysteine and D-Penicillamine. Our finding showed that the albumin
      thiol group retained the metals with itself by forming some strong bonding with
      the Thiols group, it is concluded from this finding that if by chance both the
      metals enter the living system; strongly disturb the chemistry and physiological
      function of this bio-molecule.

PMID- 29188778
TI  - Cytotoxic and acute toxicity studies of isoniazid derivatives.
AB  - Cancer is ultimately the result of cells that hysterically grow and do not die.
      Cells can experience uncontrolled growth if there are mutations to DNA, and
      therefore, alterations to the genes involved in cell division. Cancer occurs when
      a cell's gene mutations make the cell unable to correct DNA damage and is unable
      to destroy itself. There are over 100 different types of cancer each classified
      by the type of initially affected cell. Isoniazid, a well-known antitubercular
      agent has been reported to exhibit some cytotoxic activity. This finding prompt
      us to carry out this study where isoniazid and its sixteen derivatives were
      studied for any possible cytotoxic activity against Human astrocytoma SNB-19
      cells, human Dukes' type C colorectal adenocarcinoma HCT-15 cells, human Dukes'
      type D colorectal adenocarcinoma COLO-205 cells, and human prostate
      adenocarcinoma (grade IV) PC-3 cells. Among the test compounds, SN-07 (a phenacyl
      derivative with para phenyl substitution) demonstrated slight cytotoxic effects
      on two types of human colorectal adenocarcinoma cells HCT-15 and COLO-205.
      Moreover, the acute toxicity of the compounds was also estimated in which some
      compounds were evaluated with more LD50 values than isoniazid.

PMID- 29188779
TI  - MRSA: Prevalence and susceptibility pattern in health care setups of Karachi.
AB  - This assessment aims to determine the prevalence of methicillin resistance and
      multidrug resistance (MDR) among the clinical isolates of Staphylococcus aureus
      and antimicrobial susceptibility profile of methicillin resistant Staphylococcus
      aureus (MRSA) to the frequently prescribed antibiotics in Karachi. Isolates of
      MRSA, recovered from various clinical samples were included in this prospective,
      cross-sectional study from Jan 2015 to June 2017. Agar diffusion method was
      employed according to the protocols of Clinical Laboratory Standards Institute.
      Out of total 346 S. aureus strains, the frequency rate of MRSA was 52% (n = 180).
      MRSA infection was found higher among the age group 21-30 years i.e. 30% (n=54),
      followed by 20% (n=36) in 31-40 years. Frequency of MRSA percentage in male and
      female was and 70% and 30% respectively. MRSA was more frequently observed in
      blood 20% (n=36). MRSA showed high resistance (100%) to Oxacillin and Cefoxitin
      while 25% Vancomycin resistant S. aureus (VRSA) isolates and 25% Teicoplanin
      resistance were also reported. MRSA exhibited 16% resistance to Minocycline. It
      was concluded that MRSA pose a challenging threat to public health in Karachi. In
      addition, MDR should be periodically checked to avoid treatment failure.

PMID- 29188780
TI  - Dizocilpine induced psychosis-like behavior in rats: A possible animal model with
      full spectrum of schizophrenia.
AB  - Schizophrenia (SZ) is categorized as neuropsychiatric disorder with reduced
      lifespan and significant impairments in social and vocational functioning. One of
      the best proposed pharmacological animal models is dizocilpine, as it can mimic
      the full spectrum of schizophrenic disorder including positive and negative
      symptoms along with cognitive deficits. Dizocilpine is N-methyl-D-aspartate
      (NMDA) receptor antagonist known to induce hyper-locomotion and stereotyped
      behavior in rodents. Present study was designed to develop an animal model of SZ
      via intraperitoneal administration of dizocilpine in rats (100-150g) at a dose of
      0.3 mg/kg for eight days. For the evaluation of positive symptoms, hyperlocomotor
      behavior was monitored. Negative symptoms were assessed by sucrose preference
      test (SPT) and social interaction test (SIT). Moreover, Cognitive deficits were
      evaluated by novel object recognition test (NORT). After behavioral assessments
      animals were decapitated for further evaluation of biochemical and neurochemical
      estimations. Present findings revealed that dizocilpine injected rats exhibited
      significant hyperlocomotor behavior, depressive symptoms and cognitive deficits.
      Results are further strengthened with a marked increase in lipid per oxidation
      (LPO) in brain and a decline in reduced glutathione (GSH) levels. Biogenic amine
      levels (Dopamine, DA; 5-hydroxytryptamine, 5-HT) were also significantly
      increased and decreased respectively. Thus, present findings suggest that
      dizocilpine can be used as one of the best drug to develop psychosis-like
      symptoms in rats and to develop an animal model following a short-term study.

PMID- 29188781
TI  - Notch1 signaling activation protected myocardium against hypoxia injury via
      reducing programmed cell death.
AB  - Programmed cell death plays an important role in cardio protection, and Notch1
      was an important factor related to programmed cell death. The role of Notch1 on
      ischemia myocardium remains unclear.H9C2 myocardial cells were cultured with
      routine medium, transfected with Notch1 over expression plasmid, Notch1-siRNA
      overexpression plasmid and vehicle plasmid for further hypoxic experiment.
      Condition of hypoxic experiment was 1% oxygen centration and culturing for
      12hours, then the cell proliferation activity and apoptosis rate was assessed by
      MTS kit and flow cytometry, respectively. The expressions of Caspase-3, Caspase-9
      and Bcl-2 were determined by RT-qPCR and Western Blot, respectively. Compared
      with normoxia treatment, hypoxia could decrease H9C2 cell proliferation activity
      as well as Bcl-2 mRNA expression, and increase cell apoptosis rate as well as
      Caspase-3 and Caspase-9 mRNA expression. Notch1 activation could increase
      proliferation activity as well as Bcl-2 mRNA expression, while decrease apoptosis
      rate as well as Caspase-3 and Caspase-9 mRNA expression. Compared with Notch1
      activation H9C2 cells, the opposite effect on programmed cell death was observed
      in cells with Notch1-siRNA-overexpression plasmid. Targeted activation of Notch1
      gene to reduce hypoxia-induced programmed cell death in myocardial cells via up
      regulating the expression of Caspase-3 and Caspase-9 and inhibiting the
      expression of Bcl-2.

PMID- 29188782
TI  - Pharmacokinetic behavior of montelukast in indigenous healthy male volunteers.
AB  - Aim of present study was to investigate the pharmacokinetic behavior of
      Montelukast in the healthy male volunteers under indigenous conditions. One
      tablet of montelukast 10 mg was administered in each subject and blood at
      different time intervals. Concentration of montelukast in plasma samples was
      analyzed by high performance liquid chromatography method to calculate
      pharmacokinetic parameters. The plasma concentration of montelukast was in the
      range of 1.31-1.76MUg/mL at 0.5-12 hours with Cmax value of 1.59+/-0.16MUg/mL at
      3.71+/-0.64 hours. These values of plasma drug concentrations were above the
      minimum effective concentration of montelukast during the entire study hours.
      Absorption and elimination half-lives of the montelukast were evaluated as 2.52+/
      0.54 hours and 2.63+/-0.35 hours, respectively. The volume of distribution and
      total body clearance of montelukast were investigated as 0.34+/-0.01 L/kg and
      0.01+/-0.00 L/hr/kg, respectively. The pharmacokinetic parameters i.e. Cmax, AUC,
      t1/2, Vd and ClB of montelukast calculated in present study were found different
      as compared to that of the previous literature values which was due to genetic
      and environmental variation.

PMID- 29188784
TI  - [New concerns in digital age].

PMID- 29188783
TI  - The Recent Emergence of Clostridium difficile Infection in Romanian Hospitals is
      Associated with a High Prevalence of Polymerase Chain Reaction Ribotype 027.
AB  - AIMS: To investigate the epidemiology of Clostridium difficile infection in
      Romanian hospitals. METHODS: A survey was conducted at nine hospitals throughout
      Romania between November 2013 and February 2014. RESULTS: The survey identified
      393 patients with Clostridium difficile infection. The median age was 67 years
      (range: 2-94 years); 56% of patients were aged >65 years. The mean prevalence of
      Clostridium difficile infection was 5.2 cases per 10.000 patient-days. The
      highest prevalences were 24.9 and 20 per 10.000 patient-days in hospitals
      specializing in gastroenterology and infectious diseases, respectively.
      Clostridium difficile infections were health care-associated in 70.5% patients
      and community-acquired in 10.2%. The origin was not determined in 19.3%.
      Clostridium difficile infection was severe in 12.3% of patients, and the in
      hospital all-cause mortality was 8.8%. Polymerase chain reaction ribotype 027 had
      the highest prevalence in all participating hospitals and represented 82.6% of
      the total ribotyped isolates. The minimum inhibitory concentration of
      moxifloxacin was >4 MUg/mL for 59 of 80 tested isolates (73.8%). Of 59 isolates,
      54 were highly resistant to moxifloxacin (minimum inhibitory concentration >=32
      MUg/mL), and the majority were polymerase chain reaction ribotype 027 (p<0.0001).
      CONCLUSION: The ribotype 027 was the predominant cause of Clostridium difficile
      infections in Romania. In some specialized hospitals, the prevalence of
      Clostridium difficile infection was higher than the European mean prevalence, and
      this demonstrates the need for strict adherence to infection control programs.

PMID- 29188785
TI  - [Outcome after surgical resection for rectal cancer and its precursors in
      Landspitali University Hospital 2008-2012].
AB  - BACKGROUND: Rectal cancer makes up 2-3% of all cancers in Iceland and surgery is
      the mainstay of its treatment. Information regarding those who undergo resection
      of the rectum because of rectal cancer or its precursors in Iceland today is
      lacking. The aim of this study was to evaluate what kind of surgical treatment
      rectal cancer patients receive at Landspitali University Hospital along with peri
      operative and long-term outcomes. METHODS: The study was retrospective. All
      patients undergoing total or partial resection of the rectum for rectal cancer or
      its precursor from 2008-2012 in Landspitali University hospital were included.
      Information regarding age, sex, surgery, neoadjuvant and adjuvant treatment along
      with reoperations and survival were gathered. RESULTS: The total number of
      patients included were 144. Mean age was 66 years (33-89). Neoadjuvant treatment
      was used in 65 (45%) cases. Most of the patients (65%) underwent anterior
      resection of the rectum, 21% abdominoperineal resection, 11% Hartmann's procedure
      and 3% other surgery. Majority of the patients had a cancer diagnoses (88%) but
      12% had dysplastic adenomas. An anastomosis was made in 67% of cases, others
      (33%) got a permanent stoma. Reoperation rate within 30 days was 12%. Thirty day
      and 1 year mortality were 0.7% and 6.2% respectively. Average follow up time was
      56 months (1-98). Local recurrence rate was 7,1%, five year survival rate was
      77%. CONCLUSION: The surgical treatment for rectal cancer in Landspitali is up to
      international standard. Perioperative and long-term outcomes are similar to what
      other authors have reported.

PMID- 29188786
TI  - [The diversion of prescribed stimulant medications of 10th graders in Iceland].
AB  - INTRODUCTION: ADHD is a neurodevelopmental disorder that usually surfaces before
      seven years of age. Stimulants are commonly used medications for the treatment of
      this disorder in Iceland, but they carry with them a significant risk of both
      abuse and diversion - i.e. when it is used by an individual other than it was
      prescribed for by a physician. The purpose of this study was to estimate the
      prevalence of diversion amongst Icelandic adolescents. MATERIAL AND METHODS: This
      study is based on data collected in the Icelandic portion of the European School
      Survey Project on Alcohol and Other Drugs (ESPAD) focused on the drug and alcohol
      use of 10th graders in Europe. RESULTS: Of the 2,306 students that participated
      in the study 91% (2,098) claimed they had never been prescribed stimulant
      medications while 9% (208) claimed they had. Boys were twice as likely to get a
      stimulant prescription compared to girls. Almost 18% of the participants that had
      been prescribed simulants said they had at some point in time diverted their
      stimulant medication. CONCLUSION: The diversion of stimulants by 10th graders in
      Iceland is quite common compared to studies from other countries where the
      prevalence is closer to 5-10%. These findings demonstrate the importance of
      carefully overseeing stimulant use of adolescents, for the benefit of both those
      who divert as well as those diverted to.

PMID- 29188787
TI  - [Medical practice, magic and religion - conjunction and development before and
      after Reformation].
AB  - The conjunction between medical practice, religion and magic becomes rather
      visible when one peers into old scripts and ancient literature. Before the
      foundation and diffusion of universities of the continent, the european convents
      and cloisters were the centers of medical knowl-edge and -practice for centuries.
      Alongside the scholarly development of medical science, driven from the roots of
      the eldest scholarly medicial practice, the practice of folk-medicin flourished
      and thrived all over Europe, not least the herbal-medicine which is the original
      form and foundation for modern pharmacy. This article deals with the conjunction
      of religion, magic and medical practice in ancient Icelandic sources such as the
      Old-Norse literature, medical-scripts from the 12th - 15th century Iceland, and
      not least the Icelandic magical-scripts (galdrakver) of the 17th century. The
      last mentioned documents were used as evidence in several witch-trials that led
      convicted witches to suffer executions at the stake once the wave of European
      witch-persecutions had rushed ashore in 17th century Iceland. These sources
      indicate a decline of medical knowledge and science in the 16th and 17th century
      Iceland, the medical practice being rather undeveloped at the time - in Iceland
      as in other parts of Europe - there-fore a rather unclear margin between "the
      learned and the laymen". While common people and folk-healers were convicted as
      witches to suffer at the stake for possession of magical scripts and healing
      books, some scholars of the state of Danmark were practicing healing-methods that
      deserve to be compared to the activities of the former ones. That comparison
      raises an inevitable question of where to draw the line between the learned
      medical man and the magician of 17th century Iceland, that is between Magic and
      Science.

PMID- 29188789
TI  - From Mn3O4/MnO core-shell nanoparticles to hollow MnO: evolution of magnetic
      properties.
AB  - Manganese oxide nanoparticles (MNOPs), when dispersed in a water solution, show a
      magnetic behavior that drastically changes after an aging process. In this paper,
      the variation in the magnetic properties has been correlated with the structural
      evolution of the nanoparticles: in particular, the as prepared Mn3O4/MnO
      core/shell system manifests a low temperature magnetization reversal that is
      strongly affected by the presence of the MnO shell and, in particular, by the
      existence of a frustrated interfacial region playing a key role in determining
      the low temperature irreversibility, the finite coercivity slightly above the
      Curie temperature of the Mn3O4 phase and the horizontal displacement of the FC
      hysteresis loop. On the other hand, the magnetic behavior of the aged system
      results dominated by the presence of Mn3O4 whose highly anisotropic character
      (i.e. high coercivity and high magnetization remanence) is attributed to the
      presence of a large fraction of surface spins. Such a result is consistent with
      the structural evolution, from core/shell to hollow nanoparticles, as shown by
      TEM observation.

PMID- 29188790
TI  - IRPA Consultation: is the system of protection 'fit for purpose' and can it be
      readily communicated? Views of the radiation protection professionals.
AB  - The system of protection, which provides the basic underpinning philosophy and
      principles for radiation protection, is constantly evolving in the light of
      developing scientific understanding and practical experience. Over recent times
      there has been significant learning from experiences relating to the Fukushima
      accident, and there is also increasing recognition of the importance of enhancing
      public understanding of radiation and risk. The practical application of
      radiation protection is undertaken by thousands of practitioners around the
      world, and it is IRPA's task to ensure that this experience is fed back for the
      benefit of all. This Memorandum reports the outcome of IRPA's consultation on the
      system of protection. The principal issues raised in the consultation include
      general perceptions of the system, risk uncertainties at low dose, the context of
      natural background exposure, dose limits and limitation, ALARA and
      reasonableness, and public understanding and communication of radiation and risk.

PMID- 29188788
TI  - Mechanistic insights of the Min oscillator via cell-free reconstitution and
      imaging.
AB  - The MinD and MinE proteins of Escherichia coli self-organize into a standing-wave
      oscillator on the membrane to help align division at mid-cell. When unleashed
      from cellular confines, MinD and MinE form a spectrum of patterns on artificial
      bilayers-static amoebas, traveling waves, traveling mushrooms, and bursts with
      standing-wave dynamics. We recently focused our cell-free studies on bursts
      because their dynamics recapitulate many features of Min oscillation observed in
      vivo. The data unveiled a patterning mechanism largely governed by MinE
      regulation of MinD interaction with membrane. We proposed that the MinD to MinE
      ratio on the membrane acts as a toggle switch between MinE-stimulated recruitment
      and release of MinD from the membrane. In this review, we summarize cell-free
      data on the Min system and expand upon a molecular mechanism that provides a
      biochemical explanation as to how these two 'simple' proteins can form the
      remarkable spectrum of patterns.

PMID- 29188791
TI  - Block matching sparsity regularization-based image reconstruction for incomplete
      projection data in computed tomography.
AB  - In medical imaging many conventional regularization methods, such as total
      variation or total generalized variation, impose strong prior assumptions which
      can only account for very limited classes of images. A more reasonable sparse
      representation frame for images is still badly needed. Visually understandable
      images contain meaningful patterns, and combinations or collections of these
      patterns can be utilized to form some sparse and redundant representations which
      promise to facilitate image reconstructions. In this work, we propose and study
      block matching sparsity regularization (BMSR) and devise an optimization program
      using BMSR for computed tomography (CT) image reconstruction for an incomplete
      projection set. The program is built as a constrained optimization, minimizing
      the L1-norm of the coefficients of the image in the transformed domain subject to
      data observation and positivity of the image itself. To solve the program
      efficiently, a practical method based on the proximal point algorithm is
      developed and analyzed. In order to accelerate the convergence rate, a practical
      strategy for tuning the BMSR parameter is proposed and applied. The experimental
      results for various settings, including real CT scanning, have verified the
      proposed reconstruction method showing promising capabilities over conventional
      regularization.

PMID- 29188792
TI  - Helical edge states in silicene and germanene nanorings in perpendicular magnetic
      field.
AB  - Due to nonzero intrinsic spin-orbit interaction in buckled honeycomb crystal
      structures, silicene and germanene exhibit interesting topological properties,
      and are therefore candidates for the realization of the quantum spin Hall effect.
      We employ the Kane-Mele model to investigate the electron states in hexagonal
      silicene and germanene nanorings having either zigzag or armchair edges in the
      presence of a perpendicular magnetic field. We present results for the energy
      spectra as function of magnetic field, the electron density of the spin-up and
      spin-down states in the ring plane, and the calculation of the probability
      current density. The quantum spin Hall phase is found at the edges between the
      nontrivial topological phase in silicene and germanene and vacuum. We demonstrate
      that the helical edge states in zigzag silicene and germanene nanorings can be
      qualitatively well understood by means of classical magnetic moments. However,
      this is not the case for comparable-sized armchair nanorings, where the
      eigenfunctions spread throughout the ring. Finally, we note that the energy
      spectra of silicene and germanene nanorings are similar and that the differences
      between the two are mainly related to the difference in magnitude of the spin
      orbit coupling.

PMID- 29188793
TI  - Special issue on ultrafast magnetism.

PMID- 29188795
TI  - Minority report: targeting emerging viruses before their emergence.

PMID- 29188797
TI  - Rabies.
AB  - Rabies is a life-threatening neglected tropical disease: tens of thousands of
      cases are reported annually in endemic countries (mainly in Africa and Asia),
      although the actual numbers are most likely underestimated. Rabies is a zoonotic
      disease that is caused by infection with viruses of the Lyssavirus genus, which
      are transmitted via the saliva of an infected animal. Dogs are the most important
      reservoir for rabies viruses, and dog bites account for >99% of human cases. The
      virus first infects peripheral motor neurons, and symptoms occur after the virus
      reaches the central nervous system. Once clinical disease develops, it is almost
      certainly fatal. Primary prevention involves dog vaccination campaigns to reduce
      the virus reservoir. If exposure occurs, timely post-exposure prophylaxis can
      prevent the progression to clinical disease and involves appropriate wound care,
      the administration of rabies immunoglobulin and vaccination. A multifaceted
      approach for human rabies eradication that involves government support, disease
      awareness, vaccination of at-risk human populations and, most importantly, dog
      rabies control is necessary to achieve the WHO goal of reducing the number of
      cases of dog-mediated human rabies to zero by 2030.

PMID- 29188796
TI  - In situ regeneration of retinal pigment epithelium by gene transfer of E2F2: a
      potential strategy for treatment of macular degenerations.
AB  - The retinal pigment epithelium (RPE) interacts closely with photoreceptors to
      maintain visual function. In degenerative diseases such as Stargardt disease and
      age-related macular degeneration, the leading cause of blindness in the developed
      world, RPE cell loss is followed by photoreceptor cell death. RPE cells can
      proliferate under certain conditions, suggesting an intrinsic regenerative
      potential, but so far this has not been utilised therapeutically. Here, we used
      E2F2 to induce RPE cell replication and thereby regeneration. In both young and
      old (2 and 18 month) wildtype mice, subretinal injection of non-integrating
      lentiviral vector expressing E2F2 resulted in 47% of examined RPE cells becoming
      BrdU positive. E2F2 induced an increase in RPE cell density of 17% compared with
      control vector-treated and 14% compared with untreated eyes. We also tested this
      approach in an inducible transgenic mouse model of RPE loss, generated through
      activation of diphtheria toxin-A gene. E2F2 expression resulted in a 10-fold
      increase in BrdU uptake and a 34% increase in central RPE cell density. Although
      in mice this localised rescue is insufficiently large to be demonstrable by
      electroretinography, a measure of massed retinal function, these results provide
      proof-of-concept for a strategy to induce in situ regeneration of RPE for the
      treatment of RPE degeneration.

PMID- 29188798
TI  - Capsaicin enhances the antitumor activity of sorafenib in hepatocellular
      carcinoma cells and mouse xenograft tumors through increased ERK signaling.
AB  - Sorafenib, a small inhibitor of tyrosine protein kinases, is currently the
      standard chemotherapy drug for the treatment of advanced hepatocellular carcinoma
      (HCC). Although sorafenib improves the survival of HCC patients, its efficacy is
      not optimal and requires further improvement. Capsaicin, the major active
      component of chili peppers from the genus Capsicum, is not only the agonist of
      TRPV1 channel, but also displays antitumor activity and enhances the sensitivity
      of cancer cells to cytotoxic drugs. In this study, we investigated the antitumor
      effects of combined sorafenib and capsaicin on HCC cells in vitro and xenograft
      tumors. Treatment with capsaicin alone dose-dependently inhibited the
      proliferation of the HCC cell lines PLC/PRF/7, HuH7 and HepG2 with IC50 values of
      137, 108 and 140.7 MUmol/L, respectively. No obvious expression of TRPV1 channel
      was detected in the 3 HCC cell lines and TRPV1 channel blockers did not alleviate
      the cytotoxicity of capsaicin. By contrast, combining capsaicin and sorafenib
      significantly enhanced the suppression on cell proliferation, achieving a high
      level synergistic effect (inhibition rates over 50%) and promoting HCC cell
      apoptosis. In nude mice with PLC/PRF/5 xenografts, combined administration of
      capsaicin and sorafenib significantly enhanced the suppression on tumor growth
      without apparent gross toxicity compared to either agent alone. Mechanistically,
      capsaicin (10-200 MUmol/L) dose-dependently increased the levels of
      phosphorylated ERK (p-ERK) in PLC/PRF/5 cells, thus leading to enhanced sorafenib
      sensitivity and a synergistic suppression on the tumor cells. Taken together, our
      results suggest that capsaicin-increased phosphorylation of ERK contributes to
      the enhanced antitumor activity of sorafenib, and capsaicin may be useful in
      improving the efficacy of sorafenib for the treatment of HCC.

PMID- 29188800
TI  - Chip-based digital PCR as a novel detection method for quantifying microRNAs in
      acute myocardial infarction patients.
AB  - miRNAs have shown promise as potential biomarkers for acute myocardial infarction
      (AMI). However, the current used quantitative real-time PCR (qRT-PCR) allows
      solely for relative expression of nucleic acids and it is susceptible to day-to
      day variability, which has limited the validity of using the miRNAs as
      biomarkers. In this study we explored the technical qualities and diagnostic
      potential of a new technique, chip-based digital PCR, in quantifying the miRNAs
      in patients with AMI and ischaemia-reperfusion injury (I/R). In a dilution series
      of synthetic C.elegans-miR-39, chip-based digital PCR displayed a lower
      coefficient of variation (8.9% vs 46.3%) and a lower limit of detection (0.2
      copies/MUL vs 1.1 copies/MUL) compared with qRT-PCR. In the serum collected from
      24 patients with ST-elevation myocardial infarction (STEMI) and 20 patients with
      stable coronary artery disease (CAD) patients after percutaneous coronary
      intervention (PCI), we used qRT-PCR and multiplexed chip-based digital PCR to
      quantify the serum levels of miRNA-21 and miRNA-499 as they have been validated
      in AMI in prior studies. In STEMI, I/R injury was assessed via measurement of ST
      segment resolution (ST-R). Chip-based digital PCR revealed a statistical
      significance in the difference of miR-21 levels between stable CAD and STEMI
      groups (118.8 copies/MUL vs 59 copies/MUL; P=0.0300), whereas qRT-PCR was unable
      to reach significance (136.4 copies/MUL vs 122.8 copies/MUL; P=0.2273). For miR
      499 levels, both chip-based digital PCR and qRT-PCR revealed statistically
      significant differences between stable CAD and STEMI groups (2 copies/MUL vs 8.5
      copies/MUL, P=0.0011; 0 copies/MUL vs 19.4 copies/MUL; P<0.0001). There was no
      association between miR-21/499 levels and ST-R post-PCI. Our results show that
      the chip-based digital PCR exhibits superior technical qualities and promises to
      be a superior method for quantifying miRNA levels in the circulation, which may
      become a more accurate and reproducible method for directly quantifying miRNAs,
      particularly for use in large multi-centre clinical trials.

PMID- 29188801
TI  - Pharmacokinetic and pharmacodynamic evidence for developing an oral formulation
      of octreotide against gastric mucosal injury.
AB  - Among the somatostatin analogues, octreotide (OCT) is the most commonly used in
      clinic via intravenous or subcutaneous injection to treat various diseases caused
      by increased secretion of growth hormone, gastrin or insulin. In order to assesse
      the feasibility of developing oral formulations of OCT, we conducted systematical
      pharmacokinetic and pharmacodynamic analyses of OCT in several animal models. The
      pharmacokinetic studies in rats showed that intragastric administration of OCT
      had extremely low bioavailability (<0.5%), but it could specifically distribute
      to the gastric mucosa due to the high expression of somatostatin receptor 2
      (SSTR2) in the rat stomach. The pharmacodynamic studies revealed that
      intragastric administration of OCT dose-dependently protected against gastric
      mucosal injury (GMI) in mice with WIRS-induced mouse gastric ulcers, which were
      comparable to those achieved by intravenous injection of OCT, and this effect was
      markedly attenuated by co-administration of CYN-154806, an antagonist of SSTR2.
      In pyloric ligation-induced ulcer mice, we further demonstrated that OCT
      significantly reduced the secretion of gastric acid via down-regulating the level
      of gastrin, which was responsible for the protective effect of OCT against GMI.
      Overall, we have provided pharmacokinetic and pharmacodynamic evidence for the
      feasibility of developing an oral formulation of OCT. Most importantly, the
      influence of SSTR2 on the pharmacokinetics and pharmacodynamics of OCT suggested
      that an oral formulation of OCT might be applicable for other clinical
      indications, including neuroendocrine neoplasms and pituitary adenoma due to the
      overexpression of SSTR2 on these tumor cells.

PMID- 29188799
TI  - Computational insights into the G-protein-biased activation and inactivation
      mechanisms of the MU opioid receptor.
AB  - The MU opioid receptor (OR), a member of the class A subfamily of G-protein
      coupled receptors (GPCRs), is a major target for the treatment of pain. G-protein
      biased MU-OR agonists promise to be developed as analgesics. Thus, TRV130, the
      first representative MU-OR ligand with G-protein bias, has entered into phase III
      clinical trials. To identify the detailed G-protein-biased activation and
      inactivation mechanisms of the MU-OR, we constructed five MU-OR systems that were
      in complexes with the G-protein-biased agonists TRV130 and BU72, the antagonists
      beta-FNA and naltrexone, as well as the free receptor. We performed a series of
      conventional molecular dynamics simulations and analyses of G-protein-biased
      activation and inactivation mechanisms of MU-OR. Our results, together with
      previously reported mutation results, revealed the operating mode of the
      activation switch composed of residues W6.48 and Y7.43 (Ballesteros/Weinstein
      numbering), the activity of which was responsible for down- and up-regulation,
      respectively, of the beta-arrestin signaling, which in turn affected G-protein
      biased activation of MU-OR. TRV130 was found to stabilize W6.48 by interacting
      with Y7.43. In addition, we obtained useful information regarding MU-OR-biased
      activation, such as strong stabilization of W7.35 through a hydrophobic ring
      interaction in the TRV130 system. These findings may facilitate understanding of
      MU-OR biased activation and the design of new biased ligands for GPCRs.

PMID- 29188804
TI  - Device therapy: Interatrial shunt device for HFpEF.

PMID- 29188802
TI  - The LPI/GPR55 axis enhances human breast cancer cell migration via HBXIP and p
      MLC signaling.
AB  - The G protein-coupled receptor 55 (GPR55) is expressed in multiple tissues, and
      has been implicated in cancer pathogenesis, but little is known about its role in
      the migratory behavior of cancer cells, particularly breast cancer cells. In this
      study we first showed that GPR55 expression levels in 38 metastatic lymph nodes
      of breast cancer patients were profoundly elevated, and were positively
      associated in human breast cancer cells with their migratory ability. Moreover,
      the plasma levels of GPR55 endogenous agonist L-a-lysophosphatidylinositol (LPI)
      were significantly increased in breast cancer patients compared with healthy
      individuals. In human breast cancer LM-MCF-7 and MDA-MB-231 cells, treatment with
      LPI (2.5 MUmol/L) significantly increased filopodia formation and resulted in
      cell migration, which could be blocked either by the GPR55 antagonist CID16020046
      or by siRNA-mediated GPR55 knockdown. Furthermore, dual-luciferase report gene
      assays showed that GPR55 upregulated HBXIP at the promoter; GPR55 expression
      levels were positively correlated with HBXIP expression levels in breast cancer
      tissues and 8 breast cancer cell lines. We also showed that the LPI/GPR55 axis
      promoted the migration of breast cancer cells via two mutually exclusive pathways
      - the HBXIP/p-ERK1/2/Capn4 and MLCK/MLC signaling pathways. In xenograft nude
      mouse model, loss of GPR55 mainly affected breast cancer cell metastasis and the
      formation of metastatic foci. Thus, GPR55 is involved in the migratory behavior
      of human breast cancer cells and could serve as a pharmacological target for
      preventing metastasis.

PMID- 29188805
TI  - Prevention: Rivaroxaban plus aspirin in CAD or PAD.

PMID- 29188803
TI  - Activation of human smooth muscle BK channels by hydrochlorothiazide requires
      cell integrity and the presence of BK beta1 subunit.
AB  - Thiazide-like diuretics are the most commonly used drugs to treat arterial
      hypertension, with their efficacy being linked to their chronic vasodilatory
      effect. Previous studies suggest that activation of the large conductance voltage
      and Ca2+-dependent K+ (BK) channel (Slo 1, MaxiK channel) is responsible for the
      thiazide-induced vasodilatory effect. But the direct electrophysiological
      evidence supporting this claim is lacking. BK channels can be associated with one
      small accessory beta-subunit (beta1-beta4) that confers specific biophysical and
      pharmacological characteristics to the current phenotype. The beta1-subunit is
      primarily expressed in smooth muscle cells (SMCs). In this study we investigated
      the effect of hydrochlorothiazide (HCTZ) on BK channel activity in native SMCs
      from human umbilical artery (HUASMCs) and HEK293T cells expressing the BK channel
      (with and without the beta1-subunit). Bath application of HCTZ (10 MUmol/L)
      significantly augmented the BK current in HUASMCs when recorded using the whole
      cell configurations, but it did not affect the unitary conductance and open
      probability of the BK channel in HUASMCs evaluated in the inside-out
      configuration, suggesting an indirect mechanism requiring cell integrity. In
      HEK293T cells expressing BK channels, HCTZ-augmented BK channel activity was only
      observed when the beta1-subunit was co-expressed, being concentration-dependent
      with an EC50 of 28.4 MUmol/L, whereas membrane potential did not influence the
      concentration relationship. Moreover, HCTZ did not affect the BK channel current
      in HEK293T cells evaluated in the inside-out configuration, but significantly
      increases the open probability in the cell-attached configuration. Our data
      demonstrate that a beta1-subunit-dependent mechanism that requires SMC integrity
      leads to HCTZ-induced BK channel activation.

PMID- 29188806
TI  - Obesity: Bariatric surgery helps BP control.

PMID- 29188807
TI  - Acute kidney injury: Preventing angiography-associated kidney injury.

PMID- 29188808
TI  - Diabetes: Further insights into SGLT2 inhibitors.

PMID- 29188809
TI  - Risk factors: Nuts reduce risk of cardiovascular disease.

PMID- 29188810
TI  - Cardioprotection: IL-11 is a potential therapeutic target in cardiovascular
      fibrosis.

PMID- 29188811
TI  - Cardiomyopathy: Takotsubo has long-lasting functional consequences.

PMID- 29188812
TI  - Antiplatelet therapy: Similar 1-year results for prasugrel and ticagrelor.

PMID- 29188813
TI  - Valvular disease: Mechanical versus biological valve prostheses.

PMID- 29188814
TI  - Vascular disease: PCSK9 inhibition in PAD.

PMID- 29188815
TI  - Inflammation: Association between hsCRP reduction and cardiac outcomes.

PMID- 29188816
TI  - Surgery: Restrictive versus liberal red-cell transfusion.

PMID- 29188817
TI  - Dietary sugar intake was associated with increased body fatness but decreased
      cardiovascular mortality in Chinese elderly: an 11-year prospective study of Mr
      and Ms OS of Hong Kong.
AB  - BACKGROUND/OBJECTIVES: Epidemiological studies suggest that sugar intake
      contributes to weight gain and increased risk of cardiovascular diseases (CVDs).
      However, this association is largely undefined in the elderly population. Our aim
      was to investigate the effect of sugar consumption on the subsequent changes in
      body fatness and CVD mortality in Chinese elderly. METHODS: A total of 2000 men
      and 2000 women aged ?65 years were recruited from 2001 to 2003. Dietary sugar
      intake was estimated based on a validated 329-item food frequency questionnaire
      and a local sugar database. Adiposity was measured using dual-energy X-ray
      absorptiometry at baseline and follow-up after 4 years. Mortality was ascertained
      by local death registry until March 2014. Multivariable linear and Cox regression
      were conducted to evaluate the association of sugar consumption on the changes in
      body fatness and CVD mortality. RESULTS: A total of 174 CVD deaths were
      documented within the total 37 999 person-years' follow-up. Significant positive
      association between sugar intake and increase in body fatness at follow-up after
      4 years was found in men but not in women. After adjustment for potential
      confounders, men who consumed 1% increase in added sugar had an increase in whole
      body fat by 0.043 kg (P=0.006), central fat by 0.029 kg (P=0.016) and peripheral
      fat by 0.026 kg (P=0.006). However, in both genders, after an average of 11.1
      year follow-up, compared with the lowest quintile, the highest intakes of added
      sugar were associated with significantly lowered CVD mortality by 74.9% (hazard
      ratio (HR) (95% confidence interval (CI)): 0.251(0.070, 0.899)) in a dose
      response manner (Ptrend=0.011). This association was attenuated to non
      significance by further adjustment of the change in body fatness (Ptrend=0.055).
      CONCLUSIONS: Thus higher sugar intake of the Chinese elderly was associated with
      increased adiposity in men but decreased CVD mortality. The current World Health
      Organization recommendation for the elderly should be reviewed.

PMID- 29188819
TI  - Colonic Bacteroides are positively associated with trabecular bone structure and
      programmed by maternal vitamin D in male but not female offspring in an
      obesogenic environment.
AB  - BACKGROUND/OBJECTIVES: The gut microbiota is determined early in life, possibly
      including pregnancy. Pioneering data suggest vitamin D, a nutrient important for
      bone health, affects this microbiota. We found that high maternal vitamin D
      lowered circulating lipopolysaccharide (LPS), improved intestinal barrier and
      bone health in male but not female offspring in an obesogenic environment. This
      study determined if high maternal dietary vitamin D programs Bacteroides and
      Prevotella and whether this associates with bone mineral content, density and
      structure of male and female adult offspring fed an obesogenic diet. METHODS:
      C57BL/6J females received an AIN93G diet with high or low vitamin D from before
      mating until weaning. Post-weaning, male and female offspring remained on their
      respective vitamin D level or were switched and fed a high fat and sucrose diet
      until killing (age 7 months). Bacteroides and Prevotella were quantified in dams'
      feces and offspring colonic contents. LPS concentrations, bone mineral density
      and content, strength and structure data were integrated from our previous
      studies in the same mice. Spearman correlations were completed between
      Bacteroides and LPS, and bone outcomes. RESULTS: There was a maternal vitamin D
      effect on colonic Bacteroides but not Prevotella (dam diet: <0.001 and 0.735) in
      adult male offspring, independent of dams fecal Bacteroides before birth
      (P=0.998). In males, but not females, Bacteroides correlated with LPS (r=-0.488,
      P=0.018), trabecular femur peak load (r=0.362, P=0.033), vertebral trabecular
      separation (r=-0.605, P=0.006), trabecular number (r=0.614, P=0.005) and bone
      volume fraction (r=0.549, P=0.015). CONCLUSIONS: Dietary vitamin D programs
      Bacteroides in male adult offspring only, which correlated negatively with
      systemic inflammation and positively with bone strength and structure. This may
      have implications on maternal diet and nutritional guidelines targeting sexes in
      a different manner.

PMID- 29188818
TI  - No evidence of white adipocyte browning after endurance exercise training in
      obese men.
AB  - BACKGROUND/OBJECTIVES: The phenomenon of adipocyte 'beiging' involves the
      conversion of non-classic brown adipocytes to brown-like adipose tissue with
      thermogenic, fat-burning properties, and this phenomenon has been shown in
      rodents to slow the progression of obesity-associated metabolic diseases. Rodent
      studies consistently report adipocyte beiging after endurance exercise training,
      indicating that increased thermogenic capacity in these adipocytes may underpin
      the improved health benefits of exercise training. The aim of this study was to
      determine whether prolonged endurance exercise training induces beige
      adipogenesis in subcutaneous adipose tissues of obese men. SUBJECTS/METHODS:
      Molecular markers of beiging were examined in adipocytes obtained from abdominal
      subcutaneous (AbSC) and gluteofemoral (GF) subcutaneous adipose tissues before
      and after 6 weeks of endurance exercise training in obese men (n=6, 37.3+/-2.3
      years, 30.1+/-2.3 kg m-2). RESULTS: The mRNAs encoding the brown or beige
      adipocyte-selective proteins were very lowly expressed in AbSC and GF adipose
      tissues and exercise training did not alter the mRNA expression of UCP1, CD137,
      CITED, TBX1, LHX8 and TCF21. Using immunohistochemistry, neither multilocular
      adipocytes, nor UCP1 or CD137-positive adipocytes were detected in any sample.
      MicroRNAs known to regulate brown and/or beige adipose development were highly
      expressed in white adipocytes but endurance exercise training did not impact
      their expression. CONCLUSIONS: The present study reaffirms emerging data in
      humans demonstrating no evidence of white adipose tissue beiging in response to
      exercise training, and supports a growing body of work demonstrating divergence
      of brown/beige adipose location, molecular characterization and physiological
      function between rodents and humans.

PMID- 29188821
TI  - Response to "How much does the Addiction-Like eating behaviour scale add to the
      debate regarding food versus eating addictions?"

PMID- 29188820
TI  - Identification of novel alleles associated with insulin resistance in childhood
      obesity using pooled-DNA genome-wide association study approach.
AB  - BACKGROUND: Recently, we witnessed great progress in the discovery of genetic
      variants associated with obesity and type 2 diabetes (T2D), especially in adults.
      Much less is known regarding genetic variants associated with insulin resistance
      (IR). We hypothesized that novel IR genes could be efficiently detected in a
      population of obese children and adolescents who may not exhibit comorbidities
      and other confounding factors. OBJECTIVES: This study aimed to determine whether
      a genome-wide association study (GWAS), using a DNA-pooling approach, could
      identify novel genes associated with IR. SUBJECTS: The pooled-DNA GWAS analysis
      included Slovenian obese children and adolescents with and without IR matched for
      body mass index, gender and age. A replication study was conducted in another
      independent cohort with or without IR. METHODS: For the pooled-DNA GWAS, we used
      HumanOmni5-Quad SNP array (Illumina). Allele frequency distributions were
      compared with modified t-tests and chi2-tests and ranked using PLINK. Top single
      nucleotide polymorphisms (SNPs) were validated using individual genotyping by
      high-resolution melting analysis and TaqMan assay. RESULTS: We identified five
      top-ranking SNPs from the pooled-DNA GWAS analysis within the ECE1, IL1R2,
      GNPDA1, HLA-J and PYGB loci. All except SNP rs9261108 (HLA-J locus) were
      confirmed in the validation phase using individual genotyping. The SNP rs2258617
      within PYGB remained statistically significant for both recessive and additive
      models in both cohorts and in a merged analysis of both cohorts and present the
      strongest novel candidate gene for IR. CONCLUSION: We report for the first time a
      pooled-DNA GWAS approach to identify five novel SNPs or genes for IR in a
      paediatric population. The four loci confirmed in the second validation phase
      study warrant further studies, especially the strongest SNP rs2258617 within
      PYGB, and provide targets for further basic research of IR mechanisms and for the
      development of potential new IR and T2D therapies.

PMID- 29188822
TI  - Reticulocalbin-2 enhances hepatocellular carcinoma proliferation via modulating
      the EGFR-ERK pathway.
AB  - This corrects the article DOI: 10.1038/onc.2017.230.

PMID- 29188823
TI  - Corrigendum to: Minimum requirements for the estimation of the measurement
      uncertainty: Recommendations of the joint Working group for uncertainty of
      measurement of the CSMBLM and CCMB.
AB  - [This corrects the article DOI: 10.11613/BM.2017.030502.].

PMID- 29188824
TI  - Corrigenda: A new species of Pristimantis from eastern Brazilian Amazonia (Anura,
      Craugastoridae). ZooKeys 687: 101-129 (2017).
      https://doi.org/10.3897/zookeys.687.13221.
AB  - [This corrects the article DOI: 10.3897/zookeys.687.13221.].

PMID- 29188825
TI  - Ultrafast dynamics of ionic liquids in colloidal dispersion.
AB  - Ionic liquid (IL)-surfactant complexes have significance both in applications and
      fundamental research, but their underlying dynamics are not well understood. We
      apply polarization-controlled two-dimensional infrared spectroscopy (2D-IR) to
      study the dynamics of [BMIM][SCN]/surfactant/solvent model systems. We examine
      the effect of the choice of surfactants and solvent, and the IL-to-surfactant
      ratio (W-value), with a detailed analysis of the orientation and structural
      dynamics of each system. Different surfactants create very different environments
      for the entrapped ILs, ranging from a semi-static micro-environment to a
      fluxional environment that evolves even faster than the bulk IL. The oil-phase
      also clearly affects the microscopic dynamics. The anisotropy decay for entrapped
      ILs completes within 10 ps, which is similar to free thiocyanate ion in water,
      while a significant reorientation-induced spectral diffusion (RISD) effect is
      observed. The entrapped ionic liquid are highly dynamic for all W-values, and no
      core-shell structure is observed. We hypothesize that, instead of an ionic liquid
      reverse micelle (IL-RM), the microscopic structure of this system is small
      colloidal dispersions or pairs of IL and surfactants. A detailed analysis of the
      polarization-controlled 2D-IR spectra of AOT system reveals a potential ion
      exchange mechanism.

PMID- 29188826
TI  - Tuning the dual emissions of a monoruthenium complex with a dangling coordination
      site by solvents, O2, and metal ions.
AB  - A polypyridyl monoruthenium complex with a dangling coordination site shows dual
      fluorescence/phosphorescence emissions at room temperature. The emission
      properties can be modulated by multiple stimuli including solvents, O2, and metal
      ions.

PMID- 29188827
TI  - Supramolecular organization of a H-bonded perylene bisimide organogelator
      determined by transmission electron microscopy, grazing incidence X-ray
      diffraction and polarized infra-red spectroscopy.
AB  - An organogelator based on a N,N'-substituted H-bonding perylenebisimide (PBI-C10)
      self-assembles to form either a green J-type (form I) or a red H-type (form II)
      aggregate structure. The molecular packing of both polymorphs was determined from
      a combination of Transmission Electron Microscopy (TEM) (low dose electron
      diffraction and high resolution), Grazing incidence X-ray diffraction and
      polarized infrared spectroscopy. To that aim, highly oriented films have been
      prepared by mechanical rubbing at controlled film temperature and DFT
      calculations were performed to identify representative vibrational IR bands and
      their associated polarizations. H-Bonding between amides generates either a
      rectangular columnar phase (form I) in the dried gel or a hexagonal packing of
      supramolecular 21/1 helices with a long period of 97 A (form II) in annealed thin
      films. In aligned films of form I, polarized FTIR spectroscopy helps determine
      the orientation of both intermolecular H-bonds and the PBI core with respect to
      the substrate. In form II, PBI-C10 molecules assemble into pairs to form off
      centered 21/1 helices whose helical axis is made of strongly H-bonded amides. TEM
      investigations show that three 21/1 helices are packed in a frustrated trigonal
      structure formed by H-bonding. The Form I -> Form II transformation implies a
      redistribution of a single population of strong intra-columnar H-bonds between
      amides in form I to a mixture of strong and weak H-bonds in the supramolecular
      helices, the strong H-bonds forming the spine of the helices.

PMID- 29188828
TI  - Using ZnO-Cr2O3-ZnO heterostructures to characterize polarization penetration
      depth through non-polar films.
AB  - The ability to affect the surface properties of non-polar Cr2O3 films through
      polar ZnO(0001) and (0001[combining macron]) supports was investigated by
      characterizing the polarity of ZnO films grown on top of the Cr2O3 surfaces. The
      growth and geometric and electronic structures of the ZnO films were
      characterized with X-ray photoelectron spectroscopy, ultra-violet photoelectron
      spectroscopy, reflection high-energy electron diffraction, low-energy electron
      diffraction, and X-ray diffraction. The ZnO growth mode was Stranski-Krastanov,
      which can be attributed to the ZnO layers initially adopting a non-polar
      structure with a lower surface tension before transitioning to the polar bulk
      structure with a higher surface energy. A similar result has been reported for
      ZnO growth on alpha-Al2O3(0001), which is isostructural with Cr2O3. The polarity
      of the added ZnO layer was determined by examining the surface morphology
      following wet chemical etching with atomic force microscopy and by characterizing
      the surface reactivity via temperature-programmed desorption of alcohols, which
      strongly depends on the ZnO polarization direction. Consistent with prior work on
      ZnO growth on bulk Cr2O3(0001), both measurements indicate that thick Cr2O3
      layers support ZnO(0001[combining macron]) growth regardless of the underlying
      ZnO substrate polarization; however, the polarization direction of ZnO films
      grown on Cr2O3 films less than three repeat units thick follows the direction of
      the underlying substrate polarization. These findings show that it is possible to
      manipulate the surface properties of non-polar materials with a polar substrate,
      but that the effect does not penetrate past just a couple of repeat units.

PMID- 29188829
TI  - Solvent effects on excitation energies obtained using the state-specific TD-DFT
      method with a polarizable continuum model based on constrained equilibrium
      thermodynamics.
AB  - Nonequilibrium solvation effects need to be treated properly in the study of
      electronic absorption processes of solutes since solvent polarization is not in
      equilibrium with the excited-state charge density of the solute. In this work, we
      developed a state specific (SS) method based on the novel nonequilibrium
      solvation model with constrained equilibrium manipulation to account for
      solvation effects in electronic absorption processes. Time-dependent density
      functional theory (TD-DFT) is adopted to calculate electronic excitation energies
      and a polarizable continuum model is employed in the treatment of bulk solvent
      effects on both the ground and excited electronic states. The equations based on
      this novel nonequilibrium solvation model in the framework of TDDFT to calculate
      vertical excitation energy are presented and implemented in the Q-Chem package.
      The implementation is validated by comparing reorganization energies for charge
      transfer excitations between two atoms obtained from Q-Chem and those obtained
      using a two-sphere model. Solvent effects on electronic transitions of coumarin
      153 (C153), acetone, pyridine, (2E)-3-(3,4-dimethoxyphenyl)-1-(2
      hydroxyphenyl)prop-2-en-1-one (DMHP), and uracil in different solvents are
      investigated using the newly developed code. Our results show that the obtained
      vertical excitation energies as well as spectral shifts generally agree better
      with the available experimental values than those obtained using the traditional
      nonequlibrium solvation model. This new model is thus appropriate to study
      nonequilibrium excitation processes in solution.

PMID- 29188830
TI  - Synthesis and applications of rhodium porphyrin complexes.
AB  - Organotransition metal complexes capable of forming metalloradicals have been an
      intriguing subject of study for the past fifty years. Of these, rhodium porphyrin
      complexes have proven particularly interesting due to their straightforward
      synthesis and unique reactivity; indeed, these complexes are responsible for some
      highly influential transformations of organic compounds, including rare C-H and C
      C bond activations. The complexity and selectivity of rhodium porphyrins has been
      attractive for catalytic transformations, with specific interest in their usage
      for selective carbon monoxide reduction for fuel cell applications. This review
      will highlight historical and modern syntheses of rhodium porphyrins, as well as
      their respective reactions with small molecules and applications therein. The
      discussion will be limited to rhodium porphyrins consisting of four pyrrolic
      rings bridged with four methine units.

PMID- 29188831
TI  - Spin-polarized transport properties in some transition metal dithiolene
      complexes.
AB  - Spin filtering materials are of great current interest in part due to their
      applications in molecular electronics. In this study, we carried out a
      theoretical investigation on the charge transport properties of transition metal
      (TM) dithiolene complexes with TM = Ni, Fe and Mn by using non-equilibrium
      Green's function/density functional theory (NEGF-DFT) methods. The
      characteristics of current-voltage and spin-resolved transmission spectra pointed
      out that Ni complexes are non-polarized, while Fe and Mn complexes exhibit high
      polarization and can be regarded as excellent candidates for spin-filtering
      materials with high spin-filtering efficiency. These differences were
      rationalized on the basis of electron delocalization over the molecular junction
      of the partial distribution of alpha- and beta-spin molecular projected self
      consistent Hamiltonian (MPSH) orbitals, and also the first eigenchannels of
      molecular junctions.

PMID- 29188832
TI  - The aromatic character of [10]annulenes and dicupra[10]annulenes from current
      density calculations.
AB  - We have investigated the aromatic properties of seven low-lying isomers of
      [10]annulene and of the recently synthesized dicupra[10]annulene compounds that
      were crystallised with two or four lithium counterions (Wei et al., J. Am. Chem.
      Soc., 2016, 138, 60-63). The molecular structures of the [10]annulene conformers
      and the dicupra[10]annulenes with bulky trimethylsilyl (TMS) and phenyl groups,
      as well as the corresponding unsubstituted dicupra[10]annulenes were optimised
      using density functional theory, employing a semi-empirical dispersion correction
      to consider van der Waals interactions. The structures of the hydrocarbon
      annulenes were subsequently optimised at the SCS-MP2/def2-QZVPD level. Single
      point coupled-cluster calculations with explicit treatment of the electron
      correlation CCSD(F12)(T) were performed to obtain the relative energies of the
      hydrocarbon annulenes. Four of the conformations lie close in energy relative to
      each other. Three substituted and three unsubstituted dicupra[10]annulene
      structures with either four, two or no Li+ counterions were investigated.
      Magnetically induced current densities calculated using the GIMIC program were
      used for the assessment of the aromatic properties of the studied molecules. The
      conformations of [10]annulene with lowest energies are non-aromatic. The
      calculations revealed that the electron donation of the lithium atoms to the
      dicupra[10]annulene core significantly affects the electronic and molecular
      structures of the dicupra[10]annulenes. The annulene ring is non-planar for all
      studied dicupra[10]annulenes except for the unsubstituted one with four Li+
      counterions, which was also found to be the only molecule that sustains a strong
      diatropic ring current around the dicupra[10]annulene ring. The other five
      dicupra[10]annulenes sustain very weak net ring currents and can be considered
      non-aromatic.

PMID- 29188833
TI  - A covalently conjugated MoS2/Fe3O4 magnetic nanocomposite as an efficient &
      reusable catalyst for H2 production.
AB  - Quick and easy recovery without the loss of the photocatalytic activity of the
      catalysing agent is an effective way to meet the challenges associated with the
      high cost of hazard-free hydrogen production. A '2D/0D' covalently conjugated
      nanocomposite of MoS2/Fe3O4 has shown efficient catalyzing ability for five
      cycles of dye-sensitized H2 evolution.

PMID- 29188834
TI  - Detection of a weak ring current in a nonaromatic porphyrin nanoring using
      magnetic circular dichroism.
AB  - We compare the absorption and magnetic circular dichroism (MCD) spectra of a
      series of porphyrin oligomers - dimer, tetramer, and hexamer - bound in a linear
      or cyclic fashion. The MCD signal is extremely weak for low energy transitions in
      the linear oligomers, but it is amplified when the cyclic porphyrin hexamer binds
      a template, restricting rotational freedom. The appearance of Faraday A terms in
      the MCD spectra demonstrates the presence of a magnetic moment, and thus,
      uncompensated electronic current. The value of the excited state magnetic moment
      estimated from the A term is very low compared with those of monomeric
      porphyrins, which confirms the nonaromatic character of the cyclic array and the
      lack of a global ring current in the ground state of the neutral nanoring. DFT
      calculations predict the absorption and MCD patterns reasonably well, but fail to
      reproduce the MCD sign inversion observed in substituted monomeric zinc
      porphyrins ("soft" chromophores). Interestingly, a correct sign pattern is
      predicted by INDO/S calculations. Analysis of the MCD spectra of the monomeric
      porphyrin unit allowed us to distinguish between two close-lying lowest energy
      transitions, which some previous assignments placed further apart. The present
      results prove the usefulness of MCD not only for deconvolution and assignment of
      electronic transitions, but also as a sensitive tool for detecting electronic
      ring currents.

PMID- 29188835
TI  - Dynamics of transient species via anion photodetachment.
AB  - The dynamics of chemical reactions are often governed by transient species,
      including the transition state for activated bimolecular reactions. Such
      transient species are difficult to study experimentally, but it has proven
      valuable to prepare and probe transition-state dynamics by the photodetachment of
      anions with an equilibrium geometry similar to the neutral transition state. In
      this review, recent experimental advances in photoelectron and photoelectron
      photofragment coincidence spectroscopy are discussed, as well as the latest
      progress in the calculation of multidimensional potential energy surfaces and
      quantum dynamics calculations that have enabled an extension of studies of
      transition-state dynamics to increasingly multidimensional polyatomic systems.
      Examples of important dynamical effects such as mode specificity, tunneling,
      resonance and product energy disposal in reaction dynamics are discussed.

PMID- 29188836
TI  - Dissociation of haemolytic and oligomer-preventing activities of gramicidin S
      derivatives targeting the amyloid-beta N-terminus.
AB  - The intrinsic haemolysis of an amyloid-beta (Abeta) N-terminal targeting
      gramicidin S derivative was successfully dissociated from its Abeta oligomer
      preventing activities via Ala-scanning-based regulation of molecular
      amphiphilicity. The representative analogue DGR-7 shows low toxicity but
      significant efficiency in preventing Abeta oligomers and reducing amyloid plaques
      in APP/PS1 transgenic AD mice.

PMID- 29188837
TI  - Synthesis, spectroscopic characterisation and transmetalation of lithium and
      potassium diaminophosphanide-boranes.
AB  - A secondary diaminophosphane-borane (Et2N)2PH(BH3) was prepared from a
      chlorophosphane precursor and LiBH4 and metalated by reaction with anion bases (n
      BuLi, KN(SiMe3)2) to yield the corresponding metal diaminophosphanide-boranes
      [(Et2N)2P(BH3)]M (M = Li, K). Multinuclear NMR studies permitted the first
      spectroscopic characterisation of the metalation products and revealed the
      presence of monomeric (for M = Li) contact ion pairs in solution. NMR
      spectroscopic evidence that the ions in each pair interact via LiP- rather than
      LiH3B-interactions as had been inferred for a Ph-substituted analogue was
      confirmed by DFT studies, which revealed also that the borane coordination plays
      a decisive role in boosting the PH-acidity of the original secondary
      diaminophosphane precursor. Transmetalation of the potassium and lithium
      diaminophosphanide-boranes with Cu(i) and Zn(ii) chlorides afforded the first
      functional transition metal complexes of a P-heteroatom-functionalised
      phosphanide-borane ligand. Both products were fully characterised. Thermolysis of
      the Cu-complex induced a reaction which involved transfer of an NHC ligand from
      the metal to the phosphorus atom and yielded a phosphaalkene NHC[double bond,
      length as m-dash]PH (NHC = N-heterocyclic carbene) as the major phosphorus
      containing product.

PMID- 29188838
TI  - Enantioselective intermolecular all-carbon [4+2] annulation via N-heterocyclic
      carbene organocatalysis.
AB  - The highly stereoselective intermolecular all-carbon [4+2] annulation between in
      situ generated acyclic dienolates and alpha,beta-unsaturated acyl azoliums is
      disclosed. The identification of 2-acyloxy-3-butenones as suitable diene
      precursors is the key to the success of this transformation. The corresponding
      highly functionalized cyclohexene products, which are inaccessible from Diels
      Alder reactions, were delivered with high levels of diastereo- and
      enantioselectivities. A series of further transformations based on the product
      showed the potential of this reaction.

PMID- 29188839
TI  - An antiparallel double-stranded BODIPY-porphyrin dyad assembled via a self
      complementary B-FZn interaction.
AB  - An antiparallel double-strand of a BODIPY-zinc-porphyrin dyad was assembled via
      geometrical complementarity of an unusual B-FZn coordination bonding interaction.

PMID- 29188840
TI  - Understanding the interplay between the solvent and nuclear rearrangements in the
      negative solvatochromism of a push-pull flexible quinolinium cation.
AB  - A detailed computational characterization of the one-photon absorption spectrum
      of a 2-((E)-2-[2,2']-bithiophenyl-5-yl-vinyl)-1-methyl-quinolinium cation in
      acetonitrile solution is presented. The main physico-chemical effects (solvation,
      vibronic progression) affecting the band position and shape are progressively
      introduced in the computational model, highlighting their relative role in the
      spectral profile. The reported results underline how an accurate reproduction of
      the experimental spectrum can only be obtained by going beyond oversimplified
      methods. Moreover, the deep interplay between the solvent effects and nuclear
      rearrangements permits the negative solvatochromism exhibited by hypsochromic
      molecules to be explained. This illustrates the potential of the computational
      investigation, which can shed light on the information hidden in experimental
      spectra.

PMID- 29188841
TI  - Temperature effect on the emission spectra of narrow band Mn4+ phosphors for
      application in LEDs.
AB  - Temperature dependence of the luminescence shape and decay time of narrow band
      Mn4+ fluoride phosphors: Rb2GeF6:Mn4+ and KNaSiF6:Mn4+ was investigated. The
      temperature changes in the relative intensity between the zero-phonon line and
      both phonon sidebands were observed in both samples. The sideband spectra consist
      of three lines related to interaction with three different phonon modes labeled
      nu3, nu4 and nu6. We present a comprehensive quantum theory which allows
      calculation of the luminescence intensity and the luminescence lifetime by
      simultaneously taking into account odd parity crystal fields, odd parity phonon
      modes and spin-orbit coupling. Since we include all modes, for which the
      respective interaction strengths and energies of the phonons are known, our
      approach does not involve any free parameters. We also discuss our results in
      relation to the temperature dependence of the lifetime of the 2Eg -> 4A2g
      transition, taking into account the quantum efficiency of the system and the
      migration of the excitation energy. The presented model is applicable to all
      materials doped with Mn4+ ions and also to any narrow line emitting phosphor,
      where a zero-phonon line and phonon structure is simultaneously observed in the
      emission spectrum.

PMID- 29188842
TI  - Multiple polarization states in symmetric ferroelectric heterostructures for
      multi-bit non-volatile memories.
AB  - Here we report a ferroelectric capacitor structure obtained by alternating
      ferroelectric and insulator thin-film layers which allows an increase of up to 2n
      polarization states, with n the number of ferroelectric layers. Four and up to
      eight distinct, stable and independently addressed polarization states are
      experimentally demonstrated in this work. The experimental findings are supported
      by a theoretical model based on the Landau-Ginzburg-Devonshire theory. The key
      parameter is the change in the strain conditions of ferroelectric layers induced
      by the insulating separator. Notably, the 2n increase in the storage capacity can
      be achieved without major changes in the present technology used for FeRAM
      devices. The test structures demonstrate very good memory characteristics such as
      retention and fatigue, opening the way towards the design of high density
      ferroelectric memories.

PMID- 29188843
TI  - Effect of suberoylanilide hydroxamic acid (SAHA) on breast cancer cells within a
      tumor-stroma microfluidic model.
AB  - Metastatic cancer is regarded as one of the largest contributors to disease
      related deaths worldwide. Poor patient prognosis and treatment outcome is tied to
      the lack of efficacious anti-cancer therapies, which is due in part to the lack
      of physiologically relevant in vitro screening systems that can mimic the native
      tumor microenvironment. Conventional drug-screening platforms, which are often
      used in the pharmaceutical industry, are either two-dimensional (2D) assays or
      three-dimensional (3D) hydrogel-based matrices that lack precise control over
      cell distribution, matrix architecture, and organization. Despite the
      significance of in vivo models, they have limitations as it is difficult to
      control and analyze the influence of specific variables within their tumor
      microenvironment. Thus, there is still a crucial need to develop tumor models
      that enable precise control of microenvironmental cues (e.g. matrix composition,
      soluble factors, cellular organization) to assess the efficacy of anti-cancer
      drugs. Herein, we report the development and validation of a 3D microfluidic
      invasion platform for anti-cancer drug studies. Our platform allowed for
      compartmentalization of tumor and stromal fibroblasts in a defined architecture,
      thereby enabling pharmacokinetic drug transport to a cell-dense tumor region. We
      analyzed the effect of suberoylanilide hydroxamic acid (SAHA), a histone
      deacetylase (HDAC) inhibitor, on the behavior of SUM159 breast cancer cells. Many
      HDAC inhibitors, including SAHA, have been a subject of controversy with highly
      conflicting results for the treatment of solid tumors in vitro as well as in
      clinical trials. We found that SAHA significantly inhibited cellular
      migration/proliferation, and decreased microtubule polarization.

PMID- 29188844
TI  - Poly(ferrocenylsilane) electrolytes as a gold nanoparticle foundry: "two-in-one"
      redox synthesis and electrosteric stabilization, and sensing applications.
AB  - Gold nanoparticles (AuNPs) coated with responsive polymers gained considerable
      interest due to their controllable size, good stability, and fast environmental
      response suitable for biological applications and sensing. Here we report on a
      simple and efficient method for the synthesis of stable and redox responsive
      AuNPs using organometallic polyelectrolytes in aqueous solutions of HAuCl4. In
      the redox reaction, positively or negatively charged poly(ferrocenylsilanes)
      (PFS+/PFS-) served as reducing agents, and also as stabilizing polymers. Due to
      their unique tunable electrostatic and electrosteric protection, AuNPs coated
      with PFS-, (PFS+)@AuNPs, possess high redox sensitivity, with reversible,
      repetitive, sustainable color switching between the assembled (purple color) and
      disassembled (red color) states as evidenced by UV-Vis absorption and TEM
      measurements. Feasibility studies reported here indicate that the particles
      described can be applied as a colorimetric probe for the detection of redox
      molecules, e.g. vitamin C, in a controlled and facile manner.

PMID- 29188845
TI  - Molecular targets and mechanisms of bioactive peptides against metabolic
      syndromes.
AB  - Bioactive peptides are present in all living organisms and have critical roles
      ranging from protection against infection as the key element of innate immunity,
      regulating blood pressure and glucose levels, to reducing signs of ageing by
      killing senescent cells. Bioactive peptides are also encrypted within food
      protein sequences that can be released during proteolysis or food processing.
      These specific food protein fragments are reported to have potential for
      improving human health and preventing metabolic diseases through their impact on
      inflammation, blood pressure, obesity, and type-2 diabetes. This review mainly
      focuses on the molecular targets and the underlying mechanisms of bioactive
      peptides against various metabolic syndromes including inflammation, high blood
      pressure, obesity, and type-2 diabetes, to provide new insights and perspectives
      on the potential of bioactive peptides for management of metabolic syndromes.

PMID- 29188846
TI  - Structure and dynamics of ionic liquids: general discussion.

PMID- 29188847
TI  - An extremely low Pt loading cathode for a highly efficient proton exchange
      membrane water electrolyzer.
AB  - Direct self-terminated Pt electrodeposition on carbon paper enables precise
      control of loading Pt mass, from the sub-microgram to the sub-milligram scale.
      This can provide insight into the low limits of Pt use for reasonable performance
      of a proton exchange membrane water electrolyzer.

PMID- 29188848
TI  - Bacterial self-defense antibiotics release from organic-inorganic hybrid
      multilayer films for long-term anti-adhesion and biofilm inhibition properties.
AB  - Implant-associated bacterial infections pose serious medical and financial issues
      due to the colonization and proliferation of pathogens on the surface of the
      implant. The as-prepared traditional antibacterial surfaces can neither resist
      bacterial adhesion nor inhibit the development of biofilm over the long term.
      Herein, novel (montmorillonite/poly-l-lysine-gentamicin sulfate)8 ((MMT/PLL-GS)8)
      organic-inorganic hybrid multilayer films were developed to combine enzymatic
      degradation PLL for on-demand self-defense antibiotics release. Small molecule GS
      was loaded into the multilayer films during self-assembly and the multilayer
      films showed pH-dependent and linear growth behavior. The chymotrypsin- (CMS) and
      bacterial infections-responsive film degradation led to the peeling of the films
      and GS release. Enzyme-responsive GS release exhibited CMS concentration
      dependence as measured by the size of the inhibition zone and SEM images.
      Notably, the obtained antibacterial films showed highly efficient bactericidal
      activity which killed more than 99.9% of S. aureus in 12 h. Even after 3 d of
      incubation in S. aureus, E. coli or S. epidermidis solutions, the multilayer
      films exhibited inhibition zones of more than 1.5 mm in size. Both in vitro and
      in vivo antibacterial tests indicated good cell compatibility, and anti
      inflammatory, and long-term bacterial anti-adhesion and biofilm inhibition
      properties.

PMID- 29188849
TI  - Surface properties of MoS2 probed by inverse gas chromatography and their impact
      on electrocatalytic properties.
AB  - Layered transition metal dichalcogenides (TMDs) are at the forefront of materials
      research. One of the most important applications of these materials is their
      electrocatalytic activity towards hydrogen evolution, and these materials are
      suggested to replace scarce platinum. Whilst there are significant efforts
      towards this goal, there are various reports of electrocatalysis of MoS2 (which
      is the most commonly tested TMD) with large variations of the reported
      electrocatalytic effect of the material, with overpotential varying by several
      hundreds of millivolts. Here, we analyzed surface properties of various bulk as
      well as single layer MoS2 samples using inverse gas chromatography. All samples
      displayed significant variations in surface energies and their heterogeneities.
      The surface energy ranged from 50 to 120 mJ m-2 depending on the sample and
      surface coverage. We correlated the surface properties and previously reported
      structural features of MoS2 with their electrochemical activities. We concluded
      that the observed differences in electrochemistry are caused by the surface
      properties. This is an important finding with an enormous impact on the whole
      field of electrocatalysis of layered materials.

PMID- 29188850
TI  - Fabrication of carbon quantum dots with nano-defined position and pattern in one
      step via sugar-electron-beam writing.
AB  - Quantum dots (QDs) are promising materials in nanophotonics, biological imaging,
      and even quantum computing. Precise positioning and patterning of QDs is a
      prerequisite for realizing their actual applications. Contrary to the traditional
      two discrete steps of fabricating and positioning QDs, herein, a novel sugar
      electron-beam writing (SEW) method is reported for producing QDs via electron
      beam lithography (EBL) that uses a carefully chosen synthetic resist, poly(2
      (methacrylamido)glucopyranose) (PMAG). Carbon QDs (CQDs) could be fabricated in
      situ through electron beam exposure, and the nanoscale position and luminescence
      intensity of the produced CQDs could be precisely controlled without the
      assistance of any other fluorescent matter. We have demonstrated that upon
      combining an electron beam with a glycopolymer, in situ production of CQDs occurs
      at the electron beam spot center with nanoscale precision at any place and with
      any patterns, an advancement that we believe will stimulate innovations in future
      applications.

PMID- 29188851
TI  - Physiological responses and toxin production of Microcystis aeruginosa in short
      term exposure to solar UV radiation.
AB  - The aim of this study was to evaluate the effects of short-term (hours) exposure
      to solar UV radiation (UVR, 280-400 nm) on the physiology of Microcystis
      aeruginosa. Three solar radiation treatments were implemented: (i) PAR (PAR, 400
      700 nm), (ii) TUVA (PAR + UVAR, 315-700 nm) and (iii) TUVR (PAR + UVAR + UVBR,
      280-700 nm). Differential responses of antioxidant enzymes and the reactive
      oxygen species (ROS) production to UVR were observed. Antioxidant enzymes were
      more active at high UVR doses. However, different responses were observed
      depending on the exposure to UVAR or UVBR and the dose level. No effects were
      observed on the biomass, ROS production or increased activity of superoxide
      dismutase (SOD) and catalase (CAT) compared to the control when UVR + PAR doses
      were lower than 9875 kJ m-2. For intermediate doses, UVR + PAR doses between 9875
      and 10 275 kJ m-2, oxidative stress increased while resistance was imparted
      through SOD and CAT in the cells exposed to UVAR. Despite the increased
      antioxidant activity, biomass decrease and photosynthesis inhibition were
      observed, but no effects were observed with added exposure to UVBR. At the
      highest doses (UVR + PAR higher than 10 275 kJ m-2), the solar UVR caused
      decreased photosynthesis and biomass with only activation of CAT by UVBR and SOD
      and CAT by UVAR. In addition, for such doses, a significant decrease of
      microcystins (MCs, measured as MC-LR equivalents) was observed as a consequence
      of UVAR. This study facilitates our understanding of the SOD and CAT protection
      according to UVAR and UVBR doses and cellular damage and reinforces the
      importance of UVR as an environmental stressor. In addition, our results support
      the hypothesized antioxidant function of MCs.

PMID- 29188852
TI  - Temperature-dependent IR-transition moment orientational analysis applied to thin
      supported films of poly-epsilon-caprolactone.
AB  - A novel experimental setup is described which enables one to carry out infrared
      transition moment orientational analysis (IR-TMOA) depending on temperature. By
      this, three dimensional molecular order parameter tensors of IR-active transition
      dipole moments with respect to the sample coordinate system can be determined in
      their thermal evolution (35  degrees C < T < 59  degrees C). As an example
      crystallinity and macroscopic order of poly-epsilon-caprolcatone are monitored.
      Both remain largely unaltered up to T ~ 50  degrees C, above which they decrease.
      These reductions are explained as the melting of flat-on crystalline lamellae
      that make up about 34% of the crystalline material. The remaining crystallites
      are arranged into bulk-like, confined spherulitic structures and do not melt by
      more than (3 +/- 3)%. Therefore, flat-on oriented lamellae are supposed to be
      kinetically favored by confinement during melt crystallization but are
      thermodynamically less stable than two-dimensionally confined bulk-like
      spherulites.

PMID- 29188853
TI  - Computerized Cognitive Testing for Use in Clinical Trials: A Comparison of the
      NIH Toolbox and Cogstate C3 Batteries.
AB  - BACKGROUND: As prevention trials for Alzheimer's disease move into asymptomatic
      populations, identifying older individuals who manifest the earliest cognitive
      signs of Alzheimer's disease is critical. Computerized cognitive testing has the
      potential to replace current gold standard paper and pencil measures and may be a
      more efficient means of assessing cognition. However, more empirical evidence
      about the comparability of novel computerized batteries to paper and pencil
      measures is required. OBJECTIVES: To determine whether two computerized IPad
      batteries, the NIH Toolbox Cognition Battery and Cogstate-C3, similarly predict
      subtle cognitive impairment identified using the Preclinical Alzheimer Cognitive
      Composite (PACC). DESIGN, SETTING, PARTICIPANTS: A pilot sample of 50 clinically
      normal older adults (Mage=68.5 years+/-7.6, 45% non-Caucasian) completed the PACC
      assessment, and the NIH Toolbox and Cogstate-C3 at research centers of
      Massachusetts General and Brigham and Women's Hospitals. Participants made 3-4 in
      clinic visits, receiving the PACC first, then the NIH Toolbox, and finally the
      Cogstate-C3.>= 0.5SD), versus subtle cognitive impairment (<0.5SD). Composites
      for each computerized battery were created using principle components analysis,
      and compared with the PACC using non-parametric Spearman correlations. Logistic
      regression analyses were used to determine which composite was best able to
      classify subtle cognitive impairment from typical performance. RESULTS: The NIH
      Toolbox formed one composite and exhibited the strongest within-battery
      alignment, while the Cogstate-C3 formed two distinct composites (Learning-Memory
      and Processing Speed-Attention). The NIH Toolbox and C3 Learning-Memory
      composites exhibited positive correlations with the PACC (rho=0.49, p<0.001;
      rho=0.58, p<0.001, respectively), but not the C3 Processing Speed-Attention
      composite, rho=-0.18, p=0.22. The C3 Learning-Memory was the only composite that
      classified subtle cognitive impairment, and demonstrated the greatest sensitivity
      (62%) and specificity (81%) for that subtle cognitive impairment. CONCLUSIONS:
      Preliminary findings suggest that the NIH Toolbox has the advantage of showing
      the strongest overall clustering and alignment with standardized paper-and-pencil
      tasks. By contrast, Learning-Memory tasks within the Cogstate-C3 battery have the
      greatest potential to identify cross-sectional, subtle cognitive impairment as
      defined by the PACC.

PMID- 29188854
TI  - Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived
      Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double
      Blind, Randomized Clinical Trial.
AB  - BACKGROUND: The prevalence of senile dementia is increasing worldwide, especially
      in the developed countries. Nevertheless, drug therapy isn't often enough to
      treat this condition. Researchers are evaluating the possible impact of a
      preventive approach, based on an improvement of lifestyle and the intake of
      micronutrients. Moreover, there is an increasing interest for combined
      nutraceuticals that can act as memory and learning enhancers, with a significant
      and beneficial potential on the cognitive disorders. OBJECTIVE: To evaluate the
      effects of a rational assemblage of nutraceuticals on cognitive functions in a
      sample of 30 elderly subjects. DESIGN: Double bind, cross-over designed trial
      versus placebo Setting: outpatient clinical practice. PARTICIPANTS: 30 elderly
      subjects with basal Mini-Mental State Examination score between 20 and 27 and
      self-perceived cognitive decline. INTERVENTION: Treatment with a combination of
      nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper,
      folate and vitamins of B and D group. After2 months of treatment or placebo.
      MEASUREMENTS: Patients were evaluated with Mini-Mental State Examination (MMSE),
      Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale
      (SRDS). RESULTS: MMSE and PSQ Index significantly improved in the active
      treatment arm, both versus baseline and versus the parallel arm. Both groups
      experienced a significant improving in the SRDS scores. CONCLUSIONS: We obtained
      a good and significant improvement of the cognitive functions tested with the
      MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of
      nutraceuticals. Further confirmation will be needed to verify these observations
      on the middle and long term in a larger number of subjects.

PMID- 29188855
TI  - Ginkgo Biloba Extract Consumption and Long-Term Occurrence of Death and Dementia.
AB  - OBJECTIVES: To study the benefit of Ginkgo Biloba Extract (GBe) consumption on
      the long term risk of dementia and death in elderly people. DESIGN: The Paquid
      study is a population-based cohort with regular follow-up screenings up to twenty
      two years and systematic detection of incident cases of dementia. Statistical
      analysis was conducted with an illness-death model dealing with interval
      censoring of dementia and competing risk of death. SETTING: The sample was
      randomly selected from electoral rolls in two administrative areas of
      southwestern France in 1988-1989. PARTICIPANTS: 3,777 subjects aged 65 years or
      older at baseline who were living at home. MEASUREMENT: Participants were visited
      at home by a trained psychologist at baseline in 1988/1989, and then again
      approximately every two years. Drug consumption for the treatment of cognitive or
      neurosensory impairment was collected at baseline. Participants were classified
      as GBe consumers, other drug (OD) consumers and untreated controls (UC) for this
      motive. RESULTS: After adjustment for sociodemographic factors and cognitive
      measures at baseline the risk for dementia was not significantly different in GBe
      consumers and UC (Hazard Ratio (HR)=1.21, 95% Confidence Interval (95% CI)=0.95
      1.55, p=0.42) and it was of the same magnitude but significantly increased in the
      OD group versus UC (HR=1.25, 95% CI=1.06-1.46, p=0.004). With the same
      adjustment, the risk of dying in non-demented subjects was reduced in GBe
      consumers versus UC (HR=0.67, 95% CI=0.49-0.93, p=0.02) while it was the same as
      the reference group in OD consumers. The mean lifetimes without dementia was of
      11.2 years in the UC group (95% CI=10.9-11.5), 11.1 years in the GBe group (10.2
      11.9) and 9.1 years for the OD group (8.7-9.6). CONCLUSION: GBe consumers have a
      lower risk of dying before dementia and a longer lifetime without dementia than
      participants taking other drugs for the same indication.

PMID- 29188856
TI  - Stimulus-Locked Lateralized Readiness Potential and Performance: Useful Markers
      for Differentiating between Amnestic Subtypes of Mild Cognitive Impairment.
AB  - BACKGROUND: The findings of previous studies, in which event-related potentials
      (ERPs) related to stimulus evaluation were measured, do not fully explain the
      behavioral decline observed in amnestic mild cognitive impairment (aMCI;
      prodromal stage of Alzheimer's Disease). OBJECTIVES: Motor ERPs were evaluated in
      this study with the aim of discovering complementary explanations and identifying
      aMCI biomarkers. DESIGN: Cross-sectional study. SETTING: Santiago de Compostela,
      Galicia, Spain. PARTICIPANTS: Nineteen healthy control (52-81 years old), 21
      single-domain aMCI (sdaMCI; 51-87 years old) and 12 multi-domain aMCI (mdaMCI, 62
      85 years old) adults. MEASUREMENTS: Reaction times (RTs), percentage of hits, and
      stimulus-locked and response-locked lateralized readiness potentials (sLRP and
      rLRP, indexes of response selection and preparation) were evaluated. RESULTS:
      mdaMCI participants showed longer RTs than control adults and less hits than
      control and sdaMCI participants. In addition, the mdaMCI group showed lower sLRP
      amplitudes than the control participants, and the sdaMCI group showed longer sLRP
      peak latencies. CONCLUSIONS: Control and sdaMCI groups did not differ in relation
      to RTs or hits, although sLRP peak latencies (sensitivity and specificity >.73)
      were longer in the sdaMCI group, which may be a sign of compensatory mechanisms
      or early indication of a decline in motor control. RTs were longer and sLRP
      amplitudes were smaller in the mdaMCI than in the Control group, and mdaMCI
      scored fewer hits than control and sdaMCI participants, indicating behavioral and
      neurocognitive deficits. The combination of hits and RTs discriminated mdaMCI
      from control adults (sensitivity and specificity >.82); and the combination of
      sLRP peak latency and hits discriminated mdaMCI from sdaMCI adults
      (sensitivity=1.00, specificity=.88).

PMID- 29188857
TI  - Assessing the Relationship between Vitamin D Status and Impairments in Cognitive
      and Physical Performance in Older Adults Using a Dual Task Physical Performance
      Test.
AB  - BACKGROUND: Vitamin D deficiency has been associated with an increased risk of
      falls in older adults. Several studies have demonstrated an association between
      vitamin D deficiency and gait and cognitive impairments, which are two risk
      factors for falls in the elderly. There is lack of research about the role of
      vitamin D in cognitive function in the context of mobility. OBJECTIVE: The
      purpose of this study was to evaluate the association between vitamin D status
      with the age-related changes in mobility through higher order cognitive function
      using a dual task physical performance test. DESIGN: Cross-sectional. SETTING:
      Community-dwelling older adult population located in Miami, Fl. PARTICIPANTS:
      Healthy participants over the age of 55 (n=97) who participated in the parent
      interventional study. MEASUREMENTS: Participants completed assessments that
      included serum levels of vitamin D, surveys, and dual task physical performance
      tests. Spearman's correlations, independent t-tests, repeated measures ANOVAs and
      multiple logistic regressions were used to examine the relationship between
      vitamin D insufficiency (25-hydroxyvitamin D <30 ng/ml) and sufficiency (>=30
      ng/ml) and dual task physical performance variables. The significance level was
      set at alpha=0.05. RESULTS: There were no significant associations between
      vitamin D insufficiency and gait velocity during either task. Using Spearman
      correlations, slower single (P=0.011) and dual task counting rates (P=0.006) were
      significantly associated with vitamin D insufficiency. Independent t-tests showed
      dual and single task counting rates were significantly lower in the vitamin D
      insufficient group compared to the sufficient group (P=0.018 and P=0.028,
      respectively). The results for the ANOVAs indicated that velocities and counting
      rates were not significantly different by vitamin D status (Wilk's Lambda =0.999;
      F (1, 95) =.11, P=.740) (Wilk's Lambda =.999, F(1,95)=.13, P=.718). Vitamin D
      status was not significantly associated with dual task physical performance
      (defined as the difference in dual and single task) in gait velocity (OR=1.00,
      95% CI: 0.98; 1.02, P=0.772) and counting rate (OR=1.684, 95% CI: 0.15; 19.57,
      P=0.677), when controlling for confounders. CONCLUSIONS: Since counting backward
      is a mental tracking task, which is a component of executive function, our
      results suggest a relationship between vitamin D insufficiency and executive
      dysfunction. Executive dysfunction has been previously associated with fall risks
      in the elderly, and it could be a possible mediator between vitamin D and falls.
      Our data suggest that cognition may play a significant role in vitamin D's
      influence on falls, while motor function may play a lesser role.

PMID- 29188858
TI  - Modest Overweight and Healthy Dietary Habits Reduce Risk of Dementia: A
      Nationwide Survey in Taiwan.
AB  - BACKGROUND: Evidence of the associations of dietary habits and body mass index
      with dementia is inconsistent and limited in East Asian countries. OBJECTIVE: We
      aim to explore the associations of dietary habits and body mass index with the
      odds of dementia. DESIGN: Cross-sectional observational study. SETTING: A
      nationwide, population-based, door-to-door, in-person survey. PARTICIPANTS:
      Selected by computerized random sampling from all 19 counties in Taiwan.
      MEASUREMENT: Diagnosis of dementia using the criteria recommended by the National
      Institute on Aging-Alzheimer's Association. Lifestyle factors, dietary habits and
      demographic data were compared between normal subjects and participants with
      dementia. RESULTS: A total of 10432 residents were assessed, among whom 2049 were
      classified as having a mild cognitive impairment (MCI), 929 were diagnosed with
      dementia, and 7035 were without dementia or MCI. After adjustment for age,
      gender, education, body mass index (BMI), dietary habits, habitual exercises and
      co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we
      found inverse associations of dementia with the consumption of fish (OR 0.62, 95%
      CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI
      0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR
      0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit
      consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older
      overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted
      OR of 0.77 (95% CI 0.61-0.96). CONCLUSIONS: Our study provides preliminary
      evidence that suggests that the consumption of fish, vegetables, tea, and coffee
      has potential benefits against dementia in East Asian population. Being modestly
      overweight (nadir risk at BMI = 25) in late life was associated with decreased
      odds of dementia. The benefit of fruits may be offset by their high sugar
      content.

PMID- 29188860
TI  - A Keto-Mediet Approach with Coconut Substitution and Exercise May Delay the Onset
      of Alzheimer's Disease among Middle-Aged.
AB  - BACKGROUND: Coconut oil has been widely used to improve health because there is
      much information available by word of mouth, in books, and on the internet.
      However, researchers still continue to search for the best diets to improve the
      quality of life, especially for people with cognitive decline. OBJECTIVES: The
      aim of this review is to develop a novel dietary approach, the Keto-Mediet, which
      may help prevent the onset of Alzheimer's disease. METHODS: Evidence gained
      through literature review from 1982 to 2015 on gene-by-diet interaction and lipid
      and glucose metabolism in the brains of Alzheimer's patients is converted into
      the new Keto-Mediet approach. DESIGN: The Keto-Mediet approach combines the
      benefits of a Ketogenic diet and a Mediterranean diet into a pyramidal model that
      is rich in various types of vitamins and substitutes coconuts for saturated
      animal fats. Limited glucose intake is intended to delay brain degeneration. A
      revised adult food pyramid was created to illustrate the principles of the Keto
      Mediet approach. CONCLUSION: The Keto-Mediet approach represents and interprets
      food groups according to the revised adult food pyramid. This approach also
      encourages adherence to this healthy diet and lifestyle changes including
      exercise for people whose age ranges from 40 to 75 years. Those who comply with
      this approach will significantly enhance their knowledge and adopt a healthier
      lifestyle, as compared to those whose modern eating patterns are typically less
      healthy. Therefore, the Keto-Mediet approach can be applied in hopes of
      preventing and decreasing Alzheimer's disease in different ethnicities and
      cultural groups.

PMID- 29188859
TI  - Cognitive Performance Does not Limit Physical Activity Participation in the
      Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P).
AB  - OBJECTIVES: We examined whether multiple domains of baseline cognitive
      performance were associated with prospective physical activity (PA) adherence in
      the Lifestyle Interventions and Independence for Elders Pilot study (LIFE-P).
      DESIGN, SETTING, PARTICIPANTS: The LIFE-P study was a single-blind, multicenter,
      randomized controlled trial of a PA intervention compared to a successful aging
      educational intervention in sedentary, mobility-limited older adults.
      INTERVENTION: A 12-month structured, moderate-intensity, multi-modal PA program
      that included walking, resistance training, and flexibility exercises. For the
      first 2 months (adoption), 3 center-based exercise sessions (40-60 min) / week
      were conducted. During the next 4 months (transition), center-based sessions were
      conducted 2 times / week. The subsequent maintenance phase consisted of optional
      once-to-twice-per-week center-based sessions and home-based PA. MEASUREMENTS:
      Tests of executive and global cognitive functioning, working memory and
      psychomotor speed were administered at baseline. Median test scores were used to
      dichotomize participants into low or high cognitive performance groups. RESULTS:
      52 mobility-limited older adults (age: 76.9 +/-5 yrs) were randomized to the PA
      arm of LIFE-P. Compared to participants with high cognitive performance,
      participants with low performance had similar PA adherence rates (all P >= 0.34).
      Furthermore, weak and non-significant univariate relationships were elicited
      between all measures of cognition and overall PA adherence levels (r values
      ranged: -0.20 to 0.12, P >= 0.12). CONCLUSION: These data suggest that cognitive
      performance does not limit long-term PA adherence in mobility-limited older
      adults. Additional studies in larger cohorts are warranted to verify these
      findings.

PMID- 29188861
TI  - Antioxidants in the Diet and Cognitive Function: Which Role for the Mediterranean
      Life-style?
AB  - This review aims to focus on main antioxidants- abundantly contained in the diet-
      as well as of the whole Mediterranean diet and life-style and their relationship
      with cognitive function, especially critical in two phases of life, in children
      until adolescence and oldness. The role of emerging biochemical and molecular
      biomarkers as opportunity to estimate more accurately nutritional assumption and
      requirement, in terms of cognitive preservation and disease risk, will be also
      discussed. The cluster of factors within the Mediterranean pattern -which include
      not only nutritional, but also physical, social, and stimulating aspects- is
      still largely understudied as a whole, but it is proposed as attractive research
      area and tool for public health planning of prevention and intervention.

PMID- 29188862
TI  - Editorial: Collaborative Efforts to Prevent Alzheimer's Disease.

PMID- 29188863
TI  - Cross-Sectional Associations of Total Plasma Homocysteine with Cortical beta
      Amyloid Independently and as a Function of Omega 3 Polyunsaturated Fatty Acid
      Status in Older Adults at Risk of Dementia.
AB  - OBJECTIVES: Elevated total plasma homocysteine is a risk factor for Alzheimer's
      disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids
      (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD
      related pathologies. Hence we investigated the relationship between total plasma
      homocysteine and cortical beta-amyloid (Abeta) in older adults at risk of
      dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this
      relationship was also explored. DESIGN: This is a cross-sectional study using
      data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised
      controlled trial. SETTING: French community dwellers aged 70 or over reporting
      subjective memory complaints, but free from a diagnosis of clinical dementia.
      PARTICIPANTS: Individuals were from the MAPT trial (n = 177) with data on total
      plasma homocysteine at baseline and cortical Abeta load. MEASUREMENTS: Cortical
      to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir
      positron emission tomography (PET). Total baseline plasma homocysteine was
      measured using an enzymatic cycling assay. Baseline omega 3 index was measured
      using gas chromatography. Cross-sectional associations were explored using
      adjusted multiple linear regression models. RESULTS: We found that total baseline
      plasma homocysteine was not significantly associated with cortical Abeta as
      demonstrated using multiple linear regression models adjusted for age, sex,
      education, cognitive status, time interval between baseline and PET-scan, omega-3
      index, MAPT group allocation and Apolipoprotein E epsilon4 status (B-coefficient 
      0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that
      homocysteine was however significantly associated with cortical Abeta in subjects
      with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E
      epsilon4 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10),
      but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95
      % CI: -0.023,0.003, p = 0.132, n = 66). CONCLUSIONS: The role of n-3 PUFAs on the
      relationship between homocysteine and cerebral Abeta warrants further
      investigation.

PMID- 29188864
TI  - Development of a Novel Six-Month Nutrition Intervention for a Randomized Trial in
      Older Men with Mobility Limitations.
AB  - OBJECTIVES: Nutrition impacts the development of sarcopenia and protein intake is
      an important modulator of skeletal muscle mass loss in older people. The
      Optimizing Protein Intake in Older Men with Mobility Limitation (OPTIMEN) Trial
      was designed to assess the independent and combined effects of higher protein
      intake and a promyogenic agent, testosterone, on lean body mass, muscle strength
      and physical function in older men with mobility disability. The purpose of this
      paper is to describe the experimental design and nutrition intervention,
      including techniques used by research dietitians to develop and deliver energy
      and protein-specific meals to the homes of community-dwelling participants.
      Strategies to enhance long-term dietary compliance are detailed. DESIGN:
      Randomized, double-blind, placebo-controlled six-month intervention trial.
      SETTING: Participants were recruited from Boston MA USA and surrounding
      communities. PARTICIPANTS: Older men who were mobility-limited (Short Physical
      Performance Battery (SPPB) 3-10) and consuming less protein (<0.83 g/kg/day) were
      recruited for this study. INTERVENTION: Here we report the successful
      implementation of a double-blind, placebo-controlled, parallel group, randomized
      controlled trial with a 6-month intervention period among community-living men,
      age 65 years and older with a mobility limitation. A controlled feeding plan was
      used to deliver required energy intakes and prescribed protein quantities of 0.8
      or 1.3 grams/kilogram/day (g/kg/d) in three meals plus snacks and supplements. A
      2x2 factorial design was used to assess the effects of protein level alone and in
      combination with testosterone (vs. placebo) on changes in lean body mass (primary
      outcome), muscle strength, and physical function. RESULTS: A total of 154 men met
      the eligibility criteria; 112 completed a 2-week run-in period designed to
      evaluate compliance with the nutrition intervention. Of these, 92 subjects met
      compliance eligibility criteria and agreed to be randomized; 85% completed the
      full trial. The study successfully delivered three meals per day to subjects,
      with a high degree of compliance and subject satisfaction. Overall self-reported
      compliance rates were 80% and 93% for the meals and supplements, respectively.
      Details of compliance strategies are discussed. CONCLUSION: This community-based
      study design may serve as a model for longer-term nutritional interventions
      requiring monitoring of dietary compliance in a home-based feeding and
      supplementation trial.

PMID- 29188865
TI  - Dietary Diversity and Cognitive Function among Elderly People: A Population-Based
      Study.
AB  - OBJECTIVES: To explore associations of dietary diversity with cognitive function
      among Chinese elderly. DESIGN: This cross-sectional study was conducted in 2011
      2012, data were analyzed using multiple linear regression and logistic regression
      models. SETTING: community-based setting in the 23 provinces in China. SUBJECTS:
      8,571 elderly participants, including 2984 younger elderly aged 65-79 and 5587
      oldest old aged 80+ participated in this study. MEASUREMENT: Intake frequencies
      of food groups was collected and dietary diversity (DD) was assessed based on the
      mean of DD score. Cognitive function was assessed using the Chinese version of
      Mini-Mental State Examination (MMSE), and cognitive impairment was defined using
      education-based cutoffs. Information about socio-demographics, lifestyles,
      resilience and health status was also collected. RESULTS: Poor dietary diversity
      was significantly associated with cognitive function, with beta (95% CI) of 
      0.11(-0.14, -0.08) for -log (31-MMSE score) and odds ratio (95% CI) of 1.29
      (1.14, 1.47) for cognitive impairment. Interaction effect of age with DD was
      observed on cognitive impairment (P interaction=0.018), but not on -log (31-MMSE
      score) (P interaction=0.08). Further separate analysis showed that poor DD was
      significantly associated with increased risk of cognitive impairment in the
      oldest old (p<0.01), with odds ratio (95% CI) of 1.34 (1.17, 1.54), while not in
      the younger elderly (p>0.05), with OR (95% CI) being 1.09 (0.80, 1.47) in the
      fully adjusted model. Similar results were obtained when DD was categorized into
      four groups. CONCLUSIONS: Poor dietary diversity was associated with worse global
      cognitive function among Chinese elderly, and particularly for the oldest old.
      This finding would be very meaningful for prevention of cognitive impairment.

PMID- 29188866
TI  - Alcohol Energy Intake Is Related to Low Body Mass Index in Japanese Older Adults:
      Data from the 2010-2011 National Health and Nutrition Survey.
AB  - OBJECTIVE: The objective of this study was to identify lifestyle and nutritional
      factors associated with low BMI in Japanese older adults, with a focus on alcohol
      energy intake. DESIGN: Cross-sectional study. PARTICIPANTS: Data from 1,093
      respondents (711 men and 382 women) to the National Health and Nutrition Survey
      aged 65 years and older were included in this study. MEASUREMENTS: Data were
      analyzed for associations between BMI and lifestyle, energy, and nutrient intake.
      Alcohol energy intake was calculated from total energy and participants were
      categorized into BMI quartiles. Energy-adjusted nutrient intakes were calculated
      as residuals from a regression model, with BMI as the independent variable and
      lifestyle factors and nutrient intake as dependent variables. Between-BMI
      quartile differences were assessed for each sex using multivariate logistic
      regression analysis. In addition, the nutrient intakes of men consuming more than
      280 kcal and less than 280 kcal of alcohol energy per day were compared. RESULTS:
      Men and women in the lowest BMI quartile had lower total energy intake but higher
      alcohol energy intake than men in the other BMI quartiles. In multivariate
      logistic regression analysis, the lowest BMI quartile was associated with total
      energy (OR: 0.81, p = 0.0310) and alcohol energy intake (OR: 1.22, p = 0.0472) in
      men. In men, protein, carbohydrate, fat, calcium, iron, and vitamin intakes were
      less in those that consumed >= 280 kcal than in those that consumed < 280 kcal of
      alcohol per day. CONCLUSION: Our results demonstrate an association between
      alcohol energy intake and low BMI in older Japanese individuals.

PMID- 29188867
TI  - High Free Fatty Acid Levels Are Associated with Stroke Recurrence and Poor
      Functional Outcome in Chinese Patients with Ischemic Stroke.
AB  - BACKGROUND: The aim of this study is to investigate whether serum and
      cerebrospinal fluid (CSF) free fatty acid (FFA) levels are associated with
      outcome and recurrence in a cohort of patients with an acute ischemic stroke
      (AIS). METHODS: From December 2013 to May 2015, patients with first-ever AIS were
      included. FFA level and NIH stroke scale (NIHSS) were measured at the time of
      admission. Logistic regression analysis was used to evaluate the stroke outcome
      and recurrence according to FFA level. Clinical follow-up was performed at 6
      month. RESULTS: In our study, we studied 296 patients (52.7% male). We have found
      a positive correlation between serum and CSF levels of FFA. Patients with a poor
      outcome and recurrence had significantly increased FFA serum and CSF levels on
      admission (all p<0.0001). Multivariate logistic regression analysis adjusted for
      common risk factors showed that FFA was an independent predictor of poor
      functional outcome and recurrence. Odds ratios (OR) values were more significant
      for the higher levels of FFA. CONCLUSION: In summary, baseline serum and CSF FFA
      level were associated with stroke poor function outcome and recurrence,
      suggesting an effect of FFA on disease course in AIS.

PMID- 29188868
TI  - Vitamin D Deficiency and Insufficiency Prevalence in the West of Ireland - A
      Retrospective Study.
AB  - OBJECTIVES: Vitamin D plays an important role in calcium homeostasis and is
      essential for normal bone growth and remodeling. Previous studies of acutely ill
      and institutionalized older women in Galway revealed that vitamin D insufficiency
      is extremely common. We aimed to evaluate age and gender-related rates of vitamin
      D insufficiency and deficiency in adult patients attending their General
      Practitioners in the same region. DESIGN: A retrospective cohort study. SETTING:
      General practices in Galway, a city located on the west coast of Ireland,
      latitude 53.17 North. PARTICIPANTS: A total of 15,708 consecutive blood samples
      from adults attending their General Practitioners between January 2013 and
      December 2014 were sent to the Clinical Biochemistry Laboratory in the University
      Hospital Galway for vitamin D level testing. 73% were from women. INTERVENTION:
      Data were collected and grouped according to age, sex and season. Vitamin D
      levels (25OHD) were categorised into deficiency (<25nmol/L), insufficiency (25
      50nmol/L) and sufficiency ( >50nmol/L). MEASUREMENTS: Median and interquartile
      range were reported as vitamin D levels were not normally distributed.
      Descriptive statistics were performed using STATA/MP 13.1 for Mac. RESULTS: While
      vitamin D levels were sufficient in 56.4% (n=8,496), they were insufficient in
      32.4% (n=4,891) and deficient in 11.2% (n=1,691). Of the deficient group, 19%(
      325) had levels <15nmol/L consistent with profound deficiency. Men were more
      likely than women to be deficient (12% (n=489) vs. 10.9% (n=1,202)) and
      insufficient (38.0% (n=1,550) vs. 30.4% (n=3,341)) (p<0.01). Highest rates of
      deficiency were seen in those 81-97 years (19.4% (n=136)) and 18-40 years (13.8%
      (n=543)), the former group showing less seasonal variation. CONCLUSION: Overall
      prevalence of insufficiency is similar to those in national and European studies
      published recently. However, there is a high possibility that those most
      vulnerable to vitamin D deficiency were underrepresented in this cohort, when
      results from previous studies in the same region are considered. Further
      prospective studies are needed to guide treatment with supplementation of vitamin
      D for appropriate subgroups.

PMID- 29188869
TI  - Changes in Lean Mass and Serum Myostatin with Habitual Protein Intake and High
      Velocity Resistance Training.
AB  - OBJECTIVES: Examine the associations between dietary protein intake, lean mass
      (LM), and serum myostatin (Mstn) levels among community-dwelling older adults
      participating in a 20-week high-velocity resistance training (HVRT) program.
      DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study consisted of 33
      community-dwelling, older adults (mean age 77.0 years, SD = 6.4); all of which
      obtained physician clearance prior to study participation. MEASUREMENTS: Twenty
      five females and eight males were randomized to a control (CON) or HVRT group.
      Anthropometric measures were obtained via dual energy x-ray absorptiometry (DXA)
      and peripheral venous blood draw used for serum myostatin analysis. Exercise was
      performed twice per week for 20 consecutive weeks. Food intake estimation with a
      diet history questionnaire (DHQ) was used for protein intake comparison to the
      recommended dietary allowance (RDA). All measures were recorded both prior to and
      following study participation. RESULTS: Altogether, protein was consumed in
      amounts more generous (1.01 +/- 0.47 g.kg-1.d-1) than that of the RDA (0.8 g.kg
      1.d-1). As a result of significant LM differences among men and women (p < 0.01),
      additional data were analyzed specific to sex. Serum myostatin was greater among
      females (6681.8 +/- 3155.0 pg.mL-1) than males (5560.0 +/- 2946.1 pg.mL-1);
      however, these values were not significantly different (p = 0.39). Combined,
      protein consumption and serum myostatin did not significantly influence LM among
      males (p = 0.09) or females (p = 0.71). Irrespective of training group,
      significant changes were not exhibited in dietary intake patterns, LM, or serum
      myostatin. CONCLUSIONS: Contrary to the proposed hypothesis, results suggest
      protein consumption and circulating serum myostatin levels did not significantly
      influence LM among older adults. Although HVRT positively impacts LM, neither
      exercise group displayed significant changes in LM. Therefore, further research
      is needed examining dietary intake, exercise modality, and myostatin
      downregulation as non-pharmacological approaches to combating sarcopenia.

PMID- 29188870
TI  - Association between Siesta (Daytime Sleep), Dietary Patterns and the Presence of
      Metabolic Syndrome in Elderly Living in Mediterranean Area (Medis Study): The
      Moderating Effect of Gender.
AB  - OBJECTIVES: Several lifestyle parameters including diet, physical activity and
      sleep were associated in isolation with the presence of Metabolic Syndrome (MetS)
      in adults, to date there is a paucity of studies which evaluated their combined
      role aging populations and especially with respect to gender. Therefore, the aim
      of the present study was to provide a global consideration of the lifestyle
      factors associated with MetS among elderly individuals. DESIGN: Cross-sectional
      observational study. SETTING: 21 Mediterranean islands and the rural Mani region
      (Peloponnesus) of Greece. PARTICIPANTS: during 2005-2015, 2749 older (aged 65-100
      years) from were voluntarily enrolled in the study. MEASUREMENTS: Dietary habits,
      energy intake, physical activity status, socio-demographic characteristics,
      lifestyle parameters (sleeping and smoking habits) and clinical profile aspects
      were derived through standard procedures. The presence of MetS was defined using
      the definition provided by NCEP ATP III (revised) and cluster analysis was used
      to identify overall dietary habit patterns. RESULTS: The overall prevalence of
      MetS in the study sample was 36.2%, but occurred more frequently in females
      (40.0% vs. 31.8%, respectively, p=0.03). Individuals with MetS were more likely
      to sleep during the day (89.4% vs. 76.8% respectively, p=0.039) and frequent
      'siesta' was positively linked to the odds of MetS presence in females (Odds
      Ratio (OR) =3.43, 95% Confidence Intervals (CI): 1.08-10.9), but not for men
      (p=0.999). The lower carbohydrate (i.e., 45.2% of total daily energy, 120+/
      16gr/day) dietary cluster was inversely associated with the odds for MetS
      presence, but only for men (OR=0.094, 95%CI: 0.010-0.883). CONCLUSIONS: Lifestyle
      parameters including sleep and diet quality are strongly associated with the
      presence of MetS in elderly cohort, but different their level of influence
      appears to be different, depending on gender. Further research is needed to
      better consider the role of lifestyle characteristics in the management of MetS
      in clinical practice.

PMID- 29188871
TI  - Impact of Age on the Association Between Body Mass Index and All-Cause Mortality
      in Patients with Atrial Fibrillation.
AB  - OBJECTIVES: To explore the impact of age on the association between body mass
      index (BMI) and all-cause mortality in patients with atrial fibrillation (AF).
      METHODS: A total of 1991 patients with AF (69 +/- 13 years, 54.9% female) were
      divided into three age groups: < 65 years, 65-75 years, and > 75 years, and
      followed for one year. The primary outcome was defined as all-cause mortality,
      with secondary outcomes including thromboembolism and major bleeding. Cox
      regression models were utilized to estimate hazard ratios (HRs) and 95%
      confidence intervals (CIs). RESULTS: Compared to patients aged < 65 years, elder
      groups had much lower BMI and more comorbidities other than a lower prevalence of
      valvular heart disease. During one-year follow-up, 277 (13.9%) patients died, 158
      (7.9%) underwent thromboembolism events and 26 (1.3%) had major bleeding.
      Mortality and thromboembolism risk were both notably higher in patients with
      advanced age (all P values < 0.001). Using normal weight patients as reference,
      mortality risk was significantly lower in overweight (HR 0.548; 95% CI 0.404
      0.744) and obese patients (HR 0.536; 95% CI 0.325-0.883) for the entire cohort,
      with reduced death risk mainly observed in overweight patients aged 65-75 years
      (HR 0.285; 95% CI 0.131-0.621) and aged > 75 years (HR 0.686; 95% CI 0.473
      0.993), but not in patients aged < 65 years. Continuous analyses of BMI indicated
      consistent results. CONCLUSION: High BMI is associated with reduced mortality
      rate in patients with AF, and this association is affected by age, with the so
      called "obesity paradox" confined to those with advanced age rather than young
      patients.

PMID- 29188872
TI  - Soluble Milk Proteins Improve Muscle Mass Recovery after Immobilization-Induced
      Muscle Atrophy in Old Rats but Do not Improve Muscle Functional Property
      Restoration.
AB  - OBJECTIVES: Effect of 3 different dairy protein sources on the recovery of muscle
      function after limb immobilization in old rats. DESIGN: Longitudinal animal
      study. SETTING: Institut National de la Recherche Agronomique (INRA). The study
      took part in a laboratory setting. INTERVENTION: Old rats were subjected to
      unilateral hindlimb immobilization for 8 days and then allowed to recover with 3
      different dietary proteins: casein, soluble milk proteins or whey proteins for 49
      days. MEASUREMENTS: Body weight, muscle mass, muscle fibre size, isometric,
      isokinetic torque, muscle fatigability and muscle oxidative status were measured
      before and at the end of the immobilization period and during the recovery period
      i.e 7, 21, 35 and 49 days post immobilization. RESULTS: In contrast to the casein
      diet, soluble milk proteins and whey proteins were efficient to favor muscle mass
      recovery after cast immobilization during aging. By contrast, none of the 3 diary
      proteins was able to improve muscle strength, power and fatigability showing a
      discrepancy between the recovery of muscle mass and function. However, the
      soluble milk proteins allowed a better oxidative capacity in skeletal muscle
      during the rehabilitation period. CONCLUSION: Whey proteins and soluble milk
      proteins improve muscle mass recovery after immobilization-induced muscle atrophy
      in old rats but do not allow muscle functional property restoration.

PMID- 29188873
TI  - p49/STRAP, a Serum Response Factor Binding Protein (SRFBP1), Is Involved in the
      Redistribution of Cytoskeletal F-Actin Proteins during Glucose Deprivation.
AB  - The functional decline that usually accompanies adult aging also encompasses
      cellular changes including cytoplasmic architecture. In addition to their role in
      cytoskeletal structure, actin microfilaments have important roles in various
      cellular processes, including cell-to-cell communication and intracellular
      signaling. Age-related diseases and late-stage cellular morphological appearances
      often correlate with altered f-actin structure, which has been observed most
      notably in cancer. What remains less clear are the molecular pathways that may be
      involved in normal and premature aging-induced f-actin changes. We report herein
      that p49/STRAP, a serum response factor binding protein (SRFBP1), is increased
      with normal aging and appears to be sensitive to low glucose-exposure. Our study
      results suggest that increased levels of p49/STRAP expression tend to correlate
      with f-actin redistribution genes, particularly cofilin, while siRNA-mediated
      knockdown of p49/STRAP resulted in a reduction of thymosin-beta4. Furthermore,
      with the redistribution of f-actin, we observed an increase in the intermediate
      filament vimentin, compatible with the notion that vimentin may be increased due
      to its greater role in cytoskeletal dynamics during advancing population doubling
      levels (PDLs) and in response to a low-glucose exposure. Taken together, these
      data suggest that p49/STRAP may play a role in glucose-deprivation associated
      cytoskeletal changes.

PMID- 29188874
TI  - Blood Pressure Is Associated with Tea Consumption: A Cross-sectional Study in a
      Rural, Elderly Population of Jiangsu China.
AB  - OBJECTIVES: Tea has long been hypothesized to possess hypotensive effects.
      However, there is uncertainty regarding the association of tea consumption with
      arterial blood pressure (BP). We aimed to examine the association between tea
      consumption and BP components including systolic BP (SBP) and diastolic BP (DBP).
      DESIGN: Community-based, cross-sectional study of Suzhou City, Jiangsu Province,
      China. SETTING: Tea consumption has protective influence on BP and presence of
      hypertension. PARTICIPANTS: 4579 older adults aged 60 years or older from the
      Weitang Geriatric Diseases study. MEASUREMENTS: Detailed information regarding
      tea consumption was collected using a pre-designed questionnaire. BP components
      were measured at least 3 times with a minimum 5-minute interval, by well-trained
      research nurses. METHODS: Data of 4579 older adults (response rate: 82%) aged 60
      years or older from the Weitang Geriatric Diseases study were included in the
      analysis and we estimated the relationship of tea consumption and BP using linear
      regression models and the association between tea consumption and risk of
      hypertension using logistic regression models. RESULTS: In linear regression
      models, higher tea consumption frequency was found to be associated with lower
      systolic BP values, after adjusting for the effect of age, sex, education level,
      lifestyle-related factors, and cardiometabolic confounding factors in overall
      (coefficient =-1.49, P=0.0003), normotensive (coefficient =-0.91, P=0.017) and
      participants without anti-hypertensive treatment (coefficient =-1.26, P=0.027).
      Significant inverse association between diastolic BP and frequency of tea
      consumption was also observed in the overall subjects (coefficient =-0.74,
      P=0.003). In multivariate logistic analyses, habitual tea drinking was inversely
      associated with presence of hypertension [odds ratio (OR)=0.79, P=0.011] , and
      there was a progressive reduction in risk associated with higher frequency of tea
      consumption (P for trend=0.011). CONCLUSION: Habitual tea consumption was found
      to be associated with lower values of components of BP and a reduced likelihood
      of having hypertension in older adults. Given the widespread consumption of tea
      throughout China and the world, together with the major cardiovascular disease
      risk, our findings have important implications for human health.

PMID- 29188877
TI  - Vitamin D Status and Elevated Red Cell Distribution Width in Community-Dwelling
      Adults: Results from the National Health and Nutrition Examination Survey 2001
      2006.
AB  - OBJECTIVES: Elevated red cell distribution width (RDW) is associated with
      morbidity and mortality in community-dwelling individuals. Although RDW is
      traditionally used to diagnose anemia, it may also be a marker of systemic
      inflammation. Since vitamin D is a potent modulator of inflammatory cytokines our
      goal was to investigate whether 25-hydroxyvitamin D levels (25OHD) are associated
      with RDW in non-hospitalized adults. DESIGN: To investigate this association, we
      conducted a cross-sectional study. Stepwise multivariable linear and logistic
      regression models were used to assess the independent association of 25OHD with
      RDW. Elevated RDW was defined as >14.5%. SETTING: Nationwide sample of non
      hospitalized adults within the United States. PARTICIPANTS: Individuals from the
      National Health and Nutrition Examination Survey from 2001-2006. RESULTS: 15,162
      individuals comprised the analytic cohort. Mean 25OHD was 24.9 ng/mL (SE 0.4) and
      the prevalence of elevated RDW was 6.3%. Linear regression analysis, controlling
      for age, sex, race, mean corpuscular volume, albumin, and neutropenia,
      demonstrated that 25OHD was inversely associated with RDW (beta=-0.01; 95%CI 
      0.01 to -0.01). Logistic regression analysis, controlling for the same
      covariates, also demonstrated an inverse association of 25OHD with elevated RDW
      (OR 0.96; 95%CI 0.94-0.99). Individuals with 25OHD <30 ng/mL were more likely to
      have elevated RDW (OR 1.65; 95%CI 1.13-2.40) compared to those individuals with
      levels >=30ng/mL. CONCLUSIONS: In a nationwide sample of non-hospitalized adults
      within the United States, low 25OHD was associated with increased likelihood of
      elevated RDW. Further studies are needed to determine whether optimizing vitamin
      D status can reduce the prevalence of elevated RDW, and thereby reduce morbidity
      and mortality in the general population.

PMID- 29188875
TI  - Intake of a Protein-Enriched Milk and Effects on Muscle Mass and Strength. A 12
      Week Randomized Placebo Controlled Trial among Community-Dwelling Older Adults.
AB  - OBJECTIVES: To investigate the effect of 20 g protein with breakfast and evening
      meal on muscle mass, muscle strength and functional performance in older adults.
      DESIGN: A double-blinded randomized controlled study. SETTING: Oslo and Akershus
      University College of Applied Sciences, Norway. PARTICIPANTS: Healthy community
      dwelling men and women (>= 70 years) with reduced physical strength and/or
      performance. INTERVENTION: Subjects were randomly assigned to receive either
      protein-enriched milk (2 x 0.4 L/d; protein group) or an isocaloric carbohydrate
      drink (2 x 0.4 L/d; control group) with breakfast and evening meal for 12 weeks.
      MEASUREMENTS: The primary endpoints were muscle mass measured by dual X-ray
      absorptiometry, and tests of muscle strength (one repetition maximum test of
      chest press and leg press) and functional performance (handgrip strength, stair
      calimb and repeated chair rise). RESULTS: In total, 438 subjects were screened,
      50 subjects were randomized and 36 completed the study. Chest press improved
      significantly in the protein (1.3 kg (0.1-2.5), p=0.03) and the control group
      (1.5 kg (0.0-3.0), p=0.048), but with no difference between the groups (p=0.85).
      No significant change in leg press (p=0.93) or muscle mass (p=0.54) were observed
      between the protein and the control group. Nor did we observe any significant
      differences in the functional performance tests (p>0.05 for all tests) between
      the groups. CONCLUSION: Increased protein intake (2 x 20 g/d) did not
      significantly improve muscle mass, muscle strength or functional performance in
      healthy older weight stable adults. Whether intake of > 20 g protein to each meal
      is necessary for preservation of muscle mass and strength in older adults should
      be further investigated in a larger study. This underscores the need for well
      designed studies that can differentiate between the effect of protein intake and
      increased energy. This trial was registered at Clinicaltrials.gov (ID no.
      NCT02218333).

PMID- 29188876
TI  - Association of Cortical beta-Amyloid with Erythrocyte Membrane Monounsaturated
      and Saturated Fatty Acids in Older Adults at Risk of Dementia.
AB  - OBJECTIVES: We examined the relationships between erythrocyte membrane
      monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs) and cortical
      beta-amyloid (Abeta) load in older adults reporting subjective memory complaints.
      DESIGN: This is a cross-sectional study using data from the Multidomain Alzheimer
      Preventive Trial (MAPT); a randomised controlled trial. SETTING: French community
      dwellers aged 70 or over reporting subjective memory complaints, but free from a
      diagnosis of clinical dementia. PARTICIPANTS: Participants of this study were 61
      individuals from the placebo arm of the MAPT trial with data on erythrocyte
      membrane fatty acid levels and cortical Abeta load. MEASUREMENTS: Cortical-to
      cerebellar standard uptake value ratios were assessed using [18F] florbetapir
      positron emission tomography (PET). Fatty acids were measured in erythrocyte cell
      membranes using gas chromatography. Associations between erythrocyte membrane
      MUFAs and SFAs and cortical Abeta load were explored using adjusted multiple
      linear regression models and were considered significant at p <= 0.005 (10
      comparisons) after correction for multiple testing. RESULTS: We found no
      significant associations between fatty acids and cortical Abeta load using
      multiple linear regression adjusted for age, sex, education, cognition, PET-scan
      to clinical assessment interval, PET-scan to blood collection interval and
      apolipoprotein E (ApoE) status. The association closest to significance was that
      between erythrocyte membrane stearic acid and Abeta (B-coefficient 0.03, 95 % CI:
      0.00,0.05, p = 0.05). This association, although statistically non-significant,
      appeared to be stronger amongst ApoE epsilon4 carriers (B-coefficient 0.04, 95 %
      CI: -0.01,0.09, p = 0.08) compared to ApoE epsilon4 non-carriers (B-coefficient
      0.02, 95 % CI: -0.01,0.05, p = 0.18) in age and sex stratified analysis.
      CONCLUSION: Future research in the form of large longitudinal observational study
      is needed to validate our findings, particularly regarding the potential
      association of stearic acid with cortical Abeta.

PMID- 29188878
TI  - Effect of a 6-Month Brisk Walking Program on Walking Endurance in Sedentary and
      Physically Deconditioned Women Aged 60 or Older: A Randomized Trial.
AB  - BACKGROUND: Walking endurance is a predictor of healthy ageing. OBJECTIVE: To
      examine if a 6-month brisk walking program can increase walking endurance in
      sedentary and physically deconditioned older women. TRIAL DESIGN: Randomized
      controlled trial. SETTING: Women recruited from public meetings aimed at
      promoting physical activity in women aged 60 or older. SUBJECTS: 121 women aged
      65.7 +/- 4.3 years, with sedentary lifestyle (Physical Activity Questionnaire for
      the Elderly score < 9.4), and a 6-minute walking distance (6MWD) below normal
      value based on their gender, age, and body weight, and weight. METHODS: Women
      were randomly assigned to a 150 min/week brisk walking program (two supervised
      sessions and one session on their own per week) for six months (exercisers)
      (n=61) or a control group with physical activity allowed freely (n=60). OUTCOME:
      The primary outcome was relative change in 6MWD. RESULTS: 54/61 exercisers and
      55/60 control subjects completed the program and data analysis was possible for
      51 exercisers and 47 controls. At baseline, 6MWD was on average 23.1% and 22.5%
      below age-matched norms in exercisers and controls, respectively. Attendance rate
      for supervised sessions was 92% in exercisers. The 6MWD increased more
      significantly in exercisers than in controls (mean increase of 41.5% vs 11.0 %;
      p<0.0001). Over the 6-month program, 38 exercisers (74.5%) vs 5 controls (10.6%)
      had a 6MWD over the age-matched norm (p<0.0001). Exercisers with the highest
      tertile of 6MWD improvement (>46%) were those with baseline lowest values of 6MWD
      (p=0.001) and highest values of body mass index (BMI) (p<0.01). CONCLUSION:
      Present results support recommendation that brisk walking programs should be
      encouraged to improve walking endurance in physically deconditioned women aged 60
      or older, especially in those with high BMI.

PMID- 29188879
TI  - Racial Differences in Eating Patterns and Food Purchasing Behaviors among Urban
      Older Women.
AB  - OBJECTIVE: To examine differences in diet and food purchasing behaviors between
      Black and White older women living in urban neighborhoods. DESIGN: Cross
      sectional observational study. SETTING: Urban neighborhoods in Washington, DC,
      USA. PARTICIPANTS: Community-dwelling White and Black women of age 65 and older.
      MEASUREMENTS: Participants were queried on diet via 24-hour recalls, food
      purchasing habits, their use of neighborhood resources and local travel patterns.
      Frequency and location of self-reported food purchasing and consumption were
      compared by race. RESULTS: In 2014 and 2015, 49 White and 44 Black older women
      were enrolled in the study. Compared to Whites, Blacks reported lower daily
      caloric intake (mean (SD) 1314 (404) vs. 1529 (448), p=0.02), with a higher
      percent of calories from protein and fat 1.8 (7.0), p=0.03), and a slightly
      higher polyunsaturated to saturated fat ratio (p=0.05). Blacks had substantially
      lower alternate healthy eating index (AHEI) (33.5 (10.2) vs. 43.9 (10.8) of 80
      possible points, p<0.001), daily intake (grams) of total fiber (15.3 (8.1) vs.
      22.9 (8.5), p<0.001), insoluble fiber (10.8 (6.9) vs. 15.9 (6.5), p<0.001), and
      soluble fiber (4.5 (2.0) vs. 6.9 (2.8), p<0.001). Blacks had lower intake of
      micronutrients, alcohol and caffeine. Blacks shopped for groceries less often
      (4.4 (3.0) vs. 6.2 (3.0) monthly; p=0.006) and spent a longer time traveling to
      stores (15.8 (9.1) vs. 11.5 (7.2) minutes per trip, p=0.02). A lower percent of
      Blacks walked to stores (14% vs. 40%, p=0.003) and a higher percent of Blacks
      rode in a car with someone else (33% vs. 6%, p<0.001). CONCLUSIONS: In an urban
      setting, food consumption and purchasing behaviors differed substantially between
      older Black and White women, which should be further investigated and considered
      to promote healthy eating in older populations.

PMID- 29188880
TI  - Perspectives on the Causes of Undernutrition of Community-Dwelling Older Adults:
      A Qualitative Study.
AB  - OBJECTIVES: Undernutrition is a major health concern particularly in vulnerable
      older adults. The present study aimed to reveal the causes of undernutrition as
      reported by community-dwelling older adults. DESIGN: Twenty-five semi-structured
      interviews and two focus group discussions were performed and analyzed. SETTING:
      Community-dwelling. PARTICIPANTS: Older adults. MEASUREMENTS: A questionnaire on
      demographics, Short Nutritional Assessment Questionnaire 65+ and interviews on
      the potential causes of undernutrition. RESULTS: 33 older adults agreed to
      participate in the interviews and focus groups. Our findings indicate that a wide
      variety of causes of undernutrition, both modifiable and non-modifiable, were
      mentioned by the older adults. Many modifiable causes of undernutrition were
      reported in the mental, social or food and appetite theme, such as poor food
      quality provided by meal services, the inability to do groceries, loneliness and
      mourning. Non-modifiable causes included, forgetfulness, aging, surgery and
      hospitalization. CONCLUSIONS: This study provides guidance to better understand
      the underlying causes of undernutrition from an older adult's perspective. The
      modifiable causes provide specific direction towards practical implications that
      might decrease or prevent undernutrition. Non-modifiable causes should raise
      awareness of an increased risk of undernutrition by health professionals in
      primary and secondary care, caregivers and family members.

PMID- 29188881
TI  - Malnutrition in Acutely Unwell Hospitalized Elderly - "The Skeletons Are Still
      Rattling in the Hospital Closet".
AB  - INTRODUCTION: Malnutrition is common in hospitalized patients with prevalence
      rates of up to 30% in Australian hospitals with adverse consequences for both the
      patients and health care services. Despite formulation of nutritional screening
      protocols, not all hospitalized patients get nutritional screening. Real life
      screening rates of hospitalized elderly patients are unknown. AIM: The present
      study explored nutrition screening rate in acutely unwell elderly patients
      admitted in a large tertiary hospital and how these patients fared depending upon
      their nutrition status. METHODS: A prospective cross-sectional study involving
      205 general medical patients >=60years recruited between November 2014 and
      November 2015. The number of patients who missed nutrition screening were noted
      and all patients underwent nutritional assessment by a qualified dietitian using
      PG-SGA and quality of life was measured using EQ-5D 5L. A survival curve was
      plotted and multivariate cox proportional hazard model was used to adjust for
      confounders. RESULTS: Only 99 (49.7%) patients underwent nutritional screening.
      One hundred and six (53.5%) patients were confirmed as malnourished by PG-SGA.
      Malnourished patients had significantly longer length of hospital stay and had
      worse quality of life. Mortality was significantly higher in malnourished
      patients at one year (23 (21.7%) vs 4 (4.3%); p<0.001) and cox proportional
      hazard model suggests that malnutrition significantly affects survival even after
      adjustment for confounders like age, sex, Charlson index and polypharmacy.
      CONCLUSION: This study confirms that nutrition screening is still suboptimal in
      elderly hospitalized patients with adverse consequences and suggests need for
      review of policies to improve screening practices.

PMID- 29188882
TI  - Nutrient Intake During Diet-Induced Weight Loss and Exercise Interventions in a
      Randomized Trial in Older Overweight and Obese Adults.
AB  - OBJECTIVES: Dietary restriction in obese older adults undergoing weight loss may
      exacerbate nutrient deficiencies common in this group; the nutritional health of
      older adults is a factor in their quality of life, disability, and mortality.
      This study examined the effect of an 18-month weight loss program based in social
      cognitive theory incorporating partial meal replacements, on nutrient intake in
      older overweight and obese adults. DESIGN: The following analysis is from the
      Intensive Diet and Exercise for Arthritis (IDEA) trial, a single-blind,
      randomized controlled trial. Individuals were randomized into one of three 18
      month interventions: exercise (E); intensive diet-induced weight loss (D); or
      intensive diet-induced weight loss plus exercise (D+E). SETTING: The study
      setting was at a university research facility. PARTICIPANTS: Overweight and obese
      older adults (n=388; BMI=33.7+/-3.8 kg/m2; 65.8+/-6.1 years) were recruited.
      INTERVENTIONS: The D and D+E interventions (group mean goal of >=10% loss by 18
      months) utilized partial meal replacements (2 meal replacement shakes/day for 6
      months). Exercise training for E and D+E was 3 days/week, 60 minutes/day.
      MEASUREMENTS: Three day food records were collected at baseline, 6-months, and 18
      months and analyzed for total energy and macro- and micronutrient intake.
      Comparisons of dietary intake among treatment groups were performed at 6 and 18
      months using mixed linear models. RESULTS: Weight loss at 18-months was 11.3+/
      8.3% (D), 10.3+/-6.8% (D+E), and 1.2+/-4.2% (E). Meal replacements were used by
      more than 60% (6-months) and 50% (18-months) of D and D+E participants, compared
      to <=15% for E. Both D and D+E consumed less energy and fat, and more
      carbohydrates and selected micronutrients than E during follow-up. More than 50%
      of all participants consumed less than the recommended intake of particular
      vitamins and minerals. CONCLUSIONS: The diet intervention improved intakes of
      several nutrients. However, inadequate intake of several vitamins and minerals of
      concern for older adults suggests they need further guidance to assure adequate
      intake.

PMID- 29188883
TI  - Dietary Approach to Stop Hypertension with Sodium Reduction for Chinese Canadians
      (DASHNa-CC): A Pilot Randomized Controlled Trial.
AB  - BACKGROUND: There is a lack of culturally sensitive dietary interventions
      targeting Chinese Canadians despite unhealthy dietary behaviours being identified
      as the most important modifiable risk factor for hypertension in the Chinese
      population. AIMS: To determine the feasibility of a culturally sensitive dietary
      intervention for hypertension control; to examine the potential effects of the
      intervention on blood pressure and health-related quality of life among Chinese
      Canadians in community. METHODS: This study was a two-group pilot randomized
      controlled trial with 8 weeks follow up. Sixty self-identified Chinese Canadians,
      older than 45 years old and with grade one hypertension but not on
      antihypertensive medications were recruited in community. The control group
      received usual care and the intervention group received usual care plus newly
      developed DASHNa-CC intervention. The DASHNa-CC intervention consisted of a
      written manual, two classroom sessions, and one telephone booster call to provide
      healthy dietary and sodium reduction advice, integrated with Traditional Chinese
      Medicine food therapy recommendations for hypertension control. RESULTS: 618
      Chinese Canadians participated in blood pressure screening, and 60 eligible
      participants recruited. Participants were highly satisfied with the intervention
      and adhered to the trial protocol. The lost to follow-up rate was 5%. At 8 weeks
      post-randomization, those in the intervention group had greater reductions in
      systolic blood pressure [3.8mmHg, t (55) = -1.58, p = 0.12] and higher physical
      health scores [t (55) = 2.13, p = 0.04] compared to those of the control group.
      There were no group differences in health care utilization. CONCLUSIONS: It is
      feasible to deliver the DASHNa-CC intervention in a Chinese Canadian community.
      The DASHNa-CC intervention may decrease blood pressure and improve health-related
      quality of life for Chinese Canadians.

PMID- 29188884
TI  - Model Construction for Biological Age Based on a Cross-Sectional Study of a
      Healthy Chinese Han population.
AB  - OBJECTIVES: Biological age (BA) has been proposed to evaluate the aging status in
      an objective way instead of chronological age (CA). The purpose of our study is
      to construct a more precise formula of BA in the cross-sectional study based on a
      largest-ever sample of our studies. This formula aims at better evaluation of
      body function and exploring the disciplines of aging in different genders and age
      stages. METHODS: A total of 1,373 healthy Chinese Han (age range, 19-93 years)
      were recruited from five cities in China, including 581 males and 792 females.
      Physical examination, blood routine, blood chemistry, and other lab tests were
      performed to obtain a total of 74 clinical variables. Then, the principal
      component analysis (PCA) was used to select variables and estimate BA. The BA
      formula was further validated in a population with some diseases (n=266),
      including cardiovascular diseases, type 2 diabetes, kidney diseases, pulmonary
      diseases, cancer and disorders in nervous system. RESULTS: The BA formula was
      constructed as follows: BA = 0.358 (pulse pressure) + 0.258 (trail making test) -
      11.552 (mitral valve E/A peak) + 26.383 (minimum intima-media thickness) + 31.965
      (Cystatin C) + 0.163 (CA) - 3.902. In validation of the formula, BAs of patients
      were older than those of healthy persons. The BA accelerates faster in the middle
      aged population than in the elderly population (>75 years old). CONCLUSION: This
      BA formula can reflect health condition changes of aging better than CA in a
      Chinese Han population.

PMID- 29188885
TI  - Perceived Resources as a Predictor of Satisfaction with Food-Related Life among
      Chilean Elderly: An Approach with Generalized Linear Models.
AB  - OBJECTIVE: The main objective of this study is to show why perceived resources
      are a strong predictor of satisfaction with food-related life in Chilean older
      adults. Design, sampling and participants: A survey was conducted in rural and
      urban areas in 30 communes of the Maule Region with 785 participants over 60
      years of age who live in their own homes. The Satisfaction with Food-related Life
      (SWFL) scale was used. Generalized linear models (GLM) were used for the
      regression analysis. RESULTS: The results led to different considerations: First,
      older adults' perceived levels of resources are a good reflection of their actual
      levels of resources. Second, the individuals rated the sum of the perceived
      resources as 'highly important' to explain older adults' satisfaction with food
      related life. Third, SWFL was predicted by satisfaction with economic situation,
      family importance, quantity of domestic household goods and a relative health
      indicator. Fourth, older adults who believe they have more resources compared to
      others are more satisfied with their food-related life. Finally, Poisson and
      binomial logistic models showed that the sum of perceived resources significantly
      increased the prediction of SWFL. CONCLUSION: The main conclusion is that
      perceived personal resources are a strong predictor of SWFL in Chilean older
      adults.

PMID- 29188886
TI  - Effects of Body Mass Index on Parasympathetic Nervous System Reactivity and
      Recovery Following Orthostatic Stress.
AB  - Vagally mediated heart rate variability (vmHRV), defined as the beat-to-beat
      fluctuations in a heart series mediated by the vagus nerve, serves as a non
      invasive index of parasympathetic nervous system (PNS) activity. Lower resting
      state vmHRV is associated with greater body mass index (BMI), providing a
      psychophysiological pathway linking obesity with health and disease. However
      little research has been conducted to examine how BMI may influence PNS
      reactivity to orthostatic stress. The present study sought to explore this in a
      sample of 59 individuals (44 females, mean age = 24.37 years, age range 19-65
      years). VmHRV was measured throughout the 5-minute baseline (sitting),
      orthostatic (standing), and recovery (sitting) conditions. Individuals were
      stratified into low (BMI < 20), moderate (BMI 20-25), and high (BMI > 25) BMI
      groups. Results indicate that the high BMI group had a greater decrease in vmHRV
      from baseline to standing in comparison to the moderate BMI group. Furthermore,
      the low BMI group showed lower vmHRV during recovery compared to baseline,
      suggesting that these individuals did not fully recover from the standing
      position. Taken together, these results extend previous literature showing that
      those with low and high BMI can show different yet maladaptive patterns of vmHRV
      in response to orthostatic stress.

PMID- 29188887
TI  - The Influence of Age the BMI and All-Cause Mortality Association: A Meta
      Analysis.
AB  - OBJECTIVES: To assess BMI range with the lowest mortality for those aged <65
      years and those >=65 years, utilising cohort studies that spanned the entire
      adult age range. DESIGN: A two-stage random effects meta-analysis of studies that
      reported mortality in cohorts both >=65 years and <65 years. Setting /
      Participants: Community living adults aged >=65 and <65 years. RESULTS: Eight
      studies were included with a total of 370 416 subjects (306 340 aged <65 years;
      64 076 >=65 years). In the older age group, mortality risk increased at BMIs
      lower than 22 (BMI range 21.0-21.9: hazard ratio (HR) (95% confidence interval
      (CI)): 1.05 (1.03, 1.07)), which was not seen in younger adults. In the younger
      group, mortality increased from BMI range 28.0-28.9 (HR (95% CI): 1.13 (1.00,
      1.29)), but mortality did not tend to increase significantly in the older group
      at BMIs above 23. CONCLUSION: The recommended healthy weight range is appropriate
      for younger and middle aged adults but a higher BMI range should be recommended
      for older adults based on mortality.

PMID- 29188889
TI  - Vitamin B12 Intake and Related Biomarkers: Associations in a Dutch Elderly
      Population.
AB  - BACKGROUND: Vitamin B12 status is measured by four plasma/ serum biomarkers:
      total vitamin B12 (total B12), holotranscobalamin (holoTC), methylmalonic acid
      (MMA) and homocysteine (tHcy). Associations of B12 intake with holoTC and tHcy
      and associations between all four biomarkers have not been extensively studied. A
      better insight in these associations may contribute to an improved
      differentiation between vitamin B12 deficiency and a normal vitamin B12 status.
      OBJECTIVE: This study investigates associations between vitamin B12 intake and
      biomarkers and associations between biomarkers. DESIGN: In this cross-sectional
      observational study, levels of total B12, HoloTC, MMA and tHcy were determined in
      participants of the B-PROOF study: 2919 elderly people (>=65 years, with a mean
      age of 74.1 years, a mean BMI of 27.1 and 50% women) with elevated tHcy levels
      (>=12 umol/L). B12 intake was assessed in a subsample. We assessed the
      association between intake and status with multivariate regression analysis. We
      explored the dose-response association between B12 intake and biomarkers and the
      association of total B12 and holoTC with tHcy and MMA with restricted cubic
      spline plots. RESULTS: A doubling of B12 intake was associated with 9% higher
      total B12, 15% higher HoloTC, 9% lower MMA and 2% lower tHcy. Saturation of
      biomarkers occurs with dietary intakes of >5 MUg B12. Spline regression showed
      that levels of MMA and tHcy started to rise when vitamin B12 levels fall below
      330 pmol/L and with HoloTC levels below 100 pmol/L, with a sharp increase with
      levels of B12 and HoloTC below 220 and 50 pmol/L respectively. CONCLUSIONS: In
      this study we observed a significant association between vitamin B12 intake and
      vitamin B12 biomarkers and between the biomarkers. The observed inflections for
      total B12 and holoTC with MMA and tHcy could indicate cut-off levels for further
      testing for B12 deficiency and determining subclinical B12 deficiency.

PMID- 29188888
TI  - Late-Life Body Mass Index, Rapid Weight Loss, Apolipoprotein E epsilon4 and the
      Risk of Cognitive Decline and Incident Dementia.
AB  - OBJECTIVES: To examine the effect of late-life body mass index (BMI) and rapid
      weight loss on incident mild cognitive impairment (MCI) and Alzheimer's disease
      (AD). DESIGN: Prospective longitudinal cohort study. SETTING: National
      Alzheimer's Coordinating Center (NACC) Uniform Data Set, including 34 past and
      current National Institute on Aging-funded AD Centers across the United States.
      PARTICIPANTS: 6940 older adults (n=5061 normal cognition [NC]; n=1879 MCI).
      MEASUREMENTS: BMI (kg/m2) and modified Framingham Stroke Risk Profile (FSRP)
      score (sex, age, systolic blood pressure, anti-hypertension medication, diabetes
      mellitus, cigarette smoking, prevalent cardiovascular disease, atrial
      fibrillation) were assessed at baseline. Cognition and weight were assessed
      annually. RESULTS: Multivariable binary logistic regression, adjusting for age,
      sex, race, education, length of follow-up, and modified FSRP related late-life
      BMI to risk of diagnostic conversion from NC to MCI or AD and from MCI to AD.
      Secondary analyses related late-life BMI to diagnostic conversion in the presence
      of rapid weight loss (>5% decrease in 12 months) and apolipoprotein E (APOE)
      epsilon4. During a mean 3.8-year follow-up period, 12% of NC participants
      converted to MCI or AD and 49% of MCI participants converted to AD. Higher
      baseline BMI was associated with a reduced probability of diagnostic conversion,
      such that for each one-unit increase in baseline BMI there was a reduction in
      diagnostic conversion for both NC (OR=0.977, 95%CI 0.958-0.996, p=0.015) and MCI
      participants (OR=0.962, 95%CI 0.942-0.983, p<0.001). The protective effect of
      higher baseline BMI did not persist in the setting of rapid weight loss but did
      persist when adjusting for APOE epsilon4. CONCLUSIONS: Higher late-life BMI is
      associated with a lower risk of incident MCI and AD but is not protective in the
      presence of rapid weight loss.

PMID- 29188890
TI  - Iberian Cured-Ham Consumption Improves Endothelial Function in Healthy Subjects.
AB  - OBJECTIVES: Previous studies have shown that dietary components such as oleic
      acid or polyphenols exert beneficial effects on endothelium. We aimed to assess
      the impact of regular consumption of Iberian cured-ham (ICH) on endothelial
      function. DESIGN: An open-label, randomized controlled parallel study. SETTING:
      Volunteers recruited through advertisements at a hospital in Madrid, Spain.
      PARTICIPANTS: 102 Caucasian adults (76.8% females) aged 25-55 years, and free
      from cardiometabolic disease. INTERVENTION: Participants were randomized to an
      ICH-enriched ad libitum diet or an ad libitum diet without ICH for 6 weeks.
      Subjects in ICH group were randomly provided with either acorn- or mixed-fed ICH,
      and followed up for an additional 6-week period under their usual diet.
      MEASUREMENTS: Clinical parameters, biomarkers of endothelial function and
      oxidative stress, microvascular vasodilatory response to hyperemia and arterial
      stiffness were measured before and after the intervention. RESULTS: After 6
      weeks, a larger decrease in PAI-1 was observed in subjects consuming ICH compared
      to the Control group (-6.2+/-17.7 vs. 0.3+/-1.4 ng/ml; p=0.020). Similarly,
      microvascular vasodilatory response to hyperemia showed a significant increase
      (112.4+/-391.7 vs. -56.0+/-327.9%; p=0.007). However, neither oxidative stress,
      hemodynamic nor clinical parameters differed significantly over the study.
      Additionally, after stopping ICH consumption, improvements in PAI-1 remained for
      6 additional weeks with respect to baseline (p=0.006). CONCLUSION: The present
      study demonstrates, for the first time, that regular consumption of ICH improves
      endothelial function in healthy adults. Strategies aimed to preserve or improve
      the endothelial function may have implications in vascular aging beyond the
      prevention of the atherothrombotic disease.

PMID- 29188891
TI  - Intake of Fruit and Vegetables and the Incident Risk of Cognitive Disorders: A
      Systematic Review and Meta-Analysis of Cohort Studies.
AB  - OBJECTIVES: No quantitative assessment has been performed to specifically link
      the consumption of fruit and vegetables with the incident risk of cognitive
      disorders. METHODS: We searched the PubMed and the Embase databases (both from
      the inception to June 13th, 2016) for records that report the intake of fruit and
      vegetables and the risk of developing cognitive disorders (Alzheimer's disease,
      dementia, and cognitive decline/impairment). A generic inverse-variance method
      (random-effects model) was used to combine the relative risks (RRs) and 95%
      confidence intervals (CIs). To explore the potential sources of heterogeneity, we
      performed the subgroup and meta-regression analyses by pre-specified
      characteristics. RESULTS: We identified 6 cohorts involving a total of 21,175
      participants. The pooled analysis showed that consumption of fruit and vegetables
      was inversely associated with the incident risk of cognitive disorders, and the
      pooled RR (95% CI) was 0.74 (0.62, 0.88), with evidence of significant
      heterogeneity (I2 =68%). Furthermore, we found that the significant heterogeneity
      might be attributed to the ethnic difference. CONCLUSION: Further large
      prospective studies should be performed to quantify the potential dose-response
      patterns of fruit and/or vegetables intake and to explore the role of fruit or
      vegetables consumption separately on cognitive disorders in different
      populations.

PMID- 29188892
TI  - Dyslipidemia as a Potential Moderator of the Association between Hearing Loss and
      Depressive Symptoms.
AB  - OBJECTIVES: Knowledge about moderation of the association between hearing loss
      and depression is scant. We investigated dyslipidemia as a potential moderator of
      the association between hearing/hearing loss and depressive symptoms. DESIGN:
      Cross-sectional study. SETTING: General population-based cohort in France
      (SU.VI.MAX 2; 2007-2009). PARTICIPANTS: N= 4,307 adults (mean age = 61.5 +/- 6.1
      y; 59.6% women). MEASUREMENTS: A score >= 16 on the Center for Epidemiologic
      Studies Depression Scale defined presence of depressive symptoms. Mean hearing
      level for each ear was defined as the pure-tone average of the following
      thresholds: 0.5, 1.0, 2.0 and 4.0 kHz; the value for the better hearing ear was
      retained for analysis. Hearing loss was defined as inability to hear at
      thresholds >= 25 dB in both ears. A subjective measure of perceived hearing loss
      was also used. Serum triglyceride, total-, LDL- and HDL-cholesterol
      concentrations were assessed in fasting blood samples and established cutoffs
      were used in multivariable logistic regression models. The interaction between
      hearing/hearing loss (independent variables) and each of the four lipid
      parameters was tested. RESULTS: Even though the interaction tests regarding LDL-,
      HDL- cholesterol, and triglyceride status were statistically significant, the
      subgroup analyses revealed few significant and somewhat unexpected findings. In
      fact, among individuals with low LDL-cholesterol, unlike their counterparts with
      high LDL-cholesterol, there was an inverse association between hearing level in
      the better hearing ear and depressive symptoms (OR= 0.94; 95% CI: 0.89-0.99).
      Regarding the subjective measure of hearing, a few of the dyslipidemia-moderated
      associations were statistically significant, albeit not all in the predicted
      direction. CONCLUSIONS: The findings provide some support for moderation of the
      association between hearing/hearing loss and depressive symptoms by dyslipidemia,
      with important lipid-specific and hearing measure-specific differences. The
      results could serve as impetus for future investigations in order to identify and
      target population subgroups with increased vulnerability to depression in the
      context of both sensory disability and aging.

PMID- 29188894
TI  - Vitamin D and the Mechanisms, Circumstances and Consequences of Falls in Older
      Adults: A Case-Control Study.
AB  - OBJECTIVES: To determine i) whether cases of elderly fallers had lower serum 25
      hydroxyvitamin D (25OHD) concentration than controls without history of falls;
      and ii) whether serum 25OHD concentration was associated with specific
      mechanisms, circumstances and consequences of falls. DESIGN: Case-control study
      with a 1:2 ratio. SETTING: Geriatric ward of the University Hospital of Angers,
      France, between February 2012 and March 2014. PARTICIPANTS: 216 inpatients (72
      cases and 144 age- and gender-matched controls). MEASUREMENT: Falls were defined
      as involuntary events causing the person to the ground or other lower level. The
      main mechanisms, circumstances and consequences of falls were identified using
      standardized questionnaires. Vitamin D deficiency was defined as serum 25OHD
      concentration <=25nmol/L. Age, gender, body mass index, polypharmacy, use
      antihypertensive drugs, use psychoactive drugs, disability, cognitive
      performance, serum concentrations of parathyroid hormone, creatinine and albumin,
      and season of evaluation were used as potential confounders. RESULTS: 216
      participants (72 cases and 144 controls) were included in the study. There was no
      between-group difference in the prevalence of vitamin D deficiency (P=0.176).
      After adjusting for confounding factors, vitamin D deficiency was positively
      associated with falls (OR=4.03, P=0.014). Finally, the fallers with vitamin D
      deficiency exhibited more often orthostatic hypotension (68.8% against 33.3%,
      P=0.039) and a history of recurrent falls (85% against 50%, P=0.002) than those
      without vitamin D deficiency. CONCLUSION: This case-control study reported that
      vitamin D deficiency was associated with falls in older inpatients. There was a
      greater prevalence of orthostatic hypotension and of the reccurrence of falls
      among fallers with vitamin D deficiency, suggesting that vitamin D may influence
      the conditions predisposing to falls rather than the fall by itself.

PMID- 29188893
TI  - Therapeutic Role of Punica Granatum (Pomegranate) Seed Oil Extract on Bone
      Turnover and Resorption Induced in Ovariectomized Rats.
AB  - CONTEXT: Postmenopausal osteoporosis is mostly caused by increased bone
      remodeling resulting from estrogen deficiency. Hormone replacement therapy (HRT)
      is used to prevent osteoporosis, but it increases the risk for breast cancer,
      thromboembolism, strokes, and heart attacks. Pomegranate seed oil extract (SOE)
      is rich in phytoestrogen and antioxidant compounds. OBJECTIVES: To evaluate the
      therapeutic role of SOE against bone turnover, resorption and osteoporosis
      induced in ovariectomized rats as a postmenopausal model and comparing the
      results with those from Generic CycloProgynova drug (D). DESIGN: The study used
      western albino rats undergo bilaterally ovariectomization as a model for
      postmenopausal. SETTING: The study took part in a laboratory setting. ANIMALS:
      Forty female western albino rats (age: 3-4 months) weighing 150-180 gm.
      MEASUREMENTS: Rats were divided into four groups, 10 rats each; SC-group: Sham
      control = untreated and unovariectomized rats; OVX-group = ovariectomized rats;
      (OVX-SOE) and (OVX-D) groups = OVX rats were treated with SOE and D,
      respectively. Bone markers (BMs) especially osteocalcin (BGP), alkaline
      phosphatase (ALP), tartarate resistance acid phosphatase (TRAcP), bone weight,
      bone calcium concentration, serum electrolytes (calcium, sodium and potassium)
      and serum estradiol (E2) level and histopathological examination of bones were
      determined. Also lipid profile, uric acid, prothrombin time (INR) and liver and
      kidney functions were measured to evaluate the adverse effects of SOE and D.
      RESULTS: In OVX group the activities of ALP and TRAcP and the levels of BGP,
      serum calcium, sodium and body weight were significantly higher (p<=0.05) than SC
      group, while bone calcium concentration, bone mass, serum E2 and potassium level
      as well as uterus mass were significantly lower (p<=0.05). Also histopathological
      results revealed that the outer cortical bone became thinner, while the
      cancellous bone trabeculae lost their normal architecture. Moreover in OVX group
      lipid profile and uric acid levels were significantly higher (p<=0.05) than SC
      group, but there were no significant changes (p<=0.05) in INR level, liver and
      kidney functions. Treatment of OVX rats with SOE or D for 12 weeks improved both
      the architecture of bones as shown from the histopathological results and BMs,
      serum electrolytes and E2 levels (p<=0.05) which approached SC-group. Moreover
      after treatment of OVX rats with SOE the levels of lipid profile and uric acid
      were improved and approached SC-group, while liver function became significant
      lower (p<=0.05) than SC-group. Also there were no significant changes (p<=0.05)
      in kidney functions and INR of (OVX-SOE), OVX and SC groups. In contrast in (OVX
      D) group the levels of lipid profile, liver and kidney functions, uric acid and
      INR were significantly higher (p<=0.05) than those of OVX and SC groups.
      CONCLUSION: The results of this study show that SOE has therapeutic effects on
      osteoporosis, while it has no adverse effects on lipid profile, uric acid, liver
      and kidney functions when compared to HRT. SOE offers a promising alternative in
      the design of new strategies in nutritional management of age-related bone
      complications.

PMID- 29188895
TI  - Supplementation of Mussel Peptides Reduces aging Phenotype, Lipid Deposition and
      Oxidative Stress in D-Galactose-Induce Aging Mice.
AB  - OBJECTIVES: Aging is associated with glucose and lipid metabolism disorder. We
      aimed to examine the effects of mussel peptides on protecting against aging by
      regulating glucose and lipid metabolism. METHODS: For the aging model, d
      galactose (200 mg/kg) was administered subcutaneously to 8-month-old mice for 8
      weeks. Mussel peptides (1,000 mg/kg) were simultaneously administered by
      intragastric gavage. The glucose and lipid metabolism profiles, aging phenotype
      and peroxisome proliferator-activated receptors (PPARs) expression in the liver
      and adipose tissue of ICR mice were measured. RESULTS: D-galactose-treated mice
      showed pronounced fat deposition and impaired glucose and lipid homeostasis,
      along with increased oxidative damage and aging. Mussel peptides improved
      metabolic status by reducing serum glucose and triglyceride levels, insulin
      resistance and hepatic free fatty acid, as well as enhancing serum high-density
      lipoprotein (HDL) level and hepatic glycogen content, accompanied with
      amelioration of aging phenotype and fat deposition. Moreover, mussel peptides
      ameliorated oxidative stress in aged liver tissues and promoted expression of
      peroxisome proliferator activated receptors alpha (PPARalpha) and gamma
      (PPARgamma) in liver and adipose tissues. CONCLUSIONS: These results indicate
      that mussel peptides protect against lipid metabolic disorders associated with
      aging via maintaining oxidative stress homeostasis and elevated expression levels
      of PPARs.

PMID- 29188896
TI  - Vitamin B12 and Homocysteine Associations with Gait Speed in Older Adults: The
      Baltimore Longitudinal Study of Aging.
AB  - OBJECTIVES: This study aimed to assess the independent associations of serum
      levels of vitamin B12 and plasma concentrations of homocysteine with gait speed
      decline. DESIGN, SETTING, PARTICIPANTS: This study utilized longitudinal analysis
      of participants 50 years or older from The Baltimore Longitudinal Study of Aging,
      N=774. MEASUREMENTS: Gait speed (m/s) was assessed using the 6-meter usual pace
      test. Vitamin B12 and homocysteine concentrations were collected using standard
      clinical protocols. Linear mixed effects regression was stratified by baseline
      age category (50-69, 70-79, and >=80 years old). RESULTS: Mean follow-up time for
      the total study sample was 5.4 +/- 2.0 years. No association between vitamin B12
      and gait speed decline over the follow-up time for any age group was found.
      Elevated homocysteine concentrations were associated with decline in gait speed
      after adjustment for covariates (50-69: beta= -0.005, p=.057; 70-79: beta= 
      0.013, p<.001, >=80: beta= -0.007, p=.054). CONCLUSION: Homocysteine and vitamin
      B12 are inversely related, yet only homocysteine was associated with gait speed
      decline in this population of healthy older adults. Given these results, future
      research should be directed towards investigating the relationship in populations
      with greater variation in vitamin B12 concentrations and other mechanisms
      influencing homocysteine concentrations.

PMID- 29188897
TI  - Better Body Composition and Lipid Profile Can Be Associated with Vitamin D Status
      in Spanish Elderly? The PHYSMED Study.
AB  - Studies have shown that vitamin D deficiency increases the risk for lipid
      metabolism disorders, but this relationship has provided inconsistent results in
      elderly. Thus the aim was to assess the association between body composition and
      blood lipid profile levels on serum 25-hydrovitamin D [25(OH)D] concentration in
      Spanish elderly. A cross-sectional multicentre study was carried out in 383
      participants (58.2% females) aged of 55-88 years. Fasting blood samples analyzed
      serum concentrations of 25(OH)D, low-density lipoprotein (LDL), high-density
      lipoprotein (HDL), triglycerides (TG) and total cholesterol (TC). Body
      composition parameters (fat mass, fat free mass) were obtained by bioimpedance,
      waist circumference (WC), physical activity and vitamin D intake were also
      evaluated. BMI, fat mass and total fat mass were lower in vitamin D sufficient
      subjects than vitamin D insufficient and deficient subjects, but this difference
      was not significant (p>0,05). Those with vitamin D adequate levels also showed
      lower TC/HDL ratio than those who had inadequate (insufficient or deficient)
      vitamin D levels (p=0.04). Significant association between 25(OH)D and BMI, waist
      circumference, total muscle mass, TC/HDL-c ratio, HDL and TG (for all p<= 0.05)
      was found after controlling for some confounders. Subjects with inadequate HDL
      levels (<40mg/dL) showed 1.7 times higher odds than vitamin D deficiency than
      those with adequate HDL levels (>60mg/dL) (95% CI= 1.10 to 2.85 p= 0.017) and WC
      was negatively associated with vitamin D status odds ratio of 0.98 (0.96 to 1.00;
      p= 0.04). Vitamin D concentration was positively correlated with HDL-c and total
      muscle mass, as well as negatively correlated with WC, LDL-c/HDL-c and TC/HDL-c
      independently of age, gender and some confounders.

PMID- 29188898
TI  - Influence of High-Fat Diet on Bone Tissue: An Experimental Study in Growing Rats.
AB  - BACKGROUND: The relationship between obesity and bone tissue remains
      contradictory, especially when the effect of high-fat diet is assessed in
      experimental models. The aim of this study was to evaluate the effects of high
      fat diet on bone metabolism of growing rats. METHODS: Twenty weaned female Wistar
      rats were equally divided into two groups: SD (standard diet) and HFD (high-fat
      diet with 60 % of energy as fat). After five weeks of the two diets, the rats
      were euthanized, and the liver, blood and bones extracted. The liver was analysed
      for malondialdehyde (MDA) and reduced glutathione (GSH) concentrations. Blood was
      analysed by the ELISA method for osteoprotegerin (OPG) and tumour necrosis factor
      ligand superfamily member 11 (TNFSF11/RANKL). The bone tissue was analysed by
      dual-energy X-ray absorptiometry (DXA), mechanical tests, computed
      microtomography, histological quantitative analysis and scanning electron
      microscopy. The gene expressions of PPAR-gamma Runx-2, RANKL and Cathepsin-K were
      also evaluated. RESULTS: HFD caused an increase in the MDA concentration,
      indicating oxidative stress. It also increased the expression of PPAR-gamma,
      which is the gene that is related to adipocyte differentiation. There was an
      increase in BMD of the tibia of animals fed with the HFD, but other
      microstructural and mechanical properties were maintained unaltered. In addition,
      there were no changes in the gene expressions related to the differentiation of
      osteoblasts and osteoclasts, as well as no changes to the biochemical markers of
      bone formation and bone resorption. CONCLUSION: Liver and gene parameters are
      changed in response to the HFD. However, although there was an increase in BMD,
      the microstructure and function of the bone did not change after a 5-week HFD.

PMID- 29188899
TI  - Utility of Three Prognostic Risk Scores in Predicting Outcomes in Elderly Non
      Malignant Patients after Percutaneous Gastrostomy.
AB  - BACKGROUND/OBJECTIVES: Percutaneous endoscopic gastrostomy is a method of
      providing enteral feeding to patients who cannot take adequate oral nutrition.
      The aims of this study were to determine the performance of malnutrition and
      mortality scoring systems for predicting short and long-term mortality in elderly
      patients who had undergone gastrostomy procedure due to non-malignant conditions.
      DESIGN: Retrospective cohort study. SETTING: University hospital in Turkey.
      PARTICIPANTS: 155 individuals aged 65 and older principally hospitalized for non
      malignant diseases and require percutaneous endoscopic gastrostomy. MEASUREMENTS:
      "Geriatric Nutritional Risk Index", "Malnutrition Universal Screening Tool"
      (MUST) and "Portsmouth-Physiological and Operative Severity Score for the
      enUmeration of Mortality and Morbidity" (P-POSSUM) scores were calculated. The
      ability of these scores to predict mortality was determined. RESULTS: The mean
      survival period was 9.59+/-6.0 months and mortality rate was 80.6%. The
      performance of "Geriatric Nutritional Risk Index" was superior to MUST and P
      POSSUM in predicting long-term survival of gastrostomy patients; 94.1% of
      patients were alive with a cut-off value of 90 for "Geriatric Nutritional Risk
      Index" (sensitivity: 92% CI 85.9-95.6 and specificity: 90% CI 74.3-96.5).
      Survival analysis showed that patients (n=7) with a "Geriatric Nutritional Risk
      Index" score of > 98 before the gastrostomy had the longest survival time, while
      patients (n=102) with a "Geriatric Nutritional Risk Index" score of < 82 had the
      worst outcome. CONCLUSIONS: A scoring system such as "Geriatric Nutritional Risk
      Index" should be considered as a risk scoring system for predicting early and
      late mortality at gastrostomy and also assist in making decisions such as timing
      of gastrostomy procedure.

PMID- 29188900
TI  - Effects of Aerobic and Resistance Training Combined with Fortified Milk on Muscle
      Mass, Muscle Strength, and Physical Performance in Older Adults: A Randomized
      Controlled Trial.
AB  - OBJECTIVES: Fortified milk and resistance training (RT) increase muscle mass,
      muscle strength, and physical performance in older adults, but it remains unclear
      whether RT combined with aerobic training (AT) would have stronger effects on
      these outcomes. The purpose of this study was to examine the effects of aerobic
      and resistance training (ART) combined with fortified milk consumption on muscle
      mass, muscle strength, and physical performance in older adults. DESIGN: Open
      labeled randomized controlled trial. SETTING: University of Tsukuba.
      PARTICIPANTS: Fifty-six older adults aged 65-79. INTERVENTION: Participants were
      randomly allocated into resistance training (RT + fortified milk, n = 28) and
      aerobic and resistance training (ART + fortified milk, n = 28) groups. All
      participants attended supervised exercise programs twice a week at University of
      Tsukuba and ingested fortified milk every day for 12 weeks. Skeletal muscle index
      ([SMI]: appendicular lean mass/height2) was assessed using dual-energy X-ray
      absorptiometry as a muscle mass measure. One-repetition maximum strength was
      measured using four kinds of resistance training machines (chest press, leg
      extension, leg curl, and leg press) as muscle strength measures. Sit-to-stand and
      arm curl tests were also assessed as physical performance measures. MEASUREMENTS:
      The primary measurements were muscle mass and strength. The secondary outcomes
      were physical performance, blood samples, habitual diet, habitual physical
      activity, and medication use. RESULTS: Although the muscle strength and physical
      performance measures significantly improved in both groups, SMI significantly
      improved in only the RT group. There was no significant difference in the change
      in SMI and muscle strength measures between the two groups. However, the change
      in sit-to-stand and arm curl measures in the ART group were significantly higher
      than those in the RT group. CONCLUSIONS: These results suggest that AT before RT
      combined with fortified milk consumption has similar effects on skeletal muscle
      mass and strength compared with RT alone, but it may be a more useful strategy to
      improve physical performance in older adults. Although the mechanism of our
      intervention is uncertain, our program would be an effective prevention for
      sarcopenia in older adults.

PMID- 29188901
TI  - Food Insecurity among Veterans: Findings from the Health and Retirement Study.
AB  - OBJECTIVES: We examined the prevalence of food insecurity in an older population,
      specifically assessing factors associated with food insecurity among U.S.
      military Veterans. METHODS: Data from the 2012 wave of the Health and Retirement
      Study and the 2013 Health Care and Nutrition Mail Survey of 2560 male
      participants (1254 Veterans) were used to estimate the prevalence of food
      insecurity and to identify significant predictors of food insecurity among male
      Veterans. RESULTS: Among male Veterans, 6.4% reported food insecurity, compared
      to 11.9% of male non-veterans (p < 0.01). Younger age, difficulty with daily
      activities and depression were significantly associated with increased odds of
      food insecurity among male Veterans aged 50 to 64. In male Veterans age 65 years
      and older, current smoking, a psychiatric diagnosis and depression were
      significantly associated with increased odds of food insecurity. CONCLUSIONS:
      This study identified significant factors that may be used to target
      interventions to improve nutritional status among older male Veterans.

PMID- 29188902
TI  - Inadequate Glycaemic Control and Therapeutic Management of Adults over 65 Years
      Old with Type 2 Diabetes Mellitus in Spain.
AB  - OBJECTIVES: The glycaemic goals for older patients with type 2 diabetes mellitus
      (DM) are recommended to avoid an HbA1c levels <7%. The purpose of this study was
      to analyse the glycaemic control and therapeutic management of older adults (>=65
      years) with type 2 DM. DESIGN: Pooled analysis of patients enrolled in three
      Spanish cross-sectional epidemiological studies. SETTING: The study was conducted
      between 2009 and 2011 by primary care or specialist physicians. PARTICIPANTS: A
      total of 7,269 patients aged >=65 years with type 2 DM. MEASUREMENTS:
      Sociodemographic, medical history, lifestyle habits, biochemical laboratory
      parameters, comorbidities, type 2 DM complications, and pharmacological treatment
      data collected from medical records. RESULTS: In total, data from 7,269 patients
      were analysed (mean age 73.4 years old; 48.4% male). A total of 10.9% of patients
      had HbA1c levels >=8.5% and 43.2% <7%. The most common comorbidities were
      hypertension (82.0%) and dyslipidaemia (76.6%). The microvascular complications
      were mainly diabetic nephropathy (23.6%) and retinopathy (19.3%). Oral
      antidiabetic drugs (OADs) were taken by 70.5% of patients (sulphonylureas 65.3%),
      4.1% were taking insulin alone and 25.4% took both insulin and an OAD. Half of
      the patients (51.0%) were taking a combination of OADs. CONCLUSION: In
      conclusion, more than half of older patients with type 2 DM had unsatisfactory
      management: approximately one in ten had inadequate glycaemic control (HbA1c
      >=8.5%) despite hypoglycaemic drugs and four in ten were potentially overtreated
      (HbA1c <7%).

PMID- 29188904
TI  - Utilizing the DSM-5 Anxious Distress Specifier to Develop Treatment Strategies
      for Patients With Major Depressive Disorder.

PMID- 29188903
TI  - Medication review by a clinical pharmacist at the transfer point from ICU to
      ward: a randomized controlled trial.
AB  - WHAT IS KNOWN AND OBJECTIVE: Drug-related problems (DRPs) occur frequently in
      hospitalized patients. Patient discharge from the intensive care unit (ICU) to a
      non-ICU ward is one of the most challenging and high-risk transitions of care due
      to the number of medications, and the complexity and acuity of the medical
      conditions that characterize this patient group. Pharmacists could play an
      important role in preventing DRPs. This study was undertaken to evaluate the
      impact on the number and severity of drug-related problems by assigning a
      clinical pharmacist to the transfer process from ICU to wards. METHODS: The study
      was a randomized controlled multicentre trial conducted at the Hospital Network
      of Antwerp between December 2010 and January 2012. The clinical pharmacist
      performed a medical review in both the intervention and control group.
      Recommendations for drug therapy changes were immediately communicated in the
      intervention group but were kept blinded in the control group. The primary
      outcome was expressed as the number of implemented recommendations for drug
      therapy changes. Differences between groups were calculated using mixed effects
      binary logistic regression. RESULTS: Drug-related problems were found in the
      medical records of 360 of the 600 participants (60%). A total of 743
      recommendations could be made, 375 in the intervention group and 368 in the
      control group. 54.1% of these problems were adjusted on time in the intervention
      group vs. 12.8% in the control group. Of 743 recommendations, 24.8% were judged
      by the expert group as major, 13.1% as moderate, 53.4% as minor and 8.9% as
      having no clinical impact. The odds of implementing recommendations of drug
      therapy changes in the intervention group were 10 times the odds of implementing
      recommendations of drug therapy changes in the control group (odds ratio = 10.1;
      95%CI [6.3-16.1]; P < 0.001), even after accounting for differences in types of
      DRP between the groups (odds ratio = 15.6; 95%CI [9.4-25.9]; P < 0.001). WHAT IS
      NEW AND CONCLUSION: The integration of a clinical pharmacist at the transfer
      point from ICU to ward led to a significant reduction in DRPs.

PMID- 29188905
TI  - Review and Meta-Analysis of Epidemiologic Studies of Adult Bipolar Disorder.
AB  - OBJECTIVE: To test whether rates of bipolar disorder (BD) have changed over time
      or vary across geographic regions after adjusting for design features meta
      analyzing epidemiologic studies reporting BD prevalence in adults worldwide. DATA
      SOURCES: Searches in PubMed and PsycINFO using the terms (epidemiology OR
      community OR prevalence) AND (mania OR "bipolar disorder" OR cyclothymi*) AND
      adult and backward searches from published reviews were conducted. STUDY
      SELECTION: Eighty-five epidemiologic studies published in English from 1980
      onward that reported prevalence rates for BD or mania for subjects >= 18 years
      old were included. DATA EXTRACTION: We coded BD prevalence, method of data
      collection, diagnostic criteria, year of study, country, and quality of study
      design and data reporting. Meta-regression tested whether sample characteristics
      influenced prevalence rates using the metafor package in R. RESULTS: Eighty-five
      effect sizes, from 44 countries, from studies spanning the years 1980-2012,
      included 67,373 people with BD. Lifetime prevalence for BD spectrum was 1.02%
      (95% CI, 0.81%-1.29%). Prevalence was moderated by the inclusion of BD not
      otherwise specified (P = .009) and by geographic region; rates from Africa and
      Asia were less than half of those from North and South America. Rates did not
      change significantly over 3 decades after controlling for design features.
      CONCLUSIONS: The overall prevalence rate is consistent with historical estimates,
      but rates vary significantly across studies. Differences in methodology
      contribute to the perception that rates of BD have increased over time. Rates
      varied markedly by geographic region, even after controlling for all other
      predictors. Research using consistent definitions and methods may expose specific
      factors that confer risk for BD.

PMID- 29188906
TI  - Is Psychiatric Epidemiology Still Counting?

PMID- 29188907
TI  - Prescribing Patterns in a Psychiatrically Referred Sample of Youth With Autism
      Spectrum Disorder.
AB  - OBJECTIVE: The aim of this study was to examine the pattern of
      psychopharmacologic interventions in a psychiatrically referred sample of youth
      with autism spectrum disorder (ASD). METHODS: This retrospective chart review
      aimed at collecting demographic and clinical information, including data on DSM
      IV-TR criteria-based psychiatric disorders and related current medication
      treatment and response. Data were collected in December 2011. Clinicians
      identified the target disorder for each medication and any adverse events. Level
      of psychopathology and therapeutic response was assessed by the clinician-rated
      Clinical Global Impressions scale (CGI). RESULTS: Psychiatrically referred youth
      with ASD (n = 54) suffered from multiple psychopathologies (mean = 2.3) and had a
      marked level of morbidity (range of baseline CGI-Severity of Illness mean scores,
      4.3-5.6). The most prevalent psychopathology was ADHD (83%), anxiety disorders
      (67%), bipolar spectrum disorder (43%), and mood disorder not otherwise specified
      (44%). The majority (80%) of the subjects received combination therapy (mean +/-
      SD number of psychotropic medications = 3 +/- 1.5). Forty percent of the
      participants responded on all treatment target symptoms (CGI-Improvement scale
      score <= 2), and an additional 10% experienced response versus nonresponse on a
      relatively greater number of target symptoms. Half of the subjects reported an
      adverse event, most commonly weight gain (28%) and sedation (12%), both from
      antipsychotic medication use. CONCLUSIONS: Psychiatrically referred youth with
      ASD suffer from multiple highly impairing psychiatric disorders that require
      combination pharmacotherapy. These findings highlight the need for further
      research to guide clinical decision-making and treatment.

PMID- 29188908
TI  - Anticholinergic Burden and Cognition in Older Patients With Schizophrenia.
AB  - OBJECTIVE: Older individuals with schizophrenia are at risk of being treated with
      anticholinergic medications due to the prevalence of medical comorbidities and
      polypharmacy. High anticholinergic burden impairs cognition and is a risk factor
      for Alzheimer's dementia. Thus, we assessed the impact of anticholinergic burden
      on Alzheimer's dementia-related and schizophrenia-related cognitive functions in
      older patients with schizophrenia. METHODS: Anticholinergic burden was measured
      using the Anticholinergic Cognitive Burden scale (ACB) in 60 community-dwelling
      patients aged >= 50 years who met DSM-IV criteria for schizophrenia between May
      2007 and November 2011. Cognitive domains affected early in the course of
      Alzheimer's dementia were assessed using the Cambridge Neuropsychological Test
      Automated Battery (CANTAB) Alzheimer's Dementia Battery and the Repeatable
      Battery for the Assessment of Neuropsychological Status. Two CANTAB tests of
      executive function were used to assess deficits common in schizophrenia.
      Regression analyses were used to assess the relationships between anticholinergic
      burden and cognition. A receiver operating characteristic curve was constructed
      to determine an ACB cutoff score to identify those at risk of cognitive
      impairment. RESULTS: ACB scores were associated with spatial working (P = .04)
      and immediate (P = .004) memory and visuospatial ability (P = .02) and showed a
      trend toward association with impaired learning (P = .06), but were not
      associated with attention, executive function, language, or reaction time. An ACB
      cutoff score of <= 1.5 can detect cognitive impairment with a sensitivity of
      90.3% and specificity of 48.3%. CONCLUSIONS: High anticholinergic burden
      contributes to specific cognitive deficits in older individuals with
      schizophrenia that resemble those commonly observed early in the course of
      Alzheimer's dementia. The ACB is a potentially useful screening tool that can
      help identify patients at risk of developing anticholinergic-related cognitive
      impairment.

PMID- 29188909
TI  - [Hospital emergency services in Spain: Differences by autonomous community or by
      system of organization?]

PMID- 29188910
TI  - [On medication errors in hospital emergency departments: steps toward improving
      patient safety].

PMID- 29188911
TI  - [Physical structure, human resources, and health care quality indicators in
      public hospital emergency departments in the autonomous communities of Madrid and
      Catalonia: a comparative study].
AB  - OBJECTIVES: To compare the general, structural, and organizational
      characteristics of public hospital emergency departments in the Spanish
      autonomous communities of Madrid and Catalonia. MATERIAL AND METHODS: Descriptive
      survey-based study covering 3 areas of inquiry: general hospital features (18
      questions), structural features of the emergency department (14 questions), and
      organizational and work-related policies of the emergency department (30
      questions). Hospitals were grouped according to complexity: local hospitals
      (level 1), high-technology or referral hospitals (levels 2-3). RESULTS: We
      studied 26 hospital departments in Madrid (21, levels 2-3; 5, level 1) and 55 in
      Catalonia (24, levels 2-3; 31, level 1). Hospitals in Madrid are in newer
      buildings (P=.002), have more beds on conventional wards and in critical care
      units (P<.001, both comparisons), are more often affiliated with a university
      (P<.001), and serve larger populations (P=.027). The emergency departments in
      Madrid have larger surface areas available for clinical care and more cubicles
      for preliminary evaluations and observation beds (P=.001, all comparisons).
      Hospitals in Madrid also attended a larger median number of emergencies (P<.001).
      More physicians were employed in Catalonia overall, but the numbers of physician-
      and nurse-hours per hospital were higher in Madrid, where it was more usual for
      physicians to work exclusively in the emergency department (92.5% in Madrid vs
      56.8% in Catalonia, P<.001). However, fewer of the employed physicians had
      permanent contracts in Madrid (30.5% vs 75.1% in Catalonia, P<.001). The ratio of
      resident physicians to staff physicians differs between the 2 communities on
      afternoon/evening, night, and holiday shifts (3:1 in Madrid; 1:1 in Catalonia).
      CONCLUSION: The physical and functional structures of hospital emergency
      departments in the communities of Madrid and Catalonia differ significantly. The
      differences cannot be attributed exclusively to geographic location.

PMID- 29188912
TI  - [Medication reconciliation errors according to patient risk and type of physician
      prescriber identified by prescribing tool used].
AB  - OBJECTIVES: To study the frequency of medication reconciliation errors (MREs) in
      hospitalized patients and explore the profiles of patients at greater risk. To
      compare the rates of errors in prescriptions written by emergency physicians and
      ward physicians, who each used a different prescribing tool. MATERIAL AND
      METHODS: Prospective cross-sectional study of a convenience sample of patients
      admitted to medical, geriatric, and oncology wards over a period of 6 months. A
      pharmacist undertook the medication reconciliation report, and data were analyzed
      for possible associations with risk factors or prescriber type (emergency vs ward
      physician). RESULTS: A total of 148 patients were studied. Emergency physicians
      had prescribed for 68 (45.9%) and ward physicians for 80 (54.1%). A total of 303
      MREs were detected; 113 (76.4%) patients had at least 1 error. No statistically
      significant differences were found between prescriber types. Factors that
      conferred risk for a medication error were use polypharmacy (odds ratio [OR],
      3.4; 95% CI, 1.2-9.0; P=.016) and multiple chronic conditions in patients under
      the age of 80 years (OR, 3.9; 95% CI, 1.1-14.7; P=.039). CONCLUSION: The
      incidence of MREs is high regardless of whether the prescriber is an emergency or
      ward physician. The patients who are most at risk are those taking several
      medications and those under the age of 80 years who have multiple chronic
      conditions.

PMID- 29188913
TI  - [A new artificial intelligence tool for assessing symptoms in patients seeking
      emergency department care: the Mediktor application].
AB  - OBJECTIVES: To analyze agreement between diagnoses issued by the Mediktor
      application and those of an attending physician, and to evaluate the usefulness
      of this application in patients who seek emergency care. MATERIAL AND METHODS:
      Prospective observational study in a tertiary care university hospital emergency
      department. Patients with medical problems and surgical conditions (surgery and
      injuries) who did not require immediate emergency care responded to the Mediktor
      questions on a portable computer tablet. The software analyzed the answers and
      provided a list of 10 possible preliminary diagnoses in order of likelihood. The
      patient and the attending physician were blinded to the list to so that the usual
      care process would not be altered. The level of agreement between the physician's
      diagnosis and the Mediktor diagnosis was analyzed. RESULTS: A total of 1015
      patients were included; 622 cases were considered valid for study. Cases were
      excluded if the patients did not meet the inclusion criteria, they did not have a
      discharge diagnosis, they had a final diagnosis expressed as a symptom or their
      final diagnosis was not included in the Mediktor database. The physician's
      diagnosis (the gold standard) coincided with one of the 10 MEDIKTOR diagnoses in
      91.3% of the cases, with one of the first 3 diagnoses in 75.4%, and with the
      first diagnosis in 42.9%. Sensitivity was over 92% and specificity over 91% in
      the majority of common diagnostic groups; the kappa statistic ranged from 0.24 to
      0.98. CONCLUSION: The Mediktor application is a reliable diagnostic aid for the
      most prevalent problems treated in a hospital emergency department. The general
      public finds it easy to use.

PMID- 29188914
TI  - [Vernakalant in hospital emergency practice: safety and effectiveness].
AB  - OBJECTIVES: To study the effectiveness and safety of vernakalant for restoration
      of sinus rhythm in patients with atrial fibrillation (AF) in routine hospital
      emergency department care, and to evaluate factors associated with a more
      effective response. MATERIAL AND METHODS: Prospective multicenter cohort study
      enrolling consecutive patients who were administered vernakalant for medical
      cardioversion of AF between September 2014 through March 2016 in 5 hospitals in
      the Spanish autonomous community of Valencia. RESULTS: We studied 165 cases. The
      median (interquartile range) was 68 years (56-77) years. Cardioversion with
      vernakalant was effective in 77.6% (95% CI, 71.1%-84%). The median time to
      conversion was 8 ( 6-12) minutes after a first dose and 34 (22-62) minutes after
      a second dose. A prior history of cardiac insufficiency was nonsignificantly less
      common in patients who converted with vernakalant (6.3%) than in those who did
      not (18.9%) (adjusted odds ratio [OR], 0.45 [95% CI, 0.13-1.56]; P=.208). Having
      no prior history of AF was nonsignificantly related to greater effectiveness (in
      54.7% vs in 35.1% with prior AF). Duration less than 12 hours was significantly
      associated with greater effectiveness (83.6% vs 59.5%; adjusted OR, 2.76 [95% CI,
      1.12-6.80]; P=.028). Adverse events were reported for 30 patients. None of the
      events had clinically important consequences, and in only 2 cases (1.2%) was it
      necessary to suspend treatment. CONCLUSION: Vernakalant is effective and safe for
      restoring sinus rhythm in the hospital emergency department.

PMID- 29188915
TI  - [Occupational aspects of emergency medicine practice in Catalonia: the OPENCAT
      opinion survey].
AB  - OBJECTIVES: To gather information on the contracting and training of members of
      the Catalan Society of Emergency Medicine (SoCMUE) who work in emergency medicine
      and services in Catalonia. To survey their opinions on certain aspects of
      resource availability and working conditions. MATERIAL AND METHODS: Cross
      sectional descriptive study based on a survey sent to SoCMUE members. We studied
      the opinions of 5 types of respondent: hospital physicians, out-of-hospital
      physicians, hospital nurses, out-of-hospital nurses, and emergency medical
      technicians. Responses were grouped to compare the opinions of physicians and
      nurses and workers in hospital and prehospital settings. RESULTS: We received 616
      responses from 1273 members (48.4% response rate). More physicians than nurses
      come from outside Catalonia and have contracts specifically linked to emergency
      care; in addition, physicians have done less postgraduate training in emergency
      medicine. More hospital staff than prehospital staff have permanent contracts
      linked to the department where they work. More hospital physicians are
      specialized in internal medicine than in family and community medicine. The
      opinion that emergency services are inadequately staffed was widespread. Most
      respondents believed that patient transport is good or adequate. However,
      respondents working in prehospital services expressed a lower opinion of
      transport. Great difficulty in combining work with family (life achieving work
      life balance) was expressed by 13.5% overall, and more often by hospital staff.
      Some type of aggression was experienced by 88.2%; 60% reported the event to
      superiors. Nurses reported aggression more often than physicians. A police report
      was filed by 10.1%. CONCLUSION: Emergency medicine working conditions can be
      improved in Catalonia according to members of SoCMUE. Relations between groups of
      professionals are not optimum in some aspects.

PMID- 29188916
TI  - [Medication errors in a hospital emergency department: study of the current
      situation and critical points for improving patient safety].
AB  - OBJECTIVES: To determine the frequency of medication errors and incident types in
      a tertiary-care hospital emergency department. To quantify and classify
      medication errors and identify critical points where measures should be
      implemented to improve patient safety. MATERIAL AND METHODS: Prospective direct
      observation study to detect errors made in June and July 2016. RESULTS: The
      overall error rate was 23.7%. The most common errors were made while medications
      were administered (10.9%). We detected 1532 incidents: 53.6% on workdays
      (P=.001), 43.1% during the afternoon/evening shift (P=.004), and 43.1% in
      observation areas (P=.004). CONCLUSION: The medication error rate was
      significant. Most errors and incidents occurred during the afternoon/evening
      shift and in the observation area. Most errors were related to administration of
      medications.

PMID- 29188917
TI  - [Implementation of the Hartford Consensus and Tactical Combat Casualty Care
      recommendations in emergency services: a review of the literature].
AB  - en: Recent terrorist attacks involving active shooters or improvised explosive
      devices have shown that traditionally sequenced emergency management leads to
      delays in attending victims and suboptimal outcomes. Tactical medicine, a new
      concept in prehospital care, emerged from experience attending the wounded in
      combat zones, where the Tactical Combat Casualty Care (TCCC) recommendations are
      applied. TCCC targets 3 main causes of preventable death in combat: bleeding from
      extremities, tension pneumothorax, and airway obstruction. A change in the
      delivery of emergency care during terrorist attacks is now required if we are to
      improve survival rates. To that end, strategies based on the TCCC and Hartford
      Consensus recommendations have been developed. Both these approaches describe
      procedures for both first responders and medical professionals to apply in areas
      under threat.

PMID- 29188918
TI  - [Transcatheter aortic valve implantation: what the emergency department physician
      should know].

PMID- 29188919
TI  - [Stings from jellyfish and other venomous marine life: impact on beach lifeguard
      services].

PMID- 29188920
TI  - [Pharmacologic monitoring of acute confusional state in Spanish hospital
      emergency departments].

PMID- 29188921
TI  - [Segmental arterial mediolysis].

PMID- 29188922
TI  - [Comments on the SEMICA study (Emergency Medical Response Systems for Patients
      with Acute Heart Failure)].

PMID- 29188923
TI  - [Authors' reply].

PMID- 29188924
TI  - [Gastric foreign body-induced hematemesis in a body packer].

PMID- 29188925
TI  - [Usefulness of bedside ultrasound in body packer syndrome].

PMID- 29188926
TI  - [Morel-Lavallee lesions the importance of early diagnosis].

PMID- 29188927
TI  - Oral hygiene and mouth care for older people in acute hospitals: part 2.
AB  - Acute hospital admission provides an excellent opportunity to address poor oral
      health in older people, a group rarely seen by dental professionals and for who
      oral health activity in hospital is inconsistent and generally suboptimal. This
      two-part article explores oral hygiene and mouth care provision for older adults
      in acute hospitals. The first article presented the findings of a literature
      review exploring oral and dental disease in older adults, the importance of good
      oral health and mouth care, and the current situation. The second article
      explores clinical recommendations. A change in philosophy is needed to embed oral
      care as an essential component of holistic practice. More research is needed to
      determine the best ways to assess and treat oro-dental problems in older people,
      and promote and restore their oral health in hospitals. Great potential exists to
      innovate and develop new ways of providing care to this group.

PMID- 29188928
TI  - Factors that influence older people's engagement with digital health technology.
AB  - Digital health technology (DHT) encompasses a wide range of applications and
      interventions with the potential to address the health needs of an increasingly
      ageing population. Older people's engagement with DHT depends on many factors,
      and this article summarises understanding of the barriers and facilitators to DHT
      uptake and continued use among older people. Older people's confidence in using
      digital technology, their perceptions of personal benefit from DHT, its design,
      and the support they receive from health professionals and carers in using DHT
      all affect their level of engagement. Understanding these barriers and
      facilitators among the older population creates ways to enable greater numbers to
      benefit from DHT. This article provides information for those who work with, or
      design digital health interventions for, older people to help them to influence
      older people's engagement with these rapidly evolving healthcare innovations.

PMID- 29188929
TI  - Reducing avoidable emergency department attendances through bespoke education.
AB  - AIM: To develop an education and partnership programme between the trust and
      nursing home staff in Northern Ireland. METHODS: Twenty care home nurse champions
      participated in a bespoke Responsive Education and Collaborative Health programme
      provided by the trust. The trust's practice development facilitator supported
      care home staff to develop clinical competencies while observing residents'
      emergency department (ED) attendance trends. RESULTS: After introduction of the
      programme, avoidable ED attendances were reduced by 31% ( n =309) compared with
      the previous year, cost per capita was reduced by L314,340, reliance on community
      nursing was reduced, and the health and experience of the care home population
      were improved. CONCLUSION: ED attendances and reliance on community nursing
      reduced, identifying a compelling need for continuing partnership, training and
      facilitation between the trust and independent sector.

PMID- 29188930
TI  - Should hepatocellular cancer by screened in Finland?
AB  - Almost 2 000 people die each year from the adverse effects of alcohol use in
      Finland. Liver cirrhosis is the cause of death in half of the cases. Although the
      annual risk of hepatocellular cancer for a cirrhosis patient is 1 to 4%, more
      than 95% of the deaths result from complications caused by the cirrhosis, not the
      cancer. It seems that nontargeted screening of hepatocellular cancer for those
      affected with alcoholic cirrhosis or nonalcoholic steatohepatitis is not cost
      effective. Screening may, however, be advisable when the risk of cancer is high,
      provided that treatment of a detected cancer is possible.

PMID- 29188931
TI  - Treatment of hypertrophic scars and keloids.
AB  - Differentiation of a hypertrophic scar from a keloid is important with regard to
      the planning of treatment. Keloids arise following any skin injury and may grow
      disproportionately large as compared with the original wound. Treatment of
      keloids is challenging both for the patient and the attending physician.
      Treatment of hypertrophic scars aims to abate the symptoms and accelerate scar
      maturation. The goal in the treatment of keloids is excision of the keloid or
      stopping its growth, lessening of symptoms and avoidance of recurrence.

PMID- 29188932
TI  - The evolving treatment of ANCA-associated vasculitides.
AB  - Prevention of organ damage and maintenance of long-term remission are the
      principal goals for treatment of ANCA-associated vasculitides. This can be
      accomplished by early diagnosis and swift initiation of remission-inducing
      agents. Outcome has improved but relapses and glucocorticoid- and
      cyclophosphamide-related toxicity are still major concerns. For remission
      induction in generalized disease a combination of glucocorticoids and
      cyclophosphamide or rituximab is used. Rituximab is suitable especially for
      younger patients with fertility concerns and when cyclophosphamide avoidance
      otherwise is desirable. In the treatment of relapses and refractory disease,
      rituximab has proved effective. As maintenance treatment rituximab prevents
      relapses more effectively than azathioprine.

PMID- 29188933
TI  - Ascites in newborns - a diagnostic challenge.
AB  - Isolated fetal ascites is a rare finding in prenatal ultrasound examination. The
      finding is always aberrant and requires further exploration. More than half of
      fetal ascites findings are associated with structural anomalies. Other causes
      include prenatal infections and genetic disorders. The cause and time of
      detection of ascites have an influence on the baby's prognosis. In spite of
      careful examinations the cause of ascites frequently remains open during
      pregnancy. During the first hours of life the baby needs intensive care, and when
      necessary, etiologic exploration will be simultaneously continued.

PMID- 29188934
TI  - Treatment of adult acute myeloid leukemia.
AB  - The aim of this study was to analyze the treatment results of 180 adult AML
      patients treated at Turku University Hospital from 2002 to 2012. 124 patients
      received intensive therapy according to the protocol of the Finnish Leukemia
      Group. 86% of them achieved remission. 46 patients underwent allogeneic stem cell
      transplantation which was beneficial for high and intermediate risk disease. 60 -
      70% of patients under 60 years old can be cured. The genetic profile of the
      disease, patient age and treatment response had a significant impact on survival.
      Our treatment results are comparable with data in literature.

PMID- 29188935
TI  - A good start for scientific supervision.
AB  - Clinical research work is mostly supervised besides daily work. Good time
      management skills are in fact an essential prerequisite for success, also
      influenced by various qualities of the supervisor and the supervisee. One pattern
      will not work in all supervisory relationships. Functional communication plays a
      particularly central role. Attention should be paid on the regularity, quality
      and effectiveness of supervisory discussions. On the other hand, group
      supervision has proven to be effective and will also facilitate the continuity of
      supervision. Goals and desires set for the partners can be structured by applying
      supervision contracts.

PMID- 29188936
TI  - Case report: Two severe cases of suicide attempts using nicotine containing e
      cigarette liquid.
AB  - The use of electronic cigarettes and nicotine-containing liquids is getting more
      common, thus increasing the risk for intentional or unintentional nicotine
      poisoning. The results of ingestion of nicotine can be severe, even fatal. We
      describe two different cases of severe poisonings caused by nicotine-containing
      electronic cigarette liquids.

PMID- 29188937
TI  - Prehospital Pain: To eradicate, or not to eradicate? That is the question.

PMID- 29188939
TI  - Clinical Performance: Supervising EMS officer competencies and credentialing.

PMID- 29188938
TI  - Naloxone Conundrum: Reduce risk in managing the opioid overdose patient.

PMID- 29188940
TI  - Etiology, diagnostics and treatment of cardiogenic stroke.
AB  - Approximately 15 to 40% of cerebral infarctions and transient ischemic attacks
      (TIA) are of cardiac origin. Knowledge of a significant cardiac disease arouses
      the suspicion of cardiogenic embolism, but its diagnosis requires identification
      of the source of embolism. Atrial fibrillation is the most common cause of
      cardiogenic embolism, and should be actively sought after an ischemic
      cerebrovascular attact. The detection of atrial fibrillation or an intracardiac
      thrombus in these patients requires initiation of permanent anticoagulant
      therapy. Transesophageal echocardiography (TEE) has proven to be more sensitive
      than transthoracic echocardiography (TTE) in detecting certain possible
      cardiogenic sources of embolism.

PMID- 29188941
TI  - Distal myopathies in Finnish patients.
AB  - Distal myopathies are a group of rare muscular dystrophies comprising more than
      20 different genetic entities. The first distal myopathy in Finland, tibial
      muscular dystrophy, was identified more than 20 years ago. Muscle weakness
      predominantly affects the feet and hands, although variable weakness can be
      detected clinically and on muscle MRI in the proximal muscles in the later stages
      of the disease. Advanced molecular genetic techniques have enabled identification
      of several distinct distal myopathies in Finland. The clinical findings of
      different distal myopathies overlap, but there are also distinguishable
      differences that might help final genetic diagnostics.

PMID- 29188942
TI  - HIV infection and cancer.
AB  - Cancers in HIV-infected patients are divided into the AIDS-defining and non-AIDS
      defining cancers. In the era of effective antiretroviral therapy there has been a
      significant decrease in the incidence of AIDS-defining cancers, whereas the
      number of non-AIDS defining cancers is on the rise. This is partly explained by
      the frequent occurrence of conventional risk factors for cancers, but also HIV
      infection itself seems to further increase the risk. If an HIV-infected person is
      diagnosed early enough, his/her life expectancy corresponds to that of the
      general population. Therefore the treatment goal of cancers in HIV-infected
      patients should be the same as for HIV negative subjects. Antiretroviral agents
      have significant drug-drug interactions with many other medicines. These must
      always be taken into account when planning the treatment of HIV-infected
      patients.

PMID- 29188943
TI  - Could obesity be an infectious disease?
AB  - The accomplishments in combating the obesity epidemic have thus far been
      insufficient. Indeed, the background to the increase in overweight and obesity is
      more complex than is generally anticipated. Recent scientific data suggest that
      the gut microbiota affects two main causes of obesity: energy harvest and storage
      from the diet, thereby increasing energy efficiency, and low-grade inflammatory
      response and impairment of gut barrier function. Consequently, considerable
      research interest is currently focusing on characterizing and manipulating the
      gut microbiota in attempt to reverse the intergenerational progression of obesity
      and its comorbidities. The proof of causality requires clinical interventions in
      well-characterized populations and documentation of the mechanisms.

PMID- 29188944
TI  - Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

PMID- 29188945
TI  - Elevated liver enzymes - what next?
AB  - Owing to laboratory automation, elevated liver enzymes are increasingly found in
      persons who are either asymptomatic or present with vague symptoms. The majority
      of slightly elevated liver enzymes detected in Finland result from excessive
      alcohol use, a drug or non-alcoholic fatty liver disease. On the other hand,
      disregarding pathological liver enzymes may lead to a delay of the treatment of a
      liver disease. In addition to careful anamnesis and status, systematic targeting
      of investigations is often the quickest way to correct diagnosis and assessment
      of need for treatment.

PMID- 29188946
TI  - A jaundiced patient at the emergency department.
AB  - Jaundice is a common cause for seeking medical attention at an emergency
      department. The doctor on call should be able to recognize patients whose
      jaundice requires emergency investigations and treatment in specialized care.
      Most patients can be treated electively on an urgent referral. Ultrasound scan of
      the liver will in most cases clarify whether a liver disease or a biliary tract
      obstruction is in question, and whether the patient should be referred to an
      internist or a surgeon.

PMID- 29188947
TI  - Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

PMID- 29188948
TI  - What to do when I find a focal lesion in the liver?
AB  - A focal lesion in a healthy liver of a person not having cancer is almost always
      benign. Diagnosis is often achieved on the basis of anamnesis and imaging
      findings. A histologic specimen is required in the case of suspected malignant
      tumor or hepatocellular adenoma. Magnetic resonance imaging is the primary
      investigation for an unresolved focal lesion of a cancer patient, and the
      histologic specimen will, when necessary, be taken only after this. Early
      detection of metastases of colorectal cancer in particular is important, since
      metastases that have spread to the liver or lungs may be operable. A focal lesion
      in a cirrhotic liver is either a regenerative nodule or hepatocellular carcinoma.

PMID- 29188949
TI  - Fatty liver - so what?
AB  - Approximately one third of the Finnish adult population are affected with
      overweight-related non-alcoholic fatty liver disease (NAFLD). NAFLD can appear as
      a simple fat accumulation in the liver of the liver, but in some individuals the
      condition may advance to non-alcoholic steatohepatitis (NASH) and even to liver
      cirrhosis. In many cases, NAFLD is detected as an incidental finding. In
      differential diagnosis, the most common alternatives are alcohol use, drugs and
      viral hepatites. For a patient with NAFLD, the risk factors of cardiovascular
      diseases should be investigated and the possibility of having NASH and liver
      fibrosis assessed. Targeted therapy for NASH is not yet available.

PMID- 29188950
TI  - Diagnosis for liver fibrosis - noninvasively.
AB  - Noninvasive tests are utilized in chronic liver diseases to assess excessive
      connective tissue. Blood tests such as the N-terminal peptide of procollagen
      (PIIINP) and APRI (ASAT/platelet count) measure the formation and degradation of
      connective tissue or liver function. Elastography (Fibroscan) is based on the
      propagation of ultrasound in liver tissue, accelerated by fibrosis: the results
      are more sensitive and accurate than those based on blood tests. Reliable
      detection of severe fibrosis and cirrhosis is possible with Fibroscan along with
      determining normal liver tissue.

PMID- 29188951
TI  - Pain Relief: Is this patient in pain or seeking a fentanyl fix.

PMID- 29188952
TI  - Treatment of ascites and its complications.
AB  - The underlying cause of ascites should always be treated if possible. Adhering to
      a low-salt diet is most important in the treatment of ascites. Diuretics are used
      in the treatment of clinically established and abundant ascites. The first-line
      drug in diuretic therapy is spironolactone, when necessary in combination with
      furosemide. The most important complications of ascites are hepatorenal syndrome
      and spontaneous bacterial peritonitis. The development of ascites lowers the
      quality of life, and is associated with significant mortality. Although new
      groundbreaking therapies are not available, prognosis of the patients is expected
      to be improved through optimization of current therapies.

PMID- 29188953
TI  - Standing the Heat: Uncommon chief complaint requires rapid management.

PMID- 29188955
TI  - Hands-On Defibrillation: Is an AED shock safe during compressions?

PMID- 29188954
TI  - Pregnant hepatitis B carrier.
AB  - While screening for viral hepatitides is not carried out among women of
      reproductive age in Finland, maternity clinics offer all pregnant women screening
      for hepatitis B during early pregnancy. A hepatitis B carrier should discuss the
      timing of pregnancy. In general, pregnancy does not influence the course of
      hepatitis B. The most significant route of transmission is still the perinatal
      one, from the mother to the newborn infant. The younger the age when the
      infection is contracted, the higher is the risk of it becoming chronic and
      complicated. The risk of transmission correlates with the mother's serum HBV-DNA
      level and also with HBeAg positivity. At the beginning of the third trimester
      tenofovir decreases the replication of the virus and prevents the newborn infant
      from infection.

PMID- 29188956
TI  - Risk factors for deep infection following plate fixation of proximal tibial
      fractures.

PMID- 29188957
TI  - Duck Vs. Bus: Seattle Fire Department manages complex MCI on Aurora Bridge.

PMID- 29188958
TI  - The Perfect MCI Resources.

PMID- 29188959
TI  - Aetiology of in-hospital cardiac arrest on general wards.

PMID- 29188960
TI  - Overdose Nation: A look at EMS' role in the U.S. opioid epidemic.

PMID- 29188961
TI  - Liraglutide and Renal Outcomes in Type 2 Diabetes.

PMID- 29188963
TI  - Revisiting Naloxone: A different take on overdose guidelines from Lee County,
      Fla.

PMID- 29188962
TI  - Liraglutide and Renal Outcomes in Type 2 Diabetes.

PMID- 29188964
TI  - Incidence of subarachnoid hemorrhage is decreasing together with decreasing
      smoking rates.

PMID- 29188965
TI  - Fentanyl Rising: EMS strategies for combatting the increasing use and abuse of
      highly potent opioids.

PMID- 29188966
TI  - Vitamin K: from coagulation to calcification.
AB  - Vitamin K is not only essential for the synthesis of coagulation factors in the
      liver, but it also strengthens the bones and prevents calcification of the
      arteries. These effects are mediated through the same mechanism, i.e.
      carboxylation of Gla target proteins. The discovery of novel Gla proteins that
      are not associated with blood coagulation or calcium metabolism indicates that
      vitamin K has additional effects in the pancreas and the central nervous system,
      for example. As dietary supplements, vitamin K1 of plant origin and vitamins K2
      of bacterial origin may exert different effects.

PMID- 29188967
TI  - Liraglutide and Renal Outcomes in Type 2 Diabetes.

PMID- 29188968
TI  - Artemisaiae as medicinal and herbal medicinal plants from ancient times to the
      present day.
AB  - The 2015 Nobel Prize in Physiology and Medicine was awarded to Chinese Youyou Tu
      for her work on an antimalarial drug that she isolated from sweet wormwood
      (Artemisia annua L) and absinthe (Artemisia absinthium L) belonging to the genus
      of Artemisia. In this article we deal with the use of Artemisiae as medicinal
      plants through the ages, and several pharmacologically active compounds can be
      obtained from species of the genus Artemisia. We will particularly focus on two
      medicinally interesting species of Artemisiae - sweet wormwood and absinthe - as
      well as two pharmacologically significant compounds found in them, artemisin and
      thujone.

PMID- 29188969
TI  - Etiology of acute pancreatitis.
AB  - Acute pancreatitis (AP) is a common disease. In Finland, the most common
      etiological factors are alcohol abuse and biliary stone disease. Often the
      etiology of AP is multifactorial. AP may also occur as a complication after ERCP,
      pancreatic operation or ultrasound guided biopsy. It is important to find out the
      etiological factors to be able to prevent a recurrence of AP. It is estimated
      that only 5 - 10% of AP-cases should be declared as idiopathic. Anamnesis of
      alcohol consumption, medication, family history, injuries, and disease history
      should reveal many of the risk factors. The initial radiological imaging is
      ultrasound, which can be repeated to increase the sensitivity for detecting
      gallstones as the etiological factor. In certain cases MRCP, computed tomography
      or endoscopic ultrasound are needed.

PMID- 29188970
TI  - The Science of Pain. A guide to prehospital pain management.

PMID- 29188971
TI  - Special K For Special Situations. A review of ketamine for prehospital use.

PMID- 29188972
TI  - Which drugs can be used during pregnancy?
AB  - In many cases the decisions on drug therapy during pregnancy have to be made
      without evidence-based information about the effectiveness and safety of the
      treatment. While few drugs are known with certainty to be harmful for fetal
      development, the evidence for evaluating harm to the fetus is insufficient for
      the majority of drugs. The differentiation of fetal organs takes place during the
      early weeks of pregnancy, whereby it is imperative that the mother's medication
      be revised already when planning a pregnancy. A drug should primarily be chosen,
      for which experience has accumulated about its use during pregnancy and is not
      suspected or known to be associated with adverse effects.

PMID- 29188973
TI  - Antimicrobial peptides - a part of innate immunity.
AB  - Antimicrobial peptides (AMP) are evolutionary ancient molecules produced by
      nearly all living organisms, both prokaryotic and eukaryotic cells. More than
      2000 AMPs have now been identified. These peptides are produced by most human
      cell types, such as those in the skin and mucous membranes and blood. Each tissue
      has a different spectrum of AMPs. Antimicrobial capacity depends on the
      structural characteristics such as charge and amphiphilicity that allow the
      insertion and/or penetration of AMP into the membranes of microorganisms or other
      cells. AMPs may have importance in the pathogenesis of neurodegenerative diseases
      and type 2 diabetes. The most investigated AMPs are defensins and cathelicidin LL
      37.

PMID- 29188974
TI  - Alternative Pathways: London Ambulance Service's innovative response for patients
      presenting with mental health problems.

PMID- 29188975
TI  - Hirayama disease.
AB  - Hirayama is a form of cervical myelopathy affecting mainly young men. The
      cardinal features include progressive, either symmetrical or asymmetrical
      muscular weakness and atrophy of muscles innervated by C7-Th1 motoneurons. The
      application of soft daytime collar during the early stage of illness can halt the
      progression of illness.

PMID- 29188976
TI  - Less Traveled: How ATCEMS chose a new path to fight worker fatigue.

PMID- 29188977
TI  - Optimized recovery programs in gastrointestinal surgery.
AB  - Optimized or enhanced recovery programs have been applied to intestinal surgery
      already for a long time. They are being widely initiated also within bariatric,
      hepatic and pancreatic surgery. The programs aim at an increasingly better well
      being of surgical patients by avoiding procedures which slow down the recovery
      and favoring those that promote it. Informing the patient is also an essential
      part of the programs. Effective pain management avoiding opioids, early started
      oral nutrition, and mobilization immediately after the operation prevent
      postoperative decreased intestinal motility and nausea. At best, the programs
      will guarantee the patients' excellent recovery and shorten the length of stay on
      the ward.

PMID- 29188978
TI  - Hands On: Product Reviews From Street Crews.

PMID- 29188979
TI  - Liraglutide and Renal Outcomes in Type 2 Diabetes.

PMID- 29188981
TI  - Last Word: The Ups and Downs of EMS.

PMID- 29188980
TI  - Myotonia in ion channel diseases of muscle.
AB  - Ion channel dysfunctions of the muscular cell membrane are usually inheritable,
      rare diseases. They may become manifest as relatively mild symptoms of muscle
      stiffness and pain, myotonia or paralysis. We describe two young patients who had
      an inherited ion channel disease of the muscular cell membrane with mild
      symptoms. The first patient had a chloride channel dysfunction of the muscular
      cell membrane, the second one a sodium channel dysfunction. In electromyography
      findings typical of the respective ion channel disease were detected in both
      patients. Closer examination of the patients' myotonic sequences occurring in
      electromyography of the relaxed muscle revealed differences that already enable
      the evaluation of the type of ion channel disease.

PMID- 29188982
TI  - Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control.

PMID- 29188983
TI  - Recent Developments in Radiotherapy.

PMID- 29188984
TI  - Treatment of tremor - deep brain stimulation as remedy for severe cases.
AB  - Tremor is a common motor disorder, in many diseases. Healthy persons may have low
      amplitude physiological action tremor without any functional handicap, contrary
      to the disabling pathologic tremor. There are numerous types of tremor, and their
      etiology is poorly known. Tremor can at best be alleviated by drug therapy, but
      the response may abate with time. Deep brain stimulation has recently been
      increasingly utilized in the treatment of drug-resistant tremor in various
      neurologic diseases.

PMID- 29188985
TI  - Is it possible to improve memory with drugs in health people?
AB  - The development of general medication for memory loss in healthy people has
      proven difficult. The brain harbors a number of parallel memory systems, which
      further involve different and separate stages of processing. The action of these
      stages is modified partly by the same mediators having, however, different
      optimum levels in distinct processes. Thus for instance stress hormones,
      powerfully supporting storage in long-term memory, will in similar concentrations
      impair implicit memory. A number of memory-enhancing drugs are available, but
      they are usually effective only individually and in tailored doses.

PMID- 29188986
TI  - Pushing the Resolving Power of Tyndall-Powell Gate Ion Mobility Spectrometry over
      100 with No Sensitivity Loss for Multiple Ion Species.
AB  - Ion gate is a key buildup for drift tube ion mobility spectrometry (IMS) and its
      combination with mass spectrometry. Bradbury-Nielsen gate, as the most commonly
      used ion gate in IMS, possesses a distinct ion mobility discrimination effect due
      to its depletion features. This impedes the scaling of the ion gate opening time
      to improve the separation capability of IMS while keeping its sensitivity for
      multiple ion species. In this work, a Tyndall-Powell gate (TPG) simply composed
      of two identical wire grids was used to develop an ion gate with nearly no ion
      mobility discrimination for IMS. Experimental results showed that the TPG
      features a gate region where the electric field for opening the gate could be
      enhanced to effectively solve the ion mobility discrimination problem related to
      it. Meanwhile, enhancing that electric field enabled the TPG-IMS to keep a
      resolving power over 106 at 100  degrees C for ion peak with a signal-to-noise
      ratio up to 800. With that TPG-IMS, baseline separation of two ion peaks, the
      hydronium and the acetone monomer peaks with a reduced mobility difference of
      only 0.04 cm2 V-1 s-1, was achieved with no sensitivity loss for the least mobile
      acetone dimer ions.

PMID- 29188987
TI  - Multifunctional Moth-Eye TiO2/PDMS Pads with High Transmittance and UV Filtering.
AB  - This work reports a facile fabrication method for constructing multifunctional
      moth-eye TiO2/polydimethylsiloxane (PDMS) pads using soft nano-imprinting
      lithography and a gas-phase-deposited thin sacrificial layer. Mesoporous TiO2
      nanoparticles act as an effective UV filter, completely blocking high-energy UVB
      light and partially blocking UVA light and forming a robust TiO2/PDMS composite
      pad by allowing the PDMS solution to easily fill the porous TiO2 network. The
      paraboloid-shaped moth-eye nanostructures provided high transparency in the
      visible spectrum and also have self-cleaning effects because of nanoroughness on
      the surface. Furthermore, we successfully achieved a desired multiscale-patterned
      surface by partially curing select regions using TiO2/PDMS pads with partial UVA
      ray blockers. The ability to fabricate multifunctional polymeric pads is
      advantageous for satisfying increasing demands for flexible and wearable
      electronics, displays, and solar cells.

PMID- 29188988
TI  - Determination of Urinary Metabolites of the Emerging UV Filter Octocrylene by
      Online-SPE-LC-MS/MS.
AB  - Octocrylene (OC) is an emerging UV filter, which is used in the majority of
      sunscreens as well as other personal care products (PCP) and consumer products.
      Its presence in various environmental matrices has been reported. However,
      information on the internal OC exposure in humans is not available, due to the
      lack of appropriate biomarkers of exposure and analytical methods. Here, we
      describe a rugged, precise, and accurate analytical method for the determination
      of three OC metabolites (ester hydrolysis and alkyl chain oxidation products) in
      human urine by stable isotope dilution analysis. Urine samples are incubated with
      beta-glucuronidase (E. coli K12) and then analyzed by liquid chromatography
      electrospray ionization-triple quadrupole-tandem mass spectrometry with online
      turbulent flow chromatography for sample cleanup and analyte enrichment (online
      SPE-LC-MS/MS). Syntheses of analytical standards, including deuterium-labeled
      internal standards, are also described. In a pilot study, we investigated the
      applicability of the metabolites as biomarkers of exposure in urine samples from
      the general population (n = 35). OC metabolites were detected in 91% of the
      samples, with the highest concentrations for three individuals having used
      sunscreen within 5 days prior to sample collection. We will apply the method in
      future human biomonitoring studies for OC exposure and risk assessment.

PMID- 29188990
TI  - Reactive Dopamine Leads to Triple Trouble in Nigral Neurons.

PMID- 29188989
TI  - Identification and Experimental Characterization of an Extremophilic Brine Pool
      Alcohol Dehydrogenase from Single Amplified Genomes.
AB  - Because only 0.01% of prokaryotic genospecies can be cultured and in situ
      observations are often impracticable, culture-independent methods are required to
      understand microbial life and harness potential applications of microbes. Here,
      we report a methodology for the production of proteins with desired functions
      based on single amplified genomes (SAGs) from unculturable species. We use this
      method to resurrect an alcohol dehydrogenase (ADH/D1) from an uncharacterized
      halo-thermophilic archaeon collected from a brine pool at the bottom of the Red
      Sea. Our crystal structure of 5,6-dihydroxy NADPH-bound ADH/D1 combined with
      biochemical analyses reveal the molecular features of its halo-thermophily, its
      unique habitat adaptations, and its possible reaction mechanism for atypical
      oxygen activation. Our strategy offers a general guide for using SAGs as a source
      for scientific and industrial investigations of "microbial dark matter."

PMID- 29188991
TI  - Self-Powered Electrostatic Filter with Enhanced Photocatalytic Degradation of
      Formaldehyde Based on Built-in Triboelectric Nanogenerators.
AB  - Recently, atmospheric pollution caused by particulate matter or volatile organic
      compounds (VOCs) has become a serious issue to threaten human health.
      Consequently, it is highly desirable to develop an efficient purifying technique
      with simple structure and low cost. In this study, by combining a triboelectric
      nanogenerator (TENG) and a photocatalysis technique, we demonstrated a concept of
      a self-powered filtering method for removing pollutants from indoor atmosphere.
      The photocatalyst P25 or Pt/P25 was embedded on the surface of polymer-coated
      stainless steel wires, and such steel wires were woven into a filtering network.
      A strong electric field can be induced on this filtering network by TENG, while
      both electrostatic adsorption effect and TENG-enhanced photocatalytic effect can
      be achieved. Rhodamine B (RhB) steam was selected as the pollutant for
      demonstration. The absorbed RhB on the filter network with TENG in 1 min was
      almost the same amount of absorption achieved in 15 min without using TENG.
      Meanwhile, the degradation of RhB was increased over 50% under the drive of TENG.
      Furthermore, such a device was applied for the degradation of formaldehyde, where
      degradation efficiency was doubled under the drive of TENG. This work extended
      the application for the TENG in self-powered electrochemistry, design and concept
      of which can be possibly applied in the field of haze governance, indoor air
      cleaning, and photocatalytic pollution removal for environmental protection.

PMID- 29188993
TI  - Programmable Peptide-Cross-Linked Nucleic Acid Nanocapsules as a Modular Platform
      for Enzyme Specific Cargo Release.
AB  - Herein we describe a modular assembly strategy for photo-cross-linking peptides
      into nucleic acid functionalized nanocapsules. The peptides embedded within the
      nanocapsules form discrete nanoscale populations capable of gating the release of
      molecular and nanoscale cargo using enzyme-substrate recognition as a triggered
      release mechanism. Using photocatalyzed thiol-yne chemistry, different peptide
      cross-linkers were effectively incorporated into the nanocapsules and screened
      against different proteases to test for degradation specificity both in vitro and
      in cell culture. By using a combination of fluorescence assays, confocal and TEM
      microscopy, the particles were shown to be highly specific for their enzyme
      targets, even between enzymes of similar protease classes. The rapid and modular
      nature of the assembly strategy has the potential to be applied to both
      intracellular and extracellular biosensing and drug delivery applications.

PMID- 29188994
TI  - Particle Manipulation Methods in Droplet Microfluidics.
AB  - This Feature describes the different particle manipulation techniques available
      in the droplet microfluidics toolbox to handle particles encapsulated inside
      droplets and to manipulate whole droplets. We address the advantages and
      disadvantages of the different techniques to guide new users.

PMID- 29188992
TI  - Tracking the Catalytic Cycle of Adenylate Kinase by Ultraviolet Photodissociation
      Mass Spectrometry.
AB  - The complex interplay of dynamic protein plasticity and specific side-chain
      interactions with substrate molecules that allows enzymes to catalyze reactions
      has yet to be fully unraveled. Top-down ultraviolet photodissociation (UVPD) mass
      spectrometry is used to track snapshots of conformational fluctuations in the
      phosphotransferase adenylate kinase (AK) throughout its active reaction cycle by
      characterization of complexes containing AK and each of four different adenosine
      phosphate ligands. Variations in efficiencies of UVPD backbone cleavages were
      consistently observed for three alpha-helices and the adenosine binding regions
      for AK complexes representing different steps of the catalytic cycle, implying
      that these stretches of the protein sample various structural microstates as the
      enzyme undergoes global open-to-closed transitions. Focusing on the
      conformational impact of recruiting or releasing the Mg2+ cofactor highlights two
      loop regions for which fragmentation increases upon UVPD, signaling an increase
      in loop flexibility as the metal cation disrupts the loop interactions with the
      substrate ligands. Additionally, the observation of holo ions and variations in
      UVPD backbone cleavage efficiency at R138 implicate this conserved active site
      residue in stabilizing the donor phosphoryl group during catalysis. This study
      showcases the utility of UVPD-MS to provide insight into conformational
      fluctuations of single residues for active enzymes.

PMID- 29188995
TI  - Midostaurin, a Natural Product-Derived Kinase Inhibitor Recently Approved for the
      Treatment of Hematological MalignanciesPublished as part of the Biochemistry
      series "Biochemistry to Bedside".

PMID- 29188997
TI  - Carbon Nanotubes as Etching Masks for the Formation of Polymer Nanostructures.
AB  - We investigate the interaction of carbon nanotubes (CNTs) embedded in a polymer
      matrix [poly(methyl methacrylate) (PMMA)] with Ar plasma, which results in the
      formation of PMMA nanostructures, as CNTs act as an etching mask. Because of the
      large differences in the Ar ion sputtering yields between CNTs and PMMA, PMMA
      lines with the width comparable to that of CNTs and as high as 20 nm (for single
      walled CNTs) or 80 nm (for multiwalled CNTs) can be obtained after repeated
      exposure of CNT/PMMA films to Ar plasma. We also follow the etching process by
      investigating changes in the IV characteristics and Raman spectra of CNTs after
      each exposure to Ar plasma, which shows progressive defect generations in CNTs
      while they maintain structural integrity long enough to act as the etching mask
      for PMMA underneath. We demonstrate that the PMMA nanostructure patterns can be
      transferred to a different polymer substrate using nanoimprinting.

PMID- 29188996
TI  - a-Factor Analogues Containing Alkyne- and Azide-Functionalized Isoprenoids Are
      Efficiently Enzymatically Processed and Retain Wild-Type Bioactivity.
AB  - Protein prenylation is a post-translational modification that involves the
      addition of one or two isoprenoid groups to the C-terminus of selected proteins
      using either farnesyl diphosphate or geranylgeranyl diphosphate. Three crucial
      enzymatic steps are involved in the processing of prenylated proteins to yield
      the final mature product. The farnesylated dodecapeptide, a-factor, is
      particularly useful for studies of protein prenylation because it requires the
      identical three-step process to generate the same C-terminal farnesylated
      cysteine methyl ester substructure present in larger farnesylated proteins.
      Recently, several groups have developed isoprenoid analogs bearing azide and
      alkyne groups that can be used in metabolic labeling experiments. Those compounds
      have proven useful for profiling prenylated proteins and also show great promise
      as tools to study how the levels of prenylated proteins vary in different disease
      models. Herein, we describe the preparation and use of prenylated a-factor
      analogs, and precursor peptides, to investigate two key questions. First, a
      factor analogues containing modified isoprenoids were prepared to evaluate
      whether the non-natural lipid group interferes with the biological activity of
      the a-factor. Second, a-factor-derived precursor peptides were synthesized to
      evaluate whether they can be efficiently processed by the yeast proteases Rce1
      and Ste24 as well as the yeast methyltransferase Ste14 to yield mature a-factor
      analogues. Taken together, the results reported here indicate that metabolic
      labeling experiments with azide- and alkyne-functionalized isoprenoids can yield
      prenylated products that are fully processed and biologically functional.
      Overall, these observations suggest that the isoprenoids studied here that
      incorporate bio-orthogonal functionality can be used in metabolic labeling
      experiments without concern that they will induce undesired physiological changes
      that may complicate data interpretation.

PMID- 29188998
TI  - Transcriptional Activity of Arsenic-Reducing Bacteria and Genes Regulated by
      Lactate and Biochar during Arsenic Transformation in Flooded Paddy Soil.
AB  - Organic substrates and biochar are important in controlling arsenic release from
      sediments and soils; however, little is known about their impact on arsenic
      reducing bacteria and genes during arsenic transformation in flooded paddy soils.
      In this study, microcosm experiments were established to profile transcriptional
      activity of As(V)-respiring gene (arrA) and arsenic resistance gene (arsC) as
      well as the associated bacteria regulated by lactate and/or biochar in anaerobic
      arsenic-contaminated paddy soils. Chemical analyses revealed that lactate as the
      organic substrate stimulated microbial reduction of As(V) and Fe(III), which was
      simultaneously promoted by lactate+biochar, due to biochar's electron shuttle
      function that facilitates electron transfer from bacteria to As(V)/Fe(III).
      Sequencing and phylogenetic analyses demonstrated that both arrA closely
      associated with Geobacter (>60%, number of identical sequences/number of the
      total sequences) and arsC related to Enterobacteriaceae (>99%) were selected by
      lactate and lactate+biochar. Compared with the lactate microcosms, transcriptions
      of the bacterial 16S rRNA gene, Geobacter spp., and Geobacter arrA and arsC genes
      were increased in the lactate+biochar microcosms, where transcript abundances of
      Geobacter and Geobacter arrA closely tracked with dissolved As(V) concentrations.
      Our findings indicated that lactate and biochar in flooded paddy soils can
      stimulate the active As(V)-respiring bacteria Geobacter species for arsenic
      reduction and release, which probably increases arsenic bioavailability to rice
      plants.

PMID- 29189000
TI  - Metal-Center-Driven Supramolecular Chirogenesis in Tweezer Amino Alcohol
      Complexes: Structural, Spectroscopic, and Theoretical Investigations.
AB  - An apparently rigid dibenzothiophene-bridged zinc(II)/magnesium(II) bisporphyrin
      host (1M) has been explored for an accurate determination of the absolute
      configuration of a large series of amino alcohols. At lower substrate
      concentration, a 1:1 sandwich complex is formed which, upon addition of excess of
      substrate, converts to the 1:2 host-guest complex with complete inversion of the
      CD exciton couplet. The intensities of the couplet vary widely just by changing
      the metal ion (Zn vs Mg) and also vary between 1:1 and 1:2 host-guest complexes.
      Crystallographic characterizations are reported here for both 1:1 sandwich and
      1:2 host-guest complexes using the same pair of host and guest, for the first
      time, which enable us to scrutinize the structural and geometrical changes
      systematically in rationalizing their optical properties. The intensity of the CD
      couplet is largely dependent on how strongly the substrate binds with the host
      and also their mode of binding. No CD couplet is observed in the spectral region
      of porphyrin absorption when substrate binds in either exo-endo or exo-exo
      fashion in the 1:2 host-guest complex. However, intermolecular H bonding between
      two encapsulated substrates in the 1:2 host-guest complex stabilizes the endo
      endo conformer in which two porphyrin macrocycles are forced to be oriented in a
      clockwise/anticlockwise direction to produce an intense CD couplet. Such an endo
      endo binding of (S)-2-aminobutan-1-ol (S-AB) has resulted in a highly intense CD
      couplet with 1Mg, while no chiroptic response was observed upon changing the
      metal to zinc, since S-AB would then bind in an exo-endo form. With an increase
      in the bulk of the substrate, the endo-endo form first transforms into an exo
      endo form which, upon further increase in the bulk of the substrate, converts
      into an exo-exo complex.

PMID- 29188999
TI  - Studies on Chemical Reactivity and Electrocatalysis of Two
      Acylmethyl(hydroxymethyl)pyridine Ligand-Containing [Fe]-Hydrogenase Models (2
      COCH2-6-HOCH2C5H3N)Fe(CO)2L (L = eta1-SCOMe, eta1-2-SC5H4N).
AB  - On the basis of preparation and characterization of [Fe]-H2ase models (2-COCH2-6
      HOCH2C5H3N)Fe(CO)2L (A, L = eta1-SCOMe; B, L = eta1-2-SC5H4N), the chemical
      reactivities of A and B with various electrophilic and nucleophilic reagents have
      been investigated, systematically. Thus, when A reacted with 1 equiv of MeCOCl in
      the presence of Et3N in MeCN to give the eta2-SCOMe-coordinated acylation product
      (2-COCH2-6-MeCO2CH2C5H3N)Fe(CO)2(eta2-SCOMe) (1), treatment of A with excess
      HBF4.Et2O in MeCN gave the cationic MeCN-coordinated complex [(2-COCH2-6
      HOCH2C5H3N)Fe(CO)2(MeCN)](BF4) (2). In addition, when 2 was treated with 1 equiv
      of 2,6-(p-4-MeC6H4)2C6H3SK or PPh3 in CH2Cl2 to give the thiophenolato- and PPh3
      substituted derivatives (2-COCH2-6-HOCH2C5H3N)Fe(CO)2[2,6-(p-MeC6H4)2C6H3S] (3)
      and [(2-COCH2-6-HOCH2C5H3N)Fe(CO)2(PPh3)](BF4) (4), treatment of B with 1 equiv
      of PMe3 or P(OMe)3 in THF afforded the phosphine- and phosphite-substituted
      complexes (2-COCH2-6-HOCH2C5H3N)(eta1-2-SC5H4N)Fe(CO)2L (5, L = PMe3; 6, L =
      P(OMe)3). Interestingly, in contrast to A, when B reacted with excess HBF4.Et2O
      in MeCN to afford the BF3 adduct [2-COCH2-6-HO(BF3)CH2C5H3N]Fe(CO)2(eta1-2
      SC5H4N) (7), reaction of B with 1 equiv of p-MeC6H4COCl in the presence of Et3N
      in MeCN gave not only the expected 2-acylmethyl-6-p-toluoyloxomethylpyridine
      containing complex (2-COCH2-6-p-MeC6H4CO2CH2C5H3N)Fe(CO)2(eta2-2-SC5H4N) (8), but
      also gave the unexpected 2-toluoyloxovinyl-6-toluoyloxomethylpyridine-containing
      complex (2-p-MeC6H4CO2C2H-6-p-MeC6H4CO2CH2C5H3N)Fe(CO)2(eta2-2-SC5H4N) (9). While
      the possible pathways for the novel reactions leading to complexes 1, 2, and 7-9
      are suggested, the structures of complexes B, 1-4, and 6-9 were unambiguously
      confirmed by X-ray crystallography. In addition, model complexes A and B have
      been found to be catalysts for proton reduction to H2 from TFA under CV
      conditions.

PMID- 29189001
TI  - Searching Online Chemical Data Repositories via the ChemAgora Portal.
AB  - ChemAgora, a web application designed and developed in the context of the "Data
      Infrastructure for Chemical Safety Assessment" (diXa) project, provides search
      capabilities to chemical data from resources available online, enabling users to
      cross-reference their search results with both regulatory chemical information
      and public chemical databases. ChemAgora, through an on-the-fly search, informs
      whether a chemical is known or not in each of the external data sources and
      provides clikable links leading to the third-party web site pages containing the
      information. The original purpose of the ChemAgora application was to correlate
      studies stored in the diXa data warehouse with available chemical data. Since the
      end of the diXa project, ChemAgora has evolved into an independent portal,
      currently accessible directly through the ChemAgora home page, with improved
      search capabilities of online data sources.

PMID- 29189002
TI  - Discovery of Novel Potent VEGFR-2 Inhibitors Exerting Significant
      Antiproliferative Activity against Cancer Cell Lines.
AB  - Computational and experimental studies were applied to the discovery of a series
      of novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors.
      Eight compounds exhibited nanomolar IC50 values against VEGFR-2, and compounds 6,
      19, 22, and 23 showed potent antiproliferative effects against several cell
      lines. Particularly, compound 23 behaved better than FDA approved drugs,
      sorafenib and sunitinib, in antiproliferative activity against cell lines related
      to all nine tumor types tested (GI50 values), and it was better or comparable in
      safety (LC50 values). Compound 23 even demonstrated a high potency on one of the
      drug-resistant cell lines (NCI/ADR-RES) responsible for ovarian cancer and cell
      lines contributing to prostate cancer, regarded as one of the VEGF/VEGFR pathway
      drug-resistant tumors. This compound is likely a promising candidate for the
      treatment of leukemia, non-small cell lung cancer (NSCLC), colon cancer, ovarian
      cancer, and breast cancer with a suitable balance of both efficacy and safety.

PMID- 29189003
TI  - Theory of FRET "Spectroscopic Ruler" for Short Distances: Application to
      Polyproline.
AB  - Forster resonance energy transfer (FRET) is an important mechanism for the
      estimation of intermolecular distances, e.g., in fluorescent labeled proteins.
      The interpretations of FRET experiments with standard Forster theory relies on
      the following approximations: (i) a point-dipole approximation (PDA) for the
      coupling between transition densities of the chromophores, (ii) a screening of
      this coupling by the inverse optical dielectric constant of the medium, and (iii)
      the assumption of fast isotropic sampling over the mutual orientations of the
      chromophores. These approximations become critical, in particular, at short
      intermolecular distances, where the PDA and the screening model become invalid
      and the variation of interchromophore distances, and not just orientations, has a
      critical influence on the excitation energy transfer. Here, we present a quantum
      chemical/electrostatic/molecular dynamics (MD) method that goes beyond all of the
      above approximations. The Poisson-TrEsp method for the ab initio/electrostatic
      calculation of excitonic couplings in a dielectric medium is combined with all
      atom molecular dynamics (MD) simulations to calculate FRET efficiencies. The
      method is applied to analyze single-molecule experiments on a polyproline helix
      of variable length labeled with Alexa dyes. Our method provides a quantitative
      explanation of the overestimation of FRET efficiencies by the standard Forster
      theory for short interchromophore distances for this system. A detailed analysis
      of the different levels of approximation that connect the present Poisson
      TrEsp/MD method with Forster theory reveals error compensation effects, between
      the PDA and the neglect of correlations in interchromophore distances and
      orientations on one hand and the neglect of static disorder in orientations and
      interchromophore distances on the other. Whereas the first two approximations are
      found to decrease the FRET efficiency, the latter two overcompensate this
      decrease and are responsible for the overestimation of the FRET efficiency by
      Forster theory.

PMID- 29189004
TI  - Quantum Chemical Studies of the Structure and Stability of N-Methylated DNA
      Nucleobase Dimers: Insights into the Mutagenic Base Pairing of Damaged DNA.
AB  - DNA is constantly under attack from exogenous and endogenous sources that modify
      the chemical structure of the nucleobases. A common type of nucleobase damage is
      N-methylation, which can result in mutagenesis. Nevertheless, these lesions are
      often repaired by the DNA repair enzyme AlkB, albeit at varying rates. Herein we
      use density functional theory (B3LYP-D3(BJ)/6-311++G(2df,2p)//B3LYP/6-31G(d,p))
      to comprehensively examine the structural and energetic properties of base pairs
      between seven nucleobase lesions resulting from N-methylation on the Watson-Crick
      (WC) binding face and each canonical nucleobase. By characterizing 105 stable
      nucleobase dimers, we provide fundamental details regarding the preferred lesion
      base pairings. Specifically, we reveal that the flexibility of the methylamino
      group resulting from methylation of an exocyclic amino substituent allows the
      2MeG, 4MeC, and 6MeA lesions to maintain a preference for canonical WC base
      pairing, which correlates with the experimentally reported lack of mutagenicity
      for these damage products. In contrast, calculated distortions in key structural
      parameters and altered binding energies for base pairs involving adducts formed
      upon methylation of a ring nitrogen (namely, 1MeG, 3MeT, 1MeA, and 3MeC) help
      rationalize the associated mutagenicity and repair efficiencies. Most
      importantly, our work provides molecular-level information about the interactions
      between N-methylated and canonical nucleobases that is critical for future large
      scale modeling of damaged DNA and enzyme-DNA complexes that strive to further
      uncover the mutagenicity and repair propensities of these detrimental lesions.

PMID- 29189006
TI  - Contrasting C- and O-Atom Reactivities of Neutral Ketone and Enolate Forms of 3
      Sulfonyloxyimino-2-methyl-1-phenyl-1-butanones.
AB  - The mechanisms of intramolecular cyclization of 3-sulfonyloxyimino-2-methyl-1
      phenyl-1-butanones (1) under basic (DABCO and t-BuOK) and acidic (AcOH and TFA)
      conditions were investigated by means of experimental and computational methods.
      The ketone, enol, and enolate forms of 1 can afford different intramolecular
      cyclization products (2, 3, 4), depending on the conditions. The results of the
      reaction of 1 under basic conditions suggest intermediacy of neutral enol (DABCO)
      and anionic enolate (t-BuOK), while the results under acidic conditions (AcOH and
      TFA) indicate involvement of neutral ketones, which exhibit reactivities arising
      from both the oxygen lone-pair electrons (O atom reactivity) and carbon sigma
      electrons (C atom reactivity). The neutral enol in DABCO afforded 2H-azirine 4.
      On the other hand, the products (isoxazole 2 and oxazole 3) generated from the
      ketone form and from the enolate form are the same, but the reaction mechanisms
      are apparently different. The results demonstrate ambident-like reactivity of
      neutral ketone in the 3-sulfonyloxyimino-2-methyl-1-phenyl-1-butanone system.

PMID- 29189005
TI  - Phytoestrogens Weaken the Blood-Milk Barrier in Lactating Mammary Epithelial
      Cells by Affecting Tight Junctions and Cell Viability.
AB  - During lactation, mammary epithelial cells (MECs) form the blood-milk barrier by
      less-permeable tight junctions (TJs) to prevent the leakage of milk components.
      Phytoestrogens affect the proliferation, differentiation, and apoptosis of MECs.
      However, it remains unclear whether phytoestrogens are involved in the blood-milk
      barrier. Therefore, we investigated the influence of phytoestrogens (coumestrol,
      genistein, and daidzein) by using an in vitro mouse-MEC-culture model. The
      results showed that coumestrol and genistein changed the expression of TJ
      proteins (claudins-3 and -4 and occludin), weakened barrier function, and reduced
      beta-casein production. Daidzein also weakened barrier function without
      inhibiting beta-casein production. Additionally, coumestrol and genistein induced
      apoptosis in MECs. These results indicate that phytoestrogens weaken the blood
      milk barrier by directly affecting TJs and the cellular viability of lactating
      MECs in different ways.

PMID- 29189007
TI  - Tin and Lead Phosphanido Complexes: Reactivity with Chalcogens.
AB  - The reactivity of tin and lead phosphanido complexes with chalogens is reported.
      The addition of sulfur to [(BDI)MPCy2] (M = Sn, Pb; BDI = CH{(CH3)CN-2,6
      iPr2C6H3}2) results in the formation of phosphinodithioates [(BDI)MSP(S)Cy2]
      regardless of the conditions; however, when selenium is added to [(BDI)MPCy2], a
      selenium insertion product, phosphinoselenoite [(BDI)MSePCy2], can be isolated.
      This compound readily reacts with additional selenium to form the
      phosphinodiselenoate complex [(BDI)MSeP(Se)Cy2]. In contrast, the addition of
      selenium to [(BDI)SnP(SiMe3)2] results in the formation of the heavy ether
      [(BDI)SnSeSiMe3]. Differences in the solution and solid-state molecular species
      of tin phosphinoselenoite and phosphinodiselenoate complexes were probed using
      multinuclear solution and solid-state NMR spectroscopy.

PMID- 29189008
TI  - Pressure-Induced Polymerization of CO2 in Lithium-Carbon Dioxide Phases.
AB  - We report the discovery of novel CO2-based networks stabilized by Li+ cations in
      solid-state phases. Our exploration of the energy landscape of the Li-CO2 binary
      phase diagram using ab initio evolutionary structure searches revealed that in
      addition to the well-characterized C2O42- oxalate in Li2C2O4 viable covalent CO2
      based nets emerge upon compression within the 0-100 GPa pressure range. Novel
      molecular units are described, such as ethene-like C2O44- in C2/m Li2(CO2),
      finite C4O86- chains in P1 Li3(CO2)2, one-dimensional polymeric forms based on
      1,4-dioxane rings in P2/c LiCO2, and the C(O-)2 moieties in Pnma Li2CO2. This
      investigation shows the oxalate motif is maintained when the concentration of
      lithium increases from 1 to 2 in LixCO2; this interesting property may have
      potential in the development of renewable Li-ion batteries. Moreover, a variety
      of metastable phases were predicted, such as the covalent CO2-based layer in P1
      Li(CO2)2.

PMID- 29189009
TI  - Synthesis of Functionalized Benzo[g]indoles and 1-Naphthols via Carbon-Carbon
      Triple Bond Breaking/Rearranging.
AB  - Novel carbon-carbon triple bond breaking and rearranging reactions of benzene
      linked allene-ynes have been established. The reactions can be selectively
      controlled toward the formation of two families of skeletally diverse
      benzo[g]indoles and 1-naphthols under mild conditions. Silver salt was found to
      efficiently promote indole annulation to give multifunctional benzo[g]indoles
      with the installation of two sulfonyl groups into the indole ring via N-S and N-F
      bond cleavage of NFSI, whereas NBS and NCS-mediated benzannulations occurred with
      the formation of dihalogenated 1-naphthols.

PMID- 29189011
TI  - Uniaxial Negative Thermal Expansion, Negative Linear Compressibility, and
      Negative Poisson's Ratio Induced by Specific Topology in Zn[Au(CN)2]2.
AB  - The well-known idea of "structure determines properties" can be understood
      profoundly in the case of hexagonal zinc dicyanometalate. Using density
      functional theory (DFT) calculations, we show the uniaxial negative thermal
      expansion (NTE) and negative linear compressibility (NLC) properties of
      Zn[Au(CN)2]2. The temperature dependence of phonon frequencies within the quasi
      harmonic approximation (QHA) is investigated. The abnormal phonon hardening
      (frequency increase on heating) is detected in the ranges of 0-225, 320-345, and
      410-430 cm-1, which can be indicative of the unusual physical properties of
      Zn[Au(CN)2]2. Due to the significance of low-energy phonon frequencies in
      Zn[Au(CN)2]2, in this work, the corresponding vibrational mode of the lowest
      frequency optical phonon at the zone center is analyzed. The specific topology of
      a springlike framework that will produce the effects of a compressed spring on
      heating and an extended spring under hydrostatic pressure is identified and leads
      to the coexistence of uniaxial-NTE and NLC behaviors in Zn[Au(CN)2]2. The
      distinguishing phonon group velocity along the a axis and c axis facilitates
      different responses for both the axes under temperature and hydrostatic pressure
      field. Through an analysis and visualization of the spatial dependence of elastic
      tensors, it is found that a negative Poisson's ratio (NPR) is presented in all
      projection planes due to the specific topology.

PMID- 29189010
TI  - Diastereoselective Synthesis of Salacinol-Type alpha-Glucosidase Inhibitors.
AB  - A facile and highly diastereoselective approach toward the synthesis of potent
      salacinol-type alpha-glucosidase inhibitors, originally isolated from plants of
      the genus "Salacia", was developed using the S-alkylation of thiosugars with
      epoxides in HFIP (~90%, dr, alpha/beta = ~ 26/1). The dr ratio of the product was
      significantly improved by the protocol as compared to that of the conventional S
      alkylation of thiosugars (dr, alpha/beta = ~ 8/1). The protocol could be used for
      gram scale synthesis of the desired compounds. The 3'-O-benzylated salacinol
      analogs, which are the most potent in vitro inhibitors to date, were synthesized
      and evaluated in vivo; all analogs suppressed blood glucose levels in maltose
      loaded mice, at levels comparable to those of the antidiabetic agent, voglibose.

PMID- 29189012
TI  - Impact of Postsynthetic Surface Modification on Photoluminescence Intermittency
      in Formamidinium Lead Bromide Perovskite Nanocrystals.
AB  - We study the origin of photoluminescence (PL) intermittency in formamidinium lead
      bromide (FAPbBr3, FA = HC(NH2)2) nanocrystals and the impact of postsynthetic
      surface treatments on the PL intermittency. Single-dot spectroscopy revealed the
      existence of different individual nanocrystals exhibiting either a blinking
      (binary on-off switching) or flickering (gradual undulation) behavior of the PL
      intermittency. Although the PL lifetimes of blinking nanocrystals clearly
      correlate with the individual absorption cross sections, those of flickering
      nanocrystals show no correlation with the absorption cross sections. This
      indicates that flickering has an extrinsic origin, which is in contrast to
      blinking. We demonstrate that the postsynthetic surface treatment with sodium
      thiocyanate improves the PL quantum yields and completely suppresses the
      flickering, while it has no significant effect on the blinking behavior. We
      conclude that the blinking is caused by Auger recombination of charged excitons,
      and the flickering is due to a temporal drift of the exciton recombination rate
      induced by surface-trapped electrons.

PMID- 29189013
TI  - Deterministic Line-Shape Programming of Silicon Nanowires for Extremely
      Stretchable Springs and Electronics.
AB  - Line-shape engineering is a key strategy to endow extra stretchability to 1D
      silicon nanowires (SiNWs) grown with self-assembly processes. We here demonstrate
      a deterministic line-shape programming of in-plane SiNWs into extremely
      stretchable springs or arbitrary 2D patterns with the aid of indium droplets that
      absorb amorphous Si precursor thin film to produce ultralong c-Si NWs along
      programmed step edges. A reliable and faithful single run growth of c-SiNWs over
      turning tracks with different local curvatures has been established, while high
      resolution transmission electron microscopy analysis reveals a high quality
      monolike crystallinity in the line-shaped engineered SiNW springs. Excitingly, in
      situ scanning electron microscopy stretching and current-voltage
      characterizations also demonstrate a superelastic and robust electric transport
      carried by the SiNW springs even under large stretching of more than 200%. We
      suggest that this highly reliable line-shape programming approach holds a strong
      promise to extend the mature c-Si technology into the development of a new
      generation of high performance biofriendly and stretchable electronics.

PMID- 29189014
TI  - Total Synthesis of Four Isomers of the Proposed Structures of Cryptorigidifoliol
      K.
AB  - The first asymmetric convergent total synthesis of four isomers of proposed
      structures of cryptorigidifoliol K (1a, 1b, 1c, and 1d) has been achieved from
      commercially available starting materials. The key steps in this synthesis
      involve tandem isomerization followed by a C-O and C-C bond-forming reaction for
      the construction of trans-2,6-disubstituted dihydropyran, iodolactonization,
      isomerization of terminal alkene, and cross-metathesis reaction. The large
      discrepancies in the spectroscopic data (1H NMR) of synthetic cryptorigidifoliol
      K from the natural product suggest that the structure of the natural
      cryptorigidifoliol K requires revision.

PMID- 29189015
TI  - Reversibly Tunable White-Light Emissions of Styrylpyridiniums with Cucurbiturils
      in Aqueous Solution.
AB  - The different excimer emissions based on a series of host-guest complexes of
      dipolar dyes styrylpyridiniums (An and Bn) with cucurbit[n]urils (CB[n]) are
      reported. The syn- and anti- excimers due to the opposite stacking orientations
      have been well investigated both in experiments and DFT calculations.
      Furthermore, reversibly color-tunable luminescent supramolecular assemblies
      including near white-light emission with CIE coordinates (0.32, 0.29) were
      achieved by competitive inclusion of An-CB[7] with ADA.

PMID- 29189016
TI  - Antiprotozoal Spirombandakamines A1 and A2, Fused Naphthylisoquinoline Dimers
      from a Congolese Ancistrocladus Plant.
AB  - From the leaves of a yet undescribed Congolese Ancistrocladus species, two novel
      naphthylisoquinoline dimers, spirombandakamines A1 (1) and A2 (2), were isolated,
      together with a new, but "classical" dimer, mbandakamine B2 (3). The cage-like
      stereostructures of 1 and 2 were established by combining spectroscopic,
      chemical, and chiroptical methods with quantum-chemical ECD calculations. Their
      unique molecular frameworks may originate from "open-chain" dimers, such as 3, by
      an oxidation-induced cascade of reactions. They possess strong antiprotozoal
      properties.

PMID- 29189017
TI  - The dorsomedial striatum mediates Pavlovian appetitive conditioning and food
      consumption.
AB  - The dorsomedial striatum (DMS) is an important sensorimotor region mediating the
      acquisition of goal-directed instrumental reward learning and behavioral
      flexibility. However, whether the DMS also regulates Pavlovian cue-food learning
      is less clear. The current study used excitotoxic lesions to determine whether
      the DMS is critical in Pavlovian appetitive learning and behavior, using
      discriminative conditioning and reversal paradigms. The results showed that DMS
      lesions transiently retarded cue-food learning and subsequent reversal of this
      learning. Rats with DMS lesions selectively attenuated responding to a food cue
      but not a control cue, early in training, suggesting the DMS is involved when
      initial associations are formed. Similarly, initial reversal learning was
      attenuated in rats with DMS lesions, which suggests impaired flexibility to
      adjust behavior when the cue meaning is reversed. We also examined the effect of
      DMS lesions on food intake during tests with access to a highly palatable food
      along with standard chow diet. Rats with DMS lesions showed an altered pattern of
      intake, with an initial reduction in high-fat diet followed by an increase in
      chow consumption. These results demonstrate that the DMS has a role in mediating
      cue-food learning and its subsequent reversal, as well as changes in food intake
      when a choice is provided. Together, these results demonstrate the DMS is
      involved in reward associative learning and reward consumption, when behavioral
      flexibility is needed to adjust responding or consumption to match the current
      value. (PsycINFO Database Record

PMID- 29189018
TI  - The application of a rodent-based Morris water maze (MWM) protocol to an
      investigation of age-related differences in human spatial learning.
AB  - The current study applied a rodent-based Morris water maze (MWM) protocol to an
      investigation of search performance differences between young and older adult
      humans. To investigate whether similar age-related decline in search performance
      could be seen in humans based on the rodent-based protocol, we implemented a
      virtual MWM (vMWM) that has characteristics similar to those of the MWM used in
      previous studies of spatial learning in mice. Through the use of a proximity to
      platform measure, robust differences were found between healthy young and older
      adults in search performance. After dividing older adults into good and poor
      performers based on a median split of their corrected cumulative proximity
      values, the age effects in place learning were found to be largely related to
      search performance differences between the young and poor-performing older
      adults. When compared with the young, poor-performing older adults exhibited
      significantly higher proximity values in 83% of 24 place trials and overall in
      the probe trials that assessed spatial learning in the absence of the hidden
      platform. In contrast, good-performing older adults exhibited patterns of search
      performance that were comparable with that of the younger adults in most place
      and probe trials. Taken together, our findings suggest that the low search
      accuracy in poor-performing older adults stemmed from potential differences in
      strategy selection, differences in assumptions or expectations of task demands,
      as well as possible underlying functional and/or structural changes in the brain
      regions involved in vMWM search performance. (PsycINFO Database Record

PMID- 29189019
TI  - Across sex and age: Learning and memory and patterns of avian hippocampal gene
      expression.
AB  - Age-related decrements in cognitive ability have been proposed to stem from
      deteriorating function of the hippocampus. Many birds are long lived, especially
      for their relatively small body mass and elevated metabolism, making them a
      unique model of resilience to aging. Nevertheless, little is known about avian
      age-related changes in cognition and hippocampal physiology. We studied spatial
      cognition and hippocampal expression of the age-related gene, Apolipoprotein D
      (ApoD), and the immediate early gene Egr-1 in zebra finches at various
      developmental time points. In a first experiment, middle-aged adult males
      outperformed middle-aged females in learning correct food locations in a four-arm
      maze, but all birds remembered the task equally well after a 5- or 10-day delay.
      In a second experiment comparing young and old birds, aged birds showed minimal
      evidence for deterioration in spatial cognition or motivation relative to young
      birds, except that aged females showed less rapid gains in accuracy during
      spatial learning than young females. These findings indicate that sex differences
      in hippocampus-dependent spatial learning and decline with age are
      phylogenetically conserved. With respect to hippocampal gene expression, adult
      females expressed Egr-1 at significantly greater levels than males after memory
      retrieval, perhaps reflecting a neurobiological compensation. Contrary to
      mammals, ApoD expression was elevated in young zebra finches compared with aged
      birds. This may explain the near absence of decrements in spatial memory due to
      age, possibly indicating an alternative mechanism of managing oxidative stress in
      aged birds. (PsycINFO Database Record

PMID- 29189020
TI  - Effect of social isolation on anxiety-related behaviors, cortisol, and monoamines
      in adult zebrafish.
AB  - Social isolation can be used to study behavioral, neural, and hormonal mechanisms
      that regulate interactions in social animals. Although isolation effects have
      been reported in social mammals and various fish species, systematic studies with
      isolated zebrafish are rare. Here, the authors examined behavior (social and
      nonsocial), physiological stress (whole-body cortisol levels), and neurochemicals
      (serotonin, dopamine, and their metabolites), following acute and chronic social
      isolation in adult zebrafish. To observe how isolated fish respond behaviorally
      to social stimuli, they exposed zebrafish to live conspecifics or animated images
      after acute (24 hr) or chronic (6 months) social isolation. The authors observed
      that isolation did not affect locomotor activity, but acute isolation had weak
      nonsignificant anxiogenic effects in adult zebrafish. They also found that all
      isolated fish responded to both live and animated social stimuli, and the stress
      hormone, cortisol was lower in chronically isolated fish. Finally, neurochemical
      analyses showed that serotonin levels increased when fish were exposed to social
      stimulus after acute isolation, but its metabolite 5HIAA decreased in response to
      social stimulus following both acute and chronic isolation. Levels of both
      dopamine and its metabolite DOPAC were also reduced in fish exposed to social
      stimulus after acute and chronic isolation. Overall, these results show that
      isolation in zebrafish is an effective tool to study fundamental mechanisms
      controlling social interaction at behavioral and physiological levels. (PsycINFO
      Database Record

PMID- 29189021
TI  - Effects of antismoking media on college students' smoking-related beliefs and
      intentions.
AB  - Ecological momentary assessment was used to examine immediate changes in 87
      college students' smoking-related attitudes, beliefs, and intentions as a joint
      function of their exposure to antismoking media and smoking status. Students (37
      never smokers, 41 experimental smokers, and 9 current intermittent smokers)
      carried handheld data-collection devices for 3 weeks to record naturally
      occurring exposures to antismoking media and respond to investigator-initiated
      control prompts. At each reported exposure to antismoking media and each control
      prompt, participants reported their smoking-related attitudes, perceptions of the
      prevalence of smoking among their peers, resistance self-efficacy, and intentions
      to smoke. Mixed-effects regression was used to compare responses between
      encounters with antismoking media and control prompts. Experimental smokers
      reported weaker intentions to smoke and greater resistance self-efficacy at
      moments of exposure to antismoking media than at control prompts. Regardless of
      smoking experience, participants reported higher perceived prevalence of smoking
      at times of exposure to antismoking media than at control prompts. These findings
      generally support the value of antismoking media messages for shifting the
      beliefs and intentions of experimental smokers, who are at high risk for becoming
      committed regular smokers. (PsycINFO Database Record

PMID- 29189022
TI  - Using counterattitudinal advocacy to change drinking: A pilot study.
AB  - The persistence of risky drinking among young adults in college calls for
      continued efforts to prevent alcohol-related harms. This study tested a novel
      prevention strategy targeting a specific mechanism of change: creating attitude
      behavior dissonance. Informed by an extensive literature showing strong and
      consistent associations between alcohol attitudes and drinking behavior, we
      adapted a brief counterattitudinal advocacy (CAA) manipulation to the alcohol
      prevention context. We conducted a small randomized controlled trial with 49
      heavy-drinking students who reported drinking 4/5 drinks in 1 sitting
      (female/male, respectively) and endorsed >=2 alcohol-related consequences in the
      previous month. Participants were randomly assigned to 1 of 2 conditions (CAA or
      control). We examined the number of words written in response to the prompts,
      evaluated adherence to the core theoretical principles used in CAA, and
      calculated between- and within-group effect sizes on preliminary outcomes
      (drinking intentions and alcohol consumption). We found that participants in the
      CAA condition wrote more, and the experience was perceived as consistent with CAA
      theory. The between-group effect sizes on drinking intentions and drinks per week
      were d = .36 and d = .27, respectively, and the within-group effect size for
      drinks per week was d = .83 for those in the CAA condition. Overall, the results
      of this pilot study support the feasibility and acceptability of CAA-based
      alcohol use interventions. This study represents a promising first step in
      adapting CAA-based interventions for use in the alcohol use domain. (PsycINFO
      Database Record

PMID- 29189024
TI  - Extension to one week of verbal memory consolidation assessment.
AB  - OBJECTIVE: Although impairments of long-term recall affect everyday life, they
      may be missed by standard delayed recall tests, which typically assess the
      ability to retain new information within a few minutes, without encompassing the
      consolidation process. We adapted a verbal memory test to evaluate long-term
      memory consolidation in healthy volunteers. METHOD: A sample of 238 participants
      (M = 42.23 years old, SD = 16.45) was administered an adapted version of the
      French RL/RI-16 (Van der Linden & the members of GREMEM, 2004), the One-Week Free
      and Cued Selective Reminding Test-word version, in which special feature relies
      on a 30-min and a 1-week-delayed recall after encoding. We proposed normative
      data on 4 indicators, depending on participants' own performance during the test,
      to measure their encoding, storage and consolidation abilities, with a method
      using an ascendant step-by-step linear regression model and a percentile
      procedure. RESULTS: Results showed a better performance in women than in men for
      encoding and cueing scores (p < .01 and p < .05, respectively). We also
      highlighted an increase of the forgetting score according to the recall delay
      after encoding (30 min vs. 7 days; Z = 12.49, p < .001), the forgetting
      percentage 7 days after encoding being largely influenced by participants' age
      and gender (F[2, 236] = 248.1, p < .001; adjusted R2 = 67%). CONCLUSIONS: This
      study emphasized the role of demographic factors on long-term memory
      consolidation. The demographically adjusted normative data we provide for the One
      Week Free and Cued Selective Reminding Test-word version make it a sensitive tool
      for long-term memory consolidation assessment in clinical and forensic practice.
      (PsycINFO Database Record

PMID- 29189023
TI  - The intergenerational transmission of cannabis use: Associations between parental
      history of cannabis use and cannabis use disorder, low positive parenting, and
      offspring cannabis use.
AB  - Parental cannabis use disorder (CUD) and low positive parenting (monitoring,
      support, and consistency) are risk factors for adolescent cannabis use. However,
      it is unclear whether parental cannabis use without CUD is sufficient to increase
      risk for low positive parenting and adolescent cannabis use. Additionally,
      parents may not treat each of their adolescents the same, and risk for adolescent
      cannabis use may increase as a result of low levels of positive parenting in
      families or low positive parenting unique to each adolescent. The current study
      prospectively tested low positive parenting as a mediator of the relation between
      parental cannabis use history (with parental cannabis use and CUD considered
      separately) and adolescent cannabis use at the family level and individual level.
      Participants were 363 adolescents from a multigenerational longitudinal study who
      reported on positive parenting when they were ages 9-16 (M = 11.6, SD = 1.40) and
      on cannabis use when they were ages 13-19 (M = 16.3, SD = 1.84). Parents reported
      on their own cannabis use and CUD. Results showed that parental CUD was
      associated with adolescent cannabis use (OR = 3.62, p = .047) but parental
      cannabis use without CUD was not, and only parental CUD predicted low positive
      parenting (B = -0.28, p < .05). Average levels of low positive parenting within a
      family partially mediated the association between parental CUD and offspring
      cannabis use. These findings suggest parental cannabis use alone may not impair
      parenting, but parental use that meets criteria for CUD does impair parenting.
      Additionally, average levels of positive parenting in families may be a mechanism
      underlying the intergenerational transmission of cannabis use. (PsycINFO Database
      Record

PMID- 29189025
TI  - The Interplay of Personality and Functional Health in Old and Very Old Age:
      Dynamic Within-Person Interrelations Across up to 13 Years.
AB  - Conceptual and empirical work has long suggested that personality and health are
      closely intertwined later in life. Little is known, however, about the nature and
      direction of time-ordered associations between the 2 domains within-persons. We
      applied continuous time auto- and cross-effects models to up to 6 waves of 13
      year longitudinal data from the Berlin Aging Study (N = 516, M = 84.92, SD =
      8.66, age range 70 to 103) and examined time-ordered relations between
      personality traits (i.e., extraversion and neuroticism) and performance-based
      indicators of functional health (i.e., physical and sensory functioning) in late
      life. Consistent with proposals to distinguish the young-old (age 70 to 84) from
      the oldest-old (aged 85+) in later life, results suggest that predictive effects
      of neuroticism on functional health are stronger in younger as compared with
      older individuals. In contrast, health decrements precede and predict change in
      neuroticism in the oldest-old more strongly as compared with the young-old. In
      addition, we found that decreases in extraversion predict subsequent decreases in
      functional health and vice versa, with effects being equally pronounced among
      younger and older participants. Furthermore, by employing continuous time models
      we could demonstrate that the magnitude of these effects varies depending upon
      the time interval under consideration. These findings suggest that personality
      and functional health are closely intertwined in old and very old age, and that
      the nature of time-ordered associations differs between traits and age period. We
      discuss conceptual and practical implications. (PsycINFO Database Record

PMID- 29189027
TI  - Goal versus trait explanations: Causal attributions beyond the trait-situation
      dichotomy.
AB  - In 4 studies, we show that two behavioral dimensions specified in Kelley's (1967)
      model of attribution, consistency and distinctiveness of behaviors, determine
      perceivers' likelihood to explain others' behaviors in terms of their goals
      versus traits. Participants tended to attribute the cause of others' behaviors to
      their goals (vs. traits and other characteristics) when behaviors were
      characterized by high distinctiveness (Study 1A & 1B) or low consistency (Study
      2). On the other hand, traits were ascribed as predominant causal explanations
      when behaviors had low distinctiveness or high consistency. Study 3 investigated
      the combined effect of those behavioral dimensions on causal attributions and
      showed that behaviors with high distinctiveness and consistency as well as low
      distinctiveness and consistency trigger goal attributions. We discuss the
      implications of the present research in terms of going beyond the dominant
      approach of trait-situation dichotomy in attribution research. (PsycINFO Database
      Record

PMID- 29189026
TI  - The ebbs and flows of attachment: Within-person variation in attachment undermine
      secure individuals' relationship wellbeing across time.
AB  - Although attachment security is relatively stable over time, individuals do
      experience significant within-person variation in their attachment security
      across time. No research to date, however, has assessed the relational
      consequences of within-person variation (fluctuations) in attachment security
      toward a specific attachment figure. Study 1 (N = 409) first examined whether
      attachment security was associated with individuals' expectations that their
      current intimate relationship would be stable and consistent over time (vs.
      inconsistent and unstable). Studies 2 and 3 extended this by examining the
      prevalence and consequences of actual within-person variation (fluctuations) in
      relationship-specific attachment security toward an intimate partner in 2
      multiwave longitudinal studies that assessed individuals (Study 2, N = 324) and
      couples (Study 3, N = 171 dyads). The results indicate that secure individuals
      (those low in attachment anxiety or attachment avoidance) expect their current
      relationship to remain relatively stable and consistent over time (Study 1).
      However, Studies 2 and 3 demonstrated that most individuals do experience
      fluctuations in their relationship-specific attachment security. Moreover,
      greater fluctuations predict declines in relationship satisfaction (Studies 2 and
      3) and increases in relationship distress (Study 3) over time, but primarily for
      secure individuals (those low in baseline attachment anxiety or attachment
      avoidance). This set of findings highlight the importance of examining within
      person fluctuations in attachment security, which are associated with declines in
      trajectories of relationship wellbeing, particularly for secure individuals who
      anticipate greater stability in their relationships. (PsycINFO Database Record

PMID- 29189028
TI  - Introduction to the special section on sexual and gender minority health.
AB  - The field of sexual and gender minority health has advanced exponentially in the
      past decade. The Journal of Consulting and Clinical Psychology (JCCP) has made
      important strides in publishing work on sexual and gender minority health.
      Although the following set of articles was not originally planned as a special
      section, most of the articles address, in some way, sexual and gender minority
      specific stressors such as perceived or overt stigma and/or the higher risk for
      emotional and substance use problems facing this population. Together, the papers
      in this section are models of some of the best work being conducted on sexual and
      gender minority health. Not only do they address significant problems, they do so
      in large, nonoverlapping samples, using novel and strong methodologies. (PsycINFO
      Database Record

PMID- 29189030
TI  - A weekly diary study of minority stress, coping, and internalizing symptoms among
      gay men.
AB  - OBJECTIVE: Research has demonstrated that gay men are at increased risk for
      internalizing disorders compared with heterosexual men and that minority
      stressors are risk factors. However, the mechanisms underlying the associations
      between minority stressors and internalizing symptoms remain unclear. The current
      study examined coping strategies (active and disengaged coping) as mediators of
      the associations between minority stressors (internalized homonegativity [IH] and
      rejection sensitivity [RS]) and internalizing symptoms. METHOD: A sample of 147
      gay men completed a baseline questionnaire and weekly questionnaires for seven
      consecutive weeks. RESULTS: At the between-person level, higher IH and RS were
      associated with higher disengaged coping, but not active coping. In turn, higher
      disengaged coping was associated with higher internalizing symptoms. Disengaged
      coping mediated the between-person association between IH and internalizing
      symptoms. At the within-person level, higher IH and RS were associated with
      higher disengaged coping, which, in turn, was associated with higher
      internalizing symptoms. Higher RS was also associated with higher active coping.
      Disengaged coping mediated the within-person associations between both minority
      stressors and internalizing symptoms. Of note, some associations with IH became
      nonsignificant controlling for RS, suggesting that the latter has a stronger
      influence on coping and internalizing symptoms. CONCLUSIONS: Findings demonstrate
      that gay men's negative thoughts and feelings about their sexual orientation and
      anxious expectations of rejection vary from week to week and this weekly
      fluctuation has an impact on mental health. Further, findings implicate
      disengaged coping as a mechanism through which minority stressors influence
      internalizing symptoms. (PsycINFO Database Record

PMID- 29189029
TI  - Ecological momentary assessment of daily discrimination experiences and nicotine,
      alcohol, and drug use among sexual and gender minority individuals.
AB  - OBJECTIVE: Sexual and gender minority (SGM) individuals experience elevated rates
      of minority stress, which has been linked to higher rates of nicotine and
      substance use. Research on this disparity to date is largely predicated on
      methodology that is insensitive to within day SGM-based discrimination
      experiences, or their relation to momentary nicotine and substance use risk. We
      address this knowledge gap in the current study using ecological momentary
      assessment (EMA). METHOD: Fifty SGM individuals, between 18 and 45 years of age,
      were recruited from an inland northwestern university, regardless of their
      nicotine or substance use history, and invited to participate in an EMA study.
      Each were prompted to provide data, six times daily (between 10:00 a.m. and 10:00
      p.m.) for 14 days, regarding SGM-based discrimination, other forms of
      mistreatment, and nicotine, drug, and alcohol use since their last prompt.
      RESULTS: Discrimination experiences that occurred since individuals' last
      measurement prompt were associated with greater odds of nicotine and substance
      use during the same measurement window. Substance use was also more likely to
      occur in relation to discrimination reported two measurements prior in lagged
      models. Relative to other forms of mistreatment, discrimination effects were
      consistently larger in magnitude and became stronger throughout the day/evening.
      CONCLUSION: This study adds to existing minority stress research by highlighting
      the both immediate and delayed correlates of daily SGM-based discrimination
      experiences. These results also contribute to our understanding of daily stress
      processes and provide insight into ways we might mitigate these effects using
      real-time monitoring and intervention technology. (PsycINFO Database Record

PMID- 29189031
TI  - "Memory support strategies and bundles: A pathway to improving cognitive therapy
      for depression?": Correction to Dong, Lee, and Harvey (2017).
AB  - : Reports an error in "Memory support strategies and bundles: A pathway to
      improving cognitive therapy for depression" by Lu Dong, Jason Y. Lee and Allison
      G. Harvey (Journal of Consulting and Clinical Psychology, 2017[Mar], Vol 85[3],
      187-199). In the article, there was an error in Table 2 of the Results. In Table
      2, the MS summary scores of the Total amount of MS are missing six descriptive
      statistics. They should have read as: 13.50, 8.54, 23, 18.32, 8.83, 23. The
      corrected table is included. (The following abstract of the original article
      appeared in record 2017-07144-001.) Objective: Therapist use of memory support
      (MS) alongside treatment-as-usual, with the goal of enhancing patient recall of
      treatment contents, has been of recent interest as a novel pathway to improve
      treatment outcome. The memory support intervention (MSI) involves treatment
      providers' using 8 specific MS strategies to promote patient memory for
      treatment. The present study examines to what extent therapist use of MS
      strategies and bundles improves patient recall of treatment contents and
      treatment outcome. METHOD: The data were drawn from a pilot RCT reported
      elsewhere. Participants were 48 adults (mean age = 44.27 years, 29 females) with
      major depressive disorder (MDD), randomized to receive 14 sessions of either CT +
      Memory Support (n = 25) or CT-as-usual (n = 23). Therapist use of MS was coded
      using the Memory Support Rating Scale. Patient memory and treatment outcomes were
      assessed at baseline, midtreatment (patient recall only), posttreatment, and 6
      month follow-up. RESULTS: Participants in CT + Memory Support received
      significantly higher amount of MS relative to CT-as-usual. Although not reaching
      statistical significance, small-to-medium effects were observed between MS
      strategies and patient recall in the expected direction. Although MS variables
      were not significantly associated with changes in continuous depressive symptoms,
      MS was associated with better global functioning. MS also exhibited small to
      medium effects on treatment response and recurrence in the expected direction but
      not on remission, though these effects did not reach statistical significance.
      CONCLUSIONS: These results provide initial empirical evidence supporting an
      active method for therapists to implement MS strategies. (PsycINFO Database
      Record

PMID- 29189033
TI  - Comparing treatment response between LGBQ and heterosexual individuals attending
      a CBT- and DBT-skills-based partial hospital.
AB  - OBJECTIVE: Despite a greater need for mental health treatment in individuals
      identifying as lesbian, gay, bisexual, queer, and other sexual minority
      identities (LGBQ+), no prior study has examined mental health treatment outcomes
      for LGBQ+ populations receiving standard care. We compared individuals
      identifying as LGBQ+ or heterosexual on treatment outcomes following a partial
      hospital program based on cognitive behavioral therapy (CBT) and dialectical
      behavior therapy (DBT). METHOD: A total of 441 participants (19% LGBQ+; mean age
      = 34.42 years; 56% female, 42% male, 2% nonbinary) attending a partial hospital
      program completed measures at admission and discharge as part of standard care.
      We compared LGBQ+ and heterosexual individuals on symptom outcomes (24-item
      Behavior and Symptom Identification Scale, 7-item Generalized Anxiety Disorder
      Scale, 9-item Patient Health Questionnaire), program dropout due to inpatient
      hospitalization, clinical global improvement, and perceived quality of care,
      controlling for baseline characteristics using propensity score adjustment.
      RESULTS: Controlling for baseline demographic and clinical variables and a 10%
      false discovery rate, LGBQ+ and heterosexual individuals did not differ on
      treatment outcomes. However, when examining sexual identity subgroups, bisexual
      individuals reported more self-injurious and suicidal thoughts and worse
      perceptions of care at posttreatment compared to all other sexual identities.
      CONCLUSIONS: Findings support the comparable effectiveness of CBT- and DBT-skills
      based hospital treatment for LGBQ+ and heterosexual individuals overall but
      suggest specific treatment disparities for bisexual individuals. Future research
      is needed to establish the effectiveness of traditional evidence-based treatment
      in other settings and to determine whether LGBQ+ affirmative treatments for
      specific LGBQ+ subgroups are superior to traditional treatments. (PsycINFO
      Database Record

PMID- 29189034
TI  - Unique effects of setting goals on behavior change: Systematic review and meta
      analysis.
AB  - OBJECTIVE: Goal setting is a common feature of behavior change interventions, but
      it is unclear when goal setting is optimally effective. The aims of this
      systematic review and meta-analysis were to evaluate: (a) the unique effects of
      goal setting on behavior change, and (b) under what circumstances and for whom
      goal setting works best. METHOD: Four databases were searched for articles that
      assessed the unique effects of goal setting on behavior change using randomized
      controlled trials. One-hundred and 41 papers were identified from which 384
      effect sizes (N = 16,523) were extracted and analyzed. A moderator analysis of
      sample characteristics, intervention characteristics, inclusion of other behavior
      change techniques, study design and delivery, quality of study, outcome measures,
      and behavior targeted was conducted. RESULTS: A random effects model indicated a
      small positive unique effect of goal setting across a range of behaviors, d = .34
      (CI [.28, .41]). Moderator analyses indicated that goal setting was particularly
      effective if the goal was: (a) difficult, (b) set publicly, and (c) was a group
      goal. There was weaker evidence that goal setting was more effective when paired
      with external monitoring of the behavior/outcome by others without feedback and
      delivered face-to-face. CONCLUSIONS: Goal setting is an effective behavior change
      technique that has the potential to be considered a fundamental component of
      successful interventions. The present review adds novel insights into the means
      by which goal setting might be augmented to maximize behavior change and sets the
      agenda for future programs of research. (PsycINFO Database Record

PMID- 29189032
TI  - Applying network analysis to psychological comorbidity and health behavior:
      Depression, PTSD, and sexual risk in sexual minority men with trauma histories.
AB  - OBJECTIVE: High rates of depression and posttraumatic stress disorder (PTSD)
      contribute to sexual risk, particularly in men who have sex with men (MSM) who
      have experienced childhood sexual abuse. The comorbidity between depression and
      PTSD and mechanisms by which they contribute to sexual risk in MSM remain
      unclear. This study sought to demonstrate the feasibility and utility of a
      network approach to (a) characterize symptom interconnections between depression
      and PTSD in MSM, (b) identify specific symptoms related to sexual risk behavior,
      and (c) compare symptom networks across groups at different levels of risk.
      METHOD: Cross-sectional baseline data were collected from 296 HIV-negative urban
      MSM as part of a multisite randomized intervention trial. Symptoms of depression
      and PTSD were self-reported along with sexual risk behavior. Analyses were
      performed in R using regularized partial correlation network modeling. RESULTS:
      Network analyses revealed complex associations between depression and PTSD
      symptoms and in relation to sexual risk behavior. While symptoms clustered within
      their respective disorders, depression and PTSD were connected at key symptom
      nodes (e.g., sleep, concentration). Specific symptoms (e.g., avoiding thoughts
      and feelings) were linked to sexual risk behavior. Network comparisons across
      risk groups suggested avoidant processes could be more readily activated in
      higher-risk individuals, whereas hyperarousal symptoms may be more salient and
      protective for lower-risk individuals. CONCLUSIONS: This study is one of the
      earliest network analyses of depression and PTSD, and first to extend this
      inquiry to health behavior. Symptom-level investigations may clarify mechanisms
      underlying psychological comorbidity and behavioral risk in MSM and refine
      targets for intervention/prevention. (PsycINFO Database Record

PMID- 29189036
TI  - Identity-specific motivation: How distinct identities direct self-regulation
      across distinct situations.
AB  - Research on self-regulation has traditionally emphasized that people's thoughts
      and actions are guided by either (a) domain-general motivations that emerge from
      a cumulative history of life experiences, or (b) situation-specific motivations
      that emerge in immediate response to the incentives present in a particular
      context. However, more recent studies have illustrated the importance of
      understanding the interplay between such domain-general and situation-specific
      motivations across the types of contexts people regularly encounter. The present
      research, therefore, expands existing perspectives on self-regulation by
      investigating how people's identities-the internalized roles, relationships, and
      social group memberships that define who they are-systemically guide when and how
      different domain-general motivations are activated within specific types of
      situations. Using the motivational framework described by regulatory focus theory
      (Higgins, 1997), Studies 1 and 2 demonstrate that people indeed have distinct,
      identity-specific motivations that uniquely influence their current self
      regulation when such identities are active. Studies 3-5 then begin to explore how
      identity-specific motivations are situated within people's larger self-concept.
      Studies 3a and 3b demonstrate that the less compatible people's specific
      identities, the more distinct are the motivations connected to those identities.
      Studies 4-5 then provide some initial, suggestive evidence that identity-specific
      motivations are not a separate, superordinate feature of people's identities that
      then alter how they pursue any subordinate, identity-relevant traits, but instead
      that such motivations emerge from the cumulative motivational significance of the
      subordinate traits to which the identities themselves become attached.
      Implications for understanding the role of the self-concept in self-regulation
      are discussed. (PsycINFO Database Record

PMID- 29189035
TI  - Processes of change after a sudden gain and relation to treatment outcome
      Evidence for an upward spiral.
AB  - OBJECTIVE: Sudden gains are sudden symptom improvements from 1 psychotherapy
      session to the next. This study investigates the processes that may facilitate
      treatment outcome after a sudden gain occurred. METHOD: A sample of 211 depressed
      patients who underwent cognitive-behavioral therapy was analyzed. Sudden gains
      were identified using a session-by-session self-report symptom measure. Patient
      ratings of general change factors (therapeutic alliance; coping skills) in the
      sessions before and after a sudden gain were investigated as predictors of
      outcome. Propensity score matching was used to compare sudden gain patients with
      similar patients who did not experience a sudden gain. RESULTS: Therapeutic
      alliance and coping skills increased in the postgain sessions. There were no
      comparable processes of change among patients without sudden gains. The
      therapeutic alliance was found to moderate the association between sudden gains
      and treatment outcome. CONCLUSION: Results suggest that sudden gains trigger
      change factors that facilitate the association between gains and treatment
      outcome. Patient-therapist dyads should work with sudden gains to consolidate
      symptom relief. (PsycINFO Database Record

PMID- 29189037
TI  - Home alone: Why people believe others' social lives are richer than their own.
AB  - Although decades of research show that people tend to see themselves in the best
      possible light, we present evidence that people have a surprisingly grim outlook
      on their social lives. In 11 studies (N = 3,293; including 3 preregistered), we
      find that most people think that others lead richer and more active social lives
      than they do themselves. We show that this bias holds across multiple populations
      (college students, MTurk respondents, shoppers at a local mall, and participants
      from a large, income-stratified online panel), correlates strongly with well
      being, and is particularly acute for social activities (e.g., the number of
      parties one attends or proximity to the "inner circle" of one's social sphere).
      We argue that this pessimistic bias stems from the fact that trendsetters and
      socialites come most easily to mind as a standard of comparison and show that
      reducing the availability of extremely social people eliminates this bias. We
      conclude by discussing implications for research on social comparison and self
      enhancement. (PsycINFO Database Record

PMID- 29189038
TI  - Effect of personality on oral health-related quality of life in undergraduates.
AB  - OBJECTIVES: To evaluate the effects of personality traits and other variables on
      oral health-related quality of life (OHRQoL) of Chinese undergraduates aged 17 to
      24 years with no history of orthodontic treatment. MATERIALS AND METHODS: A total
      of 443 undergraduate students aged 17 to 24 years were selected and completed a
      two-section questionnaire: the Eysenck Personality Questionnaire Short Scale
      Chinese version and the Oral Health Impact Profile-14 Chinese version (OHIP-14).
      Malocclusion severity was assessed via clinical examination using the dental
      health component (DHC) and esthetic component of the Index of Orthodontic
      Treatment Need (IOTN). Severe dentofacial deformities that required orthognathic
      surgery were excluded. RESULTS: The total and all dichotomized OHIP-14 dimensions
      correlated closely with the neuroticism personality traits ( P < .001). The total
      and some subscales of OHIP-14 were related with psychoticism. Women had higher
      OHIP-14 scores than men, especially in the normal occlusion group. Nevertheless,
      men with more severe malocclusions had higher scores that were similar to those
      of women. OHRQoL was significantly different between the major of dentistry and
      other majors. CONCLUSIONS: Personality affects comprehensive OHRQoL, and the most
      significant predictor is neuroticism. Female young adults have worse OHRQoL than
      male young adults, especially among those with mild malocclusion.

PMID- 29189039
TI  - Reliability of three-dimensional anterior cranial base superimposition methods
      for assessment of overall hard tissue changes: A systematic review.
AB  - OBJECTIVE: The purpose of this systematic review was to synthesize the available
      literature concerning the reliability of three-dimensional superimposition
      methods when assessing changes in craniofacial hard tissues. MATERIALS AND
      METHODS: Four electronic databases were searched. Two authors independently
      reviewed potentially relevant articles for eligibility. Clinical trials, cohort,
      case-control, and cross-sectional studies that evaluated the reliability of three
      dimensional superimposition methods on the anterior cranial base were included.
      RESULTS: Six studies fulfilled the inclusion criteria. Four studies used the
      voxel-based registration method, one used the landmark-based method and one used
      the surface-based method. Regarding reliability, the voxel-based studies showed
      on average a difference of 0.5 mm or less between images. The optimized analysis
      using a six-point correction algorithm in the landmark-based method showed 1.24
      mm magnitude of error between images. CONCLUSIONS: Although reliability appears
      to be adequate, the small sample size and high risk of bias among studies make
      available evidence still insufficient to draw strong conclusions.

PMID- 29189040
TI  - Organic Haze as a Biosignature in Anoxic Earth-like Atmospheres.
AB  - Early Earth may have hosted a biologically mediated global organic haze during
      the Archean eon (3.8-2.5 billion years ago). This haze would have significantly
      impacted multiple aspects of our planet, including its potential for habitability
      and its spectral appearance. Here, we model worlds with Archean-like levels of
      carbon dioxide orbiting the ancient Sun and an M4V dwarf (GJ 876) and show that
      organic haze formation requires methane fluxes consistent with estimated Earth
      like biological production rates. On planets with high fluxes of biogenic organic
      sulfur gases (CS2, OCS, CH3SH, and CH3SCH3), photochemistry involving these gases
      can drive haze formation at lower CH4/CO2 ratios than methane photochemistry
      alone. For a planet orbiting the Sun, at 30* the modern organic sulfur gas flux,
      haze forms at a CH4/CO2 ratio 20% lower than at 1* the modern organic sulfur
      flux. For a planet orbiting the M4V star, the impact of organic sulfur gases is
      more pronounced: at 1* the modern Earth organic sulfur flux, a substantial haze
      forms at CH4/CO2 ~ 0.2, but at 30* the organic sulfur flux, the CH4/CO2 ratio
      needed to form haze decreases by a full order of magnitude. Detection of haze at
      an anomalously low CH4/CO2 ratio could suggest the influence of these biogenic
      sulfur gases and therefore imply biological activity on an exoplanet. When these
      organic sulfur gases are not readily detectable in the spectrum of an Earth-like
      exoplanet, the thick organic haze they can help produce creates a very strong
      absorption feature at UV-blue wavelengths detectable in reflected light at a
      spectral resolution as low as 10. In direct imaging, constraining CH4 and CO2
      concentrations will require higher spectral resolution, and R > 170 is needed to
      accurately resolve the structure of the CO2 feature at 1.57 MUm, likely the most
      accessible CO2 feature on an Archean-like exoplanet. Key Words: Organic haze
      Organic sulfur gases-Biosignatures-Archean Earth. Astrobiology 18, 311-329.

PMID- 29189041
TI  - Clinical significance of preoperative liver stiffness measurements in primary HBV
      positive hepatocellular carcinoma.
AB  - AIM: To analyze clinical significance of preoperative liver stiffness measurement
      (LSM) by FibroScan in postcurative resection hepatitis B virus (HBV) related
      hepatocellular carcinoma (HCC). PATIENTS & METHODS: A total of 263 patients
      underwent preoperative LSM and curative operation for primary HBV-positive HCC
      were enrolled. The correlation between preoperative LSM and survival was
      analyzed. RESULTS: All patients were stratified into two groups using the optimal
      cut-off value (13.2 kPa) of LSM using the receiver-operating characteristic.
      Patients with an LSM >=13.2 kPa had poorer overall survival (median, 61.3 vs 48.2
      months, hazard ratio: 0.15; p = 0.009) and recurrence-free survival (median, 60.4
      vs 47.0 months; hazard ratio: 0.32; p = 0.011) than patients with an LSM <13.2
      kPa and LSM also have been confirmed as independent predictor for survival for
      HCC. DISCUSSION: This could potentially guide patient stratification and
      individualized treatment. CONCLUSION: Preoperative LSM can be considered as an
      independent prognostic factor for HBV-positive HCC after curative resection.

PMID- 29189042
TI  - Characterizing indeterminate (Likert-score 3/5) peripheral zone prostate lesions
      with PSA density, PI-RADS scoring and qualitative descriptors on multiparametric
      MRI.
AB  - OBJECTIVE: To determine whether indeterminate (Likert-score 3/5) peripheral zone
      (PZ) multiparametric MRI (mpMRI) studies are classifiable by prostate-specific
      antigen (PSA), PSA density (PSAD), Prostate Imaging Reporting And Data System
      version 2 (PI-RADS_v2) rescoring and morphological MRI features. METHODS: Men
      with maximum Likert-score 3/5 within their PZ were retrospectively selected from
      330 patients who prospectively underwent prostate mpMRI (3 T) without an
      endorectal coil, followed by 20-zone transperineal template prostate mapping
      biopsies +/- focal lesion-targeted biopsy. PSAD was calculated using pre-biopsy
      PSA and MRI-derived volume. Two readers A and B independently assessed included
      men with both Likert-assessment and PI-RADS_v2. Both readers then classified
      mpMRI morphological features in consensus. Men were divided into two groups:
      significant cancer (>= Gleason 3 + 4) or insignificant cancer (<= Gleason 3 +
      3)/no cancer. Comparisons between groups were made separately for PSA & PSAD
      using Mann-Whitney test and morphological descriptors with Fisher's exact test.
      PI-RADS_v2 and Likert-assessment were descriptively compared and percentage inter
      reader agreement calculated. RESULTS: 76 males were eligible for PSA & PSAD
      analyses, 71 for PI-RADS scoring, and 67 for morphological assessment (excluding
      significant image artefacts). Unlike PSA (p = 0.915), PSAD was statistically
      different (p = 0.004) between the significant [median: 0.19 ng ml-2
      (interquartile range: 0.13-0.29)] and non-significant/no cancer [median: 0.13 ng
      ml-2 (interquartile range: 0.10-0.17)] groups. Presence of mpMRI morphological
      features was not significantly different between groups. Subjective Likert
      assessment discriminated patients with significant cancer better than PI-RADS_v2.
      Inter-reader percentage agreement was 83% for subjective Likert-assessment and
      56% for PI-RADS_v2. CONCLUSION: PSAD may categorize presence of significant
      cancer in patients with Likert-scored 3/5 PZ mpMRI findings. Advances in
      knowledge: PSAD may be used in indeterminate PZ mpMRI to guide decisions between
      biopsy vs monitoring.

PMID- 29189043
TI  - An Antarctic Extreme Halophile and Its Polyextremophilic Enzyme: Effects of
      Perchlorate Salts.
AB  - Effects of perchlorate salts prevalent on the surface of Mars are of significant
      interest to astrobiology from the perspective of potential life on the Red
      Planet. Halorubrum lacusprofundi, a cold-adapted halophilic Antarctic archaeon,
      was able to grow anaerobically on 0.04 M concentration of perchlorate. With
      increasing concentrations of perchlorate, growth was inhibited, with half-maximal
      growth rate in ca. 0.3 M NaClO4 and 0.1 M Mg(ClO4)2 under aerobic conditions.
      Magnesium ions were also inhibitory for growth, but at considerably higher
      concentrations, with half-maximal growth rate above 1 M. For a purified
      halophilic beta-galactosidase enzyme of H. lacusprofundi expressed in
      Halobacterium sp. NRC-1, 50% inhibition of catalytic activity was observed at
      0.88 M NaClO4 and 0.13 M Mg(ClO4)2. Magnesium ions were a more potent inhibitor
      of the enzyme than of cell growth. Steady-state kinetic analysis showed that
      Mg(ClO4)2 acts as a mixed inhibitor (KI = 0.04 M), with magnesium alone being a
      competitive inhibitor (KI = 0.3 M) and perchlorate alone acting as a very weak
      noncompetitive inhibitor (KI = 2 M). Based on the estimated concentrations of
      perchlorate salts on the surface of Mars, our results show that neither sodium
      nor magnesium perchlorates would significantly inhibit growth and enzyme activity
      of halophiles. This is the first study of perchlorate effects on a purified
      enzyme. Key Words: Halophilic archaea-Perchlorate-Enzyme inhibition-Magnesium.
      Astrobiology 18, 412-418.

PMID- 29189044
TI  - Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and
      Adolescents with Major Depressive Disorder.
AB  - OBJECTIVES: To evaluate the short-term efficacy and safety of desvenlafaxine (25
      50 mg/d) compared with placebo in children and adolescents with major depressive
      disorder (MDD). METHODS: Outpatient children (7-11 years) and adolescents (12-17
      years) who met DSM-IV-TR criteria for MDD and had screening and baseline
      Children's Depression Rating Scale-Revised (CDRS-R) total scores >40 were
      randomly assigned to 8-week treatment with placebo, desvenlafaxine (25, 35, or 50
      mg/d based on baseline weight), or fluoxetine (20 mg/d). The primary efficacy
      endpoint was change from baseline in CDRS-R total score at week 8, analyzed using
      a mixed-effects model for repeated measures. Secondary efficacy endpoints
      included week 8 Clinical Global Impressions-Severity, Clinical Global Impressions
      Improvement (CGI-I), and response (CGI-I <= 2). Safety assessments included
      adverse events, physical and vital sign measurements, laboratory evaluations,
      electrocardiogram, and the Columbia-Suicide Severity Rating Scale. RESULTS: The
      safety population included 339 patients (children, n = 130; adolescents, n =
      209). The primary endpoint, change from baseline in CDRS-R total score at week 8,
      did not statistically separate from placebo, for either desvenlafaxine (adjusted
      mean [standard error] change, -22.6 [1.17]) or fluoxetine (-24.8 [1.17]; placebo,
      -23.1 [1.18]). Week 8 CGI-I response rates were significantly greater for
      fluoxetine (78.2%; p = 0.017) than for placebo (62.6%); desvenlafaxine (68.7%)
      did not differ from placebo. Other secondary outcomes were consistent with those
      obtained with CDRS-R. Rates of treatment-emergent adverse events were comparable
      among treatment groups (desvenlafaxine, 60.0%; placebo, 70.5%; and fluoxetine,
      64.3%). CONCLUSION: Desvenlafaxine did not demonstrate efficacy for treating MDD
      in children and adolescents in this trial. Because neither desvenlafaxine nor the
      reference medication, fluoxetine, demonstrated a statistically significant
      difference from placebo on the primary endpoint, this was considered a failed
      trial and no efficacy conclusions can be drawn. Desvenlafaxine 25-50 mg/d was
      generally safe and well tolerated in children and adolescents in this study.

PMID- 29189045
TI  - The effects of Baduanjin exercise on fatigue and quality of life in patients with
      heart failure: A randomized controlled trial.
AB  - AIMS: The purpose of this study was to examine the effects of Baduanjin exercise
      on fatigue and quality of life in patients with heart failure. METHODS: The study
      was a randomized controlled trial. Participants diagnosed with heart failure were
      recruited from two large medical centers in northern Taiwan. Participants were
      randomly assigned to the intervention ( n=39) or control ( n=41) groups. Patients
      in the intervention group underwent a 12-week Baduanjin exercise program, which
      included Baduanjin exercise three times per week for 12 weeks at home, a 35
      minute Baduanjin exercise demonstration video, a picture-based educational
      brochure, and a performance record form. The control group received usual care
      and received no intervention. Fatigue and quality of life were assessed using a
      structural questionnaire at baseline, four weeks, eight weeks, and 12 weeks after
      the intervention. RESULTS: Participants in the Baduanjin exercise group showed
      significant improvement in fatigue ( F=5.08, p=0.009) and quality of life (
      F=9.11, p=0.001) over time from baseline to week 12 after the intervention. Those
      in the control group showed significantly worse fatigue ( F=3.46, p=0.033) over
      time from baseline to week 12 and no significant changes in quality of life (
      F=0.70, p=0.518). Compared to the control group, the exercise group demonstrated
      significantly greater improvement in fatigue and quality of life at four weeks,
      eight weeks, and 12 weeks. CONCLUSIONS: This simple traditional exercise is
      recommended for Taiwanese patients with heart failure in order to improve their
      fatigue and quality of life.

PMID- 29189046
TI  - The Feasibility and Potential Impact of Brain Training Games on Cognitive and
      Emotional Functioning in Middle-Aged Adults.
AB  - OBJECTIVES: To investigate whether a commercially available brain training
      program is feasible to use with a middle-aged population and has a potential
      impact on cognition and emotional well-being (proof of concept). METHOD: Fourteen
      participants (ages 46-55) completed two 6-week training conditions using a
      crossover (counterbalanced) design: (1) experimental brain training condition and
      (2) active control "find answers to trivia questions online" condition. A
      comprehensive neurocognitive battery and a self-report measure of depression and
      anxiety were administered at baseline (first time point, before training) and
      after completing each training condition (second time point at 6 weeks, and third
      time point at 12 weeks). Cognitive composite scores were calculated for
      participants at each time point. RESULTS: Study completion and protocol adherence
      demonstrated good feasibility of this brain training protocol in healthy middle
      aged adults. Exploratory analyses suggested that brain training was associated
      with neurocognitive improvements related to executive attention, as well as
      improvements in mood. CONCLUSION: Overall, our findings suggest that brain
      training programs are feasible in middle-aged cohorts. We propose that brain
      training games may be linked to improvements in executive attention and affect by
      promoting cognitive self-efficacy in middle-aged adults.

PMID- 29189047
TI  - Combined serum free light chain levels are associated with carotid
      atherosclerosis in type 2 diabetes mellitus.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus face an increased risk of
      cardiovascular events compared to non-diabetic counterparts. Chronic inflammation
      and activation of the immune system, including B-lymphocyte maturation is
      believed to play a role in atherosclerosis. Recent investigations suggest
      combined serum free light chains as a potential biomarker for cardiovascular
      events. The aim of this analysis was to investigate the association of combined
      serum free light chain with carotid atherosclerosis in subjects with type 2
      diabetes mellitus. METHODS: We performed a cross-sectional analysis of data from
      a prospective single centre 2-year study of 97 patients with type 2 diabetes
      mellitus and insufficiently controlled cardiovascular risk factors. Complete data
      on combined serum free light chain, high-sensitivity C-reactive protein were
      available for 75 subjects. RESULTS: We analysed data of 26 female and 49 male
      subjects, aged 59 +/- 8 years. Their mean body mass index was 31.6 +/- 4.4 kg/m2,
      and the median B-score was 2 (interquartile range: 0-3). Significant positive
      correlations between combined serum free light chain and the B-score ( r = 0.38;
      p = 0.001) as well as combined serum free light chain and high-sensitivity C
      reactive protein ( r = 0.35; p = 0.002) were observed. The adjusted odds ratio
      for a half standard deviation increase in combined serum free light chain was
      1.48 (95% confidence interval: 1.05-2.05) in an ordinal regression model for
      carotid B-score. CONCLUSION: In our study, combined serum free light chain was
      associated with carotid atherosclerosis in subjects with type 2 diabetes
      mellitus.

PMID- 29189048
TI  - Recall of structured radiology reports is significantly superior to that of
      unstructured reports.
AB  - OBJECTIVE: To measure recall of structured compared with unstructured radiology
      reports. METHODS: Institutional review board approval was obtained. Four
      hypothetical radiology reports, two structured and two unstructured reports, were
      created for the purposes of this study by an experienced consultant radiologist.
      The reports, each followed immediately by a multiple-choice questionnaire listing
      possible diagnoses from the report, were distributed to the members of two
      national physician associations using a web-based survey tool. Based on the
      number of correct responses, correct critical findings and incorrect responses,
      rates per number of potential diagnoses were calculated for each individual and
      averaged. The paired sign test compared results between structured and
      unstructured reports. RESULTS: 148 respondents completed the survey, 126 (85.1%)
      of whom were physicians. The mean percentage of incorrect diagnoses was 4.5% for
      structured reports compared with 16.7% for unstructured reports (p < 0.001). The
      average rate of critical diagnosis recall was 82.7% for structured reports and
      65.1% for unstructured reports (p < 0.001). The average percentage of all
      diagnoses detected for structured compared with unstructured reports was 64.3 and
      59.0%, respectively (p = 0.007). CONCLUSION: Recall of structured radiology
      reports is significantly superior to recall of unstructured reports immediately
      after reading the report. Advances in knowledge: A structured radiology report
      format can positively impact the referring clinician's ability to recall the
      critical findings with statistically significance.

PMID- 29189049
TI  - Exploring the impact of professional culture on patient care.

PMID- 29189050
TI  - At home with methicillin-resistant Staphylococcus aureus.

PMID- 29189052
TI  - Pulmonary rehabilitation for people with chronic obstructive pulmonary disease:
      An evidence review.

PMID- 29189051
TI  - Withdrawing or withholding life-sustaining clinically-assisted nutrition and
      hydration.
AB  - The previous article in this law column considered a patient's right to give a
      real consent before a district nurse could proceed with care and treatment. This
      article considers the district nurse's rights and responsibilities when
      considering withdrawing or withholding clinically-assisted nutrition and
      hydration. It focuses on recent cases in the Court of Protection, M v A Hospital
      [2017] , and High Court, NHS Trust v Mr Y & Mrs Y [2017] , and on the need to
      bring such cases to court before treatment is withdrawn.

PMID- 29189053
TI  - Person-centred communication for emotional support in district nursing: SAGE and
      THYME model.
AB  - Patients on district nursing caseloads have multiple physical morbidities, and
      related emotional concerns. District nurses are ideally placed to assess and meet
      patients' emotional needs but in increasingly stretched workplaces, it is
      difficult to find time. There is also evidence that district nurses sometimes
      believe they lack skills to address patients' concerns. Traditional communication
      skills training is useful for encouraging patients to open up about their
      concerns, but less helpful at finding workable solutions. District nurses can be
      afraid to open a 'can of worms' of concerns that they are unable to deal with.
      SAGE and THYME is a person-centred, evidence-based communication skills model
      that addresses district nurses' concerns about time and skills. It provides a
      structure for conversations about concerns, and empowers patients to work with
      district nurses to find solutions. Research suggests that it is a promising model
      for district nursing practice.

PMID- 29189054
TI  - Sparing a thought for the homeless: Using a palliative care lens.

PMID- 29189056
TI  - British Journal of Community Nursing: A year in review.

PMID- 29189055
TI  - Post-cataract eye drops can be avoided by depot steroid injections.
AB  - There are over 400 000 cataract operations now being performed annually in the
      UK. With the majority of those patients being older people, comorbidities such as
      dementia or arthritis can prevent patients putting in their own post-operative
      eye drops. Where there is a lack of family or other support, district nursing
      services are often called upon to administer these eye drops, which are typically
      prescribed four times a day for 4 weeks, thus potentially totalling 112 visits
      for drop instillation per patient. To reduce the burden of these post-operative
      eye drops on district nursing services, administration of an intra-operative sub
      Tenon's depot steroid injection is possible for cataract patients who then do not
      require any post-operative drop instillation. As a trial of this practice, 16
      such patients were injected in one year, thus providing a reduction of 1792 in
      the number of visits requested. Taking an estimated cost of each district nurse
      visit of L38, this shift in practice potentially saved more than L68 000; the
      additional cost of the injection over the cost of eye drops was just L8.80 for
      the year. This practice presents an opportunity to protect valuable community
      nursing resources, but advocacy for change in practice would be needed with
      secondary care, or via commissioners.

PMID- 29189057
TI  - Experience of emotion in frail older people towards the end of life: A secondary
      data analysis.
AB  - People are living longer, but with increased age comes greater frailty and multi
      morbidity. This secondary data analysis examines transcripts from interviews with
      11 frail older people and 6 informal carers to explore emotion in relation to
      frailty and deteriorating health. Anger and frustration were frequently
      experienced with declining functional ability; sadness occurred with social
      isolation, loss of autonomy and independence; anxiety was evident when transition
      to a care home was discussed; and contentment was described when connecting with
      others. Reluctant acceptance emerged as a coping strategy. Insights gained from
      analysing emotion may inform communications training courses for community
      nurses, though further research is required.

PMID- 29189058
TI  - The state of care in a community setting.

PMID- 29189060
TI  - Medicines management in community settings: The role of the nurse.

PMID- 29189059
TI  - Pilot evaluation of the management of chronic oedema in community settings
      project.
AB  - AIMS: The aim of this economic analysis was to estimate the economic impact of
      the On the Ground Education Programme (OGEP) within one local University Health
      Board (UHB) in Wales. BACKGROUND: The burden of managing chronic oedema can be
      considerable to the NHS. Developing innovative solutions to the care and
      management of patients with chronic oedema has the potential to deliver prudent,
      cost-effective and high quality care within NHS Wales. DESIGN: The study was a
      pilot Evaluation of the OGEP using retrospectively and prospectively collected
      patient recalled data. METHODS: A questionnaire collected health care service use
      data prior to receiving the OGEP (baseline) and at 3 months follow-up from 97
      patients during the period June 2016 and January 2017. In addition, we analysed a
      patient reported health outcome using the EQ-5D 5L, which was completed by
      patients at the same two assessment points. RESULTS/FINDINGS: The total cost of
      managing chronic oedema in the 97 patients recruited was L563 729 (mean patient
      cost L5812 SD (L5870) at baseline and L445 098 (including the addition of
      intervention costs) (mean patient cost L4589 (SD L5465) at 3 months follow-up.
      Improvements in the EQ-5D 5L score increasing from 0.40 (SD 0.25) at baseline to
      0.54 (SD 0.23) at 3 months follow-up. CONCLUSIONS: Our research show health care
      resource use and costs decreased, while health-related quality of life scores
      increased.

PMID- 29189061
TI  - The Usefulness of SP174 Anti-RASQ61R Immunohistochemistry in Melanoma, Thyroid,
      and Colorectal Cancers.

PMID- 29189062
TI  - Factor V Inhibitors: A Diagnostic and Therapeutic Challenge.
AB  - Historically, inhibitors to coagulation factor V (FV) most often have developed
      in patients treated with bovine thrombin, a topical hemostatic agent used during
      surgical procedures. With the advent of newer hemostatic agents, and the
      concurrent diminished use of bovine thrombin, the incidence of FV inhibitors has
      fallen. Nevertheless, FV inhibitors are occasionally seen on an idiopathic basis
      as well as in association with medications, malignancies, autoimmune disorders,
      pregnancy, and infections. Factor V inhibitors may present with life-threatening
      bleeding or thrombosis, or they may be discovered incidentally as a coagulation
      screening test abnormality. Management of patients with FV inhibitors is
      challenging and consists of control of bleeding and eradication of the inhibitor.
      In this short overview we review the role of platelet and plasma FV in hemostasis
      and discuss the unique characteristics, clinical features, diagnosis, treatment,
      and prognosis associated with FV inhibitors.

PMID- 29189063
TI  - Classification, Morphology, Molecular Pathogenesis, and Outcome of Premalignant
      Lesions of the Pancreas.
AB  - CONTEXT: - Invasive pancreatic ductal adenocarcinoma has a greater than 90%
      mortality rate at 5 years. Understanding noninvasive, curable precursor lesions
      gives us the best hope for reducing mortality from pancreatic ductal
      adenocarcinoma. The 3 pancreatic precursor lesions that have been well studied
      include intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and
      pancreatic intraepithelial neoplasia. OBJECTIVE: - To give an update on the
      latest clinical, molecular, and pathologic advances in intraductal papillary
      mucinous neoplasm, mucinous cystic neoplasm, and pancreatic intraepithelial
      neoplasia for the general surgical pathologist. DATA SOURCES: - The current
      literature was analyzed and the authors' experiences with institutional and
      consult material were incorporated. CONCLUSIONS: - Our understanding of the
      molecular alterations that lead from pancreatic precursor lesion to invasive
      carcinoma continues to evolve. These advances aid clinicians in their treatment
      decisions and researchers in their search for actionable, druggable targets.

PMID- 29189064
TI  - The Updated World Health Organization Glioma Classification: Cellular and
      Molecular Origins of Adult Infiltrating Gliomas.
AB  - CONTEXT: - In the recently updated World Health Organization (WHO) classification
      of central nervous system tumors, our concept of infiltrating gliomas as a
      molecular dichotomy between oligodendroglial and astrocytic tumors has been
      codified. Advances in animal models of glioma and a wealth of sophisticated
      molecular analyses of human glioma tissue have led to a greater understanding of
      some of the biologic underpinnings of gliomagenesis. OBJECTIVE: - To review our
      understanding of gliomagenesis in the setting of the recently updated WHO
      classification of central nervous system tumors. Topics addressed include a
      summary of an updated diagnostic schema for infiltrating gliomas, the crucial
      importance of isocitrate dehydrogenase mutations, candidate cells of origin for
      gliomas, environmental and other posited contributing factors to gliomagenesis,
      and the possible role of chromatin topology in setting the stage for
      gliomagenesis. DATA SOURCES: - We conducted a primary literature search using
      PubMed. CONCLUSIONS: - With multidimensional molecular data sets spanning
      increasingly larger numbers of patients with infiltrating gliomas, our
      understanding of the disease at the point of surgical resection has improved
      dramatically and this understanding is reflected in the updated WHO
      classification. Animal models have demonstrated a diversity of candidates for
      glioma cells of origin, but crucial questions remain, including the role of
      neural stem cells, more differentiated progenitor cells, and glioma stem cells.
      At this stage the increase in data generated from human samples will hopefully
      inform the creation of newer animal models that will recapitulate more accurately
      the diversity of gliomas and provide novel insights into the biologic mechanisms
      underlying tumor initiation and progression.

PMID- 29189065
TI  - Focusing on Preinvasive Neoplasia: A Molecular Frontier at the Pathologist's
      Fingertips.

PMID- 29189066
TI  - Path to the Future: Join Hands With Your Fellow Pathologists-Make Your Community
      Stronger.

PMID- 29189067
TI  - Assessing the value of practice-based leg ulcer education to inform
      recommendations for change in practice.
AB  - The purpose of this paper is to assess the value of accredited leg ulcer
      education in influencing changes in practice. This is a before and after
      educational evaluation that adopted a qualitative survey approach of 12 primary
      care nurses attending the Nurse-Led Assessment and Management of Leg Ulcers
      accredited CPD module at a London university. The findings revealed that 6 out of
      the 8 nurses who completed the final interviews were satisfied that all learning
      outcomes for the module had been met. All of the nurses commented they had
      changed at least one aspect of practice following the module with the majority
      stating a number of improvements had been made relating to improved knowledge,
      practical skills, treatment and patient concordance. The evaluation was limited
      to a small cohort of primary care nurses and further longitudinal research is
      required to investigate the effectiveness across multiple cohorts.

PMID- 29189068
TI  - New standards of proficiency for registered nurses.

PMID- 29189069
TI  - The impact of an educational intervention on home support workers' ability to
      detect early pressure ulcer damage.
AB  - OBJECTIVE: To investigate the impact of an educational intervention on home
      support workers' ability to detect early pressure ulcer damage. METHOD: A
      repeated measure design was employed to quantify the effectiveness of an
      educational intervention, consisting of one pre-test and two post-tests. RESULTS:
      Education was provided to home support workers and this was followed by an
      assessment of their ability to correctly classify 20 photographs detailing
      varying stages of skin damage severity. At the baseline (pre-education), 58% of
      the photographs were classified correctly. At post-test 1, 55% of the photographs
      were classified correctly. In post-test 2 this increased to 58%, achieving the
      original baseline scores. There was a moderate negative relationship between pre
      training and post-test 2 scores (r=-0.44; n=27; p=0.02). CONCLUSIONS: The
      educational intervention has been shown not to have a statistically significantly
      positive effect on home support workers' ability to detect early pressure ulcer
      damage. The moderate negative relationship between pre-training and post-test 2
      scores concur with the aforementioned qualitative findings, and similarly
      indicate behaviour associated with individuals experiencing difficulty
      comprehending new health terms.

PMID- 29189070
TI  - A closer look at the wound infection continuum.

PMID- 29189071
TI  - Obtaining the optimum moist wound healing environment.

PMID- 29189073
TI  - Sharing knowledge in pursuit of best practice.

PMID- 29189072
TI  - Woundcare4Heroes: 2017 annual conference.

PMID- 29189074
TI  - The social and physical benefits of the Lindsay Leg Clubs.

PMID- 29189075
TI  - Early wound infection identification using the WIRE tool in community health care
      settings: An audit report.
AB  - Wound infection is proving to be a challenge for health care professionals. The
      associated complications and cost of wound infection is immense and can lead to
      death in extreme cases. Current management of wound infection is largely
      subjective and relies on the knowledge of the health care professional to
      identify and initiate treatment. In response, we have developed an infection
      prediction and assessment tool. The Wound Infection Risk-Assessment and
      Evaluation tool (WIRE) and its management strategy is a tool with the aim to
      bring objectivity to infection prediction, assessment and management. A local
      audit carried out indicated a high infection prediction rate. More work is being
      done to improve its effectiveness.

PMID- 29189076
TI  - Extremit-Ease compression garment: A review and cases.
AB  - The rates of chronic oedema in the US continue to grow from multiple causative
      factors. One such factor is the skyrocketing rates of morbid obesity. There are
      about 40 million obese people in the US today. Among those people, the prevalence
      rate of lymphoedema is 74% ( Fife and Carter, 2008 ). Treatment usually involves
      some type of compression for life, but that is easier said than done. Many
      patients with chronic oedema have dexterity issues or have limited abilities to
      put on tight compression options. This article explores a product that has just
      been recently launched on the market: the Extremit-Ease(r) compression garment.
      This article also looks at five case studies involving the product to evaluate
      its effectiveness in the treatment of this growing condition. We explore the
      increasing problem of chronic oedema, specifically oedema caused by lymphoedema
      and venous stasis, and how Extremit-Ease compression garments could assist
      patient compliance with the gold standard treatment.

PMID- 29189077
TI  - The importance of team working in wound management.

PMID- 29189078
TI  - Use of metal/metal oxide spherical cluster and hydroxyl metal coordination
      complex for descriptor calculation in development of nanoparticle cytotoxicity
      classification model.
AB  - Computational approaches have been suggested as an informative tool for risk
      assessment of nanomaterials. Nano (quantitative) structure-activity relationship,
      nano-(Q)SAR, models have been developed to predict toxicity of metal oxide (MOx)
      nanoparticles (NPs); however, the packing structure and cluster of nanoparticle
      have been included for the descriptor calculation in only two studies. This study
      proposed spherical cluster and hydroxyl metal coordination complex to calculate
      descriptors for development of nanoparticle cytotoxicity classification model.
      The model cluster was generated from metal (M) or MOx crystal structure to
      calculate physicochemical properties of M/MOx NPs and the hydroxyl metal
      coordination complex was used to calculate the properties of the metal cation in
      an aqueous environment. Data were collected for 2 M and 19 MOx NPs in human
      bronchial epithelial cell lines and murine myeloid cell lines at 100 MUg/ml after
      24 hours exposure. The model was developed with scaled HOMO energy of the model
      cluster and polarizability of the hydroxyl metal coordination complex, as
      reactivity of the particles and the cations explained cause of cytotoxic action
      by M/MOx NPs. As the developed model achieved 90.31% accuracy, the classification
      model in this work can be used for virtual screening of toxic action of M/MOx
      NPs.

PMID- 29189079
TI  - Triterpenoid saponins from the buds of Lonicera similis.
AB  - Four new lupane triterpenoid saponins, along with one known lupane and eight
      hederagenin saponins, were isolated from the EtOH extract of the buds of Lonicera
      similis Hemsl. The structures of the new compounds were established as 3-O-beta-D
      glucopyranosyl-(1->2)-beta-D-glucopyranosyl 23-hydroxybetulinic acid 28-O-beta-D
      glucopyranosyl ester (lonisimilioside A, 1), 3-O-beta-D-glucopyranosyl-(1->2)
      beta-D-glucopyranosyl 23-hydroxybetulinic acid 28-O-beta-D-glucopyranosyl-(1->6)
      beta-D-glucopyranosyl ester (lonisimilioside B, 2), 3-O-beta-D-glucopyranosyl-(1
      >2)-beta-D-glucopyranosyl betulinic acid 28-O-beta-D-glucopyranosyl-(1->6)-beta-D
      glucopyranosyl ester (lonisimilioside C, 3) and 3-O-beta-D-glucopyranosyl-(1->2)
      beta-D-glucopyranosyl-(1->6)-beta-D-glucopyranosyl betulinic acid 28-O-beta-D
      glucopyranosyl ester (lonisimilioside D, 4), respectively. The cytotoxic
      activities of the isolates against human cancer cell lines HepG2, MCF-7 and A-549
      were evaluated. Only the monodesmosidic saponin with a free carboxyl group at C
      28 (12) exhibited significant cytotoxicities against HepG2, MCF-7 and A-549 cell
      lines with the IC50 values of 8.98 +/- 0.19, 12.48 +/- 0.45 and 11.62 +/- 0.54
      MUM, respectively. Furthermore, Hoechst fluorescence 33342 staining was used to
      demonstrate that 12 could induce HepG2 and A-549 cells apoptosis significantly.

PMID- 29189082
TI  - The value of time in therapeutic range in the prediction of outcomes at a
      populational level in patients treated with vitamin K antagonists.

PMID- 29189081
TI  - Propulsion of blood through the right heart circulatory system.
AB  - Venous return, the right heart function and the pulmonary circulation is an
      integrated functional unit. The right ventricle is particularly load sensitive,
      and will be influenced directly by the venous and pulmonary physiology. In this
      paper we present important physiological principles that govern the diagnosis and
      treatment of dysfunctions affecting the return of blood to the heart and the
      transfer of the cardiac output from the right to the left side. We do evaluate
      both basic science and the clinical literature pointing to practical aspects of
      physiological knowledge.

PMID- 29189083
TI  - Effectiveness of physiotherapy in elderly patients with dementia: a prospective,
      comparative analysis.
AB  - BACKGROUND: The aim of this study was to assess the efficacy of physiotherapy in
      nursing home patients with comorbid dementia. MATERIALS AND METHODS: The study
      group consisted of 88 patients, including 48 people with dementia and 40 people
      without dementia. Before and after physiotherapy, the Mini Mental State
      Examination and Barthel Index were used. RESULTS: Elderly patients without
      dementia achieved a greater improvement in functional status. The level of
      cognitive functioning at the time of admission to a nursing home, but not the
      patient's functional status, had a significant impact on physiotherapy efficacy.
      CONCLUSION: Understanding the role of dementia in the rehabilitation process is
      important for care planning. More research is required to ascertain the efficacy
      of physiotherapy in people with moderate to severe dementia, including the best
      strategies to improve their functional status. Implications for Rehabilitation
      The level of cognitive function is important in the rehabilitation process, and
      it influences effectiveness of physiotherapy. Physiotherapy efficacy in the group
      of patients with coexisting dementia is lower than that in patients without
      dementia. Regular physiotherapy can also improve functional status in patients
      with coexisting dementia. The results of the study may have utilitarian
      implications, leading to a change in therapy regimens at physiotherapy centres
      treating disabled chronically ill people with coexisting dementia.

PMID- 29189084
TI  - Depressive symptoms and their risk factors in midlife women in the Middle East: a
      systematic review.
AB  - INTRODUCTION: Women may experience different menopausal symptoms across different
      cultures around the world. The purpose of this study was to determine the
      prevalence and contributing factors of depression in midlife women in the Middle
      East. METHODS: Electronic databases including PubMed, Medline, PsycINFO, CINAHL,
      Web of Science, SCOPUS, and Google scholar were searched. The quality of articles
      was assessed by using the risk of bias tool. RESULTS: Sixteen articles were used
      for this review. The prevalence for depressive symptoms in perimenopausal women
      is higher than in premenopausal women. The overall data also suggest that
      depressive symptoms may be more prevalent in postmenopausal women than in
      premenopausal women. Studies reported sociodemographic, physical, psychological,
      cultural and sexual risk factors for depressive symptoms in middle-aged women.
      Risk of bias for a majority of the studies conducted in the Middle Eastern region
      on depression in midlife was moderate. CONCLUSION: Consistent with other areas in
      the world, midlife women in the Middle East region are at higher risk for
      depression due to the presence of different factors. High-quality longitudinal
      studies of representative samples, using validated questionnaires, are needed to
      provide more accurate prevalence data and the association between menopause and
      menopausal symptoms in women in the Middle East.

PMID- 29189085
TI  - Sharing End-of-Life Care Preferences with Family Members: Who Has the Discussion
      and Who Does Not.
AB  - BACKGROUND: Research suggests that greater engagement in family discussions
      concerning end-of-life (EOL) care preferences could improve advance care planning
      and EOL outcomes. However, a substantial number of people have not had such
      discussions. OBJECTIVE: The study's objective was to understand attitudes and
      experiences influencing engagement in discussions of EOL care preferences with
      family members, including the role of healthcare providers in such discussions.
      METHODS: We conducted focus group interviews with 36 non-Hispanic White, African
      American, and Hispanic community-dwelling participants. Participants were divided
      among groups to explore differences between those who had or had not engaged in
      EOL care discussions. Atlas.ti version 7 was used to analyze data employing an
      open-coding method. RESULTS: Participants' mean age was 70 (range: 58-87); three
      fourths were female (n = 27). Twenty were white, non-Hispanic; 10 were African
      American; and 6 were Hispanic. Four themes emerged from the data, (1) being
      proactive or passive/reactive; (2) perceiving discussion of death as normal or
      abnormal; (3) response to family resistance/disconnection; and (4) knowledge
      acquired. A fifth theme, the role of healthcare providers in family EOL care
      discussions, resulted from facilitators' questions. Theme examination led to
      identification of a central category, decision-making. CONCLUSIONS: It is
      important to understand the differing experiences and attitudes of those who do
      or do not engage in EOL discussions. Research is needed on healthcare
      practitioners' use of decision-making tools to help patients discuss their EOL
      care preferences with family and others, the goal of which is to provide care
      consistent with patients' goals.

PMID- 29189086
TI  - Case series of diagnostic shift from bipolar disorder to schizoaffective
      disorder.
AB  - OBJECTIVE: To describe three cases of diagnostic shift from bipolar I disorder
      (BD) to schizoaffective disorder (SAD). METHODS: BD patients were clinically
      assessed and followed up in a mood disorder program. A questionnaire was applied
      to assess clinical and socio-demographic characteristics, and a Structured
      Clinical Interview (SCID-I) was conducted. RESULTS: We identified three patients
      with diagnosis conversion to SAD from 2005 to 2016. The mean time between BD
      diagnosis and the diagnostic shift to SAD was 9 years. CONCLUSIONS: Psychotic
      symptoms may become persistent, chronic and unrelated to the presence of mood
      episodes many years after the beginning of BD. Psychiatrists should be aware of
      this and reassess the diagnosis during the longitudinal course of BD, especially
      in those patients who present psychotic symptoms.

PMID- 29189087
TI  - Diagnostic usefulness of the QuantiFERON-TB gold in-tube test (QFT-GIT) for
      tuberculous vertebral osteomyelitis.
AB  - BACKGROUND: Interferon (IFN)-gamma-releasing assay for diagnosing tuberculosis
      (TB) has shown promise; however, there are only a few reports on usefulness of
      the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral
      osteomyelitis. METHODS: All patients presenting at a tertiary hospital between
      January 2010 and July 2016 with suspected TB vertebral osteomyelitis were
      retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We
      used QFT-GIT to measure the IFN-gamma response to ESAT-6, CFP-10 and TB7.7.
      RESULTS: A total of 141 patients were enrolled; 32 (23%) were categorized as
      having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as
      not TB. Of these, 16 patients with probable and possible TB were excluded from
      the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli
      stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis
      were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients,
      respectively, among the 32 patients with confirmed TB. The overall sensitivity,
      specificity, positive predictive value, negative predictive value, likelihood
      ratio for a positive result, and likelihood ratio for a negative result of the
      QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75
      98%), 65% (95% CI, 54-75%), 50% (95% CI, 42-58%), 95% (95% CI, 86-98%), 2.59 (95%
      CI, 1.89-3.55) and 0.14 (95% CI, 0.05-0.43), respectively. CONCLUSION: The QFT
      GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis
      because the negative test results may be useful for excluding a diagnosis of
      active TB vertebral osteomyelitis.

PMID- 29189088
TI  - Intra- and interpersonal effects of coping on the psychological well-being of
      adults with sensory loss and their spouses.
AB  - PURPOSE: The aim of the current study was to examine the associations between
      coping and psychological well-being among adults with sensory loss and their
      spouses. METHODS: A total of 183 adults with sensory loss and 133 spouses
      participated in an online survey and were followed up six months later. Coping
      and well-being were measured using the Brief Coping Orientation to Problems
      Experienced Scale (Brief COPE) and the five-item World Health Organization Well
      Being Index (WHO-5), respectively. Cross-sectional and longitudinal intra- and
      interpersonal effects of coping on psychological well-being were analyzed using a
      structural equation modeling approach. RESULTS: Results showed that a significant
      portion of adults with sensory loss (32.4%) and spouses (23.8%) had poor well
      being, and this remained stable over the six-month period. Coping styles
      associated with the well-being of adults with sensory loss included active
      coping, avoidance, distraction, venting and spouse support seeking. Coping styles
      associated with the well-being of spouses included support seeking, distraction,
      venting, avoidance (by partner) and humor (by partner). CONCLUSION: The results
      highlight the need to support the well-being of adults with sensory loss and
      their spouses in rehabilitation, and the importance of both intra- and
      interpersonal coping in the adjustment process. Implications for rehabilitation
      Rehabilitation specialists and social workers working with adults with sensory
      loss should, where possible, incorporate family members into support plans.
      Rehabilitation specialists and social workers working in sensory rehabilitation
      should be mindful of how the coping styles of one partner can impact the well
      being of their significant other. In addition to promoting positive coping
      behaviors, such as planning and support seeking, rehabilitation specialists and
      social workers should also take care to identify and reduce maladaptive coping
      behaviors such as avoidance and distraction. Online and print information for
      spouses on how to cope with a partner's sensory loss should be available and
      accessible for couples attending sensory rehabilitation clinics.

PMID- 29189090
TI  - Characterization of Whooper Swan (Cygnus cygnus) Interferon alpha: Prokaryotic
      Expression, Biological Activities, and Physicochemical Characteristics.
AB  - Whooper swan Cygnus cygnus interferon alpha (CyIFN-alpha) gene was amplified from
      genomic DNA in the liver of whooper swan, which encodes a 192-amino acid protein
      containing a 29-amino acid signal peptide. Bioinformatics analysis showed it
      containes 7 cysteine residues and 5 alpha helices. After expression in
      prokaryote, purification and renaturation, CyIFN-alpha was analyzed on its
      physicochemical property and antiviral activity. In chicken embryo fibroblasts,
      CyIFN-alpha exerted more superior anti-vesicular stomatitis virus (VSV), avian
      influenza virus (AIV), and Newcastle disease virus (NDV) activity than chicken
      IFN-alpha, an effective therapeutic agent used for viral infections clinically.
      Contrarily, these antiviral activities were abrogated by rabbit anti-CyIFN-alpha
      in vitro. Moreover, CyIFN-alpha was shown to be highly sensitive to trypsin,
      however, it remained stable despite changes in pH and temperature. In addition,
      CyIFN-alpha induced the transcription of Mx1, ISG12, and IFIT5 (ISG58) genes, as
      well as the expression of Mx1 protein, in a time-dependent manner. In conclusion,
      we first cloned and expressed CyIFN-alpha and tested its biological activity in
      vitro. Our findings facilitate further research on the role of type I IFN in
      antiviral defense responses in whooper swan and other Natatores.

PMID- 29189089
TI  - Interferon-inducible Mx1 protein is highly expressed in renal tissues from
      treatment-naive lupus nephritis, but not in those under immunosuppressive
      treatment.
AB  - OBJECTIVES: The aim of this study was to clarify the consequences of Mx1, one of
      the IFN-inducible proteins, in the peripheral blood as well as in renal tissues
      in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Mx1
      protein concentrations in (PBMCs) from 18 SLE patients mostly in their stable
      disease status, 11 IgA nephropathy (IgAN) patients, 5 ANCA-associated vasculitis
      (AAV) patients and 16 healthy controls were measured using enzyme-linked
      immunosorbent assay (ELISA). Mx1 expression in renal specimens from 18 patients
      with lupus nephritis (LN), 18 with IgAN and 10 with AAV were evaluated using
      immunohistochemistry. RESULTS: Mx1 protein concentrations in lysates of PBMCs
      were significantly higher in SLE patients compared with those in other three
      groups. Mx1-positive area in renal tissues was significantly dominant in both
      glomeruli and renal tubules of LN compared with other renal diseases. Renal Mx1
      protein levels were lower in LN after immunosuppressive treatment, compared with
      those from immunosuppressant-naive patients. CONCLUSION: Mx1 levels were
      upregulated in lupus peripheral blood even when their disease activities were
      stable. On the other hand, Mx1 was highly expressed in kidneys from patients with
      LN before treatment, which was decreased after immunosuppressive treatment. These
      results suggest that Mx1 is a potential marker for the diagnosis of SLE in the
      peripheral blood and also for the activity of lupus nephritis in the kidney.

PMID- 29189091
TI  - DNR: "Do Not Resuscitate" or "Death Not Reversible"?
AB  - Allowing physicians to write a do not resuscitate (DNR) or do not administer
      cardiopulmonary resuscitation order after properly informing patients and their
      families that death would be irreversible offers a more rational and
      compassionate approach than traditional shared decision making in establishing a
      DNR status for some hospitalized patients.

PMID- 29189092
TI  - Serial semi-quantitative measurement of fecal calprotectin in patients with
      ulcerative colitis in remission.
AB  - BACKGROUND: Fecal calprotectin (FC) correlates with clinical and endoscopic
      activity in ulcerative colitis (UC), and it is a good predictor of relapse.
      However, its use in clinical practice is constrained by the need for the patient
      to deliver stool samples, and for their handling and processing in the
      laboratory. The availability of hand held devices might spread the use of FC in
      clinical practice. OBJECTIVES: To evaluate the usefulness of a rapid semi
      quantitative test of FC in predicting relapse in patients with UC in remission.
      MATERIALS AND METHODS: Prospective, multicenter study that included UC patients
      in clinical remission for >=6 months on maintenance treatment with mesalamine.
      Patients were evaluated clinically and semi-quantitative FC was measured using a
      monoclonal immunochromatography rapid test at baseline and every three months
      until relapse or 12 months of follow-up. RESULTS: One hundred and ninety-one
      patients had at least one determination of FC. At the end of follow-up, 33
      patients (17%) experienced clinical relapse. Endoscopic activity at baseline (p =
      .043) and having had at least one FC > 60 MUg/g during the study period (p = .03)
      were associated with a higher risk of relapse during follow-up. We obtained a
      total of 636 semi-quantitative FC determinations matched with a three-month
      follow-up clinical assessment. Having undetectable FC was inversely associated
      with early relapse (within three months), with a negative predictive value of
      98.6% and a sensitivity of 93.9%. CONCLUSIONS: Serial, rapid semi-quantitative
      measurement of FC may be a useful, easy and cheap monitoring tool for patients
      with UC in remission.

PMID- 29189093
TI  - A Palliative Radiation Oncology Consult Service's Impact on Care of Advanced
      Cancer Patients.
AB  - INTRODUCTION: Palliative radiation therapy (PRT) is a commonly utilized
      intervention for symptom palliation among patients with metastatic cancer, yet it
      is under-recognized as a distinct area of subspecialty within radiation oncology.
      OBJECTIVE: We developed a multidisciplinary service model within radiation
      oncology called the Palliative Radiation Oncology Consult (PROC) service to
      improve the quality of cancer care for advanced cancer patients. We assessed the
      service's impact on patient-related and healthcare utilization outcomes. DESIGN:
      Patients were included in this observational cohort study if they received PRT at
      a single tertiary care hospital between 2009 and 2017. We compared outcomes of
      patients treated after (post-intervention group) to those treated before (control
      group) PROC's establishment using unadjusted and propensity score adjusted
      analyses. RESULTS: Of the 450 patients in the cohort, 154 receive PRT pre- and
      296 after PROC's establishment. In comparison to patients treated pre-PROC, post
      PROC patients were more likely to undergo single-fraction radiation (RR: 7.74,
      95% CI: 3.84-15.57) and hypofraction (2-5 fraction) radiation (RR: 10.74, 95% CI:
      5.82-19.83), require shorter hospital stays (21 vs. 26.5 median days, p = 0.01),
      and receive more timely specialty-level palliative care (OR: 2.65, 95% CI: 1.56
      4.49). Despite shortened treatments, symptom relief was similar (OR: 1.35, 95%
      CI: 0.80-2.28). CONCLUSION: The PROC service was associated with more efficient
      radiation courses, substantially reduced hospital length of stays, and more
      timely palliative care consultation, without compromising symptom improvements.
      These results suggest that a multidisciplinary care delivery model can lead to
      enhanced quality of care for advanced cancer patients.

PMID- 29189094
TI  - FijiWingsPolarity: An open source toolkit for semi-automated detection of cell
      polarity.
AB  - Epithelial cells are defined by apical-basal and planar cell polarity (PCP)
      signaling, the latter of which establishes an orthogonal plane of polarity in the
      epithelial sheet. PCP signaling is required for normal cell migration,
      differentiation, stem cell generation and tissue repair, and defects in PCP have
      been associated with developmental abnormalities, neuropathologies and cancers.
      While the molecular mechanism of PCP is incompletely understood, the deepest
      insights have come from Drosophila, where PCP is manifest in hairs and bristles
      across the adult cuticle and organization of the ommatidia in the eye. Fly wing
      cells are marked by actin-rich trichome structures produced at the distal edge of
      each cell in the developing wing epithelium and in a mature wing the trichomes
      orient collectively in the distal direction. Genetic screens have identified key
      PCP signaling pathway components that disrupt trichome orientation, which has
      been measured manually in a tedious and error prone process. Here we describe a
      set of image processing and pattern-recognition macros that can quantify trichome
      arrangements in micrographs and mark these directly by color, arrow or colored
      arrow to indicate trichome location, length and orientation. Nearest neighbor
      calculations are made to exploit local differences in orientation to better and
      more reliably detect and highlight local defects in trichome polarity. We
      demonstrate the use of these tools on trichomes in adult wing preps and on actin
      rich developing trichomes in pupal wing epithelia stained with phalloidin.
      FijiWingsPolarity is freely available and will be of interest to a broad
      community of fly geneticists studying the effect of gene function on PCP.

PMID- 29189096
TI  - Regulation and functions of RhoU and RhoV.
AB  - Rho GTPases play central roles in a wide variety of cellular processes, including
      cytoskeletal dynamics, cell adhesion and cell polarity. RhoU and RhoV are Rho
      GTPases that have some atypical properties compared with classical Rho family
      members, such as the presence of N- and C-terminal extension regions, unusual
      GDP/GTP cycling and post-translational modification by palmitoylation but not
      prenylation. Their activity and localization is regulated by the N-terminal and C
      terminal regions, and so far no GEFs or GAPs have been identified for them.
      Similar to Rac and Cdc42, they interact with PAK serine/threonine kinases, and in
      the case of PAK4, this interaction leads to RhoU protein stabilization. In cells,
      RhoU and RhoV alter cell shape and cell adhesion, which probably underlies some
      of the phenotypes reported for these proteins in vivo, for example in heart
      development and epithelial morphogenesis. However, the molecular basis for these
      functions of RhoU and RhoV remains to be characterized.

PMID- 29189095
TI  - Pregnancy history, coronary artery calcification and bone mineral density in
      menopausal women.
AB  - OBJECTIVE: This study examined relationships, by pregnancy histories, between
      bone mineral density (BMD) and coronary artery calcification (CAC) in
      postmenopausal women. METHODS: Forty women identified from their medical record
      as having pre-eclampsia (PE) were age/parity-matched with 40 women having a
      normotensive pregnancy (NP). Vertebral (T4-9) BMD and CAC were assessed by
      quantitative computed tomography in 73 (37 with PE and 36 with NP) of the 80
      women. Analyses included linear regression using generalized estimating
      equations. RESULTS: Women averaged 59 years of age and 35 years from the index
      pregnancy. There were no significant differences in cortical, trabecular or
      central BMD between groups. CAC was significantly greater in the PE group (p =
      0.026). In multivariable analysis, CAC was positively associated with cortical
      BMD (p = 0.001) and negatively associated with central BMD (p = 0.036). There was
      a borderline difference in the association between CAC and central BMD by
      pregnancy history (interaction, p = 0.057). CONCLUSIONS: Although CAC was greater
      in women with a history of PE, vertebral BMD did not differ between groups.
      However, both cortical and central BMD were associated with CAC. The central BMD
      association was marginally different by pregnancy history, suggesting perhaps
      differences in underlying mechanisms of soft tissue calcification.

PMID- 29189097
TI  - A Fungus-Inducible Pepper Carboxylesterase Exhibits Antifungal Activity by
      Decomposing the Outer Layer of Fungal Cell Walls.
AB  - Colletotrichum species are major fungal pathogens that cause devastating
      anthracnose diseases in many economically important crops. In this study, we
      observed the hydrolyzing activity of a fungus-inducible pepper carboxylesterase
      (PepEST) on cell walls of C. gloeosporioides, causing growth retardation of the
      fungus by blocking appressorium formation. To determine the cellular basis for
      the growth inhibition, we observed the localization of PepEST on the fungus and
      found the attachment of the protein on surfaces of conidia and germination tubes.
      Moreover, we examined the decomposition of cell-wall materials from the fungal
      surface after reaction with PepEST, which led to the identification of 1,2
      dithiane-4,5-diol (DTD) by gas chromatography mass spectrometry analysis.
      Exogenous DTD treatment did not elicit expression of defense-related genes in the
      host plant but did trigger the necrosis of C. gloeosporioides. Furthermore, the
      DTD compound displayed protective effects on pepper fruits and plants against C.
      gloeosporioides and C. coccodes, respectively. In addition, DTD was also
      effective in preventing other diseases, such as rice blast, tomato late blight,
      and wheat leaf rust. Therefore, our results provide evidence that PepEST is
      involved in hydrolysis of the outmost layer of the fungal cell walls and that DTD
      has antifungal activity, suggesting an alternative strategy to control
      agronomically important phytopathogens.

PMID- 29189098
TI  - The effects of ovarian hormones on stressor-induced hormonal responses,
      glucocorticoid receptor expression and translocation, and genes related to
      receptor signaling in adult female rats.
AB  - Estradiol potentiates hypothalamic-pituitary-adrenal activity and delays the
      return of glucocorticoid secretion to baseline after a stressor exposure in
      female rats; we investigated whether estradiol effects involve actions on
      glucocorticoid receptor (GR) translocation and expression of receptor co
      chaperones. In Experiment 1 intact females and ovariectomized (OVX) females were
      treated for four days with vehicle (VEH), 17beta-estradiol benzoate (EB), or EB
      and progesterone (EB + P). Samples were taken from rats in the home cage
      (baseline) or after 30 min of restraint stress in a plastic restrainer (post
      restraint) (n = 10/group). OVX-VEH treatment reduced baseline and post-restraint
      plasma concentrations of corticosterone versus all other treatments. Western
      blots indicated that OVX-VEH treated rats had greater hippocampal cytosolic GR
      expression than other treatments. Stress increased hippocampal nuclear GR
      expression, but without treatment differences. In Experiment 2 OVX rats were
      treated daily with VEH, EB, or EB + P (n = 8/group). OVX-VEH rats showed a lower
      stimulation of corticosterone secretion by restraint stress than other treatments
      and OVX-EB + P treated rats had lower concentrations than the OVX-EB group,
      suggesting progesterone mitigated estradiol effects. Quantitative polymerase
      chain reaction experiments indicated that stress increased Fkbp5 mRNA in the
      ventral hippocampus, with no effect of stress or treatment on Nr3c1 (GR), Nr3c2
      (MR), Fkbp4, Bag1, or Ncoa1 (SRC-1) expression. Thus, the hypothesis is that
      estradiol effects on negative feedback are mediated by altered expression of
      receptor co-chaperones or co-modulators in the hippocampus was not supported.
      Estradiol may blunt feedback by limiting the availability of cytosolic GR
      protein.

PMID- 29189099
TI  - Creative prosthetic foot selection enables successful ambulation in stiletto high
      heels.
AB  - BACKGROUND: Walking in high heels presents biomechanical challenges, yet they
      remain part of many women's attire. However, women with a lower limb amputation
      are limited in available footwear options. Case description and methods: This
      case study is in response to one patient's assertion that she walked better and
      more symmetrically in heels than flat shoes with her below-knee prosthesis. She
      underwent gait analysis in athletic shoes and 10-cm stiletto high heels worn with
      a pediatric running foot to determine if these claims could be substantiated
      through biomechanical measures. Global gait asymmetry indices were calculated.
      Findings and outcomes: Asymmetry indices were nearly identical between athletic
      shoes and heels but joint-level findings differed substantially. Ankle mechanics
      were more symmetrical in heels but hip mechanics were less. CONCLUSION: The
      maintenance of symmetry in stiletto high heels does not imply maintenance of gait
      quality, as high heels are known to adversely affect some components walking
      mechanics. Clinical relevance Returning to high-heel wear is achievable for
      prosthesis users. Accommodations can be made using creativity in prosthetic foot
      selection to enable successful ambulation; however, attention to gait mechanics
      may be important for patient safety.

PMID- 29189100
TI  - A Soft Tube-Climbing Robot.
AB  - This article demonstrates a pneumatically actuated soft robot capable of
      navigating the inside of a tube. This robot was built using buckling pneumatic
      actuators (vacuum-actuated muscle-inspired pneumatic structures, or VAMPs). The
      tube climber can navigate through a tube with turns, inclines, and varying
      diameters. The robot is also able to remove obstacles (of more than 10 times its
      own weight) from tubes to perform a clearing function. It maintains climbing and
      clearing performance in wet conditions and under water. The tube climber is
      lightweight and completely soft and thus has the potential to be collaborative
      (i.e., work with humans) and also to interact safely with delicate environments.

PMID- 29189101
TI  - Pharmacokinetics and pharmacodynamics of the nucleoside sparing dual regimen
      containing rilpivirine plus darunavir/ritonavir in treatment-naive HIV-1-infected
      individuals.
AB  - BACKGROUND: We aimed at investigating the antiviral activity and the
      pharmacokinetics of the dual antiretroviral (ARV) combination of rilpivirine plus
      darunavir/ritonavir 25/800/100 mg once-daily in naive HIV-1-infected individuals
      (NHII) with different baseline viral loads. SETTINGS:
      Pharmacokinetic/pharmacodynamics study in ARV-naive HIV-infected individuals.
      METHODS: The primary endpoint was the number of NHII with HIV-RNA < 40 copies/mL
      at week 48. Secondary endpoints included rilpivirine/darunavir/ritonavir
      pharmacokinetics, HIV-RNA decay, and changes in ECG QT interval. RESULTS: Thirty
      six individuals were enrolled, 18 with a baseline viral load < 100,000 copies/mL
      (group A) and 18 with a baseline viral load > 100,000 copies/mL (group B). All
      but 1 (HIV-RNA = 63 copies/mL) subjects achieved viral load < 50 copies/mL by
      week 36, and all at week 48. Median (range) HIV-RNA reduction (Log10 copies/mL)
      was 1.3 (0.6-1.9) over the first week, with no differences between groups A and
      B. Geometric mean and 95%CI rilpivirine Cmax, Ctrough, AUC were 183 (165-239),
      114 (104-109) ng/mL, 2966 (2704-3820) ng h/mL. No QTcF interval changes were
      recorded. CONCLUSIONS: rilpivirine/darunavir/ritonavir could be efficacious, with
      limited short-term toxicity in ARV-naive patients. Although rilpivirine was co
      administered with ritonavir, its exposure was within ranges measured during phase
      III trials.

PMID- 29189103
TI  - Protein-protein interaction networks and different clustering analysis in
      Burkitt's lymphoma.
AB  - OBJECTIVE: Burkitt's lymphoma (BL) is a highly aggressive malignant lymphoma, its
      molecular biological mechanism has not been fully investigated. The construction
      of protein-protein interaction (PPI) networks and the identification of complexes
      through a cluster analysis are important research directions in the post-genome
      era. However, different cluster analysis algorithms have their own
      characteristics, and a single analysis has some limitations. In this study, we
      obtained the target and pathway information of BL using different clustering
      analyses. MATERIAL AND METHODS: First, we obtained 50 BL genes by screening the
      Online Mendelian Inheritance in Man (OMIM) database; their related genes were
      further extracted from the literature. The PPI network was constructed with the
      Search Tool for Retrieval of Interacting Genes/Proteins (STRING). Afterward, the
      interaction data were input in Cytoscape3.4.0 software and related plug-ins were
      used to implement topology analysis and clustering analysis. Functional analysis
      based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to
      characterize the biological importance of the clusters. RESULTS: We constructed a
      PPI network consisting of 459 nodes (proteins) and 1399 sides (interactions), 12
      genes and 8 signaling pathways were found to be closely related to BL.
      CONCLUSION: In this study, the use of combined algorithms to analyse gene
      interactions provides a new perspective for network-based analysis. The results
      of this study reveal new insights into the molecular mechanisms underlying BL,
      which may be novel therapeutic targets for disease management and may provide a
      bioinformatic basis for the further understanding of BL.

PMID- 29189102
TI  - Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in
      Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain
      Tumors Independent of Linear Gadolinium-based Contrast Agent Administration.
AB  - Purpose To determine whether whole-brain irradiation, chemotherapy, and primary
      brain pathologic conditions affect magnetic resonance (MR) imaging signal changes
      in pediatric patients independent of the administration of gadolinium-based
      contrast agents (GBCAs). Materials and Methods This institutional review board
      approved, HIPAA-compliant study included 144 pediatric patients who underwent
      intravenous GBCA-enhanced MR imaging examinations (55 patients with primary brain
      tumors and whole-brain irradiation, 19 with primary brain tumors and chemotherapy
      only, 52 with primary brain tumors without any treatment, and 18 with
      neuroblastoma without brain metastatic disease). The signal intensities (SIs) in
      the globus pallidus (GP), thalamus (T), dentate nucleus (DN), and pons (P) were
      measured on unenhanced T1-weighted images. GP:T and DN:P SI ratios were compared
      between groups by using the analysis of variance and were analyzed relative to
      group, total cumulative number of doses of GBCA, age, and sex by using
      multivariable linear models. Results DN:P ratio for the radiation therapy group
      was greater than that for the other groups except for the group of brain tumors
      treated with chemotherapy (P < .05). The number of GBCA doses was correlated with
      the DN:P ratio for the nontreated brain tumor group (P < .0001). The radiation
      therapy-treated brain tumor group demonstrated higher DN:P ratios than the
      nontreated brain tumor group for number of doses less than or equal to 10 (P <
      .0001), whereas ratios in the nontreated brain tumor group were higher than those
      in the radiation therapy-treated brain tumor group for doses greater than 20 (P =
      .05). The GP:T ratios for the brain tumor groups were greater than that for the
      neuroblastoma group (P = .01). Conclusion Changes in SI of the DN and GP that are
      independent of the administration of GBCA occur in patients with brain tumors
      undergoing brain irradiation, as well as in patients with untreated primary brain
      tumors. (c) RSNA, 2017.

PMID- 29189104
TI  - Radiation- and Age-Associated Changes in Peripheral Blood Dendritic Cell
      Populations among Aging Atomic Bomb Survivors in Japan.
AB  - Previous immunological studies in atomic bomb survivors have suggested that
      radiation exposure leads to long-lasting changes, similar to immunological aging
      observed in T-cell-adaptive immunity. However, to our knowledge, late effects of
      radiation on dendritic cells (DCs), the key coordinators for activation and
      differentiation of T cells, have not yet been investigated in humans. In the
      current study, we hypothesized that numerical and functional decreases would be
      observed in relationship to radiation dose in circulating conventional DCs (cDCs)
      and plasmacytoid DCs (pDCs) among 229 Japanese A-bomb survivors. Overall, the
      evidence did not support this hypothesis, with no overall changes in DCs or
      functional changes observed with radiation dose. Multivariable regression
      analysis for radiation dose, age and gender effects revealed that total DC counts
      as well as subpopulation counts decreased in relationship to increasing age.
      Further analyses revealed that in women, absolute numbers of pDCs showed
      significant decreases with radiation dose. A hierarchical clustering analysis of
      gene expression profiles in DCs after Toll-like receptor stimulation in vitro
      identified two clusters of participants that differed in age-associated
      expression levels of genes involved in antigen presentation and
      cytokine/chemokine production in cDCs. These results suggest that DC counts
      decrease and expression levels of gene clusters change with age. More than 60
      years after radiation exposure, we also observed changes in pDC counts associated
      with radiation, but only among women.

PMID- 29189105
TI  - Characterization of Diffuse Intrinsic Pontine Glioma Radiosensitivity using
      Synchrotron Microbeam Radiotherapy and Conventional Radiation Therapy In Vitro.
AB  - Synchrotron microbeam radiation therapy is a promising preclinical radiotherapy
      modality that has been proposed as an alternative to conventional radiation
      therapy for diseases such as diffuse intrinsic pontine glioma (DIPG), a
      devastating pediatric tumor of the brainstem. The primary goal of this study was
      to characterize and compare the radiosensitivity of two DIPG cell lines (SF7761
      and JHH-DIPG-1) to microbeam and conventional radiation. We hypothesized that
      these DIPG cell lines would exhibit differential responses to each radiation
      modality. Single cell suspensions were exposed to microbeam (112, 250, 560, 1,180
      Gy peak dose) or conventional (2, 4, 6 and 8 Gy) radiation to produce clonogenic
      cell-survival curves. Apoptosis induction and the cell cycle were also analyzed
      five days postirradiation using flow cytometry. JHH-DIPG-1 cells displayed
      greater radioresistance than SF7761 to both microbeam and conventional radiation,
      with higher colony formation and increased accumulation of G2/M-phase cells.
      Apoptosis was significantly increased in SF7761 cells compared to JHH-DIPG-1
      after microbeam irradiation, demonstrating cell-line specific differential
      radiosensitivity to microbeam radiation. Additionally, biologically equivalent
      doses to microbeam and conventional radiation were calculated based on clonogenic
      survival, furthering our understanding of the response of cancer cells to these
      two radiotherapy modalities.

PMID- 29189106
TI  - Nonlinear Tracking Control of a Conductive Supercoiled Polymer Actuator.
AB  - Artificial muscle actuators made from commercial nylon fishing lines have been
      recently introduced and shown as a new type of actuator with high performance.
      However, the actuators also exhibit significant nonlinearities, which make them
      difficult to control, especially in precise trajectory-tracking applications. In
      this article, we present a nonlinear mathematical model of a conductive
      supercoiled polymer (SCP) actuator driven by Joule heating for model-based
      feedback controls. Our efforts include modeling of the hysteresis behavior of the
      actuator. Based on nonlinear modeling, we design a sliding mode controller for
      SCP actuator-driven manipulators. The system with proposed control law is proven
      to be asymptotically stable using the Lyapunov theory. The control performance of
      the proposed method is evaluated experimentally and compared with that of a
      proportional-integral-derivative (PID) controller through one-degree-of-freedom
      SCP actuator-driven manipulators. Experimental results show that the proposed
      controller's performance is superior to that of a PID controller, such as the
      tracking errors are nearly 10 times smaller compared with those of a PID
      controller, and it is more robust to external disturbances such as sensor noise
      and actuator modeling error.

PMID- 29189107
TI  - The Psychology Behind Population Health Management.

PMID- 29189108
TI  - Return to work after young stroke: A systematic review.
AB  - Background The incidence of stroke in young adults is increasing. While many
      young survivors are able to achieve a good physical recovery, subtle dysfunction
      in other domains, such as cognition, often persists, and could affect return to
      work. However, reported estimates of return to work and factors affecting
      vocational outcome post-stroke vary greatly. Aims The aims of this systematic
      review were to determine the frequency of return to work at different time points
      after stroke and identify predictors of return to work. Summary of review Two
      electronic databases (Medline and Embase) were systematically searched for
      articles according to Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines. A total of 6473 records were screened, 68 were assessed for
      eligibility, and 29 met all inclusion criteria (working-age adults with stroke,
      return to work evaluated as an outcome, follow-up duration reported, and
      publication within the past 20 years). Return to work increased with time, with
      median frequency increasing from 41% between 0 and 6 months, 53% at 1 year, 56%
      at 1.5 years to 66% between 2 and 4 years post-stroke. Greater independence in
      activities of daily living, fewer neurological deficits, and better cognitive
      ability were the most common predictors of return to work. Conclusion This review
      highlights the need to examine return to work in relation to time from stroke and
      assess cognition in working age and young stroke survivors. The full range of
      factors affecting return to work has not yet been explored and further
      evaluations of return to work interventions are warranted.

PMID- 29189109
TI  - Monocentric experience of leadless pacing with focus on challenging cases for
      conventional pacemaker.
AB  - AIM: Leadless cardiac pacemaker has been developed to reduce complications
      related to cardiac pacing and is considered as an alternative to conventional
      pacemaker although safety and efficacy data in clinical practice are limited. The
      purpose of this study was to investigate the safety and efficacy profile of Micra
      Transcatheter Pacing System (TPS) used in daily clinical activity with a focus on
      challenging cases for conventional pacing. METHODS: A total of 66 patients (46
      men, 79.1 +/- 9.7 years) having a Class I or II indication for ventricular pacing
      underwent a Micra TPS implant procedure. All patients were enrolled in a
      prospective registry. Follow-up visits were scheduled at discharge and after 1,
      3, 6 and 12 months. RESULTS: Primary indication for pacing was third degree
      atrioventricular block (30.3%), sinus node dysfunction (21.2%) or permanent
      atrial fibrillation with bradycardia (45.5%). The device was successfully
      implanted in 65 patients (98.5%). During follow-up of 10.4 +/- 6.1 months (range
      1-23 months), electrical measurements remained stable. Mean pacing capture
      threshold, pacing impedance and R-wave sensing were respectively 0.57 +/- 0.32 V,
      580 +/- 103 Ohms, 10.62 +/- 4.36 mV at the last follow-up. One major (loss of
      function) and three minor adverse events occurred. Pericardial effusion,
      dislodgement, device related infection or pacemaker syndrome were not observed.
      Micra TPS implantation was straightforward for patients with congenital or
      acquired cardiac and/or vascular abnormalities, previous tricuspid surgery and
      after heart transplantation. CONCLUSION: Our experience confirms that
      implantation of Micra is safe and efficient in a real world population including
      patients who present a challenging condition for conventional pacing.

PMID- 29189110
TI  - Protecting safe abortion in humanitarian settings: overcoming legal and policy
      barriers.
AB  - Women and girls are increasingly the direct and targeted victims of armed
      conflict and studies show that they are disproportionately and differentially
      affected. However, humanitarian laws, policies, and protocols have yet to be
      meaningfully interpreted and adapted to respond to their specific needs,
      including to sexual and reproductive health services and rights. In particular,
      safe abortion services are routinely omitted from sexual and reproductive health
      services in humanitarian settings for a variety of reasons, including improper
      deference to national law, the disproportionate influence of restrictive funding
      policies, and the failure to treat abortion as medical care. However, properly
      construed, abortion services fall within the purview of the universal and non
      derogable protections granted under international humanitarian and human rights
      law. This commentary considers the protections of international humanitarian law
      and explains how abortion services fall within a category of protected medical
      care. It then outlines contemporary challenges affecting the realisation of these
      rights. Finally, it proposes a unification of current approaches through the use
      of international humanitarian law to ensure comprehensive care for those affected
      by armed conflict.

PMID- 29189111
TI  - Technical-environmental optimisation of the activated carbon production of an
      agroindustrial waste by means response surface and life cycle assessment.
AB  - In this study, a simultaneous optimisation of technical and environmental
      parameters for activated carbon production from soybean shells is presented. A 23
      factorial design was developed to explore the performance of the technical
      responses yield and iodine number, and the single score of ReCiPe endpoint
      method, which was evaluated by means the life cycle assessment. The independent
      factors included in the design of experiments were the impregnation ratio,
      temperature, and time activation. Three quadratic equations were obtained and
      simultaneously optimised by maximisation of the overall desirability function.
      The principal results of the individual responses indicate that the iodine number
      is practically independent of the activation temperature in a range of 450 oC-650
      oC; the yield is inversely proportional to activation time and exhibits minimum
      values between 500 oC-600 oC; and the environmental response single score
      presents the lowest value at a temperature and time activation of 450 oC and 30
      min, respectively. The most polluting stage of activated carbon production from
      soybean shells production is the impregnation stage, mainly for the use of ZnCl2
      as activating agent and the energy consumption. The simultaneous optimisation of
      the three responses indicates that the optimal activated carbon should be
      produced at 180 min, 650 oC, and an impregnation ratio of 1 g soybean shell g
      ZnCl2-1.

PMID- 29189113
TI  - Bacterial outer membrane vesicles: New insights and applications.
AB  - Outer membrane vesicles (OMVs) (~50-250 nm in diameter) are produced by both
      pathogenic and nonpathogenic bacteria as a canonical end product of secretion. In
      this review, we focus on the OMVs produced by gram-negative bacteria. We provide
      an overview of the OMV structure, various factors regulating their production,
      and their role in modulating host immune response using a few representative
      examples. In light of the importance of the diverse cargoes carried by OMVs, we
      discuss the different modes of their entry into the host cell and advances in the
      high-throughput detection of these OMVs. A conspicuous application of OMVs lies
      in the field of vaccination; we discuss its success in immunization against human
      diseases such as pertussis, meningitis, shigellosis and aqua-farming endangering
      diseases like edwardsiellosis.

PMID- 29189114
TI  - Meet Our Associate Editor.

PMID- 29189115
TI  - Editorial: Computer-assisted Vaccine Design (CAVD) Approach can Help in the
      Management of the Emerging H7N9 Influenza Virus.

PMID- 29189116
TI  - ScFv Improvement Approaches.
AB  - The most common recombinant antibody format is the single chain fragment variable
      (scFv) which it contains the complete antigen-binding domains of an intact
      antibody. ScFv fragments have found vast medical and non-medical applications.
      Several approaches have been employed to increase the affinity, avidity and
      structural stability related to these antibody fragments. Most approaches related
      to scFv improvement have been included in this review.

PMID- 29189117
TI  - In Silico Prediction of P-glycoprotein Binding: Insights from Molecular Docking
      Studies.
AB  - The P-glycoprotein is an efflux transporter that expels substances out of the
      cells and has an important impact in the pharmacokinetic and pharmacodynamic
      properties of drugs. The study of the interactions between ligands and the P
      glycoprotein has implications in the design of Central Nervous System drugs and
      their transport across the blood-brain barrier. Moreover, since the P
      glycoprotein is overexpressed in some types of cancers, the protein is
      responsible for expelling the drug therapies from the cells, and hence, for drug
      resistance. In this review we describe different P-glycoprotein binding sites
      reported for substrates, inhibitors and modulators, and focus on molecular
      docking studies that provide useful information about drugs and P-glycoprotein
      interactions. Docking in crystallized structures and homology models showed
      potential in the detection of the binding site and key residues responsible for
      ligand recognition. Moreover, virtual screening through molecular docking
      discriminates P-glycoprotein ligands from decoys. We also discuss challenges and
      limitations of molecular docking simulations applied to this particular protein.
      Computational structure-based approaches are very helpful in the study of novel
      ligands that interact with the P-glycoprotein and provide insights to understand
      the P-glycoprotein molecular mechanism of action. '.

PMID- 29189118
TI  - Metals and Parkinson's Disease: Mechanisms and Biochemical Processes.
AB  - Genetic background accounts for only 5 to 10% of the reported cases of
      Parkinson's disease (PD), while the remaining cases are of unknown etiology. It
      is believed that environmental factors may be involved in the causality of a
      large proportion of PD cases. Several PD genes are activated by xenobiotic
      exposure, and a link between pesticide exposure and PD has been demonstrated.
      Many epidemiological studies have shown an association between PD and exposure to
      metals such as mercury, lead, manganese, copper, iron, aluminum, bismuth,
      thallium, and zinc. This review explores the biological effects, the pathogenetic
      processes, genetic susceptibilities to metals as well as examining future
      strategies for PD treatment, such as chelation therapy.

PMID- 29189119
TI  - Journey of 2'-deoxy-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU):
      from Antiviral Drug to PET Imaging Agent.
AB  - BACKGROUND: Developed as an antiviral drug in the 1960s and 1970s, the thymidine
      analogue 2'-deoxy-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU) was
      translated to clinical application for treatment of herpes simplex virus
      infection. In phase I clinical trial of FMAU; however, patients experienced
      neurotoxicity at the pharmacological dose, and FMAU was withdrawn from the trial.
      More recently, FMAU has been developed as a tracer for positron emission
      tomography (PET) imaging in early detection of cancer through its binding to
      human thymidine kinase, which is upregulated in cancer cells. FMAU radiolabeled
      with 11C or 18F has been examined for PET imaging of tumor cell proliferation and
      DNA synthesis. Although many reports have been partially published on FMAU,
      systematic reviews outlining the historic development and imaging probe are
      lacking. This review is focused on the identification of kinases, the chemistry
      of FAMU and its application in cancer diagnosis and therapy assessment.
      OBJECTIVE: The aim of this study was to review the historic development of FMAU,
      from its synthetic development and antiviral activity studies to its
      radiolabeling and evaluate it as a PET imaging probe for the early detection of
      cancer and assessment of treatment response, including published reports on the
      clinical utility of 18F-FMAU. CONCLUSION: While FMAU was not successful as an
      antiviral agent, 18F-FMAU is a suitable radiotracer for early detection of cancer
      and assessment of response to therapy by PET. The process of clinical grade 18F
      FMAU production requires further improvement. 18F-FMAU has high potential for
      clinical application, but further extensive studies are needed to establish this
      tracer in the diagnosis of various cancers and assessment of their response to
      therapy.

PMID- 29189120
TI  - Critical Role of IL-8 Targeting in Gliomas.
AB  - BACKGROUND: Glioma is a heterogeneous, highly complicated central nervous system
      (CNS) tumor with uncertain mechanism of initiation and progression, resulting in
      an unfavorable outcome. An extended network of cytokines is recognized as a major
      regulator of glioma pathogenesis, either promoting or inhibiting glioma
      progression based on their type and specificity. Interleukin-8 (IL-8) has been
      revealed as a critical regulator of CNS function and development with
      participation in many CNS disorders including gliomas. OBJECTIVE: The aim of the
      present review is to address the role of IL-8 in glioma pathogenesis focusing on
      the implicated molecular pathways as well as on its potential targeting for
      glioma therapy. METHODS AND RESULTS: PubMed-Medline, SCOPUS, and Google Scholar
      databases were searched for pre-clinical and clinical studies related to IL-8
      implication in gliomagenesis and IL-8 targeting strategies for gliomas.
      Literature data indicate that IL-8 participates in glioma angiogenesis and cell
      migration and it can serve as a potential biomarker, for early diagnosis, follow
      up and response to therapy. CONCLUSION: Several promising approaches that target
      directly or indirectly IL-8 effects in gliomas are currently in progress while
      more-in-depth studies are needed to validate its biomarker role and elucidate the
      underlying molecular mechanisms.

PMID- 29189121
TI  - The Development of Biologically Important Spirooxindoles as New Antimicrobial
      Agents.
AB  - BACKGROUND: Antibiotic resistance is one of the biggest threats to global health
      today, leading to higher medical costs and increased mortality. Because of the
      emergence and rapid spread of new resistance mechanisms globally, a growing
      number of infections are becoming harder to treat as the antibiotics used to
      treat them become less effective. Therefore, the development of new effective
      antimicrobial agents is still urgently needed. In last decades, a large number of
      structurally novel spirooxindoles have been synthesized mainly based on the ylide
      intermediates generated in situ and further assessed for their antimicrobial
      activity against different types of bacteria, leading to the discovery of some
      potent lead compounds with antimicrobial potentials. OBJECTIVE: The aim of this
      review to submarize recent advances on the synthesis, structure- activity
      relationship studies (SARs) and antimicrobial activity of spirooxindoles.
      METHODS: Peer-reviewed research work on spirooxindoles with antimicrobial
      activity were downloaded from bibliographic databases and analyzed based on their
      chemoptypes. RESULTS: 50 papers were retrieved from the literature databases, of
      which 20 papers described the synthesis and antimicrobial activity of
      spirooxindoles. CONCLUSION: This review highlights the importance of
      spirooxindoles as potential antimicrobial agents. The antimicrobial activity of
      spirooxindoles against different types of bacteria is less studied, mainly
      centering on primary antimicrobial assessment, some of these compounds have
      showed interesting antimicrobial activity. However, the current study is only
      limited to primary antimicrobial assessment, no detailed modes of action are
      investigated.

PMID- 29189122
TI  - Synthetic Polymer-based Electrospun Fibers: Biofunctionalization Strategies and
      Recent Advances in Tissue Engineering, Drug Delivery and Diagnostics.
AB  - BACKGROUND: Over the last decades, synthetic polymer-based electrospun
      nano/microfibers have emerged as potent materials in crucial biomedical
      applications such as tissue engineering, drug delivery and diagnostics. This is
      mainly attributed to versatility and reproducibility of the electrospinning (ES)
      process, as well as the high surface- to-volume ratio of the generated
      nanostructures. Appropriate functionalization with dedicated biomolecules (i.e.
      cell adhesive peptides, therapeutic molecules, bio-probes) is a critical
      requirement for the performances of such materials in their related application.
      METHODS: We report on the different chemical methodologies for preparing
      biofunctionalized synthetic polymer fibers, on the basis of two main approaches:
      biomolecule introduction after ES process (post-ES) and before ES (pre-ES). We
      then focused on the latest implications of such materials in areas of tissue
      engineering, drug delivery and diagnostics. RESULTS: This review describes the
      numerous immobilization strategies (either covalent or non-covalent) developed
      for designing biofunctionalized fibers, as well as their impact on their
      properties in dedicated application. The inputs of advanced conjugation tools
      ("clickable" chemistries, PEG linkers) for biofunctionalization are also
      highlighted. In the light of the literature, it appears that increasing research
      efforts are now devoted to multifunctional character and fiber combination with
      other materials (hydrogels, inorganic particles, microfluidic devices) for
      improved and tunable performances. CONCLUSION: Owing to flexibility and
      robustness of ES process as well as advances in conjugation and polymer/material
      engineering, high degree of control over biofunctionalization can now be
      achieved, to fit as best as possible the requirements of the targeted
      application. The performances reached up to now augur well for the future of such
      class of materials.

PMID- 29189123
TI  - Anti-Aging Drugs - Prospect of Longer Life?
AB  - BACKGROUND: Aging is a natural part of human life. However, recent discoveries
      indicate that pharmacological approaches used for the improvement and possibly,
      for the delay of the aging process, might shed a new light on this topic. This
      might obviously contribute to the extension of the active life of older people
      and maintenance of their quality of life, which could consequently reduce both
      social and economic burden of each country, especially the developed ones.
      OBJECTIVE: The purpose of this study is to explore pharmacological discoveries
      which may help to the delay or improvement of the aging process. More
      specifically, the authors focus on three anti-aging drugs candidates: metformin,
      rapamycin and resveratrol and one anti-aging component NAD+ precursors whose
      randomized control trials on animals have appeared to provide some efficacy in
      this respect and they seem to be promising in the aging process of human beings.
      METHODS: This was done by conducting a literature review of available sources
      describing the issue of aging process with special focus on those anti-aging drug
      candidates. RESULTS: The results of this study indicate that promising anti-aging
      candidates seem to be metformin, especially as far as cardiovascular or cancer
      mortality is concerned, and NAD+ precursors since they appear to promote better
      organ function, increased physical resistance, disease resistance and prolonged
      life expectancy. CONCLUSION: There is a call for more longitudinal clinical
      trials, which would prove the efficacy of the promising anti-aging drugs
      candidates in humans.

PMID- 29189124
TI  - Overview on Anticancer Drug Design and Development.
AB  - BACKGROUND: Many impediments of current anti-cancer therapies have urged
      scientists to discover new agents. As a result of growing spectrums of new
      targets and strategies and recent biological and biotechnological progresses,
      many anti-cancer agents such as monoclonal antibodies, small molecule tyrosine
      kinase inhibitors and epigenetic drugs have been reached to clinical trials.
      OBJECTIVES: This review helps to understand the rationale for the development of
      inhibitors against major targets such as cell growth, proliferation, survival,
      angiogenesis and recent targets such as proteasome, heat shock proteins, and
      epigenetics. METHODS: Recent approaches of the target-based anti-cancer drug
      developments were highlighted to giving some examples from approved agents. Many
      factors, such as metabolic change, hypoxia, cancer precursors and cancer
      resistant cells, and their effect on drug resistance mechanisms were discussed.
      The impacts of advanced computational techniques to identify targets of cancer
      and designing more selective inhibitors were explained. RESULTS: Contributions of
      recent techniques such as a network analysis, the precise modes of action and
      computational methodologies especially simulation of bio-molecular processes to
      clarify targets, mechanism actions and reasons of lack of efficacy of anti-cancer
      drugs have been explained. The relationship between the several mechanisms and
      molecular design strategies has been discussed. CONCLUSION: This review provides
      an overview of important targets and design strategies of anti-cancer drugs,
      advantages and disadvantages of these methods and evaluation of some currently
      used anticancer targets in clinical studies.

PMID- 29189125
TI  - Use of antibiotic loaded biomaterials for the management of bone prosthesis
      infections: rationale and limits.
AB  - BACKGROUND: Periprosthetic joint infection still represents a challenging issue
      for the orthopedic community. In the United States approximately a million joint
      arthroplasties are performed each year, with infection rates ranging from 1 to
      2%: revisions has significant implications in health care costs and appropriate
      resources management. The use of locally applied antibiotics as a prophylaxis
      measure or as a component of the therapeutic approach in primary or revision
      surgery is finalized at eliminating any microorganism and strengthening the
      effectiveness of systemic therapy. OBJECTIVE: The present review of clinical and
      preclinical in vivo studies tried to identify advantages and limits of the
      materials used in the clinical orthopedic practice and discuss developed
      biomaterials, innovative therapeutic approaches or strategies to release
      antibiotics in the infected environment. METHOD: A systematic search was carried
      out by two independent observers in two databases (www.pubmed.com and
      www.scopus.com) in order to identify pre-clinical and clinical reports in the
      last 10 years. RESULTS: 71 papers were recognized eligible: 15 articles were
      clinical studies and 56 in vivo studies. CONCLUSION: Polymethylmethacrylate was
      the pioneer biomaterial used to manage infections after total joint replacement.
      Despite its widespread use, several issues still remain debated: the methods to
      combine materials and antibiotics, the choice of antibiotics, releasing kinetics
      and antibiotics efficacy. In the last years, the interest was directed towards
      the selection of different antibiotics, loaded in association of more than only
      one class, and biomaterials with special focus on delivery systems as implant
      surface coatings, hydrogels, ceramics, micro-carriers, microspheres or
      nanoparticles.

PMID- 29189126
TI  - Recent Advances for the Synthesis of Selenium-containing Small Molecules as
      Potent Antitumor Agents.
AB  - Selenium-containing small molecules have attracted considerable attention of
      chemical and medicinal researchers owing to their various biological activities,
      such as antitumor effects, cardiovascular protection, antibacterial or antiviral
      effects, immunoregulation and nerve protection, among which the most promising
      area is antineoplasm. In the past several decades, different kinds of
      organoselenium compounds, such as selenides, seleno(iso)cyanates, substituted
      selenoureas, selenious esters and Se-containing heterocycles have been reported
      as candidates of anti-cancer agents. Current reviews of Se-containing anticancer
      compounds mainly concerned about the investigation of their bioactivities,
      whereas, few attention has been addressed on their synthetic approaches. Herein,
      we summarized methodologies recently developed to synthesize organoselenium
      compounds with potent antineoplastic properties, which would be helpful for
      further design and synthesis of new bioactive Se-containing molecules with
      diverse structural features.

PMID- 29189127
TI  - Biosimilars: From Extrapolation into Off Label Use.
AB  - BACKGROUND: Biologic drugs have revolutionised the management of many
      inflammatory conditions. Patent expirations have stimulated development of highly
      similar but non-identical molecules, the biosimilars. Extrapolation of
      indications is a key concept in the development of biosimilars. However, this has
      been met with concerns around mechanisms of action, equivalence in efficacy and
      immunogenicity, which are reviewed in this article. METHODS: Narrative overview
      composed from literature search and the authors' experience. Literature search
      included Pubmed, Web of Science, and online document archives of the Food and
      Drug Administration and European Medicines Agency. RESULTS: The concepts of
      biosimilarity and extrapolation of indications are revisited. Concerns around
      extrapolation are exemplified using the biosimilar infliximab, CT-P13, focusing
      on mechanisms of action, immunogenicity and trial design. The opportunities and
      cautions for using biologics and biosimilars in unlicensed inflammatory
      conditions are reviewed. CONCLUSIONS: Biosimilars offer many potential
      opportunities in improving treatment access and increasing treatment options. The
      high cost associated with marketing approval means that many bio-originators may
      never become licenced for rarer inflammatory conditions, despite clinical
      efficacy. Biosimilars, with lower acquisition cost, may improve access for off
      label use of biologics in the management of these patients. They may also provide
      opportunities to explore off-label treatment of conditions where biologic therapy
      is less established. However, this potential advantage must be balanced with the
      awareness that off-label prescribing can potentially expose patients to risky and
      ineffective treatments. Post-marketing surveillance is critical to developing
      long-term evidence to provide assurances on efficacy as well as safety.

PMID- 29189128
TI  - Curcumin as an Adjunct Therapy and microRNA Modulator in Breast Cancer.
AB  - BACKGROUND: Pathogenesis of breast cancer is paralleled by distinct alterations
      in the expression profile of several microRNAs (miRNAs). Recent studies have
      shown that miRNAs can serve as diagnostic and prognostic markers, and also as
      therapeutic targets in breast cancer. Curcumin is a biologically active dietary
      polyphenol that has emerged with strong anti-tumor properties that are also
      documented in breast cancer. METHODS: A multi-database electronic search was
      performed to provide an overview of curcumin as an adjunct therapy and miRNA
      modulator in breast cancer and highlight the significance of observations for the
      treatment of cancer therapies. RESULTS: The putative anti-tumor properties of
      curcumin are mediated by diverse mechanisms including inhibition of cell
      proliferation, metastasis, migration, invasion and angiogenesis, and induction of
      G2/M cell cycle arrest, apoptosis and paraptosis. Recent evidence implies that
      curcumin can interact with several oncogenic and tumorsuppressive miRNAs involved
      in different stages of breast cancer. In this context, up-regulation of miR181b,
      miR-34a, miR-16, miR-15a and miR-146b-5p, and down-regulation of miR-19a and miR
      19b have been shown following the treatment of several breast cancer cell lines
      with curcumin. These effects lead to the suppression of tumorigenesis and
      metastasis, and induction of apoptosis. CONCLUSION: Curcumin appears as an
      important miRNA modulator in breast cancer. However, further investigations are
      warranted to elucidate the impact of curcumin on miRNA transcriptome profile of
      breast cancer and the resulting impact of experimental models.

PMID- 29189129
TI  - FDG PET/CT Imaging in Diabetic Patients - A Special Emphasis on Imaging of
      Infection.
AB  - Nuclear Medicine (NM) imaging plays a major role in the assessment of infection
      and inflammation. Tracers, including single photon emitting radionuclides for
      Single Photon Emission Tomography (SPECT) and agents for positron emission
      tomography (PET), reflect primarily tissue and cellular function or metabolism.
      In the specific clinical setting of a patient with suspected infectious or
      inflammatory process, planar scintigraphy, SPECT or PET procedures are used to
      support a clinically suspected diagnosis. Integrating metabolic and anatomic
      information using a single SPECT/CT or PET/CT technique has substantially
      improved the diagnostic accuracy of these imaging tests and advanced the NM
      technology to be a significant and important tool in the field of infection and
      inflammation. Diabetes, one of the most prevalent diseases, has a direct
      relationship with the development of various infection related condition. Due to
      alterations in different metabolic pathways, imaging of the diabetic patient may
      be subject to specific pitfalls and obstacles which should be taken into
      consideration. This review aimed at describing the impact of diabetes and
      hyperglycemia on NM imaging, with an emphasis on FDGPET/ CT, in specific
      infectious conditions related to diabetes.

PMID- 29189130
TI  - Nuclear Medicine Imaging in Fever of Unknown Origin: The New Paradigm.
AB  - Fever of Unknown Origin, or FUO, is a challenging condition for patients and
      clinicians. In up to 50% of cases, no diagnosis is established. Patient workup
      begins with comprehensive history, physical examination and laboratory tests.
      Radionuclide imaging has been a second-line procedure. Gallium-67 citrate, which
      accumulates in infection, inflammation, and tumor, was for many years, the
      radionuclide test of choice in the workup of FUO. The 24-72 hours between
      injection and imaging, relatively high radiation dose to patients, and suboptimal
      image quality are significant disadvantages; imaging results are variable.
      Although labeled leukocyte imaging accurately localizes infection, infections
      cause only about 20%-40% of all FUO's. In most cases, this test is not helpful in
      identifying the source of the fever. Fluorine-18-fluorodeoxyglucose (FDG) uptake
      is related to cellular glucose metabolism. Increased FDG uptake is present in
      numerous hypermetabolic conditions, including tumor, infection, and noninfectious
      inflammation. FDG positron emission tomography (PET) and PET/computed tomography
      (CT) have rapidly assumed an increasingly important role in the diagnostic workup
      of patients with FUO. FDG is especially useful for localizing lesions and areas
      of interest for further evaluation. In contrast to gallium and labeled leukocyte
      imaging, FDG contributes useful information in children with FUO. Initially
      utilized as a second-line diagnostic tool in patients with FUO, recent data
      indicate that FDG contributes more diagnostically useful information than
      anatomic imaging like ultrasound and CT, which leads to earlier institution of
      appropriate therapy. These findings suggest that FDG imaging should be performed
      earlier, rather than later, in the diagnostic evaluation of the patient with FUO.

PMID- 29189131
TI  - Past and Future of Ga-citrate for Infection and Inflammation Imaging.
AB  - Both 67Ga and 68Ga-citrates are used to detect a wide spectrum of pathology
      consisting of various inflammatory, infectious and malignant conditions.
      Considering the now widespread availability and constantly increasing demand for
      PET/CT studies,68Ga-citrate is gaining ground in clinical settings and the added
      value of combined metabolic and anatomical imaging achieved by combining PET with
      Computed Tomography (CT) to PET/CT makes 68Ga-citrate particularly promising.
      Despite the tracer's non-specificity, it has demonstrated potential especially in
      the evaluation of various infectious and inflammatory skeletal- and lung
      conditions. In this review, we will focus on the indications and lessons learned
      from 67Ga, and present the current status for the use of 68Ga-citrate PET/CT in
      selected inflammation and infectious diseases based on the limited literature
      available.

PMID- 29189132
TI  - Polyphenols: Novel Signaling Pathways.
AB  - BACKGROUND: Cardiovascular disease (CVD) is currently the leading cause of death
      globally. The metabolic syndrome (MetS), a clustering of risk factors including
      hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol,
      reduced high-density lipoprotein (HDL) cholesterol and increased visceral
      adiposity, is a significant risk factor for the development of CVD. Non-alcoholic
      fatty liver disease (NAFLD), often referred to as the hepatic manifestation of
      MetS, is a constellation of progressive liver disorders closely linked to
      obesity, diabetes, and insulin resistance. NAFLD initially presents as relatively
      benign, non-progressive hepatic steatosis, but it may, in certain individuals,
      progress to nonalcoholic steatohepatitis, fibrosis, cirrhosis, or hepatocellular
      carcinoma. Currently, there are no validated treatments for NAFLD. Polyphenols
      are important bioactive dietary compounds and may represent a natural
      complementary and integrative therapy for the treatment of CVDassociated risk
      factors, including elevated serum cholesterol and triglyceride levels, as well as
      NAFLD. Understanding their molecular mechanisms of action is important in the
      design of future human intervention studies. METHODS: Several studies utilizing
      in vitro and in vivo models have helped to identify underlying molecular
      mechanisms of action of polyphenols. RESULTS: This review will highlight recent
      advances regarding the molecular actions of dietary procyanidins, with a special
      focus on those originating from procyanidin-rich grape seed extracts, with a
      focus on the signaling pathways utilized to exert beneficial metabolic effects.
      CONCLUSION: Modulation of nuclear receptor activity and histone deacetylase
      inhibition has been identified as underlying mechanisms contributing to
      procyanidin-mediated amelioration of dyslipidemia and steatosis.

PMID- 29189133
TI  - Risk Assessment and Monitoring of Antibody Responses to Biosimilars in Chronic
      Inflammatory Diseases.
AB  - The expiry of the patent of several leading biological medicinal products has led
      to a surge in the development of 'biosimilar' products. However, in contrast to
      generic small-molecule medicines, biosimilars are not identical to their
      reference medicinal products. Full comparability in quality as well as in
      preclinical and clinical issues is required to register a biosimilar. The
      potential to induce antidrug antibodies after treatment with biological medicinal
      products is a safety issue that is an important consideration in the development
      of biosimilars and a critical aspect of regulatory filings. Regulatory
      authorities in the European Union require antidrug antibody responses to be
      evaluated and to be approached from a safety perspective: the higher the
      potential of immunogenicity to adversely affect a patient's health, the more
      diligently one should clarify the immunogenicity of the product. So far, however,
      no specific recommendations were given on a method for risk assessment or on the
      extent of the requisite antidrug antibody characterization. In this review, we
      will discuss the current state of knowledge on biosimilar products of infliximab,
      adalimumab and etanercept and present risk level-based schemes for the
      investigations of antidrug antibodies in non-clinical, clinical and
      pharmacovigilance studies.

PMID- 29189134
TI  - The Economic Impact of Biosimilars on Chronic Immune-Mediated Inflammatory
      Diseases.
AB  - BACKGROUND: Biological drugs represent highly effective but costly treatments for
      chronic immunemediated inflammatory diseases posing substantial burden on health
      care budgets. Introduction of biosimilars since 2013 has brought forward the
      potential of market competition, and as a societal benefit, the hope of increased
      access at a lower cost. OBJECTIVE: We aim to provide a descriptive review on
      economic aspects and market changes related to the introduction of biosimilar
      drugs. METHOD: Our focus is on chronic immune-mediated inflammatory conditions in
      rheumatology, gastroenterology and dermatology. Based on available literature
      data, we discuss the determinants of access to biological treatment, summarize
      the available health economic evidences with special focus on cost-utility and
      budget impact analyses. Market penetration of biosimilars and their overall
      impact on biological markets are analyzed. RESULTS: Biosimilar markets are
      country specific due to differences in the regulatory and reimbursement systems.
      Cost-utility analyses suggest, that given the lower price of biosimilars,
      formerly established biological treatment sequence practices and the eligibility
      criteria for biological treatment deserve reconsideration. Budget impact analyses
      forecasted significant budget savings in various diagnoses and countries,
      providing opportunity for the treatment of more patients. CONCLUSION: Biosimilars
      may contribute to better patient-access and provide savings to governments. To
      increase their acceptability, further clinical evidences and real world
      experiences are needed, as well as education of physicians and patients. The high
      biosimilar penetration rates in Norway, Denmark and Poland suggest that policies
      which support interchanging from the reference product may be important drivers
      of biosimilar uptake.

PMID- 29189135
TI  - The Experience with Biosimilars of Infliximab in Rheumatic Diseases.
AB  - BACKGROUND: Infliximab biosimilars are the first biosimilars of monoclonal
      antibodies approved by the main regulatory agencies. Up to the present day, two
      infliximab biosimilars have been approved: CT-P13 (Celltrion), and SB2 (Biogen),
      but other companies have been developing candidate infliximab biosimilars that
      are on clinical trials: PF 06438179 (Pfizer), the ABP710 (bioCentury/Amgen) the
      BCD055 (JSC Biocad Russica) and BOW015 (Epirus). METHODS: We have made a
      literature search in MedLine database using the key words [Infliximab] and
      [biosimilars] and [rheumatic diseases] and [rheumatisms]. We have also made a
      search in the clinicaltrials.org website. CONCLUSIONS: Clinical data published so
      far have provided important evidence on long-term efficacy and safety,
      immunogenicity and switching, supporting the use of CT-P13 and SB2 for the
      treatment of rheumatic diseases. In addition, the European experience has proved
      the economic advantages of the incorporation of infliximab biosimilars in
      clinical practice. Despite the widespread use of infliximab biosimilars there is
      still a lack of data regarding interchangeability between reference products and
      biosimilars.

PMID- 29189136
TI  - The Role of Biosimilars in Patient Access to Therapeutic Antibodies for Immune
      Mediated Inflammatory Diseases.
AB  - BACKGROUND: Biosimilars have the potential to create competition, lower costs,
      and increase patient access to biological medications. However, biological
      medications are sensitive to their manufacturing processes and difficult to
      precisely characterize, leading to questions about substitution and
      interchangeability among products. METHODS: This article reviews the role of
      biosimilars in patient access to therapeutic antibodies. RESULTS: Although
      pathways for the approval of biosimilars have been developed, important issues
      remain unresolved. Interchangeability, or the designation of one medicine as
      clinically similar to and/or substitutable for another, is specified in some
      countries but restricted or awaiting policy resolution in others. Non-medical
      switching, or the switching among biological medications to select a less
      expensive product, for reasons unrelated to patient health and safety, is
      controversial because of the potential for complications related to repeated
      switching (e.g., immunogenicity and loss of therapeutic effect), and transfer of
      prescribing responsibility for patient medications from the physician to the
      insurance company. Although biosimilars have different names in different
      countries, the World Health Organization (WHO) calls for nomenclature that
      incorporates the international nonproprietary name of the original biological
      medication followed by a distinguishing suffix qualifier. Naming consistency
      across countries seems sensible, and adoption of the WHO recommended suffix would
      greatly simplify pharmacovigilance. CONCLUSIONS: Support for the WHO proposal is
      advised by numerous stakeholders, and resolution of the remaining outstanding
      issues is urged so that patients and physicians can safely access biosimilars.

PMID- 29189137
TI  - Platform for Lipid Based Nanocarriers' Formulation Components and their Potential
      Effects: A Literature Review.
AB  - BACKGROUND: Lipid based nanocarriers have gained recently enormous interest for
      pharmaceutical application. They have the potential to provide controlled drug
      release and to target the drug to a specific area. In addition, lipid based
      nanocarriers can improve the bioavailability of drugs suffering from high hepatic
      first-pass metabolism, by enhancing their transport via the lymphatic system. The
      main components of lipid based nanocarriers are lipids and surfactants. Both have
      great influence on the prepared lipid based systems characteristics. The criteria
      for their selection are much related to physicochemical properties of the drug
      and the required administration route. This work gives an overview on the effect
      of both the type and amount of lipids and surfactants used in the manufacture of
      lipid based nanocarriers on their behavior and characteristics. CONCLUSION:
      Recent studies revealed that the properties of the final product including;
      particle size, homogeneity, drug loading capacity, zeta potential, drug release
      profile, stability, permeability, pharmacokinetic properties, crystallinity and
      cytotoxicity, may be significantly influenced not only by the type but also the
      amount of the lipids and/or surfactants included in the formulation of the lipid
      based nanocarriers.

PMID- 29189139
TI  - Lipid nanoparticles for the delivery of active natural medicines.
AB  - BACKGROUND: Thousands of bioactive compounds are identified and isolated from the
      medicinal plants every year, of which many possess significant health benefits.
      However, the overwhelming majority of entities suffer from poor water solubility
      and membrane permeability that impedes them approaching the clinical stage.
      METHODS: Lipid nanoparticles have shown to be a versatile platform for advanced
      delivery of various therapeuticals, including the oral, topical and systemic
      routes. Lipid nanoparticles are able to significantly improve the oral
      bioavailability, pharmacokinetic profile, skin permeability, and ocular residence
      time of drugs, demonstrating considerable potential in pharmaceutical or medical
      practice. RESULTS: This article profoundly reviews important applications of
      lipid nanoparticles in active natural medicines. Special concerns focus on solid
      lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for their
      training in the oral, intravenous, percutaneous and ocular drug delivery.
      CONCLUSION: The survey shows that lipid nanoparticles are promising vehicles for
      the delivery of various natural actives and may address some intractable problems
      associated with delivery thereof.

PMID- 29189138
TI  - Intranasal lipid nanoparticles for the treatment of neurodegenerative diseases.
AB  - BACKGROUND: Current treatments for neurodegenerative diseases are challenging,
      due to the absence of full effective medicines. One of the major problems
      associated to these is the occurrence of non-targeting events, which leads to
      adverse effects and requires frequent dose administration. METHODS: Researches
      have been performed to develop new drug delivery systems administrated by
      alternative routes. For example, the direct nose-to-brain delivery of drugs by
      means of lipid nanoparticles, such as solid lipid nanoparticles (SLN) and
      nanostructured lipid carriers (NLC), have been showing promising results.
      RESULTS: Among the advantages of intranasal administration is the avoidance of
      passing the blood-brain barrier (BBB) to reach the central nervous system (CNS),
      allowing the direct delivery of drugs to the brain by a non-invasive way,
      minimizing systemic exposure and prolonging residence time. This review article
      discusses the advantages of using SLN and NLC for direct nose-to-brain drug
      delivery. A brief reference to other lipid-based carriers (liposomes,
      nanoemulsions and microemulsions) is also provided. CONCLUSION: The benefits of
      using SLN and NLC for improve nasal drug delivery have been demonstrated by in
      vitro, ex vivo and in vivo experiments. However, more in vivo animal studies are
      needed for advance to human clinical trials and reach clinics.

PMID- 29189140
TI  - Polyphenols Effect on Circulating Lipids and Lipoproteins: From Biochemistry to
      Clinical Evidence.
AB  - BACKGROUND: Polyphenols are a family of natural antioxidants that in recent years
      have been studied and tested for their potential benefits towards cardiovascular
      diseases. OBJECTIVE: The aim of this review is to focus the attention on the
      presumed lipid-lowering and atheroprotective effects of polyphenols, administered
      either as individual molecules (nutritional supplements) and as functional foods,
      on the basis of the evidence coming from randomized controlled trials (RCTs) and
      their meta-analyses. METHOD: A search strategy was conducted to identify studies
      in PubMed (January 1980 to September 2016); in particular, we have included human
      clinical trials, reviews and meta-analyses when they offered suitable insights
      and elucidations regarding the action of polyphenols on lipid profile and
      cardiovascular disease risk. RESULTS: Literature data on polyphenols suggest that
      they potentially could exert an effect on lipid profile, especially by reducing
      the oxidation of LDL-C. Polyphenols from cocoa, grape, green tea, berries and soy
      are the ones that have shown more clinically relevant effect. However,
      quantitative data on cholesterol reduction are still unclear and often
      conflicting. CONCLUSION: Polyphenols, if taken in adequate dosages, can exert in
      some cases a positive effect on the prevention of cardiovascular risk and lipid
      oxidation, despite an unclear effect on lipid levels.

PMID- 29189141
TI  - Prediction of Tissue to Plasma Concentration Ratios of Drugs in the Rat from
      Experimentally Estimated Volume of Distribution: Application of Allometry.
AB  - BACKGROUND: In Physiologically Based Pharmacokinetic (PBPK) models, the most
      important input parameter is tissue-to-plasma partition coefficient (Kp). Over
      the years, several empirical methods have been developed to predict Kp in
      animals. OBJECTIVES: The objective of this study was to propose two allometric
      methods to predict Kp from experimentally determined in vivo volume of
      distribution at steady state (Vss). METHOD: In one method, Vss was allometrically
      predicted (using a fixed exponent 1.0 or 0.8) in a given tissue of the rat and
      then Kp was predicted for that tissue. In another method, an allometric plot (Kp
      versus Vss) was developed to predict Kp in a tissue of the rat. In total, Kp
      values were predicted for 46 drugs and 338 tissues. The predicted Kp values by
      the proposed two methods were compared with the experimentally determined Kp
      values as well as empirically predicted Kp values by other investigators.
      RESULTS: Comparison of the predicted Kp values by the two proposed methods with
      experimentally determined Kp values indicated that 67-72% of the predicted Kp
      values were within two-fold prediction error. The predictive power or accuracy of
      method 1 (when taken all tissues and all classes of drugs into account) was 19%,
      35%, 14%, 35%, 14%, and 13% better than the methods proposed by Arundel,
      Berezhkovskiy, Jansson et al., Poulin et al., Poulin- Theil, and Rodgers et al.
      respectively. CONCLUSION: The proposed two allometric methods are slightly more
      accurate than other empirical methods in their predictive performance for the
      prediction of tissue Kp values for acidic, weak bases and neutral drugs.

PMID- 29189142
TI  - Interpretation of Cannabis Findings in the Hair of Very Young Children: Mission
      Impossible.
AB  - BACKGROUND: Hair has been suggested since the middle of the 90's to be a suitable
      matrix to document repetitive exposure to cannabis. Because it is possible to
      detect Delta9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD)
      in cannabis smoke, the identification of the metabolite, 11-nor-Delta9
      tetrahydrocannabinol carboxylic acid (THC-COOH) has been considered to allow the
      discrimination of active use. OBJECTIVE: Although the identification of an active
      compound in a child's hair shows contamination of the local environment, it is a
      challenge to discriminate between hair incorporation after ingestion or
      inhalation and environmental external deposition from dust, smoke, or even
      contaminated surfaces by hand contact. However, it is particularly important in
      case of children to correctly interpret the data, particularly for a realistic
      assessment of the health risk. We present here a series of hair tests for
      cannabis where the interpretation was almost impossible to establish. METHOD:
      Hair specimens were collected during the autopsy of the 12 children, aged 2 to 24
      months, either deceased from shaken baby syndrome (SBS, n=4), mechanic asphyxia
      (MA, n=1) or sudden infant death (SID, n=7) during January 2015 to April 2017.
      After decontamination, the hair specimens were tested for THC, CBN and CBD and
      THC-COOH. The whole length of hair was submitted to analysis. RESULTS: The amount
      of hair from children can be as low as 8 mg. This may affect the limit of
      quantitation of all drugs, but particularly THC-COOH. Eight from twelve hair
      tests were positive for cannabis markers, i.e. THC (39 to 1890 pg/mg, n=8), CBN
      (< 5 to 1300 pg/mg n=8), CBD (10 to 2300 pg/mg, n=8) and THC-COOH (not detected
      to < 0.5 pg/mg, n=5). In 4 cases from 8 positive findings, it was not possible to
      test for THC-COOH (not enough material). CONCLUSION: Establishing a window of
      detection when testing for drugs in young children is a very complicated task.
      Hair from children is finer and more porous in comparison with adult (the risk of
      contamination from sweat and environmental smoke is higher than in adults). The
      final interpretation of cannabinoid findings in the children's hair is very
      complicated as this can result from in utero exposure (although none of the
      mother admitted cannabis use during pregnancy), oral cannabis administration by
      the parents to achieve sedation, close contact to cannabis consumers (hands,
      bedding, dishes) and inhalation of side-stream smoke. Over-interpreting cannabis
      findings in hair can have very serious legal implication in child protection
      cases. Practicing scientists have the responsibility to inform the child
      protection authorities, courts, etc. about these limitations.

PMID- 29189143
TI  - Retrospective Demonstration of 25I-NBOMe Acute Poisoning Using Hair Analysis.
AB  - BACKGROUND: The abuse of new psychoactive substances or NPS has been dramatically
      increasing all around the world since the last half of the year 2000 and has
      become a serious public health problem. NPS are a challenge for the worldwide
      forensic community due to the difficulties to accurately document the cases. The
      N-benzylmethoxy (NBOMe) group is a new class of hallucinogenic designer drugs and
      has gained importance in recent years. 25I-NBOMe (2-(4-iodo-2,5-dimethoxyphenyl)
      N-[(2-methoxyphenyl)- methyl]ethanamine) is an analog of the 2C series of
      psychedelic phenethylamine drugs that contain an N-methoxybenzyl substituent,
      which significantly affects their pharmacological activities. It is a potent
      agonist of 5-HTA receptors and a severe hallucinogenic drug, with numerous
      irreversible psychedelic effects which can last from 5 to 10 hours. It is
      consumed most often in the form of drops or blotters by the transmucosal,
      sublingual or intranasal routes. The active dosage is very low, supposed to be
      less than 100 ug. The literature is poor in reporting cases where 25I-NBOMe was
      identified. Only very few clinical cases of over dosages were published,
      suggesting a low prevalence of this compound. METHODS: We present a retrospective
      demonstration of 25I-NBOMe acute poisoning with dramatic outcome, using hair
      analysis. Two hair strands, measuring 9.5 cm, were collected 6.5 months after
      drug consumption during a forensic clinical evaluation of brain dysfunctions
      after cardiorespiratory arrest and were analyzed by ultra-high performance liquid
      chromatography system coupled to a tandem mass spectrometry (UPLC-MS/MS) and
      using two specific transitions: m/z 428.1 > 121.2 (quantification) and 428.1 >
      90.6 (confirmation). Hair strands were segmented to determine the historic
      pattern of drug use and differentiate a single exposure from a chronic exposure.
      The hair test result for 25I-NBOMe was the following: not detected (0-2 cm), not
      detected (2-4 cm), 1.0 pg/mg (4-6 cm), 4.9 pg/mg (6-8 cm) and not detected (8-9.5
      cm). RESULT: The result of the segment 6-8 cm coincides with the date of
      consumption (calculated with a hair growth rate at 1 cm/month) and the low
      concentration detected in the segment 4-6 cm probably corresponds to the
      contribution of dormant hair. The toxicological significance of the measured
      concentrations is difficult to determine because this is the first case dealing
      with hair analysis for 25I-NBOMe. CONCLUSION: The use of hair analysis for NPS is
      still at the initial stages. In particular, little is known about the
      incorporation into the keratin matrix after intake and the correlation between
      dosage frequency of use, and hair concentrations. Under these circumstances, NPS
      hair analysis should be cautiously interpreted by experienced forensic
      toxicologist.

PMID- 29189144
TI  - Therapeutic Use of Delta9-THC and Cannabidiol: Evaluation of a New Extraction
      Procedure for the Preparation of Cannabis-based Olive Oil.
AB  - BACKGROUND: Since 2013 Cannabis-based preparations, containing the two main
      cannabinoids of interest, Delta9-tetrahydrocannabinol (THC), and cannabidiol
      (CBD), can be used for therapeutic purposes, such as palliative care,
      neurodegenerative disorder treatment and other therapies. The preparations may
      consist of a drug partition in sachets, capsules or through the extraction in
      certified olive oil. OBJECTIVE: The aims of the study were: a) to develop and
      validate a new liquid chromatographictandem mass spectrometric (LC-MS/MS) method
      for the identification and quantification of THC and CBD in olive oil; b) to
      evaluate the extraction efficiency and reproducibility of a new commercial
      extractor on the market. METHODS: The olive oil was simply diluted three
      consecutive times, using organic solvents with increasing polarity index (n
      hexane -> isopropanol -> methanol). The sample was then directly injected into LC
      MS/MS system, operating in Multiple Reaction Monitoring Mode, in positive
      polarization. The method was then fully validated. RESULTS: The method assessed
      to be linear over the range 0.1-10 ng/uL for both THC and CBD. Imprecision and
      accuracy were within 12.2% and 16.9% respectively; matrix effects proved to be
      negligible; THC concentration in oil is stable up to two months at room
      temperature, whenever kept in the dark. CBD provided a degradation of 30% within
      ten weeks. The method was then applied to olive oil after sample preparation, in
      order to evaluate the efficiency of extraction of a new generation instrument.
      Temperature of extraction is the most relevant factor to be optimized. Indeed, a
      difference of 2 degrees C (from 94.5 degrees C to 96.5 degrees C, the highest
      temperature reached in the experiments) of the heating phase, increases the
      percentage of extraction from 54.2% to 64.0% for THC and from 58.2% to 67.0% for
      CBD. The amount of THC acid and CBD acid that are decarboxylated during the
      procedure must be check out in the future. CONCLUSION: The developed method was
      simple and fast. The extraction procedure proved to be highly reproducible and
      applicable routinely to cannabis preparations.

PMID- 29189145
TI  - Transforming Growth Factor-Beta Family: Advances in Vascular Function and
      Signaling.
AB  - This review includes a comprehensive, but succinct, summary on the essentials of
      TGF- beta structure, family members, receptors, and intracellular mediators. Also
      provided is a select list of original publications that report novel roles and
      facets of TGF-beta in vascular function and signaling in the contexts of health
      and disease.

PMID- 29189146
TI  - Transforming Growth Factor Beta Type I Role in Neurodegeneration: Implications
      for Alzheimer's Disease.
AB  - Alzheimer's disease is a neurodegenerative condition affecting millions of people
      worldwide. Alzheimer's symptoms include memory loss and cognitive decline.
      Pathologically, the hallmarks of Alzheimer's are the presence of Amyloid beta
      plaques, neurofibrillary tangles, and neuronal loss. Unfortunately, no cure is
      presently available and current treatments are only symptomatic. Transforming
      growth factor beta type I (TGF-beta1) is a trophic factor involved in neuronal
      development and synaptic plasticity. Impairment of TGF-beta1 signaling is
      associated with exacerbated Abeta deposition and neurofibrillary tangle
      formation, which increases neurodegeneration. Aging and chronic inflammation
      reduce the canonical TGF-beta1/Smad signaling, facilitating cytotoxic activation
      of microglia and microgliamediated neurodegeneration This review gathers together
      evidence for a neuroprotective role of TGF-beta in Alzheimer's disease. Restoring
      TGF-beta1 signaling impairment may be a new pharmacological strategy Alzheimer's
      treatment.

PMID- 29189147
TI  - Disrupting Acetyl-lysine Interactions: Recent Advance in the Development of BET
      Inhibitors.
AB  - BACKGROUND: Histone acetylation is an essential approach of post-translational
      modification (PTM) and a significant component of epigenetic regulation that is
      mediated by Bromodomainscontaining protein (BRDs). In recent years, many
      researchers have found that a variety of malignancy, inflammatory and other
      diseases occurrences and developments are associated with BRD4 expression
      disorders or dysfunction. Meanwhile, many inhibitors of the extra-terminal (BET)
      family have been reported in many papers. OBJECTIVE: This review summarized those
      newly found BET inhibitors, their mechanism of action and bioactivity. Secondly,
      those compounds were mainly classified based on their structures and their
      structure-activity relationship information was discussed. Beyond that, every
      compound's design strategy was pointed out. RESULTS AND CONCLUSION: Herein, the
      recent advances reported were reviewed for discovering more excellent small
      molecule inhibitors. Currently, in addition to compound 4, compounds 7, 22 and
      90, have also been into the clinical trial stage. In the view of the outstanding
      performance of BET inhibitors in anti-tumor, anti-inflammatory and anti-drug
      resistance, we believe that more and more BET inhibitors will become the new
      epigenetic therapy for cancer, inflammation and autoimmune disease in clinical
      practice in the near future.

PMID- 29189148
TI  - Identification of Novel Ligands for Therapeutic Lipopeptides: Daptomycin,
      Surfactin and Polymyxin.
AB  - BACKGROUND: Due to increase in antibiotic-resistance among pathogens, there is a
      need for potent and safe drugs. An alternative to antibiotics is lipopeptides
      which are produced as a secondary metabolite by many microorganisms. They exhibit
      broad-spectrum activities against pathogens along with anticancer properties.
      Among various lipopeptides produced by microorganisms, daptomycin, surfactin, and
      polymyxin have gained popularity as medicines but their mechanism of action is
      not described properly. In silico drug design of these lipopeptides becomes a
      challenge due to their complex structures. In order to initiate a physiological
      response, specific agonists (ligands) of their receptor (lipopeptide) must be
      identified. OBJECTIVE: The objective of this study was molecular docking of three
      lipopeptides, daptomycin, surfactin and polymyxin, with their ligands as a means
      of drug design. METHOD: Schrodinger software was used for molecular docking of
      lipopeptides with their corresponding ligands whereas the ligand search was done
      using RCSB. Once the ligands were identified, they were docked with their
      corresponding lipopeptide. Docking score and glide energy were used as the
      parameters to test docking. RESULTS: All four of the identified ligands were
      found to dock with daptomycin, whereas for both surfactin and polymyxin one out
      of two ligands docked with the lipopeptides. CONCLUSION: The knowledge of the
      docking sites and docking characteristics of the lipopeptide mentioned in the
      paper with the ligands can provide advantages of high speed and reliability,
      reduced costs on chemicals and experiments and the ethical issues concerned with
      the use of animal models for screening of drug toxicity.

PMID- 29189149
TI  - Theranostic Aspects: Treatment of Cancer by Nanotechnology.
AB  - Theranostic agents or theranostic imaging as its name suggests is a combination
      of two terms-'diagnosis' & 'therapy'. Efforts are being made to combine both the
      terms into clinical formulations. This theranostic imaging is found to be very
      much significant to complex diseases like cancer and proliferative tumors
      especially because accurate photocopy for every tumor can be obtained by genomic
      and proteomic profiling and using such informations in theranostic agents can be
      constructed or modeled in such a way that it is specific in its action and
      selective towards the cancer cells only, without causing any adverse effects on
      the normal tissue cells. By means of nanoplatforms, we can conveniently deliver
      cancer cell specific targeting ligand or peptide inside the human body. Primary
      delivery approach comprises of nanoparticles, liposomes, dendrimers, prodrugs,
      polymersomes, carbon nanotubes and polymeric micelles. Theranostic agents, i.e.,
      therapeutic and diagnostic agents can be physically bound or else they can be
      bound with polymers which are exclusively designed and this together forms
      nanocarriers. Hence, the review highlights the advances of nanotechnology that
      has given us a platform for cancer detection and treatment.

PMID- 29189150
TI  - Natural Bioactive New Withanolides.
AB  - Withanolides are a group of highly oxygenated steroids derived from a C28
      ergostane skeleton, and have attracted significant scientific interest due to
      their complex structural features and multiple bioactivities. More than 170 new
      natural withanolides were isolated and identified in the last 5 years. This
      review provides a comprehensive summary of the structural, biological and
      pharmacological activities and distribution of these new compounds.

PMID- 29189151
TI  - Assorted applications of N-substituted-2,4-thiazolidinediones in various
      pathological conditions.
AB  - Thiazolidine-2,4-dione (TZD), one of the most frequently encountered heterocyclic
      ring which has been implicated in design and synthesis of entities for various
      pathogenic conditions including cancer. Since its discoveryvarious substitutions
      at 5th position has been carried out and reviewed. Various substitutions at 5th
      position has led to generation of glitazones, whose target peroxisome
      proliferating activated receptor gamma (PPARgamma) was found decade after their
      discovery.Acidichydrogen (-NH) of TZD is prime pharmacophoric requirement for
      activation of PPARgamma. However, advanced in silico techniques have helped to
      design compounds bearing substitutions at both methylene and -NH group of TZD,
      targeting range of enzymes involved in various pathological conditions
      viz.,diabetes, hyperlipidemia, infectious disease, inflammation and cancer. The
      promising activities shown by methylene and N-substituted TZDsin above mentioned
      therapeutic areas, prompted us to collate the information which would help
      researchers to alter the structure of existing ligands and to design new TZD
      derivatives with better safety and efficacy profiles.

PMID- 29189152
TI  - The Progress of Gene Therapy for Leber's Optic Hereditary Neuropathy.
AB  - INTRODUCTION: Leber's Optic Hereditary Neuropathy (LHON) is a common cause of
      teenaged blindness in both eyes for which there is currently no effective
      treatment. In 1871, the German ophthalmologist Theodor Leber was the first to
      describe the clinical characteristics of his namesake disease, and through
      unremitting efforts over the past 100 years, researchers have continued to
      increase their understanding of LHON. In recent years, using gene therapy,
      several groups have obtained breakthroughs in the treatment of the disease.
      CONCLUSION: In this article, we will review the challenging journey that
      researchers faced towards our current understanding of LHON, and describe the
      transition of gene therapy research for LHON from the bench to bedside.

PMID- 29189154
TI  - Brain Targeted Intranasal Zaleplon Nano-emulsion: In-Vitro Characterization and
      Assessment of Gamma Aminobutyric Acid Levels in Rabbits' Brain and Plasma at Low
      and High Doses.
AB  - BACKGROUND: Zaleplon is a pyrazolopyrimidin derivative hypnotic drug indicated
      for the short-term management of insomnia. Zaleplon belongs to Class II drugs,
      according to the biopharmaceutical classification system (BCS), showing poor
      solubility and high permeability. It undergoes extensive first-pass hepatic
      metabolism after oral absorption, with only 30% of Zaleplon being systemically
      available. It is available in tablet form which is unable to overcome the
      previous problems. OBJECTIVE: The aim of this study is to enhance solubility and
      bioavailability via utilizing nanotechnology in the formulation of intranasal
      Zaleplon nano-emulsion (ZP-NE) to bypass the barriers and deliver an effective
      therapy to the brain. METHOD: Screening studies were carried out wherein the
      solubility of zaleplon in various oils, surfactants( S) and co-surfactants(CoS)
      were estimated. Pseudo-ternary phase diagrams were constructed and various nano
      emulsion formulations were prepared. These formulations were subjected to
      thermodynamic stability, in-vitro characterization, histopathological studies and
      assessment of the gamma aminobutyric acid (GABA) level in plasma and brain in
      rabbits compared to the market product (Sleep aid(r)). RESULTS: Stable NEs were
      successfully developed with a particle size range of 44.6+/-3.4 to 136.9+/-1.6
      nm. CONCLUSION: A NE composed of 10% Miglyol(r) 812, 40% Cremophor(r) RH40
      40%Transcutol(r) HP and 10% water successfully enhanced the bioavailability and
      brain targeting in the rabbits, showing a three to four folds increase than the
      marketed product.

PMID- 29189153
TI  - Antiviral Effects of Saffron and its Major Ingredients.
AB  - BACKGROUND: The lack of an effective vaccine against viral infections, toxicity
      of the synthetic anti-viral drugs and the generation of resistant viral strains
      led to discover novel inhibitors. Recently, saffron and its compounds were used
      to treat different pathological conditions. METHOD: In this study, we tested the
      anti-HSV-1 and anti-HIV-1 activities of Iranian saffron extract and its major
      ingredients including crocin and picrocrocin as well as cytotoxicity in vitro.
      The data showed that the aqueous saffron extract was not active against HIV-1 and
      HSV-1 virions at certain doses (i.e., a mild activity), but crocin and
      picrocrocin indicated significant anti-HSV-1 and also anti-HIV-1 activities.
      Crocin inhibited the HSV replication at before and after entry of virions into
      Vero cells. Indeed, crocin carotenoid suppressed HSV penetration in the target
      cells as well as disturbed virus replication after entry into the cells.
      Picrocrocin was also effective for inhibiting virus entry and also its
      replication. RESULTS: This monoterpen aldehyde showed higher anti-HSV effects
      after virus penetrating in the cells. Generally, these sugar-containing compounds
      extracted from saffron showed to be effective antiherpetic drug candidates.
      CONCLUSION: The recent study is the first report suggesting antiviral activities
      for saffron extract and its major ingredients. Crocin and picrocrocin could be a
      promising anti-HSV and anti-HIV agent for herbal therapy against viral
      infections.

PMID- 29189155
TI  - Fabrication and Characterization of Timolol Maleate and Brinzolamide Loaded
      Nanostructured Lipid Carrier System for Ocular Drug Delivery.
AB  - BACKGROUND: The combination of timolol maleate (TM) and brinzolamide (BRZ) has
      potential therapeutic prospects for treating glaucoma. However, the conventional
      formulation of TM and BRZ exhibits sub optimal therapeutic effects attributable
      to the poor ocular bioavailability of these drugs. OBJECTIVE: Therefore, the aim
      of the present study was to design and evaluate TM and BRZ loaded nanostructured
      lipid carrier (NLC) to enhance the bioavailabilities, permeation and precorneal
      residence time of these drugs that would result in efficacious treatment of
      glaucoma. METHODS: In this study, combination of drugs with different
      characteristic properties was loaded in NLC. The dual drugs loaded NLC was
      prepared by melt emulsification technique and evaluated for characteristic
      properties such as particle size (PS), polydispersity index (PDI), entrapment
      efficiency (EE) and drug loading (DL), in vitro drug release and ex vivo drug
      penetration studies. RESULTS: The PS and PDI of optimized NLC formulation were
      found to be 110.36 +/-0.47 nm and 0.24 +/- 0.00 respectively. The EE and DL of
      optimized NLC formulation were found to be 77.12 +/- 0.64 % and 0.360 +/- 0.01 %
      for TM respectively; whereas, 70.73+/-0.64 % and 0.71 +/- 0.02 %for BRZ
      respectively. In vitro drug release studies showed a comparable initial rapid
      release of around 34 +/- 2.90 % for TM and 38 +/- 3.10 % for BRZ in the first 5 h
      followed by sustained drug release around 72.29 +/- 5.90 % for TM and 70.08 +/-
      6.40 % for BRZ until last 24 h. Ex vivo drug penetration studies showed about
      33.47 +/- 2.80 % of TM and 36.20 +/- 2.80 % of BRZ permeated in the first 5 h
      followed by 72.30 +/- 6.40% of TM and 67.69 +/- 6.500 % of BRZ until 24 h. There
      was remarkable enhancement in the release pattern and permeation of both the
      drugs from NLC as compared to that from their suspension. CONCLUSION: With
      dextrous optimization of dose and excipients concentration, the dual drugs with
      different characteristic properties can be successfully loaded in NLC
      formulation.

PMID- 29189156
TI  - Post-stroke Constraint-induced Movement Therapy Increases Functional Recovery,
      Angiogenesis, and Neurogenesis with Enhanced Expression of HIF-1alpha and VEGF.
AB  - BACKGROUND: Constraint-Induced Movement Therapy (CIMT) is one efficient approach
      to improve functional recovery after ischemic stroke. The underlying molecular
      mechanism remains unclear. In the current study, we investigated the effects of
      CIMT on angiogenesis and neurogenesis. To start linking our findings to molecular
      mediators, we further examined the expression of Hypoxia-Inducible Factor-1alpha
      (HIF-1alpha), Factor Inhibiting HIF-1 (FIH-1) and Vascular Endothelial Growth
      Factor (VEGF). METHODS: Rats were randomly assigned into three groups: a Middle
      Cerebral Artery Occlusion group (MCAO), a therapeutic group (CIMT+MCAO), and a
      sham middle cerebral artery occlusion group (Sham). Seven days after surgery, a
      plaster cast was placed around the unimpaired upper limb of the rats in the
      CIMT+MCAO group for 14 days. CIMT was performed on a horizontal ladder.
      Neurobehavioral consequences were evaluated using the Open-Field Test (OFT) and
      the Foot-Fault Test (FFT). The number of new neurons, the length of vessels as
      well as the expression of HIF-1alpha, FIH-1, and VEGF were examined before and
      after 14 days of CIMT. RESULTS: The CIMT+MCAO group showed a significant increase
      in the total length of microvessels and increased number of Bromodeoxyuridine+
      (BrdU+)/NeuN+ double-labeled cells. These changes were correlated with an
      increase in HIF-1alpha and VEGF expressions and a decrease in FIH-1expression.
      FFT showed that the CIMT+MCAO group exhibited marked improvement in
      neurobehavioral outcome when compared to the MCAO group. Adverse effects on total
      activities or anxiety were not observed using open field analysis. CONCLUSION:
      CIMT-induced neuroprotection and functional recovery following cerebral ischemia
      were possibly mediated by an increase in endogenous HIF-1alpha and VEGF
      expression with subsequent neurogenesis and angiogenesis.

PMID- 29189157
TI  - Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects.
AB  - Numerous authors have provided evidence regarding the beneficial effects of
      phenolic acids and their derivatives against Alzheimer's disease (AD). In this
      review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE)
      and butyrylcholinesterase (BChE) is discussed, including the structure-activity
      relationship. In addition, the inhibitory effect of phenolic acids on the
      formation of amyloid beta-peptide (Abeta) fibrils is presented. We also cover the
      in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of
      the cognitive enhancement.

PMID- 29189158
TI  - Cancer Targeted Therapy Strategy: The Pathologist's Perspectives.
AB  - The effectiveness of new personalized treatment procedures in oncology is based
      on the fact that certain tumors exhibit specific molecular features. More in
      detail, neoplastic tissues of patients should display a specific biomarker, most
      often a specific genetic alteration and/or under/overexpression of a definite
      protein, that could be the target of its respective drug. Immunohistochemical and
      molecular analyses, which usually include examination of nucleic acids from
      either tissues or fluids, are common tests to define the status of a tumor. This
      review focuses on the pathologist's role in carefully controlling pre- analytic
      procedures and standard operating procedures that are a crucial prerequisite to
      reach reliable and reproducible results. Six paradigmatic applications of
      targeted therapy, for which pathological diagnosis plays a fundamental role, are
      summarized. Traditional and next-generation sequencing are also addressed from
      the pathologist's perspective as well as the importance pathologists have in this
      shift to more accurate definition of disease risk and prognostication of therapy
      response in the personalized medicine era.

PMID- 29189159
TI  - Oncorine, the World First Oncolytic Virus Medicine and its Update in China.
AB  - The oncolytic viruses now hold a promise of new therapeutic strategy for cancer.
      Its concept has inspired a wave of commercial research and development activities
      for the products of this category in China since 1998. The first commercialized
      oncolytic virus product in the world, Oncorine (H101), developed by Shanghai
      Sunway Biotech Co., Ltd since 1999, was approved by Chinese SFDA in November,
      2005 for nasopharyngeal carcinoma in combination with chemotherapy after the
      phase III clinical trial, and finally acquired GMP certificate in August, 2006.
      This review introduces how Oncorine was successfully developed in China, and how
      the Chinese market responded after it was launched into the market in 2006.

PMID- 29189160
TI  - Role of Glioma-associated GLI1 Oncogene in Carcinogenesis and Cancertargeted
      Therapy.
AB  - Glioma-associated oncogenes (GLIs) are zinc finger protein family members and
      downstream regulatory factors of the classic Hedgehog (Hh) signaling pathway. GLI
      proteins influence the growth and development of organisms and aid in tissue
      repair. However, aberrant expression of the GLI family member GLI1 promotes
      carcinogenesis by inducing epithelial-mesenchymal transition (EMT), angiogenesis,
      and other signaling pathways. Overexpression of GLI1 is thought to be an
      indicator of poor prognosis as well as a potential therapeutic target for
      cancers. GLI inhibitors such as zerumbone, GANT61, resveratrol, and cyclopamine
      depress the Hh pathway in vitro and in vivo cancer research, and other non
      canonical pathways may also activate expression of GLI1. Here, we summarize GLI
      function in carcinogenesis and cancer-targeted therapy.

PMID- 29189161
TI  - Toxicology of Trastuzumab: An Insight into Mechanisms of Cardiotoxicity.
AB  - Trastuzumab is a humanized monoclonal antibody that is approved for the treatment
      of breast and gastric malignancies. Although it has shown promise as a
      biotherapeutic, its cardiotoxicity remains a major concern. Genotoxic anticancer
      anthracyclines such as doxorubicin and epirubicin are also known for their
      cardiotoxic effects. However, trastuzumab and anthracyclines are suggested to
      mediate cardiotoxicity via different pathways. The available lines of evidence
      suggest that trastuzumab can exacerbate the cardiotoxic effects of anthracyclines
      and thus, prior exposure to anthracyclines is a regarded as one of the risk
      factors for trastuzumab-induced cardiotoxcity. Although it is generally believed
      that the trastuzumab-induced cardiotoxic effects are reversible, various
      preclinical studies have revealed its apoptotic effects on cardiomyocytes. Thus,
      the issue of the reversibility of its cardiotoxic effects remains to be fully
      resolved. This article discusses various mechanisms that have been proposed for
      the cardiotoxic effects of trastuzumab and the potential risk factors that can
      lead to cardiotoxicity. The recently approved anti-HER2 monoclonal antibodies
      including pertuzumab and ado-trastuzumab (T-DM1) are also discussed.

PMID- 29189162
TI  - Tunneling Nanotubes: A Versatile Target for Cancer Therapy.
AB  - Currently Cancer is the leading cause of death worldwide. Malignancy or cancer is
      a class of diseases characterized by uncontrolled cell growth that eventually
      invade other tissues and develop secondary malignant growth at other sites by
      metastasis. Intercellular communication plays a major role in cancer,
      particularly in the process of cell proliferation and coordination which in turn
      leads to tumor invasion, metastasis and development of resistance to therapy.
      Cells communicate among themselves in a variety of ways, namely: i) via gap
      junctions with adjacent cells; ii) via exosomes with nearby cells; and iii) via
      chemical messengers with distant cells. Besides, cell - cell connection by
      tunneling nanotubes (TnTs) is recently gaining importance where intercellular
      components are transferred between cells. In general cell organelles like Golgi
      vesicle and mitochondria; and biomolecules like nucleic acids and proteins are
      transferred through these TnTs. These TnTs are long cytoplasmic extensions made
      up of actin that function as intercellular bridge and connect a wide variety of
      cell types. Malignant cells form TnTs with either other malignant cells or cells
      of the surrounding tumor matrix. These TnTs help in the process of initiation of
      tumor formation, its organization and propagation. The current review focuses on
      the role of TnTs mediated cell - cell signaling in cancer micro-environment.
      Drugs that inhibit TnT-formation such as metformin and everolimus can be targeted
      towards TnTs in the management of cancer growth, proliferation, tumor invasion
      and metastasis.

PMID- 29189164
TI  - Alzheimer: A Decade of Drug Design. Why Molecular Topology can be an Extra Edge?
AB  - BACKGROUND: The last decade was characterized by a growing awareness about the
      severity of dementia in the field of age-related and no age-related diseases and
      about the importance to invest resources in the research of new, effective
      treatments. Among the dementias, Alzheimer's plays a substantial role because of
      its extremely high incidence and fatality. Several pharmacological strategies
      have been tried but still now, Alzheimer keeps being an untreatable disease. In
      literature, the number of QSAR related drug design attempts about new treatments
      for Alzheimer is huge, but only few results can be considered noteworthy.
      Providing a detailed analysis of the actual situation and reporting the most
      notable results in the field of drug design and discovery, the current review
      focuses on the potential of molecular topology as a reliable tool in finding new
      anti-Alzheimer lead compounds. METHODS: Published works on QSAR applied to the
      search of anti-Alzheimer's drugs during the last 10 years has been tracked. 2D
      and 3D-QSAR, HQSAR, topological indexes, etc. have been analyzed, as well as
      different mechanisms of action, such as MAO, AchE, etc. An example of topological
      indexes' application to the search of potential anti-Alzheimer drugs is reported.
      RESULTS: Results show that QSAR methods during the last decade represented an
      excellent approach to the search of new effective drugs against Alzheimer's. In
      particular, QSAR based on molecular topology allows the establishment of a direct
      structure-property link that results in the identification of new hits and leads.
      CONCLUSION: Molecular topology is a powerful tool for the discovery of new anti
      Alzheimer drugs covering simultaneously different mechanisms of action, what may
      help to find a definitive cure for the disease.

PMID- 29189163
TI  - Alpha-synuclein, Proteotoxicity and Parkinson's Disease: Search for
      Neuroprotective Therapy.
AB  - BACKGROUND: There is a growing body of evidence in animal and cell based models
      of Parkinson's disease (PD) to suggest that overexpression and / or abnormal
      accumulation and aggregation of alpha-synuclein can trigger neuronal death. This
      important role of alpha-synuclein in PD pathogenesis is supported by the fact
      that duplication, triplication and mutations of alpha-synuclein gene cause
      familial forms of PD. METHODS: A review of literature was performed by searching
      PubMed and Google Scholar for relevant articles highlighting the pathogenic role
      of alpha-synuclein and the potential therapeutic implications of targeting
      various pathways related to this protein. RESULTS: The overexpression and
      accumulation of alpha-synuclein within neurons may involve both transcriptional
      and post-transcriptional mechanisms including a decreased degradation of the
      protein through proteasomal or autophagic processes. The mechanisms of monomeric
      alpha-synuclein aggregating to oligomers and fibrils have been investigated
      intensively, but it is still not certain which form of this natively unfolded
      protein is responsible for toxicity. Likewise the proteotoxic pathways induced by
      alpha- synuclein leading to neuronal death are not elucidated completely but
      mitochondrial dysfunction, endoplasmic reticulum (ER) stress and altered ER-golgi
      transport may play crucial roles in this process. At the molecular level, the
      ability of alpha-synuclein to form pores in biomembranes or to interact with
      specific proteins of the cell organelles and the cytosol could be determining
      factors in the toxicity of this protein. CONCLUSION: Despite many limitations in
      our present knowledge of physiological and pathological functions of alpha
      synuclein, it appears that this protein may be a target for the development of
      neuroprotective drugs against PD. This review has discussed many such potential
      drugs which prevent the expression, accumulation and aggregation of alpha
      synuclein or its interactions with mitochondria or ER and thereby effectively
      abolish alpha-synuclein mediated toxicity in different experimental models.

PMID- 29189165
TI  - Childhood Medulloblastoma: Current Therapies, Emerging Molecular Landscape and
      Newer Therapeutic Insights.
AB  - BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children,
      currently treated uniformly based on histopathology and clinico-radiological risk
      stratification leading to unpredictable relapses and therapeutic failures.
      Identification of molecular subgroups have thrown light on the reasons for these
      and now reveals clues to profile molecularly based personalized therapy against
      these tumors. METHODS: Research and online contents were evaluated for pediatric
      medulloblastoma which included latest information on the molecular subgroups and
      their clinical relevance and update on efforts to translate them into clinics.
      RESULTS: Scientific endeavors over the last decade have clearly identified four
      molecular variants (WNT, SHH, Group 3, and Group 4) and their demographic,
      genomic, and epigenetic profile. Latest revelations include significant
      heterogeneity within these subgroups and 12 different subtypes of MB are now
      identified with disparate outcomes and biology. These findings have important
      implications for stratification and profiling future clinical trials against
      these formidable tumors. CONCLUSION: With the continued outpouring of
      genomic/epigenomic data of these molecular subgroups and evolution of further
      subtypes in each subgroup, the challenge lies in comprehensive evaluation of
      these informations. Current and future endeavors are now needed to profile
      personalized therapy for each child based on the molecular risk stratification of
      medulloblastoma, with a hope to improve survival outcome and reduce relapses.

PMID- 29189168
TI  - Targeting cytokines for morphine tolerance: a narrative review.
AB  - BACKGROUND: Despite its various side effects, morphine has been widely used in
      clinics for decades due to its powerful analgesic effect. Morphine tolerance is
      one of the major side effects which hinders its long-term usage for pain therapy.
      Currently, the thorough cellular and molecular mechanisms underlying morphine
      tolerance remain largely uncertain. METHODS: We searched the PubMed database with
      Medical subject headings (MeSH) including 'morphine tolerance', 'cytokines',
      'interleukin 1', 'interleukin 1 beta', 'interleukin 6', 'tumor necrosis factor
      alpha', 'interleukin 10', 'chemokines'. Manual searching was carried out by
      reviewing the reference lists of relevant studies obtained from the primary
      search. The searches covered the period from inception to November 1, 2017.
      RESULTS: The expression levels of certain chemokines and pro-inflammatory
      cytokines were significantly increased in animal models of morphine tolerance.
      Cytokines and cytokine receptor antagonist showed potent effect of alliviating
      the development of morphine tolerance. CONCLUSION: Cytokines play a fundamental
      role in the development of morphine tolerance. Therapeutics targeting cytokines
      may become alternative strategies for the management of morphine tolerance.

PMID- 29189166
TI  - Oxytocin and Eating Disorders: A Narrative Review on Emerging Findings and
      Perspectives.
AB  - BACKGROUND: The hypothalamic neuropeptide oxytocin regulates reproductive
      behavior and mother-infant interaction, and conclusive studies in humans indicate
      that oxytocin is also a potent modulator of psychosocial function. Pilot
      experiments have yielded first evidence that this neuropeptide moreover
      influences eating behavior. METHODS: We briefly summarize currently available
      studies on the involvement of the oxytocin system in the pathophysiology of
      eating disorders, as well as on the effects of oxytocin administration in
      patients with these disorders. RESULTS: Brain administration of oxytocin in
      animals with normal weight, but also with diet-induced or genetically induced
      obesity, attenuates food intake and reduces body weight. In normal-weight and
      obese individuals, acute intranasal oxytocin delivery curbs calorie intake from
      main dishes and snacks. Such effects might converge with the poignant social and
      cognitive impact of oxytocin to also improve dysfunctional eating behavior in the
      therapeutic context. This assumption has received support in first studies
      showing that oxytocin might play a role in the disease process of anorexia
      nervosa. In contrast, respective experiments in patients with bulimia nervosa and
      binge eating disorder are still scarce. CONCLUSIONS: We propose a framework of
      oxytocin's role and its therapeutic potential in eating disorders that aims at
      integrating social and metabolic aspects of its pharmacological profile, and
      ponder perspectives and limitations of oxytocin use in the clinical setting.

PMID- 29189167
TI  - 3D-QSAR and in-silico Studies of Natural Products and Related Derivatives as
      Monoamine Oxidase Inhibitors.
AB  - BACKGROUND: The computational development of human monoamine oxidase (MAO)
      inhibitors led to advancement in drug design and the treatment of many
      neurodegenerative diseases and neuropsychiatric disorders. The computational
      development of human monoamine oxidase (MAO) inhibitors led to advancement in
      drug design and the treatment of many neurodegenerative diseases and
      neuropsychiatric disorders. Different natural heterocyclic structures are
      reported to display selective MAO inhibitory activity by preclinical and in
      silico modeling. OBJECTIVE: Currently, the major interest is devoted to the study
      of natural based therapeutic agents from the different categories. Therefore, we
      presenting the review to critically discuss and outline the recent advances in
      our knowledge on the importance of natural and natural based ligand-MAO insilico
      methods for novel MAO inhibitors. DISCUSSION: Several natural and related
      synthetic heterocyclic compounds such as coumarins, beta- carboline, piperine,
      naphthoquinone, morpholine, caffeine, amphetamine moreover flavonoids, chalcones,
      xanthones, curcumin are discussed for their MAO inhibitory profile along with
      molecular docking and quantitative structure-activity relationship studies.
      CONCLUSION: It is clear that, by this computational drug design approach, more
      particular, reversible and potent compounds can be proposed as MAO inhibitors by
      exact changes on the fundamental framework.

PMID- 29189170
TI  - Paraoxonase-1: Characteristics and role in atherosclerosis and carotid artery
      disease.
AB  - Paraoxonase-1 (PON-1) is a calcium-dependent enzyme that is synthesized in the
      liver and then secreted in blood where it is bound to high density
      lipoprotein(HDL). PON-1 is a hydrolase with a wide range of substrates, including
      lipid peroxides. It is considered responsible for many of the antiatherogenic
      properties of HDL. PON-1 prevents low density lipoprotein (LDL) oxidation, a
      process that is considered to contribute to the initiation and development of
      atherosclerosis. PON-1 activity and levels areinfluenced by gene polymorphisms;
      of the 2 common variants, one is in position 192 (Q192R) and one in position 55
      (M55L). Also, many drugs affect PON-1 activity. The role of PON-1 in carotid
      atherosclerosis is inconsistent. Some studies show an association of PON-1
      polymorphisms with carotid plaque formation, whereas others do not. The aim of
      this review is to summarize the characteristics of PON-1,its interactions with
      drugs and its role in atherosclerosis and especially its relationship with
      carotid artery disease.

PMID- 29189169
TI  - Computer-aided Drug Design Applied to Parkinson Targets.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder
      characterized by debilitating motor deficits, as well as autonomic problems,
      cognitive declines, changes in affect and sleep disturbances. Although the
      scientific community has performed great efforts in the study of PD, and from the
      most diverse points of view, the disease remains incurable. The exact mechanism
      underlying its progression is unclear, but oxidative stress, mitochondrial
      dysfunction and inflammation are thought to play major roles in the etiology.
      OBJECTIVE: Current pharmacological therapies for the treatment of Parkinson's
      disease are mostly inadequate, and new therapeutic agents are much needed.
      METHODS: In this review, recent advances in computer-aided drug design for the
      rational design of new compounds against Parkinson disease; using methods such as
      Quantitative Structure-Activity Relationships (QSAR), molecular docking,
      molecular dynamics and pharmacophore modeling are discussed. RESULTS: In this
      review, four targets were selected: the enzyme monoamine oxidase, dopamine
      agonists, acetylcholine receptors, and adenosine receptors. CONCLUSION: Computer
      aided-drug design enables the creation of theoretical models that can be used in
      a large database to virtually screen for and identify novel candidate molecules.

PMID- 29189171
TI  - Challenges in Treatment of Inappropriate Sinus Tachycardia.
AB  - BACKGROUND: Inappropriate Sinus Tachycardia (IST) is a clinical syndrome
      characterized by a sinus heart rate inexplicably higher than one hundred beats
      per minute at rest that is associated with symptoms like palpitations, dyspnea or
      dizziness in the absence of primary causes of tachycardia. The diagnosis requires
      exclusion of other causes of tachycardia including medications/substances (such
      as anti-cholinergic, beta-blocker withdrawal, caffeine, and alcohol) or medical
      conditions (such as panic attacks, pulmonary embolism, fever, hyperthyroidism,
      hypovolemia, anemia, and pain). METHODS: Work up should include an EKG to
      differentiate other causes of tachycardia, 24 hour- Holter monitor if indicated,
      serum thyroid levels, hemoglobin levels and toxicology screen.
      Electrophysiological studies are not routinely recommended, but should be
      considered in certain patients in whom concurrent supraventricular tachycardia is
      suspected. CONCLUSION: The underlying pathology in IST is yet to be completely
      understood. However, it is thought that the causes of IST can be broadly
      classified into two groups; either as an intrinsic increase in sinus node
      automaticity or an extrinsic cause. Among extrinsic causes, there is evolving
      evidence that IgG anti-beta receptor antibodies are found in IST causing
      tachycardia. Managing patients with IST includes lifestyle modification, non
      pharmacological and pharmacological interventions. Ivabradine has recently
      emerged as an effective treatment of IST and was shown to be superior to beta
      blockers.

PMID- 29189174
TI  - Xanthine Oxidase Inhibitory and Molecular Docking Studies on Pyrimidones.
AB  - BACKGROUND: Xanthine oxidase is an important enzyme which catalyzes the
      production of uric acid and superoxide anion from xanthine. The over-production
      of these products leads to different disease conditions. For instance, uric acid
      is responsible for hyperuricemia, gout, and arthritis, while superoxide anion
      contributes to the oxidative stress, and related diseases. Hence XO is an
      important pharmacological target for the treatment of a range of diseases.
      METHODS: Based on the structural resemblance of pyrimidines with xanthine, a
      series of previously synthesized ethyl 6- methyl-2-oxo-1, 2, 3, 4-tetrahydro-5
      pyrimidinecarboxylate derivatives were evaluated for XO inhibitory activity.
      RESULTS: Among 25 pyrimidone derivatives, 22 were found to be good to weak
      inhibitors with IC50 values in the range of 14.4 - 418 uM. Compounds 3, 14, 15,
      18, and 21-23 were significant inhibitors, and thus analyzed for their kinetic
      parameters. Among them compounds 14, 15, 18, and 23 were competitive, 21 and 22
      showed non-competitive, while 23 was a mixed-type of inhibitor. Molecular docking
      studies highlighted the interactions of these inhibitors with critical amino
      acids of XO, such as Val1011, Phe649, Lys771, and others. Moreover, the
      cytotoxicity studies on these selected inhibitors showed all these compounds to
      be non-cytotoxic. CONCLUSION: These non-cytotoxic, significant XO inhibitors can
      thus be further investigated for the treatment of hyperuricemia, and gout.

PMID- 29189172
TI  - Cardiovascular Disease in the Setting of Human Immunodeficiency Virus Infection.
AB  - BACKGROUND: Since the introduction of Antiretroviral Therapy (ART), the life
      expectancy and health quality for patients infected with Human Immunodeficiency
      Virus (HIV) have significantly improved. Nevertheless, as a result of not only
      the deleterious effects of the virus itself and prolonged ART, but also the
      effects of aging, cardiovascular diseases have emerged as one of the most common
      causes of death among these patients. OBJECTIVE: The purpose of this review is to
      explore the new insights on the spectrum of Cardiovascular Disease (CVD) in HIV
      infection, with emphasis on the factors that contribute to the atherosclerotic
      process and its role in the development of acute coronary syndrome in the setting
      of infection. METHODS: A literature search using PubMed, ScienceDirect and Web of
      Science was performed. Articles up to Mar, 2017, were selected for inclusion. The
      search was conducted using MeSH terms, with the following key terms: [human
      immunodeficiency virus AND (cardiovascular disease OR coronary heart disease) AND
      (antiretroviral therapy AND (cardiovascular disease OR coronary heart disease))].
      RESULTS: Clinical cardiovascular disease tends to appear approximately 10 years
      before in infected individuals, when compared to the general population. The
      pathogenesis behind the cardiovascular, HIV-associated complications is complex
      and multifactorial, involving traditional CVD risk factors, as well as factors
      associated with the virus itself - immune activation and chronic inflammation -
      and the metabolic disorders related to ART regimens. CONCLUSION: Determining the
      cardiovascular risk among HIV-infected patients, as well as targeting and
      treating conditions that predispose to CVD, are now emerging concerns among
      physicians.

PMID- 29189173
TI  - Prodrugs for Nitroreductase Based Cancer Therapy- 1: Metabolite Profile, Cell
      Cytotoxicity and Molecular Modeling Interactions of Nitro Benzamides with Ssap
      NtrB.
AB  - BACKGROUND: Directed Enzyme Prodrugs Therapy (DEPT) as an alternative method
      against conventional cancer treatments, in which the non-toxic prodrugs is
      converted to highly cytotoxic derivative, has attracted an ample attention in
      recent years for cancer therapy studies. OBJECTIVE: The metabolite profile, cell
      cytotoxicity and molecular modeling interactions of a series of nitro benzamides
      with Ssap-NtrB were investigated in this study. METHOD: A series of nitro
      substituted benzamide prodrugs (1-4) were synthesized and firstly investigated
      their enzymatic reduction by Ssap-NtrB (S. saprophyticus Nitroreductase B) using
      HPLC analysis. Resulting metabolites were analyzed by LC-MS/MS. Molecular docking
      studies were performed with the aim of investigating the relationship between
      nitro benzamide structures (prodrugs 1-4) and Ssap-NtrB at the molecular level.
      Cell viability assay was conducted on two cancer cell lines, hepatoma (Hep3B) and
      colon (HT-29) cancer models and healthy cell model HUVEC. Upon reduction of
      benzamide prodrugs by Ssap-NtrB, the corresponding amine effectors were tested in
      a cell line panel comprising PC-3, Hep3B and HUVEC cells and were compared with
      the established NTR substrates, CB1954 (an aziridinyl dinitrobenzamide). RESULTS:
      Cell viability assay resulted in while prodrugs 1, 2 and 3 had no remarkable
      cytotoxic effects, prodrug 4 showed the differential effect, showing moderate
      cytotoxicity with Hep3B and HUVEC. The metabolites that obtained from the
      reduction of nitro benzamide prodrugs (1-4) by Ssap-NtrB, showed differential
      cytotoxic effects, with none toxic for HUVEC cells, moderate toxic for Hep3B
      cells, but highly toxic for PC3 cells. CONCLUSION: Amongst all metabolites of
      prodrugs after Ssap-NtrB reduction, N-(2,4- dinitrophenyl)-4-nitrobenzamide (3)
      was efficient and toxic in PC3 cells as comparable as CB1954. Kinetic parameters,
      molecular docking and HPLC results also confirm that prodrug 3 is better for Ssap
      NtrB than 1, 2 and 4 or known cancer prodrugs of CB1954 and SN23862,
      demonstrating that prodrug 3 is an efficient candidate for NTR based cancer
      therapy.

PMID- 29189175
TI  - Fracture Risk Associated with Use of Antibiotics.
AB  - BACKGROUND: Data have pointed at an impaired fracture healing with
      fluoroquinolones and thus potentially a decreased bone biomechanical competence.
      OBJECTIVES: To study fracture risk associated with antibiotics. METHODS: It is a
      case control study. There were 124,655 fracture cases and 373,962 age and gender
      matched controls. The main exposure was use of various groups of antibiotics.
      Confounder control was performed for social variables, contacts to hospitals and
      general practitioners, alcoholism and a number of other variables. RESULTS: An
      increased risk of any fracture (OR =1.45, 95% CI: 1.42 -1.49), hip (1.46, 95% CI:
      1.35- 1.58), forearm (1.67, 95% CI: 1.55 -1.80), and spine fractures (1.38, 95%
      CI: 1.18-1.60) was seen with the use of dicloxacillin and flucloxacillin. There
      was a dose response relationship for overall risk of fractures, hip, and forearm
      fractures but not for spine fractures with dicloxacillin and flucloxacillin. None
      of the other groups of antibiotics against bacteria, tuberculosis, virus, and
      fungi were systematically associated with any major change in the risk of
      fractures. CONCLUSION: Dicloxacillin and flucloxacillin seem associated with an
      increased risk of fractures. The cause for this increase has to be determined but
      may be related to their use against infections of the bone, the increase thus
      rather being due to the underlying disease than the drug. Other types of
      antibiotics especially the fluoroquinolones were not systematically associated
      with an increased risk of fractures.

PMID- 29189176
TI  - The Emerging Role of Complement C3 as A Biomarker of Insulin Resistance and
      Cardiometabolic Diseases: Preclinical and Clinical Evidence.
AB  - BACKGROUND: An intricate network of reciprocal interactions between adipose
      tissue and immune system have been largely demonstrated, leading to the well
      accepted concept of insulin resistance as a low grade inflammatory state and,
      conversely, chronic high-grade inflammation as a dysmetabolic condition. Immune
      homeostasis is regulated by several players including the complement system, a
      complex protein network at the crossroad between the innate and adaptive arms of
      the human defences against pathogens. OBJECTIVE: Complement C3 represents the
      nodal point of the complement cascade independently of the pathway recruited. Aim
      of this review is to collect the evidence supporting the role of complement C3 as
      a candidate biomarker of insulin resistance and other metabolic disorders.
      METHODS: We reviewed the available evidence pointing to a role of complement
      system, and in particular complement C3, in insulin resistance and other
      cardiometabolic diseases including diabetes (T2D), hypertension, non-alcoholic
      fatty liver disease (NAFLD) and atherosclerosis. RESULTS: Compelling preclinical
      evidence demonstrated a role of adipose-tissue C3 and its cleavage products C3a
      and acylation stimulating protein (ASP) in adipose tissue inflammation and
      insulin resistance. To further support this hypothesis, several clinical studies,
      both cross-sectional and longitudinal, confirmed this association in independent
      cohorts. Moreover, preliminary evidence support a role of complement C3 in other
      cardiometabolic diseases such as hypertension, NAFLD and atherosclerosis.
      CONCLUSION: Future studies are needed to fully confirm the usefulness of C3 as a
      clinical biomarker and to establish accurate cut-off values. Moreover, the
      therapeutic potential of C3 modulation in either cardiometabolic and inflammatory
      diseases need to be investigated.

PMID- 29189177
TI  - Brain Cancer: Implication to Disease, Therapeutic Strategies and Tumor Targeted
      Drug Delivery Approaches.
AB  - BACKGROUND: Cancer is one of the leading causes of morbidity and mortality
      worldwide. Brain cancer is identified as one of the most formidable forms of
      cancer due to several hurdles posed by the anatomy and physiology of the brain on
      the therapeutic strategies employed for treating brain cancer. Poor prognosis and
      high relapse rate further aggravate the situation leading to the high mortality
      rate in brain cancer. OBJECTIVE: The present review gives a brief insight on
      different aspects of brain cancer by elucidating its types, causative factors,
      associated symptoms, diagnostic techniques, treatment strategies and limitations
      of current treatment strategies. The review summarizes novel drug delivery based
      treatment strategies for tumor targeting. METHODS: Conventional surgical or
      chemotherapy based strategies are less efficient for treating brain cancer.
      Surgery is risky because extracting the tumors can permanently damage the brain
      and alter the patient's ability to function. Sometimes, surgery cannot be
      performed because of the anatomical location of the tumor which is beyond the
      reach or near to any vital region. Drug based therapy requires heavy doses to
      cross the blood brain barrier leading to systemic toxicity. The review summarizes
      fifteen different patented technologies for targeting the drug substance
      specifically to the tumor site in the brain. RESULT: Targeted drug delivery
      strategies serve as an efficient tool for treating brain cancer. CONCLUSION:
      Novel strategies focused towards targeting drug substances specifically to brain
      tumor site would increase the therapeutic efficiency and reduce the toxicity of
      chemotherapeutics.

PMID- 29189178
TI  - Targeting Mevalonate Pathway in Cancer Treatment: Repurposing of Statins.
AB  - BACKGROUND: Modifications of lipid metabolism have been progressively accepted as
      a hallmark of tumor cells and in particular, an elevated lipogenesis has been
      described in various types of cancers. OBJECTIVE: Important or deregulated
      activity of the mevalonate pathway has been demonstrated in different tumors and
      a wide range of studies have suggested that tumor cells are more dependent on the
      unceasing availability of mevalonate pathway metabolites than their non-malignant
      complements. METHODS: This study provides an overview of the state of the art of
      statins treatment on human cancer. RESULTS: In recent times, various actions have
      been proposed for statins in different physiological and pathological conditions
      beyond anti-inflammation and neuroprotection activity. Statins have been shown to
      act through mevalonate-dependent and -independent mechanisms able to affect
      several tissue functions and modulating specific signal transduction pathways
      that could account for statin pleiotropic effect. Based on their characteristics,
      statins represent ideal candidates for repositioning in cancer therapy.
      CONCLUSION: In this review article, we provide an overview of the current
      preclinical and clinical status of statins as antitumor agents. In addition, we
      evaluated various patents that describe the role of mevalonate pathway inhibitors
      and methods to determine if cancer cells are sensitive to statins treatment.

PMID- 29189179
TI  - Computational study of the binding modes of diverse DPN analogues on estrogen
      receptors (ER) and the biological evaluation of a new potential antiestrogenic
      ligand.
AB  - Estrogen (17beta-estradiol) is essential for normal growth and differentiation in
      the mammary gland. In the last three decades previous investigations have
      revealed that estrogen receptor alpha (ERalpha) plays a critical role in breast
      cancer. More recently, observations regarding the widespread expression of ERbeta
      like proteins in normal and neoplastic mammary tissues have suggested that ERbeta
      is also involved in the mentioned pathology. Design of new drugs both steroidal
      and nonsteroidal that target any of these receptors  represents a  promise to
      treat breast cancer, although it remains a challenge due to the sequence
      similarity between their catalytic domains. In this work we propose a  new set of
      compounds that could effectively target the estrogen receptors ERalpha and
      ERbeta. These ligands were designed based on the chemical structure of the ERbeta
      selective agonist diarylpropionitrile (DPN). The designed ligands were  submitted
      to in silico ADMET studies, yielding in a filtered list of ligands that showed
      better drug-like properties. Molecular dynamics simulations and docking analysis
      were carried-out employing these compounds  from which two of them were chosen 
      considering their promising characteristics obtained from theoretical results.
      They were chemically synthetized and during the process, two precursor ligands
      were also  obtained. These four ligands were subjected to biological studies,
      where it could be detected that ligand  mol60b showed inhibitory activity and its
      ability to activate the transcription via an estrogenic mechanism of action was
      also determined. Interestingly, this result coincides well to the  fact that the
      complex of ERbeta-mol60b showed the highest DeltaGbind value from the binding
      free energy calculations.

PMID- 29189180
TI  - Design, Synthesis and Anti-breast Cancer activity of Some Novel substituted
      Isoxazoles as Anti-breast Cancer Agent.
AB  - A novel series of isoxazole (S21-S30) derivatives were designed, synthesized and
      screened for their anticancer activity against estrogen receptor-positive MCF-7
      and negative MDA-MB-435 breast cancer cell lines. The synthesized derivative has
      ability to inhibit the growth of the human breast cancer cell line at low
      concentrations. In-vivo anticancer activity was performed on virgin female
      sprague dawley rats. The result shows that the compound S23 has more selectivity
      and marked estrogen modulator activity than the standard tamoxifen.

PMID- 29189181
TI  - "Good Fashion is Evolution, Not Revolution" - Methods to Enhance Existing
      Anticancer Medicines, Primarily with the Use of Transition Metal.
AB  - The constant search for successful cancer therapies lasts for decades. Apart from
      the huge scientific effort and enormous sum of spent money, only a small amount
      of newly developed medicines move into clinical use (only 94 registered
      anticancer drugs in the last 12 years). Anticancer regimes are still overcome by
      drugs invented over 50 years ago such as cisplatin and doxorubicin. Significant
      progress in the development of improved anticancer drugs was made due to multiple
      studies on the relationship between the molecular structure of chemical compounds
      and their cytostatic activity. A number of ligands (mainly organic) with quite
      effective anticancer properties are known, but they show insufficient activity,
      selectivity and multidrug resistance. Formation of transition metal - ligand
      complexes (with proven anticancer effect) changes the properties of the latter.
      The factors that affect the cytotoxic properties of metal complexes are: the type
      of ligand and metal, the nature of the connection between metal and ligand, and
      the distribution of electronic charge density in the formed complexes. Here, we
      report the recent efforts to improve existing compounds with confirmed anticancer
      activity. They seem to be unappreciated as their effects appear to be less
      spectacular than that of targeted anticancer drugs (i.e. based on antibodies or
      small RNAs).

PMID- 29189182
TI  - Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2
      Thioxoimidazolidinones.
AB  - BACKGROUND: Some 2-thioxoimidazolidinones have been reported as anti-prostate and
      anti-breast cancer agents through their inhibitory activity on topoisomerase I
      that is considered as a potential chemotherapeutic target. OBJECTIVE: A new
      series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S
      methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity
      against human prostate cancer cell line (PC-3), human breast cancer cell line
      (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). Results and
      Method: While compounds 10a-f showed a broad range of activities against PC-3 and
      MCF-7 cell lines (IC50 = 34.0 - 186.9 and 24.6 - 147.5 uM respectively), the S
      methyl analogs 11a-f showed (IC50 = 22.7 - 198.5 and 16.9 - 188.2 uM
      respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 uM
      respectively). 11c (IC50 = 22.7 and 29.2 uM) and 11f (IC50 = 28.7 and 16.9 uM)
      were the most potent among all compounds against both PC-3 and MCF-7 respectively
      with no cytotoxicity against WI-38. CONCLUSION: The newly synthesized compounds
      showed good activity against PC-3 and MCF-7 cell lines in comparison with 5
      fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to
      its known inhibitors and significantly inhibited its DNA relaxation activity in a
      dose dependent manner which may rationalize their molecular mechanism as
      cytotoxic agents.

PMID- 29189183
TI  - A Multicenter Study of IgE Sensitization to Anisakis simplex and Diet
      Recommendations.
AB  - BACKGROUND: Allergy to Anisakis simplex (s.) is spreading due to the increased
      consumption of raw, smoked or marinated fish. In man, Anisakis s. can directly
      attack the gastrointestinal mucosa, provoking a parasitosis known as anisakiasis,
      or giving rise to the formation of IgE and, finally, inducing IgE-mediated
      reactions like urticaria, angioedema and anaphylactic shock. During recent years,
      a dietary approach to Anisakis s. infestation has also been addressed. METHODS: A
      total of 620 patients with urticaria, angioedema, or both and a history of
      anaphylaxis following consumption of raw, smoked or marinated fish were
      recruited, evaluated for specific IgE levels to Anisakis s. and subjected to Skin
      Prick test. Following 18 month fish-free diet, patients were reevaluated at 6, 12
      and 18 months, respectively. Patients undergoing diet were selected among those
      who had a clinical history with multiple accesses to first aid. RESULTS: After 6
      month fish-free diet, we recorded an improvement of symptoms and a remarkable
      reduction of specific IgE levels. The extension of the diet over 6 months in some
      cases resulted in a further reduction of specific IgE levels. CONCLUSION: Data
      obtained confirm the importance of a fish-free diet in patients with severe
      symptoms since a new antigenic exposure coincides with a relapse of symptoms and
      increased IgE levels. This last point should be kept in mind and carefully
      evaluated in patients at risk for anaphylaxis or angioedema.

PMID- 29189184
TI  - Impact of Electron-Beam Irradiation on Functional Attributes of Seeds of Two
      Coastal Wild Legume Landraces of Canavalia.
AB  - BACKGROUND: Vegetable proteins have widespread application in the food industry
      as functional ingredients in food formulations according to the recent patents.
      Requirement to develop less expensive protein-rich supplementary foods has
      resulted in shift of emphasis towards lesser known wild than popular legumes.
      OBJECTIVE: The aim of this study is to expose seeds of two coastal sand dune wild
      legumes of the Southwest India (Canavalia cathartica and C. maritima) to
      different doses of electron-beam (EB) irradiation to assess changes in functional
      attributes. METHOD: Intact dried seeds were exposed to EB irradiation (2.5, 5,
      10, 15 kGy). Protein solubility, gelation concentration, water-absorption
      capacity, oil-absorption capacity, emulsion properties and foam properties of
      control and irradiated seeds were assessed by standard methods. RESULTS: Protein
      solubility of both seed flours attained the highest at 2.5 kGy, followed by
      gradual dosedependent decrease. The gelation concentration increased in C.
      cathartica only at 5 kGy, while it decreased in C. maritima at 2.5 kGy without
      further change at higher doses. The water-absorption capacity of C. maritima was
      significantly higher than C. cathartica in control sample, while at 15 kGy C.
      cathartica showed significantly higher absorption capacity than C. maritima. The
      oil-absorption capacity was significantly higher in C. maritima than C.
      cathartica in control as well as all doses of irradiation. Emulsion activity of
      C. maritima was slightly higher than C. cathartica in control and irradiated
      samples, while both seeds showed similar emulsion stability in control with
      significant increase in C. cathartica at 10 kGy and 15 kGy. The foam capacity in
      both seeds was similar up to 2.5 kGy followed by significant increase in C.
      maritima at 5 kGy and 10 kGy. The foam stability was significantly higher C.
      cathartica than C. maritima in control as well as in irradiated samples. The foam
      capacity was higher in C. maritima than C. cathartica in control and irradiated
      samples, which showed gradual time-dependent decrease in stability with higher
      stability at 8 hr in C. cathartica than C. maritima. CONCLUSION: Improved
      functional properties (protein solubility, emulsion stability and foam capacity)
      and decreased gelation concentration in seeds of C. maritima irradiated at 5 kGy
      is advantageous in the production of functional foods. Even though both species
      of Canavalia grew on the coastal sand dunes and their seeds were exposed to same
      doses of radiation, they differed in functional attributes confirm that it is
      species-specific. Canavalia seeds being rich in proteins, carbohydrates,
      essential amino acids, essential fatty acids and bioactive components, further
      studies on the impact of EB irradiation helps in optimization of nutraceutical
      potential as well as functional attributes for future applications.

PMID- 29189185
TI  - Enhanced Both in vitro and in vivo Kinetics by SLNs Induced Transdermal System of
      Furosemide: A Novel Approach.
AB  - BACKGROUND: Furosemide is a potent diuretic agent used to treat pulmonary
      arterial hypertension. Variable dosage regimen and poor pharmacokinetic
      parameters have led to the development of transdermal drug delivery system.
      OBJECTIVE: Patent on suitability of multi-lamellar structures for excellent
      transdermal delivery (US0367475A1) has encouraged us to formulate the solid lipid
      nanoparticles (SLNs) induced transdermal systems of furosemide to enhance the
      kinetic properties without incorporating any penetration enhancer and rate
      limiting polymers. METHODS: SLNs were prepared by hot homogenization and ultra
      sonication method; optimization was done based on entrapment efficiency and
      particle size. Optimized SLNs were incorporated in to transdermal patches by
      solvent casting method. In vitro and in vivo studies were carried out for
      characterization of transdermal patches. RESULTS: SLNs of F9 (GMS: Span 60:
      Pluronic F 68 in 6:2.5:0.2) were optimized for incorporating in to transdermal
      system (entrapment efficiency 96.5+/-0.045%, particle size 69.6+/-1.48nm and in
      vitro release 94.38+/-1.02%). Transdermal patches were formulated using
      combinations of hydrophilic and hydrophobic polymers to study the diffusion
      kinetics. Formulation FS1 (HPMC 4 parts) was optimized for further studies (in
      vitro release 98.11+/-1.21% with flux of 58.726+/-0.023ug/cm2/h) and no
      significant difference from ex vivo permeation studies was observed. Drug release
      followed mixed order diffusion kinetics and super case -II transport mechanism.
      In vivo pharmacokinetic data of SLNs induced transdermal system suggested a 3.6
      times increase in AUC and 5.4 times increase in MRT when compared with oral
      route. CONCLUSION: The SLNs induced transdermal patch was found to beneficial in
      enhancing kinetic properties both in vitro and in vivo.

PMID- 29189186
TI  - Furosemide - Soluplus(r) Solid Dispersion: Development and Characterization.
AB  - BACKGROUND: Recent patents reveal that Soluplus(r) has proved to be a promising
      excipient that modulates dissolution characteristics of many active
      pharmaceutical ingredients (WO2016161995A1, WO2016169534A1 and WO2016165676A1).
      OBJECTIVE: Current article investigates stable solid solution of furosemide with
      Soluplus(r) to enhance the dissolution properties of the drug. METHOD: Drug to
      carrier ratios to prepare solid dispersion were selected based on the phase
      solubility study. Solid dispersions of furosemide with Soluplus(r) were prepared
      by solvent evaporation and fusion methods. Physicochemical parameters were
      characterized using Fourier transform infra-red spectrophotometer, thermo-
      gravimetric analyzer, differential thermal analyzer, and scanning electron
      microscopy. Drug release from the formulations was compared using USP type II
      (paddle type) dissolution apparatus containing 900 mL of phosphate buffer (pH -
      6.8) maintained at 37+/-0.5 degrees C at a paddle rotation speed of 50rpm.
      RESULTS: Fourier transform infra-red spectroscopy confirmed absence of any
      chemical interaction while thermo-gravimetry and differential thermal analysis
      showed evidences of formation of a solid solution of furosemide. No furosemide
      crystals were observed under scanning electron microscope in case of solid
      dispersion. Dissolution data indicated that furosemide dissolution was enhanced
      to a great extent and drug to carrier ratio of 1:10 was found to be most
      suitable. CONCLUSION: Solid dispersions prepared by fusion method exhibited
      faster drug release compared to those prepared by solvent evaporation.

PMID- 29189187
TI  - Thymoquinone a Potential Therapeutic Molecule from the Plant Nigella sativa: Role
      of Colloidal Carriers in its Effective Delivery.
AB  - BACKGROUND: From the past few decades, remarkable awareness has laid on the use
      of herbal medicines in pharmaceutical research. Thymoquinone (TQ), the main
      chemical constituent of Nigella Sativa (NS) plant, has been extensively explored,
      and revealed an array of therapeutic benefits, in different in vitro, and in vivo
      conditions. This review provides brief outline of the diverse therapeutics
      actions of TQ, and NS, viz. anti-oxidant, anti-inflammatory, anti-cancer, anti
      diabetic, gastroprotective, hepato-protective, anti-microbial and anti
      histaminic. Besides, a special emphasis has given on the use of colloidal drug
      delivery systems exploited hitherto, for the effective delivery of TQ and NS.
      OBJECTIVE: The main objective of the review was to include an intensive patent
      literature, available on TQ and NS, for its usefulness in different therapeutic
      conditions. METHODS: We embarked an organized search of bibliographic databases
      for peer-reviewed research literature and patent databases. The characteristics
      of screened papers were described, and a rational qualitative content analysis
      approach was applied to analyze the interventions and findings of included
      studies using a theoretical framework. RESULTS: In the past, various studies have
      carried out which undoubtedly vouch for the multifarious therapeutic roles of TQ
      in an array of different diseases. More than 670 research papers and around 50
      review articles are available on TQ and NS in PubMed database until now,
      suggesting its high significance. Around 12 review articles published only on the
      anticancer potential, while the others on its anti- inflammatory and anti-oxidant
      potential. Around 120 papers included in the review revealed the therapeutic
      benefits of TQ. In addition to this, an intensive patent literature is also
      available on TQ and NS, for its usefulness in different therapeutic conditions.
      CONCLUSION: The findings of this review confirm the effectiveness of TQ in
      various pathologies viz. inflammation, cancer, diabetes, gastric, hepatic,
      microbial and allergies. However, the complete clinical benefit of TQ has not yet
      been realized, owing to its poor biopharmaceutical properties. Nevertheless,
      colloidal drug delivery carrier systems, could be impending in bringing forth
      this potential molecule to reality.

PMID- 29189188
TI  - Complementary, Alternative and Integrative Medicine for Childhood Atopic
      Dermatitis.
AB  - BACKGROUND: Atopic Dermatitis (AD) is a chronic relapsing dermatosis associated
      with itch, sleep disturbance and poor quality of life. Treatment of AD includes
      the use of emollients, and topical and systemic immunomodulating agents. Many
      patients also use complementary and alternative medicine (CAM). OBJECTIVE: This
      article reviews the pathophysiology of AD, clinical trials and recent patents
      involving various modalities of CAM in the treatment of AD. METHODS: A
      Medline/Pubmed search was conducted using Clinical Queries with the key terms
      "Chinese Medicine OR Complementary and Alternative medicine" AND "Eczema OR
      Atopic dermatitis". The search strategy included meta-analyses, Randomized
      Controlled Trials (RCTs), clinical trials, reviews and pertinent references.
      Patents were searched using the key term "atopic dermatitis" from
      www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com. RESULTS:
      Only a few RCTs evaluated the efficacy of Chinese medicinal herbs in treating AD.
      There was some evidence for other modalities of CAM. Integrative Medicine (IM)
      usually refers to the various forms of CAM that combine conventional western
      medicine and Chinese medicine. Supporting evidence for the efficacy of IM in the
      treatment of AD is presently lacking. Integration is difficult. Western medicine
      practitioners are often ignorant about CAM and IM. Parents are concerned about
      the potential side effects of Western medicine and will tend to be non-compliant
      with the conventional Western component of IM. Recent patents on CAM and IM are
      reviewed. Most CAM patents are herbal compositions, evidence on their efficacy is
      generally lacking. CONCLUSION: AD is a complex disease. The psychodynamics of the
      child and his/her family is the reason for the often suboptimal outcomes. Both
      Western and CAM practitioners should collaborate to create a mutually encouraging
      environment for the advances of IM. CAM and IM publications and patents are
      reviewed. Evidence of their efficacy is generally lacking. Further research is
      needed.

PMID- 29189189
TI  - Selective Suppression of CYP3A4 mRNA and Enzyme Activity by Epidermal Growth
      Factor in Plated Human Hepatocytes.
AB  - BACKGROUND: Epidermal Growth Factor (EGF) is a well-known mitogen that has
      importance in cell proliferation and differentiation. This property has led to
      the common use of EGF as an additive to some cell culture media. EGF has been
      previously shown to modulate constitutive Cytochrome P450 (CYP) expression in
      vitro. OBJECTIVES: To assess the influence of EGF on the basal and induced
      expression of CYP3A4, CYP1A2 and CYP2B6 in plated human hepatocytes. METHODS:
      Human hepatocytes were treated with EGF with and without in the presence of
      positive control inducers. After treatment, CYP isoform mRNA expression and
      enzyme activity were measured. RESULTS: EGF at concentrations ranging from 0.001
      500 ng/mL resulted in a concentration-dependent decrease in basal CYP3A4
      catalytic activity by up to 92%. In contrast, rifampicin (RIF)-induced activity
      was decreased only slightly (up to 23%). CYP3A4 mRNA also decreased in an EGF
      concentrationdependent manner. In contrast to CYP3A4, CYP1A2 and CYP2B6 activity
      and mRNA were either not suppressed or suppressed to a lower extent. The
      preferential effect with CYP3A4 was confirmed in 4 additional donors using a
      single concentration of EGF (10 ng/mL) and time-dependence experiments revealed
      that suppression appeared after only 24h of treatment. CONCLUSION: Because of the
      larger effect on the basal CYP3A4 compared to the induced response, EGF as a
      media additive enables a higher dynamic range in a CYP3A4 induction assay,
      potentially expanding the range of donor hepatocytes suitable for use in
      induction studies. These findings also suggest that EGF may be an important
      regulator of CYP3A4 expression in vivo.

PMID- 29189190
TI  - Role of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treatment of
      Addiction and Related Disorders: A Systematic Review.
AB  - BACKGROUND: Addiction and related disorders are devastating with their tremendous
      social, psychological, and physical consequences for which development of
      optimally effective treatments is long overdue. Repetitive Transcranial Magnetic
      Stimulation (rTMS) is relatively safe and is becoming an emerging therapeutic
      tool for these conditions. METHODS: This systematic review was conducted using
      PubMed, PsycINFO, PsychiatryOnline and Cochrane Library ranging from year 2001 to
      2017. RESULTS: Our search selected 70 related articles of which, based on the
      Strength of Recommendation Taxonomy (SORT) guidelines, 11 indicated Level-1 study
      quality and class-B strength of recommendation for rTMS in nicotine addiction
      (effective in 218/289 subjects who received rTMS as found in 11 studies). Level
      2/Class-B evidence was found for alcohol and cocaine addictions (Alcohol:
      effective in 126/193 subjects who received rTMS as found in 8 studies; Cocaine:
      effective in 86/128 subjects, as found in 5 studies). For food cravings, Level
      3/Class-B evidence was noted (effective in 134/169, found in 7 studies). However,
      the evidence was limited to Level-3/Class-C for heroin (10/20 subjects received
      active rTMS, effective in 1 study), methamphetamine (33/48 subjects received
      active rTMS, effective in 2 studies), cannabis (18/18 subjects received active
      rTMS, effective in 1 study), and pathological gambling (31/31 subjects received
      active rTMS, effective in 2 studies). CONCLUSION: rTMS may serve as an emerging
      therapeutic option for addiction and related disorders. The major lacunae include
      important methodological limitations and dearth of knowledge about precise
      mechanism of action that need to be addressed in the future studies.

PMID- 29189191
TI  - Edible Mushrooms from Niger Delta, Nigeria with Heavy Metal Levels of Public
      Health Concern: A Human Health Risk Assessment.
AB  - BACKGROUND: Mushrooms (US6759049B2, CA2372185A1, DE60108325D1) can be
      contaminated by heavy metals as described in various patents. OBJECTIVE: This
      study has determined the potential human health risk associated with the
      consumption of mushroom in Niger Delta, Nigeria. Concentrations of Pb, Cd, Sn,
      Cu, Ni, Al and Zn in both wild/cultivated mushroom and background soil/substrate
      were determined using Atomic Absorption Spectrometer (AAS). METHODS: Heavy metal
      pollution was calculated using Bio-Concentration Factor (BCF) and Pollution Load
      Index (PLI) while human health risk assessment employed Estimated Daily Intake
      (EDI), Target Hazard Quotient (THQ), Hazard Index (HI), Carcinogenic Risk (CR)
      and Total Cancer Risk (TCR). The mean concentration of metals in mushroom and
      soil/substrate ranged from 0.021 mg/kg - 29.16 mg/kg and 0.01 mg/kg - 56.11
      mg/kg. When compared with standards by WHO, EU, SON, DPR, USEPA and NAFDAC, 100%
      violation was observed in Ni, Cu, Cd, Zn and partial violation by Pb in the
      mushroom sample although soil heavy metal concentrations were within safe limits.
      RESULTS: There was bioconcentration and heavy metal enrichment as PLI ranged from
      3.39 - 23.58. Estimated daily intakes were (0.00 - 0.47, 0.00 - 0.51 and 0.00 -
      1.17) mg/kg/day and THQ were (0.01 - 0.46, 0.01 - 0.31 and 0.03 - 1.51) for
      adults, adolescents and children respectively. There was a violation of
      Permissible Tolerable Daily Intakes (PTDI) set by JECFA. Hazard indices were all
      >1, another indication of health concern. CONCLUSION: Nickel showed the highest
      carcinogenic risk with values of 4.83E-04 - 1.43E-01, 5.31E-04 - 1.00E-01 and
      1.20E-03 - 2.29E-01 for adults, adolescents and children respectively. About 80%
      of TCR ranged from x10-1 - x10-3. Consumption of mushroom in Niger delta-Nigeria
      may pose significant health risk.

PMID- 29189192
TI  - Intake of dietary fat and fat subtypes and risk of premenstrual syndrome in the
      Nurses' Health Study II.
AB  - Approximately 8-20 % of reproductive-aged women experience premenstrual syndrome
      (PMS), substantially impacting quality of life. Women with PMS are encouraged to
      reduce fat intake to alleviate symptoms; however, its role in PMS development is
      unclear. We evaluated the association between dietary fat intake and PMS
      development among a subset of the prospective Nurses' Health Study II cohort. We
      compared 1257 women reporting clinician-diagnosed PMS, confirmed by premenstrual
      symptom questionnaire and 2463 matched controls with no or minimal premenstrual
      symptoms. Intakes of total fat, subtypes and fatty acids were assessed via FFQ.
      After adjustment for age, BMI, smoking, Ca and other factors, intakes of total
      fat, MUFA, PUFA and trans-fat measured 2-4 years before were not associated with
      PMS. High SFA intake was associated with lower PMS risk (relative risk (RR)
      quintile 5 (median=28.1 g/d) v. quintile 1 (median=15.1 g/d)=0.75; 95 % CI 0.58,
      0.98; P trend=0.07). This association was largely attributable to stearic acid
      intake, with women in the highest quintile (median=7.4 g/d) having a RR of 0.75
      v. those with the lowest intake (median=3.7 g/d) (95 % CI 0.57, 0.97; P
      trend=0.03). Individual PUFA and MUFA, including n-3 fatty acids, were not
      associated with risk. Overall, fat intake was not associated with higher PMS
      risk. High intake of stearic acid may be associated with a lower risk of
      developing PMS. Additional prospective research is needed to confirm this
      finding.

PMID- 29189193
TI  - A comparison of heart rate variability, n-3 PUFA status and lipid mediator
      profile in age- and BMI-matched middle-aged vegans and omnivores - CORRIGENDUM.

PMID- 29189195
TI  - Correcting nutritional biomarkers for the influence of inflammation.

PMID- 29189194
TI  - The dietary diversity and stunting prevalence in minority children under 3 years
      old: a cross-sectional study in forty-two counties of Western China.
AB  - As a key indicator of childhood malnutrition, few studies have focused on
      stunting in relation to various socio-economic factors in which disadvantaged
      groups face in China. We conducted a community-based cross-sectional study
      incorporating forty-two rural counties in seven western provinces of China in
      2011. In total, 5196 children aged 6-23 months were included. We used Poisson
      regression to examine risk factors for inadequate minimum dietary diversity (MDD)
      and stunting status, respectively. Overall, the proportion of children not
      meeting MDD was 44.5 %. Children aged 6-11 months (adjusted risk ratio
      (ARR)=1.39; 95 % CI 1.31, 1.49), with two siblings (ARR=1.09; 95 % CI 1.02,
      1.17), delivered at home (ARR=1.30; 95 % CI 1.20, 1.41), within Yi (ARR=1.15; 95
      % CI 1.04, 1.28) or Uighur groups (ARR=1.52; 95 % CI 1.36, 1.71), with an
      illiterate caregiver (ARR=2.12; 95 % CI 1.52, 2.96), receiving lowest income
      (ARR=1.32; 95 % CI 1.17, 1.50), and with breast-feeding in the last day
      (ARR=1.55; 95 % CI 1.44, 1.66) were more likely to have inadequate MDD. Moreover,
      inadequate MDD was positively associated with stunting (ARR=1.15; 95 % CI 1.01,
      1.31). Other determinants for stunting were age, sex, place of delivery, minority
      group and income. The stunting prevalence and proportion of inadequate MDD
      remained high in Western China; to reduce stunting rates of ethnic minorities,
      further efforts addressing appropriate dietary feeding practices are needed,
      especially within these groups.

PMID- 29189197
TI  - HR-pQCT detects alterations in bone microstructure in men with CKD stages 3 and
      4, which are influenced by hormonal changes and body composition?.
AB  - INTRODUCTION: Factors associated with osteodystrophy in predialysis patients are
      poorly understood. In the present study, we attempted to evaluate the impact of
      body composition and hormonal regulatory factors on the bone microstructure in a
      group of men with chronic kidney disease (CKD) stages 3 and 4. MATERIALS AND
      METHODS: 46 men, aged 50 - 75 years, with previously unrecognized CKD were
      evaluated by high-resolution peripheral quantitative computed tomography (HR
      pQCT), and dual-energy X-ray absorptiometry (DXA). HR-pQCT parameters were
      correlated with estimated glomerular filtration rate (eGFR), age, body mass index
      (BMI), muscle mass index (MMI), and biochemistry. RESULTS: As compared to
      patients in stage 3 CKD, those with stage 4 CKD showed lower serum 25
      hydroxyvitamin D (25(OH)D) and bicarbonate levels, and higher serum fibroblast
      growth factor 23 (FGF-23) and parathyroid hormone (PTH) levels. They also
      exhibited lower total, trabecular, and cortical volumetric bone mineral density,
      lower trabecular bone volume/tissue volume, trabecular number, trabecular and
      cortical thickness, and increased heterogeneity of the trabecular network. In the
      whole cohort, cortical bone density and thickness were negatively associated with
      age, PTH, and FGF-23, and positively with BMI. Trabecular bone parameters were
      positively associated with MMI and 25(OH)D. After simultaneously adjusting for
      age and eGFR, BMI, and MMI remained significantly associated with bone
      microstructural variables. CONCLUSION: HR-pQCT showed significant differences in
      bone microstructure in stage 4 vs. stage 3 CKD patients. Increased BMI, probably
      due to increased muscle mass, may favorably affect bone architecture in
      predialysis CKD patients.?.

PMID- 29189196
TI  - Iron, zinc, vitamin A and selenium status in a cohort of Indonesian infants after
      adjusting for inflammation using several different approaches.
AB  - Inflammation confounds the interpretation of several micronutrient biomarkers
      resulting in estimates that may not reflect the true burden of deficiency. We
      aimed to assess and compare the micronutrient status of a cohort of Indonesian
      infants (n 230) at aged 6, 9 and 12 months by ignoring inflammation (unadjusted)
      and adjusting four micronutrient biomarkers for inflammation with C-reactive
      protein (CRP) and alpha-1-glycoprotein (AGP) using the following methods: (1)
      arithmetic correction factors with the use of a four-stage inflammation model;
      and (2) regression modelling. Prevalence of infants with any inflammation (CRP>5
      mg/l and/or AGP>1 g/l) was about 25% at each age. Compared with unadjusted
      values, regression adjustment at 6, 9 and 12 months generated the lowest (P50 %
      across all ages. In conclusion, without inflammation adjustment, Fe deficiency
      was grossly under-estimated and vitamin A and Zn deficiency over-estimated,
      highlighting the importance of correcting for the influence of such, before
      implementing programmes to alleviate micronutrient malnutrition. However, further
      work is needed to validate the proposed approaches with a particular focus on
      assessing the influence of varying degrees of inflammation (i.e. recurrent acute
      infections and low-grade chronic inflammation) on each affected nutrient
      biomarker.

PMID- 29189198
TI  - Multiple brown tumors - a rare presentation in the modern era?.
AB  - Chronic kidney disease (CKD) commonly evolves with disturbances in mineral and
      bone metabolism, currently defined as CKD-MBD. Management strategies have
      progressed over the years, but our knowledge regarding evaluation and treatment
      is still sparse. Herein, we describe a rare case of a hemodialysis patient with
      apparently fairly controlled hyperparathyroidism (HPTH), who developed multiple
      symptomatic brown tumors involving the scull, mandible, vertebrae, pelvis, and
      metacarpus. Parathyroidectomy allowed complete resolution of the bone lesions
      preventing disastrous consequences.?.

PMID- 29189199
TI  - Intrasellar cavernous hemangioma presenting as pituitary adenoma: A report of two
      cases and review of the literature.
AB  - Cavernous hemangioma in the sellar region is quite rare with only a handful of
      cases being reported in the English literature. Its clinical manifestations and
      imaging characteristics can mimic those of a pituitary adenoma. We report two
      cases of recurrent sellar lesions, both of which were clinically suspected of
      being pituitary adenomas but histologically confirmed as cavernous hemangiomas.
      The first case is of a 67-year-old female whose initial resection was diagnosed
      as "venous angioma". Neuroimaging performed 27 years later demonstrated
      significant growth of the lesion involving the right cavernous sinus and encasing
      the right internal carotid artery. The patient then underwent transsphenoidal
      endoscopic resection of the mass. At the time of the surgery, the lesion was
      noted to be quite vascular. The second case is a 48-year-old female who underwent
      emergency resection of a pituitary mass following an apoplectic event. On follow
      up 4 years later, the patient reported recurrence of galactorrhea, and MRI had
      demonstrated regrowth of the mass. She subsequently underwent subtotal resection
      of the mass. At the time of surgery, brisk bleeding was noted in the operative
      area. The above two cases demonstrate that cavernous hemangiomas in the sellar
      region can clinically and radiologically mimic pituitary adenoma and should be
      considered in the differential diagnosis of hemorrhagic sellar mass.?.

PMID- 29189200
TI  - Pituitary gland involvement by glioblastoma.

PMID- 29189202
TI  - Nanoscale control of plasmon-active metal nanodimer structures via
      electrochemical metal dissolution reaction.
AB  - Herein, we report the control of the optical properties of metal nanodimer
      structures using electrochemical metal dissolution reactions. The reaction rate
      could be precisely tuned by changing the electrochemical potential and, as a
      consequence, fine tuning of the size and gap distance of metal nanodimers was
      achieved as the functions of applied potential and polarization time. The
      observed linear correlation between the scattering intensity and charge resulting
      from nanostructure dissolutions suggested that the surface dissolution rate was
      0.30 nm min-1, corresponding to the surface dissolution of a single atomic layer
      per min. The present method can control the change in the volume of the
      structures, leading to the change in the gap distance of nanodimers at an atomic
      scale level.

PMID- 29189203
TI  - Proteomic characterization of human exhaled breath condensate.
AB  - To improve biomedical knowledge and to support biomarker discovery studies, it is
      essential to establish comprehensive proteome maps for human tissues and
      biofluids, and to make them publicly accessible. In this study, we performed an
      in-depth proteomics characterization of exhaled breath condensate (EBC), a sample
      obtained non-invasively by condensation of exhaled air that contains submicron
      droplets of airway lining fluid. Two pooled samples of EBC, each obtained from 10
      healthy donors, were processed using a straightforward protocol based on sample
      lyophilization, in-gel digestion and liquid chromatography tandem-mass
      spectrometry analysis. Two 'technical' control samples were processed in parallel
      to the pooled samples to correct for exogenous protein contamination. A total of
      229 unique proteins were identified in EBC among which 153 proteins were detected
      in both EBC pooled samples. A detailed bioinformatics analysis of these 153
      proteins showed that most of the proteins identified corresponded to proteins
      secreted in the respiratory tract (lung, bronchi). Eight proteins were salivary
      proteins. Our dataset is described and has been made accessible through the
      ProteomeXchange database (dataset identifier: PXD007591) and is expected to be
      useful for future MS-based biomarker studies using EBC as the diagnostic
      specimen.

PMID- 29189201
TI  - Time-gated detection of protein-protein interactions with transcriptional
      readout.
AB  - Transcriptional assays, such as yeast two-hybrid and TANGO, that convert
      transient protein-protein interactions (PPIs) into stable expression of
      transgenes are powerful tools for PPI discovery, screens, and analysis of cell
      populations. However, such assays often have high background and lose information
      about PPI dynamics. We have developed SPARK (Specific Protein Association tool
      giving transcriptional Readout with rapid Kinetics), in which proteolytic release
      of a membrane-tethered transcription factor (TF) requires both a PPI to deliver a
      protease proximal to its cleavage peptide and blue light to uncage the cleavage
      site. SPARK was used to detect 12 different PPIs in mammalian cells, with 5 min
      temporal resolution and signal ratios up to 37. By shifting the light window, we
      could reconstruct PPI time-courses. Combined with FACS, SPARK enabled 51 fold
      enrichment of PPI-positive over PPI-negative cells. Due to its high specificity
      and sensitivity, SPARK has the potential to advance PPI analysis and discovery.

PMID- 29189204
TI  - Optimized efficiency in InP nanowire solar cells with accurate 1D analysis.
AB  - Semiconductor nanowire arrays are a promising candidate for next generation solar
      cells due to enhanced absorption and reduced material consumption. However, to
      optimize their performance, time consuming three-dimensional (3D) opto
      electronics modeling is usually performed. Here, we develop an accurate one
      dimensional (1D) modeling method for the analysis. The 1D modeling is about 400
      times faster than 3D modeling and allows direct application of concepts from
      planar pn-junctions on the analysis of nanowire solar cells. We show that the
      superposition principle can break down in InP nanowires due to strong surface
      recombination in the depletion region, giving rise to an IV-behavior similar to
      that with low shunt resistance. Importantly, we find that the open-circuit
      voltage of nanowire solar cells is typically limited by contact leakage.
      Therefore, to increase the efficiency, we have investigated the effect of high
      bandgap GaP carrier-selective contact segments at the top and bottom of the InP
      nanowire and we find that GaP contact segments improve the solar cell efficiency.
      Next, we discuss the merit of p-i-n and p-n junction concepts in nanowire solar
      cells. With GaP carrier selective top and bottom contact segments in the InP
      nanowire array, we find that a p-n junction design is superior to a p-i-n
      junction design. We predict a best efficiency of 25% for a surface recombination
      velocity of 4500 cm s-1, corresponding to a non-radiative lifetime of 1 ns in p-n
      junction cells. The developed 1D model can be used for general modeling of axial
      p-n and p-i-n junctions in semiconductor nanowires. This includes also LED
      applications and we expect faster progress in device modeling using our method.

PMID- 29189205
TI  - High-density amorphous ice: nucleation of nanosized low-density amorphous ice.
AB  - The pressure dependence of the crystallization temperature of different forms of
      expanded high-density amorphous ice (eHDA) was scrutinized. Crystallization at
      pressures 0.05-0.30 GPa was followed using volumetry and powder x-ray
      diffraction. eHDA samples were prepared via isothermal decompression of very high
      density amorphous ice at 140 K to different end pressures between 0.07-0.30 GPa
      (eHDA0.07-0.3). At 0.05-0.17 GPa the crystallization line T x (p) of all eHDA
      variants is the same. At pressures  >0.17 GPa, all eHDA samples decompressed to
      pressures  <0.20 GPa exhibit significantly lower T x values than eHDA0.2 and
      eHDA0.3. We rationalize our findings with the presence of nanoscaled low-density
      amorphous ice (LDA) seeds that nucleate in eHDA when it is decompressed to
      pressures  <0.20 GPa at 140 K. Below ~0.17 GPa, these nanosized LDA domains are
      latent within the HDA matrix, exhibiting no effect on T x of eHDA<0.2. Upon
      heating at pressures  ?0.17 GPa, these nanosized LDA nuclei transform to ice IX
      nuclei. They are favored sites for crystallization and, hence, lower T x . By
      comparing crystallization experiments of bulk LDA with the ones involving
      nanosized LDA we are able to estimate the Laplace pressure and radius of ~0.3-0.8
      nm for the nanodomains of LDA. The nucleation of LDA in eHDA revealed here is
      evidence for the first-order-like nature of the HDA  ->  LDA transition,
      supporting water's liquid-liquid transition scenarios.

PMID- 29189206
TI  - Weakly spin-dependent band structures of antiferromagnetic perovskite LaMO3 (M  =
      Cr, Mn, Fe).
AB  - We investigate the spin-dependent electronic states of antiferromagnetic (AFM)
      lanthanum chromite (LaCrO3), lanthanum manganite (LaMnO3), and lanthanum ferrite
      (LaFeO3) using spin-polarized first-principles density functional theory with
      Hubbard U correction. The band structures are calculated for 15 types of their
      different AFM structures. It is verified for these structures that there is a
      very simple rule to identify which wave number [Formula: see text] exhibits spin
      splitting or degeneracy in the band structure. This rule uses the symmetry
      operations that map the up-spin atoms onto the down-spin atoms. The resulting
      spin splitting is very small for the most stable spin configuration of the most
      stable experimental structure. We discuss a plausible benefit of this
      characteristic, i.e. the direction-independence of the spin current, in electrode
      applications.

PMID- 29189207
TI  - PSF reconstruction for Compton-based prompt gamma imaging.
AB  - Compton-based prompt gamma (PG) imaging has been proposed for in vivo range
      verification in proton therapy. However, several factors degrade the image
      quality of PG images, some of which are due to inherent properties of a Compton
      camera such as spatial resolution and energy resolution. Moreover, Compton-based
      PG imaging has a spatially variant resolution loss. In this study, we investigate
      the performance of the list-mode ordered subset expectation maximization
      algorithm with a shift-variant point spread function (LM-OSEM-SV-PSF) model. We
      also evaluate how well the PG images reconstructed using an SV-PSF model
      reproduce the distal falloff of the proton beam. The SV-PSF parameters were
      estimated from simulation data of point sources at various positions. Simulated
      PGs were produced in a water phantom irradiated with a proton beam. Compared to
      the LM-OSEM algorithm, the LM-OSEM-SV-PSF algorithm improved the quality of the
      reconstructed PG images and the estimation of PG falloff positions. In addition,
      the 4.44 and 5.25 MeV PG emissions can be accurately reconstructed using the LM
      OSEM-SV-PSF algorithm. However, for the 2.31 and 6.13 MeV PG emissions, the LM
      OSEM-SV-PSF reconstruction provides limited improvement. We also found that the
      LM-OSEM algorithm followed by a shift-variant Richardson-Lucy deconvolution could
      reconstruct images with quality visually similar to the LM-OSEM-SV-PSF
      reconstructed images, while requiring shorter computation time.

PMID- 29189208
TI  - Extraneuraxial Hemangioblastoma: Clinicopathologic Features and Review of the
      Literature.
AB  - Extraneuraxial hemangioblastoma occurs in nervous paraneuraxial structures,
      somatic tissues, and visceral organs, as part of von Hippel-Lindau disease (VHLD)
      or in sporadic cases. The VHL gene plausibly plays a key role in the initiation
      and tumorigenesis of both central nervous system and extraneuraxial
      hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of
      the tumor growth are initially reviewed. The clinical criteria for the diagnosis
      of VHLD are summarized, with emphasis on the distinction of sporadic
      hemangioblastoma from the form fruste of VHLD (eg, hemangioblastoma-only VHLD).
      The world literature on the topic of extraneuraxial hemangioblastomas has been
      comprehensively reviewed with ~200 cases reported to date: up to 140
      paraneuraxial, mostly of proximal spinal nerve roots, and 65 peripheral, 15 of
      soft tissue, 6 peripheral nerve, 5 bone, and 39 of internal viscera, including 26
      renal and 13 nonrenal. A handful of possible yet uncertain cases from older
      literature are not included in this review. The clinicopathologic features of
      extraneuraxial hemangioblastoma are selectively presented by anatomic site of
      origin, and the differential diagnosis is emphasized in these subsets. Reference
      is made also to 10 of the authors' personal cases of extraneuraxial
      hemangioblastomas, which include 4 paraneuraxial and 6 peripheral (2 soft tissue
      hemangioblastoma and 4 renal).

PMID- 29189209
TI  - Temporal Trends in Difficult and Failed Tracheal Intubation in a Regional
      Community Anesthetic Practice.
AB  - BACKGROUND: When tracheal intubation is difficult or unachievable before surgery
      or during an emergent resuscitation, this is a critical safety event. Consensus
      algorithms and airway devices have been introduced in hopes of reducing such
      occurrences. However, evidence of improved safety in clinical practice related to
      their introduction is lacking. Therefore, we selected a large perioperative
      database spanning 2002 to 2015 to look for changes in annual rates of difficult
      and failed tracheal intubation. METHODS: Difficult (more than three attempts) and
      failed (unsuccessful, requiring awakening or surgical tracheostomy) intubation
      rates in patients 18 yr and older were compared between the early and late
      periods (pre- vs. post-January 2009) and by annual rate join-point analysis.
      Primary findings from a large, urban hospital were compared with combined
      observations from 15 smaller facilities. RESULTS: Analysis of 421,581 procedures
      identified fourfold reductions in both event rates between the early and late
      periods (difficult: 6.6 of 1,000 vs. 1.6 of 1,000, P < 0.0001; failed: 0.2 of
      1,000 vs. 0.06 of 1,000, P < 0.0001), with join-point analysis identifying two
      significant change points (2006, P = 0.02; 2010, P = 0.03) including a pre-2006
      stable period, a steep drop between 2006 and 2010, and gradual decline after
      2010. Data from 15 affiliated practices (442,428 procedures) demonstrated similar
      reductions. CONCLUSIONS: In this retrospective assessment spanning 14 yr (2002 to
      2015), difficult and failed intubation rates by skilled providers declined
      significantly at both an urban hospital and a network of smaller affiliated
      practices. Further investigations are required to validate these findings in
      other data sets and more clearly identify factors associated with their
      occurrence as clues to future airway management advancements. VISUAL ABSTRACT: An
      online visual overview is available for this article at
      http://links.lww.com/ALN/B635.

PMID- 29189212
TI  - Winner Announced.

PMID- 29189210
TI  - The Emergence of the Rehabilitative Strategy: The Driving Forces in the United
      States.
AB  - The aim of this essay was to show the impact that driving forces have had on the
      emergence of rehabilitation as a health strategy in the United States.
      Specifically, this essay (1) identifies the driving forces that have addressed
      the development of rehabilitation, (2) examines how the rehabilitative strategy
      has been driven by the driving forces through turning points and facilitators,
      and (3) identifies the barriers of each force against the development of
      rehabilitation. Critical and scoping review of the literature was conducted from
      the late 1910s until the end of the century. War, economy, the power of the
      state, and science were identified as the driving forces that led rehabilitation
      to become a health strategy complementing prevention, promotion, cure, and
      palliation. World War I and II played as a stimulus for rehabilitation, federal
      funding facilitated its development, acts, amendments, and governmental programs
      enabled its implementation, and the acknowledgment of physical medicine and
      rehabilitation as medical field contributed to its international recognition as
      health strategy. World Health Organization's International Classification of
      Functioning, Disability and Health is also identified as an emerging facilitator
      of rehabilitation. Based on the example of United States, this article closes
      with recommendations toward the implementation of rehabilitation as a health
      strategy in countries where so far this has not occurred.

PMID- 29189213
TI  - Blood pressure monitoring: theory and practice. European Society of Hypertension
      Working Group on Blood Pressure Monitoring and Cardiovascular Variability
      Teaching Course Proceedings.
AB  - The European Society of Hypertension (ESH) Working Group on Blood Pressure (BP)
      Monitoring and Cardiovascular Variability organized a Teaching Course on 'Blood
      Pressure Monitoring: Theory and Practice' during the 2017 ESH Meeting in Milan,
      Italy. This course performed by 11 international BP monitoring experts covered
      key topics of BP monitoring, including office BP measurement, ambulatory BP
      monitoring, home BP monitoring, ambulatory versus home BP, white-coat and masked
      hypertension, cuff use, and BP variability. This article presents a summary of
      the proceedings of the ESH BP Monitoring Teaching Course, including essential
      information, practical issues, and recommendations on the clinical application of
      BP monitoring methods, aiming to the optimal management of patients with
      suspected or diagnosed hypertension.

PMID- 29189214
TI  - Unadjusted Bivariate Two-Group Comparisons: When Simpler is Better.
AB  - Hypothesis testing involves posing both a null hypothesis and an alternative
      hypothesis. This basic statistical tutorial discusses the appropriate use,
      including their so-called assumptions, of the common unadjusted bivariate tests
      for hypothesis testing and thus comparing study sample data for a difference or
      association. The appropriate choice of a statistical test is predicated on the
      type of data being analyzed and compared. The unpaired or independent samples t
      test is used to test the null hypothesis that the 2 population means are equal,
      thereby accepting the alternative hypothesis that the 2 population means are not
      equal. The unpaired t test is intended for comparing dependent continuous
      (interval or ratio) data from 2 study groups. A common mistake is to apply
      several unpaired t tests when comparing data from 3 or more study groups. In this
      situation, an analysis of variance with post hoc (posttest) intragroup
      comparisons should instead be applied. Another common mistake is to apply a
      series of unpaired t tests when comparing sequentially collected data from 2
      study groups. In this situation, a repeated-measures analysis of variance, with
      tests for group-by-time interaction, and post hoc comparisons, as appropriate,
      should instead be applied in analyzing data from sequential collection points.
      The paired t test is used to assess the difference in the means of 2 study groups
      when the sample observations have been obtained in pairs, often before and after
      an intervention in each study subject. The Pearson chi-square test is widely used
      to test the null hypothesis that 2 unpaired categorical variables, each with 2 or
      more nominal levels (values), are independent of each other. When the null
      hypothesis is rejected, 1 concludes that there is a probable association between
      the 2 unpaired categorical variables. When comparing 2 groups on an ordinal or
      nonnormally distributed continuous outcome variable, the 2-sample t test is
      usually not appropriate. The Wilcoxon-Mann-Whitney test is instead preferred.
      When making paired comparisons on data that are ordinal, or continuous but
      nonnormally distributed, the Wilcoxon signed-rank test can be used. In analyzing
      their data, researchers should consider the continued merits of these simple yet
      equally valid unadjusted bivariate statistical tests. However, the appropriate
      use of an unadjusted bivariate test still requires a solid understanding of its
      utility, assumptions (requirements), and limitations. This understanding will
      mitigate the risk of misleading findings, interpretations, and conclusions.

PMID- 29189216
TI  - Factors Contributing to Memory of Acute Pain in Older Adults Undergoing Planned
      and Unplanned Hip Surgery.
AB  - OBJECTIVES: Previous research on pain memory provides inconsistent evidence about
      the accuracy of pain recall, and few studies have attempted to examine broad
      affective and contextual contributions to this phenomenon. The present research
      aimed to determine the accuracy of postoperative pain recall after 3 months, with
      respect to the context of the surgery and the congruence of affective states
      concurrent with the initial experience and its recall. The study also aimed to
      identify predictors of remembered pain by analyzing a range of sensory,
      cognitive, and affective factors. METHODS: Older adults, undergoing planned
      (N=40) and unplanned hip surgery (N=31), were enrolled in this prospective study
      to investigate their presurgery, postsurgery, and delayed ratings of expected,
      experienced, and recalled pain intensity and unpleasantness, state anxiety, and
      positive and negative affect. RESULTS: Memory of postoperative pain was found to
      be accurate, regardless of the context of the surgery. Affective states in the
      postoperative period were congruent with those during pain recall. The study also
      revealed that in planned surgery context, remembered pain was predicted by
      experienced postoperative pain, cognitive functions, positive and negative
      affect; whereas in unplanned surgery context its significant predictors included
      age, anxiety, and negative and positive affect. DISCUSSION: The results of this
      study suggest that older orthopedic patients remember postoperative pain
      correctly after 3 months and that mood dependence effect may contribute to memory
      of pain. Pain recall after planned surgery seems to depend mainly on the actual
      experience, while following unplanned surgery it depends on affective factors.
      Present findings contribute to knowledge about pain memory in older adults and
      have implications for patients' recovery and best practice in perioperative
      hospital care.

PMID- 29189215
TI  - Lateral Transperitoneal Adrenalectomy Versus Posterior Retroperitoneoscopic
      Adrenalectomy for Benign Adrenal Gland Disease: Randomized Controlled Trial at a
      Single Tertiary Medical Center.
AB  - OBJECTIVE: The aim of this study was to compare the surgical outcomes of lateral
      transperitoneal adrenalectomy (LTA) and posterior retroperitoneoscopic
      adrenalectomy (PRA) for benign adrenal tumor. BACKGROUND: Although LTA is the
      standard treatment for benign adrenal gland tumor, PRA has recently gained
      popularity. Studies comparing the surgical outcomes of the 2 approaches have
      reported conflicting findings and thus it remains unclear which approach is
      superior. METHODS: This trial was conducted between September 2012 and February
      2016. Patients were randomized to either LTA or PRA groups in a 1:1 ratio using
      web-based randomization. The primary outcome was operative time, and the
      secondary outcomes were blood loss, intraoperative hemodynamic stability,
      postoperative pain, recovery of bowel movement, and complication rates. This
      trial was registered with ClincalTrials.gov, number NCT01676025. RESULTS: A total
      of 83 patients were randomly assigned to the LTA group (n = 42) or the PRA group
      (n = 41). Median follow-up was 31.3 months. The mean operative times of LTA and
      PRA were comparable (59.7 +/- 18.6 vs 67.6 +/- 28.7 minutes, P = 0.139). Logistic
      regression analysis showed that male sex [odds ratio (OR) = 4.20] and
      pheochromocytoma (OR = 5.06) were associated with an operative time >=60 minutes.
      There were no differences in the secondary outcomes between the groups. One
      patient in the PRA group required open conversion. CONCLUSION: Both LTA and PRA
      were performed safely with similar operative outcomes, and thus are comparable
      options for the treatment of benign adrenal gland tumor.

PMID- 29189217
TI  - Anterior Cutaneous Nerve Entrapment Syndrome in Children: A Prospective
      Observational Study.
AB  - OBJECTIVE: Anterior cutaneous nerve entrapment syndrome (ACNES) is often an
      overlooked cause of abdominal pain. Data for pediatric patients, especially with
      regard to the treatment modalities are scarce. The aim of this study was to
      present a treatment modality of ACNES with combined local subfascial anesthetic
      and corticosteroid injection in a prospectively collected cohort of pediatric
      patients. METHODS: This was a prospective observational long-term study that
      included pediatric patients who were diagnosed with ACNES in a tertiary care
      pediatric center and who were followed-up for at least 12 months (median: 1.7 y;
      range: 1 to 2.7 y). All children were treated by ultrasound-guided subfascial
      injection of 40 mg 1% lidocaine and 4 mg dexamethasone into the rectus abdominis
      muscle in the place of the most severe pain (trigger point infiltration).
      RESULTS: The study included 38 children (28, 73.7% female; median age: 15 y). The
      majority of patients had pain in the lower right abdominal quadrant and were
      diagnosed in a median of 6 (range: 0.5 to 50) months after symptoms started.
      Overall, 24 (63%) patients achieved sustained symptom-free remission after a
      median of 1 (mean: 1.6; range: 1 to 5) trigger point infiltration during the
      first treatment session. Five (13%) children were surgically treated because of a
      lack of long-term response. Children who were surgically treated required a
      higher number of block applications during the first session of treatment,
      compared with children who were successfully treated conservatively. DISCUSSION:
      ACNES in children can be successfully treated by a combined local subfascial
      anesthetic and corticosteroid trigger point infiltration.

PMID- 29189218
TI  - Adjacent Level Degeneration: Bryan Total Disc Arthroplasty Versus Anterior
      Cervical Discectomy and Fusion.
AB  - STUDY DESIGN: Prospective randomized, 2-center, clinical trial. OBJECTIVE: To
      prospectively compare adjacent level degeneration between the Bryan Cervical Disc
      Prosthesis and anterior cervical discectomy and fusion (ACDF), and assess the
      reliability of our measurements utilizing a method not previously described.
      SUMMARY OF BACKGROUND DATA: ACDF is a reliable and proven procedure for the
      treatment of radiculopathy and/or myelopathy. Despite a successful track record
      several limitations including adjacent segment degeneration/disease, loss of
      viscoelastic disc properties, perioperative immobilization, graft site morbidity,
      pseudarthrosis, and plating complications have been identified. An original
      driving force and theoretical basis for total disc arthroplasty was prevention of
      adjacent level degeneration. MATERIALS AND METHODS: Seventy-nine patients were
      enrolled and followed prospectively at 2 centers in a multicenter, Food and Drug
      Administration Investigational Device Exemption trial for the Bryan Cervical Disc
      arthroplasty. Neutral lateral radiographs were obtained preoperatively and
      postoperatively, and at 1-, 2-, 4-, and out to 7-year follow-up after surgery.
      The cephalad, adjacent level above the blinded procedure level was analyzed for
      all patients and time points by measuring the anteroposterior distance and the
      vertical disc height. A ratio was created using disc height/anteroposterior
      distance. RESULTS: Seventy patients (Bryan Cervical Disc N=34 and ACDF N=36) met
      inclusion criteria. Both fusion and arthroplasty groups showed a significant
      (P=0.001) decrease in disc height over time, indicative of adjacent level
      degeneration. Overall change in disc height between groups was not significantly
      different. Using our measurement technique, the overall interreviewer reliability
      was good [intrareviewer correlation coefficients (95% confidence interval)=0.77
      (0.55-0.85)] and intrareviewer reliability was excellent [0.93 (0.91-0.94) and
      0.85 (0.81-0.87)]. CONCLUSIONS: Adjacent level degeneration occurs in a similar
      manner in both the ACDF and total disc arthroplasty group. Our measurement
      technique is reliable and to the best of our knowledge not previously reported in
      the literature.

PMID- 29189219
TI  - Family Caregivers Need Our Help-And Now It's the Law.
AB  - The CARE Act mandates preparation and teaching prior to hospital discharge.

PMID- 29189220
TI  - Social Determinants of Health: The Role of Nursing.
AB  - A call to action for research, education, and collaboration.

PMID- 29189221
TI  - Nurses' Use of On-the-Job Workarounds.

PMID- 29189222
TI  - Nurses' Use of On-the-Job Workarounds.

PMID- 29189223
TI  - Palliative Care for Advanced Dementia.

PMID- 29189224
TI  - Staying Professional on Social Media.

PMID- 29189225
TI  - The Need to Improve Student Writing.

PMID- 29189226
TI  - Women in Rural America Are Losing Hospital-Based Obstetric Services.
AB  - Isolated counties with low populations are most affected.

PMID- 29189227
TI  - Repeal of the ACA Could Lead to RN Job Cuts.
AB  - Women, who make up 90% of the profession, would bear the brunt.

PMID- 29189229
TI  - Study Finds Overall Prostate Cancer Mortality Decreases with PSA Screening.
AB  - But questions remain about how best to screen so the benefits outweigh the harms.

PMID- 29189231
TI  - Updated Pediatric Blood Pressure Guidelines.
AB  - Simplified guidance may ease management of high blood pressure in children.

PMID- 29189233
TI  - Nurses on the ground in Puerto Rico.

PMID- 29189235
TI  - World Health Roundup.

PMID- 29189234
TI  - Nurses rally in Illinois for legislation to end workplace violence.

PMID- 29189236
TI  - When Parents Disappear Behind Bars.
AB  - Life can be challenging for the millions of children left behind.

PMID- 29189239
TI  - New Indication for Ibrutinib.

PMID- 29189240
TI  - New Antibiotic for Complicated Urinary Tract Infections.

PMID- 29189244
TI  - Teaching Family Caregivers to Assist Safely with Mobility.
AB  - : This article is part of a series, Supporting Family Caregivers: No Longer Home
      Alone, published in collaboration with the AARP Public Policy Institute. Results
      of focus groups, conducted as part of the AARP Public Policy Institute's No
      Longer Home Alone video project, supported evidence that family caregivers aren't
      given the information they need to manage the complex care regimens of family
      members. This series of articles and accompanying videos aims to help nurses
      provide caregivers with the tools they need to manage their family member's
      health care at home.The articles in this new installment of the series explain
      principles for promoting safe mobility that nurses should reinforce with family
      caregivers. Each article also includes an informational tear sheet-Information
      for Family Caregivers-that contains links to instructional videos. To use this
      series, nurses should read the article first, so they understand how best to help
      family caregivers, and then encourage the caregivers to watch the videos and ask
      questions. For additional information, see Resources for Nurses.

PMID- 29189245
TI  - Rethinking Standard Disaster Planning for Nursing Homes.

PMID- 29189246
TI  - CNAs Frequently Use Gloves Inappropriately.

PMID- 29189247
TI  - SSRI and SNRI Use in Children and Adolescents Leads to Small Benefits, Safety
      Concerns.

PMID- 29189248
TI  - Long-Term Analysis of Postmenopausal Estrogen Use Finds no Increased Mortality.

PMID- 29189249
TI  - A Nurse-Led Ultrasound-Enhanced Vascular Access Preservation Program.
AB  - : Insertion of peripheral iv catheters is a common practice in medical-surgical
      care settings. The frequency with which attempts are made to insert catheters
      causes rapid peripheral vessel depletion (a reduction in the number of usable
      veins), leading to the overuse of unnecessary central line catheters. Reducing
      central line-associated bloodstream infections is a national health care
      priority. In this quality improvement report, the authors describe the
      implementation of a nurse-led vascular access preservation program using
      ultrasound technology as a method to reduce the use of nonessential peripherally
      inserted central catheters.

PMID- 29189250
TI  - The Gaming of U.S. Health Care.
AB  - Elisabeth Rosenthal's new book reveals how the system's dysfunctional economics
      harms us.

PMID- 29189251
TI  - Reconsidering Antibiotic Resistance.
AB  - What if our prescribing practices are wrong?

PMID- 29189252
TI  - Home for Christmas: Flight Nursing and the Symbols of Hope.
AB  - Updated several times a week with posts by a wide variety of authors, AJN's blog
      Off the Charts allows us to provide more timely-and often more personal
      perspectives on professional, policy, and clinical issues. Best of the Blog will
      be a regular column to draw the attention of AJN readers to posts we think
      deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com.

PMID- 29189253
TI  - Probiotics in Preventing Acute Upper Respiratory Tract Infections.
AB  - Editor's note: This is a summary of a nursing care-related systematic review from
      the Cochrane Library. For more information, see http://nursingcare.cochrane.org.

PMID- 29189255
TI  - Shut Up and Let the Women Speak.
AB  - An NP remembers sage advice from a Dominican priest.

PMID- 29189256
TI  - Enteric Pathologic Manifestations of Alpha-Synucleinopathies.
AB  - BACKGROUND: Gastrointestinal (GI) symptoms are common in Parkinson disease (PD),
      often preceding neurological manifestations; however, early diagnostic utility of
      GI biopsies remains controversial. Studies suggest aberrant deposition of alpha
      synuclein (alpha-syn) follows step-wise progression in central nervous system
      though histologic interpretation of normal and aberrant staining patterns have
      shown variable results. This study examines whether GI alpha-syn mRNA expression
      combined with standard alpha-syn immunohistochemical staining enhance the role of
      GI biopsy in PD. MATERIALS AND METHODS: Four groups were examined, including
      pediatric (21) and adult control patients (18), PD clinic patients (17), and
      pathologically confirmed PD cases from hospital archives (16). Enteric nervous
      system alpha-syn staining was evaluated by immunohistochemistry in 33 PD and 39
      controls. alpha-Syn mRNA levels were compared between patient groups using
      quantitative polymerase chain reaction and stomach and colon levels in PD.
      RESULTS: PD patients had Lewy bodies (LB) and diffuse neuronal alpha-syn
      staining. GI tissues from elderly controls, children, and young adults exhibited
      diffuse positivity. LB were limited to PD. Myenteric plexus immunoreactivity
      varied in different regions. Widespread staining was noted within stomach and
      colon. Immunoreactivity was present within esophagus, appendix, and small bowel.
      alpha-Syn mRNA expression was highest in PD; however, levels varied between
      proximal and distal GI tract. CONCLUSIONS: alpha-Syn is normally present within
      young and elderly enteric nervous system; furthermore, while alpha-syn mRNA is
      always detectable, levels are highest and most variable in PD. This suggests that
      enteric alpha-syn may be altered in neurodegenerative disease. The presence of LB
      in the GI tract, not solely alpha-syn expression, may prove useful,
      distinguishing neurodegenerative disease patients from normal controls.

PMID- 29189257
TI  - The Royal College of Pathologists of Australasia Quality Assurance Program:
      Immunohistochemistry Breast Marker Audit Overview 2005-2015.
AB  - The Royal College of Pathologists of Australasia Quality Assurance Program
      (RCPAQAP) Anatomical Pathology provides a comprehensive External Quality
      Assurance (EQA) exercise to review the reporting of immunohistochemistry (IHC)
      and in-situ hybridization (ISH) breast markers through an audit of clinical
      results. The aim of this exercise was to provide information regarding the
      quality of breast marker testing within clinical laboratories from 2005 to 2015.
      This comprehensive audit included estrogen, progesterone, and HER2 marker
      reporting. This was an important quality assurance activity established in
      response to ongoing difficulties experienced in laboratories in this area of
      testing.

PMID- 29189258
TI  - The Use of Smoothelin and Other Antibodies in the Diagnosis of Uterine and Soft
      Tissue Smooth Muscle Tumors.
AB  - Smoothelin is a cytoplasmic protein expressed in differentiated smooth muscle
      cells. Immunohistochemical evaluation of smoothelin has previously been reported
      in gastrointestinal (GI) smooth muscle tumors, but has yet to be studied in
      smooth muscle tumors of uterine and other soft tissue origin. DOG1 expression is
      reported to be specific for GI stromal tumors; however, variable expression has
      been reported in leiomyosarcomas (LMS) depending on site of origin.
      Overexpression of p16 is common in LMS of uterine and other sites of origin, but
      has not been correlated with tumor grade. This study explores the differential
      expression of these markers, as well as caldesmon, in LMS cases to assess
      diagnostic utility. Using tissue microarrays and cases from Tulane Medical Center
      and Medical College of Wisconsin, expression of smoothelin, DOG1, caldesmon, and
      p16 was evaluated by immunohistochemistry in 87 cases of LMS. The cases were
      subdivided by location of origin into uterine (N=31) and nonuterine (N=56) with
      10 of the nonuterine of GI origin, as well as by grade into low grade (N=27) and
      intermediate and high grade (N=60). Differential expression among different
      grades and locations was evaluated. The same markers were evaluated in atypical
      leiomyoma cases (N=4) and 1 smooth muscle tumor of uncertain malignant potential
      case (N=1). Smoothelin expression was also assessed in 20 benign uterine
      leiomyomas. Weak DOG1 expression is rare but possible in extrauterine LMS.
      Expression of p16 is common in both uterine and extrauterine LMS, and more
      frequent in higher grades. Expression of smoothelin in this study differed
      depending on tumor type, grade, and site of origin. All leiomyomas and most
      atypical leiomyomas showed cytoplasmic positivity for smoothelin, whereas only 5%
      of LMS had cytoplasmic expression. The study suggests smoothelin may be
      downregulated in the cytoplasm of malignant smooth muscle tumor cells and may
      serve as a supportive aid in the distinction of LMS from benign smooth muscle
      tumors in cases where it is difficult by morphology alone.

PMID- 29189259
TI  - Histologic Features Do Not Reliably Predict Mismatch Repair Protein Deficiency in
      Colorectal Carcinoma: The Results of a 5-Year Prospective Evaluation.
AB  - Most major professional medical organizations advocate universal screening for
      Lynch syndrome in colorectal carcinoma; however, some allow for a selective
      screening approach based on clinicopathologic factors including assessment of
      histologic features of mismatch repair protein deficiency (MMRD). We performed a
      prospective evaluation for histopathologic features of MMRD in colorectal
      carcinomas that underwent universal screening for Lynch syndrome to evaluate the
      ability of histology to predict MMRD. In total, 947 resected colorectal
      carcinomas over a 5-year period were prospectively analyzed for histologic
      features of MMRD and for DNA mismatch repair protein abnormalities. Histologic
      features of MMRD were reported as present in 281 of 947 (30%) tumors with only
      109 (39%) cases demonstrating MMRD by immunohistochemistry. Histologic features
      of MMRD had a sensitivity of 74% [95% confidence interval (CI), 66%-80%],
      specificity of 78% (95% CI, 75%-81%), positive predictive value of 39% (95% CI,
      32%-44%), and negative predictive value of 94% (95% CI, 92%-96%). Histologic
      features of MMRD in left colon/rectal tumors had a significantly lower
      sensitivity of 56% (95% CI, 41%-77%) compared with right colon tumors (P=0.02).
      Histologic rereview identified that tumor-infiltrating lymphocytes (TILs) were
      most likely to be incorrectly reported as absent, and 72% of cases incorrectly
      assessed as lacking TILs demonstrated MMRD by immunohistochemistry. We
      demonstrate that histologic features of MMRD do not reliably predict the presence
      of MMRD by immunohistochemistry. Interpretative errors in the assessment of
      histologic features of MMRD occur, particularly for TILs and in tumors of the
      left colon/rectum.

PMID- 29189260
TI  - Different Expression of Aldehyde Dehydrogenases 1A1 and 2 in Oral Leukoplakia
      With Epithelial Dysplasia and in Oral Squamous Cell Carcinoma.
AB  - Oral potentially malignant disorders (OPMD) may develop malignant characteristics
      and transform into oral squamous cell carcinoma (OSCC) in a range of 1% to 2% of
      cases. Chronic alcohol consumption is associated with carcinogenesis, but its
      mechanism has not yet been fully elucidated. ALDH1A1 and 2, isoenzymes
      responsible for aldehyde oxidation involved in ethanol metabolism may be
      associated with the development of malignant head and neck neoplasms. The aim of
      this study was to analyze the expression of ALDH1A1 and ALDH2 in oral leukoplakia
      with epithelial dysplasia (OLP) and OSCC. A retrospective study was conducted on
      27 cases of OLP and 30 cases of OSCC. Clinical data were obtained from medical
      records, and all cases were classified as mild, moderate, and severe for OLP, and
      well-differentiated, moderately differentiated, or poorly differentiated for OSCC
      cases. The ALDH1A1 and ALDH2 expression in OLP and OSCC was evaluated by the
      immunohistochemical technique. There was predominance of the male sex, in both
      OLP and OSCC cases. Oral tongue was the most affected site in both groups. OLP
      showed positive protein expression of ALDH1A1 in all cases, both basal and
      suprabasal epithelial layers, whereas ALDH2 showed less protein expression. In
      OSCC, the immunohistochemical reaction for ALDH1A1 expression was negative in
      70%, whereas ALDH2 expression was positive in all cases. This study demonstrated
      the gradual loss of ALDH1A1 expression in OSCC in comparison with OLP, and the
      increased ALDH2 expression in OSCC.

PMID- 29189261
TI  - Collaborative Multi-institutional Experience in Comparing PD-L1
      Immunohistochemistry Assays: Concordance of SP142 and 22C3 Immunoreactivity.

PMID- 29189262
TI  - Novel Technology to Assess Programmed Death-Ligand 1 Expression by Multiplex
      Immunofluorescence and Image Analysis.

PMID- 29189263
TI  - B7-H4 is Inversely Correlated With T-Cell Infiltration in Clear Cell but Not
      Serous or Endometrioid Ovarian Cancer.
AB  - B7-H4, a tumor-associated cell surface protein, is expressed in endometrioid
      (EM), serous (SE), and clear cell (CC) ovarian carcinomas. Prior in vitro studies
      from other groups indicated that elevated B7-H4 expression by tumor cells blocks
      T-cell activation; therefore, it had been postulated to play a role in shielding
      cancer cells from immune surveillance and averting apoptotic programs. To test
      the validity of these hypotheses, the present study was designed to compare the
      immunohistochemical staining intensity of B7-H4 in tumor cells of ovarian cancers
      with the number of tumor-infiltrating T cells and macrophages and with the levels
      of caspase-3 staining in apoptotic debris. Serial tissue sections from EM, SE,
      and CC carcinomas were analyzed across representative cross-sections of tumor
      resection specimens, demonstrating different levels of B7-H4 expression, highest
      in CC cancers. B7-H4 staining in CC tissue sections was significantly correlated
      with the number of CD3, CD4, and CD8 tumor-infiltrating T cells and with the
      number of CD14 tumor-infiltrating macrophages, but was not significantly related
      to caspase-3 staining. These results support the concept that high levels of B7
      H4 expression are inversely correlated with tumor T-cell infiltration and with
      CD14-labeled macrophages but not caspase-3 expression in CC carcinomas. We did
      not, however, find clear evidence of a relationship between the lower levels of
      B7-H4 seen in EM and SE carcinomas and T cell or macrophage infiltration. Thus,
      high levels of B7-H4, as seen in CC carcinomas, is associated with decreased
      tumor infiltration by T cells and macrophages but the lower levels of expression,
      as observed in EM and SE carcinomas, appear less likely to play an effective role
      in protection from immune surveillance. Furthermore, we found no evidence of a
      correlation between B7-H4 expression and apoptosis. These findings highlight the
      importance of further investigation of B7-H4 as an immunomodulatory protein, to
      support the development of novel therapeutic interventions for improved efficacy
      of treatments for CC carcinoma.

PMID- 29189264
TI  - Dendritic Cell Markers and PD-L1 are Expressed in Mediastinal Gray Zone Lymphoma.
AB  - AIMS: Mediastinal gray zone lymphoma (MGZL) is a rare entity with morphologic,
      immunophenotypic, and genetic features intermediate between classic Hodgkin
      lymphoma (CHL) and primary mediastinal large B-cell lymphoma (PMBL). It is
      challenging to differentiate from CHL and PMBL. A specific dendritic cell gene
      expression profile can distinguish CHL and MGZL from PMBL. We hypothesized that
      the dendritic markers fascin and CD123 may be helpful in distinguishing MGZL from
      CHL and PMBL. We also investigated programmed death-ligand 1 (PD-L1) expression
      in MGZL, which may have therapeutic significance in this difficulty to treat
      tumor. METHODS: Representative sections from 89 CHL, 20 PMBL, and 7 MGZL cases
      were stained for fascin, CD123, and PD-L1, and scored on a scale from 0 to 3+.
      Most (71%) MGZLs stained for CD123, as well as some (23%) CHLs, and few (11%)
      PMBLs. All MGZLs stained for fascin, as well as most (90%) CHLs, and
      approximately half (53%) of the PMBLs. PD-L1 was positive in all MGZLs, most
      (77%) CHLs and most (66%) PMBLs. CONCLUSIONS: Our study is the first to show
      CD123 is positive in a subset of formalin-fixed, paraffin-embedded MGZLs and
      CHLs, in contrast to PMBL which is largely negative. Staining for fascin was not
      significantly different between the lymphomas, but was less likely to be positive
      in PMBL. These findings suggest a role for CD123 and fascin in supporting
      diagnoses of MGZL and CHL, and in ruling out PMBL. By immunohistochemistry, PD-L1
      is positive in MGZL, pointing to its therapeutic potential.

PMID- 29189265
TI  - Development of a Diagnostic Programmed Cell Death 1-Ligand 1 Immunohistochemistry
      Assay for Nivolumab Therapy in Melanoma.
AB  - Nivolumab is a monoclonal antibody that blocks the interaction between programmed
      cell death 1 (PD1) and programmed cell death 1-ligand 1 (PD-L1), resulting in
      enhanced antitumor activity by the immune system. Nivolumab is currently approved
      by the US Food and Drug Administration (FDA) for melanoma, non-small cell lung
      cancer (NSCLC), renal cell carcinoma, classical Hodgkin lymphoma, squamous cell
      carcinoma of the head and neck, and urothelial carcinoma. PD-L1 IHC 28-8 pharmDx
      is FDA-approved as a complementary diagnostic for immunohistochemical (IHC)
      detection of PD-L1 in non-squamous NSCLC and melanoma. We report validation of PD
      L1 IHC 28-8 pharmDx for PD-L1 detection on formalin-fixed, paraffin-embedded
      human melanoma specimens using Autostainer Link 48. A prevalence assessment of
      104 melanoma specimens indicated that PD-L1 was detected across the full
      expression level range (0% to 100% of tumor cells). Assay robustness and
      precision studies were conducted at Agilent Technologies, with additional
      reproducibility studies performed at 3 external laboratories. Precision studies
      evaluated at >=1% and >=5% expression levels revealed a range of average negative
      agreement from 89.5%, 95% CI (83.2, 93.6) to 100%, 95% CI (97.3, 100), and
      average positive agreement from 85.5%, 95% CI (77.6, 90.9) to 100%, 95% CI (97.9,
      100). For external reproducibility, precise results were obtained. These results
      demonstrate PD-L1 IHC 28-8 pharmDx is a precise, robust, and reproducible assay
      for determining PD-L1 expression in melanoma. This is the first PD-L1 IHC test to
      receive FDA approval as a complementary diagnostic in melanoma patients whereby
      positive PD-L1 expression is correlated with the magnitude of nivolumab treatment
      effect.

PMID- 29189266
TI  - Epidural Space Identification With Loss of Resistance Technique for Epidural
      Analgesia During Labor: A Randomized Controlled Study Using Air or Saline-New
      Arguments for an Old Controversy.
AB  - BACKGROUND: The best technique to identify the epidural space for labor analgesia
      is still unclear despite the publication of various randomized controlled studies
      and meta-analyses. Our aim was to assess the superiority of the saline loss of
      resistance (SLOR) technique over the air loss of resistance (ALOR) technique with
      respect to the quality of the block. METHODS: Consenting parturients admitted to
      our obstetric suite for spontaneous or induced labor were randomized to receive
      epidural analgesia using either the ALOR or SLOR technique. Our primary outcome
      was to compare the impact of the SLOR and ALOR technique on pain score
      improvement measured 30 minutes after administration of epidural block. Our
      secondary outcomes included the density of motor blockade and analgesic efficacy
      measured at 30 minutes. Primary and secondary outcomes were compared using the
      Student t test and Mann-Whitney U test. Statistical significance was set at P <
      .017 for primary and secondary outcomes, considering Bonferroni correction for
      multiple comparisons. Other comparisons were considered exploratory. RESULTS:
      Four hundred parturients were included; 24 were excluded from the final analysis.
      After 30 minutes, pain score reduction (ALOR, 4.7 +/- 2.9/10; SLOR, 4.9 +/-
      3.0/10; P = .49), motor block (ALOR, 1.4 +/- 0.8; SLOR, 1.3 +/- 0.8; P = .27),
      and efficacy of the block (ALOR, 1.0 +/- 0.7; SLOR, 1.0 +/- 0.6; P = .87) did not
      differ significantly between groups. CONCLUSIONS: Pain score reduction after 30
      minutes and onset of the block were not affected by the technique used to locate
      the epidural space.

PMID- 29189267
TI  - In Response.

PMID- 29189268
TI  - Risk of Cognitive Impairment by Sleep-Disordered Breathing.

PMID- 29189269
TI  - Comparison of Transcranial Doppler and Ultrasound-Tagged Near Infrared
      Spectroscopy for Measuring Relative Changes in Cerebral Blood Flow in Human
      Subjects.
AB  - BACKGROUND: Currently, no reliable method exists for continuous, noninvasive
      measurements of absolute cerebral blood flow (CBF). We sought to determine how
      changes measured by ultrasound-tagged near-infrared spectroscopy (UT-NIRS)
      compare with changes in CBF as measured by transcranial Doppler (TCD) in healthy
      volunteers during profound hypocapnia and hypercapnia. METHODS: Ten healthy
      volunteers were monitored with a combination of TCD, UT-NIRS (c-FLOW, Ornim
      Medical), as well as heart rate, blood pressure, end-tidal PCO2 (PEtCO2), end
      tidal O2, and inspired O2. Inspired CO2 and minute ventilation were controlled to
      achieve 5 stable plateau goals of EtCO2 at 15-20, 25-30, 35-40, 45-50, and 55-60
      mm Hg, for a total of 7 measurements per subject. CBF was assessed at a steady
      state, with the TCD designated as the reference standard. The primary analysis
      was a linear mixed-effect model of TCD and UT-NIRS flow with PEtCO2, which
      accounts for repeated measures. Receiver operating characteristic curves were
      determined for detection of changes in CBF. RESULTS: Hyperventilation (nadir
      PEtCO2 17.1 +/- 2.4) resulted in significantly decreased mean flow velocity of
      the middle cerebral artery from baseline (to 79% +/- 22%), but not a consistent
      decrease in UT-NIRS cerebral flow velocity index (n = 10; 101% +/- 6% of
      baseline). Hypercapnia (peak PEtCO2 59.3 +/- 3.3) resulted in a significant
      increase from baseline in both mean flow velocity of the middle cerebral artery
      (153% +/- 25%) and UT-NIRS (119% +/- 11%). Comparing slopes versus PEtCO2 as a
      percent of baseline for the TCD (1.7% [1.5%-2%]) and UT-NIRS (0.4% [0.3%-0.5%])
      shows that the UT-NIRS slope is significantly flatter, P < .0001. Area under the
      receiver operating characteristic curve was significantly higher for the TCD than
      for UT-NIRS, 0.97 (95% confidence interval, 0.92-0.99) versus 0.75 (95%
      confidence interval, 0.66-0.82). CONCLUSIONS: Our data indicate that UT-NIRS
      cerebral flow velocity index detects changes in CBF only during hypercarbia but
      not hypocarbia in healthy subjects and with much less sensitivity than TCD.
      Additional refinement and validation are needed before widespread clinical
      utilization of UT-NIRS.

PMID- 29189270
TI  - Not All Calcium Formulations Are Alike.

PMID- 29189271
TI  - Low- Versus High-Chloride Content Intravenous Solutions for Critically Ill and
      Perioperative Adult Patients: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: To assess whether use of low-chloride solutions in unselected
      critically ill or perioperative adult patients for maintenance or resuscitation
      reduces mortality and renal replacement therapy (RRT) use when compared to high
      chloride fluids. METHODS: Systematic review and meta-analysis with random-effects
      inverse variance model. PubMed, Cochrane library, EMBASE, LILACS, and Web of
      Science were searched from inception to October 2016. Published and unpublished
      randomized controlled trials in any language that enrolled critically ill and/or
      perioperative adult patients and compared a low- to a highchloride solution for
      volume maintenance or resuscitation. The primary outcomes were mortality and RRT
      use. We conducted trial sequential analyses and assessed risk of bias of
      individual trials and the overall quality of evidence. Fifteen trials with 4067
      patients, most at low risk of bias, were identified. Of those, only 11 and 10
      trials had data on mortality and RRT use, respectively. A total of 3710 patients
      were included in the mortality analysis and 3724 in the RRT analysis. RESULTS: No
      statistically significant impact on mortality (odds ratio, 0.90; 95% confidence
      interval, 0.69-1.17; P = .44; I = 0%) or RRT use (odds ratio, 1.12; 95%
      confidence interval, 0.80-1.58; P = .52; I = 0%) was found. Overall quality of
      evidence was low for both primary outcomes. Trial sequential analyses highlighted
      that the sample size needed was much larger than that available for properly
      powered outcome assessment. CONCLUSIONS: The current evidence on low- versus high
      chloride solutions for unselected critically ill or perioperative adult patients
      demonstrates no benefit, but suffers from considerable imprecision. We noted a
      limited exposure volume for study fluids and a relatively low risk of the
      populations in each study. Together with the relatively small pooled sample size,
      these data leave us underpowered to detect potentially important differences.
      Results from well-conducted, adequately powered randomized controlled trials
      examining sufficiently large fluid exposure are necessary.

PMID- 29189272
TI  - In Response.

PMID- 29189273
TI  - Two-Year Follow-up Survey: Views of US Anesthesiologists About Health Care Costs
      and Future Practice Roles.
AB  - Anesthesiologists' perspectives on US health care finance reform are increasingly
      germane to recent policy reforms. The aim of this follow-up survey was to examine
      how anesthesiologists' views of health care costs and future practice roles have
      changed since 2014. Six thousand randomly chosen active members of the American
      Society of Anesthesiologists were again surveyed and were also asked several new
      questions regarding specialties and perioperative management. Results showed an
      increase in self-reported understanding of the perioperative surgical home.
      Government, insurance companies, and pharmaceutical companies saw an increase in
      perceived "major responsibility" for cost reduction. Respondents vastly preferred
      that patient care under the perioperative surgical home be multidisciplinary.

PMID- 29189274
TI  - Lung Isolation in the Patient With a Difficult Airway.
AB  - One-lung ventilation is routinely used to facilitate exposure for thoracic
      surgical procedures and can be achieved via several lung isolation techniques.
      The optimal method for lung isolation depends on a number of factors that include
      (1) the indication for lung isolation, (2) anatomic features of the upper and
      lower airway, (3) availability of equipment and devices, and (4) the
      anesthesiologist's proficiency and preferences. Though double-lumen endobronchial
      tubes (DLTs) are most commonly utilized to achieve lung isolation, the use of
      endobronchial blockers offer advantages in patients with challenging airway
      anatomy. Anesthesiologists should be familiar with existing alternatives to the
      DLT for lung isolation and alternative techniques for DLT placement in the
      patient with a difficult airway. Newer technologies such as videolaryngoscopy
      with or without adjunctive fiberoptic bronchoscopy may facilitate intubation and
      lung isolation in difficult airway management.

PMID- 29189275
TI  - Ultrasound-Assisted Versus Fluoroscopic-Guided Lumbar Sympathetic Ganglion Block:
      A Prospective and Randomized Study.
AB  - BACKGROUND: Fluoroscopy (FL)-guided lumbar sympathetic ganglion block (LSGB) is
      widely performed to diagnose and manage various diseases associated with
      sympathetically maintained pain. Recently, numerous ultrasound (US)-assisted
      procedures in pain medicine have been attempted, showing an advantage of low
      radiation exposure. This randomized, prospective trial compared the procedural
      outcomes and complications between FL-guided and US-assisted LSGBs. METHODS:
      Fifty LSGBs were randomly divided into 2 groups: FL-guided (FL group) or US
      assisted (US group) LSGB group. Both groups received FL-guided or US-assisted
      LSGB with 10 mL of 0.25% levobupivacaine. The primary end point was the total
      procedure time. Secondary outcomes were success rate, imaging time, onset time
      (based on temperature rise), dosage of radiation exposure, other procedure
      related outcomes, and complications. RESULTS: Total procedure time and success
      rate were not statistically different between the 2 groups, whereas imaging time
      of the US group was longer than that of the FL group (P = .012). The onset time
      was faster in the US group (P = .019), and bone touching during the procedure was
      less frequent in the US group (P = .001). Moreover, radiation exposure was
      significantly lower in the US group than in the FL group (P < .001). No serious
      complications were reported in all patients. CONCLUSIONS: US-assisted LSGB
      appears to be a feasible method with the added benefit of lower radiation
      exposure. In our study, we did not find an advantage of US-assisted LSGB over FL
      guided LSGB in terms of performance time.

PMID- 29189276
TI  - Perioperative Noninvasive Blood Pressure Monitoring.
AB  - The most commonly monitored variable for perioperative hemodynamic management is
      blood pressure. Several indirect noninvasive blood pressure monitoring techniques
      have been developed over the last century, including intermittent techniques such
      as auscultation (Riva-Rocci and Korotkoff) and oscillometry (Marey) and
      continuous techniques. With the introduction of automated noninvasive blood
      pressure devices in the 1970s, the oscillometric technique quickly became and
      remains the standard for automated, intermittent blood pressure measurement. It
      tends to estimate more extreme high and low blood pressures closer to normal than
      what invasive measurements indicate. The accuracy of the oscillometric maximum
      amplitude algorithm for estimating mean arterial pressure is affected by multiple
      factors, including the cuff size and shape, the shape of the arterial compliance
      curve and arterial pressure pulse, and pulse pressure itself. Additionally, the
      technique typically assumes a consistent arterial compliance and arterial
      pressure pulse, thus changes in arterial compliance and arrhythmias that lead to
      variation in the pressure pulse can affect accuracy. Volume clamping, based on
      the Penaz principle, and arterial tonometry provide continuous tracking of the
      arterial pressure pulse. The ubiquitous use of blood pressure monitoring is in
      contrast with the lack of evidence for optimal perioperative blood pressure
      targets.

PMID- 29189278
TI  - Reducing Maternal Mortality in Papua New Guinea: Contextualizing Access to Safe
      Surgery and Anesthesia.
AB  - Papua New Guinea has one of the world's highest maternal mortality rates with
      approximately 215 women dying per 100,000 live births. The sustainable
      development goals outline key priority areas for achieving a reduction in
      maternal mortality including a focus on universal health coverage with safe
      surgery and anesthesia for all pregnant women. This narrative review addresses
      the issue of reducing maternal mortality in Papua New Guinea by contextualizing
      the need for safe obstetric surgery and anesthesia within a structure of enabling
      environments at key times in a woman's life. The 3 pillars of enabling
      environments are as follows: a stable humanitarian government; a safe, secure,
      and clean environment; and a strong health system. Key times, and their
      associated specific issues, in a woman's life include prepregnancy, antenatal,
      birth and the postpartum period, childhood, adolescence and young womanhood, and
      the postchildbearing years.

PMID- 29189279
TI  - Alkalinized Lidocaine Preloaded Endotracheal Tube Cuffs Reduce Emergence Cough
      After Brief Surgery: A Prospective Randomized Trial.
AB  - BACKGROUND: Alkalinized lidocaine in the endotracheal tube (ETT) cuff decreases
      the incidence of cough and throat pain on emergence after surgery lasting more
      than 2 hours. However, alkalinized lidocaine needs 60-120 minutes to cross the
      ETT cuff membrane; therefore, its usefulness in shorter duration surgery is
      unknown. This prospective double-blind randomized controlled trial tested the
      hypothesis that alkalinized lidocaine would reduce the incidence of emergence
      cough after surgeries lasting <120 minutes. METHODS: After local ethics board
      approval, American Society of Anesthesiologists I-III patients consented to be
      randomized into 1 of 2 groups receiving either alkalinized lidocaine (group AL)
      or saline (group S) to inflate the ETT cuff. Cuffs were prefilled >90 minutes
      before intubation with either 2 mL of 2% lidocaine and 8 mL of 8.4% bicarbonate
      (group AL) or 10 mL of normal saline (group S). Cuffs were emptied immediately
      before intubation. After intubation, either 2 mL of 2% lidocaine (AL) or 2 mL of
      saline (S) were injected into the cuff. Additional 8.4% bicarbonate (AL) or
      saline (S) was injected into the cuff until there was no air leak. Anesthesia was
      maintained using desflurane, rocuronium, and either fentanyl or sufentanil to
      maintain vital signs within 20% of baseline values. Opioids administered in
      prophylaxis of extubation cough were proscribed. A standardized "no touch"
      emergence technique was used. A blinded assessor noted any cough above 0.2
      minimum alveolar concentration (MAC) of expired desflurane. At 0.2 MAC, once
      every 30 seconds, the patient was instructed to open his eyes and extubation
      occurred once a directed response was noted. RESULTS: A total of 213 patients
      were randomized and 100 patients in each group completed the experimental
      protocol. The incidence of extubation cough in group AL was 12%, significantly
      lower (1-sided P = .045) than the 22% incidence in group S. The 1-tailed risk
      ratio for cough in group AL was 0.55 (0-0.94, P = .045). Total amount of opioids
      administered (P = .194), ETT cuff preloading times (P = .259), and extubation
      times (P = .331) were not significantly different between groups. The average
      duration of surgery was 59 +/- 28 minutes in group AL and 52 +/- 29 minutes in
      group S (P = .057). CONCLUSIONS: Alkalinized lidocaine in the ETT cuff
      significantly decreased general anesthesia emergence cough after surgeries with
      an average duration of slightly <1 hour.

PMID- 29189280
TI  - The Science of Local Anesthesia: Basic Research, Clinical Application, and Future
      Directions.
AB  - Local anesthetics have been used clinically for more than a century, but new
      insights into their mechanisms of action and their interaction with biological
      systems continue to surprise researchers and clinicians alike. Next to their
      classic action on voltage-gated sodium channels, local anesthetics interact with
      calcium, potassium, and hyperpolarization-gated ion channels, ligand-gated
      channels, and G protein-coupled receptors. They activate numerous downstream
      pathways in neurons, and affect the structure and function of many types of
      membranes. Local anesthetics must traverse several tissue barriers to reach their
      site of action on neuronal membranes. In particular, the perineurium is a major
      rate-limiting step. Allergy to local anesthetics is rare, while the variation in
      individual patient's response to local anesthetics is probably larger than
      previously assumed. Several adjuncts are available to prolong sensory block, but
      these typically also prolong motor block. The 2 main research avenues being
      followed to improve action of local anesthetics are to prolong duration of block,
      by slow-release formulations and on-demand release, and to develop compounds and
      combinations that elicit a nociception-selective blockade.

PMID- 29189281
TI  - Improvement of the Elevated Tryptase Criterion to Discriminate IgE- From Non-IgE
      Mediated Allergic Reactions.
AB  - BACKGROUND: Differentiating between immunoglobulin E (IgE)-dependent and IgE
      independent hypersensitivity reactions may improve the etiologic orientation and
      clinical management of patients with allergic reactions in the anesthesia
      setting. Serum tryptase levels may be useful to discriminate the immune mechanism
      of allergic reactions, but the diagnostic accuracy and optimal cutpoint remain
      unclear.We aimed to compare the diagnostic accuracy of tryptase during reaction
      (TDR) alone and the TDR/basal tryptase (TDR/BT) ratio for discriminating IgE-
      from non-IgE-mediated allergic reactions, and to estimate the best cut point for
      these indicators. METHODS: We included 111 patients (45% men; aged 3-99 years)
      who had experienced an allergic reaction, even though the allergic reaction could
      be nonanaphylactic. Allergy tests were performed to classify the reaction as an
      IgE- or non-IgE-mediated one. The area under the curve (AUC) of the receiver
      operating characteristic analysis was performed to estimate the discriminative
      ability of TDR and TDR/BT ratio. RESULTS: An IgE-mediated reaction was diagnosed
      in 49.5% of patients, of whom 56% met anaphylaxis criteria. The median
      (quartiles) TDR for the IgE-mediated reactions was 8.0 (4.9-19.6) and 5.1 (3.5
      8.1) for the non-IgE-mediated (P = .022). The median (quartiles) TDR/BT ratio was
      2.7 (1.7-4.5) in IgE-mediated and 1.1 (1.0-1.6) in non-IgE-mediated reactions (P
      < .001). The TDR/BT ratio showed the greatest ability to discriminate IgE- from
      non-IgE-mediated reactions compared to TDR (AUC TDR/BT = 0.79 [95% confidence
      interval (CI), 1.1-2.2] and AUC TDR = 0.66 [95% CI, 1.1-2.2]; P = .003). The
      optimal cut point for TDR/BT (maximization of the sum of the sensitivity and
      specificity) was 1.66 (95% CI, 1.1-2.2). CONCLUSIONS: The TDR/BT ratio showed a
      significantly better discriminative ability than TDR to discriminate IgE- from
      non-IgE-mediated allergic reactions. An optimal TDR/BT ratio threshold of
      approximately 1.66 may be useful in clinical practice to classify allergic
      reactions as IgE- or non-IgE-mediated.

PMID- 29189282
TI  - Anesthesia Medication Handling Needs a New Vision.

PMID- 29189283
TI  - Effects of Increasing Airway Pressures on the Pressure of the Endotracheal Tube
      Cuff During Pelvic Laparoscopic Surgery.
AB  - BACKGROUND: Tracheal tube cuff pressures exceeding the perfusion pressures of the
      tracheal mucosa have been associated with complications such as sore throat,
      tracheal mucosa ulcers, tracheal rupture, and subglottic stenosis. Despite
      appropriate inflation, many factors can increase the tracheal cuff pressure
      during mechanical ventilation. This prospective observational cohort study was
      designed to test the hypothesis that during a clinical model of decreasing
      respiratory compliance, the pressure within the endotracheal tube cuff will rise
      in direct relationship to increases in the airway pressures. METHODS: Twenty
      eight adult obese patients (BMI >=30 kg/m) scheduled for elective laparoscopic
      gynecologic procedures were enrolled. All patients received general anesthesia
      utilizing endotracheal tubes with low-pressure high-volume cuffs. After baseline
      adjustment of the cuff pressure to 25 cm H2O, the airway pressures and
      endotracheal cuff pressures were continuously measured using pressure transducers
      connected to the anesthesia circuit and cuff pilot, respectively. Data on cuff
      and airway pressures, mechanical ventilation parameters, intraabdominal
      pressures, and degree of surgical table inclination were collected throughout the
      anesthetic procedure. General linear regression models with fixed and random
      effects were fit to assess the effect of increases in airway pressures on cuff
      pressure, after adjusting for covariates and the clustered structure of the data.
      RESULTS: The mean (standard deviation) age and body mass index were 42.2 (8.8)
      years and 37.7 (5.1) kg/m, respectively. After tracheal intubation, the cuffs
      were overinflated (ie, intracuff pressures >30 cm H2O) in 89% of patients. The
      cuff pressures significantly changed after concomitant variations in the airway
      pressures from a mean (standard error) value of 29.6 (1.30) cm H2O before
      peritoneal insufflations, to 35.6 (0.68) cm H2O after peritoneal insufflation,
      and to 27.8 (0.79) cm H2O after peritoneal deflation (P < .0001). The multilevel
      mixed regression models revealed that after controlling for clustering of the
      data (at the patient and study phase levels) and covariates, increased peak
      airway pressures were significantly associated with increased pressures within
      the endotracheal cuff (coefficient [95% confidence interval], 0.25 [0.14-0.36]; P
      < .0001). Other variables associated with increasing endotracheal cuff pressure
      included degree of surgical table inclination (0.08 [0.04-0.12]; P = .0003) and
      I:E ratio of 1:1 (4.47 [2.10-6.83]; P = .0002). CONCLUSIONS: This clinical model
      of decreased respiratory compliance in mechanically ventilated patients reveals
      that the pressure within the endotracheal cuff significantly changes in direct
      relation to changes in the airway pressures. This finding may have clinical
      relevance in patients requiring prolonged use of high airway pressures.

PMID- 29189287
TI  - Pharmacological considerations in the elderly.
AB  - PURPOSE OF REVIEW: This review discusses the pharmacology of contemporary
      anesthetic medications in geriatric patients, neurophysiological changes with
      aging, current recommendations for dosing anesthetic drugs. It also addresses
      current practice patterns and ongoing studies, which are likely to affect future
      anesthetic drug management in the elderly. RECENT FINDINGS: Potency of anesthetic
      drugs is increased in the elderly. In addition to changes at the receptor level,
      neurophysiological changes in functional connectivity with aging contributes to
      increased sensitivity of anesthetic drugs. However, the extent of reduction is
      underappreciated by the practitioners and dose adjustment is not uniformly
      applied in practice. Large database studies demonstrate association of short-term
      intraoperative hypotension and CNS depression, to poor perioperative outcomes.
      These perturbations are probably of greater consequence in frail, elderly
      patients with reduced reserves. SUMMARY: Anesthetic dosing should be more closely
      age-adjusted to prevent anesthetic-induced hypotension and increased depth of
      anesthesia in the elderly. Pharmacologic studies are required in the elderly
      population (>80 years).

PMID- 29189288
TI  - Clinicopathologic and Molecular Characteristics of Mesonephric Adenocarcinoma
      Arising From the Uterine Body.
AB  - Mesonephric adenocarcinoma (MNAC) is a rare tumor of the female genital tract
      mainly occurring in the uterine cervix. To date, only a few cases of MNAC arising
      from of the uterine body (UB-MNAC) have been reported. The clinicopathologic and
      molecular characteristics of UB-MNAC remain unknown. In this study, we
      investigated the clinical, histopathologic, immunohistochemical, and genetic
      features of UB-MNAC. In total, 11 cases were included. Six patients developed
      metastatic disease, most commonly in lungs (5/6). Histopathologically, UB-MNAC
      was characterized by an admixture of tubular, glandular, papillary, retiform,
      glomeruloid, sex cord-like, and comedonecrosis-like architectural patterns. Three
      adverse pathologic characteristics, including advanced International Federation
      of Gynecology and Obstetrics stage, high mitotic activity, and presence of
      lymphovascular the invasion, were independent factors predicting the development
      of metastasis. All cases were positive for GATA-binding protein 3 and paired box
      2 expression and showed wild-type p53, patchy p16, and preserved PTEN expression,
      as indicated by immunohistochemistry. Next-generation sequencing using 12 samples
      (11 primary tumors and 1 metastatic tumor) revealed 42 single nucleotide
      variations in 16 genes, mostly in KRAS (10/12) and ARID1A (9/12). Copy number
      variation was found in 16 genomic regions, and consisted of 57 gains and 10
      losses, with 1q gain (11/12) being the most prevalent. In conclusion, UB-MNAC
      displays an aggressive biological behavior, with a tendency to metastasize to the
      lungs. Adverse pathologic characteristics reflect the aggressive nature of UB
      MNAC. Distinct molecular features of UB-MNAC include frequent somatic mutations
      of KRAS and ARID1A and gain of 1q.This is an open-access article distributed
      under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives
      License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work
      provided it is properly cited. The work cannot be changed in any way or used
      commercially without permission from the journal.
      http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 29189289
TI  - Meibomian Glands and Ocular Surface Changes After Closure of Meibomian Gland
      Orifices in Rabbits.
AB  - PURPOSE: To investigate changes in the corneal surface, tear film, and meibomian
      glands after meibomian gland orifice closure. METHODS: Seventy-two eyes of 36
      rabbits were used. In the study group (n = 36), the meibomian gland orifices of
      both upper and lower eyelids in the right eyes were electrosurgically coagulated.
      The 36 untreated left eyes were used as controls. Corneal wetting properties were
      measured 1, 3, 7, and 14 days after coagulation. The eyelid sections were stained
      with anti-cytokeratin (CK)1, CK5, and CK6 antibody 8 weeks after coagulation. The
      area of the secretory acini around one meibomian gland duct was measured, and
      meibography of rabbits was performed 8 weeks after meibomian gland orifice
      closure. RESULTS: Three days after coagulation, the corneal wetting property was
      decreased compared with controls. The meibomian gland ducts gradually dilated in
      the study group over time. The epithelium of the central ducts in both groups was
      stained with CK5 and CK6, but not CK1. Although the mean area of the secretory
      acini in the study group (0.10 +/- 0.04 mm) was significantly smaller than that
      of the control group (0.18 +/- 0.04; P = 0.004), meibography showed normal
      morphology in both study and control groups. CONCLUSIONS: Meibomian gland orifice
      closure reduced corneal wetting property and induced meibomian gland duct
      dilation accompanied by shrinkage of secretory acini. Meibography could not
      detect early changes in the meibomian gland after closure of the orifice.
      Therefore, when the orifice is obstructed, more active treatments are needed
      before structural changes occur.

PMID- 29189291
TI  - Effect of Thoracic Epidural Ropivacaine versus Bupivacaine on Lower Urinary Tract
      Function: A Randomized Clinical Trial.
AB  - BACKGROUND: Thoracic epidural analgesia with bupivacaine resulted in clinically
      relevant postvoid residuals due to detrusor underactivity. This study aimed to
      compare the risk of bladder dysfunction with ropivacaine versus bupivacaine using
      postvoid residuals and maximum flow rates. Our hypothesis was that ropivacaine
      would result in lower postvoid residuals, because ropivacaine has been shown to
      have less effect on motor blockade. METHODS: In this single-center, parallel
      group, randomized, double-blind superiority trial, 42 patients undergoing open
      renal surgery were equally allocated to receive epidural bupivacaine 0.125% or
      ropivacaine 0.2%, and 36 were finally included. Inclusion criterion was normal
      bladder function. Patients underwent urodynamic investigations preoperatively and
      during thoracic epidural analgesia. Primary outcome was the difference in
      postvoid residual preoperatively and during thoracic epidural analgesia
      postoperatively. Secondary outcomes were changes in maximum flow rate between and
      within the groups. RESULTS: Median difference in postvoid residual (ml) from
      baseline to postoperatively was 300 (range, 30 to 510; P < 0.001) for bupivacaine
      and 125 (range, -30 to 350; P = 0.011) for ropivacaine, with a significant mean
      difference between groups (-175; 95% CI, -295 to -40; P = 0.012). Median
      difference in maximum flow rate (ml/s) was more pronounced with bupivacaine (-12;
      range, -28 to 3; P < 0.001) than with ropivacaine (-4; range, -16 to 7; P =
      0.025) with a significant mean difference between groups (7; 95% CI, 0 to 12; P =
      0.028). Pain scores were similar. No adverse events occurred. CONCLUSIONS:
      Postvoid residuals were significantly lower using ropivacaine compared to
      bupivacaine for thoracic epidural analgesia reflecting less impairment of
      detrusor function with ropivacaine.

PMID- 29189290
TI  - Period-dependent Associations between Hypotension during and for Four Days after
      Noncardiac Surgery and a Composite of Myocardial Infarction and Death: A Substudy
      of the POISE-2 Trial.
AB  - BACKGROUND: The relative contributions of intraoperative and postoperative
      hypotension to perioperative morbidity remain unclear. We determined the
      association between hypotension and a composite of 30-day myocardial infarction
      and death over three periods: (1) intraoperative, (2) remaining day of surgery,
      and (3) during the initial four postoperative days. METHODS: This was a substudy
      of POISE-2, a 10,010-patient factorial-randomized trial of aspirin and clonidine
      for prevention of myocardial infarction. Clinically important hypotension was
      defined as systolic blood pressure less than 90 mmHg requiring treatment. Minutes
      of hypotension was the exposure variable intraoperatively and for the remaining
      day of surgery, whereas hypotension status was treated as binary variable for
      postoperative days 1 to 4. We estimated the average relative effect of
      hypotension across components of the composite using a distinct effect
      generalized estimating model, adjusting for hypotension during earlier periods.
      RESULTS: Among 9,765 patients, 42% experienced hypotension, 590 (6.0%) had an
      infarction, and 116 (1.2%) died within 30 days of surgery. Intraoperatively, the
      estimated average relative effect across myocardial infarction and mortality was
      1.08 (98.3% CI, 1.03, 1.12; P < 0.001) per 10-min increase in hypotension
      duration. For the remaining day of surgery, the odds ratio was 1.03 (98.3% CI,
      1.01, 1.05; P < 0.001) per 10-min increase in hypotension duration. The average
      relative effect odds ratio was 2.83 (98.3% CI, 1.26, 6.35; P = 0.002) in patients
      with hypotension during the subsequent four days of hospitalization. CONCLUSIONS:
      Clinically important hypotension-a potentially modifiable exposure-was
      significantly associated with a composite of myocardial infarction and death
      during each of three perioperative periods, even after adjustment for previous
      hypotension.

PMID- 29189292
TI  - Closed-Set Speech Discrimination Tests for Assessing Young Children.
AB  - OBJECTIVE: The main objective of this study is to obtain data assessing normative
      scores, test-retest reliability, critical differences, and the effect of age for
      two closed-set consonant-discrimination tests. DESIGN: The two tests are intended
      for use with children aged 2 to 8 years. The tests were evaluated using normal
      hearing children within the appropriate age range. The tests were (1) the closed
      set consonant confusion test (CCT) and (2) the consonant-discrimination subtest
      of the closed-set Chear Auditory Perception Test (CAPT). Both were word
      identification tests using stimuli presented at a low fixed level, chosen to
      avoid ceiling effects while avoiding the use of background noise. Each test was
      administered twice. RESULTS: All children in the age range 3 years 2 months to 8
      years 11 months gave meaningful scores and were able to respond reliably using a
      computer mouse or a touch screen to select one of four response options displayed
      on a screen for each trial. Assessment of test-retest reliability showed strong
      agreement between the two test runs (interclass correlation >= 0.8 for both
      tests). The critical differences were similar to those for other monosyllabic
      speech tests. Tables of these differences for the CCT and CAPT are provided for
      clinical use of the measures. Performance tended to improve with increasing age,
      especially for the CCT. Regression equations relating mean performance to age are
      given. CONCLUSIONS: The CCT is appropriate for children with developmental age in
      the range 2 to 4.5 years and the CAPT is appropriate as a follow-on test from the
      CCT. If a child scores 80% or more on the CCT, they can be further tested using
      the CAPT, which contains more advanced vocabulary and more difficult contrasts.
      This allows the assessment of consonant perception ability and of changes over
      time or after an intervention.

PMID- 29189293
TI  - Mechanisms of rejection in vascular composite allotransplantation.
AB  - PURPOSE OF REVIEW: For patients with devastating injuries in whom standard
      reconstruction is not an option, vascularized composite allotransplantation (VCA)
      has become a viable means of restoring form and function. However, immunological
      rejection continues to be a problem in VCA and has not yet been fully
      characterized. As the field is relatively new, much of the data on rejection and
      immunosuppression have been extrapolated from that of solid organ
      transplantation. In this review, we cover the basic mechanisms of rejection as
      they relate specifically to VCA with analysis of recent literature and future
      directions. RECENT FINDINGS: Recent clinical studies have supported previously
      postulated T-cell-mediated mechanism of acute rejection and have also made
      strides in differentiating rejection from inflammation from other skin conditions
      and with different treatment regimens. Antibody-mediated rejection has been
      described in recent cases as well as treatment of presensitized patients
      receiving VCAs. With more long-term grafts, chronic changes, including
      vasculopathy, are being reported. SUMMARY: Clinically observed types of rejection
      in VCA include mainly cell-mediated, antibody-mediated and chronic rejection.
      Advances in diagnosis and treatment of rejection have been made, but there is
      still much to be learned about VCA-specific rejection.

PMID- 29189294
TI  - Using Choice Architecture to Integrate Substance Use Services with Primary Care:
      Commentary on Donohue et al. (2017).
AB  - : At a time when death and disability linked to problematic substance use have
      reached crisis levels, integration of substance use disorder (SUD) services into
      primary care settings is a clear national priority. Incentive-based interventions
      can catalyze such adoption, but have thus far demonstrated limited
      efficaciousness. Behavioral Economics can inform efforts to incentivize
      healthcare providers to adopt SUD interventions. Choice architecture principles
      dictate pegging rewards to defined quality metrics, improving provider
      information about effective and cost-effective practices, and reducing barriers
      to SUD service provision through technological tools, tackling stigma, and
      addressing real and perceived regulatory burdens and risks. Additional research
      is needed to inform these and other key elements in the choice environment
      designed to facilitate the integration of SUD care into primary care. Success in
      the deployment of the "cascade of care" model in primary care settings during the
      HIV/AIDS epidemic provides room for optimism, but also underscores the urgency of
      rapid scale-up in diagnostic and treatment services for SUD to address the
      burgeoning opioid crisis.

PMID- 29189295
TI  - Effects of Global Payment and Accountable Care on Medication Treatment for
      Alcohol and Opioid Use Disorders.
AB  - OBJECTIVES: The Alternative Quality Contract (AQC) implemented in 2009 by Blue
      Cross Blue Shield of Massachusetts (BCBSMA) is intended to improve quality and
      control costs by putting providers at risk for total medical spending and tying
      payment to performance on specified quality measures. We examined the AQC's early
      effects on use of and spending on medication treatment (MT) for addiction among
      individuals with alcohol use disorders (AUDs) and opioid use disorders (OUDs),
      conditions not subject to any performance measurement in the AQC. METHODS: Using
      data from 2006 to 2011, we use difference-in-difference estimation of the effect
      of the AQC on MT using a comparison group of enrollees in BCBSMA whose providers
      did not participate in the AQC. We compared AQC and non-AQC enrollees with AUDs
      (n = 37,113 person-years) and/or OUDs (n = 12,727 person-years) on any use of MT,
      number of prescriptions filled, and MT spending adjusting for demographic and
      health status characteristics. RESULTS: There was no difference in MT use among
      AQC enrollees with OUD (38.7%) relative to the comparison group (39.1%) (adjusted
      difference = -0.4%, 95% confidence interval -3.8% to 3.0%, P = 0.82). Likewise,
      there was no difference in MT use for AUD between the AQC (6.3%) and comparison
      group (6.5%) (P = 0.64). Similarly, we detected no differences in number of
      prescriptions or spending. CONCLUSIONS: Despite incentives for improved
      integration and quality of care under a global payment contract, the initial 3
      years of the AQC showed no impact on MT use for AUD or OUD among privately
      insured enrollees with behavioral health benefits.

PMID- 29189296
TI  - Long-term outcome after the acute respiratory distress syndrome: different from
      general critical illness?
AB  - PURPOSE OF REVIEW: To review the current research data on long-term outcome and
      health-related quality of life in survivors of the acute respiratory distress
      syndrome (ARDS) and to compare these findings with those from non-ARDS patients
      surviving critical illness. RECENT FINDINGS: Between 6 months and 2 years after
      discharge from ICU, survivors of ARDS present with substantial impairments of the
      levels of body function (muscle strength, walking capacity and/or physical
      activity (physical SF-36 score). In contrast to non-ARDS patients from surgical
      ICUs, a standardized intensified physical therapy during early course of illness
      in ARDS patients could not show an improvement of long-term physical function
      performance. Furthermore, a substantial part of further ARDS patients suffer from
      depression (26-33%), anxiety (38-44%) or posttraumatic stress disorder (22-24%).
      In general, the level of functional autonomy and daily life activities was
      reduced, and in one study, 6 months after ICU-discharge this level was
      significantly lower in ARDS patients compared with non-ARDS patients. In a recent
      study, 44% of ARDS survivors were jobless 1 year after critical illness, whereas
      half of previously employed patients returned to work within 4 months after
      hospital discharge. General health-related quality of life was significantly
      reduced compared with a matched population in all studies. SUMMARY: Surviving
      ARDS is associated with a long-term substantial reduction in health-related
      quality of life and such a reduction does not differ from findings in patients
      surviving other critical illness. In further research, a special attention should
      be paid to prevention measures of the 'post intensive care syndrome' as well as
      to patient important domains, which might better explain the patient's and
      families' demands.

PMID- 29189297
TI  - Are on-scene blood transfusions by a helicopter emergency medical service useful
      and safe? a multicentre case-control study.
AB  - INTRODUCTION: In the prehospital setting, crystalloid fluids are frequently used,
      but only erythrocytes are capable of transporting oxygen to tissues. The aim of
      this study was to establish the efficacy and safety of the prehospital use of
      uncross matched type O rhesus-negative packed red blood cells (URBC) by the Dutch
      physician-staffed helicopter emergency medical service. We hypothesized that
      prehospital URBC transfusions are safe and more effective with respect to
      survival than resuscitations with crystalloids. METHODS: The effects of
      prehospital URBC transfusions were studied by comparing a cohort of patients (>18
      years) who were treated with a combination of URBC and crystalloid fluids with a
      matched control group of patients who received crystalloid fluids alone. RESULTS:
      Among 73 adults who received prehospital URBC transfusions, 50 (68%) patients
      were included. No transfusion reactions were observed. No effect of prehospital
      transfusion on 24-h or 30-day survival was found. Haemoglobin levels at
      presentation to the emergency department were higher in the URBC cohort. The two
      groups had similar cumulative erythrocyte requirements within the first 24 h.
      CONCLUSION: Neither survival benefits nor a decreased incidence of shock on
      admission were observed after prehospital helicopter emergency medical service
      URBC transfusions. There were no prehospital transfusion reactions in this study;
      therefore, URBC transfusions were deemed to be safe. A prospective randomized
      study is warranted to evaluate the effect of early URBC transfusions and
      transfusions with preheated URBC on the survival of patients with severe
      prehospital haemorrhagic shock.

PMID- 29189298
TI  - Laboratory examinations for the vestibular system.
AB  - PURPOSE OF REVIEW: In the last decades, researchers suggested that clinical
      assessment of labyrinthine function in detail became easy thanks to video head
      impulse tests (VHITs), vestibular evoked myogenic potential test (VEMP) and video
      oculography (VOG). It has been argued that they can replace
      electronystagmography, the caloric and rotatory chair tests. This review
      addresses the latest evaluations of these tests and the opportunities they offer,
      but also the limitations in clinical practice. RECENT FINDINGS: The VHIT and
      suppression head impulse test (SHIMP) are under ideal circumstances able to
      accurately identify deficits of the VOR in 3D. However, in a relevant part of the
      patient population, pupil tracking is inaccurate, video-goggles slip and VOR
      quantification is problematic. The dissociation between the VHIT and caloric test
      suggests that these tests are complementary. A new 3D-VOG technique claims to
      quantify eye torsion better than before, opening multiple diagnostic
      possibilities. VEMPs remain difficult to standardize. Variability in normal
      cervical vestibular-evoked myogenic potential amplitude is large. VEMPs become
      smaller or absent with age, raising questions of whether there is a lower normal
      limit at all. Recent research shows that the labyrinth is directly stimulated in
      the MRI offering new opportunities for diagnostics and research. SUMMARY: In
      clinical practice, the VHIT, SHIMP, VEMP and new 3D-VOG techniques improve
      diagnostic power. Unfortunately, technical issues or variability prevent reliable
      quantitative evaluation in a part of the regular patient population. The
      traditional caloric and rotatory chair test can still be considered as valuable
      complementary tests.

PMID- 29189299
TI  - Global orientation in space and the lateralization of brain functions.
AB  - PURPOSE OF REVIEW: The functional role of the vestibular system for multisensory
      orientation and sensorimotor control is reviewed with a special focus on
      hemispherical lateralization and its consequences for neurological disorders of
      higher cortical function. RECENT FINDINGS: The peripheral and central vestibular
      systems are bilaterally organized with ipsilateral and contralateral ascending
      pathways and two multisensory cortical networks in the right and left hemisphere.
      The vestibular cortical system shows a structural and functional lateralization
      with a dominance of the right hemisphere in right-handers and the left hemisphere
      in left-handers. Although the vestibular brainstem pathways are evenly
      distributed at lower pontine level, an increasing lateralization builds up
      because of an asymmetric number of pontine and mesencephalic crossing fibers from
      left to right in right-handers. This vestibular lateralization causes more
      frequent and more severe disorders of higher sensorimotor dysfunction in lesions
      of the right hemisphere such as in hemispatial neglect and the pusher syndrome.
      SUMMARY: There is evidence that multisensory higher vestibular functions
      including large-scale spatial orientation, spatial memory and navigation are
      dominated by the right temporo-parietal cortex. A beneficial result of
      lateralization of brain functions in healthy individuals is that it enables the
      individual to produce a global sensorimotor response even in case of a mismatch
      of the actual right and left sensory inputs. The consequence for neurology,
      however, is that lesions in the dominant hemisphere cause more frequently and
      more severe disorders such as the visuo-spatial hemineglect and the pusher
      syndrome.

PMID- 29189300
TI  - Elevated ALS Biomarker Levels in CSF of a FTD Patient at the Presymptomatic Stage
      of ALS.

PMID- 29189302
TI  - Sex Differences in Neuropsychological Test Performance in Alzheimer's Disease and
      the Influence of the ApoE Genotype.
AB  - BACKGROUND: Only few studies exist reporting sex differences in the Alzheimer
      disease (AD) patients regarding cognitive profile, brain damage, and risk
      factors. The present study investigated the influence of sex in combination with
      the Alzheimer risk allele, epsilon4-allele of apolipoprotein E, on cognitive
      performance. MATERIALS AND METHODS: We examined the effect of sex and ApoE
      genotype on a range of neuropsychological markers from the German version of the
      Consortium to Establish a Registry in Alzheimer's Disease Neuropsychological
      Battery in a monocentric study of 399 AD patients. RESULTS: Male patients had
      significantly more years of school and occupational education compared with
      women. Male AD patients outperformed female patients in tasks of object naming,
      constructional praxis, and constructional praxis recall. There was no
      statistically significant interaction effect between sex and epsilon4-allele of
      apolipoprotein E for any of the examined variables. CONCLUSIONS: The superiority
      of healthy men compared with women in tasks of object naming, constructional
      praxis, and visual memory seems to remain stable when people develop AD,
      indicating larger cognitive reserves in men. In contrast, findings that
      cognitively healthy women outperform men in tests of verbal memory and verbal
      fluency are not stable in AD. Further studies are needed to gain insight in the
      reasons for sex differences.

PMID- 29189301
TI  - Assessing Fitness to Drive in Patients With Different Types of Dementia.
AB  - Dementia is a risk factor for unsafe driving. Therefore, an assessment strategy
      has recently been developed for the prediction of fitness to drive in patients
      with the Alzheimer disease (AD). The aim of this study was to investigate whether
      this strategy is also predictive of fitness to drive in patients with non-AD
      dementia, that is, vascular dementia, frontotemporal dementia, and dementia with
      Lewy bodies. Predictors were derived from 3 types of assessment: clinical
      interviews, neuropsychological tests, and driving simulator rides. The criterion
      was the pass-fail outcome of an official on-road driving assessment. About half
      of the patients with non-AD dementia (n=34) failed the on-road driving
      assessment. Neuropsychological assessment [area under the curve (AUC)=0.786] was
      significantly predictive of fitness to drive in patients with non-AD dementia,
      however, clinical interviews (AUC=0.559) and driving simulator rides (AUC=0.404)
      were not. The fitness-to-drive assessment strategy with the 3 types of assessment
      combined (AUC=0.635) was not found to significantly predict fitness to drive in
      non-AD dementia. Different types of dementia require different measures and
      assessment strategies.

PMID- 29189303
TI  - Biomarkers of Cognitive Impairment: Brain Cortical Thickness, Volumetrics, and
      Cerebrospinal Fluid.

PMID- 29189304
TI  - Interventional Pain Procedures in Physical Medicine and Rehabilitation
      Residencies.
AB  - Exposure to interventional pain procedures is now a required component of
      training in physical medicine and rehabilitation residencies as mandated by the
      Accreditation Council for Graduate Medical Education. Data regarding resident
      exposure and competency in these procedures remain limited. Objectives were to
      determine the volume and type of exposure physical medicine and rehabilitation
      residents have to interventional pain procedures and to obtain faculty-perceived
      opinions regarding competency of incoming fellows as it pertains to
      interventional pain management. Online surveys were sent to program directors of
      physical medicine and rehabilitation residencies and fellowship directors of
      interventional spine, sports medicine, and pain medicine fellowships. Surveys
      inquired about educational methods, the volume of procedures in which residents
      actively participate, and faculty-perceived competency of trainees performing
      procedures. Thirty-nine residency programs and 27 fellowships responded to the
      surveys. Of the 39 residencies that responded, there was great variation in the
      exposure residents receive. Most programs reported that residents have moderate
      exposure to common procedures such as ultrasound-guided knee injections and
      lumbar epidural injections. In addition, while most residency program directors
      report graduates to be "fairly prepared" (33%) to "well prepared" (20.5%) with
      regard to spine procedures, most fellowship directors (63%) describe incoming
      fellows to be at the "beginner" level.

PMID- 29189305
TI  - Rehabilitation Outcomes in Spinal Abscess Patients With and Without a History of
      Intravenous Substance Abuse.
AB  - OBJECTIVE: The aim of the study was to compare functional outcomes of acute
      inpatient rehabilitation for spinal epidural abscess patients with and without
      history of intravenous substance abuse. DESIGN: This is a retrospective case
      series study in freestanding rehabilitation hospital. METHODS: Charts of 28
      spinal epidural abscess patients admitted from January 2012 to September 2015: 13
      with intravenous substance abuse and 15 without intravenous substance abuse were
      reviewed. Both groups received standard-of-care rehabilitation. Statistical
      analyses of Functional Independence Measure scores were conducted using
      individual 2 (substance use) * 2 (rehabilitation status) repeated measures
      analysis of variance. Functional outcomes were defined by total Functional
      Independence Measure scores as well as motor and cognitive subsets. Length of
      stay and morphine equivalents were also compared. RESULTS: There were no
      significant differences between the two groups. There was a significant main
      effect of treatment on total Functional Independence Measure scores (P < 0.001),
      Functional Independence Measure motor scores (P < 0.001), and Functional
      Independence Measure cognitive scores (P < 0.01) from admission to discharge.
      Subsequent Student's t tests revealed that the scores of both groups
      significantly improved on all Functional Independence Measure components. There
      were no group differences on length of stay and morphine equivalents at
      discharge. CONCLUSIONS: Acute inpatient rehabilitation can effectively improve
      functional outcomes in spinal epidural abscess patients with or without
      intravenous substance abuse, even though these two patient groups can vary in
      clinical factors.

PMID- 29189307
TI  - Reply to 'Lumbar Transforaminal Epidural Steroid Injection in Patients With
      Chronic Unilateral Radicular Pain'.

PMID- 29189306
TI  - Does a Rehabilitation Program of Aerobic and Progressive Resisted Exercises
      Influence HIV-Induced Distal Neuropathic Pain?
AB  - OBJECTIVE: Distal symmetrical polyneuropathy is a common neurological sequela
      after HIV, which leads to neuropathic pain and functional limitations.
      Rehabilitation programs with exercises are used to augment pharmacological
      therapy to relieve pain but appropriate and effective exercises are unknown. This
      study explored the safety and effect of moderate-intensity aerobic exercises and
      progressive resisted exercises for HIV-induced distal symmetrical polyneuropathy
      neuropathic pain. DESIGN: A randomized pretest, posttest of 12 wks of aerobic
      exercise or progressive resisted exercise compared with a control. Outcome
      measures were assessed using the subjective periphery neuropathy, brief
      peripheral neuropathy screening, and numeric pain rating scale. Pain was assessed
      at baseline, 6 and 12 wks. Data between groups were compared using Kruskal
      Wallis, Mann-Whitney U test, and within-groups Friedman and Wilcoxon signed rank
      tests. RESULTS: There were 136 participants (mean [SD] age = 36.79 [8.23] yrs)
      and the exercise groups completed the protocols without any adverse effects. Pain
      scores within and between aerobic exercise and progressive resisted exercise
      groups showed significant improvement (P < 0.05) from baseline to 6 and 12 wks
      compared with the control (P > 0.05). CONCLUSIONS: This study supports a
      rehabilitation program of moderate-intensity aerobic exercise and progressive
      resisted exercise being safe and effective for reducing neuropathic pain and is
      beneficial with analgesics for HIV-induced distal symmetrical polyneuropathy.

PMID- 29189308
TI  - Lactotripeptides Supplementations Alleviate the Decrease in Maximal Isometric
      Force After High-Intensity Eccentric Exercise: A Randomized, Placebo-Controlled,
      Double-Blind Clinical Trial.
AB  - OBJECTIVE: The aim of the study was to investigate whether lactotripeptides
      supplementations alleviate the decrease in the maximal isometric force, an
      indirect marker of muscle damage, after eccentric exercise (ECC). DESIGN: Twenty
      two young men performed 50 ECC of the elbow flexors using an isokinetic
      dynamometer. The subjects were randomly assigned to either the placebo or
      lactotripeptides group and were each given a 4.5 mg/d placebo or lactotripeptides
      thrice on the exercise day and the day after. Maximal isometric force and
      brachial arterial diameter were assessed before and 2 days after the ECC.
      RESULTS: The interaction of time and group on maximal isometric force was
      significant (P < 0.05); maximal isometric force was significantly decreased in
      both groups after ECC (P < 0.005). The interaction of brachial arterial diameter
      was significant (P < 0.05); brachial arterial diameter was significantly
      increased in only the lactotripeptides group (P < 0.005). In addition, the change
      in maximal isometric force was significantly related to the change in brachial
      arterial diameter after adjusting for body weight and change in range of motion
      (P < 0.05). CONCLUSIONS: The present results suggest that lactotripeptides
      supplementation alleviates the decrease in the maximal isometric force via an
      increase in brachial arterial diameter after ECC.

PMID- 29189309
TI  - Lumbar Transforaminal Epidural Steroid Injection in Patients With Chronic
      Unilateral Radicular Pain.

PMID- 29189310
TI  - Muscle Damage Due to Fusidic Acid-Statin Interaction: Review of 75 Cases From the
      French Pharmacovigilance Database and Literature Reports.
AB  - BACKGROUND/AREA OF UNCERTAINTY: Statins, which reduce cardiovascular risk in both
      primary and secondary prevention, are one of the most widely prescribed
      therapeutic classes in the world. Usually well-tolerated, statin-associated
      muscle symptoms are a well-known adverse effect. Fusidic acid (FA) is a
      bacteriostatic antibiotic of interest in the treatment of methicillin-resistant
      Staphylococcus aureus infections. Cases of rhabdomyolysis, sometimes fatal, have
      been reported after coprescription of FA and a statin. DATA SOURCES/AREA OF
      UNCERTAINTY: We studied 75 cases of muscle damage related to interaction between
      FA and a statin reported in the French national pharmacovigilance database (43
      cases) and from a literature review (32 cases). RESULTS: Cases were mostly men
      (72.5%), often overweight (mean body mass index: 29.4). The most commonly
      reported statins were atorvastatin (60%), simvastatin (22.7%), and rosuvastatin
      (8.0%). Muscle disorders appeared on average 30 days after initiation of FA.
      Symptoms were muscle weakness (82%), dark urine (71%), and myalgia (61%). Mean
      creatine kinase level at diagnosis was 43,890 UI/mL, and acute renal injury
      occurred more than half of the cases. Outcome was fatal in 22% of cases and 28%
      kept sequelae at the end of the follow-up (54 days). CONCLUSIONS: Muscle damage
      induced by interaction between FA and statin is a potentially life-threatening
      complication, leading to contraindication of this association in France. This is
      to be reminded especially because FA is about to get FDA approval and should soon
      be available in the United States.

PMID- 29189311
TI  - Role of Preemptive Gabapentin on Postoperative Analgesia After Infraumbilical
      Surgeries Under Subarachnoid Block-A Randomized, Placebo-Controlled, Double-Blind
      Study.
AB  - BACKGROUND: Preemptive use of gabapentin might accelerate recovery by reducing
      acute post-inguinal herniorrhaphy pain and opioid requirement being an analgesic.
      STUDY QUESTION: Assessing efficacy of three different doses of oral gabapentin
      premedication for postoperative pain management after inguinal herniorrhaphy
      under spinal anesthesia. STUDY DESIGN: This prospective, randomized, placebo
      controlled study was performed on 120 male patients (ASA I/II) undergoing
      inguinal herniorrhaphy under subarachnoid block. Patients were divided into 4
      groups of 30 patients each to receive placebo (group A) or gabapentin 400 mg (B)
      or 800 mg (C) or 1200 mg (D), administered orally 2 hours before surgery.
      Assessment of postoperative pain was made on the basis of the visual analog score
      (VAS), where 0 cm "no pain" and 10 cm "worst pain imaginable." Patients received
      IV fentanyl 0.5 MUg/kg bolus when VAS >3. MEASURES AND OUTCOMES: VAS score at
      regular intervals, the first analgesic requirement and total opioid consumption
      within 24 hours after surgery along with side/adverse effect (s) of study drug in
      perioperative period. RESULTS: The VAS of the study groups B, C, D were
      significantly lower than placebo group (A) at 0, 1, 2, 4, 8, 12, 16, 20, and 24
      hour intervals after surgery (P < 0.05). The first analgesic need and total
      opioid consumption within 24 hours after surgery of study groups were
      significantly lower than placebo group (P < 0.005) while within study groups
      difference was not significant. Dizziness and somnolence were seen maximally in
      group D patients (P = 0.01). However, pruritus, nausea and vomiting though
      maximally reported among group (A) patients but statistically non-significant.
      CONCLUSION: Preemptive gabapentin is opioid sparing to control postoperative pain
      with anxiolysis and sedation. We found the optimal dose to be 400 mg for
      gabapentin. However, increasing dose from 400 to 1200 mg does not increase its
      efficacy as analgesic but with higher adverse effects.

PMID- 29189312
TI  - Hypoglycemia and Sudden Death During Treatment With Methadone for Opiate
      Detoxification.
AB  - CLINICAL FEATURES: We present a case of a middle-aged man admitted to an
      inpatient detoxification facility for withdrawal of intranasal heroin,
      alprazolam, and ethanol. The patient was placed on methadone and chlordiazepoxide
      tapers. Ondansetron and trazodone were prescribed as needed for symptom control.
      On the third hospital day, the patient was found unresponsive with blood glucose
      of 40 mg/dL. He had no history of glucose dysregulation. The patient was
      pronounced dead shortly thereafter. Methadone overdose was ruled the cause of
      death. THERAPEUTIC CHALLENGES: There have been studies linking methadone with
      glucose dysregulation. Hypoglycemia can induce changes in the electrical system
      in the heart, including lengthening QT interval, lengthening repolarization, and
      causing ST wave changes. In addition, there have been studies linking methadone
      treatment to QT interval prolongation and torsade de pointes. Ondansetron and
      trazodone have both been associated with cardiac conduction abnormalities.
      SOLUTION: We recommend initial blood glucose and cardiac monitoring in patients
      taking methadone 40 mg daily or higher.

PMID- 29189313
TI  - Vedolizumab-Associated Acute Respiratory Distress Syndrome.

PMID- 29189314
TI  - Ivabradine for Treatment of Refractory Tachycardia in a Patient With Hypertrophic
      Cardiomyopathy.

PMID- 29189315
TI  - Intravenous Fluid Therapy in Hospitalized Patients.

PMID- 29189316
TI  - Fingolimod-Associated Intracerebral Lymphoproliferative Disorder.
AB  - Most epidemiological studies indicate that incidence of cancer in multiple
      sclerosis patients is lower than general population. However these studies were
      performed prior to the emergence of disease-modifying therapies (DMTs). The
      incidence of cancer may be influenced by newer generation DMTs which are
      immunomodulatory or immunosuppressant. We describe an atypical case of
      intracerebral plasmacytic lymphoproliferative disorder in a 47 years old patient
      on fingolimod. As worldwide usage of oral and infusion DMTs increases, heightened
      clinical suspicion and early recognition of these serious adverse events remain
      crucial.

PMID- 29189317
TI  - Worsening of Psoriatic Arthritis After Ustekinumab Treatment.

PMID- 29189318
TI  - Standardised noxious stimulation-guided individual adjustment of remifentanil
      target-controlled infusion to prevent haemodynamic responses to laryngoscopy and
      surgical incision: A randomised controlled trial.
AB  - BACKGROUND: The surgical plethysmographic index (SPI) is one of the available
      indexes of the nociception-antinociception (NAN) balance. Individually adjusting
      the NAN balance to prevent somatic responses to noxious stimulation remains a
      challenge. OBJECTIVES: To assess whether guiding remifentanil administration
      according to the SPI response to a calibrated noxious stimulus (NANCAL) can blunt
      the haemodynamic response to tracheal intubation and surgical incision. DESIGN:
      Randomised multicentre study. SETTING: Two Belgian university hospitals from
      January 2014 to April 2015. PATIENTS: After ethic review board approval and
      informed consent, 48 American Society of Anesthesiologists I or II adult patients
      scheduled for surgery under general anaesthesia were enrolled. INTERVENTIONS:
      Patients were randomly assigned to a SPI group, where remifentanil effect-site
      concentration was adjusted according to NANCAL, or a control group, where it was
      fixed at 4 ng ml. Propofol concentration was always adjusted to maintain the
      bispectral index close to 40. NANCAL consisted of a 100 Hz, 60 mA electrical
      tetanic stimulation during 30 s at the wrist before tracheal intubation and
      before surgical incision. MAIN OUTCOME MEASURES: The primary endpoint was the
      efficacy of the NANCAL-guided remifentanil administration to prevent the
      haemodynamic response to tracheal intubation and surgical incision. The secondary
      aim was to compare the ability of SPI, analgesia nociception index, pupil
      diameter and mean arterial pressure response to NANCAL to predict the
      haemodynamic response to tracheal intubation and surgical incision. RESULTS: Our
      SPI response to NANCAL-based correcting scheme for remifentanil administration
      was not superior to a fixed remifentanil concentration at blunting the
      haemodynamic response to tracheal intubation or surgical incision. Among all
      tested NAN balance indices, only mean arterial pressure had significant
      predictive ability with regard to the haemodynamic response to surgical incision.
      CONCLUSION: Further research is needed to define the best NANCAL stimulus and the
      best remifentanil correcting scheme to help individualised tailoring of
      antinociception for each specific subpopulation of surgical patients. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT: 02884310;
      https://clinicaltrials.gov/ct2/show/NCT02884310.

PMID- 29189319
TI  - Ulcerating Tumor of the Scalp: Answer.

PMID- 29189320
TI  - Asymptomatic, Tiny Yellowish Papules on the Back of the Wrist: Answer.

PMID- 29189321
TI  - Verrucous Plaque on the Abdomen: Answer.

PMID- 29189322
TI  - Ulcerating Tumor of the Scalp: Challenge.

PMID- 29189324
TI  - Introduction: Pancreatic Adenocarcinoma: The Emperor of All Cancer Maladies.

PMID- 29189323
TI  - Asymptomatic, Tiny Yellowish Papules on the Back of the Wrist: Challenge.

PMID- 29189325
TI  - Oral Health and the Oral Microbiome in Pancreatic Cancer: An Overview of
      Epidemiological Studies.
AB  - PURPOSE: The aim was to provide a cohesive overview of epidemiological studies of
      periodontal disease, oral microbiome profiles, and pancreatic cancer risk.
      DESIGN: A PubMed search of articles published in English through July 2017 with
      additional review of bibliographies of identified articles. RESULTS: Risk
      estimates for periodontal disease associated with pancreatic cancer consistently
      ranged from 1.5 to 2, aligning with a meta-analysis summary relative risk of
      1.74. Analyses of antibodies to pathogenic and/or commensal oral bacteria in
      prediagnostic blood provided evidence that some oral bacteria and oral microbial
      diversity may be related to pancreatic cancer. CONCLUSIONS: Overall, the data
      present a plausible but complex relationship among pancreatic cancer, the oral
      microbiome, periodontal disease, and other risk factors that might be explained
      by systemic effects on immune and inflammatory processes. Larger comprehensive
      studies that examine serially collected epidemiological/clinical data and blood,
      tissue, and various microbial samples are needed to definitively determine how
      and whether oral health-related factors contribute to pancreatic cancer risk.

PMID- 29189326
TI  - Advances in the Genetics and Biology of Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDA) remains one of the most devastating
      diagnoses in modern medicine. While the clinical management of the disease has
      improved, the complex biologic underpinnings of PDA enable both its aggressive
      nature and slow clinical translational progress. In this review, we provide an
      overview of the key features of PDA genetics and biology, highlighting
      translational challenges and providing a framework for improved diagnostic and
      therapeutic approaches.

PMID- 29189327
TI  - The Pancreatic Cancer Microenvironment.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is composed of a minority of malignant
      cells within a microenvironment of extracellular matrix, fibroblasts, endothelial
      cells, and immune cells. Therapeutic failures of chemotherapy, targeted therapy,
      and immunotherapy have all been attributed to the PDAC microenvironment. In this
      review, we dissect the components of the microenvironment and explain how each
      cell type contributes to form a highly immunosuppressive, hypoxic, and
      desmoplastic cancer. New efforts in single-cell profiling will enable a better
      understanding of the composition of the microenvironment in primary and
      metastatic PDAC, as well as an understanding of how the microenvironment may
      respond to novel therapeutic approaches.

PMID- 29189329
TI  - Diagnosis and Detection of Pancreatic Cancer.
AB  - Computed tomography is the first-line imaging modality for suspected pancreatic
      cancer. Magnetic resonance cholangiopancreatography is a second-line modality for
      suspected pancreatic cancer and is usually reserved for equivocal cases. Both
      computed tomography and MR are highly sensitive in the detection of pancreatic
      cancer, with up to 96% and 93.5% sensitivity, respectively. Computed tomography
      is superior to MR in the assessment of tumor resectability, with accuracy rates
      of up to 86.8% and 78.9%, respectively. Close attention to secondary signs of
      pancreatic cancer, such as pancreatic duct dilatation, abrupt pancreatic duct
      caliber change, and parenchymal atrophy, are critical in the diagnosis of
      pancreatic cancer. Emerging techniques such as radiomics and molecular imaging
      have the potential of identifying malignant precursors and lead to earlier
      disease diagnosis. The results of these promising techniques need to be validated
      in larger clinical studies.

PMID- 29189328
TI  - Understanding Disease Biology and Informing the Management of Pancreas Cancer
      With Preclinical Model Systems.
AB  - Recent advances in cytotoxic therapies for pancreatic ductal adenocarcinoma (PDA)
      are overshadowed by stalled clinical progress of more targeted strategies, the
      vast majority of which have failed in clinical trials. Inability to translate
      preclinical promise into clinical efficacy derives, in part, from imperfect
      disease modeling and mismatches between preclinical and clinical study design and
      execution. Into these gaps fall our patients who enter the clinical trial
      landscape expectantly and bear the brunt of its inadequacies. If improving
      patient survival is paramount, then it must be acknowledged that the failure of a
      phase III trial represents a larger failure of all of the work that preceded it.
      Repeated failures suggest a need to reappraise the current preclinical-to
      clinical apparatus. Exceptional models of PDA are now available to researchers,
      and the first steps toward a new era of success can begin with improved selection
      and application of these systems. We discuss the key features of the major
      preclinical platforms for PDA and propose a paradigm for rigorous interrogation
      of prospective therapies.

PMID- 29189330
TI  - Clinical Management: Resectable Disease.
AB  - Despite the identification of more active systemic therapy combinations for
      pancreatic cancer, cures remain elusive and feasible only in patients with
      localized, operable disease. When examining outcome data from phase III adjuvant
      trials conducted during the past decade, the survival for patients with localized
      disease has improved, likely owing to a combination of factors including more
      active adjuvant therapy and improved surgical and perioperative care. Perhaps the
      greatest recent change in the care of patients with localized pancreatic cancer
      has been the extension of surgery to tumors previously thought to be inoperable
      because of involvement of major blood vessels. These so-called "borderline
      resectable pancreatic cancers" have now been objectively defined, and their
      management is being studied in randomized trials. This has been made feasible by
      the availability of more active systemic therapy combinations that are
      increasingly being used in the neoadjuvant setting. Given the increasing activity
      of systemic regimens, the challenges in delivering such therapy in the
      postoperative setting, and the numerous novel agents in late stages of clinical
      development, it is reasonable to hypothesize that the neoadjuvant setting may
      eventually become the standard of care for patients with resectable disease.

PMID- 29189331
TI  - Ablative Radiotherapy Doses for Locally Advanced: Pancreatic Cancer (LAPC).
AB  - Standard palliative doses of radiation for locally advanced unresectable
      pancreatic cancer have had minimal to no impact on survival. Randomized trials
      evaluating these palliative doses have not shown a significant survival benefit
      with the use of radiation as consolidation after chemotherapy. Results from
      nonrandomized studies of 3- to 5-fraction low-dose stereotactic radiation (SBRT)
      have likewise had a minimal impact, but with less toxicity and a shorter
      treatment time. Doses of SBRT have been reduced to half the level that is
      necessary (biological equivalent dose, BED of 53 Gy) to achieve tumor ablation in
      the treatment of other solid tumors (100 Gy BED) to protect the gastrointestinal
      (GI) tract. The survival benefit of these palliative options is modest. In
      contrast, ablative doses of radiation (100 Gy BED) can be delivered using the
      same SBRT technique in 15 to 25 fractions. In addition to precision tumor
      targeting and solutions for respiratory motion as with SBRT, the delivery of
      ablative doses takes advantage of heterogeneous dosing, increased fractionation,
      which allows higher doses to be given, as well as adaptive planning to address
      day-to-day GI tract motion in selected cases. These higher doses have resulted in
      encouraging long-term survival results in multiple studies. In this review, we
      discuss the critical concepts and components of techniques that can be used to
      deliver ablative radiotherapy doses for patients with pancreatic tumors:
      fractionation, intentional dose heterogeneity, respiratory gating, image
      guidance, and adaptive planning.

PMID- 29189332
TI  - Clinical Management: Metastatic Disease.
AB  - Most patients with pancreatic cancer either present with or eventually develop
      metastatic disease during the course of their illness. For such individuals,
      systemic therapy, namely, cytotoxic therapy, represents the mainstay of treatment
      and is administered with noncurative intent. Of the various chemotherapy options
      now available for treating metastatic pancreatic cancer, 2 combination regimens,
      FOLFIRINOX (infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin)
      and the doublet of gemcitabine and albumin-bound paclitaxel, have emerged as
      frontline standards of care, based on phase III studies demonstrating a
      significant survival benefit compared with single-agent gemcitabine. More
      patients are also now able to be sequenced through 2 or more lines of treatment,
      with newer regimens such as nanoliposomal irinotecan plus infusional 5
      fluorouracil and leucovorin receiving US Food and Drug Administration approval
      specifically for use in this second-line setting. Selection of therapies remains
      primarily guided by clinical considerations, particularly performance status, as
      well as age, comorbid medical conditions, and organ and bone marrow function. In
      contrast, molecular predictors of efficacy and toxicity have not yet been
      validated in this disease context. Areas of novel therapeutic development include
      targeting the stromal microenvironment, exploring combinations of
      immunotherapeutic agents, and identifying molecular subsets of metastatic
      pancreatic cancer that may uniquely susceptible to specific strategies, such as
      hampering DNA damage repair.

PMID- 29189333
TI  - Symptom Management and Palliative Care in Pancreatic Cancer.
AB  - Evidence documents the benefits of palliative care to ameliorate the symptoms of
      pancreatic cancer as well as those from its treatment. Professional organizations
      now recommend palliative care for all patients with pancreatic cancer early in
      the course of illness and concurrently with active treatment. Scrupulous symptom
      management as well as sensitive communication and advance care planning allow
      oncologists to provide "primary palliative care" and to care well for patients
      with pancreatic cancer throughout the course of their illness.

PMID- 29189334
TI  - Considerations in the Care of Athletes With Attention Deficit Hyperactivity
      Disorder.
AB  - OBJECTIVES: Uncover literature pertaining to: (1) attention deficit hyperactivity
      disorder (ADHD) and how it impacts athletes; (2) ADHD medication effects; (3)
      regulations regarding ADHD medications; (4) approaches to conditions similar to,
      and occurring with, ADHD; and (5) use of stimulants. DATA SOURCES: MEDLINE,
      Embase, PsycINFO, Cochrane Database of Systematic Reviews, Ovid interface. MAIN
      RESULTS: ADHD can have many effects on athletes and sports participation.
      Exercise has positive benefits on ADHD behaviors and players' attitudes. Athletes
      with ADHD can have worsened ADHD symptoms after concussions. Attention deficit
      hyperactivity disorder is a modifier of return to play; baseline ADHD symptoms
      should be used to guide management. Management should include medications,
      behavioral/psychosocial therapy, and academic accommodations. Behavioral therapy
      combined with medication is superior to behavioral treatment alone. Sustained
      exercise as ADHD treatment should be considered mainstay in management. Sports
      can increase thermogenic effects of stimulants, heat injury, and cardiac
      arrhythmias. Increased aggressiveness, improved pain tolerance, and decreased
      sense of fatigue are some attributes of stimulants that are presumed to impart
      some advantage to athletes, but evidence is uncertain. Attention deficit
      hyperactivity disorder medications may lead to myocardial infarctions,
      cerebrovascular accidents, paranoid psychoses, seizures, insomnia, tremors,
      anxiety, hypertension, and death. CONCLUSIONS: Athletes' performance and quality
      of life can be negatively affected by ADHD. Risks exist for those who take ADHD
      medications. More research is needed on the implications ADHD may have in
      specific sports, and on possible advantages of medication use. Potential
      deleterious effects of these medications should be addressed.

PMID- 29189335
TI  - Outcomes of Anterior Cruciate Ligament Reconstruction in Obese and Overweight
      Patients: A Systematic Review.
AB  - OBJECTIVE: To evaluate the mechanism of injury, outcomes, and complications of
      anterior cruciate ligament (ACL) reconstruction in overweight and obese patients.
      DATA SOURCES: MEDLINE, EMBASE, and OVID electronic libraries were systematically
      searched from inception to December, 2017 for any eligible articles using a
      combination of the phrases "anterior cruciate ligament," "ACL," "overweight,"
      "obese," and "BMI." RESULTS: Studies that evaluated patients with primary ACL
      reconstruction, classified patients as overweight or obese, and reported a
      minimum of 1-year follow-up data were included. Eight cohorts from 9 studies
      fulfilled the inclusion criteria. There were no significant differences for
      mechanism of injury, Lysholm scores, Knee injury and Osteoarthritis Outcome
      Scores values, or return to sports with a body mass index (BMI) above or below 25
      kg/m. A significant difference was described in International Knee Documentation
      Committee (IKDC) scores when comparing obese patients (BMI >30 kg/m) to patients
      with BMI <25 kg/m (P <0.01). In patients with BMI >25 kg/m, the risk for
      arthritis was significantly higher but the risk for revision surgery or
      contralateral ACL tear was lower (P <0.05). There was no significant difference
      in complication rates (P = 0.77). CONCLUSION: Patient-reported outcome measures
      were similar for patients with BMI above and below 25 kg/m, but there is evidence
      that obese patients have lower IKDC scores. There is a consistent association
      between overweight status and developing arthritis among patients having an ACL
      reconstruction. Overweight and obese patients have a lower risk of revision ACL
      reconstruction and contralateral ACL tear. There is insufficient data to make any
      conclusions regarding mechanism of injury or complications. More research is
      needed to better understand what is the appropriate counsel and treatment for
      overweight or obese patients with ACL tears. PROSPERO REGISTRATION NUMBER:
      CRD42017055594.

PMID- 29189336
TI  - History of High Motion Sickness Susceptibility Predicts Vestibular Dysfunction
      Following Sport/Recreation-Related Concussion.
AB  - OBJECTIVE: To compare vestibular dysfunction at 1 to 10 and 11 to 20 days
      following sport/recreation-related concussion (SRC) in athletes with and without
      history of motion sickness susceptibility. Secondary aims of this study were to
      investigate differences in neurocognitive performance and affective symptoms in
      these groups. DESIGN: Cross-sectional. SETTING: Concussion Specialty Clinic.
      PARTICIPANTS: One hundred twenty-four adolescents and adults (82 males, 42
      females) aged 14 to 26 (16.36 +/- 2.10) years, diagnosed with SRC in the past 10
      (4.56 +/- 2.54) days; 47 participants composed the sample for quartile analyses.
      INDEPENDENT VARIABLE: Motion sickness susceptibility questionnaire short form
      score. MAIN OUTCOME MEASURES: Computerized neurocognitive test scores,
      vestibular/oculomotor screening scores (VOMS), and symptom factor scores from a
      standardized concussion symptom inventory. RESULTS: There was no association
      between history of motion sickness susceptibility and VOMS scores (above or below
      clinical cutoff) at 1 to 10 days after injury, although at 11 to 20 days after
      injury there was an association between high motion sickness susceptibility and
      symptoms above clinical cutoff on 5 of the 6 VOMS items (P values 0.01-0.04). The
      high motion sickness group had more affective symptoms on the symptom inventory
      than the no motion sickness group (P = 0.002) at 1 to 10 days after injury.
      Groups did not differ on computerized neurocognitive testing (P = 0.11).
      CONCLUSION: Athletes with a preexisting history of motion sensitivity may exhibit
      more prolonged vestibular dysfunction following SRC, and may experience more
      affective symptoms early in recovery.

PMID- 29189337
TI  - Postexercise Hypotension as a Predictor for Long-Term Training-Induced Blood
      Pressure Reduction: A Large-Scale Randomized Controlled Trial.
AB  - OBJECTIVE: To investigate the correlation between acute exercise effects and
      chronic training effects on blood pressure (BP). DESIGN: Randomized, controlled
      training study focusing on the optimization of preventive effects of physical
      training. SETTING: The study was performed in a university department.
      PARTICIPANTS: One hundred twenty-seven healthy, untrained subjects. INTERVENTION:
      Subjects were divided into 4 groups: interval endurance training (IET) (n = 26, 4
      * 4 min at 95% maximal heart rate), continuous endurance training (CET) (n = 23,
      45 minutes at 60% heart rate reserve), strength endurance training (SET) (n = 40,
      8 machine-based exercises, each 2 x 15 repetitions at the 20 repetition maximum),
      and control (CON) (n = 38). In the 3 training groups, subjects trained 3 times a
      week for 6 months, the CON group was asked to retain their sedentary lifestyle.
      MAIN OUTCOME MEASURES: The acute exercise effect on BP was defined as the change
      of BP after an exhaustive stage test, compared with baseline. The chronic
      training effect on BP was determined as the change of resting BP after the 6
      month training period. RESULTS: For CET, a significant correlation between acute
      and chronic effects on systolic (r = 0.66, P = 0.001) and diastolic (r = 0.66, P
      = 0.001) BP was observed. For SET, a significant correlation (r = 0.45, P =
      0.007) was found only for diastolic BP. No significant correlations were found
      for IET. CONCLUSIONS: It can be assumed that postexercise hypotension is an easy
      to-use predictor for the efficacy of CET to reduce BP, and may be a valuable tool
      for physicians to individualize prescribed training schedules for patients to
      reduce cardiovascular risk. TRIAL REGISTRATION: www.clinicaltrials.gov; ID:
      NCT01263522.

PMID- 29189338
TI  - Impact of CrossFit-Related Spinal Injuries.
AB  - INTRODUCTION: Exercise-related injuries (ERIs) are a common cause of nonfatal
      emergency department and hospital visits. CrossFit is a high-intensity workout
      regimen whose popularity has grown rapidly. However, ERIs due to CrossFit
      remained under investigated. METHODS: All patients who presented to the main
      hospital at a major academic center complaining of an injury sustained performing
      CrossFit between June 2010 and June 2016 were identified. Injuries were
      classified by anatomical location (eg, knee, spine). For patients with spinal
      injuries, data were collected including age, sex, body mass index (BMI), CrossFit
      experience level, symptom duration, type of symptoms, type of clinic
      presentation, cause of injury, objective neurological examination findings,
      imaging type, number of clinic visits, and treatments prescribed. RESULTS: Four
      hundred ninety-eight patients with 523 CrossFit-related injuries were identified.
      Spine injuries were the most common injuries identified, accounting for 20.9%.
      Among spine injuries, the most common location of injury was the lumbar spine
      (83.1%). Average symptom duration was 6.4 months +/- 15.1, and radicular
      complaints were the most common symptom (53%). A total of 30 (32%) patients had
      positive findings on neurologic examination. Six patients (6.7%) required
      surgical intervention for treatment after failing an average of 9.66 months of
      conservative treatment. There was no difference in age, sex, BMI, or duration of
      symptoms of patients requiring surgery with those who did not. CONCLUSIONS:
      CrossFit is a popular, high-intensity style workout with the potential to injure
      its participants. Spine injuries were the most common type of injury observed and
      frequently required surgical intervention.

PMID- 29189339
TI  - A Prospective, Randomized, Controlled Trial Comparing Conservative Treatment With
      Trunk Stabilization Exercise to Standard Hip Muscle Exercise for Treating
      Femoroacetabular Impingement: A Pilot Study.
AB  - OBJECTIVE: To assess the efficacy of conservative management of women with
      femoroacetabular impingement (FAI) using trunk stabilization. DESIGN: Randomized
      controlled trial (level of evidence: I). SUBJECTS: Twenty FAI female patients who
      met the inclusion FAI criteria. METHODS: A prospective, randomized, controlled
      study was performed on 20 female patients with symptomatic FAI comprising 2
      groups (10 hips in trunk stabilization exercise group vs 10 hips in control
      group). We evaluated hip range of motion, isometric muscle strength using a
      handheld dynamometer (MU-TasMF-01; Anima, Co), and patient-reported outcome
      measures, including modified Harris hip score, Vail hip score, and international
      hip outcome tool 12 (iHOT12) before and at 4 weeks and 8 weeks after the
      intervention. RESULTS: There was a significant improvement in the range of motion
      of hip flexion in the trunk training group detected as early as 4 weeks after the
      intervention compared with the control group (P < 0.05). Hip abductor strength
      significantly improved in the trunk training group at 4 weeks after the
      intervention, whereas it did not improve in the control group (P < 0.05). Vail
      hip score and iHOT12 were significantly increased at 8 weeks after the
      intervention in the trunk training group compared with the control group (iHOT12:
      78.7 +/- 22.4 vs 53.0 +/- 22.3; P < 0.01, Vail hip score: 81.6 +/- 18.5 vs 61.1
      +/- 11.6; P < 0.05). There was no significant difference in the modified Harris
      hip score between both the groups at 4 and 8 weeks after the intervention.
      CONCLUSIONS: The addition of trunk stabilization exercise to a typical hip
      rehabilitation protocol improves short-term clinical outcomes and may augment
      nonoperative and postoperative rehabilitation.This is an open-access article
      distributed under the terms of the Creative Commons Attribution-Non Commercial
      License 4.0 (CCBY-NC), where it is permissible to download, share, remix,
      transform, and buildup the work provided it is properly cited. The work cannot be
      used commercially without permission from the journal.

PMID- 29189340
TI  - Influence of Postconcussion Sleep Duration on Concussion Recovery in Collegiate
      Athletes.
AB  - OBJECTIVE: To determine whether decreased sleep duration postconcussion
      influences days to asymptomatic and assessment of performance throughout
      recovery. DESIGN: Prospective. SETTING: Institutional Clinical Research
      Laboratory. PATIENTS: Four hundred twenty-three collegiate athletes were
      diagnosed with concussion. INTERVENTIONS: Multidimensional concussion assessment
      battery was conducted at baseline, within 24 to 48 hours, daily [2-4 days
      postinjury (PI); symptoms only], once asymptomatic, and after return-to-play. The
      battery included the following: 22-item symptom checklist, Standardized
      Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and
      computerized neurocognitive test [Immediate Post-Concussion Assessment and
      Cognitive Testing (ImPACT)]. MAIN OUTCOME MEASURES: We subtracted baseline sleep
      duration from 24 to 48 hours postconcussion sleep duration and categorized
      athletes into the following groups: shorter sleep (<=-1 hour), no change (>-1
      hour, <+1 hour), and longer sleep (>=+1 hour). A 1-way analysis of variance
      (ANOVA) was conducted to compare days to asymptomatic and separate mixed-model
      ANOVAs to compare total symptom scores, SAC total scores, BESS total error
      scores, and ImPACT composite scores between sleep categories across time points
      (alpha = 0.05). RESULTS: Sleep groups did not differ in days to asymptomatic. The
      shorter sleep group had greater symptom severity than no sleep change and longer
      sleep groups at 24 to 48 hours (shorter: 39.1 +/- 20.7; no change: 25.1 +/- 18.4,
      P = 0.007; longer: 25.7 +/- 21.8, P = 0.004), and at 2 to 4 days PI (shorter:
      21.8 +/- 21.8; no change: 10.5 +/- 10.8, P = 0.013; longer: 11.9 +/- 14.2, P =
      0.007), but did not differ at other time points (ie, asymptomatic and return-to
      play). Participants with shorter sleep exhibited slower ImPACT reaction times at
      24 to 48 hours (shorter: 0.68 +/- 0.14; no change: 0.61 +/- 0.09, P = 0.016; and
      longer: 0.62 +/- 0.12, P = 0.028) and asymptomatic time points (shorter: 0.62 +/-
      0.11; no change: 0.56 +/- 0.05; P = 0.015). CONCLUSION: Postinjury sleep declines
      may be associated with symptom severity and worsened reaction time during initial
      stages of recovery or may be the result of the concussion itself. Clinicians
      should be aware of alterations in sleep duration and manage appropriately to
      mitigate initial symptom burden postconcussion.

PMID- 29189341
TI  - Normative Data Set of SWAY Balance Mobile Assessment in Pediatric Athletes.
AB  - OBJECTIVE: To examine and describe normative values for an objective, mobile
      measure of postural stability commonly used in concussion assessments, SWAY
      Balance (SWAY Medical, Tulsa, Oklahoma). DESIGN: Retrospective analysis of
      baseline balance assessments in a healthy pediatric population. SETTING: Baseline
      assessments completed by certified athletic trainers at an outpatient concussion
      center or sports medicine offices in Philadelphia, PA and surrounding suburban
      Pennsylvania and New Jersey or during an athletic trainer's baseline assessment
      of collegiate athletes at a National Collegiate Athletic Association (NCAA)
      Division-II University in Fort Lauderdale, FL. PARTICIPANTS: Test results of a
      sample of 466 athletes aged 5 to 18 years were included. INTERVENTIONS: The SWAY
      Balance test was administered using a mobile device on all participants as part
      of a standard preseason, baseline evaluation, following the standard evaluation
      protocol. MAIN OUTCOME MEASURES: Baseline SWAY Balance mobile assessment balance
      and reaction time scores, age and sex effects, were examined. RESULTS: Normative
      scores are described, with results stratified into 4 age groups (5-9, 10-12, 13
      17, and 18 years old). Balance scores, overall and within each individual stance
      score, improved with the age of the participants. Sex effects on balance were
      only seen in single-leg stances, with females outperforming males. Reaction time
      was found to be faster in males and improved with age, peaking at 13 to 17 years
      old and slowing in 18-year-olds. CONCLUSIONS: Normative, age-specific SWAY
      Balance test results provided are of clinical use as references in the concussion
      assessments of pediatric athletes.

PMID- 29189342
TI  - The Diagnostic Accuracy of Ultrasound in Detecting Distal Radius Fractures in a
      Pediatric Population.
AB  - OBJECTIVE: Sports ultrasound (US) is becoming popular in diagnosing
      musculoskeletal injuries. This study, also called the Pediatric Distal Radius
      Ultrasound Study (PeDRUS), compared the diagnostic accuracy of sports US with
      plain radiographs in possible distal radius buckle fractures in pediatric
      population. METHODS: In this prospective observational study, patients (2-15
      years) presenting to an outpatient orthopedic injury clinic with distal forearm
      injuries without deformity were recruited. Bedside ultrasonography was performed
      and interpreted by the investigators as positive or negative for fracture. Plain
      radiographs were then performed and interpreted by the same investigator. The
      radiographs were considered the definitive imaging study for this investigation.
      RESULTS: Fifty-one patients were included with a mean age of 9.9 years. Fractures
      were diagnosed on both US and plain radiographs in 34 patients. Fractures were
      ruled out on both US and plain radiographs in 16 patients. There was only one
      case in which the US was interpreted differently than radiograph. For fractures
      of the distal radius in this population, the sensitivity was 97.1% [95%
      confidence interval (CI) = 89.2-97.1] and the specificity was 100% (95% CI = 82.5
      100). The positive predictive value was 100% (95% CI = 91.8-100), whereas the
      negative predictive value was 94.1% (95% CI = 77.7-94.1). The positive likelihood
      ratio was infinite, suggesting utility in confirming a fracture. The negative
      likelihood ratio was 0.03 (95% CI = 0.03-0.13), suggesting that US has value in
      ruling out a fracture. CONCLUSIONS: Our study suggests that diagnostic sports US
      is sensitive and specific for detecting distal radius fractures in pediatric
      patients with nondeformed forearm injuries, demonstrating that US is an
      acceptable alternative to plain radiographs for evaluating fractures in a
      pediatric population.

PMID- 29189344
TI  - Accuracy of Invasive and Noninvasive Parameters for Diagnosing Ventilatory
      Overassistance During Pressure Support Ventilation.
AB  - OBJECTIVE: Evaluate the accuracy of criteria for diagnosing pressure
      overassistance during pressure support ventilation. DESIGN: Prospective clinical
      study. SETTING: Medical-surgical ICU. PATIENTS: Adults under mechanical
      ventilation for 48 hours or more using pressure support ventilation and without
      any sedative for 6 hours or more. Overassistance was defined as the occurrence of
      work of breathing less than 0.3 J/L or 10% or more of ineffective inspiratory
      effort. Two alternative overassistance definitions were based on the occurrence
      of inspiratory esophageal pressure-time product of less than 50 cm H2O s/min or
      esophageal occlusion pressure of less than 1.5 cm H2O. INTERVENTIONS: The
      pressure support was set to 20 cm H2O and decreased in 3-cm H2O steps down to 2
      cm H2O. MEASUREMENTS AND MAIN RESULTS: The following parameters were evaluated to
      diagnose overassistance: respiratory rate, tidal volume, minute ventilation,
      peripheral arterial oxygen saturation, rapid shallow breathing index, heart rate,
      mean arterial pressure, change in esophageal pressure during inspiration, and
      esophageal and airway occlusion pressure. In all definitions, the respiratory
      rate had the greatest accuracy for diagnosing overassistance (receiver operating
      characteristic area = 0.92; 0.91 and 0.76 for work of breathing, pressure-time
      product and esophageal occlusion pressure in definition, respectively) and always
      with a cutoff of 17 incursions per minute. In all definitions, a respiratory rate
      of less than or equal to 12 confirmed overassistance (100% specificity), whereas
      a respiratory rate of greater than or equal to 30 excluded overassistance (100%
      sensitivity). CONCLUSION: A respiratory rate of 17 breaths/min is the parameter
      with the greatest accuracy for diagnosing overassistance. Respiratory rates of
      less than or equal to 12 or greater than or equal to 30 are useful clinical
      references to confirm or exclude pressure support overassistance.

PMID- 29189343
TI  - Kinetics of Urinary Cell Cycle Arrest Markers for Acute Kidney Injury Following
      Exposure to Potential Renal Insults.
AB  - OBJECTIVES: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like
      growth factor binding protein 7 predict the development of acute kidney injury
      following renal insults of varied aetiology. To aid clinical interpretation, we
      describe the kinetics of biomarker elevations around an exposure. DESIGN: In an
      ancillary analysis of the multicenter SAPPHIRE study, we examined the kinetics of
      the urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor
      binding protein 7] in association with exposure to common renal insults (major
      surgery, IV radiocontrast, vancomycin, nonsteroidal anti-inflammatory drugs, and
      piperacillin/tazobactam). SETTING: Thirty-five sites in North America and Europe
      between September 2010 and June 2012. PATIENTS: Seven hundred twenty-three
      critically ill adult patients admitted to the ICU. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We compared the urinary [tissue metalloproteinase
      2]*[insulin growth factor binding protein 7] kinetics from the day prior to
      exposure up to 5 days after exposure in patients developing acute kidney injury
      stage 2-3, stage 1, or no acute kidney injury by Kidney Disease Improving Global
      Outcome criteria. Among the 723 patients, 679 (94%) had at least one, 70% had
      more than one, and 35% had three or more exposures to a known renal insult. There
      was a significant association between cumulative number of exposures up to study
      day 3 and risk of acute kidney injury (p = 0.02) but no association between the
      specific type of exposure and acute kidney injury (p = 0.22). With the exception
      of radiocontrast, patients who developed acute kidney injury stage 2-3 after one
      of the five exposures, had a clear rise and fall of urinary [tissue inhibitor of
      metalloproteinase-2]*[insulin-like growth factor binding protein 7] from the day
      of exposure to 24-48 hours later. In patients without acute kidney injury, there
      was no significant elevation in urinary [tissue inhibitor of metalloproteinase
      2]*[insulin-like growth factor binding protein 7]. CONCLUSIONS: Exposure to
      potential renal insults is common. In patients developing acute kidney injury
      stage 2-3, the kinetics of urinary [tissue inhibitor of metalloproteinase
      2]*[insulin-like growth factor binding protein 7] matched the exposure except in
      the case of radiocontrast.

PMID- 29189345
TI  - Initial Antifungal Strategy Reduces Mortality in Critically Ill Patients With
      Candidemia: A Propensity Score-Adjusted Analysis of a Multicenter Study.
AB  - OBJECTIVE: The objective of this study was to evaluate the impact of the
      empirical therapy with fluconazole or an echinocandin on 30- and 90-day mortality
      in critically ill patients with candidemia. The outcome of patients in whom the
      empirical echinocandin was deescalated to fluconazole was also assessed. DESIGN:
      Retrospective, observational multicenter study. SETTING: Medical and surgical
      ICUs in nine Spanish hospitals. PATIENTS: Adult patients (>= 18 yr) with an
      episode of Candida bloodstream infection during ICU admission from January 2011
      to April 2016. INTERVENTIONS: Patient characteristics, infection-related
      variables, therapeutic interventions, and metastatic complications were reviewed.
      A propensity score-adjusted multivariable analysis was performed to identify the
      risk factors significantly associated with 30-day and 90-day mortality.
      MEASUREMENTS AND MAIN RESULTS: A total of 294 patients were diagnosed of
      candidemia in the participant ICUs. Sixty patients were excluded (other
      antifungals in the primary therapy or the patient died without empirical
      antifungal therapy). The study group comprised 115 patients who received
      fluconazole (30-day mortality, 37.4%) and 119 patients treated empirically with
      an echinocandin (30-day mortality, 31.9%). The use of an echinocandin in the
      empirical therapy was a protective factor for 30-day (odds ratio, 0.32; 95% CI,
      0.16-0.66; p = 0.002) and 90-day mortality (odds ratio, 0.50; 95% CI, 0.27-0.93;
      p = 0.014) in the propensity score- adjusted multivariable analysis. Deescalation
      of the empirical echinocandin to fluconazole was not associated with a higher
      mortality or the occurrence of long-term complications. CONCLUSIONS: Empirical
      use of an echinocandin in critically ill patients with documented candidemia
      reduces mortality at 30 and 90 days significantly. Deescalation of the empirical
      echinocandin to fluconazole is safe and effective in fluconazole-susceptible
      infections.

PMID- 29189346
TI  - Impact of Quality Bundle Enforcement by a Critical Care Pharmacist on Patient
      Outcome and Costs.
AB  - OBJECTIVES: Surgical and medical ICU patients are at high risk of mortality and
      provide a significant cost to the healthcare system. The aim of this study is to
      describe the effect of pharmacist-led interventions on drug therapy and clinical
      strategies on ICU patient outcome and hospital costs. DESIGN: Before and after
      study in two French ICUs (16 and 10 beds). PATIENTS: ICU patients. INTERVENTION:
      From January 1, 2013, to June 30, 2015, a pharmacist observation period was
      compared with an intervention period in which a critical care pharmacist provided
      recommendations to clinicians regarding sedative drugs and doses, choice of
      mechanical ventilation mode and related settings, antimicrobial de-escalation,
      and central venous and urinary catheters removal. Differences in ICU and hospital
      length of stay, duration of mechanical ventilation, mortality rate, and hospital
      costs per patient were quantified between groups with patients matched for
      severity of illness (Simplified Acute Physiology Score II) at admission.
      MEASUREMENTS AND MAIN RESULTS: From the 1,519 and 1,268 admitted patients during
      the observation and intervention periods, respectively, 1,164 patients were
      evaluable in both groups after matching for Simplified Acute Physiology Score II
      score. The intervention period was associated with mean (95% CI) reductions in
      patient hospital length of stay (3.7 d [5.2-2.3 d]; p < 0.001), ICU length of
      stay (1.4 d [2.3-0.5 d]; p < 0.005), duration of mechanical ventilation (1.2 d
      [2.1-0.3 d]; p < 0.01), and hospital costs per stay (2,560 euros [3,728-1,392
      euros]; p < 0.001). The overall cost savings were 10,840 euros (10,727-10,952
      euros) per month, mostly due to reduced consumption of sedatives and
      antimicrobials. No impact on mortality rate was identified. CONCLUSIONS: Critical
      care pharmacist-led interventions were associated with decreases in ICU and
      hospital length of stays and ICU drug costs.

PMID- 29189347
TI  - The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance,
      Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital
      Cardiac Arrest.
AB  - OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog
      exenatide on blood glucose, lactate clearance, and hemodynamic variables in
      comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN:
      Predefined post hoc analyzes from a double-blind, randomized clinical trial.
      SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of
      adult, comatose patients undergoing targeted temperature management after out-of
      hospital cardiac arrest from a presumed cardiac cause, irrespective of the
      initial cardiac rhythm. INTERVENTIONS: Patients were randomized 1:1 to receive 6
      hours and 15 minutes of infusion of either 17.4 MUg of the glucagon-like peptide
      1 analog exenatide (Byetta; Lilly) or placebo within 4 hours from sustained
      return of spontaneous circulation. The effects of exenatide were examined on the
      following prespecified covariates within the first 6 hours from study drug
      initiation: lactate level, blood glucose level, heart rate, mean arterial
      pressure, and combined dosage of norepinephrine and dopamine. MEASUREMENTS AND
      MAIN RESULTS: The population consisted of 106 patients receiving either exenatide
      or placebo. During the first 6 hours from study drug initiation, the levels of
      blood glucose and lactate decreased 17% (95% CI, 8.9-25%; p = 0.0004) and 21%
      (95% CI, 6.0-33%; p = 0.02) faster in patients receiving exenatide versus
      placebo, respectively. Exenatide increased heart rate by approximately 10 beats
      per minute compared to placebo (p < 0.0001). There was no effect of exenatide on
      other hemodynamic variables. CONCLUSIONS: In comatose out-of-hospital cardiac
      arrest patients, infusion with exenatide lowered blood glucose and resulted in
      increased clearance of lactate as well as increased heart rate. The clinical
      importance of these physiologic effects remains to be investigated.

PMID- 29189349
TI  - Role of epigenetics and DNA-damage in asthma.
AB  - PURPOSE OF REVIEW: Although asthma is a common disease worldwide, its
      pathogenesis remains to be fully elucidated. There is increasing evidence of the
      interaction between epigenetics, DNA-damage, and environmental allergens in the
      development of asthma. In this review, we will focus on the role of epigenetics
      and DNA-damage in asthma. RECENT FINDINGS: There is growing evidence of
      environmental allergens, particularly house dust mite, stimulating oxidative DNA
      damage in airway epithelial cells. The repair of this DNA damage has been
      implicated in the secretion of Th2 cytokines and the induction of allergic
      inflammation. SUMMARY: Studies of the role of epigenetics, DNA-damage, and
      environmental allergens have begun to reveal the their complex interactions and
      their roles in the development of asthma. Further study in these areas may lead
      to novel prevention and treatment approaches.

PMID- 29189348
TI  - Should Transfusion Trigger Thresholds Differ for Critical Care Versus
      Perioperative Patients? A Meta-Analysis of Randomized Trials.
AB  - OBJECTIVE: To address the significant uncertainty as to whether transfusion
      thresholds for critical care versus surgical patients should differ. DESIGN: Meta
      analysis of randomized controlled trials. SETTING: Medline, EMBASE, and Cochrane
      Library searches were performed up to 15 June 2016. PATIENTS: Trials had to
      enroll adult surgical or critically ill patients for inclusion. INTERVENTIONS:
      Studies had to compare a liberal versus restrictive threshold for the transfusion
      of allogeneic packed RBCs. MEASUREMENTS AND MAIN RESULTS: The primary outcome was
      30-day all-cause mortality, sub-grouped by surgical and critical care patients.
      Secondary outcomes included myocardial infarction, stroke, renal failure,
      allogeneic blood exposure, and length of stay. Odds ratios and weighted mean
      differences were calculated using random effects meta-analysis. To assess whether
      subgroups were significantly different, tests for subgroup interaction were used.
      Subgroup analysis by trials enrolling critically ill versus surgical patients was
      performed. Twenty-seven randomized controlled trials (10,797 patients) were
      included. In critical care patients, restrictive transfusion resulted in
      significantly reduced 30-day mortality compared with liberal transfusion (odds
      ratio, 0.82; 95% CI, 0.70-0.97). In surgical patients, a restrictive transfusion
      strategy led to the opposite direction of effect for mortality (odds ratio, 1.31;
      95% CI, 0.94-1.82). The subgroup interaction test was significant (p = 0.04),
      suggesting that the effect of restrictive transfusion on mortality is
      statistically different for critical care (decreased risk) versus surgical
      patients (potentially increased risk or no difference). Regarding secondary
      outcomes, for critically ill patients, a restrictive strategy resulted in reduced
      risk of stroke/transient ischemic attack, packed RBC exposure, transfusion
      reactions, and hospital length of stay. In surgical patients, restrictive
      transfusion resulted in reduced packed RBC exposure. CONCLUSIONS: The safety of
      restrictive transfusion strategies likely differs for critically ill patients
      versus perioperative patients. Further trials investigating transfusion
      strategies in the perioperative setting are necessary.

PMID- 29189350
TI  - Asthma: personalized and precision medicine.
AB  - PURPOSE OF REVIEW: In this review, we herein describe the progress in management
      of severe asthma, evolving from a 'blockbuster approach' to a more personalized
      approach targeted to the utilization of endotype-driven therapies. RECENT
      FINDINGS: Severe asthma characterization in phenotypes and endotypes, by means of
      specific biomarkers, have led to the dichotomization of the concepts of
      'personalized medicine' and 'precision medicine', which are often used as
      synonyms, but actually have conceptual differences in meaning. The recent
      contribute of the omic sciences (i.e. proteomics, transcriptomics, metabolomics,
      genomics, ...) has brought this initially theoretic evolution into a more
      concrete level. SUMMARY: This step-by-step transition would bring to a better
      approach to severe asthmatic patients as the personalization of their therapeutic
      strategy would bring to a better patient selection, a more precise endotype
      driven treatment, and hopefully to better results in terms of reduction of
      exacerbation rates, symptoms, pulmonary function and quality of life.

PMID- 29189351
TI  - Lung ultrasound in diagnosing pneumonia in the emergency department: a systematic
      review and meta-analysis.
AB  - Community-acquired pneumonia (CAP) is one of the most widespread and severe
      infectious diseases worldwide. In the emergency department (ED), there is still a
      need for a rapid and accurate tool that can diagnose CAP. Lung ultrasound (LUS)
      is a recent tool that is increasingly being for this purpose. So far, the LUS has
      been evaluated on a wide range of patients, but not yet on the specific
      population in the ED through a meta-analysis. Our aim was to assess the accuracy
      of the LUS in diagnosing CAP in this setting through a systematic review and a
      meta-analysis. A systematic research of literature was carried out for all
      published studies comparing the diagnostic accuracy of the LUS against chest
      radiography or computerized tomography scan in patients older than 18 years of
      age with clinical criteria for CAP assessed in the ED. We extracted the
      descriptive and quantitative data from eligible studies, and calculated the
      pooled sensitivity, specificity, and diagnostic odds ratio. We defined the
      summary receiver operating characteristic curve. Our initial search strategy
      yielded 10 377 studies, of which 17 (0.2%) were eligible. These studies provided
      a combined sample size of 5108 participants. The general risk of bias of the
      considered studies was quite low, but some concerns were highlighted. The
      diagnostic odds ratio was around 181 (I: 27%). The pooled area under the curve,
      sensitivity, and specificity were, respectively, 97, 92, and 93%. The LUS was
      found to be an accurate tool in diagnosing CAP in adult patients in the ED. More
      methodologically rigorous trials are needed.

PMID- 29189352
TI  - Metagenomics in pediatrics: using a shotgun approach to diagnose infections.
AB  - PURPOSE OF REVIEW: With the advent of novel massively parallel sequencing
      technologies and bioinformatic processing capabilities, clinical applications of
      metagenomic studies are rapidly being integrated into medicine. Through this
      paper, we hope to introduce this powerful new tool to clinicians caring for
      children. RECENT FINDINGS: Very few studies have looked at metagenomic
      applications in children. The ability to perform these types of massive
      sequencing projects was not possible as little as 7 years ago. SUMMARY:
      Metagenomics is defined as the study of all genetic material within a given
      sample. Novel sequencing and analysis approaches allow for unbiased assays to
      identify pathogens missed by targeted sequencing and culture methods. Although
      not widely available yet, metagenomic studies have been used to diagnose
      pediatric infections, identify resistance genes in clinical samples, and
      characterize outbreaks. Although cost and turnaround time have limited its
      application in clinical laboratories to date, novel platforms and increasing
      comfort with these techniques continue to push diagnostic metagenomics into
      clinical pediatric medicine. Much work in this field is yet to be done. That
      being said, we feel that pediatric clinicians will be using metagenomic
      techniques in the care of children with increasing frequency in the near future.

PMID- 29189353
TI  - Pediatric palliative oncology: the state of the science and art of caring for
      children with cancer.
AB  - PURPOSE OF REVIEW: Pediatric palliative oncology (PPO) is an emerging field that
      integrates the principles of palliative care early into the illness trajectory of
      children with cancer. PPO providers work with interdisciplinary clinicians to
      provide optimal medical and psychosocial care to children with cancer and their
      families. Ongoing advances in the field of pediatric oncology, including new
      treatment options for progressive cancers, necessitate the early integration of
      palliative care tenets including holistic care, high-quality communication, and
      assessment and management of refractory symptoms. RECENT FINDINGS: Research in
      this emerging field has expanded dramatically over the past several years. This
      review will focus on advancements within several key areas of the field,
      specifically regarding investigation of the communication needs and preferences
      of patients and families, exploration of educational initiatives and
      interventions to teach PPO principles to clinicians, study of patient-reported
      and parent-reported tools to better assess and manage refractory symptoms, and
      development of novel models to integrate palliative care within pediatric
      oncology. SUMMARY: Research findings in the field of PPO, concurrent with
      advances in the treatment of pediatric cancer, may help improve survival and
      quality of life for children with cancer.

PMID- 29189354
TI  - Probiotics for prevention of Clostridium difficile infection.
AB  - PURPOSE OF REVIEW: Probiotics may prevent Clostridium difficile infection (CDI),
      a leading healthcare-associated infection in the United States. However, prior
      studies were limited by heterogeneity in products and patient populations. Recent
      clinical evidence and new approaches to probiotic development are reviewed.
      RECENT FINDINGS: Probiotic use may reduce incident CDI in high-risk populations
      by as much as 50%, though prior clinical trials have yielded conflicting results.
      Combining probiotics with prebiotics improves growth and engraftment in the host.
      Bacillus clausii and Lactobacillus reuteri secrete compounds that directly
      inhibit C. difficile. Organisms that produce secondary bile acids, such as
      Clostridium scindens, enhance C. difficile colonization resistance. Nontoxigenic
      C. difficile, which provides nutritional niche competition, may prevent CDI.
      Refinements to fecal microbiota transplantation (FMT) blur the line between
      probiotics and FMT. These include a quality-controlled stool product (RBX2660),
      purified Firmicutes spores (SER-109) and sterile fecal filtrate. Bacteriophages
      may treat CDI but have unknown safety and efficacy in humans. SUMMARY: There have
      been a number of advances in probiotics and our understanding of their role in
      prevention of CDI, but a number of important safety and efficacy questions
      remain. An improved understanding of the native microbiota structure and function
      will allow for continued development of rationally designed probiotic therapy to
      provide enhanced protection against CDI.

PMID- 29189355
TI  - Massive Transfusion Protocols: When to Turn On, and Off, the Fire Hose.

PMID- 29189356
TI  - Being Mindful in Managing Pain: Integrative Medicine in Chronic Pain Management.

PMID- 29189357
TI  - Dr Ted Eger Obituary.

PMID- 29189358
TI  - The Search for the Optimal Tidal Volume: Why Do We Use Body Weight?

PMID- 29189359
TI  - When Is "Never Enough" (Data) ... Enough?

PMID- 29189360
TI  - Intraoperative Anemia Monitoring: Another Obstacle to Blood Conservation in the
      Surgical Patient.

PMID- 29189361
TI  - The Aortocaval Compression Conundrum.

PMID- 29189362
TI  - Do No Harm, Except Unto Thyself.

PMID- 29189363
TI  - Do You Do What I Do? Cardiac Anesthesia Surveys From Around the Globe.

PMID- 29189364
TI  - Association of Surgery and Anesthesia With Mental Disorder Diagnoses: What Would
      Sir Austin Bradford Hill Say?

PMID- 29189365
TI  - Using Integrative Medicine in Pain Management: An Evaluation of Current Evidence.
AB  - Complementary medicine therapies are frequently used to treat pain conditions
      such as headaches and neck, back, and joint pain. Chronic pain, described as pain
      lasting longer than 3-6 months, can be a debilitating condition that has a
      significant socioeconomic impact. Pharmacologic approaches are often used for
      alleviating chronic pain, but recently there has been a reluctance to prescribe
      opioids for chronic noncancer pain because of concerns about tolerance,
      dependence, and addiction. As a result, there has been increased interest in
      integrative medicine strategies to help manage pain and to reduce reliance on
      prescription opioids to manage pain. This article offers a brief critical review
      of integrative medical therapies used to treat chronic pain, including
      nutritional supplements, yoga, relaxation, tai chi, massage, spinal manipulation,
      and acupuncture. The goal of this article is to identify those treatments that
      show evidence of efficacy and to identify gaps in the literature where additional
      studies and controlled trials are needed. An electronic search of the databases
      of PubMed, The Cochrane Library, EMBASE, PsycINFO, and Science Citation Index
      Expanded was conducted. Overall, weak positive evidence was found for yoga,
      relaxation, tai chi, massage, and manipulation. Strong evidence for acupuncture
      as a complementary treatment for chronic pain that has been shown to decrease the
      usage of opioids was found. Few studies were found in which integrative medicine
      approaches were used to address opioid misuse and abuse among chronic pain
      patients. Additional controlled trials to address the use of integrative medicine
      approaches in pain management are needed.

PMID- 29189366
TI  - Role of Urine Drug Testing in the Current Opioid Epidemic.
AB  - While the evidence for urine drug testing for patients on chronic opioid therapy
      is weak, the guidelines created by numerous medical societies and state and
      federal regulatory agencies recommend that it be included as one of the tools
      used to monitor patients for compliance with chronic opioid therapy. To get the
      most comprehensive results, clinicians should order both an immunoassay screen
      and confirmatory urine drug test. The immunoassay screen, which can be performed
      as an in-office point-of-care test or as a laboratory-based test, is a cheap and
      convenient study to order. Limitations of an immunoassay screen, however, include
      having a high threshold of detectability and only providing qualitative
      information about a select number of drug classes. Because of these restrictions,
      clinicians should understand that immunoassay screens have high false-positive
      and false-negative rates. Despite these limitations, though, the results can
      assist the clinician with making preliminary treatment decisions. In comparison,
      a confirmatory urine drug test, which can only be performed as a laboratory-based
      test, has a lower threshold of detectability and provides both qualitative and
      quantitative information. A urine drug test's greater degree of specificity
      allows for a relatively low false-negative and false-positive rate in contrast to
      an immunoassay screen. Like any other diagnostic test, an immunoassay screen and
      a confirmatory urine drug test both possess limitations. Clinicians must keep
      this in mind when interpreting an unexpected test result and consult with their
      laboratory when in doubt about the meaning of the test result to avoid making
      erroneous decisions that negatively impact both the patient and clinician.

PMID- 29189367
TI  - Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills.
AB  - BACKGROUND: Opioid analgesics are commonly prescribed on an as-needed (PRN) basis
      for acute painful conditions. Uncertainty of how patients actually take PRN
      opioids, coupled with a desire to completely cover pain, leads to variable and
      overly generous opioid prescribing practices, resulting in a surplus of opioids.
      This opioid surplus becomes a source for diversion and nonmedical opioid use.
      Understanding patterns of actual opioid ingestion after acute painful conditions
      can help clinicians counsel patients on safe opioid use, and allow timely
      recognition and intervention when escalating opioid self-dosing occurs, to
      prevent tolerance and addiction. METHODS: We used a novel oxycodone digital pill
      system (ingestible biosensor within a standard gelatin capsule combined with 5-mg
      oxycodone) that when ingested, is activated by the chloride ion gradient in the
      stomach thereby emitting a radiofrequency signal captured by a wearable reader.
      The reader relays ingestion data to a cloud-based server that displays ingestion
      events to the study team. We deployed the oxycodone digital pill among opioid
      naive individuals discharged from the emergency department with acute fracture
      pain. Participants were trained on digital pill operation and discharged with
      twenty-one 5-mg oxycodone digital pills. They were instructed to take digital
      pills PRN for pain on discharge. We conducted a brief interview 7 days after
      study enrollment, at which point participants returned the digital pill system.
      We identified oxycodone ingestion events in real time by data from the digital
      pill system and performed pill counts at the return visit to validate digital
      pill reporting of medication ingestion. RESULTS: In this study, 26 individuals
      were approached; 16 enrolled with 15 completing the study. Participants ingested
      a median of 6 (3-9.5) oxycodone digital pills over the course of 7 days, with 82%
      of the oxycodone dose ingested in the first 3 days. In individuals who required
      operative repair, 86% (N = 6) continued to ingest opioids at 1 week. There was
      substantial variability in ingestion patterns between individuals. CONCLUSIONS:
      The utilization patterns of individuals with acute fracture pain could be
      captured using a digital pill system and revealed a median opioid ingestion of 45
      mg morphine equivalents for acute pain over 7 days. Seven participants ceased
      using opioids within 4 days after discharge from the emergency department,
      although operative repair was associated with longer use. This digital pill
      system was able to measure changes in and patterns of opioid self-dosing, which
      varied between patients.

PMID- 29189369
TI  - In Response.

PMID- 29189368
TI  - Opioid Prescribing for the Treatment of Acute Pain in Children on Hospital
      Discharge.
AB  - BACKGROUND: The epidemic of nonmedical use of prescription opioids has been
      fueled by the availability of legitimately prescribed unconsumed opioids. The aim
      of this study was to better understand the contribution of prescriptions written
      for pediatric patients to this problem by quantifying how much opioid is
      dispensed and consumed to manage pain after hospital discharge, and whether
      leftover opioid is appropriately disposed of. Our secondary aim was to explore
      the association of patient factors with opioid dispensing, consumption, and
      medication remaining on completion of therapy. METHODS: Using a scripted 10
      minute interview, parents of 343 pediatric inpatients (98% postoperative) treated
      at a university children's hospital were questioned within 48 hours and 10 to 14
      days after discharge to determine amount of opioid prescribed and consumed,
      duration of treatment, and disposition of unconsumed opioid. Multivariable linear
      regression was used to examine predictors of opioid prescribing, consumption, and
      doses remaining. RESULTS: Median number of opioid doses dispensed was 43
      (interquartile range, 30-85 doses), and median duration of therapy was 4 days
      (interquartile range, 1-8 days). Children who underwent orthopedic or Nuss
      surgery consumed 25.42 (95% confidence interval, 19.16-31.68) more doses than
      those who underwent other types of surgery (P < .001), and number of doses
      consumed was positively associated with higher discharge pain scores (P = .032).
      Overall, 58% (95% confidence interval, 54%-63%) of doses dispensed were not
      consumed, and the strongest predictor of number of doses remaining was doses
      dispensed (P < .001). Nineteen percent of families were informed how to dispose
      of leftover opioid, but only 4% (8 of 211) did so. CONCLUSIONS: Pediatric
      providers frequently prescribed more opioid than needed to treat pain. This
      unconsumed opioid may contribute to the epidemic of nonmedical use of
      prescription opioids. Our findings underscore the need for further research to
      develop evidence-based opioid prescribing guidelines for physicians treating
      acute pain in children.

PMID- 29189370
TI  - In Response.

PMID- 29189371
TI  - Ectopic Adrenocorticotropic Hormone-Secreting Pituitary Adenoma Localized by 18F
      Choline PET/CT.
AB  - The criterion standard of treatment of an adrenocorticotropic hormone (ACTH)
      secreting pituitary adenoma is complete surgical excision. However, ectopic
      location of these adenomas is an extremely rare condition, which may affect the
      diagnosis and treatment success. We report a case of a 49-year-old man who was
      referred to our institution with persistent hypercortisolemia after an
      unsuccessful attempt of surgical resection. F-choline PET/CT revealed increased
      radiopharmaceutical uptake in a nodule localized in the left maxillary sinus,
      which was proved at histology to be an ectopic ACTH-secreting pituitary adenoma
      staining positive for ACTH. Imaging with F-FDG PET/CT and Ga-DOTA-NOC PET/CT was
      not diagnostic.

PMID- 29189372
TI  - Multifunctional Assessment of Non-Small Cell Lung Cancer: Perfusion-Metabolic
      Correlation.
AB  - PURPOSE: The aim of this study was to investigate the relationship between whole
      tumor CT perfusion and FDG PET/CT parameters in non-small cell lung cancer
      (NSCLC). METHODS: Twenty-five patients with NSCLC were prospectively included. CT
      perfusion parameters calculated were blood flow (BF), blood volume (BV), mean
      transit time, and peak enhancement intensity. SUVmax, SUVpeak, SUVmean, metabolic
      tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated for PET/CT.
      Tumor diameter and volume were measured, and lesions were divided according to
      maximum axial diameter in more than 3 cm and 3 cm or less. The correlations
      between CT perfusion and PET/CT parameters were assessed in all tumors, as well
      as according to tumor diameter and volume. RESULTS: Lesion diameter and volume
      showed a negative correlation with BF and BV (r = -0.78, -0.78, -0.57, -0.48,
      respectively) and a positive correlation with mean transit time (r = 0.55, 0.65,
      respectively). The negative correlation between BF and lesion diameter and volume
      was confirmed in the subgroup of lesions of more than 3 cm (r = -0.68, -0.68,
      respectively). A positive correlation between SUVmax, SUVpeak, SUVmean, and
      lesion volume was observed (r = 0.50, 0.50, 0.46, respectively) and confirmed in
      lesions 3 cm or less (r = 0.81, 0.79, 0.78, respectively). Metabolic tumor volume
      and TLG showed a positive correlation with lesion diameter and volume in the
      overall population (r = 0.93, 0.87, 0.88, 0.90, respectively) and in lesions of
      more than 3 cm (r = 0.89, 0.84, 0.84, 0.79, respectively). Blood flow and BV
      showed a negative correlation with MTV and TLG (r = -0.77, -0.74, and -0.58, 
      0.48, respectively) in the overall population and with MTV in lesions of more
      than 3 cm (r = -0.69, -0.62, respectively). CONCLUSIONS: Perfusion and metabolic
      parameters seem to depend on tumor size. The bigger the tumor, the lower the BF
      and the BV and, conversely, the higher the SUVpeak, MTV, and TLG. This
      information would be useful in the clinical setting when diagnosing or treating
      NSCLC, especially with novel therapies and/or for radiation treatment modulation.

PMID- 29189373
TI  - Incidental Case of Relapsing Polychondritis Detected by 18F-FDG PET/CT.
AB  - A 78-year-old man had fever, persistent wheezing, and serum C-reactive protein
      elevation. Malignant lymphoma was suspected because of mediastinal lymph nodes
      swelling on CT and soluble interleukin 2 receptor elevation. Symmetric F-FDG
      uptake in the tracheobronchial tree and bilateral auricles was observed on
      PET/CT. He was finally diagnosed as having relapsing polychondritis by auricular
      cartilage biopsy. F-FDG PET/CT may have crucial role in evaluating the extent of
      inflammation and deciding the biopsy site of relapsing polychondritis.

PMID- 29189374
TI  - Metastatic Male Breast Cancer With Increased Uptake on 18F-Fluciclovine PET/CT
      Scan.
AB  - Prostate imaging with F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid
      (FACBC, F-fluciclovine) PET/CT scan (Axumin) was recently approved by the US Food
      and Drug Administration for men with suspected prostate cancer recurrence based
      on elevated blood prostate-specific antigen levels following prior treatment. We
      present a rare case of a 77-year-old man with suspected recurrent prostate cancer
      with an incidental finding of advanced-stage breast cancer showing different
      degrees of F-fluciclovine uptake.

PMID- 29189375
TI  - H Syndrome: A Rare Genodermatosis Imaged With 18F-FDG PET/CT.
AB  - H syndrome (OMIM 612391) is an extremely rare autosomal recessive genodermatosis,
      characterized by extensive skin infiltration. We report a case imaged with F-FDG
      PET/CT.

PMID- 29189376
TI  - Clinical Significance of a Solitary Cold Thyroid Nodule in the Setting of Graves
      Disease.
AB  - I-NaI thyroid uptake and scan in a 46-year-old woman with symptomatic
      hyperthyroidism demonstrated marked, diffusely increased uptake consistent with
      Graves disease, as well as a solitary hypofunctioning ("cold") nodule. Pathologic
      evaluation following total thyroidectomy and selective neck dissection revealed
      invasive multifocal papillary thyroid carcinoma in a background of Graves disease
      and 5 of 36 lymph nodes positive for metastatic disease. This case serves as a
      reminder that when present a cold nodule in the setting of Graves disease
      warrants further evaluation for underlying malignancy.

PMID- 29189377
TI  - Focal Autoimmune Pancreatitis Mimicking Pancreatic Cancer on FDG PET/CT Imaging.
AB  - Autoimmune pancreatitis generally results in diffuse increased FDG activity
      throughout the pancreas on PET/CT images. We present a case of focal autoimmune
      pancreatitis with abnormal FDG activity involving only the pancreatic tail on
      PET/CT in a 61-year-old man who was provisionally diagnosed as having pancreatic
      cancer based on the CT findings. The diagnosis of autoimmune pancreatitis was
      based on pathological examination and elevated serum immunoglobulin G4 level.
      Following the steroid therapy, the patient was gradually recovered.

PMID- 29189378
TI  - Simultaneous Brain and Lung Histiocytic Sarcoma Revealed on 18F-FDG PET/CT.
AB  - A 52-year-old man with intermittent head motor tics, aphasia and right upper
      extremity weakness had an F-FDG avid left front lobe brain lesion, and a left
      upper lobe lung lesion on PET/CT. The brain lesion was surgically resected, and
      was diagnosed pathologically as a histiocytic sarcoma (HS). The lung lesion was
      also a HS via bronchial biopsy. HS is rare and generally involves nodes as shown
      on PET/CT in a few case reports. The current case with simultaneous brain and
      lung HS lesions adds new imaging pattern information of the disease to the
      literature.

PMID- 29189379
TI  - Impact of Surgical Margin Width on Recurrence and Overall Survival Following R0
      Hepatic Resection of Colorectal Metastases: A Systematic Review and Meta
      analysis.
AB  - OBJECTIVE: To examine the impact of surgical margin width on survival following
      R0 hepatic resection for colorectal metastases (CRLM). SUMMARY OF BACKGROUND
      DATA: Although negative resection margin is considered of paramount importance
      for the prognosis of patients with colorectal liver metastases, optimal resection
      margin width remains controversial. METHODS: Eligible studies examining the
      association between margin status after R0 hepatic resection for CRLM and
      survival, including overall survival (OS) and disease-free survival (DFS) were
      sought using the Medline, Cochrane, and EMBASE databases. Random-effects models
      were used for the calculation of pooled relative risks (RRs) with their 95%
      confidence intervals (95% CIs). RESULTS: Thirty-four studies were deemed eligible
      for inclusion representing a cohort of 11,147 hepatic resections. Wider resection
      margin (>1 vs <1 cm) was significantly associated with improved OS at 3 years
      (pooled RR = 0.86, 95% CI: 0.79-0.95), 5 years (pooled RR = 0.91, 95% CI: 0.85
      0.97), and 10 years (pooled RR = 0.94, 95% CI: 0.88-1.00). Similarly, DFS was
      positively associated with >1 cm resection margin at 3, 5, and 10 years.
      Interestingly, >1 mm (vs <1 mm) resection margin was significantly associated
      with improved OS at all-time points. Meta-regression analyses did not reveal any
      significant modifying role of the study features under investigation, such as the
      administration of neoadjuvant/adjuvant therapy. CONCLUSIONS: Importantly, our
      findings suggest that while a >1 mm margin is associated with better prognosis
      than a submillimeter margin, achieving a margin >1 cm may result in even better
      oncologic outcomes and should be considered if possible.

PMID- 29189381
TI  - Commentary on Intraoperative Portal Vein Evaluation and Stenting.

PMID- 29189380
TI  - To Cut is to Cure: The Surgeon's Role in Improving Value.

PMID- 29189382
TI  - John L. Cameron: A Historical Perspective.
AB  - : John Lemuel Cameron is one of the most influential surgeons of modern American
      surgery and has had a profound impact on shaping its current global landscape. He
      served as the president of 14 surgical societies and 4 of his presidential
      addresses focused on the lives of surgeons who he believed had made an
      exceptional contribution to the field of surgery: Harvey William Cushing, William
      Stewart Halsted, John Shaw Billings, and John Miller Turpin Finney. Many
      parallels can be drawn between these surgeons and Dr. Cameron. This paper
      describes Dr. Cameron's career in the context of the 4 legendary surgeons, about
      whom he chose to base his presidential addresses.

PMID- 29189383
TI  - Sinai Abbreviated Geriatric Evaluation: Development and Validation of a Practical
      Test.
AB  - OBJECTIVE: To develop and validate a simple geriatric screening tool that
      performs as well as more complex assessments BACKGROUND:: Many tools that predict
      treatment risk in older adults are impractical for routine clinical use. METHODS:
      We prospectively conducted comprehensive preoperative evaluations on 1025
      patients age >=75 years who presented to Sinai Hospital of Baltimore for major
      elective surgery, then retrospectively reviewed patients' medical records for
      occurrence of postoperative outcomes. Using logistic regression modeling and
      receiver operating characteristic curve analysis we selected the best combination
      of simple tests, labeling this the Sinai Abbreviated Geriatric Evaluation (SAGE).
      The performance of the SAGE was then compared with 3 standard tools in its power
      to predict postoperative outcomes. RESULTS: The SAGE is a statistically
      significant predictor of postoperative outcomes. Each unit decrease in SAGE score
      was significantly associated with a 51% (95% CI 1.30-1.77) increase in odds of a
      complication, a 2-fold increase in odds of postoperative delirium (95% CI 1.65
      2.66), a 27% increase in odds of length of hospital stay >2 days (95% CI 1.10
      1.47), a 54% increase in odds of a hospital readmission within 30 days (95% CI
      1.25-2.88), and a 38% increase in odds of an unanticipated discharge to higher
      level care (95% CI 1.18-1.61). We estimated the receiver operating characteristic
      curve area under the curve (AUC) for the SAGE of 0.69, 0.77, 0.73, 0.66, and 0.78
      for the above outcomes, respectively. The SAGE performed as well in predicting
      postoperative outcomes as Fried's frailty phenotype, Charlson Comorbidity Index,
      and American Society of Anesthesiologists Physical Status Class (ASA).
      CONCLUSION: The SAGE performs as well as other geriatric evaluations that require
      equipment or memorization.

PMID- 29189384
TI  - The Evolution of Surgical Strategies for Pancreatic Neuroendocrine Tumors (Pan
      NENs): Time-trend and Outcome Analysis From 587 Consecutive Resections at a High
      volume Institution.
AB  - OBJECTIVE: The objective of the present analysis is 2-fold: first, to define the
      evolution of time trends on the surgical approach to pancreatic neuroendocrine
      neoplasms (Pan-NENs); second, to perform a complete analysis of the predictors of
      oncologic outcome. BACKGROUND: Reflecting their rarity and heterogeneity, Pan
      NENs represent a clinical dilemma. In particular, there is a scarcity of data
      regarding their long-term follow-up after surgical resection. METHODS: From the
      Institutional Pan-NEN database, 587 resected cases from 1990 to 2015 were
      extracted. The time span was arbitrarily divided into 3 discrete clusters
      enabling a balanced comparison between patient groups. Analyses for predictors of
      recurrence and survival were performed, together with conditional survival
      analyses. RESULTS: Among the 587 resected Pan-NENs, 75% were nonfunctioning
      tumors, and 5% were syndrome-associated tumors. The mean age was 54 years (+/-14
      years), and 51% of the patients were female. The median tumor size was 20 mm
      (range 4 to 140), 62% were G1, 32% were G2, and 4% were G3 tumors. Time trends
      analysis revealed that the number of resected Pan-NENs constantly increased,
      while the size (from 25 to 20 mm) and G1 proportion (from 65% to 49%) decreased
      during the study period. After a mean follow-up of 75 months, recurrence analysis
      revealed that nonfunctioning tumors, tumor grade, N1 status, and vascular
      invasion were all independent predictors of recurrence. Regardless of size, G1
      nonfunctioning tumors with no nodal involvement and vascular invasion had a
      negligible risk of recurrence at 5 years. CONCLUSIONS: Pan-NENs have been
      increasingly diagnosed and resected during the last 3 decades, revealing reliable
      predictors of outcome. Functioning and nodal status, tumor grade, and vascular
      invasion accurately predict survival and recurrence with resulting implications
      for patient follow-up.

PMID- 29189385
TI  - Portal Inflow Modulation by Somatostatin After Major Liver Resection: A Pilot
      Study.
AB  - : Major hepatectomy (MH) can lead to an increasing portal vein pressure (PVP) and
      to lesions of the hepatic parenchyma. Several reports have assessed the
      deleterious effect of a high posthepatectomy PVP on the postoperative course of
      MH. Thus, several surgical modalities of portal inflow modulation (PIM) have been
      described. As for pharmacological modalities, experimental studies showed a
      potential efficiency of Somatostatin to reduce PVP and flow. To our knowledge, no
      previous clinical reports of PIM using somatostatin are available. Herein, we
      report the results of PIM using somatostatin in 10 patients who underwent MH with
      post-hepatectomy PVP > 20 mmHg. Our results suggest Somatostatin could be
      considered as an efficient reversible PIM when PVP decrease is above 2.5 mmHg.

PMID- 29189386
TI  - Postoperative Voiding Dysfunction: The Preferred Method for Catheterization.
AB  - OBJECTIVES: Bladder drainage can be achieved by clean intermittent self
      catheterization (CISC), transurethral indwelling catheterization (TIC), or with a
      suprapubic tube (SPT). The primary objective of this study was to determine
      patient preference for catheter type in the management of potential voiding
      dysfunction after pelvic organ prolapse (POP) surgery. METHODS: Between 2012 and
      2016, patients scheduled for POP surgery were recruited into the study. Before
      surgery, patients were informed of the potential for postoperative voiding
      dysfunction and the catheter choices were discussed. Each patient's choice was
      recorded along with baseline information, surgery performed, and perioperative
      details. After surgery, voiding dysfunction, length of catheter use, scores on a
      catheter satisfaction questionnaire, as well as uroflowmetry and urine culture
      testing were assessed. RESULTS: Of those recruited to the study (N = 150), 6.7%
      chose CISC, 7.3% chose TIC, and 86% chose SPT. Catheter satisfaction score 1 week
      after surgery was significantly better for SPT compared with CISC and TIC (P =
      0.005). In addition, at week 1, 33% of CISC, 25% of TIC, and 13% of SPT had a PVR
      of more than 30% (P = 0.002) on uroflowmetry, and 33% of CISC, 50% of TIC, and
      24% of SPT had a positive urine culture (P = 0.05). CONCLUSIONS: This study has
      shown that patients prefer SPT over CISC and TIC for management of voiding
      dysfunction after POP surgery. Use of SPT showed better satisfaction rates,
      better uroflowmetry results, and lower infection rates 1 week after surgery.
      Patient preference is an important factor in this decision and can help
      facilitate a clinical approach.

PMID- 29189387
TI  - Ex Vivo-expanded Natural Killer Cells Derived From Long-term Cryopreserved Cord
      Blood are Cytotoxic Against Primary Breast Cancer Cells.
AB  - With over 600,000 units of umbilical cord blood (CB) stored on a global scale, it
      is important to elucidate the therapeutic abilities of this cryopreserved
      reservoir. In the advancing field of natural killer (NK) cell cancer
      immunotherapy, CB has proven to be a promising and noninvasive source of
      therapeutic NK cells. Although studies have proven the clinical efficacy of using
      long-term cryopreserved CB in the context of hematopoietic stem cell
      transplantations, little is known about its use for the ex vivo expansion of
      effector immune cells. Therefore, our group sought to derive ex vivo-expanded NK
      cells from long-term cryopreserved CB, using an artificial antigen presenting
      cell-mediated expansion technique. We compared the expansion potential and
      antitumor effector function of CB-derived NK (CB-NK) cells expanded from fresh
      (n=4), short-term cryopreserved (<1-year old, n=5), and long-term cryopreserved
      (1-10-year old, n=5) CB. Here, we demonstrated it is possible to obtain an
      exponential amount of expanded CB-NK cells from long-term cryopreserved CB. Ex
      vivo-expanded CB-NK cells had an increased surface expression of activating
      markers and showed potent antitumor function by producing robust levels of
      proinflammatory cytokines, interferon-gamma, and tumor necrosis factor-alpha.
      Moreover, expanded CB-NK cells (n=3-5) demonstrated cytotoxicity towards primary
      breast cancer cells (n=2) derived from a triple-negative breast cancer and an
      estrogen receptor-positive/progesterone receptor-positive breast cancer patient.
      Long-term cryopreservation had no effect on the expansion potential or effector
      function of expanded CB-NK cells. Therefore, we propose that long-term
      cryopreserved CB remains clinically useful for the ex vivo expansion of
      therapeutic NK cells.

PMID- 29189389
TI  - Editorial: I Pledge.

PMID- 29189388
TI  - CD11c-targeted Delivery of DNA to Dendritic Cells Leads to cGAS- and STING
      dependent Maturation.
AB  - Immunotherapeutic activation of tumor-specific T cells has proven to be an
      interesting approach in anticancer treatment. Particularly, anti-CTLA-4 and anti
      PD-1/PD-L1 treatment looks promising, and conceivably, even better clinical
      results might be obtained if such treatment could be combined with boosting the
      existing tumor-specific T-cell response. One way to achieve this could be by
      increasing the level of maturation of dendritic cells locally and in the draining
      lymph nodes. When exposed to cancer cells, dendritic cells may spontaneously
      mature because of danger-associated molecular patterns derived from the tumor
      cells. Double-stranded DNA play a particularly important role in the activation
      of the dendritic cells, through engagement of intracellular DNA-sensors, and
      signaling through the adaptor protein STING. In the present study, we have
      investigated the maturational response of human monocyte-derived dendritic cells
      (moDC) and human monocytic THP-1 cells to targeted and untargeted DNA. We used an
      anti-CD11c antibody conjugated with double-stranded DNA to analyze the maturation
      status of human moDCs, as well as maturation using a cGAS KO and STING KO THP-1
      cell maturation model. We found that dendritic cells can mature after exposure to
      cytoplasmic double-stranded DNA delivered through CD11c-mediated endocytosis.
      Moreover, we show that THP-1 cells matured using IL-4, GM-CSF, and ionomycin
      upregulate DC-maturation markers after CD11c-targeted delivery of double-stranded
      DNA. This upregulation is completely abrogated in cGAS KO and STING KO cells.

PMID- 29189390
TI  - Quality of Life of Implant-Supported Overdenture and Conventional Complete
      Denture in Restoring the Edentulous Mandible: A Systematic Review.
AB  - OBJECTIVE: The aim of this systematic review was to evaluate the oral health
      related quality of life (OHRQoL) associated with an implant-supported overdenture
      (IOD) compared with a conventional complete denture (CCD) in restoring the
      edentulous mandible. METHODS: A literature search was performed in the MEDLINE
      (through Ovid), PubMed, and Cochrane Library databases for articles published
      between 1990 and July 2016. The search was restricted to articles published in
      English. Two reviewers selected the articles based on the inclusion and exclusion
      criteria. Another 2 reviewers analyzed the data. RESULTS: From 108 articles that
      were obtained, 5 articles met the inclusion criteria. Four studies had a high
      risk of bias, and 1 study had an unclear risk of bias. There was a significant
      difference in Oral Health Impact Profile (OHIP) scores between pre- and post
      treatment within the groups and in posttreatment OHIP scores between IOD and CCD
      groups. CONCLUSION: Regarding the edentulous mandible, patients benefited more
      from the IOD with 2 implants, as determined by OHRQoL scores. Considering the
      differences between each domain of the Oral Health Impact Profile (OHIP)
      questionnaire and the lack of long-term performance, more random control trials
      with sufficient sample sizes need to be designed to investigate long-term
      performance after treatment.

PMID- 29189391
TI  - Blood biomarkers for early diagnosis of oesophageal cancer: a systematic review.
AB  - BACKGROUND: Oesophageal cancer prognosis remains poor owing to the inability to
      detect the disease at an early stage. Nontissue (serum, urinary or salivary)
      biomarkers potentially offer less invasive methods to aid early detection of
      oesophageal cancer. We aimed to systematically review studies assessing the
      relationship between nontissue biomarkers and subsequent development of
      oesophageal cancer. METHODS: Using terms for biomarkers and oesophageal cancer,
      Medline, EMBASE and Web of Science were systematically searched for longitudinal
      studies, published until April 2016, which assessed the association between
      nontissue biomarkers and subsequent oesophageal cancer risk. Random effects meta
      analyses were used to calculate pooled relative risk (RR) and 95% confidence
      intervals (CIs), where possible. RESULTS: A total of 39 studies were included.
      Lower serum pepsinogen I concentrations were associated with an increased risk of
      oesophageal squamous cell carcinoma (n=3 studies, pooled RR=2.20, 95% CI: 1.31
      3.70). However, the association for the pepsinogen I : II ratio was not
      statistically significant (n=3 studies, pooled RR=2.22, 95% CI: 0.77-6.40), with
      a large degree of heterogeneity observed (I=68.0%). Higher serum glucose
      concentrations were associated with a modestly increased risk of total
      oesophageal cancer (n=3 studies, pooled RR=1.27, 95% CI: 1.02-1.57). No
      association was observed for total cholesterol and total oesophageal cancer risk
      (n=3 studies, pooled RR=0.95, 95% CI: 0.58-1.54). Very few studies have assessed
      other biomarkers for meta-analyses. CONCLUSION: Serum pepsinogen I concentrations
      could aid early detection of oesophageal squamous cell carcinoma. More
      prospective studies are needed to determine the use of other nontissue biomarkers
      in the early detection of oesophageal cancer.

PMID- 29189392
TI  - Validation of inflammation-based prognostic models in patients with hepatitis B
      associated hepatocellular carcinoma: a retrospective observational study.
AB  - BACKGROUND AND OBJECTIVE: The objective of this study was to investigate the
      prognostic significance of several inflammation-based models in hepatitis B
      associated hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We
      retrospectively reviewed 470 cases of hepatitis B-associated HCC. Preoperative
      data were collected to calculate the inflammation-based markers, including
      systemic immune-inflammation index (neutrophil*platelets/lymphocyte), platelets
      to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio (NLR). Overall survival
      and recurrence-free survival were estimated by the Kaplan-Meier method and Cox
      analysis. RESULTS: During a median follow-up time of 29 months, 34.0% (160/470)
      of patients died and 36.0% (169/470) experienced recurrence. Compared with
      patients with lower scores of inflammation models, patients in the higher group
      had larger tumor diameter and higher risk of vascular invasion (both P<0.05).
      Multivariate analysis revealed that age, tumor size, platelets-to-lymphocyte
      ratio, NLR, and systemic immune-inflammation index were the independent
      predictors for both overall survival and recurrence-free survival. Furthermore,
      the combination of tumor size and NLR showed a significantly better
      discrimination ability for survival (C-index=0.716, 95% confidence interval:
      0.664-0.768) than both Barcelona Clinic Liver Cancer and Cancer of Liver Italian
      Program. CONCLUSION: The inflammation-based markers, in particular the
      combination of NLR with tumor size, are effective tools for assessing prognosis
      in hepatitis B-associated HCC.

PMID- 29189393
TI  - Acute pancreatitis in the elderly: a cause for increased concern?
AB  - BACKGROUND: Acute pancreatitis (AP) is an aggressive and potentially fatal
      clinical condition. Although all age groups are at risk, the elderly may be a
      group of special concern. We aimed at evaluating clinical outcomes of patients
      with elderly-onset AP. MATERIALS AND METHODS: Using a single-center retrospective
      database, treatment and follow-up records of 550 patients admitted with AP were
      reviewed. Outcomes included mortality, admission to the ICU, need for
      interventional procedures, nutritional support, and length of hospital and ICU
      stay. Elderly-onset AP was defined as an episode of AP occurring in patients
      older than 65 years. RESULTS: A total of 263 patients were classified as having
      elderly-onset AP. There was an association between older age and higher Ranson
      and the bedside index of severity in AP scores, translating into longer lengths
      of hospital stay, higher requirements for ICU admission, interventional
      procedures, organ failure, persistent organ failure, and overall mortality. In
      multivariate analysis, age was an independent predictor of mortality in AP.
      CONCLUSIONS: Age was strongly associated with a more severe course of AP. Early
      recognition and prompt action are essential to improve outcomes in this
      population.

PMID- 29189394
TI  - Ischemic stroke in liver cirrhosis: epidemiology, risk factors, and in-hospital
      outcomes.
AB  - BACKGROUND AND AIMS: Patients with cirrhosis are reportedly more prone to develop
      hemorrhagic stroke, thereby increasing the risk of death. However, the effect of
      ischemic stroke on liver diseases remains unclear. In addition, few studies have
      explored the risk factors for ischemic stroke in patients with liver cirrhosis.
      Our study aimed to explore the epidemiology, risk factors, and in-hospital
      outcomes of ischemic stroke in a large cohort of hospitalized patients with
      cirrhosis. PATIENTS AND METHODS: In this single-center observational study, we
      retrospectively reviewed the medical records of patients with liver cirrhosis
      admitted to our hospital from January 2011 to June 2014. A diagnosis of ischemic
      stroke was further identified. RESULTS: Of the 2444 patients with liver
      cirrhosis, 160 had ischemic stroke, including 128 patients with previous ischemic
      stroke and 32 patients with new-onset ischemic stroke during their
      hospitalizations. Compared with patients with cirrhosis without ischemic stroke,
      those with ischemic stroke were significantly older; had a significantly higher
      proportion of arterial hypertension and a significantly lower proportion of
      hepatitis B virus infection; had significantly higher white blood cell, platelet,
      blood urea nitrogen, and triglyceride levels; and had significantly lower alanine
      aminotransferase and aspartate aminotransferase levels and prothrombin time. The
      in-hospital mortality was significantly higher in patients with ischemic stroke
      than in those without [8.80% (14/160) vs. 3.2% (72/2284), P=0.001]. CONCLUSION:
      Ischemic stroke was often observed in patients with cirrhosis, and it
      significantly increased the in-hospital mortality. The association of
      inflammation, coagulation disorders, and viral hepatitis with development of
      ischemic stroke in liver cirrhosis should be further evaluated in prospective
      cohort studies.

PMID- 29189395
TI  - Augmented Quadruple-Phase Contrast Media Administration and Triphasic Scan
      Protocol Increases Image Quality at Reduced Radiation Dose During Computed
      Tomography Urography.
AB  - PURPOSE: The aim of this article was to investigate the opacification of the
      renal vasculature and the urogenital system during computed tomography urography
      by using a quadruple-phase contrast media in a triphasic scan protocol. MATERIALS
      AND METHODS: A total of 200 patients with possible urinary tract abnormalities
      were equally divided between 2 protocols. Protocol A used the conventional single
      bolus and quadruple-phase scan protocol (pre, arterial, venous, and delayed),
      retrospectively. Protocol B included a quadruple-phase contrast media injection
      with a triphasic scan protocol (pre, arterial and combined venous, and delayed),
      prospectively. Each protocol used 100 mL contrast and saline at a flow rate of
      4.5 mL. Attenuation profiles and contrast-to-noise ratio of the renal arteries,
      veins, and urogenital tract were measured. Effective radiation dose calculation,
      data analysis by independent sample t test, receiver operating characteristic,
      and visual grading characteristic analyses were performed. RESULTS: In arterial
      circulation, only the inferior interlobular arteries in both protocols showed a
      statistical significance (P < 0.05). Venously, the inferior vena cava, proximal
      and distal renal veins demonstrated a significant opacification reduction in
      protocol B than in protocol A (P < 0.001). Protocol B showed a significantly
      higher mean contrast-to-noise ratio than protocol A (protocol B: 22.68 +/- 13.72;
      protocol A: 14.75 +/- 5.76; P < 0.001). Radiation dose was significantly reduced
      in protocol B (7.38 +/- 2.22 mSv) than in protocol A (12.28 +/- 2.72 mSv) (P <
      0.001). Visual grading characteristic (P < 0.027) and receiver operating
      characteristic (P < 0.0001) analyses demonstrated a significant preference for
      protocol B. CONCLUSIONS: In computed tomography urography, augmented quadruple
      phase contrast media and triphasic scan protocol usage increases the image
      quality at a reduced radiation dose.

PMID- 29189396
TI  - Computed Tomography-Based Texture Analysis to Determine Human Papillomavirus
      Status of Oropharyngeal Squamous Cell Carcinoma.
AB  - OBJECTIVE: To determine whether machine learning can accurately classify human
      papillomavirus (HPV) status of oropharyngeal squamous cell carcinoma (OPSCC)
      using computed tomography (CT)-based texture analysis. METHODS: Texture analyses
      were retrospectively applied to regions of interest from OPSCC primary tumors on
      contrast-enhanced neck CT, and machine learning was used to create a model that
      classified HPV status with the highest accuracy. Results were compared against
      the blinded review of 2 neuroradiologists. RESULTS: The HPV-positive (n = 92) and
      -negative (n = 15) cohorts were well matched clinically. Neuroradiologist
      classification accuracies for HPV status (44.9%, 55.1%) were not significantly
      different (P = 0.13), and there was a lack of agreement between the 2
      neuroradiologists (kappa = -0.145). The best machine learning model had an
      accuracy of 75.7%, which was greater than either neuroradiologist (P < 0.001, P =
      0.002). CONCLUSIONS: Useful diagnostic information regarding HPV infection can be
      extracted from the CT appearance of OPSCC beyond what is apparent to the trained
      human eye.

PMID- 29189397
TI  - Patterns of Coronary Calcification and Their Impact on the Diagnostic Accuracy of
      Computed Tomography Coronary Angiography.
AB  - OBJECTIVE: Despite coronary calcifications being a major factor affecting the
      diagnostic accuracy of coronary computed tomography angiography (CTA), there is a
      lack of established criteria for categorizing calcifications. We aimed to
      evaluate patterns of coronary calcification based on quantitative radiodensity
      and size parameters to provide coronary calcium categories and assess their
      impact on the accuracy of coronary CTA. METHODS AND RESULTS: We analyzed length,
      maximum thickness, volume, mean density, and maximum density of coronary calcium
      and divided each of these parameters into tertiles. Subsequently, we summarized
      the tertiles for each individual calcification and divided them into 3 equal
      groups of: mild, moderate, and severe calcification. The accuracy of coronary CTA
      was defined as the difference between the measurements obtained on coronary CTA
      versus the reference of intravascular ultrasound (IVUS). We evaluated 252
      coronary calcifications within 97 arteries of 60 patients. There was an expected
      increase in size and density values for mild versus moderate versus severe
      calcifications, but there was no difference in IVUS measured minimum lumen area
      among the 3 groups. Of note, coronary CTA significantly underestimated IVUS
      minimum lumen area measurement by 1.2 +/- 1.6 mm (14.6 +/- 23.1%, P < 0.001) for
      severe calcifications and by 0.5 +/- 2.0 mm (3.7 +/- 32.1%, P = 0.021) for
      moderate calcifications. Within mild calcifications, the difference was not
      significant. CONCLUSION: Based on their dimensional and radiodensity
      characteristics, our analysis revealed patterns of individual coronary artery
      calcifications that affected the accuracy of coronary CTA measurements; coronary
      CTA inaccuracy was associated with the presence of moderate or severe
      calcifications, but not mild calcifications.

PMID- 29189399
TI  - Performance of Magnetic Resonance Susceptibility-Weighted Imaging for Detection
      of Calcifications in Patients With Hepatic Echinococcosis.
AB  - OBJECTIVE: We evaluated the performance of susceptibility-weighted imaging (SWI)
      for identification of hepatic calcifications in alveolar echinococcosis and
      cystic echinococcosis. METHODS: The SWI images of 58 lesions in 40 patients (age,
      49 +/- 14 y) with alveolar echinococcosis (n = 22) or cystic echinococcosis (n =
      18) were reviewed for calcifications. First, calcifications were suggested by
      visual assessment. Second, ratios of minimum intralesional intensity and mean
      lumbar muscle intensity were recorded. Computed tomography (CT) served as the
      criterion standard. RESULTS: Thirty-seven lesions showed calcifications on CT.
      Susceptibility-weighted imaging provided a sensitivity of 89.2% (95% confidence
      interval [CI], 50.1-75.7) and a specificity of 57.1% (95% CI, 34.4-77.4) for
      calcifications detected by visual assessment. Receiver operating characteristic
      curves demonstrated a sensitivity of 67.6% and a specificity of 85.0% for an
      intensity ratio of 0.61. A specificity of 100% (95% CI, 80.8-100) and a
      sensitivity of 84.5% (95% CI, 67.3-93.2) were achieved by SWI for calcifications
      with a density greater than 184 HU in CT. CONCLUSIONS: Identification of hepatic
      calcifications is possible with SWI. Susceptibility-weighted imaging offers the
      potential to reduce the need for of CT imaging for evaluation of echinococcosis.

PMID- 29189398
TI  - Quantification of the Effect of Shuttling on Computed Tomography Perfusion
      Parameters by Investigation of Aortic Inputs on Different Table Positions From
      Shuttle-Mode Scans of Lung and Liver Tumors.
AB  - OBJECTIVES: The aim of this study was to quantify the effect of shuttling on
      computed tomography perfusion (CTp) parameters derived from shuttle-mode body CT
      images using aortic inputs from different table positions. METHODS: Axial shuttle
      mode CT scans were acquired from 6 patients (10 phases, 2 nonoverlapping table
      positions 1.4 seconds apart) after contrast agent administration. Artifacts
      resulting from the shuttling motion were corrected with nonrigid registration
      before computing CTp maps from 4 aortic levels chosen from the most superior and
      inferior slices of each table position scan. The effect of shuttling on CTp
      parameters was estimated by mean differences in mappings obtained from aortic
      inputs in different table positions. Shuttling effect was also quantified using
      95% limits of agreement of CTp parameter differences within-table and between
      table aortic positions from the interaortic mean CTp values. RESULTS: Blood flow,
      permeability surface, and hepatic arterial fraction differences were
      insignificant (P > 0.05) for both within-table and between-table comparisons. The
      95% limits of agreement for within-table blood volume (BV) value deviations
      obtained from lung tumor regions were less than 4.7% (P = 0.18) compared with
      less than 12.2% (P = 0.003) for between-table BV value deviations. The 95% limits
      of agreement of within-table deviations for liver tumor regions were less than
      1.9% (P = 0.55) for BV and less than 3.2% (P = 0.23) for mean transit time,
      whereas between-table BV and mean transit time deviations were less than 11.7% (P
      < 0.01) and less than 14.6% (P < 0.01), respectively. Values for normal liver
      tissue regions were concordant. CONCLUSIONS: Computed tomography perfusion
      parameters acquired from aortic levels within-table positions generally yielded
      higher agreement than mappings obtained from aortic levels between-table
      positions indicating differences due to shuttling effect.

PMID- 29189401
TI  - Comparing Fourth Generation Statistical Iterative Reconstruction Technique to
      Standard Filtered Back Projection in Pediatric Head Computed Tomography
      Examinations.
AB  - OBJECTIVE: Although advanced statistical iterative reconstruction (IR) techniques
      are valued in pediatric computed tomography (CT) imaging, there is little
      published data on how these techniques affect image quality and radiation dose in
      the pediatric population. This is particularly true in the context of pediatric
      head CT examinations. This study analyzed the differences in image quality and
      several standard metrics of radiation dose on multidetector pediatric head CT
      examinations performed using standard filtered back projection (FBP) with
      reconstructions using iDose, a fourth-generation statistical iterative
      reconstruction technique. MATERIALS AND METHODS: Using a retrospective review of
      282 pediatric head CT examinations, we compared how iDose fared against FBP for
      effects on several standard metrics of radiation dose and qualitative and
      quantitative assessment of image quality. RESULTS: Our assessment revealed that
      examinations obtained using low-dose protocols reconstructed using iDose, when
      compared with standard-dose examinations reconstructed using FBP, resulted in
      significant radiation dose reduction while performing equally or better in
      quantitative image quality parameters. For most qualitative image quality
      parameters, the iDose group demonstrated equal performance to standard filtered
      back technique with a few notable exceptions. In the parameter of image sharpness
      in the 1.5 to 7 year olds, iDose fared better than FBP. However, FBP outperformed
      iDose in the qualitative parameters of decreased image graininess/noise in
      patients older than 13 years, improved image sharpness in patients aged between 7
      and 13 years, and improved visibility of small parts for those aged 7 to 13
      years. CONCLUSIONS: We conclude that iDose is effective at allowing significant
      radiation dose reduction while maintaining or, rarely, even improving
      quantitative image quality compared with FBP in the setting of pediatric head CT
      examinations. However, for certain qualitative image quality parameters in older
      aged children, the use of iDose resulted in a poorer performance compared with
      FBP.

PMID- 29189400
TI  - Assessment of Myometrial Invasion in Premenopausal Grade 1 Endometrial Carcinoma:
      Is Magnetic Resonance Imaging a Reliable Tool in Selecting Patients for Fertility
      Preserving Therapy?
AB  - OBJECTIVES: The aim of this study was to evaluate the diagnostic ability of
      magnetic resonance imaging (MRI) in premenopausal women with G1 endometrial
      carcinoma. METHODS: Twenty-six patients underwent T2W, diffusion weighted, and
      dynamic contrast-enhanced 3-T MRI. The degree of myometrial invasion was
      pathologically classified into no invasion, shallow (3 mm or less), and more. Two
      radiologists assessed myometrial invasion on MRI. Diagnostic accuracy,
      sensitivity, specificity, positive and negative predictive values, AUC, and
      interobserver agreement were analyzed. RESULTS: For assessing myometrial
      invasion, mean accuracy, sensitivity, specificity, positive predictive values,
      negative predictive values, and AUC, respectively, were as follows: 63%, 42%,
      85%, 79%, 47%, and 0.75. Mean interobserver agreement was fair (k = 0.36).
      Shallow invasions were underestimated as no invasion on MRI in all 6 cases.
      CONCLUSIONS: Magnetic resonance imaging produced false-negative result on half of
      patients. The misjudgments tended to happen in patients with shallow invasion.

PMID- 29189402
TI  - Correlation Between Semen Analysis Parameters and Diffusion-Weighted Magnetic
      Resonance Imaging of the Testicles in Patients With Varicocele: A Pilot Study.
AB  - PURPOSE: The aims of this study were to evaluate using testicle apparent
      diffusion coefficient (ADC) values in patients with varicocele and compare them
      with those of healthy individuals, to identify an optimal ADC threshold level to
      predict abnormal semen analysis using diffusion-weighted imaging. MATERIALS AND
      METHODS: Thirty-one patients with the diagnosis of varicocele and 20 healthy
      controls were enrolled in the study. All subjects underwent testicle diffusion
      weighted imaging at b values of 0, 400, and 800 s/mm and semen analysis. Student
      t tests were used to compare continuous variables between 2 groups. Testicle ADC
      values were correlated with semen analysis parameters. The relationship between
      ADC values and impaired semen analysis parameters was evaluated using Pearson
      correlation coefficient analysis. Receiver operating characteristic curves were
      formed. Cut-off values for ADC, sensitivity, and specificity values were
      measured. RESULTS: There was a negative correlation between mean ADC values and
      plexus pampiniformis vein diameter (r = -0.467, P < 0.001) and a positive
      correlation between mean ADC values and sperm count (r = 0.838, P < 0.001) as
      well as sperm morphology (r = 0.548, P < 0.05). Sensitivity values of 94.3% and
      86.6% and specificity values of 87.5% and 43.8% were determined for the best cut
      off ADC values in diagnosing the sperm count and morphology, respectively (area
      under the curve, 0.961 and 0.781). CONCLUSIONS: Decreased testicular ADC values
      in patients with varicocele are significantly correlated with semen parameters.
      This method may be used to determine the degree of testicular parenchymal
      destruction. In addition, testicular ADC cut-off values might be useful in
      dyspermia patients for the management of patients with varicocele.

PMID- 29189403
TI  - How Do Different Indices of Hepatic Enhancement With Gadoxetic Acid Compare in
      Predicting Liver Failure and Other Major Complications After Hepatectomy?
AB  - OBJECTIVE: The objective of this study was to assess the accuracy of gadoxetic
      acid hepatic enhancement indices in predicting posthepatectomy liver failure
      (PHLF) and other major complications (OMCs). METHODS: Sixty-five patients
      underwent prehepatectomy gadoxetic acid-enhanced magnetic resonance imaging.
      Enhancement indices were calculated by obtaining regions of interest on magnetic
      resonance images and segmented volumes of the liver and spleen. Multivariate
      regression analysis was performed to predict PHLF and OMC as a function of the
      indices, and areas under the receiver operator characteristic (AUROC) curves were
      calculated. RESULTS: Areas under the receiver operator characteristic values
      varied from 0.412 to 0.681 and 0.462 to 0.738 in predicting PHLF and OMC,
      respectively. The most accurate indices in predicting PHLF were the region of
      interest-based, fat-normalized relative liver enhancement and liver enhancement
      index (AUROC, 0.681). The most accurate index in predicting OMC was the
      volumetric least-squares regression slope of a pharmacokinetic model (Khep_V,
      AUROC, 0.738). CONCLUSIONS: Indices of gadoxetic acid liver enhancement
      demonstrate variable performance in predicting PHLF and OMC.

PMID- 29189404
TI  - Artifactual Appearance of Thrombosis on Using Metal Artifact Reduction Software
      Reconstruction in Computed Tomographic Angiography.
AB  - The authors attempted to use metal artifact reduction software in 2 computed
      tomographic angiogram studies to decrease beam hardening. Although the beam
      hardening artifacts were reduced in the postprocessed images, there was an
      artifactual appearance of thrombosis in the adjacent arteries in the first case
      and in the inflow cannula of a left ventricular assist device in the second case.
      Comparison of the reconstructed images with the original images is therefore
      essential to avoid a misdiagnosis.

PMID- 29189405
TI  - Intrahepatic Mass-Forming Cholangiocarcinoma: Relationship Between Computed
      Tomography Characteristics and Histological Subtypes.
AB  - OBJECTIVE: The aim of this study was to determine the value of multi-detector row
      computed tomography (MDCT) in differentiating the small-duct (SD) and large-duct
      (LD) types of intrahepatic mass-forming cholangiocarcinomas (IMCCs) and
      predicting patient prognosis. METHODS: The 4-phase MDCT image findings of 82
      patients with surgically confirmed IMCCs (60 SD-type and 22 LD-type IMCCs) were
      compared between 2 types using univariate and multivariate analyses. Overall
      survival rates for 78 patients with available information were compared using the
      Kaplan-Meier method. RESULTS: Arterial hyperenhancement, round or lobulated
      contour, and lack of bile duct encasement were significant MDCT features
      suggesting the SD type, and lymph node enlargement was significantly associated
      with the LD type (all P's < 0.05). The presence of those 3 SD-type-suggestive
      features (MDCT-suggested SD type) demonstrated high specificity (90.9% [20/22])
      in differentiating the SD type. Patients of MDCT-suggested SD type without lymph
      node enlargement (n = 24) demonstrated significantly better overall survival than
      other groups. CONCLUSIONS: Preoperative MDCT features of IMCCs can help
      differentiate the SD and LD types and predict patient prognosis.

PMID- 29189406
TI  - Cleidocranial Dysplasia: A Review of Clinical, Radiological, Genetic Implications
      and a Guidelines Proposal.
AB  - In this review, we aimed to depict the clinical, radiological, and genetic
      features of cleidocranial dysplasia (CCD) and to suggest management guidelines,
      based on our experience of 8 cases, with an emphasis given to dental
      complications.The most common craniofacial features of CCD that stand out are a
      patency of the anterior fontanelle, an inverted pear-shaped calvaria, a
      hypertelorism, a general midface retrusion, and a mandible prognathism,
      associated with an excessive mobility of the shoulders, a short stature, and
      teeth abnormalities such as supernumerary teeth and failure of eruption, in
      particular. RUNX2 is the only gene in which mutation is known to cause CCD, but
      mutations are detected in only 65% of all patients with a clinical diagnosis of
      CCD. Panoramic radiography is a valuable adjunct in confirming the diagnosis of
      CCD.Our experience allowed us to conclude that orthodontically aided eruption
      should always be attempted. However, to stabilize the occlusion and to improve
      facial esthetics, we recommend associated orthognathic surgery. When orthodontic
      treatment is partially efficient, prosthetic treatment options bring satisfactory
      results, in terms of occlusion. Nevertheless, when orthodontic treatment fails,
      we recommend to preserve as many native teeth as possible, and to combine
      orthognathic preprosthetic surgery and implant-supported prosthesis.In any case,
      an individualized treatment protocol, depending on the needs and demand of the
      patient, the age at diagnosis and social and economic circumstances, should be
      put forward.

PMID- 29189407
TI  - Effect of Resistance Training to Muscle Failure vs. Volitional Interruption at
      High- and Low-Intensities on Muscle Mass and Strength.
AB  - Nobrega, SR, Ugrinowitsch, C, Pintanel, L, Barcelos, C, and Libardi, CA. Effect
      of resistance training to muscle failure vs. volitional interruption at high- and
      low-intensities on muscle mass and strength. J Strength Cond Res 32(1): 162-169,
      2018-The purpose of this study was to investigate the effects of resistance
      training (RT) at high- and low-intensities performed to muscle failure or
      volitional interruption on muscle strength, cross-sectional area (CSA), pennation
      angle (PA), and muscle activation. Thirty-two untrained men participated in the
      study. Each leg was allocated in 1 of 4 unilateral RT protocols: RT to failure at
      high and low intensities, and RT to volitional interruption (repetitions
      performed to the point in which participants voluntarily interrupted the
      exercise) at high (HIRT-V) and low (LIRT-V) intensities. Muscle strength (1
      repetition maximum [1RM]), CSA, PA, and muscle activation by amplitude of the
      electromyography (EMG) signal were assessed before (Pre), after 6 (6W), and 12
      (12W) weeks. 1RM increased similarly after 6W (range: 15.8-18.9%, effective size
      [ES]: 0.41-0.58) and 12W (range: 25.6-33.6%, ES: 0.64-0.98) for all protocols.
      All protocols were similarly effective in increasing CSA after 6W (range: 3.0
      4.6%, ES: 0.10-0.24) and 12W (range: 6.1-7.5%, ES: 0.22-0.26). PA increased after
      6W (~3.5) and 12W (~9%; main time effect, p < 0.0001), with no differences
      between protocols. EMG values were significantly higher for the high-intensity
      protocols at all times (main intensity effect, p < 0.0001). In conclusion, both
      HIRT-V and LIRT-V are equally effective in increasing muscle mass, strength, and
      PA when compared with RT performed to muscle failure.

PMID- 29189408
TI  - Monoamine Oxidase Inhibitor Switching Strategies: No Adverse Events Associated
      With Outpatient Cross-taper or Inpatient Rapid Switch.

PMID- 29189409
TI  - Serotonin and Love: Supporting Evidence From a Patient Suffering From Obsessive
      Compulsive Disorder.

PMID- 29189410
TI  - Health and Well-Being Metrics in Business: The Value of Integrated Reporting.
AB  - OBJECTIVE: Health and well-being (HWB) are material to sustainable business
      performance. Yet, corporate reporting largely lacks the intentional inclusion of
      HWB metrics. This brief report presents an argument for inclusion of HWB metrics
      into existing standards for corporate reporting. METHODS AND RESULTS: A Core
      Scorecard and a Comprehensive Scorecard, designed by a team of subject matter
      experts, based on available evidence of effectiveness, and organized around the
      categories of Governance, Management, and Evidence of Success, may be integrated
      into corporate reporting efforts. CONCLUSIONS: Pursuit of corporate integrated
      reporting requires corporate governance and ethical leadership and values that
      ultimately align with environmental, social, and economic performance. Agreement
      on metrics that intentionally include HWB may allow for integrated reporting that
      has the potential to yield significant value for business and society alike.

PMID- 29189411
TI  - Diverse roles of TIM4 in immune activation: implications for alloimmunity.
AB  - PURPOSE OF REVIEW: T-cell immunoglobulin and mucin domain-containing molecule
      (TIM)4 is a costimulatory molecule and phosphatidylserine receptor. Its dominant
      function varies according to the expressing cell and site of activation. In
      recent years, studies have identified its role in diverse disease processes and
      increasingly in alloimmunity. Herein, we will comprehensively review the
      literature on TIM4 and outline its function in shaping the alloimmune response.
      RECENT FINDINGS: TIM4 expression on dendritic cells increases following
      transplantation. Blockade of TIM4 in vivo leads to increased differentiation of
      regulatory T cells and improved allograft survival. TIM4 binds phosphatidylserine
      expressing apoptotic cells. Previously thought of as a tethering molecule, recent
      studies have demonstrated that TIM4 interacts with integrins to mediate uptake of
      apoptotic cells. TIM4 B cells have recently been identified, which produce high
      levels of IFNgamma and promote allograft rejection. Targeting these B cells
      improved allograft survival and promoted the development of TIM1 regulatory B
      cells. SUMMARY: TIM4 is expressed in niche compartments and has many
      immunological effects. However, inhibition of TIM4 has been demonstrated to
      prolong allograft survival, through varied mechanisms. A unifying explanation for
      the role of TIM4 in alloimmunity remains to be found, but this pathway appears to
      hold considerable promise in transplantation.

PMID- 29189412
TI  - Harnessing the lymph node microenvironment.
AB  - PURPOSE OF REVIEW: To evaluate role of the lymph node in immune regulation and
      tolerance in transplantation and recent advances in the delivery of antigen and
      immune modulatory signals to the lymph node. RECENT FINDINGS: Lymph nodes are a
      primary site of immune cell priming, activation, and modulation, and changes
      within the lymph node microenvironment have the potential to induce specific
      regulation, suppression, and potentially tolerance. Antigen enters the lymph node
      either from tissues via lymphatics, from blood via high endothelial venules, or
      directly via injection. Here we review different techniques and materials to
      deliver antigen to the lymph node including microparticles or nanoparticles, ex
      vivo antigen presenting cell manipulation, and use of receptor conjugation for
      specific intralymph node targeting locations. SUMMARY: The promising results
      point to powerful techniques to harness the lymph node microenvironment and
      direct systemic immune regulation. The materials, techniques, and approaches
      suggest that translational and clinical trials in nonhuman primate and patients
      may soon be possible.

PMID- 29189414
TI  - What's new in transplantation tolerance?

PMID- 29189415
TI  - Bone Formation Using Cross-Linked Chitosan Scaffolds in Rat Calvarial Defects.
AB  - PURPOSE: To investigate the osteoconductive effect of a chitosan scaffold in a
      rat skull defect model. Previous publications have demonstrated the
      osteoinductive properties as scaffold materials with growth factors; however,
      whether chitosan alone has osteoconductive ability is unclear. This study used
      cross-linked chitosan scaffolds for in vivo evaluation of scaffold-supported bone
      regeneration in rat calvarial defects using histopathological analysis and
      examination of alkaline phosphatase (ALP), calcium, phosphorus, and calcitonin
      serum levels. MATERIALS AND METHODS: Scaffolds were made of cross-linked
      chitosan. After the defect was filled with the scaffold, the periosteum was
      carefully repositioned and sutured to stabilize the scaffold. The effects of the
      scaffold on wound repair were examined microscopically. Morphological
      radiographic and histopathological analyses of wound repair ratios were performed
      at 3 and 4 weeks after the defects were made. RESULTS: Using the cross-linked
      chitosan biomaterial of the wounds. The amount of regenerated bone measured was
      significantly greater in the chitosan-treated group than in the control group.
      The ALP level in the chitosan group at 4 weeks was higher than at baseline and at
      the 4-week follow-up in the control group (P < 0.05). CONCLUSIONS: The results
      show that cross-linked chitosan has an osteoconductive effect on bone
      regeneration in vivo.

PMID- 29189413
TI  - Emerging role of exosomes in allorecognition and allograft rejection.
AB  - PURPOSE OF REVIEW: This article reviews recent literature on the nature of
      extracellular vesicles released by allogeneic transplants and examine their role
      in T-cell alloimmunity involved in rejection and tolerance of these grafts.
      RECENT FINDINGS: Donor cells release extracellular vesicles, including exosomes,
      after transplantation of allogeneic organs and tissues. Consequently, recipient
      APCs take up these exosomes and present donor MHC antigens on their surface (allo
      MHC cross-dressing) thus, activating some alloreactive T cells via a mechanism
      called semi-direct pathway of allorecognition. In addition, one study shows that
      exosomes carrying noninherited maternal antigens are associated with maternal
      microchimerism and tolerance in offspring. Finally, a few studies describe
      potential utilization of exosomes as modulators of alloimmunity and biomarkers of
      rejection in allotransplantation. SUMMARY: Extracellular vesicles, including
      exosomes, released by allografts contribute to recognition of donor antigens by T
      cells after allotransplantation. This occurs through cross-dressing of recipient
      APCs with donor MHC antigens and subsequent activation of T cells, a process
      called semi-direct alloreactivity. The relevance of this phenomenon in rejection
      and tolerance of allografts and the potential utilization of exosomes as
      biomarkers in transplantation are discussed.

PMID- 29189416
TI  - The Treatment Cascade in Children With Unsuppressed Viral Load-A Reality Check in
      Rural Lesotho, Southern Africa.
AB  - BACKGROUND: As per the guidelines of the World Health Organization, HIV-infected
      children who do not achieve viral suppression while under antiretroviral therapy
      (ART) receive enhanced adherence counseling (EAC) with follow-up viral load (VL).
      A persisting unsuppressed VL after EAC triggers switch to a second-line regimen.
      We describe the care cascade of children with unsuppressed VL while taking ART.
      METHODS: Children, aged <16 years, on first-line ART for >=6 months with
      unsuppressed VL (>=80 copies/mL) at first measurement were enrolled. As per
      guidelines, children/caregivers received EAC and a follow-up VL after 3 months,
      whereas those with persisting viremia despite good adherence were eligible for
      switching to second-line. Eighteen months after the first unsuppressed VL,
      outcomes were assessed. RESULTS: Of 191 children receiving a first-time VL in
      May/June 2014, 53 (28%) had unsuppressed viremia. The care cascade of these 53
      children was as follows: 49 (92%) received EAC and a follow-up VL in October 2014
      (1 died, 3 lost to follow-up). 36/49 (73%) stayed unsuppressed, but only 24 were
      switched to second-line. At 18-months follow-up, 10 (19%) were retained in care
      with suppressed VL, 26 were retained with ongoing viremia (49%), 2 (4%) had died,
      and 15 (28%) had no VL documentation. CONCLUSIONS: Only 1 of 5 children with
      unsuppressed initial VL under ART was retained in care and virally suppressed at
      18 months of follow-up. ART programs must increase the focus onto the extremely
      vulnerable care cascade in children with unsuppressed VL.

PMID- 29189417
TI  - Brief Report: Adherence Biomarker Measurements in Older and Younger HIV-Infected
      Adults Receiving Tenofovir-Based Therapy.
AB  - BACKGROUND: Concentrations of tenofovir (TFV) in hair and tenofovir diphosphate
      (TFV-DP) in dried blood spots (DBSs) as measures of cumulative exposure have been
      primarily studied in younger, HIV-uninfected individuals taking preexposure HIV
      prophylaxis. Data on these measures among older HIV-infected individuals are
      limited. METHODS: We evaluated longitudinal TFV and TFV-DP concentrations in hair
      and DBS, respectively, from HIV-infected adults. Multivariable model variables
      included age group (18-35 and 60 years and older), creatinine clearance (CrCl),
      hematocrit (TFV-DP), and gray hair color (TFV). RESULTS: Baseline hair TFV and
      DBS TFV-DP were moderately correlated [r = 0.5 (0.2 to 0.7); P = 0.001] across
      both age groups [younger (N = 23) and older (N = 22)]. In adjusted models, CrCl
      was associated with increases of 15.9% (7.4% to 25.0%); P = 0.0006, and 5.7% (
      0.2% to 11.9%); P = 0.057 for TFV in hair and TFV-DP in DBS, respectively, for
      every 20-mL/min CrCl decrease. Although older age (versus younger age) was
      univariately associated with increased TFV hair levels, older age was not
      significantly associated with higher concentrations in hair [-1.4% (-26.7% to
      32.7%); P = 0.93] or DBS [4.0% (-14.1% to 25.9%); P = 0.68] after adjustment.
      Similarly, gray color was not significantly associated with higher TFV levels in
      hair [27.6% (-11.1% to 83.0%; P = 0.18)] in adjusted models. In both adjusted and
      unadjusted models of TFV-DP levels in DBS, a 1% hematocrit increase was
      associated with a 3.3% (0.2% to 6.5%) TFV-DP increase (P = 0.04). CONCLUSIONS:
      Cumulative drug exposure measures (hair and DBS) were comparable in younger and
      older HIV-infected individuals on TFV-based therapy after adjustment for renal
      function.

PMID- 29189418
TI  - What Proportion of HIV-Infected Foreign-Born Individuals in the United States
      Have Been Infected After Immigrating to the United States?

PMID- 29189419
TI  - Procedural sedation and analgesia for adults in Europe: Safety first.

PMID- 29189420
TI  - Neostigmine-based reversal of intermediate acting neuromuscular blocking agents
      to prevent postoperative residual paralysis: A systematic review.
AB  - BACKGROUND: Neostigmine is widely used to antagonise residual paralysis. Over the
      last decades, the benchmark of acceptable neuromuscular recovery has increased
      progressively to a train-of-four (TOF) ratio of at least 0.9. Raising this
      benchmark may impact on the efficacy of neostigmine. OBJECTIVE(S): The systematic
      review evaluates the efficacy of neostigmine to antagonise neuromuscular block to
      attain a TOF ratio of at least 0.9. DESIGN: We performed a systematic search of
      the literature from January 1992 to December 2015. DATA SOURCES OR SETTING:
      PubMed, EMBASE and the Cochrane Controlled Clinical Trials database were searched
      for randomised controlled human studies. Search was performed without language
      restrictions, using the following free text terms: 'neostigmine', 'sugammadex',
      'edrophonium' or 'pyridostigmine' AND 'neuromuscular block', 'reversal' or
      'reverse'. ELIGIBILITY CRITERIA: Studies were accepted for inclusion if they used
      quantitative neuromuscular monitoring and neostigmine as the reversal agent.
      Selected trials were checked by two of the authors for data integrity. Trials
      relevant for inclusion had to report the number of patients included, the type of
      anaesthetic maintenance, the type of neuromuscular blocking agent used, the
      reversal agent and dose used, the depth of neuromuscular block when neostigmine
      was administered and the reversal time (time from injection of neostigmine until
      a TOF ratio >=0.9 was attained). RESULTS: 19 trials were eligible for
      quantitative analysis. In patients with deep residual block [T1 (first twitch
      height) <10%] 70 MUg kg neostigmine was used (five trials, 118 patients), and the
      mean reversal time was 17.1 min (95% confidence interval (CI) [12.4 to 21.8]). In
      patients with moderate residual block (T1 10% to <25%) the mean neostigmine dose
      was 56 MUg kg (seven trials, 342 patients), and the mean reversal time was 11.3
      min (95% CI [9.2 to 13.4]). In patients with a shallow residual block (T1 >= 25%)
      the mean neostigmine dose was 40 MUg kg (13 trials, 535 patients), and the mean
      reversal time was 8.0 min (95% CI [6.8 to 9.2]). CONCLUSION: Based on the
      findings of this systematic review, we recommend that the administration of
      neostigmine be delayed until an advanced degree of prereversal recovery has
      occurred (i.e. a T1 >25% of baseline), or that a recovery time longer than 15 min
      be accepted.

PMID- 29189422
TI  - Extracorporeal Membrane Oxygenation in Premature Infants With Congenital
      Diaphragmatic Hernia.
AB  - Prematurity and low birth weight have been exclusion criteria for extracorporeal
      membrane oxygenation (ECMO); however, these criteria are not evidence based. With
      advances in anticoagulation, improved technology, and surgical expertise, it is
      difficult to deny a potential therapy based on these criteria alone. We report
      the outcome of three neonates who were ineligible based on traditional criteria
      but were offered ECMO as a life-saving measure. We highlight the
      interdisciplinary nature of modern decision-making. All three neonates had severe
      congenital diaphragmatic hernia diagnosed prenatally, had normal fetal
      karyotypes, were born prematurely, and weighed less than 2 kg. All three neonates
      underwent cervical venoarterial cannulation, stabilization on ECMO, and repair of
      their congenital diaphragmatic hernia early in their ECMO courses. All three
      infants had long courses of respiratory support attributable to lung hypoplasia,
      but there were no short- or long-term complications attributable to ECMO support
      directly. All three are alive at 2 years of age and were making progress
      developmentally. In conclusion, with interdisciplinary collaboration and clinical
      guidelines uniformly implemented, low birth weight infants may benefit from ECMO
      and should not be denied the therapy arbitrarily based on gestational age or size
      alone. Further research is essential to determine appropriate patient selection
      in premature infants.

PMID- 29189421
TI  - Asenapine in the management of impulsivity and aggressiveness in bipolar disorder
      and comorbid borderline personality disorder: an open-label uncontrolled study.
AB  - Borderline personality disorder (BPD) often co-occurres with bipolar disorder
      (BD). Impulsivity and aggressiveness represent core shared features and their
      pharmacological management is mainly based on mood stabilizers and
      antipsychotics, although scarce evidence is available for this context of
      comorbidity. The aim of the present study was to evaluate the role of Asenapine
      as an adjunctive drug for reducing aggressiveness and impulsivity in a sample of
      Italian BD type I outpatients with or without a comorbid BPD. This was an
      observational 12-week open-label uncontrolled clinical study carried out from
      April to October 2014 in two psychiatric clinics in Sicily. Each patient was
      treated with asenapine at two dose options, 5 mg (twice daily) or 10 mg (twice
      daily), and concomitant ongoing medications were not discontinued. We measured
      impulsivity using the Barratt Impulsiveness Scale (BIS) and aggressiveness using
      the Aggressive Questionnaire (AQ). For the analysis of our outcomes, patients
      were divided into two groups: with or without comorbid BPD. Adjunctive therapy
      was associated with a significant decrease of BIS and AQ overall scores in the
      entire bipolar sample. Yet, there was no significant difference in BIS and AQ
      reductions between subgroups. Using a regression model, we observed that
      concomitant BPD played a negative role on the Hostility subscale and overall AQ
      score variations; otherwise, borderline co-diagnosis was related positively to
      the reduction of physical aggression. According to our post-hoc analysis, global
      aggressiveness scores are less prone to decrease in patients with a dual
      diagnosis, whereas physical aggressiveness appears to be more responsive to the
      add-on therapy in patients with comorbidity.

PMID- 29189423
TI  - The Boy in the Bubble and the Baby With the Berlin Heart: The Dangers of "Bridge
      to Decision" in Pediatric Mechanical Circulatory Support.
AB  - On the day of his birth in 1971, David Vetter was "temporarily" placed in a
      sterile isolator to wait for a bone marrow donor who would cure his Severe
      Combined Immunodeficiency Syndrome. After enduring 12 years in isolation, David,
      now known to the world as "The Boy in the Bubble", received a bone marrow
      transplant from his unmatched sister and died 4 months later. Like Severe
      Combined Immunodeficiency Syndrome, pediatric heart failure is a rare and life
      threatening condition for which organ transplantation is often the only option
      for survival. Nearly 15 years ago, the Berlin Heart EXCOR ventricular assist
      device was developed, as the isolator was for David, to be a bridge to
      transplantation for infants and children with unstable heart failure. Yet, when
      symptoms progress faster than the patient's suitability for transplant can be
      evaluated, this device may be implanted as a "bridge-to-decision" while a
      transplant evaluation is completed. Therein lies the potential for history to
      repeat itself. As biomedical science carries us ever forward in our ability to
      sustain life, we must always bear in mind that the miraculous EXCOR must not be a
      machine that simply sustains the circulation. It must be, and always remain, a
      bridge to somewhere.

PMID- 29189424
TI  - iPhone in the Management of the Berlin Heart EXCOR Ventricular Assist Device.
AB  - Berlin Heart Inc. EXCOR is an extracorporeal pneumatically pulsatile ventricular
      assist device approved for use in pediatric age group since 2011 in the United
      States. It is a well-established life-saving therapy for the bridge to heart
      transplant or to provide circulatory support in a transplanted patient. The most
      commonly reported problem was "membrane defect" in a postmarketing major device
      reporting. In general, the filling and emptying of the pump can be easily
      visualized, but the interobserver variability exist. In this first novel report,
      we used the iPhone slow motion video to quantify and compare the differences in
      filling and emptying that positively impacted the management of the Berlin Heart.
      This is an initial exploratory concept that will need further studies to validate
      this bedside tool.

PMID- 29189425
TI  - Remodeling Failing Human Myocardium With Hybrid Cell/Matrix and Transmyocardial
      Revascularization.
AB  - Given the limited treatment options for advanced heart failure, the intrinsic
      regenerative properties of stem cells have been evaluated for myocardial
      remodeling. Previous stem cells techniques for myocardiocyte remodeling have been
      limited by the low cellular retention. Presented is a hybrid approach for
      remodeling infarcted myocardium through implantation of allogeneic human amniotic
      fluid-derived mesenchymal stem cells within micronized human allograft-derived
      liquid matrix during the performance of transmyocardial revascularization (TMR).
      Given the induced increase in vascular density from TMR, we hypothesize that it
      may serve as a therapeutic delivery system for stem cell placement into damaged
      myocardium. We present a patient with ischemic cardiomyopathy and refractory
      angina, who clinically improved after this hybrid therapy of intraoperative TMR
      and placement of amniotic fluid-derived mesenchymal stem cells and liquid matrix
      within the TMR channels. Noninvasive testing of myocardial viability biomarkers
      utilizing both cardiac magnetic resonance imaging and thallium imaging supported
      the clinical improvement in cardiac symptom may be related to ventricular
      remodeling in a region of infarct with subsequent functional improvement.

PMID- 29189426
TI  - The Influence of Exercise on Cardiovascular Health in Sedentary Adults With Human
      Immunodeficiency Virus.
AB  - BACKGROUND: Lifestyle physical activity (ie, moderate physical activity during
      routine daily activities most days of the week) may benefit human
      immunodeficiency virus (HIV)-positive adults who are at high risk for
      cardiovascular disease. OBJECTIVE: The aims of this study were to describe
      lifestyle physical activity patterns in HIV-positive adults and to examine the
      influence of lifestyle physical activity on markers of cardiovascular health. Our
      secondary objective was to compare these relationships between HIV-positive
      adults and well-matched HIV-uninfected adults. METHODS: A total of 109 HIV
      positive adults and 20 control participants wore an ActiGraph accelerometer,
      completed a maximal graded cardiopulmonary exercise test, completed a coronary
      computed tomography, completed anthropomorphic measures, and had lipids and
      measures of insulin resistance measured from peripheral blood. RESULTS:
      Participants (N = 129) had a mean age of 52 +/- 7.3 years, 64% were male (n =
      82), and 88% were African American (n = 112). On average, HIV-positive
      participants engaged in 33 minutes of moderate-to-vigorous physical activity per
      day (interquartile range, 17-55 minutes) compared with 48 minutes in controls
      (interquartile range, 30-62 minutes, P = .05). Human immunodeficiency virus
      positive adults had poor fitness (peak oxygen uptake [VO2], 16.8 +/- 5.2 mL/min
      per kg; and a ventilatory efficiency, 33.1 [4.6]). A marker of HIV disease
      (current CD4+ T cell) was associated with reduced peak VO2 (r = -0.20, P < .05)
      and increased insulin resistance (r = 0.25, P < .01) but not with physical
      activity or other markers of cardiovascular health (P >= 0.05). After controlling
      for age, gender, body mass index, and HIV status, physical activity was not
      significantly associated with peak VO2 or ventilatory efficiency. CONCLUSION:
      Human immunodeficiency virus-positive adults have poor physical activity patterns
      and diminished cardiovascular health. Future longitudinal studies should examine
      whether HIV infection blunts the beneficial effects of physical activity on
      cardiovascular health.

PMID- 29189427
TI  - Self-efficacy Mediates the Relationship Between Motivation and Physical Activity
      in Patients With Heart Failure.
AB  - BACKGROUND: Motivation is necessary in patients with heart failure (HF) who are
      attempting to become more physically active but may not be sufficient to initiate
      physical activity. Self-efficacy might explain the relationship between
      motivation and physical activity. OBJECTIVE: The aim of this study was to examine
      the role of exercise self-efficacy in the relationship between exercise
      motivation and physical activity in patients with HF. METHODS: A total of 100
      stable patients with HF (88% in New York Heart Association class II/III; mean
      age, 67 +/- 13 years; 62% men) were studied. Self-efficacy was measured with the
      Exercise Self-Efficacy Scale; motivation, with the Exercise Motivation Index; and
      physical activity, with a self-report questionnaire. Logistic regression analyses
      were made to examine the mediation effect of exercise self-efficacy on the
      relationship between exercise motivation and physical activity. RESULTS: Forty
      two percent of the 100 patients reported engaging in less than 60 minutes per
      week of physical activity. Motivation predicted physical activity (b = 0.58, P <
      .05), but after controlling for self-efficacy, the relationship between
      motivation and physical activity was no longer significant (b = 0.76, P = .06),
      indicating full mediation. CONCLUSION: Motivation to be physically active is
      important but not sufficient. In addition to a high level of motivation to be
      physically active, it is important that patients with HF have a high degree of
      self-efficacy.

PMID- 29189428
TI  - Wake-up Call to Clinicians: The Impact of Sleep Dysfunction on Gastrointestinal
      Health and Disease.
AB  - Sleep dysfunction is an epidemic affecting a large portion of the adult
      population. Recent studies have linked sleep dysfunction with an upregulation of
      proinflammatory cytokines (eg, tumor necrosis factor-alpha, interleukin-1 and
      interleukin-6), the implications of which can have a profound impact on a variety
      of gastrointestinal disease. In particular, sleep dysfunction seems to accelerate
      disease states characterized by inflammation (eg, gastroesophageal reflux
      disease, irritable bowel syndrome and functional dyspepsia, chronic liver
      disease, inflammatory bowel disease, and colorectal cancer). This article
      evaluates the complex interplay between sleep dysfunction and gastrointestinal
      health and disease.

PMID- 29189429
TI  - New developments in immunotherapy for pediatric solid tumors.
AB  - PURPOSE OF REVIEW: Building upon preclinical advances, we are uncovering
      immunotherapy strategies that are translating into improved outcomes in tumor
      subsets. Advanced pediatric solid tumors carry poor prognoses and resultant
      robust efforts to apply immunotherapy advances to pediatric solid tumors are in
      progress. Here, we discuss recent developments in the field using mAb and mAb
      based therapies including checkpoint blockade and chimeric antigen receptors
      (CARs). RECENT FINDINGS: The pediatric solid tumor mAb experience targeting the
      diganglioside, GD2, for patients with neuroblastoma has been the most compelling
      to date. GD2 and alternative antigen-specific mAbs are now being incorporated
      into antibody-drug conjugates, bispecific antibodies and CARs for treatment of
      solid tumors. CARs in pediatric solid tumors have not yet achieved comparative
      responses to the hematologic CAR experience; however, novel strategies such as
      bispecific targeting, intratumoral administration and improved understanding of T
      cell biology may yield enhanced CAR-efficacy. Therapeutic effect using single
      agent checkpoint blocking antibodies in pediatric solid tumors also remains
      limited to date. Combinatorial strategies continue to hold promise and the
      clinical effect in tumor subsets with high antigenic burden is being explored.
      SUMMARY: Pediatric immunotherapy remains at early stages of translation, yet we
      anticipate that with advanced technology, we will achieve widespread, efficacious
      use of immunotherapy for pediatric solid tumors.

PMID- 29189430
TI  - Precision medicine in pediatric oncology.
AB  - PURPOSE OF REVIEW: The current review describes recent advances and unique
      challenges in precision medicine for pediatric cancers and highlights clinical
      trials assessing the clinical impact of targeted therapy matched to molecular
      alterations identified by tumor profiling. RECENT FINDINGS: Multiple prospective
      clinical sequencing studies in pediatric oncology have been reported in the last
      2 years. These studies demonstrated feasibility of sequencing in the clinic and
      revealed a rate of actionable variants that justifies the development of
      precision trials for childhood cancer. A number of precision medicine trials are
      recently completed, underway or in development and these will be reviewed herein,
      with a focus on highlighting aspects of precision medicine trial design relevant
      to pediatric oncology. SUMMARY: The primary results of the first round of
      pediatric precision oncology clinical trials will provide us with a greater
      understanding of the clinical impact of linking tumor profiling to selection of
      targeted therapies. The aggregation of sequencing and clinical data from these
      trials and the results of biologic investigations linked to these trials will
      drive further discoveries and broaden opportunities for precision medicine for
      children with cancer.

PMID- 29189432
TI  - The South African English Smartphone Digits-in-Noise Hearing Test: Effect of Age,
      Hearing Loss, and Speaking Competence.
AB  - OBJECTIVES: This study determined the effect of hearing loss and English-speaking
      competency on the South African English digits-in-noise hearing test to evaluate
      its suitability for use across native (N) and non-native (NN) speakers. DESIGN: A
      prospective cross-sectional cohort study of N and NN English adults with and
      without sensorineural hearing loss compared pure-tone air conduction thresholds
      to the speech reception threshold (SRT) recorded with the smartphone digits-in
      noise hearing test. A rating scale was used for NN English listeners' self
      reported competence in speaking English. This study consisted of 454 adult
      listeners (164 male, 290 female; range 16 to 90 years), of whom 337 listeners had
      a best ear four-frequency pure-tone average (4FPTA; 0.5, 1, 2, and 4 kHz) of <=25
      dB HL. RESULTS: A linear regression model identified three predictors of the
      digits-in-noise SRT, namely, 4FPTA, age, and self-reported English-speaking
      competence. The NN group with poor self-reported English-speaking competence
      (<=5/10) performed significantly (p < 0.01) poorer than the N and NN (>=6/10)
      groups on the digits-in-noise test. Screening characteristics of the test
      improved with separate cutoff values depending on English-speaking competence for
      the N and NN groups (>=6/10) and NN group alone (<=5/10). Logistic regression
      models, which include age in the analysis, showed a further improvement in
      sensitivity and specificity for both groups (area under the receiver operating
      characteristic curve, 0.962 and 0.903, respectively). CONCLUSIONS: Self-reported
      English-speaking competence had a significant influence on the SRT obtained with
      the smartphone digits- in-noise test. A logistic regression approach considering
      SRT, self-reported English-speaking competence, and age as predictors of best ear
      4FPTA >25 dB HL showed that the test can be used as an accurate hearing screening
      tool for N and NN English speakers. The smartphone digits-in-noise test,
      therefore, allows testing in a multilingual population familiar with English
      digits using dynamic cutoff values that can be chosen according to self-reported
      English-speaking competence and age.

PMID- 29189431
TI  - Psychosocial Outcomes in Long-Term Cochlear Implant Users.
AB  - OBJECTIVES: The objectives of this study were to investigate psychosocial
      outcomes in a sample of prelingually deaf, early-implanted children, adolescents,
      and young adults who are long-term cochlear implant (CI) users and to examine the
      extent to which language and executive functioning predict psychosocial outcomes.
      DESIGN: Psychosocial outcomes were measured using two well-validated, parent
      completed checklists: the Behavior Assessment System for Children and the Conduct
      Hyperactive Attention Problem Oppositional Symptom. Neurocognitive skills were
      measured using gold standard, performance-based assessments of language and
      executive functioning. RESULTS: CI users were at greater risk for clinically
      significant deficits in areas related to attention, oppositional behavior,
      hyperactivity-impulsivity, and social-adaptive skills compared with their normal
      hearing peers, although the majority of CI users scored within average ranges
      relative to Behavior Assessment System for Children norms. Regression analyses
      revealed that language, visual-spatial working memory, and inhibition
      concentration skills predicted psychosocial outcomes. CONCLUSIONS: Findings
      suggest that underlying delays and deficits in language and executive functioning
      may place some CI users at a risk for difficulties in psychosocial adjustment.

PMID- 29189433
TI  - Transintestinal cholesterol excretion in humans.
AB  - PURPOSE OF REVIEW: To discuss recent insights into the measurement and cellular
      basis of transintestinal cholesterol excretion (TICE) in humans and to explore
      TICE as a therapeutic target for increasing reverse cholesterol transport. RECENT
      FINDINGS: TICE is the net effect of cholesterol excretion by the enterocyte into
      the intestinal lumen and is the balance between input and output fluxes through
      the enterocytes. These fluxes are: cholesterol excretion into the intestinal
      lumen mainly via ATP-binding cassette (ABC) G5/8, cholesterol absorption from the
      intestine by Niemann-Pick C1 like protein 1, the uptake of plasma lipoproteins by
      enterocytes at the basolateral membrane, and the excretion of cholesterol in
      chylomicrons into the lymph. Multiple studies have shown that TICE contributes to
      fecal neutral sterol (FNS) excretion in humans. TICE can be targeted with plant
      sterols, liver X receptor agonists, bile acids, ezetimibe, and proprotein
      convertase subtilisin/kexin type 9 inhibitors. SUMMARY: TICE contributes
      significantly to FNS excretion in humans, independently of the biliary pathway.
      Knowledge about its underlying cellular mechanisms surges through in-vivo and in
      vitro studies in mice and humans. TICE might be an interesting therapeutic target
      for increasing cholesterol disposal with the feces. Albeit multiple therapeutic
      options are available, studies showing clinical benefit are still needed.

PMID- 29189435
TI  - Investigating Physicians' Views on Soft Signals in the Context of Their Peers'
      Performance.
AB  - BACKGROUND: Physicians are responsible for delivering high quality of care. In
      cases of underperformance, hindsight knowledge indicates forewarning being
      potentially available in terms of concerns, signs, or signals. It is not known
      how the physicians involved perceive such signals. PURPOSE: To openly explore how
      physicians perceive soft signals and react on them. METHODS: In-depth interviews
      with 12 hospital-based physicians from various specialties and institutions
      following the interpretative phenomenological analysis approach. RESULTS:
      Physicians perceive soft signals as an observable deviation from a colleague's
      normal behavior, appearance, or communication. Once observed, they evaluate the
      signal by reflecting on it personally and/or by consulting others, resulting in
      either an active (i.e., speaking up) or passive (i.e., avoidance) reaction.
      Observer sensitivity, closeness to the peer, and cohesion of the physician group
      influence this observation-evaluation-reaction process. CONCLUSIONS AND
      IMPLICATIONS: Physicians perceive soft signals as indicators of well-being and
      collegiality, not as concerns about performance or patient safety. They feel it
      is their responsibility to be sensitive to and deal with expressed signals.
      Creating a psychological safe culture could foster such an environment. Because a
      threat to physicians' well-being may indirectly affect their professional
      performance, soft signals require serious follow-up.

PMID- 29189436
TI  - Offering eConsult to Family Physicians With Patients on a Pain Clinic Wait List:
      An Outreach Exercise.
AB  - Wait times for many chronic pain programs in Canada range from 6 months to 2
      years. This project sought to determine the interest of primary care providers
      (PCPs) in using an electronic consult system for patient(s) waiting for a pain
      consultation. This cross-sectional study was conducted at the pain clinic of a
      Canadian tertiary academic health sciences center. Participants were PCPs who had
      submitted a referral to this clinic. Referrals received between April 1, 2012,
      and March 31, 2014, were reviewed to determine their appropriateness for
      eConsult, and a letter providing information about eConsult and encouraging its
      use was sent to the referring PCP. Of the 585 referrals that were reviewed, 227
      were appropriate for eConsult. Fifty-one (26%) of the 194 PCP responses received
      were positive. Technologies like eConsult may help address the growing demand for
      specialist advice. In addition to facilitating response to specific questions,
      the bidirectional nature of eConsult permits its use for educating PCPs about
      chronic pain treatment. Given that almost one third of responding PCPs indicated
      an interest in eConsult, its potential reach is vast. Additional study is needed
      to understand barriers to PCP acceptance and use of eConsult and the uptake of
      advice given.

PMID- 29189437
TI  - Postoperative Respiratory Failure.

PMID- 29189438
TI  - Perioperative Fluid Strategies to Prevent Lung Injury.

PMID- 29189439
TI  - Leading Causes of Anesthesia-Related Liability Claims in Ambulatory Surgery
      Centers.
AB  - OBJECTIVE: We present a contemporary analysis of patient injury, allegations, and
      contributing factors of anesthesia-related closed claims, which involved cases
      that specifically occurred in free-standing ambulatory surgery centers (ASCs).
      METHODS: We examined ASC-closed claims data between 2007 and 2014 from The
      Doctors Company, a medical malpractice insurer. Findings were coded using the
      Comprehensive Risk Intelligence Tool developed by CRICO Strategies. We compared
      coded data from ASC claims with hospital operating room (HOR) claims, in terms of
      injury severity category, nature of injury, nature of allegation, contributing
      factors identified, and contributing comorbidities and claim value. RESULTS:
      Ambulatory surgery center claims were more likely to be classified as medium
      severity than HOR claims, more likely to involve dental damage or pain than HOR
      claims, but less likely to involve death or respiratory or cardiac arrest.
      Technical performance was the most common contributing factor: 47% of ASCs and
      48% of HORs. Only 7% of allegations relating to technical performance were judged
      to be a direct result of poor technical performance. The most common anesthesia
      procedures resulting in ASC claims were injection of anesthesia into a peripheral
      nerve (34%) and intubation (29%). Obesity was the most common contributing
      comorbidity in both settings. Mean closed claim value was significantly lower for
      ASC than HOR claims, averaging US $87,888 versus $107,325. CONCLUSIONS: Analysis
      of ASC and HOR claims demonstrates significant differences and several common
      sources of liability. These include improving strategies for thorough screening,
      preoperative assessment and risk stratifying of patients, incorporating routine
      dental and airway assessment and documentation, diagnosing and treating
      perioperative pain adequately, and improving the efficacy of communication
      between patients and care providers.

PMID- 29189440
TI  - Patient Safety Activity Under the Social Insurance Medical Fee Schedule in Japan:
      An Overview of the 2010 Nationwide Survey.
AB  - OBJECTIVES: Little is known about patient safety performance under the social
      insurance medical fee schedule in Japan. The Health Ministry in Japan introduced
      the preferential patient safety countermeasure fee (PPSCF) to promote patient
      safety in 2006 and revised the PPSCF system in 2010. This study aims to address
      the patient safety performance status at hospitals implementing the PPSCF.
      METHODS: A nationwide questionnaire survey targeting 2674 hospitals with the
      PPSCF was performed in 2010 to 2011. The 627 participant hospitals were divided
      into the following three groups: 178 hospitals implementing PPSCF 1 with 400 beds
      or more (group A), 286 hospitals implementing PPSCF 1 with 399 beds or fewer
      (group B), and 163 hospitals implementing PPSCF 2 (group C). RESULTS: The mean
      numbers (standard errors) of patient safety managers were 1.45 (0.07) in group A,
      1.12 (0.04) in group B, and 0.37 (0.12) in group C (P < 0.001). The participation
      number and rates of all staff for the patient safety seminar were 1721 (167) and
      1.64 (0.10) in group A, 580 (26) and 1.94 (0.09) in group B, and 349 (31) and
      1.98 (0.17) in group C (P < 0.001, P = 0.105).These results can be explained
      because hospitals with PPSCF 1 (groups A and B) must assign at least one full
      time patient safety manager, whereas hospitals with PPSCF 2 (group C) are not
      required to do so. Patient safety performance at hospitals with PPSCF 1 was more
      active than that at hospitals with PPSCF 2. However, when the values were
      converted to per capita or per 100 beds, there were no differences across the
      three groups. CONCLUSIONS: The PPSCF encourages hospitals to perform actions for
      patient safety by providing incentives under the social insurance medical fee
      schedule in Japan.

PMID- 29189441
TI  - Biomechanical and Clinical Comparison of Suture Techniques in Arthroscopic
      Rotator Cuff Repair.

PMID- 29189442
TI  - Effect of postoperative radiotherapy on outcome in resectable stage IIIA-N2 non
      small-cell lung cancer: an updated meta-analysis.
AB  - BACKGROUND: In a previous meta-analysis-based modeling study, it was hypothesized
      that modern postoperative radiotherapy (PORT) may improve both local recurrence
      and overall survival (OS) in stage IIIA-N2 non-small-cell lung cancer (NSCLC).
      There were only four single-arm trials with a total of 357 patients. As other
      trials have provided new and controversial data, we performed this updated meta
      analysis to test the hypothesis. PATIENTS AND METHODS: Systematic reviews in
      Medline, Cochrane, and Science Direct up to December 2015 identified publications
      exploring the efficacy of PORT in resectable stage IIIA-N2 NSCLC. RESULTS:
      Overall, 16 trials comprising 3278 patients were included. There was a
      significant benefit in favor of PORT regarding OS [hazard ratio (HR): 0.73, 95%
      confidence interval (CI): 0.58-0.92, P=0.008; absolute benefit at 5 years=8%],
      disease-free survival (HR: 0.70, 95% CI: 0.60-0.83, P<0.0001), and locoregional
      recurrence-free survival (HR: 0.37, 95% CI: 0.24-0.58, P<0.0001). Restriction of
      the analysis to trials with induction and/or adjuvant chemotherapy led to similar
      results. PORT significantly decreased the risk of local recurrence (risk ratio:
      0.64, 95% CI: 0.50-0.82, P=0.0006) and DM (risk ratio: 0.74, 95% CI: 0.62-0.88,
      P=0.0005), and the absolute risk differences were 13 and 14%, respectively.
      CONCLUSION: The addition of PORT, with or without chemotherapy, significantly
      improves local control and survival in patients with resectable stage IIIA-N2
      NSCLC.

PMID- 29189443
TI  - Post-therapy lesions in patients with non-Hodgkin's lymphoma characterized by 18F
      FDG PET/CT-guided biopsy using automated robotic biopsy arm.
AB  - PURPOSE: The aim of this study was to analyse the positive predictive value (PPV)
      of post-therapy fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT performed for
      response or recurrence evaluation in patients with non-Hodgkin's lymphoma (NHL)
      and to appraise the diagnostic utility of F-FDG PET/CT-guided biopsy in this
      setting. PATIENTS AND METHODS: A total of 17 patients with NHL showing F-FDG avid
      lesions in F-FDG PET/CT performed for response or recurrence assessment underwent
      F-FDG PET/CT-guided biopsy using automated robotic biopsy arm needle navigation
      technique. The objectives were analysed in reference to histopathology. RESULTS:
      In all, 15 of the 17 (88.5%) procedures yielded adequate representative tissue
      samples. Nine out of 15 lesions were positive for residual disease and the
      remaining revealed benign findings on histopathology. One patient with
      inconclusive biopsy underwent surgical resection and histopathology confirmed the
      presence of residual disease. PPV of theF-FDG PET/CT was observed to be 62.5%
      (10/16). CONCLUSION: F-FDG PET/CT for response evaluation in NHL possesses a low
      PPV and hence warrants histopathological correlation when F-FDG PET/CT findings
      influence management decision. Diagnostic yield of F-FDG PET/CT-guided biopsy is
      high and has the potential to reduce sampling errors.

PMID- 29189444
TI  - The clinical value of PET and PET/CT in the diagnosis and management of suspected
      cervical cancer recurrence.
AB  - The aim of this study was to evaluate the clinical value of PET and PET/CT in
      suspected recurrent cervical cancer. The recurrence of cervical cancer has a poor
      prognosis. Earlier intervention would lead to a better prognosis. PET and PET/CT
      were promising in early diagnosis of recurrence because they could detect the
      biological and molecular changes before the anatomical size changes occurred.
      However, few data concerning the clinical effect of PET and PET/CT were
      available. The database for PET (or positron emission tomography or FDG or
      fluorodeoxyglucose) AND cervical cancer (or cervical tumor or cervical neoplasm
      or cervical carcinoma) AND recurrence or relapse was searched. The diagnostic
      value of PET or PET/CT was evaluated in both person-based and region-based
      analyses. Seventeen studies with 707 cases were included in the meta-analysis.
      For patients who were suspected of cervical cancer recurrence, the pooled
      sensitivity of PET and PET/CT was 0.97 (0.95-0.99). For patients who were
      suspected of relapse owing to elevated squamous cell carcinoma antigen, the
      pooled sensitivity was 0.99 (0.93-1.00). Moreover, the region-based diagnostic
      value in lung, mediastinum, liver/spleen, inguinal lymph node, supraclavicular
      lymph node, and para-aortic lymph node was high, from which we can see that PET
      and PET/CT had a favorable diagnostic value on distant metastasis. In addition,
      57% of the therapeutic plans were modified owing to PET and PET/CT. PET and
      PET/CT are valuable tools in suspected recurrence of cervical cancer and provide
      valuable information for treatment decisions.

PMID- 29189445
TI  - Waging the War on Clinical Grade Inflation: The Ongoing Quest.
AB  - This study examined the presence of grade inflation in clinical courses 9 years
      after implementing strategies to improve grading precision. A comparison of
      clinical grades for cohort I (1997-2002) with cohort II (2009-2016) showed
      statistically lower grades in 2 courses (Adult 1 and Maternity) for cohort II.
      Suggestions for changing the way clinical experiences are planned, executed, and
      evaluated are provided.

PMID- 29189446
TI  - A National Study of School Counselors' Perceptions of the Nursing Profession.
AB  - School counselors are uniquely poised to influence career development among
      middle and high school students interested in nursing. This study examined 204
      school counselors' perceptions about nursing and secondary educational
      preparation. Despite national and local efforts to increase enrollment in
      baccalaureate and higher nursing programs, counselors remain unaware of the need
      for increased education in nursing. Nurse educators need to align with school
      counselors to adequately prepare students interested in nursing as a health
      career.

PMID- 29189447
TI  - Effects of a Peer Evaluation Technique on Nursing Students' Anxiety Levels.
AB  - Techniques to help decrease students' stress and anxiety during a nursing program
      can be beneficial to their overall health and mental well-being. A quasi
      experimental design was used to examine if a peer evaluation technique during
      clinical skill practice sessions decreases anxiety prior to skill performance
      evaluation with nursing faculty. Participant feedback supports the integration of
      a peer evaluation technique when learning clinical skills.

PMID- 29189448
TI  - Tumor Boost Using External Beam Radiation in Cervical Cancer Patients Unable to
      Receive Intracavitary Brachytherapy: Outcome From a Multicenter Retrospective
      Study (Korean Radiation Oncology Group 1419).
AB  - PURPOSE: We conducted this study to evaluate the outcomes of external-beam
      radiotherapy tumor boost (EBRT-B) in cervical cancer patients who could not
      receive intracavitary brachytherapy. METHODS: A total of 11 hospitals provided
      the data of patients who received EBRT-B during the period from January 2005
      through October 2012. RESULTS: A total of 75 patients were included. The median
      radiotherapy dose was 46 Gy (range, 40-54 Gy) for whole pelvis and 24 Gy (range,
      9-35 Gy) for EBRT-B. Initial tumor responses assessed at 2 to 6 months after
      radiotherapy were as follows: 46 with complete response, 22 with partial
      response, 2 with stable disease, and 3 with progressive disease. After a median
      follow-up time of 33 months, 30 patients (40.0%) showed disease progression
      including 21 (28.0%) with local progression. The 5-year local failure-free
      survival rate was 70.0%. Achieving complete response at the first follow-up visit
      and an overall treatment time of 53 days or less were significantly related to
      favorable local failure-free survival. The rate of grade 3 or higher toxicity was
      2.6%. CONCLUSIONS: Approximately 70% of patients had local tumor control after
      curative radiotherapy using EBRT-B. Early tumor response and overall treatment
      time of 53 days or less were closely associated with favorable local control.

PMID- 29189450
TI  - Letters.

PMID- 29189449
TI  - Preoperative Serum Thymidine Kinase Activity as Novel Monitoring, Prognostic, and
      Predictive Biomarker in Pancreatic Cancer.
AB  - OBJECTIVE: The aim of the study was to investigate serum thymidine kinase 1 (S
      TK) activity as a diagnostic and prognostic marker for patients with pancreatic
      ductal adenocarcinoma (PDAC). METHODS: Using the sensitive TK activity assay
      DiviTum, preoperative serum samples from 404 PDAC, 28 chronic pancreatitis, and
      25 autoimmune pancreatitis patients and 83 healthy volunteers were analyzed. The
      preoperative S-TK activities of 54 PDAC patients who received neoadjuvant therapy
      (nTx) were also compared with those of 258 PDAC patients who did not receive nTx.
      RESULTS: The preoperative S-TK activities of PDAC patients were significantly
      higher and discriminatory from autoimmune and chronic pancreatitis patients and
      control groups. The S-TK activity in PDAC patients was associated with overall
      survival. Patients with S-TK activity of less than 80 Du (DiviTum units)/L
      demonstrated median survival of 20.3 months with an estimated 18.0% 5-year
      survival rate; for S-TK activity of 80 Du/L or greater, median survival was 15.1
      months with a 6.8% 5-year survival rate. For early-stage PDAC, these differences
      were even more pronounced. The S-TK activity in the nTx group was significantly
      higher than that in the group not receiving nTx. CONCLUSIONS: Pancreatic ductal
      adenocarcinomas reveal a significant increase in S-TK activity, which is
      associated with overall survival, especially in early tumor stages. Serum
      thymidine kinase 1 activity may be a useful parameter for monitoring nTx
      efficacy.

PMID- 29189452
TI  - Responding to parents who refuse childhood immunizations.

PMID- 29189453
TI  - What's the Stop the Bleed Campaign?

PMID- 29189454
TI  - Dealing with patient self-triage.

PMID- 29189455
TI  - Growing specialty area exposure with an undergraduate perioperative nursing
      course.

PMID- 29189459
TI  - Florence Nightingale: Lighting the way for the future of nursing.

PMID- 29189460
TI  - The night shift: Follow the evidence to survive and thrive.

PMID- 29189461
TI  - When disaster strikes, will you be ready?

PMID- 29189462
TI  - Communication strategies for patients with dementia.

PMID- 29189463
TI  - How can policy change guide nursing practice to reduce in-patient falls?

PMID- 29189464
TI  - Partner with IT to reduce frustration, improve patient care.

PMID- 29189466
TI  - 59 clicks in the EHR.

PMID- 29189467
TI  - Student Perceptions of Clinical Instructor Characteristics Affecting Clinical
      Experiences.
AB  - AIM: The purpose of this study was to explore and describe students' perceptions
      of clinical instructor characteristics that affect their clinical experiences.
      BACKGROUND: Clinical instructors can have a profound impact on student clinical
      experiences, yet little is known about what clinical instructor characteristics
      promote and hinder quality clinical experiences from the student perspective.
      METHOD: A multisite prospective, descriptive exploratory design was used.
      RESULTS: Students ranked instructor knowledge and support as the highest
      desirable characteristics, followed by patience, creating challenges, enthusiasm,
      and organization. Emerging themes from the content analysis revealed that the
      ability of the instructor to convey knowledge, demonstrate professionalism, and
      exhibit enthusiasm and caring were key characteristics that influence the
      clinical experience. CONCLUSION: Nurse educators can use the results of this
      study to target hiring and placing of desired characteristics of clinical
      instructors and to support mentoring programs that promote clinical teaching
      excellence.

PMID- 29189468
TI  - Association of diastolic blood pressure with cardiovascular events in older
      people varies upon cardiovascular history.
AB  - BACKGROUND: In older age, a low DBP has been associated with increased risk of
      cardiovascular events, especially in frail older people. We tested the hypothesis
      that low DBP is associated with a high risk of cardiovascular events in people
      with a previous history of cardiovascular disease, as a proxy of vascular
      impairment. METHODS: We included 5804 participants (mean age 75 years) from the
      PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) who as part of
      the trial were intensively monitored for an average period of 3.2 years. DBP was
      categorized in low (<70 mmHg), normal (70-90 mmHg) or high (>90 mmHg). Cox
      proportional hazards analyses were used to estimate hazard ratio with 95%
      confidence intervals (CI); analyses were stratified for cardiovascular history.
      RESULTS: Participants with low DBP had a 1.24-fold (1.04; 1.49) increased risk of
      cardiovascular events compared with those with normal DBP. After further
      adjusting for cardiovascular factors, this association attenuated to 1.05 (0.86;
      1.28). A previous history of cardiovascular disease significantly modified the
      relation between DBP and risk of cardiovascular events (P-interaction 0.042). In
      participants without a history of cardiovascular disease, DBP was marginally
      significantly associated with an increased event risk (hazard ratio (95% CI) per
      10 mmHg increase in DBP 1.08 (0.99; 1.18), P value = 0.07), whereas in
      participants with a history of cardiovascular disease, higher DBP was associated
      with a decreased risk of cardiovascular events (hazard ratio (95% CI) per 10 mmHg
      increase in DBP 0.92 (0.85; 0.99, P value = 0.018). These risk estimates were
      independent of potential confounders, including classical cardiovascular risk
      factors. CONCLUSION: The association of DBP with cardiovascular events in older
      people varies upon their previous history, showing that in participants with
      preexisting cardiovascular diseases, a higher DBP associates with a decreased
      risk of future cardiovascular events.

PMID- 29189470
TI  - Examining the Likelihood of Experiencing Productivity Loss and Receiving Social
      Security Disability Income Following the Onset of Chronic Disease.
AB  - OBJECTIVE: The aim of the study was to examine the likelihood of reporting
      productivity loss and receiving social security disability (SSD) income following
      a chronic health condition diagnosis using a longitudinal panel design. METHODS:
      Using the Panel Study of Income Dynamics, logistic regression analyses were
      conducted to estimate the likelihood of reporting productivity loss or receiving
      SSD following the diagnosis of arthritis, cancer, psychological problems, or
      heart conditions. Respondents reporting a new diagnosis of a condition were
      matched with five similarly aged respondents not reporting a diagnosis. RESULTS:
      For all conditions except cancer, the odds of reporting productivity loss and
      receiving SSD increased at both the wave where the condition was first reported
      and 2 years after for respondents reporting a condition compared with those not
      reporting a condition. CONCLUSIONS: The onset of chronic disease increases the
      likelihood of experiencing productivity loss and receiving SSD.

PMID- 29189469
TI  - Social Relations at Work and Incident Dementia: 29-Years' Follow-Up of the
      Copenhagen Male Study.
AB  - OBJECTIVE: We investigated whether social relations at work were associated with
      incident dementia in old age. METHODS: One thousand five hundred seventy-two
      occupationally active men from the Copenhagen Male Study Cohort were followed
      from 1986 to 2014. Participants underwent a clinical examination at baseline and
      answered questionnaires on whether they (1) had possibilities to be in contact
      with coworkers, (2) could get along with coworkers, and (3) were satisfied with
      supervisor. Poisson regression was used to estimate incidence rate ratios (IRR).
      RESULTS: Two hundred forty five (15.6%) men were diagnosed with dementia during
      an average of 15.8 years of follow-up. After adjusting for potential confounders,
      limited contact with coworkers was associated with a higher risk of dementia (IRR
      = 2.49, 95% confidence interval [CI] 1.14 to 5.44), but the other two measures
      were not. CONCLUSIONS: Our data partially support that social relations at work
      are associated with incident dementia.

PMID- 29189471
TI  - A Novel Approach to Reducing Workers Compensation Costs in a Multicenter Hospital
      System.
AB  - OBJECTIVE: To evaluate the efficacy of an injury prevention and monitoring
      program implemented by athletic trainers to reduce workers compensation costs in
      a hospital system with multiple centers and locations. METHODS: A retrospective
      analysis of workers compensation claims (ie, lost days, light days, and incurred
      costs) was performed to compare injury data from 2 years before to 2 years after
      the start of the program. RESULTS: The program significantly reduced the
      organization's incurred costs by 46.7% (P = 0.031) and light days by 44% (P =
      0.022). Lost days were found to decrease by 37%, however, this decrease was not
      statistically significant (P = 0.078). CONCLUSIONS: Athletic trainers, using
      their knowledge of anatomy, biomechanics, ergonomics, injury management, and
      rehabilitation, can effectively prevent and reduce workers compensation costs in
      a multicenter hospital system.

PMID- 29189472
TI  - SIRT2 and Akt mediate NAD+-induced and NADH-induced increases in the
      intracellular ATP levels of BV2 microglia under basal conditions.
AB  - NAD replenishment can restore ATP levels and rescue premature aging in Cockayne
      syndrome mice. However, there has been no mechanistic study regarding the effects
      of NAD and NADH on intracellular ATP levels under basal conditions. In our
      current study, we used BV2 microglia to test our hypothesis that NAD and NADH can
      increase intracellular ATP levels under basal conditions. We found that both NAD
      and NADH significantly increased the intracellular ATP levels of BV2 microglia,
      which were attenuated by SIRT2 siRNA, the SIRT2 inhibitor AGK2, and the
      phosphatidylinositol 3-kinase/Akt inhibitor LY294002. Our study has also
      suggested that SIRT2 mediates the NAD-induced and NADH-induced increase in Akt
      phosphorylation in BV2 microglia. Collectively, our study has suggested that
      SIRT2 mediates both NAD-induced and NADH-induced increases in the intracellular
      ATP levels of BV2 microglia by modulating Akt phosphorylation.

PMID- 29189473
TI  - The anger expression trait affects conflict monitor: a Go/No-go event-related
      potential study.
AB  - The Anger-Out and Anger-In is the emotional expression of anger in two main ways.
      To explore the time course of inhibitory control in individuals with different
      anger expression trait, we recorded and analyzed event-related potential data
      relevant to the Go/No-go task. Although the No-go effect of P3 closely related to
      the actual inhibition of the motor system was similar between two groups, the No
      go effect of N2 related to conflict monitoring was smaller in the Anger-In than
      that in the Anger-Out group. These data suggest the reduced early stage of
      inhibitory processes in Anger-In individuals, implicating the dysfunction of
      conflict monitoring and providing new electrophysiological evidence for the
      theory of anger expression.

PMID- 29189474
TI  - Pediatric ACL Reconstruction and Return to the Operating Room: Revision is Less
      Than Half of the Story.
AB  - BACKGROUND: Although there are several causes of unplanned return to the
      operating room (RTOR) following pediatric anterior cruciate ligament (ACL)
      reconstruction (ACLR), prior outcomes studies focus primarily on the risk of
      graft failure. We sought to comprehensively describe indications for RTOR in
      pediatric primary ACLR patients, estimate associated rates of RTOR, and assess
      the impact of concomitant meniscal procedures on these rates. METHODS: This
      retrospective cohort study considered patients who underwent primary ACLR at an
      urban, pediatric tertiary care hospital between 2013 and 2015. Cohorts were
      defined based on the presence or absence of a concomitant surgical meniscal
      procedure with the index ACLR. The primary outcome was RTOR for an indication
      pertaining to ACLR or a potential predilection for knee injury. Cases of RTOR
      were cataloged and classified according to indication. Survival analyses were
      performed using the Kaplan-Meier estimation and competing-risks regression.
      Comparisons of any-cause RTOR rates were done using log-rank tests. RESULTS:
      After exclusion criteria were applied, 419 subjects were analyzed. RTOR
      indications were organized into 5 categories. The overall rate for any RTOR by 3
      years after surgery was 16.5%. Graft failure and contralateral ACL tear were the
      most common indications for RTOR, with predicted rates of 10.3% and 7.1%,
      respectively. ACL graft failure accounted for less than half of RTOR cases
      cataloged. Patients who had a concomitant meniscus procedure had lower rates of
      RTOR. CONCLUSIONS: Approximately 1 in 6 pediatric ACLR patients underwent >=1
      repeat surgery within 3 postoperative years for indications ranging from wound
      breakdown to contralateral ACL rupture. While previous studies revealed high
      rates of complication after pediatric ACLR due primarily to graft failure, we
      found that re-tear is responsible for less than half of the 3-year RTOR risk. As
      almost half of re-tears in our sample occurred before clearance to return to full
      activities, we suspect that the high rate of complication is largely attributable
      to pediatric patients' high activity levels and difficulties adhering to
      postoperative restrictions. Early treatment of meniscus pathology may reduce
      rates of RTOR. LEVEL OF EVIDENCE: Level III-therapeutic.

PMID- 29189475
TI  - Responding to Financial Challenges by Reducing Costs and Improving Quality.

PMID- 29189476
TI  - Pursuit of Value Drives Strategy to Improve Operations and Outcomes.
AB  - The future of American healthcare remains cloudy, with the shifting contours of
      regulatory and fiscal reform still being shaped. Providers are beset by many
      challenges that vary but often include state and federal healthcare funding
      decisions that are antithetical to the interests of patients and aging
      populations. Regional public health crises and rapidly evolving relationships
      with third-party payers complicate matters even further.Yale New Haven Health
      System decided to pursue value as its overriding strategy for navigating the
      uncertainty in healthcare that is likely to persist for years to come. Many, if
      not most, of the challenges we face at Yale New Haven Health are shared by health
      systems across the country; the operational concepts that drive our strategy
      likely will be familiar. The differentiator is the execution: At Yale New Haven
      Health, infusing our organization with a culture of high reliability, as well as
      adopting the practice of clinical redesign, has yielded concrete enhancements in
      patient care, operational resilience, and financial sustainability. Clinical
      redesign saved Yale New Haven Health nearly $25 million in direct costs in one
      year alone.

PMID- 29189477
TI  - Remaining Financially Viable in a Time of Healthcare Transition.
AB  - In an unstable healthcare environment, Western Maryland Health System has been
      demonstrating stability. We have responded to the many challenges that hospitals
      face and managed to thrive in the new, value-based world.We made the transition
      to value-based payment and care delivery models through innovations in Maryland's
      payment system. In 2010, we recognized that becoming a demonstration project for
      value-based care would benefit our health system as we dealt with an aging and
      shrinking regional population. By moving care away from the acute setting to
      other settings across the care continuum, we now treat patients in the most
      appropriate setting (e.g., the home, physician office, clinic, and even senior
      centers, churches, and homeless shelters).As we have transitioned care, we have
      also transitioned our workforce. With fewer acute care patients, we need fewer
      staff members at the bedside. Many of our staff have shifted to delivering care
      in pre- and post-acute care settings.To improve our financial performance, we
      formed an alliance of three health systems. This new alliance has found increased
      savings by consolidating services, managing regionwide population health
      initiatives, and benchmarking clinical quality through best practices. Through
      the alliance, each individual health system is stronger and well augmented by the
      savings that it could not achieve separately.The transition has not been easy,
      but we have shown that it is achievable. We have identified a number of solutions
      to reduce costs and generate savings while enhancing quality and patient safety.
      These solutions may present a pathway to success for other organizations seeking
      to move to value-based care delivery and new payment models.

PMID- 29189478
TI  - Performance Improvement and Financial Transition Start with Culture.

PMID- 29189479
TI  - The Pursuit of Value for Financial Viability.

PMID- 29189480
TI  - Value Strategies in Action: Two Case Studies.

PMID- 29189481
TI  - Incidental Cardiac Findings in Non-Electrocardiogram-gated Thoracic Computed
      Tomography of Intensive Care Unit Patients: Assessment of Prevalence and
      Underreporting.
AB  - PURPOSE: Cardiac findings frequently remain unreported on non-electrocardiogram
      (ECG)-gated computed tomography (CT). Although the clinical relevance of such
      findings may be limited in a general patient population, they may have
      significant impact in intensive care patients. Thus, the purpose of this study
      was to evaluate the prevalence, underreporting, and clinical relevance of
      incidental cardiac findings in intensive care unit (ICU) patients. MATERIALS AND
      METHODS: Non-ECG-gated chest CT examinations of ICU patients were retrospectively
      analyzed for incidental cardiac findings. The findings were classified into 3
      categories (A to C): category A findings, which carry potential for risk to life;
      category B findings, which have a potential for significant morbidity; category C
      findings, which have a possible effect on prognosis. RESULTS: A total of 500
      patients who underwent non-ECG-gated thoracic CT examinations were included. Of
      the 500 patients, 403 presented with 1443 cardiac findings. Of all cardiac
      findings, 37% were described in the initial written report. Sixty category A
      findings were detected, of which 48% were not mentioned in the report. Six
      hundred forty category B findings were detected, of which 77% were not described
      in the report. The remaining 743 findings were classified as category C, 55% of
      which were not reported in the report. CONCLUSIONS: The prevalence as well as the
      rate of underreporting of incidental cardiac findings in non-ECG-gated chest CT
      of ICU patients is very high. The results of this study underscore the importance
      of dedicated training for assessment of cardiac structures and conditions, which
      may be detected on non-ECG-gated chest CT.

PMID- 29189482
TI  - Analysis of Biomarkers Within the Initial 2 Years Posttransplant and 5-Year
      Kidney Transplant Outcomes: Results From Clinical Trials in Organ Transplantation
      17.
AB  - BACKGROUND: An early posttransplant biomarker/surrogate marker for kidney
      allograft loss has the potential to guide targeted interventions. Previously
      published findings, including results from the Clinical Trials in Organ
      Transplantation (CTOT)-01 study, showed that elevated urinary chemokine CXCL9
      levels and elevated frequencies of donor-reactive interferon gamma (IFNgamma)
      producing T cells by enzyme-linked immunosorbent spot (ELISPOT) assay associated
      with acute cellular rejection within the first year and with lower 1-year
      posttransplant estimated glomerular filtration rate (eGFR). How well these
      biomarkers correlate with late outcomes, including graft loss, is unclear.
      METHODS: In CTOT-17, we obtained 5-year outcomes in the CTOT-01 cohort and
      correlated them with (a) biomarker results and (b) changes in eGFR (Chronic
      Kidney Disease Epidemiology Collaboration formula) over the initial 2 years
      posttransplant using univariable analysis and multivariable logistic regression.
      RESULTS: Graft loss occurred in 14 (7.6%) of 184 subjects 2 to 5 years
      posttransplant. Neither IFNgamma ELISPOTs nor urinary CXCL9 were informative. In
      contrast, a 40% or greater decline in eGFR from 6 months to 2 years
      posttransplant independently correlated with 13-fold odds of 5-year graft loss
      (adjusted odds ratio, 13.1; 95% confidence interval, 3.0-56.6), a result that was
      validated in the independent Genomics of Chronic Allograft Rejection cohort (n =
      165; adjusted odds ratio, 11.2). CONCLUSIONS: We conclude that although
      pretransplant and early posttransplant ELISPOT and chemokine measurements
      associate with outcomes within 2 years posttransplant, changes in eGFR between 3
      or 6 months and 24 months are better surrogates for 5-year outcomes, including
      graft loss.

PMID- 29189483
TI  - Heme Oxygenase 1 Attenuates Hypoxia-Reoxygenation Injury in Mice Liver Sinusoidal
      Endothelial Cells.
AB  - BACKGROUND: Heme oxygenase 1 (HO-1), a heat shock protein, can be involved in the
      resolution of inflammation by modulating cytokine expression and apoptotic cell
      death. Based on recent evidence that liver sinusoidal endothelial cells (LSECs)
      is the critical target in early period of liver ischemia-reperfusion injury
      (IRI), this study aims to clarify whether overexpression of HO-1 gene provides a
      protective effect on mice LSECs. METHODS: LSECs were transfected with adenovirus
      vectors encoding mice HO-1 gene (Ad-HO-1) or green fluorescent protein. Controls
      were not infected with any vector. LSECs were then treated with hypoxic or
      normoxic culture. We used low serum culture medium and hypoxia-reoxygenation (H
      R) conditions to cause IRI in vitro. The transfection efficiency of HO-1 gene in
      LSECs, after 48 hours of transfection, and the effect of HO-1 on the model of H-R
      injury in LSECs were observed. RESULTS: Transfection of LSECs with Ad-HO-1 was at
      an optimal dose (multiplicity of infection = 80) to markedly express HO-1 mRNA
      and protein. Groups of overexpressed HO-1 showed lower levels of inflammatory
      factor mediators IL-6 and TNF-alpha. Survival rate of the cells after H-R injury
      was higher and attributed to overexpressed HO-1. In contrast, the control
      adenovirus expressing the enhanced green fluorescent protein failed to induce HO
      1 expression and stimulated cell apoptosis. HO-1 expression was downregulated in
      all H-R groups compared with normoxia groups, which may be related to the
      disruption of the LSEC structure. CONCLUSIONS: Upregulation of HO-1 can attenuate
      H-R injury in LSECs by inhibiting proinflammatory cytokine release and
      diminishing apoptotic cell death.

PMID- 29189484
TI  - Comparison of BQ123, Epoprostenol, and Verapamil as Vasodilators During
      Normothermic Ex Vivo Liver Machine Perfusion.
AB  - BACKGROUND: The optimal vasodilator to avoid hepatic artery vasospasm during
      normothermic ex vivo liver perfusion (NEVLP) is yet to be determined. We compared
      safety and efficacy of BQ123 (endothelin1 antagonist), epoprostenol (prostacyclin
      analogue), and verapamil (calcium channel antagonist). METHODS: Livers from
      porcine heart beating donors were perfused for 3 hours and transplanted into
      recipient pigs. Four groups were compared: group 1, livers perfused with a dose
      of 1.25 mg of BQ123 at baseline and at 2 hours of perfusion; group 2,
      epoprostenol at a continuous infusion of 4 mg/h; group 3, verapamil 2.5 mg at
      baseline and at 2 hours of perfusion; group 4, no vasodilator used during ex vivo
      perfusion. Liver injury and function were assessed during perfusion, and daily
      posttransplantation until postoperative day (POD) 3. All groups were compared
      with a cold storage group for postoperative graft function. RESULTS: Hepatic
      artery flow during NEVLP was significantly higher in BQ123 compared with
      verapamil, epoprostenol, and no vasodilator-treated livers. Aspartate
      aminotransferase levels were significantly lower with BQ123 and verapamil
      compared with epoprostenol and control group during perfusion. Peak aspartate
      aminotransferase levels were lower in pigs receiving BQ123 and verapamil perfused
      grafts compared with epoprostenol and control group. International Normalized
      Ratio, alkaline phosphatase, and total bilirubin levels were lower in the BQ123
      and verapamil groups compared to epoprostenol group. Cold storage group had
      increased markers of ischemia reperfusion injury and slower graft function
      recovery compared to machine perfused grafts. CONCLUSION: The use of BQ123,
      epoprostenol, and verapamil during NEVLP is safe. Livers perfused with BQ123 and
      verapamil have higher hepatic artery flow and reduced hepatocyte injury during
      perfusion compared with epoprostenol. Hepatic artery flow is significantly
      reduced in the absence of vasodilators during NEVLP.

PMID- 29189485
TI  - Myeloid-Derived Suppressor Cells and Their Potential Application in
      Transplantation.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of
      immunosuppressive cells of the myeloid lineage upregulated by mediators of
      inflammation, such as IL-2, granulocyte colony-stimulating factor, and S100A8/A9.
      These cells have been studied extensively by tumor biologists. Because of their
      robust immunosuppressive potential, MDSCs have stirred recent interest among
      transplant immunologists as well. MDSCs inhibit T-cell responses through, among
      other mechanisms, the activity of arginase-1 and inducible nitric oxide synthase,
      and the expansion of T regulatory cells. In the context of transplantation, MDSCs
      have been studied in several animal models, and to a lesser degree in humans.
      Here, we will review the immunosuppressive qualities of this important cell type
      and discuss the relevant studies of MDSCs in transplantation. It may be possible
      to exploit the immunosuppressive capacity of MDSCs for the benefit of transplant
      patients.

PMID- 29189486
TI  - Association of Cardiac Abnormalities to the Frail Phenotype in Cirrhotic Patients
      on the Waitlist: From the Functional Assessment in Liver Transplantation Study.
AB  - BACKGROUND: Frailty is a syndrome of decreased physiologic reserve that results
      from compromise of multiple physiologic systems including cardiovascular system.
      We aimed to determine the association between the frail phenotype and cardiac
      abnormalities in liver transplant (LT) candidates through evaluation of
      transthoracic echocardiography (TTE) indices. METHODS: Included were consecutive
      outpatients listed for LT who underwent a frailty assessment from January 1,
      2014, to June 30, 2016 (using the Liver Frailty Index) and a 2
      dimensional/Doppler TTE examination. Patients were categorized as robust,
      intermediate frail, or frail by the Liver Frailty Index based on scores of less
      than 3.2, between 3.2 and 4.5, or 4.5 or greater. Linear regression assessed
      associations between the Liver Frailty Index and TTE indices. RESULTS: Of 335
      patients, 19% were robust, 65% intermediate frail, and 16% frail. TTE indices of
      left atrial (LA) dilatation differed significantly by frailty status: median LA
      dimension (P = 0.03), LA volume index (LAVI mL/m; P < 0.001) and %LAVI > 34 mL/m
      (P = 0.001). In linear regression adjusted for age, sex, hypertension, and
      diabetes, the Liver Frailty Index was positively associated with LA dimension
      (coeff, 0.20; 95% confidence interval [CI], 0.07-0.34), LAVI mL/m (coeff, 0.01;
      95% CI, 0.005-0.02), ejection fraction (coeff, 1.59; 95% CI, 0.32-2.85), and
      pulmonary artery systolic pressure (coeff, 0.01; 95% CI, 0.003-0.02), and
      negatively associated with LV hypertrophy (coeff, -0.22; 95% CI, -0.37 to -0.06).
      CONCLUSIONS: In LT candidates, frailty is associated with cardiac structural and
      functional changes, independent of known risk factors. Our study provides
      evidence to support that measures of frailty in cirrhotic patients encompass
      abnormalities of the cardiovascular system and may inform assessments of
      cardiovascular reserve in this population.

PMID- 29189488
TI  - Interim 18F-FDG PET/CT and BCL2 for predicting the prognosis of patients with
      diffuse large B-cell lymphoma in the rituximab era.
AB  - OBJECTIVE: In this study, we investigated the prognostic role of interim fluorine
      18-fluorodeoxyglucose PET/computed tomography (I-PET/CT) and BCL2 in diffuse
      large B-cell lymphoma (DLBCL) patients treated with rituximab-containing
      chemotherapy. MATERIALS AND METHODS: A total of 106 patients with newly diagnosed
      DLBCL underwent PET/CT scans at baseline and a subsequent I-PET/CT after the
      fourth cycle of chemotherapy. I-PET/CT was analyzed using the Deauville five
      point score. The prognostic significance of I-PET/CT and BCL2 was evaluated by
      predicting progression-free survival (PFS) and overall survival (OS). RESULTS:
      With a median follow-up of 25 months, the 2-year PFS and OS were 78 and 95% in
      the I-PET/CT-negative group and 33 and 57% in the I-PET/CT-positive group
      (P<0.001). Patients with BCL2 positivity showed a shorter PFS than the BCL2
      negative patients (P=0.002), but not in OS (P=0.068). In multivariate analysis, I
      PET/CT and BCL2 were independent variables in assessing the outcome of PFS. I
      PET/CT was also an independent factor for OS. Irrespective of the results of
      BCL2, patients with I-PET/CT positivity had a significant inferior outcome than
      the I-PET/CT-negative patients. In the I-PET/CT-negative group, patients with
      BCL2 positivity had a significantly shorter PFS than the BCL2-negative patients
      (P=0.005). CONCLUSION: I-PET/CT and BCL2 were two significant independent
      indicators of outcome for patients with DLBCL in the rituximab era. I-PET/CT was
      much better than BCL2 for patient stratification. BCL2 showed its supplementary
      role for further patient stratification when I-PET/CT was negative.

PMID- 29189487
TI  - Rituximab and Therapeutic Plasma Exchange in Recurrent Focal Segmental
      Glomerulosclerosis Postkidney Transplantation.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of end
      stage renal disease with a high rate of recurrence after kidney transplantation.
      Several factors, such as white race, rapid progression, and previous allograft
      failure due to recurrence, were found to be risks of recurrence. Data are limited
      on the benefits of rituximab and/or therapeutic plasma exchange (TPE) in
      preventing recurrence. In this study, we sought to assess the efficacy of
      rituximab and TPE for the prevention and treatment of recurrent FSGS after kidney
      transplantation. METHODS: We enrolled 66 patients with FSGS in this prospective
      observational study and followed their outcomes. Patients with high risk for
      recurrence received preventative therapy with TPE and/or rituximab. RESULTS:
      Twenty-three (62%) of the 37 patients who received preventative therapy developed
      recurrence compared with 14 (51%) recurrences of the 27 patients who did not
      receive any therapy (P = 0.21). There was a trend for less relapse when rituximab
      was used as a therapy for recurrent FSGS (6/22 vs 9/18, P = 0.066). We used a
      clinical score of 5 values to assess the prediction of FSGS recurrence. A score
      of 3 or more had a predictive receiver operating characteristic curve of 0.72.
      Treatment with TPE and/or rituximab resulted in better allograft survival than
      historical studies. Allograft failure because of recurrent FSGS occurred in only
      6 (9%) patients. CONCLUSIONS: Preventative therapies do not decrease the
      recurrence rate of recurrent FSGS. However, prompt treatment of recurrence with
      these therapies may result in improved outcomes.

PMID- 29189489
TI  - Utility of whole-body (head-to-toe) PET/CT in the evaluation of melanoma and
      sarcoma patients.
AB  - OBJECTIVE: The aim of this study was to assess the added benefit of whole-body
      (head-to-toes) PET/CT versus routine 'eyes-to-thighs' PET/CT of melanoma and
      sarcoma patients. PATIENTS AND METHODS: We performed a retrospective review of
      consecutive whole-body PET/CT scans from January 2006 through December 2010 in
      patients with melanoma or sarcoma. PET abnormalities in the brain, distal thighs,
      and legs were recorded and clinical significance was assessed on the basis of
      pathology, imaging studies, and clinical follow-up. Patients with known primary
      lesions distal to the proximal femora were excluded as these patients would
      routinely undergo 'head-to-toe' PET/CT. RESULTS: We reviewed reports from 352
      PET/CT examinations in 194 patients with melanoma and 75 PET/CT examinations in
      44 patients with sarcoma. Melanoma: 13 patients had brain metastases on PET. In
      five of these patients, lesions were unknown, but all were in the setting of
      other metastatic disease. Twenty-seven patients had lower extremity metastases,
      all in the setting of other metastatic disease. No lower extremity metastases
      were found in the remaining 167 patients. Sarcoma: one patient had an isolated,
      unexpected brain metastasis. Six patients had leg metastases, but none were
      isolated. No lower extremity metastases were found in the remaining 38 patients.
      CONCLUSION: In patients with melanoma and sarcoma, inclusion of entire lower
      extremities adds little additional clinical value as detection of isolated,
      unexpected metastasis is rare. Brain imaging may add value as the presence of
      brain metastases alters clinical management. Overall, in patients with melanoma
      or sarcoma, whole-brain PET/CT imaging may be of value, but routine inclusion of
      the entire lower extremities adds little additional value.

PMID- 29189490
TI  - Excretion and whole-body retention of radium-223 dichloride administered for the
      treatment of bone metastases from castration resistant prostate cancer.
AB  - OBJECTIVE: The aim of the study was to determine the fraction of administered
      activity that was excreted and retained by a small cohort of patients who each
      received treatment with radium-223 dichloride (Ra). Ra is an alpha-emitting
      radionuclide that has been approved for use in the treatment of bone metastases
      that are secondary to castration resistant prostate cancer. PATIENTS AND METHODS:
      Six patients received two weight-based administrations of Ra 6 weeks apart.
      Activity excreted in the urine and faeces during the first 48 h following each
      treatment was assessed by direct counting of the excreta. During the same period
      the whole-body retention of Ra was also determined using a single probe counting
      system. The results of the excreta counting and the whole-body counting were
      compared to determine whether whole-body counting was a suitable surrogate for
      assessing excretion. Further whole-body retention counts were made at around 3,
      4, 7 and 42 days following treatment. RESULTS: Patterns of excretion and
      retention of Ra varied significantly between patients, but were similar for each
      patient's pair of treatments. The cumulative maximum activity excreted in the
      initial 8-h period following the Ra administration was 2.6% that increased to 39%
      at 48 h. The median excreted activity at ~1 and 6 weeks after treatment was 70
      and 86%, respectively. Skeletal retention of Ra at 6 weeks ranged from 11 to 60%
      of the administered activity.

PMID- 29189491
TI  - Project ECHO: A Telementoring Network Model for Continuing Professional
      Development.
AB  - INTRODUCTION: A major challenge with current systems of CME is the inability to
      translate the explosive growth in health care knowledge into daily practice.
      Project ECHO (Extension for Community Healthcare Outcomes) is a telementoring
      network designed for continuing professional development (CPD) and improving
      patient outcomes. The purpose of this article was to describe how the model has
      complied with recommendations from several authoritative reports about
      redesigning and enhancing CPD. METHODS: This model links primary care clinicians
      through a knowledge network with an interprofessional team of specialists from an
      academic medical center who provide telementoring and ongoing education enabling
      community clinicians to treat patients with a variety of complex conditions.
      Knowledge and skills are shared during weekly condition-specific
      videoconferences. RESULTS: The model exemplifies learning as described in the
      seven levels of CPD by Moore (participation, satisfaction, learning, competence,
      performance, patient, and community health). The model is also aligned with
      recommendations from four national reports intended to redesign knowledge
      transfer in improving health care. Efforts in learning sessions focus on
      information that is relevant to practice, focus on evidence, education
      methodology, tailoring of recommendations to individual needs and community
      resources, and interprofessionalism. DISCUSSION: Project ECHO serves as a
      telementoring network model of CPD that aligns with current best practice
      recommendations for CME. This transformative initiative has the potential to
      serve as a leading model for larger scale CPD, nationally and globally, to
      enhance access to care, improve quality, and reduce cost.

PMID- 29189492
TI  - The Prato Method: A Guide to the Application of Economic Evaluations in Health
      Professions Education Research.
AB  - The estimation of cost and value in health professions education should involve
      robust methodologies and decision tools. These methods and tools should be
      applied consistently and transparently, but more importantly, employed in the
      appropriate context depending on the availability of data, target estimates, and
      stakeholder focus. Best practice methodology and application of decision tools
      will allow for a clearer and more comprehensive understanding of the return on
      investment of health profession education interventions by shedding greater light
      on the full opportunity cost of providing programs and the value of such programs
      to learners and recipients of health care services more broadly. This article
      provides insight into the basic methods, decision tools, and key evaluation
      concepts that might be considered for the purpose of undertaking cost and value
      research in continuing education for health professionals. These methods and
      decision tools are based on consolidated discussions by the organizing delegates
      of the inaugural Symposium of the Society for Cost and Value of Health
      Professions Education, held in Prato, Italy, October 2015. In summary, the
      application of economic methods and tools used for analyzing health professions
      education is currently inconsistent. This article provides an overview and
      recommendations on the use of certain economic methods and tools when evaluating
      health profession education programs. It also provides a clear understanding of
      key evaluation concepts important for undertaking an economic review of a
      program.

PMID- 29189493
TI  - What Family Physicians Really Think of Maintenance of Certification Part II
      Activities.
AB  - INTRODUCTION: This study examines how improving curricular content and technical
      interface issues could make maintenance of certification activities more
      meaningful to American Board of Family Medicine diplomates completing Maintenance
      of Certification for Family Physicians (MC-FP) Program self-assessment modules
      (SAMs). METHODS: We used a sequential exploratory design to analyze quantitative
      and qualitative data from 320,500 surveys of family physicians who completed a
      SAM between January 2004 and April 2013. This included numeric rating scales and
      free text comments. Basic statistical rankings, template-based automated coding,
      and emergent coding were used to analyze SAM experience and identify thematic
      content. RESULTS: Across SAMs, numeric ratings were universally high and positive
      free text comments outnumbered negative comments two to one. When comparing
      feedback on the knowledge assessment and clinical simulation (CS) activities,
      SAMs were rated less favorably when the frequency of ideas identified by
      participants as most prevalent in one activity mismatched those identified as
      most prevalent in the companion activity. Participants were also critical of
      navigation issues, technical issues, and a lack of realness in the CS activity.
      DISCUSSION: Whether analyzed through quantitative data, qualitative data, or
      mixed methods, a large majority of participants rated their experience with SAMs
      highly. When individual SAMs were rated poorly, it seemed to be due to
      discordance in ideas emphasized between the knowledge assessment and CS
      components, or an opinion regarding the SAM topic that existed independent of the
      SAM process.

PMID- 29189494
TI  - Rethinking Remediation: A Model to Support the Detailed Diagnosis of Clinicians'
      Performance Problems and the Development of Effective Remediation Plans.
AB  - The successful remediation of clinicians demonstrating poor performance in the
      workplace is essential to ensure the provision of safe patient care. Clinicians
      may develop performance problems for numerous reasons, including health, personal
      factors, the workplace environment, or outdated knowledge/skills. Performance
      problems are often complex involving multifactorial issues, encompassing
      knowledge, skills, and professional behaviors. It is important that (where
      possible and appropriate) clinicians are supported through effective remediation
      to return them to safe clinical practice. A review of the literature demonstrated
      that research into remediation is in its infancy, with little known about the
      effectiveness of remediation programs currently. Current strategies for the
      development of remediation programs are mostly "intuitive"; a few draw upon
      established theories to inform their approach. Similarly, although it has been
      established that identification of the nature/scope of performance problems
      through assessment is an essential first step within remediation, the need for a
      more widespread "diagnosis" of why the problems exist is emerging. These reasons
      for poor performance, particularly in the context of experienced practicing
      clinicians, are likely to have an impact on the potential success of remediation
      and should be considered within the "diagnosis." A new model for diagnosing the
      performance problems of the clinicians has been developed, using behavioral
      change theories to explore known barriers to successful remediation, such as
      insight, motivation, attitude, self-efficacy, and the working environment, in
      addition to addressing known deficits regarding knowledge and skills. This novel
      approach is described in this article. An initial feasibility study has
      demonstrated the acceptability and practical implementation of our model.

PMID- 29189495
TI  - Lumbar Spine Anatomy in Women Sustaining Unintentional Dural Puncture During
      Labor Epidural Placement: A Descriptive Study Using Magnetic Resonance Imaging
      and Ultrasound.
AB  - BACKGROUND AND OBJECTIVES: Unintentional dural puncture is one of the most
      frequent complications of the epidural technique. One previous study suggested
      that atypical sonoanatomy of the ligamentum flavum/dura mater unit may be a risk
      factor for this complication. In this study, we describe the anatomy of the
      lumbar spine, assessed by magnetic resonance imaging (MRI) and ultrasound, in
      women sustaining unintentional dural puncture during epidural catheter placement
      for labor analgesia. METHODS: We approached women who sustained a recognized
      unintentional dural puncture. Following consent, technical aspects of the
      epidural catheter placement were documented. Postpartum MRI of the lumbar spine
      and bedside spinal ultrasound were performed. Ultrasound images of the ligamentum
      flavum/dura mater unit in the transverse view were classified as typical,
      atypical, or inconclusive. Magnetic resonance imaging images were reviewed by a
      neuroradiologist, who was blinded to the level of the puncture. RESULTS: We
      included 10 women with unintentional dural punctures in the study. In 5 of the 10
      women, these dural punctures occurred despite epidural catheter insertion by
      experienced practitioners. These women had a mean body mass index of 28.5 kg/m
      (range, 24-38 kg/m). Two women suffered dural punctures twice. Ultrasound imaging
      in the paramedian view produced typical images in all patients. In the transverse
      view, 7 of 10 women showed atypical or inconclusive images, with atypical images
      seen at either L4/5 or L5/S1. Magnetic resonance imaging results revealed no
      anatomical abnormalities, with the exception of 1 woman who showed a ligamentum
      flavum gap away from the puncture site. CONCLUSIONS: Our results suggest that
      unintentional dural punctures occur in likely anatomically normal women.
      Furthermore, the transverse ultrasound views may fail to demonstrate typical
      ligamentum flavum/dura mater unit at the lower lumbar levels despite its
      confirmed presence by MRI.

PMID- 29189496
TI  - Artificial Neural Network: A Method for Prediction of Surgery-Related Pressure
      Injury in Cardiovascular Surgical Patients.
AB  - PURPOSE: The aim of this study was to build an artificial neural network (ANN)
      model for predicting surgery-related pressure injury (SRPI) in cardiovascular
      surgical patients. DESIGN: Prospective cohort study. SUBJECTS AND SETTING: One
      hundred forty-nine patients who had cardiovascular surgery were included in the
      study. This study was conducted in a 1000-bed teaching hospital in Eastern China
      where 250 to 350 cardiac surgeries are performed each year. METHODS: We performed
      a prospective cohort study among consecutive patients undergoing cardiovascular
      surgery between January and December 2015. The ANN model was built based on
      possible SRPI risk factors. The model performance was tested by a receiver
      operating characteristic curve and the C-index. A C-index from 0.5 to 0.7 is
      classified as having low accuracy, 0.7 to 0.9 as having moderate accuracy, and
      0.9 to 1.0 as having high accuracy. We also compared the actual SRPI incidences
      based on the ANN stratification. RESULTS: Thirty-seven of 147 patients developed
      SRPIs, yielding an incidence rate of 24.8% (95% CI, 18.1-32.6). The C-index was
      0.815, which showed the ANN model had a moderate prediction value for SRPI.
      According to the ANN model, the SRPI predicting incidence ranged from 6.4% to
      67.7%. Surgery-related pressure injury incidences were significantly different
      among 3 risk groups stratified by the ANN (P < .05). CONCLUSION: We established
      an ANN model that provides moderate prediction of SRPI in patients undergoing
      cardiovascular surgical procedures. Identification and additional associated
      factors should be incorporated into the ANN model to increase its predictive
      ability.

PMID- 29189497
TI  - Catalyzing State Public Health Agency Actions to Prevent Injuries and Violence:
      Introductory Remarks.

PMID- 29189498
TI  - Introduction to the Special Issue: Catalyzing State Public Health Agency Actions
      to Prevent Injuries and Violence.

PMID- 29189499
TI  - Mind the Gap: Approaches to Addressing the Research-to-Practice, Practice-to
      Research Chasm.

PMID- 29189500
TI  - Innovative Methods for Designing Actionable Program Evaluation.
AB  - CONTEXT: For most programs, whether funded through governmental agencies or
      nongovernmental organizations, demonstrating the impact of implemented activities
      is vital to ensuring continued funding and support. OBJECTIVE: Program evaluation
      is a critical tool that serves the dual purpose of describing impact and
      identifying areas for program improvement. From a funder's perspective,
      describing the individual and collective impact of state-based programs can be
      challenging due to variations in strategies being implemented and types of data
      being collected. DESIGN: A case study was used to describe the actionable, mixed
      methods evaluation of the Core Violence and Injury Prevention Program (Core
      VIPP), including how the evaluation design and approach shifted to address
      evolving challenges faced by award recipients over time. Particular emphasis is
      given to innovative methods for collecting, analyzing, and disseminating data for
      key state and federal stakeholders. RESULTS: The results of the Core VIPP
      evaluation showed how this funding played a vital role in building injury and
      violence prevention capacity in state health departments, leading to a decrease
      in both intermediate and long-term outcomes. CONCLUSIONS: The lessons learned
      through the mixed-method evaluation of the Core VIPP informed the structure of
      the subsequent funding cycle (Core SVIPP) to include more prescriptive
      requirements for evidence-based implementation and a state support team structure
      for delivery of training and technical assistance.

PMID- 29189501
TI  - State Injury Programs' Response to the Opioid Epidemic: The Role of CDC's Core
      Violence and Injury Prevention Program.
AB  - The Centers for Disease Control and Prevention's (CDC's) Core Violence and Injury
      Prevention Program (Core) supports capacity of state violence and injury
      prevention programs to implement evidence-based interventions. Several Core
      funded states prioritized prescription drug overdose (PDO) and leveraged their
      systems to identify and respond to the epidemic before specific PDO prevention
      funding was available through CDC. This article describes activities employed by
      Core-funded states early in the epidemic. Four case examples illustrate states'
      approaches within the context of their systems and partners. While Core funding
      is not sufficient to support a comprehensive PDO prevention program, having Core
      in place at the beginning of the emerging epidemic had critical implications for
      identifying the problem and developing systems that were later expanded as
      additional resources became available. Important components included staffing
      support to bolster programmatic and epidemiological capacity; diverse and
      collaborative partnerships; and use of surveillance and evidence-informed best
      practices to prioritize decision-making.

PMID- 29189503
TI  - Indicators for Evaluating Community- and Societal-Level Risk and Protective
      Factors for Violence Prevention: Findings From a Review of the Literature.
AB  - Programs geared toward preventing violence before it occurs at the community and
      societal levels of the social ecology are particularly challenging to evaluate.
      These programs are often focused on impacting the antecedents (or risk and
      protective factors) to violence, making it difficult to determine program success
      when solely relying on measures of violence reduction. The goal of this
      literature review is to identify indicators to measure risk and protective
      factors for violence that are accessible and measured at the community level.
      Indicators of community- and societal-level risk and protective factors from 116
      articles are identified. These indicators strengthen violence prevention
      researchers' and practitioners' ability to detect proximal effects of violence
      prevention programs, practices, and policies, and provide timely feedback on the
      impact of their work. Thus, opportunities exist for violence prevention
      researchers to further study the associations between various indicators and
      different violent outcomes and to inform practitioner, evaluator, and funder
      developed logic models that include indicators of relevant risk and protective
      factors for crosscutting violence prevention measures and outcomes.

PMID- 29189504
TI  - The Use of the Data-to-Action Framework in the Evaluation of CDC's DELTA FOCUS
      Program.
AB  - The Centers for Disease Control and Prevention's (CDC's) Domestic Violence
      Prevention Enhancements and Leadership Through Alliances, Focusing on Outcomes
      for Communities United with States (DELTA FOCUS) program is a 5-year cooperative
      agreement (2013-2018) funding 10 state domestic violence coalitions and local
      coordinated community response teams to engage in primary prevention of intimate
      partner violence. Grantees' prevention strategies were often developmental and
      emergent; therefore, CDC's approach to program oversight, administration, and
      support to grantees required a flexible approach. CDC staff adopted a Data-to
      Action Framework for the DELTA FOCUS program evaluation that supported a culture
      of learning to meet dynamic and unexpected information needs. Briefly, a Data-to
      Action Framework involves the collection and use of information in real time for
      program improvement. Utilizing this framework, the DELTA FOCUS data-to-action
      process yielded important insights into CDC's ongoing technical assistance,
      improved program accountability by providing useful materials, and information
      for internal agency leadership, and helped build a learning community among
      grantees. CDC and other funders, as decision makers, can promote program
      improvements that are data-informed by incorporating internal processes
      supportive of ongoing data collection and review.

PMID- 29189502
TI  - Connecting the Dots: State Health Department Approaches to Addressing Shared Risk
      and Protective Factors Across Multiple Forms of Violence.
AB  - Violence takes many forms, including intimate partner violence, sexual violence,
      child abuse and neglect, bullying, suicidal behavior, and elder abuse and
      neglect. These forms of violence are interconnected and often share the same root
      causes. They can also co-occur together in families and communities and can
      happen at the same time or at different stages of life. Often, due to a variety
      of factors, separate, "siloed" approaches are used to address each form of
      violence. However, understanding and implementing approaches that prevent and
      address the overlapping root causes of violence (risk factors) and promote
      factors that increase the resilience of people and communities (protective
      factors) can help practitioners more effectively and efficiently use limited
      resources to prevent multiple forms of violence and save lives. This article
      presents approaches used by 2 state health departments, the Maryland Department
      of Health and Mental Hygiene and the Colorado Department of Public Health and
      Environment, to integrate a shared risk and protective factor approach into their
      violence prevention work and identifies key lessons learned that may serve to
      inform crosscutting violence prevention efforts in other states.

PMID- 29189505
TI  - Development of a Comprehensive and Interactive Tool to Inform State Violence and
      Injury Prevention Plans.
AB  - CONTEXT: The Center of Disease Control and Prevention's Core State Violence and
      Injury Prevention Program (Core SVIPP) provides an opportunity for states to
      engage with their partners to implement, evaluate, and disseminate strategies
      that lead to the reduction and prevention of injury and violence. Core SVIPP
      requires awardees to develop or update their state injury and violence plans.
      Currently, literature informing state planning efforts is limited, especially
      regarding materials related to injury and violence. Presumably, plans that are
      higher quality result in having a greater impact on preventing injury and
      violence, and literature to improve quality would benefit prevention programming.
      OBJECTIVE: (1) To create a comprehensive injury-specific index to aid in the
      development and revision of state injury and violence prevention plans, and (2)
      to assess the reliability and utility of this index. DESIGN: Through an iterative
      development process, a workgroup of subject matter experts created the Violence
      and Injury Prevention: Comprehensive Index Tool (VIP:CIT). The tool was pilot
      tested on 3 state injury and violence prevention plans and assessed for initial
      usability. Following revisions to the tool (ie, a rubric was developed to further
      delineate consistent criteria for rating; items were added and clarified), the
      same state plans were reassessed to test interrater reliability and tool utility.
      RESULTS: For the second assessment, reliability of the VIP:CIT improved,
      indicating that the rubric was a useful addition. Qualitative feedback from
      states suggested that the tool significantly helped guide plan development and
      communicate about planning processes. CONCLUSION: The final VIP:CIT is a tool
      that can help increase plan quality, decrease the research-to-practice gap, and
      increase connectivity to emerging public health paradigms. The tool provides an
      example of tailoring guidance materials to reflect academic literature, and it
      can be easily adapted to other topic areas to promote quality of strategic plans
      for numerous outcomes.

PMID- 29189506
TI  - The Power of Academic-Practitioner Collaboration to Enhance Science and Practice
      Integration: Injury and Violence Prevention Case Studies.
AB  - One of the most substantial challenges facing the field of injury and violence
      prevention is bridging the gap between scientific knowledge and its real-world
      application to achieve population-level impact. Much synergy is gained when
      academic and practice communities collaborate; however, a number of barriers
      prevent better integration of science and practice. This article presents 3
      examples of academic-practitioner collaborations, their approaches to working
      together to address injury and violence issues, and emerging indications of the
      impact on integrating research and practice. The examples fall along the spectrum
      of engagement with nonacademic partners as coinvestigators and knowledge
      producers. They also highlight the benefits of academic-community partnerships
      and the engaged scholarship model under which Centers for Disease Control and
      Prevention-funded Injury Control Research Centers operate to address the research
      to-practice and practice-to-research gap.

PMID- 29189507
TI  - Acute Myeloid Leukemia With Central Nervous System Involvement in Children:
      Experience From the French Protocol Analysis ELAM02.
AB  - Central nervous system (CNS) involvement at diagnosis of pediatric acute myeloid
      leukemia (AML) is not considered as an independent prognostic factor. This study
      describes the prognostic value of pediatric AML with CNS involvement at
      diagnosis. Pediatric patients were treated for de novo AML in the French
      multicenter trial ELAM02. Lumbar puncture was carried out in the first week, and
      the treatment was adapted to the CNS status. No patient received CNS
      radiotherapy. The patients were classified into 2 groups: CNS+ and CNS-. Of the
      438 patients, 16% (n=70) had CNS involvement at diagnosis, and 29% showed
      clinical signs. The patients with CNS disease were younger (40% were below 2 y
      old), had a higher white blood cell count (median of 45 vs. 13 G/L), and had M4
      and M5 morphologies. The complete remission rate was similar at 92.8% for CNS+
      and 88.5% for CNS-. There was no significant difference between the CNS+ and the
      CNS- group in overall survival (76% and 71%, respectively) and event-free
      survival (57% and 52%, respectively). Regarding the occurrence of first relapse,
      the CNS+ group had a higher combined relapse rate of 26.1% compared with 10% for
      the CNS- group. The results indicate that CNS involvement at diagnosis of
      pediatric AML is not an independent prognostic factor. Triple intrathecal
      chemotherapy combined with high-dose intravenous cytarabine should be the first
      line treatment for CNS disease.

PMID- 29189508
TI  - Steroid-induced Hypertension During Induction Chemotherapy for Acute
      Lymphoblastic Leukemia in US Children's Hospitals.
AB  - Childhood acute lymphoblastic leukemia achieves excellent cure rates in part due
      to induction chemotherapy including high dose corticosteroids. Hypertension (HTN)
      is a known complication of corticosteroids, but incidence and risk factors for
      steroid-induced HTN are poorly understood. We sought to describe these using a
      large pediatric health database. Of the 5578 unique patients receiving induction
      chemotherapy, 14.7% received anti-HTN medications during their initial hospital
      admission. We found that age below 1 year, obesity, secondary diabetes mellitus,
      and abnormal glucose were associated with developing steroid-induced HTN. We also
      found that ICD-9 codes had poor sensitivity for detecting treatment of HTN,
      suggesting underreporting by physicians.

PMID- 29189509
TI  - Successful Treatment of a Very Late Isolated Relapse in an Adolescent With a
      PICALM-MLLT10 Positive T-lineage Acute Lymphoblastic Leukemia.
AB  - T-lineage ALL is an aggressive disease that needs to be treated with intensive
      treatment schedules. A late relapse rarely occurs and a clear choice for second
      line treatment is on debate. We report on a young adult with a very late isolated
      extramedullary relapse of PICALM-MLLT10 positive T-ALL, successfully treated with
      a chemotherapy-based and radiotherapy-based pediatric protocol. We demonstrate
      that relapse can occur in T-ALL although a SR-MRD behavior treated with a high
      risk protocol; specific molecular diagnostic aberrations, as PICALM-MLLT10, are
      still conserved at very late relapse; a second-line treatment based on pediatric
      protocol can be effective.

PMID- 29189510
TI  - Drug Rash, Eosinophilia, Systemic Symptoms (DRESS) in a Child With Acute
      Lymphoblastic Leukemia.

PMID- 29189511
TI  - Invasive Fungal Disease in Pediatric Acute Leukemia in the Nontransplant Setting:
      8 Years' Experience From a Tertiary Care Center in North India.
AB  - BACKGROUND/AIM: The aim of this article is to study the spectrum, changing
      prevalence, and predictors for mortality of invasive fungal disease (IFD) in
      pediatric leukemia in a resource-limited setting. OBSERVATIONS: Prevalence was 7%
      (proven, 69%; probable, 16.4%; possible, 14.6%) and did not differ between acute
      lymphoblastic leukemia and acute myeloid leukemia. Lungs were frequently involved
      (46%). Aspergillus was the commonest fungus (47%). Visceral abscesses were
      frequent with candidiasis as compared with invasive molds (P=0.016). IFD resulted
      in a prolonged admission (mean, 12.6+/-2 d; P=0.014) and death (44%)
      (Aspergillus, 50%; Candida, 50%; Mucor, 34%). Diagnosis of acute myeloid leukemia
      predicted mortality (P=0.03). CONCLUSIONS: IFD was an important cause of
      treatment related mortality in pediatric leukemia (odds ratio, 8.39). Protocolled
      use of computed tomography-chest and galactomannan-assay aided diagnosis
      (P<0.05).

PMID- 29189512
TI  - The Efficacy of Oral Vitamin B12 Replacement for Nutritional Vitamin B12
      Deficiency.
AB  - Standard treatment of vitamin B12 deficiency has not been well established in
      childhood, the ideal amount of supplemental vitamin B12 is not clear. Vitamin B12
      deficiency is classically treated with intramuscular injections. In this study,
      we aimed to investigate the efficacy of oral therapy in children with vitamin B12
      deficiency. Patients with serum cobalamin concentrations <300 pg/mL aged between
      6 months to 18 years were included in this prospective study. Children were
      treated orally either with a combination of multivitamin tablet daily or vitamin
      B12 ampules. Serum specimens were obtained at the end of first and third months
      of treatment for vitamin B12 levels. A total of 79 patients were included in the
      study. The mean pretreatment vitamin B12 level increased from 182+/-47.6 pg/mL to
      482+/-318 pg/mL after 1 month of treatment in the whole cohort. Comparison of the
      pretreatment vitamin B12 levels with first and third month posttreatment values
      showed significant difference (P-value, 0.001 and 0.028, respectively). In this
      study, oral cyanocobalamin was found effective for the treatment of vitamin B12
      deficiency in children.

PMID- 29189513
TI  - Successful Nonmyeloablative Allogeneic Stem Cell Transplant in a Child With
      Emberger Syndrome and GATA2 Mutation.
AB  - Emberger syndrome with underlying guanine-adenine-thymine-adenine 2 (GATA2)
      mutation is a rare disorder and very few successful nonmyeloablative allogeneic
      hematopoietic stem cell transplants (HSCTs) have been reported. We report a case
      of Emberger syndrome with GATA2 mutation in a 9-year-old girl who presented with
      congenital sensorineural deafness, warts, lymphedema, and Myelodysplastic
      syndrome. Her sister had died of a similar illness. She underwent a
      nonmyeloablative matched related donor peripheral blood HSCT with rabbit
      antithymoglobulin (5 mg/kg), fludarabine (160 mg/m), cyclophophamide (29 mg/kg),
      and total body irradiation (2 Gray). Graft versus host disease prophylaxis
      consisted of tacrolimus and mycophenolate moefetil. She had neutrophil
      engraftment on day+15 and fully donor chimerism by day+30. She developed limited
      chronic skin graft versus host disease on tapering off immunosuppression. She is
      disease free on day+475. The review of literature showed a total of 28 patients
      with GATA2 mutation have undergone HSCT mostly nonmyeloablative and overall
      survival is 75%. Nonmyeloablatove HSCT is feasible and safe for the patients with
      GATA2 mutation.

PMID- 29189514
TI  - Somatic PTPN11 Mutation in a Child With Neuroblastoma and Protein Losing
      Enteropathy.
AB  - Neuroblastoma and protein losing enteropathy (PLE) are diagnoses commonly seen by
      oncologists and gastroenterologists, respectively. The concurrence of these 2
      entities is rare, and not well explained. We describe the sixth case of PLE in a
      child with neuroblastoma, and the first for which genetic information is
      available. Tumor DNA had a mutation in the PTPN11 gene, which has been described
      in neuroblastoma, and in Noonan syndrome-a diagnosis in which neuroblastoma and
      PLE independently have been reported. Constitutional DNA was normal. Genetic
      studies in future patients will be needed to support the link between
      neuroblastoma and PLE.

PMID- 29189516
TI  - Relationship between concomitant benzodiazepine-opioid use and adverse outcomes
      among US veterans.
AB  - Benzodiazepines and opioids are commonly used among veterans suffering from
      mental health disorders and pain conditions. The objective of this study is to
      determine whether concomitant benzodiazepine-opioid use increases the incidence
      of adverse outcomes above the baseline risk of nonacute opioid-only use. The
      dataset contained all veterans who filled at least 1 opioid prescription during
      the years 2008 to 2012. Nonacute opioid use was defined as having opioid
      prescriptions greater than or equal to 20 days within a 60-day period.
      Concomitant use was defined as having opioid and benzodiazepine prescriptions
      that overlapped for at least 7 days. Nonacute opioid-only users were matched to
      concomitant opioid-benzodiazepine users based on propensity scores. A 365-day
      observation period was used to identify adverse outcomes. The primary outcome
      examines the existence of one or more of the following outcomes: opioid-related
      accidents and overdoses, alcohol- and nonopioid drug-related accidents and
      overdoses, self-inflicted injuries, violence-related injuries, wounds/injuries
      overall, and death. A logistic propensity score adjusted regression controlling
      for propensity toward concomitant use was used to determine the association of
      concomitant use with adverse outcomes. The final matched sample consisted of
      396,141 nonacute opioid-only using veterans and 48,971 concomitant benzodiazepine
      opioid users. Receiving opioids and benzodiazepines concomitantly increased the
      risk of experiencing an adverse outcome with an odds ratio of 1.359 (95%
      confidence interval: 1.320-1.400; P < 0.0001). Among veterans receiving opioids,
      concomitant benzodiazepine use is associated with an increased risk of adverse
      outcomes when compared to the baseline risk of opioid-only using veterans.

PMID- 29189515
TI  - Surgical interventions for the treatment of painful neuroma: a comparative meta
      analysis.
AB  - A consensus on the optimal treatment of painful neuromas does not exist. Our
      objective was to identify available data and to examine the role of surgical
      technique on outcomes following surgical management of painful neuromas. In
      accordance with the PRISMA guidelines, we performed a comprehensive literature
      search to identify studies measuring the efficacy of the surgical treatment of
      painful neuromas in the extremities (excluding Morton's neuroma and compression
      neuropathies). Surgical treatments were categorized as excision-only, excision
      and transposition, excision and cap, excision and repair, or neurolysis and
      coverage. Data on the proportion of patients with a meaningful reduction in pain
      were pooled and a random-effects meta-analysis was performed. The effects of
      confounding, study quality, and publication bias were examined with stratified,
      meta-regression, and bias analysis. Fifty-four articles met the inclusion
      criteria, many with multiple treatment groups. Outcomes reporting varied
      significantly and few studies controlled for confounding. Overall, surgical
      treatment of neuroma pain was effective in 77% of patients [95% confidence
      interval: 73-81]. No significant differences were seen between surgical
      techniques. Among studies with a mean pain duration greater than 24 months, or
      median number of operations greater than 2 prior to definitive neuroma pain
      surgery, excision and transposition or neurolysis and coverage were significantly
      more likely than other operative techniques to result in a meaningful reduction
      in pain (P < 0.05). Standardization in the reporting of surgical techniques,
      outcomes, and confounding factors is needed in future studies to enable providers
      to make comparisons across disparate techniques in the surgical treatment of
      neuroma pain.

PMID- 29189517
TI  - Can early oral prolonged-release oxycodone with or without naloxone reduce the
      duration of epidural analgesia after cystectomy? A 3-arm, randomized, double
      blind, placebo-controlled trial.
AB  - Thoracic epidural analgesia (TEA) enhances recovery after bowel surgery. Early
      postoperative prolonged-release oral formulation of oxycodone or
      oxycodone/naloxone is potentially useful as a second analgesic step to reduce the
      duration of TEA. We hypothesized that oxycodone would decrease the duration of
      TEA and combined with naloxone preserve gastrointestinal function. Ninety
      patients undergoing open cystectomy and urinary diversion were enrolled in this
      randomized double-blind, three-arm, parallel-group, placebo-controlled single
      center trial between September 2015 and February 2017. Exclusion criteria were
      known allergy to oxycodone/naloxone, pulmonary diseases, hepatopathy, and
      analgesics nonnaive patients. From postoperative day 3, patients received batches
      with oxycodone, oxycodone/naloxone, or placebo every 12 hours (n = 30 in each
      arm). Reduction of the epidural drug infusion rate was attempted with the goal to
      maintain a pain intensity <3 at rest and <5 (numeric rating score) at
      mobilization during 6 hours. Primary endpoint was duration of TEA and secondary
      endpoint return of gastrointestinal function. The median duration of TEA did not
      differ between patients treated with oxycodone/naloxone (6.7 [range 3.1-10.3]
      days), oxycodone (7.0 [3.0-9.1]), or placebo (6.4 [3.1-8.4]); P = 0.88. Time to
      the first defecation was prolonged in the oxycodone group compared to the placebo
      group (difference 22.48 hours +/-8.95; P = 0.037). In the oxycodone group, we
      found 8/30 patients with ileus (27%) compared to 2/28 (7%) in the
      oxycodone/naloxone group and to 2/30 (7%) in the placebo group; (P = 0.031).
      Oxycodone, with or without naloxone, did not reduce the duration of TEA.
      Oxycodone alone led to a delayed return of bowel function, whereas the
      combination was not different from placebo.

PMID- 29189520
TI  - The Middle Ear Muscle Reflex in Rat: Developing a Biomarker of Auditory Nerve
      Degeneration.
AB  - OBJECTIVES: The long-term goal of this research is to determine whether the
      middle ear muscle reflex can be used to predict the number of healthy auditory
      nerve fibers in hearing-impaired ears. In this study, we develop a high-impedance
      source and an animal model of the middle ear muscle reflex and explore the
      influence of signal frequency and level on parameters of the reflex to determine
      an optimal signal to examine auditory nerve fiber survival. DESIGN: A high
      impedance source was developed using a hearing aid receiver attached to a 0.06
      diameter 10.5-cm length tube. The impedance probe consisted of a microphone probe
      placed near the tip of a tube coupled to a sound source. The probe was calibrated
      by inserting it into a syringe of known volumes and impedances. The reflex in the
      anesthetized rat was measured with elicitor stimuli ranging from 3 to 16 kHz
      presented at levels ranging from 35 to 100 dB SPL to one ear while the reflex was
      measured in the opposite ear containing the probe and probe stimulus. RESULTS:
      The amplitude of the reflex increased with elicitor level and was largest at 3
      kHz. The lowest threshold was approximately 54 dB SPL for the 3-kHz stimulus. The
      rate of decay of the reflex was greatest at 16 kHz followed by 10 and 3 kHz. The
      rate of decay did not change significantly with elicitor signal level for 3 and
      16 kHz, but decreased as the level of the 10-kHz elicitor increased. A negative
      feedback model accounts for the reflex decay by having the strength of feedback
      dependent on auditory nerve input. The rise time of the reflex varied with
      frequency and changed with level for the 10- and 16-kHz signals but not
      significantly for the 3-kHz signal. The latency of the reflex increased with a
      decrease in elicitor level, and the change in latency with level was largest for
      the 10-kHz stimulus. CONCLUSIONS: Because the amplitude of the reflex in rat was
      largest with an elicitor signal at 3 kHz, had the lowest threshold, and yielded
      the least amount of decay, this may be the ideal frequency to estimate auditory
      nerve survival in hearing-impaired ears.

PMID- 29189521
TI  - Digit Triplet Test Hearing Screening With Broadband and Low-Pass Filtered Noise
      in a Middle-Aged Population.
AB  - OBJECTIVES: This study investigated whether age affects Flemish Digit Triplet
      Test (DTT) scores, as well as sensitivity and specificity of the test to detect
      high-frequency hearing impairment in middle age. DESIGN: DTT performance in
      broadband and low-pass filtered noise was assessed for 21 young and 61 middle
      aged persons with normal-hearing sensitivity. Cutoff values based on their
      performance were used to evaluate sensitivity and specificity of the DTT as a
      screening tool in 145 middle-aged persons, with varying audiometric profiles.
      RESULTS: DTT performance for normal-hearing persons depended on age in both noise
      conditions. For low-pass filtered noise, the trade-off between sensitivity and
      specificity also increased when age-adjusted cutoff values were applied for
      screening in middle age. CONCLUSIONS: The Flemish DTT with broadband noise had
      high sensitivity and specificity to detect high-frequency hearing impairment in
      middle age. Similar results were obtained for low-pass filtered noise when cutoff
      values for referral were age adjusted.

PMID- 29189522
TI  - Combined Amplification and Sound Generation for Tinnitus: A Scoping Review.
AB  - OBJECTIVES: In most cases, tinnitus is accompanied by some degree of hearing
      loss. Current tinnitus management guidelines recognize the importance of
      addressing hearing difficulties, with hearing aids being a common option. Sound
      therapy is the preferred mode of audiological tinnitus management in many
      countries, including in the United Kingdom. Combination instruments provide a
      further option for those with an aidable hearing loss, as they combine
      amplification with a sound generation option. The aims of this scoping review
      were to catalog the existing body of evidence on combined amplification and sound
      generation for tinnitus and consider opportunities for further research or
      evidence synthesis. DESIGN: A scoping review is a rigorous way to identify and
      review an established body of knowledge in the field for suggestive but not
      definitive findings and gaps in current knowledge. A wide variety of databases
      were used to ensure that all relevant records within the scope of this review
      were captured, including gray literature, conference proceedings, dissertations
      and theses, and peer-reviewed articles. Data were gathered using scoping review
      methodology and consisted of the following steps: (1) identifying potentially
      relevant records; (2) selecting relevant records; (3) extracting data; and (4)
      collating, summarizing, and reporting results. RESULTS: Searches using 20
      different databases covered peer-reviewed and gray literature and returned 5959
      records. After exclusion of duplicates and works that were out of scope, 89
      records remained for further analysis. A large number of records identified
      varied considerably in methodology, applied management programs, and type of
      devices. There were significant differences in practice between different
      countries and clinics regarding candidature and fitting of combination aids,
      partly driven by the application of different management programs. CONCLUSIONS:
      Further studies on the use and effects of combined amplification and sound
      generation for tinnitus are indicated, including further efficacy studies,
      evidence synthesis, development of guidelines, and recommended procedures that
      are based on existing knowledge, expert knowledge, and clinical service
      evaluations.

PMID- 29189523
TI  - Bilateral Sacral Ala Fractures Are Strongly Associated With Lumbopelvic
      Instability.
AB  - OBJECTIVES: To quantify the incidence of lumbopelvic instability in the setting
      of unilateral and bilateral sacral fractures and assess whether the presence of
      bilateral sacral fractures on axial imaging is a useful screening test for
      lumbopelvic instability. DESIGN: Retrospective case series. SETTING: Level I
      trauma center at an academic medical center. PATIENTS/PARTICIPANTS: A hospital
      database was used to identify patients diagnosed with a sacral fracture by The
      International Classification of Diseases, Ninth Revision (ICD-9) code from 2000
      to 2014. INTERVENTION: Axial cross-sectional imaging was reviewed to confirm the
      presence of unilateral or bilateral sacral ala fractures. Sagittal
      reconstructions were scrutinized for a transverse fracture line separating the
      lumbar spine from the pelvis, which was used to define lumbopelvic instability.
      MAIN OUTCOME MEASUREMENTS: The Roy-Camille classification system was applied to
      all identified cases of lumbopelvic instability. RESULTS: One thousand five
      hundred twenty-six patients were diagnosed with sacral fractures by the ICD-9
      code. Four hundred ninety had adequate axial and sagittal cross-sectional
      imaging. Four hundred forty-three of these patients had unilateral sacral ala
      fractures, and none of these were associated with lumbopelvic instability. Forty
      seven patients had bilateral sacral ala fractures, and 41 of these (87%) had a
      transverse component indicating some degree of lumbopelvic instability. The
      presence of bilateral sacral fractures was 100% sensitive and 99% specific for
      lumbopelvic instability. Among fractures with lumbopelvic instability, 27 (66%)
      were Roy-Camille type 1, 11 (27%) were type 2, and 3 (7%) were type 3.
      CONCLUSIONS: Bilateral sacral ala fractures are strongly associated with
      lumbopelvic instability and can be used as a very sensitive and specific
      screening tool. All patients with bilateral sacral fractures on axial computed
      tomography or magnetic resonance imaging should have close assessment of the
      sagittal plane images to evaluate for this pathology. LEVEL OF EVIDENCE:
      Diagnostic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29189524
TI  - Magnitude of Soft-Tissue Defect as a Predictor of Free Flap Failures: Does Size
      Matter?
AB  - OBJECTIVES: To examine the relationship between the magnitude of soft-tissue
      defect and the risk of free-flap and limb-salvage complications/failures. DESIGN:
      Retrospective cohort. SETTING: Level I Trauma Center. PATIENTS: One hundred
      twelve patients with free tissue transfers between January 2009 and June 2015.
      INTERVENTION: A standardized approach using a consistent team of 2 orthopaedic
      microvascular surgeons was used for each free-flap reconstruction. MAIN OUTCOME
      MEASURE: Soft tissue defect size, total or partial flap failure, and unplanned
      reoperations. RESULTS: Of 112 free-flap reconstructions, 57 complications
      occurred in 43-cases (38%) including 5 total flap failures (4.5%), 7 partial flap
      failures (6%), and 8 early (7%) and 38 delayed complications (33%). There was a
      significant correlation between the large defect size (>=200 cm) and
      partial/total flap failure (n = 80, P = 0.023). There was also a significant
      correlation between large soft tissue defect size and any complication that is,
      total or partial failure and early or delayed unplanned return to the operating
      room (n = 80, P = 0.002). Of the flaps used, multivariate analysis revealed that
      latissimus flaps had higher odds for failure. CONCLUSIONS: Soft-tissue defect
      size >=200 cm can be associated with a higher rate of total or partial flap
      failure and any complication in acute trauma setting, which may be due to a
      larger zone of injury, a higher level of difficulty in achieving complete
      debridement, and a more complex microvascular dissection. Current and future
      efforts will need to continue to focus on risk stratification for limb salvage
      efforts because an accurate assessment of risk is important to the patient,
      health care provider, and the health care system in general. LEVEL OF EVIDENCE:
      Prognostic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29189525
TI  - Nail and Locking Plate for Periprosthetic Fractures.
AB  - The incidence of periprosthetic fractures have been increasing, and in patients
      with osteopenic bone, high body mass index, or a combination both, they are
      difficult to treat and pose a high risk for malunion. Previous studies have
      compared the use of locking plates and intramedullary nails, and have found that
      each has its own strengthens and drawbacks, but neither is superior in terms of
      treating periprosthetic fractures. Here, we present the technique and series of
      patients treated with a combination of a retrograde intramedullary nail and flare
      to-flare lateral locking plate without the use of allograft or autograft
      supplementation.

PMID- 29189526
TI  - Rib Cage Measurement Reproducibility Using Biplanar Stereoradiographic 3D
      Reconstructions in Adolescent Idiopathic Scoliosis.
AB  - BACKGROUND: A reproducibility study of preoperative rib cage three-dimensional
      (3D) measurements was conducted for patients with Adolescent Idiopathic Scoliosis
      (AIS). No prior reliability study has been performed for preoperative 3D
      reconstructions of the rib cage by using stereoradiography in patients with
      preoperative AIS. Our objective was to assess the reliability of rib cage 3D
      reconstructions using biplanar stereoradiography in patients with AIS before
      surgery. METHODS: This series includes 21 patients with Lenke 1 or 2 scoliosis
      (74+/-20 degrees). All patients underwent low-dose standing biplanar radiographs.
      Two operators performed reconstructions twice each. Intraoperator repeatability,
      interoperator reproducibility, and intraclass coefficients (ICC) were calculated
      and compared between groups. RESULTS: The average rib cage volume was 4.71 L
      (SD+/-0.75 L). Two SD was 0.19 L with a coefficient of variation of 4.1%; ICC was
      0.968. The thoracic index was 0.6 (SD+/-0.1). Two SD was 0.03 with a coefficient
      of variation of 4.7% and a ICC of 0.820. As for the Spinal Penetration Index
      (6.4%; SD+/-2.4), 2SD was 0.9% with a coefficient of variation of 14.3% and a ICC
      of 0.901. The 3D rib hump 2SD (average 27+/-8 degrees) was 1.4 degrees. The
      coefficient of variation and ICC were respectively 5.1% and 0.991. CONCLUSIONS:
      Three-dimensional reconstruction of the rib cage using biplanar stereoradiography
      is a reliable method to estimate preoperative thoracic parameters in patients
      with AIS. LEVEL OF EVIDENCE: Level IV-diagnostic study.

PMID- 29189527
TI  - End Vertebra Versus Apical Vertebra: Where are We More Likely to Misplace in
      Spine Deformity?
AB  - BACKGROUND DATA: Pedicle screws placement remains technically demanding. The
      thoracic curve apex is considerably difficult due to its unique morphology and
      severe rotation. In comparison the upper end vertebrae have smaller pedicles and
      limited soft tissue exposure. This study seeks to evaluate the likelihood of
      screw misplacement at the end vertebra and apex. METHODS: A retrospective review
      of preoperative and postoperative computed tomographic (CT) scans of spinal
      deformity patients who underwent posterior spinal fusion with pedicle screw
      constructs between 2004 and 2011 was performed. Pedicles located at the upper
      instrumented vertebra (UIV) and lower instrumented vertebra (LIV), and the major
      and minor apices were evaluated. Pedicle morphology was studied on preoperative
      CT and screw placement on postoperative CT. RESULTS: In total, 188 patients met
      the inclusion criteria, 172 had preoperative CT scans and 133 had postoperative
      CT scans. The UIV had a significantly lower percentage of normal pedicles (type
      A) compared with apex major, apex minor, or LIV (59.1% vs. 76.1% vs. 77.3% vs.
      98.7%; P<0.001). UIV had significantly the lowest percentage of normal normally
      placed screws compared with LIV, apex major, or apex minor (69.4% vs. 97.3% vs.
      87.6% vs. 92.1%; P<0.001). In a logistic regression adjusted for preoperative
      Cobb angles, UIV was more likely to have screws misplaced (odds ratio =7.56; 95%
      confidence interval, 4.01-14.30; P<0.001) and abnormal pedicles (odds ratio=2.81;
      95% confidence interval, 1.52-5.19; P=0.001) compared with any other location
      studied. In abnormal pedicles, 41 (39.8%) of the 103 UIV screws were misplaced,
      whereas 10 (16.4%) of the 61 apex major, apex minor, or LIV screws were misplaced
      (P=0.007). CONCLUSIONS: The UIV presents more of a risk for pedicle screw
      misplacement and abnormal morphology when compared with LIV and apical vertebra.
      We believe these findings can aid in the surgeon's preoperative and
      intraoperative management to ensure increased success in accurate and safe
      pedicle screw placement. LEVEL OF EVIDENCE: Level III.

PMID- 29189528
TI  - Incidence and Diagnostic Evaluation of Postoperative Fever in Pediatric Patients
      With Neuromuscular Disorders.
AB  - BACKGROUND: Children with neuromuscular disorders have a significant chance of
      developing scoliosis and/or hip dislocation during childhood and adolescence and
      often undergo surgical reconstruction. Because of their high rate of medical
      comorbidities, these patients are at higher risk of postoperative complications
      and are therefore often comanaged, along with orthopaedics, by pediatric medicine
      and critical care teams. Fever during the postoperative stay is a frequent
      occurrence and often prompts extensive diagnostic workup which increases the cost
      and burden on the health system but have unclear effects on the care of the
      patient. The objective of our study was to evaluate the frequency of
      postoperative fever in pediatric patients with neuromuscular disorders after
      spine and hip deformity correction surgery and evaluate the utility of the
      diagnostic tests performed for the assessment of postoperative fever. METHODS: We
      performed an IRB-approved retrospective study on patients who underwent
      corrective surgery for neuromuscular scoliosis or hip dislocation at a single
      institution. The occurrence of postoperative fever was characterized by maximum
      temperature, postoperative day (POD) of occurrence, and frequency as defined by
      either single or multiple temperature spikes. Diagnostic tests performed for the
      workup of postoperative fever were reviewed. The cost per health effect was
      estimated by dividing the total costs of diagnostic tests by the number of tests
      that changed patient care. RESULTS: In total, 108 patients (62 females and 46
      males) were identified. A total of 42 patients (38.9%) underwent posterior spinal
      fusion and 66 (61.1%) patients underwent hip surgery (pelvic osteotomy in 8
      patients, femoral osteotomy in 31 patients, and both pelvic and femoral osteotomy
      in 27 patients). The mean age at the time of surgery was 11.1 years (range, 3 to
      18 y). In total, 66 patients (61.1%) developed postoperative fever (mean
      temperature, 38.6 degrees C). The frequency of fever was in the form of multiple
      temperature spikes in 37 patients (56%) and in the form of a single spike in 29
      patients (44%). Of the 149 diagnostic tests performed for postoperative fever,
      there were a total of 16 positive tests (10.7% of total tests ordered; n=16/149)
      including 5/27 urine analysis, 4/26 urine culture, 4/28 chest x-ray, 1/1 wound
      culture, 0/1 sputum culture, urine Gram stain 0/1, tracheal aspirate culture 0/1,
      throat culture 1/1, adenovirus polymerase chain reaction (PCR) 0/5, human
      metapneumovirus PCR 0/5, parainfluenza PCR 0/5, rhinovirus PCR 0/1, 1/3
      bronchoalveolar culture, and 0/7 respiratory virus panel. A total of 37 blood
      cultures were drawn and all were negative. There was a significant difference
      (P=0.04) in frequency of negative diagnostic workup performed at the first,
      second, and third POD as compared with positive diagnostic workup. Total cost of
      the diagnostic tests was $65,284 and the cost per health effect was $6582
      ($65,284/10). Diagnostic tests in patients with postoperative fever were
      associated with prolonged length of hospital stay in comparison with patients who
      did not perform any diagnostic workup using the Spearman rho test (P=0.02).
      CONCLUSION: In total, 61% of pediatric patients developed postoperative fever
      after surgical correction of neuromuscular deformity. An infectious source of
      postoperative fever was identified in 32.4% of patients with postoperative fever
      who underwent diagnostic workup. Urinary tract infection was the most common
      finding in patients with postoperative fever. Poor association between the
      development of postoperative fever and wound infection was found. Only 10.7% of
      fever diagnostic workup tests were positive in our population. The diagnostic
      workup tests might be less valuable if performed early on the first, second, and
      third PODs than those performed late after the third POD with exceptions based on
      clinical assessment. No patients with postoperative fever had positive blood
      cultures, therefore the routine use of blood cultures in the evaluation of
      postoperative fever in such population is not recommended. LEVEL OF EVIDENCE:
      Level IV-retrospective.

PMID- 29189529
TI  - Trends in Management and Complications of Anterior Cruciate Ligament Injuries in
      Pediatric Patients: A Survey of the PRiSM Society.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injuries have been recognized and
      treated with increasing frequency in children and adolescents. ACL reconstruction
      (ACLR) in skeletally immature patients has unique considerations and there is a
      large practice variation in the management of these injuries. The purpose of this
      study was to survey the members of the Pediatric Research in Sports Medicine
      (PRiSM) Society regarding their experience with the management and complications
      of pediatric ACL injuries. METHODS: A 15-question survey was distributed to 71
      orthopaedic members of the Pediatric Research in Sports Medicine study group.
      RESULTS: Regarding treatment of an 8-year-old child with a complete ACL tear, 53%
      of respondents recommended iliotibial band reconstruction, 33% recommended all
      epiphyseal reconstruction, and only 3% would treat nonoperatively in a brace. In
      adolescent patients with 2 years of growth remaining, 47% of respondents
      recommended a physeal "respecting" technique, 31% recommended a physeal-sparing
      technique, and 19% would perform an adult-style ACLR. There were 29 new cases of
      growth arrest reported. CONCLUSIONS: This study demonstrates that there have been
      major changes in the trends in pediatric ACLR over the past 15 years, and the
      most treatment variability is found among adolescent patients with about 2 years
      of growth remaining. The study also demonstrates that while the overall incidence
      of growth disturbance after ACLR remains low, new cases of growth disturbance
      continue to be identified. LEVEL OF EVIDENCE: Level V-survey of expert opinion
      and experience.

PMID- 29189530
TI  - Outcomes of Hip Arthroscopy in Adolescents: A Comparison of Acute Versus Chronic
      Presentation. Two-Year Minimum Follow-up.
AB  - BACKGROUND: Hip arthroscopy has been shown to be effective in managing various
      hip pathologies, including labral tears in adolescent patients. The purpose of
      this study was to ascertain whether outcomes of hip arthroscopy in patients under
      the age of 18 treated for labral tears differ depending on whether the
      presentation was acute or chronic. We also present the outcomes of the largest
      prospectively collected study on hip arthroscopy performed for labral tears in
      adolescents. METHODS: Patient reported outcome scores (PROs) for 194 patients
      undergoing hip arthroscopy for hip pathology, who were 18 or under at the time of
      surgery were prospectively collected and retrospectively reviewed. Modified
      Harris hip score (mHHS), Nonarthritic hip score (NAHS), Hip Outcome score-sport
      specific scale (HOS-SSS) and Visual Analogue Score (VAS) were the PROs collected.
      The overall cohort was assessed for outcome and a comparison was made between
      those patients who presented with acute onset of symptoms versus those who
      presented with insidious onset. RESULTS: There was significant improvement in all
      the PROs for the overall cohort, with improvement maintained over an average of
      38.5 months. There was no significant difference in outcome scores, between the
      acute and chronic groups except for change in VAS. Preoperative scores in the
      acute group were significantly lower, while postoperative scores did not differ.
      A trend toward more improvement was noted for the acute group. Overall need for
      revision surgery was 12%, with a higher rate of revision in the acute group.
      CONCLUSIONS: Hip arthroscopy in adolescent patients being treated for intra
      articular pathology is a safe procedure with favorable outcomes at minimum 2-year
      follow-up, with no significant difference in final outcomes between patients with
      acute onset of symptoms as opposed to those with more a more chronic
      presentation. Reoperation rate may be higher in patients with an acute onset.
      LEVEL OF EVIDENCE: Level II.

PMID- 29189531
TI  - Characterization of American Football Injuries in Children and Adolescents.
AB  - BACKGROUND: As a collision sport, football carries a significant risk of injury,
      as indicated by the large number of pediatric football-related injuries seen in
      emergency departments. There is little information in the medical literature
      focusing on the age-related injury patterns of this sport. Our purpose was to
      evaluate the types of football-related injuries that occur in children and
      adolescents and assess which patient characteristics, if any, affect injury
      pattern. METHODS: Retrospective chart review was performed of football-related
      injuries treated at a level 1 pediatric referral hospital emergency department
      and surrounding urgent care clinics between January 2010 and January 2014.
      Patients with e-codes for tackle football selected from the electronic medical
      record were divided into 4 age groups: younger than 8 years old, 8 to 11, 12 to
      14, and 15 to 18 years. Data collected included diagnosis codes, procedure codes,
      and hospital admission status. RESULTS: Review identified 1494 patients with 1664
      football-related injuries, including 596 appendicular skeleton fractures, 310
      sprains, 335 contusions, 170 closed head injuries, 62 dislocations, 9 spinal cord
      injuries, and 14 solid organ injuries. There were 646 (43.2%) athletes with upper
      extremity injuries and 487 (32.6%) with injuries to the lower extremity. Hospital
      admissions were required in 109 (7.3%) patients. Fracture was the most common
      injury in all four patient age groups, but occurred at a lower rate in the 15 to
      18 years old age group. The rate of soft tissue injury was higher in the 15 to 18
      years old age group. The rate of closed head injury, which included concussions,
      was highest in the younger than 8 years old age group. CONCLUSIONS: Age does
      influence the rates of certain football-related injuries in children and
      adolescents. Fractures decrease with increasing age, while the rate of soft
      tissue trauma increases with increasing age. Younger patients (younger than 8 y
      old) trended toward higher rates of closed head injury compared with other age
      groups. Awareness of these variations in injury patterns based on age could
      result in age-specific changes in equipment, training, and safety rules. LEVEL OF
      EVIDENCE: Level IV-case series.

PMID- 29189532
TI  - Pediatric Supracondylar Humerus Fractures: AAOS Appropriate Use Criteria Versus
      Actual Management at a Pediatric Level 1 Trauma Center.
AB  - OBJECTIVES: The purpose of this study was to characterize management of
      supracondylar humerus fractures (SCHFs) at a level 1 trauma center and identify
      factors contributing to divergence in management from American Academy of
      Orthopedic Surgeons (AAOS) the Appropriate Use Criteria (AUC) recommendations.
      METHODS: A query revealed 556 patients with diagnoses of SCHF between 2013 and
      2015 at a pediatric level 1 trauma center. Patients were excluded if they were
      younger than 2 years of age, older than 12 years of age, were polytrauma
      patients, or if there was not sufficient clinical or radiographic documentation,
      resulting in 449 patients. Urgent/emergent intervention was defined as surgery
      within 8 hours of presentation. Binomial logistic regression assessed whether
      various factors predicted operative versus nonoperative management. RESULTS:
      Operative management was undertaken in 0/208 (0%) type I fractures, 61/106
      (57.0%) type II fractures, and 135/135 (100%) type III fractures. Comparison with
      AUC recommendations revealed disagreement in 31% (138/449) of cases. Among 449
      patients, 44 were treated nonoperatively despite AUC recommendations for
      operative treatment. All 44 of these patients were type II SCHFs managed
      nonoperatively. There were no definitive cases of malalignment or loss of
      alignment in these nonoperative cases. Factors predictive of operative management
      were anterior humeral line not intersecting the capitellum (odds ratio, 200;
      P<0.001) and increasing age (odds ratio, 1.53; P=0.024). The AUC more frequently
      recommended urgent/emergent operative intervention (148/449, 33.0%) than was
      performed at our pediatric level 1 trauma center (50/449, 11.1%). The majority of
      this disagreement (94/98, 95.9%) consisted of uncomplicated type III SCHF treated
      operatively in >8 hours. None of these patients developed compartment syndrome or
      required an open reduction. CONCLUSIONS: The American Academy of Orthopedic
      Surgeons AUC recommended operative and urgent/emergent intervention more
      frequently than was performed at a level 1 pediatric trauma center. Patient age
      and alignment of the anterior humeral line with the capitellum, though not
      specifically addressed in the AUC, were most predictive of operative versus
      nonoperative management at our institution.

PMID- 29189533
TI  - Experimental Induction of Physeal Injuries by Fracture, Drill, and Ablation
      Techniques: Analyses of Immunohistochemical Findings.
AB  - BACKGROUND: Although physeal fractures and physeal bars can result in significant
      clinical consequences to growth and development of the injured physis, little
      orthopaedic research has focused upon this topic. Our objective was to extend a
      previously developed rat model to examine the immunohistochemical features
      following surgical application of techniques disrupting the physis. METHODS:
      Physes were surgically disrupted using fracture (control), epiphyseal scrape
      (ES), or epiphyseal drill (ED). After 1, 3, 6, 10, or 21 days, animals were
      euthanized, sites processed for histology and immunohistochemical localization of
      vascular endothelial growth factor (VEGF), Factor VIII, Sox-9, PTHrP (parathyroid
      hormone-related protein) and PTHrP-R (parathyroid hormone-related protein
      receptor) in resting, proliferative, and hypertrophic physeal zones. Incidence of
      physeal bars, vertical septa and islands within the metaphysis was quantified.
      Semiquantitative analysis of immunohistochemistry was performed. RESULTS: Physeal
      bars, vertical septa, and displaced cartilage islands were present each of the
      surgical treatments. Fisher's exact test showed a statistically significant
      increase in the presence of physeal bars (P=0.002) and vertical septa (P=0.012)
      in the ED group at 10 and 21 days. Analysis of VEGF showed significant
      differences among the surgical treatments involving the resting zone, and the
      proliferative zone for days 1, 6, and 21 (P<=0.02) with greater mean scores
      present in the fracture (control) group, followed by the ED group; the lowest
      scores were present in the ES group. PTHrP-R immunolocalization showed
      significant differences among treatments in the hypertrophic zone at days 6 and
      21 (P=0.022 and 0.044, respectively). CONCLUSIONS: On the basis of the type of
      surgical treatment, results show significant differences in the presence of VEGF
      (reflecting the vascular bed) in the resting and proliferating zones at days 1,
      6, and 21. VEGF localization was less abundant in the ED group (which had more
      physeal bars), suggesting that lack of vascular ingrowth plays a role in physeal
      bar formation. CLINICAL RELEVANCE: Basic science data presented here provide
      insight into the importance of the various regions of the physis and its repair
      and continued growth after physeal fracture. We suggest that a better
      understanding of the cellular basis of physeal arrest following physeal fracture
      may have future relevance for the development of treatments to prevent or correct
      arrest.

PMID- 29189534
TI  - Pediatric Orthopaedic Surgeons Dissatisfied in On-Call Practices Despite
      Improving Call Conditions. The 2015 POSNA Membership Survey Regarding Trauma
      Care.
AB  - BACKGROUND: To examine the current trends in trauma call coverage of pediatric
      orthopaedic surgeons in North America and to identify predictors of surgeon on
      call satisfaction. METHODS: In 2015, ~1200 active members of the Pediatric
      Orthopaedic Society of North America (POSNA) were surveyed regarding emergency
      room on-call practices. In total, 410 members completed the survey with a
      response rate of 35%. Information collected included call frequency, practice
      setting and satisfaction with call. This information was analyzed and compared
      with the 2006 and 2010 trauma call surveys of Pediatric Orthopaedic Society of
      North America membership using 2 sample difference in proportion, chi tests for
      trend and the Fisher exact tests. Logistic regression analyses were used to
      identify predictors of call satisfaction among pediatric orthopaedic surgeons.
      RESULTS: In total, 47% of pediatric orthopaedic surgeons had access to a
      designated trauma operating room in 2015, up from 39% in 2010 and 24% in 2006. In
      total, 43% of pediatric orthopaedic surgeons currently receive a stipend for
      taking call, up from 35% in 2010 and 28% in 2006. Although 83% of pediatric
      orthopaedic surgeons believe that trauma call is an integral part of their
      practice, only 53% are satisfied with their call experience. Controlling for
      covariates, believing that call is integral to one's practice doubles odds of
      call satisfaction. Having resident or fellow support and being financially
      compensated for orthopaedic trauma call also increases one's odds of
      satisfaction. The odds of being satisfied with call decrease by 7% for each year
      of increase in age of the surgeon. CONCLUSIONS: Access to a designated trauma
      operating room and financial compensation for call coverage have steadily
      increased over the past decade. A sizable majority of respondents continue to
      believe that trauma care is an integral part of being a pediatric orthopedist.
      Despite this, 47% of respondents remain dissatisfied with their trauma call
      arrangements. The age and attitude of the individual surgeon and extent of
      hospital support predict satisfaction of surgeons providing trauma coverage.
      LEVEL OF EVIDENCE: Level V-economic and decision analysis.

PMID- 29189535
TI  - Torsional Growth Modulation of Long Bones by Oblique Plating in a Rabbit Model.
AB  - BACKGROUND: There is evidence that oblique tension band plating can affect
      torsional growth in long bones. This study sought to determine if the torsional
      growth could be modulated based on the angles of the tension band plating and
      whether or not oblique plating affected overall longitudinal growth. METHODS: New
      Zealand White rabbits (10.5 wk old) had one screw placed on the metaphyseal side
      and one on the epiphyseal side of both medial and lateral sides of the right knee
      distal femoral physis. The sham group (n=5) included screw placement only. For
      the plate group (n=13), unlocked plates, angled from 0 to 76 degrees, connected
      the screws and spanned the physis. Radiographs were taken at biweekly intervals.
      After 6 weeks of growth, hindlimbs were harvested and microCT scans performed.
      Femoral length, distances between screw heads and angle between the plates were
      measured on radiographs. Femoral length differences were compared between groups.
      Femoral version was measured from 3D microCT. Plate angle changes were correlated
      to the difference in femoral version between limbs using Pearson correlation
      (significance was set to P<0.05 for all comparisons). RESULTS: Femur length
      difference between the contralateral and the operative side was significantly
      greater in the plate group compared with the sham group over time (P=0.049).
      Medial and lateral screw distances changed significantly more in the sham group
      than the plate group on both sides (P<0.001). A greater initial angle between
      plates resulted in a greater change in the angle between plates (P<0.001).
      Significant correlations were found between right-left side femoral version
      differences and initial plate angle (P=0.003) and plate angle change (P=0.014).
      CONCLUSIONS: The torsional effect of oblique plating seems to correlate with the
      amount of initial plate angle, with an additional, not negligible, longitudinal
      growth effect. CLINICAL SIGNIFICANCE: Placing plates at given angles across open
      physes may result in predictable changes in bone torsion allowing for a safer and
      less invasive option when treating childhood torsional deformities, but the
      resulting shortening of the ipsilateral femur must be considered.

PMID- 29189536
TI  - Incidence of Fractures From Perioperative Blood Pressure Cuff Use, Tourniquet
      Use, and Patient Positioning in Osteogenesis Imperfecta.
AB  - BACKGROUND: Osteogenesis imperfecta (OI) is a rare connective tissue disease with
      varying severity. Patients with OI are highly susceptible to skeletal fractures.
      Optimal perioperative management of these patients is not well defined. We
      investigated the risks associated with intraoperative use of noninvasive blood
      pressure (NIBP) cuffs, tourniquets, and intra-arterial catheters, and patient
      positioning in children with OI. METHODS: We retrospectively reviewed records of
      patients younger than 21 years with OI who underwent surgery with general
      anesthesia from 2010 to 2016 at our tertiary care center. The primary outcome of
      interest was iatrogenic fracture caused by NIBP cuff use, tourniquet use, or
      patient positioning. The secondary outcome of interest was complications
      associated with intra-arterial catheter use. RESULTS: Thirty-seven patients (15
      girls) with a mean age of 10+/-4.8 years underwent 96 orthopaedic procedures
      (lower extremity, upper extremity, and spine) and 2 nonorthopaedic procedures
      (myringotomy, dental rehabilitation). Blood pressure was monitored with NIBP
      cuffs in 81 surgeries and intra-arterial catheters in 17 surgeries. Tourniquets
      (all applied to the lower extremity at a pneumatic pressure of 250 mm Hg) were
      used to minimize bleeding in 30 surgeries. There were no iatrogenic fractures
      associated with NIBP cuff use. One patient had a left humerus fracture that
      occurred during preoperative patient positioning. There were no fractures
      associated with tourniquet use and no complications related to intra-arterial
      catheters. CONCLUSIONS: In pediatric patients with OI, intraoperative use of NIBP
      cuffs and tourniquets was not associated with iatrogenic fracture. There were no
      complications related to intra-arterial catheter use. Care should be used during
      the perioperative period to prevent fractures during body positioning. LEVEL OF
      EVIDENCE: Level IV.

PMID- 29189537
TI  - Bipolar Sealer Devices Used in Posterior Spinal Fusion for Neuromuscular
      Scoliosis Reduce Blood Loss and Transfusion Requirements.
AB  - BACKGROUND: Reducing perioperative blood loss and the need for transfusions in
      patients undergoing spinal surgery is especially important for those with
      neuromuscular disorders. These patients require extensive spino-pelvic exposure
      and are often medically fragile. We have used Amicar to decrease blood loss since
      2001. As an effort to further reduce blood loss and transfusions, we use a
      bipolar sealer device (Aquamantys) as an adjunct to electrocautery. We present
      the results of our first 64 neuromuscular patients to show the efficacy of the
      device. METHODS: Using a prospectively maintained database we reviewed the
      operative time, estimated perioperative blood loss, cell saver use, and
      intraoperative and postoperative transfusion rate in patients who underwent
      posterior spinal fusion for neuromuscular scoliosis. Sixty-four patients were
      identified who fit these criteria since the use of the bipolar sealer device was
      instituted.We compared these patients with a control group of the preceding 65
      patients in whom this device was not used for hemostasis. All patients, including
      those in the study group, received Amicar (infusion of 100 mg/kg over 15 to 20
      min, then 10 mg/kg/h throughout the remainder of the procedure). The surgical
      technique did not differ between the 2 groups. RESULTS: Baseline characteristics
      between the 2 groups were similar except for the number of patients having an all
      screw construct which was larger in the investigational group (25% vs. 8%,
      P=0.03). There were no significant differences in operative time or duration of
      hospital stay. Intraoperative blood loss was lower in the study group (741 mL) as
      compared with the control group (1052 mL, P=0.003). Total perioperative blood
      loss, however, showed no significant difference. Thirty-five (55%) patients in
      the study group and 50 (77%) patients in the control group required additional
      intraoperative or postoperative transfusions (P=0.01). The number of packed red
      cell units transfused per patient was 0.81 in the study group and 1.57 in the
      control group (P=0.001). Although the intraoperative cell saver transfusion was
      same, the total blood volume transfused, which includes cell saver and any other
      transfusions, was significantly lower in the study group, 425 mL versus 671 mL
      (P=0.002). CONCLUSIONS: Use of a bipolar sealer device in posterior spinal fusion
      for neuromuscular scoliosis significantly reduced intraoperative blood loss and
      transfusion rate when compared with a control group in this retrospective review.
      LEVEL OF EVIDENCE: Level III-retrospective comparative study.

PMID- 29189538
TI  - What's New in Pediatric Sports Conditions of the Knee?
AB  - BACKGROUND: Sports injuries are common in pediatric and adolescent patients and
      the evaluation and treatment of these injuries continues to evolve. The purpose
      of this review is to provide a comprehensive appraisal of the literature,
      highlighting recent updates on sports-related knee injuries in the pediatric
      athlete. We specifically examined literature on tibial spine fractures,
      osteochondritis dissecans (OCD) of the knee, and patellar instability. Because of
      the volume of literature on the subject, pediatric, and adolescent anterior
      cruciate ligament injuries were not included in this review. METHODS: An
      electronic search of the PubMed, EMBASE, and Google Scholar databases was
      performed for keywords related to pediatric: tibial spine fractures, patellar
      instability, and osteochondritis dissecans (OCD). Search results were filtered by
      publication date to yield articles published electronically or in print on or
      after January 1, 2013. Papers were selected based on expert opinion and consensus
      by the authors and included if deemed to have contributed important findings to
      the above topics. RESULTS: A total of 31 articles were deemed to have contributed
      significant findings to the literature: 5 tibial spine, 17 patellar instability,
      and 9 OCD. The level of evidence for most studies was either level III or IV.
      CONCLUSIONS: The optimal treatment for tibial spine fractures remains
      controversial. The evaluation of risk factors for recurrent patellar instability
      is important in determining the optimal treatment strategy following first-time
      patellar dislocation. Future multicenter studies on pediatric OCD have the
      potential to further understanding of this difficult problem. High-level,
      comparative outcomes research on a variety of pediatric sports related injuries
      is lacking and this review may help inform topics for future study. LEVEL OF
      EVIDENCE: Level IV-literature review.

PMID- 29189539
TI  - Effect of Continuous Systemic Administration of Esmolol on Intraocular Pressure
      During Surgery in a Sustained Steep Trendelenburg Position.
AB  - PURPOSE: To investigate the effects of continuous systemic administration of
      esmolol on intraocular pressure (IOP) during laparoscopic and robotic surgeries
      for recto-sigmoid cancer in a steep Trendelenburg position. MATERIALS AND
      METHODS: A total of 50 patients undergoing laparoscopic surgery in a steep
      Trendelenburg position were included. Patients in the esmolol (E) group received
      a 0.25 mg/kg IV loading dose of esmolol before anesthesia, followed by an
      infusion of 15 MUg/kg/min throughout the operation. Patients in the saline (S)
      group were infused with the same volume of normal saline. IOP and ocular
      perfusion pressure were measured 16 times: before anesthetic induction (T1),
      before administration of the study drug (T2), after administration of anesthetic
      induction agents (T3), after tracheal intubation (T4), 1, 3, 5, and 10 minutes
      after tracheal intubation (T5-T8), immediately after intraperitoneal CO2
      insufflation (T9), immediately after the steep Trendelenburg position (T10), 1,
      2, and 4 hours after the steep Trendelenburg position (T11-T13), just before the
      supine position (T14), and 10 and 30 minutes after the supine position (T15,
      T16). RESULTS: The IOP increased markedly after adopting the steep Trendelenburg
      position, reaching 28.8+/-4.4 mm Hg in group S. The IOP at T13 in group S was
      ~5.7 mm Hg higher than in group E. The IOP at T13 was ~10.6 mm Hg higher than in
      T1 in group S, but only ~4.4 mm Hg higher than in group E. CONCLUSIONS:
      Continuous systemic administration of esmolol can alleviate the increase in IOP
      during a sustained steep Trendelenburg position without adverse cardiovascular
      effects.

PMID- 29189540
TI  - The Short-term Effect of Subtenon Sponge Application Versus Subtenon Irrigation
      of Mitomycin-C on the Outcomes of Trabeculectomy With Ex-PRESS Glaucoma
      Filtration Device: A Randomized Trial.
AB  - PURPOSE: Traditionally, during trabeculectomy, Mitomycin-C (MMC) is applied to
      the tissues using surgical sponges. However, alternate modes of application
      exist. This study assessed the success rates, complication rates, final
      intraocular pressure (IOP), and bleb characteristics between patients receiving
      subtenon MMC application by sponge versus irrigation. PATIENTS AND METHODS: A
      total of 100 patients with glaucoma were enrolled and each was randomized to 1 of
      the 2 treatment groups. Patients underwent trabeculectomy with Ex-PRESS shunt and
      MMC placement and were followed for 6 months. Complication rates assessed
      included bleb failure, bleb leaks, bleb encapsulation, and hypotony, amongst
      others. Additional factors evaluated included bleb morphology, glaucoma drop
      usage, Fluorouracil (5-FU) application, bleb revision, and subsequent glaucoma
      surgery. RESULTS: The irrigation method provided greater IOP lowering effects
      (P=0.03); correspondingly the irrigation group had higher rates of hypotony
      (P=0.03) but with no significant consequences. Patients who had trabeculectomy/Ex
      PRESS alone had greater IOP reduction than those who had concurrent cataract
      surgery (P<0.001). The sponge group had higher rates of 5-FU use (P=0.007) and
      higher reoperation rates (P=0.02) when compared with the irrigation group.
      Success was defined as achieving 4 mm Hg<=IOP<=15 mm Hg without any anatomical
      bleb failure or subsequent glaucoma surgery. The overall success rate was 87%.
      CONCLUSIONS: Application of subtenon MMC by irrigation seems to provide improved
      short-term outcomes compared with application with sponges. With a similar safety
      profile, the irrigation method provides better IOP control, and decreases the
      need for further clinical/surgical intervention in the short-term after
      trabeculectomy. Longer-term studies will be useful in analyzing if these
      differences persist with time.

PMID- 29189541
TI  - A Comparison of Retrobulbar Versus Topical Anesthesia in Trabeculectomy and
      Aqueous Shunt Surgery.
AB  - PURPOSE: The purpose of this study was to compare the required supplemental
      anesthesia and postoperative patient pain score in individuals undergoing
      glaucoma surgery under topical anesthesia (TA) versus retrobulbar anesthesia
      (RB). MATERIALS AND METHODS: A retrospective, interventional, comparative cohort
      study of 261 eyes of 225 patients undergoing glaucoma and combined glaucoma with
      cataract surgery were included in the study. The main outcome measures were the
      amount of supplemental, systemic intraoperative anesthesia used and the
      postoperative pain scale between patients undergoing TA versus RB anesthesia. A
      secondary analysis was performed between combined glaucoma and cataract surgery
      versus glaucoma surgery alone. RESULTS: About 6.2% patients complained of pain
      after glaucoma surgery (8.1% among TA group and 3.1% among RB group; P=0.049).
      Overall, pain tended to be mild with a mean score of 0.32 of 10 for TA and 0.08
      of 10 for RB (P=0.027). The amount of IV anesthetics used intraoperatively was
      lower in the RB anesthesia compared with the TA group (midazolam, P=0.042;
      fentanyl, P<0.001; propofol, P<0.001). In addition, patients undergoing RB
      anesthesia were less likely to use postoperative pain medication (P<0.001). There
      was no difference in pain score (P=0.707) or in the amount of IV anesthetics (all
      P>0.350) between eyes undergoing combined versus glaucoma surgery alone.
      CONCLUSIONS: Although supplemental anesthesia and pain scores were statistically
      increased in the topical group, the prevalence and the severity of pain was low.
      Therefore, TA is feasible and a reasonable option for glaucoma surgery.
      Furthermore, this conclusion applies when glaucoma surgery is performed alone or
      in combination with the other eye surgery.

PMID- 29189542
TI  - Implantation of a CyPass Supraciliary Stent Combined With Targeted iStent
      Trabecular Microbypass Stents in a Phakic Patient With Primary Open-angle
      Glaucoma.
AB  - PURPOSE: To report the first successful implantation of a CyPass supraciliary
      stent combined with 2 targeted iStent trabecular microbypass stents in a phakic
      primary open-angle glaucoma patient with markedly elevated intraocular pressures
      (IOP) on maximum tolerable medical therapy. METHODS: Case report. RESULTS: A 52
      year-old phakic male patient with primary open-angle glaucoma with uncontrolled
      IOP in the right eye (OD) of 36 mm Hg on maximal topical pharmacotherapy. The
      patient underwent implantation of a single CyPass supraciliary stent combined
      with the targeted implantation of 2 iStent trabecular microbypass stents, 1 right
      facing stent and 1 left facing stent. Postoperatively, off of all glaucoma
      medications, the IOP decreased to 10 mm Hg on day 1 and continued to be
      controlled between 10 to 13 mm Hg until postoperative month 6, with only 1
      glaucoma medication added after postoperative month 5. In addition, there were no
      postoperative complications to date. CONCLUSIONS: The combined implantation of a
      CyPass supraciliary stent and iStent trabecular microbypass stents can
      successfully lower IOP and decrease medication burden with minimal risk for
      complications.

PMID- 29189543
TI  - Acute Angle-closure Glaucoma Associated With Aripiprazole in the Setting of
      Plateau Iris Configuration.
AB  - PURPOSE OF THE STUDY: The purpose of this study was to report a novel case of
      drug-induced angle-closure from aripiprazole (Abilify), an atypical
      antipsychotic, and propose a mechanism for this association. METHODS/RESULTS: We
      report a case of a 45-year-old white woman who presented in subacute angle
      closure 2 months after initiating aripiprazole 5 mg daily for depression. This
      patient reported no prior ocular history and had been on longstanding duloxetine
      (Cymbalta) 60 mg daily for over 10 years before starting aripiprazole.
      Examination at initial presentation revealed an intraocular pressure (IOP) of 16
      mm Hg in the right eye and an elevated IOP of 44 mm Hg in the left eye.
      Gonioscopy demonstrated a plateau iris configuration in the right eye and angle
      closure with a plateau iris configuration in the left eye. She was started on IOP
      lowering therapy and underwent a laser peripheral iridotomy. Despite
      recommendation to discontinue aripiprazole, duloxetine was discontinued;
      aripiprazole was maintained and later increased to 10 mg daily for worsening
      depression. Three months after the dosage increase, the patient was found to have
      an elevated IOP of 32 mm Hg and angle-closure with a plateau iris configuration
      in the left eye. Iridoplasty was performed in the left eye with subsequent
      opening of the angle and improvement in IOP. The second attack of angle-closure
      led to the discontinuation of aripiprazole and a corresponding widening of the
      angles in both eyes 1 week after cessation. CONCLUSIONS: This is the first report
      to describe drug-induced angle-closure glaucoma associated with aripiprazole use.
      The mechanism of angle closure, we hypothesize, is from mydriasis and/or
      supraciliary effusion mediated by the serotoninergic effect on the iris and
      ciliary body complex. Treatment is preferably cessation of the medication.
      However, in cases where the medication is necessary for management of major
      depression, iridoplasty should be performed to reduce the risk of angle closure.

PMID- 29189545
TI  - The Role of Dissemination in Promotion and Tenure for Public Health.

PMID- 29189544
TI  - Is Obstructive Sleep Apnea Associated With Progressive Glaucomatous Optic
      Neuropathy?
AB  - PURPOSE: The purpose of this study was to evaluate the relationship between
      obstructive sleep apnea syndrome (OSAS) and glaucoma progression, and to examine
      the correlation between OSAS severity and rate of visual field (VF) loss.
      METHODS: Patients with concurrent diagnoses of open-angle glaucoma and OSAS
      between 2010 and 2016 were identified. Enrollment criteria consisted of
      glaucomatous optic neuropathy and VF loss, >=5 reliable VFs, >=2 years of follow
      up, and polysomnography (PSG) within 12 months of final VF. PSG parameters
      including apnea-hypopnea index (AHI) and oxygen saturation (SpO2) were collected.
      Eyes were classified as "progressors" or "nonprogressors" based upon event
      analysis using Glaucoma Progression Analysis criteria. Two-tailed t test
      comparisons were performed, and correlations between rates of VF loss and PSG
      parameters were assessed. RESULTS: A total of 141 patients with OSAS and glaucoma
      were identified. Twenty-five patients (age 67.9+/-7.6 y) with OSAS (8 mild, 8
      moderate, 9 severe) were enrolled. Eleven eyes (44%) were classified as
      progressors, and had more severe baseline VF loss (P=0.03). Progressors and
      nonprogressors had nonsignificantly different (P>0.05) age (69.9+/-8.7 vs. 66.4+/
      6.6 y), follow-up (4.4+/-0.7 vs. 4.3+/-1.0 y), intraocular pressure (13.1+/-2.8
      vs. 14.9+/-2.5 mm Hg), mean ocular perfusion pressure (49.7+/-5.5 vs. 48.8+/-9.0
      mm Hg), AHI (31.3+/-18.6 vs. 26.4+/-24.0), body-mass index (27.8+/-5.5 vs. 28.8+/
      5.6), and SpO2 (94.1+/-1.6% vs. 94.0+/-1.6%). AHI was not correlated with slopes
      of VF mean deviation (r, -0.271; P, 0.190) or pattern standard deviation (r,
      0.211; P, 0.312), and no substantial increase in risk of progression was found
      with increase in AHI. CONCLUSIONS: This study does not support a relationship
      between OSAS and glaucomatous progression. No correlation was observed between
      OSAS severity and rate of VF loss.

PMID- 29189546
TI  - What State Health Officials Wish They Had Known and How They Learned Best.

PMID- 29189547
TI  - Love as a Public Health Intervention.

PMID- 29189548
TI  - Impact of the NACCHO Retail Program Standards Mentorship Program on Retail Food
      Regulatory Programs.

PMID- 29189549
TI  - Outcome of Guillain-Barre Syndrome in Tertiary Care Centers in Thailand.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS), a common acute polyneuropathy, is seen
      worldwide with significant morbidity and mortality. GBS consists of a number of
      subtypes. OBJECTIVE: The aim of this study is to identify clinical
      characteristics, electrophysiologic changes, clinical course, treatment, and
      outcome of GBS in Thailand. MATERIAL AND METHODS: Retrospective study of GBS
      patients aged 15 years or older, admitted to Thammasat University Hospital and
      Bangkok Hospital Medical Center between January 1, 2009 and November 30, 2014.
      RESULTS: Thirty patients were found. Demographic characteristics were collected
      and described as follows; 60% male sex; average age 54 years; Asian 60%, European
      20%, and others 10%. Disease subtypes consist of acute inflammatory demyelinating
      polyneuropathy 66.7%, acute motor axonal neuropathy 10%, and others 23.3%.
      Average GBS disability score at admission was 2.9. Immunotherapy was intravenous
      immunoglobulin 83.3%, plasma exchange 3.3%, and steroid 3.3%. Average length of
      stay was 14.2 days; assisted ventilation rate was 13.3%. After the average of 1
      year follow-up, average GBS disability score was 1.8, good outcome (score <3) was
      63.3% and no death. CONCLUSIONS: Our study suggests that most GBS patients in
      Thailand are acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
      subtype and have a good outcome. Predictors of severe disability are older age,
      previous diarrhea, autonomic disturbances, severe limb or bulbar weakness at
      admission, or onset of treatment.

PMID- 29189550
TI  - Pediatric CIDP: Clinical Features and Response to Treatment.
AB  - OBJECTIVES: Childhood chronic inflammatory demyelinating polyradiculoneuropathy
      (CIDP) responds favorably to immunomodulatory treatment. However, the optimal
      sequencing and selection of immunotherapy is uncertain. METHODS: Using accepted
      diagnostic criteria, pediatric patients with CIDP seen at our center from 1999 to
      2015 were identified retrospectively through medical record review. Clinical
      details and treatment responses were tabulated. RESULTS: Ten patients (age 4-16,
      6 women) with definite (N = 8) or possible (N = 2) CIDP met criteria. All were
      initially treated with IVIg; 6 responded but 4 did not. All 4 IVIG nonresponders
      improved with twice-weekly high-dose oral prednisone, as did 1 IVIg responder who
      was also treated with twice-weekly oral prednisone when IVIg was discontinued.
      Pulse steroids were well tolerated. CONCLUSIONS: Pulse oral corticosteroid
      therapy holds promise as an alternative treatment to IVIG in pediatric CIDP.
      Future multicenter studies are warranted to determine the comparative efficacy
      and safety of weekly pulse oral corticosteroids versus IVIg in pediatric CIDP.

PMID- 29189551
TI  - Distinguishing Features of the Repetitive Nerve Stimulation Test Between Lambert
      Eaton Myasthenic Syndrome and Myasthenia Gravis, 50-Year Reappraisal.
AB  - OBJECTIVE: To reappraise the distinguishing features of the repetitive nerve
      stimulation (RNS) tests in the abductor digiti quinti muscle between myasthenia
      gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) 50 years after the
      1965's Lambert seminal paper. METHODS: The various parameters of the RNS test
      were compared between 34 patients with LEMS and 140 patients with MG to assess
      their diagnostic sensitivity. RESULTS: RNS test was abnormal in all (100%)
      patients with LEMS and 76 (54%) patients with MG. The diagnostic hallmark of
      LEMS, >=60% increment at high-rate stimulation or postexercise facilitation, was
      present in 33 (97%) of patients. The diagnostic hallmark of MG, decrement at low
      rate stimulation (LRS), was present in 65 (46%) of patients with MG. The most
      prominent difference in the various parameters of RNS tests was noted between
      LEMS versus MG and normal controls. CONCLUSIONS: Distinguishing features of the
      RNS test in LEMS and MG are confirmed in this direct comparison study: the low
      compound muscle action potential amplitude, decrement at LRS, and increment at
      high-rate stimulation or postexercise facilitation for LEMS and normal compound
      muscle action potential amplitude and decrement at LRS for MG.

PMID- 29189552
TI  - Autonomic Reflex Screen Test Abnormalities in Cold-Induced Sweating Syndrome Type
      1.
AB  - Cold-induced sweating syndrome (CISS) is a rare autosomal recessive disease due
      to mutation in the Cytokine receptor-like factor 1 (CRLF1). The characteristic
      symptom of CISS is the tendency to sweat profusely especially in the upper body
      and hands when the patient is exposed to cold temperature. We sought to first
      report the findings of autonomic reflex screen in a case of CISS type 1 with
      Cytokine receptor-like factor 1 mutation. Valsalva morphology, Valsalva ratio,
      and heart rate response to deep breathing were normal for the patient's age.
      Quantitative sudomotor axon reflex test showed nonlength dependent decrease in
      the sweat volume. Tilt table revealed evidence of reflex (vasovagal) "syncope,"
      however, the patient was asymptomatic without loss of consciousness.

PMID- 29189553
TI  - Guillain-Barre Syndrome Triggered by Immune Checkpoint Inhibitors: A Case Report
      and Literature Review.
AB  - Immune checkpoint inhibitors, used as immunotherapy in the treatment of melanoma
      and refractory cancer, may trigger autoimmune disorders. We describe a case of
      Guillain-Barre syndrome (GBS) after the treatment with ipilimumab and nivolumab
      and review 4 other reported cases. We confirmed the diagnosis of GBS by
      electrodiagnostic and cerebrospinal fluid studies. Electrodiagnostic results
      showed findings consistent with acquired demyelinating polyneuropathy and
      cerebrospinal fluid showed albuminocytologic dissociation. All patients were
      treated with intravenous immunoglobulin or other immunomodulating therapy. Among
      5 cases which include our patient, 2 did well, 1 did not improve, and 2 died of
      respiratory insufficiency and multiorgan failure. Enhancing T-cell activation
      from immune checkpoint inhibitors may trigger GBS which should be suspected when
      progressive weakness and areflexia occur after treatment with immune checkpoint
      inhibitors.

PMID- 29189554
TI  - Paraneoplastic Lambert-Eaton Myasthenic Syndrome With Limbic Encephalitis:
      Clinical Correlation With the Coexistence of Anti-VGCC and Anti-GABAB Receptor
      Antibodies.
AB  - OBJECTIVE: To characterize Lambert-Eaton myasthenic syndrome and limbic
      encephalitis with coexistent voltage-gated calcium channel (VGCC) antibody and
      gamma-aminobutyric acid (GABA) B receptor antibody. METHODS: Case study. RESULTS:
      A 57-year-old man presented with 6 months of weakness, unsteadiness, and vision
      difficulties. Examination revealed proximal weakness and diminished reflexes.
      Electrodiagnostic study revealed low-amplitude motor potentials and facilitation
      on high-frequency stimulation. Laboratory evaluation identified P/Q-type VGCC
      antibody. Positron emission tomography identified a mediastinal lesion, confirmed
      as small-cell lung carcinoma. The patient developed confusion and seizures.
      Cerebrospinal fluid analysis identified antibodies to GABAB receptor.
      CONCLUSIONS: This case describes a patient with Lambert-Eaton myasthenic
      syndrome, limbic encephalitis, and autoantibodies to VGCC and GABAB receptor.
      Atypical presentation of paraneoplastic neurological syndromes could indicate the
      presence of a second antibody that may have significant impact on therapy.

PMID- 29189555
TI  - What is in the Literature?
AB  - This edition of "What is in the Literature?" will focus on motor neuron disease
      (MND), including adult forms [amyotrophic lateral sclerosis (ALS), progressive
      muscular atrophy (PMA), primary lateral sclerosis (PLS), progressive bulbar palsy
      (PBA), and monomelic mononeuropathy (MMND)], and childhood forms [spinal muscle
      atrophy (SMA)].

PMID- 29189556
TI  - Atypical Asymmetric Guillain-Barre Syndrome With Acute Rhabdomyolysis.

PMID- 29189557
TI  - Unusual Case of Facioscapulohumeral Dystrophy.

PMID- 29189558
TI  - Paraneoplastic Necrotizing Myopathy Associated With Neuroendocrine Carcinoma.

PMID- 29189559
TI  - Weakness, Hypokalemia, and Dengue.

PMID- 29189560
TI  - Vitamin D Status and Its Association With Quality of Life, Physical Activity, and
      Disease Activity in Rheumatoid Arthritis Patients.

PMID- 29189561
TI  - Symptomatic Cryofibrinogenemia Following Trauma.

PMID- 29189562
TI  - Pulmonary Pasteurellosis in a Patient Treated With Tocilizumab for Rheumatoid
      Arthritis.

PMID- 29189563
TI  - Osteomyelitis Variolosa, A Differential Diagnosis of a Multifaceted Condition.

PMID- 29189564
TI  - Coronary Artery Inflammation in Rheumatoid Arthritis Using Fluorine-18
      Fluorodeoxyglucose Positron Emission Tomography.

PMID- 29189567
TI  - Transfusion of Red Blood Cells Stored More Than 28 Days is Associated With
      Increased Morbidity Following Spine Surgery.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to
      describe the association between storage duration of packed red blood cells
      (PRBCs) and perioperative adverse events in patients undergoing spine surgery at
      a tertiary care center. SUMMARY OF BACKGROUND DATA: Despite retrospective studies
      that have shown that longer PRBC storage duration worsens patient outcomes,
      randomized clinical trials have found no difference in outcomes. However, no
      studies have examined the impact of giving the oldest blood (28 days old or more)
      on morbidity within spine surgery. METHODS: The surgical administrative database
      at our institution was queried for patients transfused with PRBCs who underwent
      spine surgery between December 4, 2008, and June 26, 2015. Patients undergoing
      spinal fusion, tumor-related surgeries, and other identified spine surgeries were
      included. Patients were divided into two groups on the basis of storage duration
      of blood transfused: exclusively <=28 days' storage or exclusively >28 days'
      storage. The primary outcome was composite in-hospital morbidity, which included
      (1) infection, (2) thrombotic event, (3) renal injury, (4) respiratory event,
      and/or (5) ischemic event. RESULTS: In total, 1141 patients who received a
      transfusion were included for analysis in this retrospective study; 710 were
      transfused exclusively with PRBCs <=28 days' storage and 431 exclusively with
      PRBCs >28 days' storage. Perioperative complications occurred in 119 patients
      (10.4%). Patients who received blood stored for >28 days had higher odds of
      developing any one complication [odds ratio (OR) = 1.82; 95% confidence interval
      (95% CI), 1.20-2.74; P = 0.005] even after adjusting for competing perioperative
      risk factors. CONCLUSION: Blood stored for >28 days is independently associated
      with higher odds of developing perioperative complications in patients transfused
      during spinal surgery. Our results suggest that blood storage duration may be an
      appropriate parameter to consider when developing institutional transfusion
      guidelines that seek to optimize patient outcomes. LEVEL OF EVIDENCE: 3.

PMID- 29189568
TI  - Tranexamic Acid Decreases Visible and Hidden Blood Loss Without Affecting
      Prethrombotic State Molecular Markers in Transforaminal Thoracic Interbody Fusion
      for Treatment of Thoracolumbar Fracture-Dislocation.
AB  - STUDY DESIGN: A randomized, double-blind, placebo-controlled clinical trial.
      OBJECTIVE: To evaluate the efficacy and safety of tranexamic acid (TXA)
      administered during the surgical correction of thoracolumbar fracture
      dislocation. SUMMARY OF BACKGROUND DATA: Thoracolumbar fracture-dislocation
      surgery is generally associated with substantial blood loss and a high risk of
      deep vein thrombosis. TXA has been shown to improve hemostasis in surgical
      procedures. METHODS: We investigated 80 patients with thoracolumbar fracture
      dislocation who underwent transforaminal thoracic interbody fusion between March
      2014 and December 2016. The patients were randomized into the TXA (n = 39) and
      Placebo (n = 41) groups, according to whether they did or did not receive pre-
      and intraoperative TXA treatment. The two groups were compared for demographic
      characteristics as well as pre- and postoperative levels of prethrombosis-state
      molecular markers and visible and hidden blood loss volumes. Additionally, the
      prevalence of TXA-related complications was determined. RESULTS: The two groups
      did not differ significantly in demographic characteristics. The visible blood
      loss (intra- and postoperative bleeding during the first 24 h), hidden blood
      loss, and true total blood loss during surgery in the TXA group were
      significantly lower than those in the Placebo group (835 +/- 180.3 mL, 351 +/-
      82.3 mL, 1385 +/- 102.3 mL vs. 1155 +/- 175.3 mL, 564 +/- 170.5 mL, 1683 +/-
      121.0 mL, respectively; P < 0.01). Furthermore, the levels of the prethrombosis
      state molecular markers GMP-140, fibrinogen, fibrin degradation products, and D
      dimer were higher in the TXA group than in the Placebo group, although the
      differences were not significant (P > 0.05). No significant intergroup
      differences were noted in the prevalence of deep venous thrombosis and pulmonary
      embolus during the study period. CONCLUSION: TXA significantly reduced visible
      and hidden blood loss without affecting the prethrombosis-state molecular markers
      in transforaminal thoracic interbody fusion or causing any notable adverse
      effects. LEVEL OF EVIDENCE: 3.

PMID- 29189569
TI  - Common Variant of POC5 Is Associated With the Susceptibility of Adolescent
      Idiopathic Scoliosis.
AB  - STUDY DESIGN: A case-control study. OBJECTIVE: To validate the relationship
      between POC5 and adolescent idiopathic scoliosis (AIS) in the Chinese patients
      and to further investigate the functional role of POC5. SUMMARY OF BACKGROUND
      DATA: Three rare functional variants in the POC5 were recently reported to be
      strongly associated with the disease in a large family with multiple members
      affected with idiopathic scoliosis. To our knowledge, the association between the
      mutations of POC5 and AIS remains undetermined in the Chinese population.
      METHODS: Single nucleotide variants c.1336G>A, c.1286C>T, and c.1363G>C of POC5
      were genotyped in 2432 patients with AIS and 2292 healthy controls using multiple
      ligase detection reactions. Common variants covering POC5 gene were genotyped in
      1446 patients and 2080 controls. The mRNA expression of POC5 was determined in
      the paraspinal muscles collected from 98 patients and 28 controls. The Student t
      test was used to compare mRNA expression level between the patients and the
      controls. In addition, the POC5 expression was compared among different genotypes
      of the remarkably associated single nucleotide polymorphism (SNP) with analysis
      of variance test. RESULTS: There was no case of mutation for the three reported
      variants of POC5. SNP rs6892146 was observed to have significantly different
      distribution of minor allele frequency in the two group (0.485 vs. 0.446, P =
      0.004). The mRNA expression of POC5 was 1.5-fold higher in patients than in the
      controls (0.00012 +/- 0.00009 vs. 0.00008 +/- 0.00006, P = 0.02). Patients with
      genotype GG have a significantly increased expression of POC5 than those with CC
      (0.00014 +/- 0.00007 vs. 0.00009 +/- 0.00007, P = 0.03). CONCLUSION: Common
      variant rs6892146 of POC5 is associated with the development of AIS in the
      Chinese population. Targeted regional sequencing of POC5 may help identify novel
      mutations associated with AIS. LEVEL OF EVIDENCE: 4.

PMID- 29189570
TI  - Facet Sagittal Orientation: Possible Role in the Pathology of Degenerative Lumbar
      Spinal Stenosis.
AB  - STUDY DESIGN: A retrospective case-control study. OBJECTIVE: This study aimed to
      elucidate the association between facet joint orientation and degenerative lumbar
      spinal stenosis (DLSS). SUMMARY OF BACKGROUND DATA: Many studies have
      demonstrated the relationship between sagittal facet orientation and degenerative
      lumbar spondylolisthesis. However, the associations between facet orientation and
      DLSS have rarely been studied. METHODS: Ninety-one age-matched and sex-matched
      patients with DLSS (LSS group) and 91 control participants were consecutively
      enrolled. Their lumbar facet angles and the dural sac cross-sectional area at L2
      L3, L3-L4, L4-L5, and L5-S1 were measured using axial magnetic resonance imaging.
      The intersection angle of the midsagittal line of the vertebra to the facet line
      represents the orientation of the facet joint. RESULTS: The facet angles on the
      left side or right side of the LSS group were significantly smaller than the
      respective ones of the control group. Outcomes of the groups revealed
      significantly and consistently increasing facet angles from L2-L3 to L5-S1. The
      dural sac cross-sectional area of the LSS group had significantly smaller
      measurements values than that of the control group at L2-L3, L3-L4, L4-L5, and L5
      S1. CONCLUSION: Sagittalization of lumbar facet joints was considered to be a
      risk factor for DLSS and may play a role in the pathology of DLSS. LEVEL OF
      EVIDENCE: 3.

PMID- 29189571
TI  - Adding Satellite Rods to Standard Two-rod Construct With the Use of Duet Screws:
      An Effective Technique to Improve Surgical Outcomes and Preventing Proximal
      Junctional Kyphosis in Posterior-Only Correction of Scheuermann Kyphosis.
AB  - STUDY DESIGN: A retrospective matched-cohort comparative study. OBJECTIVE: The
      aim of this study was to compare the surgical results after the use of duet screw
      based satellite rods and bilateral satellite rods (S-RC) versus a standard two
      rod construct (2-RC) across osteotomy sites in a matched cohort with Scheuermann
      kyphosis (SK). SUMMARY OF BACKGROUND DATA: Multiple Ponte osteotomies are
      frequently employed to correct SK via a posterior-only approach, with a 2-RC
      across the osteotomy sites. Whereas, correction rate and junction problems remain
      as the major concerns. METHODS: This study reviewed a consecutive series of
      patients with SK who had undergone posterior-only correction with multilevel
      Ponte osteotomy between 2009 and 2014 and had been followed over 24 months.
      Twenty-two patients receiving placement with an S-RC with the use of duet screws
      were identified and closely matched with 22 patients with a 2-RC in terms of age,
      apex, and magnitude of kyphosis. Comparisons were made with regards to deformity
      magnitude, correction results, complications, and clinical outcomes between the
      two groups. RESULTS: No significant difference was found between groups in
      preoperative patient's factors (age, gender, apex, magnitude of kyphosis, and SRS
      22 scores) and surgical factors (blood loss, operation time, osteotomy levels,
      and fused levels). Compared with the 2-RC group, the S-RC group had higher
      correction rate (55.4% +/- 7.5% vs. 46.2% +/- 5.1%, P < 0.001), less correction
      loss (1.0 +/- 0.8 degrees  vs. 2.4 +/- 1.4 degrees , P < 0.001) during the follow
      up, and higher improvement of back pain as well (P < 0.05). None were detected
      with pseudarthrosis or implant failure in either group, but proximal junctional
      kyphosis was less frequently seen in S-RC group (1 of 22) than 2-RC group (7 of
      22) (P < 0.05). CONCLUSION: As a safe method, use of S-RC is effective in
      providing increased kyphotic correction across multiple Ponte osteotomy levels,
      and improving patient-reported outcomes of management satisfaction and back pain.
      The biomechanical benefits of stress dispersion, coupled with increased stability
      and weight bearing ability, make it a powerful technique preventing correction
      loss and proximal junctional kyphosis. LEVEL OF EVIDENCE: 3.

PMID- 29189572
TI  - Immunomodulation of Human Mesenchymal Stem/Stromal Cells in Intervertebral Disc
      Degeneration: Insights From a Proinflammatory/Degenerative Ex Vivo Model.
AB  - STUDY DESIGN: Ex vivo experimental study. OBJECTIVE: To investigate the effect of
      proinflammatory/degenerative intervertebral disc (IVD) microenvironment on the
      regenerative and immunomodulatory behavior of mesenchymal stem/stromal cells
      (MSCs), using an ex vivo model from bovine origin. SUMMARY OF BACKGROUND DATA:
      Low back pain is a cause of disability worldwide, most frequently associated with
      IVD degeneration and inflammation, and characterized by increased levels of
      inflammatory mediators, often disregarded. MSC-based therapies to low back pain
      have been advocated, but the involvement of inflammation in IVD remodeling
      mechanism, promoted by MSCs has not yet been explored. METHODS: Bovine IVD organ
      cultures of nucleus pulposus punches were stimulated with needle puncture and
      culture medium supplementation with 10 ng/mL of interleukin (IL)-1beta, to induce
      a proinflammatory/degenerative environment, as previously established. Human bone
      marrow-derived MSCs were cultured on top of transwells, placed above nucleus
      pulposus punches, for up to 16 days. MSCs were analyzed by screening cell
      viability/apoptosis, metabolic activity, migration, and inflammatory cytokines
      production in response to the proinflammatory environment. IVD extracellular
      matrix (ECM) remodeling, gene expression profile of IVD cells, and inflammatory
      cytokine profile in the presence of MSCs in basal versus proinflammatory
      conditions were also evaluated. RESULTS: Proinflammatory/degenerative IVD
      conditions did not affect MSCs viability, but promoted cell migration, while
      increasing IL-6, IL-8, monocyte chemoattractant protein-1, and prostaglandin E2
      and reducing transforming growth factor-beta1 production by MSCs. MSCs did not
      stimulate ECM production (namely type II collagen or aggrecan) in neither basal
      nor inflammatory conditions, instead MSCs downregulated bovine proinflammatory IL
      6, IL-8, and TNF-alpha gene expression levels in IL-1beta-stimulated IVDs.
      CONCLUSION: The present study provides evidence for an immunomodulatory paracrine
      effect of MSCs in degenerated IVD without an apparent effect in ECM remodeling,
      and suggest an MSCs mechanism-of-action dependent on a cytokine feedback loop.
      LEVEL OF EVIDENCE: 5.

PMID- 29189573
TI  - Quality of Life and Health Utility Scores Among Canadians Living With Traumatic
      Spinal Cord Injury - A National Cross-Sectional Study.
AB  - STUDY DESIGN: National, multicenter, cross-sectional study. OBJECTIVE: The goal
      of this study was to provide overall quality of life (QOL) and health utility
      (HU) values for patients with traumatic spinal cord injury (SCI) stratified by
      injury level and neurological status. SUMMARY OF BACKGROUND DATA: Traumatic SCI
      is a leading cause of disability. Varying injury level and severity generate a
      spectrum of neurological dysfunction and reduction in long-term QOL. METHODS: The
      Canadian SCI Community Survey was sent to Canadians living in the community after
      SCI. The impact of demographics, complications, and SCI classification on QOL was
      assessed using Analysis of variance, multiple linear regressions and ordinal
      logistic regression analyses. RESULTS: There were 1109 respondents with traumatic
      SCI. american spinal injury association impairment scale (AIS) grade was reported
      to be cervical motor complete in 20%, cervical motor incomplete in 28%,
      thoracolumbar motor complete in 32%, thoracolumbar motor incomplete in 16%, and
      normal (any level) in 1%. Injury level or AIS grade had no impact on either HU or
      QOL. The physical component of health-related quality of life (HRQOL) was
      significantly affected by the neurological level, but not the social or mental
      components. With a mean health utility score of 0.64 +/- 0.12, SCI patients
      living in the community reported having HRQOL similar to patients after total
      knee arthroplasty or lumbar spinal stenosis decompression. CONCLUSION: QOL or HU
      measured by generic HRQOL outcome tools should not be used as outcomes to assess
      the effectiveness of interventions targeting neurological function in traumatic
      SCI. A disease-specific instrument that captures the nuances specific to spinal
      cord injury patients is required. LEVEL OF EVIDENCE: 1.

PMID- 29189574
TI  - The Role of Mental Health Disease in Potentially Preventable Hospitalizations:
      Findings From a Large State.
AB  - BACKGROUND: Preventable hospitalizations are markers of potentially low-value
      care. Addressing the problem requires understanding their contributing factors.
      OBJECTIVE: The objective of this study is to determine the correlation between
      specific mental health diseases and each potentially preventable hospitalization
      as defined by the Agency for Healthcare Research and Quality. DESIGN/SUBJECTS:
      The Texas Inpatient Public Use Data File, an administrative database of all Texas
      hospital admissions, identified 7,351,476 adult acute care hospitalizations
      between 2005 and 2008. MEASURES: A hierarchical multivariable logistic regression
      model clustered by admitting hospital adjusted for patient and hospital factors
      and admission date. RESULTS: A total of 945,280 (12.9%) hospitalizations were
      potentially preventable, generating $6.3 billion in charges and 1.2 million
      hospital days per year. Mental health diseases [odds ratio (OR), 1.25; 95%
      confidence interval (CI), 1.22-1.27] and substance use disorders (OR, 1.13; 95%
      CI, 1.12-1.13) both increased odds that a hospitalization was potentially
      preventable. However, each mental health disease varied from increasing or
      decreasing the odds of potentially preventable hospitalization depending on which
      of the 12 preventable hospitalization diagnoses were examined. Older age (OR,
      3.69; 95% CI, 3.66-3.72 for age above 75 years compared with 18-44 y), black race
      (OR 1.44; 95% CI, 1.43-1.45 compared to white), being uninsured (OR 1.52; 95% CI,
      1.51-1.54) or dual-eligible for both Medicare and Medicaid (OR, 1.23; 95% CI,
      1.22-1.24) compared with privately insured, and living in a low-income area (OR,
      1.20; 95% CI, 1.17-1.23 for lowest income quartile compared with highest) were
      other patient factors associated with potentially preventable hospitalizations.
      CONCLUSIONS: Better coordination of preventative care for mental health disease
      may decrease potentially preventable hospitalizations.

PMID- 29189575
TI  - Incomplete Comparisons Between the Predictive Power of Data From Administrative
      Claims and Electronic Health Records.

PMID- 29189576
TI  - Predicting High Health Care Resource Utilization in a Single-payer Public Health
      Care System: Development and Validation of the High Resource User Population Risk
      Tool.
AB  - BACKGROUND: A large proportion of health care spending is incurred by a small
      proportion of the population. Population-based health planning tools that
      consider both the clinical and upstream determinants of high resource users (HRU)
      of the health system are lacking. OBJECTIVE: To develop and validate the High
      Resource User Population Risk Tool (HRUPoRT), a predictive model of adults that
      will become the top 5% of health care users over a 5-year period, based on self
      reported clinical, sociodemographic, and health behavioral predictors in
      population survey data. RESEARCH DESIGN: The HRUPoRT model was developed in a
      prospective cohort design using the combined 2005 and 2007/2008 Canadian
      Community Health Surveys (CCHS) (N=58,617), and validated using the external
      2009/2010 CCHS cohort (N=28,721). Health care utilization for each of the 5 years
      following CCHS interview date were determined by applying a person-centered
      costing algorithm to the linked health administrative databases. Discrimination
      and calibration of the model were assessed using c-statistic and Hosmer-Lemeshow
      (HL) chi statistic. RESULTS: The best prediction model for 5-year transition to
      HRU status included 12 predictors and had good discrimination (c
      statistic=0.8213) and calibration (HL chi=18.71) in the development cohort. The
      model performed similarly in the validation cohort (c-statistic=0.8171; HL
      chi=19.95). The strongest predictors in the HRUPoRT model were age, perceived
      general health, and body mass index. CONCLUSIONS: HRUPoRT can accurately project
      the proportion of individuals in the population that will become a HRU over 5
      years. HRUPoRT can be applied to inform health resource planning and prevention
      strategies at the community level.

PMID- 29189577
TI  - Estimating Associations Between Medical Home Adoption, Utilization, and Quality:
      A Comparison of Evaluation Approaches.
AB  - BACKGROUND: Methodological differences between evaluations of medical home
      adoption might complicate readers' ability to draw conclusions across studies.
      OBJECTIVES: To study whether associations between medical home adoption and
      patient care are affected by methodological choices. DESIGN, SETTING, AND
      SUBJECTS: Among 71 practices participating in the Pennsylvania Chronic Care
      Initiative (a medical home pilot), we estimated cross-sectional and longitudinal
      associations between 4 definitions of "medical home adoption" [National Committee
      on Quality Assurance (NCQA) recognition in year 3, Medical Home Index scores at
      baseline and 3, and within-practice changes in Medical Home Index scores between
      baseline and year 3] and utilization and quality. MEASUREMENTS: Six utilization
      and 6 quality measures. RESULTS: In cross-sectional analyses at year 3, NCQA
      recognition was associated with higher rates of nephropathy monitoring (7.23
      percentage points; confidence interval, 0.45-14.02), breast cancer screening
      (7.48; 2.11-12.86), and colorectal cancer screening (8.43; 2.44-14.42). In
      longitudinal analyses, NCQA recognition was associated with increases in
      hospitalization rates (2.75 per 1000 patient-months; 0.52-4.98). In baseline
      cross-sectional analyses, higher Medical Home Index scores were associated with
      fewer ambulatory care-sensitive hospitalizations (-0.61 per 1000 patient per
      month; -1.11 to -0.11), all-cause emergency department visits (-6.80; -12.28 to 
      1.32), and ambulatory care-sensitive emergency department visits (-5.60; 10.32 to
      -0.88). There were no statistically significant associations between any other
      measure of medical home adoption and quality or utilization. CONCLUSIONS: The
      findings of medical home evaluations are sensitive to methodological choices.
      Meta-analyses, narrative reviews, and other syntheses of medical home studies
      should consider subdividing their findings by analytic approach.

PMID- 29189579
TI  - Physical Demands of Exergaming in Healthy Young Adults.
AB  - Tietjen, AMJ and Devereux, GR. Physical demands of exergaming in healthy young
      adults. J Strength Cond Res XX(X): 000-000, 2017-The efficacy of whole-body
      exergaming (WBE) in healthy young adults remains largely unknown. This study
      aimed to: (a) compare the physical demands of WBE in healthy adults with
      traditional exercise; (b) determine whether the physical demands of WBE were
      reproducible. Twenty-five healthy adults (age: 22.9 +/- 6.4 years; height: 1.7 +/
      0.1 m; mass: 69.1 +/- 12.2 kg) completed two 10-minute experimental conditions
      (WBE on the Xbox Kinect and treadmill walking) in a randomized cross-over design
      study. Whole-body exergaming produced a significant increase in the peak heart
      rate (138 +/- 23 b.min), oxygen consumption (40 +/- 13 ml.kg.min), metabolic
      equivalents (METs) (11 +/- 4) compared with treadmill walking (115 +/- 18 b.min,
      25 +/- 5 ml.kg.min, 7 +/- 2 MET) and a modest increase in the mean heart rate
      (111 +/- 19 b.min vs. 104 +/- 15 b.min). Whole-body exergaming produced
      significantly greater vertical (381 +/- 118 vs. 127 +/- 14 % body weight [%BW]),
      anterior (70 +/- 22 vs. 27 +/- 4 %BW), and medial (56 +/- 21 vs. 7 +/- 2 %BW)
      ground reaction forces. No difference was present in mean oxygen consumption and
      MET. The reproducibility of WBE was assessed in a subgroup of 11 participants
      (age: 24.2 +/- 6.7 years; height: 1.8 +/- 0.1 m; mass: 75.3 +/- 10.0 kg), who
      completed 2 additional 10-minute WBE sessions. No difference was observed between
      all outcome measures. These findings indicate that WBE can reliably replicate, or
      surpass, the physical demands of treadmill walking and may serve as an effective
      addition to a health-focused exercise program.

PMID- 29189578
TI  - Validity of an Isometric Midthigh Pull Dynamometer in Male Youth Athletes.
AB  - Till, K, Morris, R, Stokes, K, Trewartha, G, Twist, C, Dobbin, N, Hunwicks, R,
      and Jones, B. Validity of an isometric midthigh pull dynamometer in male youth
      athletes. J Strength Cond Res 32(2): 490-493, 2018-The purpose of this study was
      to investigate the validity of an isometric midthigh pull dynamometer against a
      criterion measure (i.e., 1,000-Hz force platform) for assessing muscle strength
      in male youth athletes. Twenty-two male adolescent (age 15.3 +/- 0.5 years) rugby
      league players performed 4 isometric midthigh pull efforts (i.e., 2 on the
      dynamometer and 2 on the force platform) separated by 5-minute rest in a
      randomized and counterbalanced order. Mean bias, typical error of estimate (TEE),
      and Pearson correlation coefficient for peak force (PF) and peak force minus body
      weight (PFBW) from the force platform were validated against peak force from the
      dynamometer (DynoPF). When compared with PF and PFBW, mean bias (with 90%
      confidence limits) for DynoPF was very large (-32.4 [-34.2 to -30.6] %) and
      moderate (-10.0 [-12.8 to -7.2] %), respectively. The TEE was moderate for both
      PF (8.1 [6.3-11.2] %) and PFBW (8.9 [7.0-12.4]). Correlations between DynoPF and
      PF (r 0.90 [0.79-0.95]) and PFBW (r 0.90 [0.80-0.95]) were nearly perfect. The
      isometric midthigh pull assessed using a dynamometer underestimated PF and PFBW
      obtained using a criterion force platform. However, strong correlations between
      the dynamometer and force platform suggest that a dynamometer provides an
      appropriate alternative to assess isometric midthigh pull strength when a force
      platform is not available. Therefore, practitioners can use an isometric midthigh
      pull dynamometer to assess strength in the field with youth athletes but should
      be aware that it underestimates peak force.

PMID- 29189580
TI  - Comparison of Body Composition Variables Across a Large Sample of National
      Collegiate Athletic Association Women Athletes From 6 Competitive Sports.
AB  - Fields, JB, Metoyer, CJ, Casey, JC, Esco, MR, Jagim, AR, and Jones, MT.
      Comparison of body composition variables across a large sample of National
      Collegiate Athletic Association women athletes from 6 competitive sports. J
      Strength Cond Res 32(9): 2452-2457, 2018-Body composition (BC) plays a critical
      role in sport performance and athlete health. Body size and BC have been widely
      studied in men's sports, with reported changes observed over time. However, a
      paucity of current data exists in women athletes. The purpose of this descriptive
      study was to measure and compare BC data for collegiate women athletes from 6
      competitive sports. A total of 524 athletes from 2 National Collegiate Athletic
      Association institutions participated: basketball (BB; n = 95), gymnastics (GYM;
      n = 42), lacrosse (LAX; n = 81), rowing (ROW; n = 57), soccer (SOC; n = 188), and
      volleyball (VB; n = 61). Body height (BH) and body mass (BM) were measured using
      a stadiometer and calibrated digital scale, respectively. Body fat percentage
      (BF%), fat mass (FM), and fat-free mass (FFM) were assessed using air
      displacement plethysmography. One-way analysis of variance was used to assess
      differences across sports. Least squares difference post hoc analyses were
      performed when a significant finding (p <= 0.05) was identified. ROW had the
      highest BF% (29.9 +/- 6.1%) and BB the greatest FFM (57.2 +/- 6.1 kg). GYM had
      the lowest BM (58.9 +/- 5.3 kg), FM (11.6 +/- 2.6 kg), and BH (158.73 +/- 2.13
      cm). LAX, SOC, and VB had similar BF%. Body height was greatest for BB and VB
      (177.92 +/- 7.55 cm, 176.79 +/- 7.36 cm, respectively). These data may assist in
      the establishment of descriptive values for use in goal setting and exercise
      programming. The current data demonstrate a trend toward increased body size and
      BC from previous research.

PMID- 29189581
TI  - Impact of 10-Minute Interval Roller Massage on Performance and Active Range of
      Motion.
AB  - Hodgson, DD, Quigley, PJ, Whitten, JHD, Reid, JC, and Behm, DG. Impact of 10
      minute interval roller massage on performance and active range of motion. J
      Strength Cond Res XX(X): 000-000, 2017-Roller massage (RM) has been shown to
      increase range of motion (ROM) without subsequent performance deficits. However,
      prolonged static stretching (SS) can induce performance impairments. The
      objective of this study was to examine the effects of combining SS and RM with
      and without subsequent RM on ROM and neuromuscular performance. Subjects (n = 12)
      participated in 5 sessions: (a) SS only (SS_rest), (b) SS + RM (SS + RM_rest),
      (c) SS with RM at 10 and 20 minutes after stretch (SS_RM), (d) SS + RM with RM at
      10 and 20 minutes after stretch (SS + RM_RM), and (e) control. For the SS
      conditions, the quadriceps and hamstrings received passive SS for 2 * 30 seconds
      each. For the SS + RM conditions, SS was applied to the quadriceps and hamstrings
      for 30 seconds each, and RM was performed for 30 seconds per muscle. SS_RM and SS
      + RM_RM conditions received an additional 30-second RM at 10 and 20 minutes after
      warm-up, whereas sessions without additional RM rested for the same duration.
      Testing measures included hip flexion (HF) and knee flexion (KF) active and
      passive ROM, hurdle jump height and contact time, countermovement jump height,
      and maximal voluntary isometric contraction force. Initial KF and HF ROM
      improvements provided by SS_RM and SS + RM_RM were sustained up to 30 minutes
      after intervention. Furthermore, SS_RM exhibited greater ROM compared with
      sessions lacking additional RM in active and passive HF as well as active and
      passive KF. Similarly, SS + RM_RM elicited greater KF and HF ROM improvements
      than SS_rest. In conclusion, active KF and HF ROM improvements were prolonged by
      additional RM, whereas neuromuscular performance remained relatively unaffected.

PMID- 29189582
TI  - Aerobic Fitness in Top-Class Soccer Referees.
AB  - Castagna, C, Bizzini, M, Araujo Povoas, SC, Schenk, K, Busser, G, and D'Ottavio,
      S. Aerobic fitness in top-class soccer referees. J Strength Cond Res XX(X): 000
      000, 2017-The aim of this study was to examine the aerobic fitness status of top
      class male soccer officials using a cross-sectional design and known population
      group constructs. Fifty-two field referees (FRs, age 38.4 +/- 3.3 years; height
      181 +/- 5.6 cm; body mass 76.8 +/- 6.8 kg; body mass index [BMI] 23.4 +/- 1.7
      kg.m; body fat 20.4 +/- 3.6%; and international refereeing experience 5 +/- 3.5
      years) and 104 assistant referees (ARs, age 37.8 +/- 4.1 years; height 176.9 +/-
      7.5 cm; body mass 72.1 +/- 7.4 kg; BMI 23 +/- 1.6 kg.m; body fat 19.2 +/- 3.6%;
      and international refereeing experience 7 +/- 3.8 years) from 53 National
      Football Associations worldwide, and candidates of the preliminary open-list
      developed by the FIFA Refereeing Department for the 2014 World Cup Final
      Tournament, were tested for aerobic fitness in laboratory conditions with a
      progressive speed treadmill test to exhaustion. Large (+8.54%, d = 0.8) and small
      (+3.1%, d = 0.3) differences in absolute (L.min) and relative (ml.kg.min)
      V[Combining Dot Above]O2max were found between FR and AR, respectively. Trivial
      differences (d = 0.07) were shown in running economy (RE) (6 minutes at 8 km.h)
      between AR and FR. Using the scaling notation (b = 0.64), medium and significant
      differences were found between match officials for V[Combining Dot Above]O2max
      and RE (FR > AR; d = 0.6 and 0.67, respectively). Using receiver operating
      characteristic curve statistics, cutoff values of 3.93 L.min and 50.6 ml.kg.min
      were detected in absolute and relative V[Combining Dot Above]O2max for the FR and
      the AR (FR > AR), respectively. The FR showed superior aerobic fitness compared
      with AR. Training prescription should consider intensities at anaerobic threshold
      speed (14 km.h, 91% heart rate max) when aerobic fitness development is the aim
      in elite officials.

PMID- 29189583
TI  - Modeling Fitness Variable Responses To Training In Prepubescent Children.
AB  - The aim of this study was to determine strength and oxygen uptake (VO2max)
      performances according to different training program intervention design with 8
      weeks duration in prepubescent children through a multiple linear regression
      models. Two hundred and forty-five healthy prepubescent children (aged 10.9 +/-
      0.5 years) were randomly assigned to a specific training program (strength
      training only - S; aerobic training only - A; intra-session aerobic and strength
      training - AS; intra-session strength and aerobic training - SA; or concurrent
      training performed in different sessions - CT) or a control group (no training
      regimen - C). It was possible to develop indirect predictive models for each
      training method, by including each variable pre-training, body fat percentage and
      body mass index. The models provided explained 82% of variance in the VO2max, 98%
      in the 1kg ball-throw, 96% in the 3kg ball-throw, 92% in the counter-movement
      jump, 93% in the standing long jump and 98% in the 20m sprint performances. This
      novel approach to training evaluation and control aims to provide a tool to allow
      professionals to calculate changes with a high confidence level (CI 95%), to
      control gains and to choose the best training methodology to apply according to
      the defined purposes. The results of this study could be a great support to
      teachers, coaches and professionals providing important tools to improve the
      efficacy and individualization of training.

PMID- 29189584
TI  - Body Image Amongst Elite Rugby Union Players.
AB  - There is limited information on the risk of eating disorders and body image of
      elite male athletes. However, research suggests there are some athletes who have
      poor body image and they may be at increased risk of developing eating disorders.
      Therefore, the current study investigated risk of eating disorders, body image,
      and the relationship with age, in elite rugby union players during their pre
      season training period.This cross-sectional study was undertaken at the start of
      the pre-season amongst elite rugby union players in New Zealand. Twenty-six
      professional rugby union players completed a 49-item questionnaire on body image
      and disordered eating. A 'body image score' was calculated from questionnaire
      subscales including 'drive for thinness', 'bulimia' and 'body dissatisfaction',
      with total scores above twenty indicative of poor body image.Body image scores
      varied from 8-39 out of a possible 0-100. Disordered eating behaviours were
      reported, including binge eating at least once a week (15%, n=4/26), pathogenic
      weight control use (4%, n=1/26) and avoidance of certain foods (77%, n=20/26).
      There was a statistically significant inverse association between the bulimia
      subscale and age (P = 0.034).At the start of the pre-season training period, many
      elite rugby union players experience disturbances in body image. The prevalence
      of disordered eating behaviours is of concern, and needs to be minimised due to
      the negative impact on health and performance. A focus on assessment and
      education of younger male rugby players may be required in order to reduce
      disordered eating patterns.

PMID- 29189585
TI  - Muscle Damage and Metabolic Responses to Repeated-Sprint Running With and Without
      Deceleration.
AB  - Minahan, CL, Poke, DP, Morrison, J, and Bellinger, PM. Muscle damage and
      metabolic responses to repeated-sprint running with and without deceleration. J
      Strength Cond Res XX(X): 000-000, 2017-This study aimed to determine whether
      repeated-sprint running with deceleration aggravates markers of muscle damage or
      delays the recovery of performance compared with repeated-sprint running without
      deceleration. Fourteen male team-sport athletes performed 2 randomly ordered
      testing sessions on a nonmotorized treadmill with one session requiring
      participants to decelerate (TMd) within 4 seconds before stopping or immediately
      step to the side of the treadmill belt at the completion of each sprint (TMa).
      Peak and mean velocities, speed decrement, blood lactate concentrations, and
      oxygen uptake were monitored during the repeated-sprint running protocols.
      Countermovement vertical jump (CMJ) performance, perceived muscle soreness, sit
      and-reach flexibility, plasma creatine kinase (CK), lactate dehydrogenase (LDH),
      and myoglobin (Mb) concentrations were quantified immediately before and after
      and 45 minutes, 24 and 48 hours after repeated-sprint running protocols. Although
      muscle damage was indicated by increases in CK, LDH, and Mb (p <= 0.05) in both
      groups, there was no significant effect of condition (TMa vs. TMd) on any of the
      measured performance or physiological variables (p > 0.05). The present study
      indicated that the removal of deceleration from repeated-sprint running on a
      nonmotorized treadmill has no effect on metabolism or performance during or after
      repeated-sprint running or markers of muscle damage.

PMID- 29189586
TI  - Potential Utility of a Loaded Treadmill Protocol for Tactical Athletes.
AB  - Swearingen, JT, Weiss, LW, Smith, WA, Stephenson, MD, and Schilling, BK.
      Potential utility of a loaded treadmill protocol for tactical athletes. J
      Strength Cond Res 32(3): 610-616, 2018-Aerobic capacity is an important variable
      for tactical athletes, with V[Combining Dot Above]O2max being the most direct way
      of estimating it in a laboratory setting. A mode-specific protocol involving
      fixed-weight, torso-borne loads was assessed in the current study. On 4 separate
      days, 15 men (age 22.1 +/- 2.7 years, mass 85.1 +/- 10.6 kg, height 179.0 +/- 7.7
      cm) performed a weighted treadmill walking protocol (2 trials) and a nonweighted
      treadmill running protocol (2 trials). Both the weighted and nonweighted
      protocols were reliable, with intraclass correlation coefficient values of 0.79
      and 0.87, respectively. V[Combining Dot Above]O2peak values from both protocols
      were highly correlated (r = 0.90, p < 0.01). However, V[Combining Dot
      Above]O2peak was higher during the nonweighted protocol (t = 7.547, d = 2.47, p <
      0.01). Work rate was calculated for both the last completed stage and stage
      during which participants reached fatigue. Work rates for both protocols on the
      last completed stage were similar (t = 1.44, d = 0.83, p = 0.17), although the
      work rate for the final attempted stage was greater for the weighted-walking
      protocol (t = 5.85, d = 3.60, p < 0.01). These data suggest a weighted-walking
      V[Combining Dot Above]O2peak that is highly associated with a running V[Combining
      Dot Above]O2peak. This test may be applied to those who routinely perform torso
      borne load carriage, such as tactical athletes. Future weighted-walking protocols
      should seek achieve higher resolution, especially near the end stage of the test
      where subjects reach volitional fatigue. Large increases in work rate may not be
      feasible at the end stages of the test.

PMID- 29189587
TI  - Effect of Cold (14 degrees  C) vs. Ice (5 degrees  C) Water Immersion on Recovery
      From Intermittent Running Exercise.
AB  - Anderson, D, Nunn, J, and Tyler, CJ. Effect of cold (14 degrees  C) vs. ice (5
      degrees  C) water immersion on recovery from intermittent running exercise. J
      Strength Cond Res 32(3): 764-771, 2018-The purpose was to compare 14 degrees  C
      (CWI14 degrees  C) and 5 degrees  C (CWI5 degrees  C) cold water immersion after
      intermittent running. On 3 occasions, 9 male team-sport players undertook 12
      minutes of CWI14 degrees  C, CWI5 degrees  C, or nonimmersed seated recovery
      (CON) after 45 minutes of intermittent running exercise. Maximal cycling
      performance and markers of recovery were measured before and in the 0-72 hours
      after exercise. Peak power output (PPO) was immediately reduced after all
      interventions (d = 1.8). CWI5 degrees  C was more effective at restoring PPO than
      CWI14 degrees  C (d = 0.38) and CON (d = 0.28) 24 hours after exercise, whereas
      both CON (d = 0.20) and CWI5 (d = 0.37) were more effective than CWI14 degrees  C
      after 48 hours. Cold water immersion (CWI) was more effective than CON at
      restoring PPO 72 hours after exercise (d = 0.28-0.30). Mean power output (MPO)
      was higher in CON compared with CWI5 degrees  C (d = 0.30) and CWI14 degrees  C
      (d = 0.21), but there was no difference between CWI5 degrees  C and CWI14 degrees
      C (d = 0.08). CWI5 degrees  C was more effective than CWI14 degrees  C for
      restoring MPO to baseline levels 24 hours (d = 0.28) and 72 hours (d = 0.28)
      after exercise; however, CON was more, or equally, effective as CWI5 degrees  C
      and CWI14 degrees  C throughout. Lactate and creatine kinase concentrations were
      unaffected. Perceived muscle soreness remained elevated in CWI5 and CON
      throughout but was similar to baseline in CWI14 degrees  C after 72 hours. In
      conclusion, repeated bouts of exercise are initially impaired after 5 and 14
      degrees  C CWI, but PPO may be improved 72 hours after exercise. Cold water
      immersion is not recommended for acute recovery based on these data. Athletes and
      coaches should use the time currently allocated to CWI for more effective and
      alternative recovery modalities.

PMID- 29189588
TI  - A randomized phase II study of S-1 versus capecitabine as first-line chemotherapy
      in elderly metastatic gastric cancer patients with or without poor performance
      status: clinical and pharmacogenetic results.
AB  - OBJECTIVE: This study investigated the efficacy and safety of S-1 versus
      capecitabine in elderly patients with metastatic gastric cancer (MGC), and
      examined the association between cytochrome P450 2A6 (CYP2A6) polymorphisms and
      treatment outcomes. MATERIALS AND METHODS: MGC patients 70-85 years old with
      Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or 65-70 years
      old with ECOG PS 2 were randomized to receive S-1 40 mg/m, twice daily, or
      capecitabine 1250 mg/m, twice daily, on days 1-14 every 3 weeks. RESULTS: From
      May 2007 up to July 2010, 107 patients were enrolled. G3/4 neutropenia developed
      in 3.8% of each arm, and the most common G3/4 nonhematological toxicities were
      anorexia and fatigue. Vomiting and tearing were more frequent with S-1 and hand
      foot syndrome with capecitabine. The primary endpoint, the overall response rate,
      was 26.4% (14/53, 95% confidence interval: 14.5-38.3%) in S-1 and 24.1% (13/54,
      95% confidence interval: 12.7-35.5%) in capecitabine, both of which exceeded the
      null hypothesis response rate of 10%. The median time to progression (TTP; 3.2
      vs. 3.4 months, P=0.813) and overall survival (OS; 8.5 vs. 10.3 months, P=0.691)
      were similar in both arms. CYP2A6 polymorphisms were associated with S-1
      efficacy. In the S-1 arm only, patients with CYP2A6 variant/variant alleles had
      worse TTP and OS than those with wild/wild or wild/variant alleles, and in
      multivariate analysis, the CYP2A6 genotype was predictive for TTP and OS.
      CONCLUSION: Both S-1 and capecitabine were active and tolerable for elderly MGC
      patients. The CYP2A6 genotyping might guide treatment selection.

PMID- 29189589
TI  - Pediatric Emergency Research Canada: Origins and Evolution.
AB  - OBJECTIVE: The objective of the study was to describe the origins, growth, and
      progress of a national research network in pediatric emergency medicine. METHODS:
      The success of Pediatric Emergency Research Canada (PERC) is described in terms
      of advancing the pediatric emergency medicine agenda, grant funding, peer
      reviewed publications, mentoring new investigators, and global collaborations.
      RESULTS: Since 1995, clinicians and investigators within PERC have grown the
      network to 15 active tertiary pediatric emergency medicine sites across Canada.
      Investigators have advanced the research agenda in numerous areas, including
      gastroenteritis, bronchiolitis, croup, head injury, asthma, and injury
      management. Since the first PERC Annual Scientific meeting in 2004, the
      attendance has increased by approximately 400% to 152 attendees, 65
      presentations, and 13 project/investigator meetings. More than $33 million in
      grant funding has been awarded to the network, and has published 76 peer-reviewed
      articles. In 2011, PERC's success was recognized with a Top Achievement Award in
      Health Research from Canadian Institutes of Health Research and the Canadian
      Medical Association Journal. CONCLUSIONS: Moving forward, PERC will continue to
      focus on the creation of new knowledge, the mentorship of new investigators and
      fellows in developing research projects, and promoting a pediatric emergency
      medicine-focused research agenda guided by the pooling of expertise from
      individuals across the nation. Through collaborations with networks across the
      globe, PERC will continue to strive for the conduct of high-quality, impactful
      research that improves outcomes in children with acute illness and injury.

PMID- 29189590
TI  - Management of Pediatric Isolated Skull Fractures: A Decision Tree and Cost
      Analysis on Emergency Department Disposition Strategies.
AB  - OBJECTIVE: Pediatric isolated skull fractures (ISFs) are common injuries that
      represent challenging disposition decisions for clinicians. The purpose of this
      study is to use a decision analysis to compare the clinical and cost
      effectiveness of 3 emergency department (ED)-based disposition scenarios for a
      pediatric patient presenting with ISF. METHODS: We conducted a cost-effectiveness
      analysis comparing ED disposition scenarios that included current practice,
      increased at-home surveillance, and observation unit utilization. Current rates
      of admission, deterioration after initial diagnosis, and ED return after
      discharge, as well as cost of observation-only status, were obtained through
      literature review. Cost calculations using Healthcare Cost and Utilization
      Project data included total ED cost, admission without complication, and
      admission with deterioration. RESULTS: In current practice, 76% of subjects with
      ISF are admitted and 2.5% of those develop persistent or new symptoms. No patient
      diagnosed with ISF required neurosurgical intervention. Of those discharged home
      from the ED, 2.8% return with a new concern with 7.4% having new findings on
      imaging leading to admission. Total cost per 100 patients by current practice was
      US $583,587. Increasing at-home surveillance by 20% resulted in a total cost
      saving of US $113,176 per 100 patients while increasing returns to the ED from
      less than 1% to 1.1%. Admitting at the current rate to an observation unit
      resulted in a US $205,395 cost saving per 100 patients. CONCLUSIONS: Decreased
      inpatient utilization through home surveillance or observation unit use reduced
      cost associated with pediatric ISF management without increasing clinical risk
      owing to the low probability of clinical deterioration after initial diagnosis.

PMID- 29189591
TI  - Luc's Abscess and Temporomandibular Joint Septic Arthritis: Two Rare Sequelae of
      Acute Otitis Media.
AB  - A 5-year-old previously healthy child presented with right-sided otalgia, right
      facial and temporal swelling, and right jaw pain in the setting of 6 days of low
      grade fever. The child had no trauma, vomiting, or prior dental treatments. On
      physical examination, the patient had facial swelling, erythema, and tenderness
      over the right temporal region along with trismus, as well as pain on palpation
      of the right temporomandibular joint (TMJ). A computed tomography scan revealed
      otitis media, Luc's abscess, and TMJ septic arthritis requiring surgical drainage
      and intravenous antibiotics. The patient responded well to treatment and
      recovered without sequelae. Dr. Cardwell Luc first described Luc's abscess in
      1913 as a rare complication of middle ear infection leading to an abscess in the
      infratemporal space. To our knowledge, our case is the first documented case of
      concurrent Luc's abscess and TMJ septic arthritis in a previously healthy child
      as complications of acute otitis media. This case highlights 2 rare complications
      of a common medical condition that pediatric emergency care providers should
      recognize due to the need for surgical intervention, without which there may be
      longstanding sequelae.

PMID- 29189592
TI  - Early Reduction of Pediatric Traumatic Posterior Hip Dislocation Is Much More
      Important Than the Treatment Procedure.
AB  - Traumatic hip dislocations are very rare in the pediatric population, and they
      are real emergent cases that can occur with minimal trauma. If they are not
      diagnosed immediately and reduction is not performed as soon as possible, they
      may cause problems such as avascular necrosis and degenerative arthritis.
      Performing reduction within the first 6 hours is of vital importance.We aim to
      present the functional outcomes and radiographic results of 2 pediatric traumatic
      hip dislocation cases with 36 months of follow-up who were treated with abduction
      orthosis after the reduction. We want to emphasize the importance of reduction
      time in the outcome of posterior traumatic hip dislocations followed with
      abduction orthesis even if there is a trend and suggestion to treat these
      patients with spica cast with the review of the recent literature.

PMID- 29189593
TI  - Association of Insurance With Use of Emergency Medical Services Among Children.
AB  - OBJECTIVE: The use of emergency medical services (EMS) can be lifesaving for
      critically ill children and should be defined by the child's clinical need. Our
      objective was to determine whether nonclinical demographic factors and insurance
      status are associated with EMS use among children presenting to the emergency
      department (ED). METHODS: In this cross-sectional study using the National
      Hospital Ambulatory Medical Care Survey, we included children presenting to EDs
      from 2009 to 2014. We evaluated the association between EMS use and patients'
      insurance status using multivariable logistic regressions, adjusting for
      demographic, socioeconomic, and clinical factors such as illness severity as
      measured by a modified and recalibrated version of the Revised Pediatric
      Emergency Assessment Tool (mRePEAT) and the presence of comorbidities or chronic
      conditions. A propensity score analysis was performed to validate our findings.
      RESULTS: Of the estimated 191,299,454 children presenting to EDs, 11,178,576
      (5.8%) arrived by EMS and 171,145,895 (89.5%) arrived by other means. Children
      arriving by EMS were more ill [mRePEAT score, 1.13; 95% confidence interval (CI),
      1.12-1.14 vs mRePEAT score, 1.01; 95% CI: 1.01-1.02] and more likely to have a
      comorbidity or chronic condition (OR: 3.17, 95% CI: 2.80-3.59). In the adjusted
      analyses, the odds of EMS use were higher for uninsured children and lower for
      children with public insurance compared with children with private insurance [OR
      (95% CI): uninsured, 1.41 (1.12-1.78); public, 0.77 (0.65-0.90)]. The propensity
      score analysis showed similar results. CONCLUSIONS: In contrast to adult
      patients, children with public insurance are less likely to use EMS than children
      with private insurance, even after adjustment for illness severity and other
      confounders.

PMID- 29189594
TI  - Unusual Case of Penile Ecchymosis.
AB  - Hirudin is a potent anticoagulant found in the salivary glands of several species
      of leeches. We report a case of direct hirudin exposure after suspected leech
      bite causing significant penile ecchymosis. Diagnosis was not apparent on initial
      evaluation but made after a thorough history was obtained and the leech was found
      in the lining of his swim trunks, which he left at home. Although this
      presentation mimics several other potentially serious conditions, treatment is
      largely observational with anticipated rapid improvement over the course of hours
      without intervention.

PMID- 29189595
TI  - Fast and Sensitive: Automated Point-of-Care Urine Dips.
AB  - OBJECTIVE: Point-of-care (POC) urine dipstick is a highly used test in the
      pediatric emergency department (PED) owing to its fast turn-around time and
      inexpensive cost. Past studies have shown hand-held urine dipsticks and automated
      urinalysis in children younger than 48 months to be sensitive predictors for
      urinary tract infection (UTI). It is hypothesized that POC dip testing is as
      accurate as laboratory urinalysis in the diagnosis of UTI. METHODS: A
      retrospective chart review was conducted on patients (aged birth through 18
      years) presenting to a PED between January 2015 and December 2015. Eligible
      subjects included those that had a POC dip, laboratory urinalysis (lab UA), and
      urine culture performed during their PED visit. Subjects were selected, using a
      random number generator; 334 charts were selected. A positive POC dip was defined
      as having a positive leukocyte esterase or the presence of nitrites. A positive
      lab UA was defined as having a positive leukocyte esterase, nitrites, or greater
      than 10 white blood cells per high-power field. Urine culture was used as the
      criterion standard for comparison. RESULTS: A total of 334 subjects' charts were
      reviewed. Sensitivity and specificity of the POC dip were 91.4% (95% confidence
      interval [CI], 76.9%-98.2%) and 63.9% (95% CI, 57.2%-69.3%); lab UA, 91.4% (95%
      CI, 76.9%-98.2%) and 63.9% (95% CI, 58.2%-69.3%); and lab dip, 88.6% (95% CI,
      73.3%-96.8%) and 65.6% (95% CI, 59.9%-70.9%). CONCLUSIONS: Point-of-care dips are
      as sensitive in detecting UTI as the lab UA. A prospective study could allow for
      further demographic evaluation of POC dip diagnosed UTI.

PMID- 29189596
TI  - Procedural Training and Assessment for Pediatric Emergency Medicine Physicians
      Within the United States and Canada: A Survey Study.
AB  - OBJECTIVES: The aims of this study were to determine current practices in
      procedural training and skill assessment for attending physicians working in
      pediatric emergency departments within the United States and Canada and identify
      barriers to providing training and assessment. METHODS: This was a cross
      sectional survey study. Members of the pediatric emergency medicine fellowship
      program directors and associate program directors Listserv were invited to
      participate in an anonymous survey about attending physician training and
      assessment practices for 9 specific procedures and barriers to training and
      assessment. RESULTS: Eighty-two (56.2%) of 146 recipients responded, with 79
      surveys fully completed; 58.5% of responders report that their division offers
      procedural training, whereas 14.6% report assessment of procedural skills. The
      most common procedure for which participants report training and assessment is
      orotracheal intubation (53.1% and 7.5%, respectively), with training rates for
      other procedures ranging from 2.5% to 43.0%. Most sites that report training use
      simulation in some form for education. For assessment, simulation is used almost
      exclusively. Cost (50.6%), lack of faculty interest (36.7%), and lack of
      standardized guidelines (36.7%) are the most common barriers to training. Lack of
      standardized guidelines (51.9%), cost (43.0%), and lack of faculty interest
      (38.0%) are the most common barriers for assessment. CONCLUSIONS: Although
      pediatric emergency medicine physicians may be required to perform emergent
      procedures, opportunities to receive training and assessment in these procedures
      are limited. Simulation and other educational modalities are being used to
      provide skill training and assessment, but cost and lack of resources,
      standardized protocols, and faculty interest are barriers to the implementation
      of training and assessment programs.

PMID- 29189597
TI  - Ultrasonic Percutaneous Tenotomy of Common Extensor Tendons for Recalcitrant
      Lateral Epicondylitis.
AB  - Tennis elbow is a common musculoskeletal condition affecting middle-aged patients
      with symptoms usually lasting from 6 months to 2 years. The vast majority of
      individuals will respond to conservative therapy; however, some will require
      surgical intervention. A new treatment system has been developed for use with
      ultrasound guidance in the ultrasonic microresection of tendinopathic tissue.
      This technology has been implemented in the TX1 Tissue Removal System and is used
      to treat various tendinopathies by debridement using targeted ultrasonic energy.
      We describe the surgical technique for the TX1 system as well as provide pain and
      functional outcome scores for a series of patients with recalcitrant lateral
      epicondylitis treated with percutaneous tenotomy with ultrasonic energy utilizing
      ultrasound guidance.

PMID- 29189598
TI  - Comparison of Psychiatric Symptoms in Patients With Obstructive Sleep Apnea,
      Simple Snoring, and Normal Controls.
AB  - OBJECTIVE: Patients with sleep-related breathing disorders are known to have more
      severe psychiatric symptoms than good sleepers. The aim of this study was to
      compare the psychiatric symptoms of participants with obstructive sleep apnea
      (OSA), those with simple snoring (SS), and normal controls (NC). METHODS: A total
      of 386 participants (260 with OSA, 75 with SS, and 51 NC) completed self-report
      questionnaires including the Symptoms Checklist 90-Revised and underwent
      nocturnal polysomnography. The scores of nine primary symptom dimensions and
      three global distress indices of the Symptoms Checklist 90-Revised were compared
      among the three groups, adjusting for age, sex, and body mass index. RESULTS:
      Participants with suspected OSA (OSA + SS) reported more severe psychiatric
      symptoms than the NC group. Compared with the participants with OSA, those with
      SS manifested more severe obsessive-compulsive (1.4 (1.0) versus 1.1 (0.7), p =
      .008) and depressive (1.2 (1.2) versus 0.8 (0.8), p = .031) symptoms and higher
      Global Severity Index (1.0 (0.9) versus 0.7 (0.6), p = .039) and Positive Symptom
      Distress Index (2.0 (0.8) versus 1.7 (0.6), p = .009). Only higher Pittsburgh
      Sleep Quality Index values predicted higher Global Severity Index (B = 0.11, p =
      .041) and Positive Symptom Distress Index (B = 0.46, p = .007) in suspected OSA
      participants. CONCLUSIONS: This study found that individuals with suspected OSA
      experienced more severe psychiatric symptoms than NCs and that psychiatric
      symptoms were more severe in the SS group than in the OSA group. The psychiatric
      symptoms of suspected OSA patients were associated with subjective sleep quality
      rather than with the apnea-hypopnea index.

PMID- 29189599
TI  - Local estrogen benefits of postmenopausal women with dyspareunia: data confirming
      what clinicians already know!

PMID- 29189600
TI  - Pharmacoeconomic and associated cost savings among women who were prescribed
      systemic conjugated estrogens therapy compared with those without menopausal
      therapy.
AB  - OBJECTIVE: To explore changes in healthcare costs among postmenopausal women in a
      commercial population who were prescribed conjugated estrogens for menopausal
      symptoms. METHODS: Using the MarketScan dataset from April 1, 2008 through
      September 30, 2012, postmenopausal women aged >=45 years, who were prescribed
      conjugated estrogen tablets (Premarin), were identified. A comparative cohort of
      postmenopausal women with vasomotor symptoms without any menopause therapy was
      also identified. Women included were required to have continuous medical and
      pharmacy benefits for 6 months before and 12 months after index date, with
      baseline characteristics compared using chi-square and t tests. The 6 and 12
      month change (difference in follow-up and baseline costs) in direct healthcare
      costs was calculated and a difference-in-differences model was used to compare
      the incremental change at 6 and 12 months in healthcare costs between the
      cohorts, adjusting for demographic and clinical characteristics. RESULTS: The
      study included 1,404 women who were prescribed conjugated estrogens, and 3,096
      untreated women. Women prescribed conjugated estrogens were significantly younger
      (52 vs 54 years; P < 0.0001) and had a lower Charlson comorbidity index score
      (0.29 vs 0.41; P < 0.001) compared with the untreated women. After adjusting for
      baseline characteristics, women treated with conjugated estrogens showed a
      greater difference in the change in total healthcare costs (-$1,601 vs -$503; P =
      0.044), including inpatient stay costs (-$1,431 vs -$28; P < 0.0001), between the
      baseline and follow-up periods compared with untreated women. CONCLUSIONS: Women
      who were prescribed oral conjugated estrogens had a significantly greater
      reduction in healthcare costs after treatment initiation compared with untreated
      postmenopausal women.

PMID- 29189601
TI  - More evidence why the product labeling for low-dose vaginal estrogen should be
      changed?

PMID- 29189602
TI  - The history and basic science development of soy isoflavones.
AB  - This review summarizes the 2016 NAMS/Pfizer-Wulf H. Utian Endowed Lecture that
      focused on the history and basic science of soy isoflavones. Described is a
      personal perspective of the background and history that led to the current
      interest in soy and isoflavones with a specific focus on the role that soy
      isoflavones play in the health of postmenopausal women. This overview covers the
      metabolism and physiological behavior of isoflavones, their biological properties
      that are of potential relevance to aging, issues related to the safety of soy
      isoflavones, and the role of the important intestinally derived metabolite S-(
      )equol.

PMID- 29189604
TI  - 2017 Military Supplement to Shock Journal PerftoranTM (VidaphorTM) - Introduction
      to Western Medicine.
AB  - Perftoran, which has been re-branded as Vidaphorfor marketing in North America,
      is an emulsion of perfluorocarbons in a surfactant and electrolyte mixture. It
      was developed in Russia as an oxygen-carrying intravenous plasma additive for
      hemorrhagic anemia and ischemic conditions from various etiologies. It was
      approved for clinical use in Russia in 1996 and used by the Russian Armed Forces
      and in civilian medical care. It was also approved in Mexico from 2005 to 2010.
      It has been reportedly administered to over 35,000 patients with significant
      evidence of benefit and relatively mild and manageable adverse effects. It may
      have significant potential for use in hemorrhagic shock if human red blood cells
      are not available, and for several other applications including treatment of
      vascular gas embolism, cerebral or spinal trauma, and regional ischemia. It is
      different from other perfluorocarbon preparations under development in the USA in
      that is uses a different primary perfluorocarbon (perfluorodecalin) and a
      surfactant (Proxanol 268) instead of egg-yok phospholipid as the emulsion
      vehicle. Perftoran has a much smaller particle size resulting in milder adverse
      effects. It has been safely administered to more patients than any oxygen carrier
      currently under development. A newly formed United States Corporation (FluorO2
      Therapeutics, Inc.) intends to manufacture the product in the United States under
      GMP standards and make it available for clinical use in Mexico and Latin America
      and pursue research to support eventual approval in the USA for human and
      veterinary use. This article will briefly review key information about this
      product and provide references for the interested reader.

PMID- 29189603
TI  - The dynamics of stress and fatigue across menopause: attractors, coupling, and
      resilience.
AB  - OBJECTIVE: The objective of this study was to evaluate the regulatory dynamics
      between stress and fatigue experienced by women during the menopausal transition
      (MT) and early postmenopause (EPM). Fatigue and perceived stress are commonly
      experienced by women during the MT and EPM. We sought to discover relationships
      between these symptoms and to employ these symptoms as possible markers for
      resilience. METHODS: Participants were drawn from the longitudinal Seattle
      Midlife Women's Health Study. Eligible women completed questionnaires on 60+
      occasions (annual health reports and monthly health diaries) (n = 56 women). The
      total number of observations across the sample was 4,224. STRAW+10 criteria were
      used to stage women in either in late reproductive, early or late transition, or
      EPM stage. Change values were generated for fatigue and stress and analyzed with
      a multilevel structural equation model; slopes indicate how quickly a person
      returns to homeostasis after a perturbation. Coupling of stress and fatigue was
      modeled to evaluate resilience, the notion of maintaining stability during
      change. RESULTS: Eligible women were on average 35 years old (SD = 4.71), well
      educated, employed, married or partnered, and white. Fit indices suggested the
      model depicts the relationships of stress and fatigue (chi(9 df) = 7.638, P =
      0.57, correction factor = 4.9244; root mean square error of approximation (RMSEA)
      90% CI = 0.000 <= 0.000 <= 0.032; comparative fit index (CFI) = 1.00). A loss in
      model fit across stages suggests that the four stages differed in their dynamics
      (chiDelta(12 df) = 21.181, P = .048). All stages showed fixed-point attractor
      dynamics: fatigue became less stable over time; stress generally became more
      stable over time. Coupling relationships of stress on fatigue show evidence for
      shifts in regulatory relationships with one another across the MT. CONCLUSIONS:
      Results are suggestive of general dysregulation via disruptions to coupling
      relationships of stress and fatigue across the MT. Findings support a holistic
      approach to understanding symptoms and supporting women during the MT.

PMID- 29189605
TI  - Involvement of Aromatic Metabolites in the Pathogenesis of Septic Shock.
AB  - INTRODUCTION: We hypothesized that aromatic microbial metabolites (AMM), such as
      phenyllactic (PhLA), p-hydroxyphenylacetic (p-HPhAA), and p-hydroxyphenyllactic
      (p-HPhLA) acids, contribute to the pathogenesis of septic shock. METHODS:
      Clinical and laboratory data of patients with community-acquired pneumonia were
      obtained on intensive care unit admission and the next day. Patients were divided
      into two groups based on septic shock presence or absence. The levels of AMM
      (PhLA, p-HPhAA, p-HPhLA, and their sum, ?3AMM), catecholamine metabolites (3,4
      dihydroxymandelic [DHMA], 3,4-dihydroxyphenylacetic [DOPAC], and homovanillic
      [HVA] acids), lactate, N-terminal pro-brain natriuretic peptide (NT-proBNP),
      inducible nitric oxide synthase (iNOS), and procalcitonin (PCT) were compared.
      Correlations between AMM and clinical and laboratory data were calculated.
      RESULTS: There were 20 patients in the septic shock group and 21 in the nonseptic
      shock group. On admission, the septic shock patients demonstrated significantly
      higher levels of PhLA (2.3 vs. 0.8 MUmol/L), p-HPhAA (4.6 vs. 1.4 MUmol/L), p
      HPhLA (7.4 vs. 2.6 MUmol/L), HVA, lactate, and significantly lower levels of
      iNOS. The next day, the two groups also showed significant differences in the
      levels of PCT and NT-proBNP. The correlation between ?3AMM and presence of shock,
      levels of lactate, HVA, and NT-proBNP on admission was 0.44, 0.67, 0.57, and
      0.38, respectively, and the correlation on the next day was 0.59, 0.73, 0.76, and
      0.6, respectively (P < 0.01). These findings can be explained by the ability of
      AMM to reduce tyrosine hydroxylase activity, thus limiting the synthesis of
      catecholamines. CONCLUSIONS: AMM are involved in the pathogenesis of septic
      shock.

PMID- 29189606
TI  - Moyamoya Syndrome in a Child With HIV-1 Infection.
AB  - Neurologic manifestations of HIV infection are not uncommon. However, stroke
      secondary to Moyamoya syndrome has rarely been described in children with HIV
      infection. We report a 10-year-old boy with perinatally acquired HIV-1 infection,
      who presented with recurrent strokes while on antiretroviral therapy.

PMID- 29189607
TI  - Effect of Oral Probiotic Streptococcus salivarius K12 on Group A Streptococcus
      Pharyngitis: A Pragmatic Trial in Schools.
AB  - BACKGROUND: The aim of this study was to examine effectiveness of oral probiotic
      Streptococcus salivarius K12 in preventing group A streptococcus pharyngitis in 5
      to 14-year-old children at high risk of acute rheumatic fever. New Zealand has
      high rates of acute rheumatic fever among Maori and Pacific children. Children
      were already enrolled in a school-based Ministry of Health throat swabbing and
      treatment program. Children self-identified and reported sore throats daily and
      were swabbed twice weekly. METHODS: A total of 1314 children were quasirandomized
      (based on odd or even birthdates) to receive either K12 (2.5 * 10 cfu per
      lozenge) or placebo lozenges and continued observed daily treatment (in the
      school week, during school time) for one school year. RESULTS: A total of 801
      children (61.0%) reported a sore throat on one or more occasions resulting in
      2927 pharyngeal swabs. Of these swabs, 1525 (52.1%) were taken from 411 children
      receiving K12 and 119 (7.8%) of these were positive for group A streptococcus on
      routine culture. In addition, 1402 (47.8%) swabs were taken from 390 children
      receiving placebo and 124 (8.8%) were positive. Overall there was a
      nonsignificant 11.2% relative reduction in positive swabs among children
      receiving K12. This relative reduction was greater for older children, 7-9 years
      of age, 15.6%, and for children 10 years and older, 30.2%. CONCLUSIONS: S.
      salivarius K12 had modest nonsignificant effects on culture-positive sore throats
      when given at school, during the school day. Based on our pragmatic trial, the
      routine use of this probiotic in the prevention of pharyngitis associated with
      GAS detection is not supported.

PMID- 29189608
TI  - Race, Income and Insurance Status Affect Neonatal Sepsis Mortality and Healthcare
      Resource Utilization.
AB  - BACKGROUND: Socioeconomic disparities negatively impact neonatal health. The
      influence of sociodemographic disparities on neonatal sepsis is understudied. We
      examined the association of insurance payer status, income, race and gender on
      neonatal sepsis mortality and healthcare resource utilization. METHODS: We used
      the Kid's Inpatient Database, a nationwide population-based survey from 2006,
      2009 and 2012. Neonates diagnosed with sepsis were included in the study.
      Multivariable logistic regression (mortality) and multivariable linear regression
      (length of stay and total hospital costs) were constructed to determine the
      association of patient and hospital characteristics. RESULTS: Our study cohort
      included a weighted sample of 160,677 septic neonates. Several sociodemographic
      disparities significantly increased mortality. Self-pay patients had increased
      mortality (odds ratio 3.26 [95% confidence interval: 2.60-4.08]), decreased
      length of stay (-2.49 +/- 0.31 days, P < 0.0001) and total cost (-$5015.50 +/-
      783.15, P < 0.0001) compared with privately insured neonates. Additionally, low
      household income increased odds of death compared with the most affluent
      households (odds ratio 1.19 [95% confidence interval: 1.05-1.35]). Moreover,
      Black neonates had significantly decreased length of stay (-0.86 +/- 0.25, P =
      0.0005) compared with White neonates. CONCLUSIONS: This study identified specific
      socioeconomic disparities that increased odds of death and increased healthcare
      resource utilization. Moreover, this study provides specific societal targets to
      address to reduce neonatal sepsis mortality in the United States.

PMID- 29189610
TI  - Early Childhood Neurodevelopmental Outcomes in Infants Exposed to Infectious
      Syphilis In Utero.
AB  - BACKGROUND: There are minimal neurodevelopmental follow-up data for infants
      exposed to syphilis in utero. METHODS: This is an inception cohort study of
      infants exposed to syphilis in utero. We reviewed women with reactive syphilis
      serology in pregnancy or at delivery in Edmonton (Canada), 2002 through 2010 and
      describe the neurodevelopmental outcomes of children with and without congenital
      syphilis. RESULTS: There were 39 births to women with reactive syphilis serology,
      9 of whom had late latent syphilis (n = 4), stillbirths (n = 2) or early neonatal
      deaths (n = 3), leaving 30 survivors of which 11 with and 7 without congenital
      syphilis had neurodevelopmental assessment. Those with congenital syphilis were
      all born to women with inadequate syphilis treatment before delivery.
      Neurodevelopmental impairment was documented in 3 of 11 (27%) infants with
      congenital syphilis and one of 7 (14%) without congenital syphilis with speech
      language delays in 4 of 11 (36%) with congenital syphilis and 3 of 7 (42%)
      without congenital syphilis. CONCLUSIONS: Infants born to mothers with reactive
      syphilis serology during pregnancy are at high risk for neurodevelopmental
      impairment, whether or not they have congenital syphilis, so should all be
      offered neurodevelopmental assessments and early referral for services as
      required.

PMID- 29189609
TI  - Introduction of Routine HIV Birth Testing in the South African National
      Consolidated Guidelines.
AB  - BACKGROUND: South Africa represents the first high-burden setting to introduce
      routine virologic testing at birth within its early infant diagnosis program,
      implemented in June 2015. National HIV birth testing coverage, intrauterine
      transmission rates and case rates for the first year since introduction of
      universal birth testing are reported. METHODS: HIV polymerase chain reaction
      (PCR) test data from June 2015 to May 2016 were extracted from the National
      Health Laboratory Service's central data repository by year, month, age, result
      and geographic location. Birth testing was defined as all HIV PCR tests performed
      at <7 days of life; coverage as the proportion of all HIV-exposed neonates born
      who were tested at birth; estimated intrauterine transmission rate as the
      percentage of HIV PCR positive tests in HIV-exposed neonates tested and case
      rates as the number of HIV PCR positive tests per 100,000 total live births.
      RESULTS: Between June 2015 and May 2016, the South African national monthly birth
      testing coverage increased from 39% (8636 tests) to 93% (20,479 tests). During
      this period, the number of positive tests at birth increased from 114 to 234 per
      month, equating to a national intrauterine transmission rate of 1.1% and a birth
      case rate of 247 per 100,000 live births. CONCLUSIONS: Universal birth testing
      for all HIV-exposed neonates is rapidly being achieved in South Africa,
      facilitating earlier detection of intrauterine infected neonates. However, the
      successful linkage into care of HIV-infected neonates and their treatment
      outcomes remain to be assessed.

PMID- 29189611
TI  - Treatment of Acute Otitis Media in the Pediatric Emergency Department.
AB  - BACKGROUND: Over-treatment of acute otitis media (AOM) with antibiotics is
      common, and poses a high burden on health-care systems. METHODS: Records of
      children 6-36 months of age with AOM visiting a university-affiliated pediatric
      emergency department between 2014 and 2016 were reviewed for the treatment given:
      watchful waiting versus antibiotics. If antibiotics were prescribed, the type and
      duration were recorded. We evaluated appropriate and inappropriate treatment
      rates of eligible AOM cases, in respect to the local guidelines, which encourage
      watchful waiting in most mild-moderate cases. RESULTS: Out of 1493 AOM visits,
      863 (57.8%) were boys, with a median age of 14.9 months (interquartile range, 9
      19). The overall pre-visit antibiotic rate was 24.1%, but among those children
      examined by a physician, this rate was 95.2%. Amoxicillin was the most common
      antibiotic, administered in 66.3% of the cases. Only 21 children (5.8%) had been
      treated with antibiotics for >=7 days before their visit, and were considered as
      treatment failure. Antibiotic therapy upon discharge was recorded in 1394/1449
      visits (96.2%), again with amoxicillin as the most common antibiotic therapy, in
      80.8% of the cases. In these visits, the average duration of antibiotic treatment
      was 8.29 days. Appropriateness of treatment (watchful waiting or antibiotics)
      could be analyzed in 1134 visits; 20.9% were considered as inappropriate. Of
      them, 98.3% were prescribed with the wrong antibiotic type and duration.
      CONCLUSIONS: Adherence rate to the local guidelines treatment recommendations for
      uncomplicated AOM was high, as measured by whether appropriate treatment was
      given and type and duration of antibiotics.

PMID- 29189613
TI  - Is There a Need for a Stand-alone Acellular Pertussis Vaccine?

PMID- 29189612
TI  - Evaluation of the Influence of Gastrointestinal Coinfections on Rotavirus Vaccine
      Effectiveness in Botswana.
AB  - BACKGROUND: Studies have demonstrated reduced rotavirus vaccine effectiveness
      (VE) in resource-limited settings. Enteropathogen coinfections in rotavirus cases
      have been hypothesized to contribute to the lower VE in such settings. We sought
      to determine if coinfections affect rotavirus VE in Botswana. METHODS: Between
      June 2013 and April 2015, children <60 months old, presenting with severe
      gastroenteritis at 4 hospitals as part of a national rotavirus surveillance were
      enrolled. Rotavirus enzyme immunoassay (EIA)-positive samples were tested with an
      in-house real-time polymerase chain reaction (PCR) panel that detected 9
      pathogens and a commercial 15 multiplex PCR gastrointestinal pathogen panel.
      Coinfection was defined as detection of rotavirus plus 1 of the 5 pathogens with
      the highest attributable fractions for diarrhea. Vaccine status was compared
      between rotavirus case patients and non-rotavirus "test-negative" controls. VE
      was also calculated restricting cases to those with rotavirus as the only
      pathogen detected. RESULTS: Two hundred and forty-two children tested rotavirus
      EIA positive, and 368 children were negative. Of the 182 rotavirus EIA-positive
      samples tested with the gastrointestinal pathogen panel assay, coinfections were
      detected in 60 (33%). The overall adjusted 2-dose VE was 59% (95% confidence
      interval [CI]: 27-77) in the rotavirus coinfection group and 51% (95% CI: -14 to
      79) in the rotavirus monoinfection subgroup. Using in-house multiplex PCR panel,
      of 213 rotavirus EIA-positive subjects, coinfections were detected in 98 samples
      (46%). The overall adjusted VEs for 2 doses were 48% (95% CI: -2 to 74) and 62%
      (95% CI: 25-80) in rotavirus monoinfection subgroup. CONCLUSIONS: We could not
      find evidence of an effect of enteric coinfections on the effectiveness of
      rotavirus vaccine.

PMID- 29189614
TI  - Acquired Infection and Antimicrobial Utilization During Initial NICU
      Hospitalization in Infants With Congenital Diaphragmatic Hernia.
AB  - BACKGROUND: In addition to substantial medical and surgical intervention,
      neonates with congenital diaphragmatic hernia often have concurrent concerns for
      acquired infection. However, few studies focus on infection and corresponding
      antimicrobial utilization in this population. METHODS: The Children's Hospital
      Neonatal Database was queried for congenital diaphragmatic hernia infants
      hospitalized from January 2010 to February 2016. Patient charts were linked to
      the Pediatric Health Information Systems database. Descriptive clinical data
      including delivery history, cultures sent, diagnosed infection, antimicrobial use
      and outcomes were reported. RESULTS: A total of 1085 unique patients were
      identified after data linkages; 275 (25.3%) were born at <37 weeks' gestation.
      Bacteremia at delivery (2/1085) and in the first 7 days of life (8/1085) was less
      common than later infection, but 976 patients (89.9%) were treated with
      antibiotics. Median number of days on antibiotics was 6 [3,11] for those without
      a documented infection and 21 [13,36] for those with positive cultures. Incidence
      of urinary tract infection, bacteremia and pneumonia increased significantly over
      time and was most common after 28 days. Antibiotic use, conversely, decreased
      over time (92% of infants in week 1 to 44% in week 4 and beyond). CONCLUSIONS:
      Although culture positivity increased with age, risk of these selected infections
      was relatively low for a population in neonatal intensive care unit. An important
      mismatch is observed between culture negativity and high rates of antibiotic
      utilization. These data identify opportunities for antibiotic stewardship quality
      improvement programs.

PMID- 29189615
TI  - Multimodal Treatment of Rhinocerebral Mucormycosis in a Pediatric Patient With
      Relapsed Pre-B Acute Lymphoblastic Leukemia.
AB  - A 17-year-old girl developed invasive rhinocerebral mucormycosis during intensive
      re-induction chemotherapy for relapsed pre-B acute lymphoblastic leukemia. Due to
      the high case fatality rate for invasive mucormycosis in profoundly
      immunosuppressed patients, an aggressive treatment regimen was pursued. In
      addition to the standard of care treatments with intravenous amphotericin and
      aggressive surgical debridements, she received intraventricular amphotericin to
      the brain via an Ommaya reservoir, hyperbaric oxygen treatments, filgrastim,
      intravenous immunoglobulin and antifungal in vitro synergy testing to allow for
      more targeted antifungal therapy with the addition of micafungin. After a 3-month
      treatment course, it was determined that her mucormycosis was under appropriate
      control, allowing her to continue treatment for her leukemia with hematopoietic
      stem cell transplant with a plan for continued intravenous antifungal therapy
      through engraftment.

PMID- 29189616
TI  - Time, Treasure, and Talent-The Season of Giving.

PMID- 29189617
TI  - What's the Benefit of Certification?

PMID- 29189618
TI  - Bilateral Patellar Tendon Rupture.
AB  - The knee is the most complex and largest joint in the body. Injuries to any part
      of this joint affect the entire body. There are multiple injuries that can occur
      to the knee, with the most common being ligament and meniscus tears. A not-so
      common injury to the knee is a patellar tendon rupture. A bilateral patellar
      tendon rupture is extremely rare. A case study of a 43-year-old man who sustained
      a bilateral patellar tendon rupture while playing softball is used to present
      this devastating injury. This discussion includes the incidence and diagnosis of
      the tear, surgical repair, as well as a description of the comprehensive
      rehabilitation process necessary to allow the patient to return to normal
      physical activity. Risks and complications of this surgery and the expected
      outcomes are also presented.

PMID- 29189619
TI  - Bilateral Patellar Tendon Rupture.

PMID- 29189620
TI  - Nurse Practitioner Fracture Liaison Role: A Concept Analysis.
AB  - BACKGROUND: With the worldwide growing aging population, the high prevalence of
      osteoporosis-related fractures is associated with high morbidity and mortality.
      Healthcare costs for treating fractures and subsequent complications will
      increase to $25 billion by 2025. PURPOSE: This article articulates a
      comprehensive concept analysis of the nurse practitioner fracture liaison (NPFL)
      role to provide new insights into the role of nurse practitioner in osteoporosis
      care coordination. METHODS: Walker and Avant's concept analysis framework was
      used to identify the attributes, antecedents, consequences, and empirical
      referents of the NPFL role. Model cases illustrated real-life examples of the
      NPFL role. CONCLUSION: The impact of NPFL role is rather novel in promoting
      healthy bone living at local, national, and international communities. Linking
      the refined outcome of the concept analysis of the NPFL role to osteoporosis care
      helps close osteoporosis care gaps, improve healthcare outcomes, and alleviate
      financial burden by reducing secondary fracture and complications.

PMID- 29189622
TI  - Predictors of Nurses' Intentions to Administer As-Needed Opioid Analgesics for
      Pain Relief to Postoperative Orthopedic Patients in the Acute Care Setting.

PMID- 29189621
TI  - Predictors of Nurses' Intentions to Administer As-Needed Opioid Analgesics for
      Pain Relief to Postoperative Orthopaedic Patients in the Acute Care Setting.
AB  - BACKGROUND: Patients undergoing orthopaedic surgery experience severe
      postoperative pain that is frequently undertreated. No study was found that
      examined the predictors of nurses' intentions to administer as needed (PRN)
      opioid analgesics for postoperative pain relief. PURPOSE: The purpose of this
      study was to determine what constructs from the Integrated Behavioral Model (IBM)
      can predict nurses' intentions to administer PRN opioid analgesics for pain
      relief to hospitalized postoperative orthopaedic patients. METHODS: A
      nonexperimental, cross-sectional quantitative format was used. The sample
      consisted of 800 nurses. Data collection was done by survey. RESULTS: Path
      analysis revealed the significant predictors of nurses' intention to administer
      opioid analgesics to be self-efficacy (beta= 0.15), normative beliefs (beta=
      0.21), and salience (importance) of the behavior (beta= 0.25). CONCLUSION: The
      study showed that the IBM constructs are useful for predicting intentions toward
      performance of a professional behavior. The inclusion of self-efficacy,
      underlying beliefs, and salience of the behavior was new and unique contributions
      to the existing body of knowledge.

PMID- 29189624
TI  - Preoperative Risk Factors for Subsyndromal Delirium in Older Adults Who Undergo
      Joint Replacement Surgery.

PMID- 29189625
TI  - Adolescents' Experiences of Scoliosis Surgery and the Trajectory of Self-Reported
      Pain: A Mixed-Methods Study.
AB  - Scoliosis surgery for adolescents is a major surgery with a difficult recovery.
      In this study, a mixed-methods design was used to broaden the scope of
      adolescents' experiences of surgery for idiopathic scoliosis and the trajectory
      of self-reported pain during the hospital stay and through the first 6 months of
      recovery at home. Self-reports of pain, diaries, and interviews were analyzed
      separately. The results were then integrated with each other. The trajectory of
      self-reported pain varied hugely between individuals. Adolescents experienced
      physical suffering and struggled to not be overwhelmed. The adolescents described
      the environmental and supportive factors that enabled them to cope and how they
      hovered between suffering and control as they strived toward normality. This
      study highlights areas of potential improvement in perioperative scoliosis care
      in terms of nursing support and pain management.

PMID- 29189623
TI  - Preoperative Risk Factors for Subsyndromal Delirium in Older Adults Who Undergo
      Joint Replacement Surgery.
AB  - BACKGROUND: Older adults with subsyndromal delirium have similar risks for
      adverse outcomes following joint replacement surgery as those who suffer from
      delirium. PURPOSE: This study examined relationships among subsyndromal delirium
      and select preoperative risk factors in older adults following major orthopaedic
      surgery. METHODS: Delirium assessments of a sample of 62 adults 65 years of age
      or older were completed on postoperative Days 1, 2, and 3 following joint
      replacement surgery. Data were analyzed for relationships among delirium symptoms
      and the following preoperative risk factors: increased comorbidity burden,
      cognitive impairment, fall history, and preoperative fasting time. RESULTS:
      Postoperative subsyndromal delirium occurred in 68% of study participants. A
      recent fall history and a longer preoperative fasting time were associated with
      delirium symptoms (p <= .05). CONCLUSIONS: Older adults with a recent history of
      falls within the past 6 months or a longer duration of preoperative fasting time
      may be at higher risk for delirium symptoms following joint replacement surgery.

PMID- 29189626
TI  - Organizational Learning in an Orthopaedic Unit: A Learning History.
AB  - The purpose of this study was to explore organizational learning in an
      orthopaedic hospital unit. Skill in organizational learning is necessary to
      achieve high reliability in a dynamic healthcare environment, yet organizational
      learning in hospital units is not well understood. A learning history was
      conducted with a high-performing orthopaedic unit. Findings were interpreted in
      the context of a previous learning history conducted with a critical care unit.
      Despite contextual differences, each unit progressed through the same four
      developmental stages to achieve its current state of high reliability. On both
      units, psychological safety and a healthy work environment proved essential for
      developmental progression. Hospital units may progress through distinct
      developmental stages to achieve their desired outcomes. Psychological safety and
      a healthy work environment appear foundational to organizational learning in
      hospital units. Nursing leaders should work with team members to evaluate their
      unit's development and use suggested strategies to facilitate organizational
      learning.

PMID- 29189628
TI  - Screening for Posttraumatic Stress Disorder in Civilians With Mangled Hand
      Injury: A Practice Enhancement Approach.
AB  - Posttraumatic stress disorder (PTSD) is a symptom cluster of intrusion,
      avoidance, negative alteration in cognition, and alteration in arousal and
      reactivity following trauma. PTSD occurs frequently after a physical trauma such
      as a severe hand injury. It is often not recognized and consequently untreated.
      Previous research has shown that 10%-40% of civilian trauma survivors experience
      PTSD in the first 12 months after injury. There is great urgency to identify
      patients in the early stage of recovery from trauma, as PTSD becomes more
      difficult to treat in its chronic form. Mangling hand injuries are particularly
      disabling because they are an integral part of our social body image. We wanted
      to investigate the degree of PTSD screening and the follow-up-referral procedures
      in all mangled hand cases at the hand clinic of a large Northwestern Trauma
      Center. A retrospective medical record review was conducted from January to
      December 2012 using an existing PTSD screen with data from the electronic medical
      records. We found that 40% of the patients with mangled hand injury were
      classified as "at risk" according to our PTSD screening but only 22% of those
      cases were referred to rehabilitation psychiatry for further evaluation and
      treatment. The low rate of referral for PTSD after mangled hand injury was
      alarming. On the basis of this, we instituted a new screening protocol for all
      patients with mangled hand injury using the 4-item Primary Care-PTSD screening
      tool and provided an informational brochure on PTSD. The investigation led to a
      positive change in the practice environment and workflow of the clinic. We have
      not conducted any follow-up study as yet, but our goal is to screen all patients
      with mangled hand injury and refer all patients for psychiatric therapy who have
      positively answered 3 of the 4 screening questions.

PMID- 29189630
TI  - Calcific Tendinitis of the Shoulder.

PMID- 29189629
TI  - Calcific Tendinitis of the Shoulder.

PMID- 29189631
TI  - Incidence and Risk Factors of Intracranial Hemorrhage in Liver Transplant
      Recipients.
AB  - BACKGROUND: Intracranial hemorrhage after liver transplantation is an
      infrequently reported complication but one which can have devastating
      consequences. METHODS: We performed a retrospective cross-sectional analysis of
      all liver transplants performed between January 2010 and June 2015 at a single
      high-volume institution using a prospectively maintained electronic database and
      query of the electronic medical record. Cases of intracranial hemorrhage were
      adjudicated as either spontaneous intraparenchymal hemorrhage(IPH) or extra-axial
      hemorrhage (EAH). Patients with confirmed intracranial hemorrhage were compared
      with all other liver transplant recipients. Risk factors were identified by
      univariate analysis and logistic regression models for IPH and EAH. RESULTS:
      Thirty-one (5.2%) of 595 liver transplant recipients developed an intracranial
      hemorrhage within 12 months of transplantation, 15 IPH and 16 EAH. The majority
      of intracranial hemorrhages were diagnosed within 1 month of transplantation.
      Eight (26%) intracranial hemorrhage patients died during hospitalization.
      Fourteen (45%) intracranial hemorrhage patients died within 1 year of
      transplantation and 1-year mortality was greater than in patients without
      intracranial hemorrhage (11.2%, P < 0.01). Female sex (adjusted odds ratio [OR],
      3.291; 95% confidence interval [CI], 1.092-9.924; P = 0.034), higher
      pretransplant bilirubin (adjusted OR, 1.037; 95% CI, 1.006-1.070; P = 0.020), and
      greater increase in pretransplant to posttransplant systolic blood pressure
      (adjusted OR, 1.029; 95% CI, 1.006-1.052; P = 0.012) were associated with
      posttransplant IPH. Lower pretransplant serum fibrinogen level (adjusted OR,
      0.988; 95% CI, 0.979-0.998; P = 0.017) was associated with posttransplant EAH.
      CONCLUSIONS: Postoperative blood pressure control and pretransplant fibrinogen
      levels may be modifiable risk factors for preventing posttransplant intracranial
      hemorrhage.

PMID- 29189632
TI  - End-of-Treatment Positron Emission Tomography After Uniform First-Line Therapy of
      B-Cell Posttransplant Lymphoproliferative Disorder Identifies Patients at Low
      Risk of Relapse in the Prospective German PTLD Registry.
AB  - BACKGROUND: Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography
      (PET) is a recommended standard in the staging and response assessment of 18F-FDG
      avid lymphoma. Posttransplant lymphoproliferative disorder (PTLD) can be detected
      by 18F-FDG-PET at diagnosis with high sensitivity and specificity. However, the
      role of response assessment by end-of-treatment (EOT) PET has only been addressed
      in small case series. METHODS: We performed a retrospective, multicenter study of
      37 patients with CD20-positive PTLD after solid organ transplantation treated
      with uniform, up-to-date, first-line protocols in the prospective German PTLD
      registry who had received EOT 18F-FDG-PET between 2006 and 2014. Median follow-up
      was 5.0 years. Any nonphysiological 18F-FDG uptake (Deauville score greater 2)
      was interpreted as PET-positive. RESULTS: By computed tomography (CT) final
      staging, 18 of 37 patients had a complete response, 18 had a partial response and
      1 patient had stable disease. EOT PET was negative in 24 of 37 patients and
      positive in 13 of 37 patients. The positive predictive value of EOT PET for PTLD
      relapse was 38%, and the negative predictive value was 92%. Time to progression
      (TTP) and progression-free-survival were significantly longer in the PET negative
      group (P = 0.019 and P = 0.013). In the 18 patients in a partial response by CT
      staging, we noted highly significant differences in overall survival (P = 0.001),
      time to progression (P = 0.007), and progression-free survival (P < 0.001) by EOT
      PET. CONCLUSIONS: Even without baseline imaging, EOT PET in PTLD identifies
      patients at low risk of relapse and offers clinically relevant information,
      particularly in patients in a partial remission by CT staging.

PMID- 29189633
TI  - Lung Transplantation as a Therapeutic Option in Acute Respiratory Distress
      Syndrome.
AB  - BACKGROUND: Lung transplantation (LTPL) is considered as a salvage therapeutic
      option in patients with end-stage lung disease. However, there is a lack of
      sufficient data on the use of LTPL in patients with acute respiratory distress
      syndrome (ARDS). Although there are few case reports on lung transplant for ARDS,
      no case series exists up to date. The aim of this study was to evaluate the
      clinical outcomes of patients with ARDS in accordance with the LTPL status.
      METHODS: Patients who had severe ARDS (PaO2/FiO2 ratio <= 100 mm Hg with positive
      end-expiratory pressure >= 5 cm H2O) and were listed for LTPL with no underlying
      end-stage lung disease were included in this single-center retrospective study.
      Demographic and clinical data of the patients were collected and analyzed.
      RESULTS: Fourteen patients were listed for LTPL due to severe ARDS. All patients
      received mechanical ventilation, and 12 (86%) patients underwent extracorporeal
      membrane oxygenation. Of the 9 patients who underwent LTPL, 8 (89%) survived,
      whereas only 1 (20%) patient out of those who did not receive LTPL survived. The
      median survival time of the patients who underwent LTPL was 1996 days
      (interquartile range [IQR], 872-2239), compared with 49 days (IQR, 872-2239) in
      patients who did not undergo LTPL. The median survival time after LTPL was 64
      months (IQR, 28-72). The 3-year survival rate of the recipients was 78%.
      CONCLUSIONS: LTPL may be considered as a therapeutic option in a select group of
      patients with severe ARDS. However, the irreversibility of the patient's lung
      status should be considered.

PMID- 29189634
TI  - Alpha band frequency differences between low-trait and high-trait anxious
      individuals.
AB  - Trait anxiety has been shown to cause significant impairments on attentional
      tasks. Current research has identified alpha band frequency differences between
      low-trait and high-trait anxious individuals. Here, we further investigated the
      underlying alpha band frequency differences between low-trait and high-trait
      anxious individuals during their resting state and the completion of an
      inhibition executive functioning task. Using human participants and quantitative
      electroencephalographic recordings, we measured alpha band frequency in
      individuals both high and low in trait anxiety during their resting state, and
      while they completed an Eriksen Flanker Task. Results indicated that high-trait
      anxious individuals exhibit a desynchronization in alpha band frequency from a
      resting state to when they complete the Eriksen Flanker Task. This suggests that
      high-trait anxious individuals maintain fewer attentional resources at rest and
      must martial resources for task performance as compared with low-trait anxious
      individuals, who appear to maintain stable cognitive resources between rest and
      task performance. These findings add to the cognitive neuroscience literature
      surrounding the role of alpha band frequency in low-trait and high-trait anxious
      individuals.

PMID- 29189635
TI  - When the body becomes no more than the sum of its parts: the neural correlates of
      scrambled versus intact sexualized bodies.
AB  - Recent research found that configural information is less important for the
      processing of sexualized bodies than for the processing of nonsexualized bodies.
      The present investigation aims to expand these findings by directly manipulating
      configural versus analytic processing of sexualized and nonsexualized bodies. We
      posited that disrupting first-order relational information through scrambling
      should be associated with larger N170 amplitudes (scrambling effect) for
      nonsexualized bodies, whereas the scrambling manipulation should not modulate
      N170 amplitudes associated with sexualized bodies and objects. We presented
      images of scrambled versus intact sexualized bodies, nonsexualized bodies, and
      objects while the N170 was recorded. Consistent with our hypothesis, we found
      that the scrambling manipulation was associated with larger N170 amplitudes for
      nonsexualized bodies (i.e. scrambling effect), whereas no scrambling effect
      emerged for sexualized bodies and objects. This research is the first to show
      that sexualized bodies are processed analytically at a neural level. Implications
      for the literature in body perception and objectification will be discussed.

PMID- 29189636
TI  - Mitochondrial fusion and fission proteins and the recognition memory of
      imprinting in domestic chicks.
AB  - Visual imprinting is a learning process through which young, visually naive
      animals come to recognize a visual stimulus by being exposed to it (training) and
      subsequently approach the stimulus in preference to others. A large body of
      evidence indicates that a restricted part of the forebrain, the intermediate
      medial mesopallium (IMM), is a memory region for visual imprinting in the
      domestic chick. Previous studies have shown learning-related up-regulation of
      several mitochondrial proteins in the IMM 24 h after training. Learning-related
      increases in transcription factors involved in mitochondrial biogenesis were
      found without significant change in mitochondrial DNA copy number, but the issue
      of whether mitochondrial fusion or fission processes change with learning was
      unresolved. The present study enquired whether proteins involved in mitochondrial
      fusion and fission contribute to memory following imprinting. Tissue was sampled
      from the left and right IMM, and the left and right posterior pole of the
      nidopallium (a control brain region not involved in imprinting). The amounts of
      the following proteins were measured by Western immunoblotting 24 h after
      training: mitochondrial mitofusin-1 (MTF-1, as indicator of mitochondrial
      fusion), membrane dynamin-related protein-1 (DRP-1, as indicator of mitochondrial
      fission) and cytoplasmic DRP-1. Learning-related increases in MTF-1 and DRP-1
      were observed bilaterally in the IMM, but not in either side of the posterior
      pole of the nidopallium. Cytoplasmic DRP-1 was not changed significantly in any
      region studied. The results implicate increased, balanced levels of mitochondrial
      fusion and fission in memory formation up to 24 h after training.Supplementary
      Video Abstract (Supplemental digital content 1, http://links.lww.com/WNR/A446).

PMID- 29189637
TI  - Strategies for Prevention and Management of Bleeding Following Pediatric Cardiac
      Surgery on Cardiopulmonary Bypass: A Scoping Review.
AB  - OBJECTIVE: We aimed to systematically describe, via a scoping review, the
      literature reporting strategies for prevention and management of mediastinal
      bleeding post pediatric cardiopulmonary bypass surgery. DATA SOURCES: MEDLINE,
      EMBASE, PubMed, and Cochrane CENTRAL Register. STUDY SELECTION: Two authors
      independently screened publications from 1980 to 2016 reporting the effect of
      therapeutic interventions on bleeding-related postoperative outcomes, including
      mediastinal drain loss, transfusion, chest re-exploration rate, and coagulation
      variables. Inclusions: less than 18 years, cardiac surgery on cardiopulmonary
      bypass. DATA EXTRACTION: Data from eligible studies were extracted using a
      standard data collection sheet. DATA SYNTHESIS: Overall, 299 of 7,434 screened
      articles were included, with observational studies being almost twice as common
      (n = 187, 63%) than controlled trials (n = 112, 38%). The most frequently
      evaluated interventions were antifibrinolytic drugs (75 studies, 25%), blood
      products (59 studies, 20%), point-of-care testing (47 studies, 16%), and
      cardiopulmonary bypass circuit modifications (46 studies, 15%). The publication
      rate for controlled trials remained constant over time (4-6/yr); however, trials
      were small (median participants, 51; interquartile range, 57) and overwhelmingly
      single center (98%). Controlled trials originated from 22 countries, with the
      United States, India, and Germany accounting for 50%. The commonest outcomes were
      mediastinal blood loss and transfusion requirements; however, these were defined
      inconsistently (blood loss being reported over nine different time periods). The
      majority of trials were aimed at bleeding prevention (98%) rather than treatment
      (10%), nine studies assessed both. CONCLUSIONS: Overall, this review demonstrates
      small trial sizes, low level of evidence, and marked heterogeneity of reported
      endpoints in the included studies. The need for more, higher quality studies
      reporting clinically relevant, comparable outcomes is highlighted. Emerging
      fields such as the use of coagulation factor concentrates, goal-directed
      guidelines, and anti-inflammatory therapies appear to be of particular interest.
      This scoping review can potentially guide future trial design and form the basis
      for therapy-specific systematic reviews.

PMID- 29189639
TI  - Effects of Closed Endotracheal Suctioning on Systemic and Cerebral Oxygenation
      and Hemodynamics in Children.
AB  - OBJECTIVES: To evaluate the effects of closed endotracheal tube suctioning on
      systemic oxygen saturation, cerebral regional oxygen saturation, and somatic
      regional (renal) oxygen saturation and hemodynamic variables in children. DESIGN:
      Prospective observational. SETTING: A tertiary care PICU. SUBJECTS: Children aged
      0-18 years, requiring invasive mechanical ventilation and with an arterial line.
      INTERVENTIONS: Closed endotracheal suction. MEASUREMENTS AND MAIN RESULTS: The
      study included 19 sedated and intubated children, 0-18 years old. They were
      enrolled in an ongoing prospective observational study. We used near-infrared
      spectroscopy for cerebral regional oxygen saturation and somatic regional (renal)
      oxygen saturation. The timing of each closed endotracheal tube suctioning event
      was accurately identified from video recordings. We extracted systemic oxygen
      saturation, cerebral regional oxygen saturation, somatic regional (renal) oxygen
      saturation, heart rate, and systolic blood pressure and diastolic blood pressure
      for 5 minutes before and 5 minutes after each event and used these data for
      analysis. One-minute average values of these variables were used for repeated
      measures analysis. We analyzed 287 endotracheal tube suctioning episodes in 19
      children. Saline was instilled into the endotracheal tube during 61 episodes. The
      mean heart rate (107.0 +/- 18.7 vs 110.2 +/- 10.4; p < 0.05), mean arterial blood
      pressure (81.5 +/- 16.1 vs 83.0 +/- 15.6 mm Hg; p < 0.05), and the mean cerebral
      regional oxygen saturation (64.8 +/- 8.3 vs 65.8 +/- 8.3; p < 0.05) were
      increased after suctioning. The mean systemic oxygen saturation (96.9 +/- 2.7 vs
      96.7 +/- 2.7; p = 0.013) was decreased, whereas the mean somatic regional (renal)
      oxygen saturation was not significantly different after endotracheal tube
      suctioning. Repeated-measures analysis revealed transient increases in heart
      rate, respiratory rate, systolic blood pressure, and diastolic blood pressure; a
      sustained increase in cerebral regional oxygen saturation; and transient
      decreases in systemic oxygen saturation and somatic regional (renal) oxygen
      saturation. Saline instillation did not affect oxygenation or hemodynamic
      variables. CONCLUSIONS: Closed endotracheal tube suctioning in sedated children
      is associated with transient but clinically insignificant changes in heart rate,
      blood pressure, cerebral regional oxygen saturation, systemic oxygen saturation,
      and somatic regional (renal) oxygen saturation. Saline instillation during
      endotracheal tube suctioning had no adverse effects on systemic or cerebral
      oxygenation.

PMID- 29189638
TI  - Viral DNAemia and Immune Suppression in Pediatric Sepsis.
AB  - OBJECTIVES: Demonstrate that DNA viremia is common in pediatric sepsis and
      quantitate its associations with host immune function and secondary infection
      risk. DESIGN: Retrospective analysis of a prospective cohort study. PATIENTS:
      Seventy-three children admitted with sepsis-induced organ failure. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: This study was performed as an ancillary
      investigation to a single-center prospective study of children with severe
      sepsis. Longitudinally collected, batched, frozen plasma was examined using real
      time-polymerase chain reaction for the presence of cytomegalovirus, Epstein-Barr
      virus, herpes simplex virus, human herpes virus-6, torque teno virus, and
      adenovirus DNA. Innate immune function was also measured longitudinally via
      quantification of ex vivo lipopolysaccharide -induced tumor necrosis factor-alpha
      production capacity. Viral DNAemia with a virus other than torque teno virus was
      detected in 28 of 73 subjects (38%) and included cytomegalovirus 5%, Epstein-Barr
      virus 11%, herpes simplex virus 4%, human herpes virus-6 8%, and adenovirus 26%.
      In addition, torque teno virus was detected in 89%. Epstein-Barr virus DNAemia
      was associated with preexisting immune suppression (p = 0.007) Viral DNAemia was
      associated with preexisting immune suppression and high risk for the subsequent
      development of secondary infection (p < 0.05 for both). Subjects with viral
      DNAemia had lower innate immune function over time compared with those who were
      virus negative (p < 0.05). CONCLUSIONS: DNAemia from multiple viruses can be
      detected in septic children and is strongly associated with preexisting immune
      suppression and secondary infection risk. The role of DNA viruses in the
      perpetuation of impaired host defense in this setting should be the subject of
      prospective study.

PMID- 29189641
TI  - MRI Characteristics of Spinal Ependymoma in WHO Grade II: A Review of 59 Cases.
AB  - STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: The goal of this study
      is to determine the characteristic imaging features of spinal ependymoma in a
      review of magnetic resonance imaging (MRI) data for a large series of surgically
      proven cases. SUMMARY OF BACKGROUND DATA: Common spinal intramedullary neoplasms
      are mostly ependymomas and comprise 50% to 60% of spinal neuroepithelial tumors
      in adults. Preoperative prediction of the pathological diagnosis could enhance
      surgical planning and explanation of the procedure to patients. However, these
      types of tumors exhibit a variety of MRI findings. METHODS: Records were examined
      for 59 patients who underwent surgery for spinal cord ependymoma and had a
      pathological diagnosis of cellular ependymoma of World Health Organization
      classification grade II. RESULTS: The ependymomas included 28 in the cervical
      spine, 34 in the thoracic spine, and 3 conus lesions. All cases were isointense
      or hypointense on T1-weighted MRI, and 55 (93%) were hyperintense on T2-weighted
      MRI. Tumors were located centrally in all cases; 50 (85%) showed surrounding cord
      edema; and 52 (88%) had associated cysts, including 36 (61%) rostral or caudal
      cysts, 10 (17%) intratumoral cysts, and 6 (10%) with syringomyelia. Of the 59
      tumors, 17 (29%) showed the "cap sign," a rim of extreme hypointensity seen
      around the tumor on T2-weighted images, due to hemosiderin. In gadolinium
      enhanced MRI, all cases were enhanced, and 27 (46%), 16 (27%), 11 (19%), and 5
      (8%) cases showed homogeneous, heterogeneous, rim, and nodular enhancement,
      respectively. CONCLUSION: Hypointense changes on T2-weighted MRI and hemosiderin
      deposition reflect easy bleeding. Tumors are associated with various types of
      cysts, and gadolinium-enhancement patterns reflect a variety of intratumor
      cellular components. In cases in which the whole tumor shows gadolinium
      enhancement on MRI, rostral, or caudal cyst and a cap sign with hemorrhage are
      characteristics of grade II classical ependymoma. LEVEL OF EVIDENCE: 3.

PMID- 29189642
TI  - VANGL1 Is Not Associated With the Susceptibility of Adolescent Idiopathic
      Scoliosis in the Chinese Population.
AB  - STUDY DESIGN: A case-control study. OBJECTIVE: To replicate the association
      between the VANGL1 gene and the susceptibility of AIS in the Chinese population.
      SUMMARY OF BACKGROUND DATA: The mutations of VANGL1 gene were recently reported
      to be associated with AIS in the Danish population. However, there is a lack of
      replication in other populations. Further analysis of the functional role of
      VANGL1 in AIS was warranted. METHODS: A total of 1481 female AIS patients and
      1372 age-matched healthy controls were included in this study. single nucleotide
      variant (SNV)s c.407T > A and c.1318T > G were genotyped using allelic-specific
      multiple ligase detection reactions. single nucleotide polymorphism (SNP)s
      covering VANGL1 gene were selected using Haploview (v2.6). The associations
      between theses SNPs and AIS were investigated through Cochran-Armitage trend test
      by PLINK (v1.90). Relative mRNA expression of VANGL1 in the paraspinal muscles
      was analyzed for 30 patients and 24 age-matched controls. The difference of mRNA
      expression level between the two groups was analyzed with the Student t test.
      RESULTS: There was no case of mutation for all the subjects. A total of 22 SNPs
      covering VANGL1 were analyzed. All the SNPs were found to have comparable
      distribution of genotype and allele frequency in the cases and the controls.
      Moreover, there was no significant difference regarding the mRNA expression of
      VANGL1 in the two groups. CONCLUSION: VANGL1 gene is not associated with AIS in
      the Chinese population. Replication studies in other ethnic groups are warranted
      to further clarify the role of the VANGL1 gene in AIS. LEVEL OF EVIDENCE: 4.

PMID- 29189640
TI  - Associations of Race and Ethnicity With Patient-Reported Outcomes and Health Care
      Utilization Among Older Adults Initiating a New Episode of Care for Back Pain.
AB  - STUDY DESIGN: Secondary analysis of the Back Pain Outcomes using Longitudinal
      Data (BOLD) cohort study. OBJECTIVE: To characterize associations of self
      reported race/ethnicity with back pain (BP) patient-reported outcomes (PROs) and
      health care utilization among older adults with a new episode of care for BP.
      SUMMARY OF BACKGROUND DATA: No prior longitudinal studies have characterized
      associations between multiple race/ethnicity groups, and BP-related PROs and
      health care utilization in the United States. METHODS: This study included 5117
      participants >=65 years from three US health care systems. The primary BP-related
      PROs were BP intensity and back-related functional limitations over 24 months.
      Health care utilization measures included common diagnostic tests and treatments
      related to BP (spine imaging, spine-related relative value units [RVUs], and
      total RVUs) over 24 months. Analyses were adjusted for multiple potential
      confounders including sociodemographics, clinical characteristics, and study
      site. RESULTS: Baseline BP ratings were significantly higher for blacks vs.
      whites (5.8 vs. 5.0; P < 0.001). Participants in all race/ethnicity groups showed
      statistically significant, but modest improvements in BP over 24 months. Blacks
      and Hispanics did not have statistically significant improvement in BP-related
      functional limitations over time, unlike whites, Asians, and non-Hispanics;
      however, the magnitude of differences in improvement between groups was small.
      Blacks had less spine-related health care utilization over 24 months than whites
      (spine-related RVU ratio of means 0.66, 95% confidence interval [CI] 0.51-0.86).
      Hispanics had less spine-related health care utilization than non-Hispanics
      (spine-related RVU ratio of means 0.60; 95% CI 0.40-0.90). CONCLUSION: Blacks and
      Hispanics had slightly less improvement in BP-related functional limitations over
      time, and less spine-related health care utilization, as compared to whites and
      non-Hispanics, respectively. Residual confounding may explain some of the
      association between race/ethnicity and health outcomes. Further studies are
      needed to understand the factors underlying these differences and which
      differences reflect disparities. LEVEL OF EVIDENCE: 3.

PMID- 29189643
TI  - Inter- and Intra-rater Reliability of the Hart-ISSG Proximal Junctional Failure
      Severity Scale.
AB  - STUDY DESIGN: Reliability/external validation study. OBJECTIVE: Investigate inter
      and intrarater reliability of the Hart-International Spine Study Group (ISSG)
      Proximal Junctional Failure Severity Scale (PJFSS) and its correlation with
      operative revision in patients with proximal junctional failure (PJF). SUMMARY OF
      BACKGROUND DATA: The Hart-ISSG PJFSS is a validated classification system for
      PJF. Reliability of the PJFSS has not been assessed. METHODS: Sixteen detailed
      clinical scenarios were assessed using the ISSG PJFSS classification in six
      categories: neurologic status, axial pain, instrumentation issue, proximal
      kyphotic angle, level of upper instrumented vertebrae (UIV), and severity of
      UIV/UIV+1 fracture. Eleven spine surgeons evaluated each case in all six
      categories during two different assessments, and provided recommendations
      regarding operative revision or observation for each case. Inter- and intrarater
      reliability were calculated based on intraclass correlation coefficients.
      RESULTS: All intraclass correlation coefficients demonstrated "almost perfect"'
      (0.817-0.988) inter-rater agreement for both assessments, except UIV/UIV+1
      fracture severity during the second assessment, which demonstrated "substantial"
      agreement' (0.692). Five of six categories had "almost perfect" mean intrarater
      reliability (0.805-0.981), while "instrumentation issue" demonstrated
      "substantial" mean agreement (0.757). Inter-rater reliability for recommendation
      of surgical intervention was "almost perfect" during both assessments (0.911 and
      0.922, respectively). Mean PJFSS scores between the two assessments were
      significantly higher for cases recommended for operative revision (8.43 +/- 0.90)
      versus cases recommended for observation (P < 0.0001). CONCLUSION: The ISSG PJFSS
      is a reliable and repeatable classification system for assessing patients with
      PJF. Higher PJFSS scales correlate with recommendation for operative revision,
      extending prior external validation of the PJFSS. LEVEL OF EVIDENCE: 3.

PMID- 29189644
TI  - Identifying Factors Predictive of Atlantoaxial Fusion Failure in Pediatric
      Patients: Lessons Learned From a Retrospective Pediatric Craniocervical Society
      Study.
AB  - STUDY DESIGN: Multicenter retrospective cohort study with multivariate analysis.
      OBJECTIVE: To determine factors predictive of posterior atlantoaxial fusion
      failure in pediatric patients. SUMMARY OF BACKGROUND DATA: Fusion rates for
      pediatric posterior atlantoaxial arthrodesis have been reported to be high in
      single-center studies; however, factors predictive of surgical non-union have not
      been identified by a multicenter study. METHODS: Clinical and surgical details
      for all patients who underwent posterior atlantoaxial fusion at seven pediatric
      spine centers from 1995 to 2014 were retrospectively recorded. The primary
      outcome was surgical failure, defined as either instrumentation failure or fusion
      failure seen on either plain x-ray or computed tomography scan. Multiple logistic
      regression analysis was undertaken to identify clinical and technical factors
      predictive of surgical failure. RESULTS: One hundred thirty-one patients met the
      inclusion criteria and were included in the analysis. Successful fusion was seen
      in 117 (89%) of the patients. Of the 14 (11%) patients with failed fusion, the
      cause was instrumentation failure in 3 patients (2%) and graft failure in 11
      (8%). Multivariate analysis identified Down syndrome as the single factor
      predictive of fusion failure (odds ratio 14.6, 95% confidence interval [3.7
      64.0]). CONCLUSION: This retrospective analysis of a multicenter cohort
      demonstrates that although posterior pediatric atlantoaxial fusion success rates
      are generally high, Down syndrome is a risk factor that significantly predicts
      the possibility of surgical failure. LEVEL OF EVIDENCE: 3.

PMID- 29189645
TI  - A Multicenter Radiographic Evaluation of the Rates of Preoperative and
      Postoperative Malalignment in Degenerative Spinal Fusions.
AB  - STUDY DESIGN: Multicenter, retrospective, institutional-review-board -approved
      study at 18 institutions in the United States with 24 treating investigators.
      OBJECTIVE: This study was designed to retrospectively assess the prevalence of
      spinopelvic malalignment in patients who underwent one- or two-level lumbar
      fusions for degenerative (nondeformity) indications and to assess the incidence
      of malalignment after fusion surgery as well as the rate of alignment
      preservation and/or correction in this population. SUMMARY OF BACKGROUND DATA:
      Spinopelvic malalignment after lumbar fusion has been associated with lower
      postoperative health-related quality of life and elevated risk of adjacent
      segment failure. The prevalence of spinopelvic malalignment in short-segment
      degenerative lumbar fusion procedures from a large sample of patients is
      heretofore unreported and may lead to an under-appreciation of these factors in
      surgical planning and ultimate preservation or correction of alignment. METHODS:
      Lateral preoperative and postoperative lumbar radiographs were retrospectively
      acquired from 578 one- or two-level lumbar fusion patients and newly measured for
      lumbar lordosis (LL), pelvic incidence (PI), and pelvic tilt. Patients were
      categorized at preop and postop time points as aligned if PI-LL < 10 degrees  or
      malaligned if PI-LL>=10 degrees . Patients were grouped into categories based on
      their alignment progression from pre- to postoperative, with preserved (aligned
      to aligned), restored (malaligned to aligned), not corrected (malaligned to
      malaligned), and worsened (aligned to malaligned) designations. RESULTS:
      Preoperatively, 173 (30%) patients exhibited malalignment. Postoperatively, 161
      (28%) of patients were malaligned. Alignment was preserved in 63%, restored in
      9%, not corrected in 21%, and worsened in 7% of patients. CONCLUSION: This is the
      first multicenter study to evaluate the preoperative prevalence and postoperative
      incidence of spinopelvic malalignment in a large series of short-segment
      degenerative lumbar fusions, finding over 25% of patients out of alignment at
      both time points, suggesting that alignment preservation/restoration
      considerations should be incorporated into the decision-making of even
      degenerative lumbar spinal fusions. LEVEL OF EVIDENCE: 3.

PMID- 29189647
TI  - The Use of Simulation in Physician Assistant Programs: A National Survey.
AB  - PURPOSE: The purpose of this study was to develop a national-level description of
      the current use of simulation activities in physician assistant (PA) education
      and to assess the degree to which the use of simulation varies by PA program size
      and institutional type. METHODS: An electronic survey on medical simulation was
      sent to 177 PA program directors or to a designated simulation activities
      coordinator, using the directory on the Physician Assistant Education Association
      website. The survey addressed program characteristics, types of simulation
      modalities in use, and frequency of use of those modalities in PA training. The
      specific content areas addressed were error disclosure, medical knowledge,
      patient care, and psychomotor skills. RESULTS: The survey was emailed 3 times
      from early April to mid-May 2014, with a follow-up call to nonrespondents in
      August 2014. Of the 177 PA programs contacted, 63 completed the survey, for a
      response rate of 35.6%. Results indicate widespread use of simulation by survey
      respondents, especially in teaching, assessment of medical knowledge, and
      clinical skills, with somewhat lower levels of use in content areas such as error
      disclosure, delivery of bad news, and team training. CONCLUSIONS: Although
      barriers exist to its use in training health care professionals, simulation has
      become an important tool for training PAs in a variety of medical and
      interpersonal skills. It is also clear that simulation is an important tool for
      conducting interprofessional training. More research is needed to identify
      optimal approaches to the use of simulation in health care professions training.

PMID- 29189646
TI  - The Impact of Early Involvement in a Postdischarge Support Program for Ostomy
      Surgery Patients on Preventable Healthcare Utilization.
AB  - PURPOSE: To evaluate the impact of a postdischarge ostomy support program as an
      adjunct to nurse-led ostomy care on preventable healthcare utilization. DESIGN: A
      cross-sectional study. SUBJECTS AND SETTING: A postdischarge support program
      offered by an ostomy product's manufacturer provides persons living with an
      ostomy with patient-centered and easily accessible assistance. Individuals who
      underwent ostomy surgery within 18 months prior to the survey date were selected
      from an ostomy patient database maintained by the ostomy patient support program
      provider. Of 7026 surveys sent to program enrollees, 493 (7%) responded, compared
      with 225 (5%) out of 4149 surveys sent to individuals in a comparison group. The
      2 groups were similar in demographics. A majority of the survey respondents were
      female (60% of program enrollees vs 55% of respondents in the comparison group).
      Among the program enrollees, 44% had colostomy, 43% had ileostomy, 10% had
      urostomy, and 4% had at least 2 types of ostomy surgery compared with 52%, 32%,
      12%, and 4% of the respondents in a comparison group, respectively. METHODS: The
      study compared hospital readmission and emergency room (ER) visit rates
      attributable to ostomy complications between program enrollees and respondents in
      the comparison group. The event rates were measured in 2 study periods: within
      the first month of discharge and after the first month of discharge. Eligible
      individuals received an online survey that included the following domains:
      characteristics of ostomy surgery; readmissions and ER visits within the first
      month or after the first month of discharge, including reasons for preventable
      events; and level of health care access. Multivariate logistic regressions
      controlling for covariates were applied to investigate associations between
      program enrollment and ostomy-related readmission or ER visit rates. RESULTS:
      Logistic regression analyses showed that, when compared with respondents in the
      comparison group, program enrollees had a significantly lower likelihood of being
      readmitted and visiting the ER due to ostomy complications after the first month
      of hospital discharge and up to 18 months postdischarge (odds ratio [OR] = 0.45;
      95% confidence interval [CI], 0.27-0.73; and OR = 0.37; 95% CI, 0.22-0.64,
      respectively). CONCLUSIONS: Findings suggest that enrolling patients in the
      postdischarge ostomy support program provides an effective approach to reducing
      preventable healthcare utilization.

PMID- 29189648
TI  - Quantifying Cadaver Use in Physician Assistant Anatomy Education.
AB  - PURPOSE: To quantify the number of cadavers used in physician assistant (PA)
      anatomy education and to ascertain the origins of those cadavers. METHODS: An
      electronic survey was generated and distributed to all schools that had been
      accredited by the Accreditation Review Commission on Education for the Physician
      Assistant. Responses were reported using descriptive statistics. RESULTS: The
      survey had a 49% response rate. Among the responding programs, 79% reported
      working with 655 cadavers, with an average of one cadaver per 5.72 students.
      Programs reported that 21% receive cadavers from multiple sources. Of all
      programs using cadavers, 62% receive cadavers from medical schools, 23% from in
      house anatomical gift programs, 19% from state anatomy boards, 9% from private
      organizations, and 8% from other sources. Anatomy educators reported that 55%
      know the origins of the cadavers in their programs, 18% do not, and 27% are
      uncertain. In categorizing cadavers at their programs, 56% were reported as
      registered donors, 4% as next-of-kin donations, 1% as unclaimed dead, 17% as
      uncertain origin, and 22% as unaccounted for by respondents. CONCLUSIONS: Among
      educators who teach anatomy to PA students, 45% do not know or are uncertain of
      the origins of the cadavers in their programs. Of the reported 655 cadavers used
      in PA education, 289 were not categorized as registered donors. Facing the
      expansion of PA programs, educators need to be aware of cadavers' origins to
      ensure that all aspects of PA education are consistent with the ethics that the
      students are being taught. Those ethics include the need for informed consent for
      all cadavers involved in PA education.

PMID- 29189649
TI  - Physician Assistant Student Training for the Inpatient Setting: A Needs
      Assessment.
AB  - PURPOSE: The number of physician assistants (PAs) practicing hospital medicine is
      rapidly expanding. Little research has been done to determine which inpatient
      medicine rotation experiences are most helpful to prepare PA students for a
      career in inpatient medicine. We aimed to determine those skills that practicing
      hospitalists believe are most critical for PA students to master and to describe
      hospitalists' current understanding of PA training. We also sought to evaluate
      the current performance of our own inpatient medicine rotation for PA students.
      METHODS: We surveyed 85 practicing hospitalists, including physicians and
      advanced-practice providers, from 3 hospitals in the Duke University Health
      System to identify (1) the clinical topics and skills deemed most essential for
      PA students on an inpatient medicine rotation, (2) the percentage of hospitalists
      able to correctly answer basic questions about PA training, and (3) current
      rotation performance. Descriptive statistics were used to summarize responses.
      RESULTS: Hospitalists identified the clinical conditions and health care systems
      with the most educational value for PA students. Hospitalists were found to have
      variable levels of understanding of the PA training pathway, with more than 20%
      incorrectly answering questions about the training process. According to mean
      responses, the rotation performed positively for 15 of 19 medical conditions. The
      majority of survey respondents suggested that a formal curriculum would help
      faculty teach and improve the learning experience for PA students. CONCLUSIONS:
      Identifying the most essential content can facilitate curriculum development.
      Hospitalists have a knowledge gap about the training of PA students. The
      inpatient medicine rotation was rated positively, but survey responses suggested
      that a formal curriculum could have a positive effect and would be well received.

PMID- 29189650
TI  - Application of Adult Learning Theory to Physician Assistant Education.
AB  - Just as we depend on medical science and research to treat patients, we should
      connect our teaching methods to educational theory and research. In particular,
      the foundations of adult education philosophy and adult learning theories can be
      deliberately applied to further strengthen the clinical learning experience of
      physician assistants (PAs). We propose that PA educators should be aware of how
      their personal philosophy of education affects their teaching practice. In
      addition, educators should apply learning theories to both classroom process and
      content. We provide an overview of 5 categories of learning philosophy (liberal,
      progressive, behavioral, humanist, and radical) and 6 learning theories
      (experiential learning, reflective practice, situated learning, communities of
      practice, transformative learning, and critical consciousness) of adult
      education. Concrete examples of how to apply adult education theory to meet
      specific learning objectives for PA students are described. Understanding how to
      apply learning theory and identify and shape one's educational philosophy
      provides theoretical and empirical support for what we often deem an intuitive
      process.

PMID- 29189651
TI  - Are You SURE You Want to Send That? A Model for Email Professionalism in Medical
      Education.
AB  - Email is an essential method of communication within academic medical
      environments and elsewhere. There is a growing body of literature that focuses on
      provider-to-patient communication in addition to studies examining the
      intersection of social networking and professionalism. Relatively little research
      exists, however, regarding the components of professional email interactions or
      "best practices" for electronic correspondence among colleagues, faculty, and
      trainees. After reviewing the existing literature, the authors created a
      practical approach for skillful email construction; the SURE model proposes a
      simplified framework that teaching institutions can use to improve
      interdisciplinary interactions and enhance email professionalism.

PMID- 29189652
TI  - Physician Assistant Student Perceptions of an Interprofessional, Peer-to-Peer
      Oral Health Curriculum Led by Dental Students.
AB  - PURPOSE: Physician assistants (PA) are health care team members who often work in
      primary care. Providing oral health education to PAs during training could
      improve oral health for vulnerable patients who seek treatment in the primary
      care setting and who are less able to access dental care. The purpose of this
      study was to assess the effectiveness of a peer-to-peer oral health curriculum
      taught by dental students to their PA student colleagues. METHODS: Dental
      students presented an interactive, case-based curriculum, followed by a hands-on
      oral examination training session. PA student feedback was obtained, and results
      were analyzed. RESULTS: Students found the content to be highly relevant and well
      presented. Conveying oral health competencies to future primary care providers
      may reduce oral health disparities. CONCLUSIONS: PA students reported improved
      understanding of oral health and indicated they would incorporate what they had
      learned into their future clinical practice.

PMID- 29189654
TI  - The Sacred Seven Elective: Integrating the Health Humanities Into Physician
      Assistant Education.

PMID- 29189653
TI  - Preceptors' Perceptions of Interprofessional Practice, Student Interactions, and
      Strategies for Interprofessional Education in Clinical Settings.
AB  - PURPOSE: This study describes clinical preceptors' perceptions of
      interprofessional practice, the nature and variety of physician assistant (PA)
      students' interprofessional interactions during clinical training, and factors
      that facilitate or hinder interprofessional education (IPE) in clinical settings.
      METHODS: This qualitative study involved interviews with preceptors that were
      audio-recorded, transcribed, and then analyzed through an iterative process to
      identify key conceptual themes. RESULTS: Fourteen preceptors from a variety of
      clinical settings participated. Four themes were identified: (1) preceptors
      define interprofessional practice differently; (2) students learn about teams by
      being a part of teams; (3) preceptors separate students to avoid diluting
      learning experiences; and (4) preceptors can facilitate IPE by introducing
      students to members of the team and role modeling team skills. CONCLUSIONS: The
      themes may inform PA educators' efforts to increase IPE in clinical settings
      through educational interventions with both preceptors and students.

PMID- 29189655
TI  - Integrating Second-Year Medical Students and First-Year Physician Assistant
      Students Into a 12-Week Ethics Course.

PMID- 29189656
TI  - From Coursework to Dissertation: Lessons Learned on the Long Road to the PhD.

PMID- 29189657
TI  - Perinatal Tuberculosis: Is It a Forgotten Disease?
AB  - Perinatal tuberculosis is an uncommon condition but with a high mortality and a
      challenging diagnosis. We present 4 cases of perinatal tuberculosis managed
      between 1991 and 2014 in a Spanish Tertiary Hospital. The infection should be
      considered in patients with progressive respiratory symptoms and with a poor
      response to conventional antibiotic therapy, especially in those with positive
      epidemiologic risk. Bronchoscopy can be a useful tool for diagnosis.

PMID- 29189659
TI  - High Prevalence of Lipid Abnormalities and Insulin Resistance Among
      Antiretroviral Naive HIV-infected Children in India.
AB  - BACKGROUND: As large numbers of children are accessing antiretroviral therapy
      (ART) in India, we evaluated the dietary intake, growth pattern and risk of
      metabolic complications like dyslipidemia and insulin resistance among ART-naive
      HIV-infected children (CLHIV). METHODS: CLHIV 2-12 years of age, at the time of
      initiating ART in Chennai and Bangalore, were assessed for their dietary intake,
      anthropometry, blood CD4 cell count, HIV-1 viral load, fasting serum lipids,
      glucose and insulin. Homeostatic model assessment-insulin resistance was derived.
      RESULTS: Three hundred and ninety CLHIV (mean age [SD]: 8 [3] yrs; median viral
      load: 141,000 [25,876-436,000] copies/mL) were started on non-nucleoside reverse
      transcriptase inhibitor-based ART. Perinatal infection was documented among 97%.
      Sixty percent of children were in stage 3 or 4 of World Health Organization
      clinical staging of HIV/AIDS. Food insecurity was seen in 40% of households. A
      total of 204 children (52.4%) were stunted and 224 (57.6%) were underweight.
      Stunting seemed to be more prevalent with increasing age (0-4 years: 48%; >9
      years: 60%). Mean intakes of calories, iron, folate and calcium were
      significantly less than recommended dietary allowances across all age groups.
      Dyslipidemia, in terms of any abnormal triglycerides or total cholesterol or low
      density lipoprotein cholesterol (excluding high-density lipoprotein cholesterol),
      was seen in approximately 40% of children; insulin resistance in 17%; and C
      reactive protein in risk range of metabolic syndrome in 24% of children.
      CONCLUSIONS: In the background of high food insecurity and malnutrition,
      cardiometabolic abnormalities were seen in 20%-35% of ART-naive CLHIV in India
      emphasizing close monitoring of these children for long-term cardiovascular
      morbidities after initiation of ART.

PMID- 29189658
TI  - Discharge Criteria for Bronchiolitis: An Unmet Need.
AB  - BACKGROUND: Admission criteria and standardized management strategies for
      bronchiolitis are addressed in several guidelines and have shown to be
      beneficial; however, guidance regarding discharge criteria is limited and widely
      variable. We assessed the impact on clinical outcomes of a discharge protocol for
      children <2 years of age hospitalized with bronchiolitis in a tertiary care
      pediatric hospital. METHODS: In October 2013, a protocol to standardize the
      discharge of children with bronchiolitis was implemented in the infectious
      diseases (ID) ward but not in other pediatric units caring for these children
      (non-ID). The protocol included objective clinical criteria and a standardized
      oxygen weaning pathway. Patients were identified via International Classification
      of Diseases-9 codes and data manually reviewed. We compared length of stay (LOS)
      and readmission rates within 2 weeks of discharge according to protocol
      implementation (ID versus non-ID), adjusted for demographic factors,
      comorbidities, viral etiology and stratified by pediatric intensive care unit
      admission. RESULTS: From October 2013 to May 2015, 1118 children were
      hospitalized in ID and 695 in non-ID units. Median age was 4.5 months, 55% were
      males and 28% had comorbidities. LOS was 36% longer in non-ID units (risk ratio:
      1.36 [1.27-1.45]; P < 0.001) adjusted for age, gender, comorbidities and viral
      etiology. Difference in LOS remained significant after excluding children with
      comorbidities and stratifying by pediatric intensive care unit admission.
      Readmission rates were comparable between units (ID, 2.9% versus non-ID, 2.6%).
      CONCLUSIONS: A standardized discharge protocol for bronchiolitis reduced LOS
      without increasing readmission rates. Unifying bronchiolitis discharge criteria
      and oxygen weaning pathways could positively impact hospital-based patient care
      for this condition.

PMID- 29189660
TI  - Atraumatic Liver Retraction Using Nelaton Catheters During Totally Laparoscopic
      Gastrectomy.
AB  - This study introduces a novel technique for liver retraction during laparoscopic
      gastrectomy and assesses its impact on postoperative recovery. This study
      included 139 patients in whom Nelaton catheters (n=57) or Nathanson retractors
      (n=82) were used for liver retraction. Serum liver enzyme levels were measured
      preoperatively and on the first, second, third, fifth, and seventh postoperative
      days. Clinicopathologic features and postoperative recovery variables between the
      2 groups were compared. The aspartate aminotransferase, alanine aminotransferase,
      and C-reactive protein levels were significantly lower (P<0.001, P<0.001, and
      P=0.007, respectively), and the day of first flatus, the day of initiating a soft
      diet, and the length of hospital stay were shorter in the Nelaton catheter U
      shaped retractor group than those seen in the Nathanson retractor group (P=0.035,
      P=0.002, and P=0.024, respectively). Atraumatic liver retraction with Nelaton
      catheters is recommended in laparoscopic gastrectomy.

PMID- 29189661
TI  - Laparoscopic Versus Open Distal Pancreatectomy: Comparative Analysis of Clinical
      Outcomes at a Single Institution.
AB  - PURPOSE: Undertake a comparison between laparoscopic distal pancreatectomy (LDP)
      and open distal pancreatectomy (ODP) for the management of benign and malignant
      lesions. METHODS: A case series study of 93 consecutive patients subjected to a
      distal pancreatectomy for pancreatic tumors between 2001 and 2015. In each
      patient, clinical and surgical characteristic, postoperative course,
      histopathologic examination, and survival were analyzed. RESULTS: LDP was
      associated with significantly less operative blood loss (50 mL vs. 300 mL;
      P<0.01), higher spleen preservation rate (52.6% vs. 19.2%; P<0.01) and shorter
      hospital stay (5 d vs. 8 d; P<0.01). In patients with adenocarcinoma, survival at
      1 and 5 years were 63.5% and 15.9% in the ODP group versus 66.7% and 33.3% in the
      LDP group (P=0.43). CONCLUSIONS: LDP is a safe and feasible procedure for DP
      resections. LDP offers advantages over ODP in terms of reduction of operative
      blood loss, higher spleen preservation rate, and shorter hospital stay.

PMID- 29189662
TI  - Does Peritoneal Suction Drainage Reduce Pain After Gynecologic Laparoscopy?
AB  - This study evaluated the effect of drain placement on pain intensity after
      gynecologic laparoscopy. This study enrolled 120 patients with benign gynecologic
      lesions who underwent laparoscopic surgery. Patients were randomly divided into a
      standard group or the modified group. The modified group received suction drains
      that remained in place until 12 hours after surgery. We assessed patients' mean
      pain scores according to a visual analog scale at 12 and 24 hours after surgery.
      The mean pain score in the modified group was 6.01+/-1.96 at 12 hours after
      surgery and 3.86+/-1.57 at 24 hours after surgery. The standard group had a mean
      pain score of 5.43+/-1.7 at 12 hours after surgery and 3.51+/-1.27 at 24 hours
      after surgery. These findings did not significantly differ (P=0.6) even though
      the mean dose of parenteral analgesia was 0.68+/-0.83 in the standard group and
      0.41+/-0.67 in the modified group (P=0.05). We observed no differences in
      complications and hospital stay between the groups. The data suggest that
      drainage may not reduce postoperative pain and should be used in its traditional
      role for potential bleeding or infections.

PMID- 29189663
TI  - Decrease of Sphincter Preserving Length Lowers the Postoperative Genital Function
      for Patients With Rectal Cancer.
AB  - BACKGROUND AND OBJECTIVE: With the increase in sphincter preserving rate of
      rectal cancer (RC) cancer, postoperative quality-of-life, such as genital
      dysfunction, has become a major issue in the patient management. In this study,
      we proposed a measurement, namely, the sphincter preserving length (SPL), and
      investigated the relationship between SPL and postoperative genital function and
      survival in RC patients. METHODS: A total of 536 male patients who had a
      diagnosis of RC and underwent sphincter preserving rectal resection in the Sixth
      Affiliated Hospital of Sun Yat-sen University and the First Affiliated Hospital
      of Sun Yat-sen University between October 1997 and December 2013 were included in
      our study. SPL was defined as the distance between the lowest edge of the tumor
      to dentate line. Postoperative genital function was evaluated by erection
      function and ejaculation function. Five-year survival status was extracted from
      the hospital database. RESULTS: Larger SPL was significantly associated with
      poorer postoperative erection and ejaculation function. For a SPL of 7.25 cm, the
      sensitivity and specificity of the diagnosis of erection dysfunction was 68.6%
      and 68.8%, respectively. The corresponding sensitivity and specificity for the
      diagnosis of ejaculation dysfunction was 70.9% and 75.7%, respectively. SPL was
      also negatively associated with survival rate. Compared with lower anterior
      resection, patients with lower RC who underwent local resection or draw-out colon
      anal anastomosis had better postoperative genital function. CONCLUSIONS: SPL
      might be a useful measurement to assess the risk of postoperative genital
      dysfunction and survival status and an indicator for initiation of early
      preventative treatment in patients with RC.

PMID- 29189665
TI  - Therapeutic Drug Monitoring of Busulfan for the Management of Pediatric Patients:
      Cross-Validation of Methods and Long-Term Performance.
AB  - BACKGROUND: Busulfan (Bu) is an alkylating agent used as part of the conditioning
      regimen in pediatric patients before hematopoietic stem cell transplantation.
      Despite intravenous (IV) administration and dosing recommendations based on age
      and weight, reports have revealed interindividual variability in Bu
      pharmacokinetics and the outcomes of hematopoietic stem cell transplantation. In
      this context, adjusting doses to Bu's narrow therapeutic window is advised. We
      aimed to assess the utility of therapeutic drug monitoring (TDM) of Bu in
      children, the reliability of Bu quantification methods, and its stability in
      plasma when stored for up to 5 years. METHODS: Eighteen patients from our TDM
      center (252 samples) were included. All of them received a 2-hour Bu IV infusion
      4 times daily for a total of 16 doses. The first dose of Bu was age/weight-based,
      and the subsequent doses were adjusted from third or fifth dose onward based on
      the estimated first dose pharmacokinetic parameters to target steady-state
      concentrations (Css) of 600-900 ng/mL. The performance of our unit's high
      performance liquid chromatography with tandem mass spectrometry method was
      assessed using a quality control (QC, 35 series) chart. International,
      multicenter, cross-validation test (n = 21) was conducted to validate different
      analytical methods. To assess Bu stability, regression analyses and Bland-Altman
      plots were performed on measurements at repeated time points on samples stored at
      -80 degrees C for up to 5 years. RESULTS: We observed a 4.2-fold interindividual
      variability in Bu Css after the first dose, with only 28% of children having a
      Css within the target range. During the 4 days of conditioning, 83% of children
      had their doses modified according to TDM recommendations. This achieved a Css
      within the target range in 75% of the children. Routine QC measurements were
      generally within the +/-15% range around theoretical values, showing the optimal
      robustness of our center's analytical method. Two of the 21 Bu TDM centers
      returned inadequate results during cross-validation testing; both used a UV
      detection method. Storage at -80 degrees C led to a fall in Bu content of 14.9%
      +/- 13.4% at 2-4 years and of 20% +/- 5% by 5 years (roverall = 0.92).
      CONCLUSIONS: We conclude that TDM is an effective method of achieving targeted Bu
      levels in children. QC programs are crucial to monitoring and maintaining the
      quality of an analytical method.

PMID- 29189664
TI  - Early Therapeutic Drug Monitoring of Posaconazole Oral Suspension in Patients
      With Hematologic Malignancies.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) of posaconazole is usually
      performed 1 week after starting the drug because of its long half-life. However,
      previous studies showed that measuring the posaconazole plasma concentration
      (PPC) on day 3 is effective for predicting steady-state levels. The purpose of
      this study was to evaluate the relevance of early TDM (day 3) of posaconazole for
      achieving an optimal PPC. METHODS: This prospective study was conducted from
      September 2014 to August 2016. A total of 148 patients with acute myeloid
      leukemia or myelodysplastic syndromes received a 200 mg posaconazole oral
      suspension 3 times daily for fungal prophylaxis. During the period from September
      2014 to December 2015 (control group), no dose adjustment was performed on day 3.
      During the period from January 2016 to Aug 2016 (early TDM group), the frequency
      of posaconazole 200-mg administration was increased to 4 times daily in patients
      whose PPC on day 3 was <400 ng/mL. The cutoff value for optimal PPC on day 8 was
      defined as 500 ng/mL. RESULTS: In 21 of 107 patients (20%) in the control group,
      PPC was <400 ng/mL on day 3. In 15 (71%) of these 21 patients, the PPC was
      suboptimal on day 8. In the early TDM group, the PPC was <400 ng/mL on day 3 in 4
      of 41 patients (10%). After increasing the posaconazole administration frequency
      in these 4 patients, PPC was suboptimal on day 8 in 1 patient (25%). In both
      groups, 104 patients had a PPC of >=500 ng/mL on day 3, but 7% (7/104) of these
      had a suboptimal level on day 8. CONCLUSIONS: Early TDM on day 3 for posaconazole
      suspension may help more patients achieve optimal drug levels on day 8, although
      TDM on day 8 is needed even in patients with optimal levels on day 3.

PMID- 29189666
TI  - Validity of Wearable Activity Monitors during Cycling and Resistance Exercise.
AB  - INTRODUCTION: The use of wearable activity monitors has seen rapid growth;
      however, the mode and intensity of exercise could affect the validity of heart
      rate (HR) and caloric (energy) expenditure (EE) readings. There is a lack of data
      regarding the validity of wearable activity monitors during graded cycling
      regimen and a standard resistance exercise. The present study determined the
      validity of eight monitors for HR compared with an ECG and seven monitors for EE
      compared with a metabolic analyzer during graded cycling and resistance exercise.
      METHODS: Fifty subjects (28 women, 22 men) completed separate trials of graded
      cycling and three sets of four resistance exercises at a 10-repetition-maximum
      load. Monitors included the following: Apple Watch Series 2, Fitbit Blaze, Fitbit
      Charge 2, Polar H7, Polar A360, Garmin Vivosmart HR, TomTom Touch, and Bose
      SoundSport Pulse (BSP) headphones. HR was recorded after each cycling intensity
      and after each resistance exercise set. EE was recorded after both protocols.
      Validity was established as having a mean absolute percent error (MAPE) value of
      <=10%. RESULTS: The Polar H7 and BSP were valid during both exercise modes
      (cycling: MAPE = 6.87%, R = 0.79; resistance exercise: MAPE = 6.31%, R = 0.83).
      During cycling, the Apple Watch Series 2 revealed the greatest HR validity (MAPE
      = 4.14%, R = 0.80). The BSP revealed the greatest HR accuracy during resistance
      exercise (MAPE = 6.24%, R = 0.86). Across all devices, as exercise intensity
      increased, there was greater underestimation of HR. No device was valid for EE
      during cycling or resistance exercise. CONCLUSIONS: HR from wearable devices
      differed at different exercise intensities; EE estimates from wearable devices
      were inaccurate. Wearable devices are not medical devices, and users should be
      cautious when using these devices for monitoring physiological responses to
      exercise.

PMID- 29189667
TI  - Repeatability and Meaningful Change of CPET Parameters in Healthy Subjects.
AB  - INTRODUCTION/PURPOSE: Cardiopulmonary exercise testing (CPET) plays an important
      role in clinical medicine and research. Repeatability of CPET parameters has not
      been well characterized, but is important to assess variability and determine if
      there have been meaningful changes in a given CPET parameter. METHODS: We
      recruited 45 healthy subjects and performed two symptom-limited CPET within 30 d
      using a cycle ergometer. Differences in relevant CPET parameters between CPET-1
      and CPET-2 were assessed using a paired t-test. Coefficient of variation (CoV)
      and Bland-Altman plots are reported. Factors that may be associated with
      variability were analyzed (sex, age, time of day, fitness level). The coefficient
      of repeatability was calculated for peak oxygen consumption (VO2) and VO2 at
      lactate threshold (LT) to establish a 95% threshold for meaningful change.
      RESULTS: There were no significant differences between tests in the parameters
      reported. Specifically, we found overall low CoV in peak VO2 (4.9%), VO2@LT
      (10.4%), peak O2 pulse (4.6%), peak minute ventilation (VE; 7.4%), VE/VCO2@LT
      (4.0%), and VE/VO2@LT (4.8%). The CoV for peak respiratory exchange ratio@LT was
      significantly affected by diurnal factors; age, sex, and fitness level did not
      affect variability. The 95% threshold for meaningful change was 0.540 L.min in
      peak VO2 and 0.520 L.min in VO2@LT. CONCLUSIONS: Repeatability of CPET parameters
      is generally higher than previously reported. There were no significant
      differences in variability related to sex, age, and fitness level; diurnal
      factors had a limited effect. The threshold for meaningful change in peak VO2 and
      for VO2@LT should be considered when gauging a response to therapies or training.

PMID- 29189668
TI  - The Role of Airway Inflammation and Bronchial Hyperresponsiveness in Athlete's
      Asthma.
AB  - PURPOSE: Asthma is frequently reported in endurance athletes. The aim of the
      present study was to assess the long-term airway inflammatory response to
      endurance exercise in high-level athletes with and without asthma. METHODS: In a
      cross-sectional design, 20 asthmatic athletes (10 swimmers and 10 cross-country
      skiers), 19 athletes without asthma (10 swimmers and 9 cross-country skiers), and
      24 healthy nonathletes completed methacholine bronchial challenge, lung function
      tests, and sputum induction on two separate days. All athletes competed on a
      national or international level and exercised >=10 h.wk. The nonathletes
      exercised <=5 h.wk and reported no previous lung disease. Bronchial
      hyperresponsiveness (BHR) was defined as a methacholine provocation dose causing
      20% decrease in the forced expiratory volume in 1 s of <=8 MUmol. RESULTS: BHR
      was present in 13 asthmatic athletes (62%), 11 healthy athletes (58%), and 8
      healthy nonathletes (32%), and the prevalence differed among groups (P = 0.005).
      Sputum inflammatory and epithelial cell counts did not differ between groups and
      were within the normal range. Median (25th to 75th percentiles) sputum
      interleukin-8 was elevated in both asthmatic (378.4 [167.0-1123.4]) and healthy
      (340.2 [175.5-892.4]) athletes as compared with healthy nonathletes (216.6 [129.5
      314.0], P = 0.02). No correlations were found between provocation dose causing
      20% decrease and sputum cell counts. CONCLUSION: Independent of asthma diagnosis,
      a high occurrence of BHR and an increased sputum interleukin-8 were found in
      athletes as compared with nonathletes. Airway inflammation or epithelial damage
      was not related to BHR.

PMID- 29189669
TI  - Measurement of Dead Space Fraction Upon ICU Admission Predicts Length of Stay and
      Clinical Outcomes Following Bidirectional Cavopulmonary Anastomosis.
AB  - OBJECTIVES: Increased alveolar dead space fraction has been associated with
      prolonged mechanical ventilation and increased mortality in pediatric patients
      with respiratory failure. The association of alveolar dead space fraction with
      clinical outcomes in patients undergoing bidirectional cavopulmonary anastomosis
      for single ventricle congenital heart disease has not been reported. We describe
      an association of alveolar dead space fraction with postoperative outcomes in
      patients undergoing bidirectional cavopulmonary anastomosis. DESIGN: In a
      retrospective case-control study, we examined for associations between alveolar
      dead space fraction ([PaCO2 - end-tidal CO2]/PaCO2), arterial oxyhemoglobin
      saturation, and transpulmonary gradient upon postoperative ICU admission with a
      composite primary outcome (requirement for surgical or catheter-based
      intervention, death, or transplant prior to hospital discharge, defining cases)
      and several secondary endpoints in infants following bidirectional cavopulmonary
      anastomosis. SETTINGS: Cardiac ICU in a tertiary care pediatric hospital.
      PATIENTS: Patients undergoing bidirectional cavopulmonary anastomosis at our
      institution between 2011 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Of 191 patients undergoing bidirectional cavopulmonary anastomosis, 28
      patients were cases and 163 were controls. Alveolar dead space fraction was
      significantly higher in the case (0.26 +/- 0.09) versus control group (0.17 +/-
      0.09; p < 0.001); alveolar dead space fraction at admission was less than 0.12 in
      0% of cases and was greater than 0.28 in 35% of cases. Admission arterial
      oxyhemoglobin saturation was significantly lower in the case (77% +/- 12%) versus
      control group (83% +/- 9%; p < 0.05). Sensitivity and specificity for future case
      versus control assignment was best when prebidirectional cavopulmonary
      anastomosis risk factors, admission alveolar dead space fraction (AUC, 0.74), and
      arterial oxyhemoglobin saturation (AUC, 0.65) were combined in a summarial model
      (AUC, 0.83). For a given arterial oxyhemoglobin saturation, the odds of becoming
      a case increased on average by 181% for every 0.1 unit increase in alveolar dead
      space fraction. Admission alveolar dead space fraction and arterial oxyhemoglobin
      saturation were linearly associated with prolonged ICU length of stay, hospital
      length of stay, duration of mechanical ventilation, and duration of thoracic
      drainage (p < 0.001 for all). CONCLUSIONS: Following bidirectional cavopulmonary
      anastomosis, alveolar dead space fraction in excess of 0.28 or arterial
      oxyhemoglobin saturation less than 78% upon ICU admission indicates an increased
      likelihood of requiring intervention prior to hospital discharge. Increasing
      alveolar dead space fraction and decreasing arterial oxyhemoglobin saturation are
      associated with increased lengths of stay.

PMID- 29189670
TI  - Psychological and Psychiatric Outcomes Following PICU Admission: A Systematic
      Review of Cohort Studies.
AB  - OBJECTIVE: Admissions to PICU places pediatric patients at increased risk of
      persistent psychological and psychiatric morbidity. This systematic review aimed
      to summarize and critically examine literature regarding psychological and
      psychiatric outcomes of pediatric patients following PICU admission. DATA
      SOURCES: MEDLINE, Web of Science, Cochrane Library, Science Direct, PsycInfo,
      CINAHL, LILACS, and SciELO were searched up to May 2016. STUDY SELECTION: Cohort
      studies about psychological and psychiatric outcomes of pediatric patients
      following PICU admission; full-text records published in English, Spanish, or
      Portuguese in peer-reviewed journals from 2000 to 2015 were included. Neonatal
      patient population (age, <1 mo), follow-up after PICU discharge (<3 mo), and
      nonprimary literature were excluded. Two reviewers independently screened studies
      based on the predetermined exclusion criteria. DATA EXTRACTION: Data were
      extracted using an adapted tool. The internal validity and risk of bias were
      assessed using Newcastle-Ottawa Scale. DATA SYNTHESIS: The search yielded 1,825
      studies after the removal of duplications, of which eight met the inclusion
      criteria. Methodologic quality of the studies ranged from low to high, with an
      average score of five of nine. Of all the studies, half had a control group.
      Regarding the length of follow-up, most of the studies ranged from 3 to 12
      months. CONCLUSIONS: Psychological and psychiatric outcomes after pediatric
      critical illness appear to be substantial issues that need to be further studied.
      Our review highlights the need for psychological screening of pediatric patients
      and their parents following PICU admission since these patients are a vulnerable
      population at risk for developing psychiatric responses.

PMID- 29189671
TI  - Neural Breathing Pattern and Patient-Ventilator Interaction During Neurally
      Adjusted Ventilatory Assist and Conventional Ventilation in Newborns.
AB  - OBJECTIVE: To compare neurally adjusted ventilatory assist and conventional
      ventilation on patient-ventilator interaction and neural breathing patterns, with
      a focus on central apnea in preterm infants. DESIGN: Prospective, observational
      cross-over study of intubated and ventilated newborns. Data were collected while
      infants were successively ventilated with three different ventilator conditions
      (30 min each period): 1) synchronized intermittent mandatory ventilation (SIMV)
      combined with pressure support at the clinically prescribed, SIMV with baseline
      settings (SIMVBL), 2) neurally adjusted ventilatory assist, 3) same as SIMVBL,
      but with an adjustment of the inspiratory time of the mandatory breaths (SIMV
      with adjusted settings [SIMVADJ]) using feedback from the electrical activity of
      the diaphragm). SETTING: Regional perinatal center neonatal ICU. PATIENTS:
      Neonates admitted in the neonatal ICU requiring invasive mechanical ventilation.
      MEASUREMENTS AND MAIN RESULTS: Twenty-three infants were studied, with median
      (range) gestational age at birth 27 weeks (24-41 wk), birth weight 780 g (490
      3,610 g), and 7 days old (1-87 d old). Patient ventilator asynchrony, as
      quantified by the NeuroSync index, was lower during neurally adjusted ventilatory
      assist (18.3% +/- 6.3%) compared with SIMVBL (46.5% +/-11.7%; p < 0.05) and
      SIMVADJ (45.8% +/- 9.4%; p < 0.05). There were no significant differences in
      neural breathing parameters, or vital signs, except for the end-expiratory
      electrical activity of the diaphragm, which was lower during neurally adjusted
      ventilatory assist. Central apnea, defined as a flat electrical activity of the
      diaphragm more than 5 seconds, was significantly reduced during neurally adjusted
      ventilatory assist compared with both SIMV periods. These results were comparable
      for term and preterm infants. CONCLUSIONS: Patient-ventilator interaction appears
      to be improved with neurally adjusted ventilatory assist. Analysis of the neural
      breathing pattern revealed a reduction in central apnea during neurally adjusted
      ventilatory assist use.

PMID- 29189672
TI  - Invasive Haemophilus influenzae Serotype a Infection in Children: Clinical
      Description of an Emerging Pathogen-Alaska, 2002-2014.
AB  - BACKGROUND: Invasive infections from Haemophilus influenzae serotype a (Hia) have
      been reported with increasing frequency, especially among indigenous populations.
      However, there are limited population-based studies of clinical severity. We
      studied invasive Hia infections in Alaska to determine clinical characteristics,
      mortality and sequelae. METHODS: We defined an invasive Hia infection as the
      first detection of Hia from a usually sterile site in a child <10 years of age
      from Alaska. We identified cases using the Alaska Invasive Bacterial Diseases
      Surveillance System and reviewed medical charts up to 2 years after reported
      illness. RESULTS: We identified invasive Hia infections in 36 children, 28 (78%)
      <1 year old, 34 (94%) living in an Alaskan village and 25 (69%) without
      documented underlying illness. Overlapping clinical presentations included
      meningitis in 15 children (42%); bacteremia and pneumonia in 10 children (28%);
      and bone, joint or soft tissue infections in 10 children (22%). In 4 other
      children, no source of invasive infection was identified. Intensive care was
      provided for 11 children (31%); 12 children (33%) required surgical intervention.
      One year after infection, 4 children (11%) had died from Hia, and 5 children
      (14%) had ongoing neurologic sequelae. CONCLUSIONS: Invasive Hia infections in
      Alaska occurred predominantly in Alaska Native infants in rural communities.
      Although one-third of children had preexisting conditions, most cases occurred
      without known comorbidity. Clinical syndromes were frequently severe. One year
      after infection, 1 in 4 children had either died or had neurologic sequelae. An
      effective vaccine would prevent significant morbidity and mortality in affected
      populations.

PMID- 29189673
TI  - Rotavirus Genotypes Circulating in Brazil Before and After the National Rotavirus
      Vaccine Program: A Review.
AB  - BACKGROUND: Rotavirus vaccines created the opportunity to control diarrhea in
      children. We describe the rotavirus genotypes before and after the rotavirus
      vaccine introduction in Brazil. METHODS: We reviewed the distribution of
      rotavirus genotypes in Brazil before and after vaccine introduction by searching
      publication. RESULTS: Eighty-six studies reported 6884 (15.2%) rotavirus episodes
      among 45,305 children. Rotavirus caused 22.4% and 11.6% of cases before and after
      vaccine introduction. G1P[8], G9P[8] and G2P[4] heterotypic strains were most
      common before and after vaccine introduction. CONCLUSIONS: The vaccines may have
      selected heterotypic strains in this highly vaccinated population.

PMID- 29189674
TI  - Concurrent Community Transmission of Enterovirus D68 With Human Rhinoviruses and
      Respiratory Syncytial Virus Among Children in Sendai, Japan.
AB  - BACKGROUND: In the autumn of 2015, we experienced a surge in the number of
      pediatric cases of wheeze in our hospital, which was suspected to be caused by
      enterovirus (EV)-D68 transmission in the community. Thus, we implemented an ad
      hoc retrospective surveillance for EV-D68. METHODS: Patients <15 years of age
      with acute respiratory infection were eligible for inclusion in this study. All
      enrolled patients underwent virus detection test. Additionally, neutralization
      tests (NTs) were performed using the stored serum samples of the enrolled
      patients to compare the antigenicity of the virus isolated in this study with
      that isolated in 2010 and evaluate the anti-EV-D68 antibody prevalence. RESULTS:
      Respiratory syncytial virus (RSV) was the most commonly detected virus (35%),
      followed by EV-D68 (19%) and non-EV-D68 enteroviruses/human rhinoviruses (14%).
      Patients with EV-D68 infection had higher median age than those with RSV
      infection (P < 0.05). Moreover, patients with EV-D68 infection showed a higher
      expiratory wheeze prevalence than those with non-EV-D68 enterovirus/rhinovirus
      and RSV infections. The antigenicity of the isolate from the current study was
      similar to the virus that circulated in 2010. At the early study phase, children
      in our community did not have high NT titers, but the median log NT titer
      increased from 1.5 to 5 over time (P < 0.05). CONCLUSION: This study showed the
      concurrent circulation of EV-D68 with non-EV-D68 enteroviruses/rhinoviruses and
      RSV in infants and children in our community and captured the early stage of EV
      D68 transmission.

PMID- 29189675
TI  - Increasing Linezolid-resistant Enterococcus in a Children's Hospital.
AB  - We report a reduction in susceptibility to linezolid among Enterococcus isolates
      (98% in 2007 vs. 46% in 2014) in parallel with a 5-fold increase in linezolid
      use. A direct association could not be established as the majority of patients
      with linezolid nonsusceptible isolates did not have prior linezolid exposure.
      Nosocomial transmission of the nonsusceptible isolates could certainly have
      contributed.

PMID- 29189676
TI  - Disseminated Cryptococcosis With Severe Increased Intracranial Pressure
      Complicated With Cranial Nerve Palsy in a Child.
AB  - Cryptococcosis is less common in children than in adults but remains an important
      cause of pneumonia and meningoencephalitis in both immunocompromised and
      immunocompetent patients. Intracranial hypertension commonly complicates
      cryptococcal meningitis and may cause significant visual and neurologic morbidity
      and mortality. Early and aggressive management of intracranial hypertension in
      accordance with established guidelines reduces the risk of long-term
      complications and death. In this case report, we present a 12-year-old girl with
      cryptococcal meningitis, pneumonitis and dermatitis complicated with cranial
      nerve palsy and loss of vision. She was successfully treated with serial
      cerebrospinal fluid drainage, antifungal and interferon gamma therapy.

PMID- 29189677
TI  - Defining Study Outcomes That Better Reflect Individual Response to Treatment.
AB  - BACKGROUND: Most clinical trials comparing treatments evaluate the separate
      effects on each of several efficacy and toxicity outcomes. However, population
      averaged summary measures of treatment differences may not accurately reflect
      individual responses to treatment, and drawing conclusions about which treatment
      is "best" is straightforward if one treatment is superior across all outcomes,
      but challenging when this is not the case. METHODS: We created a study outcome
      based on expert opinion, which captures the risk/benefit profile of response to a
      treatment. Treatments were compared using this ordered outcome with standard
      statistical techniques. To illustrate the approach, we used as an example a study
      designed to evaluate initial antiretroviral therapy (ART) in human
      immunodeficiency virus-1-infected infants, in which results were contradictory
      across the study's primary and secondary efficacy and toxicity outcomes. The
      proposed risk/benefit outcome was evaluated retrospectively in each participant.
      RESULTS: In the International Maternal Pediatric Adolescent AIDS Clinical Trials
      P1060 study, one treatment regimen (lopinavir/ritonavir-based ART) was superior
      to the other (nevirapine-based ART) in reducing viral load (primary outcome) but
      inferior for immunologic and growth outcomes (important secondary outcomes in
      resource-limited settings). Treatment comparisons using the risk/benefit outcome
      indicated that the lopinavir/ritonavir-based ART regimen had a higher proportion
      of participants with the best overall response to treatment. Comparisons focusing
      on individual-level responses for the secondary outcomes also favored
      lopinavir/ritonavir-based ART, results that differed from the original population
      averaged analyses ones. CONCLUSIONS: Designing studies prospectively using
      risk/benefit outcomes focusing on an individual's responses to treatment more
      closely matches the needs of clinicians making decisions about how best to treat
      patients in clinical settings.

PMID- 29189679
TI  - Featured Articles for CME Credit December 2017.

PMID- 29189678
TI  - Attempting to validate the overtriage/undertriage matrix at a Level I trauma
      center.
AB  - BACKGROUND: The Optimal Resources Document mandates trauma activation based on
      injury mechanism, physiologic and anatomic criteria and recommends using the
      overtriage/undertriage matrix (Matrix) to evaluate the appropriateness of trauma
      team activation. The purpose of this study was to assess the effectiveness of the
      Matrix method by comparing patients appropriately triaged with those
      undertriaged. We hypothesized that these two groups are different, and Matrix
      does not discriminate the needs or outcomes of these different groups of
      patients. METHODS: Trauma registry data, from January 2013 to December 2015, at a
      Level I trauma center, were reviewed. Overtriage and undertriage rates were
      calculated by Matrix. Patients with Injury Severity Score (ISS) of 16 or greater
      were classified by activation level (full, limited, consultation), and triage
      category by Matrix. Patients in the limited activation and consultation groups
      were compared with patients with full activation by demographics, injuries,
      initial vital signs, procedures, delays to procedure, intensive care unit
      admission, length of stay, and mortality. RESULTS: Seven thousand thirty-one
      patients met activation criteria. Compliance with American College of Surgeons
      tiered activation criteria was 99%. The Matrix overtriage rate was 45% and
      undertriage was 24%. Of 2,282 patients with an ISS of 16 or greater, 1,026 were
      appropriately triaged (full activation), and 1,256 were undertriaged.
      Undertriaged patients had better Glasgow Coma Scale score, blood pressure, and
      base deficit than patients with full activation. Intensive care unit admission,
      hospital stays, and mortality were lower in the undertriaged group. The
      undertriaged group required fewer operative interventions with fewer delays to
      procedure. CONCLUSION: Despite having an ISS of 16 or greater, patients with
      limited activations were dissimilar to patients with full activation. Level of
      activation and triage are not equivalent. The American College of Surgeons
      Committee on Trauma full and tiered activation criteria are a robust means to
      have the appropriate personnel present based on the available prehospital
      information. Evaluation of the process of care, regardless of level of
      activation, should be used to evaluate trauma center performance. LEVEL OF
      EVIDENCE: Therapeutic and care management, level III.

PMID- 29189681
TI  - Placental Abruption With Delayed Fetal Compromise in Maternal Acetaminophen
      Toxicity.

PMID- 29189682
TI  - In Reply.

PMID- 29189683
TI  - Tranexamic Acid for the Management of Obstetric Hemorrhage.

PMID- 29189684
TI  - In Reply.

PMID- 29189685
TI  - Comparison of Subcuticular Suture Type for Skin Closure After Cesarean Delivery:
      A Randomized Controlled Trial.

PMID- 29189686
TI  - In Reply.

PMID- 29189687
TI  - In Reply.

PMID- 29189691
TI  - Practice Bulletin No. 187 Summary: Neural Tube Defects.
AB  - Neural tube defects (NTDs) are congenital structural abnormalities of the central
      nervous system and vertebral column. Neural tube defects may occur as an isolated
      malformation, in combination with other malformations, as part of a genetic
      syndrome, or as a result of teratogenic exposure (1). Neural tube defects are the
      second-most-common major congenital anomaly (2) after cardiac malformations, and
      their prevalence varies by geographic region, race, and environmental factors
      (3). Outcomes and disabilities depend on level and extent of lesion; for
      instance, anencephaly is incompatible with life but most infants with spina
      bifida will survive after surgical repair (4). Importantly, and in contrast to
      many other congenital abnormalities, primary prevention of NTDs is possible with
      folic acid. In addition, prenatal screening and diagnosis are widely available,
      and fetal surgery has improved outcomes for some newborns. The purpose of this
      document is to provide information about NTDs and make management recommendations
      for the pregnancy complicated by a fetal NTD.

PMID- 29189692
TI  - Committee Opinion No. 726 Summary: Hospital Disaster Preparedness for
      Obstetricians and Facilities Providing Maternity Care.
AB  - Large-scale catastrophic events and infectious disease outbreaks highlight the
      need for disaster planning at all community levels. Features unique to the
      obstetric population (including antepartum, intrapartum, postpartum and neonatal
      care) warrant special consideration in the event of a disaster. Pregnancy
      increases the risks of untoward outcomes from various infectious diseases. Trauma
      during pregnancy presents anatomic and physiologic considerations that often can
      require increased use of resources such as higher rates of cesarean delivery.
      Recent evidence suggests that floods and human-influenced environmental disasters
      increase the risks of spontaneous miscarriages, preterm births, and low-birth
      weight infants among pregnant women. The potential surge in maternal and neonatal
      patient volume due to mass-casualty events, transfer of high-acuity patients, or
      redirection of patients because of geographic barriers presents unique challenges
      for obstetric care facilities. These circumstances require that facilities plan
      for additional increases in necessary resources and staffing. Although
      emergencies may be unexpected, hospitals and obstetric delivery units can prepare
      to implement plans that will best serve maternal and pediatric care needs when
      disasters occur. Clear designation of levels of maternal and neonatal care
      facilities, along with establishment of a regional network incorporating
      hospitals that provide maternity services and those that do not, will enable
      rapid transport of obstetric patients to the appropriate facilities, ensuring the
      right care at the right time. Using common terminology for triage and transfer
      and advanced knowledge of regionalization and levels of care will facilitate
      disaster preparedness.

PMID- 29189693
TI  - Practice Bulletin No. 187: Neural Tube Defects.
AB  - Neural tube defects (NTDs) are congenital structural abnormalities of the central
      nervous system and vertebral column. Neural tube defects may occur as an isolated
      malformation, in combination with other malformations, as part of a genetic
      syndrome, or as a result of teratogenic exposure (1). Neural tube defects are the
      second-most-common major congenital anomaly (2) after cardiac malformations, and
      their prevalence varies by geographic region, race, and environmental factors
      (3). Outcomes and disabilities depend on level and extent of lesion; for
      instance, anencephaly is incompatible with life but most infants with spina
      bifida will survive after surgical repair (4). Importantly, and in contrast to
      many other congenital abnormalities, primary prevention of NTDs is possible with
      folic acid. In addition, prenatal screening and diagnosis are widely available,
      and fetal surgery has improved outcomes for some newborns. The purpose of this
      document is to provide information about NTDs and make management recommendations
      for the pregnancy complicated by a fetal NTD.

PMID- 29189694
TI  - Committee Opinion No. 726: Hospital Disaster Preparedness for Obstetricians and
      Facilities Providing Maternity Care.
AB  - Large-scale catastrophic events and infectious disease outbreaks highlight the
      need for disaster planning at all community levels. Features unique to the
      obstetric population (including antepartum, intrapartum, postpartum and neonatal
      care) warrant special consideration in the event of a disaster. Pregnancy
      increases the risks of untoward outcomes from various infectious diseases. Trauma
      during pregnancy presents anatomic and physiologic considerations that often can
      require increased use of resources such as higher rates of cesarean delivery.
      Recent evidence suggests that floods and human-influenced environmental disasters
      increase the risks of spontaneous miscarriages, preterm births, and low-birth
      weight infants among pregnant women. The potential surge in maternal and neonatal
      patient volume due to mass-casualty events, transfer of high-acuity patients, or
      redirection of patients because of geographic barriers presents unique challenges
      for obstetric care facilities. These circumstances require that facilities plan
      for additional increases in necessary resources and staffing. Although
      emergencies may be unexpected, hospitals and obstetric delivery units can prepare
      to implement plans that will best serve maternal and pediatric care needs when
      disasters occur. Clear designation of levels of maternal and neonatal care
      facilities, along with establishment of a regional network incorporating
      hospitals that provide maternity services and those that do not, will enable
      rapid transport of obstetric patients to the appropriate facilities, ensuring the
      right care at the right time. Using common terminology for triage and transfer
      and advanced knowledge of regionalization and levels of care will facilitate
      disaster preparedness.

PMID- 29189695
TI  - Lymphoma Involving Skin and Subcutaneous Fat of the Breast: Two Cases.
AB  - Breast lymphoma is uncommon, and it usually involves breast parenchyma and
      ipsilateral axillary lymph nodes. We report rare cases of cutaneous T-cell
      lymphoma involving the skin and subcutaneous fat layers mimicking panniculitis of
      the breasts in a 33-year-old male patient who presented with a growing palpable
      mass and pain in both breasts and in 17-year-old female patient who presented
      with an indolent palpable breast mass for 1 year. Extranodal natural killer/T
      cell nasal-type and subcutaneous panniculitis-like T-cell lymphomas were
      diagnosed after skin punch biopsies. Here we report the clinical manifestations,
      mammographic and ultrasound findings, and the difficulties in histological
      diagnosis of the cases.

PMID- 29189700
TI  - Effectiveness of support groups to improve the quality of life of people with
      idiopathic pulmonary fibrosis a pre-post test pilot study.
AB  - BACKGROUND AND AIM OF THE WORK: Idiopathic Pulmonary Fibrosis (IPF) is an
      interstitial lung disease, which progressively leads to severe disability and
      death. The average survival expectancy, ranges from 3 to 5 years from diagnosis,
      and the available medicines do not lead to healing. The progression of IPF lead
      to a decline in forced vital capacity (FVC), dyspnea, cough, continuous sleep
      interruptions, resulting in increased fatigue and deteriorating quality of life
      (QOL), progressive limitation of daily life activities and social life, with
      repercussions on psychological and emotional well-being, aggravated by anxiety,
      loss of sense of self-confidence and depression. The aim of the study was to
      evaluate how the support groups influence the psychological well-being of people
      with IPF and their family members. METHODS: A pre-post test pilot study with a
      single group was conducted in a university hospital in Northern Italy, a centre
      for diagnosis and treatment of IPF. A support group was conducted by a nurse and
      entirely dedicated to people with IPF and their family members. Eighteen
      participants were enrolled in the support group. To measure the changes in
      psychological well-being was chosen the Psychological General Well-Being Index
      (PGWBI), which was administered at the time of enrolment to the group and after
      six months of attendance. RESULTS: Even if the effect is not statistically
      significant, the paired t-test showed that the participation in a support group
      conducted by a nurse, could increase psychological well-being in all of its
      dimensions: anxiety, depression, positivity, self-control, overall health, and
      vitality. CONCLUSIONS: Despite the null association, the increase of
      psychological well-being, closely related to the quality of life, indicates the
      need to further studies. In the absence of effective pharmacological treatments
      for healing, the support groups represent an opportunity for the wellbeing of the
      IPF patients and their caregivers.

PMID- 29189701
TI  - Expressive writing. A tool to help health workers. Research project on the
      benefits of expressive writing.
AB  - BACKGROUND AND AIMS: Numerous studies in the international literature hold that
      expressive writing is a useful tool to take care of the person as a whole. It
      gives voice to emotions, moods and intimate thoughts of patients, as well as
      caregivers and family members. The reference model is based on Pennebaker's
      theory (2004), which posits that expressing our deeper thoughts and feelings can
      result in significant health benefits in the short and long term. Studies over
      the past 25 years have shown that expressive writing, that is, simple writing on
      deeper thoughts and emotional sensations, is a useful tool to alleviate both
      physical and psychological symptoms. This research seeks to ascertain whether and
      how expressive writing has an impact on work satisfaction, coping strategies, and
      relational communication satisfaction of health practitioners. METHODS: a
      comparison was made between the expressive writing and neutral writing of two
      randomized groups of health care professionals. A group of 66 healthcare
      professionals participated in this study. They were evaluated pre- and post
      intervention using several scales and an ad hoc questionnaire, with one-month
      follow-up. RESULTS: After analyzing the texts, as in Pennebaker's studies, there
      was a reduction of words with negative emotion in the course of writing sessions.
      DISCUSSION: Expressive writing has a positive impact on adaptive coping
      strategies and work relational communication satisfaction. It also can facilitate
      the clarification and solution of various problems, increase cognitive abilities,
      and promote social interactions.

PMID- 29189702
TI  - Nurse training in self-management of patients with cardiovascular diseases: a
      multicentre observational study.
AB  - BACKGROUND AND AIM: The therapeutic education and self-management carried out by
      nurses, are winning elements in cardiovascular secondary prevention, but because
      they are complex matters, they require special training by the professionals. The
      target of the study has been to assess the effects in clinical practice of a
      training program for nurses in the management of patients with cardiovascular
      diseases, leaning towards a self-oriented patient management and therapeutic
      patient education. METHOD: The research utilized a quali-quantitative study to
      compare the responses of 53 trained nurses (experimental group) and 101 untrained
      nurses (control group). The instrument used was a self-report structured in two
      sections: the first, a qualitative kind, was used to investigate the portrayal of
      nurses regarding self-management; the second, a quantitative kind, included a
      Likert scale based on 5 points (1=never, 5=always) that investigated the
      professional nurse's action in its bio-psycho-socio-relational and clinical
      activities (La Sala, 2012). RESULTS: The trained nurses' approach is more
      oriented towards the psycho-socio-relational dimension, compared to the untrained
      nurses. A difference also emerged regarding activities of a bio clinical nature,
      which are performed much more by untrained nurses compared to trained
      professionals. CONCLUSIONS: The health education and self-management skills were
      used by trained nurses during their care of patients with cardiovascular
      diseases, stressing the importance for professional nurses to develop an
      integrated competence, using narrative talks as the main tool in a patient
      centred approach.

PMID- 29189703
TI  - The public perception of nurses. An Italian cross-sectional study.
AB  - BACKGROUND AND AIM: The public opinion about the nursing profession can influence
      health service users, the work performance of nurses, health policies, and the
      choice to become a nurse. The aim of this study was to investigate the perception
      of nursing in modern society. METHODS: A cross-sectional study was conducted with
      a sample of 398 participants belonging to four population groups: Very Important
      Persons (VIPs), general population, upper-school students, and nursing students.
      This phenomenon was assessed through the Nursing Attitude Questionnaire (NAQ) and
      several additional items. RESULTS: The results highlighted that general
      population and nursing students showed a significantly better image of nurses
      than did VIPs and upper-school students. CONCLUSIONS: Overall, the sample
      acknowledged nurses fundamental connotations and functions, although secondary
      school students poorly recognized nurses' professional autonomy, and VIPs'
      judgements seemed to be more sensitive to the image of nurses given by mass
      media.

PMID- 29189704
TI  - Preventing workplace incivility, lateral violence and bullying between nurses A
      narrative literature review.
AB  - : Introduction: according to available literature workplace incivility, lateral
      violence and bullying among nurses are widely diffused. Their negative
      consequences and the outcomes on nurses and healthcare organizations have been
      well described. However, real pro-active and reactive actions to manage these
      issues, seem to be poorly recognized and investigated. AIM: to summarize the
      results of international studies regarding the prevention of individual and
      collective reactions towards workplace incivility, lateral violence, and bullying
      between nurses. METHODS: a narrative literature review was performed. RESULTS: 7
      original papers were included in this review. The implementation of zero
      tolerance policies and passive dissemination of information about these phenomena
      showed to be clearly ineffective. CONCLUSIONS: The limited number of evidence
      based studies and the typologies of interventions (mainly educational rather than
      team building programs and assertive communication) show inadequate effectiveness
      plus a lacking in the scientific evidence-based support. The need to find out
      innovative and "creative" solutions to face these problems has been suggested by
      different authors.

PMID- 29189705
TI  - Validation of the Italian version of the Critical Pain Observation Tool in brain
      injured critically ill adults.
AB  - BACKGROUND AND AIM: Pain in intensive care units (ICUs) is a frequent and often
      undermanaged problem. Brain-injured patients are often unable to reliably self
      report their pain, calling forth the need to use behavioural scales such as the
      Critical-Care Pain Observation Tool (CPOT). This study aimed to test the
      reliability and validity of the Italian CPOT use with brain-injured ICU adults.
      METHOD: A sample of 50 adults critical care patients was included. Each patient
      was assessed by two independent observers at three predefined times - at rest;
      during mobilization for hygiene; 20 minutes later - using the CPOT, PAINAD, and
      NRS. RESULTS: A good correlation was found between independent observers scores
      during painful procedure, establishing interrater reliability of CPOT. Criterion
      validation was supported by a strong correlation between CPOT and PAINAD scores,
      and a moderate relation between CPOT and NRS scores. The CPOT was able to
      discriminate between patients undergoing painful versus non-painful procedures.
      However, PAINAD performed better in this sample, as revealed by the comparison
      between the two AUC of ROC curves. CONCLUSIONS: The Italian CPOT use was found
      reliable and valid in this patient group.

PMID- 29189706
TI  - Unplanned Extubations in Intensive Care Unit: evidences for risk factors. A
      literature review.
AB  - BACKGROUND AND AIM: Unplanned extubations (UE) are getting more and more relevant
      in Critical Care, becoming a quality and care safeness outcome. This happens
      because after an UE the patient can face some complications concerning the airway
      management, respiratory and hemodynamic problems, lengthen in the hospital stay
      and in the mechanical ventilation time.  The aim of this review is identify and
      classify the factors that could increase UE risk. METHODOLOGY: A systematic
      review of scientific articles was performed consulting the databases PubMed,
      Cinahl, Medline, EBSCOhost and Google Scholar. Articles from 2006 to 2011 were
      included. Pediatric Care settings were excluded. RESULTS: 21 articles were
      selected. From the results emerged that risk factors associated to the patient
      are widely controversial. Yet restlessness, a low level of sedation and a high
      level of consciousness seem to be highly related to UE. Organizational risk
      factors, as workload, nurse:patient ratio, and the use of interdisciplinary
      protocols seem to play an important role in UE. CONCLUSION: According the current
      literature, the research on UE still has to handle a wide uncertainty. There is
      the need for more studies developing conclusive evidences on the role of
      different risk factors. Anyway, literature highlights the importance of the nurse
      and of the healthcare system organization in reducing UE incidence.

PMID- 29189707
TI  - Management and effect of platelet-rich plasma on wound healing: small reality of
      Oglio Po Hospital.
AB  - Platelet Rich Plasma (PRP) represents a relatively new approach in regenerative
      medicine. Its use is increasing in the treatment of a variety of orthopedic
      conditions, such as the management of acute wounds, chronic non-healing lesions,
      acceleration of bone formation, tendinopathy and chondropathy. The Orthopaedic
      Unit at Oglio Po Hospital uses PRP Gel in wound care since 2008. More than 70
      patients have been treated with this procedure. The aim of this study is to show
      our patients outcome. We present 3 cases of severe traumatic wound treated with
      our PRP protocol. The patients had complete healing of the lesion with good
      aesthetic results.

PMID- 29189708
TI  - Comparative Analysis of Soybean Root Proteome Reveals Molecular Basis of
      Differential Carboxylate Efflux under Low Phosphorus Stress.
AB  - Carboxylate efflux from roots is a crucial and differential response of soybean
      genotypes to low phosphorus (P) stress. Exudation of carboxylic acids including
      oxalate, citrate, succinate and fumarate was induced under low P stress,
      particularly in P-efficient soybean genotypes. Enhancement of root length,
      surface area and volume further improved P acquisition under low P stress. To
      understand the molecular basis of carboxylate efflux under low P stress, the root
      proteome of contrasting genotypes (P-efficient: EC-232019 and P-inefficient: EC
      113396) was compared. Among a total of 325 spots, 105 (32%) were differentially
      abundant proteins (DAPs) between sufficient (250 uM) and low P (4 uM) levels.
      Abundance of 44 (14%) proteins decreased by more than two-fold under low P
      stress, while 61 (19%) proteins increased by more than two-fold. Protein
      identification and annotation revealed that the DAPs were involved in a myriad of
      functions including carboxylic acid synthesis, carbohydrate, protein and lipid
      metabolism. Proteins with significant abundance included malate dehydrogenase,
      isocitrate dehydrogenase, phosphoglucomutase, phosphoglycerate mutase,
      fructokinase, enolase, phosphoglycerate kinase, triosephosphate isomerase,
      alcohol dehydrogenase, glucan water dikinase, glutamine synthetase and
      argininosuccinate lyase. Inferences from proteomic analysis suggests the
      crosstalk between various metabolic pathways implicated in conferring superior P
      acquisition efficiency under stress.

PMID- 29189709
TI  - Non-Canonical Thinking for Targeting ALK-Fusion Onco-Proteins in Lung Cancer.
AB  - Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified in lung
      cancer at 3-7% frequency, thus representing an important subset of genetic
      lesions that drive oncogenesis in this disease. Despite the availability of
      multiple FDA-approved small molecule inhibitors targeting ALK fusion proteins,
      drug resistance to ALK kinase inhibitors is a common problem in clinic. Thus,
      there is an unmet need to deepen the current understanding of genomic
      characteristics of ALK rearrangements and to develop novel therapeutic strategies
      that can overcome ALK inhibitor resistance. In this review, we present the
      genomic landscape of ALK fusions in the context of co-occurring mutations with
      other cancer-related genes, pointing to the central role of genetic epistasis
      (gene-gene interactions) in ALK-driven advanced-stage lung cancer. We discuss the
      possibility of targeting druggable domains within ALK fusion partners in addition
      to available strategies inhibiting the ALK kinase domain directly. Finally, we
      examine the potential of targeting ALK fusion-specific neoantigens in combination
      with other treatments, a strategy that could open a new avenue for the improved
      treatment of ALK positive lung cancer patients.

PMID- 29189710
TI  - Non-Additive Transcriptomic Responses to Inoculation with Rhizobia in a Young
      Allopolyploid Compared with Its Diploid Progenitors.
AB  - Root nodule symbioses (nodulation) and whole genome duplication (WGD, polyploidy)
      are both important phenomena in the legume family (Leguminosae). Recently, it has
      been proposed that polyploidy may have played a critical role in the origin or
      refinement of nodulation. However, while nodulation and polyploidy have been
      studied independently, there have been no direct studies of mechanisms affecting
      the interactions between these phenomena in symbiotic, nodule-forming species.
      Here, we examined the transcriptome-level responses to inoculation in the young
      allopolyploid Glycine dolichocarpa (T2) and its diploid progenitor species to
      identify underlying processes leading to the enhanced nodulation responses
      previously identified in T2. We assessed the differential expression of genes
      and, using weighted gene co-expression network analysis (WGCNA), identified
      modules associated with nodulation and compared their expression between species.
      These transcriptomic analyses revealed patterns of non-additive expression in T2,
      with evidence of transcriptional responses to inoculation that were distinct from
      one or both progenitors. These differential responses elucidate mechanisms
      underlying the nodulation-related differences observed between T2 and the diploid
      progenitors. Our results indicate that T2 has reduced stress-related
      transcription, coupled with enhanced transcription of modules and genes
      implicated in hormonal signaling, both of which are important for nodulation.

PMID- 29189711
TI  - Early Postoperative Low Expression of RAD50 in Rectal Cancer Patients Associates
      with Disease-Free Survival.
AB  - BACKGROUND: Molecular biomarkers have the potential to predict response to the
      treatment of rectal cancer. In this study, we aimed to evaluate the prognostic
      and clinicopathological implication of RAD50 (DNA repair protein RAD50 homolog)
      expression in rectal cancer. METHODS: A total of 266 rectal cancer patients who
      underwent surgery and received chemo- and radiotherapy between 2000 and 2011 were
      involved in the study. Postoperative RAD50 expression was determined by
      immunohistochemistry in surgical samples (n = 266). RESULTS: Using Kaplan-Meier
      survival analysis, we found that low RAD50 expression in postoperative samples
      was associated with worse disease free survival (p = 0.001) and overall survival
      (p < 0.001) in early stage/low-grade tumors. In a comparison of patients with low
      vs. high RAD50 expression, we found that low levels of postoperative RAD50
      expression in rectal cancer tissues were significantly associated with perineural
      invasion (p = 0.002). CONCLUSION: Expression of RAD50 in rectal cancer may serve
      as a prognostic biomarker for long-term survival of patients with perineural
      invasion-positive tumors and for potential use in early stage and low-grade
      rectal cancer assessment.

PMID- 29189712
TI  - Genome-Wide Analysis Reveals the Secondary Metabolome in Streptomyces kanasensis
      ZX01.
AB  - Streptomyces kanasensis ZX01 produces some antibiotics and a glycoprotein with
      antiviral activity. To further evaluate its biosynthetic potential, here we
      sequenced the 7,026,279 bp draft genome of S. kanasensis ZX01 and analyzed all
      identifiable secondary gene clusters for controlling natural products. More than
      60 putative clusters were found in S. kanasensis ZX01, the majority of these
      biosynthetic loci are novel. In addition, the regulators for secondary metabolism
      in S. kanasensis ZX01 were abundant. The global regulator nsdA not only controls
      biosynthesis of some antibiotics, but also enhances production of glycoprotein GP
      1 with antiviral activity. This study importantly reveals the powerful interplay
      between genomic analysis and studies of traditional natural product
      purification/production increasing.

PMID- 29189713
TI  - Low Prevalence of Enzootic Equine Influenza Virus among Horses in Mongolia.
AB  - Horses are critically important for Mongolian herders' livelihoods, providing
      transportation and food products, and playing important cultural roles. Equine
      influenza virus (EIV) epizootics have been frequent among Mongolia's horses, with
      five occurring since 1970. We sought to estimate the prevalence for EIV infection
      among horses and Bactrian camels with influenza-like illness between national
      epizootics. In 2016-2017, active surveillance for EIV was periodically performed
      in four aimags (provinces). Nasal swabs were collected from 680 horses and 131
      camels. Seven of the horse swabs were "positive" for qRT-PCR evidence of
      influenza A (Ct value <= 38). Two more were "suspect positive" (Ct value > 38 and
      <= 40). These nine specimens were collected from four aimags. None of the camel
      specimens had molecular evidence of infection. Despite serial blind passage in
      Madin-Darby Canine Kidney cells (MDCK) cells, none of the nine horse specimens
      yielded an influenza A virus. None of the 131 herder households surveyed had
      recently vaccinated their horses against EIV. It seems likely that sporadic EIV
      is enzootic in multiple Mongolian aimags. This finding, the infrequent use of EIV
      vaccination, periodic prevalence of highly pathogenic avian influenza, and the
      mixing of domestic and wild equid herds suggest that Mongolia may be a hot spot
      for novel EIV emergence.

PMID- 29189714
TI  - The Morphologies of the Semiconductor Oxides and Their Gas-Sensing Properties.
AB  - Semiconductor oxide chemoresistive gas sensors are widely used for detecting
      deleterious gases due to low cost, simple preparation, rapid response and high
      sensitivity. The performance of gas sensor is greatly affected by the morphology
      of the semiconductor oxide. There are many semiconductor oxide morphologies,
      including zero-dimensional, one-dimensional, two-dimensional and three
      dimensional ones. The semiconductor oxides with different morphologies
      significantly enhance the gas-sensing performance. Among the various
      morphologies, hollow nanostructures and core-shell nanostructures are always the
      focus of research in the field of gas sensors due to their distinctive structural
      characteristics and superior performance. Herein the morphologies of
      semiconductor oxides and their gas-sensing properties are reviewed. This review
      also proposes a potential strategy for the enhancement of gas-sensing performance
      in the future.

PMID- 29189715
TI  - Microbial Risk Assessment of Tidal-Induced Urban Flooding in Can Tho City (Mekong
      Delta, Vietnam).
AB  - Public health risks from urban flooding are a global concern. Contaminated
      floodwater may expose residents living in cities as they are in direct contact
      with the water. However, the recent literature does not provide much information
      about this issue, especially for developing countries. In this paper, the health
      risk due to a flood event occurred in Can Tho City (Mekong Delta, Vietnam) on 7
      October 2013 was investigated. The Quantitative Microbial Risk Assessment method
      was used in this study. The data showed that the pathogen concentrations were
      highly variable during the flood event and exceeded water standards for surface
      water. Per 10,000 people in contact with the floodwater, we found Salmonella
      caused the highest number of infections to adults and children (137 and 374,
      respectively), while E. coli caused 4 and 12 cases, per single event,
      respectively. The results show that further investigations on health risk related
      to flood issues in Can Tho City are required, especially because of climate
      change and urbanization. In addition, activities to raise awareness- about
      floods, e.g., "living with floods", in the Mekong Delta should also consider
      health risk issues.

PMID- 29189717
TI  - Telomere Shortening in Hematological Malignancies with Tetraploidization-A
      Mechanism for Chromosomal Instability?
AB  - Aneuploidy, the presence of an abnormal number of chromosomes in a cell, is one
      of the most obvious differences between normal and cancer cells. There is,
      however, debate on how aneuploid cells arise and whether or not they are a cause
      or a consequence of tumorigenesis. Further, it is important to distinguish
      aneuploidy (the "state" of the karyotype) from chromosomal instability (CIN; the
      "rate" of karyotypic change). Although CIN leads to aneuploidy, not all aneuploid
      cells exhibit CIN. One proposed route to aneuploid cells is through an unstable
      tetraploid intermediate because tetraploidy promotes chromosomal aberrations and
      tumorigenesis. Tetraploidy or near-tetraploidy (T/NT) (81-103 chromosomes)
      karyotypes with or without additional structural abnormalities have been reported
      in acute leukemia, T-cell and B-cell lymphomas, and solid tumors. In solid tumors
      it has been shown that tetraploidization can occur in response to loss of
      telomere protection in the early stages of tumorigenesis in colon cancer,
      Barrett's esophagus, and breast and cervical cancers. In hematological
      malignancies T/NT karyotypes are rare and the role of telomere dysfunction for
      the induction of tetraploidization is less well characterized. To further our
      understanding of possible telomere dysfunction as a mechanism for
      tetrapolydization in hematological cancers we here characterized the chromosomal
      complement and measured the telomere content by interphase nuclei quantitative
      fluorescence in situ hybridization (iQFISH) in seven hematological cancer
      patients with T/NT karyotypes, and after cytogenetic remission. The patients were
      identified after a search in our local cytogenetic registry in the 5-year period
      between June 2012 and May 2017 among more than 12,000 analyzed adult patients in
      this period. One advantage of measuring telomere content by iQFISH is that it is
      a single-cell analysis so that the telomere content can be distinguished between
      normal karyotype cells and cells with T/NT karyotypes. We find that the telomeres
      are particularly short in cells with T/NT karyotypes as compared with normal
      cells, and in T/NT karyotypes harboring additional chromosomal aberrations as
      well. These findings suggest that telomere dysfunction in hematological
      malignancies may be a mechanism for tetraploidization and CIN.

PMID- 29189716
TI  - Recent Advances in Nucleic Acid Targeting Probes and Supramolecular Constructs
      Based on Pyrene-Modified Oligonucleotides.
AB  - In this review, we summarize the recent advances in the use of pyrene-modified
      oligonucleotides as a platform for functional nucleic acid-based constructs.
      Pyrene is of special interest for the development of nucleic acid-based tools due
      to its unique fluorescent properties (sensitivity of fluorescence to the
      microenvironment, ability to form excimers and exciplexes, long fluorescence
      lifetime, high quantum yield), ability to intercalate into the nucleic acid
      duplex, to act as a pi-pi-stacking (including anchoring) moiety, and others.
      These properties of pyrene have been used to construct novel sensitive
      fluorescent probes for the sequence-specific detection of nucleic acids and the
      discrimination of single nucleotide polymorphisms (SNPs), aptamer-based
      biosensors, agents for binding of double-stranded DNAs, and building blocks for
      supramolecular complexes. Special attention is paid to the influence of the
      design of pyrene-modified oligonucleotides on their properties, i.e., the
      structure-function relationships. The perspectives for the applications of pyrene
      modified oligonucleotides in biomolecular studies, diagnostics, and
      nanotechnology are discussed.

PMID- 29189718
TI  - Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the
      Structures Affect Cutaneous Absorption.
AB  - Flavonoids are bioactive phytochemicals that exhibit protective potential against
      cutaneous inflammation and photoaging. We selected eight flavonoid aglycones or
      glycosides to elucidate the chemistry behind their skin absorption capability
      through experimental and computational approaches. The skin delivery was
      conducted using nude mouse and pig skins mounted on an in vitro Franz cell
      assembly. The anti-inflammatory activity was examined using the O2*.

PMID- 29189720
TI  - Fabrication and Mechanical Behavior of Ex Situ Mg-Based Bulk Metallic Glass
      Matrix Composite Reinforced with Electroless Cu-Coated SiC Particles.
AB  - Magnesium-based bulk metallic glass matrix composites (BMGMCs) have better
      plasticity than the corresponding bulk metallic glasses (BMGs); however, their
      strength and density are often compromised due to the fact that the effective
      reinforcement phase is mostly plastic heavy metal. For lightweight SiC-particle
      reinforced BMGMCs, interface wettability and the sharpness of the particles often
      reduce the strengthening effect. In this work, SiC particles were coated with a
      thin Cu coating by electroless plating, and added to Mg54Cu26.5Ag8.5Gd11 melt in
      an amount of 5 wt % to prepare a BMGMC. The microstructure of the interface,
      mechanical behavior and fracture morphology of the BMGMC were studied by scanning
      electron microscopy and quasi-static compression testing. The results showed that
      the Cu coating improved the wettability between SiC and the matrix alloy without
      obvious interfacial reactions, leading to the dispersion of SiC particles in the
      matrix. The addition of Cu-coated SiC particles improved the plastic deformation
      ability of Mg54Cu26.5Ag8.5Gd11 BMG, proving that electroless plating was an
      effective method for controlling the interface microstructure and mechanical
      behavior of BMGMCs.

PMID- 29189719
TI  - Transcriptional and Hormonal Regulation of Weeping Trait in Salix matsudana.
AB  - Salix matsudana is a large and rapidly-growing tree, with erect or spreading
      branchlets (upright willow). However, S. matsudana var. pseudomatsudana is one of
      the varietas, with pendulous branchlets (weeping willow). It has high ornamental
      value for its graceful pendulous branches. In order to study the molecular basis
      for this weeping trait, leaves and stems collected at different developmental
      stages were analyzed using RNA-seq coupled with digital gene expression. Although
      weeping trees are used worldwide as landscape plants, little is known about the
      genes that control weeping. Our growth results indicated that branches in weeping
      willow developed and elongated throughout all developmental stages, but branches
      in upright willow grew rapidly in the initial stages and then grew slowly and
      began shoot branching in the middle stages. A total of 613 hormone-related genes
      were differentially expressed in willow development. Among these, genes
      associated with auxin and gibberellin (GA) were highly likely to be responsible
      for the weeping trait, and genes associated with auxin and ethylene probably play
      crucial roles in shoot elongation. The genes with differential expression
      patterns were used to construct a network that regulated stem development, and
      auxin-related genes were identified as hub genes in the network in the weeping
      willow. Our results suggest an important role of gibberellin and auxin in
      regulating the weeping trait in Salix matsudana. This is the first report on the
      molecular aspects of hormonal effects on weeping trait in willow using
      transcriptomics and helps in dissecting the molecular mechanisms by which the
      weeping trait is controlled.

PMID- 29189721
TI  - Evaluation of Surface Cleaning Procedures for CTGS Substrates for SAW Technology
      with XPS.
AB  - A highly efficient and reproducible cleaning procedure of piezoelectric
      substrates is essential in surface acoustic waves (SAW) technology to fabricate
      high-quality SAW devices, especially for new applications such SAW sensors
      wherein new materials for piezoelectric substrates and interdigital transducers
      are used. Therefore, the development and critical evaluation of cleaning
      procedures for each material system that is under consideration becomes crucial.
      Contaminants like particles or the presence of organic/inorganic material on the
      substrate can dramatically influence and alter the properties of the thin film
      substrate composite, such as wettability, film adhesion, film texture, and so on.
      In this article, focus is given to different cleaning processes like SC-1 and SC
      2, UV-ozone treatment, as well as cleaning by first-contact polymer Opticlean,
      which are applied for removal of contaminants from the piezoelectric substrate Ca
      3 TaGa 3 Si 2 O 14 . By means of X-ray photoelectron spectroscopy, the presence
      of the most critical contaminants such as carbon, sodium, and iron removed
      through different cleaning procedures were studied and significant differences
      were observed between the outcomes of these procedures. Based on these results, a
      two-step cleaning process, combining SC-1 at a reduced temperature at 30 ? C
      instead of 80 ? C and a subsequent UV-ozone cleaning directly prior to deposition
      of the metallization, is suggested to achieve the lowest residual contamination
      level.

PMID- 29189722
TI  - Using Spherical-Harmonics Expansions for Optics Surface Reconstruction from
      Gradients.
AB  - In this paper, we propose a new algorithm to reconstruct optics surfaces (aka
      wavefronts) from gradients, defined on a circular domain, by means of the
      Spherical Harmonics. The experimental results indicate that this algorithm
      renders the same accuracy, compared to the reconstruction based on classical
      Zernike polynomials, using a smaller number of polynomial terms, which
      potentially speeds up the wavefront reconstruction. Additionally, we provide an
      open-source C++ library, released under the terms of the GNU General Public
      License version 2 (GPLv2), wherein several polynomial sets are coded. Therefore,
      this library constitutes a robust software alternative for wavefront
      reconstruction in a high energy laser field, optical surface reconstruction, and,
      more generally, in surface reconstruction from gradients. The library is a
      candidate for being integrated in control systems for optical devices, or
      similarly to be used in ad hoc simulations. Moreover, it has been developed with
      flexibility in mind, and, as such, the implementation includes the following
      features: (i) a mock-up generator of various incident wavefronts, intended to
      simulate the wavefronts commonly encountered in the field of high-energy lasers
      production; (ii) runtime selection of the library in charge of performing the
      algebraic computations; (iii) a profiling mechanism to measure and compare the
      performance of different steps of the algorithms and/or third-party linear
      algebra libraries. Finally, the library can be easily extended to include
      additional dependencies, such as porting the algebraic operations to specific
      architectures, in order to exploit hardware acceleration features.

PMID- 29189724
TI  - Effects of Trimetaphosphate on Abiotic Formation and Hydrolysis of Peptides.
AB  - The primordial Earth probably had most of the factors needed for the emergence
      and development of life. It is believed that it had not only water, but also
      simple inorganic and organic materials. While studies since the 1950s on the
      origins of organic matter have established key roles for amino acids, conditions
      that would have promoted their condensation to make polymers, such as peptides or
      proteins, have yet to be fully defined. The condensation of amino acids in a
      water-rich environment is not thermodynamically favored. Therefore, the efficient
      formation of peptides requires the presence of a catalyst or the activation of a
      substrate. In living cells, the biosynthesis of proteins is assisted by enzymes
      and requires adenosine triphosphate (ATP), a relatively complex organic
      polyphosphate, which serves as an energy source. Outside the living organism,
      simpler inorganic polyphosphates can form active aminoacyl-phosphate anhydrides,
      which suggests the broader potential of phosphorus for enabling the
      polymerization of amino acids. However, this has yet to be demonstrated. To
      address this gap, aqueous solutions containing a simple dipeptide, diglycine, and
      a simple polyphosphate, trimetaphosphate, were dried, and reaction products were
      analyzed by high performance liquid chromatography and mass spectrometry (HPLC
      MS). Different reaction environments, which were defined by the initial solution
      composition, pH, temperature, and incubation time, were found to affect the
      distribution and yield of products. Our results collectively provide strong
      evidence for reactions that both condense and hydrolyze peptides. It is
      noteworthy that the co-occurrence of reactions that form and cleave peptides are
      a central feature of Kauffman's theory for the emergence of autocatalytic sets,
      which is a key step in the chemical origins of life.

PMID- 29189725
TI  - Laser Scanning Confocal Thermoreflectance Microscope for the Backside Thermal
      Imaging of Microelectronic Devices.
AB  - In this paper, we report on a confocal thermoreflectance imaging system that can
      examine the thermal characteristics of microelectronic devices by penetrating the
      backside of a device through the substrate. In this system, the local
      reflectivity variations due to heat generation in the device are measured point
      by point by a laser scanning confocal microscope capable of eliminating out-of
      focus reflections and the thermoreflectance is extracted via Fourier-domain
      signal processing. In comparison to the conventional widefield thermoreflectance
      microscope, the proposed laser scanning confocal thermoreflectance microscope
      improves the thermoreflectance sensitivity by ~23 times and the spatial
      resolution by ~25% in backside thermoreflectance measurements.

PMID- 29189723
TI  - Long Non-Coding RNAs in Metabolic Organs and Energy Homeostasis.
AB  - Single cell organisms can surprisingly exceed the number of human protein-coding
      genes, which are thus not at the origin of the complexity of an organism. In
      contrast, the relative amount of non-protein-coding sequences increases
      consistently with organismal complexity. Moreover, the mammalian transcriptome
      predominantly comprises non-(protein)-coding RNAs (ncRNA), of which the long
      ncRNAs (lncRNAs) constitute the most abundant part. lncRNAs are highly species-
      and tissue-specific with very versatile modes of action in accordance with their
      binding to a large spectrum of molecules and their diverse localization. lncRNAs
      are transcriptional regulators adding an additional regulatory layer in
      biological processes and pathophysiological conditions. Here, we review lncRNAs
      affecting metabolic organs with a focus on the liver, pancreas, skeletal muscle,
      cardiac muscle, brain, and adipose organ. In addition, we will discuss the impact
      of lncRNAs on metabolic diseases such as obesity and diabetes. In contrast to the
      substantial number of lncRNA loci in the human genome, the functionally
      characterized lncRNAs are just the tip of the iceberg. So far, our knowledge
      concerning lncRNAs in energy homeostasis is still in its infancy, meaning that
      the rest of the iceberg is a treasure chest yet to be discovered.

PMID- 29189726
TI  - Antifungal Activity and Action Mode of Cuminic Acid from the Seeds of Cuminum
      cyminum L. against Fusarium oxysporum f. sp. Niveum (FON) Causing Fusarium Wilt
      on Watermelon.
AB  - In order to develop a novel biofungicide, the antifungal activity and action mode
      of cuminic acid from the seed of Cuminum cyminum L. against Fusarium oxysporum f.
      sp. niveum (FON) on watermelon was determined systematically. In this study, the
      median effective concentration (EC50) value for cuminic acid in inhibiting
      mycelial growth of FON was 22.53 MUg/mL. After treatment with cuminic acid, the
      mycelial morphology was seriously influenced; cell membrane permeability and
      glycerol content were increased markedly, but pigment and mycotoxin (mainly
      fusaric acid) were significantly decreased. Synthesis genes of bikaverin (Bike1,
      Bike2 and Bike3) and fusaric acid (FUB1, FUB2, FUB3 and FUB4) both were
      downregulated compared with the control, as confirmed by quantitative RT-PCR. In
      greenhouse experiments, cuminic acid at all concentrations displayed significant
      bioactivities against FON. Importantly, significant enhancement of activities of
      SOD, POD, CAT and decrease of MDA content were observed after in vivo cuminic
      acid treatment on watermelon leaves. These indicated that cuminic acid not only
      showed high antifungal activity, but also could enhance the self-defense system
      of the host plant. Above all, cuminic acid showed the potential as a biofungicide
      to control FON.

PMID- 29189727
TI  - Staphylococcus aureus Bacteremia from Diffuse Muscular Infection Following
      Acupuncture Visualized by 18F-FDG PET/CT and MRI.
AB  - We describe the clinical course of a 60-year old male admitted with
      Staphylococcus aureus bacteremia and back-pain. The patient was suspected of
      having spondylitis and treated as such with antibiotics; however, both fluorine
      18 fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography and magnetic
      resonance imaging (MRI) with iv contrast showed significant inflammation of
      muscles and subcutaneous soft tissue in relation to the patients back and left
      shoulder, but no signs of the working diagnosis of spondylitis. The unusual
      location of the infection was not explained until a few days prior to being
      discharged when the patient reported visits to a local physiotherapist where he
      would have acupuncture performed for non-specific back pain. His last
      acupunctural procedure had been performed 6 days prior to admission. This case
      is, to our knowledge, the first to show muscular inflammation on both 18-F-FDG
      PET/CT and MRI following acupuncture due to S. aureus. This case highlights the
      need for clinicians to search for alternative explanations when imaging does not
      support the diagnosis.

PMID- 29189728
TI  - Proton Radiation Effects on Dark Signal Distribution of PPD CMOS Image Sensors:
      Both TID and DDD Effects.
AB  - Four-transistor (T) pinned photodiode (PPD) CMOS image sensors (CISs) with four
      megapixel resolution using 11um pitch high dynamic range pixel were radiated with
      3 MeV and 10MeV protons. The dark signal was measured pre- and post-radiation,
      with the dark signal post irradiation showing a remarkable increase. A
      theoretical method of dark signal distribution pre- and post-radiation is used to
      analyze the degradation mechanisms of the dark signal distribution. The
      theoretical results are in good agreement with experimental results. This
      research would provide a good understanding of the proton radiation effects on
      the CIS and make it possible to predict the dark signal distribution of the CIS
      under the complex proton radiation environments.

PMID- 29189729
TI  - Sugar-Sweetened Beverage Consumption and Risks of Obesity and Hypertension in
      Chinese Children and Adolescents: A National Cross-Sectional Analysis.
AB  - We investigated the consumption of sugar-sweetened beverage (SSB) and its
      association with obesity and hypertension in a national sample of children and
      adolescents in China, where many low- and middle-income families live. Data were
      obtained from a 2014 national intervention program against obesity in Chinese
      children and adolescents aged 6-17 years. Height, weight, waist circumference,
      and blood pressure were measured. Information of SSB consumption, socioeconomic
      status, dietary intake, screen time, and physical activity were self-reported.
      Multivariate logistic regression was used to assess the association of SSB
      consumption with obesity and hypertension. A total of 66.6% of the 53,151
      participants reported consuming SSB. The per capita and per consumer SSB intake
      were 2.84 +/- 5.26 servings/week and 4.26 +/- 5.96 servings/week, respectively.
      Boys, older children, and adolescents, and individuals with long screen time or
      high physical activity or low parental education level were more likely to
      consume SSB. Participants who were high SSB consumers had a higher odds ratio
      (1.133, 95% CI: 1.054-1.217) than non-consumers for having abdominal obesity
      after adjustment for age, sex, residence, socioeconomic status, diet, screen
      time, and physical activity. However, SSB consumption was not associated with
      general obesity or hypertension in children and adolescents. In conclusion, more
      than half of the children and adolescents in China consumed SSB, which was
      independently related to a high risk of abdominal obesity. The results of this
      study indicated that SSB reduction strategies and policies may be useful in
      preventing obesity among Chinese children and adolescents.

PMID- 29189730
TI  - A New Series of Pyrrole-Based Chalcones: Synthesis and Evaluation of
      Antimicrobial Activity, Cytotoxicity, and Genotoxicity.
AB  - In an effort to develop new potent antimicrobial and anticancer agents, new
      pyrrole-based chalcones were designed and synthesized via the base-catalyzed
      Claisen-Schmidt condensation of 2-acetyl-1-methylpyrrole with 5-(aryl)furfural
      derivatives. The compounds were evaluated for their in vitro antimicrobial
      effects on pathogenic bacteria and Candida species using microdilution and ATP
      luminescence microbial cell viability assays. MTT assay was performed to
      determine the cytotoxic effects of the compounds on A549 human lung
      adenocarcinoma, HepG2 human hepatocellular carcinoma, C6 rat glioma, and NIH/3T3
      mouse embryonic fibroblast cell lines. 1-(1-Methyl-1H-pyrrol-2-yl)-3-(5-(4
      chlorophenyl)furan-2-yl)prop-2-en-1-one (7) and 1-(1-methyl-1H-pyrrol-2-yl)-3-(5
      (2,5-dichlorophenyl)furan-2-yl)prop-2-en-1-one (9) were found to be the most
      potent antifungal agents against Candida krusei and therefore these compounds
      were chosen for flow cytometry analysis and Ames MPF assay. ATP bioluminescence
      assay indicated that the antifungal activity of compounds 7 and 9 against C.
      krusei was significantly higher than that of other compounds and the reference
      drug (ketoconazole), whereas flow cytometry analysis revealed that the percentage
      of dead cells treated with compound 7 was more than that treated with compound 9
      and ketoconazole. According to Ames MPF assay, compounds 7 and 9 were found to be
      non-genotoxic against TA98 and TA100 with/without metabolic activation. MTT assay
      indicated that 1-(1-methyl-1H-pyrrol-2-yl)-3-(5-(2-nitrophenyl)furan-2-yl)prop-2
      en-1-one (3) showed more selective anticancer activity than cisplatin against the
      HepG2 cell line. On the other hand, 1-(1-methyl-1H-pyrrol-2-yl)-3-(5-(4
      nitrophenyl)furan-2-yl)prop-2-en-1-one (1) was found to be more effective and
      selective on the A549 cell line than cisplatin.

PMID- 29189731
TI  - Differential Effects of Superoxide Dismutase Mimetics after Mechanical Overload
      of Articular Cartilage.
AB  - Post-traumatic osteoarthritis can develop as a result of the initial mechanical
      impact causing the injury and also as a result of chronic changes in mechanical
      loading of the joint. Aberrant mechanical loading initiates excessive production
      of reactive oxygen species, oxidative damage, and stress that appears to damage
      mitochondria in the surviving chondrocytes. To probe the benefits of increasing
      superoxide removal with small molecular weight superoxide dismutase mimetics
      under severe loads, we applied both impact and overload injury scenarios to
      bovine osteochondral explants using characterized mechanical platforms with and
      without GC4403, MnTE-2-PyP, and MnTnBuOE-2-PyP. In impact scenarios, each of
      these mimetics provides some dose-dependent protection from cell death and loss
      of mitochondrial content while in repeated overloading scenarios only MnTnBuOE-2
      PyP provided a clear benefit to chondrocytes. These results support the
      hypothesis that superoxide is generated in excess after impact injuries and
      suggest that superoxide production within the lipid compartment may be a critical
      mediator of responses to chronic overload. This is an important nuance
      distinguishing roles of superoxide, and thus superoxide dismutases, in mediating
      damage to cellular machinery in hyper-acute impact scenarios compared to chronic
      scenarios.

PMID- 29189732
TI  - Identification and Characterization of Hyphantria cunea Aminopeptidase N as a
      Binding Protein of Bacillus thuringiensis Cry1Ab35 Toxin.
AB  - The fall webworm, Hyphantria cunea (Drury) is a major invasive pest in China.
      Aminopeptidase N (APN) isoforms in lepidopteran larvae midguts are known for
      their involvement in the mode of action of insecticidal crystal (Cry) proteins
      from Bacillus thuringiensis. In the present work, we identified a putative Cry1Ab
      toxin-binding protein, an APN isoform designated HcAPN3, in the midgut of H.
      cunea by ligand blot and mass spectrometry. HcAPN3 was highly expressed
      throughout all larval developmental stages and was abundant in the midgut and
      hindgut tissues. HcAPN3 was down-regulated at 6 h, then was up-regulated
      significantly at 12 h and 24 h after Cry1Ab toxin treatment. We expressed HcAPN3
      in insect cells and detected its interaction with Cry1Ab toxin by ligand blot
      assays. Furthermore, RNA interference (RNAi) against HcAPN3 using oral delivery
      and injection of double-stranded RNA (dsRNA) resulted in a 61-66% decrease in
      transcript level. Down-regulating of the expression of HcAPN3 was closely
      associated with reduced susceptibility of H. cunea to Cry1Ab. In addition, the
      HcAPN3E fragment peptide expressed in Escherichia coli enhanced Cry1Ab toxicity
      against H. cunea larvae. This work represents the first evidence to suggest that
      an APN in H. cunea is a putative binding protein involved in Cry1Ab
      susceptibility.

PMID- 29189733
TI  - Surface Modification of Carbon Nanotubes with an Enhanced Antifungal Activity for
      the Control of Plant Fungal Pathogen.
AB  - The addition of surface functional groups to multi-walled carbon nanotubes
      (MWCNTs) expands their application in engineering, materials, and life science.
      In the study, we explored the antifungal activities of MWCNTs with different
      surface groups against an important plant pathogenic fungi Fusarium graminearum.
      All of the OH-, COOH-, and NH2-modified MWCNTs showed enhanced inhibition in
      spore elongation and germination than the pristine MWCNTs. The length of spores
      decreased by almost a half from 54.5 MUm to 28.3, 27.4, and 29.5 MUm, after being
      treated with 500 MUg.mL-1 MWCNTs-COOH, MWCNTs-OH, and MWCNTs-NH2 separately.
      Furthermore, the spore germination was remarkably inhibited by surface-modified
      MWCNTs, and the germination rate was only about 18.2%, three times lower than
      pristine MWCNTs. The possible antifungal mechanism of MWCNTs is also discussed.
      Given the superior antifungal activity of surface modified MWCNTs and the fact
      that MWCNTs can be mass-produced with facile surface modification at low cost, it
      is expected that this carbon nanomaterial may find important applications in
      plant protection.

PMID- 29189734
TI  - Fabrication and Characterization of Porous MgAl2O4 Ceramics via a Novel Aqueous
      Gel-Casting Process.
AB  - A novel and aqueous gel-casting process has been successfully developed to
      fabricate porous MgAl2O4 ceramics by using hydratable alumina and MgO powders as
      raw materials and deionized water as hydration agent. The effects of different
      amounts of deionized water on the hydration properties, apparent porosity, bulk
      density, microstructure, pore size distribution and compressive strength of the
      samples were investigated. The results indicated that the porosity and the
      microstructure of porous MgAl2O4 ceramics were governed by the amounts of
      deionized water added. The porous structure was formed by the liberation of
      physisorbed water and the decomposition of hydration products such as bayerite,
      brucite and boehmite. After determining the addition amounts of deionized water,
      the fabricated porous MgAl2O4 ceramics had a high apparent porosity (52.5-65.8%),
      a small average pore size structure (around 1-3 MUm) and a relatively high
      compressive strength (12-28 MPa). The novel aqueous gel-casting process with easy
      access is expected to be a promising candidate for the preparation of Al2O3-based
      porous ceramics.

PMID- 29189735
TI  - Effects of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation on
      Cardiovascular Mortality: The Importance of the Dose of DHA.
AB  - Recent evidence on the relationship between omega-3 long chain polyunsaturated
      fatty acid (n-3 LCPUFA) supplementation and cardiovascular health suggests that n
      3 LCPUFA may no longer be efficacious. This review summarises the randomised
      controlled trials (RCTs) that assess the effect of n-3 LCPUFA supplementation on
      cardiovascular mortality. It appears that in the RCTs that showed no effect of n
      3 LCPUFA on cardiovascular mortality, the dose of n-3 LCPUFA (in particular
      docosahexaenoic acid (DHA)) and hence the n-3 LCPUFA status, may not have been
      sufficiently high to demonstrate the efficacy, and/or the baseline n-3 LCPUFA
      status was already too high. The intention-to-treat analysis (ITT) is the gold
      standard for analysing RCTs and ITT is used for drug intervention trials where
      exposure to the drug versus no drug exposure provides two clearly distinct groups
      to determine the efficacy of the drug being studied. This differs in nutrition
      trials as often the nutrient of interest being studied is already being consumed
      by both groups (placebo and active) and therefore a true placebo group with
      absolutely no intake of the nutrient being studied is highly unlikely. Therefore,
      in n-3 LCPUFA supplementation trials, as there is no clear distinction between
      the two groups (placebo and n-3 LCPUFA), a per-protocol analysis (comparison of
      groups that includes only those participants that fully completed the original
      intervention allocation) should be conducted in addition to ITT analysis.
      Furthermore, blood analysis pre- and post-supplementation should be conducted to
      ensure that: (1) that the baseline n-3 status is not too high, in order to
      alleviate a potential ceiling effect; and (2) that the dose is high enough and
      hence the increase in omega-3 status will be high enough in order to assess the
      efficacy of n-3 LCPUFA supplementation.

PMID- 29189736
TI  - Acute Myeloid Leukaemia: New Targets and Therapies.
AB  - The most common acute hematological malignancy in adults is acute myeloid
      leukaemia (AML), accounting for more than 80% of cases in patients over 60 years
      of age [...].

PMID- 29189737
TI  - Novel Artificial Tears Containing Cross-Linked Hyaluronic Acid: An In Vitro Re
      Epithelialization Study.
AB  - Dry eye syndrome is a common disease which can damage the corneal epithelium. It
      is treated with eye drops to stimulate tear production and hydrate the corneal
      surface. The most prescribed artificial tear remedies contain hyaluronic acid
      (HA), which enhances epithelial wound healing, improving tissue health. To the
      best of our knowledge, only a few recent studies have investigated cross-linked
      HA (HA-CL) in eye drops for human applications. This work consists in an in vitro
      evaluation of the re-epithelialization ability of two different preparations
      containing a recently synthetized HA cross-linked with urea: 0.02% (w/v) HA-CL
      (solution 1, S1), and 0.4% (w/v) HA-CL (solution 2, S2). The study was conducted
      on both 2D human corneal cells (HCEpiC) and 3D reconstructed tissues of human
      corneal epithelium (HCE). Viability by 3(4,5-dimethylthiazol-2)2,5
      diphenyltetrazolium bromide (MTT) test, pro-inflammatory cytokine release
      (interleukin-8, IL-8) by ELISA, and morphology by hematoxylin and eosin (HE)
      staining were evaluated. In addition, to understand the molecular basis of the re
      epithelialization properties, cyclin D1 levels were assessed by western blot. The
      results showed no cellular toxicity, a slight decrease in IL-8 release, and
      restoration of epithelium integrity when the wounded 3D model was treated with S1
      and S2. In parallel, cyclin D1 levels increased in cells treated with both S1 and
      S2.

PMID- 29189739
TI  - Small Gold Nanorods: Recent Advances in Synthesis, Biological Imaging, and Cancer
      Therapy.
AB  - Over the past few decades, the synthetic development of ultra-small nanoparticles
      has become an important strategy in nano-medicine, where smaller-sized
      nanoparticles are known to be more easily excreted from the body, greatly
      reducing the risk caused by introducing nano-theranostic agents. Gold nanorods
      are one of the most important nano-theranostic agents because of their special
      optical and electronic properties. However, the large size (diameter > 6 nm) of
      most obtained gold nanorods limits their clinical application. In recent years,
      more and more researchers have begun to investigate the synthesis and application
      of small gold nanorods (diameter < 6 nm), which exhibit similar optical and
      electronic properties as larger gold nanorods. In this review, we summarize the
      recent advances of synthesis of the small gold nanorods and their application for
      near-infrared light-mediated bio-imaging and cancer therapy.

PMID- 29189738
TI  - Aging Gut Microbiota at the Cross-Road between Nutrition, Physical Frailty, and
      Sarcopenia: Is There a Gut-Muscle Axis?
AB  - Inadequate nutrition and physical inactivity are the mainstays of primary
      sarcopenia-physiopathology in older individuals. Gut microbiota composition is
      strongly dependent on both of these elements, and conversely, can also influence
      the host physiology by modulating systemic inflammation, anabolism, insulin
      sensitivity, and energy production. The bacterial metabolism of nutrients
      theoretically influences skeletal muscle cell functionality through producing
      mediators that drive all of these systemic effects. In this study, we review the
      scientific literature supporting the concept of the involvement of gut microbiota
      in primary sarcopenia physiopathology. First, we examine studies associating
      fecal microbiota alterations with physical frailty, i.e., the loss of muscle
      performance and normal muscle mass. Then, we consider studies exploring the
      effects of exercise on gut microbiota composition. Finally, we examine studies
      demonstrating the possible effects of mediators produced by gut microbiota on
      skeletal muscle, and intervention studies considering the effects of prebiotic or
      probiotic administration on muscle function. Even if there is no evidence of a
      distinct gut microbiota composition in older sarcopenic patients, we conclude
      that the literature supports the possible presence of a "gut-muscle axis",
      whereby gut microbiota may act as the mediator of the effects of nutrition on
      muscle cells.

PMID- 29189740
TI  - Aptamers and Glioblastoma: Their Potential Use for Imaging and Therapeutic
      Applications.
AB  - Glioblastoma is a highly aggressive primary brain tumour, renowned for its
      infiltrative growth and varied genetic profiles. The current treatment options
      are insufficient, and their off-target effects greatly reduce patient quality of
      life. The major challenge in improving glioblastoma diagnosis and treatment
      involves the development of a targeted imaging and drug delivery platform,
      capable of circumventing the blood brain barrier and specifically targeting
      glioblastoma tumours. The unique properties of aptamers demonstrate their
      capability of bridging the gap to the development of successful diagnosis and
      treatment options, where antibodies have previously failed. Aptamers possess many
      characteristics that make them an ideal novel imaging and therapeutic agent for
      the treatment of glioblastoma and other brain malignancies, and are likely to
      provide patients with a better standard of care and improved quality of life.
      Their target sensitivity, selective nature, ease of modification and low
      immunogenicity make them an ideal drug-delivery platform. This review article
      summarises the aptamers previously generated against glioblastoma cells or its
      identified biomarkers, and their potential application in diagnosis and
      therapeutic targeting of glioblastoma tumours.

PMID- 29189741
TI  - The Antitumor Constituents from Hedyotis Diffusa Willd.
AB  - As a TCM, Hedyotis diffusa Willd. has been using to treat malignant tumors, and
      many studies also showed that the extracts from Hedyotis diffusa Willd. possessed
      evident antitumor activities. Therefore, we carried out chemical study on
      Hedyotis diffusa Willd. and investigated the cytotoxicity of the obtained
      compounds on a panel of eight tumor cell lines. As a result, four new compounds
      were isolated from Hedyotis diffusa Willd., including three iridoid glycosides of
      Shecaoiridoidside A-C (1-3) and a cerebroside of shecaocerenoside A (4). Also,
      six known iridoid compounds (5-10) were also obtained. The cytotoxicity of all
      compounds against human tumor cell lines of HL-60, HeLa, HCT15, A459, HepG2, PC
      3, CNE-2, and BCG-823 were also evaluated in vitro. New compound 3 exhibited
      evident cytotoxicity to all tumor cell lines except the Hela, and the IC50 values
      are from 9.6 uM to 62.2 uM, while new compound 4 showed moderate cytotoxicity to
      all the cell lines, and the IC50 values are from 33.6 uM to 89.3 uM. By contrast,
      new compound 1 and known compound 9 showed moderate cytotoxicity to HCT15, A459,
      and HepG2 selectively. Known compound 7 also exhibited moderate cytotoxicity to
      HCT15 and A459 selectively.

PMID- 29189742
TI  - Targeting Metastasis with Snake Toxins: Molecular Mechanisms.
AB  - Metastasis involves the migration of cancer cells from a primary tumor to invade
      and establish secondary tumors in distant organs, and it is the main cause for
      cancer-related deaths. Currently, the conventional cytostatic drugs target the
      proliferation of malignant cells, being ineffective in metastatic disease. This
      highlights the need to find new anti-metastatic drugs. Toxins isolated from snake
      venoms are a natural source of potentially useful molecular scaffolds to obtain
      agents with anti-migratory and anti-invasive effects in cancer cells. While there
      is greater evidence concerning the mechanisms of cell death induction of several
      snake toxin classes on cancer cells; only a reduced number of toxin classes have
      been reported on (i.e., disintegrins/disintegrin-like proteins, C-type lectin
      like proteins, C-type lectins, serinproteases, cardiotoxins, snake venom
      cystatins) as inhibitors of adhesion, migration, and invasion of cancer cells.
      Here, we discuss the anti-metastatic mechanisms of snake toxins, distinguishing
      three targets, which involve (1) inhibition of extracellular matrix components
      dependent adhesion and migration, (2) inhibition of epithelial-mesenchymal
      transition, and (3) inhibition of migration by alterations in the
      actin/cytoskeleton network.

PMID- 29189743
TI  - Site I Inactivation Impacts Calmodulin Calcium Binding and Activation of
      Bordetella pertussis Adenylate Cyclase Toxin.
AB  - Site I inactivation of calmodulin (CaM) was used to examine the importance of
      aspartic acid 22 at position 3 in CaM calcium binding, protein folding, and
      activation of the Bordetella pertussis adenylate cyclase toxin domain (CyaA-ACD).
      NMR calcium titration experiments showed that site I in the CaM mutant (D22A)
      remained largely unperturbed, while sites II, III, and IV exhibited calcium
      induced conformational changes similar to wild-type CaM (CaMWt). Circular
      dichroism analyses revealed that D22A had comparable alpha-helical content to
      CaMWt, and only modest differences in alpha-helical composition were detected
      between CaMWt-CyaA-ACD and D22A-CyaA-ACD complexes. However, the thermal
      stability of the D22A-CyaA-ACD complex was reduced, as compared to the CaMWt-CyaA
      ACD complex. Moreover, CaM-dependent activity of CyaA-ACD decreased 87% in the
      presence of D22A. Taken together, our findings provide evidence that D22A engages
      CyaA-ACD, likely through C-terminal mediated binding, and that site I
      inactivation exerts functional effects through the modification of stabilizing
      interactions that occur between N-terminal CaM and CyaA-ACD.

PMID- 29189745
TI  - Properties of Concrete Paving Blocks and Hollow Tiles with Recycled Aggregate
      from Construction and Demolition Wastes.
AB  - In recent years there has been an increasing tendency to recycle the wastes
      generated by building companies in the construction industry, demolition wastes
      being the most important in terms of volume. The aim of this work is to study the
      possibility of using recycled aggregates from construction and demolition wastes
      in the preparation of precast non-structural concretes. To that purpose, two
      different percentages (15% and 30%) of natural aggregates were substituted by
      recycled aggregates in the manufacture of paving blocks and hollow tiles. Dosages
      used by the company have not been changed by the introduction of recycled
      aggregate. Precast elements have been tested by means of compressive and flexural
      strength, water absorption, density, abrasion, and slipping resistance. The
      results obtained show the possibility of using these wastes at an industrial
      scale, satisfying the requirements of the Spanish standards for these elements.

PMID- 29189744
TI  - Nanoparticle/Metal-Organic Framework Composites for Catalytic Applications:
      Current Status and Perspective.
AB  - Nanoparticle/metal-organic frameworks (MOF) based composites have recently
      attracted significant attention as a new class of catalysts. Such composites
      possess the unique features of MOFs (including clearly defined crystal structure,
      high surface area, single site catalyst, special confined nanopore, tunable, and
      uniform pore structure), but avoid some intrinsic weaknesses (like limited
      electrical conductivity and lack in the "conventional" catalytically active
      sites). This review summarizes the developed strategies for the fabrication of
      nanoparticle/MOF composites for catalyst uses, including the strategy using MOFs
      as host materials to hold and stabilize the guest nanoparticles, the strategy
      with subsequent MOF growth/assembly around pre-synthesized nanoparticles and the
      strategy mixing the precursors of NPs and MOFs together, followed by self
      assembly process or post-treatment or post-modification. The applications of
      nanoparticle/MOF composites for CO oxidation, CO2 conversion, hydrogen
      production, organic transformations, and degradation of pollutants have been
      discussed. Superior catalytic performances in these reactions have been
      demonstrated. Challenges and future developments are finally addressed.

PMID- 29189746
TI  - Blue and Red LED Illumination Improves Growth and Bioactive Compounds Contents in
      Acyanic and Cyanic Ocimum basilicum L. Microgreens.
AB  - Microgreens are an excellent source of health-maintaining compounds, and the
      accumulation of these compounds in plant tissues may be stimulated by exogenous
      stimuli. While light quality effects on green basil microgreens are known, the
      present paper aims at improving the quality of acyanic (green) and cyanic (red)
      basil microgreens with different ratios of LED blue and red illumination. Growth,
      assimilatory and anthocyanin pigments, chlorophyll fluorescence, total phenolic,
      flavonoids, selected phenolic acid contents and antioxidant activity were
      assessed in microgreens grown for 17 days. Growth of microgreens was enhanced
      with predominantly blue illumination, larger cotyledon area and higher fresh
      mass. The same treatment elevated chlorophyll a and anthocyanin pigments
      contents. Colored light treatments decreased chlorophyll fluorescence PhiPSII
      values significantly in the green cultivar. Stimulation of phenolic synthesis and
      free radical scavenging activity were improved by predominantly red light in the
      green cultivar (up to 1.87 fold) and by predominantly blue light in the red
      cultivar (up to 1.73 fold). Rosmarinic and gallic acid synthesis was higher (up
      to 15- and 4-fold, respectively, compared to white treatment) in predominantly
      blue illumination. Red and blue LED ratios can be tailored to induce superior
      growth and phenolic contents in both red and green basil microgreens, as a
      convenient tool for producing higher quality foods.

PMID- 29189747
TI  - Neurological and Sleep Disturbances in Bronchiectasis.
AB  - Bronchiectasis unrelated to cystic fibrosis is a chronic lung disease that is
      increasingly recognised worldwide. While other common chronic lung conditions
      such as chronic obstructive lung disease have been associated with cardiovascular
      disease, there is a paucity of data on the relationship between bronchiectasis
      and cardiovascular risks such as stroke and sleep disturbance. Furthermore, it is
      unclear whether other neuropsychological aspects are affected, such as cognition,
      cerebral infection, anxiety and depression. In this review, we aim to highlight
      neurological and sleep issues in relation to bronchiectasis and their importance
      to patient care.

PMID- 29189748
TI  - Physiology of the Inactivation of Vegetative Bacteria by Thermal Treatments: Mode
      of Action, Influence of Environmental Factors and Inactivation Kinetics.
AB  - Heat has been used extensively in the food industry as a preservation method,
      especially due to its ability to inactivate microorganisms present in foods.
      However, many aspects regarding the mechanisms of bacterial inactivation by heat
      and the factors affecting this process are still not fully understood. The
      purpose of this review is to offer a general overview of the most important
      aspects of the physiology of the inactivation or survival of microorganisms,
      particularly vegetative bacteria, submitted to heat treatments. This could help
      improve the design of current heat processes methods in order to apply milder
      and/or more effective treatments that could fulfill consumer requirements for
      fresh-like foods while maintaining the advantages of traditional heat treatments.

PMID- 29189749
TI  - Effect of Low Temperature Cultivation on the Phytochemical Profile and
      Bioactivity of Arctic Plants: A Case of Dracocephalum palmatum.
AB  - The influence of climatic factors, e.g., low temperature, on the phytochemical
      composition and bioactivity of the arctic plant Dracocephalum palmatum Steph. ax
      Willd. (palmate dragonhead), a traditional food and medical herb of Northern
      Siberia, was investigated. D. palmatum seedlings were grown in a greenhouse
      experiment at normal (20  degrees C, NT) and low (1  degrees C, LT) temperature
      levels and five groups of components that were lipophilic and hydrophilic in
      nature were characterized. The analyses indicated that D. palmatum under NT
      demonstrates high content of photosynthetic pigments, specific fatty acid (FA)
      profile with domination of saturated FA (53.3%) and the essential oil with trans
      pinocamphone as a main component (37.9%). Phenolic compounds were identified
      using a combination of high performance liquid chromatography with diode array
      detection and electrospray ionization mass-spectrometric detection (HPLC-DAD-ESI
      MS) techniques, as well as free carbohydrates and water soluble polysaccharides.
      For the first time, it was established that the cold acclimation of D. palmatum
      seedlings resulted in various changes in physiological and biochemical parameters
      such as membrane permeability, photosynthetic potential, membrane fluidity, leaf
      surface secretory function, reactive oxygen species-antioxidant balance,
      osmoregulator content and cell wall polymers. In brief, results showed that the
      adaptive strategy of D. palmatum under LT was realized on the accumulation of
      membrane or surface components with more fluid properties (unsaturated FA and
      essential oils), antioxidants (phenolic compounds and enzymes), osmoprotectants
      (free sugars) and cell wall components (polysaccharides). In addition, the
      occurrence of unusual flavonoids including two new isomeric malonyl esters of
      eriodictyol-7-O-glucoside was found in LT samples. Data thus obtained allow
      improving our understanding of ecophysiological mechanisms of cold adaptation of
      arctic plants.

PMID- 29189750
TI  - Multi-Source Generation Mechanisms for Low Frequency Noise Induced by Flood
      Discharge and Energy Dissipation from a High Dam with a Ski-Jump Type Spillway.
AB  - As excess water is discharged from a high dam, low frequency noise (air pulsation
      lower than 10 Hz, LFN) is generated and propagated in the surrounding areas,
      causing environmental hazards such as the vibration of windows and doors and the
      discomfort of local residents. To study the generation mechanisms and key
      influencing factors of LFN induced by flood discharge and energy dissipation from
      a high dam with a ski-jump type spillway, detailed prototype observations and
      analyses of LFN are carried out. The discharge flow field is simulated and
      analyzed using a gas-liquid turbulent flow model. The acoustic response
      characteristics of the air cavity, which is formed between the discharge nappe
      and dam body, are analyzed using an acoustic numerical model. The multi-sources
      generation mechanisms are first proposed basing on the prototype observation
      results, vortex sound model, turbulent flow model and acoustic numerical model.
      Two kinds of sources of LFN are studied. One comes from the energy dissipation of
      submerged jets in the plunge pool, the other comes from nappe-cavity coupled
      vibration. The results of the analyses reveal that the submerged jets in the
      plunge pool only contribute to an on-site LFN energy of 0-1.0 Hz, and the strong
      shear layers around the high-velocity submerged jets and wall jet development
      areas are the main acoustic source regions of LFN in the plunge pool. In
      addition, the nappe-cavity coupled vibration, which is induced when the discharge
      nappe vibrates with close frequency to the model frequency of the cavity, can
      induce on-site LFN energy with wider frequency spectrum energy within 0-4.0 Hz.
      By contrast, the contribution degrees to LFN energy from two acoustic sources are
      almost same, while the contribution degree from nappe-cavity coupled vibration is
      slightly higher.

PMID- 29189751
TI  - Partial and Total Annoyance Due to Road Traffic Noise Combined with Aircraft or
      Railway Noise: Structural Equation Analysis.
AB  - Structural equation modeling was used to analyze partial and total in situ
      annoyance in combined transportation noise situations. A psychophysical total
      annoyance model and a perceptual total annoyance model were proposed. Results
      show a high contribution of Noise exposure and Noise sensitivity to Noise
      annoyance, as well as a causal relationship between noise annoyance and lower
      Dwelling satisfaction. Moreover, the Visibility of noise source may increase
      noise annoyance, even when the visible noise source is different from the
      annoying source under study. With regards to total annoyance due to road traffic
      noise combined with railway or aircraft noise, even though in both situations
      road traffic noise may be considered background noise and the other noise source
      event noise, the contribution of road traffic noise to the models is greater than
      railway noise and smaller than aircraft noise. This finding may be explained by
      the difference in sound pressure levels between these two types of combined
      exposures or by the aircraft noise level, which may also indicate the city in
      which the respondents live. Finally, the results highlight the importance of
      sample size and variable distribution in the database, as different results can
      be observed depending on the sample or variables considered.

PMID- 29189752
TI  - T-2 Toxin/HT-2 Toxin and Ochratoxin A ELISAs Development and In-House Validation
      in Food in Accordance with the Commission Regulation (EU) No 519/2014.
AB  - T-2 toxin/HT-2 toxin (T-2/HT-2) and ochratoxin A (OTA) are mycotoxins that can
      contaminate a variety of agricultural commodities. To protect consumers' health,
      indicative limits for T-2/HT-2 and maximum limits for OTA have been set by the
      European Commission, requiring food business operators and controlling agencies
      to conduct routine checks for the presence of these harmful contaminants.
      Screening methods are increasingly used for monitoring purposes. Due to the
      demand for new and improved screening tools, two individual detection methods, T
      2/HT-2 and OTA enzyme-linked immunosorbent assays (ELISAs), were developed in
      this study. The T-2/HT-2 ELISA was based on a T-2 monoclonal antibody with an
      IC50 (50% inhibitory concentration) of 0.28 ng/mL and 125% cross-reactivity with
      HT-2. As regards the OTA ELISA, a new sensitive monoclonal antibody specific to
      OTA with an IC50 of 0.13 ng/mL was produced. Both developed ELISA tests were then
      validated in agricultural commodities in accordance with the new performance
      criteria guidelines for the validation of screening methods for mycotoxins
      included in Commission Regulation (EU) No 519/2014. The T-2/HT-2 ELISA was
      demonstrated to be suitable for the detection of T-2/HT-2 in cereals and baby
      food at and above the screening target concentration (STC) of 12.5 MUg/kg and 7.5
      MUg/kg, respectively. The OTA ELISA was shown to be applicable for the detection
      of OTA in cereals, coffee, cocoa and wine at and above the STC of 2 MUg/kg, 2.5
      MUg/kg, 2.5 MUg/kg and 0.4 ng/mL, respectively. The accuracy of both ELISAs was
      further confirmed by analysing proficiency test and reference samples. The
      developed methods can be used for sensitive and high-throughput screening for the
      presence of T-2/HT-2 and OTA in agricultural commodities.

PMID- 29189753
TI  - A Sensitive and Stable Surface Plasmon Resonance Sensor Based on Monolayer
      Protected Silver Film.
AB  - In this paper, we present a stable silver-based surface plasmon resonance (SPR)
      sensor using a self-assembled monolayer (SAM) as a protection layer and
      investigated its efficiency in water and 0.01 M phosphate buffered saline (PBS).
      By simulation, silver-based SPR sensor has a better performance in field
      enhancement and penetration depth than that of a gold-based SPR sensor, which are
      5 and 1.4 times, respectively. To overcome the instability of the bare silver
      film and investigate the efficiency of the protected layer, the SAM of 11
      mercapto-1-undecanol (MUD) was used as a protection layer. Stability experiment
      results show that the protected silver film exhibited excellent stability either
      in pure water or 0.01 M PBS buffer. The sensitivity of the silver-based SPR
      sensor was calculated to be 127.26 deg/RIU (refractive index unit), measured with
      different concentrations of NaCl solutions. Further, a very high refractive
      resolution for the silver-based SPR sensor was found to be 2.207 * 10-7 RIU,
      which reaches the theoretical limit in the wavelength of 632.8 nm for a SPR
      sensor reported in the literature. Using a mixed SAM of 16-mercaptohexadecanoic
      acid (MHDA) and a MUD layer with a ratio of 1:10, this immunosensor for the
      rabbit immunoglobulin G (IgG) molecule with a limit of detection as low as 22.516
      ng/mL was achieved.

PMID- 29189755
TI  - Study of Optical Fiber Sensors for Cryogenic Temperature Measurements.
AB  - In this work, the performance of five different fiber optic sensors at cryogenic
      temperatures has been analyzed. A photonic crystal fiber Fabry-Perot
      interferometer, two Sagnac interferometers, a commercial fiber Bragg grating
      (FBG), and a pi-phase shifted fiber Bragg grating interrogated in a random
      distributed feedback fiber laser have been studied. Their sensitivities and
      resolutions as sensors for cryogenic temperatures have been compared regarding
      their advantages and disadvantages. Additionally, the results have been compared
      with the given by a commercial optical backscatter reflectometer that allowed for
      distributed temperature measurements of a single mode fiber.

PMID- 29189754
TI  - Microbial Insight into a Pilot-Scale Enhanced Two-Stage High-Solid Anaerobic
      Digestion System Treating Waste Activated Sludge.
AB  - High solid anaerobic digestion (HSAD) is a rapidly developed anaerobic digestion
      technique for treating municipal sludge, and has been widely used in Europe and
      Asia. Recently, the enhanced HSAD process with thermal treatment showed its
      advantages in both methane production and VS reduction. However, the
      understanding of the microbial community is still poor. This study investigated
      microbial communities in a pilot enhanced two-stage HSAD system that degraded
      waste activated sludge at 9% solid content. The system employed process "thermal
      pre-treatment (TPT) at 70  degrees C, thermophilic anaerobic digestion (TAD), and
      mesophilic anaerobic digestion (MAD)". Hydrogenotrophic methanogens
      Methanothermobacter spp. dominated the system with relative abundance up to about
      100% in both TAD and MAD. Syntrophic acetate oxidation (SAO) bacteria were
      discovered in TAD, and they converted acetate into H2 and CO2 to support
      hydrogenotrophic methanogenesis. The microbial composition and conversion route
      of this system are derived from the high solid content and protein content in raw
      sludge, as well as the operational conditions. This study could facilitate the
      understanding of the enhanced HSAD process, and is of academic and industrial
      importance.

PMID- 29189756
TI  - The Role of China in the UK Relative Imports from Three Selected Trading Regions:
      The Case of Textile Raw Material Industry.
AB  - The UK textile industry was very prosperous in the past but in the 1970s Britain
      started to import textile materials from abroad. Since 1990, half of its textile
      materials have been imported from the EEA (European Economic Area), ASEAN
      (Association of Southeast Asian Nations) and North America countries. Meanwhile,
      UK imports from China have increased dramatically. Through comparisons, this
      paper calculates the trade competitiveness index and relative competitive
      advantages of regions and investigates the impact of Chinese textiles on UK
      imports from three key free trade regions across the textile sectors in the
      period 1990-2016 on the basis of United Nation Comtrade Rev. 3. We find that
      China's textile prices, product techniques, political trade barriers and even tax
      system have made a varied impact on the UK's imports across related sectors in
      the context of green trade and the strengthening of barriers, which helps us
      recognize China's competitiveness in international trading and also provides
      advice on China's sustainable development of textile exports.

PMID- 29189757
TI  - A Denoising Method for Randomly Clustered Noise in ICCD Sensing Images Based on
      Hypergraph Cut and Down Sampling.
AB  - Intensified charge-coupled device (ICCD) images are captured by ICCD sensors in
      extremely low-light conditions. They often contains spatially clustered noises
      and general filtering methods do not work well. We find that the scale of the
      clustered noise in ICCD sensing images is often much smaller than that of the
      true structural information. Then the clustered noise can be identified by
      properly down-sampling and then up-sampling the ICCD sensing image and comparing
      it to the noisy image. Based on this finding, we present a denoising algorithm to
      remove the randomly clustered noise in ICCD images. First, we over-segment the
      ICCD image into a set of flat patches, and each patch contains very little
      structural information. Second, we classify the patches into noisy patches and
      noise-free patches based on the hypergraph cut method. Then the noise-free
      patches are easily recovered by the general block-matching and 3D filtering
      (BM3D) algorithm, since they often do not contain the clustered noise. The noisy
      patches are recovered by subtracting the identified clustered noise from the
      noisy patches. After that, we could get the whole recovered ICCD image. Finally,
      the quality of the recovered ICCD image is further improved by diminishing the
      remaining sparse noise with robust principal component analysis. Experiments are
      conducted on a set of ICCD images and compared with four existing denoising
      algorithms, which shows that the proposed algorithm removes well the randomly
      clustered noise and preserves the true textural information in the ICCD sensing
      images.

PMID- 29189758
TI  - Modeling of Sensor Placement Strategy for Shape Sensing and Structural Health
      Monitoring of a Wing-Shaped Sandwich Panel Using Inverse Finite Element Method.
AB  - This paper investigated the effect of sensor density and alignment for three
      dimensional shape sensing of an airplane-wing-shaped thick panel subjected to
      three different loading conditions, i.e., bending, torsion, and membrane loads.
      For shape sensing analysis of the panel, the Inverse Finite Element Method (iFEM)
      was used together with the Refined Zigzag Theory (RZT), in order to enable
      accurate predictions for transverse deflection and through-the-thickness
      variation of interfacial displacements. In this study, the iFEM-RZT algorithm is
      implemented by utilizing a novel three-node C degrees -continuous inverse-shell
      element, known as i3-RZT. The discrete strain data is generated numerically
      through performing a high-fidelity finite element analysis on the wing-shaped
      panel. This numerical strain data represents experimental strain readings
      obtained from surface patched strain gauges or embedded fiber Bragg grating (FBG)
      sensors. Three different sensor placement configurations with varying density and
      alignment of strain data were examined and their corresponding displacement
      contours were compared with those of reference solutions. The results indicate
      that a sparse distribution of FBG sensors (uniaxial strain measurements), aligned
      in only the longitudinal direction, is sufficient for predicting accurate full
      field membrane and bending responses (deformed shapes) of the panel, including a
      true zigzag representation of interfacial displacements. On the other hand, a
      sparse deployment of strain rosettes (triaxial strain measurements) is
      essentially enough to produce torsion shapes that are as accurate as those of
      predicted by a dense sensor placement configuration. Hence, the potential
      applicability and practical aspects of i3-RZT/iFEM methodology is proven for
      three-dimensional shape-sensing of future aerospace structures.

PMID- 29189759
TI  - Study of SH-SY5Y Cancer Cell Response to Treatment with Polyphenol Extracts Using
      FT-IR Spectroscopy.
AB  - Plant polyphenols are important components of human diet and a number of them are
      considered to possess chemo-preventive and therapeutic properties against cancer.
      They are recognized as naturally occurring antioxidants, but also as pro-oxidant,
      pro-apoptotic, or chromosomal aberrations inducers, depending on their
      concentration and/or the stage of cell-cycle of the cells with which they
      interact. For these reasons, particular interest is devoted to knowing the total
      effects of polyphenols on the cell cycle and metabolism. Fourier-Transform
      Infrared (FT-IR) spectroscopy thanks to its ability in analyzing cells at a
      molecular level can be particularly useful in investigating the biochemical
      changes induced in protein, nucleic acid, lipid, and carbohydrate content of
      cells by means of polyphenols administration. Spectroscopic analysis was
      performed on in vitro human SH-SY5Y neuroblastoma cells that were exposed to
      different doses of a cherry derived polyphenol extract. The infrared spectra that
      were obtained from unexposed and exposed cells show significant differences that
      can be helpful in order to understand the cells-polyphenols interaction.

PMID- 29189760
TI  - Electrochemical Immunosensor for the Detection of Aflatoxin B1 in Palm Kernel
      Cake and Feed Samples.
AB  - Palm kernel cake (PKC) is the solid residue following oil extraction of palm
      kernels and useful to fatten animals either as a single feed with only minerals
      and vitamins supplementation, or mixed with other feedstuffs such as corn kernels
      or soy beans. The occurrence of mycotoxins (aflatoxins, ochratoxins, zearalenone,
      and fumonisins) in feed samples affects the animal's health and also serves as a
      secondary contamination to humans via consumption of eggs, milk and meats. Of
      these, aflatoxin B1 (AFB1) is the most toxically potent and a confirmed
      carcinogen to both humans and animals. Methods such as High Performance Liquid
      Chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LC-MS/MS) are
      common in the determination of mycotoxins. However, these methods usually require
      sample pre-treatment, extensive cleanup and skilled operator. Therefore, in the
      present work, a rapid method of electrochemical immunosensor for the detection of
      AFB1 was developed based on an indirect competitive enzyme-linked immunosorbent
      assay (ELISA). Multi-walled carbon nanotubes (MWCNT) and chitosan (CS) were used
      as the electrode modifier for signal enhancement. N-ethyl-N'-(3
      dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) activated
      the carboxyl groups at the surface of nanocomposite for the attachment of AFB1
      BSA antigen by covalent bonding. An indirect competitive reaction occurred
      between AFB1-BSA and free AFB1 for the binding site of a fixed amount of anti
      AFB1 antibody. A catalytic signal based on horseradish peroxidase (HRP) in the
      presence of hydrogen peroxide (H2O2) and 3,3',5,5'-tetramethylbenzidine (TMB)
      mediator was observed as a result of attachment of the secondary antibody to the
      immunoassay system. As a result, the reduction peak of TMB(Ox) was measured by
      using differential pulse voltammetry (DPV) analysis. Based on the results, the
      electrochemical surface area was increased from 0.396 cm2 to 1.298 cm2 due to the
      electrode modification with MWCNT/CS. At the optimal conditions, the working
      range of the electrochemical immunosensor was from 0.0001 to 10 ng/mL with limit
      of detection of 0.1 pg/mL. Good recoveries were obtained for the detection of
      spiked feed samples (PKC, corn kernels, soy beans). The developed method could be
      used for the screening of AFB1 in real samples.

PMID- 29189761
TI  - Heterogenization of Ketone Catalyst for Epoxidation by Low Pressure Plasma
      Fluorination of Silica Gel Supports.
AB  - Low pressure plasma was used for preparing heterogeneous organocatalysts 2-(A)
      (C) suitable for dioxirane-mediated epoxidations. Heterogenization was
      accomplished by adsorption of the methyl perfluoroheptyl ketone (2) on
      fluorinated supports (A)-(C) deriving from the treatment of commercial C8-silica
      gel in low pressure plasma fed with fluorocarbons. Catalyst 2-(C) proved to be
      the most efficient one, promoting epoxidation of an array of alkenes, including
      unsaturated fatty esters like methyl oleate (10) and the triglyceride soybean oil
      (11), with the cheap potassium peroxymonosulfate KHSO5 (caroate) as a green
      oxidant. Notably, the perfluorinated matrix gives rise to the activation of
      caroate, generating singlet oxygen. Materials were characterized by infrared
      Attenuated Total Reflectance spectroscopy (ATR-FTIR), X-ray Photoelectron
      Spectroscopy (XPS ) and Emission Scanning Electron Microscope (FESEM).

PMID- 29189763
TI  - Formation and Stability of Prebiotically Relevant Vesicular Systems in
      Terrestrial Geothermal Environments.
AB  - Terrestrial geothermal fields and oceanic hydrothermal vents are considered as
      candidate environments for the emergence of life on Earth. Nevertheless, the
      ionic strength and salinity of oceans present serious limitations for the self
      assembly of amphiphiles, a process that is fundamental for the formation of first
      protocells. Consequently, we systematically characterized the efficiency of
      amphiphile assembly, and vesicular stability, in terrestrial geothermal
      environments, both, under simulated laboratory conditions and in hot spring water
      samples (collected from Ladakh, India, an Astrobiologically relevant site).
      Combinations of prebiotically pertinent fatty acids and their derivatives were
      evaluated for the formation of vesicles in aforesaid scenarios. Additionally, the
      stability of these vesicles was characterized over multiple dehydration
      rehydration cycles, at elevated temperatures. Among the combinations that were
      tested, mixtures of fatty acid and its glycerol derivatives were found to be the
      most robust, also resulting in vesicles in all of the hot spring waters that were
      tested. Importantly, these vesicles were stable at high temperatures, and this
      fatty acid system retained its vesicle forming propensity, even after multiple
      cycles of dehydration-rehydration. The remaining systems, however, formed
      vesicles only in bicine buffer. Our results suggest that certain prebiotic
      compartments would have had a selective advantage in terrestrial geothermal
      niches. Significantly, our study highlights the importance of validating results
      that are obtained under 'buffered' laboratory conditions, by verifying their
      plausibility in prebiotically analogous environments.

PMID- 29189762
TI  - Synthesis and In Vitro Antimycobacterial Activity of Novel N-Arylpiperazines
      Containing an Ethane-1,2-diyl Connecting Chain.
AB  - Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2
      fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; 8a-h) have
      been designed and synthesized through multistep reactions as a part of on-going
      research programme focused on finding new antimycobacterials. Lipophilic
      properties of these compounds were estimated by RP-HPLC using methanol/water
      mobile phases with a various volume fraction of the organic modifier. The log kw
      values, which were extrapolated from intercepts of a linear relationship between
      the logarithm of a retention factor k (log k) and volume fraction of a mobile
      phase modifier (phiM), varied from 2.113 (compound 8e) to 2.930 (compound 8h) and
      indicated relatively high lipophilicity of these salts. Electronic properties of
      the molecules 8a-h were investigated by evaluation of their UV/Vis spectra. In a
      next phase of the research, the compounds 8a-h were in vitro screened against M.
      tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794), M. kansasii
      CNCTC My 235/80 (identical with ATCC 12478), a M. kansasii 6 509/96 clinical
      isolate, M. avium CNCTC My 330/80 (identical with ATCC 25291) and M. avium
      intracellulare ATCC 13950, respectively, as well as against M. kansasii CIT11/06,
      M. avium subsp. paratuberculosis CIT03 and M. avium hominissuis CIT10/08 clinical
      isolates using isoniazid, ethambutol, ofloxacin, ciprofloxacin or pyrazinamide as
      reference drugs. The tested compounds 8a-h were found to be the most promising
      against M. tuberculosis; a MIC = 8 MUM was observed for the most effective 1-(2
      {4-[(butoxycarbonyl)amino]phen-ylphenyl}-2-hydroxyethyl)-4-(2
      fluorophenyl)piperazin-1-ium chloride (8h). In addition, all of them showed low
      (insignificant) in vitro toxicity against a human monocytic leukemia THP-1 cell
      line, as observed LD50 values > 30 MUM indicated. The structure-antimycobacterial
      activity relationships of the analyzed 8a-h series are also discussed.

PMID- 29189764
TI  - A Comprehensive Approach to Motorcycle-Related Head Injury Prevention:
      Experiences from the Field in Vietnam, Cambodia, and Uganda.
AB  - Motorcyclists account for 23% of global road traffic deaths and over half of
      fatalities in countries where motorcycles are the dominant means of transport.
      Wearing a helmet can reduce the risk of head injury by as much as 69% and death
      by 42%; however, both child and adult helmet use are low in many countries where
      motorcycles are a primary mode of transportation. In response to the need to
      increase helmet use by all drivers and their passengers, the Global Helmet
      Vaccine Initiative (GHVI) was established to increase helmet use in three
      countries where a substantial portion of road users are motorcyclists and where
      helmet use is low. The GHVI approach includes five strategies to increase helmet
      use: targeted programs, helmet access, public awareness, institutional policies,
      and monitoring and evaluation. The application of GHVI to Vietnam, Cambodia, and
      Uganda resulted in four key lessons learned. First, motorcyclists are more likely
      to wear helmets when helmet use is mandated and enforced. Second, programs
      targeted to at-risk motorcyclists, such as child passengers, combined with
      improved awareness among the broader population, can result in greater public
      support needed to encourage action by decision-makers. Third, for broad
      population-level change, using multiple strategies in tandem can be more
      effective than using a single strategy alone. Lastly, the successful expansion of
      GHVI into Cambodia and Uganda has been hindered by the lack of helmet
      accessibility and affordability, a core component contributing to its success in
      Vietnam. This paper will review the development of the GHVI five-pillar approach
      in Vietnam, subsequent efforts to implement the model in Cambodia and Uganda, and
      lessons learned from these applications to protect motorcycle drivers and their
      adult and child passengers from injury.

PMID- 29189765
TI  - Phylogenetic Analysis of the SNORD116 Locus.
AB  - The SNORD116 small nucleolar RNA locus (SNORD116@) is contained within the long
      noncoding RNA host gene SNHG14 on human chromosome 15q11-q13. The SNORD116 locus
      is a cluster of 28 or more small nucleolar (sno) RNAs; C/D box (SNORDs).
      Individual RNAs within the cluster are tandem, highly similar sequences, referred
      to as SNORD116-1, SNORD116-2, etc., with the entire set referred to as SNORD116@.
      There are also related SNORD116 loci on other chromosomes, and these additional
      loci are conserved among primates. Inherited chromosomal 15q11-q13 deletions,
      encompassing the SNORD116@ locus, are causative for the paternally
      inherited/maternally-imprinted genetic condition, Prader-Willi syndrome (PWS).
      Using in silico tools, along with molecular-based and sequenced-based
      confirmation, phylogenetic analysis of the SNORD116@ locus was performed. The
      consensus sequence for the SNORD116@ snoRNAs from various species was determined
      both for all the SNORD116 snoRNAs, as well as those grouped using sequence and
      location according to a human grouping convention. The implications of these
      findings are put in perspective for studying SNORD116 in patients with inherited
      Prader-Willi syndrome, as well as model organisms.

PMID- 29189766
TI  - Health Challenges in Refugee Reception: Dateline Europe 2016.
AB  - The arrival of more than one million migrants, many of them refugees, has proved
      a major test for the European Union. Although international relief and monitoring
      agencies have been critical of makeshift camps in Calais and Eidomeni where
      infectious disease and overcrowding present major health risks, few have examined
      the nature of the official reception system and its impact on health delivery.
      Drawing upon research findings from an Economic and Social Research Council
      (ESRC) funded project, this article considers the physical and mental health of
      asylum-seekers in transit and analyses how the closure of borders has engendered
      health risks for populations in recognised reception centres in Sicily and in
      Greece. Data gathered by means of a survey administered in Greece (300) and in
      Sicily (400), and complemented by in-depth interviews with migrants (45) and key
      informants (50) including representatives of government offices, humanitarian and
      relief agencies, NGOs and activist organisations, are presented to offer an
      analysis of the reception systems in the two frontline states. We note that
      medical provision varies significantly from one centre to another and that centre
      managers play a critical role in the transmission of vital information. A key
      finding is that, given such disparity, the criteria used by the UNHCR to grade
      health services reception do not address the substantive issue that prevent
      refugees from accessing health services, even when provided on site. Health
      provision is not as recorded in UNHCR reporting but rather there are critical
      gaps between provision, awareness, and access for refugees in reception systems
      in Sicily and in Greece. This article concludes that there is a great need for
      more information campaigns to direct refugees to essential services.

PMID- 29189767
TI  - Blood-Based Protein Signatures for Early Detection of Colorectal Cancer: A
      Systematic Review.
AB  - OBJECTIVES: Blood-based proteins might be an attractive option for early
      detection of colorectal cancer (CRC), but individually they are unlikely to
      achieve the diagnostic performance required for population based screening. We
      aimed at summarizing current evidence of diagnostic performance of signatures
      based on multiple proteins for early detection of CRC. METHODS: A systematic
      literature review adhering to the PRISMA (preferred reporting items for
      systematic reviews and meta-analysis) guidelines was performed. PubMed and Web of
      Science databases were searched for potentially relevant studies published until
      28th August, 2017. Relevant studies were identified by predefined eligibility
      criteria. Estimates of indicators of diagnostic performance such as sensitivity,
      specificity, and the area under the curve (AUC), along with information on
      validation and other key methodological procedures were extracted. Study quality
      was assessed by a QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2)
      instrument tool. RESULTS: Thirty six eligible studies with numbers of CRC cases
      ranging from 23 to 512 and the number of proteins included in signatures ranged
      from 3 to 13 were identified. Reported Youden's Index and AUC ranged from 0.19 to
      0.95 and from 0.62 to 0.996, respectively. However most studies, especially those
      reporting better diagnostic performance, were conducted in clinical rather than
      screening setting and many studies lacked any internal or external validation of
      identified algorithm. CONCLUSIONS: Blood-based tests using signatures of multiple
      proteins may be a promising approach for non-invasive CRC screening. However,
      promising signatures identified in clinical settings still require rigorous
      evaluation in large studies conducted in true screening setting.

PMID- 29189768
TI  - Inflammatory Bowel Disease Adversely Impacts Colorectal Cancer Surgery Short-term
      Outcomes and Health-Care Resource Utilization.
AB  - OBJECTIVES: Inflammatory bowel disease (IBD) is associated with an increased risk
      of colorectal cancer (CRC) compared to patients without IBD. There is a lack of
      population-based data evaluating the in-patient surgical outcomes of CRC in IBD
      patients. We sought to compare the hospital outcomes of CRC surgery between
      patients with and without IBD. METHODS: We used the National Inpatient Sample
      (2008-2012) and Nationwide Readmissions Database (NRD, 2013) and selected all
      adult patients (age >=18 years) with ulcerative colitis (UC) or Crohn's disease
      (CD) who underwent CRC surgery. Multivariate analysis for in-patient outcomes of
      postoperative complications, health-care resource utilization, readmission rate,
      and mortality were performed. RESULTS: A total of 397,847 patients underwent CRC
      surgery from 2008 to 2012, of which 0.8% (3,242) had IBD. Compared to CRC in non
      IBD patients, CRC in IBD patients had longer length of stay (adjusted coefficient
      (AC) 0.86 days, 95% confidence interval (CI): 0.42, 1.30), more likely developed
      postoperative complications (adjusted odds ratio (AOR) 1.26, 95% CI: 1.06, 1.50),
      including postoperative infection (AOR 1.69, 95% CI: 1.20, 2.38) and deep vein
      thrombosis (AOR 2.42, 95% CI: 1.36, 4.28), and more frequently required blood
      transfusion (AOR 1.59, 95% CI: 1.30, 1.94). CRC in IBD patients was more likely
      to be readmitted within 30 days (AOR 1.44, 95% CI: 1.01, 2.04). CONCLUSION: At a
      population level, IBD adversely impacts outcomes at the time of CRC surgery.

PMID- 29189769
TI  - Preparation of viable adult ventricular myocardial slices from large and small
      mammals.
AB  - This protocol describes the preparation of highly viable adult ventricular
      myocardial slices from the hearts of small and large mammals, including rodents,
      pigs, dogs and humans. Adult ventricular myocardial slices are 100- to 400-MUm
      thick slices of living myocardium that retain the native multicellularity,
      architecture and physiology of the heart. This protocol provides a list of the
      equipment and reagents required alongside a detailed description of the
      methodology for heart explantation, tissue preparation, slicing with a vibratome
      and handling of myocardial slices. Supplementary videos are included to visually
      demonstrate these steps. A number of critical steps are addressed that must be
      followed in order to prepare highly viable myocardial slices. These include
      identification of myocardial fiber direction and fiber alignment within the
      tissue block, careful temperature control, use of an excitation-contraction
      uncoupler, optimal vibratome settings and correct handling of myocardial slices.
      Many aspects of cardiac structure and function can be studied using myocardial
      slices in vitro. Typical results obtained with hearts from a small mammal (rat)
      and a large mammal (human) with heart failure are shown, demonstrating myocardial
      slice viability, maximum contractility, Ca2+ handling and structure. This
      protocol can be completed in ~4 h.

PMID- 29189770
TI  - Langmuir-Blodgett nanotemplates for protein crystallography.
AB  - The new generation of synchrotrons and microfocused beamlines has enabled great
      progress in X-ray protein crystallography, resulting in new 3D atomic structures
      for proteins of high interest to the pharmaceutical industry and life sciences.
      It is, however, often still challenging to produce protein crystals of sufficient
      size and quality (order, intensity of diffraction, radiation stability). In this
      protocol, we provide instructions for performing the Langmuir-Blodgett (LB)
      nanotemplate method, a crystallization approach that can be used for any protein
      (including membrane proteins). We describe how to produce highly ordered 2D LB
      protein monolayers at the air-water interface and deposit them on glass slides.
      LB-film formation can be observed by surface-pressure measurements and Brewster
      angle microscopy (BAM), although its quality can be characterized by atomic force
      microscopy (AFM) and nanogravimetry. Such films are then used as a 2D template
      for triggering 3D protein crystal formation by hanging-drop vapor diffusion. The
      procedure for forming the 2D template takes a few minutes. Structural information
      about the protein reorganization in the LB film during the crystallization
      process on the nano level can be obtained using an in situ submicron GISAXS
      (grazing-incidence small-angle X-ray scattering) method. MicroGISAXS spectra,
      measured directly at the interface of the LB films and protein solution in real
      time, as described in this protocol, can be interpreted in terms of the buildup
      of layers, islands, or holes. In our experience, the obtained LB crystals take 1
      10 d to prepare and they are more ordered and radiation stable as compared with
      those produced using other crystallization methods.

PMID- 29189771
TI  - Chemical synthesis of membrane proteins by the removable backbone modification
      method.
AB  - Chemical synthesis can produce membrane proteins bearing specifically designed
      modifications (e.g., phosphorylation, isotope labeling) that are difficult to
      obtain through recombinant protein expression approaches. The resulting
      homogeneously modified synthetic membrane proteins are valuable tools for many
      advanced biochemical and biophysical studies. This protocol describes the
      chemical synthesis of membrane proteins by condensation of transmembrane peptide
      segments through native chemical ligation. To avoid common problems encountered
      due to the poor solubility of transmembrane peptides in almost any solvent, we
      describe an effective procedure for the chemical synthesis of membrane proteins
      through the removable-backbone modification (RBM) strategy. Two key steps of this
      protocol are: (i) installation of solubilizing Arg4-tagged RBM groups into the
      transmembrane peptides at any primary amino acid through Fmoc (9
      fluorenylmethyloxycarbonyl) solid-phase peptide synthesis and (ii) native
      ligation of the full-length sequence, followed by removal of the RBM tags by TFA
      (trifluoroacetic acid) cocktails to afford the native protein. The installation
      of RBM groups is achieved by using 4-methoxy-5-nitrosalicyladehyde by reduction
      amination to incorporate an activated O-to-N acyl transfer auxiliary. The Arg4
      tag-modified membrane-spanning peptide segments behave like water-soluble
      peptides to facilitate their purification, ligation and mass characterization.

PMID- 29189772
TI  - Production of knock-in mice in a single generation from embryonic stem cells.
AB  - The system-level identification and analysis of molecular networks in mammals can
      be accelerated by 'next-generation' genetics, defined as genetics that does not
      require crossing of multiple generations of animals in order to achieve the
      desired genetic makeup. We have established a highly efficient procedure for
      producing knock-in (KI) mice within a single generation, by optimizing the genome
      editing protocol for KI embryonic stem (ES) cells and the protocol for the
      generation of fully ES-cell-derived mice (ES mice). Using this protocol, the
      production of chimeric mice is eliminated, and, therefore, there is no
      requirement for the crossing of chimeric mice to produce mice that carry the KI
      gene in all cells of the body. Our procedure thus shortens the time required to
      produce KI ES mice from about a year to ~3 months. Various kinds of KI ES mice
      can be produced with a minimized amount of work, facilitating the elucidation of
      organism-level phenomena using a systems biology approach. In this report, we
      describe the basic technologies and protocols for this procedure, and discuss the
      current challenges for next-generation mammalian genetics in organism-level
      systems biology studies.

PMID- 29189773
TI  - Multimodal profiling of single-cell morphology, electrophysiology, and gene
      expression using Patch-seq.
AB  - Neurons exhibit a rich diversity of morphological phenotypes,
      electrophysiological properties, and gene-expression patterns. Understanding how
      these different characteristics are interrelated at the single-cell level has
      been difficult because of the lack of techniques for multimodal profiling of
      individual cells. We recently developed Patch-seq, a technique that combines
      whole-cell patch-clamp recording, immunohistochemistry, and single-cell RNA
      sequencing (scRNA-seq) to comprehensively profile single neurons from mouse brain
      slices. Here, we present a detailed step-by-step protocol, including
      modifications to the patching mechanics and recording procedure, reagents and
      recipes, procedures for immunohistochemistry, and other tips to assist
      researchers in obtaining high-quality morphological, electrophysiological, and
      transcriptomic data from single neurons. Successful implementation of Patch-seq
      allows researchers to explore the multidimensional phenotypic variability among
      neurons and to correlate gene expression with phenotype at the level of single
      cells. The entire procedure can be completed in ~2 weeks through the combined
      efforts of a skilled electrophysiologist, molecular biologist, and
      biostatistician.

PMID- 29189774
TI  - Deriving genotypes from RAD-seq short-read data using Stacks.
AB  - Restriction site-associated DNA sequencing (RAD-seq) allows for the genome-wide
      discovery and genotyping of single-nucleotide polymorphisms in hundreds of
      individuals at a time in model and nonmodel species alike. However, converting
      short-read sequencing data into reliable genotype data remains a nontrivial task,
      especially as RAD-seq is used in systems that have very diverse genomic
      properties. Here, we present a protocol to analyze RAD-seq data using the Stacks
      pipeline. This protocol will be of use in areas such as ecology and population
      genetics. It covers the assessment and demultiplexing of the sequencing data,
      read mapping, inference of RAD loci, genotype calling, and filtering of the
      output data, as well as providing two simple examples of downstream biological
      analyses. We place special emphasis on checking the soundness of the procedure
      and choosing the main parameters, given the properties of the data. The procedure
      can be completed in 1 week, but determining definitive methodological choices
      will typically take up to 1 month.

PMID- 29189776
TI  - Mild oxidation of methane to methanol or acetic acid on supported isolated
      rhodium catalysts.
AB  - An efficient and direct method of catalytic conversion of methane to liquid
      methanol and other oxygenates would be of considerable practical value. However,
      it remains an unsolved problem in catalysis, as typically it involves expensive
      or corrosive oxidants or reaction media that are not amenable to
      commercialization. Although methane can be directly converted to methanol using
      molecular oxygen under mild conditions in the gas phase, the process is either
      stoichiometric (and therefore requires a water extraction step) or is too slow
      and low-yielding to be practical. Methane could, in principle, also be
      transformed through direct oxidative carbonylation to acetic acid, which is
      commercially obtained through methane steam reforming, methanol synthesis, and
      subsequent methanol carbonylation on homogeneous catalysts. However, an effective
      catalyst for the direct carbonylation of methane to acetic acid, which might
      enable the economical small-scale utilization of natural gas that is currently
      flared or stranded, has not yet been reported. Here we show that mononuclear
      rhodium species, anchored on a zeolite or titanium dioxide support suspended in
      aqueous solution, catalyse the direct conversion of methane to methanol and
      acetic acid, using oxygen and carbon monoxide under mild conditions. We find that
      the two products form through independent pathways, which allows us to tune the
      conversion: three-hour-long batch-reactor tests conducted at 150 degrees Celsius,
      using either the zeolite-supported or the titanium-dioxide-supported catalyst,
      yield around 22,000 micromoles of acetic acid per gram of catalyst, or around 230
      micromoles of methanol per gram of catalyst, respectively, with selectivities of
      60-100 per cent. We anticipate that these unusually high activities, despite
      still being too low for commercial application, may guide the development of
      optimized catalysts and practical processes for the direct conversion of methane
      to methanol, acetic acid and other useful chemicals.

PMID- 29189777
TI  - Halogens in chondritic meteorites and terrestrial accretion.
AB  - Volatile element delivery and retention played a fundamental part in Earth's
      formation and subsequent chemical differentiation. The heavy halogens-chlorine
      (Cl), bromine (Br) and iodine (I)-are key tracers of accretionary processes owing
      to their high volatility and incompatibility, but have low abundances in most
      geological and planetary materials. However, noble gas proxy isotopes produced
      during neutron irradiation provide a high-sensitivity tool for the determination
      of heavy halogen abundances. Using such isotopes, here we show that Cl, Br and I
      abundances in carbonaceous, enstatite, Rumuruti and primitive ordinary chondrites
      are about 6 times, 9 times and 15-37 times lower, respectively, than previously
      reported and usually accepted estimates. This is independent of the oxidation
      state or petrological type of the chondrites. The ratios Br/Cl and I/Cl in all
      studied chondrites show a limited range, indistinguishable from bulk silicate
      Earth estimates. Our results demonstrate that the halogen depletion of bulk
      silicate Earth relative to primitive meteorites is consistent with the depletion
      of lithophile elements of similar volatility. These results for carbonaceous
      chondrites reveal that late accretion, constrained to a maximum of 0.5 +/- 0.2
      per cent of Earth's silicate mass, cannot solely account for present-day
      terrestrial halogen inventories. It is estimated that 80-90 per cent of heavy
      halogens are concentrated in Earth's surface reservoirs and have not undergone
      the extreme early loss observed in atmosphere-forming elements. Therefore, in
      addition to late-stage terrestrial accretion of halogens and mantle degassing,
      which has removed less than half of Earth's dissolved mantle gases, the efficient
      extraction of halogen-rich fluids from the solid Earth during the earliest stages
      of terrestrial differentiation is also required to explain the presence of these
      heavy halogens at the surface. The hydropilic nature of halogens, whereby they
      track with water, supports this requirement, and is consistent with volatile-rich
      or water-rich late-stage terrestrial accretion.

PMID- 29189775
TI  - Visualizing endocytic recycling and trafficking in live neurons by
      subdiffractional tracking of internalized molecules.
AB  - Our understanding of endocytic pathway dynamics is restricted by the diffraction
      limit of light microscopy. Although super-resolution techniques can overcome this
      issue, highly crowded cellular environments, such as nerve terminals, can also
      dramatically limit the tracking of multiple endocytic vesicles such as synaptic
      vesicles (SVs), which in turn restricts the analytical dissection of their
      discrete diffusional and transport states. We recently introduced a pulse-chase
      technique for subdiffractional tracking of internalized molecules (sdTIM) that
      allows the visualization of fluorescently tagged molecules trapped in individual
      signaling endosomes and SVs in presynapses or axons with 30- to 50-nm
      localization precision. We originally developed this approach for tracking single
      molecules of botulinum neurotoxin type A, which undergoes activity-dependent
      internalization and retrograde transport in autophagosomes. This method was then
      adapted to localize the signaling endosomes containing cholera toxin subunit-B
      that undergo retrograde transport in axons and to track SVs in the crowded
      environment of hippocampal presynapses. We describe (i) the construction of a
      custom-made microfluidic device that enables control over neuronal orientation;
      (ii) the 3D printing of a perfusion system for sdTIM experiments performed on
      glass-bottom dishes; (iii) the dissection, culturing and transfection of
      hippocampal neurons in microfluidic devices; and (iv) guidance on how to perform
      the pulse-chase experiments and data analysis. In addition, we describe the use
      of single-molecule-tracking analytical tools to reveal the average and the
      heterogeneous single-molecule mobility behaviors. We also discuss alternative
      reagents and equipment that can, in principle, be used for sdTIM experiments and
      describe how to adapt sdTIM to image nanocluster formation and/or tubulation in
      early endosomes during sorting events. The procedures described in this protocol
      take ~1 week.

PMID- 29189778
TI  - Probing many-body dynamics on a 51-atom quantum simulator.
AB  - Controllable, coherent many-body systems can provide insights into the
      fundamental properties of quantum matter, enable the realization of new quantum
      phases and could ultimately lead to computational systems that outperform
      existing computers based on classical approaches. Here we demonstrate a method
      for creating controlled many-body quantum matter that combines deterministically
      prepared, reconfigurable arrays of individually trapped cold atoms with strong,
      coherent interactions enabled by excitation to Rydberg states. We realize a
      programmable Ising-type quantum spin model with tunable interactions and system
      sizes of up to 51 qubits. Within this model, we observe phase transitions into
      spatially ordered states that break various discrete symmetries, verify the high
      fidelity preparation of these states and investigate the dynamics across the
      phase transition in large arrays of atoms. In particular, we observe robust many
      body dynamics corresponding to persistent oscillations of the order after a rapid
      quantum quench that results from a sudden transition across the phase boundary.
      Our method provides a way of exploring many-body phenomena on a programmable
      quantum simulator and could enable realizations of new quantum algorithms.

PMID- 29189779
TI  - Erratum: Enhanced sensitivity at higher-order exceptional points.
AB  - This corrects the article DOI: 10.1038/nature23280.

PMID- 29189782
TI  - What makes teams tick.

PMID- 29189781
TI  - Observation of a many-body dynamical phase transition with a 53-qubit quantum
      simulator.
AB  - A quantum simulator is a type of quantum computer that controls the interactions
      between quantum bits (or qubits) in a way that can be mapped to certain quantum
      many-body problems. As it becomes possible to exert more control over larger
      numbers of qubits, such simulators will be able to tackle a wider range of
      problems, such as materials design and molecular modelling, with the ultimate
      limit being a universal quantum computer that can solve general classes of hard
      problems. Here we use a quantum simulator composed of up to 53 qubits to study
      non-equilibrium dynamics in the transverse-field Ising model with long-range
      interactions. We observe a dynamical phase transition after a sudden change of
      the Hamiltonian, in a regime in which conventional statistical mechanics does not
      apply. The qubits are represented by the spins of trapped ions, which can be
      prepared in various initial pure states. We apply a global long-range Ising
      interaction with controllable strength and range, and measure each individual
      qubit with an efficiency of nearly 99 per cent. Such high efficiency means that
      arbitrary many-body correlations between qubits can be measured in a single shot,
      enabling the dynamical phase transition to be probed directly and revealing
      computationally intractable features that rely on the long-range interactions and
      high connectivity between qubits.

PMID- 29189783
TI  - Put safety first.

PMID- 29189780
TI  - A semi-synthetic organism that stores and retrieves increased genetic
      information.
AB  - Since at least the last common ancestor of all life on Earth, genetic information
      has been stored in a four-letter alphabet that is propagated and retrieved by the
      formation of two base pairs. The central goal of synthetic biology is to create
      new life forms and functions, and the most general route to this goal is the
      creation of semi-synthetic organisms whose DNA harbours two additional letters
      that form a third, unnatural base pair. Previous efforts to generate such semi
      synthetic organisms culminated in the creation of a strain of Escherichia coli
      that, by virtue of a nucleoside triphosphate transporter from Phaeodactylum
      tricornutum, imports the requisite unnatural triphosphates from its medium and
      then uses them to replicate a plasmid containing the unnatural base pair dNaM
      dTPT3. Although the semi-synthetic organism stores increased information when
      compared to natural organisms, retrieval of the information requires in vivo
      transcription of the unnatural base pair into mRNA and tRNA, aminoacylation of
      the tRNA with a non-canonical amino acid, and efficient participation of the
      unnatural base pair in decoding at the ribosome. Here we report the in vivo
      transcription of DNA containing dNaM and dTPT3 into mRNAs with two different
      unnatural codons and tRNAs with cognate unnatural anticodons, and their efficient
      decoding at the ribosome to direct the site-specific incorporation of natural or
      non-canonical amino acids into superfolder green fluorescent protein. The results
      demonstrate that interactions other than hydrogen bonding can contribute to every
      step of information storage and retrieval. The resulting semi-synthetic organism
      both encodes and retrieves increased information and should serve as a platform
      for the creation of new life forms and functions.

PMID- 29189784
TI  - China to roll back regulations for traditional medicine despite safety concerns.

PMID- 29189785
TI  - United Kingdom relies on science to revive flagging economy.

PMID- 29189786
TI  - How to mobilize group intelligence.

PMID- 29189788
TI  - Illicit gene therapies, forensic data and Australia's water woes.

PMID- 29189787
TI  - 'Alien' DNA makes proteins in living cells for the first time.

PMID- 29189789
TI  - AI-controlled brain implants for mood disorders tested in people.

PMID- 29189790
TI  - Energy transitions.

PMID- 29189791
TI  - The microscope makers.

PMID- 29189792
TI  - The next step on the energy ladder.

PMID- 29189793
TI  - Traditional Chinese medicine needs proper scrutiny.

PMID- 29189794
TI  - A day in the life of a cell biologist.

PMID- 29189795
TI  - Large quantum systems tamed.

PMID- 29189798
TI  - Five ways to fix statistics.

PMID- 29189796
TI  - London scientists feel the noise.

PMID- 29189799
TI  - Supercomputing poised for a massive speed boost.

PMID- 29189801
TI  - Methane upgraded by rhodium.

PMID- 29189803
TI  - Make low-carbon energy an integral part of the knowledge economy.

PMID- 29189802
TI  - Opiate deaths demand serious action.

PMID- 29189805
TI  - Corrections.

PMID- 29189804
TI  - Research papers: Lifetime word limits would unleash woe.

PMID- 29189806
TI  - Energize the people to effect policy change.

PMID- 29189807
TI  - Blood boosts bids to unpick membrane science.

PMID- 29189808
TI  - Turning point: Empathetic outreach.

PMID- 29189809
TI  - Trophy hunting: Science on its own can't dictate policy.

PMID- 29189810
TI  - Power through the ages.

PMID- 29189811
TI  - Gilbert Stork (1921-2017).

PMID- 29189812
TI  - Pro-science budget is not enough for a Brexit world.

PMID- 29189813
TI  - How chromosomes unite.

PMID- 29189814
TI  - Landmark contributions: Credit pioneer in plate tectonics.

PMID- 29189815
TI  - Contactless health-care sensing.

PMID- 29189816
TI  - Clinical records: Thirty years of Dutch embryo selection.

PMID- 29189817
TI  - The complex web behind the siting of power plants.

PMID- 29189818
TI  - How social scientists can help to shape climate policy.

PMID- 29189819
TI  - The real cost of energy.

PMID- 29189821
TI  - ?

PMID- 29189822
TI  - [Cognitive traps and clinical decisions].
AB  - We are fallible, we have limited computational capabilities, limited access to
      information, little memory. Moreover, in everyday life, we feel joy, fear, anger,
      and other emotions that influence our decisions in a little, "calculated" way.
      Not everyone, however, is also aware that the mistakes we make are often
      systematic and therefore, in particular circumstances, are foreseeable. Doctors
      and patients are constantly called upon to make decisions. They need to identify
      relevant information (for example, the symptoms or outcome of an examination),
      formulate a judgment (for example a diagnosis), choose an action course among the
      various possible ones based on one's own preferences (e.g. medication or
      surgery), so act. The exact size of the medical error is unknown, but probably
      huge. In fact, the more we investigate and the more we find. Often these mistakes
      depend on the cognitive process. Any (rational) decision requires, in particular,
      an assessment of the possible effects of the action it implements; for example
      how much pleasure or pain it will cause us. In the medical field, too, the
      principle of informed consent provides that the patient's preferences and values
      are to guide clinical choices. Yet, not always the preferences that people
      express before making an experience match with their preferences after living
      that experience. Some ingenious experiments suggest (in a seemingly paradoxical
      way) that before a direct experience, people prefer less pain; after that
      experience they prefer more, but with a better memory.

PMID- 29189823
TI  - [The SURTAVI study].

PMID- 29189824
TI  - [From the origins to the SYNTAX study: 50 years (and more) of coronary artery
      bypass grafting].

PMID- 29189820
TI  - Somatic TP53 variants frequently confound germ-line testing results.
AB  - PURPOSE: Blood/saliva DNA is thought to represent the germ line in genetic cancer
      risk assessment. Cases with pathogenic TP53 variants detected by multigene panel
      testing are often discordant with Li-Fraumeni syndrome, raising concern about
      misinterpretation of acquired aberrant clonal expansions (ACEs) with TP53
      variants as germ-line results. METHODS: Pathogenic TP53 variants with abnormal
      next-generation sequencing metrics (e.g., decreased ratio (<25%) of mutant to
      wild-type allele, more than two detected alleles) were selected from a CLIA
      laboratory testing cohort. Alternate tissues and/or close relatives were tested
      to distinguish between ACE and germ-line status. Clinical data and Li-Fraumeni
      syndrome testing criteria were examined. RESULTS: Among 114,630 multigene panel
      tests and 1,454 TP53 gene-specific analyses, abnormal next-generation sequencing
      metrics were observed in 20% of 353 TP53-positive results, and ACE was confirmed
      for 91% of cases with ancillary materials, most of these due to clonal
      hematopoiesis. Only four met Chompret criteria. Individuals with ACE were older
      (50 years vs. 33.7; P = 0.02) and were identified more frequently in multigene
      panel tests (66/285; 23.2%) than in TP53 gene-specific tests (6/68; 8.8%, P =
      0.005). CONCLUSION: ACE confounds germ-line diagnosis, may portend hematologic
      malignancy, and may provoke unwarranted clinical interventions. Ancillary testing
      to confirm germ-line status should precede Li-Fraumeni syndrome management.

PMID- 29189825
TI  - [Appropriateness and surroundings: "Doing more does not mean doing better".
      Choosing Wisely, an unfulfilled commitment?]
AB  - The attention of the medical community to the appropriateness of diagnostic and
      therapeutic procedures has increased in recent years, recognizing the need for a
      careful use of resources and for avoiding unnecessary and sometimes harmful
      medical tests, procedures and therapies. Not only healthcare providers, but also
      public, patients and politicians, should know the consequences of inappropriate
      decisions and behaviors. Indeed, inappropriateness has clinical (risks), economic
      (waste of resources), but also ethical implications (i.e. the use of unnecessary
      tests and treatments in a system characterized by limited
      resources).Inappropriateness is a complex entity and it may vary widely: in fact,
      it may be influenced by different clinical settings, techniques used, but also by
      data collection methods, size of the population considered, and the professional
      background of the physicians requesting a specific test or procedure.Various
      initiatives have been proposed with the aim at reducing the use of unnecessary
      tests and procedures but imposed rules appear to be of dubious effectiveness. On
      the contrary, the medical community needs more in-depth knowledge of the problem
      and an active commitment for reducing the waste of resources, especially because
      unnecessary or sometimes harmful interventions subtract resources where they are
      useful or necessary.Recently, the "Choosing Wisely" campaign, which has involved
      18 countries and more than 70 scientific societies, has been one of the most well
      known initiatives, launched in Italy by the "Slow Medicine" movement. The purpose
      is to disseminate the recommendations of scientific societies with the aim to
      promote processes of care based on appropriateness, but within a relation of
      dialogue and decision sharing with the patient and public.The Choosing Wisely
      campaign is certainly important and innovative. However, there are open and
      unsolved issues such as the lack of rigorous and systematic methods for the
      evaluation of the results of the proposed initiatives and the need for more
      widespread interventions both at the medical and community level.

PMID- 29189826
TI  - [Cardiology: is the smartphone era?]
AB  - The worldwide spread of smartphones has radically changed the habits of human
      life, allowing a 24/7 connection with other people. These changes have involved
      also Medicine with smartphones being able to simplify the clinical practice of
      physicians. The development of new external devices that can be connected to
      smartphones has further increased their use with mobile phones converted in
      portable electrocardiogram or echocardiogram machines. This extraordinary
      technological improvement seems to be partly in conflict with the classical tools
      available for the cardiologist, such as the "old" stethoscope that in 2016 had
      its 200th anniversary. This article focuses on the smartphone as a new tool
      available for the physicians, describing the most important potential uses and
      reporting an analysis of pros and cons of the smart-cardiology.

PMID- 29189827
TI  - [Coronary microvascular dysfunction: past, present, and future of an evolving
      disease].
AB  - Coronary atherosclerosis is the main cause of myocardial ischemia. Nevertheless
      10-30% of patients with angina has angiographically normal coronary arteries. In
      the last 30 years, several studies showed that in these patients the symptoms can
      be caused by dysfunction of the coronary microcirculation. Coronary microvascular
      dysfunction (CMVD) occurring in patients affected by specific cardiac or systemic
      diseases may be due to mechanisms of the underlying disease. On the other hand,
      in several patients affected by angina with angiographically normal coronary
      arteries, there is no specific disease, and CMVD only is responsible for the
      clinical picture. This condition can be defined as leading microvascular angina
      in order to distinguish it from other forms of microvascular angina where CMVD is
      related to the presence of a specific disease. As regards pathogenesis, there are
      still many uncertainties, though evidence suggesting a role for certain risk
      factors rather than others is gradually emerging, along with the demonstration of
      new alterations of endothelial function. Also as regards therapy, and prognosis
      above all, the debate is still open.

PMID- 29189828
TI  - [Coronary revascularization in patients with ST-elevation myocardial infarction
      and multivessel disease].
AB  - Forty to 60% of ST-elevation myocardial infarction (STEMI) patients present with
      multivessel coronary artery disease, identified during primary percutaneous
      coronary intervention (pPCI) of the culprit lesion. At present, data about
      revascularization of non-culprit coronary lesions are conflicting. Nevertheless,
      patients with multivessel coronary artery disease have a worse outcome. Recently,
      several randomized controlled trials and meta-analyses compared a strategy of
      culprit-only revascularization vs complete revascularization (during pPCI or
      staged PCI of the non-culprit lesion). The majority of data show a potential
      benefit of complete revascularization, in particular a reduction in the composite
      endpoint of major adverse cardiac events, in absence of certain data regarding
      long-term mortality and reinfarction. Besides, it is still controversial the
      optimal timing of complete revascularization (during pPCI or staged PCI), as well
      as the best method for evaluating the lesions to be treated (angiographic vs
      functional assessment of ischemia). Considering all these data, the only tested
      and safe approach to treat multivessel coronary artery disease patients remains
      optimization of medical therapy with long-term prescription of newer antiplatelet
      agents (ticagrelor and prasugrel) and aggressive lipid-lowering therapy (LDL <70
      mg/dl). At the same time, a complete coronary revascularization strategy with
      PCI, especially guided by ischemia and based on patient lesions and comorbidity,
      may further improve outcomes.

PMID- 29189829
TI  - [Oral combination therapy for the treatment of patients with pulmonary arterial
      hypertension: what evidence from long-term studies?]
AB  - The introduction of specific drugs for the treatment of pulmonary arterial
      hypertension over the last 20 years has led to an improvement of clinical and
      hemodynamic conditions and prognosis of affected patients. The use of combination
      therapy has made it possible to act simultaneously on several biological pathways
      involved in the etiopathogenesis of the disease. However, although the diagnosis
      and management have radically changed in recent years, the disease remains
      progressive and often fatal. The purpose of this paper is to review and discuss
      the results of the main clinical trials and the future perspectives of
      combination strategies for the treatment of pulmonary arterial hypertension.

PMID- 29189830
TI  - [Ambulatory cardiac rehabilitation in Trieste: protocols of intervention,
      activities and outcomes].
AB  - BACKGROUND: Cardiac rehabilitation (CR) is a model of care proven to reduce
      mortality and morbidity in patients with coronary artery disease. The aim of this
      study is to describe the ambulatory CR model of the Cardiovascular Department of
      Trieste (Italy), analyzing the outcome of the population. METHODS: We analyzed
      clinical and instrumental characteristics of all consecutive patients after ST
      elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction
      (NSTEMI), coronary artery bypass graft with or without valve surgery
      (CABG/CABGV), or planned percutaneous coronary intervention (PCI), referred for
      CR from January 1, 2009, to December 31, 2015. All patients were included in a
      registry. During CR and at 1-year follow-up, the incidence of new
      hospitalizations due to cardiovascular causes was assessed. Total and
      cardiovascular mortality was also evaluated at longer follow-up. RESULTS:
      Overall, 3088 patients (28% female, mean age 70 +/- 11 years; 35% older than 75
      years) were referred for CR, 30% after STEMI, 23% after NSTEMI, 29% after
      CABG/CABGV, and 19% after PCI. At enrollment, 9% of patients had an ejection
      fraction <40%, 76% were hypertensive, 61% dyslipidemic, 19% diabetics, and 27%
      smokers. CR lasted 5 +/- 4 months. At the end of the CR program, 96% of patients
      were on antiplatelets, 79% on beta-blockers, 73% on angiotensin-converting enzyme
      inhibitors, 25% on angiotensin II receptor blockers, and 87% on statins with
      achievement of the following secondary prevention targets: LDL cholesterol 85 +/-
      30 mg/dl, glycated hemoglobin 7.2 +/- 4%, heart rate 64 +/- 11 bpm,
      systolic/diastolic blood pressure 137 +/- 32/78 +/- 14 mmHg. During CR, new
      hospitalizations occurred in 11% of patients, 1% within 1 year after CR. At a
      mean follow-up of 4.4 +/- 2 years, 11% of patients died, 3% for cardiovascular
      causes, 0.7% within 1 year. Cardiovascular mortality was significantly higher in
      elderly patients (6 vs 2%, p=0.000), women (4 vs 3%, p=0.038), diabetics (5 vs
      3%, p=0.004), and in patients with left ventricular dysfunction (8 vs 3%,
      p=0.000). CONCLUSIONS: Our findings show the feasibility of a CR program in an
      unselected population, characterized by advanced age, risk factors and
      comorbidities. A critical analysis of the registry data allowed us to achieve
      good results in secondary prevention and outcomes.

PMID- 29189831
TI  - [Newer generation self-expandable coronary stent bail-out re-sheathing].
AB  - Newer generation of self-expandable nitinol coronary stents has proven to be
      useful in the treatment of bifurcations, tapered vessels, thrombotic lesions,
      venous grafts and ectatic segments. However, optimal device positioning can be
      cumbersome, due to the peculiar delivery mechanism which consists of retracting
      an outer sheath in order to release the stent from the distal edge. We report the
      case of a 53-year-old man, admitted for unstable angina. Coronary angiography
      showed a tight stenosis of the proximal left anterior descending coronary artery.
      As the lesion was located in an ectatic segment of the vessel, we chose to
      implant a StentysTM (Stentys S.A., Paris, France) device. During the release, the
      stent jumped forward, resulting in geographic miss. We describe the technique
      used to retrieve the stent and how we re-deployed it in the proper position;
      moreover, we examine the lesion characteristics which fostered the migration of
      the self-apposing stent along the vessel.

PMID- 29189833
TI  - [Prof. Bruno Magnani].

PMID- 29189832
TI  - [Peripheral embolization and rapid growth of papillary fibroelastoma in a young
      woman].
AB  - Papillary fibroelastoma, a benign cardiac tumor, is a rare clinical condition.
      Before the echocardiography era, the diagnosis was often occasional, especially
      during other cardiac procedures; but nowadays it has improved with the advent of
      higher-resolution imaging technology. The clinical presentation can vary from
      asymptomatic to severe complications such as cerebrovascular or ischemic events
      due to tumor embolization.We present the case of a 33-year-old female with a
      papillary fibroelastoma on the anterior leaflet of the mitral valve undergoing
      clinical examination for claudicatio intermittens. An occlusion of the left
      common femoral artery was present. The diagnosis was made posteriorly after
      embolectomy. All cardiac imaging investigations were negative. The heart team
      decided a strict echocardiographic follow-up every 3 months, and after the first
      visit a pedunculated mass was detected on the anterior mitral leaflet. The
      surgical management included urgent resection of the tumor on cardiopulmonary
      bypass using a minimally invasive approach via a right anterior minithoracotomy.
      The postoperative course was uneventful. We emphasize the need for surgical
      treatment given the potential risk of relapse. When no mass is detected on
      imaging, a strict echocardiographic follow-up and antiplatelet therapy are
      mandatory.

PMID- 29189836
TI  - Practical synthesis of pharmaceutically relevant molecules enriched in sp3
      character.
AB  - The expedient synthesis of compounds enriched in sp3 character is key goal in
      modern drug discovery. Herein, we report how a single pot Suzuki-Miyaura
      hydrogenation can be used to furnish lead and fragment-like products in good to
      excellent yields. The approach has been successfully applied in formats amenable
      to parallel synthesis, in an asymmetric sense, and in the preparation of
      molecules with annotated biological activity.

PMID- 29189834
TI  - In trans hydrolysis of carrier protein-bound acyl intermediates by CitA during
      citrinin biosynthesis.
AB  - Polyketide synthases (PKSs) have several known editing mechanisms to ensure that
      non-productive intermediates are removed from the acyl carrier protein (ACP). We
      demonstrate that CitA, a putative hydrolase in the citrinin biosynthetic gene
      cluster, removes ACP-bound acyl intermediates. We propose that it serves an
      editing role in trans.

PMID- 29189837
TI  - Theoretical interpretation of Warburg's impedance in unsupported electrolytic
      cells.
AB  - We discuss the origin of Warburg's impedance in unsupported electrolytic cells
      containing only one group of positive and one group of negative ions. Our
      analysis is based on the Poisson-Nernst-Planck model, where the generation
      recombination phenomenon is neglected. We show that to observe Warburg-like
      impedance the diffusion coefficient of the positive ions has to differ from that
      of the negative ones, and furthermore the electrodes have to be not blocking. We
      assume that the non-blocking properties of the electrodes can be described by
      means of an Ohmic model, where the charge exchange between the cell and the
      external circuit is described by means of an electrode conductivity. For
      simplicity we consider a symmetric cell. However, our analysis can be easily
      generalized to more complicated situations, where the cell is not symmetric and
      the charge exchange is described by the Chang-Jaffe model, or by a linearized
      version of the Butler-Volmer equation. Our analysis allows justification of the
      expression for Warburg's impedance proposed previously by several groups, based
      on wrong assumptions.

PMID- 29189838
TI  - An engineered cell-imprinted substrate directs osteogenic differentiation in stem
      cells.
AB  - A cell-imprinted poly(dimethylsiloxane)/hydroxyapatite nanocomposite substrate
      was fabricated to engage topographical, mechanical, and chemical signals to
      stimulate and boost stem cell osteogenic differentiation. The physicochemical
      properties of the fabricated substrates, with nanoscale resolution of osteoblast
      morphology, were probed using a wide range of techniques including scanning
      electron microscopy, atomic force microscopy, dynamic mechanical thermal
      analysis, and water contact angle measurements. The osteogenic differentiation
      capacity of the cultured stem cells on these substrates was probed by alizarin
      red staining, ALP activity, osteocalcin measurements, and gene expression
      analysis. The outcomes revealed that the concurrent roles of the surface patterns
      and viscoelastic properties of the substrate provide the capability of directing
      stem cell differentiation toward osteogenic phenotypes. Besides the physical and
      mechanical effects, we found that the chemical signaling of osteoinductive
      hydroxyapatite nanoparticles, embedded in the nanocomposite substrates, could
      further improve and optimize stem cell osteogenic differentiation.

PMID- 29189840
TI  - Hydrogen sorption efficiency of titanium decorated calix[4]pyrroles.
AB  - Hydrogen is a promising and the most environmentally friendly energy carrier due
      to its renewable nature and it is expected to replace fossil fuels. The hydrogen
      storage properties of Ti decorated calix[4]pyrrole (CXP) and
      octamethylcalix[4]pyrrole (MeCXP) have been reported. The structure, stability
      and hydrogen loading efficiency of Ti decorated CXP and MeCXP have been studied
      based on density functional theory with the Minnesota 06 (M06) functional and the
      6-311G(d,p) basis set. Ti binds with the pyrrole rings of CXP and MeCXP from
      outside of each ring by Dewar coordination. It is found that Ti decorated CXP and
      MeCXP have hydrogen wt% 9.7 and 10.5 respectively. The usable hydrogen wt% is
      found to be 6.35 and 5.20 for CXP and MeCXP respectively. The stability of Ti
      decorated CXP and MeCXP is studied by calculating global reactivity parameters,
      which follow maximum hardness and minimum philicity principles. The calculated
      adsorption and desorption energy values are found to be low and decrease on H2
      adsorption in both the Ti decorated systems. The molecular dynamics simulations
      indicate that the hydrogen starts releasing at 273 K and all the hydrogen
      molecules are released by 473 K from both the systems. These predictions pave the
      way to reversibly store hydrogen efficiently with high gravimetric storage
      capacity in CXP and MeCXP systems.

PMID- 29189841
TI  - Probing electron transfer between hemin and riboflavin using a combination of
      analytical approaches and theoretical calculations.
AB  - Extracellular electron transfer (EET) occurs from outer-membrane proteins to
      electron acceptors. Heme(ii) is the active center of outer-membrane proteins and
      delivers electrons to acceptors or mediators such as riboflavin, a redox active
      chromophore present in organisms. However, the EET mechanism via mediators,
      especially the electron transfer process from outer-membrane proteins to
      mediators, has not been well documented yet. In this work, the mechanism behind
      the electron transfer from heme(ii) to riboflavin is investigated by using in
      situ ultraviolet visible and fluorescence spectroelectrochemical analysis, which
      provides the information regarding the structural change and electrochemical
      characteristics of species in the electron transfer process. It is found that
      hemin(iii), the oxidized form of heme(ii), is electrolyzed to an intermediate
      "hemx(ii)" without structural changes, and is then transformed to heme(ii) by
      conjugating with riboflavin and its radicals. Heme(ii) is able to activate
      riboflavin reduction via a two-electron two-proton pathway in aqueous solution.
      The mechanisms proposed on the basis of experimental results are further
      confirmed by density functional theory calculations. The results about the
      electron transfer from hemx(ii) (or heme(ii)) to riboflavin are useful not only
      for understanding the EET mechanisms, but also for maximizing the role of
      riboflavin in biogeochemical cycling and environmental bioremediation.

PMID- 29189843
TI  - Solvent polarity and oxygen sensitivity, rather than viscosity, determine
      lifetimes of biaryl-sensitised terbium luminescence.
AB  - In a macrocyclic terbium complex incorporating a biaryl sensitiser, the observed
      variation of emission lifetime is shown to be determined by the solubility of
      oxygen in the solvent system and the relative energy of the chromophore excited
      state, rather than any dependence on solvent viscosity.

PMID- 29189847
TI  - Theoretical exploration of the potential applications of Sc-based MXenes.
AB  - Herein, we systematically explored the electronic properties of Sc-based MXenes
      via first-principles calculations, with the aim to extend their applicability. OH
      Functionalized carbides and OH/SH-terminated nitrides manifest ultralow work
      functions, potential in field-effect transistors. Furthermore, we identified
      three novel semiconductors (Sc2CCl2, Sc2C(SH)2, and Sc2NO2). Specifically, Sc2NO2
      is a spin gapless semiconductor, promising for spintronics. Type-II
      heterojunctions are readily available between Sc-based semiconducting MXenes,
      facilitating charge separation for optoelectronics and solar energy conversion.
      Further photocatalytic analysis indicates that Sc2CCl2 is capable of oxidizing
      H2O into O2.

PMID- 29189851
TI  - Plasmon-mediated cancer phototherapy: the combined effect of thermal and
      photodynamic processes.
AB  - A nanoplatform for simultaneous cellular imaging, and photodynamic and
      photothermal therapies has been designed and realized by embedding a purposely
      synthesized highly luminescent water soluble iridium(iii) compound into gold core
      silica shell nanoparticles. These multifunctionalities arise mainly from the
      photophysical properties of the cyclometalated complex: (i) the heavy atom
      promotes, through excited triplet state formation, energy transfer processes
      towards molecular oxygen, with the generation of 1O2 (photodynamic effect); (ii)
      the overlap of the iridium(iii) complex emission band with the plasmonic
      resonance of gold nanostructures allows excitation energy transfer towards the
      metallic core (photothermal effect); (iii) the remarkable iridium(iii) complex
      luminescence feature, which is preserved despite energy transfer processes, makes
      the whole system an efficient luminescent bio-probe (imaging). Photophysical and
      photothermal investigations have been carried out, whereas in vitro photo
      cytotoxicity tests have been performed on human glioblastoma cells (U87MG),
      highlighting significant cancer cell death at a very low photosensitizer
      concentration (<0.5 MUM), by means of a synergistic photodynamic and photothermal
      effect.

PMID- 29189852
TI  - Assessment of left atrial function in patients with type 2 diabetes mellitus with
      a disease duration of six months.
AB  - INTRODUCTION: Changes in left atrial (LA) size and function are associated with
      adverse clinical events. Recently, duration of diabetes mellitus (DM2) has been
      found to be positively associated with increased LA volume and impaired LA
      function. This study was performed, using two-dimensional echocardiograpy, to
      evaluate the changes in LA volume and function in patients with DM2 with a
      disease duration of six months, and to assess the parameters that affect LA
      volume and function. METHODS: Fifty-six patients (28 male, age: 52.6 +/- 6.5
      years) with DM2 and 56 controls (24 male; age: 50.1 +/- 7.0 years) were enrolled
      in the study. Each subject underwent conventional two-dimensional
      echocardiography to assess LA volume (indexed maximal LA volume: Vmax, pre-atrial
      contraction volume: Volp, minimal LA volume: Vmin) and LA function [passive
      emptying volume - passive emptying fraction (PEV - PEF), active emptying volume -
      active emptying fraction (AEV - AEF), total emptying volume - total emptying
      fraction (TEV - TEF) ]. RESULTS: LA diameter, indexed Vmax, Volp, Vmin, AEV and
      TEV were found to be significantly higher in the DM2 group compared with the
      controls (p < 0.05). Indexed Vmax, Volp and Vmin were significantly correlated
      with HbA1c level, body mass index (BMI), high-sensitivity C-reactive protein and
      uric acid levels, mitral A wave, E/E' ratio and A' wave. According to
      multivariate analysis, age and BMI had a statistically significant effect on LA
      volume. CONCLUSION: Impaired LA function may be present in patients with newly
      diagnosed DM2. BMI and increasing age caused LA enlargement and LA volumes that
      were independent of the effects of hypertension and DM2.

PMID- 29189853
TI  - [Features, management and prognosis of Chilean patients with non valvular atrial
      fibrillation: GARFIELD AF registry].
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is
      associated with high rates of death, ischemic stroke and systemic embolism (SE).
      There is scarce information about clinical characteristics and use of anti
      thrombotic therapies in Chilean patients with non-valvular AF. AIM: To describe
      the characteristics and 1-year outcomes of patients with recently diagnosed AF
      recruited in Chile into the prospective global GARFIELD-AF registry. MATERIAL AND
      METHODS: Between 2011-2016, we prospectively registered information of 971
      patients recruited at 15 centers, 85% of them from the public system and 15% from
      the private sector. Demographics, clinical characteristics and use of
      antithrombotic therapies were recorded for all patients. Adverse clinical
      outcomes were analyzed in 711 patients with 1-year follow-up. RESULTS: The mean
      age was 71.5 years (66-79), 50% were men. Mean CHAD2S2 Vasc and HAS BLED scores
      for stroke risk were 3.3 (2.0-4.0) and 1.5 (1.0-2.0) respectively. Oral
      anticoagulants were prescribed in 82% of patients. Seventy percent received
      Vitamin K antagonists, 10% novel direct anticoagulants or antiplatelet therapy
      and only 8% did not receive any antithrombotic therapy. Mean time in optimal
      therapeutic range (an international normalized ratio of 2 to 3), was achieved in
      only 40.7% (23.0-54.8) of patients receiving Vitamin K antagonists. One year
      rates of death, stroke/systemic embolism and bleeding were 4.75 (3.36-6.71), 2.40
      (1.47-3.92) and 1.64% (0.91-2.97) per 100 person-years. Ischemic stroke occurred
      in 1.8% and hemorrhagic stroke in 0.8% of patients at 1-year of follow up.
      CONCLUSIONS: Although the use of vitamin K antagonists at baseline was high, the
      mean time in optimal therapeutic range was low. Mortality and stroke rates are
      higher than those reported in other contemporary registries.

PMID- 29189854
TI  - [Effects of a high intensity interval training on the aerobic capacity of
      adolescents].
AB  - BACKGROUND: If aerobic capacity is stimulated early in life, maximal oxygen
      consumption during adulthood is assured. AIM: To analyze the effects of a high
      intensity interval training (HIIT) in adolescents on the maximal oxygen
      consumption (VO2max) measured using the 20-m shuttle run test (20mSRT). MATERIAL
      AND METHODS: Twenty eight teenagers aged 13 +/- 0.6 years were divided in two
      groups of 14 subjects each. One group was to a 16 sessions of HIIT interval
      training based on their individual maximal aerobic speed and the other continued
      with their usual exercise done at school. At baseline and the end of the
      intervention VO2max was measured using the 20mSTR. RESULTS: At the end of the
      intervention, the trained teenagers significantly improved their VO2max and the
      time spent in the 20mSTR. CONCLUSIONS: A HIIT program based on the individual
      maximal aerobic speed improves VO2max in adolescents.

PMID- 29189855
TI  - [Changes in the clinical presentation of Influenza A H1N1pdm09 after the
      pandemic].
AB  - BACKGROUND: After the 2009 influenza pandemic the H1N1pdm09 strain circulate
      seasonally. In 2015, Puerto Montt Hospital in Chile faced a simultaneous outbreak
      of both seasonal H3N2 and H1N1pdm09 influenza A (IA). AIM: To evaluate the
      clinical differences between the two viral strains and recent changes in the
      behavior of H1N1pdm09 IA. MATERIAL AND METHODS: We set up a retrospective study
      including every adult hospitalized in Puerto Montt Hospital in 2015 due to IA,
      confirmed by reverse transcription polymerase chain reaction. We compared
      epidemiological data, clinical presentation, complications, and the outcome of
      patients with H1N1pdm09 versus those with seasonal influenza. In parallel, we
      compared 62 cases of thatH1N1 IA from 2015 with 100 cases who were hospitalized
      and analyzed in 2009. RESULTS: Between July and October 2015, 119 adults with
      confirmed IA were hospitalized. From 2009 to 2015, the mean age of patients with
      IAH1N1pdm09 increased from 40.4 +/- 17 to 58.8 +/- 16 years (p < 0.01). Pneumonia
      as the cause of hospitalization decreased from 75 to 58% of patients, (p = 0.04).
      Likewise, the presence of comorbidities increased from 53 to 74%, (p < 0.01).
      Compared with seasonal H3N2, patients with IAH1N1pdm09 IA were more likely to
      require intensive care (p < 0.01) and mechanical ventilation (p < 0.01) and
      developed septic shock (p = 0.03). Their mortality was non-significantly higher
      (13 and 5% respectively). CONCLUSIONS: The clinical presentation of H1N1pdm09 IA
      has varied over time and now affects an older population, with a greater number
      of comorbidities. It also appears to be adopting the clinical behavior of a
      classic seasonal influenza virus.

PMID- 29189856
TI  - [The impact of the orthopedic surgeons' attire on patient preferences].
AB  - BACKGROUND: The formal appearance of health care professionals may influence
      their trustworthiness. AIM: To determine the effect of the orthopedic surgeon's
      attire on patients' perceptions of credibility and reliability of professionals.
      MATERIAL AND METHODS: In a cross-sectional design, 351 patients (mean age 43 +/-
      17 years, 62% males) from the Department of Orthopedics and Traumatology of a
      Chilean regional hospital in southem of Chile were chosen to complete a
      questionnaire of attire preferences, in which five photographs with male and
      female orthopedic surgeons appeared (executive, formal attire, informal attire,
      scrubs and casual clothing). The influence of attire in the perception of
      physicians' trustworthiness to resolve medical situations was analyzed. RESULTS:
      Forty four percent of patients had no physician gender predilection (p = 0.32).
      Forty three percent of male and 38% of female patients preferred the use of
      formal attire. In situations of credibility or confidence, all patients chose
      mostly the use of white coats with formal attire by professionals. The
      probability of choosing an orthopedic surgeon with a formal attire was
      significantly higher among patients who considered the attire and appearance of
      the professional to be very important (Odds ratio = 3.74; p < 0.01). CONCLUSIONS:
      Patients prefer orthopedic surgeons wearing white coats and formal attire, which
      improves credibility of these professionals to correctly solve medical
      situations.

PMID- 29189857
TI  - [Risk factors associated with hypertension. Analysis of the 2009-2010 Chilean
      health survey].
AB  - BACKGROUND: High blood pressure is one of the major risk factors for the
      development of cardiovascular disease, affecting 27% of the Chilean population in
      2010. AIM: To determine the risk factors associated with the development of
      hypertension. MATERIAL AND METHODS: Analysis of the database of the 2009-2010
      National Health Survey in which 4,901 participants were included. Socio
      demographic factors, physical activity, eating habits, well-being and
      comorbidities were analyzed. RESULTS: Women had a lower risk of developing
      hypertension than men (Odds ratio (OR): 0.69, 95% confidence intervals (CI): 0.59
      0.81, p < 0.01). In both men and women, the risk is greater over the age of 25
      years (OR: 2.90, 95% CI: 1.55-5.43, p < 0.01). The risk is greater in subjects
      who were overweight (OR: 1.61, 95% CI: 1.31-1.98, p < 0.01), obese (OR: 3.18, 95%
      CI: 2.56-3.95, p < 0.01), or had central obesity (OR: 2.25, 95% CI: 1.85-2.72, p
      < 0.01). Subjects with a family history of hypertension and diabetes also have a
      higher risk. CONCLUSIONS: Identifying the risk factors associated with
      hypertension allows public health policies to be tailored to its prevention.

PMID- 29189858
TI  - [Psychometric properties of a spanish version of the Beck depression inventory
      IA].
AB  - BACKGROUND: According to the Chilean National Health Survey (2009-2010), 17% of
      people aged 15 years or more have depressive symptoms. Thus, freely-available,
      easily-administered, and highly sensitive screening tests for depression are
      needed in clinical and research settings. AIM: To evaluate the psychometric
      properties of a Spanish version of the Beck Depression Inventory (BDI-IA) in
      adult Chilean population. MATERIAL AND METHODS: The inventory was applied to a
      sample of 1.105 adults aged between 18 to 73 years (94% women). Ninety nine
      participants were outpatients receiving treatment for affective disorders, 932
      were parents and/or guardians of students enrolled in schools and 73 were
      university students (sample with no known depressive disorder). To perform data
      analysis, two groups from the random combination of both samples were generated.
      RESULTS: The inventory showed an appropriate degree of internal consistency
      (Cronbach alpha = .92). An exploratory factor analysis suggested a one-factor
      solution. This solution was reinforced with a confirmatory factor analysis, which
      displayed an adequate goodness of fit. The cutoff score, based on the Youden
      Index, was 13/14 points. It was able to discriminate between depressed and non
      depressed participants. CONCLUSIONS: These results indicate that the BDI-IA is an
      appropriate instrument to assess depressive symptoms in Chilean adults.

PMID- 29189859
TI  - [Is abortion a serious public health problem in Chile in the field of maternal
      perinatal health?]
AB  - BACKGROUND: The World Health Organization, by 2014, estimates that approximately
      22 million unsafe abortions take place every year in the world, almost all of
      them in developing countries. The Millennium Goals, as part of the fifth
      compendium, focused on maternal health by proposing that member states should
      reduce maternal mortality to 75% by 2015. AIM: To determine, using maternal
      health indicators, if abortion in Chile is a priority health problem. MATERIAL
      AND METHODS: Data about maternal mortality and its causes between 1982 and 2014,
      was obtained from the databases available at the Chilean Ministry of Health.
      Trend analyzes were carried out using linear autoregressive models. RESULTS:
      Between 1982 and 2012, maternal mortality rates decreased from 51.8 to 18.3 per
      100,000 live births. Complications of pregnancy, childbirth and puerperium were
      the first three causes and the last one is abortion. The proportion of abortions
      due to unspecified causes, including induced abortion, decreased from 36.6% to
      26.1% between 2001 and 2012. CONCLUSIONS: Abortion is not a public health problem
      in Chile. To continue reducing maternal mortality, programs for the early
      detection of risks such as diabetes, obesity and hypertension should be
      implemented.

PMID- 29189860
TI  - [False negative spect parathyroid scintigraphy with sestamibi in patients with
      primary hyperparathyroidism].
AB  - BACKGROUND: 99mTc-sestamibi parathyroid SPECT scintigraphy is a useful tool in
      the pre-operative study of hyperparathyroidism. False negatives (FN) have been
      reported in 5.7-14% of the examinations. AIM: To characterize 99mTc-sestamibi FN
      in cases referred for primary hyperparathyroidism (PHP) to a university hospital.
      MATERIAL AND METHODS: Descriptive retrospective analysis. We included patients
      with PHP, studied with SPECT scintigraphy, operated at our center between 2008
      and 2015. Clinical and surgical data were recorded; biopsies of the FN were
      blindly reviewed by one pathologist. RESULTS: One hundred twenty one
      scintigraphies fulfilled the inclusion criteria. Seven (5.8%) were negative and
      114 positive. There was no difference in age, sex and PTH levels between FN and
      true positive scintigraphies. At surgery, one FN case had two hyperplasic glands
      and two cases had ectopic glands. Pathology reported adenoma in three cases,
      hyperplasia in three and carcinoma in one. The largest diameter of the lesion was
      lower in FN (1.3 and 2.1 cm respectively, p = 0.02) and the proportion of
      adenomas was higher in true positive cases (29% and 75% respectively; p < 0.01).
      The interval between scintigraphy and parathyroidectomy was greater in FN with a
      median of 92 days (range 20 days-3.2 years, p < 0.01). The percentage of
      oxyphilic cells observed was similar in both groups. CONCLUSIONS: FN parathyroid
      SPECT scintigraphies in PHP are uncommon. They corresponded to lesions under the
      equipment's resolution limit and resulted in longer time lags between
      scintigraphy and surgery.

PMID- 29189861
TI  - [Study and management of thyroid nodes by non specialist physicians: SOCHED
      consensus].
AB  - The thyroid nodule is a frequent cause of primary care consultation. The
      prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to
      67% by the incidental detection of nodules on ultrasound. The vast majority are
      benign and asymptomatic, staying stable over time. The clinical importance of
      studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10%
      of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and
      Diabetes) asked the Thyroid Study Group to develop a consensus regarding the
      diagnostic management of the thyroid nodule in Chile, aimed at non-specialist
      physicians and adapted to the national reality. To this end, a multidisciplinary
      group of 31 experts was established among university academics, active
      researchers with publications on the subject and prominent members of scientific
      societies of endocrinology, head and neck surgery, pathology and radiology. A
      total of 14 questions were developed with key aspects for the diagnosis and
      subsequent referral of patients with thyroid nodules, which were addressed by the
      participants. In those areas where the evidence was insufficient or the national
      reality had to be considered, the consensus opinion of the experts was used
      through the Delphi methodology. The consensus was approved by the SOCHED board
      for publication.

PMID- 29189862
TI  - [Management of facial injuries in the emergency room].
AB  - Facial injuries are cause of consultation in emergency departments. The
      maxillofacial region contains several structures that are vital for life. Hence,
      an early assessment and management of facial injuries is important to avoid their
      consequential complications and eventual mortality. This article is a review of
      the literature about the emergency clinical assessment and management of
      traumatic facial injuries by non-specialists.

PMID- 29189863
TI  - [The association of schizophrenia with chronic non transmissible diseases].
AB  - The life expectancy of patients with schizophrenia (SCH) is 11 to 20 years less
      than the general population. There is an association between SCH and various
      diseases and chronic conditions, highlighting the cardio-metabolic diseases. This
      association has been attributed to the use of antipsychotics, however, evidence
      has also shown intrinsic susceptibility of schizophrenic patients the development
      of chronic conditions. This review aims to update knowledge about chronic
      conditions such as cardiometabolic risk and sleep, bone and kidney disorders
      related to SCH. These patients have a high prevalence of risk behaviors,
      including smoking and poor diet. They have a worse metabolic profile than the
      general population and a greater likelihood of developing metabolic syndrome,
      diabetes and cardiovascular disease. SCH has also been associated with other
      chronic diseases such as osteoporosis and chronic kidney disease. The high
      prevalence of these comorbidities in schizophrenic population is not explained
      solely by the antipsychotic treatment, therefore intrinsic mechanisms associated
      to SCH are postulated to be associated with these conditions. This new
      information requires a change in the multidisciplinary medical approach for the
      study and management of schizophrenic patients.

PMID- 29189864
TI  - [The potential contribution of adenovirus 36 to the development of obesity].
AB  - The evidence of the last 20 years shows a link between viral infections and
      obesity in animals and humans. There are five adenovirus which have been
      associated with development of obesity in animals. SMAM-1 virus was the first
      studied in humans associated with obesity. There is compelling evidence that Ad
      36 virus could contribute to the development of obesity in humans and it is
      related with body mass index (BMI). This manuscript reviews the association
      between Ad-36 and the other four virus infections with obesity. An electronic
      search of articles in the databases PubMed and Scielo, with use of key words:
      obesity, infection, adipose tissue, Ad-36, 3T3-L1 was performed. The search was
      restricted "human" and "animals". The importance of the relationship between
      virus infections and obesity has increased over the past two decades. Ad-36 shows
      more compelling evidence in humans. There are reports involving this virus in the
      enhancement of adipogenesis, adipocyte differentiation, a lower secretion of
      leptin and an increased insulin sensitivity. Future work should focus in larger
      cohort studies to confirm this association, which explains the global obesity
      epidemic from a new perspective.

PMID- 29189865
TI  - [The fight against malnutrition of the medical community between 1860 and 1940].
AB  - The aim of this manuscript is to highlight the contribution of the first two
      generations of physicians who faced malnutrition in Chile, between the end of
      nineteenth century and the first decades of the twentieth century. In the history
      of Chilean medicine, there is a paucity of research about the role of these
      physicians in the fight against malnutrition. The main interest was centered in
      the forties of the twentieth century and the first policies and actions for the
      working class feeding have been overlooked. The existence of two pioneering
      groups that have common elements and differences to face the problem of under
      nutrition is established.

PMID- 29189866
TI  - [Role of surgery in Saprochaete capitata (S. capitata) sepsis in a patient with
      acute myeloid leukemia].
AB  - Saprochaete capitata (S. capitata) fungal sepsis is a severe condition with a
      clinical presentation that is similar to other yeast originated fungal sepsis. It
      is observed in patients with hematological malignancies such as acute myeloid
      leukemia and neutropenia. We report a 23 year old male presenting with cough,
      fever and malaise. A bone marrow biopsy led to the diagnosis of acute myeloid
      leukemia. During the first cycle of chemotherapy the patient presented fever:
      blood cultures were positive for Klebsiella pneumoniae. Despite antimicrobial
      treatment, fever persisted; a computed tomography showed a focal splenic lesion;
      a left exudative pleural effusion appeared. A Matrix Assisted Laser Desorption
      Ionization-Time of Flight mass spectrometry identified the presence of S.
      capitata. After multiple antifungal treatments and pleural cavity cleansing by
      means of videothoracoscopy and laparoscopic splenectomy, the infection resolved
      and the patient completed his chemotherapy.

PMID- 29189867
TI  - [Metformin-associated lactic acidosis. Report of one case].
AB  - Metformin-associated lactic acidosis is a severe and infrequent adverse event.
      Early diagnosis is essential to start an early treatment, which often has
      favorable results. We report a 56 years old non-insulin-requiring type 2 diabetic
      female who developed a severe metabolic acidosis associated with metformin in
      relation to an acute renal failure secondary to infectious diarrhea. Early
      treatment with bicarbonate and continuous hemofiltration allowed a quick
      improvement of the patient. Metformin-associated lactic acidosis has an elevated
      mortality (50-80%) and has a specific and effective treatment. Therefore, the
      condition must be born in mind.

PMID- 29189868
TI  - [Breast osteosarcoma originating in a phyllodes tumor. Report of one case].
AB  - Phyllodes tumors account for less than 1% of tumors of the mammary gland, have
      both epithelial and stromal components and are classified as benign, borderline
      and malignant. The malignant tumors are highly heterogeneous: they can
      differentiate to liposarcomas, fibrosarcomas, rhabdomyosarcomas, chondrosarcomas
      or osteosarcomas. The differentiation to osteosarcoma is extremely rare,
      constitutes 1.3% of cases and is very aggressive. The standard treatment of these
      tumors is surgical. The role of radiotherapy and chemotherapy is not clear.
      However, in patients in whom wide surgical margins are not achieved, adjuvant
      radiotherapy can be of help. We report a 63 years old female with a right breast
      osteosarcoma with an osteoclastic component, originating in a phyllodes tumor.
      The tumor was excised surgically and afterwards she was treated with 10 sessions
      of 50 Gy of radiotherapy in 25 fractions. She has remained free of disease for
      the last 10 months.

PMID- 29189869
TI  - [Acute severe ulcerative colitis treated with accelerated infliximab induction.
      Case report].
AB  - Acute severe ulcerative colitis (ASUC) is a potentially life-threatening
      condition that requires early recognition, hospitalization and adequate
      treatment. Currently, the use of infliximab in ulcerative colitis (UC) is
      recommended in the case of severe disease refractory to corticosteroids, once
      that superimposed bacterial or viral infections (such as cytomegalovirus or
      Clostridium difficile) have been excluded. However, conventional weight-based
      regimens of infliximab might be insufficient for patients with ASUC. Accelerated
      infliximab induction regimen may increase its serum concentration levels and
      efficacy by reducing early colectomy rates in these patients. We report a 34 year
      old female presenting with an ASUC. She was initially treated with hydrocortisone
      300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response.
      At the fifth day of therapy, an accelerated induction therapy with infliximab was
      started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there
      was a favorable response with reduction of abdominal pain, stool frequency and
      hematochezia. She was discharged with prednisone and azathioprine. After a year
      of starting infliximab, the patient remains in clinical remission.

PMID- 29189870
TI  - [Considerations about decreasing body fat with high intensity intermittent
      training and nutrition counseling].

PMID- 29189871
TI  - [The economic burden of physical inactivity in Chile].

PMID- 29189873
TI  - [Diagnostic workup of urethral strictures].
AB  - Urethral stricture is a narrowing of the urethra due to scar tissue. It causes
      obstructive voiding dysfunction and can lead to long-term damage of the entire
      urinary tract. The probability of therapeutic success is dampened by a high rate
      of recurrence. Therefore, a careful taking of the patient's history and further
      diagnostics are crucial for finding the appropriate form of therapy. This review
      highlights the clinical presentation and diagnostic workup of urethral
      strictures.

PMID- 29189872
TI  - [How frequently are depressive disorders recognized in primary care patients? : A
      cross-sectional epidemiological study in Germany].
AB  - BACKGROUND: Primary care physicians (PCPs) play a crucial role for guideline
      oriented intervention in patients with depression. OBJECTIVES: Based on a
      diagnostic screening questionnaire, this study investigates the sensitivity of
      PCPs to recognize patients with depression as well as the factors facilitating
      recognition and concordant diagnostic decisions. METHOD: In a cross-sectional
      epidemiological study in six regions of Germany, 3563 unselected patients filled
      in questionnaires on mental and physical complaints and were diagnostically
      evaluated by their PCP (N = 253). The patient reports on an established
      Depression-Screening-Questionnaire (DSQ), which allows the approximate derivation
      of an ICD-10 depression diagnosis, were compared with the physician diagnosis (N
      = 3211). In a subsample of discordant cases a comprehensive standardized clinical
      diagnostic interview (DIA-X/CIDI) was applied. RESULTS: On the study day, the
      prevalence of ICD-10 depression was 14.3% according to the DSQ and 10.7%
      according to the physician diagnosis. Half of the patients identified by DSQ were
      diagnosed with depression by their physician and two thirds were recognized as
      mental disorder cases. More severe depression symptomatology and the persistent
      presence of main depression symptoms were related to better recognition and
      concordant diagnostic decisions. Diagnostic validation interviews confirmed the
      DSQ diagnosis in the majority of the false-negative cases. Indications for at
      least a previous history of depression were found in up to 70% of false-positive
      cases. CONCLUSION: Given the high prevalence of depression in primary care
      patients, there is continued need to improve the recognition and diagnosis of
      these patients to assure guideline-oriented treatment.

PMID- 29189874
TI  - Correction to: Incorporating pleiotropic quantitative trait loci in dissection of
      complex traits: seed yield in rapeseed as an example.
AB  - The article "Incorporating pleiotropic quantitative trait loci in dissection of
      complex traits: seed yield in rapeseed as an example", written by J. Zou et al,
      was originally published Online First without open access.

PMID- 29189875
TI  - Cardiac intensive care unit organisation in an economically less developed
      European country.

PMID- 29189876
TI  - Is ticagrelor safe in intensive care unit patients? Focus on bradycardic events.

PMID- 29189877
TI  - [Surgical strategies for carcinoma of the cardia (AEG type II)].

PMID- 29189879
TI  - [Vascular anomalies. Part I: vascular tumors].
AB  - Vascular anomalies represent a spectrum of structural disorders and inborn errors
      of vascular morphogenesis, which may affect the entire arterial and venous
      vascular tree. They are divided into two major categories: tumors, which exhibit
      endothelial hyperplasia and malformations, which have normal endothelial turnover
      unless disturbed. Depending on their nature and complexity they can range from a
      simple "birthmark" to life-threatening entities. The relatively low incidence (4
      10%) of vascular anomalies among the general population combined with the fact
      that their management often falls within the purview of several different medical
      and surgical specialties, has traditionally resulted in insufficient expertise in
      the management of these conditions. Therefore, accurate identification, a uniform
      nomenclature and a multidisciplinary approach are paramount for correct
      management.

PMID- 29189878
TI  - [Quality indicators for colon cancer surgery : Evidence-based development of a
      set of indicators for the outcome quality].
AB  - BACKGROUND: Quality assessment in surgery is gaining in importance. Although
      sporadic recommendations for quality indicators (QI) in oncological colon surgery
      can be found in the literature, these are usually not systematically derived from
      a solid evidence base. Moreover, reference ranges for QI are unknown. OBJECTIVE:
      The aim of this initiative was the development of evidence-based QI for
      oncological colon resections by an expert panel invited by the German Society of
      General and Visceral Surgery (DGAV). Reference ranges from the literature and
      reference values from the Study, Documentation, and Quality Center (StuDoQ)|Colon
      Cancer Register were compared in order to deduce recommendations which are
      tailored to the German healthcare system. RESULTS: Based on the most recent
      scientific evidence and agreed by expert consensus, five QI for oncological colon
      surgery were defined and evaluated according to the QUALIFY tool. Mortality,
      MTL30 (mortality, transfer to another acute care hospital, or length of stay >=30
      days), anastomotic leakage requiring reintervention, surgical site infections
      necessitating reopening of the wound and >=12 lymph nodes in the specimen
      qualified as QI owing to their relevance, scientific nature, and practicability.
      Based on the results of the systematic literature search and the statistical
      analysis of the StuDoQ|Colon Cancer Register, preliminary reference values are
      proposed for each QI. CONCLUSION: The presented set of QI seems appropriate for
      quality assessment of oncological colon surgery in the context of the German
      healthcare system. The validity of the QI and the reference values must be
      reviewed within the framework of their implementation. The StuDoQ|Colon Cancer
      Register provides a suitable infrastructure for collecting clinical data for
      quality assessment and risk adjustment.

PMID- 29189880
TI  - [Sexual health in flux].

PMID- 29189881
TI  - Satisfactory functional and radiological outcomes can be expected in young
      patients under 45 years old after open wedge high tibial osteotomy in a long-term
      follow-up.
AB  - PURPOSE: To report the long-term outcomes of medial open wedge high tibial
      osteotomy (MOWHTO) for the treatment of medial compartment knee osteoarthritis in
      patients younger than 45 years old. It was hypothesized that the correction of
      knee alignment would result in preservation of knee function in a long-term
      follow-up. METHODS: Patients under 45 years old, who underwent MOWHTO for
      symptomatic medial compartment knee osteoarthritis between 2001 and 2005 were
      retrospectively reviewed after a minimum of 10 years. The osteotomy was performed
      utilizing a locking plate without the use of bone graft. Patients were evaluated
      pre- and postoperatively using the International Knee Documentation Committee
      Score, the Oxford Knee Score, the Knee injury Osteoarthritis Outcome Score and
      the Short Form-12 Score. Standardized standing whole-limb radiographs were also
      obtained to assess mechanical tibiofemoral angle (mTFA) and the grade of
      osteoarthritis. RESULTS: A total of 20 patients (18 males, 2 females, mean age
      35.4 years) with a mean follow-up of 12.3 years were included in the study.
      During the follow-up period, one patient required conversion to total knee
      replacement (95% survival rate). All clinical outcome scores (IKDC, KOOS, OKS,
      and SF-12) significantly improved postoperatively (p < 0.05), with no significant
      deterioration over time. Preoperative varus alignment with an mTFA of - 5.8 +/-
      2.4 degrees  was corrected to 2.5 +/- 1.9 degrees  immediately after surgery (p <
      0.05), and remained 2.2 +/- 1.7 degrees  at the last follow-up. Furthermore, no
      significant radiographic progression of osteoarthritis was observed. CONCLUSIONS:
      MWOHTO with a locking plate is an effective joint preservation method to treat
      medial compartment OA in active patients less than 45 years. Clinical and
      radiological results are satisfactory and the survival rate is 95%, 12 years
      after the procedure. LEVEL OF EVIDENCE: Level IV therapeutic, retrospective,
      cohort study.

PMID- 29189882
TI  - The transportal technique shows better clinical results than the transtibial
      techniques for single-bundle anterior cruciate ligament reconstruction.
AB  - PURPOSE: Although anatomical and independent drilling techniques, such as
      transportal (TP) technique, have become more popular in anterior cruciate
      ligament (ACL) reconstruction, the TP technique has not been shown to yield
      superior clinical or functional outcomes compared to the transtibial (TT)
      technique. The aim of the current meta-analysis was to compare clinical outcomes
      of the TP and TT techniques, as determined by patient-reported outcome scores and
      knee joint laxity tests. It was hypothesized that the TP and TT techniques of ACL
      reconstruction would yield similar patient-reported functional outcomes and
      similar results on knee joint laxity tests. METHODS: Studies were included if
      they reported at least one of the following clinical outcomes: IKDC score, IKDC
      examination, Lysholm knee score, and Tegner activity score. Knee stability was
      evaluated by single or multiple parameters of the following knee laxity
      examinations: the Lachman test, the pivot shift test, and side-to-side difference
      on the instrumented knee laxity test. RESULTS: Sixteen studies were finally
      included in this meta-analysis. The proportions of patients with normal grade on
      the IKDC examination [odds ratio (OR) 2.23; 95% confidence interval (CI) 1.41
      3.53; P = 0.0006] and Lysholm score (mean difference 1.27; 95% CI 0.23-2.31; P =
      0.02) after surgery were higher with the TP than with the TT technique, but there
      were no differences in IKDC and Tegner scores. The postoperative proportion of
      normal knee joint stability was significantly higher with the TP than the TT
      technique, on both Lachman (OR 2.29; 95% CI 1.35-3.92; P = 0.002) and pivot shift
      (OR 2.13; 95% CI 1.12-4.05; P = 0.02) tests. The pooled mean side-to-side
      difference was 0.73 mm lower with the TP than the TT technique (95% CI - 1.14 to 
      0.32 mm; P = 0.0005). CONCLUSION: This meta-analysis showed that the clinical
      outcomes of ACL reconstruction were better with the TP than the TT technique,
      both on knee functional outcome scales and knee laxity tests. The findings thus
      suggest that the TP technique would be a better option for single-bundle ACL
      reconstruction compared to the TT technique. LEVEL OF EVIDENCE: III.

PMID- 29189883
TI  - Arthroscopic treatment combined with the ankle stabilization procedure is
      effective for sinus tarsi syndrome in patients with chronic ankle instability.
AB  - PURPOSE: This study aimed to investigate the results of arthroscopic treatment
      combined with ankle stabilization procedure for sinus tarsi syndrome (STS) in
      patients with chronic ankle instability (CAI). METHODS: A total of 57 patients
      (31 males and 26 females, average age 29.9 +/- 8.4 years ranging from 15 to 52
      years) with STS and CAI who accepted operation from 2013 to 2015 were included in
      this retrospective study. Surgical procedures included thorough tarsal sinus
      debridement and repair or reconstruction of lateral ankle ligaments according to
      the quality of ligaments. American Orthopedic Foot and Ankle Society (AOFAS)
      score, Karlsson score, and Tegner score were evaluated preoperatively and at
      final follow-up. RESULTS: All the patients accepted thorough debridement of
      tarsal sinus. Of these, 53 patients (93.0%) had an arch structure between the
      posterior subtalar joint and the middle subtalar joint. Further, 54 patients
      accepted lateral ankle ligament repair, and 3 patients accepted ligament
      reconstruction. A total of 40 patients were followed up with an average time of
      30.7 months. The modified AOFAS score increased from 62.5 (27-90) to 93 (67-100),
      the Karlsson score increased from 57 (30-82) to 90 (55-100), and the Tegner score
      increased from 1 (1-3) to 5 (1-8). CONCLUSIONS: Arthroscopic treatment combined
      with the ankle stabilization procedure could get satisfactory results for STS in
      patients with CAI. The arch structure composed by medial calcaneal component of
      the medial root of the inferior extensor retinaculum (MCC) might contribute to
      the pathological mechanism of STS. LEVEL OF EVIDENCE: IV.

PMID- 29189884
TI  - Adaptive Immune Cell Dysregulation and Role in Acute Pancreatitis Disease
      Progression and Treatment.
AB  - Acute pancreatitis (AP) is an inflammation of the pancreas caused by various
      stimuli including excessive alcohol consumption, gallstone disease and certain
      viral infections. Managing specifically the severe form of AP is limited due to
      lack of an understanding of the complex immune events that occur during AP
      involving immune cells and inflammatory molecules such as cytokines. The relative
      abundance of various immune cells resulting from the immune dysregulation drives
      disease progression. In this review, we examine the literature on the adaptive
      immune cells in AP, the prognostic value of these cells in stratifying patients
      into appropriate care and treatment strategies based on cell frequency in
      different AP severities are discussed.

PMID- 29189885
TI  - Invited review: the tale of ECIRS (Endoscopic Combined IntraRenal Surgery) in the
      Galdakao-modified supine Valdivia position.
AB  - Modern-day percutaneous nephrolithotomy (PNL) has undergone considerable
      evolution, mainly driven by the improvement in access techniques, endoscopic
      instrumentation technology, lithotripsy devices and drainage management. The
      introduction of the supine and supine-modified positions is also part of this
      evolution, enabling comfortable and safe procedures from an anaesthesiological
      point of view, and an easy combined retrograde surgery [Endoscopic Combined
      IntraRenal Surgery (ECIRS)], allowing tailoring of the procedure on the patient,
      the dynamic anatomy of the collecting system and the urolithiasis. The conceptual
      value of ECIRS extends beyond the single diagnostic and active advantages due to
      the simultaneous contribution of the flexible retrograde ureteroscopy: the merit
      consists in the promotion of the versatile attitude of the urologist, and in the
      fulfillment of a personalized stone management. ECIRS has no pretensions of
      superiority, but for sure is a new safe and effective way of interpreting PNL, in
      the hands of an experienced surgical team.

PMID- 29189886
TI  - Antiurolithiatic effect of the taraxasterol on ethylene glycol induced kidney
      calculi in male rats.
AB  - Taraxasterol is one of the important constituents of Taraxacum officinale L.
      (Compositae) with antioxidant potential. The present study was designed to
      evaluate and compare the antiurolithiatic effects of taraxasterol and potassium
      citrate in the ethylene glycol induced urolithiatic rat. Urolithiasis was induced
      by ammonium chloride and ethylene glycol in adult male rats. Taraxasterol (2, 4
      and 8 mg/kg) and potassium citrate (2.5 g/kg) were treated for 33 days by gavage.
      Then, the animals were anesthetized and weighted and blood, urine, liver and
      kidney sampling were done. The kidney sections were prepared by hematoxylin &
      eosin staining. The liver and kidney coefficients, urine pH, calcium, magnesium,
      oxalate and citrate levels, serum albumin, calcium and magnesium levels, serum
      alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase
      activities, superoxide dismutase and glutathione peroxidase activities in serum,
      kidney and liver, number of calcium oxalate crystal deposits, score of crystal
      deposits, score of histopathological damages and score of inflammation in kidney
      sections were evaluated. The results showed that taraxasterol decreased liver and
      kidney coefficients (p < 0.001), serum calcium (p < 0.01) level, serum alanine
      aminotransferase (p < 0.001), aspartate aminotransferase (p < 0.001), lactate
      dehydrogenase (p < 0.05) activities, urine magnesium (p < 0.05) and oxalate (p <
      0.001) levels, number of crystal deposits (p < 0.001), score of crystal deposits
      (p < 0.01), score of histopathological damages (p < 0.001) and score of
      inflammation (p < 0.01) in kidney sections, while increased urine pH (p < 0.01),
      calcium (p < 0.001) and citrate (p < 0.05), serum magnesium (p < 0.001) and
      albumin (p < 0.01) levels, superoxide dismutase and glutathione peroxidase in
      serum (p < 0.01), kidney (p < 0.05 and p < 0.001, respectively) and liver (p <
      0.01 and p < 0.001, respectively) tissue homogenates in treated urolithiatic rats
      in comparison to the control urolithiatic rats. The effect of potassium citrate
      is the same as taraxasterol in treated urolithiatic rats. In conclusion, the
      effect of taraxasterol could be by improving liver function, changing serum and
      urine parameters, maintaining the antioxidant environment, reducing crystal
      deposition, excretion of small deposits from kidney and reducing the chance of
      them being retained in the urinary tract.

PMID- 29189887
TI  - Eosinophilic granulomatosis with polyangiitis without respiratory symptoms or
      asthma in an adolescent: case report and literature review.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss
      syndrome, is a systemic necrotizing vasculitis of the small and medium vessels.
      It is primarily associated with respiratory conditions such as asthma and
      sinusitis as well as eosinophilia, neuropathy, pulmonary infiltrates, and
      vasculitis. EGPA is extremely rare in the pediatric age group, and respiratory
      system disorders are usually predominant in EGPA patients. A 14-year-old boy
      presented with rash and severe extremity pain. He had eosinophilia, and
      electroneuromyography demonstrated sensorimotor polyneuropathy. His skin biopsy
      revealed necrotizing eosinophilic vasculitis and eosinophilic panniculitis.
      Although he had no respiratory symptoms or history of asthma, prominent pulmonary
      involvement was evident on thoracic MRI. After treatment, his complaints of pain
      improved but mild neuropathy persisted. After 4 years of follow-up, he had
      minimal hypoesthesia in his right hand but had not experienced any relapses. This
      case highlights the fact that in cases suspected of EGPA, even without
      respiratory symptoms or asthma, detailed imaging should be performed for a
      definitive diagnosis. In addition, mild neurological findings may persist despite
      treatment in EGPA. The relevant literature on EGPA, with specific reference to
      pediatric cases, is reviewed.

PMID- 29189888
TI  - On the Early Evolution of Catabolic Pathways: A Comparative Genomics Approach. I.
      The Cases of Glucose, Ribose, and the Nucleobases Catabolic Routes.
AB  - Compared with the large corpus of published work devoted to the study of the
      origin and early development of anabolism, little attention has been given to the
      discussion of the early evolution of catabolism in spite of its significance. In
      the present study, we have used comparative genomics to explore the evolution and
      phylogenetic distribution of the enzymes that catalyze the extant catabolic
      pathways of the monosaccharides glucose and ribose, as well as those of the
      nucleobases adenine, guanine, cytosine, uracil, and thymine. Based on the oxygen
      dependence of the enzymes, their conservation, and evolution, we speculate on the
      relative antiquity of the pathways. Our results allow us to suggest which
      catabolic pathways and enzymes may have already been present in the last common
      ancestor. We conclude that the enzymatic degradations of ribose, as well as those
      of purines adenine and guanine, are among the most ancient catabolic pathways
      which can be traced by protein-based methodologies.

PMID- 29189889
TI  - Is Cr(III) toxic to bacteria: toxicity studies using Bacillus subtilis and
      Escherichia coli as model organism.
AB  - The objective of this work is to detect the mode of damage caused by Cr(III), one
      of the widely used industrial pollutant on Bacillus subtilis-industrial strain
      168 and Escherichia coli MTCC 40. Bioassays are very sensitive, precise,
      economical and rapid for detecting early stages of pollution. The detrimental
      effect of trivalent chromium becomes clear from the growth profile and growth
      inhibition studies. Mode of action of damage by trivalent chromium in bacterial
      model was found to be oxidative, as chromium is one of the redox active metals.
      The generation of reactive oxygen species (ROS) resulted in membrane damage which
      in turn had a detrimental effect on the membrane proteins as well as the DNA. The
      structural changes in the SEM and AFM images clearly reveals the damage caused by
      Cr(III) to the test bacterial models. Trivalent chromium causes greater DNA,
      protein and membrane damage in case of E. coli than B. subtilis. Membrane damage
      caused by ROS becomes evident from the production of Thiobarbituric acid reactive
      substances (TBARs) as the mechanism of killing followed by DNA damage and the
      production of elevated levels of stress proteins known as extracellular cellular
      proteins.

PMID- 29189890
TI  - Decoding the role of hypothetical protein All3255 of Anabaena PCC7120 in heavy
      metal stress management in Escherichia coli.
AB  - Cadmium is a non-essential toxic heavy metal for organisms, including plants and
      cyanobacteria. Cadmium resistance transporters involved in resistance of cells
      against various toxicants such as drugs and effluxes cytotoxic compounds from
      cells. However, cadmium resistance-associated protein (CadD) has never been
      reported from a diazotrophic cyanobacterium Anabaena sp. To test whether the
      hypothetical protein All3255 of Anabaena sp. PCC7120 a homolog of cadmium
      resistance-associated protein (CadD) involved in cadmium or heavy metal
      resistance or not, cloning and heterologous expression analysis of all3255
      performed in Escherichia coli BL21 (DE3). Our results revealed that the strain
      transformed with pGEX-5X-2 + all3255 showed resistant towards not only to cadmium
      but also other heavy metals such as nickel, copper, zinc, lead and cobalt in
      addition to arsenic than those of transformed with empty vector (pGEX-5X-2).
      Furthermore, the results of metal accumulation analysis of these cells unveil a
      lower accumulation of tested heavy metals in all3255-overexpressing E. coli cells
      than those transformed with empty vector. This study strongly supports the role
      of All3255 of Anabaena sp. PCC7120 as a CadD efflux pump of heavy metals in
      E.coli.

PMID- 29189892
TI  - Maternal serum homocysteine and uterine artery Doppler as predictors of
      preeclampsia and poor placentation.

PMID- 29189891
TI  - Coralloluteibacterium stylophorae gen. nov., sp. nov., a new member of the family
      Lysobacteraceae isolated from the reef-building coral Stylophora sp.
AB  - A bacterial strain, designated Sty a-1T, was isolated from a reef-building coral
      Stylophora sp., collected off coast of Southern Taiwan and characterized using
      the polyphasic taxonomy approach. Cells of strain Sty a-1T were Gram-staining
      negative, aerobic, poly-beta-hydroxybutyrate accumulating, motile by means of
      flagella, non-spore forming, straight rod-shaped and colonies were yellow and
      circular. Growth occurred at 15-40  degrees C (optimum, 30-35  degrees C), at pH
      6-10 (optimum, pH 6.5-8) and with 0-7% NaCl (optimum, 2-3%). The predominant
      fatty acids were iso-C15:0, iso-C17:1 omega9c, summed feature 3 (comprising C16:1
      omega7c and/or C16:1 omega6c) and iso-C17:0. The major isoprenoid quinone was Q-8
      and the DNA G+C content was 68.5 mol%. The polar lipid profile consisted of a
      mixture of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine,
      diphosphatidylglycerol, an uncharacterized aminophospholipid and three
      uncharacterized lipids. The major polyamines were spermidine, putrescine and
      homospermidine. Phylogenetic analyses based on 16S rRNA and four housekeeping
      gene sequences (recA, atpD, rpoA and rpoB) showed that strain Sty a-1T forms a
      distinct lineage with respect to closely related genera in the family
      Lysobacteraceae, most closely related to Lysobacter, Silanimonas, Arenimonas and
      Luteimonas and the levels of 16S rRNA gene sequence similarity with respect to
      the type species of related genera are less than 95%. On the basis of the
      genotypic and phenotypic data, strain Sty a-1T represents a novel genus and
      species of the family Lysobacteraceae, for which the name Coralloluteibacterium
      stylophorae gen. nov., sp. nov. is proposed. The type strain is Sty a-1T (= BCRC
      80968T = LMG 29479T = KCTC 52167T).

PMID- 29189893
TI  - Maternal hemodynamics in late gestation and immediate postpartum in singletons
      vs. twin pregnancies.
AB  - PURPOSE: Differences in hemodynamic changes during a cesarean section (CS)
      between twin and singleton pregnancies are poorly defined. The Non-Invasive
      Cardiac System (NICaS) is an impedance device that measures cardiac output (CO)
      and its derivatives. We compared maternal cardiac parameters using NICaSTM in
      singleton and twins before and during delivery, as well at the early puerperium
      in healthy women undergoing CS at term. METHODS: This prospective longitudinal
      study included women with twin (n = 27) or singleton pregnancies (n = 62) whose
      hemodynamic parameters were assessed by NICaS before an elective CS, after spinal
      anesthesia, immediately after delivery, after fascia closure, and within 24-36
      and 48-72 h postpartum. RESULTS: By 24-36 h postpartum, the mean arterial
      pressure and the total peripheral resistance equaled preoperative values in both
      groups. The CO increased throughout the CS and peaked immediately after delivery
      in the singleton group (P < 0.0001), after which it abruptly began to decline
      until reaching a nadir 24-36 h after delivery (P < 0.0001), while it remained
      steady throughout the CS and then dropped until 24-36 h after delivery in the
      twin group (P < 0.05). None of the studied parameters differed significantly
      between the groups for the 24-36 and 48-72 h postpartum measurements.
      CONCLUSIONS: Hemodynamic parameters immediately before, during and shortly after
      CS in singleton and twin pregnancies are equivalent. Further evaluations of the
      value of NICaSTM in assessing cardiovascular-related pregnancy complications are
      warranted.

PMID- 29189895
TI  - Acceptance and barriers to access of occupational e-mental health: cross
      sectional findings from a health-risk population of employees.
AB  - PURPOSE: Occupational e-mental-health (OEMH) may extend existing instruments for
      preservation or restoration of health and work ability. As a key precondition to
      efficient implementation, this study examined acceptance and person-centered
      barriers to potential uptake of OEMH for work-related distress in employees with
      an elevated risk of early retirement. METHODS: Within the framework of the "Third
      German Sociomedical Panel of Employees", 1829 employees with prior sickness
      absence payments filled out a self-administered questionnaire. Participants had a
      mean age of 49.93 years (SD = 4.06). 6.2% indicated prior use of eHealth
      interventions. Potential predictors of acceptance of OEMH were examined based on
      the "Unified Theory of Acceptance and Use of Technology" (UTAUT) extended by work
      ability, mental health, eHealth literacy and demographic characteristics.
      RESULTS: 89.1% (n = 1579) showed low to moderate acceptance (M = 2.20, SD = 1.05,
      range 1-5). A path analysis revealed significant, positive direct effects of
      UTAUT predictors on acceptance (performance expectancy: 0.48, SE = 0.02, p <
      0.001; effort expectancy: 0.20, SE = 0.02, p < 0.001; social influence: 0.28, SE
      = 0.02, p < 0.001).Online time and frequency of online health information search
      were further positive direct predictors of acceptance. Model fit was good [chi
      2(7) = 12.91, p = 0.07, RMSEA = 0.02, CFI = 1.00, TLI = 0.99, SRMR = 0.01].
      CONCLUSIONS: Attitudes towards OEMH are rather disadvantageous in the studied
      risk group. Implementation of OEMH, therefore, requires a-priori education
      including promotion of awareness, favorable attitudes regarding efficacy and
      usability in a collaborative approach.

PMID- 29189896
TI  - Between a rux and a hard place: evaluating salvage treatment and outcomes in
      myelofibrosis after ruxolitinib discontinuation.
AB  - Ruxolitinib is a JAK1/2 inhibitor that is effective in managing symptoms and
      splenomegaly related to myelofibrosis (MF). Unfortunately, many patients must
      discontinue ruxolitinib, at which time treatment options are not well defined. In
      this study, we investigated salvage treatment options and clinical outcomes among
      MF patients who received and discontinued ruxolitinib outside the context of a
      clinical trial. Among 145 patients who received ruxolitinib, 23 died while on
      treatment, 58 remained on treatment at time of analysis, leaving 64 people
      available for analysis. Development of cytopenias was the most common reason for
      discontinuation (38%) after median treatment time of 3.8 months (mo). The
      majority of patients received some form of salvage therapy after ruxolitinib
      discontinuation (n = 42; 66%), with allogeneic hematopoietic stem cell transplant
      (alloHSCT) (n = 17), being most commonly employed. Lenalidomide, thalidomide,
      hydroxyurea, interferon, and danazol were used with similar frequency. The
      response rate to salvage treatment was 26% (8 responses) and responses were most
      often seen with lenalidomide or thalidomide. Improved outcomes were observed in
      patients who underwent alloHSCT or received salvage therapy compared to those who
      did not receive additional therapy. Median overall survival (OS) after
      ruxolitinib discontinuation was 13 months. These findings show that salvage
      therapy can provide clinical responses after ruxolitinib discontinuation;
      however, these responses are rare and outcomes in this patient population are
      poor. This represents an area of unmet clinical need in MF.

PMID- 29189894
TI  - The importance of an interaction network for proper DNA polymerase zeta
      heterotetramer activity.
AB  - Precisely controlled mechanisms have been evolved to rescue impeded DNA
      replication resulting from encountered obstacles and involve a set of low
      fidelity translesion synthesis (TLS) DNA polymerases. Studies in recent years
      have brought new insights into those TLS polymerases, especially concerning the
      structure and subunit composition of DNA polymerase zeta (Pol zeta). Pol zeta is
      predominantly involved in induced mutagenesis as well as the bypass of
      noncanonical DNA structures, and it is proficient in extending from terminal
      mismatched nucleotides incorporated by major replicative DNA polymerases. Two
      active forms of Pol zeta, heterodimeric (Pol zeta2) and heterotetrameric (Pol
      zeta4) ones, have been identified and studied. Here, in the light of recent
      publications regarding induced and spontaneous mutagenesis and diverse
      interactions within Pol zeta holoenzyme, combined with Pol zeta binding to the
      TLS polymerase Rev1p, we discuss the subunit composition of Pol zeta in various
      cellular physiological conditions. Available data show that it is the
      heterotetrameric form of Pol zeta that is involved both during spontaneous and
      induced mutagenesis, and underline the importance of interactions within Pol zeta
      when an increased Pol zeta recruitment occurs. Understanding Pol zeta function in
      the bypass of DNA obstacles would give a significant insight into cellular
      tolerance of DNA damage, genetic instability and the onset of cancer progression.

PMID- 29189897
TI  - Epstein-Barr virus clonality and plasmacytosis in a patient with atypical
      angioimmunoblastic T cell lymphoma.

PMID- 29189898
TI  - Immunogenicity of recombinant vaccinia virus vaccines co-expressing GP3/GP5 of
      European PRRSV and Cap protein of PCV2 in pigs.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is almost always caused by
      the North American strain of PRRS virus (PRRSV) in China; the European genotype
      of PRRSV has emerged in China. The mixed infection of PRRSV and Porcine
      circovirus type 2 virus (PCV2) are always found in pigs and PRRSV-augmented PCV2
      replication and serious clinical symptoms. Current vaccines cannot protect mixed
      European PRRSV and PCV2 infections. Therefore, the development of a safe and
      effective new vaccine to prevent and control the mixed infection of European
      PRRSV and PCV2 is both urgent and necessary. In this study, we developed a
      recombinant vaccinia vaccine co-expressing the GP3 and GP5 proteins of European
      PRRSV and the ORF2 protein of PCV2 and evaluated the immunogenicity and its
      protective effects and its inactivated vaccine in pigs. The recombinant vaccinia
      vaccine and its inactivated vaccine both elicited significant humoral and
      cellular immune responses with a higher level of specific antibody responses and
      T-lymphocyte proliferation than the control group. Furthermore, the pigs
      inoculated with the recombinant vaccinia vaccine were completely protected
      against challenge with 105 TCID50 of European PRRSV strain LV. These data suggest
      that the recombinant vaccinia vaccine is a potential candidate vaccine against
      European PRRSV and PCV2.

PMID- 29189900
TI  - Hygrocin C from marine-derived Streptomyces sp. SCSGAA 0027 inhibits biofilm
      formation in Bacillus amyloliquefaciens SCSGAB0082 isolated from South China Sea
      gorgonian.
AB  - Several ansamycins have been reported to inhibit bacterial biofilm formation and
      accelerate the eradication of developed biofilms, but little is known about the
      effect of hygrocin C, an ansamycin, on bacterial biofilm formation. Here,
      hygrocin C was isolated from the marine-derived Streptomyces sp. SCSGAA 0027 and
      reported for the first time to be capable of inhibiting the biofilm formation of
      Staphylococcus aureus and Bacillus amyloliquefaciens SCSGAB0082 with the
      production of anti-microbial lipopeptides from South China Sea gorgonian
      Subergorgia suberosa at concentrations of less than minimum inhibitory
      concentrations. Moreover, hygrocin C also promoted the eradication of developed
      biofilms, affected the biofilm architecture, and lowered the extracellular
      polymeric matrix formation, cell motility, and surface hydrophobicity in B.
      amyloliquefaciens, which was in accordance with the inhibition of biofilm
      formation. Furthermore, transcriptome analysis revealed that hygrocin C altered
      the transcripts of several genes associated with bacterial chemotaxis and
      flagellar, two-component system and the synthesis of arginine and histidine,
      which are important for bacterial biofilm formation. In conclusion, hygrocin C
      could be used as a potential biofilm inhibitor against S. aureus and B.
      amyloliquefaciens. But further genetic investigations are needed to provide more
      details for elucidation of the molecular mechanisms responsible for the effects
      of hygrocin C on B. amyloliquefaciens biofilm formation.

PMID- 29189899
TI  - Starter cultures as biocontrol strategy to prevent Brettanomyces bruxellensis
      proliferation in wine.
AB  - Brettanomyces bruxellensis is a common and significant wine spoilage
      microorganism. B. bruxellensis strains generally detain the molecular basis to
      produce compounds that are detrimental for the organoleptic quality of the wine,
      including some classes of volatile phenols that derive from the sequential
      bioconversion of specific hydroxycinnamic acids such as ferulate and p-coumarate.
      Although B. bruxellensis can be detected at any stage of the winemaking process,
      it is typically isolated at the end of the alcoholic fermentation (AF), before
      the staring of the spontaneous malolactic fermentation (MLF) or during barrel
      aging. For this reason, the endemic diffusion of B. bruxellensis leads to
      consistent economic losses in the wine industry. Considering the interest in
      reducing sulfur dioxide use during winemaking, in recent years, biological
      alternatives, such as the use of tailored selected yeast and bacterial strains
      inoculated to promote AF and MLF, are actively sought as biocontrol agents to
      avoid the "Bretta" character in wines. Here, we review the importance of
      dedicated characterization and selection of starter cultures for AF and MLF in
      wine, in order to reduce or prevent both growth of B. bruxellensis and its
      production of volatile phenols in the matrix.

PMID- 29189901
TI  - Elevational distribution and morphological attributes of the entomopathogenic
      fungi from forests of the Qinling Mountains in China.
AB  - Entomopathogenic fungi are considered to be a safe microbiological pesticide
      alternative to chemical control. Efforts are underway to understand precisely
      their taxonomy and natural distribution through mycological and biodiversity
      studies based on molecular markers. Here, we present descriptions of the
      diversity of the entomopathogenic fungi in the genera Metarhizium and Beauveria
      found along the elevational gradients of the Qinling subtropical and temperate
      forests of Shaanxi province in China, using morphological aspects and molecular
      markers. Molecular characterization using the Mz_IGS3 intergenic region revealed
      that Metarhizium isolates phylogenetically clustered in the PARB clade with four
      different distinguishable species, but the 5'-TEF gene allowed only ambiguous
      delimitation of Metarhizium species. Beauveria isolates were characterized by
      sequence analyses of the translation elongation factor 1-alpha and the Bloc
      region. The richness of Metarhizium species decreased with increasing elevation,
      with Metarhizium robertsii s.l. being the most abundant species along the
      elevational gradient. Our bioassay suggests that certain species of Metarhizium
      are significantly pathogenic to the insect model Tenebrio molitor at both the
      adult and larvae stages and could potentially serve as a control of insect pests
      of forests.

PMID- 29189902
TI  - Bacteria-produced ferric exopolysaccharide nanoparticles as iron delivery system
      for truffles (Tuber borchii).
AB  - Iron exopolysaccharide nanoparticles were biogenerated during ferric citrate
      fermentation by Klebsiella oxytoca DSM 29614. Before investigating their effects
      on Tuber borchii ("bianchetto" truffle) mycelium growth and morphology, they were
      tested on human K562 cell line and Lentinula edodes pure culture and shown to be
      non-toxic. Using these nanoparticles as iron supplement, the truffles showed
      extremely efficient iron uptake of over 300 times that of a commercial product.
      This avoided morphological changes in T. borchii due to lack of iron during
      growth and, with optimum nanoparticle dosage, increased growth without cell wall
      disruption or alteration of protoplasmatic hyphal content, the nuclei,
      mitochondria, and rough endoplasmic reticula being preserved. No significant
      modifications in gene expression were observed. These advantages derive from the
      completely different mechanism of iron delivery to mycelia compared to commercial
      iron supplements. The present data, in fact, show the nanoparticles attached to
      the cell wall, then penetrating it non-destructively without damage to cell
      membrane, mitochondria, chromatin, or ribosome. Low dosage significantly improved
      mycelium growth, without affecting hyphal morphology. Increases in hyphal
      diameter and septal distance indicated a healthier state of the mycelia compared
      to those grown in the absence of iron or with a commercial iron supplement. These
      positive effects were confirmed by measuring fungal biomass as mycelium dry
      weight, total protein, and ergosterol content. This "green" method for
      biogenerating iron exopolysaccharide nanoparticles offers many advantages,
      including significant economic savings, without toxic effects on the
      ectomycorrhizal fungus, opening the possibility of using them as iron supplements
      in truffle plantations.

PMID- 29189903
TI  - Comparison of food consumption and nutrient intake assessed with three dietary
      assessment methods: results of the German National Nutrition Survey II.
AB  - PURPOSE: Comparison of food consumption, nutrient intake and underreporting of
      diet history interviews, 24-h recalls and weighed food records to gain further
      insight into specific strength and limitations of each method and to support the
      choice of the adequate dietary assessment method. METHODS: For 677 participants
      (14-80 years) of the German National Nutrition Survey II confidence intervals for
      food consumption and nutrient intake were calculated on basis of bootstrapping
      samples, Cohen's d for the relevance of differences, and intraclass correlation
      coefficients for the degree of agreement of dietary assessment methods. Low
      energy reporters were identified with Goldberg cut-offs. RESULTS: In 7 of 18 food
      groups diet history interviews showed higher consumption means than 24-h recalls
      and weighed food records. Especially mean values of food groups perceived as
      socially desirable, such as fruit and vegetables, were highest for diet history
      interviews. For "raw" and "cooked vegetables", the diet history interviews showed
      a mean consumption of 144 and 109 g/day in comparison with 68 and 70 g/day in 24
      h recalls and 76 and 75 g/day in weighed food records, respectively. For "fruit",
      diet history interviews showed a mean consumption of 256 g/day in comparison with
      164 g/day in 24-h recalls and 147 g/day in weighed food records. No major
      differences regarding underreporting of energy intake were found between dietary
      assessment methods. CONCLUSIONS: With regard to estimating food consumption and
      nutrient intake, 24-h recalls and weighed food records showed smaller differences
      and better agreement than pairwise comparisons with diet history interviews.

PMID- 29189904
TI  - The association of whole and refined grains consumption with psychological
      disorders among Iranian adults.
AB  - PURPOSE: Although several studies have examined the link between different types
      of carbohydrate consumption and depression and anxiety, limited data are
      available linking whole and refined grains consumption to psychological
      disorders. We aimed to investigate the association of whole and refined grains
      consumption with psychological disorders among Iranian adults. METHODS: A total
      of 3172 adult people with age range of 18-55 years were included in this cross
      sectional study. Data on grains consumption were collected using a validated dish
      based 106-item semi-quantitative food frequency questionnaire. To assess
      depression and anxiety, Iranian validated version of Hospital Anxiety and
      Depression Scale (HADS) was applied. Furthermore, psychological distress was
      examined using General Health Questionnaire (GHQ). Psychological disorders were
      defined based on standard criteria. RESULTS: Mean age of participants was 36.5 +/
      7.9 years. Women in the third quartile of whole grains consumption had lower
      odds for having anxiety (OR 0.62, 95% CI 0.45-0.85) compared with those in the
      first quartile. This relationship was also seen even after controlling for
      potential confounders (OR 0.65, 95% CI 0.44-0.96). In contrast, compared with the
      first quartile, women in the highest quartile of refined grains consumption had
      greater odds to have depression (OR 1.76, 95% CI 1.00-3.09) and anxiety (OR 2.03,
      95% CI 1.00-4.10) after adjusting for covariates. Such relationships were not
      observed among men. CONCLUSION: Moderate consumption of whole grain foods was
      inversely associated with anxiety in women, but not in men. Furthermore, we found
      a significant positive association between refined grains consumption, depression
      and anxiety in women.

PMID- 29189906
TI  - Individual variability in the structural properties of neurons in the human
      inferior olive.
AB  - The inferior olive (IO) is the sole source of the climbing fibers innervating the
      cerebellar cortex. We have previously shown both individual differences in the
      size and folding pattern of the principal nucleus (IOpr) in humans as well as in
      the expression of different proteins in IOpr neurons. This high degree of
      variability was not present in chimpanzee samples. The neurochemical differences
      might reflect static differences among individuals, but might also reflect age
      related processes resulting in alterations of protein synthesis. Several
      observations support the latter idea. First, accumulation of lipofuscin, the "age
      pigment" is well documented in IOpr neurons. Second, there are silver- and
      abnormal tau-immunostained intraneuronal granules in IOpr neurons (Ikeda et al.
      Neurosci Lett 258:113-116, 1998). Finally, Olszewski and Baxter (Cytoarchitecture
      of the human brain stem, Second edn. Karger, Basel, 1954) observed an apparent
      loss of IOpr neurons in older individuals. We have further investigated the
      possibility of age-related changes in IOpr neurons using silver- and
      immunostained sections. We found silver-labeled intraneuronal granules in neurons
      of the IOpr in all human cases studied (n = 17, ages 25-71). We did not, however,
      confirm immunostaining with antibodies to abnormal tau. There was individual
      variability in the density of neurons as well as in the expression of the calcium
      binding protein calretinin. In the chimpanzee, there were neither silver-stained
      intraneuronal granules nor irregularities in immunostaining. Overall, the data
      support the hypothesis that in some, but not all, humans there are functional
      changes in IOpr neurons and ultimately cell death. Neurochemical changes of IOpr
      neurons may contribute to age-related changes in motor and cognitive skills
      mediated by the cerebellum.

PMID- 29189905
TI  - Complementary research models and methods to study axonal regeneration in the
      vertebrate retinofugal system.
AB  - Due to the lack of axonal regeneration, age-related deterioration in the central
      nervous system (CNS) poses a significant burden on the wellbeing of a growing
      number of elderly. To overcome this regenerative failure and to improve the
      patient's life quality, the search for novel regenerative treatment strategies
      requires valuable (animal) models and techniques. As an extension of the CNS, the
      retinofugal system, consisting of retinal ganglion cells that send their axons
      along the optic nerve to the visual brain areas, has importantly contributed to
      the current knowledge on mechanisms underlying the restricted regenerative
      capacities and to the development of novel strategies to enhance axonal
      regeneration. It provides an extensively used research tool, not only in amniote
      vertebrates including rodents, but also in anamniote vertebrates, such as
      zebrafish. Indeed, the latter show robust regeneration capacities, thereby
      providing insights into the factors that contribute to axonal regrowth and proper
      guidance, complementing studies in mammals. This review provides an integrative
      and critical overview of the classical and state-of-the-art models and methods
      that have been employed in the retinofugal system to advance our knowledge on the
      signaling pathways underlying the restricted versus robust axonal regeneration in
      rodents and zebrafish, respectively. In vitro, ex vivo and in vivo models and
      techniques to improve the visualization and analysis of regenerating axons are
      summarized. As such, the retinofugal system is presented as a valuable model to
      further facilitate research on axonal regeneration and to open novel therapeutic
      avenues for CNS pathologies.

PMID- 29189907
TI  - Neural circuits underlying jaw movements for the prey-catching behavior in frog:
      distribution of vestibular afferent terminals on motoneurons supplying the jaw.
AB  - Coordinated movement of the jaw is essential for catching and swallowing the
      prey. The majority of the jaw muscles in frogs are supplied by the trigeminal
      motoneurons. We have previously described that the primary vestibular afferent
      fibers, conveying information about the movements of the head, established close
      appositions on the motoneurons of trigeminal nerve providing one of the
      morphological substrates of monosynaptic sensory modulation of prey-catching
      behavior in the frog. The aim of our study was to reveal the spatial distribution
      of vestibular close appositions on the somatodendritic compartments of the
      functionally different trigeminal motoneurons. In common water frogs, the
      vestibular and trigeminal nerves were simultaneously labeled with different
      fluorescent dyes and the possible direct contacts between vestibular afferents
      and trigeminal motoneurons were identified with the help of DSD2 attached to an
      Andor Zyla camera. In the rhombencephalon, an overlapping area was detected
      between the incoming vestibular afferents and trigeminal motoneurons along the
      whole extent of the trigeminal motor nucleus. The vestibular axon collaterals
      formed large numbers of close appositions with dorsomedial and ventrolateral
      dendrites of trigeminal motoneurons. The majority of direct contacts were located
      on proximal dendritic segments closer than 300 um to the somata. The identified
      contacts were evenly distributed on rostral motoneurons innervating jaw-closing
      muscles and motoneurons supplying jaw-opening muscles and located in the caudal
      part of trigeminal nucleus. We suggest that the identified contacts between
      vestibular axon terminals and trigeminal motoneurons may constitute one of the
      morphological substrates of a very quick response detected in trigeminal
      motoneurons during head movements.

PMID- 29189908
TI  - Diffusion tractography reveals pervasive asymmetry of cerebral white matter
      tracts in the bottlenose dolphin (Tursiops truncatus).
AB  - Brain enlargement is associated with concomitant growth of interneuronal
      distance, increased conduction time, and reduced neuronal interconnectivity.
      Recognition of these functional constraints led to the hypothesis that large
      brained mammals should exhibit greater structural and functional brain
      lateralization. As a taxon with the largest brains in the animal kingdom, Cetacea
      provides a unique opportunity to examine asymmetries of brain structure and
      function. In the present study, diffusion tensor imaging and tractography were
      used to investigate cerebral white matter asymmetry in the bottlenose dolphin
      (Tursiops truncatus). Widespread white matter asymmetries were observed with the
      preponderance of tracts exhibiting leftward structural asymmetries. Leftward
      lateralization may reflect differential processing and execution of behaviorally
      variant sensory and motor functions by the cerebral hemispheres. The arcuate
      fasciculus, an association tract linked to human language evolution, was isolated
      and exhibited rightward asymmetry suggesting a right hemisphere bias for
      conspecific communication unlike that of most mammals. This study represents the
      first examination of cetacean white matter asymmetry and constitutes an important
      step toward understanding potential drivers of structural asymmetry and its role
      in underpinning functional and behavioral lateralization in cetaceans.

PMID- 29189910
TI  - Bacterial colonisation of suture material after routine neurosurgical procedures:
      relevance for wound infection.
AB  - BACKGROUND: Wound healing impairment is a serious problem in surgical disciplines
      which may be associated with chronic morbidity, increased cost and patient
      discomfort. Here we aimed to investigate the relevance of bacterial colonisation
      on suture material using polymerase chain reaction (PCR) to detect and
      taxonomically classify bacterial DNA in patients with and without wound healing
      problems after routine neurosurgical procedures. METHODS: Repeat surgery was
      performed in 25 patients with wound healing impairment and in 38 patients with
      well-healed wounds. To determine the presence of bacteria, a 16S rDNA-based PCR
      detection method was applied. Fragments of 500 bp were amplified using universal
      primers which target hypervariable regions within the bacterial 16S rRNA gene.
      Amplicons were separated from each other by single-strand conformation
      polymorphism (SSCP) analysis, and finally classified using Sanger sequencing.
      RESULTS: PCR/SSCP detected DNA of various bacteria species on suture material in
      10/38 patients with well-healed wounds and in 12/25 patients with wound healing
      impairment including Staphylococcus aureus, Staphylococcus epidermidis,
      Propionibacterium acnes and Escherichia coli. Microbiological cultures showed
      bacterial growth in almost all patients with wound healing impairment and
      positive results in PCR/SSCP (10/12), while this was the case in only one patient
      with a well-healed wound (1/10). CONCLUSIONS: Colonisation of suture material
      with bacteria occurs in a relevant portion of patients with and without wound
      healing impairment after routine neurosurgical procedures. Suture material may
      provide a nidus for bacteria and subsequent biofilm formation. Most likely,
      however, such colonisation of sutures is not a general primer for subsequent
      wound infection.

PMID- 29189909
TI  - Behavioral and physiological polymorphism in males of the austral lizard
      Liolaemus sarmientoi.
AB  - Integrative behavioral studies show that the interplay between individual
      physiology and social behavior influences the ecology of the species, ultimately
      affecting individual fitness. Particularly in lizards, color polymorphism is
      associated with differential behaviors and reproductive strategies, which are
      evident in mature males during the mating season. Dominant males generally have
      greater endurance, higher body temperature, and larger bodies than submissive
      males, so they can acquire and defend larger territories and have greater access
      to females for mating. We studied whether the color morphs observed in males of
      one of the world's southernmost reptiles, Liolaemus sarmientoi, are related to
      behavioral variation during agonistic interactions, thermal physiology,
      morphology, and/or locomotor stamina. Liolaemus sarmientoi males exhibit three
      color morphs: red (RR), red-yellow (RY), and yellow (YY). These lizards exhibit
      subtle behavioral displays and we did not observe stamina differences among
      morphs. However, we found that RR males are more aggressive than YY males during
      agonistic encounters. In addition, greater body temperature change during trials,
      higher field body temperatures, and greater head sizes of RR males compared to RY
      or YY indicate that RR is a dominant morph, which may influence their ability to
      acquire and defend territory and tactics for achieving reproductive success.

PMID- 29189911
TI  - Same, same but different!-matching entomological traces to a human food source by
      stable isotope analysis.
AB  - Blow flies are important tools in forensic entomology, as they feed and develop
      on human bodies. This fact can be used to estimate the minimum post mortem
      interval (PMImin), by classifying the age of the immature stages found on
      corpses. The capacity to also be able to classify the age of adult flies, or even
      empty puparia, could increase the timeframe for a PMImin. However, the
      association of older developmental stages, such as adult flies or their empty
      cases, with a human cadaver may be challenged, as such specimens could stem from
      another food source. Analyzing the stable carbon (delta13C) and nitrogen
      (delta15N) isotopes in such specimens could be helpful here, as the isotope
      signatures reflect those of the food sources. We compared the delta15N and
      delta13C signatures of tissue from humans and 12 additional species by elemental
      analyzer-isotope ratio mass spectrometry (EA-IRMS). We did the same for adult
      flies and empty puparia of the blow fly Lucilia sericata, which were derived from
      juvenile stages developed on tissues from the mentioned species. The isotope
      signatures for the adult flies and their empty puparia linearly mirrored the
      isotope signatures for the respective tissues on which they developed as larvae.
      Results such as these are useful to indicate the flies' nutritional history, but
      they do not provide the same kind of evidence that a DNA analysis would. As
      individual dietary habits, global distribution and environmental effects can
      influence isotope ratios, we strongly recommend to analyzing entomological traces
      and muscle tissues of potential donors or for other food sources.

PMID- 29189912
TI  - Cell wall biosynthesis impairment affects the budding lifespan of the
      Saccharomyces cerevisiae yeast.
AB  - The Saccharomyces cerevisiae yeast is one of the most widely used model in
      studies of cellular and organismal biology, including as aging and proliferation.
      Although several constraints of aging and budding lifespan have been identified,
      these processes have not yet been fully understood. Previous studies of aging in
      yeast have focused mostly on the molecular basics of the underlying mechanisms,
      while physical aspects, particularly those related to the cell wall, were rather
      neglected. In this paper, we examine for the first time, to our knowledge, the
      impact of cell wall biosynthesis disturbances on the lifespan in the budding
      yeast. We have used a set of cell wall mutants, including knr4Delta, cts1Delta,
      chs3Delta, fks1Delta and mnn9Delta, which affect biosynthesis of all major cell
      wall compounds. Our results indicated that impairment of chitin biosynthesis and
      cell wall protein mannosylation reduced the budding lifespan, while disruption in
      the 1,3-beta-glucan synthase activity had no adverse effect on that parameter.
      The impact varied in the severity and the most notable effect was observed for
      the mnn9Delta mutant. What was interesting, in the case of the dysfunction of the
      Knr4 protein playing the role of the transcriptional regulator of cell wall
      chitin and glucan synthesis, the lifespan increased significantly. We also report
      the phenotypic characteristics of cell wall-associated mutants as revealed by
      imaging of the cell wall using transmission electron microscopy, scanning
      electron microscopy and atomic force microscopy. In addition, our findings
      support the conviction that achievement of the state of hypertrophy may not be
      the only factor that determines the budding lifespan.

PMID- 29189913
TI  - Association between multimorbidity and mean platelet volume in diabetic patients
      with acute myocardial infarction.
AB  - AIMS: Diabetes mellitus (DM) is one of the most frequently detected conditions in
      multimorbid disease clusters. Platelet activation is one of the key mechanisms
      underlying atherothrombosis in acute myocardial infarction. Available data link
      mean platelet volume (MPV) to poor prognosis not only in cardiovascular and non
      cardiovascular disease. Given the lack of research data on the association
      between disease clusters and MPV, we have set out to investigate the link between
      multimorbidity and MPV in diabetic patients with acute myocardial infarction.
      METHODS: A total of 277 patients with DM and STEMI undergoing primary
      percutaneous coronary intervention were enrolled. Based on the number of
      comorbidities the study population was divided into two groups: group 1 (N = 58)
      with <= 1 comorbidity and group 2 (N = 219) with >= 2 comorbidities. A
      subanalysis was performed within the multimorbidity group: group 2A with two or
      three comorbidities (N = 156) and group 2B with at least four comorbidities (N =
      63). RESULTS: In the study population, 15.9% of patients had one comorbidity, and
      22.0, 34.3, and 22.7% of patients had two, three, or at least four comorbid
      conditions, respectively. Both MPV and PDW were elevated in multimorbid patients
      (9.3 vs 10.8 fl and 9.5 vs 10.3 fl, respectively). The highest platelet volume
      indices were observed in patients with at least four comorbid conditions. There
      was a moderate positive correlation between MPV and the total number of
      comorbidities, the number of CVD comorbidities, and the number of non-CVD
      comorbidities. CONCLUSIONS: These findings indicate that multimorbidity is
      associated with an increase in platelet volume indices. MPV values increased with
      the increasing number of comorbid conditions. Importantly, MPV values were
      elevated in some, but not all CVD and non-CVD conditions.

PMID- 29189914
TI  - Correction to: Population pharmacokinetics of trastuzumab emtansine in previously
      treated patients with HER2-positive advanced gastric cancer (AGC).
AB  - The online version of the original article can be.

PMID- 29189915
TI  - Targeting BRCA1/2 deficient ovarian cancer with CNDAC-based drug combinations.
AB  - PURPOSE: The mechanism of action of CNDAC (2'-C-cyano-2'-deoxy-1-beta-D-arabino
      pentofuranosyl-cytosine) is unique among deoxycytidine analogs because upon
      incorporation into DNA it causes a single strand break which is converted to a
      double strand break after DNA replication. This lesion requires homologous
      recombination (HR) for repair. CNDAC, as the parent nucleoside, DFP10917, and as
      an oral prodrug, sapacitabine, are undergoing clinical trials for hematological
      malignancies and solid tumors. The purpose of this study is to investigate the
      potential of CNDAC for the therapy of ovarian cancer (OC). METHODS: Drug
      sensitivity was evaluated using a clonogenic survival assay. Drug combination
      effects were quantified by median effect analysis. RESULTS: OC cells lacking
      function of the key HR genes, BRCA1 or BRCA2, were more sensitive to CNDAC than
      corresponding HR proficient cells. The sensitization was associated with greater
      levels of DNA damage in response to CNDAC at clinically achievable
      concentrations, manifested as chromosomal aberrations. Three classes of CNDAC
      based drug combinations were investigated. First, the PARP1 inhibitors, rucaparib
      and talazoparib, were selectively synergistic with CNDAC in BRCA1/2 deficient OC
      cells (combination index < 1) at a relatively low concentration range. Second,
      cisplatin and oxaliplatin had additive combination effects with CNDAC
      (combination index ~ 1). Finally, paclitaxel and docetaxel achieved additive cell
      killing effects with CNDAC at concentration ranges of the taxanes similar for
      both BRCA1/2 deficient and proficient OC cells. CONCLUSIONS: This study provides
      mechanistic rationales for combining CNDAC with PARP inhibitors, platinum
      compounds and taxanes in ovarian cancer lacking BRCA1/2 function.

PMID- 29189916
TI  - Improving Efficiency and Quality of the Children's ASD Diagnostic Pathway:
      Lessons Learned from Practice.
AB  - The 'autism diagnosis crisis' and long waiting times for assessment are as yet
      unresolved, leading to undue stress and limiting access to effective support.
      There is therefore a significant need for evidence to support practitioners in
      the development of efficient services, delivering acceptable waiting times and
      effectively meeting guideline standards. This study reports statistically
      significant reductions in waiting times for autism diagnostic assessment
      following a children's health service improvement programme. The average wait
      between referral and first appointment reduced from 14.2 to 10.4 weeks (t(21) =
      4.3, p < 0.05) and between referral and diagnosis shared, reduced from 270 to
      122.5 days, (t(20) = 5.5, p < 0.05). The proportion of girls identified increased
      from 5.6 to 2.7:1. Methods reported include: local improvement action planning;
      evidence based pathways; systematic clinical data gathering and a training plan.
      This is a highly significant finding for many health services wrestling with the
      challenges of demand and capacity for autism diagnosis and assessment.

PMID- 29189917
TI  - The Glasgow Sensory Questionnaire: Validation of a French Language Version and
      Refinement of Sensory Profiles of People with High Autism-Spectrum Quotient.
AB  - Sensory sensitivity peculiarities represent an important characteristic of Autism
      Spectrum Disorders (ASD). We first validated a French language version of the
      Glasgow Sensory Questionnaire (GSQ) (Robertson and Simmons in J Autism Dev Disord
      43(4):775-784, 2013). The GSQ score was strongly positively correlated with the
      Autism-Spectrum Quotient (AQ) (r = 0.81, p < 10-6, n = 245). We further examined
      sensory profiles of groups with high versus low AQ. The high AQ group scored
      higher at the GSQ than the low AQ group for every sensory modality. Moreover, the
      high AQ group showed greater consistency in their patterns of hypersensitivity
      and hyposensitivity between sensory modalities, and stronger correlations between
      hyper and hyposensitivity. Results are discussed in the context of theories
      accounting for atypical sensory perception in ASD.

PMID- 29189918
TI  - Predictors of Satisfaction with Life in Parents of Children with Autism Spectrum
      Disorder.
AB  - This study examined the relationships between autism spectrum disorder (ASD)
      symptoms, care-related activities, and satisfaction with life (SWL) in 184
      parents caring for a child with ASD in New Zealand. The relationships between
      coping styles and SWL were also examined. The parents' SWL scores indicated they
      were slightly dissatisfied with their lives. A stepwise linear regression showed
      three predictors (care-related health problems, carer esteem and financial
      difficulties) explained 47% of the variance in SWL scores. Several coping styles
      were associated with lowered SWL, and only emotional support was related to
      increased SWL. The regression model provides a focus for monitoring parental
      wellbeing, and stresses the importance of recognition and support for the
      substantial responsibilities parents of children with ASD face.

PMID- 29189920
TI  - Politicians lie, so do I.
AB  - This research analyzed whether political leaders make people lie via priming
      experiments. Priming is a non-conscious and implicit memory effect in which
      exposure to one stimulus affects the response to another. Following priming
      theories, we proposed an innovative concept that people who perceive leaders to
      be dishonest (such as liars) are likely to lie themselves. We designed three
      experiments to analyze and critically discussed the potential influence of prime
      effect on lying behavior, through the prime effect of French political leaders
      (including general politicians, presidents and parties). Experiment 1 discovered
      that participants with non-politician-prime were less likely to lie (compared to
      politician-prime). Experiment 2A discovered that, compared to Hollande-prime,
      Sarkozy-prime led to lying behavior both in gravity (i.e., bigger lies) and
      frequency (i.e., lying more frequently). Experiment 2B discovered that
      Republicans-prime yielded an impact on more lying behavior, and Sarkozy-prime
      made such impact even stronger. Overall, the research findings suggest that lying
      can be triggered by external influencers such as leaders, presidents and
      politicians in the organizations. Our findings have provided valuable insights
      into organizational leaders and managers in their personnel management practice,
      especially in the intervention of lying behavior. Our findings also have offered
      new insights to explain non-conscious lying behavior.

PMID- 29189919
TI  - Autistic Symptoms in Children and Adolescents with Gender Dysphoria.
AB  - Studies have shown an increase of symptoms of autism spectrum disorder (ASD) in
      gender dysphoria (GD). Various hypotheses try to explain this possible co
      occurrence (e.g., a role of resistance to change, stereotyped behaviors or
      prenatal testosterone exposure). This study examined ASD symptoms with the
      Children's Social Behavior Questionnaire (CSBQ) in 490 children with GD compared
      to 2507 typically developing (TD) and 196 children with ASD. CSBQ total scores of
      the GD sample were in between scores from the TD and ASD sample. The GD sample
      showed elevated levels of autistic symptomatology on all subdomains, not only on
      stereotyped and resistance to change. Further, no gender differences and
      interaction effects were found on the total CSBQ, making a sole role for prenatal
      testosterone unlikely.

PMID- 29189921
TI  - Lithium Toxicity in Older Adults: a Systematic Review of Case Reports.
AB  - BACKGROUND AND OBJECTIVES: Despite concerns regarding the vulnerability of older
      adults to lithium toxicity, this has not been well studied. This literature
      review aims to characterize the nature of lithium toxicity in older adults, the
      doses and serum lithium levels associated with toxicity, as well as its clinical
      and laboratory manifestations, precipitating factors, management and outcome.
      METHODS: A systematic 10-year search of English articles was conducted using Ovid
      Medline, Embase Classic + Embase, Cochrane Central Register of Controlled Trials
      and PsycINFO. All studies on lithium toxicity in elderly (aged >= 65 years) where
      the dose of lithium or serum lithium level was clearly described, were included.
      RESULTS: There were no clinical trials or cohort studies found. The search
      identified 38 cases of lithium toxicity in older adults with a mean age of 71.4
      years (SD = 5.53). Mean dose of lithium was 675.4 mg/d (SD = 200.66), and mean
      toxic serum concentration was 2.55 mmol/L (SD = 2.22). Manifestations varied,
      with neurotoxicity being the most common, followed by renal and cardiovascular
      toxicity. Polypharmacy (63.2%) and medical comorbidity (76.3%) were common.
      Intravenous hydration and hemodialysis were widely used for treatment with good
      effect. Most patients recovered fully, and only one patient died despite
      treatment. CONCLUSION: In published case reports, the lithium dose was higher
      than recommended for older adults. Polypharmacy and comorbidities appeared to be
      important precipitating factors of lithium toxicity. Regular monitoring of serum
      lithium concentrations and appropriate caution should be exercised, even when
      serum lithium concentrations are within reported therapeutic levels.

PMID- 29189922
TI  - Apathy and its impact on patient outcome in amyotrophic lateral sclerosis.
AB  - Apathy is one of the most common behavioural symptoms of amyotrophic lateral
      sclerosis (ALS), yet there are few studies that have investigated the
      relationship between apathy and quality of life (QOL) as they are experienced by
      the patient. A cohort of 60 ALS patients were evaluated using the Apathy
      Evaluation Scale which measured cognitive, behavioural, emotional and non
      specific symptoms of apathy combined with the Personal Wellbeing Index, a
      multidimensional measure of QOL. The relationship between patient-rated apathy
      and QOL scores, controlling for potential clinical and psychological confounders
      were analysed using univariate and multivariate methods. Apathy was identified in
      30% of ALS patients. Patients with apathy reported higher levels of depression (p
      = 0.0001). Compared to non-apathetic patients, patients with apathy had lower
      overall QOL (p = 0.001), most pronounced in the domains related to achievements
      in life (p = 0.001) and community-connectedness (p = 0.0001). Of the cognitive,
      behavioural, emotional and non-specific manifestations of apathy, only the
      emotional symptoms explained a significant amount of variance in achievements in
      life (p = 0.003) and community-connectedness (p = 0.001). As such, emotional
      manifestations of apathy may underlie worse QOL in ALS patients presenting with
      behavioural impairment. Patient-reported outcomes, particularly those assessing
      psychosocial functioning may be important for demonstrating the efficacy of
      interventions designed to improve QOL in ALS patients with behavioural
      impairment.

PMID- 29189924
TI  - Immobilization in polyvinyl alcohol hydrogel enhances yeast storage stability and
      reusability of recombinant laccase-producing S. cerevisiae.
AB  - OBJECTIVES: To improve the storage stability and reusability of various yeast
      strains and species by immobilization in polyvinyl alcohol (PVA) hydrogel
      particles. RESULTS: Debaryomyces hansenii, Pichia sorbitophila, Saccharomyces
      cerevisiae, Yarrowia lipolytica, and Zygosaccharomyces rouxii were immobilized in
      PVA particles using LentiKats technology and stored in sterile water at 4 
      degrees C. The immobilization improved the survival of all species; however, the
      highest storage stability was achieved for S. cerevisiae and Y. lipolytica which
      survived more than 1 year, in contrast to free cells that survived for only 3
      months. Tests of the reusability of immobilized recombinant laccase-secreting S.
      cerevisiae revealed that the cells were suitable for repetitive use (55 cycles
      during 15 months) even after storage in water at 4  degrees C for 9 months. A
      suitable method for killing immobilized laccase-secreting cells without affecting
      the produced enzyme activity was also developed. CONCLUSIONS: The immobilization
      of yeasts in PVA hydrogel enables long-term, cheap storage with very good cell
      viability and productivity, thus becoming a promising approach for industrial
      applications.

PMID- 29189923
TI  - Congenital myasthenic syndrome with episodic apnoea: clinical, neurophysiological
      and genetic features in the long-term follow-up of 19 patients.
AB  - BACKGROUND: Congenital myasthenic syndrome with episodic apnoea (CMS-EA) is a
      rare but potentially treatable cause of apparent life-threatening events in
      infancy. The underlying mechanisms for sudden and recurrent episodes of
      respiratory arrest in these patients are unclear. Whilst CMS-EA is most commonly
      caused by mutations in CHAT, the list of associated genotypes is expanding.
      METHODS: We reviewed clinical information from 19 patients with CMS-EA, including
      patients with mutations in CHAT, SLC5A7 and RAPSN, and patients lacking a genetic
      diagnosis. RESULTS: Lack of genetic diagnosis was more common in CMS-EA than in
      CMS without EA (56% n = 18, compared to 7% n = 97). Most patients manifested
      intermittent apnoea in the first 4 months of life (74%, n = 14). A degree of
      clinical improvement with medication was observed in most patients (74%, n = 14),
      but the majority of cases also showed a tendency towards complete remission of
      apnoeic events with age (mean age of resolution 2 years 5 months). Signs of
      impaired neuromuscular transmission were detected on neurophysiology studies in
      79% (n = 15) of cases, but in six cases, this was only apparent following
      specific neurophysiological testing protocols (prolonged high-frequency
      stimulation). CONCLUSIONS: A relatively large proportion of CMS-EA remains
      genetically undiagnosed, which suggests the existence of novel causative CMS
      genes which remain uncharacterised. In light of the potential for recurrent life
      threatening apnoeas in early life and the positive response to therapy, early
      diagnostic consideration of CMS-EA is critical, but without specific
      neurophysiology tests, it may go overlooked.

PMID- 29189925
TI  - Overexpression of Sirtuin2 prevents high glucose-induced vascular endothelial
      cell injury by regulating the p53 and NF-kappaB signaling pathways.
AB  - OBJECTIVES: To investigate the potential role and underlying mechanism of
      Sirtuin2 (SIRT2) in regulating high glucose (HG)-induced vascular endothelial
      cell injury by using human umbilical vein endothelial cells (HUVECs). RESULTS:
      SIRT2 mRNA and protein expression levels were decreased in HG-treated HUVECs.
      SIRT2 overexpression increased viability, decreased apoptosis and reduced levels
      of reactive oxygen species in HG-treated HUVECs. SIRT2 overexpression decreased
      TNF-alpha expression (146.5 +/- 22.8 pg TNF-alpha ml-1) relative to that in the
      empty vector group (263.5 +/- 18.5 pg TNF-alpha ml-1) and decreased MCP-1
      expression (63.8 +/- 9.85 pg MCP-1 ml-1) relative to that in the empty vector
      group (105.8 +/- 8.5 pg MCP-1 ml-1). SIRT2 overexpression decreased the
      acetylation of p53 by 33% and decreased the acetylation of NF-kappaB p65 by 58%
      in HG-treated HUVECs. CONCLUSION: SIRT2 prevents HG-induced vascular endothelial
      cell injury through suppressing the p53 and NF-kappaB signaling pathways.

PMID- 29189926
TI  - Long-term H2 photoproduction from starch by co-culture of Clostridium butyricum
      and Rhodobacter sphaeroides in a repeated batch process.
AB  - OBJECTIVES: To prove the possibility of efficient starch photofermentation in co
      culture of heterotrophic and phototrophic bacteria over prolonged period.
      RESULTS: Repeated batch photofermentation of starch was demonstrated in co
      culture Clostridium butyricum and Rhodobacter sphaeroides under microaerobic
      conditions. It continued 15 months without addition of new inoculum or pH
      regulation when using 4-5 g starch l-1 and 0.04 g yeast extract l-1. The complete
      degradation of starch without volatile fatty acids accumulation was shown in this
      co-culture. The average H2 yield of 5.2 mol/mol glucose was much higher than that
      in Clostridium monoculture. The species composition of co-culture was studied by
      q-PCR assay. The concentration of Clostridium cells in prolonged co-culture was
      lower than in monoculture and even in a single batch co-culture. This means that
      Clostridia growth was significantly limited whereas starch hydrolysis still took
      place. CONCLUSION: The prolonged repeated batch photofermentation of starch by co
      culture C. butyricum and R. sphaeroides provided efficient H2 production without
      accumulation of organic acids under conditions of Clostridia limitation.

PMID- 29189927
TI  - Solvent saturation transfer to proteins (SSTP) for structural and functional
      characterization of proteins.
AB  - Protein structure determination using NMR is dependent on experimentally acquired
      distance restraints. Often, however, an insufficient number of these restraints
      are available for determining a protein's correct fold, much less its detailed
      three-dimensional structure. In consideration of this problem, we propose a
      simple means to acquire supplemental structural restraints from protein surface
      accessibilities using solvent saturation transfer to proteins (SSTP), based on
      the principles of paramagnetic chemical-exchange saturation transfer. Here, we
      demonstrate the utility of SSTP in structure calculations of two proteins, TSG101
      and ubiquitin. The observed SSTP was found to be directly proportional to solvent
      accessibility. Since SSTP does not involve the direct excitation of water, which
      compromises the analysis of protein protons entangled in the breadth of the water
      resonance, it has an advantage over conventional water-based magnetization
      transfers. Inclusion of structural restraints derived from SSTP improved both the
      precision and accuracy of the final protein structures in comparison to those
      determined by traditional approaches, when using minimal amounts of additional
      structural data. Furthermore, we show that SSTP can detect weak protein-protein
      interactions which are unobservable by chemical shift perturbations.

PMID- 29189929
TI  - Correction to: The Effect of Natural or Simulated Altitude Training on High
      Intensity Intermittent Running Performance in Team-Sport Athletes: A Meta
      Analysis.
AB  - Page 10, Fig. 2: The filled circle labelled "3" was plotted inaccurately and
      should have been in the "harmful" section of the graph, as shown in the corrected
      version below.

PMID- 29189928
TI  - Sedentary Behavior and Body Weight and Composition in Adults: A Systematic Review
      and Meta-analysis of Prospective Studies.
AB  - BACKGROUND: The cumulative effect of too much sedentary behavior may contribute
      to weight gain and obesity. OBJECTIVE: The aim of this study was to conduct a
      systematic review and meta-analysis of prospective cohorts and randomized
      controlled studies to determine the association between sedentary behavior and
      body weight and obesity in adults. DATA SOURCES AND STUDY SELECTION: Relevant
      studies were identified from searches of the MEDLINE, Embase, AMED and PubMed
      databases up to May 2017, and by manual searches of in-text citations. Studies
      that evaluated the association in adults between sedentary behavior and body
      weight or obesity, while controlling for physical activity, were included.
      Overall, 31 publications met the eligibility criteria, including 23 prospective
      cohort studies with data that could be extracted for a quantitative meta
      analysis, and a single randomized controlled trial. RESULTS: There were no
      significant associations between sedentary behavior and any measure of body
      weight or obesity, with the exception of waist circumference. For the latter
      outcome, over a 5-year follow-up period, each 1 h per day increase-from baseline
      to follow-up-in sedentary behavior was associated with a 0.02 mm [95% confidence
      interval (CI) 0.01-0.04; p = 0.001) increase in waist circumference. The odds
      ratio of becoming overweight or obese was 1.33 (95% CI 1.11-1.60; p = 0.001) in
      the highest compared with lowest categories of sedentary behavior. CONCLUSIONS:
      Meta-analysis of data from prospective cohort studies showed small, inconsistent
      and non-significant associations between sedentary behavior and body weight.

PMID- 29189930
TI  - Periodization Theory: Confronting an Inconvenient Truth.
AB  - Periodization theory has, over the past seven decades, emerged as the preeminent
      training planning paradigm. The philosophical underpinnings of periodization
      theory can be traced back to the integration of diverse shaping influences,
      whereby coaching beliefs and traditions were blended with historically available
      scientific insights and contextualized against pervading social planning models.
      Since then, many dimensions of elite preparation have evolved significantly, as
      driven by a combination of coaching innovations and science-led advances in
      training theory, techniques, and technologies. These advances have been
      incorporated into the fabric of the pre-existing periodization planning
      framework, yet the philosophical assumptions underpinning periodization remain
      largely unchallenged and unchanged. One particularly influential academic sphere
      of study, the science of stress, particularly the work of Hans Selye, is
      repeatedly cited by theorists as a central pillar upon which periodization theory
      is founded. A fundamental assumption emanating from the early stress research is
      that physical stress is primarily a biologically mediated phenomenon: a
      presumption translated to athletic performance contexts as evidence that
      mechanical training stress directly regulates the magnitude of subsequent
      'fitness' adaptations. Interestingly, however, since periodization theory first
      emerged, the science of stress has evolved extensively from its historical roots.
      This raises a fundamental question: if the original scientific platform upon
      which periodization theory was founded has disintegrated, should we critically re
      evaluate conventional perspectives through an updated conceptual lens? Realigning
      periodization philosophy with contemporary stress theory thus presents us with an
      opportunity to recalibrate training planning models with both contemporary
      scientific insight and progressive coaching practice.

PMID- 29189931
TI  - Preoperative sentinel lymph node localization in vulvar cancer: preliminary
      experience with inguinal intradermal contrast-enhanced ultrasound.
AB  - OBJECTIVE: To evaluate the feasibility and diagnostic performance of intradermal
      contrast-enhanced ultrasound (CEUS) sentinel lymph node (SLN) procedure in vulvar
      cancer. METHODS: Twelve consecutive patients with vulvar cancer underwent
      preoperatively inguinal CEUS SLN examination and guide wire marking of the
      enhanced lymph nodes. Altogether, 20 groins were examined with CEUS contrast
      agent injections including 8 bilateral groins due to midline tumours. One groin
      was excluded due to previous inguinal surgery. The results of the CEUS
      examinations were compared to conventional SLN biopsy using radiocolloid
      scintigraphy and/or methylene blue dye and final postoperative histopathology.
      RESULTS: The inguinal sentinel CEUS procedure had a technical success rate of
      94.7% (18/19 injections) for identifying a potential inguinal SLN. Conventional
      SLN biopsy using lymphoscintigraphy and/or methylene blue dye was successfully
      performed in 16 groins. Compared to conventional SLN biopsy, the overall
      sensitivity was 81.2% (13/16 injections). Additionally, CEUS detected enhancing
      SLNs in two cases when traditional SLN procedure failed to do so. All metastatic
      SLNs (n = 5) were correctly identified by CEUS procedure. CONCLUSIONS:
      Intradermal CEUS SLN localization can be applied in the inguinal lymphatic region
      in patients with vulvar cancer. Further studies are needed to verify the clinical
      value of this method. KEY POINTS: * CEUS is a feasible method for inguinal SLN
      detection in vulvar cancer * All metastatic inguinal SLNs were identified by CEUS
      procedure * Further studies are needed to verify the clinical value of this
      method.

PMID- 29189932
TI  - Contrast-enhanced US for characterization of focal liver lesions: a comprehensive
      meta-analysis.
AB  - OBJECTIVES: This meta-analysis was performed to evaluate the accuracy of contrast
      enhanced ultrasound (CEUS) in differentiating malignant from benign focal liver
      lesions (FLLs). METHODS: Cochrane Library, PubMed and Web of Science databases
      were systematically searched and checked for studies using CEUS in
      characterization of FLLs. Data necessary to construct 2*2 contingency tables were
      extracted from included studies. The QUADAS tool was utilized to assess the
      methodologic quality of the studies. Meta-analysis included data pooling,
      subgroup analyses, meta-regression and investigation of publication bias was
      comprehensively performed. RESULTS: Fifty-seven studies were included in this
      meta-analysis and the overall diagnostic accuracy in characterization of FLLs was
      as follows: pooled sensitivity, 0.92 (95%CI: 0.91-0.93); pooled specificity, 0.87
      (95%CI: 0.86-0.88); diagnostic odds ratio, 104.20 (95%CI: 70.42-154.16). Subgroup
      analysis indicated higher diagnostic accuracy of the second-generation contrast
      agents (CAs) than the first-generation CA (Levovist; DOR: 118.27 vs. 62.78).
      Furthermore, Sonazoid demonstrated the highest diagnostic accuracy among three
      major CAs (SonoVue, Levovist and Sonazoid; DOR: 118.82 vs. 62.78 vs. 227.39). No
      potential publication bias was observed of the included studies. CONCLUSION: CEUS
      is an accurate tool to stratify the risk of malignancy in FLLs. The second
      generation CAs, especially Sonazoid may greatly improve diagnostic performance.
      KEY POINTS: * CEUS shows excellent diagnostic accuracy in differentiating
      malignant from benign FLLs. * The second-generation CAs have higher diagnostic
      accuracy than first-generation CAs. * Sonazoid demonstrates the highest
      diagnostic accuracy among three major CAs.

PMID- 29189933
TI  - Cardiac structure and function in elite Native Hawaiian and Pacific Islander
      Rugby Football League athletes: an exploratory study.
AB  - The aim of this exploratory study was to define the Athletes Heart (AH) phenotype
      in Native Hawaiian & Pacific Islander (NH&PI) Rugby Football League (RFL)
      athletes. Specifically, (1) to describe conventional echocardiographic indices of
      left ventricle (LV) and right ventricle (RV) structure and function in NH&PI RFL
      players and matched RFL Caucasian controls (CC) and (2) to demonstrate LV and RV
      mechanics in these populations. Ethnicity is a contributory factor to the
      phenotypical expression of the AH. There are no data describing the cardiac
      phenotype in NH&PI athletes. Twenty-one male elite NH&PI RFL athletes were
      evaluated using conventional echocardiography and myocardial speckle tracking,
      allowing the assessment of global longitudinal strain (epsilon) and strain rate
      (SR); and basal, mid and global radial and circumferential epsilon and SR. Basal
      and apical rotation and twist were also assessed. Results were compared with age
      matched Caucasian counterparts (CC; n = 21). LV mass [42 +/- 9 versus 37 +/- 4
      g/(m2.7)], mean LV wall thickness (MWT: 9.5 +/- 0.7 and 8.7 +/- 0.4 mm), relative
      wall thickness (RWT: 0.35 +/- 0.04 and 0.31 +/- 0.03) and RV wall thickness (5 +/
      1 and 4 +/- 1 mm, all p < 0.05) were greater in NH&PI compared with CC. LV and
      RV cavity dimensions and standard indices of LV and RV systolic and diastolic
      function were similar between groups. NH&PI demonstrated reduced peak LV mid
      circumferential epsilon and early diastolic SR, as well as reduced global radial
      epsilon. There was reduced basal rotation at 25-35% systole, reduced apical
      rotation at 25-40% and 60-100% systole and reduced twist at 85-95% systole in
      NH&PI athletes. There were no differences between the two groups in RV wall
      mechanics. When compared to Caucasian controls, NH&PI rugby players have a
      greater LV mass, MWT and RWT with concomitant reductions in circumferential and
      twist mechanics. This data acts to prompt further research in NH&PI athletes.

PMID- 29189934
TI  - Mechanical deformation in adult patients with unrepaired aortic coarctation.
AB  - Aortic coarctation is a congenital heart disease that causes an increased left
      ventricular afterload, resulting in increased systolic parietal tension,
      compensatory hypertrophy, and left ventricular systolic and diastolic
      dysfunction. The speckle tracking is a new echocardiographic technique that
      allows the detection of subclinic left ventricular systolic dysfunction. The aim
      of this study was to detect early left ventricular dysfunction using mechanical
      deformation by echocardiography in adults with un-repaired aortic coarctation. A
      total of 41 subjects were studied, 20 patients with aortic coarctation and 21
      control subjects, 21 women (51.2%), with an average age of 30 +/- 10 years. All
      patients with aortic coarctation had systemic arterial hypertension (p < 0.001).
      Seventy percent (14/20) of the patients had bicuspid aortic valve. Statistically
      significance (p < 0.005) were found in left ventricular mass index, E/e ratio,
      pulmonary artery systolic pressure and peak velocity and maximum gradient of the
      aortic valve. The global longitudinal deformation of the left ventricle in
      patients with aortic coarctation was significative decreased, p < 0.001. The
      ejection fraction and the global longitudinal deformation of the left ventricle
      were significantly lower in patients with aortic coarctation compared to the
      control group, p < 0.003, p < 0.001, respectively. The subgroup of patients with
      coarctation and left ventricular ejection fraction < 55% had a marked decrease in
      global longitudinal strain (- 15.9 +/- 4%). The radial deformation was increased
      in patients with aortic coarctation and showed a trend to be significant (r =
      0.421; p < 0.06). A significant negative correlation was observed between the
      global longitudinal deformation and left ventricular mass index (r = 0.54; p =
      0.01) in the aortic coarctation group. The patients with aortic coarctation and
      left ventricular hypertrophy had marked reduction of left ventricular global
      longitudinal deformation (- 16%, p < 0.05). In our study patients with normal
      left ventricular ejection fraction had abnormal global longitudinal deformation
      and also the increased left ventricular mass was related with a decreased left
      ventricular global longitudinal deformation as a sign of subclinical systolic
      dysfunction.

PMID- 29189935
TI  - The physiology of the Tambaqui (Colossoma macropomum) at pH 8.0.
AB  - The Tambaqui is a model neotropical teleost which is of great economic and
      cultural importance in artisanal fisheries and commercial aquaculture. It thrives
      in ion-poor, often acidic Amazonian waters and exhibits excellent regulation of
      physiology down to water pH 4.0. Curiously, however, it is reported to perform
      poorly in aquaculture at pH 8.0, an only slightly alkaline pH which would be
      benign for most freshwater fish. In initial experiments with Tambaqui of
      intermediate size (30-50 g), we found that ammonia excretion rate was unchanged
      at pH 4, 5, 6, and 7, but elevated after 20-24 h at pH 8, exactly opposite the
      pattern seen in most teleosts. Subsequent experiments with large Tambaqui (150
      300 g) demonstrated that only ammonia, and not urea excretion was increased at pH
      8.0, and that the elevation was proportional to a general increase in MO2. There
      was an accompanying elevation in net acidic equivalent excretion and/or basic
      equivalent uptake which occurred mainly at the gills. Net Na+ balance was little
      affected while Cl- balance became negative, implicating a disturbance of Cl-
      versus base exchange rather than Na+ versus acid exchange. Arterial blood pH
      increased by 0.2 units at pH 8.0, reflecting combined metabolic and respiratory
      alkaloses. Most parameters recovered to control levels by 18-24 h after return to
      pH 6.0. With respect to large Tambaqui, we conclude that a physiology adapted to
      acidic pH performs inappropriately at moderately alkaline pH. In small Tambaqui
      (4-15 g), the responses were very different, with an initial inhibition of
      ammonia excretion rate at pH 8.0 followed by a subsequent restoration of control
      levels. Elevated ammonia excretion rate occurred only after return to pH 6.0.
      Furthermore, MO2, plasma cortisol, and branchial vH+ATPase activities all
      declined during pH 8.0 exposure in small Tambaqui, in contrast to the responses
      in larger fish. Overall, small Tambaqui appear to cope better at pH 8.0, a
      difference that may correlate with their natural history in the wild.

PMID- 29189936
TI  - P2Y14 receptor activation decreases interleukin-6 production and glioma GL261
      cell proliferation in microglial transwell cultures.
AB  - Gliomas are rich in extracellular nucleotides that modulate glioma cell
      production of multiple cytokines including interleukin (IL)-6, which strongly
      contributes to glioma cell proliferation. However, little is known about how
      nucleotide signaling modulates microglial/macrophage (MG/MP) cytokine production
      in the context of gliomas, nor how MG/MP purinergic P2 receptor expression
      changes in the tumor micro-environment. We hypothesized that: (1) expression of
      key P2Y receptors will be augmented in glioma-derived MG/MP, and (2) selective
      activation of these receptors in vitro will regulate microglial production of IL
      6 and glioma cell proliferation. We tested these hypotheses using the murine
      GL261 glioma model. Compared to MG/MP isolated from the normal brain tissue,
      CD11b+ cells isolated from GL261 tumors expressed higher levels of several P2
      receptors, including P2Y14 receptors. To evaluate microglial P2Y14 receptor
      function in the context of tumor cells, we first cultured N9 microglia in
      transwells with GL261 cells and found that microglial P2Y14 mRNA levels were
      similarly increased in transwell cultures. GL261 cells did not express detectable
      P2Y14 levels either when they were cultured alone or in transwell cultures with
      N9 cells. Selective P2Y14 receptor activation with UDP-glucose (UDPG) did not
      affect IL-6 levels in either cell type cultured alone, but in transwell cultures,
      UDPG decreased IL-6 protein levels in the medium. Application of conditioned
      medium from UDPG-treated microglia reduced GL261 cell proliferation. Together,
      these data suggest that P2Y14 receptors may be a key a receptor involved in
      glioma cell-MG/MP communication in the tumor environment.

PMID- 29189937
TI  - Bioactive focus in conformational ensembles: a pluralistic approach.
AB  - Computational generation of conformational ensembles is key to contemporary drug
      design. Selecting the members of the ensemble that will approximate the
      conformation most likely to bind to a desired target (the bioactive conformation)
      is difficult, given that the potential energy usually used to generate and rank
      the ensemble is a notoriously poor discriminator between bioactive and non
      bioactive conformations. In this study an approach to generating a focused
      ensemble is proposed in which each conformation is assigned multiple rankings
      based not just on potential energy but also on solvation energy, hydrophobic or
      hydrophilic interaction energy, radius of gyration, and on a statistical
      potential derived from Cambridge Structural Database data. The best ranked
      structures derived from each system are then assembled into a new ensemble that
      is shown to be better focused on bioactive conformations. This pluralistic
      approach is tested on ensembles generated by the Molecular Operating
      Environment's Low Mode Molecular Dynamics module, and by the Cambridge
      Crystallographic Data Centre's conformation generator software.

PMID- 29189939
TI  - Successional convergence in experimentally disturbed intertidal communities.
AB  - Determining the causes of variation in community assembly is a central question
      in ecology. Analysis of beta-diversity can provide insight by relating the extent
      of regional to local variation in diversity, allowing inference of the relative
      importance of deterministic versus stochastic processes. We investigated the
      effects of disturbance timing on community assembly at three distinct regions
      with varying environmental conditions: Northern Portugal, Azores and Canaries. On
      the lower rocky intertidal, quadrats were experimentally cleared of biota at
      three distinct times of the year and community assembly followed for 1 year.
      Similar levels of alpha- and gamma-diversity were found in all regions, which
      remained constant throughout succession. When Jaccard (incidence-based) and Bray
      Curtis (abundance-based) metrics were used, beta-diversity (the mean
      dissimilarity among plots cleared at the different times) was larger during early
      stages of community assembly but decreased over time. The adaptation of the Raup
      Crick's metric, which accounts for changes in species richness, showed that the
      structure of assemblages disturbed at different times of the year was similar to
      the null model of random community assembly during early stages of succession but
      became more similar than expected by chance. This pattern was observed in all
      regions despite differences in the regional species pool, suggesting that
      priority effects are likely weak and deterministic processes determine community
      structure despite stochasticity during early stages of community assembly.

PMID- 29189938
TI  - Trans-generational but not early life exposure to stressors influences offspring
      morphology and survival.
AB  - Environmental changes, such as the introduction of non-native species, can impose
      novel selective pressures. This can result in changes in fitness-relevant traits
      within an individual's lifetime or across multiple generations. We investigated
      the effects of early life versus trans-generational exposure to a predatory
      invasive insect stressor, the red imported fire ant (Solenopsis invicta), on the
      morphology and survival of the eastern fence lizard (Sceloporus undulatus). We
      captured gravid lizards from high-stress populations with long histories of
      invasion by fire ants and from uninvaded sites. Resulting hatchlings were exposed
      weekly to one of the three treatments until they reached maturity (42 weeks): (1)
      sub-lethal attack by fire ants; (2) topical application of the stress-relevant
      hormone, corticosterone (CORT), to mimic the stress of fire ant attack; or (3)
      control handling. Exposure to post-natal early life stress (fire ants or CORT)
      did not interact with a population's evolutionary history of stress to affect
      morphology or survival and early life stress did not affect these fitness
      relevant traits. However, morphology and survival were associated with the
      lizards' evolutionary history of exposure to fire ants. Offspring of lizards from
      fire ant invaded sites had longer and faster growing hind-limbs, gained body
      length and lost condition more slowly in the first 16 weeks, and had lower in-lab
      survival to 42 weeks, compared to lizards from uninvaded sites. These results
      suggest that a population's history of stress/invasion caused by fire ants during
      ca. 38 generations may be more important in driving survival-relevant traits than
      are the early life experiences of an organism.

PMID- 29189941
TI  - Vortioxetine: Clinical Pharmacokinetics and Drug Interactions.
AB  - Vortioxetine is a novel antidepressant with multimodal activity currently
      approved for the treatment of major depressive disorder. Vortioxetine is orally
      administered once daily at 5- to 20-mg doses. The pharmacokinetics of
      vortioxetine are linear and dose proportional, with a mean terminal half-life of
      approximately 66 h and steady-state plasma concentrations generally achieved
      within 2 weeks of dosing. The mean absolute oral bioavailability of vortioxetine
      is 75%. No food effect on pharmacokinetics was observed. Vortioxetine is
      metabolized by cytochrome P450 enzymes and subsequently by uridine diphosphate
      glucuronosyltransferase. The major metabolite is pharmacologically inactive, and
      the minor pharmacologically active metabolite is not expected to cross the blood
      brain barrier, making the parent compound primarily responsible for in-vivo
      activity. No clinically relevant differences were observed in vortioxetine
      exposure by sex, age, race, body size, and renal or hepatic function. Dose
      adjustment is only recommended for cytochrome P450 2D6 poor metabolizers based on
      polymorphism of the cytochrome P450 enzymes involved. Similarly, except for
      bupropion, a strong cytochrome P450 2D6 inhibitor, and rifampin, a broad
      cytochrome P450 inducer, co-administration of other drugs evaluated did not
      affect the vortioxetine exposure or safety profile in any clinically meaningful
      way. Pharmacodynamic studies demonstrated that vortioxetine achieved high levels
      of serotonin transporter occupancy in relevant brain areas, affected
      neurotransmitter levels in the cerebrospinal fluid, and modified abnormal resting
      state networks in the brain over the therapeutic dose range. Overall,
      vortioxetine can be administered in most populations studied to date without
      major dose adjustments; however, dose adjustments should be considered on a
      patient-by-patient basis.

PMID- 29189940
TI  - The relationship between dietary protein content, body condition, and Delta15N in
      a mammalian omnivore.
AB  - Seasonal reductions in food availability may cause animals to catabolize
      endogenous tissue and the resulting loss of lean mass can hinder their ability to
      forage and reproduce. While several studies have considered nitrogen isotopes
      (delta15N) as an indicator of catabolism, relationships between protein intake,
      body condition, and tissue delta15N have not been assessed simultaneously in
      controlled conditions. We conducted a feeding experiment on laboratory mice (Mus
      musculus) to test the effects of low (5%) versus high (30-40%) dietary protein
      content on lean mass, fat mass, and tissue delta15N. This approach enables the
      distinction between use of exogenous and endogenous nitrogen, illuminating a
      framework of protein metabolism and tissue synthesis. As expected, lean mass and
      body fat were lower in mice fed low-protein diets. Nitrogen isotope
      discrimination (Delta15N) between blood plasma-diet and liver-diet did not differ
      between diet treatments. In contrast, Delta15N for hair decreased while Delta15N
      for muscle and RBC increased in the low-protein treatment. These patterns suggest
      that animals in negative nitrogen balance catabolize labile endogenous protein
      (e.g., muscle) to maintain vital tissues (e.g., liver) required to survive.
      Consequently, muscle and RBC delta15N values appear to be the most useful in
      assessing the nutritional state of animals. Our combination of direct
      measurements of body condition with delta15N analysis suggest how nitrogen
      isotopes can be better used as tracers of catabolic and anabolic activity by
      demonstrating connections between tissue-specific metabolic processes and
      Delta15N, thus refining the application of delta15N as a tool for assessing
      nitrogen balance in wild animals.

PMID- 29189943
TI  - Relieving one's relatives from the burdens of care.
AB  - It has been proposed that an old and ill person may have a 'duty to die', i.e. to
      refuse life-saving treatment or to end her own life, when she is dependent on the
      care of intimates and the burdens of care are becoming too heavy for them. In
      this paper I argue for three contentions: (1) You cannot have a strict duty to
      die, correlating to a claim-right of your relatives, because if they reach the
      point at which the burdens of care are larger than you can reasonably expect them
      to take, the natural conclusion is that their duty ends. (2) They may be
      prepared, however, to go on caring for you beyond that point. In that case your
      responsibility for their wellbeing may require you to refuse this care, even if
      this results in a situation for you in which death will be preferable to
      continued life. (3) If this is the correct understanding of your
      responsibilities, the objection that in the context of family life the burdens of
      care attached to one family member's valued existence can never be 'too heavy',
      fails. It postulates unlimited concern on one side and a total lack of concern on
      the other.

PMID- 29189944
TI  - The ultrastructural alterations in the lens capsule and epithelium in eyes with
      traumatic white cataract.
AB  - PURPOSE: To demonstrate the morphological and physiological characteristics of
      lens epithelial cells (LECs) in patients with traumatic cataract using
      transmission electron microscopy (TEM) to further understand penetrating ocular
      injury-induced cataract morphology and epithelial repair mechanisms involved at a
      cellular level. METHODS: This is a prospective international study. Sixteen eyes
      of 16 consecutive patients who were diagnosed as traumatic white cataracts
      following the anterior lens capsule perforation and 13 eyes of 13 patients with
      idiopathic posterior subcapsular cataract were included to the study. The
      anterior lens capsules (aLCs: basement membrane and associated LECs) were
      obtained from cataract surgery and prepared for TEM. RESULTS: Two prominent cell
      types were observed in all aLCs of the traumatic cases: degenerated type LECs
      having variable sized intraepithelial vacuoles close to injury site and normal
      appearing LECs having an euchromatic nucleus distant from the injury site. In
      control group, the LECs and all their elements were in normal ultrastructural
      pattern except some small intraepithelial vacuoles, which were fewer and smaller
      than the vacuoles in the degenerated LECs of the traumatic group. CONCLUSIONS:
      The ultrastructural findings of our cases support that traumatically induced
      dysfunction of the lens epithelium may lead to an edema in superficial cortical
      lens fibers that subsequently undergo degeneration and produce a localized zone
      of vacuolization.

PMID- 29189945
TI  - Could adverse effects and complications of selective laser trabeculoplasty be
      decreased by low-power laser therapy?
AB  - Selective laser trabeculoplasty (SLT) has been used for treatment of primary open
      angle glaucoma, ocular hypertension, pigmenter and pseudoexfoliative glaucoma
      being considered a low-risk procedure. Therefore, transitory and permanent
      adverse effects have been reported, including corneal changes, subclinical edema,
      and reduction in endothelial cells and in central corneal thickness. Despite
      rarer, serious corneal complications after SLT can be permanent and lead to
      visual impairment, central corneal haze, opacity and narrowing. The mechanism
      involves increase of vasoactive and chemotactic cytokines causing inflammatory
      infiltrate, destruction of stromal collagen by fibroblasts and increase of matrix
      metalloproteinases type 2, which impair reepithelization. SLT also increases free
      radical production and reduces antioxidant enzymes, resulting in endothelium
      damages. Low-power laser therapy (LPLT) has been used in regenerative medicine
      based on its biostimulatory and anti-inflammatory effects. Biostimulation occurs
      through the interaction of laser photons with cytochrome C oxidase enzyme, which
      activates intracellular biochemical cascades causing synthesis of a number of
      molecules related to anti-inflammatory, regenerative effects, pain relief and
      reduction in edema. It has been showed that LPLT reduces gene expression related
      to pro-inflammatory cytokines and matrix metalloproteinases, and it increases
      expression of growth factors related to its proliferative and healing actions.
      Although radiations emitted by low-power lasers are considered safe and able to
      induce therapeutic effects, researches based on experimental models for glaucoma
      could bring important data if LPLT could be an alternative approach to improve
      acceptation for patients undergoing SLT.

PMID- 29189942
TI  - The Conspicuity of CRISPR-Cpf1 System as a Significant Breakthrough in Genome
      Editing.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR
      associated protein (Cas) is a microbial adaptive immune system. CRISPR-Cas
      systems are classified into two main classes and six types. Cpf1 is a putative
      type V (class II) CRISPR effector, which has revolutionized the genome editing
      approaches through multiple distinct features such as using T-rich protospacer
      adjacent motif, applying a short guide RNA lacking trans-activating crRNA,
      introducing a staggered double-strand break, and possessing RNA processing
      activity in addition to DNA nuclease activity. In the present review, we attempt
      to highlight most recent advances in CRISPR-Cpf1 (CRISPR-Cas12a) system in
      particular, considering ground expeditions of the nature and the biology of this
      system, introducing novel Cpf1 variants that have broadened the versatility and
      feasibility of CRISPR-Cpf1 system, and lastly the great impact of the CRISPR-Cpf1
      system on the manipulation of the genome of prokaryotic, mammalian, and plant
      models is summarized. With regard to recent developments in utilizing the CRISPR
      Cpf1 system in genome editing of various organisms, it can be concluded with
      confidence that this system is a reliable molecular toolbox of genome editing
      approaches.

PMID- 29189946
TI  - Treatment results in aphakic patients with glaucoma following congenital cataract
      surgery.
AB  - PURPOSE: To evaluate the clinical findings and possible risk factors of patients
      with aphakic glaucoma following congenital cataract surgery and identify the
      factors affecting response to glaucoma treatment. METHODS: A retrospective chart
      review of 173 patients was performed who underwent congenital cataract surgery
      before the age of 12 months and 40 eyes of 25 patients with aphakic glaucoma were
      enrolled. Age of the patients at the time of the cataract surgery, postoperative
      complications, additional ocular pathologies and the type of glaucoma treatment
      needed were investigated. RESULTS: Mean age of 25 patients at the time of
      cataract surgery was 3.31 +/- 2.28 (range 1-11) months with a mean follow-up
      period of 79 +/- 30.5 (32-176) months. Out of 40 eyes, medical therapy was
      effective in 20 (50%) eyes, whereas 20 (50%) eyes needed surgery for glaucoma. In
      these 20 eyes, 6 (30%) eyes underwent only 1, 4 (20%) eyes underwent 2 and 10
      (50%) eyes underwent 3 or more procedures. Age at the time of cataract surgery,
      pupillary membrane formation and additional ocular pathologies were not
      significantly associated both with the need for glaucoma surgery or the number of
      operations (p >= 0.05). CONCLUSION: Aphakic glaucoma following congenital
      cataract surgery is a serious complication which requires surgery in half (50%)
      of the patients. Usually, more than one surgical procedure (70%) is needed. It
      can be detected even years after cataract surgery (range 0.3-94 months), so long
      term careful follow-up is necessary.

PMID- 29189947
TI  - Time and frequency components of ERG responses in retinitis pigmentosa.
AB  - PURPOSE: To evaluate the effects of retinitis pigmentosa (RP) on time, frequency,
      and time-frequency components of Xenon flash ERG signals using Fourier and
      wavelet transforms. METHODS: Xenon flash ERG was done in 18 eyes of nine RP
      patients and 20 normal eyes. After examining latency and amplitude, Fourier and
      wavelet transforms were performed using MATLAB software. Then, we extracted the
      mode frequency from the Fourier transform and main frequencies and their
      occurrence time from the wavelet transform. Finally, mean differences were
      analyzed using statistical tests. RESULTS: The results indicated increased
      latency and reduced ERG wave amplitude, no significant inter-group difference in
      the average mode frequency, and significant reduction in main signal frequencies
      and their increased occurrence times. Also one or two of the three main
      frequencies had disappeared in more advanced cases. CONCLUSION: Retinitis
      pigmentosa can induce changes in ERG time and time-frequency components. Impacted
      areas can be identified more accurately by wavelet transform and converting
      scales to frequencies.

PMID- 29189949
TI  - ?

PMID- 29189948
TI  - 11th European Headache Federation Congress jointly with 31st Congress of the
      Italian Society for the Study of Headaches : Rome, Italy. 01-03 December 2017.

PMID- 29189950
TI  - Cost assessment of a new oral care program in the intensive care unit to prevent
      ventilator-associated pneumonia.
AB  - OBJECTIVES: Ventilator-associated pneumonia (VAP) is the most frequent hospital
      acquired infections in intensive care units (ICU). In the bundle of care to
      prevent the VAP, the oral care is very important strategies, to decrease the
      oropharyngeal bacterial colonization and presence of causative bacteria of VAP.
      In view of the paucity of medical economics studies, our objective was to
      determine the cost of implementing this oral care program for preventing VAP.
      MATERIALS AND METHODS: In five ICUs, during period 1, caregivers used a foam
      stick for oral care and, during period 2, a stick and tooth brushing with
      aspiration. Budgetary effect of the new program from the hospital's point of view
      was analyzed for both periods. The costs avoided were calculated from the
      incidence density of VAP (cases per 1000 days of intubation). The cost study
      included device cost, benefit lost, and ICU cost (medication, employer and
      employee contributions, blood sample analysis...). RESULTS: A total of 2030
      intubated patients admitted to the ICUs benefited from oral care. The cost of
      implementing the study protocol was estimated to be ?11,500 per year. VAP rates
      decreased significantly between the two periods (p1 = 12.8% and p2 = 8.5%, p =
      0.002). The VAP revenue was ranged from ?28,000 to ?45,000 and the average cost
      from ?39,906 to ?42,332. The total cost assessment calculated was thus around
      ?1.9 million in favor of the new oral care program. CONCLUSION AND CLINICAL
      RELEVANCE: Our study showed that the implementation of a simple strategy improved
      the quality of patient care is economically viable. TRIAL REGISTRATION:
      NCT02400294.

PMID- 29189951
TI  - Ticks and bacterial tick-borne pathogens in Piemonte region, Northwest Italy.
AB  - A molecular screening for tick-borne pathogens was carried out in engorged and in
      questing ticks collected in Verbano Cusio Ossola county, Piemonte region, Italy.
      Engorged ticks were removed from wild and domestic animal hosts. The most
      abundant and common tick species in the area was Ixodes ricinus (192 adults, 907
      nymphs). Few individuals of Ixodes hexagonus (15) and Rhipicephalus sanguineus
      (7) were found among the ticks removed from domestic animals (46 examined ticks).
      The presence of Rickettsia spp., Borrelia burgdorferi sensu latu, Francisella
      tularensis and Coxiella burnetii was evaluated by PCR and sequencing in 392
      individuals of I. ricinus (adult and nymphal stages) and 22 individuals of the
      two other tick species. Five Borrelia species (i.e. B. burgdorferi sensu stricto,
      B. garinii, B. afzelii, B. valaisiana and B. lusitaniae), proved or suspected to
      cause clinical manifestations of Lyme disease in humans, showed 10.5 and 2.2%
      combined prevalence in questing and engorged I. ricinus, respectively. In
      addition, two species of rickettsiae (R. helvetica and R. monacensis) were
      identified and reported with 14.5 and 24.8% overall prevalence in questing and in
      engorged ticks. The prevalence of F. tularensis in the ticks collected on two
      wild ungulate species (Capreolus capreolus and Cervus elaphus) was 5.7%. This
      work provided further data and broadened our knowledge on bacterial pathogens
      present in ticks in Northwest Italy.

PMID- 29189952
TI  - Immuno-proteomic analysis of Trichinella spiralis, T. pseudospiralis, and T.
      papuae extracts recognized by human T. spiralis-infected sera.
AB  - The present study explored potentially immunogenic proteins of the encapsulated
      (Trichinella spiralis) and non-encapsulated (T. pseudospiralis, T. papuae)
      species within the genus Trichinella. The somatic muscle larval extracts of each
      species were subjected to immunoblotting analysis using human T. spiralis
      infected serum samples. Fifteen reactive bands of all three species were selected
      for further protein identification by liquid chromatography-tandem mass
      spectrometry, and their possible functions were ascertained using the gene
      ontology. Our findings showed immunogenic protein patterns with molecular mass in
      the range of 33-67 kDa. Proteomic and bioinformatic analysis revealed a wide
      variety of functions of 17 identified proteins, which are associated with
      catalytic, binding, and structural activities. Most proteins were involved in
      cellular and metabolic processes that contribute in the invasion of host tissues
      and the larval molting processes. The parasite proteins were identified as actin
      5C, serine protease, deoxyribonuclease-2, and intermediate filament protein ifa
      1. This information may lead to alternative tools for selection of potential
      diagnostic protein markers or aid in the design of vaccine candidates for
      prevention and control of Trichinella infection.

PMID- 29189953
TI  - Answer to the Letter to the Editor of T. Kawada concerning "Risk factors for
      sciatica leading to hospitalization" by U. Euro et al. Eur Spine J (2017).
      doi:10.1007/s00586-017-5182-8.

PMID- 29189954
TI  - Synthesis, anti-angiogenic and DNA cleavage studies of novel N-(4-methyl-3-((4
      (pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)piperidine-4-carboxamide derivatives.
AB  - A series of novel N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2
      yl)amino)phenyl)piperidine-4-carboxamide derivatives 10(a-f), 12(a-c) and 14(a-c)
      were synthesized and characterized by FTIR, 1H-NMR, mass spectral and elemental
      analysis. The efficacy of these derivatives to inhibit in vivo angiogenesis was
      evaluated using chick chorioallantoic membrane (CAM) model and their DNA cleavage
      abilities were evaluated after incubating with calf thymus DNA followed by gel
      electrophoresis. These novel piperidine analogues efficiently blocked the
      formation of blood vessels in vivo in CAM model and exhibited differential
      migration and band intensities in DNA binding/cleavage assays. Among the tested
      compounds 10a, 10b, 10c, 12b, 14b and 14c showed significant anti-angiogenic and
      DNA cleavage activities compared to their respective controls and the other
      derivatives used in this study. These observations suggest that the presence of
      electron donating and withdrawing groups at positions 2, 3 and 4 of the phenyl
      ring of the side chain may determine their potency and as anticancer agents by
      exerting both anti-angiogenic and cytotoxic effects .

PMID- 29189955
TI  - A prospective assessment of outcomes following the use of autologous blood for
      the management of recurrent temporomandibular joint dislocation.
AB  - PURPOSE: The objective of the study was to compare results of treatment for
      chronic recurrent temporomandibular joint dislocation (CRTMD) by autologous blood
      injection (ABI) using two different methods of administration (combination intra-
      and peri-articular, and peri-articular alone). MATERIALS AND METHODS: Forty
      patients diagnosed with CRTMD were randomly divided into two groups of 20 each (A
      and B). Group A were treated by intra- and peri-articular blood injection, group
      B were treated by peri-articular injection alone. The follow-up was done at 1, 3,
      6, and 12 months. The study assessed presence of dislocations, pain (VAS, 0-10),
      interincisal mouth opening (IMO), and the presence of sound phenomena. The
      treatment was considered successful in patients without the persistence of CRTMD
      symptoms, as well as with a VAS of 0-1. RESULT: After 12 months, a beneficial
      therapeutic effect in group B was seen in 11 patients, while 16 patients from
      group A had a therapeutic effect. CONCLUSION: Intra- and peri-articular ABI is
      more effective than peri-articular blood application alone in the treatment of
      CRTMD, although the difference was not statistically significant.

PMID- 29189956
TI  - Changes of mitochondrial respiratory function during odontogenic differentiation
      of rat dental papilla cells.
AB  - Dental papilla cells (DPCs) belong to precursor cells differentiating to
      odontoblasts and play an important role in dentin formation and reproduction.
      This study aimed to explore the changes and and involvement of mitochondrial
      respiratory function during odontogenic differentiation. Primary DPCs were
      obtained from first molar dental papilla of neonatal rats and cultured in
      odontogenic medium for 7, 14, 21 days. DPCs, which expressed mesenchymal surface
      markers CD29, CD44 and CD90, had the capacity for self-renewal and multipotent
      differentiation. Odontoblastic induction increased mineralized matrix formation
      in a time-dependent manner, which was accompanied by elevated alkaline
      phosphatase (ALP), dentin sialophosphoprotein and dentin matrix protein 1
      expression at mRNA and protein levels. Notably, odontogenic medium led to an
      increase in adenosine-5'-triphosphate content and mitochondrial membrane
      potential, whereas a decrease in intercellular reactive oxygen species production
      and NAD+/NADH ratio. Furthermore, odontogenic differentiation was significantly
      suppressed by treatment with rotenone, an inhibitor of mitochondrial respiratory
      chain. These results demonstrate that enhanced mitochondrial function is crucial
      for odontogenic differentiation of DPCs.

PMID- 29189957
TI  - Actin genes and their expression in pacific white shrimp, Litopenaeus vannamei.
AB  - Actin is a multi-functional gene family that can be divided into muscle-type
      actins and non-muscle-type actins. In this study, 37 unigenes encoding actins
      were identified from RNA-Seq data of Pacific white shrimp, Litopenaeus vannamei.
      According to phylogenetic analysis, four and three cDNAs belong to cytoplasmic-
      and heart-type actins and were named LvActinCT and LvActinHT, respectively. 10
      cDNAs belong to the slow-type skeletal muscle actins, and 18 belong to the fast
      type skeletal muscle actins; they were designated LvActinSSK and LvActinFSK,
      respectively. Some muscle actin genes formed gene clusters in the genome.
      Multiple alternative transcription starts sites (ATSSs) were found for
      LvActinCT1. Based on the early developmental expression profile, almost all
      LvActins were highly expressed between the early limb bud and post-larval stages.
      Using LvActinSSK5 as probes, slow-type muscle was localized in pleopod muscle and
      superficial ventral muscle. We also found three actin genes that were down
      regulated in the hemocytes of white spot syndrome virus (WSSV)- and Vibrio
      parahaemolyticus-infected L. vannamei. This study provides valuable information
      on the actin gene structure of shrimp, furthers our understanding of the shrimp
      muscle system and helps us develop strategies for disease control and sustainable
      shrimp farming.

PMID- 29189958
TI  - Surgical treatment of spinal metastases from renal cell carcinoma-effects of
      preoperative embolization on intraoperative blood loss.
AB  - The objective of this paper is analyzing the effects of preoperative embolization
      on intraoperative blood loss in spinal surgery for renal cell carcinoma (RCC)
      metastasis and identifying factors contributing to an increased blood loss in the
      surgical procedure. A retrospective analysis was performed in patients who were
      treated in for spinal metastasis from RCC between 2011 and 2016. Factors analyzed
      were reduction of tumor blush, timing of embolization, selective vs.
      superselective approach, surgical factors, and tumor volume and localization.
      Parameters were statistically correlated with intraoperative blood loss
      (hemoglobin (Hg) decrease, blood loss in milliliters, number of transfused blood
      bags). Twenty-five patients with 34 surgical interventions were included.
      Seventeen cases were treated superselectively and 11 treated selectively. Mean
      perioperative blood loss was 2248 +/- 1833 ml. Higher blood loss was detected for
      vertebra replacement compared to percutaneous procedures (Hg decrease 4.22 vs.
      2.62, p < 0.05). Blood loss increased with increasing tumor volumes (0-50 ccm/50
      100 ccm/> 100 ccm) for Hg loss (3.29/3.64/4.24 mg/dl, NS), blood loss in
      milliliters (1291/2620/4971 ml, p < 0.001), and number of transfusions
      (1.2/3.4/7.0, p < 0.001). Stratifying by the grade of embolization, no
      significant differences were found between the groups (> 90%/90-75%/75-50%) for
      Hg loss, blood loss, or number of transfusions. Endovascular embolization for RCC
      metastasis of the spine is a safe procedure; however, in this cohort, patients
      undergoing embolization did not show a reduced blood loss in comparison to the
      non-embolized cohort. Additional factors contributing to an increased blood loss
      were tumor size and mode of surgery.

PMID- 29189959
TI  - Molecular dynamics calculation on structures, stabilities, mechanical properties,
      and energy density of CL-20/FOX-7 cocrystal explosives.
AB  - In this article, different CL-20/FOX-7 cocrystal models were established by the
      substitution method based on the molar ratios of CL-20:FOX-7. The structures and
      comprehensive properties, including mechanical properties, stabilities, and
      energy density, of different cocrystal models were obtained and compared with
      each other. The main aim was to estimate the influence of molar ratios on
      properties of cocrystal explosives. The molecular dynamics (MD) simulation
      results show that the cocrystal model with molar ratio 1:1 has the best
      mechanical properties and highest binding energy, so the CL-20/FOX-7 cocrystal
      model is more likely to form in 1:1 M ratio. The detonation parameters show that
      the cocrystal explosive exhibited preferable energy density and excellent
      detonation performance. In a word, the 1:1 cocrystal model has the best
      comprehensive properties, is very promising, and worth more theoretical
      investigations and experimental tests. This paper gives some original theories to
      better understand the cocrystal mechanism and provides some helpful guidance and
      useful instructions to help design CL-20 cocrystal explosives.

PMID- 29189960
TI  - A Review of the Landscape of Targeted Immunomodulatory Therapies for Non
      Infectious Uveitis.
AB  - Systemic immunomodulatory therapies are the principal means of managing non
      infectious uveitis. This review aims to explore the current landscape of systemic
      uveitis treatments, including biologic therapies and the advent of biosimilar
      therapies.

PMID- 29189961
TI  - Feasibility of endoscopic resection using bipolar snare for nonampullary duodenal
      tumours in familial adenomatous polyposis patients.
AB  - The management of duodenal and colorectal tumours is important in patients with
      familial adenomatous polyposis (FAP). Endoscopic resection (ER) should be
      carefully performed because the risk of complications during or after (ER) of
      nonampullary duodenal tumours is higher than that of stomach or colorectal
      lesions in general. Thus, we evaluated the feasibility of endoscopic resection
      using bipolar snare (ERB) for nonampullary duodenal tumours in FAP patients.
      Eleven FAP patients who underwent ERB for nonampullary duodenal tumours at our
      hospital between October 2013 and December 2016 were retrospectively analysed
      based on clinicopathological features. ER was generally indicated for
      endoscopically diagnosed tumours > 20 mm, biopsy-confirmed high-grade dysplasia
      or carcinomas > 10 mm, and multiple tumours. Nineteen endoscopic treatments were
      performed and 134 nonampullary duodenal tumours were resected. The median patient
      age at initial treatment was 40 years (range 20-64), and median size of the
      largest tumour in each procedure was 16 mm (range 9-40). Of the 101
      pathologically evaluated lesions, 10 tumours were high-grade tubular adenomas, 87
      were low-grade tubular adenomas, 1 was an adenocarcinoma, and 3 were non
      neoplastic mucosal polyps. No intraoperative or delayed perforations were
      observed. Melena was encountered in one patient and managed without emergent
      endoscopic intervention. ERB for nonampullary duodenal tumours of FAP patients is
      feasible and effective, even for large lesions with high-grade dysplasia. Long
      term outcomes of ERB, including local recurrence and prognosis, should be
      monitored.

PMID- 29189962
TI  - Metachronous colorectal cancer following segmental or extended colectomy in Lynch
      syndrome: a systematic review and meta-analysis.
AB  - Around 5% of colorectal cancers are due to mutations within DNA mismatch repair
      genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance
      with early onset of colorectal cancer at a mean age of 45 years. The mainstay of
      surgical management is either a segmental or extensive colectomy. Currently there
      is no unified agreement as to which management strategy is superior due to
      limited conclusive empirical evidence available. A systematic review and meta-
      analysis to evaluate the risk of metachronous colorectal cancer (MCC) and
      mortality in LS following segmental and extensive colectomy. A systematic review
      of the PubMed database was conducted. Studies were included/ excluded based on
      pre-specified criteria. To assess the risk of MCC and mortality attributed to
      segmental or extensive colectomies, relative risks (RR) were calculated and
      corresponding 95% confidence intervals (CI). Publication bias was investigated
      using funnel plots. Data about mortality, as well as patient ascertainment
      [Amsterdam criteria (AC), germline mutation (GM)] were also extracted.
      Statistical analysis was conducted using the R program (version 3.2.3). The
      literature search identified 85 studies. After further analysis ten studies were
      eligible for inclusion in data synthesis. Pooled data identified 1389 patients
      followed up for a mean of 100.7 months with a mean age of onset of 45.5 years of
      age. A total 1119 patients underwent segmental colectomies with an absolute risk
      of MCC in this group of 22.4% at the end of follow-up. The 270 patients who had
      extensive colectomies had a MCC absolute risk of 4.7% (0% in those with a
      panproctocolecomy). Segmental colectomy was significantly associated with an
      increased relative risk of MCC (RR = 5.12; 95% CI 2.88-9.11; Fig. 1), although no
      significant association with mortality was identified (RR = 1.65; 95% CI 0.90
      3.02). There was no statistically significant difference in the risk of MCC
      between AC and GM cohorts (p = 0.5, Chi-squared test). In LS, segmental colectomy
      results in a significant increased risk of developing MCC. Despite the choice of
      segmental or extensive colectomies having no statistically significant impact on
      mortality, the choice of initial surgical management can impact a patient's
      requirement for further surgery. An extensive colectomy can result in decreased
      need for further surgery; reduced hospital stays and associated costs. The
      significant difference in the risk of MCC, following segmental or extensive
      colectomies should be discussed with patients when deciding appropriate
      management. An individualised approach should be utilised, taking into account
      the patient's age, co-morbidities and genotype. In order to determine likely
      germline-specific effects, or a difference in survival, larger and more
      comprehensive studies are required.

PMID- 29189963
TI  - Multiple true-false items: a comparison of scoring algorithms.
AB  - Multiple true-false (MTF) items are a widely used supplement to the commonly used
      single-best answer (Type A) multiple choice format. However, an optimal scoring
      algorithm for MTF items has not yet been established, as existing studies yielded
      conflicting results. Therefore, this study analyzes two questions: What is the
      optimal scoring algorithm for MTF items regarding reliability, difficulty index
      and item discrimination? How do the psychometric characteristics of different
      scoring algorithms compare to those of Type A questions used in the same exams?
      We used data from 37 medical exams conducted in 2015 (998 MTF and 2163 Type A
      items overall). Using repeated measures analyses of variance (rANOVA), we
      compared reliability, difficulty and item discrimination of different scoring
      algorithms for MTF with four answer options and Type A. Scoring algorithms for
      MTF were dichotomous scoring (DS) and two partial credit scoring algorithms, PS50
      where examinees receive half a point if more than half of true/false ratings were
      marked correctly and one point if all were marked correctly, and PS1/n where
      examinees receive a quarter of a point for every correct true/false rating. The
      two partial scoring algorithms showed significantly higher reliabilities
      (alphaPS1/n = 0.75; alphaPS50 = 0.75; alphaDS = 0.70, alphaA = 0.72), which
      corresponds to fewer items needed for a reliability of 0.8 (nPS1/n = 74; nPS50 =
      75; nDS = 103, nA = 87), and higher discrimination indices (rPS1/n = 0.33; rPS50
      = 0.33; rDS = 0.30; rA = 0.28) than dichotomous scoring and Type A. Items scored
      with DS tend to be difficult (pDS = 0.50), whereas items scored with PS1/n become
      easy (pPS1/n = 0.82). PS50 and Type A cover the whole range, from easy to
      difficult items (pPS50 = 0.66; pA = 0.73). Partial credit scoring leads to better
      psychometric results than dichotomous scoring. PS50 covers the range from easy to
      difficult items better than PS1/n. Therefore, for scoring MTF, we suggest using
      PS50.

PMID- 29189964
TI  - The birth and death of curricula.

PMID- 29189965
TI  - Cerebral arterial and venous MRI abnormalities in MELAS.

PMID- 29189966
TI  - Management of adverse renal events related to alemtuzumab treatment in multiple
      sclerosis: a Belgian consensus.
AB  - Alemtuzumab is a humanized monoclonal antibody indicated for the treatment of
      adult patients with relapsing-remitting multiple sclerosis with active disease.
      Multiple sclerosis (MS) patients treated with alemtuzumab are at increased risk
      for autoimmune adverse events (thyroid disorders, immune thrombocytopenia, and
      renal disease). The use of alemtuzumab has been associated with the development
      of renal immune-mediated adverse events in 0.3% of patients in clinical trials in
      MS, which generally occurred within 39 months of the last administration. Both
      anti-GBM disease and membranous nephropathy have been associated with the use of
      alemtuzumab. Early detection is necessary to allow for early diagnosis and
      prevent adverse renal and patient outcomes. Through the implementation of the
      risk minimization measures, patients can be diagnosed, and treated if needed,
      early allowing for generally favorable outcomes. This important goal can be
      reached through health care professional and patient education, careful analysis
      of the monthly lab tests, and close collaboration between the patient,
      neurologist, and the nephrologist. This article presents the consensus of Belgian
      MS specialists and nephrologists on the practicalities of diagnosis, management,
      and treatment of alemtuzumab-associated renal adverse events based on good
      clinical practice.

PMID- 29189968
TI  - Detection of electrocardiographic changes in partial epileptic patients using
      local binary pattern based composite feature.
AB  - In this paper, we propose a novel method for detecting electrocardiographic (ECG)
      changes in partial epileptic patients using a composite feature set. At the core
      of our approach is a local binary pattern (LBP) based feature representation
      containing a set of statistical features derived from the distribution of LBPs of
      the ECG signal. In order to enhance the discriminating power, a set of
      statistical features are also extracted from the original ECG signal. The
      composite feature is then generated by combining the two homogeneous feature
      sets. The discriminating ability of the proposed composite feature is
      investigated using two different classifiers namely, support vector machine and a
      bagged ensemble of decision trees. Results from the experimental evaluation on
      the publicly available MIT-BIH ECG dataset demonstrate the superiority of the
      proposed features over conventional histogram based LBP features. Our results
      also show that the proposed approach provides better classification accuracy than
      methods existing in the literature for classification of normal and partial
      epileptic beats in ECG.

PMID- 29189967
TI  - Evaluation of a specialized oncology nursing supportive care intervention in
      newly diagnosed breast and colorectal cancer patients following surgery: a
      cluster randomized trial.
AB  - BACKGROUND: Better coordination of supportive services during the early phases of
      cancer care has been proposed to improve the care experience of patients. We
      conducted a randomized trial to test a community-based nurse-led coordination of
      care intervention in cancer patients. METHODS: Surgical practices were cluster
      randomized to a control group involving usual care practices or a standardized
      nursing intervention consisting of an in-person supportive care assessment with
      ongoing support to meet identified needs, including linkage to community
      services. Newly diagnosed breast and colorectal cancer patients within 7 days of
      cancer surgery were eligible. The primary outcome was the patient-reported
      outcome (PRO) of continuity of care (CCCQ) measured at 3 weeks. Secondary
      outcomes included unmet supportive care needs (SCNS), quality of life (EORTC QLQ
      C30), health resource utilization, and level of uncertainty with care trajectory
      (MUIS) at 3 and/or 8 weeks. RESULTS: A total of 121 breast and 72 colorectal
      patients were randomized through 28 surgical practices. There was a small
      improvement in the informational domain of continuity of care (difference 0.29 p
      = 0.05) and a trend to less emergency room use (15.8 vs 7.1%) (p = 0.07). There
      were no significant differences between groups on unmet need, quality of life, or
      uncertainty. CONCLUSION: We did not find substantial gaps in the PROs measured
      immediately following surgery for breast and colorectal cancer patients. The
      results of this study support a more targeted approach based on need and inform
      future research focused on improving navigation during the initial phases of
      cancer treatment. ClinicalTrials.gov Identifier: NCT00182234. SONICS
      Effectiveness of Specialist Oncology Nursing.

PMID- 29189969
TI  - The Annals of Surgical Oncology: An Oncology Journal for Surgeons.

PMID- 29189970
TI  - Climate change-induced heat risks for migrant populations working at brick kilns
      in India: a transdisciplinary approach.
AB  - During the summer of 2015, India was hit by a scorching heat wave that melted
      pavements in Delhi and caused thousands of deaths, mainly among the most
      marginalized populations. One such group facing growing heat risks from both
      occupational and meteorological causes are migrant brick kiln workers. This study
      evaluates both current heat risks and the potential future impacts of heat caused
      by climate change, for the people working at brick kilns in India. A case study
      of heat stress faced by people working at brick kilns near Chennai, India, is the
      anchor point around which a transdisciplinary approach was applied. Around
      Chennai, the situation is alarming since occupational heat exposure in the hot
      season from March to July is already at the upper limits of what humans can
      tolerate before risking serious impairment. The aim of the study was to identify
      new pathways for change and soft solutions by both reframing the problem and
      expanding the solution space being considered in order to improve the quality of
      life for the migrant populations at the brick kilns. Technical solutions
      evaluated include the use of sun-dried mud bricks and other locally "appropriate
      technologies" that could mitigate the worsening of climate change-induced heat.
      Socio-cultural solutions discussed for empowering the people who work at the
      brick kilns include participatory approaches such as open re-localization, and
      rights-based approaches including the environmental sustainability and the human
      rights-based approach framework. Our analysis suggests that an integrative,
      transdisciplinary approach could incorporate a more holistic range of technical
      and socio-culturally informed solutions in order to protect the health of people
      threatened by India's brick kiln industry.

PMID- 29189973
TI  - Somatosensory evoked potentials after decompressive craniectomy for traumatic
      brain injury.
AB  - Somatosensory evoked potentials (SSEPs) are used for neuroprognosis after severe
      traumatic brain injury (TBI). However decompressive craniectomy (DC), involving
      removal of a portion of the skull to alleviate elevated intracranial pressure, is
      associated with an increase in SSEP amplitude. Accordingly, SSEPs are not
      available for neuroprognosis over the hemisphere with DC. We aim to determine the
      degree to which SSEP amplitudes are increased in the absence of cranial bone.
      This will serve as a precursor for translation to clinically prognostic ranges.
      Intra-operative SSEPs were performed before and after bone flap replacement in 22
      patients with severe TBI. SSEP measurements were also performed in a comparison
      non-traumatic group undergoing craniotomy for tumor resection. N20/P25 amplitudes
      and central conduction time were measured with the bone flap in (BI) and out
      (BO). Linear regressions, adjusting for skull thickness and study arm, were
      performed to evaluate the contribution of bone presence to SSEP amplitudes.
      Latencies were not different between BO or BI trials in either group. Mean
      N20/P25 amplitudes recorded with BO were statistically different (p = 0.0001)
      from BI in both cohorts, showing an approximate doubling in BO amplitudes. For
      contralateral-ipsilateral montages r2 was 0.28 and for frontal pole montages r2
      was 0.62. Cortical SSEP amplitudes are influenced by the presence of cortical
      bone as is particularly evident in frontal pole montages. Larger, longitudinal
      trials to assess feasibility of neuroprognosis over the hemisphere with DC in
      severe TBI patients are warranted.

PMID- 29189972
TI  - Plasma lipopolysaccharide-binding protein and colorectal cancer risk: a nested
      case-control study in the Multiethnic Cohort.
AB  - BACKGROUND: Lipopolysaccharide (LPS), an endotoxin found on the outer cell wall
      of Gram-negative bacteria, increases inflammatory response signaling and may play
      a role in the pathogenesis of several adverse outcomes, including inflammatory
      bowel diseases, cardiovascular disease, and cancer. While LPS is hypothesized to
      be associated with colorectal carcinogenesis, there are relatively few human
      studies which have examined this association. METHODS: We examined the
      association between colorectal cancer (CRC) and plasma lipopolysaccharide-binding
      protein (LBP), a marker of LPS, in 1,638 participants (819 CRC cases and 819
      controls) matched on multiple factors, including age, sex, and race/ethnicity,
      from the Multiethnic Cohort study. Conditional logistic regression models were
      used to estimate the multivariable-adjusted odds ratios (OR) and 95% confidence
      intervals (95% CI). RESULTS: Compared to individuals whose LBP concentrations
      were in the lowest quartile, the ORs associated with second, third, and fourth
      quartiles were 1.23 (95% CI 0.91-1.67), 1.36 (95% CI 1.01-1.83), and 1.01 (95% CI
      0.73-1.39), respectively, (p trend = 0.66). No differences were observed by BMI,
      fiber intake, saturated fat intake, cancer site, or cancer stage. CONCLUSIONS:
      This study did not find an overall statistically significant association between
      LBP (as a marker of LPS exposure) and CRC. Further prospective studies with
      multiple LBP measurements are needed to validate current findings.

PMID- 29189974
TI  - Association of SIRT1 gene polymorphism and its expression for the risk of
      alcoholic fatty liver disease in the Han population.
AB  - OBJECTIVE: To investigate the associations between SIRT1 polymorphisms and their
      expression in patients with alcoholic fatty liver disease (AFLD). METHODS: A
      total of 268 heavy drinkers were divided into the AFLD group (n = 176) and
      alcoholic control (n = 92) and 237 light-/non-drinkers into the NAFLD (non-AFLD)
      group (n = 117) and healthy control (n = 120). The genotyping of SIRT1
      (rs33957861, rs11599176, rs12413112 and rs35689145) was detected by the Sequenom
      MassARRAY iPLEX test. The mRNA and protein expressions of SIRT1 were determined
      by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked
      immunosorbent assays (ELISA), respectively. RESULTS: SIRT1 gene rs33957861 and
      rs11599176 polymorphisms significantly reduce the risk of NAFLD and AFLD, while
      rs35689145 remarkably increases the risk. Haplotypes of AAAA (rs33957861
      rs11599176-rs12413112-rs35689145), AAAA, CAGA and CGAA can appreciably lower the
      presence of AFLD, but CAAG had an elevated AFLD risk. Besides, in the NAFLD and
      AFLD groups, a decreased BMI was found in the mutant genotype carriers of
      rs33957861, rs11599176 and rs12413112, but an increased BMI was observed in the
      rs35689145 mutant genotype carriers when compared to those with the wild-type
      homozygous genotype ones. Furthermore, rs33957861 C>T, rs11599176 A>G and BMI
      were independent risk factors of AFLD. There was no difference among four SNPs of
      SIRT1 and its mRNA and protein expressions in all groups. CONCLUSION: SIRT1
      polymorphisms and their expression were associated with the presence of AFLD, and
      there was a close relationship among four SNPs and BMI in AFLD patients, but no
      SNP was related to its expression.

PMID- 29189975
TI  - Trends in the medication reviews of community pharmacies in Japan: a nationwide
      retrospective study.
AB  - Background The trends in medication reviews made by community pharmacies in Japan
      are currently unknown. Objective We aimed to comprehensively describe the
      national trends in medication reviews in Japan's community pharmacies in the
      backdrop of the country's ageing population. Setting Community pharmacies in
      Japan. Methods We analysed national health insurance claims data for 2010-2015.
      These data were provided by the Ministry of Health, Labour and Welfare as part of
      the Survey of Medical Care Activities in Public Health Insurance. Main outcome
      measures The national trends in community pharmacy visits involving medicine
      dispensing and medication reviews that involve consultations with a physician.
      Results Among the 365 million pharmacy visits for 2010-2015, we identified
      373,429 medication reviews accompanied by consultations with a physician. The
      pharmacy visit rate per 1000 population increased from 427.2 in 2010 to 483.7 in
      2015. Medication reviews also increased from 407 per million pharmacy visits in
      2010 to 1445 in 2015. Among the 373,429 medication reviews during the study
      period, the prescription was changed through collaboration with a physician
      338,982 times (90.4%). The proportion of medication review acceptance increased
      from 80.6% in 2010 to 94.8% in 2015. The prescription change rate was higher
      among older patients than among younger ones. Conclusions Medication reviews by
      community pharmacists involving consultations with a physician increased in Japan
      from 2010 to 2015, as did prescription changes following these reviews.

PMID- 29189976
TI  - Validation of knowledge and adherence assessment tools among patients on warfarin
      therapy in a Saudi hospital anticoagulant clinic.
AB  - Background Although it can result in serious complications due to its narrow
      therapeutic index, warfarin is widely used in the treatment and prevention of
      thromboembolic disorders. However, patients' adherence and knowledge are
      determinants of therapeutic success. Objective We sought to validate instruments
      to provide a reliable means of identifying gaps in patient understanding and
      nonadherence to inform targeted pharmacists' interventions to improve these
      measures. Methods A cross-sectional survey was conducted. Patients' knowledge
      about warfarin was rated using an Arabic-language tool. Medication adherence was
      assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8). The
      international normalized ratio (INR) control was quantified by the Rosendaal
      Method. Setting At the Security Forces hospital anticoagulant clinic (ACC),
      Riyadh. Main outcome measure Validity of a Knowledge and adherence tool. Results
      Totally, 101 patients completed the questionnaires. Interestingly, the knowledge
      tool demonstrated good internal consistency (total Cronbach's alpha = 0.75) and
      significant concurrent validity with adherence levels. Fifty-two patients were
      classified as having unsatisfactory knowledge. Deficiency in knowledge was most
      obvious with respect to the consequences of missing a dose and when to seek
      immediate medical attention. The MMAS-8 had moderate reliability (Cronbach's
      alpha = 0.65); however, its concurrent validity with good INR control was not
      demonstrated. Conclusions This study revealed high prevalence of nonadherence and
      poor knowledge in the population visiting the ACC. Given that available knowledge
      and adherence tools seemed to have little validity in predicting clinical
      outcomes, structured tools should be designed, considering progression in
      clinical outcomes with future pharmacists' interventions.

PMID- 29189977
TI  - Efficacy and safety of atypical antipsychotics for behavioral symptoms of
      dementia among patients residing in long-term care.
AB  - Background There are limited options for the treatment of behavioral and
      psychological symptoms of dementia (BPSD). Objective Evaluate the efficacy and
      safety of using atypical antipsychotics for BPSD among patients residing in long
      term care. Setting Long term care community facility in the United States.
      Methods Retrospective observational study of patients residing in a long-term
      care facility with a diagnosis of dementia not trauma-induced with documented
      BPSD treated with an atypical antipsychotic for at least 2 weeks. Paper medical
      records were reviewed from January 1, 1990 until March 23, 2010. Main outcome
      measure Behavioral/psychological efficacy outcomes were documented beginning 2
      weeks after atypical antipsychotic therapy was initiated and safety outcomes were
      documented from the time of atypical antipsychotic initiation, until the last
      documentation available. Efficacy and safety outcomes were documented as part of
      routine clinical practice based on the responsible clinician. Results A total of
      85 distinct atypical antipsychotic treatment periods for 73 unique patients were
      included. Nearly 50% of patients continued atypical antipsychotic treatment for
      at least 1 year and 5.6% of treatments were discontinued due to an adverse event.
      Patients' behavioral/psychological outcomes improved for 52 (61%) treatments,
      remained stable for 17 (20%) treatments, and worsened for 16 (19%) treatments.
      Adverse events were reported by 57% of patients, with the most common adverse
      events being metabolic, fall related, and extrapyramidal symptoms. The odds ratio
      for an adverse event was 1.08 (p = 0.03) for every 90 day increase in duration of
      treatment. Conclusion In patients who reside in a long-term care setting,
      atypical antipsychotic treatment improved BPSD, but also increased the potential
      risk of adverse events.

PMID- 29189978
TI  - Disordered eating attitudes and emotional/behavioral adjustment in Greek
      adolescents.
AB  - PURPOSE: The aim of this study was to examine the relationship between disordered
      eating attitudes and emotional/behavioral adjustment in Greek adolescents as well
      as the moderating role of gender and body mass index (BMI) in this relationship.
      METHODS: Ninety adolescents, 11-18 years old, were assessed using anthropometric
      measurements; demographics, eating attitudes and level of emotional/behavioral
      adjustment were examined via self-reported questionnaires. RESULTS: Disordered
      eating attitudes were prevalent in 17.8% of the sample. A significant
      relationship was found between disordered eating attitudes and Youth Self-Report
      (YSR) anxiety score (r = .22, p < .05). Gender significantly moderated the
      relationship between YSR anxiety symptoms and Eating Attitudes Test (EAT) scores
      (b = .59, p = .01) and this effect held true for the EAT bulimia subscale (b =
      .20, p = .03), but not for the dieting or the oral control subscales. Contrary to
      our hypothesis, BMI did not moderate the relationship between EAT and YSR anxiety
      sub-scores (b = .13, p > .05). CONCLUSION: Girls with elevated anxiety levels
      appear to be at risk for exhibiting disordered eating attitudes, especially
      bulimic behaviors. This finding highlights the importance of developing gender
      based preventive interventions tailored to these specific emotional/behavioral
      aspects. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

PMID- 29189979
TI  - Comparison of biophysical properties characterized for microtissues cultured
      using microencapsulation and liquid crystal based 3D cell culture techniques.
AB  - Growing three dimensional (3D) cells is an emerging research in tissue
      engineering. Biophysical properties of the 3D cells regulate the cells growth,
      drug diffusion dynamics and gene expressions. Scaffold based or scaffoldless
      techniques for 3D cell cultures are rarely being compared in terms of the
      physical features of the microtissues produced. The biophysical properties of the
      microtissues cultured using scaffold based microencapsulation by flicking and
      scaffoldless liquid crystal (LC) based techniques were characterized. Flicking
      technique produced high yield and highly reproducible microtissues of
      keratinocyte cell lines in alginate microcapsules at approximately 350 +/- 12
      pieces per culture. However, microtissues grown on the LC substrates yielded at
      lower quantity of 58 +/- 21 pieces per culture. The sizes of the microtissues
      produced using alginate microcapsules and LC substrates were 250 +/- 25 MUm and
      141 +/- 70 MUm, respectively. In both techniques, cells remodeled into
      microtissues via different growth phases and showed good integrity of cells in
      field-emission scanning microscopy (FE-SEM). Microencapsulation packed the cells
      in alginate scaffolds of polysaccharides with limited spaces for motility.
      Whereas, LC substrates allowed the cells to migrate and self-stacking into
      multilayered structures as revealed by the nuclei stainings. The cells cultured
      using both techniques were found viable based on the live and dead cell
      stainings. Stained histological sections showed that both techniques produced
      cell models that closely replicate the intrinsic physiological conditions.
      Alginate microcapsulation and LC based techniques produced microtissues
      containing similar bio-macromolecules but they did not alter the main absorption
      bands of microtissues as revealed by the Fourier transform infrared spectroscopy.
      Cell growth, structural organization, morphology and surface structures for 3D
      microtissues cultured using both techniques appeared to be different and might be
      suitable for different applications.

PMID- 29189980
TI  - Patients with type 1 diabetes mellitus have impaired IL-1beta production in
      response to Mycobacterium tuberculosis.
AB  - Patients with diabetes mellitus have an increased risk of developing
      tuberculosis. Although the underlying mechanism is unclear, evidence suggests a
      role for chronic hyperglycaemia. We examined the influence of hyperglycaemia on
      Mycobacterium tuberculosis-induced cytokine responses in patients with type 1
      diabetes mellitus (T1D). Peripheral blood mononuclear cells (PBMCs) from 24 male
      T1D patients with sub-optimal glucose control [HbA1c > 7.0% (53 mmol/L)] and from
      24 age-matched male healthy controls were stimulated with M. tuberculosis lysate.
      Cytokine analysis, assessment of aerobic glycolysis, receptor recognition and
      serum cross-over experiments were performed to explore the mechanistic
      differences. PBMCs from T1D patients produced less bioactive interleukin (IL)
      1beta in response to M. tuberculosis. IL-6 and interferon (IFN)-gamma production
      trended towards a decrease, whilst other cytokines such as tumour necrosis factor
      (TNF)-alpha, IL-17 and IL-1Ra were normal. The decrease in cytokine production
      was not correlated to HbA1c or plasma glucose levels. Cross-over serum
      experiments did not alter the cytokine profile of T1D or control patients,
      arguing for an intrinsic cellular defect. Cellular metabolism and the expression
      of M. tuberculosis-related pattern recognition receptors (PRRs) such as TLR2,
      TLR4 and NOD2 did not differ between T1D patients and healthy controls. Compared
      to matched controls, T1D patients have a reduced capacity to produce pro
      inflammatory cytokines in response to M. tuberculosis. The impaired IL-1beta
      production in T1D patients may contribute to the increased susceptibility to
      tuberculosis. This effect appears not to be related to prevailing glucose levels
      but to an intrinsic cellular deficit.

PMID- 29189981
TI  - Healthcare associated bloodstream infections in Polish hospitals: prevalence,
      epidemiology and microbiology-summary data from the ECDC Point Prevalence Survey
      of Healthcare Associated Infections 2012-2015.
AB  - Aggregated data from the Polish Point Prevalence Survey of Healthcare Associated
      Infections and Antimicrobial Use (PPS HAI&AU) collected between 2012 and 2015
      were used to describe the epidemiology of healthcare associated bloodstream
      infections (BSI) in Polish hospitals, in order to assess the rationale for
      introducing a BSI surveillance programme in our country and analyse selected risk
      factors. Data were collected according to the ECDC PPS HAI&AU protocol. Within
      four years, records for 71,039 patients were collected in 36 (2012), 32 (2013),
      112 (2014), and 158 (2015) hospitals; representativeness was evaluated as good in
      2012-2013, and excellent from 2014. HAI was found in 4,258 of these patients;
      laboratory confirmed BSI, including catheter related infections (CRI), and
      neonatal BSI accounted for 7.7% (329 cases). A representative control group was
      selected during a random selection process. Out of 329 cases of BSI, 48.9% were
      associated with vascular access, and 70.8% of them met the criteria of (CRI). The
      most frequently isolated microorganisms were Staphylococci with 150 isolates
      (45.6%). Most of them were coagulase-negative (64.4%) that usually caused CRI.
      Out of 53 S. aureus isolates 24.5% were methicillin-resistant. Enterobacteriaceae
      were responsible for 31.3% of BSI (n = 103), 50.0% of them were resistant to
      third generation cephalosporins and 6 (5.8%) to carbapenems. Since little is
      known about the epidemiology of BSI in Poland, introduction of a countrywide
      surveillance programme based on incidence is justified, in order to create
      national prevention initiatives based on local epidemiology, as well as bundle
      focusing on prevention of CRI.

PMID- 29189982
TI  - How Infertility Patients and Providers View and Confront Religious and Spiritual
      Issues.
AB  - Questions arise concerning whether and how religion affects infertility treatment
      decisions. Thirty-seven infertility providers and patients were interviewed.
      Patients confront religious, spiritual, and metaphysical issues coping with
      treatment failures and religious opposition from clergy and others. Religion can
      provide meaning and support, but poses questions and objections that patients may
      try to avoid or negotiate-e.g., concealing treatment or changing clergy.
      Differences exist within and between religions. Whether and how much providers
      discuss these issues with patients varies. These data, the first to examine
      several key aspects of how infertility providers and patients confront
      religious/spiritual issues, have important implications for practice, research,
      guidelines, and education.

PMID- 29189983
TI  - Patient Appreciation of Student Chaplain Visits During Their Hospitalization.
AB  - Spiritual care is associated with improved health outcomes and higher patient
      satisfaction. However, chaplains often cover many hospital units and thus may not
      be able to serve all patients. Involving student chaplains in patient spiritual
      care may allow for more patients to experience the support of spiritual care. In
      this study, we surveyed 93 patients hospitalized on general medical units at a
      tertiary care center who were visited by nine student chaplain summer interns.
      The results indicated that the majority of patients appreciated student chaplain
      visits and these encounters may have positively influenced their overall hospital
      experience. Thus, student chaplains could be a way to extend valuable spiritual
      care in settings where chaplaincy staff shortages preclude access.

PMID- 29189984
TI  - The role of resveratrol on skeletal muscle cell differentiation and myotube
      hypertrophy during glucose restriction.
AB  - Glucose restriction (GR) impairs muscle cell differentiation and evokes myotube
      atrophy. Resveratrol treatment in skeletal muscle cells improves inflammatory
      induced reductions in skeletal muscle cell differentiation. We therefore
      hypothesised that resveratrol treatment would improve muscle cell differentiation
      and myotube hypertrophy in differentiating C2C12 myoblasts and mature myotubes
      during GR. Glucose restriction at 0.6 g/L (3.3 mM) blocked differentiation and
      myotube hypertrophy versus high-glucose (4.5 g/L or 25 mM) differentiation media
      (DM) conditions universally used for myoblast culture. Resveratrol (10 uM)
      treatment increased SIRT1 phosphorylation in DM conditions, yet did not improve
      differentiation when administered to differentiating myoblasts in GR conditions.
      Resveratrol did evoke increases in hypertrophy of mature myotubes under DM
      conditions with corresponding elevated Igf-I and Myhc7 gene expression, coding
      for the 'slow' type I MYHC protein isoform. Inhibition of SIRT1 via EX-527
      administration (100 nM) also reduced myotube diameter and area in DM conditions
      and resulted in lower gene expression of Myhc 1, 2 and 4 coding for
      'intermediate' and 'faster' IIx, IIa and IIb protein isoforms, respectively.
      Resveratrol treatment did not appear to modulate phosphorylation of energy
      sensing protein AMPK or protein translation initiator P70S6K. Importantly, in
      mature myotubes, resveratrol treatment was able to ameliorate reduced myotube
      growth in GR conditions over an acute 24-h period, but not over 48-72 h. Overall,
      resveratrol evoked myotube hypertrophy in DM conditions while favouring 'slower'
      Myhc gene expression and acutely ameliorated impaired myotube growth observed
      during glucose restriction.

PMID- 29189986
TI  - 1H, 13C, and 15N chemical shift assignments of a G-quadruplex forming sequence
      within the KRAS proto-oncogene promoter region.
AB  - Single stranded guanine rich DNA (or RNA) sequences adopt noncanonical secondary
      structures called G-quadruplexes (G4). Functionally, quadruplexes control gene
      transcription and regulate activities such as replication, gene recombination or
      alternative splicing. Hence they are potential targets for cancer, neuronal, and
      viral related diseases. KRAS is one of the most mutated oncogenes in the genome
      of cancer cells and contains a nuclease hypersensitive element (NHE) sequence
      capable of forming G-quadruplexes via its six runs of guanines. In our work, we
      are interested in the NMR structure of the major G4 scaffold formed in the KRAS
      NHE region with a mutated sequence of 22 residues. Here, we report 1H, 13C and
      15N chemical shift assignments the G4 formed within KRAS22RT sequence.

PMID- 29189985
TI  - Evaluation of the effect of the new methoxy-stilbenes on expression of receptors
      and enzymes involved in estrogen synthesis in cancer breast cells.
AB  - Our previous study showed that the new synthetic methoxy-stilbenes, 3,4,2'
      trimethoxy-trans-stilbene (3MS), 3,4,2',4'-tetramethoxy-trans-stilbene (4MS), and
      3,4,2',4',6'-pentamethoxy-trans-stilbene (5MS), modulate the constitutive
      expression of enzymes and receptors involved in estrogen metabolism in breast
      immortalized epithelial MCF10 cells. In this study, we evaluated the effect of
      3MS, 4MS, and 5MS in comparison to resveratrol activity in MCF7 estrogen
      dependent and MDA-MB-231 estrogen-independent breast cancer cell lines. 3MS
      similarly to resveratrol reduced the expression of estrogen receptor alpha in
      MCF7 cells. However, in these cells, 5MS reduced the most CYP19, the gene
      encoding aromatase, at mRNA transcript level. In contrast, in the MDA-MB-231
      cells, the most efficient inhibitor of CYP19 expression was 3MS, reducing the
      level of its protein by ~ 25%. This stilbene also inhibited the aromatase
      activity in a recombinant protein system with IC50 value ~ 85 uM. Treatment with
      the methoxy-stilbenes reduced the level of estradiol in culture medium. The most
      significant reduction was exerted by 3MS. None of the tested stilbenes including
      resveratrol changed significantly the expression of AhR, although CYP1A1 protein
      level was slightly reduced in MDA-MB-231 cells, while CYP1B1 expression was
      increased in these cells as a result of treatment with 3MS, but only at the
      transcript level. Overall, these results show weak or moderate effect of the new
      methoxy-stilbenes on the expression of key proteins involved in estrogens
      metabolism in cancer breast cells. However, the reduced CYP19 expression and
      activity upon 3MS treatment in metastatic MDA-MB-231 cells require the further
      studies.

PMID- 29189987
TI  - Lessons Learned from the Young Breast Cancer Survivorship Network.
AB  - The Young Breast Cancer Survivors Network (Network) is an academic and community
      based partnership dedicated to education, support, and networking. The Network
      used a multi-pronged approach via monthly support and networking, annual
      education seminars, website networking, and individual survivor consultation.
      Formative and summative evaluations were conducted using group survey and
      individual survivor interviews for monthly gatherings, annual education meetings,
      and individual consultation. Google Analytics was applied to evaluate website
      use. The Network began with 4 initial partnerships and grew to 38 in the period
      from 2011 to 2017. During this 5-year period, 5 annual meetings (598 attendees),
      23 support and networking meetings (373), and 115 individual survivor
      consultations were conducted. The Network website had nearly 12,000 individual
      users and more than 25,000 page views. Lessons learned include active community
      engagement, survivor empowerment, capacity building, social media outreach, and
      network sustainability. The 5-year experiences with the Network demonstrated that
      a regional program dedicated to the education, support, networking, and needs of
      young breast cancer survivors and their families can become a vital part of
      cancer survivorship services in a community. Strong community support,
      engagement, and encouragement were vital components to sustain the program.

PMID- 29189989
TI  - Correction to: Synthesis, characterization and in vitro antimicrobial activity of
      novel fused pyrazolo[3,4-c]pyridazine, pyrazolo[3,4-d]pyrimidine, thieno[3,2-c]
      pyrazole and pyrazolo[3',4':4,5]thieno[2,3-d]pyrimidine derivatives.
AB  - After the publication of this work [1] it was noticed that on page 3 of the
      article beginning in the paragraph-'Hydrazide 14 is used as a key producer...'
      the compound-"Not ethyl-N'-5-amino-1,3-diphenyl-1H-thieno[3,2-c]pyrazole-6
      carbonylformohydrazonate" should be deleted. Also on page 10 of the PDF beginning
      in paragraph-'Synthesis of 5-amino-...' the compound-"Not ethyl-N'-5-amino-1,3
      diphenyl-1H-thieno[3,2-c]pyrazole-6-carbonylformohydrazonate" should be deleted.
      We apologise for these errors.

PMID- 29189988
TI  - Predictors of self-reported health-related quality of life according to the EQ-5D
      Y in chronically ill children and adolescents with asthma, diabetes, and juvenile
      arthritis: longitudinal results.
AB  - PURPOSE: Health-related quality of life (HRQoL) is an important patient-reported
      outcome in clinical and health research. The EQ-5D-Y assesses child and
      adolescent HRQoL by five items on mobility, self-care, usual activities,
      pain/discomfort, and anxiety/depression as well as a visual analogue scale (VAS)
      on the current health state. This study investigates predictors of self-reported
      HRQoL according to the EQ-5D-Y in chronically ill children and adolescents using
      longitudinal data. METHODS: Data from the German Kids-CAT study on children and
      adolescents with asthma, diabetes, and juvenile arthritis gathered over a period
      of six months were analyzed (n = 310; 7-17 years old; 48% female). Self-, parent
      , and pediatrician-reported data were collected from June 2013 to October 2014.
      Generalized linear mixed models and linear mixed models served to examine effects
      of socio-demographic as well as disease- and health-specific predictors on the
      items as well as on the VAS of the EQ-5D-Y. RESULTS: Ceiling effects for the EQ
      5D-Y indicated low burden of disease in the analyzed sample. Longitudinal
      analyses revealed associations between less health complaints and better HRQoL
      for all investigated HRQoL domains. Further, age- and gender-specific effects,
      and associations of better disease control, longer duration of the disease and
      less mental health problems with better HRQoL were found. CONCLUSIONS: Subjective
      health complaints and mental health problems should be considered in the care of
      children and adolescents with asthma, diabetes, and juvenile arthritis. Future
      research should suggest administering the items of the EQ-5D-Y with five instead
      of three response options, and investigate HRQoL over a longer period.

PMID- 29189990
TI  - Importance of background values in assessing the impact of heavy metals in river
      ecosystems: case study of Tisza River, Serbia.
AB  - The main objective of this paper is to evaluate how a choice of different
      background values may affect assessing the anthropogenic heavy metal pollution in
      sediments from Tisza River (Serbia). The second objective of this paper is to
      underline significance of using geochemical background values when establishing
      quality criteria for sediment. Enrichment factor (EF), geoaccumulation index (I
      geo), pollution load index (PLI), and potential ecological risk index (PERI) were
      calculated using different background values. Three geochemical (average metal
      concentrations in continental crust, average metal concentrations in shale, and
      average metal concentrations in non-contaminated core sediment samples) and two
      statistical methods (delineation method and principal component analyses) were
      used for calculating background values. It can be concluded that obtained
      information of pollution status can be more dependent on the use of background
      values than the index/factor chosen. The best option to assess the potential
      river sediment contamination is to compare obtained concentrations of analyzed
      elements with concentrations of mineralogically and texturally comparable,
      uncontaminated core sediment samples. Geochemical background values should be
      taken into account when establishing quality criteria for soils, sediments, and
      waters. Due to complexity of the local lithology, it is recommended that
      environmental monitoring and assessment include selection of an appropriate
      background values to gain understanding of the geochemistry and potential source
      of pollution in a given environment.

PMID- 29189991
TI  - CSN5 Promotes Hepatocellular Carcinoma Progression by SCARA5 Inhibition Through
      Suppressing beta-Catenin Ubiquitination.
AB  - BACKGROUND: Increasing evidence has suggested that E3 Ubiquitin Ligase CSN5 is a
      newly characterized oncogene involved in various types of cancer. Scavenger
      receptor class A member 5 (SCARA5) is an important regulator of biological
      processes in cancer cells. However, the roles and relationship of CSN5 and SCARA5
      in hepatocellular carcinoma (HCC) remain unclear. METHODS: We used RT-PCR,
      Western blot, and immunohistochemistry to measure CSN5 and SCARA5 expression in
      HCC tissues and corresponding non-tumor tissues. The CSN5 gene was overexpressed
      or silenced with lentiviral vectors in HCC cells. Cell proliferation was measured
      using CCK8 assay. And, the cell migration and invasion were analyzed by transwell
      assay. RESULTS: We found that the expressions of CSN5 and SCARA5 are inversely
      correlated in HCC tissues, and CSN5 expression levels were negatively correlated
      with the levels of SCARA5 in various HCC cells. Furthermore, we found that high
      level of CSN5 expression correlated closely with tumor TNM stage, tumor size, and
      venous metastasis, but low level of SCARA5 expression correlated closely with
      tumor TNM stage, tumor size, and venous metastasis. Additionally, survival of
      patients with lower expression of CNS5 was significantly better than that of
      higher expression group, but the survival of patients with higher expression of
      SCARA5 was significantly better than that of lower expression group. Moreover,
      knockdown of CSN5 increased SCARA5 expression and inhibited the proliferation and
      metastasis of HCC cells in vitro and in vivo. Finally, we found that CSN5
      regulated SCARA5 expression by modulating beta-catenin. Mechanistically, our
      results indicate that CSN5 can decrease beta-catenin ubiquitination to enhance
      the protein expression of SCARA5 in HCC cells. CONCLUSIONS: Our data identified
      CSN5 as a critical oncoprotein involved in progression of HCC cells, which could
      serve as a potential therapeutic target in HCC patients.

PMID- 29189992
TI  - Effects of exergaming on cardiovascular risk factors and adipokine levels in
      women.
AB  - The aim of this study was to examine the effects of exergaming on the
      cardiovascular risk factors and adipokine levels of women engaged in the music
      video game Just Dance using the Xbox 360 Kinect console. Triglycerides, total
      cholesterol, HDL, LDL, FFA, CRP, TNF-alpha, Il-1beta, IL-6, leptin, and resistin
      were measured in sedentary women before and 1 month after the practice of
      exergaming. We also evaluated anthropometric parameters. Our results indicate
      that total serum cholesterol, triglycerides, and LDL were reduced by 64, 29, and
      12%, respectively. HDL levels were not altered in the conditions of this study. A
      significant decrease was also found in the concentrations of TNF-alpha (57%), CRP
      (84.7%), resistin (68.4%), leptin (35%), FFA (90%), body mass index (10.5%), fat
      percentage (10.9%), weight (5.6%), abdominal circumference (2.3%), hip
      circumference (2.5%), and waist circumference (1.9%) after the training period.
      We concluded that exergaming was successful in reducing body fat, serum adipokine
      levels, and lipid profiles, thus reducing cardiovascular risks for women.

PMID- 29189993
TI  - Barriers to Physical and Mental Health: Understanding the Intersecting Needs of
      Cambodian and Latino Residents in Urban Communities.
AB  - A community needs assessment was conducted to explore barriers and facilitators
      to good physical and mental health among Cambodian and Latino residents in an
      urban community in Southern California. Thirty-six Cambodians and 29 Latinos
      completed the interviewer-facilitated survey administered door-to-door, and
      another 20 Cambodian and 18 Latino residents participated in focus groups. Crime,
      limited knowledge of positive health behaviors, lack of access to affordable
      healthcare, and lack of access to safe spaces for recreational activities were
      identified as threats to good health. Participant recommendations to support
      health in the community included increasing police presence to improve safety and
      reduce violence, and increasing opportunities/locations for physical exercise.
      While differences between Cambodian and Latino residents exist, the identified
      threats and suggested improvements were primarily associated with environmental
      factors, highlighting the need for systems level approaches that recognize the
      relationship between community context and health.

PMID- 29189994
TI  - Impact of a Usual Source of Care on Health Care Use, Spending, and Quality Among
      Adults With Mental Health Conditions.
AB  - Physical comorbidities associated with mental health conditions contribute to
      high health care costs. This study examined the impact of having a usual source
      of care (USC) for physical health on health care utilization, spending, and
      quality for adults with a mental health condition using Medicaid administrative
      data. Having a USC decreased the probability of inpatient admissions and
      readmissions. It decreased expenditures on emergency department visits for
      physical health, 30-day readmissions, and behavioral health inpatient admissions.
      It also had a positive effect on several quality measures. Results underscore the
      importance of a USC for physical health and integrated care for adults with
      mental health conditions.

PMID- 29189996
TI  - Zinc Sulphate Mediates the Stimulation of Cell Proliferation of Rat Adipose
      Tissue-Derived Mesenchymal Stem Cells Under High Intensity of EMF Exposure.
AB  - Unlike the role of mesenchymal stem cells (MSCs) in regenerative medicine, their
      application in cell therapy can be complicated by factors such as a reduction in
      the proliferation potential, senescent tendency of MSCs to expand, and an age
      dependent decline in their number and functions. It was shown that there is an
      association between exposure to electromagnetic fields (EMFs) and response to
      stress, cell proliferation, aging, and cell death. Furthermore, the zinc ion, as
      an essential trace element, was reported to be involved in the regulation of the
      growth and cell proliferation. In this report, ratadipose tissue-derived
      mesenchymal stem cells (rADSCs) were randomly divided into four groups-group I
      (control without any ZnSO4 and EMF); group II (ZnSO4 treatment without EMF
      exposed); group III (EMF exposed without ZnSO4); and group IV (EMF exposed with
      ZnSO4)-to evaluate whether 0.14 MUg/ml Zinc sulfate (ZnSO4) could affect cell
      proliferation of rADSCs under extremely low frequency-electromagnetic field (ELF
      EMF). The methyl thiazoltetrazolium (MTT) method was used to determine the cell
      proliferation of rADSCs following exposure to ELF-EMF in the presence of ZnSO4.
      The immunocytochemistry method as well as flow-cytometry was used to identify the
      cell surface markers. Next, oil red O, alizarin red, toluidine blue, and cresyl
      violet staining was done to evaluate the adipogenic, osteogenic, chondrogenic,
      and neurogenic differentiation of rADSCs as the pluripotent capacity of rADSCs,
      respectively. The results showed that an exposure to ELF-EMF caused a decrease in
      the proliferation of rADSCs. However, the ZnSO4 supplementation significantly
      increased the cell proliferation of ELF-EMF-exposed rADSCs. In addition, in the
      presence of 0.14 MUg/ml ZnSO4, rADSCs appeared to be growing faster than the
      control group and ZnSO4 significantly decreased the doubling time of ELF-EMF
      exposed rADSCs. It seems that ZnSO4 would be a good element to induce the cell
      proliferation of ELF-EMF-exposed rADSCs.

PMID- 29189995
TI  - Acetyl-L-Carnitine Attenuates Arsenic-Induced Oxidative Stress and Hippocampal
      Mitochondrial Dysfunction.
AB  - Augmentation of mitochondrial oxidative stress through activating a series of
      deadly events has implicated as the main culprit of arsenic toxicity and
      therapeutic approaches based on improving mitochondrial function hold a great
      promise for attenuating the arsenic-induced toxicity. Acetyl-L-carnitine (ALC)
      through balancing the coenzyme A (CoA)/acyl-CoA ratio plays an important role in
      mitochondrial metabolism and thereby can help protect hippocampal neurons from
      oxidative damage. In the present study, we aimed to explore the effect of arsenic
      interactions on the mitochondrial function in the hippocampus of rats. Rats were
      randomly divided into five groups of control (distilled water), sodium arsenite
      (NaAsO2, 20 mg/kg), and co-treatment of NaAsO2 with various doses of ALC in three
      groups (100, 200, 300 mg/kg) and were treated orally for 21 consecutive days. Our
      results point out that arsenic exposure caused oxidative stress in rats'
      hippocampus, which led to the reactive oxygen species (ROS) generation,
      mitochondrial swelling, the collapse of the mitochondrial membrane potential, and
      release of cytochrome c. It also altered Bcl-2/Bax expression ratio and increased
      caspase-3 and caspase-9 activities. Furthermore, arsenic exposure via activation
      of NF-kappaB and microglia increased inflammation. ALC could concentration
      dependently counteract the arsenic-induced oxidative stress, modulate the
      antioxidant defense capacity, and improve mitochondrial functions. In addition,
      ALC decreased the expression of both death-associated proteins and of
      inflammatory markers. These findings indicate that ALC improved the arsenic
      induced hippocampal mitochondrial dysfunction which underlines the importance of
      ALC in providing a possible therapeutic strategy for the prevention of arsenic
      induced neurodegeneration.

PMID- 29189997
TI  - A new species of Uniclypea Boucek, 1976 (Hymenoptera: Pteromalidae) parasitic on
      Apoderus tranquebaricus Fabricius (Coleoptera: Attelabidae) from India with notes
      on biology.
AB  - One new species of parasitic wasp, Uniclypea similis n. sp. (Hymenoptera:
      Pteromalidae), reared from the leaf knots constructed by Apoderus tranquebaricus
      Fabricius (Coleoptera: Attelabidae) on the host plant Grewia abutilifolia Vent.
      ex Juss. is described and illustrated. The characteristic features of the new
      species are: post-marginal vein 2.3* stigmal vein, metasoma length 4.3* its width
      and costal cell 1.47* marginal vein. To my knowledge, the male of a species of
      Uniclypea is described and illustrated for the first time.

PMID- 29190000
TI  - A genome-wide DNA methylation analysis in peripheral blood from patients
      identifies risk loci associated with Graves' orbitopathy.
AB  - OBJECTIVE: Graves' orbitopathy (GO) is an inflammatory orbital disease of
      autoimmune origin with the potential to cause severe functional and psychosocial
      effects. The pathogenesis has not been fully elucidated. We investigated whether
      DNA methylation was associated with GO incidence in Chinese patients. MATERIALS
      AND METHODS: Six GO patients and six age-matched controls were recruited, and
      genome-wide DNA methylation patterns were analyzed in their peripheral blood. t
      tests were performed to determine differential methylated sites in genomic
      regions and the univariable logistic regression analyses was performed to
      evaluate their risk with GO incidence. Cluster analysis and principal component
      analysis (PCA) were performed to determine the effects of the extracted
      differentially methylated sites. RESULTS: One hundred and forty-eight
      differentially methylated sites were identified, including CD14 (fold change =
      4.31, p = 0.005), IL17RE (fold change = 2.128, p = 0.005), and DRD4 (fold change
      = 0.25, p = 0.004), and were supported by cluster and PCA analyses. Univariable
      logistic regression analyses showed that the methylation patterns at 12 loci were
      associated with GO incidence. The relative risk per 1% decrease in methylation at
      ZCCHC6 and GLI3 was 0.15 (95% CI 0.03-0.91; p = 0.039) and 0.65 (95% CI 0.42
      0.98; p = 0.042), respectively. Pearson correlation analyses demonstrated that
      methylation levels at IL17RE were positively associated with Clinical Activity
      Score (CAS) (r = 0.967, p < 0.05). CONCLUSIONS: Our results demonstrate that
      differential methylation levels at analyzed sites (genes) may be risk markers of
      GO. DNA methylation analysis could provide new insights into understanding the
      disease and provide new treatment strategies for GO in Chinese patients.

PMID- 29189999
TI  - NAFLD/NASH in patients with type 2 diabetes and related treatment options.
AB  - Type 2 diabetes may reduce life expectancy and patients' quality of life due to
      its micro- and macro-vascular complications and to the higher risk of several
      types of cancer. An emerging important factor is represented by the hepatic
      involvement; it is recognized that excessive hepatic fat accumulation represents
      a typical feature of diabetic patients and that it also plays an important
      pathogenic role. It is now evident that non-alcoholic fatty liver disease
      (NAFLD), generally perceived as a benign condition, may have on the contrary an
      important deleterious impact for diabetic patients increasing the risk to develop
      cardiovascular complications but also serious hepatic diseases, in particular non
      alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma.
      Lifestyle intervention, bariatric surgery and several drug therapies have now
      accumulated evidence of efficacy in treating NASH. On the other hand, their
      durability and safety in the long-term is yet to be proven and their use may be
      sometimes associated with side effects or higher risk of adverse events limiting
      the regular administration or contraindicating it. Professional health care
      providers, building awareness about the importance of these hepatic
      complications, should put more efforts in primary prevention using a behavioral
      therapy needing a multidisciplinary approach, in secondary prevention applying on
      a regular basis in the clinical setting available predictive algorithms to
      identify the patients at higher cardiovascular and hepatologic risk, and in
      tertiary prevention treating, when not contraindicated, the diabetic patients
      preferentially with drugs with proven benefit on NAFLD/NASH.

PMID- 29190001
TI  - Richness and Composition of Ground-dwelling Ants in Tropical Rainforest and
      Surrounding Landscapes in the Colombian Inter-Andean Valley.
AB  - Tropical rainforests are characterized by having high structural complexity,
      stratification, and species diversity. In Colombia, tropical rainforests are
      critically endangered with only 24% of their area remaining. Forest fragments are
      often valued based on the presence of vertebrate taxa despite that small habitat
      remnants may still harbor diverse invertebrate communities. We surveyed the ant
      fauna associated with rainforest fragments and their surrounding landscape
      elements (including mature forests, flooded forests, gallery forests, live
      fences, and pastures) in the Magdalena River watershed. Pitfall traps and litter
      samples were used to estimate ant richness and diversity, and to compare ant
      composition among landscape elements. We found 135 species from 42 genera,
      representing 16% of the species and 43% of the genera known for Colombia. Our
      surveys also uncovered 11 new ant records for the Colombian inter-Andean region
      and 2 new records for the country of Colombia: Mycocepurus curvispinosus (Mackay)
      and Rhopalothrix isthmica (Weber). The highest species richness was found in
      forest-covered sites, and richness and diversity was lower in the disturbed
      landscapes surrounding the forest patches. Species composition varied
      significantly between all habitat types, but was most similar between forest
      types suggesting that a loss of structural complexity has the greatest effect on
      ant communities. Across our study sites, ten species showed the greatest response
      to habitat type and could qualify as indicator taxa for this region. We conclude
      by discussing the value of conserving even small forests in this landscape due to
      their ability to retain high diversity of ants.

PMID- 29190002
TI  - Dentoalveolar Abscesses Not Associated with Caries or Trauma: A Diagnostic
      Hallmark of Hypophosphatemic Rickets Initially Misdiagnosed as Hypochondroplasia.
AB  - Hypophosphatemic rickets is a rare genetic disorder involving the regulation of
      fibroblast growth factor 23 (FGF23), a phosphaturic agent, clinically showing
      bowing of the legs, short stature and dentoalveolar abscesses. A 7-year-old boy,
      with previous hypochondroplasia diagnosis, was referred to our pediatric
      dentistry clinic presenting short stature, bone deformities and sinus tracts at
      deciduous teeth apex levels not related with trauma, restorations or dental
      caries. After deciduous teeth extraction, due to root resorption and mobility,
      light microscopy exhibited typical hypophosphatemic dentin, and micro-computed
      tomography revealed tubular clefts and porosities throughout the teeth.
      Laboratory tests confirmed the HR diagnosis, after which the treatment was
      initiated.

PMID- 29190003
TI  - p16 Immunohistochemistry in Oropharyngeal Squamous Cell Carcinoma Using the E6H4
      Antibody Clone: A Technical Method Study for Optimal Dilution.
AB  - Routine testing for p16 immunohistochemistry (with selective HPV-specific test
      use) has been recommended for clinical practice in oropharyngeal squamous cell
      carcinoma (OPSCC). Data suggests that the E6H4 clone performs best for this
      purpose, yet no studies have evaluated the optimal antibody concentration for
      OPSCC testing. We evaluated three concentrations (undiluted, 1:5, and 1:10) of
      the primary antibody solution for E6H4 using tissue microarrays from a cohort of
      199 OPSCC patients with a > 70% staining cutoff for positivity. Concordance was
      evaluated using percent agreement and Cohen's kappa. The concentrations were
      evaluated for sensitivity and specificity using high risk HPV RNA in situ
      hybridization (RNA-ISH) and also correlated with Kaplan-Meier overall survival
      analysis. Inter-rater agreement was very high between p16 results at each
      concentration and also with RNA in situ hybridization (p < 0.0001 for all).
      Agreement between p16 undiluted and 1:5 dilution (agreement 98.2%; Kappa 0.943; p
      < 0.0001) was very high and between p16 undiluted and 1:10 dilution (agreement
      79.2%; Kappa 0.512; p < 0.0001) much lower. Intensity of the staining did
      decrease with the 1:5 and 1:10 dilutions compared to undiluted, but not in a
      manner that obviously would change test interpretation or performance. Results
      suggest that the E6H4 antibody performs well at dilutions of up to 1:5 fold with
      a minor decrease in staining intensity, minimum loss of sensitivity, and no loss
      of specificity in OPSCC patients. This could result in reagent and cost savings.

PMID- 29190004
TI  - Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1
      randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early
      breast cancer.
AB  - PURPOSE: Although adjuvant polychemotherapy improves outcomes for early breast
      cancer, the significant variability in terms of pharmacokinetics results in
      differences in efficacy and both short and long-term toxicities. Retrospective
      studies support the use of dose tailoring according to the hematologic nadirs.
      METHODS: The SBG 2004-1 trial was a randomized feasibility phase II study which
      assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by
      docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC
      regimen (group C). Women aged 18-65 years, ECOG PS 0-1 with at least one positive
      axillary lymph node were randomized 1:1:1. The primary endpoint of the study was
      the safety and feasibility of the treatment. Toxicity was graded according to CTC
      AE version 3.0. The design and short-term toxicity have been previously
      published. Here, we report safety and efficacy data after 10 years of follow-up.
      RESULTS: A total of 124 patients were included in the study. After a median
      follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and
      63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C,
      respectively. There were no cases of clinically diagnosed cardiotoxicity or
      hematologic malignancies. No patient was lost to follow-up. CONCLUSIONS: In this
      randomized phase II trial, tailored dose adjuvant chemotherapy was feasible,
      without an increased risk for long-term adverse events after a median follow-up
      of 10 years.

PMID- 29190005
TI  - Associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality
      among Hispanic and non-Hispanic white women diagnosed with breast cancer: the
      Breast Cancer Health Disparities Study.
AB  - PURPOSE: ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is
      involved in the differentiation and protection of normal hematopoietic stem cells
      and functions in alcohol sensitivity and dependence. We evaluated the
      associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality
      among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the
      Breast Cancer Health Disparities Study. METHODS: Nine SNPs in ALDH1A1 were
      evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC.
      Adjusted Cox proportional hazard regression models were used to estimate hazard
      ratios (HRs) and 95% confidence intervals (CIs). Models were stratified by Native
      American (NA) ancestry and alcohol consumption. RESULTS: A total of 443 deaths
      occurred over a median follow-up time of 11 years. After adjusting all results
      for multiple comparisons, rs7027604 was significantly associated with all-cause
      mortality (HRAA = 1.40; 95% CI 1.13-1.73, P adj = 0.018). The rs1424482 CC
      genotype (HRCC = 1.69; 95% CI 1.20-2.37, P adj = 0.027) and the rs7027604 AA
      genotype (HRAA = 1.65; 95% CI 1.21-2.26, P adj = 0.018) were positively
      associated with non-BC mortality. Among long-term light drinkers, rs1888202 was
      associated with decreased all-cause mortality (HRCG/GG = 0.36; 95% CI 0.20-0.64),
      while associations were not significant among non-drinkers or moderate/heavy
      drinkers (P interation = 0.218). The increased risk of all-cause mortality
      associated with rs63319 was limited to women with low NA ancestry (HRAA = 1.53;
      95% CI 1.19-1.97). CONCLUSIONS: Multiple SNPs in ALDH1A1 were associated with
      increased risk of mortality after BC. Future BC studies examining the
      relationship between ALDH1A1 and mortality should consider the modifying effects
      of alcohol consumption and NA ancestry.

PMID- 29190007
TI  - Body Satisfaction During Pregnancy: The Role of Health-Related Habit Strength.
AB  - Objectives Body satisfaction during pregnancy is an important determinant of
      maternal and fetal health outcomes. It is therefore critical to investigate
      factors related to changes in body satisfaction and to elucidate how body
      satisfaction changes over time in pregnant women. The purpose of this study was
      to examine the relation between two novel factors (i.e., healthy eating habit
      strength and physical activity habit strength) and body satisfaction during
      pregnancy. Methods Participants (n = 67 pregnant North American women) completed
      online questionnaires at the beginning of their second trimester (Time 1) and at
      the end of pregnancy. Maternal characteristics, relationship satisfaction, self
      esteem, and psychological distress were assessed at Time 1 and habit strength,
      body satisfaction, and weight were assessed at both time points. Results Strength
      of healthy eating and physical activity habits remained stable over time and body
      satisfaction decreased over time. Healthy eating habit strength at Time 1
      predicted increases in body satisfaction from the second trimester to the end of
      pregnancy, even when controlling for gestational weight gain. Conclusions This
      study suggests that health-related habit strength in women of reproductive age
      may offer protection against low levels of body satisfaction during pregnancy.

PMID- 29190006
TI  - Trends in progression-free survival (PFS) and time to progression (TTP) over time
      within first-line aromatase inhibitors trials in hormone receptor-positive
      advanced breast cancer.
AB  - BACKGROUND: Over the last 20 years, aromatase inhibitors (AI) have been tested in
      clinical trials as first-line therapy for hormone receptor-positive (HR-positive)
      advanced breast cancer (ABC), firstly as experimental arms, when they proved to
      be effective, and recently as control arms. This analysis aims to evaluate trends
      in progression-free survival (PFS) and time to progression (TTP) over time.
      PATIENTS AND METHODS: A literature review was conducted using the MEDLINE
      database to identify randomized controlled phase II or III trials which reported
      PFS or TTP of at least one arm using first-line AI HR-positive ABC patients. A
      linear correlation was used to access the association between the year of the
      first patient enrolled and the observed PFS/TTP. RESULTS: The search retrieved 19
      trials, accounting for 4552 postmenopausal patients divided into 21 separate AI
      treatment arms. The PFS/TTP increased from 6 to 9 months in the earlier trials to
      13-16 months in the current era, representing an absolute gain of approximately 7
      months, without the addition of any other drug. Our analysis showed a positive
      correlation between the year of the first patient enrolled in these trials and
      median PFS/TTP reported (R 2 = 0.34; p < 0.01). No correlation was found between
      the year of the first patient included in these trials and other potential
      prognostic factors such as visceral metastasis at baseline (R 2 = 0.26; p = 0.20)
      or exposure to adjuvant therapy (R 2 = 0.05; p = 0.18). CONCLUSION: Patients
      treated with first-line AIs in the more recently conducted trials have longer
      PFS/TTP when compared to their counterparts treated with the same drugs in older
      studies. These findings have important implications for the estimation of sample
      size and follow-up periods for the planning of future trials as well as in the
      translation of the results into clinical practice decisions.

PMID- 29190008
TI  - The Development of the Healthy Pregnancy Stress Scale, and Validation in a Sample
      of Low-Income African American Women.
AB  - Objectives The association of stress with pregnancy health is well-known.
      However, few studies take a mixed methods approach to understand the stressors
      contributing to a woman's pregnancy-related stress. Among African American women,
      exposure to stressors during pregnancy likely contributes to disparities in
      pregnancy health outcomes. This work aimed to understand the types and magnitude
      of stressors African American women are exposed to during pregnancy. Methods
      Using a mixed methods research design, we developed and administered the Healthy
      Pregnancy Stress Scale to measure stressors within the stress environment of
      African American women living in poverty. Results Exploratory factor analysis
      with one random split-half sample (N = 85) identified a two-factor model. Factor
      1, defined as general pregnancy stressors, had significant loadings for ten items
      that ranged in magnitude from 0.319 to 0.724. Factor 2, defined as relationship
      strain, had significant loadings for three items ranging in magnitude from 0.613
      to 0.856. Confirmatory factor analysis in the second random split-half sample (N
      = 88) showed a strong fit for the two factor model with factor loadings similar
      in magnitude. Standard fit statistics and those that adjust for item non
      normality suggested an adequate fit to the data (RMSEA = 0.057, CFI = 0.947, TLI
      = 0.932; Satorra-Bentler RMSEA = 0.037, CFI = 0.972, TLI = 0.965). Conclusions
      for Practice Our measurement tool may provide a way to determine differences in
      pregnancy stress experiences across diverse populations of women. Future research
      should include a test for construct validity by correlating the scale with other
      measures that should have a specific directional relationship in diverse
      populations.

PMID- 29190009
TI  - Introduction to the Special Issue on Healthy Start.

PMID- 29190011
TI  - Relevance of genetic relationship in GWAS and genomic prediction.
AB  - The objective of this study was to analyze the relevance of relationship
      information on the identification of low heritability quantitative trait loci
      (QTLs) from a genome-wide association study (GWAS) and on the genomic prediction
      of complex traits in human, animal and cross-pollinating populations. The
      simulation-based data sets included 50 samples of 1000 individuals of seven
      populations derived from a common population with linkage disequilibrium. The
      populations had non-inbred and inbred progeny structure (50 to 200) with varying
      number of members (5 to 20). The individuals were genotyped for 10,000 single
      nucleotide polymorphisms (SNPs) and phenotyped for a quantitative trait
      controlled by 10 QTLs and 90 minor genes showing dominance. The SNP density was
      0.1 cM and the narrow sense heritability was 25%. The QTL heritabilities ranged
      from 1.1 to 2.9%. We applied mixed model approaches for both GWAS and genomic
      prediction using pedigree-based and genomic relationship matrices. For GWAS, the
      observed false discovery rate was kept below the significance level of 5%, the
      power of detection for the low heritability QTLs ranged from 14 to 50%, and the
      average bias between significant SNPs and a QTL ranged from less than 0.01 to
      0.23 cM. The QTL detection power was consistently higher using genomic
      relationship matrix. Regardless of population and training set size, genomic
      prediction provided higher prediction accuracy of complex trait when compared to
      pedigree-based prediction. The accuracy of genomic prediction when there is
      relatedness between individuals in the training set and the reference population
      is much higher than the value for unrelated individuals.

PMID- 29190012
TI  - The Role of Glycemic Control and Variability in Diabetic Retinopathy.
AB  - Diabetic retinopathy (DR) is a common microvascular complication of diabetes
      mellitus (DM) and is considered the leading cause of visual impairment in working
      aged adults worldwide. The duration of DM and hyperglycemia have been associated
      with DR, although the exact role in the pathogenesis of DR and diabetic macular
      edema remains controversial. As a result, a reasonable question arising is
      whether control of blood glucose levels may alter the course of DR. Studies have
      shown that glycemic control remains an important factor for the presence and
      progression of DR. HbA1c seems to be an indicator which cannot demonstrate
      exactly the degree of glycemic control, while sudden variations of blood glucose
      may play an important role in DR; therefore, glycemic variability may be useful
      to predict DM complications, such as DR.

PMID- 29190010
TI  - Are mechanically sensitive regulators involved in the function and
      (patho)physiology of cerebral palsy-related contractures?
AB  - Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical
      impacts and to translate these into biochemical signals making the tissue adapt.
      Among its mechanosensitive nature, skeletal muscle tissue is the largest
      metabolic organ of the human body. Disturbances in skeletal muscle mechanosensing
      and metabolism cause and contribute to many diseases, i.e. muscular
      dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type
      2. A less commonly focused muscle-related disorder is clinically known as muscle
      contractures that derive from cerebral palsy (CP) conditions in young and adults.
      Muscle contractures are characterized by gradually increasing passive muscle
      stiffness resulting in complete fixation of joints. Different mechanisms have
      been identified in CP-related contractures, i.e. altered calcium handling,
      altered metabolism or altered titin regulation. The muscle-related extracellular
      matrix (ECM), specifically collagens, plays a role in CP-related contractures.
      Herein, we focus on mechanically sensitive complexes, known as costameres
      (Cstms), and discuss their potential role in CP-related contractures. We extend
      our discussion to the ECM due to the limited knowledge of its role in CP-related
      contractures. The aims of this review are (1) to summarize CP-related contracture
      mechanisms, (2) to raise novel hypotheses on the genesis of contractures with a
      focus on Cstms, and (3) to stimulate novel approaches to study CP-related
      contractures.

PMID- 29190013
TI  - Use of Animal Models and Techniques in Glaucoma Research: Introduction.
AB  - This chapter provides an overview over the use of animal models in glaucoma
      research from a historical perspective. Strengths and limitations of various
      models are considered, and the challenges of translating results in animal
      experiments to successful clinical trials in humans are discussed.

PMID- 29190014
TI  - Hypertonic Saline Injection Model of Experimental Glaucoma in Rats.
AB  - A reliable method of creating chronic elevation of intraocular pressure (IOP) in
      rodents is an important tool in reproducing and studying the mechanisms of optic
      nerve injury that occur in glaucoma. In addition, such a model could provide a
      valuable method for testing potential neuroprotective treatments. This paper
      outlines the basic methods for producing obstruction of aqueous humor outflow and
      IOP elevation by injecting hypertonic saline (a sclerosant) into the aqueous
      outflow pathway. This is one of several rodent glaucoma models in use today. In
      this method, a plastic ring is placed around the equator of the eye to restrict
      injected saline to the limbus. By inserting a small glass microneedle in an
      aqueous outflow vein in the episclera and injecting hypertonic saline toward the
      limbus, the saline is forced into Schlemm's canal and across the trabecular
      meshwork. The resultant inflammation and scarring of the anterior chamber angle
      occurs gradually, resulting in a rise in IOP after approximately 1 week. This
      article will describe the equipment necessary for producing this model and the
      steps of the technique itself.

PMID- 29190015
TI  - The Microbead Occlusion Model of Ocular Hypertension in Mice.
AB  - Glaucoma is a common optic neuropathy that leads to vision loss through the
      degeneration of retinal ganglion cells (RGCs) and their axons. RGC degeneration
      in glaucoma is associated with sensitivity to intraocular pressure (IOP) and
      elevated IOP (also known as ocular hypertension) is the primary modifiable risk
      factor. Ocular hypertension is the primary characteristic of rodent models for
      glaucoma research. Intracameral injection of microbeads has evolved as a
      preferred method of IOP elevation in rodents, particularly in mice. Here, we
      outline the protocol and method for the Microbead Occlusion Model in mice. We
      highlight the importance of anesthesia choice and the utilization of glass
      micropipettes in combination with a micromanipulator and microsyringe pump for
      the successful execution of the model.

PMID- 29190016
TI  - Ocular Hypertension/Glaucoma in Minipigs: Episcleral Veins Cauterization and
      Microbead Occlusion Methods.
AB  - Two methods to induce elevation of the intraocular pressure (experimental
      glaucoma) are described in the present chapter. The first method is based on
      increasing the post-trabecular resistance to aqueous outflow by cauterizing the
      episcleral veins (EVC). This method allows the observation of ultrastructural
      changes in the trabecular meshwork (TM) without interfering with any structure
      within the eye such as TM, ciliary body, and/or the Retina. The second method is
      the multiple injection of microbeads into the anterior chamber, as a pre and
      intra-trabecular method that induce secondary effects on the TM cells. Both
      methods lead to an increase in IOP.

PMID- 29190017
TI  - Noninvasive Intraocular Pressure Measurement in Animals Models of Glaucoma.
AB  - Intraocular pressure (IOP) elevation is a critical risk factor for development
      and progression of glaucoma. As such, measuring IOP in animal models of the
      disease is important for any research work trying to understand the
      pathophysiologic mechanisms of glaucoma. Noninvasive IOP measurement in animals
      uses methods that have been adapted from use on humans. Calibration of the
      instruments used for the specific animal and even strain used is critically
      important for allowing meaningful comparisons of results. We describe below the
      methods used for noninvasive IOP measurement in animals that are relevant to
      glaucoma research.

PMID- 29190018
TI  - High-Throughput Binocular Pattern Electroretinograms in the Mouse.
AB  - We describe a new method for obtaining user-friendly, robust pattern
      electroretinograms (PERG) simultaneously from each eye using asynchronous
      binocular stimulation and one-channel acquisition of signals recorded from a
      subcutaneous needle in the snout.

PMID- 29190019
TI  - Visual Evoked Potentials in Glaucoma and Alzheimer's Disease.
AB  - Visual responses to gratings alternating in contrast have been studied in humans
      and several mammalian species. Previous evidence from human patients and animal
      models of neurodegeneration has highlighted the importance to record
      simultaneously the pattern electroretinogram (P-ERG) and visual evoked cortical
      potentials (VEPs) to investigate retinal and post-retinal sites of
      neurodegeneration.In view of the increasing importance of research on
      experimental models of neurodegenerative diseases, we present here the parametric
      properties of visual evoked responses in animal models of glaucoma and
      Alzheimer's disease. Glaucoma and Alzheimer's disease (AD) are two distinct
      multifactorial neurodegenerative and progressive diseases, primarily affecting
      the elderly.

PMID- 29190020
TI  - Investigation of the Functional Retinal Output Using Microelectrode Arrays.
AB  - Microelectrode array (MEA) recordings of the ex vivo flat-mounted retina enable
      the functional analysis of the retinal output. The electrical activity of a large
      portion of retinal ganglion cells (RGCs) is recorded simultaneously in response
      to various light stimuli. Analysis of the recorded time series of action
      potentials reveals physiological parameters such as firing rate, time latency,
      receptive field size, axonal conduction velocity. These parameters change during
      retinal diseases.

PMID- 29190021
TI  - Quantitative Proteomic Analysis of Human Aqueous Humor Using iTRAQ 4plex
      Labeling.
AB  - iTRAQ 4plex method enables multiplexing of up to four samples for simultaneous
      quantitation to improve sensitivity and scope of proteomic analysis. Here, we
      describe iTRAQ 4plex labeling of human aqueous humor specimens followed by ultra
      high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and
      data analysis for peptide identification and quantitation using Proteome
      Discoverer software. The protocol can be applied for other animals as well;
      however, pooling of specimens may be required to obtain sufficient amount of
      protein for labeling.

PMID- 29190022
TI  - Shotgun Sphingolipid Analysis of Human Aqueous Humor.
AB  - This protocol provides a step-by-step guide to shotgun sphingolipid analysis of
      aqueous humor. We describe the Bligh and Dyer crude lipid extraction method and
      electrospray ionization tandem mass spectrometry (ESI-MS/MS) coupled with MZmine
      2.21 data processing for identification and ratiometric quantitation of
      sphingosine, sphingosine-1-phosphate, sphingomyelin, and ceramide.

PMID- 29190023
TI  - Assessment of Aqueous Humor Dynamics in the Rodent by Constant Flow Infusion.
AB  - Mice and rats are being increasingly used in glaucoma research and much useful
      data have been generated from them. One aspect of using these animals for this
      purpose involves assessment of aqueous humor dynamics. Several techniques have
      been described in the literature for the determination of one or more of these
      parameters in rodents, in both living animals and eyes perfused ex vivo. Here, we
      describe the practical details for a technique for the determination of all
      principal parameters of aqueous humor dynamics (intraocular pressure (IOP),
      aqueous humor formation rate (Fin), uveoscleral outflow rate (Fu), aqueous
      outflow facility (C), and episcleral venous pressure (Pe)) in the living rat and
      mouse eye, in a single experimental session.

PMID- 29190024
TI  - Methods for Analyzing Endoplasmic Reticulum Stress in the Trabecular Meshwork of
      Glaucoma Models.
AB  - The pathological mechanisms underlying increased outflow resistance at the
      trabecular meshwork (TM) that is responsible for elevating intraocular pressure
      (IOP) have not been fully delineated. Recent studies have shown that progressive
      accumulation of misfolded proteins and induction of endoplasmic reticulum (ER)
      stress is associated with the pathophysiology of glaucomatous TM damage and IOP
      elevation. We have shown that known causes of human glaucoma, including
      expression of mutant myocilin or dexamethasone treatment induce abnormal protein
      accumulation and ER stress in the TM in vitro and in vivo models. To cope up with
      abnormal protein accumulation, TM cells activate a cytoprotective pathway of
      unfolded protein response (UPR). However, chronic ER stress can lead to TM
      dysfunction and IOP elevation. Using cell culture, mouse models, and human
      postmortem tissues as well as genetic and pharmacological manipulations, we have
      analyzed ER stress and UPR mediators in the glaucomatous TM damage and IOP
      elevation. In this chapter, we have described a detailed protocol for the
      analysis of protein misfolding and ER stress in TM cells and tissues and its
      association with glaucomatous TM damage and IOP elevation.

PMID- 29190025
TI  - Quantification of Scleral Biomechanics and Collagen Fiber Alignment.
AB  - The stiffness of the sclera is important in several ocular disorders, and there
      is hence a need to quantify the biomechanical properties of this tissue. Here, we
      present two methods for measuring the stiffness of scleral ocular tissues: ocular
      compliance testing and digital image correlation strain mapping. In tandem with
      these approaches, we provide two methods to spatially quantify the anisotropic
      alignment of collagen fibers making up the sclera, using second harmonic
      generation microscopy and small-angle light scattering. Together, these
      approaches allow specimen-specific measurement of tissue stiffness and collagen
      alignment, which are key factors in determining how the eye responds to
      mechanical loads.

PMID- 29190026
TI  - Biolistic Labeling of Retinal Ganglion Cells.
AB  - Labeling of cellular structures is of fundamental importance in the investigation
      of diseases of the central nervous system. Biolistic labeling of retinal ganglion
      cells (RGCs) allows visualization of dendritic and synaptic structures of RGCs in
      retinal explants from animal models of experimental glaucoma. This technique
      sparsely labels RGCs, and, due to the stochastic nature of the particle delivery,
      all RGC types can be potentially observed in the labeled tissue. Quantification
      of dendritic and synaptic properties permits examination of the specific
      alterations to RGC morphology at different stages of degeneration, such as
      dendritic shrinkage and excitatory synapse loss.

PMID- 29190027
TI  - Anterograde Tract Tracing for Assaying Axonopathy and Transport Deficits in
      Glaucoma.
AB  - Whether to stage degeneration or investigate early pathology in glaucoma,
      examination of axonal structure and function is essential. There are a wide
      variety of methods available to investigators using animal models of glaucoma,
      with varying utilities depending on the questions asked. Here, we describe the
      use of anterograde neuronal tract tracing using cholera toxin B (CTB) for the
      determination of axon transport integrity of the retinofugal projection. This
      method reveals the structure of the retinal axons as well as the functional
      integrity of anterograde transport systems.

PMID- 29190028
TI  - In Vitro and In Vivo Methods for Studying Retinal Ganglion Cell Survival and
      Optic Nerve Regeneration.
AB  - Glaucoma is marked by a progressive degeneration of the optic nerve and delayed
      loss of retinal ganglion cells (RGCs), the projection neurons of the eye. Because
      RGCs are not replaced and because surviving RGCs cannot regenerate their axons,
      the visual loss in glaucoma is largely irreversible. Here, we describe methods to
      evaluate treatments that may be beneficial for treating glaucoma using in vitro
      cell culture models (immunopanning to isolate neonatal RGCs, dissociated mature
      retinal neurons, retinal explants) and in vivo models that test potential
      treatments or investigate underlying molecular mechanisms in an intact system.
      Potentially, use of these models can help investigators continue to improve
      treatments to preserve RGCs and restore visual function in patients with
      glaucoma.

PMID- 29190029
TI  - 3D Histomorphometric Reconstruction and Quantification of the Optic Nerve Head
      Connective Tissues.
AB  - Accurately characterizing the 3D geometry of the optic nerve head neural and
      connective tissues has been the goal of a large and important body of scientific
      work. In the present report, we summarize our methods for the high-resolution,
      digital, 3D histomorphometric reconstruction of the optic nerve head tissues,
      including their visualization, parameterization, and quantification. In addition,
      we present our methods for between-eye comparisons of this anatomy, and their use
      to determine animal-specific and experiment-wide experimental glaucoma versus
      Control eye differences in the unilateral, monkey experimental glaucoma model.
      Finally, we demonstrate its application to finite element modeling, 3D optic
      nerve head reconstruction of other species, and 3D optic nerve head
      reconstructions using other imaging modalities.

PMID- 29190030
TI  - Visualizing Astrocytes of the Optic Nerve.
AB  - Astrocytes make up approximately 30% of all the cells in the mammalian central
      nervous system. They are not passive, as once thought, but are integral to brain
      physiology and perform many functions that are important for normal neuronal
      development and metabolism, synapse formation, synaptic transmission, and in
      repair following injury/disease. Astrocytes also communicate with neurons, blood
      vessels, and other types of glial cells. Astrocytes within the optic nerve head
      region play a key role in glaucomatous axon degeneration. In this chapter, we
      describe ways in which astrocytes of the optic nerve head can be visualized,
      beginning with basic immunohistochemical staining methods, to single-cell dye
      injections and then to transgenic animals. We will also discuss the pros and cons
      of each method. Many of the methods were initially developed to visualize brain
      astrocytes; in some cases, the method has translated well to astrocytes of the
      optic nerve, and in others, it remains unclear.

PMID- 29190031
TI  - Investigation of MicroRNA Expression in Experimental Glaucoma.
AB  - MicroRNAs are small, endogenous noncoding RNAs that modulate post-transcriptional
      gene expression. Recent evidence suggests that they may have a potential role in
      the regulation of the complex biological responses that develop in response to
      elevated intraocular pressure. However, contemporary microRNA assay techniques
      (e.g., microarrays and next-generation sequencing) typically require large
      amounts of RNA template that are often times difficult to obtain from
      glaucomatous tissue. We describe in detail an experimental protocol utilizing
      targeted pre-amplification and low-density polymerase chain reaction arrays to
      circumvent this hurdle. This approach optimizes the simultaneous high-throughput
      screening of small tissue samples, such as the rodent optic nerve head, for up to
      754 microRNA probes while also providing an opportunity for subsequent
      confirmatory reactions of technical or biological replicates.

PMID- 29190032
TI  - Utilizing RNA-Seq to Identify Differentially Expressed Genes in Glaucoma Model
      Tissues, Such as the Rodent Optic Nerve Head.
AB  - Understanding the cellular pathways activated by elevated intraocular pressure
      (IOP) is crucial for the development of more effective glaucoma treatments.
      Microarray studies have previously been used to identify several key gene
      expression changes in early and extensively injured ONH, as well as in the
      retina. Limitations of microarrays include that they can only be used to detect
      transcripts that correspond to existing genomic sequencing information and their
      narrower dynamic range. However, RNA sequencing (RNA-seq) is a powerful tool for
      investigating known transcripts, as well as for exploring new ones (including
      noncoding RNAs and small RNAs), is more quantitative, and has the added benefit
      that the data can be re-analyzed as new sequencing information becomes available.
      Here, we describe an RNA-seq method specifically developed for identifying
      differentially expressed genes in optic nerve heads of eyes exposed to elevated
      intraocular pressure. The methods described here could also be applied to small
      tissue samples (less than 100 ng in total RNA yield) from retina, optic nerve, or
      other regions of the central nervous system.

PMID- 29190033
TI  - Single-Cell Dissociation and Characterization in the Murine Retina and Optic
      Nerve.
AB  - Recent technological advances have extended the range of analytic tools to very
      small samples. It is now possible to assay the transcriptome, and in some cases
      even the proteome, of single cells reliably. This allows addressing novel
      questions, such as the genotype/phenotype relationships of single neurons,
      heterogeneity within individual cells of the same type, or the basis of
      differential vulnerability to injury. An important prerequisite for these kinds
      of studies is the ability to isolate well-defined individual cells without
      contamination by adjacent tissue. In the retina and optic nerve, cells of
      different types and functions are closely intermingled, limiting the use of
      standard methods such as laser capture microdissection. Here, we describe a
      simple method to isolate morphologically intact cells from the retina and the
      optic nerve and discuss considerations in recognizing and isolating different
      cell types after dissociation.

PMID- 29190035
TI  - Impact assessment of projected climate change on diffuse phosphorous loss in
      Xin'anjiang catchment, China.
AB  - Diffuse nutrient loss is a serious threat to water security and has severely
      deteriorated water quality throughout the world. Xin'anjiang catchment, as a main
      drinking water source for Hangzhou City, has been a national concern for water
      environment protection with payment for watershed services construction.
      Detection of diffuse phosphorous (DP) pollution dynamics under climate change is
      significant for sustainable water quality management. In this study, the impact
      of projected climate change on DP load was analyzed using SWAT to simulate the
      future changes of diffuse components (carriers: water discharge and sediment;
      nutrient: DP) at both station and sub-catchment scales under three climate change
      scenarios (RCP2.6, RCP4.5, and RCP8.5). Results showed that wetting and warming
      years were expected with increasing tendencies of both precipitation and
      temperature in the two future periods (2020s: 2021~2030, 2030s: 2031~2040) except
      in the 2020s in the RCP2.6 scenario, and the annual average increasing ratios of
      precipitation and temperature reached - 1.79~3.79% and 0.48~1.27  degrees C,
      respectively, comparing with those in the baseline (2000s: 2001~2010). Climate
      change evidently altered annual and monthly average water discharge and sediment
      load, while it has a remarkable impact on the timing and monthly value of DP load
      at station scale. DP load tended to increase in the non-flood season at Yuliang
      due to strengthened nutrient flushing from rice land into rivers with increasing
      precipitation and enhanced phosphorous cycle in soil layers with increasing
      temperature, while it tended to decrease in the flood season at Yuliang and in
      most months at Tunxi due to restricted phosphorous reaction with reduced
      dissolved oxygen content and enhanced dilution effect. Spatial variability
      existed in the changes of sediment load and DP load at sub-catchment scale due to
      climate change. DP load tended to decrease in most sub-catchments and was the
      most remarkable in the RCP8.5 scenario (2020s, - 9.00~2.63%; 2030s, -
      11.16~7.89%), followed by RCP2.6 (2020s, - 10.00~2.90%; 2030s, - 9.00~6.63%) and
      RCP4.5 (2020s, - 6.81~5.49%, 2030s, - 10.00~9.09%) scenarios. Decreasing of DP
      load mainly aggregated in the western and eastern mountainous regions, while it
      tended to increase in the northern and middle regions. This study was expected to
      provide insights into diffuse nutrient loss control and management in Xin'anjiang
      catchment, and scientific references for the implementation of water
      environmental protection in China.

PMID- 29190036
TI  - Devices for preventing percutaneous exposure injuries caused by needles in
      healthcare personnel.
AB  - BACKGROUND: Percutaneous exposure injuries from devices used for blood collection
      or for injections expose healthcare workers to the risk of blood borne infections
      such as hepatitis B and C, and human immunodeficiency virus (HIV). Safety
      features such as shields or retractable needles can possibly contribute to the
      prevention of these injuries and it is important to evaluate their effectiveness.
      OBJECTIVES: To determine the benefits and harms of safety medical devices aiming
      to prevent percutaneous exposure injuries caused by needles in healthcare
      personnel versus no intervention or alternative interventions. SEARCH METHODS: We
      searched CENTRAL, MEDLINE, EMBASE, NHSEED, Science Citation Index Expanded,
      CINAHL, Nioshtic, CISdoc and PsycINFO (until 11 November 2016). SELECTION
      CRITERIA: We included randomised controlled trials (RCT), controlled before and
      after studies (CBA) and interrupted time-series (ITS) designs of the effect of
      safety engineered medical devices on percutaneous exposure injuries in healthcare
      staff. DATA COLLECTION AND ANALYSIS: Two of the authors independently assessed
      study eligibility and risk of bias and extracted data. We synthesized study
      results with a fixed-effect or random-effects model meta-analysis where
      appropriate. MAIN RESULTS: We included six RCTs with 1838 participants, two
      cluster-RCTs with 795 participants and 73,454 patient days, five CBAs with
      approximately 22,000 participants and eleven ITS with an average of 13.8 data
      points. These studies evaluated safe modifications of blood collection systems,
      intravenous (IV) systems, injection systems, multiple devices, sharps containers
      and legislation on the implementation of safe devices. We estimated the
      needlestick injury (NSI) rate in the control groups to be about one to five NSIs
      per 1000 person-years. There were only two studies from low- or middle-income
      countries. The risk of bias was high in 20 of 24 studies. Safe blood collection
      systems:We found one RCT that found a safety engineered blood gas syringe having
      no considerable effect on NSIs (Relative Risk (RR) 0.2, 95% Confidence Interval
      (95% CI) 0.01 to 4.14, 550 patients, very low quality evidence). In one ITS
      study, safe blood collection systems decreased NSIs immediately after the
      introduction (effect size (ES) -6.9, 95% CI -9.5 to -4.2) but there was no
      further decrease over time (ES -1.2, 95% CI -2.5 to 0.1, very low quality
      evidence). Another ITS study evaluated an outdated recapping shield, which we did
      not consider further. Safe Intravenous systemsThere was very low quality evidence
      in two ITS studies that NSIs were reduced with the introduction of safe IV
      devices, whereas one RCT and one CBA study provided very low quality evidence of
      no effect. However, there was moderate quality evidence produced by four other
      RCT studies that these devices increased the number of blood splashes when the
      safety system had to be engaged actively (relative risk (RR) 1.6, 95% CI 1.08 to
      2.36). In contrast there was low quality evidence produced by two RCTs of passive
      systems that showed no effect on blood splashes. Yet another RCT produced low
      quality evidence that a different safe active IV system also decreased the
      incidence of blood leakages. Safe injection devicesThere was very low quality
      evidence provided by one RCT and one CBA study showing that introduction of safe
      injection devices did not considerably change the NSI rate. One ITS study
      produced low quality evidence showing that the introduction of safe passive
      injection systems had no effect on NSI rate when compared to safe active
      injection systems. Multiple safe devicesThere was very low quality evidence from
      one CBA study and two ITS studies. According to the CBA study, the introduction
      of multiple safe devices resulted in a decrease in NSI,whereas the two ITS
      studies found no change. Safety containersOne CBA study produced very low quality
      evidence showing that the introduction of safety containers decreased NSI.
      However, two ITS studies evaluating the same intervention found inconsistent
      results. LegislationThere was low to moderate quality evidence in two ITS studies
      that introduction of legislation on the use of safety-engineered devices reduced
      the rate of NSIs among healthcare workers. There was also low quality evidence
      which showed a decrease in the trend over time for NSI rates.Twenty out of 24
      studies had a high risk of bias and the lack of evidence of a beneficial effect
      could be due to both confounding and bias. This does not mean that these devices
      are not effective. AUTHORS' CONCLUSIONS: For safe blood collection systems, we
      found very low quality evidence of inconsistent effects on NSIs. For safe passive
      intravenous systems, we found very low quality evidence of a decrease in NSI and
      a reduction in the incidence of blood leakage events but moderate quality
      evidence that active systems may increase exposure to blood. For safe injection
      needles, the introduction of multiple safety devices or the introduction of
      sharps containers the evidence was inconsistent or there was no clear evidence of
      a benefit. There was low to moderate quality evidence that introduction of
      legislation probably reduces NSI rates.More high-quality cluster-randomised
      controlled studies that include cost-effectiveness measures are needed,
      especially in countries where both NSIs and blood-borne infections are highly
      prevalent.

PMID- 29190037
TI  - Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal
      infectious morbidity.
AB  - BACKGROUND: Infectious morbidities contribute to considerable maternal and
      perinatal morbidity and mortality, including women at no apparent increased risk
      of infection. To reduce the incidence of infections, antibiotics are often
      administered to women after uncomplicated childbirth, particularly in settings
      where women are at higher risk of puerperal infectious morbidities. OBJECTIVES:
      To assess whether routine administration of prophylactic antibiotics to women
      after normal (uncomplicated) vaginal birth, compared with placebo or no
      antibiotic prophylaxis, reduces postpartum maternal infectious morbidities and
      improves outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (31 August 2017), LILACS, ClinicalTrials.gov,
      the WHO International Clinical Trials Registry Platform (ICTRP) (22 August 2017)
      and reference lists of retrieved studies. SELECTION CRITERIA: We planned to
      include randomised or quasi-randomised trials evaluating the use of prophylactic
      antibiotics versus placebo or no antibiotic prophylaxis. Trials using a cluster
      randomised design would have been eligible for inclusion, but we found none.In
      future updates of this review, we will include studies published in abstract form
      only, provided sufficient information is available to assess risks of bias. We
      will consider excluded abstracts for inclusion once the full publication is
      available, or the authors provide more information.Trials using a cross-over
      design are not eligible for inclusion in this review. DATA COLLECTION AND
      ANALYSIS: Two review authors conducted independent assessment of trials for
      inclusion and risks of bias. They independently extracted data and checked them
      for accuracy, resolving differences in assessments by discussion. They evaluated
      methodological quality using standard Cochrane criteria and the GRADE approach.We
      present the summaries as risk ratios (RRs) and mean difference (MDs) using fixed-
      or random-effect models. For one primary outcome we found considerable
      heterogeneity and interaction. We explored further using subgroup analysis to
      investigate the effects of the randomisation unit. All review authors discussed
      and interpreted the results. MAIN RESULTS: One randomised controlled trial (RCT)
      and two quasi-RCTs contributed data on 1779 women who had uncomplicated vaginal
      births, comparing different antibiotic regimens with placebo or no treatment. The
      included trials took place in the 1960s (one trial) and 1990s (two trials). The
      trials were conducted in France, the USA and Brazil. Antibiotics administered
      included: oral sulphamethoxypyridazine or chloramphenicol for three to five days,
      and intravenous amoxicillin and clavulanic acid in a single dose one hour after
      birth. We rated most of the domains for risk of bias as high risk, with the
      exception of reporting bias and other potential bias.The quality of evidence
      ranged from low to very low, based on the GRADE quality assessment, given very
      serious design limitations of the included studies, few events and wide
      confidence intervals (CIs) of effect estimates.We found a decrease in the risk of
      endometritis (RR 0.28, 95% CI 0.09 to 0.83, two trials, 1364 women,very low
      quality). However, one trial reported zero events for this outcome and we rate
      the evidence as very low quality. There was little or no difference between
      groups for the risk of urinary tract infection (RR 0.25, 95% CI 0.05 to 1.19, two
      trials, 1706 women,low quality), wound infection after episiotomy (reported as
      wound dehiscence in the included trials) (RR 0.78, 95% CI 0.31 to 1.96, two
      trials, 1364 women, very low quality) and length of maternal hospital stay in
      days (MD -0.15, 95% CI -0.31 to 0.01, one trial, 1291 women, very low quality).
      Cost of care in US dollar equivalent was 21/2 times higher in the control group
      compared to the group receiving antibiotics prophylaxis (USD 3600: USD 9000, one
      trial, 1291 women). There were few or no differences between treated and control
      groups for adverse effects of antibiotics (skin rash) reported in one woman in
      each of the two trials (RR 3.03, 95% CI 0.32 to 28.95, two trials, 1706 women,
      very low quality). The incidence of severe maternal infectious morbidity,
      antimicrobial resistance or women's satisfaction with care were not addressed by
      any of the included studies. AUTHORS' CONCLUSIONS: Routine administration of
      antibiotics may reduce the risk of endometritis after uncomplicated vaginal
      birth. The small number and nature of the trials limit the interpretation of the
      evidence for application in practice, particularly in settings where women may be
      at higher risk of developing endometritis. The use of antibiotics did not reduce
      the incidence of urinary tract infections, wound infection or the length of
      maternal hospital stay. Antibiotics are not a substitute for infection prevention
      and control measures around the time of childbirth and the postpartum period. The
      decision to routinely administer prophylactic antibiotics after normal vaginal
      births needs to be balanced by patient features, childbirth setting and provider
      experience, including considerations of the contribution of indiscriminate use of
      antibiotics to raising antimicrobial resistance. Well-designed and high-powered
      randomised controlled trials would help to evaluate the added value of routine
      antibiotic administration as a measure to prevent maternal infections after
      normal vaginal delivery.

PMID- 29190034
TI  - The role of alphaB-crystallin in skeletal and cardiac muscle tissues.
AB  - All organisms and cells respond to various stress conditions such as
      environmental, metabolic, or pathophysiological stress by generally upregulating,
      among others, the expression and/or activation of a group of proteins called heat
      shock proteins (HSPs). Among the HSPs, special attention has been devoted to the
      mutations affecting the function of the alphaB-crystallin (HSPB5), a small heat
      shock protein (sHsp) playing a critical role in the modulation of several
      cellular processes related to survival and stress recovery, such as protein
      degradation, cytoskeletal stabilization, and apoptosis. Because of the emerging
      role in general health and disease conditions, the main objective of this mini
      review is to provide a brief account on the role of HSPB5 in mammalian muscle
      physiopathology. Here, we report the current known state of the regulation and
      localization of HSPB5 in skeletal and cardiac tissue, making also a critical
      summary of all human HSPB5 mutations known to be strictly associated to specific
      skeletal and cardiac diseases, such as desmin-related myopathies (DRM), dilated
      (DCM) and restrictive (RCM) cardiomyopathy. Finally, pointing to putative
      strategies for HSPB5-based therapy to prevent or counteract these forms of human
      muscular disorders.

PMID- 29190038
TI  - Closure methods of the appendix stump for complications during laparoscopic
      appendectomy.
AB  - BACKGROUND: Laparoscopic appendectomy is amongst the most common general surgical
      procedures performed in the developed world. Arguably, the most critical part of
      this procedure is effective closure of the appendix stump to prevent catastrophic
      intra-abdominal complications from a faecal leak into the abdominal cavity. A
      variety of methods to close the appendix stump are used worldwide; these can be
      broadly divided into traditional ligatures (such as intracorporeal or
      extracorporeal ligatures or Roeder loops) and mechanical devices (such as
      stapling devices, clips, or electrothermal devices). However, the optimal method
      remains unclear. OBJECTIVES: To compare all surgical techniques now used for
      appendix stump closure during laparoscopic appendectomy. SEARCH METHODS: In June
      2017, we searched the Cochrane Central Register of Controlled Trials (CENTRAL;
      2017, Issue 6) in the Cochrane Library, MEDLINE Ovid (1946 to 14 June 2017),
      Embase Ovid (1974 to 14 June 2017), Science Citation Index - Expanded (14 June
      2017), China Biological Medicine Database (CBM), the World Health Organization
      International Trials Registry Platform search portal, ClinicalTrials.gov, Current
      Controlled Trials, the Chinese Clinical Trials Register, and the EU Clinical
      Trials Register (all in June 2017). We searched the reference lists of relevant
      publications as well as meeting abstracts and Conference Proceedings Citation
      Index to look for additional relevant clinical trials. SELECTION CRITERIA: We
      included all randomised controlled trials (RCTs) that compared mechanical
      appendix stump closure (stapler, clips, or electrothermal devices) versus
      ligation (Endoloop, Roeder loop, or intracorporeal knot techniques) for
      uncomplicated appendicitis. DATA COLLECTION AND ANALYSIS: Two review authors
      identified trials for inclusion, collected data, and assessed risk of bias
      independently. We performed the meta-analysis using Review Manager 5. We
      calculated the odds ratio (OR) for dichotomous outcomes and the mean difference
      (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS:
      We included eight randomised studies encompassing 850 participants. Five studies
      compared titanium clips versus ligature, two studies compared an endoscopic
      stapler device versus ligature, and one study compared an endoscopic stapler
      device, titanium clips, and ligature. In our analyses of primary outcomes, we
      found no differences in total complications (OR 0.97, 95% CI 0.27 to 3.50, 8
      RCTs, very low-quality evidence), intraoperative complications (OR 0.93, 95% CI
      0.34 to 2.55, 8 RCTs, very low-quality evidence), or postoperative complications
      (OR 0.80, 95% CI 0.21 to 3.13, 8 RCTs, very low-quality evidence) between
      ligature and all types of mechanical devices. However, our analyses of secondary
      outcomes revealed that use of mechanical devices saved approximately nine minutes
      of total operating time when compared with use of a ligature (mean difference
      (MD) -9.04 minutes, 95% CI -12.97 to -5.11 minutes, 8 RCTs, very low-quality
      evidence). However, this finding did not translate into a clinically or
      statistically significant reduction in inpatient hospital stay (MD 0.02 days, 95%
      CI -0.12 to 0.17 days, 8 RCTs, very low-quality evidence). Available information
      was insufficient for reliable comparison of total hospital costs and
      postoperative pain/quality of life between the two approaches. Overall, evidence
      across all analyses was of very low quality, with substantial potential for
      confounding factors. Given the limitations of all studies in terms of bias and
      the low quality of available evidence, a clear conclusion regarding superiority
      of any one particular type of mechanical device over another is not possible.
      AUTHORS' CONCLUSIONS: Evidence is insufficient at present to advocate omission of
      conventional ligature-based appendix stump closure in favour of any single type
      of mechanical device over another in uncomplicated appendicitis.

PMID- 29190039
TI  - Blood cell integrins and diseases.
AB  - Integrins are adhesion molecules on the surface of cells. In blood cells they are
      responsible for rapid changes during adhesion of the cell to the endothelium.
      Deficiency or defective function of integrins will result in severe illnesses.
      Surprisingly, certain variants of integrins are associated with an increased risk
      of developing SLE. In autoimmune diseases and as a result of organ
      transplantations integrins participate in reactions in which leukocytes attack
      the body's own tissues. This has resulted in the development of drugs in antibody
      form for inhibition of the action of integrins. These drugs may, however, exhibit
      severe adverse effects.

PMID- 29190040
TI  - Baroreflex activation therapy in the treatment of resistant hypertension.
AB  - Baroreceptors are sensory nerve endings in the carotid sinuses and the aortic
      arch. Notably, a dysfunction in the autonomic nervous system (sympathetic
      hyperactivity) has been shown to be part of the pathophysiology of chronic
      hypertension. Baroreflex activation therapy is an invasive treatment modality to
      decrease blood pressure by stimulating baroreceptors in the wall of the carotid
      sinus. Preliminary results of baroreflex activation therapy in resistant
      hypertension and systolic heart failure have been promising. If its effect can be
      proven in controlled studies, it may serve as an important new tool in the
      treatment of patients with resistant hypertension at a high risk of
      cardiovascular complications.

PMID- 29190041
TI  - Doppler imaging in inflammatory rheumatic diseases.
AB  - Doppler imaging has increased in rheumatology during this millennium. The method
      can detect slow blood flow in inflamed synovium and soft tissues. Doppler imaging
      is more sensitive than clinical examination in the detection of joint
      inflammation. Ultrasound imaging combined with Doppler imaging is regarded as
      reference method in the evaluation of enthesitis,. Doppler imaging is an
      excellent tool in the diagnostics and follow up in the treatment of the
      inflammatory rheumatic diseases because it does not use radiation, can be
      performed bedside and repeated often. The adjustment of ultrasound and Doppler
      signal is machine specific.

PMID- 29190042
TI  - Health effects of mindfulness - what should the doctor know?
AB  - There is solid evidence of the alleviation with mindfulness of chronic pain,
      symptoms of anxiety and depression and recurrent depression as well as
      enhancement of immunity. A dose-response relationship has been observed between
      the amount of practicing mindfulness and alleviation of stress and mood symptoms,
      and practicing is associated with structural and functional alterations in the
      brain. Mindfulness interventions are effective and suited for many kinds of human
      groups. Through increased ability to be present and increased compassion, the
      doctor's own mindfulness practicing may support the patient-doctor relationship

PMID- 29190043
TI  - Monitoring of blood glucose level in2016.
AB  - Self-care of insulin-tretated diabetes has in recent years become considerably
      more technical. Continuous glucose sensoring, measuring the glucose level of
      tissue fluid, has become an important tool for the management of glucose values
      in the everyday life of the diabetic patient. Detailed guidance to the use of the
      devices is essential in their utilization. The first glucose sensor requiring no
      calibration though the measurement of blood glucose level has also entered the
      market. Numerous smartphone applications for self-monitoring have emerged, and
      cloud services are being increasingly used for mediating data between the patient
      and the health facility. The Nightscout system makes remote monitoring of
      diabetic patients possible with a smart device.

PMID- 29190044
TI  - Liver abscess and sepsis caused by clostridium perfringens.
AB  - There is usually enough time for identifying the etiology of calculous
      cholestasis and cholangitis by imaging and laboratory investigations, provided
      that antimicrobial drug therapy is started immediately after collection of blood
      cultures and the patient's general condition is good. The situation changes, if
      the inflammation is caused by Clostridium perfringens, a rare causative agent of
      severe sepsis and massive intravascular hemolysis. Mortality from the resulting
      infection and sepsis is as high as over 70%. Quick recognition of the condition,
      initiation of antimicrobial drug therapy and drainage of a possible focus of
      infection may save the patient's life.

PMID- 29190045
TI  - Biomarkers of neutropenic sepsis.
AB  - Neutropenic sepsis is a common clinical problem in hematological patients
      receiving intensive chemotherapy. Complications will develop in a minority of
      these patients. Biomarkers can be used for the recognition of infection as well
      as to estimate its severity and risk of complications and also to assess
      treatment response. Experience gained from other patient groups or sepsis
      patients treated in intensive care units cannot be directly extrapolated to
      hematological patients. Numerous biomarkers of infections have been investigated
      in hematological patients, but no optimal marker has been found. C-reactive
      protein is still the most commonly used biomarker in hematological patients, but
      procalcitonin may be a real challenger, although more studies are still needed.

PMID- 29190046
TI  - Relapsing fever.
AB  - Relapsing fewer is an infection to be considered in the differential diagnosis of
      an immigrant's febrile illness. It is a severe, tick-borne or body louse-borne
      infection caused by the relapsing fever associated borrelia species. The body
      louse-borne infection is in particular encountered in the Horn of Africa region
      due to poor hygiene, and has during the past year been described in several
      European countries as imported by refugees coming from this region. Doctors
      should thus bear relapsing fever in mind as a differential diagnosis in a febrile
      refugee having recently arrived in Finland.

PMID- 29190047
TI  - Exosomes in cerebral diseases - novel form of intercellular communication.
AB  - Exosomes are vesicles bordered by a lipid membrane and containing various
      molecules. Virtually all cells in the body are able to secrete exosomes that can
      be carried long distances within the body and are capable of altering the
      function of the receiving cell by means of the contained molecules. The amount
      and composition of molecules contained in exosomes have been shown to differ in
      various diseases, whereby exosomes can be utilized in diagnostic purposes.
      Furthermore, it may be possible to use exosomes for the treatment of diseases,
      because they can carry therapeutic molecules in the body.

PMID- 29190048
TI  - Why is excessive sitting a health risk?
AB  - Increased epidemiological evidence over the past few years has shown excessive
      sitting to be a health risk even if recommendations for physical activity are
      fulfilled. Sitting is an independent health risk for two reasons: sitting and
      physical activity exhibit poor correlation, and an increase in physical activity
      does not contribute to all mechanisms underlying the health risks of sitting.
      During sitting, muscular passivity increases insulin resistance and influences
      the transport and oxidation of fatty acids in muscular tissue, and acute exercise
      is not sufficient to restore all changes. Accordingly, adequate everyday physical
      activity seems to be important for maintaining the signaling pathways affecting
      insulin sensitivity.

PMID- 29190049
TI  - Imaging of an acute stroke patient when planning therapy for arterial thrombosis.
AB  - Intra-arterial thrombectomy is a highly effective mode of treatment for properly
      selected patients with acute cerebral ischemia. Imaging studies are essential for
      making a decision on the treatment of acute cerebral infarction. In imaging, a
      combination of unenhanced CT scan of the head and CT angiography of the carotid
      and cerebral arteries during one imaging procedure is recommended for all
      patients coming into the hospital within the time window for thrombectomy, for
      patients with unclear time of onset of the symptoms and for whom cerebral
      hemorrhage is excluded as the cause in unenhanced CT scan. This may further be
      complemented with CT perfusion imaging. In certain acute situations magnetic
      resonance imaging is also useful.

PMID- 29190050
TI  - T cells and cancer - why do the killers become exhausted?
AB  - Nascent tumors are mostly eliminated by the immune system. During carcinogenesis
      mutated cells find a way to escape from the immune system's surveillance. As the
      tumor microenvironment evolves it becomes increasingly difficult for T cells to
      recognize and kill cancer cells. Recently, novel immunological targets have been
      recognized and potent immunomodulatory drugs discovered in clinical trials. This
      has resulted in the emergence of immunotherapy as a novel potent therapy for
      cancer in addition to chemotherapy, targeted therapy, operative therapy and
      radiotherapy.

PMID- 29190051
TI  - Headache as symptom of intracranial hemorrhage.
AB  - The most important signs of danger of a headache patient include exceptionally
      intense or acute headache, transient loss or progressive impairment of
      consciousness, and neurological deficit symptoms. These patients are referred to
      an urgent assessment by a physician. Computed tomography scanning of the head is
      carried out in the case of suspected hemorrhage of a headache patient. Routine
      diagnosis employing cerebrospinal fluid analysis can be abandoned when excluding
      subarachnoid hemorrhage in a patient with headache symptoms, if blood is with
      certainty not observed in the CT scan of the head and no more than six hours have
      passed after the onset of the symptom. If subarachnoid hemorrhage is detected,
      cerebral CT angiography will be performed at the same time and a neurosurgeon
      consulted about the need of operative treatment.

PMID- 29190052
TI  - Clinical picture and overall status of newly diagnosed HIV patients at Turku
      University Hospital in 2013.
AB  - Our patient material consists of the 12 patients diagnosed during one year. In
      all cases, sex was the likely mode of transmission, the number of partners having
      been high for some patients. Some of the cases were originally detected as a
      result of contact tracing. In two patients the disease had already at the time of
      diagnosis progressed to the AIDS stage, naturally complicating the initial phase
      of treatment. In a quarter of our patients the disease could have been discovered
      earlier from the symptoms of the primary infection, provided that testing had
      been done. Adherence to treatment in a HIV patient and treatment outcome are
      usually excellent.

PMID- 29190053
TI  - Ectopic pregnancy after supracervical hysterectomy.
AB  - Ectopic pregnancy after hysterectomy is a rare but potentially life-threatening
      condition. If ovaries are present, ectopic pregnancy should be ruled out in women
      with acute abdominal pain and history of hysterectomy. Our patient had an ectopic
      pregnancy six months after supracervical hysterectomy.

PMID- 29190054
TI  - Cancer of the tongue - early detection improves the prognosis.
AB  - Approximately 30 to 40% of all patients with tongue cancer still succumb to the
      disease in five years. Early diagnosis of the disease is of vital importance,
      because treatment will in that case cause considerably less harm. The diagnosis
      is confirmed with a histological specimen, which should be taken from every
      suspicious lesion, and can easily be taken under local anesthesia with a punch.
      Already when seeking treatment, as many as 25 % of patients with tongue cancer
      have neck metastases, which influence the prognosis. Heavy use of tobacco and
      alcohol are the most important risk factors of tongue cancer.

PMID- 29190055
TI  - Help from habit reversal for supragastric belching.
AB  - Supragastric belching differs from common gastric belching. It can be detected by
      24-hour intra-esophageal impedance monitoring. Belching is seldom the only
      symptom: reflux symptom is present in 95% and dysphagia in 65% of the patients.
      In supragastric belching, the air does not come from the stomach but instead from
      the esophagus. Belching is caused by the patient him/herself swallowing air into
      the esophagus. This voluntary but unconscious symptom is treated by therapy in
      which explaining the mechanism of belching for the patient and learning of
      correct diaphragmatic breathing technique play a central role. Habit reversal is
      utilized for teaching the patient to react correctly to preemptive symptoms.

PMID- 29190056
TI  - Gunshot wounds in Finland.
AB  - On average 200 gunshot wounds are treated in Finland annually. Half of them are
      caused by firearm accidents, whereas the great majority of fatal wounds are self
      inflicted. Physicians treating trauma patients should be familiar with the basics
      of ballistics. In practice, however, a distinction between gunshot wounds caused
      by handguns and those caused by rifles or shotguns is generally sufficient.
      Generally accepted guidelines for treating trauma patients are followed, and
      imaging is used for nearly all patients. Removal of bullets is generally not
      necessary. Most patients require operative treatment, but in certain cases a non
      operative approach may be considered. In severe gunshot wounds rapidly
      administered antibiotics and a sufficiently radical debridement remain the
      mainstays of treatment.

PMID- 29190057
TI  - Altered role of the concept of psychopathy in forensic psychiatry.
AB  - During the early 20th century, psychopathy referred to "borderland states"
      between normality and mental illness, corresponding to the current personality
      disorders. In psychiatric assessment, a significant proportion of psychopaths
      were considered to be not of sound mind, i.e. of diminished responsibility in
      contemporary language, which in most cases also led to shorter punishments.
      Psychopathy as diagnosis was abandoned in 1969, after which use has been made of
      the terms disorders of character and, later on, personality disorders. Nowadays,
      personality disorders can have a punishment-shortening effect only if they come
      close to a psychotic disorder. A psychopathy assessed by using current methods
      may even result in a longer verdict.

PMID- 29190058
TI  - Diagnosis of nonalcoholic fatty liver disease (NAFLD).
AB  - Nonalcoholic fatty liver disease (NAFLD) increases mortality from liver and heart
      disease and is the most important cause of hepatocellular carcinoma (HCC), which
      is rapidly becoming more common. Those having an increased fibrosis risk,
      cirrhosis or HCC should be identified amongst those with simple steatosis. Liver
      enzymes should always be determined at the yearly follow-up of patients with type
      2 diabetes and those with the metabolic syndrome. Fatty liver should lead to an
      assessment of the risk of fibrosis by using a simple fibrosis test and to the
      referral of patients at risk by a specialist for diagnosis and treatment of NASH
      and fibrosis. NASH can only be diagnosed using a liver biopsy.

PMID- 29190059
TI  - Lasers in corneal surgery.
AB  - New laser methods have introduced new possibilities and partly replaced
      traditional methods in corneal surgery. Femtosecond lasers have traditionally
      been used to replace the surgeons' knife in corneal refractive surgery and
      corneal transplantation. Excimer laser has been used from the beginning of 1990
      for the reshaping of cornea. With the development of excimer laser, traditional
      photorefractive corneal surgery has improved and new methods have been found such
      as PRK, PTK, epi-LASIK, and LASEK. Today LASIK, the most commonly used refractive
      surgery, uses both femtosecond and excimer lasers. SMILE, the most recent method
      in corneal refractive surgery, is solely based on the use of femtosecond laser.

PMID- 29190060
TI  - The long read t recovery: treatment outcome and cost among adolescents treated
      for anorexia nervosa in specialized care.
AB  - NTRODUCTION: We investigated factors affecting treatment outcome and cost of
      treatment among adolescents treated for anorexia nervosa in specialized care.
      METHODS: Records of 47 patients with anorexia nervosa treated at the adolescent
      eating disorder unit were reviewed retrospectively. RESULTS: Individual
      differences in the need for treatment and cost of treatment were considerable.
      Nearly one third of patients required treatment at multiple wards in addition to
      outpatient care. The majority of costs (76%) incurred from treating a minority
      (29 %) of patients. Psychiatric comorbidity, particularly depression, was
      associated with a greater need for treatment and higher costs. CONCLUSIONS: The
      cost of treatment of anorexia nervosa is considerable, but many of those
      requiring intensive treatment have a favorable outcome.

PMID- 29190064
TI  - Investigation of (Leaky) ALD TiO2 Protection Layers for Water-Splitting
      Photoelectrodes.
AB  - Protective overlayers for light absorbers in photoelectrochemical water-splitting
      devices have gained considerable attention in recent years. They stabilize light
      absorbers which would normally be prone to chemical side reactions leading to
      degradation of the absorber. Atomic layer deposition (ALD) enables conformal and
      reproducible ultrathin protective layer growth even on highly structured
      substrates. One of the most widely investigated protective layers is amorphous
      TiO2, deposited by ALD at a relatively low temperature (120-150  degrees C). We
      have deposited protective layers from tetrakis(dimethylamido)titanium(IV) at two
      different temperatures and investigated their chemical composition as well as
      optical and electrochemical properties. Our main findings reveal a change in the
      flat band potential with thickness, reaching a stable value of about -50 to -100
      mV versus reversible hydrogen electrode for films >30 nm, with doping densities
      of ~1020 cm3. Practical thicknesses to achieve pinhole-free films are evaluated
      and discussed.

PMID- 29190065
TI  - Effects of Inserting Thiophene as a pi-Bridge on the Properties of Naphthalene
      Diimide-alt-Fused Thiophene Copolymers.
AB  - On the basis of naphthalene diimide (NDI) units connected to thiophene (T),
      thienothiophene (TT), or dithienothiophene (DTT) units via a thiophene pi-bridge,
      three new copolymers-PDTNDI-T, PDTNDI-TT, and PDTNDI-DTT, respectively-were
      synthesized and used in the fabrication of all-polymer solar cells (all-PSCs).
      The relationships between the structures of the polymers and their optoelectronic
      properties and photovoltaic performances as electron acceptors in all-PSCs were
      investigated in detail. As the number of copolymerized heteroaromatic rings in
      the DTNDI-based polymers increased, the power conversion efficiencies of the
      resulting all-PSCs were found to decrease. This decreasing trend in the
      photovoltaic performance is opposite to the results reported previously for NDI
      based polymers lacking the thiophene pi-bridge and naphthodithiophene diimide
      based polymers. In addition, the three polymers were found to exhibit distinct
      molecular orientations: a face-on orientation for PDTNDI-T and edge-on
      orientations for PDTNDI-TT and PDTNDI-DTT. Our results indicate that large fused
      aromatic rings are not necessarily advantageous in the design of NDI-based
      polymers containing pi-conjugated bridges.

PMID- 29190066
TI  - Micropore Geometry Manipulation by Macroscopic Deformation Based on Shape Memory
      Effect in Porous PLLA Membrane and its Enhanced Separation Performance.
AB  - An effective strategy to tailor the microporous structures has been developed
      based on the shape memory effect in porous poly(l-lactic acid) membranes in which
      tiny crystals and amorphous matrix play the roles of shape-fixed phase and
      reversible-phase, respectively. Our results indicate that not only PLLA membranes
      but micropores exhibit shape memory properties. The proportional deformations on
      two scales have been achieved by uniaxial or biaxial tension, providing a facile
      way to manipulate continuously the size and the orientation degree of pores on
      microscale. The enhanced separation performance has been validated by taking
      polystyrene colloids with varying diameters as an example.

PMID- 29190067
TI  - Matrix Sputtering Method: A Novel Physical Approach for Photoluminescent Noble
      Metal Nanoclusters.
AB  - Noble metal nanoclusters are believed to be the transition between single metal
      atoms, which show distinct optical properties, and metal nanoparticles, which
      show characteristic plasmon absorbance. The interesting properties of these
      materials emerge when the particle size is well below 2 nm, such as
      photoluminescence, which has potential application particularly in biomedical
      fields. These photoluminescent ultrasmall nanoclusters are typically produced by
      chemical reduction, which limits their practical application because of the
      inherent toxicity of the reagents used in this method. Thus, alternative
      strategies are sought, particularly in terms of physical approaches, which are
      known as "greener alternatives," to produce high-purity materials at high yields.
      Thus, a new approach using the sputtering technique was developed. This method
      was initially used to produce thin films using solid substrates; now it can be
      applied even with liquid substrates such as ionic liquids or polyethylene glycol
      as long as these liquids have a low vapor pressure. This revolutionary
      development has opened up new areas of research, particularly for the synthesis
      of colloidal nanoparticles with dimensions below 10 nm. We are among the first to
      apply the sputtering technique to the physical synthesis of photoluminescent
      noble metal nanoclusters. Although typical sputtering systems have relied on the
      effect of surface composition and viscosity of the liquid matrix on controlling
      particle diameters, which only resulted in diameters ca. 3-10 nm, that were all
      plasmonic, our new approach introduced thiol molecules as stabilizers inspired
      from chemical methods. In the chemical syntheses of metal nanoparticles,
      controlling the concentration ratio between metal ions and stabilizing reagents
      is a possible means of systematic size control. However, it was not clear whether
      this would be applicable in a sputtering system. Our latest results showed that
      we were able to generically produce a variety of photoluminescent monometallic
      nanoclusters of Au, Ag, and Cu, all of which showed stable emission in both
      solution and solid form via our matrix sputtering method with the induction of
      cationic-, neutral-, and anionic-charged thiol ligands. We also succeeded in
      synthesizing photoluminescent bimetallic Au-Ag nanoclusters that showed tunable
      emission within the UV-NIR region by controlling the composition of the atomic
      ratio by a double-target sputtering technique. Most importantly, we have revealed
      the formation mechanism of these unique photoluminescent nanoclusters by
      sputtering, which had relatively larger diameters (ca. 1-3 nm) as determined
      using TEM and stronger emission quantum yield (max. 16.1%) as compared to typical
      photoluminescent nanoclusters prepared by chemical means. We believe the high
      tunability of sputtering systems presented here has significant advantages for
      creating novel photoluminescent nanoclusters as a complementary strategy to
      common chemical methods. This Account highlights our journey toward understanding
      the photophysical properties and formation mechanism of photoluminescent noble
      metal nanoclusters via the sputtering method, a novel strategy that will
      contribute widely to the body of scientific knowledge of metal nanoparticles and
      nanoclusters.

PMID- 29190069
TI  - Surface-Plasmon-Driven Hot Electron Photochemistry.
AB  - Visible-light-driven photochemistry has continued to attract heightened interest
      due to its capacity to efficiently harvest solar energy and its potential to
      solve the global energy crisis. Plasmonic nanostructures boast broadly tunable
      optical properties coupled with catalytically active surfaces that offer a unique
      opportunity for solar photochemistry. Resonant optical excitation of surface
      plasmons produces energetic hot electrons that can be collected to facilitate
      chemical reactions. This review sums up recent theoretical and experimental
      approaches for understanding the underlying photophysical processes in hot
      electron generation and discusses various electron-transfer models on both
      plasmonic metal nanostructures and plasmonic metal/semiconductor
      heterostructures. Following that are highlights of recent examples of plasmon
      driven hot electron photochemical reactions within the context of both cases. The
      review concludes with a discussion about the remaining challenges in the field
      and future opportunities for addressing the low reaction efficiencies in hot
      electron-induced photochemistry.

PMID- 29190068
TI  - Structural and Functional Basis for Targeting Campylobacter jejuni Agmatine
      Deiminase To Overcome Antibiotic Resistance.
AB  - Campylobacter jejuni is the most common bacterial cause of gastroenteritis and a
      major contributor to infant mortality in the developing world. The increasing
      incidence of antibiotic-resistant C. jejuni only adds to the urgency to develop
      effective therapies. Because of the essential role that polyamines play,
      particularly in protection from oxidative stress, enzymes involved in the
      biosynthesis of these metabolites are emerging as promising antibiotic targets.
      The recent description of an alternative pathway for polyamine synthesis,
      distinct from that in human cells, in C. jejuni suggests this pathway could be a
      target for novel therapies. To that end, we determined X-ray crystal structures
      of C. jejuni agmatine deiminase (CjADI) and demonstrated that loss of CjADI
      function contributes to antibiotic sensitivity, likely because of polyamine
      starvation. The structures provide details of key molecular features of the
      active site of this protein. Comparison of the unliganded structure (2.1 A
      resolution) to that of the CjADI-agmatine complex (2.5 A) reveals significant
      structural rearrangements that occur upon substrate binding. The shift of two
      helical regions of the protein and a large conformational change in a loop near
      the active site generate a narrow binding pocket around the bound substrate. This
      change optimally positions the substrate for catalysis. In addition, kinetic
      analysis of this enzyme demonstrates that CjADI is an iminohydrolase that
      effectively deiminates agmatine. Our data suggest that C. jejuni agmatine
      deiminase is a potentially important target for combatting antibiotic resistance,
      and these results provide a valuable framework for guiding future drug
      development.

PMID- 29190070
TI  - Comment on "Direct Monitoring of Exogenous gamma-Hydroxybutyric Acid in Body
      Fluids by NMR Spectroscopy": Several Issues to Consider When Quantifying gamma
      Hydroxybutyric Acid in Biological Matrixes.

PMID- 29190071
TI  - Atomic-Scale Origin of the Quasi-One-Dimensional Metallic Conductivity in
      Strontium Niobates with Perovskite-Related Layered Structures.
AB  - The quasi-one-dimensional (1D) metallic conductivity of the perovskite-related
      SrnNbnO3n+2 compounds is of continuing fundamental physical interest as well as
      being important for developing advanced electronic devices. The SrnNbnO3n+2
      compounds can be derived by introducing additional oxygen into the SrNbO3
      perovskite. However, the physical origin for the transition of electrical
      properties from the three-dimensional (3D) isotropic conductivity in SrNbO3 to
      the quasi-1D metallic conductivity in SrnNbnO3n+2 requires more in-depth
      clarification. Here we combine advanced transmission electron microscopy with
      atomistic first-principles calculations to unambiguously determine the atomic and
      electronic structures of the SrnNbnO3n+2 compounds and reveal the underlying
      mechanism for their quasi-1D metallic conductivity. We demonstrate that the local
      electrical conductivity in the SrnNbnO3n+2 compounds directly depends on the
      configuration of the NbO6 octahedra in local regions. These findings will shed
      light on the realization of two-dimensional (2D) electrical conductivity from a
      bulk material, namely by segmenting a 3D conductor into a stack of 2D conducting
      thin layers.

PMID- 29190072
TI  - Quantification of DNA in Neonatal Dried Blood Spots by Adenine Tandem Mass
      Spectrometry.
AB  - Newborn screening programs have expanded to include molecular-based assays as
      first-tier tests and the success of these assays depends on the quality and yield
      of DNA extracted from neonatal dried blood spots (DBS). To meet high throughput
      and rapid turnaround time requirements, newborn screening laboratories adopted
      rapid DNA extraction methods that produce crude extracts. Quantification of DNA
      in neonatal DBS is not routinely performed due to technical challenges; however,
      this may enhance the performance of assays that are sensitive to amounts of input
      DNA. In this study, we developed a novel high throughput method to quantify total
      DNA in DBS. It is based on specific acid-catalyzed depurination of DNA followed
      by mass spectrometric quantification of adenine. The amount of adenine was used
      to calculate DNA quantity per 3.2 mm DBS. Reference intervals were established
      using archived, neonatal DBS (n = 501) and a median of 130.6 ng of DNA per DBS
      was obtained, which is in agreement with literature values. The intra- and
      interday variations were <15%. The limits of detection and quantification were
      12.5 and 37.8 nmol/L adenine, respectively. We demonstrated that DNA from
      neonatal DBS can be successfully quantified in high throughput settings using
      instruments currently deployed in NBS laboratories.

PMID- 29190073
TI  - Response to Comment on "Direct Monitoring of Exogenous gamma-Hydroxybutyric Acid
      in Body Fluids by NMR Spectroscopy": Several Issues to Consider When Quantifying
      gamma-Hydroxybutyric Acid in Biological Matrixes.

PMID- 29190074
TI  - Carbon Nanotube Embedded Nanostructure for Biometrics.
AB  - Low electric energy loss is a very important problem to minimize the decay of
      transferred energy intensity due to impedance mismatch. This issue has been dealt
      with by adding an impedance matching layer at the interface between two media. A
      strategy was proposed to improve the charge transfer from the human body to a
      biometric device by using an impedance matching nanostructure. Nanocomposite
      pattern arrays were fabricated with shape memory polymer and carbon nanotubes.
      The shape recovery ability of the nanopatterns enhanced durability and
      sustainability of the structure. It was found that the composite nanopatterns
      improved the current transfer by two times compared with the nonpatterned
      composite sample. The underlying mechanism of the enhanced charge transport was
      understood by carrying out a numerical simulation. We anticipate that this study
      can provide a new pathway for developing advanced biometric devices with high
      sensitivity to biological information.

PMID- 29190075
TI  - Supramolecularly Caged Green-Emitting Ionic Ir(III)-Based Complex with
      Fluorinated C^N Ligands and Its Application in Light-Emitting Electrochemical
      Cells.
AB  - Ionic Ir(III) complexes are the most promising emitters in light emitting
      electrochemical cells (LECs), especially in the high energy emission range for
      which it is difficult to find emitters with sufficient efficiencies and
      lifetimes. To overcome this challenge, we introduced the concept of
      intramolecular pi-pi stacking of an ancillary ligand (6-phenyl-2,2'-bipyridine,
      pbpy) in the design of a new green-emitting iridium ionic transition metal
      complex with a fluoro-substituted cyclometallated ligand, 2-(4
      fluorophenyl)pyridinato (4Fppy). [Ir(4Fppy)2(pbpy)][PF6] has been synthesized and
      characterized and its photophysical and electrochemical properties have been
      studied. The complex emits green light with maxima at 561 and 556 nm under UV
      excitation from powder and thin film, respectively, and displays a high
      photoluminescence quantum yield (PLQY) of 78.5%. [Ir(4Fppy)2(pbpy)][PF6] based
      LECs driven under pulsed current conditions showed under an average current
      density of 100 A m-2 (at 50% duty cycle) a maximum luminance of 1443 cd m-2,
      resulting in 14.4 cd A-1 and 7.4 lm W-1 current and power efficiencies,
      respectively. A remarkable long device lifetime of 214 h was observed. Reducing
      the average current density to 18.5 A m-2 (at 75% duty cycle) led to an
      exceptional device performance of 19.3 cd A-1 and 14.4 lm W1- for current and
      power efficiencies, an initial maximum luminance of 352 cd m-2 and a lifetime of
      617 h.

PMID- 29190076
TI  - A Reversible, Charge-Induced Intramolecular C4a-S-Cysteinyl-Flavin in Choline
      Oxidase Variant S101C.
AB  - Choline oxidase serves as a paradigm for alcohol oxidation catalyzed by flavin
      dependent enzymes. In its active site, S101 is 4 A from the flavin C4a atom on an
      extended loop. Enzyme variants substituted at S101 were generated in a previous
      study and investigated mechanistically [Yuan, H., and Gadda, G. (2011)
      Biochemistry 50, 770-779]. In this study, the typical ultraviolet-visible (UV
      vis) absorption spectrum of oxidized flavin was observed for the S101C enzyme in
      HEPES, TES, or sodium phosphate, whereas an absorption spectrum suggesting the
      presence of a C4a-flavin adduct with cysteine was obtained in Tris-HCl at pH 8.0.
      pH titrations of the UV-vis absorption spectrum of the wild-type, S101A, S101C,
      and H99N enzymes in the presence and absence of Tris allowed for the
      determination of two pKa values that define a pH range in which the C4a-S
      cysteinyl flavin is stabilized. Inhibition studies and stopped-flow kinetics
      demonstrated that binding of protonated Tris in the active site of the S101C
      enzyme is required to form the C4a-S-cysteinyl flavin. Deuterium kinetic isotope
      effects and proton inventories of the S101C enzyme mixed in a stopped-flow
      spectrophotometer with Tris established a mechanism for the reversible formation
      of the C4a-S-cysteinyl flavin. This study provides a detailed mechanistic
      analysis of the reversible formation of a bicovalent C4a-S-cysteinyl-8alpha-N3
      histidyl flavin in choline oxidase, identifying an optimal pH range and a
      mechanistic rationale for the stabilization of de novo C4a-S-cysteinyl-flavins.
      Moreover, it presents an example of an intramolecular reaction of an enzyme-bound
      flavin without a substrate.

PMID- 29190077
TI  - Evaluation of Matrix Metalloproteinase Inhibition by Peptide Microarray-Based
      Fluorescence Assay on Polymer Brush Substrate and in Vivo Assessment.
AB  - Matrix metalloproteinases (MMPs) are important biomarkers and potential
      therapeutic targets of tumor. In this report, a peptide microarray-based
      fluorescence assay is developed for MMPs inhibitors evaluation through
      immobilization of biotin-modified peptides on the poly(glycidyl methacrylate-co-2
      hydroxyethyl methacrylate) (P(GMA-HEMA)) brush-modified glass slides. After
      biotin is recognized with cyanine 3 (Cy3)-modified avidin (Cy3-avidin), the
      microarrays can produce strong fluorescence signal. The biotin moieties detach
      from microarray, when the biotin-modified peptide substrates are specially
      cleaved by a MMP, resulting in decreased fluorescence intensity of the
      microarray. The decreasing level of fluorescence intensity is correlated with the
      MMP inhibition. Nine known MMP inhibitors against MMP-2 and MMP-9 are evaluated
      by the assay, and the quantitative determination of inhibitory potencies (half
      maximal inhibitory concentration) are obtained, which are comparable with the
      literatures. Two biocompatible fluorogenic peptides containing MMP-specific
      recognition sequences and FAM/Dabcyl fluorophore-quencher pair are designed as
      activatable reporter probes for sensing MMP-2 and MMP-9 activities in cell and in
      vivo. The peptide microarray-based results are well verified by the cell
      inhibition assay and in vitro fluorescence imaging, and further confirmed by the
      in vivo imaging of HT-1080 tumor-bearing mice.

PMID- 29190079
TI  - Incorporation of Europium(III) into Scheelite-Related Host Matrixes ABO4 (A =
      Ca2+, Sr2+, Ba2+; B = W6+, Mo6+): Role of A and B Sites on the Dopant Site
      Distribution and Photoluminescence.
AB  - Scheelite- and powellite-related materials doped with trivalent lanthanides or
      actinides have been the subject of extensive research due to their important role
      in mineralogical, technological, and environmental implications. Detailed
      structural knowledge of these solid solutions is essential for understanding
      their physicochemical properties and predicting material properties. In this
      work, we conduct a comprehensive spectroscopic analysis by means of polarization
      dependent site-selective time-resolved laser-induced fluorescence spectroscopy,
      to delineate the influence of the host phase cations for a series of scheelite
      type matrixes based on a general formula of ABO4 (A = Ca2+, Sr2+, Ba2+; B = W6+,
      Mo6+) on the local environment of the Eu3+ dopant. Eu3+ has been used as a
      luminescent probe to access the local structural environment of crystalline
      substitutional sites suitable for trivalent lanthanide or actinide occupation.
      Our results show that the lattice distortion is overall minor, but increases with
      increasing mismatch of host and guest cation size. We observe a linear dependence
      of Eu3+'s excitation energy on the host cation size and the A-O bond distance,
      which can be used to determine the hitherto unknown Eu-O bond distance in
      NaEu(WO4)2. A value of 2.510 A was determined, somewhat larger than a previously
      reported number for NaEu(MoO4)2. The results also show clear evidence that the
      local coordination environment of Eu3+ in WO42- materials is more symmetrical
      than in their isostructural MoO42- counterparts. The detailed spectroscopic
      interpretation conducted in this study resolves the relation between local
      distortion around a dopant and the host phase cations in structural disordered
      materials and may give novel insights with respect to rational design and
      tailoring of functional materials.

PMID- 29190078
TI  - Cu(II) Binding to the Peptide Ala-His-His, a Chimera of the Canonical Cu(II)
      Binding Motifs Xxx-His and Xxx-Zzz-His.
AB  - Peptides and proteins with the N-terminal motifs NH2-Xxx-His and NH2-Xxx-Zzz-His
      form well-established Cu(II) complexes. The canonical peptides are Gly-His-Lys
      and Asp-Ala-His-Lys (from the wound healing factor and human serum albumin,
      respectively). Cu(II) is bound to NH2-Xxx-His via three nitrogens from the
      peptide and an external ligand in the equatorial plane (called 3N form here). In
      contrast, Cu(II) is bound to NH2-Xxx-Zzz-His via four nitrogens from the peptide
      in the equatorial plane (called 4N form here). These two motifs are not mutually
      exclusive, as the peptides with the sequence NH2-Xxx-His-His contain both of
      them. However, this chimera has never been fully explored. In this work, we use a
      multispectroscopic approach to analyze the Cu(II) binding to the chimeric peptide
      Ala-His-His (AHH). AHH is capable of forming the 3N- and 4N-type complexes in a
      pH dependent manner. The 3N form predominates at pH ~ 4-6.5 and the 4N form at ~
      pH 6.5-10. NMR experiments showed that at pH 8.5, where Cu(II) is almost
      exclusively bound in the 4N form, the Cu(II)-exchange between AHH or the amidated
      AHH-NH2 is fast, in comparison to the nonchimeric 4N form (AAH). Together, the
      results show that the chimeric AHH can access both Cu(II) coordination types,
      that minor changes in the second (or further) coordination sphere can impact
      considerably the equilibrium between the forms, and that Cu kinetic exchange is
      fast even when Cu-AHH is mainly in the 4N form.

PMID- 29190080
TI  - Ru-Complex Framework toward Aerobic Oxidative Transformations of beta
      Diketiminate and alpha-Ketodiimine.
AB  - The impact of the {Ru(acac)2} (acac- = acetylacetonate) framework on the
      transformations of C-H and C-H/C-C bonds of coordinated beta-diketiminate and
      ketodiimine scaffolds, respectively, has been addressed. It includes the
      following transformations involving {Ru(acac)2} coordinated beta-diketiminate in
      1 and ketodiimine in 2 with the simultaneous change in metal oxidation state: (i)
      insertion of oxygen into the C(sp2)-H bond of beta-diketiminate in 1, leading to
      the metalated ketodiimine in 2 and (ii) Bronsted acid (CH3COOH) assisted cleavage
      of unstrained C(sp2)-C(sp2)/C?N bonds of chelated ketodiimine (2) with the
      concomitant formation of intramolecular C-N bond in 3, as well as insertion of
      oxygen into the C(sp3)-H bond of 2 to yield -CHO function in 4 (-CH3 -> -CHO).
      The aforesaid transformation processes have been authenticated via structural
      elucidation of representative complexes and spectroscopic and electrochemical
      investigations.

PMID- 29190081
TI  - Suppression of Magnetic Quantum Tunneling in a Chiral Single-Molecule Magnet by
      Ferromagnetic Interactions.
AB  - Single-molecule magnets (SMMs) retain a magnetization without applied magnetic
      field for a decent time due to an energy barrier U for spin-reversal. Despite the
      success to increase U, the difficult to control magnetic quantum tunneling often
      leads to a decreased effective barrier Ueff and a fast relaxation. Here, we
      demonstrate the influence of the exchange coupling on the tunneling probability
      in two heptanuclear SMMs hosting the same spin-system with the same high spin
      ground state St = 21/2. A chirality-induced symmetry reduction leads to a switch
      of the MnIII-MnIII exchange from antiferromagnetic in the achiral SMM
      [MnIII6CrIII]3+ to ferromagnetic in the new chiral SMM RR[MnIII6CrIII]3+.
      Multispin Hamiltonian analysis by full-matrix diagonalization demonstrates that
      the ferromagnetic interactions in RR[MnIII6CrIII]3+ enforce a well-defined St =
      21/2 ground state with substantially less mixing of MS substates in contrast to
      [MnIII6CrIII]3+ and no tunneling pathways below the top of the energy barrier.
      This is experimentally verified as Ueff is smaller than the calculated energy
      barrier U in [MnIII6CrIII]3+ due to tunneling pathways, whereas Ueff equals U in
      RR[MnIII6CrIII]3+ demonstrating the absence of quantum tunneling.

PMID- 29190083
TI  - Structure-Based Design of 6-Chloro-4-aminoquinazoline-2-carboxamide Derivatives
      as Potent and Selective p21-Activated Kinase 4 (PAK4) Inhibitors.
AB  - Herein, we report the discovery and characterization of a novel class of PAK4
      inhibitors with a quinazoline scaffold. Based on the shape and chemical
      composition of the ATP-binding pocket of PAKs, we chose a 2,4-diaminoquinazoline
      series of inhibitors as a starting point. Guided by X-ray crystallography and a
      structure-based drug design (SBDD) approach, a series of novel 4-aminoquinazoline
      2-carboxamide PAK4 inhibitors were designed and synthesized. The inhibitors'
      selectivity, therapeutic potency, and pharmaceutical properties were optimized.
      One of the best compounds, 31 (CZh226), showed remarkable PAK4 selectivity (346
      fold vs PAK1) and favorable kinase selectivity profile. Moreover, this compound
      potently inhibited the migration and invasion of A549 tumor cells by regulating
      the PAK4-directed downstream signaling pathways in vitro. Taken together, these
      data support the further development of 31 as a lead compound for PAK4-targeted
      anticancer drug discovery and as a valuable research probe for the further
      biological investigation of group II PAKs.

PMID- 29190082
TI  - Pourbaix Diagram, Proton-Coupled Electron Transfer, and Decay Kinetics of a
      Protein Tryptophan Radical: Comparing the Redox Properties of W32* and Y32*
      Generated Inside the Structurally Characterized alpha3W and alpha3Y Proteins.
AB  - Protein-based "hole" hopping typically involves spatially arranged redox-active
      tryptophan or tyrosine residues. Thermodynamic information is scarce for this
      type of process. The well-structured alpha3W model protein was studied by protein
      film square wave voltammetry and transient absorption spectroscopy to obtain a
      comprehensive thermodynamic and kinetic description of a buried tryptophan
      residue. A Pourbaix diagram, correlating thermodynamic potentials (E degrees ')
      with pH, is reported for W32 in alpha3W and compared to equivalent data recently
      presented for Y32 in alpha3Y ( Ravichandran , K. R. ; Zong , A. B. ; Taguchi , A.
      T. ; Nocera , D. G. ; Stubbe , J. ; Tommos , C. J. Am. Chem. Soc. 2017 , 139 ,
      2994 - 3004 ). The alpha3W Pourbaix diagram displays a pKOX of 3.4, a E degrees
      '(W32(N*+/NH)) of 1293 mV, and a E degrees '(W32(N*/NH); pH 7.0) of 1095 +/- 4 mV
      versus the normal hydrogen electrode. W32(N*/NH) is 109 +/- 4 mV more oxidizing
      than Y32(O*/OH) at pH 5.4-10. In the voltammetry measurements, W32 oxidation
      reduction occurs on a time scale of about 4 ms and is coupled to the release and
      subsequent uptake of one full proton to and from bulk. Kinetic analysis further
      shows that W32 oxidation likely involves pre-equilibrium electron transfer
      followed by proton transfer to a water or small water cluster as the primary
      acceptor. A well-resolved absorption spectrum of W32* is presented, and analysis
      of decay kinetics show that W32* persists ~104 times longer than aqueous W* due
      to significant stabilization by the protein. The redox characteristics of W32 and
      Y32 are discussed relative to global and local protein properties.

PMID- 29190084
TI  - Acovenoside A Induces Mitotic Catastrophe Followed by Apoptosis in Non-Small-Cell
      Lung Cancer Cells.
AB  - We investigated the cytotoxic potential of the cardenolide glycoside acovenoside
      A against non-small-cell lung cancer cells. Lung cancer is the leading cause of
      cancer-related mortality and the second most common cancer diagnosed.
      Epidemiological studies revealed a direct correlation between the regular
      administration of cardiac glycosides and a lower incidence of various cancers.
      Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently
      inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung
      cancer cells with an IC50 of 68 +/- 3 nM after 48 h of exposure. Compared to the
      antineoplastic agent doxorubicin, acovenoside A was more potent in inhibiting the
      viability of A549 cancer cells. Moreover, acovenoside A exhibited selectivity
      against cancer cells, being significantly less toxic to lung fibroblasts and
      nontoxic for peripheral blood mononuclear cells. Analysis of the cell cycle
      profile in acovenoside A-treated A549 cells revealed mitotic arrest, due to
      accumulation of the G2/M regulators cyclin B1 and CDK1, and cytokinesis failure.
      Furthermore, acovenoside A affected the mitochondrial membrane integrity and
      induced production of radical oxygen species, which resulted in induction of
      canonical apoptosis, manifested by caspase 3 activation and DNA fragmentation.
      Based on our results, acovenoside A warrants further exploration as a potential
      anticancer lead.

PMID- 29190085
TI  - High-Confidence Protein-Ligand Complex Modeling by NMR-Guided Docking Enables
      Early Hit Optimization.
AB  - Structure-based drug design is an integral part of modern day drug discovery and
      requires detailed structural characterization of protein-ligand interactions,
      which is most commonly performed by X-ray crystallography. However, the success
      rate of generating these costructures is often variable, in particular when
      working with dynamic proteins or weakly binding ligands. As a result, structural
      information is not routinely obtained in these scenarios, and ligand optimization
      is challenging or not pursued at all, representing a substantial limitation in
      chemical scaffolds and diversity. To overcome this impediment, we have developed
      a robust NMR restraint guided docking protocol to generate high-quality models of
      protein-ligand complexes. By combining the use of highly methyl-labeled protein
      with experimentally determined intermolecular distances, a comprehensive set of
      protein-ligand distances is generated which then drives the docking process and
      enables the determination of the correct ligand conformation in the bound state.
      For the first time, the utility and performance of such a method is fully
      demonstrated by employing the generated models for the successful, prospective
      optimization of crystallographically intractable fragment hits into more potent
      binders.

PMID- 29190087
TI  - Task-Specific Scoring Functions for Predicting Ligand Binding Poses and Affinity
      and for Screening Enrichment.
AB  - Molecular docking, scoring, and virtual screening play an increasingly important
      role in computer-aided drug discovery. Scoring functions (SFs) are typically
      employed to predict the binding conformation (docking task), binding affinity
      (scoring task), and binary activity level (screening task) of ligands against a
      critical protein target in a disease's pathway. In most molecular docking
      software packages available today, a generic binding affinity-based (BA-based) SF
      is invoked for all three tasks to solve three different, but related, prediction
      problems. The limited predictive accuracies of such SFs in these three tasks has
      been a major roadblock toward cost-effective drug discovery. Therefore, in this
      work, we develop BT-Score, an ensemble machine-learning (ML) SF of boosted
      decision trees and thousands of predictive descriptors to estimate BA. BT-Score
      reproduced BA of out-of-sample test complexes with correlation of 0.825. Even
      with this high accuracy in the scoring task, we demonstrate that the docking and
      screening performance of BT-Score and other BA-based SFs is far from ideal. This
      has motivated us to build two task-specific ML SFs for the docking and screening
      problems. We propose BT-Dock, a boosted-tree ensemble model trained on a large
      number of native and computer-generated ligand conformations and optimized to
      predict binding poses explicitly. This model has shown an average improvement of
      25% over its BA-based counterparts in different ligand pose prediction scenarios.
      Similar improvement has also been obtained by our screening-based SF, BT-Screen,
      which directly models the ligand activity labeling task as a classification
      problem. BT-Screen is trained on thousands of active and inactive protein-ligand
      complexes to optimize it for finding real actives from databases of ligands not
      seen in its training set. In addition to the three task-specific SFs, we propose
      a novel multi-task deep neural network (MT-Net) that is trained on data from the
      three tasks to simultaneously predict binding poses, affinities, and activity
      levels. We show that the performance of MT-Net is superior to conventional SFs
      and on a par with or better than models based on single-task neural networks.

PMID- 29190086
TI  - DNA Damage Emanating From a Neutral Purine Radical Reveals the Sequence Dependent
      Convergence of the Direct and Indirect Effects of gamma-Radiolysis.
AB  - Nucleobase radicals are the major intermediates generated by the direct (e.g.,
      dA*+) and indirect (e.g., dA*) effects of gamma-radiolysis. dA* was independently
      generated in DNA for the first time. The dA*+/dA* equilibrium, and consequently
      the reactivity in DNA, is significantly shifted toward the radical cation by a
      flanking dA. Tandem lesions emanating from dA* are the major products when the
      reactive intermediate is flanked by a 5'-dGT. In contrast, when dA* is flanked by
      dA, the increased dA*+ pKa results in DNA damage arising from hole transfer. This
      is the first demonstration that sequence effects lead to the intersection of the
      direct and indirect effects of ionizing radiation.

PMID- 29190088
TI  - Highly Effective Polyphosphate Synthesis, Phosphate Removal, and Concentration
      Using Engineered Environmental Bacteria Based on a Simple Solo Medium-Copy
      Plasmid Strategy.
AB  - Microbial polyphosphate (polyP) production is vital to the removal of phosphate
      from wastewater. However, to date, engineered polyP synthesis using genetically
      accessible environmental bacteria remains a challenge. This study develops a
      simple solo medium-copy plasmid-based polyphosphate kinase (PPK1) overexpression
      strategy for achieving maximum intracellular polyphosphate accumulation by
      environmental bacteria. The polyP content of the subsequently engineered
      Citrobacter freundii (CPP) could reach as high as 12.7% of its dry weight. The
      biomass yield of CPP was also guaranteed because of negligible metabolic burden
      effects resulting from the medium plasmid copy number. Consequently, substantial
      removal of phosphate (Pi) from the ambient environment was achieved
      simultaneously. Because of the need for exogenous Pi for in vivo ATP
      regeneration, CPP could thoroughly remove Pi from synthetic municipal wastewater
      when it was applied for the "one-step" removal of Pi with a bench-scale sequence
      batch membrane reactor. Almost all the phosphorus except for that assimilated by
      CPP for cellular growth could be recovered in the form of more concentrated Pi.
      Overall, engineering environmental bacteria to overexpress PPK1 via a solo medium
      copy plasmid strategy may represent a valuable general option for not only
      biotechnological research based on sufficient intracellular polyP production but
      also removal of Pi from wastewater and Pi enrichment.

PMID- 29190089
TI  - Lending an Eye to a Beleaguered Guardian of the Environment.

PMID- 29190090
TI  - External Exposure to Short- and Medium-Chain Chlorinated Paraffins for the
      General Population in Beijing, China.
AB  - Chlorinated paraffins (CPs) are a class of compounds that are currently produced
      and used in large amounts in commercial products worldwide. In this study, food,
      indoor air, indoor dust, and drinking water samples were collected to evaluate
      the external exposure levels of CPs and possible pathway for the general
      population in Beijing, China. Short chain CPs (SCCPs) and medium chain CPs
      (MCCPs) in 199 samples were analyzed using a gas chromatography tandem time-of
      flight high-resolution mass spectrometry (GC-TOF-HR-MS) method. High levels of
      CPs were observed in the indoor environment from residential houses, offices, and
      student dormitories. The geometric mean concentrations (GM) of ?SCCPs and ?MCCPs
      in indoor dust were 92 MUg g-1 and 82 MUg g-1, respectively, while in indoor air,
      the concentrations were 80 ng m-3 and 3.4 ng m-3, respectively. The GM of ?SCCPs
      and ?MCCPs in the diet were 83 ng g-1 dry weight (dw) and 56 ng g-1 dw,
      respectively. The most important external exposure routes to CPs to the general
      populations in Beijing were food intake and indoor dust ingestion. Indoor dust
      and indoor air posed higher risks for toddlers and infants than for adults.

PMID- 29190091
TI  - Pathways for Concerted [2 + 2] Cycloaddition to Cumulenes.
AB  - A computational search has revealed concerted pathways for [2 + 2] cycloaddition
      of ethylene to all 10 of the cumulenes with the formula X?C?Y, where X, Y = C, N,
      O, and S. Four different concerted pathways have been found, three of them
      pseudopericyclic plus another based on sp-hybridized carbon. In the case of 2 of
      the 16 possible cycloadditions, a pair of novel three-membered ring intermediates
      has been discovered. As simple model reactions, cycloaddition of ethylene to
      formaldehyde, thioformaldehyde, and formaldimine is also described.

PMID- 29190092
TI  - Structure-Based Design and Biological Characterization of Selective Histone
      Deacetylase 8 (HDAC8) Inhibitors with Anti-Neuroblastoma Activity.
AB  - Histone deacetylases (HDACs) are important modulators of epigenetic gene
      regulation and additionally control the activity of non-histone protein
      substrates. While for HDACs 1-3 and 6 many potent selective inhibitors have been
      obtained, for other subtypes much less is known on selective inhibitors and the
      consequences of their inhibition. The present report describes the development of
      substituted benzhydroxamic acids as potent and selective HDAC8 inhibitors.
      Docking studies using available crystal structures have been used for structure
      based optimization of this series of compounds. Within this study, we have
      investigated the role of HDAC8 in the proliferation of cancer cells and optimized
      hits for potency and selectivity, both in vitro and in cell culture. The
      combination of structure-based design, synthesis, and in vitro screening to
      cellular testing resulted in potent and selective HDAC8 inhibitors that showed
      anti-neuroblastoma activity in cellular testing.

PMID- 29190093
TI  - cis-Dioxorhenium(V/VI) Complexes Supported by Neutral Tetradentate N4 Ligands.
      Synthesis, Characterization, and Spectroscopy.
AB  - A series of cis-dioxorhenium(V) complexes containing chiral tetradentate N4
      ligands, including cis-[ReV(O)2(pyxn)]+ (1; pyxn = N,N'-dimethyl-N,N'-bis(2
      pyridylmethyl)cyclohexane-1,2-diamine), cis-[ReV(O)2(6-Me2pyxn)]+ (cis-2), cis
      [ReV(O)2(R,R-pdp)]+ (3; R,R-pdp = 1,1'-bis((R,R)-2-pyridinylmethyl)-2,2'
      bipyrrolidine), cis-[ReV(O)2(R,R-6-Me2pdp)]+ (4), and cis-[ReV(O)2(bqcn)]+ (5;
      bqcn = N,N'-dimethyl-N,N'-di(quinolin-8-yl)cyclohexane-1,2-diamine), were
      synthesized. Their structures were established by X-ray crystallography, showing
      Re-O distances in the range of 1.740(3)-1.769(8) A and O-Re-O angles of 121.4(2)
      124.8(4) degrees . Their cyclic voltammograms in MeCN (0.1 M [NBu4]PF6) display a
      reversible ReVI/V couple at E1/2 = 0.39-0.49 V vs SCE. In aqueous media, three
      proton-coupled electron transfer reactions corresponding to ReVI/V, ReV/III, and
      ReIII/II couples were observed at pH 1. The Pourbaix diagrams of 1.OTf, 3.OTf,
      and 5.OTf have been examined. The electronic absorption spectra of the cis
      dioxorhenium(V) complexes show three absorption bands at around 800 nm (600-1730
      dm3 mol-1 cm-1), 580 nm (1700-5580 dm3 mol-1 cm-1), and 462-523 nm (3170-6000 dm3
      mol-1 cm-1). Reaction of 1 with Lewis acids (or protic acids) gave cis
      [ReV(O)(OH)(pyxn)]2+ (1.H+), in which the Re-O distances are lengthened to
      1.788(5) A. Complex cis-2 resulted from isomerization of trans-2 at elevated
      temperature. cis-[ReVI(O)2(pyxn)](PF6)2 (1'.(PF6)2) was obtained by constant
      potential electrolysis of 1.PF6 in MeCN (0.1 M [NBu4]PF6) at 0.56 V vs SCE; it
      displays shorter Re-O distances (1.722(4), 1.726(4) A) and a smaller O-Re-O angle
      (114.88(18) degrees ) relative to 1 and shows a d-d transition absorption band at
      591 nm (epsilon = 77 dm3 mol-1 cm-1). With a driving force of ca. 75 kcal mol-1,
      1' oxidizes hydrocarbons with weak C-H bonds (75.5-76.3 kcal mol-1) via hydrogen
      atom abstraction. DFT and TDDFT calculations on the electronic structures and
      spectroscopic properties of the cis-dioxorhenium(V/VI) complexes were performed.

PMID- 29190094
TI  - Active Glucocorticoids Have a Range of Important Adverse Developmental and
      Physiological Effects on Developing Zebrafish Embryos.
AB  - Glucocorticoids in aquatic systems originating from natural excretion and medical
      use may pose a risk to fish. Here, we analyzed physiological and transcriptional
      effects of clobetasol propionate (CLO), cortisol and cortisone in zebrafish
      embryos as single compounds and binary mixtures. CLO and cortisol, but not
      cortisone showed a concentration-dependent decrease in muscle contraction,
      increase in heart rate, and accelerated hatching. CLO also induced immobilization
      and edema at high concentrations. Transcription analysis covering up to 26 genes
      showed that mostly genes related to glucose metabolism, immune system and
      development were differentially expressed at 91 ng/L and higher. CLO showed
      stronger effects on immune system genes than cortisol, which was characterized by
      upregulation of fkbp5, irg1l, gilz, and socs3, and development genes, matrix
      metalloproteinases mmp-9 and mmp-13, while cortisol led to stronger upregulation
      of the gluconeogenesis genes g6pca and pepck1. CLO also induced genes regulating
      the circadian rhythm, nr1d1 and per1a. In contrast, cortisone led to down
      regulation of vitellogenin. Binary mixtures of cortisol and CLO mostly showed a
      similar activity as CLO alone on physiological and transcriptional end points but
      additive effects in heart rate and pepck1 upregulation, which indicates that
      mixtures of glucocorticoids may be of concern for developing fish.

PMID- 29190096
TI  - Anisotropy in Time-Resolved Photoelectron Spectroscopy in the Gas Phase.
AB  - Transient absorption anisotropy is a well-established technique in time-resolved
      liquid phase spectroscopy. Here, we show how the technique is applied in the gas
      phase for time-resolved photoelectron spectroscopy and what type of additional
      information can be obtained as compared to other techniques. We exemplify its use
      by presenting results on rotational revivals in pyrazine after excitation at 324
      nm and provide new insights into two recent experiments: (i) the difference
      between Rydberg and valence state excitation after one- and two-photon absorption
      in butadiene and (ii) excitation to the two lowest lying vibronic modes of the
      degenerate pi3p Rydberg state in 1-azabicyclo[2.2.0]octane. Going forward, we
      expect the technique to be used on a regular basis, especially with the advent of
      high harmonic probe sources and liquid beam setups where other techniques to
      extract polarization-dependent information such as velocity map imaging cannot
      easily be applied.

PMID- 29190097
TI  - Stick-Slip Instabilities for Interfacial Chemical Bond-Induced Friction at the
      Nanoscale.
AB  - Earthquakes are generally caused by unstable stick-slip motion of faults. This
      stick-slip phenomenon, along with other frictional properties of materials at the
      macroscale, is well-described by empirical rate and state friction (RSF) laws.
      Here we study stick-slip behavior for nanoscale single-asperity silica-silica
      contacts in atomic force microscopy experiments. The stick-slip is quasiperiodic,
      and both the amplitude and spatial period of stick-slip increase with normal load
      and decrease with the loading point (i.e., scanning) velocity. The peak force
      prior to each slip increases with the temporal period logarithmically, and
      decreases with velocity logarithmically, consistent with stick-slip behavior at
      the macroscale. However, unlike macroscale behavior, the minimum force after each
      slip is independent of velocity. The temporal period scales with velocity in a
      nearly power law fashion with an exponent between -1 and -2, similar to
      macroscale behavior. With increasing velocity, stick-slip behavior transitions
      into steady sliding. In the transition regime between stick-slip and smooth
      sliding, some slip events exhibit only partial force drops. The results are
      interpreted in the context of interfacial chemical bond formation and rate
      effects previously identified for nanoscale contacts. These results contribute to
      a physical picture of interfacial chemical bond-induced stick-slip, and further
      establish RSF laws at the nanoscale.

PMID- 29190095
TI  - Mechanism of a Class C Radical S-Adenosyl-l-methionine Thiazole Methyl
      Transferase.
AB  - The past decade has seen the discovery of four different classes of radical S
      adenosylmethionine (rSAM) methyltransferases that methylate unactivated carbon
      centers. Whereas the mechanism of class A is well understood, the molecular
      details of methylation by classes B-D are not. In this study, we present detailed
      mechanistic investigations of the class C rSAM methyltransferase TbtI involved in
      the biosynthesis of the potent thiopeptide antibiotic thiomuracin. TbtI C
      methylates a Cys-derived thiazole during posttranslational maturation. Product
      analysis demonstrates that two SAM molecules are required for methylation and
      that one SAM (SAM1) is converted to 5'-deoxyadenosine and the second SAM (SAM2)
      is converted to S-adenosyl-l-homocysteine (SAH). Isotope labeling studies show
      that a hydrogen is transferred from the methyl group of SAM2 to the 5'
      deoxyadenosine of SAM1 and the other two hydrogens of the methyl group of SAM2
      appear in the methylated product. In addition, a hydrogen appears to be
      transferred from the beta-position of the thiazole to the methyl group in the
      product. We also show that the methyl protons in the product can exchange with
      solvent. A mechanism consistent with these observations is presented that differs
      from other characterized radical SAM methyltransferases.

PMID- 29190098
TI  - Spin-Orbit State-Selective C-I Dissociation Dynamics of the CH3I+ X Electronic
      State Induced by Intense Few-Cycle Laser Fields.
AB  - Studies of ultrafast molecular dynamics induced by intense laser fields can
      reveal new approaches to manipulating chemical reactions in the strong-field
      regime. Here, we show that intense few-cycle laser pulses can induce the spin
      orbit state-selective C-I dissociation of the iodomethane cation (CH3I+) in the X
      electronic state. Irradiation of CH3I by 6 fs laser pulses with peak intensities
      of 1.9 * 1014 W/cm2 followed by femtosecond extreme ultraviolet probing of the
      iodine 4d core-level transitions reveals dissociation of the CH3I+ X 2E1/2 state
      with a time constant of 0.76 +/- 0.16 ps. By contrast, the X 2E3/2 spin-orbit
      ground state does not exhibit any appreciable dissociation on the picosecond time
      scale. The observed spin-orbit state-selective dissociation of the X state is
      rationalized in terms of the laser-induced coupling to the A state. Our results
      suggest that the intense-laser control of photodissociation channels can be
      potentially extended to spin-orbit split states.

PMID- 29190099
TI  - Theoretical Study of the Light-Induced Spin Crossover Mechanism in [Fe(mtz)6]2+
      and [Fe(phen)3]2.
AB  - The deactivation pathway of the light-induced spin crossover process in two
      Fe(II) complexes has been studied by combining density functional theory
      calculations for the geometries and the normal vibrational modes and highly
      correlated wave function methods for the energies and spin-orbit coupling
      effects. For the two systems considered, the mechanism of the photoinduced
      conversion from the low-spin singlet to the high-spin quintet state implies two
      intersystem crossings through intermediate triplet states. However, for the
      [Fe(mtz)6]2+ complex, the process occurs within few picoseconds and involves
      uniquely metal-centered electronic states, whereas for the [Fe(phen)3]2+ system
      the deactivation channel involves both metal to ligand charge transfer and metal
      centered states and takes place in a femtosecond time scale.

PMID- 29190100
TI  - Structure and Dynamics in Formamide-(H2O)3: A Water Pentamer Analogue.
AB  - Water self-association dominates the formation of microsolvated molecular
      clusters which may give rise to complex structures resembling those of pure water
      clusters. We present a rotational study of the complex formamide-(H2O)3 formed in
      a supersonic jet and several monosubstituted isotopologues. Formamide and water
      molecules form a four-body sequential cycle through N-H...O, O-H...O, and O
      H...O?C hydrogen bonds, resulting in a chiral structure with a nonplanar skeleton
      that can be overlapped to that of water pentamer. The analysis of the 14N-nucleus
      quadrupole coupling effects shows the depletion of the electron density of the N
      atom lone pair with respect to the bare formamide that affects the amide group C
      N and C?O distances. The study of the observed tunneling doublets shows that
      formamide-(H2O)3 follows a path to invert its structure driven by the flipping of
      water subunits and passing through successive nonplanar configurations, a motion
      reminiscent of the pseudorotation of water pentamer.

PMID- 29190101
TI  - Accuracy of Td-DFT in the Ultraviolet and Circular Dichroism Spectra of
      Deoxyguanosine and Uridine.
AB  - Accuracy of the time-dependent density functional theory (Td-DFT) was examined
      for the ultraviolet (UV) and circular dichroism (CD) spectra of deoxyguanosine
      (dG) and uridine, using 11 different DFT functionals and two different basis
      sets. The Td-DFT results of the UV and CD spectra were strongly dependent on the
      functionals used. The basis-set dependence was observed only for the CD spectral
      calculations. For the UV spectra, the B3LYP and PBE0 functionals gave relatively
      good results. For the CD spectra, the B3LYP and PBE0 with 6-311G(d,p) basis gave
      relatively permissible result only for dG. The results of other functionals were
      difficult to be used for the studies of the UV and CD spectra, though the
      symmetry adapted cluster-configuration interaction (SAC-CI) method reproduced
      well the experimental spectra of these molecules. To obtain valuable information
      from the theoretical calculations of the UV and CD spectra, the theoretical tool
      must be able to reproduce correctly both of the intensities and peak positions of
      the UV and CD spectra. Then, we can analyze the reasons of the changes of the
      intensity and/or the peak position to clarify the chemistry involved. It is
      difficult to recommend Td-DFT as such tools of science, at least from the
      examinations using dG and uridine.

PMID- 29190103
TI  - Tunneling Reaction Kinetics for the Hydrogen Abstraction Reaction H + H2S -> H2 +
      HS in the Interstellar Medium.
AB  - The hydrogen abstraction reaction between H and H2S, yielding HS and H2 as
      products, has been studied within the framework of interstellar surface
      chemistry. High-temperature rate constants below 2000 K are calculated in the gas
      phase and are in agreement with previously reported values. Subsequently, low
      temperature rate constants down to 55 K are presented for the first time that are
      of interest to astrochemistry, i.e., covering both bimolecular and unimolecular
      reaction mechanisms. For this, a so-called implicit surface model is used. In
      strict terms, this is a structural gas-phase model in which the restriction of
      the rotation in the solid state is taken into account. The calculated kinetic
      isotope effects are explained in terms of the difference in activation and
      delocalization. All rate constants are calculated at the UCCSD(T)-F12/cc-VTZ-F12
      level of theory. Finally, we show that the energetics of the reaction is affected
      to an only small extent by the presence of H2O or H2S molecular clusters that
      simulate an ice surface, calculated at the MPWB1K/def2-TZVP level of theory.

PMID- 29190102
TI  - Integrative Proteomics-Metabolomics Strategy for Pathological Mechanism of
      Vascular Depression Mouse Model.
AB  - Vascular depression (VD), a subtype of depression, is caused by vascular diseases
      or cerebrovascular risk factors. Recently, the proportion of VD patients has
      increased significantly, which severely affects their quality of life. However,
      the current pathogenesis of VD has not yet been fully understood, and the basic
      research is not adequate. In this study, on the basis of the combination of LC-MS
      based proteomics and metabolomics, we aimed to establish a protein metabolism
      regulatory network in a murine VD model to elucidate a more comprehensive impact
      of VD on organisms. We detected 44 metabolites and 304 proteins with different
      levels in the hippocampus samples from VD mice using a combination of metabolomic
      and proteomics analyses with an isobaric tags for relative and absolute
      quantification (iTRAQ) method. We constructed a protein-to-metabolic regulatory
      network by correlating and integrating the differential metabolites and proteins
      using ingenuity pathway analysis. Then we quantitatively validated the levels of
      the bimolecules shown in the bioinformatics analysis using LC-MS/MS and Western
      blotting. Validation results suggested changes in the regulation of
      neuroplasticity, transport of neurotransmitters, neuronal cell proliferation and
      apoptosis, and disorders of amino acids, lipids and energy metabolism. These
      proteins and metabolites involved in these dis-regulated pathways will provide a
      more targeted and credible direction to study the mechanism of VD. Therefore,
      this paper presents an approach and strategy that was applied in integrative
      proteomics and metabolomics for research and screening potential targets and
      biomarkers of VD, which could be more precise and credible in a field lacking
      adequate basic research.

PMID- 29190104
TI  - Excited-State Symmetry Breaking in a Quadrupolar Molecule Visualized in Time and
      Space.
AB  - The influence of the length of the push-pull branches of quadrupolar molecules on
      their excited-state symmetry breaking was investigated using ultrafast time
      resolved IR spectroscopy. For this, the excited-state dynamics of an A-pi-D-pi-A
      molecule was compared with those of an ADA analogue, where the same electron
      donor (D) and acceptor (A) subunits are directly linked without a phenylethynyl
      pi-spacer. The spatial distribution of the excitation was visualized in real time
      by monitoring C=C and C=N vibrational modes localized in the spacer and acceptor
      units, respectively. In nonpolar solvents, the excited state is quadrupolar and
      the excitation is localized on the pi-D-pi center. In medium polarity solvents,
      the excitation spreads over the entire molecule but is no longer symmetric.
      Finally, in the most polar solvents, the excitation localizes on a single D-pi-A
      branch, contrary to the ADA analogue where symmetry breaking is only partial.

PMID- 29190105
TI  - Adaptive Finite Temperature String Method in Collective Variables.
AB  - Here we present a modified version of the on-the-fly string method for the
      localization of the minimum free energy path in a space of arbitrary collective
      variables. In the proposed approach the shape of the biasing potential is
      controlled by only two force constants, defining the width of the potential along
      the string and orthogonal to it. The force constants and the distribution of the
      string nodes are optimized during the simulation, improving the convergence. The
      optimized parameters can be used for umbrella sampling with a path CV along the
      converged string as the reaction coordinate. We test the new method with three
      fundamentally different processes: chloride attack to chloromethane in bulk
      water, alanine dipeptide isomerization, and the enzymatic conversion of
      isochorismate to piruvate. In each case the same set of parameters resulted in a
      rapidly converging simulation and a precise estimation of the potential of mean
      force. Therefore, the default settings can be used for a wide range of processes,
      making the method essentially parameter free and more user-friendly.

PMID- 29190106
TI  - Effect of Aspect Ratio on Multiparticle Auger Recombination in Single-Walled
      Carbon Nanotubes: Time Domain Atomistic Simulation.
AB  - Many-particle Auger-type processes are common in nanoscale materials due to a
      combination of high densities of states that can support multiple excitations and
      substantial Coulomb coupling between charges enhanced by quantum confinement.
      Auger decay dynamics in (10,5) semiconductor carbon nanotubes (CNT) with
      different aspect ratios and particle densities are simulated in time domain using
      global flux surface hopping, recently developed and implemented within Kohn-Sham
      tight-binding density functional theory. Despite an increasing density of states,
      the multiparticle Auger recombination rate decreases in longer CNTs. The
      atomistic simulation shows that the effect is directly related to the coupling
      between electronic states, which decreases as the aspect ratio becomes larger.
      The dependence on tube length is stronger for three-exciton than two-exciton
      recombination and the calculated time scale ratio approaches the experimental
      value measured for long CNTs. Phonon-assisted transitions play a particularly
      important role during Auger recombination. Electron-phonon relaxation is faster
      than the recombination, and Auger transitions are assisted by phonons over a
      range of frequencies up to the G-mode. The involvement of phonons strongly
      enhances the probability of transitions involving asymmetric electron-hole pairs.
      The time-domain atomistic simulation mimics directly time-resolved optical
      experiments and provides a detailed, systematic analysis of the phonon-assisted
      Auger dynamics.

PMID- 29190107
TI  - Minimum Line Width of Surface Plasmon Resonance in Doped ZnO Nanocrystals.
AB  - The optical response of ZnO nanocrystals (NCs) doped with Al (Ga) impurities is
      calculated using a model that incorporates the effects of quantum confinement,
      dielectric mismatch, surface, and ionized impurity scattering. For dopant
      concentrations of a few percent, the NC polarizability is dominated by a
      localized surface plasmon resonance (LSPR) in the infrared (IR) which follows the
      Drude-Lorentz law for NC diameter above ~10 nm but is strongly blue-shifted for
      smaller diameters due to quantum confinement effects. The intrinsic width of the
      LSPR peak is calculated in order to characterize plasmon losses induced by
      ionized impurity scattering. Widths below 80 meV are found in the best cases, in
      agreement with the lowest values recently measured on single NCs. These results
      confirm that doped ZnO NCs are very promising for the development of IR
      plasmonics. The width of the LSPR peak strongly increases when dopants are placed
      near the surface of the NCs or when additional fixed charges are present.

PMID- 29190108
TI  - Palladium-Catalyzed Oxidative Borylation of Allylic C-H Bonds in Alkenes.
AB  - This communication describes an efficient palladium pincer complex-catalyzed
      allylic C-H borylation of alkenes. The transformation exhibits high regio- and
      stereoselectivity with a variety of linear alkenes. A synthetically useful
      feature of this allylic C-H borylation method is that all allyl-Bpin products can
      be isolated in usually high yields. Preliminary mechanistic studies indicate that
      this C-H borylation reaction proceeds via Pd(IV) pincer complex intermediates.

PMID- 29190109
TI  - Correction to Concentration-Driven Fascinating Vesicle-Fibril Transition
      Employing Merocyanine 540 and 1-Octyl-3-methylimidazolium Chloride.

PMID- 29190110
TI  - Ruthenium(II)-Catalyzed Redox-Neutral Oxidative Cyclization of Benzimidates with
      Alkenes with Hydrogen Evolution.
AB  - 1H-Isoindoles and 2H-isoindoles are synthesized via a ruthenium-catalyzed oxidant
      free cyclization of benzimidates with alkenes at room temperature with the
      liberation of H2. Later, 1H-isoindoles were converted into nitrogen-containing
      heterocycles. The proposed reaction mechanism was strongly supported by
      experimental evidence and DFT calculations.

PMID- 29190111
TI  - Iron(III)-Catalyzed Ortho-Preferred Radical Nucleophilic Alkylation of Electron
      Deficient Arenes.
AB  - The untraditional iron-catalyzed, ortho-preferred, radical alkylation of electron
      deficient (hetero)arenes is reported. A variety of electron-deficient arenes were
      shown to react with various primary alkyl sources, producing the alkylated
      (hetero)arenes in good yields. This reaction might be an alkyl radical,
      nucleophilic aromatic substitution reaction, rather than the traditional
      electrophilic Friedel-Crafts reaction. HOMO-LUMO analysis and DFT studies on the
      key transition states underlying the regioselectivity are consistent with the
      observed reactions and the conclusions.

PMID- 29190112
TI  - We Did This, and the Patient Improved: True, True, and Unrelated?

PMID- 29190113
TI  - Organic food and the impact on human health.
AB  - In the last decade, the production and consumption of organic food have increased
      steadily worldwide, despite the lower productivity of organic crops. Indeed, the
      population attributes healthier properties to organic food. Although scientific
      evidence is still scarce, organic agriculture seems to contribute to maintaining
      an optimal health status and decreases the risk of developing chronic diseases.
      This may be due to the higher content of bioactive compounds and lower content of
      unhealthy substances such as cadmium and synthetic fertilizers and pesticides in
      organic foods of plant origin compared to conventional agricultural products.
      Thus, large long-term intervention studies are needed to determine whether an
      organic diet is healthier than a diet including conventionally grown food
      products. This review provides an update of the present knowledge of the impact
      of an organic versus a conventional food diet on health.

PMID- 29190114
TI  - The scientific basis for healthful carbohydrate profile.
AB  - Dietary guidelines indicate that complex carbohydrates should provide around half
      of the calories in a balanced diet, while sugars (i.e., simple carbohydrates)
      should be limited to no more than 5-10% of total energy intake. To achieve this
      public health goal a collective effort from different entities including
      governments, food & beverage industries and consumers is required. Some food
      companies have committed to continually reduce sugars in their products.
      Different solutions can be used to replace sugars in food products but it is
      important to ensure that these solutions are more healthful than the sugars they
      replace. The objectives of this paper are, (1) to identify carbohydrates and
      carbohydrates sources to promote and those to limit for dietary intake and food
      product development, based on current knowledge about the impact of carbohydrates
      on the development of dental caries, obesity and cardio-metabolic disorders (2)
      to evaluate the impact of food processing on the quality of carbohydrates and (3)
      to highlight the challenges of developing healthier products due to the
      limitations and gaps in food regulations, science & technology and consumer
      education.

PMID- 29190115
TI  - Quality of plant-based food materials and its prediction during intermittent
      drying.
AB  - In most drying processes, several physical, chemical and nutritional
      modifications take place in food products. Innovative drying techniques such as
      intermittent drying can enhance the quality of dehydrated products effectively
      and efficiently. Intermittent drying is a technique where drying conditions are
      changed through varying the drying air temperature, humidity, velocity, pressure,
      or even mode of heat input. This drying technique has been successfully applied
      to overcome the problems of conventional drying systems such as longer time
      consumption, case hardening, lower energy efficiency and poor-quality attributes.
      However, as the effect of intermittent drying on food quality is not yet well
      understood, a comprehensive study of quality change during intermittent drying is
      crucial. The main aim of this paper is to present a thorough review of the
      potential effect of intermittent drying methods on physical, chemical,
      nutritional, and stability characteristics of plant-based food material. It is
      found that application of intermittency using different drying systems has a
      significant effect on product quality and its stability. In addition, a
      comprehensive review on existing models of physio/biochemical kinetics for food
      drying is presented. Finally, the paper is concluded with the discussion of the
      current challenges and future directions of intermittent drying for producing
      high-quality dried food products.

PMID- 29190116
TI  - Alarmins in Frozen Shoulder: A Molecular Association Between Inflammation and
      Pain.
AB  - BACKGROUND: The pathophysiological mechanisms behind proliferation of fibroblasts
      and deposition of dense collagen matrix in idiopathic frozen shoulder remain
      unclear. Alarmins (also known as danger signals) are endogenous molecules that
      are released into the extracellular milieu after infection or tissue injury and
      that signal cell and tissue damage. PURPOSE: To investigate whether the presence
      of alarmins is higher in patients with idiopathic frozen shoulder than in control
      subjects. STUDY DESIGN: Controlled laboratory study. METHODS: Shoulder capsule
      samples were collected from 10 patients with idiopathic frozen shoulder and 10
      patients with unstable shoulders (control). The samples were stained with
      hematoxylin and eosin (H&E) and analyzed by immunohistochemistry using antibodies
      against alarmin molecules including high-mobility group protein B1 (HMGB1),
      interleukin 33, S100A8, S100A9, and the peripheral nerve marker PGP9.5.
      Immunoreactivities were rated in a blinded fashion from "none" to "strong."
      Immunohistochemical distribution within the capsule was noted. Before surgery,
      patient-ranked pain frequency, severity, stiffness, and the range of passive
      shoulder motion were recorded and statistically analyzed. RESULTS: Compared with
      control patients, patients with frozen shoulder had greater frequency and
      severity of self-reported pain ( P = .02) and more restricted range of motion in
      all planes ( P < .05). H&E-stained capsular tissue from frozen shoulder showed
      fibroblastic hypercellularity and increased subsynovial vascularity.
      Immunoreactivity of alarmins was significantly stronger in frozen shoulder
      capsules compared with control capsules ( P < .05). Furthermore, the expression
      of the alarmin molecule HMGB1 significantly correlated ( r > 0.9, P < .05) with
      the severity of patient-reported pain. CONCLUSION: This study demonstrates a
      potential role for key molecular danger signals in frozen shoulder and suggests
      an association between the expression of danger molecules and the pain
      experienced by patients.

PMID- 29190117
TI  - Psychobiotics: A new approach for treating mental illness?
AB  - Gut microbiomes may have a significant impact on mood and cognition, which is
      leading experts towards a new frontier in neuroscience. Studies have shown that
      increase in the amount of good bacteria in the gut can curb inflammation and
      cortisol level, reduces symptoms of depression and anxiety, lowers stress
      reactivity, improves memory and even lessens neuroticism and social anxiety. This
      shows that, probably the beneficial gut bacteria or probiotics function
      mechanistically as delivery vehicles for neuroactive compounds. Thus, a
      psychobiotic is a live organism, when ingested in adequate amounts, produces a
      health benefit in patients suffering from psychiatric illness. Study of these
      novel class of probiotics may open up the possibility of rearrangement of
      intestinal microbiota for effective management of various psychiatric disorders.

PMID- 29190118
TI  - Reply: We Did This, and the Patient Improved: True, True, and Unrelated?

PMID- 29190119
TI  - When the Plus Sign is a Negative: Challenging and Reinforcing Embodied Stigmas
      Through Outliers and Counter-Narratives.
AB  - When individuals become aware of their stigma, they attempt to manage their
      identity through discourses that both challenge and reinforce power. Identity
      management is fraught with tensions between the desire to fit normative social
      constructions and counter the same discourse. This essay explores identity
      management in the midst of the embodied stigmas concerning unplanned pregnancy
      during college and raising a biracial son. In doing so, this essay points to the
      difference between outlier narratives and counter-narratives. The author
      encourages health communication scholars to explore conditions under which
      storytelling moves beyond the personal to the political. Emancipatory intent does
      not guarantee emancipatory outcomes. Storytelling can function therapeutically
      for individuals while failing to redress forces that constrain human potential
      and agency.

PMID- 29190121
TI  - Chromosomal Thermal Index: a comprehensive way to integrate the thermal
      adaptation of Drosophila subobscura whole karyotype.
AB  - Drosophila has demonstrated to be an excellent model to study the adaptation of
      organisms to global warming, with inversion chromosomal polymorphism having a key
      role in this adaptation. Here, we introduce a new index (Chromosomal Thermal
      Index or CTI) to quantify the thermal adaptation of a population according to its
      composition of "warm" and "cold" adapted inversions. This index is intuitive, has
      good statistical properties, and can be used to hypothesis on the effect of
      global warming on natural populations. We show the usefulness of CTI using data
      from European populations of D. subobscura, sampled in different years. Out of 15
      comparisons over time, nine showed significant increase of CTI, in accordance
      with global warming expectations. Although large regions of the genome outside
      inversions contain thermal adaptation genes, our results show that the total
      amount of warm or cold inversions in populations seems to be directly involved in
      thermal adaptation, whereas the interactions between the inversions content of
      homologous and non-homologous chromosomes are not relevant.

PMID- 29190120
TI  - Texas Mexican American adult normative studies: Normative data for commonly used
      clinical neuropsychological measures for English- and Spanish-speakers.
AB  - This study aimed to provide normative references for Mexican Americans on
      neuropsychological measures of cognitive functioning. Data were analyzed from a
      total of 797 Mexican-Americans recruited across three Texas-based studies with
      approximately one-half of the participants tested in Spanish. Normative tables
      include: MMSE, AMNART, WMS-III (Logical Memory I, II; Visual Reproduction I, II;
      Digit Span), CERAD, RAVLT, Exit25, CLOX 1 & 2, Trail Making Test- A&B, BNT, COWA,
      and Animal Naming. The norms were stratified by education then age. Normative
      references were generated for Texas-based Mexican Americans and data may be
      limited to the population sampled.

PMID- 29190122
TI  - Translating Biobank Science into Patient-Centered Language.
AB  - INTRODUCTION: This project used Boot Camp Translation (BCT) to translate the
      complex medical jargon of biobanking into locally relevant evidence-based
      messages and materials to support increased knowledge and understanding in the
      local community. METHODS: Biobank BCT was a partnership of 16 community members
      and 5 academic researchers. The partnership met for 8 months. RESULTS: The
      partnership developed five main and seven submessages to assist patients and
      community members in making an informed decision about enrollment in a biobank.
      DISCUSSION: The resulting messages balance an individual's right to privacy and
      choice, while encouraging participation for the greater good.

PMID- 29190123
TI  - Savitzky-Golay smoothing and differentiation for polymerase chain reaction
      quantification.
AB  - In quantitative PCR (qPCR), replicates can minimize the impact of intra-assay
      variation; however, inter-assay variations must be minimized to obtain a robust
      quantification method. The method proposed in this study uses Savitzky-Golay
      smoothing and differentiation (SGSD) to identify a derivative-maximum-based cycle
      of quantification. It does not rely on curve modeling, as is the case with many
      existing techniques. PCR fluorescence data sets challenged for inter-assay
      variations (different thermocycler units, different reagents batches, different
      operators, different standard curves, and different labs) were used for the
      evaluation. The algorithm was compared with a four-parameter logistic model
      (4PLM) method, the Cy0 method, and the threshold method. The SGSD method compared
      favourably with all methods in terms of inter-assay variation. SGSD was
      statistically different from the 4PLM (P = 0.03), Cy0 (P = 0.05), and threshold
      (P = 0.004) methods on relative error comparison basis. For intra-assay
      variations, SGSD outperformed the threshold method (P = 0.005) and equalled the
      4PLM and Cy0 methods (P > 0.05) on relative error basis. Our results demonstrate
      that the SGSD method could potentially be an alternative to sigmoid modeling
      based methods (4PLM and Cy0) when PCR data are challenged for inter-assay
      variations.

PMID- 29190124
TI  - The Role of Media in Non-Directed (Altruistic) Living Kidney Donation.
AB  - This study seeks to characterize how non-directed living kidney donors use media
      and informational resources over the course of their kidney donation journey. We
      conducted semi-structured interviews with non-directed donors (NDDs) who
      initiated kidney transplant chains. Interview transcripts were reviewed and
      references to media or informational resources were classified by type and
      pattern of use. More than half (57%) of NDDs reported that an identifiable media
      or informational resource resulted in their initial interest in donation. Two
      thirds (67%) of NDDs cited the influence of stories and personal narratives on
      their decision to donate. After transplant, media and informational resources
      were used to promote organ donation, connect with other donors or recipients, and
      reflect on donation. From the study's findings, we conclude that media and
      informational resources play an important role in the process of donation for
      NDDs, including inspiring interest in donation through personal narratives. Media
      sources provide emotionally and intellectually compelling discussions that
      motivate potential donors. The results of this study may facilitate the
      development of more targeted outreach to potential donors through use of personal
      narratives in articles and television programming about donation.

PMID- 29190125
TI  - Mitotic instability in triploid and tetraploid one-year-old eastern oyster,
      Crassostrea virginica, assessed by cytogenetic and flow cytometry techniques.
AB  - For commercial oyster aquaculture, triploidy has significant advantages. To
      produce triploids, the principal technology uses diploid * tetraploid crosses.
      The development of tetraploid brood stock for this purpose has been successful,
      but as more is understood about tetraploids, it seems clear that chromosome
      instability is a principal feature in oysters. This paper is a continuation of
      work to investigate chromosome instability in polyploid Crassostrea virginica. We
      established families between tetraploids-apparently stable (non-mosaic) and
      unstable (mosaic)-and normal reference diploids, creating triploid groups, as
      well as tetraploids between mosaic and non-mosaic tetraploids. Chromosome loss
      was about the same for triploid juveniles produced from either mosaic or non
      mosaic tetraploids or from either male or female tetraploids. However, there was
      a statistically significant difference in chromosome loss in tetraploid juveniles
      produced from mosaic versus non-mosaic parents, with mosaics producing more
      unstable progeny. These results confirm that chromosome instability, as
      manifested in mosaic tetraploids, is of little concern for producing triploids,
      but it is clearly problematic for tetraploid breeding. Concordance between the
      results from cytogenetics and flow cytometry was also tested for the first time
      in oysters, by assessing the ploidy of individuals using both techniques. Results
      between the two were non-concordant.

PMID- 29190126
TI  - Understanding the Effects of Stigma Messages: Danger Appraisal and Message
      Judgments.
AB  - Media coverage of health issues has been criticized for creating health stigmas.
      The model of stigma communication (MSC, Smith, 2007) provides insights into why
      this is so, but it has two problems: Some of its mediators have not been
      supported, and it does not do a good job of predicting the transmission of stigma
      messages (i.e., social transmission). We present a revised model of stigma
      message effects in which exposure to stigma messages leads to stigma beliefs and
      stigmatization as a result of a person-oriented danger appraisal. In addition,
      message judgments-shock value and common ground-are introduced as mediators of
      the relationship between danger appraisal and social transmission. Participants
      (N = 200) were randomly assigned to read a health story written either with or
      without the intrinsic features of stigma messages. The revised model of stigma
      message effects was supported: Reading a health news story written with (vs.
      without) the intrinsic features of stigma messages resulted in greater danger
      appraisal, which directly predicted stigma-related outcomes and indirectly
      predicted social transmission through message judgments. Social transmission
      varied by message judgment: Shocking messages were shared in ways that facilitate
      diffusion, but common ground messages were shared with influential others,
      suggesting different means by which stigma as a collective norm may emerge from
      interactions among community members.

PMID- 29190127
TI  - Detection of Salmonella Infection in Chickens by an Indirect Enzyme-Linked
      Immunosorbent Assay Based on Presence of PagC Antibodies in Sera.
AB  - The outcomes of infection of humans and animals with Salmonella range from a
      persistent asymptomatic carrier state to temporal mild gastroenteritis or severe
      systemic infection. A rapid and accurate diagnostic test would help formulate
      strategies for effective prevention of their infections in the animal population.
      Current sequencing data predict that the outer membrane protein, PagC, is present
      in all common Salmonella serovars with sequence similarities of more than 98%.
      PagC sequences in other bacterial species are less than 65% similarity at the
      amino acid level to those of Salmonella PagC. We hypothesized that PagC could be
      immunogenic and detection of antibodies to this protein could be an accurate
      indicator of Salmonella infection. The pagC gene from Salmonella enterica serovar
      Typhimurium CVCC542 was expressed in Escherichia coli. The purified recombinant
      PagC protein was immobilized in microtiter plate wells. Sera from SPF chickens
      infected with Salmonella or other non-Salmonella pathogens by injection were
      added and binding of PagC protein was detected by the horseradish peroxidase
      (HRP)-labeled goat anti-chicken antibody. Sera from Salmonella-infected chickens
      showed high specificity in contrast to the sera from chickens infected with other
      bacteria. When 87 Salmonella antibody-positive sera from Salmonella Pullorum
      orally infected SPF chicken and 93 negative sera from uninfected SPF chicken were
      tested, 98.3% agreement was detected. The rPagC enzyme-linked immunosorbent assay
      (ELISA) and agglutination had 80.6% agreement in detecting 252 clinical chicken
      sera samples. These results suggest that PagC antibody-based indirect ELISA can
      serve as a convenient and novel method for the diagnosis of Salmonella infection.

PMID- 29190128
TI  - Suicide Prevention Media Campaigns: A Systematic Literature Review.
AB  - Suicide prevention media campaigns are gaining traction as a means of combatting
      suicide. The current review set out to synthesize information about the
      effectiveness of these campaigns. We searched four electronic databases for
      studies that provided evidence on the effectiveness of media campaigns. We
      focused on studies that described an evaluation of the effectiveness of an entire
      campaign or a public service announcement explicitly aimed at suicide prevention.
      We identified 20 studies of varying quality. Studies that looked at whether
      campaign exposure leads to improved knowledge and awareness of suicide found
      support for this. Most studies that considered whether campaign materials can
      achieve improvements in attitudes toward suicide also found this to be the case,
      although there were some exceptions. Some studies found that media campaigns
      could boost help-seeking, whereas others suggested that they made no difference
      or only had an impact when particular sources of help or particular types of help
      seeking were considered. Relatively few studies had sufficient statistical power
      to examine whether media campaigns had an impact on the ultimate behavioral
      outcome of suicides, but those that did demonstrated significant reductions. Our
      review indicates that media campaigns should be considered in the suite of
      interventions that might be used to prevent suicide. Evidence for their
      effectiveness is still amassing, but there are strong suggestions that they can
      achieve positive results in terms of certain suicide-related outcomes. Care
      should be taken to ensure that campaign developers get the messaging of campaigns
      right, and further work is needed to determine which messages work and which ones
      do not, and how effective messages should be disseminated. There is an onus on
      those developing and delivering campaigns to evaluate them carefully and to share
      the findings with others. There is a need for evaluations that employ rigorous
      designs assessing the most pertinent outcomes. These evaluations should explore
      the nature of given campaigns in detail - in particular the messaging contained
      within them - in order to tease out which messages work well and which do not.
      They should also take into account the reach of the campaign, in order to
      determine whether it would be reasonable to expect that they might have their
      desired effect.

PMID- 29190129
TI  - Polymorphism rs10483727 in the SIX1/SIX6 Gene Locus Is a Risk Factor for Primary
      Open Angle Glaucoma in a Saudi Cohort.
AB  - AIMS: Variant rs10483727 in the SIX1/SIX6 locus has been significantly associated
      with primary open angle glaucoma (POAG) in multiple ethnic groups. We conducted a
      case-control study to investigate the association between this variant and POAG
      in a Saudi cohort. MATERIALS AND METHODS: Polymorphism rs10483727 was genotyped
      by using a TaqMan(r) assay in 186 subjects comprising 92 unrelated POAG cases and
      94 controls all of Saudi origin. RESULTS: The "C" allele frequency was 0.33 and
      0.45 among POAG cases and controls, respectively (odds ratio [OR] = 0.58, 95%
      confidence interval [CI] = 0.38-0.89; p = 0.013), suggesting a protective effect;
      and the "T" allele was associated with increased susceptibility to POAG (OR =
      1.7, 95% CI = 1.11-2.58; p = 0.013). Genotype distribution was also significantly
      associated with POAG (chi2 = 6.41, df = 2, p = 0.041). Endophenotype traits such
      as intraocular pressure and cup/disk ratio did not show any significant genotype
      distribution in POAG cases. A binary logistic regression analysis used to
      evaluate the effects of age, gender, and genotype on the likelihood of having
      POAG showed that genotype distribution (p = 0.012) significantly affected the
      disease outcome as compared with age (p = 0.055) and sex (p = 0.432). CONCLUSION:
      The "T" allele of the rs10483727 polymorphism is an independent significant risk
      factor for POAG in the Saudi population.

PMID- 29190130
TI  - Genomic relationships among sixteen species of Avena based on (ACT)6
      trinucleotide repeat FISH.
AB  - Knowledge of the locations of repeat elements could be very important in the
      assembly of genome sequences and their assignment to physical chromosomes.
      Genomic and species relationships among 16 species were investigated using
      fluorescence in situ hybridization (FISH) with the Am1 and (ACT)6 probes. The Am1
      oligonucleotide probe was particularly enriched in the C genomes, whereas the
      (ACT)6 trinucleotide repeat probe showed a diverse distribution of hybridization
      patterns in the A, AB, C, AC, and ACD genomes but might not be present in the B
      and D genomes. The hybridization pattern of Avena sativa was very similar to that
      of A. insularis, indicating that this species most likely originated from A.
      insularis as a tetraploid ancestor. Although the two FISH probes failed to
      identify relationships of more species, this proof-of-concept approach opens the
      way to the use of FISH probes in assigning other signature elements from genomic
      sequence to physical chromosomes.

PMID- 29190132
TI  - CORRECTION.

PMID- 29190131
TI  - A comparison of overtime patrol stops made inside and out of cluster identified
      hotspots.
AB  - OBJECTIVE: The annual rate of impaired driving crashes in the United States has
      remained nearly constant over the last decade. While engineers, educators,
      enforcement, and emergency response personnel have worked diligently in their
      combined efforts to reduce the loss of life, there is still significant progress
      to be made. One area of recent interest is the use of data driven enforcement.
      The basis for data driven enforcement is the use of statistical clustering to
      identify geographic areas that represent the location of problem identification
      for various criminal or traffic offenses. In the case of impaired driving
      fatalities, the clustering represents locations with high rates of impaired
      driving crashes. Law enforcement officers and supervisors may allocate resources
      towards more specifically and efficiently addressing problem areas. METHODS:
      While data driven enforcement has been proven to be an effective tool in
      addressing crime and traffic safety problems, it has been a slow process for
      agencies to adopt data driven techniques. This study aims to explore the
      difference in traffic stops made inside and outside of hotspot identified areas.
      The study uses data from the Stark County Operating a Vehicle Impaired Task Force
      between 2013 and 2014. RESULTS: The analysis determined that stop occurring in
      hotspot defined areas are more likely to result in impaired driving arrests and
      seatbelt citations. Additionally it is found that the average cost of impaired
      driving arrests is significantly cheaper for stops occurring inside of hotspot
      areas. CONCLUSION: Clustering as a means of directing law enforcement efforts are
      a way to increase the productivity and benefits of law enforcement agencies with
      limited finances or personnel. From this study it is seen that traffic stops made
      within defined cluster or hot spot areas are more effective in resulting in OVI
      arrests.

PMID- 29190133
TI  - BUILDING A BRIDGE IN LONDON, FOR MY CAREER AND MY ADOLESCENT PITUITARY PATIENTS.

PMID- 29190134
TI  - AUTHOR'S REPLY.

PMID- 29190135
TI  - AACE/ACE POSITION STATEMENT ON THE USE OF FOLLOW-ON BIOLOGICS AND BIOSIMILARS FOR
      ENDOCRINE DISEASES.
AB  - : This document represents the official position of the American Association of
      Clinical Endocrinologists and American College of Endocrinology. Where there were
      no randomized controlled trials or specific U.S. FDA labeling for issues in
      clinical practice, the participating clinical experts utilized their judgment and
      experience. Every effort was made to achieve consensus among the committee
      members. Position and consensus statements are meant to provide guidance, but
      they are not to be considered prescriptive for any individual patient and cannot
      replace the judgment of a clinician. ABBREVIATIONS: BPCIA = Biologics Price
      Competition and Innovation Act; FDA = Food and Drug Administration; FFDC =
      Federal Food Drug and Cosmetics Act; PHS = Public Health Services Act; TE =
      therapeutic equivalence.

PMID- 29190136
TI  - NUTRITIONAL INSULIN OR GLP-1 RECEPTOR AGONIST: CROSSROADS IN THE TREATMENT OF
      TYPE 2 DIABETES MELLITUS.

PMID- 29190137
TI  - HIGH-RISK GASTRIC PATHOLOGY AND PREVALENT AUTOIMMUNE DISEASES IN PATIENTS WITH
      PERNICIOUS ANEMIA.
AB  - OBJECTIVE: Pernicious anemia (PA) develops from atrophic gastritis due to
      autoimmune destruction of parietal cells and results in achlorhydria, vitamin B12
      and iron deficiencies, anemia, neurologic deficits, and premalignant and
      malignant stomach lesions. We report the presentation, diagnosis and gastric
      complications of PA in patients from an endocrinology practice. METHODS: Thirty
      four patients (31 female, 3 male) with PA who underwent
      esophagogastroduodenoscopy (EGD) or gastrectomy were identified. Pertinent
      clinical, laboratory, and pathology findings were reviewed and summarized.
      RESULTS: The mean age of patients was 58.6 +/- 14.2 years; the onset of PA was
      age 50.2 +/- 15.3 years. Anemia reflected vitamin B12 and/or iron deficiencies.
      Parietal cell antibodies (PCA) were detected in 97% of patients, and intrinsic
      factor blocking antibody (IFBA) was found in 52%. Fasting gastrin and
      chromogranin A levels were elevated (1,518.0 +/- 1,588.3 pg/mL, and 504.9.1 +/-
      1,524.9 ng/mL respectively). Autoimmune or immunologic diseases (AIDs) were
      present in 32/34 patients. Stomach pathology showed premalignant or malignant
      lesions in 26 patients, including gastric neuroendocrine tumors (GNETs) in 6 and
      adenocarcinoma in 1. One patient presented with neurologic symptoms and subacute
      combined degeneration of the posterior column of the spinal cord. CONCLUSION: PA
      should be suspected in patients with unexplained anemia or neurologic symptoms.
      The diagnosis of PA relies on fasting gastrin and gastric auto-antibody testing,
      in addition to hematologic evaluation. EGD with measurement of gastric pH and
      biopsies of the fundus and antrum identifies patients with achlorhydria, atrophic
      gastritis, and premalignant and malignant stomach lesions. EGD surveillance of
      patients with high-risk stomach lesions is recommended. ABBREVIATIONS: AID =
      autoimmune or immunologic disease; EGD = esophagogastroduodenoscopy; GNET =
      gastric neuroendocrine tumor; IFBA = intrinsic factor blocking antibody; PA =
      pernicious anemia; PCA = parietal cell antibody; T1D = type 1 diabetes.

PMID- 29190138
TI  - LETTER TO THE EDITOR.

PMID- 29190139
TI  - The 50/50 Block Schedule: Impact on Residents' and Preceptors' Perceptions,
      Patient Outcomes, and Continuity of Care.
AB  - PROBLEM: Traditionally, internal medicine continuity clinic consists of a half
      day per week, regardless of rotation, which may create conflict with ongoing
      inpatient responsibilities. A 50/50 block schedule, which alternates inpatient
      and outpatient rotations and concentrates continuity clinic during outpatient
      rotations, minimizes conflicting responsibilities. However, its impact on patient
      care has not been widely studied. Continuity is a concern, and intervisit
      continuity in particular has not been evaluated. INTERVENTION: We implemented a
      50/50 block model with "clinic buddy" system to optimize continuity and assessed
      outcomes pre- and postintervention. Residents alternated inpatient and elective
      blocks, with clinic 1 full day per week on elective blocks only. Resident and
      preceptor perceptions were measured using 5-point Likert surveys to evaluate
      impact on clinic experience and workload. The authors calculated visit and
      intervisit continuity using a Usual Provider of Care index and measured blood
      pressure and hemoglobin A1c as quality markers to evaluate the impact on
      continuity and quality of care. CONTEXT: Participants were 208 medicine residents
      and 39 core faculty members at 3 University of Pittsburgh Medical Center clinics.
      The intervention was implemented in June 2014. OUTCOME: In the 50/50 system,
      inpatient distractions decreased (3.59 vs. 1.71, p < .001). Residents more
      strongly agreed that there was adequate time for conferences (3.33 vs. 4.05),
      they worked well within the system to achieve best patient care (3.13 vs. 3.61),
      and multidisciplinary teams worked well together (3.51 vs. 4.08) (all p < .001).
      Intervisit continuity was unchanged (73%, both models, p = .79). Visit continuity
      decreased (67.2% vs. 63.7%, p < .001). Blood pressure and hemoglobin A1c were
      unchanged. LESSONS LEARNED: This 50/50 model minimized inpatient distractions in
      clinic and increased perceived time for learning. Residents reported improved
      sense of patient ownership, relations within the multidisciplinary team, and
      integration into the clinic system. Intervisit continuity was preserved, visit
      continuity was slightly decreased, and patient outcomes were not impacted in this
      model.

PMID- 29190140
TI  - Validity Evidence for a Residency Admissions Standardized Assessment Letter for
      Pediatrics.
AB  - : Construct: This study aims to provide validity evidence for the standardized
      Assessment Letter for Pediatrics as a measure of competencies expected of a 1st
      year pediatrics resident as part of a pediatric residency admissions process.
      BACKGROUND: The Narrative Letter of Recommendation is a frequently used tool in
      the residency admissions process even though it has poor interrater reliability,
      lacks pertinent content, and does not correlate with residency performance. A
      newer tool, the Standardized Letter, has shown validity evidence for content and
      interrater reliability in other specialties. We sought to develop and provide
      validity evidence for the standardized Assessment Letter for Pediatrics.
      APPROACH: All 2012 and 2013 applicants invited to interview at the University of
      Geneva Pediatrics Residency Program provided 2 standardized Assessment Letters.
      Content for the letter was based on CanMEDS roles and ratings of 6 desired
      competencies and an overall assessment. Validity evidence was gathered for
      internal structure (Cronbach's alpha and generalizability), response process
      (interrater reliability with intraclass correlation), relations to other
      variables (Pearson's correlation coefficient), and consequences (logistic
      regression to predict admission). RESULTS: One hundred fourteen faculty completed
      142 standardized Assessment Letters for 71 applicants. Average overall assessment
      was 3.0 of 4 (SD = 0.59). Cronbach's alpha was 0.93. The G-coefficient was 0.59.
      The decision study projected that four Assessment Letters are needed to attain a
      G-coefficient of 0.73. Applicant variance (28.5%) indicated high applicant
      differentiation. The Assessment Letter intraclass coefficient was 0.51, 95%
      confidence interval (CI) [0.43, 0.59]. Assessment Letter scores were correlated
      with the structured interview (r = .28), 95% CI [0.05, 0.51]; global rating (r =
      .36), 95% CI [0.13, 0.58]; and admissions decision (r = .25), 95% CI [0.02,
      0.46]. Assessment Letter scores did not predict the admissions decision (odds
      ratio = 1.67, p = .37) after controlling for the unique contribution of the
      structured interview and global rating scores. CONCLUSION: Validity evidence
      supports use of the Assessment Letter for Pediatrics; future studies should
      refine items to improve predictive validity and explore how to best integrate the
      Assessment Letter into the residency admissions process.

PMID- 29190141
TI  - Childhood Maltreatment, Bullying Victimization, and Psychological Distress Among
      Gay and Bisexual Men.
AB  - Sexual minority men report higher psychological distress than heterosexual men,
      including depression and anxiety. Research suggests that these health disparities
      may be due to the heightened stressors that gay, lesbian, and bisexual
      individuals experience. Some of these stressors occur early on in life, such as
      childhood abuse and bullying, and may include stressors that are topically
      related to sexual minority status, such as anti-gay bullying and teasing for
      gender nonconformity to masculine gender norms. We tested a structural equation
      model on the association between negative childhood experiences and adult
      psychological distress among 304 gay and bisexual men. The model fit the data
      well, and demonstrated an indirect effect of negative childhood experiences on
      adult psychological distress via dysfunctional thoughts toward oneself. The
      results integrate the childhood abuse and anti-gay bullying victimization
      literatures by showing that both forms of adverse childhood experiences are
      associated with adult psychological distress. The findings suggest the benefit of
      treatments to reduce negative, dysfunctional thoughts among gay and bisexual men
      who have experienced adverse childhood events.

PMID- 29190142
TI  - Biomedical Science Undergraduate Major: A New Pathway to Advance Research and the
      Health Professions.
AB  - PROBLEM: Many students entering professional degree programs, particularly M.D.,
      Ph.D., and M.D./Ph.D., are not well prepared regarding the breadth of scientific
      knowledge required, communication skills, research experience, reading and
      understanding the scientific literature, and significant shadowing (for M.D.
      related professions). In addition, physician scientists are a needed and
      necessary part of the academic research environment but are dwindling in numbers.
      INTERVENTION: In response to predictions of critical shortages of clinician
      investigators and the lack of proper preparation as undergraduates for these
      professions, the Biomedical Science (BMS) undergraduate major was created at The
      Ohio State University to attract incoming college freshmen with interests in
      scientific research and the healthcare professions. The intent of this major was
      to graduate an elite cohort of highly talented individuals who would pursue
      careers in the healthcare professions, biomedical research, or both. CONTEXT:
      Students were admitted to the BMS major through an application and interview
      process. Admitted cohorts were small, comprising 22 to 26 students, and received
      a high degree of individualized professional academic advising and mentoring. The
      curriculum included a minimum of 4 semesters (or 2 years) of supervised research
      experience designed to enable students to gain skills in clinical and basic
      science investigation. In addition to covering the prerequisites for medicine and
      advanced degrees in health professions, the integrated BMS coursework emphasized
      research literacy as well as skills related to work as a healthcare professional,
      with additional emphasis on independent learning, teamwork to solve complex
      problems, and both oral and written communication skills. Supported by Ohio
      State's Department of Internal Medicine, a unique clinical internship provided
      selected students with insights into potential careers as physician scientists.
      OUTCOME: In this educational case report, we describe the BMS undergraduate major
      and its outcomes after 10 years of implementation. Major outcomes include the
      strength of the major's matriculates (average ACT score = 32.6; average high
      school class percentile rank = 95.5) and the high percentage of BMS students who
      pursued graduate/professional degrees (91%; n = 110). Other markers of success
      include the strong focus on research, which resulted in 120 articles published by
      graduates to date (range = 0-12/student; 43% with at least 1 peer-reviewed
      journal article). LESSONS LEARNED: Based on its successes, adoption of a similar
      program at other academic medical centers would help feed the pipeline of well
      trained health professionals and biomedical researchers.

PMID- 29190143
TI  - Perceptions of Tobacco Control Media Campaigns Among Smokers With Lower
      Socioeconomic Status.
AB  - People with low socioeconomic status (SES) in the United States have disparately
      high rates of smoking and experience disproportionately high burdens of smoking
      related disease. Tobacco control media campaigns are a critical strategy for
      reducing tobacco use prevalence, but evidence is mixed about the optimal use of
      mass media to reach and promote tobacco use cessation among people with low SES.
      Improved understanding of the factors influencing how low-SES tobacco users
      evaluate tobacco control media campaigns may inform development of more effective
      messages and strategies. Focus groups with primarily low-SES smokers in
      Connecticut were conducted, finding that participants had seen many tobacco
      control television ads that used graphic imagery and testimonials, but
      participants voiced two main themes that limited ad effectiveness: (1) skepticism
      about the content of ads, the role of the tobacco industry and the government in
      sponsoring the ads, and the safety and efficacy of cessation supports; and (2)
      barriers to quitting such as stress, social contexts, and addiction that
      participants perceived as being underappreciated in the context of the ads.
      Tobacco control media campaigns targeting low-SES tobacco users may need
      additional messages, tools, or refinements to more optimally motivate this group
      to make quit attempts.

PMID- 29190144
TI  - Heterogeneity in Gender/Sex Sexualities: An Exploration of Gendered Physical and
      Psychological Traits in Attractions to Women and Men.
AB  - Sexuality research has generally privileged attractions based on partners' sexed
      physical bodies over attractions based on other features, including gender
      expression and personality traits. Gender may actually be quite central to sexual
      attractions. However, its role has received little empirical attention. To
      explore how gendered and sexed features, among others, are related to sexual
      attractions, the current study assessed how sexually diverse individuals
      described their attractions to feminine, masculine, and gender-nonspecific
      features of women and men. A sample of 280 individuals responded to the open
      ended questions: "What do you find attractive in a man?" and "What do you find
      attractive in a woman?" We coded responses as pertaining to physical and/or
      psychological features, and as being gendered masculine, feminine, or gender
      nonspecific. Our analyses showed that participants named gender-nonspecific
      features most frequently in responses to both questions, feminine features more
      than masculine features in attractions to women, and masculine features more than
      feminine features in attractions to men. Additionally, participants named
      feminine physical features more than masculine physical features, and masculine
      psychological features more than feminine psychological features, both in their
      attractions to women and overall. These results highlight the importance of
      considering attractions based on gender, rather than sex alone.

PMID- 29190145
TI  - The principles and practice of narrative medicine, edited by Rita Charon,
      Sayantani DasGupta, Nellie Hermann, Craig Irvine, Eric Marcus, Edgar Rivera
      Colon, Danielle Spencer, and Maura Spiegel.

PMID- 29190146
TI  - Prevalence of depression after TBI in a prospective cohort: The SHEFBIT study.
AB  - OBJECTIVE: The objective is to measure the prevalence of depression after
      traumatic brain injury (TBI) and the features associated with increased risk in a
      cohort that reflects clinical practice. METHODS: Prospective TBI admissions to a
      large Teaching Hospital Emergency Department were recruited over a 2-year period.
      Assessments for depression and other psychosocial and global outcomes were
      completed at 3 months post-injury. Comparisons were made with demographic and
      injury features of interest to establish any associations of depression risk.
      RESULTS: Out of 827 individuals, 774 (94%) successfully attended follow-up. A
      percentage of 56.3 had depression using a HADS-D >8. Depressed individuals had
      higher levels of post-concussion symptoms and worse psychosocial and global
      outcome ratings. In multivariable analysis, features associated with depression
      were TBI severity, previous psychiatric history, alcohol intoxication at time of
      injury, female gender and nonwhite ethnicity. Those with a normal CT scan showed
      higher risk than those with only mild abnormality and were comparable to those
      with much more marked CT changes. CONCLUSION: The 3-month prevalence of
      depression after TBI is very high and associated with several injury and
      demographic features. Future long-term follow-up of this cohort aims to confirm
      the features that increase risk; this may allow the earlier targeting of
      susceptible individuals for depression interventions.

PMID- 29190147
TI  - When normal scores don't equate to independence: Recalibrating ratings of
      neurobehavioural disability from the 'St Andrew's - Swansea Neurobehavioural
      Outcome Scale' to reflect context-dependent support.
AB  - PRIMARY OBJECTIVE: Context is critical to the interpretation of measurement
      instruments that capture acquired brain injury (ABI) outcomes. Ratings reflect
      behaviours and abilities observed in a particular setting; it cannot be assumed
      that results are generalizable beyond these. This study explored the utility of a
      method to convey the impact of context-dependent support given on ratings of
      neurobehavioural disability (NBD) using the St Andrews-Swansea Neurobehavioural
      Outcome Scale (SASNOS). METHODS AND PROCEDURES: A supplementary SASNOS scoring
      system was developed using a mixed-methods approach. Dependency ratings were used
      to recalibrate standardised SASNOS scores to reflect support received. To aid
      interpretation, an expert panel reviewed SASNOS ratings for 50 ABI cases
      participating in residential neurobehavioural rehabilitation programmes. An end
      user survey was undertaken to explore some of its psychometric properties.
      Finally, a representative case study was employed to illustrate its clinical
      utility. MAIN OUTCOMES: The expert panel identified three dependency profiles:
      (1) Normal/Independent; (2) Normal/Dependent; and (3) Abnormal/Review. Survey
      results supported face and construct validity of the supplementary system; the
      case study demonstrated benefits of discriminating between dependency profiles.
      CONCLUSIONS: The supplementary scoring system enables SASNOS to convey the impact
      of support received on ratings of NBD, solidifying its usefulness for measuring
      outcomes in rehabilitation.

PMID- 29190148
TI  - Sexual Inactivity among Transfeminine Persons: A Canadian Respondent-Driven
      Sampling Survey.
AB  - Sexual health research with transfeminine persons (individuals assigned male at
      birth who identify as female or feminine) has focused on HIV infection and sexual
      function following medical treatments. Yet, approximately half of transfeminine
      persons in Ontario, Canada, reported no partnered sex in the previous year.
      Therefore, we identified sociodemographic, social, and psychosocial factors
      associated with past-year sexual inactivity among transfeminine Ontarians. A
      multi-mode respondent-driven sampling survey of transgender people was conducted
      in 2009-2010 (N = 433), including 173 transfeminine individuals who had ever been
      sexually active. Frequencies and regression models were weighted using RDS II
      methods; prevalence ratios were estimated from logistic regression models using
      average marginal predictions. Of sexually experienced transfeminine persons, 43%
      (95% CI [31, 55]) reported no past-year sex partners. Sexual inactivity was
      independently associated with older age, childhood sexual abuse, and residing
      outside of the province's largest city. Transfeminine persons who had genital
      surgery for gender affirmation were less likely to be abstinent, as compared to
      those who were living in their felt gender without surgery. Transphobic
      harassment and higher levels of trans-related sexual body image worries were also
      associated with sexual inactivity, as was reduced sexual satisfaction.
      Implications for research and clinical practice are discussed.

PMID- 29190150
TI  - Intravenous saline administration in patients with severe acquired brain injury
      and orthostatic intolerance for tilt-table mobilization.
AB  - PRIMARY OBJECTIVE: This study aimed to investigate the effect of intravenous
      saline administration on orthostatic hypotension (OH) during head up tilt (HUT)
      and the change in the renin-angiotensin-aldosterone system before and after HUT
      in patients with severe acquired brain injury (ABI). RESEARCH DESIGN: The study
      is designed as an observational study. METHODS AND PROCEDURES: Fourteen patients
      with ABI, low level of consciousness and OH were monitored before, during and
      after HUT with non-invasive beat-to-beat blood pressure measurement, and
      transcranial Doppler determination of middle cerebral artery blood flow velocity.
      Blood samples were collected before and after two HUT sessions separated by 1
      hour and saline was administered in between. MAIN OUTCOMES AND RESULTS: Patients'
      ability to stand upright did not change after saline administration due to OH.
      The patients showed signs of reduced cerebral autoregulation at both HUT
      sessions. The patients had a significant lower level of renin and angiotensin II
      but not aldosterone. CONCLUSIONS: Patients with severe ABI and OH demonstrate no
      improvement in standing time with reduced plasma renin and angiotensin II after
      two HUT sessions and 1 hour fluid administration. Research focusing on the
      ability to retain fluid after bed rest is warranted.

PMID- 29190149
TI  - Teacher Perspectives of Interdisciplinary Coteaching Relationships in a Clinical
      Skills Course: A Relational Coordination Theory Analysis.
AB  - : Phenomenon: Interdisciplinary coteaching has become a popular pedagogic model
      in medical education, yet there is insufficient research to guide effective
      practices in this context. Coteaching relationships are not always effective,
      which has the potential to affect the student experience. The purpose of this
      study was to explore interdisciplinary coteaching relationships between a
      physician (MD) and social behavioral scientist (SBS) in an undergraduate clinical
      skills course. We aimed to gain an in-depth understanding of what teachers
      perceive as influencing the quality of relationships to begin to construct a
      framework for collaborative teaching in medical education. APPROACH: A
      qualitative study was conducted consisting of 12 semistructured interviews (6 MD
      and 6 SBS) and 2 monodisciplinary focus groups. Sampling was purposive and aimed
      at maximal variation from among 64 possible faculty. The data were analyzed using
      the constant comparative method to develop a grounded theory. FINDINGS: Five
      major themes resulted from the analysis that outline a framework for
      interdisciplinary coteaching: respect, shared goals, shared knowledge and
      understanding, communication, and complementary pairings. Insights: The first 4
      themes align with elements of relational coordination theory, an organizational
      theory of collaborative practice that describes how work roles interact. The
      complementary pairings extend this theory from work roles to individuals, with
      unique identities and personal beliefs and values about teaching. Prior studies
      on coteaching have not provided a clear linkage to theory. The conceptual
      framework helps suggest future directions for coteaching research and has
      practical implications for administrative practices and faculty development.
      These findings contribute to the sparse research in medical education on
      interdisciplinary coteaching relationships.

PMID- 29190151
TI  - The effect of repeated light-dark shifts on uterine receptivity and early
      gestation in mice undergoing embryo transfer.
AB  - Female shift workers are at increased risk for negative reproductive outcomes,
      and animal evidence suggests that manipulation of the light-dark cycle is
      detrimental to early gestation in female mice. Specifically, failure of
      implantation may be responsible for these findings. The objective of this study
      was to better delineate which reproductive processes are vulnerable to
      detrimental effects of maternal circadian disturbance. We exposed mice undergoing
      embryo transfer to repetitive phase advances of the photoperiod. Embryos were
      derived from donor sperm and eggs from mice living in normal light-dark
      conditions to isolate the effects of photoperiod disruption on uterine
      receptivity and early gestation. Twenty-eight mice receiving embryo transfer
      underwent an experimental light-dark condition (advance of lights on and lights
      off by 6 hours every 4 days). Twenty-eight mice remained in a normal light-dark
      condition. Animals lived in their assigned light-dark condition beginning 2 weeks
      prior to embryo transfer and ending the day of uterine necropsy (post-coitus day
      14.5). Wilcoxon-Mann-Whitney test demonstrated no significant differences between
      control and experimental light-dark conditions in pups (Z=0.10, p=.92),
      resorptions (Z=0.20, p=.84), or implantations (Z=-0.34, p=.73). Pup and placental
      weights were similar between groups. In this investigation, uterine receptivity
      and maintenance of early gestation were preserved despite recurrent phase
      advances in photoperiod. This finding, in the context of the current literature,
      suggests that the negative effects of circadian disruption are mediated by
      reproductive processes upstream of implantation.

PMID- 29190152
TI  - Attribution Patterns in Women With and Without Orgasmic Difficulties.
AB  - People with sexual problems are more likely to attribute negative sexual
      experiences to themselves, in contrast with sexually functional individuals who
      attribute negative sexual experiences to external factors such as the
      circumstance or situation. We investigated attribution patterns in women
      reporting difficult or absent orgasm-a group only minimally investigated in this
      regard-to determine whether they differed from women without orgasmic problems.
      Using an internet-based approach, we compared attribution responses of 376 women
      with orgasmic difficulty with 367 women without orgasmic difficulty to five
      sexual scenarios, two presenting positive sexual experiences and three presenting
      negative sexual experiences. Women with orgasmic difficulty were more likely to
      take blame for any negative sexual experience, including ones not related to
      orgasmic difficulty. They were also more likely to attribute responsibility to
      their partner's lack of skill, whereas orgasmic women attributed negative
      outcomes more to circumstance. Women with orgasmic difficulty were also less
      likely to assume credit or responsibility for positive sexual experiences.
      Differences between orgasmic and non-orgasmic groups persisted or were augmented
      when age and arousal difficulty were controlled. These results emphasize the
      stark contrast in the way women with and without orgasmic problems approach
      sexual situations and suggest several therapeutic strategies.

PMID- 29190153
TI  - Cognitive function and participation in children and youth with mild traumatic
      brain injury two years after injury.
AB  - BACKGROUND: 10-20% of children and youth with mild traumatic brain injury (mTBI)
      suffer from long-term cognitive impairments with, supposedly, a negative impact
      on most domains of functioning. OBJECTIVES: To describe cognitive functioning and
      participation in children and youth two-years post-mTBI and to determine
      associated risk factors. METHODS: Cross-sectional study among 73 patients (aged 6
      22 years), hospital diagnosed with mTBI. Linear regression modelling was used to
      investigate the effect of potential predictors on cognitive functioning as
      measured with a neuropsychological assessment (NPA), two-years post-injury.
      Extent of participation was assessed using the Child and Adolescent Scale of
      Participation and correlation analysis was conducted to examine its association
      with level of cognitive functioning. RESULTS: 7-15% of all participants had
      impaired cognitive functions, especially in the domains of processing speed,
      inhibitory control, cognitive flexibility, visuospatial constructional ability
      and visuospatial memory. Lower level of education and pre-injury cognitive
      problems were predictive for a lower level of long-term cognitive functioning.
      Slower inhibition speed, impaired visuospatial and verbal working memory were
      associated with reduced participation. DISCUSSION AND CONCLUSIONS: Persisting
      cognitive problems two years after mTBI were mostly related to the lower level of
      education and to pre-injury cognitive problems. Although participation of the
      patients was reported by parents to be relatively high, slower inhibition speed,
      impaired visuospatial and verbal working memory were associated with reduced
      participation.

PMID- 29190154
TI  - In vitro anti-inflammatory activity of spherical silver nanoparticles and
      monodisperse hexagonal gold nanoparticles by fruit extract of Prunus serrulata: a
      green synthetic approach.
AB  - Recently, green metal nanoparticles have received global attention owing to their
      economical synthesis, biocompatible nature, widespread biomedical and
      environmental applications. Current study demonstrates a sustainable approach for
      the green synthesis of silver nanoparticles (P-AgNPs) and gold nanoparticles (P
      AuNPs) from P. serrulata fresh fruit extract. The silver and gold nanoparticles
      were synthesized in a very rapid, efficient and facile manner, within 50 min and
      30 s at 80  degrees C, respectively. The nanoparticles were characterized by
      using visual observation, UV-Vis, FE-TEM, EDX, elemental mapping, FT-IR, XRD and
      DLS, which confirmed the formation of monodispersed, crystalline and stable
      nanoparticles. Further, we explored these nanoparticles for anti-inflammatory
      activity through inhibition of downstream NF-kappaB activation in macrophages
      (RAW264.7). We demonstrated that the nanoparticles reduced expression of
      inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PEG2),
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was
      attenuated in lipopolysaccharide (LPS)-induced RAW264.7 cells. Furthermore,
      nanoparticles significantly suppressed LPS-induced activation of NF-kappaB
      signalling pathway via p38 MAPK in RAW 264.7 cells. To the best of our knowledge,
      this is the first report on the efficient green synthesis of P-AgNPs and P-AuNPs
      using P. serrulata fresh fruit extract and its in vitro anti-inflammatory
      effects. Collectively, our results suggest that P. serrulata fresh fruit extract
      is a green resource for the eco-friendly synthesis of P-AgNPs and P-AuNPs, which
      further can be utilized as a novel therapeutic agent for prevention and cure of
      inflammation due to their biocompatible nature.

PMID- 29190155
TI  - Purified Dry Paullinia cupana (PC-18) Extract for Chemotherapy-Induced Fatigue:
      Results of Two Double-Blind Randomized Clinical Trials.
AB  - Fatigue is frequent among oncologic patients. Unpurified Paullinia cupana dry
      extract showed encouraging results for chemotherapy-induced fatigue in our
      previous studies. We report two randomized, double-blind studies with a
      standardized dry purified Paullinia cupana extract named PC-18. For both studies,
      we recruited early breast cancer patients who had an increase in their fatigue
      scores after their first cycle of adjuvant chemotherapy. In the first study, we
      compared an oral dose of 37.5 mg of PC-18 twice daily with placebo. In the second
      study, we examined PC-18 at either 7.5 or 12.5 mg orally twice daily versus
      placebo. In both studies, PC-18 was not superior to placebo as assessed by both
      Chalder and Brief Fatigue Inventory (BFI) fatigue questionnaires, probably
      reflecting unexpectedly good placebo antifatigue activity. Since all capsules
      employed in both studies contained about 100 mg of magnesium silicate as an
      excipient, we retrospectively evaluated frozen serum samples from the second
      study and found a significant increase in magnesium levels after patients
      received placebo. By multivariate analysis, higher prerandomization magnesium
      levels and higher BFI scores together with the use of a 12.5 mg dose of PC-18 all
      correlated significantly with higher posttreatment BFI scores. We observed no
      significant toxicities in any of the trials. We conclude that the absence of
      differences between PC-18 and placebo may be due to the unexpectedly high
      antifatigue activity of the placebo in these studies. Further studies evaluating
      the role of magnesium supplementation for chemotherapy-induced fatigue are
      needed.

PMID- 29190156
TI  - Medication-assisted treatment for youth with opioid use disorder: Current
      dilemmas and remaining questions.
AB  - The prevalence of risky opioid use, opioid use disorder, and related harms
      continue to rise among youth (adolescents and young adults age 15-25) in North
      America. With an increasing number of opioid overdoses, there remain significant
      barriers to care for youth with opioid use disorder, and there is an urgent need
      to expand evidence-based care for treatment of opioid use disorder among this
      population. Based on the extensive literature on treatment of opioid use disorder
      among adults, medicated-assisted treatment is likely to be an important or even
      essential component of treatment of opioid use disorder for most youth. In this
      article, we outline the current dilemmas and questions regarding the use of
      medication-assisted treatment among youth with opioid use disorder and propose
      some potential solutions based on the current evidence.

PMID- 29190157
TI  - Factors influencing secondary care pharmacist and nurse independent prescribers'
      clinical reasoning: An interprofessional analysis.
AB  - In the United Kingdom, pharmacist and nurse independent prescribers are
      responsible for both the clinical assessment of and prescribing for patients.
      Prescribing is a complex skill that entails the application of knowledge, skills,
      and clinical reasoning to arrive at a clinically appropriate decision. Decision
      making is influenced and informed by many factors. This study, the first of its
      kind, explores what factors influence pharmacist and nurse independent
      prescribers during the process of clinical reasoning. A think-aloud methodology
      immediately followed by a semi-structured interview was conducted with 11 active
      nurse and 10 pharmacist independent prescribers working in secondary care. Each
      participant was presented with validated clinical vignettes for the think-aloud
      stage. Participants chose the clinical therapeutic areas for the vignettes, based
      on their self-perceived competencies. Data were audio-recorded, transcribed
      verbatim, and a constant-comparative approach was used for analysis. Influences
      on clinical reasoning were broadly categorised into themes: social interaction,
      intrinsic, and contextual factors. These themes showed that intrinsic,
      sociocultural, and contextual aspects heavily influenced the clinical reasoning
      processes of prescribers. For example, prescribers were aware of treatment
      pathways, but chose to refer patient cases to avoid making the final prescribing
      decision. Exploration of this behaviour in the interviews revealed that previous
      experience and attitudes such as confidence and cautiousness associated with
      responsibility were strong influencers within the decision-making process. In
      addition, strengthening the professional identity of prescribers could be
      achieved through collaborative work with interprofessional healthcare teams to
      orient their professional practice from within the profession. Findings from this
      study can be used to inform the education, training, and practice of independent
      prescribers to improve healthcare services by improving their professional and
      interprofessional development.

PMID- 29190158
TI  - Integrating Interprofessional Education and Cultural Competency Training to
      Address Health Disparities.
AB  - PROBLEM: Many U.S. medical schools have accreditation requirements for
      interprofessional education and training in cultural competency, yet few programs
      have developed programs to meet both of these requirements simultaneously.
      Furthermore, most training programs to address these requirements are broad in
      nature and do not focus on addressing health disparities. The lack of integration
      may reduce the students' ability to apply the knowledge learned. Innovative
      programs that combine these two learning objectives and focus on disenfranchised
      communities are needed to train the next generation of health professionals.
      INTERVENTION: A unique interprofessional education program was developed at the
      University of Arkansas for Medical Sciences Northwest. The program includes
      experiential learning, cultural exposure, and competence-building activities for
      interprofessional teams of medicine, nursing, and pharmacy students. The
      activities include (a) educational seminars, (b) clinical experiential learning
      in a student-led clinic, and (c) community-based service-learning through health
      assessments and survey research events. CONTEXT: The program focuses on
      interprofessional collaboration to address the health disparities experienced by
      the Marshallese community in northwest Arkansas. The Marshallese are Pacific
      Islanders who suffer from significant health disparities related to chronic and
      infectious diseases. OUTCOME: Comparison tests revealed statistically significant
      changes in participants' retrospectively reported pre/posttest scores for
      Subscales 1 and 2 of the Readiness for Interpersonal Learning Scale and for the
      Caffrey Cultural Competence in Healthcare Scale. However, no significant change
      was found for Subscale 3 of the Readiness for Interpersonal Learning Scale.
      Qualitative findings demonstrated a change in students' knowledge, attitudes, and
      behavior toward working with other professions and the underserved population.
      LESSONS LEARNED: The program had to be flexible enough to meet the educational
      requirements and class schedules of the different health professions' education
      programs. The target community spoke limited English, so providing interpretation
      services using bilingual Marshallese community health workers was integral to the
      program's success.

PMID- 29190159
TI  - Performance of Bio-Occlusive Dressing as Barrier Protection from Presurgical
      Chlorhexidine Skin Preparation.
AB  - : Purpose/Aim of the study: Chlorhexdine has been shown to provide excellent and
      cost-effective presurgical antisepsis. However, standard presurgical
      concentrations of chlorhexidine (2-4%) are known to cause ocular injury, even in
      cases in which a bio-occlusive dressing (TegadermTM) was applied beforehand to
      the closed eye. MATERIALS AND METHODS: Three experiments were conducted to assess
      the barrier performance of TegadermTM to chlorhexidine skin prep in vitro and on
      non-ocular skin. The experiments used water as a control group. RESULTS: In the
      first in vitro experiment, the chlorhexidine group showed penetration at the
      edges of the TegadermTM at 5 minutes while the water (control) group never
      penetrated the TegadermTM. A subsequent experiment testing the central
      permeability of the tegaderm showed it to be impermeable to both chlorhexidine
      and water after 90 minutes. In the in vivo experiment, the chlorhexidine group
      showed penetration at 10 minutes, while the water (control) group never
      penetrated the TegadermTM. CONCLUSIONS: These data suggest TegadermTM is
      permeable at the edges to chlorhexidine but not water. Based on this, along with
      reports of ocular injury from chlorhexidine skin preparation of the head despite
      prior application of TegadermTM over the eyes, we advise against using bio
      occlusive adhesive dressing to protect the ocular surface from chlorhexidine
      exposure. We suggest an alternative presurgical antiseptic agent such as povidone
      iodine be employed whenever possible.

PMID- 29190160
TI  - Clinical Profile, Ultra-Wide-Field Fluorescence Angiography Findings, and Long
      Term Prognosis of Uveitis in Tubulointerstitial Nephritis and Uveitis Syndrome at
      One Tertiary Medical Institute in China.
AB  - PURPOSE: To analyze the clinical features and long-term prognosis of uveitis in
      tubulointerstitial nephritis and uveitis (TINU) syndrome in a cohort of Chinese
      patients. METHODS: A total of 32 patients with TINU syndrome between 2000 - 2016
      were analyzed retrospectively. RESULTS: Mild anterior inflammation was observed
      in all cases. Ultra-wide-field fluorescence angiography (UWFA) was conducted on
      13 patients, and peripheral vascular leakage was observed in 22/26 eyes (84.62%)
      compared with active anterior chamber inflammation in 13/26 eyes (50%). Three
      patients received increased corticosteroid dosage therapy on their first episode
      of uveitis guided by UWFA had stopped steroids without recurrence. CONCLUSION:
      The uveitis in TINU syndrome was mild. Corticosteroids were efficient in most
      cases, but a slower tapering and long-term treatment were required. UWFA is
      sensitive in detecting the activity of uveitis and might be useful in monitoring
      disease progression. Complete withdrawal of medication was difficult to achieve
      in some cases.

PMID- 29190161
TI  - In response to: Smit D, Meyer D, Maritz J, et al. "Polymerase Chain Reaction and
      Goldmann-Witmer Coefficient to Examine the Role of Epstein-Barr Virus in
      Uveitis".

PMID- 29190162
TI  - Redefining treatment failure for pediatric acute leukemia in the era of minimal
      residual disease testing.
AB  - Technologies for the detection of minimal residual disease (MRD) in leukemia and
      our understanding of the prognostic implications of MRD at different phases of
      treatment have significantly improved over the past decade. As a result,
      definitions of treatment failure based on bone marrow morphology by light
      microscopy are becoming increasingly inadequate for clinical care and trial
      design. In addition, novel therapies that may have increased efficacy and
      decreased toxicity in the setting of MRD compared to overt disease are changing
      clinical practice and challenging investigators to redefine treatment failure,
      the role of disease surveillance in remission, and clinical trial eligibility in
      the era of MRD.

PMID- 29190165
TI  - Challenging Treatment of Ocular Surface Squamous Neoplasia in Patients with
      Atopic Disease.
AB  - PURPOSE: Few studies have described ocular surface squamous neoplasia (OSSN) and
      its association with atopic diseases and there is no consensus on the course of
      OSSN in atopic patients. We thereby report three patients with atopy and OSSN.
      METHODS: Retrospective case series. RESULTS: Three male patients with mean age of
      73 presented with OSSN and history of atopy treated with immunosuppressant
      therapy. Their histories included atopic dermatitis and keratoconjunctivitis. All
      patients had treatment complicated by multiple surgeries, recurrences, or
      advanced disease. The patients initially received medical treatment with topical
      interferon-alpha-2b (IFNalpha2b). However, all the patients had recurrences and
      required modification of treatment including topical 5-fluorouracil (5-FU).
      CONCLUSION: We report on three patients with a history of atopy whose OSSN
      presentation and course was challenging. Overall, our cases responded better to
      topical 5-fluorouracil compared to topical interferon-alpha-2b, but recurrences
      were common. These patients may benefit from more aggressive and long-term
      treatment.

PMID- 29190164
TI  - Investigating the biology of relapsed acute leukemia: Proceedings of the
      Therapeutic Advances for Childhood Leukemia & Lymphoma (TACL) Consortium Biology
      Working Group.
AB  - During the 2016 Therapeutic Advances for Childhood Leukemia & Lymphoma (TACL)
      Consortium investigators' meeting (Los Angeles, CA), a Biology Working Group was
      established to support the consortium's mission of developing innovative
      therapies for currently incurable childhood leukemias and lymphomas. The charge
      of the Biology Working Group was to address how TACL could advance biological
      investigations of pediatric relapsed/refractory hematologic malignancies while
      undertaking forward-looking therapeutic trials. To this end, the TACL Biology
      Committee was established to provide the scientific platform needed to further
      develop preclinical and translational studies that will advance the understanding
      and treatment of relapsed and refractory disease. The Biology Committee will
      focus on ensuring state-of-the-art studies that address biological components of
      early phase clinical trials, and developing a central biology bank of materials
      from these early phase trials for interrogations into the mechanisms of disease
      resistance.

PMID- 29190166
TI  - Non-alcoholic fatty liver disease (NAFLD) models in drug discovery.
AB  - INTRODUCTION: The progressive disease spectrum of non-alcoholic fatty liver
      disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is a
      rapidly emerging public health crisis with no approved therapy. The diversity of
      various therapies under development highlights the lack of consensus around the
      most effective target, underscoring the need for better translatable preclinical
      models to study the complex progressive disease and effective therapies. Areas
      covered: This article reviews published literature of various mouse models of
      NASH used in preclinical studies, as well as complex organotypic in vitro and ex
      vivo liver models being developed. It discusses translational challenges
      associated with both kinds of models, and describes some of the studies that
      validate their application in NAFLD. Expert opinion: Animal models offer
      advantages of understanding drug distribution and effects in a whole body
      context, but are limited by important species differences. Human organotypic in
      vitro and ex vivo models with physiological relevance and translatability need to
      be used in a tiered manner with simpler screens. Leveraging newer technologies,
      like metabolomics, proteomics, and transcriptomics, and the future development of
      validated disease biomarkers will allow us to fully utilize the value of these
      models to understand disease and evaluate novel drugs in isolation or
      combination.

PMID- 29190167
TI  - Engaging the Transgender Community to Improve Medical Education and Prioritize
      Healthcare Initiatives.
AB  - : Phenomenon: Transgender patients experience discrimination, limited access to
      care, and inadequate provider knowledge in healthcare settings. Medical education
      to address transgender-specific disparities is lacking. Research that engages
      transgender community members may help address health disparities by empowering
      patients, increasing trust, and informing medical curricula to increase
      competence. APPROACH: A 2015 Community Forum on Transgender Health Care was
      hosted at the University of Louisville School of Medicine, which included
      healthcare professionals and transgender community members to facilitate dialogue
      among mixed-participant groups using a World Cafe model. Fifty-nine participants
      discussed the status of transgender healthcare and made recommendations for local
      improvements. A follow-up survey was administered to 100 individuals, including
      forum participants and their referrals. The forum discussion and survey responses
      were analyzed to determine common perceptions of transgender healthcare,
      priorities for improvement interventions, and themes to inform curriculum.
      FINDINGS: The community forum discussion showed that local transgender care is
      overwhelmingly underdeveloped and unresponsive to the needs of the transgender
      community. The follow-up survey revealed that priorities to improve transgender
      care included a multidisciplinary clinic for lesbian, gay, bisexual, and
      transgender (LGBT) patients, an LGBT-friendly network of physicians, and more
      training for providers and support staff. This mutually constructive engagement
      experience influenced reform in undergraduate curricula and continuing education
      opportunities. Insights: Community engagement in healthcare disparities research
      can cultivate improbable discussions, yield innovative insight from marginalized
      populations, and build relationships with community members for future
      collaborations and interventions. Societal acceptance of transgender identities,
      which could be promoted through healthcare providers, could stimulate significant
      progress in transgender healthcare. Supplemental educational interventions for
      practicing physicians will improve the current conditions of transgender
      healthcare, but a comprehensive medical school curriculum specifically for
      transgender health that includes interactions between the transgender community
      and medical students could be particularly impactful.

PMID- 29190168
TI  - The effect of anti-thyroid antibodies positivity on children with primary immune
      thrombocytopenia.
AB  - Primary immune thrombocytopenia (ITP) is the most common cause of acquired
      thrombocytopenia in children. Anti-thyroid antibodies (aTA) have previously been
      found to be present in various autoimmune diseases. Our aim was to study the
      effect of aTA positivity (which are anti-thyroid peroxidase (aTPo) and/or anti
      thyroglobulin (aTg)) on children with primary immune thrombocytopenia and their
      relation to treatment response. Sixty-one children with primary ITP were enrolled
      in the present study. They were further subdivided into: ND&P group (newly
      diagnosed and persistent) and chronic ITP group. Seventy-five apparently healthy
      children were enrolled as control group. aTPo and aTg antibodies were
      significantly higher and more frequently positive in all children with ITP and in
      each ITP group than the control group (P <.05 in all). But, there were no
      statistically significant differences between the two ITP subgroups (P >.05). aTA
      positive children with ITP had significantly lower platelet count: at the start
      of treatment (P =.009), after receiving methylprednisolone or intravenous
      immunoglobulin (P =.02) and at one month follow-up (P =.003) than aTA negative
      children with ITP. Lastly, aTA positive children had more relapses (P =.03),
      continued more frequently to have relapses after one year in the ND&P group (P
      =.02) and required immunosuppressive therapy more frequently in the chronic ITP
      group (P =.005).

PMID- 29190169
TI  - TACL'ing supportive care needs in pediatric early phase clinical trials for acute
      leukemia: A report from the therapeutic advances in childhood leukemia & lymphoma
      (TACL) consortium supportive care committee.
AB  - A Supportive Care Committee was recently developed within the Therapeutic
      Advances in Childhood Leukemia & Lymphoma (TACL) Consortium. This was
      substantiated by the significantly high rate of serious adverse events (SAE)
      (CTCAE Grade >=3 toxicity) experienced by patients with relapse/refractory acute
      leukemia enrolled on our phase I trials. Such treatment-related toxicity has
      resulted in patients being removed from study and thus potentially not receiving
      clinical benefit from the novel therapy. In addition, increased treatment-related
      toxicity may compromise new agents from moving forward in their clinical
      development. To address these challenges, TACL initiated a Supportive Care
      Committee to help mitigate the treatment-related toxicity risk that exists in
      heavily pre-treated patients with relapse/refractory leukemia. This manuscript
      reviews the mission of the TACL Supportive Care Committee presented at the 2016
      TACL Investigators' Meeting (Los Angeles, CA) and the future direction in
      providing enhanced supportive care guidelines for all TACL studies.

PMID- 29190170
TI  - The Role of Dexamethasone Implant in the Management of Tubercular Uveitis.
AB  - PURPOSE: To study the safety and efficacy of intravitreal injection of
      dexamethasone implant in the management of posterior segment involvement in
      tubercular uveitis (TBU). METHODS: In this study, retrospective analysis of
      safety and efficacy of intravitreal injection of dexamethasone implant for
      various indications such as cystoid macular edema (CME), vitritis, or paradoxical
      worsening in TB-related intermediate uveitis, retinal vasculitis, and multifocal
      serpiginoid choroiditis (MSC) was performed. RESULTS: The study included 17
      patients (19 eyes; 7 males). IOP increased from 14.88 +/- 2.68 mm Hg to 16.4 +/-
      5.82 mm Hg (p = 0.18) at 3 months. BCVA improved from 0.37 +/- 0.35 to 0.27 +/-
      0.21 at 3 months (p = 0.03). CME resolved at 3 months and two patients with
      paradoxical worsening showed resolution within 1 month. CONCLUSION: Intravitreal
      dexamethasone implant is safe and efficacious as an adjunct to ATT in reducing
      the central macular thickness, vitritis, and progression of choroiditis lesions
      in paradoxical worsening of MSC.

PMID- 29190171
TI  - Associations with retinal vascular occlusions in a diverse, urban population.
AB  - PURPOSE: Retinal vascular occlusions can lead to sudden and permanent visual
      impairment or blindness. Few epidemiological studies on retinal vascular
      occlusions have been conducted, especially on diverse populations. METHODS: This
      is a retrospective case-control study of all incident retinal vascular occlusions
      occurring during a three and one-half year study period at Montefiore Medical
      Center, capturing all potential cases by diagnosis codes. Patients with retinal
      venous occlusions (RVO) and retinal arterial occlusions (RAO) were analyzed
      separately and compared to age-matched control groups. RESULTS: All potential
      charts (n = 700) were reviewed, confirming 214 RVO and 35 RAO incident cases. In
      multivariable analyses, RVO was associated with type 2 diabetes mellitus (OR
      2.41, p < 0.001), history of cerebrovascular accident (OR 2.14, p = 0.011),
      hypertension (OR 1.83, p = 0.004), glaucoma (OR 6.91, p < 0.001), black race (OR
      3.72, p < 0.001), and male gender (OR 2.19 p < 0.001). RAO was significantly
      associated with current and former smoking combined (OR 8.95, p = 0.021) and male
      gender (OR 2.56, p = 0.038). CONCLUSION: Cardiovascular risk factors and glaucoma
      are reaffirmed as significant predictors of retinal vascular occlusions in a
      diverse patient population. Retinal vascular occlusions are more common in
      certain races and ethnicities, and further study into this may help identify high
      risk individuals based on demographics.

PMID- 29190172
TI  - Implementation of a "real world" School-Based Asthma Therapy program targeting
      urban children with poorly controlled asthma.
AB  - OBJECTIVE: Describe implementation and clinical impact of a "real world" School
      Based Asthma Therapy (SBAT) Program serving an urban, largely Medicaid population
      in a large midwestern city in the United States. METHODS: A retrospective,
      descriptive evaluation of SBAT was conducted. Students were referred by school
      nurses or providers, enrolled throughout the year, and could reenroll in
      subsequent years. A total of 286 students participated in the 2015-2016 school
      year. Kruskal-Wallis nonparametric testing compared Asthma Control TestTM (ACT)
      scores from enrollment (anytime between 2013 and 2015) to 2015-2016 for 198
      students; and pre- and postenrollment asthma-related emergency department (ED),
      inpatient, and critical care (pediatric intensive care unit or PICU) utilization
      rates (events/student/year) for 98 students enrolled for a full year. RESULTS:
      SBAT participation grew from 17 to 131 schools and from 38 to 268 students
      between 2013-2014 and 2015-2016. Mean ACT scores increased from 16.2 (SD = 4.89)
      to 21.37 (SD = 3.41) (K-W chi2 = 35.45, p = 0.008). Healthcare utilization rates
      from 1-year preenrollment to 1-year postenrollment decreased for ED (0.91-0.44; K
      W chi2 = 18.61, p = 0.0002) and Inpatient (0.38-0.10; K-W chi2 = 7.68, p = 0.02).
      Reduction in PICU (0.27-0.02) was not statistically significant. CONCLUSIONS:
      SBAT, modeled after programs shown in controlled trials to improve asthma health
      markers ( 1-3 ), was successfully implemented in economically challenged, urban
      schools. Rapid growth and patient reenrollment reflect program acceptance by
      schools, providers, and caregivers. Improved ACT scores and healthcare
      utilization supported program efficacy. SBAT could be one solution to improved
      asthma control in underserved school-aged pediatric patients.

PMID- 29190173
TI  - Detection of Bacteria Colonizing Titanium Spinal Implants in Children.
AB  - BACKGROUND: Bacterial colonization of spinal implants may cause severe
      complications in patients with early-onset scoliosis. Correct diagnosis and
      detection of microbiologic formation is crucial to prevent delayed infections
      caused by bacterial colonization. The purposes of this study were to estimate the
      rate and risk factors of colonization of vertical expandable prosthetic titanium
      rib (VEPTR) implants in children and to compare the different methods for
      detecting microbiologic formation on the spinal implants. METHODS: We evaluated
      prospectively a group of 42 children with spinal deformities with an overall of
      95 lengthening surgeries and applied different methods to detect potential
      bacterial colonization of VEPTR implants: swab of the implant, swab with culture
      of tissue, analysis of the removed lock, polymerase chain reaction (PCR), and
      confocal microscopy. Potential risk factors were evaluated. RESULTS: Of 42
      patients, 17 (40%) were rated positive for bacterial colonization with
      Propionibacterium acnes and coagulase-negative staphylococci being the most
      commonly found bacteria. Risk factors for colonization were increasing age, body
      height, and weight. The swab with culture of removed tissue yielded most positive
      results, whereas direct microscopy and PCR were the least sensitive detection
      methods. Furthermore, commonly used infectious blood parameters were
      inconclusive. CONCLUSIONS: Although the impact of bacterial colonized implants on
      the health of the patients is not fully elucidated, clinicians aim for prevention
      of microbiologic formation on implanted devices. Therefore, reliable,
      inexpensive, and easy to apply diagnostic tools are indispensable to detect
      colonization. Based on our data, the swab together with tissue culture has the
      potential to become the method of choice for future diagnosis.

PMID- 29190174
TI  - Same-Sex Friendship, School Gender Composition, and Substance Use: A Social
      Network Study of 50 European Schools.
AB  - BACKGROUND: Other-sex friendship (girls with boy friends, boys with girl friends)
      has been associated with substance use, but how the gender composition of schools
      influences substance use has not been known. OBJECTIVES: We analyzed the
      influence of other-sex friendship on substance use and took into account the
      proportion of each gender group at the schools, and hypothesized that other-sex
      friendship is associated with higher levels of substance use and that schools
      with a majority of males have higher levels of use than female-majority schools.
      METHODS: In 2013, a social network survey was carried out in six European cities.
      In each city, schools were selected and 11,015 adolescents (aged 14-16) were
      recruited (participation rate = 79.4%). We collected data on smoking, binge
      drinking, cannabis use, and peer group composition. RESULTS: Other-sex friendship
      was associated with smoking, binge drinking, and cannabis use for girls and with
      smoking for boys. Substance use was more frequent in schools with a majority of
      males. Conclusions/Importance: Adolescent girls are best protected from substance
      use if they are in gender-balanced schools, but in same-sex friendship. This
      offers new perspectives on gender mixing at school. In schools with a majority of
      boys, more attention should be paid to girls, and gender-specific health
      promotion programs should be implemented. This European study is the first to
      take into account both individual (other-sex friendship) and contextual (gender
      composition of schools) gender interactions. It confirms previous studies on
      other-sex friendship, while shedding light on the influence of gender-normative
      contexts on substance use.

PMID- 29190175
TI  - Going beyond prescription pain relievers to understand the opioid epidemic: the
      role of illicit fentanyl, new psychoactive substances, and street heroin.
AB  - The opioid epidemic is associated with morbidity and mortality, and it has taken
      a vast toll on American society. While prescription opioid abuse is part of the
      opioid problem, it is by no means the entirety of it. Opioid abuse appears to
      have entered a technology-driven new world of clandestine labs all over the globe
      and many new synthetic analog, counterfeit, and adulterated drugs that arrive via
      the internet faster than the Drug Enforcement Administration (DEA) can catalog
      and outlaw them. To deal with opioid abuse, it must be recognized that it is more
      - far more - than a subset of chronic pain patients who become addicted. Indeed,
      to reduce the opioid epidemic to this population is to misunderstand it. The
      opioid epidemic involves illicit opioids, counterfeit opioids, new psychoactive
      substances, diverted opioids, and prescription opioids. The objective of this
      narrative review is to consider the roles of all substances that contribute to
      the opioid epidemic in America.

PMID- 29190176
TI  - Correlation of serum ferritin levels with hepatic MRI T2 and liver iron
      concentration in nontransfusion beta-thalassemia intermediate patients: A
      contemporary issue.
AB  - BACKGROUND: Beta-thalassemia intermediate is a genetic disease that is milder
      than beta-thalassemia major. The T2* magnetic resonance imaging (MRI) technique
      is currently the gold standard for iron load detection. However, it is expensive
      and needs an expert radiologist to report findings. Therefore, we conducted this
      study to determine an optimal cut-off value of ferritin in proportion to T2 MRI
      of liver and measurement of liver iron concentration for early detection of
      hepatic iron overload in Beta-thalassemia intermediate patients. METHODS: This
      cross-sectional study was conducted on 108 patients with Beta-thalassemia
      intermediate who referred to tertiary hospital, Shiraz, Iran. Serum ferritin,
      hepatic T2 MRI, and liver iron concentration were assessed. Receiver operator
      characteristic was used to determine the sensitivity and specificity of cut-off
      value. RESULTS: Serum ferritin levels showed a statistically significant negative
      correlation with T2 hepatic MRI (r = -0.290, p value =.003) and positive
      correlation with liver iron concentration (r = 0.426, p value <.001) in the
      patients with Beta-thalassemia intermediate. According to the receiver operator
      characteristic, the best cut-off value for ferritin to show early diagnosis of
      liver iron overload was 412 ng/mL. Calculated sensitivities and specificities
      were 0.78 and 0.82 for T2 MRI and 0.76 and 0.86 for liver iron concentration,
      respectively. CONCLUSION: Serum ferritin levels of around 450 ng/mL might be
      considered as a cut-off point to evaluate hepatic iron overload before using
      expensive, not readily available T2 MRI. This level of serum ferritin could be
      considered for starting iron chelation therapy in patients with Beta-thalassemia
      intermediate in areas where T2 MRI is not available.

PMID- 29190178
TI  - Transanal Total Mesorectal Excision in Lower Rectal Cancer: Comparison of Short
      Term Outcomes with Conventional Laparoscopic Total Mesorectal Excision.
AB  - BACKGROUND: Transanal total mesorectal excision (TaTME) is a novel technique to
      treat rectal cancer and also to obtain good-quality specimens. This study
      investigated the clinical results and perioperative and pathological outcomes of
      TaTME in lower rectal cancer treatment in comparison with laparoscopic total
      mesorectal excision (LaTME). METHODS: During January 2014 to May 2017, all
      consecutive patients with lower rectal cancer who underwent TaTME were
      identified. This cohort study was matched for age, gender, American Society of
      Anesthesiology (ASA) score, and clinical staging with a cohort of patients who
      underwent conventional LaTME. RESULTS: A total of 46 patients were analyzed in
      both groups. There were no significant differences in baseline characteristics
      between the groups. The estimated blood loss, duration of operation, and
      postoperative complications were also not different between both groups.
      Regarding pathological outcomes, no patients with circumferential margin (CRM) <1
      mm were observed in the TaTME group compared to 4 patients with CRM <1 mm in the
      LaTME group (P = .037). CONCLUSION: TaTME is a safe and feasible procedure in
      this matched case-control study. TaTME had better pathological outcomes with CRM
      uninvolvement compared with laparoscopic surgery.

PMID- 29190179
TI  - Patient-Reported Health-Related Quality-of-Life Assessment at the Point-of-Care
      with Adolescents and Young Adults with Cancer.
AB  - PURPOSE: Advances in health-related quality-of-life (HRQL) measurement enable
      point-of-care assessments. We incorporated the Patient-Reported Outcomes
      Measurement Information System (PROMIS(r)) Global Health Scale in routine
      outpatient evaluations of adolescent and young adult (AYA) oncology patients and
      survivors at two geographically distinct U.S. institutions. METHODS: AYAs (18-39
      years old) completed the 10-question PROMIS Global. Summary subscale scores for
      Global Physical Health (GPH) and Global Mental Health (GMH) were produced using
      established scoring algorithms (standardized mean = 50, standard deviation = 10).
      In addition to comparisons by treatment status, associations between lower
      subscale scores (<45, previously defined as clinically meaningful) and patient
      characteristics were assessed using two-sample t-tests among those off treatment.
      RESULTS: Of 147 patients approached, 142 consented. Mean age was 24.6 +/- 5.3
      years; 53.5% were male; and 61.3% had hematologic malignancies. Most (76%) were
      off treatment; 43.0% had treatment complications. While mean GPH and GMH scores
      did not differ from the standardized population mean (GPH, 49.7 +/- 8.8, p =
      0.73; GMH, 50.5 +/- 9.3, p = 0.55), mean GPH scores were lower among those on
      treatment (44.3 +/- 9.0) than off treatment (51.5 +/- 8.1, p < 0.0001). There was
      no difference in GMH scores by treatment status. Among those off treatment, 26.9%
      of GPH and 22.2% of GMH scores were <45. The only factor associated with lower
      GPH scores was treatment complications; no factors were associated with lower GMH
      scores. CONCLUSION: Point-of-care HRQL assessment with AYAs is feasible. Among
      patients off treatment, GPH scores were lower for patients with treatment
      complications. Further research is needed to understand factors associated with
      lower GMH scores in this AYA oncology population.

PMID- 29190180
TI  - Daily-level Associations between Negative Mood, Perceived Stress, and College
      Drinking: Do Associations Differ by Sex and Fraternity/Sorority Affiliation?
AB  - BACKGROUND: Individuals experiencing elevated negative mood and stress may drink
      to self-medicate, yet daily-level evidence for these associations is mixed.
      OBJECTIVE: To clarify daily associations between negative mood and perceived
      stress with alcohol use among high-risk college students and test whether these
      associations may vary by same-day versus next-day drinking, sex, and
      fraternity/sorority affiliation. METHODS: Frequently drinking college students (n
      = 347) participated in a daily diary study, which included daily morning and
      evening assessments that occurred for two weeks in four consecutive academic
      quarters. Multilevel zero-inflated Poisson regressions were conducted to examine
      the effects of daily negative mood and perceived stress on same-day and next-day
      drinking. RESULTS: Students with higher average negative mood and perceived
      stress across the sampled days reported a lower likelihood of drinking.
      Examination of daily-level associations showed that on days students experienced
      elevated negative mood and perceived stress, they were less likely to drink any
      alcohol the same day. However, days with elevated negative mood were associated
      with greater alcohol use the next day. Tests of cross-level interactions
      indicated that four daily-level associations between higher negative mood or
      perceived stress and reductions in drinking were found to be significant among
      females and students unaffiliated with fraternity/sorority only.
      Conclusions/Importance: Among high-risk college drinkers, negative mood and
      perceived stress were associated with decreased risk of drinking, particularly
      among females and students unaffiliated with fraternity/sorority. Daily
      elevations in negative mood may lead to drinking on a subsequent day and the
      reason for this lagged effect warrants future research.

PMID- 29190181
TI  - Identifying opportunities to bridge disparity gaps in curing childhood cancer in
      Malawi: Malignancies with excellent curative potential account for the majority
      of diagnoses.
AB  - The majority of African children with cancer die without access to resources. We
      describe efforts to build a public treatment program with curative intent for
      childhood cancer in Lilongwe, Malawi despite severe limitations in diagnostic and
      therapeutic resources. We retrospectively analyzed a cohort of childhood cancer
      patients at Kamuzu Central Hospital from 12/2011-6/2013. Consistently available
      chemotherapeutic agents were limited to cyclophosphamide, vincristine,
      doxorubicin, bleomycin, methotrexate, and prednisone. Of 258 newly diagnosed
      childhood malignancies, 17 patients with retinoblastoma were excluded from
      clinical analyses due to insufficient clinical data. Among the remainder of the
      cohort (n = 241), 42% were female with median age 8.4 years (range 0.6-17.9).
      Forty-six (19%) were HIV-infected (42 Kaposi sarcoma, 3 Burkitt lymphoma, 1
      Hodgkin lymphoma). The most common clinical presentations were palpable abdominal
      mass (41%), peripheral lymphadenopathy (33%), and jaw mass (17%). Nearly two
      thirds of total diagnoses were accounted for by Burkitt lymphoma (n = 74), Kaposi
      sarcoma (n = 52), Hodgkin lymphoma (n = 21), and Wilms tumor (n = 19). Twelve
      month overall survival for these 4 most common diagnoses was 54% (95% confidence
      interval 46-61) versus 19% (95% confidence interval 11-30) for all other
      diagnoses (median follow-up 19 months). Treatment-related mortality was highest
      in patients with non-Wilms solid tumors of the abdomen (48% versus 10% for the
      overall cohort, p < 0.001), while treatment abandonment was highest in patients
      with bone and soft-tissue sarcomas (29% versus 14% overall, p = 0.05). Childhood
      cancers with excellent curative potential accounted for the majority of patients,
      establishing an opportunity to build treatment programs with curative intent
      despite severe limitations.

PMID- 29190182
TI  - Checkpoint inhibition in pediatric hematologic malignancies.
AB  - Immune surveillance comprising of adaptive and innate immune systems is naturally
      designed to eliminate cancer development; overexpression of inhibitory receptors
      and their ligands prevent this check and lead to evasion and hence cancer
      progression and metastasis. The use of tumor-specific monoclonal antibodies
      (MAbs) targeting these checkpoint regulators is promising and has led to this
      novel field of cancer immunotherapy. The first antibody directed against
      cytotoxic T-lymphocyte associated protein 4 (CTLA-4), ipilimumab, showed
      promising results in clinical trials and was approved by the US Food and Drug
      Administration (FDA) for the treatment of metastatic melanoma in 2011. Since
      then, various other immune checkpoint inhibitors are being studied in preclinical
      and clinical trial phases, targeting programmed-death-1 (PD-1) and its ligand
      programmed death ligand 1 (PD-L1), T cell lymphocyte activation gene-3 (LAG-3),
      and others. Results from clinical trials are promising, and currently this
      approach has proven effective and safe in patients with solid tumors and some
      hematological malignancies in adults. In general, CTLA-4 and PD-1 inhibitors are
      well tolerated; however, the augmented immune response enabled by this class of
      agents is associated with a unique group of side effects called immune-related
      adverse events (irAEs). Experience in pediatrics using immune checkpoint
      inhibitors for hematological malignancies is limited to Hodgkin's disease and non
      Hodgkin's lymphoma as in the ongoing Children's Oncology Group (COG) protocol
      ADVL1412. Therapeutic advances in childhood leukemia and lymphoma (TACL)
      consortium will initiate an early phase clinical trial with PD-1 inhibitor
      nivolumab in relapsed/refractory acute myeloid leukemia (AML) in the next few
      months.

PMID- 29190183
TI  - A Long-Term Follow-Up of a New Surgery Method: Laparoscope-Assisted Heart-Shaped
      Anastomosis for Hirschsprung's Disease.
AB  - BACKGROUND: Laparoscopic surgery is widely used in the treatment of
      Hirschsprung's disease (HD). However, constipation and soiling are still the main
      long-term complications. A new type of anastomosis, which is characterized by a
      heart-shaped colorectal anastomosis after splitting the posterior rectum wall to
      0.5 cm above the dentate line, has been improved by our medical center. The
      purpose of this study was to determine the long-term effects of laparoscope
      assisted heart-shaped anastomosis (LHSA) and to compare it with a more generally
      applied approach, the laparoscope-assisted Soave procedure (LSP). PATIENTS AND
      METHODS: In this retrospective study, we investigated the symptoms of chronic
      constipation and soiling in 56 patients after LHSA and 54 patients after LSP
      between 2005 and 2011. RESULTS: For LHSA, the median age at surgery was 1.4 years
      (0.2-7.3), and the median follow-up time was 7.1 years (5-11.3). For LSP, the
      median age at surgery was 1.2 years (0.1-6.2) and the median follow-up time was
      7.0 years (5-9.3). Constipation was less frequent after LHSA than after LSP (7.1
      versus 22.2%, P = .025), but there was no difference in the frequency of soiling
      after LHSA compared with that after LSP (8.9 versus 14.8%, P = .339).
      CONCLUSIONS: The improved anastomosis (LHSA) preserves most of the internal anal
      sphincter, and the wide anastomosis prevents stenosis as well. In the long-term
      follow-up results, the incidence of constipation after LHSA declined when
      compared with that after LSP, and soiling showed a satisfactory result. Our
      medical center has performed laparotomy-assisted heart-shaped anastomosis since
      the 1990s and LHSA since the 2000s. Because it is easy to learn and provide good
      outcomes, many medical centers in China have adopted the heart-shaped anastomosis
      to treat HD. Using the LHSA method to manage the affected bowel provides
      satisfactory long-term outcomes, that is, avoiding constipation and soiling.
      Thus, LHSA may provide a new choice for HD operations.

PMID- 29190186
TI  - Influence of Speed and Accuracy Constraints on Motor Learning for a Trajectory
      Based Movement.
AB  - This study investigated the influences of task constraint on motor learning for a
      trajectory-based movement considering the speed-accuracy relationship. In the
      experiment, participants practiced trajectory-based movements for five
      consecutive days. The participants were engaged in training with time
      minimization or time-matching constraints. The results demonstrated that the
      speed-accuracy tradeoff was not apparent or was weak in the training situation.
      When the participants practiced the movement with a time-minimization constraint,
      movement errors did not vary, whereas the movement time decreased. With the time
      matching constraint, the errors decreased as a session proceeded. These results
      were discussed in terms of the combination of signal-dependent noises and
      exploratory search noises. It is suggested that updating spatial and temporal
      factors does not appear to occur simultaneously in motor learning.

PMID- 29190187
TI  - Characterization of inter-tissue and inter-strain variability of TCE glutathione
      conjugation metabolites DCVG, DCVC, and NAcDCVC in the mouse.
AB  - Trichloroethylene (TCE) is a ubiquitous environmental toxicant that is a liver
      and kidney carcinogen. Conjugation of TCE with glutathione (GSH) leads to
      formation of nepthrotoxic and mutagenic metabolites postulated to be critical for
      kidney cancerdevelopment; however, relatively little is known regarding their
      tissue levels as previous analytical methods for their detection lacked
      sensitivity. Here, an LC-MS/MS-based method for simultaneous detection of S-(1,2
      dichlorovinyl)-glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N
      acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC) in multiple mouse tissues was
      developed. This analytical method is rapid, sensitive (limits of detection (LOD)
      3-30 fmol across metabolites and tissues), and robust to quantify all three
      metabolites in liver, kidneys, and serum. The method was used to characterize
      inter-tissue and inter-strain variability in formation of conjugative metabolites
      of TCE. Single oral dose of TCE (24, 240 or 800 mg/kg) was administered to male
      mice from 20 inbred strains of Collaborative Cross. Inter-strain variability in
      the levels of DCVG, DCVC, and NAcDCVC (GSD = 1.6-2.9) was observed. Whereas
      NAcDCVC was distributed equally among analyzed tissues, highest levels of DCVG
      were detected in liver and DCVC in kidneys. Evidence indicated that inter-strain
      variability in conjugative metabolite formation of TCE might affect
      susceptibility to adverse health effects and that this method might aid in
      filling data gaps in human health assessment of TCE.

PMID- 29190189
TI  - Changes in working memory performance in youth following concussion.
AB  - OBJECTIVE: The purpose of this study was to compare the working memory (WM)
      performance pre- and post-concussion, and investigate the relationships between
      performance changes and characteristics such as self-reported symptom scores,
      number of days post-injury and age at injury in 10-14-year-old youth. METHODS:
      Twenty-one youth (17 males) aged 10-14 years recruited from the community
      completed verbal and non-verbal WM tasks pre- and post-concussion. Performance
      was measured using accuracy and performance errors (false alarms and misses). Pre
      and post-tests were compared using a Wilcoxon signed rank test, and effect size
      was determined using matched-pairs rank biserial correlation. RESULTS:
      Comparisons showed lower verbal WM accuracy at post-test, greater verbal and non
      verbal WM false alarm errors at post-test, and greater verbal WM miss errors at
      post-test (all r >= 0.30). Correlations between performance and characteristics
      revealed associations between younger youth and lower non-verbal WM accuracy and
      more false alarms at post-test, as well as an association among non-verbal WM
      miss errors, higher PCS scores and fewer days since injury at post-test.
      CONCLUSIONS: The current study found lower WM performance in youth following
      concussion. Furthermore, the findings suggest that false alarm errors may be a
      useful screening measure acutely post-concussion when assessing WM performance in
      youth.

PMID- 29190188
TI  - Biomeasures and mechanistic modeling highlight PK/PD risks for a monoclonal
      antibody targeting Fn14 in kidney disease.
AB  - Discovery of the upregulation of fibroblast growth factor-inducible-14 (Fn14)
      receptor following tissue injury has prompted investigation into biotherapeutic
      targeting of the Fn14 receptor for the treatment of conditions such as chronic
      kidney diseases. In the development of monoclonal antibody (mAb) therapeutics,
      there is an increasing trend to use biomeasures combined with mechanistic
      pharmacokinetic/pharmacodynamic (PK/PD) modeling to enable decision making in
      early discovery. With the aim of guiding preclinical efforts on designing an
      antibody with optimized properties, we developed a mechanistic site-of-action
      (SoA) PK/PD model for human application. This model incorporates experimental
      biomeasures, including concentration of soluble Fn14 (sFn14) in human plasma and
      membrane Fn14 (mFn14) in human kidney tissue, and turnover rate of human sFn14.
      Pulse-chase studies using stable isotope-labeled amino acids and mass
      spectrometry indicated the sFn14 half-life to be approximately 5 hours in healthy
      volunteers. The biomeasures (concentration, turnover) of sFn14 in plasma reveals
      a significant hurdle in designing an antibody against Fn14 with desired
      characteristics. The projected dose (>1 mg/kg/wk for 90% target coverage) derived
      from the human PK/PD model revealed potential high and frequent dosing
      requirements under certain conditions. The PK/PD model suggested a unique bell
      shaped relationship between target coverage and antibody affinity for anti-Fn14
      mAb, which could be applied to direct the antibody engineering towards an
      optimized affinity. This investigation highlighted potential applications,
      including assessment of PK/PD risks during early target validation, human dose
      prediction and drug candidate optimization.

PMID- 29190190
TI  - Letters to the Editor.

PMID- 29190191
TI  - Systemic manifestations of Cuterebra infection in dogs and cats: 42 cases (2000
      2014).
AB  - OBJECTIVE To document clinical signs in cats and dogs with Cuterebra infection,
      determine the outcome of infected animals, and determine whether Yorkshire
      Terriers were more commonly affected than other breeds of dogs. DESIGN
      Retrospective case series. ANIMALS 22 cats and 20 dogs with Cuterebra infection.
      PROCEDURES Medical records of dogs and cats with Cuterebra infection were
      reviewed for signalment, history, clinical and laboratory findings, treatment,
      duration of hospitalization, and outcome. RESULTS Most (16/20 [80%]) of the dogs
      weighed <= 4.5 kg (10 lb), and Yorkshire Terriers were overrepresented (8/20
      [40%]), compared with dogs of other breeds. Ten (50%) dogs and 3 (14%) cats had
      systemic inflammatory response syndrome at the time of initial evaluation, and 8
      (40%) dogs but none of the cats had disseminated intravascular coagulation. The
      overall mortality rate was 17% (7/42), but was higher for dogs (6/20 [30%]) than
      cats (1/22 [4.5%]). All 6 dogs that died weighed <= 4.5 kg and had systemic
      inflammatory response syndrome, disseminated intravascular coagulation, or both.
      CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that Cuterebra infection can
      cause severe systemic illness in small-breed dogs. Yorkshire Terriers were more
      commonly affected than were dogs of other breeds and, subjectively at least,
      appeared to be more likely to develop severe systemic illness.

PMID- 29190192
TI  - Suspected zonisamide-related anticonvulsant hypersensitivity syndrome in a cat.
AB  - CASE DESCRIPTION A 2-year-old neutered male domestic shorthair cat was evaluated
      for sudden onset of cluster seizures. CLINICAL FINDINGS At an emergency clinic,
      the cat had hyperimmunoglobulinemia and thrombocytopenia. On referral, treatment
      with levetiracetam, zonisamide, and phenobarbital initially provided good control
      of cluster seizure activity (attributable to epilepsy of unknow origin). Two
      weeks later, assessments revealed that serum phenobarbital concentration was
      within the ideal range but serum zonisamide concentration exceeded the
      recommended therapeutic range. The dosage of zonisamide was therefore decreased.
      Four days after dosage reduction, the cat developed generalized lymphadenopathy.
      Cytologic analysis of lymph node aspirate samples revealed a heterogeneous
      population of well-differentiated lymphocytes, interpreted as marked reactivity.
      Although neoplasia could not be ruled out, hypersensitivity to phenobarbital was
      suspected, and this treatment was discontinued. TREATMENT AND OUTCOME Despite
      cessation of phenobarbital administration, generalized peripheral lymphadenopathy
      progressed and hyperglobulinemia and cytopenias developed. These abnormalities
      resolved after discontinuation of zonisamide administration. The cat remained
      seizure free with no recurrence of the aforementioned concerns after
      reinstitution of phenobarbital treatment. CLINICAL RELEVANCE To the authors'
      knowledge, this is the first reported case of zonisamide-related lymphadenopathy,
      hyperglobulinemia, and cytopenias in a cat. Anticonvulsant hypersensitivity
      syndrome is well documented in human medicine, but little information has been
      published in the veterinary medical literature. Although the effects of
      anticonvulsant hypersensitivity syndrome in this cat were serious, these effects
      were reversible with treatment discontinuation.

PMID- 29190194
TI  - What Is Your Diagnosis?

PMID- 29190193
TI  - Characterization and comparison of injuries caused by spontaneous versus
      organized dogfighting.
AB  - OBJECTIVE To characterize and compare injuries found in dogs involved in
      spontaneously occurring dogfights with those of dogs used in illegal organized
      dogfighting. DESIGN Retrospective case-control study. ANIMALS 36 medium-sized
      dogs evaluated following spontaneous fights with a dog of the same sex and
      similar weight (medium dog-medium dog [MDMD] fights), 160 small dogs examined
      following spontaneous fights with a larger dog (big dog-little dog [BDLD]
      fights), and 62 dogs evaluated after being seized in connection with dogfighting
      law enforcement raids. PROCEDURES Demographic characteristics and injuries were
      recorded from medical records. Prevalence of soft tissue injuries in
      predetermined body surface zones, as well as dental or skeletal injuries, was
      determined for dogs grouped by involvement in BDLD, MDMD, and organized
      dogfights. The extent of injuries in each location was scored and compared among
      groups by 1-factor ANOVA. Patterns of injuries commonly incurred by each group
      were determined by use of prevalence data. RESULTS Mean extent of injury scores
      differed significantly among groups for all body surface zones except the eye and
      periorbital region. Mean scores for dental injuries and rib fractures also
      differed significantly among groups. Organized fighting dogs more commonly had
      multiple injuries, particularly of the thoracic limbs, dorsal and lateral aspects
      of the head and muzzle or oral mucosa, dorsal and lateral aspects of the neck,
      and ventral neck and thoracic region. CONCLUSIONS AND CLINICAL RELEVANCE To the
      authors' knowledge, this was the first study to compare injuries incurred during
      spontaneous and organized dogfighting. Establishing evidence-based patterns of
      injury will help clinicians identify dogs injured by organized dogfighting and
      aid in the prosecution of this crime.

PMID- 29190195
TI  - Puppy socialization practices of a sample of dog owners from across Canada and
      the United States.
AB  - OBJECTIVE To identify actions taken by owners to socialize puppies < 20 weeks of
      age, to determine factors affecting attendance of structured puppy classes, and
      to examine associations between class attendance and owner response to various
      undesirable puppy behaviors. DESIGN Cross-sectional study. SAMPLE 296 puppy
      owners (each with 1 puppy). PROCEDURES Participants completed a survey at
      enrollment (to gather data regarding owner demographics and puppy
      characteristics) and again when puppies were 20 weeks of age (to gather
      information on socialization practices and owner responses to misbehavior and
      signs of fear in their puppy). Responses were compared between owners that did
      (attendees) and did not (nonattendees) report attending puppy classes. RESULTS
      145 (49.0%) respondents reported attending puppy classes. Class structure
      differed greatly among respondents. Attendees exposed their puppies to a greater
      number of people and other dogs than nonattendees as well as to various noises
      and situations. Puppies of attendees were less likely than puppies of
      nonattendees to have signs of fear in response to noises such as thunder and
      vacuum cleaners as well as to crates. Fewer attendees reported use of punishment
      based discipline techniques than did nonattendees. Almost one-third of puppies
      received only minimal exposure to people and dogs outside the home during the
      survey period. CONCLUSIONS AND CLINICAL RELEVANCE A notable number of puppies <
      20 weeks of age in this study received few early socialization opportunities,
      which could lead to behavior problems and subsequent relinquishment.
      Opportunities exist for veterinarians to serve an important role in educating
      puppy owners about the importance of early puppy socialization and positive
      reward training.

PMID- 29190196
TI  - Clinical and histologic features of acute-onset erythroderma in dogs with
      gastrointestinal disease: 18 cases (2005-2015).
AB  - OBJECTIVE To describe the clinical and histologic features of acute erythroderma
      in dogs with gastrointestinal disease. DESIGN Retrospective case series. ANIMALS
      18 dogs with erythroderma and gastrointestinal disease. PROCEDURES Medical
      records and biopsy specimens were reviewed. Information collected from medical
      records included signalment, clinical signs, physical examination and diagnostic
      test results, treatment, and outcome. The Naranjo algorithm was used to estimate
      the probability of an adverse drug reaction for each dog. RESULTS All dogs had an
      acute onset of erythematous macules or generalized erythroderma. Histologic
      features of skin biopsy specimens had 3 patterns representing a progressive
      spectrum of inflammation. Most dogs had vomiting (n = 17) and hematochezia (10).
      Signs of gastrointestinal disease became evident before, after, or concurrent
      with the onset of skin lesions in 10, 3, and 5 dogs, respectively. Inflammatory
      bowel disease, pancreatitis, and adverse food reaction were diagnosed in 5, 3,
      and 3 dogs, respectively. The cause of the gastrointestinal signs was not
      identified for 8 dogs. Eight dogs had a Naranjo score consistent with a possible
      adverse drug reaction. Treatment of skin lesions included drug withdrawal (n =
      15), antihistamines (16), and corticosteroids (14). Signs of gastrointestinal
      disease and skin lesions resolved at a mean of 4.6 days and 20.8 days,
      respectively, after onset. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated
      acute erythroderma may be associated with > 1 gastrointestinal disease or an
      adverse drug reaction in some dogs. Recognition of the clinical and histologic
      features of this syndrome is essential for accurate diagnosis.

PMID- 29190197
TI  - Psychometric properties of the Canine Symptom Assessment Scale, a
      multidimensional owner-reported questionnaire instrument for assessment of
      physical symptoms in dogs with solid tumors.
AB  - OBJECTIVE To describe development and initial psychometric testing of the Canine
      Symptom Assessment Scale (CSAS), a multidimensional owner-reported questionnaire
      instrument, in a population of dogs with solid tumors enrolled in clinical
      trials. DESIGN Questionnaire development and validation study. ANIMALS 238 client
      owned dogs with solid tumors. PROCEDURES A 14-symptom questionnaire was
      developed. Symptoms were defined as subjective physical disturbances dogs
      experienced during the course of daily living as assessed through proxy reports
      of pet owners. For each symptom, owners reported frequency and severity of the
      symptom and extent of distress caused by the symptom for the dog and the owner.
      Questionnaire content, symptom prevalence and dimensionality, internal
      consistency, and factor structure were examined. Construct and criterion validity
      were examined via comparison with the Canine Brief Pain Inventory (CBPI). RESULTS
      Symptom prevalence was high, with pain and lack of energy reported in most dogs.
      Severity, versus frequency, was most highly correlated with both dog and owner
      distress. Two symptoms were removed from consideration because of poor
      performance. Analysis of the remaining 12 symptoms revealed that they could be
      grouped into 3 factors: malaise, anxiety, and digestive upset. The CSAS factor
      and total scores demonstrated predictable relationships with quality of life and
      pain scores as measured by the CBPI, including a significant association between
      increasing symptom burden and decreasing quality of life. The Cronbach alpha for
      the CSAS was 0.77. CONCLUSIONS AND CLINICAL RELEVANCE The 12-item CSAS was a
      psychometrically sound owner-reported instrument for assessment of symptom
      frequency and characteristics in client-owned dogs with solid tumors. Potential
      applications include clinical research and practice settings.

PMID- 29190198
TI  - Pathology in Practice.

PMID- 29190199
TI  - ECG of the Month.

PMID- 29190202
TI  - Lung lobe torsion in seven juvenile dogs.
AB  - CASE DESCRIPTION 7 juvenile (< 12 months old) dogs with lung lobe torsion were
      evaluated. CLINICAL FINDINGS All patients were male; breeds included Pug (n = 5),
      Chinese Shar-Pei (1), and Bullmastiff (1). Dyspnea and lethargy were the most
      common initial complaints, with a duration of clinical signs ranging from 1 to 10
      days. A CBC showed leukocytosis and neutrophilia in all dogs. Anemia was present
      in 6 dogs, 2 of which received packed RBC transfusions. The diagnosis was made on
      the basis of results of thoracic radiography, CT, ultrasonography, or a
      combination of modalities. The left cranial lung lobe was most commonly affected
      (n = 4), followed by the right middle lung lobe (2) and the right cranial lung
      lobe (1). TREATMENT AND OUTCOME A lateral intercostal thoracotomy with lobectomy
      of the affected lobe was performed in all patients. All dogs survived to be
      discharged between 1 and 2 days postoperatively. Six of 7 owners contacted for
      follow-up information 7 to 170 months after discharge reported satisfaction with
      the treatment and no apparent signs of recurrence of disease. CLINICAL RELEVANCE
      The juvenile patients of this report were successfully treated surgically with no
      apparent complications. Clinicians should be aware of the possibility of lung
      lobe torsion when evaluating young dogs with clinical signs related to the
      respiratory system, including those with vague signs, to avoid undue delays in
      treatment.

PMID- 29190204
TI  - Pathology in Practice.

PMID- 29190205
TI  - Hypertension regulating angiotensin peptides in the pathobiology of
      cardiovascular disease.
AB  - Renin angiotensin system (RAS) is an endogenous hormone system involved in the
      control of blood pressure and fluid volume. Dysregulation of RAS has a
      pathological role in causing cardiovascular diseases through hypertension. Among
      several key components of RAS, angiotensin peptides, varying in amino acid length
      and biological function, have important roles in preventing or promoting
      hypertension, cardiovascular diseases, stroke, vascular remodeling etc. These
      peptides are generated by the metabolism of inactive angiotensinogen or its
      derived peptides by hydrolyzing action of certain enzymes. Angiotensin II,
      angiotensin (1-12), angiotensin A and angiotensin III bind primarily to
      angiotensin II type 1 receptor and cause vasoconstriction, accumulation of
      inflammatory markers to sub-endothelial region of blood vessels and activate
      smooth muscle cell proliferation. Moreover, when bound to angiotensin II type 2
      receptor, angiotensin II works as cardio-protective peptide and halt pathological
      cell signals. Other peptides like angiotensin (1-9), angiotensin (1-7),
      alamandine and angiotensin IV also help in protecting from cardiovascular
      diseases by binding to their respective receptors.

PMID- 29190206
TI  - Housing, citizenship, and communities for people with serious mental illness.

PMID- 29190209
TI  - National Study of Burnout and Career Satisfaction Among Physician Assistants in
      Oncology: Implications for Team-Based Care.
AB  - PURPOSE: A high rate of burnout has been reported in oncology physicians.
      Physician assistants (PAs) may also face similar risks of burnout. We sought to
      measure the personal and professional characteristics associated with burnout and
      career satisfaction and the potential impact on the oncology PA workforce.
      PARTICIPANTS AND METHODS: A national survey of PAs in oncology was completed by
      using the Maslach Burnout Inventory from September 2015 to January 2016. RESULTS:
      In all, 855 PAs were contacted and 250 submitted complete surveys (response rate,
      29.2%). Respondents were representative of PAs in oncology with a mean age of
      41.8 years, females (88.8%), academic practice (55.2%), urban location (61.2%),
      outpatient (74.4%), medical oncology (75.2%), worked 41 to 50 hours per week
      (52.8%), and had a mean of 9.6 years as a PA in oncology. Burnout was reported in
      34.8% of PAs, 30.4% reported high emotional exhaustion, 17.6% reported high
      depersonalization, and 19.6% reported a low sense of personal accomplishment. In
      multivariable analysis, age, time spent on indirect patient care, oncology
      subspecialty, and relationship with collaborating physician were factors
      associated with burnout. Career and specialty satisfaction was high (86.4% and
      88.8%, respectively). In the next 2 years, only 3.6% of PAs plan to pursue a
      different career or specialty and only 2.0% plan to retire. CONCLUSION: Despite
      high career and specialty satisfaction, burnout is reported in one third of PAs
      in oncology. Further exploration of the relationship between PAs and
      collaborating physicians may provide insight on methods to decrease burnout.
      Negligible short-term attrition of the current oncology PA workforce is
      anticipated.

PMID- 29190210
TI  - Ceftriaxone-Resistant Neisseria gonorrhoeae, Canada, 2017.

PMID- 29190211
TI  - Identification and management of familial breast cancer in Austria.
AB  - Aim The aim of this study is to review the legal implications, the technology,
      the indications and the management of women with a familial background of breast
      and/or ovarian cancer. Methods We have reviewed the literature and national
      Austrian guidelines to describe the uptake of genetic counseling and the
      management options offered in Austria. Results Genetic testing for the BRCA1 and
      2 mutations is free and readily available through a nation-wide program.
      Increased awareness and the availability of screening programs and prophylactic
      surgery have resulted in a profound increase in genetic counseling and testing in
      women with a familial background of breast and ovarian cancer in Austria.
      Conclusion While readily available country-wide counseling has led to an increase
      in counseling and testing, Austrian legislation mandates "non-directional
      counseling" resulting in a comparatively low uptake of prophylactic surgery.

PMID- 29190212
TI  - Knowledge, attitude and practice towards eating and physical activity among
      primary school children in Brunei: a cross-sectional study.
AB  - Background Childhood obesity has become a global public health crisis. Many
      studies have been conducted to explore the knowledge, attitude and practices
      towards eating and physical activity amongst parents and healthcare workers.
      However, very little is known amongst children. It is imperative to understand
      these factors as they have been associated with obesity among children. Objective
      This study aimed to assess the knowledge, attitude and practices of Bruneian
      children towards eating and physical activity, in order to identify the factors
      that influence the development of obesity. Methods The study involved 353
      children from four primary schools in Brunei. The data collection tool used was
      modified validated questionnaires with sections on demographic characteristic,
      knowledge about obesity, eating habits and physical activity. Results The
      majority of children (>60%) had good knowledge of obesity and intake of healthy
      food, but, 84.2% lacked knowledge on the required daily servings of fruits and
      vegetables. 68.8% purchased food and beverages from their school canteen. 93.8%
      were aware about the health benefits of physical activity and 70.2% spent only 1
      2 h of screen time per day, however, 46.9% did not meet the recommended amount of
      physical activity although they reported to have performed enough. This suggested
      that a comprehensive education on food intake requirements and physical activity
      are necessary in order to better educate children. Conclusion Health educators
      and public health professionals may find our findings useful in order to plan and
      develop tailored interventions for children, as well as better promotion of a
      healthy lifestyle to children and their families.

PMID- 29190213
TI  - The Transition from Military Nurse to Nurse Faculty: A Descriptive Study.
AB  - Aim The aim of this qualitative descriptive study was to describe the transition
      from military nurse to nurse faculty. Background There is a global shortage of
      qualified nurse faculty. Recruitment of retiring or separating military nurses is
      a viable solution. Methods Content and thematic analysis of semi-structured
      interviews of former military nurses (N=13) was undertaken. Results The
      transition from military nurse to nurse faculty includes acknowledgment of the
      reality of academic culture, appreciation of the journey to bridge the gap, and
      culmination of a new identity. Leadership skills acquired during military service
      proved instrumental to a successful transition. Conclusions Recognizing this
      transition and the strengths these nurses offer provides evidence for focused
      orientation programs to increase recruitment and retention of these faculty.

PMID- 29190214
TI  - Anti-telomerase T cells adoptive transfer.

PMID- 29190215
TI  - Can oxygen anosmia extend lifespan?

PMID- 29190216
TI  - Networked concave microwell arrays for constructing 3D cell spheroids.
AB  - The engineered three-dimensional (3D) cell cultivation system for the production
      of multicellular spheroids has attracted considerable attention due to its
      improved in vivo relevance to cellular communications compared with the
      traditional two-dimensional (2D) cell culture platform. The formation and
      maintenance of cell spheroids in a healthy condition is the critical factor for
      tissue engineering applications such as the repair of damaged tissues, the
      development of organ replacement parts and preclinical drug tests. However,
      culturing spheroids in conventional isolated single wells shows limited yield and
      reduced maintenance periods due to the lack of proper supplies of nutrition as
      well as intercellular chemical signaling. Here, we develop novel networked
      concave microwell arrays for the effective construction of 3D multi-cellular
      spheroids. The proposed method provides a suitable structure for the diffusion of
      oxygen, water-soluble nutrients and cytokines for cell-cell interactions between
      the spheroids in neighboring microwells. We have further demonstrated that
      hepatocyte spheroid cultured networked concave microwells show enhanced cell
      viability and albumin secretion compared to the un-networked control group over
      two weeks. Our results reveal that multi-cellular functionality can be tuned up
      by networking individual 3D spheroids without supplying additional chemicals or
      biological supplements. We anticipate our result to be useful in high-throughput
      cellular screening platforms to study cell-cell interactions, in response to
      diverse chemical stimuli as well as the development of the in vivo mimicking of
      the customized 3D tissue culture system.

PMID- 29190217
TI  - The Role of Histopathology and Immunohistochemistry in the Diagnosis of Cutaneous
      Leishmaniasis Without "Discernible" Leishman-Donovan Bodies.
AB  - BACKGROUND: Histopathology plays an important role in the diagnosis of cutaneous
      leishmaniasis (CL) but Leishman-Donovan (LD) bodies may not always be
      discernible. Recently, anti-CD1a antibody (Ab), clone MTB1, was found to decorate
      LD bodies immunohistochemically. OBJECTIVE: Can histopathology without
      discernible LD bodies be used to diagnose CL, and can immunohistochemistry using
      anti-CD1a Ab, clone MTB1, detect LD bodies in these cases. METHODS: Suspected CL
      lesions were studied histopathologically and immunohistochemically, and the
      patients' clinical files were reviewed. RESULTS: Of the 196 patients with
      suspected CL, direct smear demonstrated LD bodies in 50 (25.5%). Of the remaining
      146 patients, 118 underwent biopsy. In 56 (47.5%) patients, the hematoxylin-eosin
      stained sections revealed LD bodies. In 47 (39.8%) patients, LD bodies were not
      discerned but the histopathology demonstrated histiocytic infiltrates with
      varying numbers of plasma cells along with other inflammatory cells, and negative
      Ziehl-Neelsen and periodic acid-Schiff stains. This pattern was termed
      "histopathology consistent with leishmaniasis." The history, clinical findings,
      and response to anti-leishmania therapy supported the diagnosis of CL in all of
      them, and immunostains for CD1a, clone MTB1, detected LD bodies in 11 (23.4%) of
      these 47 patients. CONCLUSIONS: "Histopathology consistent with CL" along with
      appropriate clinical findings supports the diagnosis of CL in an endemic area,
      and immunostains with CD1a Ab, clone MTB1, may help in the minority of the cases.

PMID- 29190218
TI  - Validation of a Real-Time Minute-to-Minute Urine Output Monitor and the
      Feasibility of Its Clinical Use for Patients Undergoing Cardiac Surgery.
AB  - Acute kidney injury after cardiac surgery is associated with increased morbidity
      and mortality. Methods for measuring urine output in real time may better ensure
      renal perfusion perioperatively in contrast to the current standard of care where
      urine output is visually estimated after empiric epochs of time. In this study,
      we describe an accurate method for monitoring urine output continuously during
      cardiopulmonary bypass. This may provide a means for setting patient-specific
      targets for blood pressure and cardiopulmonary bypass flow as a potential
      strategy to reduce the risk for acute kidney injury.

PMID- 29190219
TI  - Enhanced Recovery After Surgery: Current Controversies and Concerns.

PMID- 29190221
TI  - The Analgesic Effects of (5R,6R)6-(3-Propylthio-1,2,5-thiadiazol-4-yl)-1
      azabicyclo[3.2.1] Octane on a Mouse Model of Neuropathic Pain: Erratum.

PMID- 29190220
TI  - Socioeconomic Deprivation and Utilization of Anesthetic Care During Pregnancy and
      Delivery: A French Retrospective, Multicenter, Cohort Study: Erratum.

PMID- 29190222
TI  - Platelet Counts and Postoperative Stroke After Coronary Artery Bypass Grafting
      Surgery: Erratum.

PMID- 29190223
TI  - Electroconvulsive Therapy: A Time for Networks.

PMID- 29190224
TI  - Electroconvulsive Therapy and Delirious Catatonic Mania.

PMID- 29190225
TI  - Varied Antidepressant Response and Subjective Experience Across 3 Different
      Repetitive Transcranial Magnetic Stimulation Devices: A Case Report.

PMID- 29190226
TI  - Time Course of Changes in Neuromuscular Parameters During Sustained Isometric
      Muscle Actions: Erratum.

PMID- 29190227
TI  - Potential of Noncontrast Magnetic Resonance Imaging With Diffusion-Weighted
      Imaging in Characterization of Breast Lesions: Intraindividual Comparison With
      Dynamic Contrast-Enhanced Magnetic Resonance Imaging.
AB  - OBJECTIVES: The aim of this study was to assess the potential of noncontrast
      magnetic resonance imaging (NC-MRI) with diffusion-weighted imaging (DWI) in
      characterization of breast lesions in comparison to dynamic contrast-enhanced MRI
      (DCE-MRI) at 3 T. MATERIALS AND METHODS: Consecutive patients with conventional
      imaging (mammography, ultrasound) BI-RADS 4/5 findings were included in this
      institutional review board-approved single-center study. All underwent 3 T breast
      MRI including readout-segmented DWI, DCE, and T2-weighted sequences. Final
      diagnosis was defined by histopathology or follow-up (>24 months). Two
      experienced radiologists (R1, R2) independently assigned lesion conspicuity (0 =
      minimal to 3 = excellent) and BI-RADS scores to NC-MRI (readout-segmented DWI
      including apparent diffusion coefficient maps) and DCE-MRI (DCE and T2-weighted).
      Receiver operating characteristics, kappa statistics, and visual grading
      characteristics analysis were applied. RESULTS: Sixty-seven malignant and 56
      benign lesions were identified in 113 patients (mean age, 54 +/- 14 years). Areas
      under the receiver operating characteristics curves were similar: DCE-MRI: 0.901
      (R1), 0.905 (R2); NC-MRI: 0.882 (R1), 0.854 (R2); P > 0.05, respectively. The
      kappa agreement was 0.968 (DCE-MRI) and 0.893 (NC-MRI). Visual grading
      characteristics analysis revealed superior lesion conspicuity by DCE-MRI (0.661,
      P < 0.001). CONCLUSIONS: Diagnostic performance and interreader agreement of both
      NC-MRI and DCE-MRI is high, indicating a potential use of NC-MRI as an
      alternative to DCE-MRI. However, inferior lesion conspicuity and lower
      interreader agreement of NC-MRI need to be considered.

PMID- 29190228
TI  - Hepatic Venous Outflow Stenosis After Auxiliary Left Hemiliver Transplantation
      Diagnosed by Ultrasonic Shear Wave Elastography Combined With Doppler
      Ultrasonography.
AB  - Hepatic vein stenosis after liver transplantation is a relatively rare
      complication that could even result in graft loss. However, it is difficult to
      arrive at a definite diagnosis at the early stage of postoperation, and there are
      few researches on ultrasonic shear wave elastography in the diagnosis of hepatic
      vein stenosis. We report the case of an 11-year-old male patient with cirrhosis
      due to hepatolenticular degeneration who received an auxiliary left hemiliver
      graft from his uncle. Massive ascites developed in 4 days after the operation.
      Stenosis was suspected at the site of anastomosis by Doppler ultrasonography when
      elevating the velocity of the left hepatic vein. Meanwhile, increased stiffness
      of the graft was revealed by ultrasonic shear wave elastography. The stenosis was
      confirmed by subsequent digital subtraction angiography. Ascites decreased
      gradually after the stent implantation. Our case indicates that ultrasonic shear
      wave elastography combined with Doppler ultrasonography is a promising method for
      noninvasive diagnosis of hepatic venous outflow stenosis following liver
      transplantation.

PMID- 29190229
TI  - CORRELATION BETWEEN OUTER RETINAL THICKENING AND RETINAL FUNCTION IMPAIRMENT IN
      PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANES.
AB  - PURPOSE: To examine the relationship between retinal layer thickness, retinal
      sensitivity, and visual function in patients with idiopathic epiretinal membrane
      using spectral domain optical coherence tomography automated segmentation
      algorithm. METHODS: Twenty-four eyes with epiretinal membrane and 12 control eyes
      were enrolled. Ophthalmic evaluations included best-corrected visual acuity, mean
      retinal sensitivity (MRS) of radial 10 degrees  and 4 degrees  areas tested with
      microperimetry, and measurements of 4 retinal layer thicknesses by means spectral
      domain optical coherence tomography. Relations between retinal layer thickness,
      MRS, and best-corrected visual acuity values were explored. RESULTS: Compared
      with controls, MRS (P < 0.001) and best-corrected visual acuity (P < 0.001)
      values were reduced. In the epiretinal membrane group, MRS of the central 4
      degrees  values was associated with thickening of the outer nuclear layer (P <
      0.05). Furthermore, a correlation was found between the inner nuclear layer
      thickening and the MRS of the central 4 degrees  limited to the inferior quadrant
      (P < 0.05). The decreased best-corrected visual acuity values were correlated
      with the thickening of three of four quadrant of the inner nuclear layer,
      inferior and temporal quadrants of the outer plexiform layer, and finally outer
      nuclear layer nasal quadrant. CONCLUSION: We found a meaningful correlation
      between MRS impairment of the central 4 degrees  and outer nuclear layer
      thickness and showed which intraretinal layers mainly contributes to visual
      acuity loss.

PMID- 29190230
TI  - Ocular Neovascularization in Endogenous Candida Endophthalmitis: Using Multimodal
      Imaging to Understand Different Pathogenic Pathways.

PMID- 29190231
TI  - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE FOVEAL AVASCULAR ZONE IN CHILDREN
      WITH A HISTORY OF TREATMENT-REQUIRING RETINOPATHY OF PREMATURITY.
AB  - PURPOSE: To examine the characteristics of the foveal vascular structure of
      patients with retinopathy of prematurity (ROP) by optical coherence tomography
      angiography. METHODS: Ten patients with a history of laser photocoagulation or
      cryopexy treatment for Stage 3 (Zone >= II) ROP and 10 normal subjects (controls)
      were included. Foveal avascular zone, vessel density, vessel length, and vascular
      diameter index were measured by optical coherence tomography angiography using
      the 3 * 3-mm Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. RESULTS:
      The median foveal avascular zone values of the patients with ROP and controls
      were 0.103 mm and 0.260 mm, respectively (P = 0.0025). The medians of the vessel
      density, vessel length, and vascular diameter index of the patients with ROP were
      0.218 mm/mm, 11.75 mm/mm, and 18.00 MUm, respectively, in ETDRS Sector 1 and did
      not significantly differ from those of the controls (P = 0.940, 0.733, and 0.705,
      respectively). For the average of ETDRS Sectors 2 to 5, the medians of the vessel
      density, vessel length, and vascular diameter index for the patients with ROP
      were 0.347 mm/mm, 18.95 mm/mm, and 18.28 MUm, respectively; vessel density and
      vessel length were significantly smaller than those of the controls (P = 0.002
      and 0.003, respectively), but there was no significant difference in vascular
      diameter index (P = 0.286). CONCLUSION: Optical coherence tomography angiography
      guided foveal avascular zone was significantly smaller in patients with ROP than
      in controls. Our results indicate that foveal vascular development may be altered
      in patients with a history of treatment-requiring ROP.

PMID- 29190232
TI  - MACULAR ATROPHY FINDINGS BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY COMPARED
      WITH FUNDUS AUTOFLUORESCENCE IN TREATED EXUDATIVE AGE-RELATED MACULAR
      DEGENERATION.
AB  - PURPOSE: To compare the areas of choriocapillaris (CC) nonperfusion and macular
      atrophy (MA) in treated exudative age-related macular degeneration. METHODS: This
      was a prospective, observational, cross-sectional study. Forty-four eyes
      exhibiting MA (42 patients with age-related macular degeneration), with a dry
      macula, underwent fundus autofluorescence and optical coherence tomography
      angiography. The area of MA detected by fundus autofluorescence and CC
      nonperfusion detected by optical coherence tomography angiography was measured
      using image analysis software. The rates of concordance between the MA and CC
      nonperfusion areas were calculated. We qualitatively and quantitatively compared
      the areas of MA and CC nonperfusion in age-related macular degeneration eyes.
      RESULTS: The mean areas of MA and CC nonperfusion were 5.95 +/- 4.50 mm and 10.66
      +/- 7.05 mm, respectively (paired t-test, P < 0.001). In 39 eyes (88.6%), the CC
      nonperfusion area was larger than the MA area, and the mean CC nonperfusion area
      was significantly larger than the mean MA area. Fundus autofluorescence matching
      optical coherence tomography angiography showed that the CC nonperfusion area was
      almost included in the MA area. The mean concordance rate for the MA area inside
      the CC nonperfusion area was 87.7 +/- 13.9%. CONCLUSION: The MA and CC
      nonperfusion areas markedly overlapped. The area of CC nonperfusion correlated
      with the MA area. Choroidal ischemia might be involved in the pathogenesis of MA
      in treated age-related macular degeneration.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.

PMID- 29190233
TI  - Correspondence.

PMID- 29190234
TI  - FAMILIAL CENTRAL SEROUS CHORIORETINOPATHY.
AB  - PURPOSE: To assess ophthalmologic characteristics in patients and unaffected
      individuals in families with multiple members affected by central serous
      chorioretinopathy (CSC), both at presentation and long-term follow-up. METHODS:
      In 103 subjects from 23 families with at least 2 affected patients with CSC per
      family, prospective extensive ophthalmologic examination was performed, including
      best-corrected visual acuity, indirect ophthalmoscopy, digital color fundus
      photography, optical coherence tomography, fundus autofluorescence, and
      fluorescein angiography imaging. From these, 24 individuals from 6 families had
      undergone extensive ophthalmologic examination in either 1994 or 1995 and were
      followed up in this study. RESULTS: Subretinal fluid accumulation on optical
      coherence tomography and/or "hot spots" of leakage on fluorescein angiography
      indicative of CSC were detected in 45 of 103 phenotyped subjects (44%). Findings
      suggestive of CSC, but without the presence of subretinal fluid on optical
      coherence tomography and/or "hot spots" of leakage on fluorescein angiography,
      were observed in an additional 27 family members (26%). In 4 of 17 previously
      nonaffected subjects (24%) from the 24 individuals that were followed up after
      more than 20 years, we found more severe abnormalities. CONCLUSION: Extensive
      ophthalmologic phenotyping resulted in the detection of (suggestive) CSC in 52%
      of family members of patients with CSC. Genetic factors may play an important
      role in these specific CSC cases. Moreover, during follow-up, progressive disease
      can occur in a noteworthy number of patients.

PMID- 29190235
TI  - Global Connections to Study Idiopathic Macular Telangiectasia Type 2.

PMID- 29190236
TI  - APOPTOSIS AND ANGIOFIBROSIS IN DIABETIC TRACTIONAL MEMBRANES AFTER VASCULAR
      ENDOTHELIAL GROWTH FACTOR INHIBITION: Results of a Prospective Trial. Report No.
      2.
AB  - PURPOSE: We sought to characterize the angiofibrotic and apoptotic effects of
      vascular endothelial growth factor (VEGF)-inhibition on fibrovascular epiretinal
      membranes in eyes with traction retinal detachment because of proliferative
      diabetic retinopathy. METHODS: Membranes were excised from 20 eyes of 19 patients
      (10 randomized to intravitreal bevacizumab, 10 controls) at vitrectomy. Membranes
      were stained with antibodies targeting connective tissue growth factor (CTGF) or
      VEGF and colabeled with antibodies directed against endothelial cells (CD31),
      myofibroblasts, or retinal pigment epithelium markers. Quantitative and
      colocalization analyses of antibody labeling were obtained through
      immunofluorescence confocal microscopy. Masson trichrome staining, cell counting
      of hematoxylin and eosin sections, and terminal dUTP nick-end labeling staining
      were performed. RESULTS: High levels of fibrosis were observed in both groups.
      Cell apoptosis was higher (P = 0.05) in bevacizumab-treated membranes compared
      with controls. The bevacizumab group had a nonsignificant reduction in
      colocalization in CD31-CTGF and cytokeratin-VEGF studies compared with controls.
      Vascular endothelial growth factor in extracted membranes was positively
      correlated with vitreous levels of VEGF; CTGF in extracted membranes was
      negatively correlated with vitreous levels of CTGF. CONCLUSION: Bevacizumab
      suppresses vitreous VEGF levels, but does not significantly alter VEGF or CTGF in
      diabetic membranes that may be explained by high baseline levels of fibrosis.
      Bevacizumab may cause apoptosis within fibrovascular membranes.

PMID- 29190237
TI  - IMPACT OF ETIOLOGY ON THE OUTCOME OF PEDIATRIC RHEGMATOGENOUS RETINAL DETACHMENT.
AB  - PURPOSE: To evaluate the clinical features and surgical outcomes of
      rhegmatogenous retinal detachment in pediatric patients and to identify the
      independent effect of each etiology on the outcome. METHODS: A review of patients
      younger than 18 years who underwent vitreoretinal surgery was conducted at Chang
      Gung Memorial Hospital, Taoyuan, between 2008 and 2013. Patients were classified
      according to etiology. Multivariate logistic regression analysis was performed to
      evaluate the association between outcomes and each etiologic factor. RESULTS: A
      total of 86 cases (mean age: 12.9 +/- 4.8 years; 76.7% male) were included. The
      mean follow-up was 46.3 +/- 23.9 months. In 90.7% of patients, at least one
      etiology could be identified, including myopia (55.8%), congenital or
      developmental disease (39.5%), trauma (27.9%), and previous intraocular surgery
      (17.4%). Among the risk factors examined in this study, congenital or
      developmental disease had the worst functional outcomes (P = 0.006). Myopia was a
      good prognostic factor for a better retinal reattachment rate (P = 0.030). Myopic
      rhegmatogenous retinal detachment had the lowest probability of surgical failure
      (8.08%), and idiopathic rhegmatogenous retinal detachment had the lowest
      likelihood of postoperative visual decline (4.65%). CONCLUSION: Myopia and
      congenital or developmental disease are the leading etiologies of pediatric
      rhegmatogenous retinal detachment. Different etiologies are associated with
      distinctive outcomes, and congenital and developmental diseases are independent
      prognostic factors of a poor response.

PMID- 29190239
TI  - Diagnostic and Therapeutic Challenges.

PMID- 29190238
TI  - LONGITUDINAL CHANGES IN THE OPTIC NERVE HEAD AND RETINA OVER TIME IN VERY YOUNG
      CHILDREN WITH FAMILIAL EXUDATIVE VITREORETINOPATHY.
AB  - PURPOSE: To explore vitreoretinal pathologies and their longitudinal changes
      visible on handheld optical coherence tomography (OCT) of young children with
      familial exudative vitreoretinopathy. METHODS: The authors retrospectively
      analyzed handheld OCT images for vitreoretinal interface and retinal
      abnormalities and optic nerve head (ONH) elevation. RESULTS: From 26 eyes of 16
      children (mean age 32 months) with familial exudative vitreoretinopathy, 10 had
      ONH dragging on photographs, and in these, handheld OCT revealed temporal and
      anterior retinal displacement, prominent vitreopapillary adhesion or traction,
      and retinal nerve fiber layer thickening at ONH margins with adjacent retinal
      elevation. Despite a nearly normal photographic appearance, handheld OCT revealed
      ONH elevation with vitreopapillary traction (6/16 eyes), ONH edema (1/16 eye),
      and retinal vascular protrusion (5/16 eyes). Handheld OCT-visualized vitreous
      abnormalities (18/26 eyes) were more prevalent at higher stages of disease.
      Handheld OCT-visualized elevation of ONH and the retina worsened over time in
      nine eyes and improved in 5/6 eyes after vitrectomy. CONCLUSION: Handheld OCT can
      detect early ONH, retinal, and vitreous changes in eyes with familial exudative
      vitreoretinopathy. Contraction of strongly adherent vitreous in young patients
      with familial exudative vitreoretinopathy appears to cause characteristic ONH
      dragging and tractional complications without partial posterior vitreous
      detachment. Vitreopapillary dragging may be visible only on OCT and may progress
      in the absence of obvious retinal change on conventional examination.

PMID- 29190240
TI  - COMPARING MICROPERIMETRIC AND STRUCTURAL FINDINGS IN PATIENTS WITH BRANCH RETINAL
      VEIN OCCLUSION AND DIABETIC MACULAR EDEMA.
AB  - PURPOSE: To compare retinal sensitivity and central retinal thickness in patients
      with focal diabetic macular edema (DME) and edema secondary to branch retinal
      vein occlusion (BRVO). METHODS: In this consecutive, cross-sectional,
      observational study, patients with either DME or BRVO underwent measurements for
      best-corrected visual acuity, microperimetry, and spectral domain optical
      coherence tomography. Retinal thickness and sensitivity were measured using Optos
      Spectral optical coherence tomography/scanning laser ophthalmoscopy (Optos plc,
      Dunfermline, Scotland, United Kingdom). Areas defined as abnormal demonstrated
      edema with clearly defined cystic spaces. Abnormal and control areas were
      compared in mean retinal sensitivity and mean retinal thickness for both
      conditions. RESULTS: Twenty eyes with focal DME and nine eyes with BRVO were
      included. In DME, mean retinal thickness was 413.6 +/- 84.5 MUm and 291.7 +/-
      36.7 MUm in abnormal and control areas, respectively. Mean retinal sensitivity
      was 10.22 +/- 4.23 dB and 12.25 +/- 3.57 dB, respectively. In BRVO, mean retinal
      thickness was 491.4 +/- 102.9 MUm and 315.9 +/- 29.9 MUm in abnormal and control
      areas, respectively. Mean retinal sensitivity was 6.36 +/- 5.47 dB and 13.05 +/-
      2.28 dB. In DME, a decrease in retinal thickness of 0.341 MUm correlated with 1
      dB reduction of retinal sensitivity, although this was not statistically
      significant (P = 0.717). In BRVO, however, an increase in retinal thickness of
      9.702 MUm correlated with 1 dB reduction of retinal sensitivity (P = 0.001).
      CONCLUSION: In BRVO, an increase in retinal thickness corresponded with a
      significant reduction in retinal sensitivity; in DME, however, there was no
      significant correlation between retinal thickness and retinal sensitivity.
      Further study is required to assess why this is the case. The Optos Spectral
      optical coherence tomography/scanning laser ophthalmoscopy allows for a reliable
      point-to-point correlation, as microperimetry and spectral domain optical
      coherence tomography can be performed in the same device.

PMID- 29190241
TI  - AFLIBERCEPT AFTER RANIBIZUMAB INTRAVITREAL INJECTIONS IN EXUDATIVE AGE-RELATED
      MACULAR DEGENERATION: The ARI2 Study.
AB  - PURPOSE: To analyze the efficacy of aflibercept switch treatment for regression
      of pigment epithelial detachment (PED) in patients previously treated with
      ranibizumab. METHODS: Multicenter, prospective, nonrandomized clinical trial. One
      eye of patients presenting neovascular age-related macular degeneration with PED
      of more than 250 MUm in height, with persistent fluid, was included. Patients had
      to have received at least six ranibizumab intravitreal injections during the 12
      months before enrollment. Patients were switched from ranibizumab pro re nata to
      aflibercept (fixed regimen, 3 monthly intravitreal injections, and then Q6). Main
      outcome measure was change in PED height from baseline to Week 12 after switch.
      Secondary outcomes were best-corrected visual acuity and PED volume changes.
      RESULTS: Eighty four patients were included. Mean delay between last ranibizumab
      intravitreal injection and switch was 44.7 days. Mean maximal PED height at
      baseline visit was 347 MUm (+/-109) and reduced to a mean of 266 MUm (+/-114) at
      Week 12 (P < 0.001) and 288.2 MUm at Week 32 (P < 0.001). Mean PED volume was
      reduced from 1.3 mm to 0.98 mm at Week 12 (P < 0.001). Best-corrected visual
      acuity improved by 3.3 Early Treatment Diabetic Retinopathy Study letters at Week
      32 (P = 0.003). CONCLUSION: Aflibercept switch therapy seems to be effective on
      large PED in patients previously treated with pro re nata ranibizumab.

PMID- 29190242
TI  - A Viscoelastic Aspiration Technique for Autologous Transplantation of the Free
      Flap Inner Limiting Membrane During Macular Hole Surgery.

PMID- 29190243
TI  - FACTORS ASSOCIATED WITH SEROUS RETINAL DETACHMENT IN HIGHLY MYOPIC EYES WITH
      VERTICAL OVAL-SHAPED DOME.
AB  - PURPOSE: This study investigated factors associated with persistent serous
      retinal detachment in highly myopic eyes with vertical oval-shaped domes.
      METHODS: Twenty-eight highly myopic patients (40 eyes) with smooth macular
      elevations related to a vertical oval-shaped dome were recruited. Serous retinal
      detachment was investigated; 11 eyes had persistent submacular fluid (study
      group) and 29 eyes lacked submacular fluid (control group). All patients
      underwent complete ophthalmologic examinations, including axial-length
      measurement and fluorescein angiography. Spectral domain optical coherence
      tomography scans through the fovea measured choroidal thicknesses, macular bulge
      height, and vitreoretinal interface factors. RESULTS: No studied variables (age,
      sex, spherical equivalence, axial length, vitreomacular traction, epiretinal
      membrane, and internal limiting membrane detachment) except higher macular bulge
      height (P = 0.03) and a reduced macular choroidal thickness (P = 0.02) were
      associated with the risk of serous retinal detachment. No statistically
      significant differences in best-corrected visual acuity were observed between the
      study and control groups. Serous retinal detachment always occurred at the top of
      the inward incurvation of the macula and was characterized by multiple
      hyperfluorescent granular patches on fluorescein angiography. CONCLUSION: A
      higher macular bulge height and a reduced macular choroidal thickness might be
      important factors in the development of serous retinal detachment in patients
      with vertical oval-shaped domes.

PMID- 29190244
TI  - EVALUATION OF OBSTRUCTIVE SLEEP APNEA SYNDROME AS A RISK FACTOR FOR DIABETIC
      MACULAR EDEMA IN PATIENTS WITH TYPE II DIABETES.
AB  - PURPOSE: To evaluate the association between obstructive sleep apnea and diabetic
      macular edema (DME) in patients with Type II diabetes, using the apnea-hypopnea
      index and other nocturnal hypoxemia parameters. METHODS: This cross-sectional,
      case-control study included 99 patients with Type II diabetes: the first group
      included patients with DME (DME+ group) and the second patients without DME (DME-
      group). Polysomnography was performed in all patients. The two groups were
      compared, and the risk factors were studied using logistic regression. RESULTS:
      The DME+ group comprised 38 patients, and the DME- group comprised 61 patients,
      aged a mean 68.8 years and 66.3 years (P = 0.27), respectively; mean body mass
      index was 29.7 and 30.9 (P = 0.16), respectively. The mean apnea-hypopnea index
      was significantly higher in the DME+ group (43.95 [13.5-87.3]) than in the DME-
      group (35.18 [3.55-90.7]) (P = 0.034). Patients with DME had more severe
      obstructive sleep apnea (apnea-hypopnea index >30) than the others: 71% versus
      50.8% (P = 0.049). Cumulative time of SPO2 below 90% (CT90%) was independently
      associated with DME after adjusting for confounding factors, whereas there was no
      difference between the oxygen desaturation index and minimum O2 saturation.
      CONCLUSION: Severe obstructive sleep apnea (apnea-hypopnea index >30) and
      parameters of nocturnal hypoxemia (cumulative time of SPO2 below 90%) are
      associated with DME.

PMID- 29190245
TI  - CHARACTERIZATION AND CORRELATION OF "JAMPOL DOTS" ON ADAPTIVE OPTICS WITH FOVEAL
      GRANULARITY ON CONVENTIONAL FUNDUS IMAGING.
AB  - PURPOSE: To describe features characteristic of multiple evanescent white dot
      syndrome (MEWDS) using adaptive optics scanning laser ophthalmoscopy (AOSLO).
      METHODS: Six women (seven eyes) who presented with MEWDS between June 2014 and
      April 2017 underwent ophthalmologic examinations and multimodal imaging including
      infrared, AOSLO, and spectral domain optical coherence tomography. RESULTS:
      Bright hyperreflective lesions on AOSLO throughout the course of MEWDS could be
      correlated to the hyperreflective dots of foveal granularity on infrared imaging
      without apparent corresponding changes on spectral domain optical coherence
      tomography. During the acute phase of MEWDS, extrafoveal hyperreflective dots
      were also visible on AOSLO and infrared and were associated with accumulations of
      hyperreflective material above the retinal pigment epithelium on spectral domain
      optical coherence tomography. CONCLUSION: Foveal granularity on conventional
      fundus imaging could be correlated with hyperreflective lesions visible on AOSLO.
      We hypothesize that these hyperreflective lesions, "Jampol dots," are the foveal
      corollaries of the same process associated with the classic "dot" lesions in
      MEWDS. Based on the intact photoreceptor mosaic on AOSLO, we surmise that this
      material is accumulating at the level of the retinal pigment epithelium.

PMID- 29190246
TI  - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS OF DEEP CAPILLARY PLEXUS
      MICROISCHEMIA AFTER INTRAVENOUS CHEMOTHERAPY FOR RETINOBLASTOMA.
AB  - PURPOSE: To study changes in the foveal microvascular anatomy using optical
      coherence tomography angiography (OCTA) after intravenous chemotherapy (IVC) for
      retinoblastoma (RB). METHODS: A retrospective comparative case-control series
      included 10 age-matched normal eyes with no documented ocular pathology
      (control), 10 fellow eyes of patients with unilateral RB treated with IVC (RB
      fellow), and 10 eyes with extramacular RB in patients with bilateral RB treated
      with IVC (RB tumor). All eyes were scanned using enhanced depth imaging optical
      coherence tomography and OCTA. Enhanced depth imaging optical coherence
      tomography measurements of central macular thickness and subfoveolar choroidal
      thickness as well as OCTA measurements of foveal avascular zone (FAZ) area in
      superficial (sFAZ) and deep (dFAZ) plexus and capillary density (CD) in the
      superficial (sCD) and deep (dCD) plexus were performed. Comparison among the
      three groups was conducted. RESULTS: Among the three cohorts (control, RB fellow,
      and RB tumor), there was no difference in mean age at measurement (12, 10, and 12
      years) and mean interval between last IVC and OCTA (RB fellow and RB tumor) (9,
      10 years). Optical coherence tomography and OCTA revealed no significant
      difference in central macular thickness (all P >= 0.161), choroidal thickness
      (all P >= 0.066), sFAZ (all P >= 0.618), dFAZ (all P >= 0.610), and sCD (all P >=
      0.638) comparing controls versus RB fellow, controls versus RB tumor, and RB
      fellow versus RB tumor. By contrast, mean dCD was significantly greater in
      controls (52%), compared with both RB fellow (49%, P = 0.026) and RB tumor (48%,
      P = 0.028) groups, but no difference was found between RB fellow and RB tumor
      (49% vs. 48%, P = 0.515). LogMAR visual acuity showed no difference among the
      three groups (all P >= 0.150). CONCLUSION: At mean 10-year follow-up, slight
      reduction in dCD seems to occur after IVC for RB without alterations in central
      macular thickness, choroidal thickness, FAZ, or sCD and without visual
      compromise.

PMID- 29190247
TI  - EFFICACY OF DOUBLE DOSE PHOTODYNAMIC THERAPY FOR CIRCUMSCRIBED CHOROIDAL
      HEMANGIOMA.
AB  - PURPOSE: To evaluate the efficacy of photodynamic therapy using a double dose of
      verteporfin for patients with circumscribed choroidal hemangioma. METHODS: This
      retrospective comparative case series evaluated data from 10 patients who were
      treated using double dose photodynamic therapy (12 mg/m) and seven patients who
      were treated using the standard dose (6 mg/m). A laser was applied with a radiant
      exposure of 50 J/cm. The ophthalmologic examinations were performed at baseline
      and 1 year after the treatment and included best-corrected visual acuity, slit
      lamp biomicroscopy, fundus examination, spectral domain optical coherence
      tomography, and B-scan ultrasonography. RESULTS: The mean age in the double dose
      group was 51.60 years, compared with 50.57 years in the standard-dose group. The
      only significant difference between the two groups' baseline characteristics was
      observed in their initial tumor heights. Foveal center thickness, subretinal
      fluid, and subfoveal choroidal thickness decreased significantly at 1 year after
      treatment in both groups. Tumor height and the greatest linear dimension of the
      tumor's base only decreased significantly in the double dose group (P = 0.031).
      Both groups did not experience significant visual improvements. CONCLUSION:
      Double dose photodynamic therapy was effective and safe for treating
      circumscribed choroidal hemangioma and provided better tumor regression with
      similar resorption of subretinal fluid, compared with standard-dose photodynamic
      therapy.

PMID- 29190248
TI  - COMBINING EXTERNAL NEEDLE DRAINAGE AND SCLERAL BUCKLING WITH VITRECTOMY FOR THE
      REPAIR OF BULLOUS RETINAL DETACHMENTS.
AB  - PURPOSE: To describe a technique of combined scleral buckle with external needle
      drainage and vitrectomy in the treatment of bullous exudative retinal detachment,
      schisis detachment, or bullous retinoschisis threatening the fovea. METHODS: A
      retrospective chart review of four eyes of four patients who underwent the
      procedure described. RESULTS: Four eyes of four patients who underwent combined
      scleral buckling with external needle drainage and vitrectomy by a single surgeon
      for a bullous exudative retinal detachment, schisis detachment, or bullous
      retinoschisis threatening the fovea were included in this series. All four
      patients were attached after a single surgical intervention. No patient developed
      complications from the external drainage. CONCLUSION: External needle drainage of
      bullous subretinal or intraschisis fluid in combination with vitrectomy is a
      successful technique for treating bullous exudative retinal detachments, schisis
      detachment, or foveal-threatening retinoschisis. The technique avoids many
      complications associated with conventional drainage procedures. Long-term results
      seem promising because of extended follow-up demonstrating sustained anatomical
      success with a single intervention.

PMID- 29190249
TI  - COMPARISON OF 3 MM * 3 MM VERSUS 6 MM * 6 MM OPTICAL COHERENCE TOMOGRAPHY
      ANGIOGRAPHY SCAN SIZES IN THE EVALUATION OF NON-PROLIFERATIVE DIABETIC
      RETINOPATHY.
AB  - PURPOSE: To evaluate the utility of different optical coherence tomography
      angiography scan protocols in evaluating retinal changes in non-proliferative
      diabetic retinopathy. METHODS: Patients were imaged with the RTVue XR Avanti OCT
      3 mm * 3 mm and 6 mm * 6 mm "Angio Retina" scan protocols. Ability to clearly
      delineate the foveal avascular zone (FAZ), FAZ remodeling, microaneurysms,
      capillary nonperfusion, motion, and doubling artifacts were evaluated. RESULTS:
      Forty-six eyes from 27 patients were enrolled. Eighty-nine percent of 3 mm * 3 mm
      versus 59% of 6 mm * 6 mm scans clearly delineated the FAZ (P = 0.001). Eighty
      percent of 3 mm * 3 mm versus 43% of 6 mm * 6 mm scans demonstrated FAZ
      remodeling (P = 0.0002). Microaneurysms were detected by 57% of 6 mm * 6 mm and
      35% of 3 mm * 3 mm scans (P = 0.003). Capillary nonperfusion was detected in 87%
      of 3 mm * 3 mm scans versus 89% of 6 mm * 6 mm scans (P = 0.99). No significant
      differences were noted in the incidence of artifacts between the scan sizes
      (motion artifact P = 0.29 and doubling artifact P = 0.29). CONCLUSION: 3 mm * 3
      mm scan delineated FAZ and remodeling better than 6 mm * 6 mm scan, likely
      because of its higher scan density. 6 mm * 6 mm scans detected microaneurysms
      more readily than 3 mm * 3 mm, likely because of its larger scan area. There were
      utility for both 3 mm * 3 mm and 6 mm * 6 mm scans when evaluating these
      patients.

PMID- 29190250
TI  - CELLULAR IMAGING OF THE TAPETAL-LIKE REFLEX IN CARRIERS OF RPGR-ASSOCIATED
      RETINOPATHY.
AB  - PURPOSE: To examine the features of the tapetal-like reflex (TLR) in female
      carriers of RPGR-associated retinopathy by means of adaptive optics scanning
      light ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography.
      METHODS: Nine molecularly confirmed RPGR carriers and three healthy controls
      underwent ocular examination and the following retinal imaging modalities: color
      photography, near-infrared reflectance, fundus autofluorescence, spectral domain
      optical coherence tomography, and AOSLO. After identifying TLR areas across all
      imaging modalities, normalized local contrast of outer retinal bands on spectral
      domain optical coherence tomography was calculated and AOSLO-acquired
      photoreceptor mosaic analysis was performed. RESULTS: Seven carriers had TLR
      areas, which colocalized with increased rod photoreceptor reflectivity on
      confocal AOSLO and reduced cone photoreceptor densities. Parafoveal TLR areas
      also exhibited reduced local contrast (i.e., increased reflectivity) of the outer
      retinal bands on spectral domain optical coherence tomography (inner segment
      ellipsoid zone and outer segment interdigitation zone). Healthy controls did not
      show TLR. CONCLUSION: The cellular resolution provided by AOSLO affords the
      characterization of the photoreceptor mosaic in RPGR carriers with a TLR.
      Features revealed include reduced cone densities, increased cone inner segment
      diameters, and increased rod outer segment reflectivity.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.

PMID- 29190251
TI  - Correspondence.

PMID- 29190252
TI  - AIR/FLUID-DROPPING TECHNIQUE FOR INTRACAPSULAR DISTILLED WATER APPLICATION: A
      Vitrectomy Approach for Selective Targeting of Lens Epithelial Cells.
AB  - PURPOSE: We describe a simplified technique of intracapsular distilled water
      application for targeting lens epithelial cells using vitrectomy approach of
      fluid-air exchange and to evaluate the reliability and safety of this technique.
      METHODS: Consecutive patients with cataract were randomly assigned to treatment
      group and control group. After the nucleus removal and cortical aspiration, the
      space of anterior chamber and capsular bag were maintained with continuous
      infusion of sterile air by using fluid-air exchange technique through side-port
      incision. Distilled water was dropped into the capsular bag using a specially
      designed syringe. A concave air-fluid surface (a physical phenomenon) insured the
      contact of distilled water with the inner surface of the capsule without
      overflowing from the bag. The distilled water remained in place for 3 minutes and
      was then removed by the syringe. RESULTS: No intraoperative surgical complication
      was observed, and no damage to adjacent intraocular structures was observed
      during the postoperative follow-up. There was no statistical difference of
      corneal endothelial cell loss between the treatment group and the control group.
      Histological study confirmed damage to the lens epithelial cells from anterior
      capsular specimens treated by the technique. CONCLUSION: The simplified technique
      using vitrectomy approach is safe and specific for targeting lens epithelial
      cells without associated complications.

PMID- 29190253
TI  - Reply.

PMID- 29190255
TI  - Relation of antifactor-Xa peak levels and venous thromboembolism after trauma.
AB  - BACKGROUND: No previous studies have established the optimal antifactor Xa (anti
      Xa) level to guide thromboprophylaxis (TPX) dosing with enoxaparin in trauma
      patients. We hypothesize that achieving 0.2-0.4 IU/mL anti-Xa will decrease
      venous thromboembolism (VTE) rates after trauma. METHODS: This was a
      retrospective review of 194 intensive care unit patients sustaining blunt or
      penetrating trauma from January 2015 to March 2017. All received initial
      enoxaparin (30 mg BID subcutaneous) and mechanical devices for TPX. Peak anti-Xa
      levels were drawn after each third dose. The enoxaparin dose was adjusted up to a
      maximum of 60 mg BID subcutaneous until a peak level of 0.2-0.4 IU/mL was
      achieved. Data are expressed as mean +/- SD if parametric or median (IQR) if not.
      RESULTS: The Greenfield Risk Assessment Profile score was 9 +/- 4, Injury
      Severity Score 23 +/- 14, and hospital length of stay 19 (11-38) days. The
      overall VTE rate was 7.2% (n = 14), with 10 deep venous thromboses (DVT) and 5
      pulmonary emboli (PE). One patient had both a DVT and PE. The median time to VTE
      diagnosis was 14 (7-17) days. In those diagnosed with a VTE, 50.0% (n = 7) never
      reached 0.2-0.4 IU/mL anti-Xa and 42.8% (n = 6) were diagnosed with a VTE after
      achieving these levels. Prophylactic levels were achieved initially in 64 (33.0%)
      patients, and achieved later in 38 (19.6%) additional patients, giving an overall
      prophylactic rate of 52.6% (n = 102). There were no differences in VTE (6.9% vs.
      7.6%, p = 0.841), DVT (3.9% vs. 6.5%, p = 0.413), or PE (3.9% vs. 1.1%, p =
      0.213) rates between those who became prophylactic and those who did not.
      CONCLUSIONS: There was no difference in VTE incidence between those achieving
      anti-Xa peak levels of 0.2-0.4 IU/mL and those who did not. Furthermore, these
      levels were never achieved in some trauma patients despite repeated dosing over a
      >10-day period. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 29190254
TI  - Fibrinolysis shutdown is associated with a fivefold increase in mortality in
      trauma patients lacking hypersensitivity to tissue plasminogen activator.
AB  - BACKGROUND: Fibrinolysis shutdown (SD) is an independent risk factor for
      increased mortality in trauma. High levels of plasminogen activator inhibitor-1
      (PAI-1) directly binding tissue plasminogen activator (t-PA) is a proposed
      mechanism for SD; however, patients with low PAI-1 levels present to the hospital
      with a rapid TEG (r-TEG) LY30 suggestive SD. We therefore hypothesized that two
      distinct phenotypes of SD exist, one, which is driven by t-PA inhibition, whereas
      another is due to an inadequate t-PA release in response to injury. METHODS:
      Trauma activations from our Level I center between 2014 and 2016 with blood
      collected within an hour of injury were analyzed with r-TEG and a modified TEG
      assay to quantify fibrinolysis sensitivity using exogenous t-PA (t-TEG). Using
      the existing r-TEG thresholds for SD (<0.9%), physiologic (LY30 0.9-2.9%), and
      hyperfibrinolysis (LY30 > 2.9%) patients were stratified into phenotypes. A t-TEG
      LY30 greater than 95th percentile of healthy volunteers (n = 140) was classified
      as t-PA hypersensitive and used to subdivide phenotypes. A nested cohort had t-PA
      and PAI-1 activity levels measured in addition to proteomic analysis of
      additional fibrinolytic regulators. RESULTS: This study included 398 patients
      (median New Injury Severity Score, 18), t-PA-Sen was present in 27% of patients.
      Shutdown had the highest mortality rate (20%) followed by hyperfibinolysis (16%)
      and physiologic (9% p = 0.020). In the non-t-PA hypersensitive cohort, SD had a
      fivefold increase in mortality (15%) compared with non-SD patients (3%; p =
      0.003) which remained significant after adjusting for Injury Severity Score and
      age (p = 0.033). Overall t-PA activity (p = 0.002), PAI-1 (p < 0.001), and t
      PA/PAI-1 complex levels (p = 0.006) differed between the six phenotypes, and 54%
      of fibrinolytic regulator proteins analyzed (n = 19) were significantly
      different. CONCLUSION: In conclusion, acute fibrinolysis SD is not caused by a
      single etiology, and is clearly associated with PAI-1 activity. The differential
      phenotypes require an ongoing investigation to identify the optimal resuscitation
      strategy for these patients. LEVEL OF EVIDENCE: Prognostic, level III.

PMID- 29190256
TI  - Time to aortic occlusion: It's all about access.
AB  - INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA)
      is a less invasive method of proximal aortic occlusion compared with
      resuscitative thoracotomy with aortic cross-clamping (RTACC). This study compared
      time to aortic occlusion with REBOA and RTACC, both including and excluding time
      required for common femoral artery (CFA) cannulation. METHODS: This was a
      retrospective, single-institution review of REBOA or RTACC performed between
      February 2013 and January 2016. Time of skin incision to aortic cross-clamp for
      RTACC, time required for CFA cannulation by percutaneous and open methods, and
      time from guide-wire insertion to balloon inflation at Zone 1 for REBOA, were
      obtained from videographic recordings. RESULTS: Eighteen RTACC and 21 REBOAs were
      performed. Median (Q1, Q3) time from skin incision to aortic cross-clamping was
      317 seconds (227, 551 seconds). Median (Q1, Q3) time from start of arterial
      access to Zone 1 balloon occlusion was 474 seconds (431, 572 seconds) (vs. RTACC,
      p = 0.01). All REBOA procedures were performed with the same device. The median
      time to complete CFA cannulation was 247 seconds (range, 164-343 seconds), with
      no difference between percutaneous or open procedures (p = 0.07). The median (Q1,
      Q3) time to aortic occlusion in REBOA once arterial access had been established
      was 245 seconds (179, 295.5 seconds), which was significantly shorter than RTACC
      (p = 0.003). CONCLUSIONS: Once CFA access is achieved, time to aortic occlusion
      is faster with REBOA. Time to aortic occlusion is less than the time required to
      cannulate the CFA either by percutaneous or open approaches, emphasizing the
      importance of accurate and expedient CFA access. Resuscitative endovascular
      balloon occlusion of the aorta may represent a feasible alternative to
      thoracotomy for aortic occlusion. Time to aortic occlusion will likely decrease
      with the advent of newer REBOA technology. The rate-limiting portion of REBOA
      continues to be obtaining CFA access. LEVEL OF EVIDENCE: Therapeutic, level V.

PMID- 29190257
TI  - The trauma center is too late: Major limb trauma without a pre-hospital
      tourniquet has increased death from hemorrhagic shock.
AB  - BACKGROUND: To date, no civilian studies have demonstrated that pre-hospital (PH)
      tourniquets improve survival. We hypothesized that late, trauma center (TC)
      tourniquet use would increase death from hemorrhagic shock compared to early (PH)
      placement. METHODS: All patients arriving to a Level 1, urban TC between October
      2008 and January 2016 with a tourniquet placed before (T-PH) or after arrival to
      the TC (T-TC) were evaluated. Cases were assigned the following designations:
      indicated (absolute indication [vascular injury requiring repair/ligation,
      operation within 2 hours for extremity injury, or traumatic amputation] or
      relative indication [major musculoskeletal/soft tissue injury requiring operation
      2-8 hours after arrival, documented large blood loss]) or non-indicated. Outcomes
      were death from hemorrhagic shock, physiology upon arrival to the TC, and massive
      transfusion requirements. After univariate analysis, logistic regression was
      carried out to assess independent predictors of death from hemorrhagic shock.
      RESULTS: A total of 306 patients received 326 tourniquets for injuries to 157
      upper and 147 lower extremities. Two hundred eighty-one (92%) had an indication
      for placement. Seventy percent of patients had a blunt mechanism of injury. T-TC
      patients arrived with a lower systolic blood pressure (SBP, 101 [86, 123] vs. 125
      [100, 145] mm Hg, p < 0.001), received more transfusions in the first hour of
      arrival (55% vs. 34%, p = 0.02), and had a greater mortality from hemorrhagic
      shock (14% vs. 3.0%, p = 0.01). When controlling for year of admission, mechanism
      of injury and shock upon arrival (SBP <=90 mm Hg or HR >=120 bpm or base deficit
      <= 4) indicated T-TC had a 4.5-fold increased odds of death compared to T-PH (OR
      4.5, 95% CI 1.23-16.4, p = 0.02). CONCLUSIONS: Waiting until TC arrival to
      control hemorrhage with a tourniquet was associated with worsened blood pressure
      and increased transfusion within the first hour of arrival. In routine civilian
      trauma patients, delaying to T-TC was associated with 4.5-fold increased odds of
      mortality from hemorrhagic shock. LEVEL OF EVIDENCE: Level IV.

PMID- 29190258
TI  - Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet
      Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus
      Immune Suppression: Erratum.

PMID- 29190259
TI  - Gene Silencing in Rat-Liver and Limb Grafts by Rapid Injection of Small
      Interference RNA: Erratum.

PMID- 29190260
TI  - Transplantation in Ireland: Erratum.

PMID- 29190261
TI  - Comparison of Stent-Assisted Coil Placement and Coiling-Only for the Treatment of
      Ruptured Intracranial Aneurysms.
AB  - BACKGROUND The use of a stent during the acute post-hemorrhage period is
      controversial. We conducted a retrospective analysis on the clinical and
      angiographic outcomes of the ruptured aneurysms that were embolized with stent
      assisted coiling or coiling-only. MATERIAL AND METHODS We reviewed data of 279
      patients with 279 ruptured intracranial aneurysms who underwent coil embolization
      between July 2004 and June 2015. The baseline data on age, sex, medical history,
      aneurysm size, location, and Hunt and Hess grade were recorded. RESULTS One
      hundred and thirteen aneurysms were treated with stent-assisted coiling. Adverse
      events occurred in similar proportions of patients in the two groups (11.5% in
      the stenting group and 9.0% in the coiling alone group). The incidence of
      permanent disabling neurologic deficit was also similar in the two groups (7.1%
      and 5.4% in the stenting group and coiling alone group respectively). Clinical
      follow-up data were available in 207 patients with a median period of 28 months.
      Angiographic follow-up was available in 106 aneurysms with a median period of 7.5
      months. Clinical outcomes were correlated with adverse events (p=0.043, odds
      ratio=4.59), large aneurysms (p=0.013, odds ratio=10.24), and Hunt and Hess grade
      (p=0.001, odds ratio=13.51). Stent-assisted coiling for ruptured aneurysm, as
      compared with coiling-only, was not associated with an increased incidence of
      poor clinical outcome at follow-up. Aneurysm-occlusion status at follow-up were
      correlated with stent placement (p<0.001, odds ratio=5.85) and initial aneurysm
      occlusion status (p=0.027, odds ratio=3.78). CONCLUSIONS Compared with coiling
      only, stent-assisted coil placement may have better durability, with comparable
      safety for ruptured intracranial aneurysm.

PMID- 29190262
TI  - Notes from the Field: Absence of Asymptomatic Mumps Virus Shedding Among
      Vaccinated College Students During a Mumps Outbreak - Washington, February-June
      2017.

PMID- 29190263
TI  - Scale-Up of Voluntary Medical Male Circumcision Services for HIV Prevention - 12
      Countries in Southern and Eastern Africa, 2013-2016.
AB  - Countries in Southern and Eastern Africa have the highest prevalence of human
      immunodeficiency virus (HIV) infection in the world; in 2015, 52% (approximately
      19 million) of all persons living with HIV infection resided in these two
      regions.* Voluntary medical male circumcision (VMMC) reduces the risk for
      heterosexually acquired HIV infection among males by approximately 60% (1). As
      such, it is an essential component of the Joint United Nations Programme on
      HIV/AIDS (UNAIDS) strategy for ending acquired immunodeficiency syndrome (AIDS)
      by 2030 (2). Substantial progress toward achieving VMMC targets has been made in
      the 10 years since the World Health Organization (WHO) and UNAIDS recommended
      scale-up of VMMC for HIV prevention in 14 Southern and Eastern African countries
      with generalized HIV epidemics and low male circumcision prevalence (3).? This
      has been enabled in part by nearly $2 billion in cumulative funding through the
      President's Emergency Plan for AIDS Relief (PEPFAR), administered through
      multiple U.S. governmental agencies, including CDC, which has supported nearly
      half of all PEPFAR-supported VMMCs to date. Approximately 14.5 million VMMCs were
      performed globally during 2008-2016, which represented 70% of the original target
      of 20.8 million VMMCs in males aged 15-49 years through 2016 (4). Despite falling
      short of the target, these VMMCs are projected to avert 500,000 HIV infections by
      the end of 2030 (4). However, UNAIDS has estimated an additional 27 million VMMCs
      need to be performed by 2021 to meet the Fast Track targets (2). This report
      updates a previous report covering the period 2010-2012, when VMMC implementing
      partners supported by CDC performed approximately 1 million VMMCs in nine
      countries (5). During 2013-2016, these implementing partners performed nearly 5
      million VMMCs in 12 countries. Meeting the global target will require redoubling
      current efforts and introducing novel strategies that increase demand among
      subgroups of males who have historically been reluctant to undergo VMMC.

PMID- 29190264
TI  - Fractional-Dose Inactivated Poliovirus Vaccine Campaign - Sindh Province,
      Pakistan, 2016.
AB  - Following the declaration of eradication of wild poliovirus (WPV) type 2 in
      September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally
      to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission;
      all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in
      April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a
      potential public health emergency and might indicate the need for supplementary
      immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a
      sewage sample taken from an environmental surveillance site in Hyderabad, Sindh
      province, Pakistan. Possible vaccination activities in response to VDPV2
      isolation include the use of injectable inactivated polio vaccine (IPV), which
      poses no risk for vaccine-derived poliovirus transmission. Fractional-dose,
      intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been
      developed to more efficiently manage limited IPV supplies. fIPV has been shown in
      some studies to be noninferior to full-dose IPV (5,6) and was used successfully
      in response to a similar detection of a single VDPV2 isolate from sewage in India
      (7). Injectable fIPV was used for response activities in Hyderabad and three
      neighboring districts. This report describes the findings of an assessment of
      preparatory activities and subsequent implementation of the fIPV campaign.
      Despite achieving high coverage (>80%), several operational challenges were
      noted. The lessons learned from this campaign could help to guide the planning
      and implementation of future fIPV vaccination activities.

PMID- 29190265
TI  - QuickStats: Percentage* of Adults Aged 20-64 Years With a Fasting Test in the
      Past 12 Months for High Blood Sugar or Diabetes,? by Race/EthnicityS - National
      Health Interview Survey,  United States, 2011 and 2016.
AB  - The percentage of U.S. adults aged 20-64 years who had a fasting test for high
      blood sugar or diabetes in the past 12 months increased from 39.7% in 2011 to
      45.7% in 2016. From 2011 to 2016, there was an increase in the percentage for all
      racial/ethnic groups examined: Hispanic (38.3% to 43.0%), non-Hispanic white
      (39.6% to 46.5%), non-Hispanic black (41.2% to 44.9%), and non-Hispanic Asian
      (41.5% to 49.6%) adults. In 2011, there was no statistically significant
      difference among the four groups examined, but in 2016, Hispanic adults were less
      likely than non-Hispanic white and non-Hispanic Asian adults to have had a
      fasting test, and non-Hispanic Asian adults were more likely than non-Hispanic
      black adults to have had one.

PMID- 29190266
TI  - Announcement: Community Preventive Services Task Force Recommendation for Text
      Messaging Interventions to Improve Medication Adherence for Chronic Disease
      Management.

PMID- 29190267
TI  - Vital Signs: Human Immunodeficiency Virus Testing and Diagnosis Delays - United
      States.
AB  - BACKGROUND: Persons unaware of their human immunodeficiency virus (HIV) infection
      account for approximately 40% of ongoing transmissions in the United States.
      Persons are unaware of their infection because of delayed HIV diagnoses that
      represent substantial missed opportunities to improve health outcomes and prevent
      HIV transmission. METHODS: Data from CDC's National HIV Surveillance System were
      used to estimate, among persons with HIV infection diagnosed in 2015, the median
      interval (and range) from infection to diagnosis (diagnosis delay), based on the
      first CD4 test after HIV diagnosis and a CD4 depletion model indicating disease
      progression and, among persons living with HIV in 2015, the percentage with
      undiagnosed infection. Data from CDC's National HIV Behavioral Surveillance were
      analyzed to determine the percentage of persons at increased risk for HIV
      infection who had tested in the past 12 months and who had missed opportunities
      for testing. RESULTS: An estimated 15% of persons living with HIV in 2015 were
      unaware of their infection. Among the 39,720 persons with HIV infection diagnosed
      in 2015, the estimated median diagnosis delay was 3.0 years (interquartile range
      = 0.7-7.8 years); diagnosis delay varied by race/ethnicity (from 2.2 years among
      whites to 4.2 years among Asians) and transmission category (from 2.0 years among
      females who inject drugs to 4.9 years among heterosexual males). Among persons
      interviewed through National HIV Behavioral Surveillance, 71% of men who have sex
      with men, 58% of persons who inject drugs, and 41% of heterosexual persons at
      increased risk for HIV infection reported testing in the past 12 months. In each
      risk group, at least two thirds of persons who did not have an HIV test had seen
      a health care provider in the past year. CONCLUSIONS: Delayed HIV diagnoses
      continue to be substantial for some population groups and prevent early entry to
      care to improve health outcomes and reduce HIV transmission to others.
      IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health care providers and others
      providing HIV testing can reduce HIV-related adverse health outcomes and risk for
      HIV transmission by implementing routine and targeted HIV testing to decrease
      diagnosis delays.

PMID- 29190268
TI  - Synthetic Cannabinoid and Mitragynine Exposure of Law Enforcement Agents During
      the Raid of an Illegal Laboratory - Nevada, 2014.
AB  - Synthetic cannabinoids (SCs), commonly known by the street name "Spice," are
      designer drugs of abuse that mimic the psychoactive effects of marijuana.
      Intentional SC use has resulted in multiple toxicities (1,2), but little is known
      about occupational SC exposure. After a federal agency's law enforcement
      personnel in Nevada reported irritability and feeling "high" after raiding
      illegal SC laboratories and processing seized SCs, a request for a health hazard
      evaluation was made by the agency to CDC's National Institute for Occupational
      Safety and Health (NIOSH) in 2014 to evaluate agents' occupational SC exposures.
      After making the request for a health hazard evaluation, federal agents conducted
      a raid of an illegal SC laboratory, with assistance from local law enforcement
      and Drug Enforcement Administration (DEA) personnel and with NIOSH investigators
      observing from a distance. After the raid, agents collected and processed
      material evidence. NIOSH investigators tested agents' urine for SC levels before
      and after the raid and measured SCs in the air and on surfaces after the raid.
      DEA determined that AB-PINACA (an SC compound) and mitragynine (a plant material
      with opium-like effects, also known as "kratom") were present in the illegal
      laboratory. AB-PINACA, its metabolites, and mitragynine were not detected in
      agents' urine before the raid; however, one or more of these substances was found
      in the urine of six of nine agents after the raid and processing of the SC
      evidence. AB-PINACA was detected in one surface wipe sample from the SC
      laboratory; none was detected in the air in the laboratory or in the offices of
      the law enforcement agency where the materials were processed after the raid. No
      policies were in place regarding work practices and use of personal protective
      equipment (PPE) during raids and evidence processing. To protect agents from SC
      exposures, NIOSH recommended that the agency require agents to wear a minimum
      level of PPE (e.g., protective gloves and disposable clothing) and undergo
      training in PPE and in handling and storing of contaminated evidence from SC
      laboratory raids. Showers and locker rooms also need to be provided so that
      agents can reduce contamination and prevent take-home exposure.

PMID- 29190269
TI  - SPOTs fill a major gap in RNA quantification.

PMID- 29190270
TI  - Microscopy: hello, adaptive optics.

PMID- 29190271
TI  - MDsrv: viewing and sharing molecular dynamics simulations on the web.

PMID- 29190272
TI  - LiteMol suite: interactive web-based visualization of large-scale macromolecular
      structure data.

PMID- 29190273
TI  - Mass spectrometry imaging goes three dimensional.

PMID- 29190274
TI  - Accessible virtual reality of biomolecular structural models using the Autodesk
      Molecule Viewer.

PMID- 29190275
TI  - Correction: Approach-Induced Biases in Human Information Sampling.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.2000638.].

PMID- 29190276
TI  - Public health risks from subclinical variant CJD.

PMID- 29190278
TI  - Can narrow-bandwidth light from UV-A to green alter secondary plant metabolism
      and increase Brassica plant defenses against aphids?
AB  - Light of different wavelengths is essential for plant growth and development.
      Short-wavelength radiation such as UV can shift the composition of flavonoids,
      glucosinolates, and other plant metabolites responsible for enhanced defense
      against certain herbivorous insects. The intensity of light-induced, metabolite
      based resistance is plant- and insect species-specific and depends on herbivore
      feeding guild and specialization. The increasing use of light-emitting diodes
      (LEDs) in horticultural plant production systems in protected environments
      enables the creation of tailor-made light scenarios for improved plant
      cultivation and induced defense against herbivorous insects. In this study,
      broccoli (Brassica oleracea var. italica) plants were grown in a climate chamber
      under broad spectra photosynthetic active radiation (PAR) and were additionally
      treated with the following narrow-bandwidth light generated with LEDs: UV-A (365
      nm), violet (420 nm), blue (470 nm), or green (515 nm). We determined the
      influence of narrow-bandwidth light on broccoli plant growth, secondary plant
      metabolism (flavonol glycosides and glucosinolates), and plant-mediated light
      effects on the performance and behavior of the specialized cabbage aphid
      Brevicoryne brassicae. Green light increased plant height more than UV-A, violet,
      or blue LED treatments. Among flavonol glycosides, specific quercetin and
      kaempferol glycosides were increased under violet light. The concentration of 3
      indolylmethyl glucosinolate in plants was increased by UV-A treatment. B.
      brassicae performance was not influenced by the different light qualities, but in
      host-choice tests, B. brassicae preferred previously blue-illuminated plants (but
      not UV-A-, violet-, or green-illuminated plants) over control plants.

PMID- 29190280
TI  - From rationality to cooperativeness: The totally mixed Nash equilibrium in Markov
      strategies in the iterated Prisoner's Dilemma.
AB  - In this research, the social behavior of the participants in a Prisoner's Dilemma
      laboratory game is explained on the basis of the quantal response equilibrium
      concept and the representation of the game in Markov strategies. In previous
      research, we demonstrated that social interaction during the experiment has a
      positive influence on cooperation, trust, and gratefulness. This research shows
      that the quantal response equilibrium concept agrees only with the results of
      experiments on cooperation in Prisoner's Dilemma prior to social interaction.
      However, quantal response equilibrium does not explain of participants' behavior
      after social interaction. As an alternative theoretical approach, an examination
      was conducted of iterated Prisoner's Dilemma game in Markov strategies. We built
      a totally mixed Nash equilibrium in this game; the equilibrium agrees with the
      results of the experiments both before and after social interaction.

PMID- 29190279
TI  - malERA: An updated research agenda for characterising the reservoir and measuring
      transmission in malaria elimination and eradication.
AB  - This paper summarises key advances in defining the infectious reservoir for
      malaria and the measurement of transmission for research and programmatic use
      since the Malaria Eradication Research Agenda (malERA) publication in 2011. Rapid
      and effective progress towards elimination requires an improved understanding of
      the sources of transmission as well as those at risk of infection. Characterising
      the transmission reservoir in different settings will enable the most appropriate
      choice, delivery, and evaluation of interventions. Since 2011, progress has been
      made in a number of areas. The extent of submicroscopic and asymptomatic
      infections is better understood, as are the biological parameters governing
      transmission of sexual stage parasites. Limitations of existing transmission
      measures have been documented, and proof-of-concept has been established for new
      innovative serological and molecular methods to better characterise transmission.
      Finally, there now exists a concerted effort towards the use of ensemble datasets
      across the spectrum of metrics, from passive and active sources, to develop more
      accurate risk maps of transmission. These can be used to better target
      interventions and effectively monitor progress toward elimination. The success of
      interventions depends not only on the level of endemicity but also on how rapidly
      or recently an area has undergone changes in transmission. Improved understanding
      of the biology of mosquito-human and human-mosquito transmission is needed
      particularly in low-endemic settings, where heterogeneity of infection is
      pronounced and local vector ecology is variable. New and improved measures of
      transmission need to be operationally feasible for the malaria programmes.
      Outputs from these research priorities should allow the development of a set of
      approaches (applicable to both research and control programmes) that address the
      unique challenges of measuring and monitoring transmission in near-elimination
      settings and defining the absence of transmission.

PMID- 29190277
TI  - malERA: An updated research agenda for basic science and enabling technologies in
      malaria elimination and eradication.
AB  - Basic science holds enormous power for revealing the biological mechanisms of
      disease and, in turn, paving the way toward new, effective interventions.
      Recognizing this power, the 2011 Research Agenda for Malaria Eradication included
      key priorities in fundamental research that, if attained, could help accelerate
      progress toward disease elimination and eradication. The Malaria Eradication
      Research Agenda (malERA) Consultative Panel on Basic Science and Enabling
      Technologies reviewed the progress, continuing challenges, and major
      opportunities for future research. The recommendations come from a literature of
      published and unpublished materials and the deliberations of the malERA Refresh
      Consultative Panel. These areas span multiple aspects of the Plasmodium life
      cycle in both the human host and the Anopheles vector and include critical,
      unanswered questions about parasite transmission, human infection in the liver,
      asexual-stage biology, and malaria persistence. We believe an integrated approach
      encompassing human immunology, parasitology, and entomology, and harnessing new
      and emerging biomedical technologies offers the best path toward addressing these
      questions and, ultimately, lowering the worldwide burden of malaria.

PMID- 29190281
TI  - Internet-based biosurveillance methods for vector-borne diseases: Are they novel
      public health tools or just novelties?
AB  - Internet-based surveillance methods for vector-borne diseases (VBDs) using "big
      data" sources such as Google, Twitter, and internet newswire scraping have
      recently been developed, yet reviews on such "digital disease detection" methods
      have focused on respiratory pathogens, particularly in high-income regions. Here,
      we present a narrative review of the literature that has examined the performance
      of internet-based biosurveillance for diseases caused by vector-borne viruses,
      parasites, and other pathogens, including Zika, dengue, other arthropod-borne
      viruses, malaria, leishmaniasis, and Lyme disease across a range of settings,
      including low- and middle-income countries. The fundamental features, advantages,
      and drawbacks of each internet big data source are presented for those with
      varying familiarity of "digital epidemiology." We conclude with some of the
      challenges and future directions in using internet-based biosurveillance for the
      surveillance and control of VBD.

PMID- 29190283
TI  - Sonic Kayaks: Environmental monitoring and experimental music by citizens.
AB  - The Sonic Kayak is a musical instrument used to investigate nature and developed
      during open hacklab events. The kayaks are rigged with underwater environmental
      sensors, which allow paddlers to hear real-time water temperature sonifications
      and underwater sounds, generating live music from the marine world. Sensor data
      is also logged every second with location, time and date, which allows for fine
      scale mapping of water temperatures and underwater noise that was previously
      unattainable using standard research equipment. The system can be used as a
      citizen science data collection device, research equipment for professional
      scientists, or a sound art installation in its own right.

PMID- 29190282
TI  - Experience-dependent olfactory behaviors of the parasitic nematode
      Heligmosomoides polygyrus.
AB  - Parasitic nematodes of humans and livestock cause extensive disease and economic
      loss worldwide. Many parasitic nematodes infect hosts as third-stage larvae,
      called iL3s. iL3s vary in their infection route: some infect by skin penetration,
      others by passive ingestion. Skin-penetrating iL3s actively search for hosts
      using host-emitted olfactory cues, but the extent to which passively ingested
      iL3s respond to olfactory cues was largely unknown. Here, we examined the
      olfactory behaviors of the passively ingested murine gastrointestinal parasite
      Heligmosomoides polygyrus. H. polygyrus iL3s were thought to reside primarily on
      mouse feces, and infect when mice consume feces containing iL3s. However, iL3s
      can also adhere to mouse fur and infect orally during grooming. Here, we show
      that H. polygyrus iL3s are highly active and show robust attraction to host
      feces. Despite their attraction to feces, many iL3s migrate off feces to engage
      in environmental navigation. In addition, H. polygyrus iL3s are attracted to
      mammalian skin odorants, suggesting that they migrate toward hosts. The olfactory
      preferences of H. polygyrus are flexible: some odorants are repulsive for iL3s
      maintained on feces but attractive for iL3s maintained off feces. Experience
      dependent modulation of olfactory behavior occurs over the course of days and is
      mediated by environmental carbon dioxide (CO2) levels. Similar experience
      dependent olfactory plasticity occurs in the passively ingested ruminant
      parasitic nematode Haemonchus contortus, a major veterinary parasite. Our results
      suggest that passively ingested iL3s migrate off their original fecal source and
      actively navigate toward hosts or new host fecal sources using olfactory cues.
      Olfactory plasticity may be a mechanism that enables iL3s to switch from
      dispersal behavior to host-seeking behavior. Together, our results demonstrate
      that passively ingested nematodes do not remain inactive waiting to be swallowed,
      but rather display complex sensory-driven behaviors to position themselves for
      host ingestion. Disrupting these behaviors may be a new avenue for preventing
      infections.

PMID- 29190284
TI  - Listeria monocytogenes switches from dissemination to persistence by adopting a
      vacuolar lifestyle in epithelial cells.
AB  - Listeria monocytogenes causes listeriosis, a foodborne disease that poses serious
      risks to fetuses, newborns and immunocompromised adults. This intracellular
      bacterial pathogen proliferates in the host cytosol and exploits the host actin
      polymerization machinery to spread from cell-to-cell and disseminate in the host.
      Here, we report that during several days of infection in human hepatocytes or
      trophoblast cells, L. monocytogenes switches from this active motile lifestyle to
      a stage of persistence in vacuoles. Upon intercellular spread, bacteria gradually
      stopped producing the actin-nucleating protein ActA and became trapped in
      lysosome-like vacuoles termed Listeria-Containing Vacuoles (LisCVs).
      Subpopulations of bacteria resisted degradation in LisCVs and entered a slow/non
      replicative state. During the subculture of host cells harboring LisCVs, bacteria
      showed a capacity to cycle between the vacuolar and the actin-based motility
      stages. When ActA was absent, such as in DeltaactA mutants, vacuolar bacteria
      parasitized host cells in the so-called "viable but non-culturable" state (VBNC),
      preventing their detection by conventional colony counting methods. The exposure
      of infected cells to high doses of gentamicin did not trigger the formation of
      LisCVs, but selected for vacuolar and VBNC bacteria. Together, these results
      reveal the ability of L. monocytogenes to enter a persistent state in a subset of
      epithelial cells, which may favor the asymptomatic carriage of this pathogen,
      lengthen the incubation period of listeriosis, and promote bacterial survival
      during antibiotic therapy.

PMID- 29190285
TI  - The interplay of UV and cutaneous papillomavirus infection in skin cancer
      development.
AB  - Cutaneous human papillomaviruses (HPVs) are considered as cofactors for non
      melanoma skin cancer (NMSC) development, especially in association with UVB.
      Extensively studied transgenic mouse models failed to mimic all aspects of virus
      host interactions starting from primary infection to the appearance of a tumor.
      Using the natural model Mastomys coucha, which reflects the human situation in
      many aspects, we provide the first evidence that only UVB and Mastomys natalensis
      papillomavirus (MnPV) infection strongly promote NMSC formation. Using UVB
      exposures that correspond to UV indices of different geographical regions,
      irradiated animals developed either well-differentiated keratinizing squamous
      cell carcinomas (SCCs), still supporting productive infections with high viral
      loads and transcriptional activity, or poorly differentiated non-keratinizing
      SCCs almost lacking MnPV DNA and in turn, early and late viral transcription.
      Intriguingly, animals with the latter phenotype, however, still showed strong
      seropositivity, clearly verifying a preceding MnPV infection. Of note, the mere
      presence of MnPV could induce gammaH2AX foci, indicating that viral infection
      without prior UVB exposure can already perturb genome stability of the host cell.
      Moreover, as shown both under in vitro and in vivo conditions, MnPV E6/E7
      expression also attenuates the excision repair of cyclobutane pyrimidine dimers
      upon UVB irradiation, suggesting a viral impact on the DNA damage response. While
      mutations of Ras family members (e.g. Hras, Kras, and Nras) were absent, the
      majority of SCCs harbored-like in humans-Trp53 mutations especially at two hot
      spots in the DNA-binding domain, resulting in a loss of function that favored
      tumor dedifferentiation, counter-selective for viral maintenance. Such a
      constellation provides a reasonable explanation for making continuous viral
      presence dispensable during skin carcinogenesis as observed in patients with
      NMSC.

PMID- 29190286
TI  - Nucleolar sub-compartments in motion during rRNA synthesis inhibition:
      Contraction of nucleolar condensed chromatin and gathering of fibrillar centers
      are concomitant.
AB  - The nucleolus produces the large polycistronic transcript (47S precursor)
      containing the 18S, 5.8S and 28S rRNA sequences and hosts most of the nuclear
      steps of pre-rRNA processing. Among numerous components it contains condensed
      chromatin and active rRNA genes which adopt a more accessible conformation. For
      this reason, it is a paradigm of chromosome territory organization. Active rRNA
      genes are clustered within several fibrillar centers (FCs), in which they are
      maintained in an open configuration by Upstream Binding Factor (UBF) molecules.
      Here, we used the reproducible reorganization of nucleolar components induced by
      the inhibition of rRNA synthesis by Actinomycin D (AMD) to address the steps of
      the spatiotemporal reorganization of FCs and nucleolar condensed chromatin. To
      reach that goal, we used two complementary approaches: i) time-lapse confocal
      imaging of cells expressing one or several GFP-tagged proteins (fibrillarin, UBF,
      histone H2B) and ii) ultrastructural identification of nucleolar components
      involved in the reorganization. Data obtained by time lapse confocal microscopy
      were analyzed through detailed 3D imaging. This allowed us to demonstrate that
      AMD treatment induces no fusion and no change in the relative position of the
      different nucleoli contained in one nucleus. In contrast, for each nucleolus, we
      observed step by step gathering and fusion of both FCs and nucleolar condensed
      chromatin. To analyze the reorganization of FCs and condensed chromatin at a
      higher resolution, we performed correlative light and electron microscopy
      electron microscopy (CLEM) imaging of the same cells. We demonstrated that
      threads of intranucleolar condensed chromatin are localized in a complex 3D
      network of vacuoles. Upon AMD treatment, these structures coalesce before
      migrating toward the perinucleolar condensed chromatin, to which they finally
      fuse. During their migration, FCs, which are all linked to ICC, are pulled by the
      latter to gather as caps disposed at the periphery of nucleoli.

PMID- 29190287
TI  - Discovery of a rich gene pool of bat SARS-related coronaviruses provides new
      insights into the origin of SARS coronavirus.
AB  - A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in
      horseshoe bats since 2005 in different areas of China. However, these bat SARSr
      CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different
      genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct
      progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance
      of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan
      Province, China. The full-length genomes of 11 newly discovered SARSr-CoV
      strains, together with our previous findings, reveals that the SARSr-CoVs
      circulating in this single location are highly diverse in the S gene, ORF3 and
      ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the
      hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1
      gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave.
      In addition, we report the first discovery of bat SARSr-CoVs highly similar to
      human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV
      strains from this cave were more closely related to SARS-CoV in the non
      structural protein genes ORF1a and 1b compared with those detected elsewhere.
      Recombination analysis shows evidence of frequent recombination events within the
      S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the
      direct progenitor of SARS-CoV may have originated after sequential recombination
      events between the precursors of these SARSr-CoVs. Cell entry studies
      demonstrated that three newly identified SARSr-CoVs with different S protein
      sequences are all able to use human ACE2 as the receptor, further exhibiting the
      close relationship between strains in this cave and SARS-CoV. This work provides
      new insights into the origin and evolution of SARS-CoV and highlights the
      necessity of preparedness for future emergence of SARS-like diseases.

PMID- 29190288
TI  - Hematologic and biochemical differences between two free ranging Yangtze finless
      porpoise populations: The implications of habitat.
AB  - The goals of this study were to compare the serum chemistry and hematology values
      of wild and semi-natural free-ranging Yangtze Finless Porpoises (Neophocaena
      asiaeorientalis ssp. asiaeorientalis) populations and to ascertain how these
      values change with the different environmental condition. For this study, samples
      were collected from 81 YFPs, 35 living in the wild and 46 living in a semi
      natural reserve. Each population was divided into 8 life history categories; Male
      Calf, Female Calf, Juvenile Male, Juvenile Female, Adult Male, Pregnant,
      Lactating and Pregnant plus Lactating. Statistically significant differences in
      the various parameters were observed in the same life history categories for both
      populations. Generally, Lipid Profile, Hepatic Enzymes, Creatine Kinase, Red
      Blood Cells, Hemoglobin, Hematocrit and Neutrophils were significantly higher in
      the Tian-E-Zhou Oxbow population while, Creatinine, Phosphate, Lactate
      Dehydrogenase, Bilirubin and Lymphocytes were significantly higher in the Poyang
      Lake YFPs. Across the groups in the Tian-E-Zhou Oxbow population, a significant
      decrease in serum Albumin, Alkaline Phosphatase and Calcium, while a significant
      increase in the Neutrophils and Platelets was observed. Similarly, in the Poyang
      Lake, Alkaline Phosphatase levels in the Female Calves group, High Density
      Lipoprotein Cholesterol in Lactating group, basophil counts in Pregnant plus
      Lactating group, lymphocytes counts in Juvenile Females group and Globulin and
      Total Protein levels in Pregnant group were significantly higher. This study in
      health assessments can help us to understand the effect of sex, age, reproductive
      status and environmental conditions on the well-being of Yangtze Finless
      Porpoises.

PMID- 29190289
TI  - malERA: An updated research agenda for health systems and policy research in
      malaria elimination and eradication.
AB  - Health systems underpin disease elimination and eradication programmes. In an
      elimination and eradication context, innovative research approaches are needed
      across health systems to assess readiness for programme reorientation, mitigate
      any decreases in effectiveness of interventions ('effectiveness decay'), and
      respond to dynamic and changing needs. The malaria eradication research agenda
      (malERA) Refresh consultative process for the Panel on Health Systems and Policy
      Research identifies opportunities to build health systems evidence and the tools
      needed to eliminate malaria from different zones, countries, and regions and to
      eradicate it globally. The research questions are organised as a portfolio that
      global health practitioners, researchers, and funders can identify with and
      support. This supports the promotion of an actionable and more cohesive approach
      to building the evidence base for scaled-up implementation of findings. Gaps and
      opportunities discussed in the paper include delivery strategies to meet the
      changing dynamics of needs of individuals, environments, and malaria programme
      successes; mechanisms and approaches to best support accelerated policy and
      financial responsiveness at national and global level to ensure timely response
      to evidence and needs, including in crisis situations; and systems' readiness
      tools and decision-support systems.

PMID- 29190290
TI  - Skeletal muscle mitochondrial bioenergetics and associations with myostatin
      genotypes in the Thoroughbred horse.
AB  - Variation in the myostatin (MSTN) gene has been reported to be associated with
      race distance, body composition and skeletal muscle fibre composition in the
      horse. The aim of the present study was to test the hypothesis that MSTN
      variation influences mitochondrial phenotypes in equine skeletal muscle.
      Mitochondrial abundance and skeletal muscle fibre types were measured in whole
      muscle biopsies from the gluteus medius of n = 82 untrained (21 +/- 3 months)
      Thoroughbred horses. Skeletal muscle fibre type proportions were significantly (p
      < 0.01) different among the three MSTN genotypes and mitochondrial content was
      significantly (p < 0.01) lower in the combined presence of the C-allele of SNP
      g.66493737C>T (C) and the SINE insertion 227 bp polymorphism (I). Evaluation of
      mitochondrial complex activities indicated higher combined mitochondrial complex
      I+III and II+III activities in the presence of the C-allele / I allele (p <=
      0.05). The restoration of complex I+III and complex II+III activities following
      addition of exogenous coenzyme Q1 (ubiquinone1) (CoQ1) in vitro in the TT/NN
      (homozygous T allele/homozygous no insertion) cohort indicated decreased coenzyme
      Q in these animals. In addition, decreased gene expression in two coenzyme Q
      (CoQ) biosynthesis pathway genes (COQ4, p <= 0.05; ADCK3, p <= 0.01) in the TT/NN
      horses was observed. This study has identified several mitochondrial phenotypes
      associated with MSTN genotype in untrained Thoroughbred horses and in addition,
      our findings suggest that nutritional supplementation with CoQ may aid to restore
      coenzyme Q activity in TT/NN horses.

PMID- 29190292
TI  - TNF-alpha blockade suppresses pericystic inflammation following anthelmintic
      treatment in porcine neurocysticercosis.
AB  - BACKGROUND: Neurocysticercosis (NCC) is an infection of the brain with the larval
      cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite
      killing resulting in a post inflammatory response and seizures, which generally
      requires corticosteroid treatment to control inflammation. The nature of this
      response and how to best control it is unclear. We investigated the anti
      inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor
      necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on
      the post treatment inflammatory response in naturally infected pigs with
      neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ).
      METHODOLOGY/PRINCIPAL FINDINGS: We followed the methods from a previously
      developed treatment model of NCC in naturally infected swine. The four study
      groups of infected pigs included 3 groups treated with PZQ on day 0: PZQ-treated
      alone (100 mg/kg PO; n = 9), pretreated with dexamethasone (DEX, 0.2 mg/kg IM
      administered on days -1, +1 and +3; n = 6), and pretreated with etanercept (ETN,
      25 mg IM per animal on days -7 and 0; n = 6). The fourth group remained untreated
      (n = 3). As measured by quantitative RT-PCR, ETN pretreatment depressed
      transcription of a wide range of proinflammatory, regulatory and matrix protease
      encoding genes at 120 hr post PZQ treatment in capsules of cysts that
      demonstrated extravasated Evans Blue (EB) (a measure of blood brain barrier
      dysfunction) compared to animals not receiving ETN. Transcription was
      significantly depressed for the proinflammatory genes tumor necrosis factor (TNF)
      alpha, and interferon (IFN)-gamma; the inflammation regulating genes cytotoxic T
      lymphocyte-associated protein (CTLA)4, interleukin (IL)-13 and transforming
      growth factor (TGF)-beta; the tissue remodeling genes matrix metalloprotease
      (MMP)1 and 9, tissue inhibitors of metalloproteases (TIMP)1 and 2, and the genes
      regulating endothelial function vascular endothelial growth factor (VEGF)1,
      angiopoietin (Ang)1, Ang 2, and platelet endothelial cell adhesion molecule
      (PECAM)-1. In contrast, transcription was only modestly decreased in the DEX
      pretreated pigs compared to PZQ alone, and only for TNF-alpha, IL-6, IFN-gamma,
      TGF-beta and Ang1. IL-10 was not affected by either ETN or DEX pretreatments. The
      degree of inflammation, assessed by semi-quantitative inflammatory scores, was
      modestly decreased in both ETN and DEX pretreated animals compared to PZQ treated
      pigs whereas cyst damage scores were moderately decreased only in cysts from DEX
      pretreated pigs. However, the proportion of cysts with EB extravasation was not
      significantly changed in ETN and DEX pretreated groups. CONCLUSIONS/SIGNIFICANCE:
      Overall, TNF-alpha blockade using ETN treatment modulated expression of a large
      variety of genes that play a role in induction and control of inflammation and
      structural changes. In contrast the number of inflammatory cells was only
      moderately decreased suggesting weaker effects on cell migration into the
      inflammatory capsules surrounding cysts than on release of modulatory molecules.
      Taken together, these data suggest that TNF-alpha blockade may provide a viable
      strategy to manage post-treatment pericystic inflammation that follows
      antiparasitic therapy for neurocysticercosis.

PMID- 29190293
TI  - Morphological correlation between caloric tests and vestibular hydrops in
      Meniere's disease using intravenous Gd enhanced inner ear MRI.
AB  - The purpose of this study was to prove the hypothesis that caloric response in
      Meniere's disease (MD) is reduced by hydropic expansion of the vestibular
      labyrinth, not by vestibular hypofunction, by evaluating the correlation
      morphologically using an intravenous Gadolinium (IV-Gd) inner ear MRI. In study
      I, the prevalence of abnormal video Head Impulse Test (vHIT) results among the
      patients with definite unilateral MD (n = 24) and vestibular neuritis (VN) (n =
      22) were investigated. All patients showed abnormal canal paresis (CP) (> 26%) on
      caloric tests. The prevalence of abnormal vHIT in patients with abnormal CP was
      significantly lower in MD patients (12.5%) than that in VN patients (81.8%) (p <
      0.001). In study II, morphological correlation between caloric tests and
      vestibular hydrops level was evaluated in unilateral MD patients (n = 16) who had
      normal vHIT results. Eleven patients (61%) had abnormal CP. After taking the
      images of IV-Gd inner ear MRI, the vestibular hydrops ratio (endolymph
      volume/total lymph volume = %VH) was measured. In addition, the relative
      vestibular hydrops ratio (%RVH = (%VHaffected ear-%VHunaffected ear) /
      (%VHaffected ear + %VHunaffected ear)) was calculated. Each ratio (%VH and %RVH)
      was compared with average peak slow phase velocity (PSPV) and CP, respectively.
      In the MD patients, %VH of the affected ear correlated significantly with mean
      PSPV on the same side (rs = -0.569, p = 0.024), while %RVH correlated
      significantly with CP (rs = 0.602, p = 0.014). In most MD patients (87.5%)
      compared to VN patients, vHIT results were normal even though the caloric
      function was reduced. In addition, the reduced caloric function with normal vHIT
      was related to the severity of the vestibular hydrops measured by the IV-Gd inner
      ear MRI. These findings concluded that the abnormal caloric tests with normal
      vHIT in MD indicated severe endolymphatic hydrops rather than vestibular
      hypofunction.

PMID- 29190291
TI  - malERA: An updated research agenda for diagnostics, drugs, vaccines, and vector
      control in malaria elimination and eradication.
AB  - Since the turn of the century, a remarkable expansion has been achieved in the
      range and effectiveness of products and strategies available to prevent, treat,
      and control malaria, including advances in diagnostics, drugs, vaccines, and
      vector control. These advances have once again put malaria elimination on the
      agenda. However, it is clear that even with the means available today, malaria
      control and elimination pose a formidable challenge in many settings. Thus,
      currently available resources must be used more effectively, and new products and
      approaches likely to achieve these goals must be developed. This paper considers
      tools (both those available and others that may be required) to achieve and
      maintain malaria elimination. New diagnostics are needed to direct treatment and
      detect transmission potential; new drugs and vaccines to overcome existing
      resistance and protect against clinical and severe disease, as well as block
      transmission and prevent relapses; and new vector control measures to overcome
      insecticide resistance and more powerfully interrupt transmission. It is also
      essential that strategies for combining new and existing approaches are developed
      for different settings to maximise their longevity and effectiveness in areas
      with continuing transmission and receptivity. For areas where local elimination
      has been recently achieved, understanding which measures are needed to maintain
      elimination is necessary to prevent rebound and the reestablishment of
      transmission. This becomes increasingly important as more countries move towards
      elimination.

PMID- 29190294
TI  - CNGCs break through-A rice cyclic nucleotide-gated channel paves the way for
      pollen tube growth.

PMID- 29190296
TI  - Evaluating Bayesian spatial methods for modelling species distributions with
      clumped and restricted occurrence data.
AB  - Statistical approaches for inferring the spatial distribution of taxa (Species
      Distribution Models, SDMs) commonly rely on available occurrence data, which is
      often clumped and geographically restricted. Although available SDM methods
      address some of these factors, they could be more directly and accurately
      modelled using a spatially-explicit approach. Software to fit models with spatial
      autocorrelation parameters in SDMs are now widely available, but whether such
      approaches for inferring SDMs aid predictions compared to other methodologies is
      unknown. Here, within a simulated environment using 1000 generated species'
      ranges, we compared the performance of two commonly used non-spatial SDM methods
      (Maximum Entropy Modelling, MAXENT and boosted regression trees, BRT), to a
      spatial Bayesian SDM method (fitted using R-INLA), when the underlying data
      exhibit varying combinations of clumping and geographic restriction. Finally, we
      tested how any recommended methodological settings designed to account for
      spatially non-random patterns in the data impact inference. Spatial Bayesian SDM
      method was the most consistently accurate method, being in the top 2 most
      accurate methods in 7 out of 8 data sampling scenarios. Within high-coverage
      sample datasets, all methods performed fairly similarly. When sampling points
      were randomly spread, BRT had a 1-3% greater accuracy over the other methods and
      when samples were clumped, the spatial Bayesian SDM method had a 4%-8% better AUC
      score. Alternatively, when sampling points were restricted to a small section of
      the true range all methods were on average 10-12% less accurate, with greater
      variation among the methods. Model inference under the recommended settings to
      account for autocorrelation was not impacted by clumping or restriction of data,
      except for the complexity of the spatial regression term in the spatial Bayesian
      model. Methods, such as those made available by R-INLA, can be successfully used
      to account for spatial autocorrelation in an SDM context and, by taking account
      of random effects, produce outputs that can better elucidate the role of
      covariates in predicting species occurrence. Given that it is often unclear what
      the drivers are behind data clumping in an empirical occurrence dataset, or
      indeed how geographically restricted these data are, spatially-explicit Bayesian
      SDMs may be the better choice when modelling the spatial distribution of target
      species.

PMID- 29190297
TI  - "Up" or "down" that makes the difference. How giant honeybees (Apis dorsata) see
      the world.
AB  - A. dorsata builds its large exposed comb high in trees or under ledges of high
      rocks. The "open" nest of A. dorsata, shielded (only!) by multiple layers of
      bees, is highly vulnerable to any kind of direct contact or close range attacks
      from predators. Therefore, guard bees of the outer layer of A. dorsata's nest
      monitor the vicinity for possible hazards and an effective risk assessment is
      required. Guard bees, however, are frequently exposed to different objects like
      leaves, twigs and other tree litter passing the nest from above and falling to
      the ground. Thus, downward movement of objects past the nest might be used by A.
      dorsata to classify these visual stimuli near the nest as "harmless". To test the
      effect of movement direction on defensive responses, we used circular black discs
      that were moved down or up in front of colonies and recorded the number of guard
      bees flying towards the disc. The size of the disc (diameter from 8 cm to 50 cm)
      had an effect on the number of guard bees responding, the bigger the plate the
      more bees started from the nest. The direction of a disc's movement had a
      dramatic effect on the attraction. We found a significantly higher number of
      attacks, when discs were moved upwards compared to downward movements (GLMM
      (estimate +/- s.e.) 1.872 +/- 0.149, P < 0.001). Our results demonstrate for the
      first time that the vertical direction of movement of an object can be important
      for releasing defensive behaviour. Upward movement of dark objects near the
      colony might be an innate releaser of attack flights. At the same time, downward
      movement is perceived as a "harmless" stimulus.

PMID- 29190295
TI  - malERA: An updated research agenda for combination interventions and modelling in
      malaria elimination and eradication.
AB  - This paper summarises key advances and priorities since the 2011 presentation of
      the Malaria Eradication Research Agenda (malERA), with a focus on the
      combinations of intervention tools and strategies for elimination and their
      evaluation using modelling approaches. With an increasing number of countries
      embarking on malaria elimination programmes, national and local decisions to
      select combinations of tools and deployment strategies directed at malaria
      elimination must address rapidly changing transmission patterns across diverse
      geographic areas. However, not all of these approaches can be systematically
      evaluated in the field. Thus, there is potential for modelling to investigate
      appropriate 'packages' of combined interventions that include various forms of
      vector control, case management, surveillance, and population-based approaches
      for different settings, particularly at lower transmission levels. Modelling can
      help prioritise which intervention packages should be tested in field studies,
      suggest which intervention package should be used at a particular level or
      stratum of transmission intensity, estimate the risk of resurgence when scaling
      down specific interventions after local transmission is interrupted, and evaluate
      the risk and impact of parasite drug resistance and vector insecticide
      resistance. However, modelling intervention package deployment against a
      heterogeneous transmission background is a challenge. Further validation of
      malaria models should be pursued through an iterative process, whereby field data
      collected with the deployment of intervention packages is used to refine models
      and make them progressively more relevant for assessing and predicting
      elimination outcomes.

PMID- 29190298
TI  - The "F" in SAFE: Reliability of assessing clean faces for trachoma control in the
      field.
AB  - BACKGROUND: Although facial cleanliness is part of the SAFE strategy for trachoma
      there is controversy over the reliability of measuring a clean face. A child's
      face with no ocular and nasal discharge is clean and the endpoint of interest,
      regardless of the number of times it must be washed to achieve that endpoint. The
      issue of reliability rests on the reproducibility of graders to assess a clean
      face. We report the reproducibility of assessing a clean face in a field trial in
      Kongwa, Tanzania. METHODS/FINDINGS: Seven graders were trained to assess the
      presence and absence of nasal and ocular discharge on children's faces. Sixty
      children ages 1-7 years were recruited from a community and evaluated
      independently by seven graders, once and again about 50 minutes later. Intra-and
      inter-observer variation was calculated using unweighted kappa statistics. The
      average intra-observer agreement was kappa = 0.72, and the average inter-observer
      agreement was kappa = 0.78. CONCLUSIONS: Intra-observer and inter-observer
      agreement was substantial for the assessment of clean faces using trained
      Tanzania staff who represent a variety of educational backgrounds. As long as
      training is provided, the estimate of clean faces in children should be reliable,
      and reflect the effort of families to keep ocular and nasal discharge off the
      faces. These data suggest assessment of clean faces could be added to trachoma
      surveys, which already measure environmental improvements, in districts.

PMID- 29190299
TI  - A network diffusion approach to inferring sample-specific function reveals
      functional changes associated with breast cancer.
AB  - Guilt-by-association codifies the empirical observation that a gene's function is
      informed by its neighborhood in a biological network. This would imply that when
      a gene's network context is altered, for instance in disease condition, so could
      be the gene's function. Although context-specific changes in biological networks
      have been explored, the potential changes they may induce on the functional roles
      of genes are yet to be characterized. Here we analyze, for the first time, the
      network-induced potential functional changes in breast cancer. Using
      transcriptomic samples for 1047 breast tumors and 110 healthy breast tissues from
      TCGA, we derive sample-specific protein interaction networks and assign sample
      specific functions to genes via a diffusion strategy. Testing for significant
      changes in the inferred functions between normal and cancer samples, we find
      several functions to have significantly gained or lost genes in cancer, not due
      to differential expression of genes known to perform the function, but rather due
      to changes in the network topology. Our predicted functional changes are
      supported by mutational and copy number profiles in breast cancers. Our diffusion
      based functional assignment provides a novel characterization of a tumor that is
      complementary to the standard approach based on functional annotation alone.
      Importantly, this characterization is effective in predicting patient survival,
      as well as in predicting several known histopathological subtypes of breast
      cancer.

PMID- 29190300
TI  - malERA: An updated research agenda for malaria elimination and eradication.
AB  - Achieving a malaria-free world presents exciting scientific challenges as well as
      overwhelming health, equity, and economic benefits. WHO and countries are setting
      ambitious goals for reducing the burden and eliminating malaria through the
      "Global Technical Strategy" and 21 countries are aiming to eliminate malaria by
      2020. The commitment to achieve these targets should be celebrated. However, the
      need for innovation to achieve these goals, sustain elimination, and free the
      world of malaria is greater than ever. Over 180 experts across multiple
      disciplines are engaged in the Malaria Eradication Research Agenda (malERA)
      Refresh process to address problems that need to be solved. The result is a
      research and development agenda to accelerate malaria elimination and, in the
      longer term, transform the malaria community's ability to eradicate it globally.

PMID- 29190301
TI  - Identification and validation of reference genes for gene expression analysis in
      Aphidius gifuensis (Hymenoptera: Aphidiidae).
AB  - Reference genes have been utilized in estimating gene expression levels using
      quantitative reverse transcriptase-quantitative polymerase chain reaction (qRT
      PCR) analysis. Aphidius gifuensis Ashmaed is one of the most widely used
      biological control agents for aphids. The biological properties of this species
      have been studied in detail, and current investigations are focused on
      elucidating the regulatory mechanisms in its host However, the appropriate
      reference genes for target gene expression studies have not been identified. In
      this study, the expression profiles of 12 candidate reference genes were
      evaluated under different experimental conditions(development stage, sex, tissue
      type, diet) by using dedicated algorithms, including geNorm, Normfinder,
      BestKeeper, and DeltaCt. In addition, RefFinder was used to rank the overall
      stability of the candidate genes. Finally, we recommend three optimal reference
      genes for the normalization of qRT-PCR data in the presence of specific
      variables, which include ACTB, RPL13, and PPI for different developmental stages;
      RPS18, ACTB, and RPL13 for sexes; RPL13, PRII3, and RPS18 in different tissue
      types; and RPL13, RPL27, and ACTB in diverse diets. The present study has
      identified optimal reference genes that could be used in estimating the
      expression levels of specific genes under these conditions following the Minimum
      Information for publication of Quantitative real-time PCR Experiments (MIQE)
      guidelines, which would facilitate in advancements in functional genomics
      research on A. gifuensis.

PMID- 29190302
TI  - Light from dark: A relictual troglobite reveals a broader ancestral distribution
      for kimulid harvestmen (Opiliones: Laniatores: Kimulidae) in South America.
AB  - A new troglobitic harvestman, Relictopiolus galadriel gen. nov et sp. nov., is
      described from Olhos d'Agua cave, Itacarambi, Minas Gerais State, Brazil.
      Morphological characters, including male genitalia and exomorphology, suggest
      that this species belongs to the family Kimulidae, and it appears to share the
      greatest similarities with Tegipiolus pachypus. Bayesian inference analyses of a
      molecular dataset strongly support the inclusion of this species in Kimulidae and
      confirm the hypothesized sister-group relationship between R. galadriel and T.
      pachypus. A time calibrated phylogeny indicates that these sister-taxa diverged
      from a common ancestor approximately 40 Mya, during the Paleogene. The current
      range of Kimulidae illustrates a remarkable disjunct distribution, and leads us
      to hypothesize that the ancestral distribution of Kimulidae was once much more
      widespread across eastern Brazil. This may be attributed to the Eocene radiation
      associated with the warming (and humidifying) events in the Cenozoic when the
      best conditions for evergreen tropical vegetation in South America were
      established and followed by the extinction of kimulid epigean populations
      together with the retraction of rain forests during the Oligocene to Miocene
      cooling. The discovery of this relictual troglobite indicates that the Olhos
      d'Agua cave was a stable refugium for this ancient lineage of kimulids and acted
      as a "museum" of biodiversity. Our findings, considered collectively with the
      diverse troglofauna of the Olhos d'Agua cave, highlight it as one of the most
      important hotspots of troglobite diversity and endemism in the Neotropics. Given
      the ecological stresses on this habitat, the cavernicolous fauna are at risk of
      extinction and we emphasize the urgent need for appropriate conservation actions.
      Finally, we propose the transfer of Acanthominua, Euminua, Euminuoides and
      Pseudominua from Kimulidae to Zalmoxidae, resulting in two new synonymies and 13
      new combinations.

PMID- 29190303
TI  - Scabies in the age of increasing drug resistance.
AB  - Scabies is an infestation of the skin by the mite Sarcoptes scabiei. It manifests
      with pruritic erythematous papules and excoriations, in addition to the
      pathognomonic burrows. Multiple drugs can be used for treatment, but resistance
      to conventional therapy is increasing throughout the years. This paper will
      review the mechanisms of resistance proposed in the literature and some of the
      potential solutions to this problem.

PMID- 29190304
TI  - Letter to the Editor, The Authors Reply: "Cost and Utility of Thrombophilia
      Testing".
AB  - We thank Dr. Berse and colleagues for their correspondence about our paper. We
      are pleased they agreed with our conclusion: Thrombophilia testing has limited
      clinical utility in most inpatient settings.

PMID- 29190305
TI  - Letter to the Editor, What Can Be Done to Maintain Positive Patient Experience
      and Improve Residents' Satisfaction? In Reference to: "Standardized Attending
      Rounds to Improve the Patient Experience: A Pragmatic Cluster Randomized
      Controlled Trial".
AB  - We read the article by Monash et al. published in the March 2017 issue with great
      interest. This randomized study showed a discrepancy between patients' and
      residents' satisfaction with standardized rounds; for example, residents reported
      less autonomy, efficiency, teaching, and longer time of rounds.

PMID- 29190306
TI  - Letter to the Editor, The Authors Reply, "What Can Be Done to Maintain Positive
      Patient Experience and Improve Residents' Satisfaction?" and vStandardized
      Attending Rounds to Improve the Patient Experience: A Pragmatic Cluster
      Randomized Controlled Trial".
AB  - We thank Talrai et al. for their comments in response to our randomized
      controlled trial evaluating the impact of standardized rounds on patient,
      attending, and trainee satisfaction. We agree that many factors beyond rounding
      structure contribute to resident satisfaction, including those highlighted by the
      authors, and would enthusiastically welcome additional research in this realm.

PMID- 29190312
TI  - Cognitive and Neuropsychiatric Correlates of Functional Impairment Across the
      Continuum of No Cognitive Impairment to Dementia.
AB  - Objective: The ability to carry out instrumental activities (IADL) of daily
      living allows older adults to continue to live independently. Previous research
      suggested IADL were supported by multiple cognitive and neuropsychiatric factors.
      The primary goal of this study was to investigate whether immediate memory,
      executive functions, depression, and apathy, predicted unique variance in IADL
      over and above demographic variables (age and education) and general cognitive
      screening (Mini-Mental State Exam). Method: Participants (N = 403) were recruited
      from the Rural and Remote Memory Clinic (75 no cognitive impairment; 75 mild
      cognitive impairment; 139 dementia due to Alzheimer's disease; 114 non
      Alzheimer's dementia). Results: Results of hierarchical regression analyses
      suggested immediate memory, executive functions, apathy, and depression each
      accounted for unique variance in IADL in the overall sample, but as a predictor
      only apathy predicted variance in IADLs above demographics and general cognitive
      status. Further analysis of the diagnostic subgroups suggested different
      variables were more strongly associated with IADL from group to group (apathy and
      depression for normal participants, apathy for MCI participants and for
      participants with dementia due to AD, but not for those with non-AD dementia).
      Conclusions: The implications for developing cognitive rehabilitation
      interventions are discussed, with a recommendation for interventions for symptoms
      of apathy.

PMID- 29190313
TI  - TGF-beta signaling in cancer metastasis.
AB  - The transforming growth factor (TGF)-beta signaling events are well known to
      control diverse processes and numerous responses, such as cell proliferation,
      differentiation, apoptosis, and migration. TGF-beta signaling plays context
      dependent roles in cancer: in pre-malignant cells TGF-beta primarily functions as
      a tumor suppressor, while in the later stages of cancer TGF-beta signaling
      promotes invasion and metastasis. Recent studies have also suggested that the
      cross-talk between TGF-beta signaling and other signaling pathways, such as
      Hippo, Wnt, EGFR/RAS, and PI3K/AKT pathways, may substantially contribute to our
      current understanding of TGF-beta signaling and cancer. As a result of the wide
      ranging effects of TGF-beta, blockade of TGF-beta and its downstream signaling
      components provides multiple therapeutic opportunities. Therefore, the outlook
      for anti-TGF-beta signaling therapy for numerous diseases appears bright and will
      provide valuable information and thinking on the drug molecular design. In this
      review, we focus on recent insights into the regulation of TGF-beta signaling in
      cancer metastasis which may contribute to the development of novel cancer
      targeting therapies.

PMID- 29190315
TI  - Quantitative single-molecule study of TGF-beta/Smad signaling.
AB  - TGF-beta/Smad signaling pathway triggers diverse cellular responses among
      different cell types and environmental conditions. Quantitative analysis of
      protein-protein interactions involved in TGF-beta/Smad signaling is demanded for
      understanding the molecular mechanism of this signaling pathway. Live-cell single
      molecule microcopy with high spatiotemporal resolution is a new tool to monitor
      key molecular events in a real-time manner. In this review, we mainly presented
      the recent work on the quantitative characterization of TGF-beta/Smad signaling
      proteins by single-molecule method, and showed how it enabled us to obtain new
      insights about this canonical signaling process.

PMID- 29190316
TI  - Utility of initial induction chemotherapy with 5-fluorouracil, cisplatin, and
      docetaxel (DCF) for T4 esophageal cancer: a propensity score-matched analysis.
AB  - Although no consensus is available on the treatment of esophageal squamous cell
      carcinoma (ESCC) invading adjacent organs (T4), establishing effective induction
      treatments is crucial to altering an unresectable status and achieving curative
      resection. Here, we evaluated the efficacy of chemotherapy using 5-fluorouracil,
      cisplatin, and docetaxel (DCF) as the initial induction treatment for T4 ESCC.
      Fifty patients without distant metastasis who underwent initial induction
      chemotherapy using DCF for T4 ESCC were propensity score-matched with 50 patients
      who underwent radiotherapy concurrent with cisplatin and 5-fluorouracil (CRT). In
      the DCF group, 24 (48.0%) patients underwent surgery, achieving a 64% clinical
      response rate compared to 72.0% for induction CRT. CRT was also performed in
      another 24 (48.0%) patients in the DCF group in whom surgical resection was not
      indicated. The DCF group had significantly higher overall resectability than the
      CRT group (78.0% vs. 48.0%, P = 0.0017). The esophageal perforation rate during
      induction treatments was significantly lower in the DCF group than the CRT group
      (4.0% vs. 18.0%, P = 0.0205). Prognosis was significantly better in the DCF group
      than the CRT group (5-year cancer-specific survival 42.1% vs. 22.2%, P = 0.0146).
      Thus, induction DCF chemotherapy in patients with T4 ESCC reduced esophageal
      perforation and increased overall resectability, leading to better survival than
      CRT alone. Therefore, DCF chemotherapy may be an effective and safe option for
      initial induction treatment of T4 ESCC.

PMID- 29190317
TI  - TGF-beta signaling pathway in early mouse development and embryonic stem cells.
AB  - TGF-beta superfamily signaling pathways essentially contribute to the broad
      spectrum of early developmental events including embryonic patterning, cell fate
      determination and dynamic movements. In this review, we first introduced some key
      developmental processes that require TGF-beta signaling to show the fundamental
      importance of these pathways. Then we discuss how their activities are regulated,
      and new findings about how the TGF-beta superfamily ligands bind to the chromatin
      to regulate transcription during embryo development.

PMID- 29190314
TI  - The role of TGF-beta superfamily signaling in neurological disorders.
AB  - The TGF-beta superfamily signaling is involved in a variety of biological
      processes during embryogenesis and in adult tissue homeostasis. Faulty regulation
      of the signaling pathway that transduces the TGF-beta superfamily signals
      accordingly leads to a number of ailments, such as cancer and cardiovascular,
      metabolic, urinary, intestinal, skeletal, and immune diseases. In recent years, a
      number of studies have elucidated the essential roles of TGF-betas and BMPs
      during neuronal development in the maintenance of appropriate innervation and
      neuronal activity. The new advancement implicates significant roles of the
      aberrant TGF-beta superfamily signaling in the pathogenesis of neurological
      disorders. In this review, we compile a number of reports implicating the
      deregulation of TGF-beta/BMP signaling pathways in the pathogenesis of cognitive
      and neurodegenerative disorders in animal models and patients. We apologize in
      advance that the review falls short of providing details of the role of TGF
      beta/BMP signaling or mechanisms underlying the pathogenesis of neurological
      disorders. The goal of this article is to reveal a gap in our knowledge regarding
      the association between TGF-beta/BMP signaling pathways and neuronal tissue
      homeostasis and development and facilitate the research with a potential to
      develop new therapies for neurological ailments by modulating the pathways.

PMID- 29190318
TI  - Crosstalk between TGF-beta signaling and epigenome.
AB  - The transforming growth factor beta (TGF-beta) family of ligands plays major
      roles in embryonic development, tissue homeostasis, adult immunity, and wound
      repair. Dysregulation of TGF-beta signaling pathway leads to severe diseases. Its
      key components have been revealed over the past two decades. This family of
      cytokines acts by activating receptor activated SMAD (R-SMAD) transcription
      factors, which in turn modulate the expression of specific sets of target genes.
      Cells of a multicellular organism have the same genetic information, yet they
      show structural and functional differences owing to differential expression of
      their genes. Studies have demonstrated that epigenetic regulation, an integral
      part of the TGF-beta signaling, enables cells to sense and respond to TGF-beta
      signaling in a cell context-dependent manner. R-SMAD, as the central
      transcription factor of TGF-beta signaling, can recruit various epigenetic
      regulators to shape the transcriptome. In this review, we focus on epigenetic
      regulatory mechanisms in the TGF-beta signaling during mammalian development and
      diseases and discuss the central role of the interaction between R-SMAD and
      various epigenetic regulators in this epigenetic regulation. The crosstalk
      between TGF-beta signaling and the epigenome could serve as a versatile fine
      tuning mechanism for transcriptional regulation during embryonic development and
      progression of diseases, particularly cancer.

PMID- 29190321
TI  - Hypochlorous Acid Versus Povidone-Iodine Containing Irrigants: Which Antiseptic
      is More Effective for Breast Implant Pocket Irrigation?
AB  - Background: Capsular contracture induced by chronic subclinical infection is a
      major cause of poor outcomes and reoperation in breast implant surgery. The use
      of pocket irrigation with antiseptic/antibiotic has been shown to reduce the
      incidence of contracture. A new formulation of hypochlorous acid solution
      PhaseOne has been proposed as potential agent for irrigation. Objectives: This
      study aimed to test the efficacy of hypochlorous acid solution PhaseOne for use
      in breast pocket irrigation as an alternative to povidone iodine solution
      Betadine. Methods: The efficacy of PhaseOne, a hypochlorous acid formulated wound
      and skin cleanser, was tested in vitro against planktonic and biofilm
      Staphylococcus aureus with or without biological soil and in an implant
      attachment assay. Its activity was compared with Betadine containing 10% povidone
      iodine. Results: Our findings showed that PhaseOne was unable to eradicate
      planktonic and/or biofilm S. aureus in the presence of either tryptone soy broth
      or bovine calf serum (protein soil) in a variety of in vitro assays. Conclusions:
      We advise that povidone iodine containing irrigants are superior to hypochlorous
      acid containing irrigants in the clinical setting and should remain the
      recommended solution for pocket irrigation to reduce bacterial contamination at
      breast implants surgery.

PMID- 29190320
TI  - Comparing the Outcomes of Adults With Enterobacteriaceae Bacteremia Receiving
      Short-Course Versus Prolonged-Course Antibiotic Therapy in a Multicenter,
      Propensity Score-Matched Cohort.
AB  - Background: The recommended duration of antibiotic treatment for
      Enterobacteriaceae bloodstream infections is 7-14 days. We compared the outcomes
      of patients receiving short-course (6-10 days) vs prolonged-course (11-16 days)
      antibiotic therapy for Enterobacteriaceae bacteremia. Methods: A retrospective
      cohort study was conducted at 3 medical centers and included patients with
      monomicrobial Enterobacteriaceae bacteremia treated with in vitro active therapy
      in the range of 6-16 days between 2008 and 2014. 1:1 nearest neighbor propensity
      score matching without replacement was performed prior to regression analysis to
      estimate the risk of all-cause mortality within 30 days after the end of
      antibiotic treatment comparing patients in the 2 treatment groups. Secondary
      outcomes included recurrent bloodstream infections, Clostridium difficile
      infections (CDI), and the emergence of multidrug-resistant gram-negative (MDRGN)
      bacteria, all within 30 days after the end of antibiotic therapy. Results: There
      were 385 well-balanced matched pairs. The median duration of therapy in the short
      course group and prolonged-course group was 8 days (interquartile range [IQR], 7
      9 days) and 15 days (IQR, 13-15 days), respectively. No difference in mortality
      between the treatment groups was observed (adjusted hazard ratio [aHR], 1.00; 95%
      confidence interval [CI], .62-1.63). The odds of recurrent bloodstream infections
      and CDI were also similar. There was a trend toward a protective effect of short
      course antibiotic therapy on the emergence of MDRGN bacteria (odds ratio, 0.59;
      95% CI, .32-1.09; P = .09). Conclusions: Short courses of antibiotic therapy
      yield similar clinical outcomes as prolonged courses of antibiotic therapy for
      Enterobacteriaceae bacteremia, and may protect against subsequent MDRGN bacteria.

PMID- 29190319
TI  - Clinical consequences of upfront pathology review in the randomised PORTEC-3
      trial for high-risk endometrial cancer.
AB  - Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR
      EC) were randomised to receive pelvic radiotherapy (RT) with or without
      concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1
      and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175
      mg/m2). Pathology review was required before patient enrolment. The aim of this
      analysis was to evaluate the role of central pathology review before
      randomisation. Patients and methods: A total of 1295 cases underwent pathology
      review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and
      for 1226/1295 (95%) matching review and original reports were available. In
      total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the
      Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686
      participants. Areas of discrepancies were evaluated, and inter-observer agreement
      between original and review opinion was evaluated by calculating the kappa value
      (kappa). Results: In the 1226 pathology reviews, 6356 selected items were
      evaluable for both original and review pathology. In 43% of cases at least one
      pathology item changed after review. For 102 patients (8%), this discrepancy led
      to ineligibility for the PORTEC-3 trial, most frequently due to differences in
      the assessment of histological type (34%), endocervical stromal involvement (27%)
      and histological grade (19%). Lowest inter-observer agreement was found for
      histological type (kappa = 0.72), lymph-vascular space invasion (kappa = 0.72)
      and histological grade (kappa = 0.70). Conclusion: Central pathology review by
      expert gynaeco-pathologists changed histological type, grade or other items in
      43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%.
      Upfront pathology review is essential to ensure enrolment of the target trial
      population, and to avoid over- or undertreatment, especially when treatment
      modalities with substantial toxicity are involved. This study is registered with
      ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov
      (NCT00411138).

PMID- 29190322
TI  - Aesthetic Refinements in C-V Flap: Raising a Perfect Cylinder.

PMID- 29190323
TI  - A review of systemic anticancer therapy in disease palliation.
AB  - Background: Systemic anticancer therapy (SACT) is a collective term to describe
      the growing number of differing therapies used in malignancy to achieve
      palliation. Improving symptoms, quality of life (QOL) and where possible quantity
      of life are the goals of these treatments. Sources of data: A comprehensive
      literature review was undertaken using Medline, Embase and the Cochrane database.
      Areas of agreement: The use of palliative SACT can lead to increases in symptom
      control, QOL and survival. The breadth of treatable cancers has increased along
      with the number of therapeutic options. Areas of controversy: The increasing use
      of SACT in the last weeks of life and the lack of consistency about the terms
      Supportive Care/Best Supportive Care in the trial setting. Growing points:
      Integration between oncology and other palliative services leads to better
      outcomes. Areas timely for developing research: Improved prognostication tools to
      elucidate which patients will benefit from SACT.

PMID- 29190324
TI  - Enantioseparation of Substituted 1, 3-Diazaspiro [4.5]Decan-4-Ones: HPLC
      Comparative Study on Different Polysaccharide Type Chiral Stationary Phases.
AB  - Enantioseparation of substituted 1,3-diazaspiro[4.5]decan-4-ones (1-14) was
      achieved using different polysaccharide type chiral stationary phases (CSPs),
      namely, Chiralcel OJ, Chiralcel OD and Lux-Amylose-2 using different mobile
      phases which were either n-hexane/2-propanol or n-hexane/ethanol mixtures of
      various ratios (v/v) at flow rate 1 mL min-1. UV detection was carried out at 254
      nm and temperature of 20 degrees C. The retention behavior and selectivity of
      these CSPs were examined in isocratic normal phase high-performance liquid
      chromatography mode. The results revealed that the amylose CSP (Lux-Amylose-2)
      could separate almost all the compounds under investigation in contrast to
      cellulose CSPs (Chiracel OJ and Chiracel OD) which resolved fewer compounds.

PMID- 29190325
TI  - Joint Analysis of Cortical Area and Thickness as a Replacement for the Analysis
      of the Volume of the Cerebral Cortex.
AB  - Cortical surface area is an increasingly used brain morphology metric that is
      ontogenetically and phylogenetically distinct from cortical thickness and offers
      a separate index of neurodevelopment and disease. However, the various existing
      methods for assessment of cortical surface area from magnetic resonance images
      have never been systematically compared. We show that the surface area method
      implemented in FreeSurfer corresponds closely to the exact, but computationally
      more demanding, mass-conservative (pycnophylactic) method, provided that images
      are smoothed. Thus, the data produced by this method can be interpreted as
      estimates of cortical surface area, as opposed to areal expansion. In addition,
      focusing on the joint analysis of thickness and area, we compare an improved,
      analytic method for measuring cortical volume to a permutation-based
      nonparametric combination (NPC) method. We use the methods to analyze area,
      thickness and volume in young adults born preterm with very low birth weight, and
      show that NPC analysis is a more sensitive option for studying joint effects on
      area and thickness, giving equal weight to variation in both of these 2
      morphological features.

PMID- 29190326
TI  - Major Feedforward Thalamic Input Into Layer 4C of Primary Visual Cortex in
      Primate.
AB  - One of the underlying principles of how mammalian circuits are constructed is the
      relative influence of feedforward to recurrent synaptic drive. It has been dogma
      in sensory systems that the thalamic feedforward input is relatively weak and
      that there is a large amplification of the input signal by recurrent feedback.
      Here we show that in trichromatic primates there is a major feedforward input to
      layer 4C of primary visual cortex. Using a combination of 3D-electron-microscopy
      and 3D-confocal imaging of thalamic boutons we found that the average feedforward
      contribution was about 20% of the total excitatory input in the parvocellular (P)
      pathway, about 3 times the currently accepted values for primates. In the
      magnocellular (M) pathway it was around 15%, nearly twice the currently accepted
      values. New methods showed the total synaptic and cell densities were as much as
      150% of currently accepted values. The new estimates of contributions of
      feedforward synaptic inputs into visual cortex call for a major revision of the
      design of the canonical cortical circuit.

PMID- 29190327
TI  - Control of healthcare- and community-associated MRSA: recent progress and
      persisting challenges.
AB  - Background: Healthcare adapted meticillin-resistant Staphylococcus aureus (MRSA)
      has spread to hospitals around the world over 50 years. More recently, other
      strains of MRSA have emerged with the ability to spread in the community and
      infect otherwise healthy individuals. Morbidity and mortality associated with
      MRSA remains high and its control in both the healthcare and community setting
      has proven challenging. Sources of data: Pubmed (Medline). Areas of agreement:
      The use of targeted screening and decolonization, hand hygiene and antimicrobial
      stewardship is supported by the most robust studies, though many studies have
      implemented bundles for effective healthcare-associated (HA)-MRSA control. Areas
      of contention: Universal screening, universal decolonization and contact
      precautions for HA-MRSA control are supported by less evidence. Some
      interventions may not be cost-effective. Contact precautions may be associated
      with potential for patient harm. Evidence for effective control community
      acquired (CA)-MRSA is largely lacking. Growing points: Programmes that focus on
      implementing bundles of interventions aimed at targeting HA-MRSA are more likely
      to be effective, with an emphasis on hand hygiene as a key component. Control of
      CA-MRSA is likely to be more difficult to achieve and relies on prevalence, risk
      factors and community healthcare interactions on a broader scale. Areas timely
      for developing research: Further research in the area of CA-MRSA in particular is
      required. Antimicrobial stewardship for both CA and HA-MRSA is promising, as is
      the role of whole genome sequencing in characterizing transmission. However,
      further work is required to assess their long-term roles in controlling MRSA.
      With many institutions applying widespread use of chlorhexidine washes,
      monitoring for chlorhexidine resistance is paramount to sustaining efforts at
      controlling MRSA.

PMID- 29190329
TI  - Cortical Phase-Amplitude Coupling in a Progressive Model of Parkinsonism in
      Nonhuman Primates.
AB  - Parkinson's disease is associated with abnormal oscillatory electrical activities
      of neurons and neuronal ensembles throughout the basal ganglia-thalamocortical
      network. It has recently been documented in patients with advanced parkinsonism
      that the amplitude of gamma-band oscillations (50-200 Hz) in electrocorticogram
      recordings from the primary motor cortex is abnormally coupled to the phase of
      beta band oscillations within the same signals. It is not known when in the
      course of the disease the abnormal phase-amplitude coupling (PAC) arises, and
      whether it is influenced by arousal or prior exposure to dopaminergic
      medications. To address these issues, we analyzed the relationship between the
      severity of parkinsonian motor signs and the extent of PAC in a progressive model
      of parkinsonism, using primates that were not exposed to levodopa prior to
      testing. PAC was measured in electrocorticogram signals from the primary motor
      cortex and the supplementary motor area in 3 monkeys that underwent weekly
      injections of small doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine, rendering them progressively parkinsonian. We found that
      parkinsonism was associated with increased coupling between the phase of low
      frequency (4-10 Hz) oscillations and the amplitude of oscillations in the high
      gamma band (50-150 Hz). These changes only reached significance when the animals
      became fully parkinsonian. The increased PAC was normalized after levodopa
      treatment. We also found a similar increase in PAC during sleep, even in normal
      animals. The identified PAC was independent of concomitant changes in spectral
      power in the 2.9-9.8Hz or 49.8-150.4 Hz ranges. We conclude that PAC is
      predominately a sign of advanced parkinsonism, and is, thus, not essential for
      the development of parkinsonism. However, increased PAC appears to correlate with
      the severity of fully developed parkinsonism.

PMID- 29190328
TI  - The Computational Anatomy of Visual Neglect.
AB  - Visual neglect is a debilitating neuropsychological phenomenon that has many
      clinical implications and-in cognitive neuroscience-offers an important lesion
      deficit model. In this article, we describe a computational model of visual
      neglect based upon active inference. Our objective is to establish a
      computational and neurophysiological process theory that can be used to
      disambiguate among the various causes of this important syndrome; namely, a
      computational neuropsychology of visual neglect. We introduce a Bayes optimal
      model based upon Markov decision processes that reproduces the visual searches
      induced by the line cancellation task (used to characterize visual neglect at the
      bedside). We then consider 3 distinct ways in which the model could be lesioned
      to reproduce neuropsychological (visual search) deficits. Crucially, these 3
      levels of pathology map nicely onto the neuroanatomy of saccadic eye movements
      and the systems implicated in visual neglect.

PMID- 29190330
TI  - Human Cortical Thickness Organized into Genetically-determined Communities across
      Spatial Resolutions.
AB  - The cerebral cortex may be organized into anatomical genetic modules, communities
      of brain regions with shared genetic influences via pleiotropy. Such modules
      could represent novel phenotypes amenable to large-scale gene discovery. This
      modular structure was investigated with network analysis of in vivo MRI of
      extended pedigrees, revealing a "multiscale" structure where smaller and larger
      modules exist simultaneously and in partially overlapping fashion across spatial
      scales, in contrast to prior work suggesting a specific number of cortical
      thickness modules. Inter-regional genetic correlations, gene co-expression
      patterns and computational models indicate that two simple organizational
      principles account for a large proportion of the apparent complexity in the
      network of genetic correlations. First, regions are strongly genetically
      correlated with their homologs in the opposite cerebral hemisphere. Second,
      regions are strongly genetically correlated with nearby regions in the same
      hemisphere, with an initial steep decrease in genetic correlation with anatomical
      distance, followed by a more gradual decline. Understanding underlying
      organizational principles of genetic influence is a critical step towards a
      mechanistic model of how specific genes influence brain anatomy and mediate
      neuropsychiatric risk.

PMID- 29190331
TI  - Breast Erythema in a Patient With Breast Implant-Associated Anaplastic Large Cell
      Lymphoma: A Case Report Discussing Cutaneous Manifestations.
AB  - Level of Evidence 5: 

PMID- 29190332
TI  - The Neural Correlates of Intelligence Comparison.
AB  - Social comparison plays an important role in our daily life. Several studies have
      investigated the neural mechanism of social comparison; however, their
      conclusions remain controversial. The present study explored the neural
      correlates of intelligence comparison and nonsocial size comparison using
      functional magnetic resonance imaging and a distance effect paradigm. We found
      that both intelligence and size comparisons obeyed the behavioral distance effect
      longer response times for near than far distances and this effect involved an
      overlapping frontal network including the dorsomedial prefrontal cortex and
      insula. In addition, compared with size comparisons, intelligence comparisons
      elicited increased activity in the precuneus and angular gyrus, but decreased
      activity in the inferior parietal lobe. Furthermore, the analysis of seed-based
      functional connectivity complemented these neural commonalities and differences.
      Our findings suggest that social and nonsocial comparisons may rely on a common
      core mechanism, but this mechanism may be supplemented by different domain
      specific cognitive components.

PMID- 29190333
TI  - Determination of Sophorabioside in Rat Plasma by UPLC-MS/MS and its Application
      to a Pharmacokinetic Study.
AB  - A ultra-performance liquid chromatography tandem mass spectrometry method was
      initially developed and validated for quantification of sophorabioside in rat
      plasma using kaempferol-3-O-beta-D-rutinoside as the internal standard (IS).
      Analyte and IS were preparation through a protein precipitation procedure with
      1.0 mL of methanol to a 0.1 mL plasma sample. The processed samples were
      separated by C18 analytical column using methanol/water containing 0.1% formic
      acid with gradient elution as the mobile phase at a flow rate of 0.3 mL/min.
      Sophorabioside (m/z 577.15 -> 269.45) and kaempferol-3-O-beta-D-rutinoside (m/z
      593.15 -> 285.84) were detected by a triple quadrupole tandem mass spectrometer
      in negative electrospray ionization mode using multiple reaction monitoring. The
      calibration curve for sophorabioside was linear in the range of 6-1,200 ng/mL (r2
      > 0.995) with a lower limit of quantification of 6 ng/mL. The inter- and intra
      day precision and accuracy were well within the acceptable limits. The matrix
      effects were satisfactory in all of the biological matrices examined. The mean
      recovery of sophorabioside was always >90%. This method was successfully applied
      to a pharmacokinetic study of sophorabioside in rats after an oral administration
      of 90 mg/kg sophorabioside. The main pharmacokinetic parameters: Tmax, Cmax and
      t1/2 were 6.2 +/- 0.8 h, 1430.83 +/- 183.25 ng/mL, 7.2 +/- 0.5 h, respectively.

PMID- 29190334
TI  - The Ventral Posterior Lateral Thalamus Preferentially Encodes Externally Applied
      Versus Active Movement: Implications for Self-Motion Perception.
AB  - Successful interaction with our environment requires that voluntary behaviors be
      precisely coordinated with our perception of self-motion. The vestibular sensors
      in the inner ear detect self-motion and in turn send projections via the
      vestibular nuclei to multiple cortical areas through 2 principal thalamocortical
      pathways, 1 anterior and 1 posterior. While the anterior pathway has been
      extensively studied, the role of the posterior pathway is not well understood.
      Accordingly, here we recorded responses from individual neurons in the ventral
      posterior lateral thalamus of macaque monkeys during externally applied (passive)
      and actively generated self-motion. The sensory responses of neurons that
      robustly encoded passive rotations and translations were canceled during
      comparable voluntary movement (~80% reduction). Moreover, when both passive and
      active self-motion were experienced simultaneously, neurons selectively encoded
      the detailed time course of the passive component. To examine the mechanism
      underlying the selective elimination of vestibular sensitivity to active motion,
      we experimentally controlled correspondence between intended and actual head
      movement. We found that suppression only occurred if the actual sensory
      consequences of motion matched the motor-based expectation. Together, our
      findings demonstrate that the posterior thalamocortical vestibular pathway
      selectively encodes unexpected motion, thereby providing a neural correlate for
      ensuring perceptual stability during active versus externally generated motion.

PMID- 29190335
TI  - Examination of the Construct Validity of the Repeatable Battery for the
      Assessment of Neuropsychological Status Language Index in a Mixed Neurological
      Sample.
AB  - Objective: We sought to examine the construct validity of the Language Index of
      the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
      Methods: Archival neuropsychological data were collected for 2,057 individuals of
      diverse neurological etiologies. Results: Correlations were seen between the
      RBANS Language Index and its indices (Semantic Fluency r = .727; Picture Naming r
      = .786), between Semantic Fluency and both Category Fluency (r = .379) and the
      Controlled Oral Word Association test (r = .375), and between Picture Naming and
      both Visual Naming from the Multilingual Aphasia Examination (r = .447) and the
      Boston Naming Test (r = .519). Finally, Picture Naming predicted performance on
      both Visual Naming [F(1,495) = 123.36, p < .000] and the Boston Naming Test
      [F(1,262) = 96.28, p < .000]. Conclusion: Given these results, support for the
      interpretation of RBANS Language Index appears warranted in a diverse clinical
      sample.

PMID- 29190336
TI  - Slow Waves in Cortical Slices: How Spontaneous Activity is Shaped by Laminar
      Structure.
AB  - Cortical slow oscillations (SO) of neural activity spontaneously emerge and
      propagate during deep sleep and anesthesia and are also expressed in isolated
      brain slices and cortical slabs. We lack full understanding of how SO integrate
      the different structural levels underlying local excitability of cell assemblies
      and their mutual interaction. Here, we focus on ongoing slow waves (SWs) in
      cortical slices reconstructed from a 16-electrode array designed to probe the
      neuronal activity at multiple spatial scales. In spite of the variable
      propagation patterns observed, we reproducibly found a smooth strip of loci
      leading the SW fronts, overlapping cortical layers 4 and 5, along which Up states
      were the longest and displayed the highest firing rate. Propagation modes were
      uncorrelated in time, signaling a memoryless generation of SWs. All these
      features could be modeled by a multimodular large-scale network of spiking
      neurons with a specific balance between local and intermodular connectivity.
      Modules work as relaxation oscillators with a weakly stable Down state and a peak
      of local excitability to model layers 4 and 5. These conditions allow for both
      optimal sensitivity to the network structure and richness of propagation modes,
      both of which are potential substrates for dynamic flexibility in more general
      contexts.

PMID- 29190338
TI  - Erratum to: Dr Mary Norine Walsh, President of ACC: As the new President of the
      American College of Cardiology (ACC), Dr Mary N. Walsh explains how she hopes her
      election will help advance new opportunities for women in the field.

PMID- 29190339
TI  - Corrigendum to: Monocyte and haematopoietic progenitor reprogramming as common
      mechanism underlying chronic inflammatory and cardiovascular diseases.

PMID- 29190337
TI  - Optimizing Research to Speed Up Availability of Pediatric Antiretroviral Drugs
      and Formulations.
AB  - Globally 1.8 million children are living with human immunodeficiency virus (HIV),
      yet only 51% of those eligible actually start treatment. Research and development
      (R&D) for pediatric antiretrovirals (ARVs) is a lengthy process and lags
      considerably behind drug development in adults. Providing safe, effective, and
      well-tolerated drugs for children remains critical to ensuring scale-up globally.
      We review current approaches to R&D for pediatric ARVs and suggest innovations to
      enable simplified, faster, and more comprehensive strategies to develop optimal
      formulations. Several approaches could be adopted, including focusing on a
      limited number of prioritized formulations and strengthening existing
      partnerships to ensure that pediatric investigation plans are developed early in
      the drug development process. Simplified and more efficient mechanisms to
      undertake R&D need to be put in place, and financing mechanisms must be made more
      sustainable. Lessons learned from HIV should be shared to support progress in
      developing pediatric formulations for other diseases, including tuberculosis and
      viral hepatitis.

PMID- 29190341
TI  - Oral Health Care Needs of Young Adults Transitioning from Foster Care.
AB  - Children who have aged out of the foster care system face considerable barriers
      in accessing oral health care. Although this population of foster care alumni may
      have Medicaid insurance while they are in care to cover dental care, 39 percent
      of youths who have aged out of foster care do not have dental insurance. This
      mixed methods study examines factors that contribute to the oral health care
      disparities of children who have transitioned from foster care. Multivariate
      analysis revealed that foster care alumni without dental insurance are 93.5
      percent less likely to have their dental needs met than those with dental
      insurance. Themes from the qualitative data indicated a lack of oral health care,
      quality-of-life issues, and lack of support to access ongoing dental care. Most
      state Medicaid programs do not provide comprehensive dental care for adults past
      the age of 20, contributing to oral health disparities among this population. The
      addition of oral health care coverage under the Patient Protection and Affordable
      Health Care Act of 2010 for foster care alumni would greatly enhance their
      quality of life. The article concludes with a discussion of the implications for
      the role of social workers in promoting oral health care for foster care youths.

PMID- 29190340
TI  - Continuous Glucose Monitoring for Hypoglycemia Avoidance and Glucose
      Counterregulation in Long-Standing Type 1 Diabetes.
AB  - Context: Patients with long-standing type 1 diabetes (T1D) are at increased risk
      for severe hypoglycemia because of defects in glucose counterregulation and
      recognition of hypoglycemia symptoms, in part mediated through exposure to
      hypoglycemia. Objective: To determine whether implementation of real-time
      continuous glucose monitoring (CGM) as a strategy for hypoglycemia avoidance
      could improve glucose counterregulation in patients with long-standing T1D and
      hypoglycemia unawareness. Design, Setting, Participants, and Intervention: Eleven
      patients with T1D disease duration of ~31 years were studied longitudinally in
      the Clinical & Translational Research Center of the University of Pennsylvania
      before and 6 and 18 months after initiation of CGM and were compared with 12
      nondiabetic control participants. Main Outcome Measure: Endogenous glucose
      production response derived from paired hyperinsulinemic stepped-hypoglycemic and
      euglycemic clamps with infusion of 6,6-2H2-glucose. Results: In patients with
      T1D, hypoglycemia awareness (Clarke score) and severity (HYPO score and severe
      events) improved (P < 0.01 for all) without change in hemoglobin A1c (baseline,
      7.2% +/- 0.2%). In response to insulin-induced hypoglycemia, endogenous glucose
      production did not change from before to 6 months (0.42 +/- 0.08 vs 0.54 +/- 0.07
      mg.kg-1.min-1) but improved after 18 months (0.84 +/- 0.15 mg.kg-1.min-1; P <
      0.05 vs before CGM), albeit remaining less than in controls (1.39 +/- 0.11 mg.kg
      1.min-1; P <= 0.01 vs all). Conclusions: Real-time CGM can improve awareness and
      reduce the burden of problematic hypoglycemia in patients with long-standing T1D,
      but with only modest improvement in the endogenous glucose production response
      that is required to prevent or correct low blood glucose.

PMID- 29190342
TI  - Social Workers and Mobile Child Crisis Screening.

PMID- 29190343
TI  - Thanks, Steve!

PMID- 29190344
TI  - Response of Maize Hybrids With and Without Rootworm- and Drought-Tolerance to
      Rootworm Infestation Under Well-Watered and Drought Conditions.
AB  - Anecdotal data in the past have suggested that the effect of the western corn
      rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), on
      maize yield is greater under drought and the effect of drought is greater under
      rootworm infestations, but no field experiments have controlled both moisture and
      rootworm levels. Field studies were conducted in 2012, 2013, and 2014 with
      treatments in a factorial arrangement of western corn rootworm infestation
      levels, and maize hybrids (with and without tolerance to drought and rootworm
      feeding). The experiment was repeated under well-watered and drought conditions
      in adjacent plots. Leaf water potential and stomatal conductance data suggested
      significant plant stress was achieved in the drought plots toward the end of the
      season each year and maize hybrids only played a minor role. In particular, in
      2012 and 2013 yield was dramatically lower for the drought experiment than for
      the well-watered experiment. However, the impacts of rootworm infestation level
      and maize hybrids on water potential, stomatal conductance, and yield were
      variable across years and between experiments. In fact, the only year that the
      main effect of rootworm infestation levels significantly impacted yield was in
      2014, when an extremely high infestation level was added and this was only for
      the well-watered portion of the experiment. Overall, rootworm infestation level
      played a relatively minor role in maize productivity and it did not appear that
      soil moisture level influenced that to a large degree.

PMID- 29190345
TI  - Data Resource Profile: The Nordic Obesity Surgery Cohort (NordOSCo).

PMID- 29190346
TI  - Broad support for regulating the clinical implementation of future reproductive
      techniques.
AB  - STUDY QUESTION: Do gynaecologists, infertile patients and the general public,
      consider that regulation of the clinical implementation of stem cell-based
      fertility treatments is required? SUMMARY ANSWER: There is broad support from
      gynaecologists, patients and the general public for regulating the clinical
      implementation of future stem cell-based fertility treatments. WHAT IS KNOWN
      ALREADY: There is debate on the need to regulate the clinical implementation of
      novel techniques. Regulation may hinder their swift adoption and delay benefits
      for patients, but may prevent the implementation of ineffective or harmful
      techniques. Stem cell-based fertility treatments, which involve creating oocytes
      or spermatozoa by manipulating stem cells, are likely to be implemented in
      clinical practice in the near future and will probably impact future generations
      as well as the current one. STUDY DESIGN, SIZE, DURATION: A cross-sectional
      survey was conducted among gynaecologists working in fertility clinics (n = 179),
      patients with severe infertility (n = 348) and a representative sample of the
      general public (n = 1250). The questionnaire was disseminated in the Netherlands
      in the winter of 2015-2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The newly
      developed questionnaire was reviewed by experts and tested among the general
      public. The questionnaire assessed whether participants wanted each of nine
      potential negative consequences of the clinical implementation of stem cell-based
      fertility treatments to be regulated. In addition, the importance of all negative
      and positive potential consequences, the appropriate regulatory body and its need
      to consult with advisors from various backgrounds was questioned. MAIN RESULTS
      AND THE ROLE OF CHANCE: In total, 958 respondents completed the questionnaire
      (response rate: 54%). A large majority of each participant group (>85%) wanted
      regulation, for at least one potential negative consequence of the clinical
      implementation of stem cell-based fertility treatments. The majority of all
      participant groups wanted regulation for serious health risks for intended
      parents, serious health risks for children and the disposal of human embryos.
      Regulation for out-of-pocket costs and the burden of treatment received little
      support. The majority of gynaecologists and the general public, but not the
      patients, requested regulation for the risk of minor congenital abnormalities,
      the success rates and the naturalness of treatments. Nevertheless, the majority
      of patients did consider the former two potential negative consequences
      important. The majority of all groups preferred a national bioethics committee as
      the regulatory body. This committee should consult with advisors from various
      backgrounds and should consider the broader context of potential consequences of
      the stem cell-based fertility treatments. LIMITATIONS, REASONS FOR CAUTION: This
      empirical study focuses on only three stakeholder groups. This study reports on
      the perspective of the majority and this is not per definition the morally right
      perspective. The transferability of our findings to other cultures and other
      techniques remains unclear. WIDER IMPLICATIONS OF THE FINDINGS: A national
      bioethics committee, consulting with advisors from various backgrounds, should
      regulate the clinical implementation of future stem cell-based fertility
      treatments. Whether this broad support for regulation applies to novel techniques
      from other fields of medicine should be examined. STUDY FUNDING/COMPETING
      INTEREST(S): The Young Academy of the Royal Netherlands Academy of Arts and
      Sciences. None of the authors has any conflict of interest to declare. TRIAL
      REGISTRATION NUMBER: Not applicable.

PMID- 29190348
TI  - Computational fluid dynamics study of the end-side and sequential coronary artery
      bypass anastomoses in a native coronary occlusion model.
AB  - OBJECTIVES: The objective of this study was to evaluate the haemodynamic patterns
      in each anastomosis fashion using a computational fluid dynamic study in a native
      coronary occlusion model. METHODS: Fluid dynamic computations were carried out
      with ANSYS CFX (ANSYS Inc., Canonsburg, PA, USA) software. The incision lengths
      for parallel and diamond anastomoses were fixed at 2 mm. Native vessels were set
      to be totally occluded. The diameter of both the native and graft vessels was set
      to be 2 mm. The inlet boundary condition was set by a sample of the transient
      time flow measurement which was measured intraoperatively. RESULTS: The diamond
      anastomosis was observed to reduce flow to the native outlet and increase flow to
      the bypass outlet; the opposite was observed in the parallel anastomosis. Total
      energy efficiency was higher in the diamond anastomosis than the parallel
      anastomosis. Wall shear stress was higher in the diamond anastomosis than in the
      parallel anastomosis; it was the highest at the top of the outlet. A high
      oscillatory shear index was observed at the bypass inlet in the parallel
      anastomosis and at the native inlet in the diamond anastomosis. CONCLUSIONS: The
      diamond sequential anastomosis would be an effective option for multiple
      sequential bypasses because of the better flow to the bypass outlet than with the
      parallel anastomosis. However, flow competition should be kept in mind while
      using the diamond anastomosis for moderately stenotic vessels because of worsened
      flow to the native outlet. Care should be taken to ensure that the fluid dynamics
      patterns are optimal and prevent future native and bypass vessel disease
      progression.

PMID- 29190347
TI  - ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus
      associated haemorrhagic cystitis in haematopoietic stem cell transplant
      recipients.
AB  - Objectives: To define guidelines for BK polyomavirus (BKPyV)-associated
      haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. Methods: Review
      of English literature and evidence-based recommendations by expert consensus.
      Results: BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients
      undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro
      haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other
      relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific
      semiquantitative follow-up marker. No randomized controlled trials are available
      to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or
      bladder irrigation showed limited prophylactic value. Fluoroquinolones are not
      effective for prophylaxis or treatment, but rather increase antibiotic
      resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on
      small case series from correspondingly equipped centres. Although cidofovir has
      been reported to improve and/or reduce BKPyV viraemia or viruria, the current
      data do not support its regular use. Conclusions: BKPyV-HC remains a disabling
      unmet clinical need in HSCT that requires novel approaches supported by proper
      clinical trials.

PMID- 29190351
TI  - The associations of thiopurines with male fertility and paternally exposed
      offspring: a systematic review and meta-analysis.
AB  - BACKGROUND: Thiopurines are widely used immunosuppressive agents. In high
      dosages, they inhibit the purine synthesis and are considered to be possibly
      harmful to spermatogenesis, and subsequently to men's fertility and their
      offspring. However, the clear association between thiopurine exposure and male
      fertility and reproduction safety, if any, is still poorly understood. OBJECTIVE
      AND RATIONALE: The aim of this review was to systematically summarize and meta
      analyse the available data, derived from animal and human studies, regarding the
      influence of thiopurine exposure on fertility and conception safety in men and
      their offspring. SEARCH METHODS: A systematic literature search of the MEDLINE
      and EMBASE databases was performed using a combination of relevant terms related
      to 'thiopurines', 'fertility', 'conception', 'reproduction', 'semen quality' and
      'birth outcome', combined with 'male', 'men', 'father' and 'paternal'. The search
      was not restricted exclusively to human subjects, neither to a type of disease or
      condition, to gather all available studies with regards to this topic. All
      published articles on thiopurines and male fertility, written in English and
      published until May 2017, were screened for eligibility. The GRADE guidelines
      were used to assess the quality of evidence of the included articles. OUTCOMES: A
      total of 28 studies (including 14 observational studies in humans) were included
      in this review and six of these were included in the meta-analysis. In various
      rodents, thiopurines adversely affected the germ cells (in administered doses of
      2 to 20 times the human equivalent dose). In human studies, thiopurine therapy
      was not evidently associated with impaired testicular function or semen quality
      in 83 men with a variety of underlying diseases. In total, 53 out of 975
      offspring with congenital anomalies (5.4%, the background prevalence is 3%),
      possibly as a result of paternal thiopurine exposure, were described in all
      studies together. The risk of congenital anomalies was not significantly
      increased when compared with offspring without paternal thiopurine exposure
      (4.7%) (pooled odds ratio 1.32, 95% confidence interval 0.75, 2.34). WIDER
      IMPLICATIONS: Thiopurines have spermatotoxic effects in rodents. In humans,
      overall data are limited and derived from underpowered studies, and therefore not
      conclusive with regards to the possible effects of thiopurines on spermatogenesis
      or paternally exposed offspring. Larger, epidemiological trials evaluating the
      safety of thiopurines to men's fertility and their offspring are mandatory to
      adequately counsel thiopurine treated men who wish to conceive.

PMID- 29190350
TI  - Psychometric analysis of the TRANSIT quality indicators for cardiovascular
      disease prevention in primary care.
AB  - Objective: To assess a selection of psychometric properties of the TRANSIT
      indicators. Design: Using medical records, indicators were documented
      retrospectively during the 14 months preceding the end of the TRANSIT study.
      Setting: Primary care in Quebec, Canada. Participants: Indicators were documented
      in a random subsample (n = 123 patients) of the TRANSIT study population (n =
      759). Interventions: For every patient, the mean compliance to all indicators of
      a category (subscale score) and to the complete set of indicators (overall scale
      score) were established. To evaluate test-retest and inter-rater reliabilities,
      indicators were applied twice, two months apart, by the same evaluator and
      independently by different evaluators, respectively. To evaluate convergent
      validity, correlations between TRANSIT indicators, Burge et al. indicators and
      Institut national d'excellence en sante et en services sociaux (INESSS)
      indicators were examined. Main Outcome Measures: Test-retest reliability, inter
      rater reliability, and convergent validity. Results: Test-retest reliability, as
      measured by intraclass correlation coefficients (ICCs) was equal to 0.99 (0.99
      0.99) for the overall scale score while inter-rater reliability was equal to 0.95
      (0.93-0.97) for the overall scale score. Convergent validity, as measured by
      Pearson's correlation coefficients, was equal to 0.77 (P < 0.001) for the overall
      scale score when the TRANSIT indicators were compared to Burge et al. indicators
      and to 0.82 (P < 0.001) for the overall scale score when the TRANSIT indicators
      were compared to INESSS indicators. Conclusions: Reliability was excellent except
      for eleven indicators while convergent validity was strong except for domains
      related to the management of CVD risk factors.

PMID- 29190349
TI  - Identification and characterization of the Streptococcus pneumoniae type 3
      capsule-specific glycoside hydrolase of Paenibacillus species 32352.
AB  - Bacillus circulans Jordan 32352 was isolated from decaying organic matter in the
      New Jersey soil in the early 1930s. This soil-dwelling bacterium produced an
      enzyme capable of degrading the type 3 capsular polysaccharide (Pn3P) of
      Streptococcus pneumoniae (Spn). Early reports of this enzyme, Pn3Pase,
      demonstrated its inducibility by, and specificity for Pn3P. We set out to
      identify and clone this enzyme for its recombinant expression and
      characterization. We first sequenced the genome of this bacterial species, and
      reclassified the Pn3Pase producing bacterium as Paenibacillus species 32352. We
      identified the putative protein of Pn3Pase through mass spectrometry-based
      proteomics and cloned the gene for recombinant expression. We then characterized
      the oligosaccharide products generated upon the enzymatic depolymerization of
      Pn3P. Sequence analysis suggests that this glycoside hydrolase belongs to a new
      carbohydrate-active enzyme GH family. To our knowledge, this is the only enzyme
      to demonstrate Pn3P depolymerization activity.

PMID- 29190352
TI  - Clinical outcomes and prognostic factors of chemoradiotherapy for postoperative
      lymph node recurrence of esophageal cancer.
AB  - Background: The therapeutic strategies and prognostic risk factors in patients
      with lymph node (LN) recurrence of esophageal cancer remain controversial. We
      assessed clinical outcomes and prognostic factors related to the use of
      chemoradiotherapy (CRT) for LN recurrence of esophageal squamous cell carcinoma
      (ESCC) after curative resection. Methods: We retrospectively evaluated survival
      and prognostic factors in 57 patients with LN recurrence of ESCC after curative
      resection. Patients received CRT using 5-fluorouracil plus cisplatin (FP) or
      docetaxel. Radiotherapy was delivered at 2 Gy (total dose, 60-66 Gy; median, 60
      Gy). Results: The median follow-up duration was 24 (range, 3-116) months. The
      overall survival (OS) rates at 2, 3 and 5 years were 43.7%, 36.9% and 27.6%,
      respectively. In the univariate analysis of OS, treatment with FP, a single LN
      recurrence, and a single regional recurrence were associated with a significantly
      better prognosis (P = 0.04, P = 0.027 and P = 0.0001, respectively). In the
      multivariate analysis, the combination chemotherapy regimen [hazard ratio (HR),
      2.50; 95% confidence interval (CI), 1.23-5.07] and the number of the regional LNs
      with recurrence (HR, 5.76; 95% CI, 1.22-27.12) were independent prognostic
      factors. Conclusion: Approximately 28% of ESCC patients with LN recurrence after
      curative resection could achieve long-term survival with CRT. Treatment with FP
      or patients with a single regional recurrence might improve the treatment
      outcome.

PMID- 29190353
TI  - Is the scaling relationship between carbohydrate storage and leaf biomass in
      meadow plants affected by the disturbance regime?
AB  - Background and Aims: Below-ground carbohydrate storage is considered an
      adaptation of plants aimed at regeneration after disturbance. A theoretical model
      by Iwasa and Kubo was empirically tested which predicted (1) that storage of
      carbohydrates scales allometrically with leaf biomass and (2) when the
      disturbance regime is relaxed, the ratio of storage to leaf biomass increases, as
      carbohydrates are not depleted by disturbance. Methods: These ideas were tested
      on nine herbaceous species from a temperate meadow and the disturbance regime was
      manipulated to create recently abandoned and mown plots. Just before mowing in
      June and at the end of the season in October, plants with below-ground organs
      were sampled. The material was used to assess the pool of total non-structural
      carbohydrates and leaf biomass. Key Results: In half of the cases, a mostly
      isometric relationship between below-ground carbohydrate storage and leaf biomass
      in meadow plants was found. The ratio of below-ground carbohydrate storage to
      leaf biomass did not change when the disturbance regime was less intensive than
      that for which the plants were adapted. Conclusions: These findings (isometric
      scaling relationship between below-ground carbohydrate storage and leaf biomass;
      no effect of a relaxed disturbance regime) imply that storage in herbs is
      probably governed by factors other than just the disturbance regime applied once
      in a growing season.

PMID- 29190354
TI  - Plant Cuttings: news in Botany.

PMID- 29190355
TI  - Trends in practice and outcomes from 2011 to 2015 for surgical aortic valve
      replacement: an update from the German Aortic Valve Registry on 42 776 patients.
AB  - OBJECTIVES: Surgical aortic valve replacement (sAVR) is coming under close
      scrutiny with the recent upswing in the use of less invasive approaches. The aim
      of this analysis was to identify current trends in patient selection, procedural
      characteristics and outcomes after sAVR in Germany. METHODS: We analysed data
      from 42 776 patients included in the German Aortic Valve Registry who underwent
      sAVR with and without coronary artery bypass surgery (CABG) between 2011 and
      2015. Baseline, procedural and short-term outcome parameters were analysed.
      RESULTS: Of all registered patients, 26 618 (62.2%) underwent isolated sAVR and
      16 158 (37.8%) sAVR + CABG. The median age was 72 years, and the median Society
      of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) was 2.3%. From 2011
      to 2015, there was a decline in STS PROM (2.4-2.2%, P < 0.001) and a decline in
      risk factors, such as pulmonary hypertension (9.1-3.2%, P < 0.001), occlusive
      arterial disease (19.6-17.7%, P = 0.003), mitral regurgitation >=2 degrees  (10.6
      7.6%, P < 0.001) and New York Heart Association Class III/IV (65.3-59.2%, P <
      0.001). In-hospital mortality was 2.3%, 1.3% had disabling stroke, 0.4% residual
      aortic regurgitation >=2 degrees , and the incidence of new-onset
      pacemaker/implantable cardioverter-defibrillator implantation was 3.9%. There was
      an increase in the use of biological valves in patients <65 years (50.1-65.7%, P
      < 0.001), and the proportion of rapid deployment valves increased significantly
      (1.5-8.4%, P < 0.001) over the investigated time period. CONCLUSIONS: Both
      isolated sAVR as well as sAVR + CABG resulted in excellent in-hospital outcomes
      based on >42 000 patients treated between 2011 and 2015. The implementation of
      alternative treatment strategies has resulted in palpable changes in patient and
      device selection.

PMID- 29190356
TI  - Multimodality imaging of a right atrial blood cyst.

PMID- 29190357
TI  - The Tele.TAnDem Intervention: Telephone-based CBT for Family Caregivers of People
      With Dementia.
AB  - Background and Objectives: This study evaluated the effectiveness of a telephone
      based cognitive-behavioral therapy for family caregivers of people with dementia
      in existing health care provision structures. Research Design and Methods: Two
      hundred seventy-three family caregivers of people with dementia were randomly
      assigned to receive the intervention or usual care. Usual care included
      unrestricted access to community resources. Intervention group participants
      received twelve 50-min sessions of individual cognitive-behavioral therapy by
      trained psychotherapists within 6 months. Symptoms of depression, emotional well
      being, physical health symptoms, burden of care, coping with the care situation
      and challenging behavior were assessed after the intervention ended and at a 6
      month follow-up. Intention-to-treat analyses using latent change models were
      applied. Results: Intention-to-treat analyses showed improved emotional well
      being (gamma = 9.59, p = .001), fewer symptoms of depression (gamma = -0.23, p =
      .043), fewer physical health symptoms (gamma = -0.25, p = .019), improved coping
      with the care situation (gamma = 0.25, p = .005) and the behavior of the care
      recipient (gamma = 0.23, p = .034) compared with usual care. Effects for coping
      (gamma = 0.28, p = .006 and gamma = 0.39, p < .001, respectively) and emotional
      well-being (gamma = 7.61, p = .007) were also found at follow-up. Discussion and
      Implications: The CBT-based telephone intervention increased mental and physical
      health as well as coping abilities of family caregivers of people with dementia.
      The intervention can be delivered by qualified CBT therapists after an 8-h
      training session in existing health care provision structures.

PMID- 29190358
TI  - Developmental Connectivity and Molecular Phenotypes of Unique Cortical Projection
      Neurons that Express a Synapse-Associated Receptor Tyrosine Kinase.
AB  - The complex circuitry and cell-type diversity of the cerebral cortex are required
      for its high-level functions. The mechanisms underlying the diversification of
      cortical neurons during prenatal development have received substantial attention,
      but understanding of neuronal heterogeneity is more limited during later periods
      of cortical circuit maturation. To address this knowledge gap, connectivity
      analysis and molecular phenotyping of cortical neuron subtypes that express the
      developing synapse-enriched MET receptor tyrosine kinase were performed.
      Experiments used a MetGFP transgenic mouse line, combined with coexpression
      analysis of class-specific molecular markers and retrograde connectivity mapping.
      The results reveal that MET is expressed by a minor subset of subcerebral and a
      larger number of intratelencephalic projection neurons. Remarkably, MET is
      excluded from most layer 6 corticothalamic neurons. These findings are
      particularly relevant for understanding the maturation of discrete cortical
      circuits, given converging evidence that MET influences dendritic elaboration and
      glutamatergic synapse maturation. The data suggest that classically defined
      cortical projection classes can be further subdivided based on molecular
      characteristics that likely influence synaptic maturation and circuit wiring.
      Additionally, given that MET is classified as a high confidence autism risk gene,
      the data suggest that projection neuron subpopulations may be differentially
      vulnerable to disorder-associated genetic variation.

PMID- 29190360
TI  - Barriers to Transition From Pediatric to Adult Care: A Systematic Review.
AB  - Objective: Transition research in each disease group is developing in its own
      "silo." A comprehensive review of barriers to transition within and across
      chronic illness groups is needed to facilitate information sharing and larger
      scale efforts to overcome barriers and improve patient care. This study
      systematically reviews and identifies the barriers to transition from pediatric
      to adult care across pediatric illness populations. Methods: Medline, CINAHL,
      PsychINFO, Social Services Abstracts, Web of Science, and the Cochrane library
      databases were searched. Peer-reviewed English articles presenting original data
      on barriers to transition to adult care, focused on a specific pediatric chronic
      illness population, and conducted in the United States were included. Study
      design, population, and barriers were extracted. Barriers were categorized
      according to the Socioecological Model of Adolescent/Young Adult Readiness to
      Transition. Articles were evaluated for study quality. Results: Fifty-seven
      articles were included. The most common barriers to transition fell within the
      "Relationships" domain (e.g., difficulties letting go of long-standing
      relationships with pediatric providers) followed by "Access/Insurance" (e.g.,
      difficulty accessing/finding qualified practitioners, insurance issues), and
      "Beliefs/Expectations" (e.g., negative beliefs about adult care). Barriers
      related to "Knowledge" (e.g., limited patient/caregiver knowledge about
      medication/illness and the transition process) and "Skills/Efficacy" (e.g., lack
      of self-management skills) were also common. While relationship barriers were
      commonly reported by all, some barriers varied by transfer status (pre- vs.
      posttransfer). Conclusions: Each chronic illness group experiences illness
      specific challenges but certain barriers transcend chronic illness populations.
      Suggestions to overcome these barriers are provided.

PMID- 29190359
TI  - DNA terminal structure-mediated enzymatic reaction for ultra-sensitive
      discrimination of single nucleotide variations in circulating cell-free DNA.
AB  - Sensitive detection of the single nucleotide variants in cell-free DNA (cfDNA)
      may provide great opportunity for minimally invasive diagnosis and prognosis of
      cancer and other related diseases. Here, we demonstrate a facile new strategy for
      quantitative measurement of cfDNA mutations at low abundance in the cancer
      patients' plasma samples. The method takes advantage of a novel property of
      lambda exonuclease which effectively digests a 5'-fluorophore modified dsDNA with
      a 2-nt overhang structure and sensitively responds to the presence of mismatched
      base pairs in the duplex. It achieves a limit of detection as low as 0.02%
      (percentage of the mutant type) for BRAFV600E mutation, NRASQ61R mutation and
      three types of EGFR mutations (G719S, T790M and L858R). The method enabled
      identification of BRAFV600E and EGFRL858R mutations in the plasma of different
      cancer patients within only 3.5 h. Moreover, the terminal structure-dependent
      reaction greatly simplifies the probe design and reduces the cost, and the assay
      only requires a regular real-time PCR machine. This new method may serve as a
      practical tool for quantitative measurement of low-abundance mutations in
      clinical samples for providing genetic mutation information with prognostic or
      therapeutic implications.

PMID- 29190361
TI  - Shaping epigenetic memory via genomic bookmarking.
AB  - Reconciling the stability of epigenetic patterns with the rapid turnover of
      histone modifications and their adaptability to external stimuli is an
      outstanding challenge. Here, we propose a new biophysical mechanism that can
      establish and maintain robust yet plastic epigenetic domains via genomic
      bookmarking (GBM). We model chromatin as a recolourable polymer whose segments
      bear non-permanent histone marks (or colours) which can be modified by 'writer'
      proteins. The three-dimensional chromatin organisation is mediated by protein
      bridges, or 'readers', such as Polycomb Repressive Complexes and Transcription
      Factors. The coupling between readers and writers drives spreading of biochemical
      marks and sustains the memory of local chromatin states across replication and
      mitosis. In contrast, GBM-targeted perturbations destabilise the epigenetic
      patterns. Strikingly, we demonstrate that GBM alone can explain the full
      distribution of Polycomb marks in a whole Drosophila chromosome. We finally
      suggest that our model provides a starting point for an understanding of the
      biophysics of cellular differentiation and reprogramming.

PMID- 29190363
TI  - Efficient in situ barcode sequencing using padlock probe-based BaristaSeq.
AB  - Cellular DNA/RNA tags (barcodes) allow for multiplexed cell lineage tracing and
      neuronal projection mapping with cellular resolution. Conventional approaches to
      reading out cellular barcodes trade off spatial resolution with throughput. Bulk
      sequencing achieves high throughput but sacrifices spatial resolution, whereas
      manual cell picking has low throughput. In situ sequencing could potentially
      achieve both high spatial resolution and high throughput, but current in situ
      sequencing techniques are inefficient at reading out cellular barcodes. Here we
      describe BaristaSeq, an optimization of a targeted, padlock probe-based technique
      for in situ barcode sequencing compatible with Illumina sequencing chemistry.
      BaristaSeq results in a five-fold increase in amplification efficiency, with a
      sequencing accuracy of at least 97%. BaristaSeq could be used for barcode
      assisted lineage tracing, and to map long-range neuronal projections.

PMID- 29190362
TI  - A human prefrontal-subthalamic circuit for cognitive control.
AB  - The subthalamic nucleus is a key site controlling motor function in humans. Deep
      brain stimulation of the subthalamic nucleus can improve movements in patients
      with Parkinson's disease; however, for unclear reasons, it can also have
      cognitive effects. Here, we show that the human subthalamic nucleus is
      monosynaptically connected with cognitive brain areas such as the prefrontal
      cortex. Single neurons and field potentials in the subthalamic nucleus are
      modulated during cognitive processing and are coherent with 4-Hz oscillations in
      medial prefrontal cortex. These data predict that low-frequency deep brain
      stimulation may alleviate cognitive deficits in Parkinson's disease patients. In
      line with this idea, we found that novel 4-Hz deep brain stimulation of the
      subthalamic nucleus improved cognitive performance. These data support a role for
      the human hyperdirect pathway in cognitive control, which could have relevance
      for brain-stimulation therapies aimed at cognitive symptoms of human brain
      disease.awx300media15660002226001.

PMID- 29190364
TI  - Development of the MapMe intervention body image scales of known weight status
      for 4-5 and 10-11 year old children.
AB  - Background: Parents tend to visually assess children to determine their weight
      status and typically underestimate child body size. A visual tool may aid parents
      to more accurately assess child weight status and so support strategies to reduce
      childhood overweight. Body image scales (BIS) are visual images of people ranging
      from underweight to overweight but none exist for children based on UK criteria.
      Our aim was to develop sex- and age-specific BIS for children, based on British
      growth reference (UK90) criteria. Methods: BIS were developed using 3D surface
      body scans of children, their associated weight status using UK90 criteria from
      height and weight measurements, and qualitative work with parents and health
      professionals. Results: Height, weight and 3D body scans were collected (211: 4-5
      years; 177: 10-11 years). Overall, 12 qualitative sessions were held with 37
      participants. Four BIS (4-5-year-old girls and boys, 10-11-year-old girls and
      boys) were developed. Conclusions: This study has created the first sex- and age
      specific BIS, based on UK90 criteria. The BIS have potential for use in child
      overweight prevention and management strategies, and in future research. This
      study also provides a protocol for the development of further BIS appropriate to
      other age groups and ethnicities.

PMID- 29190365
TI  - A National Portrait of Stepfamilies in Later Life.
AB  - Objectives: Scholars have documented increases in the prevalence and complexity
      of stepfamilies earlier in the life course, but no one has systematically
      investigated U.S. stepfamily structure in later life. Guided by a family systems
      approach, we described the prevalence and composition of later-life stepfamilies.
      Method: The analysis was based on 6,250 married and cohabiting couples
      participating in the 2012 Health and Retirement Study. We identified the
      prevalence of later-life stepfamilies, decomposed stepfamily structures, and
      compared the sociodemographic characteristics and relationship quality of the
      couples in stepfamilies with those in married families (with only joint children
      and no stepchildren), paying attention to differences between married and
      cohabiting stepfamilies. Results: Roughly 40% of middle-aged and older couples
      with children were in stepfamilies. Of all stepfamilies, 86% were married couples
      and 14% were cohabiting couples. Cohabiting stepfamilies more often included
      children from both partners' previous relationships, but couples in married
      stepfamilies more often had joint children. Cohabiting stepfamilies appeared to
      be the most socially and economically disadvantaged, followed by married
      stepfamilies, and lastly married families. Despite these compositional
      differences, partner relationship quality was largely similar across married
      families, married stepfamilies, and cohabiting stepfamilies. Discussion: This
      study underscores the high prevalence and complexity of later-life stepfamilies
      and foregrounds the urgency of additional research on this topic.

PMID- 29190366
TI  - Unexpected drought resistance strategies in seedlings of four Brachychiton
      species.
AB  - Functional traits associated with drought resistance can be useful for predicting
      tree responses to a drying climate. Yet drought resistance is likely achieved
      through a complex combination of constitutive traits (traits expressed even in
      benign environments) and plastic traits (traits expressed only in response to
      drought). Because few studies measure multiple traits for multiple species under
      both well-watered and drought conditions, we often struggle to identify suites of
      constitutive and plastic traits indicative of drought resistance strategies.
      Using a greenhouse experiment, we examined nine drought resistance traits (six
      morphological/allocation traits plus assimilation, stomatal conductance and water
      use efficiency) in well-watered and water-stressed seedlings of four Brachychiton
      (Malvaceae Juss.) species with ranges spanning a strong aridity gradient in east
      central Australia. In benign conditions, constitutive biomass allocation was
      consistent with expectations, with xeric species investing more heavily in roots
      and stem tissue and less in leaf tissue than mesic species (P = 0.004). Under
      drought conditions, xeric species decreased relative biomass allocation below
      ground while mesic species increased relative below-ground allocation (treatment
      * species interaction P = 0.0015). Relative water content of the stems was
      slightly higher in xeric species (P = 0.055), and remained stable during drought
      while decreasing in mesic species (treatment * species P = 0.001). Specific leaf
      area (SLA) and leaf dry matter content (LDMC) did not fit with expectations under
      either benign or water-limited conditions. Moreover, stomatal conductance and
      carbon assimilation were unexpectedly highest and intrinsic water-use efficiency
      (WUEi) lowest in the xeric species in benign conditions. Only under drought did
      the xeric species manifest higher WUEi than the mesic species (treatment *
      species P < 0.0001). We found that even closely related species exhibited diverse
      combinations of drought resistance traits. Notably, traits commonly used as
      proxies for drought tolerance (e.g., SLA, LDMC, well-watered WUEi) performed more
      poorly than constitutive allocation traits. This study highlights the need to
      consider multiple traits and phenotypic plasticity when assessing species'
      drought resistance for forest management in the face of climate change.

PMID- 29190367
TI  - Early Experience with Bilateral Continuous Femoral Nerve Block and Single
      Injection Spinal Anesthesia for Bilateral Total Knee Arthroplasty: A Case Series.
AB  - Objective: Total knee arthroplasty (TKA) is a commonly performed surgery in the
      United States, with demand for unilateral and simultaneous bilateral TKAs (BTKAs)
      expected to increase significantly over the coming decades. This study reports
      the authors' early experience in a consecutive series of simultaneous BTKAs
      performed under regional anesthesia and mild sedation. Methods: In this
      retrospective case series, the authors examined all simultaneous BTKAs performed
      over two years by a single surgeon. Only patients receiving bilateral continuous
      femoral nerve blockade (CFNB) and single-injection sciatic nerve blockade in
      combination with single-injection subarachnoid block were included in the study.
      Of the 32 patients who underwent BTKAs during this period, 25 met the inclusion
      criteria. The patient's anesthesia records, physician notes, nursing notes,
      pharmacy records, and physical therapy records were then reviewed systematically
      to create a database of information. Results: Only one of 25 patients required
      conversion to general anesthesia during surgery. There were no major
      perioperative complications. The average Defense and Veterans Pain Rating Scale
      score immediately postoperation was 0.6/10, and the average daily score remained
      below 3.5/10 throughout the hospital stay. The use of bilateral CFNB did not
      prevent patients from ambulating during physiotherapy. Conclusions: This early
      retrospective case series suggests that it is feasible to effectively manage the
      postoperative pain associated with BTKA with staged bilateral CFNB and single
      injection sciatic nerve blockage in combination with single-injection
      subarachnoid block as the sole anesthetic technique without negatively
      influencing early ambulation.

PMID- 29190368
TI  - Interindividual variability in gut microbiota and host response to dietary
      interventions.
AB  - Dysbiosis is linked to human disease; therefore, gut microbiota modulation
      strategies provide an attractive means of correcting microbial imbalance to
      enhance human health. Because diet has a major influence on the composition,
      diversity, and metabolic capacity of the gut microbiota, numerous dietary
      intervention studies have been conducted to manipulate the gut microbiota to
      improve host outcomes and reduce disease risk. Emerging evidence suggests that
      interindividual variability in gut microbiota and host responsiveness exists,
      making it difficult to predict gut microbiota and host response to a given
      dietary intervention. This may, in turn, have implications on the consistency of
      results among studies and the perceived success or true efficacy of a dietary
      intervention in eliciting beneficial changes to the gut microbiota and human
      health.

PMID- 29190369
TI  - Decision-Making Preferences and Deprescribing: Perspectives of Older Adults and
      Companions About Their Medicines.
AB  - Objectives: Polypharmacy in the older population is increasing-and can be
      harmful. It can be safe to reduce or carefully cease medicines (deprescribing)
      but a collaborative approach between patient and doctor is required. This study
      explores decision-making about polypharmacy with older adults and their
      companions. Method: Semi-structured interviews were conducted with 30 older
      people (aged 75+ years, taking multiple medicines) and 15 companions. Framework
      analysis was used to identify qualitative themes. Results: Participants varied
      considerably in attitudes towards medicines, preferences for involvement in
      decision-making, and openness to deprescribing. Three types were identified. Type
      1 held positive attitudes towards medicines, and preferred to leave decisions to
      their doctor. Type 2 voiced ambivalent attitudes towards medicines, preferred a
      proactive role, and were open to deprescribing. Type 3 were frail, perceived they
      lacked knowledge about medicines, and deferred most decisions to their doctor or
      companion. Discussion: This study provides a novel typology to describe
      differences between older people who are happy to take multiple medicines, and
      those who are open to deprescribing. To enable shared decision-making,
      prescribers need to adapt their communication about polypharmacy based on their
      patients' attitudes to medicines and preferences for involvement in decisions.

PMID- 29190370
TI  - Best practices for using natural experiments to evaluate retail food and beverage
      policies and interventions.
AB  - Policy and programmatic change in the food retail setting, including excise taxes
      on beverages with added-caloric sweeteners, new supermarkets in food deserts, and
      voluntary corporate pledges, often require the use of natural experimental
      evaluation for impact evaluation when randomized controlled trials are not
      possible. Although natural experimental studies in the food retail setting
      provide important opportunities to test how nonrandomized interventions affect
      behavioral and health outcomes, researchers face several key challenges to
      maintaining strong internal and external validity when conducting these studies.
      Broadly, these challenges include 1) study design and analysis; 2) selection of
      participants, selection of measures, and obtainment of data; and 3) real-world
      considerations. This article addresses these challenges and different approaches
      to meeting them. Case studies are used to illustrate these approaches and to
      highlight advantages and disadvantages of each approach. If the trade-offs
      required to address these challenges are carefully considered, thoughtful natural
      experimental evaluations can minimize bias and provide critical information about
      the impacts of food retail interventions to a variety of stakeholders, including
      the affected population, policymakers, and food retailers.

PMID- 29190371
TI  - Determination of Cephalosporins by UHPLC-DAD Using Molecularly Imprinted
      Polymers.
AB  - Molecularly imprinted polymers (MIPs) were synthesized for the determination of
      cephalosporins (cephazolin, ceftazidime, cefotaxime, ceftriaxone, cefepime and
      cephalexin) by ultra-high performance liquid chromatography with diode-array
      detection (UHPLC-DAD). After optimization, MIPs were synthesized using cephazolin
      as the template, methacrylic acid as the functional monomer, triethylenglycol
      dimethacrylate as the crosslinker, acetonitrile/dimethylsulfoxide as porogens and
      benzoyl peroxide as the radical initiator. Not only this is a novel route of MIP
      synthesis for cephalosporins, but also this choice of analytes is unique.
      Chromatographic separation was performed in a C8 column using a binary gradient
      with trifluoroacetic acid 0.1% in water and acetonitrile. Linearity was assessed
      up to 100 MUg mL-1 and linear correlation coefficients (r) were all higher than
      0.99, limits of detection were within the range of 3-12 ng mL-1, and recoveries
      from 86 to 102% were obtained for concentrations between 0.05 and 1.0 MUg mL-1.

PMID- 29190372
TI  - What Can Elder Mistreatment Researchers Learn About Primary Prevention From
      Family Violence Intervention Models?
AB  - Elder mistreatment (EM) is a public health problem that harms millions of older
      Americans each year. Despite growing recognition of its occurrence, there are no
      evidence-based primary prevention programs. Although EM is distinct from other
      areas of family violence, including child maltreatment and intimate partner
      violence, common risk factors and theoretical underpinnings point to
      opportunities for prevention strategies. Drawing on evidence-based best practices
      found in other fields of family violence, we identify approaches that could be
      tested to prevent EM at the hands of family caregivers, who are among the most
      likely to commit mistreatment. Specifically, we examine home visiting approaches
      primarily used in the child maltreatment field and identify components that have
      potential to inform EM interventions, including prevention. We conclude that
      there is enough information to begin testing a prevention intervention for EM
      that targets caregivers.

PMID- 29190373
TI  - Adult and elderly population access to trauma centers: an ecological analysis
      evaluating the relationship between injury-related mortality and geographic
      proximity in the United States in 2010.
AB  - Background: Ongoing development and expansion of trauma centers in the United
      States necessitates empirical analysis of the effect of investment in such
      resources on population-level health outcomes. Methods: Multiple linear
      regressions were performed to predict state-level trauma-related mortality among
      adults and the elderly across 50 US states in 2010. The number of trauma centers
      per capita in each state and the percentage of each state's population living
      within 45-min of a trauma center served as the key independent variables and
      injury-related mortality served as the dependent variable. All analyses were
      stratified by age (adult versus elderly; elderly >= 65 years old) and were
      performed in SPSS. Results: The proportion of a population with geographic
      proximity to a trauma center demonstrates a consistent inverse linear
      relationship to injury-related mortality. The relationship reliably retains its
      significance in models including demographic covariates. Interestingly, access to
      Levels I and II trauma centers demonstrates a stronger correlation with mortality
      than was observed with Level III centers. Conclusion: Trauma center access is
      associated with reduced trauma-related mortality among both adults and the
      elderly as measured by state reported mortality rates. Ongoing efforts to
      designate and verify new trauma centers, particularly in poorly-served 'trauma
      deserts', could lead to lower mortality for large populations.

PMID- 29190374
TI  - Scaling up newborn care in Afghanistan: opportunities and challenges for the
      health sector.
AB  - Newborn health in Afghanistan is receiving increased attention, but reduction in
      newborn deaths there has not kept pace with declines in maternal and child
      mortality. Using the continuum of care and health systems building block
      frameworks, this article identifies, organizes and provides a synthesis of the
      available evidence on and gaps in coverage of care and health systems,
      programmes, policies and practices related to newborn health in Afghanistan.
      Newborn mortality in Afghanistan is related to the nation's weak health system,
      itself associated with decades of conflict, low and uneven coverage of essential
      interventions, demand-side and cultural specificities, and compromised quality. A
      majority of deliveries still take place at home. Birth asphyxia, low birth
      weight, perinatal infections and poor post-natal care are responsible for many
      preventable newborn deaths. Though the situation has improved, there remain many
      opportunities to accelerate progress. Analyses conducted using the Lives Saved
      Tools suggest that an additional 10 405 newborn lives could be saved in
      Afghanistan in 5 years (2015-20), through reasonable increases in coverage of
      these high-impact interventions. A long-term vision and strong leadership are
      essential for the Ministry of Public Health to play an effective stewardship role
      in formulating related policy and strategy, setting standards and monitoring
      maternal and newborn services. Promotion of equitable access to health services,
      including health workforce planning, development and management, and the
      coordination of much-needed donor support are also imperative.

PMID- 29190375
TI  - High-resolution mapping of molecules in an ionic liquid via scanning transmission
      electron microscopy.
AB  - Understanding structures and spatial distributions of molecules in liquid phases
      is crucial for the control of liquid properties and to develop efficient liquid
      phase processes. Here, real-space mapping of molecular distributions in a liquid
      was performed. Specifically, the ionic liquid 1-Ethyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide (C2mimTFSI) was imaged using atomic-resolution
      scanning transmission electron microscopy. Simulations revealed network-like
      bright regions in the images that were attributed to the TFSI- anion, with
      minimal contributions from the C2mim+ cation. Simple visualization of the TFSI-
      distribution in the liquid sample was achieved by binarizing the experimental
      image.

PMID- 29190376
TI  - p53 promotes AKT and SP1-dependent metabolism through the pentose phosphate
      pathway that inhibits apoptosis in response to Nutlin-3a.
AB  - Nutlin-3a is a MDM2 antagonist and preclinical drug that activates p53. Cells
      with MDM2 gene amplification are especially prone to Nutlin-3a-induced apoptosis,
      though the basis for this is unclear. Glucose metabolism can inhibit apoptosis in
      response to Nutlin-3a through mechanisms that are incompletely understood.
      Glucose metabolism through the pentose phosphate pathway (PPP) produces NADPH
      that can protect cells from potentially lethal reactive oxygen species (ROS). We
      compared apoptosis and glucose metabolism in cancer cells with and without MDM2
      gene amplification treated with Nutlin-3a. Apoptosis in MDM2-amplified cells was
      associated with a reduction in glycolysis and the PPP, reduced NADPH, increased
      ROS, and depletion of the transcription factor SP1, which normally promotes PPP
      gene expression. In contrast, glycolysis and the PPP were maintained or increased
      in MDM2 non-amplified cells treated with Nutlin-3a. This was dependent on p53
      mediated AKT activation and was associated with maintenance of SP1 and continued
      expression of PPP genes. Knockdown or inhibition of AKT, SP1, or the PPP
      sensitized MDM2-non-amplified cells to apoptosis. The data indicate that p53
      promotes AKT and SP1-dependent activation of the PPP that protects cells from
      Nutlin-3a-induced apoptosis. These findings provide insight into how glucose
      metabolism reduces Nutlin-3a-induced apoptosis, and also provide a mechanism for
      the heightened sensitivity of MDM2-amplified cells to apoptosis in response to
      Nutlin-3a.

PMID- 29190378
TI  - Bilingual Text With or Without Pictograms Improves Elderly Singaporeans'
      Understanding of Prescription Medication Labels.
AB  - Background and Objectives: In Singapore, primarily English-language prescription
      medication labels challenge elderly Singaporeans, many of whom are unable to read
      English. We investigated whether bilingual text and pictograms can help them
      understand prescription medication labels. Research Design and Methods: We
      randomized 1,414 elderly respondents of a national survey into four prescription
      medication labels: English-text; English-text-and-pictograms; Bilingual-text; and
      Bilingual-text-and-pictograms, which were similar except for the addition of
      another language and/or pictograms (International Pharmaceutical Federation,
      FIP). Respondents answered 16 label-related questions; an expert panel rated
      answers for correctness. Outcomes were (1) complete understanding (16 correct);
      (2) any understanding (>=1 correct); and (3) number of incorrect answers among
      those with any understanding. We evaluated associations of each prescription
      medication label (vs. English-text) with outcomes (1), (2), and (3) using
      logistic and negative binomial regression, respectively. Results: The elderly
      respondents were similar across the four prescription medication labels (English
      text, English-text-and-pictograms, Bilingual-text, Bilingual-text-and
      pictograms), for which the proportions with outcomes (1) and (2) were (17.9%,
      25.6%, 36.9%, 40.1%) and (50.4%, 62.6%, 75.9%, 76.5%), respectively. We observed
      statistically significant higher odds of outcomes (1) and (2) among those
      assigned the three labels (vs. English-text): English-text-and-pictograms, 1.96
      and 2.51; Bilingual-text, 3.54 and 6.73; and Bilingual-text-and-pictograms, 4.51
      and 7.93. Those assigned the three labels also had 0.94, 1.98, and 2.12 fewer
      outcome (3) on average (vs. English-text). Discussion and Implications: Adding
      bilingual text with or without pictograms on prescription medication labels
      considerably improved elderly Singaporeans' understanding of the labels, strongly
      suggesting its application in practice. Other issues in prescription medication
      labels design and content, including adapting FIP pictograms for elderly
      Singaporeans, warrant further investigation.

PMID- 29190379
TI  - Fungal-specific Cyp51 inhibitor VT-1598 demonstrates in vitro activity against
      Candida and Cryptococcus species, endemic fungi, including Coccidioides species,
      Aspergillus species and Rhizopus arrhizus.
AB  - Background: Invasive fungal infections, including those caused by yeasts, moulds
      and endemic organisms, can be significant causes of morbidity and mortality in
      immunocompromised hosts, those with multiple comorbidities and occasionally
      immunocompetent hosts. Current antifungal agents are often limited by drug
      toxicities, drug interactions or the development of resistance. VT-1598 is a
      novel tetrazole that has greater specificity for fungal Cyp51 than currently
      available triazoles and thus the potential for clinically significant drug
      interactions is reduced. We measured the in vitro activity of VT-1598 against
      clinical isolates of Candida and Cryptococcus species, endemic fungi, including
      Coccidioides, Blastomyces and Histoplasma, Aspergillus species and Rhizopus
      arrhizus. Methods: Antifungal susceptibility testing was performed by broth
      microdilution or macrodilution methods per CLSI standards. Clinical isolates of
      each species were used and clinically available antifungal agents were tested
      against each isolate. Results: VT-1598 demonstrated in vitro activity against
      yeasts and moulds that was similar to or greater than that of clinically
      available antifungal agents, including amphotericin B, fluconazole, caspofungin,
      voriconazole and posaconazole. The in vitro activity of VT-1598 was also
      maintained against resistant isolates, including fluconazole-resistant Candida
      isolates. In vitro activity was also observed against endemic fungi, including
      Blastomyces, Histoplasma and both Coccidioides immitis and Coccidioides
      posadasii. Conclusions: VT-1598 demonstrated in vitro activity against yeasts,
      moulds and endemic fungi, which was maintained against isolates that had reduced
      susceptibility to other antifungals. Further studies are warranted to evaluate
      the in vivo efficacy of VT-1598 against various fungal pathogens.

PMID- 29190377
TI  - European Society of Cardiology: Cardiovascular Disease Statistics 2017.
AB  - Aims: The European Society of Cardiology (ESC) Atlas has been compiled by the
      European Heart Agency to document cardiovascular disease (CVD) statistics of the
      56 ESC member countries. A major aim of this 2017 data presentation has been to
      compare high-income and middle-income ESC member countries to identify
      inequalities in disease burden, outcomes, and service provision. Methods and
      results: The Atlas utilizes a variety of data sources, including the World Health
      Organization, the Institute for Health Metrics and Evaluation, and the World Bank
      to document risk factors, prevalence, and mortality of cardiovascular disease and
      national economic indicators. It also includes novel ESC-sponsored survey data of
      health infrastructure and cardiovascular service provision provided by the
      national societies of the ESC member countries. Data presentation is descriptive
      with no attempt to attach statistical significance to differences observed in
      stratified analyses. Important differences were identified between the high
      income and middle-income member countries of the ESC with regard to CVD risk
      factors, disease incidence, and mortality. For both women and men, the age
      standardized prevalence of hypertension was lower in high-income countries (18%
      and 27%) compared with middle-income countries (24% and 30%). Smoking prevalence
      in men (not women) was also lower (26% vs. 41%) and together these inequalities
      are likely to have contributed to the higher CVD mortality in middle-income
      countries. Declines in CVD mortality have seen cancer becoming a more common
      cause of death in a number of high-income member countries, but in middle-income
      countries declines in CVD mortality have been less consistent where CVD remains
      the leading cause of death. Inequalities in CVD mortality are emphasized by the
      smaller contribution they make to potential years of life lost in high-income
      countries compared with middle-income countries both for women (13% vs. 23%) and
      men (20% vs. 27%). The downward mortality trends for CVD may, however, be
      threatened by the emerging obesity epidemic that is seeing rates of diabetes
      increasing across all the ESC member countries. Survey data from the National
      Cardiac Societies showed that rates of cardiac catheterization and coronary
      artery bypass surgery, as well as the number of specialist centres required to
      deliver them, were greatest in the high-income member countries of the ESC. The
      Atlas confirmed that these ESC member countries, where the facilities for the
      contemporary treatment of coronary disease were best developed, were often those
      in which declines in coronary mortality have been most pronounced. Economic
      resources were not the only driver for delivery of equitable cardiovascular
      health care, as some middle-income ESC member countries reported rates for
      interventional procedures and device implantations that matched or exceeded the
      rates in wealthier member countries. Conclusion: In documenting national CVD
      statistics, the Atlas provides valuable insights into the inequalities in risk
      factors, health care delivery, and outcomes of CVD across the ESC member
      countries. The availability of these data will underpin the ESC's ambitious
      mission 'to reduce the burden of cardiovascular disease' not only in its member
      countries but also in nation states around the world.

PMID- 29190380
TI  - Relationship-centered health care as a Lean intervention.
AB  - Continuous improvement efforts, recognized in much literature as Lean management
      techniques have been used in efforts to improve efficiency in democratic health
      care contexts for some time to varying degrees of success. The complexity of the
      health care system is magnified by the sheer number of processes and sub
      processes required to deliver value within a bureaucratic environment, while
      maintaining some level of compassionate and personalized care. There is inherent
      tension between what is required to be efficient and what is required to be
      caring and this conflict presses against Lean practice at the level of
      delivery.Administration and care intersect at the point of the patient's
      experience. In order to achieve the dual goals of improved value and lower costs,
      the application of Lean thinking for meaningful health care reform must
      acknowledge the fundamental dichotomy between the impersonal tasks required to
      provide health services, and human interactions. Meaningful health care reform
      requires an acknowledgement of this distinction, currently not recognized in
      literature. While administrative process improvements are necessary, they are
      insufficient to achieve a sustainable and caring health care system. Lean
      thinking must be applied differently for administrative processes and patient
      care encounters, because these are fundamentally different processes. In this
      way, Lean principles will effectively contribute to sustainable health system
      improvements.

PMID- 29190382
TI  - The epigenetic clock and telomere length are independently associated with
      chronological age and mortality.

PMID- 29190381
TI  - Expression of MdCCD7 in the scion determines the extent of sylleptic branching
      and the primary shoot growth rate of apple trees.
AB  - Branching has a major influence on the overall shape and productivity of a plant.
      Strigolactones (SLs) have been identified as plant hormones that have a key role
      in suppressing the outgrowth of axillary meristems. CAROTENOID CLEAVAGE
      DIOXYGENASE (CCD) genes are integral to the biosynthesis of SLs and are well
      characterized in annual plants, but their role in woody perennials is relatively
      unknown. We identified CCD7 and CCD8 orthologues from apple and demonstrated that
      MdCCD7 and MdCCD8 are able to complement the Arabidopsis branching mutants max3
      and max4 respectively, indicating conserved function. RNAi lines of MdCCD7 show
      reduced gene expression and increased branching in apple. We performed reciprocal
      grafting experiments with combinations of MdCCD7 RNAi and wild-type 'Royal Gala'
      as rootstocks and scion. Unexpectedly, wild-type roots were unable to suppress
      branching in MdCCD7 RNAi scions. Another key finding was that MdCCD7 RNAi scions
      initiated phytomers at an increased rate relative to the wild type, resulting in
      a greater node number and primary shoot length. We suggest that localized SL
      biosynthesis in the shoot, rather than roots, controls axillary bud outgrowth and
      shoot growth rate in apple.

PMID- 29190383
TI  - Bionic Vision, Social Work, and Community Development: A Research Participant's
      Reflections.
AB  - This article discusses bionic vision through the author's experiences as
      Australia's first research participant in an early prototype bionic eye trial.
      During her two-year participation, she drew on various theoretical perspectives,
      including critical and community development approaches that not only influence
      her professional social work perspective, but extend to her personal worldview.
      In a rapidly emerging biotechnological age, this article contributes a holistic
      perspective, bringing into focus theory and practice; issues of human experience,
      human rights, and oppressive relationships; tensions between agency and structure
      (particularly relating to disability from a social model of disability and the
      medical model); and practical applications of artificial vision. Beyond its
      practical applications, illuminated is the relevance of community development
      values and principles such as a sense of connectedness, participation, and
      empowerment, which are understood in terms of an antioppressive perspective. The
      article concludes by recognizing the potential benefit of bionic vision for
      vision-impaired and blind people in their everyday lives.

PMID- 29190384
TI  - General practitioner and nurse prescriber experiences of prescribing antibiotics
      for respiratory tract infections in UK primary care out-of-hours services (the
      UNITE study).
AB  - Background: Interventions are needed to reduce unnecessary antibiotic prescribing
      for respiratory tract infections (RTIs). Although community antibiotic
      prescribing appears to be decreasing in the UK, figures for out-of-hours (OOH)
      prescribing have substantially increased. Understanding the factors influencing
      prescribing in OOH and any perceived differences between general practitioner
      (GP) and nurse prescriber (NP) prescribing habits may enable the development of
      tailored interventions promoting optimal prescribing in this setting. Objectives:
      To explore UK GP and NP views on and experiences of prescribing antibiotics for
      RTIs in primary care OOH services. Methods: Thirty semi-structured interviews
      were conducted with GPs and NPs working in primary care OOH services. Inductive
      thematic analysis was used to analyse data. Results: The research shows that
      factors particular to OOH influence antibiotic prescribing, including a lack of
      patient follow-up, access to patient GP records, consultation time, working
      contracts and implementation of feedback, audit and supervision. NPs reported
      perceptions of greater accountability for their prescribing compared with GPs and
      reported they had longer consultations during which they were able to discuss
      decisions with patients. Participants agreed that more complex cases should be
      seen by GPs and highlighted the importance of consistency of decision making,
      illness explanations to patients as well as a perception that differences in
      clinical training influence communication with patients and antibiotic
      prescribing decisions. Conclusions: Environmental and social factors in OOH
      services and a mixed healthcare workforce provide unique influences on antibiotic
      prescribing for RTIs, which would need to be considered in tailoring
      interventions that promote prudent antibiotic prescribing in OOH services.

PMID- 29190385
TI  - E-motif formed by extrahelical cytosine bases in DNA homoduplexes of
      trinucleotide and hexanucleotide repeats.
AB  - Atypical DNA secondary structures play an important role in expandable
      trinucleotide repeat (TR) and hexanucleotide repeat (HR) diseases. The cytosine
      mismatches in C-rich homoduplexes and hairpin stems are weakly bonded;
      experiments show that for certain sequences these may flip out of the helix core,
      forming an unusual structure termed an 'e-motif'. We have performed molecular
      dynamics simulations of C-rich TR and HR DNA homoduplexes in order to
      characterize the conformations, stability and dynamics of formation of the e
      motif, where the mismatched cytosines symmetrically flip out in the minor groove,
      pointing their base moieties towards the 5'-direction in each strand. TRs have
      two non-equivalent reading frames, (GCC)n and (CCG)n; while HRs have three:
      (CCCGGC)n, (CGGCCC)n, (CCCCGG)n. We define three types of pseudo basepair steps
      related to the mismatches and show that the e-motif is only stable in (GCC)n and
      (CCCGGC)n homoduplexes due to the favorable stacking of pseudo GpC steps (whose
      nature depends on whether TRs or HRs are involved) and the formation of hydrogen
      bonds between the mismatched cytosine at position i and the cytosine (TRs) or
      guanine (HRs) at position i - 2 along the same strand. We also characterize the
      extended e-motif, where all mismatched cytosines are extruded, their extra
      helical stacking additionally stabilizing the homoduplexes.

PMID- 29190386
TI  - Conditioning of Leaf Detritus Modulates Density-Dependent Growth of Aedes
      triseriatus Larvae (Diptera: Culicidae).
AB  - Ration of food per capita of larval population is widely thought to limit
      mosquito production from container habitats, directly reflecting resource
      limitation. In this study, the importance of density-dependent resource
      limitation on larval Aedes triseriatus (Say) (Diptera: Culicidae) depended on the
      degree of microbial conditioning of senescent leaf detritus in surrogate tree
      holes. Density and ration strongly affected emergence, total female mass, and
      mean female mass of populations grown on leaves that had conditioned for 3 d, but
      had less impact when larval populations were grown on leaves that had conditioned
      for 1 mo. Ration per capita was a stronger predictor (50-94% of the variance) of
      all growth parameters measured for populations grown on leaves conditioned for 3
      d compared with 1 mo (2-66% of variance), with the exception of development time.
      Larvae grew faster and to a larger body size on leaves conditioned for 3 d at low
      densities of larvae and a higher ration per capita. However, populations grown on
      leaves conditioned for 1 mo produced equal or more total mass and individuals of
      higher average mass than when grown on leaves conditioned for 3 d in treatments
      with low ration per capita. Well-conditioned detritus, representing the degree of
      microbial colonization of the organic material, must reflect the typical
      condition in tree holes with unconditioned leaves atypical. Therefore, results of
      this study suggest that experiments using well-conditioned leaves better estimate
      growth responses, including moderated density dependence and less importance of
      ration per capita, than experiments using unconditioned detritus.

PMID- 29190387
TI  - Chronic hyperandrogenemia in the presence and absence of a western-style diet
      impairs ovarian and uterine structure/function in young adult rhesus monkeys.
AB  - STUDY QUESTION: Does chronic hyperandrogenemia beginning at menarche, in the
      absence and presence of a western-style diet (WSD), alter ovarian and uterine
      structure-function in young adult rhesus monkeys? SUMMARY ANSWER: Phenotypic
      alterations in ovarian and uterine structure/function were induced by exogenous
      testosterone (T), and compounded in the presence of a WSD (T+WSD). WHAT IS KNOWN
      ALREADY: Hyperandrogenemia is a well-established component of PCOS and is
      observed in adolescent girls, indicating a potential pubertal onset of disease
      symptoms. Obesity is often associated with hyperandrogenemia and it is
      hypothesized that metabolic dysfunction exacerbates PCOS symptoms. STUDY DESIGN,
      SIZE, DURATION: Macaque females (n = 40) near the onset of menarche (~2.5 years
      of age) were assigned to a 2 by 2 factorial cohort design. Effects on
      reproductive characteristics were evaluated after 3 years of treatment.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Rhesus macaques (Macaca mulatta) were
      fed either a normal balanced diet (n = 20) or a WSD (n = 20). Additionally,
      implants containing cholesterol (n = 20) or T (n = 20) were implanted
      subcutaneously to elevate serum T approximately 5-fold. This resulted in
      treatment groups of controls (C), T, WSD and T+WSD (n = 10/group). Vaginal
      swabbing was performed daily to detect menses. After 3 years of treatment, daily
      serum samples from one menstrual cycle were assayed for hormone levels. Ovarian
      structure was evaluated in the early follicular phase by 3D/4D ultrasound.
      Uterine endometrial size and ovarian/luteal vascular function was also evaluated
      in subgroups (n = 6/group) in the late follicular and mid-luteal phases by 3D/4D
      ultrasound and contrast-enhanced ultrasound, respectively. Expression of steroid
      hormone receptors and markers of decidualization and endometrial receptivity were
      assessed in endometrial biopsies at mid-luteal phase. MAIN RESULTS AND THE ROLE
      OF CHANCE: Approximately 90% of menstrual cycles appeared ovulatory with no
      differences in frequency or duration between groups. Serum estradiol (E2) levels
      during the early follicular phase were greatest in the T alone group, but reduced
      in T+WSD (P < 0.02). Serum LH was elevated in the T group (P < 0.04); however,
      there were no differences among groups in FSH levels (P > 0.13). Ovarian size at
      menses tended to be greater in the WSD groups (P < 0.07) and antral follicles >=1
      mm were more numerous in the T+WSD group (P < 0.05). Also, females in T and T+WSD
      groups displayed polycystic ovarian morphology (PCOM) at greater frequency than C
      or WSD groups (P < 0.01). Progesterone (P4) levels during the luteal phase were
      reduced in the T+WSD group compared to C and T groups (P < 0.05). Blood volume
      (BV) and vascular flow (VF) within the corpus luteum was reduced in all treatment
      groups compared to C (P < 0.01, P = 0.03), with the WSD alone group displaying
      the slowest BV and VF (P < 0.05). C and WSD groups displayed endometrial glands
      at mid-luteal phase with low estrogen receptor 1 (ESR1) and progesterone receptor
      (PGR) mRNA and immunohistochemical staining in the functionalis zone, but
      appreciable PGR in the stroma. In contrast, T and T+WSD treatment resulted in
      glands with less secretory morphology, high ESR1 expression in the glandular
      epithelium and low PGR in the stroma. Endometrial levels of TIMP3 and MMP26 mRNA
      and immunostaining were also decreased in the T and T+WSD groups, whereas AR
      expression was unchanged. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR
      CAUTION: Females are young adults, so effects could change as they reach prime
      reproductive age. The T level generated for hyperandrogenemia may be somewhat
      greater than the 3-4-fold increase observed in adolescent girls, but markedly
      less than those observed in male monkeys or adolescent boys. WIDER IMPLICATIONS
      OF THE FINDINGS: Alterations to ovarian and uterine structure-function observed
      in T and, in particular, T+WSD-treated female macaques are consistent with some
      of the features observed in women diagnosed with polycystic ovary syndrome
      (PCOS), and suggest impaired fertility. STUDY FUNDING/COMPETING INTEREST(S):
      Research reported in this publication was supported by the Eunice Kennedy Shriver
      National Institute of Child Health & Human Development (NICHD) of the National
      Institutes of Health (NIH) under Award Number P50HD071836 (to RLS). The content
      is solely the responsibility of the authors and does not necessarily represent
      the official views of the NIH. Additional funding was provided by Office of the
      Director, NIH under Award Number P51OD011092 (Support for National Primate
      Research Center). Authors declare no competing interests.

PMID- 29190388
TI  - INP1 involvement in pollen aperture formation is evolutionarily conserved and may
      require species-specific partners.
AB  - Pollen wall exine is usually deposited non-uniformly on the pollen surface, with
      areas of low exine deposition corresponding to pollen apertures. Little is known
      about how apertures form, with the novel Arabidopsis INP1 (INAPERTURATE POLLEN1)
      protein currently being the only identified aperture factor. In developing
      pollen, INP1 localizes to three plasma membrane domains and underlies formation
      of three apertures. Although INP1 homologs are found across angiosperms, they
      lack strong sequence conservation. Thus, it has been unclear whether they also
      act as aperture factors and whether their sequence divergence contributes to
      interspecies differences in aperture patterns. To explore the functional
      conservation of INP1 homologs, we used mutant analysis in maize and tested
      whether homologs from several other species could function in Arabidopsis. Our
      data suggest that the INP1 involvement in aperture formation is evolutionarily
      conserved, despite the significant divergence of INP1 sequences and aperture
      patterns, but that additional species-specific factors are likely to be required
      to guide INP1 and to provide information for aperture patterning. To determine
      the regions in INP1 necessary for its localization and function, we used fragment
      fusions, domain swaps, and interspecific protein chimeras. We demonstrate that
      the central portion of the protein is particularly important for mediating the
      species-specific functionality.

PMID- 29190389
TI  - A Bayesian Approach for Measurements of Stray Neutrons at Proton Therapy
      Facilities: Quantifying Neutron Dose Uncertainty.
AB  - Bonner sphere measurements are typically analyzed using unfolding codes. It is
      well known that it is difficult to get reliable estimates of uncertainties for
      standard unfolding procedures. An alternative approach is to analyze the data
      using Bayesian parameter estimation. This method provides reliable estimates of
      the uncertainties of neutron spectra leading to rigorous estimates of
      uncertainties of the dose. We extend previous Bayesian approaches and apply the
      method to stray neutrons in proton therapy environments by introducing a new
      parameterized model which describes the main features of the expected neutron
      spectra. The parameterization is based on information that is available from
      measurements and detailed Monte Carlo simulations. The validity of this approach
      has been validated with results of an experiment using Bonner spheres carried out
      at the experimental hall of the OncoRay proton therapy facility in Dresden.

PMID- 29190390
TI  - Mistletoe-induced growth reductions at the forest stand scale.
AB  - The hemiparasite European mistletoe (Viscum album L.) adversely affects growth
      and reproduction of the host Scots pine (Pinus sylvestris L.) and in consequence
      may lead to tree death. Here, we aimed to estimate mistletoe-induced losses in
      timber yield applying the process-based forest growth model 4C. The parasite was
      implemented into the eco-physiological forest growth model 4C using (literature
      derived) established impacts of the parasite on the tree's water and carbon
      cycle. The amended model was validated simulating a sample forest stand in the
      Berlin area (Germany) comprising trees with and without mistletoe infection. At
      the same forest stand, tree core measurements were taken to evaluate simulated
      and observed growth. A subsample of trees were harvested to quantify biomass
      compartments of the tree canopy and to derive a growth function of the mistletoe
      population. The process-based simulations of the forest stand revealed 27%
      reduction in basal area increment (BAI) during the last 9 years of heavy
      infection, which was confirmed by the measurements (29% mean growth reduction).
      The long-term simulations of the forest stand before and during the parasite
      infection showed that the amended forest growth model 4C depicts well the BAI
      growth pattern during >100 years and also quantifies well the mistletoe-induced
      growth reductions in Scots pine stands.

PMID- 29190392
TI  - Reminiscence in Everyday Conversations: A Naturalistic Observation Study of Older
      Adults.
AB  - Objectives: We examined older adults' social reminiscence behavior in everyday
      life, and the relation between reminiscence functions and well-being. Method: The
      sample included 2,164 sound snippets that included speech from 45 healthy older
      adults. We examined reminiscence in daily conversations using the Electronically
      Activated Recorder. Across four days, we collected a random sample of about 280
      sound files (30 seconds long) per participant. Participants' utterances were
      coded for whether they included reminiscence, for their functions and
      conversation partners. Participants completed mood and life satisfaction
      measures. Results: Participants reminisced in 5% of their utterances (range: 0%
      29%). They reminisced in 40% of cases with friends, 32.8% with their partner and
      8% with their children/relatives. Three reminiscence functions were observed:
      identity, teaching/informing, and conversation. Participants' reminiscence served
      the identity function while they were reminiscing with their partner and
      children. Participants reminisced to teach/inform while reminiscing with their
      children and strangers. Reminiscing for conversation occurred mainly with partner
      and friends. We found positive relations between life satisfaction and identity,
      teach/inform, and conversation functions. Mood had a negative relation with
      identity and teach/inform functions. Discussion: This is the first study to take
      a naturalistic observation approach to reminiscence and to build on self-report
      data.

PMID- 29190391
TI  - Radiotherapy for locally advanced resectable T3-T4 laryngeal cancer-does
      laryngeal preservation strategy compromise survival?
AB  - With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was
      explored with the aim of improving maintenance of quality of life. Induction
      chemotherapy (ICT) following radiotherapy (RT) was considered a viable option
      because of its high initial response rate without hampering of overall survival
      (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the
      standard of care for LP, showing the best LP ratio. For enhancing treatment
      intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed
      superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost
      all randomized controlled trials investigating ICT include not only operable
      (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced
      with a dilemma regarding application in daily practice. In addition, increased
      treatment intensity causes augmentation of adverse events, which might reduce
      compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects
      [bioradiotherapy (BRT)], emerged as another option. However, little evidence has
      confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations.
      In spite of these developments, the OS of patients with laryngeal cancer has not
      improved for several decades. In fact, several studies indicated a decrease in OS
      during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was
      not the case in most institutions. Currently, no other treatment has better OS
      than surgery. The eligibility criteria for LP and/or surgery largely depend upon
      the available expertise and experience, which differ from one institution to
      another. Therefore, a multidisciplinary team is required for the treatment of LP.

PMID- 29190393
TI  - Exchanging missives and missiles: the roles of extracellular vesicles in plant
      pathogen interactions.

PMID- 29190394
TI  - Acetylation of 53BP1 dictates the DNA double strand break repair pathway.
AB  - P53-binding protein 1 (53BP1) plays critical roles in DNA double strand break
      (DSB) repair by promoting non-homologous end joining (NHEJ), and loss of 53BP1
      abolishes PARPi sensitivity in BRCA1-deficient cells by restoring homologous
      recombination (HR). 53BP1 is one of the proteins initially recruited to sites of
      DSBs via recognition of H4K20me2 through the Tudor-UDR domain and H2AK15ub
      through the UDR motif. Although extensive studies have been conducted, it remains
      unclear how the post-translational modification of 53BP1 affects DSB repair
      pathway choice. Here, we identified 53BP1 as an acetylated protein and determined
      that acetylation of 53BP1 inhibit NHEJ and promote HR by negatively regulating
      53BP1 recruitment to DSBs. Mechanistically, CBP-mediated acetylation of
      K1626/1628 in the UDR motif disrupted the interaction between 53BP1 and
      nucleosomes, subsequently blocking the recruitment of 53BP1 and its downstream
      factors PTIP and RIF1 to DSBs. Hyperacetylation of 53BP1, similar to depletion of
      53BP1, restored PARPi resistance in BRCA1-deficient cells. Interestingly, 53BP1
      acetylation was tightly regulated by HDAC2 to maintain balance between the HR and
      NHEJ pathways. Together, our results demonstrate that the acetylation status of
      53BP1 plays a key role in its recruitment to DSBs and reveal how specific 53BP1
      modification modulates the choice of DNA repair pathway.

PMID- 29190395
TI  - Subjective social status and trajectories of self-rated health status: a
      comparative analysis of Japan and the United States.
AB  - Background: Japanese society is more egalitarian than the United States as is
      reflected by the lower degree of prevalence of social inequalities in health. We
      examined whether subjective socioeconomic status is associated with different
      trajectories of self-rated health (SRH), and whether this relationship differs
      between the United States and Japan. Methods: We analyzed the responses of 3968
      Americans from the survey Midlife in the United States, 2004-06, and the
      responses of 989 Japanese from the survey Midlife in Japan, 2008. We conducted a
      multilevel analysis with three self-ratings of health (10 years ago, current and
      10 years in the future) nested within individuals and nested within 10 levels of
      subjective social status. Age, sex, educational level and subjective financial
      situation were adjusted. Results: After making statistical adjustments for
      confounding variables, respondents in Japan continued to report lower average
      levels of health. However, the rate of expected decline in SRH over the next
      decade was strongly socially patterned in the United States, whereas it was not
      in Japan. Conclusion: The Japanese showed no disparity in the anticipated
      trajectory of SRH over time, whereas the Americans showed a strong social class
      gradient in future trajectories of SRH.

PMID- 29190397
TI  - The international nucleotide sequence database collaboration.
AB  - For more than 30 years, the International Nucleotide Sequence Database
      Collaboration (INSDC; http://www.insdc.org/) has been committed to capturing,
      preserving and providing access to comprehensive public domain nucleotide
      sequence and associated metadata which enables discovery in biomedicine,
      biodiversity and biological sciences. Since 1987, the DNA Data Bank of Japan
      (DDBJ) at the National Institute for Genetics in Mishima, Japan; the European
      Nucleotide Archive (ENA) at the European Molecular Biology Laboratory's European
      Bioinformatics Institute (EMBL-EBI) in Hinxton, UK; and GenBank at National
      Center for Biotechnology Information (NCBI), National Library of Medicine,
      National Institutes of Health in Bethesda, Maryland, USA have worked
      collaboratively to enable access to nucleotide sequence data in standardized
      formats for the worldwide scientific community. In this article, we reiterate the
      principles of the INSDC collaboration and briefly summarize the trends of the
      archival content.

PMID- 29190396
TI  - Distinct reaction mechanisms for hyaluronan biosynthesis in different kingdoms of
      life.
AB  - Hyaluronan (HA) is an acidic high molecular weight cell surface polysaccharide
      ubiquitously expressed by vertebrates, some pathogenic bacteria and even viruses.
      HA modulates many essential physiological processes and is implicated in numerous
      pathological conditions ranging from autoimmune diseases to cancer. In various
      pathogens, HA functions as a non-immunogenic surface polymer that reduces host
      immune responses. It is a linear polymer of strictly alternating glucuronic acid
      and N-acetylglucosamine units synthesized by HA synthase (HAS), a membrane
      embedded family-2 glycosyltransferase. The enzyme synthesizes HA and secretes the
      polymer through a channel formed by its own membrane-integrated domain. To reveal
      how HAS achieves these tasks, we determined the biologically functional units of
      bacterial and viral HAS in a lipid bilayer environment by co-immunoprecipitation,
      single molecule fluorescence photobleaching, and site-specific cross-linking
      analyses. Our results demonstrate that bacterial HAS functions as an obligate
      homo-dimer with two functional HAS copies required for catalytic activity. In
      contrast, the viral enzyme, closely related to vertebrate HAS, functions as a
      monomer. Using site-specific cross-linking, we identify the dimer interface of
      bacterial HAS and show that the enzyme uses a reaction mechanism distinct from
      viral HAS that necessitates a dimeric assembly.

PMID- 29190398
TI  - The response of young adult smokers and non-smokers in the United Kingdom to
      dissuasive cigarettes: An online survey.
AB  - Introduction: The cigarette stick is an important communications tool as well as
      the object of consumption. We explored young adults' responses to cigarettes
      designed to be dissuasive. Methods: Data come from a cross-sectional online
      survey, conducted in September 2015, with 16-24 year old smokers and non-smokers
      (N=997) in the United Kingdom. Participants were shown images of a standard
      cigarette (white cigarette paper with imitation cork filter), a standard
      cigarette displaying the warning 'Smoking kills' on the cigarette paper, and an
      unattractively coloured cigarette (green cigarette paper and filter). They were
      asked to rate each of the three cigarettes, shown individually, on eight
      perception items, and to rate the three cigarettes, shown together, on how likely
      they would be to try them. Ordering of the cigarettes and questions, with the
      exception of the question on trial, was randomised. Results: The eight
      perceptions items were combined to form a composite measure of cigarette
      perceptions. For smokers and non-smokers, the two dissuasive cigarettes
      (cigarette with warning, green cigarette) were rated significantly less
      favourably than the standard cigarette, and less likely to encourage trial. For
      cigarette perceptions no significant interaction was detected between cigarette
      style and smoking status or susceptibility to smoke among never smokers. A
      significant interaction was found for likelihood of trying the cigarettes, with
      dissuasive cigarettes having a greater impact with smokers than non-smokers.
      Conclusions: This study suggests that dissuasive cigarettes may help to reduce
      the desirability of cigarettes. Implications: The cigarette stick is the object
      of tobacco consumption, which is seen every time a cigarette is smoked. It is
      also an increasingly important promotional tool for tobacco companies. In this
      study, young adults rated two dissuasive cigarettes (a green coloured cigarette
      and a cigarette displaying a health warning) more negatively than a standard
      cigarette, and considered them less likely to encourage product trial. Our
      findings suggest that it may be possible to reduce the desirability of cigarette
      sticks by altering their design, e.g., with the addition of a warning or use of
      an unattractive colour.

PMID- 29190399
TI  - Creating a Medical Workforce That Looks Like America: Community Colleges Have a
      Major Role.

PMID- 29190400
TI  - Interest in Family Medicine Among US Medical Students and Its Association With a
      Community College Academic Pathway.
AB  - BACKGROUND AND OBJECTIVES: One-third of all medical students attend a community
      college (CC) on their path to medical school. The objective of this study was to
      examine the association between CC participation and initial specialty of
      interest among US allopathic medical students. METHODS: We performed a national
      cross-sectional study of allopathic medical students who completed the 2012
      Association of American Medical Colleges' Matriculating Student Questionnaire.
      Bivariate and logistic regression analyses were conducted. RESULTS: A total of
      9,885 medical student respondents were included in the study sample, consisting
      of 7,035 (71%) non-CC pathway, and 2,850 (29%) CC pathway participants. CC
      pathway participants were more likely to express intent to specialize in family
      medicine (272/2,850 [10%] vs 463/7,035 [7%], P<.001), compared to those on the
      non-CC path. CC pathway participants had higher odds of intent to specialize in
      family medicine (adjusted odds ratio [AOR]=1.32; 95% CI 1.13-1.56, P<0.001),
      compared to those on the non-CC path. Women, independent of college pathway, were
      nearly two times more likely to express an intention to specialize in family
      medicine, and three times more likely to express an intention to specialize in
      pediatrics than men. CONCLUSIONS: Medical students who used a CC pathway are more
      likely to have intentions to specialize in family medicine, compared to those on
      the non-CC path.

PMID- 29190401
TI  - Addressing Food Insecurity in Family Medicine and Medical Education.
AB  - BACKGROUND AND OBJECTIVES: Food insecurity is associated with poor health
      outcomes, yet is not routinely addressed in health care. This study was conducted
      to determine if education regarding food insecurity as a health issue could
      modify knowledge, attitudes, and clinical behavior. METHODS: Educational sessions
      on food insecurity and its impact on health were conducted in 2015 at three
      different family medicine residency programs and one medical school. A pre/post
      survey was given immediately before and after this session. Attendees were
      encouraged to identify and implement individual and system-based changes to
      integrate food insecurity screening and referrals into their clinical practices.
      Participants completed follow-up surveys approximately 1 year later, and the
      authors obtained systems-level data from electronic health records and databases.
      Pre/post means (SD) were compared using t-tests. The numbers of patients screened
      and referred were calculated. RESULTS: Eighty-five participants completed the
      pre/post survey during the educational sessions (51 medical students, 29
      residents, 5 faculty). Self-reported knowledge of food insecurity, resources, and
      willingness to discuss with patients increased (P<0.0001 for all). Each program
      identified a feasible systems-based change. Follow-up surveys demonstrated
      increased discussion of food insecurity during clinical visits and referrals to
      food resources. Over 1,600 patients were screened for food insecurity as a result
      of systems-based changes. CONCLUSIONS: Educational interventions focused on the
      role of food insecurity in health can produce improvements in knowledge and
      attitudes toward addressing food insecurity, increase discussions with patients
      about food insecurity, and result in measurable patient and systems-level
      changes.

PMID- 29190402
TI  - Resident and Residency Characteristics Associated With Self-reported Preparedness
      for Population Health Management.
AB  - BACKGROUND AND OBJECTIVES: Population health management (PHM) is an important
      function of primary care with potential to improve outcomes and decrease costs,
      but is also among the most difficult strategies to implement in both practices
      and residency training. Our objective was to determine resident and residency
      program characteristics associated with graduates' reported preparation to
      perform PHM. METHODS: We used data from the American Board of Family Medicine
      (ABFM) Certification Examination registration questionnaire in 2014 and 2015 and
      ABFM administrative data. Resident PHM preparedness was assessed via a single,
      self-reported question. Bivariate analysis and logistic multilevel regression
      were performed to determine independent associations between characteristics and
      reported PHM preparedness. Odds ratios were converted to risk ratios given the
      high prevalence of the outcome. RESULTS: Our sample included 6,135 residents from
      442 family medicine residencies. Sixty-nine percent (n=4,240) reported being
      extremely or moderately prepared to perform PHM. No residency program
      characteristics showed an association with reported PHM preparedness. Resident
      characteristics independently associated with reported preparedness included
      being an international medical graduate (IMG) (RR=1.21 [1.07-1.35]) and of
      Hispanic ethnicity. Reporting greater preparedness to use health information
      tools, to lead quality improvement projects, and to provide care in different
      settings were also associated with reported PHM preparedness. CONCLUSIONS:
      Similar to a study of practicing physicians, we found that IMGs are more likely
      to report preparedness to perform PHM. This suggests that elements of
      international medical education may better inculcate PHM principles, and that
      these elements could be used to produce physicians better prepared to manage
      population health.

PMID- 29190403
TI  - Family Medicine Didactics Revisited.
AB  - BACKGROUND AND OBJECTIVES: All family medicine programs are required to provide
      specialty-specific didactic conferences for residents. Since a baseline study of
      family medicine didactic formats was published in 2000, training requirements
      have changed, core content has evolved, and new teaching strategies have been
      recommended. The present study examines the characteristics of current family
      medicine didactics, compares current and past conference format data, and
      identifies factors affecting content selection. METHODS: The survey used in the
      prior conference formats study was distributed to all US family medicine
      programs. All questions from the original survey were repeated, and items
      regarding factors affecting conference content and threats to conferences were
      added. RESULTS: The survey response rate was 66%. The majority of family medicine
      programs endorse block formats for structuring conferences. Compared to the
      original study, programs are devoting significantly more hours to didactics on
      fewer days. Family medicine faculty and residents are responsible for 70% of
      didactic offerings (also a significant shift), and 87% of programs use a core
      curriculum. In over 70% of programs, some residents are unavailable for
      conferences due to work restrictions or service demands. The Accreditation
      Council for Graduate Medical Education subcompetencies and Milestones have only a
      moderate impact on topic selection. CONCLUSIONS: Family medicine didactics have
      evolved in the past 15 years with a notable increase in reliance upon core
      faculty and residents to lead conferences. Reduced availability of residents
      prevents all residents from having full exposure to the didactic curriculum.
      Family medicine faculty who are taking greater responsibility for didactics are
      also faced with increased clinical and administrative duties.

PMID- 29190404
TI  - Sex Ed by Brown Med: A Student-Run Curriculum and Its Impact on Sexual Health
      Knowledge.
AB  - BACKGROUND AND OBJECTIVES: Risky sexual behavior among adolescents is a public
      health crisis. We describe a novel approach to sexual health education where
      medical students manage a curriculum for an entire seventh grade in one Rhode
      Island city to better equip students with comprehensive knowledge about sexual
      health. METHODS: Medical students were trained to teach 12 sessions to seventh
      grade students under the supervision of the classroom teacher using a curriculum
      designed by medical students and faculty (modeled on the Family Life and Sexual
      Health [FLASH] curriculum but tailored to meet the community's needs). Pre- and
      postassessment surveys were conducted during the 2015-2016 academic year. We
      analyzed survey data collected pre- and postprogram using IBM SPSS Statistics.
      RESULTS: Pre and postassessments were completed by 62% of students (74/120).
      Students completing the curriculum scored 8% higher on the postassessment vs the
      preassessment, (70.4% vs 62.32%, absolute difference=8.11%, P<0.001). Student
      knowledge improved in domains of pregnancy prevention, reproductive
      system/anatomy, general knowledge and prevention of sexually transmitted
      infections (STIs), safe sex practices, sexual assault, and sexual decision
      making. Respondents' perception of the importance of school-based sexual health
      lessons as well as their willingness to discuss sexual issues with an adult
      increased after completing the program. CONCLUSIONS: A year-long, middle school
      based sexual health program taught by medical students showed significant
      improvements in sexual health knowledge and increased willingness to engage in
      dialogue about sex with trusted adults. Adolescents may benefit from long-term
      interaction and instruction about sexual education from medical students.

PMID- 29190405
TI  - Are Self-study Procedural Teaching Methods Effective? A Pilot Study of a Family
      Medicine Residency Program.
AB  - BACKGROUND AND OBJECTIVES: A family medicine residency is a unique training
      environment where residents are exposed to care in multiple settings, across all
      ages. Procedures are an integral part of family medicine practice. Family
      medicine residency (FMR) programs are tasked with the job of teaching these
      skills at a level of intensity and frequency that allows a resident to achieve
      competency of such skills. In an environment that is limited by work hour
      restrictions, self-study teaching methods are one way to ensure all residents
      receive the fundamental knowledge of how to perform procedures. We developed and
      evaluated the efficacy of a self-study procedure teaching method and procedure
      evaluation checklist. METHODS: A self-study procedure teaching intervention was
      created, consisting of instructional articles and videos on three procedures. To
      assess the efficacy of the intervention, and the competency of the residents, pre
      and postintervention procedure performance sessions were completed. These
      sessions were reviewed and scored using a standardized procedure performance
      checklist. RESULTS: All 24 residents participated in the study. Overall, the
      resident procedure knowledge increased on two of the three procedures studied,
      and ability to perform procedure according to expert-validated checklist improved
      significantly on all procedures. CONCLUSIONS: A self-study intervention is a
      simple but effective way to increase and improve procedure training in a way that
      fits the complex scheduling needs of a residency training program. In addition,
      this study demonstrates that the procedure performance checklists are a simple
      and reliable way to increase assessment of resident procedure performance skills
      in a residency setting.

PMID- 29190406
TI  - Development of a Multifaceted Health Disparities Curriculum for Medical
      Residents.
AB  - BACKGROUND AND OBJECTIVES: Health disparities education is required during
      residency training. However, residency program directors cite numerous barriers
      to implementing disparities curricula, and few publications describing successful
      disparities curricula exist in the literature. In this report, we describe the
      development, implementation, and early evaluation of a longitudinal health
      disparities curriculum for resident physicians. We provide resource references,
      process, and didactic toolkits to facilitate use by other residency programs.
      METHODS: We used a standard, six-step model for curricular design,
      implementation, and evaluation. We assessed feasibility of curricular development
      including practicality (program cost and time requirements) and demand (resident
      engagement). We also assessed program and learner outcomes, including number of
      didactic and clinic sessions delivered and resident preparedness, attitudes, and
      skill in caring for vulnerable patients. RESULTS: We designed, implemented, and
      evaluated our curriculum in less than 1 year, with no external funding. Time
      costs included 100 chief resident and 20 faculty hours for curricular
      development, followed by 20 chief resident and 16 faculty hours for
      implementation. In the first year of our curriculum, 21% of residents (16 of 75)
      participated. We created eight didactic sessions and delivered four as intended.
      Residents provided 84 free clinic sessions for uninsured patients and reported
      increased preparedness and skill caring for vulnerable patients in 15 of 20
      measured domains. Residents also reported 20 commitments to change on themes that
      comprehensively reflected the content of our first curricular year. CONCLUSIONS:
      It is possible to design a disparities curriculum, overcome cited barriers, and
      improve educational outcomes related to the care of vulnerable patients.

PMID- 29190407
TI  - Perceptions of Nutrition Education in the Current Medical School Curriculum.
AB  - BACKGROUND AND OBJECTIVES: Although the National Academy of Sciences has
      recommended a minimum of 25 hours of nutrition education, the majority of medical
      schools offer very little to no training or education in nutrition to medical
      students during their tenure in medical school. In order to assess the relevance
      and efficacy of current levels of nutrition training as viewed by students,
      residents, and physicians, as well as possible areas for further improvement, the
      authors conducted a qualitative study exploring students' experiences. METHODS:
      Medical students, residents, and physicians at a Midwestern medical school were
      interviewed during a series of eight focus groups and one-on-one interviews.
      Results were coded and analyzed using NVivo qualitative software for emerging
      themes. RESULTS: Medical students felt nutrition was poorly integrated into the
      curriculum. They witnessed little nutrition counseling during shadowing
      experiences, and the nutrition information that was imparted was often outdated
      or incorrect. Residents stated they felt ill-prepared to offer nutrition
      counseling and desired further education in this area. CONCLUSIONS: Overall,
      medical students and physicians agreed that the nutrition education currently
      provided in medical school is inadequate. Residents stated they would benefit
      from further training in behavioral counseling in order to increase their
      confidence in educating patients about nutrition. Increasing training in these
      areas could translate into improved health outcomes.

PMID- 29190408
TI  - Transformations.

PMID- 29190409
TI  - Bambi Keith.

PMID- 29190410
TI  - Finding Professional Satisfaction in Retirement.

PMID- 29190417
TI  - Diverse Diversity.

PMID- 29190418
TI  - Interventions to change the behaviour of health professionals and the
      organisation of care to promote weight reduction in children and adults with
      overweight or obesity.
AB  - BACKGROUND: The prevalence of overweight and obesity is increasing globally, an
      increase which has major implications for both population health and costs to
      health services. This is an update of a Cochrane Review. OBJECTIVES: To assess
      the effects of strategies to change the behaviour of health professionals or the
      organisation of care compared to standard care, to promote weight reduction in
      children and adults with overweight or obesity. SEARCH METHODS: We searched the
      following databases for primary studies up to September 2016: CENTRAL, MEDLINE,
      Embase, CINAHL, DARE and PsycINFO. We searched the reference lists of included
      studies and two trial registries. SELECTION CRITERIA: We considered randomised
      trials that compared routine provision of care with interventions aimed either at
      changing the behaviour of healthcare professionals or the organisation of care to
      promote weight reduction in children and adults with overweight or obesity. DATA
      COLLECTION AND ANALYSIS: We used standard methodological procedures expected by
      Cochrane when conducting this review. We report the results for the professional
      interventions and the organisational interventions in seven 'Summary of findings'
      tables. MAIN RESULTS: We identified 12 studies for inclusion in this review,
      seven of which evaluated interventions targeting healthcare professional and five
      targeting the organisation of care. Eight studies recruited adults with
      overweight or obesity and four recruited children with obesity. Eight studies had
      an overall high risk of bias, and four had a low risk of bias. In total, 139
      practices provided care to 89,754 people, with a median follow-up of 12 months.
      Professional interventions Educational interventions aimed at general
      practitioners (GPs), may slightly reduce the weight of participants (mean
      difference (MD) -1.24 kg, 95% confidence interval (CI) -2.84 to 0.37; 3 studies,
      N = 1017 adults; low-certainty evidence).Tailoring interventions to improve GPs'
      compliance with obesity guidelines probably leads to little or no difference in
      weight loss (MD 0.05 (kg), 95% CI -0.32 to 0.41; 1 study, N = 49,807 adults;
      moderate-certainty evidence).It is uncertain if providing doctors with reminders
      results in a greater weight reduction than standard care (men: MD -11.20 kg, 95%
      CI -20.66 kg to -1.74 kg, and women: MD -1.30 kg, 95% CI [-7.34, 4.74] kg; 1
      study, N = 90 adults; very low-certainty evidence).Providing clinicians with a
      clinical decision support (CDS) tool to assist with obesity management at the
      point of care leads to little or no difference in the body mass index (BMI) z
      score of children (MD -0.08, 95% CI -0.15 to -0.01 in 378 children; moderate
      certainty evidence), CDS tools may lead to little or no difference in weight loss
      in adults: MD -0.095 kg (-0.21 lbs), P = 0.47; 1 study, N = 35,665; low-certainty
      evidence. Organisational interventions Adults with overweight or obesity may lose
      more weight if the care was provided by a dietitian (by -5.60 kg, 95% CI -4.83 kg
      to -6.37 kg) or by a doctor-dietitian team (by -6.70 kg, 95% CI -7.52 kg to -5.88
      kg; 1 study, N = 270 adults; low-certainty evidence). Shared care leads to little
      or no difference in the BMI z-score of children with obesity (adjusted MD -0.05,
      95% CI -0.14 to 0.03; 1 study, N = 105 children; low-certainty
      evidence).Organisational restructuring of the delivery of primary care (i.e.
      introducing the chronic care model) may result in a slightly lower increase in
      the BMI of children who received care at intervention clinics (BMI change:
      adjusted MD -0.21, 95% CI -0.50 to 0.07; 1 study, unadjusted MD -0.18, 95% CI 
      0.20 to -0.16; N=473 participants; moderate-certainty evidence).Mail and phone
      interventions probably lead to little or no difference in weight loss in adults
      (mean weight change (kg) using mail: -0.36, 95% CI -1.18 to 0.46; phone: -0.44,
      95% CI -1.26 to 0.38; 1 study, N = 1801 adults; moderate-certainty evidence).
      Care delivered by a nurse at a primary care clinic may lead to little or no
      difference in the BMI z-score in children (MD -0.02, 95% CI -0.16 to 0.12; 1
      study, N = 52 children; very low-certainty evidence).Two studies reported data on
      cost effectiveness: one study favoured mail and standard care over telephone
      consultations, and the other study achieved weight loss at a modest cost in both
      intervention groups (doctor and doctor-dietitian). One study of shared care
      reported similar adverse effects in both groups. AUTHORS' CONCLUSIONS: We found
      little convincing evidence for a clinically-important effect on participants'
      weight or BMI of any of the evaluated interventions. While pooled results from
      three studies indicate that educational interventions targeting healthcare
      professionals may lead to a slight weight reduction in adults, the certainty of
      these results is low. Two trials evaluating CDS tools (unpooled results) for
      improved weight management suggest little or no effect on weight or BMI change in
      adults or children with overweight or obesity. Evidence for all the other
      interventions evaluated came mostly from single studies. The certainty of the
      included evidence varied from moderate to very low for the main outcomes (weight
      and BMI). All of the evaluated interventions would need further investigation to
      ascertain their strengths and limitations as effective strategies to change the
      behaviour of healthcare professionals or the organisation of care. As only two
      studies reported on cost, we know little about cost effectiveness across the
      evaluated interventions.

PMID- 29190419
TI  - Probable Acquired QTc Prolongation and Subsequent Torsades de Pointes
      Attributable to Quetiapine.

PMID- 29190420
TI  - The Healthy Vet.

PMID- 29190421
TI  - Exciton-Exciton Annihilation Is Coherently Suppressed in H-Aggregates, but Not in
      J-Aggregates.
AB  - We theoretically demonstrate a strong dependence of the annihilation rate between
      (singlet) excitons on the sign of dipole-dipole couplings between molecules. For
      molecular H-aggregates, where this sign is positive, the phase relation of the
      delocalized two-exciton wave functions causes a destructive interference in the
      annihilation probability. For J-aggregates, where this sign is negative, the
      interference is constructive instead; as a result, no such coherent suppression
      of the annihilation rate occurs. As a consequence, room temperature annihilation
      rates of typical H- and J-aggregates differ by a factor of ~3, while an order of
      magnitude difference is found for low-temperature aggregates with a low degree of
      disorder. These findings, which explain experimental observations, reveal a
      fundamental principle underlying exciton-exciton annihilation, with major
      implications for technological devices and experimental studies involving high
      excitation densities.

PMID- 29190422
TI  - Structure-Specific Effects of Short-Chain Fatty Acids on Plasma Cholesterol
      Concentration in Male Syrian Hamsters.
AB  - Previous studies have shown that short-chain fatty acids (SCFAs) are capable of
      decreasing plasma cholesterol. However, the relative plasma-cholesterol-lowering
      activity of individual SCFAs and the underlying mechanisms by which SCFAs
      decrease plasma cholesterol remain largely unknown. The present study was done to
      compare the plasma-cholesterol-lowering potencies of four common SCFAs with 2-5
      carbons and to investigate their interactions with gene expressions of key
      regulatory factors involved in cholesterol metabolism. For 6 weeks, five groups
      of male Golden hamsters were fed either a control high-cholesterol diet (HCD) or
      one of the four experimental HCDs containing 0.5 mol of acetate (Ac), propionate
      (Pr), butyrate (Bu), or valerate (Va) per kilogram of the diet. The results
      showed that Ac, Pr, and Bu significantly reduced plasma total cholesterol (TC) by
      24, 18, and 17% (P < 0.05), respectively. All four SCFAs could decrease non-HDL
      cholesterol (non-HDL-C) and the non-HDL-C/HDL-C ratio. The addition of Ac, Pr, or
      Bu into the diet significantly promoted fecal excretion of bile acids by 121,
      113, or 120% (P < 0.05), respectively, and upregulated the gene expressions of
      sterol-regulatory-element-binding protein 2 (SREBP2), low-density-lipoprotein
      receptor (LDLR), and cholesterol 7alpha-hydroxylase (CYP7A1) in the liver. It was
      concluded that SCFAs with 2-4 carbons (Ac, Pr, and Bu) are more
      hypocholesterolemic than Va, which has 5 carbons, via enhancing fecal excretion
      of bile acids and promoting the hepatic uptake of cholesterol from the blood.

PMID- 29190423
TI  - Modeling the CH Stretch/Torsion/Rotation Couplings in Methyl Peroxy (CH3OO).
AB  - The manifestations of CH stretch/torsion/rotation coupling in the region of the
      CH stretch fundamentals are explored in the CH3OO radical. Following our earlier
      study of the fundamental in the totally symmetric CH stretch (the nu2
      fundamental), this work focuses on the other two CH stretch fundamentals, nu1 and
      nu9, which would be degenerate in the absence of a barrier in the potential along
      the methyl torsion coordinate. The simplest model, which assumes a decoupling of
      the CH stretch vibrations from the torsion, fails to reproduce several important
      features of the spectrum. Specifically, the absence of a strong peak around the
      origin of the nu1 fundamental and broadening of the strong peak near the origin
      in the observed spectrum of the nu9 fundamental are not captured by this model.
      The origins of these features are explored through two more sophisticated
      treatments of the torsion/CH stretch couplings. In the first, a four-dimensional
      potential based on the three CH stretches and the torsion is developed and shown
      to reproduce both of these features. On the basis of the results of these
      calculations, the calculated parameters are adjusted to simulate the recorded
      spectrum. To further explore the torsion/CH stretch couplings in CH3OO, a 9-state
      model Hamiltonian is developed and discussed. The implications of various types
      of couplings on the observed energy level patterns are also discussed.

PMID- 29190424
TI  - Understanding How Nitriles Stabilize Electrolyte/Electrode Interface at High
      Voltage.
AB  - Nitriles have received extensive attention for their unique ability in
      stabilizing electrolytes against oxidation at high voltages. It was generally
      believed that their anodic stability originates from a monolayer of chemisorbed
      nitrile molecules on transition-metal oxide surface, which physically expels
      carbonate molecules and prevents their oxidative decomposition. We overturn this
      belief based on calculation and experimental results and demonstrate that, like
      many high voltage film-forming electrolyte additives, nitriles also experience an
      oxidative decomposition at high voltages, and the high oxidation stability of
      nitrile-containing electrolytes is merely the consequence of a new interphasial
      chemistry. This important mechanistic correction would be of high significance in
      guiding the design of new electrolytes and interphases for the future battery
      chemistries.

PMID- 29190425
TI  - The Effects of Shear Force Transmission Across Vesicle Membranes.
AB  - We report a comprehensive study on mechanotransmission of shear forces across
      lipid bilayer membranes of giant unilamellar vesicles (GUVs). GUVs containing
      fluorescent tracer particles were immobilized on a microfluidic platform and
      exposed to shear flows. A method was developed for the visualization of three
      dimensional flows at high precision by defocusing microscopy. We quantify the
      symmetry of external flow around the GUV and show its effects on vortex flows and
      luminal dynamics. With increasing asymmetry, luminal vortices merged while liquid
      exchange in between them increased. The effect of membrane composition was
      studied through addition of cholesterol. Mechanotransmission efficacy, quantified
      by the ratio of luminal flow to external flow, ranged from epsilon = 0.094 (0 mol
      % cholesterol) to epsilon = 0.043 (16 mol % cholesterol). Our findings give new
      cues to the mechanisms underlying the sensing of strength and spatial
      distribution of shear forces by cells and the impact of membrane composition.

PMID- 29190426
TI  - Neuroprotective Effects of Acetylcholinesterase Inhibitory Peptides from Anchovy
      (Coilia mystus) against Glutamate-Induced Toxicity in PC12 Cells.
AB  - Ameliorations of cholinergic system dysfunction and oxidative stress in
      neurodegenerative diseases were main approaches to improve memory disorder. Our
      previous investigation showed that anchovy protein hydrolysate (APH) could
      attenuate scopolamine-induced memory deficits in mice by regulating
      acetylcholinesterase (AChE) activity. Therefore, peptides with AChE inhibitory
      activity in APH were explored and identified in this study, and their possible
      neuroprotective mechanisms on glutamate induced apoptosis in PC12 were also
      elucidated. Two peptides with strong AChE inhibitory capacity were identified as
      Pro-Ala-Tyr-Cys-Ser (PAYCS) and Cys-Val-Gly-Ser-Tyr (CVGSY) by ultraperformance
      liquid chromatography coupled with tandem mass spectrometry. The AChE inhibitory
      was 23.68 +/- 0.97% and 6.08 +/- 0.41%, respectively. Treatment with PAYCS and
      CVGSY could significantly (p < 0.05) increase cells viability, reduce lactate
      dehydrogenase release, reactive oxygen species (ROS) production, malondialdehyde
      content, and the ratio of Bax/Bcl-2 of glutamate-induced apoptosis PC12 cells
      (82.78 +/- 6.58 and 109.94 +/- 7.16% of control, respectively) as well as
      increase superoxide dismutase and GSH-px activities. In addition, both the
      peptides could inhibit Ca2+ influx but have no effects on mitochondrial membrane
      potential. Results indicated that AChE inhibitory peptides (PAYCS and CVGSY)
      possibly protected the PC12 cells against glutamate-induced apoptosis via
      inhibiting ROS production and Ca2+ influx. PAYCS and CVGSY might be considered as
      nutraceuticals for alleviating memory deficits.

PMID- 29190427
TI  - Controlling Long-Lived Triplet Generation from Intramolecular Singlet Fission in
      the Solid State.
AB  - The conjugated polymer poly(benzothiophene dioxide) (PBTDO1) has recently been
      shown to exhibit efficient intramolecular singlet fission in solution. We
      investigate the role of intermolecular interactions in triplet separation
      dynamics after singlet fission. We use transient absorption spectroscopy to
      determine the singlet fission rate and triplet yield in two polymers differing
      only by side-chain motif in both solution and the solid state. Whereas solid
      state films show singlet fission rates identical to those measured in solution,
      the average lifetime of the triplet population increases dramatically and is
      strongly dependent on side-chain identity. These results show that it may be
      necessary to carefully engineer the solid-state microstructure of these "singlet
      fission polymers" to produce the long-lived triplets needed to realize efficient
      photovoltaic devices.

PMID- 29190428
TI  - Measuring Loop Gain via Home Sleep Testing in Patients with Obstructive Sleep
      Apnea.

PMID- 29190429
TI  - Gene-edited MLE-15 Cells as a Model for the Hermansky-Pudlak Syndromes.
AB  - Defining the mechanisms of cellular pathogenesis in rare lung diseases such as
      Hermansky-Pudlak syndrome (HPS) is often complicated by loss of the
      differentiated phenotype of cultured primary alveolar type 2 (AT2) cells, as well
      as by a lack of durable cell lines that are faithful to both AT2-cell and rare
      disease phenotypes. We used CRISPR/Cas9 gene editing to generate a series of HPS
      specific mutations in the MLE-15 cell line. The resulting MLE-15/HPS cell lines
      exhibit preservation of AT2 cellular functions, including formation of lamellar
      body-like organelles, complete processing of surfactant protein B, and known
      features of HPS specific to each trafficking complex, including loss of protein
      targeting to lamellar bodies. MLE-15/HPS1 and MLE-15/HPS2 (with a mutation in
      Ap3beta1) express increased macrophage chemotactic protein-1, a well-described
      mediator of alveolitis in patients with HPS and in mouse models. We show that MLE
      15/HPS9 and pallid AT2 cells (with a mutation in Bloc1s6) also express increased
      macrophage chemotactic protein-1, suggesting that mice and humans with BLOC-1
      mutations may also be susceptible to alveolitis. In addition to providing a
      flexible platform to examine the role of HPS-specific mutations in trafficking
      AT2 cells, MLE-15/HPS cell lines provide a durable resource for high-throughput
      screening and studies of cellular pathophysiology that are likely to accelerate
      progress toward developing novel therapies for this rare lung disease.

PMID- 29190430
TI  - Evaluating UK National Guidance for Screening of Children for Tuberculosis. A
      Prospective Multicenter Study.
AB  - RATIONALE: To identify infected contacts of tuberculosis (TB) cases, the UK
      National Institute for Health and Care Excellence (NICE) recommended the addition
      of IFN-gamma release assays (IGRA) to the tuberculin skin test (TST) in its 2006
      TB guidelines. Treatment for TB infection was no longer recommended for children
      who screened TST-positive but IGRA-negative. OBJECTIVES: We performed a cohort
      study to evaluate the risk of TB disease in this group. METHODS: Children exposed
      to an infectious case of TB in their household were recruited from 11 pediatric
      TB clinics. TST and IGRA were performed at baseline, with IGRA repeated at 8
      weeks and TST repeated if initially negative. Children were treated according to
      2006 NICE guidelines and followed for 24 months. MEASUREMENTS AND MAIN RESULTS:
      Of 431 recruited children, 392 completed the study. We diagnosed 48 (12.2%) cases
      of prevalent TB disease, 105 (26.8%) with TB infection, and 239 (60.9%) without
      TB infection or disease. Eighteen children aged 2 years and above had a positive
      TST but persistently negative IGRA. None received TB infection treatment and none
      developed TB disease. Ninety (26.1%) children qualified for TB infection
      treatment according to 2006 NICE guidelines. In contrast, 147 (42.7%) children
      would have qualified under revised NICE guidance, issued in 2016. CONCLUSIONS: In
      this low-prevalence setting we saw no incident cases of TB disease in children
      who were TST-positive but IGRA-negative and did not receive treatment for TB
      infection. Following the latest NICE guidance, significantly more children will
      require medication.

PMID- 29190443
TI  - Corrigendum to: It's more than money: policy options to secure medical specialist
      workforce for regional centres.
AB  - Objectives Regional centres and their rural hinterlands support significant
      populations of non-metropolitan Australians. Despite their importance in the
      settlement hierarchy and the key medical services provided from these centres,
      little research has focused on their issues of workforce supply and long-term
      service requirements. In addition, they are a critical component of the recent
      growth of 'regional' hub-and-spoke specialist models of service delivery.Methods
      The present study interviewed 62 resident specialists in four regional centres,
      seeking to explore recruitment and retention factors important to their location
      decision making. The findings were used to develop a framework of possible
      evidence-informed policies.Results This article identifies key professional,
      social and locational factors, several of which are modifiable and amenable to
      policy redesign, including work variety, workplace culture, sense of community
      and spousal employment; these factors that can be targeted through initiatives in
      selection, training and incentives.Conclusions Commonwealth, state and local
      governments in collaboration with communities and specialist colleges can work
      synergistically, with a multiplicity of interdigitating strategies, to ensure a
      positive approach to the maintenance of a critical mass of long-term rural
      specialists.What is known about the topic? Rural origin increases likelihood of
      long-term retention to rural locations, with rural clinical school training
      associated with increased rural intent. Recruitment and retention policy has been
      directed at general practitioners in rural communities, with little focus on
      regional centres or medical specialists.What does this study add? Rural origin is
      associated with regional centre recruitment. Professional, social and locational
      factors are all moderately important in both recruitment and retention.
      Specialist medical training for regional centres ideally requires both generalist
      and subspecialist skills sets. Workforce policy needs to address modifiable
      factors with four groups, namely commonwealth and state governments, specialist
      medical colleges and local communities, all needing to align their activities for
      achievement of long-term medical workforce outcomes.What are the implications for
      practitioners? Modifiable factors affecting recruitment and retention must be
      addressed to support specialist models of care in regional centres. Modifiable
      factors relate to maintenance of a critical mass of practitioners, training a fit
      for-purpose workforce and coordinated effort between stakeholders. Although
      remuneration is important, the decision to stay relates primarily to non
      financial factors.

PMID- 29190454
TI  - Phenolic metabolites from Hypericum kelleri Bald., an endemic species of Crete
      (Greece).
AB  - Thirteen compounds were isolated from the aerial parts of Hypericum kelleri
      Bald., growing as an endemic on the island of Crete (Greece). These compounds
      comprise four previously unknown prenylated xanthones 1,2-dihydro-3,8-dihydroxy-6
      methoxy-1,1,5-tri(3-methylbut-2-enyl)xanthen-2,9-dione (kellerine A), 1,2-dihydro
      3,6,8-trihydroxy-1,1,5-tri(3-methylbut-2-enyl)xanthen-2,9-dione (kellerine B),
      1,2-dihydro-3,8-dihydroxy-6-methoxy-1,1-bi(3-methylbut-2-enyl)xanthen-2,9-dione
      (6-methylpatulone), (R/S)-1,3,5-trihydroxy-2-(3-methyl-2-buten-1-yl)-4-[2-(3
      methylbut-2-enyl)-3-methylbut-3-enyl]-6-methoxy-9H-xanthen-9-one ((2"R/S)
      kellerine C) and the hitherto undescribed depsidone (R/S)-1,3,6-trihydroxy-5
      methoxy-2-(3-methyl-2-buten-1-yl)-4-[2-(3-methylbut-2-enyl)-3-methylbut-3-enyl]
      11Eta-dibenzo[b,e] [1,4]dioxepin-9-one ((2"R/S)-creticine). As known compounds,
      brevipsidone D, 4-geranyl-2-(2'-isobutyryl)-phloroglucinol, 4-geranyl-2-(2'
      methylbutyryl)-phloroglucinol, I3, II8-biapigenin, quercetin, avicularin,
      pseudohypericin and neochlorogenic acid have been isolated. The structures were
      elucidated on the basis of their 1D, 2D NMR, CD and MS data. The study confirms
      the typical occurrence of xanthones in Hypericum section Oligostema (Boiss.)
      Stef., and is also the first report on the simultaneous isolation of
      acylphloroglucinols in this section. Furthermore the first evidence of depsidones
      in the genus Hypericum L. is reported. Cytotoxicity was investigated in HeLa
      cells for prenylated xanthones and the depsidones. Both triprenylated 1,2
      dihydroxanthones (kellerine A and B) showed significant in vitro cytotoxicity
      with IC50 values of 2.5 +/- 0.1 (kellerine A) and 5.9 +/- 0.9 (kellerine B) MUM,
      whereas other compounds were less cytotoxic (IC50 > 20 MUM).

PMID- 29190455
TI  - Structural features of the salivary gland hypertrophy virus of the tsetse fly
      revealed by cryo-electron microscopy and tomography.
AB  - Glossina palipides salivary gland hypertrophy virus (GpSGHV) infects tsetse
      flies, which are vectors for African trypanosomosis. This virus represents a
      major challenge in insect mass rearing and has hampered the implementation of the
      sterile insect technique programs in the Member States of the International
      Atomic Energy Agency. GpSGHV virions consist of long rod-shaped particles over
      9000A in length, but little is known about their detailed structural
      organization. We show by cryo electron microscopy and cryo electron tomography
      that the GpSGHV virion has a unique, non-icosahedral helical structure. Its
      envelope exhibits regularly spaced spikes that protrude from the lipid bilayer
      and are arranged on a four-start helix. This study provides a detailed insight
      into the 3D architecture of GpSGHV, which will help to understand the viral life
      cycle and possibly allow the design of antiviral strategies in the context of
      tsetse fly infections.

PMID- 29190456
TI  - Aspects of the final phase of enamel formation as evidenced by observations of
      superficial enamel of human third molars using scanning electron microscopy.
AB  - OBJECTIVE: Enamel structure reflects ameloblast function. By studying the
      structure of the superficial enamel, information about ameloblast function toward
      the end of the secretory stage may be obtained. DESIGN: The superficial enamel in
      midcoronal areas of acid-etched facio-lingual sections from human third molars
      was studied in the scanning electron microscope (SEM). RESULTS: A great variation
      was observed in occurrence of prism-free enamel. Prism-free enamel dominated in
      40% (mandibular) and 47% (maxillary) of observed areas and had a mean thickness
      of about 30MUm. Striations in the prism-free enamel had an interstriae distance
      of about 3.3-3.8MUm. The angle between prisms and enamel surface was about 60
      degrees , between prisms and Retzius lines about 45 degrees  and between Retzius
      lines and enamel surface about 15 degrees . The distances between regularly
      occurring Retzius lines and between striations in the prism-free enamel both
      tended to decrease toward the enamel surface. Prisms could change direction as
      they approached the enamel surface, mostly in cervical direction. Where Retzius
      lines curved and converged occlusally, prisms tended to deviate in an occlusal
      direction. CONCLUSIONS: Judged from the incremental lines and occurrence of prism
      free enamel, ameloblasts slow down and tend to lose their Tomes' process as they
      approach the end of secretion. The crystals of prism-free enamel belong to the
      same system as the interprism crystals of prismatic enamel. A method, based on
      the disposition of fine incremental lines, is suggested for evaluation of
      ameloblast dynamics in the last stage of enamel secretion.

PMID- 29190457
TI  - The influence of the number of toys in the environment on toddlers' play.
AB  - We tested the hypothesis that an environment with fewer toys will lead to higher
      quality of play for toddlers. Each participant (n=36) engaged in supervised,
      individual free play sessions under two conditions: Four Toy and Sixteen Toy.
      With fewer toys, participants had fewer incidences of toy play, longer durations
      of toy play, and played with toys in a greater variety of ways (Z=-4.448,
      p<0.001, r=-0.524; Z=2.828, p=0.005, r=0.333; and Z=4.676, p<0.001, r=0.55,
      respectively). This suggests that when provided with fewer toys in the
      environment, toddlers engage in longer periods of play with a single toy,
      allowing better focus to explore and play more creatively. This can be offered as
      a recommendation in many natural environments to support children's development
      and promote healthy play.

PMID- 29190458
TI  - A Rare Cause of Left Upper Quadrant Abdominal Pain.

PMID- 29190459
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- 29190460
TI  - Clinical outcomes in older surgical patients with mild cognitive impairment.
AB  - INTRODUCTION: Older adults, including those with mild cognitive impairment (MCI),
      are increasingly undergoing surgery. METHODS: Relative risks (RRs) of MCI alone
      or with delirium on adverse outcomes were estimated in an ongoing prospective,
      observational cohort study of 560 nondemented adults aged >=70 years. RESULTS:
      MCI (n = 61, 11%) was associated with increased RR of delirium (RR = 1.9, P <
      .001) and delirium severity (RR = 4.6, P < .001). Delirium alone (n = 107), but
      not MCI alone (n = 34), was associated with multiple adverse outcomes including
      more major postoperative complication(s) (RR = 2.5, P = .002) and longer length
      of stay (RR = 2.2, P < .001). Patients with concurrent MCI and delirium (n = 27)
      were more often discharged to a postacute facility (RR = 1.4, P < .001) and had
      synergistically increased risk for new impairments in cognitive functioning (RR =
      3.6, P < .001). DISCUSSION: MCI is associated with increased risk of delirium
      incidence and severity. Patients with delirium and MCI have synergistically
      elevated risk of developing new difficulties in cognitively demanding tasks.

PMID- 29190461
TI  - Antimicrobial photodynamic therapy: Single-walled carbon nanotube (SWCNT)
      Porphyrin conjugate for visible light mediated inactivation of Staphylococcus
      aureus.
AB  - Due to the excessive use of antibiotics over the years, the microorganisms have
      developed resistance to numerous drugs. The growth of multi-resistant organisms
      (MROs) heads due to the insufficient treatment with the currently available
      medications which present a great threat to the biotic component of the
      environment as well as to the food technology sectors. The goal of this research
      was to develop a nano-composite made up of single-walled carbon nanotubes
      (SWCNTs) and amine-functionalized porphyrin, which could further be used for the
      anti-microbial studies in presence of visible light showing photodynamic effect
      to inactivate cells. Photodynamic antimicrobial chemotherapy is gaining
      significant interest due to its capabilities as an innovative form of
      antimicrobial treatment. The development of anti-microbial photodynamic therapy
      (a-PDT) is a non-antibiotic access to inactivate microorganisms. We examined the
      synthesis of amine-functionalized porphyrin and conjugated it to the oxidised
      single-walled carbon nanotubes (SWCNTs). By the use of appropriate amount of
      single-walled carbon nanotubes (SWCNTs), we have shown the interaction between
      the porphyrin conjugated nanotubes and the bacterial cells in presence of visible
      light led to the cell membrane damage, concluding that SWCNT-porphyrin conjugates
      can be used as an antibacterial agent. The characterization of the oxidised SWCNT
      and SWCNT-porphyrin conjugates was determined by field emission scanning electron
      microscopy (FE-SEM), which provides detailed information about the composition
      and the morphological analysis. The particle size measurements were carried out
      by transmission electron microscopy (TEM). On investigating under the florescence
      microscopy, red fluorescence was observed. Thus, these properties demand us to
      design this facile material comprised of SWCNT-aminoporphyrin conjugates that
      shows potent antibacterial activity.

PMID- 29190462
TI  - Etching and anti-etching strategy for sensitive colorimetric sensing of H2O2 and
      biothiols based on silver/carbon nanomaterial.
AB  - In this paper, the colorimetric sensing of H2O2 related molecules and biothiols
      based on etching and anti-etching strategy was firstly proposed. Ag/carbon
      nanocomposite (Ag/C NC) was served as the sensing nanoprobe, which was
      synthesized via carbon dots (C-dots) as the reductant and stabilizer. The
      characteristic surface plasmon resonance (SPR) absorbance of Ag nanoparticles
      (AgNPs) was sensitive to the amount of hydrogen peroxide (H2O2). It exhibited
      strong optical responses to H2O2 with the solution colour changing from yellow to
      nearly colourless, which is resulted from the etching of Ag by H2O2. The sensing
      platform was further extended to detect H2O2 related molecules such as lactate in
      coupling with the specific catalysis oxidation of L-lactate by lactate oxidase
      (LOx) and formation of H2O2. It provides wide linear range for detecting H2O2 in
      0.1-80MUM and 80-220MUM with the detection limit as low as 0.03MUM (S/N=3). In
      the presence of biothiols, the etching from the H2O2 can be hampered. Other
      biothiols exhibit anti-etching effects well. The strategy works well in detecting
      of typical biothiols including cysteine (Cys), homocysteine (Hcy) and glutathione
      (GSH). Thus, a simple colorimetric strategy for sensitive detection of H2O2 and
      biothiols is proposed. It is believed that the colorimetric sensor based on
      etching and anti-etching strategy can be applied in other systems in chemical and
      biosensing areas.

PMID- 29190463
TI  - Genipin-treated chitosan nanofibers as a novel scaffold for nerve guidance
      channel design.
AB  - Schwann cell-seeded nerve guidance channels are designed to assist post-traumatic
      nerve regeneration in the PNS. Chitosan is a natural polymer well suited for
      tissue engineering as it is biocompatible, non-immunogenic, and biodegradable.
      Electrospun chitosan nanofibers utilized in nerve guidance channels have the
      capacity for guiding axonal growth within the channel lumen yet are limited in
      their capacity to maintain structural integrity within physiological
      environments. To address this, we attempted genipin crosslinking of chitosan
      nanofibers. Compared to neat chitosan nanofibers, genipin-treated nanofibers
      exhibited increased stiffness, resistance to swelling and lysozymal degradation.
      Furthermore, alignment and proliferation of purified Schwann cell cultures upon
      genipin-treated substratum was enhanced. When dorsal root ganglion explants were
      utilized as an in vitro model of peripheral nerve regeneration, emigrating
      neurons and Schwann cells assumed the uniaxial pattern of aligned electrospun
      chitosan nanofibers. Neurite growth along the nanofibers led, reaching a frontier
      more than twice that of the pursuant Schwann cells. Critically, neurite growth
      rate upon genipin-treated nanofibers demonstrated a 100% increase. Altogether,
      genipin treatment improves upon the physical and biological properties of
      chitosan nanofibers towards their utility in nerve guidance channel design.

PMID- 29190464
TI  - Facile one-pot fabrication of calcium phosphate-based composite nanoparticles as
      delivery and MRI contrast agents for macrophages.
AB  - We developed a facile one-pot fabrication process for magnetic iron oxide-calcium
      phosphate (IO-CaP) composite nanoparticles via coprecipitation in labile
      supersaturated CaP solutions containing IO nanocrystals. All the source solutions
      used were clinically approved for injection, including water and magnetic IO
      nanocrystals (ferucarbotran, used as a negative magnetic resonance imaging (MRI)
      contrast agent). This ensured that the resulting nanoparticles were pathogen- and
      endotoxin-free. The dispersants used were clinically approved heparin sodium
      (heparin) or adenosine triphosphate disodium hydrate (ATP), which were added to
      the IO-containing labile supersaturated CaP solutions. Both heparin and ATP
      coprecipitated with CaP and ferucarbotran to form heparin- and ATP-modified IO
      CaP nanoparticles, respectively, with a hydrodynamic diameter of a few hundred
      nanometers. Both the resulting nanoparticles exhibited relatively large negative
      zeta potentials, caused by the negatively charged functional groups in heparin
      and ATP, which improved the particle dispersibility when compared to non-modified
      IO-CaP nanoparticles. The heparin-modified IO-CaP nanoparticles were effectively
      ingested by murine macrophages (RAW264.7) without showing significant
      cytotoxicity but barely ingested by non-phagocytotic human umbilical vein
      endothelial cells, indicating the potential of these nanoparticles for targeted
      delivery to macrophages. The heparin-modified IO-CaP nanoparticles exhibited a
      negative contrast enhancing ability for MRI. Our results show that IO-CaP
      nanoparticles have potential as delivery and MRI contrast agents for macrophages.

PMID- 29190465
TI  - RNA purification from Escherichia coli cells using boronated nanoparticles.
AB  - Boronate affinity chromatography is a common purification method used for
      isolation and purification of cis-diol containing biomolecules. Poly
      (hydroxyethyl methacrylate-co-vinyl phenyl boronic acid) [P(HEMA-VPBA)]
      nanoparticles were prepared by miniemulsion polymerization to use in RNA
      purification methods. The P(HEMA-VPBA) nanoparticles were characterized by
      particle size distribution, surface area, Fourier transform infrared spectroscopy
      and atomic force microscopy. The effects of temperature, pH, RNA concentration
      and different salt types on RNA binding on the P(HEMA-VPBA) nanoparticles were
      examined. It was observed that RNA binding was increased with the increasing of
      pH and max RNA binding was obtained at pH 9.0. RNA binding capacity of the P(HEMA
      VPBA) nanoparticles was increased from 167mg/g to 601mg/g with addition of BaCl2
      to the binding medium. Maximum RNA binding capacity of the P(HEMA-VPBA)
      nanoparticles was 172mg/g at 1.0mg/mL initial RNA concentration. The P(HEMA-VPBA)
      nanoparticles were reusable for RNA binding. RNA was also extracted from
      Escherichia coli cells and purified successfully using the P(HEMA-VPBA)
      nanoparticles.

PMID- 29190466
TI  - Thermo-responsive molecularly imprinted polymer containing magnetic
      nanoparticles: Synthesis, characterization and adsorption properties for
      curcumin.
AB  - A novel intelligent thermoresponsive-magnetic molecularly imprinted polymer
      (TMMIP) nanocomposite based on N-isopropylacrylamide (NIPAM) & Fe3O4 was designed
      for the controlled & sustained release of Curcumin (CUR) with the ability to
      response external stimulus. The TMMIP nanocomposite was prepared using acryl
      functionalized beta-cyclodextrin (beta-CD) and NIPAM as functional monomers and
      CUR as target molecule. The recognition cavities which caused by host-guest
      interactions had direct influence to enhanced drug loading and sustained release
      of CUR. According to in-vitro release experiment in two different temperatures
      (below & above LCST of NIPAM) the prolonged & controlled release of CUR were
      observed. The release rate could be controlled by changing the temperature
      because of the phase transition behavior of NIPAM monomer. Also, the proposed
      biosensor displayed effective role in separation science, reasonable adsorption
      capacity (77mgg-1), fast recognition (10min equilibration), selective extraction
      toward CUR in the presence of structural analogues and easily separation using
      external magnetic field. Moreover, the synthesized TMMIP was confirmed by various
      characterization.

PMID- 29190467
TI  - pH sensitive surfactant-stabilized Fe3O4 magnetic nanocarriers for dual drug
      delivery.
AB  - Highly water-dispersible surfactant-stabilized Fe3O4 magnetic nanocarriers
      (SMNCs) were prepared by self-assembly of anionic surfactant, sodium dodecyl
      sulphate (SDS) on hydrophobic (oleic acid coated) nanoparticles and their
      biomedical applications were investigated. These nanocarriers have an average
      size of about 10nm and possess tunable surface charge properties. The formation
      of an organic coating of SDS was evident from infrared spectroscopy, dynamic
      light scattering, zeta-potential and thermogravimetric measurements. These
      nanocarriers were used for loading of both hydrophilic and hydrophobic anticancer
      agents such as doxorubicin hydrochloride (DOX) and curcumin (CUR), respectively.
      DOX was conjugated onto the surface of nanocarriers through electrostatic
      interaction, whereas CUR was encapsulated into the hydrophobic interlayer between
      oleic acid and SDS. The toxicity and cellular internalization of drug loaded
      nanocarriers were investigated against WEHI-164 cancer cell line. Specifically,
      the drug loading, pH sensitive drug release and cellular internalization studies
      suggested that these nanocarriers are suitable for dual drug delivery.
      Furthermore, they show good heating ability under AC magnetic field, thus can be
      used as effective heating source for hyperthermia treatment of cancer.

PMID- 29190468
TI  - Selenoprotein L-inspired nano-vesicular peroxidase mimics based on amphiphilic
      diselenides.
AB  - In this study, we developed selenoprotein L-inspired nano-vesicular peroxidase
      mimics based on amphiphilic diselenides. Selenocystine (SeCyst) was used as the
      starting material for the synthesis of four liposomal membrane-compatible
      diselenide derivatives (R-Se-Se-R') with two hydrophobic tails and a polar part.
      The diselenide derivatives were successfully incorporated into the
      phosphatidylcholine (PC)-based nano-vesicular scaffold. The results of the
      particle diameter and zeta-potential measurements suggested that the functional
      diselenide moiety was placed around the outer surface, not in the hydrophobic
      interior, of the liposomal membrane structures. The GPx-like catalytic activity
      of the diselenide/PC liposomes was determined by the conventional NADPH method
      using glutathione as the reducing substrate. For three peroxide substrates, i.e.,
      hydrogen peroxide, organic tert-butyl hydroperoxide and cummen hydroperoxide, the
      cationic property-possessing diselenide derivatives in the PC-based liposomes
      resulted in a higher catalytic activity in comparison to electrically neutral and
      anionic derivatives. Overall, the diselenide derivatives at the surface of a
      liposomal colloidal scaffold could exert a GPx-like catalytic activity in
      physiological aqueous media.

PMID- 29190469
TI  - Effects of solution chemistry on the sunlight inactivation of particles
      associated viruses MS2.
AB  - The inactivation efficacy of bacteriophage MS2 by simulated sunlight irradiation
      was investigated to understand the effects of MS2 aggregation and adsorption to
      particles in solutions with different components. Kaolinite and Microcystis
      aeruginosa were used as model inorganic and organic particles, respectively.
      Lower pH and di-valent ions (Ca2+) were main factors on the aggregation and
      inactivation of MS2. In the presence of both particles, there was no significant
      impact on the MS2 inactivation efficacy by kaolinite (10-200mM) or Microcystis
      aeruginosa (102-105Cells/mL) in 1mM NaCl at pH 7. However at lower pH 3, MS2
      aggregates formed in the particle-free and kaolinite-containing solutions, caused
      lower inactivation since the outer viruses of aggregation protect the inner
      viruses. In addition, more MS2 adsorbed on Microcystis aeruginosa at lower pH (3
      and 4). Microcystis aeruginosa would act as a potential photosensitizer for ROS
      production to inactivate the adsorbed MS2, since extracellular organic matter
      (EOM) of Microcystis aeruginosa was detected in this study, which has been
      reported to produce ROS under solar irradiation. At pH 7, Na+ had no effect on
      the inactivation of MS2, because MS2 was stable and dispersed even at 200mM Na+.
      MS2 aggregated and adsorbed on particles even at 10mM Ca2+ and led to lower
      inactivation. Kaolinite cannot offer enough protection to adsorbed MS2 as
      aggregation and Microcystis aeruginosa acts as potential photosensitizer to
      produce ROS and inactivate the adsorbed MS2 at high concentration of Ca2+. In
      particle-free solution, SRNOM inhibited MS2 inactivation by shielding the
      sunlight and coating MS2 to increase its survival.

PMID- 29190470
TI  - Negatively charged polypeptide-peptide nanoparticles showing efficient drug
      delivery to the mitochondria.
AB  - Polymeric nanoparticles (NPs) represent an effective platform for drug delivery
      systems, albeit with various limitations including low drug loading capacity,
      cytotoxicity and specificity. NPs composed of the negatively charged Polypeptide,
      poly gamma glutamic acid (gamma-PGA) and a designed amphiphilic and cationic beta
      sheet Peptide (denoted PoP-NPs) loaded with the drug lonidamine (LND), denoted
      LND-PoP-NPs were previously used in our lab to successfully target the
      mitochondria when coated with the peptide (LND-mPoP-NPs). In this study, we
      improved the drug capacity of the LND-mPoP-NPs in addition to lowering non
      specific toxicity associated with the drug deficient mPoP-NPs. LND concentrations
      in LND-mPoP-NPs were increased (h-LND-mPoP-NPs) and the peptide coating
      concentration was decreased. The new h-LND-mPoP-NPs formulation shows the ability
      to carry the drug to the proximity of the mitochondria despite the NP's negative
      zeta potential.

PMID- 29190471
TI  - Influence of shape and dispersion media of titanium dioxide nanostructures on
      microvessel network and ossification.
AB  - Titanium dioxide nanoparticles (TiO2 NPs) production has been used for pigment,
      food and cosmetic industry and more recently, shaped as belts for treatment of
      contaminated water, self-cleaning windows and biomedical applications. However,
      the toxicological data have demonstrated that TiO2 NPs inhalation induce
      inflammation in in vivo models and in vitro exposure leads to cytotoxicity and
      DNA damage. Dermal exposure has limited adverse effects and the possible risks
      for implants used for tissue regeneration is still under research. Then, it has
      been difficult to establish a straight statement about TiO2 NPs toxicity since
      route of exposure and shapes of nanoparticles play an important role in the
      effects. In this study we aimed to investigate the effect of three different
      types of TiO2 NPs (industrial, food-grade and belts) dispersed in fetal bovine
      serum (FBS) and saline solution (SS) on microvessel network, angiogenesis gene
      expression and femur ossification using a chick embryo model after an acute
      exposure of NPs on the day 7 after eggs fertilization. Microvascular density of
      chorioallantoic membrane (CAM) was analyzed after 7days of NPs injection and
      vehicles induced biological effects per se. NPs dispersed in FBS or SS have
      slight differences in microvascular density, mainly opposite effect on
      angiogenesis gene expression and no effects on femur ossification for NPs
      dispersed in SS. Interestingly, NPs shaped as belts dramatically prevented the
      alterations in ossification induced by FBS used as vehicle.

PMID- 29190472
TI  - A fluorescent sensor for detecting dopamine and tyrosinase activity by dual
      emission carbon dots and gold nanoparticles.
AB  - In this work, we report a fluorescence strategy for detecting dopamine (DA) and
      sensing tyrosinase (TYR) activity on the basis of the dual-emission carbon dots
      (DECDs), which contain two emitters: the blue emitters (BE, maximum emission at
      385nm) and yellow emitters (YE, maximum emission at 530nm). Gold nanoparticles
      (AuNPs) can effectively quench the two emissions of DECDs. The addition of DA
      aggregates AuNPs effectively, leading to the fluorescence recovery of dual
      emitters gradually. This strategy exhibits a high selectivity toward DA and shows
      good linear ranges, such as 0.5-3MUM for BE and 0.1-3MUM for YE. Additionally,
      the proposed method is successfully applied to the determination of DA in real
      samples with satisfactory recoveries. Subsequently, this DECDs-AuNPs platform is
      further taken advantage to assess TYR activity by the aid of TYR's capability for
      oxidation of DA into dopaquinone, which will not induce the agglomeration of
      AuNPs, so the fluorescence quenching of DECDs is associated with TYR activity.
      Finally, the mechanism of the reaction is discussed in detail, and the results
      suggest that both amine and phenolic hydroxyl groups of DA bring the aggregation
      of AuNPs.

PMID- 29190473
TI  - Participation of copper ions in formation of alginate conditioning layer: Evolved
      structure and regulated microbial adhesion.
AB  - Antifouling function of copper-based layers is usually gained through the release
      of cuprous or copper ions to damage most fouling species. In this research the
      intervening mechanisms of copper ions in formation of simplified conditioning
      layer comprising marine polysaccharide alginate and subsequent adhesion of
      typical marine bacteria and algae were studied. Fast interaction of Cu2+ with
      alginate with the formation of copper alginate multimers was observed for the
      first time by negative-staining electron microscopy. Interconnecting chains of
      alginate and copper alginate upon adsorption on silicon wafer and tangled
      structure of the conditioning layer were further characterized by atomic force
      microscopy. Adhesion testing showed that consumption of copper ions by their
      linking with alginate in incubation solutions resulted in mitigated toxicity of
      the ions to the microorganisms Bacillus sp., Chlorella pyrenoidosa and
      Phaeodactylum tricornutum. The results would give insight into understanding and
      regulating the formation of conditioning layer for desired antifouling
      performances.

PMID- 29190474
TI  - Functional Micrococcus lysodeikticus layers deposited by laser technique for the
      optical sensing of lysozyme.
AB  - Whole cell optical biosensors, made by immobilizing whole algal, bacterial or
      mammalian cells on various supports have found applications in several fields,
      from ecology and ecotoxicity testing to biopharmaceutical production or medical
      diagnostics. We hereby report the deposition of functional bacterial layers of
      Micrococcus lysodeikticus (ML) via Matrix-Assisted Pulsed Laser Evaporation
      (MAPLE) on poly(diallyldimethylamonium) (PDDA)-coated-glass slides and their
      application as an optical biosensor for the detection of lysozyme in serum.
      Lysozyme is an enzyme upregulated in inflammatory diseases and ML is an enzymatic
      substrate for this enzyme. The MAPLE-deposited bacterial interfaces were
      characterised by Scanning Electron Microscopy (SEM), Atomic Force Microscopy
      (AFM), Fourier-Transformed Infrared Spectroscopy (FTIR), Raman and optical
      microscopy and were compared with control interfaces deposited via layer-by-layer
      on the same substrate. After MAPLE deposition and coating with graphene oxide
      (GO), ML-modified interfaces retained their functionality and sensitivity to
      lysozyme's lytic action. The optical biosensor detected lysozyme in undiluted
      serum in the clinically relevant range up to 10MUgmL-1, in a fast and simple
      manner.

PMID- 29190475
TI  - Discovery of microRNAs associated with the antiviral immune response of Atlantic
      cod macrophages.
AB  - MicroRNAs (miRNAs) are known to play important immunoregulatory roles in
      teleosts, although miRNAs involved in the antiviral immune response of Atlantic
      cod (Gadus morhua) were previously uncharacterised. Using deep sequencing and
      qPCR, the present study was conducted to identify miRNAs responsive to the viral
      mimic, polyriboinosinic polyribocytidylic acid (pIC) in Atlantic cod macrophages.
      Macrophage samples isolated from Atlantic cod (n=3) and treated with pIC or
      phosphate buffered saline (PBS control) for 24 and 72h were used for miRNA
      profiling. Following deep sequencing, DESeq2 analyses identified four (miR-731
      3p, miR-125b-3-3p, miR-150-3p and miR-462-3p) and two (miR-2188-3p and miR-462
      3p) significantly differentially expressed miRNAs at 24 and 72h post-stimulation
      (HPS), respectively. Sequencing-identified miRNAs were subjected to qPCR
      validation using a larger number of biological replicates (n=6) exposed to pIC or
      PBS over time (i.e. 12, 24, 48 and 72 HPS). As in sequencing, miR-731-3p, miR-462
      3p and miR-2188-3p showed significant up-regulation by pIC. The sequencing
      results were not qPCR-validated for miR-125b-3-3p and miR-150-3p as up- and down
      regulated miRNAs at 24 HPS, respectively; however, qPCR results showed
      significant up-regulation in response to pIC stimulation at later time points
      (i.e. 48 and/or 72 HPS). We also used qPCR to assess the expression of other
      miRNAs that were previously shown as immune responsive in other vertebrates. qPCR
      results at 48 and/or 72 HPS revealed that miR-128-3-5p, miR-214-1-5p and miR-451
      3p were induced by pIC, whereas miR-30b-3p and miR-199-1-3p expression were
      repressed in response to pIC. The present study identified ten pIC-stimulated
      miRNAs, suggesting them as important in antiviral immune responses of Atlantic
      cod macrophages. Some pIC-responsive miRNAs identified in this study were
      predicted to target putative immune-related genes of Atlantic cod (e.g. miR-30b
      3p targeting herc4), although the regulatory functions of these miRNAs need to be
      validated by future studies.

PMID- 29190476
TI  - The "Janus face" of the thrombin binding aptamer: Investigating the anticoagulant
      and antiproliferative properties through straightforward chemical modifications.
AB  - BACKGROUND: The thrombin binding aptamer (TBA) is endowed with both anticoagulant
      and antiproliferative activities. Its chemico-physical and/or biological
      properties can be tuned by the site-specific replacement of selected residues.
      METHODS: Four oligodeoxynucleotides (ODNs) based on the TBA sequence (5'
      GGTTGGTGTGGTTGG-3') and containing 2'-deoxyuridine (U) or 5-bromo-2'-deoxyuridine
      (B) residues at positions 4 or 13 have been investigated by NMR and CD
      techniques. Furthermore, their anticoagulant (PT assay) and antiproliferative
      properties (MTT assay) have been tested and compared with two further ODNs
      containing 5-hydroxymethyl-2'-deoxyuridine (H) residues in the same positions,
      previously investigated. RESULTS: The CD and NMR data suggest that all the
      investigated ODNs are able to form G-quadruplexes strictly resembling that of
      TBA. The introduction of B residues in positions 4 or 13 increases the melting
      temperature of the modified aptamers by 7  degrees C. The replacement of
      thymidines with U in the same positions results in an enhanced anticoagulant
      activity compared to TBA, also at low ODN concentration. Although all ODNs show
      antiproliferative properties, only TBA derivatives containing H in the positions
      4 and 13 lose the anticoagulant activity and remarkably preserve the
      antiproliferative one. CONCLUSIONS: All ODNs have shown antiproliferative
      activities against two cancer cell lines but only those with U and B are endowed
      with anticoagulant activities similar or improved compared to TBA. GENERAL
      SIGNIFICANCE: The appropriate site-specific replacement of the residues in the TT
      loops of TBA with commercially available thymine analogues is a useful strategy
      either to improve the anticoagulant activity or to preserve the antiproliferative
      properties by quenching the anticoagulant ones.

PMID- 29190477
TI  - Synthesis and biological evaluation of new oxopyrrolidine derivatives as
      inhibitors of acetyl cholinesterase and beta amyloid protein as anti -
      Alzheimer's agents.
AB  - A new series of oxopyrrolidines was synthesized and evaluated for their effect on
      Alzheimer's disease by measuring their inhibitory activity against acetyl
      cholinesterase enzyme and amyloid beta 42 protein. Most of the compounds showed
      good inhibitory activity with ethyl 2-(2-(2, 6-dimethylphenylcarbamoyl)- 5
      oxopyrrolidin-1-yl) acetate (V) having the highest activity against acetyl
      cholinesterase with IC50 value 1.84 ng/g tissue compared to standard donepezil
      3.34 ng/g tissue. Furthermore, compound 1-((4-(4-chlorophenyl) piperazin-1-yl)
      methyl)-N-(2,6-dimethylphenyl)-5- oxopyrrolidine- 2-carboxamide (IIIe) displayed
      the highest activity against beta 42 protein with IC50 value of 11.3 Pg/g tissue
      compared to 18.4 Pg/g tissue of donepezil.

PMID- 29190478
TI  - Sulfonamides containing curcumin scaffold: Synthesis, characterization, carbonic
      anhydrase inhibition and molecular docking studies.
AB  - Curcumin is a multi-functional pharmacologically safe natural agent with proven
      cytoprotective effects to healthy human cells. In this study, a new series of
      sulfonamides with curcumin scaffold were synthesized, characterized and
      investigated for their carbonic anhydrase isoenzyme I (human) and II (bovine)
      isoforms. The structures of newly synthesized compounds were described by IR, 1H
      NMR and 13C NMR spectral data. Compound 14 showed the Ki value of 0.99 uM with
      highest inhibitory activity among all other synthesized compounds against hCA-I
      enzyme. Similarly enzyme kinetic studies of compound 14, 16 and 30 against bCAII
      enzyme showed Ki values of 0.71, 0.67 and 0.71 uM respectively. Our biological
      assays results showed that most of active compounds have similar inhibitory
      activities compared to standard acetazolamide drug. The molecular docking
      predicted binding modes showed that these compounds bind with hCA-1 enzyme in
      similar fashion.

PMID- 29190480
TI  - Treatment of a highly-concentrated sulphate-rich synthetic wastewater using
      calcium hydroxide in a fluidised bed crystallizer.
AB  - This study aimed to investigate factors that affect the conversion of sulphates
      and magnesium, and the recovery of gypsum and magnesium hydroxide in the
      neutralization of a sulphate rich stream using calcium hydroxide, in a laboratory
      scale seeded fluidised bed crystallizer. Particular focus was on reducing the
      precipitated fines that escaped with the treated water, through the use of seeds,
      while removing as much sulphate-compounds from the waste stream as possible. The
      composition of the total sulphate salts was as follows: 80% magnesium sulphate,
      calcium sulphate remaining at its saturation concentration (1.5 g/L), with the
      remainder being sodium sulphate based on typical reverse osmosis retentate
      concentrations ranging from 1.5 - 120 g/L of total sulphate salts. The fluidised
      bed crystallizer, using silica seeds, was found to be effective at reducing the
      formation of gypsum and magnesium hydroxide fines by almost half. Feed
      concentrations of 35 g/L of total salts yielded better sulphate conversions (+/
      75%), compared to a feed concentration of 8 g/L (+/-30%). It was possible to
      remove 99% of the magnesium in the saline wastewater stream using a calcium to
      sulphate ratio of 1:1 for feed concentrations of 15 g/L and higher. Excess
      calcium hydroxide suspension improved sulphate conversions.

PMID- 29190481
TI  - A novel Fe-La-Ce tri-metallic composite for the removal of fluoride ions from
      aqueous media.

PMID- 29190482
TI  - Stropharia rugosoannulata and Gymnopilus luteofolius: Promising fungal species
      for pharmaceutical biodegradation in contaminated water.
AB  - Pharmaceuticals are environmental micropollutants that pose an emerging challenge
      because they are poorly eliminated in conventional wastewater treatment plants.
      Over the last decade, many attempts have been made to solve this problem, and
      wastewater fungal treatment is a promising alternative. In this study, six
      different ligninolytic fungi (Trametes versicolor, Ganoderma lucidum, Irpex
      lacteus, Stropharia rugosoannulata, Gymnopilus luteofolius and Agrocybe erebia)
      were studied as bioremediation candidates for the removal and degradation of six
      recalcitrant pharmaceutical micropollutants: Carbamazepine (CBZ), Venlafaxine
      (VFX), Iopromide (IPD), Diclofenac (DCF), Cyclophosphamide (CFD) and Ifosfamide
      (IFD). Self-immobilization in a pellet shape was achieved for all fungal mycelia
      (which was the first time that this was reported for S. rugosoannulata, G.
      luteofolius, and A. erebia). Biodegradation achievement was greater than 90% for
      IPD with G. luteofolius and greater than 70% for CBZ with S. rugosoannulata,
      which suggests a great potential for this alternative biological treatment.
      Besides, this was the first report where fungal treatment achieved CFD and IFD
      removals greater than 20% for the treatment with T. versicolor, G. lucidum and S.
      rugosoannulata.

PMID- 29190483
TI  - Eggshell membrane as a novel bio sorbent for remediation of boron from
      desalinated water.
AB  - This study investigated the use of eggshell membrane (ESM) as a bio-sorbent and
      the effect of temperature, pH, and initial concentration on its efficiency.
      Furthermore, by altering the chemical composition, modified eggshell membrane
      (MESM) was prepared, and its efficiency was compared with the ESM. Results showed
      that the adsorption of boron preferred an acidic condition; pH 6 at 35  degrees
      C. In addition, the positive value of DeltaH degrees  suggested that the reaction
      favored endothermic pathway, while the negative value for DeltaG degrees  further
      suggested that the adsorption process was spontaneous. Furthermore, the ESM could
      adsorb 97% of boron, while MESM was able to adsorb 95%. From the Fourier
      transform infrared (FTIR), different functional groups were recorded on the
      surface of the ESM and MESM, and they played key role in the boron adsorption
      mechanisms. Linear Freundlich model was suggested to best describe the
      experimental data with 99.4% correlation coefficient.

PMID- 29190484
TI  - A new biostimulation approach based on the concept of remaining P for soil
      bioremediation.
AB  - C:N:P ratio is generally adopted to estimate the amount of nitrogen and
      phosphorus to be added to soils to accelerate biodegradation of organic
      contaminants. However, differences in P fixation among soils lead to varying
      amounts of available P when a specific dose of the element is applied to
      different soils. Thus, the application of fertilizers to achieve a previously
      established C:P ratio leads to biodegradation rates that can be lower than the
      theoretical maximum. In this study, we developed an equation to estimate the dose
      of P required to maximize organic contaminant biodegradation in soils as a
      function of remaining P (P-rem), using diesel as a model contaminant. The soils
      were contaminated with diesel and received six doses of P. CO2 emission was used
      to estimate biodegradation of hydrocarbons. Biodegradation increased with P
      doses. The P level that provided the highest hydrocarbon biodegradation rate
      showed linear and negative correlation with P-rem. The result shows that the
      requirement for P decreases as the P-rem of the soil increases (or the P-fixing
      capacity decreases). The dose of P recommended to maximize hydrocarbon
      biodegradation rate in soil can be estimated by the formula P (mg/dm3) = 436.5
      5.39 * P-rem (mg/L).

PMID- 29190479
TI  - Recent progress on semiconducting polymer nanoparticles for molecular imaging and
      cancer phototherapy.
AB  - As a new class of organic optical nanomaterials, semiconducting polymer
      nanoparticles (SPNs) have the advantages of excellent optical properties, high
      photostability, facile surface functionalization, and are considered to possess
      good biocompatibility for biomedical applications. This review surveys recent
      progress made on the design and synthesis of SPNs for molecular imaging and
      cancer phototherapy. A variety of novel polymer design, chemical modification and
      nanoengineering strategies have been developed to precisely tune up
      optoelectronic properties of SPNs to enable fluorescence, chemiluminescence and
      photoacoustic (PA) imaging in living animals. With these imaging modalities, SPNs
      have been demonstrated not only to image tissues such as lymph nodes, vascular
      structure and tumors, but also to detect disease biomarkers such as reactive
      oxygen species (ROS) and protein sulfenic acid as well as physiological indexes
      such as pH and blood glucose concentration. The potentials of SPNs in cancer
      phototherapy including photodynamic and photothermal therapy are also highlighted
      with recent examples. Future efforts should further expand the use of SPNs in
      biomedical research and may even move them beyond pre-clinical studies.

PMID- 29190485
TI  - Removing the residual cellulase by graphene oxide to recycle the bio-polishing
      effluent for dyeing cotton fabrics.
AB  - In this research, a stable graphene oxide (GO) suspension was prepared by
      chemical reduction method from graphite powder. By TEM, the irregular GO sheets
      with single-atom-layered structure could be observed. The zeta potentials
      measurement indicated the surface charges of GO were strongly related to pH. BET
      analysis showed the GO had a specific surface area of 30.7 m2/g and pore volume
      of 0.10 cm3/g. When the GO was used to remove the residual cellulase in bio
      polishing effluent, it was found the removal capacity reached its maximum value
      at the pH 4-5. The kinetics studies showed that the removal process of cellulase
      followed a pseudo-second-order kinetic model with a rate constant (k2) of 0.276 *
      10-3 g/mg min and equilibrium adsorption capacity of 278.55 mg/g, respectively.
      By plotting the adsorption isotherms, it was found the Langmuir model fitted the
      experimental data well with a cellulase adsorption capacity of 574.71 mg/g,
      indicating the adsorption of cellulase by GO in a monolayer manner. When dyeing
      the cotton fabrics with reactive dyes, it was found that the cotton fabrics could
      acquire similar color properties in the recycled bio-polishing effluent as in
      fresh water, meaning the effectiveness of removing cellulase by GO and the
      feasibility of recycling the bio-polishing effluent.

PMID- 29190486
TI  - Under pressure: Evaluating the role of intraoperative hemodynamics in
      postoperative acute kidney injury.

PMID- 29190487
TI  - Minimally invasive laser vibrometry (MIVIB) with a floating mass transducer - A
      new method for objective evaluation of the middle ear demonstrated on stapes
      fixation.
AB  - Ossicular fixation through otosclerosis, chronic otitis media and other
      pathologies, especially tympanosclerosis, are treated by surgery if hearing aids
      fail as an alternative. However, the best hearing outcome is often based on
      knowledge of the degree and location of the fixation. Objective methods to
      quantify the degree and position of the fixation are largely lacking. Laser
      vibrometry is a known method to detect ossicular fixation but clinical
      applicability remains limited. A new method, minimally invasive laser vibrometry
      (MIVIB), is presented to quantify ossicle mobility using laser vibrometry
      measurement through the ear canal after elevating the tympanic membrane, thus
      making the method feasible in minimally invasive explorative surgery. A floating
      mass transducer provides a clinically relevant transducer to drive ossicular
      vibration. This device was attached to the manubrium and drove vibrations at the
      same angle as the longitudinal axis of the stapes and was therefore used to
      assess ossicular chain mobility in a fresh-frozen temporal bone model with and
      without stapes fixation. The ratio between the umbo and incus long process was
      shown to be useful in assessing stapes fixation. The incus-to-umbo velocity ratio
      decreased by 15 dB when comparing the unfixated situation to stapes fixation up
      to 2.5 kHz. Such quantification of ossicular fixation using the incus-to-umbo
      velocity ratio would allow quick and objective analysis of ossicular chain
      fixations which will assist the surgeon in surgical planning and optimize hearing
      outcomes.

PMID- 29190488
TI  - The effect of simulated unilateral hearing loss on horizontal sound localization
      accuracy and recognition of speech in spatially separate competing speech.
AB  - Unilateral hearing loss (UHL) occurs in 25% of cases of congenital sensorineural
      hearing loss. Due to the unilaterally reduced audibility associated with UHL,
      everyday demanding listening situations may be disrupted despite normal hearing
      in one ear. The aim of this study was to quantify acute changes in recognition of
      speech in spatially separate competing speech and sound localization accuracy,
      and relate those changes to two levels of temporary induced UHL (UHL30 and UHL43;
      suffixes denote the average hearing threshold across 0.5, 1, 2, and 4 kHz) for 8
      normal-hearing adults. A within-subject repeated-measures design was used (normal
      binaural conditions, UHL30 and UHL43). The main outcome measures were the
      threshold for 40% correct speech recognition and the overall variance in sound
      localization accuracy quantified by an Error Index (0 = perfect performance, 1.0
      = random performance). Distinct and statistically significant deterioration in
      speech recognition (2.0 dB increase in threshold, p < 0.01) and sound
      localization (Error Index increase of 0.16, p < 0.001) occurred in the UHL30
      condition. Speech recognition did not significantly deteriorate further in the
      UHL43 condition (1.0 dB increase in speech recognition threshold, p > 0.05),
      while sound localization was additionally impaired (Error Index increase of 0.33,
      p < 0.01) with an associated large increase in individual variability.
      Qualitative analyses on a subject-by-subject basis showed that high-frequency
      audibility was important for speech recognition, while low-frequency audibility
      was important for horizontal sound localization accuracy. While the data might
      not be entirely applicable to individuals with long-standing UHL, the results
      suggest a need for intervention for mild-to-moderate UHL.

PMID- 29190489
TI  - Critical role of top-down processes and the push-pull mechanism in semantic
      single negative priming.
AB  - The present study investigated the roles of bottom-up mask-triggered inhibition
      and top-down inhibition in semantic categorization using the single negative
      priming (NP) paradigm. The masking (bottom-up) and ignore instructions (top-down,
      i.e., instructing participants to ignore the primes) were manipulated in
      Experiments 1-3 and Experiment 4, respectively. No priming was observed when only
      the masking was manipulated (Experiments 2 and 3), but NP was observed when a
      possible top-down ignore strategy (Experiment 1) or an ignore instruction
      (Experiment 4) was added. The results indicate that bottom-up mask-triggered
      inhibition cannot elicit semantic single NP by itself. However, top-down
      inhibition from an ignore instruction or ignore strategy is critical for
      triggering reliable semantic single NP. The findings suggest that semantic single
      NP originates from a push-pull mechanism by facilitating responses to unrelated
      trials and inhibiting responses to related trials. The experimental evidence also
      suggests that unconscious processes can be modulated by top-down control.

PMID- 29190490
TI  - Legionella quorum sensing and its role in pathogen-host interactions.
AB  - Legionella pneumophila is a water-borne opportunistic pathogen causing a life
      threatening pneumonia called 'Legionnaires' disease'. The Legionella quorum
      sensing (Lqs) system produces and responds to the alpha-hydroxyketone signaling
      molecule 3-hydroxypentadecane-4-one (Legionella autoinducer-1, LAI-1). The Lqs
      system controls the switch between the replicative/non-virulent and the
      transmissive/virulent phase of L. pneumophila, and it is a major regulator of
      natural competence, motility and virulence of the pathogen. Yet, beyond gene
      regulation, LAI-1 also directly affects pathogen-host interactions, since the
      signaling molecule modulates the migration of eukaryotic cells. Genes encoding
      Lqs homologues are present in many environmental bacteria, suggesting that alpha
      hydroxyketone signaling is widely used for inter-bacterial as well as inter
      kingdom signaling. In this review we summarize recent advances on the
      characterization of the Lqs system and its role in L. pneumophila-host cell
      interactions.

PMID- 29190491
TI  - Lipid metabolism and its implication in mycobacteria-host interaction.
AB  - The complex lipids present in the cell wall of Mycobacterium tuberculosis (Mtb)
      act as major effector molecules that actively interact with the host, modulating
      its metabolism and stimulating the immune response, which in turn affects the
      physiology of both, the host cell and the bacilli. Lipids from the host are also
      nutrient sources for the pathogen and define the fate of the infection by
      modulating lipid homeostasis. Although new technologies and experimental models
      of infection have greatly helped understanding the different aspects of the host
      pathogen interactions at the lipid level, the impact of this interaction in the
      Mtb lipid regulation is still incipient, mainly because of the low background
      knowledge in this area of research.

PMID- 29190492
TI  - Determinants for Effective ALECSAT Immunotherapy Treatment on Autologous Patient
      Derived Glioblastoma Stem Cells.
AB  - Glioblastoma (GBM) is the most aggressive primary brain tumor with a median
      survival of less than 15 months, emphasizing the need for better treatments.
      Immunotherapy as a treatment for improving or aiding the patient's own immune
      defense to target the tumor has been suggested for GBM. A randomized clinical
      trial of adoptive cell transfer using ALECSAT (Autologous Lymphoid Effector Cells
      Specific Against Tumor Cells) is currently ongoing in Sweden. Here we performed a
      paired pre-clinical study to investigate the composition and in vitro effect of
      ALECSAT and identify determinants for the effect using autologous GBM-derived
      cancer stem cells (CSC), immunocytochemistry and flow cytometry. We show a clear
      dose-response relationship of ALECSAT on CSC, suggesting that the number of
      infused cells is of importance. In addition, the in vitro effect of ALECSAT on
      CSC correlated significantly to the blood count of T helper (Th) cells in the
      patient indicating a potential benefit of collecting cells for ALECSAT
      preparation at an even earlier stage when patients generally have a better blood
      count. The factors identified in this study will be important to consider in the
      design of future immunotherapy trials to achieve prolonged survival.

PMID- 29190495
TI  - Global Uniform Asymptotic Fixed Deviation Stability and Stability for Delayed
      Fractional-order Memristive Neural Networks with Generic Memductance.
AB  - In this paper, we study global uniform asymptotic fixed deviation stability and
      stability for a wide class of memristive neural networks with time-varying
      delays. Firstly, a new mathematical expression of the generic memductance
      (memristance) is proposed according to the feature of the memristor and the
      general current-voltage characteristic and a new class of neural networks is
      designed. Next, a new concept of stability (fixed deviation stability) is
      proposed in order to describe veritably the stability characteristics of the
      discontinuous system and the sufficient conditions are given to guarantee the
      global uniform asymptotic fixed deviation stability and stability of the new
      system. Finally, two numerical examples are provided to show the applicability
      and effectiveness of our main results.

PMID- 29190493
TI  - BIGH3 Promotes Osteolytic Lesions in Renal Cell Carcinoma Bone Metastasis by
      Inhibiting Osteoblast Differentiation.
AB  - BACKGROUND: Bone metastasis is common in renal cell carcinoma (RCC), and the
      lesions are mainly osteolytic. The mechanism of bone destruction in RCC bone
      metastasis is unknown. METHODS: We used a direct intrafemur injection of mice
      with bone-derived 786-O RCC cells (Bo-786) as an in vivo model to study if
      inhibition of osteoblast differentiation is involved in osteolytic bone lesions
      in RCC bone metastasis. RESULTS: We showed that bone-derived Bo-786 cells induced
      osteolytic bone lesions in the femur of mice. We examined the effect of
      conditioned medium of Bo-786 cells (Bo-786 CM) on both primary mouse osteoblasts
      and MC3T3-E1 preosteoblasts and found that Bo-786 CM inhibited osteoblast
      differentiation. Secretome analysis of Bo-786 CM revealed that BIGH3 (Beta ig h3
      protein), also known as TGFBI (transforming growth factor beta-induced protein),
      is highly expressed. We generated recombinant BIGH3 and found that BIGH3
      inhibited osteoblast differentiation in vitro. In addition, CM from Bo-786 BIGH3
      knockdown cells (786-BIGH3 KD) reduced the inhibition of osteoblast
      differentiation compared to CM from vector control. Intrafemural injection of
      mice with 786-BIGH3 KD cells showed a reduction in osteolytic bone lesions
      compared to vector control. Immunohistochemical staining of 18 bone metastasis
      specimens from human RCC showed strong BIGH3 expression in 11/18 (61%) and
      moderate BIGH3 expression in 7/18 (39%) of the specimens. CONCLUSIONS: These
      results suggest that suppression of osteoblast differentiation by BIGH3 is one of
      the mechanisms that enhance osteolytic lesions in RCC bone metastasis, and raise
      the possibilty that treatments that increase bone formation may improve therapy
      outcomes.

PMID- 29190494
TI  - FUS-CHOP Promotes Invasion in Myxoid Liposarcoma through a SRC/FAK/RHO/ROCK
      Dependent Pathway.
AB  - Deregulated SRC/FAK signaling leads to enhanced migration and invasion in many
      types of tumors. In myxoid and round cell liposarcoma (MRCLS), an adipocytic
      tumor characterized by the expression of the fusion oncogene FUS-CHOP, SRC have
      been found as one of the most activated kinases. Here we used a cell-of-origin
      model of MRCLS and an MRCLS cell line to thoroughly characterize the mechanisms
      of cell invasion induced by FUS-CHOP using in vitro (3D spheroid invasion assays)
      and in vivo (chicken chorioallantoic membrane model) approaches. FUS-CHOP
      expression activated SRC-FAK signaling and increased the invasive ability of
      MRCLS cells. In addition, FAK expression was found to significantly correlate
      with tumor aggressiveness in sarcoma patient samples. The involvement of SRC/FAK
      activation in FUS-CHOP-mediated invasion was further confirmed using the SRC
      inhibitor dasatinib, the specific FAK inhibitor PF-573228, and FAK siRNA.
      Notably, dasatinib and PF573228 could also efficiently block the invasion of
      cancer stem cell subpopulations. Downstream of SRC/FAK signaling, we found that
      FUS-CHOP expression increases the levels of the RHO/ROCK downstream effector
      phospho-MLC2 (T18/S19) and that this activation was prevented by dasatinib or
      PF573228. Moreover, the ROCK inhibitor RKI-1447 was able to completely abolish
      invasion in FUS-CHOP-expressing cells. These data uncover the involvement of
      SRC/FAK/RHO/ROCK signaling axis in FUS-CHOP-mediated invasion, thus providing a
      rationale for testing inhibitors of this pathway as potential novel
      antimetastatic agents for MRCLS treatment.

PMID- 29190496
TI  - Rerouting mesenchymal stem cell trajectory towards epithelial lineage by
      engineering cellular niche.
AB  - Mesenchymal stromal/stem cells (MSCs) are multipotent cells that offer a
      promising outcome in the field of regenerative medicine. MSCs are present in
      various tissues including bone marrow, fat, skin, and placenta. The interest in
      clinical application of these mesoderm-derived MSCs is primarily fueled by their
      high self-renewal capacity and multipotency. Although, early studies indicated
      limited differentiation capacity of MSCs into same cell lineages from which they
      were isolated, subsequent investigations showed differentiation potential into
      other cell types of mesoderm origin including osteoblasts, adipocytes,
      fibroblasts, cardiomyocytes, and chondrocytes. Furthermore, MSCs exhibit a
      remarkable feature of transdifferentiation into ectodermal, neuroectodermal, and
      endodermal cells, phenomena referred to as 'stem cell plasticity'. This opened
      the possibility of clinical applications of MSCs in the regeneration of other
      tissues like corneal reconstruction, treatment of acute lung injury, oral mucosal
      regeneration, homing of MSCs for regeneration at sites of injury etc. Though
      several evidence have accrued demonstrating this phenomenon, there is still a gap
      in understanding the molecular mechanism of such transitions which will be
      important to efficiently control the process. Interestingly, the process can be
      drawn a parallel with the Mesenchymal to Epithelial Transitions (MET) that takes
      place inside the body during embryonic development or certain pathophysiological
      conditions. In this review, a brief attempt is first made to understand the
      evidence of MSC transdifferentiation based on the current knowledge about MET. We
      then specifically focus on systematic presentation and analysis of the
      microenvironment factors involved in MSC transdifferentiation to epithelial
      lineages which would have applications in regenerative medicine.

PMID- 29190497
TI  - Red blood cell-like particles with the ability to avoid lung and spleen
      accumulation for the treatment of liver fibrosis.
AB  - Micro-sized drug-carrier particles accumulate mainly in the lungs and nano-sized
      particles tend to accumulate in the liver and spleen. Here, we show that micro
      particles designed to mimic red blood cells (RBCs) can overcome these
      limitations. The RBC-MPs created in this study have a unique intra-particle
      elasticity distribution (IED), enabling them to bend around the central axis of
      the RBC-like dent, enabling them to pass through pores smaller than their
      diameter, mechanically behaving as authentic RBCs. In contrast, spherical MPs
      (SPH-MPs) and RBC-MPs hardened by incorporating a siloxane network (SiO2-RBC
      MPs), could not. In addition to the IED, we discovered that the deformability
      also depends on the shape and average particle elasticity. RBC-MPs did not
      accumulate in the lungs and the spleen, but were targeted specifically to the
      liver instead. In contrast, non-RBC-MPs such as SPH-MPs and SiO2-RBC-MPs showed
      heavy accumulation in the lungs and/or spleen, and were dispersed non
      specifically in various organs. Thus, controlling the shape and mechanical
      properties of RBC-MPs is important for achieving the desired biodistribution.
      When RBC-MPs were loaded with a (TGF)-beta receptor inhibitor, RBC-MPs could
      treat liver fibrosis without pneumotoxicity.

PMID- 29190498
TI  - A gapmer aptamer nanobiosensor for real-time monitoring of transcription and
      translation in single cells.
AB  - Transcription and translation are under tight spatiotemporal regulation among
      cells to coordinate multicellular organization. Methods that allow massively
      parallel detection of gene expression dynamics at the single cell level are
      required for elucidating the complex regulatory mechanisms. Here we present a
      multiplex nanobiosensor for real-time monitoring of protein and mRNA expression
      dynamics in live cells based on gapmer aptamers and complementary locked nucleic
      acid probes. Using the multiplex nanobiosensor, we quantified spatiotemporal
      dynamics of vascular endothelial growth factor A mRNA and protein expressions in
      single human endothelial cells during microvascular self-organization. Our
      results revealed distinct gene regulatory processes in the heterogeneous cell
      subpopulations.

PMID- 29190499
TI  - Crosstalk between developing vasculature and optogenetically engineered skeletal
      muscle improves muscle contraction and angiogenesis.
AB  - Capillary networks surrounding skeletal muscle play an important role in not only
      supplying oxygen and nutrients but also in regulating the myogenesis and repair
      of skeletal muscle tissues. Herein, we model the early stages of 3D vascularized
      muscle fiber formation in vitro using a sequential molding technique to
      investigate interactions between angiogenesis of endothelial cells and myogenesis
      of skeletal muscle cells. Channelrhodopsin-2 C2C12 muscle fiber bundles and 3D
      vascular structures (600 MUm diameter) were formed at 500 MUm intervals in a
      collagen gel. Endothelial cells exhibited an emergent angiogenic sprouting
      behavior over several days, which was modulated by the muscle fiber bundle
      through the secretion of angiopoietin-1. Through a reciprocal response,
      myogenesis was also upregulated by interactions with the vascular cells,
      improving muscle contraction via angiopoetin-1/neuregulin-1 signaling. Moreover,
      continuous training of muscle tissue by optical stimulation induced significantly
      more angiogenic sprouting. This in vitro model could be used to better understand
      the formation of vascularized muscle tissues and to test the interactions between
      muscle growth, repair or training and angiogenesis for applications in tissue
      engineering and regenerative medicine.

PMID- 29190500
TI  - Inhibition of intrinsic coagulation improves safety and tumor-targeted drug
      delivery of cationic solid lipid nanoparticles.
AB  - Cationic solid lipid nanoparticles (cSLNs) are promising nanoparticles for
      controlled drug delivery. Increasing surface charge and/or reducing PEG density
      enhance cellular uptake of cSLNs in vitro, but for unknown reasons fail to
      improve drug delivery in vivo. Herein, we show that cSLNs present a risk for
      systemic platelet activation and aggregation in vivo, and this toxic effect can
      be significantly augmented by increasing the surface charge and reducing the PEG
      density. Furthermore, thrombotic toxicity significantly reduces blood circulation
      time and in vivo cellular uptake of cSLNs. Mechanistic studies revealed that the
      intrinsic coagulation pathway is responsible for cSLN-induced platelet
      activation. Importantly, pretreatment of the recipient mice with heparin, a
      clinically-approved intrinsic coagulation inhibitor, was highly effective in
      preventing toxicity, prolonging the circulation time of cSLNs, and improving cSLN
      based antitumor drug delivery and therapeutic efficacy in tumor-bearing mice.
      This study offers a useful strategy for improving both the safety and efficacy of
      cSLN-based anticancer therapies.

PMID- 29190501
TI  - Biomaterials-based 3D cell printing for next-generation therapeutics and
      diagnostics.
AB  - Building human tissues via 3D cell printing technology has received particular
      attention due to its process flexibility and versatility. This technology enables
      the recapitulation of unique features of human tissues and the all-in-one
      manufacturing process through the design of smart and advanced biomaterials and
      proper polymerization techniques. For the optimal engineering of tissues, a
      higher-order assembly of physiological components, including cells, biomaterials,
      and biomolecules, should meet the critical requirements for tissue morphogenesis
      and vascularization. The convergence of 3D cell printing with a microfluidic
      approach has led to a significant leap in the vascularization of engineering
      tissues. In addition, recent cutting-edge technology in stem cells and genetic
      engineering can potentially be adapted to the 3D tissue fabrication technique,
      and it has great potential to shift the paradigm of disease modeling and the
      study of unknown disease mechanisms required for precision medicine. This review
      gives an overview of recent developments in 3D cell printing and bioinks and
      provides technical requirements for engineering human tissues. Finally, we
      propose suggestions on the development of next-generation therapeutics and
      diagnostics.

PMID- 29190502
TI  - NaCl - Changes stem morphology, anatomy and phloem structure in Lucerne (Medicago
      sativa cv. Gabes): Comparison of upper and lower internodes.
AB  - In M. sativa cv. Gabes plants treated with 150mM NaCl, the height of the stem is
      decreased and the internode number, length and diameter are reduced. This
      depressive effect on growth, but also on photosynthetic activity and water
      balance, is accompanied by structural changes. In the upper internodes, NaCl
      treatment increases cambium development, so that the vascular ring is initiated
      earlier than in controls. In the lower internodes, the number of lignified phloem
      fibers is increased by NaCl, and their wall thickness is augmented, compared to
      controls; in the phloem complex, the nacreous layer is enlarged, the number of
      internal wall ingrowths is increased, but companion cells are damaged. In the
      treated lower internodes, few vessels occur in the secondary xylem, which is by
      contrast rich in lignified fibers and in wide vessels grouped in the metaxylem
      area; protoxylem parenchyma and adjacent pith are also lignified. In addition, in
      treated lower internodes, starch grains are less abundant than in controls, and
      this variation might be related to the decrease of photosynthesis. When taken
      together, qualitative and quantitative results indicate that the saline stress
      has a marked morpho-anatomical impact on the M. sativa Gabes stem. In particular,
      variations of secondary derivative distribution, increased wall thickening,
      lignification of phloem and xylem fibers and damage in the phloem complex are
      NaCl-induced responses, and are more expressed in the lower than in the upper
      internodes. The reinforcement of the stem lignified vasculature is thus a
      positive response to stress, but it has a negative impact on the quality of the
      forage.

PMID- 29190503
TI  - The interaction between human blood neutrophil granulocytes and quantum dots.
AB  - For biomedical applications, it is important to know, which kinds of blood cells
      can capture quantum dots (QDs). The maximum accumulation of QDs was found for the
      monocyte fraction of leukocytes, the minimum binding of QDs was observed for
      lymphocytes. It was found that CdSe/ZnS-MPA QDs are actively absorbed by the
      cells and have more expressed toxicity. The classical mechanism of the
      phagocytosis of QDs was revealed for neutrophils, when the QDs are located in
      phagolysosomes. The capture of QDs by neutrophil granulocytes has resulted in a
      destruction of certain types of QDs. The interaction of the neutrophils with the
      QDs has resulted in the death of the cells by one of the following cell death
      mechanisms: necrosis, apoptosis, autophagy, NETos, or mummification. The
      aggregation of the QDs manifested as an increase of the hydrodynamic diameter of
      the QDs was found to occur under the influence of serum and under the influence
      of blood cells (lymphocytes and neutrophils) in a serum-free medium.

PMID- 29190504
TI  - Phytohormone priming elevates the accumulation of defense-related gene
      transcripts and enhances bacterial blight disease resistance in cassava.
AB  - Cassava bacterial blight (CBB) disease caused by Xanthomonas axonopodis pv.
      manihotis (Xam) is a severe disease in cassava worldwide. In addition to causing
      significant cassava yield loss, CBB disease has not been extensively studied,
      especially in terms of CBB resistance genes. The present research demonstrated
      the molecular mechanisms underlining the defense response during Xam infection in
      two cassava cultivars exhibiting different degrees of disease resistance, Huay
      Bong60 (HB60) and Hanatee (HN). Based on gene expression analysis, ten of twelve
      putative defense-related genes including, leucine-rich repeat receptor-like
      kinases (LRR-RLKs), resistance (R), WRKY and pathogenesis-related (PR) genes,
      were differentially expressed between these two cassava cultivars during Xam
      infection. The up-regulation of defense-related genes observed in HB60 may be the
      mechanism required for the reduction of disease severity in the resistant
      cultivar. Interestingly, priming with salicylic acid (SA) or methyl jasmonate
      (MeJA) for 24 h before Xam inoculation could enhance the defense response in both
      cassava cultivars. The disease severity was decreased 10% in the resistant
      cultivar (HB60) and was remarkably reduced 21% in the susceptible cultivar (HN)
      by SA/MeJA priming. Priming with Xam inoculation modulated cassava4.1_013417,
      cassava4.1_030866 and cassava4.1_020555 (highest similarity to MeWRKY59, MePR1
      and AtPDF2.2, respectively) expression and led to enhanced resistance of the
      susceptible cultivar in the second infection. The putative cis-regulatory
      elements were predicted in an upstream region of these three defense-related
      genes. The different gene expression levels in these genes between the two
      cultivars were due to the differences in cis-regulatory elements in their
      promoter regions. Taken together, our study strongly suggested that the induction
      of defense-related genes correlated with defense resistance against Xam
      infection, and exogenous application of SA or MeJA could elevate the defense
      response in both cultivars of cassava. This finding should pave the way for
      management to reduce yield loss from disease and genetic improvement in cassava.

PMID- 29190511
TI  - Follow (or don't follow) the crowd: Young children's conformity is influenced by
      norm domain and age.
AB  - This study investigated whether young children's conformity to a consensus varies
      across the normative domain and age. A total of 168 3- and 5-year-olds
      participated. Each child was presented with a puzzle box that had two transparent
      compartments. In a reward preference condition, one of the compartments contained
      1 sticker, whereas the other compartment contained 12 stickers. In perceptual
      judgment and arbitrary preference conditions, one compartment contained a short
      plank, whereas one contained a perceptually longer plank. Each child was shown a
      video of four female adults, each of whom was asked the same question within
      condition: "Which one's the biggest?" (perceptual task; each model retrieved the
      smaller block), "Which one do you want?" (reward preference; each model retrieved
      the smaller reward), and "Which one do you want?" (arbitrary preference; each
      model retrieved the smaller plank). Children were then asked the same question by
      condition and were allowed to retrieve the item. Notably, more children conformed
      in the arbitrary preference condition than in the reward preference and
      perceptual judgment conditions, with 3-year-olds conforming significantly more
      than 5-year-olds. The 5-year-olds were more successful and imitated with greater
      fidelity, including demonstrating overimitation. However, less overimitation was
      observed in the arbitrary preference condition. Together, these findings show
      that children are sensitive to the contextual cues of the domain in which they
      are witnessing norms and vary their own conformity based on such cues.
      Furthermore, children can navigate which information to copy to fulfil their own
      ends.

PMID- 29190516
TI  - 57Fe internal field nuclear magnetic resonance and Mossbauer spectroscopy study
      of Li-Zn ferrites.
AB  - We report the internal field nuclear magnetic resonance (IFNMR) and Mossbauer
      spectroscopy study of Li-Zn ferrites at RT. The results were supported by the
      IFNMR data measured at 77 K. As Zn concentration increases the IFNMR echo
      amplitude decreases and below certain Zn concentration no signal was detected. At
      RT the echo amplitude vanishes at a lower Zn concentration, whereas at 77 K, the
      echo amplitude does not vanish completely (except for pure Zn-ferrite). However,
      in Mossbauer spectroscopy at RT, we have observed magnetically ordered state of
      all the Li-Zn ferrite samples. This discrepancy could be related to the
      difference between the time scale of detection of the spins by Mossbauer
      spectroscopy (10-7-10-10 s) and NMR spectroscopy (10-6 s). Hence, sensitivity of
      zero-field NMR depends on the magnetic hyperfine field, temperature and abundance
      of the magnetic cations at the lattice of the spinel ferrites. We have
      demonstrated that the 'two-equal-pulses' sequence leads to higher echo signal
      than the spin echo pulse sequence due to the presence of distribution of internal
      magnetic fields throughout the material. We obtained a limiting value for the
      fraction of spins needed to produce an echo signal at a particular temperature
      and at a particular site of the Li-Zn ferrite spinels that can be sensitively
      detected by pulsed IFNMR technique.

PMID- 29190505
TI  - Advances in sarcoma gene mutations and therapeutic targets.
AB  - Sarcomas are rare and complex malignancies that have been associated with a poor
      prognostic outcome. Over the last few decades, traditional treatment with surgery
      and/or chemotherapy has not significantly improved outcomes for most types of
      sarcomas. In recent years, there have been significant advances in the
      understanding of specific gene mutations that are important in driving the
      pathogenesis and progression of sarcomas. Identification of these new gene
      mutations, using next-generation sequencing and advanced molecular techniques,
      has revealed a range of potential therapeutic targets. This, in turn, may lead to
      the development of novel agents targeted to different sarcoma subtypes. In this
      review, we highlight the advances made in identifying sarcoma gene mutations,
      including those of p53, RB, PI3K and IDH genes, as well as novel therapeutic
      strategies aimed at utilizing these mutant genes. In addition, we discuss a
      number of preclinical studies and ongoing early clinical trials in sarcoma
      targeting therapies, as well as gene editing technology, which may provide a
      better choice for sarcoma patient management.

PMID- 29190508
TI  - Evaluation of sediment and 137Cs redistribution in the Oginosawa River catchment
      near the Fukushima Dai-ichi Nuclear Power Plant using integrated watershed
      modeling.
AB  - The Oginosawa River catchment lies 15 km south-west of the Fukushima Dai-ichi
      nuclear plant and covers 7.7 km2. Parts of the catchment were decontaminated
      between fall 2012 and March 2014 in preparation for the return of the evacuated
      population. The General-purpose Terrestrial Fluid-flow Simulator (GETFLOWS) code
      was used to study sediment and 137Cs redistribution within the catchment,
      including the effect of decontamination on redistribution. Fine resolution grid
      cells were used to model local features of the catchment, such as paddy fields
      adjacent to the Oginosawa River. The simulation was verified using monitoring
      data for river water discharge rates (r = 0.92), suspended sediment
      concentrations, and particulate 137Cs concentrations (r = 0.40). Cesium-137 input
      to watercourses came predominantly from land adjacent to river channels and
      forest gullies, e.g. the paddy fields in the Ogi and Kainosaka districts, as the
      ground in these areas saturates during heavy rain and is easily eroded. A
      discrepancy between the simulation and monitoring results on the sediment
      discharge rate following decontamination may be explained by fast erosion
      occurring after decontamination. Forested areas far from the channels only made a
      minor contribution to 137Cs input to watercourses, total erosion of between 0.001
      and 0.1 mm from May 2011 to December 2015, as ground saturation is infrequent in
      these areas. The 2.3-6.9% y-1 decrease in the amount of 137Cs in forest topsoil
      over the study period can be explained by radioactive decay (approximately 2.3% y
      1), along with a migration downwards into subsoil and a small amount of export.
      The amount of 137Cs available for release from land adjacent to rivers is
      expected to be lower in future than compared to this study period, as the
      simulations indicate a high depletion of inventory from these areas by the end of
      2015. However continued monitoring of 137Cs concentrations in river water over
      future years is advised, as recultivation of paddy fields by returnees may again
      lead to fast erosion rates and release of the remaining inventory.

PMID- 29190518
TI  - Multiple focal nodular hyperplasia: MRI features.
AB  - PURPOSE: To describe MRI features of multiple Focal Nodular Hyperplasia (FNHs).
      METHODS: 40 consecutive subjects (37 females, mean age, 38.8years) were included.
      All studies were independently reviewed. This was an observational study to
      define the radiological features of multifocal FNH. RESULTS: 130 lesions were
      evaluated. The majority (88.5%), were peripheral in location. 92.3% lesions were
      lobulated. Marked enhancement was present in 94.6% lesions. In the portal venous
      and delayed phase, 46.2% and 47.7% lesions were mildly hyperintense. Central scar
      was present in 77% lesions. CONCLUSIONS: Distinctive features included
      predominant subcapsular location and mild hyperintensity in the delayed phase,
      seen in nearly 50% of FNHs.

PMID- 29190515
TI  - B1 gradient coherence selection using a tapered stripline.
AB  - Pulsed-field gradients are common in modern liquid state NMR pulse sequences.
      They are often used instead of phase cycles for the selection of coherence
      pathways, thereby decreasing the time required for the NMR experiment. Soft off
      resonance pulses with a B1 gradient result in a spatial encoding similar to that
      created by pulsed-field (B0) gradients. In this manuscript we show that pulse
      sequences with pulsed-field gradients can easily be converted to one which uses
      off-resonance B1 field gradient (OFFBEAT) pulses. The advantage of B1 gradient
      pulses for coherence selection is that the chemical shift evolution during the
      pulses is (partially) suppressed. Therefore no refocusing echos are required to
      correct for evolution during the gradient pulses. A tapered stripline is shown to
      be a convenient tool for creating a well-defined gradient in the B1 field
      strength. B1 gradient coherence selection using a tapered stripline is a simple
      and cheap alternative to B0 pulsed-field gradients.

PMID- 29190510
TI  - Predicted activity of UGT2B7, ABCB1, OPRM1, and COMT using full-gene haplotypes
      and their association with the CYP2D6-inferred metabolizer phenotype.
AB  - The pharmacogene, CYP2D6, is commonly used to infer metabolizer phenotype of many
      marketed drugs and endogenous toxins in ante- and post-mortem patients but only
      represents the efficiency of phase 1 metabolism. Downstream metabolic enzymes
      encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable
      individual response to drugs due to their activity at different stages of the
      tramadol ADME (absorption, distribution, metabolism, and excretion) process.
      While commonly studied as single genes using targeted genotyping approaches, a
      more comprehensive tramadol metabolism profile has not been evaluated. 1000
      Genomes Project data for UGT2B7, ABCB1, OPRM1, and COMT were used to characterize
      full-gene haplotypes and their effect on protein function using in-house excel
      based workbooks, PopART, and TreeView. Population genetic summary statistics and
      intergenic analyses associated these haplotypes with full-gene CYP2D6-inferred
      metabolizer phenotype. The findings suggest that UGT2B7, ABCB1, OPRM1, and COMT
      may contribute to predicted metabolizer phenotype as opposed to relying solely on
      CYP2D6.

PMID- 29190513
TI  - The role of algal organic matter in the separation of algae and cyanobacteria
      using the novel "Posi" - Dissolved air flotation process.
AB  - Algae and cyanobacteria frequently require separation from liquid media in both
      water treatment and algae culturing for biotechnology applications. The
      effectiveness of cell separation using a novel dissolved air flotation process
      that incorporates positively charged bubbles (PosiDAF) has recently been of
      interest but has been shown to be dependent on the algae or cyanobacteria species
      tested. Previously, it was hypothesised that algal organic matter (AOM) could be
      impacting the separation efficiency. Hence, this study investigates the influence
      of AOM on cell separation using PosiDAF, in which bubbles are modified using a
      commercially available cationic polyelectrolyte poly(N, N-diallyl-N,N
      dimethylammonium chloride) (PDADMAC). The separation of Chlorella vulgaris CS
      42/7, Mychonastes homosphaera CS-556/01 and two strains of Microcystis aeruginosa
      (CS-564/01 and CS-555/1), all of which have similar cell morphology but different
      AOM character, was investigated. By testing the cell separation in the presence
      and absence of AOM, it was determined that AOM enhanced cell separation for all
      the strains but to different extents depending on the quantity and composition of
      carbohydrates and proteins in the AOM. By extracting AOM from the strain for
      which optimal separation was observed and adding it to the others, cell
      separation improved from <55% to >90%. This was attributed to elevated levels of
      acidic carbohydrates as well as glycoprotein-carbohydrate conjugations, which in
      turn were related to the nature and quantity of proteins and carbohydrates
      present in the AOM. Therefore, it was concluded that process optimisation
      requires an in-depth understanding of the AOM and its components. If culturing
      algae for biotechnology applications, this indicates that strain selection is not
      only important with respect to high value product content, but also for cell
      separation.

PMID- 29190520
TI  - Calibration matters: On the procedure of using the chlorophyll fluorescence
      method to estimate mesophyll conductance.
AB  - Estimates of mesophyll conductance (gm), when calculated from chlorophyll
      fluorescence, are uncertain, especially when the photosystem II (PSII) operating
      efficiency is measured from the traditional single saturation pulse methodology.
      The multiphase flash method has recently been recommended to replace the single
      saturation pulse method, allowing a more reliable estimation of gm. Also, many
      researchers still directly use the PSII operating efficiency to derive linear
      electron transport rate J (that is required to estimate gm), without appropriate
      calibration using measurements under non-photorespiratory conditions. Here we
      demonstrate for tomato and rice that (i) using the multiphase flash method did
      not yield realistic estimates of gm if no calibration was conducted; and (ii)
      using the single saturation pulse method still gave reasonable estimates of gm
      when calibration based on the non-photorespiratory measurements was properly
      conducted. Therefore, conducting calibration based on data under non
      photorespiratory conditions was indispensable for a reliable estimation of gm,
      regardless whether the multiphase flash or the single saturation pulse method was
      used for measuring the PSII operating efficiency. Other issues related to the
      procedure of using the chlorophyll fluorescence method to estimate gm were
      discussed.

PMID- 29190519
TI  - The predictive value of computed tomography in the detection of reflux
      esophagitis in patients undergoing upper endoscopy.
AB  - BACKGROUND: Reflux esophagitis (RE) may mimic symptoms requiring cross-sectional
      imaging. METHODS: From 565 patients who had CT and esophagogastroduodenoscopy
      within four days apart, CT scans of 72 patients with RE confirmed by
      esophagogastroduodenoscopy and 108 matched patients without RE were evaluated for
      distal esophageal wall characteristics. RESULTS: In RE patients the distal
      esophageal wall thickness was greater (5.2+/-2.0mm) compared to patients without
      RE (3.5+/-1.2mm, p<0.0001) with AUC of 0.78 and 56% sensitivity, 88% specificity
      for a 5.0mm cut-off. CONCLUSIONS: There is a moderate association between distal
      esophageal wall thickness on CT and RE diagnosed by esophagogastroduodenoscopy as
      the reference standard.

PMID- 29190512
TI  - Free nitrous acid pre-treatment of waste activated sludge enhances volatile
      solids destruction and improves sludge dewaterability in continuous anaerobic
      digestion.
AB  - Previous work has demonstrated that pre-treatment of waste activated sludge (WAS)
      with free nitrous acid (FNA i.e. HNO2) enhances the biodegradability of WAS,
      identified by a 20-50% increase in specific methane production in biochemical
      methane potential (BMP) tests. This suggests that FNA pre-treatment would enhance
      the destruction of volatile solids (VS) in an anaerobic sludge digester, and
      reduce overall sludge disposal costs, provided that the dewaterability of the
      digested sludge is not negatively affected. This study experimentally evaluates
      the impact of FNA pre-treatment on the VS destruction in anaerobic sludge
      digestion and on the dewaterability of digested sludge, using continuously
      operated bench-scale anaerobic digesters. Pre-treatment of full-scale WAS for 24
      h at an FNA concentration of 1.8 mg NN/L enhanced VS destruction by 17 +/- 1%
      (from 29.2 +/- 0.9% to 34.2 +/- 1.1%) and increased dewaterability (centrifuge
      test) from 12.4 +/- 0.4% to 14.1 +/- 0.4%. Supporting the VS destruction data,
      methane production increased by 16 +/- 1%. Biochemical methane potential tests
      indicated that the final digestate stability was also improved with a lower
      potential from FNA treated digestate. Further, a 2.1 +/- 0.2 log improvement in
      pathogen reduction was also achieved. With inorganic solids representing 15-22%
      of the full-scale WAS used, FNA pre-treatment resulted in a 16-17% reduction in
      the volume of dewatered sludge for final disposal. This results in significantly
      reduced costs as assessed by economic analysis.

PMID- 29190507
TI  - Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma
      patients included in the French OS2006/sarcome-09 study.
AB  - BACKGROUND: In most countries, reference chemotherapy for osteosarcoma is MAP
      regimen (M = high-dose methotrexate, AP = doxorubicin-cisplatinum). In France,
      the standard preoperative chemotherapy for children/adolescents combines M and
      etoposide-ifosfamide (EI), based on the OS94-trial. We report the safety and
      efficacy results of patients <=25 years treated with preoperative M-EI regimen
      enroled in the French OS2006-study, between 2007 and 2014. METHODS: Treatment
      comprised preoperative chemotherapy with the 7 M-courses and 2 EI-courses, then
      surgery and postoperative chemotherapy assigned by risk's groups: standard-risk
      (good histological response without metastases) received 12 M-courses, 3 EI
      courses; high-risk (poor histologic response, initial metastases or unresectable
      primary) received 5 M-courses alternated with 5 AP-courses. 253 patients were
      randomised to receive (n = 128) or not (n = 125) zoledronate. RESULTS: 409/522
      patients enroled in the OS2006 study who received preoperative M-EI were
      analysed. Median age was 14.3 years (4.7-24.5), with 55 patients aged 18-25
      years. Primary tumour location was limb in 383 patients (94%) and 85 (21%)
      presented metastases. Median chemotherapy duration was 37.4 weeks. 381 (96%)
      patients underwent surgery, 258 patients (65%) had a good histologic response.
      187/324 patients (58%) with localised disease did not receive doxorubicin nor
      cisplatinum. Toxicity was evaluated in the randomised study: most patients
      experienced >=1 severe toxicity (grade IV haematological or grade III/IV extra
      haematological). Median follow-up was 4.8 years, and 168 patients had events.
      Five-year event-free survival was 56% (95% CI, 51-62%) and overall survival 71%
      (66-76%). CONCLUSION: M-EI regimen/strategy was feasible for patient aged <=25
      years with survival rates are comparable to those obtained with MAP regimen.

PMID- 29190506
TI  - Mammographic density and breast cancer risk in breast screening assessment cases
      and women with a family history of breast cancer.
AB  - BACKGROUND: Mammographic density has been shown to be a strong independent
      predictor of breast cancer and a causative factor in reducing the sensitivity of
      mammography. There remain questions as to the use of mammographic density
      information in the context of screening and risk management, and of the
      association with cancer in populations known to be at increased risk of breast
      cancer. AIM: To assess the association of breast density with presence of cancer
      by measuring mammographic density visually as a percentage, and with two
      automated volumetric methods, QuantraTM and VolparaDensityTM. METHODS: The
      TOMosynthesis with digital MammographY (TOMMY) study of digital breast
      tomosynthesis in the Breast Screening Programme of the National Health Service
      (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases
      (of whom 1158 had breast cancer) and 1040 screened women with a family history of
      breast cancer (of whom two had breast cancer). We assessed the association of
      each measure with breast cancer risk in these populations at enhanced risk, using
      logistic regression adjusted for age and total breast volume as a surrogate for
      body mass index (BMI). RESULTS: All density measures showed a positive
      association with presence of cancer and all declined with age. The strongest
      effect was seen with Volpara absolute density, with a significant 3% (95% CI 1
      5%) increase in risk per 10 cm3 of dense tissue. The effect of Volpara volumetric
      density on risk was stronger for large and grade 3 tumours. CONCLUSIONS:
      Automated absolute breast density is a predictor of breast cancer risk in
      populations at enhanced risk due to either positive mammographic findings or
      family history. In the screening context, density could be a trigger for more
      intensive imaging.

PMID- 29190522
TI  - Ultrasound and MRI of nerves for monitoring disease activity and treatment
      effects in chronic dysimmune neuropathies - Current concepts and future
      directions.
AB  - New imaging modalities like high-resolution-ultrasound (HRUS) and MR-Neurography
      (MRN) are increasingly used for the evaluation of the peripheral nervous system.
      The increasing knowledge on morphological changes observed in different
      neuropathies has led to a better understanding of underlying pathophysiological
      processes. The diagnosis of acquired chronic dysimmune neuropathies (CDN) like
      chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis-Sumner Syndrome
      (LSS) or multifocal motor neuropathy (MMN) can be challenging. The current
      diagnostic criteria and outcome parameters are mainly based on clinical and
      electrophysiological parameters. Especially in CDN cases with atypical
      presentation or during early disease stages, the diagnostic accuracy is low and
      standardized protocols for the evaluation of disease activity and treatment
      response are lacking. The establishment of combined diagnostic criteria for CDN
      including imaging modalities could help to improve the diagnostic accuracy, allow
      a better differentiation of subtypes and facilitate the follow-up of disease
      course. The appropriate selection of eligible patients and sensitive monitoring
      of treatment response is mandatory future in treatment trials. In this article,
      we briefly summarize the clinical presentations and pathophysiological concepts
      of different CDN like CIDP, LSS and MMN. Furthermore, this review focuses on the
      diagnostic value of HRUS/MRN and its potential role for the monitoring of disease
      activity.

PMID- 29190517
TI  - Comparing residence-based to actual path-based methods for defining adolescents'
      environmental exposures using granular spatial data.
AB  - This paper uses data from a population-based case control study of daily
      activities and assault injury to examine residence-based versus actual path-based
      approaches to measuring environmental exposures that pose risks for violence
      among adolescents. Defining environmental exposures based on participant home
      address resulted in significant misclassification compared to gold standard daily
      travel path measures. Dividing participant daily travel paths into origin
      destination segments, we explore a method for defining spatial counterfactuals by
      comparing actual trip path exposures to shortest potential trip path exposures.
      Spatial methods explored herein can be utilized in future research to more
      accurately quantify environmental exposures and associations with health
      outcomes.

PMID- 29190526
TI  - The influence of perceptual similarity and individual differences on false
      memories in aging.
AB  - Previous false memory research has suggested that older adults' false memories
      are based on an overreliance on gist processing in the absence of item-specific
      details. Yet, false memory studies have rarely taken into consideration the
      precise role of item-item similarity on the cognitive and neural mechanisms
      underlying perceptual false memories in older adults. In addition, work in our
      laboratory has suggested that when investigating the neural basis of false
      memories in older adults, it is equally as critical to take into account
      interindividual variability in behavior. With both factors in mind, the present
      study was the first to examine how both controlled, systematic differences in
      perceptual relatedness between targets and lures and individual differences in
      true and false recognition contribute to the neural basis of both true and false
      memories in older adults. Results suggest that between-subject variability in
      memory performance modulates neural activity in key regions associated with false
      memories in aging, whereas systematic differences in perceptual similarity did
      not modulate neural activity associated with false memories.

PMID- 29190525
TI  - Cognitive reserve modulates attention processes in healthy elderly and amnestic
      mild cognitive impairment: An event-related potential study.
AB  - OBJECTIVES: The study aimed to investigate and compare the effect of cognitive
      reserve (CR) on brain activation in healthy controls (HC) and amnestic mild
      cognitive impairment (aMCI) patients during 0-back and 1-back tasks measured by
      event-related potential (ERP). METHODS: The study recorded 85 subjects (39 aMCI
      patients and 46 their matched controls) with a 64-channel electroencephalogram
      (EEG). Subjects performed 0- and 1-back tasks. RESULTS: Compared to HC, aMCI
      patients showed reduced accuracy, delayed mean correct response time (RT) and
      decreased P300 amplitude at central-parietal and parietal electrodes. A mediation
      analysis indicated that higher CR reduced neural inefficiency, which might be
      associated with better task performance in HC. However, no correlation was
      detected between CR and neural inefficiency in aMCI patients, whereas higher CR
      was still related to enhanced accuracy and prolonged RT in aMCI patients.
      CONCLUSIONS: The present study reported that higher CR could contribute to better
      task performance via down-regulating neural inefficiency in HC. In addition,
      higher CR might modulate attention processes in aMCI via a way distinct from that
      in HC, and eventually result in better task performance. SIGNIFICANCE: The study
      provided evidence for that improving CR might lower cognitive impairment of
      healthy elderly and aMCI patients.

PMID- 29190509
TI  - Genetic determinants of freckle occurrence in the Spanish population: Towards
      ephelides prediction from human DNA samples.
AB  - Prediction of human pigmentation traits, one of the most differentiable
      externally visible characteristics among individuals, from biological samples
      represents a useful tool in the field of forensic DNA phenotyping. In spite of
      freckling being a relatively common pigmentation characteristic in Europeans,
      little is known about the genetic basis of this largely genetically determined
      phenotype in southern European populations. In this work, we explored the
      predictive capacity of eight freckle and sunlight sensitivity-related genes in
      458 individuals (266 non-freckled controls and 192 freckled cases) from Spain.
      Four loci were associated with freckling (MC1R, IRF4, ASIP and BNC2), and female
      sex was also found to be a predictive factor for having a freckling phenotype in
      our population. After identifying the most informative genetic variants
      responsible for human ephelides occurrence in our sample set, we developed a DNA
      based freckle prediction model using a multivariate regression approach. Once
      developed, the capabilities of the prediction model were tested by a repeated 10
      fold cross-validation approach. The proportion of correctly predicted individuals
      using the DNA-based freckle prediction model was 74.13%. The implementation of
      sex into the DNA-based freckle prediction model slightly improved the overall
      prediction accuracy by 2.19% (76.32%). Further evaluation of the newly-generated
      prediction model was performed by assessing the model's performance in a new
      cohort of 212 Spanish individuals, reaching a classification success rate of
      74.61%. Validation of this prediction model may be carried out in larger
      populations, including samples from different European populations. Further
      research to validate and improve this newly-generated freckle prediction model
      will be needed before its forensic application. Together with DNA tests already
      validated for eye and hair colour prediction, this freckle prediction model may
      lead to a substantially more detailed physical description of unknown individuals
      from DNA found at the crime scene.

PMID- 29190514
TI  - Extracellular vesicles in leukemia.
AB  - Extracellular vesicles (EV) are nano-sized membrane enclosed vehicles that are
      involved in cell-to-cell communication and carry cargo that is representative of
      the parent cell. Recent studies have highlighted the significant roles leukemia
      EVs play in tumor progression, and ways in which they can lead to treatment
      evasion, thus meriting further investigation. Leukemia EVs are involved in
      crosstalk between the leukemia cell and its surroundings, transforming it into a
      cancer favorable microenvironment. Due to the diverse biological content found in
      leukemia EVs, they have an assortment of effects on the cells they interact with
      and can be harnessed as candidates for diagnostic and therapeutic treatments.
      This review focuses on EVs in the context of leukemia and the means by which they
      modulate their microenvironment, hematopoiesis, and the immune system to
      facilitate malignancy. We will also address current and prospective EV-based
      therapeutics.

PMID- 29190521
TI  - Presurgical language mapping using event-related high-gamma activity: The Detroit
      procedure.
AB  - A number of investigators have reported that event-related augmentation of high
      gamma activity at 70-110 Hz on electrocorticography (ECoG) can localize
      functionally-important brain regions in children and adults who undergo epilepsy
      surgery. The advantages of ECoG-based language mapping over the gold-standard
      stimulation include: (i) lack of stimulation-induced seizures, (ii) better
      sensitivity of localization of language areas in young children, and (iii)
      shorter patient participant time. Despite its potential utility, ECoG-based
      language mapping is far less commonly practiced than stimulation mapping. Here,
      we have provided video presentations to explain, point-by-point, our own hardware
      setting and time-frequency analysis procedures. We also have provided
      standardized auditory stimuli, in multiple languages, ready to be used for ECoG
      based language mapping. Finally, we discussed the technical aspects of ECoG-based
      mapping, including its pitfalls, to facilitate appropriate interpretation of the
      data.

PMID- 29190527
TI  - Urinary polycyclic aromatic hydrocarbon metabolites, Club cell secretory protein
      and lung function.
AB  - BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been
      associated with lung function decline. However, the underlying mechanisms for the
      association remain unclear. OBJECTIVES: To explore potential role of a lung
      epithelial biomarker, Club cell secretory protein (CC16), in associations between
      PAH exposures and lung function decline. METHODS: We investigated 3384 adults
      from the Wuhan-Zhuhai cohort, and followed up at three years after first
      examination. Linear mixed models was used to quantify dose-response relationships
      between urinary monohydroxylated PAH metabolites (OH-PAHs) and lung function, as
      well as OH-PAHs and plasma CC16. Mediation analysis was conducted to investigate
      role of CC16 in the association between OH-PAHs and lung function. We also
      estimated the relationships between OH-PAHs and lung function change in three
      years among participants with different levels of CC16. RESULTS: Each 1-unit
      increase of log-transformed total urinary high and low molecular weight OH-PAHs
      (?HMW OH-PAH and ?LMW OH-PAHs) were associated with a 22.59 and 25.25ml reduction
      of FEV1 respectively, while?HMW OH-PAH was associated with a 30.38ml reduction of
      FVC. Moreover, these negative associations between OH-PAHs and lung function
      levels were significant only among low CC16 group (<15.83ng/ml). CC16
      concentration decreased monotonically with increased high molecular weight OH
      PAHs (?HMW OH-PAHs) when ?HMW OH-PAH concentration was over 0.67MUg/mmol Cr. CC16
      mediated 22.13% of the association between ?HMW OH-PAH and FVC among individuals
      with higher ?HMW OH-PAH. After three years of follow-up, subjects with low level
      of plasma CC16 had a significant decline of FVC when exposed to high level of
      ?HMW OH-PAH. CONCLUSIONS: CC16 play an important role in the association between
      high molecular weight PAHs and FVC. Individuals with low plasma CC16 level might
      suffer a decline in lung function when exposed to high level of high molecular
      weight PAHs.

PMID- 29190523
TI  - Electromagnetic source imaging using simultaneous scalp EEG and intracranial EEG:
      An emerging tool for interacting with pathological brain networks.
AB  - OBJECTIVE: The goal of this study is to investigate the performance, merits and
      limitations of source imaging using intracranial EEG (iEEG) recordings and to
      compare its accuracy to the results of EEG source imaging. Accuracy in this
      study, is measured both by determining the location and inter-nodal connectivity
      of underlying brain networks. METHODS: Systematic computer simulation studies are
      conducted to evaluate iEEG-based source imaging vs. EEG-based source imaging, and
      source imaging using both EEG and iEEG. To test the source imaging models,
      networks of inter-connected nodes (in terms of activity) are simulated. The
      location of the network nodes is randomly selected within a realistic geometry
      head model and a connectivity link is created among these nodes based on a multi
      variate auto-regressive (MVAR) model. Then the forward problem is solved to
      calculate the potentials at the electrodes and noise (white and correlated) is
      added to these simulated potentials to simulate realistic measurements.
      Subsequently, the inverse problem is solved and an algorithm based on principle
      component analysis is performed on the estimated source activities to determine
      the location of the simulated network nodes. The activity of these nodes (over
      time), is then extracted, and used to estimate the connectivity links among the
      mentioned nodes using Granger causality analysis. RESULTS: Source imaging based
      on iEEG recordings may or may not improve the accuracy in localization, depending
      on the number and location of active nodes relative to iEEG electrodes and to
      other nodes within the network. However, our simulation results suggest that
      combining EEG and iEEG modalities (simultaneous scalp and intracranial
      recordings) can improve the imaging accuracy significantly. CONCLUSIONS: While
      iEEG source imaging is useful in estimating the exact location of sources near
      the iEEG electrodes, combining EEG and iEEG recordings can achieve a more
      accurate imaging due to the high spatial coverage of the scalp electrodes and the
      added near field information provided by the iEEG electrodes. SIGNIFICANCE: The
      present results suggest the feasibility of localizing brain electrical sources
      from iEEG recordings and improving EEG source localization using simultaneous EEG
      and iEEG recordings to cover the whole brain. The hybrid EEG and iEEG source
      imaging can assist the clinicians when unequivocal decisions about determining
      the epileptogenic zone cannot be reached using a single modality.

PMID- 29190524
TI  - Four-dimensional map of the human early visual system.
AB  - OBJECTIVE: We generated a large-scale, four-dimensional map of neuronal
      modulations elicited by full-field flash stimulation. METHODS: We analyzed
      electrocorticography (ECoG) recordings from 63 patients with focal epilepsy, and
      delineated the spatial-temporal dynamics of visually-elicited high-gamma70-110 Hz
      amplitudes on a standard brain template. We then clarified the neuronal events
      underlying visual evoked potential (VEP) components, by correlating with high
      gamma amplitude measures. RESULTS: The medial-occipital cortex initially revealed
      rapid neural activation followed by prolonged suppression, reflected by
      augmentation of high-gamma activity lasting up to 100 ms followed by attenuation
      lasting up to 1000 ms, respectively. With a number of covariate factors
      incorporated into a prediction model, the eccentricity representation
      independently predicted the magnitude of post-activation suppression, which was
      more intense in regions representing more parafoveal visual fields compared to
      those of more peripheral fields. The initial negative component on VEP was
      sharply contoured and co-occurred with early high-gamma augmentation, whose
      offset then co-occurred with a large positive VEP peak. A delayed negative VEP
      peak was blunt and co-occurred with prolonged high-gamma attenuation.
      CONCLUSIONS: Eccentricity-dependent gradient in neural suppression in the medial
      occipital region may explain the functional difference between peripheral and
      parafoveal/central vision. Early negative and positive VEP components may reflect
      neural activation, whereas a delayed negative VEP peak reflecting neural
      suppression. SIGNIFICANCE: Our observation provides the mechanistic rationale for
      transient scotoma or mild flash-blindness, characterized by physiological
      afterimage preferentially formed in central vision following intense but non
      injurious light exposure.

PMID- 29190530
TI  - Rare missense coding variants in oxytocin receptor (OXTR) in schizophrenia cases
      are associated with early trauma exposure, cognition and emotional processing.
AB  - BACKGROUND: Oxytocin is a peptide hormone that influences the integration of
      social cognition with behavior and affect regulation. Oxytocin also prominently
      directs the transition of neuronal GABA neurotransmission from excitatory to
      inhibitory after birth. The oxytocin receptor (OXTR) is linked to schizophrenia,
      a heterogeneous syndrome. Relationships of OXTR polymorphisms with specific
      clinical features could aid in evaluating any role of oxytocin in the
      pathogenesis of schizophrenia. METHOD: Schizophrenia cases with rare missense
      coding OXTR single nucleotide variants (SNVs) were identified from a well
      characterized sample of cases and controls who were assessed for symptoms,
      cognition and early life trauma. RESULTS: Five of 48 cases showed rare OXTR
      variants. Compared to the other cases they had less severe negative symptoms
      (deficits in emotional expression and motivation) and less severe general
      psychopathology scores (depression and anxiety). They demonstrated lower
      nonverbal (performance) than verbal intelligence due to deficient perceptual
      organization and slow processing speed. They also reported greater early trauma
      exposure (physical and sexual abuse and emotional trauma). CONCLUSION: Cases
      carrying rare OXTR SNVs had less negative and affective symptoms than other
      cases, but similar psychotic symptoms, along with specific cognitive deficits.
      The clinical characterization of these cases occurred in association with
      environmental exposure to early trauma, especially sexual abuse, which may have
      influenced the expression of schizophrenia in subjects harboring specific SNVs in
      the OXTR.

PMID- 29190532
TI  - Effect of wetting case and softness on adhesion of bioinspired micropatterned
      surfaces.
AB  - Inspired by the adhesive ability of amphibian toe-pads, polydimethylsiloxane
      (PDMS) hexagonal pillar arrayed surfaces with varying softness are fabricated,
      and their adhesion behaviors in the non-wetting, mostly wetting and totally
      wetting cases are throughly investigated. Experimental results demonstrate that
      under a totally wetting case, i.e. the biological toe-pad-like case, besides the
      long-range capillary force, a short-range interaction caused by close contact
      plays a significant role for adhesion. Compared with unpatterned surface,
      hexagonal pillar patterns can lead to a remarkable improvement in both short- and
      long-range contribution for wet adhesion. Meanwhile, the surface softness
      performs a beneficial character in the short-range contribution for the adhesion
      of micropillars. Considering the fact that the soft microstructure and the almost
      totally wetting case (low surface tension of secretion and high surface energy of
      epidermis) on the pads of nature species, it is reasonable to suggest that these
      evolutions are in favor for wet attachments.

PMID- 29190528
TI  - Daily exceedance concentration hours: A novel indicator to measure acute
      cardiovascular effects of PM2.5 in six Chinese subtropical cities.
AB  - BACKGROUND: Daily mean concentration cannot fully address the hourly variations
      of air pollution within one day. As such, we proposed a new indicator, daily
      exceedance concentration hours (DECH), to explore the acute cardiovascular
      effects of ambient PM2.5 (particles with aerodynamic diameters less than 2.5MUm).
      The DECH in PM2.5 was defined as daily total concentration-hours >25MUg/m3.
      METHODS: A generalized additive model with a quasi-Poisson link was applied to
      estimate the associations between day-to-day variation in PM2.5 DECH and day-to
      day variation in cardiovascular mortality in six subtropical cities in Guangdong
      Province, China. RESULTS: The analysis revealed significant associations between
      PM2.5 DECHs and cardiovascular mortality. A 500MUg/m3*h increase in PM2.5 DECHs
      at lag03 was associated with an increase of 4.55% (95% confidence interval (CI):
      3.59%, 5.52%) in cardiovascular mortality, 4.45% (95% CI: 2.81%, 6.12%) in
      ischemic cardiovascular mortality, 5.02% (95% CI: 3.41%, 6.65%) in
      cerebrovascular mortality, and 3.00% (95% CI: 1.13%, 4.90%) in acute myocardial
      infarction mortality. We further observed a greater mortality burden using PM2.5
      DECHs than daily mean PM2.5 (6478 (95% CI: 5071, 7917) VS 5136 (95% CI: 3990,
      6305)). CONCLUSION: This study reveals that PM2.5 DECH is one important exposure
      indicator of ambient PM2.5 to measure its cardiovascular mortality effects in
      Pearl River Delta region; and that using daily mean concentration could under
      estimate the mortality burden compared with this new indicator.

PMID- 29190533
TI  - Evaluating the critical strain energy release rate of bioactive glass coatings on
      Ti6Al4V substrates after degradation.
AB  - It has been reported that the adhesion of bioactive glass coatings to Ti6Al4V
      reduces after degradation, however, this effect has not been quantified. This
      paper uses bilayer double cantilever (DCB) specimens to determine GIC and GIIC,
      the critical mode I and mode II strain energy release rates, respectively, of
      bioactive coating/Ti6Al4V substrate systems degraded to different extents. Three
      borate-based bioactive glass coatings with increasing amounts of incorporated SrO
      (0, 15 and 25mol%) were enamelled onto Ti6Al4V substrates and then immersed in de
      ionized water for 2, 6 and 24h. The weight loss of each glass composition was
      measured and it was found that the dissolution rate significantly decreased with
      increasing SrO content. The extent of dissolution was consistent with the
      hypothesis that the compressive residual stress tends to reduce the dissolution
      rate of bioactive glasses. After drying, the bilayer DCB specimens were created
      and subjected to nearly mode I and mode II fracture tests. The toughest
      coating/substrate system (one composed of the glass containing 25mol% SrO) lost
      80% and 85% of its GIC and GIIC, respectively, in less than 24h of degradation.
      The drop in GIC and GIIC occurred even more rapidly for other coating/substrate
      systems. Therefore, degradation of borate bioactive glass coatings is inversely
      related to their fracture toughness when coated onto Ti6A4V substrates. Finally,
      roughening the substrate was found to be inconsequential in increasing the
      toughness of the system as the fracture toughness was limited by the cohesive
      toughness of the glass itself.

PMID- 29190529
TI  - A review of emerging adsorbents and current demand for defluoridation of water:
      Bright future in water sustainability.
AB  - Fluoride contamination of groundwater is a serious problem in several countries
      of the world because of the intake of excessive fluoride caused by the drinking
      of the contaminated groundwater. Geological and anthropogenic factors are
      responsible for the contamination of groundwater with fluoride. Excess amounts of
      fluoride in potable water may cause irreversible demineralisation of bone and
      tooth tissues, a condition called fluorosis, and long-term damage to the brain,
      liver, thyroid, and kidney. There has long been a need for fluoride removal from
      potable water to make it safe for human use. From among several defluoridation
      technologies, adsorption is the technology most commonly used due to its cost
      effectiveness, ease of operation, and simple physical process. In this paper, the
      adsorption capacities and fluoride removal efficiencies of different types of
      adsorbents are compiled from relevant published data available in the literature
      and represented graphically. The most promising adsorbents tested so far from
      each category of adsorbents are also highlighted. There is still a need to
      discover the actual feasibility of usage of adsorbents in the field on a
      commercial scale and to define the reusability of adsorbents to reduce cost and
      the waste produced from the adsorption process. The present paper reviews the
      currently available methods and emerging approaches for defluoridation of water.

PMID- 29190534
TI  - Abundance and potential contribution of Gram-negative cheese rind bacteria from
      Austrian artisanal hard cheeses.
AB  - Many different Gram-negative bacteria have been shown to be present on cheese
      rinds. Their contribution to cheese ripening is however, only partially
      understood until now. Here, cheese rind samples were taken from Vorarlberger
      Bergkase (VB), an artisanal hard washed-rind cheese from Austria. Ripening
      cellars of two cheese production facilities in Austria were sampled at the day of
      production and after 14, 30, 90 and 160days of ripening. To obtain insights into
      the possible contribution of Advenella, Psychrobacter, and Psychroflexus to
      cheese ripening, we sequenced and analyzed the genomes of one strain of each
      genus isolated from VB cheese rinds. Additionally, quantitative PCRs (qPCRs) were
      performed to follow the abundance of Advenella, Psychrobacter, and Psychroflexus
      on VB rinds during ripening in both facilities. qPCR results showed that
      Psychrobacter was most abundant on cheese rinds and the abundance of Advenella
      decreased throughout the first month of ripening and increased significantly
      after 30days of ripening (p<0.01). Psychrobacter and Psychroflexus increased
      significantly during the first 30 ripening days (p<0.01), and decreased to their
      initial abundance during the rest of the ripening time (p<0.05). Genome
      sequencing resulted in 17 to 27 contigs with assembly sizes of 2.7 Mbp for
      Psychroflexus, 3 Mbp for Psychrobacter, and 4.3 Mbp for Advenella. Our results
      reveal that each genome harbors enzymes shown to be important for cheese ripening
      in other bacteria such as: Cystathionine/Methionine beta or gamma-lyases, many
      proteases and peptidases (including proline iminopeptidases), aminotransferases,
      and lipases. Thus, all three isolates have the potential to contribute positively
      to cheese ripening. In conclusion, the three species quantified were stable
      community members throughout the ripening process and their abundance on cheese
      rinds together with the results from genome sequencing suggest an important
      contribution of these bacteria to cheese ripening.

PMID- 29190535
TI  - Experiences of nursing undergraduates on a redesigned blended communication
      module: A descriptive qualitative study.
AB  - BACKGROUND: Education is going through accelerated changes to accommodate the
      needs of contemporary students. However, there are ongoing concerns regarding the
      quality of education in communication skills for nurses and other healthcare
      professionals. Many studies have been conducted to evaluate the effectiveness of
      a blended learning pedagogical tool in enhancing the learning of nursing
      undergraduates. However, little is known about students' experiences of a blended
      learning model for teaching communication skills. OBJECTIVE: To explore first
      year nursing students' experiences of the blended learning design adopted in a
      communication module. DESIGN: A descriptive qualitative design was adopted.
      SETTINGS AND PARTICIPANTS: Data were collected in the form of written reflections
      from 74 first year nursing undergraduates who were enrolled in a university
      affiliated nursing school. METHODS: Students were asked to complete an online
      reflective exercise regarding an undergraduate communication module on their last
      day of class, and the submitted reflections were analyzed. A thematic analysis
      was conducted and ethics approval was obtained for this study. RESULTS: Six
      overarching themes and fifteen subthemes were generated. The six overarching
      themes were: 1) Helpful and engaging classroom experience, 2) valuable online
      activities, 3) meaningful assessment, 4) appreciation for interprofessional
      education, 5) personal enrichment, and 6) overall feedback and recommendations.
      CONCLUSIONS: The students in this study felt that the blended pedagogy
      communication module enhanced their learning and boosted their confidence in
      facing similar situations. Interprofessional education was well-accepted among
      students as they attained a deeper understanding on the importance of
      interprofessional learning and an appreciation towards other professionals.
      Blended pedagogy can be used in teaching communication skills to nursing students
      to provide a holistic and up-to-date learning experience. Future studies should
      consider engaging students in face-to-face interviews to obtain a deeper
      understanding on their experiences of a blended pedagogy incorporated
      communication module.

PMID- 29190531
TI  - Effect of two-year degradation on mechanical interaction between a bioresorbable
      scaffold and blood vessel.
AB  - This paper aims to evaluate the mechanical behaviour of a bioresorbable polymeric
      coronary scaffold using finite element method, focusing on scaffold-artery
      interaction during degradation and vessel remodelling. A series of nonlinear
      stress-strain responses was constructed to match the experimental measurement of
      radial stiffness and strength for polymeric scaffolds over 2-year in-vitro
      degradation times. Degradation process was modelled by incorporating the change
      of material property as a function of time. Vessel remodelling was realised by
      changing the size of artery-plaque system manually, according to the clinical
      data in literature. Over degradation times, stress on the scaffold tended to
      increase firstly and then decreased gradually, corresponding to the changing
      yield stress of the scaffold material; whereas the stress on the plaque and
      arterial layers showed a continuous decrease. In addition, stress reduction was
      also observed for scaffold, plaque and artery in the simulations with the
      consideration of vessel remodelling. For the first time, the work offered
      insights into mechanical interaction between a bioresorbable scaffold and blood
      vessel during two-year in-vitro degradation, which has significance in assisting
      with further development of bioresorbable implants for treating cardiovascular
      diseases.

PMID- 29190536
TI  - State-level climate, anti-discrimination law, and sexual minority health status:
      An ecological study.
AB  - How social and legal climate influence LGB health is an under-studied topic. In
      response, this study examines whether the lesbian/gay/bisexual (LGB) climate
      index and presence of anti-discrimination law show population health significance
      for U.S. sexual minorities. The LGB climate index uses survey data collected
      between 2012 and 2013 to gauge states' support of lesbian, gay, and bisexual
      individuals, whereas anti-discrimination law captures any state-level law that
      makes it illegal to discriminate because of sexual orientation in employment,
      housing, and public accommodations. We merge these two contextual measures with
      2011-2015 Behavioral Risk Factor Surveillance System (BRFSS) aggregated,
      individual-level survey data, from which we generate three measures of state
      level rates: excellent self-rated health, routine health care utilization, and
      health insurance among self-identified lesbian/gay and bisexual adults. We find
      that the LGB climate index associates positively with rates of excellent self
      rated health, routine health care utilization, and health insurance-but only for
      states with anti-discrimination laws, and only among lesbian/gay adults. Analyses
      confirm salubrious synergism between a sexually-minority-friendly climate and
      anti-discrimination law-together these two contextual measures interact to
      protect lesbian/gay population health.

PMID- 29190537
TI  - Private or public hospital ownership: Does it really matter?
AB  - Incentives to improve hospital performance under prospective payments may come at
      a cost. First, there may be a strong incentive for hospitals to choose only low
      severity patients. Second, hospitals may have an incentive to reduce the quality
      of care. I analyze the role of hospital ownership on patient selection and
      quality of care by comparing private nonprofit and public hospitals. The analysis
      is performed by using unique hospital admission data for cardiovascular
      procedures in Norway, covering the period from 1999 to 2006. Matching techniques
      are applied to control for patient heterogeneity. The econometric analyses are
      based on binary probit and ordinary least squares regression models. The results
      indicate that private nonprofit hospitals have specialized in certain procedures.
      These hospitals are also more likely to admit low-severity patients for some
      procedures. The association between quality of care and hospital ownership is
      mixed since private nonprofit hospitals both offer shorter waiting time and
      shorter length of stay.

PMID- 29190538
TI  - Research altruism as motivation for participation in community-centered
      environmental health research.
AB  - Protection of human subjects in research typically focuses on extrinsic rather
      than intrinsic motivations for participation in research. Recent sociological
      literature on altruism suggests that multiple kinds of altruism exist and are
      grounded in a sense of connection to common humanity. We interviewed participants
      in eight community-centered research studies that sampled for endocrine
      disrupting compounds and that shared research findings with participants. The
      results of our analysis of participation in these studies indicate that
      altruistic motivations were commonly held. We found that these sentiments were
      tied to feeling a sense of connection to society broadly, a sense of connection
      to science, or a sense of connection with the community partner organization. We
      develop a new concept of banal altruism to address mundane practices that work
      towards promoting social benefits. Further, we offer that research altruism is a
      specific type of banal altruism that is a multi-faceted and important reason for
      which individuals choose to participate in community-centered research.

PMID- 29190541
TI  - Comparison of moss and pine needles as bioindicators of transboundary polycyclic
      aromatic hydrocarbon pollution in central Japan.
AB  - Atmospheric pollution by polycyclic aromatic hydrocarbons (PAHs) has become a
      serious problem, especially in Asia, as PAHs can severely affect ecologically
      important mountainous areas. Using pine needles and mosses as bio-indicators,
      this study examined PAH pollution in a mountainous study area and evaluated the
      influence of transboundary PAHs. PAHs in urban areas were also evaluated for
      comparison. The study sites were alpine areas and urban areas (inland or coastal
      cities) across central Japan, in the easternmost part of Asia where atmospheric
      pollutants are transported from mainland Asia. The mean PAH concentrations of
      pine needles and mosses were 198.9 +/- 184.2 ng g-1 dry weight (dw) and 131.8 +/-
      60.7 ng g-1 dw (mean +/- SD), respectively. Pine needles preferentially
      accumulated PAHs with low molecular weights (LMW PAHs) and exhibited large
      differences in both PAH concentration and isomer ratios between alpine and urban
      sites. These differences can be explained by the strong influence of LMW PAHs
      emitted from domestic sources, which decreased and changed during transport from
      urban to alpine sites due to dry/wet deposition and photodegradation. In
      contrast, mosses accumulated a higher ratio of PAHs with high molecular weight
      (HMW PAHs). A comparison of isomer ratios showed that the PAH source for alpine
      moss was similar to that for northern coastal cities, which are typically
      influenced by long-transported PAHs from East Asia. Thus, these results indicate
      that alpine moss can also be strongly affected by the transboundary PAHs. It is
      likely that the uptake characteristics of moss, alpine climate, and alpine
      locations far from urban areas can strengthen the influence of transboundary
      pollution. Based on these results, the limitations and most effective use of
      bioindicators of PAH pollution for preserving alpine ecosystems are discussed.

PMID- 29190539
TI  - Dysbiosis of gut microbiota by chronic coexposure to titanium dioxide
      nanoparticles and bisphenol A: Implications for host health in zebrafish.
AB  - Gut microbiota is of critical relevance to host health. However, toxicological
      understanding of environmental pollutants on gut microbiota is limited, not to
      mention their combined effects. In the present study, adult zebrafish (Danio
      rerio) were exposed to titanium dioxide nanoparticles (nano-TiO2; 100 MUg/L),
      bisphenol A (BPA; 0, 2, and 20 MUg/L) or their binary mixtures for three months.
      Sequencing of 16S rRNA amplicons found that nano-TiO2 and BPA coexposure shifted
      the intestinal microbial community, interacting in an antagonistic manner when
      the BPA concentration was low but in a synergistic manner at a higher BPA
      concentration. Sex- and concentration-dependent responses to the coexposure
      regime were also observed for zebrafish growth and intestinal health (e.g.
      neurotransmission, epithelial barrier permeability, inflammation, and oxidative
      stress). Correlation analysis showed that oxidative stress after nano-TiO2 and
      BPA coexposure was tightly associated with the imbalanced ratio of pathogenic
      Lawsonia and normal metabolic Hyphomicrobium, where higher abundance of Lawsonia
      but lower abundance of Hyphomicrobium were induced concurrently. A positive
      relationship was observed between zebrafish body weight and the abundance of
      Bacteroides in the gut, which was also closely associated with the genera of
      Anaerococcus, Finegoldia, and Peptoniphilus. This study revealed, for the first
      time, the combined effects of nano-TiO2 and BPA coexposure on the dynamics of the
      gut microbiome, which proved to have toxicological implications for zebrafish
      host health.

PMID- 29190544
TI  - The contribution of occupational factors on frailty.
AB  - INTRODUCTION: Frailty is a clinical condition characterized by enhanced
      vulnerability to stressors and increased risk of developing dependency and/or
      mortality. It has been described as the multidimensional and dynamic condition
      that cannot be easily disentangled from psychosocial determinants. To date, the
      possible role of occupational factors on frailty development and its progression
      at advanced age are not yet fully understood. The aim of this work is to provide
      a comprehensive overview of existing evidence exploring the relationship between
      multiple occupational issues (e.g., employment history, workplace risk factors,
      organizational job characteristics) and frailty. METHODS: A systematic search and
      revision of available literature addressing the contribution of occupational
      factors on the quantitative and qualitative aspects of frailty in the elderly was
      performed in the Pubmed, Scopus, and ISI Web of Science databases. RESULTS: The
      major weaknesses of existing literature reside in the heterogeneous
      operationalization of frailty and the limited description of the workplace
      factors. Nevertheless, an association between life-course occupational conditions
      and frailty was documented. In particular, intrinsically harder, manual, or blue
      collar occupations emerged as possible determinants of the frailty manifestation
      and severity at older age. CONCLUSIONS: Our preliminary results do not allow
      extrapolating definite conclusions. Further studies are needed. However, it seems
      that a significant relationship exists between the life-course occupation and
      frailty at advanced age. From a public health and social geriatric perspective,
      this work may provide the basis to define future innovations for preventing
      frailty at elderly adopting a life-course approach.

PMID- 29190542
TI  - Reference values and equations reference of balance for children of 8 to 12
      years.
AB  - PURPOSE: There are still no normative data in balance sway for school-age
      children in Brazil. We aimed to establish the reference ranges for balance scores
      and to develop prediction equations for estimation of balance scores in children
      aged 8 to 12 years old. METHODS: The study included 165 healthy children (83 boys
      and 82 girls; age, 8-12 years) recruited from a public school in the city of
      Florianopolis, Santa Catarina, Brazil. We used the Sensory Organization Test to
      assess the balance scores and both a digital scale and a stadiometer to measure
      the anthropometric variables. We tested a stepwise multiple-regression model with
      sex, height, weight, and mid-thigh circumference of the dominant leg as
      predictors of the balance score. RESULTS: For all experimental conditions, girls'
      age accounted for over 85% of the variability in balance scores; while, boys' age
      accounted only 55% of the variability in balance scores. Therefore, balance
      scores increase with age for boys and girls. CONCLUSION: This study described the
      ranges of age- and sex-specific normative values for balance scores in children
      during 6 different testing conditions established by the sensory organization
      test. We confirmed that age was the predictor that best explained the variability
      in balance scores in children between 8 and 12 years old. This study stimulates a
      new and more comprehensive study to estimate balance scores from prediction
      equations for overall Brazilian pediatric population.

PMID- 29190540
TI  - Impact of cold temperature on Euro 6 passenger car emissions.
AB  - Hydrocarbons, CO, NOx, NH3, N2O, CO2 and particulate matter emissions affect air
      quality, global warming and human health. Transport sector is an important source
      of these pollutants and high pollution episodes are often experienced during the
      cold season. However, EU vehicle emissions regulation at cold ambient temperature
      only addresses hydrocarbons and CO vehicular emissions. For that reason, we have
      studied the impact that cold ambient temperatures have on Euro 6 diesel and spark
      ignition (including: gasoline, ethanol flex-fuel and hybrid vehicles) vehicle
      emissions using the World-harmonized Light-duty Test Cycle (WLTC) at -7  degrees
      C and 23  degrees C. Results indicate that when facing the WLTC at 23  degrees C
      the tested vehicles present emissions below the values set for type approval of
      Euro 6 vehicles (still using NEDC), with the exception of NOx emissions from
      diesel vehicles that were 2.3-6 times higher than Euro 6 standards. However,
      emissions disproportionally increased when vehicles were tested at cold ambient
      temperature (-7  degrees C). High solid particle number (SPN) emissions (>1 *
      1011 # km-1) were measured from gasoline direct injection (GDI) vehicles and
      gasoline port fuel injection vehicles. However, only diesel and GDI SPN emissions
      are currently regulated. Results show the need for a new, technology independent,
      procedure that enables the authorities to assess pollutant emissions from
      vehicles at cold ambient temperatures. Harmful pollutant emissions from spark
      ignition and diesel vehicles are strongly and negatively affected by cold ambient
      temperatures. Only hydrocarbon, CO emissions are currently regulated at cold
      temperature. Therefore, it is of great importance to revise current EU winter
      vehicle emissions regulation.

PMID- 29190545
TI  - Six weeks of combined aerobic and resistance exercise using outdoor exercise
      machines improves fitness, insulin resistance, and chemerin in the Korean
      elderly: A pilot randomized controlled trial.
AB  - BACKGROUND: The aim of this study was to investigate the effect of a six-week
      long exercise program using outdoor exercise equipment on fitness, insulin
      resistance and adipocytokines among Korean elderly. METHODS: A total of 47
      participants were randomized into one of the following three groups; control,
      resistance exercise or combined exercise (aerobic and resistance exercise). The
      resistance exercise group completed three resistance types of exercise. The
      combined exercise group completed five exercises, including three resistance
      types of exercise and two aerobic types of exercise. Participants' body
      composition, fitness level, homeostasis model assessment of insulin resistance
      (HOMA-IR), and adipocytokines were measured at baseline and at the end of six
      weeks. RESULTS: After six weeks of exercise training, participants in the
      combined exercise group exhibited significant reduction in insulin, HOMA-IR and
      chemerin levels, while significant reduction was observed in HOMA-IR only in the
      resistance exercise group compared with the control group. Meanwhile, six weeks
      of exercise training, whether resistance exercise alone or combined,
      significantly improved upper body muscular strength/endurance and physical
      function compared to the control group. CONCLUSIONS: Six weeks of combined
      exercise using outdoor exercise equipment was effective in improving fitness,
      HOMA-IR, circulating chemerin levels, and other known risk factors of chronic
      diseases.

PMID- 29190547
TI  - Low-folate stress reprograms cancer stem cell-like potentials and bioenergetics
      metabolism through activation of mTOR signaling pathway to promote in vitro
      invasion and in vivo tumorigenicity of lung cancers.
AB  - Low-folate (LF) nutritional status is associated with increased risks of lung
      cancer. It has unexplored effects on lung cancer malignancy, a cancer stem cell
      (CSC) disease. We hypothesized that LF may reprogram CSC-like potential and
      bioenergetics metabolism to increase metastasis potential of lung cancers.
      Cultivation of human non-small-cell lung cancer cells (H23) in an LF medium
      enhanced CSC-like properties signified by increased expressions of the CSC
      surface marker CD44 and pluripotency markers Sox2, Oct4 and ALDH1A1, and promoted
      self-renewal ability of anchorage-independent oncospheroid formation. The CSC
      like phenotype of LF-treated H23 cells coupled with the metabolic reprogramming
      to aerobic glycolysis evident by elevated lactate release and medium
      acidification suppressed expressions of pyruvate dehydrogenase E1-alpha, and
      elevated redox status of the NADH/NAD+ and NADPH/NADP+ ratios. The LF-induced
      metabostemness phenotype of H23 cells was modified by DNA methylation inhibitor 5
      AdC and histone acetylation inhibitor EX. Treatment of H23 cells with mTOR siRNA
      or the mTOR inhibitor rapamycin abrogated LF-activated Akt-mTOR-Hif1-Foxo
      signaling and stemness-associated sonic hedgehog pathway, reversed Warburg
      metabolic switch and diminished invasion of H23 cells. Intrapleural injection of
      LF-induced lung oncospheres into the LF recipient mice, but not the control
      recipient mice, caused metastasis xenograft lung tumors. The in vitro and in vivo
      data corroboratively demonstrate that LF stress reprograms metabostemness
      signatures through activated mTOR signaling pathway to promote metastasis
      tumorigenicity of lung cancers.

PMID- 29190548
TI  - Supplementation with polyunsaturated fatty acids in pregnant rats with mild
      diabetes normalizes placental PPARgamma and mTOR signaling in female offspring
      developing gestational diabetes.
AB  - Maternal diabetes impairs fetoplacental development and programs metabolic
      diseases in the offspring. We have previously reported that female offspring of
      pregnant rats with mild diabetes develop gestational diabetes mellitus (GDM) when
      they become pregnant. Here, we studied the effects of supplementation with
      polyunsaturated fatty acids (PUFAs) in pregnant mild diabetic rats (F0) by
      feeding a 6% safflower-oil-enriched diet from day 1 to 14 followed by a 6% chia
      oil-enriched diet from day 14 of pregnancy to term. We analyzed maternal
      metabolic parameters and placental signaling at term in pregnant offspring (F1).
      The offspring of both PUFAs-treated and untreated mild diabetic rats developed
      GDM. Although gestational hyperglycemia was not prevented by dietary PUFAs
      treatment in F0, triglyceridemia and cholesterolemia in F1 mothers were
      normalized by F0 PUFAs dietary treatment. In the placenta of F1 GDM rats,
      PPARgamma levels were reduced and lipoperoxidation was increased, changes that
      were prevented by the maternal diets enriched in PUFAs in the F0 generation.
      Moreover, fetal overgrowth and placental activation of mTOR signaling pathways
      were reduced in F1 GDM rats whose mothers were treated with PUFAs diets. These
      results suggest that F0 PUFAs dietary treatment in pregnancies with mild diabetes
      improves maternal dyslipidemia, fetal overgrowth and placental signaling in
      female offspring when they become pregnant. We speculate that an increased PUFAs
      intake in pregnancies complicated by diabetes may prove effective to ameliorate
      metabolic programming in the offspring, thereby improving the health of future
      generations.

PMID- 29190546
TI  - Age related changes in balance performance during self-selected and narrow stance
      testing.
AB  - BACKGROUND: Various balance tests have been considered as fall risk screening
      tools however there is a lot of variability in the methods and outcome measures
      reported. Based on previous research examining age-related changes in balance and
      differences between fallers and nonfallers, the purpose of this investigation was
      to examine age-related balance changes, as reflected in medial-lateral center of
      pressure (CP) velocity, in community-dwelling/independently living adults
      (>=60years) during self-selected and narrow stance testing with eyes opened and
      closed. METHODS: Two hundred and thirty adults aged 60yrs or older completed one
      45s trial under two stances (self-selected, narrow) and two visual conditions
      (eyes opened, eyes closed). Average medial-lateral CP velocity was computed from
      the CP data, with preliminary analysis demonstrating positive skewness and
      association with body height. A sway velocity index (SVI) was created by a
      natural logarithm transformation and dividing by body height. Multiple linear
      regression was used to determine the association between age, visual condition,
      stance, and sex with SVI. RESULTS: Age, visual condition, stance and sex were all
      demonstrated to be significant predictors of SVI, with the combination of the
      predictors explaining 25% of the variance in the SVI. CONCLUSIONS: These results
      confirm the balance testing protocol and SVI to be sensitive to age-related
      changes in balance performance. The results of this study should help future
      research aimed towards establishing a quick, easy to administer, and readily
      interpretable instrumented test for assisting with identifying potential balance
      impairments in older adults who have yet to demonstrate outward deficits.

PMID- 29190549
TI  - Cholesterol oversynthesis markers define familial combined hyperlipidemia versus
      other genetic hypercholesterolemias independently of body weight.
AB  - Primary hypercholesterolemia of genetic origin, negative for mutations in LDLR,
      APOB, PCSK9 and APOE genes (non-FH GH), and familial combined hyperlipidemia
      (FCHL) are polygenic genetic diseases that occur with hypercholesterolemia, and
      both share a very high cardiovascular risk. In order to better characterize the
      metabolic abnormalities associated with these primary hypercholesterolemias, we
      used noncholesterol sterols, as markers of cholesterol metabolism, to determine
      their potential differences. Hepatic cholesterol synthesis markers (desmosterol
      and lanosterol) and intestinal cholesterol absorption markers (sitosterol and
      campesterol) were determined in non-FH GH (n=200), FCHL (n=100) and genetically
      defined heterozygous familial hypercholesterolemia subjects (FH) (n=100) and in
      normolipidemic controls (n=100). FCHL subjects had lower cholesterol absorption
      and higher cholesterol synthesis than non-FH GH, FH and controls (P<.001). When
      noncholesterol sterols were adjusted by body mass index (BMI), FCHL subjects had
      higher cholesterol synthesis than non-FG GH, FH and controls (P<.001). An
      increase in BMI was accompanied by increased cholesterol synthesis and decreased
      cholesterol absorption in non-FH GH, FH and controls. However, this association
      between BMI and cholesterol synthesis was not observed in FCHL. Non-high-density
      lipoprotein cholesterol showed a positive correlation with cholesterol synthesis
      markers similar to that of BMI in non-FH GH, FH and normolipemic controls, but
      there was no correlation in FCHL. These results suggest that FCHL and non-FH GH
      have different mechanisms of production. Cholesterol synthesis and absorption are
      dependent of BMI in non-FH GH, but cholesterol synthesis is increased as a
      pathogenic mechanism in FCHL independently of age, gender, APOE and BMI.

PMID- 29190553
TI  - Sewage sludge as a soil amendment in a Larix decidua plantation: Effects on tree
      growth and floristic diversity.
AB  - Sewage sludge application in forest plantations is an interesting complementary
      alternative practice to sewage sludge reutilization and recycling, with a
      significant and sustainable net effect in climate change mitigation. However, to
      optimize it a detailed knowledge of its effects on ecosystem components such as
      plants, soil, water and fauna is needed. We investigated the effects of sewage
      sludge application on soil, tree growth and floristic diversity in a ten-year-old
      plantation of European larch (Larix decidua Mill.). Our one-hectare study site,
      located at Melisey, Haute-Saone, France (47 degrees 753' Lat., 6 degrees 580'
      Long.), was subdivided into six plots. Three plots, alternating with three
      control plots (no sewage sludge application), were amended in June 2008 with
      0.4tDWha-1 obtained from a municipal urban wastewater treatment plant in Melisey.
      Within each plot, one subplot was delimited and sludge was again manually applied
      at 3t of DWha-1 in July 2009 and March 2010 to the soil surface of the amended
      subplots without incorporation. The results showed no effect on radial and height
      growth of European larch amended with 0.4tDWha-1. While a significant temporary
      increase in pH, macro-element contents (N, P and Ca) and the trace metal (Cu and
      Zn) concentration in the soil was observed, it had no significant effect on
      needles and sporocarp contents. The number of species in the amended subplots
      with 3tDWha-1year-1 increased by 80% compared to the control. However, the
      relative species abundance present only in amended subplots remains <1, except
      for Hypericum humifusum.

PMID- 29190550
TI  - Green tea extract protects against hepatic NFkappaB activation along the gut
      liver axis in diet-induced obese mice with nonalcoholic steatohepatitis by
      reducing endotoxin and TLR4/MyD88 signaling.
AB  - Green tea extract (GTE) reduces NFkappaB-mediated inflammation during
      nonalcoholic steatohepatitis (NASH). We hypothesized that its anti-inflammatory
      activities would be mediated in a Toll-like receptor 4 (TLR4)-dependent manner.
      Wild-type (WT) and loss-of-function TLR4-mutant (TLR4m) mice were fed a high-fat
      diet containing GTE at 0 or 2% for 8 weeks before assessing NASH, NFkappaB
      mediated inflammation, TLR4 and its adaptor proteins MyD88 and TRIF, circulating
      endotoxin, and intestinal tight junction protein mRNA expression. TLR4m mice had
      lower (P<.05) body mass compared with WT mice but similar adiposity, whereas body
      mass and adiposity were lowered by GTE regardless of genotype. Liver steatosis,
      serum alanine aminotransferase, and hepatic lipid peroxidation were also lowered
      by GTE in WT mice, and were similarly lowered in TLR4m mice regardless of GTE.
      Phosphorylation of the NFkappaB p65 subunit and pro-inflammatory genes (TNFalpha,
      iNOS, MCP-1, MPO) were lowered by GTE in WT mice, and did not differ from the
      lowered levels in TLR4m mice regardless of GTE. TLR4m mice had lower TLR4 mRNA,
      which was also lowered by GTE in both genotypes. TRIF expression was unaffected
      by genotype and GTE, whereas MyD88 was lower in mice fed GTE regardless of
      genotype. Serum endotoxin was similarly lowered by GTE regardless of genotype.
      Tight junction protein mRNA levels were unaffected by genotype. However, GTE
      similarly increased claudin-1 mRNA in the duodenum and jejunum and mRNA levels of
      occludin and zonula occluden-1 in the jejunum and ileum. Thus, GTE protects
      against inflammation during NASH, likely by limiting gut-derived endotoxin
      translocation and TLR4/MyD88/NFkappaB activation.

PMID- 29190551
TI  - Predictors and correlations of phthalate metabolite concentrations in urine and
      seminal plasma among reproductive-aged men.
AB  - BACKGROUND: Certain phthalates are suspected to be endocrine disruptors that are
      adversely associated with male reproductive health. However, the predictors and
      correlations of phthalate metabolite concentrations in urine and seminal plasma
      among reproductive-aged men have not been thoroughly studied. OBJECTIVE: To
      investigate the predictors and correlations of phthalate metabolite
      concentrations in urine and seminal plasma among adult Chinese males. METHOD: We
      measured mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monomethyl
      phthalate (MMP), monoethyl phthalate (MEP), mono-n-octyl phthalate (MOP), mono(2
      ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and
      mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) concentrations in seminal plasma and
      repeated spot-urine samples from 687 men who visited a reproductive center. Mixed
      effect models were used to examine the associations of sociodemographic,
      lifestyle and medical factors with urinary metabolite concentrations. Linear
      regression models were used to identify predictors of metabolite concentrations
      in seminal plasma and correlations between metabolite concentrations in spot
      urine samples and seminal plasma. RESULTS: Measurements taken from spot urine
      samples poorly predicted same-day seminal plasma concentrations (all R2<0.10).
      Inverse associations were observed between education level and urinary MBP and
      MEOHP and between household income and urinary MMP; receiving intravenous
      infusion therapy was associated with increased urinary MBP, MEHHP and MEOHP, use
      of facial cleanser/cream was associated with increased MEP, and smoking was
      associated with increased MEHP. The predictors of metabolite concentrations in
      seminal plasma differed from those in urine, except for the association of
      intravenous infusion therapy with MBP. BMI was associated with increased seminal
      plasma MBP, MEHP and MEOHP, smoking was associated with increased MEP, and
      contact with plastics was associated with increased MEOHP. CONCLUSIONS: Phthalate
      metabolite concentrations in adult men varied in accordance with sociodemographic
      variables, lifestyle factors and intravenous therapy. Measures of metabolite
      levels in urine may not directly reflect the exposure status of the male
      reproductive system.

PMID- 29190556
TI  - Null-space Monte Carlo particle tracking to assess groundwater PCE
      (Tetrachloroethene) diffuse pollution in north-eastern Milan functional urban
      area.
AB  - The Lombardy Region in Italy is one of the most urbanized and industrialized
      areas in Europe. The presence of countless sources of groundwater pollution is
      therefore a matter of environmental concern. The sources of groundwater
      contamination can be classified into two different categories: 1) Point Sources
      (PS), which correspond to areas releasing plumes of high concentrations (i.e. hot
      spots) and 2) Multiple-Point Sources (MPS) consisting in a series of
      unidentifiable small sources clustered within large areas, generating an
      anthropogenic diffuse contamination. The latter category frequently predominates
      in European Functional Urban Areas (FUA) and cannot be managed through standard
      remediation techniques, mainly because detecting the many different source areas
      releasing small contaminant mass in groundwater is unfeasible. A specific
      legislative action has been recently enacted at Regional level (DGR IX/3510
      2012), in order to identify areas prone to anthropogenic diffuse pollution and
      their level of contamination. With a view to defining a management plan, it is
      necessary to find where MPS are most likely positioned. This paper describes a
      methodology devised to identify the areas with the highest likelihood to host
      potential MPS. A groundwater flow model was implemented for a pilot area located
      in the Milan FUA and through the PEST code, a Null-Space Monte Carlo method was
      applied in order to generate a suite of several hundred hydraulic conductivity
      field realizations, each maintaining the model in a calibrated state and each
      consistent with the modelers' expert-knowledge. Thereafter, the MODPATH code was
      applied to generate back-traced advective flowpaths for each of the models built
      using the conductivity field realizations. Maps were then created displaying the
      number of backtracked particles that crossed each model cell in each stochastic
      calibrated model. The result is considered to be representative of the FUAs areas
      with the highest likelihood to host MPS responsible for diffuse contamination.

PMID- 29190555
TI  - Sources and distribution of yttrium and rare earth elements in surface sediments
      from Tagus estuary, Portugal.
AB  - The distribution and sources of yttrium and rare-earth elements (YREE) in surface
      sediments were studied on 78 samples collected in the Tagus estuary (SW Portugal,
      SW Europe). Yttrium and total REE contents ranged from 2.4 to 32mg.kg-1 and 18 to
      210mg.kg-1, respectively, and exhibited significant correlations with sediment
      grain-size, Al, Fe, Mg and Mn, suggesting a preferential association to fine
      grained material (e.g. aluminosilicates but also Al hydroxides and Fe
      oxyhydroxides). The PAAS (Post-Archean Australian Shale) normalized patterns
      display three distinct YREE fractionation pattern groups along the Tagus estuary:
      a first group, characterized by medium to coarse-grained material, a depleted and
      almost flat PAAS-normalized pattern, with a positive anomaly of Eu, representing
      one of the lithogenic components; a second group, characterized mainly by fine
      grained sediment, with higher shale-normalized ratios and an enrichment of LREE
      relative to HREE, associated with waste water treatment plant (WWTP) outfalls,
      located in the northern margin; and, a third group, of fine-grained material,
      marked by a significant enrichment of Y, a depletion of Ce and an enrichment of
      HREE over LREE, located near an inactive chemical-industrial complex (e.g. pyrite
      roast plant, chemical and phosphorous fertilizer industries), in the southern
      margin. The data allow the quantification of the YREE contents and its spatial
      distribution in the surface sediments of the Tagus estuary, identifying the main
      potential sources and confirming the use of rare earth elements as tracers of
      anthropogenic activities in highly hydrodynamic estuaries.

PMID- 29190552
TI  - Evaluation of local anesthetic effects of Lidocaine-Ibuprofen ionic liquid
      stabilized silver nanoparticles in Male Swiss mice.
AB  - A simple approach for the synthesis of Lidocaine-Ibuprofen ionic liquid
      stabilized silver nanoparticles (IL-AgNPs) was reported in this work. The shape,
      size and surface morphology of the Lidocaine-Ibuprofen ionic liquid stabilized
      AgNPs were characterized by using spectroscopic and microscopic techniques such
      as Ultraviolet-visible spectroscopy (UV-Visible), X-ray diffraction (XRD)
      analysis, Selected area electron diffraction (SAED), Transmission electron
      microscopy (TEM). TEM analysis showed the formation of 20-30nm size of IL-AgNPs
      with very clear lattice fringes. SAED pattern confirmed the highly crystalline
      nature of fabricated IL stabilized AgNPs. EDS results confirmed the formation of
      nanosilver. The fabricated IL-AgNPs were studied for their local anesthetic
      effect in rats. The results of local anesthetic effect showed that the time for
      onset of action by IL-AgNPs is 10min, which is significantly higher than that for
      EMLA. Further, tactile test results confirmed the stronger and faster local
      anesthetic effect of IL-AgNPs when compared to that of EMLA.

PMID- 29190554
TI  - A potential microRNA regulation of immune-related genes in invertebrate
      haemocytes.
AB  - Bivalve mollusks have been employed as sentinel organisms in environmental health
      programs due to their sedentary lifestyle, filter-feeding behavior and their
      ability to accumulate pathogens or toxin molecules inside tissues. Endocrine
      disrupting chemicals (EDCs) can be up taken and bioaccumulated, and due to
      sensibility of mollusks to these EDCs, being able to cause immune alterations.
      Recently, microRNAs (miRNAs) were shown to be involved in modulation and
      buffering developmental processes against the effects of environmental
      alterations and pathogenic microorganisms. Moreover, it is suggested that this
      miRNAs are incorporated into the estrogen-controlled immune network, regulating
      mechanism of immune gene expression at the posttranscriptional level, modulating
      immune responses as phagocytosis, redox reaction and apoptosis in bivalve
      haemocytes. Thus, miRNAs can be used as biomarkers that specifically elucidate
      immunotoxic effects caused by exogenous biotic or abiotic factors, and can act as
      useful tools in integrated monitoring environmental health programs. In this
      review, we aim to describe the investigations that have been carried out on
      miRNAs in bivalve mollusks, especially those associated with immune responses
      against infectious agents and xenobiotic exposure.

PMID- 29190557
TI  - Prenatal co-exposure to neurotoxic metals and neurodevelopment in preschool
      children: The Environment and Childhood (INMA) Project.
AB  - We sought to determine whether prenatal co-exposure to As, Cd, Hg, Mn, and Pb was
      associated with impaired neurodevelopment in preschool children from the Spanish
      Environment and Childhood (INMA) Project, using the placenta as exposure matrix.
      We measured metal levels in placenta tissue samples randomly selected from five
      of the seven population-based birth cohorts participating in the INMA Project,
      collected between 2000 and 2008. Neuropsychological assessment of cognitive and
      motor function was carried through the use of the McCarthy Scales of Children's
      Abilities (MSCA) at the age of 4-5years. Data on placental metal levels, MSCA
      scores, and relevant covariates was available for 302 children. Mn was detected
      in all placental samples, Cd in nearly all placentas (99%) and As, Hg, and Pb in
      22%, 58%, and 17% of the placentas, respectively. After adjusting for potential
      confounders, detectable As levels were associated with decrements in global and
      verbal executive functions and quantitative abilities; detectable Hg was
      associated with lower scores on the verbal function of posterior cortex in a dose
      response manner, and non-linearly related to poorer motor function and gross
      motor skills; and Mn levels were associated with decrement in perceptual
      performance skills in a dose-response manner but with better memory span and
      quantitative skills. A synergistic interactive effect was found between As and Pb
      with respect to the general cognitive score, whereas an antagonistic interaction
      was found between Mn and Hg. Prenatal exposure to As and Hg may be a risk factor
      for cognitive and motor impairment in children, while the effects of Cd and Mn on
      neurodevelopment are less clear. Future studies should examine combined and
      interactive effects of exposure to multiple metals during vulnerable periods of
      brain development prospectively.

PMID- 29190561
TI  - Labile and stable soil organic carbon and physical improvements using
      groundcovers in vineyards from central Spain.
AB  - Mediterranean vineyards are usually managed with continuous tillage to maintain
      bare soils leading to low organic matter stocks and soil degradation. Vineyards
      are part of the Mediterranean culture, their management can be sustainable. We
      propose the setup of two types of groundcovers with the aim to assess their
      potential influence to improve soil properties. A field trial was performed to
      compare the effects of a seeded (Brachypodium distachyon) and spontaneous
      groundcovers, on a set of soil parameters, in comparison with the traditional
      tillage in four vineyards located in the center of Spain. Three years after the
      groundcovers establishment soil organic carbon stocks increased up to 1.62 and
      3.18Mgha-1 for the seeded and the spontaneous groundcovers, respectively,
      compared to conventional tillage. Both labile and stable fractions improved their
      soil organic carbon content with the use of groundcovers, particularly the labile
      fraction. Moreover, soil structure and functional soil properties improved
      through better aggregate stability, pore connectivity and infiltration rates. The
      higher root biomass input of the spontaneous groundcovers derived in higher soil
      organic carbon increases and soil quality improvement. Consequently, under low
      rainfall conditions (<400mmperyear) spontaneous vegetation, properly managed
      according to site conditions, is an effective soil management strategy to revert
      soil degradation and increase soil quality in Mediterranean vineyards.

PMID- 29190559
TI  - Environmental effects by introducing Potamogeton crispus to recover a eutrophic
      Lake.
AB  - Re-establishing submerged vegetation is considered an important tool to restore
      shallow eutrophic lakes. A whole year comparative field study was performed in a
      eutrophic lake and its connected pond with Potamogeton crispus in order to
      determine the effects of the growth and senescence of submerged macrophytes on
      structure of phytoplankton. P. crispus improved the water quality at the growing
      season in terms of improving transparency, decreasing total phosphorus, soluble
      reactive phosphorus (SRP) and chlorophyll a concentrations and slowering turnover
      rate of dissolved organic phosphorus (DOP). Meanwhile, dominant species shift
      from Chlorophyta to Diatom. Notably, senescence and decomposition of P. crispus
      in late spring resulted in an abrupt increase of DOP, providing a suitable
      growing environment for Euglena and dinoflagellates and a Peridiniopsis bloom
      occurred owing to their advantage in utilizing DOP. Peridiniopsis excreted
      phosphatase as evidence by simultaneously in situ enzyme labelled fluorescence
      (ELF) labelling and main alkaline phosphatase activity contributed by large
      particles, suggesting that the dominance of dinoflagellate with low SRP is
      enabled by its ability to efficiently hydrolyze DOP. Under the scenario of
      worldwide application of re-establishing submerged vegetation, our results
      provide the evidence of the negative environmental effects that occurred when
      transplanting P. crispus to recover a eutrophic lake.

PMID- 29190543
TI  - Scutellarin alleviates lipopolysaccharide-induced cognitive deficits in the rat:
      Insights into underlying mechanisms.
AB  - Inflammation is a common hallmark of neurodegenerative disorders. Systemic
      inflammation is usually associated with cognitive deficits. Scutellarin is a
      flavone with established antioxidant, anti-inflammatory, and neuroprotective
      effects. In this study, the effect of this flavone in prevention of
      lipopolysaccharide (LPS)-induced cognitive deficit was evaluated. LPS was i.p.
      injected at a dose of 500MUg/kg/day and scutellarin was administered i.p. at
      doses of 5, 25, or 50mg/kg/day. Treatment of LPS-injected rats with scutellarin
      dose-dependently ameliorated deficits of spatial recognition memory in Y maze,
      discrimination index in novel object discrimination task, and retention and
      recall index in passive avoidance test. Additionally, scutellarin lowered
      hippocampal malondialdehyde (MDA) and potentiated antioxidant defense elements
      comprising superoxide dismutase (SOD), catalase, and glutathione (GSH) in
      addition to reduction of acetylcholinesterase (AChE) activity. Furthermore,
      scutellarin decreased hippocampal nuclear factor-kappaB (NF-kappaB), tumor
      necrosis factor alpha (TNFalpha), interleukin 6 (IL-6) and elevated nuclear
      factor (erythroid-derived 2)-like 2 (Nrf2). Inappropriate alterations of
      authophagy markers including beclin-1, LC3 II, mTOR, and P62 were also prevented
      in the presence of scutellarin. Our findings demonstrate that scutellarin
      alleviates LPS-induced cognitive disturbances, however, the precise mechanism
      remains still speculative.

PMID- 29190560
TI  - Methylmercury complexes: Selection of thermodynamic properties and application to
      the modelling of a column experiment.
AB  - Complexation with methyl groups produces the most toxic form of mercury,
      especially because of its capacity to bioconcentrate in living tissues.
      Understanding and integrating methylation and demethylation processes is of the
      utmost interest in providing geochemical models relevant for environmental
      assessment. In a first step, we investigated methylation at equilibrium, by
      selecting the thermodynamic properties of different complexes that form in the
      chemical system Hg-SO3-S-Cl-C-H2O. The selection included temperature
      dependencies of the equilibrium constants when available. We also considered
      adsorption and desorption reactions of both methylated and non-methylated mercury
      onto mineral surfaces. Then we assessed the kinetics of methylation by comparing
      a dedicated column experiment with the results of a geochemical model, including
      testing different methylation and demethylation kinetic rate laws. The column
      system was a simple medium: silicic sand and iron hydroxides spiked with a
      mercury nitrate solution. The modelling of methylmercury production with two
      different rate laws from the literature is bracketing the experimental results.
      Dissolved mercury, iron and sulfate concentrations were also correctly
      reproduced. The internal evolution of the column was also correctly modeled,
      including the precipitation of mackinawite (FeS) and the evolution of dissolved
      iron. The results validate the conceptual model and underline the capacity of
      geochemical models to reproduce some processes driven by bacterial activity.

PMID- 29190558
TI  - Factors controlling the three-decade long rise in cyanobacteria biomass in a
      eutrophic shallow lake.
AB  - We aimed at quantifying the importance of limnological variables in the decadal
      rise of cyanobacteria biomass in shallow hemiboreal lakes. We constructed
      estimates of cyanobacteria (blue-green algae) biomass in a large, eutrophic lake
      (Estonia, Northeastern Europe) from a database comprising 28 limnological
      variables and spanning more than 50years of monitoring. Using a dual-model
      approach consisting in a boosted regression trees (BRT) followed by a generalized
      least squares (GLS) model, our results revealed that six variables were most
      influential for assessing the variance of cyanobacteria biomass. Cyanobacteria
      response to nitrate concentration and rotifer abundance was negative, whereas it
      was positive to pH, temperature, cladoceran and copepod biomass. Response to
      total phosphorus (TP) and total phosphorus to total nitrogen ratio was very weak,
      which suggests that actual in-lake TP concentration is still above limiting
      values. The most efficient GLS model, which explained nearly two thirds (r2=0.65)
      of the variance of cyanobacteria biomass included nitrate concentration, water
      temperature and pH. The very high number of observations (maximum n=525) supports
      the robustness of the models. Our results suggest that the decadal rise of blue
      green algae in shallow lakes lies in the interaction between cultural
      eutrophication and global warming which bring in-lake physical and chemical
      conditions closer to cyanobacteria optima.

PMID- 29190562
TI  - Indoor thermal environment, air exchange rates, and carbon dioxide concentrations
      before and after energy retro fits in Finnish and Lithuanian multi-family
      buildings.
AB  - Impacts of energy retrofits on indoor thermal environment, i.e. temperature (T)
      and relative humidity (RH), as well as ventilation rates and carbon dioxide (CO2)
      concentrations, were assessed in 46 Finnish and 20 Lithuanian multi-family
      buildings, including 39 retrofitted case buildings in Finland and 15 in Lithuania
      (the remaining buildings were control buildings with no retrofits). In the
      Finnish buildings, high indoor T along with low RH levels was commonly observed
      both before and after the retrofits. Ventilation rates (l/s per person) were
      higher after the retrofits in buildings with mechanical exhaust ventilation than
      the corresponding values before the retrofits. Measured CO2 levels were low in
      vast majority of buildings. In Lithuania, average indoor T levels were low before
      the retrofits and there was a significant increase in the average T after the
      retrofits. In addition, average ventilation rate was lower and CO2 levels were
      higher after the retrofits in the case buildings (N=15), both in apartments with
      natural and mixed ventilation. Based on the results, assessment of thermal
      conditions and ventilation rates after energy retrofits is crucial for optimal
      indoor environmental quality and energy use.

PMID- 29190563
TI  - Institutional impediments to conservation of freshwater dependent ecosystems.
AB  - When freshwater resources become scarce there is a trade-off between human
      resource demands and environmental sustainability. The cost of conserving
      freshwater ecosystems can potentially be reduced by implementing institutional
      reforms that endow environmental water managers with a permanent water
      entitlement and the capacity to store, trade and release water. Australia's
      Murray Darling Basin Plan (MDBP) includes one of the world's most ambitious
      programs to recover water for the environment, supported by institutional reforms
      that allow environmental water managers to operate in water markets. One of the
      anticipated benefits of the Plan is to improve the health of flood-dependent
      forests, which are among the most endangered ecosystems globally because of river
      regulation and land clearance. However, periodic flooding to conserve floodplain
      ecosystems in the MDB creates losses to riparian landowners such as damage to
      fencing and temporary loss of access to flooded land. To reduce these losses
      reservoir operators restrict daily water release volumes. Using a model of
      optimal water management in Australia's southern MDB we estimate that current
      reservoir operating restrictions will substantially reduce the ecological
      benefits of investments made to recover water for the environment. The reduction
      in benefits is largest if floodplain forests decline rapidly without periodic
      inundation. In the latter circumstances, ecological losses cannot significantly
      be reduced by allowing environmental water managers to operate in water markets.
      Our findings demonstrate that the recovery of large volumes of water for
      environmental purposes and water market reforms are insufficient for conserving
      flood-dependent ecosystems without coordination and cooperation among multiple
      stakeholders responsible for water and land management.

PMID- 29190564
TI  - Application of microwave-pretreated cephalosporin mycelial dreg (CMD) as soil
      amendment: Temporal changes in chemical and fluorescent parameters of soil
      organic matter.
AB  - Land application of treated cephalosporin mycelial dreg (CMD) as a soil amendment
      is an alternative to its disposal in landfills and incineration because it has
      environmental and agronomic benefits. This study validated the efficacy of using
      the dewatered, microwave-pretreated CMD as a soil amendment. Pot experiments were
      conducted to assess the temporal changes in soil organic matter (SOM) profiles
      via chemical and fluorescent parameters. During the ageing period, the CMD
      treated soil experienced a sudden rise in soil pH and soil electrical
      conductivity, along with a rapid decline in soil organic carbon and soil organic
      nitrogen content. The specific Ex/Em peak related to protein-like substances
      gradually disappeared, while those related to humic acid-like substances
      continued to increase thereafter. Fluorescence regional integration (FRI) results
      showed an ascended PV,n/PIII,n index (1.94) and significant correlations with
      chemical data (M2=0.2875, r=0.8441, P<0.001, 999 permutations for Procrustes
      analysis). Taken together, despite the temporal changes in chemical and
      fluorescent data after soil conditioning, the increased content of SOM containing
      humic acid-like substances was observed at the end of the incubation period
      compared with control soil samples, indicating that the microwave-pretreated CMD
      might be applied as a soil amendment.

PMID- 29190567
TI  - Simulating emissions of 1,3-dichloropropene after soil fumigation under field
      conditions.
AB  - Soil fumigation is an important agricultural practice used to produce many
      vegetable and fruit crops. However, fumigating soil can lead to atmospheric
      emissions which can increase risks to human and environmental health. A complete
      understanding of the transport, fate, and emissions of fumigants as impacted by
      soil and environmental processes is needed to mitigate atmospheric emissions.
      Five large-scale field experiments were conducted to measure emission rates for
      1,3-dichloropropene (1,3-D), a soil fumigant commonly used in California.
      Numerical simulations of these experiments were conducted in predictive mode
      (i.e., no calibration) to determine if simulation could be used as a substitute
      for field experimentation to obtain information needed by regulators. The results
      show that the magnitude of the volatilization rate and the total emissions could
      be adequately predicted for these experiments, with the exception of a scenario
      where the field was periodically irrigated after fumigation. In addition, the
      timing of the daily peak 1,3-D emissions was not accurately predicted for these
      experiments due to the peak emission rates occurring during the night or early
      morning hours. This study revealed that more comprehensive mathematical models
      (or adjustments to existing models) are needed to fully describe emissions of
      soil fumigants from field soils under typical agronomic conditions.

PMID- 29190570
TI  - Grooving of nanoparticles using sublimable liquid crystal for transparent
      omniphobic surface.
AB  - Hierarchical assembly of nanoparticles (NPs) is of interest for omniphobic
      surfaces in the way that hierarchical scale roughness possibly provides effective
      liquid repellency and also it is relatively easy to build large-area coatings via
      the bottom-up assembly process. However, all NP assemblies often lacks mechanical
      robustness. Hence, the development of the effective fabrication method to make
      well-deposited hierarchical NPs assembly is demanded. In this report, we have
      demonstrated an all-NP three-dimensional hierarchical surface that is omniphobic
      yet highly transparent and mechanically robust. By taking advantage of
      sublimation and recondensation of smectic A liquid crystals (LCs) in a simple
      thermal annealing process, we patterned NP aggregates in one-dimensional grooves
      directed by LCs. The resultant groove-like NP-assembled surface showed
      omniphobicity, repelling water, glycerol, ethylene glycol, and olive oil (with
      contact angle of 156.5 degrees , 147 degrees , 136.5 degrees , and 123.2 degrees
      , respectively) because of the low surface energy of the fluorinated NPs and dual
      roughness. The coating is highly transparent with ~90% transmittance in the
      visible wavelength. We investigate the mechanical robustness of the all NP
      coatings by sand abrasion, which shows nearly identical omniphobicity and
      transparency after the sand abrasion.

PMID- 29190565
TI  - Contrasting responses of soil respiration and temperature sensitivity to land use
      types: Cropland vs. apple orchard on the Chinese Loess Plateau.
AB  - Land use plays an essential role in regional carbon cycling, potentially
      influencing the exchange rates of CO2 flux between soil and the atmosphere in
      terrestrial ecosystems. Temperature sensitivity of soil respiration (Q10), as an
      efficient parameter to reflect the possible feedback between the global carbon
      cycle and climate change, has been extensively studied. However, very few reports
      have assessed the difference in temperature sensitivity of soil respiration under
      different land use types. In this study, a three-year field experiment was
      conducted in cropland (winter wheat, Triticum aestivum L.) and apple orchard
      (Malus domestica Borkh) on the semi-arid Loess Plateau from 2011 to 2013. Soil
      respiration (measured using Li-Cor 8100), bacterial community structure
      (represented by 16S rRNA), soil enzyme activities, and soil physicochemical
      properties of surface soil were monitored. The average annual soil respiration
      rate in the apple orchard was 12% greater than that in the cropland (2.01 vs.
      1.80MUmolm-2s-1), despite that the average Q10 values in the apple orchard was
      15% lower than that in the cropland (ranging from 1.63 to 1.41). As to the
      differences among predominant phyla, Proteobacteria was 26% higher in the apple
      orchard than that in the cropland, whereas Actinobacteria and Acidobacteria were
      18% and 36% lower in the apple orchard. The beta-glucosidase and
      cellobiohydrolase activity were 15% (44.92 vs. 39.09nmolh-1g-1) and 22% greater
      (21.39 vs. 17.50nmolh-1g-1) in the apple orchard than that in the cropland.
      Compared to the cropland, the lower Q10 values in the apple orchard resulted from
      the variations of bacterial community structure and beta-glucosidase and
      cellobiohydrolase activity. In addition, the lower C: N ratios in the apple
      orchard (6.50 vs. 8.40) possibly also contributed to its lower Q10 values. Our
      findings call for further studies to include the varying effects of land use
      types into consideration when applying Q10 values to predict the potential CO2
      efflux feedbacks between terrestrial ecosystems and future climate scenarios.

PMID- 29190566
TI  - Life cycle and hydrologic modeling of rainwater harvesting in urban
      neighborhoods: Implications of urban form and water demand patterns in the US and
      Spain.
AB  - Water management plays a major role in any city, but applying alternative
      strategies might be more or less feasible depending on the urban form and water
      demand. This paper aims to compare the environmental performance of implementing
      rainwater harvesting (RWH) systems in American and European cities. To do so, two
      neighborhoods with a water-stressed Mediterranean climate were selected in
      contrasting cities, i.e., Calafell (Catalonia, Spain) and Ukiah (California, US).
      Calafell is a high-density, tourist city, whereas Ukiah is a typical sprawled
      area. We studied the life cycle impacts of RWH in urban contexts by using runoff
      modeling before (i.e. business as usual) and after the implementation of this
      system. In general, cisterns were able to supply >75% of the rainwater demand for
      laundry and toilet flushing. The exception were multi-story buildings with roofs
      smaller than 200m2, where the catchment area was insufficient to meet demand. The
      implementation of RWH was environmentally beneficial with respect to the business
      as-usual scenario, especially because of reduced runoff treatment needs. Along
      with soil features, roof area and water demand were major parameters that
      affected this reduction. RWH systems are more attractive in Calafell, which had
      60% lower impacts than in Ukiah. Therefore, high-density areas can potentially
      benefit more from RWH than sprawled cities.

PMID- 29190571
TI  - Patterns and predictors of pain following lung transplantation.
AB  - OBJECTIVE: Our objective was to examine variability in pain levels following lung
      transplantation, and examine individual biopsychosocial factors influencing
      changes in pain. METHOD: We performed a retrospective study of a cohort of 150
      patients transplanted and discharged from Duke University Hospital between
      January 2015 and September 2016. During hospitalization and at clinic visits up
      to two months after discharge, subjective pain ratings were obtained using a 0-10
      Numeric Rating Scale. Psychiatric diagnoses of anxiety and depression and Center
      for Epidemiological Studies - Depression (CES-D) scores collected after hospital
      discharge were examined as predictors of post-surgery pain. Medical and surgical
      variables were examined as covariates. RESULTS: During hospitalization, pain
      ratings decreased over time (p<0.001). Predictors of higher pain levels included
      pre-transplant history of depression (p=0.001) and anxiety (p=0.04), bilateral
      lung transplant (p=0.03), and lower six-minute walk distance (p=0.02). Two months
      after discharge, 18% of patients reported continued pain and 34% remained on
      opioid pain medications. Two months after discharge, more frequent post-operative
      complications predicted higher pain levels in a univariate analysis (p=0.02)
      although this relationship was attenuated after adjustment for depression. In a
      multivariate analysis, elevated CES-D scores (p=0.002), and greater opioid use
      (p=0.031) predicted higher pain levels 2-months post-discharge. CONCLUSION: We
      conclude that patients with psychiatric comorbidities may be at risk for greater
      pain, and may require additional strategies for more effective pain management.

PMID- 29190569
TI  - The effect of the relative permittivity on the tactoid formation in nanoplatelet
      systems. A combined computer simulation, SAXS, and osmotic pressure study.
AB  - The structural properties, and the intracrystalline swelling of Na+-, and Ca2+
      montmorillonite (Na-, and Ca-mmt) have been investigated as an effect of
      decreasing the relative permittivity of the solvent, i.e. from water to ethanol
      (EtOH), utilizing the experimental techniques; small angle X-ray scattering
      (SAXS) and osmotic pressure measurements. The experimental data were compared
      with the continuum model, utilizing coarse-grained molecular dynamics bulk
      simulations, Monte Carlo simulations of two infinite parallel surfaces
      corresponding to two clay platelets, and the strong coupling theory. It was found
      that it is possible to tune the electrostatic interactions to obtain a transition
      from a repulsive to an attractive system for the Na-mmt by increasing the EtOH
      concentration, i.e. the Bjerrum length increases, and hence, the attractive ion
      ion correlation forces are enhanced. A qualitative agreement was observed between
      the simulations and the experimental results. Moreover, a non-monotonic behavior
      of the intracrystalline swelling of Ca-mmt as a function of EtOH concentration
      was captured experimentally, where an increase in the osmotic pressure, and
      hence, an increase in the d-spacing was found at low concentrations, indicating
      that repulsive short-ranged interactions dominate in the system. Theoretically,
      the non-monotonic behavior could not be captured with the continuum model,
      probably due to the limitation that the electrostatic interactions solely enters
      the Hamiltonian via the Bjerrum length.

PMID- 29190568
TI  - Polydopamine-assisted immobilization of hierarchical zinc oxide nanostructures on
      electrospun nanofibrous membrane for photocatalysis and antimicrobial activity.
AB  - Depositing of hierarchical ZnO nanostructures on electrospun nanofibers and their
      proper attachment has gained significant interest for myriad applications.
      However, the weak attachment of such nanostructures to the nanofiber surface
      limits their practical applications. In this study, a simple and efficient method
      has been developed for preparing hierarchical ZnO nanorod deposited polyurethane
      (PU) nanofiber by combining electrospinning, surface functionalization and
      hydrothermal treatment. Electrospun PU nanofibers were coated with polydopamine
      (Pdopa) via dip coating method. The resulting Pdopa coated PU nanofibrous mat was
      soaked in aqueous ZnO nanoparticles (ZnONPs) solution in order to seed the metal
      oxide particles on its surface. Later, ZnO nanorods (ZNRs) were grown on the ZnO
      seeded electrospun PU nanofiber via a hydrothermal process. X-ray photoelectron
      spectroscopy (XPS), Field-Emission Scanning electron microscopy (FE-SEM), X-ray
      diffraction pattern (XRD) and infra-red (IR) spectra indicated that ZnO nanorods
      firmly adhered to the functionalized PU nanofiber surface and had high
      photocatalytic/antimicrobial activity at the low-intensity UV-LED device with
      good reusability. The catechol group of Pdopa not only causes adhesion of ZnO
      nanostructures, but also act as an electron trap, preventing the recombination of
      e-h pairs and thereby improving the photocatalytic efficiency. We believe that
      the fabricated composite membrane with antifouling effect and photocatalytic
      activity is a potential candidate for organic pollutant degdration and wastewater
      purification.

PMID- 29190572
TI  - Increased prevalence and risk of anxiety disorders in adults with tinnitus: A
      population-based study in Taiwan.
AB  - OBJECTIVE: Tinnitus is a common disorder that may cause psychological distress
      and anxiety. The aim of this study was to investigate the association between
      anxiety disorders (ADs) and tinnitus in a large population. METHOD: We conducted
      a cross-sectional study using the National Health Insurance Research Database in
      Taiwan. Study subjects included 14,772 patients with tinnitus and 709,963 people
      in the general population who sought treatment in 2005. Distributions in ADs,
      age, sex, and medical comorbidities were compared between groups using chi
      squared tests. Multivariate logistic regression models adjusted for age, sex, and
      medical comorbidities were used to analyze the association between tinnitus and
      ADs. RESULTS: Prevalence of ADs in tinnitus and general population groups was
      3.9% and 1.5%, respectively, and this difference was significant (P<0.001).
      Diabetes mellitus, hypertension, hyperlipidemia, concussion or head injury,
      Meniere's disease, sensorineural hearing impairment, renal disease, coronary
      artery disease, and cerebrovascular disease were significantly more prevalent in
      the tinnitus group (all P-values<0.001). Multivariate logistic regression model
      demonstrated that patients with tinnitus were significantly associated with
      increased risk of ADs (adjusted OR=1.99; 95% CI=1.81-2.19; P<0.001). CONCLUSION:
      Because the risk of ADs was significantly higher in patients with tinnitus than
      in the general population, physicians should be aware of the importance of
      psychological factors in tinnitus management.

PMID- 29190574
TI  - A Case of cutaneous large B-cell lymphoma during treatment of multiple sclerosis
      with fingolimod.
AB  - The authors report a case of a 69-year-old woman with multiple sclerosis treated
      with fingolimod for duration of over one year who subsequently developed
      cutaneous large B cell lymphoma. There are few reported cases of lymphoma
      associated with fingolimod treatment for multiple sclerosis, but rates are higher
      than expected in the general population. The authors hope to promote awareness of
      the potential risk of this medication so that more diligent disease surveillance
      can be performed by both prescribing practitioners of fingolimod and their
      patients who receive it.

PMID- 29190576
TI  - The semiotics of medical image Segmentation.
AB  - As the interaction between clinicians and computational processes increases in
      complexity, more nuanced mechanisms are required to describe how their
      communication is mediated. Medical image segmentation in particular affords a
      large number of distinct loci for interaction which can act on a deep, knowledge
      driven level which complicates the naive interpretation of the computer as a
      symbol processing machine. Using the perspective of the computer as dialogue
      partner, we can motivate the semiotic understanding of medical image
      segmentation. Taking advantage of Peircean semiotic traditions and new
      philosophical inquiry into the structure and quality of metaphors, we can
      construct a unified framework for the interpretation of medical image
      segmentation as a sign exchange in which each sign acts as an interface metaphor.
      This allows for a notion of finite semiosis, described through a schematic
      medium, that can rigorously describe how clinicians and computers interpret the
      signs mediating their interaction. Altogether, this framework provides a unified
      approach to the understanding and development of medical image segmentation
      interfaces.

PMID- 29190579
TI  - Efficacy and safety of vigabatrin in Japanese patients with infantile spasms:
      Primary short-term study and extension study.
AB  - Vigabatrin was approved for the treatment of infantile spasms by the US Food and
      Drug Administration, but not in Japan at the time of initiating this clinical
      study because of concerns about irreversible peripheral visual field defects
      (VFDs). This study evaluated the efficacy and safety of vigabatrin for Japanese
      patients with infantile spasms. Of 15 patients (aged >=4weeks and <2years)
      enrolled, with the exception of two patients who did not receive vigabatrin, 13
      were treated with a titrated dosage of vigabatrin (50-150mg/kg/day; limited to
      3000mg/day). Twelve out of 13 patients receiving vigabatrin had spasms that were
      treatment refractory; these patients were concurrently treated with at least one
      other antiepileptic drug. One patient received vigabatrin monotherapy. Eight of
      the 13 patients (61.5% [95% CI: 31.6-86.1%]) had a >=50% reduction during the
      dose-adjustment phase compared with baseline in the frequency of spasms, with
      efficacy maintained through a 2-week maintenance phase. Spasms disappeared in six
      out of nine patients (66.7% [95% CI: 29.9-92.5%]) who transitioned to the
      maintenance phase and hypsarrhythmia on electroencephalography also resolved in
      four patients. Hypsarrhythmia was improved in another two patients. Six out of
      seven patients who continued treatment through Week 32 of an extension study
      reported ongoing efficacy for vigabatrin. The most common adverse events (AEs)
      were psychiatric disorders and nervous system disorders (n=8; 61.5%) that were
      generally mild in severity. No treatment-related peripheral VFDs were observed.
      No severe AEs or AEs resulting in discontinuation of vigabatrin therapy were
      reported. An abnormality in magnetic resonance images was observed in one patient
      during the extension period. Vigabatrin was deemed to be clinically effective and
      well tolerated in Japanese patients with infantile spasms.

PMID- 29190573
TI  - Common comorbidities and survival in MS: Risk for stroke, type 1 diabetes and
      infections.
AB  - BACKGROUND: Survival in MS has increased during the era of disease modifying
      therapies, but life expectancy in MS patients is still reduced by several years.
      Increased risk for common comorbidities related to brain health, such as risk for
      circulatory diseases have been reported in MS and could affect survival. In this
      paper, we studied age- and gender adjusted risks for circulatory diseases and
      related disorders, and their impact on overall MS survival in population of
      Southwest Finland. MATERIALS AND METHODS: The ICD-10 codes for hospital visits
      were searched from the administrative data pool from 1.1.2004 up to 31.12.2012
      for the resident MS and control cases at the Hospital District of Southwest
      Finland. The MS population under study consisted of prevalent cases in 1.1.2004
      and new cases from 1.1.2004 followed up to death or 31.12.2012. Patient documents
      were scrutinized to confirm the MS diagnosis (G 35) by the McDonald's criteria
      and to confirm the diagnoses and causes of death for the cerebro- and
      cardiovascular diagnoses under study. The randomly chosen 10-fold control
      population was matched by birth year and gender to calculate the coincident risks
      (odds ratio, OR) with 95% confidence intervals (95% CI) and another separate
      control population from the same patient pool was used to verify the stability of
      the results. P-values were calculated using Pearson's chi2 test. The Kaplan-
      Meier analysis log rank test was applied to study survival. RESULTS: During the
      follow-up 1074 confirmed MS cases were treated in the hospital district,
      including the deceased cases after 1.1.2004 (5.9%). The probability of survival
      was 82.4 years among MS and 85.6 years among the control cases, log rank p <
      0.001. The survival disadvantage within MS was associated with comorbidity for
      circulatory disease codes in ICD -10: I06-I71, log rank p < 0.001. The specific
      risk for ischemic and haemorrhagic stroke was significant with high OR of 1.49
      (95% CI 1.03- 2.35) and 2.5 (1.24-5.06) respectively. The two-fold risk for type
      1 diabetes in MS was significant, OR 2.1 (1.3-3.36). The main causes of death
      among the MS cases were infections and the coincident high risk for several
      infections was significant. There was no difference in the risk for acute
      myocardial infarct, transient ischemic attack, atrial fibrillation, hypertension,
      or obesity in comparison with the control cases. CONCLUSIONS: Given the high risk
      for stroke in this MS population and the observed complexity among the coincident
      common risk factors for circulatory diseases, the high risk for type 1 diabetes
      and common infections raise a need to recognize patients at risk with these
      conditions and with the other known risk factors such as metabolic syndrome and
      smoking. The survival disadvantage related to circulatory diseases observed in
      general population is true also in MS and should be recognized to reduce the
      burden of disease and premature mortality in MS.

PMID- 29190575
TI  - Dictionary-based fiber orientation estimation with improved spatial consistency.
AB  - Diffusion magnetic resonance imaging (dMRI) has enabled in vivo investigation of
      white matter tracts. Fiber orientation (FO) estimation is a key step in tract
      reconstruction and has been a popular research topic in dMRI analysis. In
      particular, the sparsity assumption has been used in conjunction with a
      dictionary-based framework to achieve reliable FO estimation with a reduced
      number of gradient directions. Because image noise can have a deleterious effect
      on the accuracy of FO estimation, previous works have incorporated spatial
      consistency of FOs in the dictionary-based framework to improve the estimation.
      However, because FOs are only indirectly determined from the mixture fractions of
      dictionary atoms and not modeled as variables in the objective function, these
      methods do not incorporate FO smoothness directly, and their ability to produce
      smooth FOs could be limited. In this work, we propose an improvement to Fiber
      Orientation Reconstruction using Neighborhood Information (FORNI), which we call
      FORNI+; this method estimates FOs in a dictionary-based framework where FO
      smoothness is better enforced than in FORNI alone. We describe an objective
      function that explicitly models the actual FOs and the mixture fractions of
      dictionary atoms. Specifically, it consists of data fidelity between the observed
      signals and the signals represented by the dictionary, pairwise FO dissimilarity
      that encourages FO smoothness, and weighted l1-norm terms that ensure the
      consistency between the actual FOs and the FO configuration suggested by the
      dictionary representation. The FOs and mixture fractions are then jointly
      estimated by minimizing the objective function using an iterative alternating
      optimization strategy. FORNI+ was evaluated on a simulation phantom, a physical
      phantom, and real brain dMRI data. In particular, in the real brain dMRI
      experiment, we have qualitatively and quantitatively evaluated the
      reproducibility of the proposed method. Results demonstrate that FORNI+ produces
      FOs with better quality compared with competing methods.

PMID- 29190577
TI  - CTAB and SDS assisted facile fabrication of SnO2 nanoparticles for effective
      degradation of carbamazepine from aqueous phase: A systematic and comparative
      study of their degradation performance.
AB  - In the present study, SnO2 nanoparticles were successfully synthesized by
      chemical precipitation method using anhydrous aspartic acid and surfactant at two
      annealing temperatures, 300  degrees C and 600  degrees C. The effect of
      surfactants cationic CTAB and anionic SDS on the synthesized SnO2 nanoparticles
      (NPs) were studied elaborately. In this article, for the first time, SnO2 NPs
      were employed as an excellent photocatalyst in the degradation of carbamazepine
      (CBZ), a popular antiepileptic drug which is most commonly detected
      pharmaceutically active compounds (PhACs) in municipal wastewater under UV-C
      light irradiation. Comparative studies between the photocatalytic activity of
      SnO2 NPs synthesized with CTAB (SC1) and SDS (SS1) on the degradation of the CBZ
      drug were investigated. Parameters like the effect of catalytic loading, initial
      concentration, pH and contact time were also studied for optimization. The
      results indicate that SC1 is a better photocatalyst with rate constant 6.66 * 10
      2 min-1 than SS1 with rate 5.7 * 10-2 min-1. To determine the transformation
      product formed on the photodegradation LCMS (ESI) analysis was done. The
      synthesized SnO2 NPs can be recycled up to 8th cycles without any notable
      alteration in its photocatalytic activity.

PMID- 29190581
TI  - Melamine-containing polyphosphazene wrapped ammonium polyphosphate: A novel
      multifunctional organic-inorganic hybrid flame retardant.
AB  - To achieve superior fire safety epoxy resins (EP), a novel multifunctional
      organic-inorganic hybrid, melamine-containing polyphosphazene wrapped ammonium
      polyphosphate (PZMA@APP) with rich amino groups was prepared and used as an
      efficient flame retardant. Thanks to the cross-linked polyphosphazene part,
      PZMA@APP exhibited high flame retardant efficiency and smoke suppression to the
      EP composites. Thermogravimetric analysis indicated that PZMA@APP significantly
      enhanced the thermal stability of EP composites. The obtained sample passed UL-94
      V-0 rating with 10.0wt% addition of PZMA@APP. Notably, inclusion of incorporating
      PZMA@APP leads to significantly decrease on fire hazards of EP, for instance,
      bring about a 75.6% maximum decrease in peak heat release rate and 65.9% maximum
      reduction in total heat release, accompanied with lower smoke production rate and
      higher graphitized char layer. With regards to mechanical property, the glass
      transition temperature of EP/PZMA@APP10.0 was as high as 184.5 degrees C. In
      particular, the addition of PZMA@APP did not worsen the mechanical properties,
      compared to pure APP. It was confirmed that the participation of melamine
      containing polyphosphazene could significantly enhance the quality of char layer
      and thereby resulting the higher flame retardant efficiency of PZMA@APP.

PMID- 29190582
TI  - Superhydrophobic and superoleophilic porous reduced graphene oxide/polycarbonate
      monoliths for high-efficiency oil/water separation.
AB  - Superhydrophobic and superoleophilic porous reduced graphene oxide/polycarbonate
      (RGO/PC) monoliths with novel micro-nanoscale binary structure were first
      fabricated by thermally impacted nonsolvent induced phase separation (TINIPS)
      method. Owing to the unique pore structure, the porous monoliths possessed high
      specific surface area (137.19m2/g) and porosity (91.3%). The superhydrophobic
      RGO/PC monoliths exhibited excellent capability to selectively adsorb a wide
      range of oils and organic solvents from water. Furthermore, the monoliths could
      keep a stable repellency against corrosive mediums (e.g., acidic and alkali
      solutions). Based on these superior properties, porous RGO/PC monoliths will be a
      promising candidate for high-efficiency oil/water separation to deal with water
      pollution.

PMID- 29190578
TI  - Evaluation of a full-scale wastewater treatment plant upgraded with ozonation and
      biological post-treatments: Abatement of micropollutants, formation of
      transformation products and oxidation by-products.
AB  - To protect the ecosystem and drinking water resources in Switzerland and in the
      countries of the downstream catchments, a new Swiss water protection act entered
      into force in 2016 aiming to reduce the discharge of micropollutants from
      wastewater treatment plants (WWTPs). As a consequence, selected WWTPs must be
      upgraded by an advanced treatment for micropollutant abatement with suitable and
      economic options such as (powdered) activated carbon treatment or ozonation. WWTP
      Neugut (105'000 people equivalent) was the first WWTP in Switzerland to implement
      a long-term full-scale ozonation. Differing specific ozone doses in the range of
      0.35-0.97 g O3/g DOC were applied to determine the adequate ozone dose to fulfill
      the requirements of the Swiss water protection act. Based on this assessment, a
      specific ozone dose of 0.55 g O3/g DOC is recommended at this plant to ensure an
      average abatement of the twelve selected indicator substances by >=80% over the
      whole treatment. A monitoring of 550 substances confirmed that this dose was very
      efficient to abate a broad range of micropollutants by >79% on average. After
      ozonation, an additional biological post-treatment is required to eliminate
      possible negative ecotoxicological effects generated during ozonation caused by
      biodegradable ozonation transformation products (OTPs) and oxidation by-products
      (OBPs). Three biological treatments (sand filtration, moving bed, fixed bed) and
      granular activated carbon (GAC, fresh and pre-loaded) filtration were evaluated
      as post-treatments after ozonation. In parallel, a fresh GAC filter directly
      connected to the effluent of the secondary clarifier was assessed. Among the
      three purely biological post-treatments, the sand filtration performed best in
      terms of removal of dissolved organic carbon (DOC), assimilable organic carbon
      (AOC) and total suspended solids (TSS). The fresh activated carbon filtration
      ensured a significant additional micropollutants abatement after ozonation due to
      sorption. The relative abatement of the indicator substances ranged between 20
      and 89% after 27'000 bed volumes (BV) and was still substantial at 50'000 BV. In
      an identical GAC filter running in parallel and being fed with the effluent of
      the secondary clarifier, the elimination was less efficient. Seven primary OTPs
      (chlorothiazide and six N-oxides) formed during ozonation could be quantified
      thanks to available reference standards. Their concentration decreased with
      increasing specific ozone doses with the concomitant formation of other OTPs. The
      seven OTPs were found to be stable compounds and were not abated in the
      biological post-treatments. They were sorbed in the fresh GAC filter, but less
      efficiently than the corresponding parent compounds. Two OBPs, bromate (BrO3-)
      and N-nitrosodimethylamine (NDMA), were formed during ozonation but did not
      exceeded 5 MUg/L for bromate and 30 ng/L for NDMA at the recommended specific
      ozone dose of 0.55 g O3/g DOC. NDMA was well abated in all post-treatments
      (minimum 41% during fixed bed filtration, maximum 83% during fresh GAC
      filtration), while bromate was very stable as expected.

PMID- 29190583
TI  - Synthesis of CuCl/Boehmite adsorbents that exhibit high CO selectivity in CO/CO2
      separation.
AB  - We developed nanoporous adsorbent exhibiting unprecedented performance in
      separation of toxic carbon monoxide (CO). The adsorbent was prepared by
      dispersing CuCl on mesoporous boehmite via thermal monolayer dispersion route. A
      key point of the present synthesis is dispersing optimized amount of CuCl on the
      boehmite at a moderate temperature to maintain the characteristics of the
      boehmite. We performed a systematic study to reveal that a CuCl/boehmite
      composite (30wt% CuCl in total) thermally treated at 573K was the best optimized
      sample for CO separation. The CuCl/boehmite had a high capacity of CO adsorption
      (1.56mmolg-1) and an exceedingly low capacity of CO2 adsorption (0.13mmolg-1)
      under 100kPa of each gas at 293K. The CO/CO2 separation factor was 12.4. To the
      best of our knowledge, this value is the best on record. The achievement of this
      work is attributed to finding a new type of suitable supporting material:
      boehmite. The boehmite has a high affinity to CuCl, exhibits excellent dispersion
      of the CuCl, and achieves a superior CO adsorption capacity. However, it has a
      weak interaction with CO2. The CuCl/boehmite composite is a promising adsorbent
      for selective separation of CO from combustion exhaust and industrial off-gas
      streams.

PMID- 29190587
TI  - A multipronged QSAR approach to predict algal low-toxic-effect concentrations of
      substituted phenols and anilines.
AB  - Environmental risk assessment procedures require acute and chronic toxicity
      values of hazardous chemicals. In this respect, the 96-h toxicity bioassays of
      nitro-, methyl-, methoxy-, chloro-, and nitrile- substituted phenols and anilines
      to Chlorella vulgaris were performed. Median inhibitory and low-toxic-effect
      concentrations were reported. Significant correlations between acute and chronic
      toxicities were found for the chemicals in the data set regardless of mode of
      action. Consequently, linear models employing theoretical and empirical
      descriptors were developed for the prediction of NOEC and IC20. The outcome of
      the study will be beneficial in the risk assessments of organic chemicals and
      setting water quality standards by the regulators.

PMID- 29190580
TI  - Potentially antidiabetic and antihypertensive compounds identified from Pistacia
      atlantica leaf extracts by LC fingerprinting.
AB  - The objective of this paper is to evaluate the variations in the ability of
      Pistacia atlantica leaves to inhibit enzymes linked to type 2 diabetes (alpha
      amylase and alpha-glucosidase) and to hypertension (angiotensin converting enzyme
      I (ACE-I)), depending on harvesting month, gender and growing region, as well as
      to identify the peaks in chromatographic fingerprints that potentially correspond
      to components with enzymatic inhibitory activities. In this study, LC
      fingerprints of P. atlantica leave extracts were developed. Peaks which were
      probably responsible for the anti-amylase, anti-glucosidase and anti-ACE-I
      activities were assigned. For the latter purpose, the relevant information was
      extracted, linking the chromatographic fingerprints with the activities using a
      linear multivariate calibration technique, i.e., Partial Least Squares (PLS)
      regression. Prior to the construction of the models, the fingerprints are aligned
      using a warping method, called Correlation Optimized Warping (COW). Besides COW,
      different other data pretreatment methods were applied and compared. Our findings
      revealed that the influence of the growing region and gender on the alpha
      amylase, alpha-glucosidase and ACE-I inhibitory activities of P. atlantica leaves
      was less important than the harvest time. Thirteen common peaks were selected
      from the chromatograms and used as a dataset to model the biological activities.
      The peaks potentially responsible for the biological activity of the samples were
      indicated by studying the regression coefficients of the models. Seven peaks
      corresponding to possibly anti-amylase compounds were found, while 6 peaks were
      considered important for inhibiting the alpha-glucosidase activity. Furthermore,
      the regression coefficients of the hypertension model indicated eight peaks as
      being important for inhibiting the ACE-I activity. The contributions of
      individual phenolic compounds of P. atlantica leaves to the alpha-amylase, alpha
      glucosidase and ACE-I inhibitory activities were also identified. This
      investigation showed that the extract of P. atlantica leaves provides a rational
      basis for the isolation and development of antidiabetic and antihypertensive
      agents.

PMID- 29190584
TI  - Fabrication of RuO2-Ag3PO4 heterostructure nanocomposites: Investigations of band
      alignment on the enhanced visible light photocatalytic activity.
AB  - The RuO2-Ag3PO4 heterostructured nanocomposite was successfully synthesized by
      facile in situ deposition of porous ruthenium oxide (RuO2) nanoparticles on the
      surface of the silver phosphate (Ag3PO4). Under visible light irradiation, the
      0.5wt.% RuO2-Ag3PO4 heterostructure photocatalyst exhibits enhanced
      photocatalytic efficiency compared to other composites of RuO2-Ag3PO4 and Ag3PO4.
      The optimized 0.5wt.% RuO2-Ag3PO4 nanocomposites exhibited 1.5 times enhanced
      photocatalytic activity towards the degradation of methylene blue (MB) than
      Ag3PO4. Moreover, the degradation rate of 0.5wt.% RuO2-Ag3PO4 nanocomposite
      towards the cationic dyes MB and rhodamine B (RhB) was nearly 6.6 times and 4.7
      times higher than that towards the anionic dye methyl orange (MO). The formed
      heterojunction electric field of 310mV at the interface between RuO2 and Ag3PO4
      heterostructure induces downward band bending of Ag3PO4. Also, this electric
      field increases the separation efficiency of electrons-holes resulting higher
      degradation efficiency. The quenching effect of scavengers test confirms that
      holes are reactive species and the RuO2-Ag3PO4 nanocomposite is highly stable,
      exhibited 88% of MB degradation after 4 recycles. The RuO2-Ag3PO4 nanocomposites
      inhibit self oxidation of Ag3PO4 resulting improved efficiency and stability.

PMID- 29190585
TI  - A novel "turn-on" fluorescent probe based on triphenylimidazole-hemicyanine dyad
      for colorimetric detection of CN- in 100% aqueous solution.
AB  - A new colorimetric fluorescent probe (MCy) for CN- is designed and synthesized
      based on triphenylimidazole-hemicyanine dyad. The probe shows high selectivity
      towards CN- in 100% aqueous solution even in the presence of other competitive
      anions such as F-, Cl-, AcO-, NO2-, H2PO4-, I-, SCN-, SO42-, NO3-, HCO3-, Br- and
      S2-. Upon nucleophilic addition of CN- to the indolium group, the probe displays
      large blue-shift in UV-vis spectrum and remarkable "turn-on" fluorescence owing
      to the disruption of intramolecular charge transfer. Meanwhile, the probe also
      undergoes a naked-eye discernible color change from orange to light pink in the
      sunlight as well as an obvious fluorescence color change from non-emissive to
      bright blue under a UV lamp. The detection limit of CN- in aqueous solution can
      be as low as 20.6nM, which is much lower than the permissible level of CN- in
      drinking water according to the WHO. In addition, the probe has been successfully
      used to determine CN- in real water samples as well as to fabricate test paper
      kit for CN- detection.

PMID- 29190586
TI  - Efficiency of the formulated plant-growth promoting Pseudomonas fluorescens MC46
      inoculant on triclocarban treatment in soil and its effect on Vigna radiata
      growth and soil enzyme activities.
AB  - For bioaugmentation-based treatment of triclocarban (TCC), an emerging soil
      pollutant that is recalcitrant to biodegradation and phytotransformation,
      efficient TCC-degrading bacteria with an effective soil-delivering means are
      required. This work developed the formulated bacterial inoculant, and
      successfully demonstrated its TCC removal and detoxification performance in pot
      soil experiment with Vigna radiata plants. The soil bacterium Pseudomonas
      fluorescens MC46 was isolated as TCC-degrading, plant-growth promoting bacterium.
      The characterizations were conducted in vitro revealing that it could utilize TCC
      as a sole carbon source, and at a wide and higher concentration range from 1.6
      31.6mgkg-1 than those previously reported, while the detoxification was assessed
      by cytogenotoxicity and phytotoxicity tests. The developed sawdust-based
      inoculant formula combined with molasses (5% w/w), and either PEG or CMC-starch
      blend (1% w/w) could maintain a 20-week shelf-life inoculant stability in terms
      of cell viability, and TCC-degrading activity. Bioaugmentation of the formulated
      inoculants into TCC-contaminated soil efficiently removed TCC up to 74-76% of the
      initial concentration, mitigated toxicity, restored plant growth and health, and
      enhanced soil enzyme activities. This work is the first to demonstrate potential
      application of the formulated plant-growth promoting bacterial inoculant for the
      treatment and detoxification of a persistent TCC contaminated in soil.

PMID- 29190590
TI  - The impact of simulation based education on nursing confidence, knowledge and
      patient outcomes on general medicine units.
AB  - The ability to quickly and reliably detect a clinically deteriorating patient and
      intervene appropriately is a skill nurses are expected to bring into practice.
      Simulation education has been shown to improve nurses' knowledge, confidence and
      communication, especially when focused on deteriorating patients. In a simulation
      center at a large tertiary level Canadian teaching hospital, a 4 h simulation
      based education session was developed for general medicine nursing staff. The
      education included a didactic lecture followed by four 40 min simulation
      scenarios focused on deteriorating patient. This study was designed as a pre- and
      post-analytic design. It utilized a paper based survey completed at three
      separate time points to measure confidence and knowledge. The study also examined
      data from the Critical Care Outreach nurse audits and site code blue audit data.
      Results demonstrated statistically significant improvements in nursing confidence
      and knowledge, and were sustained over the three month follow-up period.

PMID- 29190588
TI  - LRFN (leucine-rich repeat and fibronectin type-III domain-containing protein)
      recognizes bacteria and promotes hemocytic phagocytosis in the Pacific oyster
      Crassostrea gigas.
AB  - In bivalve mollusks, circulating hemocyte mediated phagocytosis is one of the
      primary ways to eliminate invading microbes. Here, we have identified one CgLRFN
      (leucine-rich repeat and fibronectin type-III domain-containing protein) in the
      Crassostrea gigas as a novel transmembrane LRR (Leucine-rich repeat) domain
      containing protein in C. gigas, homologous to the jawless fish VLR protein, that
      plays an important role in recognizing bacteria and promoting hemocytic
      phagocytosis. Tissue distribution analysis of CgLRFN in Pacific oyster showed
      that it is widely expressed in various tissues like the gills, adductor muscles,
      digestive glands, gonads, heart and in the hemocytes. Furthermore, infection of
      Pacific oysters with two marine Vibrio strains V. alginolyticus and V.
      parahaemolyticus was found to significantly increase CgLRFN expression in the
      hemocytes. Analysis of subcellular localization showed that CgLRFN is primarily
      localized in the cell membrane. Additionally, CgLRFN was found to be able to bind
      both the bacterial strains, indicating its possible role as a cell surface
      receptor. Flow cytometry analysis revealed that CgLRFN coated bacteria was
      phagocytosed by oyster hemocytes at a significantly higher rate compared to the
      uncoated bacteria. Finally, RNAi mediated knockdown of CgLRFN in vivo resulted in
      reduced clearance of both the bacterial strains from the oyster hemolymph.
      Overall, our study demonstrates that CgLRFN acts as a pattern recognition
      receptor for Vibrio spp. and promotes hemocytic phagocytosis in the Pacific
      oyster, which is critical for understanding the mechanism of bacterial infection
      in lower invertebrates, and also contributes to disease management of this
      economically and ecologically important marine mollusk.

PMID- 29190592
TI  - Performance of direct anaerobic digestion of dewatered sludge in long-term
      operation.
AB  - Direct anaerobic digestion of dewatered sludge with total solids (TS) content of
      15-20% was tested in a horizontal digester for one and half years. The system
      kept stable with pH 7-8. The concentration of volatile fatty acids was lower than
      800 mg/L, free ammonia nitrogen was lower than 200 mg/L, and total alkalinity
      kept higher than 6000 mg/L. The performance was influenced by organic load rate
      (OLR) and organic content in feed sludge. When volatile solids (VS) in TS of feed
      sludge reached 60-65% at OLR 3.50-3.70 g/(L.d), the process exhibited the best
      performance with organic removal rate of 32.19 +/- 7.73% and methane production
      of 156.86 +/- 13.05 ml/g VS added. Microbial analyses indicated that
      Methanosarcina became predominant and Methanosaeta almost disappeared. Moreover,
      hydrogenotrophic and methylotrophic methanogens accounted for 18.13-29.40% and
      11.58-29.56% of the total, respectively. These provide a new guideline for small
      scale or centralized sludge treatment.

PMID- 29190591
TI  - First report of a fish kill episode caused by pyrethroids in Italian freshwater.
AB  - INTRODUCTION: Fish kills are events of strong emotional impact on the population
      because of the frequent suspicion that they can be the result of serious
      pollution accidents. As a matter of fact, they are often due to natural
      occurrences, such as low levels of dissolved oxygen in the water, but in many
      cases the causes remain unknown. Fish are particularly sensitive to pesticides
      and pyrethroids are reported to be the most ecotoxicologically active in the
      aquatic environment. Nevertheless, the reported cases of massive wild fish
      mortalities due to these toxicants are very few. This paper describes a fish kill
      episode occurred in the Padua Province (Veneto Region - North Eastern Italy)
      which involved several fish species and for which it was possible to identify the
      cause in the presence of pyrethroids in the water. CASE PRESENTATION: When a
      whitish liquid coming from the rainwater drain of an industrial area was seen to
      be spilling into a drainage channel, a fish massive mortality was noticed and
      investigated. The collected water samples showed the presence of relevant
      concentrations of cypermethrin, permethrin, deltamethrin and tetramethrin.
      Analyses on the fish tissues revealed the presence of cypermethrin and permethrin
      at a concentration range of 476-2834MUg/kg and 346-2826MUg/kg on a lipid basis,
      respectively. DISCUSSION: According to the results of the performed analyses, we
      can reasonably state that the described episode had been caused by the exposure
      of biota to high concentrations of pyrethroids. The present case report
      significantly contributes to the limited literature available on pesticides
      related fish kills. Moreover, it highlights the importance of sharing protocols
      for fish kill management at a national level, as this would help to better define
      the roles of the different institutions involved and to improve the investigation
      and the reporting of these events.

PMID- 29190589
TI  - Professional formation through personal involvement and value integration.
AB  - Formation is an important part of nursing education, and it is the responsibility
      of nurse educators to facilitate learning situations that provide students with
      opportunities for personal discovery. Studies have shown that awareness of one's
      own vulnerability can be a source of professional maturation and courageous
      action. The study setting is a Christian university that emphasises its value
      base through the perspective of diakonia in the nursing programme. Diakonia is
      understood as the provision of caring. Two hundred and forty-five pages of
      reflective journals from 124 third-year students were analysed with qualitative
      content analysis. The main theme of the study was Professional formation through
      personal involvement and value integration. Four categories emerged: 1) Diakonia
      as a guide to professional compassion; 2) Consciousness of one's own values; 3)
      The urge to act courageously; and 4) Choosing to spend the time available. The
      article discusses how students can integrate values in their professional lives
      by using all senses when learning in real-life situations and by using systematic
      reflection alone and together with others. Professional formation is an ongoing
      process, and we have found that mandatory participation, reiteration and
      progression are important conditions for such formation to occur.

PMID- 29190593
TI  - Co-production of bio-ethanol, xylonic acid and slow-release nitrogen fertilizer
      from low-cost straw pulping solid residue.
AB  - A novel bio-refinery sequence yielding varieties of co-products was developed
      using straw pulping solid residue. This process utilizes neutral sulfite
      pretreatment which under optimal conditions (160  degrees C and 3% (w/v) sulfite
      charge) provides 64.3% delignification while retaining 90% of cellulose and 67.3%
      of xylan. The pretreated solids exhibited excellent enzymatic digestibility, with
      saccharification yields of 86.9% and 81.1% for cellulose and xylan, respectively.
      After pretreatment, the process of semi-simultaneous saccharification and
      fermentation (S-SSF) and bio-catalysis was investigated. The results revealed
      that decreased ethanol yields were achieved when solid loading increased from 5%
      to 30%. An acceptable ethanol yield of 76.8% was obtained at 20% solid loading.
      After fermentation, bio-catalysis of xylose remaining in fermentation broth
      resulted in near 100% xylonic acid (XA) yield at varied solid loadings. To
      complete the co-product portfolio, oxidation ammoniation of the dissolved lignin
      successfully transformed it into biodegradable slow-release nitrogen fertilizer
      with excellent agricultural properties.

PMID- 29190598
TI  - Evaluation and Management of Kidney Calculi.
AB  - INTRODUCTION: The recent change in the view towards nephrolithiasis from a benign
      isolated disease to a disorder associated with numerous systemic and chronic
      conditions has added to the importance of a more thorough and timely diagnostic
      and therapeutic intervention. MATERIALS AND METHODS: Both original and review
      articles found via the PubMed search on recent evaluation and management
      strategies of urinary calculi were reviewed. These resources were integrated with
      the authors' knowledge of the field. RESULTS: The emerging evidence attests to
      the association of nephrolithiasis with many morbid and fatal diseases, such as
      coronary heart disease, ischemic stroke, hypertension, chronic kidney
      insufficiency, malignancies, and bone loss, as well as the economic burden of
      urinary calculus on health system and work force. CONCLUSIONS: Findings of this
      review justify a timely and comprehensive workup and dietary-therapeutic measures
      in order to prevent, treat, and control the associated complications of this
      condition.

PMID- 29190597
TI  - Insecticidal activity of camphene, zerumbone and alpha-humulene from Cheilocostus
      speciosus rhizome essential oil against the Old-World bollworm, Helicoverpa
      armigera.
AB  - The fast-growing resistance development to several synthetic and microbial
      insecticides currently marketed highlighted the pressing need to develop novel
      and eco-friendly pesticides. Among the latter, botanical ones are attracting high
      research interest due to their multiple mechanisms of action and reduced toxicity
      on non-target vertebrates. Helicoverpa armigera (Lepidoptera: Noctuidae) is a key
      polyphagous insect pest showing insecticide resistance to several synthetic
      molecules used for its control. Therefore, here we focused on the rhizome
      essential oil extracted from an overlooked Asian plant species, Cheilocostus
      speciosus (J. Konig) C. Specht (Costaceae), as a source of compounds showing
      ingestion toxicity against H. armigera third instar larvae, as well as ovicidal
      toxicity. In acute larvicidal assays conducted after 24h, the C. speciosus
      essential oil achieved a LC50 value of 207.45ug/ml. GC and GC-MS analyses
      highlighted the presence of zerumbone (38.6%), alpha-humulene (14.5%) and
      camphene (9.3%) as the major compounds of the oil. Ingestion toxicity tests
      carried out testing these pure molecules showed LC50 values of 10.64, 17.16 and
      20.86ug/ml, for camphene, zerumbone and alpha-humulene, respectively. Moreover,
      EC50 values calculated on H. armigera eggs were 35.39, 59.51 and 77.10ug/ml for
      camphene, zerumbone and alpha-humulene, respectively. Overall, this study
      represents the first report on the toxicity of C. speciosus essential oil against
      insect pests of agricultural and medical veterinary importance, highlighting that
      camphene, zerumbone and alpha-humulene have a promising potential as eco-friendly
      botanical insecticides.

PMID- 29190594
TI  - Correlating microbial community structure with operational conditions in
      biological aerated filter reactor for efficient nitrogen removal of municipal
      wastewater.
AB  - In this study, the combination of strengthen circulation anaerobic (SCA) and
      biological aerated filter (BAF) reactor was employed to treat municipal
      wastewater. Different reflux percentages or gas/water ratios were selected for
      evaluating the removal performance of contaminants in SCA-BAF system and
      sequential nitrification and denitrification process in BAF reactor. In general,
      reflux percentage (200%) and gas/water ratio (3:1) were a relatively suitable
      operational condition for BAF reactor. The COD, NH3-N, TN concentrations of
      effluents collected from BAF reactor varied in the ranges of 18-80, 0.2-7.2, 9.1
      33.0 mg L-1, respectively. A higher NO3-N concentration in effluents of BAF
      reactor resulted from the lack of organic carbon resource in wastewater. High
      throughput sequencing analysis indicated that different nitrification and
      denitrification bacteria thrived in the BAF reactor. The DO, NO2-N and NO3-N
      concentrations showed a strong correlation with Nitrospira and Nitrosomonas in
      bacterial samples outlet (c and e) under gas/water ratio of 3:1.

PMID- 29190599
TI  - Irreversible Lesions of Tacrolimus-induced Posterior Reversible
      Leukoencephalopathy Syndrome.

PMID- 29190600
TI  - Hyaluronic Acid as a New Biomarker to Differentiate Acute Kidney Injury From
      Chronic Kidney Disease.
AB  - INTRODUCTION: It may be difficult to differentiate acute kidney injury from
      chronic kidney disease in patients with no past medical reports of kidney
      function. This study aimed to investigate the role of serum hyaluronic acid (HA),
      which is known as a marker of fibrosis, in differential diagnosis of kidney
      failure. MATERIALS AND METHODS: A total of 90 patients (52 women and 38 mne)
      admitted to our renal unit with uremia for the first time were included. Serum HA
      level was measured. The diagnostic role of the test was investigated using the
      receiver operator curve curves. RESULTS: The mean age of the patients was 54.6 +/
      17.9 years. The diagnosis was chronic kidney disease (CKD) in 41.1%, acute kidney
      injury (AKI) in 48.9%, AKI on CKD in 6.7% (3 died without a diagnosis). The mean
      serum HA was significantly higher in the CKD group (146.1 +/- 119.3 ng/mL) than
      the AKI group (68.9 +/- 69.1 ng/mL; P < .001). Serum HA significantly correlated
      with proteinuria (r = 0.717, P < .001) and serum albumin level (r = - 0.599, P <
      .001) in the CKD group only. Serum HA cutoff level of 61 ng/dL had a sensitivity
      of 82% and specificity of 67% for differential diagnosis of AKI and CKD.
      CONCLUSIONS: Serum HA level may be used as tool to differentiate AKI from CKD.
      Further larger studies are warranted to clarify the definite the role of this
      marker.

PMID- 29190596
TI  - The impacts of modern-use pesticides on shrimp aquaculture: An assessment for
      north eastern Australia.
AB  - The use of pyrethroid and neonicotinoid insecticides has increased in Australia
      over the last decade, and as a consequence, increased concentrations of the
      neonicotinoid insecticide imidacloprid have been measured in Australian rivers.
      Previous studies have shown that non-target crustaceans, including commercially
      important species, can be extremely sensitive to these pesticides. Most shrimp
      farms in Australia are predominantly located adjacent to estuaries so they can
      obtain their required saline water, which support multiple land uses upstream
      (e.g. sugar-cane farming, banana farming, beef cattle and urbanisation). Larval
      and post-larval shrimp may be most susceptible to the impacts of these pesticides
      because of their high surface area to volume ratio and rapid growth requirements.
      However, given the uncertainties in the levels of insecticides in farm intake
      water and regarding the impacts of insecticide exposure on shrimp larvae, the
      risks that the increased use of new classes of pesticide pose towards survival of
      post-larval phase shrimp cannot be adequately predicted. To assess the potential
      for risk, toxicity in 20day past hatch post-larval Black Tiger shrimp (Penaeus
      monodon) to modern use insecticides, imidacloprid, bifenthin, and fipronil was
      measured as decreased survival and feeding inhibition. Post-larval phase shrimp
      were sensitive to fipronil, bifenthrin, and imidacloprid, in that order, at
      concentrations that were comparable to those that cause mortality other
      crustaceans. Bifenthrin and imidacloprid exposure reduced the ability of post
      larval shrimp to capture live prey at environmentally realistic concentrations.
      Concentrations of a broad suite of pesticides were also measured in shrimp farm
      intake waters. Some pesticides were detected in every sample. Most of the
      pesticides detected were measured below concentrations that are toxic to post
      larval shrimp as used in this study, although pesticides exceed guideline values,
      suggesting the possibility of indirect or mixture-related impacts. However, at
      two study sites, the concentrations of insecticides were sufficient to cause
      toxicity in shrimp post larvae, based on the risk assessment undertaken in this
      study.

PMID- 29190595
TI  - Chronic exposure to a glyphosate-containing pesticide leads to mitochondrial
      dysfunction and increased reactive oxygen species production in Caenorhabditis
      elegans.
AB  - Glyphosate-containing herbicides are among the most widely-used in the world.
      Although glyphosate itself is relatively non-toxic, growing evidence suggests
      that commercial herbicide formulations may lead to increased oxidative stress and
      mitochondrial inhibition. In order to assess these mechanisms in vivo, we
      chronically (24h) exposed Caenorhabditis elegans to various concentrations of the
      glyphosate-containing herbicide TouchDown (TD). Following TD exposure, we
      evaluated the function of specific mitochondrial electron transport chain
      complexes. Initial oxygen consumption studies demonstrated inhibition in mid- and
      high-TD concentration treatment groups compared to controls. Results from
      tetramethylrhodamine ethyl ester and ATP assays indicated reductions in the
      proton gradient and ATP levels, respectively. Additional studies were designed to
      determine whether TD exposure resulted in increased reactive oxygen species (ROS)
      production. Data from hydrogen peroxide, but not superoxide or hydroxyl radical,
      assays showed statistically significant increases in this specific ROS. Taken
      together, these data indicate that exposure of Caenorhabditis elegans to TD leads
      to mitochondrial inhibition and hydrogen peroxide production.

PMID- 29190610
TI  - Next-Generation Sequencing in Diagnostics and Clinical Research.

PMID- 29190601
TI  - Cytokine Gene Polymorphism in Children With Idiopathic Nephrotic Syndrome.
AB  - INTRODUCTION: Idiopathic nephrotic syndrome (INS) is a glomerular disease with
      completely unclear pathogenesis and different responses to steroid therapy. This
      study aimed to investigate the role of cytokine genes promoter polymorphisms in
      steroid therapy responses. MATERIALS AND METHODS: One hundred children with INS
      and 30 healthy controls were studied. Genotyping of TNF-alpha-G308A single
      nucleotide polymorphism was done using polymerase chain reaction-restriction
      fragment length polymorphism method, while of IL-6-G174C single nucleotide
      polymorphism was done using real-time polymerase chain reaction. RESULTS: The IL
      6-G174C exhibited a significantly different genotype distribution among the
      children with INS compared with the controls (GG versus CC, P = .02; GG versus
      GC, P = .003; odds ratio [OR], 5.83; 95% confidence interval [CI], 1.64 to 20.70;
      as well as alleles distribution of G versus C, P ? .001; OR, 7.57; 95% CI, 2.28
      to 25.17). With regard to TNF-alpha-G308A genotype, there was no significant
      difference in genotype distribution of the children with INS compared with the
      controls, but a significant difference was observed at the alleles level.
      Comparing the steroid-resistant group with the steroid-sensitive group,
      significant association was found at genotypic level in case of IL-6-G174C (GG
      versus CC, P = .03; OR, 5.52; 95% CI, 1.39 to 21.89), but no association was
      found regarding GG versus GC. At the allelic level of IL-6-G174C, there was no
      significant association either. CONCLUSIONS: IL-6-G174C and TNFalpha-G308A
      polymorphisms may affect susceptibility to idiopathic nephrotic syndrome and
      might affect steroid response in INS patients.

PMID- 29190602
TI  - Protective Effects of Pomegranate Juice on Nephrotoxicity Induced by Captopril
      and Gentamicin in Rats.
AB  - INTRODUCTION: Nephrotoxicity is an important side effects of captopril and
      gentamicin. This study investigated the prophylactic and protective effects of
      pomegranate juice (PJ) on the kidney exposed to nephrotoxicity induced by these
      medications. MATERIALS AND METHODS: Wistar male rats received drinking water
      (groups 1 to 3) or PJ at doses of 4 mL/kg (group 4), 10 mL/kg (groups 5 and 7),
      and 15 mL/kg (group 6) for 14 days. Captopril and gentamicin were administrated
      on days 10 and 14 to groups 1 and 2, respectively, while groups 3 to 6 received
      both. Group 7 did not receive anything. The serum, urine, and renal tissue
      parameters were measured after the experiment. RESULTS: Group 1 (captopril) had a
      higher malondialdehyde level than groups 4, 5, 6, and 7 with PJ (P <0.05), and
      group 3 (captopril and gentamicin) showed the most significant malondialdehyde
      level compared to other groups (P < .001). Group 5 (captopril, gentamicin, and
      PJ, 10 mL/kg) had the most significant sodium excretion compared to other groups
      (P < .001), and group 2 (gentamicin) showed the highest potassium absolute
      excretion (P < .001). The instability of the renal index was observed during the
      experiment for the groups receiving drinking water, while no significant changes
      were observed in the groups receiving PJ. CONCLUSIONS: The prophylactic
      consumption of PJ for 14 days could show nephroprotective effects by reducing
      oxidative stress and potassium depletion. It could also lead to the stabilization
      of kidney function during this period despite using captopril and gentamicin.

PMID- 29190607
TI  - Effect of Paricalcitol on Bone Density After Kidney Transplantation: Analysis of
      2 Transplant Centers.
AB  - INTRODUCTION: The Kidney Disease: Improving Global Outcomes Clinical Practice
      Guidelines on the management of bone disease in patients with chronic kidney
      disease recommend periodic measurement of serum calcium, phosphorus, vitamin D,
      and parathyroid hormone levels after kidney transplantation, with the frequencies
      that will vary according to the severity of bone disease and graft function.
      Paricalcitol, a selective vitamin D receptor activator, is indicated in the
      prevention and treatment of secondary hyperparathyroidism. MATERIALS AND METHODS:
      We retrospectively evaluated the effect of treatment with paricalcitol among our
      kidney transplant recipients. We monitored the effect of paricalcitol on bone
      density; the plasma levels of parathyroid hormone, calcium, and phosphorus; and
      proteinuria and calciuria. Comparisons were made between these parameters before
      treatment and 12 months after treatment. RESULTS: Eighty-eight kidney transplant
      recipients with a mean age at the time of transplantation of 47.1 +/- 10.5 years
      were receiving paricalcitol. On average, paricalcitol was included into the
      treatment for 48 months from transplantation (median, 27 months). The patients
      had significantly improved bone density (P < .001), significantly lower
      parathyroid hormone levels (P < .001), and significantly decreased proteinuria (P
      = .02) after 12 months of treatment. During the treatment with paricalcitol, the
      immunosuppressive therapy, dose of prednisone, body mass index, and vitamin D
      levels had not significantly changed. Nor had any significant change occurred to
      graft function. CONCLUSIONS: Paricalcitol is an effective therapy for secondary
      hyperparathyroidism in kidney transplant recipients.

PMID- 29190609
TI  - Nephroquiz 10: A 16-Year-Old Patient With Thrombocytopenia and Kidney Failure.

PMID- 29190603
TI  - Upregulation of Cabin1 During Injury to Renal Tubular Epithelial Cells in Rats.
AB  - INTRODUCTION: Calcineurin-binding protein 1 (Cabin1) interacts with calcineurin
      and p53, but its function in renal tubular epithelial cell (RTEC) is unclear. We
      established 5/6 nephrectomized rats and angiotensin II-induced injury to the
      RTECs in vitro, to observe the expression of Cabin1 during RTEC injury. MATERIALS
      AND METHODS: Sprague-Dawley rats were sacrificed at 4 and 8 weeks after 5/6
      nephrectomy. Renal pathology and mitochondrial damage were detected by light and
      electrical microscope. The distribution of E-cadherin and alpha-smad were
      detected by indirect immunofluorescence staining. Cabin1 protein expression was
      detected by Western blot. RESULTS: Obvious tubulointerstitial fibrosis was found
      in the nephrectomized rats at 8 weeks after 5/6 nephrectomy, accompanied by the
      increasing levels of creatinine, as well as the disruption of E-cadherin and
      overexpression of alpha-smad in RTECs. Moreover, the mitochondria became swollen
      and mitochondrial cristae were disrupted and poorly defined in the RTECs.
      Compared to the sham-operated rats, Cabin1 protein expression was significantly
      increased at 8 weeks after 5/6 nephrectomy, while angiotensin II-induced Cabin1
      protein expression significantly increased 48 hours after stimulation in normal
      rat kidney epithelial cells. CONCLUSIONS: Injury to the RTEC and Cabin1 protein
      overexpression occurred in a time-dependent manner both in vitro and in vivo.
      Cabin1 may become a potential molecular target in RTEC injury.

PMID- 29190608
TI  - Seropositivity of Rheumatoid Arthritis Specific Tests in a Patient With Nephrotic
      Syndrome: Successful Treatment With Rituximab.
AB  - Presentation of rheumatoid arthritis (RA) with renal complications is very rare
      without articular symptoms. We here report a case of a 23-year-old woman,
      presenting with the edema of the extremities, no relevant previous medical
      history, and the features of acute tubular injury in her percutaneous kidney
      biopsy. Following the incidental notification of a positive rheumatoid factor
      test, other immunologic tests including anticyclic citrullinated peptide and
      antimutated citrullinated vimentin were performed, the positive results of which
      favored the diagnosis of RA. Administration of rituximab led to the complete
      remission of the disease. Six weeks later, along with steroid dose reduction, the
      symptoms of arthralgia was observed, which was managed with methotrexate.
      Nephrotic syndrome could be rarely the first manifestation of RA, and screening
      of specific RA autoantibodies might be considered as part of diagnostic
      evaluations in nephrotic syndrome workup.

PMID- 29190605
TI  - Evaluation of Renal Toxicity of Colistin Therapy With Neutrophil Gelatinase
      associated Lipocalin: a Biomarker of Renal Tubular Damage.
AB  - INTRODUCTION: Nephrotoxicity has been a concern with new dosing regimens of
      colistin. This study was designed to compare nephrotoxicity of high dose and
      conventional dose of colistin and the ability of detecting it using neutrophil
      gelatinase-associated lipocalin (NGAL). MATERIALS AND METHODS: A randomized
      clinical trial was carried out on 40 patients with multidrug-resistant gram
      negative infections assigned into 2 groups to receive high and conventional doses
      of colistin. Blood samples were taken 4 times for measuring serum NGAL. The
      incidence of acute kidney injury was also evaluated based on the risk, injury,
      failure, loss, end-stage renal disease (RIFLE) criteria. RESULTS: Baseline levels
      of NGAL were not significantly different between the patients on the high dose
      and conventional dose of colistin. The mean NGAL levels on day 10 were 762.14 +/-
      415.44 pg/mL and 623.67 +/- 272.61 pg/mL, respectively.  However, between-group
      analysis did not show a significant difference in the NGAL levels. The prevalence
      of acute kidney injury was 60% and 15% based on the RIFLE criteria, in the high
      dose and conventional-dose groups, respectively (P = .003). CONCLUSIONS: Although
      colistin-induced nephrotoxicity was not confirmed with NGAL levels, our findings,
      however, showed a higher incidence of acute kidney injury associated with high
      dose colistin, defined by the RIFLE criteria. Higher levels of NGAL in the acute
      kidney injury patients were associated with high-dose regimen of colistin.

PMID- 29190606
TI  - Association Between Klotho Gene Polymorphism and Markers of Bone Metabolism in
      Patients Receiving Maintenance Hemodialysis in Iran.
AB  - INTRODUCTION: Some genetic variations of Klotho have been reported as a risk
      factor for calcification and hyperphosphatemia in chronic kidney disease. Klotho
      polymorphism is also associated with outcome in patients receiving hemodialysis.
      This study aimed to evaluate the relationship between Klotho single nucleotide
      polymorphism (SNP) and bone metabolism as an early prognostic measure for chronic
      kidney disease.   Materials and Methods. Sixty patients receiving hemodialysis
      and 60 age-matched controls were enrolled in the study of the assessment of 2
      types of Klotho polymorphism (G395A and C1818T). Serum biochemical parameters,
      including calcium, phosphate, urea, creatinine, parathyroid hormone, and 25
      hydroxyvitamin D3 were measured.  Results. The frequency of being A carriers
      suggested marginal significances between the groups (GA and AA, 30% versus GG,
      18.3%, P = .06), but such significant results were not found for the T allele
      carriers (CT and TT, 76.6% versus CC, 76.6%, P > .99). Homozygote and
      heterozygote individuals for the A allele at G395A SNP (A allele carriers) were
      more likely to be on hemodialysis (odds ratio, 1.43; 95% confidence interval,
      0.60 to 3.30), but this association was not true for T allele carriers of C1818T
      SNP. Parathyroid hormone and serum calcium, phosphate, creatinine, and urea
      showed prominently higher levels in the patients receiving hemodialysis compared
      with control individuals. CONCLUSIONS: The A allele of the G395A polymorphism of
      Klotho, which emerges the higher levels of phosphate, may be associated with the
      risk of mortality in Iranian patients receiving hemodialysis.

PMID- 29190612
TI  - Assessment of Bronchial Obstruction Using Lateral Pressure Measurement during
      Bronchoscopy.
AB  - BACKGROUND: In patients with bronchial obstruction estimating the location of the
      maximal obstruction is crucial for guiding interventional bronchoscopy. However,
      flow-volume curves cannot discriminate between the right and left lungs.
      OBJECTIVES: The aim of this study was to physiologically evaluate bronchial
      obstruction during interventional bronchoscopy. METHODS: We prospectively
      measured lateral airway pressure (Plat) at either side of the obstruction using a
      double-lumen catheter (pressure-pressure [P-P] curve) simultaneously to assess
      the degree of bronchial obstruction in 22 patients. The shape of the P-P curve
      was assessed to confirm the site of maximal obstruction. RESULTS: In the
      experimental study, Plat was uniform between both bronchi in the normal model.
      For the unilateral and bilateral obstruction models, a phase shift was only seen
      for the more obstructed side. In healthy subjects, the angle of the P-P curve was
      close to 45 degrees  and linear in shape. In patients with bronchial obstruction,
      the angle was much smaller but approached 45 degrees  after the bronchoscopic
      procedure. The degree of bronchial obstruction was significantly correlated with
      the angle of the P-P curve (r = -0.51, p < 0.01). Dyspnea significantly increased
      when the airway lumen was obstructed by more than 60% (p < 0.0001), and when the
      P-P curve appeared loop-shaped (p < 0.01). CONCLUSIONS: The shape of the P-P
      curve could be used to detect the site of maximal obstruction for the optimal
      positioning of the stent and assess the need for additional procedures in real
      time in patients with bronchial obstruction.

PMID- 29190604
TI  - Metabolic Response to Mulberry Extract Supplementation in Patients With Diabetic
      Nephropathy: a Randomized Controlled Trial.
AB  - INTRODUCTION: This study aimed to evaluate the effects of mulberry extract
      administration on markers of insulin metabolism, lipid concentrations, and
      biomarkers of inflammation and oxidative stress in patients with diabetic
      nephropathy (DN). MATERIALS AND METHODS: Sixty patients were randomly allocated
      into 2 groups to receive either 300 mg/d of mulberry extract (n = 30) or placebo
      (n = 30), twice per day for 12 weeks. Fasting blood samples were taken at the
      onset of the study and 12 weeks after supplementation to examine markers of
      insulin metabolism, lipid concentrations, and biomarkers of inflammation and
      oxidative stress. RESULTS: Mulberry extract, compared to placebo, resulted in
      significant reductions in serum triglycerides (-37.3 +/- 64.7 mg/dL versus 3.0 +/
      78.8 mg/dL, P = .03) and very low-density lipoprotein cholesterol (-7.4 +/- 12.9
      mg/dL versus 0.6 +/- 15.8 mg/dL, P = .03), and a significant increase in high
      density lipoprotein cholesterol concentration (0.5 +/- 4.0 mg/dL versus -2.0 +/-
      5.0 mg/dL, P = .03). Other significant changes were in serum high-sensitivity C
      reaction protein (-2.3 +/- 4.5 ug/mL versus -0.1 +/- 2.2 ug/mL, P = .02), plasma
      glutathione (87.8 +/- 159.7 umol/L versus -24.2 +/- 138.8 umol/L, P = .005) and
      malondialdehyde (-0.03 +/- 0.5 umol/L versus 0.7 +/- 1.0 umol/L, P < .001).  
      Conclusions. These findings showed that mulberry extract administration had
      favorable effects on serum lipids, HSCRP, glutathione, and malondialdehyde levels
      in DN patients; however, it did not affect markers of insulin metabolism or
      biomarkers of inflammation and oxidative stress.

PMID- 29190613
TI  - N-Terminal Prohormone of Brain Natriuretic Peptide but not C-Terminal Pre-Pro
      Vasopressin (Copeptin) Level is Associated with the Response to Antihypertensive
      Therapy in Haemodialysis Patients.
AB  - BACKGROUND/AIMS: Volume overload, frequently clinically asymptomatic is
      considered as a causative factor limiting the effectiveness of antihypertensive
      therapy in haemodialysis (HD) patients. Therefore, the aim of this study was to
      assess plasma levels of N-terminal fragment of the prohormone brain natriuretic
      peptide (NT-proBNP) and a C-terminal portion of the precursor of vasopressin (CT
      proAVP, copeptin), surrogate markers of volume overload in HD patients in
      relation to the number of antihypertensive drugs used in the hypertension
      treatment. METHODS: One hundred and fifty adult HD patients (92 males) were
      enrolled into this study. Clinical data concerning blood pressure (BP)
      measurements prior haemodialysis session and pharmacotherapy were collected from
      all patients. In addition to routine laboratory parameters, plasma levels of NT
      proBNP and CT-proAVP were measured, and daily sodium and water consumption were
      estimated with a portion-size food frequency questionnaire. RESULTS: Among 145
      (96.7%) hypertensive HD patients, 131 were receiving antihypertensive medication.
      Despite antihypertensive therapy, 31.0% had inadequate BP control. Plasma
      concentration of NT-proBNP was associated with systolic (R=0.19; p=0.02) but not
      diastolic BP values and with the number of received antihypertensive drugs
      (R=0.21; p=0.01). The highest NT-proBNP values were observed in patients
      receiving 3 or more antihypertensive drugs. In contrast, no significant
      correlation was found between plasma CT-proAVP concentrations and BP values as
      well as and the number of antihypertensive drugs. Receiver operator curve
      analysis showed that NT-proBNP values over 13,184 pg/mL predicted the use of at
      least 3 antihypertensive drugs in maximal doses in the therapy of hypertension,
      similar analyses performed for CT-proAVP showed much less specificity.
      CONCLUSIONS: 1. Increased levels of NT-proBNP seems to be a better biomarker of
      multidrug antihypertensive therapy requirement than CT-proAVP. 2. Whether
      estimation of NT-proBNP in these patients will be also better biomarker than
      copeptin in the prediction of cardiovascular complications related to
      hypertension needs further investigations.

PMID- 29190619
TI  - Ruptured de novo Aneurysm following Gamma Knife Surgery for Arteriovenous
      Malformation: Case Report.
AB  - Stereotactic radiosurgery is a well-known treatment tool for arteriovenous
      malformations (AVMs). The method has high validity and minimal invasiveness, but
      late-onset problems involving tumor formation and vasculopathy induced by
      radiation have been reported. We present a rare case of a radiation-induced
      ruptured de novo aneurysm following Gamma Knife surgery (GKS) for an AVM. A 17
      year-old, right-handed male underwent GKS for AVM at the left parietal lobe.
      After 3 years, a follow-up angiogram showed a residual AVM at the angular gyrus.
      Then, a 2nd GKS was performed for the residual lesion. Six years after the 1st
      GKS, the AVM disappeared on the angiogram. Seven years later, he suffered a
      sudden onset of headache. A left carotid angiogram revealed a ruptured aneurysm
      at the M2-M3 junction of the middle cerebral artery parietal branch. Coil
      embolization was performed, and the aneurysm was occluded. The patient was
      discharged without any neurologic deficits.

PMID- 29190620
TI  - Four Novel NR5A1 Mutations in 46,XY Gonadal Dysgenesis Patients Including
      Frameshift Mutations with Altered Subcellular SF-1 Localization.
AB  - 46,XY gonadal dysgenesis (46,XY GD) is a disorder of sexual development caused by
      mutations in genes involved in early gonadal development (bipotential gonads) and
      testis differentiation. In 46,XY GD individuals, mutations of the SRY gene are
      detected most frequently, followed by mutations in the NR5A1 (SF-1) gene, but in
      a lot of cases, the underlying molecular mechanism remains elusive. In this
      study, we retrospectively performed sequence analyses of the NR5A1 (SF-1) gene in
      84 patients with complete, partial, and syndromic forms of 46,XY GD. In total, 7
      heterozygous mutations were found in 6 of 84 patients (7.1%). Among these, we
      identified 4 mutations that, to the best of our knowledge, have not been reported
      before (c.268G>T, c.369del, c.871-1G>C, and c.893T>C). Transfection of different
      mutations revealed altered subcellular localization of the mutant SF-1 protein in
      the case of the frameshift mutations, indicating an impaired protein function. In
      conclusion, we present 4 novel mutations of the NR5A1 gene associated with 46,XY
      GD together with in vitro data pointing towards a possible functional impairment
      of the mutant SF-1 proteins.

PMID- 29190614
TI  - How Survey Design Affects Monkey Counts: A Case Study on Individually Recognized
      Spider Monkeys (Ateles geoffroyi).
AB  - The fast movement and high degree of fission-fusion dynamics of spider monkeys
      (Ateles spp.) make them notoriously difficult to survey. We examined which
      aspects of survey design affect spider monkey sightings along transects in a
      group of individually recognized spider monkeys (Ateles geoffroyi) in Punta
      Laguna, Yucatan, Mexico. We calculated the number of monkeys and subgroups
      sighted per transect walk. Using generalized linear models, we found no effect of
      the number of observers, transect type (new vs. existing), walking speed, or time
      of day on individual monkey counts or subgroup counts. Recounting of individuals
      was relatively rare and occurred when transects were walked relatively slowly. We
      missed more young than adult monkeys. The group composition based on survey data
      was similar to the known group composition. Based on our findings we recommend
      that surveys performed on relatively flat terrain be conducted at speeds similar
      to or faster than the moving speed of spider monkeys to minimize recounting of
      individuals and that young:adult female ratios based on survey data be
      interpreted as conservative indicators of population health. The novel methods
      presented to determine sources of bias in population estimates are applicable to
      a wide range of primates that are difficult to survey.

PMID- 29190616
TI  - Apatinib Inhibits Angiogenesis Via Suppressing Akt/GSK3beta/ANG Signaling Pathway
      in Anaplastic Thyroid Cancer.
AB  - BACKGROUND/AIMS: Anaplastic thyroid carcinoma (ATC) is one of the most lethal
      human malignancies, and there is no efficient method to slow its process.
      Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its
      efficacy and safety in the treatment of advanced gastric carcinoma patients.
      However, the effects of Apatinib in ATC are still unknown. METHODS: In this
      study, we explored the effects and mechanisms of Apatinib on tumor growth and
      angiogenesis in vitro and in vitro in ATC cells. Angiogenesis antibodies array
      was utilized to detect the expression of angiogenesis-related genes after
      Apatinib treatment in ATC cells. In addition, we used Akt activator, Akt
      inhibitor and GSK3beta inhibitor to further study the mechanism for how Apatinib
      suppressed angiogenesis. RESULTS: Apatinib treatment could suppress the growth of
      ATC cells in a dose- and time-dependent manner via inducing apoptosis and
      blocking cell cycle progression at G0/G1 phase. Moreover, Apatinib treatment
      decreased the expression of angiogenin (ANG) and inhibited angiogenesis of ATC
      cells in vitro and in vitro. We further confirmed that recombinant human ANG
      (rhANG) significantly abrogated Apatinib-mediated anti-angiogenic ability in ATC
      cells. Additionally, Apatinib treatment decreased the level of p-Akt and p
      GSK3beta. Moreover, the Apatinib-mediated decrease of ANG and anti-angiogenic
      ability were partly reversed when an Akt activator, SC79, was administered.
      Furthermore, the anti-angiogenic ability of Apatinib can be enhanced in the
      presence of Akt inhibitor, and the inhibition of GSK3beta attenuated the anti
      angiogenic ability of Apatinib. CONCLUSION: Our results demonstrated that
      Apatinib treatment inhibited tumor growth, and Apatinib-induced suppression of
      Akt/GSK3beta/ANG signaling pathway may play an important role in the inhibition
      of angiogenesis in ATC, supporting a potential therapeutic approach for using
      Apatinib in the treatment of ATC.

PMID- 29190615
TI  - The Key Roles of GSK-3beta in Regulating Mitochondrial Activity.
AB  - Glycogen synthase kinase-3beta (GSK-3beta), a serine/threonine protein kinase,
      has been reported to show essential roles in molecular pathophysiology of many
      diseases. Mitochondrion is a dynamic organelle for producing cellular energy and
      determining cell fates. Stress-induced translocated GSK-3beta may interact with
      mitochondrial proteins, including PI3K-Akt, PGC-1alpha, HK II, PKCepsilon,
      components of respiratory chain, and subunits of mPTP. Mitochondrial pool of GSK
      3beta has been implicated in mediation of mitochondrial functions. GSK-3beta
      exhibits the regulatory effects on mitochondrial biogenesis, mitochondrial
      bioenergetics, mitochondrial permeability, mitochondrial motility, and
      mitochondrial apoptosis. The versatile functions of GSK-3beta might be associated
      with its wide range of substrates. Accumulative evidence demonstrates that GSK
      3beta inactivation may be potentially developed as the promising strategy in
      management of many diseases, such as Alzheimer's disease (AD) and Parkinson's
      disease (PD). Intensive efforts have been made for exploring GSK-3beta
      inhibitors. Natural products provide us a great source for screening new lead
      compounds in inactivation of GSK-3beta. The key roles of GSK-3beta in mediation
      of mitochondrial functions are discussed in this review.

PMID- 29190622
TI  - Classifying Apnea of Prematurity by Transcutaneous Electromyography of the
      Diaphragm.
AB  - BACKGROUND: Treatment of apnea is highly dependent on the type of apnea. Chest
      impedance (CI) has inaccuracies in monitoring respiration, which compromises
      accurate apnea classification. Electrical activity of the diaphragm measured by
      transcutaneous electromyography (EMG) is feasible in preterm infants and might
      improve the accuracy of apnea classification. OBJECTIVES: To compare the accuracy
      of apnea classification based on diaphragmatic EMG (dEMG) and CI tracings in
      preterm infants. METHODS: Fifteen cases of central apnea, 5 of obstructive apnea,
      and 10 of mixed apnea were selected from recordings containing synchronized
      continuous tracings of respiratory inductive plethysmography (RIP), airway flow,
      heart rate (HR), oxygen saturation (SpO2), and breathing activity measured by
      dEMG and CI. Twenty-two assessors (neonatologists, pediatricians-in-training, and
      nurses) classified each apnea twice; once based on dEMG, HR, and SpO2 tracings,
      and once based on CI, HR, and SpO2. The assessors were blinded to the type of
      respiratory tracing (dEMG or CI) and to the RIP and flow tracings. RESULTS: In
      total 1,320 assessments were performed, and in 71.1% the apnea was classified
      correctly. Subgroup analysis based on respiratory tracing showed that 74.8% of
      the dEMG tracings were classified correctly compared to 67.3% of the CI tracings
      (p < 0.001). This improved apnea classification based on dEMG was present for
      central (86.7 vs. 80.3%, p < 0.02) and obstructive (56.4 vs. 32.7%, p < 0.001)
      apnea. The improved apnea classification based on dEMG tracing was independent of
      the type of assessor. CONCLUSION: Transcutaneous dEMG improves the accuracy of
      apnea classification when compared to CI in preterm infants, making this
      technique a promising candidate for future monitoring systems.

PMID- 29190611
TI  - Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma
      Through Inhibition of P53.
AB  - BACKGROUND/AIMS: The tripartite motif containing (TRIM) family plays crucial
      roles in tumor development and progression. However, little is known about the
      function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). METHODS: The
      expression levels of TRIM11 were examined by real-time PCR, Western blot and
      Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by
      lentivirus infection, and functional assays, such as MTT, colony formation assay,
      migration and invasion assays and a xenograft tumor model were used to
      investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on
      p53 signaling and its downstream molecules. RESULTS: We found that TRIM11 mRNA
      and protein levels were significantly increased in HCC tissues as compared with
      normal tissues; increased levels correlated with poor patient survival. By loss-
      and gain-of-function investigations, knockdown of TRIM11 suppressed cell
      proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover,
      TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in
      vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. CONCLUSIONS:
      These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating
      p53 both in vitro and in vivo. Our data provide new insights into the
      pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic
      target for HCC treatment.

PMID- 29190621
TI  - NSCLC Patients Harbouring Rare or Complex EGFR Mutations Are More Often Smokers
      and Might Not Benefit from First-Line Tyrosine Kinase Inhibitor Therapy.
AB  - BACKGROUND: Generally, tyrosine kinase inhibitor (TKI) therapy is recommended in
      first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)
      harbouring a classic epidermal growth factor receptor (EGFR) mutation. However,
      the response of patients with rare or complex EGFR mutations to TKI treatment is
      not predictable, nor is the prognosis for such patients. OBJECTIVES: In cases of
      rare or complex EGFR mutations, the right approach to therapy remains
      challenging. That is why we sought to analyse the characteristics as well as the
      prognosis and the response to TKI treatment of patients with rare or complex EGFR
      mutations. PATIENTS AND METHODS: 343 NSCLC patients tested for EGFR mutation at a
      German lung cancer centre were analysed for age, gender, and smoking status as
      well as for the mutation status. For 12 patients with rare and complex mutations,
      response to TKI treatment was described. RESULTS: 282 of all patients had a wild
      type EGFR, whereas 61 harboured an EGFR mutation. 32 of these were classic
      mutations, followed by 16 rare and 7 complex mutations. EGFR mutations were
      significantly more frequent in women. Patients with rare or complex mutations
      were significantly more often smokers compared to those with classic EGFR
      mutations. Furthermore, rare and complex mutations were less responsive to TKI
      therapy. CONCLUSION: Patients with rare or complex EGFR mutations differ from
      those with classic mutations in terms of smoking status and response to TKIs. As
      these mutations may not respond well to TKI therapy, first-line TKIs should not
      be automatically chosen based on the sole presence of an EGFR mutation.

PMID- 29190623
TI  - Axial Length/Corneal Radius of Curvature Ratio Assessment of Posterior Sclera
      Reinforcement for Pathologic Myopia.
AB  - PURPOSE: The aim of this study was to assess the axial length/corneal radius of
      curvature ratio changes after posterior scleral reinforcement (PSR) for
      pathologic myopia. PROCEDURES: This study enrolled 32 pathologically myopic eyes
      treated with PSR and 35 untreated pathologically myopic eyes. Axial length,
      refractive error, best corrected visual acuity, corneal radius of curvature, and
      the axial length/corneal radius of curvature ratio were evaluated during the 1
      year follow-up. RESULTS: There were no statistical differences in each parameter
      between the 2 groups at baseline. Significant differences were found between the
      2 groups in both axial elongation and best corrected visual acuity improvement.
      The average axial length/horizontal corneal radius of curvature ratio
      significantly decreased in the PSR group. CONCLUSION: The PSR surgery can
      effectively delay the axial elongation in pathological myopia. Axial
      length/horizontal corneal radius of curvature ratio significantly decreased,
      which may indicate less myopic progression after surgery.

PMID- 29190624
TI  - Extreme Surgical Maneuvers in Fungal Endophthalmitis.
AB  - PURPOSE: To present the different evolution of 2 cases of endophthalmitis caused
      by Fusarium solani, an aggressive filamentous fungus, depending on the medical
      and surgical treatment performed. METHODS: We present 2 cases of endophthalmitis
      caused by Fusarium solani. Topical, intrastromal, intravitreal, and systemic
      antifungal treatment (natamycin, voriconazole, amphotericin B) failed in both
      cases. Corneal perforation took place in one of them, being unsuccessfully
      treated with cyanoacrylate and several amniotic membrane transplants. It became
      necessary to perform a hot penetrating keratoplasty (PK) in both patients. The
      lenses were removed, and the microbiological analysis showed their colonization
      by Fusarium solani. In one of the cases, a second PK and a more aggressive pars
      plana vitrectomy (PPV) were performed after corneal recurrence detected by
      confocal microscopy, as well as the following therapeutic intra- and
      postoperative maneuvers: anterior chamber washing with povidone-iodine 5% for 1
      min; iridectomy of the infiltrated regions; aspiration of the fungal colonies
      with vitrector; several air/fluid/amphotericin/voriconazole exchanges during PPV;
      endodiathermy and endophotocoagulation of the chorioretinitis foci; and
      intrascleral angle injections of voriconazole and amphotericin. RESULTS: These
      were the only cases of endophthalmitis caused by Fusarium attended to at our
      hospital during the last 10 years. In the case in which PPV was performed without
      those maneuvers, endophthalmitis rapidly recurred in a more aggressive way, so
      finally it became necessary to eviscerate the globe. On the other hand, in the
      patient who underwent PPV with the specific surgical maneuvers and postoperative
      procedures described above, we could preserve the eye and even a vision of hand
      motion without an intraocular lens. CONCLUSIONS: The main objectives of these
      surgical procedures are to control the fungal infection and to preserve the
      ocular globe. It is essential to eliminate all ocular structures (iris, lens,
      vitreous, etc.) affected by this strain of fungus in order to reduce the risk of
      recurrence. When indicated, early surgery with the appropriate maneuvers detailed
      above may make an evisceration unnecessary and even recover some visual acuity.

PMID- 29190627
TI  - Gender-Related Differences and Short-Term Outcome of Stroke: Results from a
      Hospital-Based Registry in Sub-Saharan Africa.
AB  - BACKGROUND: Studies suggest that sex differences have an impact on patients with
      stroke, but existing data in Africa remain inconclusive about this inference.
      OBJECTIVES: To study sex differences in terms of the clinical profile and short
      term outcome of stroke in the Douala General Hospital, Cameroon. METHODS: A
      hospital-based prospective cohort study was carried out in a tertiary care
      hospital over an 8-year period, which included all patients admitted for
      confirmed acute stroke. Information about the history of stroke with emphasis on
      clinical profile and outcome was collected. Descriptive statistics, t test, and
      chi square test were used for comparisons, while the Kaplan-Meier curve was used
      for survival rate analysis. RESULTS: Of the 818 patients included, 455 (55.6%)
      were male patients. When compared to males, female patients are more likely to
      experience a stroke at an older age (mean age 62.3 +/- 14.1 vs. 58.4 +/- 12.9
      years, p < 0.001), to be unmarried, to remain unemployed, and to have higher
      rates of cardio-embolic stroke (p = 0.049), body mass index (p = 0.031), altered
      levels of consciousness at presentation (p = 0.005), higher mean HDL cholesterol
      levels (p = 0.001), and in-hospital complications (p = 0.011), especially urinary
      tract infections (p = 0.018). Males were more likely to have health insurance, to
      smoke, to consume alcohol (p < 0.001), and to have higher rates of dysarthria (p
      = 0.004), higher mean uric acid (p = 0.013), and creatinine (p < 0.001)
      concentrations. Ischemic and hemorrhagic strokes were more prevalent in men (p =
      0.003). There are no sex differences in terms of stroke severity, length-of
      hospital stay, case fatality, and functional outcome on admission. CONCLUSIONS:
      Sex differences exist in the clinical profile of stroke but not in the outcome.
      Knowledge of these differences could help influence stroke prevention, thereby
      improving stroke burden in Africa.

PMID- 29190631
TI  - A Retrospective Review of the Diagnostic and Management Challenges of Mirizzi
      Syndrome at the Singapore General Hospital.
AB  - BACKGROUND: Mirizzi syndrome (MS) occurs when gallstone impaction in Hartmann's
      pouch results in extrinsic obstruction of the common bile duct, and fistulation
      may occur. METHODS: We retrospectively reviewed electronic records of patients
      surgically treated for MS from November 2001 to June 2012. Patient presentations,
      diagnostic methods, treatments and complications were recorded. RESULTS: Sixty
      four patients were grouped according to a classification proposed by Beltran et
      al. [World J Surg 2008; 32: 2237-2243]. Forty-three (66.2%), 18 (27.7%) and 3
      (4.6%) patients were classified as types I, II, and III respectively. Magnetic
      resonance-cholangiopancreaticography was the most sensitive imaging modality,
      suggesting MS in 24 (88.9%), followed by CT scan (40%) and ultrasonography
      (11.4%). Forty-four underwent Endoscopic-retrograde-cholangiopancreaticography
      and 29 (65.9%) suggested the presence of MS. MS was accurately diagnosed pre
      operatively in 48 (73.8%) patients. In type I, 40 (93.0%) patients underwent
      cholecystectomy, while 3 required hepaticojejunostomy. In type II, 12 (66.7%)
      underwent cholecystectomy and 5 (27.8%) required hepatico-enteric anastomosis. In
      type III, 1 underwent cholecystectomy and 2 (66.7%) required hepatico-enteric
      anastomosis. Laparoscopic cholecystectomy was attempted in 20 (30.8%) patients
      and 13 (65.0%) required conversion. Twenty-nine (44.6%) underwent intra-operative
      cholangioscopy, 30 (46.2%) underwent intra-operative-cholangiogram and 41 (63.1%)
      underwent intra-operative T-tube placement. Six (9.2%) experienced intra
      operative complications, 12 (18.5%) experienced post-operative complications and
      10 (15.4%) experienced late complications. CONCLUSION: MS is a challenging
      condition and multimodal diagnostic approach has the greatest yield in achieving
      accurate pre-operative diagnosis. If suspicion is high, a trial of laparoscopic
      dissection with low threshold for open conversion is recommended.

PMID- 29190632
TI  - Tinnitus Is Associated with a Higher Risk of Benign Brain Tumors: A Nationwide,
      Population-Based Secondary Cohort Study of Young and Middle-Aged Adults.
AB  - BACKGROUND: It remains unclear whether tinnitus is associated with a higher risk
      of benign or malignant brain tumors in humans. Therefore, the aim of this
      secondary study was to investigate the risk of brain tumors in adult with
      tinnitus using data from a nationwide health claims research database. METHODS:
      Patients aged 20-50 years who were newly diagnosed with tinnitus were identified
      from the Taiwan's National Health Insurance Research Database and they served as
      the study cohort. A comparison cohort was formed by using patients without
      tinnitus from the same database with frequency matching (4: 1) by 10-year age
      interval and gender to the patients in the tinnitus cohort. Cox proportional
      hazards models were used to calculate the adjusted hazard ratios (AHR) for benign
      and malignant brain tumors in patients with tinnitus, adjusting for age, gender,
      and comorbidities. RESULTS: There were 15,819 patients in the tinnitus cohort and
      63,276 in the comparison cohort. A significantly higher proportion of patients
      with tinnitus had benign brain tumor (p = 0.003) and all 11 comorbid conditions
      (p < 0.001) compared to those without tinnitus. Cox proportional hazards
      regression analysis performed on the basis of age, gender, and the 11
      comorbidities revealed that tinnitus was independently associated with a higher
      risk for benign brain tumor (AHR 1.65, 95% CI 1.24-2.20, p = 0.001) and but not
      with malignant brain tumors (AHR 1.66, 95% CI 0.93-2.94, p = 0.085). CONCLUSIONS:
      Findings from this secondary cohort analysis indicated that tinnitus is
      associated with a higher risk of benign brain tumors.

PMID- 29190629
TI  - Suppressed Adiponectin Levels and Increased Adiponectin Response to Oral Glucose
      Load in Lean Women with Severe Acne Normalizes after Isotretinoin Treatment.
AB  - BACKGROUND/AIM: Isotretinoin, the drug of choice for severe acne, might be
      associated with a decrease in insulin sensitivity. Adiponectin is an adipose
      tissue-derived protein that increases insulin sensitivity. In this study, we
      aimed to investigate adiponectin levels in postadolescent severe acne and the
      effect of isotretinoin on adiponectin levels. METHODS: Participants included 18
      female patients with severe acne and 18 healthy women matched for age and body
      mass index (BMI). Acne patients completed a 6-month isotretinoin treatment.
      Anthropometric measurements, serum adiponectin, lipids, fasting glucose, fasting
      insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were
      determined, and a standard 2-h oral glucose tolerance test (OGTT) was performed
      in healthy women once and in patients with acne before and after treatment.
      RESULTS: At baseline, patients with acne had significantly lower serum
      adiponectin levels than controls. Isotretinoin treatment resulted in a
      significant increase in weight, BMI, and triglyceride and adiponectin levels.
      Glucose metabolism markers in patients with acne and controls were similar at
      baseline and did not change after treatment. Baseline OGTT in acne patients
      revealed an increased adiponectin response at 2 h, which was not present in
      healthy controls. Remarkably, this OGTT-induced adiponectin increment in acne
      patients was diminished after isotretinoin treatment. CONCLUSION: Adiponectin
      levels are differently regulated in women with severe acne and healthy controls
      in that circulating basal levels in patients are suppressed and show an increase
      in response to oral glucose load. Suppression of baseline adiponectin ameliorates
      after 6 months of isotretinoin treatment, reaching levels similar to those of
      healthy controls.

PMID- 29190635
TI  - Neonatal lupus - case series of a tertiary hospital.
AB  - Neonatal lupus (NL) is a very rare condition with an estimated incidence of 1 in
      20.000 pregnancies. It is caused by the transplacental passage of autoantibodies
      anti-Ro/SSA, antiSa/SSB antibodies and/or anti-U1 RNP antibodies into the fetal
      circulation. The mother may be completely asymptomatic or have a known
      inflammatory rheumatic disease, such as Sjogren syndrome (SS) or Systemic Lupus
      Erythematosus (SLE). Clinical manifestations are diverse, being the most common
      cutaneous and cardiac. The authors present a case series of eight cases diagnosed
      with NL between January 2008 and December 2016 in a tertiary hospital and a brief
      revision of the literature.

PMID- 29190628
TI  - Cord Blood Biomarkers of Cardiac Dysfunction and Damage in Term Growth-Restricted
      Fetuses Classified by Severity Criteria.
AB  - OBJECTIVE: To assess cardiovascular function and damage in term small-for
      gestational-age (SGA) and intrauterine growth-restricted (IUGR) fetuses by
      echocardiography and biomarkers in cord blood. METHODS: This was a cohort study
      including 60 normal fetuses and 47 term small fetuses subclassified as small for
      gestational age (SGA) with estimated fetal weight (EFW) between the 3rd and 9th
      centiles and normal fetoplacental Doppler (n = 14) or intrauterine growth
      restriction (IUGR, n = 33) if EFW <3rd centile or EFW <10th centile together with
      cerebroplacental ratio <5th and/or mean uterine artery pulsatility index >95th
      centile. Fetal echocardiography included left myocardial performance index (MPI)
      and annular plane systolic excursion. Fetal B-type natriuretic peptide (BNP),
      troponin-I, heart-type fatty acid-binding proteins (H-FABP), and homocysteine
      concentrations were measured in cord blood collected at delivery. RESULTS: Both
      SGA and IUGR cases presented echocardiographic signs of systolic and diastolic
      dysfunction with increased MPI (mean controls 0.43 [SD 0.12], SGA 0.47 [0.03],
      and IUGR 0.57 [0.08], p < 0.01) and decreased mitral annular plane systolic
      excursion (controls 6.0 mm [1.0], SGA 5.5 mm [0.6], and IUGR 4.9 mm [0.8], p = 0
      01). IUGR fetuses presented increased levels of cord blood BNP (controls 17.2
      pg/mL [11.5], SGA 22.4 pg/mL [10.7], and IUGR 31.2 pg/mL [26.8], p < 0.01).
      Troponin I was increased in both SGA and IUGR cases (controls 0.004 ng/mL
      [0.007], SGA 0.012 ng/mL [0.02], and IUGR 0.018 ng/mL [0.05], p < 0.01). H-FABP
      and homocysteine showed similar values among groups. CONCLUSIONS: Cardiac
      dysfunction and cell damage is a common feature of term SGA and IUGR fetuses
      despite of the severity criteria for perinatal outcome. Further research is
      needed to evaluate the potential long-term consequences on their cardiovascular
      system.

PMID- 29190626
TI  - SPARCL1, a Novel Prognostic Predictive Factor for GI Malignancies: a Meta
      Analysis.
AB  - BACKGROUND/AIMS: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1)
      is abnormally expressed in gastrointestinal (GI) malignancies. However, the
      correlation between SPARCL1 expression and the prognosis of patients remains
      unknown. Therefore, we performed a meta-analysis to investigate the potential
      value of SPARCL1 as a prognostic predictive marker for GI malignancies. METHODS:
      The PubMed, Embase, EBSCO, CNKI, and Wanfang databases were systematically
      searched for studies examining SPARCL1 and clinicopathological features,
      including the prognoses of patients. Hazard ratios (HRs) and odds ratios (ORs)
      from individual studies were calculated and pooled using a random-effects or fix
      effects model. Heterogeneity and publication bias analyses were performed.
      RESULTS: Data from 8 studies, including a total of 2,356 patients, were
      summarized. The expression of SPARCL1 suggested a better prognosis (HR=0.57, 95%
      CI: 0.445-0.698, P=0.000) and was associated with clinicopathological features of
      GI malignancies, including distant metastasis (OR=0.44, 95% CI: 0.23-0.85,
      P=0.014), lymph node metastasis (OR=0.56, 95% CI: 0.39-0.81, P=0.002) and tumor
      differentiation (OR=2.21, 95% CI: 1.82-2.69, P=0.000). Subgroup analyses based on
      cancer type revealed that the expression of SPARCL1 had no effect on lymph node
      metastasis in colorectal cancer, and it did not influence tumor differentiation
      in gastric cancer. Egger's test showed no evidence of publication bias (all
      P>0.05). CONCLUSION: SPARCL1 could be a novel prognostic predictive factor for GI
      malignancies. The expression of SPARCL1 could influence the clinicopathological
      features of GI malignancies. Further large-scale studies are essential to confirm
      SPARCL1's prognostic predictive value, and more fundamental experimental studies
      are needed to illustrate the mechanisms.

PMID- 29190625
TI  - mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review.
AB  - The mechanistic target of rapamycin (mTOR) network is an evolutionary conserved
      signaling hub that senses and integrates environmental and intracellular nutrient
      and growth factor signals to coordinate basic cellular and organismal responses
      such as cell growth, proliferation, apoptosis, and inflammation depending on the
      individual cell and tissue. A growing list of evidence suggests that mTOR
      signaling influences longevity and aging. Inhibition of the mTOR complex 1
      (mTORC1) with rapamycin is currently the only known pharmacological treatment
      that increases lifespan in all model organisms studied. This review discusses the
      potential mechanisms how mTOR signaling controls lifespan and influences aging
      related processes such as cellular senescence, metabolism, and stem cell
      function. Understanding these processes might provide novel therapeutic
      approaches to influence longevity and aging-related diseases.

PMID- 29190634
TI  - Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External
      Ophthalmoplegia and Mitochondrial DNA A3243G Mutation.
AB  - Focal segmental glomerulosclerosis (FSGS) is caused by various etiologies, with
      mitochondrial dysfunction being one of the causes. FSGS is known to be associated
      with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
      (MELAS), which is a subclass of mitochondrial disease. However, it has rarely
      been reported in other mitochondrial disease subclasses. Here, we reported a 20
      year-old man diagnosed with FSGS associated with chronic progressive external
      ophthalmoplegia (CPEO) due to mitochondrial DNA (mtDNA) 3243A>G mutation. He
      presented with left ptosis, short stature, mild sensorineural deafness, and
      cardiac conduction block. A renal biopsy sample showed segmental sclerosis and
      adhesions between capillaries and Bowman's capsule, indicating FSGS. Electron
      microscopy demonstrated abnormal aggregated mitochondria in podocytes, and the
      basement membrane and epithelial cells of Bowman's capsule. Skeletal muscle
      biopsy also showed accumulation of abnormal mitochondria. mtDNA analysis
      identified heteroplasmic mtDNA 3243A>G mutation with no large-scale deletions.
      From these findings, we diagnosed the case as CPEO with multi-organ involvement
      including FSGS. Our report demonstrates that CPEO, as well as MELAS, can be
      associated with FSGS. Because mitochondrial disease presents with a variety of
      clinical symptoms, atypical cases with non-classical manifestations are observed.
      Thus, mitochondrial disease should be considered as an underlying cause of FSGS
      with systemic manifestations even with atypical phenotypes.

PMID- 29190638
TI  - Linking gene dynamics to vascular hyperplasia - Toward a predictive model of vein
      graft adaptation.
AB  - Reductionist approaches, where individual pieces of a process are examined in
      isolation, have been the mainstay of biomedical research. While these methods are
      effective in highly compartmentalized systems, they fail to account for the
      inherent plasticity and non-linearity within the signaling structure. In the
      current manuscript, we present the computational architecture for tracking an
      acute perturbation in a biologic system through a multiscale model that links
      gene dynamics to cell kinetics, with the overall goal of predicting tissue
      adaptation. Given the complexity of the genome, the problem is made tractable by
      clustering temporal changes in gene expression into unique patterns. These
      cluster elements form the core of an integrated network that serves as the
      driving force for the response of the biologic system. This modeling approach is
      illustrated using the clinical scenario of vein bypass graft adaptation. Vein
      segments placed in the arterial circulation for treatment of advanced occlusive
      disease can develop an aggressive hyperplastic response that narrows the lumen,
      reduces blood flow, and induces in situ thrombosis. Reducing this hyperplastic
      response has been a long-standing but unrealized goal of biologic researchers in
      the field. With repeated failures of single target therapies, the redundant
      response pathways are thought to be a fundamental issue preventing progress
      towards a solution. Using the current framework, we demonstrate how theoretical
      genomic manipulations can be introduced into the system to shift the adaptation
      to a more beneficial phenotype, where the hyperplastic response is mitigated and
      the risk of thrombosis reduced. Utilizing our previously published rabbit vein
      graft genomic data, where grafts were harvested at time points ranging from 2
      hours to 28 days and under differential flow conditions, and a customized
      clustering algorithm, five gene clusters that differentiated the low flow (i.e.,
      pro-hyperplastic) from high flow (i.e., anti-hyperplastic) response were
      identified. The current analysis advances these general associations to create a
      model that identifies those genes sets most likely to be of therapeutic benefit.
      Using this approach, we examine the range of potential opportunities for
      intervention via gene cluster over-expression or inhibition, delivered in
      isolation or combination, at the time of vein graft implantation.

PMID- 29190633
TI  - Contractile Responses in Spontaneously Hypertensive Rats after Transient Middle
      Cerebral Artery Occlusion.
AB  - Stroke is one of the leading causes of mortality and morbidity worldwide, and few
      therapeutic treatments have shown beneficial effect clinically. One reason for
      this could be the lack of risk factors incorporated into the preclinical stroke
      research. We have previously demonstrated phenotypic receptor changes to be one
      of the injurious mechanisms occurring after stroke but mostly in healthy rats.
      The aim of this study was to investigate if hypertension has an effect on
      vasoconstrictive receptor responses to endothelin 1, sarafotoxin 6c and
      angiotensin II after stroke by inducing transient middle cerebral artery
      occlusion in spontaneously hypertensive rats and Wistar-Kyoto rats using the wire
      myograph. We demonstrated an increased contractile response to endothelin 1 and
      extracellular potassium as well as an increased carbachol-induced dilator
      response in the middle cerebral arteries from hypertensive rats after stroke.
      This study demonstrates the importance of including risk factors in experimental
      stroke research.

PMID- 29190630
TI  - Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by
      Targeting MEK/ERK Expression and MMP-9 Transcription Activity.
AB  - BACKGROUND/AIMS: alpha-mangostin has anti-carcinogenic effects against several
      cancers. We investigated the molecular mechanism of this compound on the
      metastasis of human renal carcinoma cells. METHODS: Cell viability was measured
      using the MTT assay, and cell cycle distribution using flow cytometry. A Matrigel
      based assay was used to measure in vitro cell migration and invasion. MAPK
      related proteins and matrix metalloproteinase (MMP)-9 and MMP-2 expression were
      measured by western blotting, and MMP2/-9 activities were determined by gelatin
      zymography. RT-qPCR and a luciferase assay were used to examine the
      transcriptional activity of MMP-9. RESULTS: alpha-mangostin inhibited the
      migration and invasion of RCC cells in a dose-dependent manner, but had no
      evident cytotoxic effects. Treatment of 786-O cells with alpha-mangostin
      inhibited activation of MEK and ERK. Treatment with a specific MEK inhibitor
      (U0126) enhanced the inhibitory effects of alpha-mangostin on cell migration and
      invasion, and the phosphorylation of ERK and MEK. Moreover, alpha-mangostin
      inhibited the expression of the MMP-9 mRNA levels as well as the activity of MMP
      9 promoter, and these suppressive effects were further enhanced by U0126.
      CONCLUSIONS: Our results suggest that alpha-mangostin suppresses cell migration
      and invasion via MEK/ERK/MMP9 pathway, and might be a promising anti-metastatic
      agent against human renal cell carcinoma.

PMID- 29190637
TI  - Standard-dose osimertinib for refractory leptomeningeal metastases in T790M
      positive EGFR-mutant non-small cell lung cancer.
AB  - BACKGROUND: Osimertinib demonstrated promising efficacy for refractory
      leptomeningeal metastases (LM) in preclinical data and a clinical study at 160
      mg, but there is limited data for the standard 80 mg dose. METHODS: T790M
      positive patients with suspected LM after classical epidermal growth factor
      receptor-tyrosine kinase inhibitor (EGFR-TKI) failure were enroled. RESULTS: We
      investigated 13 patients (5 definitive and 8 possible LM cases). In two of the
      five definitive cases with T790M in and outside the central nervous system (CNS),
      osimertinib was effective for both lesions, with cerebrospinal fluid (CSF)
      clearance of cancer cells and sensitive/T790M mutations. In three definitive
      cases with extra-CNS T790M without CSF T790M, cancer cells and sensitive
      mutations in the CSF persisted after osimertinib initiation. The median
      progression-free survival of all 13 patients was 7.2 months. Osimertinib was
      generally well-tolerated despite poor performance status, but interstitial lung
      disease (grade 2) was confirmed in one patient. Based on 25 samples from 13
      patients, the osimertinib CSF penetration rate was 2.5+/-0.3%. CONCLUSIONS:
      Osimertinib 80 mg is a useful therapeutic option for refractory LM after
      classical EGFR-TKI failure. It appears more effective in CSF T790M-positive
      cases.

PMID- 29190636
TI  - Tumour budding in oral squamous cell carcinoma: a meta-analysis.
AB  - BACKGROUND: Tumour budding has been reported as a promising prognostic marker in
      many cancers. This meta-analysis assessed the prognostic value of tumour budding
      in oral squamous cell carcinoma (OSCC). METHODS: We searched OvidMedline, PubMed,
      Scopus and Web of Science for articles that studied tumour budding in OSCC. We
      used reporting recommendations for tumour marker (REMARK) criteria to evaluate
      the quality of studies eligible for meta-analysis. RESULTS: A total of 16 studies
      evaluated the prognostic value of tumour budding in OSCC. The meta-analysis
      showed that tumour budding was significantly associated with lymph node
      metastasis (odds ratio=7.08, 95% CI=1.75-28.73), disease-free survival (hazard
      ratio=1.83, 95% CI=1.34-2.50) and overall survival (hazard ratio=1.88, 95%
      CI=1.25-2.82). CONCLUSIONS: Tumour budding is a simple and reliable prognostic
      marker for OSCC. Evaluation of tumour budding could facilitate personalised
      management of OSCC.

PMID- 29190644
TI  - Structural analysis of human glycoprotein butyrylcholinesterase using atomistic
      molecular dynamics: The importance of glycosylation site ASN241.
AB  - Human butyrylcholinesterase (BChE) is a glycoprotein capable of bioscavenging
      toxic compounds such as organophosphorus (OP) nerve agents. For commercial
      production of BChE, it is practical to synthesize BChE in non-human expression
      systems, such as plants or animals. However, the glycosylation profile in these
      systems is significantly different from the human glycosylation profile, which
      could result in changes in BChE's structure and function. From our investigation,
      we found that the glycan attached to ASN241 is both structurally and functionally
      important due to its close proximity to the BChE tetramerization domain and the
      active site gorge. To investigate the effects of populating glycosylation site
      ASN241, monomeric human BChE glycoforms were simulated with and without site
      ASN241 glycosylated. Our simulations indicate that the structure and function of
      human BChE are significantly affected by the absence of glycan 241.

PMID- 29190641
TI  - Intracardiac anatomical relationships and potential for streaming in double inlet
      left ventricles.
AB  - The aim of this study was to gain better understanding of the variable anatomical
      features of double inlet left ventricle hearts without cavopulmonary connection
      that would potentially facilitate favorable streaming. Thirty-nine post-mortem
      specimens of double inlet left ventricle without cavopulmonary connection were
      investigated. The focus was on anatomical characteristics that could influence
      the flow and separation of deoxygenated and oxygenated blood in the ventricles.
      Elements of interest were the ventriculoarterial connection, the spatial
      relationship of the ventricles, the position and size of the great arteries, the
      ventricular septal defect, the presence of relative outflow tract stenosis and
      the relationship of the inflow and outflow tracts. The most common anatomy was a
      discordant ventriculoarterial connection with an anatomically left-sided
      morphologically right ventricle (n = 12, 31%). When looking at the pulmonary
      trunk/aorta ratio, 21 (72%) hearts showed no pulmonary stenosis relative to the
      aorta. The ventricular septal defect created a relative subpulmonary or subaortic
      stenosis in 13 (41%) cases. Sixteen (41%) hearts had a parallel relationship of
      the inflow and outflow tracts, facilitating separation of deoxygenated and
      oxygenated blood streams. On the other end of the spectrum were 10 (25%) hearts
      with a perpendicular relationship, which might lead to maximum mixing of the
      blood streams. The relationship of the inflow and outflow tracts as well as the
      presence of (sub-) pulmonary stenosis might play a crucial role in the
      distribution of blood in double inlet left ventricle hearts. Additional in vivo
      studies will be necessary to confirm this postulation.

PMID- 29190639
TI  - Induction of colon and cervical cancer cell death by cinnamic acid derivatives is
      mediated through the inhibition of Histone Deacetylases (HDAC).
AB  - Recent studies from our group and many others have shown the ability of histone
      deacetylase (HDAC) inhibitors for retarding the growth of carcinomas of cervix,
      colon and rectum in vitro. A search for naturally occurring HDAC inhibitors
      continues due to the adverse effects associated with known HDAC inhibitors like
      SAHA and TSA. Therefore in the current study, naturally occurring cinnamic acids
      derivatives were screened for HDAC inhibitory effect using in silico docking
      method which identified cinnamic acids as potential candidates. Cinnamic acids
      (CA) are naturally occurring phenolic compounds known to exhibit anticancer
      properties. However, it is not clearly known whether the anticancer properties of
      CA derivatives are due to the inhibition of oncogenic HDACs, if so how the
      efficacy varies among various CA derivatives. Hence, the HDAC inhibitory
      potential of CA derivatives containing increasing number of hydroxylic groups or
      methoxy moieties was determined using Discovery Studio software and the most
      potent CA derivatives tested ex vivo (biochemical assay) as well as in vitro
      (using cell based assay). Among CA derivatives tested, dihydroxy cinnamic acid
      (DHCA, commonly known as caffeic acid) exhibited better interactions with HDAC2
      (compared to other isoforms) in silico and inhibited its activity ex vivo as well
      as in vitro. Targeted reduction of HDAC activity using DHCA induced death of
      cancer cells by (a) generating reactive oxygen species, (b) arresting cells in S
      and G2/M phases; and (c) induction of caspase-3 mediated apoptosis. In
      conclusion, we demonstrated that DHCA inhibited cancer cell growth by binding to
      HDAC followed by the induction of apoptosis.

PMID- 29190642
TI  - Measuring stigma affecting sex workers (SW) and men who have sex with men (MSM):
      A systematic review.
AB  - BACKGROUND: Stigma involves discrediting a person or group based on a perceived
      attribute, behaviour or reputation associated with them. Sex workers (SW) and men
      who have sex with men (MSM) are key populations who are often at increased risk
      for the acquisition and transmission of HIV and who are affected by stigma that
      can negatively impact their health and well-being. Although stigma was included
      as an indicator in the US National HIV/AIDS Strategic Plan and there have been
      consultations focused on adding a stigma indicator within PEPFAR and the Global
      Fund in relation to potentiating HIV risks among key populations, there remains
      limited consensus on the appropriate measurement of SW- or MSM-associated stigma.
      Consequently, this systematic review summarizes studies using quantitative,
      qualitative, or mixed methods approaches to measure stigma affecting sex workers
      and men who have sex with men. METHODS AND FINDINGS: This systematic review
      included English, French, and Spanish peer-reviewed research of any study design
      measuring SW- or MSM-associated stigma. Articles were published from January 1,
      2004 to March 26, 2014 in PsycINFO, PubMed, EMBASE, CINAHL Plus, Global Health,
      and World Health Organization Global Health Library Regional Indexes. Of the 541
      articles reviewed, the majority measured stigma toward MSM (over 97%), were
      conducted in North America, used quantitative methods, and focused on
      internalized stigma. CONCLUSIONS: With the inclusion of addressing stigma in
      several domestic and international HIV strategies, there is a need to ensure the
      use of validated metrics for stigma. The field to date has completed limited
      measurement of stigma affecting sex workers, and limited measurement of stigma
      affecting MSM outside of higher income settings. Moving forward requires a
      concerted effort integrating validated metrics of stigma into health-related
      surveys and programs for key populations.

PMID- 29190640
TI  - Perceptual integration rapidly activates dorsal visual pathway to guide local
      processing in early visual areas.
AB  - Rapidly grouping local elements into an organized object (i.e., perceptual
      integration) is a fundamental yet challenging task, especially in noisy contexts.
      Previous studies demonstrate that ventral visual pathway, which is widely known
      to mediate object recognition, engages in the process by conveying object-level
      information processed in high-level areas to modulate low-level sensory areas.
      Meanwhile, recent evidence suggests that the dorsal visual pathway, which is not
      typically attributable to object recognition, is also involved in the process.
      However, the underlying whole-brain fine spatiotemporal neuronal dynamics remains
      unknown. Here we used magnetoencephalography (MEG) recordings in combination with
      a temporal response function (TRF) approach to dissociate the time-resolved
      neuronal response that specifically tracks the perceptual grouping course. We
      demonstrate that perceptual integration initiates robust and rapid responses
      along the dorsal visual pathway in a reversed hierarchical manner, faster than
      the ventral pathway. Specifically, the anterior intraparietal sulcus (IPS)
      responds first (i.e., within 100 ms), followed by activities backpropagating
      along the dorsal pathway to early visual areas (EVAs). The IPS activity causally
      modulates the EVA response, even when the global form information is task
      irrelevant. The IPS-to-EVA response profile fails to appear when the global form
      could not be perceived. Our results support the crucial function of the dorsal
      visual pathway in perceptual integration, by quickly extracting a coarse global
      template (i.e., an initial object representation) within first 100 ms to guide
      subsequent local sensory processing so that the ambiguities in the visual inputs
      can be efficiently resolved.

PMID- 29190646
TI  - Risk factors for incidental durotomy during posterior open spine surgery for
      degenerative diseases in adults: A multicenter observational study.
AB  - Incidental durotomy (ID) is a common intraoperative complication of spine
      surgery. It can lead to persistent cerebrospinal fluid leakage, which may cause
      serious complications, including severe headache, pseudomeningocele formation,
      nerve root entrapment, and intracranial hemorrhage. As a result, it contributes
      to higher healthcare costs and poor patient outcomes. The purpose of this study
      was to clarify the independent risk factors that can cause ID during posterior
      open spine surgery for degenerative diseases in adults. We conducted a
      prospective multicenter study of adult patients who underwent posterior open
      spine surgery for degenerative diseases at 10 participating hospitals from July
      2010 to June 2013. A total of 4,652 consecutive patients were enrolled. We
      evaluated potential risk factors, including age, sex, body mass index, American
      Society of Anesthesiologists physical status classification, the presence of
      diabetes mellitus, the use of hemodialysis, smoking status, steroid intake,
      location of the surgery, type of operative procedure, and past surgical history
      in the operated area. A multivariate logistic regression analysis was performed
      to identify the risk factors associated with ID. The incidence of ID was 8.2%
      (380/4,652). Corrective vertebral osteotomy and revision surgery were identified
      as independent risk factors for ID, while cervical surgery and discectomy were
      identified as factors that independently protected against ID during posterior
      open spine surgery for degenerative diseases in adults. Therefore, we identified
      2 independent risk factors for and 2 protective factors against ID. These results
      may contribute to making surgeons aware of the risk factors for ID and can be
      used to counsel patients on the risks and complications associated with open
      spine surgery.

PMID- 29190649
TI  - Effects of Lactobacillus acidophilus on gut microbiota composition in broilers
      challenged with Clostridium perfringens.
AB  - This study shows the effects of dietary supplementation with Lactobacillus
      acidophilus on the gut microbiota of broiler chickens challenged with Clostridium
      perfringens infection during a 21-day period according to pyrosequencing of the
      16S ribosomal RNA gene. In a 2 * 2 factorial arrangement of treatments, 308 1-day
      old male Arbor Acres broiler chicks were analyzed for the effects of the
      probiotic (groups without or with L. acidophilus supplementation), pathogen
      challenge (groups without or with C. perfringens), and the effects of
      interaction. The infection decreased the number of Observed species, Chao1, and
      ACE of ileal microbiota and increased Chao1 of cecal microbiota of broilers,
      whereas L. acidophilus supplementation decreased the Shannon index of the ileal
      microbiota. Shannon index and Simpson indices were lower in the ileal microbiota
      than in the cecal microbiota. In the ileal microbiota, the control group had
      higher relative abundance of Lachnospiraceae and Ruminococcaceae in comparison
      with the other groups; however, the relative abundance of Gammaproteobacteria was
      significantly higher in the challenge group than in the other groups. C.
      perfringens infection tended to increase lactate concentration and
      decreasedconcentrations of formate, acetate and propionate in the ileum;
      decreased isobutyrate concentration; and tended to decrease isovalerate
      concentration in the cecum. Besides, L. acidophilus supplementation increased the
      concentration of lactate and butyrate and decreased concentrations of formate and
      propionate in the ileum, and increased concentrations of lactate and valerate in
      the cecum. In conclusion, C. perfringens infection and/or dietary supplementation
      with L. acidophilus modulated the relative abundance of some bacteria taxa, and
      the L. acidophilus supplementation helped to restore the microbial community
      disrupted by C. perfringens infection.

PMID- 29190647
TI  - The influence of inherited plumage colour morph on morphometric traits and
      breeding investment in zebra finches (Taeniopygia guttata).
AB  - Melanin-based plumage polymorphism occurs in many wild bird populations and has
      been linked to fitness variation in several species. These fitness differences
      often arise as a consequence of variation in traits such as behaviour, immune
      responsiveness, body size and reproductive investment. However, few studies have
      controlled for genetic differences between colour morphs that could potentially
      generate artefactual associations between plumage colouration and trait
      variation. Here, we used zebra finches (Taeniopygia guttata) as a model system in
      order to evaluate whether life-history traits such as adult body condition and
      reproductive investment could be influenced by plumage morph. To maximise any
      potential differences, we selected wild-type and white plumage morphs, which
      differ maximally in their extent of melanisation, while using a controlled three
      generation breeding design to homogenise the genetic background. We found that F2
      adults with white plumage colouration were on average lighter and had poorer body
      condition than wild-type F2 birds. However, they appeared to compensate for this
      by reproducing earlier and producing heavier eggs relative to their own body
      mass. Our study thus reveals differences in morphological and life history traits
      that could be relevant to fitness variation, although further studies will be
      required to evaluate fitness effects under natural conditions as well as to
      characterise any potential fitness costs of compensatory strategies in white
      zebra finches.

PMID- 29190645
TI  - CD105+-mesenchymal stem cells migrate into osteoarthritis joint: An animal model.
AB  - Mesenchymal stem cells are being the focus of connective tissue technology and
      regenerative medicine, presenting a good choice cell source for improving old and
      well recognized techniques of cartilage defect repair. For instance, the
      autologous chondrocyte transplantation using new concepts of regenerative
      medicine. The present study investigated the risk of xenogenicity of human
      synovial membrane-derived MSCs, injected into the monkeys using intravenous and
      intra-articular administration. The animal models used were adult monkeys Rhesus
      which had been injured into the left knee to create an Osteoarthritis (OA) animal
      model. CD105+-MSCs were injected twice into the OA monkeys with an interval of
      one week between them. The animals were euthanized one month after treatment.
      Immunohistochemistry analysis of different organs: spleen, heart, fat, liver,
      gut, pancreas, lung, skeletal muscle and kidney from the animals revealed that
      CD105+-MSCs migrated towards the injured knee joint. MSCs naive were found
      statistically significant increased in the injured knee in front of healthy one.
      CD105+-MSCs were negatives for CD68 and the area where CD105+-MSCs were found
      presented SDF-1 increased levels in front of healthy knee. We concluded that a
      characterized MSCs subset could be a safe alternative for cell therapy in clearly
      localized pathologies.

PMID- 29190648
TI  - Anterior chamber associated immune deviation used as a neuroprotective strategy
      in rats with spinal cord injury.
AB  - The inflammatory response is probably one of the main destructive events
      occurring after spinal cord injury (SCI). Its progression depends mostly on the
      autoimmune response developed against neural constituents. Therefore, modulation
      or inhibition of this self-reactive reaction could help to reduce tissue
      destruction. Anterior chamber associated immune deviation (ACAID) is a phenomenon
      that induces immune-tolerance to antigens injected into the eye's anterior
      chamber, provoking the reduction of such immune response. In the light of this
      notion, induction of ACAID to neural constituents could be used as a potential
      prophylactic therapy to promote neuroprotection. In order to evaluate this
      approach, three experiments were performed. In the first one, the capability to
      induce ACAID of the spinal cord extract (SCE) and the myelin basic protein (MBP)
      was evaluated. Using the delayed type hypersensibility assay (DTH) we
      demonstrated that both, SCE and MBP were capable of inducing ACAID. In the second
      experiment we evaluated the effect of SCE-induced ACAID on neurological and
      morphological recovery after SCI. In the results, there was a significant
      improvement of motor recovery, nociceptive hypersensitivity and motoneuron
      survival in rats with SCE-induced ACAID. Moreover, ACAID also up-regulated the
      expression of genes encoding for anti-inflammatory cytokines and FoxP3 but down
      regulated those for pro-inflamatory cytokines. Finally, in the third experiment,
      the effect of a more simple and practical strategy was evaluated: MBP-induced
      ACAID, we also found significant neurological and morphological outcomes. In the
      present study we demonstrate that the induction of ACAID against neural antigens
      in rats, promotes neuroprotection after SCI.

PMID- 29190643
TI  - Transcriptomic analysis of gene expression in mice treated with troxerutin.
AB  - Troxerutin, a semi-synthetic derivative of the natural bioflavanoid rutin, has
      been reported to possess many beneficial effects in human bodies, such as
      vasoprotection, immune support, anti-inflammation and anti-aging. However, the
      effects of troxerutin on genome-wide transcription in blood cells are still
      unknown. In order to find out effects of troxerutin on gene transcription, a high
      throughput RNA sequencing was employed to analysis differential gene expression
      in blood cells consisting of leucocytes, erythrocytes and platelets isolated from
      the mice received subcutaneous injection of troxerutin. Transcriptome analysis
      demonstrated that the expression of only fifteen genes was significantly changed
      by the treatment with troxerutin, among which 5 genes were up-regulated and 10
      genes were down-regulated. Bioinformatic analysis of the fifteen differentially
      expressed genes was made by utilizing the Gene Ontology (GO), and the
      differential expression induced by troxerutin was further evaluated by real-time
      quantitative PCR (Q-PCR).

PMID- 29190650
TI  - Reduced bone length, growth plate thickness, bone content, and IGF-I as a model
      for poor growth in the CFTR-deficient rat.
AB  - BACKGROUND: Reduced growth and osteopenia are common in individuals with cystic
      fibrosis (CF). Additionally, improved weight and height are associated with
      better lung function and overall health in the disease. Mechanisms for this
      reduction in growth are not understood. We utilized a new CFTR knockout rat to
      evaluate growth in young CF animals, via femur length, microarchitecture of bone
      and growth plate, as well as serum IGF-I concentrations. METHODS: Femur length
      was measured in wild-type (WT) and SD-CFTRtm1sage (Cftr-/-) rats, as a surrogate
      marker for growth. Quantitative bone parameters in Cftr-/- and WT rats were
      measured by micro computed tomography (micro-CT). Bone histomorphometry and
      cartilaginous growth plates were analyzed. Serum IGF-I concentrations were also
      compared. RESULTS: Femur length was reduced in both Cftr-/- male and female rats
      compared to WT. Multiple parameters of bone microarchitecture (of both trabecular
      and cortical bone) were adversely affected in Cftr-/- rats. There was a reduction
      in overall growth plate thichkness in both male and female Cftr-/- rats, as well
      as hypertrophic zone thickness and mean hypertrophic cell volume in male rats,
      indicating abnormal growth characteristics at the plate. Serum IGF-I
      concentrations were severely reduced in Cftr-/- rats compared to WT littermates.
      CONCLUSIONS: Despite absence of overt lung or pancreatic disease, reduced growth
      and bone content were readily detected in young Cftr-/- rats. Reduced size of the
      growth plate and decreased IGF-I concentrations suggest the mechanistic basis for
      this phenotype. These findings appear to be intrinsic to the CFTR deficient state
      and independent of significant clinical confounders, providing substantive
      evidence for the importance of CFTR on maintinaing normal bone growth.

PMID- 29190651
TI  - APOE allele frequencies in suspected non-amyloid pathophysiology (SNAP) and the
      prodromal stages of Alzheimer's Disease.
AB  - Biomarker definitions for preclinical Alzheimer's disease (AD) have identified
      individuals with neurodegeneration (ND+) without beta-amyloidosis (Abeta-) and
      labeled them with suspected non-AD pathophysiology (SNAP). We evaluated
      Apolipoprotein E (APOE) epsilon2 and epsilon4 allele frequencies across biomarker
      definitions-Abeta-/ND- (n = 268), Abeta+/ND- (n = 236), Abeta-/ND+ or SNAP (n =
      78), Abeta+/ND+ (n = 204)-hypothesizing that SNAP would have an APOE profile
      comparable to Abeta-/ND-. Using AD Neuroimaging Initiative data (n = 786, 72+/-7
      years, 48% female), amyloid status (Abeta+ or Abeta-) was defined by
      cerebrospinal fluid (CSF) Abeta-42 levels, and neurodegeneration status (ND+ or
      ND-) was defined by hippocampal volume from MRI. Binary logistic regression
      related biomarker status to APOE epsilon2 and epsilon4 allele carrier status,
      adjusting for age, sex, education, and cognitive diagnosis. Compared to the
      biomarker negative (Abeta-/ND-) participants, higher proportions of epsilon4 and
      lower proportions of epsilon2 carriers were observed among Abeta+/ND- (epsilon4:
      OR = 6.23, p<0.001; epsilon2: OR = 0.53, p = 0.03) and Abeta+/ND+ participants
      (epsilon4: OR = 12.07, p<0.001; epsilon2: OR = 0.29, p = 0.004). SNAP
      participants were statistically comparable to biomarker negative participants (p
      values>0.30). In supplemental analyses, comparable results were observed when
      coding SNAP using amyloid imaging and when using CSF tau levels. In contrast to
      APOE, a polygenic risk score for AD that excluded APOE did not show an
      association with amyloidosis or neurodegeneration (p-values>0.15), but did show
      an association with SNAP defined using CSF tau (beta = 0.004, p = 0.02). Thus, in
      a population with low levels of cerebrovascular disease and a lower prevalence of
      SNAP than the general population, APOE and known genetic drivers of AD do not
      appear to contribute to the neurodegeneration observed in SNAP. Additional work
      in population based samples is needed to better elucidate the genetic
      contributors to various etiological drivers of SNAP.

PMID- 29190652
TI  - Range-based volatility, expected stock returns, and the low volatility anomaly.
AB  - One of the foundations of financial economics is the idea that rational investors
      will discount stocks with more risk (volatility), which will result in a positive
      relation between risk and future returns. However, the empirical evidence is
      mixed when determining how volatility is related to future returns. In this
      paper, we examine this relation using a range-based measure of volatility, which
      is shown to be theoretically, numerically, and empirically superior to other
      measures of volatility. In a variety of tests, we find that range-based
      volatility is negatively associated with expected stock returns. These results
      are robust to time-series multifactor models as well as cross-sectional tests.
      Our findings contribute to the debate about the direction of the relationship
      between risk and return and confirm the presence of the low volatility anomaly,
      or the anomalous finding that low volatility stocks outperform high volatility
      stocks. In other tests, we find that the lower returns associated with range
      based volatility are driven by stocks with lottery-like characteristics.

PMID- 29190653
TI  - Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for
      imaging of unstable atherosclerotic plaques.
AB  - Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of
      atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel
      radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high
      selectivity and inhibitory potency. Inhibitory potencies of several halogenated
      analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl
      monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl
      monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with
      highest inhibitory potency and selectivity was radiolabelled with [123I],
      resulting in moderate radiochemical yield, and high radiochemical purity.
      Biodistribution studies in mice, revealed stabilization in blood 1 hour after
      intravenous bolus injection. Intravenous infusion of the radioligand and
      subsequent autoradiography of excised aortas showed tracer uptake in atheroprone
      mice. Distribution of the radioligand showed co-localization with MMP2/9
      immunohistochemical staining. In conclusion, we have developed a novel selective
      radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed
      tomography (SPECT) imaging that effectively targets atherosclerotic lesions in
      mice.

PMID- 29190654
TI  - Prenatal folic acid use associated with decreased risk of myelomeningocele: A
      case-control study offers further support for folic acid fortification in
      Bangladesh.
AB  - Neural tube defects contribute to severe morbidity and mortality in children and
      adults; however, they are largely preventable through maternal intake of folic
      acid before and during early pregnancy. We examined the association between
      maternal prenatal folic acid supplement intake and risk of myelomeningocele (a
      severe and common type of neural tube defect) in the offspring. We performed
      secondary analysis using data from a case-control study conducted at Dhaka
      Community Hospital, Bangladesh between April and November of 2013. Cases and
      controls included children with and without myelomeningocele, respectively, and
      their mothers. Cases were identified from local hospitals and rural health
      clinics served by Dhaka Community Hospital. Controls were selected from pregnancy
      registries located in the same region as the cases, and matched (1:1) to cases by
      age and sex. Myelomeningocele in the offspring was confirmed by a pediatrician
      with expertise in classifying neural tube defects. Maternal prenatal folic acid
      supplement intake was the main exposure of interest. We estimated crude and
      adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional
      logistic regression analysis. There were 53 pairs of matched cases and controls
      in our study. Overall, 51% of case mothers reported using folic acid supplements
      during pregnancy compared to 72% of control mothers (p = 0.03). Median plasma
      folate concentrations at the time of study visit were 2.79 ng/mL and 2.86 ng/mL
      among case and control mothers, respectively (p = 0.85). Maternal prenatal folic
      acid use significantly decreased the odds of myelomeningocele in the offspring
      (unadjusted OR = 0.42, 95% CI = 0.18-0.96). The association was slightly
      attenuated after adjusting for maternal age at the time of pregnancy (adjusted OR
      = 0.43, 95% CI = 0.18-1.02). Our study confirms the protective association
      between maternal prenatal folic acid supplement use and myelomeningocele among
      children born in Bangladesh. Our findings point to an overall low folic acid
      supplement use and low plasma folate concentrations among women of reproductive
      age in Bangladesh. Mandatory fortification of staple foods with folic acid can
      address low folate status among women of child-bearing age, and prevent child
      morbidity and mortality associated with myelomeningocele in Bangladesh.

PMID- 29190655
TI  - The effects of a culturally-tailored campaign to increase blood donation
      knowledge, attitudes and intentions among African migrants in two Australian
      States: Victoria and South Australia.
AB  - Research suggests that African migrants are often positively predisposed towards
      blood donation, but are under-represented in participation. A culturally-tailored
      intervention targeting the African migrant community in Australia was developed
      and implemented, to enhance knowledge about blood donation, improve attitudes
      towards donating, increase intentions to donate blood, and increase the number of
      new African donors in Australia. Four weeks after a targeted campaign, a survey
      evaluation process commenced, administered face-to-face by bilingual interviewers
      from the African community in Melbourne and Adelaide, Australia (community
      survey). The questionnaires covered demographics, campaign awareness, blood
      donation knowledge and intentions, medical mistrust and perceived discrimination,
      and were analysed to evaluate changes in knowledge and intention. Sixty-two
      percent of survey participants (n = 454) reported being aware of the campaign.
      With increasing campaign awareness, there was a 0.28 increase in knowledge score
      (p = .005); previous blood donation was also associated with an increased blood
      donation knowledge score. Blood donation intention scores were not associated
      with campaign awareness (p = 0.272), but were associated with previous blood
      donation behaviour and a positive blood donation attitude score. More positive
      scores on the blood donation attitude measure were associated with increasing
      blood donation intentions, self-efficacy and campaign awareness (score increases
      of 0.27, 0.30 and 0.04, respectively, all p<0.05). Data were collected on the
      ethnicity of new blood donors in six blood collection centres before and after
      the intervention, and independent of the intervention evaluation survey. These
      data were also used to assess behavioural changes and the proportions of donors
      from different countries before and after the survey. There was no difference in
      the number of new African migrant donors, before and after the intervention. The
      culturally-relevant marketing campaign was associated with improved blood
      donation knowledge and attitudes, but there was no short-term change in blood
      donation intentions or the number of African donors.

PMID- 29190656
TI  - MRI for the assessment of malignancy in BI-RADS 4 mammographic
      microcalcifications.
AB  - PURPOSE: Assess the performance of breast MRI to diagnose breast cancer in BI
      RADS 4 microcalcifications detected by mammography. MATERIALS AND METHODS: This
      retrospective, IRB-approved study included 248 consecutive contrast-enhanced
      breast MRI (1.5T, protocol in accordance with EUSOBI recommendations) performed
      to further diagnose BI-RADS 4 microcalcifications detected at mammography during
      a 3-year period. Standard of reference had to be established by histopathology.
      Routine consensus reading results by two radiologists were dichotomized as
      positive or negative and compared with the reference standard (benign vs
      malignant) to calculate diagnostic parameters. RESULTS: There were 107 malignant
      and 141 benign microcalcifications. Malignancy rates were 18.3% (23/126 BI-RADS
      4a), 41.7% (25/60 BI-RADS 4b) and 95% (59/62 BI-RADS 4c). There were 103 true
      positive, 116 true-negative, 25 false-positive, and 4 false-negative (one
      invasive cancer, three DCIS; 2 BI-RADS 4c, 1 BI-RADS 4b on mammography) breast
      MRI findings, effecting a sensitivity, specificity, PPV, and NPV of 96.3% (95%-CI
      90.7-99.0%), 82.3% (95%-CI 75.0-88.2%), 80.5% (95%-CI 72.5-87.0%) and 96.7% (95%
      CI 91.7-99.1%), respectively. CONCLUSION: MRI is an accurate tool to further
      diagnose BI-RADS 4a and 4b microcalcifications and may be helpful to avoid
      unnecessary biopsies in BI-RADS 4a and 4b lesions. BI-RADS 4c microcalcifications
      should be biopsied irrespective of MRI findings.

PMID- 29190657
TI  - Tree seedlings respond to both light and soil nutrients in a Patagonian evergreen
      deciduous forest.
AB  - Seedlings of co-occurring species vary in their response to resource availability
      and this has implications for the conservation and management of forests.
      Differential shade-tolerance is thought to influence seedling performance in
      mixed Nothofagus betuloides-Nothofagus pumilio forests of Patagonia. However,
      these species also vary in their soil nutrient requirements. To determine the
      effects of light and soil nutrient resources on small seedlings we examined
      responses to an experimental reduction in canopy tree root competition through
      root trenching and restricting soil nutrient depletion through the addition of
      fertilizer. To understand the effect of light these treatments were undertaken in
      small canopy gaps and nearby beneath undisturbed canopy with lower light levels.
      Seedling diameter growth was greater for N. pumilio and height growth was greater
      for N. betuloides. Overall, diameter and height growth were greater in canopy
      gaps than beneath undisturbed canopy. Such growths were also greater with
      fertilizer and root trenching treatments, even beneath undisturbed canopy.
      Seedling survival was lower under such treatments, potentially reflecting
      thinning facilitated by resource induced growth. Finally, above-ground biomass
      did not vary among species although the less shade tolerant N. pumilio had higher
      below-ground biomass and root to shoot biomass ratio than the more shade tolerant
      N. betuloides. Above- and below-ground biomass were higher in canopy gaps so that
      the root to shoot biomass ratio was similar to that beneath undisturbed canopy.
      Above-ground biomass was also higher with fertilizer and root trenching
      treatments and that lowered the root to shoot biomass ratio. Restricting soil
      nutrient depletion allowed seedlings of both species to focus their responses
      above-ground. Our results support a view that soil nutrient resources, as well as
      the more commonly studied light resources, are important to seedlings of
      Nothofagus species occurring on infertile soils.

PMID- 29190658
TI  - Screening tools to identify patients with complex health needs at risk of high
      use of health care services: A scoping review.
AB  - BACKGROUND: Many people with chronic conditions have complex health needs often
      due to multiple chronic conditions, psychiatric comorbidities, psychosocial
      issues, or a combination of these factors. They are at high risk of frequent use
      of healthcare services. To offer these patients interventions adapted to their
      needs, it is crucial to be able to identify them early. OBJECTIVE: The aim of
      this study was to find all existing screening tools that identify patients with
      complex health needs at risk of frequent use of healthcare services, and to
      highlight their principal characteristics. Our purpose was to find a short, valid
      screening tool to identify adult patients of all ages. METHODS: A scoping review
      was performed on articles published between 1985 and July 2016, retrieved through
      a comprehensive search of the Scopus and CINAHL databases, following the
      methodological framework developed by Arksey and O'Malley (2005), and completed
      by Levac et al. (2010). RESULTS: Of the 3,818 articles identified, 30 were
      included, presenting 14 different screening tools. Seven tools were self
      reported. Five targeted adult patients, and nine geriatric patients. Two tools
      were designed for specific populations. Four can be completed in 15 minutes or
      less. Most screening tools target elderly persons. The INTERMED self-assessment
      (IM-SA) targets adults of all ages and can be completed in less than 15 minutes.
      CONCLUSION: Future research could evaluate its usefulness as a screening tool for
      identifying patients with complex needs at risk of becoming high users of
      healthcare services.

PMID- 29190659
TI  - A digital memories based user authentication scheme with privacy preservation.
AB  - The traditional username/password or PIN based authentication scheme, which still
      remains the most popular form of authentication, has been proved insecure,
      unmemorable and vulnerable to guessing, dictionary attack, key-logger, shoulder
      surfing and social engineering. Based on this, a large number of new alternative
      methods have recently been proposed. However, most of them rely on users being
      able to accurately recall complex and unmemorable information or using extra
      hardware (such as a USB Key), which makes authentication more difficult and
      confusing. In this paper, we propose a Digital Memories based user authentication
      scheme adopting homomorphic encryption and a public key encryption design which
      can protect users' privacy effectively, prevent tracking and provide multi-level
      security in an Internet & IoT environment. Also, we prove the superior
      reliability and security of our scheme compared to other schemes and present a
      performance analysis and promising evaluation results.

PMID- 29190660
TI  - Actionable mutations in canine hemangiosarcoma.
AB  - BACKGROUND: Angiosarcomas (AS) are rare in humans, but they are a deadly subtype
      of soft tissue sarcoma. Discovery sequencing in AS, especially the visceral form,
      is hampered by the rarity of cases. Most diagnostic material exists as archival
      formalin fixed, paraffin embedded tissue which serves as a poor source of high
      quality DNA for genome-wide sequencing. We approached this problem through
      comparative genomics. We hypothesized that exome sequencing a histologically
      similar tumor, hemangiosarcoma (HSA), that occurs in approximately 50,000 dogs
      per year, may lead to the identification of potential oncogenic drivers and
      druggable targets that could also occur in angiosarcoma. METHODS: Splenic
      hemangiosarcomas are common in dogs, which allowed us to collect a cohort of
      archived matched tumor and normal tissue samples suitable for whole exome
      sequencing. Mapping of the reads to the latest canine reference genome (Canfam3)
      demonstrated that >99% of the targeted exomal regions were covered, with >80% at
      20X coverage and >90% at 10X coverage. RESULTS AND CONCLUSIONS: Sequence analysis
      of 20 samples identified somatic mutations in PIK3CA, TP53, PTEN, and PLCG1, all
      of which correspond to well-known tumor drivers in human cancer, in more than
      half of the cases. In one case, we identified a mutation in PLCG1 identical to a
      mutation observed previously in this gene in human visceral AS. Activating PIK3CA
      mutations present novel therapeutic targets, and clinical trials of targeted
      inhibitors are underway in human cancers. Our results lay a foundation for
      similar clinical trials in canine HSA, enabling a precision medicine approach to
      this disease.

PMID- 29190661
TI  - Physiological effects of a novel artificially synthesized antimalarial cyclic
      peptide: Mahafacyclin B.
AB  - Mahafacyclin B is a cyclic peptide isolated from the latex of Jatropha
      mahafalensis and is an antimalarial agent. However, the physiological effects of
      mahafacyclin B in mammalian cells are not known. Here, we assessed the growth,
      morphology, and alterations in the transcriptome of CHO-K1 cells exposed to
      mahafacyclin B (0-22 MUM). Mahafacyclin B at 2.2 MUM did not affect the
      proliferation or death of CHO-K1 cells. Mahafacyclin B was not toxic to mammalian
      cells at 2.2 MUM, which represents a normal physiological concentration at which
      mahafacyclin B retains its antimalarial properties. Interestingly, mahafacyclin B
      altered the size and morphology of CHO-K1 cells. Comparative transcriptomics
      revealed that mahafacyclin B modulated the expression of a specific subset of
      genes.

PMID- 29190662
TI  - Using systems science to understand the determinants of inequities in healthy
      eating.
AB  - INTRODUCTION: Systems thinking has emerged in recent years as a promising
      approach to understanding and acting on the prevention and amelioration of non
      communicable disease. However, the evidence on inequities in non-communicable
      diseases and their risks factors, particularly diet, has not been examined from a
      systems perspective. We report on an approach to developing a system oriented
      policy actor perspective on the multiple causes of inequities in healthy eating.
      METHODS: Collaborative conceptual modelling workshops were held in 2015 with an
      expert group of representatives from government, non-government health
      organisations and academia in Australia. The expert group built a systems model
      using a system dynamics theoretical perspective. The model developed from
      individual mind maps to pair blended maps, before being finalised as a causal
      loop diagram. RESULTS: The work of the expert stakeholders generated a
      comprehensive causal loop diagram of the determinants of inequity in healthy
      eating (the HE2 Diagram). This complex dynamic system has seven sub-systems: (1)
      food supply and environment; (2) transport; (3) housing and the built
      environment; (4) employment; (5) social protection; (6) health literacy; and (7)
      food preferences. DISCUSSION: The HE2 causal loop diagram illustrates the
      complexity of determinants of inequities in healthy eating. This approach, both
      the process of construction and the final visualisation, can provide the basis
      for planning the prevention and amelioration of inequities in healthy eating that
      engages with multiple levels of causes and existing policies and programs.

PMID- 29190663
TI  - Self-microemulsifying drug delivery system and nanoemulsion for enhancing aqueous
      miscibility of Alpinia galanga oil.
AB  - Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility
      limits its application particularly in aquatic animals. AGO has powerful activity
      on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows
      severe side effects on fish. The present study explores the development of self
      microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver
      AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams
      were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were
      developed by means of high-energy emulsification. The mean droplet size of the
      best SMEDDS-AGO was 82 +/- 0.5 nm whereas that of NE-AGO was 48 +/- 1.6 nm. The
      anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio)
      was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found
      that the time of induction the fish to reach the surgical stage of anesthesia was
      dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and
      EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This
      side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In
      conclusion, SMEDDS and NE are promising delivery systems for AGO.

PMID- 29190664
TI  - A systematic review of zoonotic enteric parasitic diseases among nomadic and
      pastoral people.
AB  - INTRODUCTION: Zoonotic enteric parasites are ubiquitous and remain a public
      health threat to humans due to our close relationship with domestic animals and
      wildlife, inadequate water, sanitation, and hygiene practices and diet. While
      most communities are now sedentary, nomadic and pastoral populations still exist
      and experience unique exposure risks for acquiring zoonotic enteric parasites.
      Through this systematic review we sought to summarize published research
      regarding pathogens present in nomadic populations and to identify the risk
      factors for their infection. METHODS: Using systematic review guidelines set
      forth by PRISMA, research articles were identified, screened and summarized based
      on exclusion criteria for the documented presence of zoonotic enteric parasites
      within nomadic or pastoral human populations. A total of 54 articles published
      between 1956 and 2016 were reviewed to determine the pathogens and exposure risks
      associated with the global transhumance lifestyle. RESULTS: The included articles
      reported more than twenty different zoonotic enteric parasite species and
      illustrated several risk factors for nomadic and pastoralist populations to
      acquire infection including; a) animal contact, b) food preparation and diet, and
      c) household characteristics. The most common parasite studied was Echinococcosis
      spp. and contact with dogs was recognized as a leading risk factor for zoonotic
      enteric parasites followed by contact with livestock and/or wildlife, water,
      sanitation, and hygiene barriers, home slaughter of animals, environmental water
      exposures, household member age and sex, and consumption of unwashed produce or
      raw, unprocessed, or undercooked milk or meat. CONCLUSION: Nomadic and pastoral
      communities are at risk of infection with a variety of zoonotic enteric parasites
      due to their living environment, cultural and dietary traditions, and close
      relationship to animals. Global health efforts aimed at reducing the transmission
      of these animal-to-human pathogens must incorporate a One Health approach to
      support water, sanitation, and hygiene development, provide education on safe
      food handling and preparation, and improve the health of domestic animals
      associated with these groups, particularly dogs.

PMID- 29190665
TI  - Distinctness of Brazilian common bean cultivars with carioca and black grain by
      means of morphoagronomic and molecular descriptors.
AB  - Common bean (Phaseolus vulgaris L.) is one of the most important legumes for
      human consumption and is a staple food in the diet of the population of some
      countries of Latin America, Africa and Asia. The distinction between cultivars is
      based predominantly on morphological descriptors, which proved inefficient for
      the differentiation of some cultivars. This study had the objective of
      describing, distinguishing and evaluating the agronomic potential of 39 common
      bean cultivars of the carioca and black grain groups registered for cultivation
      in Brazil, based on 49 morphoagronomic descriptors and microsatellite (simple
      sequence repeat -SSR) markers. The morphoagronomic traits of each commercial
      group were characterized in four environments. Thirty-seven SSR markers were used
      for the molecular description. The morphological data, analyzed by the Shanonon
      Weaver index, detected low variability among cultivars for qualitative data. On
      the other hand, the estimates of variance analysis, relative importance of the
      traits and hierarchical grouping analysis applied to the quantitative variables
      showed that the descriptors related to plant morphology were the most important
      for the carioca group, and those related to seed morphology were determining for
      the black group. The genetic parameters estimated for SSR markers by hierarchical
      and Bayesian cluster analysis identified 116 alleles, with 33 and 30 polymorphic
      loci and 24 and 22 private alleles for the carioca and black groups,
      respectively. The combined use of morphoagronomic and molecular descriptors
      improves the distinguishability of cultivars, contributing in a more efficient
      way to breeding and to the protection of cultivars.

PMID- 29190666
TI  - Movement to outpatient hysterectomy for benign indications in the United States,
      2008-2014.
AB  - INTRODUCTION: The past decade has witnessed adoption of conservative gynecologic
      treatments, including minimally invasive surgery (MIS), alongside steady declines
      in inpatient hysterectomies. It remains unclear what factors have contributed to
      trends in outpatient benign hysterectomy (BH), as well as whether these trends
      exacerbate disparities. MATERIALS AND METHODS: Retrospective cohort of 527,964
      women >=18 years old who underwent BH from 2008 to 2014. BH surgical approaches
      included: open/abdominal hysterectomy (AH), vaginal hysterectomy (VH),
      laparoscopic hysterectomy (LH), and robotic-assisted hysterectomy (RH). Quarterly
      frequencies were calculated by care setting and surgical approach. We used
      multilevel logistic regression (MLR) using the most recent year of data (2014) to
      examine the influence of patient-, physician-, and hospital-level preoperative
      factors and surgical approaches on outpatient migration. RESULTS: From 2008-2014,
      surgical approaches for LH and RH increased, which coincided with decreases in VH
      and AH. Overall, a 44.2% shift was observed from inpatient to outpatient settings
      (P<0.0001). Among all outpatient visits MIS increased, particularly for RH (3.6%
      to 41.07%). We observed increases in the proportion of non-Hispanic Black and
      Medicaid patients who obtained MIS in 2014 vs. 2008 (P<0.001). Surgical approach
      (51.8%) and physician outpatient MIS experience (19.9%) had the greatest
      influence on predicting outpatient BH. Compared with LH, RH was associated with
      statistically significantly higher likelihood of outpatient BH overall (OR 1.23;
      95% CI, 1.16-1.31), as well as in sub-analyses of more complex cases and
      hospitals that performed >=1 RH (P<0.05). CONCLUSION: From 2008-2014, rates of LH
      and RH significantly increased. A significant shift from inpatient to outpatient
      setting was observed. These findings suggest that RH may facilitate the shift to
      outpatient BH, particularly for patients with complexities. The adoption of MIS
      in outpatient settings may improve access to disadvantaged patient groups.

PMID- 29190667
TI  - Hospital admissions for skin infections among Western Australian children and
      adolescents from 1996 to 2012.
AB  - The objective of this study was to describe the occurrence of skin infection
      associated hospitalizations in children born in Western Australia (WA). We
      conducted a retrospective cohort study of all children born in WA between 1996
      and 2012 (n = 469,589). Of these, 31,348 (6.7%) were Aboriginal and 240,237
      (51.2%) were boys. We report the annual age-specific hospital admission rates by
      geographical location and diagnostic category. We applied log-linear regression
      modelling to analyse changes in temporal trends of hospitalizations.
      Hospitalization rates for skin infections in Aboriginal children (31.7/1000 child
      years; 95% confidence interval [CI] 31.0-32.4) were 15.0 times higher (95% CI
      14.5-15.5; P<0.001) than those of non-Aboriginal children (2.1/1000 child-years;
      95% CI 2.0-2.1). Most admissions in Aboriginal children were due to abscess,
      cellulitis and scabies (84.3%), while impetigo and pyoderma were the predominant
      causes in non-Aboriginal children (97.7%). Admissions declined with age, with the
      highest rates for all skin infections observed in infants. Admissions increased
      with remoteness. Multiple admissions were more common in Aboriginal children.
      Excess admissions in Aboriginal children were observed during the wet season in
      the Kimberley and during summer in metropolitan areas. Our study findings show
      that skin infections are a significant cause of severe disease, requiring
      hospitalization in Western Australian children, with Aboriginal children at a
      particularly high risk. Improved community-level prevention of skin infections
      and the provision of effective primary care are crucial in reducing the burden of
      skin infection associated hospitalizations. The contribution of sociodemographic
      and environmental risk factors warrant further investigation.

PMID- 29190669
TI  - The performance of tranchet blows at the Late Middle Paleolithic site of Grotte
      de la Verpilliere I (Saone-et-Loire, France).
AB  - This paper focuses on the technological characteristics of Keilmesser with a
      lateral tranchet blow modification on the cutting edge. It examines the
      underlying technological production of these bifacial objects: this implies the
      evaluation of their working stage succession, as well as produced forms necessary
      for the execution of tranchet blow performance. Furthermore, it offers a techno
      morphological description of these enigmatic tools. The Keilmesser with tranchet
      blow and corresponding blanks of tranchet blows from Grotte de la Verpilliere I
      in Germolles (Saone-et-Loire, France) are used as case study. The collection of
      Keilmesser with tranchet blow and corresponding blanks of tranchet blow has been
      massively expanded with new fieldwork and the review of ancient assemblages. The
      majority of the pieces were made on blanks from local raw material. The
      evaluation of the underlying production concept shows that a Keilmesser with
      tranchet blow, regardless of the wide range of morphologies and matrix size,
      always consists of specific parts that are necessary for the production sequence
      and the assumed function. The production of these pieces follows highly specific
      working stages, some of which can be interchanged in sequence. However, it is
      always the goal to obtain a low-angled cutting edge. The performance of a
      tranchet blow is not only an integral part of production, but it is rather the
      aim of the entire production.

PMID- 29190668
TI  - Dual expression of immunoreactive estrogen receptor beta and p53 is a potential
      predictor of regional lymph node metastasis and postoperative recurrence in
      endometrial endometrioid carcinoma.
AB  - Although histological grade and muscular invasion are related to the malignant
      behaviors of endometrial endometrioid carcinoma, lymphatic and/or distant
      metastases are unexpectedly encountered, even in patients in the low-risk group.
      To re-evaluate additional reliable parameters to predict the risk of progression,
      we examined the immunohistochemical expression profiles of p53 and estrogen
      receptor (ER) beta proteins. Patients with endometrial endometrioid carcinoma who
      underwent surgical treatment at our hospital (n = 154) were recruited to this
      study, and the significance of the relationships between the incidence of
      regional lymph node metastasis and/or postoperative recurrence and clinical or
      experimental parameters was evaluated. By multivariate analysis, we found that
      histological grades, detection of immunoreactive p53 (positive rates more than
      10%, p53-stained), and high expression of ERbeta (high-ERbeta) were independently
      associated with metastasis and/or recurrence. Among these parameters, the
      sensitivity and negative predictive values of high-ERbeta were very high (up to
      100%). In the population with high-ERbeta, the positive rates of metastasis
      and/or recurrence were 61.1% in the p53-stained group and 21.9% in the p53-non
      stained (negative) group. Furthermore, the positive rate in the group showing
      myometrial invasion of more than 1/2 and showing both p53-stained and high-ERbeta
      was 80%. The disease-free survival of patients who were double-positive for p53
      stained and high-ERbeta was significantly shorter than that in other patients. In
      summary, our findings showed that increases in ERbeta and p53 immunoreactivity
      were significantly correlated with the incidence of metastasis and/or recurrence
      in endometrial endometrioid carcinoma, suggesting that double-positivity for p53
      stained and high-ERbeta may provide a promising clinical indicator to predict the
      risk of progression.

PMID- 29190670
TI  - Quantification of HBsAg to predict low levels and seroclearance in HBeAg-negative
      patients receiving nucleos(t)ide analogues.
AB  - BACKGROUND: HBeAg-negative chronic hepatitis B patients require long-term
      nucleos(t)ide analogues(NAs) because loss of surface antigen (HBsAg) is unusual.
      Low quantitative HBsAg (qHBsAg) levels can identify patients with higher
      probability of seroclearance. The aim of our study was to evaluate qHBsAg in
      HBeAg-negative patients receiving NAs to predict a reduction of HBsAg levels and
      seroclearance. METHODS: Retrospective analysis of qHBsAg in HBeAg-negative
      patients before and at years 1, 3, 5, 8 and over of NAs treatment. RESULTS: From
      1999 to 2015, HBsAg was quantified in 358 serum samples from 95 HBeAg-negative
      patients. Low qHBsAg (<120 IU/mL) was identified at baseline or during follow-up
      in 14% of patients and HBsAg loss in 4%. No baseline variables predicted
      seroclearance and only treatment duration predicted low qHBsAg. The annual
      decline of qHBsAg was -0.102 log IU/mL and the median time to HBsAg loss was 6.04
      years. The decline was greater in patients achieving low HBsAg levels (-0.257)
      than in those who did not (-0.057)(p<0.001). The diagnostic accuracy (ROC curve,
      95%CI) of qHBsAg delta at year 3 was 0.89 (0.81-0.97), with cut-off >0.3 log
      IU/mL showing a positive and negative predictive value of 42% and 100% to
      identify patients achieving low levels of HBsAg. CONCLUSIONS: Reduction of qHBsAg
      is slow in HBeAg-negative patients receiving NAs, although low levels or faster
      qHBsAg decline may occur in 14%. A qHBsAg reduction >0.3 log IU/mL at year 3 can
      identify patients with a higher probability of achieving low levels and HBsAg
      seroclearance.

PMID- 29190671
TI  - malERA: An updated research agenda for insecticide and drug resistance in malaria
      elimination and eradication.
AB  - Resistance to first-line treatments for Plasmodium falciparum malaria and the
      insecticides used for Anopheles vector control are threatening malaria
      elimination efforts. Suboptimal responses to drugs and insecticides are both
      spreading geographically and emerging independently and are being seen at
      increasing intensities. Whilst resistance is unavoidable, its effects can be
      mitigated through resistance management practices, such as exposing the parasite
      or vector to more than one selective agent. Resistance contributed to the failure
      of the 20th century Global Malaria Eradication Programme, and yet the global
      response to this issue continues to be slow and poorly coordinated-too often, too
      little, too late. The Malaria Eradication Research Agenda (malERA) Refresh
      process convened a panel on resistance of both insecticides and antimalarial
      drugs. This paper outlines developments in the field over the past 5 years,
      highlights gaps in knowledge, and proposes a research agenda focused on managing
      resistance. A deeper understanding of the complex biological processes involved
      and how resistance is selected is needed, together with evidence of its public
      health impact. Resistance management will require improved use of entomological
      and parasitological data in decision making, and optimisation of the useful life
      of new and existing products through careful implementation, combination, and
      evaluation. A proactive, collaborative approach is needed from basic science and
      the development of new tools to programme and policy interventions that will
      ensure that the armamentarium of drugs and insecticides is sufficient to deal
      with the challenges of malaria control and its elimination.

PMID- 29190674
TI  - A Bayesian view of murine seminal cytokine networks.
AB  - It has long been established that active agents in seminal fluid are key to
      initiating and coordinating mating-induced immunomodulation. This is in part
      governed by the actions of a network of cytokine interactions which, to date,
      remain largely undefined, and whose interspecific evolutionary conservation is
      unknown. This study applied Bayesian methods to illustrate the interrelationships
      between seminal profiles of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5,
      IL-6, IL-9, IL-10, IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony
      stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM
      CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte
      chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1) alpha,
      MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES),
      tumour necrosis factor (TNF)-alpha, leptin, inducible protein (IP)-10 and
      vascular endothelial growth factor (VEGF) in a rat model. IL-2, IL-9, IL-12
      (p70), IL-13, IL-18, eotaxin, IFN-gamma, IP-10, KC, leptin, MCP-1, MIP-1alpha and
      TNF-alpha were significantly higher in serum, whilst IL-1beta, IL-5, IL-6, IL-10,
      IL-17, G-CSF and GM-CSF were significantly higher in seminal fluid. When compared
      to mouse profiles, only G-CSF was present at significantly higher levels in the
      seminal fluid in both species. Bayesian modelling highlighted key shared features
      across mouse and rat networks, namely TNF-alpha as the terminal node in both
      serum and seminal plasma, and MCP-1 as a central coordinator of seminal cytokine
      networks through the intermediary of KC and RANTES. These findings reveal a
      marked interspecific conservation of seminal cytokine networks.

PMID- 29190673
TI  - Campylobacter jejuni transcriptome changes during loss of culturability in water.
AB  - BACKGROUND: Water serves as a potential reservoir for Campylobacter, the leading
      cause of bacterial gastroenteritis in humans. However, little is understood about
      the mechanisms underlying variations in survival characteristics between
      different strains of C. jejuni in natural environments, including water. RESULTS:
      We identified three Campylobacter jejuni strains that exhibited variability in
      their ability to retain culturability after suspension in tap water at two
      different temperatures (4 degrees C and 25 degrees C). Of the three, strains C.
      jejuni M1 exhibited the most rapid loss of culturability whilst retaining
      viability. Using RNAseq transcriptomics, we characterised C. jejuni M1 gene
      expression in response to suspension in water by analyzing bacterial suspensions
      recovered immediately after introduction into water (Time 0), and from two
      sampling time/temperature combinations where considerable loss of culturability
      was evident, namely (i) after 24 h at 25 degrees C, and (ii) after 72 h at 4
      degrees C. Transcript data were compared with a culture-grown control. Some gene
      expression characteristics were shared amongst the three populations recovered
      from water, with more genes being up-regulated than down. Many of the up
      regulated genes were identified in the Time 0 sample, whereas the majority of
      down-regulated genes occurred in the 25 degrees C (24 h) sample. CONCLUSIONS:
      Variations in expression were found amongst genes associated with oxygen
      tolerance, starvation and osmotic stress. However, we also found upregulation of
      flagellar assembly genes, accompanied by down-regulation of genes involved in
      chemotaxis. Our data also suggested a switch from secretion via the sec system to
      via the tat system, and that the quorum sensing gene luxS may be implicated in
      the survival of strain M1 in water. Variations in gene expression also occurred
      in accessory genome regions. Our data suggest that despite the loss of
      culturability, C. jejuni M1 remains viable and adapts via specific changes in
      gene expression.

PMID- 29190672
TI  - First-in-human phase I study of ISTH0036, an antisense oligonucleotide
      selectively targeting transforming growth factor beta 2 (TGF-beta2), in subjects
      with open-angle glaucoma undergoing glaucoma filtration surgery.
AB  - PURPOSE: To evaluate the safety and tolerability of intravitreal ISTH0036, an
      antisense oligonucleotide selectively targeting transforming growth factor beta 2
      (TGF-beta2), in patients with primary open angle glaucoma (POAG) undergoing
      trabeculectomy (TE; glaucoma filtration surgery). METHODS: In this prospective
      phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received
      a single intravitreal injection of ISTH0036 at the end of surgery in escalating
      total doses of 6.75 MUg, 22.5 MUg, 67.5 MUg or 225 MUg, resulting in calculated
      intraocular ISTH0036 concentrations in the vitreous humor of approximately 0.3
      MUM, 1 MUM, 3 MUM or 10 MUM after injection, respectively. Outcomes assessed
      included: type and frequency of adverse events (AEs), intraocular pressure (IOP),
      numbers of interventions post trabeculectomy, bleb survival, visual acuity,
      visual field, electroretinogram (ERG), slit lamp biomicroscopy and optic disc
      assessment. RESULTS: In total, 12 patients were treated in the 4 dose groups.
      Main ocular AEs observed were corneal erosion, corneal epithelium defect, or too
      high or too low IOP, among others. No AE was reported to be related to ISTH0036.
      All other safety-related analyses did not reveal any toxicities of concern,
      either. The mean medicated preoperative IOP at decision time-point for surgery
      was 27.3 mmHg +/- 12.6 mmHg (SD). Mean IOP (+/-SD) for dose levels 1, 2, 3, and 4
      were at Day 43 9.8 mmHg +/- 1.0 mmHg, 11.3 mmHg +/- 6.7 mmHg, 5.5 mmHg +/- 3.0
      mmHg and 7.5 mmHg +/- 2.3 mmHg SD; and at Day 85 9.7 mmHg +/- 3.3 mmHg, 14.2 mmHg
      +/- 6.5 mmHg, 5.8 mmHg +/- 1.8 mmHg and 7.8 mmHg +/- 0.6 mmHg, respectively. In
      contrast to IOP values for dose levels 1 and 2, IOP values for dose levels 3 and
      4 persistently remained below 10 mmHg throughout the observation period.
      CONCLUSION: This first-in-human trial demonstrates that intravitreal injection of
      ISTH0036 at the end of TE is safe. Regarding IOP control, single-dose ISTH0036
      administration of 67.5 MUg or 225 MUg at the time of TE resulted in IOP values
      persistently < 10 mmHg over the three month postoperative observation period.

PMID- 29190675
TI  - In patients with suspected acute stroke, CT perfusion-based cerebral blood flow
      maps cannot substitute for DWI in measuring the ischemic core.
AB  - BACKGROUND: Neuroimaging may guide acute stroke treatment by measuring the volume
      of brain tissue in the irreversibly injured "ischemic core." The most widely
      accepted core volume measurement technique is diffusion-weighted MRI (DWI).
      However, some claim that measuring regional cerebral blood flow (CBF) with CT
      perfusion imaging (CTP), and labeling tissue below some threshold as the core,
      provides equivalent estimates. We tested whether any threshold allows reliable
      substitution of CBF for DWI. METHODS: 58 patients with suspected stroke underwent
      DWI and CTP within six hours of symptom onset. A neuroradiologist outlined DWI
      lesions. In CBF maps, core pixels were defined by thresholds ranging from 0%-100%
      of normal, in 1% increments. Replicating prior studies, we used receiver
      operating characteristic (ROC) curves to select thresholds that optimized
      sensitivity and specificity in predicting DWI-positive pixels, first using only
      pixels on the side of the brain where infarction was clinically suspected
      ("unilateral" method), then including both sides ("bilateral"). We quantified
      each method and threshold's accuracy in estimating DWI volumes, using sums of
      squared errors (SSE). For the 23 patients with follow-up studies, we assessed
      whether CBF-derived volumes inaccurately exceeded follow-up infarct volumes.
      RESULTS: The areas under the ROC curves were 0.89 (unilateral) and 0.90
      (bilateral). Various metrics selected optimum CBF thresholds ranging from 29%
      32%, with sensitivities of 0.79-0.81, and specificities of 0.83-0.85. However,
      for the unilateral and bilateral methods respectively, volume estimates derived
      from all CBF thresholds above 28% and 22% were less accurate than disregarding
      imaging and presuming every patient's core volume to be zero. The unilateral
      method with a 30% threshold, which recent clinical trials have employed, produced
      a mean core overestimation of 65 mL (range: -82-191), and exceeded follow-up
      volumes for 83% of patients, by up to 191 mL. CONCLUSION: CTP-derived CBF maps
      cannot substitute for DWI in measuring the ischemic core.

PMID- 29190676
TI  - Effects of serum 25-hydroxyvitaminD level on decreased bone mineral density at
      femoral neck and total hip in Chinese type 2 diabetes.
AB  - OBJECTIVE: The aims of this study is to observe the levels of serum 25
      hydroxyvitaminD (25OHD), parathyroid hormone and bone mineral density (BMD) in
      type 2 diabetes as well as to analyze the correlationship between 25OHD level and
      BMD. METHODS: The subjects included 368 type 2 diabetic patients, ages ranged 40
      79 years and 300 non-diabetic control subjects matched for age, gender and body
      mass index. The serum 25OHD concentration, parathyroid hormone level and BMDs
      value at lumbar spine (L1-L4), femoral neck, total hip and total body were
      measured. The BMDs (g/cm2) was measured by LUNAR's DEXA dual-energy X-ray
      absorptiometry. RESULTS: 1Compared with control subjects, the serum 25OHD level,
      BMDs at the femoral neck and total hip declined in type 2 diabetes[(45+/-17 vs.
      36+/-12 nmol/L), (0.93+/-0.17 vs. 0.85+/-0.14 g/cm2), (0.93+/-0.14 vs. 0.87+/
      0.15g/cm2) (all P<0.05)]; The parathyroid hormone level in type 2 diabetes was
      higher in type 2 diabetes than that in control subjects (8.5+/-4.2 vs. 5.6+/-3.9
      pmol/L) (P<0.05). 2Compared with diabetes duration <=10 years group, BMDs at the
      femoral neck and total hip decreased in diabetes duration >10years group [(0.88+/
      0.11 vs. 0.81+/-0.15 g/cm2), (0.91+/-0.14 vs. 0.84+/-0.16 g/cm2)(All P<0.05)];
      The parathyroid hormone level increased in diabetes duration >10years group than
      diabetes duration <=10 years group (10.6+/-9.1 vs. 7.1+/-3.7 pmol/L) (P<0.05). 3
      Compared with hemoglobin A1c (HbA1c) <=8% group, 25OHD and BMDs at the femoral
      neck and total hip in HbA1c>8% group decreased [(40+/-15 vs. 32+/-13 nmol/l),
      (0.89+/-0.13 vs. 0.83+/-0.13 g/cm2), (0.95+/-0.13 vs. 0.83+/-0.16 g/cm2) (All
      P<0.05)] and the parathyroid hormone level increased (7.2+/-4.0 vs. 10.0+/-8.8
      pmol/L) (P<0.05). 4The morbidity of diabetic osteoporosis and osteopenia (41.0%,
      47.8%) were higher than those in control subjects (27.0%,33.3%) (X2 = 4.37 and
      4.70, P = 0.04 and 0.03); Diabetes duration, HbA1c and parathyroid hormone levels
      were longer or higher in Diabetic osteoporosis group than those in normal BMD
      group and osteopenia group(All p<0.05). 5 Simple factor correlation analysis
      showed that the BMD at the femoral neck was negatively correlated with the age,
      diabetes duration, HbA1c, parathyroid hormone (rs = -0.18,-0.23,-0.18,-0.25), and
      positively correlated with 25OHD (rs = 0.23). CONCLUSIONS: Decreased BMDs and
      increased incidence of osteoporosis were observed in type 2 diabetic patients,
      which are closely related to the serum 25OHD level. These findings were more
      prominent at the femoral neck and total hip for patients with a longer diabetic
      history and poor glycemic control.

PMID- 29190677
TI  - Cortical actin nodes: Their dynamics and recruitment of podosomal proteins as
      revealed by super-resolution and single-molecule microscopy.
AB  - Electron tomography of the plasma membrane (PM) identified several layers of
      cortical actin meshwork running parallel to the PM cytoplasmic surface throughout
      the PM. Here, cortical actin structures and dynamics were examined in living
      cells, using super-resolution microscopy, with (x,y)- and z-resolutions of ~140
      and ~400 nm, respectively, and single-molecule imaging. The super-resolution
      microscopy identified sub-micron-sized actin clusters that appeared identical by
      both phalloidin post-fixation staining and Lifeact-mGFP expression followed by
      fixation, and therefore, these actin clusters were named "actin-pl-clusters". In
      live cells, the actin-pl-clusters visualized by Lifeact-mGFP linked two or more
      actin filaments in the fine actin meshwork, acting as a node of the meshwork, and
      dynamically moved on/along the meshwork in a myosin II-dependent manner. Their
      formation depended on the Arp2/3 activities, suggesting that the movements could
      involve both the myosin motor activity and actin polymerization-depolymerization.
      The actin-pl-clusters differ from the actin nodes/asters found previously after
      latrunculin treatments, since myosin II and filamin A were not colocalized with
      the actin-pl-clusters, and the actin-pl-clusters were much smaller than the
      previously reported nodes/asters. The Lifeact linked to a fluorescently-labeled
      transmembrane peptide from syntaxin4 (Lifeact-TM) expressed in the PM exhibited
      temporary immobilization in the PM regions on which actin-pl-clusters and stress
      fibers were projected, showing that >=66% of actin-pl-clusters and 89% of stress
      fibers were located in close proximity (within 3.5 nm) to the PM cytoplasmic
      surface. Podosome-associated cytoplasmic proteins, Tks4, Tks5, cortactin, and N
      WASP, were transiently recruited to actin-pl-clusters, and thus, we propose that
      actin-pl-clusters also represent "actin podosome-like clusters".

PMID- 29190678
TI  - Type I interferon signaling restrains IL-10R+ colonic macrophages and dendritic
      cells and leads to more severe Salmonella colitis.
AB  - Type I interferons (IFNalpha, IFNbeta) are key regulators of innate and adaptive
      immunity, modulating the severity of both viral and bacterial infections. While
      type I IFN signaling leads to improved outcomes in viral infections, its role in
      bacterial infections is more contextual and depends on the specific pathogen and
      route of infection. Given the limited evidence on whether type I IFN signaling
      affects enteric bacterial pathogens, we investigated the role of this signaling
      pathway in Salmonella enterica serovar Typhimurium (S. typhimurium)-induced
      colitis. Comparing mice deficient in IFNAR1- the common receptor for IFNalpha and
      IFNbeta- with wild-type mice, we found that type I IFN signaling leads to more
      rapid death, more severe colonic inflammation, higher serum levels of pro
      inflammatory cytokines, and greater bacterial dissemination. Specific ablation of
      plasmacytoid dendritic cells (pDCs), which are prominent producers of type I IFNs
      in antiviral responses, did not alter survival after infection. This result
      established that pDCs do not play a major role in the pathogenesis of S.
      typhimurium colitis. Flow cytometric analysis of macrophages and conventional
      dendritic cells (cDCs) during active colitis demonstrated an increase in CD11c-
      macrophages and CD103+ cDCs in the colon of Ifnar1-/- animals. Interestingly,
      cells expressing the anti-inflammatory cytokine receptor IL-10R are more abundant
      within these subsets in Ifnar1-/- than in wild-type mice. Moreover, blockade of
      IL-10R in Ifnar1-/- mice increased their susceptibility to S. typhimurium
      colitis, suggesting that altered numbers of these immunoregulatory cells may
      underlie the difference in disease severity. This cross-talk between type I IFN
      and IL-10R signaling pathways may represent a key host cellular mechanism to
      investigate further in order to unravel the balance between pathogenic
      inflammation and homeostasis of the colon. Taken together, our data clearly
      demonstrate that type I IFN signaling is pathogenic in S. typhimurium colitis.

PMID- 29190679
TI  - Infarct morphology assessment in patients with carotid artery/middle cerebral
      artery occlusion using fast fluid-attenuated inversion recovery (FLAIR) vascular
      hyperintensity (FVH).
AB  - We aim to evaluate the value of fast fluid-attenuated inversion recovery (FLAIR)
      vascular hyperintensity (FVH) in assessing infarct morphology in patients with
      symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA)
      occlusions. Magnetic resonance (MR) diffusion-weighted imaging (DWI) FLAIR
      sequences, and carotid/cerebral magnetic resonance angiography of 102 patients
      with symptomatic ICA or MCA occlusions were evaluated. The location and score of
      FVH were determined using Olindo's method; patients were classified as having Low
      or High FVHs based on FVH score, and either Distal or Proximal FVH based on FVH
      location. The differences between infarct morphologies were analyzed. FVH were
      detectable in 62 patients with High FVH and in 40 patients with Low FVHs based on
      the Olindo's scale. There were no statistically significant differences in age,
      gender, hypertension, diabetes, hyperlipidemia, smoking history, and vascular
      occlusive site between High and Low FVHs patients, except for infarct morphology
      (P<0.01). Patients with Distal FVH presented with significant (P<0.01)
      perforating artery and border zone infarcts, whereas those with Proximal FVH had
      significant (P<0.01) large territorial infarcts. The scores and locations of FVH
      could be a predictive imaging marker for infarct morphology in patients with
      symptomatic ICA or MCA occlusion.

PMID- 29190680
TI  - Identifying social factors amongst older individuals in linked electronic health
      records: An assessment in a population based study.
AB  - Identification and quantification of health inequities amongst specific social
      groups is a pre-requisite for designing targeted healthcare interventions. This
      study investigated the recording of social factors in linked electronic health
      records (EHR) of individuals aged >=65 years, to assess the potential of these
      data to identify the social determinants of disease burden and uptake of
      healthcare interventions. Methodology was developed for ascertaining social
      factors recorded on or before a pre-specified index date (01/01/2013) using
      primary care data from Clinical Practice Research Datalink (CPRD) linked to
      hospitalisation and deprivation data in a cross-sectional study. Social factors
      included: religion, ethnicity, immigration status, small area-level deprivation,
      place of residence (including communal establishments such as care homes),
      marital status and living arrangements (e.g. living alone, cohabitation). Each
      social factor was examined for: completeness of recording including improvements
      in completeness by using other linked EHR, timeliness of recording for factors
      that might change over time and their representativeness (compared with English
      2011 Census data when available). Data for 591,037 individuals from 389 practices
      from England were analysed. The completeness of recording varied from 1.6% for
      immigration status to ~80% for ethnicity. Linkages provided the deprivation data
      (available for 82% individuals) and improved completeness of ethnicity recording
      from 55% to 79% (when hospitalisation data were added). Data for ethnicity,
      deprivation, living arrangements and care home residence were comparable to the
      Census data. For time-varying variables such as residence and living alone, ~60%
      and ~35% respectively of those with available data, had this information recorded
      within the last 5 years of the index date. This work provides methods to identify
      social factors in EHR relevant to older individuals and shows that factors such
      as ethnicity, deprivation, not living alone, cohabitation and care home residence
      can be ascertained using these data. Applying these methodologies to routinely
      collected data could improve surveillance programmes and allow assessment of
      health equity in specific healthcare studies.

PMID- 29190681
TI  - Correction: Direct and indirect impact of 10-valent pneumococcal conjugate
      vaccine introduction on pneumonia hospitalizations and economic burden in all age
      groups in Brazil: A time-series analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184204.].

PMID- 29190682
TI  - Cell transmission model of dynamic assignment for urban rail transit networks.
AB  - For urban rail transit network, the space-time flow distribution can play an
      important role in evaluating and optimizing the space-time resource allocation.
      For obtaining the space-time flow distribution without the restriction of
      schedules, a dynamic assignment problem is proposed based on the concept of
      continuous transmission. To solve the dynamic assignment problem, the cell
      transmission model is built for urban rail transit networks. The priority
      principle, queuing process, capacity constraints and congestion effects are
      considered in the cell transmission mechanism. Then an efficient method is
      designed to solve the shortest path for an urban rail network, which decreases
      the computing cost for solving the cell transmission model. The instantaneous
      dynamic user optimal state can be reached with the method of successive average.
      Many evaluation indexes of passenger flow can be generated, to provide effective
      support for the optimization of train schedules and the capacity evaluation for
      urban rail transit network. Finally, the model and its potential application are
      demonstrated via two numerical experiments using a small-scale network and the
      Beijing Metro network.

PMID- 29190683
TI  - Usability study of pH strips for nasogastric tube placement.
AB  - AIMS: (1) To model the process of use and usability of pH strips (2) to identify,
      through simulation studies, the likelihood of misreading pH strips, and to assess
      professional's acceptance, trust and perceived usability of pH strips. METHODS:
      This study was undertaken in four phases and used a mixed method approach (an
      audit, a semi-structured interview, a survey and simulation study). The three
      months audit was of 24 patients, the semi-structured interview was performed with
      19 health professionals and informed the process of use of pH strips. A survey of
      134 professionals and novices explored the likelihood of misinterpreting pH
      strips. Standardised questionnaires were used to assess professionals perceived
      usability, trust and acceptance of pH strip use in a simulated study. RESULTS:
      The audit found that in 45.7% of the cases aspiration could not be achieved, and
      that 54% of the NG-tube insertions required x-ray confirmation. None of those
      interviewed had received formal training on pH strips use. In the simulated
      study, participants made up to 11.15% errors in reading the strips with important
      implications for decision making regarding NG tube placement. No difference was
      identified between professionals and novices in their likelihood of
      misinterpreting the pH value of the strips. Whilst the overall experience of
      usage is poor (47.3%), health professionals gave a positive level of trust in
      both the interview (62.6%) and the survey (68.7%) and acceptance (interview group
      65.1%, survey group 74.7%). They also reported anxiety in the use of strips
      (interview group 29.7%, survey group 49.7%). CONCLUSIONS: Significant errors
      occur when using pH strips in a simulated study. Manufacturers should consider
      developing new pH strips, specifically designed for bedside use, that are more
      usable and less likely to be misread.

PMID- 29190684
TI  - Respiratory syncytial and influenza viruses in children under 2 years old with
      severe acute respiratory infection (SARI) in Maputo, 2015.
AB  - INTRODUCTION: Although respiratory syncytial virus (RSV) and influenza virus
      (influenza) infections are one of the leading causes of Severe Acute Respiratory
      Infections (SARI) and death in young children worldwide, little is known about
      the burden of these pathogens in Mozambique. MATERIAL AND METHODS: From January
      2015 to January 2016, nasopharyngeal swabs from 450 children, aged <=2 years, who
      had been admitted to the Pediatric Department of the Maputo Central Hospital
      (HCM) in Mozambique, suffering with SARI were enrolled and tested for influenza
      and RSV using a real-time PCR assay. RESULTS: Influenza and RSV were detected in
      2.4% (11/450) and 26.7% (113/424) of the participants. Children with influenza
      were slightly older than those infected with RSV (10 months in influenza-infected
      children compared to 3 months in RSV-infected children); male children were
      predominant in both groups (63.6% versus 54.9% in children with influenza and
      RSV, respectively). There was a trend towards a higher frequency of influenza
      (72.7%) and RSV (93.8%) cases in the dry season. Bronchopneumonia, bronchitis and
      respiratory distress were the most common diagnoses at admission. Antibiotics
      were administered to 27,3% and 15,9% of the children with influenza and RSV,
      respectively. Two children, of whom, one was positive for RSV (aged 6 months) and
      another was positive for Influenza (aged 3 months) died; both were children of
      HIV seropositive mothers and had bronchopneumonia. CONCLUSIONS: Our data
      demonstrated that RSV, and less frequently influenza, occurs in children with
      SARI in urban/sub-urban settings from southern Mozambique. The occurrence of
      deaths in small children suspected of being HIV-infected, suggests that
      particular attention should be given to this vulnerable population. Our data also
      provide evidence of antibiotics prescription in children with respiratory viral
      infection, which represents an important public health problem and calls for
      urgent interventions.

PMID- 29190685
TI  - Evaluation of RNAi and CRISPR technologies by large-scale gene expression
      profiling in the Connectivity Map.
AB  - The application of RNA interference (RNAi) to mammalian cells has provided the
      means to perform phenotypic screens to determine the functions of genes. Although
      RNAi has revolutionized loss-of-function genetic experiments, it has been
      difficult to systematically assess the prevalence and consequences of off-target
      effects. The Connectivity Map (CMAP) represents an unprecedented resource to
      study the gene expression consequences of expressing short hairpin RNAs (shRNAs).
      Analysis of signatures for over 13,000 shRNAs applied in 9 cell lines revealed
      that microRNA (miRNA)-like off-target effects of RNAi are far stronger and more
      pervasive than generally appreciated. We show that mitigating off-target effects
      is feasible in these datasets via computational methodologies to produce a
      consensus gene signature (CGS). In addition, we compared RNAi technology to
      clustered regularly interspaced short palindromic repeat (CRISPR)-based knockout
      by analysis of 373 single guide RNAs (sgRNAs) in 6 cells lines and show that the
      on-target efficacies are comparable, but CRISPR technology is far less
      susceptible to systematic off-target effects. These results will help guide the
      proper use and analysis of loss-of-function reagents for the determination of
      gene function.

PMID- 29190686
TI  - Assessment of accuracy, fix success rate, and use of estimated horizontal
      position error (EHPE) to filter inaccurate data collected by a common
      commercially available GPS logger.
AB  - Global positioning system (GPS) technologies have improved the ability of
      researchers to monitor wildlife; however, use of these technologies is often
      limited by monetary costs. Some researchers have begun to use commercially
      available GPS loggers as a less expensive means of tracking wildlife, but data
      regarding performance of these devices are limited. We tested a commercially
      available GPS logger (i-gotU GT-120) by placing loggers at ground control points
      with locations known to < 30 cm. In a preliminary investigation, we collected
      locations every 15 minutes for several days to estimate location error (LE) and
      circular error probable (CEP). Using similar methods, we then investigated the
      influence of cover on LE, CEP, and fix success rate (FSR) by constructing cover
      over ground control points. We found mean LE was < 10 m and mean 50% CEP was < 7
      m. FSR was not significantly influenced by cover and in all treatments remained
      near 100%. Cover had a minor but significant effect on LE. Denser cover was
      associated with higher mean LE, but the difference in LE between the no cover and
      highest cover treatments was only 2.2 m. Finally, the most commonly used
      commercially available devices provide a measure of estimated horizontal position
      error (EHPE) which potentially may be used to filter inaccurate locations. Using
      data combined from the preliminary and cover investigations, we modeled LE as a
      function of EHPE and number of satellites. We found support for use of both EHPE
      and number of satellites in predicting LE; however, use of EHPE to filter
      inaccurate locations resulted in the loss of many locations with low error in
      return for only modest improvements in LE. Even without filtering, the accuracy
      of the logger was likely sufficient for studies which can accept average location
      errors of approximately 10 m.

PMID- 29190687
TI  - Leptin reverses hyperglycemia and hyperphagia in insulin deficient diabetic rats
      by pituitary-independent central nervous system actions.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis has been postulated to play a major
      role in mediating the antidiabetic effects of leptin. We tested if the pituitary
      is essential for the chronic central nervous system mediated actions of leptin on
      metabolic and cardiovascular function in insulin-dependent diabetic and non
      diabetic rats. Male 12-week-old hypophysectomized Sprague-Dawley rats (Hypo, n =
      5) were instrumented with telemetry probes for determination of mean arterial
      pressure (MAP) and heart rate (HR) 24-hrs/day and an intracerebroventricular
      (ICV) cannula was placed into the brain lateral ventricle for continuous leptin
      infusion. In additional groups of Hypo and control rats (n = 5/group), diabetes
      was induced by single injection of streptozotocin (50 mg/kg, IP). Hypo rats were
      lighter, had lower MAP and HR (83+/-4 and 317+/-2 vs 105+/-4 mmHg and 339+/-4
      bpm), with similar caloric intake per kilogram of body weight and fasting plasma
      glucose levels (84+/-4 vs 80+/-4 mg/dl) compared to controls. Chronic ICV leptin
      infusion (7 days, 0.62 MUg/hr) in non-diabetic rats reduced caloric intake and
      body weight (-10%) in Hypo and control rats and markedly increased HR in control
      rats (~25 bpm) while causing only modest HR increases in Hypo rats (8 bpm). In
      diabetic Hypo and control rats, leptin infusion reduced caloric intake, body
      weight and glucose levels (323+/-74 to 99+/-20 and 374+/-27 to 108+/-10 mg/dl),
      respectively; however, the effects of leptin on HR were abolished in Hypo rats.
      These results indicate that hypophysectomy attenuates leptin's effect on HR
      regulation without altering leptin's ability to suppress appetite or normalize
      glucose levels in diabetes.

PMID- 29190688
TI  - Spatial and temporal profile of cisplatin delivery by ultrasound-assisted
      intravesical chemotherapy in a bladder cancer model.
AB  - Non-muscle invasive bladder cancer is one of the most common tumors of the
      urinary tract. Despite the current multimodal therapy, recurrence and progression
      of disease have been challenging problems. We hereby introduced a new approach,
      ultrasound-assisted intravesical chemotherapy, intravesical instillation of
      chemotherapeutic agents and microbubbles followed by ultrasound exposure. We
      investigated the feasibility of the treatment for non-muscle invasive bladder
      cancer. In order to evaluate intracellular delivery and cytotoxic effect as a
      function to the thickness, we performed all experiments using a bladder cancer
      mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased
      both the intracellular platinum concentration and the cytotoxic effect of
      cisplatin at the thickness of 70 and 122 MUm of the culture model. The duration
      of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble
      cavitation was approximately 1 hr. Based on the distance and duration of
      delivery, we further tested the feasibility of repetition of the treatment.
      Triple treatment increased the effective distance by 1.6-fold. Our results
      clearly showed spatial and temporal profile of delivery by ultrasound-triggered
      microbubble cavitation in a tumor-mimicking structure. Furthermore, we
      demonstrated that the increase in intracellular concentration results in the
      enhancement of the cytotoxic effect in a structure with the certain thickness.
      Repetition of ultrasound exposure would be treatment of choice in future clinical
      application. Our results suggest ultrasound-triggered microbubble cavitation can
      be repeatable and is promising for the local control of non-muscle invasive
      bladder cancer.

PMID- 29190689
TI  - Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins
      from Manilkara rufula.
AB  - The infection caused by Trichomonas vaginalis is the most common but overlooked
      non-viral sexually transmitted disease worldwide. Treatment relies on one class
      of drugs, the 5-nitroimidazoles, but resistance is widespread. New drugs are
      urgently needed. We reported the effect of crude and purified saponin fractions
      of Manilkara rufula against Trichomonas vaginalis. The compound responsible for
      antitrichomonal activity was isolated and identified as an uncommon bidesmosic
      saponin, Mi-saponin C. This saponin eliminated parasite viability without
      toxicity against the human vaginal epithelial line (HMVII). In addition, the
      isolated saponin fraction improved the metronidazole effect against a
      metronidazole-resistant isolate and dramatically reduced the cytoadherence of T.
      vaginalis to human cells. Investigation of the mechanism of death showed that the
      saponin fraction induced the parasite death due to profound membrane damage,
      inducing a disturbance of intracellular content without nuclear damage. To the
      best of our knowledge, this is the first report of antitrichomonal activity in
      the bidesmosic saponins of Manilkara rufula.

PMID- 29190691
TI  - Premedical special master's programs increase USMLE STEP1 scores and improve
      residency placements.
AB  - The effectiveness of Special Master's Programs (SMPs) in benefiting a potential
      medical student's career beyond admission into an MD-program is largely unknown.
      This study aims to evaluate the role of SMPs, if any, in affecting the
      performance and outcomes of students during their medical school career. This
      study analyzed anonymous surveys of students and residents from the University of
      Toledo. The data analysis is used to evaluate a student's academic performance
      before, during and after medical school. Measured metrics included: MCAT Scores,
      undergraduate GPA, USMLE STEP 1 scores, participation in research, number of
      research publications, and residency placement. Of 500 people surveyed 164
      medical students or residents responded. Based on their responses, the
      respondents were divided into traditional (non-SMP) and SMP groups. As
      anticipated, MCAT scores (SMP: 29.82 vs. traditional 31.10) are significantly
      (p<0.05) different between the two groups. Interestingly, there is no significant
      difference in USMLE STEP 1 scores (SMP: 232.7 vs. traditional: 233.8) and when
      normalized relative to MCAT scores, USMLE STEP 1 scores for SMP-students are
      significantly (p<0.05) higher than their traditional counterparts (p<0.05).
      Additionally, SMP-students did not outperform the traditional students with
      regards to research publications. But, they did demonstrate a significant
      (p<0.05) proclivity towards surgical residencies when compared to the traditional
      students. Overall, our results highlight that SMPs potentiate USMLE STEP 1
      performance and competitive residency-placements for its students.

PMID- 29190690
TI  - Development of effective tumor immunotherapy using a novel dendritic cell
      targeting Toll-like receptor ligand.
AB  - Although dendritic cell (DC)-based immunotherapy shows little toxicity,
      improvements should be necessary to obtain satisfactory clinical outcome. Using
      interferon-gamma injection along with DCs, we previously obtained significant
      clinical responses against small or early stage malignant tumors in dogs.
      However, improvement was necessary to be effective to largely developed or
      metastatic tumors. To obtain effective methods applicable to those tumors, we
      herein used a DC-targeting Toll-like receptor ligand, h11c, and examined the
      therapeutic effects in murine subcutaneous and visceral tumor models and also in
      the clinical treatment of canine cancers. In murine experiments, most and
      significant inhibition of tumor growth and extended survival was observed in the
      group treated with the combination of h11c-activated DCs in combination with
      interferon-gamma and a cyclooxygenase2 inhibitor. Both monocytic and granulocytic
      myeloid-derived suppressor cells were significantly reduced by the combined
      treatment. Following the successful results in mice, the combined treatment was
      examined against canine cancers, which spontaneously generated like as those in
      human. The combined treatment elicited significant clinical responses against a
      nonepithelial malignant tumor and a malignant fibrous histiocytoma. The treatment
      was also successful against a bone-metastasis of squamous cell carcinoma. In the
      successful cases, the marked increase of tumor-responding T cells and decrease of
      myeloid-derived suppressor cells and regulatory T cells was observed in their
      peripheral blood. Although the combined treatment permitted the growth of lung
      cancer of renal carcinoma-metastasis, the marked elevated and long-term
      maintaining of the tumor-responding T cells was observed in the patient dog.
      Overall, the combined treatment gave rise to emphatic amelioration in DC-based
      cancer therapy.

PMID- 29190692
TI  - Transcatheter arterial chemoembolization after stopping sorafenib therapy for
      advanced hepatocellular carcinoma.
AB  - Targeted therapy is currently the standard treatment for advanced hepatocellular
      carcinoma (HCC), but an effective treatment after the discontinuation of
      sorafenib therapy remains uncertain. We aim to investigate the survival benefits
      of transcatheter arterial chemoembolization (TACE) after stopping sorafenib
      therapy. We retrospectively analyzed all patients with advanced HCC, who had
      received palliative TACE after terminating sorafenib therapy, from January 2008
      to June 2016. Patients who were in the terminal stage (Child-Pugh class C or
      performance status 3-4), who received a liver transplantation, or who had
      received any HCC treatment other than TACE, were excluded. Finally, 28 patients
      were recruited as the TACE group, and were randomly matched 1:1 by age, gender,
      Child-Pugh class, extrahepatic metastasis, and portal vein thrombosis with 28
      controls who only received supportive care. For avoiding any immortal time bias,
      the index date of outcome follow-up was also matched. Cumulative incidences of,
      and hazard ratios (HRs) for, patient mortality were analyzed. The baseline
      demographic data between the TACE group and the control group were similar, but
      the 1-year overall survival rate in the TACE group was significantly higher than
      that of the control group (41.2%, 95% confidence interval [CI]: 19.4-63.0% vs.
      24.5%, 95% CI: 6.3-42.7%; p < 0.01). In multivariate analysis, after adjusting
      for alpha-fetoprotein > 400ng/mL, Child-Pugh class B, and tumor extension > 50%
      of liver volume, TACE was independently associated with a decreased mortality
      risk(HR 0.19, 95% CI: 0.08-0.42). In addition, tumor extension > 50% of the liver
      was another independent prognostic factor associated with an increased mortality
      risk (HR 2.99, 95% CI: 1.31-6.82). Multivariate stratified analyses verified the
      association of TACE with a decreased mortality rate in each patient subgroup (all
      HR < 1.0). By controlling intrahepatic tumor growth, TACE may be a treatment
      option for use in improving patient survival in advanced HCC, after the
      termination of sorafenib therapy.

PMID- 29190693
TI  - Criterion validity of 8-item Morisky Medication Adherence Scale in patients with
      asthma.
AB  - The 8-item Morisky Medication Adherence Scale (MMAS-8) is reliable and valid in
      patients with hypertension, but to our knowledge validity has not been
      established for patients with asthma. The aim of the study was to determine the
      criterion validity of the MMAS-8 in patients with asthma. In the cross-sectional
      study patients older than 12 year were recruited when dispensed asthma
      medications in community pharmacies. Criterion validity of the scale was assessed
      through associations with asthma control and quality of life. Asthma control was
      assessed by the Asthma Control Test (ACT) and quality of life was evaluated by
      the Saint George Respiratory Questionnaire (SGRQ). A total of 208 patients (mean
      age 56 years, 59% female) were included in the study. Almost all patients were
      prescribed inhaled corticosteroids (96%). Asthma was not controlled in 37% of the
      patients and 22% experienced at least one exacerbation requiring emergency room
      visit, hospitalization or treatment with oral corticosteroid therapy in the
      previous year. The 8-item MMAS was significantly associated with asthma control
      and quality of life. Patients who scored 8 points, <8 to >6 points and <=6 points
      on the scale were considered to have high, medium and low adherence,
      respectively. High, medium and low adherence was found in 53%, 23% and 24% of the
      patients, respectively. As adherence improved from low to medium or from medium
      to high, the odds of asthma control increased by 1.7 times (OR 1.65, p = 0.027).
      Patients with high and medium adherence had SGRQ scores that were 6.1 and 5.3
      points lower, respectively, compared with patients with low adherence. The MMAS-8
      was found to be valid for assessing medication adherence and predicting health
      outcomes in patients with asthma.

PMID- 29190694
TI  - Contrast-enhanced magnetic resonance imaging for the detection of ruptured
      coronary plaques in patients with acute myocardial infarction.
AB  - PURPOSE: X-ray coronary angiography (XCA) is the current gold standard for the
      assessment of lumen encroaching coronary stenosis but XCA does not allow for
      early detection of rupture-prone vulnerable plaques, which are thought to be the
      precursor lesions of most acute myocardial infarctions (AMI) and sudden death.
      The aim of this study was to investigate the potential of delayed contrast
      enhanced magnetic resonance coronary vessel wall imaging (CE-MRCVI) for the
      detection of culprit lesions in the coronary arteries. METHODS: 16 patients (13
      male, age 61.9+/-8.6 years) presenting with sub-acute MI underwent CE-MRCVI
      within 24-72h prior to invasive XCA. CE-MRCVI was performed using a T1-weighted
      3D gradient echo inversion recovery sequence (3D IR TFE) 40+/-4 minutes following
      the administration of 0.2 mmol/kg gadolinium-diethylenetriamine-pentaacetic acid
      (DTPA) on a 3T MRI scanner equipped with a 32-channel cardiac coil. RESULTS: 14
      patients were found to have culprit lesions (7x LAD, 1xLCX, 6xRCA) as identified
      by XCA. Quantitative CE-MRCVI correctly identified the culprit lesion location
      with a sensitivity of 79% and excluded culprit lesion formation with a
      specificity of 99%. The contrast to noise ratio (CNR) of culprit lesions (9.7+/
      4.1) significantly exceeded CNR values of segments without culprit lesions (2.9+/
      1.9, p<0.001). CONCLUSION: CE-MRCVI allows the selective visualization of culprit
      lesions in patients immediately after myocardial infarction (MI). The pronounced
      contrast uptake in ruptured plaques may represent a surrogate biomarker of plaque
      activity and/or vulnerability.

PMID- 29190695
TI  - High-accuracy detection of early Parkinson's Disease using multiple
      characteristics of finger movement while typing.
AB  - Parkinson's Disease (PD) is a progressive neurodegenerative movement disease
      affecting over 6 million people worldwide. Loss of dopamine-producing neurons
      results in a range of both motor and non-motor symptoms, however there is
      currently no definitive test for PD by non-specialist clinicians, especially in
      the early disease stages where the symptoms may be subtle and poorly
      characterised. This results in a high misdiagnosis rate (up to 25% by non
      specialists) and people can have the disease for many years before diagnosis.
      There is a need for a more accurate, objective means of early detection, ideally
      one which can be used by individuals in their home setting. In this
      investigation, keystroke timing information from 103 subjects (comprising 32 with
      mild PD severity and the remainder non-PD controls) was captured as they typed on
      a computer keyboard over an extended period and showed that PD affects various
      characteristics of hand and finger movement and that these can be detected. A
      novel methodology was used to classify the subjects' disease status, by utilising
      a combination of many keystroke features which were analysed by an ensemble of
      machine learning classification models. When applied to two separate participant
      groups, this approach was able to successfully discriminate between early-PD
      subjects and controls with 96% sensitivity, 97% specificity and an AUC of 0.98.
      The technique does not require any specialised equipment or medical supervision,
      and does not rely on the experience and skill of the practitioner. Regarding more
      general application, it currently does not incorporate a second cardinal disease
      symptom, so may not differentiate PD from similar movement-related disorders.

PMID- 29190696
TI  - Asymmetry of price returns-Analysis and perspectives from a non-extensive
      statistical physics point of view.
AB  - We study how the approach grounded on non-extensive statistical physics can be
      applied to describe and distinguish different stages of the stock and money
      market development. A particular attention is given to asymmetric behavior of fat
      tailed distributions of positive and negative returns. A new method to measure
      this asymmetry is proposed. It is based on the value of the non-extensive Tsallis
      parameter q. The new quantifier of the relative asymmetry level between tails in
      terms of the Tsallis parameters q+/- is provided to analyze the effect of memory
      in data caused by nonlinear autocorrelations. The presented analysis takes into
      account data of separate stocks from the main developing stock market in Europe,
      i.e., the Warsaw Stock Exchange (WSE) in Poland and-for comparison-data from the
      most mature money market (Forex). It is argued that the proposed new quantifier
      is able to describe the stage of market development and its robustness to
      speculation. The main strength is put on a description and interpretation of the
      asymmetry between statistical properties of positive and negative returns for
      various stocks and for diversified time-lags Deltat of data counting. The
      particular caution in this context is addressed to the difference between
      intraday and interday returns. Our search is extended to study memory effects and
      their dependence on the quotation frequency for similar large companies-owners of
      food-industrial retail supermarkets acting on both Polish and European markets
      (Eurocash, Jeronimo-Martins, Carrefour, Tesco)-but traded on various European
      stock markets of diversified economical maturity (respectively in Warsaw, Lisbon,
      Paris and London). The latter analysis seems to indicate quantitatively that
      stocks from the same economic sector traded on different markets within European
      Union (EU) may be a target of diversified level of speculations involved in
      trading independently on the true economic situation of the company. Our work
      thus gives indications that the statement:" where you are is more important than
      who you are" is true on trading markets.

PMID- 29190697
TI  - Formal comment on: Piscine reovirus: Genomic and molecular phylogenetic analysis
      from farmed and wild salmonids collected on the Canada/US Pacific Coast.

PMID- 29190698
TI  - Profiles of a broad spectrum of epigenetic DNA modifications in normal and
      malignant human cell lines: Proliferation rate is not the major factor
      responsible for the 5-hydroxymethyl-2'-deoxycytidine level in cultured cancerous
      cell lines.
AB  - Active demethylation of 5-methylcytosine moiety in DNA occurs by its sequential
      oxidation to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine,
      catalysed by enzymes of the Ten-Eleven Translocation family proteins (TETs 1, 2
      and 3). Here we analyzed for the first time all the intermediate products of DNA
      demethylation pathway in the form of deoxynucleosides (5-methyl-2'-deoxycytidine,
      5-(hydroxymethyl)-2'-deoxycytidine, 5-formyl-2'-deoxycytidine and 5-carboxy-2'
      deoxycytidine as well as 5-(hydroxymethyl)-2'-deoxyuridine) using automated
      isotope-dilution online two-dimensional ultra-performance liquid chromatography
      with tandem mass spectrometry. DNA was isolated from human malignant cell lines
      of colon adenocarcinoma (HCT 116), melanoma (Me45), myelogenous leukemia bone
      marrow blasts (K562), EBV-positive Burkitt's lymphoma lymphoblasts (Raji), EBV
      negative Burkitt's lymphoma lymphoblasts (male-CA46 and female-ST486), as well as
      normal neonatal dermal fibroblasts (NHDF-Neo). The expression levels of TET1,
      TET2, TET3, SMUG1, and TDG genes were also assayed by RT-qPCR. Our results show a
      global erasure of 5-hydroxymethyl-2'-deoxycytidine and 5-carboxy-2'-deoxycytidine
      in DNA of cultured cells compared with DNA from primary malignant tissue.
      Moreover, malignant cells in culture have a quite different DNA epigenetic
      profile than cultured normal cells, and different types of malignant cells
      display different and characteristic profiles of DNA epigenetic marks. Similar
      analyses of a broader spectrum of epigenetic modifications, not restricted to 5
      methyl-2'-deoxycytidine, could lead to better understanding of the mechanism(s)
      responsible for emergence of different types of cancer cells.

PMID- 29190699
TI  - Cost-effectiveness of expanding childhood routine immunization against Neisseria
      meningitidis serogroups C, W and Y with a quadrivalent conjugate vaccine in the
      African meningitis belt.
AB  - BACKGROUND: Neisseria meningitidis constitutes a major public health problem
      among countries in the African meningitis belt. Following regional vaccination
      campaigns for serogroup A and subsequent increases in protection against this
      serogroup, non-A serogroups such as C and W now pose significant epidemic
      threats, particularly in young children. OBJECTIVE: To evaluate the cost
      effectiveness of broadening coverage from conjugate serogroup A to quadrivalent
      ACWY vaccination. METHODS: We developed a 40-year Markov state transition model
      with annual cycles to simulate costs and clinical outcomes in children aged 1 to
      10 in the 26 countries of the African meningitis belt. The incidence of CWY
      meningitis cases among an unvaccinated population was held constant at inter
      epidemic rates of 50 per 100,000/year and 150 per 100,000/year. The country
      specific cost and probability of access to meningitis care, vaccine efficacy, the
      mortality risk among treated and untreated meningitis cases, the risk of clinical
      sequelae and their respective disability weights were based on published sources.
      Vaccination cost was based on international prices lists, presented in 2014 US$.
      RESULTS: At an incidence rate of 50 per 100,000/year, routine conjugate
      vaccination is highly cost-effective in 14 out of 26 countries with a cost/DALY
      averted ranging from US$555-US$787. At the higher incidence rate of 150 per
      100,000/year, quadrivalent vaccination is cost-effective in all 26 countries with
      a cost/DALY averted ranging from US$105-US$250. The annual incidence rate at
      which routine conjugate quadrivalent vaccination is expected to be economically
      justifiable ranges from 13 per 100,000/year in Nigeria to 142 per 100,000/year in
      Burundi. CONCLUSION: Routine quadrivalent conjugate vaccination against Neisseria
      meningitidis is cost-effective at incidence rates well below the epidemic
      threshold among children living in the African meningitis belt.

PMID- 29190700
TI  - Evaluation of the difference in caries experience in diabetic and non-diabetic
      children-A case control study.
AB  - AIM: To evaluate the caries prevalence and related variables in Type 1 diabetic
      and non-diabetic children and among the diabetic children according to their
      metabolic status. METHODS: Sixty-eight diabetic and 136 non-diabetic children,
      matching by gender and age (4-14 years) were enrolled. The diabetic children were
      divided: a) 20 children in good metabolic control (Hb1ac<=7.5) and b) 48 children
      in bad metabolic control (Hb1ac>7.5). Dietary and oral hygiene habits were
      investigated. Caries status was registered using the International Caries
      Detection and Assessment System. Oral microflora was analysed using the
      checkerboard DNA-DNA hybridisation method. Plaque acidogenicity was recorded
      after a sucrose rinse. RESULTS: Sugared beverage and snack intake was higher in
      diabetic group compared to non-diabetic group (p = 0.03 and p = 0.04,
      respectively) and in subjects in bad metabolic control (p = 0.03 and p<0.01,
      respectively). Oral hygiene habits were similar, except for the use of
      fluoridated adjuvants, higher in non-diabetic children (p = 0.04). No
      statistically significant differences were observed regarding caries figures, but
      a higher number of caries free subjects was found in diabetic subjects in good
      metabolic control (p<0.01). Significant difference for the main cariogenic
      bacteria was found between diabetic and non-diabetic subjects (p<0.05). The pH
      values showed statistically significant differences between diabetic and non
      diabetic subjects and between diabetic subjects in good and bad metabolic control
      (p<0.01). CONCLUSIONS: Diabetic children in good metabolic control might even be
      considered at low caries risk, while those in bad metabolic control showed an
      oral environment prone to a high caries risk.

PMID- 29190702
TI  - The infection and impact of Azorhizobium caulinodans ORS571 on wheat (Triticum
      aestivum L.).
AB  - Based on our previous study, cereal crop wheat (Triticum aestivum L.) could be
      infected by rhizobia Azorhizobium caulinodans ORS571, and form para-nodules with
      the induction of 2.4-dichlorophenoxyacetic acid, a common plant growth regulator.
      To enhance this infection and the potential agricultural application, we compared
      six different infection methods (Direct seed dip; Seed germination dip; Pruned
      root dip; Foliar spray; Circum-soil dip; Seed dip and circum-soil dip) for
      achieving the high efficient infection of A. caulinodans into wheat plants by
      employing a green fluorescent protein (gfp)-labeled Azorhizobium caulinodans
      strain ORS571. With proper methods, copious rhizobia could enter the interior and
      promote the growth of wheat to the hilt. Circum-soil dip was proved to be the
      most efficient method, seed germination dip and pruned-root dip is the last
      recommended to infect wheat, seed germination dip and seed dip and circum-soil
      dip showed better effects on plant growth, pruned-root dip did not show too much
      effect on plant growth. This study laid the foundation for understanding the
      interaction between rhizobia and cereal crops and the growth-promoting function
      of rhizobia.

PMID- 29190701
TI  - A non-threshold region-specific method for detecting rare variants in complex
      diseases.
AB  - A region-specific method, NTR (non-threshold rare) variant detection method, was
      developed-it does not use the threshold for defining rare variants and accounts
      for directions of effects. NTR also considers linkage disequilibrium within the
      region and accommodates common and rare variants simultaneously. NTR weighs
      variants according to minor allele frequency and odds ratio to combine the
      effects of common and rare variants on disease occurrence into a single score and
      provides a test statistic to assess the significance of the score. In the
      simulations, under different effect sizes, the power of NTR increased as the
      effect size increased, and the type I error of our method was controlled well.
      Moreover, NTR was compared with several other existing methods, including the
      combined multivariate and collapsing method (CMC), weighted sum statistic method
      (WSS), sequence kernel association test (SKAT), and its modification, SKAT-O. NTR
      yields comparable or better power in simulations, especially when the effects of
      linkage disequilibrium between variants were at least moderate. In an analysis of
      diabetic nephropathy data, NTR detected more confirmed disease-related genes than
      the other aforementioned methods. NTR can thus be used as a complementary tool to
      help in dissecting the etiology of complex diseases.

PMID- 29190703
TI  - Developing an eye-tracking algorithm as a potential tool for early diagnosis of
      autism spectrum disorder in children.
AB  - BACKGROUND: Autism spectrum disorder (ASD) currently affects nearly 1 in 160
      children worldwide. In over two-thirds of evaluations, no validated diagnostics
      are used and gold standard diagnostic tools are used in less than 5% of
      evaluations. Currently, the diagnosis of ASD requires lengthy and expensive
      tests, in addition to clinical confirmation. Therefore, fast, cheap, portable,
      and easy-to-administer screening instruments for ASD are required. Several
      studies have shown that children with ASD have a lower preference for social
      scenes compared with children without ASD. Based on this, eye-tracking and
      measurement of gaze preference for social scenes has been used as a screening
      tool for ASD. Currently available eye-tracking software requires intensive
      calibration, training, or holding of the head to prevent interference with gaze
      recognition limiting its use in children with ASD. METHODS: In this study, we
      designed a simple eye-tracking algorithm that does not require calibration or
      head holding, as a platform for future validation of a cost-effective ASD
      potential screening instrument. This system operates on a portable and
      inexpensive tablet to measure gaze preference of children for social compared to
      abstract scenes. A child watches a one-minute stimulus video composed of a social
      scene projected on the left side and an abstract scene projected on the right
      side of the tablet's screen. We designed five stimulus videos by changing the
      social/abstract scenes. Every child observed all the five videos in random order.
      We developed an eye-tracking algorithm that calculates the child's gaze
      preference for the social and abstract scenes, estimated as the percentage of the
      accumulated time that the child observes the left or right side of the screen,
      respectively. Twenty-three children without a prior history of ASD and 8 children
      with a clinical diagnosis of ASD were evaluated. The recorded video of the
      child's eye movement was analyzed both manually by an observer and automatically
      by our algorithm. RESULTS: This study demonstrates that the algorithm correctly
      differentiates visual preference for either the left or right side of the screen
      (social or abstract scenes), identifies distractions, and maintains high accuracy
      compared to the manual classification. The error of the algorithm was 1.52%, when
      compared to the gold standard of manual observation. DISCUSSION: This tablet
      based gaze preference/eye-tracking algorithm can estimate gaze preference in both
      children with ASD and without ASD to a high degree of accuracy, without the need
      for calibration, training, or restraint of the children. This system can be
      utilized in low-resource settings as a portable and cost-effective potential
      screening tool for ASD.

PMID- 29190704
TI  - Electrocortical correlates of human level-ground, slope, and stair walking.
AB  - This study investigated electrocortical dynamics of human walking across
      different unconstrained walking conditions (i.e., level ground (LW), ramp ascent
      (RA), and stair ascent (SA)). Non-invasive active-electrode scalp
      electroencephalography (EEG) signals were recorded and a systematic EEG
      processing method was implemented to reduce artifacts. Source localization
      combined with independent component analysis and k-means clustering revealed the
      involvement of four clusters in the brain during the walking tasks: Left and
      Right Occipital Lobe (LOL, ROL), Posterior Parietal Cortex (PPC), and Central
      Sensorimotor Cortex (SMC). Results showed that the changes of spectral power in
      the PPC and SMC clusters were associated with the level of motor task demands.
      Specifically, we observed alpha and beta suppression at the beginning of the gait
      cycle in both SA and RA walking (relative to LW) in the SMC. Additionally, we
      observed significant beta rebound (synchronization) at the initial swing phase of
      the gait cycle, which may be indicative of active cortical signaling involved in
      maintaining the current locomotor state. An increase of low gamma band power in
      this cluster was also found in SA walking. In the PPC, the low gamma band power
      increased with the level of task demands (from LW to RA and SA). Additionally,
      our results provide evidence that electrocortical amplitude modulations (relative
      to average gait cycle) are correlated with the level of difficulty in locomotion
      tasks. Specifically, the modulations in the PPC shifted to higher frequency bands
      when the subjects walked in RA and SA conditions. Moreover, low gamma modulations
      in the central sensorimotor area were observed in the LW walking and shifted to
      lower frequency bands in RA and SA walking. These findings extend our
      understanding of cortical dynamics of human walking at different level of
      locomotion task demands and reinforces the growing body of literature supporting
      a shared-control paradigm between spinal and cortical networks during locomotion.

PMID- 29190706
TI  - Elderly emergency patients presenting with non-specific complaints:
      Characteristics and outcomes.
AB  - BACKGROUND: Non-specific complaints (NSC) are common at the emergency department,
      but only a few studies have shown evidence that these complaints are associated
      with a poor prognosis in elderly emergency patients. OBJECTIVE: To describe
      patient characteristics and outcomes in a cohort of elderly emergency patients
      presenting with NSC. Outcomes were: patient characteristics, hospitalization, 90
      day ED-return visits, and 30-day mortality. METHOD: A retrospective cohort study
      was conducted amongst elderly patients present to the Internal Medicine Emergency
      Department (ED) between 01-09-2010 and 31-08-2011. NSC were defined as
      indefinable complaints that lack a pre-differential diagnosis needed to initiate
      of a standardized patient evaluation. Cox regression was performed to calculate
      Hazard Ratios (HR) and corrected for confounders such as comorbidity. RESULTS: In
      total, 1784 patients were enrolled; 244 (13.7%) presented with NSC. Compared to
      those with SC, comorbidity was higher in the NSC-group (Charlson comorbidity
      index 3.0 vs. 2.4, p<0.001). The triage level did not differ, but ED-length of
      stay was longer in the NSC-group (188 vs. 178 minutes, p = 0.004).
      Hospitalization was more frequent (84.0 vs. 71.1%, p<0.001) and the length of
      hospital stay (9 vs. 6 days, p<0.001 was longer in the NSC- than in the SC-group.
      The number of ED-return visits were comparable between both groups (HR 0.8, 95%CI
      0.6-1.1). Mortality within 30-days was higher in the NSC- (20.1%) than in the SC
      group (11.0%, HR 1.7 95%CI 1.2-2.4). CONCLUSION: Elderly patients present with
      NSC at the ED regularly. These patients are more often hospitalized and have a
      substantially higher 30-day mortality than patients with SC.

PMID- 29190705
TI  - Arthritic role of Porphyromonas gingivalis in collagen-induced arthritis mice.
AB  - Epidemiological studies show an association between rheumatoid arthritis (RA) and
      periodontal disease. Porphyromonas gingivalis (P.gingivalis) is a well-known
      pathogen in periodontitis. This study investigated the pathogenic effects of
      P.gingivalis on autoimmune arthritis in vivo. Collagen-induced arthritis (CIA)
      mice were intraperitoneally injected with W83 and 2561 strains of P.gingivalis.
      Infection with P.gingivalis exacerbated arthritis score in CIA mice. Synovial
      inflammation and bone destruction in CIA mice infected with P.gingivalis were
      more severe than in uninfected CIA mice. Both W83 and 2561 strains were more pro
      arthritic after arthritis symptom was fully activated. Interestingly, only W83
      strain was arthritogenic before autoimmune reaction initiated. Citrullination was
      detected in synovial tissue of CIA mice and CIA mice inoculated with
      P.gingivalis, but not in normal control mice. The citrullinated area was greater
      in P.gingivalis-infected CIA mice than in non-infected CIA mice. This study
      showed that P.gingivalis exacerbated disease in a mouse model of autoimmune
      arthritis and increased the expression of citrullinated antigens in the synovium.
      The arthritogenic effects of P.gingivalis were at least in part, dependent upon
      the bacterial strain with or without fimbriae expression, route and time of
      infection. P.gingivalis-mediated citrullination may explain the possible link
      between periodontal disease and RA.

PMID- 29190707
TI  - Hypofractionated stereotactic boost in intermediate risk prostate carcinoma:
      Preliminary results of a multicenter phase II trial (CKNO-PRO).
AB  - PURPOSE: Dose escalation may improve curability in intermediate-risk prostate
      carcinoma. A multicenter national program was developed to assess toxicity and
      tumor response with hypofractionated stereotactic boost after conventional
      radiotherapy in intermediate-risk prostate cancer. METHODS AND MATERIAL: Between
      August 2010 and April 2013, 76 patients with intermediated-risk prostate
      carcinoma were included in the study. A first course delivered 46 Gy by IMRT
      (68.4% of patients) or 3D conformal radiotherapy (31.6% of patients). The second
      course delivered a boost of 18 Gy (3x6Gy) within 10 days. Gastrointestinal (GI)
      and genitourinary (GU) toxicities were evaluated as defined by NCI-CTCAE (v4.0).
      Secondary outcome measures were local control, overall and metastasis-free
      survival, PSA kinetics, and patient functional status (urinary and sexual)
      according to the IIEF5 and IPSS questionnaires. RESULTS: The overall treatment
      time was 45 days (median, range 40-55). Median follow-up was 26.4 months (range,
      13.6-29.9 months). Seventy-seven per cent (n = 58) of patients presented a
      Gleason score of 7. At 24 months, biological-free survival was 98.7% (95% CI,
      92.8-99.9%) and median PSA 0.46 ng/mL (range, 0.06-6.20 ng/mL). Grade >=2 acute
      GI and GU toxicities were 13.2% and 23.7%, respectively. Grade >=2 late GI and GU
      toxicities were observed in 6.6% and 2.6% of patients, respectively. No grade 4
      toxicity was observed. CONCLUSIONS: Hypofractionated stereotactic boost is
      effective and safely delivered for intermediate-risk prostate carcinoma after
      conventional radiation. Mild-term relapse-free survival and tolerance results are
      promising, and further follow-up is warranted to confirm the results at long
      term. TRIAL REGISTRATION: ClinicalTrials.gov NCT01596816.

PMID- 29190708
TI  - Human mobility prediction from region functions with taxi trajectories.
AB  - People in cities nowadays suffer from increasingly severe traffic jams due to
      less awareness of how collective human mobility is affected by urban planning.
      Besides, understanding how region functions shape human mobility is critical for
      business planning but remains unsolved so far. This study aims to discover the
      association between region functions and resulting human mobility. We establish a
      linear regression model to predict the traffic flows of Beijing based on the
      input referred to as bag of POIs. By solving the predictor in the sense of sparse
      representation, we find that the average prediction precision is over 74% and
      each type of POI contributes differently in the predictor, which accounts for
      what factors and how such region functions attract people visiting. Based on
      these findings, predictive human mobility could be taken into account when
      planning new regions and region functions.

PMID- 29190709
TI  - Relative muscle mass and the risk of incident type 2 diabetes: A cohort study.
AB  - AIMS: The association between relative muscle mass (RMM) and incidence of type 2
      diabetes (T2DM) is largely unknown. We examined whether RMM predicted development
      of T2DM in an apparently young healthy population. METHODS: This cohort study was
      comprised of 113,913 men and 89,854 women, free of T2DM at baseline, who
      underwent a health checkup examination and were followed-up annually or
      biennially for an average of 2.9 years. We used skeletal muscle mass index (SMI)
      as an indicator of RMM. SMI (%) [total skeletal muscle mass (kg)/body weight
      (kg)*100] was estimated using a bioelectrical impedance analyzer. The study
      outcome was incident T2DM, defined as fasting serum glucose >=126 mg/dL, HbA1C
      >=6.5%, or use of medication for T2DM. RESULTS: During 589,098.8 person-years of
      follow-up, 4,264 individuals developed T2DM (incidence rate, 7.2 per 1000 person
      years). Median age (range) at baseline was 39.1 years (18.1-87.1). RMM was
      negatively associated with incidence of T2DM in a dose-response manner. The
      multivariate-adjusted hazard ratios (95% CIs) for incident T2DM comparing
      quartiles 3, 2 and 1 of RMM to the highest quartile were 1.32 (1.14-1.52), 1.63
      (1.42-1.86), and 2.21 (1.94-2.51), respectively, for males and 1.18 (0.88-1.58),
      1.46 (1.11-1.91), and 1.96 (01.51-2.53) for females (P for trend <0.001; 0.011).
      This association was stronger in younger or premenopausal subjects. CONCLUSIONS:
      RMM was negatively associated with development of T2DM in a large sample of young
      and middle-aged Korean adults. Further research is required to determine whether
      preservation of muscle mass through intervention affects the risk of T2DM.

PMID- 29190710
TI  - The association between depressive symptoms and insulin resistance, inflammation
      and adiposity in men and women.
AB  - INTRODUCTION: Depression has been shown to be associated with elevated leptin
      levels, low-grade inflammation and insulin resistance. These derangements are
      often measured in mixed gender cohorts despite the different body compositions
      and hormonal environments of men and women and gender-specific prevalence and
      responses to depression. METHODS: A cross-sectional analysis was carried out on a
      cohort of 639 participants from the ADDITION-Leicester dataset to assess
      differences in markers of diabetes risk, cardiovascular risk and inflammation in
      depressed and non-depressed individuals. Depressive symptoms were determined
      using the WHO (Five) well-being index. Multivariate linear and logistic
      regression analyses were adjusted for age, sex, ethnicity, body mass index,
      smoking, social deprivation and activity levels for continuous and binary
      variables respectively. Further analysis included stratifying the data by gender
      as well as assessing the interaction between depression and gender by including
      an interaction term in the model. RESULTS: Women with depressive symptoms had a
      5.3% larger waist circumference (p = 0.003), 28.7% higher HOMA IR levels (p =
      0.026), 6.6% higher log-leptin levels (p = 0.01) and 22.37% higher TNF-alpha
      levels (p = 0.015) compared with women without. Conversely, depressive symptoms
      in men were associated with 7.8% lower body fat % (p = 0.015) but 48.7% higher
      CRP levels (p = 0.031) compared to men without. However, interaction analysis
      failed to show a significant difference between men and women. CONCLUSIONS:
      Depressive symptoms are associated with metabolic derangements. Whilst women
      tended to show elevations in biomarkers related to an increased risk of type 2
      diabetes (HOMA IR, leptin and TNF-alpha), men showed a marked increase in the
      cardiovascular disease risk biomarker CRP. However, perhaps due to the cohort
      size, interaction analysis did not show a significant gender difference.

PMID- 29190711
TI  - Engineering substrate promiscuity in halophilic alcohol dehydrogenase (HvADH2) by
      in silico design.
AB  - An alcohol dehydrogenase from the halophilic archaeon Haloferax volcanii (HvADH2)
      has been engineered by rational design to broaden its substrate scope towards the
      conversion of a range of aromatic substrates, including flurbiprofenol, that is
      an intermediate of the non-steroidal anti-inflammatory drug, flurbiprofen. Wild
      type HvADH2 showed minimal activity with flurbiprofenol (11.1 mU/mg). A homology
      model of HvADH2 was built and docking experiments with this substrate revealed
      that the biphenyl rings of flurbiprofenol formed strong interactions with
      residues F85 and F108, preventing its optimal binding in the active site.
      Mutations at position 85 however did not increase activity. Site directed
      mutagenesis at position F108 allowed the identification of three variants showing
      a significant (up to 2.3-fold) enhancement of activity towards flurbiprofenol,
      when compared to wild-type HvADH2. Interestingly, F108G variant did not show the
      classic inhibition in the presence of (R)-enantiomer when tested with rac-1
      phenylethanol, underling its potential in racemic resolution of secondary
      alcohols.

PMID- 29190712
TI  - Replication capacity and adaptability of a severe fever with thrombocytopenia
      syndrome virus at different temperatures.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease caused
      by the SFTS virus (SFTSV). Although fever and thrombocytopenia are the typical
      manifestations of SFTS, a specific SFTS case with no fever was observed in
      Zhejiang, China. In this report, we aimed to explore the probable reason for the
      absence of fever by analyzing the genetic characteristics and temperature
      sensitivity (ts) of the SFTSV strain ZJ2013-06, which was isolated from the
      specific case. Phylogenetically, different clusters of SFTSV strains circulated
      in Zhejiang. ZJ2013-06 was farthest from ZJ2014-02, an isolate belonging to a
      Chinese dominant cluster, and nearest to the coastal strain NB24/CHN/2013. Ts
      tests, performed on Vero cells at 37 degrees C and 39 degrees C, indicated that
      ZJ2013-06 had restricted replication at 39 degrees C. Its viral loads were
      substantially reduced at 39 degrees C compared with that at 37 degrees C
      (approximately 100-fold reduction) and were significantly lower than that of
      ZJ2014-02 at 39 degrees C (P < 0.01). By adaptive culture at 39 degrees C, the
      induced strain ZJ2013-06-P7 was obtained. Owing to a reverse mutation (S1616),
      ZJ2013-06-P7 lost the ts of the original strain, displaying similar replication
      processes with NB24/CHN/2013. The results indicated that the amino acid residue
      1616 was related to the ts characteristics of ZJ2013-06. Our study revealed that
      ZJ2013-06 was temperature-sensitive and may be related to the absence of fever in
      our case.

PMID- 29190713
TI  - Operational evaluation of rapid diagnostic testing for Ebola Virus Disease in
      Guinean laboratories.
AB  - BACKGROUND: Rapid Diagnostic Tests (RDTs) for Ebola Virus Disease (EVD) at the
      point of care have the potential to increase access and acceptability of EVD
      testing and the speed of patient isolation and secure burials for suspect cases.
      A pilot program for EVD RDTs in high risk areas of Guinea was introduced in
      October 2015. This paper presents concordance data between EVD RDTs and PCR
      testing in the field as well as an assessment of the acceptability, feasibility,
      and quality assurance of the RDT program. METHODS AND FINDINGS: Concordance data
      were compiled from laboratory surveillance databases. The operational measures of
      the laboratory-based EVD RDT program were evaluated at all 34 sentinel sites in
      Guinea through: (1) a technical questionnaire filled by the lab technicians who
      performed the RDTs, (2) a checklist filled by the evaluator during the site
      visits, and (3) direct observation of the lab technicians performing the quality
      control test. Acceptability of the EVD RDT was good for technicians, patients,
      and families although many technicians (69.8%) expressed concern for their safety
      while performing the test. The feasibility of the program was good based on
      average technician knowledge scores (6.6 out of 8) but basic infrastructure,
      equipment, and supplies were lacking. There was much room for improvement in
      quality assurance of the program. CONCLUSIONS: The implementation of new
      diagnostics in weak laboratory systems requires general training in quality
      assurance, biosafety and communication with patients in addition to specific
      training for the new test. Corresponding capacity building in terms of basic
      equipment and a long-term commitment to transfer supervision and quality
      improvement to national public health staff are necessary for successful
      implementation.

PMID- 29190714
TI  - Biomarkers of IgA vasculitis nephritis in children.
AB  - Henoch-Schonlein purpura is a systemic vasculitis characterized by IgA deposits,
      which target the skin, joints, and kidneys, among other organs. In children,
      prognosis is often good but little is known about biomarkers of pediatric
      nephritis. We hypothesized that biological markers, including cytokines,
      immunoglobulins, IgA-immune complexes, IgA glycosylation and neutrophil
      gelatinase-associated lipocalin (NGAL), may discriminate IgA vasculitis (IgAV)
      pediatric patients with renal involvement from those without renal involvement.
      Fifty children at the time of IgAV rash between 2010 and 2015 were prospectively
      enrolled and compared to 21 controls. All patients were assessed for clinical and
      biological parameters at the time of diagnosis, including the levels of
      cytokines, immunoglobulins, immune complexes, IgA glycosylation and NGAL in serum
      and urine. Among IgAV patients, 33 patients exhibited nephritis (IgAV-N) and 17
      children were without nephritis (IgAV-woN). The serum level of galactose
      deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL
      6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were
      higher in the IgAV-N patients than in the IgAV-woN patients. Among those markers,
      urinary IgA and IgM had the highest AUC (0.86 and 0.87 respectively, p<0.0001).
      This prospective cohort study furthers our understanding of the pathophysiology
      of IgAV. We identified biomarkers that are able to distinguish patients initially
      with or without nephritis. To conclude, serum Gd-IgA1 and urinary IgA, IgG, IgM,
      IL-6, IL-8, IL-10, and IgA-IgG and IgA-sCD89 complexes could identify IgAV
      pediatric patients with renal involvement at the time of diagnosis.

PMID- 29190715
TI  - A history of repetitive cesarean section is a risk factor of anemia in healthy
      perimenopausal women: The Korea National Health and Nutrition Examination Survey
      2010-2012.
AB  - BACKGROUND AND OBJECTIVES: To determine whether the delivery method is associated
      with the rate of anemia in later life, using the data from the Korea National
      Health and Nutrition Examination Survey (KNHANES). METHODS: This study used data
      from the KNHANES 2010-2012. Among 25,534 participants, 8,126 cases were included
      in this study after exclusion of males and other inappropriate data. The study
      population was divided into three groups according to the delivery modes: vaginal
      delivery (VD) only group, single cesarean delivery (SCD) group and repetitive
      cesarean delivery (RCD) group. The primary outcome was anemia and iron
      deficiency. Anemia was defined as hemoglobin <12 g/dl in accordance with the
      World Health Organization criteria. Iron deficiency was defined as low
      transferrin saturation (TSAT) or ferritin levels. Multivariate analysis was used
      for determination of association between the delivery modes and anemia. RESULTS:
      The mean age was 53.4 years and the median time from the last delivery to the
      survey was 25 years. The VD only group was composed of 6,493 (79.9%) women, while
      685 (8.4%) were classified as the SCD group and 948 (11.7%) were classified as a
      RCD group. The rates of anemia were 11.8%, 13.9%, and 19.7% in VD only group, SCD
      group, and RCD group, respectively. However, those groups were significantly
      different in many confounding factors. Therefore, to adjust those factors,
      multivariate analysis and subgroup analysis were followed. The odds of SCD for
      anemia and iron deficiency were not different from those of VD only. However, RCD
      was independently associated with anemia [Odds ratio(OR) 1.47, 95% Confidence
      interval (CI) 1.21-1.79, P <0.001] and iron deficiency (OR 1.42, 95% CI 1.21
      1.67, P <0.001) compared to VD only. In the subgroup analysis, RCD was
      significantly associated with anemia in perimenopausal women, women with iron
      deficiency, those without any comorbidity and those without anemia-prone
      treatment. CONCLUSION: Repetitive cesarean section may be a risk factor for
      future development of anemia in later life, especially in perimenopausal period.
      Therefore, evaluation and management of anemia in longer postpartum period should
      be considered for women who experience repetitive cesarean section.

PMID- 29190716
TI  - Suppression of cancer stemness by upregulating Ligand-of-Numb protein X1 in
      colorectal carcinoma.
AB  - Cancer stem-like cells (CSCs) have been reported to play major roles in
      tumorigenesis, tumor relapse, and metastasis after therapy against colorectal
      carcinoma (CRC). Therefore, identification of colorectal CSC regulators could
      provide promising targets for CRC. Ligand-of-Numb protein X1 (LNX1) is one E3
      ubiquitin ligase which mediates the ubiquitination and degradation of Numb.
      Although several studies indicate LNX1 could be a potential suppressor of cancer
      diseases, the functions of LNX1 in mediating cancer stemness remain poorly
      understood. In this study, LNX1 was identified as a negative regulator of cancer
      stemness in CRC, which was downregulated in colonospheres or side population (SP)
      cells. Furthermore, the coxsackievirus and adenovirus receptor (CXADR) was found
      to be one critical downstream mediator of cancer stemness regulated by LNX1.
      Interestingly, the anti-breast cancer drug tamoxifen was found to be an agonist
      of LNX1 and suppress cancer stemness in CRC. In sum, this study provided the
      evidences that LNX1 signaling plays important roles in regulating the stemness of
      colon cancer cells.

PMID- 29190717
TI  - Impact of chemotherapy on perceptions related to food intake in women with breast
      cancer: A prospective study.
AB  - Breast cancer (BC) treatment includes mostly chemotherapy (CT), which can cause
      side effects like nausea, taste changes, early satiety, slow gastric emptying and
      xerostomia. In this way, the individual's relationship with food may change
      during the treatment. The aim of this study was to evaluate the impact of
      chemotherapy on perceptions related to food intake of women with BC. Fifty-five
      women with BC were followed, and data were collected at three periods during
      first-line CT: beginning (T0), intermediate (T1) and end (T2). A visual analogue
      scale (VAS) (0 to 10 cm) for hunger, appetite for various food categories and
      meal enjoyment was investigated. The frequency and intensity of side effects were
      evaluated using a 4 cm scale. The results showed a higher prevalence of taste
      changes in T1 (p = 0.044) and more nausea in T1 and T2 (p = 0.018). Furthermore,
      the intensity of nausea was higher in T2 (p = 0.01) than in the other periods. We
      observed moderate hunger in T0, T1 and T2 (p = 0.113), but the overall appetite
      increased between T0 and T2 (p = 0.003). Meal enjoyment was reduced from T0 to
      T1and returned back to the initial value in T2 (p = 0.021). The appetite for
      salty (p = 0.004) and spicy (p = 0.03) foods was increased in T1. There was an
      increase of body weight (p = 0.008), body mass index (BMI) (p = 0.009) and waist
      circumference (WC) (p = 0.03) during CT. CT changes food hedonism, increasing the
      overall appetite and the appetite for salty and spicy foods. Moreover, we
      observed the negative impact of CT on meal enjoyment and an increase in side
      effects and anthropometric parameters.

PMID- 29190718
TI  - Investigating the validity of the DN4 in a consecutive population of patients
      with chronic pain.
AB  - Neuropathic pain is clinically described as pain caused by a lesion or disease of
      the somatosensory nervous system. The aim of this study was to assess the
      validity of the Dutch version of the DN4, in a cross-sectional multicentre
      design, as a screening tool for detecting a neuropathic pain component in a large
      consecutive, not pre-stratified on basis of the target outcome, population of
      patients with chronic pain. Patients' pain was classified by two independent
      (pain-)physicians as the gold standard. The analysis was initially performed on
      the outcomes of those patients (n = 228 out of 291) in whom both physicians
      agreed in their pain classification. Compared to the gold standard the DN4 had a
      sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview
      items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the
      DN4-signs (three examination items) it was respectively 75% and 75%. In
      conclusion, because it seems that the DN4 helps to identify a neuropathic pain
      component in a consecutive population of patients with chronic pain in a moderate
      way, a comprehensive (physical-) examination by the physician is still obligate.

PMID- 29190719
TI  - Breakfast habits and differences regarding abdominal obesity in a cross-sectional
      study in Spanish adults: The ANIBES study.
AB  - BACKGROUND: Previous studies have indicated that breakfast has a protective
      effect against obesity. The aim of this study was to describe the breakfast
      habits of the Spanish adult population and to assess the possible association
      between breakfast frequency and the presence of abdominal obesity, in a cross
      sectional analysis of the ANIBES Study. METHODS: A representative sample of 1655
      Spanish adults (aged 39+/-12 y; (mean+/-sd)) from the ANIBES Study was
      investigated. The final field work was carried out from mid-September to November
      (three months) 2013. Collected data included a dietary data collected by a 3-days
      food record, and health, socioeconomic, physical activity and anthropometric
      (weight, height and waist circumference) data. Abdominal obesity was defined as
      having a waist-to-height ratio >=0.5. The adults were also classified into three
      groups based on the number of days they ate breakfast (never (0/3 days),
      sometimes (1-2/3 days) and always (3/3 days)). Logistic regression analyses were
      used to evaluate the association between breakfast and abdominal obesity.
      RESULTS: In total, 3.6% of adults skipped breakfast and 14.1% ate breakfast
      sometimes. Having always breakfast was negatively associated with abdominal
      obesity [OR = 0.738 (0.558-0.975) p = 0.033]. The odds of abdominal obesity after
      full adjustment (age, gender, and educational and activity level) were 1.5 times
      higher for those who skipped breakfast when compared to those who always have
      breakfast. By correcting the model considered for other variables, the odds among
      smokers decreased when they have breakfast sometimes [OR = 0.032 (0.003-0.387) p
      = 0.007] and always [OR = 0.023 (0.002-0.270) p = 0.003] comparing with smokers
      who skip breakfast. CONCLUSION: Breakfast frequency could be negatively
      associated with abdominal obesity, especially among smokers.

PMID- 29190720
TI  - Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub
      study of the CENTRAL trial.
AB  - BACKGROUND: Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel
      during exercise and is linked to insulin resistance, but the long-term effect of
      weight loss strategies on IMTG among participants with abdominal fat, remain
      unclear. METHODS: In an 18-month trial, sedentary participants with abdominal
      fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low
      carbohydrate (MED/LC) diet (including 28g.day-1 of walnuts). After 6-months, the
      participants were re-randomized to moderate intense physical activity (PA+) or
      non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to
      quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats.
      RESULTS: Across the 277 participants [86% men, age = 48 years, body-mass-index
      (BMI) = 31kg/m2, visceral fat = 33%] 86% completed the 18-m trial. At baseline,
      women had higher IMTG than men (3.4% vs. 2.3%, p<0.001) and increased IMTG was
      associated with aging and higher BMI, visceral and intermuscular fats, HbA1c%,
      HDL-c and leptin(p<0.05), but not with intra-hepatic fat. After 18 month of
      intervention and a -3 kg mean weight loss, participants significantly increased
      IMTG by 25%, with a distinct effect in the MED/LCPA+ group as compared to the
      other intervention groups (57% vs. 9.5-18.5%, p<0.05). Changes in IMTG were
      associated with visceral and intermuscular fat, metabolic syndrome, insulin and
      leptin (p<0.05 for all), however, these associations did not remain after
      adjustment for visceral fat changes. CONCLUSIONS: Lifestyle strategies
      differentially affect IMTG accumulation; combination of exercise with decreased
      carbohydrate/increased unsaturated fat proportion intake greatly increase IMTG.
      Our findings suggest that increased IMTG during diet-induced moderate weight loss
      may not be directly related to cardiometabolic risk. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01530724.

PMID- 29190721
TI  - Carriage of Staphylococcus aureus among Portuguese nursing students: A
      longitudinal cohort study over four years of education.
AB  - BACKGROUND: Staphylococcus aureus is a major human pathogen that can colonize
      healthy people mainly in the anterior nares. The aim of the present study was to
      evaluate S. aureus nasal colonization over time among Portuguese nursing
      students, including methicillin-resistant S. aureus (MRSA). METHODS AND FINDINGS:
      In this longitudinal cohort study, we collected 280 nasal swabs from nursing
      students at 14 time points over four years of schooling (2012-2016). The isolates
      were characterized by pulsed-field gel electrophoresis (PFGE), spa typing,
      multilocus sequence typing (MLST), and SCCmec typing for MRSA. Among 47 students,
      20 (43%) carried methicillin-susceptible S. aureus (MSSA) at admission, but none
      was colonized with MRSA. A total of 19 students (40%) became colonized after
      exposure during the nursing training, out of which five carried MRSA. Overall, 39
      students (83%) had S. aureus detected at least once during the study period.
      Among the 97 MSSA isolates, most (65%) belonged to four clones: PFGE A-ST30
      (21%), B-ST72 (20%), C-ST508 (13%), and D-ST398 (11%). Three of the five MRSA
      carriers were colonized with the predominant clone circulating in Portuguese
      hospitals (ST22-IVh) and two with ST3162-II. Colonization of nursing students was
      highly dynamic with continuous appearance of strains with distinct PFGE types in
      the same individual. CONCLUSIONS: A considerable proportion of students became
      colonized by S. aureus, including MRSA, during the nursing education, evidencing
      this population represents an important reservoir of S. aureus. Therefore,
      education on infection control measures in nursing schools is of major
      importance.

PMID- 29190722
TI  - Association between grip strength and hand and knee radiographic osteoarthritis
      in Korean adults: Data from the Dong-gu study.
AB  - OBJECTIVES: We assessed whether grip strength was related to various types of
      radiographic damage in Korean adults with osteoarthritis (OA). METHODS: Data from
      2,251 subjects enrolled in the Dong-gu study, who had no hand joint pain, were
      analyzed to investigate the relationship between grip strength and OA. Hand grip
      strength was measured using a hand-held dynamometer, and radiographs of the hand
      and knee were scored according to a semi-quantitative grading system. Multiple
      linear regressions were used to explore associations between grip strength and
      radiographic features of OA. RESULTS: Grip strength in men and women was
      negatively related to hand (both p < 0.001) and knee (men, p < 0.001; women, p =
      0.010) OA after adjusting for confounders. Hand (men, p < 0.001; women, p =
      0.001) and knee (both p < 0.001) joint space narrowing (JSN) showed the strongest
      associations with low grip strength, regardless of gender. Moreover, the severity
      of hand osteophytes in women (p = 0.001), and subchondral cysts (men, p < 0.001)
      was correlated with low grip strength in both genders. CONCLUSIONS: Among
      subjects without hand joint pain, low grip strength was associated significantly
      with hand and knee radiographic OA, regardless of gender. Among all types of OA
      radiographic damage, low grip strength showed the strongest association with JSN.

PMID- 29190723
TI  - Effects of increasing temperature and, CO2 on quality of litter, shredders, and
      microorganisms in Amazonian aquatic systems.
AB  - Climate change may affect the chemical composition of riparian leaf litter and,
      aquatic organisms and, consequently, leaf breakdown. We evaluated the effects of
      different scenarios combining increased temperature and carbon dioxide (CO2) on
      leaf detritus of Hevea spruceana (Benth) Mull. and decomposers (insect shredders
      and microorganisms). We hypothesized that simulated climate change (warming and
      elevated CO2) would: i) decrease leaf-litter quality, ii) decrease survival and
      leaf breakdown by shredders, and iii) increase microbial leaf breakdown and
      fungal biomass. We performed the experiment in four microcosm chambers that
      simulated air temperature and CO2 changes in relation to a real-time control
      tracking current conditions in Manaus, Amazonas, Brazil. The experiment lasted
      seven days. During the experiment mean air temperature and CO2 concentration
      ranged from 26.96 +/- 0.98oC and 537.86 +/- 18.36 ppmv in the control to 31.75 +/
      0.50oC and 1636.96 +/- 17.99 ppmv in the extreme chamber, respectively. However,
      phosphorus concentration in the leaf litter decreased with warming and elevated
      CO2. Leaf quality (percentage of carbon, nitrogen, phosphorus, cellulose and
      lignin) was not influenced by soil flooding. Fungal biomass and microbial leaf
      breakdown were positively influenced by temperature and CO2 increase and reached
      their highest values in the intermediate condition. Both total and shredder leaf
      breakdown, and shredder survival rate were similar among all climatic conditions.
      Thus, low leaf-litter quality due to climate change and higher leaf breakdown
      under intermediate conditions may indicate an increase of riparian metabolism due
      to temperature and CO2 increase, highlighting the risk (e.g., decreased
      productivity) of global warming for tropical streams.

PMID- 29190724
TI  - Socioeconomic characterization of regions through the lens of individual
      financial transactions.
AB  - People are increasingly leaving digital traces of their daily activities through
      interacting with their digital environment. Among these traces, financial
      transactions are of paramount interest since they provide a panoramic view of
      human life through the lens of purchases, from food and clothes to sport and
      travel. Although many analyses have been done to study the individual preferences
      based on credit card transaction, characterizing human behavior at larger scales
      remains largely unexplored. This is mainly due to the lack of models that can
      relate individual transactions to macro-socioeconomic indicators. Building these
      models, not only can we obtain a nearly real-time information about socioeconomic
      characteristics of regions, usually available yearly or quarterly through
      official statistics, but also it can reveal hidden social and economic structures
      that cannot be captured by official indicators. In this paper, we aim to
      elucidate how macro-socioeconomic patterns could be understood based on
      individual financial decisions. To this end, we reveal the underlying
      interconnection of the network of spending leveraging anonymized individual
      credit/debit card transactions data, craft micro-socioeconomic indices that
      consists of various social and economic aspects of human life, and propose a
      machine learning framework to predict macro-socioeconomic indicators.

PMID- 29190725
TI  - Modelling the effects of quadrivalent Human Papillomavirus (HPV) vaccination in
      Puerto Rico.
AB  - BACKGROUND: No study has estimated the potential impact of Human Papillomavirus
      (HPV) vaccination in Puerto Rico, a population with considerable burden of HPV
      related morbidities. We evaluated the health and economic impacts of implementing
      a vaccination strategy for females and males in Puerto Rico, with the
      quadrivalent HPV (HPV4) vaccine, under different vaccination scenarios. METHODS:
      We adapted a mathematical model which estimates the direct and indirect health
      benefits and costs of HPV4 vaccination in a dynamic population. The model
      compared three vaccination scenarios against screening only (no-vaccination) for
      three doses of HPV4 vaccine among individuals aged 11-15 years in Puerto Rico: 1)
      34% for females and 13% for males (34%F/13%M), 2) 50% for females and 40% for
      males (50%F/40%M), and 3) 80% for female and 64% for male (80%F/64%M). Data
      specific to Puerto Rico was used. When not available, values from the United
      States were used. Input data consisted of demographic, behavioral,
      epidemiological, screening, and economic parameters. RESULTS: The model predicted
      decreases in: 1) HPV infection prevalence for females and males, 2) cervical
      intraepithelial neoplasia and cervical cancer incidence for females, 3) genital
      warts incidence for females and males, and 4) cervical cancer deaths among
      females, when various vaccination program scenarios were considered. In addition,
      when the vaccination percentage was increased in every scenario, the reduction
      was greater and began earlier. The analysis also evidenced an incremental cost
      effectiveness ratio (ICER) of $1,964 per quality-adjusted life year gained for
      the 80%F/64%M uptake scenario. CONCLUSIONS: HPV vaccine can prove its cost
      effectiveness and substantially reduce the burden and costs associated to various
      HPV-related conditions when targeted to the adequate population together with an
      organized HPV vaccination program.

PMID- 29190726
TI  - Socio-demographic, health-related, and individual correlates of diagnostic self
      testing by lay people: Results from a representative survey in Germany.
AB  - INTRODUCTION: A broad range of self-tests (testing for e.g. HIV, cancer,
      hepatitis B/C) have become available and can be conducted by lay consumers
      without the help of a health professional. The aims of this study were to (a)
      investigate the prevalence of self-testing, (b) identify the most frequently used
      self-tests, and (c) explore the associations between socio-demographic, health
      related and individual factors with self-testing. METHODS: A face-to-face plus
      paper-pencil cross-sectional survey was conducted. The sample consisted of 2.527
      respondents who were representative of the German population in terms of the age,
      sex, and residence. Basic descriptive statistics and univariate logistic
      regression analyses were performed. RESULTS: 8.5% of the participants reported
      having used one or more self-tests in the past, totalling 363 self-tests, with a
      mean of 1.7 (min. = 1, max. = 6). The three self-tests most frequently indicated
      were for detecting diabetes, bowel cancer, and allergies. Self-testers were older
      (Nagelkerke R2 = .006, p < .01), had a higher BMI (Nagelkerke R2 = .013, p <
      .001) and displayed more physical and mental fatigue (Nagelkerke R2 = .031, p <
      .001) than non-testers. Self-testers also reported higher global life
      satisfaction values (Nagelkerke R2 = .008, p < .01) and a higher educational
      level (Nagelkerke R2 = .015, p < .01). CONCLUSIONS: Self-testing is fairly
      prevalent in Germany Given the current shortage of physicians in Germany,
      especially in rural areas, and recent studies on the use of self-medication, the
      topic of self-testing has a great practical and socio-political relevance. Future
      studies should investigate further predictors of self-testing (e.g. contextual,
      situational and individual factors) as well as the emotional consequences of
      testing as a layperson without the attendance of a health professional.

PMID- 29190727
TI  - Influence of the type of training task on intermanual transfer effects in upper
      limb prosthesis training: A randomized pre-posttest study.
AB  - Intermanual transfer, the transfer of motor skills from the trained hand to the
      untrained hand, can be used to train upper limb prosthesis skills. The aim of
      this study was to determine the relation between the magnitude of the intermanual
      transfer effect and the type of training task. The used tasks were based on
      different aspects of prosthetic handling: reaching, grasping, grip-force
      production and functional tasks. A single-blinded clinical trial, with a pre
      posttest design was executed. Seventy-one able-bodied, right-handed participants
      were randomly assigned to four training and two control groups. The training
      groups performed a training program with an upper-limb prosthesis simulator. One
      control group performed a sham training (a dummy training without the prosthesis
      simulator) and another control group received no training at all. The training
      groups and sham group trained on five consecutive days. To determine the
      improvement in skills, a test was administered before, immediately after, and one
      week after the training. Training was performed with the 'unaffected' arm; tests
      were performed with the 'affected' arm, with the latter resembling the amputated
      limb. In this study half of the participants trained with the dominant hand,
      while the other half trained with the non-dominant hand. Participants executed
      four tests that corresponded to the different training tasks. The tests measured
      the reaching (movement time and symmetry ratio), grasping (opening time, duration
      of maximum hand opening, and closing time), grip-force production (deviation of
      asked grip-force) and functional (movement time) performance. Half of the
      participants were tested with their dominant arm and half of the participants
      with their non-dominant arm. Intermanual transfer effects were not found for
      reaching, grasping or functional tasks. However, we did find intermanual transfer
      effects for grip-force production tasks. Possibly, the study design contributed
      to the negative results due to the duration of the training sessions and test
      sessions. The positive results of the grip-force production might be an effect of
      the specificity of the training, that was totally focused on training grip-force
      production. When using intermanual transfer training in novice amputees, specific
      training should be devoted to grip-force.

PMID- 29190728
TI  - Chagas disease vector control and Taylor's law.
AB  - BACKGROUND: Large spatial and temporal fluctuations in the population density of
      living organisms have profound consequences for biodiversity conservation, food
      production, pest control and disease control, especially vector-borne disease
      control. Chagas disease vector control based on insecticide spraying could
      benefit from improved concepts and methods to deal with spatial variations in
      vector population density. METHODOLOGY/PRINCIPAL FINDINGS: We show that Taylor's
      law (TL) of fluctuation scaling describes accurately the mean and variance over
      space of relative abundance, by habitat, of four insect vectors of Chagas disease
      (Triatoma infestans, Triatoma guasayana, Triatoma garciabesi and Triatoma
      sordida) in 33,908 searches of people's dwellings and associated habitats in 79
      field surveys in four districts in the Argentine Chaco region, before and after
      insecticide spraying. As TL predicts, the logarithm of the sample variance of bug
      relative abundance closely approximates a linear function of the logarithm of the
      sample mean of abundance in different habitats. Slopes of TL indicate spatial
      aggregation or variation in habitat suitability. Predictions of new mathematical
      models of the effect of vector control measures on TL agree overall with field
      data before and after community-wide spraying of insecticide.
      CONCLUSIONS/SIGNIFICANCE: A spatial Taylor's law identifies key habitats with
      high average infestation and spatially highly variable infestation, providing a
      new instrument for the control and elimination of the vectors of a major human
      disease.

PMID- 29190729
TI  - Increased MMAB level in mitochondria as a novel biomarker of hepatotoxicity
      induced by Efavirenz.
AB  - BACKGROUND: Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor
      (NNRTI), has been widely used in the therapy of human immunodeficiency virus
      (HIV) infection. Some of its toxic effects on hepatic cells have been reported to
      display features of mitochondrial dysfunction through bioenergetic stress and
      autophagy, etc. However, alteration of protein levels, especially mitochondrial
      protein levels, in hepatic cells during treatment of EFV has not been fully
      investigated. METHODS: We built a cell model of EFV-induced liver toxicity
      through treating Huh-7 cells with different concentrations of EFV for different
      time followed by the analysis of cell viability using cell counting kit -8 (CCK8)
      and reactive oxygen species (ROS) using 2',7'-dichlorodihydrofluorescein
      diacetate (DCFH-DA) and MitoSox dye. Proteomic profiles in the mitochondria of
      Huh-7 cells stimulated by EFV were analyzed. Four differentially expressed
      proteins were quantified by real time RT-PCR. We also detected the expression of
      mitochondrial precursor Cob(I)yrinic acid a,c-diamide adenosyltransferase (MMAB)
      by immunohistochemistry analysis in clinical samples. The expression levels of
      MMAB and ROS were detected in EFV-treated Huh-7 cells with and without shRNA used
      to knock down MMAB, and in primary hepatocytes (PHC). The effects of other anti
      HIV drugs (nevirapine (NVP) and tenofovirdisoproxil (TDF)), and hydrogen peroxide
      (H2O2) were also tested. Amino acid analysis and fatty aldehyde dehydrogenase
      (ALDH3A2) expression after MMAB expression knock-down with shRNA was used to
      investigate the metabolic effect of MMAB in Huh-7 cells. RESULTS: EFV treatment
      inhibited cell viability and increased ROS production with time- and
      concentration-dependence. Proteomic study was performed at 2 hours after EFV
      treatment. After treated Huh-7 cells with EFV (2.5mg/L or 10 mg/L) for 2 h,
      fifteen differentially expressed protein spots from purified mitochondrion that
      included four mitochondria proteins were detected in EFV-treated Huh-7 cells
      compared to controls. Consistent with protein expression levels, mRNA expression
      levels of mitochondrial protein MMAB were also increased by EFV treatment. In
      addition, the liver of EFV-treated HIV infected patients showed substantially
      higher levels of MMAB expression compared to the livers of untreated or protease
      inhibitor (PI)-treated HIV-infected patients. Furthermore, ROS were found to be
      decreased in Huh-7 cells treated with shMMAB compared with empty plasmid treated
      with EFV at the concentration of 2.5 or 10 mg/L. MMAB was increased in EFV
      treated Huh-7 cells and primary hepatocytes. However, no change in MMAB
      expression was detected after treatment of Huh-7 cells and primary hepatocytes
      with anti-HIV drugs nevirapine (NVP) and tenofovirdisoproxil (TDF), or hydrogen
      peroxide (H2O2), although ROS was increased in these cells. Finally, knockdown of
      MMAB by shRNA induced increases in the beta-Alanine (beta-Ala) production levels
      and decrease in ALDH3A2 expression. CONCLUSIONS: A mitochondrial proteomic study
      was performed to study the proteins related to EFV-inducted liver toxicity. MMAB
      might be a target and potential biomarker of hepatotoxicity in EFV-induced liver
      toxicity.

PMID- 29190730
TI  - Increased levels of plasma total tau in adult Down syndrome.
AB  - Down syndrome (DS) is the most prevalent chromosomal abnormality. Early-onset
      dementia with the pathology of Alzheimer's disease (AD) frequently develops in
      DS. Reliable blood biomarkers are needed to support the diagnosis for dementia in
      DS, since positron emission tomography or cerebrospinal fluid sampling is
      burdensome, particularly for patients with DS. Plasma t-tau is one of the
      established biomarkers for the diagnosis of AD, suggesting the potential value of
      t-tau as a biomarker for dementia in DS. The aim of this study was to assess and
      compare plasma levels of t-tau in adults with DS and in an age-matched control
      population. In this study, plasma levels of t-tau in 21 patients with DS and 22
      control participants were measured by an ultrasensitive immunoassay technology,
      the single-molecule immunoarray (Simoa) method. We observed significantly
      increased plasma t-tau levels in the DS group (mean +/- standard deviation (SD) =
      0.643+/-0.493) compared to those in the control group (mean +/- SD = 0.470+/
      0.232): P = 0.0050. Moreover, age dependent correlation of plasma t-tau was only
      found in the DS group, and not in the control group. These findings suggest that
      elevated plasma t-tau levels reflect AD pathology and therefore have potential as
      an objective biomarker to detect dementia in adult DS.

PMID- 29190731
TI  - Newly identified risk factors for MRSA carriage in The Netherlands.
AB  - OBJECTIVES: To elucidate new risk factors for MRSA carriers without known risk
      factors (MRSA of unknown origin; MUO). These MUO carriers are neither pre
      emptively screened nor isolated as normally dictated by the Dutch Search &
      Destroy policy, thus resulting in policy failure. METHODS: We performed a
      prospective case control study to determine risk factors for MUO
      acquisition/carriage (Dutch Trial Register: NTR2041). Cases were MUO carriers
      reported by participating medical microbiological laboratories to the RIVM from
      September 1st 2011 until September 1st 2013. Controls were randomly selected from
      the community during this period. RESULTS: Significant risk factors for MUO in
      logistic multivariate analysis were antibiotic use in the last twelve months, aOR
      8.1 (5.6-11.7), screened as contact in a contact tracing but not detected as a
      MRSA carrier at that time, aOR 4.3 (2.1-8.8), having at least one foreign parent,
      aOR 2.4 (1.4-3.9) and receiving ambulatory care, aOR 2.3 (1.4-3.7). Our found
      risk factors explained 83% of the MUO carriage. CONCLUSIONS: Identifying new risk
      factors for MRSA carriers remains crucial for countries that apply a targeted
      screening approach as a Search and Destroy policy or as vertical infection
      prevention measure.

PMID- 29190732
TI  - Xuezhikang, an extract from red yeast rice, attenuates vulnerable plaque
      progression by suppressing endoplasmic reticulum stress-mediated apoptosis and
      inflammation.
AB  - Xuezhikang (XZK), an extract of red yeast rice, is a traditional Chinese medicine
      widely used for the treatment of cardiovascular diseases in China and other
      countries. However, whether XZK treatment can improve atherosclerotic plaque
      stability is not fully understood. Based on our previously developed mouse model
      of spontaneous vulnerable plaque formation and rupture in carotid arteries in
      ApoE-/- mice. We showed that low-dose (600 mg/kg/d) XZK improved plaque stability
      without decreasing plaque area, whereas high-dose (1200 mg/kg/d) XZK dramatically
      inhibited vulnerable plaque progression accompanied by decreased plaque area.
      Mechanistically, XZK significantly suppressed lesional endoplasmic reticulum (ER)
      stress in mouse carotid arteries. In vitro, XZK inhibited 7-KC-induced activation
      of ER stress in RAW264.7 macrophages, as assessed by the reduced levels of p
      PERK, p-IRE1alpha, p-eIF2alpha, c-ATF6, s-XBP1, and CHOP. Compared to controls,
      the XZK-treated group displayed dramatically decreased apoptotic cell numbers
      (shown by decreased TUNEL- and cleaved caspase3-positive cells), lower necrotic
      core area and ratio, and reduced expression of NF-kappaB target gene. In RAW264.7
      cells, XZK inhibited 7-KC-induced upregulation of apoptosis, protein expression
      of apoptotic markers (cleaved caspase-3 and cleaved PARP), and NF-kappaB
      activation (shown by target gene transcription and IkappaBalpha reduction).
      Collectively, our results suggest that XZK effectively suppresses vulnerable
      plaque progression and rupture by mitigating macrophage ER stress and
      consequently inhibiting apoptosis and the NF-kappaB pro-inflammatory pathway,
      thereby providing an alternative therapeutic strategy for stabilizing
      atherosclerotic plaques.

PMID- 29190733
TI  - The end of HIV: Still a very long way to go, but progress continues.
AB  - In an Editorial accompanying PLOS Medicine's Special Issue on Advances in
      Prevention, Treatment and Cure of HIV/AIDS, Guest Editors Steven Deeks, Sharon
      Lewin, and Linda-Gail Bekker discuss priorities in the field and the content of
      the issue.

PMID- 29190734
TI  - A novel Porphyromonas gingivalis enzyme: An atypical dipeptidyl peptidase III
      with an ARM repeat domain.
AB  - Porphyromonas gingivalis, an asaccharolytic Gram-negative oral anaerobe, is a
      major pathogen associated with adult periodontitis, a chronic infective disease
      that a significant percentage of the human population suffers from. It
      preferentially utilizes dipeptides as its carbon source, suggesting the
      importance of dipeptidyl peptidase (DPP) types of enzyme for its growth. Until
      now DPP IV, DPP5, 7 and 11 have been extensively investigated. Here, we report
      the characterization of DPP III using molecular biology, biochemical, biophysical
      and computational chemistry methods. In addition to the expected evolutionarily
      conserved regions of all DPP III family members, PgDPP III possesses a C-terminal
      extension containing an Armadillo (ARM) type fold similar to the AlkD family of
      bacterial DNA glycosylases, implicating it in alkylation repair functions.
      However, complementation assays in a DNA repair-deficient Escherichia coli strain
      indicated the absence of alkylation repair function for PgDPP III. Biochemical
      analyses of recombinant PgDPP III revealed activity similar to that of DPP III
      from Bacteroides thetaiotaomicron, and in the range between activities of human
      and yeast counterparts. However, the catalytic efficiency of the separately
      expressed DPP III domain is ~1000-fold weaker. The structure and dynamics of the
      ligand-free enzyme and its complex with two different diarginyl arylamide
      substrates was investigated using small angle X-ray scattering, homology
      modeling, MD simulations and hydrogen/deuterium exchange (HDX). The correlation
      between the experimental HDX and MD data improved with simulation time,
      suggesting that the DPP III domain adopts a semi-closed or closed form in
      solution, similar to that reported for human DPP III. The obtained results reveal
      an atypical DPP III with increased structural complexity: its superhelical C
      terminal domain contributes to peptidase activity and influences DPP III
      interdomain dynamics. Overall, this research reveals multifunctionality of PgDPP
      III and opens direction for future research of DPP III family proteins.

PMID- 29190735
TI  - Subgroup analysis of continuous renal replacement therapy in severely burned
      patients.
AB  - Continuous renal replacement therapy (CRRT) is administered to critically ill
      patients with renal injuries as renal replacement or renal support. We aimed to
      identify predictors of mortality among burn patients receiving CRRT, and to
      investigate clinical differences according to acute kidney injury (AKI) status.
      This retrospective observational study evaluated 216 Korean burn patients who
      received CRRT at a burn intensive care unit. Patients were categorized by AKI
      status. Data were collected regarding arterial pH, laboratory results, ratio of
      arterial oxygen partial pressure to fractional inspired oxygen (PF ratio), and
      urine production. Among surviving patients, CRRT duration and the sequential
      organ failure assessment score were 6.5 days and 4.7 in the non-AKI group and
      23.4 days and 7.4 in the AKI group, respectively (p = 0.003 and p = 0.008). On
      logistic regression analyses, mortality was significantly associated with a pH of
      <7.2 (p = 0.004), potassium levels of >5.0 mEg/L (p = 0.045), creatinine levels
      of >2.0 mg/dL (p = 0.011), lactate levels of >2 mmol/L (p<0.001), a PF ratio of
      <200 (p = 0.042), and a platelet count of <100,000/MUL (p<0.001). In the AKI
      group, poor outcomes were associated with a pH of <7.2, potassium levels of <5.0
      mEg/L, lactate levels of >2 mmol/L, and a platelet count of <100,000/MUL, while
      good outcomes were associated with creatinine levels of >2 mg/dL. In the non-AKI
      group, poor outcomes were associated with lactate levels of >1.5 mmol/L, a PF
      ratio of <200, and a platelet count of <100,000/MUL, while good outcomes were
      associated with creatinine levels of >1.2 mg/dL. Duration of the CRRT application
      and the requirement for either renal replacement or renal support at the
      initiation of CRRT application are important considerations depending on its
      application.

PMID- 29190736
TI  - Humoral immune response against two surface antigens of Chlamydia pecorum in
      vaccinated and naturally infected sheep.
AB  - Chlamydia pecorum is a globally recognised livestock pathogen due to the
      significant clinical and economic impact it poses to livestock producers. Routine
      serological diagnosis is through a complement fixation test (CFT), which is often
      criticised for cross-reactivity, poor sensitivity and specificity. Although
      serology remains the preferred method in veterinary diagnostic laboratories,
      serological assays based on surface antigens of C. pecorum have not been
      established until now. In this study, we evaluated the use of two chlamydial
      recombinant protein antigens (PmpG and MOMP-G) by a direct IgG ELISA method for
      detection of ovine anti-chlamydial antibodies. Using the Pepscan method we then
      identified B cell epitopes across PmpG and MOMP-G proteins, in lambs with (a)
      naturally occurring asymptomatic C. pecorum infections (b) C. pecorum-associated
      polyarthritis and (c) recombinant PmpG and MOMP-G vaccine. Plasma IgG antibodies
      to PmpG in natural infection of lambs were detected earlier in infection than CFT
      and served as an acute phase marker. Antibodies to MOMP-G IgG were significantly
      heightened in lambs with C. pecorum-associated polyarthritis. PmpG and MOMP-G
      specific B-cell epitope mapping revealed epitope responses in immunised lambs
      cluster with some of the epitope responses in naturally infected lambs. B-cell
      epitope mapping further revealed that lambs with polyarthritis recognised several
      unique PmpG (50% frequency, peptide 8, 25, 40, 41 and 50) and MOMP (50%
      frequency, peptide 50) epitopes in comparison to asymptomatic infections. The
      findings of this study will have implications towards improved serodiagnosis of
      C. pecorum infections in livestock and inform the downstream development of
      alternative peptide-based antigens for future C. pecorum vaccine studies.

PMID- 29190737
TI  - A short feature vector for image matching: The Log-Polar Magnitude feature
      descriptor.
AB  - The choice of an optimal feature detector-descriptor combination for image
      matching often depends on the application and the image type. In this paper, we
      propose the Log-Polar Magnitude feature descriptor-a rotation, scale, and
      illumination invariant descriptor that achieves comparable performance to SIFT on
      a large variety of image registration problems but with much shorter feature
      vectors. The descriptor is based on the Log-Polar Transform followed by a Fourier
      Transform and selection of the magnitude spectrum components. Selecting different
      frequency components allows optimizing for image patterns specific for a
      particular application. In addition, by relying only on coordinates of the found
      features and (optionally) feature sizes our descriptor is completely detector
      independent. We propose 48- or 56-long feature vectors that potentially can be
      shortened even further depending on the application. Shorter feature vectors
      result in better memory usage and faster matching. This combined with the fact
      that the descriptor does not require a time-consuming feature orientation
      estimation (the rotation invariance is achieved solely by using the magnitude
      spectrum of the Log-Polar Transform) makes it particularly attractive to
      applications with limited hardware capacity. Evaluation is performed on the
      standard Oxford dataset and two different microscopy datasets; one with
      fluorescence and one with transmission electron microscopy images. Our method
      performs better than SURF and comparable to SIFT on the Oxford dataset, and
      better than SIFT on both microscopy datasets indicating that it is particularly
      useful in applications with microscopy images.

PMID- 29190738
TI  - Cervical HSV-2 infection causes cervical remodeling and increases risk for
      ascending infection and preterm birth.
AB  - Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of
      neonatal mortality worldwide. Cervical viral infections have been established as
      risk factors for PTB in women, although the mechanism leading to increased risk
      is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal
      HSV2 infection caused increased rates of preterm birth following an intra-vaginal
      bacterial infection. HSV2 infection resulted in histological changes in the
      cervix mimicking cervical ripening, including significant collagen remodeling and
      increased hyaluronic acid synthesis. Viral infection also caused aberrant
      expression of estrogen and progesterone receptor in the cervical epithelium.
      Further analysis using human ectocervical cells demonstrated a role for Src
      kinase in virus-mediated changes in estrogen receptor and hyaluronic acid
      expression. In conclusion, HSV2 affects proteins involved in tissue hormone
      responsiveness, causes significant changes reminiscent of premature cervical
      ripening, and increases risk of preterm birth. Studies such as this improve our
      chances of identifying clinical interventions in the future.

PMID- 29190739
TI  - Anthelminthic activity of glibenclamide on secondary cystic echinococcosis in
      mice.
AB  - Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by the larval
      stage of Echinococcus granulosus. Current chemotherapy against this disease is
      based on the administration of benzimidazoles (BZMs). However, BZM treatment has
      a low cure rate and causes several side effects. Therefore, new treatment options
      are needed. The antidiabetic drug glibenclamide (Glb) is a second-generation
      sulfonylurea receptor inhibitor that has been shown to be active against
      protozoan parasites. Hence, we assessed the in vitro and in vivo pharmacological
      effects of Glb against the larval stage of E. granulosus. The in vitro activity
      was concentration dependent on both protoscoleces and metacestodes. Moreover, Glb
      combined with the minimum effective concentration of albendazole sulfoxide
      (ABZSO) was demonstrated to have a greater effect on metacestodes in comparison
      with each drug alone. Likewise, there was a reduction in the cyst weight after
      oral administration of Glb to infected mice (5 mg/kg of body weight administered
      daily for a period of 8 weeks). However, in contrast to in vitro assays, no
      differences in effectiveness were found between Glb + albendazole (ABZ) combined
      treatment and Glb monotherapy. Our results also revealed mitochondrial membrane
      depolarization and an increase in intracellular Ca2+ levels in Glb-treated
      protoscoleces. In addition, the intracystic drug accumulation and our
      bioinformatic analysis using the available E. granulosus genome suggest the
      presence of genes encoding sulfonylurea transporters in the parasite. Our data
      clearly demonstrated an anti-echinococcal effect of Glb on E. granulosus larval
      stage. Further studies are needed in order to thoroughly investigate the
      mechanism involved in the therapeutic response of the parasite to this
      sulfonylurea.

PMID- 29190740
TI  - Correlation of serum cytokines, chemokines, growth factors and enzymes with
      periodontal disease parameters.
AB  - BACKGROUND: Periodontal disease (PD) is characterized by inflammatory tissue
      destruction in tooth supporting apparatus. Many studies indicate that the
      underlying pathogenesis is in concordance with rheumatoid arthritis (RA) sharing
      immune-inflammatory events affect both diseases. The aim of this study was to
      investigate serum cytokines, chemokines, growth factors, enzymes and
      costimulatory proteins in association with periodontal conditions in PD and RA
      subjects. MATERIALS & METHODS: Periodontal examination was performed in RA (n =
      38), PD (n = 38) and healthy subjects (n = 14). Bleeding on probing (BOP) and
      probing pocket depth (PPD) were measured. Marginal bone loss (MBL) for premolars
      and molars was measured on digital panoramic radiographs. PD was defined as
      present if the PPD was >=5mm in >= 3 different sites. Serum samples were
      collected from all subjects. A multiplex proximity extension assay (PEA) was used
      to analyze the samples for simultaneous measurement of 92 cytokines. Cytokines
      with >= 60% quantitative results were included. RESULTS: A significant positive
      correlation was seen for ST1A1, FGF-19 and NT-3 whereas EN-RAGE, DNER, CX3CL1 and
      TWEAK associated inversely with BOP, PPD>= 5mm and MBL but positively with number
      of teeth. Several CD markers (CD244, CD40, CDCP1, LIF-R, IL-10RA, CD5 and CD6)
      were found to be associated with BOP, shallow and deep pockets, MBL and number of
      teeth, either directly or inversely. Most chemokines (CCL8, CX3CL1, CXCL10,
      CXCL11, CCL11, CCL4, CCL20, CXCL5, CXCL6, and CCL23) were positively associated
      with number of teeth and some inversely related to MBL (CCL8, CXCL10). Proteins
      with enzymatic activity (ST1A1, HGF and CASP-8) were directly related to the
      severity of periodontal conditions and inversely related to number of teeth.
      Aside from FGF-19, other growth factors were also directly associated with MBL
      (HGF), number of teeth (VEGF-A, LAP TGF-beta-1) and, inversely to, shallow
      pockets (LAP TGF-beta-1, TGFA and Beta-NGF). Out of 33 cytokines, 32 associated
      inversely with shallow pockets, whereas only CD40 associated positively.
      Associations between cytokines and periodontal parameters in the RA group were
      comparatively less. Statistical analyses were adjusted for multivariate effects
      using the Benjamini-Hochberg false discovery rate method. CONCLUSION: Systemic
      inflammatory burden, via known and novel markers, is associated with periodontal
      conditions in PD and RA subjects. Shallow pockets are not associated with a
      higher inflammatory state.

PMID- 29190741
TI  - Preoperative transcranial direct current stimulation: Exploration of a novel
      strategy to enhance neuroplasticity before surgery to control postoperative pain.
      A randomized sham-controlled study.
AB  - BACKGROUND: An imbalance in the excitatory/inhibitory systems in the pain
      networks may explain the persistent chronic pain after hallux valgus surgery.
      Thus, to contra-regulate this dysfunction, the use of transcranial direct current
      stimulation (tDCS) becomes attractive. OBJECTIVE: We tested the hypothesis that
      two preoperative active(a)-tDCS sessions compared with sham(s)-tDCS could improve
      the postoperative pain [as indexed by Visual Analogue Scale (VAS) at rest and
      during walking (primary outcomes)]. To assess their effect on the change in the
      Numerical Pain Scale (NPS0-10) during Conditioned Pain Modulation (CPM-task),
      disability related to pain (DRP) and analgesic consumption (secondary outcomes).
      Also, we assessed if the brain derived neurotrophic factor (BDNF) in the cerebral
      spinal fluid (CSF) after tDCS could predict the intervention's effect on the DRP.
      METHODS: It is a prospective, double blind, sham-controlled, randomized single
      center, 40 women (18-70 years-old) who had undergone hallux valgus surgery were
      randomized to receive two sessions (20 minutes each) of anodal a-tDCS or s-tDCS
      on the primary motor cortex at night and in the morning before the surgery. To
      assess the DRP was used the Brazilian Profile of Chronic Pain: Screen (B-PCP:S).
      RESULTS: A-tDCS group showed lower scores on VAS at rest and during walking
      (P<0.001). At rest, the difference between groups was 2.13cm (95%CI = 1.59 to
      2.68) while during walking was 1.67cm (95%CI = 1.05 to 2.28). A-tDCS, when
      compared to s-tDCS reduced analgesic doses in 73.25% (P<0.001), produced a
      greater reduction in B-PCP:S (mean difference of 9.41 points, 95%CI = 0.63 to
      18.21) and higher function of descending pain modulatory system (DPMS) during CPM
      task. CONCLUSION: A-tDCS improves postoperative pain, the DRP and the function of
      DPMS. Also, the CSF BDNF after a-tDCS predicted the improvement in the DRP. In
      overall, these findings suggest that a-tDCS effects may be mediated by top-down
      regulatory mechanisms associated with the inhibitory cortical control. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02360462.

PMID- 29190742
TI  - Effect of nursing care hours on the outcomes of Intensive Care assistance.
AB  - OBJECTIVES: To correlate the average number of nursing care hours dedicated to
      Intensive Care Unit (ICU) patients with nursing care indicators. METHOD:
      Transverse, descriptive study conducted between 2011 and 2013. Data were obtained
      from the electronic records system and from the nursing staff daily schedule.
      Generalized Linear Models were used for analysis. RESULTS: A total of 1,717
      patients were included in the study. The average NAS (Nursing Activities Score)
      value was 54.87. The average ratio between the number of nursing care hours
      provided to the patient and the number of nursing care hours required by the
      patient (hours ratio) was 0.87. Analysis of the correlation between nursing care
      indicators and the hours ratio showed that the indicators phlebitis and
      ventilator-associated pneumonia significantly correlated with hours ratio; that
      is, the higher the hours ratio, the lower the incidence of phlebitis and
      ventilator-associated pneumonia. CONCLUSION: The number of nursing care hours
      directly impacts patient outcomes, which makes adjustment of nurse staffing
      levels essential.

PMID- 29190743
TI  - Crystal structure of a tripartite complex between C3dg, C-terminal domains of
      factor H and OspE of Borrelia burgdorferi.
AB  - Complement is an important part of innate immunity. The alternative pathway of
      complement is activated when the main opsonin, C3b coats non-protected surfaces
      leading to opsonisation, phagocytosis and cell lysis. The alternative pathway is
      tightly controlled to prevent autoactivation towards host cells. The main
      regulator of the alternative pathway is factor H (FH), a soluble glycoprotein
      that terminates complement activation in multiple ways. FH recognizes host cell
      surfaces via domains 19-20 (FH19-20). All microbes including Borrelia
      burgdorferi, the causative agent of Lyme borreliosis, must evade complement
      activation to allow the infectious agent to survive in its host. One major
      mechanism that Borrelia uses is to recruit FH from host. Several outer surface
      proteins (Osp) have been described to bind FH via the C-terminus, and OspE is one
      of them. Here we report the structure of the tripartite complex formed by OspE,
      FH19-20 and C3dg at 3.18 A, showing that OspE and C3dg can bind simultaneously to
      FH19-20. This verifies that FH19-20 interacts via the "common microbial binding
      site" on domain 20 with OspE and simultaneously and independently via domain 19
      with C3dg. The spatial organization of the tripartite complex explains how OspE
      on the bacterial surface binds FH19-20, leaving FH fully available to protect the
      bacteria against complement. Additionally, formation of tripartite complex
      between FH, microbial protein and C3dg might enable enhanced protection,
      particularly on those regions on the bacteria where previous complement
      activation led to deposition of C3d. This might be especially important for slow
      growing bacteria that cause chronic disease like Borrelia burgdorferi.

PMID- 29190744
TI  - Prevalence and association of metabolic syndrome and vitamin D deficiency among
      postmenopausal women in a rural block of West Bengal, India.
AB  - BACKGROUND: Prevalence of metabolic syndrome (MS) and vitamin D deficiency was
      reported among postmenopausal women (PMW) in India. However, no report is
      available regarding the association of MS and 25-hydroxyvitamin D [25(OH)D] among
      PMW in India. This study aimed to find out the prevalence of MS and 25(OH)D
      status as well as their association among rural PMW of West Bengal, India.
      MATERIALS AND METHODS: This cross-sectional study was conducted among 222
      randomly selected rural PMW in Singur Block, West Bengal, India. Serum 25(OH)D,
      Blood pressure (BP), waist circumference (WC), fasting blood glucose (FBG),
      triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) were measured
      using standard procedures. MS was defined as per International Diabetes
      Federation, 2005 (for Asian-Indians) criteria. Statistical tests were done using
      SPSS software. RESULTS: Prevalence of metabolic syndrome was 46%. 51% and 19% PMW
      were vitamin D insufficient and deficient, respectively. 22% and 53% women having
      MS were vitamin D insufficient and deficient, respectively. Among the PMW, 21%
      and 47% with WC>=80cm; 22% and 62% with FBG>=110mg/dl; 21% and 54% with
      TG>=150mg/dl; 23% and 51% with HDL-C<50mg/dl, 15% and 55% with BP>=130/85mm of Hg
      were vitamin D insufficient and deficient, respectively. Significant statistical
      association between FBG and 25(OH)D status existed (p = 0.01). Significant
      positive correlation between WC and 25(OH)D level (p = 0.004) and significant
      negative correlation between FBG and 25(OH)D level observed (p = 0.02). WC was
      the only statistically significant predictor of the dependent variable. Odds of
      non-sufficient 25(OH)D level increased with decrease in WC. CONCLUSION: High
      prevalence of MS as well as vitamin D insufficiency and deficiency existed among
      PMW of Singur block, West Bengal, India. 25(OH)D had significant inverse and
      direct relationship with FBG and WC. Low 25(OH)D may be one of the potential risk
      factors for developing MS in PMW or vice-versa.

PMID- 29190745
TI  - Colonization with Escherichia coli EC 25 protects neonatal rats from necrotizing
      enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality
      in premature infants; yet its pathogenesis remains poorly understood. To evaluate
      the role of intestinal bacteria in protection against NEC, we assessed the
      ability of naturally occurring intestinal colonizer E. coli EC25 to influence
      composition of intestinal microbiota and NEC pathology in the neonatal rat model.
      Experimental NEC was induced in neonatal rats by formula feeding/hypoxia, and
      graded histologically. Bacterial populations were characterized by plating on
      blood agar, scoring colony classes, and identifying each class by sequencing 16S
      rDNA. Binding of bacteria to, and induction of apoptosis in IEC-6 enterocytes
      were examined by plating on blood agar and fluorescent staining for fragmented
      DNA. E. coli EC 25, which was originally isolated from healthy rats, efficiently
      colonized the intestine and protected from NEC following introduction to newborn
      rats with formula at 106 or 108 cfu. Protection did not depend significantly on
      EC25 inoculum size or load in the intestine, but positively correlated with the
      fraction of EC25 in the microbiome. Introduction of EC25 did not prevent
      colonization with other bacteria and did not significantly alter bacterial
      diversity. EC25 neither induced cultured enterocyte apoptosis, nor protected from
      apoptosis induced by an enteropathogenic strain of Cronobacter muytjensii. Our
      results show that E. coli EC25 is a commensal strain that efficiently colonizes
      the neonatal intestine and protects from NEC.

PMID- 29190747
TI  - Characterizing the heterogeneity of tumor tissues from spatially resolved
      molecular measures.
AB  - BACKGROUND: Tumor heterogeneity can manifest itself by sub-populations of cells
      having distinct phenotypic profiles expressed as diverse molecular, morphological
      and spatial distributions. This inherent heterogeneity poses challenges in terms
      of diagnosis, prognosis and efficient treatment. Consequently, tools and
      techniques are being developed to properly characterize and quantify tumor
      heterogeneity. Multiplexed immunofluorescence (MxIF) is one such technology that
      offers molecular insight into both inter-individual and intratumor heterogeneity.
      It enables the quantification of both the concentration and spatial distribution
      of 60+ proteins across a tissue section. Upon bioimage processing, protein
      expression data can be generated for each cell from a tissue field of view.
      RESULTS: The Multi-Omics Heterogeneity Analysis (MOHA) tool was developed to
      compute tissue heterogeneity metrics from MxIF spatially resolved tissue imaging
      data. This technique computes the molecular state of each cell in a sample based
      on a pathway or gene set. Spatial states are then computed based on the spatial
      arrangements of the cells as distinguished by their respective molecular states.
      MOHA computes tissue heterogeneity metrics from the distributions of these
      molecular and spatially defined states. A colorectal cancer cohort of
      approximately 700 subjects with MxIF data is presented to demonstrate the MOHA
      methodology. Within this dataset, statistically significant correlations were
      found between the intratumor AKT pathway state diversity and cancer stage and
      histological tumor grade. Furthermore, intratumor spatial diversity metrics were
      found to correlate with cancer recurrence. CONCLUSIONS: MOHA provides a simple
      and robust approach to characterize molecular and spatial heterogeneity of
      tissues. Research projects that generate spatially resolved tissue imaging data
      can take full advantage of this useful technique. The MOHA algorithm is
      implemented as a freely available R script (see supplementary information).

PMID- 29190746
TI  - Hepatic Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) regulates
      metabolism in mice.
AB  - BACKGROUND & AIMS: Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) and its
      partners hypoxia-inducible factors (HIF)-1alpha and HIF-2alpha are candidate
      factors for the well-known link between the liver, metabolic dysfunction and
      elevation in circulating lipids and glucose. Methods: Hepatocyte-specific ARNT
      null (LARNT), HIF-1alpha-null (LHIF1alpha) and HIF-2alpha-null (LHIF2alpha) mice
      were created. RESULTS: LARNT mice had increased fasting glucose, impaired glucose
      tolerance, increased glucose production, raised post-prandial serum triglycerides
      (TG) and markedly lower hepatic ATP versus littermate controls. There was
      increased expression of G6Pase, Chrebp, Fas and Scd-1 mRNAs in LARNT animals.
      Surprisingly, LHIF1alpha and LHIF2alpha mice exhibited no alterations in any
      metabolic parameter assessed. CONCLUSIONS: These results provide convincing
      evidence that reduced hepatic ARNT can contribute to inappropriate hepatic
      glucose production and post-prandial dyslipidaemia. Hepatic ARNT may be a novel
      therapeutic target for improving post-prandial hypertriglyceridemia and glucose
      homeostasis.

PMID- 29190748
TI  - Low hepatitis C antibody screening rates among an insured population of
      Tennessean Baby Boomers.
AB  - INTRODUCTION: Chronic Hepatitis C Virus (HCV) infection is common and can cause
      liver disease and death. Persons born from 1945 through 1965 ("Baby Boomers")
      have relatively high prevalence of chronic HCV infection, prompting
      recommendations that all Baby Boomers be screened for HCV. If chronic HCV is
      confirmed, evaluation for antiviral treatment should be performed. Direct-acting
      antivirals can cure more than 90% of people with chronic HCV. This sequence of
      services can be referred to as the HCV "cascade of cure" (CoC). The Tennessee
      (TN) Department of Health (TDH) and a health insurer with presence in TN aimed to
      determine the proportion of Baby Boomers who access HCV screening services and
      appropriately navigate the HCV CoC in TN. METHODS: TDH surveillance data and
      insurance claim records were queried to identify the cohort of Baby Boomers
      eligible for HCV testing. Billing codes and pharmacy records from 2013 through
      2015 were used to determine whether HCV screening and other HCV-related services
      were provided. The proportion of individuals accessing HCV screening and other
      steps along the HCV CoC was determined. Multivariable analyses were performed to
      identify factors associated with HCV screening and treatment. RESULTS: Among
      501,388 insured Tennessean Baby Boomers, 7% were screened for HCV. Of the 40,019
      who received any HCV-related service, 86% were screened with an HCV antibody
      test, 20% had a confirmatory HCV PCR, 9% were evaluated for treatment, and 4%
      were prescribed antivirals. Hispanics were more likely to be screened and treated
      for HCV than non-Hispanic whites. HCV screening was more likely to occur in the
      Nashville-Davidson region than in other regions of TN, but there were regional
      variations in HCV treatment. CONCLUSIONS: Many insured Tennessean Baby Boomers do
      not access HCV screening services, despite national recommendations. Demographic
      and regional differences in uptake along the HCV CoC should inform public health
      interventions aimed at mitigating the effects of chronic HCV.

PMID- 29190749
TI  - Physiological and fitness differences between cytotypes vary with stress in a
      grassland perennial herb.
AB  - BACKGROUND AND AIMS: Understanding the consequences of polyploidization is a
      major step towards assessing the importance of this mode of speciation. Most
      previous studies comparing different cytotypes, however, did so only within a
      single environment and considered only one group of traits. To take a step
      further, we need to explore multiple environments and a wide range of traits. The
      aim of this study was to assess response of diploid and autotetraploid
      individuals of Knautia arvensis (Dipsacaceae) to two stress conditions, shade or
      drought. METHODS: We studied eleven photosynthetic, morphological and fitness
      parameters of the plants over three years in a common garden under ambient
      conditions and two types of stress. KEY RESULTS: The results indicate strong
      differences in performance and physiology between cytotypes in ambient
      conditions. Interestingly, higher fitness in diploids contrasted with more
      efficient photosynthesis in tetraploids in ambient conditions. However, stress,
      especially drought, strongly reduced fitness and disrupted function of the
      photosystems in both cytotypes reducing the between cytotype differences. The
      results indicate that drought stress reduced function of the photosynthetic
      processes in both cytotypes but particularly in tetraploids, while fitness
      reduction was stronger in diploids. CONCLUSIONS: The photosynthesis related
      traits show higher plasticity in polyploids as theoretically expected, while the
      fitness related traits show higher plasticity in diploids especially in response
      to drought. This suggests that between cytotype comparisons need to consider
      multiple traits and multiple environments to understand the breath of possible
      responses of different cytotypes to stress. They also show that integrating
      results based on different traits is not straightforward and call for better
      mechanistic understanding of the relationships between species photosynthetic
      activity and fitness. Still, considering multiple environments and multiple
      species traits is crucial for understanding the drivers of niche differentiation
      between cytotypes in future studies.

PMID- 29190750
TI  - The joint effect of personality traits and perceived stress on pedestrian
      behavior in a Chinese sample.
AB  - While improper pedestrian behavior has become an important factor related to road
      traffic fatalities, especially in developing countries, the effects of
      personality traits and/or stress on pedestrian behavior have been rarely
      reported. The current study explored the joint effects of five personality traits
      (i.e., extraversion, openness, neuroticism, normlessness and altruism) and global
      perceived stress (measured with the Perceived Stress Scale-10) on pedestrian
      behavior (measured with the Pedestrian Behavior Scale) in 311 Chinese
      individuals. Results showed that altruism, neuroticism and openness significantly
      affected different pedestrian behavior dimensions, while global perceived stress
      also significantly and positively predicted positive behavior. Moreover, the
      effect of neuroticism on positive behavior was fully mediated by stress. Some
      explanations and implications are provided in the discussion section.

PMID- 29190751
TI  - Acute effect of dietary nitrate on forearm muscle oxygenation, blood volume and
      strength in older adults: A randomized clinical trial.
AB  - Both recovery time of post-exercise muscle oxygenation and muscle strength
      decline with aging. Although beetroot consumption has been shown to improve
      muscle oxygenation and exercise performance in adults, these effects in the
      elderly has not been addressed. The aim of the present study was to evaluate the
      effect of a beetroot-based gel (BG) on muscle O2 saturation, blood volume (tHb)
      and handgrip strength in the elderly in response to handgrip exercise. In a
      randomized crossover double-blind design, twelve older subjects consumed BG (100
      g of beetroot-based gel containing ~ 12 mmol nitrate) or PLA (100 g of nitrate
      depleted gel nitrate-depleted). The subjects performed a rhythmic handgrip
      exercise which consisted of a one 1-min set at 30% of the maximal voluntary
      contraction (MVC) of each subject, followed by a 1 min recovery. The muscle
      oxygenation parameters and tHb were continuously monitored by using near-infrared
      spectroscopy. MVC was evaluated at baseline, immediately after exercise, and 30
      min afterwards. The muscle O2 resaturation rate during exercise recovery was
      greater in the BG when compared to PLA condition (1.43 +/- 0.77 vs 1.02 +/-
      0.48%.s-1; P < 0.05). Significant increase was observed in tHb during exercise
      recovery (10.25 +/- 5.47 vs 6.72 +/- 4.55 MUM; P < 0.05) and significant
      reduction of handgrip strength decline was observed 30 min after exercise in BG (
      0.24 +/- 0.18 vs-0.39 +/- 0.20 N; P < 0.05). In summary, a single dose of a
      beetroot-based gel speeds up muscle O2 resaturation, increases blood volume and
      improves recovery of handgrip strength after handgrip exercise in older adults.

PMID- 29190753
TI  - Children and young people's perceptions of energy drinks: A qualitative study.
AB  - BACKGROUND: Consumption of soft drinks is declining in many countries, yet energy
      drink sales continue to increase, particularly amongst young consumers. Little is
      currently known about the drivers behind these trends. Energy drinks are high in
      sugar and caffeine, and evidence indicates that regular or heavy use by under 18s
      is likely to be detrimental to health. This study aimed to explore children and
      young people's attitudes and perceptions in relation to energy drinks in a UK
      context. METHODS: Eight focus groups were conducted with pupils aged 10-11 years
      (n = 20) and 13-14 years (n = 17) from four schools in northern England. A sub
      sample also took part in a mapping exercise to generate further insights. Data
      were analysed using the constant comparative approach. RESULTS: Energy drinks
      were reportedly consumed in a variety of public and private places, generally
      linked to social activities, sports and computer gaming (particularly amongst
      boys). Participants demonstrated strong brand awareness and preferences that were
      linked to taste and perceived value for money. The relatively low price of energy
      drinks and their widespread availability were identified as key factors, along
      with gendered branding and marketing. Some participants demonstrated a critical
      approach to manufacturers' claims and many were keen to become better informed,
      often through school- or peer-based interventions. Other potential interventions
      included age restrictions, voluntary schemes involving retailers and improved
      labelling. CONCLUSIONS: The lack of a single dominant factor in participants'
      consumption choices suggests that there is unlikely to be a 'silver bullet' in
      attempting to address this issue. However, the findings provide support for
      policy-level interventions that seek to change the behaviours of manufacturers
      and retailers as well as consumers, and actively involve children and young
      people where possible.

PMID- 29190752
TI  - Differential transcriptome profiling of chilling stress response between shoots
      and rhizomes of Oryza longistaminata using RNA sequencing.
AB  - Rice (Oryza sativa) is very sensitive to chilling stress at seedling and
      reproductive stages, whereas wild rice, O. longistaminata, tolerates non-freezing
      cold temperatures and has overwintering ability. Elucidating the molecular
      mechanisms of chilling tolerance (CT) in O. longistaminata should thus provide a
      basis for rice CT improvement through molecular breeding. In this study, high
      throughput RNA sequencing was performed to profile global transcriptome
      alterations and crucial genes involved in response to long-term low temperature
      in O. longistaminata shoots and rhizomes subjected to 7 days of chilling stress.
      A total of 605 and 403 genes were respectively identified as up- and down
      regulated in O. longistaminata under 7 days of chilling stress, with 354 and 371
      differentially expressed genes (DEGs) found exclusively in shoots and rhizomes,
      respectively. GO enrichment and KEGG pathway analyses revealed that multiple
      transcriptional regulatory pathways were enriched in commonly induced genes in
      both tissues; in contrast, only the photosynthesis pathway was prevalent in genes
      uniquely induced in shoots, whereas several key metabolic pathways and the
      programmed cell death process were enriched in genes induced only in rhizomes.
      Further analysis of these tissue-specific DEGs showed that the CBF/DREB1 regulon
      and other transcription factors (TFs), including AP2/EREBPs, MYBs, and WRKYs,
      were synergistically involved in transcriptional regulation of chilling stress
      response in shoots. Different sets of TFs, such as OsERF922, OsNAC9, OsWRKY25,
      and WRKY74, and eight genes encoding antioxidant enzymes were exclusively
      activated in rhizomes under long-term low-temperature treatment. Furthermore,
      several cis-regulatory elements, including the ICE1-binding site, the GATA
      element for phytochrome regulation, and the W-box for WRKY binding, were highly
      abundant in both tissues, confirming the involvement of multiple regulatory genes
      and complex networks in the transcriptional regulation of CT in O.
      longistaminata. Finally, most chilling-induced genes with alternative splicing
      exclusive to shoots were associated with photosynthesis and regulation of gene
      expression, while those enriched in rhizomes were primarily related to stress
      signal transduction; this indicates that tissue-specific transcriptional and post
      transcriptional regulation mechanisms synergistically contribute to O.
      longistaminata long-term CT. Our findings provide an overview of the complex
      regulatory networks of CT in O. longistaminata.

PMID- 29190754
TI  - Encryption of agonistic motifs for TLR4 into artificial antigens augmented the
      maturation of antigen-presenting cells.
AB  - Adjuvants are indispensable for achieving a sufficient immune response from
      vaccinations. From a functional viewpoint, adjuvants are classified into two
      categories: "physical adjuvants" increase the efficacy of antigen presentation by
      antigen-presenting cells (APC) and "signal adjuvants" induce the maturation of
      APC. Our previous study has demonstrated that a physical adjuvant can be
      encrypted into proteinous antigens by creating artificial proteins from
      combinatorial assemblages of epitope peptides and those peptide sequences having
      propensities to form certain protein structures (motif programming). However, the
      artificial antigens still require a signal adjuvant to maturate the APC; for
      example, co-administration of the Toll-like receptor 4 (TLR4) agonist
      monophosphoryl lipid A (MPLA) was required to induce an in vivo immunoreaction.
      In this study, we further modified the previous artificial antigens by appending
      the peptide motifs, which have been reported to have agonistic activity for TLR4,
      to create "adjuvant-free" antigens. The created antigens with triple TLR4
      agonistic motifs in their C-terminus have activated NF-kappaB signaling pathways
      through TLR4. These proteins also induced the production of the inflammatory
      cytokine TNF-alpha, and the expression of the co-stimulatory molecule CD40 in
      APC, supporting the maturation of APC in vitro. Unexpectedly, these signal
      adjuvant-encrypted proteins have lost their ability to be physical adjuvants
      because they did not induce cytotoxic T lymphocytes (CTL) in vivo, while the
      parental proteins induced CTL. These results confirmed that the manifestation of
      a motif's function is context-dependent and simple addition does not always work
      for motif-programing. Further optimization of the molecular context of the TLR4
      agonistic motifs in antigens should be required to create adjuvant-free antigens.

PMID- 29190755
TI  - Towards improving sterile insect technique: Exposure to orange oil compounds
      increases sexual signalling and longevity in Ceratitis capitata males of the
      Vienna 8 GSS.
AB  - The Mediterranean fruit fly (medfly), Ceratitis capitata, is a notorious insect
      pest causing huge economic losses worldwide. The sterile insect technique (SIT)
      is widely used for its control. Using sexually mature sterilized males of the
      Vienna 8 (tsl) strain in the laboratory, we explored whether exposure of males to
      citrus compounds (separately or in a mixture) affects their sexual behaviour and
      if nutritional conditions and age modulate those effects. Exposed males exhibited
      increased sexual signalling compared to unexposed ones, particularly when fed a
      rich adult diet. Interestingly, and for the first time reported in medfly,
      exposure of Vienna 8 males to a mixture of citrus compounds increases longevity
      under poor adult diet conditions. We discuss the possible associated mechanisms
      and provide some practical implications of our results towards improving the
      effectiveness of SIT.

PMID- 29190756
TI  - Visualizing the spatiotemporal map of Rac activation in bovine aortic endothelial
      cells under laminar and disturbed flows.
AB  - Disturbed flow can eliminate the alignment of endothelial cells in the direction
      of laminar flow, and significantly impacts on atherosclerosis in collateral
      arteries near the bifurcation and high curvature regions. While shear stress
      induced Rac polarity has been shown to play crucial roles in cell polarity and
      migration, little is known about the spatiotemporal map of Rac under disturbed
      flow, and the mechanism of flow-induced cell polarity still needs to be
      elucidated. In this paper, disturbed flow or laminar flow with 15 dyn/cm2 of
      average shear stress was applied on bovine aortic endothelial cells (BAECs) for
      30 minutes. A genetically-encoded PAK-PBD-GFP reporter was transfected into BAECs
      to visualize the real-time activation of Rac in living cell under fluorescence
      microscope. The imaging of the fluorescence intensity was analyzed by Matlab and
      the normalized data was converted into 3D spatiotemporal map. Then the changes of
      data upon chemical interference were fitted with logistic curve to explore the
      rule and mechanism of Rac polarity under laminar or disturbed flow. A polarized
      Rac activation was observed at the downstream edge along the laminar flow, which
      was enhanced by benzol alcohol-enhanced membrane fluidity but inhibited by
      nocodazole-disrupted microtubules or cholesterol-inhibited membrane fluidity,
      while no obvious polarized Rac activation could be found upon disturbed flow
      application. It is concluded that disturbed flow inhibits the flow-induced Rac
      polarized activation, which is related to the interaction of cell membrane and
      cytoskeleton, especially the microtubules.

PMID- 29190758
TI  - The influence of anticipated pride and guilt on pro-environmental decision
      making.
AB  - The present research explores the relationship between anticipated emotions and
      pro-environmental decision making comparing two differently valenced emotions:
      anticipated pride and guilt. In an experimental design, we examined the causal
      effects of anticipated pride versus guilt on pro-environmental decision making
      and behavioral intentions by making anticipated emotions (i.e. pride and guilt)
      salient just prior to asking participants to make a series of environmental
      decisions. We find evidence that anticipating one's positive future emotional
      state from green action just prior to making an environmental decision leads to
      higher pro-environmental behavioral intentions compared to anticipating one's
      negative emotional state from inaction. This finding suggests a rethinking in the
      domain of environmental and climate change messaging, which has traditionally
      favored inducing negative emotions such as guilt to promote pro-environmental
      action. Furthermore, exploratory results comparing anticipated pride and guilt
      inductions to baseline behavior point toward a reactance eliciting effect of
      anticipated guilt.

PMID- 29190757
TI  - Long-lived weight-reduced alphaMUPA mice show higher and longer maternal
      dependent postnatal leptin surge.
AB  - We investigated whether long-lived weight-reduced alphaMUPA mice differ from
      their wild types in postnatal body composition and leptin level, and whether
      these differences are affected by maternal-borne factors. Newborn alphaMUPA and
      wild type mice had similar body weight and composition up to the third postnatal
      week, after which alphaMUPA mice maintained lower body weight due to lower fat
      free mass. Both strains showed a surge in leptin levels at the second postnatal
      week, initiating earlier in alphaMUPA mice, rising higher and lasting longer than
      in the wild types, mainly in females. Leptin level in dams' serum and breast
      milk, and in their pup's stomach content were also higher in alphaMUPA than in
      the WT during the surge peak. Leptin surge preceded the strain divergence in body
      weight, and was associated with an age-dependent decrease in the leptin:fat mass
      ratio-suggesting that postnatal sex and strain differences in leptin ontogeny are
      strongly influenced by processes independent of fat mass, such as production and
      secretion, and possibly outside fat tissues. Dam removal elevated corticosterone
      level in female pups from both strains similarly, yet mitigated the leptin surge
      only in alphaMUPA-eliminating the strain differences in leptin levels. Overall,
      our results indicate that alphaMUPA's postnatal leptin surge is more pronounced
      than in the wild type, more sensitive to maternal deprivation, less related to
      pup's total adiposity, and is associated with a lower post-weaning fat-free mass.
      These strain-related postnatal differences may be related to alphaMUPA's higher
      milk-borne leptin levels. Thus, our results support the use of alphaMUPA mice in
      future studies aimed to explore the relationship between maternal (i.e. milk
      borne) factors, postnatal leptin levels, and post-weaning body composition and
      energy homeostasis.

PMID- 29190759
TI  - Graph-based analysis of brain connectivity in schizophrenia.
AB  - The present study evaluated brain connectivity using electroencephalography (EEG)
      data from 14 patients with schizophrenia and 14 healthy controls. Phase-Locking
      Value (PLV), Phase-Lag Index (PLI) and Directed Transfer Function (DTF) were
      calculated for the original EEG data and following current source density (CSD)
      transformation, re-referencing using the average reference electrode (AVERAGE)
      and reference electrode standardization techniques (REST). The statistical
      analysis of adjacency matrices was carried out using indices based on graph
      theory. Both CSD and REST reduced the influence of volume conducted currents. The
      largest group differences in connectivity were observed for the alpha band.
      Schizophrenic patients showed reduced connectivity strength, as well as a lower
      clustering coefficient and shorter characteristic path length for both measures
      of phase synchronization following CSD transformation or REST re-referencing.
      Reduced synchronization was accompanied by increased directional flow from the
      occipital region for the alpha band. Following the REST re-referencing, the
      sources of alpha activity were located at parietal rather than occipital
      derivations. The results of PLV and DTF demonstrated group differences in fronto
      posterior asymmetry following CSD transformation, while for PLI the differences
      were significant only using REST. The only analysis that identified group
      differences in inter-hemispheric asymmetry was DTF calculated for REST. Our
      results suggest that a comparison of different connectivity measures using graph
      based indices for each frequency band, separately, may be a useful tool in the
      study of disconnectivity disorders such as schizophrenia.

PMID- 29190760
TI  - Simulated ocean acidification reveals winners and losers in coastal
      phytoplankton.
AB  - The oceans absorb ~25% of the annual anthropogenic CO2 emissions. This causes a
      shift in the marine carbonate chemistry termed ocean acidification (OA). OA is
      expected to influence metabolic processes in phytoplankton species but it is
      unclear how the combination of individual physiological changes alters the
      structure of entire phytoplankton communities. To investigate this, we deployed
      ten pelagic mesocosms (volume ~50 m3) for 113 days at the west coast of Sweden
      and simulated OA (pCO2 = 760 MUatm) in five of them while the other five served
      as controls (380 MUatm). We found: (1) Bulk chlorophyll a concentration and 10
      out of 16 investigated phytoplankton groups were significantly and mostly
      positively affected by elevated CO2 concentrations. However, CO2 effects on
      abundance or biomass were generally subtle and present only during certain
      succession stages. (2) Some of the CO2-affected phytoplankton groups seemed to
      respond directly to altered carbonate chemistry (e.g. diatoms) while others (e.g.
      Synechococcus) were more likely to be indirectly affected through CO2 sensitive
      competitors or grazers. (3) Picoeukaryotic phytoplankton (0.2-2 MUm) showed the
      clearest and relatively strong positive CO2 responses during several succession
      stages. We attribute this not only to a CO2 fertilization of their photosynthetic
      apparatus but also to an increased nutrient competitiveness under acidified (i.e.
      low pH) conditions. The stimulating influence of high CO2/low pH on picoeukaryote
      abundance observed in this experiment is strikingly consistent with results from
      previous studies, suggesting that picoeukaryotes are among the winners in a
      future ocean.

PMID- 29190761
TI  - Acute glucoregulatory and vascular outcomes of three strategies for interrupting
      prolonged sitting time in postmenopausal women: A pilot, laboratory-based,
      randomized, controlled, 4-condition, 4-period crossover trial.
AB  - BACKGROUND: Prolonged sitting is associated with cardiometabolic and vascular
      disease. Despite emerging evidence regarding the acute health benefits of
      interrupting prolonged sitting time, the effectiveness of different modalities in
      older adults (who sit the most) is unclear. METHODS: In preparation for a future
      randomized controlled trial, we enrolled 10 sedentary, overweight or obese,
      postmenopausal women (mean age 66 years +/-9; mean body mass index 30.6 kg/m2 +/
      4.2) in a 4-condition, 4-period crossover feasibility pilot study in San Diego to
      test 3 different sitting interruption modalities designed to improve
      glucoregulatory and vascular outcomes compared to a prolonged sitting control
      condition. The interruption modalities included: a) 2 minutes standing every 20
      minutes; b) 2 minutes walking every hour; and c) 10 minutes standing every hour.
      During each 5-hr condition, participants consumed two identical, standardized
      meals. Blood samples, blood pressure, and heart rate were collected every 30
      minutes. Endothelial function of the superficial femoral artery was measured at
      baseline and end of each 5-hr condition using flow-mediated dilation (FMD).
      Participants completed each condition on separate days, in randomized order. This
      feasibility pilot study was not powered to detect statistically significant
      differences in the various outcomes, however, analytic methods (mixed models)
      were used to test statistical significance within the small sample size. RESULTS:
      Nine participants completed all 4 study visits, one participant completed 3 study
      visits and then was lost to follow up. Net incremental area under the curve
      (iAUC) values for postprandial plasma glucose and insulin during the 5-hr sitting
      interruption conditions were not significantly different compared to the control
      condition. Exploratory analyses revealed that the 2-minute standing every 20
      minutes and the 2-minute walking every hour conditions were associated with a
      significantly lower glycemic response to the second meal compared to the first
      meal (i.e., condition-matched 2-hour post-lunch glucose iAUC was lower than 2
      hour post-breakfast glucose iAUC) that withstood Bonferroni correction (p =
      0.0024 and p = 0.0084, respectively). Using allometrically scaled data, the 10
      minute standing every hour condition resulted in an improved FMD response, which
      was significantly greater than the control condition after Bonferroni correction
      (p = 0.0033). CONCLUSION: This study suggests that brief interruptions in
      prolonged sitting time have modality-specific glucoregulatory and vascular
      benefits and are feasible in an older adult population. Larger laboratory and
      real-world intervention studies of pragmatic and effective methods to change
      sitting habits are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02743286.

PMID- 29190762
TI  - Comprehensive analysis of early fractional anisotropy changes in acute ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Cerebral ischemia leads to a rapid decrease of the
      apparent diffusion coefficient. For fractional anisotropy both increase and
      decrease have been reported in acute ischemic stroke. Aim of this study was to
      characterize early water diffusion changes in a homogenous group of acute stroke
      patients and to clarify the issue of early fractional anisotropy changes and
      their relation to time from symptom onset. METHODS: MRI data of patients with
      acute ischemic stroke examined by diffusion tensor imaging within 8h after
      symptom were analyzed. We calculated fractional anisotropy, eigenvalues and the
      isotropic and anisotropic components of the diffusion tensor. The values were
      calculated as ratios between the ischemic lesion and a mirror region in the
      unaffected side and correlated with clinical parameters. RESULTS: We included 63
      patients: 49% female, mean age 69 +/- 14 years, median NIHSS on admission 9 (IQR
      4-14). For the whole sample, mean fractional anisotropy was increased (ratio:
      1.083 +/- 0.168), while all other diffusion parameters were decreased. Both the
      isotropic and anisotropic component of the diffusion tensor were decreased with a
      more pronounced decrease of the isotropic component (ratios: isotropic = 0.730 +/
      0.106, anisotropic = 0.788 +/- 0.127; p<0.001). There was no correlation of
      fractional anisotropy with time from symptom onset. Looking at individual
      patients, fractional anisotropy was increased in 70%. There were no differences
      in clinical characteristics between patients with increased and decreased
      fractional anisotropy. CONCLUSION: Fractional anisotropy increase in acute stroke
      results from a more pronounced decrease of the isotropic diffusion component and
      is not related to time from symptom onset. Thus, fractional anisotropy is not
      helpful as a surrogate marker of lesion age in the very first hours of stroke.

PMID- 29190763
TI  - In vitro activity of Spirulina platensis water extract against different Candida
      species isolated from vulvo-vaginal candidiasis cases.
AB  - The high incidence of vulvo-vaginal candidiasis, combined with the growing
      problems about azole resistance and toxicity of antifungal drugs, highlights the
      need for the development of new effective strategies for the treatment of this
      condition. In this context, natural compounds represent promising alternatives.
      The cyanobacterium Spirulina platensis, a blue-green alga, exhibits antimicrobial
      activities against several microorganisms. Nevertheless, only few data about the
      antifungal properties of Spirulina platensis are available and its potential
      toxic effects have not been largely investigated. The aim of this study was to
      evaluate the in vitro activity of a fully-characterized water extract of
      Spirulina platensis against 22 strains of Candida spp. Prior to considering its
      potential topical use, we both investigated whether the extract exerted target
      activities on guinea pig uterine smooth muscle, and the impact of Spirulina
      platensis on the dominant microorganisms of the vaginal microbiota (i.e.,
      lactobacilli), in order to exclude possible adverse events. By means of a broth
      microdilution assay, we found that the microalga extract possesses good
      antifungal properties (MIC: 0.125-0.5 mg/ml), against all the Candida species
      with a fungicidal activity. At the concentrations active against candida,
      Spirulina platensis did not modify the spontaneous basic waves pattern of uterine
      myometrium as underlined by the absence of aberrant contractions, and did not
      affect the main health-promoting bacteria of the vaginal ecosystem. Finally, we
      evaluated the selectivity index of our extract by testing its cytotoxicity on
      three different cell lines and it showed values ranging between 2 and 16. Further
      in vivo studies are needed, in particular to evaluate the use of control-release
      formulations in order to maintain Spirulina platensis concentrations at anti
      Candida active doses but below the toxic levels found in the present work.

PMID- 29190764
TI  - Selenium requirements based on muscle and kidney selenoprotein enzyme activity
      and transcript expression in the turkey poult (Meleagris gallopavo).
AB  - The current NRC selenium (Se) requirement for turkeys is 0.2 MUg Se/g diet. We
      previously fed turkey poults a Se-deficient diet (0.005 MUg Se/g) supplemented
      with 10 graded levels of Se (0, 0.025, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 1.0
      MUg Se/g as Na2SeO3, 5/treatment) for 4 wk, and found that the minimum dietary Se
      requirement was 0.3 MUg Se/g based on selenoprotein enzyme activity in blood,
      liver, gizzard and pancreas. Because the turkey is primarily a production animal,
      we expanded this analysis to kidney, heart, breast and thigh. Se concentrations
      in Se-deficient poults were 5.0, 9.8, 33, and 15% of levels in poults fed 0.4 MUg
      Se/g in liver, kidney, thigh and breast, respectively. Increasing Se
      supplementation resulted in hyperbolic response curves for all tissues;
      breakpoint analysis indicated minimum Se requirements of 0.34-0.36 MUg Se/g based
      on tissue Se levels in liver, kidney and thigh. Similarly, GPX1 activity in
      muscle tissues and kidney responded hyperbolically to increasing dietary Se,
      reaching well-defined plateaus with breakpoints at 0.30-0.36 MUg Se/g. Minimum Se
      requirements based on GPX4 activity were 0.30-0.32 MUg Se/g for breast and thigh.
      Selenoprotein transcript expression decreased significantly in Se deficiency for
      only 2, 3, 5, and 6 mRNA in breast, thigh, heart, and kidney, respectively, out
      of 24 known avian selenoproteins. Se response curves for regulated selenoprotein
      transcripts were hyperbolic, and reached well-defined plateaus with breakpoints
      in a narrow range of 0.08-0.19 MUg Se/g. No selenoprotein transcript was altered
      by supernutritional Se. In summary, these results clearly indicate that the NRC
      dietary Se requirement should be raised to 0.4 MUg Se/g, at least for poults, to
      meet the nutritional needs of the young turkey. The Se response curve plateaus
      further show that limits for turkey supplementation with selenite could safely be
      raised to 0.5 MUg Se/g diet.

PMID- 29190765
TI  - Systematics of the genus Zinaida Evans, 1937 (Hesperiidae: Hesperiinae: Baorini).
AB  - Traditionally, species of the genus Zinaida were assigned to the genus
      Polytremis, until molecular evidence revealed that the former is a distinct
      genus. Nine species in Polytremis sensu Evans have since been removed and
      assigned to Zinaida; however, there is still uncertainty as to the taxonomic
      status of an additional seven Polytremis species. Moreover, the interspecific
      relationships within Zinaida have remained unresolved. To further investigate the
      taxonomic statuses and interspecific relationships within Zinaida, a molecular
      phylogeny of most species of Zinaida and its allies was inferred based on regions
      of the mitochondrial COI-COII and 16S and nuclear EF-1alpha genes (3006 bp). The
      results revealed that Zinaida is monophyletic and consists of four intra-generic
      clades that correspond to morphological characteristics. Clade A (Z. suprema
      group) consists of P. kiraizana, Z. suprema, and P. gigantea, with the latter two
      as sister species. Clade B (Z. nascens group) consists of seven species, and is
      the sister group of Clade C (Z. pellucida group), which comprises sister species
      Z. pellucida and Z. zina. In Clade B, Z. caerulescens and Z. gotama, and Z. theca
      and Z. fukia are sister species, respectively. On the basis of our molecular
      evidence and morphological features, we have moved P. gigantea, P. kiraizana, P.
      jigongi, and P. micropunctata to the genus Zinaida as new combinations. We review
      morphological characteristics and discuss the distribution of each of these
      groups in the light of our phylogenetic hypothesis, and provide a comprehensive
      taxonomic checklist.

PMID- 29190766
TI  - Developmental peculiarities in placentae of ovine uniparental conceptuses.
AB  - Genomic imprinting is an epigenetic phenomenon regulating mono-allelic expression
      of genes depending on their parental origin. Defective genomic imprinting is
      involved in several placental disorders, such as intrauterine growth restriction
      and pre-eclampsia. Uniparental embryos, having maternal-only or paternal-only
      genomes (parthenogenotes [PAR] and androgenotes [AND], respectively), are useful
      models to study placentation. The aim of this work was to reveal the effect of
      parental genome (maternal and paternal) on placentation. To do this, uniparental
      (AND and PAR) and biparental (CTR) in vitro produced sheep embryos transferred to
      recipient females were collected at day 20 of pregnancy and their placentae were
      analyzed. qPCR analysis showed that imprinted genes (H19, IGF2R and DLK1) were
      expressed accordingly to their parental origin while the expression f DNA
      methyltransferases () was disregulated, especially in PAR (P < 0.05). AND
      placentae were significantly hypomethylated compared to both PAR and CTR (P =
      0.023). Chorion-allantoid of AND showed impaired development of vessels and
      reduced mRNA expression of vasculogenetic factors (ANG2 P = 0.05; VEGFR2 P<
      0.001; TIE2 P < 0.001). Morphologically, PAR placentae were characterized by
      abnormal structure of the trophoectodermal epithelium and reduced total number
      (P<0.03) of Trophoblastic Binucleate Cells. A reduced implantation rate of both
      classes of uniparental embryos (P<0.03) was also noted. Our results provide new
      insights into the characterization of uniparental embryos and demonstrate the
      complementary role of parental genomes for the correct establishment of
      pregnancy. Thus, our findings may suggest new targets to improve our
      understanding of the origin of imprinting-related placental dysfunction.

PMID- 29190768
TI  - Medical costs, Cesarean delivery rates, and length of stay in specialty hospitals
      vs. non-specialty hospitals in South Korea.
AB  - BACKGROUND: Since 2011, specialty hospitals in South Korea have been known for
      providing high- quality care in specific clinical areas. Much research related to
      specialty hospitals and their performance in many such areas has been performed,
      but investigations about their performance in obstetrics and gynecology are
      lacking. Thus, we aimed to compare specialty vs. non-specialty hospitals with
      respect to mode of obstetric delivery, especially the costs and length of stay
      related to Cesarean section (CS) procedures, and to provide evidence to policy
      makers for evaluating the success of hospitals that specialize in obstetric and
      gynecological (OBGYN) care. METHODS: We obtained National Health Insurance claim
      data from 2012 to 2014, which included information from 418,141 OBGYN cases at
      214 hospitals. We used a generalized estimating equation model to identify a
      potential association between the likelihood of CS at specialty hospitals
      compared with other hospitals. We also evaluated medical costs and length of stay
      in specialty hospitals according to type of delivery. RESULTS: We found that
      150,256 (35.9%) total deliveries were performed by CS. The odds ratio of CS was
      significantly lower in specialty hospitals (OR: 0.95, 95% CI: 0.93-0.96compared
      to other hospitals Medical costs (0.74%) and length of stay (1%) in CS cases
      increased in specialty hospitals, although length of stay following vaginal
      delivery was lower (0.57%) in specialty hospitals compared with other hospitals.
      CONCLUSIONS: We determined that specialty hospitals are significantly associated
      with a lower likelihood of CS delivery and shorter length of stay after vaginal
      delivery. Although they are also associated with higher costs for delivery, the
      increased cost could be due to the high level of intensive care provided, which
      leads to improve quality of care. Policy-makers should consider incentive
      programs to maintain performance of specialty hospitals and promote efficiency
      that could reduce medical costs accrued by patients.

PMID- 29190767
TI  - High DNA stability in white blood cells and buffy coat lysates stored at ambient
      temperature under anoxic and anhydrous atmosphere.
AB  - Conventional storage of blood-derived fractions relies on cold. However, lately,
      ambient temperature preservation has been evaluated by several independent
      institutions that see economic and logistic advantages in getting rid of the cold
      chain. Here we validated a novel procedure for ambient temperature preservation
      of DNA in white blood cell and buffy coat lysates based on the confinement of the
      desiccated biospecimens under anoxic and anhydrous atmosphere in original
      hermetic minicapsules. For this validation we stored encapsulated samples either
      at ambient temperature or at several elevated temperatures to accelerate aging.
      We found that DNA extracted from stored samples was of good quality with a yield
      of extraction as expected. Degradation rates were estimated from the average
      fragment size of denatured DNA run on agarose gels and from qPCR reactions. At
      ambient temperature, these rates were too low to be measured but the degradation
      rate dependence on temperature followed Arrhenius' law, making it possible to
      extrapolate degradation rates at 25 degrees C. According to these values, the DNA
      stored in the encapsulated blood products would remain larger than 20 kb after
      one century at ambient temperature. At last, qPCR experiments demonstrated the
      compatibility of extracted DNA with routine DNA downstream analyses. Altogether,
      these results showed that this novel storage method provides an adequate
      environment for ambient temperature long term storage of high molecular weight
      DNA in dehydrated lysates of white blood cells and buffy coats.

PMID- 29190769
TI  - Measuring couple relationship quality in a rural African population: Validation
      of a Couple Functionality Assessment Tool in Malawi.
AB  - Available data suggest that individual and family well-being are linked to the
      quality of women's and men's couple relationships, but few tools exist to assess
      couple relationship functioning in low- and middle-income countries. In response
      to this gap, Catholic Relief Services has developed a Couple Functionality
      Assessment Tool (CFAT) to capture valid and reliable data on various domains of
      relationship quality. This tool is designed to be used by interventions which aim
      to improve couple and family well-being as a means of measuring the effectiveness
      of these interventions, particularly related to couple relationship quality. We
      carried out a validation study of the CFAT among 401 married and cohabiting
      adults (203 women and 198 men) in rural Chikhwawa District, Malawi. Using
      psychometric scales, the CFAT addressed six domains of couple relationship
      quality (intimacy, partner support, sexual satisfaction, gender roles, decision
      making, and communication and conflict management), and included questions on
      intimate partner violence. We used exploratory factor analysis to assess scale
      performance of each domain and produce a shortened Relationship Quality Index
      (RQI) composed of items from five relationship quality domains. This article
      reports the performance of the RQI. Internal reliability and validity of the RQI
      were found to be good. Regression analyses examined the relationship of the RQI
      to outcomes important to health and development: intra-household cooperation,
      positive health behaviors, intimate partner violence, and gender-equitable norms.
      We found many significant correlations between RQI scores and these couple- and
      family-level development issues. There is a need to further validate the tool
      with use in other populations as well as to continue to explore whether the
      observed linkages between couple functionality and development outcomes are
      causal relationships.

PMID- 29190770
TI  - Genetic diversity and population structure analysis of spinach by single
      nucleotide polymorphisms identified through genotyping-by-sequencing.
AB  - Spinach (Spinacia oleracea L., 2n = 2x = 12) is an economically important
      vegetable crop worldwide and one of the healthiest vegetables due to its high
      concentrations of nutrients and minerals. The objective of this research was to
      conduct genetic diversity and population structure analysis of a collection of
      world-wide spinach genotypes using single nucleotide polymorphisms (SNPs)
      markers. Genotyping by sequencing (GBS) was used to discover SNPs in spinach
      genotypes. Three sets of spinach genotypes were used: 1) 268 USDA GRIN spinach
      germplasm accessions originally collected from 30 countries; 2) 45 commercial
      spinach F1 hybrids from three countries; and 3) 30 US Arkansas spinach
      cultivars/breeding lines. The results from this study indicated that there was
      genetic diversity among the 343 spinach genotypes tested. Furthermore, the
      genetic background in improved commercial F1 hybrids and in Arkansas
      cultivars/lines had a different structured populations from the USDA germplasm.
      In addition, the genetic diversity and population structures were associated with
      geographic origin and germplasm from the US Arkansas breeding program had a
      unique genetic background. These data could provide genetic diversity information
      and the molecular markers for selecting parents in spinach breeding programs.

PMID- 29190772
TI  - Fairness in optimizing bus-crew scheduling process.
AB  - This work proposes a model considering fairness in the problem of crew scheduling
      for bus drivers (CSP-BD) using a hybrid ant-colony optimization (HACO) algorithm
      to solve it. The main contributions of this work are the following: (a) a valid
      approach for cases with a special cost structure and constraints considering the
      fairness of working time and idle time; (b) an improved algorithm incorporating
      Gamma heuristic function and selecting rules. The relationships of each cost are
      examined with ten bus lines collected from the Beijing Public Transport Holdings
      (Group) Co., Ltd., one of the largest bus transit companies in the world. It
      shows that unfair cost is indirectly related to common cost, fixed cost and extra
      cost and also the unfair cost approaches to common and fixed cost when its
      coefficient is twice of common cost coefficient. Furthermore, the longest time
      for the tested bus line with 1108 pieces, 74 blocks is less than 30 minutes. The
      results indicate that the HACO-based algorithm can be a feasible and efficient
      optimization technique for CSP-BD, especially with large scale problems.

PMID- 29190771
TI  - Synergistic role of 5-azacytidine and ascorbic acid in directing cardiosphere
      derived cells to cardiomyocytes in vitro by downregulating Wnt signaling pathway
      via phosphorylation of beta-catenin.
AB  - BACKGROUND: Cardiosphere derived cells (CDCs) represent a valuable source in stem
      cell based therapy for cardiovascular diseases, yet poor differentiation rate
      hinders the transplantation efficiency. The aim of this study is to check the
      ability of 5-Azacytidine (Aza) alone and in combination with ascorbic acid
      (Aza+AA) in delineating CDCs to cardiomyogenesis and the underlying Wnt signaling
      mechanism in induced differentiation. METHODS: CDCs were treated with Aza and
      Aza+AA for a period of 14 days to examine the expression of cardiac specific
      markers and Wnt downstream regulators by immunofluorescence, real time PCR and
      western blot. RESULTS: Results revealed that Aza+AA induced efficient commitment
      of CDCs to cardiomyogenic lineage. Immunofluorescence analysis showed significant
      augment for Nkx 2.5, GATA 4 and alpha-Sarcomeric actinin markers in Aza+AA group
      than control group (p = 0.0118, p = 0.009 and p = 0.0091, respectively). Relative
      upregulation of cardiac markers, Nkx 2.5 (p = 0.0156), GATA 4 (p = 0.0087) and
      down regulation of Wnt markers, beta-catenin (p = 0.0107) and Cyclin D1 (p = 0.
      0116) in Aza+AA group was revealed by RNA expression analysis. Moreover, the
      Aza+AA induced prominent expression of GATA 4, alpha-Sarcomeric actinin and
      phospho beta-catenin while non phospho beta-catenin and Cyclin D1 expression was
      significantly suppressed as displayed in protein expression analysis. Generation
      of spontaneous beating in Aza+AA treated CDCs further reinforced that Aza+AA
      accelerates the cardiomyogenic potential of CDCs. CONCLUSION: Combined treatment
      of Aza along with AA implicit in inducing cardiomyogenic potential of CDCs and is
      associated with down regulating Wnt signaling pathway. Altogether, CDCs represent
      a valuable tool for the treatment of cardiovascular disorders.

PMID- 29190773
TI  - Correction: Experience with speech sounds is not necessary for cue trading by
      budgerigars (Melopsittacus undulatus).
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177676.].

PMID- 29190775
TI  - Transcriptome profiling analysis of senescent gingival fibroblasts in response to
      Fusobacterium nucleatum infection.
AB  - Periodontal disease is caused by dental plaque biofilms. Fusobacterium nucleatum
      is an important periodontal pathogen involved in the development of bacterial
      complexity in dental plaque biofilms. Human gingival fibroblasts (GFs) act as the
      first line of defense against oral microorganisms and locally orchestrate immune
      responses by triggering the production of reactive oxygen species and pro
      inflammatory cytokines (IL-6 and IL-8). The frequency and severity of periodontal
      diseases is known to increase in elderly subjects. However, despite several
      studies exploring the effects of aging in periodontal disease, the underlying
      mechanisms through which aging affects the interaction between F. nucleatum and
      human GFs remain unclear. To identify genes affected by infection, aging, or
      both, we performed an RNA-Seq analysis using GFs isolated from a single healthy
      donor that were passaged for a short period of time (P4) 'young GFs' or for
      longer period of time (P22) 'old GFs', and infected or not with F. nucleatum.
      Comparing F. nucleatum-infected and uninfected GF(P4) cells the differentially
      expressed genes (DEGs) were involved in host defense mechanisms (i.e., immune
      responses and defense responses), whereas comparing F. nucleatum-infected and
      uninfected GF(P22) cells the DEGs were involved in cell maintenance (i.e., TGF
      beta signaling, skeletal development). Most DEGs in F. nucleatum-infected GF(P22)
      cells were downregulated (85%) and were significantly associated with host
      defense responses such as inflammatory responses, when compared to the DEGs in F.
      nucleatum-infected GF(P4) cells. Five genes (GADD45b, KLF10, CSRNP1, ID1, and
      TM4SF1) were upregulated in response to F. nucleatum infection; however, this
      effect was only seen in GF(P22) cells. The genes identified here appear to
      interact with each other in a network associated with free radical scavenging,
      cell cycle, and cancer; therefore, they could be potential candidates involved in
      the aged GF's response to F. nucleatum infection. Further studies are needed to
      confirm these observations.

PMID- 29190774
TI  - Activation of the cholinergic anti-inflammatory pathway by GTS-21 attenuates
      cisplatin-induced acute kidney injury in mice.
AB  - Acute kidney injury (AKI) is the most common side effect of cisplatin, a widely
      used chemotherapy drug. Although AKI occurs in up to one third of cancer patients
      receiving cisplatin, effective renal protective strategies are lacking. Cisplatin
      targets renal proximal tubular epithelial cells leading to inflammation, reactive
      oxygen species, tubular cell injury, and eventually cell death. The cholinergic
      anti-inflammatory pathway is a vagus nerve-mediated reflex that suppresses
      inflammation via alpha7 nicotinic acetylcholine receptors (alpha7nAChRs). Our
      previous studies demonstrated the renoprotective and anti-inflammatory effects of
      cholinergic agonists, including GTS-21. Therefore, we examined the effect of GTS
      21 on cisplatin-induced AKI. Male C57BL/6 mice received either saline or GTS-21
      (4mg/kg, i.p.) twice daily for 4 days before cisplatin and treatment continued
      through euthanasia; 3 days post-cisplatin mice were euthanized and analyzed for
      markers of renal injury. GTS-21 significantly reduced cisplatin-induced renal
      dysfunction and injury (p<0.05). GTS-21 significantly attenuated renal Ptgs2/COX
      2 mRNA and IL-6, IL-1beta, and CXCL1 protein expression, as well as neutrophil
      infiltration after cisplatin. GTS-21 blunted cisplatin-induced renal ERK1/2
      activation, as well as renal ATP depletion and apoptosis (p<0.05). GTS-21
      suppressed the expression of CTR1, a cisplatin influx transporter and enhanced
      the expression of cisplatin efflux transporters MRP2, MRP4, and MRP6 (p<0.05).
      Using breast, colon, and lung cancer cell lines we showed that GTS-21 did not
      inhibit cisplatin's tumor cell killing activity. GTS-21 protects against
      cisplatin-AKI by attenuating renal inflammation, ATP depletion and apoptosis, as
      well as by decreasing renal cisplatin influx and increasing efflux, without
      impairing cisplatin-mediated tumor cell killing. Our results support further
      exploring the cholinergic anti-inflammatory pathway for preventing cisplatin
      induced AKI.

PMID- 29190777
TI  - Embedding resilience in the design of the electricity supply for industrial
      clients.
AB  - This paper proposes an optimization model, using Mixed-Integer Linear Programming
      (MILP), to support decisions related to making investments in the design of power
      grids serving industrial clients that experience interruptions to their energy
      supply due to disruptive events. In this approach, by considering the
      probabilities of the occurrence of a set of such disruptive events, the model is
      used to minimize the overall expected cost by determining an optimal strategy
      involving pre- and post-event actions. The pre-event actions, which are
      considered during the design phase, evaluate the resilience capacity (absorption,
      adaptation and restoration) and are tailored to the context of industrial clients
      dependent on a power grid. Four cases are analysed to explore the results of
      different probabilities of the occurrence of disruptions. Moreover, two
      scenarios, in which the probability of occurrence is lowest but the consequences
      are most serious, are selected to illustrate the model's applicability. The
      results indicate that investments in pre-event actions, if implemented, can
      enhance the resilience of power grids serving industrial clients because the
      impacts of disruptions either are experienced only for a short time period or are
      completely avoided.

PMID- 29190776
TI  - Large-scale identification of human cerebrovascular proteins: Inter-tissue and
      intracerebral vascular protein diversity.
AB  - The human cerebrovascular system is responsible for regulating demand-dependent
      perfusion and maintaining the blood-brain barrier (BBB). In addition, defects in
      the human cerebrovasculature lead to stroke, intracerebral hemorrhage, vascular
      malformations, and vascular cognitive impairment. The objective of this study was
      to discover new proteins of the human cerebrovascular system using expression
      data from the Human Protein Atlas, a large-scale project which allows public
      access to immunohistochemical analysis of human tissues. We screened 20,158
      proteins in the HPA and identified 346 expression patterns correlating to blood
      vessels in human brain. Independent experiments showed that 51/52 of these
      distributions could be experimentally replicated across different brain samples.
      Some proteins (40%) demonstrated endothelial cell (EC)-enriched expression, while
      others were expressed primarily in vascular smooth muscle cells (VSMC; 18%); 39%
      of these proteins were expressed in both cell types. Most brain EC markers were
      tissue oligospecific; that is, they were expressed in endothelia in an average of
      4.8 out of 9 organs examined. Although most markers expressed in endothelial
      cells of the brain were present in all cerebral capillaries, a significant number
      (21%) were expressed only in a fraction of brain capillaries within each brain
      sample. Among proteins found in cerebral VSMC, virtually all were also expressed
      in peripheral VSMC and in non-vascular smooth muscle cells (SMC). Only one was
      potentially brain specific: VHL (Von Hippel-Lindau tumor suppressor). HRC
      (histidine rich calcium binding protein) and VHL were restricted to VSMC and not
      found in non-vascular tissues such as uterus or gut. In conclusion, we define a
      set of brain vascular proteins that could be relevant to understanding the unique
      physiology and pathophysiology of the human cerebrovasculature. This set of
      proteins defines inter-organ molecular differences in the vasculature and
      confirms the broad heterogeneity of vascular cells within the brain.

PMID- 29190779
TI  - Manifold absolute pressure estimation using neural network with hybrid training
      algorithm.
AB  - In a modern small gasoline engine fuel injection system, the load of the engine
      is estimated based on the measurement of the manifold absolute pressure (MAP)
      sensor, which took place in the intake manifold. This paper present a more
      economical approach on estimating the MAP by using only the measurements of the
      throttle position and engine speed, resulting in lower implementation cost. The
      estimation was done via two-stage multilayer feed-forward neural network by
      combining Levenberg-Marquardt (LM) algorithm, Bayesian Regularization (BR)
      algorithm and Particle Swarm Optimization (PSO) algorithm. Based on the results
      found in 20 runs, the second variant of the hybrid algorithm yields a better
      network performance than the first variant of hybrid algorithm, LM, LM with BR
      and PSO by estimating the MAP closely to the simulated MAP values. By using a
      valid experimental training data, the estimator network that trained with the
      second variant of the hybrid algorithm showed the best performance among other
      algorithms when used in an actual retrofit fuel injection system (RFIS). The
      performance of the estimator was also validated in steady-state and transient
      condition by showing a closer MAP estimation to the actual value.

PMID- 29190778
TI  - MiR-6835 promoted LPS-induced inflammation of HUVECs associated with the
      interaction between TLR-4 and AdipoR1 in lipid rafts.
AB  - BACKGROUND: High mortality rate of critically-ill patients could be induced by
      sepsis and septic shock, which is the extremely life threatening. The purpose of
      this work is to identify and evaluate the potential regulatory mechanism of LPS
      induced inflammation associated with miR-6835 and lipid rafts in HUVECs. METHODS:
      The 3' UTR luciferase activity of AdipoR1 was detected, which was predicted the
      potential target gene of miR-6835. Moreover, the treated HUVECs with or without
      inhibitors or mimics of miR-6835 were used. Furthermore, the bio-functions of
      HUVECs were explored. The protein expression levels of SIRT-1, AMPK, and AdipoR1
      were assessed, which were involved in the AdipoR1 signaling pathway. Then, the
      interaction between TLR-4 and AdipoR1 in lipid rafts and its mediation role on
      LPS-induced inflammation was investigated in HUVECs. RESULTS: MiR-6835 targeted
      directly on AdipoR1, and suppressed its expression in mRNA (mimics of miR-6835:
      0.731+/-0.016 vs control: 1.527+/-0.015, P<0.001) and proteins levels, then
      regulated protein expression of SIRT-1 and AMPK, which were the downstream target
      genes of AdipoR1 signaling pathway. MiR-6835 enhanced LPS-induced inflammation
      process in HUVECs (TNF-alpha: LPS+mimics of miR-6835: 1638.51+/-78.43 vs LPS:
      918.73+/-39.73, P<0.001; IL-6: LPS+mimics of miR-6835: 1249.35+/-69.51 vs LPS:
      687.52+/-43.64, P<0.001), which was associated with the interaction between TLR-4
      and AdipoR1 in lipid rafts. CONCLUSIONS: MiR-6835 is the key regulator of LPS
      induced inflammation process in HUVECs. The interaction between TLR-4 and AdipoR1
      mediated by lipid rafts at membrane of HUVECs with inflammation process induced
      by miR-6835. Our results demonstrated a hopeful strategy for treatment on sepsis
      by aiming at lipid rafts and miR-6835.

PMID- 29190780
TI  - Characterization of thermostable alkaline proteases from Bacillus infantis SKS1
      isolated from garden soil.
AB  - Proteases are one of the largest groups of hydrolytic enzymes constituting about
      60% of total worldwide sales of industrial enzymes due to their wide applications
      in detergent, leather, textile, food and pharmaceutical industry. Microbial
      proteases have been preferred over animal and plant proteases because of their
      fundamental features and ease in production. Bacillus infantis SKS1, an alkaline
      protease producing bacteria has been isolated from garden soil of north India and
      identified using morphological, biochemical and molecular methods. 16S rDNA
      sequence amplified using universal primers has 99% sequence identity with
      corresponding gene sequence of Bacillus infantis strain FM 34 and Bacillus sp.
      Beige. The bacterial culture and its 16S rDNA gene sequence have been deposited
      to Microbial Culture Collection (Pune, India) with accession number MCC 3035 and
      GenBank with accession number KR092197 respectively. The partially purified
      extract of Bacillus infantis SKS1 was thermostable and active in presence of
      Mg2+, acetyl acetone and laundry detergents implicating its application in
      industry. Production of these enzymes using this strain was maximized by
      optimization of various parameters including temperature, pH, media components
      and other growth conditions. Our results show that fructose and dextrose serve as
      the best carbon sources for production of these enzymes, highlighting the use of
      this strain for enzyme production utilizing relatively inexpensive substrates
      like beet molasses and corn steep liquor. Additionally, this strain showed
      maximum production of enzymes at 40 degrees C similar to bacterial species used
      for commercial production of alkaline proteases. Characterization of alkaline
      proteases from this strain of Bacillus infantis and optimization of parameters
      for its production would help in understanding its industrial application and
      large-scale production.

PMID- 29190782
TI  - Addressing the cost of infractions in the online literature and databases.
AB  - Myocardial infarction sometimes appears misspelt as myocardial infraction in the
      cardiovascular research literature. With accurate citation of literature
      contributions important to advancing the field and its contributors, in this
      study we aimed to document the frequency and explore the causes and impact of
      this error specific to the cardiology literature. Literature databases (PubMed,
      Scopus, Web of Science, WIPO, Google Scholar, Google) were searched to identify
      the rate of myocardial infraction errors and found an error rate between 0.2% and
      1.6%, with substantial differences between search tools used. A Scopus search was
      used to show changes in errors over time, differences between journals and by
      specific authors. Myocardial infraction occurred at increasing annual rates over
      time and at higher rates than other errors. Increasing error rates were
      associated with increased volume of searchable material rather than quality of
      the literature. Transcription from article to database is a common source of
      error and some databases have higher rates of these errors. Simple measures to
      avoid and to correct these errors in the literature and the databases are also
      discussed.

PMID- 29190781
TI  - Roles of CD34+ cells and ALK5 signaling in the reconstruction of seminiferous
      tubule-like structures in 3-D re-aggregate culture of dissociated cells from
      neonatal mouse testes.
AB  - Tissue reconstruction in vitro can provide, if successful, a refined and simple
      system to analyze the underlying mechanisms that drive the morphogenesis and
      maintain the ordered structure. We have recently succeeded in reconstruction of
      seminiferous cord-like and tubule-like structures using 3-D re-aggregate culture
      of dissociated testicular cells. In testis formation, endothelial cells that
      migrated from mesonephroi to embryonic gonads have been shown to be critical for
      development of testis cords, but how endothelial cells contribute to testis cord
      formation remains unknown. To decipher the roles of endothelial and peritubular
      cells in the reconstruction of cord-like and tubule-like structures, we
      investigated the behavior of CD34+ endothelial and p75+ cells, and peritubular
      myoid cells (PTMCs) in 3-D re-aggregate cultures of testicular cells. The results
      showed that these 3 types of cells had the capacity of re-aggregation on their
      own and with each other, and of segregation into 3 layers in a re-aggregate,
      which were very similar to interstitial and peritubular tissues in vivo.
      Observation of behaviors of fluorescent Sertoli cells and other non-fluorescent
      types of cells using testes from Sox9-EGFP transgenic mice showed dynamic cell
      movement and segregation in re-aggregate cultures. Cultures of testicular cells
      deprived of interstitial and peritubular cells resulted in dysmorphic structures,
      but re-addition of them restored tubule-like structures. Purified CD34+ cells in
      culture differentiated into p75+ cells and PTMCs. These results indicate that
      CD34+ cells differentiate into p75+ cells, which then differentiate into PTMCs.
      TGFbeta signaling inhibitors, SB431542 and ALK5i, disturbed the reconstruction of
      cord-like and tubule-like structures, and the latter compromised re-construction
      of interstitial-like and peritubular-like structures, as well as the
      proliferation of CD34+, p75+, PTMCs, and Sertoli cells, and their movement and
      differentiation. These results indicate that CD34+ cells and signaling through
      ALK5 play pivotal roles in the morphogenesis of interstitial-like, peritubular
      like and cord-like structures.

PMID- 29190783
TI  - Satellite imagery-based monitoring of archaeological site damage in the Syrian
      civil war.
AB  - Since the start of the Syrian civil war in 2011, the rich archaeological heritage
      of Syria and northern Iraq has faced severe threats, including looting, combat
      related damage, and intentional demolition of monuments. However, the
      inaccessibility of the conflict zone to archaeologists or cultural heritage
      specialists has made it difficult to produce accurate damage assessments,
      impeding efforts to develop mitigation strategies and policies. This paper
      presents results of a project, undertaken in collaboration with the American
      Schools of Oriental Research (ASOR) and the US Department of State, to monitor
      damage to archaeological sites in Syria, northern Iraq, and southern Turkey using
      recent, high-resolution satellite imagery. Leveraging a large database of
      archaeological and heritage sites throughout the region, as well as access to
      continually updated satellite imagery from DigitalGlobe, this project has
      developed a flexible and efficient methodology to log observations of damage in a
      manner that facilitates spatial and temporal queries. With nearly 5000 sites
      carefully evaluated, analysis reveals unexpected patterns in the timing,
      severity, and location of damage, helping us to better understand the evolving
      cultural heritage crisis in Syria and Iraq. Results also offer a model for future
      remote sensing-based archaeological and heritage monitoring efforts in the Middle
      East and beyond.

PMID- 29190784
TI  - HIV transmission and pre-exposure prophylaxis in a high risk MSM population: A
      simulation study of location-based selection of sexual partners.
AB  - OBJECTIVE: In France, indications for pre-exposure prophylaxis (PrEP) for HIV
      prevention are based on individual-level risk factors for HIV infection. However,
      the risk of HIV infection may also depend on characteristics of sexual
      partnerships. Here we study how place-based selection of partners change
      transmission and the overall efficiency of PrEP. METHODS: We used the PREVAGAY
      survey of sexual behavior and HIV serostatus in men who have sex with men (MSM)
      in a Parisian district to look for associations between sexual network
      characteristics and HIV infection. We then simulated HIV transmission in a high
      risk MSM population. We used information about venues visited to meet casual
      sexual partners (clubs, backrooms or saunas) to define sexual networks. We then
      simulated HIV transmission in these networks and assessed the impact of PrEP in
      this population. RESULTS: In the PREVAGAY study, we found that HIV serostatus
      changed with the type of venues visited, in addition to other individual risk
      factors. In simulations, we found similar differences in HIV incidence when the
      choice of venues visited was not random. The use of PrEP allowed reducing
      incidence, irrespective of the venues visited by PrEP users. However, with the
      same amount of PrEP, the number of infections adverted could almost double
      depending on network structure and venues visited by PrEP users. CONCLUSION: This
      study shows that characteristics of the sexual network structure can strongly
      impact the effectiveness of PrEP interventions. These should be considered
      further to refine individual risk assessment and maximize the effect of
      individual-based prevention policies.

PMID- 29190785
TI  - Inclusion of periodontal ligament fibres in mandibular finite element models
      leads to an increase in alveolar bone strains.
AB  - Alveolar bone remodelling is vital for the success of dental implants and
      orthodontic treatments. However, the underlying biomechanical mechanisms, in
      particular the function of the periodontal ligament (PDL) in bone loading and
      remodelling, are not well understood. The PDL is a soft fibrous connective tissue
      that joins the tooth root to the alveolar bone and plays a critical role in the
      transmission of loads from the tooth to the surrounding bone. However, due to its
      complex structure, small size and location within the tooth socket it is
      difficult to study in vivo. Finite element analysis (FEA) is an ideal tool with
      which to investigate the role of the PDL, however inclusion of the PDL in FE
      models is complex and time consuming, therefore consideration must be given to
      how it is included. The aim of this study was to investigate the effects of
      including the PDL and its fibrous structure in mandibular finite element models.
      A high-resolution model of a human molar region was created from micro-computed
      tomography scans. This is the first time that the fibrous structure of the PDL
      has been included in a model with realistic tooth and bone geometry. The results
      show that omission of the PDL creates a more rigid model, reducing the strains
      observed in the mandibular corpus which are of interest when considering
      mandibular functional morphology. How the PDL is modelled also affects the
      strains. The inclusion of PDL fibres alters the strains in the mandibular bone,
      increasing the strains in the tooth socket compared to PDL modelled without
      fibres. As strains in the alveolar bone are thought to play a key role in bone
      remodelling during orthodontic tooth movement, future FE analyses aimed at
      improving our understanding and management of orthodontic treatment should
      include the fibrous structure of the PDL.

PMID- 29190786
TI  - Unsupervised morphological segmentation of tissue compartments in
      histopathological images.
AB  - Algorithmic segmentation of histologically relevant regions of tissues in
      digitized histopathological images is a critical step towards computer-assisted
      diagnosis and analysis. For example, automatic identification of epithelial and
      stromal tissues in images is important for spatial localisation and guidance in
      the analysis and characterisation of tumour micro-environment. Current
      segmentation approaches are based on supervised methods, which require extensive
      training data from high quality, manually annotated images. This is often
      difficult and costly to obtain. This paper presents an alternative data
      independent framework based on unsupervised segmentation of oropharyngeal cancer
      tissue micro-arrays (TMAs). An automated segmentation algorithm based on
      mathematical morphology is first applied to light microscopy images stained with
      haematoxylin and eosin. This partitions the image into multiple binary 'virtual
      cells', each enclosing a potential 'nucleus' (dark basins in the haematoxylin
      absorbance image). Colour and morphology measurements obtained from these virtual
      cells as well as their enclosed nuclei are input into an advanced unsupervised
      learning model for the identification of epithelium and stromal tissues. Here we
      exploit two Consensus Clustering (CC) algorithms for the unsupervised recognition
      of tissue compartments, that consider the consensual opinion of a group of
      individual clustering algorithms. Unlike most unsupervised segmentation analyses,
      which depend on a single clustering method, the CC learning models allow for more
      robust and stable detection of tissue regions. The proposed framework performance
      has been evaluated on fifty-five hand-annotated tissue images of oropharyngeal
      tissues. Qualitative and quantitative results of the proposed segmentation
      algorithm compare favourably with eight popular tissue segmentation strategies.
      Furthermore, the unsupervised results obtained here outperform those obtained
      with individual clustering algorithms.

PMID- 29190787
TI  - Magnification of digital hip radiographs differs between clinical workplaces.
AB  - Preoperative planning for total hip arthroplasty includes templating on
      anteroposterior radiographs. It is necessary to consider radiographic
      magnification in order to scale templates accurately. Studies dealing with hip
      templating report different values of radiographic magnification. It is not clear
      if the observed difference in magnification between the studies is caused by
      variability in studied groups, methodology or instrumentation. We hypothesize
      that there is a difference in magnification between clinical workplaces. Within
      this study, radiographic magnification was estimated on 337 radiographs of
      patients after total hip surgery from five orthopaedic departments in the Czech
      Republic. Magnification was determined for each patient as a ratio between
      diameter of implanted femoral head measured on radiogram and its true size. One
      way ANOVA revealed significant differences in magnification between workplaces
      (F(4,332) = 132, p<=0.001). These results suggest that radiographic magnification
      depends on the workplace where it is taken or more precisely on radiographic
      device. It indicates potential limits in generalizability of results of studies
      dealing with preoperative planning accuracy to other institutions.

PMID- 29190788
TI  - Non-invasive assessment of pulsatile intracranial pressure with phase-contrast
      magnetic resonance imaging.
AB  - Invasive monitoring of pulsatile intracranial pressure can accurately predict
      shunt response in patients with idiopathic normal pressure hydrocephalus, but may
      potentially cause complications such as bleeding and infection. We tested how a
      proposed surrogate parameter for pulsatile intracranial pressure, the phase
      contrast magnetic resonance imaging derived pulse pressure gradient, compared
      with its invasive counterpart. In 22 patients with suspected idiopathic normal
      pressure hydrocephalus, preceding invasive intracranial pressure monitoring, and
      any surgical shunt procedure, we calculated the pulse pressure gradient from
      phase-contrast magnetic resonance imaging derived cerebrospinal fluid flow
      velocities obtained at the upper cervical spinal canal using a simplified Navier
      Stokes equation. Repeated measurements of the pulse pressure gradient were also
      undertaken in four healthy controls. Of 17 shunted patients, 16 responded,
      indicating high proportion of "true" normal pressure hydrocephalus in the patient
      cohort. However, there was no correlation between the magnetic resonance imaging
      derived pulse pressure gradient and pulsatile intracranial pressure (R = -.18, P
      = .43). Pulse pressure gradients were also similar in patients and healthy
      controls (P = .26), and did not differ between individuals with pulsatile
      intracranial pressure above or below established thresholds for shunt treatment
      (P = .97). Assessment of pulse pressure gradient at level C2 was therefore not
      found feasible to replace invasive monitoring of pulsatile intracranial pressure
      in selection of patients with idiopathic normal pressure hydrocephalus for
      surgical shunting. Unlike invasive, overnight monitoring, the pulse pressure
      gradient from magnetic resonance imaging comprises short-term pressure
      fluctuations only. Moreover, complexity of cervical cerebrospinal fluid flow and 
      pulsatility at the upper cervical spinal canal may render the pulse pressure
      gradient a poor surrogate marker for intracranial pressure pulsations.

PMID- 29190789
TI  - Consumption of minimally processed food is inversely associated with excess
      weight in adolescents living in an underdeveloped city.
AB  - BACKGROUND: The consumption of ultra-processed foods may be associated with the
      development of chronic diseases, both in adults and in children/adolescents. This
      consumption is growing worldwide, especially in low and middle-income countries.
      Nevertheless, its magnitude in small, poor cities from the countryside is not
      well characterized, especially in adolescents. This study aimed to assess the
      consumption of minimally processed, processed and ultra-processed foods by
      adolescents from a poor Brazilian city and to determine if it was associated with
      excess weight, high waist circumference and high blood pressure. METHODS: Cross
      sectional study, conducted at a public federal school that offers technical
      education together with high school, located in the city of Murici. Adolescents
      of both sexes and aged between 14-19 years old were included. Anthropometric
      characteristics (weight, height, waist circumference), blood pressure, and
      dietary intake data were assessed. Associations were calculated using Poisson
      regression models, adjusted by sex and age. RESULTS: At total, 249 adolescents
      were included, being 55.8% girls, with a mean age of 16 years-old. The
      consumption of minimally processed foods was inversely associated with excess
      weight (Adjusted Prevalence Ratio: 0.61, 95% Confidence Interval: [0.39-0.96], P
      = 0.03). Although the consumption of ultra-processed foods was not associated
      with excess weight, high blood pressure and high waist circumference, 46.2% of
      the sample reported eating these products more than weekly. CONCLUSION:
      Consumption of minimally processed food is inversely associated with excess
      weight in adolescents. Investments in nutritional education aiming the prevention
      of chronic diseases associated with the consumption of these foods are necessary.

PMID- 29190790
TI  - InDel marker based genetic differentiation and genetic diversity in traditional
      rice (Oryza sativa L.) landraces of Chhattisgarh, India.
AB  - Rice has been cultivating and utilizing by humans for thousands of years under
      diverse environmental conditions. Therefore, tremendous genetic differentiation
      and diversity has occurred at various agro-ecosystems. The significant indica
      japonica differentiation in rice provides great opportunities for its genetic
      improvement. In the present investigation, a total of 42 polymorphic InDel
      markers were used for differentiating 188 rice landraces and two local varieties
      of Chhattisgarh, India into indica and japonica related genotypes based on 'InDel
      molecular index'. Frequency of japonica alleles varied from 0.11 to 0.89 among
      landraces. Results revealed that 104 rice landraces have indica type genetic
      architecture along with three tested indica cultivars Swarna, Mahamaya and
      Rajeshwari. Another 60 landraces were placed under 'close to indica' type. It was
      found that three rice landraces i.e. Kalajeera, Kapri, Tulsimala were 'close to
      japonica' type and 21 landraces were 'intermediate' type. The result from the
      calculation of 'InDel molecular index' was further verified with STRUCTURE,
      AMOVA, PCA and cluster analysis. Population structure analysis revealed two
      genetically distinct populations within the 190 rice landraces/genotypes. Based
      on AMOVA, 'intermediate' type, 'close to japonica' type and Dongjinbyeo (a
      japonica cultivar from Republic of Korea) displayed significant genetic
      differentiation (phiPT = 0.642, P = 0.000) from 'indica' and 'close to indica'
      groups. The PCA scatter plot and dendrogram demonstrated a clear pattern of two
      major group differentiations. 'Close to japonica' type and 'intermediate' type
      landraces/genotypes were grouped with Dongjinbyeo and formed a separate cluster
      at 30% Jaccard's similarity level from rest of the landraces/genotypes which were
      'close to indica' or 'indica' type. Such a significant genetic differentiation
      among the locally adapted landraces could be exploited for the development of
      rice varieties introgressing higher yield potential and better plant types of
      japonica type as per the need of consumers and rice traders.

PMID- 29190791
TI  - Can self-testing increase HIV testing among men who have sex with men: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Globally, four out of ten individuals living with HIV have not been
      tested for HIV. Testing is especially important for men who have sex with men
      (MSM), among whom an increasing HIV epidemic has been identified in many regions
      of the world. As a supplement to site-based HIV testing services, HIV self
      testing (HIVST) provides a promising approach to promote HIV testing. However,
      evidence is scattered and not well-summarized on the effect of HIVST to improve
      HIV testing behaviors, especially for MSM. METHODS: Seven databases (PubMed, Web
      of Science, Cochrane Library, PsycINFO, CINAHL Plus, WanFang, and China National
      Knowledge Internet) and conference abstracts from six HIV/sexually transmitted
      infections conferences were searched from January 2000-April 2017. RESULTS: Of
      1,694 records retrieved, 23 studies were identified, 9 conducted in resource
      limited countries and 14 in high-income countries. The pooled results showed that
      HIVST increased HIV test frequency for MSM by one additional test in a 6-month
      period (mean difference = 0.88 [95% CI 0.52-1.24]). The pooled proportion of
      first-time testers among those who took HIVST was 18.7% (95% CI: 9.9-32.4)
      globally, with a rate 3.32 times higher in resource-limited country settings
      (32.9% [95% CI: 21.3-47.6]) than in high-income countries (9.9% [95% CI: 7.4
      13.8]). The pooled proportions included non-recent testers, 32.9% (95% CI: 28.1
      38.3); ever or currently married MSM, 16.7% (95% CI: 14.5-19.4); and HIV positive
      men, 3.8% (95% CI: 2.0-5.7) globally; 6.5% [95% CI: 0.38-12.3] in resource
      limited country settings; and 2.9% [95% CI: 2.0-5.0] in high-income countries).
      The rates reported for linkage to care ranged from 31.3% to 100%. CONCLUSIONS:
      HIVST could increase HIV testing frequency and potentially have capacity
      equivalent to that of site-based HIV testing services to reach first-time,
      delayed, married, and HIV-infected testers among MSM and link them to medical
      care. However, more rigorous study designs are needed to explore the specific
      self-testing approach (oral-fluid based or finger-prick based) on improving HIV
      testing for MSM in different social and economic settings.

PMID- 29190792
TI  - Molecular genetic diversity and population structure of Ethiopian white lupin
      landraces: Implications for breeding and conservation.
AB  - White lupin is one of the four economically important species of the Lupinus
      genus and is an important grain legume in the Ethiopian farming system. However,
      there has been limited research effort to characterize the Ethiopian white lupin
      landraces. Fifteen polymorphic simple sequence repeat (SSR) markers were used to
      assess the genetic diversity and population structure of 212 Ethiopian white
      lupin (Lupinus albus) landraces and two genotypes from different species (Lupinus
      angustifolius and Lupinus mutabilis) were used as out-group. The SSR markers
      revealed 108 different alleles, 98 of them from 212 landraces and 10 from out
      group genotypes, with an average of 6.5 alleles per locus. The average gene
      diversity was 0.31. Twenty eight landraces harbored one or more private alleles
      from the total of 28 private alleles identified in the 212 white lupin
      accessions. Seventy-seven rare alleles with a frequency of less than 5% were
      identified and accounted for 78.6% of the total alleles detected. Analysis of
      molecular variance (AMOVA) showed that 92% of allelic diversity was attributed to
      individual accessions within populations while only 8% was distributed among
      populations. At 70% similarity level, the UPGMA dendrogram resulted in the
      formation of 13 clusters comprised of 2 to 136 landraces, with the out-group
      genotypes and five landraces remaining distinct and ungrouped. Population
      differentiation and genetic distance were relatively high between Gondar and
      Ethiopian white lupin populations collected by Australians. A model-based
      population structure analysis divided the white lupin landraces into two
      populations. All Ethiopian white lupin landrace populations, except most of the
      landraces collected by Australians (77%) and about 44% from Awi, were grouped
      together with significant admixtures. The study also suggested that 34
      accessions, as core collections, were sufficient to retain 100% of SSR diversity.
      These accessions (core G-34) represent 16% of the whole 212 Ethiopian white lupin
      accessions and populations from West Gojam, Awi and Australian collections
      contributed more accessions to the core collection.

PMID- 29190793
TI  - Transcriptome analysis of WRKY gene family in Oryza officinalis Wall ex Watt and
      WRKY genes involved in responses to Xanthomonas oryzae pv. oryzae stress.
AB  - Oryza officinalis Wall ex Watt, a very important and special wild rice species,
      shows abundant genetic diversity and disease resistance features, especially high
      resistance to bacterial blight. The molecular mechanisms of bacterial blight
      resistance in O. officinalis have not yet been elucidated. The WRKY transcription
      factor family is one of the largest gene families involved in plant growth,
      development and stress response. However, little is known about the numbers,
      structure, molecular phylogenetics, and expression of the WRKY genes under
      Xanthomonas oryzae pv. oryzae (Xoo) stress in O. officinalis due to lacking of O.
      officinalis genome. Therefore, based on the RNA-sequencing data of O.
      officinalis, we performed a comprehensive study of WRKY genes in O. officinalis
      and identified 89 OoWRKY genes. Then 89 OoWRKY genes were classified into three
      groups based on the WRKY domains and zinc finger motifs. Phylogenetic analysis
      strongly supported that the evolution of OoWRKY genes were consistent with
      previous studies of WRKYs, and subgroup IIc OoWRKY genes were the original
      ancestors of some group II and group III OoWRKYs. Among the 89 OoWRKY genes,
      eight OoWRKYs displayed significantly different expression (>2-fold, p<0.01) in
      the O. officinalis transcriptome under Xoo strains PXO99 and C5 stress 48 h,
      suggesting these genes might play important role in PXO99 and C5 stress responses
      in O. officinalis. QRT-PCR analysis and confirmation of eight OoWRKYs expression
      patterns revealed that they responded strongly to PXO99 and C5 stress 24 h, 48 h,
      and 72 h, and the trends of these genes displaying marked changes were consistent
      with the 48 h RNA-sequencing data, demonstrated these genes played important
      roles in response to biotic stress and might even involved in the bacterial
      blight resistance. Tissue expression profiles of eight OoWRKY genes revealed that
      they were highly expressed in root, stem, leaf, and flower, especially in leaf
      (except OoWRKY71), suggesting these genes might be also important for plant
      growth and organ development. In this study, we analyzed the WRKY family of
      transcription factors in O.officinalis. Insight was gained into the
      classification, evolution, and function of the OoWRKY genes, revealing the
      putative roles of eight significantly different expression OoWRKYs in Xoo strains
      PXO99 and C5 stress responses in O.officinalis. This study provided a better
      understanding of the evolution and functions of O. officinalis WRKY genes, and
      suggested that manipulating eight significantly different expression OoWRKYs
      would enhance resistance to bacterial blight.

PMID- 29190794
TI  - 3D collagen fibrillar microstructure guides pancreatic cancer cell phenotype and
      serves as a critical design parameter for phenotypic models of EMT.
AB  - Pancreatic cancer, one of the deadliest cancers, is characterized by high rates
      of metastasis and intense desmoplasia, both of which are associated with changes
      in fibrillar type I collagen composition and microstructure. Epithelial to
      mesenchymal transition (EMT), a critical step of metastasis, also involves a
      change in extracellular matrix (ECM) context as cells detach from basement
      membrane (BM) and engage interstitial matrix (IM). The objective of this work was
      to develop and apply an in-vitro three-dimensional (3D) tumor-ECM model to define
      how ECM composition and biophysical properties modulate pancreatic cancer EMT.
      Three established pancreatic ductal adenocarcinoma (PDAC) lines were embedded
      within 3D matrices prepared with type I collagen Oligomer (IM) at various fibril
      densities to control matrix stiffness or Oligomer and Matrigel combined at
      various ratios while maintaining constant matrix stiffness. Evaluation of cell
      morphology and protein expression at both the cellular- and population-levels
      revealed a spectrum of matrix-driven EMT phenotypes that were dependent on ECM
      composition and architecture as well as initial PDAC phenotype. In general,
      exposure to fibrillar IM was sufficient to drive EMT, with cells displaying
      spindle-shaped morphology and mesenchymal markers, and non-fibrillar BM promoted
      more epithelial behavior. When cultured within low density Oligomer, only a
      subpopulation of epithelial BxPC-3 cells displayed EMT while mesenchymal MiaPaCa
      2 cells displayed more uniform spindle-shaped morphologies and mesenchymal marker
      expression. Interestingly, as IM fibril density increased, associated changes in
      spatial constraints and matrix stiffness resulted in all PDAC lines growing as
      tight clusters; however mesenchymal marker expression was maintained.
      Collectively, the comparison of these results to other in-vitro tumor models
      highlights the role of IM fibril microstructure in guiding EMT heterogeneity and
      showcases the potential of standardized 3D matrices such as Oligomer to serve as
      robust platforms for mechanistic study of metastasis and creation of predictive
      drug screening models.

PMID- 29190796
TI  - Risk factors for the development of chronic pulmonary aspergillosis in patients
      with nontuberculous mycobacterial lung disease.
AB  - Nontuberculous mycobacterial lung disease (NTM-LD) is increasingly recognized as
      an important predisposing condition for the development of chronic pulmonary
      aspergillosis (CPA), but there are limited data on the risk factors for CPA
      development in NTM-LD patients. We reviewed the medical records of 566 patients
      who, at the time of diagnosis of NTM-LD, did not have CPA and who received >=12
      months of treatment for NTM-LD between January 2010 and June 2015. Of these
      patients, 41 (7.2%) developed CPA (NTM-CPA group), whereas the remaining 525
      patients did not develop CPA (NTM group). The median time to the development of
      CPA was 18.0 months from treatment initiation for NTM-LD. The NTM-CPA group was
      older and had significantly higher proportions of males, current smokers, and
      patients with a low body mass index (<18.5 kg/m2), when compared to the NTM
      group. Moreover, the NTM-CPA group was more likely to have a history of
      tuberculosis and chronic obstructive lung disease and to have used inhaled or
      systemic steroids. In the NTM-CPA group, more than 40% of patients had
      Mycobacterium abscessus complex (MABC) as the cause of NTM-LD, and the
      fibrocavitary form of NTM-LD was the most common; both associations were higher
      than in the NTM group. Overall, 17 (3%) patients died, and the NTM-CPA group had
      a higher mortality rate than did the NTM group (19.5% vs. 1.7%, respectively;
      P<0.001). In a multivariable analysis, old age, male gender, low body mass index,
      chronic obstructive lung disease, systemic steroids, MABC as the etiologic
      organism, and the fibrocavitary form of NTM-LD remained significant predictors of
      development of CPA. In conclusion, CPA occurred in 7.2% of patients after
      initiation of treatment for NTM-LD, and some risk factors were associated with
      CPA development. Given the worse prognosis, early diagnosis and treatment of CPA
      are important in patients with NTM-LD.

PMID- 29190795
TI  - Expression of phosphatase of regenerating liver (PRL)-3, is independently
      associated with biochemical failure, clinical failure and death in prostate
      cancer.
AB  - BACKGROUND: Prostate cancer (PC) stratification needs new prognostic tools to
      reduce overtreatment. Phosphatase of regenerating liver (PRL-3) is a phosphatase
      found at high levels in several cancer types, where its expression is associated
      with survival. A recent PC cell line study has shown it to be involved in PC
      growth and migration. METHODS: We used a monoclonal antibody to evaluate the
      expression of PRL-3 in PC tissue of patients in an unselected cohort of 535
      prostatectomy patients. We analyzed associations between PRL-3 expression and
      biochemical failure-free survival (BFFS), clinical failure-free survival (CFFS)
      and PC death-free survival (PCDFS). RESULTS: Cytoplasmic PRL-3 staining in tumor
      cells was significantly correlated to expression of molecules in the VEGFR-axis,
      but not to the clinicopathological variables. High PRL-3 was not significantly
      associated with survival in the univariate analysis for BFFS (p = 0.131), but
      significantly associated with CFFS (p = 0.044) and PCDFS (p = 0.041). In
      multivariate analysis for the various end points, PRL-3 came out as an
      independent and significant indicator of poor survival for BFFS (HR = 1.53, CI95%
      1.10-2.13, p = 0.012), CFFS (HR = 2.41, CI95% 1.17-4.98, p = 0.017) and PCDFS (HR
      = 3.99, CI95% 1.21-13.1, p = 0.023). CONCLUSIONS: PRL-3 is independently
      associated with all PC endpoints in this study. Since high PRL-3 expression also
      correlates with poor prognosis in other cancers and functional studies in PC
      support these findings, PRL-3 emerges as a potential treatment target in PC.

PMID- 29190797
TI  - Topographic characteristics after Descemet's membrane endothelial keratoplasty
      and Descemet's stripping automated endothelial keratoplasty.
AB  - PURPOSE: To investigate the topographic characteristics of the posterior corneal
      surface after Descemet's endothelial membrane keratoplasty (DMEK) and Descemet's
      stripping automated endothelial keratoplasty (DSAEK) and their effects on
      postoperative visual acuity. METHODS: Nineteen eyes of 19 patients after DMEK, 23
      eyes of 23 patients after DSAEK, and 18 eyes of 18 control subjects were
      retrospectively analyzed. Best spectacle-corrected visual acuity (BSCVA),
      aberration factors (higher-order aberrations [HOAs], spherical aberrations [SAs],
      and coma aberrations [Comas] at 6.0 mm) were evaluated preoperatively and at 1,
      3, and 6 months postoperatively. The posterior refractive pattern of the
      topography map was classified into 5 grades (0-5) (posterior color grade) using
      anterior segment optical coherence tomography. Correlations between BSCVA and
      some factors (abbreviation factors, posterior color grade) were analyzed.
      RESULTS: BSCVA was significantly better after DMEK than after DSAEK (P < 0.001).
      Posterior HOAs, SAs, and Comas after each type of endothelial keratoplasty were
      significantly greater compared to control (P < 0.01). Posterior HOAs,
      total/anterior/posterior SAs, and posterior color grade were significantly lower
      in the DMEK group than in the DSAEK group at 3 months (P < 0.024 [posterior
      HOAs], P = 0.047 [total SA], P < 0.001 [anterior SAs], P = 0.021 [posterior SAs],
      and P < 0.001 [posterior color grade]) and 6 months postoperatively (P = 0.034
      [posterior HOAs], P < 0.001 [total SAs], P < 0.001 [anterior SAs], P = 0.013
      [posterior SAs], and P = 0.004 [posterior color grade]). BSCVA was significantly
      correlated with HOAs, SAs, and posterior color grade (P < 0.001 for all except
      anterior HOAs [P = 0.004]). CONCLUSIONS: High posterior color grades were
      associated with larger aberration factors and had a negative effect on visual
      function after endothelial keratoplasty. Rapid improvement of visual function
      after DMEK may be attributed to less change at the posterior surface.

PMID- 29190798
TI  - Human pleural fluid is a potent growth medium for Streptococcus pneumoniae.
AB  - Empyema is defined by the presence of bacteria and/or pus in pleural effusions.
      However, the biology of bacteria within human pleural fluid has not been studied.
      Streptococcus pneumoniae is the most common cause of pediatric and frequent cause
      of adult empyema. We investigated whether S. pneumoniae can proliferate within
      human pleural fluid and if growth is affected by the cellular content of the
      fluid and/or characteristics of pneumococcal surface proteins. Invasive S.
      pneumoniae isolates (n = 24) and reference strain recovered from human blood or
      empyema were inoculated (1.5*106CFU/mL) into sterile human malignant pleural
      fluid samples (n = 11). All S. pneumoniae (n = 25) strains proliferated rapidly,
      increasing by a median of 3009 (IQR 1063-9846) from baseline at 24hrs in all
      pleural effusions tested. Proliferation was greater than in commercial
      pneumococcal culture media and concentrations were maintained for 48hrs without
      autolysis. A similar magnitude of proliferation was observed in pleural fluid
      before and after removal of its cellular content, p = 0.728. S. pneumoniae (D39
      strain) wild-type, and derivatives (n = 12), each with mutation(s) in a different
      gene required for full virulence were inoculated into human pleural fluid (n =
      8). S. pneumoniae with pneumococcal surface antigen A (DeltapsaA) mutation failed
      to grow (2207-fold lower than wild-type), p<0.001, however growth was restored
      with manganese supplementation. Growth of other common respiratory pathogens (n =
      14) across pleural fluid samples (n = 7) was variable and inconsistent, with some
      strains failing to grow. We establish for the first time that pleural fluid is a
      potent growth medium for S. pneumoniae and proliferation is dependent on the PsaA
      surface protein and manganese.

PMID- 29190799
TI  - Detecting event-related changes in organizational networks using optimized neural
      network models.
AB  - Organizational external behavior changes are caused by the internal structure and
      interactions. External behaviors are also known as the behavioral events of an
      organization. Detecting event-related changes in organizational networks could
      efficiently be used to monitor the dynamics of organizational behaviors. Although
      many different methods have been used to detect changes in organizational
      networks, these methods usually ignore the correlation between the internal
      structure and external events. Event-related change detection considers the
      correlation and could be used for event recognition based on social network
      modeling and supervised classification. Detecting event-related changes could be
      effectively useful in providing early warnings and faster responses to both
      positive and negative organizational activities. In this study, event-related
      change in an organizational network was defined, and artificial neural network
      models were used to quantitatively determine whether and when a change occurred.
      To achieve a higher accuracy, Back Propagation Neural Networks (BPNNs) were
      optimized using Genetic Algorithms (GAs) and Particle Swarm Optimization (PSO).
      We showed the feasibility of the proposed method by comparing its performance
      with that of other methods using two cases. The results suggested that the
      proposed method could identify organizational events based on a correlation
      between the organizational networks and events. The results also suggested that
      the proposed method not only has a higher precision but also has a better
      robustness than the previously used techniques.

PMID- 29190800
TI  - ERRalpha protein is stabilized by LSD1 in a demethylation-independent manner.
AB  - The LSD1 histone demethylase is highly expressed in breast tumors where it
      constitutes a factor of poor prognosis and promotes traits of cancer
      aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen
      Related Receptor alpha (ERRalpha) induces LSD1 to demethylate the Lys 9 of
      histone H3. This results in the transcriptional activation of a number of common
      target genes, several of which being involved in cellular invasion. High
      expression of ERRalpha protein is also a factor of poor prognosis in breast
      tumors. Here we show that, independently of its demethylase activities, LSD1
      protects ERRalpha from ubiquitination, resulting in overexpression of the latter
      protein. Our data also suggests that the elevation of LSD1 mRNA and protein in
      breast cancer (as compared to normal tissue) may be a key event to increase
      ERRalpha protein, independently of its corresponding mRNA.

PMID- 29190801
TI  - Comparison between manual and mechanical chest compressions during resuscitation
      in a pediatric animal model of asphyxial cardiac arrest.
AB  - AIMS: Chest compressions (CC) during cardiopulmonary resuscitation are not
      sufficiently effective in many circumstances. Mechanical CC could be more
      effective than manual CC, but there are no studies comparing both techniques in
      children. The objective of this study was to compare the effectiveness of manual
      and mechanical chest compressions with Thumper device in a pediatric cardiac
      arrest animal model. MATERIAL AND METHODS: An experimental model of asphyxial
      cardiac arrest (CA) in 50 piglets (mean weight 9.6 kg) was used. Animals were
      randomized to receive either manual CC or mechanical CC using a pediatric piston
      chest compressions device (Life-Stat(r), Michigan Instruments). Mean arterial
      pressure (MAP), arterial blood gases and end-tidal CO2 (etCO2) values were
      measured at 3, 9, 18 and 24 minutes after the beginning of resuscitation.
      RESULTS: There were no significant differences in MAP, DAP, arterial blood gases
      and etCO2 between chest compression techniques during CPR. Survival rate was
      higher in the manual CC (15 of 30 = 50%) than in the mechanical CC group (3 of 20
      = 15%) p = 0.016. In the mechanical CC group there was a non significant higher
      incidence of haemorrhage through the endotracheal tube (45% vs 20%, p = 0.114).
      CONCLUSIONS: In a pediatric animal model of cardiac arrest, mechanical piston
      chest compressions produced lower survival rates than manual chest compressions,
      without any differences in hemodynamic and respiratory parameters.

PMID- 29190803
TI  - Correction: Risk of bias and confounding of observational studies of Zika virus
      infection: A scoping review of research protocols.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180220.].

PMID- 29190802
TI  - Perceiving the evil eye: Investigating hostile interpretation of ambiguous facial
      emotional expression in violent and non-violent offenders.
AB  - Research into the causal and perpetuating factors influencing aggression has
      partly focused on the general tendency of aggression-prone individuals to infer
      hostile intent in others, even in ambiguous circumstances. This is referred to as
      the 'hostile interpretation bias'. Whether this hostile interpretation bias also
      exists in basal information processing, such as perception of facial emotion, is
      not yet known, especially with respect to the perception of ambiguous
      expressions. In addition, little is known about how this potential bias in facial
      emotion perception is related to specific characteristics of aggression. In the
      present study, conducted in a penitentiary setting with detained male adults, we
      investigated if violent offenders (n = 71) show a stronger tendency to interpret
      ambiguous facial expressions on a computer task as angry rather than happy,
      compared to non-violent offenders (n = 14) and to a control group of healthy
      volunteers (n = 32). We also investigated if hostile perception of facial
      expressions is related to specific characteristics of aggression, such as
      proactive and reactive aggression. No clear statistical evidence was found that
      violent offenders perceived facial emotional expressions as more angry than non
      violent offenders or healthy volunteers. A regression analysis in the violent
      offender group showed that only age and a self-report measure of hostility
      predicted outcome on the emotion perception task. Other traits, such as
      psychopathic traits, intelligence, attention and a tendency to jump to
      conclusions were not associated with interpretation of anger in facial emotional
      expressions. We discuss the possible impact of the study design and population
      studied on our results, as well as implications for future studies.

PMID- 29190804
TI  - Virulence genes and subclone status as markers of experimental virulence in a
      murine sepsis model among Escherichia coli sequence type 131 clinical isolates
      from Spain.
AB  - OBJECTIVE: To assess experimental virulence among sequence type 131 (ST131)
      Escherichia coli bloodstream isolates in relation to virulence genotype and
      subclone. METHODS: We analysed 48 Spanish ST131 bloodstream isolates (2010) by
      PCR for ST131 subclone status (H30Rx, H30 non-Rx, or non-H30), virulence genes
      (VGs), and O-type. Then we compared these traits with virulence in a murine
      sepsis model, as measured by illness severity score (ISS) and rapid lethality
      (mean ISS >= 4). RESULTS: Of the 48 study isolates, 65% were H30Rx, 21% H30 non
      Rx, and 15% non-H30; 44% produced ESBLs, 98% were O25b, and 83% qualified as
      extraintestinal pathogenic E. coli (ExPEC). Of 49 VGs, ibeA and iss were
      associated significantly with non-H30 isolates, and sat, iha and malX with H30
      isolates. Median VG scores differed by subclone, i.e., 12 (H30Rx), 10 (H30 non
      Rx), and 11 (non-H30) (p < 0.01). Nearly 80% of isolates represented a described
      virotype. In mice, H30Rx and non-H30 isolates were more virulent than H30 non-Rx
      isolates (according to ISS [p = 0.03] and rapid lethality [p = 0.03]), as were
      ExPEC isolates compared with non-ExPEC isolates (median ISS, 4.3 vs. 2.7: p =
      0.03). In contrast, most individual VGs, VG scores, VG profiles, and virotypes
      were not associated with mouse virulence. CONCLUSIONS: ST131 subclone and ExPEC
      status, but not individual VGs, VG scores or profiles, or virotypes, predicted
      mouse virulence. Given the lower virulence of non-Rx H30 isolates, hypervirulence
      probably cannot explain the ST131-H30 clade's epidemic emergence.

PMID- 29190805
TI  - Single-molecule study of full-length NaChBac by planar lipid bilayer recording.
AB  - Planar lipid bilayer device, alternatively known as BLM, is a powerful tool to
      study functional properties of conducting membrane proteins such as ion channels
      and porins. In this work, we used BLM to study the prokaryotic voltage-gated
      sodium channel (Nav) NaChBac in a well-defined membrane environment. Navs are an
      essential component for the generation and propagation of electric signals in
      excitable cells. The successes in the biochemical, biophysical and
      crystallographic studies on prokaryotic Navs in recent years has greatly promoted
      the understanding of the molecular mechanism that underlies these proteins and
      their eukaryotic counterparts. In this work, we investigated the single-molecule
      conductance and ionic selectivity behavior of NaChBac. Purified NaChBac protein
      was first reconstituted into lipid vesicles, which is subsequently incorporated
      into planar lipid bilayer by fusion. At single-molecule level, we were able to
      observe three distinct long-lived conductance sub-states of NaChBac. Change in
      the membrane potential switches on the channel mainly by increasing its opening
      probability. In addition, we found that individual NaChBac has similar
      permeability for Na+, K+, and Ca2+. The single-molecule behavior of the full
      length protein is essentially highly stochastic. Our results show that planar
      lipid bilayer device can be used to study purified ion channels at single
      molecule level in an artificial environment, and such studies can reveal new
      protein properties that are otherwise not observable in in vivo ensemble studies.

PMID- 29190806
TI  - Size-conditional smolting and the response of Carmel River steelhead to two
      decades of conservation efforts.
AB  - Threshold effects are common in ecosystems and can generate counterintuitive
      outcomes in management interventions. A threshold effect proposed for steelhead
      trout (Oncorhynchus mykiss) is size-conditional smolting and marine survival.
      Steelhead are anadromous, maturing in the ocean but migrating to freshwater to
      spawn, where their offspring reside for one or more years before smolting
      physiologically transforming to a saltwater form-and migrating to the ocean. In
      conditional smolting, juveniles transform only if growth exceeds a threshold body
      size prior to migration season, and subsequent marine survival correlates with
      size at ocean entry. Conditional smolting suggests that efforts to improve
      freshwater survival of juveniles may reduce smolt success if they increase
      competition and reduce growth. Using model-selection techniques, we asked if this
      effect explained declining numbers of adult Carmel River steelhead. This
      threatened population has been the focus of two decades of habitat restoration,
      as well as active translocation and captive-rearing of juveniles stranded in
      seasonally dewatered channels. In the top-ranked model selected by information
      theoretic criteria, adult decline was linked to reduced juvenile growth rates in
      the lower river, consistent with the conditional smolting hypothesis. According
      to model inference, since 2005 most returning adult steelhead were captively
      reared. However, a lower-ranked model without conditional smolting also had
      modest support, and suggested a negative effect of captive rearing.
      Translocations of juvenile fish to perennial reaches may have reduced the
      steelhead run slightly by raising competition, but this effect is confounded in
      the data with effects of river flow on growth. Efforts to recover Carmel River
      steelhead will probably be more successful if they focus on conditions promoting
      rapid growth in the river. Our analysis clearly favored a role for size
      conditional smolting and marine survival in the decline of the population, but
      did not definitively rule out alternative explanations.

PMID- 29190807
TI  - Identification of BLCAP as a novel STAT3 interaction partner in bladder cancer.
AB  - Bladder cancer associated protein (Blcap) expression is commonly down-regulated
      in invasive bladder cancer, and may have prognostic value given that its
      expression is negatively correlated with patient survival. We have previously
      investigated the expression patterns and cellular localization of Blcap in
      bladder cancer, where we found that about 20% of the lesions examined displayed
      strong nuclear expression of Blcap, and that this phenotype was associated with
      overall poor disease outcome. Here we report on the analysis of possible
      functional associations between nuclear expression of Blcap and canonical
      signaling pathways. We performed serial immunohistochemistry (IHC) analysis of
      bladder tissue samples, with serial sections stained with phospho-specific
      antibodies recognizing key signaling intermediates, such as P-Stat3, P-Akt, and P
      Erk1/2, among others, in an immunophenotyping approach we have established and
      reported previously. Using this approach, we found that nuclear localization of
      Blcap was associated with expression of P-Stat3. A parallel analysis, cytokine
      profiling of bladder tumor interstitial fluids of samples expressing (or not)
      Blcap, showed interleukin (IL)-6, IL-8, and monocyte chemotactic protein 1 (MCP
      1) to be correlated with nuclear expression of Blcap, independently supporting a
      role for Stat3 signaling in localization of Blcap. Multiple indirect
      immunofluorescence analysis of tissue biopsies confirmed that Blcap co-localized
      with Stat3. Furthermore, we could also demonstrate, using an in situ proximity
      ligation assay that Blcap and Stat3 are in close physical proximity of each other
      in bladder tissue, and that Blcap physically interacts with Stat3 as determined
      by co-immunoprecipitation of these proteins. Our data indicates that Blcap is a
      novel Stat3 interaction partner and suggests a role for Blcap in the Stat3
      mediated progression of precancerous lesions to invasive tumors of the bladder.

PMID- 29190808
TI  - The validity of linear and non-linear heart rate metrics as workload indicators
      of emergency physicians.
AB  - BACKGROUND: It has been shown that linear and non-linear heart rate variability
      (HRV) metrics are suitable to assess workload of anesthetists administering
      anesthesia. In pre-hospital emergency care, these parameters have not yet been
      evaluated. We hypothesized that heart rate (HR) and HRV metrics discriminate
      between differing workload levels of an emergency physician. METHODS:
      Electrocardiograms were obtained from 13 emergency physicians. Mean HR, ten
      linear and seven non-linear HRV metrics were analyzed. For each sortie, four
      different levels of workload were defined. Mixed-effects models and the area
      under the receiver operating characteristics curve (AUC) were used to test and
      quantify the HR and HRV metrics' ability to discriminate between levels of
      workload. This was conducted for mean HR and each HRV metric as well as for
      groups of metrics (time domain vs. frequency domain vs. non-linear metrics).
      RESULTS: The non-linear HRV metric Permutation entropy (PeEn) discriminated best
      between the time before the alarm and primary patient care (AUC = 0.998, 1st rank
      of 18 HRV metrics). In contrast, AUC of the mean HR was low (0.558, 17th rank).
      In the multivariable approach, the non-linear HRV metrics provided a higher AUC
      (0.998) compared to the frequency domain (0.677) and to the time domain metrics
      (0.680). CONCLUSION: Non-linear heart rate metrics and, specifically, PeEn
      provided good validity for the assessment of different levels of a physician's
      workload in the setting of pre-hospital emergency care. In contradiction to
      earlier findings, the physicians' mean HR was not a valid marker of workload.

PMID- 29190809
TI  - Molecular diagnosis of patients with epilepsy and developmental delay using a
      customized panel of epilepsy genes.
AB  - Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum
      that are associated with great genetic heterogeneity, thus making sequential
      single-gene testing an impractical basis for diagnostic strategy. The advent of
      next-generation sequencing has increased the success rate of epilepsy diagnosis,
      and targeted resequencing using genetic panels is the a most cost-effective
      choice. We report the results found in a group of 87 patients with epilepsy and
      developmental delay using targeted next generation sequencing (custom-designed
      Haloplex panel). Using this gene panel, we were able to identify disease-causing
      variants in 17 out of 87 (19.5%) analyzed patients, all found in known epilepsy
      associated genes (KCNQ2, CDKL5, STXBP1, SCN1A, PCDH19, POLG, SLC2A1, ARX, ALG13,
      CHD2, SYNGAP1, and GRIN1). Twelve of 18 variants arose de novo and 6 were novel.
      The highest yield was found in patients with onset in the first years of life,
      especially in patients classified as having early-onset epileptic encephalopathy.
      Knowledge of the underlying genetic cause provides essential information on
      prognosis and could be used to avoid unnecessary studies, which may result in a
      greater diagnostic cost-effectiveness.

PMID- 29190810
TI  - Aneurysmal subarachnoid haemorrhage (aSAH): Five consecutive years' experience of
      Fars province, Iran.
AB  - OBJECTIVE: Subarachnoid haemorrhage (SAH), caused by the rupture of intracranial
      aneurysms, is a devastating event with high rates of morbidity and mortality.
      Aneurysmal subarachnoid haemorrhage (aSAH) plays a critical role in the potential
      loss of life as its sufferers are usually of a young age. We aimed to investigate
      the incidence of aSAH along with the patients' characteristics over five
      consecutive years in Fars, a large province located in Southern Iran. METHODS: In
      this prospective study, anonymous data of all patients diagnosed with aSAH in
      Fars province were collected after patient admission and surgery. Data from the
      last national census in 2011 were used to calculate the incidence. The data were
      analysed using SPSS software version 18 using independent sample t test, chi
      square test and ANOVA. The significance level was set at 0.05. RESULTS: The
      number of aSAH cases identified in Fars, Iran, each year varied between 78 (2011)
      and 98 (2015) for a total of 421 aSAH cases within the 5-year study period. The
      annual aSAH incidence estimates showed no differences and were 1.65 [95%
      confidence interval (CI): 1.58-1.72], 1.70 (95%CI: 1.68-1.72), 1.71 (95%CI: 1.63
      1.78), 1.82 (95%CI: 1.74-1.9), and 2.05 (95%CI: 1.97-2.13) per 100,000 persons,
      respectively, for the five consecutive years from 21 March 2011 to 20 March 2016.
      Hypertension was the most common risk factor, and was found in 198 (48%) aSAH
      patients. Ninety-four (22.5%) patients had moderate hydrocephalus on admission.
      Middle cerebral artery and anterior communicating artery were the most common
      sites of aneurysms. On admission, 351 (83%) patients had a Glasgow Coma Scale
      score >7, 197 (47%) presented with Hunt and Hess score of 1, and 365 (87%) had a
      Fisher score of <=3. Multiple aneurysms were found in 59 (14%) of the 421 cases
      and the most common risk factors in multiple aneurysms were hypertension in 30
      (51%) and smoking in 26 (44%) cases. Survival data were available only on
      patients diagnosed in year 2015, and the six-month survival rate was 89.8%.
      CONCLUSIONS: This study revealed that although the incidence of aSAH remained
      stable, the survival of aSAH patients who reached the hospital alive and were
      operated on, improved in Shiraz (the six-month survival rate was 89.8% in year
      2015). The incidence and survival study on aSAH in other geographic areas of Iran
      as a multi-centre study is recommended. There is a need to inform primary
      healthcare workers regarding the possibility of aSAH in a patient with signs of
      the sentinel headache.

PMID- 29190812
TI  - Diagnostic performance of the (1-3)-beta-D-glucan assay in patients with
      Pneumocystis jirovecii compared with those with candidiasis, aspergillosis,
      mucormycosis, and tuberculosis, and healthy volunteers.
AB  - BACKGROUND: Diagnosis of pneumocystis pneumonia (PCP) relies on microscopic
      visualization of P. jirovecii, or detection of Pneumocystis DNA in respiratory
      specimens, which involves invasive procedures such as bronchoalveolar lavage. The
      (1-3)-beta-D-glucan (BG) assay has been proposed as a less invasive and less
      expensive diagnostic test to rule out PCP. We therefore compared blood levels of
      BG in patients with PCP with those of patients with candidemia, chronic
      disseminated candidiasis (CDC), invasive aspergillosis, mucormycosis, and
      tuberculosis and those of healthy volunteers. METHODS: Adult patients who were
      diagnosed with PCP, candidemia, CDC, invasive aspergillosis, mucormycosis, and
      tuberculosis whose blood samples were available, and healthy volunteers were
      enrolled in a tertiary hospital in Seoul, South Korea, during a 21-month period.
      The blood samples were assayed with the Goldstream Fungus (1-3)-beta-D-glucan
      test (Gold Mountain River Tech Development, Beijing, China). RESULTS: A total of
      136 individuals including 50 patients P. jirovecii,15 candidemia, 6 CDC, 15
      invasive aspergillosis, 10 mucormycosis, and 40 controls (20 TB and 20 healthy
      volunteers) were included. The mean+/-SD of the concentration of 1-3-beta-D
      glucan in the patients with PCP (290.08 pg/mL+/-199.98) were similar to those of
      patients with candidemia (314.14 pg/mL+/-205.60, p = 0.90 at an alpha = 0.005)
      and CDC (129.74 pg/mL+/-182.79, p = 0.03 at an alpha = 0.005), but higher than
      those of patients with invasive aspergillosis (131.62 pg/mL+/-161.67, p = 0.002
      at an alpha = 0.005), mucormycosis (95.08 pg/mL+/-146.80, p<0.001 at an alpha =
      0.005), and tuberculosis (103.31 pg/mL+/-140.81, p<0.001 at an alpha = 0.005) as
      well as healthy volunteers (101.18 pg/mL+/-197.52, p<0.001 at an alpha = 0.005).
      At a cut-off value > 31.25 pg/mL, which is highly sensitive for PCP versus
      tuberculosis plus healthy volunteers at the expense of specificity, the BG assay
      had a sensitivity of 92% (95% CI 81%-98%) and a specificity of 55% (95% CI 39%
      71%). CONCLUSIONS: The BG assay appears to be a useful adjunct test for PCP.

PMID- 29190811
TI  - Network dynamics of human face perception.
AB  - Prevailing theories suggests that cortical regions responsible for face
      perception operate in a serial, feed-forward fashion. Here, we utilize invasive
      human electrophysiology to evaluate serial models of face-processing via
      measurements of cortical activation, functional connectivity, and cortico
      cortical evoked potentials. We find that task-dependent changes in functional
      connectivity between face-selective regions in the inferior occipital (f-IOG) and
      fusiform gyrus (f-FG) are bidirectional, not feed-forward, and emerge following
      feed-forward input from early visual cortex (EVC) to both of these regions.
      Cortico-cortical evoked potentials similarly reveal independent signal
      propagations between EVC and both f-IOG and f-FG. These findings are incompatible
      with serial models, and support a parallel, distributed network underpinning face
      perception in humans.

PMID- 29190813
TI  - Flow cytometric discrimination of seven lineage markers by using two
      fluorochromes.
AB  - Flow cytometry is the primary immunological technique used to analyze multiple
      parameters on complex cell populations. We present a staining method that
      identifies major human mononuclear lymphoid and myeloid populations (CD4+ and
      CD8+ T cells, gammadelta T cells, B cells, NK cells and monocytes), using only
      two fluorochromes and a minimal number of cells. Our approach increases the
      number of markers recordable on most flow cytometers allowing for a deeper and
      more comprehensive immunophenotyping.

PMID- 29190814
TI  - Whole genome sequencing of Oryza sativa L. cv. Seeragasamba identifies a new
      fragrance allele in rice.
AB  - Fragrance of rice is an important trait that confers a large economic benefit to
      the farmers who cultivate aromatic rice varieties. Several aromatic rice
      varieties have limited geographic distribution, and are endowed with variety
      specific unique fragrances. BADH2 was identified as a fragrance gene in 2005, and
      it is essential to identify the fragrance alleles from diverse geographical
      locations and genetic backgrounds. Seeragasamba is a short-grain aromatic rice
      variety of the indica type, which is cultivated in a limited area in India. Whole
      genome sequencing of this variety identified a new badh2 allele (badh2-p) with an
      8 bp insertion in the promoter region of the BADH2 gene. When the whole genome
      sequences of 76 aromatic varieties in the 3000 rice genome project were analyzed,
      the badh2-p allele was present in 13 varieties (approximately 17%) of both indica
      and japonica types. In addition, the badh2-p allele was present in 17 varieties
      that already had the loss-of-function allele, badh2-E7. Taken together, the
      frequency of badh2-p allele (approximately 40%) was found to be greater than that
      of the badh2-E7 allele (approximately 34%) among the aromatic rice varieties.
      Therefore, it is suggested to include badh2-p as a predominant allele when
      screening for fragrance alleles in aromatic rice varieties.

PMID- 29190816
TI  - A national survey of clinical pharmacy services in county hospitals in China.
AB  - BACKGROUND: Clinical pharmacy is not only a medical science but also an elaborate
      public health care system firmly related to its subsystems of education,
      training, qualification authentication, scientific research, management, and
      human resources. China is a developing country with a tremendous need for
      improvements in the public health system, including the clinical pharmacy service
      system. OBJECTIVES: The aim of this research was to evaluate the infrastructure
      and personnel qualities of clinical pharmacy services in China. SETTING: Public
      county hospitals in China. MATERIALS AND METHOD: A national survey of clinical
      pharmacists in county hospitals was conducted. It was sampled through a
      stratified sampling strategy. Responses were analyzed using descriptive and
      inferential statistics. The main outcome measures include the coverage of
      clinical pharmacy services, the overall staffing of clinical pharmacists, the
      software and hardware of clinical pharmacy services, the charge mode of clinical
      pharmacy services, and the educational background, professional training
      acquisition, practical experience, and entry path of clinical pharmacists.
      RESULTS: The overall coverage of clinical pharmacy services on both the
      department scale (median = 18.25%) and the patient scale (median = 15.38%) does
      not meet the 100% coverage that is required by the government. In 57.73% of the
      sample hospitals, the staffing does not meet the requirement, and the size of the
      clinical pharmacist group is smaller in larger hospitals. In addition, 23.4% of
      the sample hospitals do not have management rules for the clinical pharmacists,
      and 43.1% do not have rational drug use software, both of which are required by
      the government. In terms of fees, 89.9% of the sample hospitals do not charge for
      the services. With regard to education, 8.5% of respondents are with unqualified
      degree, and among respondents with qualified degree, 37.31% are unqualified in
      the major; 43% of respondents lack the clinical pharmacist training required by
      the government. Most respondents (93.5%) have a primary or medium professional
      title. The median age and work seniority of respondents are 31 and four years,
      respectively. Only 18.5% of respondents chose this occupation by personal
      consideration or willingness. CONCLUSIONS: The main findings in this research
      include the overall low coverage of clinical pharmacy services, the low rate of
      clinical pharmacy service software, hardware, and personnel as well as a wide
      variance in educational training of pharmacists at county hospitals.

PMID- 29190815
TI  - Aldose reductase modulates acute activation of mesenchymal markers via the beta
      catenin pathway during cardiac ischemia-reperfusion.
AB  - Aldose reductase (AR: human, AKR1B1; mouse, AKR1B3), the first enzyme in the
      polyol pathway, plays a key role in mediating myocardial ischemia/reperfusion
      (I/R) injury. In earlier studies, using transgenic mice broadly expressing human
      AKR1B1 to human-relevant levels, mice devoid of Akr1b3, and pharmacological
      inhibitors of AR, we demonstrated that AR is an important component of myocardial
      I/R injury and that inhibition of this enzyme protects the heart from I/R injury.
      In this study, our objective was to investigate if AR modulates the beta-catenin
      pathway and consequent activation of mesenchymal markers during I/R in the heart.
      To test this premise, we used two different experimental models: in vivo, Akr1b3
      null mice and wild type C57BL/6 mice (WT) were exposed to acute occlusion of the
      left anterior descending coronary artery (LAD) followed by recovery for 48 hours
      or 28 days, and ex-vivo, WT and Akr1b3 null murine hearts were perfused using the
      Langendorff technique (LT) and subjected to 30 min of global (zero-flow) ischemia
      followed by 60 min of reperfusion. Our in vivo results reveal reduced infarct
      size and improved functional recovery at 48 hours in mice devoid of Akr1b3
      compared to WT mice. We demonstrate that the cardioprotection observed in Akr1b3
      null mice was linked to acute activation of the beta-catenin pathway and
      consequent activation of mesenchymal markers and genes linked to fibrotic
      remodeling. The increased activity of the beta-catenin pathway at 48 hours of
      recovery post-LAD was not observed at 28 days post-infarction, thus indicating
      that the observed increase in beta-catenin activity was transient in the mice
      hearts devoid of Akr1b3. In ex vivo studies, inhibition of beta-catenin blocked
      the cardioprotection observed in Akr1b3 null mice hearts. Taken together, these
      data indicate that AR suppresses acute activation of beta-catenin and, thereby,
      blocks consequent induction of mesenchymal markers during early reperfusion after
      myocardial ischemia. Inhibition of AR might provide a therapeutic opportunity to
      optimize cardiac remodeling after I/R injury.

PMID- 29190817
TI  - Screening for precancerous anal lesions with P16/Ki67 immunostaining in HIV
      infected MSM.
AB  - BACKGROUND: Screening of anal cancer in HIV-infected MSM with anal cytology
      results in high rates of false positive results and elevated burden of high
      resolution anoscopies. High-risk HPV up-regulates p16 and Ki67 expression in
      epithelial cells. We assessed the usefulness of P16/Ki-67 immunostaining cytology
      for the diagnosis of precancerous anal lesions. METHODOLOGY: Cross-sectional
      multicenter study. Concomitant anal liquid cytology with p16/Ki-67 immunostaining
      and HRA with biopsy of acetowhite lugol-negative lesions was performed in HIV
      infected MSM. We compared the diagnostic performance of an abnormal anal cytology
      and p16/Ki-67 immunostaining relative to HRA-guided biopsy by logistic regression
      and comparison of ROC areas. RESULTS: We included 328 HIV-infected MSM. HSIL was
      histologically diagnosed in 72 subjects (25.1%), and 2 (0.6%) were diagnosed with
      anal cancer. An abnormal cytology showed a sensitivity of 95.6% and a specificity
      of 58.8% for the diagnosis of biopsy-proven HSIL. P16/Ki67 positivity was
      associated with the presence of biopsy-proven HSIL (P trend = 0.004) but with low
      sensitivity (41.2%) and specificity (71%). The combination of standard cytology
      with P16/Ki67 immunostaining did not increment the predictive value of standard
      cytology alone (AUC 0.685 vs. 0.673, respectively, P = 0.688). CONCLUSION: In HIV
      infected MSM P16/Ki67 immunostaining does not improve the diagnostic accuracy of
      anal cytology, which shows a high sensitivity yet poor specificity. Other
      approaches aimed at improving the diagnostic accuracy of current techniques for
      the diagnostic of precancerous HSIL are warranted.

PMID- 29190818
TI  - Role of cis-trans proline isomerization in the function of pathogenic
      enterobacterial Periplasmic Binding Proteins.
AB  - Periplasmic Binding Proteins (PBPs) trap nutrients for their internalization into
      bacteria by ABC transporters. Ligand binding triggers PBP closure by bringing its
      two domains together like a Venus flytrap. The atomic determinants that control
      PBP opening and closure for nutrient capture and release are not known, although
      it is proposed that opening and ligand release occur while in contact with the
      ABC transporter for concurrent substrate translocation. In this paper we
      evaluated the effect of the isomerization of a conserved proline, located near
      the binding site, on the propensity of PBPs to open and close. ArgT/LAO from
      Salmonella typhimurium and HisJ from Escherichia coli were studied through
      molecular mechanics at two different temperatures: 300 and 323 K. Eight
      microseconds were simulated per protein to analyze protein opening and closure in
      the absence of the ABC transporter. We show that when the studied proline is in
      trans, closed empty LAO and HisJ can open. In contrast, with the proline in cis,
      opening transitions were much less frequent and characterized by smaller changes.
      The proline in trans also renders the open trap prone to close over a ligand. Our
      data suggest that the isomerization of this conserved proline modulates the PBP
      mechanism: the proline in trans allows the exploration of conformational space to
      produce trap opening and closure, while in cis it restricts PBP movement and
      could limit ligand release until in productive contact with the ABC transporter.
      This is the first time that a proline isomerization has been related to the
      control of a large conformational change like the PBP flytrap mechanism.

PMID- 29190819
TI  - The ectodomain of cadherin-11 binds to erbB2 and stimulates Akt phosphorylation
      to promote cranial neural crest cell migration.
AB  - During development, a multi-potent group of cells known as the cranial neural
      crest (CNC) migrate to form craniofacial structures. Proper migration of these
      cells requires proteolysis of cell adhesion molecules, such as cadherins. In
      Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC
      migration. However, overexpression of the soluble cleavage product (EC1-3) is
      capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC
      migration has not been investigated until now. Here we show that EC1-3 stimulates
      phosphorylation of Akt, a target of PI3K, in X.laevis CNC. Through
      immunoprecipitation experiments, we determined that EC1-3 interacts with all ErbB
      receptors, PDGFRalpha, and FGFR1. Of these receptors, only ErbB2 was able to
      produce an increase in Akt phosphorylation upon treatment with a recombinant EC1
      3. This increase was abrogated by mubritinib, an inhibitor of ErbB2. We were able
      to recapitulate this decrease in Akt phosphorylation in vivo by knocking down
      ErbB2 in CNC cells. Knockdown of the receptor also significantly reduced CNC
      migration in vivo. We confirmed the importance of ErbB2 and ErbB receptor
      signaling in CNC migration using mubritinib and canertinib, respectively.
      Mubritinib and the PI3K inhibitor LY294002 significantly decreased cell migration
      while canertinib nearly prevented it altogether. These data show that ErbB2 and
      Akt are important for CNC migration and implicate other ErbB receptors and Akt
      independent signaling pathways. Our findings provide the first example of a
      functional interaction between the extracellular domain of a type II classical
      cadherin and growth factor receptors.

PMID- 29190820
TI  - Interactive effects of spectral quality and trace metal availability on the
      growth of Trichodesmium and Symbiodinium.
AB  - Light and trace metals are critical growth factors for algae but how the
      interdependence of light quality and metal availability affects algal growth
      remains largely unknown. Our previous studies have demonstrated the importance of
      Ni and Fe on the growth of Trichodesmium and Symbiodinium, respectively, two
      important marine primary producers inhabiting environments with high light
      intensities. Here, we investigated the effects of light quality and intensity
      with availability of either Ni or Fe on their growth. For Trichodesmium, we found
      that specific growth rates for high Ni treatments were all significantly higher
      than in corresponding low Ni treatments with varying light quality and intensity.
      The inhibitory effect of low intensity red light was also countered by sufficient
      Ni supply. For Symbiodinium, we found that growth rates and biomass were reduced
      by 75% under low intensity red light and the stress can only be partially
      relieved by sufficient Fe supply. The results show that trace metal availability
      plays an important role in relieving the stress induced by low red light
      condition for both Trichodesmium and Symbiodinium although the cyanobacterium
      performs better in this growth condition. The difference may be attributed to the
      presence of phycocyanin, a unique pigment attuned to absorption of red light, in
      Trichodesmium. Our study shows that the concerted effects of light intensity and
      quality compounded with trace metal availability may influence the growth of
      photosynthetic organisms in the ocean.

PMID- 29190821
TI  - Overexpression of native ferritin gene MusaFer1 enhances iron content and
      oxidative stress tolerance in transgenic banana plants.
AB  - Iron is an indispensable element for plant growth and defense and hence it is
      essential to improve the plant's ability to accumulate iron. Besides, it is also
      an important aspect for human health. In view of this, we attempted to increase
      the iron content in banana cultivar Rasthali using MusaFer1 as a candidate gene.
      Initially, the expression of all five genes of the MusaFer family (MusaFer1-5)
      was quantified under iron-excess and -deficient conditions. The supplementation
      of 250 and 350 MUM iron enhanced expression of all MusaFer genes; however,
      MusaFer1 was increased maximally by 2- and 4- fold in leaves and roots
      respectively. Under iron deficient condition, all five MusaFer genes were
      downregulated, indicating their iron dependent regulation. In MusaFer1
      overexpressing lines, iron content was increased by 2- and 3-fold in leaves and
      roots respectively, as compared with that of untransformed lines. The increased
      iron was mainly localized in the epidermal regions of petiole. The analysis of
      MusaFer1 promoter indicated that it might control the expression of iron
      metabolism related genes and also other genes of MusaFer family. MusaFer1
      overexpression led to downregulated expression of MusaFer3, MusaFer4 and MusaFer5
      in transgenic leaves which might be associated with the plant's compensatory
      mechanism in response to iron flux. Other iron metabolism genes like Ferric
      reductase (FRO), transporters (IRT, VIT and YSL) and chelators (NAS, DMAS and
      NAAT) were also differentially expressed in transgenic leaf and root, suggesting
      the multifaceted impact of MusaFer1 towards iron uptake and organ distribution.
      Additionally, MusaFer1 overexpression increased plant tolerance against methyl
      viologen and excess iron which was quantified in terms of photosynthetic
      efficiency and malondialdehyde content. Thus, the study not only broadens our
      understanding about iron metabolism but also highlights MusaFer1 as a suitable
      candidate gene for iron fortification in banana.

PMID- 29190823
TI  - Correction: Cooling induces phase separation in membranes derived from isolated
      CNS myelin.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184881.].

PMID- 29190824
TI  - Comparison of laser and circumlimbal suture induced elevation of intraocular
      pressure in albino CD-1 mice.
AB  - Animal models of ocular hypertension are important tools for glaucoma studies.
      Both acute transient models and chronic models of ocular hypertension may be
      useful to investigate specific aspects of neurodegeneration. In this study, we
      compare the intraocular pressure (IOP) and inner retinal changes induced by 1)
      laser photocoagulation of both episcleral veins and limbal vessels and 2)
      circumlimbal suture in CD-1 mice. The suture group is divided into 3 subgroups
      depending on the level of the immediate IOP spike (acute > 55 mmHg or chronic <
      55 mmHg) and time period of monitoring (7 or 28 days). The laser group is
      followed for 7 days. IOP data show that it peaks at 5 hours and returns to normal
      level within 7 days in the laser group. In all suture groups, IOP spikes
      initially and decreases gradually, but it remains significantly elevated at 7
      days. In 7 days, the acute suture model generates rapid loss of retinal nerve
      fiber layer (RNFL) and retinal ganglion cells (RGCs) when compared to the gradual
      loss by the chronic suture model, possibly due to retinal ischemia and
      reperfusion within the first few hours after treatment. The laser model falls
      between the acute suture and chronic suture models resulting in less RNFL and RGC
      loss than the acute suture model but significantly more loss than the chronic
      suture model. These results suggest that when using suture models of IOP
      elevation, it is critical to take the initial IOP spike into consideration and to
      choose between the acute and chronic models depending on respective research
      purposes.

PMID- 29190822
TI  - The tumor suppressor phosphatase PP2A-B56alpha regulates stemness and promotes
      the initiation of malignancies in a novel murine model.
AB  - Protein phosphatase 2A (PP2A) is a ubiquitously expressed Serine-Threonine
      phosphatase mediating 30-50% of protein phosphatase activity. PP2A functions as a
      heterotrimeric complex, with the B subunits directing target specificity to
      regulate the activity of many key pathways that control cellular phenotypes. PP2A
      B56alpha has been shown to play a tumor suppressor role and to negatively control
      c-MYC stability and activity. Loss of B56alpha promotes cellular transformation,
      likely at least in part through its regulation of c-MYC. Here we report
      generation of a B56alpha hypomorph mouse with very low B56alpha expression that
      we used to study the physiologic activity of the PP2A-B56alpha phosphatase. The
      predominant phenotype we observed in mice with B56alpha deficiency in the whole
      body was spontaneous skin lesion formation with hyperproliferation of the
      epidermis, hair follicles and sebaceous glands. Increased levels of c-MYC
      phosphorylation on Serine62 and c-MYC activity were observed in the skin lesions
      of the B56alphahm/hm mice. B56alpha deficiency was found to increase the number
      of skin stem cells, and consistent with this, papilloma initiation was
      accelerated in a carcinogenesis model. Further analysis of additional tissues
      revealed increased inflammation in spleen, liver, lung, and intestinal lymph
      nodes as well as in the skin lesions, resembling elevated extramedullary
      hematopoiesis phenotypes in the B56alphahm/hm mice. We also observed an increase
      in the clonogenicity of bone marrow stem cells in B56alphahm/hm mice. Overall,
      this model suggests that B56alpha is important for stem cells to maintain
      homeostasis and that B56alpha loss leading to increased activity of important
      oncogenes, including c-MYC, can result in aberrant cell growth and increased stem
      cells that can contribute to the initiation of malignancy.

PMID- 29190825
TI  - Spillover of the Atlantic bluefin tuna offspring from cages in the Adriatic Sea:
      A multidisciplinary approach and assessment.
AB  - During routine monitoring of commercial purse seine catches in 2011, 87
      fingerling specimens of scombrids were collected in the southern Adriatic Sea.
      Sequencing of the mitochondrial DNA control region locus inferred that specimens
      belonged to the Atlantic bluefin tuna, Thunnus thynnus (Linnaeus, 1758) (N = 29),
      bullet tuna, Auxis rochei (Risso, 1810) (N = 30) and little tunny, Euthynnus
      alletteratus, Rafinesque, 1810 (N = 28). According to previously published growth
      parameters, the age of the collected specimens was estimated at approximately 30
      40 days, suggesting they might have been spawned in the Adriatic Sea, contrary to
      the current knowledge. A coupled modelling system with hydrodynamic (ROMS) and
      individual based model (IBM-Ichthyop) was set up to determine the location of the
      spawning event. Numerical simulations with the IBM model, both backward and
      forward in time, indicate commercial tuna cages in the middle Adriatic coastal
      area as possible spawning location. The two other non-commercial species likely
      opportunistically use the positive environmental (abiotic and biotic) conditions
      to spawn in the same area.

PMID- 29190826
TI  - Biological responses of the marine diatom Chaetoceros socialis to changing
      environmental conditions: A laboratory experiment.
AB  - Diatoms constitute a major group of phytoplankton, accounting for ~20% of the
      world's primary production. It has been shown that iron (Fe) can be the limiting
      factor for phytoplankton growth, in particular, in the HNLC (High Nutrient Low
      Chlorophyll) regions. Iron plays thus an essential role in governing the marine
      primary productivity and the efficiency of biological carbon pump. Oceanic
      systems are undergoing continuous modifications at varying rates and magnitudes
      as a result of changing climate. The objective of our research is to evaluate how
      changing environmental conditions (dust deposition, ocean warming and
      acidification) can affect marine Fe biogeochemistry and diatom growth. Laboratory
      culture experiments using a marine diatom Chaetoceros socialis were conducted at
      two temperatures (13 degrees C and 18 degrees C) and under two pCO2 (carbon
      dioxide partial pressure) (400 MUatm and 800 MUatm) conditions. The present study
      clearly highlights the effect of ocean acidification on enhancing the release of
      Fe upon dust deposition. Our results also confirm that being a potential source
      of Fe, dust provides in addition a readily utilizable source of macronutrients
      such as dissolved phosphate (PO4) and silicate (DSi). However, elevated
      atmospheric CO2 concentrations may also have an adverse impact on diatom growth,
      causing a decrease in cell size and possible further changes in phytoplankton
      composition. Meanwhile, ocean warming may lead to the reduction of diatom
      production and cell size, inducing poleward shifts in the biogeographic
      distribution of diatoms. The changing climate has thus a significant implication
      for ocean phytoplankton growth, cell size and primary productivity, phytoplankton
      distribution and community composition, and carbon (C), nitrogen (N), phosphorus
      (P), silicon (Si) and Fe biogeochemical cycles in various ways.

PMID- 29190828
TI  - Retraction: Exploration of inhibitory mechanisms of curcumin in lung cancer
      metastasis using a miRNA- transcription factor-target gene network.

PMID- 29190827
TI  - Intra-venous bevacizumab in hereditary hemorrhagic telangiectasia (HHT): A
      retrospective study of 46 patients.
AB  - BACKGROUND: Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged
      as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT).
      Its utilization in this orphan disease has rapidly spread despite the lack of
      randomized trials and international guidelines. The objective of this study is to
      report the main clinical data (baseline characteristics, dose schedule, efficacy,
      adverse events and deaths) of HHT patients treated by intravenous bevacizumab in
      France. METHODS: Retrospective observational study of HHT patients treated with
      bevacizumab for a severe form of the disease in the 14 centers of the French HHT
      network. RESULTS: Forty-six patients (median age: 68 years) were treated between
      March 2009 and May 2015. Ten patients were treated for high output cardiac
      failure, 20 patients for severe hemorrhages and 16 for both indications. The
      standard protocol (6 infusions of 5mg/kg every 2 weeks) was initially used in 89%
      of the cases but diverse strategies were subsequently applied. A clinical
      improvement was noted by the referent physician for 74% of the patients with a
      median effect's duration of 6 months. Wound healing complications led to 2
      amputations. Arthralgia/arthritis and arterial hypertension occurred in 5
      patients each. One third of the patients were dead at the time of the final
      update, coherently with age and the poor prognosis of these highly symptomatic
      patients. CONCLUSION: Intravenous bevacizumab seems to provide a clinical
      benefice in severe HHT patients. Precautions concerning wound healing and
      vascular pathologies must be respected. Prospective double blinded versus placebo
      trials are needed.

PMID- 29190829
TI  - A comprehensive analysis of breast cancer microbiota and host gene expression.
AB  - The inflammatory tumoral-immune response alters the physiology of the tumor
      microenvironment, which may attenuate genomic instability. In addition to
      inducing inflammatory immune responses, several pathogenic bacteria produce
      genotoxins. However the extent of microbial contribution to the tumor
      microenvironment biology remains unknown. We utilized The Cancer Genome Atlas,
      (TCGA) breast cancer data to perform a novel experiment utilizing unmapped and
      mapped RNA sequencing read evidence to minimize laboratory costs and effort. Our
      objective was to characterize the microbiota and associate the microbiota with
      the tumor expression profiles, for 668 breast tumor tissues and 72 non-cancerous
      adjacent tissues. The prominent presence of Proteobacteria was increased in the
      tumor tissues and conversely Actinobacteria abundance increase in non-cancerous
      adjacent tissues. Further, geneset enrichment suggests Listeria spp to be
      associated with the expression profiles of genes involved with epithelial to
      mesenchymal transitions. Moreover, evidence suggests H. influenza may reside in
      the surrounding stromal material and was significantly associated with the
      proliferative pathways: G2M checkpoint, E2F transcription factors, and mitotic
      spindle assembly. In summary, further unraveling this complicated interplay
      should enable us to better diagnose and treat breast cancer patients.

PMID- 29190831
TI  - Erectile dysfunction and quality of life in men receiving methadone or
      buprenorphine maintenance treatment. A cross-sectional multicentre study.
AB  - BACKGROUND: Erectile dysfunction (ED) is common among men on opioid replacement
      therapy (ORT), but most previous studies exploring its prevalence and
      determinants yielded contrasting findings. Moreover, the impact of ED on
      patients' quality of life (QoL) has been seldom explored. OBJECTIVE: To explore
      the prevalence and determinants of ED in men on ORT, and the impact on QoL.
      METHODS: In a multicentre cross-sectional study, we recruited 797 consecutive
      male patients on methadone and buprenorphine treatment, collected data on
      demographic, clinical, and psychopathological factors, and explored their role as
      predictors of ED and QoL through univariate and multivariate analysis. ED
      severity was assessed with a self-assessment questionnaire. RESULTS: Nearly half
      of patients in our sample were sexually inactive or reported some degree of ED.
      Some demographic, clinical and psychopathological variables significantly
      differed according to the presence or absence of ED. Multivariate regression
      analysis indicated that age, employment, smoke, psychoactive drugs, opioid
      maintenance dosage, and severity of psychopathological factors significantly
      influenced the risk and severity of ED. QoL was worse in patients with ED and
      significantly correlated with ED severity. Age, education, employment, opioid
      maintenance dosage, ED score, and severity of psychopathology significantly
      influenced QoL in the multivariate analysis. CONCLUSIONS: ED complaints can be
      explored in male opioid users on ORT through a simple and quick self-assessment
      tool. ED may have important effects on emotional and social well-being, and may
      affect outcome.

PMID- 29190830
TI  - Reduced functional connectivity of fronto-parietal sustained attention networks
      in severe childhood abuse.
AB  - Childhood maltreatment is associated with attention deficits. We examined the
      effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA, FKBP5) interaction
      on functional brain connectivity during sustained attention in medication/drug
      free adolescents. Functional connectivity was compared, using generalised
      psychophysiological interaction (gPPI) analysis of functional magnetic resonance
      imaging (fMRI) data, between 21 age-and gender-matched adolescents exposed to
      severe childhood abuse and 27 healthy controls, while they performed a
      parametrically modulated vigilance task requiring target detection with a
      progressively increasing load of sustained attention. Behaviourally, participants
      exposed to childhood abuse had increased omission errors compared to healthy
      controls. During the most challenging attention condition abused participants
      relative to controls exhibited reduced connectivity, with a left-hemispheric
      bias, in typical fronto-parietal attention networks, including dorsolateral,
      rostromedial and inferior prefrontal and inferior parietal regions. Abuse-related
      connectivity abnormalities were exacerbated in individuals homozygous for the
      risky C-allele of the single nucleotide polymorphism rs3800373 of the FK506
      Binding Protein 5 (FKBP5) gene. Findings suggest that childhood abuse is
      associated with decreased functional connectivity in fronto-parietal attention
      networks and that the FKBP5 genotype moderates neurobiological vulnerability to
      abuse. These findings represent a first step towards the delineation of abuse
      related neurofunctional connectivity abnormalities, which hopefully will
      facilitate the development of specific treatment strategies for victims of
      childhood maltreatment.

PMID- 29190832
TI  - Low level of polyandry constrains phenotypic plasticity of male body size in
      mites.
AB  - Polyandry, i.e. females mating with multiple males, is more common than
      previously anticipated and potentially provides both direct and indirect fitness
      benefits to females. The level of polyandry (defined by the lifetime number of
      male mates of a female) is an important determinant of the occurrence and
      intensity of sexual selection acting on male phenotypes. While the forces of
      sexual selection acting on phenotypic male traits such as body size are
      relatively well understood, sexual selection acting on phenotypic plasticity of
      these traits is unexplored. We tackled this issue by scrutinizing the link
      between polyandry and phenotypic plasticity of male body size in two sympatric
      plant-inhabiting predatory mite species, Phytoseiulus persimilis and Neoseiulus
      californicus. These two species are similar in life history, ecological niche
      requirements, mating behavior, polygyny and female body size plasticity but
      strikingly differ in the level of both polyandry and phenotypic plasticity of
      male body size (both lower in P. persimilis). We hypothesized that deviations
      from standard body size, i.e. the size achieved under favorable conditions, incur
      higher costs for males in the less polyandrous P. persimilis. To test our
      hypotheses, we conducted two experiments on (i) the effects of male body size on
      spermatophore transfer in singly mating females and (ii) the effects of mate
      sequence (switching the order of standard-sized and small males) on mating
      behavior and paternity success in doubly mating females. In P. persimilis but not
      N. californicus, small males transferred fewer but larger spermatophores to the
      females; in both species, females re-mated more likely with standard-sized
      following small than small following standard-sized males; in P. persimilis,
      first standard-sized males sired a higher proportion of offspring produced after
      re-mating by the female than first small males, whereas in N. californicus the
      paternity success of small and standard-sized males was independent of the mating
      sequence. Based on our results and pertinent previous studies, which showed that
      females of P. persimilis, but not N. californicus, prefer mating with standard
      sized over small males and allow them fertilizing more eggs, the lack of
      interspecific difference in female body size plasticity, and the absence of any
      clue pointing at a role of natural selection, we suggest that the interspecific
      difference in male body size plasticity is sexually selected. Our study provides
      an indication of sexual selection constraining plasticity of male phenotypes,
      suggesting that the level of polyandry may be an important co-determinant of the
      level of phenotypic plasticity of male body size.

PMID- 29190833
TI  - Lupus nephritis progression in FcgammaRIIB-/-yaa mice is associated with early
      development of glomerular electron dense deposits and loss of renal DNase I in
      severe disease.
AB  - FcgammaRIIB-/-yaa mice develop severe lupus glomerulonephritis due to lack of an
      inhibitory immune cell receptor combined with a Y-chromosome linked autoimmune
      accelerator mutation. In the present study, we have investigated nephritis
      development and progression in FcgammaRIIB-/-yaa mice to find shared features
      with NZB/NZW F1 lupus prone mice and human disease. We sacrificed 25 male
      FcgammaRIIB-/-yaa mice at various disease stages, and grouped them according to
      activity and chronicity indices for lupus nephritis. Glomerular morphology and
      localization of electron dense deposits containing IgG were further determined by
      immune electron microscopy. Renal DNase I and pro-inflammatory cytokine mRNA
      levels were measured by real-time quantitative PCR. DNase I protein levels was
      assessed by immunohistochemistry and zymography. Our results demonstrate early
      development of electron dense deposits containing IgG in FcgammaRIIB-/-yaa mice,
      before detectable levels of serum anti-dsDNA antibodies. Similar to NZB/NZW F1,
      electron dense deposits in FcgammaRIIB-/-yaa progressed from being confined to
      the mesangium in the early stage of lupus nephritis to be present also in
      capillary glomerular basement membranes. In the advanced stage of lupus
      nephritis, renal DNase I was lost on both transcriptional and protein levels,
      which has previously been shown in NZB/NZW F1 mice and in human disease. Although
      lupus nephritis appears on different genetic backgrounds, our findings suggest
      similar processes when comparing different murine models and human lupus
      nephritis.

PMID- 29190834
TI  - Ephrin-B2 reverse signaling regulates progression and lymph node metastasis of
      oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and
      neck and frequently metastasizes to cervical lymph nodes. Aggressive local
      invasion and metastasis of OSCC are significant factors for poor prognosis. In
      this study, we investigated whether ephrin-B2 expressed in OSCC contributed to
      tumor progression and lymph node metastasis. Clinical specimens from patients
      with OSCC had robust ephrin-B2-positive tumor cells and ephrin-B2 protein level
      was associated with clinical stage, lymph node metastasis, and poor survival
      outcomes. We also determined that ephrin-B2 protein level was increased in OSCC
      cell lines compared to normal human oral keratinocytes and that its levels were
      associated with the migratory and invasive potential of OSCC cell lines.
      Transfection of an EFNB2-specific small interfering RNA (siRNA) into SAS-L1 cells
      significantly reduced proliferation, attachment, migration, and invasion through
      phosphorylation of the epidermal growth factor receptor, FAK, ERK1/2, p38, AKT,
      and JNK1/2 pathways. Furthermore, knockdown of EFNB2 significantly suppressed
      adhesion and transmigration of SAS-L1 cells toward human lymphatic endothelial
      cells. In addition, the growth rate of tumor xenografts and cervical lymph node
      metastases of OSCC were suppressed by local injection of EFNB2 siRNA. These
      results suggest that ephrin-B2 overexpression and activation of the ephrin-B2
      reverse signaling pathway in tumor microenvironment in OSCC facilitates
      progression and lymph node metastasis via enhancement of malignant potential and
      interaction with surrounding cells.

PMID- 29190835
TI  - When the doctor is crazier than the patient.
AB  - [Full article available at http://rimed.org/rimedicaljournal-2017-12.asp].

PMID- 29190836
TI  - Addressing patient biases toward physicians.
AB  - [Full article available at http://rimed.org/rimedicaljournal-2017-12.asp].

PMID- 29190837
TI  - Menstrual hygiene plight of homeless women, a public health disgrace.
AB  - [Full article available at http://rimed.org/rimedicaljournal-2017-12.asp].

PMID- 29190838
TI  - Slipping through the cracks: A cross-sectional study examining older adult
      emergency department patient fall history, post-fall treatment and prevention.
AB  - Falls are the leading cause of emergency department (ED) visits for fatal and non
      fatal injuries among adults 65 years old and older. We aimed to better understand
      the fall history, risk for further falls, and actions taken to prevent further
      falls among this higher fall risk population. This cross-sectional study included
      older adults without cognitive impairment presenting to the Rhode Island Hospital
      ED from February to May 2017. Of the 76 participants, 35 self-reported no prior
      falls, and 41 self-reported at least one prior fall, of whom 20 fell on the day
      of ED presentation. Participants with vs. without self-reported prior falls were
      similar in age, gender, race, and substance use. Participants with prior falls
      scored lower on cognitive testing and had more comorbidities associated with
      falls. Only one quarter of those with prior falls reported making changes and few
      were evaluated by professionals to prevent future falls. This study highlights
      that older adult ED patients who sustain a fall are at higher risk for subsequent
      falls, and that greater fall prevention efforts are needed to protect this
      vulnerable group. [Full article available at http://rimed.org/rimedicaljournal
      2017-12.asp].

PMID- 29190839
TI  - Violence Against Women: Injuries and Deaths in Rhode Island Yongwen Jiang, PhD;
      Deborah Debare, MMHS; Lynne-Marie Shea, BA; Samara Viner-Brown, MS.
AB  - Violence against women is a public health issue. Monitoring assault-related
      injury and homicide death among women is imperative for understanding this public
      health issue. We used data from the 2014 Rhode Island emergency department (ED),
      hospital discharge (HD), and 2004-2014 Rhode Island violent death reporting
      system (RIVDRS) to provide a broad picture for violence against women injuries
      and deaths in Rhode Island. ED visit and HD data show that the majority of female
      assault injuries occurred among women aged 25-44, resided in the core cities, and
      had public insurance. RIVDRS data showed that over half of the homicides among
      women were aged 25-64; nearly two in five were non-Hispanic black or Hispanic.
      Precipitating circumstances include intimate partner violence, a preceding
      argument or a conflict, and precipitated by another crime. Evidence-informed
      interventions need to target high-risk populations and urban areas to effectively
      reduce violence against women. [Full article available at
      http://rimed.org/rimedicaljournal-2017-12.asp].

PMID- 29190840
TI  - A Woman with a Necrotizing Soft-Tissue Infection.
AB  - [Full article available at http://rimed.org/rimedicaljournal-2017-12.asp].

PMID- 29190841
TI  - The Physical Finding Points to the Diagnosis.
AB  - [Full article available at http://rimed.org/rimedicaljournal-2017-12.asp].

PMID- 29190842
TI  - Health profile of Rhode Island healthcare workers.
AB  - [Full article available at http://rimed.org/rimedicaljournal-2017-12.asp].

PMID- 29190843
TI  - Practicing Medicine in 1917 Rhode Island.
AB  - Using editorials published in the Rhode Island Medical Journal's inaugural year,
      this article examines what it meant to practice medicine in Rhode Island in 1917.
      One hundred years ago, the state's medical community was undergoing rapid
      transformation epitomized by a turn toward the germ theory of disease, ongoing
      education and hospital reform, and a growing sense of the profession's political
      and social role. In many ways, the social and professional concerns of Rhode
      Island physicians in 1917 continue to resonate today. Physicians writing in the
      Journal were excited by but concerned about technological advancement in
      medicine, debating how new institutions and sites of care would shape their
      interactions with patients. They were also influenced by broader social changes
      affecting the medical profession, expressing ambivalence toward regulation,
      debating the implications of social insurance and compulsory health insurance,
      and reflecting on their financial livelihood and the social prestige of their
      profession. [Full article available at http://rimed.org/rimedicaljournal-2017
      12.asp].

PMID- 29190844
TI  - Uterocervical Angle Measurement Improves Prediction of Preterm Birth in Twin
      Gestation.
AB  - OBJECTIVE:  Twin pregnancies are associated with an increased risk of spontaneous
      preterm birth. Our objective was to compare the performance of uterocervical
      angle to cervical length as predictors of spontaneous preterm birth in this
      population. METHODS:  We conducted a retrospective cohort study of twin
      gestations at a single center from May 2008 to 2016 who received a transvaginal
      ultrasound for the evaluation of the cervix between 16 0/7 and 23 0/7 weeks. The
      primary outcome was prediction of preterm birth <28 and <32 weeks by
      uterocervical angle and cervical length. RESULTS:  Among 259 women with twin
      gestation, the mean gestational age at birth was 34.83 +/- 3.48 weeks. Receiver
      operator characteristic curves demonstrated optimal prediction of spontaneous
      preterm birth prior to 32 weeks at a uterocervical angle >110 degrees  (80%
      sensitivity, 82% specificity) [odds ratio (OR), 15.7 (95% confidence interval
      (CI), 7.2-34.4)] versus cervical length <20 mm (53% sensitivity, 85% specificity;
      p < 0.001, OR, 6.4 [95% CI, 2.3-17.8]) and similarly, prior to 28 weeks at a
      uterocervical angle >114 degrees  (OR, 24.3 [95% CI, 6.7-88.5]) compared with
      cervical length <20 mm (OR, 11.4 [95% CI, 3.5-36.7]). CONCLUSION:  Uterocervical
      angles >110 degrees  performed better than cervical length for the prediction of
      spontaneous preterm birth in twin gestations.

PMID- 29190845
TI  - Nasogastric Feeding Tubes May Not Contribute to Gastroesophageal Reflux in
      Preterm Infants.
AB  - OBJECTIVE:  The objective was to determine if the presence of a nasogastric (NG)
      feeding tube is associated with increased gastroesophageal reflux (GER) and acid
      exposure in preterm infants. STUDY DESIGN:  This is a retrospective study on
      preterm infants [gestational age (GA) <37 weeks] who were evaluated by
      multichannel intraluminal impedance and pH monitoring (MII-pH) between October
      2009 and March 2016. Infants were divided into two groups, NG tube present and no
      feeding tube. GER events per hour and the percent of time with pH <4 during a 24
      hour period were then compared. RESULTS:  Eighty-three infants were included, 41
      had an NG tube present and 42 did not. The group without an NG tube had
      significantly more reflux events per hour (2.3 +/- 2.9 vs. 1.3 +/- 0.8, p < 0.05)
      even after adjusting for differences in birth weight, GA, corrected GA, and total
      fluid intake. There was no significant difference in acidic events per hour and
      acid exposure time between the two groups. CONCLUSION:  The presence of a 5
      French NG tube is not associated with an increase in GER or acid exposure in
      preterm infants. In fact, it appears that infants fed through an NG tube have
      fewer episodes of GER.

PMID- 29190846
TI  - Characterization of Thermal and Mechanical Indices from Serial Ultrasound Exams
      and Associations with Neonatal Anthropometry: The NICHD Fetal Growth Studies.
AB  - OBJECTIVE:  This article aims to determine if the number of maternal ultrasound
      scans where the highest thermal (TI) or mechanical (MI) indices recorded during
      obstetrical ultrasound exceed 1.0 were associated with neonatal anthropometric
      measurements. STUDY DESIGN:  A prospective cohort of 2,334 nonobese low-risk
      pregnant women from 12 U.S. clinical sites underwent a total of six ultrasound
      scans, for which the highest TI and MI values were recorded. Neonatal
      anthropometric measurements were obtained within 12 to 24 hours of delivery.
      Multiple linear regression models adjusted for maternal race/ethnicity, body mass
      index, weight gain, and gestational age were used to examine associations between
      the number of maternal ultrasounds during gestation with a TI or MI exceeding 1.0
      and the mean change in neonatal anthropometry. RESULTS:  Ultrasounds with TI or
      MI >1.0 were not associated with birth weight, neonatal length, nor head, chest,
      and abdominal circumferences. TI >1.0 was negatively associated with neonatal mid
      upper arm and mid-upper thigh circumferences. MI >1.0 was negatively associated
      with neonatal skinfold measurements of the anterior thigh and triceps, and
      neonatal circumferences of the mid-upper thigh and umbilicus. CONCLUSION: 
      Prenatal ultrasound examinations in which TI or MI intermittently exceeded 1.0
      did not identify a pattern of alterations of birth size.

PMID- 29190848
TI  - Temporal Relationship of Onset of Necrotizing Enterocolitis and Introduction of
      Enteric Feedings and Powdered Milk Fortifier.
AB  - OBJECTIVE:  This article evaluates temporal relationships between onset of
      necrotizing enterocolitis (NEC) in preterm infants and introduction of enteral
      feedings or powdered human milk fortifier (HMF). STUDY DESIGN:  This is a Poisson
      regression analysis of NEC cases at a single children's hospital between 1999 and
      2009, using the self-controlled case series method to estimate adjusted daily
      event rate ratios (DERR) during postexposure intervals. RESULTS:  Of 139 patients
      with a clinical diagnosis of NEC, 26 had early disease onset prior to initiation
      of feeding and were considered to be cases of spontaneous intestinal perforation
      (SIP). For the remaining 113 infants, the DERR for NEC onset were significantly
      greater on days for which infants were <14 days of age (DERR, 2.15; 95%
      confidence interval [CI], 1.22-3.79) or >=31 weeks postmenstrual age (2.94; 95%
      CI, 1.51-5.83) or which fell within 14 days after initiation of enteric feeding
      (8.29; 95% CI, 4.73-14.53) or 4 days after introduction of HMF (12.32; 95% CI,
      7.13-21.29). CONCLUSION:  There are strong temporal associations between onset of
      NEC and initiation of enteral feeding or powdered HMF in preterm infants.

PMID- 29190847
TI  - Adverse Maternal and Neonatal Outcomes in Indicated Compared with Spontaneous
      Preterm Birth in Healthy Nulliparas: A Secondary Analysis of a Randomized Trial.
AB  - OBJECTIVE:  To compare the risks of adverse maternal and neonatal outcomes
      associated with spontaneous (SPTB) versus indicated preterm births (IPTB).
      METHODS:  A secondary analysis of a multicenter trial of vitamin C and E
      supplementation in healthy low-risk nulliparous women. Outcomes were compared
      between women with SPTB (due to spontaneous membrane rupture or labor) and those
      with IPTB (due to medical or obstetric complications). A primary maternal
      composite outcome included: death, pulmonary edema, blood transfusion, adult
      respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular
      necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal
      composite outcome included: neonatal death, RDS, grades III or IV
      intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or
      retinopathy of prematurity. RESULTS:  Of 9,867 women, 10.4% (N = 1,038) were
      PTBs; 32.7% (n = 340) IPTBs and 67.3% (n = 698) SPTBs. Compared with SPTB, the
      composite maternal outcome was more frequent in IPTB-4.4% versus 0.9% (adjusted
      odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.8), as were blood
      transfusion and prolonged hospital stay (3.2 and 3.7 times, respectively). The
      frequency of composite neonatal outcome was higher in IPTBs (aOR, 1.8; 95% CI,
      1.1-3.0), as were RDS (1.7 times), small for gestational age (SGA) < 5th
      percentile (7.9 times), and neonatal intensive care unit (NICU) admission (1.8
      times). CONCLUSION:  Adverse maternal and neonatal outcomes were significantly
      more likely with IPTB than with SPTB.

PMID- 29190849
TI  - Concussion Recovery Phase Affects Vestibular and Oculomotor Symptom Provocation.
AB  - Vestibular and oculomotor testing is emerging as a valuable assessment in sport
      related concussion (SRC). However, their usefulness for tracking recovery and
      guiding return-to-play decisions remains unclear. Therefore the purpose of this
      study was to evaluate their clinical usefulness for tracking SRC recovery.
      Vestibular and oculomotor assessments were used to measure symptom provocation in
      an acute group (n=21) concussed<=10 days, prolonged symptoms group (n=10)
      concussed >=16 days (median=84 days), healthy group (n=58) no concussions in >6
      months. Known-groups approach was used with three groups at three time points
      (initial, 2-week and 6-week follow-up). Provoked symptoms for Gaze-Stabilization
      (GST), Rapid Eye Horizontal (REH), Optokinetic Stimulation (OKS), Smooth-Pursuit
      Slow (SPS) and Fast (SPF) tests, total combined symptoms scores and near point
      convergence (NPC) distance were significantly greater at initial assessment in
      both injury groups compared to controls. Injury groups improved on the King
      Devick test and combined symptom provocation scores across time. The acute group
      improved over time on REH and SPF tests, while the prolonged symptoms group
      improved on OKS. A regression model (REH, OKS, GST) was 90% accurate
      discriminating concussed from healthy. Vestibular and ocular motor tests give
      valuable insight during recovery. They can prove beneficial in concussion
      evaluation given the modest equipment, training and time requirements. The
      current study demonstrates that when combined, vestibular and oculomotor clinical
      tests aid in the detection of deficits following a SRC. Additionally, tests such
      as NPC, GST, REH, SPS, SPF OKS and KD provide valuable information to clinicians
      throughout the recovery process and may aid in return to play decisions.

PMID- 29190850
TI  - MRI Cartilage Assessment of the Subtalar and Midtarsal Joints During a
      Transcontinental Ultramarathon - New Insights into Human Locomotion.
AB  - MR measurements can be accurately performed during 4486 km of running, opening a
      window into in vivo assessment of hindfoot articular cartilage under extreme
      ultra-endurance loading. This observational cross-sectional study included 22
      randomized participants of TransEurope FootRace between Italy and the North Cape,
      which was accompanied by a trailer-mounted 1.5T MRI scanner over 9 weeks. Four
      follow up MR examinations of subtalar and midtarsal joints were performed.
      Statistics of cartilage T2*  and thickness were obtained. Nearly all observed
      joints showed an initial significant mean T2*  increase of 20.9% and 26.3% for
      the left and right side, followed by a relative decrease of 28.5% and 16.0%
      during the second half, respectively. It could be demonstrated that mobile MRI
      field studies allow in vivo functional tissue observations under extreme loading.
      Elevated T2*  values recovered during the second half of the ultramarathon
      supported the evidence that this response is a physiological adaptive mechanism
      of chondrocyte function via upregulation of de novo synthesis of proteoglycans
      and collagen. These changes occurred in a distinct asymmetric pattern leaving a
      "biochemical signature" of articular cartilage that allows in vivo insight into
      joint loading. In conclusion, the normal articular cartilage of the hindfoot is
      resilient and adaptive, leaving extreme endurance activities up to limitless
      human ambition.

PMID- 29190851
TI  - Oxidized Low-Density Lipoprotein and Cell Adhesion Molecules Following Exercise
      Training.
AB  - Elevated oxidized low-density lipoprotein (ox-LDL) and cell adhesion molecules
      are associated with inflammation and atherosclerosis. The role of exercise in
      circulating ox-LDL, enzyme mediators, and cell adhesion molecules are not clearly
      understood in obesity. As a randomized controlled design, 27 obese (BMI>30 kg/m2)
      sedentary men (N=13) and women (N=14) were randomly assigned to either an
      exercise (N=15) or a control (N=12) group. The exercise group performed a 60-min
      supervised treadmill exercise at moderate intensity (70% of HRmax) for 3 days per
      week for 4 weeks, while the control group did not exercise. Overnight fasting
      blood samples were collected before and after the study period to analyze serum
      lipids, lipoprotein-cholesterol, ox-LDL, 12- and 15-lipoxygenases,
      myeloperoxidase (MPO), and soluble vascular cell adhesion molecules-1 and
      intercellular adhesion molecule-1. Moderate-intensity exercise training lowered
      both ox-LDL (from 44.76+/-1.99 to 38.51+/-1.99 U/L, p=0.032) and MPO (from
      31.48+/-2.20 to 23.09+/-2.20 ng/mL, p=0.010), without significantly altering body
      weight, other parameters of serum lipids and lipoproteins, or soluble cell
      adhesion molecules. Moderate intensity exercise training reduced the levels of ox
      LDL and MPO, indicating a reduced risk for developing CVD and additional
      protection to the possible metabolic complications associated with obesity.

PMID- 29190852
TI  - Exercise Prescription Using the Borg Rating of Perceived Exertion to Improve
      Fitness.
AB  - The present study aimed to compare two fitness-training methodologies,
      instability circuit resistance training (ICRT) versus traditional circuit
      resistance training (TCRT), applying an experimental model of exercise
      prescription controlling and modulating exercise load using the Borg rating of
      perceived exertion. Forty-four healthy young adults age (21.6+/-2.3 years) were
      randomly assigned to three groups: TCRT (n=14), ICRT (n=14) and a control group
      (n=16). Strength and cardiorespiratory tests were chosen to evaluate
      cardiorespiratory and muscular fitness before and after the training program. In
      cardiorespiratory data, a significant difference was observed for the time effect
      in VO2max, peak heart rate, peak velocity, and heart rate at anaerobic threshold
      intensity (p<0.05) in the experimental groups. In strength variables, a
      significant Group x Time interaction effect was detected in 1RM, in mean
      propulsive power, and in peak power (p<=0.01) in the back squat exercise. In the
      bench press exercise, a significant time effect was detected in 1RM, in mean
      propulsive power, and in peak power, and a Group x Time interaction in peak power
      (all p<0.05). We can conclude that applying an experimental model of exercise
      prescription using RPE improved cardiorespiratory and muscular fitness in healthy
      young adults in both experimental groups.

PMID- 29190853
TI  - Contributions of Hamstring Stiffness to Straight-Leg-Raise and Sit-and-Reach Test
      Scores.
AB  - The passive straight-leg-raise (PSLR) and the sit-and-reach (SR) tests have been
      widely used to assess hamstring extensibility. However, it remains unclear to
      what extent hamstring stiffness (a measure of material properties) contributes to
      PSLR and SR test scores. Therefore, we aimed to clarify the relationship between
      hamstring stiffness and PSLR and SR scores using ultrasound shear wave
      elastography. Ninety-eight healthy subjects completed the study. Each subject
      completed PSLR testing, and classic and modified SR testing of the right leg.
      Muscle shear modulus of the biceps femoris, semitendinosus, and semimembranosus
      was quantified as an index of muscle stiffness. The relationships between shear
      modulus of each muscle and PSLR or SR scores were calculated using Pearson's
      product-moment correlation coefficients. Shear modulus of the semitendinosus and
      semimembranosus showed negative correlations with the two PSLR and two SR scores
      (absolute r value<=0.484). Shear modulus of the biceps femoris was significantly
      correlated with the PSLR score determined by the examiner and the modified SR
      score (absolute r value<=0.308). The present findings suggest that PSLR and SR
      test scores are strongly influenced by factors other than hamstring stiffness and
      therefore might not accurately evaluate hamstring stiffness.

PMID- 29190854
TI  - [Clostridium difficile Infection: Epidemiology, Clinical Presentation, Therapy
      and Prevention].
AB  - Clostridium difficile infections (CDI) are common causes of diarrhoea in
      hospitalised medical and surgical patients. Clinical presentation ranges from
      mild diarrhoea to pseudomembraneous enterocolitis of the colon and sometimes the
      small intestines, with development of a toxic megacolon. Recurrent infections are
      common. Early diagnosis is necessary because of high rates of complications and
      mortality. Knowledge of risk factors for the development of CDI is recommended.
      Early initiation of therapy is recommended to avoid complications and standard
      therapy is antibiotics, while therapy with monoclonal antibodies and vaccination
      is under research and development. Fulminant septic courses indicate surgical
      source control. Minimally invasive surgical therapy establishing a loop ileostomy
      and antibiotic installation via enema has to be considered as early surgical
      intervention. Fecal microbiotic transplantation is a new therapeutic option for
      recurrent infection. Provisions for prevention and control have to be established
      to avoid in-hospital spread of pathogenic agents. This includes isolation of
      patients, personalisation of instruments, restriction of in-hospital transports,
      protective clothing and gloves, strict hand washing and antibiotic stewardship
      (ABS).

PMID- 29190856
TI  - Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo.
AB  - We created a novel paclitaxel (PTX) nanoparticle drug delivery system and
      compared this to acommercial injection preparation to evaluate the antitumor
      effects for both formulations in vivo and in vitro.PTXnanocrystals were 194.9 nm
      with potential of -29.6 mV. Cytotoxicity tests indicated that both formulations
      had similar effects and cytotoxicity was dose- and time
      dependent.Pharmacodynamics indicated that the drug concentration at the tumor was
      greater with PTX nanocrystals compared to commercial injection (P<0.01) and that
      drug accumulated more and for a longer duration. In vivo antitumor evaluation
      indicated significant antitumor effects and low toxicity of PTX nanocrystals.
      Moreover, bioimaging indicated that the PTX retention time in MCF-7-bearing mice
      was longer, especially at the tumor site, and this high drug concentration was
      maintained for a long time.Overall, PTX nanocrystalsare feasible and superior to
      traditional injection formulation chemotherapy.

PMID- 29190855
TI  - Efficacy of Lophira alata Leaf Extract and its Combination with Artesunate in
      Mice Prior Exposed to Plasmodium berghei.
AB  - Enhanced antimalarial activity of plant extracts used for treatment of malaria in
      endemic areas is attributed to partial immunity gained by prior infection. This
      suggests synergy between immunity and extract activity in treatment. Testing this
      hypothesis, rodent malaria was used to determine efficacy of Lophira alata leaf
      extracts in treating malaria in prior infected mice. One round of P. berghei
      infection and Pyrimethamine drug-cure was used to establish partial immunity in
      mice. Previously Exposed Mice (PEM) and Previously Unexposed Mice (PUM) mice
      challenged with P. berghei were used to determine influence of partial
      antimalarial immunity on efficacy of L. alata leaf extracts, administered alone
      or in combination with Artesunate (ART) in malaria treatment. There was a
      significant reduction in parasitemia in PEM when compared to PUM animals
      (P<0.001) irrespective of treatment regimen. Administration of L. alata combined
      with ART significantly reduced parasitemia (P<0.0032) and prolonged (P=0.0109)
      survival than when L. alata was administered alone in infected mice. These
      findings suggest that the action of L. alata in treating malaria infections in a
      murine model is enhanced by prior exposure to the malaria parasite. Thus the
      requirements of using plants in treating malaria in endemic populations may
      differ for those used in western systems, where trials are carried out with non
      immune cohorts. Combining artemisinin derivatives and medicinal plants in malaria
      exposed populations may provide an alternative control measure in endemic regions
      and may justify the continued use of these plants by indigenous populations in
      treating malaria.

PMID- 29190857
TI  - Preparation, in vitro Characterization and Pharmacokinetic Study of Coenzyme Q10
      Long-Circulating Liposomes.
AB  - Long-circulating liposomal delivery systems of encapsulated Coenzyme Q10 (CoQ10),
      a ubiquinone anti-cataract agent, were developed with different molar ratios of
      PEGylated lipids and/or cholesterol. The resulting samples were contrasted
      through observation of morphology, analysis of particle size and Zeta potential,
      and in vivo pharmacokinetics. A protamine aggregation method with high
      selectivity was developed to determine the encapsulation efficiency (EE), after
      which the liposome formulation was further optimized by applying a Box Behnken
      design (BBD) using EE as the evaluation index. The results showed that liposomes
      had a large, unilamellar structure, and that particle sizes of cholesterol
      containing liposomes increased along with the increase of cholesterol molar
      percentage, while the size of PEGylated vesicles decreased slightly as PEG-lipid
      contents increasing. The optimum formulation and optimal values of each
      influencing factor were quantitatively obtained, and the measured value was
      highly consistent with the predicted results. In vivo evaluation performed by
      liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)
      demonstrated that liposomal encapsulation largely prolonged half-lives and
      improved bioavailability for vectors prepared with either lipid component, and
      the liposomes composed of both cholesterol and PEG-lipid possessed the best
      pharmacokinetic properties. The results suggest that incorporating high contents
      of cholesterol and PEG modification could be a potentially useful method for
      enhancing the length of circulation and the sustained release effect for liposome
      encapsulated chemicals.

PMID- 29190858
TI  - [The Revista Medica del IMSS in the 2017 Healthcare Book Fair].
AB  - On August, the second edition of the Healthcare Book Fair took place, sponsored
      by the Facultad de Medicina of UNAM. Again, the Revista Medica del Instituto
      Mexicano del Seguro Social participated with a stand where we promoted it, talked
      about the different indexes where our journal is included, explained its
      objective and scope, and finally talked about its nature as an open access
      journal, which is aimed to the clinical staff of the different health
      institutions of our country.

PMID- 29190860
TI  - [Hemodynamic regime of asymptomatic heart disease patients studied by
      echocardiogram].
AB  - BACKGROUND: Viewing heart failure as a clinical syndrome delays treatment and
      impairs prognosis, which leads to the question: Is it possible to make an early
      diagnosis based on echocardiography studies? METHODS: It was carried out a review
      of medical records of asymptomatic heart disease patients, with no treatment, who
      were studied by echocardiogram in order to measure cardiac output (CO) and total
      peripheral vascular resistance (TPVR), for which mean blood pressure was
      calculated. It is described the hemodynamic regime on the basis of the proportion
      of three integrated groups according to CO and TPVR. RESULTS: The hemodynamic
      regime in 200 heart disease patients was hypokinetic in 36%, hyperkinetic in 17%
      and eukinetic in 47%. CONCLUSIONS: Non-invasive hemodynamic study identified
      asymptomatic heart failure in one third of the cases.

PMID- 29190859
TI  - [Work accidents associated with the discouragement of SERUMS physicians to work
      in the primary care services of Lima, Peru].
AB  - BACKGROUND: Employee retention is an important issue, because professionals are
      required in primary care services (PCS). The objective was to determine whether
      accidents were associated with the discouragement of physicians to work in PCS in
      Lima, Peru. METHODS: Analytical cross-sectional study of secondary data from a
      database generated from a survey of physicians who performed his Rural and Urban
      Health Care Service (Servicio Rural y Urbano-Marginal en Salud: SERUMS). We only
      included physicians who said at the beginning of their SERUMS that they could
      work in PCS in Lima. Those who completed their service and reported that they no
      longer wished to work in Lima were defined as change of intention to work in PCS.
      This was associated with having a work accident and was adjusted with other
      variables. RESULTS: Out of 124 physicians, 63% (78) were men. Median age was 26
      years (interquartile range: 25-27 years). After they completed their SERUMS, 12%
      (15) said they changed their mind and that they wished to work in Lima. In the
      multivariate analysis, having had an accident diminished the frequency of
      changing their mind of working in the PCS (aPR: 0.28, 95% CI: 0.14-0.54, p <
      0.001), adjusted for eight variables. CONCLUSIONS: A previous study found that
      work accidents decreased the frequency outside Lima, but our study states the
      opposite, probably because of the perception that a job in the capital would
      allow them to be closer to services; to be cared for in case of any emergency.

PMID- 29190861
TI  - [Prediction of acute kidney injury in critically ill patients treated with
      intermittent hemodialysis versus CRRT].
AB  - BACKGROUND: Acute kidney injury (AKI) is common in critically ill patients and it
      is associated with poor outcome. Some patients require renal replacement therapy
      (RRT), and the most frequently used are intermittent hemodialysis (IHD) and
      continuous renal replacement therapies (CRRT). Current evidence is insufficient
      to conclude which modality is most appropriate to treat critically ill patients
      with AKI. METHODS: We reviewed the clinical records of critically ill patients
      with stage 3 AKI treated with RRT. We recorded demographic and clinical data and
      serum creatinine. We compared the evolution and prognosis of patients treated
      with IHD versus those treated with CRRT by Student's t test, chi squared, Kaplan
      Meier curves, and Cox regression. Logistic regression was performed to determine
      the association between RRT and mortality. RESULTS: We analyzed 221 patients; the
      mean age was 49.8 years, and 55.2% were men. Mortality was 36.7%. IHD was used in
      73.8% and CRRT in 26.2% of cases. In the group treated with CRRT, the severity of
      disease was higher, the recovery of renal function less frequent, the need for
      long-term RRT less frequent, and mortality higher, compared with those treated
      with IHD. CRRTs had an odds ratio (OR) of 8.64 for mortality (p = 0.063).
      CONCLUSIONS: IHD is the RRT most frequently used. Mortality is higher in patients
      treated with CRRT. CRRTs are not an independent risk factor for death.

PMID- 29190862
TI  - [Comparison of mortality by femur fracture versus hip fracture in elderly
      patients in a period of five years].
AB  - BACKGROUND: Fractures in the elderly population are an economic, social and
      medical challenge. Not much is known about fractures in this population, which
      makes difficult the selection of an appropriate treatment. Hip fractures (HF)
      increase the risk of death and morbidity. Patients with midshaft femur fracture
      (MFF) have less morbidity and risk of death. The objective was to compare HF and
      MFF's survival. METHODS: Observational analytic study. The Hospital General de
      Mexico database was used to gather patients aged 65 to 94 years with HF and MFF
      from 2010 to 2014. Patients had an heterogeneous follow-up and their cognitive
      status was not considered; we had a total of 146 patients. Follow-up was made
      through phone call. RESULTS: Kaplan-Meier estimate was used to assess survival.
      We compared survival depending on type of fracture and found no statistically
      significant difference (p = 0.97). On sub-analysis, we compared type of fracture
      on male gender (p = 0.21) and female gender (p = 0.316) and found no
      statistically significant difference on survival. This differs from what has been
      reported. It was used t test to evaluate survival in months, according to male
      (39.61 +/- 19.1) and female (36.58 +/- 23.19) gender; this showed a significant
      difference in both groups (p = 0.037). CONCLUSIONS: In the presence of fractures,
      we must consider gender when estimating survival on patients with hip or midshaft
      femur fracture.

PMID- 29190863
TI  - [Effect of exercise on the serum concentrations of leptin and adiponectin in
      adolescents with risk factors of developing diabetes].
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is an increasing health issue.
      Physical activity (PA) in early stages is a preventive measure in the development
      of degenerative diseases. It has been documented the association between exercise
      and leptin and adiponectin concentrations. The objective was to evaluate the
      effect of a physical activity program (PAP) on serum leptin and adiponectin in
      teenagers with risk factors for developing T2DM. METHODS: Experimental
      longitudinal study. Teenagers (men and women), with T2DM risk factors, aged 14 to
      16 years, participated in a PAP for three months, five days a week, 45 minutes
      each day. Before and after the program, all anthropometric variables, incluiding
      leptin and adiponectin, were evaluated. RESULTS: 22 adolescents participated in
      the PAP and they were compared with 22 adolescents from the control group (who
      did not participate in the PAP). There was a reduction in the serum concentration
      of leptin in the intervention group (baseline 23 +/- 13; after the PAP 14 +/- 8,
      p > 0.0001), compared with the control group (baseline 18 +/- 13, three months
      follow-up 20 +/- 14, p < 0.520). Also, the adiponectin concentration increased
      (baseline 10 +/- 3, after the PAP 13 +/- 4.0, p > 0.014), compared with the
      control group (baseline 11 +/- 3, 13 +/- 4.0 after the PAP p > 0.032).
      CONCLUSIONS: This study support the efficacy of an aerobic exercise intervention
      on metabolic markers of adolescents with risk factors for developing diabetes.

PMID- 29190864
TI  - [Application of BARS scale in children with ataxia in a child rehabilitation
      center in Chiapas, Mexico].
AB  - BACKGROUND: Ataxias are an heterogeneous group of diseases with different
      etiologies. Scales are used to understand better its natural history and evaluate
      properly drug efficacy in clinical trials. SARA and ICARS scales have been the
      most studied and validated so far. BARS scale is based on a modified form of the
      ICARS scale and is valid, reliable and sufficiently fast for clinical purposes.
      METHODS: Cross-sectional, descriptive and correlational study. Kruskall-Wallis
      test was used. We administered BARS to children from 4 to 18 years of age, with
      ataxic syndrome, without cognitive impairment, in active status, from February,
      2007 to September, 2014, at the CRIT (Centro de Rehabilitacion Infantil Teleton)
      from Chiapas, Mexico. RESULTS: 14 children were included. The main BARS score was
      17.9/30; 4H syndrome with the worst score was 27.6/30; ataxia telangiectasia
      15.6/30; ataxic cerebral palsy 12/30; and others 16.1/30. Kruskall-Wallis test
      did not show a significant statistically difference when comparing the etiology
      with BARS score (p = 0.068). CONCLUSIONS: BARS items were an easy way to assess
      ataxic clinic in children; worse condition was found in neurodegenerative ataxias
      and better results in ataxic cerebral palsy.

PMID- 29190865
TI  - [C677T-SNP of methylenetetrahydrofolate reductase gene and breast cancer in
      Mexican women].
AB  - BACKGROUND: Low-penetrance susceptibility genes such as 5,10
      methylenetetrahydrofolate reductase gene (MTHFR) have been considered in the
      progression of breast cancer (BC). Cancer is a result of genetic, environmental
      and epigenetic interactions; therefore, these genes should be studied in
      environmental context, because the results can vary between populations and even
      within the same country. The objective was to analyze the allelic and genotypic
      frequencies of the MTHFR C667T SNP in Mexican Mestizo patients with BC and
      controls from Northeastern Mexico. METHODS: 243 patients and 118 healthy women
      were studied. The analysis of the polymorphism was performed with a DNA
      microarray. Once the frequency of the polymorphism was obtained, Hardy-Weinberg
      equilibrium test was carried out for the genotypes. Chi square test was used to
      compare the distribution of frequencies. RESULTS: The allele frequency in
      patients was: C = 0.5406; T = 0.4594 and in controls C = 0.5678, T = 0.4322.
      Genotype in BC patients was: C / C = 29.9%, C / T = 48.3% and T / T = 21.8. The
      distribution in controls was: C / C = 31.4%, C / T = 50.8%, T / T = 17.8% (chi
      squared 0.77, p = 0.6801). CONCLUSIONS: Northeastern Mexican women in this study
      showed no association between MTFHR C667T SNP and the risk of BC. It seems that
      the contribution of this polymorphism to BC in Mexico varies depending on various
      factors, both genetic and environmental.

PMID- 29190866
TI  - [Chronic kidney disease in Mexico and its relation with heavy metals].
AB  - Chronic kidney disease (CKD) is a public health problem in Mexico, causing 25% of
      deaths related to diabetes mellitus (DM) and 28% related to hypertensive heart
      disease. In 2008 CKD reached the highest incidence of end-stage renal disease in
      the world. Diabetes mellitus is the main risk factor associated with CKD in
      Mexican population; however, heavy metals such as lead, arsenic, cadmium and
      mercury have been associated to nephropathies. In Mexico there are still high
      levels of these compounds in occupational and environmental settings; therefore,
      chronic exposures to these metals persist. In this review we approach to the main
      mechanisms of action of these metals in the body and its renal effects, as well
      as information about the sources of exposure to these chemical risks, the
      relationship between exposure to heavy metals and CKD, coupled with the economic
      and social consequences of this disease.

PMID- 29190867
TI  - [Breaking bad news in the emergency room: Suggestions and future challenges].
AB  - The aim of this paper is to describe educational programs that reportedly teach
      how to break bad news in the emergency department. We also suggest some
      recommendations on how to communicate bad news based on the research of evidence
      available in the field. The examined evidence points toward six major components
      with which physicians should familiarize when communicating bad news: 1) doctor
      patient empathic communication, 2) establishing a proper space to give the news,
      3) identifying characteristics of the person who receives the news, 4) essential
      aspects for communicating the news; 5) emotional support, and 6) medical and
      administrative aspects of the encounter. Finally, we point out several
      limitations in the studies in the field and future challenges identified in the
      communication of bad news in emergency room facilities.

PMID- 29190868
TI  - [Epidemiology and human rights: Zika virus outlook and reproductive rights in
      Latin America].
AB  - With this article we review the current Zika virus (ZIKV) epidemic. We also look
      back over the last scientific evidence relating ZIKV to microcephaly and Guillain
      Barre syndrome. Finally, we also address the challenges in terms of reproductive
      rights in Latin America.

PMID- 29190869
TI  - [Comment to the article "Double pneumothorax secondary to single projectile of
      firearm: report of a case and review of the literature].
AB  - No abstract.

PMID- 29190870
TI  - [Recommendations for the use of ranibizumab in diabetic macular edema at IMSS].
AB  - Diabetic macular edema can occur at any stage of diabetic retinopathy. It
      represents the main cause of vision loss in diabetes type I and II with a
      prevalence of 3-10% in diabetic patients of the Instituto Mexicano del Seguro
      Social (IMSS). Our aim is to elaborate treatment guidelines and provide
      recommendations for the use of intravitreal ranibizumab for diabetic medical
      edema at IMSS. Nine retina specialists and 10 ophthalmologists from IMSS high
      specialty medical units gathered to discuss the bibliographic evidence for the
      safety and efficacy of ranibizumab for this disease, in order to create consensus
      on its use in the institution. Intravitreal ranibizumab injection should be used
      on patients presenting diffuse or cystic diabetic macular edema who have strict
      metabolic control and visual acuity between 20/30 and 20/200 ETDRS, as well as
      structural features, such as inferior foveal limit of 280 MUm and ischemic areas
      no larger than 50% of the central foveal area. Treatment regime should consist of
      a loading charge of three monthly injections of ranibizumab 0.5 mg, followed by
      monthly follow-ups and treatment as needed according to anatomic and functional
      criteria. This consensus decision-making process on the criteria to treat and re
      treat patients with this drug will result in better health outcomes than those
      currently observed among patients with diabetic macular edema at IMSS.

PMID- 29190871
TI  - [Fifty years of services of biomedical information in health documentation
      centers in Puebla, Mexico].
AB  - Librarian and information services focused on supporting research, teaching, and
      health care are vital for the generation of new knowledge and its application in
      health care, both by staff and students, helps to improve the quality of medical
      care. Therefore, in this article we expose an historical and social tour of 50
      years of the Instituto Mexicano del Seguro Social's library services in Puebla.
      From 1964 to 2014 occurred many events in the development of these services in
      our area, from the creation of a small space in the basement, to the
      implementation of spaces created deliberately to provide dignified service to all
      users, which is why this historical sketch is here as an acknowledgement to the
      first librarians who contributed to the training of specialists in Mexico.

PMID- 29190872
TI  - [Level of teaching competence at the Undergraduate Medical Internship of UNAM's
      Faculty of Medicine].
AB  - BACKGROUND: There is no systematic evaluation of teaching performance in the
      clinical area at UNAM Faculty of Medicine. The study purpose is to assess the
      teaching competence level in the Undergraduate Medical Internship (UMI). METHODS:
      The paper describes the process of psychometric validity for the instrument
      designed to evaluate teaching competence in the UMI. This instrument was
      constructed from two previously developed instruments. The final version with 54
      items in a Likert scale was studied with exploratory factorial analysis. Four
      dimensions were obtained: Solution of clinical problems, Psychopedagogy,
      Mentoring, and Evaluation. The instrument had a reliability of 0.994, with an
      explained variance of 77.75%. RESULTS: To evaluate the teaching competence level,
      we administered 844 questionnaires to a sample of students with a response rate
      of 89%. We obtained an overall global score of 89.4 +/- 9.6 (mean +/- SD). The
      dimension Solution of clinical problems was the one with a greater value, in
      contrast with the dimension of Evaluation, which had a lower score. CONCLUSION:
      The teachers of the UMI are considered educators with high level of teaching
      competence, according to the perceptions of the undergraduate internal doctors.
      The evaluation of teaching competence level is very important for institutions
      that look for the continuous professional development of its faculty.

PMID- 29190873
TI  - [Segmental portal hypertension with splenic vein thrombosis caused by
      pancreatitis].
AB  - BACKGROUND: Splenic vein thrombosis is a complication of pancreatic carcinoma,
      pancreatitis or pancreatic pseudocyst. It may lead to segmental portal
      hypertension and bleeding from gastric varices. CLINICAL CASE: A 31 year-old man
      was diagnosed with pancreatitis of two weeks of evolution and was referred to our
      hospital in 2013. He had a history of alcohol consumption. Physical examination
      showed no stigmata of liver cirrhosis. Laboratory analyses revealed hemoglobin
      9.5 g/dL, and leukocytes and platelets were normal. Liver function tests were
      normal as well. Abdominal CT showed a pseudocyst, which was drained by
      percutaneous puncture. By pseudocyst recurrence, drainage and necrosectomy by
      retroperitoneal laparascopy were performed. The patient presented hyperglycemia
      during his treatment in hospital. He was discharged, but he returned to emergency
      room because of gastrointestinal bleeding without hemodynamic instability.
      Gastroscopy showed bleeding gastric varices. The colonoscopy showed normal
      results. Liver biopsy was also normal. Abdominal CT angiography revealed blockage
      of the splenic vein. Patient underwent splenectomy and was discharged.
      CONCLUSION: This case is rare due to the high frequency of portal hypertension
      and cirrhosis. The isolated gastric varices with normal liver function are a sign
      of splenic thrombosis. The definitive treatment is splenectomy.

PMID- 29190874
TI  - [Subaortic membrane in adults. A brief review of literature apropos of one case].
AB  - A 54-year-old man, ex smoker with high blood pressure and a history of possible
      Wolff-Parkinson-White syndrome was admitted for presenting an episode suggestive
      of acute coronary syndrome with immediate syncope and left bundle branch block,
      while performing physical activity. Angioplasty and a drug-eluting stent were
      performed in the left circumflex artery. Subsequently, Doppler echocardiography
      disclosed an image suggestive of a subaortic membrane. Given these findings, the
      patient underwent a 3D transesophageal echocardiogram and a magnetic resonance
      study, which confirmed the diagnosis of a subaortic membrane. In turn, in the
      Holter monitoring a paroxysmal pattern of Wolff-ParkinsonWhite was observed. The
      patient presented three possible causes of syncope. A stress echocardiogram
      elicited a gradient of 126 mm Hg, which could be possibly related to the syncopal
      episode that the patient suffered.

PMID- 29190875
TI  - [IgG4-related disease: a case report].
AB  - IgG4-related disease is an inflammatory condition characterized by high levels of
      IgG4. It affects salivary and lacrimal glands, pancreas, lymph nodes, lungs or
      kidney. The diagnosis is based on identifying a histological pattern with a dense
      lymphocyte and plasmacyte infiltration, focal fibrosis or phlebitis, finding more
      than 10 IgG4 positive cells per high power field and/or IgG4/IgG ratio in plasma
      higher than 40%. We present a patient with Mikulicz's disease who meets
      histological findings required for the diagnosis of IgG4 related disease.

PMID- 29190876
TI  - [Use of transmandibular approach for resection of a relapse pleomorphic adenoma
      on the parapharyngeal space].
AB  - In this review of a clinical case we study the most frequent benign neoplasia of
      the main salivary glands. We present the case of a four-year relapse of a patient
      post-operated of a conservative total parotidectomy. We expose different opinions
      about this neoplasia, and the clinical case of a 50-year old female patient that
      presents a relapse to the parapharyngeal space, for which we used a trans
      mandibular approach.

PMID- 29190877
TI  - Measurement of retropubic tissue thickness using intrapartum transperineal
      ultrasound to assess cephalopelvic disproportion.
AB  - PURPOSE: First, to describe a new method of assessing cephalopelvic disproportion
      by measuring the retropubic tissue thickness (RTT), and second, to determine
      whether RTT was associated with an eventual delivery by cesarean section.
      METHODS: Three-dimensional transperineal ultrasound scans were performed on 129
      laboring nulliparous women to obtain 3-dimensional volume datasets for assessing
      RTT. RTT was measured off-line by three operators (A, B, and C) as the shortest
      distance between the capsule of the pubic symphysis and the outer border of the
      fetal skull. The intraoperator repeatability of operator A and the interoperator
      reproducibility among A, B, and C were determined. The RTT in women who were
      delivered by cesarean section due to failure to progress was compared to that of
      women who had a vaginal delivery. RESULTS: The intraoperator repeatability for
      RTT was 1.2 mm. The overall RTT interoperator interclass correlation was 0.97
      (0.95-0.98). The RTT in women who had a spontaneous, instrumental, or cesarean
      delivery was 1.16+/-0.32 cm, 1.12+/-0.25 cm, and 0.94+/-0.25 cm, respectively.
      Women who were delivered by cesarean section had a significantly smaller RTT than
      women who had a spontaneous delivery (P=0.008). There was no statistically
      significant difference in RTT between patients who had a normal vaginal delivery
      and patients who had an instrumental delivery (P=0.990), or between those who had
      an instrumental delivery and those who had a cesarean delivery after the
      Bonferroni correction (P=0.120). CONCLUSION: RTT can be measured with
      satisfactory intraoperator repeatability and interoperator reproducibility. RTT
      was significantly smaller in women who eventually had a cesarean delivery than in
      those who had a vaginal delivery.

PMID- 29190878
TI  - STAMP2 is required for human adipose-derived stem cell differentiation and
      adipocyte-facilitated prostate cancer growth in vivo.
AB  - Six Transmembrane Protein of Prostate 2 (STAMP2) has been implicated in both
      prostate cancer (PCa) and metabolic disease. STAMP2 has unique anti-inflammatory
      and pro-metabolic properties in mouse adipose tissue, but there is limited
      information on its role in human metabolic tissues. Using human adipose-derived
      stem cells (ASCs), we report that STAMP2 expression is dramatically upregulated
      during adipogenesis. shRNA-mediated STAMP2 knockdown in ASCs significantly
      suppresses adipogenesis and interferes with optimal expression of adipogenic
      genes and adipocyte metabolic function. Furthermore, ASC-derived adipocyte
      mediated stimulation of prostate tumor growth in nude mice is significantly
      reduced upon STAMP2 knockdown in ASC adipocytes. These results suggest that
      STAMP2 is crucial for normal ASC conversion into adipocytes and their metabolic
      function, as well as their ability to facilitate PCa growth in vivo.

PMID- 29190879
TI  - Longevity of protective immune responses induced by a split influenza A (H7N9)
      vaccine mixed with MF59 adjuvant in BALB/c mice.
AB  - The influenza virus is a serious threat to public health worldwide. A novel avian
      influenza A (H7N9) virus with a mortality rate of approximately 30% has been
      identified as an unusually dangerous virus for humans by the World Health
      Organization. Pathogenic H7N9 continue to represent a public health concern, and
      several candidate vaccines are currently in development. We generated candidate
      H7N9 vaccine strains using reverse genetics, consisting of hemagglutinin and
      neuraminidase genes derived from a human H7N9 virus and the remaining genes from
      the PR8 (A/PuertoRico/8/34 (H1N1)) virus. This H7N9 vaccine exhibited superior
      efficacy when combined with MF59 compared to other adjuvants. Immunized BALB/c
      mice were followed to determine the duration of the protective immune response.
      Antibody levels decreased to between one-half and one-eighth of the peak values
      four months after the final dose of the vaccine. Previously vaccinated mice
      received an A/Zhejiang/DTID-ZJU01/2013 H7N9 challenge six months post
      vaccination, and all remained protected. We also verified that MF59 enhanced the
      HI, MN, and IgG antibody titers to influenza antigens. The humoral immune
      response and Th2 cytokine production following influenza challenge was potently
      induced in the animals that received the split vaccine. Therefore, the split H7N9
      influenza vaccine with the MF59 adjuvant could effectively induce antibody
      production and protect mice from H7N9 virus challenge even after six months.

PMID- 29190880
TI  - Enhancement of the anti-tumor activity of FGFR1 inhibition in squamous cell lung
      cancer by targeting downstream signaling involved in glucose metabolism.
AB  - Fibroblast Growth Factor Receptor (FGFR) signaling is a complex pathway which
      controls several processes, including cell proliferation, survival, migration,
      and metabolism. FGFR1 signaling is frequently deregulated via amplification/over
      expression in NSCLC of squamous histotype (SQCLC), however its inhibition has not
      been successfully translated in clinical setting. We determined whether targeting
      downstream signaling implicated in FGFR1 effects on glucose metabolism
      potentiates the anti-tumor activity of FGFR1 inhibition in SQCLC. In FGFR1
      amplified/over-expressing SQCLC cell lines, FGF2-mediated stimulation of FGFR1
      under serum-deprivation activated both MAPK and AKT/mTOR pathways and increased
      glucose uptake, glycolysis, and lactate production, through AKT/mTOR-dependent
      HIF-1alpha accumulation and up-regulation of GLUT-1 glucose transporter. These
      effects were hindered by PD173074 and NVP-BGJ398, selective FGFR inhibitors, as
      well as by dovitinib, a multi-kinase inhibitor. Glucose metabolism was hampered
      by the FGFR inhibitors also under hypoxic conditions, with consequent inhibition
      of cell proliferation and viability. In presence of serum, glucose metabolism was
      impaired only in cell models in which FGFR1 inhibition was associated with
      AKT/mTOR down-regulation. When the activation of the AKT/mTOR pathway persisted
      despite FGFR1 down-regulation, the efficacy of NVP-BGJ398 could be significantly
      improved by the combination with NVP-BEZ235 or other inhibitors of this signaling
      cascade, both in vitro and in xenotransplanted nude mice. Collectively our
      results indicate that inhibition of FGFR1 signaling impacts on cancer cell growth
      also by affecting glucose energy metabolism. In addition, this study strongly
      suggests that the therapeutic efficacy of FGFR1 targeting molecules in SQCLC may
      be implemented by combined treatments tackling on glucose metabolism.

PMID- 29190881
TI  - Toll-like receptor expression in human non-small cell lung carcinoma: potential
      prognostic indicators of disease.
AB  - Introduction: Lung cancer remains the highest cause of cancer mortality
      worldwide. Toll-like receptors (TLR) are innate immune receptors that have both
      pro- and anti-tumorigenic properties. Based on findings from epidemiological
      studies and in rodents, we hypothesized that elevated TLR expression would be a
      positive prognostic indicator of disease in non-small cell lung carcinoma
      patients. Results: Higher mRNA expression of TLR1-3 and 5-8 were significantly
      associated with increased overall survival (OS) when analyzed individually or as
      a group in both non-small cell lung carcinoma (NSCLC) patients and in the
      adenocarcinoma (ADC) subtype. Significant co-expression of many TLR combinations
      in ADC patients were also observed via RNA sequencing. Immunostaining
      demonstrated TLR4 and 8 significantly correlated in tumor tissue, similar to RNA.
      Methods: We used kmplot.com to perform a meta-analysis on mRNA expression of TLR1
      10 to determine any significant associations with OS in NSCLC and the ADC
      subtype. cBioportal was also used simultaneously to assess co-expression in TLR1
      10 in ADC patients via RNA sequencing and to identify any molecular alterations.
      Lastly, immunostaining for a subset of TLRs was conducted on ADC patients.
      Conclusions: Expression of innate immune receptors TLR1-10 is associated with
      improved survival outcomes in NSCLC. Thus, further evaluation of their predictive
      capacity and therapeutic utility is warranted.

PMID- 29190882
TI  - Functional polymorphisms in pre-miR146a and pre-miR499 are associated with
      systemic lupus erythematosus but not with rheumatoid arthritis or Graves' disease
      in Mexican patients.
AB  - Recently, different microRNA (miRNA) gene polymorphisms have been evaluated in
      patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and
      Graves' disease (GD). In the present study, we examined three single-nucleotide
      polymorphisms (SNPs) located in the pre-miR-146a (rs2910164G/C), pre-miR-196a-2
      (rs11614913C/T), and pre-miR-499 (rs3746444A/G) genes. Our study population
      included 900 Mexican patients with RA, SLE, or GD, as well as 486 healthy control
      individuals with no family history of inflammatory or autoimmune diseases.
      Genotyping was performed using TaqMan probes and a 5' exonuclease assay. None of
      the investigated SNPs were associated with RA or GD susceptibility under any
      genetic model (co-dominant, recessive, or dominant). Genotype and allele
      frequencies of the miR-196a-2 rs11614913C/T polymorphism were similar between SLE
      cases and controls. In contrast, the miR-146a rs2910164G/C and miR-499
      rs3746444A/G polymorphisms were associated with SLE susceptibility. These SNPs
      were not associated with lupus nephritis (LN). Our results suggest that
      polymorphisms in miR-146a, miR-196a-2, and miR-499 are not associated with RA or
      GD susceptibility. This is the first report documenting that the miR-146a
      rs2910164G/C and miR-499 rs3746444 polymorphisms are associated with SLE
      susceptibility but not with LN.

PMID- 29190883
TI  - Ghrelin protects against nucleus pulposus degeneration through inhibition of NF
      kappaB signaling pathway and activation of Akt signaling pathway.
AB  - The objective of the present study was to examine the potential role of ghrelin
      in degeneration of nucleus pulposus (NP). Lower expression levels of ghrelin were
      found in human NP cells stimulated with interleukin-1beta (IL-1beta). Moreover,
      exogenous ghrelin suppressed IL-1beta induced degeneration and inflammation
      associated biomarkers in human NP cells, including matrix metalloproteinase-13, a
      disintegrin and metalloproteinase with thrombospondin motifs-5, tumor necrosis
      factor-alpha and iNOS, which was possibly mediated by antagonization of NF-kappaB
      signaling. Moreover, ghrelin enhanced production of critical extracellular matrix
      of NP cells, including collagen 2, aggrecan, and Sox-9 in NP cells. Ghrelin also
      promoted NP tissue regeneration in a rabbit IVD degeneration model, which seems
      to be associated with growth hormone secretagogue receptor. Additionally, the
      protective role of ghrelin in anabolism potentially relies on activation of Akt
      signaling pathway. Taken together, ghrelin may represent a molecular target for
      prevention and treatment of intervertebral disc degeneration.

PMID- 29190884
TI  - The autophagy marker LC3 strongly predicts immediate mortality after surgical
      resection for hepatocellular carcinoma.
AB  - The remnant liver's ability to regenerate may affect post-hepatectomy immediate
      mortality. The promotion of autophagy post-hepatectomy could enhance liver
      regeneration and reduce mortality. This study aimed to identify predictive
      factors of immediate mortality after surgical resection for hepatocellular
      carcinoma (HCC). A total of 535 consecutive HCC patients who had undergone their
      first surgical resection in Taiwan were enrolled between 2010 and 2014.
      Clinicopathological data and immediate mortality, defined as all cause-mortality
      within three months after surgery, were analyzed. The expression of autophagy
      proteins (LC3, Beclin-1, and p62) in adjacent non-tumor tissues was scored by
      immunohistochemical staining. Approximately 5% of patients had immediate
      mortality after surgery. The absence of LC3, hypoalbuminemia (<3.5 g/dl), high
      alanine aminotransferase, and major liver surgery were significantly associated
      with immediate mortality in univariate analyses. Multivariate logistic regression
      demonstrated that absence of LC3 (hazard ratio/95% confidence interval: 40.8/5.14
      325) and hypoalbuminemia (2.88/1.11-7.52) were significantly associated with
      immediate mortality. The 3-month cumulative incidence of mortality was 12.1%,
      13.0%, 21.4% and 0.4%, respectively, among patients with absence of LC3
      expression, hypoalbuminemia, both, or neither of the two. In conclusion, the
      absence of LC3 expression in adjacent non-tumor tissues and hypoalbuminemia were
      strongly predictive of immediate mortality after resection for HCC.

PMID- 29190886
TI  - Metformin activates type I interferon signaling against HCV via activation of
      adenosine monophosphate-activated protein kinase.
AB  - Activation of the type I interferon (IFN) signaling pathway is essential for the
      eradication of hepatitis C virus (HCV). Metformin can activate adenosine
      monophosphate-activated protein kinase (AMPK) to reduce insulin resistance. Cross
      talks between AMPK and IFN signaling remain unclear. To understand the influence
      of metformin on the type I IFN signaling pathway and HCV infection, the full
      length HCV replicon OR6 cells and the infectious HCV clones JFH1 were used to
      assess the anti-HCV effect of the insulin sensitizers, metformin and
      pioglitazone. Immunofluorescence staining and the immunoblotting of HCV viral
      protein demonstrated that metformin, but not pioglitazone, inhibited HCV
      replication in OR-6 and JFH-1-infected Huh 7.5.1 cells. Immunoblotting data
      showed that metformin activated the phosphorylation of STAT-1 and STAT-2 in OR-6
      and JFH-1 infected Huh 7.5.1 cells. Metformin enhanced the phosphorylation of
      AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK
      inhibitor. After treatment of AMPK inhibitor, the level of HCV core protein
      decreased by metformin can be rescued. In conclusion, metformin activates type I
      interferon signaling and inhibits the replication of HCV via activation of AMPK.

PMID- 29190885
TI  - The IDO inhibitor 1-methyl tryptophan activates the aryl hydrocarbon receptor
      response in mesenchymal stromal cells.
AB  - The catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is a key
      step in tolerance effected by a variety of cell types, including mesenchymal
      stromal cells (MSCs). Trp catabolism generates molecules known as kynurenines,
      whose tolerance mechanisms involve activation of the Aryl Hydrocarbon Receptor
      (AHR). A synthetic analog of Trp, 1-methyl tryptophan (1MT), is a selective
      inhibitor of IDO enzymatic activity being utilized in cancer immunotherapy
      trials. We hypothesized 1MT might activate AHR independently of its effects on
      IDO. We demonstrate MSCs express AHR protein, and that in vitro treatment with
      1MT causes AHR nucleotranslocation. Upon analyzing mRNA, we observed
      transcriptional upregulation of cytochrome p450 1a1 and 1b1 by 1MT racemic
      mixture (R-MT), consistent with AHR-activation. RNA-sequencing identified Nrf2,
      MAPK12 and IL-1a as downstream targets of 1MT. We demonstrate 1a1 and 1b1
      activation by 1MT in IDO+ MSC following interferon-gamma (IFN-gamma) activation,
      suggesting AHR signaling is uncoupled from IDO catalytic function. Such a
      mechanism of action for 1MT may extend its usage to a wider range of patients,
      irrespective of tumor IDO expression. These observations support a novel paradigm
      by which AHR-activating compounds like 1MT can be used in cancer immunotherapy to
      stimulate a pro-inflammatory response.

PMID- 29190887
TI  - MiR-205 as a promising biomarker in the diagnosis and prognosis of lung cancer.
AB  - MicroRNA-205 (miR-205) was revealed as a novel diagnostic and prognostic
      biomarker for lung cancer, but the results in the published papers were
      inconsistent. This meta-analysis aimed to investigate the diagnostic and
      prognostic roles of miR-205 in patients with lung cancer. Totally, 16 eligible
      articles were included, among which 10 articles investigated the diagnostic value
      of miR-205, 5 articles examined its prognostic values, and 1 article studied both
      diagnostic and prognostic values. For the diagnostic meta-analysis, the pooled
      sensitivity, specificity, positive likelihood ratio, negative likelihood ratio,
      diagnostic odds ratio, and the overall area under the curve of miR-205 for
      patients with lung cancer were 0.88 (95% CI = 0.78 - 0.94), 0.78 (95% CI = 0.66 -
      0.86), 4.00 (95% CI = 2.47 - 6.49), 0.16 (95% CI = 0.08 - 0.30), 25.86 (95% CI =
      9.29 - 71.95), and 0.90 (95% CI = 0.87 - 0.92), respectively, indicating that miR
      205 is a useful biomarker for diagnostic of lung cancer. The subgroup analysis
      further demonstrated that miR-205 had an excellent overall accuracy for detection
      with tissue samples compare with blood samples. For the prognostic meta-analysis,
      the pooled outcome of the disease-free survival and recurrence-free survival
      analyses revealed that increased miR-205 levels had a protective role in the
      prognosis of patients with lung cancer (pooled HR = 0.86, 95% CI: 0.78-0.96, z =
      2.83, P = 0.005). In conclusion, miR-205 may be a promising biomarker for
      detection, predicting the recurrence of patients with lung cancer.

PMID- 29190888
TI  - Genomic profiles of a hepatoblastoma from a patient with Beckwith-Wiedemann
      syndrome with uniparental disomy on chromosome 11p15 and germline mutation of APC
      and PALB2.
AB  - Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder mainly
      associated with altered genomic imprinting at chromosome 11p15.5. Children with
      BWS, especially uniparental disomy (UPD) at 11p15.5, are at increased risk of
      embryonal tumors including hepatoblastoma. Although genetic alterations of
      sporadic hepatoblastomas have been identified, integrated germline and somatic
      alterations of BWS-related hepatoblastoma have not been reported. For this, we
      performed whole-exome sequencing and genome-wide loss of heterozygosity/copy
      number analyses using a single nucleotide polymorphism (SNP) array for a
      hepatoblastoma in a BWS infant with paternal UPD at chromosome 11p15.5. We found
      germline 11p15.5 UPD as well as germline mutations of APC and PALB2 in the
      patient. At the somatic level, we found a CTNNB1 hotspot mutation and chromosome
      1q gain in the tumor. The development of hepatoblastoma in this case might be
      explained by predisposition of the germline events (11p15.5 UPD, mutations of APC
      and PALB2) and later by somatic events with CTNNB1 somatic mutation and 1q gain.
      To our knowledge, this is the first report of germline and somatic genomic
      alteration profiles in hepatoblastoma arising from BWS. Clinically, our results
      provide a rationale for performing a more strict and intense protocol for
      hepatoblastoma surveillance in a high-risk BWS infant, such as the UPD-carrying
      case, for early detection and treatment.

PMID- 29190889
TI  - Aberrant brain grey matter volume patterns differ among Chinese Han drug-naive
      depression patients with acute and chronic stress.
AB  - Chronic or acute stress can induce structural changes and brain alterations
      associated with the neural mechanisms of depression. Aimed to investigate the GMV
      alterations in the drug-naive depression patients with chronic and acute stress
      experience,we enrolled fifty depression patients with acute stress experience,
      fifty five depression patients with chronic stress experience and forty seven
      healthy controls(HC) to participant in the present study. We used voxel-based
      morphometry to analyze the brain grey matter volume (GMV) alterations. Compared
      with the HC, the patients with acute stress and those with chronic stress
      exhibited a distinct GMV impairment pattern. Widespread, decreased GMV was
      detected in most of the cerebral cortex in all the depression patients.
      Importantly, the greatest finding in our study is that the decreased GMV in the
      depression patients with chronic stress was more widespread than that in the
      patients with acute stress. All brain regions with decreased GMV participated in
      the regulation of emotions, memory, and executive function processing, which is
      consistent with previous findings. There was no significant difference between
      the major depression disorder patients with acute stressful life events and those
      with chronic stressful life events, and this finding largely weakens the support
      of our current conclusion. Thus, we cannot confirm this postulation. However, our
      findings probably indicate that GMV may be more sensitive to major depression
      disorder patients when compared to healthy controls, it did not sensitive when in
      the comparison of patient's group. Overall, our findings provide important
      information for the use of appropriate treatment methods to address acute stress
      and alleviate chronic stress in patients with depression, and such treatments can
      delay the deterioration of the affected brain regions and improve remission
      rates. More importantly, all the inexplicable findings in the present study
      encourage us to conduct a follow-up study to describe the developmental
      trajectory of the pathological brain features of depression patients and explore
      therapeutic targets for future personalized treatment.

PMID- 29190890
TI  - Administration of alpha-ketoglutarate improves epithelial restitution under
      stress injury in early-weaning piglets.
AB  - Alpha-ketoglutarate (AKG) is an important cellular metabolite that participates
      in energy production and amino acid metabolism. However, the protective effects
      and mechanism of AKG on mucosal lesions have not been well understood. This study
      was conducted to investigate the effects of dietary AKG supplementation on
      epithelial restitution in early-weaning piglets under Escherichia coli
      lipopolysaccharide (LPS) induction. A total of 32 weaned piglets were used in a 2
      * 2 factorial design; the major factors were dietary treatment (basal diet or AKG
      diet) and inflammatory challenge (LPS or saline). The results showed that AKG
      supplementation improved the growth performance and intestinal morphology in the
      LPS-induced early-weaning piglets. Compared with the basal diet, the AKG diet
      remarkably decreased the concentration and mRNA expression of intestinal
      inflammatory cytokines (IL-1beta, IL-6, and IL-12) in the LPS-induced piglets.
      Moreover, AKG administration upregulated the mRNA expression of nutrient-sensing
      transporters (GLUT-2, SGLT-1, PEPT-1, I-FABP2) in the small intestine of both
      saline- and LPS-treated piglets, and improved the distribution and expression of
      tight-junction genes andproteins (ZO-1, Occludin, Claudins, E-cadherin).
      Collectively, our findings indicate that AKG has the potential to alleviate
      intestinal inflammatory response and improve epithelial restitution and nutrient
      sensing ability under stress injury in early-weaning piglets, and it also
      provides an experimental basis for enteral use of AKG in swine production and
      clinical application to prevent intestinal epithelial damage.

PMID- 29190891
TI  - High bone marrow ID2 expression predicts poor chemotherapy response and prognosis
      in acute myeloid leukemia.
AB  - Dysregulation of ID proteins is a frequent event in various human cancers and has
      a direct role in cancer initiation, maintenance, progression and drug resistance.
      Our previous study has revealed ID1 expression and its prognostic value in acute
      myeloid leukemia (AML). Herein, we further reported ID2 expression and its
      clinical significance in AML. Real-time quantitative PCR was performed to detect
      ID2 transcript level in bone marrow mononuclear cells of 145 de novo AML
      patients. ID2 expression was significantly up-regulated in AML patients compared
      with controls. ID2 overexpression occurred with the highest frequency in poor
      karyotype (10/17, 59%), lower in intermediate karyotype (35/83, 42%), and the
      lowest in favorable karyotype (7/40, 18%). Moreover, high ID2 expression
      correlated with lower complete remission (CR) rate, shorter overall survival, and
      acted as an independent prognostic biomarker in whole-cohort AML and non-M3-AML
      patients. Importantly, the prognostic value of ID2 expression in AML was
      validated by The Cancer Genome Atlas (TCGA) data. In the follow-up of patients,
      ID2 expression at CR phase was decreased than at the time of diagnosis, and was
      increased again at the time of relapse. These findings demonstrated that bone
      marrow ID2 overexpression was a frequent event in AML patients, and predicts poor
      chemotherapy response and prognosis.

PMID- 29190892
TI  - LncRNA H19 is a major mediator of doxorubicin chemoresistance in breast cancer
      cells through a cullin4A-MDR1 pathway.
AB  - Development of chemoresistance is a persistent problem during cancer treatment.
      Long non-coding RNAs (LncRNAs) are currently emerging as an integral functional
      component of the human genome and as critical regulators of cancer development
      and progression. In the present study, we investigated the role and molecular
      mechanism of H19 lncRNA in chemoresistance development by using doxorubicin (Dox)
      resistance in breast cancer cells as a model system. H19 lncRNA expression was
      significantly increased in anthracycline-treated and Dox-resistant MCF-7 breast
      cancer cells. This H19 overexpression was contributed to cancer cell resistance
      to anthracyclines and paclitaxel as knockdown of H19 lncRNA by a specific H19
      shRNA in Dox-resistant cells significantly improved the cell sensitivity to
      anthracyclines and paclitaxel. Furthermore, gene expression profiling analysis
      revealed that a total of 192 genes were associated with H19-mediated Dox
      resistance. These genes were enriched in multiple KEGG pathways that are related
      to chemoresistance. Using genetic and pharmacological approaches, we demonstrated
      that MDR1 and MRP4 were major effectors of H19-regulated Dox resistance in breast
      cancer cells as MDR1 and MRP4 expression was markedly elevated in Dox-resistant
      cells while dramatically reduced when H19 was knocked down. Moreover, we found
      that CUL4A, an ubiquitin ligase component, was a critical factor bridging H19
      lncRNA to MDR1 expression, and a high tumor CUL4A expression was associated with
      low survival in breast cancer patients treated with chemotherapy. These data
      suggest that H19 lncRNA plays a leading role in breast cancer chemoresistance,
      mediated mainly through a H19-CUL4A-ABCB1/MDR1 pathway.

PMID- 29190893
TI  - Effect of PGE2-EPs pathway on primary cultured rat neuron injury caused by
      aluminum.
AB  - To observe the characteristic changes of PGE2-EPs pathway and divergent functions
      of PGE2 receptor subtypes on neuronal injury. The primary cultured rat
      hippocampus neuron injury model was established via aluminum maltolate (100 MUM).
      The aluminum-overload neurons were treated with the agonists of EP1 (17-phenyl
      trinor Prostaglandin E2 ethyl amide), EP2 (Butaprost), EP3 (Sulprostone) and EP4
      (CAY10598) and antagonists of EP1 (SC-19220), EP2 (AH6809) and EP4 (L-161982) at
      different concentrations, respectively. The neuronal viability, lactate
      dehydrogenase leakage rate and PGE2 content were detected by MTT assay, lactate
      dehydrogenase assay kit and enzyme-linked immunosorbent assay, respectively. The
      mRNA and protein expressions of mPGES-1 and EPs were determined by RT-PCR and
      western blot, respectively. The pathomorphology was identified by hematoxylin
      eosin staining. In the model group, neuronal viability significantly decreased,
      while lactate dehydrogenase leakage rate and PGE2 content increased. The mPGES-1,
      EP1, EP2 and EP4 mRNA expression, and the mPGES-1, EP1 and EP2 protein expression
      increased, while EP3 level decreased. EP3 agonist exerted protective function in
      neuronal viability and lactate dehydrogenase leakage rate, while EP1 agonist, EP2
      and EP4 antagonist exerted an opposite effect. In conclusion, aluminum-overload
      caused an imbalance of PGE2-EP1-4 pathway and activation of EP receptor may
      provide a viable therapeutic target in neuronal injury.

PMID- 29190894
TI  - MicroRNA-212/ABCG2-axis contributes to development of imatinib-resistance in
      leukemic cells.
AB  - BCR-ABL-independent resistance against tyrosine kinase inhibitor is an emerging
      problem in therapy of chronic myeloid leukemia. Such drug resistance can be
      linked to dysregulation of ATP-binding cassette (ABC)-transporters leading to
      increased tyrosine kinase inhibitor efflux, potentially caused by changes in
      microRNA expression or DNA-methylation. In an in vitro-imatinib-resistance model
      using K-562 cells, microRNA-212 was found to be dysregulated and inversely
      correlated to ABC-transporter ABCG2 expression, targeting its 3'-UTR. However,
      the functional impact on drug sensitivity remained unknown. Therefore, we
      performed transfection experiments using microRNA-mimics and -inhibitors and
      investigated their effect on imatinib-susceptibility in sensitive and resistant
      leukemic cell lines. Under imatinib-treatment, miR-212 inhibition led to enhanced
      cell viability (p = 0.01), reduced apoptosis (p = 0.01) and cytotoxicity (p =
      0.03). These effects were limited to treatment-naive cells and were not observed
      in cells, which were resistant to various imatinib-concentrations (0.1 MUM to 2
      MUM). Further analysis in treatment-naive cells revealed that miR-212 inhibition
      resulted in ABCG2 upregulation and increased ABCG2-dependent efflux. Furthermore,
      we observed miR-212 promoter hypermethylation in 0.5 and 2 MUM IM-resistant
      sublines, whereas ABCG2 methylation status was not altered. Taken together, the
      miR-212/ABCG2-axis influences imatinib-susceptibility contributing to development
      of imatinib-resistance. Our data reveal new insights into mechanisms initiating
      imatinib-resistance in leukemic cells.

PMID- 29190895
TI  - Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton
      and PI3K/Akt signaling pathways.
AB  - Silibinin is the major active constituent of silymarin, an extract of milk
      thistle seeds. Silibinin has been shown to have significant anti-cancer effects
      in a variety of malignancies. However, the molecular mechanisms of silibinin
      action in bladder cancer have not been studied extensively. In the present study,
      we found that silibinin (10 MUM) significantly suppressed proliferation,
      migration, invasion and induced apoptosis of T24 and UM-UC-3 human bladder cancer
      cells. Silibinin down-regulated the actin cytoskeleton and phosphatidylinositide
      3-kinase (PI3K)/Akt signaling pathways in these cancer cell lines. These pathways
      were found to crosstalk through RAS cascades. We found that silibinin suppressed
      levels of trimethylated histone H3 lysine 4 and acetylated H3 at the KRAS
      promoter. Furthermore, silibinin targets long non-coding RNA: HOTAIR and ZFAS1,
      which are known to play roles as oncogenic factors in various cancers. This study
      shows that silibinin exerts anti-cancer effects through down-regulation of actin
      cytoskeleton and PI3K/Akt pathways and thus suppresses bladder cancer growth and
      progression.

PMID- 29190897
TI  - Biomarkers identified for prostate cancer patients through genome-scale
      screening.
AB  - Prostate cancer is a threat to men and usually occurs in aged males. Though
      prostate specific antigen level and Gleason score are utilized for evaluation of
      the prostate cancer in clinic, the biomarkers for this malignancy have not been
      widely recognized. Furthermore, the outcome varies across individuals receiving
      comparable treatment regimens and the underlying mechanism is still unclear. We
      supposed that genetic feature may be responsible for, at least in part, this
      process and conducted a two-cohort study to compare the genetic difference in
      tumorous and normal tissues of prostate cancer patients. The Gene Expression
      Omnibus dataset were used and a total of 41 genes were found significantly
      differently expressed in tumor tissues as compared with normal prostate tissues.
      Four genes (SPOCK3, SPON1, PTN and TGFB3) were selected for further evaluation
      after Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway
      analysis and clinical association analysis. MIR1908 was also found decreased
      expression level in prostate cancer whose target genes were found expressing in
      both prostate tumor and normal tissues. These results indicated that these
      potential biomarkers deserve attention in prostate cancer patients and the
      underlying mechanism should be further investigated.

PMID- 29190896
TI  - Cofilin 1 promotes bladder cancer and is regulated by TCF7L2.
AB  - Earlier reports demonstrated that Cofilin expression is increased in bladder
      cancer samples, though its function remains unknown. Here, we found that Cofilin
      1 expression was higher in bladder cancer tissues than in paracancerous tissues.
      Overexpression of Cofilin 1 promoted, while Cofilin 1 knockdown inhibited,
      proliferation, migration, and invasion in the T24 and RT4 bladder cancer cell
      lines. In addition, Cofilin 1 overexpression increased, while Cofilin 1 knockdown
      decreased, bladder tumor volumes in mouse xenograft experiments. Transcription
      factor 7-like 2 (TCF7L2) targeted the promoter of the Cofilin 1 gene, and TCF7L2
      knockdown or mutations in the Cofilin 1 promoter dramatically decreased Cofilin 1
      transcription. TCF7L2 promoted cell proliferation and migration and increased
      Cofilin 1 protein levels in RT4 and T24 cells. Thus, TCF7L2 contributed to
      Cofilin 1-induced promotion of bladder cancer development by binding to the
      Cofilin 1 promoter and increasing its expression.

PMID- 29190898
TI  - Trimedazidine alleviates pulmonary artery banding-induced acute right heart
      dysfunction and activates PRAS40 in rats.
AB  - The molecular mechanism underlying acute right heart failure (RHF) is poorly
      understood. We used pulmonary artery banding (PAB) to induce acute RHF
      characterized by a rapid rise of right ventricular pressure, and then a decrease
      in right ventricular pressure along with a decrease in blood pressure right after
      banding. We found higher brain natriuretic peptide (BNP) and beta-myosin heavy
      chain (betaMHC) levels and lower alpha-myosin heavy chain (alphaMHC) levels in
      RHF rats than sham-operated rats. Hemodynamic indexes in rats with acute RHF were
      slightly improved by trimedazidine TMZ, a key inhibitor of fatty acid (FA)
      oxidation. TMZ also reversed downregulation of peroxisome proliferator-activated
      receptor gamma coactivator 1-beta (PGC-1beta) and peroxisome proliferator
      activated receptor alpha (PPARalpha) by PAB and up-regulates peroxisome
      proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha),
      peroxisome proliferator-activated receptor delta (PPARdelta) and pyruvate
      dehydrogenase kinase isoform 4 (PDK4). In addition, TMZ reversed upregulation of
      phosphorylated Akt by PAB and increased phosphorylated proline-rich Akt-substrate
      40 (PRAS40). Autophagy and apoptosis were not modified by PAB or TMZ. An acute
      RHF model was established in rats through 70% constriction of the pulmonary
      artery. TMZ treatment alleviated PAB-induced acute RHF by activating PRAS40 and
      upregulatingPGC-1alpha, PGC-1beta, PPARalpha, PPARdelta, and PDK4.

PMID- 29190899
TI  - Targeting myocyte-specific enhancer factor 2D contributes to the suppression of
      cardiac hypertrophic growth by miR-92b-3p in mice.
AB  - The role of microRNA-92b-3p (miR-92b-3p) in cardiac hypertrophy was not well
      illustrated. The present study aimed to investigate the expression and potential
      target of miR-92b-3p in angiotensin II (Ang-II)-induced mouse cardiac
      hypertrophy. MiR-92b-3p was markedly decreased in the myocardium of Ang-II
      infused mice and of patients with cardiac hypertrophy. However, miR-92b-3p
      expression was revealed increased in Ang-II-induced neonatal mouse
      cardiomyocytes. Cardiac hypertrophy was shown attenuated in Ang-II-infused mice
      received tail vein injection of miR-92b-3p mimic. Moreover, miR-92b-3p inhibited
      the expression of atrial natriuretic peptide (ANP), skeletal muscle alpha-actin
      (ACTA1) and beta-myosin heavy chain (MHC) in Ang-II-induced mouse cardiomyocytes
      in vitro. Myocyte-specific enhancer factor 2D (MEF2D), which was increased in Ang
      II-induced mouse hypertrophic myocardium and cardiomyocytes, was identified as a
      target gene of miR-92b-3p. Functionally, miR-92b-3p mimic, consistent with MEF2D
      siRNA, inhibited cell size increase and protein expression of ANP, ACTA1 and beta
      MHC in Ang-II-treated mouse cardiomyocytes. Taken together, we demonstrated that
      MEF2D is a novel target of miR-92b-3p, and attenuation of miR-92b-3p expression
      may contribute to the increase of MEF2D in cardiac hypertrophy.

PMID- 29190900
TI  - Immuno-PET imaging based radioimmunotherapy in head and neck squamous cell
      carcinoma model.
AB  - The epidermal growth factor receptor (EGFR) is one of the most comprehensively
      studied molecular targets in head and neck squamous cell carcinoma (HNSCC).
      However, inherent and acquired resistance are serious problems and are
      responsible for limited clinical efficacy and tumor recurrence. In this study, we
      evaluated the feasibility of immuno-positron emission tomography (PET) imaging
      and radioimmunotherapy (RIT) with 64Cu-/177Lu-PCTA-cetuximab in cetuximab
      resistant SNU-1066 HNSCC xenografted model. The cellular uptake of 64Cu/177Lu
      3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-triene-3,6,9,-triacetic
      acid (PCTA)-cetuximab showed good correlation with western blot and flow
      cytometry analysis in EGFR expression level of various HNSCC cells. 177Lu-PCTA
      cetuximab selectively killed cetuximab-resistant SNU-1066 cells in vitro. 64Cu
      /177Lu-PCTA-cetuximab specifically accumulated in SNU-1066 tumor and those
      uptakes were peaked at 48 h and 7 day, respectively in biodistribution, PET and
      single-photon emission computed tomography/computed tomography (SPECT/CT)
      imaging. RIT with single dose of 177Lu-PCTA-cetuximab exhibited significant tumor
      regression and markedly reduced 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) uptake,
      compared to other groups. Proliferation index were dramatically decreased and
      apoptotic index increased in RIT group. These results suggest that a diagnostic
      and therapeutic convergence radiopharmaceutical, 64Cu-/177Lu-PCTA-cetuximab has
      the potential of target selection using immuno-PET imaging and targeted therapy
      by RIT in EGFR expressing cetuximab-resistant HNSCC tumors.

PMID- 29190901
TI  - KIF11 is required for proliferation and self-renewal of docetaxel resistant
      triple negative breast cancer cells.
AB  - Development of chemoresistance remains a major hurdle for triple negative breast
      cancer treatment. Previous studies suggest that CD44+/CD24- cells, subpopulation
      of cancer stem cells with self-renewing and tumor-initiating capacities, are
      partly responsible for chemoresistance and therapeutic failure of triple negative
      breast cancer. Therefore, novel agents that target cancer stem cells (CSCs) may
      improve the clinical outcome. KIF11 (kinesin family member 11), overexpressed in
      many cancer cells, is a molecular motor protein that plays essential role in
      mitosis. In this study, we assess its role in docetaxel resistant triple negative
      breast cancer (TNBC). We found that the expression of KIF11 was significantly
      increased in CD44+/CD24- subpopulation of docetaxel resistant TNBC cells.
      Knockdown of KIF11 resulted in a significant decrease in the percentage of CSCs
      and mammosphere formation. KIF11 knockdown also inhibits cell growth and induces
      cell cycle G2/M arrest followed by cell mitosis and apoptosis. Further docetaxel
      resistant TNBC xenograft models demonstrated that KIF11 inhibitor exerts growth
      inhibitory effect in vivo. Of note, we also found that KIF11 was highly expressed
      in TNBC and its expression was correlated with shorter disease free survival
      time. All these data indicate that KIF11 is critical for proliferation and self
      renewal in TNBC tumor cells in vitro and in vivo, suggesting that KIF11 may be a
      promising therapeutic target for treating chemoresistant TNBC.

PMID- 29190902
TI  - MicroRNA-212 inhibits the proliferation, migration and invasion of renal cell
      carcinoma by targeting X-linked inhibitor of apoptosis protein (XIAP).
AB  - MicroRNAs have been found to be critical regulator of cancer cell biology.
      MicroRNA-212 (miR-212) was identified to be a critical cancer-associated microRNA
      playing either oncogenic functions or tumor suppressive roles in different types
      of human cancers. In this study, we found that the level of miR-212 in renal cell
      carcinoma (RCC) tissues was significantly lower than that in adjacent non-tumor
      tissues. Decreased level of miR-212 was associated with advanced T stage and TNM
      stage of RCC. The expression of miR-212 was decreased in RCC cell lines as
      compared with the HK-2 cell line. Overexpression of miR-212 inhibited cell
      viability, proliferation, migration and invasion of CAKI-2 cells. Knockdown of
      miR-212 increased cell viability and proliferation, migration and invasion of
      ACHN cells. In vivo experiments showed that miR-212 inhibited the proliferation
      and promoted the apoptosis of ACHN cells in nude mice and thus inhibited the in
      vivo tumor growth of CAKI-2 cells. Furthermore, we confirmed that X-linked
      inhibitor of apoptosis protein (XIAP) was the downstream target of miR-212. The
      expression level of miR-212 was negatively correlated with XIAP expression in RCC
      tissues. Moreover, XIAP mediated the tumor suppressive roles of miR-212 in RCC.
      Finally, we demonstrated that the aberrant expression of miR-212 and XIAP was
      evidently correlated with poor prognosis of RCC patients. In all, miR-212 can act
      as a prognostic biomarker for RCC patients and inhibits the growth and metastasis
      of RCC cells by inhibiting XIAP.

PMID- 29190903
TI  - Downregulation of tumor suppressive microRNAs in vivo in dense breast tissue of
      postmenopausal women.
AB  - Women with dense breast tissue on mammography are at higher risk of developing
      breast cancer but the underlying mechanisms are not well understood. De
      regulation of microRNAs (miRNAs) has been associated with the onset of breast
      cancer. miRNAs in the extracellular space participate in the regulation of the
      local tissue microenvironment. Here, we recruited 39 healthy postmenopausal women
      attending their mammography-screen that were assessed having extreme dense or
      entirely fatty breasts (nondense). Microdialysis was performed in breast tissue
      and a reference catheter was inserted in abdominal subcutaneous fat for local
      sampling of extracellular compounds. Three miRNAs, associated with tumor
      suppression, miR-193b, miR-365a, and miR-452 were significantly down-regulated in
      dense breast tissue compared with nondense breast tissue. In addition, miR-452
      exhibited significant negative correlations with several pro-inflammatory
      cytokines in vivo, which was confirmed in vitro by overexpression of miR-452 in
      breast cancer cells. No differences were found of miR-21, -29a, -30c, 146a, 
      148a, -203, or -451 in breast tissue and no miRs were different in plasma.
      Extracellular miRNAs may be among factors that should be included in studies of
      novel prevention strategies for breast cancer.

PMID- 29190904
TI  - Measurements of heterotypic associations between cluster of differentiation CD74
      and CD44 in human breast cancer-derived cells.
AB  - Interactions between pairs of membrane-bound receptors can enhance tumour
      development with implications for targeted therapies for cancer. Here we
      demonstrate clear heterotypic interaction between CD74 and CD44, which might act
      in synergy and hence contribute to breast cancer progression. CD74, a type II
      transmembrane glycoprotein, is a chaperone for MHC class II biosynthesis and a
      receptor for the MIF. CD44 is the receptor for hyaluronic acid and is a Type I
      transmembrane protein. Interactions between CD74, MIF and the intra-cytoplasmic
      domain of CD44 result in activation of ERK1/2 pathway, leading to increased cell
      proliferation and decreased apoptosis. The level of CD44 in the breast tumor cell
      lines CAMA-1, MDA-MB-231, MDA-MB-435 and the immortalized normal luminal cell
      line 226LDM was higher than that of CD74. It was also observed that CD74 and CD44
      exhibit significant variation in expression levels across the cells. CD74 and
      CD44 were observed to accumulate in cytoplasmic compartments, suggesting they
      associate with each other to facilitate tumour growth and metastasis. Use of a
      novel and validated colocalisation and image processing approach, coupled with co
      immunoprecipitation, confirmed that CD74 and CD44 physically interact, suggesting
      a possible role in breast tumour growth. This is the first time that CD74 and
      CD44 colocalization has been quantified in breast cancer cells using a non
      invasive and validated bioimaging procedure. Measuring the co-expression levels
      of CD74 and CD44 could potentially be used as a 'biomarker signature' to monitor
      different stages of breast cancer.

PMID- 29190905
TI  - The exon 38-containing ARHGEF11 splice isoform is differentially expressed and is
      required for migration and growth in invasive breast cancer cells.
AB  - Breast cancer invasion involves the loss of cell-cell junctions and acquisition
      of an invasive, migratory phenotype, and breast cancer cells of the basal
      intrinsic subtype are more invasive and metastatic than breast cancer cells of
      other subtypes. ARHGEF11 is a RhoGEF that was previously shown to bind to the
      tight junction protein ZO-1 at perijunctional actomyosin ring (PJAR), a network
      of cortically organized actin and myosin filaments associated with junctional
      complexes that regulates cell-cell adhesion and polarization. We show here that
      ARHGEF11 shows splice isoform expression that differs according to the intrinsic
      subtype of breast cancer cells and that controls their invasive phenotype.
      Luminal subtype breast cancer cells express the isoform of ARHGEF11 lacking exon
      38 (38-), which binds to ZO-1 at PJAR and is necessary for formation and
      maintenance of cell-cell junctions. Basal subtype breast cancer cells express the
      isoform of ARHGEF11 containing exon 38 (38+), which does not bind to ZO-1 and
      which drives cell migration and motility. Depletion of ARHGEF11 in basal subtype
      breast cancer cells is sufficient to alter cell morphology from a mesenchymal
      stellate form with extensive cell protrusions to a cobblestone-like epithelial
      form, and to suppress growth and survival both in vitro and in vivo. These
      findings show that the expression of the particular splice isoform of ARHGEF11 is
      critically linked to the malignant phenotype of breast cancer cells, identifying
      ARHGEF11 exon 38(+) as a biomarker and target for therapy of breast cancer.

PMID- 29190906
TI  - Improved prognostic stratification using NCCN- and GELTAMO-international
      prognostic index in patients with diffuse large B-cell lymphoma.
AB  - The National Comprehensive Cancer Network (NCCN)-International Prognostic Index
      (IPI) and GELTAMO (Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea)
      IPI were developed to enable better risk prediction of patients with diffuse
      large B-cell lymphoma (DLBCL). The present study compared the effectiveness of
      risk prediction between IPI, NCCN-IPI, and GELTAMO-IPI in patients with DLBCL
      particularly in terms of determining high-risk patients. Among 439 patients who
      were enrolled to a prospective DLBCL cohort treated with R-CHOP
      immunochemotherapy, risk groups were classified according to the three IPIs and
      the prognostic significance of individual IPI factors and IPI models were
      analyzed and compared. All three IPI effectively separated the analyzed patients
      into four risk groups according to overall survival (OS). Estimated 5-year OS of
      patients classified as high-risk according to the IPI was 45.7%, suggesting that
      the IPI is limited in the selection of patients who are expected to have a poor
      outcome. In contrast, the 5-year OS of patients stratified as high-risk according
      to NCCN- and GELTAMO-IPI was 31.4% and 21.9%, respectively. The results indicate
      that NCCN- and GELTAMO-IPI are better than the IPI in predicting patients with
      poor prognosis, suggesting the superiority of enhanced, next-generation IPIs for
      DLBCL.

PMID- 29190907
TI  - Profile of differentially expressed Toll-like receptor signaling genes in the
      natural killer cells of patients with Sezary syndrome.
AB  - Sezary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell
      lymphoma, usually results in shortened survival. Improving innate immunity in SS
      by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists
      could be an interesting modulatory strategy. We evaluated the NK cell populations
      in SS patients assessing activating and inhibitory receptors expression and
      profiled the differential expression of TLR signaling pathway genes in
      unstimulated NK cells and after TLR7/8 stimulation. We observed preserved
      CD56bright NK cells and a low percentage of CD56dim NK cells in the peripheral
      blood of SS patients compared to those in the healthy control group. Both NK cell
      populations showed down-modulation of NKG2C and NKG2D expression, which was
      associated with high serum levels of the soluble form of NKG2D ligands. In
      contrast, an expansion of "memory" CD57+ NKG2C+ NK cells and high cytomegalovirus
      antibody titers were detected in SS patients. Profiling of the TLR signaling
      genes in NK cells from SS patients showed an abundance of differentially
      expressed genes (DEGs) in NK cells in the unstimulated condition, with mostly up
      regulation of NFkappaB/JNK p38 pathway genes, but there was down-regulation of
      type I (IFN-alpha/beta) and II (IFN-gamma) interferon and IL-12A. After
      activation of NK cells with TLR7/8 agonist, the down-regulated genes correlated
      with the IFN response, and IL-12 became up-regulated, together with other
      antitumor factors. NK cell activation with a dual agonist for TLR7 and TLR8 is
      able to induce the expression of IFN-gamma and type I IFN, which can improve
      immunity in SS patients.

PMID- 29190908
TI  - EGFR-targeted nonviral NIS gene transfer for bioimaging and therapy of
      disseminated colon cancer metastases.
AB  - Liver metastases present a serious problem in the therapy of advanced colorectal
      cancer (CRC), as more than 20% of patients have distant metastases at the time of
      diagnosis with less than 5% being cured. Consequently, new therapeutic approaches
      are of major need together with high-resolution imaging methods that allow highly
      specific detection of small metastases. The unique combination of reporter and
      therapy gene function of the sodium iodide symporter (NIS) may represent a
      promising theranostic strategy for CRC liver metastases allowing non-invasive
      imaging of functional NIS expression and therapeutic application of 131I. For
      targeted NIS gene transfer polymers containing linear polyethylenimine (LPEI),
      polyethylene glycol (PEG) and the epidermal growth factor receptor (EGFR)
      specific ligand GE11 were complexed with human NIS DNA (LPEI-PEG-GE11/NIS). Tumor
      specificity and transduction efficiency were examined in high EGFR-expressing
      LS174T metastases by non-invasive imaging using 18F-tetrafluoroborate (18F-TFB)
      as novel NIS PET tracer. Mice that were injected with LPEI-PEG-GE11/NIS 48 h
      before 18F-TFB application showed high tumoral levels (4.8+/-0.6% of injected
      dose) of NIS-mediated radionuclide uptake in comparison to low levels detected in
      mice that received untargeted control polyplexes. Three cycles of intravenous
      injection of EGFR-targeted NIS polyplexes followed by therapeutic application of
      55.5 MBq 131I resulted in marked delay in metastases spread, which was associated
      with improved animal survival. In conclusion, these preclinical data confirm the
      enormous potential of EGFR-targeted synthetic polymers for systemic NIS gene
      delivery in an advanced multifocal CRC liver metastases model and open the
      exciting prospect of NIS-mediated radionuclide therapy in metastatic disease.

PMID- 29190909
TI  - Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in
      gastric cancer.
AB  - Gastric cancer (GC), one of the most common cancers worldwide, has a high
      mortality rate due to limited treatment options. Identifying novel and promising
      molecular targets is a major challenge that must be overcome if treatment of
      advanced GC is to be successful. Here, we used comparative genomic hybridization
      and gene expression microarrays to examine genome-wide DNA copy number
      alterations (CNAs) and global gene expression in 38 GC samples from old and young
      patients. We identified frequent CNAs, which included copy number gains on
      chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p
      and 21p. The most frequently gained region was 7p21.1 (55%), whereas the most
      frequently deleted region was 21p11.1 (50%). Recurrent highly amplified regions
      17q12 and 7q31.1-7q31.31 harbored two well-known oncogenes: ERBB2 and MET.
      Correlation analysis of CNAs and gene expression levels identified CAPZA2 (co
      amplified with MET) and genes GRB7, MIEN1, PGAP3, and STARD3 (co-amplified with
      ERBB2) as potential candidate cancer-promoting genes (CPGs). Public dataset
      analysis confirmed co-amplification of these genes with MET or ERBB2 in GC tissue
      samples, and revealed that high expression (except for PGAP3) was significantly
      associated with shorter overall survival. Knockdown of these genes using small
      interfering RNA led to significant suppression of GC cell proliferation and
      migration. Reduced GC cell proliferation mediated by CAPZA2 knockdown was
      attributable to attenuated cell cycle progression and increased apoptosis. This
      study identified novel candidate CPGs co-amplified with MET or ERBB2, and
      suggests that they play a functional role in GC.

PMID- 29190910
TI  - The tissue distribution and significance of B7-H4 in laryngeal carcinoma.
AB  - The costimulatory signals CD28 and B7 have been shown to control tumor invasion
      and metastasis by regulating T cell activation, whereas the distribution
      characteristics of B7-associated proteins in laryngeal carcinoma (LC) tissue are
      still unclear. Here, the expression of members of the B7 superfamily, including
      B7-H1 (PD-L1), B7-DC (PD-L2) and B7-H4, in fifty-two LC samples was determined by
      immunohistochemistry, and the relationship between B7-H4 and epithelial
      mesenchymal transition (EMT)-associated markers was further assessed by
      immunofluorescence double staining. Furthermore, the human LC cell lines, Hep-2
      and TU212 cells, were further transfected to overexpress B7-H4, and cell invasion
      and metastasis were analyzed. The results showed that B7-H1, B7-DC and B7-H4 were
      expressed in the tumor cells, and their expression was restricted to the cell
      membrane and the cytoplasm. The positive rates of these molecules in the tumor
      tissues were 57.7% (30/52), 32.7% (17/52) and 34.6% (18/52), respectively.
      Interestingly, double immunofluorescence staining showed that B7-H4 is
      coexpression with EMT-related markers, including p-Smad2/3, Snail and Vimentin,
      in carcinoma cells. Moreover, overexpression of B7-H4 in Hep-2 cells promotes the
      expression of pSmad2/3 and Snail by activating AKT-STAT3 signaling. Transwell and
      wound-healing assays demonstrated that B7-H4 enhanced both Hep-2 and TU212 cell
      invasion and metastasis. Our results suggest that B7-H4 transmits feedback
      signaling to tumor cells and promotes invasion and metastasis by promoting EMT
      progression. Therefore, blocking B7-H4 signaling might be a novel treatment
      strategy for LC.

PMID- 29190911
TI  - Acquisition of EGFR TKI resistance and EMT phenotype is linked with activation of
      IGF1R/NF-kappaB pathway in EGFR-mutant NSCLC.
AB  - Epithelial-mesenchymal transition (EMT) is clinically associated with acquired
      resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKI) in non-small cell lung cancers (NSCLC). However, the mechanisms promoting
      EMT in EGFR TKI-resistant NSCLC have not been fully elucidated. Previous studies
      have suggested that IGF1R signaling is involved in both acquired EGFR TKI
      resistance in NSCLC and induction of EMT in some types of tumor. In this study,
      we further explored the role of the IGF1R signaling in the acquisition of EMT
      phenotype associated with EGFR TKI resistance in mutant-EGFR NSCLC. Compared to
      gefitinib-sensitive parental cells, gefitinib-resistant (GR) cells displayed an
      EMT phenotype associated with increased migration and invasion abilities with the
      concomitant activation of IGF1R and NF-kappaB p65 signaling. Inhibition of IGF1R
      or p65 using pharmacological inhibitor or specific siRNA partially restored
      sensitivity to gefitinib with the concomitant reversal of EMT in GR cells.
      Conversely, exogenous IGF1 induced both gefitinib resistance and accompanying EMT
      in parental cells. We also demonstrated that IGF1R could phosphorylate downstream
      Akt and Erk to activate NF-kappaB p65. Taken together, our findings indicate that
      activation of IGF1R/Akt/Erk/NF-kappaB signaling is linked to the acquisition of
      EGFR TKI resistance and EMT phenotype in EGFR-mutant NSCLC and could be a novel
      therapeutic target for advanced NSCLC.

PMID- 29190913
TI  - Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK)
      in non-small cell lung cancer.
AB  - The anaplastic lymphoma kinase (ALK) is recognized by the immune system as a
      tumor antigen, and preclinical evidence suggests that ALK-rearranged NSCLCs can
      also be successfully targeted immunologically using vaccine-based approaches. In
      contrast to ALK-rearranged lymphomas, the frequency and clinical significance of
      spontaneous ALK immune responses in patients with ALK-rearranged NSCLCs are
      largely unknown. We developed an enzyme-linked immunosorbent assay (ELISA) to
      measure anti-ALK antibody levels and mapped specific peptide epitope sequences
      within the ALK cytoplasmic domain in patients with non-small cell lung cancer.
      The ELISA method showed good correlation with ALK antibody titers measured with a
      standard immunocytochemical approach. Strong anti-ALK antibody responses were
      detected in 9 of 53 (17.0%) ALK-positive NSCLC patients and in 0 of 38 (0%) ALK
      negative NSCLC patients (P<0.01), and the mean antibody levels were significantly
      higher in ALK-positive than in ALK-negative NSCLC patients (P=0.02). Across
      individual patients, autoantibodies recognized different epitopes in the ALK
      cytoplasmic domain, most of which clustered outside the tyrosine kinase domain.
      Whether the presence of high ALK autoantibody levels confers a more favorable
      prognosis in this patient population warrants further investigation.

PMID- 29190912
TI  - RBP4 and THBS2 are serum biomarkers for diagnosis of colorectal cancer.
AB  - The potential role of serum RBP4 and THBS2 as biomarker in colorectal cancer
      (CRC) diagnosis has never been studied. We investigated in large sample using
      quantitative ELISA method to explore whether serum RBP4 and THBS2 can act as
      biomarkers for CRC diagnosis. The concentration of RBP4 and THBS2 was measured in
      402 CRC patients' serum samples and 218 normal controls' serum samples. The
      results showed that the average RBP4 and THBS2 concentrations in normal controls
      were significantly higher than in CRC patients (36.5+/-11.4MUg/mL vs 21.8+/
      8.7MUg/mL and 20.5+/-6.1ng/mL vs 14.5+/-7.3ng/mL, respectively), both p<0.001.
      RBP4 distinguished CRC patients from normal individuals with the area under the
      receiver operating characteristic curve (AUC) performing at 0.852, with
      sensitivity of 74.9% and specificity of 81.7%. While THBS2 distinguished CRC
      patients performing AUC at 0.794, with sensitivity of 64.9% and specificity of
      87.1%. The ability of RBP4 and THBS2 serum concentration distinguishing CRC from
      normal controls showed better than that of serum CEA (AUC=0.818) or CA19-9
      (AUC=0.650) concentration. This is the first study to report RBP4 and THBS2 as
      diagnosis serum biomarkers for CRC, which might be a good supplement for CEA or
      CA19-9 for clinical diagnosis.

PMID- 29190914
TI  - Genomic copy number gains of ErbB family members predict poor clinical outcomes
      in glioma patients.
AB  - The aim of this study was to investigate copy number of ErbB family members
      (including EGFR, HER2, HER3 and HER4) in a cohort of gliomas and benign
      meningiomas (control subjects), and explore the associations of their copy number
      with clinicopathological characteristics and clinical outcomes of glioma
      patients. Using real-time quantitative PCR assay, we demonstrated that copy
      number of EGFR, HER2, HER3 and HER4 in glioma patients was significantly
      increased compared to control subjects. Moreover, our data also showed that the
      risk of cancer-related death was positively associated with copy number gain
      (CNG) of EGFR, HER3 and HER4, but not HER2. CNG of EGFR and HER2 was positively
      related to radiotherapy, while CNG of HER3 and HER4 was negatively related to
      chemotherapy. Importantly, EGFR CNG significantly shortened median survival times
      of glioma patients regardless of gender, tumor grade and therapeutic regimens.
      Stratified analysis showed that CNG of HER2-4 almost did not influence the
      survival of male patients, patients with high-grade tumors and patients receiving
      chemotherapy, but dramatically shortened median survival times of female
      patients, those with low-grade tumors and those receiving radiotherapy.
      Collectively, our data not only demonstrate that the members of ErbB family are
      frequently amplified in gliomas, but also suggest that these common genetic
      events may be prognostic factors for poor clinical outcomes in glioma patients.

PMID- 29190915
TI  - The prognostic significance of CD11b+CX3CR1+ monocytes in patients with newly
      diagnosed diffuse large B-cell lymphoma.
AB  - Despite their critical roles in angiogenesis and host immunosuppression within
      the tumor microenvironment, the prognostic significance of myeloid-lineage cells
      expressing CD11b and CX3CR1 in diffuse large B-cell lymphoma (DLBCL) has not been
      well studied. We prospectively enrolled newly-diagnosed DLBCL patients at two
      Korean institutions between May 2011 and Aug 2015. CD11b+CX3CR1+ cells were
      analyzed by flow cytometry using peripheral blood (PB) and bone marrow (BM)
      aspirate samples before treatments. Eighty-nine patients (52 males) were
      enrolled. The median age was 65 years (range, 19-88 years). Thirty-seven patients
      (42%) were classified as high-intermediate or high risk according to the National
      Comprehensive Cancer Network International Prognostic Index (NCCN-IPI). Patients
      were categorized into either high or low PB-/BM-CD11b+CX3CR1+ monocyte group
      according to the cutoffs identified by the receiver-operating-characteristics
      analysis (PB, 3.68%; BM, 3.45%). The high PB-CD11b+CX3CR1+ monocyte group was
      significantly associated with high-intermediate and high risk NCCN-IPI group (P =
      0.004). With a median follow-up of 27.7 months (range, 1.7-60.4 months), the low
      PB-CD11b+CX3CR1+ monocyte group showed significantly better overall survival (OS)
      than the high PB-CD11b+CX3CR1+ monocyte group (3-year, 92.3% vs. 51.2%,
      respectively; P < 0.001). In contrast, no significant difference was observed
      between the high and low BM-CD11b+CX3CR1+ monocyte groups. Among patients with
      high-intermediate to high risk NCCN-IPI, the high PB-CD11b+CX3CR1+ monocyte group
      showed significantly worse OS than the low PB-CD11b+CX3CR1+ monocyte group (3
      year, 29.3% vs. 80.2%, respectively; P = 0.008). Taken together, PB-CD11b+CX3CR1+
      monocyte percentage correlates with the NCCN-IPI risk stratification, which
      enables identification of subgroups with extremely poor clinical outcomes.

PMID- 29190916
TI  - Coenzyme Q10 inhibits the activation of pancreatic stellate cells through
      PI3K/AKT/mTOR signaling pathway.
AB  - Aim: Pancreatic stellate cells (PSCs) have a vital role in pancreatic fibrosis
      accompanied by pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis
      (CP). Any agents which can affect the activation of PSCs could become potential
      candidates for treatment strategies in PDAC and CP. Our aim was to explore the
      effect of Coenzyme Q10 (CoQ10) in the process of PSCs activation. Methods:
      Isolated PSCs from C57BL/6 mice were treated with various dosages of CoQ10 (1,
      10, and 100MUM) and different time (24h, 48h, and 72 h). Effect of CoQ10 on
      autophagy, apoptosis, senescence and oxidative stress, as well as the activation
      of PSCs were analyzed by immunocytofluorescent staining, quantitative real time
      RT-PCR, western blotting, SA-beta-galactosidase staining, malondialdehyde and
      reactive oxygen species (ROS) assay. Results: Expression of alpha-smooth muscle
      actin, LC3II, Beclin1, Cleaved caspases-3 and Bax levels were significantly
      reduced in CoQ10 treatment groups. Meanwhile, compared with the control group,
      significant differences for the expression of desmin, P62, Bcl-2, p-PI3K, p-AKT
      and p-mTOR levels in CoQ10 treatment groups were found. Moreover, CoQ10 affected
      the secretion of extracellular matrix components for PSCs. Few SA-beta-gal
      positive cells were found in CoQ10 treated groups. A significant decrease in ROS
      positive cells and malondialdehyde levels were observed after 72 h exposure to
      CoQ10. Conclusions: Our finding suggests that CoQ10 inhibits the activation of
      PSCs by suppressing autophagy through activating the PI3K/AKT/mTOR signaling
      pathway. CoQ10 may act as a therapeutic agent in PSC-relating pathologies and/or
      anti-fibrotic approaches.

PMID- 29190917
TI  - Pretreatment Epstein-Barr virus DNA in whole blood is a prognostic marker in
      peripheral T-cell lymphoma.
AB  - Because there are few studies regarding the clinical impact of circulating EBV
      DNA in peripheral T-cell lymphomas (PTCLs), we tried to evaluate the role of EBV
      DNA in whole blood as a prognostic factor for PTCL. We retrospectively reviewed
      110 PTCL patients with median age of 63 (20-94) years. Forty-seven patients
      (42.7%) showed positive results for EBV-DNA, and these patients also had stage
      III/IV disease, elevated lactic dehydrogenase, and low albumin level (P = 0.007,
      P = 0.004, P = 0.002, respectively). The 5-year overall survival (OS) and
      progression free survival (PFS) were 21.0% and 18.0%. Univariable analysis showed
      that positive EBV-DNA was related with inferior OS and PFS (P = 0.015 and P <
      0.001, respectively). Multivariable analysis showed that poor performance status,
      extranodal involvement more than one site and positive EBV-DNA results were
      related with OS and PFS (P < 0.001, P < 0.001, P = 0.007 and P = 0.001, P =
      0.002, P < 0.001, respectively). Using these three variables, we made a new
      prognostic model which classified patients on risk as follows: low, no adverse
      factors; intermediate, 1 factor; or high, 2-3 factors. The new prognostic model
      could stratify the three groups for OS and PFS better than either international
      prognostic index or prognostic index of PTCL-u, and showed statistical
      significance in PTCL, not otherwise specified. This study suggests that whole
      blood EBV-DNA is related with aggressive clinical characteristics and inferior
      survival. The new prognostic model, which incorporates EBV-DNA, could better
      stratify PTCL patients.

PMID- 29190918
TI  - Plasma lipid profiling and diagnostic biomarkers for oral squamous cell
      carcinoma.
AB  - Biological requirements for tumor cell proliferation include the sustained
      increase of structural, energetic, signal transduction and biosynthetic
      precursors. Because lipids participate in membrane construction, energy storage,
      and cell signaling. We hypothesized that the differences in lipids between
      malignant carcinoma and normal controls could be reflected in the bio-fluids. A
      total of 100 pre-operative plasma samples were collected from 50 oral squamous
      cell carcinoma (OSCC), 50 normal patients and characterize by lipid profiling
      using ultra performance liquid chromatography/electro spray ionization mass
      spectrometry (UPLC-MS). The lipid profiles of the OSCC and control samples as
      well as the different stages were compared. Differentially expressed lipids were
      categorized as glycerophospholipids and sphingolipids. All glycerophospholipids
      were decreased, especially phosphatidylcholine and phosphoethanolamine
      plasmalogens, whereas sphingolipids were increased in the OSCC patients compared
      to the controls. We further identified 12 staging related lipids, which could be
      utilized to discriminate early stage patients from advanced stage patients. In
      the future, the differential lipids may provide biologists with additional
      information regarding lipid metabolism and guide clinicians in making
      individualized therapeutic decisions if these results are confirmed in a larger
      study.

PMID- 29190919
TI  - Molecular characterization of pro-metastatic functions of beta4-integrin in
      colorectal cancer.
AB  - The beta4-integrin subunit has been implicated in development and progression of
      several epithelial tumor types. However, its role in metastases of colorectal
      cancer (CRC) remains elusive. To study CRC metastasis, we generated a highly
      invasive, metastatic cell line MC38-LM10 (LM10) by passaging mouse CRC MC38 cells
      ten times, using a splenic injection model of liver metastasis. Affymetrix
      microarray analyses of LM10 and MC38 cell lines and their corresponding liver
      metastases generated a gene signature for CRC metastasis. This signature shows
      strong upregulation of beta4-integrin in LM10 cells and corresponding metastases.
      Upregulation of beta4-integrin in highly aggressive LM10 cells is associated with
      increased migration, invasion, and liver metastases. Furthermore, stable
      knockdown of beta4-integrin in human CRC SW620 cells reduces Bcl-2 expression,
      increases apoptosis, and decreases invasion, tumorigenicity, and liver
      metastasis, thus resulting in significantly increased survival of mice (hazard
      ratio = 0.32, 95% confidence interval = 0.15-0.66, P<0.01). Patients with CRC
      tumors display higher beta4-integrin levels in stages 1-4 and significantly lower
      survival rate. Collectively, beta4-integrin plays a critical role in CRC
      progression, invasion, and metastasis, suggesting that it could be a potential
      therapeutic target for CRC patients.

PMID- 29190920
TI  - A cassaine diterpene alkaloid, 3beta-acetyl-nor-erythrophlamide, suppresses VEGF
      induced angiogenesis and tumor growth via inhibiting eNOS activation.
AB  - Angiogenesis is one of the hallmarks of cancer, playing an essential role in
      tumor growth, invasion, and metastasis. 3beta-Acetyl-nor-erythrophlamide (3-ANE),
      a cassaine diterpene alkaloid compound from Erythrophleum fordii, exerts various
      pharmacological effects, including antitumor activity. However, the effects of 3
      ANE on tumor angiogenesis and its potential molecular mechanism are still
      unknown. Here, we demonstrated that 3-ANE inhibited the vascular endothelial
      growth factor (VEGF)-mediated proliferation, migration, invasion, and capillary
      like tube formation of human umbilical vascular endothelial cells (HUVECs),
      without inducing apoptosis. We also found that 3-ANE blocked angiogenesis in
      vivo, and suppressed tumor angiogenesis and human lung adenocarcinoma growth in
      the xenograft tumor model. Furthermore, we showed that 3-ANE blocked VEGF
      mediated endothelial nitric oxide synthase (eNOS) phosphorylation, vascular
      permeability and NO production in HUVECs, via disrupting the VEGF-induced
      association of eNOS and heat-shock protein 90 (HSP90). Our studies therefore
      provide the first evidence that 3-ANE inhibits tumor angiogenesis by inhibiting
      the VEGF-mediated eNOS activation and NO production, and 3-ANE could be a
      potential candidate in angiogenesis-related disease therapy.

PMID- 29190921
TI  - Bisphenol A deteriorates egg quality through HDAC7 suppression.
AB  - Bisphenol A (BPA), a synthetic substance of endocrine disrupter, widely
      distributes in environment and can affect the health of ovarian follicles,
      thereby impacting the fertilization ability and pregnancy rate. However, the
      underlying mechanisms regarding how BPA disrupts the egg quality have not been
      fully revealed. In this study, we determine that BPA treated female mice display
      the decreasing HDAC7 expression in ovary and eggs compared to control. Moreover,
      the global levels of H3K9 and H4K16 acetylation abnormally increase after BPA
      treatment and recover partially upon HDAC7 compensation. Collectively, our study
      reveals that BPA deteriorates egg quality through HDAC7 suppression.

PMID- 29190922
TI  - Effect of ligustrazine on preventing contrast-induced nephropathy in patients
      with unstable angina.
AB  - Objective: Our purpose was to assess the effect of ligustrazine in the prevention
      of contrast-induced nephropathy (CIN) in patients with unstable angina (UA).
      Methods: 148 patients with UA undergoing coronary angiography and/or percutaneous
      coronary intervention (PCI) were selected for observation; the patients were
      divided into a control group (group A, n=74) and a ligustrazine group (group B,
      n=74). Group A was given routine treatment, while group B was given routine
      treatment combined with ligustrazine. Serum creatinine (Scr), cystatin C and
      glomerular filtration rate (eGFR) concentrations were measured before and 1 day,
      2 days and 3 days after treatment, and the incidence of contrast-induced
      nephropathy (CIN) and major cardiovascular events (MACE) were observed in both
      groups. Results: The Scr, Cystatin C and eGRF levels in group B were better than
      in group A after 1 day (OR: 2.64, 95% CI: 2.47-4.98; OR: 2.66, 95% CI: 2.62-5.77;
      OR: 4.02, 95% CI: 3.02-5.53, respectively), 2 days (OR: 3.58, 95% CI: 2.41-4.92;
      OR: 2.92, 95% CI: 2.83-5.02; OR: 3.28, 95% CI: 3.24-5.14, respectively) and 3
      days of treatment (OR: 3.26, 95% CI: 2.17-4.35; OR: 2.85, 95% CI: 2.26-4.02; OR:
      3.19, 95% CI: 2.53-4.34, respectively). The incidence of CIN (9.26% vs 16.67%)
      and MACE (7.41% vs 18.51%) of group B were significantly lower than in group A
      (P<0.05). Conclusions: Our study suggests that ligustrazine can reduce CIN and
      MACE in patients with UA when undergoing coronary angiography and/or PCI.

PMID- 29190923
TI  - Prognostic values of distinct CBX family members in breast cancer.
AB  - Chromobox (CBX) family proteins are canonical components in polycomb repressive
      complexes 1 (PRC1), with epigenetic regulatory function and transcriptionally
      repressing target genes via chromatin modification. A plethora of studies have
      highlighted the function specifications among CBX family members in various
      cancer, including lung cancer, colon cancer and breast cancer. Nevertheless, the
      functions and prognostic roles of distinct CBX family members in breast cancer
      (BC) remain elusive. In this study, we reported the prognostic values of CBX
      family members in patients with BC through analysis of a series of databases,
      including CCLE, ONCOMINE, Xena Public Data Hubs, and Kaplan-Meier plotter. It was
      found that the mRNA expression of CBX family members were noticeably higher in BC
      than normal counterparts. CBX2 was highly expressed in Basal-like and HER-2
      subtypes, while CBX4 and CBX7 expressions were enriched in Luminal A and Luminal
      B subtypes of BC. Survival analysis revealed that CBX1, CBX2 and CBX3 mRNA high
      expression was correlated to worsen relapse-free survival (RFS) for all BC
      patients, while CBX4, CBX5, CBX6 and CBX7 high expression was correlated to
      better RFS in this setting. Noteworthily, CBX1 and CBX2 were associated with
      chemoresistance whereas CBX7 was associated with tamoxifen sensitivity, as well
      as chemosensitivity in breast tumors. Therefore, we propose that CBX1, CBX2 and
      CBX7 are potential targets for BC treatment. The results might be beneficial for
      better understanding the complexity and heterogeneity in the molecular
      underpinning of BC, and to develop tools to more accurately predict the prognosis
      of patients with BC.

PMID- 29190924
TI  - PTTG1 cooperated with GLI1 leads to epithelial-mesenchymal transition in
      esophageal squamous cell cancer.
AB  - Pituitary tumor-transforming gene-1 (PTTG1) could acquire its metastasis
      promoting effects via inducing epithelial-mesenchymal transition (EMT). However,
      its role and mechanism in EMT in esophageal squamous cell cancer (ESCC) had not
      been clearly elucidated. Here, we demonstrated that PTTG1 was overexpressed in
      ESCC cell lines and tissues especially those with lymph node metastasis. Down
      regulation of PTTG1 levels dampened the ESCC cells invasion, migration,
      proliferation ability and colony formation in vitro and inhibited the growth of
      mouse xenograft model of ESCC cells in vivo. In addition, our in vitro and in
      vivo experiments consistently showed that decreased PTTG1 led to the inhibition
      of EMT process. Glioma-associated oncogene homolog1 (GLI1), a key factor in HH
      GLI signaling pathway, was also overexpressed in ESCC cells and tissues.
      Mechanistic studies demonstrated that decreased PTTG1 mitigated the expression
      levels of GLI1 in vitro and in vivo and ChIP assay also indicated that PTTG1
      cooperated with GLI1 by binding to its promoter. Furthermore, overexpression of
      GLI1 rescued the EMT inhibited by down regulation of PTTG1 in vitro. Together,
      these data suggested that PTTG1 promoted the invasion ability of ESCC cells via
      EMT, more important, PTTG1 participated in EMT via activating the expression of
      GLI1 in ESCC. PTTG1 could be a candidate biomarker for defining ESCC metastasis
      and useful target for therapy.

PMID- 29190925
TI  - Nab-paclitaxel plus S-1 in advanced pancreatic adenocarcinoma (NPSPAC): a single
      arm, single center, phase II trial.
AB  - This single-arm, phase II trial is to investigate efficacy and safety of nab
      paclitaxel plus S-1 as first-line treatment in advanced pancreatic cancer. Nab
      paclitaxel was administered at 120 mg/m2 intravenously on day 1 and 8, S-1 was
      given twice a day orally on day 1-14 of each 21-day cycle, for 6 cycles. The
      primary endpoint was objective response rate (ORR), the secondary endpoints were
      progression-free survival (PFS), overall survival (OS) and safety. The ORR in
      intent-to-treat population (N=60) by either blinded independent review (BIR) or
      investigator assessment was 50.0%. Median PFS (mPFS) by BIR and median OS (mOS)
      were 5.6 months (95%CI, 4.6 to 6.6 m) and 9.4 months (95%CI, 8.0 to 10.8m),
      respectively. The most common grade 3 or 4 toxicities were leukopenia/neutropenia
      (35%) and fatigue (8.3%). Subgroup analyses based on BIR showed a remarkable ORR
      (>70%) was achieved in patients with female gender, >= 50% decline from baseline
      CA19-9, and developed grade 3 or 4 leukopenia/neutropenia. Remarkable survival
      benefit was statistically significant in female (mPFS: 7.7m, mOS: 18.2m), >= 50%
      decline from baseline CA19-9 (mPFS: 6.8m, mOS: 11.8m), objective responders
      (mPFS: 6.9m, mOS: 12.2m), and ECOG of 0 at baseline (mPFS: 7.5m, mOS: 16.1m). Nab
      paclitaxel plus S-1 showed encouraging ORR and manageable toxicities, which is an
      effective alternative treatment regimen for advanced pancreatic cancer.
      (https://clinicaltrials.gov/ number, NCT02124317).

PMID- 29190926
TI  - Polymorphism of the ABO gene associate with thrombosis risk in patients with
      paroxysmal nocturnal hemoglobinuria.
AB  - Thrombosis is one of the most common causes of mortality in Paroxysmal nocturnal
      hemoglobinuria (PNH), but the predisposing factors for thrombosis are yet to be
      defined. In this study, we outline the clinical characters and the susceptible
      genes which lead to thrombotic formation in 104 patients with PNH. The results
      displayed that the genotypes with minor alleles of rs495828 or rs2519093 in the
      ABO gene were associated with high risk to thrombus formation (OR 5.95, 95% CI
      1.90-18.65 and OR 6.3, 95% CI 2.01-19.79, respectively). Further, the TT
      haplotype was associated with a significant increased risk of thrombosis
      (OR=3.25, 95%CI 1.42-7.39). Multivariate regression analysis showed larger PNH
      clone and genotypes with rs495828/rs2519093 minor allele as independent risk
      factors for thrombosis in PNH. Some patients who came back for follow-up were
      tested for the plasma levels of vWF and factor VIII. Patients carrying the
      rs495828/rs2519093 minor allele had a significant higher level of vWF and factor
      VIII compared with those carrying the major allele. Therefore, we found for the
      first time that the rs495828/rs2519093 polymorphism represent an independent
      prognostic factor in PNH patients for thrombus formation, probably by increasing
      the vWF and factor VIII.

PMID- 29190927
TI  - Dietary apple pectic oligosaccharide improves gut barrier function of rotavirus
      challenged weaned pigs by increasing antioxidant capacity of enterocytes.
AB  - Rotavirus can lead to decreasing gut barrier function and diarrhea of children
      and young animals. Apple pectic oligosaccharide treatment reduced diarrhea in
      rotavirus-infected piglets. This study was conducted to explore whether apple
      pectic oligosaccharide administration could protect gut barrier function of
      piglets against rotavirus infection. A total of 28 crossbred weaned barrows were
      allotted into 2 treatments fed the diets supplementing 0 and 200 mg/kg apple
      pectic oligosaccharide. Half of pigs in each diet treatment were challenged by
      rotavirus on d 15. The whole duration of this experiment is 18 days. Rotavirus
      challenge increased average diarrhea index, and impaired microbiota in cecal
      digesta, and histology, expressions of tight-junction proteins, mucins and
      glucagon like peptide-2 concentrations, antioxidant capacity, endoplasmic
      reticulum stress, autophagy and apoptosis in jejunal mucosa of piglets. However,
      dietary apple pectic oligosaccharide supplementation relieved effects of
      rotavirus challenge on diarrhea, gut health, and antioxidant capacity,
      endoplasmic reticulum stress, autophagy and apoptosis of jejunal mucosa in
      piglets. These results suggest that apple pectic oligosaccharide administration
      can prevent diarrhea and damage of gut barrier function via improving antioxidant
      capacity that might reduce endoplasmic reticulum stress, autophagy and apoptosis
      of intestinal epithelial cells in rotavirus-infected piglets.

PMID- 29190928
TI  - Prediction model of hepatocellular carcinoma risk in Asian patients with chronic
      hepatitis B treated with entecavir.
AB  - Background: Until now, no risk score could predict hepatocellular carcinoma (HCC)
      in nucleos(t)ide analog (NA)-treated Asian patients. Methods: We enrolled 1325 NA
      naive chronic hepatitis B patients with entecavir monotherapy for >12 months,
      with 883 and 442 patients randomly assigned to the development and validation
      groups, respectively, in the risk model. Results: The cumulative probabilities of
      HCC were 2.4%, 4.1%, and 9.9% after 2, 3, and 5 years of treatment, respectively.
      In the development group, age, platelet counts, and alpha-fetoprotein levels
      after 12 months of treatment were the independent predictors of HCC. We converted
      the Cox proportional hazards regression coefficients for these predictors into
      risk scores and developed the APA-B model, with the total risk scores ranging
      from 0 to 15. The risk scores accurately categorized patients with low (0-5),
      medium (6-9), and high (10-15) risks in the validation group (P <0.001). The
      areas under the receiver operating characteristic curve for predicting HCC risk
      after 2, 3, and 5 years were 0.877, 0.842, and 0.827, respectively, in the
      development group and 0.939, 0.892, and 0.862, respectively, in the validation
      group. Conclusion: The proposed HCC risk prediction model exhibited excellent
      predictive accuracy in NA-naive Asian patients receiving entecavir therapy.

PMID- 29190929
TI  - Whole-lesion ADC histogram and texture analysis in predicting recurrence of
      cervical cancer treated with CCRT.
AB  - Purpose: To explore the value of whole-lesion apparent diffusion coefficient
      (ADC) histogram and texture analysis in predicting tumor recurrence of advanced
      cervical cancer treated with concurrent chemo-radiotherapy (CCRT). Methods: 36
      women with pathologically confirmed advanced cervical squamous carcinomas were
      enrolled in this prospective study. 3.0 T pelvic MR examinations including
      diffusion weighted imaging (b = 0, 800 s/mm2) were performed before CCRT (pre
      CCRT) and at the end of 2nd week of CCRT (mid-CCRT). ADC histogram and texture
      features were derived from the whole volume of cervical cancers. Results: With a
      mean follow-up of 25 months (range, 11 ~ 43), 10/36 (27.8%) patients ended with
      recurrence. Pre-CCRT 75th, 90th, correlation, autocorrelation and mid-CCRT
      ADCmean, 10th, 25th, 50th, 75th, 90th, autocorrelation can effectively
      differentiate the recurrence from nonrecurrence group with area under the curve
      ranging from 0.742 to 0.850 (P values range, 0.001 ~ 0.038). Conclusions: Pre-
      and mid-treatment whole-lesion ADC histogram and texture analysis hold great
      potential in predicting tumor recurrence of advanced cervical cancer treated with
      CCRT.

PMID- 29190930
TI  - MicroRNA-34a functions as a tumor suppressor by directly targeting oncogenic
      PLCE1 in Kazakh esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the frequent malignant tumors
      with poor prognosis worldwide. Identifying the prognostic biomarkers and
      potential mechanisms of such tumors has attracted increasing interest in
      esophageal cancer biology. Our previous study showed that phospholipase C elipson
      1 (PLCE1) expression is up-regulated and associated with disease progression in
      esophageal carcinoma. MicroRNAs (miRNAs) play vital roles in regulating its
      target gene expression. However, studies on miRNA-regulated PLCE1 expression and
      its cellular function are still very few. We found that miR-34a is significantly
      expressed lower in ESCC tissues. We further showed that PLCE1 is a direct
      functional target gene of miR-34a, and the functional roles of miR-34a in ESCC
      cell lines in vitro were also determined through gain- and loss-of-function
      analyses. Results revealed that miR-34a functions as a tumor suppressor by
      inhibiting the proliferation, migration, and EMT phenotype, as well as promoting
      apoptosis of ESCC cell lines. Moreover, PLCE1 is overexpressed in ESCC tumors and
      promotes tumorigenicity in vivo and vitro. PLCE1 expression is negatively
      correlated with miR-34a profiles in ESCC tissues. Our data suggest that miR-34a
      exerts its anti-cancer function by suppressing PLCE1. The newly identified miR
      34a/PLCE1 axis partially illustrates the molecular mechanism of ESCC metastasis
      and represents a new candidate therapeutic target for ESCC treatment.

PMID- 29190931
TI  - Cancer mortality trends in an industrial district of Shanghai, China, from 1974
      to 2014, and projections to 2029.
AB  - We aimed to characterize the trends and projections of cancer mortalities in
      Yangpu, an industry restructuring district of Shanghai, China. With high-quality
      data from the death registration system, the authors analyzed the trends in
      cancer mortalities during 1974-2014 and their relationship with pollution control
      and socioeconomic improvements. Cancer burden was projected into 2029. During
      1974-2014, cancer death accounted for 28.80% of all-cause death. The 5 leading
      causes of cancer death were cancers of the lung & bronchus, stomach, liver, colon
      & rectum, and esophagus. Age-standardized mortality of all cancers was higher in
      men than in women (153.1/105vs. 88.8/105, p<0.001) and increased from 1974 to
      1991 and decreased thereafter. The mortalities of cancers of the larynx, bladder,
      liver, nasopharynx, lung & bronchus, esophagus, lip oral & pharynx, stomach,
      kidney, and lymphoma were significantly higher in men than in women. Age
      standardized mortalities of cancers of the esophagus, stomach, leukemia, female
      nasopharynx, female bladder, liver, and bone decreased especially after the
      1990s, those of the colon & rectum, kidney, prostate, pancreas, breast,
      gallbladder, and ovary increased significantly. Lung cancer, breast cancer,
      colorectal cancer, and pancreas cancer in women and lung cancer, colorectal
      cancer, prostate cancer, and stomach cancer in men will be the leading causes of
      cancer death in 2025-2029. Cancer-caused life loss kept increasing since 2000.
      Conclusively, cancers associated with pollutions and infection decreased,
      especially after the 1990s, while those related to metabolic syndrome increased.
      These trends are related to closedown of polluted industries in the 1980s and
      lifestyle changes.

PMID- 29190932
TI  - Multigene methylation analysis of enriched circulating tumor cells associates
      with poor progression-free survival in metastatic breast cancer patients.
AB  - Blood-based biomarkers such as circulating tumor cells (CTCs) provide dynamic
      real-time assessment of molecular tumor characteristics beyond the primary tumor.
      The aim of this study was to evaluate the feasibility of a size-based microfilter
      to assess multigene methylation analysis of enriched CTCs in a prospective proof
      of principle study. We examined the quantitative methylation status of nine genes
      (AKR1B1, BMP6, CST6, HOXB4, HIST1H3C, ITIH5, NEUROD1, RASSF1, SOX17) in enriched
      CTCs from metastatic breast cancer patients. Feasibility and clinical performance
      testing were assessed in a test set consisting of 37 patients and 25 healthy
      controls. With established cut-off values from the healthy control group,
      methylation of enriched CTCs was detected in at least one gene in 18/37 patients
      (48.6%), while 97.8% of all control samples were unmethylated. Patients with CTCs
      unmethylated for CST6, ITIH5, or RASSF1 showed significantly longer PFS compared
      to patients with corresponding enriched methylated CTCs. This proof-of-principle
      study shows the feasibility of a size-based microfilter to enrich and analyze
      multigene methylation profile of CTCs from metastatic breast cancer patients. For
      the first time, we report that multigene methylation analysis of enriched CTCs
      provides prognostic information in metastatic breast cancer patients.

PMID- 29190933
TI  - The anticipating value of PLK1 for diagnosis, progress and prognosis and its
      prospective mechanism in gastric cancer: a comprehensive investigation based on
      high-throughput data and immunohistochemical validation.
AB  - Polo-like kinase 1 (PLK1) is a multi-functional protein and its aberrant
      expression is a driver of cancerous transformation and progression. To increase
      our understanding of the clinical value and potential molecular mechanism of PLK1
      in gastric cancer (GC), we performed this comprehensive investigation. A total of
      25 datasets and 12 publications were finally incorporated. Additional
      immunohistochemistry was conducted to validate the expression pattern of PLK1 in
      GC. The pooled standard mean deviation (SMD) indicated that PLK1 mRNA was up
      regulated in GC (SMD=1.21, 95% CI: 0.65-1.77, P< 0.001). Similarly, the pooled
      odds ratio (OR) revealed that PLK1 protein was overexpressed in GC compared with
      normal gastric tissue (OR=12.12, 95% CI: 5.41-27.16, P<0.001). The area under the
      curve (AUC) of the summary receiver operating characteristic (SROC) curve was
      0.86. Furthermore, our results demonstrated that GC patients with PLK1
      overexpression were significantly associated with unfavorable overall survival
      (HR =1.54, 95% CI: 1.30-1.83, P<0.001), lymph node metastasis (OR = 1.78, 95% CI:
      1.13-2.80, P=0.013) and advanced TNM stage (OR=1.48, 95% CI: 1.02-2.15, P=0.038).
      Altogether, 100 similar genes were identified by Gene Expression Profiling
      Interactive Analysis (GEPIA) and further with gene-set enrichment analysis. These
      genes were related to gene ontology (GO) terms and Kyoto Encyclopedia of Genes
      and Genomes (KEGG) pathways relevant to the cell cycle. Gene set enrichment
      analysis (GSEA) indicated that PLK1 is associated with various cancer-related
      pathways. Collectively, this study suggests that PLK1 overexpression could play
      vital roles in the carcinogenesis and deterioration of GC via regulating tumor
      related pathways.

PMID- 29190934
TI  - Red blood cell distribution width as a predictor of survival in nasal-type,
      extranodal natural killer/T-cell lymphoma.
AB  - We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell
      lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer
      Hospital, in order to evaluate the relationship between disease outcomes,
      demographic and clinical factors, and red blood cell distribution width (RDW). C
      index, fisher's exact test, univariate analysis, and cox regression analysis were
      applied. The median age of patients was 44 years and 134 (70%) were men. The
      cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW<=46.2 fL
      had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs.
      63.1%; P=0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P=0.004)
      than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW
      is an independent adverse predictor of OS (P=0.021, HR=2.04). RDW is an
      independent predictor of survival outcomes in ENKTL, which we found to be
      superior to both the prognostic index of natural killer lymphoma (PINK) and the
      Korean Prognostic Index (KPI) in discriminating patients with different outcomes
      in low-risk and high-risk groups (all P < 0.05). The new models combining RDW
      with the International Prognostic Index (IPI), KPI, and PINK showed more powerful
      prognostic value than corresponding original models. RDW represents an easily
      available and inexpensive marker for risk stratification in patients with ENKTL
      treated with radiotherapy-based treatment. Further prospective studies are
      warranted to confirm the prognostic value of RDW in ENKTL.

PMID- 29190935
TI  - Reduced expression of chemerin is associated with poor clinical outcome in acute
      myeloid leukemia.
AB  - Chemerin is dysregulation in numerous solid cancers. However, only little is
      known about the role of chemerin in acute myeloid leukemia (AML). In this study,
      we aimed to investigate the expression and clinical significance of recently
      described chemerin in acute myeloid leukemia (AML). The expression of chemerin in
      149 patients with de novo AML and 35 normal controls was quantified by Real-time
      quantitative PCR (RQ-PCR). Chemerin was down-expressed in AML compared with
      controls (P=0.042). A receiver operating characteristic (ROC) curve revealed that
      chemerin expression could differentiate patients with AML from control subjects
      (AUC=0.611, 95% CI: 0.490-0.732; P=0.042) respectively. The cohort of AML
      patients was divided into two groups according to the cut-off value of 0.0826
      (79% sensitivity and 54% specificity, respectively). In addition, the AML
      patients with low chemerin expression had significantly shorter overall survival
      (OS) than those with high chemerin expression (P=0.049). Moreover, multivariate
      survival analysis confirmed that chemerin was an independent prognostic factor
      for AML patients. In conclusion, downregulation of chemerin might be a useful
      diagnostic and prognostic factor for AML patients.

PMID- 29190936
TI  - MiR-145 inhibits the epithelial-to-mesenchymal transition via targeting ADAM19 in
      human glioblastoma.
AB  - In recent years, increasing studies demonstrated that miR-145 plays a tumor
      suppressor role in many human cancers. In the present study, we evaluated the
      expression of miR-145 and A Disintegrin and Metalloproteinase 19 (ADAM19) in
      glioblastoma multiforme (GBM) tissues and cells. Furthermore, we investigated the
      mechanisms underlying miR-145/ADAM19-induced GBM biology. Here, we found that miR
      145 expression was down-regulated, while ADAM19 expression was up-regulated in
      GBM tissues and cells. Moreover, miR-145 mimics repressed U87 and U251 cell
      proliferation, migration and invasion. miR-145 mimics also inhibited the
      epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Mechanically,
      the 3' untranslated region (3'-UTR) of ADAM19 mRNA was a direct target for miR
      145. In addition, ADAM19 over-expression also partially abrogated miR-145
      inhibited EMT. In conclusion, this work suggested that high miR-145 expression
      inhibited EMT of GBM cells by targeting ADAM19. Thus miR-145/ADAM19 can be
      suggested as a novel target for GBM patients.

PMID- 29190937
TI  - 18F-fluorodeoxyglucose positron emission tomography-computed tomography as a
      screening tool for second primary cancers in cancer patients.
AB  - Background: We performed a meta-analysis to evaluate the value of 18F
      fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET
      CT) for the detection of second primary cancers in cancer patients. Results: This
      present study analyzed a total of 6 selected studies (1374 patients). The
      sensitivity and specificity of PET-CT were 0.84 (95% confidence interval [CI] =
      0.66 to 0.93), and 0.98 (95% CI = 0.97 to 0.98). Area under the curve was 0.98
      (95% CI = 0.96 to 0.99). Methods: Studies were systematically searched for
      relevant PET-CT original articles in the MEDLINE and EMBASE databases. We
      calculated the pooled sensitivity, specificity, and likelihood ratios for 18FDG
      PET-CT. We also constructed the summary receiver-operating characteristic curve
      for 18FDG PET-CT. Conclusions: 18FDG PET-CT has high sensitivity and specificity
      for the detection of second primary cancers in cancer patients.

PMID- 29190938
TI  - Enhanced killing of HepG2 during cryosurgery with Fe3O4-nanoparticle improved
      intracellular ice formation and cell dehydration.
AB  - Cryosurgery is a minimally invasive treatment that utilize extreme low
      temperatures to destroy abnormal tissues. The clinical monitoring methods for
      cryosurgery are almost based on the visualization of the iceball. However, for a
      normal cryosurgery process, the effective killing region is always smaller than
      the iceball. As a result, the end of the cryosurgery process can only be judged
      by the surgeons according to their experience. The subjective judgement is one of
      the main reasons for poor estimation of tumor ablation, and it sparks high
      probability of recurrence and metastasis associate with cryosurgery. Being
      different from the previous optimization studies, we develop a novel approach
      with the aid of nanoparticles to enlarge the effective killing region of entire
      iceball, and thus it greatly decrease the difficulty of precise judgement of the
      cryosurgery only by applying the common clinical imaging methods. To verify this
      approach, both the experiments on a tissue-scale phantom with embedded living
      HepG2 cells in agarose and on a cell-scale cryo-microscopic freeze-thaw stage are
      performed. The results indicate that the introduction of the self-synthesized
      Fe3O4 nanoparticles significantly improved cell killing in the cryosurgery and
      the range of killing is extended to the entire iceball. The potential mechanism
      is further revealed by the cryo-microscopic experiments, which verifies the
      presence of Fe3O4 nanoparticles can significantly enhance the probability of
      intracellular ice formation and the cell dehydration during freezing hence it
      promote precise killing of the cells. These findings may further promote the
      widespread clinical application of modern cryosurgery.

PMID- 29190939
TI  - Early antagonism of cerebral high mobility group box-1 protein is benefit for
      sepsis induced brain injury.
AB  - Sepsis induced brain injury acts as an acute complication and accounts for
      deterioration and high mortality rate of septic condition. HMGB1 is a late
      inflammatory mediator that plays a critical role in brain dysfunction and
      diseases. However, the role of HMGB1 in sepsis induced brain dysfunction remains
      intricate. The current study investigated the effect of HMGB1 on brain injury in
      septic mice model with intracerebroventricular injection of BoxA (a specific
      antagonist of HMGB1). The expression of HMGB1, morphological changes of brain
      tissues, apoptosis of brain cells, and alteration of behavior were determined.
      The expressions of HMGB1 in cortex, hippocampus, and striatum were significantly
      enhanced in the sepsis group when compared with the sham group. In septic
      conditions, brain tissues showed significant abnormalities in tissue structure,
      and increased apoptosis of brain cells which was caspase-3 dependent. Septic mice
      showed suppression of locomotor activity and impairment of memory and learning.
      Neutralizing brain HMGB1 significantly improved brain injury and apoptosis of
      brain cells, and further ameliorated disturbed locomotor activities and damaged
      memory and learning. However, no significant improvement of survival rate was
      seen after inhibiting central HMGB1. These results reveal that HMGB1 is a
      potential target for ameliorating sepsis induced brain injury with early
      antagonizing.

PMID- 29190940
TI  - Elevation of MAP17 enhances the malignant behavior of cells via the Akt/mTOR
      pathway in hepatocellular carcinoma.
AB  - MAP17, a small non-glycosylated membrane protein, was significantly up-regulated
      in hepatocellular carcinoma (HCC) tissues in our previous genome-wide microarray
      analysis. In this study, quantitative real-time RT-PCR and immunohistochemistry
      were applied to examine MAP17 mRNA and protein expression in primary HCC and
      matched peritumoral tissues. The disease-free survival (DFS) and overall survival
      (OS) was estimated using the Kaplan-Meier analysis. The expression of MAP17 was
      significantly higher in HCC tissues compared to the paired peritumoral tissues at
      both mRNA and protein levels. High MAP17 expression was positively correlated
      with gender, distant metastasis, early recurrence (<= 2 year), and serum alpha
      fetoprotein (all p < 0.05). Kaplan-Meier analysis showed that the DFS (p = 0.004)
      and OS (p = 0.013) in HCC patients with elevated expression of MAP17 were much
      worse than that in the low expression subgroup. High level of MAP17 was also
      significantly associated with a high probability of HCC early recurrence after
      surgical resection (p = 0.005). Cox regression analysis indicated MAP17 was an
      independent prognostic factor for DFS (HR, 1.710; 95% CI, 1.156-2.449, p = 0.012)
      and OS (HR, 1.743; 95% CI, 1.152-2.639, p = 0.009) in HCC. Silencing MAP17
      significantly inhibited the proliferation, invasion and migration of HCC cells in
      vitro, and decreased the expression levels of Akt, p-Akt (Ser473), mTOR, p-mTOR
      (Ser2448) and MMP-9. Suggesting MAP17 was a novel diagnostic and prognostic
      biomarker for HCC patients and promoted HCC cell proliferation, invasion and
      migration via the Akt/mTOR pathway.

PMID- 29190941
TI  - Associations between novel genetic variants in the promoter region of MALAT1 and
      risk of colorectal cancer.
AB  - The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known
      long non-coding RNA, is involved in pathogenesis and progress of multiple tumors.
      However, no study has been performed to investigate the relationship between the
      genetic variants in promoter region of MALAT1 and colorectal cancer risk. In this
      study, we conducted a two-stage case-control study to evaluate whether MALAT1
      genetic variants were associated with colorectal cancer risk. We identified that
      a single nucleotide polymorphism (SNP) rs1194338 was significantly associated
      with the decreased colorectal cancer risk with an odds ratio (OR) of 0.70 [95%
      confidence interval (CI) = 0.49-0.99] in the combined stage. The subsequently
      stratified analyses showed that the protective effect of rs1194338 was more
      pronounced in several subgroups. Furthermore, gene expression profiling analysis
      revealed overexpression of MALAT1 mRNA in colorectal cancer tissue compared with
      normal controls. Confirmation studies with large sample size and further
      mechanistic investigations into the function of MALAT1 and its genetic variants
      are warranted to advance our understanding of their roles in colorectal
      carcinogenesis, and to aid in the development of novel and targeted therapeutic
      strategies.

PMID- 29190942
TI  - Clinical predictors of intracranial injuries on CT in infants younger than 2
      years old with mild traumatic brain injury.
AB  - Purpose: Mild traumatic brain injury (TBI) is common in children. The aim of this
      study was to identify clinical predictors of intracranial injuries on computed
      tomography (CT) in infants younger than 2 years old with mild TBI, which allow
      reducing number of imaging. Results: Of 214 enrolled infants with complete data,
      30 (5.8%) sustained intracranial injuries. Younger age in months, severe injury
      mechanism and scalp hematomas were associated with traumatic intracranial
      injuries on CT. 71 had scalp hematomas and 143 had no scalp hematoma. Within
      infants with scalp hematomas, 26 sustained intracranial injuries and 45 presented
      normal. Intracranial injuries were significantly correlated with larger scalp
      hematomas and different scalp hematoma locations. Logistic regression analysis
      showed that scalp hematoma and mechanism of injury in infants younger than 2
      years old with mild TBI was related to intracranial injuries (hazard
      ratio=38.291, P=0.0001; hazard ratio=0.174, P=0.001). In subgroup of mild TBI
      infants with scalp hematomas, logistic regression analysis showed age, scalp
      hematoma size and mechanism of injury were independently associated with
      intracranial injuries (hazard ratio=0.299, P=0.032; hazard ratio=5.272, P=0.006;
      hazard ratio=0.312, P=0.030). Methods: Between 2014 and 2016, we retrospectively
      enrolled infants <2 years old with mild TBI. Data recorded included age, sex,
      mechanism of head injury, size and location of scalp hematoma, fracture and
      intracranial injuries on CT. Conclusion: The characteristics of scalp hematomas
      and mechanism of injury were associated with intracranial injuries. These factors
      should be considered when making decisions on radiologic examinations of infants
      < 2 years old with mild TBI and alternative procedures, which do not involve
      ionizing radiation, should be used if appropriate.

PMID- 29190943
TI  - Neuroprotective effects of bajijiasu against cognitive impairment induced by
      amyloid-beta in APP/PS1 mice.
AB  - Alzheimer's disease (AD) is a progressive neurological degenerative disease. The
      main clinical manifestations of AD include progressive cognitive impairment and
      alteration of personality. Senile plaques, neuroinflammation, and destruction of
      synapse structure stability are the main pathological features of AD.
      Bajijiasu(BJJS) is extracted from Morinda Officinalis, a Chinese herb. In this
      study, we explored the effect of BJJS on AD from many aspects in
      APPswe/PSEN1DeltaE9 (APP/PS1) double transgenic mice. The Morris water maze and
      novel object recognition tests results showed that BJJS could significantly
      improve the learning and memory abilities in APP/PS1 mice. BJJS treatment
      increased the level of insulin degradation enzyme (IDE) and neprilysin (NEP) and
      decreased the level of beta-site app cleaving enzyme 1(BACE1) in the brain of
      APP/PS1 mice. BJJS-treated APP/PS1 mice appeared to have reductions of Abeta
      deposition and senile plaques, and showed higher levels of neurotrophic factors
      in the brain. We also found that BJJS had an inhibitory function on
      neuroinflammation in APP/PS1 mice. In addition, the synapse structure relevant
      proteins were elevated in the brain of BJJS-treated APP/PS1 mice. The present
      results indicated that BJJS could attenuate cognitive impairment via ameliorating
      the AD-related pathological alterations in APP/PS1 mice. These findings suggest
      that BJJS may be a potential therapeutic strategy in Alzheimer's disease.

PMID- 29190944
TI  - Alteration of exosomes secreted from renal tubular epithelial cells exposed to
      high-concentration oxalate.
AB  - Oxalate (Ox) is a metabolic end product that is produced by the kidneys and is
      associated with several pathological conditions. The accumulation of oxalate in
      the body is one of the factors that lead to calcium oxalate kidney stones. To
      simulate the high-concentration Ox environment in vivo, we established an in
      vitro model of high Ox using renal tubular epithelial (HK-2) cells. Cell
      viability and proliferation were assessed to evaluate the effects of various
      concentrations (0, 0.25, 0.5, 1, 2, 4, 5, 8 and 10Mm) of Ox on HK-2 cells to
      select the optimum concentration and time to extract the exosomes. Treatment with
      0, 1, or 2 mM Ox altered the morphology and secretion capacity of exosomes. As
      the concentration of Ox increased, peak and mean particle size decreased, but
      exosomes particle concentration, exosome RNA, and exosome protein increased.
      Size, distribution, and rate of secretion, as well as RNA and protein content,
      differed among extracellular vesicle subtypes. Furthermore, the three subtypes of
      exosomes delivered different signal factors in the microenvironment. We therefore
      speculated that three subtypes of exosomes may play differing roles in
      intercellular signal communication and the formation of CaOx kidney stones.

PMID- 29190945
TI  - Serum ferritin and primary lung cancer.
AB  - Existing research yields conflicting results regarding the relation between iron
      deficiency and high serum ferritin (SF) levels in primary lung cancer patients.
      We investigated the concentrations of SF, hemoglobin (Hb) and transferrin (TRF)
      in 569 male primary lung cancer patients and 252 female primary lung cancer
      patients. We grouped the subjects according to gender, smoking status, menopausal
      status, pathological type, stage, and TNM stage. The levels of SF and TRF were
      correlated with T stage in male patients (p<0.01). The levels of SF and TRF were
      correlated with menopausal status in female patients (p<0.01). Hb was correlated
      with smoking status, pathological type, stage, and TNM stages in male
      patients(p<0.01), but in female patients, Hb was not correlated with these
      grouping factors(p>0.05). The levels of SF may be regulated by different
      mechanisms and may be of different physiological significance in different
      populations.

PMID- 29190946
TI  - beta2GPI exerts an anti-obesity effect in female mice by inhibiting lipogenesis
      and promoting lipolysis.
AB  - In humans, males compared to females have increased visceral adipose tissue which
      contributes to their increased risk of early death. Mice display analogous sexual
      diamorphism whereby females are protected from weight gain when fed a high fat
      diet compared to males. A role has recently been reported for beta2-glycoprotein
      I, an abundant plasma protein, in healthy leanness in humans. In this study we
      investigated the role of beta2-glycoprotein I in fat metabolism in male and
      female mice fed a normal chow or high fat diet. We have made a number of novel
      insights into factors contributing to sexual diamorphism in obesity. Female wild
      type mice are protected from obesity when fed a high fat diet due to down
      regulation of lipogenesis in the visceral adipose tissues. This down regulation
      is due to beta2-glycoprotein I as female mice deficient in this protein have
      increased levels of lipogenesis enzymes in their visceral adipose tissues with an
      accompanying increase in weight compared to female wild type controls.
      Understanding female specific regulators of obesity may lead to sex specific anti
      obesity therapies to address this major health problem.

PMID- 29190947
TI  - Thioredoxin system-mediated regulation of mutant Kras associated pancreatic
      neoplasia and cancer.
AB  - Peroxiredoxin-1 (Prdx1), a member of the thioredoxin (Txn) system, is
      overexpressed and correlates with poor prognosis in pancreatic cancer patients
      and can suppress Kras signaling through redox-mediated inhibition of ERK and AKT
      in lung and breast cancer. Its redox function is maintained by Txn and
      sulfiredoxin (Srxn), and its tumor promoting functions are activated by post
      translational modification. We studied the role of the Txn system in pancreatic
      neoplasia and cancer by determining how it regulates the phosphorylation of Kras
      effectors and by determining its association with patient survival. We found that
      elevated Prdx1 nuclear localization significantly correlated with better patient
      survival. Our data also demonstrate that the expression of the Txn system is
      dysregulated, with elevated Prdx1 expression and significantly decreased Txn and
      Srxn expression in pancreatic lesions of targeted mutant Kras mouse models. This
      correlated with distinct differences in the interconversion of Prdx1 oligomers
      that affect its ability to regulate ERK and AKT phosphorylation. Our data also
      suggest that Prdx1 post-translational modification and oligomerization suppress
      Prdx1 mediated redox regulation of ERK phosphorylation. We observed distinct
      differences in Txn expression and in the ability of pTyr-Prdx1 to bind to pERK in
      a PanIN model of pancreatic neoplasia as compared to an IPMN model, indicating a
      distinct difference in the function of post-translationally modified Prdx1 in
      cells with less Txn expression. Modified Txn system function and post
      translational regulation may therefore play a significant role in pancreatic
      tumorigenesis by altering Kras effector phosphorylation and inhibiting the tumor
      suppressive redox functions of Prdx1.

PMID- 29190948
TI  - Enhanced antitumor efficacy and reduced toxicity of Abnormal Savda Munziq on
      tumor bearing mice treated with chemotherapy.
AB  - Previous research has demonstrated the anti-tumor properties of Abnormal Savda
      Munziq (ASMq), a traditional Uyghur compound herbal medicine. The effects of ASMq
      on cervical carcinomas in U27 tumor-bearing mice is investigated, the effect of
      adding Fluorouracil (5-FU) is also assessed in this paper. The results
      demonstrate that ASMq and 5-FU significantly inhibited the proliferation of U27
      cells in a time-dependent and dose-dependent manner. Evaluating the interactions
      between ASMq and 5-FU on U27 cell growth yields a combination index (CI) < 1 in
      different time periods, suggesting a synergistic effect between the two drugs in
      vitro. Nuclear magnetic resonance (NMR) analysis demonstrates that ASMq can
      inhibit enhanced lipid metabolism in tumor mice, enhance the glutamine content,
      promote lymphocyte and macrophage proliferation, and increase tumor necrosis
      factor(TNF-alpha) and interleukin(IL) production, which can enhance the effect of
      5-FU on the inhibition of tumors. Also ASMq can reduce the content of ALT and AST
      in serum. Increased SOD, GSH-Px, and decreased the content of MDA in liver
      tissue. ASMq has a synergistic effect on liver and tumor pathology, as well as
      tumor inhibition rate. In addition, ASMq can also enhance the body's antioxidant
      capacity and improve the body's metabolism, and reduce 5-FU's toxic side effects.

PMID- 29190949
TI  - Association between PD-L1 expression combined with tumor-infiltrating lymphocytes
      and the prognosis of patients with advanced hypopharyngeal squamous cell
      carcinoma.
AB  - Limited information is available regarding the immune-related prognostic factors
      of patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). The
      expression of programmed cell death-ligand 1 (PD-L1) in tumor cells contributes
      to a mechanism that allows cancer cells to escape immune surveillance. We
      investigated whether PD-L1 or human leukocyte antigen (HLA) class I expression in
      tumor cells and the tumor-infiltrating lymphocyte (TIL) density were associated
      with the tumor response to neoadjuvant chemotherapy (NAC) and survival in
      patients with advanced HPSCC. We retrospectively reviewed 83 consecutive patients
      with stage III or IV HPSCC who received NAC. We evaluated PD-L1 and HLA class I
      expression and TIL density using immunohistochemistry. Univariate and
      multivariate analyses demonstrated that CD8+ TIL density was an independent and
      significant predictive factor for the response to NAC, progression-free survival
      (PFS) and overall survival (OS), whereas PD-L1 or HLA class I expression did not
      significantly correlate. The subgroup analysis revealed that a higher CD8+ TIL
      density without detectable PD-L1 expression tended to be associated with longer
      patient survival. These results suggest that PD-L1 expression levels combined
      with CD8+ TIL density may serve as a predictive biomarker for patients with stage
      III or IV HPSCC receiving NAC.

PMID- 29190950
TI  - Therapeutic response and long-term outcome of differentiated thyroid cancer with
      pulmonary metastases treated by radioiodine therapy.
AB  - Objective: To explore the therapeutic response (TR) and long-term outcomes of
      iodine-131 (I-131) treatment for patients with differentiated thyroid cancer and
      pulmonary metastases (DTC+PM), as well as the association between the assessment
      of TR and long-term outcomes. Methods: This retrospective study comprised 151
      DTC+PM patients. TR was evaluated by changes in serum levels of thyroglobulin,
      anatomic imaging and iodine uptake in pulmonary nodules; logistic regression was
      applied to identify predictors. Overall survival (OS) was calculated using the
      Kaplan-Meier method and predictive factors of outcome by multivariate analyses.
      Results: After I-131 treatment, 17 patients achieved a complete response, 71 a
      partial response, and 63 no response. Age, pulmonary nodule size, iodine
      concentration within PM, extra-PM, frequency and cumulative dose of I-131
      treatment were significant for TR. OS was 72.2% at 5, 55.2% at 10 and 51.3% at 15
      years. After adjustment for other factors, age, pulmonary nodule size, extra-PM,
      frequency and cumulative dose of I-131 treatment were significant. A significant
      difference of survival rate in patients with different TR group was observed.
      Conclusions: There was a supportive response and prognosis for I-131 treatment
      upon DTC+PM patients. Older patients and those with non-I-131-avid PM were more
      likely to have no response to I-131 treatment, and greater benefits could be
      achieved by patients who complete treatment. Long-term outcome was better in
      patients with age <45 years, pulmonary nodule size <2 cm, without extra-PM, and
      the frequency of iodine treatment >=5 times. The predictive power of the TR on
      long-term prognosis was favorable.

PMID- 29190951
TI  - Multi-omics analysis reveals that ornithine decarboxylase contributes to
      erlotinib resistance in pancreatic cancer cells.
AB  - Molecular and metabolic alterations in cancer cells are one of the leading causes
      of acquired resistance to chemotherapeutics. In this study, we explored an
      experimental strategy to identify which of these alterations can induce erlotinib
      resistance in human pancreatic cancer. Using genetically matched erlotinib
      sensitive (BxPC-3) and erlotinib-resistant (BxPC-3ER) pancreatic cancer cells, we
      conducted a multi-omics analysis of metabolomes and transcriptomes in these
      cells. Untargeted and targeted metabolomic analyses revealed significant changes
      in metabolic pathways involved in the regulation of polyamines, amino acids, and
      fatty acids. Further transcriptomic analysis identified that ornithine
      decarboxylase (ODC) and its major metabolite, putrescine, contribute to the
      acquisition of erlotinib resistance in BxPC-3ER cells. Notably, either
      pharmacological or genetic blockage of ODC was able to restore erlotinib
      sensitivity, and this could be rescued by treatment with exogenous putrescine in
      erlotinib-resistant BxPC-3ER cells. Moreover, using a panel of cancer cells we
      demonstrated that ODC expression levels in cancer cells are inversely correlated
      with sensitivity to chemotherapeutics. Taken together, our findings will begin to
      uncover mechanisms of acquired drug resistance and ultimately help to identify
      potential therapeutic markers in cancer.

PMID- 29190952
TI  - Verrucarin J inhibits ovarian cancer and targets cancer stem cells.
AB  - Ovarian Cancer is the fifth leading cause of death among women from cancer.
      Cancer stem cells are a small population of cells present in cancer and the cause
      of chemoresistance and recurrence of cancer. We tested a new compound "Verrucarin
      J (VJ)", a metabolite of the Myrothecium fungus family, and showed that VJ
      significantly inhibits cell proliferation of both cisplatin-sensitive (A2780 and
      OVCAR5) and cisplatin-resistant (A2780/CP70) cell lines in a dose- and time
      dependent manner with IC50 value of approximately 10 nM after 48 h of treatment.
      VJ was found to induce apoptosis, DNA damage, and generation of reactive oxygen
      species (ROS). Treatment of A2780 cells with VJ resulted in a significant
      suppression of expression of CSCs markers including ALDH1, LGR5, NANOG and OCT4
      in a dose-dependent manner, elimination of ALDH1+ CSC population and inhibition
      of expression of Notch1 and Wnt1 signaling pathways. Our study also showed that
      VJ inhibited the tumorigenic potential (spheroid formation on ultralow attachment
      plates) of isolated ALDH1+ CSCs in vitro and tumor growth and metastasis in vivo.
      VJ resulted downregulation of expression of securin an "oncogene" involved in
      tumor growth and progression, indicating that securin may serve as a downstream
      signaling gene to mediate antitumor effects of VJ.

PMID- 29190953
TI  - Distribution pattern of tumor associated macrophages predicts the prognosis of
      gastric cancer.
AB  - Purpose: As mayor biomarkers in tumor microenvironment (TME), tumor associated
      macrophages (TAMs) of gastric cancer (GC) still needs further studies in terms of
      the number and distribution pattern. Methods: Herein, tissue microarrays (TMA)
      incorporating 494 GC surgical samples in duplicate were stained for TAMs
      infiltration analysis. TAMs number was counted according to the locations,
      including infiltrating macrophages in cancer nest (MC), in invasive front (MF)
      and in stroma (MS). Correlations between TAMs number, distribution pattern and
      clinic-pathological features and survival analyses were performed. Results:
      Infiltrating macrophages number in GC tissues was much higher than that in
      peritumoral tissues. TAMs number was not significantly correlated with the
      overall survival (OS). TAMs distribution pattern could be categorized into MC or
      MF/MS dominant pattern, and correlated with histological grade (P =0.001). The
      median OS of MF/MS dominant pattern (22.1, 95%CI: 23.5-28.9) was significantly
      shorter than that of MC dominant pattern (25.6, 95%CI: 28.5-35.6) (P =0.002). By
      receiver operating characteristic curve (ROC) analysis, the predictive value of
      TAMs distribution pattern was superior to histological grade and pM stage, but
      inferior to pN and TNM stage. Conclusions: TAMs distribution pattern could be an
      independent prognostic factor for the OS of GC patients, and patients with MF/MS
      dominant pattern had worse outcomes.

PMID- 29190954
TI  - Cyclooxygenase-2 mediated synergistic effect of ursolic acid in combination with
      paclitaxel against human gastric carcinoma.
AB  - Ursolic acid (UA) induces apoptosis in gastric cancer cells by inhibiting
      cyclooxygenase-2 (COX-2). Paclitaxel (PTX) is an important chemotherapy agent
      used to treat solid tumors. We evaluated the in vitro antitumor activity of UA in
      combination with PTX against gastric cancer cells and investigated the mechanisms
      underlying the combined effects. A cytotoxicity test and flow cytometry were
      utilized to study the effects of UA and PTX on proliferation and apoptosis,
      respectively. To further elucidate the mechanism, Western blot analysis was used
      to assess changes in the expression of a series of related proteins, including
      COX-2, proliferating cell nuclear antigen (PCNA), Bcl-2, and Bax. UA and PTX dose
      and time-dependently inhibited BGC-823 and SGC-7901 gastric cancer cell
      proliferation. Combined delivery of UA and PTX synergistically reduced cell
      proliferation and induced apoptosis in these cells by lowering COX-2, PCNA, and
      Bcl-2 expression and by increasing Bax expression. These results indicate that
      the synergistic inhibition of proliferation and induction of apoptosis by UA and
      PTX may be induced by reducing COX-2 expression in gastric cancer cells.

PMID- 29190955
TI  - Concurrent administration of trastuzumab and anthracyclines as adjuvant regimen
      for HER2-positive breast cancer: a randomised controlled trial.
AB  - Background: The regimen of concurrent administration of trastuzumab and
      anthracyclines in the adjuvant treatment of breast cancer has never been
      evaluated prospectively for fear of cardiac toxicity. Methods: Patients with HER2
      positive operable breast cancer were randomised to receive adjuvant treatment
      with concurrent or sequential administration of trastuzumab and anthracyclines.
      Cardiac monitoring was scheduled at baseline and every 3 months after the first
      dose of trastuzumab. The primary study endpoint was cardiac safety. Secondary
      endpoints were disease-free and overall survival. Results: From 2011 to 2014, 201
      participants were enrolled and randomised. The median follow-up time was 42
      months. Nineteen patients (19.4%) in the concurrent group and 22 patients (22.4%)
      in the sequential group met the criteria for cardiac events with non-significant
      difference (P=0.598). There was no difference in the mean LVEF between the two
      groups at the baseline and at 3, 6, 9, 12, and 24 months after the first dose of
      trastuzumab. No case of congestive heart failure or cardiac death occurred. The
      differences between the efficacies of the two regimens, defined by disease-free
      or overall survival, were not significant. Conclusions: Concurrent administration
      of trastuzumab and anthracyclines is a safe adjuvant regimen and it provides
      evidence for further clinical trials.

PMID- 29190956
TI  - Peroxiredoxin 3 maintains the survival of endometrial cancer stem cells by
      regulating oxidative stress.
AB  - Cancer stem cell (CSC)-targeted therapy could reduce tumor growth, recurrence,
      and metastasis in endometrial cancer (EC). The mitochondria of CSCs have been
      recently found to be an important target for cancer treatment, but the
      mitochondrial features of CSCs and their regulators, which maintain mitochondrial
      function, remain unclear. Here, we investigated the mitochondrial properties of
      CSCs, and identified specific targets for eliminating CSCs in EC. We found that
      endometrial CSCs displayed higher mitochondrial membrane potential, Ca2+,
      reactive oxygen species, ATP levels, and oxygen consumption rates than non-CSCs.
      Further, we also verified that mitochondrial peroxiredoxin 3 (Prx3) was
      upregulated, and that it contributed to the survival of CSCs in EC. The knockdown
      of the Prx3 gene resulted not only in decreased sphere formation, but also
      reduced the viability of endometrial CSCs, by causing mitochondrial dysfunction.
      Furthermore, we found that the forkhead box protein M1 (FoxM1), an important
      transcriptional factor, is overexpressed in patients with EC. FoxM1 expression
      correlates with elevated Prx3 expression levels, in agreement with the
      tumorigenic ability of Prx3 in endometrial CSCs. Taken together, our findings
      indicate that human endometrial CSCs have enhanced mitochondrial function
      compared to that of endometrial tumor cells. Endometrial CSCs show increased
      expression of the mitochondrial Prx3, which is required for the maintenance of
      mitochondrial function and survival, and is induced by FoxM1. Based on our
      findings, we believe that these proteins might represent valuable therapeutic
      targets and could provide new insights into the development of new therapeutic
      strategies for patients with endometrial cancer.

PMID- 29190957
TI  - MicroRNA-30c-5p ameliorates hypoxia-reoxygenation-induced tubular epithelial cell
      injury via HIF1alpha stabilization by targeting SOCS3.
AB  - The cellular hypoxia-reoxygenation (H/R) model is an ideal method to study
      ischemia-reperfusion injury, which is associated with high mortality. The role of
      microRNA-30c-5p (miR-30c-5p) in the H/R epithelial cell model remains unknown. In
      the current study, we observed a significant reduction in apoptosis when miR-30c
      5p was up-regulated. We also found decreased levels of C-caspase-3 (C-CASP3) and
      Bcl-2-associated X (BAX) proteins and increased levels of B-cell lymphoma-2
      (BCL2). Epidermal growth factor receptor (EGFR) showed similar results. Down
      regulating miR-30c-5p increased the levels of apoptosis and C-CASP3 and BAX
      expression; additionally, cell proliferation was inhibited. Hypoxia-inducible
      factor 1alpha (HIF1alpha) protein expression levels were up-regulated in response
      to up-regulation of miR-30c-5p expression. The anti-apoptotic and proliferative
      effects of miR-30c-5p decreased significantly after the HIF1alpha protein levels
      were knocked down. Using a luciferase reporter assay, we confirmed that miR-30c
      5p targets suppressor of cytokine signaling-3 (SOCS3). HIF1alpha levels increased
      when SOCS3 was blocked. Our data show that SOCS3 expression enhances apoptosis in
      the H/R model. In conclusion, up-regulating miR-30c-5p protects cells from H/R 
      induced apoptosis and induces cell proliferation; furthermore, HIF1alpha markedly
      contributes to this protective effect. MiR-30c-5p stabilizes HIF1alpha expression
      by targeting SOCS3 to achieve anti-apoptotic and proliferative effects.

PMID- 29190958
TI  - LncRNA BCAR4 promotes colon cancer progression via activating Wnt/beta-catenin
      signaling.
AB  - BCAR4 (Breast Cancer Anti-Estrogen Resistance 4) is a long noncoding RNA that was
      identified as an oncogene in breast cancer. In our research, we found that the
      expression level of BCAR4 was upregulated in colon cancer tissues compared to
      paired normal tissues. What's more, higher BCAR4 expression was correlated with
      lower survival rate in patients with colon cancer. Mechanistically, we showed
      that BCAR4 activated Wnt/beta-catenin signaling in colon cancer by protecting
      beta-catenin from degradation. We also showed that BCAR4 overexpression promoted
      cell proliferation and migration in colon cancer. However, silencing BCAR4
      inhibited cell growth and promoted apoptosis. Besides, BCAR4 knockdown decreased
      tumor growth in vivo. These findings indicate that BCAR4 facilitated colon cancer
      progression by enhancing cell proliferation and inhibiting apoptosis via
      BCAR4/beta-catenin axis. BCAR4 may be a useful new target for treatment of
      patients with colon cancer.

PMID- 29190959
TI  - Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms.
AB  - Background and aims: Determine the effect of AMPK activation and inhibition on
      the development of AAA (abdominal aortic aneurysm). Methods: AAA was induced in
      ApoE-/- mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4
      carboxamide-1-beta-d-ribofuranoside) was used as AMPK activator and Compound C
      was used as AMPK inhibitor. We further investigate the effect of metformin, a
      widely used anti-diabetic drug which could activate AMPK signal pathway, on the
      pathogenesis of aneurysm. Results: Phospho-AMPK level was significantly decreased
      in AAA tissue compared with control aortas. AICAR significantly reduced the
      incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR
      also alleviated macrophage infiltration and neovascularity in Ang II infusion
      model at day 28. The expression of pro-inflammatory factors, angiogenic factors
      and the activity of MMPs were also alleviated by AICAR during AAA induction. On
      the other hand, Compound C treatment did not exert obvious protective effect.
      AMPK activation may inhibit the activation of nuclear factor-kappaB (NF-kappaB)
      and signal transducer and activator of transcription-3 (STAT-3) during AAA
      induction. Administration of metformin also activated AMPK signal pathway and
      retarded AAA progression in Ang II infusion model. Conclusions: Activation of
      AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may
      be a promising approach to the treatment of AAA.

PMID- 29190960
TI  - Interleukin-32alpha promotes the proliferation of multiple myeloma cells by
      inducing production of IL-6 in bone marrow stromal cells.
AB  - Multiple myeloma (MM) is a malignant plasma disease closely associated with
      inflammation. In MM bone marrow microenvironment, bone marrow stromal cells
      (BMSCs) are the primary source of interleukin-6 (IL-6) secretion, which promotes
      the proliferation and progression of MM cells. However, it is still unknown how
      the microenvironment stimulates BMSCs to secrete IL-6. Interleukin-32 (IL-32) is
      a newly identified pro-inflammatory factor. It was reported that in solid tumors,
      IL-32 induces changes in other inflammatory factors including IL-6, IL-10, and
      TNF-alpha. The aim of this study was to investigate the expression of IL-32 and
      the role of IL-32 in the MM bone marrow microenvironment. Our data illustrate
      that MM patients have higher expression of IL-32 than healthy individuals in both
      bone marrow and peripheral blood. We used ELISA and qRT-PCR to find that
      malignant plasma cells are the primary source of IL-32 production in MM bone
      marrow. ELISA and Western blot analysis revealed that recombinant IL-32alpha
      induces production of IL-6 in BMSCs by activating NF-kappaB and STAT3 signaling
      pathways, konckdown of IL-32 receptor PR3 inhibit this process. Knockdown of IL
      32 by shRNA decreased the proliferation in MM cells that induced by BMSCs. In
      conclusion, IL-32 secreted from MM cells has paracrine effect to induce
      production of IL-6 in BMSCs, thus feedback to promote MM cells growth.

PMID- 29190961
TI  - Long noncoding RNA CCAT1 functions as a ceRNA to antagonize the effect of miR-410
      on the down-regulation of ITPKB in human HCT-116 and HCT-8 cells.
AB  - Colorectal cancer is one of the most common malignancies, which has seriously
      affected people's health. Abnormal expression of long non-coding RNAs and
      microRNAs are closely related to the process of occurrence, development, invasion
      and metastasis of colorectal cancer. However, the effect of lnc CCAT1 on human
      HCT-116/HCT-8 cells and its potential mechanism were investigated. In present
      study, differential expression of CCAT1, miR-410 and ITPKB were detected in colon
      cancer tissues and adjacent parts. Then the prediction programs were applied to
      predict the target genes of miR-410. The complementary bindings of miR-410 with
      lnc CCAT1 and ITPKB were assessed by luciferase assays. The interaction between
      LncRNA CCAT1 and miR-410 was analyzed. In addition, the mRNA and protein of ITPKB
      and apoptosis factors were examined in cells after miR-410 overexpression or
      silencing. Meanwhile, MTT and flow cytometer were used to detect the cells
      proliferation and apoptosis level. Results showed that CCAT1 and miR-410 were up
      regulated in colon cancer tissues, but ITPKB was down-regulated. Lnc CCAT1 and
      ITPKB were predicted to be the targets of miR-410 and the prediction were
      verified by luciferase assays. The expression of lnc CCAT1 and ITPKB were
      inhibited by miR-410 in human HCT-116/HCT-8 cells. Meanwhile, lnc CCAT1 could
      lead to a decrease of miR-410. Furthermore, miR-410 overexpression could promote
      cell proliferation and reduce apoptosis. In summary, these data demonstrated that
      miR-410 could promote cell proliferation and reduce apoptosis by inhibiting ITPKB
      expression and the expression of lnc CCAT1 antagonized the effect of miR-410.

PMID- 29190962
TI  - Wu-tou decoction attenuates neuropathic pain via suppressing spinal astrocytic IL
      1R1/TRAF6/JNK signaling.
AB  - Neuropathic pain (NP) caused by nerve injuries continues to be an intractable
      challenge due to inadequate therapeutic strategies. Recent study demonstrated
      glia-induced neuro-inflammation in the spinal cord, especially the activation of
      astrocytes, plays an essential role in the development of NP, which opens new
      avenues for NP treatment. In this study, we explored the anti-hyperalgesia
      properties of Wu-tou decoction (WTD) and showed that WTD potently attenuates
      mechanical allodynia and heat hyperalgesia in lumbar 5 (L5) spinal nerve ligation
      (SNL)-induced NP without noticeable side effect or affecting basal pain
      perception of mice. Mechanistically, initial targets screening tests indicated
      WTD's analgesic action may be centrally mediated within the spinal cord, which
      further verified by its inhibitory actions on glia-releasing factors of IL-1beta,
      CCL2 and CXCL1. Meanwhile, WTD significantly reduced spinal IL-1R1, TRAF6
      expressions, p-JNK levels, and number of GFAP/IL-1R1, GFAP/TRAF6, GFAP/p-JNK
      positive astrocytes in the superficial lamina of spinal cord. Additionally, co
      administration of IL-1Ra increased the anti-hyperalgesia effects of WTD and
      further decreased CCL2 and CXCL1 expressions, while no synergistic effects were
      detected when TRAF6 or JNK inhibitors were co-administrated with WTD. Thus, our
      data suggested that the effective inhibition of spinal astrocytic IL
      1R1/TRAF6/JNK signaling (especially IL-1R1) contributes, at least in part, to
      WTD's anti-hyperalgesia action. It also indicates that WTD might be a promising
      candidate for the treatments of chronic pain, especially under NP-related
      neurological disorders.

PMID- 29190963
TI  - Inter- and intra-observer reproducibility of ADC measurements in esophageal
      carcinoma primary tumors.
AB  - The apparent diffuse coefficient (ADC) may correlate with the treatment response
      to chemotherapy/radiotherapy in solid tumors. Our aim was to determine the inter-
      and intra-observer reproducibility of ADC measurements in primary esophageal
      squamous cell carcinoma (ESCC). ADCs were blindly measured in 31 patients
      diagnosed with ESCC by two observers before treatment (pre-ADC) and after 5th
      fraction radiotherapy (intra-ADC) twice with a 2-week interval. The mean pre-ADC
      of primary tumors was 1.25+/-0.22 and 1.27+/-0.23 (in 10-3mm2/s) from observer A
      for measurements 1 and 2, respectively, and the intra-observer measurements were 
      0.02 bias vs. -0.13-0.09 limits of agreement. From observer B, the mean pre-ADC
      varied between 1.25+/-0.23 and 1.27+/-0.23 (in 10-3mm2/s) for measurements 1 and
      2, respectively, and intra-observer measurements were -0.02 bias vs. -0.17~0.16
      limits of agreement. The mean pre-ADC of primary tumors was 1.26+/-0.24 (in 10
      3mm2/s) from observers A and B, and inter-observer measurements were 0.01 bias
      vs. -0.09-0.09 limits of agreement, revealing a low inter-observer variance.
      Similar measurements of the intra-SD parameters showed that the pre- and intra
      ADC of primary tumors differed significantly. Thus ADC measurements may have
      sufficient inter-observer and intra-observer reproducibility to measure primary
      tumor responses to treatment, and the ADCs before and during treatment differed.

PMID- 29190965
TI  - Association between dose-volume parameters and acute bone marrow suppression in
      rectal cancer patients treated with concurrent chemoradiotherapy.
AB  - Concurrent chemoradiotherapy is one of the main treatments for rectal cancer.
      Bone marrow suppression is one of the critical factors that affect the progress
      of radiotherapy. We aimed to explore the association of incidence of acute bone
      marrow suppression with dose-volume parameters of pelvic bone marrow among rectal
      cancer patients with concurrent chemoradiotherapy. We retrospectively analyzed 50
      rectal cancer patients for multivariate logistic regression analyses. Three
      subdomains of pelvic bone marrow (PBM), bilateral ilium (IBM), lower pelvis
      (LPBM), and lumbosacral spine (LSBM) were assigned. The radiation dose-volume
      parameters from the three subdomains and the whole pelvis were evaluated.
      Compared to Grade 0-1 leukopenia patients, >=Grade 2 leukopenia patients
      exhibited significantly higher levels of IBM V20, V25, V35, mean dose (Dmean),
      LPBM V20, V25, V30, LSBM V15, PBM V15, V20, and PTV. The PBM V20 of >=Grade 2
      neutropenia patients was significantly higher than that of Grade 0-1 neutropenia
      patients. Multivariate analysis have demonstrated that IBM V20 and LSBM V15 were
      the independent factors affecting >= Grade 2 leukopenia. There is a correlation
      between low dose-volume parameters with acute bone marrow suppression. IBM V20,
      LSBM V15 and PBM V20 can be employed as the predictors of acute bone marrow
      suppression.

PMID- 29190964
TI  - Tumoral PD-L1 expression defines a subgroup of poor-prognosis vulvar carcinomas
      with non-viral etiology.
AB  - Vulvar cancer is rare but incidence rates are increasing due to an aging
      population and higher frequencies of young women being affected. In locally
      advanced, metastatic or recurrent disease prognosis is poor and new treatment
      modalities are needed. Immune checkpoint blockade of the PD-1/PD-L1 pathway is
      one of the most important advancements in cancer therapy in the last years. The
      clinical relevance of PD-L1 expression in vulvar cancer, however, has not been
      studied so far. We determined PD-L1 expression, numbers of CD3+ T cells, CD20+ B
      cells, CD68+ monocytes/macrophages, Foxp3+ regulatory T cells and CD163+ tumor
      associated macrophages by immunohistochemistry in 103 patients. Correlation
      analysis with clinicopathological parameters was undertaken; the cause-specific
      outcome was modeled with competing risk analysis; multivariate Cox regression was
      used to determine independent predictors of survival. Membranous PD-L1 was
      expressed in a minority of tumors, defined by HPV-negativity. Its presence
      geographically correlated with immunocyte-rich regions of cancer islets and was
      an independent prognostic factor for poor outcome. Our data support the notion
      that vulvar cancer is an immunomodulatory tumor that harnesses the PD-1/PD-L1
      pathway to induce tolerance. Accordingly, immunotherapeutic approaches might have
      the potential to improve outcome in patients with vulvar cancer and could
      complement conventional cancer treatment.

PMID- 29190966
TI  - MicroRNA-21 inhibits mitochondria-mediated apoptosis in keloid.
AB  - MicroRNA-21 acts as an oncogene by promoting cell proliferation and migration,
      whereas inhibiting apoptosis in majority of cancers. MicroRNA-21 is upregulated
      in human keloid fibroblasts. We hypothesized that microRNA-21 may contribute to
      pathogenesis of keloid fibroblasts. First, enhanced miR-21 but reduced
      mitochondrial-mediated apoptosis observed in keloid tissues indicated its
      importance in keloids development. Second, upregulation of microRNA-21 induced a
      decrease in the ratio of BAX to BCL-2 and suppressed mitochondrial fission in
      keloid fibroblasts. Third, by attenuating the decline in cellular mitochondrial
      membrane potential, overexpression of miR-21 suppressed cytochrome c release to
      the cytoplasm, followed by a decrease in the activity of intracellular caspase-9
      and caspase-3, suggesting that mitochondrial-mediated proapoptotic pathway was
      impaired. Simultaneously, intracellular reactive oxygen species were decreased,
      indicating microRNA-21 undermined oxidative stress. This phenotype was reversed
      by miR-21 inhibition. Therefore, our study demonstrates that inhibition of
      microRNA-21 induces mitochondrial-mediated apoptosis in keloid fibroblasts,
      proposing microRNA-21 as a potential therapeutic target in keloid fibroblasts.

PMID- 29190967
TI  - Differential prioritization of therapies to subtypes of triple negative breast
      cancer using a systems medicine method.
AB  - Triple negative breast cancer (TNBC) is a group of cancers whose heterogeneity
      and shortage of effective drug therapies has prompted efforts to divide these
      cancers into molecular subtypes. Our computational platform, entitled GenEx-TNBC,
      applies concepts in systems biology and polypharmacology to prioritize thousands
      of approved and experimental drugs for therapeutic potential against each
      molecular subtype of TNBC. Using patient-based and cell line-based gene
      expression data, we constructed networks to describe the biological perturbation
      associated with each TNBC subtype at multiple levels of biological action. These
      networks were analyzed for statistical coincidence with drug action networks
      stemming from known drug-protein targets, while accounting for the direction of
      disease modulation for coinciding entities. GenEx-TNBC successfully designated
      drugs, and drug classes, that were previously shown to be broadly effective or
      subtype-specific against TNBC, as well as novel agents. We further performed
      biological validation of the platform by testing the relative sensitivities of
      three cell lines, representing three distinct TNBC subtypes, to several small
      molecules according to the degree of predicted biological coincidence with each
      subtype. GenEx-TNBC is the first computational platform to associate drugs to
      diseases based on inverse relationships with multi-scale disease mechanisms
      mapped from global gene expression of a disease. This method may be useful for
      directing current efforts in preclinical drug development surrounding TNBC, and
      may offer insights into the targetable mechanisms of each TNBC subtype.

PMID- 29190968
TI  - Genetic variation at the microRNA binding site of CAV1 gene is associated with
      lung cancer susceptibility.
AB  - Single nucleotide polymorphism (SNP) may influence the genesis and development of
      cancer in a variety of ways depending on their location. Here we conducted a
      study in Chinese female non-smokers to investigate the relationship between
      rs1049337, rs926198 and the risk or survival of lung cancer. Further, we explored
      whether rs1049337 could alter the binding affinity between the mRNA of CAV1 and
      the corresponding microRNAs. Finally, we evaluated the relationship between
      expression level of CAV1 and prognosis of lung cancer. The results showed that
      the rs1049337-C allele and rs926198-C allele were the protective alleles of lung
      cancer risk. Haplotype analysis indicated that the C-C haplotype (constructed by
      rs1049337 and rs926198) was a protective haplotype for lung cancer risk. The
      result of luciferase reporter assay showed that rs1049337 can affect the binding
      affinity of CAV1 mRNA to the corresponding microRNAs both in A549 cell line and
      H1299 cell line. Compared with C allele, T allele had a relatively decreased
      luciferase activity. Compared with paired normal adjacent tissue or normal lung
      tissue, lung cancer tissue showed a relatively low level of CAV1. Refer to those
      patients at early stage of lung cancer, the expression level of CAV1 in patients
      at late stage of lung cancer was relatively low. In conclusion, the results
      indicated that rs1049337, it's a SNP located at 3'UTR region of CAV1 may affect
      lung cancer risk by altering the binding affinity between the mRNA of CAV1 and
      the corresponding microRNAs.

PMID- 29190969
TI  - Effect of oxytocin on the survival of random skin flaps.
AB  - Random flap transplantation is widely used to repair and rebuild skin soft
      tissue. However, such flaps exhibit poor survival. Plastic surgeons seek to
      improve flap survival. We explored whether oxytocin improved skin flap survival.
      Overlength random skin flaps (9 * 3 cm) were established on backs of 80 healthy
      male SD rats randomly divided into two groups. One group was injected daily with
      oxytocin (1 mg/kg; test group) and the other with normal saline (control group).
      On postoperative day 2, malondialdehyde (MDA) and superoxide dismutase (SOD)
      levels were measured. On postoperative day 7, the flap survival area was measured
      using transparent graph paper. Microvessel numbers were evaluated histologically
      by hematoxylin and eosin staining. VEGF expression was assessed
      immunohistochemically. Angiogenesis was evaluated via lead oxide-gelatin
      angiography and blood flow via laser Doppler flowmetry. In the test group
      compared with the control group, the flap survival rate and SOD activity were
      increased markedly, the MDA level was decreased, and according to hematoxylin and
      eosin staining, inflammation was significantly attenuated. In addition, the test
      group exhibited higher levels of VEGF and skin flap angiogenesis. Oxytocin
      improved flap survival rate by increasing microcirculation and angiogenesis and
      attenuating ischemia-reperfusion injury.

PMID- 29190970
TI  - Genome-wide identification of cancer/testis genes and their association with
      prognosis in a pan-cancer analysis.
AB  - Cancer/testis (CT) genes are excellent candidates for cancer immunotherapies
      because of their restrict expression in normal tissues and the capacity to elicit
      an immune response when expressed in tumor cells. In this study, we provide a
      genome-wide screen for CT genes with the identification of 745 putative CT genes.
      Comparison with a set of known CT genes shows that 201 new CT genes were
      identified. Integration of gene expression and clinical data led us to identify
      dozens of CT genes associated with either good or poor prognosis. For the CT
      genes related to good prognosis, we show that there is a direct relationship
      between CT gene expression and a signal for CD8+ cells infiltration for some
      tumor types, especially melanoma.

PMID- 29190971
TI  - Nomograms for predicting the overall and cancer-specific survival of patients
      with classical Hodgkin lymphoma: a SEER-based study.
AB  - The aim of this study was to establish nomograms, based on significant
      clinicopathologic parameters, for predicting the overall survival (OS) and the
      cancer-specific survival (CSS) of patients with classical Hodgkin lymphoma (CHL).
      The data of 43,330 CHL patients, diagnosed between 1983 and 2014, were
      obtainedfrom the database of the Surveillance, Epidemiology, and End Results
      (SEER) program. These patients were randomly divided into training (n = 30,339)
      and validation (n = 12,991) cohorts. The Kaplan-Meier method and Cox proportional
      hazards regression model were used to evaluate the prognostic effects of multiple
      clinicopathologic parameters on survival. Significant prognostic factors were
      combined to build nomograms. The predictive performance of nomograms was
      evaluated using the index of concordance (C-index) and calibration curves. In the
      training cohort, on univariate and multivariate analyses, age at diagnosis,
      gender, race, Ann Arbor stage, and histological type significantly correlated
      with the survival outcomes. These characteristics were used to establish
      nomograms. The nomograms showed good accuracy in predicting 1-, 5-, and 10-year
      OS and CSS, with a C-index of 0.794 (95% confidence interval [CI], 0.789-0.799)
      for OS and 0.760 (95% CI, 0.753-0.767) for CSS. In the validation cohort, the C
      index for nomogram-based predictions was 0.787 (95% CI, 0.779-0.795) for OS and
      0.769 (95% CI, 0.758-0.780) for CSS. All calibration curves revealed excellent
      consistency between predicted and actual survival. In summary, novel nomograms
      were established and validated to predict OS and CSS for patients with CHL. These
      new prognostic models could aid in improved prediction of survival outcomes
      leading to reasonable treatment recommendations.

PMID- 29190972
TI  - Development of estrogen receptor beta binding prediction model using large sets
      of chemicals.
AB  - We developed an ERbeta binding prediction model to facilitate identification of
      chemicals specifically bind ERbeta or ERalpha together with our previously
      developed ERalpha binding model. Decision Forest was used to train ERbeta binding
      prediction model based on a large set of compounds obtained from EADB. Model
      performance was estimated through 1000 iterations of 5-fold cross validations.
      Prediction confidence was analyzed using predictions from the cross validations.
      Informative chemical features for ERbeta binding were identified through analysis
      of the frequency data of chemical descriptors used in the models in the 5-fold
      cross validations. 1000 permutations were conducted to assess the chance
      correlation. The average accuracy of 5-fold cross validations was 93.14% with a
      standard deviation of 0.64%. Prediction confidence analysis indicated that the
      higher the prediction confidence the more accurate the predictions. Permutation
      testing results revealed that the prediction model is unlikely generated by
      chance. Eighteen informative descriptors were identified to be important to
      ERbeta binding prediction. Application of the prediction model to the data from
      ToxCast project yielded very high sensitivity of 90-92%. Our results demonstrated
      ERbeta binding of chemicals could be accurately predicted using the developed
      model. Coupling with our previously developed ERalpha prediction model, this
      model could be expected to facilitate drug development through identification of
      chemicals that specifically bind ERbeta or ERalpha.

PMID- 29190973
TI  - CLCA4 inhibits bladder cancer cell proliferation, migration, and invasion by
      suppressing the PI3K/AKT pathway.
AB  - Calcium activated chloride channel A4 (CLCA4), a tumor suppressor, was shown to
      contribute to the progression of several human cancers, while its role in bladder
      carcinoma remains unclear. In this study, we showed CLCA4 expression was down
      regulated in bladder carcinoma tissues and cells compared to adjacent non-tumor
      tissues and normal urothelial cells. Low CLCA4 expression was correlated with
      larger tumor size, advanced tumor stage, and poor prognosis in bladder carcinoma
      patients. Overexpression of CLCA4 profoundly attenuated the proliferation,
      growth, migratory and invasive capabilities of bladder cancer cells, whereas
      CLCA4 knockdown had the opposite effect. Mechanistically, CLCA4 is involved in
      PI3K/AKT signaling and its downstream molecules can promote bladder cancer cell
      proliferation. Additionally, CLCA4 could mediate the migration and invasion of
      bladder cancer cells by regulating epithelial-mesenchymal transition and PI3K/Akt
      activation. This study suggests that CLCA4 may represent a promising prognostic
      biomarker for bladder cancer and provides a possible mechanism for bladder cancer
      growth and invasion.

PMID- 29190974
TI  - MiR-3613-3p affects cell proliferation and cell cycle in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common types of malignant
      tumors with poor sensitivity to chemotherapy drugs and poor prognosis among
      patients. In the present study, we downloaded the original data from the Gene
      Expression Omnibus and compared gene expression profiles of liver cancer cells in
      patients with HCC with those of colon epithelial cells of healthy controls to
      identify differentially expressed genes (DEGs). After filtering target microRNAs
      (miRNA) from core DEGs, we cultured HepG2 cells in vitro, knocked down the miRNA
      and core mRNAs, and analyzed the effects. We found 228 differentially expressed
      genes between liver cancer tissue and healthy control tissue. We also integrated
      the protein-proteininteraction network and module analysis to screen 13 core
      genes, consisting of 12 up-regulated genes and 1 down-regulated gene. Five core
      genes were regulated hsa-miR-3613-3p, therefor we hypothesized that hsa-miR-3613
      3p was a critical miRNA. After the transfection procedure, we found that changes
      in hsa-miR-3613-3p were the most obvious. Therefore, we speculated that hsa-miR
      3613-3p was a main target miRNA. In addition, we transfected with si (BIRC5,
      CDK1, NUF2, ZWINT and SPC24), to target genes that can be targeted by miR-3613
      3p. Our data shows that BIRC5, NUF2, and SPC24 may be promising liver cancer
      biomarkers that may not only predict disease occurrence but also potential
      personalized treatment options.

PMID- 29190975
TI  - The association of plasma fibrinogen with clinicopathological features and
      prognosis in esophageal cancer patients.
AB  - Background: Numerous studies have shown that plasma fibrinogen was linked to
      esophageal cancer (EC) risk. However, the clinical significance of plasma
      fibrinogen in EC patients remain unclear and need to be further clarified.
      Results: A total of 2865 patients with EC from 11 published studies were included
      in this meta-analysis. The prognostic and clinical relevance of plasma fibrinogen
      were evaluated in EC patients. Statistical significance of the pooled hazard
      ratio (HR) was found for overall survival (OS), disease free survival (DFS) and
      recurrence-free survival (RFS) in EC. Subgroup analyses for OS were also
      performed to confirm the prognostic value of plasma fibrinogen. Additionally, the
      overall results indicated that elevated plasma fibrinogen was significantly
      associated with tumor invasion, lymph node metastasis (LNM) and clinical stage.
      Materials and Methods: A comprehensive literature retrieval was performed in
      PubMed, Embase, Cochrane database, Web of science and Chinese National Knowledge
      Infrastructure (CNKI) and Wanfang databases to identify relevant studies
      published prior to April 15, 2017. Conclusions: Elevated plasma fibrinogen could
      be served as a promising biomarker for predicting a poor prognosis and
      unfavorable clinicopathologic features for EC.

PMID- 29190976
TI  - Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER
      stress/UPR.
AB  - Hepatocellular carcinoma (HCC) is one of the most serious and deadly diseases
      worldwide with limited options for effective treatment. Biomarker-based active
      compound targeting therapy may shed some light on novel drugs for HCC. The
      endoplasmic reticulum (ER) stress and unfolded protein response (UPR) play
      important roles in the regulation of cell fate and have become novel signaling
      targets for the development of anticancer drugs. Celastrol, a triterpene from
      traditional Chinese medicine, has been reported to possess anti-tumor effects on
      various cancers. We, along with several other research groups, have recently
      reported that UPR was induced by celastrol in several different cancers,
      including hepatocellular carcinoma. However, UPR status in HCC still remains
      unclear. The role of ER stress and autophagy in response to celastrol also has
      yet to be elucidated. Our results demonstrated that celastrol could cause G2/M
      phase rest and inhibit proliferation in HepG2 and Bel7402. Exposure to celastrol
      resulted in the activation of the intrinsic apoptotic pathway, via ER stress and
      the UPR. In murine syngeneic model studies celastrol inhibited H22 tumor growth
      via the induction of ER stress and apoptosis. Our study suggests that celastrol
      is a potential drug for HCC therapy via targeting ER-stress/UPR.

PMID- 29190977
TI  - PPAR-alpha acutely inhibits functional activity of ASICs in rat dorsal root
      ganglion neurons.
AB  - Peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a lipid activated
      transcription factor of nuclear hormone receptor superfamily, can relieve pain
      through a rapid-response mechanism. However, little is known about the underlying
      mechanism. Herein, we report that PPAR-alpha activation acutely inhibits the
      functional activity of acid-sensing ion channels (ASICs), key sensors for
      extracellular protons, in rat dorsal root ganglion (DRG) neurons. Pre-application
      of PPAR-alpha agonist GW7647 for 2 min decreased the amplitude of proton-gated
      currents mediated by ASICs in a concentration-dependent manner. GW7647 shifted
      the concentration-response curve for proton downwards, with a decrease of 36.9 +/
      2.3% in the maximal current response to proton. GW7647 inhibition of proton
      gated currents can be blocked by GW6471, a selective PPAR-alpha antagonist.
      Moreover, PPAR-alpha activation decreased the number of acidosis-evoked action
      potentials in rat DRG neurons. Finally, peripheral administration of GW7647 dose
      dependently relieved nociceptive responses to injection of acetic acid in rats.
      These results indicated that activation of peripheral PPAR-alpha acutely
      inhibited functional activity of ASICs in a non-genomic manner, which revealed a
      novel mechanism underlying rapid analgesia through peripheral PPAR-alpha.

PMID- 29190978
TI  - Pooling-analysis on hMLH1 polymorphisms and cancer risk: evidence based on 31,484
      cancer cases and 45,494 cancer-free controls.
AB  - To elucidate the veritable relationship between three hMLH1 polymorphisms
      (rs1800734, rs1799977, rs63750447) and cancer risk, we performed this meta
      analysis based on overall published data up to May 2017, from PubMed, Web of
      knowledge, VIP, WanFang and CNKI database, and the references of the original
      studies or review articles. 57 publications including 31,484 cancer cases and
      45,494 cancer-free controls were obtained. The quality assessment of six articles
      obtained a summarized score less than 6 in terms of the Newcastle-Ottawa Scale
      (NOS). All statistical analyses were calculated with the software STATA (Version
      14.0; Stata Corp, College Station, TX). We found all the three polymorphisms can
      enhance overall cancer risk, especially in Asians, under different genetic
      comparisons. In the subgroup analysis by cancer type, we found a moderate
      association between rs1800734 and the risk of gastric cancer (allele model: OR =
      1.14, P = 0.017; homozygote model: OR = 1.33, P = 0.019; dominant model: OR =
      1.27, P = 0.024) and lung cancer in recessive model (OR = 1.27, P = 0.024). The G
      allele of rs1799977 polymorphism was proved to connect with susceptibility of
      colorectal cancer (allele model: OR = 1.21, P = 0.023; dominate model: OR = 1.32,
      P <0.0001) and prostate cancer (dominate model: OR = 1.36, P <0.0001). Rs63750447
      showed an increased risk of colorectal cancer, endometrial cancer and gastric
      cancer under all genetic models. These findings provide evidence that hMLH1
      polymorphisms may associate with cancer risk, especially in Asians.

PMID- 29190979
TI  - Resting-state functional connectivity of the dorsal frontal cortex predicts
      subcortical vascular cognition impairment.
AB  - Functional magnetic resonance imaging (fMRI) studies have revealed group
      differences in the frontal area between the subcortical vascular cognition
      impairment (SVCI) patients and the controls. However, most of the existing
      research focused on average differences between the two groups, and therefore had
      limited clinical applicability. The aim of our study was to investigate whether
      inter-regions functional connectivity of the dorsal frontal cortex (DFC) can be
      used to discriminate the SVCI from the controls at the level of the individual.
      Thirty-two SVCI patients and 32 demographically similar healthy individuals
      underwent resting-state functional magnetic resonance imaging. The DFC, derived
      from a prior atlas, was divided into 10 clusters. Features based on DFC were
      obtained through functional connectivity analysis between pairs of DFC. A
      nonlinear kernel support vector machine was used for classification and validated
      using 8-fold cross validation. An excellent classification accuracy was obtained
      from both the left and the right DFC functional connectivity (accuracy=75.07%,
      sensitivity=81.57% and specificity=61.71%; accuracy=45.38%, sensitivity=60.74%
      and specificity=39.48%; P<0.001). These findings shed further light on the
      pathogenesis of SVCI and showed promising classification performance using
      machine learning analysis based on DFC fMRI data, which may be useful for the
      differentiation of SVCI.

PMID- 29190980
TI  - Transplanted olfactory ensheathing cells restore retinal function in a rat model
      of light-induced retinal damage by inhibiting oxidative stress.
AB  - There is still not an effective treatment for continuous retinal light exposure
      and subsequent photoreceptor degeneration. Olfactory ensheathing cell (OEC)
      transplantation has been shown to be neuroprotective in spinal cord, and optic
      nerve injury and retinitis pigmentosa. However, whether OECs protect rat
      photoreceptors against light-induced damage and how this may work is unclear.
      Thus, to elucidate this mechanism, purified rat OECs were grafted into the
      subretinal space of a Long-Evans rat model with light-induced photoreceptor
      damage. Light exposure decreased a- and b- wave amplitudes and outer nuclear
      layer (ONL) thickness, whereas the ONL of rats exposed to light for 24 h after
      having received OEC transplants in their subretinal space was thicker than the
      PBS control and untreated groups. A- and b- wave amplitudes from
      electroretinogram of OEC-transplanted rats were maintained until 8 weeks post OEC
      transplantation. Also, transplanted OECs inhibited formation of reactive oxygen
      species in retinas exposed to light. In vitro experiments showed that OECs had
      more total antioxidant capacity in a co-cultured 661W photoreceptor cell line,
      and cells were protected from damage induced by hydrogen-peroxide. Thus,
      transplanted OECs preserved retinal structure and function in a rat model of
      light-induced degeneration by suppressing retinal oxidative stress reactions.

PMID- 29190981
TI  - A20 enhances the radiosensitivity of hepatocellular carcinoma cells to 60Co-gamma
      ionizing radiation.
AB  - The radioresistance of hepatocellular carcinoma (HCC) cells is a critical
      obstacle for effectively applying radiotherapy (RT) in HCC treatment. NF-kappaB,
      an important transcription factor, can influence critical cell fate decisions by
      promoting cell survival or anti-apoptosis in response to cell-stress, e.g.
      chemotherapies or ionizing radiation (IR). A20, also named as tumor necrosis
      factor alpha induced protein 3 (TNFAIP3), is a dominant negative regulator of NF
      kappaB pathway and its functions in HCC are largely unknown. The present work
      aimed to reveal the role of A20 plays in affecting the radiosensitivity of HCC
      cells. Higher expression of A20 was detected in hepatic non-tumor cell line or
      clinical specimens compared with HCC cell lines or clinical specimens. A20
      decreased the expression of proteins mediating cellular stress/injury response or
      epithelial-mesenchymal transition (EMT) process. Overexpression of A20 via
      adenovirus enhanced the effect of 60Co-gamma ionizing radiation (IR) on HCC
      cells' injury, e.g. G2/M arrest or DNA double strands break (DSB). Moreover, A20
      also enhanced the in vitro or in vivo survival inhibiting of HCC cells induced by
      IR. These results reveal the roles of A20 in HCC radiosensitization and
      overexpression of A20 would be a novel strategy for HCC radiotherapy.

PMID- 29190984
TI  - Prognostic value of smoking status in non-small-cell lung cancer patients treated
      with immune checkpoint inhibitors: a meta-analysis.
AB  - Immune checkpoint inhibitors (ICIs) have emerged as a new treatment option for
      patients with advanced non-small-cell lung cancer (NSCLC). Some studies with ICIs
      in NSCLC suggested that smoking history was associated with improved survival
      outcomes. We conducted this meta-analysis to investigate if survival benefits of
      ICIs in patients with advanced NSCLC are different according to smoking status.
      Electronic databases were searched for eligible studies. We included randomized
      controlled trials with the data of survival outcomes and extracted progression
      free survival (PFS) or overall survival (OS) stratified by smoking status. From 6
      studies, 2,389 ever-smokers and 413 never-smokers were included in the meta
      analysis. In first-line treatment setting, ICIs tended to improve PFS in patients
      with smoking history (HR = 0.85 [95% CI, 0.71-1.10], P = 0.07). For never-smokers
      with advanced NSCLC, chemotherapy, not ICIs, was significantly associated with
      improvement of PFS (HR = 2.30 [95% CI, 1.23-4.28], P = 0.009). In more than
      second-line setting, ICIs significantly prolonged OS over that with chemotherapy
      in ever-smokers (HR = 0.70 [95% CI, 0.63-0.79], P < 0.00001). For never-smokers
      with NSCLC, however, ICIs failed to significantly improve OS (HR = 0.79 [95% CI,
      0.59-1.06], P = 0.12). In conclusion, this meta-analysis indicates that ICIs can
      prolong survival over that with chemotherapy in ever-smokers with advanced NSCLC.
      However, ICIs failed to improve survival in never-smokers. These results suggest
      that smoking status may be a predictive marker for survival benefits to ICIs.

PMID- 29190983
TI  - Ginkgetin induces autophagic cell death through p62/SQSTM1-mediated autolysosome
      formation and redox setting in non-small cell lung cancer.
AB  - Promoting cell death by autophagy could be a novel treatment for cancer. The
      major player in autophagy, p62, serves as a good therapeutic target. Ginkgetin, a
      biflavonoid from Ginkgo biloba leaves, exhibited promising anticancer activity in
      non-small cell lung cancer cell lines, with an IC50 lower than that of cisplatin.
      This anticancer effect of ginkgetin was illustrated in a xenograft nude mouse
      model. Ginkgetin induced autophagic cell death in A549 cells, and this effect was
      markedly reversed by chemical and genetic approaches. Ginkgetin showed potential
      binding affinity to p62. Upregulation of p62 through chemical and genetic means
      decreased cell death, lysosome acidification, and autophagosome formation, which
      consequently disrupted autolysosome formation. In addition, the decreased
      autophagy induced by p62 overexpression increased Nrf2/ARE activity and the
      oxygen consumption rate and decreased on formation of reactive oxygen species.
      These phenomena were exhibited in a reciprocal manner when p62 was knocked down.
      Thus, p62 may be a potential target in ginkgetin-induced autophagic cell death,
      and ginkgetin could be developed as a novel anticancer drug.

PMID- 29190982
TI  - Diagnostic performance enhancement of pancreatic cancer using proteomic
      multimarker panel.
AB  - Due to its high mortality rate and asymptomatic nature, early detection rates of
      pancreatic ductal adenocarcinoma (PDAC) remain poor. We measured 1000 biomarker
      candidates in 134 clinical plasma samples by multiple reaction monitoring-mass
      spectrometry (MRM-MS). Differentially abundant proteins were assembled into a
      multimarker panel from a training set (n=684) and validated in independent set
      (n=318) from five centers. The level of panel proteins was also confirmed by
      immunoassays. The panel including leucine-rich alpha-2 glycoprotein (LRG1),
      transthyretin (TTR), and CA19-9 had a sensitivity of 82.5% and a specificity of
      92.1%. The triple-marker panel exceeded the diagnostic performance of CA19-9 by
      more than 10% (AUCCA19-9 = 0.826, AUCpanel= 0.931, P < 0.01) in all PDAC samples
      and by more than 30% (AUCCA19-9 = 0.520, AUCpanel = 0.830, P < 0.001) in patients
      with normal range of CA19-9 (<37U/mL). Further, it differentiated PDAC from
      benign pancreatic disease (AUCCA19-9 = 0.812, AUCpanel = 0.892, P < 0.01) and
      other cancers (AUCCA19-9 = 0.796, AUCpanel = 0.899, P < 0.001). Overall, the
      multimarker panel that we have developed and validated in large-scale samples by
      MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.

PMID- 29190985
TI  - Prognostic value of B7-H3 expression in patients with solid tumors: a meta
      analysis.
AB  - Increasing evidence suggests B7-H3 is aberrantly expressed in various cancers,
      though its prognostic significance in solid tumors remains controversial. We
      therefore performed a meta-analysis to clarify the prognostic value of B7-H3
      expression in human solid tumors. The PubMed and Embase databases were searched,
      and 28 studies involving 4623 patients were ultimately included in the analysis.
      Hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized as effect
      estimates to evaluate the association between B7-H3 expression and overall
      survival (OS), progression-free survival (PFS) and recurrence-free survival
      (RFS). The pooled results showed B7-H3 was associated with poor OS (HR = 1.58;
      95% CI: 1.32-1.90; P < 0.00001) and PFS (HR = 1.67; 95% CI: 1.05-2.65; P =
      0.031), but not RFS (HR = 1.17; 95% CI: 0.89-1.53; P = 0.267). These results
      suggest B7-H3 is a negative predictor of OS and PFS in patients with solid
      tumors. B7-H3 may thus be a useful prognostic biomarker and therapeutic target
      for human solid tumors. However, further studies will be needed to more precisely
      determine the prognostic value of B7 H3 expression.

PMID- 29190986
TI  - The relationship between obstructive sleep apnea and obesity hypoventilation
      syndrome: a systematic review and meta-analysis.
AB  - Obstructive Sleep Apnea and Obesity Hypoventilation Syndrome are two similar
      diseases. Obstructive Sleep Apnea has been receiving more and more attention
      while the diagnostic rate of Obesity Hypoventilation Syndrome is not high. Few
      studies directly evaluated the relationship between them. We systematically
      analyzed the relevance of the two diseases. MEDLINE(r), EMBASE(r) and the
      Cochrane Library were carried out to find studies until May 2017. Pooled mean
      difference and 95% confidence interval were calculated to evaluate the value of
      clinical and physiologic variables in the prediction of Obesity Hypoventilation
      Syndrome. 9 Studies (n = 2085) fulfilled the predefined selection criteria.
      Totally 575 patients (28%) with Obesity Hypoventilation Syndrome were diagnosed
      from 2085 Obstructive Sleep Apnea patients. Among clearly diagnosed Obstructive
      Sleep Apnea patients, higher Body Mass Index levels(mean difference:4.72 kg/m2;
      95% confidence interval: 4.26 to 5.17; p < 0.00001), higher Apnea-Hypopnea Index
      (mean difference: 8.36; 95% confidence interval: -3.88 to -2.84; p < 0.00001),
      greater neck circumference (mean difference:1.01; 95% confidence interval: 0.10
      to 1.92; p = 0.03) and lower percent predicted FEV1 (mean difference:-10.28; 95%
      confidence interval:-11.33 to -9.22; p < 0.00001)were associated with the
      occurrence with obesity hypoventilation syndrome. We should be highly skeptical
      of obesity hypoventilation syndrome in Obstructive Sleep Apnea patients with
      these factors as early identification and appropriate treatment can improve
      prognosis.

PMID- 29190987
TI  - Efficacy of anti-VEGF agents in the treatment of elderly hepatocellular
      carcinoma: a systematic review.
AB  - Purpose: We aimed to investigate the role of anti-vascular endothelial growth
      factor (VEGF) agents, including tyrosine-kinase inhibitors or monoclonal anti
      bodies, in the treatment of elderly hepatocellular carcinoma (HCC) patients.
      Materials and Methods: Databases from PubMed, Web of Science and abstracts
      presented at ASCO meeting up to March 31, 2017 were searched to identify relevant
      studies. The endpoints were overall survival (OS) and progression-free survival
      (PFS). Data were examined using age cutoffs of 65 years. Results: A total of
      1,309 elderly (aged >= 65 years) HCC patients from seven trials were included for
      analysis. Our results demonstrated that the use of anti-VEGF agents MTAs in
      patients aged >= 65 years significantly improved PFS (HR 0.65, 95% CI: 0.55-0.76,
      p < 0.001) but not for OS (HR 0.87, 95% CI: 0.73-1.05, p = 0.15). Sub-group
      analysis according to treatment line showed that the use of anti-VEGF agents as
      second-line treatment significantly improved PFS (HR 0.55, 95% CI: 0.45-0.67, p <
      0.001) and marginally improved OS (HR 0.83, 95% CI: 0.68-1.01, p = 0.061).
      Additionally, no survival benefits were observed in elderly HCC received first
      line anti-VEGF treatments in terms of PFS (HR 0.87, 95% CI: 0.67-1.13, p = 0.29)
      and OS (HR 1.19, 95% CI: 0.74-1.36, p = 0.47). No publication bias was detected
      by Begg's and Egger's tests for OS. Conclusions: The findings of this study show
      that elderly HCC patients who relapsed after a first-line sorafenib treatment
      obtains a survival benefits from anti-VEGF agents rechallenge. Further studies
      are recommended to search for predictors of good responders in these patients
      received anti-VEGF agents.

PMID- 29190988
TI  - Association of Ezrin expression with the progression and prognosis of
      gastrointestinal cancer: a meta-analysis.
AB  - Background: Ezrin, a cytoskeletal protein, is involved in cell adhesion. Several
      studies have been performed to explore the association between Ezrin and
      gastrointestinal cancers, but the results are inconclusive. This meta-analysis
      aims to assess the prognostic value of Ezrin. Materials and Methods/Findings:
      PubMed and EMBASE were searched. Pooled hazard ratio (HR), odds ratio (OR) and
      95% confidence intervals (CI) were utilized to evaluate the association between
      Ezrin expression and various clinical parameters. 2701 patients from 19 studies
      were included in the meta-analysis. For gastric cancer, Ezrin expression was
      associated with tumor grade (OR 2.32, 95% CI 1.53-3.52), TNM stage (OR 4.69, 95%
      CI 1.38-15.89), lymph node involvement (OR 3.96, 95% CI 1.47-10.70) and overall
      survival (HR 1.88, 95% CI 1.33-2.66). In colorectal cancer, Ezrin expression was
      associated with tumor grade (OR 3.94, 95% CI 2.10-3.78), TNM stage (OR 5.66, 95%
      CI 1.41-22.67), lymph node metastasis (OR 9.52, 95% CI 3.93-23.02), distant
      metastasis (OR 3.06, 95% CI 1.77-5.31), disease free survival (HR 2.48, 95% CI
      1.44-4.28). For esophageal cancer, Ezrin expression was associated with lymph
      node metastasis (OR 2.07, 95% CI 1.00-4.28) and overall survival (HR 1.49, 95% CI
      1.17-1.89). Conclusions: Ezrin expression is significantly associated with tumor
      grade, TNM stage, and lymph node metastasis in gastric and colorectal cancers.
      For gastric cancers, Ezrin is useful in predicting distant metastasis. Survival
      data showed that high Ezrin expression is associated with poor prognosis in
      gastric, colorectal and esophageal cancers. Our findings suggest that Ezrin might
      be a potential biomarker in several gastrointestinal cancers.

PMID- 29190989
TI  - Aberrant pattern of regional cerebral blood flow in Alzheimer's disease: a voxel
      wise meta-analysis of arterial spin labeling MR imaging studies.
AB  - Many studies have applied arterial spin labeling (ASL) to characterize cerebral
      perfusion patterns of Alzheimer's disease (AD). However, findings across studies
      are not conclusive. A quantitatively voxel-wise meta-analysis to pool the resting
      state ASL studies that measure regional cerebral blood flow (rCBF) alterations in
      AD was conducted to identify the most consistent and replicable perfusion pattern
      using seed-based d mapping. The meta-analysis, including 17 ASL studies
      encompassing 327 AD patients and 357 healthy controls, demonstrated that
      decreased rCBF in AD patients relative to healthy controls were consistently
      identified in the bilateral posterior cingulate cortices (PCC)/precuneus,
      bilateral inferior parietal lobules (IPLs), and left dorsolateral prefrontal
      cortex. The meta-regression analysis showed that more severe cognitive impairment
      in the AD samples correlated with greater decreases of rCBF in the bilateral PCC
      and left IPL. This study characterizes an aberrant ASL-rCBF perfusion pattern of
      AD involving the posterior default mode network and executive network, which are
      implicated in its pathophysiology and hold promise for developing imaging
      biomarkers.

PMID- 29190990
TI  - Smoking and the risk of diabetic nephropathy in patients with type 1 and type 2
      diabetes: a meta-analysis of observational studies.
AB  - Background: Conflicting evidence exists for observational studies on whether
      tobacco smoking is a risk factor for diabetic nephropathy (DN) in patients with
      type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In this meta-analysis, we
      aimed to assess the effects of tobacco smoking on the development of DN.
      Materials and Methods: We searched MEDLINE and EMBASE databases from their
      inception to March 31st, 2017 for cross-sectional, case-control, and prospective
      cohort studies. We screened reference lists of retrieved articles. Summary
      relative risks (SRRs) and 95% confidence intervals (CIs) were calculated using a
      random-effects model. Results: A total of nineteen observational studies (1 case
      control, 8 cross-sectional and 10 prospective cohort studies) were identified,
      involving more than 78,000 participants and a total of 17,832 DN cases. Compared
      with never-smokers, there was an augmented SRR (95% CI) of DN in ever-smokers in
      patients with T1DM (1.31 [1.06-1.62]; P = 0.006) and T2DM (1.44 [1.24-1.67]; P <
      0.001), respectively. In patients with T1DM, the SRR (95% CI) was 1.25 (0.86
      1.83) for microalbuminuria only, 1.27 (1.10-1.48) for macroalbuminuria only, and
      1.06 (0.97-1.15) for end-stage renal disease (ESRD). In patients with T2DM, the
      SRR (95% CI) associated with ever smoking was 1.46 (0.94-2.26) for
      microalbuminuria only, 1.72 (1.04-2.84) for macroalbuminuria only, and 1.10 (0.36
      3.33) for ESRD. Conclusions: Our meta-analysis suggests evidence for cigarette
      smoking as an independent risk factor for the development of DN in patients with
      both T1DM and T2DM.

PMID- 29190991
TI  - Association of HLA-DRB1 polymorphism with Alzheimer's disease: a replication and
      meta-analysis.
AB  - Genome-wide association studies (GWAS) have identified one single-nucleotide
      polymorphism (SNP) rs9271192 within HLA-DRB1 as a risk factor for Alzheimer's
      disease (AD) in Caucasians. The effect of rs9271192 on AD needed to be verified
      in other ethnic cohorts. In order to evaluate the association between HLA-DRB1
      rs9271192 polymorphism and late-onset AD (LOAD) in the Northern Han Chinese
      population, we recruited 982 LOAD patients and 1344 sex- and age-matched healthy
      controls. The results showed that HLA-DRB1 rs9271192 was associated with LOAD
      (genotype P = 0.015, allele P = 0.04). The results of logistic regression
      revealed the C allele homozygosity strongly increased the risk of LOAD under a
      recessive model in the total sample (P = 0.004, OR =2.069, 95% CI = 1.262-3.434).
      When these data were stratified by apolipoprotein E (APOE) epsilon4 status, the
      observed association was confined to APOE epsilon4 non-carriers (additive model:
      P=0.048, OR =1.191, 95% CI =1.001-1.417; recessive model: P < 0.001, OR = 2.601,
      95% CI =1.519-4.566). Furthermore, meta-analysis after sensitive analysis
      confirmed that rs9271192 within HLA-DRB1 increased the risk of LOAD (OR = 1.12,
      95% CI = 1.08-1.15). To summarize, the C allele in HLA-DRB1 rs9271192 may be an
      independent risk factor for LOAD.

PMID- 29190992
TI  - Prognostic role of long non-coding RNA LINC00152 in Chinese cancer patients: a
      meta-analysis.
AB  - The role of long intergenic non-coding RNA 152 (LINC00152) in predicting the
      prognosis of cancer has been investigated but results remain inconclusive and
      inconsistent. A meta-analysis was performed to explore the effect of LINC00152 on
      cancer prognosis. PubMed and ScienceDirect were searched for suitable studies and
      the results of 10 studies with a total of 775 patients were pooled. Pooled hazard
      ratios (HRs) and odds ratios (ORs) were calculated to assess the prognostic value
      of LINC00152. The results revealed that tumour patients with high LINC00152
      expression were more likely to have lymph node metastasis (OR = 2.94, 95% CI 1.97
      4.40, P < 0.001) and unfavourable tumour-node-metastasis stage (grade III/IV vs.
      I/II: OR = 3.07, 95% CI 1.69-5.59, P < 0.001). In addition, high LINC00152
      expression levels were significantly associated with poor overall survival
      (pooled HR = 1.99, 95% CI 1.54-2.56, P < 0.001). The results suggest that high
      LINC00152 expression may serve as a predictive biomarker for the poor prognosis
      of various cancers in the Chinese population.

PMID- 29190993
TI  - Whether partial colectomy is oncologically safe for patients with transverse
      colon cancer: a large population-based study.
AB  - Due to special tumor location and technical difficulty of transverse colon cancer
      (TCC), partial colectomy (PC) is being widely applied in selected TCC patients,
      instead of extended hemicolectomy (HC). However, the oncological safety of this
      less aggressive surgical approach is not well studied. Here, we identified 10344
      TCC patients from Surveillance, Epidemiology, and End-Results (SEER) database.
      The surgical treatment for those patients included PC and HC. Firstly, we
      compared lymph nodes evaluations between patients treated with HC and PC,
      including median number of nodes, the rate of nodes >= 12 and the rate of node
      positivity. Then, 5-year cancer specific survival (CSS) was obtained. Kaplan
      Meier methods and Cox regression models were performed to assess the correlations
      between prognostic factors and long-term survival. Despite of less node examined
      by PC, the rate of node positivity was equal between PC and HC, suggesting node
      retrieval under PC was adequate to tumor stage. In addition, the 5-year CSS for
      patients who underwent PC were 67.5%, which was similar to patients who received
      HC (66.5%). The result after propensity score matching also confirmed the
      equivalent survival outcome between HC and PC. However, subgroup analyses showed
      that patients with tumor size >= 5 cm could not obtain survival benefit from PC.
      Furthermore, surgical approach was not considered as independent prognostic
      factor for TCC patients. Therefore, although PC is a less aggressive surgical
      approach, it should be a safe and feasible option for selected TCC patients.

PMID- 29190994
TI  - Hemorrhage of brain metastasis is a poor prognostic factor in hepatocellular
      carcinoma patients.
AB  - It is unclear whether hemorrhage of brain metastasis is a poor prognostic factor
      in patients with hepatocellular carcinoma. We conducted a retrospective cohort
      study to compare overall survival between hemorrhage and no-hemorrhage groups of
      hepatocellular carcinoma patients with brain metastasis. Hepatocellular carcinoma
      patients with brain metastasis treated between June 2000 and June 2016 at the
      Cancer Hospital of Guangxi Medical University were retrospectively reviewed.
      Clinical characteristics and overall survival were compared between patients with
      (n = 11) and without (n = 25) hemorrhage of brain metastasis. Univariate and
      multivariate survival analyses showed hemorrhage to be a poor prognostic factor
      (hazard ratio = 5.812, 95% confidence interval: 1.399-24.142, p = 0.015).
      Patients with hemorrhage had a shorter median survival than those without
      hemorrhage (4 weeks vs 8 weeks, p = 0.001). These results suggest hemorrhage of
      brain metastasis is a poor prognostic factor in patients with hepatocellular
      carcinoma patients.

PMID- 29190995
TI  - Predictors of hypertension urgency in primary aldosteronism patients during the
      first 24 hours after surgery.
AB  - Study about blood pressure variation in the first 24 hours post-operation is
      limited in patients with adrenal aldosterone-producing adenoma. We aim to
      evaluate the potential predictors for postoperative hypertension urgency during
      the first 24 hours after laparoscopic adrenalectomy in patients with aldosterone
      producing adenoma. Clinical data of 177 patients with aldosterone-producing
      adenoma were retrospectively collected from January 2009 to December 2015 and the
      potential factors that may influence postoperative blood pressure during the
      first 24 hours after surgery were analyzed. The factors included gender, age,
      body mass index, preoperative maximum systolic blood pressure, number of
      antihypertensive medicines, preoperative spironolactone treatment, duration of
      hypertension, surgical method and approach, adenoma diameter, preoperative
      proteinuria, estimated glomerular filtration rate, serum potassium and serum
      aldosterone. Univariate and multivariate regression analyses were used to
      evaluate the relationship between the above variables and postoperative
      hypertension urgency. We found that the proportion of patients with a higher
      systolic blood pressure >= 160 mmHg and >= 180 mmHg were significantly increased
      post-operation (both p < 0.001). In multivariate analysis, the maximum systolic
      blood pressure was an independent predictor of postoperative hypertension
      urgency, and the cut-off point was 157 mmHg with the sensitivity of 66% and
      specificity of 82%. Multivariable analysis also showed that preoperative maximum
      systolic blood pressure and number of antihypertensive medicines were independent
      risk factors for higher postoperative systolic blood pressure. This study was
      derived from a high volume adrenal tumor center, and these data may provide a
      potential tool to guide preoperative counseling.

PMID- 29190996
TI  - Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus
      in the Asia-Pacific region beyond the Barcelona Clinic Liver Cancer treatment
      algorithms: a review and update.
AB  - Portal vein tumor thrombus (PVTT) usually worsens prognosis of hepatocellular
      carcinoma (HCC), as characterized by aggressive disease progression, impaired
      liver function and tolerance to treatment. Conventionally, the European
      Association for the Study of the Liver (EASL) and the American Association for
      the Study of Liver Diseases (AASLD) accepted the Barcelona Clinical Liver Cancer
      (BCLC) treatment algorithms, identifying PVTT as an absolute contra-indication of
      surgical resection for HCC. HCC-PVTT patients are offered sorafenib as the
      standard treatment. Evidently, SHARP and Asia-Pacific trials demonstrated that
      sorafenib only improves overall survival by approximately 3 months in patients
      with advanced HCC. Besides, BCLC treatment algorithm does not provide different
      therapeutic recommendations for different degree of PVTT, and only supports
      single treatment option for each stage of HCC rather than a combination of
      comprehensive treatments, which limited individual and best care for every HCC
      PVTT patients. In the past few years, many surgeons do not restrict surgical
      resection to HCC with PVTT. There have been new reports demonstrated that
      surgical treatment is feasible for selected HCC-PVTT patients with resectable
      tumor and moderate liver function to prolong survival period and elevate life
      quality as long as PVTT limited to the first-order branch, whereas non-surgical
      treatments fail to provide comparable therapeutic effects. At present, guidelines
      on HCC management from mainland China, Japan, and Hong Kong have been updated and
      a consensus of Asia-Pacific experts has established that portal venous invasion
      is not an absolute contradiction of surgical resection for HCC. This review
      summarized the emerging data on surgical resection for HCC-PVTT patients beyond
      the BCLC treatment algorithms and discussed recent therapeutic conceptualchanges
      in the Asia-Pacific region.

PMID- 29190998
TI  - Radiological and nuclear medicine imaging of sarcoidosis.
AB  - Sarcoidosis is a multisystem chronic inflammatory disease of unknown etiology
      characterized by widespread growth of non-caseating granulomas. The diagnosis of
      sarcoidosis is based on clinical and imaging presentation, histologic
      confirmation and the absence of alternative diseases. Radiology and Nuclear
      Medicine play an essential role in the diagnostic work-up of patients with
      sarcoidosis to assess disease extent and activity. In addition, imaging
      modalities have shown their potential in managing these patients in terms of
      treatment response and prognostic assessment. Sarcoidosis has a predilection for
      chest involvement, showing typical and atypical manifestations in the lungs,
      airways and hilar/mediastinal lymph nodes. Chest radiography (X-ray) still plays
      an important role in suggesting diagnosis for cases with typical presentation of
      sarcoidosis, while computed tomography (CT) has higher accuracy in detecting
      early stage disease and in narrowing differential diagnosis, particularly in
      atypical manifestations. For extrathoracic involvement, both CT and MR (magnetic
      resonance) have comparable performance even though MR is the modality of choice
      for assessing neurosarcoidosis and cardiac sarcoidosis. In the last decades
      positron emission tomography/CT (PET/CT) has demonstrated an increasing and
      relevant value in assessing disease extent and activity, treatment planning and
      therapy response, with a crucial role in the management of cardiac sarcoidosis.
      In this article, an overview of the possible imaging manifestations of thoracic
      and extrathoracic sarcoidosis and current concepts on staging, response
      assessment and prognosis is provided. Finally, the potential applications of non
      FDG radiotracers is briefly discussed.

PMID- 29190999
TI  - Animal models for the study of inflammatory bowel diseases: a meta-analysis on
      modalities for imaging inflammatory lesions.
AB  - Inflammatory bowel diseases are lifelong disorders affecting the gastrointestinal
      tract characterized by intermittent disease flares and periods of remission with
      a progressive and destructive nature. Unfortunately, the exact etiology is still
      not completely known, therefore a causal therapy to cure the disease is not yet
      available. Current treatment options mainly encompass the use of non-specific
      anti-inflammatory agents and immunosuppressive drugs that cause significant side
      effects that often have a negative impact on patients' quality of life. As the
      majority of patients need a long-term follow-up it would be ideal to rely on a
      non-invasive technique with good compliance. Currently, the gold standard
      diagnostic tools for managing IBD are represented by invasive procedures such as
      colonoscopy and histopathology. Nevertheless, recent advances in imaging
      technology continue to improve the ability of imaging techniques to non
      invasively monitor disease activity and treatment response in preclinical models
      of IBD. Novel and emerging imaging techniques not only allow direct visualization
      of intestinal inflammation, but also enable molecular imaging and targeting of
      specific alterations of the inflamed murine mucosa. Furthermore, molecular
      imaging advances allow us to increase our knowledge on the critical biological
      pathways involved in disease progression by characterizing in vivo processes at a
      cellular and molecular level and enabling significant improvements in the
      understanding of the etiology of IBD. This review presents a critical and updated
      overview on the imaging advances in animal models of IBD. Our aim is to highlight
      the potential beneficial impact and the range of applications that imaging
      techniques could offer for the improvement of the clinical monitoring and
      management of IBD patients: diagnosis, staging, determination of therapeutic
      targets, monitoring therapy and evaluation of the prognosis, personalized
      therapeutic approaches.

PMID- 29191000
TI  - In-vivo imaging of tumor-infiltrating immune cells: implications for cancer
      immunotherapy.
AB  - Dynamic interactions between tumor cells and immune cells promote the initiation,
      progression, metastasis and therapy-resistance of cancer. With respect to
      immunotherapy, immune cell populations such as cytotoxic CD8+ T-cells, CD56+ NK
      cells and myeloid phagocytic cells play decisive roles. From an imaging
      perspective, the immune system displays unique challenges, which have
      implications for the design and performance of studies. The immune system
      comprises highly mobile cells that undergo distinct phases of development and
      activation. These cells circulate through several compartments during their
      active life span and accumulate in rather limited numbers in cancer lesion, where
      their effector phenotype further diversifies. Given these features, accurate
      evaluation of the tumor microenvironment and its cellular components during anti
      cancer immunotherapy is challenging. In-vivo imaging currently offers
      quantitative and sensitive modalities that exploit long-lived tracers to
      interrogate, e.g. distinct immune cell populations, metabolic phenotypes,
      specific targets relevant for therapy or critical for their effector function.
      This review provides a comprehensive overview of current status for in-vivo
      imaging tumor-infiltrating immune cell populations, focusing on lymphocytes, NK
      cells and myeloid phagocytic cells, with emphasis on clinical translation.

PMID- 29190997
TI  - Inflammatory microenvironment in the initiation and progression of bladder
      cancer.
AB  - Accumulating evidence suggests the idea that chronic inflammation may play a
      critical role in various malignancies including bladder cancer and long-term
      treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is significantly
      effective in reducing certain cancer incidence and mortality. However, the
      molecular mechanisms leading to malignant transformation and the progression of
      bladder cancer in a chronically inflammatory environment remain largely unknown.
      In this review, we will describe the role of inflammation in the formation and
      development of bladder cancer and summarize the possible molecular mechanisms by
      which chronic inflammation regulates cell immune response, proliferation and
      metastasis. Understanding the novel function orchestrating inflammation and
      bladder cancer will hopefully provide us insights into their future clinical
      significance in preventing bladder carcinogenesis and progression.

PMID- 29191001
TI  - Hybrid imaging in Crohn's disease: from SPECT/CT to PET/MR and new image
      interpretation criteria.
AB  - Crohn's disease is a chronic relapsing disease characterized by mucosal
      inflammation, lymphocytes infiltration and fibrotic strictures. Usually, the
      assessment of location, extension, inflammatory activity and severity of
      intestinal lesions is complex and invasive with endoscopic methods or
      histological and biochemical investigations. Thus, the diagnosis remains a
      challenge for the management of patients. Nuclear medicine techniques, in
      particular hybrid and molecular imaging, might offer a valid option for the
      evaluation and determination of the prognosis of the disease. Indeed, imaging
      methods provide a non-invasive, reproducible and quantitative analysis. An
      overview of the currently available multimodality imaging techniques in Crohn's
      disease are reviewed, with particular regard to positron-emission
      tomography/magnetic resonance and the choice of the best evaluation Score,
      explaining advantages and disadvantages of each one, with particular regard to
      their potential role for the assessment of disease activity and extent of
      inflammation in order to improve the diagnosis. We propose new interpretation
      criteria for PET/MR images.

PMID- 29191002
TI  - Tailoring Natural Abenquines To Inhibit the Photosynthetic Electron Transport
      through Interaction with the D1 Protein in Photosystem II.
AB  - Abenquines are natural N-acetylaminobenzoquinones bearing amino acid residues,
      which act as weak inhibitors of the photosynthetic electron transport chain.
      Aiming to exploit the abenquine scaffold as a model for the synthesis of new
      herbicides targeting photosynthesis, 14 new analogues were prepared by replacing
      the amino acid residue with benzylamines and the acetyl with different acyl
      groups. The synthesis was accomplished in three steps with a 68-95% overall yield
      from readily available 2,5-dimethoxyaniline, acyl chlorides, and benzyl amines.
      Key steps include (i) acylation of the aniline, (ii) oxidation, and (iii)
      oxidative addition of the benzylamino moiety. The compounds were assayed for
      their activity as Hill inhibitors, under basal, uncoupled, or phosphorylating
      conditions, or excluding photosystem I. Four analogues showed high effectiveness
      (IC50 = 0.1-0.4 MUM), comparable with the commercial herbicide diuron (IC50 = 0.3
      MUM). The data suggest that this class of compounds interfere at the reducing
      side of photosystem II, having protein D1 as the most probable target. Molecular
      docking studies with the plastoquinone binding site of Spinacia oleracea further
      strengthened this proposal.

PMID- 29191003
TI  - Enhanced Gas Separation through Nanoconfined Ionic Liquid in Laminated MoS2
      Membrane.
AB  - Two-dimensional (2D) materials-based membranes show great potential for gas
      separation. Herein an ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate
      ([BMIM][BF4]), was confined in the 2D channels of MoS2-laminated membranes via an
      infiltration process. Compared with the corresponding bulk [BMIM][BF4],
      nanoconfined [BMIM][BF4] shows an obvious incremental increase in freezing point
      and a shift of vibration bands. The resulting MoS2-supported ionic liquid
      membrane (MoS2 SILM) exhibits excellent CO2 separation performance with high CO2
      permeance (47.88 GPU) and superb selectivity for CO2/N2 (131.42), CO2/CH4
      (43.52), and CO2/H2 (14.95), which is much better than that of neat [BMIM][BF4]
      and [BMIM][BF4]-based membranes. The outstanding performance of MoS2 SILMs is
      attributed to the nanoconfined [BMIM][BF4], which enables fast transport of CO2.
      Long-term operation also reveals the durability and stability of the prepared
      MoS2 SILMs. The method of confining ILs in the 2D nanochannels of 2D materials
      may pave a new way for CO2 capture and separation.

PMID- 29191004
TI  - Wrinkle-Free Single-Crystal Graphene Wafer Grown on Strain-Engineered Substrates.
AB  - Wrinkles are ubiquitous for graphene films grown on various substrates by
      chemical vapor deposition at high temperature due to the strain induced by
      thermal mismatch between the graphene and substrates, which greatly degrades the
      extraordinary properties of graphene. Here we show that the wrinkle formation of
      graphene grown on Cu substrates is strongly dependent on the crystallographic
      orientations. Wrinkle-free single-crystal graphene was grown on a wafer-scale
      twin-boundary-free single-crystal Cu(111) thin film fabricated on sapphire
      substrate through strain engineering. The wrinkle-free feature of graphene
      originated from the relatively small thermal expansion of the Cu(111) thin film
      substrate and the relatively strong interfacial coupling between Cu(111) and
      graphene, based on the strain analyses as well as molecular dynamics simulations.
      Moreover, we demonstrated the transfer of an ultraflat graphene film onto target
      substrates from the reusable single-crystal Cu(111)/sapphire growth substrate.
      The wrinkle-free graphene shows enhanced electrical mobility compared to graphene
      with wrinkles.

PMID- 29191005
TI  - Construction of High Drug Loading and Enzymatic Degradable Multilayer Films for
      Self-Defense Drug Release and Long-Term Biofilm Inhibition.
AB  - Bacterial infections and biofilm formation on the surface of implants are
      important issues that greatly affect biomedical applications and even cause
      device failure. Construction of high drug loading systems on the surface and
      control of drug release on-demand is an efficient way to lower the development of
      resistant bacteria and biofilm formation. In the present study,
      (montmorillonite/hyaluronic acid-gentamicin)10 ((MMT/HA-GS)10) organic/inorganic
      hybrid multilayer films were alternately self-assembled on substrates. The
      loading dosage of GS was as high as 0.85 mg/cm2, which could be due the high
      specific surface area of MMT. The obtained multilayer film with high roughness
      gradually degraded in hyaluronidase (HAS) solutions or a bacterial infection
      microenvironment, which caused the responsive release of GS. The release of GS
      showed dual enzyme and bacterial infection responsiveness, which also indicated
      good drug retention and on-demand self-defense release properties of the
      multilayer films. Moreover, the GS release responsiveness to E. coli showed
      higher sensitivity than that to S. aureus. There was only ~5 wt % GS release from
      the film in PBS after 48 h of immersion, and the amount quickly increased to 30
      wt % in 105 CFU/mL of E. coli. Importantly, the high drug dosage, smart drug
      release, and film peeling from the surface contributed to the efficient
      antibacterial properties and long-term biofilm inhibition functions. Both in
      vitro and in vivo antibacterial tests indicated efficient sterilization function
      and good mammalian cell and tissue compatibility.

PMID- 29191007
TI  - Intracellularly Actuated Quantum Dot-Peptide-Doxorubicin Nanobioconjugates for
      Controlled Drug Delivery via the Endocytic Pathway.
AB  - Nanoparticle (NP)-mediated drug delivery (NMDD) has emerged as a novel method to
      overcome the limitations of traditional systemic delivery of therapeutics,
      including the controlled release of the NP-associated drug cargo. Currently, our
      most advanced understanding of how to control NP-associated cargos is in the
      context of soft nanoparticles (e.g., liposomes), but less is known about
      controlling the release of cargos from the surface of hard NPs (e.g., gold NPs).
      Here we employ a semiconductor quantum dot (QD) as a prototypical hard NP
      platform and use intracellularly triggered actuation to achieve spatiotemporal
      control of drug release and modulation of drug efficacy. Conjugated to the QD are
      two peptides: (1) a cell-penetrating peptide (CPP) that facilitates uptake of the
      conjugate into the endocytic pathway and (2) a display peptide conjugated to
      doxorubicin (DOX) via three different linkages (ester, disulfide, and hydrazone)
      that are responsive to enzymatic cleavage, reducing conditions, and low pH,
      respectively. Formation of the QD-[peptide-DOX]-CPP complex is driven by self
      assembly that allows control over both the ratio of each peptide species
      conjugated to the QD and the eventual drug dose delivered to cells. Forster
      resonance energy transfer assays confirmed successful assembly of the QD-peptide
      complexes and functionality of the linkages. Confocal microscopy was employed to
      visualize residence of the QD-[peptide-DOX]-CPP complexes in the endocytic
      pathway, and distinct differences in DOX localization were noted for the ester
      linkage, which showed clear signs of nuclear delivery versus the hydrazone,
      disulfide, and amide control. Finally, delivery of the QD-[peptide-DOX]-CPP
      conjugate resulted in cytotoxicity for the ester linkage that was comparable to
      free DOX. Attachment of DOX via the hydrazone linkage facilitated intermediary
      toxicity, while the disulfide and amide control linkages showed minimal toxicity.
      Our data demonstrate the utility of hard NP-peptide bioconjugates to function as
      multifunctional scaffolds for simultaneous control over cellular drug uptake and
      toxicity and the vital role played by the nature of the chemical linkage that
      appends the drug to the NP carrier.

PMID- 29191006
TI  - Selective and Mechanically Robust Sensors for Electrochemical Measurements of
      Real-Time Hydrogen Peroxide Dynamics in Vivo.
AB  - Hydrogen peroxide (H2O2) is an endogenous molecule that plays several important
      roles in brain function: it is generated in cellular respiration, serves as a
      modulator of dopaminergic signaling, and its presence can indicate the upstream
      production of more aggressive reactive oxygen species (ROS). H2O2 has been
      implicated in several neurodegenerative diseases, including Parkinson's disease
      (PD), creating a critical need to identify mechanisms by which H2O2 modulates
      cellular processes in general and how it affects the dopaminergic nigrostriatal
      pathway, in particular. Furthermore, there is broad interest in selective
      electrochemical quantification of H2O2, because it is often enzymatically
      generated at biosensors as a reporter for the presence of nonelectroactive target
      molecules. H2O2 fluctuations can be monitored in real time using fast-scan cyclic
      voltammetry (FSCV) coupled with carbon-fiber microelectrodes. However, selective
      identification is a critical issue when working in the presence of other
      molecules that generate similar voltammograms, such as adenosine and histamine.
      We have addressed this problem by fabricating a robust, H2O2-selective electrode.
      1,3-Phenylenediamine (mPD) was electrodeposited on a carbon-fiber microelectrode
      to create a size-exclusion membrane, rendering the electrode sensitive to H2O2
      fluctuations and pH shifts but not to other commonly studied neurochemicals. The
      electrodes are described and characterized herein. The data demonstrate that this
      technology can be used to ensure the selective detection of H2O2, enabling
      confident characterization of the role this molecule plays in normal
      physiological function as well as in the progression of PD and other neuropathies
      involving oxidative stress.

PMID- 29191008
TI  - Biomimetic Synthesis of Isorosmanol and Przewalskin A.
AB  - Przewalskin A, a novel C23 terpenoid with anti-HIV-1 activity from Salvia
      przewalskii Maxim, was formed in 10 steps via isorosmanol from (+)-carnosic acid.
      The synthetic strategy was inspired primarily by the biogenetic hypothesis and
      was enabled by epoxidation, epoxide ring opening, and lactonization in one pot to
      prepare the 11,12-dimethoxy isorosmanol, and bismuthonium ylide-induced ring
      expansion of o-quinone to construct the 2-acyl-3-hydroxytropone.

PMID- 29191009
TI  - Prediction of Broad-Spectrum Pathogen Attachment to Coating Materials for
      Biomedical Devices.
AB  - Bacterial infections in healthcare settings are a frequent accompaniment to both
      routine procedures such as catheterization and surgical site interventions. Their
      impact is becoming even more marked as the numbers of medical devices that are
      used to manage chronic health conditions and improve quality of life increases.
      The resistance of pathogens to multiple antibiotics is also increasing, adding an
      additional layer of complexity to the problems of employing safe and effective
      medical procedures. One approach to reducing the rate of infections associated
      with implanted and indwelling medical devices is the use of polymers that resist
      the formation of bacterial biofilms. To significantly accelerate the discovery of
      such materials, we show how state of the art machine learning methods can
      generate quantitative predictions for the attachment of multiple pathogens to a
      large library of polymers in a single model for the first time. Such models
      facilitate design of polymers with very low pathogen attachment across different
      bacterial species that will be candidate materials for implantable or indwelling
      medical devices such as urinary catheters, cochlear implants, and pacemakers.

PMID- 29191010
TI  - Design of a Temperature-Responsive Transcription Terminator.
AB  - RNA structures regulate various steps in gene expression. Transcription in
      bacteria is typically terminated by stable hairpin structures. Translation
      initiation can be modulated by metabolite- or temperature-sensitive RNA
      structures, called riboswitches or RNA thermometers (RNATs), respectively. RNATs
      control translation initiation by occlusion of the ribosome binding site at low
      temperatures. Increasing temperatures destabilize the RNA structure and
      facilitate ribosome access. In this study, we exploited temperature-responsive
      RNAT structures to design regulatory elements that control transcription
      termination instead of translation initiation in Escherichia coli. In order to
      mimic the structure of factor-independent intrinsic terminators, naturally
      occurring RNAT hairpins were genetically engineered to be followed by a U
      stretch. Functional temperature-responsive terminators (thermoterms) prevented
      mRNA synthesis at low temperatures but resumed transcription after a temperature
      upshift. The successful design of temperature-controlled terminators highlights
      the potential of RNA structures as versatile gene expression control elements.

PMID- 29191011
TI  - Use of Lentinan To Control Sharp Eyespot of Wheat, and the Mechanism Involved.
AB  - Lentinan (LNT), a complex polysaccharide with a beta-(1->3)-linked backbone of d
      glucose residues, has been reported to inhibit plant diseases. Our objective was
      to explore the efficacy and action mechanism of LNT used as a seed dressing to
      control sharp eyespot of wheat. Seed dressing promoted wheat growth. At control
      germination rates of 50%, 8 g of LNT/100 kg of seeds of the Jimai 22, Shannong
      23, and Luyuan 502 cultivars significantly increased seed germination to 54%,
      52%, and 51%, respectively. Seven days after emergence, the heights and root
      activity of wheat treated with LNT were significantly greater than those of
      controls. These effects were dose-dependent. At this time, the plant heights of
      Jimai 22, Shannong 23, and Luyuan 502 cultivars were 9.52, 8.52, and 10.52 cm,
      respectively, significantly higher than that of the controls. LNT prevented the
      development of wheat sharp eyespot. In the highly susceptible Jimai 22 cultivar,
      sharp eyespot development was reduced by 33.7%, 31.9%, and 30.4% at 7, 14, and 21
      days after germination. LNT somewhat increased phenylalanine ammonia-lyase,
      peroxidase, and superoxide dismutase activity; reduced the malondialdehyde
      content; increased chlorophyll a and b levels; and enhanced the root vigor of
      wheat. These effects peaked 7 days after germination. LNT increased transcription
      of the genes encoding alternative oxidase (AOX) and beta-1,3-glucanase (GLU), the
      salicylic acid signaling pathway-related gene NbPR1a, and the sharp eyespot
      resistance-related gene RS33. A significant dose-effect relationship was evident
      in terms of AOX transcription; we thus speculate that AOX may be the target gene.

PMID- 29191012
TI  - Tape-Assisted Photolithographic-Free Microfluidic Chip Cell Patterning for Tumor
      Metastasis Study.
AB  - Cancer metastatic dissemination is a complex event during tumor progression which
      involves cell-cell and cell-matrix interactions. Micropatterning is one of the
      most efficient ways to study tumor development because it can tune the
      distribution of cells with spatial and temporal control. Extensive studies have
      shown that microfluidics can provide a feasible method for cell patterning.
      However, the current technique requires a microfabrication laboratory to
      manufacture the chip, which results in inaccessibility to researchers, especially
      biologists who focus on disclosing biological mechanisms rather than the methods.
      In this work, we developed a new methodology (tape-assisted photolithographic
      free microfluidic chip, TAPMiC) that can realize homogeneous and heterogeneous
      micropatterning (45 features, 300 MUm diameter of each) on a culture dish without
      the photolithographic procedure. We have applied this method to study critical
      biological problems, such as tumor cell migration under different conditions,
      including antitumor pharmaceutics and candidate gene RNAi assay that was relevant
      to tumor translocation and invasion. Moreover, this platform can achieve
      copatterning to recapitulate the tumor invasion scenario with single-cell
      trackable analysis. To decode regulation during metastasis, we conducted in situ
      recovering for quantitative polymerase chain reaction (qPCR) analysis from each
      cell type from tumor-fibroblast copairing. Regulation of several essential genes
      has unveiled that matrix degradation gene MMP2 and angiogenesis associated gene
      VEGFA were up-regulated in tumor cells in the fibroblast-enriched niche compared
      with homogeneous cultivation. Therefore, this approach constitutes a novel tool
      for investigating metastasis with quantitative measurements both on phenotype and
      genetical information.

PMID- 29191013
TI  - Multiscale Molecular Dynamics Approach to Energy Transfer in Nanomaterials.
AB  - After local transient fluctuations are dissipated, in an energy transfer process,
      a system evolves to a state where the energy density field varies slowly in time
      relative to the dynamics of atomic collisions and vibrations. Furthermore, the
      energy density field remains strongly coupled to the atomic scale processes
      (collisions and vibrations), and it can serve as the basis of a multiscale theory
      of energy transfer. Here, a method is introduced to capture the long scale energy
      density variations as they coevolve with the atomistic state in a way that yields
      insights into the basic physics and implies an efficient algorithm for energy
      transfer simulations. The approach is developed based on the N-atom Liouville
      equation and an interatomic force field and avoids the need for conjectured
      phenomenological equations for energy transfer and other processes. The theory is
      demonstrated for sodium chloride and silicon dioxide nanoparticles immersed in a
      water bath via molecular dynamics simulations of the energy transfer between a
      nanoparticle and its aqueous host fluid. The energy density field is computed for
      different sets of symmetric grid densities, and the multiscale theory holds when
      slowly varying energy densities at the nodes are obtained. Results strongly
      depend on grid density and nanoparticle constituent material. A nonuniform
      temperature distribution, larger thermal fluctuations in the nanoparticle than in
      the bath, and enhancement of fluctuations at the surface, which are expressed due
      to the atomic nature of the systems, are captured by this method rather than by
      phenomenological continuum energy transfer models.

PMID- 29191014
TI  - Pyrrolidone Modification Prevents PAMAM Dendrimers from Activation of Pro
      Inflammatory Signaling Pathways in Human Monocytes.
AB  - The biological features of dendrimers are affected by the character of highly
      reactive terminal moieties. In some polyamine dendrimer types the surface charge
      makes them bioincompatible and prevent their direct medical application.
      Moreover, foreign particles can induce the immune response which is undesirable
      due to the adverse side effects in vivo. The reduction of cytotoxicity of
      positively charged macromolecules is possible through chemical modifications of
      terminal groups. In our study, we have developed new derivatives of PAMAM
      dendrimers modified with 4-carbomethoxypyrrolidone and evaluated their
      immunomodulatory properties. The experiments were conducted on two human cancer
      myeloid cell lines: THP-1 and U937. To evaluate the cytotoxicity of dendrimers,
      the reasazurin assay was applied. The expression level of NF-kappaB targets
      (NFKBIA, BTG2) and cytokine genes (IL1B, TNF) was determined by quantitative real
      time RT-PCR. The measurement of binding of NF-kappaB to a consensus DNA probe was
      determined by electrophoretic mobility shift assay. The ELISA cytokine assay was
      performed to measure protein concentration of IL-1beta and TNFalpha. We have
      found that PAMAM-pyrrolidone dendrimers did not impact THP-1 and U937 viability
      even at high concentrations (up to 200 MUM). The surface modification prevented
      PAMAM dendrimers from stimulating NF-kappaB-related signal transduction, which
      have been determined on the level of nuclear translocation, gene expression and
      protein secretion. Pyrrolidone modification efficiently prevents PAMAM dendrimers
      from stimulating pro-inflammatory response in human cancer myeloid cell lines,
      thus it can be used to improve the biocompatibility of positively charged
      dendrimers and to broaden the scope of their biological applications.

PMID- 29191015
TI  - Dynamics Sampling in Transition Pathway Space.
AB  - The minimum energy pathway contains important information describing the
      transition between two states on a potential energy surface (PES). Chain-of
      states methods were developed to efficiently calculate minimum energy pathways
      connecting two stable states. In the chain-of-states framework, a series of
      structures are generated and optimized to represent the minimum energy pathway
      connecting two states. However, multiple pathways may exist connecting two
      existing states and should be identified to obtain a full view of the
      transitions. Therefore, we developed an enhanced sampling method, named as the
      direct pathway dynamics sampling (DPDS) method, to facilitate exploration of a
      PES for multiple pathways connecting two stable states as well as addition minima
      and their associated transition pathways. In the DPDS method, molecular dynamics
      simulations are carried out on the targeting PES within a chain-of-states
      framework to directly sample the transition pathway space. The simulations of
      DPDS could be regulated by two parameters controlling distance among states along
      the pathway and smoothness of the pathway. One advantage of the chain-of-states
      framework is that no specific reaction coordinates are necessary to generate the
      reaction pathway, because such information is implicitly represented by the
      structures along the pathway. The chain-of-states setup in a DPDS method greatly
      enhances the sufficient sampling in high-energy space between two end states,
      such as transition states. By removing the constraint on the end states of the
      pathway, DPDS will also sample pathways connecting minima on a PES in addition to
      the end points of the starting pathway. This feature makes DPDS an ideal method
      to directly explore transition pathway space. Three examples demonstrate the
      efficiency of DPDS methods in sampling the high-energy area important for
      reactions on the PES.

PMID- 29191016
TI  - Room-Temperature Mid-Infrared Emission from Faceted InAsSb Multi Quantum Wells
      Embedded in InAs Nanowires.
AB  - There is considerable interest in the development of InAsSb-based nanowires for
      infrared photonics due to their high tunability across the infrared spectral
      range, high mobility, and integration with silicon electronics. However, optical
      emission is currently limited to low temperatures due to strong nonradiative
      Auger and surface recombination. Here, we present a new structure based on
      conical type II InAsSb/InAs multiquantum wells within InAs nanowires which
      exhibit bright mid-infrared photoluminescence up to room temperature. The
      nanowires are grown by catalyst-free selective area epitaxy on silicon. This
      unique geometry confines the electron-hole recombination to within the quantum
      wells which alleviates the problems associated with recombination via surface
      states, while the quantum confinement of carriers increases the radiative
      recombination rate and suppresses Auger recombination. This demonstration will
      pave the way for the development of new integrated quantum light sources
      operating in the technologically important mid-infrared spectral range.

PMID- 29191017
TI  - Development of Antifouling Hyperbranched Polyglycerol Layers on Hydroxyl Poly-p
      xylylene Coatings.
AB  - Antifouling surfaces that are resistant to protein adsorption and cell adhesion
      are desirable for many biomedical devices, such as diagnostic devices,
      biosensors, and implants. In this study, we developed an antifouling
      hyperbranched polyglycerol (hPG) surface on hydroxyl poly-p-xylylene (PPX-OH).
      PPX-OH was deposited via chemical vapor deposition (CVD), and an hPG film was
      then developed via the ring-opening reaction of glycidol. The hPG film greatly
      reduced the adhesion of L929 cells and platelets as well as protein adsorption.
      The addition of alkenyl groups in the hPG layer allows the conjugation of
      biomolecules, such as peptides and biotin, and elicits specific biological
      interactions. Since the CVD deposition of PPX-OH could be applied to most types
      of materials, our approach makes it possible to decorate an antifouling hPG film
      on most types of materials. Our method could be applied to biosensors,
      diagnostics, and biomedical devices in the future.

PMID- 29191018
TI  - Production of N2O5 and ClNO2 through Nocturnal Processing of Biomass-Burning
      Aerosol.
AB  - Biomass burning is a source of both particulate chloride and nitrogen oxides, two
      important precursors for the formation of nitryl chloride (ClNO2), a source of
      atmospheric oxidants that is poorly prescribed in atmospheric models. We
      investigated the ability of biomass burning to produce N2O5(g) and ClNO2(g)
      through nocturnal chemistry using authentic biomass-burning emissions in a smog
      chamber. There was a positive relationship between the amount of ClNO2 formed and
      the total amount of particulate chloride emitted and with the chloride fraction
      of nonrefractory particle mass. In every fuel tested, dinitrogen pentoxide (N2O5)
      formed quickly, following the addition of ozone to the smoke aerosol, and
      ClNO2(g) production promptly followed. At atmospherically relevant relative
      humidities, the particulate chloride in the biomass-burning aerosol was rapidly
      but incompletely displaced, likely by the nitric acid produced largely by the
      heterogeneous uptake of N2O5(g). Despite this chloride acid displacement, the
      biomass-burning aerosol still converted on the order of 10% of reacted N2O5(g)
      into ClNO2(g). These experiments directly confirm that biomass burning is a
      potentially significant source of atmospheric N2O5 and ClNO2 to the atmosphere.

PMID- 29191019
TI  - Affinity of Ketamine to Clinically Relevant Transporters.
AB  - Ketamine is a widely used intravenous anesthetic drug that has also a pronounced
      analgesic effect. Moreover, one of its metabolites was very recently shown to
      possess antidepressant activity. Consequently, oral administration of ketamine
      may become of interest in the future. There is evidence from in vitro data, drug
      drug interactions, and the physicochemical properties of the drug that ketamine
      may be a substrate of drug transporters. Thus, it was the aim of this study to
      investigate the affinity of ketamine to clinically relevant transporter proteins
      that are expected to affect its intestinal absorption, distribution, and
      excretion. Ketamine was shown to be significantly taken up in a time- and
      concentration-dependent manner by OCT1-3. The affinity to OCT transporters at pH
      6.5 (Km ~ 35-75 MUM) was clearly higher than that at pH 7.4. In addition,
      ketamine permeability was markedly lower at pH 6.5 than at pH 7.4 in a parallel
      artificial membrane permeability assay (PAMPA). Ketamine showed a low but
      significant affinity to P-gp at pH 6.5. In contrast to this, we could not detect
      any transport of ketamine by MATE1/2K. In conclusion, ketamine is a substrate for
      OCT1-3 and P-gp but is not recognized by MATE1/2K. Considering that ketamine is a
      lipophilic base that mainly exists as a cationic moiety (>90%) in the intestinal
      lumen, we conclude that the OCT-mediated cellular uptake as well as P-gp efflux
      is expected to be only of relevance in the human intestine (i.e., in the case of
      oral drug administration), where OCT1, OCT3, and P-gp are stably expressed at the
      apical membrane. On the other side, P-gp is not expected to contribute
      significantly to tissue (brain) distribution or renal excretion of ketamine.

PMID- 29191021
TI  - Dealkanative Main Group Couplings across the peri-Gap.
AB  - Here, we highlight the ability of peri-substitution chemistry to promote a series
      of unique P-P/P-As coupling reactions, which proceed with concomitant C-H bond
      formation. This dealkanative reactivity represents an interesting and unexpected
      expansion to the established family of main-group dehydrocoupling reactions.
      These transformations are exceptionally clean, proceeding essentially
      quantitatively at relatively low temperatures (70-140  degrees C), with 100%
      diastereoselectivity in the products. The reaction appears to be radical in
      nature, with the addition of small quantities of a radical initiator
      (azobis(isobutyronitrile)) increasing the rate dramatically, as well as altering
      the apparent order of reaction. DFT calculations suggest that the reaction
      involves dissociation of a phosphorus centered radical (stabilized by the peri
      backbone) to the P-P coupled product and a free propyl radical, which carries the
      chain. This unusual reaction demonstrates the powerful effect that geometric
      constraints, in this case a rigid scaffold, can have on the reactivity of main
      group species, an area of research that is gaining increasing prominence in
      recent years.

PMID- 29191020
TI  - Highly Tunable Electronic Structures of Phosphorene/Carbon Nanotube
      Heterostructures through External Electric Field and Atomic Intercalation.
AB  - Black phosphorene (BP)/carbon nanotube (CNT) heterostructures can be classified
      as either type I or II, depending on the size of the CNTs. An external electric
      field (Eext) can modulate the interfacial electronic structures and separate the
      electron and hole carriers of the BP/CNT heterostructures. The giant Stark effect
      is observed, and the band gap of the semiconducting heterostructures can vary
      several-fold. The intercalation of 3d transition metals can strongly bond BP and
      CNTs together. Furthermore, strong ferromagnetism with Curie temperature (TC)
      above room temperature is predicted. It is expected that these BP/CNT
      heterostructures will provide new opportunities and applications in the fields of
      optoelectronics and electronics as well as spintronics.

PMID- 29191022
TI  - Phonon-Driven Oscillatory Plasmonic Excitonic Nanomaterials.
AB  - We demonstrate that coherent acoustic phonons derived from plasmonic
      nanoparticles can modulate electronic interactions with proximal excitonic
      molecular species. A series of gold bipyramids with systematically varied aspect
      ratios and corresponding localized surface plasmon resonance energies,
      functionalized with a J-aggregated thiacarbocyanine dye molecule, produces two
      hybridized states that exhibit clear anticrossing behavior with a Rabi splitting
      energy of 120 meV. In metal nanoparticles, photoexcitation generates coherent
      acoustic phonons that cause oscillations in the plasmon resonance energy. In the
      coupled system, these photogenerated oscillations alter the metal nanoparticle's
      energetic contribution to the hybridized system and, as a result, change the
      coupling between the plasmon and exciton. We demonstrate that such modulations in
      the hybridization are consistent across a wide range of bipyramid ensembles. We
      also use finite-difference time domain calculations to develop a simple model
      describing this behavior. Such oscillatory plasmonic-excitonic nanomaterials
      offer a route to manipulate and dynamically tune the interactions of
      plasmonic/excitonic systems and unlock a range of potential applications.

PMID- 29191023
TI  - Rapidly Activating Pd-Precatalyst for Suzuki-Miyaura and Buchwald-Hartwig
      Couplings of Aryl Esters.
AB  - Esters are valuable electrophiles for cross-coupling due to their ubiquity and
      ease of synthesis. However, harsh conditions are traditionally required for the
      effective cross-coupling of ester substrates. Utilizing a recently discovered
      precatalyst, Pd-catalyzed Suzuki-Miyaura and Buchwald-Hartwig reactions involving
      cleavage of the C(acyl)-O bond of aryl esters that proceed under mild conditions
      are reported. The Pd(II) precatalyst is highly active because it is reduced to
      the Pd(0) active species more rapidly than previous precatalysts.

PMID- 29191024
TI  - Pretargeted PET Imaging Using a Bioorthogonal 18F-Labeled trans-Cyclooctene in an
      Ovarian Carcinoma Model.
AB  - In cancer research, pretargeted positron emission tomography (PET) imaging has
      emerged as an effective two-step approach that combines the excellent target
      affinity and selectivity of antibodies with the advantages of using short-lived
      radionuclides such as fluorine-18. One possible approach is based on the
      bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) reaction between
      tetrazines and trans-cyclooctene (TCO) derivatives. Here, we report the first
      successful use of an 18F-labeled small TCO compound, [18F]1 recently developed in
      our laboratory, to perform pretargeted immuno-PET imaging. The study was
      performed in an ovarian carcinoma mouse model, using a trastuzumab-tetrazine
      conjugate.

PMID- 29191025
TI  - Progress and Future Direction of Chromosome-Centric Human Proteome Project.
AB  - This special issue of JPR celebrates the fifth anniversary of the Chromosome
      Centric Human Proteome Project (C-HPP). We present 27 manuscripts in four
      categories: (i) Metrics of Progress and Resources, (ii) Missing Protein Detection
      and Validation, (iii) Analytical Methods and Quality Assessment, and (iv) Protein
      Functions and Disease. We briefly introduce key messages from each paper, mostly
      from C-HPP teams and some from the Biology and Disease-driven HPP. From the first
      few months of the C-HPP NeXt-MP50 Missing Proteins Challenge, authors report 73
      missing protein detections that meet the HPP guidelines using several novel
      approaches. Finally, we discuss future directions.

PMID- 29191027
TI  - Firearms Policy and Suicide Prevention.

PMID- 29191029
TI  - Facilitating Temporary, Safe Firearms Restrictions Among Individuals at High Risk
      of Suicide: Response to Sung.

PMID- 29191030
TI  - Altered Sensory Phenomena Experienced in Bipolar Disorder.

PMID- 29191031
TI  - BDNF, 5-HT, and Anxiety: Identification of a Critical Periadolescent
      Developmental Period.

PMID- 29191032
TI  - 2017 in Review.

PMID- 29191033
TI  - Joan of Arc-Hearing Voices.

PMID- 29191034
TI  - CORRECTION.

PMID- 29191035
TI  - Epigenetic Programming: A Putative Neurobiological Mechanism Linking Childhood
      Maltreatment and Risk for Adult Psychopathology.

PMID- 29191036
TI  - Gender Minority Stress, Depression, and Anxiety in a Transgender High School
      Student.

PMID- 29191038
TI  - Disability Enrollment in a Community-Based Coordinated Specialty Care Program.

PMID- 29191039
TI  - Frontal Lobe Moderators and Mediators of Response to Exposure Therapy in PTSD.

PMID- 29191040
TI  - The War on Terror: Is There Ever Room for Compassion?

PMID- 29191041
TI  - New butyrolactone and other metabolites from the bark of Endlicheria arenosa
      against of the phytopathogen Colletotrichum tamarilloi.
AB  - In this work, screening of Lauraceae species for their antifungal activity
      against Collectotrichum tamarilloi was carried out and the ethanol extract
      derived from the bark of Endlicheria arenosa was found to be the best candidate.
      From the ethanolic extract of the bark of E. arenosa, the hexane and chloroform
      fractions were found to be active, from these five fatty acids were identified
      and two lactones were isolated. The most active fatty acid was the dodecanoic
      acid with a minimal inhibitory concentration (MIC) of 78.0 MUM. The butyrolactone
      3R,4R-licunolide A, it has not previously reported, and licunolide B show both
      the lowest MIC (55.3 MUM). This is the first report of compounds of natural
      origin as growth inhibitors of C. tamarilloi.

PMID- 29191042
TI  - Optimization on biodistribution and antitumor activity of tripterine using
      polymeric nanoparticles through RES saturation.
AB  - Systemic delivery of tripterine (TPR) is challenged by its insoluble property and
      unsuitable pharmacokinetics. This work aimed to develop polymeric nanoparticles
      (NPs) combined with the reticuloendothelial system (RES) saturation to improve
      the in vivo distribution and antitumor activity of TPR. TPR-loaded nanoparticles
      (TPR-NPs) were prepared by the low-energy emulsification/evaporation method and
      characterized with particle size, entrapment efficiency, and morphology. The
      resulting TPR-NPs were 75 nm around in particle size and displayed a sustained
      drug release in pH 7.4 medium. Pharmacokinetic studies revealed that TPR-NPs had
      the advantage in bettering the pharmacokinetic properties of TPR over the
      solution formulation. However, the ameliorative effect on pharmacokinetics was
      more significant in the case of RES saturation (i.e. preinjection of blank NPs).
      Preinjection of blank NPs followed by injection of TPR-NPs resulted in higher
      distribution of TPR into the tumor due to reduced sequestration of TPR-NPs by
      RES. In tumor-bearing mice (prostatic cancer model), TPR-NPs treatment with RES
      saturation exhibited a superior antitumor efficacy to free TPR and TPR-NPs alone.
      It can be concluded that formulating TPR into polymeric NPs in combination with
      RES saturation is an effective means to address the systemic delivery of TPR.

PMID- 29191044
TI  - ALSUntangled 43: copper.

PMID- 29191043
TI  - What does the future hold for novel intravascular imaging devices: a focus on
      morphological and physiological assessment of plaque.
AB  - INTRODUCTION: It is well recognized that a lesion that does not cause a
      hemodynamically significant stenosis can trigger a sudden cardiac event through
      plaque rupture. As a diagnostic tool, intravascular imaging was developed to
      circumvent limitations of coronary angiography; however, none of the
      intravascular imaging devices are individually able to provide complete
      assessment of the plaque morphology, geometry, physiology and biology. Therefore,
      over the past few years an effort was made to develop hybrid intravascular
      imaging catheters to provide more complete evaluation of coronary plaque
      pathobiology. Areas covered: This paper aims to give an overview of the recent
      developments on 1) single-modality intravascular imaging devices; 2) hybrid
      intravascular imaging devices and 3) the hemodynamic analysis in models
      reconstructed from the fusion of intravascular imaging and angiographic data.
      Expert commentary: Within five years, most of the hybrid imaging techniques which
      are now in pre-clinical phase will be utilized in the clinical arena, as NIRS
      IVUS. Software for online blood simulation is likely to be developed that will
      enable ESS calculation while the patient is in the catheterization laboratory.

PMID- 29191045
TI  - Corrigendum.
AB  - Marks DF (2017) Special issue on the PACE Trial. Journal of Health Psychology
      22(9): 1103-1105. DOI: 10.1177/1359105317722370. In the above referenced
      editorial, direct quotations from editorial correspondence had been included
      without permission for publication on page 1104. The online version of this
      editorial has now been corrected to remove these quotations.

PMID- 29191046
TI  - Cost-effectiveness associated with amyotrophic lateral sclerosis: some questions
      and answers pending.

PMID- 29191047
TI  - Stealth lipid polymer hybrid nanoparticles loaded with rutin for effective brain
      delivery - comparative study with the gold standard (Tween 80): optimization,
      characterization and biodistribution.
AB  - The blood-brain barrier is considered the leading physiological obstacle
      hindering the transport of neurotherapeutics to brain cells. The application of
      nanotechnology coupled with surfactant coating is one of the efficacious tactics
      overcoming this barrier. The aim of this study was to develop lipid polymer
      hybrid nanoparticles (LPHNPs), composed of a polymeric core and a phospholipid
      shell entangled, for the first time, with PEG-based surfactants (SAA) viz. TPGS
      or Solutol HS 15 in comparison with the gold standard Tween 80, aiming to enhance
      brain delivery and escape opsonization. LPHNPs were successfully prepared using
      modified single-step nanoprecipitation technique, loaded with the flavonoid rutin
      (RU), extracted from the flowers of Calendula officinalis L., and recently proved
      as a promising anti-Alzheimer. The effect of the critical process parameters
      (CPP) viz. PLGA amount, Wlecithin/WPLGA ratio, and Tween 80 concentration on
      critical quality attributes (CQA); entrapment, size and size distribution, was
      statistically analyzed via design of experiments, and optimized using the
      desirability function. The optimized CPP were maintained while substituting Tween
      80 with other PEG-SAA. All hybrid particles exhibited spherical shape with
      perceptible lipid shells. The biocompatibility of the prepared NPs was confirmed
      by hemolysis test. The pharmacokinetic assessments, post-intravenous
      administration to rats, revealed a significant higher RU bioavailability for NPs
      relative to drug solution. Biodistribution studies proved non-significant
      differences in RU accumulation within brain, but altered phagocytic uptake among
      various LPHNPs. The present study endorses the successful development of LPHNPs
      using PEG-SAA, and confirms the prospective applicability of TPGS and Solutol in
      enhancing brain delivery.

PMID- 29191048
TI  - Drug delivery vectors based on filamentous bacteriophages and phage-mimetic
      nanoparticles.
AB  - With the development of nanomedicine, a mass of nanocarriers have been exploited
      and utilized for targeted drug delivery, including liposomes, polymers,
      nanoparticles, viruses, and stem cells. Due to huge surface bearing capacity and
      flexible genetic engineering property, filamentous bacteriophage and phage
      mimetic nanoparticles are attracting more and more attentions. As a rod-like bio
      nanofiber without tropism to mammalian cells, filamentous phage can be easily
      loaded with drugs and directly delivered to the lesion location. In particular,
      chemical drugs can be conjugated on phage surface by chemical modification, and
      gene drugs can also be inserted into the genome of phage by recombinant DNA
      technology. Meanwhile, specific peptides/proteins displayed on the phage surface
      are able to conjugate with nanoparticles which will endow them specific-targeting
      and huge drug-loading capacity. Additionally, phage peptides/proteins can
      directly self-assemble into phage-mimetic nanoparticles which may be applied for
      self-navigating drug delivery nanovehicles. In this review, we summarize the
      production of phage particles, the identification of targeting peptides, and the
      recent applications of filamentous bacteriophages as well as their
      protein/peptide for targeting drug delivery in vitro and in vivo. The improvement
      of our understanding of filamentous bacteriophage and phage-mimetic nanoparticles
      will supply new tools for biotechnological approaches.

PMID- 29191049
TI  - Addiction to Internet Use, Online Gaming, and Online Social Networking Among
      Young Adults in China, Singapore, and the United States.
AB  - The current study investigated the rates of addictions to Internet use, online
      gaming, and online social networking as well as their associations with
      depressive symptoms among young adults in China, Singapore, and the United
      States. A total of 3267 undergraduate students were recruited. Psychological
      instruments were used to assess various Internet-related addictions and
      depressive symptoms. Male students were more addicted to Internet and online
      gaming whereas female students were more addicted to online social networking.
      Compared with students in the United States, Chinese and Singaporean students
      were more addicted to Internet use and online social networking but less to
      online gaming. The odds of depression among students with addiction to various
      Internet-related addictions were highest in China. Internet-related addiction is
      a new public health concern of young adults, especially in the Asia-Pacific
      regions. It is found to associate with depressive symptoms. Strategies should
      address this phenomenon with attention to specific needs of gender and region
      while managing mood disturbances.

PMID- 29191050
TI  - Isoprenylated phenolic compounds with tyrosinase inhibition from Morus nigra.
AB  - A new isoprenylated sanggenon-type flavanone, nigrasin K (1), together with three
      known analogs (2-4) and five known Diels-Alder adducts (5-9), were isolated from
      the twigs of Morus nigra. Their structures were elucidated by spectroscopic
      methods. Sanggenon M (2), chalcomoracin (5), sorocein H (6), kuwanon J (7),
      sanggenon C (8), and sanggenon O (9) showed significant inhibitory effects on
      mushroom tyrosinase.

PMID- 29191051
TI  - Preoperative evaluation of moyamoya spontaneous anastomosis of combined
      revascularization donor vessels in adults by duplex ultrasonography.
AB  - OBJECTIVE: To evaluate the preoperative diagnostic value of duplex
      ultrasonography in moyamoya spontaneous anastomosis of combined revascularization
      donor vessels in adults. METHODS: A total of 99 preoperative adult patients who
      underwent superficial temporal artery-to-middle cerebral artery (STA-MCA)
      anastomosis were retrospectively analyzed. Each side of the cerebral hemisphere
      was examined as a separate procedure. A total of 198 cerebral hemispheres were
      divided into three groups: a collateral, non-collateral, and control group based
      on digital subtraction angiography (DSA). Hemodynamic parameters, including peak
      systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI)
      were analyzed. RESULTS: There were only four of cases (5%, 4/198) of STA
      spontaneous anastomosis, whereas those of maxillary artery (MA) anastomosis were
      44 (23.7%, 44/186). Compared with the control group, MA PSV and EDV of the
      collateral group increased significantly, while RI decreased significantly (p <
      .05). The area under the curve (AUC) of MA RI was 0.654. As a predictor of MA
      spontaneous anastomosis, duplex ultrasonography had high specificity but poor
      sensitivity. In collateral group, PSV and EDV detected two weeks post-surgery
      were significantly higher than those detected pre-operatively (PSV: p = .018,
      EDV: p = .025). By contrast, there were no significant difference of the PSV and
      EDV detected six months post-surgery compared with pre-operation (PSV: p = .450,
      EDV: p = .099). Additionally, MA RI in two weeks after the surgery was comparable
      with preoperative values. CONCLUSIONS: Duplex ultrasonography could be applied to
      evaluate the adult moyamoya spontaneous anastomoses of MA preoperatively. Despite
      its poor sensitivity, this diagnostic modality is still reliable and specific.
      STA-MCA anastomosis combined with EDMS did not affect MA pre-operative
      spontaneous anastomosis.

PMID- 29191052
TI  - A randomized controlled trial of resistance and endurance exercise in amyotrophic
      lateral sclerosis.
AB  - OBJECTIVE: Evaluate the safety and tolerability of resistance and endurance
      exercise in ALS participants as measured by their ability to complete this six
      month study. METHODS: Participants were randomized to Resistance, Endurance, or
      Stretching/Range of Motion (SROM the exercise regimen prescribed for most ALS
      patients) exercises. All exercises were performed at home with an individualized
      regimen designed by a physical therapist trained in ALS management. Primary
      outcome measures were tolerability of the exercises at 24 weeks defined by 50% of
      participants completing at least 50% of the prescribed exercise regimen.
      Secondary outcome measures included the ALSFRS-R, pulmonary FVC, and other
      measures of ALS function. RESULTS: At 12 and 24 weeks, all three exercise
      regimens were tolerated according to our pre-specified criteria. Compliance to
      the prescribed exercise regimen was the highest in the resistance and SROM arms
      of the study. All three forms of exercise were considered safe as there were no
      differences in the rates of disease progression among groups. There were no
      differences in the secondary outcome measures and feasibility for evaluating
      these measures was successful. In a post-hoc analysis, there was a trend towards
      fewer falls in the Resistance and Endurance groups. CONCLUSIONS: This study
      demonstrates that SROM, resistance, and endurance exercise are all safe to be
      performed with the specified regimen without any worsening of outcomes as related
      to ALS function. All three forms of exercise were tolerated with resistance and
      SROM exercises showing the highest compliance over the 24 week-period.

PMID- 29191053
TI  - Diagnosis and Management of Conjunctivitis for the Dermatologist.
AB  - Atopic dermatitis is a chronic, sometimes relapsing inflammatory skin condition
      that presents with pruritus and characteristic skin manifestations.
      Conjunctivitis is a common ocular comorbidity affecting almost half of patients
      with the risk increasing with atopic dermatitis severity. Recent targeted
      biologic therapies that successfully treat atopic skin disease, including
      dupilumab, which blocks interleukin (IL)-4 and IL-13, as well as agents that
      block IL-13 alone, have been associated with an increased rate of conjunctivitis
      in clinical trials. Because conjunctivitis commonly occurs in patients with
      atopic dermatitis and as the treatment with targeted biologic agents may increase
      the risk or severity of conjunctivitis, it is important that dermatologists
      recognize symptoms, appreciate treatment options, and know when referral to an
      ophthalmologist is appropriate.

PMID- 29191054
TI  - Onychomycosis and Chronic Fungal Disease: Exploiting a Commensal Disguise to
      Stage a Covert Invasion.
AB  - Onychomycosis is a chronic fungal infection that is recalcitrant to treatment and
      often results in relapse. New evidence suggests that disease prognosis may be
      linked to pathogens manipulating host immune responses. Therefore, individuals
      with specific mutations, including those affecting pattern recognition receptors
      or the interleukin (IL)-17 and IL-22 pathways, may be more susceptible to
      infection. Moreover, it is recommended that those with a family history of immune
      mutations or predisposition to fungal disease be treated aggressively for
      onychomycosis prior to symptom progression. In addition, incorporating genetic
      testing and new investigational therapy such as IL-33 and interferon-gamma may
      improve treatment outcome.

PMID- 29191055
TI  - Recurrence after pulmonary vein isolation is associated with low contact force.
AB  - OBJECTIVES: Recurrent arrhythmia after pulmonary vein isolation (PVI) by
      radiofrequency (RF) ablation in patients with atrial fibrillation (AFIB) remains
      a significant challenge. Using contact force (CF) sensing ablation catheters, we
      aimed to identify procedure related parameters associated with recurrence after
      de-novo PVI in patients with AFIB. METHODS: Consecutive patients undergoing a de
      novo PVI procedure (n = 120, 63% paroxysmal and 37% persistent AFIB) employing a
      force-sensing ablation catheter were included. A clinical control including
      electrocardiogram and 120 hour of Holter-recording at 12-months was performed in
      all patients. Recurrence was defined as any documented AFIB or atrial flutter
      more than 30 seconds on Holter-recording after an initial blanking period of
      three months. RESULTS: Recurrence occurred in 44 patients (37%). Mean CF was
      lower in patients with recurrent arrhythmia (22.2 +/- 9.5 vs. 28.8 +/- 9.3 g, p <
      .001). In multi-variable analyses lower mean CF (OR 0.9 (95% CI 0.8-1.0), p =
      .03), and higher percentage of ablation time with a CF <10 grams (OR 1.1 (95% CI
      1.0-1.1), p = .004) were both associated with recurrence in two distinct models.
      Dragging during ablation compared with point-by-point ablation technique was
      associated with recurrence in both models (OR 19.2 (95% CI 2.9-130.0), p = .002,
      and OR 21.7 (95% CI 2.7-176.2), p = .004). CONCLUSIONS: Low CF and dragging
      during ablation as compared with point-by-point ablation technique were
      associated with recurrent arrhythmia in patients with AFIB undergoing de-novo PVI
      by RF ablation.

PMID- 29191056
TI  - Emotional distress and subjective impact of the disease in young women with
      breast cancer and their spouses.
AB  - AIM: Evaluate the influence of emotional distress of young women with breast
      cancer and their spouses on their daily subjective experience of the disease,
      through application of the Actor-Partner Interdependence Model. PATIENTS &
      METHODS: A total of 112 women under 45 years of age were diagnosed with
      nonmetastatic breast cancer and their spouses answered self-reported measures of
      anxiety, depression and subjective experience of the disease and its treatment.
      RESULTS: The patient's emotional distress influenced more the subjective
      experience of her spouse than the spouse's emotional distress influenced the
      patient. The spouse's difficulties depended as much on his own distress level as
      on the patient's distress level. CONCLUSION: These data confirm the importance of
      implementing couple-focused interventions.

PMID- 29191057
TI  - Co-delivery nanoparticles of anti-cancer drugs for improving chemotherapy
      efficacy.
AB  - To achieve superior therapeutic efficacy, the combination chemotherapy using two
      or more anticancer drugs in clinical practice has been generally accepted as a
      feasible strategy. On account of the concept of combination chemotherapy, co
      delivery of anticancer drugs with nanotechnology gradually becomes a desired
      strategy and one of the research frontiers on modern drug delivery. In recent
      years, nano drug co-delivery system (NDCDS), which loads at least two anticancer
      drugs with different physicochemical and pharmacological properties into a
      combination delivery system, has achieved rapid development. NDCDS
      synergistically inhibited the growth of the tumor compared with the free drugs.
      In this review, we highlighted the current state of co-delivery nanoparticles and
      the most commonly used nanomaterial, discussed challenges and strategies, and
      prospect future development.

PMID- 29191058
TI  - Nanoemulsion-based delivery system for enhanced oral bioavailability and caco-2
      cell monolayers permeability of berberine hydrochloride.
AB  - Berberine hydrochloride (BBH) has a variety of pharmacological activities such as
      antitumor, antimicrobial, anti-inflammation, and reduce irritable bowel syndrome.
      However, poor stability and low oral bioavailability limited its usage. Herein,
      an oil-in-water nanoemulsion system of BBH was developed to improve its stability
      and oral bioavailability. The pseudoternary phase diagrams were constructed for
      the determination of composition of various nanoemulsions. The nanoemulsions of
      BBH composed of Labrafil M 1944 CS (oil phase), RH-40 (surfactant), glycerin (co
      surfactant), and water (aqueous phase). The O/W nanoemulsion of BBH showed a
      relative bioavailability of 440.40% compared with unencapsulated BBH and was
      stable in our 6-month stability study. Further, there was a significant increase
      in intestinal permeability of BBH as assessed by Caco-2 cell monolayers and a
      significant reduction in efflux of BBH by the multidrug efflux pump P
      glycoprotein. This study confirmed that the nanoemulsion formulation could be
      used as an alternative oral formulation of BBH to improve its stability, oral
      bioavailability and permeability.

PMID- 29191059
TI  - Optimization of biologic therapy in Crohn's disease.
AB  - INTRODUCTION: Crohn's disease (CD) is a manifestation of inflammatory bowel
      disease (IBD), which can result in significant morbidity. Biologic therapy with
      anti-TNF medication has been effective in treating inflammation and reducing
      complications in CD. It is important for clinicians to have better knowledge of
      the various biologic therapies including mechanisms of action and optimization
      strategies. Areas covered: The review describes optimization of biologic therapy
      in CD including different mechanisms of loss of response, therapeutic drug
      monitoring in CD, clinical implications and management strategies which utilize
      drug monitoring, and areas of future development and research in optimization of
      biologic therapy. Expert opinion: Achieving adequate levels of the drug (antibody
      unbound) is one of the most important determinants of attaining clinical
      remission and mucosal healing. Drug level is also critical in determining if a
      patient requires combination therapy with an immunomodulator. Certain
      populations, including those with active perianal disease, may require higher
      serum levels to achieve healing or closure. Treat to target level is an algorithm
      that is not universally accepted and more data is need. Additionally, there are
      numerous assays that don't always correlate, especially regarding measuring anti
      drug antibodies.

PMID- 29191060
TI  - Endoscopic endonasal resection of a medullary cavernoma: a novel case.
AB  - Brainstem cavernomas can present very challenging operative problems. Endoscopic
      endonasal approaches to these lesions in the mesencephalon and pons have been
      described. In this article the authors present the first case of a medullary
      cavernoma resected by an endoscopic transclival approach. A 26 year-old woman
      with a 1.5 cm medullary cavernoma presented with imbalance, swallowing
      difficulty, and right hemibody weakness. She was taken to the operating room for
      endoscopic endonasal transclival resection. Her pre-existing neurologic deficits
      worsened initially after surgery, but at three-month follow-up she had made a
      full neurologic recovery.

PMID- 29191061
TI  - The identification of new ATAD2 bromodomain inhibitors: the application of
      combined ligand and structure-based virtual screening.
AB  - Ligand-based virtual screening (LBVS) and structure-based virtual screening
      (SBVS) approaches were used to identify new inhibitors for ATAD2 bromodomain. The
      LBVS approach was used to search 23,129,083 clean compounds to identify compounds
      similar to an active compound with reported pIC50 equal to 7.2. Based on LBVS
      results, 19 compounds were selected. To perform SBVS, by applying nine filters on
      23,129,083 clean compounds, 1,057,060 compounds were selected. After performing
      SBVS on these selected compounds with idock software, 16 compounds with the
      lowest binding energies were selected. More accurate molecular docking analysis
      was performed on these 35 selected compounds by using iGEMDOCK software and six
      of them with the lowest binding energies were selected as hit compounds. These
      compounds were zinc36647229, zinc77969074, zinc13637358, zinc77971540,
      zinc12991296 and zinc19374204.

PMID- 29191062
TI  - Recurrent Bell's palsy following ventriculoperitoneal shunt insertion: an unusual
      case to face.
AB  - We present the case of a 15 year old boy who developed transient lower motor
      neuron facial weakness on two separate occasions shortly after
      ventriculoperitoneal shunt insertion. Both episodes, each of which occurred on
      the ipsilateral side to shunt insertion, were transient, self-limiting and were
      managed medically with a course of oral steroids. We believe this is the first
      reported case of Bell's palsy after this type of surgery in a child. Potential
      pathophysiological mechanisms are discussed.

PMID- 29191064
TI  - The future of pharmacogenetics in Parkinson's disease treatment.

PMID- 29191063
TI  - Changes in DNA methylation induced by multi-walled carbon nanotube exposure in
      the workplace.
AB  - This study was designed to assess the epigenetic alterations in blood cells,
      induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The
      study population comprised of MWCNT-exposed workers (n=24) and unexposed controls
      (n=43) from the same workplace. We measured global DNA
      methylation/hydroxymethylation levels on the 5th cytosine residues using a
      validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method.
      Sequence-specific methylation of LINE1 retrotransposable element 1 (L1RE1)
      elements, and promoter regions of functionally important genes associated with
      epigenetic regulation [DNA methyltransferase-1 (DNMT1) and histone deacetylase 4
      (HDAC4)], DNA damage/repair and cell cycle pathways [nuclear protein, coactivator
      of histone transcription/ATM serine/threonine kinase (NPAT/ATM)], and a potential
      transforming growth factor beta (TGF-beta) repressor [SKI proto-oncogene (SKI)]
      were studied using bisulfite pyrosequencing. Analysis of global DNA methylation
      levels and hydroxymethylation did not reveal significant difference between the
      MWCNT-exposed and control groups. No significant changes in Cytosine-phosphate
      Guanine (CpG) site methylation were observed for the LINE1 (L1RE1) elements.
      Further analysis of gene-specific DNA methylation showed a significant change in
      methylation for DNMT1, ATM, SKI, and HDAC4 promoter CpGs in MWCNT-exposed
      workers. Since DNA methylation plays an important role in silencing/regulation of
      the genes, and many of these genes have been associated with occupational and
      smoking-induced diseases and cancer (risk), aberrant methylation of these genes
      might have a potential effect in MWCNT-exposed workers.

PMID- 29191065
TI  - Physiological responses of the Drosophila labellum to amino acids.
AB  - We have systematically studied the physiological responses elicited by amino
      acids from the principal taste organ of the Drosophila head. Although the
      detection and coding of sugars and bitter compounds have been examined
      extensively in this organism, little attention has been paid to the physiology of
      amino acid taste. We find that one class of sensilla, the S sensilla, yield the
      strongest responses to amino acids, although these responses were much weaker
      than the most robust responses to sugar or bitter compounds. S sensilla are
      heterogeneous in their amino acid responses and amino acids differ in the
      responses they elicit from individual sensilla. Tryptophan elicited relatively
      strong responses from S sensilla and these responses were eliminated when bitter
      sensing neurons were ablated. Although tryptophan yielded little if any response
      in a behavioral paradigm, phenylalanine elicited a relatively strong response in
      the same paradigm and had a different physiological profile, supporting the
      notion that different amino acids are differentially encoded by the repertoire of
      taste neurons.

PMID- 29191066
TI  - Intervention effect of gamma aminobutyric acid on anxiety behavior induced by
      phthalate (2-ethylhexyl ester) in rats.
AB  - BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used
      phthalate esters. The application of DEHP has caused serious environmental
      pollution and posed a threat to human health. METHODS: A total of 30 male Sprague
      Dawley rats were randomly divided into control group, DEHP group (500 mg/kg
      DEHP), low GABA (Gama-aminobutyric acid) group (500 mg/kg DEHP and 1 mg/kg GABA),
      medium GABA group (500 mg/kg DEHP and 2 mg/kg GABA) and high GABA group (500
      mg/kg DEHP and 4 mg/kg GABA). The interventions continued for 30 consecutive
      days. Open-field test and elevated plus-maze test were used to detect behavioral
      changes of rats before and after interventions. RESULTS: The levels of nitric
      oxide and nitric oxide synthase in prefrontal cortex of rats were measured using
      enzyme-linked immunosorbent assay. DEHP and GABA treatment had no significant
      effects on the body weight of rats. GABA restored food utilization rate of rats
      impaired by DEHP to the level of healthy rats. According to open-field test and
      elevated plus-maze test, GABA alleviated the effects of DEHP on rat behaviors.
      Enzyme-linked immunosorbent assay showed that GABA was effective in reducing the
      levels of nitric oxide and nitric oxide synthase in rats treated with DEHP.
      CONCLUSION: DEHP exposure induced anxiety in rats, which may be achieved through
      elevating nitric oxide and nitric oxide synthase levels in prefrontal cortex of
      rats. However, the effects caused by DEHP could be alleviated by GABA.

PMID- 29191067
TI  - Differences in pain intensity in anti- and pro-nociceptive pain profile subgroups
      in patients with knee osteoarthritis.
AB  - AIM: Facilitated temporal summation is one component of central sensitization.
      The aim of this exploratory study was to classify pro-, eu- and antinociceptive
      subgroups based on wind-up ratio cut-off scores in patients with knee
      osteoarthritis (OA). PATIENTS & METHODS:  A total of 56 patients with knee OA met
      the inclusion criteria. Temporal summation was measured and wind-up ratio was
      calculated. Reference values of 180 healthy subjects were used to define wind-up
      ratio cut-off scores. RESULTS: Twenty-seven percent of patients showed a pro
      nociceptive pain profile. Sixteen percent of patients showed an anti-nociceptive
      pain profile. A eu-nociceptive pain profile was present in 57% of patients.
      CONCLUSION: Central pain sensitization was present in approximately a third of
      knee OA patients. The results should be confirmed in larger studies.

PMID- 29191068
TI  - An exploratory cost-effectiveness analysis of systemic treatments for cutaneous T
      cell lymphoma.
AB  - PURPOSE: To conduct an exploratory cost-effectiveness analysis of systemic
      treatment options for more advanced cutaneous T-cell lymphoma (CTCL). METHODS: A
      cost-effectiveness model compared systemic bexarotene, denileukin diftitox,
      interferon-alpha, methotrexate, pralatrexate, romidepsin, vorinostat, and
      extracorporeal photopheresis (ECP) treatment of CTCL. Treatment effectiveness
      data were extracted from published studies and/or US product labeling. Overall
      response, the primary effectiveness measure, was defined as the proportion of
      patients achieving complete or partial response. Costs were based on wholesale
      acquisition cost (medications) and Medicare reimbursement rates (ECP, medication
      administration, adverse drug effect treatment). The perspective of the study was
      from that of a payer. RESULTS: Methotrexate was the lowest cost option [mean
      $436; standard deviation (SD) $284], followed by interferon-alpha (mean $32,174;
      SD $27,582), denileukin difitox (mean $40,107; SD $18,598), and ECP (mean
      $40,985; SD $45,633). Other treatments had costs greater than $50,000, ranging
      from vorinostat ($65,958; SD $40,637) to bexarotene ($239,424; SD $178,881). The
      incremental cost-effectiveness ratio per successfully treated patient was
      $396,725 (interferon) and $213,416 (ECP). Denileukin diftitox, romidepsin, and
      vorinostat were less effective and cost more than methotrexate. CONCLUSION:
      Methotrexate is the most cost-effective option for CTCL; however, its low cost is
      offset by its limited effectiveness in advanced stages of CTCL. ECP and
      interferon appear the next most cost-effective therapies.

PMID- 29191069
TI  - Information needs of survivors and families after childhood CNS tumor treatment:
      a population-based study.
AB  - BACKGROUND: This study examines information needs and satisfaction with provided
      information among childhood central nervous system (CNS) tumor survivors and
      their parents. MATERIAL AND METHODS: In a population-based sample of 697 adult
      survivors in Sweden, 518 survivors and 551 parents provided data. Information
      needs and satisfaction with information were studied using a multi-dimensional
      standardized questionnaire addressing information-related issues. RESULTS:
      Overall, 52% of the survivors and 48% of the parents reported no, or only minor,
      satisfaction with the extent of provided information, and 51% of the survivors
      expressed a need for more information than provided. The information received was
      found useful (to some extent/very much) by 53%, while 47% did not find it useful,
      or to a minor degree only. Obtaining written material was associated with greater
      satisfaction and usefulness of information. Dissatisfaction with information was
      associated with longer time since diagnosis, poorer current health status and
      female sex. The survivors experienced unmet information needs vis-a-vis late
      effects, illness education, rehabilitation and psychological services. Overall,
      parents were more dissatisfied than the survivors. CONCLUSION: These findings
      have implications for improvements in information delivery. Information in
      childhood CNS tumor care and follow-up should specifically address issues where
      insufficiency was identified, and recognize persistent and with time changing
      needs at the successive stages of long-term survivorship.

PMID- 29191070
TI  - Predictors of Mortality in Nondemented Patients With Parkinson Disease: Motor
      Symptoms Versus Nonmotor Symptoms.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to identify risk factors for
      mortality in a community-based cohort of nondemented patients with Parkinson
      disease (PD) during prospective long-term follow-up, while also comparing the
      effect of motor complications to nonmotor symptoms (NMS) on risk of mortality.
      METHODS: One hundred forty seven nondemented patients with PD (57.1% males; 70.9
      +/- 8.6 years old) were included in this 48 month follow-up, longitudinal,
      single, evaluation study. Motor and therapy-related complications were assessed
      using the Unified Parkinson's Disease Rating Scale/part-IV (UPDRS-IV). Non-Motor
      Symptoms Scale (NMSS) total score was used to assess NMS burden. Cox proportional
      hazard models were applied to identify independent predictors of mortality during
      follow-up. RESULTS: Twenty-two patients of 146 (15.1%) died (1 case without
      information). Both UPDRS-IV and NMSS total scores were higher at baseline in
      patients with PD who died (3.5 +/- 3.1 vs 2.4 +/- 2.4, P = .049 and 96.9 +/- 58.6
      vs 61.9 +/- 51.0, P = .004, respectively). Unadjusted hazard ratios (HRs)
      associated with UPDRS-IV and NMSS total scores among those who died during follow
      up were 1.171 (95% confidence interval [CI]: 1.012-1.357; P = .035) and 1.008
      (95% CI: 1.002-1.013; P = .006), respectively. Independent predictors of
      mortality during follow-up after adjusting for other covariates were UPDRS-IV
      (HR: 1.224; 95% CI: 1.002-1.494; P = .047), age (HR: 1.231; 95% CI: 1104-1.374; P
      < .0001), and comorbidity (Charlson Index; HR: 1.429; 95% CI: 1.023-1.994; P =
      .036), but not NMSS total score (HR: 1.005; 95% CI: 0.996-1.014; P = .263).
      CONCLUSIONS: Both motor complications (UPDRS-IV) and NMS (NMSS) were associated
      with mortality at 4 years, being motor complications an independent predictor of
      it.

PMID- 29191071
TI  - Allosteric activation of cytochrome P450 3A4 by efavirenz facilitates midazolam
      binding.
AB  - 1. The purpose of this study is to investigate the heteroactivation mechanism of
      CYP3A4 by efavirenz, which enhances metabolism of midazolam in vivo, in terms of
      its binding to CYP3A4 with in vitro spectroscopic methods. 2. Efavirenz exhibited
      a type II spectral change with binding to CYP3A4 indicating a possible inhibitor.
      Although dissociation constant (K d) was approximated as 520 MUM, efavirenz
      enhanced binding affinity of midazolam as a co-existing drug with an estimated iK
      d value of 5.6 uM which is comparable to a clinical concentration. 3. Efavirenz
      stimulated the formation of 1'-hydroxymidazolam, and the product formation rate
      (V max) concentration-dependently increased without changing the K m. Besides, an
      efavirenz analogue, [6-chloro-1,4-dihydro-4-(1-pentynyl)-4-(trifluoromethyl)-2H
      3,1-benzoxazin-2-one] (efavirenz impurity) slightly facilitated the binding
      affinity of midazolam in a concentration-dependent manner. These results propose
      that efavirenz affects midazolam-binding via binding to the peripheral site which
      is apart from the active site of CYP3A4. 4. A molecular dynamics simulation also
      suggested the bound-efavirenz was repositioned to effector-binding site. As a
      consequence, our spectroscopic studies clarified the heteroactivation of CYP3A4
      caused by efavirenz with a proper affinity to the peripheral site, and we
      concluded the method can be a useful tool for characterising the potential for
      drug-drug interactions.

PMID- 29191072
TI  - Population pharmacogenomics: impact on public health and drug development.

PMID- 29191073
TI  - Using an Allometric Equation to Accurately Predict the Energy Expenditure of
      Children and Adolescents With Nonalcoholic Fatty Liver Disease.
AB  - BACKGROUND: Pediatric patients with nonalcoholic fatty liver disease (NAFLD)
      require targeted nutrition therapy that relies on calculating energy needs.
      Common energy equations are inaccurate in predicting resting energy expenditure
      (REE), influencing total energy expenditure (TEE) estimates. Equations based on
      allometric scaling are simple, accurate, void of subjective activity and/or
      stress factor bias, and they estimate TEE. OBJECTIVE: To investigate the
      predictive accuracy of an allometric energy equation (AEE) in predicting TEE of
      children and adolescents with NAFLD. METHODS: Retrospective study performed in a
      single institution. The allometric equation was used to calculate AEE, and the
      results were compared with TEE calculated using indirect calorimetry data
      (measured REE) multiplied by an activity factor (AF) of 1.5 or 1.7. RESULTS:
      Fifty-six patients with a mean age of 13 years were included in this study. The
      agreement between TEE (using an AF of 1.5) and AEE was -96 kcal/d (confidence
      interval, -29 to 221). The predictive accuracy of the allometric equation was not
      different between obese and nonobese patients. CONCLUSIONS: Allometric equations
      allow for accurate estimation of TEE in children with NAFLD.

PMID- 29191074
TI  - Behavioural lateralization in domestic pigs (Sus scrofa)-variations between motor
      functions and individuals.
AB  - Motor lateralization is hypothesized to depend on the complexity of the motor
      function, but it might at the same time reflect hemispheric dominance within an
      individual across motor functions. We investigated possible motor lateralization
      patterns in four motor functions of different complexity (snout use in a
      manipulative task, foot use in two-stepping tasks and tail curling) in the
      domestic pig, a tetrapod species relevant as farm animal but also as a model in
      human neuroscience. A significant majority of our sample showed individual biases
      for manipulation with their snout and for curling their tail. Interestingly, the
      tail curling was lateralized towards the right at the population level and showed
      stronger lateralization patterns than the snout. Using a cluster analysis with
      combined tail and snout laterality, we identified groups of individuals with
      different lateralization patterns across motor functions that potentially reflect
      the individuals' hemispheric dominance. To conclude, our results suggest that
      pigs show lateralization patterns that depend on the motor function and on the
      individual. Such individual lateralization patterns might have broader
      implications for animal personality and welfare. Our study lays the
      methodological groundwork for future research on laterality in pigs.

PMID- 29191075
TI  - Flavonoids, cytotoxic, antioxidant and antibacterial activities of Evax pygmaea.
AB  - CONTEXT: Phytochemical study and biological potential of Evax pygmaea (L.) Brot.
      (Asteraceae) are reported for the first time. OBJECTIVE: To identify the
      secondary metabolites of Evax pygmaea and to determine its antioxidant,
      antibacterial and cytotoxic activities. MATERIALS AND METHODS: Dried aerial parts
      (1 kg) were macerated in 70% MeOH (5 L) during 72 h. The concentrated
      hydromethanolic extract was subjected to extractions with chloroform (3 * 300
      mL), ethyl acetate (3 * 300 mL) and n-butanol (3 * 300 mL), successively. VLC of
      combined ethyl acetate (EAEP) and n-butanol (BEP) fractions was followed by
      column purifications. Antioxidant activity was investigated using DPPH, CUPRAC,
      and metal chelating, beta-carotene/linoleic acid and ABTS assays. Agar method was
      used in the antibacterial study. Cytotoxic activity was determined by Brine
      shrimp lethality test in DMSO and ethanol, at varying concentrations (2, 1 and
      0.2%) and (1, 0.2 and 0.1%) successively. RESULTS: Quercetin (1), isorhamnetin 3
      O-beta-d-xyloside (2), isorhamnetin 3-O-beta-d-glucoside (3), quercetin 3-O-beta
      d-glucoside (4), quercetin 7-O-beta-D-glucoside (5), patuletin 3-O-beta-d
      glucoside (6) were isolated from for the first time from Evax genus. The EAEP was
      the most active in ABTS (IC50: <3.125 MUg/mL) assay whereas the BEEP exhibited
      the highest activity in the beta-carotene/linoleic acid assay (IC50: <3.125
      MUg/mL). The EAEP and BEP exhibited good antibacterial activity (MIC: 40-80
      ug/mL). The plant did not show any toxicity (LD50>80 ug/mL). DISCUSSION AND
      CONCLUSIONS: Six flavonoids were isolated for the first time from Evax pygmaea
      which exhibited good antioxidant and antibacterial activities.

PMID- 29191076
TI  - Customized surface-guided knee implant: Contact analysis and experimental test.
AB  - Contact pressure and stresses on the articulating surface of the tibial component
      of a total knee replacement are directly related to the joint contact forces and
      the contact area. These stresses can result in wear and fatigue damage of the
      ultra-high-molecular-weight polyethylene. Therefore, conducting stress analysis
      on a newly designed surface-guided knee implant is necessary to evaluate the
      design with respect to the polyethylene wear. Finite element modeling is used to
      analyze the design's performance in level walking, stair ascending and squatting.
      Two different constitutive material models have been used for the tibia component
      to evaluate the effect of material properties on the stress distribution. The
      contact pressure results of the finite element analysis are compared with the
      results of contact pressure using pressure-sensitive film tests. In both
      analyses, the average contact pressure remains below the material limits of ultra
      high-molecular-weight polyethylene insert. The peak von Mises stresses in 90
      degrees  of flexion and 120 degrees  of flexion (squatting) are 16.28 and 29.55
      MPa, respectively. All the peak stresses are less than the fatigue failure limit
      of ultra-high-molecular-weight polyethylene which is 32 MPa. The average contact
      pressure during 90 degrees  and 120 degrees  of flexion in squatting are 5.51 and
      5.46 MPa according to finite element analysis and 5.67 and 8.14 MPa according to
      pressure-sensitive film experiment. Surface-guided knee implants are aimed to
      resolve the limitations in activities of daily living after total knee
      replacement by providing close to normal kinematics. The proposed knee implant
      model provides patterns of motion much closer to the natural target, especially
      as the knee flexes to higher degrees during squatting.

PMID- 29191077
TI  - Reconstruction of mitogenomes by NGS and phylogenetic implications for leaf
      beetles.
AB  - Mitochondrial genome (mitogenome) sequences are frequently used to infer
      phylogenetic relationships of insects at different taxonomic levels. Next
      generation sequencing (NGS) techniques are revolutionizing many fields of
      biology, and allow for acquisition of insect mitogenomes for large number of
      species simultaneously. In this study, 20 full or partial mitogenomes were
      sequenced from pooled genomic DNA samples by NGS for leaf beetles
      (Chrysomelidae). Combined with published mitogenome sequences, a higher level
      phylogeny of Chrysomelidae was reconstructed under maximum likelihood and
      Bayesian inference with different models and various data treatments. The results
      revealed support for a basal position of Bruchinae within Chrysomelidae. In
      addition, two major subfamily groupings were recovered: one including seven
      subfamilies, namely Donaciinae, Criocerinae, Spilopyrinae, Cassidinae,
      Cryptocephalinae, Chlamisinae and Eumolpinae, another containing a non
      monophyletic Chrysomelinae and a monophyletic Galerucinae.

PMID- 29191078
TI  - Novel mutation in the KCNJ10 gene in three siblings with seizures, ataxia and no
      electrolyte abnormalities.
AB  - We report a consanguineous family with three affected siblings with novel
      mutation in the KCNJ10 gene. All three presented with central nervous system
      symptoms in the form of infantile focal seizures, ataxia, slurred speech with
      early developmental delay and intellectual disability in two siblings. None had
      any associated electrolyte abnormalities and no symptomatic hearing deficits were
      observed.

PMID- 29191079
TI  - Comparison of semen quality between university-based and private assisted
      reproductive technology laboratories.
AB  - OBJECTIVE: Obtaining a semen analysis (SA) is an essential step in evaluating
      infertile men. Despite using standardized procedures for analysis semen quality
      in the same individual often varies on repeated tests. The objective of this
      study was to investigate inter-laboratory variation in semen quality between
      private- and university-based assisted reproductive technology (ART)
      laboratories. MATERIALS AND METHODS: IRB approval was obtained to retrospectively
      evaluate men with a SA at both the private- and university-based ART
      laboratories. When more than one SA was available from either laboratory, the
      first at each laboratory was selected for analysis. Comparison of major semen
      parameters was performed using descriptive statistics and Bland-Altman plots,
      with differences tested using Wilcoxon-signed rank test. RESULTS: Twenty-eight
      men aged 33 +/- 5 (mean +/- SD) years were included in the study. Motility was
      higher at the private laboratories compared to the university-based laboratory
      (Median difference -12.5%, 95% confidence interval -20.3%; -5.5%). Percent normal
      morphology was higher at the university-based laboratory compared to private
      laboratories (5.0%, 3.6%; 6.9%). No significant differences were found in volume,
      concentration and total motile sperm count although the Bland-Altman plot bias
      for concentration was clinically significant (15.9 * 106/ml). CONCLUSIONS: In
      this small series, motility was significantly higher at private laboratories
      compared to a university-based laboratory but was above WHO reference limits at
      both places. Normal sperm morphology was significantly lower in semen analyses
      performed at private laboratories compared to a university-based laboratory and
      was below WHO reference limits.

PMID- 29191080
TI  - Case Studies of Community-Academic Partnerships Established Using the Give-Get
      Grid Model.
AB  - While partnerships for health delivery and improvement are frequently described
      by their structure, goals, and plans, less attention is paid to the interactive
      relationships among partners or for larger stakeholder groups' coalition
      memberships. The Give-Get Grid group process tool can be used to assess each
      stakeholders' expected benefits ("gets") and contributions ("gives") needed to
      establish and maintain long-term, mutually advantageous community-academic
      partnerships. This article describes three case study experiences using the Give
      Get Grid in real-world context to understand and generate ideas to address
      contemporary health promotion opportunities among a variety of stakeholders. The
      case studies address three distinct community health promotion opportunities:
      prevention of school-based adolescent obesity disparities, higher education
      health professions training programs in rural community-based settings, and
      methods for engaging community coalitions in state Comprehensive Cancer Control
      Programs. The case studies demonstrate the Give-Get Grid's utility in both
      planning and evaluating partnerships and documenting key elements for progress in
      health promotion initiatives built on long-term community-academic relationships.
      Steps are explained with practical lessons learned in using the Grid.

PMID- 29191082
TI  - Scaling Up and Tailoring the "Putting Public Health in Action" Training
      Curriculum.
AB  - Despite access to a growing menu of evidence-based interventions, public health
      practitioners continue to underuse them, in part because practitioners may
      require new knowledge, skills, and resources to do so. Numerous foundations,
      universities, governmental agencies, and consultants are providing trainings to
      address the gaps in practitioners' capacity. To most significantly affect
      population health, these trainings need to reach practitioners who may have
      limited access to on-site trainings. Despite the number of organizations offering
      trainings, little is known about how to scale up trainings to efficiently extend
      their reach or how to tailor trainings to the needs of different intervention.
      The Cancer Prevention and Control Research Network and its collaborating centers
      have developed a training curriculum and delivered it in both in-person and
      distance formats to a range of audiences. The purpose of this article is to
      describe the training curriculum and findings from the Network's evaluation of
      approaches used to scale up delivery of the "Putting Public Health Evidence in
      Action" curriculum and tailor content for specific evidence-based interventions.

PMID- 29191081
TI  - Improving Linkage, Retention, and Reengagement in HIV Care in 12 Metropolitan
      Areas.
AB  - The Centers for Disease Control and Prevention developed the Enhanced
      Comprehensive HIV Prevention Planning (ECHPP) project to support 12 health
      departments' improvement of their HIV prevention and care portfolios in response
      to new national guidelines. We systematically analyzed 3 years of progress
      reports to learn how grantees put into practice local intervention strategies
      intended to link people to, and keep them in, HIV care. All grantees initiated
      seven activities to support these strategies: (1) improve surveillance data
      systems, (2) revise staffing duties and infrastructures, (3) update policies and
      procedures, (4) establish or strengthen partnerships, (5) identify persons not in
      care, (6) train personnel, and (7) create ways to overcome obstacles to receiving
      care. Factors supporting ECHPP grantee successes were thorough planning,
      attention to detail, and strong collaboration among health department units, and
      between the health department and external stakeholders. Other jurisdictions may
      consider adopting similar strategies when planning and enhancing HIV linkage,
      retention, and reengagement efforts in their areas. ECHPP experiences, lessons
      learned, and best practices may be relevant when applying new public health
      policies that affect community and health care practices jurisdiction-wide.

PMID- 29191083
TI  - Downsizing in Europe: A social perspective.

PMID- 29191084
TI  - Agency Beliefs Over Time and Across Cultures: Free Will Beliefs Predict Higher
      Job Satisfaction.
AB  - In three studies, we examined the relationship between free will beliefs and job
      satisfaction over time and across cultures. Study 1 examined 252 Taiwanese real
      estate agents over a 3-months period. Study 2 examined job satisfaction for 137
      American workers on an online labor market over a 6-months period. Study 3
      extended to a large sample of 14,062 employees from 16 countries and examined
      country-level moderators. We found a consistent positive relationship between the
      belief in free will and job satisfaction. The relationship was above and beyond
      other agency constructs (Study 2), mediated by perceived autonomy (Studies 2-3),
      and stronger in countries with a higher national endorsement of the belief in
      free will (Study 3). We conclude that free-will beliefs predict outcomes over
      time and across cultures beyond other agency constructs. We call for more cross
      cultural and longitudinal studies examining free-will beliefs as predictors of
      real-life outcomes.

PMID- 29191085
TI  - Effects of eicosapentaenoic acid and docosahexaenoic acid on anxiety-like
      behavior in socially isolated rats.
AB  - The effects of fish oil for improving mental health have been reported. The
      present study was undertaken to compare the effects of eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) on anxiety-like behavior using a rat model.
      Experimental diets enriched in EPA or DHA as glycerides were prepared. Rats were
      exposed to social isolation stress and fed the experimental diet for 14 days. The
      results of behavioral tests revealed that rats fed the EPA-enriched diet
      exhibited less anxiety-like behavior than rats fed the control or DHA-enriched
      diets. Furthermore, EPA suppressed anxiety-like behavior only in socially
      isolated rats. The increase in EPA contents in the brain phospholipid fraction by
      feeding EPA-enriched diet was more significant than that of DHA by feeding DHA
      enriched diet. These results suggest that dietary EPA is more anxiolytic than DHA
      in rats exposed to social isolation stress and is effective in increasing EPA
      content in brain membranes.

PMID- 29191086
TI  - A modern purification method for volatile sesquiterpenes produced by recombinant
      Escherichia coli carrying terpene synthase genes.
AB  - Most volatile sesquiterpenes had been purified from plants using distillation and
      preparative gas chromatography, which is not applicable to many laboratories that
      do not possess a needed facility. Thus, this review focuses on a modern
      purification method for volatile sesquiterpenes using Escherichia coli cells that
      functionally express terpene synthase (Tps) genes. It was recently developed that
      recombinant E. coli cells carrying Tps genes were cultured in two-layer media (n
      octane/TB medium) without harming the cells, and the volatile hydrophobic
      compounds trapped in the n-octane were purified by two-phase partition
      (alkane/alkaline 50% MeOH), silica gel column chromatography, and reversed-phase
      preparative high-performance liquid chromatography (if necessary). Consequently,
      it was found that the volatile sesquiterpenes are easily purified, the structures
      of which can then be determined by nuclear magnetic resonance, [alpha]D and gas
      chromatography-mass spectrometry analyses. The antioxidant activities of several
      volatile sesquiterpenes are also presented in this review.

PMID- 29191087
TI  - Neuroprotective effect of formononetin in ameliorating learning and memory
      impairment in mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia among elderly
      population. Deranged beta-amyloid (Abeta) trafficking across the blood-brain
      barrier is known to be a critical element in the pathogenesis of AD. In the
      vascular endothelial cells of hippocampus, Abeta transport is mainly mediated by
      low-density lipoprotein-associated protein 1 (LRP1) and the receptor for advanced
      glycation end (RAGE) products; therefore, LRP1 and RAGE endothelial cells are
      potential therapeutic targets for AD. In this study, we explored the effects of
      Formononetin (FMN) on learning and memory improvement in APP/PS1 mice and the
      related mechanisms. We found that FMN significantly improved learning and memory
      ability by suppressing Abeta production from APP processing, RAGE-dependent
      inflammatory signaling and promoted LRP1-dependent cerebral Abeta clearance
      pathway. Moreover, FMN treatment alleviated ultrastructural changes in
      hippocampal vascular endothelial cells. In conclusion, we believe that FMN may be
      an efficacious and promising treatment for AD.

PMID- 29191088
TI  - The delaying effect of alpha-glycerophosphocholine on senescence, transthyretin
      deposition, and osteoarthritis in senescence-accelerated mouse prone 8 mice.
AB  - Administration of alpha-glycerophosphocholine (GPC), a choline compound in food,
      is expected to contribute to human health. In this study, we evaluated its effect
      on aging in senescence-accelerated mouse prone 8 (SAMP8) mice. Male SAMP8 mice
      had free access to a commercial stock diet and drinking water with or without GPC
      (0.07 mg/ml). Mice in the GPC group had significantly lower total senescence
      grading score than that of the control group at 36 weeks of age. Administration
      of GPC decreased the deposition of transthyretin (TTR), an amyloidogenic protein,
      in the brain. Aggregated TTR activated microglia and led to neuroinflammation.
      Thus, GPC would protect the brain by reducing TTR deposition and preventing
      neuroinflammation. In a histological study of knee joints, it was found that
      SAMP8 mice administered GPC showed decreased joint degeneration. These results
      suggest that GPC delays the aging process and may be a useful compound in anti
      aging functional food development.

PMID- 29191089
TI  - Purification and characterization of small and large rubber particles from Hevea
      brasiliensis.
AB  - Natural rubber (NR) is synthesized by the rubber transferase (RTase) on rubber
      particles (RPs) in latex. Due to the heterogeneity of the RPs in latex, it is
      difficult to precisely characterize the RTase activity. In this study, we
      separated the RPs of Hevea brasiliensis with different particle size
      distributions, via stepwise centrifugations. Analyses of protein compositions and
      size distributions of NR in the RPs suggest that RPs in Hevea latex can be
      categorized into two distinct subclasses, the larger RPs (termed 1kRP, 2kRP, and
      8kRP) and the smaller RPs (termed 20kRP and 50kRP). Precise enzymatic assays
      using the RPs revealed that 50kRP showed the highest RTase activity, whereas the
      larger RPs, which had been regarded to have quite low activity, also exhibited a
      comparable activity to the smaller RPs. Immunological detections of cis
      prenyltransferases in the RPs showed that the abundance of these enzymes
      correlates with the extent of RTase activity.

PMID- 29191091
TI  - Schizosaccharomyces japonicus has low levels of CoQ10 synthesis, respiration
      deficiency, and efficient ethanol production.
AB  - Coenzyme Q (CoQ) is essential for mitochondrial respiration and as a cofactor for
      sulfide quinone reductase. Schizosaccharomyces pombe produces a human-type CoQ10.
      Here, we analyzed CoQ in other fission yeast species. S. cryophilus and S.
      octosporus produce CoQ9. S. japonicus produces low levels of CoQ10, although all
      necessary genes for CoQ synthesis have been identified in its genome. We
      expressed three genes (dps1, dlp1, and ppt1) for CoQ synthesis from S. japonicus
      in the corresponding S. pombe mutants, and confirmed that they were functional.
      S. japonicus had very low levels of oxygen consumption and was essentially
      respiration defective, probably due to mitochondrial dysfunction. S. japonicus
      grows well on minimal medium during anaerobic culture, indicating that it
      acquires sufficient energy by fermentation. S. japonicus produces comparable
      levels of ethanol under both normal and elevated temperature (42  degrees C)
      conditions, at which S. pombe is not able to grow.

PMID- 29191090
TI  - Alterations in circadian and meal-induced gut peptide levels in lean and obese
      rats.
AB  - Alterations in gut hormone signaling are a likely contributing factor to the
      metabolic disturbances associated with overweight/obesity as they coordinate the
      timing of feeding behavior, absorption, and utilization of nutrients. These
      hormones are released in response to food intake, or follow a circadian or
      anticipatory pattern of secretion that is independent of nutrient stimulation.
      The aim of this study was to identify the degree to which high-fat diet-induced
      obesity would alter the daily rhythm of gut peptide plasma levels (glucagon-like
      peptide-1 [GLP-1], peptide YY [PYY], insulin or amylin [AMY]) or meal-induced
      levels in the middle of the light or dark cycle. Male Sprague-Dawley rats were
      fed a high-fat diet (OBESE) or chow (LEAN), implanted with jugular catheters, and
      blood samples were taken every 2 h throughout the light/dark cycle while freely
      feeding or after an Ensure liquid meal. We found that even when OBESE and LEAN
      animals ate the same kcals and have a similar pattern of food intake, there is a
      difference in both the levels and rhythm of plasma gut peptides. GLP-1 and PYY
      are higher during the light cycle in LEAN animals and AMY is higher in the OBESE
      group throughout the light/dark cycle. There was also a differential response of
      plasma gut signals after the Ensure meal, even though the composition and amount
      of intake of the meal were the same in both groups. These changes occur prior to
      the high-fat diet induced loss of glycemic control and may be a target for early
      intervention. Impact statement The aim of this study was to test if obesity would
      alter the daily rhythm of gut peptides or meal-induced levels in the middle of
      the light or dark cycle. We found that even when animals are eating the same
      amount (in kcal) of food that the obese animals have altered daily rhythms and
      meal-induced gut peptide levels. In particular, we are the first to show that
      obesity induces increases in peptide YY levels during the light cycle and amylin
      remains high throughout the light and dark cycle in obese animals. These changes
      occurred prior to a loss of glycemic control. Thus, the rhythm of gut peptides
      could be used as an early indicator of later and more serious metabolic
      disturbances and may be a target for early intervention.

PMID- 29191092
TI  - Plant-derived isoprenoid sweeteners: recent progress in biosynthetic gene
      discovery and perspectives on microbial production.
AB  - Increased public awareness of negative health effects associated with excess
      sugar consumption has triggered increasing interest in plant-derived natural
      sweeteners. Steviol glycosides are a group of highly sweet diterpene glycosides
      contained in the leaves of stevia (Stevia rebaudiana). Mogrosides, extracted from
      monk fruit (Siraitia grosvenorii), are a group of cucurbitane-type triterpenoid
      glycosides. Glycyrrhizin is an oleanane-type triterpenoid glycoside derived from
      the underground parts of Glycyrrhiza plants (licorice). This review focuses on
      the natural isoprenoid sweetening agents steviol glycosides, mogrosides, and
      glycyrrhizin, and describes recent progress in gene discovery and elucidation of
      the catalytic functions of their biosynthetic enzymes. Recently, remarkable
      progress has been made in engineering the production of various plant-specialized
      metabolites in microbial hosts such as Saccharomyces cerevisiae via the
      introduction of biosynthetic enzyme genes. Perspectives on the microbial
      production of plant-derived natural sweeteners are also discussed.

PMID- 29191093
TI  - Branched-chain amino acids regulate type I tropocollagen and type III
      tropocollagen syntheses via modulation of mTOR in the skin.
AB  - Branched-chain amino acids (BCAAs) exhibit many physiological functions. However,
      the potential link and mechanism between BCAA and skin function are unknown. We
      examined the effects of deletion of branched-chain alpha-keto acid dehydrogenase
      kinase (BDK), a key enzyme in BCAA catabolism, on type I and III tropocollagen
      syntheses in mice. Leucine and isoleucine levels were significantly lower in the
      skin of BDK-KO mice compared with wild-type mice. No changes in valine
      concentrations were observed. The levels of type I and III tropocollagen proteins
      and mRNAs (COL1A1 and COL3A1) were significantly lower in the skin of BDK-KO mice
      compared with wild-type mice. The phosphorylation of p70 S6 kinase, which
      indicates mammalian target of rapamycin (mTOR) activation, was reduced in the
      skin of BDK-KO mice compared with wild-type mice. These findings suggest that
      deficiencies of leucine and isoleucine reduce type I and III tropocollagen
      syntheses in skin by suppressing the action of mTOR.

PMID- 29191094
TI  - Potential of predictive computer models for preoperative patient selection to
      enhance overall quality-adjusted life years gained at 2-year follow-up: a
      simulation in 234 patients with adult spinal deformity.
AB  - OBJECTIVE Patients with adult spinal deformity (ASD) experience significant
      quality of life improvements after surgery. Treatment, however, is expensive and
      complication rates are high. Predictive analytics has the potential to use many
      variables to make accurate predictions in large data sets. A validated minimum
      clinically important difference (MCID) model has the potential to assist in
      patient selection, thereby improving outcomes and, potentially, cost
      effectiveness. METHODS The present study was a retrospective analysis of a
      multiinstitutional database of patients with ASD. Inclusion criteria were as
      follows: age >= 18 years, radiographic evidence of ASD, 2-year follow-up, and
      preoperative Oswestry Disability Index (ODI) > 15. Forty-six variables were used
      for model training: demographic data, radiographic parameters, surgical
      variables, and results on the health-related quality of life questionnaire.
      Patients were grouped as reaching a 2-year ODI MCID (+MCID) or not (-MCID). An
      ensemble of 5 different bootstrapped decision trees was constructed using the
      C5.0 algorithm. Internal validation was performed via 70:30 data split for
      training/testing. Model accuracy and area under the curve (AUC) were calculated.
      The mean quality-adjusted life years (QALYs) and QALYs gained at 2 years were
      calculated and discounted at 3.5% per year. The QALYs were compared between
      patients in the +MCID and -MCID groups. RESULTS A total of 234 patients met
      inclusion criteria (+MCID 129, -MCID 105). Sixty-nine patients (29.5%) were
      included for model testing. Predicted versus actual results were 50 versus 40 for
      +MCID and 19 versus 29 for -MCID (i.e., 10 patients were misclassified). Model
      accuracy was 85.5%, with 0.96 AUC. Predicted results showed that patients in the
      +MCID group had significantly greater 2-year mean QALYs (p = 0.0057) and QALYs
      gained (p = 0.0002). CONCLUSIONS A successful model with 85.5% accuracy and 0.96
      AUC was constructed to predict which patients would reach ODI MCID. The patients
      in the +MCID group had significantly higher mean 2-year QALYs and QALYs gained.
      This study provides proof of concept for using predictive modeling techniques to
      optimize patient selection in complex spine surgery.

PMID- 29191095
TI  - Male sex may not be associated with worse outcomes in primary all-posterior adult
      spinal deformity surgery: a multicenter analysis.
AB  - OBJECTIVE Adolescent spine deformity studies have shown that male patients
      require longer surgery and have greater estimated blood loss (EBL) and
      complications compared with female patients. No studies exist to support this
      relationship in adult spinal deformity (ASD). The purpose of this study was to
      investigate associations between sex and complications, deformity correction, and
      health-related quality of life (HRQOL) in patients with ASD. It was hypothesized
      that male ASD patients would have greater EBL, longer surgery, and more
      complications than female ASD patients. METHODS A multicenter ASD cohort was
      retrospectively queried for patients who underwent primary posterior-only
      instrumented fusions with a minimum of 5 levels fused. The minimum follow-up was
      2 years. Primary outcomes were EBL, operative time, intra-, peri-, and
      postoperative complications, radiographic correction, and HRQOL outcomes
      (Oswestry Disability Index, SF-36, and Scoliosis Research Society-22r
      Questionnaire). Poisson multivariate regression was used to control for age,
      comorbidities, and levels fused. RESULTS Ninety male and 319 female patients met
      the inclusion criteria. Male patients had significantly greater mean EBL (2373 ml
      vs 1829 ml, p = 0.01). The mean operative time, transfusion requirements, and
      final radiographic measurements did not differ between sexes. Similarly, changes
      in HRQOL showed no significant differences. Finally, there were no sex
      differences in the incidence of complications (total, major, or minor) at any
      time point after controlling for age, body mass index, comorbidities, and levels
      fused. CONCLUSIONS Despite higher EBL, male ASD patients did not experience more
      complications or require less deformity correction at the 2-year follow-up. HRQOL
      scores similarly showed no sex differences. These findings differ from adolescent
      deformity studies, and surgeons can counsel patients that sex is unlikely to
      influence the outcomes and complication rates of primary all-posterior ASD
      surgery.

PMID- 29191096
TI  - Lumbar computed tomography scans are not appropriate surrogates for bone mineral
      density scans in primary adult spinal deformity.
AB  - OBJECTIVE The authors examined the correlation between lumbar spine CT Hounsfield
      unit (HU) measurements and bone mineral density measurements in an adult spinal
      deformity (ASD) population. METHODS Patients with ASD were identified in the
      records of a single institution. Lumbar CT scans were reviewed, and the mean HU
      measurements from L1-4 were recorded. Bone mineral density (BMD) was assessed
      using femoral neck and lumbar spine dual-energy x-ray absorptiometry (DEXA). The
      number of patients who met criteria for osteoporosis was determined for each
      imaging modality. RESULTS Forty-eight patients underwent both preoperative DEXA
      and CT scanning. Forty-three patients were female and 5 were male. Forty-seven
      patients were Caucasian and one was African American. The mean age of the
      patients was 62.1 years. Femoral neck DEXA was more likely to identify osteopenia
      (n = 26) than lumbar spine DEXA (n = 8) or lumbar CT HU measurements (n = 6) (p <
      0.001). There was a low-moderate correlation between lumbar spine CT and lumbar
      spine DEXA (r = 0.463, p < 0.001), and there was poor correlation between lumbar
      spine CT and femoral neck DEXA (r = 0.303, p = 0.036). CONCLUSIONS Despite the
      opportunistic utility of lumbar spine CT HU measurements in identifying
      osteoporosis in patients undergoing single-level fusion, these measurements were
      not useful in this cohort of ASD patients. The correlation between femoral neck
      DEXA and HU measurements was poor. DEXA assessment of BMD in ASD patients is
      essential to optimize the care of these complicated cases.

PMID- 29191097
TI  - Introduction. Adult spinal deformity.

PMID- 29191098
TI  - Complication rates associated with open versus percutaneous pedicle screw
      instrumentation among patients undergoing minimally invasive interbody fusion for
      adult spinal deformity.
AB  - OBJECTIVE High-quality studies that compare outcomes of open and minimally
      invasively placed pedicle screws for adult spinal deformity are needed.
      Therefore, the authors compared differences in complications from a
      circumferential minimally invasive spine (MIS) surgery and those from a hybrid
      surgery. METHODS A retrospective review of a multicenter database of patients
      with spinal deformity who were treated with an MIS surgery was performed.
      Database inclusion criteria included an age of >= 18 years and at least 1 of the
      following: a coronal Cobb angle of > 20 degrees , a sagittal vertical axis of > 5
      cm, a pelvic incidence-lumbar lordosis angle of > 10 degrees , and/or a pelvic
      tilt of > 20 degrees . Patients were propensity matched according to the levels
      instrumented. RESULTS In this database, a complete data set was available for 165
      patients, and after those who underwent 3-column osteotomy were excluded, 137
      patients were available for analysis; 76 patients remained after propensity
      matching (MIS surgery group 38 patients, hybrid surgery group 38 patients). The
      authors found no difference in demographics, number of levels instrumented, or
      preoperative and postoperative radiographic results. At least 1 complication was
      suffered by 55.3% of patients in the hybrid surgery group and 44.7% of those in
      the MIS surgery group (p = 0.359). Patients in the MIS surgery group had
      significantly fewer neurological, operative, and minor complications than those
      in the hybrid surgery group. The reoperation rates in both groups were similar.
      The most common complication category for the MIS surgery group was radiographic
      and for the hybrid surgery group was neurological. Patients in both groups
      experienced postoperative improvement in their Oswestry Disability Index and
      visual analog scale (VAS) back and leg pain scores (all p < 0.05); however, MIS
      surgery provided a greater reduction in leg pain according to VAS scores.
      CONCLUSIONS Overall complication rates in the MIS and hybrid surgery groups were
      similar. MIS surgery resulted in significantly fewer neurological, operative, and
      minor complications. Reoperation rates in the 2 groups were similar, and despite
      complications, the patients reported significant improvement in their pain and
      function.

PMID- 29191099
TI  - An assessment of frailty as a tool for risk stratification in adult spinal
      deformity surgery.
AB  - OBJECTIVE The goal of this study was to analyze the value of an adult spinal
      deformity frailty index (ASD-FI) in preoperative risk stratification.
      Preoperative risk assessment is imperative before procedures known to have high
      complication rates, such as ASD surgery. Frailty has been associated with risk of
      complications in trauma surgery, and preoperative frailty assessments could
      improve the accuracy of risk stratification by providing a comprehensive analysis
      of patient factors that contribute to an increased risk of complications. METHODS
      Using 40 variables, the authors calculated frailty scores with a validated method
      for 417 patients (enrolled between 2010 and 2014) with a minimum 2-year follow-up
      in an ASD database. On the basis of these scores, the authors categorized
      patients as not frail (NF) (< 0.3 points), frail (0.3-0.5 points), or severely
      frail (SF) (> 0.5 points). The correlation between frailty category and incidence
      of complications was analyzed. RESULTS The overall mean ASD-FI score was 0.33
      (range 0.0-0.8). Compared with NF patients (n = 183), frail patients (n = 158)
      and SF patients (n = 109) had longer mean hospital stays (1.2 and 1.6 times
      longer, respectively; p < 0.001). The adjusted odds of experiencing a major
      intraoperative or postoperative complication were higher for frail patients (OR
      2.8) and SF patients ( 4.1) compared with NF patients (p < 0.01). For frail and
      SF patients, respectively, the adjusted odds of developing proximal junctional
      kyphosis (OR 2.8 and 3.1) were higher than those for NF patients. The SF patients
      had higher odds of developing pseudarthrosis (OR 13.0), deep wound infection (OR
      8.0), and wound dehiscence (OR 13.4) than NF patients (p < 0.05), and they had
      2.1 times greater odds of reoperation (p < 0.05). CONCLUSIONS Greater patient
      frailty, as measured by the ASD-FI, was associated with worse outcome in many
      common quality and value metrics, including greater risk of major complications,
      proximal junctional kyphosis, pseudarthrosis, deep wound infection, wound
      dehiscence, reoperation, and longer hospital stay.

PMID- 29191100
TI  - Preliminary results of anterior lumbar interbody fusion, anterior column
      realignment for the treatment of sagittal malalignment.
AB  - OBJECTIVE Sagittal malalignment decreases patients' quality of life and may
      require surgical correction to achieve realignment goals. High-risk posterior
      based osteotomy techniques are the current standard treatment for addressing
      sagittal malalignment. More recently, anterior lumbar interbody fusion, anterior
      column realignment (ALIF ACR) has been introduced as an alternative for
      correction of sagittal deformity. The objective of this paper was to report
      clinical and radiographic results for patients treated using the ALIF-ACR
      technique. METHODS A retrospective study of 39 patients treated with ALIF ACR was
      performed. Patient demographics, operative details, radiographic parameters,
      neurological assessments, outcome measures, and preoperative, postoperative, and
      mean 1-year follow-up complications were studied. RESULTS The patient population
      comprised 39 patients (27 females and 12 males) with a mean follow-up of 13.3 +/-
      4.7 months, mean age of 66.1 +/- 11.6 years, and mean body mass index of 27.3 +/-
      6.2 kg/m2. The mean number of ALIF levels treated was 1.5 +/- 0.5. Thirty-three
      (84.6%) of 39 patients underwent posterior spinal fixation and 33 (84.6%) of 39
      underwent posterior column osteotomy, of which 20 (60.6%) of 33 procedures were
      performed at the level of the ALIF ACR. Pelvic tilt, sacral slope, and pelvic
      incidence were not statistically significantly different between the preoperative
      and postoperative periods and between the preoperative and 1-year follow-up
      periods (except for PT between the preoperative and 1-year follow-up, p = 0.018).
      Sagittal vertical axis, T-1 spinopelvic inclination, lumbar lordosis, pelvic
      incidence-lumbar lordosis mismatch, intradiscal angle, and motion segment angle
      all improved from the preoperative to postoperative period and the preoperative
      to 1-year follow-up (p < 0.05). The changes in motion segment angle and
      intradiscal angle achieved in the ALIF-ACR group without osteotomy compared with
      the ALIF-ACR group with osteotomy at the level of ACR were not statistically
      significant. Total visual analog score, Oswestry Disability Index, and Scoliosis
      Research Society-22 scores all improved from preoperative to postoperative and
      preoperative to 1-year follow-up. Fourteen patients (35.9%) experienced 26
      complications (15 major and 11 minor). Eleven patients required reoperation. The
      most common complication was proximal junctional kyphosis (6/26 complications,
      23%) followed by vertebral body/endplate fracture (3/26, 12%). CONCLUSIONS This
      study showed satisfactory radiographic and clinical outcomes at the 1-year follow
      up. Proximal junctional kyphosis was the most common complication followed by
      fracture, complications that are commonly associated with sagittal realignment
      surgery and may not be mitigated by the anterior approach.

PMID- 29191101
TI  - Despite worse baseline status depressed patients achieved outcomes similar to
      those in nondepressed patients after surgery for cervical deformity.
AB  - OBJECTIVE Depression and anxiety have been demonstrated to have negative impacts
      on outcomes after spine surgery. In patients with cervical deformity (CD), the
      psychological and physiological burdens of the disease may overlap without clear
      boundaries. While surgery has a proven record of bringing about significant pain
      relief and decreased disability, the impact of depression and anxiety on recovery
      from cervical deformity corrective surgery has not been previously reported on in
      the literature. The purpose of the present study was to determine the effect of
      depression and anxiety on patients' recovery from and improvement after CD
      surgery. METHODS The authors conducted a retrospective review of a prospective,
      multicenter CD database. Patients with a history of clinical depression, in
      addition to those with current self-reported anxiety or depression, were defined
      as depressed (D group). The D group was compared with nondepressed patients (ND
      group) with a similar baseline deformity determined by propensity score matching
      of the cervical sagittal vertical axis (cSVA). Baseline demographic, comorbidity,
      clinical, and radiographic data were compared among patients using t-tests.
      Improvement of symptoms was recorded at 3 months, 6 months, and 1 year
      postoperatively. All health-related quality of life (HRQOL) scores collected at
      these follow-up time points were compared using t-tests. RESULTS Sixty-six
      patients were matched for baseline radiographic parameters: 33 with a history of
      depression and/or current depression, and 33 without. Depressed patients had
      similar age, sex, race, and radiographic alignment: cSVA, T-1 slope minus C2-7
      lordosis, SVA, and T-1 pelvic angle (p > 0.05). Compared with nondepressed
      individuals, depressed patients had a higher incidence of osteoporosis (21.2% vs
      3.2%, p = 0.028), rheumatoid arthritis (18.2% vs 3.2%, p = 0.012), and connective
      tissue disorders (18.2% vs 3.2%, p = 0.012). At baseline, the D group had greater
      neck pain (7.9 of 10 vs 6.6 on a Numeric Rating Scale [NRS], p = 0.015), lower
      mean EQ-5D scores (68.9 vs 74.7, p < 0.001), but similar Neck Disability Index
      (NDI) scores (57.5 vs 49.9, p = 0.063) and myelopathy scores (13.4 vs 13.9, p =
      0.546). Surgeries performed in either group were similar in terms of number of
      levels fused, osteotomies performed, and correction achieved (baseline to 3-month
      measurements) (p < 0.05). At 3 months, EQ-5D scores remained lower in the D group
      (74.0 vs 78.2, p = 0.044), and NDI scores were similar (48.5 vs 39.0, p = 0.053).
      However, neck pain improved in the D group (NRS score of 5.0 vs 4.3, p = 0.331),
      and modified Japanese Orthopaedic Association (mJOA) scores remained similar
      (14.2 vs 15.0, p = 0.211). At 6 months and 1 year, all HRQOL scores were similar
      between the 2 cohorts. One-year measurements were as follows: NDI 39.7 vs 40.7 (p
      = 0.878), NRS neck pain score of 4.1 vs 5.0 (p = 0.326), EQ-5D score of 77.1 vs
      78.2 (p = 0.646), and mJOA score of 14.0 vs 14.2 (p = 0.835). Anxiety/depression
      levels reported on the EQ-5D scale were significantly higher in the depressed
      cohort at baseline, 3 months, and 6 months (all p < 0.05), but were similar
      between groups at 1 year postoperatively (1.72 vs 1.53, p = 0.416). CONCLUSIONS
      Clinical depression was observed in many of the study patients with CD. After
      matching for baseline deformity, depression symptomology resulted in worse
      baseline EQ-5D and pain scores. Despite these baseline differences, both cohorts
      achieved similar results in all HRQOL assessments 6 months and 1 year
      postoperatively, demonstrating no clinical impact of depression on recovery up
      until 1 year after CD surgery. Thus, a history of depression does not appear to
      have an impact on recovery from CD surgery.

PMID- 29191102
TI  - Impact of case type, length of stay, institution type, and comorbidities on
      Medicare diagnosis-related group reimbursement for adult spinal deformity
      surgery.
AB  - OBJECTIVE The aim of this study was to educate medical professionals about
      potential financial impacts of improper diagnosis-related group (DRG) coding in
      adult spinal deformity (ASD) surgery. METHODS Medicare's Inpatient Prospective
      Payment System PC Pricer database was used to collect 2015 reimbursement data for
      ASD procedures from 12 hospitals. Case type, hospital type/location, number of
      operative levels, proper coding, length of stay, and complications/comorbidities
      (CCs) were analyzed for effects on reimbursement. DRGs were used to categorize
      cases into 3 types: 1) anterior or posterior only fusion, 2) anterior fusion with
      posterior percutaneous fixation with no dorsal fusion, and 3) combined anterior
      and posterior fixation and fusion. RESULTS Pooling institutions, cases were
      reimbursed the same for single-level and multilevel ASD surgery. Longer stay,
      from 3 to 8 days, resulted in an additional $1400 per stay. Posterior fusion was
      an additional $6588, while CCs increased reimbursement by approximately $13,000.
      Academic institutions received higher reimbursement than private institutions,
      i.e., approximately $14,000 (Case Types 1 and 2) and approximately $16,000 (Case
      Type 3). Urban institutions received higher reimbursement than suburban
      institutions, i.e., approximately $3000 (Case Types 1 and 2) and approximately
      $3500 (Case Type 3). Longer stay, from 3 to 8 days, increased reimbursement
      between $208 and $494 for private institutions and between $1397 and $1879 for
      academic institutions per stay. CONCLUSIONS Reimbursement is based on many
      factors not controlled by surgeons or hospitals, but proper DRG coding can
      significantly impact the financial health of hospitals and availability of
      quality patient care.

PMID- 29191103
TI  - Relative lumbar lordosis and lordosis distribution index: individualized pelvic
      incidence-based proportional parameters that quantify lumbar lordosis more
      precisely than the concept of pelvic incidence minus lumbar lordosis.
AB  - OBJECTIVE The subtraction of lumbar lordosis (LL) from the pelvic incidence (PI)
      offers an estimate of the LL required for a given PI value. Relative LL (RLL) and
      the lordosis distribution index (LDI) are PI-based individualized measures. RLL
      quantifies the magnitude of lordosis relative to the ideal lordosis as defined by
      the magnitude of PI. LDI defines the magnitude of lower arc lordosis in
      proportion to total lordosis. The aim of this study was to compare RLL and PI -
      LL for their ability to predict postoperative complications and their
      correlations with health-related quality of life (HRQOL) scores. METHODS
      Inclusion criteria were >= 4 levels of fusion and >= 2 years of follow-up.
      Mechanical complications were proximal junctional kyphosis/proximal junctional
      failure, distal junctional kyphosis/distal junctional failure, rod breakage, and
      implant-related complications. Correlations between PI - LL, RLL, PI, and HRQOL
      were analyzed using the Pearson correlation coefficient. Mechanical complication
      rates in PI - LL, RLL, LDI, RLL, and LDI interpreted together, and RLL subgroups
      for each PI - LL category were compared using chi-square tests and the exact
      test. Predictive models for mechanical complications with RLL and PI - LL were
      analyzed using binomial logistic regressions. RESULTS Two hundred twenty-two
      patients (168 women, 54 men) were included. The mean age was 52.2 +/- 19.3 years
      (range 18-84 years). The mean follow-up was 28.8 +/- 8.2 months (range 24-62
      months). There was a significant correlation between PI - LL and PI (r = 0.441, p
      < 0.001), threatening the use of PI - LL to quantify spinopelvic mismatch for
      different PI values. RLL was not correlated with PI (r = -0.093, p > 0.05);
      therefore, it was able to quantify divergence from ideal lordosis for all PI
      values. Compared with PI - LL, RLL had stronger correlations with HRQOL scores (p
      < 0.05). Discrimination performance was better for the model with RLL than for PI
      - LL. The agreement between RLL and PI - LL was high (kappa = 0.943, p < 0.001),
      moderate (kappa = 0.455, p < 0.001), and poor (kappa = -0.154, p = 0.343),
      respectively, for large, average, and small PI sizes. When analyzed by RLL, each
      PI - LL category was further divided into distinct groups of patients who had
      different mechanical complication rates (p < 0.001). CONCLUSIONS Using the
      formula of PI - LL may be insufficient to quantify normolordosis for the whole
      spectrum of PI values when applied as an absolute numeric value in conjunction
      with previously reported population-based average thresholds of 10 degrees  and
      20 degrees . Schwab PI - LL groups were found to constitute an inhomogeneous
      group of patients. RLL offers an individualized quantification of LL for all PI
      sizes. Compared with PI - LL, RLL showed a greater association with both
      mechanical complications and HRQOL. The use of RLL and LDI together, instead of
      PI - LL, for surgical planning may result in lower mechanical complication rates
      and better long-term HRQOL.

PMID- 29191104
TI  - Does prior spine surgery or instrumentation affect surgical outcomes following 3
      column osteotomy for correction of thoracolumbar deformities?
AB  - OBJECTIVE Adult spinal deformity (ASD) develops in the setting of asymmetrical
      arthritic degeneration, and can also be due to iatrogenic causes, such as prior
      surgery. Many patients who present with ASD have undergone prior spine surgery
      with instrumentation. Unfortunately, contemporary studies that evaluate the
      effect of prior surgery or instrumentation on perioperative outcomes, readmission
      rates, and need for reoperation are lacking. METHODS All ASD patients who
      underwent a 3-column osteotomy performed by the senior author at the authors'
      institution for correction of thoracolumbar spinal deformity between 2006 and
      2016 were identified. The authors compared surgical outcomes between primary
      (first-time) and revision cases. Further subgroup analysis was conducted to
      investigate the effect of the number of prior surgeries (0, 1, 2, 3, 4, and 5 or
      more) and the presence of spinal instrumentation on outcomes. Multivariate
      analysis was used to adjust for relevant and significant confounders. RESULTS A
      total of 300 patients were included; 38.3% of patients were male. The overall
      perioperative complication rate was 24.7%, and the mean length of hospitalization
      was 8.2 days. The 90-day readmission rate was 9.0%, and the overall follow-up
      reoperation rate was 26.7%. There were no significant differences in complication
      rates (26.6% vs 24.0%, p = 0.645), length of hospitalization (8.7 vs 7.9 days, p
      = 0.229), readmission rates (11.4% vs 8.1%, p = 0.387), or reoperation rates
      (26.6% vs 26.7%, p = 0.984) between primary and revision cases. There was no
      significant difference in wound complications (infections/dehiscence) requiring
      reoperation (5.1% vs 6.3%, p = 0.683). Subgroup analysis conducted to evaluate
      the effect of the number of prior spinal surgeries or the presence of spinal
      instrumentation did not reveal significant differences for the aforementioned
      surgical outcomes. In adjusted multivariate analysis, there were no significant
      associations between history of prior surgery (number of prior surgeries and
      prior instrumentation) and all of the surgical outcomes of interest. CONCLUSIONS
      The findings from this study suggest that patients who have undergone prior spine
      surgery with or without instrumentation are not at increased risk for
      perioperative complications, need for readmission, or reoperation following 3
      column osteotomy of the thoracolumbar spine.

PMID- 29191105
TI  - Curcumin and its derivatives inhibit 2,3,7,8,-tetrachloro-dibenzo-p-dioxin
      induced expression of drug metabolizing enzymes through aryl hydrocarbon receptor
      mediated pathway.
AB  - Certain dioxins, including 2,3,7,8,-tetrachloro-dibenzo-p-dioxin (TCDD), are
      exogenous ligands for an aryl hydrocarbon receptor (AhR) and induces various drug
      metabolizing enzymes. In this study, we examined the effect of curcumin on
      expression of drug-metabolizing enzymes through the AhR and NF-E2 related factor
      2 (Nrf2) pathways. Curcumin dose-dependently inhibited TCDD-induced expression of
      phase I enzyme cytochrome P450 1A1 (CYP1A1) and phase II enzymes NAD(P)H:quinone
      oxidoreductase-1 (NQO1) and heme oxygenase 1 (HO-1) but not tert-butyl
      hydroquinone-induced NQO1 and HO-1, suggesting that curcumin inhibited only AhR
      pathway, but not Nrf2 one directly. Furthermore, we used 14 curcumin derivatives
      and obtained the correlation between hydrophobicity of the compounds and
      suppressive effect against AhR transformation. Results from the quantitative
      structure active correlative analysis indicated that methoxy groups and beta
      diketone structure possessing keto-enol tautomerism in curcumin were necessary to
      inhibit AhR transformation, and the addition of methyl and methoxy group(s) to
      the curcumin increased the inhibition effect.

PMID- 29191106
TI  - Suppression of phenotype of Escherichia coli mutant defective in farnesyl
      diphosphate synthase by overexpression of gene for octaprenyl diphosphate
      synthase.
AB  - We investigated suppression of the slow growth of an Escherichia coli ispA null
      mutant lacking farnesyl diphosphate (FPP) synthase (i.e. IspA) by plasmids
      carrying prenyl diphosphate synthase genes. The growth rates of ispA mutant
      transformants harboring a medium-copy number plasmid that carries ispA or ispB
      were almost the same as that of the wild-type strain. Although the level of FPP
      in the transformant with the ispA plasmid was almost the same as that in the wild
      type strain, the level in the transformant with the ispB plasmid was as low as
      that in the ispA mutant. Purified octaprenyl diphosphate synthase (IspB) could
      condense isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP) to
      form octaprenyl diphosphate and nonaprenyl diphosphate. It is possible that
      suppression of the slow growth of the ispA mutant by ispB was due to condensation
      of IPP not only with FPP but also with DMAPP by octaprenyl diphosphate synthase.

PMID- 29191107
TI  - Not All Skepticism Is Equal: Exploring the Ideological Antecedents of Science
      Acceptance and Rejection.
AB  - Many topics that scientists investigate speak to people's ideological worldviews.
      We report three studies-including an analysis of large-scale survey data-in which
      we systematically investigate the ideological antecedents of general faith in
      science and willingness to support science, as well as of science skepticism of
      climate change, vaccination, and genetic modification (GM). The main predictors
      are religiosity and political orientation, morality, and science understanding.
      Overall, science understanding is associated with vaccine and GM food acceptance,
      but not climate change acceptance. Importantly, different ideological predictors
      are related to the acceptance of different scientific findings. Political
      conservatism best predicts climate change skepticism. Religiosity, alongside
      moral purity concerns, best predicts vaccination skepticism. GM food skepticism
      is not fueled by religious or political ideology. Finally, religious
      conservatives consistently display a low faith in science and an unwillingness to
      support science. Thus, science acceptance and rejection have different
      ideological roots, depending on the topic of investigation.

PMID- 29191108
TI  - A Screening Tool Using Five Risk Factors Was Developed for Fall-Risk Prediction
      in Chinese Community-Dwelling Elderly Individuals.
AB  - The objective of this study was to determine falls risk profiles to derive a
      falls risk prediction score and establish a simple and practical clinical
      screening tool for Chinese community-dwelling elderly individuals. This was a
      prospective cohort study (n = 619) among adults aged 60 years and older. Falls
      were ascertained at a 1-year follow-up appointment. Sociodemographic information,
      medical history, and physical performance data were collected. The mean age was
      67.4 years; 57.7% were women. Female sex (odds ratios [ORs] 1.82; 95% confidence
      interval [95% CI] 1.17-2.82), diabetes (OR 2.13; 95% CI 1.13-3.98), a Timed Up
      and Go Test (TUGT) >=10.49 seconds (OR 1.51; 95% CI 1.23-1.94), a history of
      falls (OR 3.15; 95% CI 1.72-5.79), and depression (Geriatric Depression Scale
      [GDS] >=11, OR 2.51; 95% CI 1.36-4.63) were the strongest predictors. These
      predictors were used to establish a risk score. The area under the curve of the
      score was 0.748. From a clinical point of view, the most appropriate cutoff value
      was 7 (97.5% specificity, 70.7% positive predictive value, and 83.6% negative
      predictive value). For this cutoff, the fraction correctly classified was 82.5%.
      A cutoff score of 7 derived from a risk assessment tool using four risk factors
      (gender, falls history, diabetes, and depression) and the TUGT may be used in
      Chinese community-dwelling elderly individuals as an initial step to screen those
      at low risk for falls.

PMID- 29191109
TI  - Utilization of an intermediate of the methylerythritol phosphate pathway, (E)-4
      hydroxy-3-methylbut-2-en-1-yl diphosphate, as the prenyl donor substrate for
      various prenyltransferases.
AB  - (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) is an intermediate of the
      methylerythritol phosphate pathway. Utilization of HMBPP by lycopene elongase
      from Corynebacterium glutamicum, which is a UbiA-family prenyltransferase
      responsible for C50 carotenoid biosynthesis, was investigated using an
      Escherichia coli strain that contained the exogenous mevalonate pathway as well
      as the carotenoid biosynthetic pathway. Inhibition of the endogenous
      methylerythritol phosphate pathway resulted in loss of the production of C50
      carotenoid flavuxanthin, while C40 lycopene formation was retained.
      Overexpression of E. coli ispH gene, which encodes HMBPP reductase, also
      decreased the production of flavuxanthin in E. coli cells. These results indicate
      the preference of lycopene elongase for HMBPP instead of the previously proposed
      substrate, dimethylallyl diphosphate. Furthermore, several (all-E)-prenyl
      diphosphate synthases, which are classified in a distinct family of
      prenyltransferase, were demonstrated to accept HMBPP, which implies that the
      compound is more widely used as a prenyl donor substrate than was previously
      expected.

PMID- 29191110
TI  - Decennial trends and inequalities in healthy life expectancy: The HUNT Study,
      Norway.
AB  - AIMS: Norway is experiencing a rising life expectancy combined with an increasing
      dependency ratio - the ratio of those outside over those within the working
      force. To provide data relevant for future health policy we wanted to study
      trends in total and healthy life expectancy in a Norwegian population over three
      decades (1980s, 1990s and 2000s), both overall and across gender and educational
      groups. METHODS: Data were obtained from the HUNT Study, and the Norwegian
      Educational Database. We calculated total life expectancy and used the Sullivan
      method to calculate healthy life expectancies based on self-rated health and self
      reported longstanding limiting illness. The change in health expectancies was
      decomposed into mortality and disability effects. RESULTS: During three
      consecutive decades we found an increase in life expectancy for 30-year-olds (~7
      years) and expected lifetime in self-rated good health (~6 years), but time
      without longstanding limiting illness increased less (1.5 years). Women could
      expect to live longer than men, but the extra life years for females were spent
      in poor self-rated health and with longstanding limiting illness. Differences in
      total life expectancy between educational groups decreased, whereas differences
      in expected lifetime in self-rated good health and lifetime without longstanding
      limiting illness increased. CONCLUSIONS: The increase in total life expectancy
      was accompanied by an increasing number of years spent in good self-rated health
      but more years with longstanding limiting illness. This suggests increasing
      health care needs for people with chronic diseases, given an increasing number of
      elderly. Socioeconomic health inequalities remain a challenge for increasing
      pensioning age.

PMID- 29191112
TI  - Attitude Accessibility as a Function of Emotionality.
AB  - Despite the centrality of both attitude accessibility and attitude basis to the
      last 30 years of theoretical and empirical work concerning attitudes, little work
      has systematically investigated their relation. The research that does exist
      provides conflicting results and is not at all conclusive given the methodology
      that has been used. The current research uses recent advances in statistical
      modeling and attitude measurement to provide the most systematic examination of
      the relation between attitude accessibility and basis to date. Specifically, we
      use mixed-effects modeling which accounts for variation across individuals and
      attitude objects in conjunction with the Evaluative Lexicon (EL)-a linguistic
      approach that allows for the simultaneous measurement of an attitude's valence,
      extremity, and emotionality. We demonstrate across four studies, over 10,000
      attitudes, and nearly 50 attitude objects that attitudes based on emotion tend to
      be more accessible in memory, particularly if the attitude is positive.

PMID- 29191111
TI  - The doing and undoing of male household decision-making and economic authority in
      Rwanda and its implications for gender transformative programming.
AB  - This paper explores two key norms that underpin intimate partner violence in
      Rwanda: men's roles as economic providers and decision-making authorities in the
      household. It describes the political, legal and socio-economic factors affecting
      these norms and how they create opportunities and barriers to 'undoing'
      restrictive gender norms. Findings are drawn from an evaluation of Inadshyikirwa,
      an intimate partner violence prevention programme operating in Rwanda. Across
      three intervention sectors, 24 focus groups were conducted with unmarried and
      married men and women residing in intervention communities. Thirty interviews
      with couples and nine interviews with opinion leaders were conducted before they
      completed programme training designed to shift gender norms underlying intimate
      partner violence. The data indicate a strong awareness of and accountability to
      Rwandan laws and policies supporting women's economic empowerment and decision
      making, alongside persisting traditional notions of men as household heads and
      primary breadwinners. Transgression of these norms could be accommodated in some
      circumstances, especially those involving economic necessity. The data also
      identified increasing recognition of the value of a more equitable partnership
      model. Findings highlight the importance of carefully assessing cracks in the
      existing gender order that can be exploited to support gender equality and non
      violence.

PMID- 29191113
TI  - Characterization of cis-4-hydroxy-D-proline dehydrogenase from Sinorhizobium
      meliloti.
AB  - The hypO gene from Sinorhizobium meliloti, located within the trans-4-hydroxy-L
      proline metabolic gene cluster, was first successfully expressed in the host
      Pseudomonas putida. Purified HypO protein functioned as a FAD-containing cis-4
      hydroxy-D-proline dehydrogenase with a homomeric structure. In contrast to other
      known enzymes, significant activity for D-proline was found, confirming a
      previously proposed potential involvement in D-proline metabolism.

PMID- 29191114
TI  - Gene CG15630 (fipi) is involved in regulation of the interpulse interval in
      Drosophila courtship song.
AB  - To study the central pattern generators functioning, previously we identified
      genes, whose neurospecific knockdowns led to deviations in the courtship song of
      Drosophila melanogaster males. Reduced expression of the gene CG15630 caused a
      decrease in the interpulse interval. To investigate the role of CG15630, which we
      have called here fipi (factor of interpulse interval), in the courtship song
      production, at first, we have characterized fipi transcripts and protein (FIPI)
      in the mutant flies carrying P insertion and deletions in this gene and in flies
      with its RNAi knockdown. FIPI is homologous to the mammalian NCAM2 protein, an
      important factor of neuronal development in the olfactory system. In this study,
      we have revealed that local fipi knockdown in the antennal olfactory sensory
      neurons (OR67d and IR84a), which are responsible for reception of chemosignals
      modulating courtship behavior, alters the interpulse interval in the opposite
      directions. Thus, a proper fipi expression seems to be necessary for perception
      of sexual chemosignals, and the effect of fipi knockdown on IPI value depends on
      the type of chemoreceptor neurons affected.

PMID- 29191116
TI  - December 2017 Letter to the Editor-in-Chief.
AB  - Letter to the Editor-in-Chief of JOSPT as follows: "The Wider View of
      Biopsychosocial Models" with Authors' Response J Orthop Sports Phys Ther
      2017;47(12):972-973. doi:10.2519/jospt.2017.0207.

PMID- 29191115
TI  - Focal neurons: another source of vascular endothelial growth factor in brain
      arteriovenous malformation tissues?
AB  - Background Brain arteriovenous malformations (bAVMs) are devastating, hemorrhage
      prone, cerebrovascular entities characterized by well-defined feeding arteries,
      draining veins, and the absence of a capillary bed. The endothelial cells that
      comprise bAVMs exhibit a loss of arterial and venous specification. The role of
      abnormal angiogenesis in the formation and progression of bAVMs is still unclear.
      This study aimed to investigate the expression of vascular endothelial growth
      factor (VEGF) in neurons and glial cells in bAVMs to try to uncover the multiple
      cell origin of VEGF. Methods A total of 25 bAVM specimens and 25 control tissues
      were obtained. Western blot and immunohistochemical analyses were used to
      evaluate the expression of VEGF. The distribution of VEGF in neurons and glial
      cells in these bAVMs were observed by double-label immunofluorescence staining
      and subsequent imaging. Results Western blot analysis revealed a significant
      overexpression of VEGF in bAVM tissues (P < 0.05). Immunohistochemistry showed
      that the amount of cells that overexpressed VEGF in bAVM tissues was
      significantly greater compared to that in normal tissues (P < 0.05). Double-label
      immunofluorescence staining showed no significant difference between the mean
      amounts of VEGF-positive cells in astrocytes and in neurons (P < 0.05).
      Conclusions The formation and progression of bAVMs is related to the local
      overexpression of VEGF. Similar levels of VEGF overexpression are found in
      astrocytes, neurons, and vascular endothelial cells, which suggest that VEGF may
      be derived from astrocytes and neurons. It implied that focal neurons may play a
      certain role in the pathophysical process of bAVMs, however, identification of
      the production and functional mechanisms of VEGF in the neurons still requires
      further investigation.

PMID- 29191117
TI  - Addressing Intervention Fidelity Within Physical Therapy Research and Clinical
      Practice.
AB  - Intervention fidelity is a key component of the design and conduct of physical
      therapy research, defined as "the methodological strategies used to enhance and
      monitor the reliability and validity of behavioral interventions." This includes
      enhancing and assessing the extent to which an intervention is implemented as
      intended by its developers, including how they envisage the participants or
      patients to interact with the intervention. The authors of this Viewpoint focus
      predominantly on the fidelity of intervention delivery; highlight the importance
      of intervention fidelity for the physical therapy profession and its relevance
      for both physical therapy researchers and practitioners; and explore potential
      barriers to enhancing and assessing the fidelity of intervention delivery in
      physical therapy research. J Orthop Sports Phys Ther 2017;47(12):895-898.
      doi:10.2519/jospt.2017.0609.

PMID- 29191118
TI  - Spondylolisthesis Identified Using Ultrasound Imaging.
AB  - 57-year-old woman was recruited for a research study of muscle activation in
      persons with low back pain. She described a progressive worsening of left lower
      lumbar pain, which began 5 years prior without any precipitating incident, and
      intermittent pain at the left gluteal fold (diagnosed as a proximal hamstring
      tear 2 years prior). Ultrasound revealed marked anterior displacement of the L3-4
      and L4-5 facet joints. The subject was recommended for a radiograph using a
      lateral recumbent view, which demonstrated a grade II spondylolisthesis. J Orthop
      Sports Phys Ther 2017;47(12):970. doi:10.2519/jospt.2017.7363.

PMID- 29191119
TI  - Centers for Medicare and Medicaid Services Policy Regarding Supervised Exercise
      for Patients With Intermittent Claudication: The Good, the Bad, and the Ugly.
AB  - On May 25, 2017, the Centers for Medicare and Medicaid Services (CMS) issued a
      decision memo establishing coverage for supervised exercise therapy (SET) for
      Medicare beneficiaries experiencing intermittent claudication due to peripheral
      artery disease (PAD). A meaningful impact on population health is possible with
      greater freedom to participate in regular physical activity. The authors of this
      editorial explain the potential roles of physical therapists in the SET program
      and argue for further integration of physical therapists through collaborative
      practice. J Orthop Sports Phys Ther 2017;47(12):892-894.
      doi:10.2519/jospt.2017.0111.

PMID- 29191120
TI  - Thank You to All JOSPT Contributors for 2017.
AB  - On behalf of the many stakeholders in the Journal of Orthopaedic & Sports
      Physical Therapy (JOSPT), including the Sections and international partners,
      readers, Editorial Board, and authors, Editor-in-Chief J. Haxby Abbott gives
      thanks and recognizes all of the many individuals who have contributed to the
      editorial process and content of JOSPT this past year. J Orthop Sports Phys Ther
      2017;47(12):889-891. doi:10.2519/jospt.2017.0110.

PMID- 29191121
TI  - A Grade IV Isthmic Spondylolisthesis.
AB  - A 15-year-old adolescent boy was referred by an orthopaedic surgeon for treatment
      of right gluteal and thigh pain. Following treatment that reduced his pain, he
      experienced acute onset of bilateral radiculopathy. He was referred back to the
      physician, who ordered radiographs and magnetic resonance imaging, which
      identified a grade IV isthmic spondylolisthesis at the L5-S1 level. J Orthop
      Sports Phys Ther 2017;47(12):971. doi:10.2519/jospt.2017.7547.

PMID- 29191122
TI  - Association between TPMT*3C and decreased thiopurine S-methyltransferase activity
      in patients with neuromyelitis optica spectrum disorders in China.
AB  - AIM OF THE STUDY: Thiopurines are effective drugs in treating neuromyelitis
      optica spectrum disorders and other diseases. Thiopurines' toxicity is mainly
      imputed to thiopurine S-methyltransferase activity. In Chinese population, the
      most common and important variation of thiopurine S-methyltransferase is TPMT*3C
      (rs1142345). This study aims to reveal the association between thiopurine S
      methyltransferase activity and genetic polymorphisms of thiopurine S
      methyltransferase in patients with neuromyelitis optica spectrum disorders in
      China. MATERIAL AND METHODS: A liquid chromatography tandem mass/mass method was
      used to evaluate the thiopurine S-methyltransferase activity by using 6
      mercapthioprine as the substrate in human erythrocyte haemolysate via 1 h
      incubation at 37  degrees C to form its methylated product 6
      methylmercaptopurine. The amount of 6-methylmercaptopurine was adjusted by
      haematocrit and normalized to 8 * 108 erythrocytes. The selected polymorphisms of
      thiopurine S-methyltransferase were identified using MassARRAY system (Sequenom)
      and multiple SNaPshot technique. RESULTS: In 69 patients with neuromyelitis
      optica spectrum disorders, thiopurine S-methyltransferase activity was 80.29
      154.53 (127.51 +/- 16.83) pmol/h/8 * 108 erythrocytes. TPMT*3C (rs1142345) was
      associated with lower thiopurine S-methyltransferase activity (BETA = -25.37, P =
      0.011). Other selected variants were not associated with thiopurine S
      methyltransferase activity. CONCLUSIONS: TPMT*3C affects TPMT activity in Chinese
      patients with neuromyelitis optica spectrum disorders. Further studies are
      warranted to confirm the results. ABBREVIATIONS: TPRs = thiopurines; NMOSD =
      neuromyelitis optica spectrum disorders; TPMT = thiopurine S-methyltransferase;
      LC-MS/MS = liquid chromatography tandem mass/mass; 6-MMP = 6
      methylmercaptopurine; IS = internal standard; SNP = single nucleotide
      polymorphism; MAF = minor allele frequency; HWE = Hardy-Weinberg equilibrium;
      BETA = regression coefficients; UTR-3 = untranslated region 3.

PMID- 29191124
TI  - The dental manifestations and orthodontic implications of hypoparathyroidism in
      childhood.
AB  - The presence of short dental roots can present challenges to the orthodontist
      both in terms of identifying its aetiology and in subsequent treatment planning.
      Uncommon causes include hypoparathyroidism and pseudohypoparathyroidism, where
      short roots may be seen in combination with other oral manifestations including
      enamel hypoplasia secondary to low calcium levels. This case report highlights
      these features and the orthodontic treatment proposed.

PMID- 29191125
TI  - The 2017 AANS Presidential Address. A world of innovation.
AB  - The 2016 scientific meeting of the American Association of Neurological Surgeons
      (AANS) focused on the theme "A World of Innovation." In his presidential address,
      2016 AANS President Frederick Boop compared the historical development of the
      specialty of neurological surgery with that of the development of global
      communications. In the early years, general surgeons training in the United
      States would spend post-residency time abroad learning from surgical masters in
      Europe and other places. Since Harvey Cushing's day, neurosurgeons from around
      the world continue to travel abroad, with many now coming to America for training
      at centers of excellence. Current clinical practice is defined by multi-national,
      multi-center clinical trials, and the AANS subsidiary NeuroPoint Alliance has
      positioned itself to serve as an international center for the oversight of such
      trials. The Neurosurgery Research & Education Foundation and the Journal of
      Neurosurgery Publishing Group have made it possible for a neurosurgeon anywhere
      with Internet access to learn relevant surgical anatomy, learn new neurosurgical
      procedures, and watch masters in the field perform operations via high-definition
      surgical videos at no cost via learning platforms such as the Rhoton Collection,
      the Neurosurgical Atlas, and Neurosurgical Focus video supplements. At the same
      time, patients are now traveling abroad to seek medical specialty care. Although
      the globalization of health care poses certain threats, it also presents
      neurosurgeons with a world of opportunities.

PMID- 29191123
TI  - Patient Perceptions of Barriers to Self-Management of Breast Cancer-Related
      Lymphedema.
AB  - Breast cancer survivors are at lifetime risk for the development of breast cancer
      related lymphedema, a chronic, potentially debilitating condition that requires
      life-long symptom management. Suboptimal self-management rates suggest that
      health care providers may not be offering educative-support options that are
      customized to patient-perceived needs. An Institutional Review Board-approved
      focus group ( N = 9) and mailed surveys ( N = 15) were used to identify (a)
      barriers to lymphedema self-management, (b) how breast cancer survivors with
      lymphedema defined education and support, (c) what type of education and support
      they had received, and (d) what kind of education and support they wanted.
      Physiological, psychological, and psychosocial factors were identified as
      barriers to successful lymphedema self-management. One of the main barriers
      identified was lack of education about lymphedema treatment and risk reduction.
      In addition, more than half defined support as "prescriptions" and "referrals";
      therefore, it is unclear whether patients were exposed to support other than
      medical treatment.

PMID- 29191126
TI  - Intravesical radiofrequency induced hyperthermia enhances mitomycin C
      accumulation in tumour tissue.
AB  - INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a highly recurrent
      disease with potential progression to muscle invasive disease despite the
      standard bladder instillations with mitomycin C (MMC) or Bacille Calmette-Guerin
      immunotherapy. Therefore, alternatives such as radiofrequency-induced
      chemohyperthermia (RF-CHT) with MMC are being investigated. The mechanism
      explaining the efficacy of RF-CHT is only partly understood. We examined whether
      RF-CHT results in higher MMC tissue concentrations as compared to cold MMC
      instillation. PATIENTS AND METHODS: Prior to a planned transurethral resection of
      bladder tumour (TURBT), patients with stage Ta NMIBC were allocated to either (1)
      cold MMC instillation or (2) RF-CHT. After MMC instillation, three biopsies were
      taken of both normal and tumour tissue. Biopsies were snap-frozen and MMC tissue
      concentrations were analysed using ultra-performance liquid chromatography.
      RESULTS: Eleven patients were included of which six received RF-CHT. Ten patients
      had TaG2-LG/HG papillary tumours at pathology. One patient in the RF-CHT group
      appeared to be free of malignancy and was excluded from the analysis as no tumour
      biopsies were available. The median MMC concentration in tumour tissue was higher
      in the RF-CHT group (median 665.00 ng/g vs. 63.75 ng/g, U = 51.0, p = 0.018).
      Moreover, in both techniques the MMC concentration was lower in normal tissue
      compared to tumour tissue. Tissue MMC concentration measurements varied
      substantially within, and between, different patients from the same group.
      CONCLUSION: Intravesical RF-CHT results in higher tumour MMC concentrations vs.
      cold MMC instillation which contributes to its superior efficacy.

PMID- 29191127
TI  - The association between the environmental endocrine disruptor bisphenol A and
      polycystic ovary syndrome: a systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate the association between bisphenol A (BPA) and
      polycystic ovary syndrome (PCOS). METHODS: A systematic review and meta-analysis
      using STATA software for observational studies. RESULTS: Nine studies involving
      493 PCOS patients and 440 controls were included in this review. The meta
      analysis demonstrated that PCOS patients had significantly higher BPA levels
      compared with control groups (standardized mean difference (SMD): 2.437, 95%
      confidence interval (CI): (1.265, 3.609), p < .001). For studies of serum samples
      detected by enzyme-linked immunosorbent assay (ELISA), subgroup analyses
      according to ethnicity, body mass index (BMI), sample size, detection method
      (high-performance liquid chromatography (HPLC) and ELISA), PCOS-to-control ratio
      and study quality displayed that high BPA levels were significantly associated
      with Caucasian PCOS patients (SMD: 0.615, 95% CI: (0.308, 0.922), p < .001), high
      BMI (SMD: 0.512, 95% CI: (0.180, 0.843), p = .002), high quality (SMD: 0.624, 95%
      CI: (0.391, 0.856), p < .001), and high HOMA-IR (SMD: 0.467, 95% CI: (0.121,
      0.813), p = .008). CONCLUSIONS: Serum BPA may be positively associated with women
      with PCOS and BPA might be involved in the insulin-resistance and
      hyperandrogenism of PCOS. More evidence from high quality studies, advanced
      detection methods, and larger cohorts for observational trials are needed to
      further confirm the association between BPA and PCOS.

PMID- 29191128
TI  - Suppressive effect of nobiletin and epicatechin gallate on fructose uptake in
      human intestinal epithelial Caco-2 cells.
AB  - Inhibition of excessive fructose intake in the small intestine could alleviate
      fructose-induced diseases such as hypertension and non-alcoholic fatty liver
      disease. We examined the effect of phytochemicals on fructose uptake using human
      intestinal epithelial-like Caco-2 cells which express the fructose transporter,
      GLUT5. Among 35 phytochemicals tested, five, including nobiletin and epicatechin
      gallate (ECg), markedly inhibited fructose uptake. Nobiletin and ECg also
      inhibited the uptake of glucose but not of L-leucine or Gly-Sar, suggesting an
      inhibitory effect specific to monosaccharide transporters. Kinetic analysis
      further suggested that this reduction in fructose uptake was associated with a
      decrease in the apparent number of cell-surface GLUT5 molecules, and not with a
      change in the affinity of GLUT5 for fructose. Lastly, nobiletin and ECg
      suppressed the permeation of fructose across Caco-2 cell monolayers. These
      findings suggest that nobiletin and ECg are good candidates for preventing
      diseases caused by excessive fructose intake.

PMID- 29191129
TI  - Subcellular localization of aphidicolin biosynthetic enzymes heterologously
      expressed in Aspergillus oryzae.
AB  - The secondary metabolite aphidicolin has previously been produced by Aspergillus
      oryzae after the heterologous expression of four biosynthetic enzymes isolated
      from Phoma betae. In this study, we examined the subcellular localization of
      aphidicolin biosynthetic enzymes in A. oryzae. Fusion of green fluorescent
      protein to each enzyme showed that geranylgeranyl diphosphate synthase and
      terpene cyclase are localized to the cytoplasm and the two monooxygenases (PbP450
      1 and PbP450-2) are localized to the endoplasmic reticulum (ER). Protease
      protection assays revealed that the catalytic domain of both PbP450s was
      cytoplasmic. Deletion of transmembrane domains from both PbP450s resulted in the
      loss of ER localization. Particularly, a PbP450-1 mutant lacking the
      transmembrane domain was localized to dot-like structures, but did not colocalize
      with any known organelle markers. Aphidicolin biosynthesis was nearly abrogated
      by deletion of the transmembrane domain from PbP450-1. These results suggest that
      ER localization of PbP450-1 is important for aphidicolin biosynthesis.

PMID- 29191130
TI  - Structural and functional analysis of the carotenoid biosynthesis genes of a
      Pseudomonas strain isolated from the excrement of Autumn Darter.
AB  - There are many reports about carotenoid-producing bacteria and carotenoid
      biosynthesis genes. In databases for Pseudomonas genome sequences, there are
      genes homologous to carotenoid biosynthesis genes, but the function of these
      genes in Pseudomonas has not been elucidated. In this study, we cloned the
      carotenoid biosynthesis genes from a Pseudomonas sp. strain, named Akiakane,
      which was isolated from the excrement of the Autumn Darter dragonfly. Using an
      Escherichia coli functional expression system, we confirmed that the idi, crtE,
      crtB, crtI, and crtY gene products of the Akiakane strain show predictable
      catalytic activities. A cluster of six genes was also found, which was comparable
      to other carotenoid-producing bacteria that belong to the alpha-Proteobacteria or
      gamma-Proteobacteria class.

PMID- 29191131
TI  - Efficacy of ceftazidime-avibactam in a rat intra-abdominal abscess model against
      a ceftazidime- and meropenem-resistant isolate of Klebsiella pneumoniae carrying
      blaKPC-2.
AB  - Efficacies of ceftazidime-avibactam (4:1 w/w) and ceftazidime were tested against
      ceftazidime-susceptible (blaKPC-2-negative), and meropenem- and ceftazidime
      resistant (blaKPC-2-positive), Klebsiella pneumoniae in a 52-h, multiple dose,
      abdominal abscess model in the rat. Efficacies corresponded to minimum inhibitory
      concentrations (MICs) measured in vitro and were consistent with drug exposures
      modelled from pharmacokinetics in infected animals. The ceftazidime, ceftazidime
      avibactam and meropenem control treatments were effective in the rat abscess
      model against the susceptible strain, whereas only ceftazidime-avibactam was
      effective against K. pneumoniae harbouring blaKPC-2.

PMID- 29191132
TI  - Severe Disseminated Necrotizing and Granulomatous Lymphadenitis and Encephalitis
      in a Dog Due to Sporotrichum pruinosum (Teleomorph: Phanerochaete chrysosporium).
AB  - A 9-year-old female mixed breed dog presented for an acute onset of anorexia,
      vomiting, and cough. Initial examination and diagnostics revealed a large
      multilobular cranial mediastinal mass with unidentified fungal organisms on
      cytology. The disease progressed in spite of therapy until the dog was euthanized
      8 months later. Gross necropsy findings were a large multilobular intrathoracic
      mass, mild pleuritis, and generalized lymphadenopathy. Histologic evaluation
      showed granulomatous inflammation and necrosis with numerous 20- to 70-micron,
      periodic acid-Schiff- and Gomori methenamine silver-positive spherules effacing
      lymph node parenchyma, as well as severe inflammation within the midbrain.
      Endosporulation was a common finding, and large numbers of fungal hyphae were
      also present in affected areas. Ribosomal RNA gene sequencing found 100% identity
      to published sequences of Phanerochaete chrysosporium, the teleomorph form of
      Sporotrichum pruinosum. This is the first published report of disease caused by
      natural infection with this basidiomycete organism in animals.

PMID- 29191133
TI  - Focal Segmental Glomerulosclerosis in Related Miniature Schnauzer Dogs.
AB  - Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a
      common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs
      in particular. This study describes the morphologic features present in the
      kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS,
      characterized by solidification of portions of the capillary tuft, affected 32%
      to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by
      hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in
      older dogs. Seven of 8 dogs had arteriolar hyalinosis. Ultrastructurally, all
      dogs had evidence of a podocytopathy in the absence of electron-dense deposits,
      glomerular basement membrane splitting, or fibrils. All dogs had multifocal to
      extensive podocyte foot process effacement. Other podocyte changes included
      microvillous transformation, the presence of vacuoles or protein resorption
      droplets, cytoplasmic electron-dense aggregates, and occasional binucleation.
      Variable amounts of intraglomerular lipid were present in all dogs. All dogs were
      proteinuric, with measured values for the urine protein-to-creatinine ratio
      ranging from 1.2 to 6.5. Azotemia was mild to absent and dogs were euthanatized
      at 5.1 to 14 years of age, in all cases due to nonrenal diseases. The underlying
      cause of FSGS in these Miniature Schnauzer dogs has yet to be determined, but
      contributors likely include genetic podocytopathy, lipid abnormalities, and
      glomerular hypertension.

PMID- 29191135
TI  - Message Framing and Engagement in Specialty Mental Health Care.
AB  - OBJECTIVE: Engagement rates in specialty mental health care for depression are
      suboptimal. This study examined the extent to which framing-by gain, by loss, or
      neutral- of health messages promotes appointment attendance among patients
      referred to specialty mental health care. METHODS: The study employed a
      randomized, prospective, experimental design. Patients meeting criteria for major
      depression and referred to specialty mental health care at the Corporal Michael
      J. Crescenz Department of Veterans Affairs Medical Center were randomly assigned
      (N=360) to receive a patient reminder letter routinely mailed prior to scheduled
      specialty care appointments (neutral) or one of two messages (gain framed versus
      loss framed) that were added to the routine letter. Appointment and attendance
      data were extracted from the computerized system. Logistic regression was used to
      determine the association between message frame condition and initial appointment
      attendance. RESULTS: The sample (mean+/-SD age=51.5+/-13.5) was primarily male
      (85%) and nonwhite (62%), and the mean depressive symptom score indicated
      moderately severe depression. Participants who received the gain-framed message
      after being referred to specialty mental health care were significantly more
      likely to attend their appointment than those who received a neutral letter
      (p=.04). No statistically significant differences were noted among those
      receiving a loss-framed message compared with the other two arms. CONCLUSIONS:
      Findings suggest that highlighting the benefits of attending an initial specialty
      mental health care appointment, even if in writing, can affect engagement rates.
      If replicated, results have the potential to improve mental health treatment
      initiation rates in a timely, efficient, and cost-effective manner.

PMID- 29191134
TI  - Safety Evaluation of Lipid Nanoparticle-Formulated Modified mRNA in the Sprague
      Dawley Rat and Cynomolgus Monkey.
AB  - The pharmacology, pharmacokinetics, and safety of modified mRNA formulated in
      lipid nanoparticles (LNPs) were evaluated after repeat intravenous infusion to
      rats and monkeys. In both species, modified mRNA encoding the protein for human
      erythropoietin (hEPO) had predictable and consistent pharmacologic and
      toxicologic effects. Pharmacokinetic analysis conducted following the first dose
      showed that measured hEPO levels were maximal at 6 hours after the end of
      intravenous infusion and in excess of 100-fold the anticipated efficacious
      exposure (17.6 ng/ml) at the highest dose tested.24 hEPO was pharmacologically
      active in both the rat and the monkey, as indicated by a significant increase in
      red blood cell mass parameters. The primary safety-related findings were caused
      by the exaggerated pharmacology of hEPO and included increased hematopoiesis in
      the liver, spleen, and bone marrow (rats) and minimal hemorrhage in the heart
      (monkeys). Additional primary safety-related findings in the rat included mildly
      increased white blood cell counts, changes in the coagulation parameters at all
      doses, as well as liver injury and release of interferon gamma-inducible protein
      10 in high-dose groups only. In the monkey, as seen with the parenteral
      administration of cationic LNPs, splenic necrosis and lymphocyte depletion were
      observed, accompanied with mild and reversible complement activation. These
      findings defined a well-tolerated dose level above the anticipated efficacious
      dose. Overall, these combined studies indicate that LNP-formulated modified mRNA
      can be administered by intravenous infusion in 2 toxicologically relevant test
      species and generate supratherapeutic levels of protein (hEPO) in vivo.

PMID- 29191136
TI  - Use of a Mental Health Center Collaborative Care Team to Improve Diabetes Care
      and Outcomes for Patients With Psychosis.
AB  - OBJECTIVE: This study aimed to evaluate the feasibility, acceptability, and
      preliminary effectiveness (compared with usual care) of a collaborative care
      model to treat community mental health center (CMHC) patients with psychosis and
      poorly controlled diabetes. METHODS: Stakeholder input was used to adapt a
      primary care-based collaborative care intervention for CMHC settings. Thirty-five
      adult CMHC clients with type II diabetes and hemoglobin A1c (HbA1c) >8% or blood
      pressure >140/90 were randomized to receive either collaborative care or usual
      care. Change in HbA1c was evaluated between baseline and three months. Paired t
      tests were used for within-group comparisons. RESULTS: After three months,
      intervention participants had a statistically significant mean decrease in HbA1c
      of 1.1% (p=.049). There was no significant change in HbA1c in the usual-care
      group. CONCLUSIONS: This pilot demonstrates the feasibility and acceptability of
      implementing collaborative care in CMHC settings and its preliminary
      effectiveness in improving glycemic control in a high-risk population.

PMID- 29191137
TI  - Racial-Ethnic Differences in Patterns of Discontinuous Medication Treatment Among
      Medicaid-Insured Youths With ADHD.
AB  - OBJECTIVE: This study examined the association between race-ethnicity and
      patterns of medication gaps and discontinuities among Medicaid-insured children
      initiating pharmacotherapy for attention-deficit hyperactivity disorder (ADHD).
      METHODS: Medicaid claims data from nine states were used to identify racial
      ethnic differences in patterns of ADHD medication treatment among 102,669
      children initiating ADHD medication. Multinomial logistic regression with state
      indicators was used to estimate these differences, with adjustment for individual
      and contextual confounders. RESULTS: Approximately three-fifths of the sample did
      not receive continuous medication treatment as defined by HEDIS guidelines; among
      them, one-fifth discontinued treatment with no subsequent reinitiation (early
      termination), less than one-tenth reinitiated pharmacotherapy following a single
      medication gap, more than three-tenths experienced discontinuous pharmacotherapy
      with two gaps, and more than four-tenths experienced discontinuous
      pharmacotherapy with three or more gaps. Compared with white children, black
      children had a 25% relative increase in the likelihood of early termination and
      Hispanic children had a 21% relative increase (p<.001); their relative increases
      in the likelihood of two medication gaps were 41% and 29%, respectively (p<.001),
      and for three or more gaps they were 56% and 40%, respectively (p<.001).
      CONCLUSIONS: Black and Hispanic children were much more likely than white
      children to be classified as discontinuing ADHD medication treatment, according
      to HEDIS. The differences predominantly occurred because youths from minority
      groups were more likely to experience multiple medication gaps, rather than
      complete discontinuation. Future studies should examine reasons for these
      multiple gaps to inform interventions to improve ADHD treatment continuity.

PMID- 29191138
TI  - Differential Reimbursement of Psychiatric Services by Psychiatrists and Other
      Medical Providers.
AB  - OBJECTIVE: Given low psychiatrist participation in insurance networks, this study
      examines how psychiatrists are reimbursed in network and out of network under
      commercial insurance relative to other providers for the same diagnoses and
      services. METHODS: Paid private insurance claims from the 2014 Truven Health
      Analytics MarketScan Commercial Claims and Encounters Database were analyzed. The
      sample included all services billed for 3.8 million individuals with a mental
      disorder as the primary diagnosis by psychiatrists, nonpsychiatrist medical
      doctors, psychologists, social workers, or psychiatric nurses. The authors
      determined the most common services provided by each provider type, the median
      reimbursement and median out-of-pocket payment for the services by provider type
      and by network status (in or out of network), and the proportion of bills for
      services delivered out of network. RESULTS: "Evaluation and management" services
      for presenting problems of low to moderate and moderate to high severity were the
      two procedures most frequently billed by psychiatrists and nonpsychiatrist
      medical doctors. The median reimbursement for services for presenting problems of
      low to moderate and moderate to high severity was 13% less ($66 versus $76) and
      20% less ($91 versus $114), respectively, for psychiatrists versus
      nonpsychiatrist medical doctors if the services were provided in network but 28%
      higher ($100 versus $78) and 6% higher ($122 versus $115), respectively, for
      psychiatrists versus nonpsychiatrist medical doctors for services provided out of
      network. CONCLUSIONS: Psychiatrists receive lower in-network reimbursement than
      nonpsychiatrist medical doctors for many of the same services. This may
      contribute to psychiatrists' lower participation in insurance networks relative
      to other providers and has implications for patient cost sharing and access to
      psychiatrists.

PMID- 29191139
TI  - Potential Benefits to Patients and Payers From Increased Measurement of
      Antipsychotic Plasma Levels in the Management of Schizophrenia.
AB  - Approximately 40% of patients with schizophrenia either do not respond to the
      prescribed antipsychotic drug or cannot tolerate it because of side effects,
      resulting in poor disease control and negative health and economic outcomes.
      Identifying the root cause of such complicated courses of treatment is a critical
      step in the treatment of these patients. Although measurement of antipsychotic
      plasma levels can be used to discern potential root causes, this tool is not
      routinely used in the United States. The authors of this column discuss the
      potential effects on patient outcomes and on the value of care from greater use
      of this diagnostic tool, especially under emerging payment models and delivery
      system reform efforts.

PMID- 29191140
TI  - Management of Common Medical Conditions by Office-Based Psychiatrists.
AB  - OBJECTIVE: This study examined the extent of psychiatrists' involvement in
      general medical management activities for their patients. METHODS: With data from
      the 2006-2013 U.S. National Ambulatory Medical Survey-an annual cross-sectional
      survey of visits in a random week to office-based physicians-general medical
      management activities in 11,046 visits to psychiatrists, 66,267 to general
      medical physicians (general and family physicians and internists), and 158,933 to
      other physicians were compared. General medical management activities included
      recordings of hypertension, hyperlipidemia, diabetes, or obesity; prescriptions
      of medications for hypertension, hyperlipidemia, or diabetes; blood pressure or
      weight measurements; ordering glucose, glycohemoglobin (HbA1c), lipids, or
      cholesterol laboratory tests; and education or counseling for weight, exercise,
      diet and nutrition, or tobacco use. RESULTS: Any of the target general medical
      management activities were provided in 37.0% of visits to psychiatrists, compared
      with 98.0% of visits to general medical physicians and 78.4% to other physicians.
      Differences between psychiatrists and all other physician groups were smaller for
      health education and counseling. For each general medical management activity,
      many of the psychiatrists did not engage in the activity in any of their sampled
      visits. The most consistent predictors of general medical management activities
      in each psychiatrist visit were the extent of these activities in other visits to
      the same psychiatrist and having recorded other types of general medical
      management activities in the same visit. CONCLUSIONS: Efforts to expand
      psychiatric practice to general medical management activities require better
      understanding of barriers to such expansion, better characterization of
      conditions under which such expansion is feasible, and continuing medication
      education.

PMID- 29191141
TI  - Person-Oriented Recovery of Individuals With Serious Mental Illnesses: A Review
      and Meta-Analysis of Longitudinal Findings.
AB  - OBJECTIVE: Although there is significant literature examining changes over time
      in the functional recovery of people with serious mental illnesses, relatively
      little is known about the longitudinal nature of person-oriented recovery. The
      purpose of this review and meta-analysis is to synthesize findings pertaining to
      the study of person-oriented recovery constructs over time and concomitants of
      change. METHODS: Systematic searches up to February 2017 were conducted and were
      supplemented by hand-searching of reference lists and by contacting study
      authors. Twenty-three independent studies that included a sample of individuals
      with serious mental illnesses and that quantitatively measured person-oriented
      recovery, empowerment, or hope over at least two time points were included in the
      review. Of these, seven were randomized controlled trials that were included in
      the meta-analysis. Data were independently extracted by two reviewers. Aggregate
      effect sizes for person-oriented recovery outcomes were calculated, and
      individual, intervention, and methodological characteristics served as moderators
      in meta-regression analyses. RESULTS: The meta-analysis (N=1,739 participants)
      demonstrated that consumers experience greater (and sustained) improvement in
      person-oriented recovery outcomes when they are involved in recovery-oriented
      mental health treatment versus usual care or other types of treatment. Only type
      of intervention provider was a significant moderator; a study of an intervention
      that was delivered by both mental health professionals and peer providers
      demonstrated the greatest differences between treatment and control groups.
      CONCLUSIONS: Recovery-focused interventions, especially those that involve
      collaborations between mental health professionals and peer providers, may serve
      to foster increased recovery, hope, and empowerment among individuals with
      serious mental illnesses.

PMID- 29191142
TI  - Forensic Experts, Indigent Defendants, and the Constitution.
AB  - Over 30 years ago, the U.S. Supreme Court held that indigent defendants raising
      psychiatric issues are entitled to the assistance of a mental health expert.
      However, the exact dimensions of that assistance, and whether the expert must be
      assigned exclusively to assist the defense, have been in contention ever since.
      In its recent decision in McWilliams v. Dunn, the Court underscored that the
      state-funded expert must be available to consult with the defense, not merely to
      evaluate the defendant, but declined to opine on whether the defense is entitled
      to its own expert for the purpose.

PMID- 29191143
TI  - A crude sword bean (Canavalia gladiata) extract is gelated by cooling.
AB  - White sword bean (Canavalia gladiata) seeds have the potential to be utilized in
      the manufacturing of processed foods owing to their high protein and carbohydrate
      content. Our previous reports explored the use of the sword bean as a source of
      food materials by preparing extracts in distilled water. In the present study, we
      found that one such extract can be gelated by cooling. The gelling substances
      were extracted by boiling and simultaneously stirring a suspension containing
      ground beans. Few proteins were present in the gelated extract. We also examined
      the conditions under which gelation occurred and the gel melting temperature. The
      extract gelated at temperatures below 10  degrees C, and the resulting gel melted
      at those above 65  degrees C. This is the first report that gelling substances
      can be extracted from sword beans in large quantities. We expect that this
      gelling agent can be used for the production of processed foods.

PMID- 29191145
TI  - Predictors of Staff Attitudes Toward Schizophrenia Treatments.

PMID- 29191146
TI  - Code.

PMID- 29191144
TI  - Implementing Integrated Mental Health and Chaplain Care in a National Quality
      Improvement Initiative.
AB  - This column describes the development, implementation, and outcomes of a quality
      improvement learning collaborative that aimed to better integrate chaplaincy with
      mental health care services at 14 participating health care facilities evenly
      distributed across the U.S. Department of Veterans Affairs and Department of
      Defense. Teams of health care chaplains and mental health professionals from
      participating sites sought to improve cross-disciplinary service integration in
      six key domains: screening, referrals, assessment, communication and
      documentation, cross-disciplinary training, and role clarification. Chaplains and
      mental health providers across all facilities at participating sites were
      significantly more likely post-collaboration to report having a clear
      understanding of how to collaborate and to report using a routine process for
      screening patients who could benefit from seeing a professional from the other
      discipline. Foundational efforts to enhance cross-disciplinary awareness and
      screening practices between chaplains and mental health professionals appear
      particularly promising.

PMID- 29191147
TI  - The SWEET Life: Improving Treatment Engagement and Emotional Wellness in Diverse
      Clinical Populations.

PMID- 29191148
TI  - A Workshop to Engage Community Stakeholders to Deliver Evidence-Based Treatment
      for Hoarding Disorder: A Pilot Study.

PMID- 29191149
TI  - When Will Telepsychiatry Reach Its "Tipping Point"?

PMID- 29191150
TI  - Effectiveness of Community Treatment Orders? Two Studies With Unusual Outcomes
      and an Atypical Population.

PMID- 29191152
TI  - The impact of socioeconomic factors on municipal solid waste generation in Sao
      Paulo, Brazil.
AB  - Social factors have not been sufficiently explored in municipal solid waste
      management studies. Latin America has produced even fewer studies with this
      approach; technical and economic investigations have prevailed. We explored the
      impacts of socioeconomic factors on municipal solid waste generation in Greater
      Sao Paulo, which includes 39 municipalities. We investigated the relations
      between municipal solid waste generation and social factors by Pearson's
      correlation coefficient. The Student's t-test (at p <- 0.01) proved significance,
      and further regression analysis was performed with significant factors. We
      considered 10 socioeconomic factors: population, rural population, density, life
      expectancy, education (secondary, high and undergraduate level), income per
      capita, inequality and human development. A later multicollinearity analysis
      resulted in the determination of inequality (rp = 0.625) and income per capita
      (rp = 0.607) as major drivers. The results showed the relevance of considering
      social aspects in municipal solid waste management and isolated inequality as an
      important factor in planning. Inequality must be used as a complementary factor
      to income, rather than being used exclusively. Inequality may explain differences
      of waste generation between areas with similar incomes because of consumption
      patterns. Therefore, unequal realities demand unequal measures to avoid
      exacerbation, for example, pay-as-you-throw policies instead of uniform fees.
      Unequal realities also highlight the importance of tiering policies beyond the
      waste sector, such as sustainable consumption.

PMID- 29191153
TI  - The effect of specially designed and managed occlusal devices on patient symptoms
      of tinnitus: A cohort study.
AB  - Objective Bioesthetic maxillary anterior guided orthoses (BMAGOs) were designed
      and adjusted to establish the mandibular location referred to as stable seated
      condylar position SSCP. This study demonstrates treatment efficacy of this device
      on tinnitus. Methods All patients had histories of temporomandibular disorder
      (TMD), head, neck and shoulder pain. Each patient wore the BMAGO at all times,
      eating, talking and sleeping with it functioning as a surrogate occlusion.
      Patients were seen every two weeks for adjustments. They were provided a self
      reporting numeric rating scale (NRS) beginning each visit. NRS scores ranged from
      0 to 10, with 10 being the highest intensity pain for 12 TMD symptoms including
      tinnitus. Results A significant decrease of tinnitus symptoms (p<.001) were
      recorded for all effected patients by visit #12. Conclusions These findings
      firmly support symptomatic reduction of tinnitus.

PMID- 29191154
TI  - Hepatitis C testing and re-testing among people attending sexual health services
      in Australia, and hepatitis C incidence among people with human immunodeficiency
      virus: analysis of national sentinel surveillance data.
AB  - BACKGROUND: Direct acting antivirals are expected to drastically reduce the
      burden of hepatitis C virus (HCV) in people living with Human Immunodeficiency
      Virus (HIV). However, rates of HCV testing, re-testing and incident infection in
      this group remain uncertain in Australia. We assessed trends in HCV testing, re
      testing and incident infection among HIV-positive individuals, and evaluated
      factors associated with HCV re-testing and incident infection. METHODS: The study
      population consisted of HIV-positive individuals who visited a sexual health
      service involved in the Australian Collaboration for Coordinated Enhanced
      Sentinel Surveillance (ACCESS) between 2007 and 2015. Poisson regression was used
      to assess trends and to evaluate factors associated with HCV re-testing and
      incident HCV infection. RESULTS: There were 9227 HIV-positive individuals
      included in our testing rate analysis. Of 3799 HIV-positive/HCV-negative people
      that attended an ACCESS sexual health service more than once, 2079 (54.7%) were
      re-tested for HCV and were therefore eligible for our incidence analysis. The
      rate of HCV testing increased from 17.1 to 51.4 tests per 100 patient years
      between 2007 and 2015 (p for trend <0.01). Over the same period, HCV re-testing
      rates increased from 23.9 to 79.7 tests per 100 person years (p for trend <0.01).
      A clear increase in testing and re-testing began after 2011. Patients who
      identified as men who have sex with men and those with a history of injecting
      drug use experienced high rates of HCV re-testing over the course of the study
      period. Among those who re-tested, 157 incident HCV infections occurred at a rate
      of 2.5 events per 100 person years. Between 2007 and 2009, 2010-2011, 2012-2013
      and 2014-2015, rates of incident HCV were 0.8, 1.5, 3.9 and 2.7 events per 100
      person years, respectively (p for trend <0.01). Incident HCV was strongly
      associated with a history of injecting drug use. CONCLUSIONS: High rates of HCV
      testing and re-testing among HIV-positive individuals in Australia will assist
      strategies to achieve HCV elimination through rapid treatment scale up. Continued
      monitoring of HCV incidence in this population is essential for guiding both HCV
      prevention and treatment strategies.

PMID- 29191155
TI  - Provider initiated tuberculosis case finding in outpatient departments of health
      care facilities in Ghana: yield by screening strategy and target group.
AB  - BACKGROUND: Meticulous identification and investigation of patients presenting
      with tuberculosis (TB) suggestive symptoms rarely happen in crowded outpatient
      departments (OPDs). Making health providers in OPDs diligently follow screening
      procedures may help increase TB case detection. From July 2010 to December 2013,
      two symptom based TB screening approaches of varying cough duration were used to
      screen and test for TB among general outpatients, PLHIV, diabetics and contacts
      in Accra, Ghana. METHODS: This study was a retrospective analysis comparing the
      yield of TB cases using two different screening approaches, allocated to selected
      public health facilities. In the first approach, the conventional 2 weeks cough
      duration with or without other TB suggestive symptoms was the criterion to test
      for TB in attendants of 7 general OPDs. In the second approach the screening
      criteria cough of >24 hours, as well as a history of at least one of the
      following symptoms: fever, weight loss and drenching night sweats were used to
      screen and test for TB among attendants of 3 general OPDs, 7 HIV clinics and 2
      diabetes clinics. Contact investigation was initiated for index TB patients. The
      facilities documented the number of patients verbally screened, with presumptive
      TB, tested using smear microscopy and those diagnosed with TB in order to
      calculate the yield and number needed to screen (NNS) to find one TB case. Case
      notification trends in Accra were compared to those of a control area. RESULTS:
      In the approach using >24-hour cough, significantly more presumptive TB cases
      were identified among outpatients (0.82% versus 0.63%), more were tested (90.1%
      versus 86.7%), but less smear positive patients were identified among those
      tested (8.0% versus 9.4%). Overall, all forms of TB cases identified per 100,000
      screened were significantly higher in the >24-hour cough approach at OPD (92.7
      for cough >24 hour versus 82.7 for cough >2 weeks ), and even higher in diabetics
      (364), among contacts (693) and PLHIV (995). NNS (95% Confidence Interval) varied
      from 100 (93-109) for PLHIV, 144 (112-202) for contacts, 275 (197-451) for
      diabetics and 1144 (1101-1190) for OPD attendants. About 80% of the TB cases were
      detected in general OPDs. Despite the intervention, notifications trends were
      similar in the intervention and control areas. CONCLUSION: The >24-hour cough
      approach yielded more TB cases though required TB testing for a larger number of
      patients. The yield of TB cases per 100,000 population screened was highest among
      PLHIV, contacts, and diabetics, but the majority of cases were detected in
      general OPDs. The intervention had no discernible impact on general case
      notification.

PMID- 29191156
TI  - Pre-pregnancy BMI, gestational weight gain and risk of preeclampsia: a birth
      cohort study in Lanzhou, China.
AB  - BACKGROUND: To evaluate the independent and joint effects of maternal pre
      pregnancy BMI and gestational weight gain (GWG) on the risk of preeclampsia and
      its subtypes. METHODS: A birth cohort study was conducted from 2010 to 2012 in
      Lanzhou, China. Three hundred fourty seven pregnant women with preeclampsia and
      9516 normotensive women at Gansu Provincial Maternity and Child Care Hospital
      were included in the present study. Unconditional logistic regression models were
      used to evaluate the associations between pre-pregnancy BMI, GWG, and risk of
      preeclampsia and its subtypes. RESULTS: Compared to women with normal pre
      pregnancy BMI, those who were overweight/obese had an increased risk of
      preeclampsia (OR = 1.81; 95%CI: 1.37-2.39). Women with excessive GWG had an
      increased risk of preeclampsia (OR = 2.28; 95%CI: 1.70-3.05) compared to women
      with adequate GWG. The observed increased risk was similar for mild-, severe- and
      late-onset preeclampsia. No association was found for early-onset preeclampsia.
      Overweight/obese women with excessive GWG had the highest risk of developing
      preeclampsia compared to normal weight women with no excessive weight gain (OR =
      3.78; 95%CI: 2.65-5.41). CONCLUSIONS: Our results suggested that pre-pregnancy
      BMI and GWG are independent risk factors for preeclampsia and that the risk might
      vary by preeclampsia subtypes. Our study also proposed a potential synergistic
      effect of pre-pregnancy BMI and GWG that warrants further investigation.

PMID- 29191157
TI  - Genome-wide analysis of the Solanum tuberosum (potato) trehalose-6-phosphate
      synthase (TPS) gene family: evolution and differential expression during
      development and stress.
AB  - BACKGROUND: Trehalose-6-phosphate synthase (TPS) serves important functions in
      plant desiccation tolerance and response to environmental stimuli. At present, a
      comprehensive analysis, i.e. functional classification, molecular evolution, and
      expression patterns of this gene family are still lacking in Solanum tuberosum
      (potato). RESULTS: In this study, a comprehensive analysis of the TPS gene family
      was conducted in potato. A total of eight putative potato TPS genes (StTPSs) were
      identified by searching the latest potato genome sequence. The amino acid
      identity among eight StTPSs varied from 59.91 to 89.54%. Analysis of dN/dS ratios
      suggested that regions in the TPP (trehalose-6-phosphate phosphatase) domains
      evolved faster than the TPS domains. Although the sequence of the eight StTPSs
      showed high similarity (2571-2796 bp), their gene length is highly differentiated
      (3189-8406 bp). Many of the regulatory elements possibly related to
      phytohormones, abiotic stress and development were identified in different TPS
      genes. Based on the phylogenetic tree constructed using TPS genes of potato, and
      four other Solanaceae plants, TPS genes could be categorized into 6 distinct
      groups. Analysis revealed that purifying selection most likely played a major
      role during the evolution of this family. Amino acid changes detected in specific
      branches of the phylogenetic tree suggests relaxed constraints might have
      contributed to functional divergence among groups. Moreover, StTPSs were found to
      exhibit tissue and treatment specific expression patterns upon analysis of
      transcriptome data, and performing qRT-PCR. CONCLUSIONS: This study provides a
      reference for genome-wide identification of the potato TPS gene family and sets a
      framework for further functional studies of this important gene family in
      development and stress response.

PMID- 29191158
TI  - The miR172c-NNC1 module modulates root plastic development in response to salt in
      soybean.
AB  - BACKGROUND: Plant roots are highly plastic to high salinity. However, the
      molecular mechanism by which root developmental plasticity is regulated remains
      largely unknown. Previously we reported that miR172c-NNC1 module plays a key role
      in soybean-rhizobial symbiosis. The fact that the miR172c promoter contains
      several stress-related cis elements indicates that miR172c may have a role in
      root response to abiotic stress. RESULTS: Here we showed that miR172c is greatly
      induced by salt stress in soybean. Overexpression of miR172c and knockdown of
      miR172c activity resulted in substantially increased and reduced root sensitivity
      to salt stress, respectively. Furthermore, we show that the target gene NNC1
      (Nodule Number Control 1) of miR172c was downregulated by salt stress. The
      transgenic roots overexpressing or knocking down NNC1 expression also exhibited
      the altered root sensitivity to salt stress. CONCLUSION: The study reveals the
      crucial role of miR172c-NNC1 module in root stress tolerance to salt stress in
      soybean.

PMID- 29191159
TI  - Barriers and facilitating factors related to use of early warning score among
      acute care nurses: a qualitative study.
AB  - BACKGROUND: The early warning score (EWS) was developed to identify deteriorating
      patients early. It is a track-and-trigger system based on vital signs designed to
      direct appropriate clinical responses based on the seriousness and nature of the
      underlying condition. Despite its wide dissemination, serious adverse events
      still occur, often due to failure among staff on general wards to follow the EWS
      protocol. The purpose of the study was to determine barriers and facilitating
      factors related to three aspects of the EWS protocol: 1) adherence to monitoring
      frequency, 2) call for junior doctors to patients with an elevated EWS, and 3)
      call for the medical emergency team. METHODS: Focus groups were conducted with
      nurses from medical and surgical acute care wards, and content analysis was used
      to identify barriers and facilitating factors in relation to the research
      questions. RESULTS: Adherence to monitoring frequency would frequently be set
      aside during busy periods for other tasks. Collaboration and communication with
      doctors about medical patients with elevated EWS was considered to be unrealistic
      due to the high number of patients with these scores. Collaboration with the
      medical emergency team was problematic, since many nurses found the team to have
      negative attitudes. CONCLUSION: EWS reduces complex clinical conditions to a
      single number, with the inherent risk to overlook clinical cues and subtle
      changes in patients' condition. The study showed that identifying and treating
      deteriorating patients is a collaborative task that requires diverse technical
      and non-technical skills for staff to perform optimally.

PMID- 29191160
TI  - The usefulness of the McGrath MAC laryngoscope in comparison with Airwayscope and
      Macintosh laryngoscope during routine nasotracheal intubation: a randomaized
      controlled trial.
AB  - BACKGROUND: McGrath MAC video laryngoscope offers excellent laryngosopic views
      and increases the success rate of orotracheal intubation in some cases. The aim
      of this study was to determine the usefulness of McGrath MAC for routine
      nasotracheal intubation by comparing McGrath MAC with Airway scope and Macintosh
      laryngoscope. METHODS: A total of 60 adult patients with ASA physical status
      class 1 or 2, aged 20-70 years were enrolled in this study. Patients were
      scheduled for elective oral surgery under general anesthesia with nasotracheal
      intubation. Exclusion criteria included lack of consent and expected difficult
      airway. Patients were randomly allocated to three groups: McGrath MAC (n = 20),
      Airway scope (n = 20), and Macintosh laryngoscope (n = 20). After induction,
      nasotracheal intubation was performed by six expert anesthesiologists with more
      than 6 years of experience. RESULTS: There were no significant differences in
      preoperative airway assessment among the three groups. Successful tracheal
      intubation time was 26.8 +/- 5.7 (mean +/- standard deviation) s for McGrath MAC,
      36.4 +/- 11.0 s for Airway scope, and 36.5 +/- 8.9 s for Macintosh laryngoscope
      groups. The time for successful tracheal intubation for McGrath MAC group was
      significantly shorter than that for Airway scope and Macintosh laryngoscope (p <
      0.01). McGrath MAC significantly improved the Cormack Lehane grade for
      nasotracheal intubation compared with Macintosh laryngoscope (p < 0.05).
      CONCLUSION: McGrath MAC significantly facilitates routine nasotracheal intubation
      compared with Airwayscope and Macintosh laryngoscope by shortening the tracheal
      intubation time and improving the Cormack Lehane grade. TRIAL REGISTRATION:
      UMINCTR Registration number UMIN000023506 . Registered 5 Aug 2016.

PMID- 29191161
TI  - Using Mechanical Turk to recruit participants for internet intervention research:
      experience from recruitment for four trials targeting hazardous alcohol
      consumption.
AB  - BACKGROUND: Mechanical Turk (MTurk) is an online portal operated by Amazon where
      'requesters' (individuals or businesses) can submit jobs for 'workers.' MTurk is
      used extensively by academics as a quick and cheap means of collecting
      questionnaire data, including information on alcohol consumption, from a diverse
      sample of participants. We tested the feasibility of recruiting for alcohol
      Internet intervention trials through MTurk. METHODS: Participants, 18 years or
      older, who drank at least weekly were recruited for four intervention trials
      (combined sample size, N = 11,107). The same basic recruitment strategy was
      employed for each trial - invite participants to complete a survey about alcohol
      consumption (less than 15 min in length, US$1.50 payment), identify eligible
      participants who drank in a hazardous fashion, invite those eligible to complete
      a follow-up survey ($10 payment), randomize participants to be sent or not sent
      information to access an online intervention for hazardous alcohol use.
      Procedures where put in place to optimize the chances that participants could
      only complete the baseline survey once. RESULTS: There was a substantially slower
      rate of recruitment by the fourth trial compared to the earlier trials.
      Demographic characteristics also varied across trials (age, sex, employment and
      marital status). Patterns of alcohol consumption, while displaying some
      differences, did not appear to vary in a linear fashion between trials.
      CONCLUSIONS: It is possible to recruit large (but not inexhaustible) numbers of
      people who drink in a hazardous fashion. Issues for online intervention research
      when employing this sample are discussed.

PMID- 29191162
TI  - Severe congenital microcephaly with 16p13.11 microdeletion combined with NDE1
      mutation, a case report and literature review.
AB  - BACKGROUND: Microcephaly is a disorder characterized by severe impairment in
      brain development, reduced brain and head size. Congenital severe microcephaly is
      very rare, and NDE1 deletion and genetic mutations are important contributors.
      CASE PRESENTATION: Single nucleotide polymorphism (SNP) chromosomal microarray
      analysis (CMA) and muation screening of NDE1 gene were performed in an 8-month
      patient with severe congenital microcephaly, and/or his parents. Genetic studies
      found a 16p13.11 deletion containing NDE1 gene, and a novel NDE1 mutation
      c.555_556GC > CT on the non-deleted homolog, inherited from his phenotypically
      normal parents, respectively. The 2 bp nucleotide change results in a missense
      mutation p.K185 N and a nonsense mutation p.Q186X. We also conducted literaturte
      review to compare the clinical phenotypes of our patient to those of cases
      previously reported with NDE1 mutations, and found all patients had mental
      retardation, severe microcephaly, and corpus callosum agenesis. CONCLUSION: This
      is the first Chinese reported with microcephaly caused by NDE1 mutations. NDE1 is
      a critical pathogenetic gene in severe congenital microcephaly. Sequencing NDE1
      and CMA in patients with severe congenital microcephaly may be warranted.

PMID- 29191163
TI  - Antibiotic-resistant bacteria in the guts of insects feeding on plants: prospects
      for discovering plant-derived antibiotics.
AB  - BACKGROUND: Although plants produce many secondary metabolites, currently none of
      these are commercial antibiotics. Insects feeding on specific plants can harbour
      bacterial strains resistant to known antibiotics suggesting that compounds in the
      plant have stimulated resistance development. We sought to determine whether the
      occurrence of antibiotic-resistant bacteria in insect guts was a widespread
      phenomenon, and whether this could be used as a part of a strategy to identify
      antibacterial compounds from plants. RESULTS: Six insect/plant pairs were
      selected and the insect gut bacteria were identified and assessed for antibiotic
      susceptibilities compared with type strains from culture collections. We found
      that the gut strains could be more or less susceptible to antibiotics than the
      type strains, or show no differences. Evidence of antibacterial activity was
      found in the plant extracts from five of the six plants, and, in one case
      Catharanthus roseus (Madagascar Periwinkle), compounds with antibacterial
      activity were identified. CONCLUSION: Bacterial strains isolated from insect guts
      show a range of susceptibilities to antibiotics suggesting a complex interplay
      between species in the insect gut microbiome. Extracts from selected plants can
      show antibacterial activity but it is not easy to isolate and identify the active
      components. We found that vindoline, present in Madagascar Periwinkle extracts,
      possessed moderate antibacterial activity. We suggest that plant-derived
      antibiotics are a realistic possibility given the advances in genomic and
      metabolomic methodologies.

PMID- 29191164
TI  - Weighted likelihood inference of genomic autozygosity patterns in dense genotype
      data.
AB  - BACKGROUND: Genomic regions of autozygosity (ROA) arise when an individual is
      homozygous for haplotypes inherited identical-by-descent from ancestors shared by
      both parents. Over the past decade, they have gained importance for understanding
      evolutionary history and the genetic basis of complex diseases and traits.
      However, methods to infer ROA in dense genotype data have not evolved in step
      with advances in genome technology that now enable us to rapidly create large
      high-resolution genotype datasets, limiting our ability to investigate their
      constituent ROA patterns. METHODS: We report a weighted likelihood approach for
      inferring ROA in dense genotype data that accounts for autocorrelation among
      genotyped positions and the possibilities of unobserved mutation and
      recombination events, and variability in the confidence of individual genotype
      calls in whole genome sequence (WGS) data. RESULTS: Forward-time genetic
      simulations under two demographic scenarios that reflect situations where
      inbreeding and its effect on fitness are of interest suggest this approach is
      better powered than existing state-of-the-art methods to infer ROA at marker
      densities consistent with WGS and popular microarray genotyping platforms used in
      human and non-human studies. Moreover, we present evidence that suggests this
      approach is able to distinguish ROA arising via consanguinity from ROA arising
      via endogamy. Using subsets of The 1000 Genomes Project Phase 3 data we show
      that, relative to WGS, intermediate and long ROA are captured robustly with
      popular microarray platforms, while detection of short ROA is more variable and
      improves with marker density. Worldwide ROA patterns inferred from WGS data are
      found to accord well with those previously reported on the basis of microarray
      genotype data. Finally, we highlight the potential of this approach to detect
      genomic regions enriched for autozygosity signals in one group relative to
      another based upon comparisons of per-individual autozygosity likelihoods instead
      of inferred ROA frequencies. CONCLUSIONS: This weighted likelihood ROA inference
      approach can assist population- and disease-geneticists working with a wide
      variety of data types and species to explore ROA patterns and to identify genomic
      regions with differential ROA signals among groups, thereby advancing our
      understanding of evolutionary history and the role of recessive variation in
      phenotypic variation and disease.

PMID- 29191167
TI  - Using variant databases for variant prioritization and to detect erroneous
      genotype-phenotype associations.
AB  - BACKGROUND: In the search for novel causal mutations, public and/or private
      variant databases are nearly always used to facilitate the search as they result
      in a massive reduction of putative variants in one step. Practically, variant
      filtering is often done by either using all variants from the variant database
      (called the absence-approach, i.e. it is assumed that disease-causing variants do
      not reside in variant databases) or by using the subset of variants with an
      allelic frequency > 1% (called the 1%-approach). We investigate the validity of
      these two approaches in terms of false negatives (the true disease-causing
      variant does not pass all filters) and false positives (a harmless mutation
      passes all filters and is erroneously retained in the list of putative disease
      causing variants) and compare it with an novel approach which we named the
      quantile-based approach. This approach applies variable instead of static
      frequency thresholds and the calculation of these thresholds is based on prior
      knowledge of disease prevalence, inheritance models, database size and database
      characteristics. RESULTS: Based on real-life data, we demonstrate that the
      quantile-based approach outperforms the absence-approach in terms of false
      negatives. At the same time, this quantile-based approach deals more
      appropriately with the variable allele frequencies of disease-causing alleles in
      variant databases relative to the 1%-approach and as such allows a better control
      of the number of false positives. We also introduce an alternative application
      for variant database usage and the quantile-based approach. If disease-causing
      variants in variant databases deviate substantially from theoretical expectancies
      calculated with the quantile-based approach, their association between genotype
      and phenotype had to be reconsidered in 12 out of 13 cases. CONCLUSIONS: We
      developed a novel method and demonstrated that this so-called quantile-based
      approach is a highly suitable method for variant filtering. In addition, the
      quantile-based approach can also be used for variant flagging. For user
      friendliness, lookup tables and easy-to-use R calculators are provided.

PMID- 29191165
TI  - Renal association clinical practice guideline on Anaemia of Chronic Kidney
      Disease.
AB  - Anaemia is a commonly diagnosed complication among patients suffering with
      chronic kidney disease. If left untreated, it may affect patient quality of life.
      There are several causes for anaemia in this patient population. As the kidney
      function deteriorates, together with medications and dietary restrictions,
      patients may develop iron deficiency, resulting in reduction of iron supply to
      the bone marrow (which is the body organ responsible for the production of
      different blood elements). Chronic kidney disease patients may not be able to
      utilise their own body's iron stores effectively and hence, many patients,
      particularly those receiving haemodialysis, may require additional iron
      treatment, usually provided by infusion.With further weakening of kidney
      function, patients with chronic kidney disease may need additional treatment with
      a substance called erythropoietin which drives the bone marrow to produce its own
      blood. This substance, which is naturally produced by the kidneys, becomes
      relatively deficient in patients with chronic kidney disease. Any patients will
      eventually require treatment with erythropoietin or similar products that are
      given by injection.Over the last few years, several iron and erythropoietin
      products have been licensed for treating anaemia in chronic kidney disease
      patients. In addition, several publications discussed the benefits of each
      treatment and possible risks associated with long term treatment. The current
      guidelines provide advice to health care professionals on how to screen chronic
      kidney disease patients for anaemia, which patients to investigate for other
      causes of anaemia, when and how to treat patients with different medications, how
      to ensure safe prescribing of treatment and how to diagnose and manage
      complications associated with anaemia and the drugs used for its treatment.

PMID- 29191168
TI  - Self-reported physical activity correlates in Swedish adults with multiple
      sclerosis: a cross-sectional study.
AB  - BACKGROUND: The benefits of physical activity in persons with Multiple Sclerosis
      (MS) are considerable. Knowledge about factors that correlate to physical
      activity is helpful in order to develop successful strategies to increase
      physical activity in persons with MS. Previous studies have focused on correlates
      to physical activity in MS, however falls self-efficacy, social support and
      enjoyment of physical activity are not much studied, as well as if the correlates
      differ with regard to disease severity. The aim of the study was to examine
      associations between physical activity and age, gender, employment, having
      children living at home, education, disease type, disease severity, fatigue, self
      efficacy for physical activity, falls self-efficacy, social support and enjoyment
      of physical activity in a sample of persons with MS and in subgroups with regard
      to disease severity. METHODS: This is a cross-sectional survey study including
      Swedish community living adults with MS, 287 persons, response rate 58.2%. The
      survey included standardized self-reported scales measuring physical activity,
      disease severity, fatigue, self-efficacy for physical activity, falls self
      efficacy, and social support. Physical activity was measured by the Physical
      Activity Disability Survey - Revised. RESULTS: Multiple regression analyzes
      showed that 59% (F(6,3) = 64.9, p = 0.000) of the variation in physical activity
      was explained by having less severe disease (beta = -0.30), being employed (beta
      = 0.26), having high falls self-efficacy (beta = 0.20), having high self-efficacy
      for physical activity (beta = 0.17), and enjoying physical activity (beta =
      0.11). In persons with moderate/severe MS, self-efficacy for physical activity
      explained physical activity. CONCLUSIONS: Consistent with previous research in
      persons with MS in other countries this study shows that disease severity,
      employment and self-efficacy for physical activity are important for physical
      activity. Additional important factors were falls self-efficacy and enjoyment.
      More research is needed to confirm this and the subgroup differences.

PMID- 29191166
TI  - The insect pathogenic bacterium Xenorhabdus innexi has attenuated virulence in
      multiple insect model hosts yet encodes a potent mosquitocidal toxin.
AB  - BACKGROUND: Xenorhabdus innexi is a bacterial symbiont of Steinernema scapterisci
      nematodes, which is a cricket-specialist parasite and together the nematode and
      bacteria infect and kill crickets. Curiously, X. innexi expresses a potent
      extracellular mosquitocidal toxin activity in culture supernatants. We sequenced
      a draft genome of X. innexi and compared it to the genomes of related pathogens
      to elucidate the nature of specialization. RESULTS: Using green fluorescent
      protein-expressing X. innexi we confirm previous reports using culture-dependent
      techniques that X. innexi colonizes its nematode host at low levels (~3-8 cells
      per nematode), relative to other Xenorhabdus-Steinernema associations. We found
      that compared to the well-characterized entomopathogenic nematode symbiont X.
      nematophila, X. innexi fails to suppress the insect phenoloxidase immune pathway
      and is attenuated for virulence and reproduction in the Lepidoptera Galleria
      mellonella and Manduca sexta, as well as the dipteran Drosophila melanogaster. To
      assess if, compared to other Xenorhabdus spp., X. innexi has a reduced capacity
      to synthesize virulence determinants, we obtained and analyzed a draft genome
      sequence. We found no evidence for several hallmarks of Xenorhabdus spp.
      toxicity, including Tc and Mcf toxins. Similar to other Xenorhabdus genomes, we
      found numerous loci predicted to encode non-ribosomal peptide/polyketide
      synthetases. Anti-SMASH predictions of these loci revealed one, related to the
      fcl locus that encodes fabclavines and zmn locus that encodes zeamines, as a
      likely candidate to encode the X. innexi mosquitocidal toxin biosynthetic
      machinery, which we designated Xlt. In support of this hypothesis, two mutants
      each with an insertion in an Xlt biosynthesis gene cluster lacked the
      mosquitocidal compound based on HPLC/MS analysis and neither produced toxin to
      the levels of the wild type parent. CONCLUSIONS: The X. innexi genome will be a
      valuable resource in identifying loci encoding new metabolites of interest, but
      also in future comparative studies of nematode-bacterial symbiosis and niche
      partitioning among bacterial pathogens.

PMID- 29191169
TI  - Genetic parameters and expected responses to selection for components of feed
      efficiency in a Duroc pig line.
AB  - BACKGROUND: Improving feed efficiency ([Formula: see text]) is a key factor for
      any pig breeding company. Although this can be achieved by selection on an index
      of multi-trait best linear unbiased prediction of breeding values with optimal
      economic weights, considering deviations of feed intake from actual needs
      ([Formula: see text]) should be of value for further research on biological
      aspects of [Formula: see text]. Here, we present a random regression model that
      extends the classical definition of [Formula: see text] by including animal
      specific needs in the model. Using this model, we explore the genetic determinism
      of several [Formula: see text] components: use of feed for growth ([Formula: see
      text]), use of feed for backfat deposition ([Formula: see text]), use of feed for
      maintenance ([Formula: see text]), and unspecific efficiency in the use of feed
      ([Formula: see text]). Expected response to alternative selection indexes
      involving different components is also studied. RESULTS: Based on goodness-of-fit
      to the available feed intake ([Formula: see text]) data, the model that assumes
      individual (genetic and permanent) variation in the use of feed for maintenance,
      [Formula: see text] and [Formula: see text] showed the best performance. Joint
      individual variation in feed allocation to maintenance, growth and backfat
      deposition comprised 37% of the individual variation of [Formula: see text]. The
      estimated heritabilities of [Formula: see text] using the model that accounts for
      animal-specific needs and the traditional [Formula: see text] model were 0.12 and
      0.18, respectively. The estimated heritabilities for the regression coefficients
      were 0.44, 0.39 and 0.55 for [Formula: see text], [Formula: see text] and
      [Formula: see text], respectively. Estimates of genetic correlations of [Formula:
      see text] were positive with amount of feed used for [Formula: see text] and
      [Formula: see text] but negative for [Formula: see text]. Expected response in
      overall efficiency, reducing [Formula: see text] without altering performance,
      was 2.5% higher when the model assumed animal-specific needs than when the
      traditional definition of [Formula: see text] was considered. CONCLUSIONS:
      Expected response in overall efficiency, by reducing [Formula: see text] without
      altering performance, is slightly better with a model that assumes animal
      specific needs instead of batch-specific needs to correct [Formula: see text].
      The relatively small difference between the traditional [Formula: see text] model
      and our model is due to random intercepts (unspecific use of feed) accounting for
      the majority of variability in [Formula: see text]. Overall, a model that
      accounts for animal-specific needs for [Formula: see text], [Formula: see text]
      and [Formula: see text] is statistically superior and allows for the possibility
      to act differentially on [Formula: see text] components.

PMID- 29191170
TI  - The Arabidopsis ELP3/ELO3 and ELP4/ELO1 genes enhance disease resistance in
      Fragaria vesca L.
AB  - BACKGROUND: Plant immune response is associated with a large-scale
      transcriptional reprogramming, which is regulated by numerous transcription
      regulators such as the Elongator complex. Elongator is a multitasking protein
      complex involved in diverse cellular processes, including histone modification,
      DNA methylation, and tRNA modification. In recent years, Elongator is emerging as
      a key regulator of plant immune responses. However, characterization of
      Elongator's function in plant immunity has been conducted only in the model plant
      Arabidopsis thaliana. It is thus unclear whether Elongator's role in plant
      immunity is conserved in higher plants. The objective of this study is to
      characterize transgenic woodland strawberry (Fragaria vesca L.) overexpressing
      the Arabidopsis Elongator (AtELP) genes, AtELP3 and AtELP4, and to determine
      whether F. vesca carries a functional Elongator complex. METHODS: Transgenic F.
      vesca and Arabidopsis plants were produced via Agrobacterium-mediated genetic
      transformation and characterized by morphology, PCR, real-time quantitative PCR,
      and disease resistance test. The Student's t test was used to analyze the data.
      RESULTS: Overexpression of AtELP3 and AtELP4 in F. vesca impacts plant growth and
      development and confers enhanced resistance to anthracnose crown rot, powdery
      mildew, and angular leaf spot, which are caused by the hemibiotrophic fungal
      pathogen Colletotrichum gloeosporioides, the obligate biotrophic fungal pathogen
      Podosphaera aphanis, and the hemibiotrophic bacterial pathogen Xanthomonas
      fragariae, respectively. Moreover, the F. vesca genome encodes all six Elongator
      subunits by single-copy genes with the exception of FvELP4, which is encoded by
      two homologous genes, FvELP4-1 and FvELP4-2. We show that FvELP4-1 complemented
      the Arabidopsis Atelp4/elo1-1 mutant, indicating that FvELP4 is biologically
      functional. CONCLUSIONS: This is the first report on overexpression of Elongator
      genes in plants. Our results indicate that the function of Elongator in plant
      immunity is most likely conserved in F. vesca and suggest that Elongator genes
      may hold potential for helping mitigate disease severity and reduce the use of
      fungicides in strawberry industry.

PMID- 29191171
TI  - Self-assessment of the mental health status in older adults in Poland: a cross
      sectional study.
AB  - BACKGROUND: Demographic aging of society poses numerous challenges, including the
      provision of health care to the elderly population. According to World Health
      Organization data, the most frequent mental disorders in the senior population
      are: dementia, depression, and drug and alcohol addiction. The aim of this study
      was to subjectively assess mental health status (the severity of non-psychotic
      symptoms of mental functions and depressive symptoms) in older adults of
      Bialystok (Poland). METHODS: The study included 300 people - inhabitants of
      Bialystok and its surrounding areas - aged over 60: 100 residents of a nursing
      home, 100 senior students of the University of the Third Age in Bialystok, and
      100 senior students of the University of a Healthy Senior. Two standardized
      psychometric scales were used in the study: the General Health Questionnaire (GHQ
      28) and the Beck Depression Inventory (BDI). RESULTS: The median GHQ total point
      value equaled 26 points, which indicated possible non-psychotic mental disorders.
      The overall BDI score showed that respondents had a subjective feeling of
      depressive symptom intensification at the level of 11 points out of 63 points,
      which indicated minor depressive disorders. Positive and statistically
      significant correlations were observed between suspicion of non-psychotic mental
      disorders and the occurrence of depressive symptoms both without distribution
      into groups and with distribution into sex, group affiliation, and age.
      CONCLUSIONS: Subjective assessment of mental health status in older adults,
      inhabitants of Bialystok, was negative. Social and demographic characteristics
      (sex, group affiliation, age) analyzed in the study, played no significant role
      in the assessment of depressive and non-psychotic mental symptom occurrence.
      Residents of the nursing home were characterized negatively in terms of
      subjective assessment mental health status from the other two study groups.

PMID- 29191172
TI  - MicroRNA profile in HBV-induced infection and hepatocellular carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNAs) exhibit essential regulatory functions related to
      cell growth, apoptosis, development and differentiation. Dysregulated expression
      of miRNAs is associated with a wide variety of human diseases. As such miRNA
      signatures are valuable as biomarkers for disease and for making treatment
      decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular
      carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC.
      METHODS: To determine the miRNAs in HCC occurrence associated with HBV infection,
      we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent
      matched non-HCC tissues from HBV-positive and HBV-negative patients using
      microarray analyses. The microarray result was validated by real-time PCR in 32
      HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate
      target genes of the miRNAs were predicted by miRWalk software. Genes
      simultaneously predicted as targets by two or more miRNAs were subjected to GO
      and KEGG pathway analysis. The miRNA regulatory network analysis was performed
      using the Ingenuity Pathway Analysis (IPA) software. RESULTS: Eight miRNAs (miR
      223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were
      involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p,
      and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p,
      miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered
      in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV
      related HCC miRNAs are involved in the regulation of: transcription, RNA
      polymerase II promoter, phosphorylation of proteins through MAPK signaling
      pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that
      these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly
      influence HCC occurrence and HBV infection. CONCLUSION: Our data indicates that
      the unique 7 miRNAs expression signature could be involved in the development HBV
      related HCC.

PMID- 29191173
TI  - Identifying levels of general distress in first line mental health services: can
      GP- and eHealth clients' scores be meaningfully compared?
AB  - BACKGROUND: The Four-Dimensional Symptom Questionnaire (4DSQ) (Huisarts
      Wetenschap 39: 538-47, 1996) is a self-report questionnaire developed in the
      Netherlands to distinguish non-specific general distress from depression,
      anxiety, and somatization. This questionnaire is often used in different
      populations and settings and there is a paper-and-pencil and computerized
      version. METHODS: We used item response theory to investigate whether the 4DSQ
      measures the same construct (structural equivalence) in the same way (scalar
      equivalence) in two samples comprised of primary mental health care attendees:
      (i) clients who visited their General Practitioner responded to the 4DSQ paper
      and-pencil version, and (ii) eHealth clients responded to the 4DSQ computerized
      version. Specifically, we investigated whether the distress items functioned
      differently in eHealth clients compared to General Practitioners' clients and
      whether these differences lead to substantial differences at scale level.
      RESULTS: Results showed that in general structural equivalence holds for the
      distress scale. This means that the distress scale measures the same construct in
      both General Practitioners' clients and eHealth clients. Furthermore, although
      eHealth clients have higher observed distress scores than General Practitioners'
      clients, application of a multiple group generalized partial credit response
      model suggests that scalar equivalence holds. CONCLUSIONS: The same cutoff scores
      can be used for classifying respondents as having low, moderate and high levels
      of distress in both settings.

PMID- 29191174
TI  - New methods for estimating follow-up rates in cohort studies.
AB  - BACKGROUND: The follow-up rate, a standard index of the completeness of follow
      up, is important for assessing the validity of a cohort study. A common method
      for estimating the follow-up rate, the "Percentage Method", defined as the
      fraction of all enrollees who developed the event of interest or had complete
      follow-up, can severely underestimate the degree of follow-up. Alternatively, the
      median follow-up time does not indicate the completeness of follow-up, and the
      reverse Kaplan-Meier based method and Clark's Completeness Index (CCI) also have
      limitations. METHODS: We propose a new definition for the follow-up rate, the
      Person-Time Follow-up Rate (PTFR), which is the observed person-time divided by
      total person-time assuming no dropouts. The PTFR cannot be calculated directly
      since the event times for dropouts are not observed. Therefore, two estimation
      methods are proposed: a formal person-time method (FPT) in which the expected
      total follow-up time is calculated using the event rate estimated from the
      observed data, and a simplified person-time method (SPT) that avoids estimation
      of the event rate by assigning full follow-up time to all events. Simulations
      were conducted to measure the accuracy of each method, and each method was
      applied to a prostate cancer recurrence study dataset. RESULTS: Simulation
      results showed that the FPT has the highest accuracy overall. In most situations,
      the computationally simpler SPT and CCI methods are only slightly biased. When
      applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and
      SPT showed substantially greater 5-year follow-up than the Percentage Method
      (92%, 92% and 93% vs 68%). CONCLUSIONS: The Person-time methods correct a
      systematic error in the standard Percentage Method for calculating follow-up
      rates. The easy to use SPT and CCI methods can be used in tandem to obtain an
      accurate and tight interval for PTFR. However, the FPT is recommended when event
      rates and dropout rates are high.

PMID- 29191175
TI  - A common base method for analysis of qPCR data and the application of simple
      blocking in qPCR experiments.
AB  - BACKGROUND: qPCR has established itself as the technique of choice for the
      quantification of gene expression. Procedures for conducting qPCR have received
      significant attention; however, more rigorous approaches to the statistical
      analysis of qPCR data are needed. RESULTS: Here we develop a mathematical model,
      termed the Common Base Method, for analysis of qPCR data based on threshold cycle
      values (C q ) and efficiencies of reactions (E). The Common Base Method keeps all
      calculations in the logscale as long as possible by working with log10(E) ? C q ,
      which we call the efficiency-weighted C q value; subsequent statistical analyses
      are then applied in the logscale. We show how efficiency-weighted C q values may
      be analyzed using a simple paired or unpaired experimental design and develop
      blocking methods to help reduce unexplained variation. CONCLUSIONS: The Common
      Base Method has several advantages. It allows for the incorporation of well
      specific efficiencies and multiple reference genes. The method does not
      necessitate the pairing of samples that must be performed using traditional
      analysis methods in order to calculate relative expression ratios. Our method is
      also simple enough to be implemented in any spreadsheet or statistical software
      without additional scripts or proprietary components.

PMID- 29191176
TI  - Mobile electronic versus paper case report forms in clinical trials: a randomized
      controlled trial.
AB  - BACKGROUND: Regulations, study design complexity and amounts of collected and
      shared data in clinical trials render efficient data handling procedures
      inevitable. Recent research suggests that electronic data capture can be key in
      this context but evidence is insufficient. This randomized controlled parallel
      group study tested the hypothesis that time efficiency is superior when
      electronic (eCRF) instead of paper case report forms (pCRF) are used for data
      collection. We additionally investigated predictors of time saving effects and
      data integrity. METHODS: This study was conducted on top of a clinical weight
      loss trial performed at a clinical research facility over six months. All study
      nurses and patients participating in the clinical trial were eligible to
      participate and randomly allocated to enter cross-sectional data obtained during
      routine visits either through pCRF or eCRF. A balanced randomization list was
      generated before enrolment commenced. 90 and 30 records were gathered for the
      time that 27 patients and 2 study nurses required to report 2025 and 2037 field
      values, respectively. The primary hypothesis, that eCRF use is faster than pCRF
      use, was tested by a two-tailed t-test. Analysis of variance and covariance were
      used to evaluate predictors of entry performance. Data integrity was evaluated by
      descriptive statistics. RESULTS: All randomized patients were included in the
      study (eCRF group n = 13, pCRF group n = 14). eCRF, as compared to pCRF, data
      collection was associated with significant time savings  across all conditions
      (8.29 +/- 5.15 min vs. 10.54 +/- 6.98 min, p = .047). This effect was not defined
      by participant type, i.e. patients or study nurses (F(1,112) = .15, p = .699),
      CRF length (F(2,112) = .49, p = .609) or patient age (Beta = .09, p = .534).
      Additional 5.16 +/- 2.83 min per CRF were saved with eCRFs due to data
      transcription redundancy when patients answered questionnaires directly in eCRFs.
      Data integrity was superior in the eCRF condition (0 versus 3 data entry errors).
      CONCLUSIONS: This is the first study to prove in direct comparison that using
      eCRFs instead of pCRFs increases time efficiency of data collection in clinical
      trials, irrespective of item quantity or patient age, and improves data quality.
      TRIAL REGISTRATION: Clinical Trials NCT02649907 .

PMID- 29191177
TI  - Performance comparison of first-order conditional estimation with interaction and
      Bayesian estimation methods for estimating the population parameters and its
      distribution from data sets with a low number of subjects.
AB  - BACKGROUND: Exploratory preclinical, as well as clinical trials, may involve a
      small number of patients, making it difficult to calculate and analyze the
      pharmacokinetic (PK) parameters, especially if the PK parameters show very high
      inter-individual variability (IIV). In this study, the performance of a classical
      first-order conditional estimation with interaction (FOCE-I) and expectation
      maximization (EM)-based Markov chain Monte Carlo Bayesian (BAYES) estimation
      methods were compared for estimating the population parameters and its
      distribution from data sets having a low number of subjects. METHODS: In this
      study, 100 data sets were simulated with eight sampling points for each subject
      and with six different levels of IIV (5%, 10%, 20%, 30%, 50%, and 80%) in their
      PK parameter distribution. A stochastic simulation and estimation (SSE) study was
      performed to simultaneously simulate data sets and estimate the parameters using
      four different methods: FOCE-I only, BAYES(C) (FOCE-I and BAYES composite
      method), BAYES(F) (BAYES with all true initial parameters and fixed omega 2 ),
      and BAYES only. Relative root mean squared error (rRMSE) and relative estimation
      error (REE) were used to analyze the differences between true and estimated
      values. A case study was performed with a clinical data of theophylline available
      in NONMEM distribution media. NONMEM software assisted by Pirana, PsN, and Xpose
      was used to estimate population PK parameters, and R program was used to analyze
      and plot the results. RESULTS: The rRMSE and REE values of all parameter (fixed
      effect and random effect) estimates showed that all four methods performed
      equally at the lower IIV levels, while the FOCE-I method performed better than
      other EM-based methods at higher IIV levels (greater than 30%). In general,
      estimates of random-effect parameters showed significant bias and imprecision,
      irrespective of the estimation method used and the level of IIV. Similar
      performance of the estimation methods was observed with theophylline dataset.
      CONCLUSIONS: The classical FOCE-I method appeared to estimate the PK parameters
      more reliably than the BAYES method when using a simple model and data containing
      only a few subjects. EM-based estimation methods can be considered for adapting
      to the specific needs of a modeling project at later steps of modeling.

PMID- 29191178
TI  - A fast indirect method to compute functions of genomic relationships concerning
      genotyped and ungenotyped individuals, for diversity management.
AB  - BACKGROUND: Pedigree-based management of genetic diversity in populations, e.g.,
      using optimal contributions, involves computation of the [Formula: see text] type
      yielding elements (relationships) or functions (usually averages) of relationship
      matrices. For pedigree-based relationships [Formula: see text], a very efficient
      method exists. When all the individuals of interest are genotyped, genomic
      management can be addressed using the genomic relationship matrix [Formula: see
      text]; however, to date, the computational problem of efficiently computing
      [Formula: see text] has not been well studied. When some individuals of interest
      are not genotyped, genomic management should consider the relationship matrix
      [Formula: see text] that combines genotyped and ungenotyped individuals; however,
      direct computation of [Formula: see text] is computationally very demanding,
      because construction of a possibly huge matrix is required. Our work presents
      efficient ways of computing [Formula: see text] and [Formula: see text], with
      applications on real data from dairy sheep and dairy goat breeding schemes.
      RESULTS: For genomic relationships, an efficient indirect computation with
      quadratic instead of cubic cost is [Formula: see text], where Z is a matrix
      relating animals to genotypes. For the relationship matrix [Formula: see text],
      we propose an indirect method based on the difference between vectors [Formula:
      see text], which involves computation of [Formula: see text] and of products such
      as [Formula: see text] and [Formula: see text], where [Formula: see text] is a
      working vector derived from [Formula: see text]. The latter computation is the
      most demanding but can be done using sparse Cholesky decompositions of matrix
      [Formula: see text], which allows handling very large genomic and pedigree data
      files. Studies based on simulations reported in the literature show that the
      trends of average relationships in [Formula: see text] and [Formula: see text]
      differ as genomic selection proceeds. When selection is based on genomic
      relationships but management is based on pedigree data, the true genetic
      diversity is overestimated. However, our tests on real data from sheep and goat
      obtained before genomic selection started do not show this. CONCLUSIONS: We
      present efficient methods to compute elements and statistics of the genomic
      relationships [Formula: see text] and of matrix [Formula: see text] that combines
      ungenotyped and genotyped individuals. These methods should be useful to monitor
      and handle genomic diversity.

PMID- 29191179
TI  - Decontaminating eukaryotic genome assemblies with machine learning.
AB  - BACKGROUND: High-throughput sequencing has made it theoretically possible to
      obtain high-quality de novo assembled genome sequences but in practice DNA
      extracts are often contaminated with sequences from other organisms. Currently,
      there are few existing methods for rigorously decontaminating eukaryotic
      assemblies. Those that do exist filter sequences based on nucleotide similarity
      to contaminants and risk eliminating sequences from the target organism. RESULTS:
      We introduce a novel application of an established machine learning method, a
      decision tree, that can rigorously classify sequences. The major strength of the
      decision tree is that it can take any measured feature as input and does not
      require a priori identification of significant descriptors. We use the decision
      tree to classify de novo assembled sequences and compare the method to published
      protocols. CONCLUSIONS: A decision tree performs better than existing methods
      when classifying sequences in eukaryotic de novo assemblies. It is efficient,
      readily implemented, and accurately identifies target and contaminant sequences.
      Importantly, a decision tree can be used to classify sequences according to
      measured descriptors and has potentially many uses in distilling biological
      datasets.

PMID- 29191180
TI  - White, affluent, educated parents are least likely to choose HPV vaccination for
      their children: a cross-sectional study of the National Immunization Study -
      teen.
AB  - BACKGROUND: Human Papillomavirus (HPV) vaccination coverage is below national
      goals in the United States. Research is needed to inform strategically designed
      interventions that target sociodemographic groups with underutilization of HPV
      vaccination. METHODS: Secondary data analysis of the National Immunization Survey
      Teen 2013 measured association of sociodemographic factors (e.g., ethnicity/race,
      insurance) with HPV vaccination among females and males ages 13-17 (N = 18,959).
      Chi-square and multivariable Poisson regressions were conducted using survey
      weighted statistics. RESULTS: Having a mother >=35 years, a mother with some
      college, being of "Other" ethnicity/race, and having no providers who order
      vaccines from health departments was negatively associated with females
      initiating HPV vaccination. Having a mother with some college, being of Non
      Hispanic White or "Other" ethnicity/race, and having some or no providers who
      order vaccines from health departments was negatively associated with males
      initiating HPV vaccination. These same factors were negatively associated with
      males completing HPV vaccination with the exception of "Other" ethnicity/race. In
      contrast, having an unmarried mother, being ages 15-17, having a hospital based
      provider, and receiving other adolescent vaccinations were positively associated
      with females initiating and completing HPV vaccination. Having an unmarried
      mother, health insurance that is not employer or union sponsored, and influenza
      and meningitis vaccinations was positively associated with male's initiating HPV
      vaccination. For males, being 15 or 17 years old and having other adolescent
      vaccinations was positively associated with vaccine completion. All findings p <=
      0.05. CONCLUSIONS: Future HPV vaccination interventions may benefit from
      targeting certain sociodemographic groups that were negatively associated with
      HPV vaccination in this study.

PMID- 29191181
TI  - Immunohistochemistry defined subtypes of breast cancer in 678 Sudanese and
      Eritrean women; hospitals based case series.
AB  - BACKGROUND: Breast cancer is the most common malignancy accounting for 25% of all
      cancers in females. In Africa, breast cancer prevalence and mortality are
      steadily increasing. Knowledge of hormone receptors and human epidermal growth
      factor receptor-2 (HER-2) expressions are vital for breast cancer management
      plans and decision making. There is wide regional variation in the proportion of
      these biomarkers, especially in African countries. Hormone receptors positivity
      in indigenous African and African American women is considered to be low and
      triple negative breast cancer is a dominant phenotype. There is paucity of data
      regarding hormone receptors (ER and PR) and HER2 expressions in North-eastern
      Africa (Eritrea and Sudan). The purpose of this study was to evaluate the
      expression of ER, PR and HER2 in Eritrean and Sudanese case series and correlate
      these biomarkers with the clinicopathological profile. METHOD: Clinicopathologic
      data of patients were collected from clinical records. Immunohistochemistry
      biomarkers (ER, PR, and HER2) were assessed in consecutive female patients who
      had been diagnosed with invasive breast cancer from 2011 to 2015 in Gezira
      University Pathology Laboratory, the Sudan and National Health laboratory,
      Asmara, Eritrea. RESULTS: There were 678 cases involved in this study. The mean
      age was 48.8 years with +/-0.53 standard error of the mean. Two-thirds of the
      case were <=50 years. Invasive ductal carcinoma, no special type was the most
      dominant histologic type (86%) in both study groups. The majority of cases (70%)
      had tumour stage pT2 and pT3 and about 50% had lymph node involvement. Less than
      5% of the cases had well-differentiated tumours. The ER, PR and HER2 positive
      rates were 45%, 32%, and 29%, respectively. The proportion of luminal-A like,
      luminal-B like, HER2 enriched and TNBC were 37%, 13%, 16% and 34%, respectively.
      Fisher extract analysis showed age (p = .015), tumour size (p = .041), and
      histologic grade (p = .000) were significantly associated with intrinsic
      subtypes. Furthermore, Logistic regression analysis stratified by origin, age,
      tumour size, lymph-node metastasis and grade indicated that younger women age
      (<=50 years) and grade III tumours were more likely to be diagnosed with ER
      negative breast cancer. CONCLUSION: Most of Sudanese and Eritrean women were
      diagnosed at younger age and with unfavourable prognostic clinicopathologic
      prognostic markers. TNBC is more frequent in this cohort study; patients with
      grade III tumours and young age are more likely to be hormone receptors negative.
      Therefore, routine determination of hormone receptors is warranted for
      appropriate targeted therapy.

PMID- 29191182
TI  - What systemic factors contribute to collaboration between primary care and public
      health sectors? An interpretive descriptive study.
AB  - BACKGROUND: Purposefully building stronger collaborations between primary care
      (PC) and public health (PH) is one approach to strengthening primary health care.
      The purpose of this paper is to report: 1) what systemic factors influence
      collaborations between PC and PH; and 2) how systemic factors interact and could
      influence collaboration. METHODS: This interpretive descriptive study used
      purposive and snowball sampling to recruit and conduct interviews with PC and PH
      key informants in British Columbia (n = 20), Ontario (n = 19), and Nova Scotia (n
      = 21), Canada. Other participants (n = 14) were knowledgeable about
      collaborations and were located in various Canadian provinces or working at a
      national level. Data were organized into codes and thematic analysis was
      completed using NVivo. The frequency of "sources" (individual transcripts),
      "references" (quotes), and matrix queries were used to identify potential
      relationships between factors. RESULTS: We conducted a total of 70 in-depth
      interviews with 74 participants working in either PC (n = 33) or PH (n = 32),
      both PC and PH (n = 7), or neither sector (n = 2). Participant roles included
      direct service providers (n = 17), senior program managers (n = 14), executive
      officers (n = 11), and middle managers (n = 10). Seven systemic factors for
      collaboration were identified: 1) health service structures that promote
      collaboration; 2) funding models and financial incentives supporting
      collaboration; 3) governmental and regulatory policies and mandates for
      collaboration; 4) power relations; 5) harmonized information and communication
      infrastructure; 6) targeted professional education; and 7) formal systems leaders
      as collaborative champions. CONCLUSIONS: Most themes were discussed with equal
      frequency between PC and PH. An assessment of the system level context (i.e.,
      provincial and regional organization and funding of PC and PH, history of
      government in successful implementation of health care reform, etc) along with
      these seven system level factors could assist other jurisdictions in moving
      towards increased PC and PH collaboration. There was some variation in the
      importance of the themes across provinces. British Columbia participants more
      frequently discussed system structures that could promote collaboration, power
      relations, harmonized information and communication structures, formal systems
      leaders as collaboration champions and targeted professional education. Ontario
      participants most frequently discussed governmental and regulatory policies and
      mandates for collaboration.

PMID- 29191183
TI  - An economic model of advance care planning in Australia: a cost-effective way to
      respect patient choice.
AB  - BACKGROUND: Advance care planning (ACP) is a process of planning for future
      health and personal care. A person's values and preferences are made known so
      that they can guide decision making at a future time when that person cannot make
      or communicate his or her decisions. This is particularly relevant for people
      with dementia because their ability to make decisions progressively deteriorates
      over time. This study aims to evaluate the cost-effectiveness of delivering a
      nationwide ACP program within the Australian primary care setting. METHODS: A
      decision analytic model was developed to identify the costs and outcomes of an
      ACP program for people aged 65+ years who were at risk of developing dementia.
      Inputs for the model was sourced and estimated from the literature. The
      reliability of the results was thoroughly tested in sensitivity analyses.
      RESULTS: The results showed that, compared to usual care, a nationwide ACP
      program for people aged 65+ years who were at risk of dementia would be cost
      effective. However, the results only hold if ACP completion is higher than 50%
      and adherence to ACP wishes is above 75%. CONCLUSIONS: A nationwide ACP program
      in the primary care setting is a cost-effective or cost-saving intervention
      compared to usual care in a population at-risk of developing dementia. Cost
      savings are generated from providing treatment and care that is consistent with
      patient preferences, resulting in fewer hospitalisations and less-intensive care
      at end-of-life.

PMID- 29191184
TI  - Accessibility of general and specialized obstetric care providers in Germany and
      England: an analysis of location and neonatal outcome.
AB  - BACKGROUND: Health care accessibility is known to differ geographically. With
      this study we focused on analysing accessibility of general and specialized
      obstetric units in England and Germany with regard to urbanity, area deprivation
      and neonatal outcome using routine data. METHODS: We used a floating catchment
      area method to measure obstetric care accessibility, the degree of urbanization
      (DEGURBA) to measure urbanity and the index of multiple deprivation to measure
      area deprivation. RESULTS: Accessibility of general obstetric units was
      significantly higher in Germany compared to England (accessibility index of 16.2
      vs. 11.6; p < 0.001), whereas accessibility of specialized obstetric units was
      higher in England (accessibility index for highest level of care of 0.235 vs.
      0.002; p < 0.001). We further demonstrated higher obstetric accessibility for
      people living in less deprived areas in Germany (r = - 0.31; p < 0.001) whereas
      no correlation was present in England. There were also urban-rural disparities
      present, with higher accessibility in urban areas in both countries (r = 0.37
      0.39; p < 0.001). The analysis did not show that accessibility affected neonatal
      outcomes. Finally, our computer generated model for obstetric care provider
      demand in terms of birth counts showed a very strong correlation with actual
      birth counts at obstetric units (r = 0.91-0.95; p < 0.001). CONCLUSION: In
      Germany the focus of obstetric care seemed to be put on general obstetric units
      leading to higher accessibility compared to England. Regarding specialized
      obstetric care the focus in Germany was put on high level units whereas in
      England obstetric care seems to be more balanced between the different levels of
      care with larger units on average leading to higher accessibility.

PMID- 29191186
TI  - Roles and responsibilities of clinical ethics committees in priority setting.
AB  - BACKGROUND: Fair prioritization of healthcare resources has been on the agenda
      for decades, but resource allocation dilemmas in clinical practice remain
      challenging. Can clinical ethics committees (CECs) be of help? The aim of the
      study was to explore whether and how CECs handle priority setting dilemmas and
      contribute to raising awareness of fairness concerns. METHOD: Descriptions of
      activities involving priority setting in annual reports from Norwegian CECs (2003
      2015) were studied and categorized through qualitative content analysis. RESULTS:
      Three hundred thirty-nine reports from 38 CECs were studied. We found 78
      activities where resource use or priority setting were explicitly highlighted as
      main topics. Of these, 29 were seminars or other educational activities, 21 were
      deliberations on individual patient cases, whereas 28 were discussions of
      principled or general cases. Individual patient cases concerned various
      distributional dilemmas where values were at stake. Six main topics and seven
      roles for the CEC were identified. CECs handle issues concerning the introduction
      of new costly drugs, extraordinarily costly established treatment, the
      application of priority setting criteria, resource use for vulnerable groups,
      resource constraints compromising practice, and futility of care. The CEC can act
      as an analyst, advisor, moderator, disseminator, facilitator, watch dog, and
      guardian of values and laws. DISCUSSION: In order to fulfil their
      responsibilities in handling priority setting cases, CECs need knowledge of both
      the ethics and the institutionalized systems of priority setting. There is
      potential for developing this aspect of the CECs' work further. CONCLUSIONS: The
      Norwegian CECs are involved in priority setting decisions where they can play
      multiple constructive roles. In particular, they advise and raise awareness of
      ethical aspects in resource allocations; bridge clinical practice with higher
      level decisions; and promote fair resource allocation and stakeholder rights and
      interests.

PMID- 29191185
TI  - Compassionate collaborative care: an integrative review of quality indicators in
      end-of-life care.
AB  - BACKGROUND: Compassion and collaborative practice are individually associated
      with high quality healthcare. When combined in a compassionate collaborative care
      (CCC) practice framework, they are reported to improve health, strengthen care
      provision, and control health costs. Little is known about how to integrate and
      measure CCC, yet it is fundamentally applied in palliative and end-of-life care
      settings. This study aimed to identify quality indicators of CCC by
      systematically reviewing and synthesizing the current state of the palliative and
      end-of-life care literature. METHODS: An integrative review of the palliative and
      end-of-life care literature was conducted using Whittemore and Knafl's method.
      Donabedian's healthcare quality framework was applied in the data analysis phase
      to organize and display the data. The analysis involved an iterative process that
      applied a constant comparative method. RESULTS: The final literature sample
      included 25 articles. Patient and family-centered care emerged as a primary
      structure for CCC, with overarching values including empathy, sharing, respect,
      and partnership. The analysis revealed communication, shared decision-making, and
      goal setting as overarching processes for achieving CCC at end-of-life. Patient
      and family satisfaction, enhanced teamwork, decreased staff burnout, and
      organizational satisfaction are exemplars of outcomes that suggest high quality
      CCC. Specific quality indicators at the individual, team and organizational
      levels are reported with supporting exemplar data. CONCLUSIONS: CCC is
      inextricably linked to the inherent values, needs and expectations of patients,
      families and healthcare providers. Compassion and collaboration must be enacted
      and harmonized to fully operationalize and sustain patient and family-centered
      care in palliative and end-of-life practice settings. Towards that direction, the
      quality indicators that emerged from this integrative review provide a two-fold
      application in palliative and end-of-life care. First, to evaluate the existing
      structures, processes, and outcomes at the patient-family, provider, team, and
      organizational levels. Second, to guide the planning and implementation of team
      and organizational changes that improve the quality delivery of CCC.

PMID- 29191187
TI  - Clinical value of a prophylactic minitracheostomy after esophagectomy: analysis
      in patients at high risk for postoperative pulmonary complications.
AB  - BACKGROUND: The aim of this study is to evaluate the clinical value of a
      prophylactic minitracheostomy (PMT) in patients undergoing an esophagectomy for
      esophageal cancer and to clarify the indications for a PMT. METHODS: Ninety-four
      patients who underwent right transthoracic esophagectomy for esophageal cancer
      between January 2009 and December 2013 were studied. Short surgical outcomes were
      retrospectively compared between 30 patients at high risk for postoperative
      pulmonary complications who underwent a PMT (PMT group) and 64 patients at
      standard risk without a PMT (non-PMT group). Furthermore, 12 patients who
      required a delayed minitracheostomy (DMT) due to postoperative sputum retention
      were reviewed in detail, and risk factors related to a DMT were also analyzed to
      assess the indications for a PMT. RESULTS: Preoperative pulmonary function was
      lower in the PMT group than in the non-PMT group: FEV1.0 (2.41 vs. 2.68 L, p =
      0.035), and the proportion of patients with FEV1.0% <60 (13.3% vs. 0%, p =
      0.009). No between-group differences were observed in the proportion of patients
      who suffered from postoperative pneumonia, atelectasis, or re-intubation due to
      respiratory failure. Of the 12 patients with a DMT, 11 developed postoperative
      pneumonia, and three required re-intubation due to severe pneumonia. Multivariate
      analysis revealed FEV1.0% <70% and vocal cord palsy were independent risk factors
      related to a DMT. CONCLUSION: A PMT for high-risk patients may prevent an
      increase in the incidence of postoperative pneumonia and re-intubation. The PMT
      indications should be expanded for patients with vocal cord palsy or mild
      obstructive respiratory disturbances.

PMID- 29191188
TI  - Construct validation and correlates of preoperative expectations of postsurgical
      recovery in persons undergoing knee replacement: baseline findings from a
      randomized clinical trial.
AB  - BACKGROUND: A patient's recovery expectations prior to knee arthroplasty
      influence postsurgical outcome and satisfaction but a unidimensional measure of
      expectation has not been reported in the literature. Our primary purpose was to
      determine the extent to which a patient expectations scale reflects a
      unidimensional construct. Our second purpose was to identify pre-operative
      variables associated with patients' expectations. We hypothesized that previously
      identified predictors of the latent expectation scale score would be associated
      with expectations and that previously unexplored variables of pain
      catastrophizing, depressive and anxiety symptoms, self-efficacy and number of
      painful body regions would also associate with pre-operative expectations.
      METHODS: Our randomized clinical trial had 384 patients assessed prior to knee
      replacement surgery. The expectations scale along with several predictor
      variables including WOMAC, psychological distress, and sociodemographic variables
      were obtained. Confirmatory factor analysis tested the unidimensionality of the
      measure and structural equation modeling identified predictors of the latent
      expectations measure. RESULTS: The expectations scale was found to be
      unidimensional with superior model fit (chi2 = 1.481; df = 2; p = 0.224; RMSEA =
      0.035; 90% CI = [0-0.146]; CFI = 0.999; TLI = 0.993). The only variable
      significantly associated with expectations in the multivariate model was self
      efficacy. CONCLUSIONS: The expectations scale used in our study demonstrated
      unidimensionality and has strong potential for clinical application. Poor self
      efficacy is a potential target for intervention given its independent association
      with expectation. Addressing expectations directly and indirectly through self
      efficacy assessment may assist in better aligning patient's expectations with
      likely outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT01620983 .

PMID- 29191189
TI  - Fostering clinical reasoning in physiotherapy: comparing the effects of concept
      map study and concept map completion after example study in novice and advanced
      learners.
AB  - BACKGROUND: Health profession learners can foster clinical reasoning by studying
      worked examples presenting fully worked out solutions to a clinical problem. It
      is possible to improve the learning effect of these worked examples by combining
      them with other learning activities based on concept maps. This study
      investigated which combinaison of activities, worked examples study with concept
      map completion or worked examples study with concept map study, fosters more
      meaningful learning of intervention knowledge in physiotherapy students.
      Moreover, this study compared the learning effects of these learning activity
      combinations between novice and advanced learners. METHODS: Sixty-one second-year
      physiotherapy students participated in the study which included a pre-test phase,
      a 130-min guided-learning phase and a four-week self-study phase. During the
      guided and self-study learning sessions, participants had to study three written
      worked examples presenting the clinical reasoning for selecting
      electrotherapeutic currents to treat patients with motor deficits. After each
      example, participants engaged in either concept map completion or concept map
      study depending on which learning condition they were randomly allocated to.
      Students participated in an immediate post-test at the end of the guided-learning
      phase and a delayed post-test at the end of the self-study phase. Post-tests
      assessed the understanding of principles governing the domain of knowledge to be
      learned (conceptual knowledge) and the ability to solve new problems that have
      similar (i.e., near transfer) or different (i.e., far transfer) solution
      rationales as problems previously studied in the examples. RESULTS: Learners
      engaged in concept map completion outperformed those engaged in concept map study
      on near transfer (p = .010) and far transfer (p < .001) performance. There was a
      significant interaction effect of learners' prior ability and learning condition
      on conceptual knowledge but not on near and far transfer performance.
      CONCLUSIONS: Worked examples study combined with concept map completion led to
      greater transfer performance than worked examples study combined with concept map
      study for both novice and advanced learners. Concept map completion might give
      learners better insight into what they have and have not yet learned, allowing
      them to focus on those aspects during subsequent example study.

PMID- 29191190
TI  - The effects of freeze-dried Ganoderma lucidum mycelia on a recurrent oral
      ulceration rat model.
AB  - BACKGROUND: Conventional scientific studies had supported the use of
      polysaccharides and beta-glucans from a number of fungi, including Ganoderma
      lucidum for the treatment of recurrent oral ulceration (ROU). Our aim of the
      present study was to evaluate whether freeze-dried powder from G. lucidum mycelia
      (FDPGLM) prevents ROU in rats. METHODS: A Sprague-Dawley (SD) rat model with ROU
      was established by autoantigen injection. The ROU rats were treated with three
      different dosages of FDPGLM and prednisone acetate (PA), and their effects were
      evaluated according to the clinical therapeutic evaluation indices of ROU.
      RESULTS: High-dose FDPGLM induced significantly prolonged total intervals and a
      reduction in the number of ulcers and ulcer areas, thereby indicating that the
      treatment was effective in preventing ROU. Enzyme-linked immunosorbent assay
      (ELISA) showed that high-dose FDPGLM significantly enhanced the serum
      transforming growth factor-beta1 (TGF-beta1) levels, whereas reduced those of
      interleukin-6 (IL-6) and interleukin-17 (IL-17). Flow cytometry (FCM) showed that
      the proportion of CD4+ CD25+ Foxp3+ (forkhead box P3) regulatory T cells (Tregs)
      significantly increased by 1.5-fold in the high-dose FDPGLM group compared to
      that in the rat model group (P < 0.01). The application of middle- and high-dose
      FDPGLM also resulted in the upregulation of Foxp3 and downregulation of retinoid
      related orphan receptor gamma t(RORgammat) mRNA. CONCLUSION: High-dose FDPGLM
      possibly plays a role in ROU by promoting CD4+ CD25+ Foxp3+ Treg and inhibiting T
      helper cell 17 differentiation. This study also shows that FDPGLM may be
      potentially used as a complementary and alternative medicine treatment scheme for
      ROU.

PMID- 29191192
TI  - Anticancer activities of ethanol extract from the Antarctic freshwater microalga,
      Botryidiopsidaceae sp.
AB  - BACKGROUND: Cancer is a leading cause of human death around the world and occurs
      through the highly complex coordination of multiple cellular pathways. Recent
      studies have revealed that microalgal extracts exhibit considerable
      pharmaceutical activities, including those against various cancer cells. Thus,
      microalgae are promising candidates as novel cancer therapeutic drugs. In this
      study, we evaluated the biological functions of the ethanolic extract of the
      Antarctic freshwater microalga, Bo tryidiopsidaceae sp., such as its antioxidant,
      anti-proliferative, apoptotic and anti-invasive properties. METHODS: To estimate
      antioxidant capacity of ethanol extract of Bo tryidiopsidaceae sp. (ETBO), free
      radical 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and 1,1
      diphenyl-2-picrylhydrazyl (DPPH) assays were used. The anti-proliferative
      activity of ETBO was assessed in several cancer cell lines (A375, Hs578T and
      HeLa) and non-tumorigenic keratinocyte cells (HaCaT), using MTT assay. In
      addition, Annexin V binding was performed to detect ETBO-induced apoptotic cells,
      and the expression levels of apoptosis-regulating proteins, caspase-3, p53, and
      Bcl-2, were determined by western blot. Boyden chamber assays were used to
      determine anti-migratory and anti-invasive properties of ETBO. RESULTS: ETBO
      exhibited antioxidant activity and concentration-dependent anticancer activities,
      such as anti-proliferation and pro-apoptotic activities against cancer cells.
      Furthermore, the expression of the apoptosis-inducing proteins, p53 and caspase
      3, significantly increased in response to ETBO, whereas the expression of the
      anti-apoptotic protein, Bcl-2, decreased. These data imply that ETBO induces
      apoptosis by caspase activation through the modulation of pro-apoptotic and anti
      apoptotic gene, p53 and Bcl-2, respectively. In addition, ETBO significantly
      inhibited migration and invasion of cervical cancer cells in a concentration
      dependent manner. CONCLUSION: In this study, ETBO exhibited considerable
      anticancer activities, such as inhibition of proliferation, invasion, and
      migration, as well as induction of apoptosis. These data suggest that ETBO is a
      promising therapeutic agent in cancer therapy and drug discovery.

PMID- 29191191
TI  - Asymptomatic infections with highly polymorphic Chlamydia suis are ubiquitous in
      pigs.
AB  - BACKGROUND: Chlamydia suis is an important, globally distributed, highly
      prevalent and diverse obligate intracellular pathogen infecting pigs. To
      investigate the prevalence and genetic diversity of C. suis in China, 2,137
      nasal, conjunctival, and rectal swabs as well as whole blood and lung samples of
      pigs were collected in 19 regions from ten provinces of China in this study.
      RESULTS: We report an overall positivity of 62.4% (1,334/2,137) of C. suis
      following screening by Chlamydia spp. 23S rRNA-based FRET-PCR and high-resolution
      melting curve analysis and confirmatory sequencing. For C. suis-positive samples,
      33.3 % of whole blood and 62.5% of rectal swabs were found to be positive for the
      C. suis tetR(C) gene, while 13.3% of whole blood and 87.0% of rectal swabs were
      positive for the C. suis tet(C) gene. Phylogenetic comparison of partial C. suis
      ompA gene sequences revealed significant genetic diversity in the C. suis
      strains. This genetic diversity was confirmed by C. suis-specific multilocus
      sequence typing (MLST), which identified 26 novel sequence types among 27
      examined strains. Tanglegrams based on MLST and ompA sequences provided evidence
      of C. suis recombination amongst the strains analyzed. CONCLUSIONS: Genetically
      highly diverse C. suis strains are exceedingly prevalent in pigs. As it stands,
      the potential pathogenic effect of C. suis on pig health and production of C.
      suis remains unclear and will be the subject of further investigations. Further
      study is also required to address the transmission of C. suis between pigs and
      the risk of 'spill-over' and 'spill-back' of infections to wild animals and
      humans.

PMID- 29191194
TI  - Integrating herbal medicine into mainstream healthcare in Ghana: clients'
      acceptability, perceptions and disclosure of use.
AB  - BACKGROUND: Although there are current efforts to integrate herbal medicine (HM)
      into mainstream healthcare in Ghana, there is paucity of empirical evidence on
      the acceptability and concurrent use of HM, in the formal health facilities in
      Ghana. This study sought to determine client perception, disclosure and
      acceptability of integrating herbal medicine in mainstream healthcare in Kumasi,
      Ghana. METHODS: A cross-sectional study was conducted from May to August, 2015.
      Five hundred patients presenting at the outpatient departments of Kumasi South,
      Suntreso and Tafo Government Hospitals in Kumasi were randomly selected.
      Interviews were conducted with the use of structured questionnaires. A logistic
      regression analysis, using backward selection, was conducted to determine the
      influence of socio-demographic and facility related factors on the odds of using
      HM at the facility. All statistical tests were two-sided and considered
      significant at a p-value of <0.05. RESULTS: Majority of the study respondents
      were females (64.8%) and the median age was 36 years. Less than half, 42.2%, of
      the respondents utilized HM services when they visited the health facility.
      Reasons for using HM at the facility level included 'being effective' (24.4%),
      'easy to access' (25.3%) and 'being comparatively cheaper' (16%). About 86% never
      disclosed previous use of HM to their health care providers. Socio-economic
      status and perception of service provision influenced use of herbal medicines.
      Respondents who rated themselves wealthy had increased odds of using herbal
      medicines at the health facility as compared to those who rated themselves poor
      (OR = 4.9; 95%CI = 1.6-15.3). CONCLUSION: This study shows that integration of
      herbal medicine is feasible and herbal medicines may be generally accepted as a
      formal source of healthcare in Ghana. The results of this study might serve as a
      basis for improvement and upscale of the herbal medicine integration programme in
      Ghana.

PMID- 29191193
TI  - Adequacy of control of cardiovascular risk factors in ambulatory patients with
      type 2 diabetes attending diabetes out-patients clinic at a county hospital,
      Kenya.
AB  - BACKGROUND: Type 2 diabetes is associated with substantial cardiovascular
      morbidity and mortality arising from the high prevalence of cardiovascular risk
      factors such as hypertension, dyslipidaemia, obesity, poor glycaemic control and
      albuminuria. Adequacy of control of these risk factors determines the frequency
      and outcome of cardiovascular events in the patients. Current clinical practice
      guidelines emphasize primary prevention of cardiovascular disease in type 2
      diabetes. There is scarce data from the developing countries, Kenya included, on
      clinical care of patients with type 2 diabetes in the regions that are far away
      from tertiary health facilities. So we determined the adequacy of control of the
      modifiable risk factors: glycaemic control, hypertension, dyslipidemia, obesity
      and albuminuria in the study patients from rural and peri-urban dwelling.
      METHODS: This was a cross-sectional study on 385 randomly selected ambulatory
      patients with type 2 diabetes without overt complications. They were on follow up
      for at least 6 months at the Out-patient diabetes clinic of Nyeri County
      Hospital, a public health facility located in the central region of Kenya.
      RESULTS: Females were 65.5%. The study subjects had a mean duration of diabetes
      of 9.4 years, IQR of 3.0-14 years. Their mean age was 63.3 years, IQR of 56-71
      years. Only 20.3% of our subjects had simultaneous optimal control of the three
      (3) main cardiovascular risk factors of hypertension, high LDL-C and
      hyperglycaemia at the time of the study. The prevalence of cardiovascular risk
      factors were as follows: HbA1c above 7% was 60.5% (95% CI, 55.6-65.5),
      hypertension, 49.6% of whom 76.6% (95% CI, 72.5-80.8) were poorly controlled.
      High LDL-Cholesterol above 2.0 mmol/L was found in 77.1% (95% CI 73.0-81.3) and
      Albuminuria occurred in 32.7% (95% CI 27.8-37.4). The prevalence of the other
      habits with cardiovascular disease risk were: excess alcohol intake at 26.5% (95%
      CI 27.8-37.4) and cigarette-smoking at 23.6%. A modest 23.4% of the treated
      patients with hypertension attained target blood pressure of <140/90 mmHg. Out of
      a paltry 12.5% of the statin-treated patients and others not actively treated,
      only 22.9% had LDL-Cholesterol of target <2.0 mmol/L. There were no obvious socio
      demographic and clinical determinants of poor glycaemic control. However, old age
      above 50 yrs., longer duration with diabetes above 5 yrs. and advanced stages of
      CKD were significantly associated with hypertension. Female gender and age,
      statin non-use and socio-economic factor of employment were the significant
      determinants of high levels of serum LDL-cholesterol. CONCLUSION: The majority of
      the study patients attending this government-funded health facility had high
      prevalence of cardiovascular risk factors that were inadequately controlled.
      Therefore patients with type 2 diabetes should be risk-stratified by their age,
      duration of diabetes and cardiovascular risk factor loading. Consequently,
      composite risk factor reduction strategies are needed in management of these
      patients to achieve the desired targets safely. This would be achieved through
      innovative care systems and modes of delivery which would translate into maximum
      benefit of primary cardiovascular disease prevention in those at high risk. It is
      a desirable quality objective to have a higher proportion of the patients who
      access care benefiting maximally more than the numbers we are achieving now.

PMID- 29191196
TI  - Correction to: Decisional Balance Inventory (DBI) Adolescent Form for Smoking:
      Psychometric Properties of the Persian Version.
AB  - CORRECTION: After publication of the article [1], it has been brought to our
      attention that the first and last names of the third author were transposed in
      the original article. The author was published as "Ponnet Koen" where in fact the
      correct name is "Koen Ponnet". The original article has been revised to reflect
      this.

PMID- 29191195
TI  - Maternal dietary free or bound fructose diversely influence developmental
      programming of lipogenesis.
AB  - BACKGROUND: Maternal dietary choices throughout preconception, pregnancy, and
      lactation irreversibly affect the development of fetal tissues and organs, known
      as fetal programming. Recommendations tend to emphasize reducing added sugars.
      However, the impact of maternal dietary free or bound fructose in added sugars on
      developmental programming of lipogenesis is unknown. METHODS: Virgin Sprague
      Dawley rats were randomly divided into five groups. Rats were given feed and
      plain water (control) or water containing maltodextrin (vehicle), fructose, high
      fructose corn syrup (HFCS) containing 55% fructose, sucrose (20% w/v) for 12
      weeks before mating and throughout the pregnancy and lactation periods. Body
      weight, water, and feed intake were measured throughout the study. At the end of
      the lactation period, blood was drawn to determine the fasting levels of glucose,
      insulin, triglycerides, and non-esterified fatty acids (NEFA) in blood.
      Triglycerides and acetyl Co-A Carboxylase-1 (ACC1) levels in livers were
      analyzed, and insulin resistance was calculated. RESULTS: The energy intake of
      dams in the HFCS group was higher than in the fructose group, while weight gain
      was less in the HFCS group than in the fructose group. HFCS resulted in greater
      insulin resistance in dams, whereas free fructose had a robust effect on the
      fetal programming of insulin resistance. Free fructose and HFCS in the maternal
      diet increased blood and liver triglycerides and NEFA content in pups.
      Furthermore, fructose and HFCS exposure increased phosphorylated ACC1 as compared
      to maltodextrin and control, indicating greater fatty acid synthesis in pups and
      dams. CONCLUSION: Different types of added sugar in the maternal diet have
      different metabolic effects on the developmental programming of lipogenesis.
      Consequently, high fructose intake via processed foods may increase the risk for
      chronic diseases, and free fructose might contribute to developmental programming
      of chronic diseases more than bound fructose.

PMID- 29191197
TI  - In vitro and in vivo aphrodisiac properties of the seed extract from Allium
      tuberosum on corpus cavernosum smooth muscle relaxation and sexual behavior
      parameters in male Wistar rats.
AB  - BACKGROUND: Allium tuberosum is a well-known spice as well as a herb in
      traditional Chinese medicine, used for increasing libido and treating erectile
      dysfunction. However, not many studies have been done to evaluate the sexual
      enhancing properties of A. tuberosum. The aim of this study was to evaluate the
      aphrodisiac and vasorelaxant properties of A. tuberosum on corpus cavernosum
      smooth muscle (CCSM) as well as checking the effect on enhancing male rat sexual
      behavior, libido, potency as well as its spermatogenic properties. METHOD: The
      seeds were powdered and sequentially extracted with hexane, ethyl acetate and
      butanol. Male Wistar rats were administered with graded doses of the n-BuOH
      extracts (ATB) of A. tuberosum (50, 100, 200 and 400 mg/kg) and Viagra was used
      as the positive control drug. The extract/drug was administered by gastric probe
      once daily for 45 days and the sexual behavior was analyzed by exposing the male
      rats to female rats in the estrus period. RESULTS: ATB relaxed corpus cavernosum
      smooth muscle (68.9%) at a concentration of 200 MUg/ml. The results obtained from
      the animal studies indicated that ATB significantly increased mount frequency
      (MF), intromission frequency (IF), ejaculation frequency (EF), ejaculation
      latency (EL) and markedly reduced post ejaculatory interval (PEI), mount latency
      (ML), and intromission latency (IL). Furthermore, a remarkable increase in the
      test for potency was observed as witnessed by marked increase in erections, quick
      flips, long flips and total reflex. In addition, ATB significantly improved the
      sperm viability and count as well as increased the concentrations of
      testosterone, follicle stimulating hormone (FSH), and phosphatases in the treated
      animals. CONCLUSION: Thus our results suggest that A. tuberosum could stimulate
      sexual arousal and enhance sexual execution in male rats, thus providing valuable
      experimental evidence that A. tuberosum possesses sexual enhancing properties.

PMID- 29191198
TI  - Relationship between screw sagittal angle and stress on endplate of adjacent
      segments after anterior cervical corpectomy and fusion with internal fixation: a
      Chinese finite element study.
AB  - BACKGROUND: In order to reduce the incidence of adjacent segment disease (ASD),
      the current study was designed to establish Chinese finite element models of
      normal 3rd~7th cervical vertebrae (C3-C7) and anterior cervical corpectomy and
      fusion (ACCF) with internal fixation , and analyze the influence of screw
      sagittal angle (SSA) on stress on endplate of adjacent cervical segments.
      METHODS: Mimics 8.1 and Abaqus/CAE 6.10 softwares were adopted to establish
      finite element models. RESULTS: For C4 superior endplate and C6 inferior
      endplate, their anterior areas had the maximum stress in anteflexion position,
      and their posterior areas had the maximum stress in posterior extension position.
      As SSA increased, the stress reduced. With an increase of 10 degrees  in SSA, the
      stress on anterior areas of C4 superior endplate and C6 inferior endplate reduced
      by 12.67% and 7.99% in anteflexion position, respectively. With an increase of 10
      degrees  in SSA, the stress on posterior areas of C4 superior endplate and C6
      inferior endplate reduced by 9.68% and 10.22% in posterior extension position,
      respectively. CONCLUSIONS: The current study established Chinese finite element
      models of normal C3-C7 and ACCF with internal fixation , and demonstrated that as
      SSA increased, the stress on endplate of adjacent cervical segments decreased. In
      clinical surgery, increased SSA is able to play important role in protecting the
      adjacent cervical segments and reducing the incidence of ASD.

PMID- 29191199
TI  - Paraffin immunofluorescence for detection of immune complexes in renal biopsies:
      an efficient salvage technique for diagnosis of glomerulonephritis in dogs.
AB  - BACKGROUND: Renal biopsy is an essential tool for the diagnosis of proteinuric
      kidney diseases in dogs, and evaluation of immune complexes (IC) by
      immunofluorescence (IF) of frozen sections (IF-F) is required for the diagnosis
      of IC-mediated glomerulonephritis (ICGN). However, the use of frozen sections
      from renal biopsies can have limitations. The aim of this study was to develop a
      reliable IF method using formalin-fixed and paraffin-embedded (FFPE) sections to
      detect ICs in dog ICGN. METHODS: Renal biopsy specimens were obtained from dogs
      with protein-losing nephropathies. FFPE sections were prepared, and eight antigen
      retrieval pretreatment protocols were performed: digestion with trypsin,
      microwave (MW) heating in citrate buffer (MW-CB; pH 6.0), MW heating in Tris-EDTA
      buffer (MW-TEB; pH 9.0), as well as combinations of the above, and a non-treated
      control. RESULTS: A combination of trypsin for 30 min (Try-30) and MW-TEB; pH 9.0
      was the most effective antigen retrieval pretreatment, with clear positive
      signals for IgG, IgA, IgM, and C3 detected by IF-FFPE. Granular signals, an
      important diagnostic indicator of ICGN, were clearly observed by both IF-F and IF
      FFPE after combined pretreatment with Try-30 and MW-TEB, and IgG, IgA, IgM, and
      C3 signals were almost completely matched in all samples by IF-F and IF-FFPE.
      CONCLUSION: IF-FFPE with Try-30 and MW-TEB pretreatment is a valuable technique
      for the diagnosis of renal diseases in dogs. This method could be an efficient
      tool when standard IF-F cannot be used, or does not provide useful results due to
      lack of glomeruli in the specimens for IF-F.

PMID- 29191200
TI  - Emergency general surgery in Rwandan district hospitals: a cross-sectional study
      of spectrum, management, and patient outcomes.
AB  - BACKGROUND: Management of emergency general surgical conditions remains a
      challenge in rural sub-Saharan Africa due to issues such as insufficient human
      capacity and infrastructure. This study describes the burden of emergency general
      surgical conditions and the ability to provide care for these conditions at three
      rural district hospitals in Rwanda. METHODS: This retrospective cross-sectional
      study included all patients presenting to Butaro, Kirehe and Rwinkwavu District
      Hospitals between January 1st 2015 and December 31st 2015 with emergency general
      surgical conditions, defined as non-traumatic, non-obstetric acute care surgical
      conditions. We describe patient demographics, clinical characteristics,
      management and outcomes. RESULTS: In 2015, 356 patients presented with emergency
      general surgical conditions. The majority were male (57.2%) and adults aged 15-60
      years (54.5%). The most common diagnostic group was soft tissue infections
      (71.6%), followed by acute abdominal conditions (14.3%). The median length of
      symptoms prior to diagnosis differed significantly by diagnosis type (p < 0.001),
      with the shortest being urological emergencies at 1.5 days (interquartile range
      (IQR):1, 6) and the longest being complicated hernia at 17.5 days (IQR: 1, 208).
      Of all patients, 54% were operated on at the district hospital, either by a
      general surgeon or general practitioner. Patients were more likely to receive
      surgery if they presented to a hospital with a general surgeon compared to a
      hospital with only general practitioners (75% vs 43%, p < 0.001). In addition,
      the general surgeon was more likely to treat patients with complex diagnoses such
      as acute abdominal conditions (33.3% vs 4.1%, p < 0.001) compared to general
      practitioners. For patients who received surgery, 73.3% had no postoperative
      complications and 3.2% died. CONCLUSION: While acute abdominal conditions are
      often considered the most common emergency general surgical condition in sub
      Saharan Africa, soft tissue infections were the most common in our setting. This
      could represent a true difference in epidemiology in rural settings compared to
      referral facilities in urban settings. Patients were more likely to receive an
      operation in a hospital with a general surgeon as opposed to a general
      practitioner. This provides evidence to support increasing the surgical workforce
      in district hospitals in order to increase surgical availability for patients.

PMID- 29191201
TI  - Single versus double row suture anchor fixation for greater tuberosity fractures 
      a biomechanical study.
AB  - BACKGROUND: Fractures of the humeral greater tuberosity (GT) are a frequent
      injury progressively treated with arthroscopic suture anchor repair. Yet, no
      biomechanical study has been performed comparing fixation strength of
      arthroscopic single- (SR) vs. double row (DR) fixation. METHODS: Standardized
      fractures of the greater tuberosity were created in 12 fresh frozen proximal
      humeri. After random assignation to the SR or DR group the fixed humeri were
      tested applying cyclic loading to the supraspinatus and infraspinatus tendon.
      Load to failure and fragment displacement were assessed by means of an
      electrodynamic material testing machine using an optical tracking system.
      RESULTS: Load to failure values were higher in the DR group (649 N; +/-176) than
      in the SR group (490 N; +/-145) however without statistical significance (p =
      .12). In greater tuberosity displacement of 3-5 mm surgical treatment is
      recommended. The fixing constructs in this study did not reach displacement
      landmarks of 3 or 5 mm before construct failure as shown in previous studies.
      Thus the applied traction force (N) at 1 mm displacement was analyzed. In the SR
      group the load at 1 mm displacement was 277 N; +/-46 compared to 260 N; +/-62 in
      the DR group (p = .65). CONCLUSION: The results suggest that both techniques are
      viable options for refixation of greater tuberosity fractures. LEVEL OF EVIDENCE:
      Laboratory study.

PMID- 29191202
TI  - Evaluation of an accelerated hydrogen peroxide disinfectant to inactivate porcine
      epidemic diarrhea virus in swine feces on aluminum surfaces under freezing
      conditions.
AB  - BACKGROUND: Since its emergence in 2013, porcine epidemic diarrhea virus (PEDV)
      spread rapidly throughout the country due, in part, to contaminated livestock
      trailers. The objective of this study was to test the efficacy of an accelerated
      hydrogen peroxide (AHP) disinfectant for inactivating PEDV in swine feces on
      metal surfaces under freezing conditions. One 15.24 X 15.24 X 2.54 cm aluminum
      coupon, contaminated with swine feces, and randomly matched to one pig was the
      experimental unit. Eight treatment groups representing two AHP concentrations
      (1:16 and 1:32) in a 10% propylene glycol solution, two contact times in a -10 
      degrees C freezer (40 min and 60 min), and two levels of fecal contamination (5
      mL and 10 mL) in addition to negative and positive control groups were evaluated.
      Forty 3-week-old pigs, intragastrically inoculated with the contents of the
      coupons after treatment, were used as a bioassay to determine the infectivity of
      PEDV after treatment. Infectivity was determined by detection of virus with a
      nucleocapsid (N) gene-based quantitative real-time reverse transcription
      polymerase chain reaction (RT-qPCR) on rectal swabs collected from the inoculated
      pigs on days three and seven post-inoculation. RESULTS: All post-treatment swabs
      from the negative control coupons were negative for PEDV via RT-qPCR. All post
      treatment swabs collected from coupons in the AHP disinfectant treatment groups
      and the positive control group were positive for PEDV via RT-qPCR. For the
      bioassay, no rectal swabs from pigs in the negative control (0 of 4) or the AHP
      disinfectant treatment groups (0 of 32) were positive for PEDV. Rectal swabs from
      all pigs within the positive control group (4 of 4) were positive for PEDV by RT
      qPCR. CONCLUSIONS: Under the conditions of this study, 1:16 and 1:32 dilutions of
      the AHP disinfectant successfully inactivated PEDV in swine feces on metal
      surfaces when applied at -10  degrees C with 40 or 60 min of contact time. This
      study also suggests that a positive RT-qPCR result for PEDV on an environmental
      sample should be expected when the AHP disinfectant is applied under freezing
      conditions, but does not necessarily indicate that an infectious dose of PEDV
      remains after disinfection.

PMID- 29191203
TI  - What do US and Canadian parents do to encourage or discourage physical activity
      among their 5-12 Year old children?
AB  - BACKGROUND: Parents have the potential to substantively influence their child's
      physical activity. This study identified the parenting practices of US and
      Canadian parents to encourage or discourage their 5-12 year-old child's physical
      activity and to examine differences in parenting practices by country, parental
      sex, age of child, and income. METHODS: The sample consisted of 134 US and
      Canadian parents (54.5% US; 60.4% female) recruited from a web-based panel by a
      polling firm. The parents answered open-ended questions about what they and other
      parents do to encourage or discourage their child to be active. Responses were
      coded using a scheme previously developed to code items used in the published
      literature. Coded responses were summarized by domain and dimension with
      differences in responses by country, parental sex, age of child, or household
      income assessed with a log-linear analysis. RESULTS: The 134 parents provided 649
      and 397 responses to ways that parents encourage or discourage their child's
      physical activity, respectively. Over 70% of responses for practices that
      encourage physical activity were related to structure of the environment,
      parental encouragement, and co-participation. The most common response was co
      participation in activity with the child. Of the practices that discourage
      physical activity, 67% were related to structure of the environment, lack of
      parental control, and modeling poor behaviors. The most common response was
      allowing screen time. There were no differences in response by country, parental
      sex, child age, or household income. CONCLUSIONS: Parents most often encouraged
      physical activity through structure and emotional support and discouraged
      physical activity through lack of structure and control. Understanding how
      parents influence their child's physical activity may help improve intervention
      strategies. The current results will inform the development of a physical
      activity parenting practices instrument.

PMID- 29191204
TI  - Correction to: Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial
      in moderate-to-severe acute pain after abdominal hysterectomy.
AB  - CORRECTION: Following publication of the original article [1], the authors
      reported that additional file 10 contained a typing error in the table
      "Percentage of responders (>=50% max TOTPAR) over two, four, six and eight hours
      (single-dose phase) (ITT Population)". The table is to be read as follows.

PMID- 29191205
TI  - Different effects of cardiac and diaphragm function assessed by ultrasound on
      extubation outcomes in difficult-to-wean patients: a cohort study.
AB  - BACKGROUND: Ultrasound is a convenient tool to evaluate cardiac and diaphragm
      function. The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue
      Doppler wave velocity by transthoracic echocardiography (TTE) and diaphragmatic
      excursion (DE) by diaphragm ultrasound have been confirmed in predicting
      extubation outcomes independently, however their different roles in the weaning
      process have not been determined until now. METHODS: We designed a cohort study
      to preform diaphragm ultrasound and TTE before and after the spontaneous
      breathing trial (SBT) in difficult-to-wean patients. Patients considered for
      enrollment should succeed on a SBT and have been extubated. They were followed up
      with the events of respiratory failure within 48 h, and divided into the
      respiratory failure and extubation success subgroups. Relevant risk factors
      predicting respiratory failure were analysed by a multivariate logistic
      regression model. Then, each subgroup was assessed with respect to re-intubation
      within 1 week, and divided into the re-intubation and non-intubation subgroups.
      Furthermore, relevant risk factors predicting re-intubation were also analysed in
      each subgroup. The area under the curve (AUC) and optimum cut-off value were
      identified by the receiver operating characteristic curve. RESULTS: Among 60
      patients, 29 cases developed respiratory failure within 48 h, and 14 cases were
      re-intubated or died within 1 week, respectively. Multivariate logistic
      regression analysis showed that E/Ea (average) after SBT [odds ratio (OR) 1.450,
      95% confidence intervals (CI) 1.092-1.926, P = 0.01] and left ventricular
      ejection fraction were associated with respiratory failure. The AUC of E/Ea
      (average) after SBT was 0.789, and a cut-off value >= 12.5 showed the highest
      diagnostic accuracy with a sensitivity and specificity of 72.4% and 77.4%,
      respectively. Furthermore, in the respiratory failure subgroup only DE (average)
      after SBT was associated with re-intubation (OR 0.690, CI 0.499-0.953, P =
      0.024). The AUC of DE (average) after SBT was 0.805, and a cut-off value <= 12.6
      mm showed the highest diagnostic accuracy with a sensitivity and specificity of
      80% and 68.4%, respectively. CONCLUSIONS: E/Ea (average) after SBT could help
      predict respiratory failure within 48 h. However, DE (average) after SBT could
      help predict re-intubation within 1 week in the respiratory failure subgroup.

PMID- 29191206
TI  - Optimized CEST cardiovascular magnetic resonance for assessment of metabolic
      activity in the heart.
AB  - BACKGROUND: Previous studies have linked cardiac dysfunction to loss of
      metabolites in the creatine kinase system. Chemical exchange saturation transfer
      (CEST) is a promising metabolic cardiovascular magnetic resonance (CMR) imaging
      technique and has been applied in the heart for creatine mapping. However,
      current limitations include: (a) long scan time, (b) residual cardiac and
      respiratory motion, and (c) B0 field variations induced by respiratory motion. An
      improved CEST CMR technique was developed to address these problems. METHODS:
      Animals with chronic myocardial infarction (N = 15) were scanned using the
      proposed CEST CMR technique and a late gadolinium enhancement (LGE)  sequence as
      reference. The major improvements of the CEST CMR technique are: (a) Images were
      acquired by single-shot FLASH, significantly increasing the scan efficiency. (b)
      All images were registered to reduce the residual motion. (c) The acquired Z
      spectrum was analyzed using 3-pool-model Lorentzian-line fitting to generate CEST
      signal, reducing the impact of B0 field shifting due to respiratory motion.
      Feasibility of the technique was tested in a porcine model with chronic
      myocardial infarction. CEST signal was measured in the scar, border zone and
      remote myocardium. Initial studies were performed in one patient. RESULTS: In all
      animals, healthy remote myocardial CEST signal was elevated (0.16 +/- 0.02)
      compared to infarct CEST signal (0.09 +/- 0.02, P < 0.001) and the border zone
      (0.12 +/- 0.02, P < 0.001). For both animal and patient studies, the hypointense
      regions in the CEST contrast maps closely match the bright areas in the LGE
      images. CONCLUSIONS: The proposed CEST CMR technique was developed to address
      long scan times, respiratory and cardiac motion, and B0 field variations. Lower
      CEST signal in bright region of the LGE image is consistent with the fact that
      myocardial infarction has reduced metabolic activity.

PMID- 29191207
TI  - Medical subdomain classification of clinical notes using a machine learning-based
      natural language processing approach.
AB  - BACKGROUND: The medical subdomain of a clinical note, such as cardiology or
      neurology, is useful content-derived metadata for developing machine learning
      downstream applications. To classify the medical subdomain of a note accurately,
      we have constructed a machine learning-based natural language processing (NLP)
      pipeline and developed medical subdomain classifiers based on the content of the
      note. METHODS: We constructed the pipeline using the clinical NLP system,
      clinical Text Analysis and Knowledge Extraction System (cTAKES), the Unified
      Medical Language System (UMLS) Metathesaurus, Semantic Network, and learning
      algorithms to extract features from two datasets - clinical notes from
      Integrating Data for Analysis, Anonymization, and Sharing (iDASH) data repository
      (n = 431) and Massachusetts General Hospital (MGH) (n = 91,237), and built
      medical subdomain classifiers with different combinations of data representation
      methods and supervised learning algorithms. We evaluated the performance of
      classifiers and their portability across the two datasets. RESULTS: The
      convolutional recurrent neural network with neural word embeddings trained
      medical subdomain classifier yielded the best performance measurement on iDASH
      and MGH datasets with area under receiver operating characteristic curve (AUC) of
      0.975 and 0.991, and F1 scores of 0.845 and 0.870, respectively. Considering
      better clinical interpretability, linear support vector machine-trained medical
      subdomain classifier using hybrid bag-of-words and clinically relevant UMLS
      concepts as the feature representation, with term frequency-inverse document
      frequency (tf-idf)-weighting, outperformed other shallow learning classifiers on
      iDASH and MGH datasets with AUC of 0.957 and 0.964, and F1 scores of 0.932 and
      0.934 respectively. We trained classifiers on one dataset, applied to the other
      dataset and yielded the threshold of F1 score of 0.7 in classifiers for half of
      the medical subdomains we studied. CONCLUSION: Our study shows that a supervised
      learning-based NLP approach is useful to develop medical subdomain classifiers.
      The deep learning algorithm with distributed word representation yields better
      performance yet shallow learning algorithms with the word and concept
      representation achieves comparable performance with better clinical
      interpretability. Portable classifiers may also be used across datasets from
      different institutions.

PMID- 29191208
TI  - Emotional distress and dysfunctional illness perception are associated with low
      mental and physical quality of life in Chinese breast cancer patients.
AB  - BACKGROUND: To evaluate the relationship between quality of life (QOL) and
      physical as well as psychological variables in Chinese breast cancer patients.
      METHODS: This multicenter cross-sectional study enrolled 254 Chinese breast
      cancer patients in different stages and treatment phases. They answered standard
      instruments assessing QOL (EORTC), somatic symptom severity (PHQ-15), depression
      (PHQ-9), anxiety (GAD-7), health-related anxiety (WI-7), illness perception
      (BIPQ), and sense of coherence (SOC-9). Canonical correlation was applied to
      identify the strongest correlates between the physical, emotional and social QOL
      scales and the physical and psychological variables. RESULTS: In our sample, a
      low global QOL was significantly associated with the following physical and
      psychological variables: symptom-related disability (Karnofsky Index) (r = .211,
      p < .01), somatic symptom severity (r = -.391, p < .001), depression (r = -.488,
      p < .001), anxiety (r = -.439, p < .001), health-related anxiety (r = -.398, p <
      .001), dysfunctional illness perception (r = -.411, p < .001), and sense of
      coherence (r = .371, p < .001). In the canonical correlation analysis, high
      somatic symptom severity, depression, anxiety, dysfunctional illness perception,
      and low sense of coherence showed the strongest correlations with low physical,
      emotional and social functioning. The first three significant canonical
      correlations between these two sets of variables were .78, .56, and .45.
      CONCLUSIONS: QOL in Chinese breast cancer patients is strongly associated with
      psychological factors. Our results suggest that Chinese physicians and nurses
      should incorporate these factors into their care for women with breast cancer to
      improve patients' QOL.

PMID- 29191209
TI  - Co-infection with Bartonella bacilliformis and Mycobacterium spp. in a coastal
      region of Peru.
AB  - OBJECTIVE: This study investigated an outbreak of Bartonellosis in a coastal
      region in Peru. RESULTS: A total of 70 (n = 70) samples with clinical criteria
      for the acute phase of Bartonellosis and a positive peripheral blood smear were
      included. 22.85% (n = 16) cases of the samples were positive for Bartonella
      bacilliformis by PCR and automatic sequencing. Of those positive samples, 62.5%
      (n = 10) cases were positive only for B. bacilliformis and 37.5% (n = 6) cases
      were positive to both Mycobacterium spp. and B. bacilliformis. The symptom
      frequencies were similar in patients diagnosed with Carrion's disease and those
      co-infected with Mycobacterium spp. The most common symptoms were headaches,
      followed by malaise and arthralgia.

PMID- 29191210
TI  - New clues to the nature of immunoglobulin G4-related disease: a retrospective
      Japanese multicenter study of baseline clinical features of 334 cases.
AB  - BACKGROUND: The aim was to further characterize immunoglobulin G4-related disease
      (IgG4-RD) by a large-scale multicenter study of its clinical and laboratory
      features conducted by multidisciplinary physicians of IgG4-RD in Japan. METHODS:
      Various specialists retrospectively evaluated IgG4-RD patients diagnosed between
      1996 and 2015 in five hospitals by analyzing their baseline clinical features,
      laboratory, imaging, and pathological test findings, and treatment. RESULTS: Of
      the 334 patients listed, 205 were male and median age at diagnosis was 65 years.
      The mean number of organs involved was 3.2 at diagnosis. The most frequently
      affected organs were the salivary glands, followed by the lacrimal glands, lymph
      nodes, pancreas, retroperitoneum/periaorta, kidneys, and lungs. The mean serum
      level of IgG4 was 755 mg/dl, and more than 95% of patients had elevated serum
      IgG4 levels. The median serum level of C-reactive protein (CRP) was 0.1 mg/dl and
      the level was less than 1 mg/dl in 90% of patients. A total of 34.7% of patients
      had low serum levels of C3. Serum levels of C3 and non-IgG4 IgG, calculated as
      the total IgG minus IgG4, showed an inverse correlation in patients with kidney
      lesions, while serum IgG4 levels were not correlated with serum C3 levels.
      Corticosteroid was administered in 78.0% of patients, and was effective in all.
      CONCLUSIONS: The serum CRP level is generally low and the serum IgG4 level is
      elevated in most Japanese IgG4-RD patients, in contrast to western patients.
      These original findings suggest that these two parameters in IgG4-RD differ in
      some interesting ways from those hitherto reported in western populations.
      Additional studies, especially international comparative ones, are needed to
      elucidate the extent and significance of these differences between populations.
      Attention will also have to be paid to whether the existence of such differences
      requires consideration when devising international classification criteria.

PMID- 29191211
TI  - Unexpected pulmonary tumor: metastasis from a benign uterine leiomyoma in a post
      menopausal woman: a case report.
AB  - BACKGROUND: The occurrence of lung metastasis from benign uterine leiomyomas is
      rarely reported especially in post menopausal women. The pathogenesis of these
      metastatic benign tumors still remains a subject of various speculations. CASE
      PRESENTATION: A 57-year-old woman presented with a chronic cough and dyspnea. She
      had undergone 8 years previously, hysterectomy for benign leiomyomas. A chest
      computed tomography scan showed a 4 cm solitary nodular parenchymal tumor that
      increased in size after 12 months. The histological analysis of the biopsy from
      this nodule showed a benign tumor with regular spindle cells disposed in
      intersected fascicles. At immunohistochemical analysis, the tumor cells were
      positive for smooth muscle markers and oestrogen-progesterone receptors with a
      low mitotic index assessed by Ki-67. These features were consistent with a benign
      metastasizing uterine leiomyoma. At the multidisciplinary meeting, prescription
      of an aromatase inhibitor has been decided for the patient. CONCLUSIONS: Benign
      metastasizing uterine leiomyomas of the lung are very rare tumors. Although
      extremely rare in post menopausal women, their diagnosis should be considered in
      symptomatic patients with a history of hysterectomy for leiomyomas.

PMID- 29191212
TI  - Involuntary protection against dermatosis: A preliminary observation on
      trypophobia.
AB  - OBJECTIVE: Trypophobia refers to the intense negative emotions evoked by exposure
      to repeated visual patterns like a honeycomb. We propose a cognitive mechanism
      that can explain why such negative emotions are triggered by trypophobic objects,
      primarily through automatic and involuntary avoidance of skin diseases, which is
      also called as the Involuntary Protection Against Dermatosis (IPAD) hypothesis.
      RESULTS: We asked 856 participants to evaluate the discomfort evoked by
      trypophobic images and to report their past and current skin-related medical
      problems. Results showed that participants with a history of skin problems rated
      the pictures as evoking high discomfort as compared to those without skin
      problems. We conducted another survey to replicate the original survey using
      additional 690 participants, which confirmed the reliability of the current
      findings. The current study presents preliminary observational data that supports
      the IPAD hypothesis and suggests ways to reduce maladaptive emotional reactions
      toward trypophobic objects.

PMID- 29191213
TI  - Modified pedicle screw-rod fixation versus anterior pelvic external fixation for
      the management of anterior pelvic ring fractures: a comparative study.
AB  - BACKGROUND: Anterior pelvic ring fracture, as high-energy trauma, needs to be
      effectively treated. The purpose of the current study was to evaluate the
      clinical applications of modified pedicle screw-rod fixation and anterior pelvic
      external fixation for the treatment of anterior pelvic ring fracture. METHODS:
      Either modified pedicle screw-rod fixation (modified PSRF group, N = 21) or
      anterior pelvic external fixation (APEF group, N = 22) was performed to 43
      patients, with or without fixation of posterior ring. Clinical outcomes were
      evaluated via Majeed scores. Relevant clinical evaluation indicators including
      operation time, intraoperative blood loss, hospitalization duration, and
      complications were compared between these two groups. RESULTS: The operation time
      in APEF group was significantly less than that in modified PSRF group (P <
      0.0001). No significant difference with respect to intraoperative blood loss and
      hospitalization duration between the two groups was shown (P = 0.51 and P = 0.33,
      respectively). Six patients developed surgical site infection in APEF group.
      Three patients experienced loss of fixation, and two patients experienced
      loosening of fixator in APEF group. Temporary lateral femoral cutaneous nerve
      irritation occurred in three patients in modified PSRF group while two patients
      in APEF group. One patient experienced femoral nerve palsy in modified PSRF
      group. Fractures of all patients healed well eventually. No statistical
      difference regarding Majeed evaluation scores was found between two groups.
      CONCLUSIONS: Application of both modified PSRF and APEF could provide similar
      satisfactory clinical outcomes for anterior pelvic ring fracture. Modified PSRF,
      a minimally invasive technique with the advantages of internal fixation, could be
      performed as an alternative method for instable pelvic fractures. TRIAL
      REGISTRATION: Research Registry UIN: researchregistry 2776 .

PMID- 29191214
TI  - The role of aberrant expression of T cell miRNAs affected by TNF-alpha in the
      immunopathogenesis of rheumatoid arthritis.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) can cause diverse T cell
      dysfunctions in patients with rheumatoid arthritis (RA). It is involved in the
      regulation of microRNAs (miRNAs) expression in different cell types. We
      hypothesized that the expression of T cell miRNAs would be affected by TNF-alpha,
      and these miRNAs could participate in the immunopathogenesis of RA. METHODS:
      Expression profiles of 270 human miRNAs in Jurkat cells, cultured in the presence
      or absence of TNF-alpha for 7 days were analyzed by real-time polymerase chain
      reaction. Potentially aberrantly expressed miRNAs were validated using T cell
      samples from 35 patients with RA and 15 controls. Transfection studies were
      conducted to search for gene expression and biological functions regulated by
      specific miRNAs. RESULTS: Initial analysis revealed 12 miRNAs were significantly
      lower, whereas the expression level of miR-146a was significantly higher in
      Jurkat cells after being cultured with TNF-alpha for 7 days. Decreased expression
      of miR-139-3p, miR-204, miR-760, miR-524-5p, miR-136, miR-548d-3p, miR-214, miR
      383, and miR-887 were noted in RA T cells. Expression levels of miR-139-3p, miR
      204, miR-214, and miR-760 were correlated with the use of biologic agents. The
      transfection of miR-214 mimic suppressed TNF-alpha-mediated apoptosis of Jurkat
      cells. Increased phosphorylation of extracellular regulating kinase (ERK) and c
      Jun N-terminal kinase (JNK) was noted in RA T cells and Jurkat cells after TNF
      alpha exposure. Transfection of Jurkat cells with miR-214 mimic suppressed both
      the basal and TNF-alpha-mediated ERK and JNK phosphoryation. CONCLUSIONS: Among T
      cell miRNAs affected by TNF-alpha, the expression levels of nine miRNAs were
      decreased in T cells from patients with RA. The expression levels of miR-139-3p,
      miR-204, miR-214, and miR-760 increased in RA patients receiving biologic agents.
      The transfection of miR-214 reversed the TNF-alpha-mediated cells apoptosis and
      inhibited the phosphorylation of ERK and JNK in Jurkat cells.

PMID- 29191215
TI  - Domestication of self-splicing introns during eukaryogenesis: the rise of the
      complex spliceosomal machinery.
AB  - : ?: The spliceosome is a eukaryote-specific complex that is essential for the
      removal of introns from pre-mRNA. It consists of five small nuclear RNAs (snRNAs)
      and over a hundred proteins, making it one of the most complex molecular
      machineries. Most of this complexity has emerged during eukaryogenesis, a period
      that is characterised by a drastic increase in cellular and genomic complexity.
      Although not fully resolved, recent findings have started to shed some light on
      how and why the spliceosome originated. In this paper we review how the
      spliceosome has evolved and discuss its origin and subsequent evolution in light
      of different general hypotheses on the evolution of complexity. Comparative
      analyses have established that the catalytic core of this ribonucleoprotein (RNP)
      complex, as well as the spliceosomal introns, evolved from self-splicing group II
      introns. Most snRNAs evolved from intron fragments and the essential Prp8 protein
      originated from the protein that is encoded by group II introns. Proteins that
      functioned in other RNA processes were added to this core and extensive
      duplications of these proteins substantially increased the complexity of the
      spliceosome prior to the eukaryotic diversification. The splicing machinery
      became even more complex in animals and plants, yet was simplified in eukaryotes
      with streamlined genomes. Apparently, the spliceosome did not evolve its
      complexity gradually, but in rapid bursts, followed by stagnation or even
      simplification. We argue that although both adaptive and neutral evolution have
      been involved in the evolution of the spliceosome, especially the latter was
      responsible for the emergence of an enormously complex eukaryotic splicing
      machinery from simple self-splicing sequences. REVIEWERS: This article was
      reviewed by W. Ford Doolittle, Eugene V. Koonin and Vivek Anantharaman.

PMID- 29191216
TI  - COSUMO: study protocol for the development of a core outcome set for efficacy and
      effectiveness trials in posterior segment-involving uveitis.
AB  - BACKGROUND: Uveitis, a group of disorders characterised by intraocular
      inflammation, causes 10-15% of total blindness in the developed world. The most
      sight-threatening uveitis affects the posterior segment of the eye (posterior
      segment involving uveitis (PSIU)). Numerous different outcomes have been used in
      clinical trials evaluating alternative treatments for uveitis, limiting inter
      trial comparison and aggregation of data. We aim to develop a core outcome set
      (COS) that would provide a standardised set of outcomes to be measured and
      reported in all effectiveness trials for PSIU. METHODS: A three-phase design will
      be used informed by recommendations from the Core Outcome Measures in
      Effectiveness Trials (COMET) initiative. Phase 1: a comprehensive list of
      outcomes will be identified through both a systematic review of effectiveness
      trials of PSIU and qualitative research with stakeholders. The qualitative study
      will comprise focus groups with patients and their carers in parallel with one-to
      one telephone interviews with health professionals and policy-makers. In the
      focus groups, patients will be grouped according to whether or not their uveitis
      is complicated by the sight-threatening condition uveitic macular oedema (UMO)
      since it is hypothesised that the presence of UMO may significantly impact on
      patient experience of PSIU. Phase 2: Delphi methodology will be used to reduce
      the range of potential outcomes for the core set. Up to three Delphi rounds will
      be used through an online survey. Participants will be asked to rate the
      importance of each outcome on a 9-point Likert scale where 9 is most important.
      Phase 3: a consensus meeting will be held with key stakeholders to discuss the
      Delphi results and ratify the final outcomes to be included in the COS.
      DISCUSSION: The development of an agreed COS for PSIU would help ensure that
      outcomes which matter to key stakeholders are captured and reported in a
      consistent way. A COS for PSIU would allow greater comparison and aggregation of
      data across trials for the better evaluation of established and emerging
      therapies through evidence synthesis and meta-analysis to inform clinical
      guidelines and health policy. TRIAL REGISTRATION: COMET. http://comet
      initiative.org/studies/details/640 . August 2015.

PMID- 29191217
TI  - Multi-level comparisons of cloacal, skin, feather and nest-associated microbiota
      suggest considerable influence of horizontal acquisition on the microbiota
      assembly of sympatric woodlarks and skylarks.
AB  - BACKGROUND: Working toward a general framework to understand the role of
      microbiota in animal biology requires the characterisation of animal-associated
      microbial communities and identification of the evolutionary and ecological
      factors shaping their variation. In this study, we described the microbiota in
      the cloaca, brood patch skin and feathers of two species of birds and the
      microbial communities in their nest environment. We compared patterns of
      resemblance between these microbial communities at different levels of biological
      organisation (species, individual, body part) and investigated the phylogenetic
      structure to deduce potential microbial community assembly processes. RESULTS:
      Using 16S rRNA gene amplicon data of woodlarks (Lullula arborea) and skylarks
      (Alauda arvensis), we demonstrated that bird- and nest-associated microbiota
      showed substantial OTU co-occurrences and shared dominant taxonomic groups,
      despite variation in OTU richness, diversity and composition. Comparing host
      species, we uncovered that sympatric woodlarks and skylarks harboured similar
      microbiota, dominated by Proteobacteria, Firmicutes, Actinobacteria,
      Bacteroidetes and Acidobacteria. Yet, compared with the nest microbiota that
      showed little variation, each species' bird-associated microbiota displayed
      substantial variation. The latter could be partly (~ 20%) explained by
      significant inter-individual differences. The various communities of the bird's
      body (cloaca, brood patch skin and feathers) appeared connected with each other
      and with the nest microbiota (nest lining material and surface soil). Communities
      were more similar when the contact between niches was frequent or intense.
      Finally, bird microbiota showed significant phylogenetic clustering at the tips,
      but not at deeper branches of the phylogeny. CONCLUSIONS: Our interspecific
      comparison suggested that the environment is more important than phylogeny in
      shaping the bird-associated microbiotas. In addition, variation among individuals
      and among body parts suggested that intrinsic or behavioural differences among
      females and spatial heterogeneity among territories contributed to the microbiome
      variation of larks. Modest but significant phylogenetic clustering of cloacal,
      skin and feather microbiotas suggested weak habitat filtering in these niches. We
      propose that lark microbiota may be primarily, but not exclusively, shaped by
      horizontal acquisition from the regional bacterial pool at the breeding site.
      More generally, we hypothesise that the extent of ecological niche-sharing by
      avian (or other vertebrate) hosts may predict the convergence of their
      microbiota.

PMID- 29191218
TI  - Analysis of choroidal and central foveal thicknesses in acute anterior uveitis by
      enhanced-depth imaging optical coherence tomography.
AB  - BACKGROUND: Currently, there are a limited number of reports of structural
      changes in the retina and choroid in acute anterior uveitis (AAU). The aim of
      this study was to evaluate choroidal and central foveal thicknesses during
      episodes of AAU. METHODS: The medical records of 120 patients with AAU and 120
      healthy subjects matched for age, sex, and spherical equivalent of refractive
      error were reviewed. Subjects were divided into group 1 (AAU-affected eyes), 2
      (unaffected fellow eyes), and 3 (healthy control eyes). RESULTS: In the uveitis
      group, etiologic diagnoses included human leukocyte antigen (HLA)-B27-associated
      (n = 71) and idiopathic (n = 49) AAU. The mean subfoveal choroidal thicknesses
      (SFCTs) in groups 1-3 were 326.7 +/- 64.2, 296.1 +/- 66.6, and 294.9 +/- 41.7
      MUm, respectively. The corresponding mean central foveal thicknesses (CFTs) were
      273.5 +/- 29.3, 264.4 +/- 24.6, and 263.0 +/- 30.8 MUm, respectively. The AAU
      group exhibited a significantly greater SFCT than the control groups (P < .001).
      Relative to the control group, while eyes with idiopathic AAU exhibited a
      significantly greater CFT, those with HLA-B27-associated AAU exhibited no such
      significant difference. Anterior chamber cell grade was not associated with SFCT
      or CFT. CONCLUSIONS: The SFCT increased significantly during AAU. This indicates
      the importance of OCT examination for detection of subclinical choroidal and
      retinal changes in all types of AAU.

PMID- 29191220
TI  - Type IV dual left anterior descending coronary artery: a case report.
AB  - BACKGROUND: Dual left anterior descending (LAD) artery or duplication of LAD is a
      rarely reported coronary anomaly, consisting of two branches supplying the usual
      distribution of the LAD. Type IV dual LAD, in which a short LAD arises from the
      left main coronary artery and a long LAD arises from the right coronary artery is
      remarkably rare, and has not been reported in a Bangladeshi subject. CASE
      PRESENTATION: We describe the case of a 70-year old Bangladeshi male who
      presented with breathlessness in the background of a prior inferior myocardial
      infarction. Coronary angiography revealed an anomalous dual LAD. The short LAD
      which arose from the left main coronary artery gave off the first septal branch
      and terminated after giving off a large diagonal branch which continued further
      down towards the apex. The long LAD arose from the proximal right coronary artery
      and after traversing a distance, arrived at the interventricular septum,
      terminating at the apex after giving off diagonal branches. The right coronary
      artery was totally occluded from its early mid part and well-collateralized with
      retrograde flow from the left system. CONCLUSION: We describe a case with unique
      variation of dual LAD type IV, which has previously not been described in a
      Bangladeshi subject thus far. Coronary angiography is vital to determine this
      coronary anomaly, which is usually detected incidentally on routine angiography
      for chest pain, sometimes with involvement of significant lesion of other
      coronary arteries, as in this case.

PMID- 29191221
TI  - Increased synovial lipodystrophy induced by high fat diet aggravates synovitis in
      experimental osteoarthritis.
AB  - BACKGROUND: Metabolic syndrome (MetS) may be associated with knee osteoarthritis
      (OA), but the association between the individual components and OA are not well
      understood. We aimed to study the effect of hypercholesterolemia on synovial
      inflammation in knee OA. METHODS: OA was surgically induced in rabbits fed with
      standard diet (OA group, n = 10) or in rabbits fed with high fat diet (OA-HFD, n
      = 10). Healthy rabbits receiving standard diet (Control, n = 10) or fed with HFD
      (HFD, n = 6) were also monitored. Twelve weeks after OA induction, synovial
      membranes were isolated and processed for studies. RESULTS: Animals fed HFD
      showed higher levels of total serum cholesterol, triglycerides and C-reactive
      protein than control rabbits. Twelve weeks after OA induction, synovial membrane
      inflammation and macrophage infiltration were increased in rabbits with OA,
      particularly in the OA-HFD group. Extensive decrease of synovial adipose tissue
      area, adipocyte size and perilipin-1A synthesis were observed in the OA-HFD group
      in comparison to the OA and control groups. The HFD further increased the
      proinflammatory mediators IL-1beta, IL-6 and TNF in the OA synovium. However, the
      synovial gene expression of adipokines, such as leptin and adiponectin, were
      markedly decreased in the rabbits with OA, especially in the OA-HFD group, in
      correlation with adipose tissue loss. However, circulating leptin was upregulated
      in the HFD and OA-HFD groups. CONCLUSION: Our results indicate that a HFD is an
      aggravating factor worsening synovial membrane inflammation during OA, guided by
      increased infiltration of macrophages and removal of the adipose tissue, together
      with a remarkable presence of proinflammatory factors. Synovial adipocytes and
      dyslipemia could probably play pivotal roles in OA joint deterioration in
      patients with MetS, supporting that the link between obesity and OA transcends
      mechanical loading.

PMID- 29191219
TI  - Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU
      hyperphosphorylation, increased amyloid levels, and GSK3B activation.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia,
      affecting one in eight adults over 65 years of age. The majority of AD cases are
      sporadic, with unknown etiology, and only 5% of all patients with AD present the
      familial monogenic form of the disease. In the present study, our aim was to
      establish an in vitro cell model based on patient-specific human neurons to study
      the pathomechanism of sporadic AD. METHODS: We compared neurons derived from
      induced pluripotent stem cell (iPSC) lines of patients with early-onset familial
      Alzheimer's disease (fAD), all caused by mutations in the PSEN1 gene; patients
      with late-onset sporadic Alzheimer's disease (sAD); and three control individuals
      without dementia. The iPSC lines were differentiated toward mature cortical
      neurons, and AD pathological hallmarks were analyzed by RT-qPCR, enzyme-linked
      immunosorbent assay, and Western blotting methods. RESULTS: Neurons from patients
      with fAD and patients with sAD showed increased phosphorylation of TAU protein at
      all investigated phosphorylation sites. Relative to the control neurons, neurons
      derived from patients with fAD and patients with sAD exhibited higher levels of
      extracellular amyloid-beta 1-40 (Abeta1-40) and amyloid-beta 1-42 (Abeta1-42).
      However, significantly increased Abeta1-42/Abeta1-40 ratios, which is one of the
      pathological markers of fAD, were observed only in samples of patients with fAD.
      Additionally, we detected increased levels of active glycogen synthase kinase 3
      beta, a physiological kinase of TAU, in neurons derived from AD iPSCs, as well as
      significant upregulation of amyloid precursor protein (APP) synthesis and APP
      carboxy-terminal fragment cleavage. Moreover, elevated sensitivity to oxidative
      stress, as induced by amyloid oligomers or peroxide, was detected in both fAD-
      and sAD-derived neurons. CONCLUSIONS: On the basis of the experiments we
      performed, we can conclude there is no evident difference except secreted Abeta1
      40 levels in phenotype between fAD and sAD samples. To our knowledge, this is the
      first study in which the hyperphosphorylation of TAU protein has been compared in
      fAD and sAD iPSC-derived neurons. Our findings demonstrate that iPSC technology
      is suitable to model both fAD and sAD and may provide a platform for developing
      new treatment strategies for these conditions.

PMID- 29191222
TI  - Magico-religious and social belief of tribals of district Udaipur, Rajasthan.
AB  - BACKGROUND: Religious beliefs and practices have long influenced human
      perceptions and uses of nature. Animals in particular play a prominent role in
      magico-religious practices and provide historical and cultural depth of these
      relationships. Understanding human-faunal relations is often fundamental to the
      cause of meaningful wildlife conservation. This study investigates the domestic
      and wild harvested species used for spiritual and religious purposes among the
      tribals of six tehsils of Udaipur district. METHODS: The ethnozoological data
      were obtained by an emic approach, applying different tools such as semi
      structured interviews, participatory rural appraisal, key informant interviews,
      and focus group discussions. The scientific name and species of animals were
      identified using relevant and standard literature. Present investigation is a
      part of major concept worked out for study on tribal people and their beliefs.
      Ethnozoological information was collected by interview of 150 tribals. The
      questionnaire was prepared in Hindi keeping all parameters in mind. A total of 55
      respondents (35 males and 20 females) answered to the magico-religious parameter.
      The collected data were analyzed through informant fidelity level (FL). RESULTS:
      The present study was undertaken to have an insight of the ethnozoological uses
      of animals prevalent in Bhil, Meena, and Kathodi tribes inhabiting the Udaipur
      district of Rajasthan. A total of 25 animals used for magico-religious and social
      purposes were recorded from the study area. Out of the total number of animals,
      60% (15) were mammals, 24% (6) were birds, 12% (3) were reptiles, and the rest 4%
      (1) were the mollusks. Of the total ethnozoological practices, 64% fall in the
      magico-religious category, 12% in socio-cultural category, 12% in the category of
      ethnomusical, and 12% in the category of taboos. CONCLUSIONS: The tribal people
      maintain strong ties with animals at both the material and spiritual level. Study
      reveals that traditional people depend on local therapies either magico-religious
      or natural ones in absence of awareness, modern medical facilities, expensive
      drugs, and poor transportation. However, the use of animal material in such
      practices is on a decline.

PMID- 29191223
TI  - Resistin upregulates chemokine production by fibroblast-like synoviocytes from
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Adipokines are bioactive hormones secreted by adipose tissues.
      Resistin, an adipokine, plays important roles in the regulation of insulin
      resistance and inflammation. Resistin levels are known to be increased in the
      serum and synovial fluid of rheumatoid arthritis (RA) patients. However, the
      pathogenic role of resistin in RA has not yet been elucidated. METHODS: The
      expression of resistin and adenylate cyclase-associated protein 1 (CAP1), a
      receptor for resistin, was examined immunohistochemically in synovial tissue.
      CAP1 expression in in vitro cultured fibroblast-like synoviocytes (FLSs) was
      assessed with a reverse transcription-polymerase chain reaction (PCR) and western
      blotting. The gene expression of resistin-stimulated FLSs was evaluated by RNA
      sequencing (RNA-Seq) and quantitative real-time PCR. Concentrations of chemokine
      (C-X-C motif) ligand (CXCL) 8, chemokine (C-C motif) ligand (CCL) 2, interleukin
      (IL)-1beta, IL-6 and IL-32 in culture supernatants were measured by enzyme-linked
      immunosorbent assay. Small interfering RNA (siRNA) for CAP1 was transfected into
      FLSs in order to examine inhibitory effects. RESULTS: The expression of resistin
      and CAP1 in synovial tissue was stronger in RA than in osteoarthritis (OA).
      Resistin was expressed by macrophages in the RA synovium, while CAP1 was
      expressed by macrophages, FLSs and endothelial cells. In vitro cultured RA FLSs
      also expressed CAP1. RNA-Seq revealed that the expression levels of 18 molecules
      were more than twofold higher in resistin-stimulated FLSs than in unstimulated
      FLSs. Seven chemokines, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, and CCL2, were
      included among the 18 molecules. Increases induced in the expression of CXCL1,
      CXCL8, and CCL2 by the resistin stimulation were confirmed by real-time PCR. The
      stimulation with resistin increased the protein levels of CXCL8 and CCL2 produced
      by RA FLSs, and the upregulated expression of CXCL8 was inhibited by the
      abrogation of CAP1 by siRNA for CAP1. Production of IL-6 by FLSs was also
      increased by resistin. Expression of IL-1beta and IL-32 was not detected by
      ELISA. CONCLUSIONS: Resistin contributes to the pathogenesis of RA by increasing
      chemokine production by FLSs via CAP1 in synovial tissue.

PMID- 29191224
TI  - I knew how it feels but couldn't save my daughter; testimony of an Ethiopian
      mother on female genital mutilation/cutting.
AB  - BACKGROUND: World Health Organization defines female genital mutilation/cutting
      as all procedures that involve partial or total removal of the external female
      genitalia, or other injury to the female genital organs for non-medical reasons.
      The practice is common in Ethiopia, especially among Somali (99%) ethnic groups.
      Even though FGM/C is labeled illegal practice according to the revised 2005 Penal
      Code of the country, the practice is still responsible for misery of many girls
      in Ethiopia. METHODS: This personal testimony is presented using woman's own
      words. Data were collected through in-depth interview with a woman at Gursum
      health center, Somali regional state, eastern Ethiopia on June 19/2016. The
      interview was conducted in a private environment and original names were changed
      to overcome ethical concerns. Informed written consent was obtained from the
      participant prior to data collection. The interview was audio-taped using a
      digital voice recorder, later transcribed and translated verbatim from the local
      language, Amharic to English. RESULTS: The study participant described a range of
      experiences she had during her own and her daughter's circumcision. Three themes
      emerged from the woman's description: womanhood, social pressure and
      stigmatization of uncircumcised women and uncertain future. CONCLUSION: Even
      though the national prevalence may show a decline, FGM/C is still practiced
      underground. Thus, anti-FGM/C interventions shall take in to account elders
      influence and incorporate a human rights approach rather than relying merely on
      the dire health consequences. Further exploration of the determinants of FGM/C on
      a wider scale is recommended.

PMID- 29191226
TI  - Antibacterial and antifungal activities and phytochemical profile of leaf extract
      from different extractants of Ricinus communis against selected pathogens.
AB  - OBJECTIVES: Ricinus communis leaves are used in herbal preparations for treating
      candidiasis, skin and wound infections in Ghana. This study aimed at comparing
      the phytochemical profile of aqueous, methanol, petroleum ether, ethyl acetate
      and ethanolic extracts of the leaves of Ricinus communis and determine the growth
      inhibitory activities, bactericidal, bacteriostatic and fungicidal effects of the
      respective extracts on Escherichia coli, Staphylococcus aureus, Pseudomonas
      aeruginosa, Klebsiella pneumonaie and Candida albicans. RESULTS: The aqueous,
      methanol and ethanol extracts were shown to contain most of the phytochemicals
      analyzed. All solvents extracts exhibited inhibitory activity against the growth
      of all microorganisms under study. The methanol extract showed highest zones of
      inhibition and was found to be statistically significant (P < 0.05) compared to
      other solvents extracts. All solvents extracts exhibited both bacteriostatic and
      bactericidal effects on the test organisms at varying concentration, with MIC
      values ranging from 3.13 to 25.0 mg/ml and MBCs were from 200 to 400 mg/ml. MFCs
      of Candida albicans was between 200 and 400 mg/l. Our data confirm the anti
      bacterial and anti-fungal properties of R. communis and showed that the
      biologically relevant phytochemicals from the leaves of this plant can be
      extracted with the solvents aqueous, methanol and ethanol.

PMID- 29191225
TI  - Landscape and evolution of tissue-specific alternative polyadenylation across
      Drosophila species.
AB  - BACKGROUND: Drosophila melanogaster has one of best-described transcriptomes of
      any multicellular organism. Nevertheless, the paucity of 3'-sequencing data in
      this species precludes comprehensive assessment of alternative polyadenylation
      (APA), which is subject to broad tissue-specific control. RESULTS: Here, we
      generate deep 3'-sequencing data from 23 developmental stages, tissues, and cell
      lines of D. melanogaster, yielding a comprehensive atlas of ~ 62,000
      polyadenylated ends. These data broadly extend the annotated transcriptome,
      identify ~ 40,000 novel 3' termini, and reveal that two-thirds of Drosophila
      genes are subject to APA. Furthermore, we dramatically expand the numbers of
      genes known to be subject to tissue-specific APA, such as 3' untranslated region
      (UTR) lengthening in head and 3' UTR shortening in testis, and characterize new
      tissue and developmental 3' UTR patterns. Our thorough 3' UTR annotations permit
      reassessment of post-transcriptional regulatory networks, via conserved miRNA and
      RNA binding protein sites. To evaluate the evolutionary conservation and
      divergence of APA patterns, we generate developmental and tissue-specific 3'-seq
      libraries from Drosophila yakuba and Drosophila virilis. We document broadly
      analogous tissue-specific APA trends in these species, but also observe
      significant alterations in 3' end usage across orthologs. We exploit the
      population of functionally evolving poly(A) sites to gain clear evidence that
      evolutionary divergence in core polyadenylation signal (PAS) and downstream
      sequence element (DSE) motifs drive broad alterations in 3' UTR isoform
      expression across the Drosophila phylogeny. CONCLUSIONS: These data provide a
      critical resource for the Drosophila community and offer many insights into the
      complex control of alternative tissue-specific 3' UTR formation and its
      consequences for post-transcriptional regulatory networks.

PMID- 29191227
TI  - Performance of MTBDRplus assay in detecting multidrug resistant tuberculosis at
      hospital level.
AB  - OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) case finding progressively
      increased in Ethiopia mainly as a result of the utilization of World Health
      Organization (WHO)-endorsed rapid technologies including MTBDRplus assay.
      However, there is inadequate data on routine testing performance of the MTBDRplus
      assay. Consequently, the aim of the study was to assess the routine performance
      of the MTBDRplus assay in detecting MDR-TB at St. Peter's TB Specialized
      Hospital. RESULTS: The sensitivity and specificity of MTBDRplus in detecting
      isoniazid (INH) resistance were 96.3 and 100%, respectively. While for rifampicin
      (RIF) 100% was recorded for both. Similarly, a sensitivity of 97.96% and a
      specificity of 100% was measured for detecting MDR-TB. Among 49 MTBDRplus RIF
      resistant isolates, 46 (93.9%) strains had rpoB mutation. S531L was the most
      common rpoB mutant (81.6% of RIF resistant cases). All MTBDRplus INH resistant
      isolates (n = 52) had S315T1 katG mutation.

PMID- 29191228
TI  - The oncology nurse coordinator: role perceptions of staff members and nurse
      coordinators.
AB  - BACKGROUND: There is extensive evidence that the role of nurse coordinators is
      beneficial for patients. Nurse coordinators are more available to patients
      compared to general registered nurses, know better to control symptoms and work
      as team players with multiple care providers. Despite its significance, there is
      a dearth of literature on the subject in Israel and a lack of clarity regarding
      the definitions of the role in terms of responsibilities and authorities. The aim
      of the study is to: To examine how the role of nurse oncology coordinator is
      implemented in various fields of oncology and to describe the actual performance
      of different kinds of oncology nurse coordinators and staff perceptions regarding
      this role in one tertiary hospital in Jerusalem. METHODS: A phenomenological
      approach was used to explore the participants' experiences and views of nurse
      coordinators' performance. We conducted a qualitative study using in-depth semi
      structured interviews. Interviewees included 30 employees from different levels
      of the hospitals, and leading figures associated with oncology medicine outside
      of the hospital: Nurses and physicians of the Sharett Oncology Institute of
      Hadassah Ein Kerem Hospital in Jerusalem, the administrative staff of Hadassah
      Ein Kerem Hospital, head nurses of the Israel Cancer Association, the chairperson
      of the Non-Profit Organization of Oncology Nurses, nurse directors at the
      Ministry of Health Nursing Division, and seven nurse coordinators at Hadassah Ein
      Kerem Hospital in diverse fields of oncology. RESULTS: The nurse coordinator is
      perceived as an important staff member providing care to cancer patients. Several
      key elements were found to be common features in the work of all nurse
      coordinators: emotional support, guidance to patients, and coordination of
      patients' care. CONCLUSIONS: The nurse coordinator plays a noteworthy role in the
      health care system. In view of the variety of roles that the nurse coordinator
      assumes in different units, performance standards must be adapted to the
      performance areas for each unit, as well as nurses' professional development
      requirements. Changes in a service organization and careful attention to the
      continuum of care highlight the need to develop and to strengthen the role of a
      nurse who coordinates treatment over the entire continuum of care, both in the
      hospital and in the community.

PMID- 29191229
TI  - Medical students as health coaches, and more: adding value to both education and
      patient care.
AB  - New ways of thinking about medicine and health care demand new methods in medical
      education. Over the past two decades, as both the practice and the study of
      medicine have become increasingly concerned with demonstrable outcomes, medical
      schools have developed new curricula in health systems science and are
      increasingly emphasizing students' development and demonstration of skills
      essential to a systems-based, outcomes-oriented practice environment.Polak and
      colleagues recently reported the development in Israel of one such curriculum, in
      lifestyle medicine, that includes opportunities for students to adopt the role of
      health coach. This commentary describes additional recent curricular developments
      elsewhere with similar goals, but utilizing more ambitious approaches that embed
      students in medical practices and provide meaningful, ongoing responsibility for
      assisting in the care of patients. These emerging new models for ambulatory care
      education, through a construct known as "value added education," can
      simultaneously benefit both educational and patient care outcomes.

PMID- 29191231
TI  - Assessing loss to follow-up in the MObile Technology for Improved Family Planning
      (MOTIF) randomised controlled trial.
AB  - BACKGROUND: Loss to follow-up (LTFU) in clinical trials is an important source of
      bias that can affect statistical power and generalisability of findings. The aim
      of this paper is to assess factors associated with LTFU in the MObile Technology
      for Improved Family Planning (MOTIF) trial in Cambodia and compare how the result
      might have varied using different analytical methods. METHODS: Follow-up in the
      MOTIF trial was 86% at 4 months and 66% at 12 months. For the primary analysis,
      we undertook a complete case analysis, similar to the approach used in similar
      trials of interventions delivered by mobile phone to increase contraception use.
      We conducted an exploratory analysis and found that factors associated with LTFU
      were young age, lower socio-economic status, not planning to use post-abortion
      contraception, availability of phone credit and not providing additional contact
      numbers. We then undertook two analyses to estimate the effect of the
      intervention on the primary outcome at 4 and 12 months for comparison with the
      complete case analysis. First, we undertook multiple imputation, and second we
      conducted an analysis treating all participants' LTFU as non-users of
      contraception. RESULTS: Using multiple imputation, we found that the risk ratio
      was slightly increased at 4 months and slightly decreased at 12 months compared
      with the complete case analysis. When counting all participants' LTFU as non
      users of contraception, we observed that, compared with the complete case
      analysis, the risk ratio was slightly decreased at 4 months and slightly
      increased at 12 months. Despite the changes in the risk ratio, use of the
      different analytical methods did not result in an effect using the complete case
      analysis becoming statistically significant or vice versa. CONCLUSION: Future
      studies assessing contraception use might anticipate increased attrition amongst
      younger participants, those of lower socio-economic status or those who do not
      provide additional contact details. Attrition could be reduced by collecting as
      many contact details as possible, by providing incentives and possibly by
      enhanced counselling to groups at higher risk of LTFU on recruitment. Multiple
      imputation should be considered in addition to complete case analysis if LTFU not
      missing at random is expected or observed. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01823861 . Registered on 30 March 2013.

PMID- 29191230
TI  - Implementation fidelity trajectories of a health promotion program in
      multidisciplinary settings: managing tensions in rehabilitation care.
AB  - BACKGROUND: Although the importance of evaluating implementation fidelity is
      acknowledged, little is known about heterogeneity in fidelity over time. This
      study aims to generate insight into the heterogeneity in implementation fidelity
      trajectories of a health promotion program in multidisciplinary settings and the
      relationship with changes in patients' health behavior. METHODS: This study used
      longitudinal data from the nationwide implementation of an evidence-informed
      physical activity promotion program in Dutch rehabilitation care. Fidelity scores
      were calculated based on annual surveys filled in by involved professionals (n =
      +/- 70). Higher fidelity scores indicate a more complete implementation of the
      program's core components. A hierarchical cluster analysis was conducted on the
      implementation fidelity scores of 17 organizations at three different time
      points. Quantitative and qualitative data were used to explore organizational and
      professional differences between identified trajectories. Regression analyses
      were conducted to determine differences in patient outcomes. RESULTS: Three
      trajectories were identified as the following: 'stable high fidelity' (n = 9),
      'moderate and improving fidelity' (n = 6), and 'unstable fidelity' (n = 2). The
      stable high fidelity organizations were generally smaller, started earlier, and
      implemented the program in a more structured way compared to moderate and
      improving fidelity organizations. At the implementation period's start and end,
      support from physicians and physiotherapists, professionals' appreciation, and
      program compatibility were rated more positively by professionals working in
      stable high fidelity organizations as compared to the moderate and improving
      fidelity organizations (p < .05). Qualitative data showed that the stable high
      fidelity organizations had often an explicit vision and strategy about the
      implementation of the program. Intriguingly, the trajectories were not associated
      with patients' self-reported physical activity outcomes (adjusted model beta = -
      651.6, t(613) = - 1032, p = .303). CONCLUSIONS: Differences in organizational
      level implementation fidelity trajectories did not result in outcome differences
      at patient-level. This suggests that an effective implementation fidelity
      trajectory is contingent on the local organization's conditions. More
      specifically, achieving stable high implementation fidelity required the
      management of tensions: realizing a localized change vision, while safeguarding
      the program's standardized core components and engaging the scarce physicians
      throughout the process. When scaling up evidence-informed health promotion
      programs, we propose to tailor the management of implementation tensions to local
      organizations' starting position, size, and circumstances. TRIAL REGISTRATION:
      The Netherlands National Trial Register NTR3961 . Registered 18 April 2013.

PMID- 29191232
TI  - Active versus passive adverse event reporting after pediatric chiropractic manual
      therapy: study protocol for a cluster randomized controlled trial.
AB  - BACKGROUND: Patient safety performance can be assessed with several systems,
      including passive and active surveillance. Passive surveillance systems provide
      opportunity for health care personnel to confidentially and voluntarily report
      incidents, including adverse events, occurring in their work environment. Active
      surveillance systems systematically monitor patient encounters to seek detailed
      information about adverse events that occur in work environments; unlike passive
      surveillance, active surveillance allows for collection of both numerator (number
      of adverse events) and denominator (number of patients seen) data. Chiropractic
      manual therapy is commonly used in both adults and children, yet few studies have
      been done to evaluate the safety of chiropractic manual therapy for children. In
      an attempt to evaluate this, this study will compare adverse event reporting in
      passive versus active surveillance systems after chiropractic manual therapy in
      the pediatric population. METHODS/DESIGN: This cluster randomized controlled
      trial aims to enroll 70 physicians of chiropractic (unit of randomization) to
      either passive or active surveillance system to report adverse events that occur
      after treatment for 60 consecutive pediatric (13 years of age and younger)
      patient visits (unit of analysis). A modified enrollment process with a two-phase
      consent procedure will be implemented to maintain provider blinding and minimize
      dropouts. The first phase of consent is for the provider to confirm their
      interest in a trial investigating the safety of chiropractic manual therapy. The
      second phase ensures that they understand the specific requirements for the group
      to which they were randomized. Percentages, incidence estimates, and 95%
      confidence intervals will be used to describe the count of reported adverse
      events in each group. The primary outcome will be the number and quality of the
      adverse event reports in the active versus the passive surveillance group. With
      80% power and 5% one-sided significance level, the sample size was calculated to
      be 35 providers in each group, which includes an 11% lost to follow-up of
      chiropractors and 20% of patient visits. DISCUSSION: This study will be the first
      direct comparison of adverse event reporting using passive versus active
      surveillance. It is also the largest prospective evaluation of adverse events
      reported after chiropractic manual therapy in children, identified as a major gap
      in the academic literature. TRIAL REGISTRATION: ClinicalTrials.gov, ID:
      NCT02268331 . Registered on 10 October 2014.

PMID- 29191233
TI  - Functional dissection of Drosophila melanogaster SUUR protein influence on
      H3K27me3 profile.
AB  - BACKGROUND: In eukaryotes, heterochromatin replicates late in S phase of the cell
      cycle and contains specific covalent modifications of histones. SuUR mutation
      found in Drosophila makes heterochromatin replicate earlier than in wild type and
      reduces the level of repressive histone modifications. SUUR protein was shown to
      be associated with moving replication forks, apparently through the interaction
      with PCNA. The biological process underlying the effects of SUUR on replication
      and composition of heterochromatin remains unknown. RESULTS: Here we performed a
      functional dissection of SUUR protein effects on H3K27me3 level. Using hidden
      Markow model-based algorithm we revealed SuUR-sensitive chromosomal regions that
      demonstrated unusual characteristics: They do not contain Polycomb and require
      SUUR function to sustain H3K27me3 level. We tested the role of SUUR protein in
      the mechanisms that could affect H3K27me3 histone levels in these regions. We
      found that SUUR does not affect the initial H3K27me3 pattern formation in
      embryogenesis or Polycomb distribution in the chromosomes. We also ruled out the
      possible effect of SUUR on histone genes expression and its involvement in DSB
      repair. CONCLUSIONS: Obtained results support the idea that SUUR protein
      contributes to the heterochromatin maintenance during the chromosome replication.
      A model that explains major SUUR-associated phenotypes is proposed.

PMID- 29191234
TI  - Analysis of the relationship between prescribed dose and dosimetric advantage of
      real-time intraoperatively built custom-linked seeds in iodine-125 prostate
      brachytherapy.
AB  - BACKGROUND: The purpose of this study was to investigate the differences in the
      dosimetric advantage of using intraoperatively built custom-linked (IBCL) seeds
      between permanent iodine-125 (I-125) seed implantation (PI) alone and PI followed
      by external-beam radiation therapy (EBRT) for prostate cancer. METHODS: We
      reviewed the records of 62 patients with localized prostate cancer who received
      transperineal interstitial brachytherapy with I-125 using free seeds or IBCL
      seeds. Twenty-four low- and intermediate-risk patients underwent PI alone with
      the prescribed dose of 160 Gy, and 39 high-risk patients underwent PI with 110
      Gy, followed by EBRT with 45 Gy (PI + EBRT). Intraoperative and post-implant
      dosimetric parameters 1 month after implantation were collected and analyzed.
      RESULTS: The numbers of patients implanted with free seeds and IBCL seeds were 14
      (58.3%) and 10 (41.7%), respectively, in the PI group and 25 (65.8%) and 13
      (34.2%), respectively, in the PI + EBRT group. In the PI group, although there
      were significant differences in prostate V100 (p = 0.003) and D90 (p = 0.009) and
      rectum V100 (p = 0.026) on intraoperative dosimetry, these differences were not
      found on post-implant dosimetry. In the PI + EBRT group, the dosimetric
      parameters of IBCL seeds, such as prostate V200 (p = 0.013) and V250 (p = 0.010)
      and urethra D30 (p = 0.038), were better than those of free seeds on
      intraoperative dosimetry. Furthermore, even on post-implant dosimetry, prostate
      D90 (p = 0.004), V150 (p = 0.001), and homogeneity index (HI, p = 0.001), as well
      as V200 (p = 0.001) and V250 (p = 0.020), and urethra D5 (p = 0.008) as well as
      D30 (p = 0.003) had a better dosimetric quality in IBCL seeds than in free seeds.
      There was no significant difference in the operation time between free seeds and
      IBCL seeds in each PI and PI + EBRT group. CONCLUSIONS: Our results reveal that
      greater dosimetric benefits could be obtained using IBCL seeds in the case of
      permanent implantation with a lower prescribed dose, such as PI + EBRT, rather
      than PI alone.

PMID- 29191235
TI  - Pediatric training and practice of Canadian chiropractic and naturopathic
      doctors: a 2004-2014 comparative study.
AB  - BACKGROUND: To assess chiropractic (DC) and naturopathic doctors' (ND) knowledge,
      attitudes, and behaviour with respect to the pediatric patients in their
      practice. METHODS: Cross-sectional surveys were developed in collaboration with
      DC and ND educators. Surveys were sent to randomly selected DCs and NDs in
      Ontario, Canada in 2004, and a national online survey was conducted in 2014. Data
      were analyzed using descriptive statistics, t-tests, non-parametric tests, and
      linear regression. RESULTS: Response rates for DCs were n = 172 (34%) in 2004, n
      = 553 (15.5%) in 2014, and for NDs, n = 171 (36%) in 2004, n = 162 (7%) in 2014.
      In 2014, 366 (78.4%) of DCs and 83 (61%) of NDs saw one or more pediatric
      patients per week. Pediatric training was rated as inadequate by most respondents
      in both 2004 and 2014, with most respondents (n = 643, 89.9%) seeking post
      graduate training by 2014. Respondents' comfort in treating children and youth is
      based on experience and post-graduate training. Both DCs and NDs that see
      children and youth in their practices address a broad array of pediatric health
      concerns, from well child care and preventative health, to mild and serious
      illness. CONCLUSIONS: Although the response rate in 2014 is low, the concerns
      identified a decade earlier remain. The majority of responding DCs and NDs see
      infants, children, and youth for a variety of health conditions and issues, but
      self-assess their undergraduate pediatric training as inadequate. We encourage
      augmented pediatric educational content be included as core curriculum for DCs
      and NDs and suggest collaboration with institutions/organizations with expertise
      in pediatric education to facilitate curriculum development, especially in areas
      that affect patient safety.

PMID- 29191236
TI  - A new methanogen "Methanobrevibacter massiliense" isolated in a case of severe
      periodontitis.
AB  - BACKGROUND: A few methanogens have been previously recovered from periodontitis
      lesions, yet their repertoire may not be completed. We recovered a previously
      unreported methanogen species in this situation. CASE PRESENTATION: A 64-year-old
      Caucasian woman was diagnosed with chronic, severe generalized periodontitis. In
      the presence of negative controls, an 18-month culture of periodontal pockets in
      anaerobe Hungate tube yielded "Methanobrevibacter massiliense" and Pyramidobacter
      piscolens. CONCLUSIONS: This case report provides evidence of the symbiotic
      strategy deployed by the methanogens and the anaerobes, and reports the first
      culture of a new methanogen, "M. massiliense".

PMID- 29191237
TI  - The immediate effect of a soft knee brace on pain, activity limitations, self
      reported knee instability, and self-reported knee confidence in patients with
      knee osteoarthritis.
AB  - BACKGROUND: We aimed to (i) evaluate the immediate effect of a soft knee brace on
      pain, activity limitations, self-reported knee instability, and self-reported
      knee confidence, and (ii) to assess the difference in effect between a non-tight
      and a tight soft brace in patients with knee osteoarthritis (OA). METHODS: Forty
      four patients with knee OA and self-reported knee instability participated in the
      single-session, laboratory, experimental study. A within-subject design was used,
      comparing a soft brace with no brace, and comparing a non-tight with a tight soft
      brace. The outcome measures were pain, self-reported knee instability and knee
      confidence during level and perturbed walking on the treadmill and activity
      limitations (10-m walk test and the get up and go (GUG) test). Linear mixed
      effect model analysis for continuous outcomes and logistic generalized estimating
      equations for categorical outcomes were used to evaluate the effect of wearing a
      soft brace. RESULTS: Wearing a soft brace significantly reduced pain during level
      walking (B - 0.60, P = 0.001) and perturbed walking (B - 0.80, P < 0.001),
      reduced the time to complete the 10-m walk (B - 0.23, P < 0.001) and the GUG
      tests (B - 0.23, P = 0.004), reduced self-reported knee instability during level
      walking (OR 0.41, P = 0.002) and perturbed walking (OR 0.36, P < 0.001), and
      reduced lack of confidence in the knees during level walking (OR 0.45, P < 0.001)
      and perturbed walking (OR 0.56, P < 0.001), compared with not wearing a soft
      brace. There was no difference in effects between a non-tight and tight brace,
      except for the 10-m walk test. Wearing a tight brace significantly reduced the
      time to complete the 10-m walk test in comparison with wearing a non-tight brace
      (B - 0.11, P = 0.03). CONCLUSION: The results of this study indicate that a soft
      brace is an efficacious intervention targeting pain, activity limitations, self
      reported knee instability, and knee confidence in the immediate term in patients
      with knee OA. Further studies are needed evaluating the mode of action based on
      exerted pressure, and on the generalization to functioning in daily life. TRIAL
      REGISTRATION: trialregister.nl, NTR6363 . Retrospectively registered on 15 May
      2017.

PMID- 29191238
TI  - Ethnopharmacological studies of indigenous plants in Kel village, Neelum Valley,
      Azad Kashmir, Pakistan.
AB  - BACKGROUND: This explorative study was undertaken for the first time in Kel
      village located in the Upper Neelum Valley, Azad Kashmir, Pakistan. The purpose
      was to document the indigenous knowledge of the native people used in the
      preparation of herbal medicines. METHODS: To get the data on traditional uses of
      medicinal plants, 20 informants were interviewed. Quantitative ethnobotanical
      indices, i.e., use value (UV), relative frequencies of citation (RFC), informant
      consensus factor (Fic), fidelity level (FL), data matrix ranking (DMR),
      preference ranking (PR), and jaccard index (JI), were calculated for the recorded
      medicinal plants. RESULTS: A total of 50 medicinal plants belonging to 33
      families used in 13 disease categories were documented. Leaves were the
      frequently used plant parts, and decoction was the commonly used method for
      herbal medicine. Plants with high use value were Berberis lycium (2.05),
      Impatiens glandulifera (1.95), Artemisia scoparia (1.75), Ageratum conozoides
      (1.75), and Achillea millefolium (1.7). The highest RFC value was calculated for
      Berberis lycium (0.75), Cynoglossum lanceolatum (0.65), and Impatiens
      glandulifera and Achillea millefolium (0.60 each). The maximum informant
      consensus factor was for urinary system, cardiac diseases, baldness, and abortion
      and miscarriage (1.00). Berberis lyceum (95%) used in jaundice, hepatitis,
      typhoid, fever, and tuberculosis disorders. Plants with maximum fidelity level
      (FL) were Berberis lycium (95%) followed by Dioscorea bulbifera, Impatiens
      glandulifera, and Artemisia vulgaris (90%). Olea ferruginea was the most
      multipurpose plant and exports (21.2%) was the leading threat in the area. The
      pearson correlation coefficient (0.500) showed a positive correlation between the
      use value and relative frequency of citation. CONCLUSION: The present study
      provides useful information about traditional uses of medicinal plants used by
      local communities in different ailments. The plants with the highest use values
      could be employed in pharmacological research and biotechnological approaches in
      order to achieve adequate revenue. Some of the plants in the study area are
      facing high threats of becoming rare, and conservation initiatives are needed to
      conserve them for sustainable management in the region.

PMID- 29191239
TI  - Fine-scale population genetic structure of arctic foxes (Vulpes lagopus) in the
      High Arctic.
AB  - OBJECTIVE: The arctic fox (Vulpes lagopus) is a circumpolar species inhabiting
      all accessible Arctic tundra habitats. The species forms a panmictic population
      over areas connected by sea ice, but recently, kin clustering and population
      differentiation were detected even in regions where sea ice was present. The
      purpose of this study was to examine the genetic structure of a population in the
      High Arctic using a robust panel of highly polymorphic microsatellites. RESULTS:
      We analyzed the genotypes of 210 individuals from Bylot Island, Nunavut, Canada,
      using 15 microsatellite loci. No pattern of isolation-by-distance was detected,
      but a spatial principal component analysis (sPCA) revealed the presence of
      genetic subdivisions. Overall, the sPCA revealed two spatially distinct genetic
      clusters corresponding to the northern and southern parts of the study area, plus
      another subdivision within each of these two clusters. The north-south genetic
      differentiation partly matched the distribution of a snow goose colony, which
      could reflect a preference for settling into familiar ecological environments.
      Secondary clusters may result from higher-order social structures
      (neighbourhoods) that use landscape features to delimit their borders. The
      cryptic genetic subdivisions found in our population may highlight ecological
      processes deserving further investigations in arctic foxes at larger, regional
      spatial scales.

PMID- 29191240
TI  - Myopia as a risk factor for subsequent retinal tears in the course of a
      symptomatic posterior vitreous detachment.
AB  - BACKGROUND: Retinal tears complicating the course of a posterior vitreous
      detachment (PVD) may be unique or multiple, and when multiple they may occur
      simultaneously or subsequently at different moments in the evolution of a PVD.
      The purpose of our study was to analyze the prevalence of subsequent retinal
      tears (SRT) in patients with a PVD, and to identify possible risk factors for
      SRT. METHODS: One hundred and seventy six eyes in 165 consecutive patients that
      presented one or more retinal tears in the evolution of a symptomatic PVD, with a
      minimum follow-up of 12 months, were retrospectively evaluated. The primary
      outcome measure was to characterize the clinical features associated with SRT
      formation against those eyes with non-subsequent retinal tear (NSRT-retinal
      tear/s diagnosed at initial examination) formation. For that purpose, this cohort
      of patients was divided into two different groups: group 1 included eyes
      presenting one or multiple retinal tears only at initial examination (NSRT), and
      group 2 eyes that progressed to a further retinal tear/s (SRT) during follow-up.
      RESULTS: Group 1 comprised 154 eyes from 145 patients, 48.7% males and 51.3%
      females with a mean age of 56.9 +/- 14.0 years (range = 15-89); 17.2% of patients
      had a previous retinal tear or retinal detachment in the fellow eye; mean number
      of retinal tears per eye 1.42 +/- 0.8 (range = 1-5); 20.8% presented bilateral
      retinal tears; 59.1% were myopic eyes (p < 0.05). Group 2 comprised 22 eyes from
      20 patients; mean age was 53.3 +/- 13.6 years (range = 30-69); 63.6% were male (p
      = 0.13), and 7 patients (31.8%) had a history of SRT or retinal detachment in the
      fellow eye (p = 0.13). The mean number of retinal tears per eye was 1.36 +/- 0.5
      (range = 1-2); bilateral retinal tears were noted in 18.2% of eyes; 86.4% were
      myopic eyes (p = 0.01); 81.8% occurred within a 120 days-period following
      diagnosis of the first retinal tear. CONCLUSIONS: Multiple retinal tears may be
      diagnosed in the evolution of a PVD. SRT are most frequently observed in myopic
      patients, and are usually symptomatic. Follow-up must extend for at least 4
      months after the initial symptoms.

PMID- 29191241
TI  - Preoperative detection of pleural adhesions by respiratory dynamic computed
      tomography.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) plays an important role in
      thoracic surgery because it is less invasive. However, the existence of severe
      pleural adhesions may make VATS difficult and complicated. The aim of this study
      was to assess the utility of inspiration and expiration computed tomography
      (respiratory dynamic CT (RD-CT)) in evaluation of pleural adhesions
      preoperatively. METHODS: RD-CT was performed on 107 patients undergoing
      thoracotomies (both VATS and open). We assessed synchronous motion during
      respiration on RD-CT. Comparing the results of RD-CT and intraoperative findings,
      we assessed the utility of preoperative evaluation. RESULTS: A negative
      correlation between sliding score and adhesion grade was revealed. Sliding score
      in adhesion negative patients was significantly higher than that in adhesion
      positive patients (P < 0.0001). The sensitivity of RD-CT was 63.6%, specificity
      was 74.1%, and accuracy was 72%. Among 62 patients with a CT-Respiration Ratio of
      less than 0.65, the sensitivity of RD-CT was 77.8%, specificity was 86.8%, and
      accuracy was 85.5%. CONCLUSIONS: RD-CT may be clinically useful for detecting the
      presence of pleural adhesions. It can be adopted as one of the criteria for
      deciding the surgical approach.

PMID- 29191243
TI  - Potential for broad-scale transmission of Ebola virus disease during the West
      Africa crisis: lessons for the Global Health security agenda.
AB  - BACKGROUND: The 2014-2016 Ebola crisis in West Africa had approximately eight
      times as many reported deaths as the sum of all previous Ebola outbreaks. The
      outbreak magnitude and occurrence of multiple Ebola cases in at least seven
      countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of
      broad-scale transmission of Ebola. MAIN TEXT: Using a modeling tool developed by
      the US Centers for Disease Control and Prevention during the Ebola outbreak, we
      estimated the number of Ebola cases that might have occurred had the disease
      spread beyond the three countries in West Africa to cities in other countries at
      high risk for disease transmission (based on late 2014 air travel patterns). We
      estimated Ebola cases in three scenarios: a delayed response, a Liberia-like
      response, and a fast response scenario. Based on our estimates of the number of
      Ebola cases that could have occurred had Ebola spread to other countries beyond
      the West African foci, we emphasize the need for improved levels of preparedness
      and response to public health threats, which is the goal of the Global Health
      Security Agenda. Our estimates suggest that Ebola could have potentially spread
      widely beyond the West Africa foci, had local and international health workers
      and organizations not committed to a major response effort. Our results
      underscore the importance of rapid detection and initiation of an effective,
      organized response, and the challenges faced by countries with limited public
      health systems. Actionable lessons for strengthening local public health systems
      in countries at high risk of disease transmission include increasing health
      personnel, bolstering primary and critical healthcare facilities, developing
      public health infrastructure (e.g. laboratory capacity), and improving disease
      surveillance. With stronger local public health systems infectious disease
      outbreaks would still occur, but their rapid escalation would be considerably
      less likely, minimizing the impact of public health threats such as Ebola.
      CONCLUSIONS: The Ebola outbreak could have potentially spread to other countries,
      where limited public health surveillance and response capabilities may have
      resulted in additional foci. Health security requires robust local health systems
      that can rapidly detect and effectively respond to an infectious disease
      outbreak.

PMID- 29191244
TI  - Frequency, characteristics and risk factors of QT interval prolonging drugs and
      drug-drug interactions in cancer patients: a multicenter study.
AB  - BACKGROUND: Cancer patients may receive a high number of medications with the
      potential to prolong QT interval and subsequent TdP (torsades de pointes). This
      study aimed to identify the prevalence of QT prolonging drugs, their TdP risk, QT
      prolonging drug-drug interactions (QT-DDIs), levels, predictors, and TdP risk of
      drugs involved in QT-DDIs. METHODS: This multicenter study included cancer
      patients from three major tertiary care hospitals of Khyber-Pakhtunkhwa,
      Pakistan. Micromedex DrugReax(r) was used for identification of QT-DDIs. TdP
      risks were identified by AZCERT (Arizona Center for Education and Research on
      Therapeutics) classification. Logistic regression analysis was performed to
      identify predictors of QT-DDIs. RESULTS: Of 555 patients, 51% were females. Mean
      age was 46.9 +/- 15.7 years. Total 28 distinct QT prolonging drugs were
      identified in 92.6% of the patients. Overall 21.8% patients were presented with
      QT-DDIs. Of total 288 identified QT-DDIs, all were of major-severity and fair
      documentation. According to AZCERT classification, 59.9% of the interacting drugs
      were included in list-1 (known risk of TdP), 4.7% in list-2 (possible risk of
      TdP) and 6.8% in list-3 (conditional risk of TdP). Univariate logistic regression
      analysis showed significant results for various predictors such as, 8-9
      prescribed medications (p < 0.001) and >=10 medications (p < 0.001), 2 QT drugs
      (p < 0.001) and >=3 QT drugs (p < 0.001), breast cancer (p = 0.03),
      gastrointestinal cancer (p = 0.03), 4-5 supportive care drugs (p < 0.001), 6-8
      supportive care drugs (p < 0.001) and >8 supportive care drugs (p < 0.001).
      CONCLUSIONS: A high prevalence of QT prolonging drugs and QT-DDIs was reported in
      oncology. Appropriate precautions are needed to prevent harmful consequences of
      these interactions.

PMID- 29191242
TI  - Copy number variation meta-analysis reveals a novel duplication at 9p24
      associated with multiple neurodevelopmental disorders.
AB  - BACKGROUND: Neurodevelopmental and neuropsychiatric disorders represent a wide
      spectrum of heterogeneous yet inter-related disease conditions. The overlapping
      clinical presentations of these diseases suggest a shared genetic etiology. We
      aim to identify shared structural variants spanning the spectrum of five
      neuropsychiatric disorders. METHODS: We investigated copy number variations
      (CNVs) in five cohorts, including schizophrenia (SCZ), bipolar disease (BD),
      autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD),
      and depression, from 7849 cases and 10,799 controls. CNVs were called based on
      intensity data from genome-wide SNP arrays and CNV frequency was compared between
      cases and controls in each disease cohort separately. Meta-analysis was performed
      via a gene-based approach. Quantitative PCR (qPCR) was employed to validate novel
      significant loci. RESULTS: In our meta-analysis, two genes containing CNVs with
      exonic overlap reached genome-wide significance threshold of meta P value < 9.4 *
      10-6 for deletions and 7.5 * 10-6 for duplications. We observed significant
      overlap between risk CNV loci across cohorts. In addition, we identified novel
      significant associations of DOCK8/KANK1 duplications (meta P value = 7.5 * 10-7)
      across all cohorts, and further validated the CNV region with qPCR. CONCLUSIONS:
      In the first large scale meta-analysis of CNVs across multiple
      neurodevelopmental/psychiatric diseases, we uncovered novel significant
      associations of structural variants in the locus of DOCK8/KANK1 shared by five
      diseases, suggesting common etiology of these clinically distinct
      neurodevelopmental conditions.

PMID- 29191245
TI  - 3.0T MRI for long-term observation of lung nodules post cryoablation: a pilot
      study.
AB  - BACKGROUND: The purpose of this study was to use serial magnetic resonance
      imaging (MRI) examinations to observe changes in malignant lung tumors over time
      post-cryoablation. METHODS: The study protocol was approved by Institutional
      Review Board, and written informed consent was obtained from each participant in
      accordance with the Declaration of Helsinki. Patients with primary or metastatic
      lung tumors eligible for cryoablation were included in this prospective study.
      Cryoablation was performed according to standard procedures. Unenhanced and
      dynamic contrast-enhanced MRI scans were performed pre-cryoablation and at 1 day,
      1 week, and 3-, 6-, and 12 months after cryoablation. At each time point, the
      signal intensity of the ablated zone on both T1WI and T2WI images, and volume and
      characteristics of the ablation zone were examined, and changes over time
      analyzed. RESULTS: A total of 26 nodules in 23 patients were included in the
      study. The mean patient age was 53.7 +/- 13.6 years, and 57.7% were males.
      Ablation zone volume increased to 1 week after the procedure, and then returned
      to baseline by 3 months. Cavitation post-cryoablation was found in 34.6% (9/26)
      of the nodules 1 month after treatment. Two types of time-signal intensity curves
      post-cryoablation were found: a straight line representing no definite
      enhancement from 1-day to 1-month, and an inflow curve representing mild delayed
      enhancement from month 3 to month 12. Local progression was associated with an
      incomplete hypointense rim around the ablation zone and absence of cavitation
      post-treatment. CONCLUSIONS: Characteristic changes are present on MRI after
      cryoablation of lung tumors. A complete hypointense rim and cavitation may be
      signs of adequate treatment and that local tumor progression is less likely.

PMID- 29191247
TI  - The implication of the shortage of health workforce specialist on universal
      health coverage in Kenya.
AB  - BACKGROUND: Globally, there is an acute shortage of human resources for health
      (HRH), and the greatest burden is borne by low-income countries especially in sub
      Saharan Africa and some parts of Asia. This shortage has not only considerably
      constrained the achievement of health-related development goals but also impeded
      accelerated progress towards universal health coverage (UHC). Like any other low
      income country, Kenya is experiencing health workforce shortage particularly in
      specialized healthcare workers to cater for the rapidly growing need for
      specialized health care (MOH Training Needs Assessment report (2015)). Efficient
      use of the existing health workforce including task shifting is under
      consideration as a short-term stop gap measure while deliberate efforts are being
      put on retention policies and increased production of HRH. METHODS: The Ministry
      of Health (MOH) with support from the United States Agency for International
      Development-funded FUNZOKenya project and MOH/Japan International Cooperation
      Agency (JICA) project conducted a country-wide training needs assessment (TNA) to
      identify skill gaps in the provision of specialized health care in private and
      public hospitals in 46 out of Kenya's 47 counties between April and June 2015. A
      total of 99 respondents participated in the TNA. Structured questionnaires were
      used to undertake this assessment. The assessment sought to determine the extent
      of skill gaps on the basis of the national guidelines and as perceived by the
      County Directors of Health (CDH). The questionnaires were posted to and received
      by all the respondents a week prior to a face-to-face interview with the
      respondents for familiarization. Data analysis was done using SPSS statistical
      package. RESULTS: Overall, the findings revealed average skill gaps on selected
      specialists (healthcare professional whose practice is limited to a particular
      area, such as a branch of medicine, surgery, or nursing, especially, one who by
      virtue of advanced training is certified by a specialty board as being qualified
      to so limit his or her practice, Free dictionary) at 85 and 62% when compared to
      the guideline and as perceived by the CDH respectively. It also revealed that
      gynecologists exceeded the requirements by 88 and 246% against the guidelines and
      as perceived by the CDH respectively. CONCLUSION: There is an overall huge gap in
      health specialists across the 46 counties, and the focus of training should be on
      the following specialists: cardio-surgeons, neurosurgeons, oncologists,
      nephrologists, lung and skin clinical officers, anesthetic clinical officers,
      cardiology nurses, forensic nurses, dental nurses, accident and emergency nurses,
      and oncology nurses. More innovative approaches, including the use of technology,
      need to be considered to address this challenge in the immediate, medium, and
      long terms. Policies and legal frameworks should be developed to facilitate cross
      county sharing of specialist expertise. Efforts need to be made to ensure
      harmonized skill gaps revealed by the guideline and as perceived by the CDHs to
      inform the development of mitigation strategies.

PMID- 29191246
TI  - MUNC18-1 gene abnormalities are involved in neurodevelopmental disorders through
      defective cortical architecture during brain development.
AB  - While Munc18-1 interacts with Syntaxin1 and controls the formation of soluble N
      ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex to
      regulate presynaptic vesicle fusion in developed neurons, this molecule is likely
      to be involved in brain development since its gene abnormalities cause early
      infantile epileptic encephalopathy with suppression-burst (Ohtahara syndrome),
      neonatal epileptic encephalopathy and other neurodevelopmental disorders. We thus
      analyzed physiological significance of Munc18-1 during cortical development.
      Munc18-1-knockdown impaired cortical neuron positioning during mouse
      corticogenesis. Time-lapse imaging revealed that the mispositioning was
      attributable to defects in radial migration in the intermediate zone and cortical
      plate. Notably, Syntaxin1A was critical for radial migration downstream of Munc18
      1. As for the underlying mechanism, Munc18-1-knockdown in cortical neurons
      hampered post-Golgi vesicle trafficking and subsequent vesicle fusion at the
      plasma membrane in vivo and in vitro, respectively. Notably, Syntaxin1A-silencing
      did not affect the post-Golgi vesicle trafficking. Taken together, Munc18-1 was
      suggested to regulate radial migration by modulating not only vesicle fusion at
      the plasma membrane to distribute various proteins on the cell surface for
      interaction with radial fibers, but also preceding vesicle transport from Golgi
      to the plasma membrane. Although knockdown experiments suggested that Syntaxin1A
      does not participate in the vesicle trafficking, it was supposed to regulate
      subsequent vesicle fusion under the control of Munc18-1. These observations may
      shed light on the mechanism governing radial migration of cortical neurons.
      Disruption of Munc18-1 function may result in the abnormal corticogenesis,
      leading to neurodevelopmental disorders with MUNC18-1 gene abnormalities.

PMID- 29191248
TI  - Squamous cell carcinoma arising from a keratocystic odontogenic tumor: a case
      report.
AB  - BACKGROUND: The term "primary intraosseous squamous cell carcinoma" was
      introduced in 2005 by the World Health Organization with three subcategories.
      Squamous cell carcinoma arising from the lining of an odontogenic cyst is one
      important rare subcategory of such lesions with an incidence of 0.01 to 0.02%.
      Furthermore, the appearance of such malignancy in an odontogenic tumor such as
      keratocystic odontogenic tumor is considered extremely rare. CASE PRESENTATION:
      In this case report we report a case of a 50-year-old Sri Lankan woman who
      complained of pain and increase in the size of a swelling at the anterior
      mandible, which had been present for over 1 year. The increase was significant
      for 1 month with accompanying numbness of the left half of her lip. Cone beam
      computed tomography results revealed an irregular radiolucent lesion involving
      most of her mandible and, except in the anterior part, very little buccolingual
      expansion was seen that suggested a keratocystic odontogenic tumor. An excision
      biopsy of the cyst lining confirmed a squamous cell carcinoma arising from a
      preexisting keratocystic odontogenic tumor. CONCLUSIONS: Even though primary
      intraosseous squamous cell carcinoma arising from a keratocystic odontogenic
      tumor is considered to be very rare, the present case is comparable to most of
      the aspects cited in the literature. The current case emphasizes the importance
      of careful investigation of swellings present in the mandible. Clinicians as well
      as patients should be aware and detect these changes to avoid being clinically
      negligent.

PMID- 29191249
TI  - Tracing GFP-labeled WJMSCs in vivo using a chronic salpingitis model: an animal
      experiment.
AB  - BACKGROUND: The present study was conducted to evaluate the distribution of
      Wharton's jelly-derived mesenchymal stem cells (WJMSCs) and their repairing
      function on the oviduct. METHODS: WJMSCs were transfected with the LV3-GFP-PURO
      lentivirus. Female New Zealand rabbits (n = 24) were divided randomly into
      control A and B groups and experimental C and D groups to establish inflammation
      models. Sterile saline solution or WJMSCs were injected into rabbits via ear
      veins and/or genital tract perfusion once weekly for 3 weeks. All rabbits were
      humanely sacrificed 1 week after the last perfusion to collect the oviduct,
      uterus, liver, and bladder for examination. Green fluorescent protein (GFP) and
      cytokeratin 7 (CK7) were imaged using a Leica Qwin Plus V3 fluorescence confocal
      microscope and analyzed as mean optical densities in an Image-Pro Plus analysis
      system. RESULTS: We found that lentivirus expressing the GFP gene produced an
      efficient transfection. The mean optical density values of GFP and CK7 in the
      oviducts were higher in the experimental D group than those in the control A and
      experimental C groups. No GFP fluorescence deposits occurred in the bladder of
      the control A group or experimental C group. Colocalization of CK7 and WJMSCs was
      observed in the oviducts in all groups. CONCLUSIONS: WJMSCs exhibited homing
      characteristics and migrated to the injured oviduct to promote epithelial cell
      growth. Additionally, local treatment resulted in higher efficiency.

PMID- 29191250
TI  - Sociodemographic factors are associated with dietary patterns in Mexican
      schoolchildren.
AB  - OBJECTIVE: Childhood obesity has increased rapidly in Mexico, along with changes
      in the food environment. However, little is known about the dietary patterns (DP)
      of Mexican children. We aimed to characterize the DP of schoolchildren and to
      analyse their associations with sociodemographic factors. DESIGN: Cross-sectional
      analysis. Dietary and sociodemographic information was obtained, including a
      single 24 h recall, socio-economic status (SES), geographic region, area of
      residence and ethnicity. DP were defined with cluster analysis (using k-means).
      Multinomial logistic regression models, adjusted for the survey design, were used
      to assess associations between DP and sociodemographic variables. SETTING: 2012
      Mexican National Health and Nutrition Survey (ENSANUT-2012). SUBJECTS:
      Schoolchildren (n 2751) aged 5-11 years who participated in ENSANUT-2012.
      RESULTS: Four DP were identified: 'Traditional', 'Industrialized', 'Varied' and
      'Modern'. Reported energy intake (mean (sd)) was lowest in the 'Traditional' and
      highest in the 'Industrialized' DP (7037 (3707) kJ/d (1682 (886) kcal/d) v. 8427
      (3753) kJ/d (2014 (897) kcal/d), respectively, P<0.05). Significant differences
      in fat and fibre intakes were seen across DP. Non-indigenous v. indigenous
      children were 22.0 times (95 % CI 5.1, 93.6) more likely to have a 'Modern'
      rather than 'Traditional' DP. Relative likelihood of having an 'Industrialized'
      rather than 'Traditional' DP was 6.2 (95 % CI 3.9, 9.9) among schoolchildren from
      high SES v. low SES. CONCLUSIONS: Among Mexican schoolchildren, DP were
      associated with sociodemographic variables. Non-indigenous children were
      significantly more likely to consume a 'Modern' than a 'Traditional' DP. Children
      with higher SES were more likely to have an 'Industrialized' pattern. It is
      necessary to consider dietary characteristics in the different sociodemographic
      strata when dietary interventions are designed.

PMID- 29191251
TI  - Grooves surrounding the micropyle decrease the inseminating dose in fish.
AB  - In fish with external fertilization, sperm must reach the oocyte through the
      micropyle to enter the cytoplasm. Fertilization success is then influenced by
      characteristics of oocytes or sperm. In this study, we evaluated oocyte
      morphology and sperm motility parameters and their effects on the inseminating
      dose in a teleost fish Astyanax altiparanae. Interestingly, we found one of the
      lowest yet described inseminating doses in teleosts (2390 spermatozoa oocyte-1 ml
      1). Such a fertilization efficacy may be explained by the long duration of sperm
      motility (>75 s), the small oocyte diameter (695.119 um), large micropyle
      diameter (7.57 um), and the presence of grooves on the oocyte surface that guides
      spermatozoon to the fertilization area. Additionally, we have described for the
      first time a structure that combines grooves on the chorion surface and a ridge
      in the micropylar area.

PMID- 29191252
TI  - Pseudopregnancy and aseasonal breeding in dairy goats: genetic basis of fertility
      and impact on lifetime productivity.
AB  - Until recently, the main selection focus in UK dairy goats has been on milk
      yield. To develop a selection index suitably weighted for a variety of traits, it
      is important to understand the genetic relationships between production, health
      and fertility traits. This study focussed on three aspects of reproduction that
      are of interest to goat breeders. (1) Out of season (OOS) kidding ability: goats
      are highly seasonal breeders so achieving consistent, year-round dairy production
      presents a challenge. It may be possible to select for extended or shifted
      breeding cycles, however, there are no published studies on the genetic basis of
      seasonal kidding ability, and a genetic correlation with milk production in dairy
      goats; (2) age at first kidding (AFK): a reduced AFK offers the opportunity for
      more rapid genetic improvement, as well as reducing the amount of time and
      resources required to raise the animals to producing age; (3) pseudopregnancy
      (PPG): as it is difficult to diagnose pregnancy within 30 days of mating, high
      herd levels of PPG could add a significant delay in breeding replacement animals,
      or commencing a new lactation. Using records from 9546 goats, the objective of
      this study was to investigate the genetic relationships between the reproductive
      traits described above, and the production traits 520-day milk yield (MY520),
      lifetime milk yield (MYLife) and lifetime number of days in milk (DIMLife). The
      'out of season' phenotype was defined as week of kidding relative to the 4 weeks
      of the year where the highest average number of births occur. Incidences of PPG
      that occurred during the first lactation were used as cases, while goats with
      none were assigned as controls. Relevant fixed and random effects were fitted in
      the models. In line with other reproduction traits, heritability estimates were
      low ranging from 0.08 to 0.11. A negative genetic correlation was found between
      AFK and MY520 (-0.22+/-0.10), whereas a positive genetic correlation was found
      between PPG and DIMLife (0.58+/-0.11). Pseudopregnancy and OOS were positively
      genetically correlated (0.36+/-0.15). All other genetic correlations were very
      low. The results of this study indicate that selection for the reproductive
      traits analysed is feasible, without adversely affecting MYLife.

PMID- 29191254
TI  - Characteristics of Medical Teams in Disaster.
AB  - Redmond AD . Characteristics of medical teams in disaster. Prehosp Disaster Med.
      2017:32(6):700.

PMID- 29191255
TI  - Resveratrol and inflammatory bowel disease: the evidence so far.
AB  - Despite the fact that inflammatory bowel disease (IBD) has still no recognised
      therapy, treatments which have proven at least mildly successful in improving IBD
      symptoms include anti-inflammatory drugs and monoclonal antibodies targeting pro
      inflammatory cytokines. Resveratrol, a natural (poly)phenol found in grapes, red
      wine, grape juice and several species of berries, has been shown to prevent and
      ameliorate intestinal inflammation. Here, we discuss the role of resveratrol in
      the improvement of inflammatory disorders involving the intestinal mucosa. The
      present review covers three specific aspects of resveratrol in the framework of
      inflammation: (i) its content in food; (ii) its intestinal absorption and
      metabolism; and (iii) its anti-inflammatory effects in the intestinal mucosa in
      vitro and in the very few in vivo studies present to date. Actually, if several
      studies have shown that resveratrol may down-regulate mediators of intestinal
      immunity in rodent models, only two groups have performed intervention studies in
      human subjects using resveratrol as an agent to improve IBD conditions. The
      effects of resveratrol should be further investigated by conducting well-designed
      clinical trials, also taking into account different formulations for the delivery
      of the bioactive compound.

PMID- 29191253
TI  - The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for
      structure-based drug design.
AB  - The apicomplexan protozoan parasites include the causative agents of animal and
      human diseases ranging from malaria (Plasmodium spp.) to toxoplasmosis
      (Toxoplasma gondii). The complex life cycle of T. gondii is regulated by a unique
      family of calcium-dependent protein kinases (CDPKs) that have become the target
      of intensive efforts to develop new therapeutics. In this review, we will
      summarize structure-based strategies, recent successes and future directions in
      the pursuit of specific and selective inhibitors of T. gondii CDPK1.

PMID- 29191256
TI  - Determination of Monensin in Bovine Tissues: A Bridging Study Comparing the
      Bioautographic Method (FSIS CLG-MON) with a Liquid Chromatography-Tandem Mass
      Spectrometry Method (OMA 2011.24).
AB  - The U.S. Department of Agriculture, Food Safety Inspection Service regulatory
      method for monensin, Chemistry Laboratory Guidebook CLG-MON, is a
      semiquantitative bioautographic method adopted in 1991. Official Method of
      AnalysisSM (OMA) 2011.24, a modern quantitative and confirmatory LC-tandem MS
      method, uses no chlorinated solvents and has several advantages, including ease
      of use, ready availability of reagents and materials, shorter run-time, and
      higher throughput than CLG-MON. Therefore, a bridging study was conducted to
      support the replacement of method CLG-MON with OMA 2011.24 for regulatory use.
      Using fortified bovine tissue samples, CLG-MON yielded accuracies of 80-120% in
      44 of the 56 samples tested (one sample had no result, six samples had accuracies
      of >120%, and five samples had accuracies of 40-160%), but the semiquantitative
      nature of CLG-MON prevented assessment of precision, whereas OMA 2011.24 had
      accuracies of 88-110% and RSDr of 0.00-15.6%. Incurred residue results
      corroborated these results, demonstrating improved accuracy (83.3-114%) and good
      precision (RSDr of 2.6-20.5%) for OMA 2011.24 compared with CLG-MON (accuracy
      generally within 80-150%, with exceptions). Furthermore, chi2 analysis revealed
      no statistically significant difference between the two methods. Thus, the
      microbiological activity of monensin correlated with the determination of
      monensin A in bovine tissues, and OMA 2011.24 provided improved accuracy and
      precision over CLG-MON.

PMID- 29191257
TI  - Proteasome Inhibitor MG132 Enhances Cisplatin-Induced Apoptosis in Osteosarcoma
      Cells and Inhibits Tumor Growth.
AB  - Although cisplatin has been shown to be an integral part of chemotherapy regimen
      in osteosarcoma (OS) treatment, toxicity issues and chemoresistance have hindered
      therapeutic development for OS. Exploring novel combination therapy methods is
      needed to circumvent the limitations of cisplatin alone. The proteasome inhibitor
      MG132 has shown antitumor effects in many solid tumors. However, little is known
      about its effects in combination with cisplatin in OS cells. In this study, we
      examined the effects of MG132 in combination with cisplatin in human OS cells (MG
      63 and HOS). MG132 and cisplatin were applied to OS cells, respectively or
      jointly. The results demonstrated that MG132 markedly inhibited cell viability in
      a dose- and time-dependent manner, whereas viability of osteoblast cells was not
      affected, suggesting a selective toxicity of MG132 to cancerous cells.
      Mechanistically, MG132 arrested cells in the G2/M phase in association with
      increased p21waf1 and induced cell apoptosis, which was accompanied by cleaved
      PARP. In addition to its apoptotic effect alone, MG132 significantly enhanced
      cisplatin-induced apoptosis in OS cells. Furthermore, cell viability of the
      combined application of 10 MUM MG132 and 5 MUg/ml cisplatin was markedly
      inhibited compared to that of the individual application. These events were
      accompanied by the downregulation of NF-kappaB, mitochondrial antiapoptotic
      protein Bcl-xL, and PI3K/Akt, which play a key role in cell survival. Finally,
      combination treatment of MG132 and cisplatin showed more antiproliferative effect
      than the single treatment in OS xenograft models. In summary, we concluded that
      MG132 interacted synergistically with cisplatin, which raised the possibility
      that combining the two drugs may represent a novel strategy in OS.

PMID- 29191258
TI  - Sun Smart Schools Nevada: Increasing Knowledge Among School Children About
      Ultraviolet Radiation.
AB  - BACKGROUND: Cumulative exposure to ultraviolet radiation (UV) is a risk factor
      for development of skin cancer. We estimated changes in knowledge, attitudes, and
      behaviors among Nevada school-age children following implementation of a program
      to decrease UV exposure. COMMUNITY CONTEXT: The Nevada Cancer Coalition's Sun
      Smart Schools pilot program was implemented in 7 Nevada schools during the 2015
      2016 school year. The target population was students at participating schools.
      METHODS: Participation in the program was voluntary. Students surveyed spanned
      grades from fourth to tenth. Pre-intervention surveys were conducted at the start
      of the school year. Post-intervention surveys were conducted at the end of the
      school year. Changes in knowledge, attitudes, and behaviors were assessed among
      study participants by using self-reported survey responses. OUTCOMES: The Sun
      Smart Schools pilot program was effective in increasing a broad range of
      knowledge, attitudes, and behaviors about protection from UV among elementary and
      middle school students. Students in high school reported an increase in the
      adoption of selected protective behaviors. However, this population also
      maintained a positive attitude toward the appearance of tanned skin, indicating
      susceptibility to competing influences. High school students also did not report
      any evident change in knowledge about sun protection strategies. Parents reported
      a decrease in knowledge about UV protection but an increase in adoption of
      certain protective behaviors. INTERPRETATION: Our findings are similar to those
      of previous studies demonstrating that education about the dangers of UV exposure
      is most effective in younger age groups. Results were mixed in older age groups.

PMID- 29191259
TI  - Exposure to Advertisements and Marijuana Use Among US Adolescents.
AB  - INTRODUCTION: This study examined whether exposure to marijuana advertisements
      was associated with current marijuana use and frequency of use among US
      adolescents in grades 8, 10, and 12. METHODS: Weighted estimates of exposure to
      marijuana advertisements and marijuana use from the 2014 and 2015 Monitoring the
      Future studies were investigated. Factors associated with the prevalence and
      frequency of marijuana use were analyzed by using logistic regression and linear
      regression models, respectively. RESULTS: Of all respondents (n = 12,988), 13.8%
      reported marijuana use in the past 30 days. Exposure to marijuana advertisements
      was prevalent among adolescents, with 52.8% reporting exposure from internet
      advertisements, 32.1% from television advertisements, 24.1% from magazine or
      newspaper advertisements, 19.7% from radio advertisements, 19.0% from
      advertisements on storefronts, and 16.6% from billboards. In the multivariable
      analysis, current use of marijuana among adolescents was associated with exposure
      to marijuana advertisements on storefronts (adjusted odds ratio [OR] = 1.4, P <
      .001), magazines or newspapers (adjusted OR = 1.6, P < .001), billboards
      (adjusted OR = 1.4, P = .002), internet (adjusted OR = 1.8, P < .001), television
      (adjusted OR = 1.4, P < .001) and radio (adjusted OR = 1.7, P < .001). Exposure
      to marijuana advertisements from the internet was associated with increased use
      of marijuana (beta = 0.3, P = .04). CONCLUSION: Exposure to marijuana
      advertisements was associated with higher odds of current marijuana use among
      adolescents. Regulations that limit marijuana advertisements to adolescents and
      educational campaigns on harmfulness of illicit marijuana use are needed.

PMID- 29191260
TI  - Physical Activity as a Vital Sign: A Systematic Review.
AB  - INTRODUCTION: Physical activity (PA) is strongly endorsed for managing chronic
      conditions, and a vital sign tool (indicator of general physical condition) could
      alert providers of inadequate PA to prompt counseling or referral. This
      systematic review examined the use, definitions, psychometric properties, and
      outcomes of brief PA instruments as vital sign measures, with attention primarily
      to studies focused on arthritis. METHODS: Electronic databases were searched for
      English-language literature from 1985 through 2016 using the terms PA, exercise,
      vital sign, exercise referral scheme, and exercise counseling. Of the 838
      articles identified for title and abstract review, 9 articles qualified for full
      text review and data extraction. RESULTS: Five brief PA measures were identified:
      Exercise Vital Sign (EVS), Physical Activity Vital Sign (PAVS), Speedy Nutrition
      and Physical Activity Assessment (SNAP), General Practice Physical Activity
      Questionnaire (GPPAQ), and Stanford Brief Activity Survey (SBAS). Studies
      focusing on arthritis were not found. Over 1.5 years of using EVS in a large
      hospital system, improvements occurred in relative weight loss among overweight
      patients and reduction in glycosylated hemoglobin among diabetic patients. On
      PAVS, moderate physical activity of 5 or more days per week versus fewer than 5
      days per week was associated with a lower body mass index (-2.90 kg/m2). Compared
      with accelerometer-defined physical activity, EVS was weakly correlated (r =
      0.27), had low sensitivity (27%-59%), and high specificity (74%-89%); SNAP showed
      weak agreement (kappa = 0.12); GPPAQ had moderate sensitivity (46%) and
      specificity (50%), and SBAS was weakly correlated (r = 0.10-0.28), had poor to
      moderate sensitivity (18%-67%), and had moderate specificity (58%-79%).
      CONCLUSION: Few studies have examined a brief physical activity tool as a vital
      sign measure. Initial investigations suggest the promise of these simple and
      quick assessment tools, and research is needed to test the effects of their use
      on chronic disease outcomes.

PMID- 29191261
TI  - Do Cancer-Related Fatigue and Physical Activity Vary by Age for Black Women With
      a History of Breast Cancer?
AB  - INTRODUCTION: Cancer-related fatigue (CRF) is the most uncomfortable symptom
      among women with a history of breast cancer. Black women are more likely than
      women of other racial/ethnic groups to have CRF risk factors, such as physical
      inactivity and obesity, yet CRF studies have not focused on black women. We
      conducted a cross-sectional analysis to assess CRF and physical activity among
      black women survivors of breast cancer. METHOD: In May and July of 2012, 267
      members (mean age, 54 y) of the Sisters Network, Inc, completed an online survey
      of sociodemographic characteristics, medical characteristics, and physical
      activity, and a fatigue instrument (the Functional Assessment of Chronic Illness
      Therapy [FACIT]). Multiple linear regression assessed fatigue and physical
      activity compliance (ie, 150 minutes of moderate to vigorous physical activity
      per week). RESULTS: Participants had an average FACIT score of 32.3, Fatigue was
      greater (P < .001) among the 56% of women not meeting physical activity
      guidelines. In multivariable analysis, correlates of fatigue showed that physical
      activity compliance (beta = 3.20, P < .001) and older age group (50-59 y: beta =
      3.98, P = .001; >=60 y,: beta = 3.76, P = .003) were associated with less
      fatigue. The interaction between age and fatigue was also significant: mean
      differences in fatigue by physical activity level were obvious only among women
      younger than 50 years. (P < .001). CONCLUSION: Physical activity compliance was
      associated with a lower level of fatigue. However, the effect of physical
      activity on fatigue may differ by age. Interventions aimed at curbing CRF in
      black women should consider age-appropriate strategies that can be integrated
      into existing lifestyles.

PMID- 29191262
TI  - Controlling Chronic Diseases Through Evidence-Based Decision Making: A Group
      Randomized Trial.
AB  - INTRODUCTION: Although practitioners in state health departments are ideally
      positioned to implement evidence-based interventions, few studies have examined
      how to build their capacity to do so. The objective of this study was to explore
      how to increase the use of evidence-based decision-making processes at both the
      individual and organization levels. METHODS: We conducted a 2-arm, group
      randomized trial with baseline data collection and follow-up at 18 to 24 months.
      Twelve state health departments were paired and randomly assigned to intervention
      or control condition. In the 6 intervention states, a multiday training on
      evidence-based decision making was conducted from March 2014 through March 2015
      along with a set of supplemental capacity-building activities. Individual-level
      outcomes were evidence-based decision making skills of public health
      practitioners; organization-level outcomes were access to research evidence and
      participatory decision making. Mixed analysis of covariance models was used to
      evaluate the intervention effect by accounting for the cluster randomized trial
      design. Analysis was performed from March through May 2017. RESULTS:
      Participation 18 to 24 months after initial training was 73.5%. In mixed models
      adjusted for participant and state characteristics, the intervention group
      improved significantly in the overall skill gap (P = .01) and in 6 skill areas.
      Among the 4 organizational variables, only access to evidence and skilled staff
      showed an intervention effect (P = .04). CONCLUSION: Tailored and active
      strategies are needed to build capacity at the individual and organization levels
      for evidence-based decision making. Our study suggests several dissemination
      interventions for consideration by leaders seeking to improve public health
      practice.

PMID- 29191263
TI  - Persistent and severe hypoglycemia associated with trimethoprim-sulfamethoxazole
      in a frail diabetic man on polypharmacy: A case report and literature review?.
AB  - OBJECTIVE: Trimethoprim-sulfamethoxazole (co-trimoxazole) is a commonly used
      broad-spectrum antibiotic, but it can be associated with potentially serious
      adverse effects, often not recognized by clinicians. This is a relevant problem
      in elderly patients, who are particularly susceptible to adverse drug reactions.
      Moreover, multiple medications taken by older people increase the risk for
      adverse drug reactions and drug-drug interactions. CASE REPORT: We report the
      case of an 85-year-old man with diabetes mellitus who attended the emergency room
      with severe hypoglycemia that persisted despite multiple intravenous bolus doses
      and continuous infusion of glucose. He needed hospital admission to stabilize
      glycemia. The patient, a nursing home resident, was being treated with co
      trimoxazole for an uncomplicated urinary tract infection, but was also taking
      multiple additional drugs for his co-morbidities. After co-trimoxazole was
      discontinued, plasma glucose levels slowly stabilized within the normal range. A
      diagnosis of prolonged and refractory hypoglycemia induced mainly by the
      antimicrobial agent was made, with additional contribution from multiple other
      drugs. No further episodes of hypoglycemia occurred during the next 6 months of
      follow-up. CONCLUSION: This case study illustrates once more the critical
      importance of prescription appropriateness in elderly patients with multiple
      morbidities in terms of type and dosage of drugs, in order to avoid serious
      adverse reactions.?.

PMID- 29191264
TI  - The effect of dezocine pretreatment on dexamethasone-induced perineal irritation.

PMID- 29191265
TI  - Dapaconazole versus ketoconazole in the treatment of interdigital tinea pedis.

PMID- 29191266
TI  - Assessment of UV spectrophotometry for determination of plasmid DNA concentration
      in vector preparations for human gene therapy products.
AB  - The European Pharmacopoeia (Ph. Eur.) general chapter 5.14. Gene transfer
      medicinal products for human use suggests the use of absorbance measurements at
      260 nm to determine the DNA concentration of plasmid vectors used for the
      preparation of gene therapy products for human use. An international
      collaborative study was organised by the European Directorate for the Quality of
      Medicines & HealthCare (EDQM) to confirm the suitability of UV spectrophotometry
      for the quantification of plasmid vectors used in gene therapy (GT). Three
      Official Medicine Control Laboratories (OMCLs of the European OMCL Network) and
      members of the OMCL Working Group for GT products took part in the study, in
      which various types of spectrophotometers were assessed using common test
      samples. Results of the study demonstrated that UV spectrophotometry can be
      considered suitable for the quantification of plasmid DNA in GT products
      regardless of the instrument used.

PMID- 29191267
TI  - Prevention and Early Detection of Pancreatic Cancer.
AB  - Preventing cancer has much to offer. Aside from plummeting health care costs, we
      might enjoy a healthier life free of cancer and chronic disease. Prevention
      requires the adoption of healthier choices and a moderate amount of exercise. The
      supporting evidence is observational, clinical, and partly common sense. Further
      investigations reveal several substances in a whole-food plant-based diet that
      have protective effects and an inhibitory effect on tumor development. For
      pancreatic cancer, the basis of cure remains a century old operation that rarely
      cures. With little to lose, prevention deserves center stage and additional
      studies.

PMID- 29191268
TI  - The Evolving Role of Radiation in Pancreatic Cancer.
AB  - Pancreatic cancer is an aggressive malignancy with a poor long-term survival and
      only mild improvement in outcomes over the past 30 years. Local failure remains a
      problem and radiation can help improve control. The role of radiation therapy in
      has been controversial and is still evolving. This article reviews the trials of
      pancreatic cancer and radiation in adjuvant, neoadjuvant, and unresectable
      lesions. The article reviews the impact and outcomes of evolving radiation
      technology.

PMID- 29191269
TI  - Nonoperative Ablation of Pancreatic Neoplasms.
AB  - Pancreatic cancer is a poor prognostic tumor and about 20% of patients are
      eligible for surgical resection at the time of diagnosis. Recently, minimally
      invasive procedures have provided promising results as a therapeutic option for
      locally advanced unresectable pancreatic cancer. In particular, high-intensity
      focused ultrasound is an emerging noninvasive thermally ablative procedure that
      may have a dominant role in the future. Although the clinical applications of
      minimally invasive therapies to pancreatic cancers are still in their infancy,
      the results at present are promising.

PMID- 29191270
TI  - Preoperative Evaluation of a Pancreas Mass: Diagnostic Options.
AB  - As modern abdominal imaging equipment advances, pancreatic lesion detection
      improves. Most of these lesions are incidental, and present a conundrum to the
      clinician and create great anxiety to the patient until a final diagnosis is
      made. For the practicing physician, the plethora of diagnostic options is
      overwhelming. The relevant question is, what is the most efficient algorithm to
      follow and to arrive at a timely and accurate diagnosis. This article presents a
      logical approach to the initial evaluation of a pancreatic lesion to get the most
      information possible with the least amount of testing, and to avoid duplicative
      measures.

PMID- 29191271
TI  - Incidental Intraductal Papillary Mucinous Neoplasm, Cystic or Premalignant
      Lesions of the Pancreas: The Case for Aggressive Management.
AB  - Incidental cystic intrapancreatic lesions are daily findings in abdominal
      radiology. The discovery of incidental pancreatic lesions is increasingly common
      with technologic diagnostic advancements. This article provides a perspective and
      guideline on the clinical management of incidental intraductal papillary mucinous
      neoplasms and cystic or premalignant lesions of the pancreas.

PMID- 29191272
TI  - Nonfunctioning Incidental Pancreatic Neuroendocrine Tumors: Who, When, and How to
      Treat?
AB  - Asymptomatic non-functioning pancreatic neuroendocrine tumors are indolent, slow
      growing tumors, and surveillance is safe and reasonable. Despite consensus, size
      may be less important than grade and Ki-67 when making decisions regarding
      optimal therapy. Plans to proceed with surveillance or surgical resection require
      a multidisciplinary approach and a shared decision making process with
      colleagues, patients, and families. Decisions should be based on tumor
      characteristics, patient morbidities, preferences, and risks. As molecular
      diagnostics evolve, preoperative acquisition of tissue samples may become even
      more critical in choosing between operative management and surveillance.

PMID- 29191273
TI  - Rare Tumors and Lesions of the Pancreas.
AB  - There are a few entities that account for most solid and cystic masses of the
      pancreas. The pancreas harbors a wide array of diseases, including
      adenocarcinoma, and its variants, such as anaplastic and adenosquamous carcinoma.
      Other neoplasms include acinar cell carcinoma, solid pseudopapillary tumor, and
      sarcomas. Benign lesions include hamartomas, hemangiomas, lymphangioma, and
      plasmacytoma. Isolated metastases include renal cell carcinoma, melanoma, and
      other carcinomas. Benign inflammatory conditions, such as autoimmune pancreatitis
      and groove pancreatitis can also mimic solid neoplasms of the pancreas.

PMID- 29191274
TI  - Ex Vivo Resection and Autotransplantation for Pancreatic Neoplasms.
AB  - There are several low-grade pancreatic tumors whose biology permits the use of
      aggressive surgery to achieve a curative resection. Tumors that are deemed
      unresectable by conventional techniques due to mesenteric vessel involvement may
      benefit from ex vivo tumor resection and autotransplantation to allow complete
      resection while minimizing ischemic organ injury. Despite the excellent oncologic
      outcomes when used for these neoplasms, the procedure carries substantial
      morbidity and a high complication rate. But for patients who were otherwise
      offered total enterectomy and allotransplantation or told that their tumor was
      unresectable, ex vivo resection may offer them a hope for cure.

PMID- 29191275
TI  - Screening of Patients at Risk for Familial Pancreatic Cancer: What Is Beneficial?
AB  - Family history is a significant risk factor for developing pancreatic cancer and
      this hereditary risk can be secondary to familial cancer predisposition
      syndromes, hereditary pancreatitis, or familial pancreatic cancer. Certain high
      risk individuals are recommended to undergo screening for pancreatic cancer with
      endoscopic ultrasound or MRI/magnetic resonance retrograde
      cholangiopancreatography because of the potential to identify and curatively
      resect precursor lesions. The management of suspicious lesions identified on
      screening high-risk individuals is also discussed.

PMID- 29191276
TI  - Preoperative Stenting for Benign and Malignant Periampullary Diseases:
      Unnecessary if Not Harmful.
AB  - Preoperative biliary drainage (PBD) is often performed in patients with jaundice
      with the presumption that it will decrease the risk of postoperative
      complications. PBD carries its own risk of complications and, therefore, has been
      controversial. Multiple randomized controlled trials and metaanalyses have shown
      that PBD has significantly increased overall complications compared with surgery
      alone. As such, the routine application of PBD should be avoided except in a
      subset of clinical situations. This is discussed in detail in this article.

PMID- 29191277
TI  - A Tale of 2 Techniques: Preoperative Biliary Drainage and Routine Surgical
      Drainage with Pancreaticoduodenectomy.
AB  - Preoperative drainage of an obstructed biliary tree before pancreaticoduodenal
      resection (PDR) and placement of intraabdominal drains following pancreatic
      resection have been suggested to be both unnecessary and associated with a higher
      complication rate. The evidence for and against that practice is presented and
      analyzed to highlight its risks and benefits. A selective approach on an
      individual basis for preoperative biliary decompression is advocated, based on
      multiple factors. Additionally, the evidence for routine use of surgical drains
      after PDR is critically reviewed and the rationale for routine drainage is made.

PMID- 29191278
TI  - Timing of Pancreatic Resection and Patient Outcomes: Is There a Difference?
AB  - Rates of long-term survival after treatment of pancreatic cancer remain low, in
      part because most patients are still treated with primary resection. This
      approach is often inadequate because of early local control failures, early
      manifestation of metastatic disease because of the unrecognized and untreated
      systemic component of this disease, and because half of patients never receive
      multimodal therapy. Preoperative therapy can be used to improve local control and
      treat the systemic nature of pancreatic cancer while also selecting for patients
      who benefit from a morbid operation. Preoperative therapy makes sense for most
      patients with this aggressive and deadly disease.

PMID- 29191279
TI  - Cancer of the Pancreas-Actual 5, 10, and 20+Year Survival: The Lucky and
      Fortunate Few.
AB  - Cancer of the pancreas (CaP) is a dismal, uncommon, systemic malignancy. This
      article updates an earlier experience of actual long-term survival of CaP in
      patients treated between 1991 to 2000, and reviews the literature. Survival is
      expressed as actual, not projected, survival.

PMID- 29191280
TI  - Rare, Uncommon, and Unusual Complications After Pancreaticoduodenal Resection.
AB  - Complications after pancreaticoduodenal resection occur in at least 30% of
      patients. Most are a direct result of an intraoperative event, dissection, or
      anastomoses which account for the most serious morbidities, sepsis,
      pseudoaneurysms, and hemorrhage. Rarely, complications are due to the systemic
      impact of the procedure even if the procedure itself was unremarkable. Rare
      systemic complications after PDR (Transfusion transmitted Babesiosis, pituitary
      apoplexy, and TRALI) and a number of uncommon and unusual other complications are
      discussed. Pancreaticoduodenal resection is a significant operation with serious
      consequences. Decisions on selection of candidates and safe operations should be
      thoughtful and always in surgeons' minds.

PMID- 29191281
TI  - Adjuvant or Neoadjuvant Therapy in the Treatment in Pancreatic Malignancies:
      Where Are We?
AB  - Since the advent of modern surgery for pancreatic cancer, clinicians have
      recognized this cancer's propensity to recur locally, metastasize, and cause
      death. Despite significant efforts to improve patient outcomes with better
      adjuvant therapy, only modest gains in survival have been observed. An
      alternative strategy of neoadjuvant therapy followed by surgery has the potential
      to improve patient selection and survival, and expand the pool of patients
      eligible for curative surgery. This article summarizes large, randomized trials
      of adjuvant therapy, explains the limitations imposed by up-front surgery, and
      suggests neoadjuvant therapy as a rational alternative to initial surgery and
      adjuvant therapy.

PMID- 29191282
TI  - Foreword.

PMID- 29191283
TI  - A Symposium on Pancreatic Cancer: Time for a Paradigm Shift. An Overview and
      Personal Reflections.

PMID- 29191284
TI  - Fibroblasts and extracellular matrix: Targeting and therapeutic tools in fibrosis
      and cancer.

PMID- 29191285
TI  - Effects of 3 Different Elastic Therapeutic Taping Methods on the Subacromial
      Joint Space.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of 3 different
      elastic therapeutic taping methods on the subacromial joint space in healthy
      adults. METHODS: Pre-/post-test laboratory study method was used in this study.
      Forty-eight healthy adults with no prior history of shoulder injury or surgery
      and no history of dominant shoulder pain in the past 6 months were enrolled in
      the study. Participants were placed into 3 groups (8 males and 8 females per
      group) on the basis of a consecutively assigned allocation design. A baseline
      measurement of the acromiohumeral distance (AHD) was taken by using diagnostic
      ultrasonography for every participant. On the basis of group assignment,
      participants were then taped according to the Kinesio Tape (Kinesio Tex Classic
      Tape) guidelines in one of 3 conditions: (1) taping of the supraspinatus from
      insertion to origin; (2) taping of the anterior and posterior deltoids from
      insertion to origin; and (3) a combination of both techniques. After a 5-minute
      wait period, the AHD was remeasured with the tape intervention in place, with
      each participant serving as his or her own control. RESULTS: Data analysis showed
      a statistically significant increase in AHD when using the taping technique over
      the anterior and posterior deltoids (Condition 2). The subacromial space
      increased in both males and females when the supraspinatus was taped from
      insertion to origin (Condition 1), but not at a statistically significant level.
      Condition 3, in which both taping techniques were used simultaneously, did not
      show an increase at a statistically significant level. CONCLUSIONS: The
      application of the Kinesio Tape from insertion to muscle origin of the
      supraspinatus or the anterior and posterior deltoid increased the subacromial
      joint space.

PMID- 29191286
TI  - The Validity and Reproducibility of the Flexicurve in the Evaluation of Cervical
      Spine Lordosis.
AB  - OBJECTIVE: The purpose of this study was to measure the validity and reliability
      of flexicurve measurements of cervical curvature in the sagittal plane in adults.
      METHODS: One hundred thirteen adults were assessed in the seated position with
      flexicurve radiographs. Two groups were measured: (1) the validity group (n =
      55), and (2) the reliability group (n = 58). Both groups were subdivided into 3
      subgroups according to body mass index: underweight, normal weight, and
      overweight. Radiographs were simultaneously taken with flexicurve molded on the
      cervical spine. Pearson's correlation and the root mean square error were used
      for the concurrent validity. The reliability of the flexicurve was assessed by 3
      raters using the intraclass correlation coefficient (ICC), the standard error of
      the measurement (SEM), and minimal detectable change (MDC). RESULTS: For the
      concurrent validity, a high correlation (r = 0.570, P < .001, root mean square
      error = 9.8 degrees ), and excellent results were obtained for intra-rater (ICC =
      0.771, P < .001, SEM = 4.4 degrees , MDC = 8.6 degrees ) and inter-rater (ICC =
      0.775, P < .001, SEM = 4.3 degrees , MDC = 8.5 degrees ) reliability. The
      subgroups had different results, whereas the underweight subgroup consistently
      had the best results. CONCLUSION: These findings suggest that the flexicurve can
      be a valid instrument for evaluating the curvature of the cervical spine in the
      sagittal plane in adults classified according to the body mass index as
      underweight and normal weight. Reliable measurements were provided for its use
      whether by the same or different raters. The flexicurve can be recommended for
      use both in clinical practice and in research settings as long as the suggested
      protocol is followed.

PMID- 29191288
TI  - Spinal Manipulative Therapy and Sports Performance Enhancement: A Systematic
      Review.
AB  - OBJECTIVE: The purpose of this study was to review the literature regarding the
      relationship between spinal manipulative therapy (SMT) and sports performance.
      METHODS: PubMed and Embase databases were searched for original studies published
      up to July 2016. Inclusion criteria were if SMT has been applied to athletes and
      if any sports performance-related outcome was measured. RESULTS: Of the 581
      potential studies, 7 clinical trials were selected. Most studies had adequate
      quality (>=6/11) when assessed by the PEDro scale. None of those studies assessed
      performance at an event or competition. Four studies revealed improvement in a
      sports performance test after SMT. Meta-analysis could not be performed because
      of the wide differences in methodologies, design, and outcomes measured. Spinal
      manipulative therapy influences a wide range of neurophysiological parameters
      that could be associated with sports performance. Of the 3 studies where SMT did
      not improve test performance, 2 used SMT not for therapeutic correction of a
      dysfunctional vertebral joint but to an arbitrary previously set joint.
      CONCLUSIONS: Although 4 of 7 studies showed that SMT improved sports performance
      tests, the evidence is still weak to support its use. Spinal manipulative therapy
      may be a promising approach for performance enhancement that should be
      investigated with more consistent methodologic designs.

PMID- 29191287
TI  - A Survey of the Scope of Chiropractic Practice in South Africa: 2015.
AB  - OBJECTIVES: The purpose of this study was to identify characteristics specific to
      the chiropractic profession in South Africa and compare them with those of other
      countries where similar surveys have been conducted. METHODS: This survey
      utilized a structured questionnaire designed to reflect chiropractic practice in
      South Africa. The questionnaire was made available online for completion by 714
      chiropractic practitioners who were registered with the Allied Health Professions
      Council of South Africa in 2015. Participation was both voluntary and anonymous.
      RESULTS: The response rate was 32%; of the respondents, 56% were males and 44%
      were females. The majority of the respondents had a master's degree in
      chiropractic. Most participants worked between 31 and 40 hours and saw fewer than
      50 patients per week, typically allocating 31 to 45 minutes for initial
      consultations and 16 to 30 minutes for follow-up visits. Participants saw more
      female patients than male patients, and most patients were between the ages of 31
      and 50 years. Patients typically presented to chiropractors during the acute
      phase, the primary complaint was low back and pelvic pain/injury without leg
      pain, and overuse/repetitive stress was reported as being the common etiology.
      Chiropractors have developed interprofessional referral relationships with
      general practitioners and massage therapists. CONCLUSIONS: Compared with similar
      survey analyses from Switzerland, the United Kingdom, and the United States, our
      findings showed overlap, but some characteristics were unique to the chiropractic
      profession in South Africa.

PMID- 29191289
TI  - Introduction: Current preterm birth prevention strategies, Part 2.

PMID- 29191290
TI  - New techniques in evaluation of the cervix.
AB  - The process of parturition is poorly understood, but the cervix clearly plays a
      key role. Because of this, recent research efforts have been directed at
      objective quantification of cervical remodeling. Investigation has focused on two
      basic areas: (1) quantification of tissue deformability and (2) presence,
      orientation, and/or concentration of microstructural components (e.g. collagen).
      Methods to quantify tissue deformability include strain elastography and shear
      wave elasticity imaging (SWEI). Methods to describe tissue microstructure include
      attenuation and backscatter. A single parameter is unlikely to describe the
      complexities of cervical remodeling, but combining related parameters should
      improve accuracy of cervical evaluation. This chapter reviews options for
      cervical tissue characterization.

PMID- 29191291
TI  - Tocolysis: Present and future treatment options.
AB  - In the United States, the generally accepted indication for tocolytic therapy
      centers on suppression of preterm labor. This may be in the form of preventative
      therapy with progesterone in women with prior spontaneous preterm birth or as an
      acute intervention to suppress established uterine contractions associated with
      cervical change occurring at less than 37 weeks gestation. This article seeks to
      apply this perspective to tocolytic therapy. Here, we provide a review of current
      tocolytic options and what the last decade of discovery has revealed about the
      regulation of myometrial excitability and quiescence. Moving forward, we must
      incorporate the emerging molecular data that is amassing in order to develop
      novel and effective tocolytic therapeutic options to prevent preterm labor and
      spontaneous preterm birth (sPTB).

PMID- 29191292
TI  - Long-term childhood outcomes after interventions for prevention and management of
      preterm birth.
AB  - Globally, preterm birth rates are rising and have a significant impact on
      neonatal morbidity and mortality. Preterm birth remains difficult to prevent and
      a number of strategies for preterm birth prevention (progesterone, cervical
      pessaries, cervical cerclage, tocolytics, and antibiotics) have been identified.
      While some of these show more promise, there is a paucity of evidence regarding
      the long-term effects of these strategies on childhood outcomes. Strategies used
      to improve the health of babies if born preterm, such as antenatal magnesium
      sulfate for fetal neuroprotection and antenatal corticosteroids for fetal lung
      maturation, show evidence of short-term benefit but lack large-scale follow-up
      data of long-term childhood outcomes. Future research on preterm birth
      interventions should include long-term follow-up of the children, ideally with
      similar outcome measures to allow for future meta-analyses.

PMID- 29191293
TI  - Cardiac Transplantation: Current Outcomes and Contemporary Controversies.
AB  - Despite advances in pharmacologic and device treatment of chronic heart failure,
      long-term morbidity and mortality remain high, and many patients progress to end
      stage heart failure. Over the last 5 decades, heart transplantation (HTx) has
      become the preferred therapy for select patients with end-stage heart disease.
      However, although HTx has become standard of care for the management of end-stage
      heart failure, challenges continue to exist. The number of patients with end
      stage heart failure is increasing, whereas the number of donor organs remains
      constant and a limiting factor in HTx. Not only are there more potential heart
      transplantation candidates, but HTx candidates today are more complex: older,
      sensitized, and in need of mechanical circulatory support. Such candidates are at
      higher risk for poor outcomes including primary graft dysfunction and antibody
      mediated rejection. This article focuses on current post-transplantation outcomes
      and recent advances in HTx that could address the current challenges. These
      advances include: 1) attempts to expand the donor pool; 2) proposed changes in
      HTx allocation policy for more equitable organ distribution; 3) a better
      understanding of the definition and management of primary graft dysfunction; and
      4) advances in the management of sensitized HTx candidates. Developments in these
      areas could result in expansion and more equitable distribution of the donor pool
      and improved survival and quality of life for HTx recipients.

PMID- 29191294
TI  - Evolving Areas in Heart Transplantation.
AB  - It has been 50 years since Dr. Christiaan Barnard performed the first human-to
      human heart transplant in December 1967 in South Africa. Remarkable progress has
      been made since that time, including changes in surgical techniques,
      immunosuppression, donor and recipient selection, and post-transplant care. In
      this paper, we provide a perspective on the changing face of heart
      transplantation and highlight key evolving areas. Topics that are covered include
      advances in immunosuppression, screening for acute and chronic rejection, cardiac
      allograft vasculopathy, and ongoing advancements in cardiac replacement therapy,
      including xenotransplantation, stem-cell research, tissue engineering, and the
      total artificial heart.

PMID- 29191296
TI  - Cardiac Allograft Vasculopathy: It Really Has Changed Over Time.

PMID- 29191295
TI  - Changes in Outcomes of Cardiac Allograft Vasculopathy Over 30 Years Following
      Heart Transplantation.
AB  - OBJECTIVES: This study investigated temporal changes in the demographics and the
      prognosis of cardiac allograft vasculopathy (CAV) over 30 years following heart
      transplantation (HTx). BACKGROUND: Effects of the changing HTx demographics on
      CAV outcomes, based on International Society for Heart and Lung Transplantation
      (ISHLT) classification of CAV, have been incompletely investigated. METHODS:
      Patients who underwent HTx at the Montreal Heart Institute were classified
      according to the severity of CAV (CAV 0 is no presence of CAV; CAV 1 is mild, CAV
      2 to 3 is moderate to severe) and era of HTx (early: 1983 to 1998; recent: 1999
      to 2011). We compared the risk of progression, survival, and independent
      predictors of outcomes among the groups. RESULTS: A total of 298 patients were
      followed for 11.6 +/- 6.6 years. Patients who received transplants in the early
      era exhibited a higher risk for progression from CAV 1 to a higher grade
      (adjusted odds ratio: 8.0; 95% confidence interval [CI]: 1.01 to 62.6). The
      presence of CAV was associated with a significantly increased risk for all-cause
      mortality in the early era (hazard ratio [HR]: 1.6; 95% CI: 1.1 to 2.5) but not
      in the recent era (HR: 1.1; 95% CI: 0.2 to 4.9). Regardless of the era, CAV
      classes 2 to 3 and CAV 1 were associated with a significantly increased risk for
      all-cause mortality compared to CAV 0 (HR: 6.5; 95% CI: 2.7 to 15.7; and HR:
      1.750; 95% CI: 1.001 to 3.046, respectively). CONCLUSIONS: The progression and
      prognosis of CAV have improved over 30 years. The ISHLT CAV classification
      accurately and independently predicts long-term outcome following HTx.

PMID- 29191297
TI  - Verification of Heart Disease: Implications for a New Heart Transplantation
      Allocation System.
AB  - OBJECTIVES: This study sought to determine the accuracy of the pre
      transplantation clinical diagnosis of heart disease in the United Network for
      Organ Sharing (UNOS) database. BACKGROUND: Because survival on the heart
      transplantation waitlist depends on underlying heart disease, a new allocation
      system will include the type of heart disease. Accuracy of the pre
      transplantation clinical diagnosis and the effect of misclassification are
      unknown. METHODS: We included all adults who received transplants at our center
      between January 2009 to December 2015. We compared the pre-transplantation
      clinical diagnosis at listing with pathology of the explanted heart and
      determined the potential effect of misclassification with the proposed allocation
      system. RESULTS: A total of 334 patients had the following clinical cardiac
      diagnoses at listing: 148 had dilated cardiomyopathy, 19 had restrictive
      cardiomyopathy, 103 had ischemic cardiomyopathy, 24 had hypertrophic
      cardiomyopathy, 11 had valvular disease, 16 had congenital heart disease (CHD),
      and 13 patients had a diagnosis of "other." Pathology of the explanted hearts
      revealed 82% concordance and 18% discordance (10% coding errors and 8% incorrect
      diagnosis). The most common incorrect diagnoses were sarcoidosis (66%),
      arrhythmogenic right ventricular dysplasia (60%), and other causes of
      predominately right-sided heart failure (33%). Among the misclassified diagnoses,
      40% were listed as UNOS status 2, 8% remained at status 2 at transplantation, and
      only sarcoidosis and CHD were potentially at a disadvantage with the new
      allocation. CONCLUSIONS: There is high concordance between clinical and
      pathologic diagnosis, except for sarcoidosis and genetic diseases. Few
      misclassifications result in disadvantages to patients based on the new
      allocation system, but rare diseases like sarcoidosis remain problematic. To
      improve the UNOS database and enhance outcome research, pathology of the
      explanted hearts should be required post-transplantation.

PMID- 29191298
TI  - Demanding Truth in a Complex Heart Allocation System.

PMID- 29191300
TI  - Implantable Cardioverter-Defibrillators in Patients With Left Ventricular Assist
      Devices: On Trial and in Need of a Trial.

PMID- 29191299
TI  - Implantable Cardioverter-Defibrillators in Patients With a Continuous-Flow Left
      Ventricular Assist Device: An Analysis of the INTERMACS Registry.
AB  - OBJECTIVES: This study sought to determine if the presence of implantable
      cardioverter-defibrillators (ICD) provided a mortality benefit during continuous
      flow left ventricular assist device (LVAD) support. BACKGROUND: An ICD decreases
      mortality in selected patients with advanced heart failure and have been
      associated with reduced mortality in patients with pulsatile LVAD. However, it is
      unclear whether that benefit extends to patients with a contemporary continuous
      flow LVAD. METHODS: Propensity score matching was used to generate a cohort of
      patients with similar baseline characteristics. The primary outcome was freedom
      from death during LVAD support. Secondary endpoints included freedom from
      unexpected death, likelihood of transplantation and recovery, and adverse events.
      RESULTS: Among 16,384 eligible patients in the Interagency Registry for
      Mechanically Assisted Circulatory Support registry, 2,209 patients with an ICD
      and 2,209 patients without one had similar propensity scores and were included.
      The presence of an ICD was associated with an increased mortality risk (hazard
      ratio: 1.20; 95% confidence interval [CI]: 1.04 to 1.39; p = 0.013) and an
      increased risk of unexpected death during device support (HR: 1.33; 95% CI: 1.03
      to 1.71; p = 0.03). Patients with an ICD were more likely to undergo
      transplantation (HR: 1.16; 95% CI: 0.99 to 1.35; p = 0.06) and less likely to
      have LVAD explant for recovery (HR: 0.53, 95% CI: 0.29 to 0.98; p = 0.04).
      Patients with an ICD had a higher rate of treated ventricular arrhythmias (rate
      ratio: 1.27; 95% CI: 1.10 to 1.48; p = 0.001) and rehospitalization (rate ratio:
      1.08; 95% CI: 1.04 to 1.12; p < 0.0001), but rates of hemorrhagic stroke were
      similar (rate ratio: 1.01; 95% CI: 0.81 to 1.26; p = 0.98). CONCLUSIONS: Among
      patients with a continuous flow LVAD, the presence of an ICD was not associated
      with reduced mortality.

PMID- 29191301
TI  - Incremental Value of Deformation Imaging and Hemodynamics Following Heart
      Transplantation: Insights From Graft Function Profiling.
AB  - OBJECTIVES: This study investigated to define graft dysfunction and to determine
      its incremental association with long-term outcome after heart transplantation
      (HT). BACKGROUND: Although graft failure is an established cause of late
      mortality after HT, few studies have analyzed the prognostic value of graft
      dysfunction at 1- and 5-year follow-up of HT. METHODS: Patients who underwent HT
      and completed their first annual evaluation with right heart catheterization and
      echocardiography at Stanford University between January 1999 and December 2011
      were included in the study. Hierarchical clustering was used to identify modules
      to capture independent features of graft dysfunction at 1 year. The primary
      endpoint for analysis consisted of the composite of cardiovascular mortality, re
      transplantation, or heart failure hospitalization within 5 years of HT. The study
      further explored whether changes in graft dysfunction between 1 and 5 years were
      associated with 10-year all-cause mortality. RESULTS: A total of 215 HT
      recipients were included in the study. Using hierarchical clustering, 3
      functional modules were identified; among them, left ventricular global
      longitudinal strain (LVGLS), stroke volume index, and right atrial pressure (RAP)
      or pulmonary capillary wedge pressure (PCWP) captured key features of graft
      function. Graft dysfunction based on pre defined LVGLS in absolute value <14%,
      stroke volume index <35 ml/m2, RAP >10 mm Hg, or PCWP >15 mm Hg were present in
      41%, 36%, and 27%, respectively. The primary endpoint at 5 years occurred in 52
      patients (24%), whereas 10-year all-cause mortality occurred in 30 (27%) of 110
      patients alive at 5 years. On multivariate analysis, RAP (standardized hazard
      ratio: 1.63), LVGLS (standardized hazard ratio: 1.39), and a history of
      hemodynamically compromising rejection within 1 year (hazard ratio: 2.18) were
      independent predictors of 5-year outcome. RAP at 5 years, as well as change in
      RAP from 1 to 5 years, was predictive of 10-year all-cause mortality.
      CONCLUSIONS: RAP and LVGLS at the first annual evaluation provide complementary
      prognostic information in predicting 5-year outcome after HT.

PMID- 29191302
TI  - Are Neurogenic Stress Cardiomyopathy and Takotsubo Different Syndromes With
      Common Pathways?: Etiopathological Insights on Dysfunctional Hearts.

PMID- 29191304
TI  - Happy 50th Birthday, Cardiac Transplantation: Happy 5th Birthday, JACC: Heart
      Failure.

PMID- 29191305
TI  - Correction.

PMID- 29191303
TI  - Older and Wiser: Personalized Immunosuppression in the Current Era.

PMID- 29191306
TI  - [How can we improve the care of paediatric trauma?]

PMID- 29191307
TI  - Emerging Chemicals of Concern: Preface.

PMID- 29191308
TI  - Amoxicillin effects on functional microbial community and spread of antibiotic
      resistance genes in amoxicillin manufacture wastewater treatment system.
AB  - This study aimed to reveal how amoxicillin (AMX) affected the microbial community
      and the spread mechanism of antibiotic resistance genes (ARGs) in the AMX
      manufacture wastewater treatment system. For this purpose, a 1.47 L expanded
      granular sludge bed (EGSB) reactor was designed and run for 241days treating
      artificial AMX manufacture wastewater. 454 pyrosequencing was applied to analyze
      functional microorganisms in the system. The antibiotic genes OXA-1, OXA-2, OXA
      10, TEM-1, CTX-M-1, class I integrons (intI1) and 16S rRNA genes were also
      examined in sludge samples. The results showed that the genera Ignavibacterium,
      Phocoenobacter, Spirochaeta, Aminobacterium and Cloacibacillus contributed to the
      degradation of different organic compounds (such as various sugars and amines).
      And the relative quantification of each beta-lactam resistance gene in the study
      was changed with the increasing of AMX concentration. Furthermore the vertical
      gene transfer was the main driver for the spread of ARGs rather than horizontal
      transfer pathways in the system.

PMID- 29191309
TI  - Arsenic biotransformation and an arsenite S-adenosylmethionine methyltransferase
      in plankton.

PMID- 29191310
TI  - Dietary exposure to di-isobutyl phthalate increases urinary 5-methyl-2'
      deoxycytidine level and affects reproductive function in adult male mice.
AB  - Phthalates are a large family of ubiquitous environmental pollutants suspected of
      being endocrine disruptors. Epidemiological studies have associated phthalate
      metabolites with decreased reproductive parameters and linked phthalate exposure
      with the level of urinary 5-methyl-2'-deoxycytidine (5mdC, a product of
      methylated DNA). In this study, adult male mice were exposed to 450mg di-isobutyl
      phthalate (DiBP)/(kg.day) via dietary exposure for 28days. Mono-isobutyl
      phthalate (MiBP, the urinary metabolite) and reproductive function parameters
      were determined. The levels of 5mdC and 5-hydroxymethyl-2'-deoxycytidine (5hmdC)
      were measured in urine to evaluate if their contents were also altered by DiBP
      exposure in this animal model. Results showed that DiBP exposure led to a
      significant increase in the urinary 5mdC level and significant decreases in sperm
      concentration and motility in the epididymis, accompanied with reduced
      testosterone levels and down-regulation of the P450 cholesterol side-chain
      cleavage enzyme (P450scc) gene in the mice testes. Our findings indicated that
      exposure to DiBP increased the urinary 5mdC levels, which supported our recent
      epidemiological study about the associations of urinary 5mdC with phthalate
      exposure in the male human population. In addition, DiBP exposure impaired male
      reproductive function, possibly by disturbing testosterone levels; P450scc might
      be a major steroidogenic enzyme targeted by DiBP or other phthalates.

PMID- 29191311
TI  - Analysis of PFAAs in American alligators part 1: Concentrations in alligators
      harvested for consumption during South Carolina public hunts.
AB  - Environmental contamination resulting from the production or release of harmful
      chemicals can lead to negative consequences for wildlife and human health.
      Perfluorinated alkyl acids (PFAAs) were historically produced as protective
      coatings for many household items and currently persist in the environment,
      wildlife, and humans. PFAAs have been linked to immune suppression, endocrine
      disruption, and developmental toxicity in wildlife and laboratory studies. This
      study examines the American alligator, Alligator mississippiensis, as an
      important indicator of ecosystem contamination and a potential pathway for PFAA
      exposure in humans. Alligator meat harvested in the 2015 South Carolina (SC)
      public hunt season and prepared for human consumption was collected and analyzed
      for PFAAs to determine meat concentrations and relationships with animal body
      size (total length), sex, and location of harvest. Of the 15 PFAAs analyzed,
      perfluorooctane sulfonate (PFOS) was found in all alligator meat samples and at
      the highest concentrations (median 6.73ng/g). No relationship was found between
      PFAA concentrations and total length or sex. Concentrations of one or all
      compounds varied significantly across sampling locations, with alligators
      harvested in the Middle Coastal hunt unit having the highest PFOS concentrations
      (median 16.0ng/g; p=0.0001). Alligators harvested specifically from Berkley
      County, SC (located in the Middle Coastal hunt unit) had the highest PFOS
      concentrations and the greatest number of PFAAs detected (p<0.0001). The site
      specific nature of PFAA concentrations in alligator meat observed in this study
      suggests a source of PFAA contamination in Berkley County, SC.

PMID- 29191312
TI  - Enhanced ozonation degradation of atrazine in the presence of nano-ZnO:
      Performance, kinetics and effects.
AB  - Enhanced ozonation degradation of atrazine (ATZ) with nano-ZnO (nZnO) as catalyst
      and the influences of the operational parameters have been investigated through
      semi-continuous experiments in this study. The results demonstrated that the
      combination of ozone (O3) and nZnO showed an obvious synergetic effect and the
      ATZ degradation conformed to pseudo-first-order kinetics. An improvement of ATZ
      degradation efficiency by 41.8% and pseudo-first-order rate constant by more than
      a factor of four was obtained in the O3/nZnO process after 5min of reaction
      compared to O3 alone. Meanwhile, the degradation efficiency of ATZ was gradually
      enhanced with increasing nZnO dosage and initial pH in the range from 3.0 to 8.0,
      and a higher amount of ATZ was degraded when the initial concentration of ATZ
      rose from 0.5 to 5mg/L. Additionally, sulfate ion, chloride ion, nitrate ion and
      low concentrations of humic acid substances led to enhancement of the ATZ
      degradation. The notable decrease of ATZ removal efficiency observed in the
      presence of radical scavengers and the results of free radical tests indicated
      that OH is the dominant active radical species. The mechanism investigation
      demonstrated that the enhancement effect could be attributed to the introduction
      of nZnO, which could promote the utilization of O3, enhance the formation of
      superoxide radical, and further accelerate the production of hydrogen peroxide
      and the generation of OH/O2-.

PMID- 29191313
TI  - Analysis of PFAAs in American alligators part 2: Potential dietary exposure of
      South Carolina hunters from recreationally harvested alligator meat.
AB  - Exposure to perfluorinated alkyl acids (PFAAs) has been linked to many harmful
      health effects including reproductive disorders, developmental delays, and
      altered liver and kidney function. Most human exposure to environmental
      contaminants, including PFAAs, occurs through consumption of contaminated food or
      drinking water. This study uses PFAA data from meat samples collected from
      recreationally harvested American alligators (Alligator mississippiensis) in
      South Carolina to assess potential dietary exposure of hunters and their families
      to PFAAs. Consumption patterns were investigated using intercept surveys of 23
      hunters at a wild game meat processor. An exposure scenario using the average
      consumption frequency, portion size, and median perfluorooctane sulfonic acid
      (PFOS) concentration in alligator meat from all hunt units found the daily
      dietary exposure to be 2.11ng/kg body weight per day for an adult human. Dietary
      PFOS exposure scenarios based on location of harvest suggested the highest daily
      exposure occurs with alligator meat from the Middle Coastal hunt unit in South
      Carolina. Although no samples were found to exceed the recommended threshold for
      no consumption of PFOS found in Minnesota state guidelines, exposure to a mixture
      of PFAAs found in alligator meat and site-specific exposures based on harvest
      location should be considered in determining an appropriate guideline for
      vulnerable populations potentially exposed to PFAAs through consumption of wild
      alligator meat.

PMID- 29191314
TI  - Biodegradation of tetrabromobisphenol A in the sewage sludge process.
AB  - Anaerobic sewage sludge capable of rapidly degrading tetrabromobisphenol A
      (TBBPA) was successfully acclimated in an anaerobic reactor over 280days. During
      the period from 0 to 280days, the TBBPA degradation rate (DR), utilization of
      glucose, and VSS were monitored continuously. After 280days of acclimation, the
      TBBPA DR of active sludge reached 96.0% after 20days of treatment in batch
      experiments. Based on scanning electron microscopy (SEM) observations and
      denaturing gradient gel electrophoresis (DGGE) determinations, the diversity of
      the microorganisms after 0 and 280days in the acclimated anaerobic sewage sludge
      was compared. Furthermore, eleven metabolites, including 2-bromophenol, 3
      bromophenol, 2,4-dibromophenol, 2,6-dibromophenol, tribromophenol and bisphenol
      A, were identified by gas chromatography-mass spectrometry (GC-MS). Moreover, the
      six primary intermediary metabolites were also well-degraded by the acclimated
      anaerobic sewage sludge to varying degrees. Among the six target metabolites,
      tribromophenol was the most preferred substrate for biodegradation via
      debromination. These metabolites degraded more rapidly than monobromide and
      bisphenol A. The biodegradation data of the intermediary metabolites exhibited a
      good fit to a pseudo-first-order model. Finally, based on the metabolites,
      metabolic pathways were proposed. In conclusion, the acclimated microbial
      consortia degraded TBBPA and its metabolites well under anaerobic conditions.

PMID- 29191315
TI  - Occurrence and fate of endogenous steroid hormones, alkylphenol ethoxylates,
      bisphenol A and phthalates in municipal sewage treatment systems.
AB  - Steroid hormones, alkylphenol ethoxylates (APEOs) and phthalic acid esters (PAEs)
      are emerging endocrine disrupting chemicals (EDCs) that can interfere with the
      endocrine function in organisms at low concentrations. The occurrence,
      distribution behavior, removal rate and the fate of 31 target EDCs in sewage
      treatment plants, which consist of various treatment facilities and receiving
      water in Hong Kong, were investigated. Estrone, nonylphenol-di-ethoxylate and
      diethyl phthalate were found to be dominant in each group of influent samples
      with concentrations ranging from 11-33, 747-3945 and 445-4635ng/L, respectively.
      Conversely, progesterone, nonylphenol-mono-ethoxylate and bis (2-ethylhexyl)
      phthalate were the most abundant in dewatered sludge, with concentrations ranging
      from 0.9-237, 75-19,743 and 4310-37,016ng/g (dry weight). The removal rates of
      primary sedimentation and disinfection approaches were lower than 30% for most of
      the chemicals, while those of activated sludge and reverse osmosis were greater
      than 80% for more than two-thirds of the compounds, noticeably decreasing the
      estrogenic risk of sewage discharged into the environment. Steroid hormones were
      removed via biological degradation, while some APEOs and PAEs adsorbed to the
      sludge. Victoria Harbor poses a low to medium estrogenic risk mainly contributed
      by estrone and estradiol and deserves attention.

PMID- 29191316
TI  - Tissue distribution of perfluoroalkyl acids and health status in wild Mozambique
      tilapia (Oreochromis mossambicus) from Loskop Dam, Mpumalanga, South Africa.
AB  - This study examined concentrations of 15 perfluoroalkyl acids (PFAAs) in tissues
      from male Mozambique tilapia (Oreochromis mossambicus) collected at Loskop Dam,
      Mpumalanga, South Africa in 2014 and 2016. Nine of the 15 PFAAs were detected
      frequently and were included in statistical analysis and included two of the most
      commonly known PFAAs, perfluorooctanesulfonic acid (PFOS) (median, 41.6ng/g) and
      perfluorooctanoic acid (PFOA) (median, 0.0825ng/g). Of the tissues measured,
      plasma (2016 and 2014 median, 22.2ng/g) contained the highest PFAA burden
      followed by (in descending order): liver (median, 11.6ng/g), kidney (median,
      9.04ng/g), spleen (median, 5.92ng/g), adipose (median, 2.54ng/g), and muscle
      (median, 1.11ng/g). Loskop Dam tilapia have been affected by an inflammatory
      disease of the adipose tissue known as pansteatitis, so this study also aimed to
      investigate relationships between PFAA tissue concentrations and incidence of
      pansteatitis or fish health status. Results revealed that healthy tilapia
      exhibited an overall higher (p-value<0.05) PFAA burden than pansteatitis-affected
      tilapia across all tissues. Further analysis showed that organs previously noted
      in the literature to contain the highest PFAA concentrations, such as kidney,
      liver, and plasma, were the organs driving the difference in PFAA burden between
      the two tilapia groups. Care must be taken in the interpretations we draw from
      not only the results of our study, but also other PFAA measurements made on
      populations (human and wildlife alike) under differing health status.

PMID- 29191317
TI  - SeaNine 211 as antifouling biocide: A coastal pollutant of emerging concern.
AB  - SeaNine 211, with 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) being the
      biocidal ingredient, is a widely-used antifouling agent to deter the undesirable
      biofouling phenomenon. It is commercially promoted as an environmentally
      acceptable antifoulant mainly due to its claimed rapid degradation in marine
      environment. However, increasing researches document varying degradative kinetics
      in different environments, proving that SeaNine 211 is actually not degraded
      equally fast around the world (half-life between <1day and 13.1days). Large-scale
      application of SeaNine 211 in antifouling coatings has also caused global
      contamination of marine environment in various compartments. For example,
      accumulation of SeaNine 211 is detected as high as 3700ng/L in Spanish seawater
      and 281ng/g dry weight in Korean sediment. Considering that SeaNine 211 is highly
      toxic against non-target marine organisms, environmental risk assessment finds
      that most marine organisms are endangered by SeaNine 211 in worst-case scenario.
      Its endocrine disrupting and reproductive impairing effects at environmentally
      worst-case concentrations further constitute a long-term threat to the
      maintenance of population stability. Therefore, in the light of the varying
      degradability, environmental pollution and high toxicity, especially the
      endocrine disruption, SeaNine 211 as an antifouling agent is likely to cause non
      negligible damages to the marine ecosystem. There is an urgency to perform a
      systematic ecological risk assessment of SeaNine 211 to prevent the potential
      impacts on the health of marine environment. A regular monitoring also becomes
      necessary to place the usage of antifouling biocides under control.

PMID- 29191318
TI  - Contribution of precursor compounds to the release of per- and polyfluoroalkyl
      substances (PFASs) from waste water treatment plants (WWTPs).
AB  - Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in sludge and water
      from waste water treatment plants, as a result of their incorporation in everyday
      products and industrial processes. In this study, we measured several classes of
      persistent PFASs, precursors, transformation intermediates, and newly identified
      PFASs in influent and effluent sewage water and sludge from three municipal waste
      water treatment plants in Sweden, sampled in 2015. For sludge, samples from 2012
      and 2014 were analyzed as well. Levels of precursors in sludge exceeded those of
      perfluoroalkyl acids and sulfonic acids (PFCAs and PFSAs), in 2015 the sum of
      polyfluoroalkyl phosphoric acid esters (PAPs) were 15-20ng/g dry weight, the sum
      of fluorotelomer sulfonic acids (FTSAs) was 0.8-1.3ng/g, and the sum of
      perfluorooctane sulfonamides and ethanols ranged from non-detected to 3.2ng/g.
      Persistent PFSAs and PFCAs were detected at 1.9-3.9ng/g and 2.4-7.3ng/g dry
      weight, respectively. The influence of precursor compounds was further
      demonstrated by an observed substantial increase for a majority of the persistent
      PFCAs and PFSAs in water after waste water treatment. Perfluorohexanoic acid
      (PFHxA), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS),
      and perfluorooctane sulfonic acid (PFOS) had a net mass increase in all WWTPs,
      with mean values of 83%, 28%, 37% and 58%, respectively. The load of precursors
      and intermediates in influent water and sludge combined with net mass increase
      support the hypothesis that degradation of precursor compounds is a significant
      contributor to PFAS contamination in the environment.

PMID- 29191319
TI  - Rate of hexabromocyclododecane decomposition and production of brominated
      polycyclic aromatic hydrocarbons during combustion in a pilot-scale incinerator.
AB  - Here, we examined the incineration of extruded polystyrene containing
      hexabromocyclododecane (HBCD) in a pilot-scale incinerator under various
      combustion temperatures (800-950 degrees C) and flue gas residence times (2
      8sec). Rates of HBCD decomposition ranged from 99.996% (800 degrees C, 2sec) to
      99.9999% (950 degrees C, 8sec); the decomposition of HBCD, except during the
      initial stage of combustion (flue gas residence time<2sec), followed a pseudo
      first-order kinetics model. An Arrhenius plot revealed that the activation energy
      and frequency factor of the decomposition of HBCD by combustion were 14.2kJ/mol
      and 1.69sec-1, respectively. During combustion, 11 brominated polycyclic aromatic
      hydrocarbons (BrPAHs) were detected as unintentional by-products. Of the 11
      BrPAHs detected, 2-bromoanthracene and 1-bromopyrene were detected at the highest
      concentrations. The mutagenic and carcinogenic BrPAHs 1,5-dibromoanthracene and 1
      bromopyrene were most frequently detected in the flue gases analyzed. The total
      concentration of BrPAHs exponentially increased (range, 87.8-2,040,000ng/m3) with
      increasing flue gas residence time. Results from a qualitative analysis using gas
      chromatography/high-resolution mass spectrometry suggest that bromofluorene and
      bromopyrene (or fluoranthene) congeners were also produced during the combustion.

PMID- 29191320
TI  - Distribution characteristics of poly- and perfluoroalkyl substances in the
      Yangtze River Delta.
AB  - In this work, a method was developed and optimized for the analysis of
      polyfluoroalkyl and/or perfluoroalkyl substances (PFASs) content in surface water
      and sediment samples with high instrumental response and good separation. Surface
      water and sediment samples were collected from the Yangtze River Delta (YRD) to
      analyze the distribution characteristics of perfluoroalkyl carboxylic acids
      (PFCAs), perfluoroalkane sulfonic acids (PFSAs), perfluoroalkyl phosphonic acids
      (PFPAs), perfluoroalkyl phosphinic acids (PFPiAs), and polyfluoroalkyl phosphoric
      acid diesters (diPAPs). The results showed that the total concentrations of PFCAs
      and PFSAs in YRD varied from 31 to 902ng/L. PFCAs (>=11 carbons) and PFSAs (>=10
      carbons atoms) were not detected in any surface water samples. The mean
      concentrations of all PFCAs and PFSAs in surface water from the sampling areas
      decreased in the following order: Yangtze river (191ng/L)~Taihu lake
      (189ng/L)>Huangpu river (122ng/L)~Qiantang river (120ng/L)>Jiaxing urban river
      (100ng/L). Strong significant (p<0.05) correlations between the concentrations of
      many of the compounds were found in the sampling areas, suggesting a common
      source for these compounds. Only perfluorooctanoic acid (PFOA) was observed in
      all sediment samples, at concentrations varying from 0.02 to 1.35ng/g. Finally,
      detection rates of two diPAPs were only 8% and 10%, respectively and the
      concentration of diPAPs was two to three times lower compared to PFCAs and PFSAs.

PMID- 29191321
TI  - Abdominal Obesity Is Associated With an Increased Risk of All-Cause Mortality in
      Patients With HFpEF.
AB  - BACKGROUND: There is a lack of studies that evaluate the association between
      abdominal obesity and subsequent outcomes in patients with heart failure with
      preserved ejection fraction (HFpEF). OBJECTIVES: The present study aimed to
      assess the association between abdominal obesity and risk of all-cause mortality
      in patients with HFpEF. METHODS: The present study used data from the TOPCAT
      (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone
      Antagonist) trial. The primary outcome was all-cause mortality. We analyzed and
      compared the hazard ratios (HRs) in patients with abdominal obesity and those
      without abdominal obesity using multivariable Cox proportional hazard models.
      Abdominal obesity was defined as a waist circumference of >=102 cm in men and
      >=88 cm in women. RESULTS: The present study included 3,310 patients with HFpEF:
      2,413 patients with abdominal obesity and 897 without abdominal obesity. The mean
      follow-up was 3.4 +/- 1.7 years. During follow-up, 500 patients died. All-cause
      mortality rates in patients with and without abdominal obesity were 46.1 and 40.7
      events per 1,000 person-years, respectively. After multivariable adjustment, the
      risk of all-cause mortality was significantly higher in patients with abdominal
      obesity than in those without abdominal obesity (adjusted HR: 1.52; 95%
      confidence interval [CI]: 1.16 to 1.99; p = 0.002). The risk of cardiovascular
      and noncardiovascular mortality was also significantly higher in patients with
      abdominal obesity than in those without abdominal obesity (adjusted HR: 1.50; 95%
      CI: 1.08 to 2.08; p = 0.01 and adjusted HR: 1.58; 95% CI: 1.00 to 2.51; p = 0.04,
      respectively). CONCLUSIONS: The risk of all-cause mortality was significantly
      higher in patients with HFpEF with abdominal obesity than in those without
      abdominal obesity.

PMID- 29191322
TI  - Adipose Composition and Heart Failure Prognosis: Paradox or Not?

PMID- 29191324
TI  - TAVR for Severe Aortic Regurgitation: Advancing the Frontier.

PMID- 29191326
TI  - PFO and Migraine: The Blind Leading the Blinded.

PMID- 29191325
TI  - Percutaneous Closure of Patent Foramen Ovale in Patients With Migraine: The
      PREMIUM Trial.
AB  - BACKGROUND: Migraine is a prevalent and disabling disorder. Patent foramen ovale
      (PFO) has been associated with migraine, but its role in the disorder remains
      poorly understood. OBJECTIVES: This study examined the efficacy of percutaneous
      PFO closure as a therapy for migraine with or without aura. METHODS: The PREMIUM
      (Prospective, Randomized Investigation to Evaluate Incidence of Headache
      Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to
      Medical Management) was a double-blind study investigating migraine
      characteristics over 1 year in subjects randomized to medical therapy with a sham
      procedure (right heart catheterization) versus medical therapy and PFO closure
      with the Amplatzer PFO Occluder device (St. Jude Medical, St. Paul, Minnesota).
      Subjects had 6 to 14 days of migraine per month, had failed at least 3 migraine
      preventive medications, and had significant right-to-left shunt defined by
      transcranial Doppler. Primary endpoints were responder rate defined as 50%
      reduction in migraine attacks and adverse events. Secondary endpoints included
      reduction in migraine days and efficacy in patients with versus without aura.
      RESULTS: Of 1,653 subjects consented, 230 were enrolled. There was no difference
      in responder rate in the PFO closure (45 of 117) versus control (33 of 103)
      groups. One serious adverse event (transient atrial fibrillation) occurred in 205
      subjects who underwent PFO closure. Subjects in the PFO closure group had a
      significantly greater reduction in headache days (-3.4 vs. -2.0 days/month, p =
      0.025). Complete migraine remission for 1 year occurred in 10 patients (8.5%) in
      the treatment group versus 1 (1%) in the control group (p = 0.01). CONCLUSIONS:
      PFO closure did not meet the primary endpoint of reduction in responder rate in
      patients with frequent migraine. (Prospective, Randomized Investigation to
      Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using
      the AMPLATZER PFO Occluder to Medical Management [PREMIUM]; NCT00355056).

PMID- 29191323
TI  - Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation.
AB  - BACKGROUND: Limited data exist about safety and efficacy of transcatheter aortic
      valve replacement (TAVR) in patients with pure native aortic regurgitation (AR).
      OBJECTIVES: This study sought to compare the outcomes of TAVR with early- and new
      generation devices in symptomatic patients with pure native AR. METHODS: From the
      pure native AR TAVR multicenter registry, procedural and clinical outcomes were
      assessed according to VARC-2 criteria and compared between early- and new
      generation devices. RESULTS: A total of 331 patients with a mean STS score of 6.7
      +/- 6.7 underwent TAVR. The early- and new-generation devices were used in 119
      patients (36.0%) and 212 patients (64.0%), respectively. STS score tended to be
      lower in the new-generation device group (6.2 +/- 6.7 vs. 7.6 +/- 6.7; p = 0.08),
      but transfemoral access was more frequently used in the early-generation device
      group (87.4% vs. 60.8%; p < 0.001). Compared with the early-generation devices,
      the new-generation devices were associated with a significantly higher device
      success rate (81.1% vs. 61.3%; p < 0.001) due to lower rates of second valve
      implantation (12.7% vs. 24.4%; p = 0.007) and post-procedural AR >= moderate
      (4.2% vs. 18.8%; p < 0.001). There were no significant differences in major 30
      day endpoints between the 2 groups. The cumulative rates of all-cause and
      cardiovascular death at 1-year follow-up were 24.1% and 15.6%, respectively. The
      1-year all-cause mortality rate was significantly higher in the patients with
      post-procedural AR >= moderate compared with those with post-procedural AR <=
      mild (46.1% vs. 21.8%; log-rank p = 0.001). On multivariable analysis, post
      procedural AR >= moderate was independently associated with 1-year all-cause
      mortality (hazard ratio: 2.85; 95% confidence interval: 1.52 to 5.35; p = 0.001).
      CONCLUSIONS: Compared with the early-generation devices, TAVR using the new
      generation devices was associated with improved procedural outcomes in treating
      patients with pure native AR. In patients with pure native AR, significant post
      procedural AR was independently associated with increased mortality.

PMID- 29191327
TI  - Optogenetic Modulation of Cardiac Sympathetic Nerve Activity to Prevent
      Ventricular Arrhythmias.
AB  - BACKGROUND: Studies have shown that left stellate ganglion (LSG) suppression
      protects against ventricular arrhythmias (VAs). Optogenetics is a novel technique
      to reversibly regulate the activity of the targeted neurons. OBJECTIVES: This
      study aimed to investigate whether an optogenetically silenced LSG could protect
      against VAs induced by myocardial ischemia. METHODS: Adeno-associated virus (AAV)
      was used as the vector to deliver ArchT, an inhibitory light-sensitive opsin, to
      the LSG neurons. Twenty male beagles were randomized into the optogenetics group
      (n = 10, AAV2/9-CAG-ArchT-GFP microinjected into LSG) and control group (n = 10,
      AAV2/9-CAG-GFP microinjected into LSG). After 4 weeks, the LSG function and
      neural activity, heart rate variability, ventricular action potential duration,
      and effective refractory period were measured in the absence or presence of a
      light-emitting diode illumination (565 nm). Myocardial ischemia was induced by
      left anterior coronary artery ligation and 1 h of electrocardiography was
      recorded for VAs analysis. RESULTS: ArchT was successfully expressed in all dogs.
      Transient light-emitting diode illumination significantly suppressed the LSG
      function, LSG neural activity, and sympathetic nerve indices of heart rate
      variability as well as prolonged left ventricular effective refractory period and
      APD90 only in the optogenetics group. Thirty-minute illumination further enhanced
      these changes in the optogenetics group. Importantly, all of these changes
      returned to baseline within 2 h after illumination was turned off. Moreover, the
      ischemia-induced VAs were significantly suppressed by illumination only in the
      optogenetics group. CONCLUSIONS: Optogenetic modulation could reversibly inhibit
      the neural activity of LSG, thereby increasing electrophysiological stability and
      protecting against myocardial ischemia-induced VAs.

PMID- 29191328
TI  - Optogenetic Neuromodulation of the Heart.

PMID- 29191329
TI  - The Evolving Nature of Infective Endocarditis in Spain: A Population-Based Study
      (2003 to 2014).
AB  - BACKGROUND: Little information exists regarding population-based epidemiological
      changes in infective endocarditis (IE) in Europe. OBJECTIVES: This study sought
      to analyze temporal trends in IE in Spain from 2003 to 2014. METHODS: This
      retrospective, population-based, temporal trend study analyzed the incidence,
      epidemiological and clinical characteristics, and outcome of all patients
      discharged from hospitals included in the Spanish National Health System with a
      diagnosis of IE, from January 2003 to December 2014. RESULTS: Overall, 16,867
      episodes of IE were identified during the study period, 66.3% in men. The rate of
      IE significantly increased, from 2.72 in 2003 to 3.49 per 100,000 person-years in
      2014, and this rise was higher among older adults. The most frequent
      microorganisms were staphylococci (28.7%), followed by streptococci (20.4%) and
      enterococci (13.1%). Twenty-three percent of patients underwent cardiac surgery.
      The in-hospital mortality rate was 20.4%. Throughout the study period, the
      proportion of patients with previously known heart valve disease and diabetes
      mellitus significantly increased, whereas the prevalence of intravenous drug use
      decreased. Regarding microorganisms, Staphylococcus aureus and streptococci
      slightly declined, whereas coagulase-negative staphylococci and enterococci
      consistently increased over the years. In-hospital complications and cardiac
      surgery rates significantly increased across the years. The risk-adjusted in
      hospital mortality rate diminished (0.2% per year) during the study period.
      CONCLUSIONS: The incidence of IE episodes significantly increased over the decade
      of the study period, particularly among older adults. Relevant changes in
      clinical and microbiological profile included older patients with more
      comorbidity and a rise in enterococci and coagulase-negative staphylococcal
      infections. Adjusted mortality rates slightly declined over the study period.

PMID- 29191330
TI  - Is Infective Endocarditis Changing Over Time?

PMID- 29191333
TI  - Current State of Public Reporting.

PMID- 29191332
TI  - Role of Payers in the Development of Cardiovascular Therapeutics: Misalignment
      Between Approval and Reimbursement.
AB  - Regulators and payers have contrasting priorities that can lead to divergent
      decisions and delays in patient access to new treatments. Those involved in
      coverage decisions have not routinely been integrated in the drug development
      process. Theoretically, inclusion of payer representatives early in development
      could help discern discordance among stakeholder priorities; facilitate
      cooperation to align objectives; foster agreement on the evidence required for
      approval and reimbursement; improve transparency, accountability, and consistency
      of payer decision making; and ideally, minimize delays in patient access to new
      therapies. However, early participation by payers may not provide these expected
      benefits if payers' decision-making processes are not evidence based or cannot be
      reliably predicted. This paper describes current interactions among regulatory
      agencies, payers, sponsors, and investigators and proposes collaboration among
      all stakeholders earlier in the development process. The premise that a priori
      discussions might facilitate the delivery of advances in cardiovascular care is a
      hypothesis worth testing.

PMID- 29191331
TI  - Genome Editing: The Recent History and Perspective in Cardiovascular Diseases.
AB  - The genome-editing field has advanced to a remarkable degree in the last 5 years,
      culminating in the successful correction of a cardiomyopathy gene mutation in
      viable human embryos. In this review, the author discusses the basic principles
      of genome editing, recent advances in clustered regularly interspaced short
      palindromic repeats and clustered regularly interspaced short palindromic repeats
      associated 9 technology, the impact on cardiovascular basic science research,
      possible therapeutic applications in patients with cardiovascular diseases, and
      finally the implications of potential clinical uses of human germline genome
      editing.

PMID- 29191334
TI  - Treatment of Secondary Mitral Regurgitation in Chronic Heart Failure.

PMID- 29191335
TI  - Coronary Microvascular Dysfunction Identifies Patients at High Risk of Adverse
      Events Across Cardiometabolic Diseases.

PMID- 29191336
TI  - Could the Interplay Between Macrophages and Fibroblasts Drive Extracellular
      Matrix Dynamics in End-Stage Heart Failure?

PMID- 29191337
TI  - Reply: Could the Interplay Between Macrophages and Fibroblasts Drive
      Extracellular Matrix Dynamics in End-Stage Heart Failure?

PMID- 29191338
TI  - Reply: Importance of Resting Coronary Blood Flow as the Main Determinant of
      Coronary Flow Reserve.

PMID- 29191339
TI  - Importance of Resting Coronary Blood Flow as the Main Determinant of Coronary
      Flow Reserve.

PMID- 29191341
TI  - Approach to the total body skin examination in adults and children: Kids are not
      just little people.
AB  - The indications, evidence for, and approach to performing a total body skin
      examination differs for adult versus pediatric patients. To provide optimal care
      to all of our patients, dermatologists should recognize these differences and
      feel comfortable and competent in performing a total body skin examination in
      patients of all ages.

PMID- 29191340
TI  - Kids are not just little people: Part III.

PMID- 29191342
TI  - Cutaneous sign of abuse: Kids are not just little people.
AB  - Skin injury is the most common form of child physical abuse. Although the pattern
      and visual appearance of skin injury and the treatment needed for the injury is
      similar in children and adults, characteristics of infant and childhood skin may
      complicate the diagnosis of injury. A good understanding of normal developmental
      presentation of accidental injury from infancy to adulthood, locations for injury
      that should trigger consideration of abuse, and cutaneous mimics of abuse across
      the lifespan are critical to the identification of suspected abuse. Adults and
      older children can provide a history directly to providers, though it should be
      noted that abused adults and children may not always disclose the true cause of
      their injuries. In infants and very young children, a history from the patient is
      lacking due to the verbal abilities of the child, and a parent or other caregiver
      may provide a false or misleading history that can complicate the diagnosis and
      treatment. The approach to taking the history, when abuse is suspected, is a
      critical part of the evaluation, and best practice will vary depending on whether
      your patient is a child or an adult.

PMID- 29191343
TI  - An age-based approach to dermatologic surgery: Kids are not just little people.
AB  - Surgical dermatologic procedures in children pose unique challenges that differ
      from those in adults. Child and parental anxiety, along with procedural anxiety
      in adults, necessitate different approaches. Special considerations are reviewed
      in the application of topical anesthesia and administration of local anesthesia
      in children as opposed to adults, and the use and safety of general anesthesia in
      children is highlighted. In addition, management of postprocedural analgesia
      differs in children, largely due to concern for safety of opioids in children.

PMID- 29191344
TI  - Malignant skin tumors: Kids are not just little people.
AB  - Skin tumors are a clinically heterogeneous group of dermatologic conditions that
      affect both children and adults. Although similar types of skin tumors can affect
      both children and adults, the epidemiology, pathogenesis, and treatment of these
      skin neoplasms can vary drastically in children compared with adults. Despite the
      clear need for literature elucidating the differences of skin tumors in children
      compared with adults, there is a serious dearth of scientific contributions
      addressing this area. This contribution highlights the types of differences that
      can occur between adults and children with skin neoplasms, as well as the special
      considerations that need to be recognized when managing skin tumors in children
      by providing a comparative analysis of basal cell carcinoma, squamous cell
      carcinoma, and Kaposi sarcoma occurring in adults with these same tumors
      occurring in children. Specifically, we examine the aforementioned tumors with a
      focus on (1) epidemiology, (2) etiology, (3) clinical presentation, (4) workup,
      and (5) treatment.

PMID- 29191345
TI  - Vasculitis: Kids are not just little people.
AB  - Cutaneous vasculitis, inflammatory destruction of blood vessels, can present with
      a wide range of clinical and pathologic findings across a number of heterogeneous
      conditions. Although some vasculitides are present in both children and adults,
      some important differences exist in clinical presentation, etiology, management,
      and prognosis in childhood vasculitis versus adult vasculitis. Cutaneous
      vasculitis is rare in children, and most childhood vasculitides, of which Henoch
      Schonlein purpura is the most common, histologically are small vessel
      leukocytoclastic vasculitis. In children, infectious etiologies are more common
      than in adults. Childhood cutaneous vasculitis is most often self-limited with a
      good prognosis, and treatment is mainly supportive. (c) 2017 Elsevier Inc. All
      rights reserved.

PMID- 29191346
TI  - Neutrophilic dermatoses: Kids are not just little people.
AB  - Neutrophilic dermatoses are a group of inflammatory skin disorders characterized
      by an overactive innate immune system with dysregulation of neutrophils without
      underlying infectious etiology. The major representative conditions discussed are
      Sweet syndrome; pyoderma gangrenosum; neutrophilic eccrine hidradenitis;
      palmoplantar eccrine hidradenitis; subcorneal pustular dermatoses; bowel
      associated dermatosis arthritis syndrome; and synovitis, acne, pustulosis,
      hyperostosis, and osteitis. We will also discuss other neutrophilic conditions
      present almost exclusively in the pediatric population, including congenital
      erosive and vesicular dermatosis with reticulated supple scarring and the
      recently described group of autoinflammatory diseases. The clinical
      characteristics, diagnostic approach, and treatment management in the pediatric
      and adult population are discussed.

PMID- 29191347
TI  - Granulomatous diseases: Kids are not just little people.
AB  - Granulomatous diseases represent a heterogeneous group of conditions
      characterized by histiocytic inflammation that affect patients of any age. These
      diseases differ widely in their pathogenesis and include infectious and
      noninfectious conditions. This review focuses on noninfectious granulomatous
      conditions, with particular emphasis on age-related differences in the onset,
      epidemiology, clinical manifestations, prognosis, and age-specific management of
      specific granulomatous disorders. Knowledge of age-specific aspects of
      granulomatous conditions in adults and children improves both the extent of the
      diagnostic workup and the management of these patients.

PMID- 29191348
TI  - Cutaneous adverse drug reactions: Kids are not just little people.
AB  - Cutaneous adverse drug reactions are a common complication of drug therapy and
      affect patients of all ages. Despite the daunting frequency at which these
      reactions occur, there are no scientific contributions comparing cutaneous
      adverse drug reactions in adults to those occurring in children. Literature
      delineating such differences is important given that there are significant age
      related differences in the pharmacokinetics of many drugs and that most of the
      package-insert data on adverse drug reactions are based on preclinical trials
      that do not include children as participants. This contribution attempts to
      bridge the literature gap by examining five cutaneous adverse drug reactions that
      occur in both adults and children, highlighting the many types of age-related
      differences, with a special emphasis on comparisons of (1) epidemiology, (2)
      etiology, (3) clinical presentation, (4) workup, and (5) treatment.

PMID- 29191349
TI  - Clinical trials: Kids are not just little people.
AB  - Clinical trials are the backbone of modern evidence-based medicine. They are the
      vital bridge between research-based discovery and cutting edge patient care.
      Randomized, controlled clinical trials are the gold standard of medical research,
      providing a method for evaluation and discovery of novel therapies that improve
      and even save lives. Despite an increase in the number of pediatric and adult
      clinical trials over recent decades, this growth has not been equal among these
      populations. The volume of clinical trials involving children lags substantially
      behind their adult counterparts. Children are not simply little adults. As a
      result, extrapolating results from adult clinical trials to the treatment of
      children may be inappropriate and, possibly, harmful. In this review, we discuss
      the intricacies of performing clinical trials in all patients and stress the
      unique distinguishing characteristics of pediatric clinical trials.

PMID- 29191350
TI  - Teledermatology: Kids are not just little people.
AB  - Teledermatology has emerged as a promising solution for pediatric and adult
      patients accessing dermatologic care in a health care environment fraught with
      barriers to access. Teledermatology has been extensively evaluated in terms of
      diagnostic accuracy, clinical outcomes, patient and provider satisfaction, and
      costs, relative to traditional health care delivery models. Current research
      indicates that teledermatology is effective and efficient in diagnosis and
      management of skin diseases. The majority of studies on the subject, however,
      rely on adult patient data. Pediatric patients, with their unique clinical
      features and challenges, may interact with telemedicine differently than their
      adult counterparts. Maximizing the benefits of teledermatology in pediatric
      dermatologic care is dependent on future research. We review and analyze the
      commonalities and differences between pediatric and adult patient care using
      teledermatology.

PMID- 29191351
TI  - How issues of autonomy and consent differ between children and adults: Kids are
      not just little people.
AB  - Decision making in dermatology practice with adult patients is in most cases a
      relatively straightforward process, involving a back-and-forth exchange of
      information, ideas and opinions between the physician and patient. This process
      is more complex in the field of pediatric dermatology. It involves the triad of
      the patient, parent or guardian, and physician. It utilizes a model, common to
      many fields in pediatrics, whereby the physician seeks to obtain informed
      permission from the parent with the assent of the child, all the while
      endeavoring to act in the best interests of the child. This model can be
      challenged in many ways; from parents seeking interventions, which are not in the
      best interests of the child, to a child refusing to assent to a procedure that is
      deemed necessary by the parent and physician. We review the theory, terminology,
      and guidelines relevant to the ethics of decision making when working with
      children compared with adults. We explore approaches to a variety of ethically
      challenging situations that may be encountered by the dermatologist, through
      their work with pediatric patients.

PMID- 29191353
TI  - Editorial Comment.

PMID- 29191352
TI  - Predatory journals and dishonesty in science.
AB  - Predatory magazines are created by unreliable publishers who, after collecting a
      fee, publish the submitted paper in the Open Access (OA) formula without
      providing substantive control. For the purpose of "encouraging" authors to submit
      their work, they often impersonate existing periodicals by using a similar
      sounding title, a similar webpage, and copied names of editors of the editorial
      board. They also offer credits close in name to the Impact Factor. The purpose of
      such activity is to deceive authors and to earn money in an unfair manner. This
      contribution presents mechanisms used by such journals and includes suggestions
      for protection from the duplicity and the subsequent disappointment of
      publishing, often for an exorbitant fee.

PMID- 29191354
TI  - Alliances: fair or lethal.
AB  - Alliances are necessary for the development of individuals, institutions, and
      civilizations. Optimally, alliances provide benefits to their components;
      nevertheless, gains are not always symmetrical. Some alliances may prove
      detrimental or even lethal to some or all of the allies. I analyze some types of
      covenants using examples of history to provide a framework for drawing salient
      features of the alliance between the legal and the medical professions. This
      joint effort should be inherently beneficial to both; yet, particularly in the
      United States, the equilibrium is skewed against the medical profession. If it is
      not redressed, medicine and its specialties-in particular, dermatology-will go
      into a decline and wilt.

PMID- 29191355
TI  - Clinical and prognostic factors in the development of basal cell carcinoma.
AB  - We investigated the environmental and personal risk factors associated with the
      development of basal cell carcinoma (BCC). This retrospective cohort study
      included a total of 997 patients whose diagnosis was confirmed by histopathologic
      examination between 2007 and 2014. A control examination was performed in 363 of
      these patients, who were accessed via telephone. A total of 1151 tumors were
      detected in 997 patients. During their follow-up, 13% of them developed
      subsequent tumors. The risk of developing subsequent tumor was 2.7-fold higher in
      patients with multiple BCCs at the time of diagnosis than those with single BCC.
      Multiple BCCs tended to develop in older patients and men. The risk of developing
      multiple BCCs was increased in patients with a history of BCC, skin type 1 or 2,
      and chronic sun exposure (sun exposure of >500 weeks, a high photoaging score
      [>=30], and the presence of actinic keratosis). We concluded that chronic sun
      exposure may increase the risk of developing multiple BCCs. These data also
      indicate that cumulative sun exposure is as important for developing BCC as for
      squamous cell carcinoma.

PMID- 29191356
TI  - A novel modality for intraoperative margin assessment and its impact on re
      excision rates in breast conserving surgery.
AB  - BACKGROUND: A single center retrospective chart review was performed examining
      the ability of a novel radiofrequency probe (Margin Probe; Dune Medical Devices,
      Caesarea, Israel) for intraoperative margin assessment to reduce the number of
      reexcisions in breast-conserving surgery. METHODS: Reexcision rates were
      evaluated in one-hundred and twenty consecutive patients before and after the
      institution of the device. Utility of the device was evaluated by comparing
      intraoperative feedback with postoperative pathology reports. RESULTS: Two
      hundred and forty patient subjects were reviewed in total. There was a
      significant decrease in the re-lumpectomy rate (50%, p = 0.039) in the device
      group without increasing the total volume of tissue resected. CONCLUSIONS: The
      use of the MarginProbe device as an adjunct to the standard of care resulted in
      reduction of positive margins after lumpectomy and the number of re-excisions,
      significantly improving outcomes in breast-conserving surgery at our institution.

PMID- 29191357
TI  - Patient-specific evolution of renal function in chronic heart failure patients
      dynamically predicts clinical outcome in the Bio-SHiFT study.
AB  - Renal dysfunction is an important component of chronic heart failure (CHF), but
      its single assessment does not sufficiently reflect clinically silent progression
      of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate
      temporal evolutions of glomerular and tubular markers in 263 stable patients with
      CHF, and to determine if their patient-specific evolutions during this clinically
      silent period can dynamically predict clinical outcome. We determined the risk of
      clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac
      death, Left Ventricular Assist Device placement, and heart transplantation) in
      relation to marker levels, slopes and areas under their trajectories. In each
      patient, the trajectories were estimated using repeatedly measured glomerular
      markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C
      (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and
      kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase
      associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on
      average 8 urine and 9 plasma samples per patient. All glomerular markers
      predicted the endpoint (univariable hazard ratio [95% confidence interval] per
      20% increase: creatinine: 1.18[1.07-1.31], CysC: 2.41[1.81-3.41], and per 20%
      eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted
      the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes
      were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76[1.52
      2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]).
      Associations persisted after multivariable adjustment for clinical
      characteristics. Thus, during clinically silent progression of CHF, glomerular
      and tubular functions deteriorate, but not simultaneously. Hence, patient
      specific evolutions of these renal markers dynamically predict clinical outcome
      in patients with CHF.

PMID- 29191358
TI  - [Stereotactic body radiation therapy for oligometastatic prostate cancer].
AB  - INTRODUCTION: The first line treatment of metastatic prostate cancer is medical
      or surgical androgen-deprivation. This treatment however has significant side
      effects that can affect the patients' quality of life. For oligometastatic
      patients, a new therapeutic approach, focusing on local treatment of metastases,
      is emerging. METHODS: A systematic review of studies published on Stereotactic
      Body Radiation Therapy (SBRT) for oligometastatic prostate cancer was performed
      using results from search request on MEDLINE. RESULTS: Treatment regimens vary
      from a single fraction of 20Gy (bone lesions) to ten fractions for a total dose
      of 64Gy (visceral metastases). Local control is 95.5 to 100% at 2 years with
      grade 1 and 2 toxicities around 10%, without any grade 3 side effects. These
      retrospective studies show the feasibility and very low toxicity of SBRT for this
      population of patients. The effect of SBRT on disease-free or global survival and
      quality of life has not been assessed. Several prospective trials (STOMP &
      ORIOLE) are underway. CONCLUSION: Treating patients with up to five prostate
      cancer metastases is efficient and has a low toxicity. Prospective trials should
      identify which patients, if any, really benefit from this approach.

PMID- 29191359
TI  - Evaluation of Esophageal Anastomotic Integrity With Serial Pleural Amylase
      Levels.
AB  - BACKGROUND: An anastomotic leak is the most devastating and potentially fatal
      complication after esophagectomy. Current detection methods can be inaccurate and
      place patients at risk of other complications. Analysis of pleural fluid for
      amylase may be more accurate and place patients at less of a risk for evaluating
      the integrity of an esophageal anastomosis. METHODS: We retrospectively reviewed
      prospective data of 45 consecutive patients who underwent an Ivor Lewis
      esophagectomy over an 18-month period and evaluated their anastomotic integrity
      with serial pleural amylase levels (PAL). RESULTS: There were 40 men (89%), and
      median age was 63 years (range, 35 to 79). Indication for esophagectomy was
      cancer in 38 patients (84%); 27 (71%) underwent neoadjuvant chemoradiation. A
      barium swallow was performed in the first 25 patients at median postoperative day
      (POD) 5 (range, 5 to 10); the swallow was negative in 23 patients (93%). Serial
      PALs were obtained starting on POD 3 and stopped 1 day after toleration of clear
      liquids. The PALs in the no-leak patients were highest on POD 3 (median 42 IU/L;
      range, 20 to 102 IU/L) and decreased (median 15 IU/L; range, 8 to 34 IU/L) to the
      lowest levels 1 day after clear liquid toleration (p = 0.04). Two patients had a
      leak and had peak PALs of 227 IU/L and 630 IU/L, respectively; both leaks
      occurred on POD 4, 1 day before their scheduled swallow test. The last 20
      patients underwent serial PALs only, without a planned swallow test or computed
      tomography scan for anastomotic integrity evaluation. One of these patients had a
      leak on POD 5 with a low PAL of 55 IU/L the day before the spike of more than
      4,000 IU/L. Two of the leaks were treated with esophageal stent placement and
      intravenous antibiotics, and the remaining patient's leak resolved with
      intravenous antibiotics, no oral intake, and observation only. None of the leak
      patients required transthoracic esophageal repair or drainage of an empyema.
      There was 1 postoperative death (2%) secondary to aspiration pneumonia on POD 10;
      no leak was ever identified, and the patient had been eating for 3 days before
      death. Complications occurred in 15 patients (33%), most commonly respiratory; no
      respiratory issues occurred in PAL-only evaluated patients. No late anastomotic
      leaks occurred in any patient while in the hospital or after discharge.
      CONCLUSIONS: Serial PALs for the detection of esophageal anastomotic leaks proved
      to be accurate, safe, and inexpensive. Elimination of barium swallows and
      computed tomography scans for evaluation of anastomotic integrity may decrease
      aspiration risks as well as associated pulmonary failure during the postoperative
      period. Serial PALs may be the preferred method of detecting an anastomotic leak
      after esophagectomy. A prospective randomized study is warranted.

PMID- 29191360
TI  - Early Mentoring of Medical Students and Junior Doctors on a Path to Academic
      Cardiothoracic Surgery.
AB  - BACKGROUND: In 2005 the Department of Cardiothoracic Surgery at The Royal
      Children's Hospital started an early academic mentoring program for medical
      students and junior doctors with the aim of fostering an interest in academic
      surgery. METHODS: Between 2005 and 2015, 37 medical students and junior doctors
      participated in research in the Department of Cardiothoracic Surgery at The Royal
      Children's Hospital. Each was given an initial project on which to obtain ethics
      approval, perform a literature review, data collection, statistical analysis, and
      prepare a manuscript for publication. A search of the names of these former
      students and doctors was conducted on PubMed to identify publications. RESULTS: A
      total of 113 journal articles were published in peer-reviewed journals with an
      average impact factor of 4.1 (range, 1.1 to 19.9). Thirty (30 of 37, 81%)
      published at least one article. A mean of 4.3 journal articles was published per
      student or junior doctor (range, 0 to 29). Eleven (11 of 37, 30%) received
      scholarships for their research. Nine (9 of 37, 24%) have completed or are
      enrolled in higher research degrees with a cardiothoracic surgery focus. Of these
      9, 2 have completed doctoral degrees while in cardiothoracic surgery training.
      Five will complete their cardiothoracic surgery training with a doctoral degree
      and the other 2 are pursuing training in cardiology. CONCLUSIONS: A successful
      early academic mentoring program in a busy cardiothoracic surgery unit is
      feasible. Mentoring of motivated individuals in academic surgery benefits not
      only their medical career, but also helps maintain high academic output of the
      unit.

PMID- 29191362
TI  - Current conditions and colonization history asymmetrically shape the organization
      of shallow sessile communities after simulated state shifts.
AB  - Historical processes affecting biological organization are rarely considered when
      predicting the effects of disturbance on community structure. In order to assess
      the relative importance of historical and post-disturbance conditions as
      determinants of community structure, we undertook reciprocal transplants, at
      different successional stages, of sessile communities developing at recreational
      piers that were previously observed to show contrasting fish predation pressure
      and settlement rate in the Sao Sebastiao Channel, Brazil. Regardless the
      direction of state shift, after 15 weeks communities converged to the destination
      site structure, substantially drifting away from the path observed at origin,
      therefore revealing high susceptibility to environmental change. Although
      converging, transplanted communities never matched the destination standard in
      both transplant directions, suggesting that history still mattered, as providing
      some legacy that lasted, at least, for 15 weeks. The taxonomic groups resisting
      community drift were hard-bodied invertebrates, which could eventually provide
      some resilience to these communities through ecosystem engineering.

PMID- 29191361
TI  - Comparing the effects of fluticasone, anti-IgE and anti-TNF treatments in a
      chronic asthma model.
AB  - BACKGROUND: Corticosteroids are used in the treatment of asthma. The aim of this
      study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma
      treatments. METHODS: A mouse model of chronic asthma was developed. The
      fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups
      were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and
      histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses
      were applied. RESULTS: The cell concentration in the BAL fluid decreased in all
      the treatment groups. The rate of perivascular and peribronchial cell
      infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups.
      Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and
      anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the
      fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high
      dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in
      the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level
      increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level
      decreased in the BAL fluid in the anti-TNF group. The relative expression of
      miRNA-126 increased in all groups. The relative expression of miRNA-133a
      decreased in the placebo and fluticasone groups. The relative expression of miRNA
      133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE
      and anti-TNF groups. CONCLUSIONS: The results showed that anti-IgE is successful
      as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to
      other therapeutic modalities when used for prophylaxis.

PMID- 29191363
TI  - Histopathological proof of the pathogenicity of a rare GFAP mutation in a patient
      with flaccid paraparesis.
AB  - Infantile Alexander disease is a rare progressive leukodystrophy caused by
      autosomal dominant mutations in the (GFAP) gene typically presenting with
      psychomotor retardation, progressive macrocephaly and refractory epilepsy.
      Neuroradiological hallmarks are extensive white matter lesions with frontal
      preponderance as well as signal intensity changes of basal ganglia and medulla
      oblongata with variable contrast enhancement. Here, we report an atypical
      manifestation in a 21-month-old boy presenting with flaccid paraparesis and
      areflexia. Cognitive, visual as well as fine motor skills and muscular strength
      of the upper extremities were appropriate for age. Weight and height as well as
      head circumference were within normal range. Clinical or electroencephalographic
      signs of seizures were absent. Cranial MRI demonstrated bifrontal cystic tumorous
      lesions with partial contrast rims, as well as space-occupying focal lesions of
      the caudate nuclei. Spinal MRI revealed swelling of the lumbar and cervical
      spinal cord. CSF and blood chemistry showed normal results. Histopathology of a
      subcortical lesion showed large amounts of Rosenthal fibers and protein droplets
      characteristic of Alexander disease. Sequencing detected a heterozygous mutation
      of the GFAP gene (c.205G > A; p.(Glu69Lys)) that has been reported before as
      probably pathogenetic in another case of lower spinal involvement. This well
      documented case draws attention to atypical spinal manifestations of Alexander
      disease and gives histopathological proof of the pathogenetic role of a rare GFAP
      mutation with marked spinal involvement.

PMID- 29191365
TI  - Trainee Knowledge of Imaging Appropriateness and Safety: Results of a Series of
      Surveys From a Large Academic Medical Center.
AB  - OBJECTIVE: In order to provide high quality care to their patients and utilize
      imaging most judiciously, physician trainees should possess a working knowledge
      of appropriate use, radiation dose, and safety. Prior work has suggested
      knowledge gaps in similar areas. We aimed to evaluate the knowledge of imaging
      appropriateness, radiation dose, and MRI and contrast safety of physician
      trainees across a variety of specialties. METHODS: Between May 2016 and January
      2017, three online surveys were distributed to all interns, residents, and
      fellows in ACGME accredited training programs at a large academic institution
      over two academic years. RESULTS: Response rates to three surveys ranged from
      17.2% (218 of 1266) for MRI and contrast material safety, 19.1% (242 of 1266) for
      imaging appropriateness, to19.9% (246 of 1238) for radiation dose. Overall 72%
      (509 of 706) of survey respondents reported regularly ordering diagnostic imaging
      examinations, but fewer than half (47.8%; 470 of 984) could correctly estimate
      radiation dose across four commonly performed imaging studies. Only one third
      (34%; 167 of 488) of trainees chose appropriate imaging in scenarios involving
      pregnant patients. Trainee post-graduate year was not significantly correlated
      with overall radiation safety scores, and no significant difference was found
      between radiation safety or appropriate imaging scores of those who participated
      in a medical school radiology elective vs. those who did not. A total of 84% (57
      of 68) of radiology trainees and 43% (269 of 630) of non-radiology trainees
      considered their knowledge adequate but that correlated only weakly correlated to
      actual knowledge scores (p<0.001). Most trainees (73%, 518 of 706) agreed that
      more training in these areas would have beneficial effects on patient care.
      CONCLUSIONS: Knowledge gaps pertaining to appropriateness and imaging safety
      exist among many trainees. In order to enhance the value of imaging at the
      population level, further work is needed to assess the most appropriate method
      and stage of training to address these knowledge gaps.

PMID- 29191364
TI  - An improved system for grading and treating tinnitus.
AB  - OBJECTIVE: Tinnitus is an auditory sensation that can cause discomfort or even
      pain. Because patients with tinnitus frequently have psychological problems, self
      reporting of the severity of tinnitus is unreliable. We developed a new grading
      system and practical protocol for the systematic treatment of tinnitus that
      accounts for its severity, patients' psychological problems, and the frequency of
      catastrophic episodes. The aim of this study is to employ and validate the new
      system in patients with tinnitus. METHODS: This study comprised two parts: (i) We
      identified 113 patients, who were then analyzed in terms of severity of tinnitus,
      psychological problems, and catastrophic episodes. They were then classified into
      5 grades, and the records of their previous treatments were scrutinized. From
      these records, we designed a practical treatment protocol suitable for each of
      the 5 grades. (ii) We then identified 82 new patients, and graded and treated
      them according to the system developed in part (i). Patients were followed-up for
      at least 6 months; treatment efficacy was evaluated using the pre- and post
      treatment scores on the Tinnitus Handicap Inventory (THI) and Hospital Anxiety
      and Depression Scale (HADS). Psychological status was also assessed with the DSM
      IV. RESULTS: (i) The overall patient group was categorized as follows: Grade I,
      38 patients, average THI=37.6 points, average HADS=10.9 points, catastrophic
      episodes=0 points; Grade II, 24 patients, THI=70.6, HADS=13.1, catastrophic
      episodes=0; Grade III, 5 patients, THI=73.2, HADS=28.4, catastrophic episodes=0;
      Grade IV, 33 patients, THI=63.5, HADS=18.8, catastrophic episodes=1.0; Grade V,
      13 patients, THI=73.2, HADS=22.4, catastrophic episodes=2.2. The treatment
      records revealed treatment via psychotropic drugs for 40% of Grade III, 45.5% of
      Grade IV, and 84.6% of Grade V patients; psychiatric consultation was provided
      for 20% of Grade III, 12.5% of Grade IV, and 53.8% of Grade V patients. (ii) THI
      scores improved significantly in Grades II, IV, and V after treatment using the
      new protocol; HADS scores improved significantly in Grades IV and V. Catastrophic
      episode scores improved significantly in Grades IV and V. CONCLUSION: We found
      large enough differences in THI and HADS scores to successfully classify patients
      with tinnitus into 5 distinct grades that accounted for tinnitus severity,
      psychological problems, and catastrophic episodes. We found significant
      improvements in tinnitus severity and psychological problems in the higher (more
      severe) grades when this system was used to guide treatment. This system not only
      provided a reasonably reliable categorization system, it simplified treatment
      without sacrificing efficacy.

PMID- 29191366
TI  - Cell-Autonomous Metabolic Reprogramming in Hypoxia.
AB  - Molecular oxygen (O2) is a universal electron acceptor that enables ATP synthesis
      through mitochondrial respiration in all metazoans. Consequently, hypoxia (low
      O2) has arisen as an organizing principle for cellular evolution, metabolism, and
      (patho)biology, eliciting a remarkable panoply of metabolic adaptations that
      trigger transcriptional, translational, post-translational, and epigenetic
      responses to determine cellular fitness. In this review we summarize current and
      emerging cell-autonomous molecular mechanisms that induce hypoxic metabolic
      reprogramming in health and disease.

PMID- 29191367
TI  - Heterotypic Ubiquitin Chains: Seeing is Believing.
AB  - The biological diversity of ubiquitination resides in the multivalent nature of
      linkage-specific homotypic and heterotypic ubiquitin (Ub) chains. A recent
      publication by Yau et al. in Cell describes the development of K11/K48-bispecific
      antibodies and a physiological role for K11/K48 heterotypic chains in regulation
      of the cell cycle and clearance of aggregated proteins.

PMID- 29191368
TI  - A novel homozygous nonsense mutation in NEFL causes autosomal recessive Charcot
      Marie-Tooth disease.
AB  - The neurofilament light polypeptide (NEFL) gene mutations cause mainly autosomal
      dominant Charcot-Marie-Tooth disease (CMT) and rarely the recessive forms of CMT.
      We describe a 13-year-old girl born of consanguineous parents. She presented an
      early onset of gait disturbance with weakness in lower extremities during the
      first decade. Nerve conduction velocity of median nerve was 24 m/s and amplitude
      of compound muscle action potential was 2.2 mV. Sensory nerve action potential
      was not recordable. Sural nerve biopsy showed severe loss of the large myelinated
      fibers. Electron microscopy revealed absence of neurofilaments in both myelinated
      and unmyelinated axons. Genetic analysis identified a novel homozygous nonsense
      mutation in NEFL c.487G>T (p.Glu163*) as the potential causative mutation in this
      patient. Our study expands the mutation spectrum of NEFL-related neuropathy.

PMID- 29191370
TI  - LINC complexes and nuclear positioning.
AB  - One of the characteristics of eukaryotic cells is their structural plasticity
      associated with the ability to carry out a broad range of complex functions, both
      autonomously and as components of tissues and organs. Major cellular
      rearrangements can be observed in various systems from meiosis in fission yeast,
      through dermal differentiation in nematodes, to muscle and neuronal development
      in vertebrates. Each of these processes involves oftentimes dramatic relocation
      of the nucleus within the cell. During the last decade it has become apparent
      that the nuclear periphery represents a nexus of cytoskeletal interactions that
      are involved not only in nuclear movement but also in the distribution and
      dissemination of mechanical forces throughout the cell. Nucleocytoskeletal
      coupling is mediated in large part by SUN- and KASH-domain proteins of the
      nuclear membranes, that together assemble to form LINC (Linker of the
      Nucleoskeleton and Cytoskeleton) complexes. In this review we will describe how
      the LINC complex repertoire contributes to nuclear positioning and chromosome
      dynamics in a variety of cellular contexts.

PMID- 29191369
TI  - Effect of drying, composting and subsequent impurity removal by sieving on the
      properties of digestates from municipal organic waste.
AB  - The application of organic soil amendments is a common measure to prevent
      structural degradation of agricultural soils and to maintain and improve long
      term soil fertility. Solid residues from anaerobic digestion of municipal organic
      waste (MOW) are rich in nutrients and organic matter and have a promising
      potential to be used as soil amendment. However, no study has related amendment
      properties of MOW digestate of one origin to different treatment procedures. We
      therefore investigated the impact of drying, composting and sieving on final
      digestate properties and specifically nutrient availability and heavy metal and
      carbon elution. Samples were provided by a semi-industrial two-stage biogas plant
      with dry fermentation of MOW. Results confirm that in comparison to drying,
      composting of MOW digestates leads to a significant increase of K, P, Mg, Ca, Cd
      and Cr in the digestates. Sieving of composted digestates showed that heavy
      metals are not evenly distributed and that heavy metal concentration in the
      digestate increases with decreasing mesh sizes (highest concentrations in the
      fractions <1 mm). Although the element concentration is higher in composted
      batches, the water-extractability of nutrients, heavy metals and carbon is
      significantly lower from composted over dried digestates. A significant
      correlation was found between the dissolution of Zn, Ni, Ca and Mg and pH of
      eluate as well as dissolved organic carbon (DOC) release (R > 0.7, p<0.05).
      Results confirm that the extent of carbon elution depends on the degradation rate
      of digestates. DOC may therefore be a good measure to evaluate digestate
      stability and to decide on treatment measures.

PMID- 29191371
TI  - Rat-bite fever due to Streptobacillus notomytis isolated from a human specimen.
AB  - Rat-bite fever (RBF) is a disease that usually presents with fever, arthralgia
      and skin rash. Streptobacillus moniliformis was considered the main cause of RBF
      among the genus Streptobacillus. Although with similar clinical presentation, RBF
      due to Streptobacillus notomytis is unusual in humans. To the best of our
      knowledge, we present a case involving the first isolate of S. notomytis in
      humans. A 63-year-old woman was admitted to our hospital with fever, rash and
      polyarthritis. She recalled being bitten by a rat on her finger 5 days before
      presentation. Clinical manifestations were compatible with rat-bite fever (RBF)
      and the diagnosis was confirmed by the detection of Streptobacillus species from
      both blood and pustule samples. Initial polymerase chain reaction tests revealed
      that the organism was S. moniliformis. However, thorough genetic analysis
      revealed the organism to be S. notomytis. The condition was successfully treated
      with ampicillin.

PMID- 29191372
TI  - Th1-related disease development during omalizumab treatment: Two cases with
      severe asthma.

PMID- 29191373
TI  - The mental health of refugees and asylum seekers on Manus Island.

PMID- 29191374
TI  - [Involuntary psychiatric care for inmates in France: Only for "dangerous"
      patients?]
AB  - The unites hospitalieres specialement amenagees (UHSA) are full-time inpatient
      psychiatric units for inmates in France. Their creation has been associated with
      several advances in access to psychiatric care for inmates in recent years.
      However, there is still only one means of involuntary hospitalization for
      prisoners in France: care by decision of a representative of the state (les soins
      sur decision d'un representant de l'etat [SDRE]). Interestingly, for SDRE to be
      recognized as legal by the French judge, the patient must be "a danger to himself
      or to the others". Thus, there is a major difference with involuntary
      hospitalization outside the prison, and there are specific criteria for
      involuntary psychiatric hospitalization for inmates in France. This situation
      questions the general framework of involuntary psychiatric care and is very
      inconsistent with French law. Indeed, the goal of the loi no 94-43 du 18 janvier
      1994 relating to public health and social protection is to ensure equivalent care
      for all patients, incarcerated or not.

PMID- 29191375
TI  - Rheumatologic symptoms in oncologic patients on PD-1 inhibitors.
AB  - OBJECTIVE: Immune checkpoint inhibitors are effective cancer therapies that have
      been associated with immune-related adverse events (irAEs). Recent reports of
      irAEs describe symptoms resembling classic rheumatologic syndromes, most notably
      associated with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor
      blockade. Though cases have been described, there are fewer reports of
      rheumatologic disease associated with programmed cell death protein-1 (PD-1)
      inhibitors. Here, we describe a series of four patients presenting to the Brigham
      and Women's Hospital (BWH) Arthritis Center with de novo polymyalgia rheumatica
      (PMR)-type conditions and/or peripheral synovitis after treatment with PD-1/PD
      Ligand 1 (PD-L1) pathway inhibitors. METHODS: Patients with metastatic renal cell
      carcinoma (RCC) who were treated with PD-1/PD-L1 pathway inhibitors and
      subsequently developed complaints of new joint pain were referred to the BWH
      Arthritis Center as part of routine care and identified retrospectively. The
      electronic medical record was reviewed for cancer history and treatment,
      rheumatologic symptoms, physical exam, laboratory testing, and clinical course.
      RESULTS: All four patients developed irAEs consistent with a PMR-type syndrome
      and/or peripheral synovitis. Symptoms persisted despite discontinuation of the PD
      1/PD-L1 pathway inhibitors; however, three of the patients responded well to oral
      glucocorticoids alone while one patient required the addition of oral
      methotrexate. All patients had an eventual decline in inflammatory markers.
      CONCLUSION: These cases highlight the need for both oncologists and
      rheumatologists to recognize the development of rheumatologic disease during
      treatment with immune checkpoint blockade. Further investigation is needed to
      optimize the management of irAEs, particularly considering the increasing use of
      checkpoint inhibitors to treat malignancies.

PMID- 29191376
TI  - Clinical, histological, immunological presentations and outcomes of bullous
      systemic lupus erythematosus: 10 New cases and a literature review of 118 cases.
AB  - BACKGROUND: Bullous systemic lupus erythematosus (BSLE) is a rare blistering
      condition associated with systemic lupus erythematosus (SLE). PATIENTS AND
      METHODS: We conducted a multi-center retrospective study and literature review in
      order to describe the clinical, immunological, and histological presentations and
      outcomes of BSLE. The skin biopsies were centrally reviewed, and sera obtained
      during a flare of BSLE were analyzed for identification of circulating anti
      basement membrane zone antibodies. RESULTS: Ten patients (all women, median age
      at SLE diagnosis of 22 years) were included, as well as 118 cases from a
      systematic review of the literature. Lupus nephritis was associated in 50% of the
      cases. BSLE presented as tensed bullae on normal or erythematous skin,
      predominantly localized on the trunk, arms, head, and neck. Urticarial lesions
      were associated in 31% of the cases, and mucous membrane involvement was seen in
      51%. Histological analyses displayed subepidermal detachment, dermal infiltration
      of polynuclear neutrophils, alignment of these cells at the basal membrane zone
      and leukocytoclasis. The direct immunofluorescence was polymorphic, showing
      linear and/or granular deposits of IgG, IgA, IgM, and/or C3. Anti-type VII
      collagen antibodies were detected in 69% of cases. Dapsone was efficacious in 90%
      of cases. CONCLUSION: BSLE is rather an autoimmune neutrophilic blistering
      disease associated with SLE than a cutaneous manifestation and may be associated
      with active extra-cutaneous manifestations of SLE. Dapsone is the first-choice
      option.

PMID- 29191377
TI  - Distally based sural neuro-fasciocutaneous perforator flap for foot and ankle
      reconstruction: Surgical modifications for flap pedicle and donor site closure
      without skin graft.
AB  - BACKGROUND: The conventional procedure of the sural neuro-fasciocutaneous flap
      enables the supply of blood and venous drainage by increasing the width of the
      adipofascial tissue and preserving tiny venous return routes. Moreover, skin
      graft is a common method for donor site closure, which may lead to some
      complications and influence the aesthetic appearance. We report modifications for
      a distally based sural neuro-fasciocutaneous perforator flap and a relaying flap
      for donor site closure without skin graft. METHODS: Twelve patients undergoing
      the modified flap for foot and ankle reconstruction were included in this study
      between 2014 and 2016. A peroneal-based perforator, a superficial vein, and the
      vascular axis of the sural nerve were included in the pedicle. A Z-shape skin
      incision was performed to explore the perforator vessels and a relaying island
      perforator flap was used to close the donor site. RESULTS: All flaps survived
      completely without necrosis. The area of the flaps ranged from 16 * 8 cm to 30 *
      15 cm. The diameter width of the pedicle ranged from 1.0 to 2.0 cm. A relaying
      perforator island flap was used in 10 cases for donor site closure and no skin
      graft was performed. There were no serious donor site complications. All patients
      were satisfied with the aesthetic outcome postoperatively at the final follow-up.
      CONCLUSIONS: The distally based sural neuro-fasciocutaneous perforator flap is
      considered a reliable method for foot and ankle reconstruction. The modification
      for flap pedicle and donor site closure method without skin graft should be
      recommended.

PMID- 29191378
TI  - Patients with head trauma: A study on initial prehospital assessment and care.
AB  - BACKGROUND: Best evidence guidelines are intended to standardise assessment and
      treatment of patients with head trauma and improve outcomes for TBI patients. The
      primary aim was to explore pre-hospital emergency care nurses' (PECNs')
      documented assessment and care of patients with head trauma and the secondary aim
      to study gender differences in the documented care and interventions given by the
      PECNs. METHODS: A retrospective observational study was conducted by evaluating
      2750 prehospital medical records. RESULTS: The results showed that 25.2% of the
      patients were assessed according to all four core-elements in the guidelines and
      78.6% of the patients underwent at least one intervention by the PECNs. Male
      patients were to a higher extent assessed according to guidelines and were given
      higher transport priority while females were more often assessed for vital
      parameters and received significantly more analgesics. The assessment documented
      by the PECNs was not optimal concerning documentation using the Glasgow Coma
      Scale, but the documented assessment of circulation and, especially, respiratory
      rate was high (77.2%) compared to previous studies. CONCLUSION: The findings of
      this study showed a low degree of documented assessment of parameters related to
      head trauma and might also indicate some gender differences in the assessment and
      management.

PMID- 29191379
TI  - Clinical outcome of patients with suicide attempts: 1098 patients.

PMID- 29191380
TI  - Benign recurrent intrahepatic cholestasis (BRIC)-like episode associated with
      ATP8B1 variation underlying protracted cholestatic course of acute hepatitis E
      virus infection.

PMID- 29191381
TI  - Editorial Comment.

PMID- 29191382
TI  - Reply.

PMID- 29191383
TI  - Growth and development in school-age children from Rostov region, Russia:
      Comparison between urban and rural settings.
AB  - The purposes of the current study were: (1) to describe growth and physical
      development and establish norms for schoolchildren from Rostov region in Russia;
      (2) to compare major characteristics of development between urban and rural
      children by sex and age. Nearly 200,000 children (198,712) aged between 7 and 17
      years from 232 urban and rural schools of Rostov region (Southern Federal
      District of Russia) participated in the study. School age is a period of
      intensive growth and physiological and psychological development. Irregularities
      of personal development are caused by a multitude of factors, such as sex
      differences, heredity, socio-economic status of a family, standard of living,
      particular environmental conditions, and lifestyle. It has been established that
      children from the Southern Federal District of Russia had body mass index values
      higher than age-appropriate norms for all Russians (Total Russian, Rudnev et al.,
      2014) and World Health Organization charts. Children from urban settings were
      taller and heavier than children from rural settings. Sex is one of the most
      influential factors which play key role in determining specific characteristics
      of growth and personal development. According to our results, boys and girls both
      had similar age-related changes in weight and height, but their respective
      dynamics differed. Girls' height and weight values accelerated at the age 10 to
      12 years and plateaued after the age fourteen, whereas in boys height and weight
      steadily increased with age, showing slight acceleration at the age 12 to 13
      years, and reached a plateau by the age of seventeen.

PMID- 29191384
TI  - The effect of bioresorbable vascular scaffold implantation on distal coronary
      endothelial function in dyslipidemic swine with and without diabetes.
AB  - BACKGROUND: We studied the effect of bioresorbable vascular scaffold (BVS)
      implantation on distal coronary endothelial function, in swine on a high fat diet
      without (HFD) or with diabetes (DM+HFD). METHODS: Five DM+HFD and five HFD swine
      underwent BVS implantation on top of coronary plaques, and were studied six
      months later. Conduit artery segments >5mm proximal and distal to the scaffold
      and corresponding segments of non-scaffolded coronary arteries, and segments of
      small arteries within the flow-territory of scaffolded and non-scaffolded
      arteries were harvested for in vitro vasoreactivity studies. RESULTS: Conduit
      segments proximal and distal of the BVS edges showed reduced endothelium
      dependent vasodilation as compared to control vessels (p<=0.01), with distal
      segments being most prominently affected(p<=0.01). Endothelial dysfunction was
      only observed in DM+/-HFD swine and was principally due to a loss of NO.
      Endothelium-independent vasodilation and vasoconstriction were unaffected.
      Surprisingly, segments from the microcirculation distal to the BVS showed
      enhanced endothelium-dependent vasodilation (p<0.01), whereas endothelium
      independent vasodilation and vasoconstriction were unaltered. This enhanced
      vasorelaxation was only observed in DM+HFD swine, and did not appear to be either
      NO- or EDHF-mediated. CONCLUSIONS: Six months of BVS implantation in DM+HFD swine
      causes NO-mediated endothelial dysfunction in nearby coronary segments, which is
      accompanied by a, possibly compensatory, increase in endothelial function of the
      distal microcirculation. Endothelial dysfunction extending into coronary conduit
      segments beyond the implantation-site, is in agreement with recent reports
      expressing concern for late scaffold thrombosis and of early BVS failure in
      diabetic patients.

PMID- 29191385
TI  - Hydrophilic modified magnetic multi-walled carbon nanotube for dispersive
      solid/liquid phase microextraction of sunitinib in human samples.
AB  - In this paper, a novel approach for the efficient microextraction and
      determination of anticancer drug, sunitinib from human samples is described. We
      synthesized a new nanocomposite; honey coated magnetic multi-walled carbon
      nanotubes (Honey@magnetic-CNTs). This nanocomposite retains the magnetic
      properties of individual magnetic nanoparticles (MNPs) and can be effectively
      separated under an external magnetic field. The synthesized nanoparticles were
      characterized by FT-IR, VSM, EDAX and XRD and TEM studies. The spherical
      particles obtained before and after the functionalization had sizes of 14 nm and
      16 nm, respectively. The method is based on Honey@magnetic-CNTs assisted
      dispersive solid-liquid phase microextraction for determination and analysis of
      the drug. The influences of experimental parameters were investigated. Under
      optimal conditions, the applied nanocomposite showed good performance, high
      sensitivity and fast extraction of the analyte from biological samples. In
      linearity test, the regression correlation coefficient was obtained more than 99%
      for analyte of interest and linear dynamic range for the proposed method was from
      5 to 5000 ng mL-1. Method detection and quantification limits were 1.58 ng mL-1
      and 5.28 ng mL-1, respectively. Relative standard deviation was 3.15%.

PMID- 29191386
TI  - MiR-429 regulates the metastasis and EMT of HCC cells through targeting RAB23.
AB  - Accumulating documents have revealed that microRNAs (miRNAs) play critical roles
      in the development and progression of tumors. MiR-429 has been reported to be
      involved in regulating various cellular processes. However, its biological role
      and underlying mechanism in hepatocellular carcinoma (HCC) still need to be
      further studied. The present study aimed to investigate the function of miR-429
      in the progression of HCC. In terms of this paper, it was found that miR-429 was
      down-regulated in HCC tissues and cells. After being transfected with miR-429
      mimics, miR-429 decreased the migratory capacity and reversed the EMT to MET in
      HCC cells. RAB23 was confirmed as a target of miR-429. Rescue assays further
      verified that the function of miR-429 in HCC cells was exerted through targeting
      RAB23. In general, it was concluded that the signal pathway miR-429/RAB23 might
      be a potential target for HCC treatment.

PMID- 29191387
TI  - Knowledge translation in tri-sectoral collaborations: An exploration of
      perceptions of academia, industry and healthcare collaborations in innovation
      adoption.
AB  - With the aging population and increase in chronic disease conditions, innovation
      to transform treatment pathways and service delivery will be necessary. The
      innovation adoption process however, can take 15 years before widespread adoption
      occurs in most healthcare systems. Current UK government policies to increase the
      facilitation of innovation adoption are under way. The aim of this study is to
      explore perceptions of tri-sectoral collaborations in the healthcare sector. The
      data in the study are drawn from a cross-sectional survey conducted in 2015 of
      professionals in academia, industry and the healthcare sectors in England,
      focusing on Diabetes care. Academia and healthcare respondents had the least work
      experience outside of their sectors compared to the industry respondents.
      Healthcare and academia respondents rated the industry sector less trustworthy,
      unethical, having different goals and less understanding of the other sectors.
      Industry respondents had a more positive perspective towards potential
      collaborators. The results from the study demonstrate greater potential
      challenges to tri-sectoral collaborations and the government's knowledge
      translation policy, due to pre-conceived notions and lack of understanding of
      other sectors. The purely structural approach of establishing government mandated
      translational networks may be insufficient without active attempts to improve
      collaborative relationships. Mechanisms to facilitate trust building and
      collaboration are proposed.

PMID- 29191388
TI  - Tracing the evolution of venom phospholipases A2 in Gloydius strauchii and
      related pitvipers: A tale of two acidic isozymes.
AB  - Two acidic Asp49-PLA2s with Glu6 substitution and a neutral Lys49-PLA (designated
      Gst-K49) were cloned from G. strauchii venom glands, their full amino acid
      sequences were deduced. The predominant acidic PLA2 (designated Gst-E6a) contains
      124 residues and the M18W30 substitutions, while the minor acidic PLA2
      (designated Gst-E6b) contains 122 residues and the V18A30 substitutions. Their
      sequences are most similar to those of the respective orthologous PLA2s of G.
      intermedius venom. Gst-E6a and Gst-E6b appear to be paralogs and possibly have
      different predatory targets or functions. The LC-MS/MS results indicate the
      presence of only three PLA2 gene products in the crude venom, the relative
      expression levels were in the order of Gst-E6a ? Gst-E6b > Gst-K49, as confirmed
      by qPCR results. In contrast to other Gloydius, G. strauchii venom does not
      contain neurotoxic or basic anticoagulant Asp49-PLA2s, but Gst-K49 is the first
      Lys49-PLA2 identified in Gloydius venoms. However, its venom content is
      relatively low and its pI value 7.3 is much lower than those of other Lys49-PLA2s
      and. The Lys49-PLA2 genes appear to regress in the venom of most of Gloydius and
      related rattlesnake, and this evolutionary regression occurred before the
      dispersal of Asian pitvipers to the New World.

PMID- 29191389
TI  - Challenges faced by the Japanese Orthopaedic Association in the treatment and
      prevention of locomotive organ disorders in the era of "super-ageing".

PMID- 29191390
TI  - Efficacy of intraoperative lumbar subarachnoid drainage for prevention of
      cerebrospinal fluid leak after spinal cord tumor resection.
AB  - BACKGROUND: Postoperative cerebrospinal fluid (CSF) leakage is a major clinical
      problem, and prevention of CSF leakage at the surgical site is an important
      issue. The goal of the study was to evaluate the efficacy of intraoperative
      lumbar subarachnoid drainage (LSAD) for prevention of CSF leakage after spinal
      cord tumor resection. METHODS: The subjects were 97 patients with a cervical or
      thoracic primary intradural spinal cord tumor who underwent surgery at our
      hospital. A LSAD catheter was placed in the lumbar thecal sac before incision and
      left in place for several days postoperatively. Age, tumor level, number of
      laminectomy levels, operation time, estimated blood loss (EBL) intraoperatively,
      use of artificial dura mater, white blood cell (WBC) counts and C-reactive
      protein (CRP) levels on postoperative days (PODs) 3 and 10, subcutaneous CSF
      accumulation at the operation site, and postoperative complications were examined
      retrospectively. RESULTS: LSAD of CSF was performed in 35 patients. In this
      group, the drainage catheter was left in place for an average of 4.9 (range 3-8)
      days. Use of artificial dura mater was significantly higher and CRP on POD 10 was
      significantly lower in the drainage group. Subcutaneous accumulation of CSF due
      to leakage was significantly higher in patients with cervical lesions than in
      those with thoracic lesions. In cases in which artificial dura mater was used,
      CSF leakage occurred at a significantly lower rate in the drainage group. Without
      use of an artificial dura mater, CSF leakage did not differ significantly between
      the two groups. CONCLUSION: Lumbar subarachnoid CSF drainage was associated with
      a significant decrease in postoperative CRP. In cases in which artificial dura
      mater was used and in surgery for a cervical lesion, drainage was useful to
      prevent subcutaneous CSF accumulation.

PMID- 29191391
TI  - Biphasic lung injury during Streptococcus pneumoniae infection in a murine model.
AB  - OBJECTIVES: Streptococcus pneumoniae is the leading cause of community-acquired
      pneumonia. We aimed to analyze the epithelial response to S. pneumoniae-induced
      lung injury. METHODS: Using an in vitro model with 16HBE cells and experimental
      in vivo murine model of acute lung injury, we analyzed the epithelial response to
      S. pneumoniae. Lung epithelial cell monolayers were exposed to S. pneumoniae and
      permeability was assessed by transepithelial resistance (TER) measurement and
      organization and expression of junction proteins. Functional consequences were
      studied with an in vivo murine model measuring alveolar permeability, distal
      alveolar fluid clearance (DAFC), and the alveolar inflammatory response. RESULTS:
      In vitro, S. pneumoniae induced a dose-dependent decrease in transepithelial
      resistance, which was associated with significant modifications in the
      organization of junction proteins assessed by immunofluorescence staining and
      expression after 6hours of exposure. In vivo, S. pneumoniae induced a transient
      increase in alveolar permeability with an adequate increase in DAFC 6hours post
      infection. In a second phase, a permanent increased permeability was associated
      with a major decrease in DAFC. CONCLUSION: Overall, the epithelial response to S.
      pneumoniae followed a biphasic pattern with an initial reversible increase in
      permeability related to the alteration of tight and adherens junctions and a
      second phase associated with an epithelial injury with a major increase in
      permeability with a decreased DAFC reflecting an injured alveolar capillary
      barrier.

PMID- 29191392
TI  - Cold atmospheric plasma (CAP) activates angiogenesis-related molecules in skin
      keratinocytes, fibroblasts and endothelial cells and improves wound angiogenesis
      in an autocrine and paracrine mode.
AB  - BACKGROUND: Cold atmospheric plasma (CAP) emerged as a novel therapeutic field
      with applications developed for bacterial sterilization, wound healing and cancer
      treatment. For clinical implementation it is important to know how CAP works and
      which molecular changes occur after the CAP treatment. Vascularization is an
      important step during wound healing, however, the effects of CAP on wound
      angiogenesis are not well examined so far. Furthermore, it has not been
      investigated, whether CAP primarily affects endothelial cells directly or via
      paracrine mechanisms to modulate the vasculature. OBJECTIVE: This study
      concentrates on the influence of CAP on angiogenesis-related molecules in human
      epidermal keratinocytes, dermal fibroblasts and endothelial cells. METHODS: CAP
      was generated by the MicroPlaSter beta(r) plasma torch system and CAP effects on
      angiogenesis were determined in vitro and in vivo. RESULTS: We observed that CAP
      significantly induces the expression of Artemin, EGF, EG-VEGF (PK1), Endothelin-1
      (ET-1), FGF-2 (FGF basic), IL-8 (CXCL8) and uPA in keratinocytes and Angiogenin
      (ANG), Endostatin (Col18A1), MCP-1 (CCL2), MMP-9, TIMP-1, uPA and VEGF in
      fibroblasts. In addition, CAP activates the expression of Angiopoietin-2 (Ang-2),
      Angiostatin (PLG), Amphiregulin (AR), Endostatin, FGF-2 and angiogenic-involved
      receptor expression of FGF R1 and VEGF R1 in HUVEC endothelial cells. It was also
      demonstrated that supernatants collected from CAP activated fibroblasts and
      keratinocytes elevate tube formation by endothelial cells and FGF-2 appears to be
      an important pro-angiogenic factor that controls vascularization via paracrine
      mechanisms. Mouse experiments supplement that CAP promotes angiogenesis during
      wound healing in vivo. CONCLUSIONS: Taken together, these results suggest that
      CAP modulates angiogenesis-involved factors via autocrine and paracrine
      mechanisms and may be used to affect angiogenesis during wound healing.

PMID- 29191393
TI  - A novel anti-melanogenic agent, KDZ-001, inhibits tyrosinase enzymatic activity.
AB  - BACKGROUND: The demand for anti-melanogenic agents is increasing due to the
      unwanted side effects of current treatments. To find an effective anti
      melanogenic agent, we used zebrafish as a whole animal model for phenotype-based
      drug and cosmetic discovery screening. OBJECTIVES: The aim of this study was to
      identify and explore a small molecule that could be used for skin-whitening
      cosmetics. METHODS: Using zebrafish embryos, we examined the effects of 1000
      compounds on zebrafish development and pigmentation. Pigmentation production was
      assessed by tyrosinase (TYR) enzymatic activity and melanin contents.
      Pigmentation marker expression in the human melanoma cell line HMV-II was
      analyzed by western blot. We also tested reconstituted human skin tissue and
      analyzed KDZ-001 with computational molecular modeling. RESULTS: We identified
      three compounds that affected the pigmentation of developing melanophores in
      zebrafish. Among them, we identified KDZ-001, a novel anti-melanogenic agent,
      which strongly inhibits melanin synthesis in the developing melanophores of
      zebrafish, HMV-II cells, and reconstituted human skin with no toxicity. We found
      that KDZ-001 directly inhibits TYR enzymatic activity. Notably, computational
      molecular modeling of KDZ-001 suggested that its interaction with copper ions in
      the active site of TYR is essential for melanin synthesis, further demonstrating
      that KDZ-001 mainly acts as a TYR inhibitor to synthesize melanin. CONCLUSION:
      KDZ-001 inhibits melanin synthesis and has a potential for use in skin-whitening
      cosmetics.

PMID- 29191395
TI  - A novel cell-based high throughput assay to determine neutralizing antibody
      titers against circulating strains of rubella virus.
AB  - A large rubella outbreak occurred in Japan 2013, and 14,344 rubella and 45
      congenital rubella syndrome (CRS) cases were reported. At that time, the
      populational immunity was above the protective threshold assessed by
      hemmaglutination inhibition (HI) titer. The genotype 2B rubella virus (RV)
      strains were responsible for the outbreak, which are non-indigenous in Japan. In
      this work, a cell-based high throughput assay was established to measure the
      neutralizing antibody (NA) titer against circulating RV isolates. RV infection
      poorly induces cytopathic effects in tissue culture, preventing the casual
      measurement of NA titer. Our assay system has overcome this hurdle. Using this
      assay, we re-evaluated the antibody prevalence rate against circulating viral
      isolates using human sera collected before the outbreak. Individuals with
      protective IgG titer (>=10 IU/ml) represented 88.1% of the population.
      Consistently, 85.2% of the population had protective neutralizing antibody titers
      (>=1:8) against the vaccine strain. In contrast, 50.5% of the population had
      protective neutralizing antibody titers against circulating genotype 2B RV
      strains. These data suggest that the herd immunity assessed by HI titer should
      have been appreciated deliberately.

PMID- 29191396
TI  - Blood Lead Levels and Dental Caries in U.S. Children Who Do Not Drink Tap Water.
AB  - INTRODUCTION: This study's purpose is to determine whether nonconsumption of tap
      water is associated with lower prevalence of elevated blood lead levels and
      higher prevalence of dental caries in children and adolescents. METHODS: Cross
      sectional data from the National Health and Nutrition Examination Survey 2005
      2014 recorded drinking water source (n=15,604) and blood lead levels (n=12,373)
      for participants aged 2-19 years, and dental caries experience for the 2011-2014
      subset (n=5,677). The threshold for elevated blood lead level was >=3 MUg/dL. A
      binary outcome indicated presence or absence of dental caries experience.
      Multivariable generalized linear models estimated adjusted prevalence ratios with
      95% confidence limits. RESULTS: In analysis conducted in 2017, 15% of children
      and adolescents did not drink tap water, 3% had elevated blood lead levels >=3
      MUg/dL, and 50% had dental caries experience. Children and adolescents who did
      not drink water were less likely than tap water drinkers to have an elevated
      blood lead level (adjusted prevalence ratios=0.62, 95% confidence limits=0.42,
      0.90). Nonconsumers of tap water were more likely to have dental caries (adjusted
      prevalence ratios=1.13, 95% confidence limits=1.03, 1.23). Results persisted
      after adjustment for other covariates and using a higher threshold for elevated
      blood lead level. CONCLUSIONS: In this nationally representative U.S. survey,
      children and adolescents who did not drink tap water had lower prevalence of
      elevated blood lead levels and higher prevalence of dental caries than those who
      drank tap water.

PMID- 29191398
TI  - The Search for 'Evolution-Proof' Antibiotics.
AB  - The effectiveness of antibiotics has been widely compromised by the evolution of
      resistance among pathogenic bacteria. It would be restored by the development of
      antibiotics to which bacteria cannot evolve resistance. We first discuss two
      kinds of 'evolution-proof' antibiotic. The first comprises literally evolution
      proof antibiotics to which bacteria cannot become resistant by mutation or
      horizontal gene transfer. The second category comprises agents to which
      resistance may arise, but so rarely that it does not become epidemic. The
      likelihood that resistance to a novel agent will spread is evaluated here by a
      simple model that includes biological and therapeutic parameters governing the
      evolution of resistance within hosts and the transmission of resistant strains
      between hosts. This model leads to the conclusion that epidemic spread is
      unlikely if the frequency of mutations that confer resistance falls below a
      defined minimum value, and it identifies potential targets for intervention to
      prevent the evolution of resistance. Whether or not evolution-proof antibiotics
      are ever found, searching for them is likely to improve the deployment of new and
      existing agents by advancing our understanding of how resistance evolves.

PMID- 29191397
TI  - The inhibitory effect of Aconiti Sinomontani Radix extracts on the proliferation
      and migration of human synovial fibroblast cell line SW982.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aconiti Sinomontani Radix is frequently used in
      the treatment of Bi syndrome in traditional Chinese medicine. Several reports
      indicate that Aconiti Sinomontani Radix has therapeutic effects for rheumatoid
      arthritis (RA). However, the cellular mode of action is still unclear. To
      investigate the effect of alkaloid extracts of Aconiti Sinomontani Radix on
      proliferation and migration of human synovial sarcoma SW982 cells as well as the
      molecular mechanism underlying. MATERIALS AND METHODS: SW982 cells were examined
      for proliferation by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium
      bromide (MTT) method. Wound scratch assays were performed to assess the migrated
      rate of SW982 cells. Quantitative real-time PCR was used to measure the mRNA
      expression levels of Wnt5a, Runx2, MMP3, and Bmp2. Western blotting was used to
      measure the phosphorylated levels of JNK and NF-kappaB as well as the expression
      of MMP3. RESULTS: The alkaloid extract from Aconiti Sinomontani Radix (MQA) and
      MQB, which removed lappaconitine from MQA significantly inhibited the
      proliferation of SW982 in a dose-dependent manner. The proliferation inhibitory
      effect of MQB was more potent. Incubation with 10MUg/ml MQB for 12, 24, and 36h
      inhibited the migration of SW982 cells by 83%, 58%, and 42%, respectively.
      Treatment with different concentrations of MQB for 24h inhibited mRNA expression
      of Wnt5a, Runx2, and MMP3, but Bmp2 mRNA expression was elevated by MQB. Further,
      MQB inhibited phosphorylation of JNK and NF-kappaB p65 as well as MMP3 expression
      by Western blotting analysis. CONCLUSION: The results showed that MQB inhibited
      proliferation and migration of SW982 cells possibly through suppressing Wnt5a
      mediated JNK and NF-kappaB pathways. These results indicated that MQB might be an
      active extract of Aconiti Sinomontani Radix for targeting fibroblast-like
      synoviocytes (FLS) and be potential for RA therapy.

PMID- 29191399
TI  - From Axenic to Mixed Cultures: Technological Advances Accelerating a Paradigm
      Shift in Microbiology.
AB  - Since the onset of microbiology in the late 19th century, scientists have been
      growing microorganisms almost exclusively as pure cultures, resulting in a
      limited and biased view of the microbial world. Only a paradigm shift in
      cultivation techniques - from axenic to mixed cultures - can allow a full
      comprehension of the (chemical) communication of microorganisms, with profound
      consequences for natural product discovery, microbial ecology, symbiosis, and
      pathogenesis, to name a few areas. Three main technical advances during the last
      decade are fueling the realization of this revolution in microbiology:
      microfluidics, next-generation 3D-bioprinting, and single-cell metabolomics.
      These technological advances can be implemented for large-scale, systematic
      cocultivation studies involving three or more microorganisms. In this review, we
      present recent trends in microbiology tools and discuss how these can be employed
      to decode the chemical language that microorganisms use to communicate.

PMID- 29191394
TI  - Medications for alcohol use disorders: An overview.
AB  - Patients who suffer from alcohol use disorders (AUDs) usually go through various
      socio-behavioral and pathophysiological changes that take place in the brain and
      other organs. Recently, consumption of unhealthy food and excess alcohol along
      with a sedentary lifestyle has become a norm in both developed and developing
      countries. Despite the beneficial effects of moderate alcohol consumption,
      chronic and/or excessive alcohol intake is reported to negatively affect the
      brain, liver and other organs, resulting in cell death, organ damage/failure and
      death. The most effective therapy for alcoholism and alcohol related
      comorbidities is alcohol abstinence, however, chronic alcoholic patients cannot
      stop drinking alcohol. Therefore, targeted therapies are urgently needed to treat
      such populations. Patients who suffer from alcoholism and/or alcohol abuse
      experience harmful effects and changes that occur in the brain and other organs.
      Upon stopping alcohol consumption, alcoholic patients experience acute withdrawal
      symptoms followed by a protracted abstinence syndrome resulting in the risk of
      relapse to heavy drinking. For the past few decades, several drugs have been
      available for the treatment of AUDs. These drugs include medications to reduce or
      stop severe alcohol withdrawal symptoms during alcohol detoxification as well as
      recovery medications to reduce alcohol craving and support abstinence. However,
      there is no drug that completely antagonizes the adverse effects of excessive
      amounts of alcohol. This review summarizes the drugs which are available and
      approved by the FDA and their mechanisms of action as well as the medications
      that are under various phases of preclinical and clinical trials. In addition,
      the repurposing of the FDA approved drugs, such as anticonvulsants,
      antipsychotics, antidepressants and other medications, to prevent alcoholism and
      treat AUDs and their potential target mechanisms are summarized.

PMID- 29191400
TI  - [Primary care in Portugal].
AB  - The economic crisis and deterioration of the Portuguese National Health service
      has forced professionals to leave the country. The Portuguese National Health
      System was introduced in 1976, but it has been unable to provide citizens with
      the social and health advantages of an equality of access and free national
      health system. The Portuguese National Health System is financed by taxes.
      However, a 35% of its incomes are from private sources. The health minister
      decides the budget, and it is based on an historical financing plus a per capita
      system. Portuguese citizens and immigrants are entitled to free health care, but
      there is a co-payment for care, diagnostic, pharmacy, and emergency care. Health
      care provision is a mixture of public and private health care at a regional
      level. It leads to fragmentation of services and greater inequalities. Doctors
      are civil servants. Salary is regulated and it depends on seniority and on-call
      shifts. Primary care activities are similar to those of their Spanish
      counterparts. General practitioners have gatekeeper function, but the system is
      imperfect, and patients with private insurance get direct access to the
      specialist. Specialist training is similar to the training system in Spain.
      Continuing education is not regulated. The Portuguese Health System has been
      trying to become a national health system since 1979. Political instability,
      fragmentation of services, lack of clarity between public and private and co
      payments are important constraints. Inequalities are an important problem to
      reconsider while discussing a national health system.

PMID- 29191401
TI  - Comparative profiling of adrenal steroids in maternal and umbilical cord blood.
AB  - Fetal steroidome in late pregnancy receives multiple contributions from both
      maternal and fetal adrenals as well as from placenta. Depressed glucocorticoid
      levels have been reported in fetal blood at birth, yet studies on
      mineralocorticoid pathways are sparse. To investigate biosynthesis pathways at
      birth, adrenal steroids profiles were established in paired mothers and neonates.
      Forty-six paired healthy term newborns and their mothers from the Aldo cohort
      were assessed. Steroidomic profiles of mineralocorticoids, glucocorticoids and
      adrenal androgens were established from umbilical cord and maternal blood at
      birth using a highly sensitive and specific LC-MS/MS methodology. As compared to
      maternal blood, umbilical cord blood exhibited high levels of steroids precursors
      (progesterone and 11-deoxycorticosterone) contrasting with a collapse in
      corticosterone levels. Consecutively, 18-hydroxycorticosterone and aldosterone
      levels were also depressed in neonates. Similarly, umbilical cord blood levels of
      both 17-hydroxyprogesterone and 11-deoxycortisol were higher while cortisol
      levels sharply decreased. The product-to-substrate ratios evaluating the 11
      hydroxylation step (corticosterone/11-deoxycorticosterone and cortisol/11
      deoxycortisol) fell for both pathways. As expected, cortisone and 11
      dehydrocorticosterone levels exceed those of cortisol and corticosterone in
      umbilical cord blood reflecting the strong placental 11-beta-hydroxysteroid
      dehydrogenase type 2 (11betaHSD2) activity. Dehydroepiandrosterone-sulphate
      levels are higher in neonates, while both androstenedione and testosterone levels
      sharply fell. No significant difference in steroid levels could be observed
      according the gender except higher testosterone concentrations in umbilical cord
      of boys. Moreover, a strong and negative relationship between testosterone and
      progesterone levels was recorded in umbilical cord of boys. These adrenal
      steroidomic profiling demonstrate a deficit in mineralocorticoids (aldosterone,
      18-hydroxycorticosterone and corticosterone) and glucocorticoids (cortisol) in
      term neonates, reflecting either a relative defect in 11-hydroxylase activity or
      more likely the strong placental 11-beta-HSD2 activity. Collectively, these
      findings should be taken into account for a better understanding of regulatory
      interactions between placenta and fetal adrenal.

PMID- 29191404
TI  - High-resolution dynamic computer simulation of electrophoresis using a
      multiphysics software platform.
AB  - The modeling and simulation software COMSOL Multiphysics(r) was recently extended
      with an electrophoretic transport interface. Its performance was investigated by
      comparison to results obtained using the 1D dynamic electrophoresis simulators
      GENTRANS and SIMUL5. Simulations of zone electrophoresis, isotachophoresis,
      isoelectric focusing and of an oscillating electrolyte system were performed.
      Smooth profiles were essentially identical indicating that the COMSOL
      electrophoretic transport interface is able to reproduce results of the 1D
      simulators. Differences in the way the respective numerical schemes handle steep
      concentration gradients and associated instabilities were observed. The COMSOL
      electrophoretic transport interface is expected to be useful as a general model
      for simulations in 1D, 2D or 3D geometries, as well as for simulations combining
      electrophoresis with other physical phenomena.

PMID- 29191405
TI  - Hollow fiber membrane-protected molecularly imprinted microspheres for micro
      solid-phase extraction and clean-up of thiabendazole in citrus samples.
AB  - In the present work, molecularly imprinted polymer (MIP) microspheres were packed
      in polypropylene hollow fiber (HF) segments for the micro solid-phase extraction
      and clean-up of thiabendazole (TBZ) in citrus samples. Experimental parameters
      affecting TBZ extraction were carefully optimized. Hollow fiber membrane was able
      to protect MIP beads from solid matrix allowing the extraction and clean-up
      without the inclusion of further filtration and/or centrifugation steps. Under
      optimum experimental conditions, recoveries for TBZ at 0.83 mg kg-1 concentration
      level ranged from 5.1 to 6.1%, depending upon the sample analyzed (orange or
      lemon peel samples), with relative standard deviations (RSDs) lower than 4%. The
      limits of detection were 0.004 mg kg-1 in orange and 0.009 mg kg-1 in lemon, low
      enough for the determination of TBZ according to European Union legislation.

PMID- 29191403
TI  - Laminin-deficient muscular dystrophy: Molecular pathogenesis and structural
      repair strategies.
AB  - Laminins are large heterotrimers composed of the alpha, beta and gamma subunits
      with distinct tissue-specific and developmentally regulated expression patterns.
      The laminin-alpha2 subunit, encoded by the LAMA2 gene, is expressed in skeletal
      muscle, Schwann cells of the peripheral nerve and astrocytes and pericytes of the
      capillaries in the brain. Mutations in LAMA2 cause the most common type of
      congenital muscular dystrophies, called LAMA2 MD or MDC1A. The disorder manifests
      mostly as a muscular dystrophy but slowing of nerve conduction contributes to the
      disease. There are severe, non-ambulatory or milder, ambulatory variants, the
      latter resulting from reduced laminin-alpha2 expression and/or deficient laminin
      alpha2 function. Lm-211 (alpha2beta1gamma1) is responsible for initiating
      basement membrane assembly. This is primarily accomplished by anchorage of Lm-211
      to dystroglycan and alpha7beta1 integrin receptors, polymerization, and binding
      to nidogen and other structural components. In LAMA2 MD, Lm-411 replaces Lm-211;
      however, Lm-411 lacks the ability to polymerize and bind to receptors. This
      results in a weakened basement membrane leading to the disease. The possibility
      of introducing structural repair proteins that correct the underlying abnormality
      is an attractive therapeutic goal. Recent studies in mouse models for LAMA2 MD
      reveal that introduction of laminin-binding linker proteins that restore lost
      functional activities can substantially ameliorate the disease. This review
      discusses the underlying mechanism of this repair and compares this approach to
      other developing therapies employing pharmacological treatments.

PMID- 29191406
TI  - Enantioselective separation of racemates using CHIRALPAK IG amylose-based chiral
      stationary phase under normal standard, non-standard and reversed phase high
      performance liquid chromatography.
AB  - We have previously reported on the solvent versatility of immobilized amylose and
      cellulose-based chiral stationary phases in enantioselective liquid
      chromatographic separation of racemates. The studies were mainly focusing on the
      tris substituted 3,5-dimethylphenylcarbamate polysaccharide-based chiral
      stationary phases namely CHIRALPAK IA(r) [Amylose tris (3,5
      dimethylphenylcarbamate)] or ADMPC and CHIRALPAK IB(r) [Cellulose tris (3,5
      dimethylphenylcarbamate)] or CDMPC. Here we focus on the application of the
      recently introduced amylose tris (3-chloro-5-methylphenylcarbamate) or ACMPC and
      brand name CHIRALPAK IG(r) with a chlorine substituent replacing the methyl group
      in CHIRALPAK IA(r). This was investigated for the enantioslective separation of
      different classes of pharmaceuticals namely beta- and alpha-blockers, anti
      inflammatory and antifungal drugs, norepinephrine-dopamine reuptake inhibitor,
      catecholamines, sedative hypnotics, anti-histaminics, anticancer drugs,
      antiarrhythmic drugs, flavonoids, amino acids, alpha-2 adrenergic agonist,
      adrenaline and miscellaneous.A brief comparison between CHIRALPAK IG(r) and
      CHIRALPAK IA(r) under normal standard, non-standard and reversed mobile phase is
      demonstrated. The results revealed the versatility of the CHIRALPAK IG(r) column,
      its compatibility with a wide ranges of solvent and operation modes and its
      ability to separate chiral compounds not separated with other amylose based
      chiral stationary phases.

PMID- 29191407
TI  - Occupational outcomes following combat-related gunshot injury: Cohort study.
AB  - BACKGROUND: The long-term impact of gun violence on physical function and
      occupational disability remains poorly explored. We sought to examine the effect
      of combat-related gunshot injury on work capacity within a cohort of military
      servicemembers and identify clinical characteristics that influence the capacity
      to return to work. METHODS: A query was performed to identify all servicemembers
      injured by gunshot in the years 2005-2009. These soldiers were then followed for
      a period up to the end of 2014 in order to identify those separated from service
      due to an inability to perform military duties as a result of their injury. Socio
      demographic and clinical characteristics were considered co-variates. The
      dependent variable in this study was inability to effectively return to work, as
      delineated by the proxy of medical separation from military service. A
      multivariable logistic regression model was used to evaluate factors associated
      with an increased likelihood of medical separation following gunshot injury.
      RESULTS: Of the 1417 individuals meeting inclusion criteria, 40% (n = 572) of the
      cohort were medically separated in the time-period under study. Significant
      predictors of separation included non-thoracic injuries, increased injury
      severity score (ISS; OR 1.05; 95% CI 1.04, 1.06), Senior Enlisted (OR 3.90; 95%
      CI 2.16, 7.01), and Junior Enlisted military rank (OR 6.99; 95% CI 3.93, 12.44).
      CONCLUSIONS: This is the largest study in the literature to assess the long-term
      capacity to return to work following gunshot injury in any population.
      Individuals in high-demand occupations and those with non-thoracic wounds, or
      elevated ISS, should be counseled in the post-gunshot injury period regarding the
      negative associations of these characteristics with the capacity to return to
      work. Enhanced access to social services in the period following injury could
      similarly benefit individuals of low socioeconomic background.

PMID- 29191408
TI  - The retrieval of at least 25 lymph nodes should be essential for advanced gastric
      cancer patients with lymph node metastasis: A retrospective analysis of single
      institution database study design: Cohort study.
AB  - BACKGROUND: Recently, increased evidence have shown that the better prognosis of
      gastric cancer (GC) patients was associated with the larger number of retrieved
      lymph nodes (RLNs), but the optimal number of RLNs remains controversial. In the
      present study, we investigated whether adequate LN retrieval (>=15) was necessary
      to evaluate the prognosis of patients and attempted to propose an appropriate
      cutoff-point for the number of RLNs. METHODS: We reviewed 2246 GC patients who
      underwent radical gastrectomy in our research institution between January 1986
      and January 2008. All patients were divided into several groups based on the
      number of RLNs. The prognostic outcomes of different patient groups were compared
      and clinicopathologic features were analyzed. RESULTS: In the present study, our
      results indicated that >=15 RLNs showed a better survival outcome than inadequate
      LN retrieval (<15), regardless of the node-negative or node-positive GC patients
      (P < 0.001). For the more advanced GC patients (T2-T4 stage, N1-N3 stage, and
      stage II-stage III), the retrieval of 25-29 LNs could provide a better survival
      benefit compared with <25 or >=30 RLNs (P < 0.05). In addition, for the patients
      who underwent proximal or total gastrectomy, the superior prognosis was still
      observed in the patient group with 25-29 RLNs. CONCLUSION: The minimal goal of 15
      RLNs may not be enough to accurately evaluate prognosis of all patients and at
      least 25 RLNs should be necessary for advanced GC patients with lymph node
      metastasis.

PMID- 29191409
TI  - Reducing the sensation of electrical stimulation with dry electrodes by using an
      array of constant current sources.
AB  - Hydrogel electrodes are commonly used for functional and other electrical
      stimulation applications since the hydrogel layer has been shown to considerably
      reduce the perception of stimulation compared to dry electrodes. However, these
      hydrogel electrodes must be changed regularly as they dry out or become
      contaminated with skin cells and sweat products, thus losing their adhesiveness
      and resistive properties. Dry electrodes are longer lasting but are more
      uncomfortable due to unequal current distribution (current hogging). We
      hypothesise that if current through a dry electrode is equally shared amongst an
      array of small sub-electrodes, current hogging and thus the sensitivity perceived
      due to stimulation will be reduced. We constructed an 8 * 8 array of millimetre
      sized dry electrodes that could either be activated as individual current
      sources, or together as one large source. A study was performed with 13
      participants to investigate the differences in sensation between the two modes of
      operation. The results showed that 12 out of 13 participants found the new
      (distributed-constant-current) approach allowed higher stimulation for the same
      sensation. The differences in sensation between single and multiple sources
      became larger with higher intensity levels.

PMID- 29191410
TI  - Embodying Markov blankets: Comment on "Answering Schrodinger's question: A free
      energy formulation" by Maxwell James Desormeau Ramstead et al.

PMID- 29191411
TI  - A plea for "variational neuroethology": Comment on "Answering Schrodinger's
      question: A free-energy formulation" by M.J. Desormeau Ramstead et al.

PMID- 29191413
TI  - Correction to Lancet HIV 2017; 4: e546-46.

PMID- 29191412
TI  - Next year in The Lancet HIV.

PMID- 29191414
TI  - Comparative anatomy and angiography of the cardiac coronary venous system in four
      species: human, ovine, porcine, and canine.
AB  - INTRODUCTION: The coronary arterial system has been the subject of greater
      investigation than its venous system due to the importance of human coronary
      artery disease. With the advent of new percutaneous treatments, the anatomy of
      the coronary venous system has increasing relevancy. We compared the organization
      of the coronary venous circulation in three species commonly used in research and
      compared these to normal humans using both macroscopic anatomic and angiographic
      studies. ANIMALS: The anatomy of five explanted hearts from healthy dogs, pigs,
      and sheep were studied macroscopically, and 10 explanted hearts per animal
      species and 10 clinically normal human were examined by angiography. METHODS:
      Animal hearts were injected with latex and dissected macroscopically. The
      coronary venous system of humans was evaluated from clinical angiographic
      studies. In the animal hearts, a retrograde angiographic study was performed via
      a Foley catheter in the coronary sinus. RESULTS: The general organization of the
      coronary venous circulation was similar among humans, dogs, sheep, and pigs.
      Despite overall similarities to humans, animal hearts demonstrated the absence of
      the oblique vein of the left atrium and differences in position and organization
      of venous valves; venous diameters; number of tributary veins; and presence of an
      anastomosis between the left and right (human anterior and posterior) venous
      tree. The left azygos of the pig and sheep joined the coronary sinus.
      CONCLUSIONS: Anatomical differences must be considered when planning biomedical
      and veterinary studies incorporating cardiac veins. This study provides baseline
      data regarding structure and organization of the cardiac venous system.

PMID- 29191415
TI  - Paleoecology of the Serengeti during the Oldowan-Acheulean transition at Olduvai
      Gorge, Tanzania: The mammal and fish evidence.
AB  - Eight years of excavation work by the Olduvai Geochronology and Archaeology
      Project (OGAP) has produced a rich vertebrate fauna from several sites within Bed
      II, Olduvai Gorge, Tanzania. Study of these as well as recently re-organized
      collections from Mary Leakey's 1972 HWK EE excavations here provides a synthetic
      view of the faunal community of Olduvai during Middle Bed II at ~1.7-1.4 Ma, an
      interval that captures the local transition from Oldowan to Acheulean technology.
      We expand the faunal list for this interval, name a new bovid species, clarify
      the evolution of several mammalian lineages, and record new local first and last
      appearances. Compositions of the fish and large mammal assemblages support
      previous indications for the dominance of open and seasonal grassland habitats at
      the margins of an alkaline lake. Fish diversity is low and dominated by cichlids,
      which indicates strongly saline conditions. The taphonomy of the fish assemblages
      supports reconstructions of fluctuating lake levels with mass die-offs in
      evaporating pools. The mammals are dominated by grazing bovids and equids.
      Habitats remained consistently dry and open throughout the entire Bed II
      sequence, with no major turnover or paleoecological changes taking place. Rather,
      wooded and wet habitats had already given way to drier and more open habitats by
      the top of Bed I, at 1.85-1.80 Ma. This ecological change is close to the age of
      the Oldowan-Acheulean transition in Kenya and Ethiopia, but precedes the local
      transition in Middle Bed II. The Middle Bed II large mammal community is much
      richer in species and includes a much larger number of large-bodied species (>300
      kg) than the modern Serengeti. This reflects the severity of Pleistocene
      extinctions on African large mammals, with the loss of large species fitting a
      pattern typical of defaunation or 'downsizing' by human disturbance. However,
      trophic network (food web) analyses show that the Middle Bed II community was
      robust, and comparisons with the Serengeti community indicate that the
      fundamental structure of food webs remained intact despite Pleistocene
      extinctions. The presence of a generalized meat-eating hominin in the Middle Bed
      II community would have increased competition among carnivores and vulnerability
      among herbivores, but the high generality and interconnectedness of the Middle
      Bed II food web suggests this community was buffered against extinctions caused
      by trophic interactions.

PMID- 29191416
TI  - Metabolic syndrome in drug naive schizophrenic patients.
AB  - INTRODUCTION: Research in the last decade tried to focus on natural and unnatural
      causes of death in schizophrenic patients, but recent few years has focussed on
      emerging cardio-metabolic risk factors, as a cause of mortality in such patients.
      AIM OF THE STUDY: To assess the determinant of metabolic syndrome in drug naive
      schizophrenic patients. METHODOLOGY: It was a cross sectional study; 30 indoor
      patients with diagnosis of schizophrenia were included. Height, weight, waist
      circumference and Blood pressure assessment was done by using standard protocol.
      Fasting Blood Glucose (FBG), Triglyceride (TGs), High Density Lipoprotein (HDL)
      cholesterol, Low Density Lipoprotein (LDL) total cholesterol were measured.
      International Diabetes Federation (IDF) criteria was considered for establishing
      metabolic syndrome. Statistical analysis was done by using chi square and ANOVA.
      RESULTS: Majority of the patients were females; hailing from rural area;
      unskilled professional; educated up to below primary level; were single and Hindu
      by religion. Most common metabolic abnormality was low HDL in 76.6%; High TGs in
      26.6%; High SBP >=130mm Hg in 16.67%; DBP>85mm Hg in 13.33%; High FBS 10% of the
      patients. In risk assessment strongest risk factors for metabolic syndrome were
      high waist circumference, FBS and TGs. BMI, total cholesterol, LDL and VLDL were
      also observed as a risk factors in drug naive schizophrenic patients. CONCLUSION:
      HDL, FBS, TGs, waist circumference and BMI are all the strong risk factors for
      development of metabolic syndrome in drug naive schizophrenia patients.

PMID- 29191417
TI  - Effects of Classic Progressive Resistance Training Versus Eccentric-Enhanced
      Resistance Training in People With Multiple Sclerosis.
AB  - OBJECTIVE: To compare the effects of classic progressive resistance training
      (PRT) versus eccentric strength-enhanced training (EST) on the performance of
      functional tests and different strength manifestations in the lower limb of
      people with multiple sclerosis (PwMS). DESIGN: Experimental trial. SETTING:
      Strength training program. PARTICIPANTS: PwMS (N=52; 19 men, 33 women) belonging
      to MS associations from the Castilla y Leon, Spain. INTERVENTIONS: Participants
      were assigned to 1 of 2 groups: a control group that performed PRT or an
      experimental group that performed EST. In both groups, the knee extensor muscles
      were trained for 12 weeks. MAIN OUTCOME MEASURES: Before and after 12 weeks of
      training, maximal voluntary isometric contraction and 1 repetition maximum (1RM)
      of the knee extensors were evaluated, as were the Chair Stand Test (CST) and
      Timed 8-Foot Up and Go (TUG) functional tests. RESULTS: No differences were found
      between the groups in the initial values for different tests. Intragroup
      comparisons found significant differences in CST (F=69.4; P<.001), TUG (F=40.0;
      P<.001), and 1RM (F=57.8; P<.001). For intergroup comparisons, EST presented
      better results than PRT in the CST (EST, 4.7%+/-2.8%; PRT, 1.9%+/-2.8%; F=13.1;
      P=.001) and TUG (EST, -2.9+/-4.7; PRT, -.41+/-5.6; F=5.6; P=.022). CONCLUSIONS:
      In PwMS, EST leads to improvements in 1RM, TUG, and CST that are similar to those
      of PRT. However, for patients who participated in this study, the EST seems to
      promote a better transfer of strength adaptations to the functional tests, which
      are closer to daily-living activities.

PMID- 29191419
TI  - Application of guar gum in brine clarification and oily water treatment.
AB  - The increasing amount of oil wastewater is causing serious damage to the
      environment. Oily water is a worrisome by-product of the oil industry due to its
      growing volume in mature basins and complex chemical composition. Low-cost
      polymers are being used as alternative materials to treat oily waters after
      treatment by conventional methods, oil and grease (O&G) concentration being the
      primary parameter for final disposal. In this respect, guar gum can be used to
      treat petroleum-contaminated waters, with the advantage of being a low-cost,
      highly-hydrophilic natural polymer. In this study, guar gum, under specific
      conditions, shapes itself into three-dimensional structures with interesting
      physicochemical properties. The salting out effect occurs with reticulation of
      the polymeric chains by borate ions and in the presence of electrolytes, reducing
      the solubility of the polymeric network in the solution and leading to an
      electrolyte- and polymer-rich phase. When the guar gum gel was prepared in situ
      in the produced water, after the salting out effect, the oil was imprisoned in
      the interstices of the collapsed gel. The gelling guar gum was highly efficient
      in synthetic oily waters. In the case of initial O&G above 100ppm, the oil
      removal percentage was above 90%.

PMID- 29191418
TI  - Anti-allergic effects of novel sulfated polysaccharide sacran on mouse model of
      2,4-Dinitro-1-fluorobenzene-induced atopic dermatitis.
AB  - In this study, in order to investigate the potential of the novel polysaccharide
      sacran from Aphanothece Sacrum for development of atopic dermatitis (AD), we
      evaluated the potential of pretreatment with topical sacran to prevent the
      development of hapten (dinitrofluorobenzene: DNFB)-induced AD-like disease in
      mice. In the AD model mice, sacran markedly ameliorated AD symptoms such as
      scratching behavior and edema in ear. In addition, sacran significantly increased
      water content of the stratum corneum which regulates the skin barrier function.
      Furthermore, sacran significantly inhibited inflammatory cytokine and chemokine
      mRNA levels in the dermatitis skin as well as the IgE antibody level in serum.
      Sacran inhibited inflammatory cytokines mRNA production from Jurkat cells derived
      from human leukemia T cells after stimulation with phorbol 12-myristate 13
      acetate/ionomycin. Meanwhile, sacran did not inhibit the proliferation of primary
      B cells stimulated with lipopolysaccharide. These results suggest that sacran has
      good anti-allergic effect on AD model mice, probably due to the amelioration of
      skin barrier function and suppression of immune responses.

PMID- 29191420
TI  - Effect of duration of sonication during gelatinization on properties of tapioca
      starch water hyacinth fiber biocomposite.
AB  - This paper characterizes properties of biocomposite sonicated during
      gelatinization. The biocomposite consisted of tapioca starch based plastic
      reinforced by 10% volume fraction of water hyacinth fiber (WHF). During
      gelatinization, the biocomposite was poured into a rectangular glass mold then
      vibrated in an ultrasonic bath using 40kHz, 250W for varying durations (0, 15,
      30, and 60min). The resulting biocomposite was then dried in a drying oven at 50
      degrees C for 20h. The results of this study indicate that a biocomposite with
      optimal properties can be produced using tapioca starch and WHF if the
      gelatinizing mixture is exposed to ultrasound vibration for 30min. After this
      vibration duration, tensile strength (TS) and tensile modulus (TM) increased 83%
      and 108%. A further 60min vibration only increased the TS at 13% and TM at 23%.
      Moisture resistance of the biocomposite after vibration increased by around 25%
      reaching a maximal level after 30min. Thermal resistance of the vibrated
      biocomposites was also increased.

PMID- 29191421
TI  - Comparative studies of the low-resolution structure of two p23 co-chaperones for
      Hsp90 identified in Plasmodium falciparum genome.
AB  - The p23 proteins are small acidic proteins that aid the functional cycle of the
      Hsp90 molecular chaperone. Such co-chaperone acts by temporarily inhibiting the
      ATPase activity of Hsp90 and exhibits intrinsic chaperone activity, suggesting
      independent roles. A search for p23 in the Plasmodium falciparum genome led to
      the identification of two putative proteins showing 13% identity to each other
      and approximately 20% identity to human p23. To understand the presence of two
      p23 proteins in this organism, we generated recombinant p23 proteins (Pfp23A and
      Pfp23B) and investigated their structure and function. The proteins presented
      some similarities and dissimilarities in structural contents and showed different
      chemical and thermal stabilities, with Pfp23A being more stable than Pfp23B,
      suggesting that these proteins may present different functions in this organism.
      Both Pfp23 proteins behaved as elongated monomers in solution and were capable of
      preventing the thermal-induced aggregation of model client proteins with
      different efficiencies. Finally, the Pfp23 proteins inhibited the ATPase activity
      of recombinant P. falciparum Hsp90 (PfHsp90). These results validate the studied
      proteins as p23 proteins and co-chaperones of PfHsp90.

PMID- 29191422
TI  - Resistant starch produces antidiabetic effects by enhancing glucose metabolism
      and ameliorating pancreatic dysfunction in type 2 diabetic rats.
AB  - The aim of the study was to evaluate the hypoglycemic effect of low, medium, and
      high doses of resistant starch type 2(RS2;100, 150, and 200g/kg) for 28days and
      explore its potential mechanism of this effect in type 2 diabetic rats treated
      with high-glucose-fat diet and low-dose streptozotocin(STZ). RS2 treatment
      induced better regulation of lipid in plasma and liver, fructosamine, oral
      glucose tolerance test, insulin, glucose metabolism and pancreatic damage in
      diabetic rats. The best hypoglycemic activity was observed after the medium-dose
      RS2 treatment. Western blot and real-time Polymerase Chain Reaction (RT
      PCR)results revealed that phosphoenolpyruvate carboxykinase and glucose-6
      phosphatase are involved in glyconeogenesis in the liver, and pancreatic duodenum
      homeobox 1 controls gluconeogenesis balance by regulating the expression levels
      of glucose kinase and glucose transport protein 2 in the liver and pancreas.
      Furthermore, the expression levels of insulin receptor substrate 1 and insulin
      receptor substrate 2 were enhanced in the pancreas. Results suggested that
      decreases in the blood glucose levels of diabetic rats fed with RS are regulated
      through the alteration of the expression levels of the genes related to glucose
      metabolism and amelioration of pancreatic dysfunction.

PMID- 29191423
TI  - An electrochemical nitric oxide biosensor based on immobilized cytochrome c on a
      chitosan-gold nanocomposite modified gold electrode.
AB  - Goldnanoparticle (AuNPs), chitosan (CS), cytochrome c (Cyt c) and Nafion were
      immobilized on the surface of a gold electrode to form a Nafion/Cyt c/CS-3
      Mercaptopropionic acid (MPA)-AuNPs/cysteamine-MPA (SAMs)-Au electrode. The CS-MPA
      AuNPs nanocomposite was characterized by UV-vis spectroscopy. Electrochemical
      behavior of modified electrode was analyzed by electrochemical impedance
      spectroscopy (EIS), cyclic voltammetry (CV) and chronoamperometry. Uv-vis results
      showed that CS-MPA-AuNPs nanocomposite could improve electron transfer between
      Cyt c and electrode surface and keep the catalytic activity of Cyt c. A pair of
      well defined and reversible redox peaks could be observed for the modified
      electrode in a 0.1M phosphate buffer solution (PBS, pH 7.0). The anodic and
      cathodic peak potentials of Cyt c/CS-MPA-AuNPs/SAMs-Au electrode were at 0.006V
      and -0.043V (vs. Ag/AgCl), respectively. Particular electrocatalytic activity was
      shown by Cyt c on CS-MPA-AuNPs layer for nitric oxide (NO) reduction. The
      relationship between peak current and NO concentration was linear in the range of
      1*10-7-21.5*10-7M with a detection limit of 0.45*10-7M (S/N=3).The sensitivity
      was 0.199MUA/MUM. The obtained results indicating that the newly developed
      biosensor was quite selective and stable which was used for accurate and exact
      detection of NO.

PMID- 29191424
TI  - Receptor-mediated targeted delivery of DNA using Lactoferrin nanoparticles.
AB  - Efficient gene delivery facilitated by non-viral vectors, is comparatively safer
      alternative than viral carriers. Current approaches to gene delivery largely
      depends on methods that overcome cellular and tissue barriers impeding efficient
      DNA delivery. While the conventional delivery systems have the drawback of low
      cellular uptake and off target effects, the receptor-mediated gene delivery
      system has shown remarkable breakthrough. In that context exploiting the specific
      receptor targeting properties of lactoferrin protein, we have developed pDNA
      loaded lactoferrin protein nanoparticles (pDNA-LfNPs). pDNA-LfNPs were spherical
      in shape within the size range of 140+/-20nm. They were found to be resistant
      against nuclease digestion and stable under long storage. Additionally, LfNPs
      were biocompatible and have targeting ability to facilitate gene uptake by
      receptor mediated internalization in lactoferrin receptor expressing cell lines.
      It is also evident from our studies that Lf nanoparticles did not exhibit any
      cytotoxicity even at the highest concentration. Here we first time report the use
      of lactoferrin nanoparticles as a gene delivery carrier with targeting abilities.

PMID- 29191426
TI  - [Customized external nasal splint after rhinoplasty, introduction to the "tissu
      modelage"].
AB  - The authors report their experience of 2 years (43 patients) using a customized
      splint consists of thermoplastic which is molded on the new nose after
      rhinoplasty, according to a process comparable to that used by dentists to make
      the gutters. This splint will be applied several weeks to guide healing in a
      desired direction. The molding of the nose can be re-sculpted to guide the
      scarring to a better result. Lightweight, washable, discreet, our splint works to
      the advantage to be worn without discomfort for several weeks in order to improve
      the efficiency of contention.

PMID- 29191425
TI  - GH11 xylanase from Aspergillus tamarii Kita: Purification by one-step
      chromatography and xylooligosaccharides hydrolysis monitored in real-time by mass
      spectrometry.
AB  - The present study describes the one-step purification and biochemical
      characterization of an endo-1,4-beta-xylanase from Aspergillus tamarii Kita.
      Extracellular xylanase was purified to homogeneity 7.43-fold through CM
      cellulose. Enzyme molecular weight and pI were estimated to be 19.5kDa and 8.5,
      respectively. The highest activity of the xylanase was obtained at 60 degrees C
      and it was active over a broad pH range (4.0-9.0), with maximal activity at pH
      5.5. The enzyme was thermostable at 50 degrees C, retaining more than 70% of its
      initial activity for 480min. The K0.5 and Vmax values on beechwood xylan were
      8.13mg/mL and 1,330.20MUmol/min/mg of protein, respectively. The ions Ba2+ and
      Ni2+, and the compounds beta-mercaptoethanol and DTT enhanced xylanase activity,
      while the heavy metals (Co2+, Cu2+, Hg+, Pb2+ and Zn2+) strongly inhibited the
      enzyme, at 5mM. Enzymatic hydrolysis of xylooligosaccharides monitored in real
      time by mass spectrometer showed that the shortest xylooligosaccharide more
      efficiently hydrolyzed by A. tamarii Kita xylanase corresponded to xylopentaose.
      In agreement, HPLC analyzes did not detect xylopentaose among the hydrolysis
      products of xylan. Therefore, this novel GH11 endo-xylanase displays a series of
      physicochemical properties favorable to its application in the food, feed,
      pharmaceutical and paper industries.

PMID- 29191427
TI  - Antivirals acting on viral envelopes via biophysical mechanisms of action.
AB  - Most antivirals target viral proteins and are specific for only one virus, or
      viral type. Whereas viral proteins are encoded in the plastic viral genome,
      virion lipids are not and their rearrangements during fusion are conserved among
      otherwise unrelated enveloped viruses. Antivirals that inhibit these lipid
      rearrangements could thus pose a high barrier to resistance and have broad
      spectrum activity. Fusion occurs through a hemifusion stalk in which only the
      outer leaflets are fused and thus curved with a smaller radius for the polar
      heads than for the hydrophobic tails (negative curvature). Outer leaflets
      enriched in phospholipids with head groups of larger cross sections than their
      lipid tails ("inverted cone") disfavor negative curvature, inhibiting fusion. The
      rigid amphipathic fusion inhibitors (RAFIs) are synthetic compounds of inverted
      cone molecular geometry. They inhibit infectivity of otherwise unrelated
      enveloped viruses. The leading RAFI, aUY11, has an ethynyl-perylene hydrophobic
      and an uracil-arabinose polar moiety. aUY11 intercalates in viral envelopes and
      inhibits virion-to-cell fusion of a broad spectrum of otherwise unrelated
      enveloped viruses. Previous studies showed that amphipathicity, rigidity, and
      inverted cone molecular geometry were required. We propose that the inverted cone
      molecular geometry of the RAFIs increases the energy barrier for the hemifusion
      stalk, inhibiting fusion. Then, chemically distinct compounds with similar
      amphipathicity, rigidity, and inverted cone shape would have similar antiviral
      potencies, regardless of specific chemical groups. Alternatively, the perylene
      group exposed to visible light may induce viral lipid peroxidation. Then, the
      perylene group and absorbance at visible spectrum would be required. We now
      evaluated twenty-five chemically distinct RAFIs. The perylene moiety and
      absorption at visible spectrum were not required, but a minimum length of the
      hydrophobic moiety was, 10.3 A. The arabino moiety could be modified or replaced
      by other groups. Cytidine was not tolerated. Bilayer intercalation was required
      but not sufficient. The vast majority of RAFIs had no overt cytotoxicity (CC50 >
      20 MUM; TI > 250-1200). Carbonyl or butylamide substitutions for arabino, or
      cytidine replacement for uracil, increased cytotoxicity. Cytotoxicity was mainly
      determined by the polar moiety and there was no correlation between antiviral and
      cytostatic activities. The definition of the effects of shape and chemical groups
      of the RAFIs opens the possibility to the rational design of lipid-acting
      antivirals active against a broad spectrum of enveloped viruses.

PMID- 29191428
TI  - Monoamine and neuroendocrine gene-sets associate with frustration-based
      aggression in a gender-specific manner.
AB  - Investigating phenotypic heterogeneity in aggression and understanding the
      molecular biological basis of aggression subtypes may lead to new prevention and
      treatment options. In the current study, we evaluated the taxonomy of aggression
      and examined specific genetic mechanisms underlying aggression subtypes in
      healthy males and females. Confirmatory Factor Analysis (CFA) was used to
      replicate a recently reported three-factor model of the Reactive Proactive
      Questionnaire (RPQ) in healthy adults (n=661; median age 24.0 years; 41% male).
      Gene-set association analysis, aggregating common genetic variants within (a
      combination of) three molecular pathways previously implicated in aggression,
      i.e. serotonergic, dopaminergic, and neuroendocrine signaling, was conducted with
      MAGMA software in males and females separately (total n=395) for aggression
      subtypes. We replicate the three-factor CFA model of the RPQ, and found males to
      score significantly higher on one of these factors compared to females: proactive
      aggression. The genetic association analysis showed a female-specific association
      of genetic variation in the combined gene-set with a different factor of the RPQ;
      reactive aggression due to internal frustration. Both the neuroendocrine and
      serotonergic gene-sets contributed significantly to this association. Our genetic
      findings are subtype- and sex-specific, stressing the value of efforts to reduce
      heterogeneity in research of aggression etiology. Importantly, subtype- and sex
      differences in the underlying pathophysiology of aggression suggest that optimal
      treatment options will have to be tailored to the individual patient. Male and
      female needs of intervention might differ, stressing the need for sex-specific
      further research of aggression. Our work highlights opportunities for sample size
      maximization offered by population-based studies of aggression.

PMID- 29191429
TI  - Successful Repatriation of Breast Cancer Surveillance for High-Risk Women to the
      UK National Health Service Breast Screening Programme.
AB  - BACKGROUND: Since April 2013, the UK's National Health Service Breast Screening
      Programme (NHSBSP) centers have been obliged to provide services for women at the
      highest risk of breast cancer, including those carrying highly penetrant single
      gene mutations (BRCA1, BRCA2, TP53). Since then, such individuals previously
      undergoing surveillance in the Royal Marsden Hospital were referred to their
      local NHSBSP centers. We aimed to assess patient experience of surveillance
      provided by local NHSBSP services at 1 and 3 years after repatriation. PATIENTS
      AND METHODS: High-risk gene mutation carriers referred to the NHSBSP for breast
      cancer surveillance were identified from a departmental database in the Cancer
      Genetics Unit and invited to complete questionnaires about their experience of
      surveillance under this new pathway, first in 2014 and again in 2016. RESULTS:
      Three hundred forty-six individuals were invited to participate in 2014, of whom
      182 responded (53%). A total of 464 patients were invited in 2016, of whom 246
      (53%) completed the second questionnaire. Ninety-four percent of patients with
      residual breast tissue received some screening at the first (n = 161) and second
      (n = 185) time points. Ninety-one percent of patients (n = 146) received at least
      recommended surveillance in the year preceding the initial survey, a proportion
      decreasing slightly by the second time point (n = 164, 87%). Seventeen percent of
      individuals required additional diagnostic investigations, with cancers detected
      in 2%. These proportions remained stable between surveys. CONCLUSION:
      Repatriation of high-risk individuals from Royal Marsden Hospital to NHSBSP
      centers has been successfully accomplished. Most individuals received appropriate
      recommended annual surveillance. Further improvements are required to ensure
      equal and timely provision of recommended surveillance.

PMID- 29191430
TI  - Oculomotor abnormalities in children with Niemann-Pick type C.
AB  - Niemann-Pick type C (NP-C) is a rare recessive disorder associated with
      progressive supranuclear gaze palsy. Degeneration occurs initially for vertical
      saccades and later for horizontal saccades. There are studies of oculomotor
      degeneration in adult NP-C patients [1, 2] but no comparable studies in children.
      We used high-resolution video-based eye tracking to record monocular vertical and
      horizontal eye movements in 2 neurological NP-C patients (children with
      clinically observable oculomotor abnormalities) and 3 pre-neurological NP-C
      patients (children without clinically observable oculomotor abnormalities).
      Saccade onset latency, saccade peak velocity and saccade curvature were compared
      to healthy controls (N=77). NP-C patients had selective impairments of vertical
      saccade peak velocity and vertical saccade curvature, with slower peak velocities
      and greater curvature. Changes were more pronounced in neurological than pre
      neurological patients, showing that these measures are sensitive to disease
      progress, but abnormal curvature and slowed downward saccades were present in
      both groups, showing that eye-tracking can register disease-related changes
      before these are evident in a clinical exam. Both slowing, curvature and the
      detailed characteristics of the curvature we observed are predicted by the
      detailed characteristics of RIMLF population codes. Onset latencies were not
      different from healthy controls. High-resolution video-based eye tracking is a
      promising sensitive and objective method to measure NP-C disease severity and
      neurological onset. It may also help evaluate responses to therapeutic
      interventions.

PMID- 29191431
TI  - Epidemiological characteristics of lower extremity arterial disease in Chinese
      diabetes patients at high risk: a prospective, multicenter, cross-sectional
      study.
AB  - AIMS: To determine the epidemiological characteristics of lower extremity
      arterial disease (LEAD) in high-risk patients and identify practical gaps in LEAD
      management. METHODS: This cross-sectional study consecutively enrolled 10681
      patients with type 2 diabetes from 30 hospitals across China from June 2016 to
      January 2017. All patients were assessed for LEAD by the Ankle-Brachial Index in
      conjunction with lower limb ultrasonography according to local guidelines.
      RESULTS: The mean age of patients was 64.2 years, and the median duration of
      diabetes was 9.0 years. The overall prevalence of LEAD was 21.2%, with 10.6% of
      patients diagnosed with LEAD before enrollment and 11.8% newly diagnosed at the
      present visit. Patients with older age, hypertension and dyslipidemia as well as
      those who smoked were at higher risk of developing LEAD. Only 55.0%, 28.2%, and
      42.5% of participating patients reached the guideline-recommended goals for
      glycemic, blood pressure, and lipid control, respectively. Anti-hypertensive
      agents, lipid lowering therapies, anti-platelet agents, and vasodilators were
      underused, especially in newly diagnosed LEAD patients (44.1%, 46.2%, 35.3%, and
      31.7%, respectively). CONCLUSIONS: Despite the high prevalence of LEAD, it was
      still found to be underdiagnosed and undertreated in Chinese diabetes patients.
      More efforts should be directed at encouraging awareness of early LEAD and
      achieving guideline-recommended goals in type 2 diabetes patients.

PMID- 29191432
TI  - Cereal fiber, fruit fiber, and type 2 diabetes: Explaining the paradox.
AB  - While the relationship between dietary fiber and type 2 diabetes mellitus (T2DM)
      has been much studied, the evidence about its role in the prevention and control
      of this condition has been conflicting. We critically evaluate prospective cohort
      studies and randomized controlled trials (RCTs) that examined
      insoluble/nonviscous/cereal fiber and soluble/viscous/fruit fiber in relation to
      risk of T2DM. Taken as a whole this evidence indicates that, in the quantities
      typically eaten, cereal fiber is protective against T2DM while fruit fiber gives
      little protection. We argue that the protective action of cereal fiber may be
      explained by the modulating effects of gut microbiota through mechanisms such as:
      1) improving glucose tolerance via energy metabolism pathways (colonic
      fermentation and generation of short-chain fatty acids); 2) reducing
      inflammation; and 3) altering the immune response. By gaining more knowledge of
      specific host and gut microbial functional pathways involved in T2DM development
      and the potential role of cereal fiber, appropriate disease prevention and
      intervention strategies may be developed.

PMID- 29191433
TI  - How does globalisation affect women's health?

PMID- 29191435
TI  - There is no weekend effect in hip fracture surgery - A comprehensive analysis of
      outcomes.
AB  - BACKGROUND: Previous studies have shown that some patient groups suffer adverse
      outcomes if they are acutely admitted to hospital over a weekend. We aimed to
      investigate this 'weekend effect' at our centre in patients presenting with a hip
      fracture. METHODS: Consecutive patients undergoing acute hip fracture surgery
      were identified from a prospective database. Patient demographics, co
      morbidities, fracture type, admission blood parameters were examined. Outcomes
      analysed included 30-day, 90-day and 1-year mortality as well as length of stay,
      re-operations and delay to surgery. The data were analysed with regards to day of
      admission and day of surgery separately. RESULTS: A total of 1326 patients were
      included, of which 368 patients were admitted over a weekend and 411 patients had
      their operation over a weekend. Overall 30-day mortality was 7.6% (101 patients),
      whilst the 90-day and 1-year mortalities were 15.3% and 26.8% (203 and 356
      patients). There were no significant differences in any of the outcomes based on
      the day of admission or the day of surgery. Multivariate analysis for 30-day
      mortality demonstrated the following variables to be significant predictors:
      admission urea levels (hazard ratio (HR) 1.042, p = 0.027), age (HR 1.058, p <
      0.001), admission source (HR 1.428, p < 0.001), surgical delay >48 h (HR 1.853, p
      = 0.004), male gender (HR 1.967, p = 0.003), previous stroke (HR 2.261, p =
      0.038), acute chest infection (4.240, p < 0.001) and chronic liver disease (HR
      4.581, p = 0.014). CONCLUSION: This data suggests that there is no significant
      weekend effect in hip fracture surgery and mortality is affected by patient co
      morbidities and delay to surgery.

PMID- 29191434
TI  - The gendered effects of foreign investment and prolonged state ownership on
      mortality in Hungary: an indirect demographic, retrospective cohort study.
AB  - BACKGROUND: Research on the health outcomes of globalisation and economic
      transition has yielded conflicting results, partly due to methodological and data
      limitations. Specifically, the outcomes of changes in foreign investment and
      state ownership need to be examined using multilevel data, linking macro-effects
      and micro-effects. We exploited the natural experiment offered by the Hungarian
      economic transition by means of a multilevel study designed to address these gaps
      in the scientific literature. METHODS: For this indirect demographic,
      retrospective cohort study, we collected multilevel data related to Hungary
      between 1995 and 2004 from the PrivMort database and other sources at the town,
      company, and individual level to assess the relation between the dominant company
      ownership of a town and mortality. We grouped towns into three ownership
      categories: dominant state, domestic private, and foreign ownership. We did
      population surveys in these towns to collect data on vital status and other
      characteristics of survey respondents' relatives. We assessed the relation
      between dominant ownership and mortality at the individual level. We used
      discrete-time survival modelling, adjusting for town-level and individual-level
      confounders, with clustered SEs. FINDINGS: Of 83 eligible towns identified, we
      randomly selected 52 for inclusion in the analysis and analysed ownership data
      from 262 companies within these towns. Additionally, between June 16, 2014, and
      Dec 22, 2014, we collected data on 78 622 individuals from the 52 towns, of whom
      27 694 were considered eligible. After multivariable adjustment, we found that
      women living in towns with prolonged state ownership had significantly lower odds
      of dying than women living in towns dominated by domestic private ownership (odds
      ratio [OR] 0.74, 95% CI 0.61-0.90) or by foreign investment (OR 0.80, 0.69-0.92).
      INTERPRETATION: Prolonged state ownership was associated with protection of life
      chances during the post-socialist transformation for women. The indirect economic
      benefits of foreign investment do not translate automatically into better health
      without appropriate industrial and social policies. FUNDING: The European
      Research Council.

PMID- 29191436
TI  - Systematic profiling of alternative splicing signature reveals prognostic
      predictor for ovarian cancer.
AB  - OBJECTIVE: The majority of genes are alternatively spliced and growing evidence
      suggests that alternative splicing is modified in cancer and is associated with
      cancer progression. Systematic analysis of alternative splicing signature in
      ovarian cancer is lacking and greatly needed. METHODS: We profiled genome-wide
      alternative splicing events in 408 ovarian serous cystadenocarcinoma (OV)
      patients in TCGA. Seven types of alternative splicing events were curated and
      prognostic analyses were performed with predictive models and splicing network
      built for OV patients. RESULTS: Among 48,049 mRNA splicing events in 10,582
      genes, we detected 2,611 alternative splicing events in 2,036 genes which were
      significant associated with overall survival of OV patients. Exon skip events
      were the most powerful prognostic factors among the seven types. The area under
      the curve of the receiver-operator characteristic curve for prognostic predictor,
      which was built with top significant alternative splicing events, was 0.937 at
      2,000 days of overall survival, indicating powerful efficiency in distinguishing
      patient outcome. Interestingly, splicing correlation network suggested obvious
      trends in the role of splicing factors in OV. CONCLUSIONS: In summary, we built
      powerful prognostic predictors for OV patients and uncovered interesting splicing
      networks which could be underlying mechanisms.

PMID- 29191437
TI  - Urinary diversion in the genitourinary cancer survivor.
AB  - Urinary diversion has been in the scope of practice of Gynecologic Oncologists
      since the inception of the sub-specialty. However, many fewer urinary diversions
      are performed currently than in the past due to improved prevention of cervical
      cancer. The intent of this article is to provide a state of the art review for
      Gynecologic Oncologists. Surgeons performing these complex procedures must be
      knowledgeable about the differences between various types of continent and non
      continent urinary diversions, and the principles of pre and post-operative care.
      This includes the indications for surgery and pre-operative considerations, types
      of urinary diversion including continent and non-continent diversions, and the
      need for long-term follow-up with patients who undergo urinary diversion
      requiring lifelong follow up and testing for surveillance of the upper urinary
      tracts and to monitor for nutritional and metabolic alterations.

PMID- 29191438
TI  - Real-time EEG-defined excitability states determine efficacy of TMS-induced
      plasticity in human motor cortex.
AB  - BACKGROUND: Rapidly changing excitability states in an oscillating neuronal
      network can explain response variability to external stimulation, but if
      repetitive stimulation of always the same high- or low-excitability state results
      in long-term plasticity of opposite direction has never been explored in vivo.
      OBJECTIVE/HYPOTHESIS: Different phases of the endogenous sensorimotor MU-rhythm
      represent different states of corticospinal excitability, and repetitive
      transcranial magnetic stimulation (rTMS) of always the same high- vs. low
      excitability state results in long-term plasticity of different direction.
      METHODS: State-dependent electroencephalography-triggered transcranial magnetic
      stimulation (EEG-TMS) was applied to target the EEG negative vs. positive peak of
      the sensorimotor MU-rhythm in healthy subjects using a millisecond resolution
      real-time digital signal processing system. Corticospinal excitability was
      indexed by motor evoked potential amplitude in a hand muscle. RESULTS: EEG
      negative vs. positive peak of the endogenous sensorimotor MU-rhythm represent
      high- vs. low-excitability states of corticospinal neurons. More importantly,
      otherwise identical rTMS (200 triple-pulses at 100 Hz burst frequency and ~1 Hz
      repetition rate), triggered consistently at this high-excitability vs. low
      excitability state, leads to long-term potentiation (LTP)-like vs. no change in
      corticospinal excitability. CONCLUSIONS: Findings raise the intriguing
      possibility that real-time information of instantaneous brain state can be
      utilized to control efficacy of plasticity induction in humans.

PMID- 29191439
TI  - Effects of cerebellar neuromodulation in movement disorders: A systematic review.
AB  - BACKGROUND: The cerebellum is involved in the pathophysiology of many movement
      disorders and its importance in the field of neuromodulation is growing.
      OBJECTIVES: To review the current evidence for cerebellar modulation in movement
      disorders and its safety profile. METHODS: Eligible studies were identified after
      a systematic literature review of the effects of cerebellar modulation in
      cerebellar ataxia, Parkinson's disease (PD), essential tremor (ET), dystonia and
      progressive supranuclear palsy (PSP). Neuromodulation techniques included
      transcranial magnetic stimulation (TMS), transcranial direct current stimulation
      (tDCS) and deep brain stimulation (DBS). The changes in motor scores and the
      incidence of adverse events after the stimulation were reviewed. RESULTS: Thirty
      four studies were included in the systematic review, comprising 431 patients. The
      evaluation after stimulation ranged from immediately after to 12 months after.
      Neuromodulation techniques improved cerebellar ataxia due to vascular or
      degenerative etiologies (TMS, tDCS and DBS), dyskinesias in PD patients (TMS),
      gross upper limb movement in PD patients (tDCS), tremor in ET (TMS and tDCS),
      cervical dystonia (TMS and tDCS) and dysarthria in PSP patients (TMS). All the
      neuromodulation techniques were safe, since only three studies reported the
      existence of side effects (slight headache after TMS, local skin erythema after
      tDCS and infectious complication after DBS). Eleven studies did not mention if
      adverse events occurred. CONCLUSIONS: Cerebellar modulation can improve specific
      symptoms in some movement disorders and is a safe and well-tolerated procedure.
      Further studies are needed to lay the groundwork for new researches in this
      promising target.

PMID- 29191441
TI  - Inadequate HIV care after incarceration: case closed.

PMID- 29191440
TI  - Predictors of linkage to HIV care and viral suppression after release from jails
      and prisons: a retrospective cohort study.
AB  - BACKGROUND: Incarceration provides an opportunity for engagement in HIV care but
      is associated with poor HIV treatment outcomes after release. We aimed to assess
      post-release linkage to HIV care (LTC) and the effect of transitional case
      management services. METHODS: To create a retrospective cohort of all adults with
      HIV released from jails and prisons in Connecticut, USA (2007-14), we linked
      administrative custody and pharmacy databases with mandatory HIV/AIDS
      surveillance monitoring and case management data. We examined time to LTC
      (defined as first viral load measurement after release) and viral suppression at
      LTC. We used generalised estimating equations to show predictors of LTC within 14
      days and 30 days of release. FINDINGS: Among 3302 incarceration periods for 1350
      individuals between 2007 and 2014, 672 (21%) of 3181 periods had LTC within 14
      days of release, 1042 (34%) of 3064 had LTC within 30 days of release, and 301
      (29%) of 1042 had detectable viral loads at LTC. Factors positively associated
      with LTC within 14 days of release are intermediate (31-364 days) incarceration
      duration (adjusted odds ratio 1.52; 95% CI 1.19-1.95), and transitional case
      management (1.65; 1.36-1.99), receipt of antiretroviral therapy during
      incarceration (1.39; 1.11-1.74), and two or more medical comorbidities (1.86;
      1.48-2.36). Reincarceration (0.70; 0.56-0.88) and conditional release (0.62; 0.50
      0.78) were negatively associated with LTC within 14 days. Hispanic ethnicity,
      bonded release, and psychiatric comorbidity were also associated with LTC within
      30 days but reincarceration was not. INTERPRETATION: LTC after release is
      suboptimal but improves when inmates' medical, psychiatric, and case management
      needs are identified and addressed before release. People who are rapidly cycling
      through jail facilities are particularly vulnerable to missed linkage
      opportunities. The use of integrated programmes to align justice and health-care
      goals has great potential to improve long-term HIV treatment outcomes. FUNDING:
      US National Institutes of Health.

PMID- 29191442
TI  - Adding Patella Resurfacing After Circumpatellar Electrocautery Did Not Improve
      the Clinical Outcome in Bilateral Total Knee Arthroplasty in Chinese Population:
      A Prospective Randomized Study.
AB  - BACKGROUND: In total knee arthroplasty (TKA), handling of the patella surface is
      still quite controversial. We carried out a prospective randomized study to
      compare circumpatellar electrocautery plus patella resurfacing vs circumpatellar
      electrocautery only in the single-staged bilateral TKA in Chinese population.
      METHODS: One hundred five patients diagnosed with late-staged osteoarthritis who
      received single-staged bilateral TKA were screened and 53 patients were included.
      All patients received the same posterior cruciate-stabilizing total knee
      prostheses. Patients were randomized to receive circumpatellar electrocautery
      plus patellar resurfacing or circumpatellar electrocautery only for the first
      TKA, and the second knee received the opposite treatment. All patients were
      followed for a minimum of 2 years. RESULTS: No differences were found with regard
      to Knee Society Score, Feller score, anterior knee pain, and revision rates.
      Fifty-two percent of patients had no preference with regard to pain and function,
      27% of patients preferred the resurfacing plus circumpatellar electrocautery knee
      while 21% of the patients preferred the circumpatellar electrocautery only knee.
      The Insall-Salvati index and the patella tilt were a little smaller in the
      resurfacing group. One patient (2.1%) in the circumpatellar electrocautery group
      underwent a patella resurfacing revision for severe anterior knee pain and
      patella subluxation. CONCLUSION: Equivalent clinical results for circumpatellar
      electrocautery plus resurfacing and circumpatellar electrocautery alone of the
      patella in TKA were demonstrated in selective Chinese population with thick
      enough patella.

PMID- 29191443
TI  - A Meta-Analysis of Patellar Replacement in Total Knee Arthroplasty for Patients
      With Knee Osteoarthritis.
AB  - BACKGROUND: This meta-analysis (MA) aims at comparing the clinical outcomes of
      resurfacing and nonresurfacing the patella in patients undergoing total knee
      arthroplasty in the treatment of knee osteoarthritis. METHODS: Randomized
      controlled trials were included by retrieving data from electronic English
      databases. Both fixed and random-effects models were employed, and standardized
      mean difference and 95% confidence intervals were calculated. Stata13.1 software
      was used for statistical analysis for all the studies included to compare the
      differences in improving Knee Society Clinical Score and Knee Society Function
      Score as well as the reduction in rates of infection, reoperation, and anterior
      knee pain. RESULTS: A total of 394 studies were initially included in this MA.
      About 20 randomized controlled trials which met the inclusion criteria were
      finally enrolled in this MA. The results of our MA showed that the reoperation
      rate of the patellar resurfacing group was lower than that of the nonresurfacing
      group. The subgroup analysis was performed according to the follow-up time and
      revealed that the increase in the Knee Society Clinical Score was higher in the
      patellar resurfacing group than that in the nonresurfacing group in the follow-up
      period of 1 to 2 years. The risk of reoperation rate was lower in the patellar
      resurfacing group than that in the nonresurfacing group, while there were no
      statistical differences in the follow-up time over 2 years. CONCLUSION: Our study
      suggests that during the follow-up of 1 to 2 years, patellar resurfacing can
      significantly increase the Knee Society Clinical Score and reduce the reoperative
      rates in patients with knee osteoarthritis.

PMID- 29191444
TI  - Implant Survival and Complication Profiles of Endoprostheses for Treating Tumor
      Around the Knee in Adults: A Systematic Review of the Literature Over the Past 30
      Years.
AB  - BACKGROUND: Endoprosthetic replacement has become the mainstream method of
      reconstruction after tumor resection around the knee for decades, but there is a
      lack of comprehensive review evaluating the implant outcomes. We performed a
      systematic review to analyze the implant survival and complication profiles of
      distal femoral replacement (DFR) and proximal tibial replacement (PTR) in adults,
      and to evaluate the effects of different fixation methods and hinge mechanisms.
      METHODS: A systematic review of 40 studies with 4748 DFR cases and 1713 PTR cases
      was performed after searching the PubMed and EMBASE databases. Results of the
      implant longevity, complications, and other relevant data were extracted,
      recategorized, and analyzed. An additional review of 227 cases of Compress DFR
      from 6 studies was also performed. RESULTS: The mean 5-, 10-, 15-, and 20-year
      implant survival rates of DFR were 78.3%, 70.1%, 61.6%, and 38.3%, slightly
      higher than those of PTR (75%, 60%, 55.3%, and 25.1%). Aseptic loosening (8.8%)
      and infection (8.5%) were the most devastating complications in DFR, while in PTR
      it was infection (16.8%). Cemented or cementless fixation did not significantly
      affect implant survival or aseptic loosening rate. Rotating-hinge mechanism might
      improve long-term implant survival and reduce bushing wear, but not necessarily
      prevented aseptic loosening. The series Kotz modular femur and tibia replacement
      system/Howmedica modular replacement system/global modular replacement system was
      one of the most durable implants. The Compress DFR showed no superiority in
      implant survival and complication profiles over other brands of endoprostheses.
      CONCLUSION: Short-term to mid-term implant survival of adult tumor endoprostheses
      around the knee is acceptable but long-term outcome remains unsatisfactory.
      Efforts should be made in reducing loosening and infection.

PMID- 29191446
TI  - The efficiency of database searches for creating systematic reviews was improved
      by search filters.
AB  - OBJECTIVES: To compare Clinical Queries (CQs) for randomized trials of therapy
      'methods' and 'NOT' limits search filters with Cochrane methods filters. STUDY
      DESIGN AND SETTING: Analytic survey of Cochrane reviews as the reference standard
      for retrieving studies included in the reviews ("included studies [ISs]"). The
      sensitivity and precision of Cochrane content terms + Cochrane methods terms were
      compared in MEDLINE and Embase with Cochrane content terms + CQs maximally
      sensitive filter for therapy studies, without and with additional 'NOT' limits
      (CQ-S [CQ sensitive]; CQ-S + limits) and a balanced filter without and with
      additional NOT limits (CQ-B [CQ balanced]; CQ-B + limits). RESULTS: Cochrane or
      CQ methods terms reduced, by 64-96%, the overall retrieval of articles with
      minimal loss of ISs. Sensitivity was high and similar for the 4 filters. However,
      CQ-B + limits had the highest precision (2.64%, number needed to be read to find
      one eligible study [NNR] 38) followed by the CQ-B (1.05%, NNR 95), Cochrane
      search (0.51%, NNR 198), CQ-S + limits (0.34%, NNR 296), and CQ-S filters (0.31%,
      NNR 325). CONCLUSION: For systematic reviews of therapeutic interventions, the
      efficiency of searches in MEDLINE and Embase was better served by the CQs for
      therapy studies with balanced methods filter and NOT limits.

PMID- 29191445
TI  - Training health professionals to recruit into challenging randomized controlled
      trials improved confidence: the development of the QuinteT randomized controlled
      trial recruitment training intervention.
AB  - OBJECTIVES: The objective of this study was to describe and evaluate a training
      intervention for recruiting patients to randomized controlled trials (RCTs),
      particularly for those anticipated to be difficult for recruitment. STUDY DESIGN
      AND SETTING: One of three training workshops was offered to surgeons and one to
      research nurses. Self-confidence in recruitment was measured through
      questionnaires before and up to 3 months after training; perceived impact of
      training on practice was assessed after. Data were analyzed using two-sample t
      tests and supplemented with findings from the content analysis of free-text
      comments. RESULTS: Sixty-seven surgeons and 32 nurses attended. Self-confidence
      scores for all 10 questions increased after training [range of mean scores before
      5.1-6.9 and after 6.9-8.2 (scale 0-10, all 95% confidence intervals are above 0
      and all P-values <0.05)]. Awareness of hidden challenges of recruitment following
      training was high-surgeons' mean score 8.8 [standard deviation (SD), 1.2] and
      nurses' 8.4 (SD, 1.3) (scale 0-10); 50% (19/38) of surgeons and 40% (10/25) of
      nurses reported on a 4-point Likert scale that training had made "a lot" of
      difference to their RCT discussions. Analysis of free text revealed this was
      mostly in relation to how to convey equipoise, explain randomization, and manage
      treatment preferences. CONCLUSION: Surgeons and research nurses reported
      increased self-confidence in discussing RCTs with patients, a raised awareness of
      hidden challenges and a positive impact on recruitment practice following QuinteT
      RCT Recruitment Training. Training will be made more available and evaluated in
      relation to recruitment rates and informed consent.

PMID- 29191447
TI  - Comparative evidence on harms in pediatric randomized clinical trials from less
      developed versus more developed countries is limited.
AB  - OBJECTIVES: Evaluate comparative harm rates from medical interventions in
      pediatric randomized clinical trials (RCTs) from more developed (MDCs) and less
      developed countries (LDCs). STUDY DESIGN AND SETTING: Meta-epidemiologic
      empirical evaluation of Cochrane Database of Systematic Reviews (June 2014) meta
      analyses reporting clinically important harm-outcomes (severe adverse events
      [AEs], discontinuations due to AEs, any AE, and mortality) that included at least
      one pediatric RCT from MDCs and at least one from LDCs. We estimated relative
      odds ratios (RORs) for each harm, within each meta-analysis, between RCTs from
      MDCs and LDCs and calculated random-effects-summary-RORs (sRORs) for each harm
      across multiple meta-analyses. RESULTS: Only 1% (26/2,363) of meta-analyses with
      clinically important harm-outcomes in the entire Cochrane Database of Systematic
      Reviews included pediatric RCTs both from MDCs and LDCs. We analyzed 26 meta
      analyses with 244 data sets from pediatric RCTs, 116 from MDCs and 128 from LDCs
      (64 and 66 unique RCTs respectively). The summary ROR was 0.92 (95% confidence
      intervals: 0.78-1.08) for severe AEs; 1.13 (0.54-2.34) for discontinuations due
      to AEs; 1.10 (0.77-1.59) for any AE; and 0.99 (0.61-1.61) for mortality and for
      the all-harms-combined-end point 0.96 (0.83-1.10). Differences of ROR-point
      estimates >=2-fold between MDCs and LDCs were identified in 35% of meta-analyses.
      CONCLUSION: We found no major systematic differences in harm rates in pediatric
      trials between MDCs and LDCs, but data on harms in children were overall very
      limited.

PMID- 29191448
TI  - Adverse perinatal outcomes associated with crown-rump length discrepancy in in
      vitro fertilization pregnancies.
AB  - OBJECTIVE(S): To determine whether an association exists between small crown-rump
      length (CRL) and adverse obstetrical outcomes in pregnancies conceived by IVF and
      to compare a CRL reference based on IVF pregnancies to a reference based on
      spontaneous pregnancies. DESIGN: Retrospective cohort study. CRL was classified
      as small by comparing it with the local university hospital maternal fetal
      medicine standard and the Monash IVF reference chart. SETTING: University
      affiliated fertility center. PATIENT(S): Singleton pregnancies conceived by IVF
      with ultrasounds performed between 7+0 and 8+6 weeks of gestational age.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy loss, preterm birth,
      and low birth weight. RESULT(S): Included were 940 clinical pregnancies. The
      overall and CRL-discrepant miscarriage rates were 12.7% and 41%, respectively.
      When CRL was small, the maternal age-adjusted odds of miscarriage were 13.8 times
      higher (95% confidence interval [CI], 8.9-21.6). At age 30, small CRL was
      associated with a 30% risk of miscarriage, versus 61% at age 45. There was no
      association between small CRL and preterm birth or low birth weight. The
      sensitivity and specificity for predicting miscarriage from the optimal Monash
      cut point were 0.69 (95% CI, 0.61-0.77) and 0.84 (95% CI, 0.82-0.87), which were
      similar to those of the CRL reference based on spontaneous pregnancies.
      CONCLUSION(S): Small CRL in IVF pregnancy was strongly associated with
      miscarriage, especially in the context of advanced maternal age. Small CRL was
      not associated with preterm birth or low birth weight. A CRL reference based on
      IVF pregnancies was equivalent to the standard reference for predicting
      miscarriage.

PMID- 29191449
TI  - Extent of chromosomal mosaicism influences the clinical outcome of in vitro
      fertilization treatments.
AB  - OBJECTIVE: To assess whether the extent of chromosomal mosaicism can influence
      the success rate of IVF treatments. DESIGN: Prospective study. SETTING: Private
      genetic and assisted reproduction centers. PATIENT(S): The transfer of mosaic
      embryos was offered to 77 women for which IVF resulted in no euploid embryos
      available for transfer. INTERVENTION(S): All embryos were cultured to blastocyst
      stage; trophectoderm biopsy was performed on day 5/6 of development.
      Comprehensive chromosome screening was performed using either next-generation
      sequencing or array-comparative genomic hybridization methodologies. MAIN OUTCOME
      MEASURE(S): The clinical outcome obtained after transfer of mosaic embryos with
      low (<50%) and high (>=50%) aneuploidy percentage was compared with that
      resulting from a control group of 251 euploid blastocysts. RESULT(S): A
      significantly higher implantation rate (48.9% vs. 24.2%), clinical pregnancy
      rate/ET (40.9% vs. 15.2%), and live-birth rate (42.2% vs. 15.2%) were observed
      comparing embryos with mosaicism <50% and >=50%. Mosaic embryos with high
      aneuploidy percentage (>=50%) showed a significantly lower clinical pregnancy
      rate/ET (15.2% vs. 46.4%), implantation rate (24.4% vs. 54.6%), and live-birth
      rate (15.2% vs. 46.6%) than euploid blastocysts. In contrast, embryos with lower
      aneuploidy percentage (<50%) have a clinical outcome similar to euploid embryos.
      CONCLUSION(S): The results of this study further confirm that mosaic embryos can
      develop into healthy euploid newborns. We demonstrated that the extent of
      mosaicism influences the IVF success rate. Mosaic embryos with low aneuploidy
      percentage have higher chances of resulting in the birth of healthy babies
      compared with embryos with higher mosaicism levels.

PMID- 29191450
TI  - Comparative Bioavailability of Hydroxyprogesterone Caproate Administered via
      Intramuscular Injection or Subcutaneous Autoinjector in Healthy Postmenopausal
      Women: A Randomized, Parallel Group, Open-label Study.
AB  - PURPOSE: The purpose of this study was to evaluate the bioavailability of
      hydroxyprogesterone caproate (HPC) administered as a subcutaneous injection in
      the back of the upper arm using a prefilled autoinjector syringe with a 27-gauge
      needle compared with standard intramuscular injection in the gluteus maximus
      using a 21-gauge needle. METHODS: Healthy postmenopausal women 50 to 75 years old
      were randomized in a parallel group design to receive a single SC injection of
      1.1 mL (275-mg total dose) of preservative-free HPC administered using an
      autoinjector in the back of the upper arm or a single IM injection of 1 mL (250
      mg total dose) of preservative-free HPC administered in the gluteus maximus.
      Blood samples were collected through 1008 hours (42 days) after injection. The
      primary measures were the Cmax, AUC0-t, and AUC0-infinity. Secondary measures
      were Tmax, ke, t1/2, and injection site reactions captured as a treatment
      emergent adverse event. FINDINGS: The pharmacokinetic population consisted of 90
      individuals; 45 received subcutaneous administration and 45 received
      intramuscular administration. Geometric mean whole blood concentrations of HPC
      were comparable between administration regimens. Subcutaneous administration
      resulted in a higher geometric mean Cmax than intramuscular administration (7.88
      vs 6.91 ng/mL), but median Tmax values were comparable (48.1 vs 49.7 hours). The
      least square geometric mean ratios for AUC0-168), AUC0-t, and AUC0-infinity were
      102.89%, 110.25%, and 113.51%, respectively, with all 90% CIs within the 80.0% to
      125.0% window that defined bioequivalence. The ratio for Cmax was 113.95% with a
      90% CI of 91.94% to 141.23% but with substantial overlap of individual values
      between administration regimens. The geometric mean t1/2 of HPC was 212 hours for
      the subcutaneous administration and 188 hours for the intramuscular
      administration. The most common treatment-emergent adverse event was injection
      site pain (subcutaneous, 37.3%; intramuscular, 8.2%), described as mild (85%) to
      moderate (15%). IMPLICATIONS: Administration of HPC by SC injection of 1.1 mL
      (275 mg) via autoinjector is bioequivalent to IM injection of 1.0 mL (250 mg).
      ClinicalTrials.gov identifier: NCT02940522.

PMID- 29191451
TI  - Unfolding the mechanism of cisplatin induced pathophysiology in spleen and its
      amelioration by carnosine.
AB  - cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is
      widely used for the treatment of various types of solid tumors. Bio-distribution
      of cisplatin to other organs due to poor targeting towards only cancer cells
      constitutes the backbone of cisplatin-induced toxicity. The adverse effect of
      this drug on spleen is not well characterized so far. Therefore, we have set our
      goal to explore the mechanism of the cisplatin-induced pathophysiology of the
      spleen and would also like to evaluate whether carnosine, an endogenous
      neurotransmitter and antioxidant, can ameliorate this pathophysiological
      response. We found a dose and time-dependent increase of the pro-inflammatory
      cytokine, TNF-alpha, in the spleen tissue of the experimental mice exposed to 10
      and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can
      be attributed to the activation of the transcription factor, NF-KB. This also
      aids in the transcription of other pro-inflammatory cytokines and cellular
      adhesion molecules. Exposure of animals to cisplatin at both the doses resulted
      in ROS and NO production leading to oxidative stress. The MAP Kinase pathway,
      especially JNK activation, was also triggered by cisplatin. Eventually, the
      persistence of inflammatory response and oxidative stress lead to apoptosis
      through extrinsic pathway. Carnosine has been found to restore the expression of
      inflammatory molecules and catalase to normal levels through inhibition of pro
      inflammatory cytokines, oxidative stress, NF-KB and JNK. Carnosine also protected
      the splenic cells from apoptosis. Our study elucidated the detailed mechanism of
      cisplatin-induced spleen toxicity and use of carnosine as a protective agent
      against this cytotoxic response.

PMID- 29191452
TI  - Hesperidin attenuates iron-induced oxidative damage and dopamine depletion in
      Drosophila melanogaster model of Parkinson's disease.
AB  - This study has evaluated the action of flavonoid hesperidin on the neurotoxic
      effects caused by the intake of iron (Fe) in Drosophila melanogaster. Male adult
      flies, aged 1-3 days, have been divided into four groups of 50 each: (1) control,
      (2) Hsd 10 MUM, (3) Fe 20 mM (4) Hsd 10 MUM + Fe 20 mM. During the exposure
      protocol, the flies have been exposed to a diet containing Hsd and/or Fe for 48
      h. The survival and behavioral analyses have been carried out in vivo, and ex
      vivo. The analyses involved acetylcholinesterase (AChE) activity and Fe levels in
      the flies' heads and bodies and determination of dopaminergic levels, cellular
      and mitochondrial viability, activities of superoxide dismutase (SOD), catalase
      (CAT), glutathione-S-transferase (GST), reactive species levels (RS),
      thiobarbituric acid reactive substances (TBARS) and contents of total thiols and
      non-proteic thiols (NPSH) in the flies' heads. A significant negative correlation
      between Fe levels in the head of the flies and the survival, dopamine levels and
      antioxidant enzymes in the head of the flies has been found. Additionally,
      significant positive correlation between Fe levels in the head of the flies with
      negative geotaxis RS and AChE activity in the head of the flies has been found.
      It demonstrates that the flies which had higher levels of Fe in their heads have
      demonstrated more susceptibility to neurotoxicity. An important result from our
      study is that Hsd treatment promotes a decrease in Fe concentration in the head,
      restores dopamine levels and cholinergic activity of the flies and improves motor
      function caused by Fe. Hsd also ameliorates Fe induced mortality, oxidative
      stress and mitochondrial dysfunction. Our results have demonstrated the
      neuroprotective effect of Hsd and it suggests that flavonoid acts in different
      ways to protect against the Parkinson disease caused by Fe exposure such as the
      direct scavenging of RS and activation of antioxidant enzymes.

PMID- 29191453
TI  - Apigenin sensitizes hepatocellular carcinoma cells to doxorubic through
      regulating miR-520b/ATG7 axis.
AB  - Chemo-resistance is a serious obstacle for successful treatment of cancer.
      Apigenin, a dietary flavonoid, has been reported as an anticancer drug in various
      malignant cancers. This study aimed to investigate the potential chemo
      sensitization effect of apigenin in doxorubicin-resistant hepatocellular
      carcinoma cell line BEL-7402/ADM. We observed that apigenin significantly
      enhanced doxorubicin sensitivity, induced miR-520b expression and inhibited ATG7
      dependent autophagy in BEL-7402/ADM cells. In addition, we also showed that miR
      520b mimics increased doxorubicin sensitivity and inhibited ATG7-dependent
      autophagy. Meanwhile, we indicated that ATG7 was a potential target of miR-520b.
      Furthermore, APG inhibited the growth of hepatocellar carcinoma xenografts in
      nude mice by up-regulating miR-520b and inhibiting ATG7. Our finding provides
      evidence that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR
      520b/ATG7 pathway, which furtherly supports apigenin as a potential chemo
      sensitizer for hepatocellular carcinoma.

PMID- 29191454
TI  - Fullerene (C60) particle size implications in neurotoxicity following infusion
      into the hippocampi of Wistar rats.
AB  - The buckminsterfullerene (C60) is considered as a relevant candidate for drug and
      gene delivery to the brain, once it has the ability to cross the blood-brain
      barrier. However, the biological implications of this nanomaterial are not fully
      understood, and its safety for intracerebral delivery is still debatable. In this
      study, we investigated if C60 particle size could alter its biological effects.
      For this, two aqueous C60 suspensions were used with maximum particle size up to
      200nm and 450nm. The suspensions were injected in the hippocampus, the main brain
      structure involved in memory processing and spatial localization. In order to
      assess spatial learning, male Wistar rats were tested in Morris water maze, and
      the hippocampal BDNF protein levels and gene expression were analyzed. Animals
      treated with C60 up to 450nm demonstrated impaired spatial memory with a
      significant decrease in BDNF protein levels and gene expression. However, an
      enhanced antioxidant capacity was observed in both C60 treatments. A decrease in
      reactive oxygen species levels was observed in the treatments with suspensions
      containing particles measuring with up to 450nm. Thiobarbituric acid reactive
      substances, glutamate cysteine ligase, and glutathione levels showed no
      alterations among the different treatments. In conclusion, different particle
      sizes of the same nanomaterial can lead to different behavioral outcomes and
      biochemical parameters in brain tissue.

PMID- 29191455
TI  - ASGE EndoVators Summit: Defining the role and value of endoscopic therapies in
      obesity management.

PMID- 29191456
TI  - Impact of systemic inflammation on the relationship between insulin resistance
      and all-cause and cancer-related mortality.
AB  - BACKGROUND: Insulin resistance and inflammation play an important role in a
      variety of chronic diseases. OBJECTIVE: We investigated the influence of systemic
      inflammation on the relationship between insulin resistance and mortality risk in
      apparently healthy adults. METHODS: This study examined the mortality outcomes
      for 165,849 Koreans enrolled in a health-screening program. The subjects were
      divided into four groups according to their homeostatic model assessment of
      insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP)
      levels: group 0, HOMA-IR <75% and hs-CRP <2.0mg/L; group 1, HOMA-IR >=75% and hs
      CRP <2.0mg/L; group 2, HOMA-IR <75% and hs-CRP >=2.0mg/L; and group 3, HOMA-IR
      >=75% and hs-CRP >=2.0mg/L. The Cox proportional hazard models were used to
      assess hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause,
      cardiovascular disease, and cancer-related mortality. RESULTS: During the follow
      up period of 1,417,325.6person-years, a total of 1316 deaths (182 from
      cardiovascular disease) occurred. The multivariate-adjusted HRs for all-cause
      mortality were significantly higher in groups 2 (HR 1.40; 95% CI: 1.19-1.64) and
      group 3 (HR 1.68; 95% CI: 1.34-2.10) than that in group 0. For cardiovascular
      mortality, the sex-adjusted hazards were also significantly higher in groups 2
      and 3 than that in group 0; however, this increased risk disappeared during
      multivariate analysis. Groups 2 and 3 had significantly higher risk for cancer
      related mortality than group 0, with multivariate-adjusted hazard ratios of 1.48
      (95% CI: 1.18-1.86) and 1.84 (95% CI: 1.35-2.51), respectively. CONCLUSIONS:
      Systemic inflammation can be used to stratify the subjects according to the all
      cause and cancer-related mortality risks, irrespective of the insulin-resistance
      status. And this tendency is most pronounced in cancer-related mortality.

PMID- 29191457
TI  - The physics of small megavoltage photon beam dosimetry.
AB  - The increased interest during recent years in the use of small megavoltage photon
      beams in advanced radiotherapy techniques has led to the development of dosimetry
      recommendations by different national and international organizations. Their
      requirement of data suitable for the different clinical options available,
      regarding treatment units and dosimetry equipment, has generated a considerable
      amount of research by the scientific community during the last decade. The
      multiple publications in the field have led not only to the availability of new
      invaluable data, but have also contributed substantially to an improved
      understanding of the physics of their dosimetry. This work provides an overview
      of the most important aspects that govern the physics of small megavoltage photon
      beam dosimetry.

PMID- 29191458
TI  - Long term radiological features of radiation-induced lung damage.
AB  - PURPOSE: To describe the radiological findings of radiation-induced lung damage
      (RILD) present on CT imaging of lung cancer patients 12 months after radical
      chemoradiation. MATERIAL AND METHODS: Baseline and 12-month CT scans of 33
      patients were reviewed from a phase I/II clinical trial of isotoxic
      chemoradiation (IDEAL CRT). CT findings were scored in three categories derived
      from eleven sub-categories: (1) parenchymal change, defined as the presence of
      consolidation, ground-glass opacities (GGOs), traction bronchiectasis and/or
      reticulation; (2) lung volume reduction, identified through reduction in lung
      height and/or distortions in fissures, diaphragm, anterior junction line and
      major airways anatomy, and (3) pleural changes, either thickening and/or
      effusion. RESULTS: Six patients were excluded from the analysis due to anatomical
      changes caused by partial lung collapse and abscess. All remaining 27 patients
      had radiological evidence of lung damage. The three categories, parenchymal
      change, shrinkage and pleural change were present in 100%, 96% and 82%
      respectively. All patients had at least two categories of change present and 72%
      all three. GGOs, reticulation and traction bronchiectasis were present in 44%,
      52% and 37% of patients. CONCLUSIONS: Parenchymal change, lung shrinkage and
      pleural change are present in a high proportion of patients and are frequently
      identified in RILD. GGOs, reticulation and traction bronchiectasis are common at
      12 months but not diagnostic.

PMID- 29191459
TI  - Impact of real-time metabolomics in liver transplantation: Graft evaluation and
      donor-recipient matching.
AB  - BACKGROUND & AIMS: There is an emerging need to assess the metabolic state of
      liver allografts especially in the novel setting of machine perfusion
      preservation and donor in cardiac death (DCD) grafts. High-resolution magic-angle
      spinning nuclear magnetic resonance (HR-MAS-NMR) could be a useful tool in this
      setting as it can extemporaneously provide untargeted metabolic profiling. The
      purpose of this study was to evaluate the potential value of HR-MAS-NMR
      metabolomic analysis of back-table biopsies for the prediction of early allograft
      dysfunction (EAD) and donor-recipient matching. METHOD: The metabolic profiles of
      back-table biopsies obtained by HR-MAS-NMR, were compared according to the
      presence of EAD using partial least squares discriminant analysis. Network
      analysis was used to identify metabolites which changed significantly. The
      profiles were compared to native livers to identify metabolites for donor
      recipient matching. RESULTS: The metabolic profiles were significantly different
      in grafts that caused EAD compared to those that did not. The constructed model
      can be used to predict the graft outcome with excellent accuracy. The metabolites
      showing the most significant differences were lactate level >8.3 mmol/g and
      phosphocholine content >0.646 mmol/g, which were significantly associated with
      graft dysfunction with an excellent accuracy (AUROClactates = 0.906;
      AUROCphosphocholine = 0.816). Native livers from patients with sarcopenia had low
      lactate and glycerophosphocholine content. In patients with sarcopenia, the risk
      of EAD was significantly higher when transplanting a graft with a high-risk graft
      metabolic score. CONCLUSION: This study underlines the cost of metabolic
      adaptation, identifying lactate and choline-derived metabolites as predictors of
      poor graft function in both native livers and liver grafts. HR-MAS-NMR seems a
      valid technique to evaluate graft quality and the consequences of cold ischemia
      on the graft. It could be used to assess the efficiency of graft resuscitation on
      machine perfusion in future studies. LAY SUMMARY: Real-time metabolomic profiles
      of human grafts during back-table can accurately predict graft dysfunction. High
      lactate and phosphocholine content are highly predictive of graft dysfunction
      whereas low lactate and phosphocholine content characterize patients with
      sarcopenia. In these patients, the cost of metabolic adaptation may explain the
      poor outcomes.

PMID- 29191460
TI  - The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share
      their E2 and E3 components for their function and both generate reactive oxygen
      species.
AB  - Herein are reported unique properties of the novel human thiamin diphosphate
      (ThDP)-dependent enzyme 2-oxoadipate dehydrogenase (hE1a), known as dehydrogenase
      E1 and transketolase domain-containing protein 1 that is encoded by the DHTKD1
      gene. It is involved in the oxidative decarboxylation of 2-oxoadipate (OA) to
      glutaryl-CoA on the final degradative pathway of L-lysine and is critical for
      mitochondrial metabolism. Functionally active recombinant hE1a has been produced
      according to both kinetic and spectroscopic criteria in our toolbox leading to
      the following conclusions: (i) The hE1a has recruited the dihydrolipoyl
      succinyltransferase (hE2o) and the dihydrolipoyl dehydrogenase (hE3) components
      of the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex (OGDHc) for
      its activity. (ii) 2-Oxoglutarate (OG) and 2-oxoadipate (OA) could be oxidized by
      hE1a, however, hE1a displays an approximately 49-fold preference in catalytic
      efficiency for OA over OG, indicating that hE1a is specific to the 2-oxoadipate
      dehydrogenase complex. (iii) The hE1a forms the ThDP-enamine radical from OA
      according to electron paramagnetic resonance detection in the oxidative half
      reaction, and could produce superoxide and H2O2 from decarboxylation of OA in the
      forward physiological direction, as also seen with the 2-oxoglutarate
      dehydrogenase hE1o component. (iv) Once assembled to complex with the same hE2o
      and hE3 components, the hE1o and hE1a display strikingly different regulation:
      both succinyl-CoA and glutaryl-CoA significantly reduced the hE1o activity, but
      not the activity of hE1a.

PMID- 29191461
TI  - Endoplasmic reticulum stress precedes oxidative stress in antibiotic-induced
      cholestasis and cytotoxicity in human hepatocytes.
AB  - Endoplasmic reticulum (ER) stress has been associated with various drug-induced
      liver lesions but its participation in drug-induced cholestasis remains unclear.
      We first aimed at analyzing liver damage caused by various hepatotoxic
      antibiotics, including three penicillinase-resistant antibiotics (PRAs), i.e.
      flucloxacillin, cloxacillin and nafcillin, as well as trovafloxacin, levofloxacin
      and erythromycin, using human differentiated HepaRG cells and primary
      hepatocytes. All these antibiotics caused early cholestatic effects typified by
      bile canaliculi dilatation and reduced bile acid efflux within 2h and dose
      dependent enhanced caspase-3 activity within 24h. PRAs induced the highest
      cholestatic effects at non cytotoxic concentrations. Then, molecular events
      involved in these lesions were analyzed. Early accumulation of misfolded proteins
      revealed by thioflavin-T fluorescence and associated with phosphorylation of the
      unfolded protein response sensors, eIF2alpha and/or IRE1alpha, was evidenced with
      all tested hepatotoxic antibiotics. Inhibition of ER stress markedly restored
      bile acid efflux and prevented bile canaliculi dilatation. Downstream of ER
      stress, ROS were also generated with high antibiotic concentrations. The
      protective HSP27-PI3K-AKT signaling pathway was activated only in PRA-treated
      cells and its inhibition increased ROS production and aggravated caspase-3
      activity. Overall, our results demonstrate that (i) various antibiotics reported
      to cause cholestasis and hepatocellular injury in the clinic can also induce such
      effects in in vitro human hepatocytes; (ii) PRAs cause the strongest cholestatic
      effects in the absence of cytotoxicity; (iii) cholestatic features occur early
      through ER stress; (iv) cytotoxic lesions are observed later through ER stress
      mediated ROS generation; and (v) activation of the HSP27-PI3K-AKT pathway
      protects from cytotoxic damage induced by PRAs only.

PMID- 29191462
TI  - Exposure of tropoelastin to peroxynitrous acid gives high yields of nitrated
      tyrosine residues, di-tyrosine cross-links and altered protein structure and
      function.
AB  - Elastin is an abundant extracellular matrix protein in elastic tissues, including
      the lungs, skin and arteries, and comprises 30-57% of the aorta by dry mass. The
      monomeric precursor, tropoelastin (TE), undergoes complex processing during
      elastogenesis to form mature elastic fibres. Peroxynitrous acid (ONOOH), a potent
      oxidising and nitrating agent, is formed in vivo from superoxide and nitric oxide
      radicals. Considerable evidence supports ONOOH formation in the inflamed artery
      wall, and a role for this species in the development of human atherosclerotic
      lesions, with ONOOH-damaged extracellular matrix implicated in lesion rupture. We
      demonstrate that TE is highly sensitive to ONOOH, with this resulting in
      extensive dimerization, fragmentation and nitration of Tyr residues to give 3
      nitrotyrosine (3-nitroTyr). This occurs with equimolar or greater levels of
      oxidant and increases in a dose-dependent manner. Quantification of Tyr loss and
      3-nitroTyr formation indicates extensive Tyr modification with up to two modified
      Tyr per protein molecule, and up to 8% conversion of initial ONOOH to 3-nitroTyr.
      These effects were modulated by bicarbonate, an alternative target for ONOOH.
      Inter- and intra-protein di-tyrosine cross-links have been characterized by mass
      spectrometry. Examination of human atherosclerotic lesions shows colocalization
      of 3-nitroTyr with elastin epitopes, consistent with TE or elastin modification
      in vivo, and also an association of 3-nitroTyr containing proteins and elastin
      with lipid deposits. These data suggest that exposure of TE to ONOOH gives marked
      chemical and structural changes to TE and altered matrix assembly, and that such
      damage accumulates in human arterial tissue during the development of
      atherosclerosis.

PMID- 29191463
TI  - Raphe Pallidus is Not Important to Central Chemoreception in a Rat Model of
      Parkinson's Disease.
AB  - Central chemoreceptors are primarily sensitive to changes in CO2/H+, and such
      changes lead to intense breathing activity. Medullary raphe and retrotrapezoid
      nucleus (RTN) neurons are candidates for central chemoreceptors because they are
      unusually pH sensitive. The pathophysiology of Parkinson's disease (PD) is
      related to the reduction of neurons in the substantia nigra pars compacta (SNpc)
      that express dopamine, although other neurons can also be degenerated in this
      pathology. In rodent models of PD, we showed an impairment of the hypercapnia
      ventilatory response due to a reduction in the number of RTN chemosensitive
      neurons. Here, we aimed to investigate if serotonine-expressing neurons in the
      Raphe pallidus/parapyramidal region (RPa/PPy) are also involved in the modulation
      of breathing during central chemoreception activation in a PD animal model. PD
      was induced in male Wistar rats with bilateral injection of 6-OHDA (6
      hydroxydopamine; 24 ug/ul) into the striatum, which leads to a reduction in the
      catecholaminergic neurons of the SNpc by 89%. In PD animals, we noticed a
      reduction in the number of RPa neurons that project to the RTN, without a change
      in the number of hypercapnia-activated (7% CO2) raphe neurons. The PD animals
      that received injection of the toxin saporin anti-SERT into the RPA/PPy region
      did not show a further reduction of respiratory frequency (fR) or ventilation
      (VE) at rest or during hypercapnia challenge. These experiments demonstrate that
      serotonergic neurons of RPa/PPy are not involved in the breathing responses
      induced by central chemoreceptor activation in a PD animal model.

PMID- 29191464
TI  - Bombyx ortholog of the Drosophila eye color gene brown controls riboflavin
      transport in Malpighian tubules.
AB  - The Drosophila eye color gene brown is known to control the transport of
      pteridine precursors in adult eyes. The Brown protein belongs to the ATP-binding
      cassette (ABC) transporter G family, which includes proteins encoded by the genes
      brown, scarlet, and white. These genes are responsible for pigmentation in
      Drosophila and the domestic silkworm Bombyx mori. Although orthologs of brown are
      conserved among insects, the function of this gene is only known in Drosophila.
      Here, we elucidated the function of the B. mori ortholog Bm-brown. We examined
      the spatial and temporal expression profiles of Bm-brown and found that this gene
      was specifically and continuously expressed in larval Malpighian tubules (MTs),
      indicating this gene has a special function in MTs. We then successfully obtained
      a Bm-brown knockout (KO) strain based on a wild-type (WT) strain using the
      clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated nuclease 9 (Cas9) system. We found that larval MTs of the KO strain
      were white, whereas those of WT were yellow. It is known that larval yellow MTs
      of WT are due to the accumulation of riboflavin. Therefore, we compared the
      riboflavin contents of MTs of KO and WT strains, and found that the riboflavin
      level in the KO strain was 20 fold less than that in WT during the 5th instar
      period. MTs are known to exhibit a similar milky color in w-3 mutant larvae due
      to a deficiency of riboflavin accumulation. The responsible gene for w-3 mutant
      is the Bmwh3 gene, which is orthologous to Drosophila white. Thus, we speculate
      that Bm-brown is heterodimerized with Bmwh3, similar to Brown/White in
      Drosophila, and acts as a riboflavin transporter in silkworm MTs.

PMID- 29191465
TI  - Crystal structure of ryanodine receptor N-terminal domain from Plutella
      xylostella reveals two potential species-specific insecticide-targeting sites.
AB  - Ryanodine receptors (RyRs) are large calcium-release channels located in
      sarcoplasmic reticulum membrane. They play a central role in excitation
      contraction coupling of muscle cells. Three commercialized insecticides targeting
      pest RyRs generate worldwide sales over 2 billion U.S. dollars annually, but the
      structure of insect RyRs remains elusive, hindering our understanding of the mode
      of action of RyR-targeting insecticides and the development of insecticide
      resistance in pests. Here we present the crystal structure of RyR N-terminal
      domain (NTD) (residue 1-205) at 2.84 A resolution from the diamondback moth
      (DBM), Plutella xylostella, a destructive pest devouring cruciferous crops all
      over the world. Similar to its mammalian homolog, DBM RyR NTD consists of a beta
      trefoil folding motif and a flanking alpha helix. Interestingly, two regions in
      NTD interacting with neighboring domains showed distinguished conformations in
      DBM relative to mammalian RyRs. Using homology modeling and molecular dynamics
      simulation, we created a structural model of the N-terminal three domains,
      showing two unique binding pockets that could be targeted by potential species
      specific insecticides. Thermal melt experiment showed that the stability of DBM
      RyR NTD was higher than mammalian RyRs, probably due to a stable intra-domain
      disulfide bond observed in the crystal structure. Previously DBM NTD was shown to
      be one of the two critical regions to interact with insecticide flubendiamide,
      but isothermal titration calorimetry experiments negated DBM NTD alone as a major
      binding site for flubendiamide.

PMID- 29191466
TI  - Synovial fluid multiplex PCR is superior to culture for detection of low-virulent
      pathogens causing periprosthetic joint infection.
AB  - INTRODUCTION: Analysis of joint aspirate is the standard preoperative
      investigation for diagnosis of periprosthetic joint infection (PJI). We compared
      the diagnostic performance of culture and multiplex polymerase chain reaction
      (PCR) of synovial fluid for diagnosis of PJI. PATIENTS AND METHODS: Patients in
      whom aspiration of the prosthetic hip or knee joint was performed before revision
      arthroplasty were prospectively included. The performance of synovial fluid
      culture and multiplex PCR was compared by McNemar's chi-squared test. RESULTS: A
      total of 142 patients were included, 82 with knee and 60 with hip prosthesis. PJI
      was diagnosed in 77 patients (54%) and aseptic failure in 65 patients (46%). The
      sensitivity of synovial fluid culture and PCR was 52% and 60%, respectively,
      showing concordant results in 116 patients (82%). In patients with PJI, PCR
      missed 6 high-virulent pathogens (S. aureus, streptococci, E. faecalis, E. coli)
      which grew in synovial fluid culture, whereas synovial fluid culture missed 12
      pathogens detected by multiplex PCR, predominantly low-virulent pathogens
      (Cutibacterium acnes and coagulase-negative staphylococci). In patients with
      aseptic failure, PCR detected 6 low-virulent organisms (predominantly C. acnes).
      CONCLUSION: While the overall performance of synovial fluid PCR was comparable to
      culture, PCR was superior for detection of low-virulent bacteria such as
      Cutibacterium spp. and coagulase-negative staphylococci. In addition, synovial
      fluid culture required several days for growth, whereas multiplex PCR provided
      results within 5hours in an automated manner.

PMID- 29191467
TI  - 2017 ACC/HRS Lifelong Learning Statement for Clinical Cardiac Electrophysiology
      Specialists: A Report of the ACC Competency Management Committee.

PMID- 29191468
TI  - Malunion of post-traumatic thoracolumbar fractures.
AB  - Thoracolumbar malunion is the result of loss of correction, insufficient
      correction or even no correction (both in the frontal and sagittal planes) of a
      thoracolumbar fracture. The main causes are incorrect assessment of the
      fracture's complexity (burst fracture), its potential progression to kyphosis and
      associated disc or ligament damage. It can also be the result of a poorly
      conducted initial treatment. The types of malunion have changed over the years
      because of the introduction of vertebroplasty and kyphoplasty. The malunion can
      be well tolerated if there is only a moderate deformity. However, the functional
      and pain-related limitations can be severe with large deformities. Functional
      limitation is mainly related to sagittal imbalance, but also to sequelae
      associated with the injury in various ways (non-union, disc degeneration, spinal
      cord compression, syringomyelia, etc.). The deformity and its consequences are
      evaluated globally using full-body standing radiographs (EOS), CT scan and MRI.
      Comparison of MRI images taken in a lying position to weight bearing views or
      even dynamic ones is an additional means to evaluate whether the lesions are
      reducible. Differences in spine morphology and compensatory mechanisms to combat
      the sagittal imbalance induced by the deformity must also be analyzed. These
      provide more complete information about the consequences of the malunion and help
      to establish the best corrective strategy. These compensatory mechanisms consist
      of accentuation of lumbar lordosis along with reduction of thoracic kyphosis. As
      a last resort, the pelvis and femur contribute to this compensation when there is
      a large deformity or a stiff spine due to preexisting osteoarthritis. Treatment
      strategies are fairly well standardized. When the deformity is reducible, a two
      stage surgery is indicated. When the deformity is not reducible, posterior
      transpedicular closed wedge osteotomy is the gold standard. Nevertheless, the
      best way to treat thoracolumbar malunion is to prevent it.

PMID- 29191469
TI  - Role of anterolateral reconstruction in patients undergoing anterior cruciate
      ligament reconstruction.
AB  - There is renewed interest in anterolateral reconstruction (ALR) for patients
      undergoing anterior cruciate ligament (ACL) reconstruction. This is the result of
      isolated ACL reconstruction and double-bundle reconstruction providing inadequate
      control over the pivot shift, and recent anatomical and biomechanical studies on
      the anterolateral ligament (ALL) and its role in the knee's rotational stability.
      From a technical point of view, ALR can be performed either as a continuity of
      the intra-articular ACL reconstruction or an independent procedure. The typical
      peripheral grafts (gracilis and semitendinosus tendons, iliotibial band) can be
      used. The femoral tunnel must be posterior and proximal to the lateral
      epicondyle, and the tibial tunnel on a line joining Gerdy's tubercle with the
      ALL's tibial insertion. Tensioning and fixation are done with the knee near full
      extension and the tibia in neutral rotation. The ALR complication rate reported
      in older studies (pain, hematoma, scar damage) has been reduced. Relative to
      isolated ACL reconstruction, ALR does not alter the infection or stiffness rate,
      and it reduces the re-injury rate and secondary meniscal damage rate. Analysis of
      the literature has not shown an increased rate of osteoarthritis after ALR. The
      objective and functional outcomes are equal to those after isolated ACL
      reconstruction. Control over rotation is improved by adding ALR and the return to
      pivot sports appears to be more successful. While the indications must still be
      refined, ALR can be proposed to young patients undergoing ACL reconstruction who
      participate in high-intensity pivot sports, have a high-grade pivot shift or who
      have a failed ACL reconstruction.

PMID- 29191470
TI  - Optimal beam margins in linac-based VMAT stereotactic ablative body radiotherapy:
      a Pareto front analysis for liver metastases.
AB  - We explored the Pareto fronts mathematical strategy to determine the optimal
      block margin and prescription isodose for stereotactic body radiotherapy (SBRT)
      treatments of liver metastases using the volumetric-modulated arc therapy (VMAT)
      technique. Three targets (planning target volumes [PTVs] = 20, 55, and 101 cc)
      were selected. A single fraction dose of 26 Gy was prescribed (prescription dose
      [PD]). VMAT plans were generated for 3 different beam energies. Pareto fronts
      based on (1) different multileaf collimator (MLC) block margin around PTV and (2)
      different prescription isodose lines (IDL) were produced. For each block margin,
      the greatest IDL fulfilling the criteria (95% of PTV reached 100%) was considered
      as providing the optimal clinical plan for PTV coverage. Liver Dmean, V7Gy, and
      V12Gy were used against the PTV coverage to generate the fronts. Gradient indexes
      (GI and mGI), homogeneity index (HI), and healthy liver irradiation in terms of
      Dmean, V7Gy, and V12Gy were calculated to compare different plans. In addition,
      each target was also optimized with a full-inverse planning engine to obtain a
      direct comparison with anatomy-based treatment planning system (TPS) results.
      About 900 plans were calculated to generate the fronts. GI and mGI show a U
      shaped behavior as a function of beam margin with minimal values obtained with a
      +1 mm MLC margin. For these plans, the IDL ranges from 74% to 86%. GI and mGI
      show also a V-shaped behavior with respect to HI index, with minimum values at 1
      mm for all metrics, independent of tumor dimensions and beam energy. Full
      inversed optimized plans reported worse results with respect to Pareto plans. In
      conclusion, Pareto fronts provide a rigorous strategy to choose clinical optimal
      plans in SBRT treatments. We show that a 1-mm MLC block margin provides the best
      results with regard to healthy liver tissue irradiation and steepness of dose
      fallout.

PMID- 29191471
TI  - Nerve-Sparing Approach Improves Outcomes of Patients Undergoing Minimally
      Invasive Radical Hysterectomy: A Systematic Review and Meta-Analysis.
AB  - Few studies have investigated the efficacy and safety of the nerve-sparing
      approach via minimally invasive surgery for the treatment of cervical cancer. We
      aimed to review the current evidence comparing nerve-sparing minimally invasive
      radical hysterectomy (NS-MRH) with conventional minimally invasive radical
      hysterectomy (MRH). This systematic review was registered in the International
      Prospective Register of Systematic Reviews (CRD#57655). Overall, 675 patients
      were included: 350 (51.9%) and 325 (48.1%) patients undergoing MRH and NS-MRH,
      respectively. MRH was associated with a shorter operative time in comparison with
      NS-MRH (mean difference = 32.57 minutes; 95% CI, 22.87-42.48). The estimated
      blood loss (mean difference = 97.14 mL, 20.01-214.29) and transfusion rate (odds
      ratio [OR] = 0.67; 95% confidence interval [CI], 0.15-3.01) did not differ
      statistically between the 2 groups. The risk of developing intraoperative (OR =
      0.43; 95% CI, 0.08-2.23) and severe postoperative (OR = 0.63; 95% CI, 0.17-2.39)
      complications was similar between NS-MRH and MRH. Patients undergoing NS-MRH
      experienced lower voiding (OR = 0.39; 95% CI, 0.19-0.81) dysfunction rates than
      patients undergoing MRH. Moreover, a trend toward lower sexual (OR = 0.25; 95%
      CI, 0.06-1.07) and rectal (OR = 0.12; 95% CI, 0.01-1.02) issues was observed for
      patients having NS-MRH compared with patients undergoing MRH. Survival outcomes
      are not influenced by the type of surgical approach (recurrence [OR = 1.27; 95%
      CI, 0.49-3.28] and death [OR = 1.01; 95% CI, 0.36-2.83]) rates. The pooled data
      suggested that NS-MRH is equivalent to MRH for the treatment of cervical cancer
      and may be superior in reducing pelvic floor dysfunction rates. However, because
      of the low level of evidence of the included studies, further randomized trials
      are warranted.

PMID- 29191472
TI  - Peptidase neurolysin: Its function related to the brain renin-angiotensin system
      and pathophysiology of stroke. Letter to the Editor.

PMID- 29191473
TI  - Dopamine receptors and BDNF-haplotypes predict dyskinesia in Parkinson's disease.
AB  - OBJECTIVE: Dyskinesia is a known side-effect of the treatment of Parkinson's
      Disease (PD). We examined the influence of haplotypes in three dopamine receptors
      (DRD1, DRD2 and DRD3) and the Brain Derived Neurotrophic Factor (BDNF) on
      dyskinesia. METHODS: Patient data were drawn from a population-based case-control
      study. We included 418 patients with confirmed diagnoses by movement disorder
      specialists, using levodopa and a minimum three years disease duration at the
      time of assessment. Applying Haploview and Phase, we created haploblocks for DRD1
      3 and BDNF. Risk scores for DRD2 and DRD3 were generated. We calculated risk
      ratios using Poisson regression with robust error variance. RESULTS: There was no
      difference in dyskinesia prevalence among carriers of various haplotypes in DRD1.
      However, one haplotype in each DRD2 haploblocks was associated with a 29 to 50%
      increase in dyskinesia risk. For each unit increase in risk score, we observed a
      16% increase in dyskinesia risk for DRD2 (95%CI: 1.05-1.29) and a 17% (95%CI:
      0.99-1.40) increase for DRD3. The BDNF haploblock was not associated, but the
      minor allele of the rs6265 SNP was associated with dyskinesia (adjusted RR 1.31
      (95%CI: 1.01-1.70)). CONCLUSION: Carriers of DRD2 risk haplotypes and possibly
      the BDNF variants rs6265 and DRD3 haplotypes, were at increased risk of
      dyskinesia, suggesting that these genes may be involved in dyskinesia related
      pathomechanisms. PD patients with these genetic variants might be prime
      candidates for treatments aiming to prevent or delay the onset of dyskinesia.

PMID- 29191474
TI  - Chikungunya-related erosive arthritis: case report and literature review.
AB  - Chikungunya virus infection (CHIKV) is associated with joint involvement in half
      of the cases. This can lead to erosive arthritis which, given the high
      intervariability of clinical and serological presentations, and the probable role
      of genetic conditioning in the severity and chronification of the condition,
      represents a great diagnostic and therapeutic challenge. There is an important
      lack of scientific evidence that would enable us to characterize the variability
      of the patient and choose the most appropriate approach.

PMID- 29191475
TI  - Evaluation of Bruker Biotyper and Vitek MS for the identification of Candida
      tropicalis on different solid culture media.
AB  - BACKGROUND: The aim of this study was to investigate the performance of the
      Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) and Vitek MS systems for identification of
      genetically-confirmed blood isolates of Candida tropicalis that had been grown on
      several types of culture media commonly used for primary fungal isolation.
      METHODS: Isolates included 105 from the National China Hospital Invasive Fungal
      Surveillance Net program (CHIF-NET) and 120 from National Taiwan University
      Hospital (NTUH). Culture media tested for CHIF-NET isolates included trypticase
      soy agar supplemented with 5% sheep blood (BAP), Sabouraud dextrose agar (SDA-C),
      CHROMagar, China blue agar (CBA), chocolate agar supplemented with vancomycin
      (CAP-VA), and MacConkey agar (MAC). Culture media used for NTUH isolates included
      BAP, SDA, CHROMagar, eosin methylene blue (EMB), inhibitory mold agar (IMA),
      Mycosel agar, and cornmeal agar (CMA). RESULTS: The Bruker Biotyper correctly
      identified all CHIF-NET isolates to the species level on all six agar media
      tested and correctly identified the majority of NTUH isolates with the exception
      of isolates grown on SDA (85.8%) and CMA (52.5%). The Vitek MS system correctly
      identified all CHIF-NET isolates to the species level with the exception of
      isolates grown on CHROMagar (84.8%), and correctly identified the majority of
      NTUH isolates with the exception of isolates grown on SDA (51.7%), Mycosel agar
      (57.5%), and CMA (9.2%) for NTUH isolates. CONCLUSION: Clinical microbiologists
      should be aware that different culture media can affect the performance of the
      Bruker Biotyper MALDI-TOF MS and Vitek MS systems in identifying C. tropicalis.

PMID- 29191476
TI  - The association between serum uric acid and asymptomatic intracranial arterial
      stenosis in middle-aged Koreans.
AB  - BACKGROUND AND AIMS: Intracranial arterial stenosis (ICAS) is one of the most
      common causes of stroke, especially in Asians. Hyperuricemia has been associated
      with an increased risk of comorbidities such as metabolic syndrome or
      cardiovascular diseases. However, there are few studies focusing on the
      association between serum uric acid (SUA) levels and asymptomatic ICAS. The aim
      of this study was to explore the association between SUA and the prevalence of
      ICAS in middle-aged Korean health screening examinees. METHODS AND RESULTS: A
      cross-sectional study was performed on 9417 males and 7755 females who underwent
      a comprehensive health examination including transcranial Doppler (TCD)
      ultrasonography. The association of SUA and ICAS was analyzed using multivariate
      logistic regression. The prevalence of ICAS among the total examinee population
      was 3.55%. In females, the multivariate-adjusted odds ratio for ICAS was 1.52
      (confidence interval 1.13-2.04) in the 3rd quartile of SUA and 1.45 (1.05-2.00)
      in the highest quartile, compared to the reference (P for trend 0.008). This
      trend was evident in all clinically relevant subgroups evaluated, including women
      with low inflammation status. SUA was not significantly associated with the
      prevalence of ICAS among males. In a sensitivity analysis, the multivariate
      adjusted odds ratio of middle cerebral artery stenosis in females was 1.60 (1.09
      2.37) in the highest quartile compared to the reference (P for trend 0.023).
      CONCLUSIONS: Higher SUA level was associated with increased risk of ICAS among
      middle-aged females but not males. A further cohort study is warranted to
      elucidate the effect of SUA on asymptomatic ICAS.

PMID- 29191477
TI  - Improved three-dimensional multi-echo gradient echo based myelin water fraction
      mapping with phase related artifact correction.
AB  - Myelin water fraction (MWF) mapping with a multi-echo gradient echo (mGRE)
      sequence using complex-value based model fitting approach was recently described,
      in which the phase of the data plays an important role in the accuracy of the
      fitting results. Thus, influences coming from the undesirable phase components
      need to be reduced. Targeted for improved MWF mapping, methods to combat these
      phase related issues which include offset correction, main magnetic field (B0)
      inhomogeneity related correction, and flow compensation have been developed. For
      offset correction, a coil combine method with bipolar readout gradients has been
      devised. For B0 related artifact, a voxel spread function correction approach
      along with a navigator echo acquisition was utilized. Finally, flow compensation
      gradients were used to reduce the effects of flow from regions including the
      veins. The correction methods led to reduced residual fitting error and improved
      quality of the resultant MWF maps. Quantitative analysis shows increased
      reliability when the corrections were used. Data from normal volunteers showed
      improved MWF mapping with the integrated method developed in this work.

PMID- 29191478
TI  - Repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex
      modulates value-based learning during sequential decision-making.
AB  - Adaptive behavior in daily life often requires the ability to acquire and
      represent sequential contingencies between actions and the associated outcomes.
      Although accumulating evidence implicates the role of dorsolateral prefrontal
      cortex (dlPFC) in complex value-based learning and decision-making, direct
      evidence for involvements of this region in integrating information across
      sequential decision states is still scarce. Using a 3-stage deterministic Markov
      decision task, here we applied offline, inhibitory low-frequency 1-Hz repetitive
      transcranial magnetic stimulation (rTMS) over the left dlPFC in young male adults
      (n = 31, mean age = 23.8 years, SD = 2.5 years) in a within-subject cross-over
      design to study the roles of this region in influencing value-based sequential
      decision-making. In two separate sessions, each participant received 1-Hz rTMS
      stimulation either over the left dlPFC or over the vertex. The results showed
      that transiently inhibiting the left dlPFC impaired choice accuracy, particularly
      in situations in which the acquisition of sequential transitions between decision
      states and temporally lagged action-outcome contingencies played a greater role.
      Estimating parameters of a diffusion model from behavioral choices, we found that
      the diffusion drift rate, which reflects the efficiency of information
      integration, was attenuated by the stimulation. Moreover, the effects of rTMS
      interacted with session: individuals who could not efficiently integrate
      information across sequential states in the first session due to disrupted dlPFC
      function also could not catch up in performance during the second session with
      those individuals who could learn sequential transitions with intact dlPFC
      function in the first session. Taken together, our findings suggest that the left
      dlPFC is crucially involved in the acquisition of complex sequential relations
      and in the potential of such learning.

PMID- 29191479
TI  - The spatiotemporal pattern of pure tone processing: A single-trial EEG-fMRI
      study.
AB  - Although considerable research has been published on pure tone processing, its
      spatiotemporal pattern is not well understood. Specifically, the link between
      neural activity in the auditory pathway measured by functional magnetic resonance
      imaging (fMRI) and electroencephalography (EEG) markers of pure tone processing
      in the P1, N1, P2, and N4 components is not well established. In this study, we
      used single-trial EEG-fMRI as a multi-modal fusion approach to integrate
      concurrently acquired EEG and fMRI data, in order to understand the spatial and
      temporal aspects of the pure tone processing pathway. Data were recorded from 33
      subjects who were presented with stochastically alternating pure tone sequences
      with two different frequencies: 200 and 6400 Hz. Brain network correlated with
      trial-to-trial variability of the task-discriminating EEG amplitude was
      identified. We found that neural responses responding to pure tone perception are
      spatially along the auditory pathway and temporally divided into three stages:
      (1) the early stage (P1), wherein activation occurs in the midbrain, which
      constitutes a part of the low level auditory pathway; (2) the middle stage (N1,
      P2), wherein correlates were found in areas associated with the posterodorsal
      auditory pathway, including the primary auditory cortex and the motor cortex; (3)
      the late stage (N4), wherein correlation was found in the motor cortex. This
      indicates that trial-by-trial variation in neural activity in the P1, N1, P2, and
      N4 components reflects the sequential engagement of low- and high-level parts of
      the auditory pathway for pure tone processing. Our results demonstrate that
      during simple pure tone listening tasks, regions associated with the auditory
      pathway transiently correlate with trial-to-trial variability of the EEG
      amplitude, and they do so on a millisecond timescale with a distinct temporal
      ordering.

PMID- 29191480
TI  - Preterm birth leads to hyper-reactive cognitive control processing and poor white
      matter organization in adulthood.
AB  - Individuals born preterm with very low birth weight (VLBW; birth weight <= 1500
      g) are at high risk for perinatal brain injuries and deviant brain development,
      leading to increased chances of later cognitive, emotional, and behavioral
      problems. Here we investigated the neuronal underpinnings of both reactive and
      proactive cognitive control processes in adults with VLBW. We included 32 adults
      born preterm with VLBW (before 37th week of gestation) and 32 term-born controls
      (birth weight >=10th percentile for gestational age) between 22 and 24 years of
      age that have been followed prospectively since birth. Participants performed a
      well-validated Not-X continuous performance test (CPT) adapted for use in a mixed
      block- and event-related fMRI protocol. BOLD fMRI and DTI data was acquired on a
      3T scanner. Performance on the Not-X CPT was highly similar between groups.
      However, the VLBW group demonstrated hyper-reactive cognitive control processing
      and disrupted white matter organization. The hyper-reactive brain activation
      signature in VLBW adults was associated with lower gestational age, lower fluid
      intelligence score, and anxiety problems. Automated Multi-Atlas Tract Extraction
      (AutoMATE) analyses revealed that this disruption of normal brain function was
      accompanied by poorer white matter organization in the anterior thalamic
      radiation and the cingulum, as reflected in both reduced fractional anisotropy
      and increased mean diffusivity. These findings show that the preterm behavioral
      phenotype is associated with predominantly reactive-, rather than proactive
      cognitive control processing, as well as white matter abnormalities, that may
      underlie common difficulties that many preterm born individuals experience in
      everyday life.

PMID- 29191481
TI  - Surface engineered excipients: I. improved functional properties of fine grade
      microcrystalline cellulose.
AB  - Excipients with good flowability, bulk density as well as compaction properties
      are desired for use in tableting since they play important roles in formulation
      development and processing, including, handling, mixing, feeding and compaction.
      The objective of this paper is to examine the feasibility of using dry coating
      based surface modification of microcrystalline cellulose, Avicel PH-105, to
      produce an engineered fine grade (<30 MUm) excipient that has all three desired
      properties. Using a material sparing high-intensity vibrational mixer, Avciel PH
      105 is dry coated with 1 wt% Aerosil 200, selected due to its relatively higher
      dispersive surface energy and lower particle size amongst other silica choices.
      The results indicated that as expected, the bulk density and flowability are
      significantly improved, while there was an appreciable loss of compaction. To
      minimize the loss of compaction, attributed to decreased surface energy after
      coating, while maintaining improved bulk density and flowability, the effect of
      reduced silica amount was examined. Remarkably, at reduced levels (0.5 wt% to 0.7
      wt%) of Aerosil 200, significant improvements in bulk density and flowability
      were attained with only 9%-12% compaction reduction. The properties of the
      surface-engineered excipients were compared with several other commercially
      available pharmaceutical excipients using two different processibility or regime
      maps; tablet tensile strength versus bulk density or flow function coefficient
      (FFC). The surface engineered excipients exhibited the best overall performance
      establishing a promising pathway to engineer excipients using dry processing
      instead of complex processes such as spray drying.

PMID- 29191482
TI  - Multivariate modeling of diffuse reflectance infrared fourier transform (DRIFT)
      spectra of mixtures with low-content polymorphic impurities with analysis of
      outliers.
AB  - Diffuse Reflectance Fourier Transform Infrared Spectroscopy (DRIFTS)-based
      multivariate models were developed to quantify the content of two polymorphic
      impurities in mixtures with the desired active pharmaceutical ingredient (API)
      form, with the impurities not exceeding 2% wt/wt. In addition, close attention
      was paid to the outlier detection criteria: Q residuals; Hotelling T2; and score
      bi-plot. While reasonably accurate results were obtained for the relatively
      simple calibration models for both forms of the impurity, the predictions for
      "blank" samples (separately verified to be impurity-free) were apparently biased.
      Thus, the model training sets were augmented with spectra from calibration
      mixtures incorporating some of the API from batches used in the prediction. The
      performance of the updated models as assessed by cross-validation was somewhat
      degraded as a result, while predictions against independent batches of API showed
      a decrease in bias indicating robustness had improved. Nevertheless, the Q
      residuals criterion disqualified a large number of prediction samples as outliers
      in contrast to the other two criteria that reported no issues at all. The results
      here demonstrated the effectiveness of DRIFTS for quantifying low concentration
      polymorphic impurities, while simultaneously highlighting the variability issues
      that can be encountered in practice and which need to be understood and managed
      appropriately to ensure the success of any automated or Good Manufacturing
      Practice (GMP) compliant application of multivariate modeling.

PMID- 29191484
TI  - Parameter study of shipping conditions for the ready-to-use application of a 3D
      human hemicornea construct in drug absorption studies.
AB  - In this study, a shipping protocol for our 3D human hemicornea (HC) construct
      should be developed to provide quality-maintaining shipping conditions and to
      allow its ready-to-use application in drug absorption studies. First, the effects
      of single and multiple parameters, such as the type of shipping container,
      storage temperature and CO2 supply, were investigated under controlled laboratory
      conditions by assessing cell viability via MTT dye reaction and epithelial
      barrier properties via transepithelial electrical resistance (TEER) measurements.
      These investigations showed that TEER is more susceptible to shipping parameters
      than cell viability. Furthermore, the results were used to determine the optimal
      shipping conditions and critical values for subsequent overnight, real-time
      shipping experiments. Epithelial barrier properties were then investigated via
      TEER and the permeation of sodium fluorescein for shipped and not shipped HC. The
      results underscore that acceleration forces and changes in position may have a
      great impact on the epithelial barrier of 3D models. Low acceleration values and
      short changes in position caused only minor impairments. However, combined or
      intensive separate effects resulted in considerably low yields after shipping.
      Consequently, barrier-maintaining shipping of 3D in vitro models seems to be
      challenging, as mechanical forces have to be reduced to a minimum.

PMID- 29191483
TI  - Advances in bioresponsive closed-loop drug delivery systems.
AB  - Controlled drug delivery systems are able to improve efficacy and safety of
      therapeutics by optimizing the duration and kinetics of release. Among them,
      closed-loop delivery strategies, also known as self-regulated administration,
      have proven to be a practical tool for homeostatic regulation, by tuning drug
      release as a function of biosignals relevant to physiological and pathological
      processes. A typical example is glucose-responsive insulin delivery system, which
      can mimic the pancreatic beta cells to release insulin with a proper dose at a
      proper time point by responding to plasma glucose levels. Similar self-regulated
      systems are also important in the treatment of other diseases including
      thrombosis and bacterial infection. In this review, we survey the recent advances
      in bioresponsive closed-loop drug delivery systems, including glucose-responsive,
      enzyme-activated, and other biosignal-mediated delivery systems. We also discuss
      the future opportunities and challenges in this field.

PMID- 29191486
TI  - Pulmonary Alveolar Proteinosis: Crazing-Paving Appearance.

PMID- 29191485
TI  - Impact of non-binder ingredients and molecular weight of polymer binders on heat
      assisted twin screw dry granulation.
AB  - Two grades of commercial AFFINISOLTM HPMC HME were used as polymer binders to
      explore the influence of polymer viscosity and concentration on a novel heat
      assisted dry granulation process with a twin screw extruder. Contributions of
      other non-binder ingredients in the formulations were also studied for lactose,
      microcrystalline cellulose and an active pharmaceutical ingredient of caffeine.
      As sensitive indicators of processing conditions that expose the drug to high
      internally generated heat, dehydration of alpha-lactose monohydrate and
      polymorphic transformation of caffeine were monitored by differential scanning
      calorimetry (DSC) and powder X-ray diffraction (XRD). Additionally, any
      decomposition of caffeine was determined by high-performance liquid
      chromatography (HPLC). Granular samples were characterized by particle size,
      circularity, fracture strength and their temperature on the exit of extruder.
      Higher screw speed and lower feed rate were found to help particles agglomerate
      by allowing feed particles a greater opportunity to increase in temperature.
      Lower binder molecular weight and higher binder concentration enable granules to
      build stronger strength and thereby lead to higher particle size. This new twin
      screw dry granulation was demonstrated as offering advantages over conventional
      hot melt granulation by minimizing thermal degradation of the tested ingredients.

PMID- 29191487
TI  - The Physician From Vienna.

PMID- 29191488
TI  - Introduction to Neuroimaging.
AB  - Primary care physicians are often tasked with evaluating neurologic symptoms, and
      imaging plays a critical role in neurologic diagnoses. Neuroradiology routinely
      employs advanced imaging modalities, and hence, determination of the appropriate
      imaging test and interpretation of findings in the clinical context can
      understandably be overwhelming. In this review article, we introduce resources
      that can guide physicians in the selection of neuroimaging tests and summarize
      guidelines on contrast agent administration. Key concepts on imaging techniques
      and terminology are reviewed, as is relevant for the primary care physician. We
      then present an overview of the typical imaging manifestations of brain
      pathologies, including stroke, traumatic injuries, infections, demyelinating and
      neurodegenerative processes, and neoplasms. Spine imaging is often considered for
      the evaluation of degenerative, infectious, or neoplastic etiologies, and the
      typical imaging findings in these scenarios are also summarized.

PMID- 29191489
TI  - Beyond the vicious cycle: The role of innate osteoimmunity, automimicry and tumor
      inherent changes in dictating bone metastasis.
AB  - Bone metastasis is a fatal consequence of a subset of solid malignancies that
      fail to respond to conventional therapies. While a myriad of factors contribute
      to osteotropism and disseminated cell survival and outgrowth in bone, efforts to
      inhibit tumor cell growth in the bone-metastatic niche have largely relied on
      measures that disrupt the bi-directional interactions between bone resident and
      tumor cells. However, the targeting of isolated stromal interactions has proven
      ineffective to date in inhibiting bone-metastatic progression and patient
      mortality. Osteoimmune regulation is now emerging as a critical determinant of
      metastatic growth in the bone microenvironment. While this has highlighted the
      importance of innate immune populations in dictating the temporal development of
      overt bone metastases, the osteoimmunological processes that underpin tumor cell
      progression in bone remain severely underexplored. Along with tumor-intrinsic
      alterations that occur specifically within the bone microenvironment, innate
      osteoimmunological crosstalk poses an exciting area of future discovery and
      therapeutic development. Here we review current knowledge of the unique exchange
      that occurs between bone resident cells, innate immune populations and tumor
      cells that leads to the establishment of a tumor-permissive milieu.

PMID- 29191490
TI  - Prognosticating Clinical Prediction Scores Without Clinical Gestalt for Patients
      With Chest Pain in the Emergency Department.
AB  - BACKGROUND: Assessment of patients with chest pain is a regular challenge in the
      emergency department (ED). Recent guidelines recommended quantitative assessment
      of ischemic risk by means of risk scores. OBJECTIVE: Our aim was to assess the
      performance of Thrombosis in Myocardial Infarction (TIMI); Global Registry of
      Acute Coronary Events (GRACE); history, electrocardiogram, age, risk factors, and
      troponin (HEART) scores; and the North America Chest Pain Rule (NACPR) without
      components of clinical gestalt in predicting 30-day major adverse cardiac events
      (MACE). METHODS: We performed a prospective cohort study in adult patients who
      attended the ED with undifferentiated chest pain. Clinical prediction rules were
      applied and calculated. The clinical prediction rules were modified from the
      original ones, excluding components requiring judgment by clinical gestalt. The
      primary outcome was MACE. Performance of the tests were evaluated by receive
      operating characteristic curves and the area under curves (AUC). RESULTS: There
      were 1081 patients included in the study. Thirty-day MACE occurred in 164 (15.2%)
      patients. The AUC of the GRACE score was 0.756, which was inferior to the TIMI
      score (AUC 0.809) and the HEART score (AUC 0.845). A TIMI score >= 1 had a
      sensitivity of 97% and a specificity of 45.7%. A GRACE score >= 50 had a
      sensitivity of 99.4% and a specificity of 7.5%. A HEART score >= 1 had a
      sensitivity of 98.8% and a specificity of 11.7%. The NACPR had a sensitivity of
      93.3% and a specificity of 51.5%. CONCLUSIONS: Without clinical gestalt, the
      modified HEART score had the best discriminative capacity in predicting 30-day
      MACE.

PMID- 29191491
TI  - A nested-PCR strategy for molecular diagnosis of mollicutes in uncultured
      biological samples from cows with vulvovaginitis.
AB  - Bacteria classified in Mycoplasma (M. bovis and M. bovigenitalium) and Ureaplasma
      (U. diversum) genera are associated with granular vulvovaginitis that affect
      heifers and cows at reproductive age. The traditional means for detection and
      speciation of mollicutes from clinical samples have been culture and serology.
      However, challenges experienced with these laboratory methods have hampered
      assessment of their impact in pathogenesis and epidemiology in cattle worldwide.
      The aim of this study was to develop a PCR strategy to detect and primarily
      discriminate between the main species of mollicutes associated with reproductive
      disorders of cattle in uncultured clinical samples. In order to amplify the 16S
      23S rRNA internal transcribed spacer region of the genome, a consensual and
      species-specific nested-PCR assay was developed to identify and discriminate
      between main species of mollicutes. In addition, 31 vaginal swab samples from
      dairy and beef affected cows were investigated. This nested-PCR strategy was
      successfully employed in the diagnosis of single and mixed mollicute infections
      of diseased cows from cattle herds from Brazil. The developed system enabled the
      rapid and unambiguous identification of the main mollicute species known to be
      associated with this cattle reproductive disorder through differential
      amplification of partial fragments of the ITS region of mollicute genomes. The
      development of rapid and sensitive tools for mollicute detection and
      discrimination without the need for previous cultures or sequencing of PCR
      products is a high priority for accurate diagnosis in animal health. Therefore,
      the PCR strategy described herein may be helpful for diagnosis of this class of
      bacteria in genital swabs submitted to veterinary diagnostic laboratories, not
      demanding expertise in mycoplasma culture and identification.

PMID- 29191492
TI  - Initial clinical assessment of "center-specific" automated treatment plans for
      low-dose-rate prostate brachytherapy.
AB  - PURPOSE: To report results of an initial pilot study assessing iodine-125
      prostate implant treatment plans created automatically by a new seed-placement
      method. METHODS AND MATERIALS: A novel mixed-integer linear programming method
      incorporating spatial constraints on seed locations in addition to standard dose
      volume constraints was used to place seeds. The approach, described in detail
      elsewhere, was used to create treatment plans fully automatically on a
      retrospective basis for 20 patients having a wide range of prostate sizes and
      shapes. Corresponding manual plans used for patient treatment at a single
      institution were combined with the automated plans, and all 40 plans were
      anonymized, randomized, and independently evaluated by five clinicians using a
      common scoring tool. Numerical and clinical features of the plans were extracted
      for comparison purposes. RESULTS: A full 51% of the automated plans were deemed
      clinically acceptable without any modification by the five practitioners
      collectively versus 90% of the manual plans. Automated plan seed distributions
      were for the most part not substantially different from those for the manual
      plans. Two observed shortcomings of the automated plans were seed strands not
      intersecting the prostate and strands extending into the bladder. Both are
      amenable to remediation by adjusting existing spatial constraints. CONCLUSIONS:
      After spatial and dose-volume constraints are set, the mixed-integer linear
      programming method is capable of creating prostate implant treatment plans fully
      automatically, with clinical acceptability sufficient to warrant further
      investigation. These plans, intended to be reviewed and refined as necessary by
      an expert planner, have the potential to both save planner time and enhance
      treatment plan consistency.

PMID- 29191493
TI  - Effects of melatonin supplementation on blood lipid concentrations: A systematic
      review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND & AIMS: Melatonin supplementation may be associated with blood lipids
      improvement; however, the current evidence from randomized controlled trials
      (RCTs) is inconsistent. The present study aimed to systematically review and
      analyze RCTs assessing the effects of melatonin supplementation on blood lipids.
      METHODS: A comprehensive literature search in several database was performed up
      to January 2017. Quantitative data synthesis was performed using a fixed or
      random-effects model, with weight mean difference (WMD) and 95% confidence
      intervals (CI). Standard methods were used for assessment of heterogeneity, meta
      regression, sensitivity analysis and publication bias. RESULTS: A total of 8 RCTs
      were eligible. Meta-analysis suggested a significant association between
      melatonin supplementation and a reduction in triglycerides (WMD: -31.54 mg/dL,
      95% CI: -50.71, -12.38, p = 0.001), and total cholesterol levels (WMD: -18.48
      mg/dL, 95% CI: -35.33, -1.63, p = 0.032), while no significant effect on LDL-C
      (WMD: -2.37 mg/dL, 95% CI: -11.61, -6.86, p = 0.615) and HDL-C (WMD: 1.28 mg/dL,
      95% CI: -0.66, 3.23, p = 0.197) was found. In sub-group analysis, a significant
      decrease in triglycerides was found at doses >=8 mg/d and when trials last >=8
      weeks. In addition, a significant decrease of total cholesterol was found at
      doses >=8 mg/d and when total cholesterol baseline levels were >=200 mg/dL.
      CONCLUSIONS: Melatonin supplementation has significant effects on triglycerides
      and total cholesterol levels, which was more evident in higher dose and longer
      duration and also in a higher concentration of cholesterol levels. Further
      studies are required to determine the benefits of melatonin on lipid profile.

PMID- 29191494
TI  - Low protein intake, muscle strength and physical performance in the very old: The
      Newcastle 85+ Study.
AB  - BACKGROUND: Low protein intake has been linked to reduced muscle strength and
      physical performance in older adults but little is known about how it may affect
      muscle health and subsequent functional decline in the very old (aged 85+), who
      are at enhanced risk of malnutrition and loss of muscle mass and strength. AIMS:
      To investigate the associations between low protein intake, defined as the intake
      of <1 g protein/kg adjusted body weight/day (<1 g/kg aBW/d) and decline in muscle
      strength and physical performance in the very old. METHODS: The analytic sample
      consisted of 722 community-dwelling participants (60% women) from the Newcastle
      85+ Study who had protein intake at baseline. Participants were followed-up for
      change in grip strength (GS) and Timed Up-and-Go (TUG) test over 5 years
      (baseline, 18, 36, and 60 months). We used mixed models to determine the effects
      of low protein intake on muscle strength and physical performance in all
      participants, and also stratified by sex. RESULTS: At baseline, 390 (54%)
      participants (261 women, p < 0.001) reported low protein intake, and these
      differed from participants with good intake (>=1 g/kg aBW/d) on several measures
      of health and function. In the model adjusted for protein intake, consuming <1
      g/kg aBW/d of protein was associated with a 1.62 kg lower GS (p = 0.008) in all
      participants, and especially in women (beta (SE) = -0.83 (0.41), p = 0.05) after
      adjusting for key baseline covariates (anthropometry, multimorbidity, arthritis
      in hands, cognitive status and physical activity). The rate of decline in GS over
      5 years was not associated with protein intake. Women, but not men, with low
      protein intake had worse baseline TUG (beta (SE) = 0.04 (0.02), p = 0.03)
      compared with those with good protein intake in the fully adjusted model, but the
      rate of decline in TUG was not affected by daily protein status. CONCLUSIONS:
      Intake of <1 g protein/kg aBW/d may negatively affect muscle strength and
      physical performance in late life, especially in older women, independently of
      important covariates. More research is needed in the very old to define the
      optimal protein intake for maintenance of muscle health and function.

PMID- 29191495
TI  - Atopic disorders in CHARGE syndrome: A retrospective study and literature review.
AB  - BACKGROUND: Atopic disorders have been reported in CHARGE syndrome, but the
      prevalence and underlying mechanisms are not known. METHODS: We performed a
      retrospective study of atopic disorders in 23 individuals with CHARGE syndrome,
      and reviewed other published reports of atopic disorders in CHARGE syndrome. We
      assayed for enrichment of atopic disorders in CHARGE syndrome based on gender and
      presence of a CHD7 pathogenic variant. RESULTS: In our cohort, 65% (15/23) of
      individuals with CHARGE syndrome were found to have a pathogenic CHD7 variant.
      Overall, 65% (15/23) of individuals with CHARGE had atopic disorders. Among the
      23 individuals with CHARGE, 22% (5/23) had food allergy, 26% (6/23) exhibited
      drug allergy, 22% (5/23) had contact allergy, 9% (2/23) had allergic rhinitis,
      and 22% (5/23) had asthma. In our cohort, the proportion of males to females with
      CHARGE and atopic disorders was 11:4 (P < 0.01), and there was no significant
      difference between atopic disorders in individuals with CHD7 pathogenic variants
      and those without CHD7 pathogenic variants (P > 0.05). CONCLUSION: In our cohort
      of 23 individuals with CHARGE syndrome, 15 (65%) exhibited atopic disorders, with
      a slight male predominance.

PMID- 29191496
TI  - A higher rare CNV burden in the genetic background potentially contributes to
      intellectual disability phenotypes in 22q11.2 deletion syndrome.
AB  - The 22q11.2 deletion syndrome (22q11DS), the most common survivable human genetic
      deletion disorder, is caused by a hemizygous deletion of 30-40 contiguous genes
      on chromosome 22, many of which have not been well characterized. Clinical
      features seen in patients with this deletion, including intellectual disability,
      are not completely penetrant and vary in severity between patients, suggesting
      the involvement of variants elsewhere in the genome in the manifestation of the
      phenotype. Given that it is a relatively rare disorder (1/2000-6000 in humans),
      limited research has shed light into the contribution of these second-site
      variants to the developmental pathogenesis that underlies 22q11DS. As CNVs
      throughout the genome might constitute such a genetic risk factor for variability
      in the 22q11DS phenotypes such as intellectual disability, we sought to determine
      if the overall burden of rare CNVs in the genetic background influenced the
      phenotypic variability. We analyzed CNV and clinical data from 66 individuals
      with 22q11DS, and found that 77% (51/66) of individuals with the 22q11DS also
      carry additional rare CNVs (<0.1% frequency). We observed several trends between
      CNV burden and phenotype, including that the burden of large rare CNVs (>200 Kb
      in size) was significantly higher in 22q11DS individuals with intellectual
      disability than with normal IQ. Our analysis shows that rare CNVs may contribute
      to intellectual disability 22q11DS, and further analysis on larger 22q11DS
      cohorts should be performed to confirm this correlation.

PMID- 29191497
TI  - Recontacting in light of new genetic diagnostic techniques for patients with
      intellectual disability: Feasibility and parental perspectives.
AB  - A higher diagnostic yield from new diagnostic techniques makes re-evaluation in
      patients with intellectual disability without a causal diagnosis valuable, and is
      currently only performed after new referral. Active recontacting might serve a
      larger group of patients. We aimed to evaluate parental perspectives regarding
      recontacting and its feasibility in clinical genetic practice. A recontacting
      pilot was performed in two cohorts of children with intellectual disability. In
      cohort A, parents were recontacted by phone and in cohort B by letter, to invite
      them for a re-evaluation due to the new technologies (array CGH and exome
      sequencing, respectively). Parental opinions, preferences and experiences with
      recontacting were assessed by a self-administered questionnaire, and the
      feasibility of this pilot was evaluated. 47 of 114 questionnaires were returned.
      In total, 87% of the parents believed that all parents should be recontacted in
      light of new insights, 17% experienced an (positive or negative) emotional
      reaction. In cohort A, approached by phone, 36% made a new appointment for re
      evaluation, and in cohort B, approached by letter, 4% did. Most parents have
      positive opinions on recontacting. Recontacting might evoke emotional responses
      that may need attention. Recontacting is feasible but time-consuming and a large
      additional responsibility for clinical geneticists.

PMID- 29191498
TI  - A report of three families with FBN1-related acromelic dysplasias and review of
      literature for genotype-phenotype correlation in geleophysic dysplasia.
AB  - Acromelic dysplasia is a heterogeneous group of rare skeletal dysplasias
      characterized by distal limb shortening. Weill-Marchesani syndrome (WMS),
      Geleophysic dysplasia (GD) and Acromicric dysplasia (AD) are clinically distinct
      entities within this group of disorders and are characterized by short stature,
      short hands, stiff joints, skin thickening, facial anomalies, normal intelligence
      and skeletal abnormalities. Mutations of the Fibrillin-1 (FBN1) gene have been
      reported to cause AD, GD and related phenotypes. We reported three families with
      acromelic short stature. FBN1 analysis showed that all affected individuals carry
      a heterozygous missense mutation c.5284G > A (p.Gly1762Ser) in exon 42 of the
      FBN1 gene. This mutation was previously reported to be associated with GD. We
      reviewed the literature and compared the clinical features of the patients with
      FBN1 mutations to those with A Distintegrin And Metalloproteinase with
      Thrombospondin repeats-like 2 gene (ADAMTSL2) mutations. We found that tip-toeing
      gait, long flat philtrum and thin upper upper lip were more consistently found in
      GD patients with ADAMTSL2 mutations than in those with FBN1 mutations. The
      results have shed some light on the phenotype-genotype correlation in this group
      of skeletal disorders. A large scale study involving multidisciplinary
      collaboration would be needed to consolidate our findings.

PMID- 29191499
TI  - Animal waste and waste animal by-products generated along the livestock breeding
      and meat food chain.

PMID- 29191500
TI  - 3T non-injected phase-contrast MRI sequences for the mapping of the external
      carotid branches: In vivo radio-anatomical pilot study for feasibility analysis.
AB  - An essential stage in head and neck microsurgical reconstruction is the choice of
      recipient vessels. To make relevant choices, surgeons must rely on accurate
      imaging techniques. The objective of the study was to examine the feasibility of
      Phase-Contrast sequences to conduct the pre-operative tests without injection and
      provide precise radio-anatomical data over the entire vessel region. The
      challenges were the large velocity range, the lack of contrast, and the large
      spatial resolution needed to image vessels below 5 mm in diameter. Thirty-one
      healthy volunteers were included in an MRI prospective study. The anatomical and
      morphometrical characteristics of the collaterals of the external carotid artery
      were determined associating 3D PCA and 2D Cine MRI-PC sequences (average
      protocole duration time of 49 min +/- 4 min). The average diameter was measured
      to be 2.1 +/- 1.4 mm for the superior thyroid artery, 2.2 +/- 1.1 mm for the
      lingual artery, 2.7 +/- 1.6 mm for the facial artery, 2.6 +/- 1.4 mm for the
      internal maxillary artery, and 2 +/- 1.4 mm for the superficial temporal artery.
      With a vessel identification success rate of 98%, the study showed for the first
      time that Phase Contrast MRI allowed non-invasive and non-operator dependent
      anatomical analyses of small caliber vessels without the use of agent contrast.
      It also proved that the designed sequences could be used on patients and provided
      valuable pre-operative information for head and neck surgery.

PMID- 29191501
TI  - Immunoprecipitation high performance liquid chromatographic analysis of healing
      process in chronic suppurative osteomyelitis of the jaw.
AB  - PURPOSE: Chronic suppurative osteomyelitis (CSO) of the jaw is one of the most
      difficult infectious diseases to manage, because it causes progressive bony
      destruction and is associated with bacterial inhabitation of the sequestra. A
      combination of antibiotic therapy and surgical debridement is often used to treat
      CSO. Nevertheless, various systemic conditions can lead to life-threatening
      complications. METHODS: The present study aimed to explore the wound healing
      progress in 16 cases of CSO through protein expression analysis of postoperative
      exudates (POE) that were collected 6 h, 1 day, and 2 days after saucerization
      and/or decortication. A bony lesion was removed during surgery and then examined
      pathologically, and the CSO POE was examined by immunoprecipitation thus high
      performance chromatography (IP-HPLC). The POE at 6 h was used as a comparative
      control. RESULTS: Histologically the CSO lesion showed a necrotic granulomatous
      lesion heavily infiltrated with polymorphonuclear leukocytes, macrophages, and
      plasma cells, admixed with multiple sequestra inhabited by bacterial colonies.
      The IP-HPLC analysis displayed a slight increase in innate immunity-related
      proteins, i.e., NFkB, TNFalpha, IL-1, IL-6, IL-28, and LL-37, but a gradual
      decrease of bacteria-related inflammatory proteins, i.e., IL-8, IL-12, CD31,
      CD68, and lysozyme. The angiogenesis-related proteins, i.e., VEGF-A and VEGF-C,
      were slightly decreased but TGF-beta1 and bFGF were markedly increased on day 2.
      The osteogenesis-related proteins, i.e., OPG and ALP, were slightly increased,
      while the osteoclastogenesis-related protein, RANKL was slightly decreased
      compared to the control. CONCLUSION: These findings indicate that the infected
      CSO undergoes a rapid wound healing process with active osteogenesis and a
      gradual decrease in bacteria-related inflammation, predicting a favorable
      prognosis after surgery. Moreover, IP-HPLC can be useful in monitoring the POE
      and wound healing processes during the postoperative period.

PMID- 29191502
TI  - Synthesis, in vitro and in silico evaluation of novel trans-stilbene analogues as
      potential COX-2 inhibitors.
AB  - 25 new trans-stilbene and trans-stilbazole derivatives were investigated using in
      vitro and in silico techniques. The selectivity and potency of the compounds were
      assessed using commercial ELISA test. The obtained results were incorporated into
      2D QSAR assay. The most promising compound 4-nitro-3',4',5'-trihydroxy-trans
      stilbene (N1) was synthetized and its potency and selectivity were confirmed. N1
      was classified as preferential COX-2 inhibitor. Its ability to inhibit COX-2 in
      MCF-7 cell line was established and its cytotoxicity by MTT test was assessed.
      The compound was more cytotoxic than celecoxib within studied concentration
      range. Finally, the investigated trans-stilbene was docked into COX-1 and COX-2
      active sites using "CDOCKER" protocol.

PMID- 29191504
TI  - Predictors of In-Hospital Mortality in Patients With ST-Segment Elevation
      Myocardial Infarction Complicated With Cardiogenic Shock.
AB  - BACKGROUND: ST-segment elevation myocardial infarction (STEMI) complicated with
      cardiogenic shock (CS) remains as an unresolved condition causing high morbidity
      and mortality despite advances in medical treatment and coronary intervention
      procedures. In the current study, we evaluated the predictors of in-hospital
      mortality of STEMI complicated with CS. METHODS: In this retrospective study, we
      evaluated the predictive value of baseline characteristics, angiographic,
      echocardiographic and laboratory parameters on in-hospital mortality of 319
      patients with STEMI complicated with CS who were treated with primary
      percutaneous coronary intervention. Patients were divided into two groups
      consisting of survivors and non-survivors during their index hospitalisation
      period. RESULTS: The mortality rate was found to be 61.3% in the study
      population. At multivariate analysis after adjustment for the parameters detected
      in univariate analysis, chronic renal failure, Thrombolysis In Myocardial
      Infarction (TIMI) post percutaneous coronary intervention (PCI) <=2, plasma
      glucose and lactate level, blood urea nitrogen level, Tricuspid Annular Plane
      Systolic Excursion (TAPSE) and ejection fraction were independent predictors of
      in-hospital mortality. CONCLUSIONS: Apart from haemodynamic deterioration,
      angiographic, echocardiographic and laboratory parameters have an impact on in
      hospital mortality in patients with STEMI complicated with CS.

PMID- 29191503
TI  - Management of Adults With Congenital Heart Disease and Pulmonary Arterial
      Hypertension in the UK: Survey of Current Practice, Unmet Needs and Expert
      Commentary.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a well-recognised
      complication of adult congenital heart disease (CHD). However, management is not
      currently standardised between centres and specific guidelines are lacking. In
      order to identify and understand the unmet needs related to PAH associated with
      CHD (PAH-CHD), a survey of physicians was performed. METHODS: An electronic
      survey was sent to two physician groups: (1) cardiologists registered in a UK
      cardiology directory; (2) specialist pulmonary hypertension (PH) physicians known
      to manage patients with adult PAH-CHD. The questions related to referral
      pathways, screening, therapy and palliative care. RESULTS: 821 surveys were
      distributed and 106 were returned. Respondents included a broad mix of specialist
      physicians with many patients along with general cardiologists managing only a
      small number of PAH-CHD patients. Although 97% of respondents have access to a
      specialist PH centre, patients are still being managed in non-specialist
      settings. Shared care arrangements are widespread but only 41% have formal shared
      care protocols. Palliative care services are limited and general cardiologists
      rarely perform 6-minute walk tests (6MWT) or quality of life assessments. People
      with PAH-CHD are often undertreated, with 39% of respondents reporting that fewer
      than 25% of these patients were receiving PAH-specific therapies. CONCLUSIONS:
      The survey revealed gaps and inconsistencies in the management of patients with
      PAH-CHD therefore patient-specific guidance is needed for many of these aspects.

PMID- 29191505
TI  - Predictors of Frequent Readmissions in Patients With Heart Failure.
AB  - BACKGROUND: Patients with heart failure (HF) have a high incidence of hospital
      readmissions. However risk models that explore predictors of a single readmission
      may be less useful at identifying the patients with frequent readmissions who
      contribute to a disproportionately large proportion of morbidity and health care
      costs. METHODS: A total of 6252 patients enrolled in the Management of Cardiac
      Failure Program (MACARF) in Northern Sydney Area Hospitals between 1998 and 2015
      were randomly divided into derivation and validation cohorts to create and test a
      risk model for predictors of >=2 readmissions or death within 1year of initial
      hospitalisation for HF. RESULTS: Multivariate predictors of frequent (>=2)
      readmissions or death were a history of ischaemic heart disease and chronic
      kidney disease, being unmarried, having anaemia, low serum albumin, elevated
      creatinine, prolonged hospital stay (>7 days), and not receiving beta blockers on
      discharge. Event rates increased with a higher risk score (p<0.001) and the
      prediction was similar in the validation and derivation cohorts (p=0.588). The C
      statistic was 0.65. CONCLUSIONS: Our risk score may assist in focussing health
      care resources and interventions by identifying the subset of HF patients at
      increased risk for a disproportionately high burden of disease.

PMID- 29191506
TI  - A Practical Guide for Fractional Flow Reserve Guided Revascularisation.
AB  - The presence and extent of myocardial ischaemia is a major determinant of
      prognosis and benefit from revascularisation in patients with stable coronary
      artery disease. Fractional Flow Reserve (FFR) is accepted as the reference
      standard for invasive assessment of ischaemia. Its ability to detect lesion
      specific ischaemia makes it a useful test in a wide range of patient and lesion
      subsets, with FFR guided intervention improving clinical outcomes and reducing
      health care costs compared to assessment with coronary angiography alone. This
      article will review the basic principles in FFR, practical tips in FFR guided
      revascularisation and the role of emerging non-hyperaemic indices of ischaemia.

PMID- 29191508
TI  - In vivo performance of freeze-dried decellularized pulmonary heart valve allo-
      and xenografts orthotopically implanted into juvenile sheep.
AB  - : The decellularization of biological tissues decreases immunogenicity, allows
      repopulation with cells, and may lead to improved long-term performance after
      implantation. Freeze drying these tissues would ensure off-the-shelf
      availability, save storage costs, and facilitates easy transport. This study
      evaluates the in vivo performance of freeze-dried decellularized heart valves in
      juvenile sheep. TritonX-100 and sodium dodecylsulfate decellularized ovine and
      porcine pulmonary valves (PV) were freeze-dried in a lyoprotectant sucrose
      solution. After rehydration for 24 h, valves were implanted into the PV position
      in sheep as allografts (fdOPV) and xenografts (fdPPV), while fresh dezellularized
      ovine grafts (frOPV) were implanted as controls. Functional assessment was
      performed by transesophageal echocardiography at implantation and at explantation
      six months later. Explanted grafts were analysed histologically to assess the
      matrix, and immunofluorescence stains were used to identify the repopulating
      cells. Although the graft diameters and orifice areas increased, good function
      was maintained, except for one insufficient, strongly deteriorated frOPV. Cells
      which were positive for either endothelial or interstitial markers were found in
      all grafts. In fdPPV, immune-reactive cells were also found. Our findings suggest
      that freeze-drying does not alter the early hemodynamic performance and
      repopulation potential of decellularized grafts in vivo, even in the challenging
      xenogeneic situation. Despite evidence of an immunological reaction for the
      xenogenic valves, good early functionalities were achieved. STATEMENT OF
      SIGNIFICANCE: Decellularized allogeneic heart valves show excellent results as
      evident from large animal experiments and clinical trials. However, a long-term
      storing method is needed for an optimal use of this limited resource in the
      clinical setting, where an optimized matching of graft and recipient is
      requested. As demonstrated in this study, freeze-dried and freshly decellularized
      grafts reveal equally good results after implantation in the juvenile sheep
      concerning function and repopulation with recipients' cells. Thus, freeze-drying
      arises as a promising method to extend the shelf-life of valvular grafts compared
      to those stored in antibiotic-solution as currently practised.

PMID- 29191507
TI  - Viscoelastic properties of human pancreatic tumors and in vitro constructs to
      mimic mechanical properties.
AB  - : Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large
      part due to a protective fibrotic barrier generated by tumor-associated stromal
      (TAS) cells. This barrier is thought to promote cancer cell survival and
      confounds attempts to develop effective therapies. We present a 3D in vitro
      system that replicates the mechanical properties of the PDAC microenvironment,
      representing an invaluable tool for understanding the biology of the disease.
      Mesoscale indentation quantified viscoelastic metrics of resected malignant
      tumors, inflamed chronic pancreatitis regions, and histologically normal tissue.
      Both pancreatitis (2.15 +/- 0.41 kPa, Mean +/- SD) and tumors (5.46 +/- 3.18 kPa)
      exhibit higher Steady-State Modulus (SSM) than normal tissue (1.06 +/- 0.25 kPa;
      p < .005). The average viscosity of pancreatitis samples (63.2 +/- 26.7 kPa.s) is
      significantly lower than that of both normal tissue (252 +/- 134 kPa.s) and
      tumors (349 +/- 222 kPa.s; p < .005). To mimic this remodeling behavior, PDAC and
      TAS cells were isolated from human PDAC tumors. Conditioned medium from PDAC
      cells was used to culture TAS-embedded collagen hydrogels. After 7 days, TAS
      embedded gels in control medium reached SSM (1.45 +/- 0.12 kPa) near normal
      pancreas, while gels maintained with conditioned medium achieved higher SSM (3.38
      +/- 0.146 kPa) consistent with tumors. Taken together, we have demonstrated an in
      vitro system that recapitulates in vivo stiffening of PDAC tumors. In addition,
      our quantification of viscoelastic properties suggests that elastography
      algorithms incorporating viscosity may be able to more accurately distinguish
      between pancreatic cancer and pancreatitis. STATEMENT OF SIGNIFICANCE:
      Understanding tumor-stroma crosstalk in pancreatic ductal adenocarcinoma (PDAC)
      is challenged by a lack of stroma-mimicking model systems. To design appropriate
      models, pancreatic tissue must be characterized with a method capable of
      evaluating in vitro models as well. Our indentation-based characterization tool
      quantified the distinct viscoelastic signatures of inflamed resections from
      pancreatitis, tumors from PDAC, and otherwise normal tissue to inform development
      of mechanically appropriate engineered tissues and scaffolds. We also made
      progress toward a 3D in vitro system that recapitulates mechanical properties of
      tumors. Our in vitro model of stromal cells in collagen and complementary
      characterization system can be used to investigate mechanisms of cancer-stroma
      crosstalk in PDAC and to propose and test innovative therapies.

PMID- 29191509
TI  - Cavitation nucleation in gelatin: Experiment and mechanism.
AB  - : Dynamic cavitation in soft materials is becoming increasingly relevant due to
      emerging medical implications such as the potential of cavitation-induced brain
      injury or cavitation created by therapeutic medical devices. However, the current
      understanding of dynamic cavitation in soft materials is still very limited,
      mainly due to lack of robust experimental techniques. To experimentally
      characterize cavitation nucleation under dynamic loading, we utilize a recently
      developed experimental instrument, the integrated drop tower system. This
      technique allows quantitative measurements of the critical acceleration (acr)
      that corresponds to cavitation nucleation while concurrently visualizing time
      evolution of cavitation. Our experimental results reveal that acr increases with
      increasing concentration of gelatin in pure water. Interestingly, we have
      observed the distinctive transition from a sharp increase (pure water to 1%
      gelatin) to a much slower rate of increase (~10* slower) between 1% and 7.5%
      gelatin. Theoretical cavitation criterion predicts the general trend of
      increasing acr, but fails to explain the transition rates. As a likely mechanism,
      we consider concentration-dependent material properties and non-spherical
      cavitation nucleation sites, represented by pre-existing bubbles in gels, due to
      possible interplay between gelatin molecules and nucleation sites. This analysis
      shows that cavitation nucleation is very sensitive to the initial configuration
      of a bubble, i.e., a non-spherical bubble can significantly increase acr. This
      conclusion matches well with the experimentally observed liquid-to-gel transition
      in the critical acceleration for cavitation nucleation. STATEMENT OF
      SIGNIFICANCE: From a medical standpoint, understanding dynamic cavitation within
      soft materials, i.e., tissues, is important as there are both potential injury
      implications (blast-induced cavitation within the brain) as well as treatments
      utilizing the phenomena (lithotripsy). In this regard, the main results of the
      present work are (1) quantitative characterization of cavitation nucleation in
      gelatin samples as a function of gel concentration utilizing well-controlled
      mechanical impacts and (2) mechanistic understanding of complex coupling between
      cavitation and liquid-/solid-like material properties of gel. The new
      capabilities of testing soft gels, which can be tuned to mimic material
      properties of target organs, at high loading rate conditions and accurately
      predicting their cavitation behavior are an important step towards developing
      reliable cavitation criteria in the scope of their biomedical applications.

PMID- 29191510
TI  - Transplantation of human amnion prevents recurring adhesions and ameliorates
      fibrosis in a rat model of sciatic nerve scarring.
AB  - : Peripheral nerve fibrosis and painful adhesions are common, recurring
      pathological sequelae following injury. In this study, vital human amnion (hAM),
      an increasingly interesting biomaterial for regenerative medicine, was
      investigated as a novel therapy. hAM was first analyzed in vitro regarding its
      anti-adhesive characteristics. Then, the reflected region of hAM which was
      identified as more suitable, was transplanted into female Sprague Dawley rats
      with recurring sciatic nerve scarring (n = 24) and compared with untreated
      controls (n = 30) at one, four and twelve weeks. Immune response and fibrosis
      were investigated by (immuno)histochemical analysis. Nerve structure was examined
      and function determined using electrophysiology and gait analysis. Here we
      identified strongly reduced adhesions in the hAM-treated rats, displaying a
      significant difference at four weeks post transplantation compared to untreated
      controls (p = .0052). This correlated with the in vitro cell attachment test on
      hAM explants, which demonstrated a distinctly limited ability of fibroblasts to
      adhere to amniotic epithelial cells. Upon hAM transplantation, significantly less
      intraneural fibrosis was identified at the later time points. Moreover, hAM
      treated rats exhibited a significantly higher sciatic functional index (SFI)
      after four weeks compared to controls (p < .05), which indicated a potentially
      pro-regenerative effect of hAM. As a possible explanation, an impact of hAM on
      the endogenous immune response, including T cell and macrophage subsets, was
      indicated. We conclude that hAM is strongly effective against recurring nerve
      scarring and induces an anti-fibrotic and pro-regenerative effect, making it
      highly promising for treating adhesion-related disorders. STATEMENT OF
      SIGNIFICANCE: Abnormal fibrotic bonding of tissues, frequently involving
      peripheral nerves, affects millions of people worldwide. These so-called
      adhesions usually cause severe pain and drastically reduce quality of life. To
      date, no adequate treatment exists and none is routinely used in the clinical
      practice. In this study, vital human amnion, the innermost of the fetal
      membranes, was transplanted in a rat model of peripheral nerve scarring and
      recurring adhesions as novel therapeutic approach. Amniotic cells have already
      demonstrated to feature stem-cell like properties and produce pro-regenerative
      factors, which makes the amnion an increasingly promising biomaterial for
      regenerative medicine. We identified that its transplantation was very effective
      against peripheral nerve scarring and distinctly reduced recurring adhesions.
      Moreover, we identified a pro-regenerative effect. This study showed that the
      amnion is a highly promising novel therapeutic approach for adhesion-related
      disorders.

PMID- 29191511
TI  - The Role of Inhibition in Avoiding Distraction by Salient Stimuli.
AB  - Researchers have long debated whether salient stimuli can involuntarily 'capture'
      visual attention. We review here evidence for a recently discovered inhibitory
      mechanism that may help to resolve this debate. This evidence suggests that
      salient stimuli naturally attempt to capture attention, but capture can be
      avoided if the salient stimulus is suppressed before it captures attention.
      Importantly, the suppression process can be more or less effective as a result of
      changing task demands or lapses in cognitive control. Converging evidence for the
      existence of this suppression mechanism comes from multiple sources, including
      psychophysics, eye-tracking, and event-related potentials (ERPs). We conclude
      that the evidence for suppression is strong, but future research will need to
      explore the nature and limits of this mechanism.

PMID- 29191512
TI  - A unique respiratory adaptation in Drosophila independent of supercomplex
      formation.
AB  - Large assemblies of respiratory chain complexes, known as supercomplexes, are
      present in the mitochondrial membrane in mammals and yeast, as well as in some
      bacterial membranes. The formation of supercomplexes is thought to contribute to
      efficient electron transfer, stabilization of each enzyme complex, and inhibition
      of reactive oxygen species (ROS) generation. In this study, mitochondria from
      various organisms were solubilized with digitonin, and then the solubilized
      complexes were separated by blue native PAGE (BN-PAGE). The results revealed a
      supercomplex consisting of complexes I, III, and IV in mitochondria from bovine
      and porcine heart, and a supercomplex consisting primarily of complexes I and III
      in mitochondria from mouse heart and liver. However, supercomplexes were barely
      detectable in Drosophila flight-muscle mitochondria, and only dimeric complex V
      was present. Drosophila mitochondria exhibited the highest rates of oxygen
      consumption and NADH oxidation, and the concentrations of the electron carriers,
      cytochrome c and quinone were higher than in other species. Respiratory chain
      complexes were tightly packed in the mitochondrial membrane containing abundant
      phosphatidylethanolamine with the fatty acid palmitoleic acid (C16:1), which is
      relatively high oxidation-resistant as compared to poly-unsaturated fatty acid.
      These properties presumably allow efficient electron transfer in Drosophila.
      These findings reveal the existence of a new mechanism of biological adaptation
      independent of supercomplex formation.

PMID- 29191513
TI  - International consensus on definition and criteria of borderline resectable
      pancreatic ductal adenocarcinoma 2017.
AB  - This statement was developed to promote international consensus on the definition
      of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) which was
      adopted by the National Comprehensive Cancer Network (NCCN) in 2006, but which
      has changed yearly and become more complicated. Based on a symposium held during
      the 20th meeting of the International Association of Pancreatology (IAP) in
      Sendai, Japan, in 2016, the presenters sought consensus on issues related to BR
      PDAC. We defined patients with BR-PDAC according to the three distinct
      dimensions: anatomical (A), biological (B), and conditional (C). Anatomic factors
      include tumor contact with the superior mesenteric artery and/or celiac artery of
      less than 180 degrees  without showing stenosis or deformity, tumor contact with
      the common hepatic artery without showing tumor contact with the proper hepatic
      artery and/or celiac artery, and tumor contact with the superior mesenteric vein
      and/or portal vein including bilateral narrowing or occlusion without extending
      beyond the inferior border of the duodenum. Biological factors include
      potentially resectable disease based on anatomic criteria but with clinical
      findings suspicious for (but unproven) distant metastases or regional lymph nodes
      metastases diagnosed by biopsy or positron emission tomography-computed
      tomography. This also includes a serum carbohydrate antigen (CA) 19-9 level more
      than 500 units/ml. Conditional factors include the patients with potentially
      resectable disease based on anatomic and biologic criteria and with Eastern
      Cooperative Oncology Group (ECOG) performance status of 2 or more. The definition
      of BR-PDAC requires one or more positive dimensions (e.g. A, B, C, AB, AC, BC or
      ABC). The present definition acknowledges that resectability is not just about
      the anatomic relationship between the tumor and vessels, but that biological and
      conditional dimensions are also important. The aim in presenting this consensus
      definition is also to highlight issues which remain controversial and require
      further research.

PMID- 29191515
TI  - Mapping the spatial distribution of Aedes aegypti and Aedes albopictus.
AB  - Mosquito-borne infectious diseases, such as Rift Valley fever, Dengue,
      Chikungunya and Zika, have caused mass human death with the transnational
      expansion fueled by economic globalization. Simulating the distribution of the
      disease vectors is of great importance in formulating public health planning and
      disease control strategies. In the present study, we simulated the global
      distribution of Aedes aegypti and Aedes albopictus at a 5*5km spatial resolution
      with high-dimensional multidisciplinary datasets and machine learning methods
      Three relatively popular and robust machine learning models, including support
      vector machine (SVM), gradient boosting machine (GBM) and random forest (RF),
      were used. During the fine-tuning process based on training datasets of A.
      aegypti and A. albopictus, RF models achieved the highest performance with an
      area under the curve (AUC) of 0.973 and 0.974, respectively, followed by GBM (AUC
      of 0.971 and 0.972, respectively) and SVM (AUC of 0.963 and 0.964, respectively)
      models. The simulation difference between RF and GBM models was not statistically
      significant (p>0.05) based on the validation datasets, whereas statistically
      significant differences (p<0.05) were observed for RF and GBM simulations
      compared with SVM simulations. From the simulated maps derived from RF models, we
      observed that the distribution of A. albopictus was wider than that of A. aegypti
      along a latitudinal gradient. The discriminatory power of each factor in
      simulating the global distribution of the two species was also analyzed. Our
      results provided fundamental information for further study on disease
      transmission simulation and risk assessment.

PMID- 29191514
TI  - Perceived neighborhood characteristics predict severity and emotional response to
      daily stressors.
AB  - RATIONALE: Neighborhood characteristics may influence health and well-being
      outcomes through stressors in daily life. OBJECTIVES: This study tested whether a
      varied set of perceived characteristics of neighborhood (i.e., social cohesion,
      safety, aesthetic quality, violence) predicted stressor frequency and severity as
      well as negative emotional responses to stressors. We predicted greater reported
      cohesion and safety and less violence would be associated with less frequent
      stressor exposure and severity and less intense negative affect following
      stressors; we conducted subsequent tests of neighborhood aesthetic quality as a
      predictor. METHODS: Participants (n = 233, age 25-65 years) were residents in a
      socio-economically, racially, and ethnically diverse zip code in Bronx, New York,
      most who participated in the Effects of Stress on Cognitive Aging, Physiology and
      Emotion study between 2012 and 2013. They provided demographic information and
      neighborhood ratings, then participated in the EMA protocol in which they
      completed brief smartphone surveys of current negative affect and stressor
      exposure, severity, and recency, five times daily for 14 days. RESULTS: No coded
      neighborhood characteristic was related to the frequency of stressors.
      Individuals who reported greater neighborhood violence, however, rated their
      stressors as more severe. Individuals rating their neighborhood lower in safety
      or aesthetic quality, or higher in violence, had greater negative affect
      following stressors. CONCLUSION: Even among people living within the same zip
      code, individual differences in perceptions of neighborhood predict how stressful
      they appraised stressors in daily life to be and how much negative affect they
      reported following stressors.

PMID- 29191517
TI  - Potential risk of a liver fluke Opisthorchis viverrini infection brought by
      immigrants from prevalent areas: A case study in the lower Northern Thailand.
AB  - Considering the long lifespan of the liver fluke Opisthorchis viverrini, human
      mobility from prevalent regions to other neighboring areas has the possibility to
      disperse carriers and complicate the opisthorchiasis problem. To evaluate this,
      mass screening of the fluke infection was conducted in nine communities of lower
      Northern Thailand, combined with a questionnaire survey to distinguish the
      participant's origin. The liver fluke infection was found in 70 individuals
      (7.2%) of the examined 971 stool samples from seven communities, with light
      intensity providing small numbers of eggs in the examined stool. Prevalence in
      the positive communities varied from 2.1% to 28.7%. As a result of generalized
      linear mixed models fitting, regional origin and raw-fish eating habits were
      stably selected as variables affecting the parasite infection while occupation
      and educational background were secondary ones. Majority of the infected cases
      (64.3%) were found from the immigrants of northeastern Thailand (the fluke
      prevalent region), providing 2.28-2.42 times higher infectious risk on average
      against the local residents. Daily consumption of raw fish averaged a 3.12-3.60
      times higher risk compared to those with no raw-fish eating habit. Our findings
      suggest that people's origin and moving history deserve further attentions in
      health promotion programs including education for safe eating.

PMID- 29191516
TI  - Sero-prevalence of Bovine Brucellosis and associated risk factors in mbeya
      region, Southern highlands of Tanzania.
AB  - A cross-sectional study was conducted to establish the seroprevalence of
      brucellosis and associated risk factors in indigenous and exotic breeds of cattle
      from 178 farms in Mbeya region. A total of 1211 cattle (929exotic cattle from 108
      commercial farms and 282 indigenous cattle from 70 traditional farms) were tested
      for Brucella antibodies using the Rose Bengal Plate Test (RBPT) and competitive
      Enzyme Linked Immunosorbent Assay (c-ELISA) as screening and confirmatory tests,
      respectively. The overall animal-level seroprevalence was 9.3%; 11.3% (95% CI:
      9.4-13.5) in indigenous cattle and 2.8% (95% CI:1.4-5.6) in exotic cattle.
      Further, the overall herd level seroprevalence was 32.0%; 50.5% (95% CI: 40.9
      59.9) in indigenous cattle and 4.2% (95% CI: 1.3-12.4) in exotic cattle.
      Infections were higher in cattle aged 6-10 years old, (39.8%; 95% CI: 31.2-49.1)
      followed by those aged 1-5 years (5.8%; 95% CI: 4.8-6.6) and 11-15years old
      (2.7%; 95% CI: 0.8-8). When compared to cattle sampled from herds size of 1-50,
      those sampled from the herd sizes of 51-100 and 101-150 had higher odds of
      brucellosis seropositivity [(OR=3.6, CI: 1.76-7.16, p<0.001) and (OR=3.0, CI:
      1.09-8.04, p=0.033). The odds of seropositivity in animals which calved on
      pasture was 3.0 (CI: 1.1-7.8, p=0.028) compared to those that calved at home.
      Brucella seroprevalence was also observed to vary according to districts, with
      Mbarari district recording the highest (45.4%). It is evident from the study that
      Brucellosis is present in Mbarari, Mbeya and Momba districts of Mbeya Region. The
      findings of this study provide some baseline data that could contribute to the
      design and implementation of brucellosis control measures in the study areas.

PMID- 29191518
TI  - New paleoparasitological investigations from the pre-inca to hispanic contact
      period in northern Chile.
AB  - Paleoparasitological studies have demonstrated that changes in environment or
      culture are reflected in the patterns of parasitic infection diseases in
      populations worldwide. The advent of agriculture and animal domestication, with
      its accompanying reduction in human mobility and expanding population involves
      changes in or emergence of, parasites, the so-called first epidemiological
      transition. Cultural processes related to territory occupation contribute to both
      loss and acquisition of parasites. The archaeological site Lluta 57 in the Lluta
      Valley, Chile, provides a chronology of the transition from the pre-Inca or Late
      Intermediate Period (LIP), through the Late or Inca Period (LP), to the Hispanic
      Contact Period (HCP), providing the possibility of evaluating this
      epidemiological transition. The aim of this study was to conduct a
      paleoparasitological investigation of to gain insight into the dynamics of
      parasitism in Lluta people throughout the Inca expansion. Fourteen human
      coprolites from the three periods were rehydrated, submitted to spontaneous
      sedimentation, and examined by light microscopy for the presence of intestinal
      parasite eggs, pollen grains, and micro-remains. Eggs of four parasites:
      Enterobius vermicularis, Trichostrongylus sp., Trichuris sp., and Eimeria
      macusaniensis were recovered. Frequency, diversity, and number of parasite eggs
      per sample increased over the studied time period. Trichostrongylus sp. and E.
      macusaniensis were recorded in the region for the first time. Enterobius
      vermicularis eggs, absent in the LIP, were present as a hyper-infection in LP.
      The presence of E. macusaniensis is likely related to exploitation of llamas,
      which were used for food and transport and as sacrificial offerings. The
      paleobotanical analysis revealed ten families of pollen grains, as well as
      phytoliths and floral remains. In contrast to parasitological results, a
      diachronic pattern was not detected. Evolution of the settlements, with the
      advent of larger, more densely populated, villages, could have influenced the
      emergence and intensification of transmission of parasites in the region. The
      study showed that the Inca expansion influenced host-parasite-environment
      relationships in the Lluta Valley.

PMID- 29191520
TI  - Novel controlled ionic gelation strategy for chitosan nanoparticles preparation
      using TPP-beta-CD inclusion complex.
AB  - The aim of this study was to develop a novel controlled ionic gelation strategy
      for chitosan nanoparticle preparation to avoid particle aggregation tendency
      associated with conventional ionic gelation process. In this study inclusion
      complexation behaviour of sodium tripolyphosphate (TPP) with beta cyclodextrin
      (beta-CD) has been investigated. The TPP-beta-CD inclusion complex was
      characterized by FT-IR, XRD and DSC techniques. The complexation behaviour was
      also investigated by molecular docking study. The results showed that the TPP
      molecule formed inclusion complex with beta-CD. Further, TPP-beta-CD inclusion
      complex was used to prepare chitosan nanoparticles. The chitosan nanoparticles
      based on TPP-beta-CD inclusion complex had smaller size of 104.2nm+/-0.608, good
      PDI value of 0.346+/-0.016 and acceptable zeta potential of +27.33mV+/-0.416. The
      surface characteristics of chitosan nanoparticles were also observed with
      transmission electron microscopy. Results indicates that TPP-beta-CD inclusion
      complex can be used for the formation of chitosan nanoparticles with smaller and
      more uniform particle size in comparison to conventional TPP based chitosan
      nanoparticles.

PMID- 29191519
TI  - Opisthorchis felineus infection prevalence in Western Siberia: A review of
      Russian literature.
AB  - In this study we reviewed Russian scientific literature (scientific publications,
      book chapters, monographs) published between 1 January 1979 and 31 August 2015
      from two sources: Main database of the Russian Scientific Electronic Library
      (eLIBRARY, http://elibrary.ru/), and the Scientific Medical Library of Siberian
      State Medical University (http://medlib.tomsk.ru/). Specifically, the review
      details the infection prevalence of Opisthorchis felineus (O. felineus) in
      Western Siberia, Russian Federation. From the primary key words screening, 1591
      records were identified from which 32 Russian-language publications were
      relevant. The lowest O. felineus infection rate of 0.4% was reported in Tatarstan
      Republic, and the highest reached 83.9% in the Khanty-Mansiysk Autonomous Okrug.
      The infection prevalence was lower in children than in adults and increased with
      age. O. felineus infection was detected more often in indigenous population than
      in migrants. Infection intensity in western regions (Permskaya, Bryanskaya
      Oblast) was low and varied from 15 to 336 eggs per gram stool (epg), while in
      endemic regions it reached more than 2000 epg. In some settlements the mean
      intensity infection was 5234 epg. The high rates of intensity were registered in
      regions with a high prevalence of infection. Based on obtained data, a map of O.
      felineus infection prevalence in Western Siberia was developed. After mapping the
      results, the highest prevalence was detected in Tyumenskaya Oblast with over 60%,
      while the Tomskaya Oblast had the lowest prevalence at fewer than 19.0%. Khanty
      Mansiysk Autonomus Okrug, Altaiskii Krai, Novosibirskaya Oblast and Omskaya
      Oblast had an average level of O. felineus infection of 20-39%. According to the
      results of the review, Western Siberia must be considered as highly endemic
      region for opisthorchiasis in the Russian Federation. The development of a
      control program specific for the Russian community is warranted.

PMID- 29191521
TI  - The possibility of obtaining marketing authorization of orphan pharmaceutical
      compounding preparations: 3,4-DAP for Lambert-Eaton Myasthenic Syndrome.
AB  - BACKGROUND: Pharmaceutical compounding preparations, produced by (hospital)
      pharmacies, usually do not have marketing authorization. As a consequence, some
      of these pharmaceutical compounding preparations can be picked-up by a
      pharmaceutical company to obtain marketing authorization, often leading to price
      increases. An example is the 3,4-diaminopyridine slow release (3,4-DAP SR)
      tablets for Lambert-Eaton Myasthenic Syndrome (LEMS). In 2009 marketing
      authorization was given for the commercial immediate release phosphate salt of
      the drug, including a fifty-fold price increase compared to the pharmaceutical
      compounding preparation. Obtaining marketing authorization for 3,4-DAP SR by
      academia might have been a solution to prevent this price increase. To determine
      whether the available data of a pharmaceutical compounding preparation with long
      term experience in regular care are adequate to obtain marketing authorization,
      3,4-DAP SR is used as a case study. METHODS: A retrospective qualitative case
      study was performed. Initially, document analysis was executed by collecting the
      required data for marketing authorization in general and whether data of
      Firdapse(r) and 3,4-DAP SR met these requirements. Secondly, the (non-) available
      data of the two formulations were compared with each other to determine the
      differences in availability. RESULTS: At the time of approval, almost all data
      were available for both Firdapse(r) and 3,4-DAP SR. Conversely, much of the data
      used for the approval of Firdapse(r) originated from the 3,4-DAP immediate
      release (3,4-DAP IR) formulation. Only two bioequivalence studies and one
      pharmacology safety study was performed with Firdapse(r) before marketing
      authorization application. CONCLUSIONS: In conclusion, at time Firdapse(r)
      obtained approval, the data available did not differ substantially from 3,4-DAP
      SR, indicating that approval with 3,4-DAP SR would have been possible. We make a
      plea for approval of orphan medicinal products developed and manufactured by
      academic institutions as to keep utilization of these products affordable.

PMID- 29191522
TI  - Cyclodextrin-siRNA conjugates as versatile gene silencing agents.
AB  - Functional siRNAs (luciferase and PLK1) have been conjugated to beta-cyclodextrin
      and the ability of the conjugates to retain gene knockdown activity has been
      assessed by delivery to cancer cell lines using various formulations. Initially
      two formulations used complexation with polycations, namely Lipofectamine 2000
      and an amphiphilic polycationic cyclodextrin. Gene knockdown results for human
      glioblastoma cells (U87) and prostate cancer cells (PC3, DU145) showed that
      conjugation to the cyclodextrin did not reduce gene silencing by the RNA. A third
      mode of delivery involved formation of targeted nanoparticles in which the
      conjugate was first complexed with adamantyl-PEG-ligands (targeting ligand RVG
      peptide or dianisamide) by adamantyl inclusion in the cyclodextrin cavities of
      the conjugates, followed by charge neutralisation with the cationic polymer
      chitosan. Enhanced knockdown was achieved by these ligand-targeted formulations.
      In summary, while this study illustrated the gene silencing efficacy of a simple
      cyclodextrin-siRNA conjugate it is envisaged that future studies will explore the
      use of conjugates with a modified cyclodextrin which would be self-delivering.
      Detailed data such as stability, lysosomal escape etc. will then be reported for
      each conjugate, since this will be appropriate for conjugates which are intended
      to exploit, rather than merely demonstrate, the concept. The present paper was
      intended to demonstrate the viability and generality of this novel concept.

PMID- 29191523
TI  - Criminal offense against healthcare staff of private centers with concerted
      public activity.

PMID- 29191524
TI  - Regional and seasonal variations in heart failure admissions and mortality in the
      USA.

PMID- 29191525
TI  - Apixaban in the prevention of stroke and systemic embolism in patients with non
      valvular atrial fibrillation in France: Rationale and design of the PAROS cross
      sectional study.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia worldwide, and
      its prevalence is expected to increase with population ageing. The use of vitamin
      K antagonists (VKAs) for the prevention of stroke and/or systemic embolism in
      patients with non-valvular atrial fibrillation (NVAF) was recently challenged by
      non-VKA oral anticoagulants (NOACs), demonstrating a favourable risk-benefit
      profile, with reductions in stroke, intracranial haemorrhage and mortality,
      similar major bleeding, but increased gastrointestinal bleeding. Nevertheless,
      data on their use in a "real-life" setting are scarce for France. AIMS: To
      compare the characteristics of patients with AF newly anticoagulated with either
      VKAs or NOACs, to describe the reasons for discontinuing the previous
      anticoagulant strategy and/or choosing the newly initiated anticoagulant
      treatment, and to precisely describe the prescriptions of patients newly
      initiated with apixaban. METHODS: This is a nationwide multicentre non
      interventional cross-sectional study conducted in patients with AF by a
      representative stratified sample of cardiologists in France. Over a 12-month
      accrual period, consecutive patients aged >=18 years with NVAF, for whom
      anticoagulant treatment (VKAs or NOACs) has been initiated within the last three
      months before the index consultation, will be included. The primary outcome will
      be the comparison of anticoagulant-naive patient characteristics, co-morbidities
      and treatment history among the anticoagulant subgroups. Secondary endpoints will
      include a description of the reasons for discontinuing the previous anticoagulant
      strategy and/or for initiating and choosing the newly initiated anticoagulant
      treatment, as well as the prescription conditions of apixaban. CONCLUSION: The
      PAROS study will provide real-life data on the characteristics of NVAF patients
      and their anticoagulant prescription in France.

PMID- 29191526
TI  - Clinical Application of an Open-Source 3D Volume Rendering Software to
      Neurosurgical Approaches.
AB  - BACKGROUND: Preoperative recognition of the anatomic individualities of each
      patient can help to achieve more precise and less invasive approaches. It also
      may help to anticipate potential complications and intraoperative difficulties.
      Here we describe the use, accuracy, and precision of a free tool for planning
      microsurgical approaches using 3-dimensional (3D) reconstructions from magnetic
      resonance imaging (MRI). METHODS: We used the 3D volume rendering tool of a free
      open-source software program for 3D reconstruction of images of surgical sites
      obtained by MRI volumetric acquisition. We recorded anatomic reference points,
      such as the sulcus and gyrus, and vascularization patterns for intraoperative
      localization of lesions. Lesion locations were confirmed during surgery by
      intraoperative ultrasound and/or electrocorticography and later by postoperative
      MRI. RESULTS: Between August 2015 and September 2016, a total of 23 surgeries
      were performed using this technique for 9 low-grade gliomas, 7 high-grade
      gliomas, 4 cortical dysplasias, and 3 arteriovenous malformations. The technique
      helped delineate lesions with an overall accuracy of 2.6 +/- 1.0 mm. 3D
      reconstructions were successfully performed in all patients, and images showed
      sulcus, gyrus, and venous patterns corresponding to the intraoperative images.
      All lesion areas were confirmed both intraoperatively and at the postoperative
      evaluation. CONCLUSIONS: With the technique described herein, it was possible to
      successfully perform 3D reconstruction of the cortical surface. This
      reconstruction tool may serve as an adjunct to neuronavigation systems or may be
      used alone when such a system is unavailable.

PMID- 29191527
TI  - Optic Nerve Meningioma Mimicking Cavernous Hemangioma.
AB  - A 38-year-old woman presented with rapidly worsening, painless right monocular
      vision loss. An examination revealed a visual acuity of 1.4/10 and a central
      scotoma in the right eye. The orbital magnetic resonance imaging (MRI) showed a
      well-delineated ovoid intraconal mass of the right eye, hyperintense on T2
      weighted MRI with homogenous enhancement after contrast injection. The mass
      abutted and displaced the optic nerve. A diagnosis of cavernous hemangioma was
      evoked, which is the most common benign adult orbital mass with these MRI
      features. A biopsy was performed, and the histopathologic examination yielded a
      diagnosis of optic nerve sheath meningioma based on a positive antiprogesterone
      receptor antibody immunostaining. Our case highlights the problem with
      establishing a specific pathologic diagnosis based on MRI alone, even though the
      morphologic aspect is evocative. It is recommended to always conduct a
      histopathologic examination before establishing a specific diagnosis as pathology
      remains the gold standard, especially when the course of action or treatment may
      change, as in our case.

PMID- 29191528
TI  - Web Vessels: Literature Review and Neurointerventional Management.
AB  - OBJECTIVE: The aim of this study was to describe 27 patients with 32 web vessels
      (WVs) from our practice and provide a review of the literature regarding imaging
      diagnostics, clinical presentation, and treatment of WVs. METHODS: A MEDLINE
      search was performed using combinations of the following terms: "stroke in young
      adults," "web," "recurrent stroke," "diaphragm-like," "atypical fibromuscular
      hyperplasia," "atypical fibromuscular dysplasia," "septal fibromuscular
      dysplasia," "septa," "diaphragms," "pseudovalvular folds," and "carotid
      diaphragm." Our series was added in this review. RESULTS: According to location,
      there were 88 carotid WVs (91.66%), 7 vertebral WVs (7.3%), and 1 subclavian WV
      (1.04%). According to clinical presentation, the reported WVs caused stroke in 81
      cases (84.38%). Treatment was supportive care in 46 cases (47.91%), surgery in 33
      cases (35.41%), and an endovascular procedure through angioplasty and stenting in
      17 cases (17.7%). Variables such as age (P = 0.7565), sex (P = 0.6912), and
      location (P = 0.7993) were not shown to be risk factors for stroke in these
      patients. CONCLUSIONS: Although few cases have been reported in the literature,
      the stroke rate in patients with WVs is high. Endovascular treatment is presented
      as an effective form of treatment with no associated morbidities or recurrences
      of ischemic events.

PMID- 29191529
TI  - Health-Related Quality of Life and Posttraumatic Growth in Low-Grade Gliomas in
      China: A Prospective Study.
AB  - OBJECTIVE: The present study aimed to describe the quality of life (QoL) changes
      of survivors of low-grade gliomas (LGGs) 1 year after surgery and to identify
      determinants of QoL with an emphasis on the role of perceived posttraumatic
      growth (PTG). We also tried to examine the linear and quadratic relationship
      between QoL and PTG. METHODS: Two hundred sixty participants were included in the
      final data analysis. The Chinese version of posttraumatic growth inventory and
      the Functional Assessment of Cancer Therapy-Brain scale were used to measure PTG
      and QoL. Hierarchical linear models were fitted to explore the individual time
      trajectories in change of QoL and examine the relationship between demographics,
      clinical features, PTG, and QoL. RESULTS: All dimensions of QoL and PTG increased
      over time except physical well-being, social well-being in QoL, and new
      possibilities in PTG. Time, PTG score, insurance, socioeconomic status, and right
      hemisphere tumor position were positive predictors of QoL. Seizure and depression
      negatively predicted QoL. The quadratic of PTG predicted QoL; however, the
      coefficient of quadratic PTG approached zero. CONCLUSIONS: In general, PTG and
      QoL increased over time. Perceived PTG could significantly predict QoL of LGGs
      survivors 1 year after surgery. A quadratic relation between PTG and QoL was not
      found. Although our data suggested that the growth of QoL may vary across
      different patients, there were only 2 time points in this study. Future studies
      should set more time points to examine this relationship.

PMID- 29191530
TI  - Acute Bilateral Isolated Foot Drop: Changing the Paradigm in Management of
      Degenerative Spine Surgery with Percutaneous Endoscopy.
AB  - BACKGROUND: Acute bilateral isolated foot drop due to lumbar disk prolapse with
      canal stenosis is rare with only 3 cases reported in literature. Our patient was
      managed using the percutaneous full endoscopic technique. This is mainly to
      highlight the ease of access and patient outcome with preoperative and
      postoperative images to support our minimally invasive treatment for this rare
      condition. CASE DESCRIPTION: A 46-year-old male presented with sudden-onset
      severe back pain with bilateral foot drop. Clinical examination showed a
      bilateral L5 radiculopathy with normal perianal sensation. Investigations
      excluded other causes of bilateral foot drop. A magnetic resonance imaging scan
      showed disk herniation at the right L4-L5 (inferior migrated) and L5-S1 level
      (paracentral and extraforaminal) with spinal canal stenosis at the L2-L3 and L5
      S1 levels due to ligamentum flavum hypertrophy. The patient underwent
      percutaneous endoscopic stenosis lumbar decompression at the L2-L3 and L5-S1
      level. At the right L4-L5, L5-S1 level, transforaminal endoscopic diskectomy was
      done using the conventional percutaneous approach. The inferior migrated disk of
      the L4-L5 level was removed using a left L5-S1 contralateral approach. The
      patient recovered with favorable outcome and added benefits of minimally invasive
      surgery. CONCLUSION: Lumbar disk prolapse with canal stenosis should be
      considered in patients presenting with bilateral isolated foot drop. To our best
      knowledge, this is the first report of percutaneous endoscopic treatment to
      address multiple-lumbar-level pathology for this rare condition of acute
      bilateral isolated foot drop.

PMID- 29191531
TI  - Utility of Retrograde Amnesia Assessment Alone, Compared with Anterograde Amnesia
      Assessment in Determining Recovery After Traumatic Brain Injury: Prospective
      Cohort Study.
AB  - BACKGROUND: Posttraumatic amnesia (PTA) after traumatic brain injury (TBI)
      comprises anterograde amnesia (AA), disorientation, and retrograde amnesia (RA).
      However, RA is often neither assessed nor emphasized. A recent study demonstrated
      that although AA and disorientation were both present in non-TBI inpatients
      uniformly taking opioids, RA was absent. This suggests potentially significant
      utility with RA assessment alone since opioids are commonly prescribed post TBI.
      METHODS: We compared RA recovery with AA recovery in a prospective cohort post
      TBI. The Galveston Orientation and Amnesia Test (GOAT) represented a crude test
      for PTA (GOAT <75). AA was primarily assessed using the Westmead PTA Scale, and
      RA was assessed using the GOAT. All patients were prescribed oxycodone. RESULTS:
      Results were obtained (n = 31). While RA recovery coincided with a GOAT recovery
      in 19/31 (61%), AA recovery coincided with GOAT recovery in only 6/31 (19%),
      (chi2 = 11.5, P < 0.001). RA recovery preceded AA recovery in 15/31 (48%), while
      AA recovery preceded RA recovery in 7/31 (23%) (chi2 = 8.6, P = 0.003). Where RA
      recovery less frequently followed AA recovery, temporal lobe contusions were more
      frequent. RA recovery preceded/coincided with AA recovery in 100% of those who
      recovered when AA was defined as *3 consecutive 12/12 scores (as is current
      widespread practice). AA recovery typically followed RA recovery with minimal
      delay. CONCLUSIONS: In the presence of potential in-hospital confounders
      including opioids, RA recovered significantly sooner after TBI than AA and was
      predictive of imminent AA recovery. RA assessment alone therefore had significant
      and novel utility in post-TBI assessment. RA assessment should be routinely
      recorded in all PTA assessment. Given its simplicity and resilience to common
      confounders, RA assessment should also be incorporated into the Glasgow Coma
      Scale.

PMID- 29191532
TI  - The Incidence and Risk Factors of In-Stent Restenosis for Vertebrobasilar Artery
      Stenting.
AB  - BACKGROUND AND OBJECTIVES: In-stent restenosis (ISR) remains a challenge for
      vertebrobasilar artery stenting (VBAS). We aimed to investigate the incidence and
      risk factors of ISR. METHODS: This was a retrospective study. From July 28, 2005,
      to July 30, 2015, patients who received VBAS with an angiographic follow-up time
      of 6 to 12 months after surgery were enrolled. The clinical and angiographic
      issues were recorded and analyzed. RESULTS: In total, 283 patients with 335
      stents were incorporated into the study. Vertebral ostial lesions accounted for
      73.4% (246/335) of the lesions. During the follow-up period, 58 patients with 60
      stents experienced ISR (>50%). Stepwise logistic regression analysis showed that
      the degree of residual stenosis, stent diameter, and alcohol consumption were
      independent predictors of ISR. CONCLUSIONS: Our study demonstrated the incidence
      and risk factors of ISR after VBAS. This retrospective study with the largest
      cohort to date provided insight into the occurrence of ISR after VBAS.

PMID- 29191533
TI  - Oncogenic Viruses in Skull Base Chordomas.
AB  - BACKGROUND: Chordomas are rare tumors assumed to derive from notochordal
      remnants. We believe that a molecular switch is responsible for their malignant
      behavior. The involvement of oncogenic viruses has not been studied, however.
      Thus, in the present study, we investigated the presence of oncogenic viruses in
      chordomas. METHODS: DNA and RNA from snap-frozen chordoma (n = 18) and
      chondrosarcoma (n = 15) specimens were isolated. Real-time PCR or RT-PCR was
      performed to assess the presence of multiple oncogenic viruses, including
      herpesviridea (herpes simplex virus [HSV]-1, HSV-2, Epstein-Barr virus [EBV],
      cytomegalovirus, human herpesvirus [HHV]- 6, HHV-7, and Kaposi's sarcoma
      associated herpesvirus), polyomaviridea (parvovirus B19 [PVB19], BK virus, JC
      virus, Simian virus 40, Merkel cell polyomavirus, human polyomavirus [HPyV]-6,
      and HPyV-7), papillomaviridae, and respiratory viruses. Immunohistochemistry
      (IHC) and in situ hybridization (ISH) were used to validate the positive results.
      RESULTS: PVB19 DNA was detected in 4 of 18 chordomas (22%) and in 1 of 15
      chondrosarcomas (7%). IHC recognizing the VP2 capsid protein of PVB19 showed a
      positive cytoplasmic staining in 44% of the cases (14 of 32). HHV7 DNA was
      present in 6 of the 18 chordomas (33%). Genomic DNA of EBV was found in 22% of
      the samples; however, no positive results were found on ISH. None of the chordoma
      cases showed any presence of DNA from the remaining viruses. CONCLUSIONS: Viral
      involvement in the etiology of chordomas is likely, with PVB19 the most
      distinguishing.

PMID- 29191534
TI  - Microsurgical Clipping of a Giant Middle Cerebral Artery Aneurysm with Successful
      Postoperative Endovascular Mechanical Thrombectomy for Emergent Treatment of
      Large Vessel Occlusion.
AB  - BACKGROUND: Giant intracranial aneurysms (>25 mm) are uncommon. These lesions
      typically manifest clinically due to mass effect, acute hemorrhage, or
      thromboembolic events. To minimize the risk of poor clinical outcome, detailed
      operative planning and a consideration of all neurosurgical and endovascular
      techniques are essential before proceeding with microsurgical clipping of
      ruptured giant aneurysms. CASE DESCRIPTION: We describe a case involving a 15
      year-old male with a ruptured giant middle cerebral artery aneurysm treated with
      microsurgical clipping. After clip application, poor distal flow was demonstrated
      intraoperatively, and emergent angiography demonstrated an M1 occlusion with
      thrombus. A salvage procedure using endovascular mechanical thrombectomy
      reestablished distal flow resulting in a good neurologic outcome. CONCLUSIONS: To
      our knowledge, this is the first case report to describe microsurgical clipping
      of an aneurysm followed by successful postoperative endovascular mechanical
      thrombectomy.

PMID- 29191535
TI  - What Should We Do for Those Hemifacial Spasm Patients Without Efficacy Following
      Microvascular Decompression: Expectation of Delayed Relief or Early Reoperation?
AB  - BACKGROUND: Although microvascular decompression (MVD) has been widely accepted
      as an effective treatment for hemifacial spasm (HFS), some patients may
      experience delayed relief instead of immediate improvement after the surgery. The
      need for and timing of repeat MVD has been controversial to date; thus, we
      conducted the present study with emphasis on those unrelieved patients. METHODS:
      Between January 2010 and December 2014, 3095 patients with idiopathic HFS were
      treated with MVD at XinHua Hospital, Shanghai Jiaotong University School of
      Medicine. Among these patients, 174 (5.6%) reported no symptom relief. Those
      patients without immediate relief were the focus of this study, and all were
      reevaluated at 2 years after MVD surgery. RESULTS: Among these 174 patients, 96
      underwent redo MVD within 1 week of the first procedure (early MVD redo group),
      19 underwent redo between 3 and 12 months after the first procedure (late MVD
      redo group), and 59 were observed (observation group). In the early redo MVD
      group, immediate improvement was reported by all patients except 1, who did not
      experience symptom relief until 3 months later. In the later redo MVD group,
      immediate symptom improvement was reported by 14 of 19 patients. By the end of
      the 2-year follow-up period, 1 recurrence occurred in the early redo MVD group,
      no changes occurred in the later MVD group, and 9 patients improved in the
      observation group. Ultimately, the final rates of symptom relief were 99.0% in
      the early redo MVD group, 73.7% in the later redo MVD group, and 15.3% in the
      observation group (P < 0.01). In the early redo MVD group, postoperative courses
      showed no significant differences between the first and the second operations. In
      the later redo MVD group, 1 patient developed a mild facial palsy and 1 had a
      cerebrospinal fluid leak. CONCLUSIONS: Our findings demonstrate that MVD is the
      most effective treatment for patients with HFS. An early reoperation is easier
      and safer than a later reoperation and may improve the likelihood of immediate
      relief.

PMID- 29191536
TI  - The Enigma of Orbital Compartment Syndrome After Lumbar Spine Surgery in the
      Prone Position: Case Report and Literature Review.
AB  - BACKGROUND: Perioperative visual loss after spinal surgery is a devastating
      complication for the patient and the surgical team. Two known major causes are
      ischemic optic neuropathy and central retinal artery occlusion (CRAO).
      Traditional understanding of CRAO has been consistently related to occurrence of
      periocular trauma and signs of increased intraorbital pressure in addition to
      visual loss. However, such orbital signs are not a feature of any common
      perioperative visual loss syndrome. CASE DESCRIPTION: A 55-year-old woman
      underwent prolonged lumbar decompression and fusion for spinal stenosis under
      general anesthesia in the prone position. At the end of surgery, periocular
      hyperemia, corneal edema, and a tense orbit on the right side were noted.
      Complete internal and external ophthalmoplegia was observed on examination.
      Orbital computed tomography confirmed the clinical diagnosis of orbital
      compartment syndrome. Bony decompression was performed, but the treated eye
      remained blind. Resolution of the complete ophthalmoplegia was observed during
      late follow-up. CONCLUSIONS: In retrospect, patients diagnosed with often
      misunderstood CRAO and ischemic optic neuropathy with orbital signs after spinal
      surgery most likely had orbital compartment syndrome. The inclusion of orbital
      signs in the clinical picture of ischemic optic neuropathy and CRAO is not only
      incorrect but also gives the impression of therapeutic futility, thereby
      preventing successful orbital decompression in a timely fashion.

PMID- 29191537
TI  - Risk Factors and Microbiology of Meningitis and/or Bacteremia After
      Transsphenoidal Surgery for Pituitary Adenoma.
AB  - OBJECTIVE: To investigate the incidence, bacteriologic features, and risk factors
      of posttranssphenoidal surgery (post-TSS) meningitis and/or bacteremia. METHODS:
      This retrospective study included 3242 patients who underwent TSS for pituitary
      adenoma at the Department of Neurosurgery of Peking Union Medical College
      Hospital between January 2012 and December 2016. Clinical data for patients with
      and without post-TSS meningitis and/or bacteremia were compared and analyzed.
      RESULTS: Meningitis and bacteremia developed after 27 (0.8%) and 26 (0.8%)
      procedures, respectively, and 6 patients (0.2%) developed both. Gram-positive
      organisms (coagulase-negative staphylococci, Streptococcus pneumonia, and S
      viridans) predominated in meningitis, whereas gram-negative organisms (Klebsiella
      pneumonia, Enterobacter aerogenes, and Escherichia coli) predominated in
      bacteremia. All identified species were sensitive to amikacin, imipenem, and
      meropenem. Antibiotic treatment cured 52 patients (7 died). In a multivariate
      analysis, the risk of meningitis and/or bacteremia was independently associated
      with diabetes (P < 0.001; odds ratio [OR], 6.06), previous surgery at the same
      location (P < 0.001; OR, 4.23), intraoperative cerebrospinal fluid leakage (P <
      0.001l; OR, 4.63), and an endoscopic approach (P = 0.001; OR, 2.50). CONCLUSIONS:
      Meningitis and/or bacteremia remain critical postoperative complications of TSS
      for pituitary adenoma. The pathogens with drug sensitivity to antibiotics
      differed between meningitis and bacteremia. Early blood and cerebrospinal fluid
      bacterial cultures, drug susceptibility analyses, and appropriate antibiotic
      treatment can help control the rate of infection.

PMID- 29191538
TI  - Collet-Sicard Syndrome Attributable to Extramedullary Plasmacytoma of the Jugular
      Foramen.
AB  - BACKGROUND: Collet-Sicard syndrome is a rare manifestation of skull base disease
      involving the jugular and hypoglossal foramina. We report the first case of
      Collet-Sicard attributable to extramedullary plasmacytoma-multiple myeloma (EP
      MM) and the second case of EP-MM precipitating a jugular foramen syndrome (JFS)
      spectrum disorder. CASE DESCRIPTION: A 59-year-old woman presented with 4 months
      of left aural fullness and pulsatile tenderness, positional vertigo, hoarseness,
      and dysphagia. Examination identified left tongue weakness and nonspecific
      sensory abnormalities of the ear, pharynx, and throat localizing to cranial
      nerves IX-XII. Imaging revealed a 3.4 * 1.4 * 2.8 cm lytic lesion extending from
      the left jugular foramen into the posterior fossa, for which she was referred to
      neurosurgery and otolaryngology for consideration of resection. A second, much
      smaller (1.1-cm) lytic lesion in the left posterior occipital bone was
      incidentally discovered by the surgeon during preoperative consultation. A
      stereotactic biopsy of the occipital lesion was subsequently recommended, which
      identified plasma cell neoplasm. Serum studies and skeletal survey were
      consistent with MM, and a definitive pathologic diagnosis of MM with cranial EP
      was confirmed by bone marrow biopsy. CONCLUSION: Tumors of the jugular foramen
      present with a diverse array of lower cranial nerve deficits, including Collet
      Sicard syndrome, a rare subset of JFS-spectrum diseases. Paragangliomas are the
      most common jugular foramen neoplasms, followed by schwannomas and meningiomas;
      however, many other rare entities have been reported as masqueraders, and
      diligent work-up with consideration for preliminary biopsy is recommended,
      particularly in the presence of additional lesions, equivocal imaging findings,
      or cases arousing high suspicion.

PMID- 29191539
TI  - Prognostic Role of Microembolic Signals After Endovascular Treatment in Anterior
      Circulation Ischemic Stroke Patients.
AB  - BACKGROUND: Endovascular treatment (EVT) is an effective therapy for acute
      ischemic stroke due to large artery occlusion of the anterior circulation. Yet
      some patients do not experience clinical improvement despite successful
      recanalization and reperfusion. The reasons are unknown, but one possible
      explanation is microvessel obstruction downstream. The aim of this study was to
      assess the presence of microembolic signals (MES) with transcranial Doppler and
      define their role as predictors of clinical outcome in stroke patients after EVT.
      MATERIALS AND METHODS: We enrolled 40 consecutive patients (23 men, mean age 65.8
      +/- 7.6 years) with an acute ischemic stroke caused by large artery occlusion of
      the anterior circulation who underwent EVT. Presence and rate of MES were
      assessed by 60-minute transcranial Doppler monitoring at the end of the procedure
      and after 15 days from stroke onset. RESULTS: MES were detected in 65% (26/40) of
      patients after EVT. Ipsilateral carotid occlusion (P = 0.05), >=50% ipsilateral
      carotid stenosis (P = 0.05), incomplete recanalization (P = 0.03), and inadequate
      collaterals (P = 0.04) were associated with a significantly higher MES count,
      which was correlated with a worse functional prognosis (P = 0.03), higher
      mortality (P = 0.02), higher distal embolization burden even outside the original
      ischemic territory (P = 0.02), and higher risk of cardiovascular events (P =
      0.04). CONCLUSIONS: MES monitoring in stroke patients after EVT provides useful
      prognostic information, sheds light on the lack of clinical improvement despite
      successful recanalization, and might guide medical treatment in higher risk
      patients.

PMID- 29191540
TI  - Postoperative Neurologic Outcome in Patients with Pituitary Apoplexy After
      Transsphenoidal Surgery.
AB  - OBJECTIVE: Pituitary apoplexy can cause severe neuro-ophthalmologic or
      endocrinologic sequelae, requiring timely treatment. The present study was
      performed to evaluate postoperative neurologic outcomes and to identify their
      risk factors in patients who underwent transsphenoidal surgery for pituitary
      apoplexy. METHODS: Forty-one consecutive patients with pituitary apoplexy who
      underwent transsphenoidal surgery were reviewed retrospectively. The initial
      rates of visual acuity (VA) decrease, visual field (VF) defect, and ocular palsy
      were 34.1%, 46.3%, and 68.3%, respectively. The median maximal diameter and
      tumoral volume was 2.6 cm (range, 2.0-4.6 cm) and 5.3 cm3 (range, 2.4-38.8 cm3),
      respectively. Seventeen patients (41.5%) underwent surgery within 7 days. The
      median follow-up duration was 45 months (range, 12-196 months). RESULTS: At the
      last follow-up, 62.9% (22/35) of patients had made a full recovery from
      preoperative neurologic deficits, with partial recovery observed in the remaining
      patients. The rates of improvement and full recovery from VA decrease were 92.9%
      and 57.1%, respectively; those from VF defect were 94.7% and 36.8%, respectively;
      and those from ocular palsy were 100.0% and 96.4%, respectively. On multivariate
      analysis, initial visual impairment score (>=20) was the only significant risk
      factor for postoperative neurologic sequelae (P < 0.001; odds ratio, 40.8).
      Surgical timing was not associated with postoperative neurological recovery (P =
      0.733). CONCLUSIONS: Ocular palsy was fully recovered in 96.4% patients with
      pituitary apoplexy after transsphenoidal surgery. Initial visual impairment
      status was found to be more strongly associated with postoperative neurologic
      recovery than surgical timing.

PMID- 29191541
TI  - Subtemporal "Interdural" Surgical Approach for "Giant" Facial Nerve Neurinomas.
AB  - OBJECTIVE: The management issues of 15 cases of giant and dumbbell-shaped facial
      neurinomas that extended both in the middle and posterior cranial fossa are
      reported. MATERIAL AND METHODS: During the period 2002 to June 2017, we
      surgically treated 15 cases of giant and dumbbell shaped facial neurinomas: 10
      males and 5 females ranging from 17-59 years (average 34.2 years). Average
      duration of facial nerve weakness before seeking surgical relief was 49.46
      months. Fourteen patients had varying degrees of hearing disturbance. Seven
      patients had ataxia. The sizes of the tumor ranged from 5.2-8 cm (average being
      6.2 cm). The tumors were in an "interdural" location, both in the middle and in
      the posterior cranial fossa. An extradural subtemporal "interdural" approach was
      used to resect the tumor in both compartments. The dural cover of the tumor
      provided a well-defined surgical plane of dissection. Tumor recurrence was
      observed in 3 cases. The tumor was interdural even at the time of recurrence.
      CONCLUSIONS: Understanding the fact that the facial nerve neurinomas are
      interdural in nature and soft and necrotic in character can allow quick and safe
      surgery with a relatively small surgical exposure.

PMID- 29191542
TI  - Self-Inflicted Drywall Screws in the Sagittal Sinus.
AB  - A 30-year-old right-handed man with a history of schizophrenia presented with 2
      self-inflicted drywall screws in the skull. The patient was sleepy but easily
      arousable; blood tests showed he had taken methamphetamines. Computed tomography
      and computed tomography angiography of the head showed the frontal screw abutted
      left of the superior sagittal sinus, and the posterior screw went through the
      superior sagittal sinus with no extravasation of contrast material at either
      site. Both screws were removed with exposure of the sagittal sinus using U-shaped
      craniectomies. There was no bleeding on the removal of the screws. It appears the
      posterior screw entered between the leaflets of the sagittal sinus dura mater.
      The patient had returned to work without any sequelae 1 month after injury.

PMID- 29191543
TI  - One-Level or Multilevel Interbody Fusion for Multilevel Lumbar Degenerative
      Diseases: A Prospective Randomized Control Study with a 4-Year Follow-Up.
AB  - BACKGROUND: The treatment of multilevel lumbar degenerative disease (LDD) is
      complicated and challenging, and the optimal surgical strategy remains
      controversial. OBJECTIVE: To compare the differences in clinical and radiologic
      outcomes and in complications after 1-level interbody fusion versus multilevel
      interbody fusion for the treatment of multilevel LDD. METHODS: A total of 100
      patients with multilevel LDD were randomized in a 1:1 ratio into the 1-level
      interbody fusion group or the multilevel interbody fusion group. Clinical and
      radiologic results and major complications in the 2 groups were analyzed.
      Clinical outcomes were assessed using the Visual Analog Scale for radicular and
      back pain, the Oswestry Disability Index, and the short-form 36 physical score.
      Clinical status was assessed by the Whitecloud classification. Radiologic
      evaluation included assessment of lumbar lordosis, pelvic incidence, and sacral
      slope. RESULTS: There were no significant differences in clinical and radiologic
      results between the 2 groups. Procedure duration and intraoperative blood loss
      were significantly greater in the multilevel interbody fusion group than in the 1
      level interbody fusion group; the multilevel interbody fusion group also had
      greater incidences of temporary nerve root palsy, wound infection, and adjacent
      segment disease. CONCLUSION: A hybrid technique including 1-level interbody
      fusion and multilevel posterolateral fusion is recommended for patients with
      multilevel LDD.

PMID- 29191544
TI  - Association of SOX17 Gene Polymorphisms and Intracranial Aneurysm: A Case-Control
      Study and Meta-Analysis.
AB  - BACKGROUND: Genome-wide association studies have revealed an association between
      SRY-box 17 (SOX17) gene and intracranial aneurysm (IA) formation. However,
      results were mainly derived from European and Japanese populations. We
      investigated the association between SOX17 gene polymorphisms and IA in a
      homogeneous Korean population. We performed a meta-analysis to assess these
      results in East-Asian populations. METHODS: This cross-sectional study included
      187 age- and sex-matched patients with IA and 372 control subjects. Genetic
      association analysis was performed in the generalized linear model to identify
      associations between 4 single nucleotide polymorphisms and IA, including 95
      patients with ruptured aneurysms and 92 with unruptured aneurysms. The East-Asian
      meta-analysis of 5100 IA cases and 7930 control cases was conducted under an
      inverse variance model. RESULTS: Among 4 single nucleotide polymorphisms that
      passed quality control tests, the minor C allele of rs1072737 was significantly
      associated with IA (odds ratio 0.69, 95% confidence interval 0.49-0.96, P =
      0.03). None of the 4 single nucleotide polymorphisms showed a significant
      association between patients with ruptured and unruptured aneurysms. Meta
      analysis revealed that G alleles of rs10958409 and rs9298506 were significantly
      associated with IA in the East-Asian population after removing study
      heterogeneity (odds ratio 1.11, 95% confidence interval 1.04-1.19, P = 0.0023 and
      odds ratio 1.19, 95% confidence interval 1.07-1.32, P = 0.0016). CONCLUSIONS:
      Identification of genetic variants located near SOX17 is likely to be clinically
      significant for IA formation. rs10958409 and rs9298506 may increase risk of IA in
      East-Asian populations. Our findings may help in the identification of IA
      pathogenesis.

PMID- 29191545
TI  - Intracranial Erdheim-Chester Disease Mimicking Parafalcine Meningioma: Report of
      Two Cases and Review of the Literature.
AB  - BACKGROUND: Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell
      histiocytosis that typically occurs in middle-aged patients. It is usually
      characterized by multifocal osteosclerotic lesions of the long-bones, however
      many cases have extraskeletal involvement. Central nervous system (CNS)
      involvement is common, but isolated CNS involvement at presentation has rarely
      been reported. CASE DESCRIPTION: Here we report two cases of dural-based ECD
      mimicking meningioma on imaging with no other identified sites of disease.
      CONCLUSION: ECD is a rare disease, with isolated CNS involvement reported only a
      few times in the literature. The significance of this presentation requires
      additional study and long-term follow up.

PMID- 29191546
TI  - Patched Closure of Dural Outlet of External Ventricular Drainage Catheter: Better
      Way to Prevent Cerebrospinal Fluid Leakage.
AB  - Postoperative continuous bloody cerebral spinal fluid drainage with external
      ventricular drainage catheter could decrease the incidence of inflammation. But
      the drainage catheter left in place will interrupt the watertight dura matter
      closure. To prevent the related cerebrospinal fluid leakage and subgaleal
      pseudomeningocele after the catheter removal, we developed a patched closure
      method to seal the dural outlet of the drainage catheter with a favorable
      clinical outcome.

PMID- 29191547
TI  - Pial Arteriovenous Fistula: A Brief Review and Report of 14 Surgically Treated
      Cases.
AB  - OBJECTIVE: The authors report their successful experience of treating 14 cases of
      pial arteriovenous fistula (PAVF) by direct surgery. METHODS: During the period
      January 2010 to April 2017, 14 patients with PAVF were treated by surgery. Only
      those patients were selected who had a single arterial feeding channel. There
      were 9 male patients and 5 female patients, and their ages ranged from 5 to 53
      years (average, 19 years). Ten patients were younger than 20 years of age. Five
      patients presented clinical and radiologic features that suggested hemorrhage
      from the PAVF. Ten patients had seizures. Two patients had hemispheric symptoms
      or neurologic deficits at the time of presentation. In 12 patients, there were no
      gross neurologic deficits. The diagnosis was made on the basis of digital
      subtraction angiography in all patients and computed tomographic angiography in 8
      patients. Angiography revealed that the PAVFs in 8 patients were supplied by the
      middle cerebral artery, in 5 patients by the anterior cerebral artery, and in 1
      patient by branches of the basilar artery. Surgical procedures involved
      identification of the site of fistula, obliteration of the feeding artery, and
      resection of the entire venous varix. RESULTS: The PAVF was successfully excluded
      from circulation in all patients. There were no neurologic deficits related to
      the surgical procedure. CONCLUSIONS: Direct surgical resection of the entire PAVF
      is a safe, effective, and probably curative method of treatment.

PMID- 29191548
TI  - Evaluation of Enterprise Stent-Assisted Coiling and Telescoping Stent Technique
      as Treatment of Supraclinoid Blister Aneurysms of the Internal Carotid Artery.
AB  - BACKGROUND: Supraclinoid blister aneurysms (BAs) of the internal carotid artery
      are uncommon and deadly, and appropriate treatment is controversial. Endovascular
      reconstruction may allow treatment through aneurysm isolation. We report a single
      institution experience in the use of Enterprise stent-assisted coiling (ESAC) for
      treating BAs to appraise the safety and efficacy of this technique. METHODS:
      Patients treated with ESAC for a BA at our institution between 2013 and 2016 were
      retrospectively included in this study. Patients' aneurysm characteristics,
      progression status, aneurysm occlusion on follow-up angiography, and modified
      Rankin Scale (mRS) score were recorded and analyzed. Occlusion rates and
      neurologic outcomes were compared between patients treated with a single stent
      and those treated with multiple telescoping stents. RESULTS: Forty-four patients
      were included (17 males; average age, 47.3 years), and ESAC was successfully
      performed in all patients. Immediate postprocedure angiography revealed complete
      occlusion in 23 patients (52.3%), residual neck in 15 (34.1%), and residual
      aneurysm in 6 (13.6%). Twenty patients (45.5%) suffered perioperative cerebral
      vasospasm, and 3 (6.8%) died of secondary ischemic stroke. The duration of follow
      up ranged from 2.5 to 27 months (mean, 11.59 +/- 5.76 months). One patient with
      recurrence was treated with additional coiling, and another patient was treated
      with a covered stent. The use of telescoping stents was associated with a better
      complete aneurysm occlusion rate compared with the use of single stents (84.4%
      [27 of 34] vs. 44.4% [4 of 9]; P = 0.04). Follow-up mRS score was <=1 for 32 of
      41 patients (78.4%). CONCLUSIONS: ESAC to treat BAs is safe, effective, and
      provides good clinical outcomes. ESAC with telescoping stents has a higher follow
      up complete occlusion rate compared with ESAC with single stents.

PMID- 29191549
TI  - Treatment of Brain Arteriovenous Malformations with Hemodynamic Aneurysms: A
      Series of 131 Consecutive Cases.
AB  - BACKGROUND: The natural history of hemodynamic aneurysms (HAs) associated with
      brain arteriovenous malformations (AVMs) remains controversial, with no single
      approach to treatment. The purpose of this study was to justify preventive
      treatment tactics for HAs that pose an increased risk of rupture based on
      hemodynamic studies demonstrating hypertension in the afferent bed after AVM
      exclusion. METHODS: This retrospective analysis included 131 of 1740 patients
      (8%) with brain AVMs and at least 1 aneurysm treated at Burdenko Neurosurgical
      Institute between 2000 and 2016. Treatment consisted of microsurgery,
      endovascular interventions, or a combination of modalities. Patients were
      evaluated with the modified Rankin Scale before and after treatment. RESULTS: A
      total of 205 aneurysms were discovered. Multiple HAs were found in 46 patients
      (35%), and were significantly more often associated with posterior fossa AVMs; in
      addition, most were distally located. There was no difference in the incidence of
      hemorrhage between proximal and distal HAs. Microsurgical treatment was marked by
      high radicalism; 85% of HAs and 94% of AVMs were totally excluded based on
      control studies. In 10 cases, aneurysms were found after AVM removal, including 4
      de novo aneurysms. In 1 case, the aneurysm regressed after AVM treatment. The
      mortality rate was 2.3%. CONCLUSIONS: Preoperative imaging should be carefully
      examined for associated aneurysms before and after surgical treatment. Our data
      suggests that HA exclusion, either as the first step or simultaneously with AVM
      treatment, is most beneficial to patients.

PMID- 29191550
TI  - Lipopolysaccharide- and beta-1,3-glucan-binding protein from Litopenaeus
      vannamei: Purification, cloning and contribution in shrimp defense immunity via
      phenoloxidase activation.
AB  - Lipopolysaccharide- and beta-1,3-glucan-binding protein (LGBP) existed in
      diversity of invertebrates including shrimp plays a crucial role in an innate
      immunity via mediating the recognition of invading pathogens. In this study, LGBP
      was cloned and characterized from the hepatopancreas of Litopenaeus vannamei,
      named as LvLGBP. Its full-length cDNA of 1282 bp contained an open reading frame
      (1101 bp) encoding a peptide of 367 amino acids. The LGBP primary structure
      contained a glycosyl hydrolase domain, two integrin binding motifs, two kinase C
      phosphorylation sites, and two polysaccharide recognition motifs which were
      identified as a polysaccharide binding motif and a beta-1,3-glucan recognition
      motif. The LvLGBP transcripts were expressed mainly in the hepatopancreas. Upon
      challenge with Vibrio parahaemolyticus or white spot syndrome virus (WSSV), the
      LvLGBP mRNA expression was significantly up-regulated to reach a maximum at 48 h
      post injection. Its expression was also induced by lipopolysaccharide (LPS) or
      beta-1,3-glucan stimulation. RNAi-based silencing resulted in the critical
      suppression of LvLGBP expression. Knockdown of LvLGBP gene with co-inoculation by
      V. parahaemolyticus or WSSV led to increase in the cumulative mortality and
      reduce in the median lethal time. Native LGBP was detected only in the
      hepatopancreas as verified by Western blotting. Purified LGBP from the
      hepatopancreas exhibited the agglutinating and binding activity towards Gram
      negative bacterium V. parahaemolyticus with calcium-dependence. Its agglutinating
      activity was dominantly inhibited by LPS with higher potential than beta-1,3
      glucan. Purified LvLGBP could significantly activate the hemocyte phenoloxidase
      activity in the presence of LPS (12.9 folds), while slight activation was
      detected with beta-1,3-glucan (2.0 folds). It could enhance the encapsulation by
      hemocytes but did not have antibacterial activity. These results provided
      evidence that LvLGBP might act as a pathogenic recognition protein to activate
      shrimp immune defense against invading pathogens via the agglutination, binding
      and enhancing encapsulation and phenoloxidase activity of the hemocytes.

PMID- 29191551
TI  - The Drosophila lymph gland is an ideal model for studying hematopoiesis.
AB  - Hematopoiesis in Drosophila melanogaster occurs throughout the entire life cycle,
      from the embryo to adulthood. The healthy lymph gland, as a hematopoietic organ
      during the larval stage, can give rise to two mature types of hemocytes,
      plasmatocytes and crystal cells, which persist into the pupal and adult stages.
      Homeostasis of the lymph gland is tightly controlled by a series of conserved
      factors and signaling pathways, which also play key roles in mammalian
      hematopoiesis. Thus, revealing the hematopoietic mechanisms in Drosophila will
      advance our understanding of hematopoietic stem cells and their niche as well as
      leukemia in mammals. In addition, the lymph gland employs a battery of strategies
      to produce lamellocytes, another type of mature hemocyte, to fight against
      parasitic wasp eggs, making the lymph gland an important immunological organ. In
      this review, the developmental process of the lymph gland and the regulatory
      networks of hematopoiesis are summarized. Moreover, we outline the current
      knowledge and novel insight into homeostasis of the lymph gland.

PMID- 29191552
TI  - Production of bioactive recombinant human Eb-peptide of pro-IGF-I and
      identification of binding components from the plasma membrane of human breast
      cancer cells (MDA-MB-231).
AB  - E-peptide of the pro-Insulin-like growth factor-I (pro-IGF-I) is produced from
      pre-pro-IGF-I by proteolytic cleavage in the post-translational processing. The
      human Eb-peptide (hEb-peptide), derived from the E domain of pro-IGF-IB isoform,
      is a bioactive molecule whose exact physiological role remains elusive.
      Accumulated evidence reported from our laboratory indicated that hEb-peptide
      possesses activity against multiple hallmark characteristics of solid tumor in
      different cancer cell types. In human breast carcinoma cells (MDA-MB-231), it was
      demonstrated that hEb-peptide can promote cell attachment to substratum, inhibit
      colony formation in a semisolid medium, reduce cancer cell invasion, and inhibit
      cancer-induced angiogenesis. Like the action of other peptide hormones, these
      cellular responses triggered by hEb may be initiated through binding to a
      receptor molecule residing on the surface of the cell. Our laboratory and the
      others have previously provided evidence demonstrating the existence of hEb
      peptide specific binding components residing on the cell membrane. In this study,
      we report the isolation and identification of eight protein molecules bound
      reversibly with hEb-peptide from the membrane preparation of MDA-MB-231 cells.
      Some of the identified proteins are known to be present at cell surface and
      function as receptors while the others are not. The functions of these molecules
      reveal strong correlation with the demonstrated activities of hEb-peptide on MDA
      MB-231cells, suggesting hEb-peptide activity on cancer cells might be mediated by
      these molecules.

PMID- 29191553
TI  - AMP and adenosine are both ligands for adenosine 2B receptor signaling.
AB  - Adenosine is considered the canonical ligand for the adenosine 2B receptor
      (A2BR). A2BR is upregulated following kidney ischemia augmenting post ischemic
      blood flow and limiting tubular injury. In this context the beneficial effect of
      A2BR signaling has been attributed to an increase in the pericellular
      concentration of adenosine. However, following renal ischemia both kidney
      adenosine monophosphate (AMP) and adenosine levels are substantially increased.
      Using computational modeling and calcium mobilization assays, we investigated
      whether AMP could also be a ligand for A2BR. The computational modeling suggested
      that AMP interacts with more favorable energy to A2BR compared with adenosine.
      Furthermore, AMPalphaS, a non-hydrolyzable form of AMP, increased calcium uptake
      by Chinese hamster ovary (CHO) cells expressing the human A2BR, indicating
      preferential signaling via the Gq pathway. Therefore, a putative AMP-A2BR
      interaction is supported by the computational modeling data and the biological
      results suggest this interaction involves preferential Gq activation. These data
      provide further insights into the role of purinergic signaling in the
      pathophysiology of renal IRI.

PMID- 29191554
TI  - Structure-based design, synthesis, and binding mode analysis of novel and potent
      chymase inhibitors.
AB  - Based on insight from the X-ray crystal structure of human chymase in complex
      with compound 1, a lactam carbonyl of the diazepane core was exchanged with O
      substituted oxyimino group, leading to amidoxime derivatives. This modification
      resulted in highly potent chymase inhibitors, such as O-phenylamidoxime 5f. X-ray
      crystal structure analysis indicated that compound 5f induced movement of the
      Leu99 and Tyr94 side chains at the S2 site, and the increase in inhibitory
      activity of O-phenyl amidoxime derivatives suggested that the O-phenyl moiety
      interacted with the Tyr94 residue. Surface plasmon resonance experiments showed
      that compound 5f had slower association and dissociation kinetics and the
      calculated residence time of compound 5f to human chymase was extended compared
      to that of amide compound 1.

PMID- 29191555
TI  - Discovery of benzotriazole-azo-phenol/aniline derivatives as antifungal agents.
AB  - A series of benzotriazole-azo-phenol/aniline derivatives were prepared and
      evaluated for their antifungal activities against six phytopathogenic fungi such
      as Fusarium graminearum, Fusarium solani, Alternaria alternate, Valsa mali,
      Botrytis cinerea, and Curvularia lunata. Among them, compounds IIf, IIn, and IIr
      showed a broad-spectrum of potent antifungal activities. Especially some
      compounds displayed 3.5-10.8 folds more potent activities than carbendazim
      against A. alternata and C. lunata. Notably, compounds IIc, IIm, and IIr
      exhibited good protective and therapeutic effects against B. cinerea at 200
      MUg/mL. Their structure-activity relationships were also discussed.

PMID- 29191557
TI  - Synthesis of radioiodinated probes targeted toward matrix metalloproteinase-12.
AB  - Matrix metalloproteinase-12 (MMP-12, macrophage elastase) is a member of the MMP
      family that is responsible for the degradation of extracellular matrix, and is
      associated with the inflammatory process of chronic obstructive pulmonary disease
      (COPD). COPD, characterized by progressive and irreversible airflow obstruction,
      is recently a major cause of mortality and morbidity worldwide. Herein, to
      develop radioiodinated probes for the early diagnosis of COPD, we designed and
      synthesized novel MMP-12-targeted dibenzofuran compounds (1-3) with a variety of
      linker structures (carbamate, amide, and sulfonamide). In competitive enzyme
      activity assays, it was revealed that the linker structures significantly
      affected the inhibitory activity against and selectivity for MMP-12. Compound 1,
      with carbamate linker, demonstrated potent MMP-12 inhibitory activity (IC50 = 8.5
      nM) compared to compound 2, with amide linker, and compound 3, with sulfonamide
      linker. Using bromo-substituted carbamate 13 as a radioiodination precursor,
      [125I]1 was successfully prepared to high radiochemical purity (over 98%) and
      good specific radioactivity (4.1 GBq/MUmol). These results suggest that
      radioiodinated compound 1 is potent as a novel MMP-12-targeted probe.

PMID- 29191556
TI  - Assessment of a pretomanid analogue library for African trypanosomiasis: Hit-to
      lead studies on 6-substituted 2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine
      8-oxides.
AB  - A 900 compound nitroimidazole-based library derived from our pretomanid backup
      program with TB Alliance was screened for utility against human African
      trypanosomiasis (HAT) by the Drugs for Neglected Diseases initiative. Potent hits
      included 2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 8-oxides, which
      surprisingly displayed good metabolic stability and excellent cell permeability.
      Following comprehensive mouse pharmacokinetic assessments on four hits and
      determination of the most active chiral form, a thiazine oxide counterpart of
      pretomanid (24) was identified as the best lead. With once daily oral dosing,
      this compound delivered complete cures in an acute infection mouse model of HAT
      and increased survival times in a stage 2 model, implying the need for more
      prolonged CNS exposure. In preliminary SAR findings, antitrypanosomal activity
      was reduced by removal of the benzylic methylene but enhanced through a
      phenylpyridine-based side chain, providing important direction for future
      studies.

PMID- 29191558
TI  - Where Is the Breakthrough Innovation for Parasite Control?
AB  - The need to improve parasite control to overcome drug-resistant parasite
      populations, and to improve compliance by more convenient drug application
      methods, is evident. While a number of incremental stepwise improvements are
      visible, the big disruptive innovation, an iPhone-equivalent breakthrough, has
      been hard to find. Why?

PMID- 29191559
TI  - Identifying radon priority areas and dwellings with radon exceedances in Bulgaria
      using stored CD/DVDs.
AB  - The implementation of the 2013/59/EURATOM directive in the part related to radon
      exposure imposes challenges for radon measurement methodology and radon survey
      design. Among them is the need to have estimates (preferably direct) of the
      annual average radon concentrations, which can be directly compared to the
      recommended reference levels. On this basis, the surveys should make possible the
      identification of dwellings with indoor radon above the reference levels and
      "radon priority areas" where significant proportion of the dwellings falls in
      this category. The performance of the CD/DVD method for radon measurements as a
      tool to address these issues is presented. A recent large scale field study based
      on the CD/DVD method that was carried out in the suburb area of Sofia, Bulgaria
      is described. Part of the studied area was affected in the past by the uranium
      mining and milling industry. In total 462 disks (CDs and DVDs) taken from 335
      private dwellings from 10 districts in the region were analyzed. The results
      revealed the large heterogeneity in radon distribution in the area, with the
      percentage of dwellings with a 222Rn level above 300 Bq m-3 ranking from about 7%
      to 74%. The district of Yana, for which this percent was 74, was identified as
      the area of highest radon priority in the region. The paper also discusses how
      prompt identification of dwellings with radon above the reference level by
      CD/DVDs can be incorporated within an integrated approach to the radon problem.
      Within this approach the radon hazard is identified shortly after the
      stakeholder's decision to test, which allows fast solution of the problem without
      waiting the long (and usually demotivating) one-year period needed for direct
      results by the commonly used prospective methods.

PMID- 29191560
TI  - MSBIS: A Multi-Step Biomedical Informatics Screening Approach for Identifying
      Medications that Mitigate the Risks of Metoclopramide-Induced Tardive Dyskinesia.
AB  - In 2009 the U.S. Food and Drug Administration (FDA) placed a black box warning on
      metoclopramide (MCP) due to the increased risks and prevalence of tardive
      dyskinesia (TD). In this study, we developed a multi-step biomedical informatics
      screening (MSBIS) approach leveraging publicly available bioactivity and drug
      safety data to identify concomitant drugs that mitigate the risks of MCP-induced
      TD. MSBIS includes (1) TargetSearch (http://dxulab.org/software) bioinformatics
      scoring for drug anticholinergic activity using CHEMBL bioactivity data; (2)
      unadjusted odds ratio (UOR) scoring for indications of TD-mitigating effects
      using the FDA Adverse Event Reporting System (FAERS); (3) adjusted odds ratio
      (AOR) re-scoring by removing the effect of cofounding factors (age, gender,
      reporting year); (4) logistic regression (LR) coefficient scoring for confirming
      the best TD-mitigating drug candidates. Drugs with increasing TD protective
      potential and statistical significance were obtained at each screening step.
      Fentanyl is identified as the most promising drug against MCP-induced TD
      (coefficient: -2.68; p-value<0.01). The discovery is supported by clinical
      reports that patients fully recovered from MCP-induced TD after fentanyl-induced
      general anesthesia. Loperamide is identified as a potent mitigating drug against
      a broader range of drug-induced movement disorders through pharmacokinetic
      modifications. Using drug-induced TD as an example, we demonstrated that MSBIS is
      an efficient in silico tool for unknown drug-drug interaction detection, drug
      repurposing, and combination therapy design.

PMID- 29191561
TI  - Epitope-Specific Immunotherapy Targeting CD4-Positive T Cells in Celiac Disease:
      Safety, Pharmacokinetics, and Effects on Intestinal Histology and Plasma
      Cytokines with Escalating Dose Regimens of Nexvax2 in a Randomized, Double-Blind,
      Placebo-Controlled Phase 1 Study.
AB  - BACKGROUND: Nexvax2(r) is a novel, peptide-based, epitope-specific immunotherapy
      intended to be administered by regular injections at dose levels that increase
      the threshold for clinical reactivity to natural exposure to gluten and
      ultimately restore tolerance to gluten in patients with celiac disease. Celiac
      disease patients administered fixed intradermal doses of Nexvax2 become
      unresponsive to the HLA-DQ2.5-restricted gluten epitopes in Nexvax2, but
      gastrointestinal symptoms and cytokine release mimicking gluten exposure, that
      accompany the first dose, limit the maximum tolerated dose to 150MUg. Our aim was
      to test whether stepwise dose escalation attenuated the first dose effect of
      Nexvax2 in celiac disease patients. METHODS: We conducted a randomized, double
      blind, placebo-controlled trial at four community sites in Australia (3) and New
      Zealand (1) in HLA-DQ2.5 genotype positive adults with celiac disease who were on
      a gluten-free diet. Participants were assigned to cohort 1 if they were HLA-DQ2.5
      homozygotes; other participants were assigned to cohort 2, or to cohort 3
      subsequent to completion of cohort 2. Manual central randomization without
      blocking was used to assign treatment for each cohort. Initially, Nexvax2-treated
      participants in cohorts 1 and 2 received an intradermal dose of 30MUg (consisting
      of 10MUg of each constituent peptide), followed by 60MUg, 90MUg, 150MUg, and then
      eight doses of 300MUg over six weeks, but this was amended to include doses of
      3MUg and 9MUg and extended over a total of seven weeks. Nexvax2-treated
      participants in cohort 3 received doses of 3MUg, 9MUg, 30MUg, 60MUg, 90MUg,
      150MUg, 300MUg, 450MUg, 600MUg, 750MUg, and then eight of 900MUg over nine weeks.
      The dose interval was 3 or 4days. Participants, care providers, data managers,
      sponsor personnel, and study site personnel were blinded to treatment assignment.
      The primary outcome was the number of adverse events and percentage of
      participants with adverse events during the treatment period. This completed
      trial is registered with ClinicalTrials.gov, number NCT02528799. FINDINGS: From
      the 73 participants who we screened from 19 August 2015 to 31 October 2016, 24
      did not meet eligibility criteria, and 36 were ultimately randomized and received
      study drug. For cohort 1, seven participants received Nexvax2 (two with the
      starting dose of 30MUg and then five at 3MUg) and three received placebo. For
      cohort 2, 10 participants received Nexvax2 (four with starting dose of 30MUg and
      then six at 3MUg) and four received placebo. For cohort 3, 10 participants
      received Nexvax2 and two received placebo. All 36 participants were included in
      safety and immune analyses, and 33 participants completed treatment and follow
      up; in cohort 3, 11 participants were assessed and included in pharmacokinetics
      and duodenal histology analyses. Whereas the maximum dose of Nexvax2 had
      previously been limited by adverse events and cytokine release, no such effect
      was observed when dosing escalated from 3MUg up to 300MUg in HLA-DQ2.5
      homozygotes or to 900MUg in HLA-DQ2.5 non-homozygotes. Adverse events with
      Nexvax2 treatment were less common in cohorts 1 and 2 with the starting dose of
      3MUg (72 for 11 participants) than with the starting dose of 30MUg (91 for six
      participants). Adverse events during the treatment period in placebo-treated
      participants (46 for nine participants) were similar to those in Nexvax2-treated
      participants when the starting dose was 3MUg in cohort 1 (16 for five
      participants), cohort 2 (56 for six participants), and cohort 3 (44 for 10
      participants). Two participants in cohort 2 and one in cohort 3 who received
      Nexvax2 starting at 3MUg did not report any adverse event, while the other 33
      participants experienced at least one adverse event. One participant, who was in
      cohort 1, withdrew from the study due to adverse events, which included abdominal
      pain graded moderate or severe and associated with nausea after receiving the
      starting dose of 30MUg and one 60MUg dose. The most common treatment-emergent
      adverse events in the Nexvax2 participants were headache (52%), diarrhoea (48%),
      nausea (37%), abdominal pain (26%), and abdominal discomfort (19%).
      Administration of Nexvax2 at dose levels from 150MUg to 900MUg preceded by dose
      escalation was not associated with elevations in plasma cytokines at 4h. Nexvax2
      treatment was associated with trends towards improved duodenal histology. Plasma
      concentrations of Nexvax2 peptides were dose-dependent. INTERPRETATION: We show
      that antigenic peptides recognized by CD4-positive T cells in an autoimmune
      disease can be safely administered to patients at high maintenance dose levels
      without immune activation if preceded by gradual dose escalation. These findings
      facilitate efficacy studies that test high-dose epitope-specific immunotherapy in
      celiac disease.

PMID- 29191562
TI  - Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich
      Protein Genes PRH1 and PRH2.
AB  - Dental caries is a chronic infectious disease that affects billions of people
      with large individual differences in activity. We investigated whether PRH1 and
      PRH2 polymorphisms in saliva acidic proline-rich protein (PRP) receptors for
      indigenous bacteria match and predict individual differences in the development
      of caries. PRH1 and PRH2 variation and adhesion of indigenous and cariogenic
      (Streptococcus mutans) model bacteria were measured in 452 12-year-old Swedish
      children along with traditional risk factors and related to caries at baseline
      and after 5-years. The children grouped into low-to-moderate and high
      susceptibility phenotypes for caries based on allelic PRH1, PRH2 variation. The
      low-to-moderate susceptibility children (P1 and P4a-) experienced caries from
      eating sugar or bad oral hygiene or infection by S. mutans. The high
      susceptibility P4a (Db, PIF, PRP12) children had more caries despite receiving
      extra prevention and irrespective of eating sugar or bad oral hygiene or S.
      mutans-infection. They instead developed 3.9-fold more caries than P1 children
      from plaque accumulation in general when treated with orthodontic multibrackets;
      and had basic PRP polymorphisms and low DMBT1-mediated S. mutans adhesion as
      additional susceptibility traits. The present findings thus suggest genetic
      autoimmune-like (P4a) and traditional life style (P1) caries, providing a
      rationale for individualized oral care.

PMID- 29191564
TI  - Dynamic ST-Segment Abnormality.
AB  - A 37-year-old man came to the emergency department because of several days of
      intermittent chest pain. An electrocardiogram (ECG) showed sinus rhythm, left
      atrial and left ventricular enlargement, and an early repolarization pattern. A
      second ECG recorded 10 minutes later was strikingly different, with ST-segment
      elevation and large upright T waves in the anterior precordial leads, interpreted
      as evidence of an ST-segment elevation myocardial infarction, and the cardiac
      catheterization team was activated. Closer inspection of the ECG, however,
      disclosed that the changes were because of intermittent ventricular pre
      excitation of the Wolff-Parkinson-White type, and no electrocardiographic,
      echocardiographic, or serum markers of myocardial infarction were found.

PMID- 29191565
TI  - Magnetic Resonance Imaging Correlates of Left Bundle Branch Disease in Patients
      With Nonischemic Cardiomyopathy.
AB  - The pathologic correlates of intraventricular conduction delays in patients with
      nonischemic cardiomyopathy (NIC) have been scarcely investigated. We assessed
      left ventricular (LV) structural, functional, and tissue abnormalities associated
      with intraventricular conduction left bundle disease (LBD), including left
      anterior hemiblock or complete left bundle branch block, in a cohort of patients
      with NIC submitted to cardiovascular magnetic resonance. Twelve-lead
      electrocardiogram and cardiovascular magnetic resonance were performed in 196
      consecutive patients with NIC. The presence and extent of myocardial fibrosis was
      evaluated with late gadolinium enhancement (LGE) technique. Compared with normal
      intraventricular conduction patients, those with LBD were older (66 vs 59 years,
      p = 0.001), had greater LV volumes (p = 0.035 for end-diastolic and p = 0.009 for
      end-systolic volume) and mass (p = 0.034), and showed lower LV ejection fraction
      (33% vs 40%, p = 0.008). LGE was observed more commonly in LBD than in normal
      intraventricular conduction patients and was more often located in the
      ventricular septum (p < 0.001). On multivariate analysis, septal LGE was
      independently associated with a higher likelihood of LBD (odds ratio 6.1, 95%
      confidence interval 2.9 to 12.7, p < 0.001), even after correction for LV
      volumes, mass, and ejection fraction. In conclusion, in NIC, the presence of LBD
      is associated with worse LV remodeling and dysfunction than normal
      intraventricular conduction. Septal fibrosis yielded a 6-fold greater likelihood
      of LBD, independently of the degree of LV dilatation and systolic dysfunction.

PMID- 29191563
TI  - TGF-beta1/p53 signaling in renal fibrogenesis.
AB  - Fibrotic disorders of the renal, pulmonary, cardiac, and hepatic systems are
      associated with significant morbidity and mortality. Effective therapies to
      prevent or curtail the advancement to organ failure, however, remain a major
      clinical challenge. Chronic kidney disease, in particular, constitutes an
      increasing medical burden affecting >15% of the US population. Regardless of
      etiology (diabetes, hypertension, ischemia, acute injury, urologic obstruction),
      persistently elevated TGF-beta1 levels are causatively linked to the activation
      of profibrotic signaling networks and disease progression. TGF-beta1 is the
      principal driver of renal fibrogenesis, a dynamic pathophysiologic process that
      involves tubular cell injury/apoptosis, infiltration of inflammatory cells,
      interstitial fibroblast activation and excess extracellular matrix
      synthesis/deposition leading to impaired kidney function and, eventually, to
      chronic and end-stage disease. TGF-beta1 activates the ALK5 type I receptor
      (which phosphorylates SMAD2/3) as well as non-canonical (e.g., src kinase, EGFR,
      JAK/STAT, p53) pathways that collectively drive the fibrotic genomic program.
      Such multiplexed signal integration has pathophysiological consequences. Indeed,
      TGF-beta1 stimulates the activation and assembly of p53-SMAD3 complexes required
      for transcription of the renal fibrotic genes plasminogen activator inhibitor-1,
      connective tissue growth factor and TGF-beta1. Tubular-specific ablation of p53
      in mice or pifithrin-alpha-mediated inactivation of p53 prevents epithelial G2/M
      arrest, reduces the secretion of fibrotic effectors and attenuates the transition
      from acute to chronic renal injury, further supporting the involvement of p53 in
      disease progression. This review focuses on the pathophysiology of TGF-beta1
      initiated renal fibrogenesis and the role of p53 as a regulator of profibrotic
      gene expression.

PMID- 29191566
TI  - Usefulness of Achieving >=10 METs With a Negative Stress Electrocardiogram to
      Screen for High-Risk Obstructive Coronary Artery Disease in Patients Referred for
      Coronary Angiography After Exercise Stress Testing.
AB  - Functional capacity in exercise stress testing is an independent predictor of
      cardiac events. Routine use of nuclear perfusion imaging increases radiation
      burden and cost. Our goal was to assess the clinical utility of exercise
      functional capacity with stress electrocardiogram (ECG) as an adjunct in
      predicting the presence of high-risk obstructive coronary artery disease (CAD) on
      diagnostic coronary angiography. We performed a retrospective study of patients
      who underwent exercise stress testing for the evaluation of chest pain and
      underwent diagnostic coronary angiography within the subsequent 3 months. High
      risk CAD was defined as coronary artery diameter stenosis of >=70% in the
      proximal left anterior descending artery, >=70% diameter stenosis in 3 major
      epicardial arteries, or >=50% diameter stenosis in the left main artery.
      Univariable and multivariable analyses were performed to identify predictors of
      high-risk CAD. Of the 412 patients, 105 (25%) had high-risk CAD on coronary
      angiography. On multivariate logistic regression, we found that positive stress
      ECG, abnormal stress imaging, left ventricular ejection fraction, and male gender
      were independent predictors of high-risk CAD. The strongest predictor was
      positive stress ECG (hazard ratio 3.16, 95% confidence interval 1.90 to 5.27, p
      <0.001). Functional capacity measures alone were not independent predictors of
      high-risk CAD. Achieving >=10 METs with a negative stress ECG resulted in 94%
      sensitivity and 97% negative predictive value in identifying high-risk CAD. This
      supports the strategy for provisional use of myocardial perfusion imaging in
      patients with low functional capacity and/or abnormal stress ECG to minimize cost
      and radiation exposure.

PMID- 29191568
TI  - Value of the Electrocardiographic (P Wave, T Wave, QRS) Axis as a Predictor of
      Mortality in 14 Years in a Population With a High Prevalence of Chagas Disease
      from the Bambui Cohort Study of Aging.
AB  - We sought to investigate the prognostic value of the electrocardiogram (ECG)
      electrical axes (P wave, T wave and QRS) as predictors of mortality in the 14
      year follow-up of the prospective cohort of all residents >=60 years living in
      the southeastern Brazilian city of Bambui, a population with high prevalence of
      Chagas disease (ChD). Baseline ECG axes were automatically measured with normal
      values defined as follows: P-wave axis 0 degrees  to 75 degrees , QRS axis -30
      degrees  to 90 degrees , and T axis 15 degrees  to 75 degrees . Participants
      underwent annual follow-up visits and death was verified using death
      certificates. Cox proportional hazards regression was used to assess the
      prognostic value of ECG axes for all-cause mortality, after adjustment for
      potential confounders. From 1,742 qualifying residents, 1,462 were enrolled, of
      whom 557 (38.1%) had ChD. Mortality rate was 51.9%. In multivariable adjusted
      models, abnormal P-wave axis was associated with a 48% (hazard ratio [HR] = 1.48
      [95% confidence interval (CI) 1.16-1.88]) increased mortality risk in patients
      with ChD and 43% (HR = 1.43 [CI 1.13-1.81]) in patients without ChD. Abnormal QRS
      axis was associated with a 34% (HR = 1.34 [CI 1.04-1.73]) increased mortality
      risk in patients with ChD, but not in individuals without ChD. Similarly, in the
      ChD group, abnormal T-wave axis was associated with a 35% (HR = 1.35 [CI 1.07
      1.71]) increased mortality, but not in patients without ChD. In conclusion,
      abnormal P-wave, QRS, and T-wave axes were associated with increased all-cause
      mortality in patients with ChD. Abnormal P-wave axis was associated with
      mortality also among those without ChD, being the strongest predictor among ECG
      variables.

PMID- 29191569
TI  - Safety and Efficacy of Beta Blockers in Cocaine-Using Patients With Heart
      Failure.

PMID- 29191567
TI  - Histamine H2 Receptor Polymorphisms, Myocardial Transcripts, and Heart Failure
      (from the Multi-Ethnic Study of Atherosclerosis and Beta-Blocker Effect on
      Remodeling and Gene Expression Trial).
AB  - Myocardial H2 receptor activation contributes to heart failure (HF) in
      preclinical models, and H2 receptor antagonists are associated with decreased HF
      incidence. This study evaluated whether H2 histamine receptor (HRH2) single
      nucleotide polymorphisms (SNPs) are associated with HF incidence and whether
      myocardial transcript abundance is associated with HF recovery. The association
      of SNPs in HRH2 with incident HF was characterized using Cox proportional hazards
      regression among participants in the Multi-Ethnic Study of Atherosclerosis.
      Differences in myocardial HRH2 transcripts were characterized in participants
      with dilated cardiomyopathy comparing 6 "super-responders" with 6 nonresponders
      to beta blockade in the Beta-Blocker Effect on Remodeling and Gene Expression
      Trial. In MESA, no candidate SNP was associated with HF in black, Hispanic, or
      white participants. The rs2241562 minor allele was present only in Chinese
      participants and the adjusted HF hazard among those with 1 or more copies of this
      allele was 3.7, 95% confidence interval 1.0 to 13.4. In BORG, super-responders to
      beta blockade had higher levels of myocardial HRH2 transcript at baseline
      compared with nonresponders (fragments per kilobase per transcript per million
      mapped reads: Variant 2, 5.5 +/- 1.1 compared with 3.2 +/- 0.8 in nonresponders,
      p = 0.002; Variant 1 + 2, 32.1 +/- 7.4 compared with 23.3 +/- 4.2 in
      nonresponders, p = 0.04). In conclusion, the presence of a minor allele at
      rs2241562 was associated with increased HF incidence in Chinese participants.
      Differences in myocardial HRH2 transcript abundance were seen in participants
      with dilated cardiomyopathy who responded to beta blockade. These observations
      support the hypothesis that HRH2 is involved in the pathogenesis of HF.

PMID- 29191570
TI  - The effect of interactions between genetics and cannabis use on neurocognition. A
      review.
AB  - BACKGROUND: Cannabis is one of the most widely-used drugs in industrialized
      countries. It is now well established that cannabis use impacts neurocognition.
      In the intoxication period time episodic memory, working memory and attention are
      impacted and impulsivity is increased. The long-term effects of cannabis use tend
      to be similar. Various internal factors, such as sex differences, modulate this
      impact. It is unclear whether genetic variations can also influence the impact of
      cannabis on neurocognition. We set out to examine the impact of genetic
      variations on neurocognition in cannabis users. METHOD: We conducted a search via
      the PubMed, Web of Science, and ScienceDirect databases to identify studies
      measuring neurocognition and assessing genotypes in the context of cannabis use.
      RESULTS: We included 13 articles. We found that working memory, verbal and visual
      memory and sustained attention are more impacted during intoxication in subjects
      with the Val COMT allele. COMT gene could also modulate sustained attention in
      regular use. The CNR1, AKT1, DBH and 5-HTT/SLC6A4 genes may also modulate
      effects. CONCLUSION: Most of these genes are linked to schizophrenia. A fuller
      understanding of their impact on the effects of cannabis on neurocognition would
      thus help elucidate the mechanisms linking cannabis and psychosis. However,
      evidence is still scant, and more research is needed.

PMID- 29191571
TI  - Distinguish self- and hetero-perceived stress through behavioral imaging and
      physiological features.
AB  - Stress reactivity is a complex phenomenon associated to multiple and multimodal
      expressions. Response to stressors has an obvious survival function and may be
      seen as an internal regulation to adapt to threat or danger. The intensity of
      this internal response can be assessed as the self-perception of the stress
      response. In species with social organization, this response also serves a
      communicative function, so-called hetero-perception. Our study presents
      multimodal stress detection assessment - a new methodology combining behavioral
      imaging and physiological monitoring for analyzing stress from these two
      perspectives. The system is based on automatic extraction of 39 behavioral (2D+3D
      video recording) and 62 physiological (Nexus-10 recording) features during a
      socially evaluated mental arithmetic test. The analysis with machine learning
      techniques for automatic classification using Support Vector Machine (SVM) show
      that self-perception and hetero-perception of social stress are both close but
      different phenomena: self-perception was significantly correlated with hetero
      perception but significantly differed from it. Also, assessing stress with SVM
      through multimodality gave excellent classification results (F1 score values:
      0.9+/-0.012 for hetero-perception and 0.87+/-0.021 for self-perception). In the
      best selected feature subsets, we found some common behavioral and physiological
      features that allow classification of both self- and hetero-perceived stress.
      However, we also found the contributing features for automatic classifications
      had opposite distributions: self-perception classification was mainly based on
      physiological features and hetero-perception was mainly based on behavioral
      features.

PMID- 29191572
TI  - Th17 cells in primary Sjogren's syndrome: Pathogenicity and plasticity.
AB  - Th17 cells play an important physiological role at mucosal barriers, and are
      involved in inflammatory responses to pathogens. Th17 cells and their signature
      cytokine IL-17 are also present in salivary gland lesions of primary Sjogren's
      syndrome (pSS) patients and can be elevated in their peripheral blood. In pSS
      patients, clear correlations between increased Th17 cell activity and symptoms of
      the disease have not been found, but Th17 cells may contribute to disease
      progression, for example by supporting autoreactive B cell responses. In mouse
      models of pSS, Th17 cells play an important role in pathogenesis, particularly at
      disease onset, when there is a disturbed balance between T effector and T
      regulatory cells. Studying the pathogenicity of Th17 cells in humans is
      complicated due to the plasticity of this cell subset, allowing them to obtain
      different effector functions depending on the local environment. Th17 cells can
      develop towards Th17.1 cells, producing both IL-17 and IFN-gamma, or even towards
      Th1-like cells producing IFN-gamma in the absence of IL-17. These effector
      subsets may be more pathogenic than bona fide Th17 cells. Co-expression of IFN
      gamma by Th17 cells has been shown to promote chronic inflammation in several
      autoimmune diseases and may also contribute to pSS pathogenesis. In line with the
      noticeable role of IL-17 in pSS mouse models, interference with Th17 cell
      generation, recruitment or effector functions (e.g. IL-17 inhibition) can prevent
      or ameliorate disease in these models. Therapies targeting Th17 cells or IL-17
      have not been tested so far in pSS patients, although treatment with rituximab
      seems to lower local and systemic IL-17 protein levels, and to a lesser extent
      also chemokine receptor-defined Th17 cells. In this review we discuss current
      knowledge of pathogenicity and plasticity of Th17 cells in human pSS and murine
      models of pSS. We postulate that plasticity towards Th17.1 cells in pSS may
      enhance pathogenicity of Th17 cells at the main target sites of the disease, i.e.
      salivary and lacrimal glands.

PMID- 29191573
TI  - Excessive interferon-alpha signaling in autoimmunity alters glycosphingolipid
      processing in B cells.
AB  - Excessive interferon-alpha (IFN-alpha) production by innate immune cells is a
      hallmark of autoimmune diseases. What other cell type secretes IFN-alpha and how
      IFN-alpha affects immune cell metabolism and homeostasis in autoimmunity are
      largely unclear. Here, we report that autoimmune B cells, arising from two
      different B cell-specific genetic lesions in mice, secrete IFN-alpha. In
      addition, IFN-alpha, found in abundance in autoimmunity, elicited profound
      changes in the B cell lipidome, increasing their expression of glycosphingolipids
      (GSLs) and leading to their CD1d-mediated depletion of iNKT cells in vitro and in
      vivo. IFN-alpha receptor blockade could reverse the loss of iNKT cells. Excessive
      stimulation of B cells with IFN-alpha altered the expression of enzymes that
      catalyze critical steps in GSL processing, increasing the expressions of
      glucosylceramide synthase (GCS) and globotrihexosylceramide synthase (Gb3S) but
      decreasing that of alpha-galactosidase A (alpha-galA). Inhibiting GCS or
      restoring alpha-galA expression prevented iNKT depletion by IFN-alpha-activated B
      cells. Taken together, our work indicated that excessive IFN-alpha perturbs GSL
      metabolism in B cells which in turn adversely affects iNKT homeostasis.

PMID- 29191574
TI  - [Collapsing focal segmental glomerulosclerosis induced by cytomegalovirus: A case
      report].
AB  - Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome
      in child and adult. The collapsing forms are of poor renal prognosis and are
      usually secondary to viral infections with, first and foremost, the human
      immunodeficiency virus. Among other viral etiologies, cytomegalovirus (CMV) is an
      uncommon cause. We report a case of a 32years-old patient with collapsing focal
      segmental glomerulosclerosis induced by cytomegalovirus with initial acute renal
      failure and proteinuria at 12.4g/24h. The treatment associated ganciclovir during
      7days followed by valganciclovir during 14days and steroids at 1mg/kg/day. Renal
      function improved and proteinuria decreased with this treatment. Proteinuria
      increase again 3weeks after valganciclovir discontinuation while CMV Polymerase
      chain reaction (PCR) was positive. Therefore, valganciclovir has been resumed
      allowing renal function normalization and decrease in proteinuria to 4g/24h after
      negative CMVPCR assay after 15weeks. Anti-CMV therapy combined with steroids
      seems to provide a renal response in case of FSGS induced by CMV even if long
      term prognosis stays uncertain.

PMID- 29191575
TI  - [Lupus nephropathy: Insight in new treatments].
AB  - Systemic lupus erythematosus is a chronic autoimmune disease. Both acquired and
      innate immune systems are involved in the development of this systemic disease.
      Lupus nephritis usually is the most serious manifestation of systemic lupus
      erythematosus, with significant morbidity and mortality. The physiopathological
      development of the renal involvement of lupus has been increasingly elucidated
      over the years and various target therapies have recently been developed. After
      some physiopathological reminders, we discuss the conventional treatment of lupus
      nephritis as well as the various therapeutic advances, in particular the
      contribution and the place of the new target therapies in the treatment of the
      lupus nephritis.

PMID- 29191576
TI  - [Comparison of citrate 4% and heparin as tunneled-catheters-locking solution in
      chronic hemodialysis].
AB  - INTRODUCTION: Citrate 4% is an alternative to heparin as catheter-locking
      solution in chronic hemodialysis patients. We compared catheter dysfunction
      episodes, dialysis adequacy, plasminogen-tissular activators use and costs
      according to catheter-locking solution in our centre. METHODS: Prospective,
      monocentric, cohort study (NephroCare Tassin-Charcot) on 49 prevalent patients in
      chronic hemodialysis. Two main groups were formed according to the prescription
      of catheter-locking solution at the beginning of the study (03/02/2016) and
      followed until 05/10/2016: heparin (n=26) and citrate (n=22). RESULTS: The number
      of diabetic patients was higher in the citrate group (12/22) than in the heparin
      one (5/26; P=0.025). The 2 groups were comparable for the other studied
      variables. We didn't observe any difference in terms of catheter-dysfunction
      (4.23 versus 4.14% in heparin and citrate groups, respectively; P=1.0) and
      dialysis adequacy. The prescription of citrate was associated with lower TPA uses
      (1/604 versus 14/946; P=0.022) and lower costs (1.42 ? for one session versus
      2.94 ?). CONCLUSION: Administration of citrate 4% as a catheter-locking solution
      is not inferior to heparin in terms of catheter-dysfunction episodes, is
      associated with similar dialysis adequacy results, lower plasminogen-tissular
      activators uses and reduced costs in chronic prevalent hemodialysed patients.

PMID- 29191577
TI  - Electrical stimulation of the insular cortex as a novel target for the relief of
      refractory pain: An experimental approach in rodents.
AB  - Cortical electrical stimulation (CES) has shown to be an effective therapeutic
      alternative for neuropathic pain refractory to pharmacological treatment. The
      primary motor cortex(M1) was the main cortical target used in the vast majority
      of both invasive and non-invasive studies. Despite positive results M1-based
      approaches still fail to relieve pain in a significant proportion of individuals.
      It has been advocated that the direct stimulation of cortical areas directly
      implicated in the central integration of pain could increase the efficacy of
      analgesic brain stimulation. Here, we evaluated the behavioral effects of
      electrical stimulation of the insular cortex (ESI) on pain sensitivity in an
      experimental rat model of peripheral neuropathy, and have described the pathways
      involved. Animals underwent chronic constriction of the sciatic nerve in the
      right hind limb and had concentric electrodes implanted in the posterior
      dysranular insular cortex. Mechanical nociception responses were evaluated before
      and at the end of a 15-min session of ESI (60Hz, 210MUs, 1V). ESI reversed
      mechanical hypersensitivity in the paw contralateral to the brain hemisphere
      stimulated, without inducing motor impairment in the open-field test.
      Pharmacological blockade of MU-opioid (MOR) or type 1-cannabinoid receptors
      (CB1R) abolished ESI-induced antinociceptive effects. Evaluation of CB1R and MOR
      spatial expression demonstrated differential modulation of CB1R and MOR in the
      periaqueductal gray matter (PAG) of ESI-treated rats in sub-areas involved in
      pain processing/modulation. These results indicate that ESI induces
      antinociception by functionally modulating opioid and cannabinoid systems in the
      PAG pain circuitry in rats with experimentally induced neuropathic pain.

PMID- 29191578
TI  - Gastrin-releasing peptide attenuates fear memory reconsolidation.
AB  - BACKGROUND: Gastrin Releasing Peptide (GRP) may play a role in fear learning. The
      GRP Receptor is expressed in the basolateral amygdala and hippocampus, and
      central administration of GRP mediates fear learning. The effects of GRP on
      reconsolidation, however, have been minimally explored. Reconsolidation, the
      process by which formed memories are rendered labile following recall, provides a
      window of opportunity for pharmacological intervention. Although evidence
      suggests the window of opportunity to alter reactivated consolidation memory can
      be as long as 6 h, shorter intervals have not been extensively investigated.
      METHOD: Male Sprague-Dawley rats received six 1.0 mA continuous footshocks. 24 h
      later, were re-exposed to the context (shock chamber). Immediately following
      memory retrieval rats received i.p. injection of GRP (10 nmol/kg), Flumazenil (1
      mg/kg), GRP + Flumazenil (10 nmol/kg GRP with 1 mg/kg Flumazenil), or Vehicle.
      Other groups received GRP or Vehicle at 0, 10, 30, or 60 min post-reactivation.
      24 h and 5 days later rats were assessed for fear expression upon re-exposure to
      the fearful stimulus. RESULTS: GRP significantly attenuated the reconsolidation
      of learned fear when administered immediately (but not 10 min or longer)
      following recall. Some of the variability in the impact of treatments aimed at
      disrupting fear memories may be governed, in part, by the time-frame of the
      reconsolidation window. Our results indicate that the effect of immediate
      administration persisted for at least 5 days. Co-administration of benzodiazepine
      receptor antagonist Flumazenil blocked this effect, suggesting the effect is
      mediated via a GABAergic mechanism.

PMID- 29191579
TI  - Prenatal stress increases adult vulnerability to cocaine reward without affecting
      pubertal anxiety or novelty response.
AB  - Prenatal stress (PS) induces long-lasting molecular alterations in brain circuits
      of the offspring and increases the propensity to develop neuropsychiatric
      diseases during adulthood, including mood disorders and drug addiction. A major
      goal of this study was to assess the impact of PS on pubertal behaviour and adult
      vulnerability to cocaine-induced conditioning place preference (CPP). We
      therefore evaluated pubertal novelty response and anxiety-like behaviour in
      control (C) and PS rats, and then, we examined cocaine-induced CPP in those
      animals during adulthood. We found no differences between C and PS groups on
      pubertal behaviour, however, only PS rats showed a significant cocaine-induced
      CPP. To further analyze our results, we classified cocaine-treated rats regarding
      their CPP score in Low CPP or High CPP and we then analysed their pubertal
      behaviour. We found different relations of anxiety-like behaviour to cocaine
      reward as a function of PS exposure: for C group, High CPP and Low CPP had shown
      similar levels of anxiety-like behaviour at puberty; on the contrary, for PS
      group, High CPP had shown lower anxiety-like behaviour than Low CPP rats. This
      study underscores the importance of considering prenatal exposure to stress when
      analysing the relationship between anxiety and cocaine vulnerability. Moreover,
      the evaluation of behavioural traits at puberty opens the possibility of early
      intervention and will allow the development of specific prevention strategies to
      avoid the devastating consequences of drug addiction later in life.

PMID- 29191580
TI  - Anaplastic lymphoma kinase gene rearrangement predicts better prognosis in NSCLC
      patients: A meta-analysis.
AB  - OBJECTIVE: For non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase
      (ALK) rearrangement and epidermal growth factor receptor (EGFR) mutations are
      predictive markers of the treatment benefit from selective tyrosine kinase
      inhibitors (TKI). However, their prognostic roles remained uncertain. Thus, we
      conducted this meta-analysis to evaluate the prognosis of ALK+ NSCLC patients in
      the treatment of surgery, chemotherapy, and/or EGFR-TKI. MATERIALS AND METHODS:
      PubMed, Embase and Cochrane databases were thoroughly searched to identify
      relevant studies. Primary endpoints of this study included overall survival (OS),
      recurrence/progression free survival (RFS/PFS) and objective response rate (ORR).
      All statistical analyses were performed via REVIEW MANAGER (version 5.3).
      RESULTS: In total, 15 studies involving 4981 NSCLC patients were included. This
      study demonstrated that smoking status profoundly influenced prognosis of ALK
      related NSCLC. In the general population with NSCLC, compared with ALK- arm, ALK+
      arm obtained a significantly better prognosis (HR=0.81 for OS, 95% CI=0.72-0.91;
      0.80 for RFS/PFS, 95% CI=0.70-0.90), even after further stratification analysis
      according to disease stage. However, in the non-smoking population with NSCLC,
      compared with ALK- arm, those in the ALK+ arm had a worse prognosis (HR=1.65 for
      OS, 95% CI=1.28-2.12; 1.23 for RFS/PFS, 95% CI=1.05-1.44). Furthermore, ALK+
      patients experienced a significantly higher ORR in pemetrexed-based chemotherapy
      but not in EGFR-TKI. CONCLUSIONS: Smoking status had a profound influence on the
      ALK-related prognosis of NSCLC. ALK rearrangement predicted a better prognosis in
      the general population with NSCLC, but a poor survival in the non-smoking
      population. Therefore, stratification according to smoking status is strongly
      recommended for future studies exploring ALK-related prognosis.

PMID- 29191581
TI  - Prognostic value of HLA-A2 status in advanced non-small cell lung cancer
      patients.
AB  - INTRODUCTION: The class I human leucocyte antigen (HLA) molecules play a critical
      role as an escape mechanism of antitumoral immunity. HLA-A2 status has been
      evaluated as a prognostic factor in lung cancer, mostly in localized disease and
      with inconsistent findings. We evaluated the role of HLA-A2 status as a
      prognostic factor in a large and homogeneus cohort of advanced NSCLC patients.
      METHODS: Advanced NSCLC patients eligible for platinum-based chemotherapy were
      consecutively included in a single center between October 2009 and July 2015 in
      the prospective MSN study (NCT02105168). HLA-A2 status was analysed by flow
      cytometry. Clinical, pathological and molecular data were collected. A Cox model
      was used for prognostic analyses. RESULTS: Of 545 stage IIIB/IV NSCLC patients
      included, 344 (63%) were male, 466 (85%) were smokers, 447 (83%) had PS 0-1, 508
      (93%) had stage IV, 407 (75%) had an adenocarcinoma and median age was 61 years
      (range, 21-84). Incidence of patients with EGFRmut, ALK-positive and KRASmut was
      14% (49/361), 9% (29/333) and 31% (107/350), respectively. The overall rate of
      HLA-A2 positivity was 48%. No association was observed between HLA-A2 status and
      any patient or tumor characteristics analyzed. With a median follow-up of 27.1
      months, median OS was 12.8 months [95%CI 11.0-14.6] in HLA-A2+ vs. 12.5 months
      [95%CI 10.4-15.3] in HLA-A2- patients (HR 1.05 [95%CI 0.86-1.29], p=0.61). Median
      progression-free survival was similar in the two cohorts. CONCLUSION: HLA-A2
      status was not identified as prognostic for benefit in a large advanced NSCLC
      population treated with platinum-based chemotherapy.

PMID- 29191583
TI  - Wolf in Sheep's Clothing: Primary Lung Cancer Mimicking Benign Entities.
AB  - Lung cancer is the most common cancer worldwide. On imaging, it typically
      presents as mass or nodule. Recognition of these typical cases is often
      straightforward, whereas diagnosis of uncommon manifestations of primary lung
      cancer is far more challenging. Lung cancer can mimic a variety of benign
      entities, including pneumonia, lung abscess, postinfectious scarring,
      atelectasis, a mediastinal mass, emphysema and granulomatous diseases.
      Correlation with previous history, clinical and biochemical parameters is
      necessary in the assessment of these cases, but often aspecific and inconclusive.
      Whereas 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography is the
      cornerstone in staging of lung cancer, its role in diagnosis of these uncommon
      manifestations is less straightforward since benign entities can present with
      increased 18F-FDG-uptake and, on the other hand, a number of these uncommon lung
      cancer manifestations do not exhibit increased uptake. Chest Computed Tomography
      (CT) is the imaging modality of choice for both lesion detection and
      characterization. In this pictorial review we present the wide imaging spectrum
      of CT-findings as well as radiologic-pathologic correlation of these uncommon
      lung cancer manifestations. Knowledge of the many faces of lung cancer is crucial
      for early diagnosis and subsequent treatment. A multidisciplinary approach in
      these cases is mandatory.

PMID- 29191582
TI  - Patterns of care and survival among patients with malignant mesothelioma in the
      United States.
AB  - BACKGROUND: Mesothelioma is a rare malignancy that is associated with poor
      survival. This study aimed to describe the patterns of care and subsequent
      survival among malignant mesothelioma patients in the United States, while
      adjusting for patient demographics and comorbidities. METHODS: A random sample of
      patients diagnosed with histologically confirmed mesothelioma in 2011, as
      reported to the National Cancer Institute's Surveillance Epidemiology and End
      Results program, were included. Logistic regression and Cox proportional hazard
      regression were utilized to identify factors associated with receipt of therapy
      and all-cause mortality, respectively, among patients with pleural mesothelioma.
      RESULTS: This study included 389 patients with pleural mesothelioma and 53
      patients with non-pleural mesothelioma. Almost a third (29.3%) of the pleural
      patients and 21.5% of the non-pleural patients received no therapy. Additionally,
      approximately 60% of both patient groups received systemic therapy. Among pleural
      mesothelioma patients, receipt of therapy was less likely among older patients.
      Median survival was 9 months among the pleural patients and 18 months among the
      non-pleural patients. Receipt of either surgery or systemic therapy and
      particularly the combination of these two modalities was associated with better
      all-cause survival. Additionally, among pleural mesothelioma patients, younger
      age and lower socioeconomic status were found to be associated with better all
      cause survival. Comorbidity score was not found to be associated with receipt of
      treatment nor was it independently associated with survival among pleural
      mesothelioma patients. CONCLUSION: These findings indicate the need for efforts
      to ensure equitable application of currently available therapies to all patients.

PMID- 29191585
TI  - Treatment outcomes by histology in REVEL: A randomized phase III trial of
      Ramucirumab plus docetaxel for advanced non-small cell lung cancer.
AB  - OBJECTIVES: Ramucirumab, a recombinant human immunoglobulin G1 monoclonal
      antibody inhibiting vascular endothelial growth factor receptor-2, increased
      overall survival (OS) combined with docetaxel versus docetaxel alone in non-small
      cell lung cancer (NSCLC) in the REVEL trial. Pre-specified exploratory analysis
      examined efficacy and safety by histology. MATERIALS AND METHODS: 1253 patients
      with NSCLC were randomized to receive ramucirumab (10mg/kg; n=628) plus docetaxel
      (75mg/m2) or placebo plus docetaxel (n=625) after disease progression on or after
      platinum-based therapy, with or without bevacizumab or maintenance therapy. OS
      was analyzed using Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence
      intervals (CIs) were obtained using an unstratified Cox proportional hazards
      model. Primary quality-of-life analysis was time to deterioration (TtD) of the
      Lung Cancer Symptom Scale (LCSS) scores using the Kaplan-Meier method and Cox
      regression. RESULTS: Median OS for adenocarcinoma was 11.2 months for ramucirumab
      docetaxel (n = 377) and 9.8 months for placebo-docetaxel (n=348); HR=0.83 (95%
      CI: 0.69-0.99). In squamous disease, median OS was 9.5 months for ramucirumab
      docetaxel (n=157) versus 8.2 months for placebo-docetaxel (n=171); HR 0.88 (95%
      CI: 0.69-1.13). Median OS for other nonsquamous was 10.8 months for ramucirumab
      docetaxel (n=74) and 9.3 months for placebo-docetaxel (n=78); HR=0.86 (95% CI:
      0.59-1.26). Treatment-emergent adverse events were comparable between treatment
      arms across histologic subgroups. TtD for LCSS scores was similar between
      treatment arms in the nonsquamous and squamous subgroups. CONCLUSION: REVEL
      demonstrated similar favorable efficacy and manageable safety for ramucirumab
      docetaxel across histologic subgroups of NSCLC.

PMID- 29191584
TI  - Circulating tumor cells as a predictive biomarker in patients with small cell
      lung cancer undergoing chemotherapy.
AB  - BACKGROUND: There are no biomarkers for assessment of disease burden or activity
      of therapy in SCLC. PATIENTS AND METHODS: We conducted a prospective study
      enumerating serial CTCs in patients with newly diagnosed limited disease (LD) and
      extensive stage (ED) SCLC. CTCs demonstrating DNA damage and apoptosis based on
      gammaH2AX and M30 staining were also assessed. We correlated CTC number with
      disease stage, survival outcomes and tumor burden by RECIST. RESULTS: Between
      03/2011-10/2013, 50 evaluable patients were enrolled (20 LD). Baseline CTC number
      was higher for ED (median CTC 71 vs. 1.5 for LD; p 0.0004). Patients with <5 CTC
      had longer PFS but not OS (11 vs. 6.7 months, p 0.0259 and 15.5 vs. 12.9 months,
      p 0.4357). A higher cutoff (CTC<50 or CTC>=50) was significantly correlated with
      both OS (20.2 vs. 11.8 months, p 0.0116) and PFS (10 vs. 4.8 months, p 0.0002).
      Patients with <5 CTC on day 1 of cycle 2 had longer PFS (10 vs. 3.17 months,
      p<0.001) and OS (18 vs. 9 months, p 0.0001). Patients with an increase in
      gamma2HAX-positive CTCs after chemotherapy had longer OS compared to patients
      without an increase (25.3 vs. 9 months, p 0.15). CONCLUSIONS: This study
      demonstrates that CTCs at baseline and Cycle 2 of chemotherapy correlate with
      disease stage and survival in patients with SCLC, suggesting that CTCs may be
      used as a surrogate biomarker for clinical response. Confirmatory prospective
      clinical trials are needed before we can incorporate routine evaluation of CTCs
      into clinical practice.

PMID- 29191586
TI  - Outcome of radical local treatment of non-small cell lung cancer patients with
      synchronous oligometastases.
AB  - OBJECTIVES: Patients with stage IV non-small cell lung cancer (NSCLC) are
      considered incurable and are mainly treated with palliative intent. This patient
      group has a poor overall survival (OS) and progression free survival (PFS). The
      purpose of this study was to investigate PFS and OS of NSCLC patients diagnosed
      with synchronous oligometastatic disease who underwent radical treatment of both
      intrathoracic disease and metastases. MATERIALS AND METHODS: Patients with NSCLC
      and oligometastatic disease at diagnosis, who were treated with radical intent
      between 2008 and 2016, were included in this observational study. Treatment
      consisted of systemic treatment and radical radiotherapy or resection of the
      intrathoracic disease. Treatment of the metastases consisted of radical or
      stereotactic radiotherapy, surgical resection or radiofrequency ablation. RESULTS
      AND CONCLUSIONS: Ninety-one patients (52% men, mean age 60 years) in good
      performance status were included. Thirty-eight patients (42%) died during follow
      up (median follow-up 35 months). The cause of dead was lung cancer in all
      patients, except one. Sixty-three (69%) patients developed recurrent disease.
      Eleven recurrences (17%) occurred within the irradiated area. For the whole
      group, the median PFS was 14 months (range 2-89, 95%CI 12-16) and the median OS
      was 32 months (range 3-89, 95%CI 25-39). The 1- and 2-year OS rates were 85% and
      58% and the 1- and 2-year PFS rates were 55% and 27%, respectively. Radical local
      treatment of a selected group of NSCLC patients with good performance status
      presenting with synchronous oligometastatic disease resulted in favorable long
      term PFS and OS.

PMID- 29191587
TI  - Phenotypes of lung cancer and statistical interactions between tobacco smoking
      and occupational exposure to asbestos and crystalline silica from a large case
      only study: The CaProMat study.
AB  - OBJECTIVES: The aim of this study was to assess the effect modification of the
      association between tobacco smoking and phenotypes of lung cancer (histological
      type, tumor location, and age at diagnosis) by occupational exposure to asbestos
      or to crystalline silica. MATERIALS AND METHODS: The CaProMat study is a pooled
      case-only study including 7256 male lung cancer cases recruited between 1996 and
      2011 in France and Canada. Two job-exposure matrices (JEMs) were used to assess
      occupational exposure to asbestos and crystalline silica. Statistical
      interactions between tobacco smoking and occupational exposure to asbestos or
      crystalline silica were assessed using unconditional logistic regression models
      for histological type and tumor location and linear regression models for age at
      diagnosis. RESULTS: Tobacco smoking was associated with squamous cell carcinoma
      and small cell carcinomas as well as an earlier age at diagnosis. Additional
      exposure to either asbestos or crystalline silica did not modify the effect of
      tobacco smoking for either histological type or age at diagnosis. Neither tobacco
      smoking nor occupational exposure to asbestos or crystalline silica influenced
      tumor location. CONCLUSIONS: Tobacco smoking was the main factor related to
      histological type and age at diagnosis. Those associations were not modified by
      occupational exposure to asbestos or crystalline silica.

PMID- 29191588
TI  - Timeliness of access to lung cancer diagnosis and treatment: A scoping literature
      review.
AB  - The Institute of Medicine recently called for increased understanding of and
      commitment to timely care. Lung cancer can be difficult to diagnose, resulting in
      delays that may adversely affect survival; rapid diagnosis and treatment
      therefore is critical for enabling improved patient outcomes. This scoping review
      provides an update on timeliness of lung cancer care over the past decade. We
      searched PubMed for English-language articles published from 2007 to 2016 that
      report wait time intervals related to diagnosis and treatment of lung cancer. Two
      authors independently reviewed titles and abstracts for inclusion. Abstracted
      data included sample size, patient population, study type, dates of study, wait
      times, and information on disparities, survival, costs, healthcare utilization,
      and interventions. The final review included 65 studies from 21 different
      countries. A total of 96 unique variations of wait intervals were reported (e.g.,
      time to diagnosis from first pulmonologist visit, imaging, or initial
      evaluation), making comparisons across studies difficult. The most common
      interval was diagnosis to treatment initiation, with reported medians ranging
      from 6 to 45 days. Fourteen articles reported information on survival, 14 on
      healthcare utilization, 18 on disparities, and 14 on interventions; results
      varied by study. Significant variation exists in how access to care time delays
      are reported. Many patients across different facilities and countries appear to
      be facing substantial waits to receive lung cancer diagnosis and care. Further
      research, using common wait-interval metrics, is needed to evaluate and improve
      timeliness of lung cancer diagnosis and treatment.

PMID- 29191589
TI  - Does timeliness of care in Non-Small Cell Lung Cancer impact on survival?
AB  - OBJECTIVES: To measure time intervals in the management of Non-Small Cell Lung
      Cancer (NSCLC) patients, identify factors associated with this and evaluate the
      impact of timeliness of care on survival. MATERIALS AND METHODS: A retrospective
      cohort of South Western Sydney (SWS) patients with newly diagnosed NSCLC from
      2006 to 2012 was identified from the SWSLHD Clinical Cancer Registry. Time
      intervals evaluated in days were "Diagnosis to Initial Treatment" and "Referral
      to Initial Treatment". Treatment included surgery, radiotherapy, systemic therapy
      and palliative care. Negative binomial regression and Cox regression were used to
      identify factors associated with timeliness of care and survival respectively.
      RESULTS: 1926 NSCLC patients were identified of whom 1729 had initial treatment
      recorded. Initial treatment was palliative care in 35% (n=611), radiotherapy in
      29% (n=498), surgery in 18% (n=314) and systemic therapy in 18% (n=306). Median
      time from diagnosis to treatment was 32days (IQR 15-58). Median time from
      specialist referral to treatment was 35days for surgery (IQR 21-49), 21days for
      radiotherapy (IQR 13-32) and 25days (IQR 15-35) for systemic therapy. On
      multivariable analysis, age between 70 and 79 years, ECOG performance status 0-1,
      Stage I-III NSCLC and systemic treatment were associated with longer Diagnosis to
      Treatment: intervals. Diagnosis to Treatment: interval was not associated with
      mortality in Stage I & II NSCLC. A longer interval was associated with reduced
      mortality in Stage III (HR 0.99, 95%CI 0.99-1.0, p=0.03) and Stage IV NSCLC
      (HR=0.99, 95% CI 0.99-0.99, p=0.0008). CONCLUSIONS: At the population level,
      longer Diagnosis to Treatment: time intervals were not associated with adverse
      survival outcomes in NSCLC. However, delays to treatment may impact on other
      outcomes such as patient's psychological wellbeing and quality of life which were
      not measured in this study.

PMID- 29191590
TI  - Clinical predictors of survival in young patients with small cell lung cancer:
      Results from the California Cancer Registry.
AB  - BACKGROUND: Small cell lung cancer (SCLC) is an often lethal disease that
      commonly occurs in older individuals with a history of heavy tobacco use. Limited
      epidemiologic and outcomes data are available on young SCLC patients aged less
      than 50 years of age. We assessed clinical variables related to cause specific
      survival (CSS) of young patients with SCLC. METHODS: SCLC patients in the
      California Cancer Registry diagnosed between 1998 and 2012 were included. Primary
      outcome measure was CSS. Hazard ratios (HR) for CSS were calculated using Cox
      Proportional Hazards (pH) models for all ages & for patients <50 years, adjusted
      for baseline variables: age, gender, stage, race, year of diagnosis, initial
      treatment, socioeconomic status (SES), and location (urban vs. rural). RESULTS:
      We identified 22,863 SCLC patients, of which 975 were less than 50 years of age
      (4.2%). Most patients <50years of age were male (51%), white race (71%), and had
      stage IV disease (60%). A lower proportion of patients aged 50 years or younger
      was diagnosed in later years: from 40% in 1998-2002 to 24% in 2008-2012. For all
      SCLC patients, age less than 50 years was an independent predictor of improved
      CSS (HR=0.82, p<0.0001). Multivariate Cox pH models showed that in younger
      patients, female sex (HR=0.81, p=0.0045), Asian race (HR=0.57, p=0.0075), and
      rural residence (HR=0.75, p=0.042) were associated with better CSS, among other
      variables. CONCLUSIONS: In patients with SCLC, age less than 50 years was an
      independent predictor of improved CSS. Baseline clinical variables associated
      with better CSS were identified. These results have potential clinical
      applications.

PMID- 29191591
TI  - Fine-mapping the MHC region in Asian populations identified novel variants
      modifying susceptibility to lung cancer.
AB  - OBJECTIVES: The polymorphic major histocompatibility complex (MHC) plays a vital
      role in the immune system and drives predisposition to multiple cancers. A number
      of lung cancer-related genetic variants in the MHC have been identified in recent
      genome-wide association studies; however, the causal variants remain unclear.
      MATERIALS AND METHODS: In the present study, we conducted a large-scale fine
      mapping study of lung cancer in the MHC region of 13,945 unrelated Asian
      individuals to search for potential causal variants. We used the recently
      constructed Pan-Asian panel as the reference and imputed eight HLA genes (HLA-A,
      HLC-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1) using SNP2HLA
      software. RESULTS: We identified one single nucleotide polymorphism, rs12333226
      (OR=1.41, P=3.97*10-7), five HLA amino acid polymorphisms in HLA-DRB1 (OR=0.89,
      P=7.51*10-6-8.57*10-6), and one two-digit classic HLA allele HLA-A*11 (OR=0.87,
      P=9.68*10-6) that were strongly associated with the risk of lung cancer.
      Rs12333226 was an expression quantitative trait locus of HLA-A and HLA-H in
      circulating monocytes, and exerted effect on lung cancer risk especially in the
      younger. HLA-DRbeta1 positions 10, 16, and 25 drove the effect of one reported
      SNP rs2395185. The peptide position analysis identified additional lung cancer
      susceptibility amino acid positions, including HLA-DRbeta1 position 30 and 11
      (Pomnibus=6.11*10-5 and 6.91*10-5), HLA-DQa1 47 and 76 (Pomnibus=3.96*10-4 and
      1.41*10-2) and HLA-A 152 (Pomnibus=4.86*10-4). Most of the peptide positions were
      located in the peptide-binding grooves and seemed to affect antigen presentation.
      All the existing and novel variants explained approximately 2.37% of the
      phenotypic variances, while 21.10% was attributed to the variants identified in
      this study. CONCLUSION: We identified seven novel bi-allelic variants and five
      polymorphic amino acid positions in HLA-DRbeta1, HLA-DQalpha1, and HLA-A that
      confer a risk of lung cancer. This finding provides evidence for the substantial
      contributions of HLA class I and II molecules to lung cancer susceptibility.

PMID- 29191592
TI  - Adherence to surveillance guidelines in resected NSCLC: Physician compliance and
      impact on outcomes.
AB  - BACKGROUND: Resected NSCLC guidelines have varying recommendations on appropriate
      post-operative surveillance. There is general consensus that patients require
      follow-up with clinic visits and/or CT scans every 6 months for the first 2
      years. This study evaluated compliance with surveillance guidelines and the
      impact on outcomes. METHODS: The BC Cancer Agency (BCCA) provides cancer control
      for 4.6 million individuals. Inclusion criteria included referred patients from
      2005 to 2010, resected stage Ib/II NSCLC, minimum 2 years follow-up at the BCCA,
      no prior cancer within 5 years. Retrospective chart review collected baseline
      parameters, follow up visits, CT imaging, recurrence and death. RESULTS: 479 were
      referred and 263 were eligible. Baseline characteristics: median age 68, male
      52%, current/former/never smoker 38/52/10%, stage Ib/II 51/49%, squamous/non
      30%/70%. Adherence to visits and/or CT scans every 6 months in 2 years: clinic
      visits 77%, CT scans 35%, visit and/or CT 80%. Recurrence rate was 46% at 2
      years. Surveillance below vs per/above guidelines; metastatic recurrence 57% vs
      79% (p=0.28), curative intent treatment at recurrence 14% vs 9% (p=0.50),
      palliative systemic treatment given 14% vs 34% (p=0.42), DFS 66.6m vs 37.6m
      (p<0.001), OS 76.5m vs 37.7m (p<0.001). CONCLUSIONS: Compliance with follow up
      recommendations for resected NSCLC was 80%. Guideline conformity did not increase
      the rate of curative treatment at recurrence nor did it increase the proportion
      of patients treated with palliative chemotherapy. Better adjuvant treatment and
      surveillance options are needed for resected NSCLC.

PMID- 29191593
TI  - Outcomes in patients with aggressive or refractory disease from REVEL: A
      randomized phase III study of docetaxel with ramucirumab or placebo for second
      line treatment of stage IV non-small-cell lung cancer.
AB  - OBJECTIVES: The REVEL study demonstrated improved efficacy for patients with
      advanced non-small cell lung cancer treated with ramucirumab plus docetaxel,
      independent of histology. This exploratory analysis characterized the treatment
      effect in REVEL patients who were refractory to prior first-line treatment.
      MATERIALS AND METHODS: Refractory patients had a best response of progressive
      disease to first-line treatment. Endpoints included overall survival (OS),
      progression-free survival (PFS), objective response rate (ORR), quality of life
      (QoL), and safety. Kaplan-Meier and Cox proportional hazards regression were
      performed for OS and PFS, and Cochran-Mantel-Haenszel test was used for response.
      QoL was assessed with the Lung Cancer Symptom Scale. Sensitivity analyses were
      performed on subgroups of the intent-to-treat population with limited time on
      first-line therapy. RESULTS: Of 1253 randomized patients in REVEL, 360 (29%) were
      refractory to first-line treatment. Baseline characteristics were largely
      balanced between treatment arms. In the control arm, median OS for refractory
      patients was 6.3 versus 10.3 months for patients not meeting this criterion,
      demonstrating the poor prognosis of refractory patients. Median OS (8.3 vs. 6.3
      months; HR, 0.86; 95% CI, 0.68-1.08), median PFS (4.0 vs. 2.5 months; HR, 0.71;
      95% CI, 0.57-0.88), and ORR (22.5% vs. 12.6%) were improved in refractory
      patients treated with ramucirumab compared to placebo, without new safety
      concerns or further deteriorating patient QoL. CONCLUSIONS: The effect of
      ramucirumab in refractory patients is similar to that in the intent-to-treat
      population. The benefit/risk profile for refractory patients suggests that
      ramucirumab plus docetaxel is an appropriate treatment option even in this
      difficult-to-treat population.

PMID- 29191594
TI  - A phase II trial of carboplatin plus S-1 for elderly patients with advanced non
      small-cell lung cancer with wild-type epidermal growth factor receptor: The
      Okayama Lung Cancer Study Group Trial 1202.
AB  - INTRODUCTION: S-1 is an oral fluoropyrimidine-based combination of tegafur,
      gimeracil, and oteracil potassium. Although the combination of S-1 with
      carboplatin is a first-line chemotherapy regimen for advanced non-small cell lung
      cancer (NSCLC), the efficacy and safety of the regimen in the elderly remain
      unknown. METHODS: The patient inclusion criteria were previously untreated
      advanced NSCLC, wild-type epidermal growth factor receptor, aged 70 years or
      more, and a performance status (PS) of 0-2. The patients received oral S-1
      (40mg/m2, twice daily) for 2 weeks and carboplatin (area under the curve: 5) on
      day 1 every 4 weeks as induction treatment. After four induction cycles, S-1
      alone (40mg/m2, twice daily) was administered for 2 weeks every 4 weeks as a
      maintenance therapy until disease progression. The primary endpoint was the
      overall response rate (ORR), which was expected to exceed 20%, and the secondary
      endpoints included the disease control rate (DCR), progression-free survival
      (PFS), overall survival (OS), and the toxicity profile. The associations between
      clinical outcomes and expression of genes such as thymidylate synthase and
      thymidine phosphorylase in the tumors were evaluated. RESULTS: Thirty-three
      patients were enrolled between March 2013 and June 2015. The median age was 78
      (range 70-89) years, and 51.5% had a PS of 0. The ORR was 30.3% (95% confidence
      interval (CI): 14.6-46.0) and the DCR 57.6% (95% CI: 40.7-74.4). Grade 3/4
      toxicities included thrombocytopenia (42.4%), neutropenia (33.3%), and anemia
      (27.3%). There was one treatment-related death due to aspiration pneumonia
      following febrile neutropenia. The median PFS and OS were 134days (95% CI: 79
      173) and 479days (95% CI: 250-571), respectively. Low thymidine phosphorylase
      expression was associated with the DCR (P<0.01). CONCLUSION: This study met the
      predesigned primary endpoint, and the regimen seems to be a favorable treatment
      option.

PMID- 29191595
TI  - Phase 2 study of intermittent pulse dacomitinib in patients with advanced non
      small cell lung cancers.
AB  - BACKGROUND: Dacomitinib is a second-generation, irreversible epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Pre-clinical data suggest
      that intermittent pulsatile dosing of dacomitinib may result in inhibition of
      EGFR T790M. METHODS: We evaluated safety, pharmacokinetics and efficacy of
      intermittent pulsatile dacomitinib in both molecularly unselected patients and
      patients with lung cancers harboring EGFR T790M (Clinical Trial Registration
      Number NCT01858389). RESULTS: Thirty-eight patients were treated on study with
      pulse dacomitinib; sixteen with EGFR T790M in Cohort A and 22 who were not
      molecularly selected in Cohort B. One patient out of 16 patients in Cohort A had
      a partial response to study therapy (ORR 6.3%, 95% CI 0.2-30.2%). The median
      progression-free survival (PFS) in Cohort A was 2.3 months and median PFS in
      Cohort B was 1.6 months. The adverse event profile was similar to standard daily
      dose dacomitinib with the most frequent treatment-related toxicities occurring in
      >20% of patients being diarrhea, rash, stomatitis, nausea, dry skin, paronychia,
      fatigue, and decreased appetite. CONCLUSION: Intermittent pulsatile dacomitinib
      is safe and relatively well tolerated but is not effective in patients that
      harbor EGFR T790M or in unselected patients with non-small cell lung cancer.

PMID- 29191596
TI  - PD-L1 expression in advanced NSCLC: Insights into risk stratification and
      treatment selection from a systematic literature review.
AB  - Tumors can evade immune detection by exploiting inhibitory immune checkpoints
      such as the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1)
      pathway. Antibodies that block this pathway offer a promising new approach to
      treatment in advanced/metastatic non-small cell lung cancer (NSCLC). A systematic
      review of the literature was conducted to assess the association of PD-L1 with
      important patient and disease characteristics, the prognostic significance of PD
      L1 expressing NSCLC tumors, and the value of PD-L1 as a predictive biomarker of
      response to anti-PD-1/PD-L1 treatments in advanced/metastatic NSCLC. A total of
      35 eligible studies were selected for analysis. Methods used to determine PD-L1
      in NSCLC tissue varied considerably; with different PD-L1 antibodies, antibody
      detection methods, and staining cut-offs. Immunohistochemistry was the most
      frequent type of PD-L1 assay. Overall, study evidence did not support an
      association between PD-L1 expression and gender, age, smoking history, tumor
      histology (adenocarcinoma vs. squamous cell carcinoma), performance status,
      pathologic tumor grade or EGFR/KRAS/ALK mutational status. In several studies,
      high PD-L1 expression was associated with shorter survival compared with low
      expression. Most evidence indicated that patients with high vs. low PD-L1
      expression were more likely to experience treatment benefit with anti-PD-1/PD-L1
      agents (nivolumab, pembrolizumab, durvalumab, atezolizumab, and avelumab) in
      advanced NSCLC. Variability in the methods used to determine PD-L1 expression in
      NSCLC tissue suggests a need for standardized use of well-validated PD-L1
      diagnostic assays. Although considerable research links PD-L1 expression in
      tumors to shorter survival in advanced/metastatic NSCLC, its use as a prognostic
      factor requires more study. As studies of anti-PD-1/PD-L1 agents continue, PD-L1
      is likely to play an important role as a predictive biomarker for selecting
      patients deriving most benefit from anti-PD-1/PD-L1 monotherapy and directing
      patients with lower levels of tumor PD-L1 expression (with a high unmet medical
      need), to alternative treatments, such as combination immunotherapies.

PMID- 29191597
TI  - Anamorelin for advanced non-small-cell lung cancer with cachexia: Systematic
      review and meta-analysis.
AB  - INTRODUCTION: Cancer anorexia-cachexia syndrome (CACS) is characterized by
      involuntary weight loss. CACS is commonly observed in advanced non-small-cell
      lung cancer (NSCLC), and it leads to a poor quality of life (QOL). No effective
      standard treatment exists for this condition. However, anamorelin has reportedly
      caused improvement in patients with several cancers. MATERIALS AND METHODS: We
      conducted a quantitative meta-analysis to explore the efficacy of anamorelin for
      treating CACS in patients with NSCLC. We systematically searched CENTRAL,
      MEDLINE, EMBASE, CINAHL, and OvidSP. We pooled the data and calculated and
      compared total body weight (TBW), lean body mass (LBM), overall survival (OS),
      hand grip strength (HGS), QOL, and adverse events (AEs) between patients treated
      with anamorelin (anamorelin group) and those not (placebo group). RESULT: Six
      randomized controlled trials included 1641 patients with NSCLC. Both TBW and LBM
      were significantly increased in the anamorelin group compared to the placebo
      group (mean differences [MD] 1.78, 95%CI: 1.28-2.28, p<0.00001; MD 1.10, 95%CI:
      0.35-1.85, p=0.004, respectively). The groups showed no difference in OS or HGS
      (hazard ratio 0.99, 95%CI: 0.85-1.14, p=0.84; MD 0.52, 95% CI: -0.09-1.13,
      p=0.09, respectively). Anamorelin significantly improved the QOL (standardized MD
      0.19, 95%CI: 0.08-0.30, p=0.0006). The frequency of any AEs and grade 3 or 4 AEs
      were not significantly different between groups (risk ratio[RR] 1.03, 95%CI: 0.95
      1.10, p=0.49; RR 0.86, 95%CI: 0.48-1.54, p=0.62). CONCLUSION: This analysis
      demonstrated that anamorelin represents a promising treatment option for CACS in
      patients with advanced NSCLC.

PMID- 29191598
TI  - Prospective analysis of patient reported symptoms and quality of life in patients
      with incurable lung cancer treated in a rapid access clinic.
AB  - INTRODUCTION: The Vancouver Rapid Access (VARA) clinic was designed to provide
      palliative radiotherapy and holistic care to patients with incurable lung cancer.
      Analysis of the pilot phase demonstrated improved radiotherapy wait-times and
      access to supportive services compared to standard practice. This study aims to
      prospectively assess the impact of the clinic on patient reported symptoms and
      quality of life. MATERIALS AND METHODS: Patient assessments are completed at
      baseline and by a telephone follow up four-weeks later using Likert scales
      adapted from the Edmonton Symptom Assessment System (scale 0-10) and European
      Organization for Research and Treatment of Cancer questionnaires (scale 1-4).
      Patient reported outcomes at follow-up are compared to baseline using wilcoxon
      signed-rank test for categorical variables and paired sample t-test for
      continuous variables. RESULTS: Baseline data was collected on 125 patients, 109
      received palliative radiotherapy (87%). At the 4 week follow up, 22 patients had
      died. Seventy-one of the remaining 103 patients completed the follow-up
      questionnaire, resulting in a 69% response rate among survivors. The mean patient
      reported overall health score, improved from 4.8 to 6.1 (p<0.01). All respiratory
      symptoms except chest pain (p=0.06) were associated with a statistically
      significant improvement after the clinic, whereas all respiratory symptoms
      improved post radiotherapy. Mean bone pain scores decreased from 5.5 to 2.7
      (p<0.01). Assessment of symptoms secondary to brain metastases is limited by
      small patient numbers. CONCLUSION: The VARA clinic provides timely access to
      palliative radiotherapy and supportive services resulting in improved patient
      reported outcomes. Despite a high symptom and disease burden, patients report
      improved overall health and palliation of respiratory symptoms and bony pain. The
      studies completed on the VARA clinic to date, continue to support its value in
      our center.

PMID- 29191599
TI  - Limited mutagenicity of electronic cigarettes in mouse or human cells in vitro.
AB  - OBJECTIVES: Electronic cigarettes (e-cig), which are promoted as safe
      alternatives to tobacco cigarettes or as aides to smoking cessation, are becoming
      increasingly popular among adult chronic smokers and adolescents experimenting
      with tobacco products. Despite the known presence of toxicants and carcinogens in
      e-cig liquid and vapor, the possible carcinogenic effects of e-cig use in humans
      are unknown. MATERIALS AND METHODS: We have utilized two validated in vitro model
      systems to investigate whether e-cig vapor induces mutation in mouse or human
      cells. We have exposed transgenic mouse fibroblasts in vitro to e-cig vapor
      extracts prepared from three popular brands, and determined the induction of
      mutagenesis in a reporter gene, the cII transgene. Furthermore, we have treated
      the pSP189 plasmid with e-cig vapor extract, transfected human fibroblast cells
      with the e-cig-treated plasmid, and screened for the induced mutations in the
      supF gene. RESULTS AND CONCLUSION: We observed no statistically significant
      increases in relative mutant frequency in the cII transgene or supF gene in the e
      cig treated mouse or human cells, respectively. Our data indicate that e-cig
      vapor extracts from the selected brands and at concentrations tested in this
      study have limited mutagenicity in both mouse and human cells in vitro.

PMID- 29191601
TI  - Clinical significance of tumor cavitation in surgically resected early-stage
      primary lung cancer.
AB  - OBJECTIVES: The prognostic impact of tumor cavitation is unclear in patients with
      early-stage primary lung cancer. The aim of the present study was to examine the
      clinicopathological features and prognoses of patients with pathological stage I
      IIA (p-stage I-IIA) primary lung cancers harboring tumor cavitation. This study
      was conducted according to the eighth edition of the TNM classification for lung
      cancer. MATERIALS AND METHODS: We examined 602 patients with p-stage I-IIA
      primary lung cancer out of 890 patients who underwent pulmonary resection from
      January 2007 through March 2014 and searched for the presence of tumor
      cavitation, which is defined as the presence of air space within the primary
      tumor. RESULTS: A total of 59 out of the 602 patients had tumor cavitation (10%).
      Compared with patients without tumor cavitation, those with tumor cavitation had
      a significantly higher frequency of the following characteristics: high serum
      carcinoembryonic antigen (CEA) level (>=5ng/ml, p=0.027), interstitial pneumonia
      (p=0.0001), high SUVmax value on FDG-PET scan (>=4.2, p=0.023), tumors located in
      the lower lobe (p=0.024), large tumor size (>3cm, p=0.002), vascular invasion
      (66% vs 17%, p<0.0001) and non-adenocarcinoma histology (p=0.025). The overall
      survival period of patients with tumor cavitation was significantly shorter than
      that of patients without tumor cavitation (log-rank test: p<0.0001, 5-year OS
      rate: 56% vs 81%). Tumor cavitation was found to be an independent and
      significant factor associated with poor prognosis in the multivariate analysis
      (hazard ratio: 1.76, 95% confidence interval: 1.02-3.10, p=0.042). CONCLUSIONS:
      Tumor cavitation is an independent factor for poor prognosis in patients with
      resected p-stage I-IIA primary lung cancer. Based on our analyses, patients with
      tumor cavitation should be regarded as a separate cohort that requires more
      intensive follow-up.

PMID- 29191600
TI  - Mig-6 deficiency cooperates with oncogenic Kras to promote mouse lung
      tumorigenesis.
AB  - OBJECTIVES: Lung cancer is the leading cause of cancer related deaths worldwide
      and mutation activating KRAS is one of the most frequent mutations found in lung
      adenocarcinoma. Identifying regulators of KRAS may aid in the development of
      therapies to treat this disease. The mitogen-induced gene 6, MIG-6, is a small
      adaptor protein modulating signaling in cells to regulate the growth and
      differentiation in multiple tissues. Here, we investigated the role of Mig-6 in
      regulating adenocarcinoma progression in the lungs of genetically engineered mice
      with activation of Kras. MATERIALS AND METHODS: Using the CCSPCre mouse to
      specifically activate expression of the oncogenic KrasG12D in Club cells, we
      investigated the expression of Mig-6 in CCSPCreKrasG12D-induced lung tumors. To
      determine the role of Mig-6 in KrasG12D-induced lung tumorigenesis, Mig-6 was
      conditionally ablated in the Club cells by breeding Mig6f/f mice to
      CCSPCreKrasG12D mice, yielding CCSPCreMig-6d/dKrasG12D mice (Mig-6d/dKrasG12D).
      RESULTS: We found that Mig-6 expression is decreased in CCSPCreKrasG12D-induced
      lung tumors. Ablation of Mig-6 in the KrasG12D background led to enhanced
      tumorigenesis and reduced life expectancy. During tumor progression, there was
      increased airway hyperplasia, a heightened inflammatory response, reduced
      apoptosis in KrasG12D mouse lungs, and an increase of total and phosphorylated
      ERBB4 protein levels. Mechanistically, Mig-6 deficiency attenuates the cell
      apoptosis of lung tumor expressing KRASG12D partially through activating the
      ErbB4 pathway. CONCLUSIONS: In summary, Mig-6 deficiency promotes the development
      of KrasG12D-induced lung adenoma through reducing the cell apoptosis in KrasG12D
      mouse lungs partially by activating the ErbB4 pathway.

PMID- 29191602
TI  - LKB1/STK11 mutations in non-small cell lung cancer patients: Descriptive analysis
      and prognostic value.
AB  - BACKGROUND: LKB1/STK11 (STK11) is among the most inactivated tumor-suppressor
      genes in non-small cell lung cancer (NSCLC). While evidence concerning the
      biologic role of STK11 is accumulating, its prognostic significance in advanced
      NSCLC has not been envisaged yet. MATERIALS AND METHODS: This retrospective
      analysis included consecutive NSCLC patients with available STK11 information who
      underwent a platinum-based chemotherapy. STK11 mutational status was correlated
      to clinico-pathological and mutational features. Kaplan-Meier and Cox models were
      used for survival curves and multivariate analyses, respectively. RESULTS: Among
      the 302 patients included, 267 (89%) were diagnosed with stage IIIB/IV NSCLC and
      25 (8%) harbored a STK11 mutation (STK11mut). No statistical differences were
      observed between STK11 status and clinico-pathological variables. We detected a
      significant correlation between STK11 and KRAS status (p=0.008); among the 25
      STK11mut patients, 13 (52%) harbored a concomitant KRAS mutation. Overall
      survival (OS) was shorter for STK11mut (median OS=10.4months) compared to wild
      type patients (STK11wt; median OS=17.3months) in univariate analysis (p=0.085).
      STK11 status did not impact upon OS in multivariate analysis (p=0.45) and non
      significant results were observed for progression-free survival. The co
      occurrence of KRAS and STK11 mutations suggest a trend toward detrimental effect
      in OS (p=0.12). CONCLUSIONS: In our cohort enriched for advanced NSCLC patients
      who received platinum-based chemotherapy, STK11 mutations were not specifically
      associated with clinico-pathological features and they did not impact upon
      survival. We confirm the positive correlation between STK11 and KRAS mutations.
      The co-occurrence of KRAS and STK11 mutations could label a more aggressive
      molecular subtype of NSCLC.

PMID- 29191603
TI  - Serum lipid profile discriminates patients with early lung cancer from healthy
      controls.
AB  - OBJECTIVES: The role of a low-dose computed tomography lung cancer screening
      remains a matter of controversy due to its low specificity and high costs.
      Screening complementation with blood-based biomarkers may allow a more efficient
      pre-selection of candidates for imaging tests or discrimination between benign
      and malignant chest abnormalities detected by low-dose computed tomography (LD
      CT). We searched for a molecular signature based on a serum lipid profile
      distinguishing individuals with early lung cancer from healthy participants of
      the lung cancer screening program. MATERIALS AND METHODS: Blood samples were
      collected from 100 patients with early stage lung cancer (including 31 screen
      detected cases) and from a matched group of 300 healthy participants of the lung
      cancer screening program. MALDI-ToF mass spectrometry was used to analyze the
      molecular profile of lipid-containing organic extract of serum samples in the 320
      1000Da range. RESULTS: Several components of the serum lipidome were detected,
      with abundances discriminating patients with early lung cancer from high-risk
      smokers. An effective cancer classifier was built with an area under the curve of
      0.88. Corresponding negative predictive value was 98% and a positive predictive
      value was 42% when the classifier was tuned for maximum negative predictive
      value. Furthermore, the downregulation of a few lysophosphatidylcholines
      (LPC18:2, LPC18:1 and LPC18:0) in samples from cancer patients was confirmed
      using a complementary LC-MS approach (a reasonable cancer discrimination was
      possible based on LPC18:2 alone with 25% total weighted error of classification).
      CONCLUSIONS: Lipid-based serum signature showed potential usefulness in
      discriminating early lung cancer patients from healthy individuals.

PMID- 29191604
TI  - MHC class II expression in lung cancer.
AB  - BACKGROUND: Immunotherapy is an exciting development in lung cancer research. In
      this study we described major histocompatibility complex (MHC) Class II protein
      expression in lung cancer cell lines and patient tissues. METHODS: We studied MHC
      Class II (DP, DQ, DR) (CR3/43, Abcam) protein expression in 55 non-small cell
      lung cancer (NSCLC) cell lines, 42 small cell lung cancer (SCLC) cell lines and
      278 lung cancer patient tissues by immunohistochemistry (IHC). RESULTS: Seven
      (12.7%) NSCLC cell lines were positive for MHC Class II. No SCLC cell lines were
      found to be MHC Class II positive. We assessed 139 lung cancer samples available
      in the Hirsch Lab for MHC Class II. There was no positive MHC Class II staining
      on SCLC tumor cells. MHC Class II expression on TILs in SCLC was significantly
      lower than that on TILs in NSCLC (P<0.001). MHC Class II was also assessed in an
      additional 139 NSCLC tumor tissues from Medical University of Gdansk, Poland.
      Patients with positive staining of MHC Class II on TILs had longer regression
      free survival (RFS) and overall survival (OS) than those whose TILs were MHC
      Class II negative (2.980 years, 95% CI 1.628-4.332 vs. 1.050 years, 95% CI 0.556
      1.554, P=0.028) (3.230 years, 95% CI 2.617-3.843 vs. 1.390 years, 95% CI 0.629
      2.151, P=0.014). CONCLUSIONS: MHC Class II was expressed both in NSCLC cell lines
      and tissues. However, MHC Class II was not detected in SCLC cell lines or tissue
      tumor cells. MHC Class II expression was lower on SCLC TILs than on NSCLC TILs.
      Loss of expression of MHC Class II on SCLC tumor cells and reduced expression on
      SCLC TILs may be a means of escaping anti-cancer immunity. Higher MHC Class II
      expression on TILs was correlated with better prognosis in patients with NSCLC.

PMID- 29191605
TI  - Inhibition of protein phosphatase 5 suppresses non-small cell lung cancer through
      AMP-activated kinase activation.
AB  - OBJECTIVES: Non-small cell lung cancer (NSCLC) continues to be the top cause of
      cancer death. To improve the treatment of lung cancer, there is necessity to
      identify novel oncogenes and investigate their effects on lung carcinogenesis.
      Protein phosphatase 5 (PP5) has long been known to regulate stress-induced
      apoptosis and cell proliferation. Recently, PP5 has been found overexpressed and
      emerged as a viable therapeutic target in various human cancers, but its role in
      NSCLC remains elusive. MATERIALS AND METHODS: The expression of PP5 in NSCLC cell
      lines (A549, H358, and H460) and human tumor samples were examined. Protein
      phosphatase inhibitors, cantharidin and norcantharidin, were used as proof-of
      concept compounds to investigate the pathological function of PP5 in NSCLC.
      Apoptosis and cellular signaling were analyzed. In vivo efficacy was determined
      in nude mice with H460 xenograft. RESULTS AND CONCLUSION: We found that PP5 was
      more highly expressed in human lung tumor samples than in adjacent normal
      tissues. Overexpression of PP5 promoted cell proliferation, colony formation, and
      sphere-forming ability of A549 cells. Inhibition of PP5 phosphatase activity by
      cantharidin induced significant apoptosis and upregulated AMP-activated protein
      kinase (AMPK) signaling. Importantly, we found that PP5-mediated
      dephosphorylation of AMPK determines the in vitro anti-NSCLC effects of
      cantharidin. Consistent with our in vitro data, PP5 inhibition suppressed H460
      tumor growth and upregulated p-AMPK in tumor samples. Our results demonstrate
      that PP5 inhibition suppresses tumor growth via activating AMPK signaling.
      Targeting oncogenic PP5 represents an attractive therapeutic strategy for
      treating lung cancer.

PMID- 29191606
TI  - Response rates to single-agent chemotherapy after exposure to immune checkpoint
      inhibitors in advanced non-small cell lung cancer.
AB  - INTRODUCTION: Exploratory analysis of clinical trials in various tumor types have
      demonstrated potential improvements in overall response rate (ORR) to
      chemotherapy after exposure to vaccine-based immunotherapy. The objective of this
      retrospective study was to determine if single-agent chemotherapy (3rd-line or
      beyond) would yield improved ORR when given after exposure to programmed death
      (ligand)1 inhibitors (anti-PD1) in metastatic non-small cell lung cancer (NSCLC).
      MATERIALS AND METHODS: We queried the Thoracic GEMINI database of MD Anderson
      Cancer Center for patients treated between 06/12 and 11/16 who received at least
      one single-agent chemotherapy as 3rd-line or beyond, following progression after
      platinum-based chemotherapy and anti-PD1. We evaluated efficacy outcomes to each
      therapy, including ORR by RECIST version 1.1, progression-free survival (PFS),
      and overall survival (OS). RESULTS: Out of 306 anti-PD1-treated patients
      registered in the database, 28 met eligibility criteria - 54% were male, median
      age was 66 years, 82% had adenocarcinoma, and 71% were former/current smokers.
      The anti-PD1 and single-agent chemotherapy most commonly used were nivolumab
      (86%) and docetaxel (50%), respectively. ORR to single-agent chemotherapy after
      exposure to anti-PD1 was 39% (11/28 patients, 8 confirmed). In contrast, ORR to
      first-line chemotherapy in this cohort was 37%. Liver metastasis was the only
      factor associated with response to single-agent chemotherapy on univariate
      analysis (p<0.05). CONCLUSION: In NSCLC patients, the confirmed ORR to single
      agent chemotherapy after immunotherapy exposure was higher as compared to
      historical data from the pre-anti-PD1 era, and approached ORR to first-line
      platinum-based chemotherapy. Further investigation of a possible immunotherapy
      induced chemosensitization effect is warranted.

PMID- 29191607
TI  - PIK3CA mutation as a distinctive genetic feature of non-small cell lung cancer
      with chronic obstructive pulmonary disease: A comprehensive mutational analysis
      from a multi-institutional cohort.
AB  - OBJECTIVES: Non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary
      disease (COPD) have been proposed to have a mutual developmental mechanism, but
      their association has not been fully understood. We aimed to examine the
      association of the mutational landscape of NSCLC with co-morbid COPD. MATERIALS
      AND METHODS: A total of 197 surgical specimens of early stage NSCLC were
      retrospectively collected from two independent sources, namely, the Japan
      Molecular Epidemiology for Lung Cancer Study and the Osaka City University
      Hospital cohort from 2010 to 2013. COPD and its severity were defined by the
      Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and
      grading system. For molecular profiling of NSCLC patients with COPD, the
      extracted DNAs were deep-sequenced using next generation sequence technologies
      for somatic mutations in a maximum 72 cancer-associated genes. Logistic
      regression analysis was performed to evaluate the impact of COPD on the somatic
      mutations. RESULTS: The COPD group (n=77), including 56 GOLD 1 and 21 GOLD 2 or 3
      patients, had 58 squamous cell lung carcinoma (SCC) cases and 19 adenocarcinoma
      cases. The non-COPD group (n=120) had 53 SCC cases, 64 adenocarcinoma cases, and
      three cases with other histology. The frequency of PIK3CA mutation was
      significantly higher in the COPD group than in the non-COPD group (10.4% vs.
      1.7%, p=0.015). Meanwhile, NFE2L2 mutation was observed only in SCC cases, with
      no difference in the frequency between the two groups (17.2% vs. 17.0%). In the
      multivariate logistic regression model with consideration for COPD status, age,
      smoking dose, pathological stage, and histology, significantly more PIK3CA
      mutation was observed in the presence of COPD (odds ratio=5.31, 95% CI: 1.03
      27.29, p=0.046). CONCLUSIONS: PIK3CA mutation is a distinctive genetic feature of
      NSCLC with COPD, regardless of age, smoking dose, pathological stage, and
      histology.

PMID- 29191608
TI  - A fully digital approach to replicate functional and aesthetic parameters in
      implant-supported full-arch rehabilitation.
AB  - PURPOSE: The aim of this technical procedure was to use a fully digital technique
      (FDT) for full-arch implant support rehabilitation. The FDT was used to transfer
      the provisional restoration parameters to definitive restorations using intraoral
      scanners. METHODS: Three sets of digital impressions were obtained. Through the
      first set, standard tessellation language 1 (STL1), provisional restorations
      screwed to implants and the surrounding gingival tissue was captured. STL2
      consisted of intraoral scans of standardized scanbodies screwed to implants to
      collect 3D positioning data of implants. STL3 included the digital impression of
      provisional restoration out of the mouth in order to capture the gingival
      architecture and the peri-implant soft tissue that was not possible to transfer
      with the previous impressions. STL1, STL2, and STL3 were combined using computer
      aided design (CAD) functions into a single file, STL4. Thus, STL4 contained
      information on the 3D implant positions, soft tissue architectures, occlusal
      relationships, correct occlusal vertical dimension and aesthetic features. Using
      STL4, the master models with implant analogues were 3D printed. Computer-aided
      design and computer-aided manufacturing milled (CAD/CAM-milled) aluminium bars
      and a resin prototype were produced to test the accuracy and the functional and
      aesthetic parameters. Titanium frameworks were digitally designed using STL4,
      milled using CAD/CAM, and finalized with pink resin and resin teeth. CONCLUSION:
      The FDT provided an effective fully digital protocol to capture all information
      for provisional full-arch implant restorations using an intraoral scanner and
      transfer that information to definitive restorations.

PMID- 29191609
TI  - Accuracy of various impression materials and methods for two implant systems: An
      effect size study.
AB  - PURPOSE: An accurate impression is required for implant treatment. The aim of
      this in-vitro study was to determine the effect size of the impression
      material/method, implant system and implant angulation on impression transfer
      precision. METHODS: An upper jaw model with three BEGO and three Straumann
      implants (angulations 0 degrees , 15 degrees , 20 degrees ) in the left and right
      maxilla was used as a reference model. One polyether (Impregum Penta) and two
      polyvinyl siloxanes (Flexitime Monophase/Aquasil Ultra Monophase) were examined
      with two impression techniques (open and closed tray). A total of 60 impressions
      were made. A coordinate measurement machine was used to measure the target
      variables for 3D-shift, implant axis inclination and implant axis rotation. All
      the data were subjected to a four-way ANOVA. The effect size (partial eta-squared
      [eta2P]) was reported. RESULTS: The impression material had a significant
      influence on the 3D shift and the implant axis inclination deviation (p
      values=.000), and both factors had very large effect sizes (3D-shift
      [eta2P]=.599; implant axis inclination [eta2P]=.298). Impressions made with
      polyvinyl siloxane exhibited the highest transfer precision. When the angulation
      of the implants was larger, more deviations occurred for the implant axis
      rotational deviation. The implant systems and impression methods showed partially
      significant variations (p-values=.001-.639) but only very small effect sizes
      (eta2P=.001-.031). CONCLUSIONS: The impression material had the greatest effect
      size on accuracy in terms of the 3D shift and the implant axis inclination. For
      multiunit restorations with disparallel implants, polyvinyl siloxane materials
      should be considered. In addition, the effect size of a multivariate
      investigation should be reported.

PMID- 29191610
TI  - Incidence and prevention of infective endocarditis and bacteraemia after
      transcatheter aortic valve implantation in a French university hospital: a
      retrospective study.
AB  - Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI)
      is a rare but severe complication. Among 326 patients who underwent TAVI at
      Grenoble Alpes University Hospital, six (1.8%) cases of IE and 11 (3.4%) cases of
      bacteraemia were identified. No cases of IE were linked to the intervention; one
      was due to Staphylococcus aureus despite a screening and targeted decolonization
      strategy. This underscores the need for randomized studies to evaluate the
      benefit and cost-effectiveness of this policy.

PMID- 29191611
TI  - Activation of peroxymonosulfate using drinking water treatment residuals for the
      degradation of atrazine.
AB  - Drinking water treatment residuals (WTRs) are safe byproducts of water treatment
      plants containing iron. This work studies the degradation of atrazine (ATZ) by
      WTR-catalyzed peroxymonosulfate (PMS) in aqueous solutions. Factors that affect
      the catalytic performance (the PMS concentration, catalyst dose, initial solution
      pH, reaction temperature and water matrix species) were investigated. The results
      show that the catalytic degradation efficiency of ATZ increases with the increase
      in PMS concentration and temperature, whereas a higher content of WTRs results in
      lower removal efficiency because of the quenching effect and negative effect of
      high pH. For an initial solution pH of 3 and 5, 94.1% and 87.4% of ATZ
      degradation can be achieved within 6h, whereas the value is only 26% for pH of 7.
      The production of sulfate radicals (SO4-) and hydroxyl radicals (OH) was
      confirmed by classic radical quenching and electron spin resonance (ESR) tests.
      Based on the GC-MS and LC-MS results, the main degradation pathways of ATZ may
      contain dealkylation, dechlorination-hydroxylation, and alkyl chain oxidation
      processes. In addition to the ATZ removal ability, the WTRs/PMS system can
      simultaneously remove phosphorus. This article provides a new idea for wastewater
      treatment and usage of WTRs as a resource.

PMID- 29191612
TI  - In vivo activity of fluconazole/tetracycline combinations in Galleria mellonella
      with resistant Candida albicans infection.
AB  - OBJECTIVES: Treatment of azole-resistant Candida albicans infections continues to
      pose significant challenges. With limited options of licensed agents, drug
      combinations may be a practical treatment alternative. In our previous studies,
      the combinations minocycline/fluconazole (MINO/FLC) and doxycycline/fluconazole
      (DOXY/FLC) shown synergistic effects in vitro. It is necessary to explore their
      appropriate dosage, potential toxicity and in vivo efficacy. METHODS: The
      Galleria mellonella infection model was employed to study the in vivo efficacy of
      MINO/FLC and DOXY/FLC by survival analysis, quantification of C. albicans fungal
      burden and histological studies. RESULTS: The survival rates of G. mellonella
      larvae infected with lethal doses of resistant C. albicans CA10 increased
      significantly when treated with the drug combinations compared with FLC treatment
      alone, and the fungal burden was reduced by almost four-fold. The
      histopathological study showed that fewer infected areas in larvae were observed
      and the destructive degree was less when larvae were exposed to the drug
      combinations. CONCLUSIONS: These findings suggest that combination of a
      tetracycline antibiotic (MINO or DOXY) with FLC has antifungal activity against
      azole-resistant C. albicans in vivo. This is in agreement with several previous
      in vitro studies and provides preliminary in vivo evidence that such a
      combination might be useful therapeutically.

PMID- 29191613
TI  - Abnormal biventricular performance in asymptomatic adolescents late after
      repaired Tetralogy of Fallot: Combined two-dimensional speckle tracking and three
      dimensional echocardiography study.
AB  - BACKGROUND: The aim of this prospective study was to assess biventricular
      performance in asymptomatic adolescents with repaired tetralogy of Fallot (TOF)
      using 2D speckle tracking and real time 3D echocardiography simultaneously.
      METHODS: We studied 31 patients with repaired TOF (M/F: 22/9, age: 16.1 +/- 6.1
      yrs) who had history of cardiac surgery with mean follow-up duration of 12.8
      years, and 32 age- and sex-matched normal individuals (M/F: 23/9, age: 16.6 +/-
      5.1 yrs). All subjects underwent speckle tracking and 3D echocardiography,
      electrocardiogram, treadmill, and blood sampling for measurement of brain
      natriuretic peptide (BNP). RESULTS: Compared to the control group, the TOF group
      had higher BNP level (31.8 +/- 21.4 vs 14.1 +/- 12.4 pg/ml, p < 0.01), lower peak
      oxygen consumption (8.4 +/- 1.7 vs 9.9 +/- 1.6 ml/kg/min, p < 0.05), and longer
      QRS duration (126 +/- 30 vs 82 +/- 9 ms, p < 0.01). Patients with repaired TOF
      had significantly impaired right ventricle (RV) global and all six regional
      longitudinal strain and strain rate than normal controls. Left ventricle (LV)
      global and mainly apical regional longitudinal strain and strain rate were
      reduced in patients with repaired TOF. There was a significant correlation of
      global longitudinal strain (r = 0.456, p = 0.01) and global time to peak
      longitudinal strain (r = 0.484, p < 0.01) between LV and RV in patients with
      repaired TOF. In terms of 3D echo cardiographic volume data, patients with
      repaired TOF had lower LV stroke volume index (p < 0.05), but higher RV end
      diastolic volume index (p < 0.01), RV end systolic volume index (p < 0.01), RV
      stroke volume index (p < 0.01), and pulmonary regurgitation fraction (p < 0.01)
      than normal controls. CONCLUSION: Our results suggest asymptomatic adolescents
      with repaired TOF had abnormal biventricular myocardial performance, as
      demonstrated by combined 2D speckle-tracking and 3D echocardiography. The
      implications of these findings for management of adolescents late after repaired
      TOF remain to be determined.

PMID- 29191614
TI  - Accuracy of a Cone-Beam CT Virtual Parenchymal Perfusion Algorithm for Liver
      Cancer Targeting during Intra-arterial Therapy.
AB  - PURPOSE: To evaluate accuracy of virtual parenchymal perfusion (VPP) algorithm
      developed for targeting liver cancer during intra-arterial therapy (IAT) using
      cone-beam CT guidance. MATERIALS AND METHODS: VPP was retrospectively applied to
      15 patients who underwent IAT for liver cancer. Virtual territory (VT) was
      estimated after positioning a virtual injection point on nonselective dual-phase
      (DP) cone-beam CT images acquired during hepatic arteriography at the same
      position chosen for selective treatment. Targeted territory (TT) was used as the
      gold standard and was defined by parenchymal phase enhancement of selective DP
      cone-beam CT performed before treatment start. Qualitative evaluation of anatomic
      conformity between VT and TT was performed using a 3-rank scale (poor,
      acceptable, excellent) by 3 double-blinded readers. VT and TT were also
      quantitatively compared using spatial overlap-based (Dice similarity coefficient
      [DSC], sensitivity, and positive predictive value), distance-based (mean surface
      distance [MSD]), and volume-based (absolute volume error and correlation between
      pairwise volumes) metrics. Interreader agreement was evaluated for the 2
      evaluation methods. RESULTS: Eighteen DP cone-beam CT scans were performed.
      Qualitative evaluation showed excellent overlap between VT and TT in 88.9%-94.4%,
      depending on the readers. DSC was 0.78 +/- 0.1, sensitivity was 80%, positive
      predictive value was 83%, and MSD was 5.1 mm +/- 2.4. Absolute volume error was
      15%, and R2 Pearson correlation factor was 0.99. Interreader agreement was good
      for both qualitative and quantitative evaluations. CONCLUSIONS: VPP algorithm is
      accurate and reliable in identification of liver arterial territories during IAT
      using cone-beam CT guidance.

PMID- 29191615
TI  - Percutaneous Mitral Valve Technology: What Is on the Horizon?
AB  - Mitral valve disease is common, with mitral regurgitation (MR) being the most
      frequent pathology. The etiology of MR is diverse, but, if left untreated, MR
      results in left ventricular (LV) volume overload, leading to remodeling, dilation
      of the LV, pulmonary hypertension, heart failure, and death. Mitral regurgitation
      is a high-risk diagnosis, yet a minority of symptomatic patients are referred for
      discussion of surgical treatment options. Percutaneous repair options are under
      development to address this clinical need and emphasize correction of the
      underlying anatomical pathology to restore mitral valve coaptation. Transcatheter
      mitral valve replacement is in the early stages of development and may prove safe
      and effective in certain patient populations. Investigational devices are
      challenging our current thinking about the management of mitral valve disease,
      and it will be the task of the multidisciplinary Heart Team to determine the
      right device for the right pathology.

PMID- 29191616
TI  - Lung Cancer Surgery in the Elderly: Age Is Just a Number.

PMID- 29191617
TI  - Pulmonary Sclerosing Pneumocytoma: Did Lightening Just Strike Twice?

PMID- 29191618
TI  - Is "As Good" Good Enough?

PMID- 29191619
TI  - Lung Cancer Screening in the Post-National Lung Screening Trial Era: Applying
      Screening in the Real World.
AB  - The National Lung Screening Trial established a survival benefit for lung cancer
      screening using low-dose computed tomography. In the wake of this trial several
      international bodies now recommend lung cancer screening. However, three main
      questions remain unanswered: Who is the optimal population for screening? How
      often should they be screened? For how long should screening be continued? We
      examine the results of the available randomized trials to address these
      questions.

PMID- 29191620
TI  - Genetic Alterations in Primary Acral Melanoma and Acral Melanocytic Nevus in
      Korea: Common Mutated Genes Show Distinct Cytomorphological Features.
AB  - Acral melanoma occurring on the palms, soles, and nails is the most common
      subtype of cutaneous melanoma in Asians. Genetic alterations in acral melanoma
      and acral melanocytic nevus are not well known. We performed next-generation
      sequencing and evaluated the correlations between genetic information and the
      clinicopathologic characteristics from 85 Korean patients with acral melanocytic
      neoplasms. Of the 64 patients with acral melanoma, most had lesions at the T2
      stage or higher, and the heel was the most common anatomical site of melanoma (n
      = 34 [53.1%]). The five most common mutations were BRAF (22 [34.4%]), NRAS (14,
      [21.9%]), NF1 (11, [17.2%]), GNAQ (12, [17.2%]), and KIT (7, [10.9%]). In the 21
      acral melanocytic nevi, those five gene mutations were also common. Copy number
      variations were also frequently detected in 75% of acral melanomas and 47.6% of
      acral melanocytic nevi, and amplification was more common than deletion in both
      lesions. BRAF mutation was associated with round epithelioid cells and NRAS and
      NF1 mutations with bizarre cells. NF1 and GNAQ mutations showed elongated and
      spindle cells with prominent dendrites in acral melanomas. KIT mutations were
      common in amelanotic acral melanoma. This study suggests that common mutated
      genes are associated with distinct cytomorphological features in acral
      melanocytic lesions.

PMID- 29191621
TI  - Propionibacterium acnes Induces Autophagy in Keratinocytes: Involvement of
      Multiple Mechanisms.
AB  - Propionibacterium acnes is a dominant member of the cutaneous microbiota. Herein,
      we evaluate the effects of different P. acnes strains and propionic acid on
      autophagy in keratinocytes. Our results showed that P. acnes strain 889 altered
      the architecture of the mitochondrial network; elevated the levels of microtubule
      associated protein 1 light chain 3B-II, Beclin-1, and phospho-5'-adenosine
      monophosphate-activated protein kinase alpha; stimulated autophagic flux;
      facilitated intracellular redistribution of microtubule-associated protein 1
      light chain 3B; increased average number of autophagosomes per cell; and enhanced
      development of acidic vesicular organelles in the HPV-KER cell line. Propionic
      acid increased the level of phospho-5'-adenosine-monophosphate-activated protein
      kinase alpha, enhanced lipidation of microtubule-associated protein 1 light chain
      3B, stimulated autophagic flux, and facilitated translocation of microtubule
      associated protein 1 light chain 3B into autophagosomes in HPV-KER cells. P.
      acnes strains 889 and 6609 and heat-killed strain 889 also stimulated
      autophagosome formation in primary keratinocytes to varying degrees. These
      results indicate that cell wall components and secreted propionic acid metabolite
      of P. acnes evoke mitochondrial damage successively, thereby triggering 5'
      adenosine-monophosphate-activated protein kinase-associated activation of
      autophagy, which in turn facilitates the removal of dysfunctional mitochondria
      and promotes survival of keratinocytes. Thus, we suggest that low-level
      colonization of hair follicles with noninvasive P. acnes strains, by triggering a
      local increase in autophagic activity, might exert a profound effect on several
      physiological processes responsible for the maintenance of skin tissue
      homeostasis.

PMID- 29191622
TI  - Interplay between behavior, morphology and physiology supports lepidophagy in the
      catfish Pachypterus khavalchor (Siluriformes: Horabagridae).
AB  - The present study demonstrates the scale-eating behavior of a siluroid catfish,
      Pachypterus khavalchor, and the role of its oral structure and bacterial
      endosymbionts in shaping this lepidophagous habit. Scale-eating behavior in P.
      khavalchor was studied using a series of behavioral experiments. P. khavalchor
      was found to feed only on the scales of live fish and never of dead fish, even
      after 72h of starvation. It was nocturnal in habit and attacked all species that
      were used as prey. Attacking behavior showed extensive chasing of prey species
      followed by a powerful random strike at the flank or close to the caudal region
      in posterior oblique position. After a strike, P. khavalchor was found to
      immediately turn back and pick up the falling dislodged scales. SEM analysis of
      oral structures of P. khavalchor revealed three different types of teeth arranged
      in specific order on the upper jaw, lower jaw and pharyngeal region that could
      facilitate their lepidophagous habit. Teeth of upper and lower jaws are likely to
      help in dislodging the scales and pharyngeal teeth may help to engulf the scales.
      Gut microflora analysis and enzyme assay revealed two isolates, namely Bacillus
      pumilus and Bacillus licheniformis, which were positive for chitinase production.
      These two isolates were found to be capable of producing chitinase indicating
      that they are likely to be involved in the digestion of chitin-rich scales in the
      host fish gut. An in vitro scale degradation assay further strengthens the
      results since both isolates were found to be efficient in chitinase production
      and degradation of scales.

PMID- 29191623
TI  - Diversity out of simplicity: interaction behavior of land planarians with co
      occurring invertebrates.
AB  - Land planarians have a simple anatomy and simple behavioral repertoire in
      relation to most bilaterian animals, which makes them adequate for the study of
      biological processes. In this study, we investigate the behavior of land
      planarians during interaction events with other invertebrates found in the same
      environment. We observed 16 different behavioral units, including seven different
      capture behaviors and three different prey ingestion behaviors. The capture
      behavior varied from very simple, such as simply covering the prey with the body,
      to more complex ones, including two forms of tube formation that are described
      for the first time. In general, the capture behaviors were similar among
      different predators but different for different prey. Similarly, prey ingestion
      type was more related to prey type than to predator species, with small soft prey
      being swallowed without fragmentation, large prey being crushed, and prey with a
      hard skeleton being perforated. Considering that land planarians face limitations
      due to their lack of efficient ways to retain water, thus being highly dependent
      on a moist environment, the set of behaviors shown by them in this study was
      considerably rich, especially concerning strategies to capture prey.

PMID- 29191624
TI  - Phosphate Kinetic Models in Hemodialysis: A Systematic Review.
AB  - BACKGROUND: Understanding phosphate kinetics in dialysis patients is important
      for the prevention of hyperphosphatemia and related complications. One approach
      to gain new insights into phosphate behavior is physiologic modeling. Various
      models that describe and quantify intra- and/or interdialytic phosphate kinetics
      have been proposed, but there is a dearth of comprehensive comparisons of the
      available models. The objective of this analysis was to provide a systematic
      review of existing published models of phosphate metabolism in the setting of
      maintenance hemodialysis therapy. STUDY DESIGN: Systematic review. SETTING &
      POPULATION: Hemodialysis patients. SELECTION CRITERIA FOR STUDIES: Studies
      published in peer-reviewed journals in English about phosphate kinetic modeling
      in the setting of hemodialysis therapy. PREDICTOR: Modeling equations from
      specific reviewed studies. OUTCOMES: Changes in plasma phosphate or serum
      phosphate concentrations. RESULTS: Of 1,964 nonduplicate studies evaluated, 11
      were included, comprising 9 different phosphate models with 1-, 2-, 3-, or 4
      compartment assumptions. Between 2 and 11 model parameters were included in the
      models studied. Quality scores of the studies using the Newcastle-Ottawa Scale
      ranged from 2 to 11 (scale, 0-14). 2 studies were considered low quality, 6 were
      considered medium quality, and 3 were considered high quality. LIMITATIONS: Only
      English-language studies were included. CONCLUSIONS: Many parameters known to
      influence phosphate balance are not included in existing phosphate models that do
      not fully reflect the physiology of phosphate metabolism in the setting of
      hemodialysis. Moreover, models have not been sufficiently validated for their use
      as a tool to simulate phosphate kinetics in hemodialysis therapy.

PMID- 29191625
TI  - Impact of Diabetes Mellitus on the Association of Vascular Disease Before
      Transplantation With Long-term Transplant and Patient Outcomes After Kidney
      Transplantation: A Population Cohort Study.
AB  - BACKGROUND: Advances in kidney transplantation have led to considerable
      improvements in short-term transplant and patient outcomes, but there are few
      data regarding long-term transplant outcomes in patients with vascular comorbid
      conditions. This study examined the association of vascular disease before
      transplantation with transplant and patient survival after transplantation and
      evaluated whether this association was modified by diabetes. STUDY DESIGN: All
      deceased donor kidney transplant recipients recorded in the Australia and New
      Zealand Dialysis and Transplant Registry (ANZDATA) for 1990 to 2012. PREDICTOR:
      Vascular disease burden. OUTCOMES: All-cause mortality and overall transplant
      loss. Potential interactions between diabetes and vascular disease for mortality
      and transplant loss were assessed using 2-way interaction terms. RESULTS: Of
      7,128 recipients with 58,120 patient-years of follow-up, 854 (12.0%) and 263
      (3.7%) had vascular diseases at 1 and 2 or more sites, respectively. Overall
      survival for recipients without vascular disease 15 years after transplantation
      was 65% compared with 35% and 22% among recipients with vascular disease at 1 and
      2 or more sites, respectively (P<0.001). Compared with recipients without
      vascular disease, adjusted HRs for mortality and transplant loss were 1.75 (95%
      CI, 1.39-2.20; P<0.001) and 1.61 (95% CI, 1.30-1.99; P<0.001), respectively, for
      recipients with 2 or more vascular diseases. Among recipients without diabetes
      but with 2 or more vascular diseases, adjusted HRs for mortality and transplant
      loss were 2.10 (95% CI, 1.56-2.82; P<0.001) and 1.84 (95% CI, 1.39-2.42;
      P<0.001), respectively, compared with those without vascular disease. Similar
      associations were not observed for recipients with diabetes mellitus (P for
      interaction < 0.001). LIMITATIONS: Selection bias and unmeasured residual
      confounders, such as the severity/extent of comorbid conditions likely to be
      present. CONCLUSIONS: The impact of vascular disease on long-term outcomes was
      modified by the presence of diabetes, whereby excess risks for death and
      transplant loss are more apparent in recipients without diabetes.

PMID- 29191626
TI  - To support and to be supported. A qualitative study of peer support centres in
      cancer care in Norway.
AB  - OBJECTIVE: To explore what peer supporters, patients and their relatives want and
      gain from peer support in cancer care. METHODS: Focus group interviews with peer
      supporters, and in-depth interviews with peer supporters, patients and relatives
      (N=38) and observations of daily activities in a Vardesenter ("Cairn Centre").
      RESULTS: Peer supporters helped cancer patients and relatives with coping in and
      outside the hospital in several ways: (1) conveying hope and providing ways to
      cope in situations where despair would often be prevalent, thus protecting
      against unhealthy stress; (2) being someone who had the same experiences of
      disease and treatment, and thus providing a framework for positive social
      comparisons; and (3) to be an important supplement to family and health care
      providers. To be working as a peer supporter was also found to be positive and
      important for the peer supporters themselves. CONCLUSION: The peer support
      program represented a valuable supplement to informal support from family and
      friends and healthcare providers, and gave the peer supporters a new role as
      "professionally unprofessional". PRACTICE IMPLICATIONS: Organised peer support
      represents a feasible intervention to promote coping for cancer survivors.

PMID- 29191627
TI  - Scarlet fever makes a comeback.

PMID- 29191628
TI  - Resurgence of scarlet fever in England, 2014-16: a population-based surveillance
      study.
AB  - BACKGROUND: After decades of decreasing scarlet fever incidence, a dramatic
      increase was seen in England beginning in 2014. Investigations were launched to
      assess clinical and epidemiological patterns and identify potential causes.
      METHODS: In this population-based surveillance study, we analysed statutory
      scarlet fever notifications held by Public Health England from 1911 to 2016 in
      England and Wales to identify periods of sudden escalation of scarlet fever.
      Characteristics of cases and outbreaks in England including frequency of
      complications and hospital admissions were assessed and compared with the pre
      upsurge period. Isolates from throat swabs were obtained and were emm typed.
      FINDINGS: Data were retrieved for our analysis between Jan 1, 1911, and Dec 31,
      2016. Population rates of scarlet fever increased by a factor of three between
      2013 and 2014 from 8.2 to 27.2 per 100 000 (rate ratio [RR] 3.34, 95% CI 3.23
      3.45; p<0.0001); further increases were observed in 2015 (30.6 per 100 000) and
      in 2016 (33.2 per 100 000), which reached the highest number of cases (19 206)
      and rate of scarlet fever notifcation since 1967. The median age of cases in 2014
      was 4 years (IQR 3-7) with an incidence of 186 per 100 000 children under age 10
      years. All parts of England saw an increase in incidence, with 620 outbreaks
      reported in 2016. Hospital admissions for scarlet fever increased by 97% between
      2013 and 2016; one in 40 cases were admitted for management of the condition or
      potential complications. Analysis of strains (n=303) identified a diversity of
      emm types with emm3 (43%), emm12 (15%), emm1 (11%), and emm4 (9%) being the most
      common. Longitudinal analysis identified 4-yearly periodicity in population
      incidence of scarlet fever but of consistently lower magnitude than the current
      escalation. INTERPRETATION: England is experiencing an unprecedented rise in
      scarlet fever with the highest incidence for nearly 50 years. Reasons for this
      escalation are unclear and identifying these remains a public health priority.
      FUNDING: None.

PMID- 29191629
TI  - Effects of Delta(9)-tetrahydrocannabinol (THC) on human amniotic epithelial cell
      proliferation and migration.
AB  - BACKGROUND: The deleterious effects of cannabis consumption for fertility and
      pregnancy outcome are recognized for years. The main psychoactive molecule of
      cannabis, Delta(9)-tetrahydrocannabinol (THC) is able to cross the placenta
      barrier and cause alterations in fetal growth, low birth weight and preterm
      labor. However, the effects of THC on the human placenta amnion are still
      unknown. METHODS: The distributions of CB1R and CB2R in human amnion tissues were
      observed by immunohistochemistry (IHC). Human amniotic epithelial cell
      proliferation and migration in response to THC treatment were measured by MTS and
      transwell assays, respectively. The PCR array was performed to study the key
      regulators involved in the cell migration. The protein levels of CB1R, CB2R in
      amnion tissues and MMP2, MMP9 in cells were detected by western blotting. Small
      interfering RNAs (siRNAs) were used to knockdown MMP2 and MMP9 in WISH cells.
      RESULTS: Our results indicated that both CB1R and CB2R primarily identified in
      the epithelial layer of human placental amnion tissue. The CB1R expression in the
      amnion tissue was higher in the preterm group than normal control. High-dose of
      THC (30uM, but not 20 and 10uM) significantly inhibited (p<0.01) human amniotic
      epithelial cell lines (WISH) proliferation. Meanwhile, THC at both 10uM and 20uM
      (p<0.05) significantly suppressed cells migration in both WISH and primary human
      amniotic epithelial cells. The PCR array data and siRNA experiments demonstrated
      that MMP2/9 were tightly involved in the regulation of THC-inhibited cell
      migration in WISH cells. CONCLUSION: These results suggested that THC inhibited
      the migration of human amniotic epithelial cell through the regulation of MMP2
      and MMP9, which in turn altered the development of the amnion during the
      gestation and partially resulted in preterm labor and other adverse pregnancy
      outcomes.

PMID- 29191630
TI  - Efficacy and safety of bivalirudin in coronary artery disease patients with mild
      to moderate chronic kidney disease: Meta-analysis.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) have elevated bleeding and
      ischemic outcomes. We aim to assess the short- and long-term efficacy and safety
      of bivalirudin compared to heparin plus glycoprotein IIb/IIIa inhibitors (GPIs)
      in coronary artery disease (CAD) patients with CKD. METHODS: Randomized trials
      were searched in PubMed, Cochrane, and Embase databases up to January 2017. Among
      the trials retrieved, efficacy endpoints were defined as mortality, myocardial
      infarction (MI), repeat revascularization, stent thrombosis, and major adverse
      cardiac events (MACEs). Safety endpoints were reported as non-coronary artery
      bypass grafting (CABG) related major bleeding and thrombolysis in myocardial
      infarction (TIMI) major bleeding. Risk ratio (RR) and 95% confidence interval
      (CI) were calculated for each outcome using a fixed effect model. RESULTS: Five
      studies with a total of 3796 patients were included. In short-term follow up (30
      days), bivalirudin significantly reduced non-CABG related major bleeding
      (p=0.0004) and TIMI major bleeding (p=0.007) compared to heparin plus GPIs. No
      significant differences were observed in rates of mortality, MI, repeat
      revascularization, stent thrombosis, and MACEs between the two groups in short-
      and long-term follow up (6 months to 3 years). In patients with ST elevated
      myocardial infarction (STEMI) with concurrent CKD, the decreased non-CABG related
      major bleeding (p=0.04) without increasing ischemic events was also observed
      after short-term follow up. CONCLUSIONS: (1) Bivalirudin is safer than and as
      effective as heparin plus GPIs in CAD patients with CKD. (2) Impaired renal
      function does not affect the safety benefits of bivalirudin. (3) Similar efficacy
      profiles were identified between the two groups after both short- and long-term
      follow up in the CAD patients with CKD.

PMID- 29191632
TI  - Recent controversy regarding the accuracy of CT-FFR. The truth is out there.

PMID- 29191631
TI  - [Clinical problems in medical mycology: Problem number 52].
AB  - The case of a 60 year old woman with hemoptysis and a thin-walled cavitary lesion
      at the upper lobe of the right lung is presented. The woman presented at the
      Mycology Unit of the Muniz Hospital in Buenos Aires City 3 months after the
      beginning of her clinical manifestations. A hyaline micelial fungus with chlamido
      arthroconidias was isolated from the bronchoalveolar lavage. Immunodiffusion and
      counter-immnunoelectrophoresis with coccidioidin and histoplasmin rendered
      positive results against both antigents, and skin tests with coccidioidin and
      histoplasmin were also positive with strong reactions. The isolated fungus was
      identified as Coccidioides posadasii at the National Microbiology Institute
      Carlos Malbran, by means of a molecular technique. The patient was treated with
      itraconazole by oral route at a daily dose of 200mg with good clinical response,
      but due to the persistence of the lung cavity, a surgical removal of the upper
      lobe of the right lung had to be scheduled.

PMID- 29191633
TI  - Sensitivity of intervertebral joint forces to center of rotation location and
      trends along its migration path.
AB  - Translational vertebral motion during functional tasks manifests itself in
      dynamic loci for center of rotation (COR). A shift of COR affects moment arms of
      muscles and ligaments; consequently, muscle and joint forces are altered. Based
      on posture- and level-specific trends of COR migration revealed by in vivo
      dynamic radiography during functional activities, it was postulated that the
      instantaneous COR location for a particular joint is optimized in order to
      minimize the joint reaction forces. A musculoskeletal multi-body model was
      employed to investigate the hypotheses that (1) a posterior COR in upright
      standing and (2) an anterior COR in forward flexed posture leads to optimized
      lumbar joint loads. Moreover, it was hypothesized that (3) lower lumbar levels
      benefit from a more superiorly located COR. The COR in the model was varied from
      its initial position in posterior-anterior and inferior-superior direction up to
      +/-6 mm in steps of 2 mm. Movement from upright standing to 45 degrees  forward
      bending and backwards was simulated for all configurations. Joint reaction forces
      were computed at levels L2L3 to L5S1. Results clearly confirmed hypotheses (1)
      and (2) and provided evidence for the validity of hypothesis (3), hence offering
      a biomechanical rationale behind the migration paths of CORs observed during
      functional flexion/extension movement. Average sensitivity of joint force
      magnitudes to an anterior shift of COR was +6 N/mm in upright and -21 N/mm in 30
      degrees  forward flexed posture, while sensitivity to a superior shift in upright
      standing was +7 N/mm and -8N/mm in 30 degrees  flexion. The relation between COR
      loci and joint loading in upright and flexed postures could be mainly attributed
      to altered muscle moment arms and consequences on muscle exertion. These findings
      are considered relevant for the interpretation of COR migration data, the
      development of numerical models, and could have an implication on clinical
      diagnosis and treatment or the development of spinal implants.

PMID- 29191634
TI  - A mathematical analysis to address the 6 degree-of-freedom segmental power
      imbalance.
AB  - Segmental power is used in human movement analyses to indicate the source and net
      rate of energy transfer between the rigid bodies of biomechanical models.
      Segmental power calculations are performed using segment endpoint dynamics
      (kinetic method). A theoretically equivalent method is to measure the rate of
      change in a segment's mechanical energy state (kinematic method). However, these
      two methods have not produced experimentally equivalent results for segments
      proximal to the foot, with the difference in methods deemed the "power
      imbalance." In a 6 degree-of-freedom model, segments move independently,
      resulting in relative segment endpoint displacement and non-equivalent segment
      endpoint velocities at a joint. In the kinetic method, a segment's distal end
      translational velocity may be defined either at the anatomical end of the segment
      or at the location of the joint center (defined here as the proximal end of the
      adjacent distal segment). Our mathematical derivations revealed the power
      imbalance between the kinetic method using the anatomical definition and the
      kinematic method can be explained by power due to relative segment endpoint
      displacement. In this study, we tested this analytical prediction through
      experimental gait data from nine healthy subjects walking at a typical speed. The
      average absolute segmental power imbalance was reduced from 0.023 to 0.046 W/kg
      using the anatomical definition to <=0.001 W/kg using the joint center definition
      in the kinetic method (95.56-98.39% reduction). Power due to relative segment
      endpoint displacement in segmental power analyses is substantial and should be
      considered in analyzing energetic flow into and between segments.

PMID- 29191636
TI  - [The imperative of generating more integrative and comprehensive approaches to
      address the therapeutic challenge of multi-morbility].

PMID- 29191635
TI  - O-POSSUM score predicts morbidity and mortality in patients undergoing hip
      fracture surgery.
AB  - PURPOSE: The aim of this study is to evaluate the O-POSSUM score capacity to
      predict the morbidity and mortality of patients undergoing hip fracture surgery.
      MATERIAL AND METHODS: We retrospectively reviewed the clinical records of
      patients older than 65years old, operated on for hip fractures between January
      2012 and December 2013. Of 229 patients, the mean age was 82.3years and 170 were
      women. We collected comorbidities, type of surgery, and expected morbidity and
      mortality O-POSSUM values. RESULTS: After a minimum follow up of one year, 38
      deaths were reported and 77 patients had complications. The expected mortality
      according to the O-POSSUM was 35 patients and expected morbidity 132. CONCLUSION:
      By comparing the observed results with those predicted, the O-POSSUM scale is
      reliable in predicting mortality and overestimates morbidity.

PMID- 29191637
TI  - Spontaneous development of hepatosteatosis in perilipin-1 null mice with adipose
      tissue dysfunction.
AB  - Fatty liver features triglyceride accumulation in hepatocytes and often occurs
      with obesity and lipodystrophy in humans. Here, we investigated the mechanism of
      maladaptive hepatosteatosis with adipose-tissue dysfunction. Perilipin 1 (Plin1)
      did not exist in hepatocytes but was expressed exclusively in adipocytes as a
      dual modulator for regulating two principal adipose-tissue functions,
      triglyceride storage and breakdown. Plin1-/- mice showed decreased fat storage
      but increased lipolysis and efflux of fatty acids from adipose tissue, and
      hepatosteatosis spontaneously developed without altered circulating inflammatory
      adipocytokine levels. Plin1-/- adipose dysfunction impaired insulin sensitivity
      and hepatic glucose metabolism, which might inhibit gluconeogenesis to produce
      more intermediates for hepatic lipid synthesis. Indeed, the livers of Plin1-/-
      mice exhibited upregulated mRNA and protein expression of key enzymes and
      transcriptional factors for the uptake and transport of fatty acids and for de
      novo synthesis of triglycerides, but the expression of key enzymes and
      transcriptional factors for fatty-acid oxidation was downregulated. Biochemical
      assays in Plin1-/- mice confirmed increased fatty acid synthase activity but
      decreased activity of mitochondrial carnitine palmitoyltransferase 1 and [3H]
      palmitate oxidation in the liver. We concluded that dysregulation of two
      principal functions, adipose storage and hydrolysis, had deleterious consequences
      on the hepatic lipid metabolism and thereby caused maladaptive hepatosteatosis.
      This mouse model might mimic and explain the pathogenesis of hepatosteatosis
      occurring in two typical disorders of adipose tissue dysfunction, obesity and
      lipodystrophy, particularly in lipodystrophic patients with Plin1 mutation.

PMID- 29191639
TI  - Population-based Analysis of Treatment Toxicity Among Men With Castration
      resistant Prostate Cancer: A Phase IV Study.
AB  - OBJECTIVE: To assess the toxicity and effectiveness of contemporary metastatic
      castrate-resistant prostate cancer (mCRPC) treatments at a population level,
      among all patients in Ontario particularly treated with newer agents, including
      abiraterone, enzalutamide, docetaxel, and cabazitaxel. METHODS: We performed a
      population-based, retrospective cohort study of 2439 men aged >=65 years treated
      for mCRPC with abiraterone, enzalutamide, docetaxel, or cabazitaxel from 2003 to
      2015 in Ontario, Canada. Our primary outcome was treatment-related toxicity,
      defined as hospitalizations and emergency room (ER) visits during mCRPC
      treatment. Based on toxicity profiles identified during phase III trials, we
      further identified specific treatment-related toxicity. We calculated hazard
      ratios (HRs) using multivariable Cox proportional hazards models with time
      varying exposures. RESULTS: Abiraterone and enzalutamide exposure were not
      associated with any-cause (P = .19 and .52, respectively) or treatment-related (P
      = .45 and .64, respectively) toxicities. In contrast, docetaxel exposure was
      associated with an increased risk of any-cause (HR 1.29, 95% confidence interval
      [CI] 1.15-1.44) and treatment-related (HR 1.52, 95% CI 1.33-1.74) toxicities.
      Cabazitaxel exposure was associated with a significant risk of treatment-related
      toxicity (HR 5.94, 95% CI 1.87-18.92) but not any-cause toxicity (HR 2.37, 95% CI
      0.59-9.63). CONCLUSION: Among patients with mCRPC, we failed to show any
      increased risk of hospitalizations and ER visits for treatment-related
      complications for abiraterone or enzalutamide. In contrast, treatment with
      intravenous chemotherapeutic agents was associated with an increased risk of
      hospitalizations and ER visits to manage these complications.

PMID- 29191638
TI  - Cystathionine gamma-lyase/hydrogen sulfide system is essential for adipogenesis
      and fat mass accumulation in mice.
AB  - Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter
      analogous to nitric oxide and carbon monoxide. Cystathionine gamma-lyase (CSE)
      derived H2S is implicated in the regulation of insulin resistance and glucose
      metabolism, but the involvement of CSE/H2S system in energy homeostasis and fat
      mass has not been extensively explored. In this study, a potential functional
      role of the CSE/H2S system in in vitro adipocyte differentiation and in vivo
      adipogenesis and the underlying mechanism was investigated. CSE expression and
      H2S production were increased during adipocyte differentiation, and that the
      pattern of CSE mRNA expression was similar to that of CCAAT/enhancer-binding
      protein (C/EBP) beta and delta, two key regulators for adipogenesis. C/EBPbeta
      and gamma bind to the CCAAT box in CSE promoter and stimulate CSE gene
      transcription. H2S induced PPARgamma transactivation activity by S-sulfhydrating
      all the cysteine residues in the DNA binding domain and stimulated adipogenesis.
      High fat diet-induced fat mass was lost in CSE deficient mice, and exogenously
      applied H2S promoted fat mass accumulation in fruit flies. In conclusion, CSE/H2S
      system is essential for adipogenesis and fat mass accumulation through
      enhancement of PPARgamma function in adipocytes. This study suggests that the
      CSE/H2S system is involved in the pathogenesis of obesity in mice.

PMID- 29191640
TI  - Incidence of Visible Hematuria Among Antithrombotic Agents: A Systematic Review
      of Over 175,000 Patients.
AB  - OBJECTIVE: To determine the probability of visible hematuria with antithrombotic
      agents and to evaluate association of urologic etiology in antithrombotic-related
      hematuria. METHODS: Preferred Reporting Items in Systematic Reviews and Meta
      Analyses guidelines were followed to conduct a systematic review using search
      engines PUBMED and SCOPUS with the terms "(hematuria) OR (haematuria) OR urinary
      bleeding)) AND ((anticoagulants) OR anticoagulation) OR noac) OR novel
      anticoagulants) OR antiplatelet) OR dabigatran) OR rivaroxaban) OR apixaban) OR
      warfarin) OR aspirin) OR heparin) OR dipyridamole)." Raw data were used to
      perform a pooled analysis. Chi-square and logistic regression analysis were used
      for statistical analyses. RESULTS: Twenty-two studies describing 175,114 patients
      met inclusion criteria. Odds ratio of hematuria with warfarin to rivoraxaban was
      33 and warfarin to dabigatran was 16. The odds ratio of hematuria for oral
      anticoagulant (26.7%) to prophylactic parenteral anticoagulant (1.1%) agents was
      9.6. Antiplatelet agents are 76 times less likely to cause hematuria compared to
      anticoagulants. Odds of hematuria with aspirin were 6.7 times the odds with
      clopidogrel and 3.5 times the odds with ticagrelor. Dabigatran was 198 times more
      likely to cause major hematuria compared to warfarin, whereas clopidogrel is 1.2
      times more likely to cause major hematuria compared to aspirin. Urologic
      pathology was identified in 44% (234/532) of cases, malignancy in 24%.
      CONCLUSION: Warfarin use poses the greatest risk for hematuria but is unlikely to
      cause major hematuria, whereas novel antithrombotic agents are more commonly
      associated with major hematuria. This review further characterizes the risk
      profile of antithrombotic agents and associated hematuria to equip clinicians
      with knowledge to choose an appropriate antithrombotic agent in patients with
      high-risk hematuria.

PMID- 29191641
TI  - Vena Cavoscopy in the Assessment of Intraluminal Vena Caval Tumor Involvement.
AB  - OBJECTIVE: To improve confirmation of complete tumor thrombus removal in advanced
      malignancy, we report on our experience using intraoperative vena cavoscopy using
      a flexible cystoscope to confirm complete thrombus resection. Patients with renal
      cell carcinoma or testicular cancer associated with inferior vena caval tumor
      involvement benefit from surgical resection of the primary tumor and the tumor
      thrombus. Intraoperative assessment of the vena cava represents a technical
      challenge, particularly when the thrombus is friable and involves the hepatic
      veins, or there is caudal extension of thrombus toward the bifurcation. MATERIAL
      AND METHODS: From 2006 to 2014, 36 patients underwent tumor thrombectomy and vena
      cavoscopy. When residual caval thrombus was suspected, a flexible cystoscope was
      inserted into the vena cava for direct visual inspection of the caval lumen.
      Perioperative outcomes including residual tumor, changes in management, and
      postoperative complications were analyzed. RESULTS: All patients underwent
      endoscopy of the caval lumen without complications. Eight of 36 (22%) patients
      were found to have residual tumor thrombus visualized during cavoscopy. Five of
      these patients had evidence of residual mass and caval invasion within the caval
      lumen that ultimately resulted in cavectomy. Two patients had residual tumor
      thrombus that was bluntly removed. One patient was found to have significant
      involvement of the hepatic veins. CONCLUSION: Vena cavoscopy using a flexible
      cystoscope is a practical technique that may be utilized intraoperatively to
      ensure clearance of residual thrombus burden within the inferior vena cava and to
      assess for caval invasion.

PMID- 29191642
TI  - Combined Partial Penectomy With Bilateral Robotic Inguinal Lymphadenectomy Using
      Near-infrared Fluorescence Guidance.
AB  - OBJECTIVE: To describe our novel technique for performing a combined partial
      penectomy and bilateral robotic inguinal lymphadenectomy using intraoperative
      near-infrared (NIR) fluorescence guidance with indocyanine green (ICG) and the
      DaVinci Firefly camera system. METHODS: A 58-year-old man presented status post
      recent excisional biopsy of a 2-cm lesion on the left coronal aspect of the glans
      penis. Pathology revealed "invasive squamous cell carcinoma of the penis with
      multifocal positive margins." His examination was suspicious for cT2 primary and
      his inguinal nodes were cN0. He was counseled to undergo partial penectomy with
      possible combined vs staged bilateral robotic inguinal lymphadenectomy.
      Preoperative computed tomography scan was negative for pathologic
      lymphadenopathy. Before incision, 5 mL of ICG was injected subcutaneously beneath
      the tumor. Bilateral thigh pockets were then developed simultaneously and a
      right, then left robotic modified inguinal lymphadenectomy was performed using
      NIR fluorescence guidance via the DaVinci Firefly camera. A partial penectomy was
      then performed in the standard fashion. RESULTS: The combined procedure was
      performed successfully without complication. Total operative time was 379 minutes
      and total robotic console time was 95 minutes for the right and 58 minutes to the
      left. Estimated blood loss on the right and left were 15 and 25 mL, respectively.
      A total of 24 lymph nodes were retrieved. CONCLUSION: This video demonstrates a
      safe and feasible approach for combined partial penectomy and bilateral inguinal
      lymphadenectomy with NIR guidance using ICG and the DaVinci Firefly camera
      system. The combined robotic approach has minimal morbidity and avoids the need
      for a staged procedure. Furthermore, use of NIR guidance with ICG during robotic
      inguinal lymphadenectomy is feasible and may help identify sentinel lymph nodes
      and improve the quality of dissection. Further studies are needed to confirm the
      utility of NIR guidance for robotic sentinel lymph node dissection.

PMID- 29191643
TI  - Incidence of Stress Urinary Incontinence After Posterior Urethroplasty for
      Radiation-induced Urethral Strictures.
AB  - OBJECTIVE: To identify the frequency of de novo stress urinary incontinence (SUI)
      after posterior excision and primary anastomotic (EPA) urethroplasty in patients
      with radiation-induced urethral strictures (RIUS) and compare with patients with
      pelvic fracture urethral injuries (PFUIs). MATERIALS AND METHODS: A retrospective
      review was conducted among patients who underwent successful posterior EPA
      urethroplasty between 2008 and 2016 for RIUS from prostate cancer or PFUI from
      blunt trauma. Only patients with an intact bladder neck on imaging were included.
      SUI was defined by patient-reported outcomes and daily pad use. RESULTS:
      Inclusion criteria were met by 36 patients with RIUS and 33 patients with PFUI.
      Among the RIUS cohort, mean follow-up was 18 months, mean stricture length was
      2.5 cm, and surgical dissection extended to the prostatic urethra in 67% (n =
      24). The overall frequency of de novo SUI among patients with RIUS was 33% (n =
      12), of which 75% (9 of 12) had prostatic urethral involvement. Two patients with
      RIUS (17%, n = 12) proceeded with artificial urinary sphincter (AUS) placement,
      whereas the remaining 10 patients required pads. SUI after urethroplasty in
      patients with PFUI was less common (12%, n = 4) and the prostatic urethra was
      involved in only 3% (n = 1) of all patients with PFUI. One patient with PFUI
      underwent AUS placement, whereas the remaining 3 patients did not require pads.
      CONCLUSION: Among RIUS patients with an intact bladder neck, SUI impacts one
      third of patients. Subsequent AUS placement is uncommon. Prostatic urethral
      involvement increases risk of SUI. SUI is less common among patients with PFUI,
      likely related to a more limited involvement of the proximal bulbomembranous
      urethra and lack of radiation.

PMID- 29191644
TI  - Preclinical assessment of utility of M6S for multimodal acute and chronic pain
      treatment in diabetic neuropathy.
AB  - AIMS: Previous reports from our laboratory have established that morphine-6-O
      sulfate (M6S) is a mixed MU/delta opioid receptor (OR) agonist and a potential
      improved alternative to morphine for treatment of chronic multimodal pain in non
      diabetic rats. This study extends the antinociceptive effects of M6S and morphine
      in STZ-induced diabetic rats. MATERIALS AND METHODS: Effects of morphine and M6S
      were studied across a range of pain modalities, using hot plate threshold (HPT),
      pinprick sensitivity threshold (PST) and paw pressure threshold (PPT) tests. KEY
      FINDINGS: Acutely, M6S was 3- to 5-fold more potent and 2- to 3-fold more
      efficacious than morphine in HPT and PST tests. No differences in analgesic drug
      potency/efficacy were detected in the PPT test. After 7-9days of chronic
      treatment, tolerance developed to the antinociceptive effects of morphine, but
      not to M6S, in all three pain tests. Furthermore, morphine-tolerant rats were not
      cross-tolerant to M6S. The selective delta-OR antagonist, naltrindole, blocked
      M6S-induced antinociception by 62+/-3% in the HPT test, 93+/-5% in the PST test,
      and 30+/-17% in the PPT test when examined acutely. SIGNIFICANCE: These studies
      provide additional confirmation for the mixed MU/delta activity of M6S and
      demonstrate potential improved clinical utility for dual MU/delta agonists
      relative to morphine in treatment of diabetic neuropathy across multiple pain
      domains.

PMID- 29191645
TI  - Protective effects of estrogen against cardiovascular disease mediated via
      oxidative stress in the brain.
AB  - During their reproductive years women produce significant levels of estrogens,
      predominantly in the form of estradiol, that are thought to play an important
      role in cardioprotection. Mechanisms underlying this action include both estrogen
      mediated changes in gene expression, and post-transcriptional activation of
      protein signaling cascades in the heart and in neural centers controlling
      cardiovascular function, in particular, in the brainstem. There, specific
      neurons, especially those of the bulbar region play an important role in the
      neuronal control of the cardiovascular system because they control the outflow of
      sympathetic activity and parasympathetic activity as well as the reception of
      chemical and mechanical signals. In the present review, we discuss how estrogens
      exert their cardioprotective effect in part by modulating the actions of
      internally generated products of cellular oxidation such as reactive oxygen
      species (ROS) in brain stem neurons. The significance of this review is in
      integrating the literature of oxidative damage in the brain with the literature
      of neuroprotection by estrogen in order to better understand both the benefits
      and limitations of using this hormone to prevent cardiovascular disease.

PMID- 29191646
TI  - [Thrombotic and haemorrhagic complications in patients with cerebral aneurysms
      treated by endovascular approach and their association with the use of
      antiplatelet agents: Descriptive evaluation].
AB  - OBJECTIVE: The protocol for optimal antiplatelet therapy to prevent thrombotic
      complications following brain aneurysm embolisation is not clear. Our objective
      is to describe the characteristics of patients presenting with thrombotic or
      haemorrhagic complications secondary to endovascular treatment. METHODS: A cross
      sectional descriptive study was performed, which included all patients that
      required endovascular treatment for brain aneurysm at San Ignacio University
      Hospital from November 2007 to January 2016. Thrombotic and haemorrhagic
      complications over six months of follow-up were assessed, considering the
      premedication regimen with antiplatelet agents, location, size of the aneurysm
      and embolisation technique performed. RESULTS: 122 patients were evaluated, on
      whom 130 procedures were performed for endovascular treatment of brain aneurysms.
      Thrombotic complications were more frequent in patients who did not receive
      premedication (25%) compared to those who did receive an antiplatelet treatment
      regimen (standard dose 3.87% or loading dose 8.70%), and this difference was
      statistically significant (P=.043). CONCLUSIONS: Thromboembolic events are the
      most common complication of brain aneurysm embolisation. Both our study and the
      literature suggest that the use of dual antiplatelet therapy with aspirin and
      clopidogrel lowers the rate of symptomatic thromboembolic complications,
      regardless of the administration protocol.

PMID- 29191647
TI  - Defining and identifying concepts of medication literacy: An international
      perspective.
AB  - BACKGROUND: Multiple concepts to define health literacy in the context of
      medication use exist, such as medication literacy, pharmacotherapy literacy,
      pharmacy health literacy; however, no studies have looked at consensus among
      experts internationally. METHOD: A Delphi process was used to achieve consensus
      on the statements about medication literacy. Experts for the Delphi were selected
      from a review of the literature and suggestions from an international survey
      conducted with members of the International Pharmaceutical Federation on
      medication literacy. The preliminary Delphi questionnaire was built using the
      statements about medication literacy found in the scientific literature.
      Responses and comments were analyzed using a pre-established method and
      communicated to the experts after each round of Delphi. Statements with an
      agreement of at least 80% were accepted and used to develop a definition of
      medication literacy. RESULTS: The Delphi process started with 21 experts and
      included 4 rounds. Overall, 30 statements regarding medication literacy were
      accepted and divided into 4 clusters representing: (1) type of information
      necessary for optimal and safe use of medication, (2) skills and abilities, (3)
      format of information, and (4) outcomes. These statements were used to propose 2
      different definitions of medication literacy. One of the definitions was
      preferred by 75% of the expert panel, which provided further comments for
      improvements. Of the 11 experts who answered the final questionnaire, nine
      strongly agreed with the refined definition. CONCLUSION: Medication literacy is
      the degree to which individuals can obtain, comprehend, communicate, calculate
      and process patient-specific information about their medications to make informed
      medication and health decisions in order to safely and effectively use their
      medications, regardless of the mode by which the content is delivered (e.g.
      written, oral and visual). Future studies should focus on how this definition can
      be operationalized to support the role that pharmacists and other healthcare
      providers.

PMID- 29191648
TI  - Ventilation Strategy During Cardiopulmonary Bypass: A Moving Target.

PMID- 29191649
TI  - Multilevel Thoracic Paravertebral Block Using Ropivacaine With/Without
      Dexmedetomidine in Video-Assisted Thoracoscopic Surgery.
AB  - OBJECTIVES: Thoracic paravertebral block (TPVB) is reported to have advantages in
      postoperative pain management in unilateral thoracic surgeries. Previous studies
      have demonstrated that dexmedetomidine could be used as an adjuvant to local
      anesthetics, with the aim of prolonging the duration of neural blockade. However,
      little is known about whether such a combination could improve the quality of
      postoperative analgesia compared with local anesthetic only when TPVB is used for
      patients undergoing video-assisted thoracoscopic surgery (VATS). DESIGN: A
      prospective, randomized, controlled study. SETTING: Single-center university
      hospital. PARTICIPANTS: The study included 60 patients undergoing VATS under
      general anesthesia. INTERVENTIONS: The patients were allocated randomly into the
      following 2 groups: 0.375% ropivacaine, 20 mL only (group R, n = 30), and 0.375%
      ropivacaine, 20 mL plus 1 MUg/kg of dexmedetomidine (group RD, n = 30). At the
      end of surgery, TPVB guided using ultrasound was performed at 4 points-T4-5, T5
      6, T6-7, and T7-8-of the surgical side; 5 mL of solution were injected at each
      point. Postoperatively, the intravenous nonsteroidal anti-inflammatory drug
      flurbiprofen was used as part of multimodal analgesia. MEASUREMENTS AND MAIN
      RESULTS: Pain scores at rest and during coughing were evaluated by a blinded
      observer in the postanesthesia care unit postoperatively at 1, 2, 4, 8, 12, 24,
      36, and 48 hours, and the dermatomal levels of sensory blockade, postoperative
      requirements for rescue analgesia, adverse events, and patient satisfaction also
      were recorded. There was a significant reduction in postoperative pain scores at
      rest starting from the postoperative 8th hour until the 48th hour and during
      coughing starting at the postoperative 4th hour until the 48th hour in the group
      RD compared with those in group R (p = 0.043). The dermatomal levels of sensory
      blockade were comparable in the 2 groups. Patient satisfaction after surgery was
      significantly higher in the group RD than in group R (p < 0.001). Total
      consumption of the intravenous rescue analgesic morphine and adverse events were
      not significantly different between the 2 groups. CONCLUSIONS: Compared with
      ropivacaine only, the addition of dexmedetomidine, 1 MUg/kg, to local anesthetic
      for multilevel TPVB in patients undergoing VATS prolonged the duration of
      postoperative analgesia and improved patient satisfaction without serious side
      effects when combined with postoperative intravenous nonsteroidal anti
      inflammatory drug administration.

PMID- 29191650
TI  - Cortical Language Areas and Plasticity in Pediatric Patients With Epilepsy: A
      Review.
AB  - Chronic injury to the brain from seizure activity is associated with decreased
      language skills in pediatric patients, as measured on neuropsychological tests
      for language function and academic achievement. This makes the study of language
      in patients with epilepsy clinically necessary. Functional magnetic resonance
      imaging and direct electrical cortical stimulation have been used to evaluate
      aspects of cortical language processing in healthy adults and in adults with
      epilepsy or other neurological insults. Results of these studies help to locate
      cortical language areas that are involved with modality-specific language
      processing (visual naming, auditory naming, sentence-completion, and repetition)
      and the neuroplasticity of language areas in the setting of neurological injury
      and reorganization. A better understanding of language processing contributes to
      a more efficient and efficacious electrical cortical stimulation mapping of
      language areas for patients with intractable epilepsy who are undergoing
      preresection evaluation. Most of the current literature on localization and
      reorganization of cortical language areas in the setting of epilepsy concerns the
      adult patient population, whereas the literature on pediatric patients is
      substantially lacking in comparison. This article reviews the conclusions drawn
      thus far from Wada, magnetoencephalography, functional magnetic resonance
      imaging, and electrical cortical stimulation language studies on types of
      language reorganization seen in pediatric patients with intractable temporal lobe
      epilepsy and the clinical factors associated with reorganization, and proposes
      future directions of research to further the academic and clinical understanding
      of language processing in pediatric patients.

PMID- 29191652
TI  - Effect of erythropoietin production induced by hypoxia on autophagy in HepG2
      cells.
AB  - The induction of hypoxia inducible factor (HIF) and autophagy are important
      cellular responses to hypoxia. The production of erythropoietin (EPO) regulated
      by HIF is increased by hypoxia and participates in cell protection in various
      organs and tissues. Signal Transducers and Activator of Transcription 3 (STAT3)
      is a regulatory factor that is common to autophagy induction and EPO-EPO receptor
      signaling. In this study, we analyzed the promotion of EPO production and
      autophagy, and the participation of STAT3, in HepG2 cells under hypoxia.
      Treatment with EPO siRNA (si-EPO) significantly increased autophagy induction by
      hypoxia, while treatment with recombinant EPO inhibited the effect of si-EPO.
      NSC74859, an inhibitor of the phosphorylation of STAT3, increased autophagy
      induction to the same extent as si-EPO treatment. Even when 3-Methyladenine, an
      inhibitor of autophagy, was added, the increase of EPO mRNA expression due to
      hypoxia was not affected. Hypoxia-induced EPO restrained autophagy induction
      through the EPO receptor and phosphorylation of STAT3. Because cell viability
      with treatment of si-EPO under hypoxia did not increase over the control, our
      results suggested that EPO produced by hypoxia prevented excess autophagy
      induction.

PMID- 29191651
TI  - Molecular Interactions of a DNA Modifying Enzyme APOBEC3F Catalytic Domain with a
      Single-Stranded DNA.
AB  - The single-stranded DNA (ssDNA) cytidine deaminase APOBEC3F (A3F) deaminates
      cytosine (C) to uracil (U) and is a known restriction factor of HIV-1. Its C
      terminal catalytic domain (CD2) alone is capable of binding single-stranded
      nucleic acids and is important for deamination. However, little is known about
      how the CD2 interacts with ssDNA. Here we report a crystal structure of A3F-CD2
      in complex with a 10-nucleotide ssDNA composed of poly-thymine, which reveals a
      novel positively charged nucleic acid binding site distal to the active center
      that plays a key role in substrate DNA binding and catalytic activity. Lysine and
      tyrosine residues within this binding site interact with the ssDNA, and mutating
      these residues dramatically impairs both ssDNA binding and catalytic activity.
      This binding site is not conserved in APOBEC3G (A3G), which may explain
      differences in ssDNA-binding characteristics between A3F-CD2 and A3G-CD2. In
      addition, we observed an alternative Zn-coordination conformation around the
      active center. These findings reveal the structural relationships between nucleic
      acid interactions and catalytic activity of A3F.

PMID- 29191653
TI  - Distorted antibody repertoire developed in the absence of pre-B cell receptor
      formation.
AB  - The pre-B cell receptor (pre-BCR), consisting of the MU heavy chain (MUHC) and
      the surrogate light chain (SLC, Vpre-B and lambda5), plays important roles during
      B cell development. The formation of the pre-BCR, which enables the nascent
      immunoglobulin HC to associate with the SLC, is considered a prerequisite for B
      cell development. However, a significant number of peripheral mature (leaky) B
      cells exist in SLC-deficient mice. These leaky B cells develop in the absence of
      pre-BCR and do not undergo the pre-BCR checkpoint. The antibody repertoires of
      leaky B cells thus reflect the absence of pre-BCR function. To investigate how
      the absence of the pre-BCR is circumvented by these leaky-B cells and examine the
      effect of the pre-BCR checkpoint on the antibody system, we analyzed the antibody
      repertoires of lambda5-deficient (lambda5-/-) mice using next-generation
      sequencing. In lambda5-/- mice, spleen B cells displayed different patterns of
      VDJ-usage, relative to those in wild-type (WT) mice. Moreover, leaky B cells were
      neither derived from unusual B2 cells, characterized by particular LC gene
      rearrangements in the absence of pre-BCR signaling, nor from B1 cells,
      originating from different B cell progenitors. Analysis of the CDR-H3 amino acid
      sequences of MU-chain repertoires revealed that certain bone marrow B cells with
      particular CDR-H3 profiles undergo clonal expansion in lambda5-/- mice. Part of
      these CDR-H3s contain arginine(s) in the middle of the CDR-H3 loop in lambda5-/-
      mice, whereas few arginine(s) exist in this middle loop in WT CDR-H3s in the
      absence of clonal expansion. This CDR-H3 feature in lambda5-/- mice presumably
      reflects the role of the pre-BCR in autoantibody regulation, since arginine(s)
      are often found in the antigen-binding site of autoantibodies. Here, we present a
      unique viewpoint on the role of pre-BCR, by assessing the whole antibody
      repertoire formed in SLC-deficient mice.

PMID- 29191654
TI  - Differential mGluR5 expression in response to the same stress causes individually
      adapted hippocampal network activity.
AB  - Individual differences in stress vulnerability and resilience have been observed
      even within a single cohort of inbred rats or mice. Stress phenotypes are
      typically quantified as changes in the behavior of experimental animals, which is
      the outcome of altered electrical activity of the brain network. Although mGluR5
      is associated with individual vulnerability to stress and can act as a sensitive
      biomarker of stress adaptation, our understanding of mGluR5-dependent
      modifications to neural network activities in vivo remains limited. Here, we
      examined individual rats for changes in hippocampal mGluR5 expression induced by
      restraint stress and found that these changes cause accompanying changes in
      hippocampal electroencephalography (EEG) activity. We found six days of restraint
      stress caused variable changes in hippocampal mGluR5 expression, ranging from
      20.9% to 210.7% of the control group. The low mGluR5 protein group (LE) showed
      increased methylation of the mGluR5 CpG island, reduced mGluR5 mRNA levels, and
      unaltered basal EEG theta spectral power between stress day 1 and 6. In contrast,
      the high mGluR5 protein group (HE) showed reduced methylation of CpG sites,
      increased mGluR5 mRNA expression, and reduced basal theta spectral power on
      stress day 6. We also found that injection of lentiviruses expressing mGluR5
      specific shRNAs into the hippocampus rescued this reduction in baseline theta
      power in HE rats. These data suggest a causal relationship between individual
      differences in the changes in hippocampal mGluR5 expression induced by repetitive
      restraint stress and the accompanying changes in ensemble neural activity in the
      hippocampus.

PMID- 29191656
TI  - Overexpression of microRNA-26a protects against deficient beta-cell function via
      targeting phosphatase with tensin homology in mouse models of type 2 diabetes.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) increased rapidly in the world.
      The development of beta-cell dysfunction is the quintessential defects in T2DM
      patients However, the pathogenesis of beta-cell dysfunction is still unclear.
      MicroRNAs are short non-coding RNAs and has been reported to be involved in
      pathogenesis of beta-cell dysfunction and T2DM. Here, we investigated the
      mechanisms by which miR-26a regulate beta-cell function and insulin signaling
      pathway in high fat diet (HFD) fed and db/db T2DM mice model. The expression of
      miR-26a was down-regulated dramatically in the serum and islets of both HFD and
      db/db mice model. miR-26a overexpression protected against HFD-induced diabetes
      and maintained prolonged normoglycemic time in HFD fed mice. Overexpression of
      miR-26a improved beta-cell dysfunction in T2DM mice. Further, we identified that
      PTEN is a direct target gene of miR-26a. Overexpression of miR-26a significantly
      inhibited the luciferase activity of hPTEN 3'-UTR, while the effect of miR-26a
      disappeared when the miR-26a potential binding site within the PTEN 3'-UTR was
      mutated. Overexpression of miR-26a reduced both the mRNA and protein levels of
      PTEN in vitro and in vivo. We also found that miR-26a overexpression increased
      the expression of p-Akt and p-FoxO-1, while the effect of miR-26a was blocked by
      PTEN overexpression. In conclusion, our data indicated that miR-26a potentially
      contributes to the beta-cell dysfunction in T2DM, and miR-26a may be a new
      therapeutic strategy against T2DM.

PMID- 29191655
TI  - Q482H mutation of procaspase-8 in acute myeloid leukemia abolishes caspase-8
      mediated apoptosis by impairing procaspase-8 dimerization.
AB  - INTRODUCTION: Certain procaspase-8 mutations are reported to be associated with
      the progression and prognosis of multiple tumors. However, it remains unclear
      whether the poor chemotherapy response and frequent relapse after complete
      remission of patients with acute myeloid leukemia (AML) is also related to
      procaspase-8 abnormalities. METHODS: Polymerase chain reaction (PCR)
      amplification and Sanger sequencing of the procaspase-8 gene (CASP8) were
      performed. Apoptotic rates were analyzed with Annexin V-FITC staining in cells
      expressing wild-type (WT) procaspase-8, the Q482H or C360S mutant, or control
      vector after treatment with or without tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). Western blot analysis was performed to detect activation
      of procaspase-8 and downstream apoptotic signaling pathway components in those
      cells. The Co-immunoprecipitation (Co-IP) assays were performed to detect
      interaction between WT and mutant procaspase-8 proteins. RESULTS: AML patients
      carrying the Q482H mutation were likely to develop chemotherapy resistance.
      Similar to C360S, The Q482H mutation abolished caspase-8-mediated apoptotic
      signaling and inhibited TRAIL-induced apoptosis. The Q482H mutation impaired
      procaspase-8 dimerization, thus preventing the self-activation of procaspase-8.
      CONCLUSION: The procaspase-8 Q482H mutation in AML patients abolishes caspase-8
      mediated apoptosis by impairing procaspase-8 dimerization.

PMID- 29191657
TI  - Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in
      synovial sarcoma.
AB  - The development of drug resistance in tumor cells leads to relapse and distant
      metastasis. Secreted microRNAs (miRNAs) enclosed in extracellular vesicles (EVs)
      can act as intercellular messengers. The objective of our study was to elucidate
      the role of secreted miRNAs to better understand the regulatory network
      underlying pazopanib-resistance in synovial sarcoma cells. We performed a
      comprehensive analysis of secreted miRNA abundance in pazopanib treated/untreated
      synovial sarcoma cells from four different cell lines (SYO-1, HS-SYII, 1273/99,
      and YaFuSS) using microarray technology, and discovered miR-761 in EVs as a
      potential biomarker of pazopanib-resistance in synovial sarcoma. Furthermore, we
      showed that miR-761 putatively targeted three proteins, thyroid hormone receptor
      interactor 6 (TRIP6), lamin A/C (LMNA), and NAD-dependent protein deacetylase
      sirtuin-3 (SIRT3). Knockdown of any of these proteins was shown in previous
      studies to confer increased resistance to chemotherapeutic agents. Our findings
      provide new insight into the potential role of miR-761, an EV-secreted miRNA from
      synovial sarcoma cells, making it a potential candidate for use in sarcoma
      therapy in the future.

PMID- 29191659
TI  - Let's talk about sex: Behaviors, experience and health care utilization in young
      women with CF.

PMID- 29191660
TI  - Early experience with shared medical appointments for penile problems.
AB  - We examined the use of shared medical appointments (SMA) for educating and
      counseling children with penile problems. Forty-eight families were seen over 4
      months with 21 participating in the SMA group and 27 in the traditional group.
      Using a questionnaire to assess adequacy of education, there was no difference in
      the overall scores between groups with a mean of 6.64/7 in the SMA and 6.56/7 in
      the traditional setting. With the increasing demands on providers, an SMA offers
      a solution to caring for more patients with penile problems in an efficient
      manner without impacting family education and satisfaction.

PMID- 29191658
TI  - Identification and target-modifications of temporin-PE: A novel antimicrobial
      peptide in the defensive skin secretions of the edible frog, Pelophylax kl.
      esculentus.
AB  - A potent natural antimicrobial peptide named temporin-PE was identified and
      encoded from the skin secretions of Pelophylax kl. esculentus via "shotgun"
      cloning and LC-MS/MS fragmentation analysis. Target-modifications were carried
      out to further enhance the antimicrobial and anti-proliferative bioactivities,
      whilst decreasing the hemolytic effect. A range of bioassays demonstrated that
      replacing a proline with a tyrosine residue resulted in a loss of the bioactivity
      against Gram-negative bacteria, but dramatically improved the hemolytic and anti
      proliferative activity, indicating the FLP- motif influences the hemolytic
      activity of temporins. Moreover, the coupling of TAT to the peptide dramatically
      improved its antimicrobial activity, indicating coupling TAT to these peptides
      could be considered as a potential tool to improve their antimicrobial activity.
      Overall, we have shown that targeted modifications of this natural antimicrobial
      peptide can adjust its bioactivities to help its development as an antibiotic or
      anti-proliferative agent.

PMID- 29191661
TI  - Anterior Segment Dimensions Following Laser Iridotomy in Acute Primary Angle
      Closure and Fellow Eyes.
AB  - PURPOSE: To compare the change in anterior segment morphology after laser
      peripheral iridotomy (LPI) in acute primary angle closure (APAC) and their fellow
      eyes. DESIGN: Prospective, fellow eye-matched case series. METHODS: In this study
      42 individuals with unilateral episode of APAC were enrolled and the anterior
      segment optical coherence tomography (ASOCT) images were obtained in both eyes at
      baseline and at 6 weeks after LPI. A linear mixed-effects model was used to
      compare changes in anterior chamber and angle variables with consideration of
      laterality as the random effect and pupil diameter as the fixed effect. RESULTS:
      APAC eyes had smaller angle parameters (P = .013 for all), less central anterior
      chamber depth (cACD) (P < .001), and lower anterior chamber area (ACA) (P <
      .001), as well as greater lens vault (LV) (P = .007), compared with fellow eyes.
      LPI resulted in angle widening with a significant increase in opening distance (P
      < .01 for all) in both APAC and fellow eyes. cACD (P = .003) and ACA (P < .001)
      increased and LV (P = .002) decreased in APAC eyes. However, there was no
      significant change in cACD (P = .190) and LV (P = .430) in fellow eyes. In both
      APAC eyes and fellow eyes, iris curvature decreased after LPI (P < .001). The
      changes in angle parameters, ACA, and iris curvature were not significantly
      different between the 2 groups. CONCLUSION: In APAC eyes and their fellow eyes,
      LPI resulted in significant anterior chamber angle widening and increased
      anterior chamber area. In APAC eyes, the iris flattened, cACD deepened, and the
      lens shifted posteriorly after resolution of the attack. However, in fellow eyes,
      the increase in ACA was mainly owing to decreased iris curvature.

PMID- 29191662
TI  - Osseous and Adipocytic Differentiations in the Intraocular Lens and Vitreous.
AB  - PURPOSE: To analyze 3 unusual mesenchymal transformations within the eye: adipose
      or osseous metaplasia of the lens and adipose tissue in the vitreous cavity.
      DESIGN: Observational case series. METHODS: Reevaluation of clinicopathologic
      diagnoses and histopathologic findings in sections stained with hematoxylin
      eosin, periodic acid-Schiff (PAS) reaction, and Masson trichrome method. RESULTS:
      The 3 cases of mesenchymal transformation occurred in microphthalmic eyes with
      persistent hyperplastic primary vitreous (more recently termed persistent fetal
      vasculature). In 1 case there was total lens replacement with lamellar bone; in
      another, total replacement of the crystalline lens by adipose tissue; and in a
      third, an anomalous pocket of adipose tissue in the central vitreous. Multifocal
      remnants of the lens capsule were seen in the osseous case but were absent from
      the adipocytic cases. The vitreous adipose tissue was surrounded by an elaborate
      capillary plexus with an empty, collapsed PAS-positive lens capsule in the
      pupillary region. Anterior pigmented neuroectodermal disorganization, dysgenesis
      of angle structures, and a hypoplastic or disorganized iris were also observed in
      the 3 cases. CONCLUSIONS: After review of the literature, it appears that
      lenticular osseous replacement occurs more often than adipocytic. In addition to
      vascularization of the lens through a capsular dehiscence, other causes are
      explored, including direct epithelial-mesenchymal transformations of the lens
      epithelium or, less likely, of the disorganized adjacent neuroectoderm. The focus
      of vitreous adipose tissue may represent a transformed luxated lens extruded from
      its capsule, which was left behind in the pupillary zone.

PMID- 29191663
TI  - Impact of Single-Dose Plerixafor as an Adjunct to Granulocyte Colony-Stimulating
      Factor-Based Peripheral Blood Stem Cell Mobilization on the Graft Composition and
      Outcome for T Cell-Replete Haploidentical Peripheral Blood Stem Cell
      Transplantation with Post-Transplantation Cyclophosphamide: A Comparative Study.
AB  - We conducted a prospective study on T and natural killer (NK) cell subset
      composition of graft and transplant outcomes in T cell-replete haploidentical
      transplantation with a single dose of subcutaneous plerixafor (Px) added to
      granulocyte colony-stimulating factor (G-CSF)-based mobilization in allogeneic
      donors to collect 10 * 106/kg CD34+ hematopoietic stem cells (HSCs) at single
      apheresis. Twnety-six donors received G-CSF + Px and 25 G-CSF alone for
      mobilization. Despite significantly lower peripheral blood (PB) CD34+ HSCs on day
      4 in the G-CSF + Px group (33 [range, 6-47] cells/uL versus 81 [range, 50-168]
      cells/uL in the G-CSF group; P = .0001), PB CD34+ HSC count (median 136 versus
      139 cells/uL) on day 5 as well as that in the graft (2.7 versus 2.3 * 106/mL, P =
      .1) were comparable between the 2 groups. The total nucleated cell count was
      higher (3.4 versus 3.1 * 108/mL, P = .05), but CD4+ T cells (2.3 versus 2.7 *
      107/mL, P = .09) were lower in the G-CSF group with mobilization of regulatory T
      cells being similar. NK cells were skewed toward the CD56+/16- subset in both
      groups, varying significantly from the steady-state NK subset ratio in PB. The
      time to engraftment, incidences of acute and chronic graft-versus-host disease,
      nonrelapse mortality, and overall survival were also similar. Addition of single
      dose Px to G-CSF mobilization improves CD34 recovery and does not significantly
      alter the T and NK cell composition of the graft, including regulatory T cells,
      with no adverse impact on transplant outcomes.

PMID- 29191664
TI  - Immune Reconstitution Following Autologous Stem Cell Transplantation in Patients
      with High-Risk Neuroblastoma at the Time of Immunotherapy.
AB  - Outcomes for patients with high-risk neuroblastoma (HR-NBL) are significantly
      improved with the addition of immunotherapy (dinutuximab + cytokines) following
      autologous hematopoietic stem cell transplantation (auto-HSCT). We hypothesized
      that the immune system is not fully reconstituted at the initiation of
      immunotherapy. To test this hypothesis, we evaluated hematologic and immune
      subsets in 34 patients with HR-NBL before and after auto-HSCT. We found that
      absolute T, B, and NK cell counts at the time of immunotherapy were below normal
      in 80% of patients. Patients with residual disease at the time of transplantation
      had significantly lower absolute lymphocyte counts (ALC; P = .008), lower CD16+
      cell counts (P = .009), and an abnormal ratio of cytokine-releasing to cytotoxic
      NK cells at the time of dinutuximab treatment. In addition, the preparative
      regimen used for auto-HSCT predicted immune recovery. Finally, higher total white
      blood cell count (P = .013) and ALC (P = .013) at 3 months after completion of
      therapy were measured in patients who remained in remission compared with those
      who relapsed. Our results indicate that most patients with HR-NBL do not have
      full immune reconstitution at the time of dinutuximab treatment after auto-HSCT,
      and that immune recovery may correlate with disease-related outcomes in patients
      with high-risk disease.

PMID- 29191665
TI  - Augmenting Total Body Irradiation with a Cranial Boost before Stem Cell
      Transplantation Protects Against Post-Transplant Central Nervous System Relapse
      in Acute Lymphoblastic Leukemia.
AB  - The purpose of this study was to determine the effect of a pretransplant cranial
      boost (CB) on post-transplant central nervous system (CNS) relapse and survival
      in acute lymphoblastic leukemia (ALL) patients undergoing allogeneic
      hematopoietic stem cell transplantation (HSCT) using a total body irradiation
      (TBI)-containing preparation regimen. Two hundred thirteen ALL patients were
      treated consecutively at our institution with allogeneic HSCT. Conditioning
      included TBI (1320 cGy in 8 fractions given twice daily) and cyclophosphamide
      (120 mg/kg) with or without fludarabine (75 mg/m2). Patients were divided into 4
      groups based on history of CNS disease and whether a CB was given. Of the 160
      patients with no history of CNS disease, none received a CB (CNS-/CB-). Of the 53
      patients with prior CNS disease, 41 had not received prior cranial irradiation.
      Thirty of these 41 received a CB of 900 to 1000 cGy in 5 daily fractions
      (CNS+/CB+), whereas the other 11 did not receive a CB because of physician
      preference (CNS+/CB-). The remaining 12 patients with prior CNS involvement had
      previously received cranial irradiation and thus were not candidates for a CB
      (CNS + PriorRT). Two-year CNS relapse risk, overall survival (OS), and disease
      free survival (DFS) were calculated using Kaplan-Meier analysis. Seven patients
      experienced post-transplant CNS relapse: 4 in the CNS-/CB- group, 2 in the
      CNS+/CB- group, and 1 in the CNS + PriorRT group. None of the 30 patients who
      received a CB relapsed in the CNS. Two-year CNS relapse risk was 0% in the
      CNS+/CB+ group compared with 21% (95% CI, 0% to 45%) in the CNS+/CB- group (P =
      .03). Two-year OS and DFS did not differ between the groups. In conclusion, among
      ALL patients with prior CNS leukemia, there was a trend toward a reduced risk of
      post-transplant CNS relapse in patients who received a CB. However, the addition
      of a CB did not appear to have an impact on OS or DFS.

PMID- 29191666
TI  - Nepenthes: State of the art of an inspiring plant for biotechnologists.
AB  - Plant carnivory results from the adaptation of plants to their environment. The
      capture and digestion of preys, followed by their assimilation by the plant is a
      source of additional nutrients to overcome scarce nutrient in poor soils.
      Nepenthes are highly studied carnivorous plants and have developed a number of
      ecological traits which have attracted the attention of plant biologists.
      Multiple adaptive strategies developed by these plants make them a source of
      inspiration for many applications ranging from therapeutic treatments to
      biocontrol solution in agriculture. The outstanding tissue organization of the
      digestive pitcher can help to create new and original materials usable in
      everyday life. In this review article, we propose a state of the art of the
      latest studies carried out on these particular plants and we establish a list of
      potential tracks for their exploitation.

PMID- 29191667
TI  - Complete genome sequence of Streptomyces formicae KY5, the formicamycin producer.
AB  - Here we report the complete genome of the new species Streptomyces formicae KY5
      isolated from Tetraponera fungus growing ants. S. formicae was sequenced using
      the PacBio and 454 platforms to generate a single linear chromosome with terminal
      inverted repeats. Illumina MiSeq sequencing was used to correct base changes
      resulting from the high error rate associated with PacBio. The genome is 9.6
      Mbps, has a GC content of 71.38% and contains 8162 protein coding sequences.
      Predictive analysis shows this strain encodes at least 45 gene clusters for the
      biosynthesis of secondary metabolites, including a type 2 polyketide synthase
      encoding cluster for the antibacterial formicamycins. Streptomyces formicae KY5
      is a new, taxonomically distinct Streptomyces species and this complete genome
      sequence provides an important marker in the genus of Streptomyces.

PMID- 29191668
TI  - Non-operative management is feasible for selected blunt trauma patients with
      pericardial effusion.
AB  - BACKGROUND: Blunt pericardial effusion (BPE) in trauma patients can be suggestive
      of injuries to the heart or great vessels. Surgical exploration is the mainstay
      of management; however, the effectiveness of non-operative management in this
      patient group remains unclear. METHODS: Patients presenting with BPE in the
      trauma registry system at our level I trauma center were reviewed. Patients with
      and without cardiovascular (CVS) injury were compared to identify predictors for
      CVS injury and to understand the factors related to the requirement for surgery.
      Patients with and without CVS injury who presented with stable hemodynamics and
      initially received conservative management were also compared. RESULTS: Thirty
      patients were enrolled in the study with a mean age of 53.2 (standard deviation
      (SD) 18.0) years and a mean injury severity score (ISS) of 26.7 (SD 9.0). Eleven
      patients presented with systolic blood pressure (SBP)<100mmHg, and immediate
      surgical intervention was performed. Eight patients had evidence of CVS injury
      (73%). Nineteen patients had stable hemodynamics and initially received
      conservative treatment. Of these, twelve patients received further surgical
      interventions, and only three had evidence of CVS injury (16%, 3/19). Comparisons
      of individuals with and without CVS injury revealed that the SBP on presentation
      was higher in patients without CVS injury than in those with CVS injury (132.7
      (SD 41.3) mmHg vs. 95.6 (SD 21.1) mmHg). Clinically irrelevant differences
      between the two groups were observed for the creatine kinase (CK)-MB level, the
      troponin I level, the presence of an echocardiography tamponade sign, associated
      chest trauma and ISS. No remarkable predictors for CVS injury were found in
      hemodynamically stable patients. CONCLUSION: Non-operative management can be
      considered for patents with traumatic BPE and stable hemodynamics; however, this
      approach must be performed at an institution with adequate facilities and well
      trained staff.

PMID- 29191670
TI  - Short-term cooling increases serum angiopoietin-like 4 levels in healthy lean
      men.
AB  - BACKGROUND: Cold exposure enhances sympathetic outflow to peripheral tissues,
      thereby stimulating intracellular lipolysis in white adipose tissue and
      increasing the lipoprotein lipase-dependent uptake and combustion of triglyceride
      derived fatty acids (FAs) by brown adipose tissue. Angiopoietin-like 4 (ANGPTL4)
      inhibits lipoprotein lipase and can be regulated by cold exposure, at least in
      mice. OBJECTIVE: In the present study, we examined the effect of short-term mild
      cooling on serum ANGPTL4 levels in healthy lean men of White Caucasian and South
      Asian descent. METHODS: Healthy, lean White Caucasian (n = 12) and South Asian (n
      = 12) men were exposed to an individualized cooling protocol for 2 hours. Serum
      ANGPTL4 levels were measured before and after cooling, and its relation with
      previously measured parameters (ie, free fatty acid [FFA] levels, body fat
      percentage, and resting energy expenditure) was determined. RESULTS: Short-term
      cooling increased ANGPTL4 levels (+17%, P < .001). Thermoneutral ANGPTL4 levels
      positively correlated with FFA levels (R2 = 0.250, P < .05) and body fat
      percentage (R2 = 0.338, P < .05). Furthermore, ANGPTL4 negatively correlated with
      resting energy expenditure (R2 = 0.235, P < .05). The relative increase in
      ANGPTL4 levels was higher in White Caucasians compared with South Asians (25 +/-
      4 vs 9 +/- 4%, P < .05). CONCLUSION: Short-term cooling increases ANGPTL4 levels
      in healthy lean men. We anticipate that FFA liberated from white adipose tissue
      during cooling increases ANGPTL4 to limit uptake of triglyceride-derived FA by
      this tissue.

PMID- 29191669
TI  - Incidence and factors associated with development of heterotopic ossification
      after damage control laparotomy.
AB  - INTRODUCTION: The incidence of heterotopic ossification (HO) following damage
      control laparotomy (DCL) is unknown. Abdominal wall reconstruction may prove more
      challenging in patients with HO. This study examines the incidence and factors
      associated with HO in patients with an open abdomen following DCL. METHODS: A
      retrospective review of all patients with an open abdomen after DCL at a level 1
      trauma centre from 2009 to 2015 was conducted. Demographics and peri-operative
      outcomes of patients with and without HO were compared. Univariate and
      multivariable binary logistic regression models were used to determine the
      association of peri-operative factors with the development of HO. RESULTS: 68
      patients were included, of which 36 (53%) developed HO. On univariate analysis,
      development of HO was significantly associated with hollow viscus injury (OR,
      3.89; CI 1.42-10.7), greater number of abdominal surgeries prior to definitive
      closure (OR, 1.84; CI, 1.10-3.05), non-fascial closure (OR, 4.33; CI, 1.44-13.1)
      and higher peak ALP (OR 1.01; CI, 1.00-1.02). The presence of a hollow viscus
      injury remained an independent predictor of HO on multivariable analysis after
      adjusting for covariates (OR, 3.77; CI, 1.22-11.6). CONCLUSION: Heterotopic
      ossification develops in a high proportion of trauma patients following damage
      control laparotomy, particularly in the presence of hollow viscus injury. Its
      impact on delayed abdominal wall reconstruction and the efficacy of prophylaxis
      strategies merit further investigation.

PMID- 29191671
TI  - Erectile Dysfunction and Lower Urinary Tract Symptoms.
AB  - CONTEXT: Lower urinary tract symptoms (LUTSs) and erectile dysfunction (ED) are
      substantial health concerns with a significant impact on the overall male quality
      of life. OBJECTIVE: To evaluate the available evidence of the association between
      LUTSs and ED in patients with benign prostatic hyperplasia (BPH), and discuss
      possible clinical implications for the management of LUTS/BPH. EVIDENCE
      ACQUISITION: A systematic review of the existing literature published between
      1997 and June 2017 and available in the Medline, Scopus, and Web of Science
      databases was conducted using both the Medical Subject Heading (MeSH) and free
      text protocols. The MeSH search was conducted by combining the following terms:
      "lower urinary tract symptoms," "LUTS," "benign prostatic hyperplasia," "BPH,"
      "erectile dysfunction," "sexual dysfunction," "BPE," and "benign prostatic
      enlargement." The Preferred Reporting Items for Systematic Reviews and Meta
      Analysis guidelines were followed. EVIDENCE SYNTHESIS: Several community-based
      studies in different geographical areas have provided strong evidence of an age
      independent association between LUTSs and ED. Several biological mechanisms have
      been proposed to explain this association, but further research is required to
      better understand the molecular pathways involved. It is necessary to evaluate
      the possible impact of the metabolic syndrome treatment on LUTS/ED management.
      Considering the possible relationship between LUTSs and ED, their impact on the
      quality of life, and the possible adverse effects associated with LUTS medical
      treatment, clinicians should always evaluate ED in patients with LUTSs and take
      the opportunity to evaluate patients reporting ED for LUTSs. CONCLUSIONS: Data
      from the peer-reviewed literature suggest the existence of an association between
      LUTS/BPH and ED, although their casual relationship has not been established yet.
      Emerging data also suggest that pathophysiological mechanisms involved in the
      metabolic syndrome are key factors in both disorders. Considering the
      association, it is also recommended that men presenting with LUTSs or ED should
      be evaluated for both disorders. A better understanding of the molecular pathways
      behind this association may also help identify new possible targets and develop
      novel therapeutic approaches to manage LUTSs and ED. PATIENT SUMMARY: In this
      manuscript, we report on all the available evidence linking erectile dysfunction
      and lower urinary tract symptoms. Our findings suggest the existence of a strong
      relationship between these two conditions. On the basis of these findings, we
      recommend that clinicians always explore both conditions in male patients
      presenting with either of symptoms.

PMID- 29191672
TI  - The increasing epidemic of hand, foot, and mouth disease caused by coxsackievirus
      A6, Guangdong, China, 2017.

PMID- 29191673
TI  - Automated tracing of helical assemblies from electron cryo-micrographs.
AB  - Structure determination of helical specimens commonly requires datasets from
      thousands of micrographs often obtained by automated cryo-EM data acquisition.
      Interactive tracing of helical assemblies from such a number of micrographs is
      labor-intense and time-consuming. Here, we introduce an automated tracing tool
      MicHelixTrace that precisely locates helix traces from micrographs of rigid as
      well as very flexible helical assemblies with small numbers of false positives.
      The computer program is fast and has low computational requirements. In addition
      to helix coordinates required for a subsequent helical reconstruction work-flow,
      we determine the persistence length of the polymer ensemble. This information
      provides a useful measure to characterize mechanical properties of helical
      assemblies and to evaluate the potential for high-resolution structure
      determination.

PMID- 29191674
TI  - Discussion.

PMID- 29191675
TI  - Single-stage laparoscopic management of choledocholithiasis: An analysis after
      implementation of a mastery learning resident curriculum.
AB  - BACKGROUND: Laparoscopic common bile duct exploration is an underutilized
      treatment for choledocholithiasis. We sought to evaluate the impact of a
      simulation-based mastery-learning curriculum for surgical residents on
      laparoscopic common bile duct exploration utilization and to compare outcomes for
      patients treated with laparoscopic common bile duct exploration versus endoscopic
      retrograde cholangiopancreatography (ERCP). METHODS: The number of laparoscopic
      common bile duct explorations performed before and after curriculum
      implementation was reviewed and outcomes were compared between patients with
      choledocholithiasis managed with laparoscopic common bile duct exploration and
      endoscopic retrograde cholangiopancreatography. Based on cost savings from
      increased utilization of laparoscopic common bile duct exploration, the annual
      return on investment associated with the curriculum was calculated. RESULTS:
      Twenty-two residents completed the curriculum. In the pre-curriculum period, an
      average of 1.7 laparoscopic common bile duct explorations was performed yearly,
      which increased to 8.4 cases per year after curriculum implementation (P < .05).
      Identified were 155 patients with choledocholithiasis: 31 underwent laparoscopic
      common bile duct exploration plus laparoscopic cholecystectomy and 124 underwent
      endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy.
      The laparoscopic common bile duct exploration and laparoscopic cholecystectomy
      group had a reduced duration of stay (2.5 +/- 1.8 days versus 4.3 +/- 2.2 days, P
      < .0001) and costs ($12,987 +/- $3,286 versus $15,022 +/- $4,613, P = .01)
      compared with endoscopic retrograde cholangiopancreatography and laparoscopic
      cholecystectomy. Rates of readmission and reoperation were equivalent between
      groups. Cost savings were more than $38,000, resulting in a 3.8 to 1 return on
      investment from curriculum implementation. CONCLUSION: A simulation-based mastery
      learning curriculum increased institutional utilization of laparoscopic common
      bile duct exploration and adoption of the curriculum resulted in positive return
      on investment.

PMID- 29191676
TI  - Does anatomic resection improve the postoperative outcomes of solitary
      hepatocellular carcinomas located on the liver surface?
AB  - BACKGROUND: It is unclear whether anatomic resection achieves better outcomes
      than nonanatomic resection in patients with hepatocellular carcinoma. This study
      aimed to compare the outcomes of anatomic resection and nonanatomic resection for
      hepatocellular carcinoma located on the liver surface via one-to-one propensity
      score-matching analysis. METHODS: Data from all consecutive patients who
      underwent liver resection for primary solitary hepatocellular carcinoma at Nara
      Medical University Hospital, Japan, January 2007- December 2015 were retrieved.
      Superficial hepatocellular carcinomas were defined as hepatocellular carcinoma
      that extended to a depth of < 3 cm from the liver surface and measured < 5 cm in
      diameter. The prognoses of the patients with superficial hepatocellular carcinoma
      who underwent anatomic resection and nonanatomic resection were compared.
      RESULTS: In this study 23 patients with superficial hepatocellular carcinoma
      underwent anatomic resection and 70 patients who underwent nonanatomic resection.
      The recurrence-free survival rate of the patients who underwent anatomic
      resection was better than that of the patients who underwent nonanatomic
      resection (P = .006), while no such difference was observed for nonsuperficial
      hepatocellular carcinoma. After the propensity score-matching procedure, the
      resected liver volume and operation time were the only background or clinical
      characteristics to exhibit significant differences between the anatomic resection
      (n = 20) and nonanatomic resection groups (n = 20). The recurrence-free survivial
      rate of the patients who underwent anatomic resection was significantly than that
      of the patients that underwent nonanatomic resections (P = .030), but overall
      survival did not differ significantly between the groups (P = .182). CONCLUSION:
      Anatomic resection decreases the risk of tumor recurrence and improves recurrence
      free survival compared with nonanatomic resection in patients with superficial
      hepatocellular carcinoma.

PMID- 29191677
TI  - Inhibition of Toll-like receptor 4 ameliorates experimental postischemic injury
      in the cholestatic liver through inhibition of high-mobility group box protein b1
      (HMGB1) signaling.
AB  - BACKGROUND: The objective of this study was to elucidate whether the inhibition
      of Toll-like receptor 4 attenuates liver injury ischemia/reperfusion in the
      cholestatic liver. METHOD: Rats were assigned into sham, bile duct ligation, sham
      ischemia/reperfusion (ischemia/reperfusion after laparotomy), and bile duct
      ligation ischemia/reperfusion (ischemia/reperfusion after bile duct ligation)
      groups. In some rats, TAK-242, an inhibitor of Toll-like receptor 4, was
      administered 15 minutes before ischemia/reperfusion. We measured intrahepatic
      Toll-like receptor 4 expression, serum hepatic marker expression, liver necrosis,
      gene expression of inflammation-associated factors, and serum high-mobility group
      box protein b1 levels. RESULTS: Intrahepatic Toll-like receptor 4 expression was
      significantly greater in the bile duct ligation group than in the sham group.
      Toll-like receptor 4 expression was further increased after ischemia/reperfusion
      in bile duct ligation ischemia/reperfusion groups. The levels of serum hepatic
      markers were significantly greater in both the sham ischemia/reperfusion and bile
      duct ligation ischemia/reperfusion groups than in the groups without
      ischemia/reperfusion. Liver necrosis was greater in the bile duct ligation group
      than in the sham group and was further increased in the bile duct ligation
      ischemia/reperfusion group. Genomic expression of inflammation-associated factors
      was also significantly greater in the bile duct ligation ischemia/reperfusion
      group than in the sham group. Serum high-mobility groups box protein b1 levels
      were greater in the bile duct ligation ischemia/reperfusion group than in the
      sham group (28.1 ng/ml versus 9.2 ng/ml, P = .011) and the bile duct ligation
      group (28.1 ng/ml versus 10.6 ng/ml, P = .017). These changes in the bile duct
      ligation ischemia/reperfusion group were significantly attenuated by
      preconditioning with TAK242. CONCLUSIONS: Toll-like receptor 4 inhibition has a
      potential to minimize severe injury after ischemia/reperfusion in the cholestatic
      liver through inhibition of high-mobility groups box protein b1.

PMID- 29191678
TI  - Comparison of digital color fundus imaging and fluorescein angiographic findings
      for the early detection of diabetic retinopathy in young type 1 diabetic
      patients.
AB  - PURPOSE: To compare the findings from digital 7-field color fundus (CF)
      photography and fundus fluorescein angiography (FFA) in young patients with
      diabetes mellitus (DM) type 1 without known diabetic retinopathy. METHODS: In
      this prospective, observational cohort study, 54 type 1 diabetic patients were
      recruited. Participants had been diagnosed with diabetes mellitus (DM) for at
      least 6 years, had Best Corrected Visual Acuity of 20/25 or better and did not
      have any known retinal pathology. One hundred and seven eyes were analyzed. All
      patients underwent a complete ophthalmic examination in the Retina Service of a
      University Eye Clinic including digital CF imaging and FFA. RESULTS: The mean age
      of the patients was 18.6 years. Mean duration of DM was 11.3 years, and mean
      haemoglobin A1c (HbA1c) level was 8.6%. Of the 107 eyes, 8 eyes (7.5%) showed
      microvascular abnormalities on CF images, while FFA images revealed changes in 26
      eyes (24.3%). Hence, 18 of the 26 eyes showing abnormalities on FFA did not show
      any abnormalities on CF images. Mean DM duration in the patient group with
      detectable microvascular changes was found to be significantly higher compared to
      patients without changes, while no difference in HbA1c levels, serum lipid levels
      or blood pressure was observed. CONCLUSIONS: Comparison of digital CF and FFA
      findings for the detection of diabetic microvascular changes in type 1 diabetic
      patients showed that FFA reveals more information about retinal vascular
      pathology for early detection of diabetic retinopathy.

PMID- 29191680
TI  - Food allergy: Update on prevention and tolerance.
AB  - Of the many possible hypotheses that explain the recent increase in childhood
      food allergy (FA), the dual-allergen exposure hypothesis has been the most
      extensively investigated. This chapter serves as a review and update on the
      prevention of FA and focuses on recently published randomized controlled trials
      exploring the efficacy of oral tolerance induction in infancy for the prevention
      of FA. As a result of these RCTs, National Institutes of Health recommendations
      now actively encourage the early introduction of peanut for the prevention of
      peanut allergy, and other countries/settings recommend the inclusion of potential
      common food allergens, including peanut and egg, in complementary feeding
      regimens commencing at approximately 6 months but not before 4 months of age.
      Further studies that explore the efficacy of oral tolerance induction to other
      common food allergens and that focus on optimal timing, duration, and adherence
      are required.

PMID- 29191679
TI  - Intraocular pressure measurements and corneal biomechanical properties using a
      dynamic Scheimpflug analyzer, after several keratoplasty techniques, versus
      normal eyes.
AB  - PURPOSE: To evaluate the biomechanical properties of the cornea and their impact
      on intraocular pressure (IOP) measurement after lamellar keratoplasty, compared
      to healthy eyes, using a non-contact tonometer with a Scheimpflug camera.
      METHODS: This study, from 2014 to 2015, included 22 primary DSAEK, 5 DALK, 6
      DSAEK after PK, and 50 control eyes. Using a non-contact tonometer with a high
      speed Scheimpflug camera (CORVIS ST, Oculus Optikgerate GmbH, Wetzlar, Germany),
      several biomechanical parameters were recorded, including radius at highest
      concavity (Rhc) and defomation amplitude (DA). Central corneal thickness (CCT)
      and uncorrected IOP, were also recorded. For the control eyes only, a corrected
      IOP was calculated, based on age, central corneal thickness, and biomechanical
      parameters. RESULTS: Rhc was significantly lower after DALK (Rhc=5.54+/-0.71,
      P=0.007) and DSAEK (Rhc=6.26+/-0.77, P=0.042) compared to control eyes
      (Rhc=6.82+/-0.76). DA was higher after DALK and DSAEK, but not significantly
      (respectively 1.24+/-0.09 P=0.41 and 1.22+/-0.15, P=0.923) compared to normal
      eyes (1.18+/-0.15). Uncorrected IOP was not significantly different between post
      keratoplasty and control eyes. In control eyes, the corrected IOP (15.23+/-1.88)
      was lower than the uncorrected IOP (16.10+/-2.34); a statistically significant
      positive correlation between Rhc and CCT (R2=0.6020, P<0001), and a significant
      negative correlation between DA and CCT (R2=-0.641, P<0.0001) were found.
      CONCLUSION: Our study showed that, after lamellar keratoplasty, corneal
      biomechanics are altered. Corneas with higher ocular rigidity will show a lower
      DA and a higher Rhc.

PMID- 29191681
TI  - Social behavior-induced multistability in minimal competitive ecosystems.
AB  - Mimimal models of coordinated behavior of populations living in the same
      environment are introduced for the cases when they either both gain by mutual
      interactions, or one hunts the other one, or finally when they compete with each
      other. The equilibria of the systems are analysed, showing that in some cases the
      populations may both disappear. Coexistence leads to global asymptotic stability
      for symbiotic populations, or to Hopf bifurcations for predator-prey systems.
      Finally, a new very interesting phenomenon is discovered in the competition case:
      tristability may be achieved showing that the principle of competitive exclusion
      fails in this case. Indeed either one of the competing populations may thrive,
      but also the case of populations coexistence is allowed, for the same set of
      parameter values.

PMID- 29191682
TI  - Complete mitochondrial genome of Saturnia jonasii (Lepidoptera: Saturniidae):
      Genomic comparisons and phylogenetic inference among Bombycoidea.
AB  - The complete mitochondrial genome (mitogenome) of Saturnia jonasii (Lepidoptera:
      Saturniidae) was sequenced and compared to those of 19 other bombycoid species.
      Furthermore, the mitogenome sequences were used to infer phylogenetic
      relationships among bombycoid species. The 15,261-bp Saturnia jonasii mitogenome
      contained the typical sets of genes and gene arrangements found in majority of
      Lepidoptera. All Bombycoidea species, including Saturnia jonasii, have a 15-33-bp
      spacer sequence at the trnS2-ND1 junction. The phylogenetic reconstruction of
      bombycoid species consistently and strongly supported monophylies of the
      families, Saturniidae, Bombycidae, and Sphingidae, based on Bayesian inference
      (BI) and maximum-likelihood (ML) methods. Among these families, the Bombycidae
      and Sphingidae species consistently showed a sister relationship, regardless of
      data partitions; the BI method strongly supported this relationship, whereas it
      was moderately supported using the ML method.

PMID- 29191683
TI  - Clinical outcome after 36 months of treatment with injections of autologous blood
      for recurrent dislocation of the temporomandibular joint.
AB  - We investigated the prognosis after three years of treatment for recurrent
      dislocation of the temporomandibular joint with autologous blood given
      intravenously in 21 patients with a mean (range) age 64 (17-92) years of whom 16
      had coexisting systemic disease. The mean (range) follow up from the first
      injection was 64 (41-99) months. Eighteen patients had no recurrence during the
      first 36 months after their first injection, which showed that this minimally
      invasive treatment was effective, particularly for those who had conditions that
      made a mouthpiece or operation unsuitable.

PMID- 29191685
TI  - Breast MRI as a Problem-solving Study in the Evaluation of BI-RADS Categories 3
      and 4 Microcalcifications: Is it Worth Performing?
AB  - RATIONALE AND OBJECTIVES: We aimed to investigate the utility of problem-solving
      breast magnetic resonance imaging (MRI) for mammographic Breast Imaging Reporting
      and Data System (BI-RADS) categories 3 and 4 microcalcifications. MATERIALS AND
      METHODS: Between January 1, 2010 and December 31, 2011, 138 women with 146 areas
      of categories 3 and 4 microcalcifications without sonographic correlates
      underwent breast MRI and had a stereotactic core biopsy using an 11-gauge needle
      or follow-up at least for 24 months. Positive predictive value (PPV), negative
      predictive value, sensitivity, and specificity were calculated on the basis of BI
      RADS category, with categories 1-3 being considered benign and categories 4 and 5
      being considered malignant. RESULTS: Twenty-four cases (16.4%) were malignant (18
      ductal carcinoma in situ, 6 invasive). MRI increased PPV and specificity from 43%
      to 68% and from 80% to 93% (P = .054 and .005) compared to mammography. Within
      102 category 3 microcalcifications, 5 carcinomas were assessed correctly as
      category 4 by MRI. Within 44 category 4 microcalcifications, a correct diagnosis
      was made by MRI in 77% (34 of 44) as opposed to 43% (19 of 44) by mammography,
      and 80% (20 of 25) of unnecessary biopsies could have been avoided. Within the 24
      carcinomas, 5 were negative at MRI. MRI-negative carcinomas have a significantly
      higher possibility of being low grade (ductal carcinoma in situ or invasive) (P =
      .0362). CONCLUSIONS: Breast MRI has the potential to improve the diagnosis of
      category 3 or 4 microcalcifications and could alter indications for biopsy.
      Breast MRI could help predict the presence or absence of higher-grade carcinoma
      for category 3 or 4 microcalcifications.

PMID- 29191684
TI  - Model-based Iterative Reconstruction in Low-radiation-dose Computed Tomography
      Colonography: Preoperative Assessment in Patients with Colorectal Cancer.
AB  - RATIONALE AND OBJECTIVES: To assess the effect of model-based iterative
      reconstruction (MBIR) on image quality and diagnostic performance of low
      radiation-dose computed tomography colonography (CTC) in the preoperative
      assessment of colorectal cancer. MATERIALS AND METHODS: This study included 30
      patients with colorectal cancer referred for surgical treatment. All patients
      underwent CTC with a standard dose (SD) protocol in the supine position and a low
      dose (LD; radiation dose reduction of approximately 85%) protocol in the prone
      position. The SD protocol images were post-processed using filtered back
      projection (FBP), whereas the LD protocol images were post-processed using FBP
      and MBIR. Objective and subjective image quality parameters were compared among
      the three different methods. Preoperative evaluations, including site, length,
      and tumor and node staging were performed, and the findings were compared to the
      postsurgical findings. RESULTS: The mean image noise of SD-FBP, LD-FBP, and LD
      MBIR images was 17.3 +/- 3.2, 40.5 +/- 10.9, and 11.2 +/- 2.0 Hounsfield units,
      respectively. There were significant differences for all comparison combinations
      among the three methods (P < .01). For image noise, the mean visual scores were
      significantly higher for SD-FBP and LD-MBIR than for LD-FBP, and the scores for
      SD-FBP and LD-MBIR were equivalent (3.9 +/- 0.3 [SD-FBP], 2.0 +/- 0.5 [LD-FBP],
      and 3.7 +/- 0.3 [LD-MBIR]). Preoperative information was more accurate under SD
      FBP and LD-MBIR than under LD-FBP, and the information was comparable between SD
      FBP and LD-MBIR. CONCLUSION: MBIR can yield significantly improved image quality
      on low-radiation-dose CTC and provide preoperative information equivalent to that
      of standard-radiation-dose protocol.

PMID- 29191686
TI  - CT Features of Hepatic Veno-occlusive Disease: A Meta-analysis.
AB  - RATIONALE AND OBJECTIVE: The computed tomography (CT) features of hepatic veno
      occlusive disease (HVOD) could play a role in its diagnosis. We aimed to perform
      a meta-analysis of studies examining the CT features of HVOD. METHODS: Relevant
      studies published up to May 3, 2017 were searched in major electronic databases.
      The extracted data included the proportion of various CT features in patients
      with HVOD. The meta-analysis was conducted using R 3.3.3 with the "meta" package.
      RESULTS: Eleven studies were included. The studies involved 326 patients with a
      mean age range of 50.2-58.9 years, and the proportion of female patients ranged
      from 20% to 57.5%. The meta-analysis showed the pooled proportion of CT features:
      hepatic parenchyma with heterogeneous hypoattenuation (81.05%, 95% confidence
      interval [CI]: 56.97%-93.25%), patchy enhancement in the portal venous phase
      (87.09%, 95% CI: 75.15%-93.77%) with or without a narrow or invisible hepatic
      vein (71.02% 95% CI: 42.09%-89.20%), gallbladder wall edema (65.51%, 95% CI:
      28.98%-89.84%), and patchy heterogeneous enhancement in the arterial phase
      (44.36%, 95% CI: 29.98%-59.76%) with or without slightly enlarged hepatic artery
      (56.61%, 95% CI: 40.62%-71.33%). CONCLUSION: Hepatic parenchyma with
      heterogeneous hypoattenuation and patchy enhancement with or without narrowing or
      an invisible hepatic vein in the portal venous or equilibrium phase may be the
      most important CT feature for diagnosing HVOD.

PMID- 29191687
TI  - Interpreting Change in Quantitative Imaging Biomarkers.
AB  - RATIONALE AND OBJECTIVES: Quantitative imaging biomarkers (QIBs) are becoming
      increasingly adopted into clinical practice to monitor changes in patients'
      conditions. The repeatability coefficient (RC) is the clinical cut-point used to
      discern between changes in a biomarker's measurements due to measurement error
      and changes that exceed measurement error, thus indicating real change in the
      patient. Imaging biomarkers have characteristics that make them difficult for
      estimating the repeatability coefficient, including nonconstant error, non
      Gaussian distributions, and measurement error that must be estimated from small
      studies. METHODS: We conducted a Monte Carlo simulation study to investigate how
      well three statistical methods for estimating the repeatability coefficient
      perform under five settings common for QIBs. RESULTS: When the measurement error
      is constant and replicates are normally distributed, all of the statistical
      methods perform well. When the measurement error is proportional to the true
      value, approaches that use the log transformation or coefficient of variation
      perform similarly. For other common settings, none of the methods for estimating
      the repeatability coefficient perform adequately. CONCLUSION: Many of the common
      approaches to estimating the repeatability coefficient perform well for only
      limited scenarios. The optimal approach depends strongly on the pattern of the
      within-subject variability; thus, a precision profile is critical in evaluating
      the technical performance of QIBs. Asymmetric bounds for detecting regression vs
      progression can be implemented and should be used when clinically appropriate.

PMID- 29191688
TI  - Diaphragm and lung-preserving surgery with hyperthermic chemotherapy for
      malignant pleural mesothelioma: A 10-year experience.
AB  - BACKGROUND: The best surgical treatment for malignant pleural mesothelioma is
      still under a debate, but recent evidence points toward a less-invasive approach
      to reduce morbidity and mortality. We reported our 10-year experience of a
      limited surgical approach associated with hyperthermic intrathoracic chemotherapy
      (HITHOC). MATERIAL AND METHODS: Between 2005 and 2014, patients with epithelioid
      or biphasic malignant pleural mesothelioma were treated with lung-diaphragm
      pericardium-sparing pleurectomy associated with double-drug HITHOC; at least 3
      cycles of adjuvant chemotherapy were then administered. The primary outcome
      examined was the feasibility of the procedure, whereas secondary outcomes were
      overall survival and disease-free interval. RESULTS: Among 49 patients, 41 were
      male. Median age was 68 years (35-76 years). Histology was epithelioid in 43
      cases. Pathologic stage I, II, III, and IV occurred in 12, 14, 20, and 3 cases,
      respectively. No intraoperative complications or postoperative mortality
      occurred, whereas morbidity rate was 46.9%. Median hospital stay was 8 days (5-45
      days). Actuarial median overall survival was 22 months and a 1-, 2-, and 5-year
      survival accounted for 79.6%, 45.7%, and 9.9%, respectively. Disease-free
      survival after surgery was 62%, 37.5%, and 18.5% at 1, 2, and 5 years,
      respectively. Risk factors analysis for overall survival confirmed a significant
      role for early stages, epithelioid histology, and fibrinogen serum levels.
      CONCLUSIONS: Cytoreductive surgery associated with HITHOC and adjuvant
      chemotherapy appears feasible and safe, with no mortality and low morbidity.
      Preserving lung and diaphragmatic function might warrant an acceptable long-term
      outcome.

PMID- 29191689
TI  - Does the surgical waiting list affect pathological and survival outcome in
      resectable pancreatic ductal adenocarcinoma?
AB  - BACKGROUND: High-volume centers have to deal with long surgical waiting-lists
      leading to a potential delay in treatment. This study assessed whether a longer
      time from diagnosis to surgery worsened pathological and survival outcomes in
      resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: A retrospective
      analysis of patients treated for resectable PDAC. Difference in size between
      preoperative CT-scan and specimen, pathological features, the rate of vascular
      and R1 resections as well as recurrence and survival were analyzed depending on
      the waiting time using a 30-day cut-off. RESULTS: Waiting more than 30 days for
      surgery was associated with an increase in tumor size on specimen when compared
      with CT-scan (+3 vs. +1 mm, p = 0.04). T and N status, rate of vascular
      resection, grading, perineural and lymphovascular infiltration, and R1 rates did
      not differ between groups, as well as tumor recurrence (48.8% vs. 48.9%, p = 0.5)
      and survival (31 vs. 29 months, p = 0.7). For PDAC < 20 mm, waiting less than 30
      days improved overall survival (p = 0.02). CONCLUSION: The duration of the
      surgical waiting-list did not affect pathological features and survival. Delayed
      surgery was associated with increased cancer size on the specimen. However,
      surgery should not be delayed for PDACs < 20 mm as this may negatively affect the
      prognosis.

PMID- 29191690
TI  - The extent of vascular resection is associated with perioperative outcome in
      patients undergoing pancreaticoduodenectomy.
AB  - BACKGROUND: Few studies have examined the relation between extent of vascular
      resection and morbidity following pancreaticoduodenectomy (PD) with vein
      resection (PDVR). METHODS: Patients undergoing PD for malignancy were identified
      using the American College of Surgeons National Surgical Quality Improvement
      Project from 2006 to 2013. Current procedural terminology codes were used to
      characterize PDVR. RESULTS: 9235 patients underwent PD, 977 (10.6%) had PDVR -
      640 with direct and 224 with graft repair. PDVR had longer operative times (456
      +/- 136 vs 374 +/- 128 min, p < 0.05) and higher intraoperative transfusions (1.8
      +/- 3.4 vs 4.3 +/- 4.9 units, p < 0.05) than PD alone. On adjusted multivariable
      regression, PDVR with either direct or graft repairs was associated with higher
      rates of overall morbidity (OR [odds ratio] 1.50 for direct, 1.74 for graft, p <
      0.05), bleeding (OR 2.18 for direct, 3.26 for graft, p < 0.05), and DVT (OR 2.12
      for direct, 2.62 for graft, p < 0.05) compared to PD alone. Graft repair was
      further associated with increased risk of reoperation (OR 1.59), septic shock (OR
      2.77) and 30-day mortality (OR 2.72), all p < 0.05. DISCUSSION: The risk of
      significant morbidity and mortality for PDVR is associated with the extent of
      vascular resection, with graft repairs having increased morbidity and mortality
      rates.

PMID- 29191691
TI  - Assessing the impact of conversion on outcomes of minimally invasive distal
      pancreatectomy and pancreatoduodenectomy.
AB  - BACKGROUND: Our aim was to compare outcomes of patients who undergo conversion to
      open during minimally invasive distal pancreatectomy (MI-DP) and
      pancreatoduodenectomy (MI-PD) to those completed in minimally invasive fashion,
      and to compare outcomes of minimally invasive completions and conversions to
      planned open pancreatectomy. METHODS: Propensity scoring was used to compare
      outcomes of completed and converted cases from a national cohort, and
      multivariate regression analysis (MVA) was used to compare minimally invasive
      completions and conversions to planned open pancreatectomy. RESULTS: MI-DP was
      performed in 43.0%. Conversions (20.2%) had increased morbidity (32.3 vs 42.0%),
      serious morbidity (11.1 vs 21.2%), and organ space infection (6.2 vs 14.2%).
      Outcomes of MI-DP conversions were comparable to open. MI-PD was performed in
      6.1%. Conversions (25.2%) had increased organ space infection (10.9 vs 26.6%),
      blood transfusions (17.2 vs 42.2%), and clinically relevant pancreatic fistula
      (11.5 vs 28.1%). On MVA, conversion of MI-PD was associated with increased
      mortality (OR 2.84, 95% CI 1.09-7.42), post-operative percutaneous drain
      placement (OR 2.36, 95% CI 1.32-4.20), and blood transfusions (OR 1.85, 95% CI
      1.07-3.21). CONCLUSION: Converted cases have increased morbidity compared to
      completions, and for patients undergoing PD, conversions may be associated with
      inferior outcomes compared to planned open cases.

PMID- 29191692
TI  - Thermodynamic properties of an emerging chemical disinfectant, peracetic acid.
AB  - Peracetic acid (PAA or CH3COOOH) is an emerging disinfectant with a low potential
      to form carcinogenic disinfection by-products (DBPs). Basic thermodynamic
      properties of PAA are, however, absent or inconsistently reported in the
      literature. This review aimed to summarize important thermodynamic properties of
      PAA, including standard Gibbs energy of formation and oxidation-reduction (redox)
      potential. The standard Gibbs energies of formation of CH3COOOH(aq), CH3COOOH(g),
      CH3COOOH(l), and CH3COOO(aq)- are -299.41kJ.mol-1, -283.02kJ.mol-1, -276.10kJ.mol
      1, and -252.60kJ.mol-1, respectively. The standard redox potentials of PAA are
      1.748V and 1.005V vs. standard hydrogen electrode (SHE) at pH 0 and pH 14,
      respectively. Under biochemical standard state conditions (pH 7, 25 degrees C,
      101,325Pa), PAA has a redox potential of 1.385V vs. SHE, higher than many
      disinfectants. Finally, the environmental implications of the thermodynamic
      properties of PAA were systematically discussed. Those properties can be used to
      predict the physicochemical and biological behavior of aquatic systems exposed to
      PAA.

PMID- 29191693
TI  - Association between rs823128 polymorphism and the risk of Parkinson's disease: A
      meta-analysis.
AB  - Numerous published case-control studies have investigated a role of PARK16 gene
      in susceptibility to Parkinson's disease (PD), but the results remain conflicting
      and under-powered. Herein, we performed this meta-analysis to evaluate the
      possible association between the polymorphism of the PARK16 rs8231128 (A/G) and
      PD.A comprehensive search of six databases was conducted to identify all case
      control studies involving PARK16rs823128variants and PD risk up to August 2017.
      The strict inclusion and exclusion criteria were applied. A total of 9 studies
      including 15 case-control studies with 7277 PD cases and 6188 controls were
      included in the meta-analysis. And STATA 12.0 statistics software was used to
      calculate available data from each study. The crude odds ratios (OR) and 95%
      confidence interval (CI) were calculated to assess the genetic association
      between PARK16 rs823128 polymorphism and the risk of PD. In the combined
      analysis, results showed a significant association between rs823128 and PD in
      allelic model(G vs. A: OR=0.886, 95% CI=0.811-0.969, P=0.008), dominant model
      (GG+ AG vs. AA: OR=0.886, 95% CI=0.804-0.976, P=0.014), and heterozygote model
      (AG vs. AA: OR=0.897, 95% CI=0.812-0.991, P=0.032). Further, ethnicity based
      analysis showed a significant association in Asian and Chilean population, but
      not in Caucasian samples. Within its limitations, this meta-analysis demonstrated
      that the rs823128 variants(G allele, GA and GG genotype)in PARK16 might be a
      potential protective factor for PD. However, these associations vary in different
      ethnicities.

PMID- 29191694
TI  - Frontal evoked gamma activity modulates behavioural performance in Autism
      Spectrum Disorders in a perceptual simultaneity task.
AB  - Autism spectrum disorders (ASDs) are associated with anomalies in time
      perception. In a perceptual simultaneity task, individuals with ASD demonstrate
      superior performance compared to typically developing (TD) controls. gamma
      activity, a robust marker of visual processing, is reportedly altered in ASD in
      response to a wide variety of tasks and these differences may be related to
      superior performance in perceptual simultaneity. Using time-frequency analysis,
      we assessed evoked gamma-band phase-locking in magnetoencephalographic recordings
      of 16 ASD individuals and 17 age-matched TD controls. Individuals judged whether
      presented visual stimuli were simultaneous or asynchronous. We identified left
      frontal gamma-activity in ASD, which was associated with a reduced perception of
      simultaneity. Where feature binding was observed at a neurophysiological level in
      parieto-occipital cortices in ASD in apparent simultaneity (asynchronous stimuli
      with short delay between them), this did not predict the correct behavioural
      outcome. These findings suggest distinct gamma profiles in ASD associated with
      the perception of simultaneity.

PMID- 29191695
TI  - Association of circulating manganese levels with Parkinson's disease: A meta
      analysis.
AB  - Whether systemic manganese (Mn) dysfunctions in Parkinson's Disease (PD) is still
      under ongoing debate. The recent reported studies on the circulating Mn levels in
      PD showed inconsistent results. A meta-analysis study was conducted to evaluate
      the association of circulating Mn levels with PD, and to clarify whether Mn
      should be considered as a potential risk factor for PD. A systematic searching
      was performed based on PubMed, web of science, and China National Knowledge
      Infrastructure (CNKI). Finally, 22 studies were identified, involving 637 PD
      patients and 802 health controls (HC) individuals for serum Mn, 1258 PD patients
      and 1304 HC individuals for peripheral blood Mn, and 195 PD patients and 196 HC
      individuals for cerebrospinal fluid (CSF) Mn. Forest plots were adopted to
      represent the comparison of the groups by assessing standardized mean difference
      with random effects model. This meta-analysis revealed a significantly increased
      serum Mn levels in PD patients (SMD=0.78; 95% CI [0.32, 1.24]; P=0.001), and it
      was further confirmed when serum, plasma and whole blood studies were analyzed
      together (SMD=0.58; 95% CI [0.25, 0.91]; P=0.001). Instead, no significant
      differences of CSF Mn were observed between PD patients and HC individuals (SMD=
      0.09; 95% CI [-0.47, 0.29]; P=0.644). These results supported the notion that
      elevated Mn level should be a potential risk factor for PD, although the high
      heterogeneity and methodological limitations recommended caution in the
      interpretations for the present findings.

PMID- 29191696
TI  - Modulating effect of low intensity pulsed ultrasound on the phenotype of
      inflammatory cells.
AB  - AIMS: The purpose of this study was toclarify the effect of low intensity pulsed
      ultrasound (LIPUS) on the phenotype of the inflammatory infiltrate in muscle
      tissue following acute injury. MAIN METHODS: Forty Wistar rats were submitted to
      cryoinjury of the tibialis anterior muscle and only half were treated with LIPUS.
      After 1, 2, 3 and 7 days macrophages and neutrophils were quantified. KEY
      FINDINGS: With one day, LIPUS led to reductions in the number of neutrophils and
      M1 macrophages. After two days, muscles treated with LIPUS had fewer total
      macrophages and M1 macrophages, but a greater number of M2 macrophages. Muscles
      treated with LIPUS showed fewer macrophages after three and seven days.
      SIGNIFICANCE: As the permanence of cells with pro-inflammatory and anti
      inflammatory action can lead to the perpetuation of inflammation with consequent
      tissue damage and tissue fibrosis, respectively, the ability of LIPUS to modulate
      the occurrence of these cells demonstrates the therapeutic potential of this
      resource.

PMID- 29191697
TI  - Deliverable transgenics & gene therapy possibilities for the testes.
AB  - Male infertility and hypogonadism are clinically prevalent conditions with a high
      socioeconomic burden and are both linked to an increased risk in cardiovascular
      metabolic diseases and earlier mortality. Therefore, there is an urgent need to
      better understand the causes and develop new treatments for these conditions that
      affect millions of men. The accelerating advancement in gene editing and delivery
      technologies promises improvements in both diagnosis as well as affording the
      opportunity to develop bespoke treatment options which would both prove
      beneficial for the millions of individuals afflicted with these reproductive
      disorders. In this review, we summarise the systems developed and utilised for
      the delivery of gene therapy and discuss how each of these systems could be
      applied for the development of a gene therapy system in the testis and how they
      could be of use for the future diagnosis and repair of common male reproductive
      disorders.

PMID- 29191698
TI  - MicroRNAs-361-5p and miR-574-5p associate with human adipose morphology and
      regulate EBF1 expression in white adipose tissue.
AB  - Reduced adipose expression of the transcription factor Early B cell factor 1
      (EBF1) is linked to white adipose tissue (WAT) hypertrophy. We aimed to identify
      microRNAs (miRNAs) associated with WAT hypertrophy and EBF1 regulation. We mapped
      WAT miRNA expression from 26 non-obese women discordant in WAT morphology and
      determined EBF1 activity in the non-obese and 30 obese women. Expression of 15
      miRNAs was higher in hypertrophy and 10 were predicted to target EBF1. Binding of
      miR-365-5p/miR-574-5p were validated with 3'-UTR assay. Overexpression of miR-365
      5p or miR-574-5p reduced EBF1 while inhibition of miR-574 increased EBF1
      expression in human adipocytes in vitro. Additive effects on EBF1 were observed
      when concomitantly overexpressing both miRNAs. EBF1 targets were affected by over
      expression/inhibition of either miRNAs. Finally, miR-365-5p/miR-574-5p expression
      in 56 individuals correlated significantly with EBF1 activity. Our results
      suggest that miR-365-5p and miR-574-5p may be linked to WAT hypertrophy via
      effects on EBF1 expression.

PMID- 29191699
TI  - In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against
      cutaneous, mucocutaneous and visceral Leishmania species.
AB  - The identification of specific therapeutic targets and the development of new
      drugs against leishmaniasis are urgently needed, since chemotherapy currently
      available for its treatment has several problems including many adverse side
      effects. In an effort to develop new antileishmanial drugs, in the present study
      a series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives was synthesized and
      evaluated in vitro against Leishmania mexicana promastigotes. Compounds 7 and 8
      with the highest antileishmanial activity (micromolar) and lower cytotoxicity
      than miltefosine and amphotericin B were selected to evaluate their activity
      against L. braziliensis 9and L. donovani, species causative of mucocutaneous and
      visceral leishmaniasis, respectively. Compound 7 showed significantly higher
      activity against L. braziliensis promastigotes than compound 8 and slightly lower
      than miltefosine. Compounds 7 and 8 had IC50 values in the micromolar range
      against the amastigote of L. mexicana and L. braziliensis. However, both
      compounds did not show better activity against L. donovani than miltefosine.
      Compound 8 showed the highest SI against both parasite stages of L. mexicana. In
      addition, compound 8 inhibited 68.27% the activity of recombinant L. mexicana
      arginase (LmARG), a therapeutic target for the treatment of leishmaniasis.
      Docking studies were also performed in order to establish the possible mechanism
      of action by which this compound exerts its inhibitory effect. Compound 8 shows
      promising potential for the development of more potent antileishmanial
      benzimidazole derivatives.

PMID- 29191700
TI  - Health Care Utilization in the First Month After Birth and Its Relationship to
      Newborn Weight Loss and Method of Feeding.
AB  - OBJECTIVE: Guidelines recommend closer outpatient follow-up for exclusively
      breastfed newborns, especially those with pronounced weight loss, because of
      increased risk of hyperbilirubinemia and dehydration that might require
      readmission. Our objective was to determine how feeding method and weight loss
      are associated with neonatal health care utilization. METHODS: A retrospective
      cohort study conducted at Northern California Kaiser Permanente hospitals in 2009
      2013 assessed 143,889 neonates to study the inpatient method of feeding as well
      as inpatient and outpatient weights. The main outcome measures were inpatient and
      outpatient health care utilization in the 30 days after birth. RESULTS: Newborn
      weight loss and feeding method were both associated with utilization. Exclusively
      breastfed newborns had higher readmission rates than those exclusively formula
      fed for both vaginal (4.3% compared to 2.1%) (P < .001) and cesarean deliveries
      (2.1% compared to 1.5%) (P = .025). Those exclusively breastfed also had more
      neonatal outpatient visits compared to those exclusively formula fed for both
      vaginal (means of 3.0 and 2.3, P < .001) and cesarean deliveries (means of 2.8
      and 2.2, P < .001). Among vaginally delivered newborns of all feeding types,
      newborns with weight loss >10% at discharge had a relative risk of readmission of
      1.10 (95% confidence interval [CI],1.00, 1.20) compared to those with <8% weight
      loss at discharge; among the subset weighed as inpatients or outpatients between
      48 and 72 hours, those with >10% weight loss between 48-72 hours had a relative
      risk of readmission of 2.11 (95% CI, 1.95, 2.26) compared to those with <8%
      weight loss at 48-72 hours. CONCLUSIONS: Exclusive breastfeeding and weight loss
      are associated with increased neonatal health care utilization. Improving
      clinical management of exclusively breastfed neonates with pronounced weight loss
      might reduce health care utilization.

PMID- 29191701
TI  - Back Pain and Body Posture Evaluation Instrument for Adults: Expansion and
      Reproducibility.
AB  - BACKGROUND: The BackPEI questionnaire was developed and validated just
      exclusively to evaluate children. AIMS: To propose, validate, and test the
      reproducibility of an expanded version of the Back Pain and Body Posture
      Evaluation Instrument (BackPEI), originally designed to assess back pain in
      school-aged children, for use with adults. DESIGN: Validation Study. METHODS:
      Five questions from the original BackPEI were replaced, resulting in the revised
      instrument (BackPEI-A) containing 20 questions. Three experts checked the content
      validity of the revised instrument, and the reproducibility was tested by
      trialing the questionnaire with 154 adults. RESULTS: The reproducibility data for
      the questions regarding pain intensity, analyzed using the Wilcoxon test and
      intraclass correlation coefficient (ICC), indicated that (a) there was no
      difference between the medians and (b) the answers were highly correlated, both
      for lower back (p = .574) (ICC = 0.908) and cervical (p = .968) (ICC = 0.865)
      pain. The reproducibility data for the remaining questions analyzed using the
      kappa coefficient were classified as moderate (0.4 < kappa <= 0.6) or very good
      (kappa > 0.8). CONCLUSION: The BackPEI-A is a reproducible, valid, and reliable
      instrument for use in the evaluation of back and neck pain and their associated
      risk factors. The instrument also facilitates the evaluation of postural habits
      in activities of daily living in adults.

PMID- 29191702
TI  - Association of initial recorded rhythm and underlying cardiac disease in sudden
      cardiac arrest.
AB  - BACKGROUND: Asystole (ASY) and pulseless electrical activity (PEA) are increasing
      and ventricular fibrillation (VF) or ventricular tachycardia (VT) declining as
      presenting rhythms of sudden cardiac arrest (SCA). Since there is limited
      information on possible differences in the etiology of underlying structural
      heart disease, we analyzed the clinical and/or autopsy findings of victims with
      ASY, PEA or VT/VF. METHODS: All SCA cases with recorded ASY, PEA or VT/VF
      occurring after onset of witnessed collapse were analyzed by the emergency
      personnel between the years 2007-2012 within the Oulu University Hospital area.
      Underlying structural heart disease was diagnosed by medico-legal autopsy or by
      clinical investigation (echocardiography, angiography). Of a total number of 659
      subjects with a documented rhythm at the time of SCA, 300 were determined to be
      due to cardiac disease at autopsy or as a result of clinical investigation. Delay
      was less than 30min from collapse to rhythm recording in 274 subjects (mean age
      65+/-14 yrs; 214 males, 78.1%). RESULTS: The presenting rhythm was ASY in 87
      (31.8%) PEA in 38 (13.9%) and VT/VF in 149 subjects (54.4%). There was no
      significant difference in the delay from the onset of collapse to the rhythm
      recording between ASY (11+/-8min) and VT/VF (9+/-6min, p=0.06) or PEA (6+/-8min)
      and VT/VF (p=0.334). The majority of SCA subjects had an ischemic cause for the
      event (n=216, 78.8%). Non-ischemic cause for SCA was associated with non
      shockable rhythm (Non-ischemic: ASY 46.6% PEA 17.2% VT/VF 36.2% v. Ischemic: ASY
      27.8% PEA 13.0% VT/VF 59.3%) even when adjusted for gender, age and delay from
      collapse to rhythm recording (ASY/PEA v. VT/VF, OR 3.2 95%CI: 1.67-6.50,
      p=0.001). CONCLUSIONS: Asystole and PEA are a more common presenting rhythm than
      VT/VF at the time of SCA in non-ischemic cardiac disease. The decreasing trend of
      ischemic heart disease as a cause of SCA may partly explain the increasing trend
      of ASY/PEA.

PMID- 29191703
TI  - Assessing health-related quality of life (HRQoL) in survivors of out-of-hospital
      cardiac arrest: A systematic review of patient-reported outcome measures.
AB  - AIM: High quality evidence of out-of-hospital cardiac arrest (OHCA) survivors'
      health-related quality of life (HRQoL) can measure the long-term impact of CA.
      The aim of this study was to critically appraise the evidence of psychometric
      quality and acceptability of measures used in the assessment of HRQoL in cardiac
      arrest survivors. METHODS: Systematic literature searches (2004-2017) and named
      author searches to identify articles pertaining to the measurement of HRQoL. Data
      on study quality, measurement and practical properties were extracted and
      assessed against international standards. RESULTS: From 356 reviewed abstracts,
      69 articles were assessed in full. 25 provided evidence for 10 measures of HRQoL:
      one condition-specific; three generic profile measures; two generic index; and
      four utility measures. Although limited, evidence for measurement validity was
      strongest for the HUI3 and SF-36. However, evidence for reliability, content
      validity, responsiveness and interpretability and acceptability was generally
      limited or not available in the CA population for all measures. CONCLUSIONS: This
      review has demonstrated that a measure of quality of life specific to OHCA
      survivors is not available. Limited evidence of validity exists for one utility
      measure - the HUI3 - and a generic profile - the SF-36. Robust evidence of the
      quality and acceptability of HRQoL measures in OHCA was limited or not available.
      Future collaborative research must seek to urgently establish the relevance and
      acceptability of these measures to OHCA survivors, to establish robust evidence
      of essential measurement and practical properties over the short and long-term,
      and to inform future HRQoL assessment in the OHCA population.

PMID- 29191704
TI  - Microfouling inhibition of human nosocomial pathogen Pseudomonas aeruginosa using
      marine cyanobacteria.
AB  - Pseudomonas aeruginosa is a Gram negative, opportunistic biofilm forming
      pathogenic bacterium which is developing as a serious problem worldwide. The
      pathogenicity of P. aeruginosa mainly depends upon biofilm and quorum sensing
      (QS) mechanism. Targeting biofilm and QS regulated factor will automatically
      reduce the pathogenicity of P. aeruginosa. Therefore it is compulsory to identify
      naturally derived biofilm and QS inhibitors against P. aeruginosa. In the present
      study Oscillatoria subuliformis, a marine cyanobacterium was used against the
      biofilm and QS of P. aeruginosa. O. subuliformis intracellular methanolic extract
      (OME) at different concentration (1.5 MUg mL-1, 3 MUg mL-1 and 5 MUg mL-1) was
      tested against several virulence factors like Extracellular Polymeric Substance
      (EPS), Cell Surface Hydrophobicity (CSH), elastase, pyocyanin and swarming
      motility. OME inhibited biofilm (56%), EPS (40%), CSH (56%), pyocyanin (27%),
      elastase activity and swarming motility in P. aeruginosa without interfering in
      their survival. Characterization of the OME using FTIR and GCMS confirmed
      palmitic acid and oleic acid as active compound. CLSM analysis of catheter coated
      with OME, palmitic and oleic acid proved biofilm inhibition over urinary
      catheters. The results postulates that oleic and palmitic acid could be an
      effective attenuator of P. aeruginosa pathogenesis.

PMID- 29191705
TI  - Integrated analysis of miRNA and mRNA expression profiling in bovine endometrial
      cells in response to lipopolysaccharide-stimulation.
AB  - MicroRNAs (miRNA) play an important role in regulating gene expression, making
      them important resources for exploring molecular mechanisms. Molecular mechanisms
      involved in the inflammatory responses of bovine endometrial cells induced by
      lipopolysaccharide (LPS) have not been widely studied. In the present study,
      miRNA and mRNA expression profiling of bovine endometrial cells treated with 1
      MUg/mL LPS for 24 h were evaluated by RNA-Seq (RNA-sequencing). The results
      showed that LPS induced 20 (11 up- and 9 down-regulated) differentially-expressed
      miRNAs and 108 (90 up- and 18 down-regulated) differentially-expressed mRNAs of
      bovine endometrial cells. The results for 5 mRNAs and 4 miRNAs were evaluated by
      quantitative real-time PCR (qRT-PCR) to validate the reliability of the RNA-seq
      data. Integrating analysis of the miRNA and mRNA expression profiles revealed 116
      miRNA-target gene pairs. GO and KEGG pathway analysis of differentially expressed
      miRNAs and target genes predicted the likely roles of differentially expressed
      miRNAs in inflammatory responses in bovine endometrial cells induced by LPS. The
      reliability of the integrating analysis of the miRNA and mRNA data were validated
      by measuring the expression of three miRNA-target gene pairs by qRT-PCR. Our
      results improve the understanding of the role of miRNA involvement in
      inflammatory response of bovine endometrial cells induced by LPS.

PMID- 29191706
TI  - Biological control of the Pulse beetle, Callosobruchus maculatus in stored grains
      using the entomopathogenic bacteria, Bacillus thuringiensis.
AB  - In the present study, we reported the biological control of stored product insect
      pest, Callosobruchus maculatus using the entomopathogenic bacteria, Bacillus
      thuringiensis. A significant delay in the larval, pupal and total development
      period of C. maculatus was observed after treatment with B. thuringiensis at 4 *
      108 cells/mL. Furthermore, B. thuringiensis are highly effective in the control
      of C. maculatus and produced 100% mortality at 4 * 108 cells/mL. The LC50 value
      was estimated to be 3 * 107 cells/mL. In addition, a significant decrease in the
      activity of mid-gut alpha-amylase, cysteine protease, alpha & beta-glucosidases,
      lipase, glutathione S-transferase (GST) and lactate dehydrogenase (LDH) was
      observed after treatment with B. thuringiensis at 4 * 108 cells/mL. This study
      concludes that B. thuringiensis are more effective against C. maculatus and could
      be used as a potential biological control agent in the management of stored
      product insect pests in the future.

PMID- 29191707
TI  - Changes in inflammatory/cardiac markers of HIV positive patients.
AB  - : HIV replication promotes atherogenesis and participates in the immune response
      to the virus, thereby influencing the inflammatory profile. These changes may, in
      turn, contribute to the risk of cardiovascular diseases with involvement of
      platelets. However, adenine nucleotides and nucleosides involved in
      thromboregulation and modulation of immune response may therefore be affected by
      these alterations. OBJECTIVES: This study sought to evaluate the profile of pro
      and anti-inflammatory cytokines (IL-10, IL-6, IL-17, TNF, IL-4, IL-2 and IFN
      gamma), cardiac markers (troponin, CK, CK MB, LDH, CRP) in HIV-positive patients
      and assess the in vitro effect of antiretroviral therapy on the activities of
      ectonucleotidases (E-NTPDase and E-5'-nucleotidase) in human platelets. DESIGN
      AND METHODS: Blood samples were obtained from ten HIV positive patients at the
      Infectious Disease Clinic of the University Hospital of Santa Maria, Brazil and
      ten HIV negative individuals (control group) for this study. RESULTS: The results
      revealed that there were significant (P < 0.05) increases in serum levels of IL-6
      and IFN-gamma with no significant (P > 0.05) changes in the serum levels of the
      cardiac markers investigated (CK, CK-MB, troponin, LDH and CRP). In addition, the
      ectonucleotidases (E-NTPDase and E-5'-nucleotidase) activities were not altered
      (P > 0.05) in human platelets when incubated with different antiretroviral drugs
      in vitro. CONCLUSIONS: The results of this study suggest that, despite successful
      treatment, a proinflammatory state is not altered in HIV patients, and that
      antiretroviral therapy per se does not change the purinergic profile.

PMID- 29191708
TI  - Neuroprotective effect of (-)-tetrahydropalmatine in Japanese encephalitis virus
      strain GP-78 infected mouse model.
AB  - Japanese encephalitis virus (JEV), known to affect children, is a major cause of
      severe encephalopathy. Its prevalence has been percolated over wider regions of
      Southern Asia. JEV is associated with neurodegeneration, severe inflammation,
      increased oxidative stress and elevated levels of stress linked proteins. Four
      groups of 15 mice each (4-5 weeks old BALB/c mice of either sex) was used for the
      study. Mice were intravenously infected with lethal dose of 3 * 105 pfu of JEV,
      followed by mortality after 8 days. On the next day and onwards, the animals were
      administered intraperitonially with (-)-tetrahydropalmatine (LTHP) solution (0.1
      mg/mL in PBS) for the next 7 days. Animals exhibited protection against JEV
      infection, after being administered with LTHP. Reduction in levels of, viral
      population, caspase-2 expression, reactive oxygen and nitrogen species,
      microglial cells and proinflammatory mediators, stress linked protein molecules
      and neuronal apoptosis was exhibited in JEV infected animals treated with LTHP.
      The effects produced by the administration of LTHP indicated its possible use to
      treat JEV in mouse model. Potential to reduce viral count in brain and subsequent
      neuronal apoptosis, reduction in mediators of inflammation and oxidative stress,
      strictly advocate the use of LTHP for treatment of JEV. Thus, the present
      investigation indorses LTHP as a potentially strong drug candidate for the
      treatment of JEV infection due to its neuroprotective, anti-inflammatory,
      antiviral and anti-oxidative effect.

PMID- 29191709
TI  - Strigolactones promote rhizobia interaction and increase nodulation in soybean
      (Glycine max).
AB  - Strigolactones (SLs) play an important role in controlling root growth, shoot
      branching, and plant-symbionts interaction. Despite the importance, the
      components of SL biosynthesis and signaling have not been unequivocally explored
      in soybean. Here we identified the putative components of SL synthesis enzymes
      GmMAX1a and GmMAX4a with tissue expression patterns and were apparently regulated
      by rhizobia infection and changed during nodule development. GmMAX1a and GmMAX4a
      were further characterized in soybean nodulation with knockdown transgenic hairy
      roots. GmMAX1a and GmMAX4a knockdown lines exhibit decreased nodule number and
      expression levels of several nodulation genes required for nodule development.
      Hormone analysis showed that GmMAX1a and GmMAX4a knockdown hairy roots had
      increased physiological level of ABA and JA but significantly decreased auxin
      content. This study not only revealed the conservation of SL biosynthesis but
      also showed close interactions between SL and other hormone signaling in
      controlling plant development and legume-rhizobia interaction.

PMID- 29191710
TI  - 2017 ACC/HRS lifelong learning statement for clinical cardiac electrophysiology
      specialists: A report of the ACC Competency Management Committee.

PMID- 29191711
TI  - Analyzing test batteries in animal models of psychopathology with multivariate
      analysis of variance (MANOVA): One possible approach to increase external
      validity.
AB  - BACKGROUND: One concern regarding animal models of psychopathology is unclear
      external validity. One way to establish external validity is to examine measures
      representing separate facets of the pathology with a battery of tests in the same
      cohort of animals. Additionally, utilizing the same animals in a battery of tests
      can help to reduce the number of animals in research. However, issues had been
      raised regarding the analysis of data coming from batteries and the standard
      practice is to analyze each test separately. This approach introduces two
      problems: (1) the analysis answers the question regarding separate tests but not
      regarding the general effect; (2) there is no correction for multiple
      comparisons. One way to overcome these challenges is to use transformations to Z
      scores. We suggest an additional approach, analyzing test batteries with
      multivariate analysis of variance (MANOVA). METHODS: To compare the outcomes of Z
      score analysis and MANOVA we re-analyzed two published studies where data were
      initially analyzed separately for each test. Additionally, we computed effect
      sizes. RESULTS: The first study tested interaction between sex and lithium in a
      battery of manic-like behaviors, the second study tested asenapine in a battery
      of anxiety-like behaviors. For the first study, the MANOVA analysis indicated no
      effects of sex and a significant antimanic-like effect of lithium and for the
      second study, the MANOVA indicated a significant anxiolytic effect of asenapine.
      Z-score analysis resulted in a significant general antimanic-like effect in the
      lithium study but failed to demonstrate the anxiolytic effects of asenapine in
      the second study. CONCLUSIONS: It is possible to suggest that MANOVA is an
      appropriate way to analyze data from test batteries and that its use, when
      appropriate, can increase the validity, predictability and reproducibility of
      results.

PMID- 29191712
TI  - Biochemical and physiological effects of nickel in the euryhaline crab Neohelice
      granulata (Dana, 1851) acclimated to different salinities.
AB  - The estuarine crab Neohelice granulata was maintained under control condition or
      exposed to sublethal concentrations of dissolved Ni (measured: 128 and 1010MUg/L)
      for 96h at different salinities (2 and 30ppt). After metal exposure, whole-body
      oxygen consumption was measured and tissue (hemolymph, gills, hepatopancreas and
      muscle) samples were collected. Control crabs acclimated to 2ppt salinity showed
      lower hemolymph concentrations of Na+ (33%), Mg2+ (19%) and K+ (30%), as well as
      increased LPO levels in anterior gills (379%), posterior gills (457%) and
      hepatopancreas (35%) with respect to those acclimated to 30ppt salinity. In crabs
      acclimated to 2ppt salinity, Ni exposure increased whole-body oxygen consumption
      (75%), hemolymph K+ concentration (52%), hemolymph (135%) and hepatopancreas
      (62%) LDH activity. Also, it reduced hemolymph Cl- concentration (16%) and muscle
      LDH activity (33%). In crabs acclimated to 30ppt salinity, Ni exposure increased
      LDH activity in hemolymph (195%), hepatopancreas (126%) and muscle (53%), as well
      as hemolymph osmolality (10%), Cl- (26%) and Ca2+ (20%) concentration. It also
      reduced hepatopancreas lipid peroxidation (20%) and hemolymph Mg2+ (29%) and K+
      (31%) concentration. These findings indicate that N. granulata is hyper
      osmoregulating in 2ppt salinity and hypo-regulating in 30ppt salinity, showing
      adjustments of hemolymph ionic composition and metabolic rates, with consequent
      higher oxidative damage to lipids in low salinity (2ppt). Ni effects are
      associated with metabolic (aerobic and anaerobic) disturbances in crabs
      acclimated to 2ppt salinity, while osmotic and ionoregulatory disturbances were
      more evident in crabs acclimated to 30ppt salinity.

PMID- 29191713
TI  - Assessment of right atrial function with speckle tracking echocardiography after
      percutaneous closure of an atrial septal defect.
AB  - INTRODUCTION: Speckle tracking echocardiography (STE) for two-dimensional (2D)
      strain analysis is a new tool to assess myocardial function. The aim of this
      study was to assess right atrial (RA) function using STE in patients with an
      atrial septal defect (ASD) before and one month after percutaneous closure.
      METHODS: We prospectively examined 32 consecutive patients (nine male, 23 female)
      who underwent percutaneous transcatheter closure of a secundum ASD between June
      2013 and December 2015. Echocardiography was performed on admission, prior to
      cardiac catheterization and then one month after ASD closure. Peak global RA
      longitudinal strain was analyzed by 2D-STE. RESULTS: Patients' mean age was
      34.6+/-8.2 years. The mean diameter of the occlusive devices was 18.5+/-7.5 mm.
      Right ventricular (RV) end-diastolic diameters were significantly increased but
      decreased significantly after ASD closure (43+/-5 vs. 38+/-4 mm, p<0.05). Left
      atrial (LA) diameters (40+/-8 vs. 37+/-6 mm, p<0.05) decreased significantly
      after the intervention, whereas left ventricular (LV) end-diastolic diameters
      (45+/-5 vs. 46+/-4 mm, NS) remained unchanged. Tricuspid annular plane systolic
      excursion increased significantly (17.6+/-5.4 vs. 22.3+/-8.1 mm, p<0.05). After
      closure of the defect, a significant increase was observed in longitudinal RA
      strain (26.5+/-9.6% vs. 35.3+/-10.5%, p<0.001). CONCLUSIONS: After percutaneous
      transcatheter closure of a secundum ASD, there was an increase in RA longitudinal
      strain. 2D-STE strain analysis appears to be helpful for the assessment of RA
      function and of response to correction of volume overload after percutaneous
      transcatheter closure of a secundum ASD.

PMID- 29191714
TI  - Subcutaneous immunoglobulins in patients with multiple myeloma and secondary
      hypogammaglobulinemia: a randomized trial.
AB  - Multiple myeloma is commonly associated with a reduction of non-paraprotein
      immunoglobulins, resulting in a higher risk of infections that represent the
      leading cause of the patients' death. Therefore, immunoglobulin replacement
      therapy appears a logical approach. A total number of 46 myeloma patients were
      randomly enrolled: 24 of them were assigned to receive subcutaneous
      immunoglobulins, and 22 were controls. The primary endpoint was the evaluation of
      the annual rate of severe infections in immunoglobulins-receiving patients as
      compared with those untreated. Subcutaneous immunoglobulins-treated patients
      showed a significantly lower number of severe infections per year. Adverse events
      were limited to the site of infusion and were easily manageable. Health-related
      quality of life was significantly better in subcutaneous immunoglobulins
      receiving patients. By decreasing the rate of infections, the prophylactic
      administration of SCIg improves both adherence to chemotherapy and health-related
      quality of life, and is cost-effective by reducing the need of hospitalization
      and the use of antibiotics.

PMID- 29191715
TI  - VcR-CVAD Induction Chemotherapy Followed by Maintenance Rituximab Produces
      Durable Remissions in Mantle Cell Lymphoma: A Wisconsin Oncology Network Study.
AB  - INTRODUCTION: VcR-CVAD was developed as an intermediate-intensity induction
      regimen with maintenance rituximab (MR) to improve remission durations after
      first-line therapy for mantle cell lymphoma (MCL) in older and younger patients
      with MCL. PATIENTS AND METHODS: Patients with previously untreated MCL received
      VcR-CVAD induction chemotherapy for 6 cycles (21-day cycles). Patients achieving
      at least a partial response received rituximab consolidation (375 mg/m2 * 4
      weekly doses) and MR (375 mg/m2 every 12 weeks * 20 doses). The primary endpoints
      were overall and complete response (CR), and the secondary endpoints were
      progression-free survival (PFS) and overall survival (OS). Thirty patients were
      enrolled, with a median age of 61 years. There was an even distribution of
      patients < 60 years and >= 60 years. Mantle cell lymphoma international
      prognostic index medium- or high-risk disease was present in 60%. The overall
      response rate observed was 90% (77% CR/unconfirmed CR). After a median follow-up
      of 7.8 years, the 6-year PFS and OS were 53% and 70%, respectively. There was no
      difference in 6-year PFS or OS between the younger (age < 60 years) and older
      (age >= 60 years) subgroups. In a univariate analysis, lactate dehydrogenase,
      when analyzed for interaction with age, had a significant effect on PFS outcomes
      at 6 years. There were no pretreatment variables determined to have a significant
      effect on OS outcomes at 6 years. CONCLUSIONS: Long-term outcomes with VcR-CVAD
      are comparable with more intensive inductions and consolidation approaches. MCL
      is biologically heterogeneous, and durable remission can be achieved with
      intermediate intensity therapy. MR appears to contribute to these excellent
      outcomes.

PMID- 29191716
TI  - Pulmonary absorption - estimation of effective pulmonary permeability and tissue
      retention of ten drugs using an ex vivo rat model and computational analysis.
AB  - Permeation of inhaled drugs across the pulmonary epithelium can regulate the rate
      and extent of local drug absorption and hence the pulmonary tissue concentration.
      Therefore, understanding pulmonary epithelial transport could be important for
      successful design of novel inhaled medicines. To enhance understanding of
      pulmonary epithelial transport, drug transport data were generated for a set of
      inhaled compounds (n = 10) in the single-pass, isolated perfused rat lung model.
      A compartmental in silico model was used to estimate pulmonary permeability and
      tissue retention. The theoretical model was also used to re-analyze previously
      obtained historical drug transport data from the isolated perfused lung (n = 10)
      with re-circulating buffer. This was performed to evaluate the re-circulating
      model for assessing tissue retention measurements and to increase the number of
      data points. The tissue retention was an important parameter to estimate to be
      able to describe the drug transport profiles accurately of most of the
      investigated compounds. A relationship between the pulmonary permeability and the
      intrinsic (carrier-mediated transport inhibited) permeability of Caco-2 cell
      monolayers (n = 1-6) was also established. This correlation (R2 = 0.76, p <
      .0001) suggests that intrinsic Caco-2 permeability measurements could offer early
      predictions of the passive transcellular permeability of lung epithelium to
      candidate drugs. Although, for some compounds a deviation from the correlation
      suggests that other transport mechanisms may coexist. The compartmental in silico
      model was successful in describing the pulmonary drug transport profiles of the
      investigated compounds and has potential for further development to investigate
      the effects of formulations with different features on the pulmonary overall
      absorption rate.

PMID- 29191717
TI  - Improved in vitro models for preclinical drug and formulation screening focusing
      on 2D and 3D skin and cornea constructs.
AB  - The present overview deals with current approaches for the improvement of in
      vitro models for preclinical drug and formulation screening which were elaborated
      in a joint project at the Center of Pharmaceutical Engineering of the TU
      Braunschweig. Within this project a special focus was laid on the enhancement of
      skin and cornea models. For this reason, first, a computation-based approach for
      in silico modeling of dermal cell proliferation and differentiation was
      developed. The simulation should for example enhance the understanding of the
      performed 2D in vitro tests on the antiproliferative effect of hyperforin. A
      second approach aimed at establishing in vivo-like dynamic conditions in in vitro
      drug absorption studies in contrast to the commonly used static conditions. The
      reported Dynamic Micro Tissue Engineering System (DynaMiTES) combines the
      advantages of in vitro cell culture models and microfluidic systems for the
      emulation of dynamic drug absorption at different physiological barriers and,
      later, for the investigation of dynamic culture conditions. Finally,
      cryopreserved shipping was investigated for a human hemicornea construct. As the
      implementation of a tissue-engineering laboratory is time-consuming and cost
      intensive, commercial availability of advanced 3D human tissue is preferred from
      a variety of companies. However, for shipping purposes cryopreservation is a
      challenge to maintain the same quality and performance of the tissue in the
      laboratory of both, the provider and the customer.

PMID- 29191718
TI  - "How nationality influences Opinion": Darwinism and palaeontology in France (1859
      1914).
AB  - This paper discusses the "non-reception" of Darwin's works and concepts in French
      palaeontology and palaeoanthropology between 1859 and 1914. Indeed, this
      integration was difficult, biased and belated, for ideological, intellectual and
      epistemological reasons: Clemence Royer's biased 1862 translation of Darwin's
      Origin of Species pulled its ideas toward "social darwinism", making them less
      attractive to the natural sciences. - French nationalism and the authority of
      religion, which imposed Cuvier's thinking until late into the century - the
      dominance of Lamarckian and neo-Lamarckian transformism in France, both in
      biology and in paleontology, which proposed the notion of orthogenetic laws and
      environmental determinations, and refused darwinian evolutionary mechanisms -
      obstacles inherent to the application of Darwin's concepts to palaeontology,
      namely the impossibility to identify evolutionary mechanisms through the fossil
      record, which was stressed by Darwin himself and underlined in turn by 19th
      century French palaeontologists. However, as I argue, in the course of the
      examined period, French palaeontology grew from refusal to a better understanding
      and evaluation of Darwin's thinking. The quest for intermediary forms, the
      construction of branching evolutionary trees and the attempts to reconstruct
      human biological and cultural evolution were important efforts toward an
      integration of some aspects of Darwinian views and practices into French
      palaeontology and plaeoanthropology. The 1947 Paris conference which brought
      together American Neo-darwinists and French paleontologists made Darwinian
      concepts better understood and triggered a revival of French palaeontology from
      the 1960s.

PMID- 29191719
TI  - JAK/STAT - Emerging Players in Metabolism.
AB  - The Janus kinase (JAK)/signal transducer and activator of transcription (STAT)
      pathway is crucial for transducing signals from a variety of metabolically
      relevant hormones and cytokines including growth hormone, leptin, erythropoietin,
      IL4, IL6 and IFNgamma. A growing body of evidence suggests that this pathway is
      dysregulated in the context of obesity and metabolic disease. Recent development
      of animal models has been instrumental in identifying the role of JAK/STAT
      signaling in the peripheral metabolic organs including adipose, liver, muscle,
      pancreas, and the immune system. In this review we summarize current knowledge
      about the function of JAK/STAT proteins in the regulation of metabolism, and
      highlight new potential therapeutic targets for the treatment of obesity and
      diabetes.

PMID- 29191720
TI  - Associations of ABCB1 gene polymorphisms with aripiprazole-induced autonomic
      nervous system dysfunction in schizophrenia.

PMID- 29191721
TI  - Changes in the Use of Intensive and Supportive Procedures for Patients With
      Stroke in Taiwan in the Last Month of Life Between 2000 and 2010.
AB  - CONTEXT: Stroke is the second leading cause of death and the primary cause of
      disability worldwide. It is uncertain what care patients with stroke receive in
      their end of life and what trends in care are in recent years. OBJECTIVES: The
      objective of this study was to investigate the changes in the use of intensive
      and supportive procedures for Taiwanese patients with stroke in their last month
      of life during 2000-2010. METHODS: Analysis of claims data of 55,930 patients
      with stroke obtained from the National Health Insurance Research Database was
      performed to investigate the changes in the use of intensive and supportive
      procedures for Taiwanese patients with stroke in their last month of life during
      2000-2010. RESULTS: Over the whole study period, 25.4% of patients with stroke
      were admitted to intensive care units in their last month of life. The
      percentages of patients receiving mechanical ventilation (77.4%-67.9%),
      cardiopulmonary resuscitation (53.8%-35.8%), and inotropic agents (73.5%-64.3%)
      decreased over time. The percentages of patients receiving artificial hydration
      and nutrition (65.9%-73.3%) and sedative or analgesic agents (34.7%-38.6%)
      increased over time. Patients under 85 years old were more likely to be admitted
      to intensive care units. Men were more likely to receive mechanical ventilation
      and cardiopulmonary resuscitation than women. CONCLUSION: Over time, the use of
      supportive procedures increased, and the use of intensive procedures decreased in
      patients with stroke in the last month of life. This study highlights a need for
      research, guidelines, and training in how to provide palliative care for end
      stage patients with stroke.

PMID- 29191722
TI  - Early Palliative Care in Patients With Hematological Malignancies: Where Do We Go
      From Here?

PMID- 29191723
TI  - Botulinum Toxin for Painful Torticollis in Leptomeningeal Disease: Case Report.

PMID- 29191724
TI  - Moral Distress at the End of a Life: When Family and Clinicians Do Not Agree on
      Implantable Cardioverter-Defibrillator Deactivation.
AB  - A 63-year-old man with end-stage ischemic cardiomyopathy presented with incessant
      ventricular tachycardia. He had been hospitalized multiple times in the past year
      for severe heart failure. As he approached end of life and was regularly
      receiving defibrillator shocks, his care team recommended deactivation of his
      implantable cardioverter-defibrillator. However, his family did not wish to allow
      deactivation, reporting a religious obligation to prolong his life, regardless of
      the risk of suffering. The patient was unable to adequately participate in the
      decision-making process. An implantable cardioverter-defibrillator can serve to
      avoid sudden death but may lead to a prolonged death from heart failure. This
      possibility forces the examination of values regarding prolongation of life,
      sometimes producing disagreement among stakeholders. Although ethical consensus
      holds that defibrillator deactivation is legal and ethical, disagreements about
      life prolongation may complicate decision making. The ethical, technical, and
      medical complexity involved in this case speaks to the need for clear,
      prospective communication involving the patient, the patient's family, and
      members of the care team.

PMID- 29191725
TI  - Bonding in neonatal intensive care units: Experiences of extremely preterm
      infants' mothers.
AB  - BACKGROUND: The birth of an extremely preterm infant can disrupt normal mother
      infant physical contact and the care provided by the mother. This situation has
      an impact on the process of bonding between the mother and the child. AIM: The
      objective of this study was to describe and understand the experiences of mothers
      who have extremely preterm infants admitted in Neonatal Intensive Care Units with
      regard to their bonding process. METHODS: An interpretive, qualitative research
      methodology using Gadamer's philosophical hermeneutics was carried out. A focus
      group and eleven in-depth, semi-structured interviews were conducted. Data were
      collected between June and September of 2016. FINDINGS: Sixteen women with a mean
      age of 34.4 years participated in the study. Two themes emerged from the data
      analysis: (1) premature labour and technological environment, a distorted
      motherhood, with the subthemes 'feeling of emptiness and emotional crisis' and
      'the complexity of the environment and care generate an emotional swing'; (2)
      learning to be the mother of an extremely preterm infant, with the subthemes "the
      difficulty of relating to a stranger" and 'forming the bond in spite of
      difficulties'. CONCLUSIONS: The bonding with extremely preterm infants is
      interrupted after giving birth. The maternal emotional state and the environment
      of the neonatal intensive care unit limit its development. Nursing care can
      facilitate mother-infant bonding by encouraging communication, participation in
      care, massaging or breastfeeding.

PMID- 29191726
TI  - Essential oils of culinary herbs and spices display agonist and antagonist
      activities at human aryl hydrocarbon receptor AhR.
AB  - Essential oils (EOs) of culinary herbs and spices are used to flavor, color and
      preserve foods and drinks. Dietary intake of EOs is significant, deserving an
      attention of toxicologists. We examined the effects of 31 EOs of culinary herbs
      and spices on the transcriptional activity of human aryl hydrocarbon receptor
      (AhR), which is a pivotal xenobiotic sensor, having also multiple roles in human
      physiology. Tested EOs were sorted out into AhR-inactive ones (14 EOs) and AhR
      active ones, including full agonists (cumin, jasmine, vanilla, bay leaf), partial
      agonists (cloves, dill, thyme, nutmeg, oregano) and antagonists (tarragon,
      caraway, turmeric, lovage, fennel, spearmint, star anise, anise). Major
      constituents (>10%) of AhR-active EOs were studied in more detail. We identified
      AhR partial agonists (carvacrol, ligustilide, eugenol, eugenyl acetate, thymol,
      ar-turmerone) and antagonists (trans-anethole, butylidine phtalide, R/S-carvones,
      p-cymene), which account for AhR-mediated activities of EOs of fennel, anise,
      star anise, caraway, spearmint, tarragon, cloves, dill, turmeric, lovage, thyme
      and oregano. We also show that AhR-mediated effects of some individual
      constituents of EOs differ from those manifested in mixtures. In conclusion, EOs
      of culinary herbs and spices are agonists and antagonists of human AhR, implying
      a potential for food-drug interactions and interference with endocrine pathways.

PMID- 29191727
TI  - Stable PEG-coated silver nanoparticles - A comprehensive toxicological profile.
AB  - The present study was purported to assess the toxicological profile of bare and
      polyethylene glycol (PEG) coated spherical silver nanoparticles (AgNPs) by means
      of in vitro (on human keratinocytes - HaCat cells) and in vivo non-invasive tests
      (after intraperitoneal - i.p. administration to mice). Bare and PEG-coated AgNPs
      were synthesized by applying Turkevich's method slightly modified. The physico
      chemical characterization revealed the formation of stable, spherical AgNPs and
      PEG-AgNPs, with narrow size distributions and mean hydrodynamic sizes in the
      range of 19 nm and 50 nm, respectively. Toxicity data revealed a dose-dependent
      safe profile for low concentrations of test compounds (<10 MUM) in terms of cell
      viability, whereas higher concentrations were associated with a high rate of cell
      mortality. In vivo acute/subacute toxicity data showed no denotive changes in
      mice health status after i.p. administration. Histological observations of
      internal organs and the biochemical parameters analyzed together with the other
      biological observations showed a low toxicity level with no major differences
      related to control, albeit at skin level a reduced number of mast cells was
      detected. All these observations provide strong support for the idea that coated
      silver nanoparticles could be applied as targeted nanocarriers for skin
      pathologies and diagnostic.

PMID- 29191728
TI  - The sp2-iminosugar glycolipid 1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin
      (DSO2-ONJ) as selective anti-inflammatory agent by modulation of hemeoxygenase-1
      in Bv.2 microglial cells and retinal explants.
AB  - Neuroinflammation is an early event during diabetic retinopathy (DR) that impacts
      the dynamics of microglia polarization. Gliosis is a hallmark of DR and we have
      reported the beneficial effects of 1R-DSO-ONJ, a member of the sp2-iminosugar
      glycolipid (sp2-IGL) family, in targeting microglia and reducing gliosis in
      diabetic db/db mice. Herein, we analyzed the effect of DSO2-ONJ, another family
      compound incorporating a sulfone group that better mimics the phosphate group of
      phosphatidylinositol ether lipid analogues (PIAs), in Bv.2 microglial cells
      treated with bacterial lipopolysaccaride (LPS) and in retinal explants from db/db
      mice. In addition to decreasing iNOS and inflammasome activation, the anti
      inflammatory effect of DSO2-ONJ was mediated by direct p38alpha MAPK activation.
      Computational docking experiments demonstrated that DSO2-ONJ binds to p38alpha
      MAPK at the same site where PIAs and the alkyl phospholipid perifosine activators
      do, suggesting similar mechanism of action. Moreover, treatment of microglial
      cells with DSO2-ONJ increased both heme-oxygenase (HO)-1 and Il10 expression
      regardless the presence of LPS. In retinal explants from db/db mice, DSO2-ONJ
      also induced HO-1 and reduced gliosis. Since IL-10-mediated induction of HO-1
      expression is mediated by p38alpha MAPK activation, our results suggest that this
      molecular mechanism is involved in the anti-inflammatory effects of DSO2-ONJ in
      microglia.

PMID- 29191729
TI  - Hardness and posting of foot orthoses modify plantar contact area, plantar
      pressure, and perceived comfort when cycling.
AB  - OBJECTIVES: To evaluate the effects of hardness and posting of orthoses on
      plantar profile and perceived comfort and support during cycling. DESIGN: A
      repeated measures study with randomised order of orthoses, hardness, and posting
      conditions. METHODS: Twenty-three cyclists cycled at a cadence of 90rpm and a
      perceived exertion rating of twelve. Contoured soft and hard orthoses with or
      without a medial forefoot or lateral forefoot post were evaluated. Plantar
      contact area, mean pressure and peak pressure were measured for nine plantar
      regions using the pedar(r)-X system and represented as a percentage of the total
      (CA%, MP%, and PP% respectively). Perceived comfort and support was rated on a
      visual analogue scale. RESULTS: The softer orthosis significantly increased CA%
      (p=0.014) across the midfoot and heel with a decrease in the toe region and
      forefoot. MP% (p=0.034) and PP% (p=0.012) were significantly increased at the mid
      and lateral forefoot with reductions in MP% at the midfoot and in PP% at the
      hallux and toes. Forefoot posting significantly increased CA% (p=0.018) at the
      toes and forefoot and decreased it at the heel. PP% was significantly altered
      (p=0.013) based on posting position. Lateral forefoot posting significantly
      decreased heel comfort (p=0.036). CONCLUSION: When cycling, a soft, contoured
      orthosis increased contact across the midfoot and heel, modulating forefoot and
      midfoot plantar pressures but not altering comfort or support. Forefoot postings
      significantly modified contact areas and plantar pressures and reduced comfort at
      the heel.

PMID- 29191730
TI  - Clinical Outcome of Isolated Tricuspid Regurgitation in Patients with Preserved
      Left Ventricular Ejection Fraction and Pulmonary Hypertension.
AB  - BACKGROUND: The outcome of tricuspid regurgitation (TR) remains unclear because
      of heterogeneity of etiology and the contradictory results of outcome studies.
      The aim of this study was to evaluate the clinical outcomes of TR in patients
      with pulmonary hypertension (PH) and normal left systolic function, stratified to
      patients with post- or precapillary PH. METHODS: In patients with no left valvar
      disease (isolated) functional TR, preserved left systolic function (ejection
      fraction >= 50%), and PH (systolic pulmonary pressure > 50 mm Hg), TR was
      assessed both qualitatively (grade) and semiquantitatively using the vena
      contracta method, and retrospective analysis of long-term outcomes was conducted.
      Patients with severe comorbid diseases were excluded. RESULTS: The study included
      245 patients (age 80.5 years, 37% men, ejection fraction 57%, all with pulmonary
      systolic pressure > 50 mm Hg). At least moderate to severe TR was diagnosed in
      178 patients, and their outcomes were compared with those of 67 patients with the
      same characteristics and less than mild TR. At least moderate to severe TR was
      associated with lower survival, independent of all characteristics, right
      ventricular size or function, comorbidity, or pulmonary pressure (P = .03 for
      grade and P = .02 for vena contracta). Cox proportional-hazard analysis with
      interaction terms for TR severity and etiology of PH (post- vs precapillary)
      showed that the etiology of PH did not affect the association of TR with outcome
      (P = .90 for the interaction term). CONCLUSIONS: At least moderate to severe
      isolated TR is independently associated with excess mortality in patients with
      preserved systolic function and PH, warranting heightened attention to diagnosis
      and grading. This is irrespective of etiology (pre- or postcapillary) of PH.
      Semiquantitative assessment of TR by vena contracta is an independent associate
      of outcome, superior to standard qualitative assessment.

PMID- 29191731
TI  - Characteristic Morphologies of the Bicuspid Aortic Valve in Patients with Genetic
      Syndromes.
AB  - BACKGROUND: In patients with bicuspid aortic valve (BAV), complications including
      progressive aortic stenosis and aortic dilatation develop over time. The
      morphology of cusp fusion is one of the determinants of the type and severity of
      these complications. We present the association of morphology of cusp fusion in
      BAV patients with distinctive genetic syndromes. METHODS: The Mayo Clinic
      echocardiography database was retrospectively reviewed to identify patients (age
      <= 22 years) diagnosed with BAV from 1990 to 2016. Cusp fusion morphology was
      determined from the echocardiographic studies, while coexisting cardiac defects
      and genetic syndromes were determined from chart review. RESULTS: A total of
      1,037 patients with BAV were identified: 550 (53%) had an isolated BAV, 299 (29%)
      had BAV and a coexisting congenital heart defect, and 188 (18%) had BAV and a
      coexisting genetic syndrome or disorder. There were no differences in
      distribution of morphology across the three groups. However, right-noncoronary
      (RN) cusp fusion was the predominant morphology associated with Down syndrome (P
      = .002) and right-left (RL) cusp fusion was the predominant morphology associated
      with Turner syndrome (P = .02), DiGeorge syndrome (P = .02), and Shone syndrome
      (P = .0007), when compared with valve morphology in patients with isolated BAV.
      Isolated BAV patients with RN cusp fusion had larger ascending aorta diameter (P
      = .001) and higher number of patients with >= moderate aortic regurgitation (P =
      .02), while those with RL cusp fusion had larger sinus of Valsalva diameter (P =
      .0006). CONCLUSIONS: Morphological subtypes of BAV are associated with different
      genetic syndromes, suggesting distinct perturbations of developmental pathways in
      aortic valve malformation.

PMID- 29191732
TI  - Quantification of Aortic Valve Regurgitation by Pulsed Doppler Examination of the
      Left Subclavian Artery Velocity Contour: A Validation Study with Cardiovascular
      Magnetic Resonance Imaging.
AB  - BACKGROUND: Reflux of the aortic regurgitation (AR) causes an increased diastolic
      reverse flow in the aorta and its branching vessels. We aimed to evaluate the
      feasibility and accuracy of Doppler measurements in the left subclavian artery
      (LSA) for quantification of AR in a cardiovascular magnetic resonance imaging
      (CMR) validation study. METHODS: Systolic and diastolic flow profiles of the LSA
      (subclavicular approach) were evaluated prospectively by use of pulsed wave
      Doppler in 59 patients (55.5 +/- 15 years; 44 men), 47 with a wide spectrum of AR
      and 12 as control group. Using CMR phase-contrast sequences (performed 1 cm above
      the aortic valve), the AR was divided into three groups: mild, regurgitant
      fraction (RF) < 20% (n = 17); moderate, RF 20%-40% (n = 10); and severe, RF > 40%
      (n = 20). The LSA Doppler-derived RF was calculated as the ratio between
      diastolic and systolic velocity-time integrals (VTI). RESULTS: Quality LSA
      Doppler signal could be obtained in all cases. Patients with CMR severe AR had
      higher values of LSA Doppler-derived RF (51% +/- 9% vs 36% +/- 11% vs 16% +/- 8%;
      P < .0001). LSA Doppler showed a good correlation with CMR, with a sensitivity of
      95%, specificity of 89%, and diagnostic accuracy for severe AR of 91.5%. Finally,
      Bland-Altman plots showed agreement in the group with moderate to severe AR (mean
      bias = -2.2% +/- 8%, 95% CI, -17.7 to 13.3; P = .145) but differed in mild AR.
      CONCLUSIONS: Measurements of the RF for quantification of AR using LSA Doppler
      are comparable to those of CMR, highlighting the potential role of LSA Doppler as
      an adjunctive technique to assess the severity of AR.

PMID- 29191734
TI  - Splenomegaly: Pathophysiological bases and therapeutic options.
AB  - The spleen is the largest immune organ in the human body and is also essential
      for red blood cell homeostasis and iron recycling. An average human spleen is
      approximately 10 centimetres in length and weighs 150g. Pathological conditions
      can result in the spleen weighing in excess of 2000g and extending over 30
      centrimetres in length. This remarkable property of the spleen to expand is
      termed splenomegaly. Splenomegaly can occur as a physiological response to stress
      or as a chronic process that is often detrimental to the wellbeing of the
      individual. Here, we will discuss the normal function and physiology of the
      spleen, the pathophysiological bases of splenomegaly and the commonly available
      therapeutic options. Additionally we will address experimental systems to
      determine the regulatory mechanisms underlying splenomegaly.

PMID- 29191735
TI  - First trimester serum afamin concentrations are associated with the development
      of pre-eclampsia and gestational diabetes mellitus in pregnant women.
AB  - OBJECTIVE: Aim of this study was to assess the prognostic capability of afamin to
      predict pregnancy complications. METHOD: First-trimester screening was
      consecutively performed in 4948 pregnant women, of whom 474 women developed
      pregnancy complications [gestational hypertension (n=84), pre-eclampsia (n=30),
      intrauterine growth restriction (n=107), preterm birth (n=44), and gestational
      diabetes mellitus (n=209)]. To each woman with pregnancy complications an
      uncomplicated pregnancy was matched for body mass index. Afamin serum
      concentrations were measured in 948 pregnant women at the first-trimester
      screening. RESULTS: Median afamin concentrations were significantly higher in
      women developing pre-eclampsia or gestational diabetes mellitus when compared to
      women with uncomplicated pregnancies (76mg/L vs. 65mg/L, p=0.001 and 80mg/L vs.
      69mg/L, p<0.001). There was no difference in median afamin values between all
      other pregnancy complications and their matched controls. Increased afamin (i.e.
      >65mg/L) was a strong and independent predictor for the development of pre
      eclampsia (risk ratio, 24.58; 95%CI, 2.82-214.12; p=0.004) as well as gestational
      diabetes mellitus (risk ratio, 2.07; 95%CI, 1.33-3.22; p=0.001). CONCLUSION: In
      this large nested case-control study increased afamin concentrations were a
      strong and independent predictor for pre-eclampsia and gestational diabetes
      mellitus, suggesting a potential role of afamin as predictive marker for
      pregnancy-related metabolic disorders.

PMID- 29191736
TI  - Immunogenicity of Vibrio cholerae outer membrane vesicles secreted at various
      environmental conditions.
AB  - Cholera is caused by toxigenic Vibrio cholerae. It is a significant health
      problem and an important cause of mortality of children in developing countries.
      Annually, about 5-7 million people are being infected worldwide, leading to death
      of 100,000 to 120,000. Immunization using the currently available cholera
      vaccines has been recommended by World Health Organization (WHO) in areas where
      cholera is endemic or at risk of outbreaks. Gram-negative bacteria secrete outer
      membrane vesicles (OMVs) that play important roles in virulence and host-pathogen
      interaction. The content of protein and lipid in OMVs are affected by
      purification methods and bacterial growth condition. OMVs released from V.
      cholerae are an appropriate candidate for vaccine development. The protection
      conferred by a new vaccine candidate prepared using different methods and in two
      different growth conditions with nanoparticles in an experimental model of
      cholera in mice was investigated. OMVs were encapsulated in chitosan
      tripolyphosphate (TPP) nanoparticles prepared by an ionic gelation method and
      coated with Eudragit as an enteric polymer. OMVs loaded into nanoparticles (NP
      OMVs) were homogeneous and spherical in shape, with a size of 417nm. BALB/c mice
      (male, 20-24g) were immunized via intraperitoneal (10ug) or oral route (50ug)
      with free or encapsulated OMVs. Seventy-eight days after first administration,
      serum of mice was infected with infection dose of V. cholerae (>=107 CFU). The
      new vaccine was able to protect fully against infection when it was administered
      via mucosa. By intraperitoneal route, the unpolymerized OMVs increased the
      protection against these bacteria.

PMID- 29191733
TI  - tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: Location,
      location, location.
AB  - Although tRNAs participate in the essential function of protein translation in
      the cytoplasm, tRNA transcription and numerous processing steps occur in the
      nucleus. This subcellular separation between tRNA biogenesis and function
      requires that tRNAs be efficiently delivered to the cytoplasm in a step termed
      "primary tRNA nuclear export". Surprisingly, tRNA nuclear-cytoplasmic traffic is
      not unidirectional, but, rather, movement is bidirectional. Cytoplasmic tRNAs are
      imported back to the nucleus by the "tRNA retrograde nuclear import" step which
      is conserved from budding yeast to vertebrate cells and has been hijacked by
      viruses, such as HIV, for nuclear import of the viral reverse transcription
      complex in human cells. Under appropriate environmental conditions cytoplasmic
      tRNAs that have been imported into the nucleus return to the cytoplasm via the
      3rd nuclear-cytoplasmic shuttling step termed "tRNA nuclear re-export", that
      again is conserved from budding yeast to vertebrate cells. We describe the 3
      steps of tRNA nuclear-cytoplasmic movements and their regulation. There are
      multiple tRNA nuclear export and import pathways. The different tRNA nuclear
      exporters appear to possess substrate specificity leading to the tantalizing
      possibility that the cellular proteome may be regulated at the level of tRNA
      nuclear export. Moreover, in some organisms, such as budding yeast, the pre-tRNA
      splicing heterotetrameric endonuclease (SEN), which removes introns from pre
      tRNAs, resides on the cytoplasmic surface of the mitochondria. Therefore, we also
      describe the localization of the SEN complex to mitochondria and splicing of pre
      tRNA on mitochondria, which occurs prior to the participation of tRNAs in protein
      translation. This article is part of a Special Issue entitled: SI: Regulation of
      tRNA synthesis and modification in physiological conditions and disease edited by
      Dr. Boguta Magdalena.

PMID- 29191737
TI  - Immunogenic response in obese patients undergoing rabies post-exposure
      prophylaxis with combined equine rabies immunoglobulin and rabies vaccination.
AB  - BACKGROUND: Obesity is a risk factor for increased morbidity and mortality
      associated with many vaccine preventable infectious diseases such as influenza.
      Moreover, higher volume of passive rabies immunoglobulin (RIG) due to weight
      based dosing might suppress vaccine-induced immune responses in obese patients.
      This study aimed to evaluate the effect of obesity on humoral immune responses to
      combined equine RIG and rabies vaccine treatment among patients with WHO category
      III exposure to a rabies suspected animal. METHODS: A single centre, prospective,
      open-labelled study among WHO category III rabies exposed patients was conducted
      to compare serum rabies virus neutralizing antibody (RVNA) responses measured by
      rapid fluorescent focus inhibition test between obese (body mass index, BMI > 30
      kg/m2) and control (BMI < 25 kg/m2) patients after combined immunization with
      equine rabies immunoglobulin and purified chick-embryo cell rabies vaccine for
      post exposure prophylaxis treatment. RESULTS: Post-vaccination geometric mean
      titer (GMT) of RVNA concentrations between two groups at day 7 were 0.33 (95% CI:
      0.23, 0.46) vs 0.39 (95% CI: 0.27, 0.55), 4.61 (95% CI: 3.20, 6.63) vs 3.78 (95%
      CI: 2.77, 5.16) at day 14, and 7.45 (95% CI: 5.86, 9.49) vs 5.93 (95%CI: 4.46
      7.90) at day 28 for obese and control patients, respectively. There was no
      statistically significant difference of RVNA GMT between two groups.
      Seroconversion to at least adequate concentration (RVNA titer >=0.5 IU/mL) rates
      were 34% at day 7 and 100% at days 14 and 28 in both groups. There were no
      immediate hypersensitivity reaction and no serious adverse events observed during
      the study period. CONCLUSIONS: There was no evidence of immunosuppression of
      antibodies' responses in obese patients. Combined ERIG and rabies virus
      vaccination for post exposure treatment is safe.

PMID- 29191738
TI  - Efficacy and safety of simultaneous vaccination with two modified live virus
      vaccines against porcine reproductive and respiratory syndrome virus types 1 and
      2 in pigs.
AB  - The objective of the study was to compare responses of pigs vaccinated with a
      PRRS MLV vaccine against PRRSV-1 or PRRSV-2 with the responses of pigs vaccinated
      simultaneously with both vaccines. Furthermore, the efficacy of the two PRRSV MLV
      vaccination strategies was assessed following challenge. The experimental design
      included four groups of 4-weeks old SPF-pigs. On day 0 (DPV0), groups 1-3 (N=18
      per group) were vaccinated with modified live virus vaccines (MLV) containing
      PRRSV-1 virus (VAC-T1), PRRSV-2 virus (VAC-T2) or both (VAC-T1T2). One group was
      left unvaccinated (N=12). On DPV 62, the pigs from groups 1-4 were mingled in new
      groups and challenged (DPC 0) with PRRSV-1, subtype 1, PRRSV-1, subtype 2 or
      PRRSV-2. On DPC 13/14 all pigs were necropsied. Samples were collected after
      vaccination and challenge. PRRSV was detected in all vaccinated pigs and the
      majority of the pigs were positive until DPV 28, but few of the pigs were still
      viremic 62 days after vaccination. Virus was detected in nasal swabs until DPV 7
      14. No overt clinical signs were observed after challenge. PRRSV-2 vaccination
      resulted in a clear reduction in viral load in serum after PRRSV-2 challenge,
      whereas there was limited effect on the viral load in serum following challenge
      with the PRRSV-1 strains. Vaccination against PRRSV-1 had less impact on viremia
      following challenge. The protective effects of simultaneous vaccination with
      PRRSV Type 1 and 2 MLV vaccines and single PRRS MLV vaccination were comparable.
      None of the vaccines decreased the viral load in the lungs at necropsy. In
      conclusion, simultaneous vaccination with MLV vaccines containing PRRSV-1 and
      PRRSV-2 elicited responses comparable to single vaccination and the commercial
      PRRSV vaccines protected only partially against challenge with heterologous
      strains. Thus, simultaneous administration of the two vaccines is an option in
      herds with both PRRSV types.

PMID- 29191739
TI  - Addition of C3d-P28 adjuvant to a rabies DNA vaccine encoding the G5 linear
      epitope enhances the humoral immune response and confers protection.
AB  - Rabies DNA vaccines based on full-length glycoprotein (G) induce virus
      neutralizing antibody (VNA) responses and protect against the virus challenge.
      Although conformational epitopes of G are the main target of VNAs, some studies
      have shown that a polypeptide linear epitope G5 is also able to induce VNAs.
      However, a G5 DNA vaccine has not been explored. While multiple doses of DNA
      vaccines are required in order to confer a protective immune response, this could
      be overcome by the inclusion of C3d-P28, a molecular adjuvant is know to improve
      the antibody response in several anti-viral vaccine models. To induce and enhance
      the immune response against rabies in mice, we evaluated two DNA vaccines based
      on the linear epitope G5 of Rabies Virus (RABV) glycoprotein (pVaxG5 vaccine) and
      another vaccine consisting of G5 fused to the molecular adjuvant C3d-P28 (pVaxF1
      vaccine). VNA responses were measured in mice immunized with both vaccines. The
      VNA levels from the group immunized with pVaxG5 decreased gradually, while those
      from the group vaccinated with pVaxF1 remained high throughout the experimental
      study. After challenge with 22 LD50 of the Challenge Virus Strain (CVS), the
      survival rate of mice immunized with pVaxG5 and pVaxF1 was increased by 27% and
      50% respectively, in comparison to the PBS group. Furthermore, the in vitro
      proliferation of anti-rabies specific spleen CD4+ and CD8+ T cells from mice
      immunized with pVaxF1 was observed. Collectively, these results suggest that the
      linear G5 epitope is a potential candidate vaccine. Furthermore, the addition of
      a C3d-P28 adjuvant contributed to enhanced protection, the sustained production
      of VNAs, and a specific T-cell proliferative response.

PMID- 29191740
TI  - Influence of Prior Nicotine and Alcohol Use on Functional Outcome in Patients
      after Intracerebral Hemorrhage.
AB  - BACKGROUND: The influence of prior nicotine or alcohol use (legal drug use [LDU])
      on outcome measures after intracerebral hemorrhage (ICH) is insufficiently
      established. We investigated drug-specific associations with (1) neuroradiologic
      and clinical parameters and (2) functional long-term outcome after ICH. METHODS:
      This observational cohort study analyzed consecutive spontaneous patients with
      ICH (n = 554) from our prospective institutional registry over a 5-year study
      period (January 2010 to December 2014). We compared no-LDU patients with LDU
      patients, and patients using only nicotine, only alcohol, or both. To account for
      baseline imbalances, we reanalyzed cohorts after propensity score matching.
      RESULTS: Prevalence of prior LDU was 197 of 554 (35.6%), comprising 94 of 554
      (17.0%) with only nicotine use, 33 of 554 (6.0%) with only alcohol use, and 70 of
      554 (12.6%) with alcohol and nicotine use. LDU patients were younger (65 [56-73]
      versus 75 [67-82], P <.01), less often female (n = 61 of 197 [31.0%] versus n =
      188 of 357 [52.7%], P <.01), had more often prior myocardial infarction (n = 29
      of 197 [14.7%] versus n = 24 of 357 [6.7%], P <.01), and in-hospital
      complications (sepsis or systemic inflammatory response syndrome: n = 95 of 197
      [48.2%] versus n = 98 of 357 [27.5%], P <.01; pneumonia: n = 89 of 197 [45.2%]
      versus n = 110 of 357 [30.8%], P <.01). Except for an increased risk of pneumonia
      (odds ratio 2.22, confidence interval [1.04-4.75], P = .04) in patients using
      both nicotine and alcohol, we detected no significant differences upon reanalysis
      after propensity score matching of neuroradiologic or clinical parameters,
      complications, or long-term outcome between patients with and without LDU
      (mortality: n = 48 of 150 [32.0%] versus n = 45 of 150 [30.0%], P = .71;
      favorable outcome [modified Rankin Scale 0-3]: n = 56 of 150 [37.3%] versus n =
      53 of 150 [35.3%], P = .72). CONCLUSIONS: Prior nicotine use, alcohol use, and
      their combination were associated with significant differences in baseline
      characteristics. However, adjusting for unevenly balanced baseline parameters
      revealed no differences in functional long-term outcome after ICH.

PMID- 29191741
TI  - Thrombolytic Therapy of Acute Ischemic Stroke during Early Pregnancy.
AB  - Thrombolytic treatment (recombinant tissue plasminogen activator [rt-PA]) has
      established efficacy in acute ischemic stroke, but pregnancy has been an
      exclusion criterion for all clinical trials that validated alteplase in acute
      stroke, so our knowledge about its use in this condition is limited. Herein we
      report the successful use of intravenous rt-PA thrombolysis, uncomplicated by
      neither hemorrhage development nor other complication in a woman who was 13 weeks
      pregnant with acute ischemic stroke. The brain magnetic resonance imaging
      diffusion-weighted sequences showed increased signal in the territory of the left
      middle cerebral artery. Our case had a good maternal and fetal outcome, and
      advocates that the use of thrombolytics may be feasible in pregnant patients and
      help to avoid residual neurologic deficits. A summary of published cases in the
      early aspect of pregnancy and outcomes is presented. Risks and benefits to mother
      and fetus must be weighted up, but intravenous thrombolysis must not be
      considered as an absolute contraindication, even in early pregnancy.

PMID- 29191742
TI  - A rare case of a calcified cephalhematoma mistaken as a skull fracture.

PMID- 29191743
TI  - Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A
      case report.

PMID- 29191744
TI  - Predicting fruit and vegetable consumption in long-haul heavy goods vehicle
      drivers: Application of a multi-theory, dual-phase model and the contribution of
      past behaviour.
AB  - Fruit and vegetable intake is insufficient in industrialized nations and long
      haul heavy goods vehicle (HGV) drivers are considered a particularly at-risk
      group. The aim of the current study was to test the effectiveness of a multi
      theory, dual-phase model to predict fruit and vegetable consumption in Australian
      long-haul HGV drivers. A secondary aim was to examine the effect of past fruit
      and vegetable consumption on model paths. A prospective design with two waves of
      data collection spaced one week apart was adopted. Long-haul HGV drivers (N =
      212) completed an initial survey containing theory-based measures of motivation
      (autonomous motivation, intention), social cognition (attitudes, subjective
      norms, perceived behavioural control), and volition (action planning, coping
      planning) for fruit and vegetable consumption. One week later, participants (n =
      84) completed a self-report measure of fruit and vegetable intake over the
      previous week. A structural equation model revealed that autonomous motivation
      predicted intentions, mediated through attitudes and perceived behavioural
      control. It further revealed that perceived behavioural control, action planning,
      and intentions predicted fruit and vegetable intake, whereby the intention
      behaviour relationship was moderated by coping planning. Inclusion of past
      behaviour attenuated the effects of these variables. The model identified the
      relative contribution of motivation, social cognition, and volitional components
      in predicting fruit and vegetable intake of HGV drivers. Consistent with previous
      research, inclusion of past fruit and vegetable consumption led to an attenuation
      of model effects, particularly the intention-behaviour relationship. Further
      investigation is needed to determine which elements of past behaviour exert most
      influence on future action.

PMID- 29191745
TI  - Do nutrition labels influence healthier food choices? Analysis of label viewing
      behaviour and subsequent food purchases in a labelling intervention trial.
AB  - BACKGROUND: There are few objective data on how nutrition labels are used in real
      world shopping situations, or how they affect dietary choices and patterns.
      DESIGN: The Starlight study was a four-week randomised, controlled trial of the
      effects of three different types of nutrition labels on consumer food purchases:
      Traffic Light Labels, Health Star Rating labels, or Nutrition Information Panels
      (control). Smartphone technology allowed participants to scan barcodes of
      packaged foods and receive randomly allocated labels on their phone screen, and
      to record their food purchases. The study app therefore provided objectively
      recorded data on label viewing behaviour and food purchases over a four-week
      period. A post-hoc analysis of trial data was undertaken to assess frequency of
      label use, label use by food group, and association between label use and the
      healthiness of packaged food products purchased. RESULTS: Over the four-week
      intervention, study participants (n = 1255) viewed nutrition labels for and/or
      purchased 66,915 barcoded packaged products. Labels were viewed for 23% of all
      purchased products, with decreasing frequency over time. Shoppers were most
      likely to view labels for convenience foods, cereals, snack foods, bread and
      bakery products, and oils. They were least likely to view labels for sugar and
      honey products, eggs, fish, fruit and vegetables, and meat. Products for which
      participants viewed the label and subsequently purchased the product during the
      same shopping episode were significantly healthier than products where labels
      were viewed but the product was not subsequently purchased: mean difference in
      nutrient profile score -0.90 (95% CI -1.54 to -0.26). CONCLUSIONS: In a secondary
      analysis of a nutrition labelling intervention trial, there was a significant
      association between label use and the healthiness of products purchased.
      Nutrition label use may therefore lead to healthier food purchases.

PMID- 29191746
TI  - Proteomics analysis to understand the ABA stimulation of wound suberization in
      kiwifruit.
AB  - : Quick suberin-based healing after wounding played a protective role for plant
      to prevent further damage. In this study, the stimulative effect of exogenous
      abscisic acid (ABA) on wound suberization in postharvest kiwifruit was evaluated
      through suberin staining with toluidine blue O as well as the determination of
      suberin phenolics and aliphatics in wound tissue. Furthermore, to reveal the
      regulatory involvement of ABA in wound suberization, comparative quantitative
      proteomics and transcriptomics analyses based on iTRAQ and qRT-PCR technique were
      performed. In proteomics levels, a total of 95 protein species consistently
      showed differential abundance between ABA and control, including 29 down
      regulated and 66 up-regulated protein species. The Kyoto Encyclopedia of Genes
      and Genomes (KEGG) with protein-protein interaction analyses revealed that ABA
      mainly affected the antioxidant system, phenylpropanoid metabolism and lipid
      metabolism associated with wound suberization. Based on the data of proteomics
      analysis, the differential expressions of genes encoding 11 selected protein
      species were confirmed by qRT-PCR analyses. GSH-Px, MDHAR, SOD, APX, POD, PAL,
      CCR, PPO, CYP86B1, DGGT and KCS11 were likely to be the key enzymes that involved
      the response of ABA to stimulate wound suberization by mediating the antioxidant
      system, phenylpropanoid metabolism and lipid metabolism. BIOLOGICAL SIGNIFICANCE:
      Kiwifruit is susceptible to physical injury causing postharvest deterioration
      during harvest, transportation and storage. Therefore, quick healing is important
      for maintaining the postharvest quality of injured fruit. This work elucidated
      the potential role of ABA and the proteomic mechanism of its regulation in wound
      suberization of postharvest kiwifruit.

PMID- 29191747
TI  - Peptide fingerprinting of the sea anemone Heteractis magnifica mucus revealed
      neurotoxins, Kunitz-type proteinase inhibitors and a new beta-defensin alpha
      amylase inhibitor.
AB  - : Sea anemone mucus, due to its multiple and vital functions, is a valuable
      substance for investigation of new biologically active peptides. In this work,
      compounds of Heteractis magnifica mucus were separated by multistage liquid
      chromatography and resulting fractions were analyzed by MALDI-TOF MS. Peptide
      maps constructed according to the molecular masses and hydrophobicity showed
      presence of 326 both new and known peptides. Several major peptides from mucus
      were identified, including the sodium channel toxin RpII isolated earlier from H.
      magnifica, and four Kunitz-type proteinase inhibitors identical to H. crispa
      ones. Kunitz-type transcript diversity was studied and sequences of mature
      peptides were deduced. New beta-defensin alpha-amylase inhibitor, a homolog of
      helianthamide from Stichodactyla helianthus, was isolated and structurally
      characterized. Overall, H. magnifica is a source of biologically active peptides
      with great pharmacological potential. BIOLOGICAL SIGNIFICANCE: Proteinase and
      alpha-amylase inhibitors along with toxins are major components of H. magnifica
      mucus which play an important role in the successful existence of sea anemones.
      Obtained peptide maps create a basis for more accurate identification of peptides
      during future transcriptomic/genomic studies of sea anemone H. magnifica.

PMID- 29191748
TI  - Study of a novel agent for TCA precipitated proteins washing - comprehensive
      insights into the role of ethanol/HCl on molten globule state by multi
      spectroscopic analyses.
AB  - : Sample preparation for mass spectrometry-based proteomics is a key step for
      ensuring reliable data. In gel-free experimental workflows, protein purification
      often starts with a precipitation stage using trichloroacetic acid (TCA). In
      presence of TCA, proteins precipitate in a stable molten globule state making the
      pellet difficult to solubilize in aqueous buffer for proteolytic digestion and MS
      analysis. In this context, the objective of this work was to study the
      suitability of a novel agent, ethanol/HCl, for the washing of TCA-precipitated
      proteins. This method optimized the recovery of proteins in aqueous buffer (50 to
      96%) while current organic solvents led to losses of material. Following a
      mechanistic study, the effect of ethanol/HCl on the conformation of TCA
      precipitated proteins was investigated. It was shown that the reagent triggered
      the unfolding of TCA-stabilized molten globule into a reversible intermediate,
      characterized by a specific Raman signature, which favored protein subsequent
      resolubilization. Finally, the efficiency of ethanol/HCl for the washing of TCA
      precipitated proteins extracted from a biofilm, a soil or a mouse liver was
      demonstrated (data available via ProteomeXchange with identifier PXD008110).
      Being versatile and simple, it could be of great interest to include an
      ethanol/HCl wash-step to produce high-quality protein extracts. SIGNIFICANCE: In
      mass spectrometry-based proteomics workflows, proteins precipitation and/or
      washing usually involves the use of acetone. In fact, this solvent is effective
      for removing both biological interferences (e.g. lipids) and chemicals employed
      in protein extraction/purification protocols (e.g. TCA, SDS). However, the use of
      acetone can lead to significant protein losses. Moreover, when proteins are
      precipitated with TCA, the acetone-treated precipitate remains hard to disperse,
      leading to poor resolubilization of proteins in aqueous buffers. Here, we
      investigated the use of ethanol/HCl for washing TCA-precipitated proteins, with
      the aim to produce high-quality protein extracts which can be directly analyzed
      by LC-MS. An opening study on standard solutions showed that ethanol/HCl led to
      reduced losses of proteins compared to usual solvents (i.e. acetone and ethanol).
      This reagent also enabled a better solubilization of proteins in aqueous buffer
      that is necessary for their direct trypsin digestion and LC-HRMS analysis. A
      mechanistic study, performed through several spectroscopic analyses (LC-HRMS,
      Raman, spectrofluorometry), showed that treatment with ethanol/HCl induced
      conformational changes of TCA-precipitated proteins. Finally, we compared the
      efficiency of ethanol/HCl to published protocols for the washing of protein
      extracts from three different complex samples (i.e. soil, biofilm, and mouse
      liver). Our results demonstrated that ethanol/HCl is a valuable alternative to
      previous protein washing methods and, therefore could become a useful tool in
      mass spectrometry-based proteomics workflows for various applications (e.g.
      clinical research, chemical biology, environmental metaproteomics...).

PMID- 29191749
TI  - Design and verification of halogen-bonding system at the complex interface of
      human fertilization-related MUP PDZ5 domain with CAMK's C-terminal peptide.
AB  - Calmodulin-dependent protein kinase (CAMK) is physiologically activated in
      fertilized human oocytes and is involved in the Ca2+ response pathways that link
      the fertilization calmodulin signal to meiosis resumption and cortical granule
      exocytosis. The kinase has an unstructured C-terminal tail that can be recognized
      and bound by the PDZ5 domain of its cognate partner, the multi-PDZ domain protein
      (MUP). In the current study, we reported a rational biomolecular design of
      halogen-bonding system at the complex interface of CAMK's C-terminal peptide with
      MUP PDZ5 domain by using high-level computational approaches. Four organic
      halogens were employed as atom probes to explore the structural geometry and
      energetic property of designed halogen bonds in the PDZ5-peptide complex. It was
      found that the heavier halogen elements such as bromine Br and iodine I can
      confer stronger halogen bond but would cause bad atomic contacts and overlaps at
      the complex interface, while fluorine F cannot form effective halogen bond in the
      complex. In addition, the halogen substitution at different positions of
      peptide's aromatic ring would result in distinct effects on the halogen-bonding
      system. The computational findings were then verified by using fluorescence
      analysis; it is indicated that the halogen type and substitution position play
      critical role in the interaction strength of halogen bonds, and thus the PDZ5
      peptide binding affinity can be improved considerably by optimizing their
      combination.

PMID- 29191750
TI  - Sucrose withdrawal induces depression and anxiety-like behavior by Kir2.1
      upregulation in the nucleus accumbens.
AB  - Dieting induces depression and anxiety among other emotional symptoms. Animal
      models indicate that repeated access to palatable foods such as sugar induces
      depression and anxiety-like behavior when the food is no longer available.
      However, the neurobiological mechanisms of how dietary restriction influences
      mood have not been fully understood. We used the two-bottle sucrose choice
      paradigm as an overeating and withdrawal model. Withdrawal after lengthy sucrose
      overeating elicited depression and anxiety-like behavior, which was reversed by
      sucrose reinstatement. In the nucleus accumbens (NAc) of sucrose withdrawal
      animals, dopamine levels and cAMP response element binding protein (CREB)
      activity were significantly reduced, while the inwardly rectifying K+ channel,
      Kir2.1, was significantly elevated. In addition, overexpression of Kir2.1
      selectively in neurons expressing dopamine D1 receptors was sufficient to induce
      negative mood-linked behavior in the absence of sucrose overeating experience. As
      elevated K+ channels reduce neuronal excitability, a sucrose withdrawal-induced
      increase in Kir2.1 expression is able to decrease NAc activity, which provides a
      cellular basis for depression and anxiety-like behavior in animals.

PMID- 29191752
TI  - The use of chemogenetic approaches to study the physiological roles of muscarinic
      acetylcholine receptors in the central nervous system.
AB  - Chemical genetic has played an important role in linking specific G protein
      coupled receptor (GPCR) signalling to cellular processes involved in central
      nervous system (CNS) functions. Key to this approach has been the modification of
      receptor properties such that receptors no longer respond to endogenous ligands
      but rather can be activated selectively by synthetic ligands. Such modified
      receptors have been called Receptors Activated Solely by Synthetic Ligands
      (RASSLs) or Designer Receptors Exclusively Activated by Designer Drugs (DREADDs).
      Unlike knock-out animal models which allow detection of phenotypic changes caused
      by loss of receptor functions, RASSL and DREADD receptors offer the possibility
      of rescuing "knock-out" phenotypic deficits by administration of the synthetic
      ligands. Here we describe the use of these modified receptors in defining the
      physiological role of GPCRs and validation of receptors as drug targets. This
      article is part of the Special Issue entitled 'Neuropharmacology on Muscarinic
      Receptors'.

PMID- 29191751
TI  - Hippocampus ghrelin receptor signaling promotes socially-mediated learned food
      preference.
AB  - Social cues are potent regulators of feeding behavior, yet the neurobiological
      mechanisms through which social cues influence food intake are poorly understood.
      Here we investigate the hypothesis that the appetite-promoting gut-derived
      hormone, ghrelin, signals in the hippocampus to promote learned social aspects of
      feeding behavior. We utilized a procedure known as 'social transmission of food
      preference' (STFP) in which rats ('Observers') experience a social interaction
      with another rat ('Demonstrators') that recently consumed flavored/scented chow.
      STFP learning in Observer rats is indicated by a significant preference for the
      Demonstrator paired flavor of chow vs. a novel unpaired flavor of chow in a
      subsequent consumption choice test. Our results show that relative to vehicle
      treatment, ghrelin targeted to the ventral CA1 subregion of the hippocampus (vHP)
      enhanced STFP learning in rats. Additionally, STFP was impaired following
      peripheral injections of l-cysteine that reduce circulating ghrelin levels,
      suggesting that vHP ghrelin-mediated effects on STFP require peripheral ghrelin
      release. Finally, the endogenous relevance of vHP ghrelin receptor (GHSR-1A)
      signaling in STFP is supported by our data showing that STFP learning was
      eliminated following targeted viral vector RNA interference-mediated knockdown of
      vHP GHSR-1A mRNA. Control experiments indicate that vHP ghrelin-mediated STFP
      effects are not secondary to altered social exploration and food intake, nor to
      altered food preference learning based on nonsocial olfactory cues. Overall these
      data reveal a novel neurobiological system that promotes conditioned, social
      aspects of feeding behavior.

PMID- 29191753
TI  - Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and
      p70S6K to stimulate acute food intake.
AB  - Melanin-Concentrating Hormone (MCH) is one of the most relevant orexigenic
      factors specifically located in the lateral hypothalamic area (LHA), with its
      physiological relevance demonstrated in studies using several genetically
      manipulated mice models. However, the central mechanisms controlling MCH-induced
      hyperphagia remain largely uncharacterized. Here, we show that central injection
      of MCH in mice deficient for kappa opoid receptor (k-OR) failed to stimulate
      feeding. To determine the hypothalamic area responsible for this MCH/k-OR
      interaction, we performed virogenetic studies and found that downregulation of k
      OR by adeno-associated viruses (shOprk1-AAV) in LHA, but not in other
      hypothalamic nuclei, was sufficient to block MCH-induced food intake. Next, we
      sought to investigate the molecular signaling pathway within the LHA that
      mediates acute central MCH stimulation of food intake. We found that MCH
      activates k-OR and that increased levels of phosphorylated extracellular signal
      regulated kinase (ERK) are associated with downregulation of phospho-S6 Ribosomal
      Protein. This effect was prevented when a pharmacological inhibitor of k-OR was
      co-administered with MCH. Finally, the specific activation of the direct upstream
      regulator of S6 (p70S6K) in the LHA attenuated MCH-stimulated food consumption.
      Our results reveal that lateral hypothalamic k-OR system modulates the orexigenic
      action of MCH via the p70S6K/S6 pathway.

PMID- 29191754
TI  - Disease-modifying benefit of Fyn blockade persists after washout in mouse
      Alzheimer's model.
AB  - Alzheimer's disease remains without a disease-modifying therapy that improves
      symptoms after therapy withdrawal. Because no investigational agents have
      demonstrated disease-modifying effects clinically, we tested whether the Fyn
      inhibitor, saracatinib, provides persistent improvement in a transgenic model.
      Aged APPswe/PS1DeltaE9 mice were treated with saracatinib or memantine for 4
      weeks and spatial memory improved to control levels. After drug washout, there
      was sustained rescue of both memory function and synapse density by saracatinib,
      but a loss of benefit from memantine. These data demonstrate a disease-modifying
      persistent benefit for saracatinib in a preclinincal Alzheimer's model, and
      distinguish its action from that of memantine.

PMID- 29191756
TI  - Functional connectivity between anterior cingulate cortex and orbitofrontal
      cortex during value-based decision making.
AB  - There is a growing body of evidence showing that the anterior cingulate (ACC) and
      the orbitofrontal (OFC) cortex are both essential for reinforcement-guided
      decision making. Focusing on functional connectivity approach through coherence,
      we studied whether communication between the ACC and OFC through neural
      synchronization is a necessary stage for performing value-based decision making.
      We used a T-maze task with a differential reward (Large vs. small reward) and
      cost (long vs. short waiting time) and simultaneously recorded local field
      potentials (LFP) from the ACC and OFC. Task-dependent synchronization in
      theta/low beta (4-20 Hz) frequency bands were observed between areas when rats
      chose the higher over the lower reward. This synchronization was significantly
      poorer when rats chose lower rewards or passively performed the task. High-gamma
      (80-100 Hz) synchrony between areas was also observed, however, it was not
      dependent on the animal's decision. Our results propose that synchronization
      between the ACC and OFC in the low-frequency range is necessary during value
      based decision making.

PMID- 29191755
TI  - Pharmacological validation of voluntary gait and mechanical sensitivity assays
      associated with inflammatory and neuropathic pain in mice.
AB  - The urgent need for more effective analgesic treatment options has prompted a re
      evaluation of the behavioral tests used to assess pain in pre-clinical research,
      with an emphasis on inclusion of more voluntary, un-evoked behavioral assessments
      of pain. In order to validate voluntary gait analysis and a voluntary mechanical
      conflict-avoidance assay, we tested mouse models of neuropathy (spared nerve
      injury) and inflammation (complete Freund's adjuvant) alongside reflexive
      measures of mechanical and thermal hypersensitivity. To establish whether the
      observed changes in behavioral responses were pain-related, known analgesics
      (buprenorphine, gabapentin, carprofen) were also administered. Spared nerve
      injury persistently altered several gait indices, whereas complete Freund's
      adjuvant caused only transient changes. Furthermore, known analgesics could not
      reverse these gait changes, despite demonstrating their previously established
      efficacy in reflexive measures of mechanical and thermal hypersensitivity. In
      contrast, the mechanical conflict-avoidance assay demonstrated aversion in mice
      with neuropathy and inflammation-induced hypersensitivity, which could both be
      reversed by analgesics. We conclude that voluntary gait changes in rodent
      neuropathic and inflammatory pain models are not necessarily indicative of pain
      related adaptations. On the other hand, mechanical conflict-avoidance represents
      a valid operant assay for quantifying pain-related behaviors in mice that can be
      reversed by known analgesics.

PMID- 29191757
TI  - Does Previous Laparoscopic Experience Influence Basic Robotic Surgical Skills?
AB  - OBJECTIVE: Studies addressing the effect of laparoscopic experience on robotic
      skills have produced conflicting results. This study aimed to compare simulated
      robotic surgical tasks using the virtual reality simulator dV-Trainer between
      laparoscopically experienced surgeons and first-year surgical residents. DESIGN:
      A cross-sectional study. Participants completed 4 trials of the following tasks
      on the dV-Trainer: Peg Board 2, Ring and Rail 1, and Suture Sponge 1. Performance
      was recorded using a computerized built-in scoring algorithm. Scores and metrics
      were compared between groups 1 and 2 and between the first and subsequent trials.
      SETTING: Hospital de Clinicas, Porto Alegre, Brazil, a tertiary care teaching
      hospital. PARTICIPANTS: Twenty laparoscopically experienced surgeons (group 1)
      and 20 first-year surgical residents (group 2). All participants completed the
      study. RESULTS: The overall scores for Peg Board 2 (738.04 +/- 267.83 vs 730.39
      +/- 225.31; p  = 0.57), Ring and Rail 1 (919.03 +/- 242.69 vs 965.84 +/- 222.96;
      p  =  0.13), and Suture Sponge 1 (563.62 +/- 185.50 vs 560.99 +/- 152.71; p =
      0.67) did not differ significantly between groups 1 and 2. Group 1 had better
      results for master workspace range in Peg Board 2 and Ring and Rail 1. Group 2
      had higher scores for economy of motion in Peg Board 2 and Ring and Rail 1 and
      for excessive instrument force in Ring and Rail 1. In both groups, the overall
      scores in the third and fourth trials were significantly higher than those in the
      first trial. CONCLUSIONS: There are no significant differences in the performance
      of simulated robotic surgical tasks between laparoscopically experienced surgeons
      and laparoscopically naive surgical residents. Some slight differences were
      observed in specific metrics, but these differences were not sufficient to change
      the final results. We may assume that laparoscopic experience should not be an
      essential step in the initial learning curve of robotic surgery.

PMID- 29191758
TI  - The association between experiences with patient-centred care and health-related
      quality of life in women with endometriosis.
AB  - In this cross-sectional study, we investigated whether patient-centred
      endometriosis care (PCEC) is associated with health-related quality of life
      (HRQOL). Dutch-speaking women with endometriosis, treated by laparoscopy in a
      university clinic between 2009 and 2010, were eligible (n = 194). Endometriosis
      Health Profile-30 and ENDOCARE questionnaire were used to assess HRQOL and PCEC,
      respectively. Overall and subscale scores were converted to a scale from 0 (best
      score) to 100 (worst score). Linear regression analyses were conducted while
      controlling for confounders. Participants (n = 109) had a mean age of 35.4 years;
      79.6% had moderate-severe endometriosis. Mean scores for overall HRQOL and PCEC
      were 29.3/100 and 38.0/100, respectively. The PCEC-subscale 'continuity' was
      significantly associated with overall HRQOL (P = 0.029). A significant
      association was found between overall PCEC and the HRQOL-subscale 'social
      support' (P = 0.026). The PCEC-subscales 'information' and 'continuity' were
      significantly associated with the HRQOL-subscales 'emotional wellbeing' and
      'social support' (P < 0.05). The PCEC-subscale 'respect' was significantly
      associated with the HRQOL-subscale 'emotional wellbeing' (P = 0.023).
      Multivariable regression analyses produced no significant associations, including
      all subscales of PCEC. Providing PCEC could lead to better HRQOL, especially if
      paying attention to 'continuity', 'respect' and 'information'. Large-scale
      longitudinal research is needed.

PMID- 29191759
TI  - A novel and versatile dual fluorescent reporter tool for the study of gene
      expression and regulation in multi- and single copy number.
AB  - To unravel intricate mechanisms of gene regulation it is imperative to work in
      physiologically relevant conditions and therefore preferentially in single copy
      constructs, which are not always easy to manipulate. Such in vivo studies are
      generally based on enzymatic assays, microarrays, RNA-seq, qRT-PCR, or multicopy
      reporter gene systems, frequently with beta-galactosidase, luciferase or a
      fluorescent protein as reporter. Each method has its advantages and shortcomings
      and may require validation. Enzyme assays are generally reliable but may be quite
      complex, time consuming, and require a (expensive) substrate. Microarrays and RNA
      seq provide a genome wide view of gene expression but may rapidly become
      expensive and time consuming especially for detailed studies with large numbers
      of mutants, different growth conditions and multiple time points. Multicopy
      reporter gene systems are handy to generate numerous constructs but may not
      provide accurate information due to titration effects of trans-acting regulatory
      elements. Therefore and in spite of the existence of various reporter systems,
      there is still need for an efficient and user-friendly tool for detailed studies
      and high throughput screenings. Here we develop and validate a novel and
      versatile fluorescent reporter tool to study gene regulation in single copy mode
      that enables real-time measurement. This tool bears two independent fluorescent
      reporters that allow high throughput screening and standardization, and combines
      modern efficient cloning methods (multicopy, in vitro manipulation) with
      classical genetics (in vivo homologous recombination with a stable, self
      transmissible episome) to generate multi- and single copy reporter systems. We
      validate the system with constitutive and differentially regulated promoters and
      show that the tool can equally be used with heterologous transcription factors.
      The flexibility and versatility of this dual reporter tool in combination with an
      easy conversion from a multicopy plasmid to a stable, single copy reporter system
      makes this system unique and attractive for a variety of applications. Examples
      are in vivo studies of DNA-binding transcription factors (single copy) or
      screening of promoter and RBS libraries (multicopy) for synthetic biology
      purposes.

PMID- 29191760
TI  - Thermodynamic Estimate of the Number of Solvent Molecules Displaced by a Solute
      Molecule for Enthalpy-Driven Adsorption: Phenobarbital and Activated Carbons as
      the Model System.
AB  - A Modified Crisp Equation, describing the differential Gibbs free energy of the
      adsorption process, is being proposed, which considers multiple sites available
      on the surface for adsorption and their relative fractions. The differential
      Gibbs free energy can be calculated by the van't Hoff Equation, which depends on
      the affinity constant in the Langmuir-like equation. To consider the number of
      solvent molecules displaced by a solute molecule in the adsorption process, a new
      derivative of the Langmuir-like equation is being proposed as well. By comparing
      the differential Gibbs free energies obtained from the 2 thermodynamic
      relationships, it can be determined that a phenobarbital molecule displaces 5
      water molecules on the activated carbon surface for site-specific adsorption from
      solution. For the series of experimental conditions studied, including 4
      activated carbons, pH effects, temperature effects, and solvent effects, the
      corrected differential Gibbs free energies using n1 = 5 for site-specific
      adsorption are quite consistent between the 2 thermodynamic relationships. The
      difference between the estimates of the differential Gibbs free energies by the
      Modified Crisp Equation and the van't Hoff Equation provides a new experimental
      method to calculate the number of solvent molecules displaced by an adsorbing
      solute molecule.

PMID- 29191761
TI  - DSM-5 personality trait domains and withdrawal versus approach motivational
      tendencies in response to the perception of other people's desperation and angry
      aggression.
AB  - Expressions of affect communicate social messages, which trigger approach and
      withdrawal/avoidance motivational tendencies in the observer. The present study
      investigated relationships between inter-individual differences in the
      motivational responses to other people's affect expressions and DSM-5 personality
      trait domains. State-dependent, transient EEG alpha asymmetry responses provided
      indicators of the relative activation of withdrawal versus approach motivation in
      the respective social-emotional contexts. The Personality Inventory for the DSM-5
      (PID-5) was used for the assessment of personality traits in a non-clinical
      sample. Individuals with higher levels of Antagonism showed relative activation
      of approach versus withdrawal motivation (as indicated by less relative right
      frontal activation) in response to confrontation with auditory expressions of
      angry aggression, whereas participants with higher levels of Detachment showed
      relative activation of withdrawal versus approach motivation (as indicated by
      greater relative right frontal activation) to the perception of other people's
      desperate crying.

PMID- 29191762
TI  - APRN-Conducted Medication Reviews for Long-Stay Nursing Home Residents.
AB  - OBJECTIVE: As part of the Missouri Quality Initiative (MOQI) to reduce
      hospitalizations for long-stay nursing home residents, this article describes
      reasons MOQI advanced practice registered nurses (APRNs) recommended medication
      order changes as part of their medication review process as well as the outcomes
      of their recommendations. DESIGN: Cross-sectional descriptive study of MOQI APRN
      conducted medication reviews. SETTING: Long-stay nursing homes participating in
      the MOQI project. PARTICIPANTS: Seventeen MOQI APRNs recorded medication reviews
      for 3314 long-stay residents residing in 16 Midwestern nursing homes over a 2
      year period. INTERVENTION: APRNs conducted medication reviews and made
      recommendations for medication order changes to residents' medical providers.
      MEASUREMENTS: The MOQI medication review database was used to abstract data.
      RESULTS: There were 19,629 medication reviews recorded for 3314 residents during
      the 2-year period. Of the 19,629 reviews, 50% (n = 9841) resulted in recommended
      order changes of which 82% (n = 8037) of order changes occurred. More than two
      thirds of recommendations were because of changes in the residents' plans of
      care. Other recommendations included adjusting and/or discontinuing medications
      that had the potential for harm. CONCLUSION: Resident care needs are dynamic,
      resulting in the need for frequent medication order changes. MOQI APRNs, because
      of their advanced pharmacological education and daily presence in the nursing
      home, are uniquely positioned to ensure residents' medications aligned with their
      overall goals of care while minimizing risk of harm.

PMID- 29191763
TI  - Reliability and Validity of the Care Plan Checklist for Evidence of Person
      Centered Approaches for Behavioral and Psychological Symptoms Associated With
      Dementia.
AB  - PURPOSE: The purpose of this study was to test the reliability and validity of
      the Care Plan Checklist for Evidence of Person-Centered Approaches for Behavioral
      and Psychological Symptoms Associated with Dementia (BPSD). METHODS: This study
      used baseline data from the first cohort of a larger randomized clinical trial
      testing the implementation of the Evidence of Integration Triangle for BPSD.
      Fourteen settings volunteered to participate, 8 from Maryland and 6 from
      Pennsylvania, and a total of 137 residents were recruited. In addition to
      completing the Care Plan Checklist for Evidence of Person-Centered Approaches for
      BPSD, assessments of depressive symptoms (Cornell Scale for Depression in
      Dementia), resistiveness to care (Resistiveness to Care Scale), and agitation
      (Cohen-Mansfield Agitation Inventory) were also completed on each participant.
      Reliability was tested based on evidence of internal consistency and inter-rater
      reliability. Construct validity was tested using a Rasch measurement model to
      determine item fit and hypothesis testing using bivariate correlations. Item
      mapping was also performed. RESULTS: The majority of the sample was female (69%),
      Caucasian (69%), non-Hispanic (98%), and not married (78%). The mean age of the
      sample was 82.01 years (standard deviation = 11.44). There was evidence of
      reliability based on internal consistency with a Cronbach alpha of 0.96 and inter
      rater reliability with correlations between 2 evaluators of r = 0.93, P = .001.
      There was evidence of validity of the scale based on item fit as the infit
      statistics and outfit statistics were all within the acceptable range with the
      exception of the outfit statistic for the item focused on sexually inappropriate
      behaviors. Lastly, there was evidence of significant relationships between the
      Care Plan Checklist for Evidence of Person-Centered Approaches for BPSD and the
      Cornell Scale for Depression in Dementia (r = 0.38, P < .001) and the Cohen
      Mansfield Agitation Inventory (r = 0.44, P < .001). There was not a significant
      relationship between resistiveness to care and scores on the Care Plan Checklist
      for Evidence of Person-Centered Approaches for BPSD (r = -0.02, P = .86). There
      were 78 care plans that were so low in evidence of using appropriate
      interventions that they could not be differentiated. CONCLUSIONS: There was
      sufficient evidence for the reliability and validity of the Care Plan Checklist
      for Evidence of Person-Centered Approaches for BPSD. Additional items should be
      considered to better differentiate those low on the Checklist for Evidence of
      Person-Centered Approaches for BPSD.

PMID- 29191764
TI  - Nursing Home-Hospice Collaboration and End-of-Life Hospitalizations Among Dying
      Nursing Home Residents.
AB  - OBJECTIVES: Nursing homes (NHs) collaboration with hospices appears to improve
      end-of-life (EOL) care among dying NH residents. However, the potential benefits
      of NH-hospice collaboration may vary with the patterns of this collaboration.
      This study examines the relationship between the attributes of NH-hospice
      collaboration, especially the exclusivity of NH-hospice collaboration (ie, the
      number of hospice providers in a NH), and EOL hospitalizations among dying NH
      residents. DESIGN: This national retrospective cohort study linked 2000-2009 NH
      assessments (ie, the Minimum Data Set 2.0) and Medicare data. A linear
      probability model with facility fixed-effects was estimated to examine the
      relationship between EOL hospitalization and the attributes of NH-hospice
      collaborations, adjusting for individual and facility characteristics. We also
      performed a set of sensitivity analyses, including stratified analyses by volume
      of hospice services in a NH and stratified analyses by rural vs urban NH
      locations. SETTINGS: All Medicare and/or Medicaid certified US NHs with at least
      8 years of data and at least 30 beds. PARTICIPANTS: NH decedents resided in
      Medicare and/or Medicaid certified NHs in the US between 2000 and 2009. We
      restricted the analyses to those continuously enrolled in Medicare fee-for
      service in the last 6 months of life and those who were in NHs for the last 30
      days of life. In total, we identified 2,954,276 NH decedents over the study
      period. MEASUREMENTS: The outcome variable was measured as dichotomous,
      indicating whether a dying NH resident was hospitalized in the last 30 days of
      life. The attributes of NH-hospice collaboration were measured by the volume of
      hospice services (defined as the ratio of number of hospice days to the total NH
      days per NH per calendar year) and the number of hospice providers in a NH
      (defined as the number of unique hospice providers in a NH per year). We
      categorized NHs into groups based on the number of hospice providers (1, 2 or 3,
      and >=4) in the NH, and conducted sensitivity analysis using a different
      categorization (1, 2, and 3+ hospice providers). RESULTS: The pattern of NH
      hospice collaboration changed significantly over years; the average number of
      hospices in a NH increased from 1.4 in 2000 to 3.2 in 2009. The volume of NH
      hospice collaboration also increased substantially. The multivariate regression
      analyses indicated that having more hospice providers in the NH was not
      associated with lower risks of EOL hospitalizations. After accounting for
      individual and facility characteristics, increasing hospice providers from 1 to
      at least 4 was associated with an overall 1 percentage point increase in the
      likelihood of EOL hospitalizations among dying residents (P < .01), and such
      relationship remained in NHs with moderate or high volume NHs in the stratified
      analyses. Stratified analysis by rural vs urban NHs suggested that the
      relationship between the number of hospice providers and EOL hospitalizations was
      mainly in urban NHs. CONCLUSIONS: More hospice providers in the NH was not
      associated with lower EOL hospitalizations, especially among NHs with relatively
      high volume of hospice services.

PMID- 29191765
TI  - Platypnea-Orthodeoxia Syndrome Masked by Delirium in an 85-Year-Old Woman.

PMID- 29191766
TI  - JAMDA's New Editors-in-Chief Present a Vision for the Journal of Post-Acute and
      Long-Term Care Medicine.

PMID- 29191767
TI  - Capsaicin, the primary constituent of pepper sprays and its pharmacological
      effects on mammalian ocular tissues.
AB  - Capsaicin is the principal constituent of oleoresin capsicum, or pepper spray, as
      it is commonly known. Pepper sprays are frequently used in riot control
      situations by defence organizations all over the world to deal with uncontrolled
      civil or criminal disturbances. Although capsaicin is noted for its irritant and
      inflammatory properties, the ocular profile of capsaicin has not been
      specifically studied and interpreted. The present review analyses the mammalian
      opthalmological profile of capsaicin and its pharmacological and toxicological
      manifestations including capsaicin induced corneal changes, neurogenic
      inflammation, neuroprotective influences on retinal ganglion cells (RGCs),
      depletion of neuropeptide content in sensory nerve terminals etc. Substantial
      views on the capsaicin receptor Transient Receptor Potential Vanilloid V1
      (TRPV1), its presence, significance and capsaicin induced mediations have been
      presented. Studies conducted previously on the reversal of capsaicin evoked
      ocular responses have been briefly demonstrated. In this regard, TRPV1
      antagonists (especially the competitive antagonist Capsazepine) have been
      indicated as potential candidates in mitigating or alleviating capsaicin elicited
      ocular responses. The review overall is a comprehensive perspective of the ocular
      inflammatory and pharmacological responses generated on exposure to capsaicin and
      concludes suggesting a possible regulatory framework for relief from the same
      presumably by the employment of specialized and target specific TRPV1
      antagonists.

PMID- 29191768
TI  - Interactions of aliskiren, a direct renin inhibitor, with antiepileptic drugs in
      the test of maximal electroshock in mice.
AB  - Experimental studies showed that certain angiotensin-converting enzyme inhibitors
      and angiotensin AT1 receptor antagonists can decrease seizure severity in
      rodents. Additionally, some of these blockers of the renin-angiotensin system
      have been documented to enhance the anticonvulsant activity of antiepileptic
      drugs against maximal electroshock-induced seizures. The aim of the current study
      was to investigate the effect of aliskiren, a direct renin inhibitor and a novel
      antihypertensive drug, on the protective action of numerous antiepileptic drugs
      (carbamazepine, valproate, clonazepam, phenobarbital, oxcarbazepine, lamotrigine,
      topiramate and pregabalin) in the test of maximal electroshock in mice. The
      examined drugs were administered intraperitoneally. Aliskiren up to a dose of
      75mg/kg did not affect the threshold for electroconvulsions, however, aliskiren
      (75mg/kg) enhanced the anticonvulsant action of clonazepam and valproate.
      Following aliskiren treatment, a higher brain concentration of valproate was
      noted, suggesting a pharmacokinetic interaction. In the rota-rod test, the
      concomitant treatment with aliskiren (50 or 75mg/kg) and clonazepam (22.6mg/kg)
      impaired motor coordination while clonazepam (22.6mg/kg) alone showed strong
      tendency towards this impairment. The combination of aliskiren (75mg/kg) with
      phenobarbital (25.5mg/kg) caused long-term memory deficits in the passive
      avoidance task. This study shows that there are no negative interactions between
      aliskiren and the examined antiepileptic drugs as concerns their anticonvulsant
      activity. Aliskiren even potentiated the anticonvulsant action of clonazepam and
      valproate against maximal electroshock. The impact of aliskiren alone on seizure
      activity or on the anticonvulsant and adverse activity of antiepileptic drugs
      needs further evaluation in other animal models of seizures.

PMID- 29191769
TI  - Berberine protects acute liver failure in mice through inhibiting inflammation
      and mitochondria-dependent apoptosis.
AB  - Acute liver failure (ALF) is characterized by sudden large area of inflammation
      and extensive hepatocyte apoptosis. This study identified the natural product
      berberine as a potential agent for acute liver failure(ALF). First, in vitro, BBR
      pre-incubation (5, 10 and 20MUM) alleviated L02 hepatocytes injury induced by D
      GalN (5mM)/TNF-alpha (100ng/ml). Second, in vivo, BBR pre-treatment attenuated D
      Galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver failure, as
      evidenced by the reduction of mortality, the alleviation of liver pathological
      changes and the inhibition of alanine aminotransferase (ALT)/aspartate
      aminotransferase (AST). Our results further illustrated that BBR inhibited the
      nuclear translocation of NF-kappaB p65 and subsequently suppressed the
      expressions of inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6) at both mRNA and protein levels in ALF. Moreover,
      western blotting demonstrated that BBR effectively inhibited apoptosis via
      reducing cytochrome c release, Bax/Bcl-2 ratio and caspase-3/-9 cleavage in vitro
      and in vivo. In conclusion, our findings suggest that BBR serves as a potential
      agent for preventing or treating human ALF by inhibiting inflammation and
      mitochondria-dependent apoptosis.

PMID- 29191770
TI  - Auditory-motor coupling affects phonetic encoding.
AB  - Recent studies have shown that moving in synchrony with auditory stimuli boosts
      attention allocation and verbal learning. Furthermore rhythmic tones are
      processed more efficiently than temporally random tones ('timing effect'), and
      this effect is increased when participants actively synchronize their motor
      performance with the rhythm of the tones, resulting in auditory-motor
      synchronization. Here, we investigated whether this applies also to sequences of
      linguistic stimuli (syllables). We compared temporally irregular syllable
      sequences with two temporally regular conditions where either the interval
      between syllable onsets (stimulus onset asynchrony, SOA) or the interval between
      the syllables' vowel onsets was kept constant. Entrainment to the stimulus
      presentation frequency (1 Hz) and event-related potentials were assessed in 24
      adults who were instructed to detect pre-defined deviant syllables while they
      either pedaled or sat still on a stationary exercise bike. We found larger 1 Hz
      entrainment and P300 amplitudes for the SOA presentation during motor activity.
      Furthermore, the magnitude of the P300 component correlated with the motor
      variability in the SOA condition and 1 Hz entrainment, while in turn 1 Hz
      entrainment correlated with auditory-motor synchronization performance. These
      findings demonstrate that acute auditory-motor coupling facilitates phonetic
      encoding.

PMID- 29191771
TI  - Silencing rno-miR-155-5p in rat temporal lobe epilepsy model reduces
      pathophysiological features and cell apoptosis by activating Sestrin-3.
AB  - Temporal lobe epilepsy (TLE) is a chronic neurological disease characterized by
      recurrent spontaneous seizures. MicroRNAs are dysregulated in various
      pathological conditions including epilepsy. Therefore, we hypothesized that the
      dysregulation of these microRNAs might also be associated with the pathogenesis
      of TLE. In this study, we found that a microRNA, hsa-miR-155-5p, was upregulated
      in patients with TLE post-surgery, and hence associated with clinical and
      pathological manifestations and seizure outcomes. We then used a rat model of
      experimental epilepsy induced by pilocarpine and revealed that the rat homologue
      was upregulated as well. Importantly, injection of an antagomiR of rno-miR-155-5p
      in vivo resulted in a reduction of the pathophysiological features associated
      with the status epilepticus, which was accompanied by decrease of apoptosis in
      the hippocampus. This effect was correlated with an increase in rat Sestrin-3
      expression, which was a gene known to counteract oxidative stress. This rescue
      was also observed after injection of a lentivirus carrying the small interfering
      RNA of rat Sestrin-3 gene in the hippocampus. In addition, rno-miR-155-5p as well
      as rat Sestrin-3 mRNA and protein expression were partly dependent on oxidative
      stress induced by H2O2 in PC12 cells. Taken together, our data suggest that rno
      miR-155-5p is a potent post-transcriptional regulator of rat Sestrin-3 and it may
      be one of the molecular links between brain damage and increased risk for
      seizures during damage by oxidative stress.

PMID- 29191772
TI  - Gap-induced reductions of evoked potentials in the auditory cortex: A possible
      objective marker for the presence of tinnitus in animals.
AB  - Animal models of tinnitus are essential for determining the underlying mechanisms
      and testing pharmacotherapies. However, there is doubt over the validity of
      current behavioural methods for detecting tinnitus. Here, we applied a stimulus
      paradigm widely used in a behavioural test (gap-induced inhibition of the
      acoustic startle reflex GPIAS) whilst recording from the auditory cortex, and
      showed neural response changes that mirror those found in the behavioural tests.
      We implanted guinea pigs (GPs) with electrocorticographic (ECoG) arrays and
      recorded baseline auditory cortical responses to a startling stimulus. When a gap
      was inserted in otherwise continuous background noise prior to the startling
      stimulus, there was a clear reduction in the subsequent evoked response (termed
      gap-induced reductions in evoked potentials; GIREP), suggestive of a neural
      analogue of the GPIAS test. We then unilaterally exposed guinea pigs to
      narrowband noise (left ear; 8-10 kHz; 1 h) at one of two different sound levels -
      either 105 dB SPL or 120 dB SPL - and recorded the same responses seven-to-ten
      weeks following the noise exposure. Significant deficits in GIREP were observed
      for all areas of the auditory cortex (AC) in the 120 dB-exposed GPs, but not in
      the 105 dB-exposed GPs. These deficits could not simply be accounted for by
      changes in response amplitudes. Furthermore, in the contralateral (right) caudal
      AC we observed a significant increase in evoked potential amplitudes across
      narrowband background frequencies in both 105 dB and 120 dB-exposed GPs. Taken in
      the context of the large body of literature that has used the behavioural test as
      a demonstration of the presence of tinnitus, these results are suggestive of
      objective neural correlates of the presence of noise-induced tinnitus and
      hyperacusis.

PMID- 29191774
TI  - Endogenous Pain Modulation Induced by Extrinsic and Intrinsic Psychological
      Threat in Healthy Individuals.
AB  - : Many factors interact to influence threat perception and the subsequent
      experience of pain. This study investigated the effect of observing pain
      (extrinsic threat) and intrinsic threat of pain to oneself on pressure pain
      threshold (PPT). Forty socially connected pairs of healthy volunteers were threat
      primed and randomly allocated to experimental or control roles. An experimental
      pain modulation paradigm was applied, with non-nociceptive threat cues used as
      conditioning stimuli. In substudy 1, the extrinsic threat to the experimental
      participant was observation of the control partner in pain. The control
      participant underwent hand immersion in noxious and non-noxious water baths in
      randomized order. Change in the observing participant's PPT from baseline to mid-
      and postimmersion was calculated. A significant interaction was found for PPT
      between conditions and test time (F2,78 = 24.9, P < .005). PPT increased by 23.6%
      +/- 19.3% between baseline and during hand immersion (F1,39 = 43.7, P < .005).
      Substudy 2 investigated threat of imminent pain to self. After a 15-minute break,
      the experimental participant's PPT was retested ("baseline 2"). Threat was primed
      by suggestion of whole arm immersion in an icier, larger water bath. PPT was
      tested immediately before anticipated arm immersion, after which the experiment
      ended. A significant increase in PPT between "baseline 2" and "pre-immersion" was
      seen (t = -7.6, P = .005), a pain modulatory effect of 25.8 +/- 20.7%. Extrinsic
      and intrinsic threat of pain, in the absence of any afferent input therefore
      influences pain modulation. This may need to be considered in studies that use
      noxious afferent input with populations who show dysfunctional pain modulation.
      PERSPECTIVE: The effect on endogenous analgesia of observing another's pain and
      of threat of pain to oneself was investigated. Extrinsic as well as intrinsic
      threat cues, in the absence of any afferent input, increased pain thresholds,
      suggesting that mere threat of pain may initiate analgesic effects in traditional
      noxious experimental paradigms.

PMID- 29191775
TI  - Agreement of different reference equations to classify patients with COPD as
      having reduced or preserved 6MWD.
AB  - BACKGROUND: Interpretation of the six-minute walk distance (6MWD) is enhanced by
      using recommended reference equations. Whenever possible, the choice of equation
      should be region-specific. A potential problem is that different equations for
      the 6MWD may have been developed for the same population, and it may be
      complicated to choose the most suitable. OBJECTIVE: To verify the agreement of
      different reference equations in classifying patients with Chronic Obstructive
      Pulmonary Disease (COPD) as having reduced or preserved 6MWD. METHODS: 159
      patients with COPD performed the six-minute walk test according to international
      standardization. They were classified as having reduced 6MWD if it was below the
      lower limit of normal. Five Brazilian equations (Iwama; Britto1; Britto2;
      Dourado; Soares) and the two non-Brazilian equations most cited worldwide
      (Troosters; Enright) were used. The agreement for patients classified as reduced
      or preserved 6MWD was verified by Cohen's Kappa (pair-to-pair) analysis. The
      proportion of patients classified as having reduced walked distance was compared
      by the Chi-squared test. RESULTS: Agreement between equations varied largely in
      classifying subjects as having reduced or preserved 6MWD (Kappa: 0.10-0.82).
      Brazilian equations with the highest agreement were Iwama, Britto1 and Britto2
      (Kappa>0.75). The proportion of patients classified as having reduced 6MWD was
      statistically similar only between equations in which the agreement was higher
      than 0.70. CONCLUSION: Even reference equations from the same country vary
      considerably in the classification of reduced or preserved 6MWD, and it is
      recommended that the region-specific ones be used as they give with higher
      agreement for similar and comparable interpretation of the patients' functional
      exercise capacity.

PMID- 29191773
TI  - Expression of channelrhodopsin-2 localized within the deep CA1 hippocampal
      sublayer in the Thy1 line 18 mouse.
AB  - Optogenetic proteins are powerful tools for advancing our understanding of neural
      circuitry. However, the precision of optogenetics is dependent in part on the
      extent to which expression is limited to cells of interest. The Thy1-ChR2
      transgenic mouse is commonly used in optogenetic experiments. Although general
      expression patterns in these animals have been characterized, a detailed
      evaluation of cell-type specificity is lacking. This information is critical for
      interpretation of experimental results using these animals. We characterized ChR2
      expression under the Thy1promoter in line 18 in comparison to known expression
      profiles of hippocampal cell types using immunohistochemistry in CA1. ChR2
      expression did not colocalize with parvalbumin or calbindin expressing
      interneurons. However, we found ChR2 expression to be localized in the deep
      sublayer of CA1 in calbindin-negative pyramidal cells. These findings demonstrate
      the utility of the Thy1-ChR2-YFP mouse to study the activity and functional role
      of excitatory neurons located in the deep CA1 pyramidal cell layer.

PMID- 29191777
TI  - Clinical Significance of Plasma Epstein-Barr Virus DNA in Pulmonary
      Lymphoepithelioma-like Carcinoma (LELC) Patients.
AB  - INTRODUCTION: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a
      histologically distinctive subtype of NSCLC and an Epstein-Barr virus (EBV)
      associated epithelial neoplasm. We investigated the clinical significance of
      plasma concentrations of EBV DNA in patients with pulmonary LELC. METHODS: Two
      independent sets of plasma samples from a total of 429 patients with patients
      with pulmonary LELC (287 initial and 142 confirmatory) were available for EBV DNA
      determination. Plasma samples from the patients were subjected to a real-time
      quantitative polymerase chain reaction before treatment and 3 months after
      radical resection. Cutoff points were determined for pretreatment plasma EBV DNA
      concentration (low <4000 copies/mL versus high >=4000 copies/mL) on the basis of
      a measure of heterogeneity with the log-rank test statistic with respect to
      overall survival (OS). The Kaplan-Meier method and Cox regression were used to
      evaluate the relationship between plasma EBV DNA concentrations and clinical
      outcome. Among patients with advanced-stage pulmonary LELC who underwent
      sequential blood draws, we evaluated the relationship between change in disease
      status and change in EBV DNA concentrations by using nonparametric tests.
      RESULTS: High EBV DNA concentration was associated with shorter OS in the
      initial, confirmatory, and combined data sets (combined data set hazard ratio =
      3.67, 95% confidence interval: 2.72-4.38, p < 0.001). These findings persisted
      after multivariable adjustment. Compared with low EBV DNA concentration, high EBV
      DNA concentration was associated with shorter OS in patients with any stage of
      disease. High EBV DNA concentration was also associated with shorter disease-free
      survival (DFS) in patients with stage I/II disease. Patients with persistently
      detectable plasma EBV DNA had significantly poorer OS (p < 0.001) and DFS (p <
      0.001) than did patients with undetectable EBV DNA 3 months after radical
      resection. In patients who underwent sequential evaluation of EBV DNA, an
      association was identified between an increase in EBV DNA concentration and a
      poor response to treatment and disease progression of pulmonary LELC. CONCLUSION:
      High baseline EBV DNA concentration is an independent poor prognostic marker in
      patients with pulmonary LELC. These results should be confirmed in larger
      prospective trials.

PMID- 29191778
TI  - Paraneoplastic Syndromes and Thymic Malignancies: An Examination of the
      International Thymic Malignancy Interest Group Retrospective Database.
AB  - INTRODUCTION: Thymic epithelial tumors (TETs) are associated with
      paraneoplastic/autoimmune (PN/AI) syndromes. Myasthenia gravis is the most common
      PN/AI syndrome associated with TETs. METHODS: The International Thymic Malignancy
      Interest Group retrospective database was examined to determine (1) baseline and
      treatment characteristics associated with PN/AI syndromes and (2) the prognostic
      role of PN/AI syndromes for patients with TETs. The competing risks model was
      used to estimate cumulative incidence of recurrence (CIR) and the Kaplan-Meier
      method was used to calculate overall survival (OS). A Cox proportional hazards
      model was used for multivariate analysis. RESULTS: A total of 6670 patients with
      known PN/AI syndrome status from 1951 to 2012 were identified. PN/AI syndromes
      were associated with younger age, female sex, thymoma histologic type, earlier
      stage, and an increased rate of total thymectomy and complete resection status.
      There was a statistically significant lower CIR in the group with a PN/AI
      syndrome than in the group without a PN/AI syndrome (10-year CIR 17.3% versus
      21.2%, respectively [p = 0.0003]). The OS was improved in the group with a PN/AI
      syndrome compared to the group without a PN/AI syndrome (median OS 21.6 years
      versus 17.0 years, respectively [hazard ratio = 0.63, 95% confidence interval:
      0.54-0.74, p < 0.0001]). However, in the multivariate model for recurrence-free
      survival and OS, PN/AI syndrome was not an independent prognostic factor.
      DISCUSSION: Previously, there have been mixed data regarding the prognostic role
      of PN/AI syndromes for patients with TETs. Here, using the largest data set in
      the world for TETs, PN/AI syndromes were associated with favorable features
      (i.e., earlier stage and complete resection status) but were not an independent
      prognostic factor for patients with TETs.

PMID- 29191779
TI  - Fusion Imaging for Procedural Guidance.
AB  - The field of percutaneous structural heart interventions has grown tremendously
      in recent years. This growth has fueled the development of new imaging protocols
      and technologies in parallel to help facilitate these minimally-invasive
      procedures. Fusion imaging is an exciting new technology that combines the
      strength of 2 imaging modalities and has the potential to improve procedural
      planning and the safety of many commonly performed transcatheter procedures. In
      this review we discuss the basic concepts of fusion imaging along with the
      relative strengths and weaknesses of static vs dynamic fusion imaging modalities.
      This review will focus primarily on echocardiographic-fluoroscopic fusion imaging
      and its application in commonly performed transcatheter structural heart
      procedures.

PMID- 29191776
TI  - Evaluation of NGS and RT-PCR Methods for ALK Rearrangement in European NSCLC
      Patients: Results from the European Thoracic Oncology Platform Lungscape Project.
AB  - INTRODUCTION: The reported prevalence of ALK receptor tyrosine kinase gene (ALK)
      rearrangement in NSCLC ranges from 2% to 7%. The primary standard diagnostic
      method is fluorescence in situ hybridization (FISH). Recently,
      immunohistochemistry (IHC) has also proved to be a reproducible and sensitive
      technique. Reverse-transcriptase polymerase chain reaction (RT-PCR) has also been
      advocated, and most recently, the advent of targeted next-generation sequencing
      (NGS) for ALK and other fusions has become possible. This study compares
      anaplastic lymphoma kinase (ALK) evaluation with all four techniques in resected
      NSCLC from the large European Thoracic Oncology Platform Lungscape cohort.
      METHODS: A total of 96 cases from the European Thoracic Oncology Platform
      Lungscape iBiobank, with any ALK immunoreactivity were examined by FISH, central
      RT-PCR, and NGS. An H-score higher than 120 defines IHC positivity. RNA was
      extracted from the same formalin-fixed, paraffin-embedded tissues. For RT-PCR,
      primers covered the most frequent ALK translocations. For NGS, the Oncomine Solid
      Tumour Fusion Transcript Kit (Thermo Fisher Scientific, Waltham, MA) was used.
      The concordance was assessed using the Cohen kappa coefficient (two-sided alpha
      <= 5%). RESULTS: NGS provided results for 77 of the 95 cases tested (81.1%),
      whereas RT-PCR provided results for 77 of 96 (80.2%). Concordance occurred in 55
      cases of the 60 cases tested with all four methods (43 ALK negative and 12 ALK
      positive). Using ALK copositivity for IHC and FISH as the criterion standard, we
      derived a sensitivity for RT-PCR/NGS of 70.0%/85.0%, with a specificity of
      87.1%/79.0%. When either RT-PCR or NGS was combined with IHC, the sensitivity
      remained the same, whereas the specificity increased to 88.7% and 83.9%
      respectively. CONCLUSION: NGS evaluation with the Oncomine Solid Tumour Fusion
      transcript kit and RT-PCR proved to have high sensitivity and specificity,
      advocating their use in routine practice. For maximal sensitivity and
      specificity, ALK status should be assessed by using two techniques and a third
      one in discordant cases. We therefore propose a customizable testing algorithm.
      These findings significantly influence existing testing paradigms and have clear
      clinical and economic impact.

PMID- 29191780
TI  - The Value of the SYNTAX Score II in Predicting Clinical Outcomes in Patients
      Undergoing Transcatheter Aortic Valve Implantation.
AB  - INTRODUCTION AND OBJECTIVES: The predictive value of the SYNTAX score (SS) for
      clinical outcomes after transcatheter aortic valve implantation (TAVI) is very
      limited and could potentially be improved by the combination of anatomic and
      clinical variables, the SS-II. We aimed to evaluate the value of the SS-II in
      predicting outcomes in patients undergoing TAVI. METHODS: A total of 402 patients
      with severe symptomatic aortic stenosis undergoing transfemoral TAVI were
      included. Preprocedural TAVI angiograms were reviewed and the SS-I and SS-II were
      calculated using the SS algorithms. Patients were stratified in 3 groups
      according to SS-II tertiles. The coprimary endpoints were all-cause death and
      major adverse cardiovascular events (MACE), a composite of all-cause death,
      cerebrovascular event, or myocardial infarction at 1 year. RESULTS: Increased SS
      II was associated with higher 30-day mortality (P=.036) and major bleeding
      (P=.015). The 1-year risk of death and MACE was higher among patients in the 3rd
      SS-II tertile (HR, 2.60; P=.002 and HR, 2.66; P<.001) and was similar among
      patients in the 2nd tertile (HR, 1.27; P=.507 and HR, 1.05; P=.895) compared with
      patients in the 1st tertile. The highest SS-II tertile was an independent
      predictor of long-term mortality (P=.046) and MACE (P=.001). CONCLUSIONS: The SS
      II seems more suited to predict clinical outcomes in patients undergoing TAVI
      than the SS-I. Increased SS-II was associated with poorer clinical outcomes at 1
      and 4 years post-TAVI, independently of the presence of coronary artery disease.

PMID- 29191781
TI  - Analysis of Hospitalization Trends for Heart Failure in the Health Registries of
      Different Autonomous Communities.

PMID- 29191783
TI  - Executive-related oculomotor control is improved following a 10-min single-bout
      of aerobic exercise: Evidence from the antisaccade task.
AB  - Previous work has shown that a single-bout of moderate-to-vigorous intensity
      exercise improves task-specific activity within frontoparietal networks and
      produces a short-term 'boost' to executive-related cognitive control - an effect
      in healthy young adults that is reported to be selective to exercise durations of
      20min or greater. The present study sought to determine whether such a 'boost'
      extends to an exercise duration as brief as 10min. Healthy young adults performed
      a 10-min single-bout of moderate-to-vigorous intensity aerobic exercise (i.e.,
      via a cycle ergometer) and pre- and post-exercise executive control was examined
      via the antisaccade task. Antisaccades are an executive task requiring a goal
      directed eye movement (i.e., a saccade) mirror-symmetrical to a visual stimulus.
      The hands- and language-free nature of antisaccades coupled with the temporal
      precision of eye-tracking technology make it an ideal tool for identifying
      executive performance changes. Moreover, an extensive literature has shown that
      antisaccades are mediated via frontoparietal networks that are modulated
      following single-bout and chronic exercise training. Results showed that
      antisaccade reaction time (RT) reliably decreased by 27ms from pre- to post
      exercise assessments. Further, the percentage of antisaccade directional errors
      did not reliably vary from the pre- (13%) to post-exercise (9%) assessments - a
      result indicating that the RT improvement was unrelated to a speed-accuracy trade
      off. A follow-up experiment involving antisaccade sessions separated by a non
      exercise interval did not show a similar RT modulation. Thus, a 10-min bout of
      moderate-to-vigorous intensity aerobic exercise benefits executive-related
      oculomotor control, and is a finding we attribute to an exercise-based increase
      in attention/arousal and/or improved task-specific activity within the
      frontoparietal networks supporting antisaccades.

PMID- 29191782
TI  - Comparison of the Hemodynamic Performance of the Balloon-expandable SAPIEN 3
      Versus Self-expandable Evolut R Transcatheter Valve: A Case-matched Study.
AB  - INTRODUCTION AND OBJECTIVES: The SAPIEN 3 (S3) valve and the Medtronic Evolut R
      (EVR) are second-generation transcatheter valves, designed to further reduce the
      rate of paravalvular aortic regurgitation (AoR). The aim of this study was to
      compare the 2 devices in terms of valve performance in a case-matched study with
      independent echocardiographic analysis. METHODS: Of a population of 201 patients
      who underwent transcatheter aortic valve implantation, 144 patients (S3, n = 80;
      EVR, n = 64) were matched according to aortic annulus diameter and aortic valve
      calcium score, as assessed by computed tomography. All echocardiographic
      examinations collected at baseline and at 1- and 6-month follow-up were centrally
      analyzed. RESULTS: The 2 groups were well balanced in baseline clinical and
      echocardiographic characteristics. The EVR valve showed a better hemodynamic
      profile as assessed by peak aortic gradient (EVR 13 +/- 7 vs S3 20 +/- 10mmHg;
      P<.001), mean aortic gradient (EVR 7 +/- 3 vs S3 11 +/- 6mmHg; P<.001), and
      Doppler velocity index (EVR 0.65+/-0.15 vs S3 0.51+/-0.16; P<.001). The rate of
      moderate-severe or any paravalvular (>= mild) AoR was higher in the EVR group
      (11% and 50%) than in the S3 group (2.5% and 21%; P <.05, respectively), with a
      larger number of paravalvular jets (P <.001). CONCLUSIONS: In a case-matched
      cohort of transcatheter aortic valve implantation patients, the S3 valve was
      associated with a lower rate of paravalvular AoR but also with a higher residual
      gradient than the EVR system.

PMID- 29191784
TI  - Nanoparticulate peptide delivery exclusively to the brain produces tolerance free
      analgesia.
AB  - The delivery of peptide drugs to the brain is challenging, principally due to the
      blood brain barrier and the low metabolic stability of peptides. Exclusive
      delivery to the brain with no peripheral exposure has hitherto not been
      demonstrated with brain quantification data. Here we show that polymer
      nanoparticles encapsulating leucine5-enkephalin hydrochloride (LENK) are able to
      transport LENK exclusively to the brain via the intranasal route, with no
      peripheral exposure and nanoparticle localisation is observed within the brain
      parenchyma. Animals dosed with LENK nanoparticles (NM0127) showed a strong anti
      nociceptive response in multiple assays of evoked and on going pain whereas
      animals dosed intranasally with LENK alone were unresponsive. Animals did not
      develop tolerance to the anti-hyperalgesic activity of NM0127 and NM0127 was
      active in morphine tolerant animals. A microparticulate formulation of clustered
      nanoparticles was prepared to satisfy regulatory requirements for nasal dosage
      forms and the polymer nanoparticles alone were found to be biocompatible, via the
      nasal route, on chronic dosing.

PMID- 29191785
TI  - Folate-targeted liposomal nitrooxy-doxorubicin: An effective tool against P
      glycoprotein-positive and folate receptor-positive tumors.
AB  - Drug efflux transporters, in particular P-glycoprotein (Pgp), limit the success
      of chemotherapy. We previously found that synthetic doxorubicin conjugated with
      nitric oxide (NO)-releasing group overcomes resistance by inducing a NO-mediated
      inhibition of Pgp. Here we produced the first liposomal formulations of this
      nitrooxy-doxorubicin decorated with folic acid (FA), termed LNDF, in order to
      improve their active targeting against Pgp-expressing tumors. Folate was inserted
      onto liposomes surface using two different methods and the formulations were
      compared with respect to their technological features and in vitro behavior. By
      analyzing human and murine breast cancer cells with different expression of FA
      receptor (FAR) and Pgp, we demonstrated that LNDF are internalized in a FAR
      dependent manner and achieve maximal anti-tumor efficacy against FAR-positive/Pgp
      positive cells. Upon uptake of LNDF, nitrooxy-doxorubicin was delivered within
      nucleus, where it induced cell cycle arrest and DNA damages, and mitochondria,
      where it impaired the mitochondrial energy metabolism and triggered mitochondria
      dependent apoptosis. LNDF reduced the growth of FAR-positive/Pgp-positive tumors
      and prevented tumor formation in mice, whereas doxorubicin and Caelyx(r) failed.
      LNDF cardiotoxicity was comparable to Caelyx(r). The sensitivity to LNDF was
      maintained in tumors exposed to repeated cycles of the drug and in cells derived
      from the exposed tumors, excluding the onset of secondary resistance. By
      combining an innovative multitarget cargo drug, conceived to achieve high
      efficacy against Pgp-expressing cells, and appropriate strategies of liposome
      formulation and decoration, we produced a therapeutic tool that may represent a
      significant advancement in the treatment of FAR-positive/Pgp-positive tumors.

PMID- 29191786
TI  - KIR-HLA distribution in a Vietnamese population from Hanoi.
AB  - The KIR (killer cell immunoglobulin-like receptors) gene family codifies a group
      of receptors that recognize human leukocyte antigens (HLA) and modulate natural
      killer (NK) cells response. Genetic diversity of KIR genes and HLA ligands has
      not yet been deeply investigated in South East Asia. Here, we characterized KIR
      gene presence and absence polymorphism of 14 KIR genes and two pseudogenes, as
      well as the frequencies of the ligands HLA-Bw4, HLA-C1 and HLA-C2 in a Vietnamese
      population from Hanoi (n = 140). Genotyping was performed by polymerase chain
      reaction with specific sequence primers (PCR-SSP). We compared KIR frequencies
      and performed principal component analysis with 43 worldwide populations of
      different ancestries. KIR carrier frequencies in Vietnamese were similar to those
      reported for Thai and Chinese Han, but differed significantly from other
      geographically close populations such as Japanese and South Korean. This
      similarity was also observed in KIR gene-content genotypes and is in accordance
      with the origin from Southern China and Thailand proposed for the Vietnamese
      population. The frequencies of HLA ligands observed in Vietnamese did not differ
      from those reported for other East-Asian populations (p > .05). Studies regarding
      KIR-HLA in populations are of prime importance to understand their evolution,
      function and role in diseases.

PMID- 29191787
TI  - Post-translational regulation of metabolism in fumarate hydratase deficient
      cancer cells.
AB  - Deregulated signal transduction and energy metabolism are hallmarks of cancer and
      both play a fundamental role in tumorigenesis. While it is increasingly
      recognised that signalling and metabolism are highly interconnected, the
      underpinning mechanisms of their co-regulation are still largely unknown. Here we
      designed and acquired proteomics, phosphoproteomics, and metabolomics experiments
      in fumarate hydratase (FH) deficient cells and developed a computational
      modelling approach to identify putative regulatory phosphorylation-sites of
      metabolic enzymes. We identified previously reported functionally relevant
      phosphosites and potentially novel regulatory residues in enzymes of the central
      carbon metabolism. In particular, we showed that pyruvate dehydrogenase (PDHA1)
      enzymatic activity is inhibited by increased phosphorylation in FH-deficient
      cells, restricting carbon entry from glucose to the tricarboxylic acid cycle.
      Moreover, we confirmed PDHA1 phosphorylation in human FH-deficient tumours. Our
      work provides a novel approach to investigate how post-translational
      modifications of enzymes regulate metabolism and could have important
      implications for understanding the metabolic transformation of FH-deficient
      cancers with potential clinical applications.

PMID- 29191788
TI  - Progressive impairment of atrial myocyte function during left ventricular
      hypertrophy and heart failure.
AB  - Hypertensive heart disease (HHD) can cause left ventricular (LV) hypertrophy and
      heart failure (HF). It is unclear, though, which factors may contribute to the
      transition from compensated LV hypertrophy to HF in HHD. We hypothesized that
      maladaptive atrial remodeling with impaired atrial myocyte function would occur
      in advanced HHD and may be associated with the emergence of HF. Experiments were
      performed on atrial myocytes and tissue from old (15-25months) normotensive
      Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with advanced
      HHD. Based on the absence or presence of elevated lung weight, a sign of lung
      congestion and heart failure, SHR were divided into a non-failing (SHR-NF) and
      failing (SHR-HF) group. Compared with WKY, SHR exhibited elevated blood pressure,
      LV hypertrophy and left atrial (LA) hypertrophy with increased LA expression of
      markers of hypertrophy and fibrosis. SHR-HF were distinguished from SHR-NF by
      aggravated hypertrophy and fibrosis. SHR-HF atrial myocytes exhibited reduced
      contractility and impaired SR Ca2+ handling. Moreover, in SHR the expression and
      phosphorylation of SR Ca2+-regulating proteins (SERCA2a, calsequestrin, RyR2 and
      phospholamban) showed negative correlation with increasing lung weight.
      Increasing stimulation frequency (1-2-4Hz) of atrial myocytes caused a
      progressive increase in arrhythmogenic Ca2+ release (including alternans), which
      was observed most frequently in SHR-HF. Thus, in old SHR with advanced HHD there
      is profound structural and functional atrial remodeling. The occurrence of HF in
      SHR is associated with LA and RA hypertrophy, increased atrial fibrosis, impaired
      atrial myocyte contractility and SR Ca2+ handling and increased propensity for
      arrhythmogenic Ca2+ release. Therefore, functional remodeling intrinsic to atrial
      myocytes may contribute to the transition from compensated LV hypertrophy to HF
      in advanced HHD and an increased propensity of atrial arrhythmias in HF.

PMID- 29191789
TI  - Accidental sulfur mustard exposure: A case report.
AB  - The clinical progression following a sulfur mustard-induced skin exposure is well
      documented in the literature. Upon skin contact and a characteristic latency
      period, sulfur mustard (SM) causes erythema, blister formation and ulceration,
      which is associated with wound healing disorders that may require surgical
      treatment. Here, we present a case report of accidental exposure to SM in a
      laboratory setting which required surgical treatment of the skin. The case was
      illustrated at close intervals over a period of two years and underlines that
      exposure to SM has to be taken into account when typical clinical symptoms occur.
      Moreover skin grafts appear to be effective in SM-induced non healing skin
      ulcerations.

PMID- 29191790
TI  - Morphological and transcriptomic effects of endocrine modulators on the gonadal
      differentiation of chicken embryos: The case of tributyltin (TBT).
AB  - Morphological malformations induced by tributyltin (TBT) exposure during
      embryonic development have already been characterized in various taxonomic
      groups, but, nonetheless, the molecular processes underlying these changes remain
      obscure. The present study provides the first genome-wide screening for
      differentially expressed genes that are linked to morphological alterations of
      gonadal tissue from chicken embryos after exposure to TBT. We applied a single
      injection of TBT (between 0.5 and 30 pg as Sn/g egg) into incubated fertile eggs
      to simulate maternal transfer of the endocrine disruptive compound.
      Methyltestosterone (MT) served as a positive control (30 pg/g egg). After 19 days
      of incubation, structural features of the gonads as well as genome-wide gene
      expression profiles were assessed simultaneously. TBT induced significant
      morphological and histological malformations of gonadal tissue from female
      embryos that show a virilization of the ovaries. This phenotypical virilization
      was mirrored by altered expression profiles of sex-dependent genes. Among these
      are several transcription and growth factors (e.g. FGF12, CTCF, NFIB), whose
      altered expression might serve as a set of markers for early identification of
      endocrine active chemicals that affect embryonic development by transcriptome
      profiling without the need of elaborate histological analyses.

PMID- 29191791
TI  - Electrophysiological investigation of the effect of structurally different
      bispyridinium non-oxime compounds on human alpha7-nicotinic acetylcholine
      receptor activity-An in vitro structure-activity analysis.
AB  - Organophosphorus compounds, including nerve agents and pesticides, exert their
      toxicity through irreversible inhibition of acetylcholinesterase (AChE) resulting
      in an accumulation of acetylcholine and functional impairment of muscarinic and
      nicotinic acetylcholine receptors. Current therapy comprises oximes to reactivate
      AChE and atropine to antagonize effects induced by muscarinic acetylcholine
      receptors. Nicotinic malfunction leading to depression of the central and
      peripheral respiratory system is not directly treated calling for alternative
      therapeutic interventions. In the present study, we investigated the
      electrophysiological properties of the human nAChR subtype alpha7 (halpha7-nAChR)
      and the functional effect of the 4-tert-butyl bispyridinium (BP) compound MB327
      and of a series of novel substituted bispyridinium compounds on the receptors by
      an automated patch clamp technique. Activation of halpha7-nAChRs was induced by
      nicotine and acetylcholine demonstrating rapid cationic influx up to 100MUM.
      Agonist-induced currents decayed within a few milliseconds revealing fast
      desensitization of the receptors. Application of higher agonist concentrations
      led to a decline of current amplitudes which seemed to be due to increasing
      receptor desensitization. When 100MUM of agonist was coapplied with low
      concentrations of the well characterized alpha7-specific positive allosteric
      modulator PNU-120596 (1MUM-10MUM), the maximum response and duration of nAChR
      activation were markedly augmented indicating an elongated mean open-time of
      receptors and prevention of receptor desensitization. However, co-application of
      increasing PNU-120596 concentrations (>10MUM) with agonist induced a decline of
      potentiated current responses. Although less pronounced than PNU-120596, six of
      the twenty tested substituted BP compounds, in particular those with a
      substituent at 3-position and 4-position at the pyridinium moieties, were found
      to potentiate current responses of halpha7-nAChRs, most pronounced MB327.This
      effect was clearly depended on the presence of the agonist indicating a positive
      allosteric mechanism of these compounds. Besides potentiation at low
      concentrations, these compounds seem to interact at different binding sites on
      halpha7-nAChRs since enhancement decreased at high concentrations. The residual
      fourteen BP compounds, possessing either an isopropyl-group or more than one
      group at the pyridinium moiety, antagonized nicotinic currents exhibiting IC50 of
      low up to high micromolar concentrations (~1MUM-300MUM).

PMID- 29191792
TI  - The binding efficiency of RPA to telomeric G-strands folded into contiguous G
      quadruplexes is independent of the number of G4 units.
AB  - Replication protein A (RPA) is a single-stranded DNA binding protein involved in
      replication and in telomere maintenance. During telomere replication, G
      quadruplexes (G4) can accumulate on the lagging strand template and need to be
      resolved. It has been shown that human RPA is able to unfold a single G4.
      Nevertheless, the G-strand of human telomeres is prone to fold into higher-order
      structures formed by contiguous G-quadruplexes. To understand how RPA deals with
      these structures, we studied its interaction with telomeric G-strands folding
      into an increasing number of contiguous G4s. The aim of this study was to
      determine whether the efficiency of binding/unfolding of hRPA to telomeric G
      strands depends on the number of G4 units. Our data show that the number n of
      contiguous G4 units (n >= 2) does not affect the efficiency of hRPA to coat
      transiently exposed single-stranded telomeric G-strands. This feature may be
      essential in preventing instability due to G4 structures during telomere
      replication.

PMID- 29191793
TI  - Combined therapies to treat complex diseases: The role of the gut microbiota in
      multiple sclerosis.
AB  - The commensal microbiota has emerged as an environmental risk factor for multiple
      sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models
      have shown that the commensal microbiota is an essential player in triggering
      autoimmune demyelination. Likewise, the commensal microbiota modulates the host
      immune system, alters the integrity and function of biological barriers and has a
      direct effect on several types of central nervous system (CNS)-resident cells.
      Moreover, a characteristic gut dysbiosis has been recognized as a consistent
      feature during the clinical course of MS, and the MS-related microbiota is
      gradually being elucidated. This review highlights animal studies in which
      commensal microbiota modulation was tested in EAE, as well as the mechanisms of
      action and influence of the commensal microbiota not only in the local milieu but
      also in the innate and adaptive immune system and the CNS. Regarding human
      research, this review focuses on studies that show how the commensal microbiota
      might act as a pathogenic environmental risk factor by directing immune responses
      towards characteristic pathogenic profiles of MS. We speculate how specific
      microbiome signatures could be obtained and used as potential pathogenic events
      and biomarkers for the clinical course of MS. Finally, we review recently
      published and ongoing clinical trials in MS patients regarding the
      immunomodulatory properties exerted by some microorganisms. Because MS is a
      complex disease with a large variety of associated environmental risk factors, we
      suggest that current treatments combined with strategies that modulate the
      commensal microbiota would constitute a broader immunotherapeutic approach and
      improve the clinical outcome for MS patients.

PMID- 29191794
TI  - The antennae of damselfly larvae.
AB  - The larval antennal sensilla of two Zygoptera species, Calopteryx haemorroidalis
      (Calopterygidae) and Ischnura elegans (Coenagrionidae) are investigated with SEM
      and TEM. These two species have different antennae (geniculate, setaceous) and
      live in different environments (lotic, lentic waters). Notwithstanding this,
      similarities in the kind and distribution of sensilla are outlined: in both
      species the majority of sensilla types is located on the apical portion of the
      antenna, namely a composed coeloconic sensillum (possible chemoreceptor), two
      other coeloconic sensilla (possible thermo-hygroreceptors) and an apical seta
      (direct contact mechanoreceptor). Other mechanoreceptors, such as filiform hairs
      sensitive to movements of the surrounding medium or bristles positioned to sense
      the movements of the flagellar segments, are present on the antenna. Similarities
      in the antennal sensilla types and distribution are observed also with other
      dragonfly species, such as Onychogomphus forcipatus and Libellula depressa. A
      peculiar structure with an internal organization similar to that of a gland is
      observed in the apical antenna of C. haemorroidalis and I. elegans and it is
      present also in O. forcipatus and L. depressa. The possible function of this
      structure is at the moment unknown but deserves further investigations owing to
      its widespread presence in Odonata larvae.

PMID- 29191795
TI  - Glucan-MOS(r) improved growth and innate immunity in pacu stressed and
      experimentally infected with Aeromonas hydrophila.
AB  - We tested the efficacy of a commercial product (Glucan-MOS(r)) derived from yeast
      Saccharomyces cerevisiae, containing two combined products, beta-1,3-1,6 glucans
      and mannans on the growth, feed efficiency, stress and innate immune responses of
      juvenile pacu (Piaractus mesopotamicus) after a stressful handling and bacterial
      inoculation. For this, we evaluated the serum cortisol and plasma glucose levels,
      the respiratory activity of leukocytes, the serum lysozyme levels, as well as the
      number of circulating erythrocytes and leukocytes of fish fed during 30 days with
      diets containing increased levels of Glucan-MOS (0.0, 0.1, 0.2, 0.4 and 0.8%).
      The supplementation of 0.1% improved weight gain, feed conversion and the protein
      efficiency ratio compared to a control diet. The 0.2 and 0.4% Glucan-MOS(r) diets
      were sufficient to increase the respiratory burst of leukocytes and lysozyme
      activity, the number of thrombocytes, neutrophils and monocytes in the blood
      after a stressful handling and bacterial challenge, and minimized stress response
      as shown by decreased cortisol and glucose levels when compared to the control.
      The results of this work reinforce the benefits of the adoption of feeding
      strategies including combination of both beta-1,3-1,6 glucans and mannans as a
      dietary supplement in periods prior to intensive management. The 30-day period
      was sufficient to stimulate growth performance, improve nutrient utilization,
      minimize stress response and modulate innate immunity responses.

PMID- 29191796
TI  - De novo transcriptome assembly and analysis of differential gene expression
      following lipopolysaccharide challenge in Pelteobagrus fulvidraco.
AB  - The yellow catfish, Pelteobagrus fulvidraco, has been recognized as an important
      freshwater aquaculture species in Eastern and Southeast Asia. To gain a better
      understanding of the immune response in P. fulvidraco, we analyzed its
      transcriptome following stimulation with lipopolysaccharide (LPS). Phosphate
      buffer saline (PBS) was used as control. Following assembly and annotation,
      72,152 unigenes with an average length of 1090 bp were identified. A total of 370
      differentially expressed genes (DEGs) in the P. fulvidraco were observed at 12 h
      post LPS treatment, including 197 up-regulated genes and 173 down-regulated
      genes. Clusters of Orthologous Groups of proteins (KOG/COG) annotation
      demonstrated that a total of 18,819 unigenes classified into 26 categories. Gene
      ontology (GO) analysis revealed 20 biological process subcategories, 7 cellular
      component subcategories and 20 molecular function subcategories. The Kyoto
      Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified immune
      responses pathways. Quantitative reverse transcription polymerase chain reaction
      measured the expression of 18 genes involved in the immune response. CXCL2-like
      chemokine (CXCL2), goose-type lysozyme (LYZ G), and cathepsin K (CTSK) were
      significantly up-regulated. This study enriches the P. fulvidraco transcriptome
      database and provides insight into the immune response of P. fulvidraco against
      infection.

PMID- 29191797
TI  - Web-Based Intervention to Teach Developmentally Supportive Care to Parents of
      Preterm Infants: Feasibility and Acceptability Study.
AB  - BACKGROUND: Preterm birth affects 8% to 11% of the population and conveys a
      significant risk of developmental delays. Intervention programs that support
      child development have been shown to have a positive impact on early motor and
      cognitive development and on parental well-being. However, these programs are
      often difficult to implement in a real-life setting due to lack of resources.
      Hence, our multidisciplinary team developed Mieux Agir au Quotidien (MAQ) to
      teach developmentally supportive care to parents of preterm infants with the goal
      of improving child development and parental outcomes. Our intervention included 3
      in-person workshops that occurred prior to hospital discharge and a Web-based
      platform with written and videotaped materials that addressed 5 main themes: (1)
      infant behavioral cues, (2) flexion positioning; (3) oral feeding support, (4)
      parent-infant interactions, and (5) anticipation of developmental milestones.
      OBJECTIVE: This study aimed to test the feasibility and acceptability of the
      intervention by parents of preterm infants and assess clinical benefits on child
      neurodevelopment and parental outcomes during the first year of life. METHODS: A
      total of 107 infants born at <30 weeks and admitted to Sainte-Justine Hospital
      neonatal intensive care unit and their parents were enrolled in a nonrandomized
      controlled before-and-after interventional study (intervention n=55, comparison
      n=52). Acceptability of the program was assessed with a user satisfaction
      questionnaire. When the infants were at 4 months' corrected age, all parents
      completed questionnaires on infant temperament, parenting stress, sense of
      competence, and parenting satisfaction. At 12 months' corrected age,
      neurodevelopmental testing was performed on infants using the Alberta Infant
      Motor Scale and the Bayley Scales of Infant and Toddler Development, Third
      Edition. Comparisons between the 2 groups were done using independent t tests,
      Wilcoxon rank-sum tests, and Fisher exact tests. RESULTS: The majority of parents
      (43/45) were satisfied with the intervention program and all would recommend MAQ
      to others. MAQ met their need for evidence-based information that proved useful
      to support their child development. No difference in parental or child
      neurodevelopmental outcomes was detected in this pilot study for most outcomes
      except for higher median scores for parental coercive behaviors in the
      intervention group, although proportions scoring in the coercive range did not
      differ. CONCLUSIONS: Acceptability of the program was high among parents thus
      supporting the relevance of such intervention. A larger study using a randomized
      controlled trial design is needed to better document impact on parent and
      children and investigate how Web-based technologies can efficiently complement
      individualized intervention to alleviate the burden on health care resources.

PMID- 29191798
TI  - Using Android and Open Data Kit Technology in Data Management for Research in
      Resource-Limited Settings in the Niger Delta Region of Nigeria: Cross-Sectional
      Household Survey.
AB  - BACKGROUND: Data collection in Sub-Saharan Africa has traditionally been paper
      based. However, the popularization of Android mobile devices and data capture
      software has brought paperless data management within reach. We used Open Data
      Kit (ODK) technology on Android mobile devices during a household survey in the
      Niger Delta region of Nigeria. OBJECTIVE: The aim of this study was to describe
      the pros and cons of deploying ODK for data management. METHODS: A descriptive
      cross-sectional household survey was carried out by 6 data collectors between
      April and May 2016. Data were obtained from 1706 persons in 601 households across
      6 communities in 3 states in the Niger Delta. The use of Android mobile devices
      and ODK technology involved form building, testing, collection, aggregation, and
      download for data analysis. The median duration for data collection per household
      and per individual was 25.7 and 9.3 min, respectively. RESULTS: Data entries per
      device ranged from 33 (33/1706, 1.93%) to 482 (482/1706, 28.25%) individuals
      between 9 (9/601, 1.5%) and 122 (122/601, 20.3%) households. The most entries
      (470) were made by data collector 5. Only 2 respondents had data entry errors
      (2/1706, 0.12%). However, 73 (73/601, 12.1%) households had inaccurate date and
      time entries for when data collection started and ended. The cost of deploying
      ODK was estimated at US $206.7 in comparison with the estimated cost of US $466.7
      for paper-based data management. CONCLUSIONS: We found the use of mobile data
      capture technology to be efficient and cost-effective. As Internet services
      improve in Africa, we advocate their use as effective tools for health
      information management.

PMID- 29191801
TI  - Inspectors voice concern over independent residential detox units.

PMID- 29191799
TI  - Implementation of a Web-Based Organ Donation Educational Intervention:
      Development and Use of a Refined Process Evaluation Model.
AB  - BACKGROUND: The lack of available organs is often considered to be the single
      greatest problem in transplantation today. Internet use is at an all-time high,
      creating an opportunity to increase public commitment to organ donation through
      the broad reach of Web-based behavioral interventions. Implementing Internet
      interventions, however, presents challenges including preventing fraudulent
      respondents and ensuring intervention uptake. Although Web-based organ donation
      interventions have increased in recent years, process evaluation models
      appropriate for Web-based interventions are lacking. OBJECTIVE: The aim of this
      study was to describe a refined process evaluation model adapted for Web-based
      settings and used to assess the implementation of a Web-based intervention aimed
      to increase organ donation among African Americans. METHODS: We used a randomized
      pretest-posttest control design to assess the effectiveness of the intervention
      website that addressed barriers to organ donation through corresponding videos.
      Eligible participants were African American adult residents of Georgia who were
      not registered on the state donor registry. Drawing from previously developed
      process evaluation constructs, we adapted reach (the extent to which individuals
      were found eligible, and participated in the study), recruitment (online
      recruitment mechanism), dose received (intervention uptake), and context (how the
      Web-based setting influenced study implementation) for Internet settings and used
      the adapted model to assess the implementation of our Web-based intervention.
      RESULTS: With regard to reach, 1415 individuals completed the eligibility
      screener; 948 (67.00%) were determined eligible, of whom 918 (96.8%) completed
      the study. After eliminating duplicate entries (n=17), those who did not initiate
      the posttest (n=21) and those with an invalid ZIP code (n=108), 772 valid entries
      remained. Per the Internet protocol (IP) address analysis, only 23 of the 772
      valid entries (3.0%) were within Georgia, and only 17 of those were considered
      unique entries and could be considered for analyses. With respect to recruitment,
      517 of the 772 valid entries (67.0%) of participants were recruited from a Web
      recruiter. Regarding dose received, no videos from the intervention website were
      watched in their entirety, and the average viewing duration was 17 seconds over
      the minimum. With respect to context, context analysis provided us with valuable
      insights into factors in the Internet environment that may have affected study
      implementation. Although only active for a brief period of time, the Craigslist
      website advertisement may have contributed the largest volume of fraudulent
      responses. CONCLUSIONS: We determined fraud and low uptake to be serious threats
      to this study and further confirmed the importance of conducting a process
      evaluation to identify such threats. We suggest checking participants' IP
      addresses before study initiation, selecting software that allows for automatic
      duplicate protection, and tightening minimum requirements for intervention
      uptake. Further research is needed to understand how process evaluation models
      can be used to monitor implementation of Web-based studies.

PMID- 29191800
TI  - Implementation Intention and Reminder Effects on Behavior Change in a Mobile
      Health System: A Predictive Cognitive Model.
AB  - BACKGROUND: Implementation intentions are mental representations of simple plans
      to translate goal intentions into behavior under specific conditions. Studies
      show implementation intentions can produce moderate to large improvements in
      behavioral goal achievement. Human associative memory mechanisms have been
      implicated in the processes by which implementation intentions produce effects.
      On the basis of the adaptive control of thought-rational (ACT-R) theory of
      cognition, we hypothesized that the strength of implementation intention effect
      could be manipulated in predictable ways using reminders delivered by a mobile
      health (mHealth) app. OBJECTIVE: The aim of this experiment was to manipulate the
      effects of implementation intentions on daily behavioral goal success in ways
      predicted by the ACT-R theory concerning mHealth reminder scheduling. METHODS: An
      incomplete factorial design was used in this mHealth study. All participants were
      asked to choose a healthy behavior goal associated with eat slowly, walking, or
      eating more vegetables and were asked to set implementation intentions. N=64
      adult participants were in the study for 28 days. Participants were stratified by
      self-efficacy and assigned to one of two reminder conditions: reminders-presented
      versus reminders-absent. Self-efficacy and reminder conditions were crossed.
      Nested within the reminders-presented condition was a crossing of frequency of
      reminders sent (high, low) by distribution of reminders sent (distributed,
      massed). Participants in the low frequency condition got 7 reminders over 28
      days; those in the high frequency condition were sent 14. Participants in the
      distributed conditions were sent reminders at uniform intervals. Participants in
      the massed distribution conditions were sent reminders in clusters. RESULTS:
      There was a significant overall effect of reminders on achieving a daily
      behavioral goal (coefficient=2.018, standard error [SE]=0.572, odds ratio
      [OR]=7.52, 95% CI 0.9037-3.2594, P<.001). As predicted by ACT-R, using default
      theoretical parameters, there was an interaction of reminder frequency by
      distribution on daily goal success (coefficient=0.7994, SE=0.2215, OR=2.2242, 95%
      CI 0.3656-1.2341, P<.001). The total number of times a reminder was acknowledged
      as received by a participant had a marginal effect on daily goal success
      (coefficient=0.0694, SE=0.0410, OR=1.0717, 95% CI -0.01116 to 0.1505, P=.09), and
      the time since acknowledging receipt of a reminder was highly significant
      (coefficient=-0.0490, SE=0.0104, OR=0.9522, 95% CI -0.0700 to -0.2852], P<.001).
      A dual system ACT-R mathematical model was fit to individuals' daily goal
      successes and reminder acknowledgments: a goal-striving system dependent on
      declarative memory plus a habit-forming system that acquires automatic procedures
      for performance of behavioral goals. CONCLUSIONS: Computational cognitive theory
      such as ACT-R can be used to make precise quantitative predictions concerning
      daily health behavior goal success in response to implementation intentions and
      the dosing schedules of reminders.

PMID- 29191803
TI  - Dasatinib Approved for Pediatric CML.
AB  - The FDA approved dasatinib to treat pediatric chronic myeloid leukemia. This drug
      is the second tyrosine kinase inhibitor, alongside imatinib, approved for this
      indication and represents an important new option for first- and second-line
      treatment.

PMID- 29191802
TI  - Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights
      into Acute Injury and Long-term Recovery.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability
      in cancer survivors. CIPN investigations in preclinical model systems have
      focused on either behaviors or acute changes in nerve conduction velocity (NCV)
      and amplitude, but greater understanding of the underlying nature of axonal
      injury and its long-term processes is needed as cancer patients live longer. In
      this study, we used multiple independent endpoints to systematically characterize
      CIPN recovery in mice exposed to the antitubulin cancer drugs eribulin,
      ixabepilone, paclitaxel, or vinorelbine at MTDs. All of the drugs ablated
      intraepidermal nerve fibers and produced axonopathy, with a secondary disruption
      in myelin structure within 2 weeks of drug administration. In addition, all of
      the drugs reduced sensory NCV and amplitude, with greater deficits after
      paclitaxel and lesser deficits after ixabepilone. These effects correlated with
      degeneration in dorsal root ganglia (DRG) and sciatic nerve and abundance of
      Schwann cells. Although most injuries were fully reversible after 3-6 months
      after administration of eribulin, vinorelbine, and ixabepilone, we observed
      delayed recovery after paclitaxel that produced a more severe, pervasive, and
      prolonged neurotoxicity. Compared with other agents, paclitaxel also displayed a
      unique prolonged exposure in sciatic nerve and DRG. The most sensitive indicator
      of toxicity was axonopathy and secondary myelin changes accompanied by a
      reduction in intraepidermal nerve fiber density. Taken together, our findings
      suggest that intraepidermal nerve fiber density and changes in NCV and amplitude
      might provide measures of axonal injury to guide clinical practice.Significance:
      This detailed preclinical study of the long-term effects of widely used
      antitubulin cancer drugs on the peripheral nervous system may help guide clinical
      evaluations to improve personalized care in limiting neurotoxicity in cancer
      survivors. Cancer Res; 78(3); 817-29. (c)2017 AACR.

PMID- 29191804
TI  - Appropriate training in eating disorders could save many lives.

PMID- 29191805
TI  - MPs demand to know why government restricted meningitis B vaccine to infants
      under 1.

PMID- 29191806
TI  - Atrial fibrillation prevention: an appraisal of current evidence.
AB  - Atrial fibrillation (AF), which is the most diagnosed arrhythmia, is becoming a
      significant issue for health policy-makers. In particular, more and more
      attention is being devoted to AF prevention. Indeed, several studies recently
      published point out how targeted interventions could be useful in reducing the
      risk of AF occurrence (or recurrence). In this review, we briefly summarised the
      role of the major risk factors associated with the incidence of AF, as well as
      the effectiveness of interventions aimed at controlling these risk factors.
      Several general risk factors, such as alcohol consumption, physical activity,
      smoking habit, as well as specific cardiovascular risk factors as diabetes
      mellitus, hypertension and obesity have a relevant impact in determining the
      occurrence of AF, along with a strong clinical evidence of a dose-effect response
      mechanism for most of the factors examined. Specific interventions aimed at
      controlling risk factors have been showed to clearly reduce the risk of AF in
      several cohorts. Even more importantly, integrated programmes aimed at
      controlling for multiple risk factors would be more efficient in terms of
      reducing risk of AF, in particular whena stricter control is observed. AF
      prevention requires a series of initiatives focused on the many risk factors that
      we reviewed, as well as a more integrated approach, which should involve many
      stakeholders at different levels. In this light and also considering the
      constantly changing epidemiology, AF prevention may constitute a future 'win-win'
      strategy for all the stakeholders.

PMID- 29191807
TI  - DNA Methyltransferase 1-Dependent DNA Hypermethylation Constrains Arteriogenesis
      by Augmenting Shear Stress Set Point.
AB  - BACKGROUND: Arteriogenesis is initiated by increased shear stress and is thought
      to continue until shear stress is returned to its original "set point." However,
      the molecular mechanism(s) through which shear stress set point is established by
      endothelial cells (ECs) are largely unstudied. Here, we tested the hypothesis
      that DNA methyltransferase 1 (DNMT1)-dependent EC DNA methylation affects
      arteriogenic capacity via adjustments to shear stress set point. METHODS AND
      RESULTS: In femoral artery ligation-operated C57BL/6 mice, collateral artery
      segments exposed to increased shear stress without a change in flow direction
      (ie, nonreversed flow) exhibited global DNA hypermethylation (increased 5
      methylcytosine staining intensity) and constrained arteriogenesis (30% less
      diameter growth) when compared with segments exposed to both an increase in shear
      stress and reversed-flow direction. In vitro, ECs exposed to a flow waveform
      biomimetic of nonreversed collateral segments in vivo exhibited a 40% increase in
      DNMT1 expression, genome-wide hypermethylation of gene promoters, and a DNMT1
      dependent 60% reduction in proarteriogenic monocyte adhesion compared with ECs
      exposed to a biomimetic reversed-flow waveform. These results led us to test
      whether DNMT1 regulates arteriogenic capacity in vivo. In femoral artery ligation
      operated mice, DNMT1 inhibition rescued arteriogenic capacity and returned shear
      stress back to its original set point in nonreversed collateral segments.
      CONCLUSIONS: Increased shear stress without a change in flow direction initiates
      arteriogenic growth; however, it also elicits DNMT1-dependent EC DNA
      hypermethylation. In turn, this diminishes mechanosensing, augments shear stress
      set point, and constrains the ultimate arteriogenic capacity of the vessel. This
      epigenetic effect could impact both endogenous collateralization and treatment of
      arterial occlusive diseases.

PMID- 29191808
TI  - Suberanilohydroxamic Acid as a Pharmacological Kruppel-Like Factor 2 Activator
      That Represses Vascular Inflammation and Atherosclerosis.
AB  - BACKGROUND: Kruppel-like factor 2 (KLF2) is an important zinc-finger
      transcription factor that maintains endothelial homeostasis by its anti
      inflammatory, -thrombotic, -oxidative, and -proliferative effects in endothelial
      cells. In light of the potent vasoprotective effects of KLF2, modulating KLF2
      expression or function could give rise to new therapeutic strategies to treat
      cardiovascular diseases. METHODS AND RESULTS: High-throughput drug screening
      based on KLF2 promoter luciferase reporter assay was performed to screen KLF2
      activators. Real-time PCR and western blot were used to detect gene and protein
      expression. Identified KLF2 activator was orally administered to ApoE-/- mice to
      evaluate anti-atherosclerotic efficacy. By screening 2400 compounds in the
      Spectrum library, we identified suberanilohydroxamic (SAHA) acid, also known as
      vorinostat as a pharmacological KLF2 activator through myocyte enhancer factor 2.
      We found that SAHA exhibited anti-inflammatory effects and attenuated monocyte
      adhesion to endothelial cells inflamed with tumor necrosis factor alpha. We
      further showed that the inhibitory effect of SAHA on endothelial inflammation and
      ensuing monocyte adhesion was KLF2 dependent using KLF2-deficient mouse lung
      endothelial cells or KLF2 small interfering RNA- depleted human endothelial
      cells. Importantly, we observed that oral administration of SAHA reduced diet
      induced atherosclerotic lesion development in ApoE-/- mice without significant
      effect on serum lipid levels. CONCLUSIONS: These results demonstrate that SAHA
      has KLF2-dependent anti-inflammatory effects in endothelial cells and provide the
      proof of concept that KLF2 activation could be a promising therapeutic strategy
      for treating atherosclerosis.

PMID- 29191810
TI  - Can neonatal staff site EEG leads in the correct position? A pilot study.

PMID- 29191809
TI  - Molecular Fingerprint for Terminal Abdominal Aortic Aneurysm Disease.
AB  - BACKGROUND: Clinical decision making in abdominal aortic aneurysms (AAA) relies
      completely on diameter. At this point, improved decision tools remain an unmet
      medical need. Our goal was to identify changes at the molecular level
      specifically leading up to AAA rupture. METHODS AND RESULTS: Aortic wall tissue
      specimens were collected during open elective (eAAA; n=31) or emergency repair of
      ruptured AAA (rAAA; n=17), and gene expression was investigated using
      microarrays. Identified candidate genes were validated with quantitative real
      time polymerase chain reaction in an independent sample set (eAAA: n=46; rAAA:
      n=18). Two gene sets were identified, 1 set containing 5 genes linked to terminal
      progression, that is, positively associated with progression of larger AAA, and
      with rupture (HILPDA, ANGPTL4, LOX, SRPX2, FCGBP), and a second set containing 5
      genes exclusively upregulated in rAAA (ADAMTS9, STC1, GFPT2, GAL3ST4, CCL4L1).
      Genes in both sets essentially associated with processes related to impaired
      tissue remodeling, such as angiogenesis and adipogenesis. In gene expression
      experiments we were able to show that upregulated gene expression for identified
      candidate genes is unique for AAA. Functionally, the selected upregulated factors
      converge at processes coordinated by the canonical HIF-1alpha signaling pathway
      and are highly expressed in fibroblasts but not inflammatory cells of the
      aneurysmatic wall. Histological quantification of angiogenesis and exploration of
      the HIF-1alpha network in rAAA versus eAAA shows enhanced microvessel density but
      also clear activation of the HIF-1alpha network in rAAA. CONCLUSIONS: Our study
      shows a specific molecular fingerprint for terminal AAA disease. These changes
      appear to converge at activation of HIF-1alpha signaling in mesenchymal cells.
      Aspects of this cascade might represent targets for rupture risk assessment.

PMID- 29191811
TI  - Neonatal mannequin comparison of the Upright self-inflating bag and snap-fit mask
      versus standard resuscitators and masks: leak, applied load and tidal volumes.
AB  - OBJECTIVE: Neonatal mask ventilation is a difficult skill to acquire and
      maintain. Mask leak is common and can lead to ineffective ventilation. The aim of
      this study was to determine whether newly available neonatal self-inflating bags
      and masks could reduce mask leak without additional load being applied to the
      face. DESIGN: Forty operators delivered 1 min episodes of mask ventilation to a
      mannequin using the Laerdal Upright Resuscitator, a standard Laerdal infant
      resuscitator (Laerdal Medical) and a T-Piece Resuscitator (Neopuff), using both
      the Laerdal snap-fit face mask and the standard Laerdal size 0/1 face mask
      (equivalent sizes). Participants were asked to use pressure sufficient to achieve
      'appropriate' chest rise. Leak, applied load, airway pressure and tidal volume
      were measured continuously. Participants were unaware that load was being
      recorded. RESULTS: There was no difference in mask leak between resuscitation
      devices. Leak was significantly lower when the snap-fit mask was used with all
      resuscitation devices, compared with the standard mask (14% vs 37% leak, P<0.01).
      The snap-fit mask was preferred by 83% of participants. The device-mask
      combinations had no significant effect on applied load. CONCLUSIONS: The Laerdal
      Upright Resuscitator resulted in similar leak to the other resuscitation devices
      studied, and did not exert additional load to the face and head. The snap-fit
      mask significantly reduced overall leak with all resuscitation devices and was
      the mask preferred by participants.

PMID- 29191812
TI  - Physiologically based cord clamping stabilises cardiac output and reduces
      cerebrovascular injury in asphyxiated near-term lambs.
AB  - BACKGROUND: Physiologically based cord clamping (PBCC) has advantages over
      immediate cord clamping (ICC) during preterm delivery, but its efficacy in
      asphyxiated infants is not known. We investigated the physiology of PBCC
      following perinatal asphyxia in near-term lambs. METHODS: Near-term sheep fetuses
      (139+/-2 (SD) days' gestation) were instrumented to measure umbilical, carotid,
      pulmonary and femoral arterial flows and pressures. Systemic and cerebral
      oxygenation was recorded using pulse oximetry and near-infrared spectroscopy,
      respectively. Fetal asphyxia was induced until mean blood pressure reached ~20 mm
      Hg, where lambs underwent ICC and initiation of ventilation (n=7), or ventilation
      for 15 min prior to umbilical cord clamping (PBCC; n=8). Cardiovascular
      parameters were measured and white and grey matter microvascular integrity
      assessed using qRT-PCR and immunohistochemistry. RESULTS: PBCC restored
      oxygenation and cardiac output at the same rate and in a similar fashion to lambs
      resuscitated following ICC. However, ICC lambs had a rapid and marked overshoot
      in mean systemic arterial blood pressure from 1 to 10 min after ventilation
      onset, which was largely absent in PBCC lambs. ICC lambs had increased
      cerebrovascular injury, as indicated by reduced expression of blood-brain barrier
      proteins and increased cerebrovascular protein leakage in the subcortical white
      matter (by 86%) and grey matter (by 47%). CONCLUSION: PBCC restored cardiac
      output and oxygenation in an identical time frame as ICC, but greatly mitigated
      the postasphyxia rebound hypertension measured in ICC lambs. This likely
      protected the asphyxiated brain from cerebrovascular injury. PBCC may be a more
      suitable option for the resuscitation of the asphyxiated newborn compared with
      the current standard of ICC.

PMID- 29191813
TI  - Use of clear sterile drapes for invasive procedures.

PMID- 29191814
TI  - Individual and partnership factors associated with anticipated versus actual
      partner notification following STI diagnosis among men who have sex with men
      and/or with transgender women in Lima, Peru.
AB  - OBJECTIVES: A detailed understanding of intentions and practices related to
      partner notification (PN) following STI diagnosis can improve control strategies.
      We assessed participant-level and partner-level factors guiding notification
      behaviour among men who have sex with men and/or with transgender women (MSM-TW)
      in Lima, Peru, including discordances between anticipated and actual
      notification. METHODS: Men newly diagnosed with gonorrhoea, chlamydia and/or
      syphilis between 2012 and 2014 reported recent partners' characteristics,
      anticipated PN practices, and actual PN outcomes following diagnosis. Generalised
      estimating equation Poisson regression analyses assessed factors guiding PN
      outcomes. RESULTS: Participants (n=150) predominantly identified as homosexual
      (70%) and moderno (versatile sexual role, 55%); 55% of partners (n=402) were
      casual. Among all sexual partners, 35% were notified of the STI diagnosis, though
      only 51% of predicted PN occurred and 26% of actual notifications were
      unanticipated. 47% of participants notified no partners, while 24% notified all
      partners. PN was more common with stable versus casual (adjusted prevalence ratio
      (aPR), 95% CI: 0.53, 0.39 to 0.73) or commercial (aPR, 95% CI: 0.38, 0.12 to
      1.21) partners, and among participants who perceived PN as normative among their
      peers (aPR, 95% CI: 1.96, 1.37 to 2.82). A trend towards greater notification
      following condom-protected intercourse was observed (aPR, 95% CI: 1.33, 0.98 to
      1.81). PN frequency did not differ by type of STI diagnosed.Anticipated
      notification predicted actual notification (aPR, 95% CI: 1.67, 1.19 to 2.33) only
      imperfectly: 81 (54%) participants' PN practices did not match their anticipated
      behaviour. Successful notification despite anticipated silence (40 participants,
      63 partners) was associated with stable partnerships and a normative perception
      of PN. Non-notification despite intention (43 participants, 73 partners)
      frequently occurred among participants reporting exclusively oral sex with the
      partner or with partners identified as activo (insertive role). CONCLUSIONS:
      Anticipated notification imperfectly reflects actual PN behaviour. Future
      interventions to improve PN among MSM-TW in Peru need to acknowledge partnership
      contexts.

PMID- 29191817
TI  - Seven days in medicine: 22-28 November 2017.

PMID- 29191815
TI  - Sexual relationships, intimate partner violence and STI partner notification in
      Cape Town, South Africa: an observational study.
AB  - OBJECTIVES: We aimed to identify individual and sexual partnership
      characteristics associated with partner notification (PN) among people with STI.
      We hypothesised that PN would be less likely in more casual sexual partnerships
      and in partnerships with intimate partner violence (IPV). METHODS: We conducted
      an observational study among the first 330 patients with STI enrolled in a trial
      of a behavioural intervention to reduce STI incidence, at a clinic in a poor,
      Cape Town community. We included 195 index patients (those reporting STI
      symptoms), and conducted longitudinal analyses using participant-completed
      questionnaires on the day of diagnosis and 2 weeks later. Using partnership data
      for five recent sexual partners, we assessed factors associated with reported PN
      with logistic regressions, adjusting for repeated measurements on the same
      participant for each partner. RESULTS: The sample included 99 males with 303
      partners and 96 females with 158 partners. Males reported perpetrating IPV in
      46.2% of partnerships. Females reported being IPV victims in 53.2% of
      partnerships. Males notified 58.1%, females 75.4% of partners during the 2 weeks
      following diagnosis. Type of partner was an independent correlate of PN for males
      and females, with the odds of PN lower in more casual partnerships. For males,
      reporting physical IPV perpetration in the partnership was an independent
      correlate of PN. For females, there was no association between IPV victimisation
      in a partnership and PN. CONCLUSIONS: Efforts to decrease the pool of infectious
      partners need to have a strong focus on the promotion of PN in casual
      relationships and one-night stands. IPV was not identified as a barrier to PN. In
      future, we need to investigate the association between IPV with an objective
      measure of PN success such as partner testing or treatment, or index patient
      reinfection. CLINICAL TRIAL REGISTRATION: PACTR201606001682364; Pre-results.

PMID- 29191816
TI  - Clinical factors associated with syphilis concordance in men in sexual
      partnerships: a cross-sectional couples study.
AB  - BACKGROUND: Syphilis infections continue to increase among men who have sex with
      men (MSM) in many countries, with rates often higher among HIV-positive MSM.
      There is limited understanding of the risk and determinants of syphilis
      transmission between men. We aimed to examine the concordance of early syphilis
      infection between male sexual partners and clinical factors associated with
      transmission. METHODS: Men attending Melbourne Sexual Health Centre with their
      male partners, where at least one was diagnosed with early syphilis, were
      identified from linkage of partner records between March 2011 and April 2016.
      Early latent syphilis was defined as a new asymptomatic syphilis presentation of
      less than 2 years' duration. Associations between concordance and potential risk
      factors were examined using Fisher's exact test. RESULTS: Among 43 couples (86
      men) identified, there were 13 couples (26 men) where both were diagnosed with
      early syphilis, representing a concordance rate of 30.2% (95% CI 17.2% to 46.1%).
      Among the 13 concordant couples, 5 men had primary syphilis (4 penile, 1 anal),
      11 secondary syphilis (8 generalised rash, 3 penile, 2 anal, 1 oral lesion) and
      10 early latent infections. Concordance was higher among couples where at least
      one partner had secondary syphilis compared with couples where neither partner
      had secondary syphilis (53% (9/17) vs 15% (4/26), P=0.016). Furthermore,
      concordance was higher among couples where one was HIV positive compared with
      couples where both were HIV negative (62% (5/8) vs 23% (8/35), P=0.042).
      CONCLUSIONS: There was an overall concordance rate of 30%. Higher concordance
      rates for early syphilis infection between male sexual partners were associated
      with HIV and secondary syphilis.

PMID- 29191818
TI  - Sterol 27-hydroxylase gene dosage and the antiatherosclerotic effect of
      Rifampicin in mice.
AB  - Sterol 27-hydroxylase (CYP27A1) catalyzes the hydroxylation of cholesterol to 27
      hydroxycholesterol (27-OHC) and regulates cholesterol homeostasis. In Cyp27a1/
      Apolipoprotein E (ApoE) double knockout (KO) mice fed with Western diet (WD), the
      atherosclerotic phenotype found in ApoE KO mice was reversed. As protective
      mechanism, up-regulation of Cyp3a11 and Cyp7a1 was proposed. Cyp27a1
      heterozygote/ApoE KO (het) mice, with reduced Cyp27a1 expression and normal
      levels of Cyp7a1 and Cyp3a11, developed more severe lesions than ApoE KO mice. To
      analyze the contribution of Cyp3a11 to the protection of atherosclerosis
      development, Cyp3a11 was induced by Rifampicin (RIF) in ApoE KO and het mice.
      Males were fed with WD and treated daily with RIF (10 mg/kg ip) or vehicle for 4
      weeks. Atherosclerosis was quantified in the aortic valve. Plasma lipids and 27
      hydroxycholesterol (27-OHC), expression of cytochromes P450 and genes involved in
      cholesterol transport and bile acids (BAs) signaling in liver and intestine, and
      intestinal cholesterol absorption were analyzed. RIF increased expression of
      hepatic but not intestinal Cyp3a11 4-fold in both genotypes. In ApoE KO mice
      treated with RIF, we found a 2-fold decrease in plasma cholesterol, and a 2-fold
      increase in high-density lipoprotein/low-density lipoprotein ratio and CY27A1
      activity. Intestinal cholesterol absorption remained unchanged and
      atherosclerotic lesions decreased approximately 3-fold. In het mice, RIF had no
      effect on plasma lipids composition, CYP27A1 activity, and atherosclerotic plaque
      development, despite a reduction in cholesterol absorption. In conclusion, the
      antiatherogenic effect of Cyp3a11 induction by RIF was also dependent on Cyp27a1
      expression.

PMID- 29191819
TI  - Efficacy and safety of tocilizumab in patients with refractory Takayasu
      arteritis: results from a randomised, double-blind, placebo-controlled, phase 3
      trial in Japan (the TAKT study).
AB  - OBJECTIVE: To investigate the efficacy and safety of the interleukin-6 receptor
      antibody tocilizumab in patients with Takayasu arteritis (TAK). METHODS: Patients
      with TAK who had relapsed within the previous 12 weeks were induced into
      remission with oral glucocorticoid therapy. In this double-blind, placebo
      controlled trial, patients were randomly assigned 1:1 to receive weekly
      tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were
      tapered 10 %/week from week 4 to a minimum of 0.1 mg/kg/day until 19 patients
      relapsed. The primary endpoint was time to relapse of TAK, defined as >=2 of the
      following: objective systemic symptoms, subjective systemic symptoms, elevated
      inflammation markers, vascular signs and symptoms or ischaemic symptoms. RESULTS:
      The intent-to-treat and safety populations included 18 tocilizumab-treated and 18
      placebo-treated patients. The per-protocol set (PPS) included 16 tocilizumab
      treated and 17 placebo-treated patients. HRs for time to relapse of TAK were 0.41
      (95.41% CI 0.15 to 1.10; p=0.0596) in the intent-to-treat population (primary
      endpoint) based on relapse in eight tocilizumab-treated and 11 placebo-treated
      patients and 0.34 (95.41% CI 0.11 to 1.00; p=0.0345) in the PPS. The secondary
      endpoints, time to relapse assessed by Kerr's definition and clinical symptoms
      only, were consistent with the primary endpoint. Serious adverse events were
      reported in one tocilizumab-treated and two placebo-treated patients. There were
      no serious infections and no deaths. CONCLUSION: Although the primary endpoint
      was not met, the results suggest favour for tocilizumab over placebo for time to
      relapse of TAK without new safety concerns. Further investigation is warranted to
      confirm the efficacy of tocilizumab in patients with refractory TAK. TRIAL
      REGISTRATION NUMBER: JapicCTI-142616.

PMID- 29191821
TI  - Follicular bronchiolitis in an HIV-infected individual on combination
      antiretroviral therapy with low CD4+ cell count but sustained viral suppression.
AB  - A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis
      pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/uL; viral load: 518 000
      copies/mL). He initiated combination antiretroviral therapy. Later that year, he
      was also diagnosed with granulomatosis with polyangiitis and was treated with
      prednisolone. Despite complete viral suppression and increasing CD4+ count (162
      cells/uL), he was readmitted with PCP in April 2015. Subsequently, he returned to
      Denmark (CD4+ count: 80 cells/uL, viral suppression). Over the following months,
      he developed progressive dyspnoea. Lung function tests demonstrated severely
      reduced lung capacity with an obstructive pattern and a moderately reduced
      diffusion capacity. High resolution computer tomography revealed minor areas with
      tree-in-bud pattern and no signs of air trapping on expiratory views. Lung biopsy
      showed lymphocytic infiltration surrounding the bronchioles with sparing of the
      alveolar septa. He was diagnosed with follicular bronchiolitis. The patient
      spontaneously recovered along with an improvement of the immune system.

PMID- 29191820
TI  - Monocyte alterations in rheumatoid arthritis are dominated by preterm release
      from bone marrow and prominent triggering in the joint.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) accompanies infiltration and activation of
      monocytes in inflamed joints. We investigated dominant alterations of RA
      monocytes in bone marrow (BM), blood and inflamed joints. METHODS: CD14+ cells
      from BM and peripheral blood (PB) of patients with RA and osteoarthritis (OA)
      were profiled with GeneChip microarrays. Detailed functional analysis was
      performed with reference transcriptomes of BM precursors, monocyte blood subsets,
      monocyte activation and mobilisation. Cytometric profiling determined monocyte
      subsets of CD14++CD16-, CD14++CD16+ and CD14+CD16+ cells in BM, PB and synovial
      fluid (SF) and ELISAs quantified the release of activation markers into SF and
      serum. RESULTS: Investigation of genes differentially expressed between RA and OA
      monocytes with reference transcriptomes revealed gene patterns of early myeloid
      precursors in RA-BM and late myeloid precursors along with reduced terminal
      differentiation to CD14+CD16+monocytes in RA-PB. Patterns associated with tumor
      necrosis factor/lipopolysaccharide (TNF/LPS) stimulation were weak and more
      pronounced in RA-PB than RA-BM. Cytometric phenotyping of cells in BM, blood and
      SF disclosed differences related to monocyte subsets and confirmed the reduced
      frequency of terminally differentiated CD14+CD16+monocytes in RA-PB. Monocyte
      activation in SF was characterised by the predominance of CD14++CD16++CD163+HLA
      DR+ cells and elevated concentrations of sCD14, sCD163 and S100P. CONCLUSION:
      Patterns of less mature and less differentiated RA-BM and RA-PB monocytes suggest
      increased turnover with accelerated monocytopoiesis, BM egress and migration into
      inflamed joints. Predominant activation in the joint indicates the action of
      local and primary stimuli, which may also promote adaptive immune triggering
      through monocytes, potentially leading to new diagnostic and therapeutic
      strategies.

PMID- 29191823
TI  - Lyric hearing aid: a rare cause of benign necrotising otitis externa/external ear
      canal cholesteatoma.
AB  - An 80-year-old Caucasian man presented with an incidental and asymptomatic lesion
      in his right ear thought to be secondary to his use of hearing aids for
      presbycusis. He used Lyric hearing aids, designed for 24 hours-a-day use for 4
      months at a time and had no other previous otological problems. He underwent a
      bony meatoplasty and vascular flap reconstruction via a retroauricular approach
      to remove the lesion for histological analysis and regrafting of the area. The
      lesion was confirmed on histopathology as an ear canal cholesteatoma.

PMID- 29191822
TI  - Systemic thrombolysis in a patient with massive pulmonary embolism and recent
      glioblastoma multiforme resection.
AB  - While trials of systemic thrombolysis for submassive and massive pulmonary
      embolism (PE) report intracranial haemorrhage (ICH) rates of 2%-3%, the risk of
      ICH in patients with recent brain surgery or intracranial neoplasm is unknown
      since these patients were excluded from these trials. We report a case of massive
      PE treated with systemic thrombolysis in a patient with recent neurosurgery for
      an intracranial neoplasm. We discuss the risks and benefits of systemic
      thrombolysis for massive PE in the context of previous case reports, prior cohort
      studies and trials, and current guidelines. There may be times when the immediate
      risk of death from massive PE outweighs the risk of ICH from systemic
      thrombolysis, even when guideline-listed major contraindications exist. This case
      provides an example of how the haemodynamic benefit of systemic thrombolysis
      outweighed the impact of ICH in a patient who had undergone recent neurosurgical
      resection of a glioblastoma multiforme tumour.

PMID- 29191825
TI  - State of Victoria will allow voluntary euthanasia from mid 2019.

PMID- 29191824
TI  - Primary cutaneous mucoepidermal carcinoma.
AB  - Mucoepidermal carcinoma (MEC) is a tumour having mixed components of mucus
      secreting and epidermoid cells. Salivary glands are the the most common site of
      origin. Primary cutaneous MEC is a rare presentation. We report a primary
      cutaneous MEC in a 98-year-old woman presenting a noduloulcerative lesion over
      the dorsum of the nose. Histopathology of the tumour showed nests of epidermoid
      cells with glandular differentiation and mucin production. The diagnosis was
      confirmed by immunohistochemistry.

PMID- 29191826
TI  - Not All Aseptic Meningitis Is Created Equal.

PMID- 29191827
TI  - Proteasome-mediated degradation of collagen III by cortisol in amnion
      fibroblasts.
AB  - Rupture of fetal membranes (ROM) can initiate parturition at both term and
      preterm. Collagen III in the compact layer of the amnion contributes to the
      tensile strength of fetal membranes. However, the upstream signals triggering
      collagen III degradation remain mostly elusive. In this study, we investigated
      the role of cortisol regenerated by 11beta-hydroxysteroid dehydrogenase 1 (11beta
      HSD1) in collagen III degradation in human amnion fibroblasts with an aim to seek
      novel targets for the prevention of preterm premature ROM (pPROM)-elicited
      preterm birth. Human amnion tissue and cultured amnion tissue explants and amnion
      fibroblasts were used to study the regulation of collagen III, which is composed
      of three identical 3alpha 1 chains (COL3A1), by cortisol. Cortisol decreased
      COL3A1 protein but not mRNA abundance in a concentration-dependent manner.
      Cortisone also decreased COL3A1 protein, which was blocked by 11beta-HSD1
      inhibition. The reduction in COL3A1 protein by cortisol was not affected by a
      transcription inhibitor but was further enhanced by a translation inhibitor.
      Autophagic pathway inhibitor chloroquine or siRNA-mediated knock-down of ATG7, an
      essential protein for autophagy, failed to block cortisol-induced reduction in
      COL3A1 protein abundance, whereas proteasome pathway inhibitors MG132 and
      bortezomib significantly attenuated cortisol-induced reduction in COL3A1 protein
      abundance. Moreover, cortisol increased COL3A1 ubiquitination and the reduction
      of COL3A1 protein by cortisol was blocked by PYR-41, a ubiquitin-activating
      enzyme inhibitor. Conclusively, cortisol regenerated in amnion fibroblasts may be
      associated with ROM at parturition by reducing collagen III protein abundance
      through a ubiquitin-proteasome pathway.

PMID- 29191828
TI  - Hydrogen-deuterium exchange reveals long-range dynamical allostery in soybean
      lipoxygenase.
AB  - In lipoxygenases, the topologically conserved C-terminal domain catalyzes the
      oxidation of polyunsaturated fatty acids, generating an assortment of
      biologically relevant signaling mediators. Plant and animal lipoxygenases also
      contain a 100-150-amino acid N-terminal C2-like domain that has been implicated
      in interactions with isolated fatty acids and at the phospholipid bilayer. These
      interactions may lead to increased substrate availability and contribute to the
      regulation of active-site catalysis. Because of a lack of structural information,
      a molecular understanding of this lipid-protein interaction remains unresolved.
      Herein, we employed hydrogen-deuterium exchange MS (HDXMS) to spatially resolve
      changes in protein conformation upon interaction of soybean lipoxygenase with a
      fatty acid surrogate, oleyl sulfate (OS), previously shown to act at a site
      separate from the substrate-binding site. Specific, OS-induced conformational
      changes are detected both at the N-terminal domain and within the substrate
      portal nearly 30 A away. Combining previously measured kinetic properties in the
      presence of OS with its impact on the Kd for linoleic acid substrate binding, we
      conclude that OS binding brings about an increase in rate constants for both the
      ingress and egress of substrate. We discuss the role of OS-induced changes in
      protein flexibility in the context of changes in the mechanism of substrate
      acquisition.

PMID- 29191829
TI  - ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal
      adenocarcinoma by abrogating gemcitabine-mediated DNA damage.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor
      prognosis. Gemcitabine, as a single agent or in combination therapy, remains the
      frontline chemotherapy despite its limited efficacy due to de novo or acquired
      chemoresistance. There is an acute need to decipher mechanisms underlying
      chemoresistance and identify new targets to improve patient outcomes. Here, we
      report a novel role for the ST6Gal-I sialyltransferase in gemcitabine resistance.
      Utilizing MiaPaCa-2 and BxPC-3 PDAC cells, we found that knockdown (KD) of ST6Gal
      I expression, as well as removal of surface alpha2-6 sialic acids by
      neuraminidase, enhances gemcitabine-mediated cell death assessed via clonogenic
      assays and cleaved caspase 3 expression. Additionally, KD of ST6Gal-I potentiates
      gemcitabine-induced DNA damage as measured by comet assays and quantification of
      gammaH2AX foci. ST6Gal-I KD also alters mRNA expression of key gemcitabine
      metabolic genes, RRM1, RRM2, hENT1, and DCK, leading to an increased gemcitabine
      sensitivity ratio, an indicator of gemcitabine toxicity. Gemcitabine-resistant
      MiaPaCa-2 cells display higher ST6Gal-I levels than treatment-naive cells along
      with a reduced gemcitabine sensitivity ratio, suggesting that chronic
      chemotherapy selects for clonal variants with more abundant ST6Gal-I. Finally, we
      examined Suit2 PDAC cells and Suit2 derivatives with enhanced metastatic
      potential. Intriguingly, three metastatic and chemoresistant subclones, S2-CP9,
      S2-LM7AA, and S2-013, exhibit up-regulated ST6Gal-I relative to parental Suit2
      cells. ST6Gal-I KD in S2-013 cells increases gemcitabine-mediated DNA damage,
      indicating that suppressing ST6Gal-I activity sensitizes inherently resistant
      cells to gemcitabine. Together, these findings place ST6Gal-I as a critical
      player in imparting gemcitabine resistance and as a potential target to restore
      PDAC chemoresponse.

PMID- 29191830
TI  - Lipoic acid metabolism and mitochondrial redox regulation.
AB  - Lipoic acid is an essential cofactor for mitochondrial metabolism and is
      synthesized de novo using intermediates from mitochondrial fatty-acid synthesis
      type II, S-adenosylmethionine and iron-sulfur clusters. This cofactor is required
      for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes,
      including pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched
      chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in
      stabilizing and regulating these multienzyme complexes. Many of these
      dehydrogenases are regulated by reactive oxygen species, mediated through the
      disulfide bond of the prosthetic lipoyl moiety. Collectively, its functions
      explain why lipoic acid is required for cell growth, mitochondrial activity, and
      coordination of fuel metabolism.

PMID- 29191831
TI  - Structural features of alpha-synuclein amyloid fibrils revealed by Raman
      spectroscopy.
AB  - Parkinson's disease (PD) is associated with the formation of alpha-synuclein
      amyloid fibrils. Elucidating the role of these beta-sheet-rich fibrils in disease
      progression is crucial; however, collecting detailed structural information on
      amyloids is inherently difficult because of their insoluble, non-crystalline, and
      polymorphic nature. Here, we show that Raman spectroscopy is a facile technique
      for characterizing structural features of alpha-synuclein fibrils. Combining
      Raman spectroscopy with aggregation kinetics and transmission electron
      microscopy, we examined the effects of pH and ionic strength as well as four PD
      related mutations (A30P, E46K, G51D, and A53T) on alpha-synuclein fibrils. Raman
      spectral differences were observed in the amide-I, amide-III, and fingerprint
      regions, indicating that secondary structure and tertiary contacts are influenced
      by pH and to a lesser extent by NaCl. Faster aggregation times appear to
      facilitate unique fibril structure as determined by the highly reproducible amide
      I band widths, linking aggregation propensity and fibril polymorphism.
      Importantly, Raman spectroscopy revealed molecular-level perturbations of fibril
      conformation by the PD-related mutations that are not apparent through
      transmission electron microscopy or limited proteolysis. The amide-III band was
      found to be particularly sensitive, with G51D exhibiting the most distinctive
      features, followed by A53T and E46K. Relating to a cellular environment, our data
      would suggest that fibril polymorphs can be formed in different cellular
      compartments and potentially result in distinct phenotypes. Our work sets a
      foundation toward future cellular Raman studies of amyloids.

PMID- 29191832
TI  - Molecular characterization of human anti-hinge antibodies derived from single
      cell cloning of normal human B cells.
AB  - Anti-hinge antibodies (AHAs) are an autoantibody subclass that, following
      proteolytic cleavage, recognize cryptic epitopes exposed in the hinge regions of
      immunoglobulins (Igs) and do not bind to the intact Ig counterpart. AHAs have
      been postulated to exacerbate chronic inflammatory disorders such as inflammatory
      bowel disease and rheumatoid arthritis. On the other hand, AHAs may protect
      against invasive microbial pathogens and cancer. However, despite more than 50
      years of study, the origin and specific B cell compartments that express AHAs
      remain elusive. Recent research on serum AHAs suggests that they arise during an
      active immune response, in contrast to previous proposals that they derive from
      the preexisting immune repertoire in the absence of antigenic stimuli. We report
      here the isolation and characterization of AHAs from memory B cells, although
      anti-hinge-reactive B cells were also detected in the naive B cell compartment.
      IgG AHAs cloned from a single human donor exhibited restricted specificity for
      protease-cleaved F(ab')2 fragments and did not bind the intact IgG counterpart.
      The cloned IgG-specific AHA-variable regions were mutated from germ line-derived
      sequences and displayed a high sequence variability, confirming that these AHAs
      underwent class-switch recombination and somatic hypermutation. Consistent with
      previous studies of serum AHAs, several of these clones recognized a linear,
      peptide-like epitope, but one clone was unique in recognizing a conformational
      epitope. All cloned AHAs could restore immune effector functions to
      proteolytically generated F(ab')2 fragments. Our results confirm that a diverse
      set of epitope-specific AHAs can be isolated from a single human donor.

PMID- 29191833
TI  - Autophagy and disease.
AB  - As outlined in the accompanying Minireviews, autophagy is a complicated and
      highly regulated process that delivers cellular material to lysosomes for
      degrading, recycling, and generating molecules that fuel cellular metabolism.
      Autophagy is important for normal cellular and organismal physiology, and both
      increased and decreased autophagy has been associated with disease. Importantly,
      these connections are already being exploited to treat patients with dozens of
      clinical trials that aim to manipulate autophagy to treat (or prevent) disease.
      This Minireview discusses some of the important issues and problems to be solved
      if these efforts are to be successful.

PMID- 29191834
TI  - Three mammalian tropomyosin isoforms have different regulatory effects on
      nonmuscle myosin-2B and filamentous beta-actin in vitro.
AB  - The metazoan actin cytoskeleton supports a wide range of contractile and
      transport processes. Recent studies have shown how the dynamic association with
      specific tropomyosin isoforms generates actin filament populations with distinct
      functional properties. However, critical details of the associated molecular
      interactions remain unclear. Here, we report the properties of actomyosin
      tropomyosin complexes containing filamentous beta-actin, nonmuscle myosin-2B (NM
      2B) constructs, and either tropomyosin isoform Tpm1.8cy (b.-.b.d), Tpm1.12br (b.
      .b.c), or Tpm3.1cy (b.-.a.d). Our results show the extent to which the
      association of filamentous beta-actin with these different tropomyosin
      cofilaments affects the actin-mediated activation of NM-2B and the release of the
      ATP hydrolysis products ADP and phosphate from the active site. Phosphate release
      gates a transition from weak to strong F-actin-binding states. The release of ADP
      has the opposite effect. These changes in dominant rate-limiting steps have a
      direct effect on the duty ratio, the fraction of time that NM-2B spends in
      strongly F-actin-bound states during ATP turnover. The duty ratio is increased ~3
      fold in the presence of Tpm1.12 and 5-fold for both Tpm1.8 and Tpm3.1. The
      presence of Tpm1.12 extends the time required per ATP hydrolysis cycle 3.7-fold,
      whereas it is shortened by 27 and 63% in the presence of Tpm1.8 and Tpm3.1,
      respectively. The resulting Tpm isoform-specific changes in the frequency,
      duration, and efficiency of actomyosin interactions establish a molecular basis
      for the ability of these complexes to support cellular processes with widely
      divergent demands in regard to force production, capacity to move processively,
      and speed of movement.

PMID- 29191835
TI  - Phosphorylation of human enhancer filamentation 1 (HEF1) stimulates interaction
      with Polo-like kinase 1 leading to HEF1 localization to focal adhesions.
AB  - Elevated expression of human enhancer filamentation 1 (HEF1; also known as NEDD9
      or Cas-L) is an essential stimulus for the metastatic process of various solid
      tumors. This process requires HEF1 localization to focal adhesions (FAs).
      Although the association of HEF1 with FAs is considered to play a role in cancer
      cell migration, the mechanism targeting HEF1 to FAs remains unclear. Moreover, up
      regulation of Polo-like kinase 1 (Plk1) positively correlates with human cancer
      metastasis, yet how Plk1 deregulation promotes metastasis remains elusive. Here,
      we report that casein kinase 1delta (CK1delta) phosphorylates HEF1 at Ser-780 and
      Thr-804 and that these phosphorylation events promote a physical interaction
      between Plk1 and HEF1. We found that this interaction is critical for HEF1
      translocation to FAs and for inducing migration of HeLa cells. Plk1-docking
      phosphoepitopes were mapped/confirmed in HEF1 by various methods, including X-ray
      crystallography, and mutated for functional analysis in HeLa cells. In summary,
      our results reveal the role of a phosphorylation-dependent HEF1-Plk1 complex in
      HEF1 translocation to FAs to induce cell migration. Our findings provide critical
      mechanistic insights into the HEF1-Plk1 complex-dependent localization of HEF1 to
      FAs underlying the metastatic process and may therefore contribute to the
      development of new cancer therapies.

PMID- 29191836
TI  - Steady-state analysis of enzymes with non-Michaelis-Menten kinetics: The
      transport mechanism of Na+/K+-ATPase.
AB  - Procedures to define kinetic mechanisms from catalytic activity measurements that
      obey the Michaelis-Menten equation are well established. In contrast, analytical
      tools for enzymes displaying non-Michaelis-Menten kinetics are underdeveloped,
      and transient-state measurements, when feasible, are therefore preferred in
      kinetic studies. Of note, transient-state determinations evaluate only partial
      reactions, and these might not participate in the reaction cycle. Here, we
      provide a general procedure to characterize kinetic mechanisms from steady-state
      determinations. We described non-Michaelis-Menten kinetics with equations
      containing parameters equivalent to kcat and Km and modeled the underlying
      mechanism by an approach similar to that used under Michaelis-Menten kinetics.
      The procedure enabled us to evaluate whether Na+/K+-ATPase uses the same sites to
      alternatively transport Na+ and K+ This ping-pong mechanism is supported by
      transient-state studies but contradicted to date by steady-state analyses
      claiming that the release of one cationic species as product requires the binding
      of the other (ternary-complex mechanism). To derive robust conclusions about the
      Na+/K+-ATPase transport mechanism, we did not rely on ATPase activity
      measurements alone. During the catalytic cycle, the transported cations become
      transitorily occluded (i.e. trapped within the enzyme). We employed radioactive
      isotopes to quantify occluded cations under steady-state conditions. We replaced
      K+ with Rb+ because 42K+ has a short half-life, and previous studies showed that
      K+- and Rb+-occluded reaction intermediates are similar. We derived conclusions
      regarding the rate of Rb+ deocclusion that were verified by direct measurements.
      Our results validated the ping-pong mechanism and proved that Rb+ deocclusion is
      accelerated when Na+ binds to an allosteric, nonspecific site, leading to a 2
      fold increase in ATPase activity.

PMID- 29191838
TI  - Call for increased pharmacovigilance of gabapentin.

PMID- 29191839
TI  - Shortened telomeres in essential thrombocythemia: clinicopathological and
      treatment correlations.

PMID- 29191840
TI  - Macrocytosis and dysplastic anemia is associated with the cyclin-dependent kinase
      4/6 inhibitor palbociclib in metastatic breast cancer.

PMID- 29191837
TI  - Age-dependent increase in angiopoietin-like protein 2 accelerates skeletal muscle
      loss in mice.
AB  - Skeletal muscle atrophy, or sarcopenia, is commonly observed in older individuals
      and in those with chronic disease and is associated with decreased quality of
      life. There is recent medical and broad concern that sarcopenia is rapidly
      increasing worldwide as populations age. At present, strength training is the
      only effective intervention for preventing sarcopenia development, but it is not
      known how this exercise regimen counteracts this condition. Here, we report that
      expression of the inflammatory mediator angiopoietin-like protein 2 (ANGPTL2)
      increases in skeletal muscle of aging mice. Moreover, in addition to exhibiting
      increased inflammation and accumulation of reactive oxygen species (ROS),
      denervated atrophic skeletal muscles in a mouse model of denervation-induced
      muscle atrophy had increased ANGPTL2 expression. Interestingly, mice with a
      skeletal myocyte-specific Angptl2 knockout had attenuated inflammation and ROS
      accumulation in denervated skeletal muscle, accompanied by increased satellite
      cell activity and inhibition of muscular atrophy compared with mice harboring
      wildtype Angptl2 Moreover, consistent with these phenotypes, wildtype mice
      undergoing exercise training displayed decreased ANGPTL2 expression in skeletal
      muscle. In conclusion, ANGPTL2 up-regulation in skeletal myocytes accelerates
      muscle atrophy, and exercise-induced attenuation of ANGPTL2 expression in those
      tissues may partially explain how exercise training prevents sarcopenia.

PMID- 29191841
TI  - PIEZO1-R1864H rare variant accounts for a genetic phenotype-modifier role in
      dehydrated hereditary stomatocytosis.

PMID- 29191843
TI  - Expression of programmed death-1 on lymphocytes in myeloma patients is lowered
      during lenalidomide maintenance.

PMID- 29191842
TI  - Targeting the anion exchanger 2 with specific peptides as a new therapeutic
      approach in B lymphoid neoplasms.
AB  - Regulatory T (Treg) cells can weaken antitumor immune responses, and inhibition
      of their function appears to be a promising therapeutic approach in cancer
      patients. Mice with targeted deletion of the gene encoding the Cl-/HCO3- anion
      exchanger AE2 (also termed SLC4A2), a membrane-bound carrier involved in
      intracellular pH regulation, showed a progressive decrease in the number of Treg
      cells. We therefore challenged AE2 as a potential target for tumor therapy, and
      generated linear peptides designed to bind the third extracellular loop of AE2,
      which is crucial for its exchange activity. Peptide p17AE2 exhibited optimal
      interaction ability and indeed promoted apoptosis in mouse and human Treg cells,
      while activating effector T-cell function. Interestingly, this linear peptide
      also induced apoptosis in different types of human leukemia, lymphoma and
      multiple myeloma cell lines and primary malignant samples, while it showed only
      moderate effects on normal B lymphocytes. Finally, a macrocyclic AE2 targeting
      peptide exhibiting increased stability in vivo was effective in mice xenografted
      with B-cell lymphoma. These data suggest that targeting the anion exchanger AE2
      with specific peptides may represent an effective therapeutic approach in B-cell
      malignancies.

PMID- 29191844
TI  - Reduction in Hypoglycemia With the Predictive Low-Glucose Management System: A
      Long-term Randomized Controlled Trial in Adolescents With Type 1 Diabetes.
AB  - OBJECTIVE: Short-term studies with automated systems that suspend basal insulin
      when hypoglycemia is predicted have shown a reduction in hypoglycemia; however,
      efficacy and safety have not been established in long-term trials. RESEARCH
      DESIGN AND METHODS: We conducted a 6-month, multicenter, randomized controlled
      trial in children and adolescents with type 1 diabetes using the Medtronic
      MiniMed 640G pump with Suspend before low (predictive low-glucose management
      [PLGM]) compared with sensor-augmented pump therapy (SAPT) alone. The primary
      outcome was percentage time in hypoglycemia with sensor glucose (SG) <3.5 mmol/L
      (63 mg/dL). RESULTS: In an intent-to-treat analysis of 154 subjects, 74 subjects
      were randomized to SAPT and 80 subjects to PLGM. At baseline, the time with SG
      <3.5 mmol/L was 3.0% and 2.8% in the SAPT and PLGM groups, respectively. During
      the study, PLGM was associated with a reduction in hypoglycemia compared with
      SAPT (% time SG <3.5 mmol/L: SAPT vs. PLGM, 2.6 vs. 1.5, P < 0.0001). A similar
      effect was also noted in time with SG <3 mmol/L (P < 0.0001). This reduction was
      seen both during day and night (P < 0.0001). Hypoglycemic events (SG <3.5 mmol/L
      for >20 min) also declined with PLGM (SAPT vs. PLGM: events/patient-year 227 vs.
      139, P < 0.001). There was no difference in glycated hemoglobin (HbA1c) at 6
      months (SAPT 7.6 +/- 1.0% vs. PLGM 7.8 +/- 0.8%, P = 0.35). No change in quality
      of life measures was reported by participants/parents in either group. There were
      no PLGM-related serious adverse events. CONCLUSIONS: In children and adolescents
      with type 1 diabetes, PLGM reduced hypoglycemia without deterioration in glycemic
      control.

PMID- 29191846
TI  - Acquired triggering of the fingers and thumb in adults.

PMID- 29191845
TI  - Revisiting the Relationships Between Measures of Glycemic Control and
      Hypoglycemia in Continuous Glucose Monitoring Data Sets.
AB  - OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) identified an
      inverse relationship between HbA1c and severe hypoglycemia. We investigated the
      relationship between hypoglycemia and HbA1c in a large type 1 diabetes cohort on
      multiple daily injection or insulin pump therapy using blinded continuous glucose
      monitoring (CGM) data. The impact of real-time CGM on these relationships and how
      these relationships differ with biochemical definitions of hypoglycemia have also
      been assessed. RESEARCH DESIGN AND METHODS: CGM data were obtained from the JDRF
      CGM randomized control trial. Baseline blinded CGM data were used to assess time
      in hypoglycemia in all individuals. End point data from the CGM intervention
      group were used to assess the impact of CGM. Percentage of time spent below 3.9,
      3.3, 3.0, and 2.8 mmol/L were calculated and quadratic regression plots drawn.
      Relationships were analyzed visually, and ANOVA was used to assess relationships
      between glycemia and time below threshold. RESULTS: J-shaped relationships were
      observed for all biochemical hypoglycemia thresholds, with the lowest
      hypoglycemia risk occurring at HbA1c values between 8.1 and 8.6% (65-70
      mmol/mol). The use of an average of 5 days/week of CGM flattened the
      relationships for 3.3, 3.0, and 2.8 mmol/L, and ANOVA confirmed the loss of
      relationship for the 3.3 mmol/L threshold using CGM. CONCLUSIONS: The
      relationship between hypoglycemia and HbA1c in a population with type 1 diabetes
      is J-shaped. Lower HbA1c values are still associated with increased hypoglycemia
      risk, although the magnitude of risk depends on biochemical threshold. Real-time
      CGM may reduce the percentage time spent in hypoglycemia, changing the
      relationship between HbA1c and hypoglycemia.

PMID- 29191847
TI  - WASP family proteins and formins compete in pseudopod- and bleb-based migration.
AB  - Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in
      eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven
      forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum,
      loss of SCAR is compensated by WASP moving to the leading edge to generate
      morphologically normal pseudopods. Here we use an inducible double knockout to
      show that cells lacking both SCAR and WASP are unable to grow, make pseudopods
      or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin
      polymerization are normal. Pseudopods are replaced in double SCAR/WASP mutants by
      aberrant filopods, induced by the formin dDia2. Further disruption of the gene
      for dDia2 restores cells' ability to initiate blebs and thus migrate, though
      pseudopods are still lost. Triple knockout cells still contain near-normal F
      actin levels. This work shows that SCAR, WASP, and dDia2 compete for actin. Loss
      of SCAR and WASP causes excessive dDia2 activity, maintaining F-actin levels but
      blocking pseudopod and bleb formation and migration.

PMID- 29191849
TI  - Statin Treatment in Patients With Intracerebral Hemorrhage.

PMID- 29191848
TI  - Keratin 6a reorganization for ubiquitin-proteasomal processing is a direct
      antimicrobial response.
AB  - Skin and mucosal epithelia deploy antimicrobial peptides (AMPs) to eliminate
      harmful microbes. We reported that the intermediate filament keratin 6a (K6a) is
      constitutively processed into antimicrobial fragments in corneal epithelial
      cells. In this study, we show that K6a network remodeling is a host defense
      response that directly up-regulates production of keratin-derived AMPs (KAMPs) by
      the ubiquitin-proteasome system (UPS). Bacterial ligands trigger K6a
      phosphorylation at S19, S22, S37, and S60, leading to network disassembly.
      Mutagenic analysis of K6a confirmed that the site-specific phosphorylation
      augmented its solubility. K6a in the cytosol is ubiquitinated by cullin-RING E3
      ligases for subsequent proteasomal processing. Without an appreciable increase in
      K6a gene expression and proteasome activity, a higher level of cytosolic K6a
      results in enhanced KAMP production. Although proteasome-mediated proteolysis is
      known to produce antigenic peptides in adaptive immunity, our findings
      demonstrate its new role in producing AMPs for innate immune defense.
      Manipulating K6a phosphorylation or UPS activity may provide opportunities to
      harness the innate immunity of epithelia against infection.

PMID- 29191850
TI  - Long-Term Effect of Pravastatin on Carotid Intima-Media Complex Thickness: The J
      STARS Echo Study (Japan Statin Treatment Against Recurrent Stroke).
AB  - BACKGROUND AND PURPOSE: The effect of statins on progression of carotid intima
      media complex thickness (IMT) has been shown exclusively in nonstroke Western
      patients. This study aimed to determine the effect of low-dose pravastatin on
      carotid IMT in Japanese patients with noncardioembolic ischemic stroke. METHODS:
      This is a substudy of the J-STARS trial (Japan Statin Treatment Against Recurrent
      Stroke), a multicenter, randomized, open-label, parallel-group trial to examine
      whether pravastatin reduces stroke recurrence. Patients were randomized to
      receive pravastatin (10 mg daily, usual dose in Japan; pravastatin group) or not
      to receive any statins (control group). The primary outcome was IMT change of the
      common carotid artery for a 5-year observation period. IMT change was compared
      using mixed-effects models for repeated measures. RESULTS: Of 864 patients
      registered in this substudy, 71 without baseline ultrasonography were excluded,
      and 388 were randomly assigned to the pravastatin group and 405 to the control
      group. Baseline characteristics were not significantly different, except National
      Institutes of Health Stroke Scale scores (median, 0 [interquartile range, 0-2]
      versus 1 [interquartile range, 0-2]; P=0.019) between the 2 groups. Baseline IMT
      (mean+/-SD) was 0.887+/-0.155 mm in the pravastatin group and 0.887+/-0.152 mm in
      the control group (P=0.99). The annual change in the IMT at 5-year visit was
      significantly reduced in the pravastatin group as compared with that in the
      control group (0.021+/-0.116 versus 0.040+/-0.118 mm; P=0.010). CONCLUSIONS: The
      usual Japanese dose of pravastatin significantly reduced the progression of
      carotid IMT at 5 years in patients with noncardioembolic stroke. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00361530.

PMID- 29191853
TI  - A non-cardiac cause of bilateral leg swelling.

PMID- 29191851
TI  - DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed
      Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging-Fluid Attenuated
      Inversion Recovery) Mismatch in Thrombectomy Candidates: An Intrarater and
      Interrater Agreement Study.
AB  - BACKGROUND AND PURPOSE: We aimed to study the intrarater and interrater agreement
      of clinicians attributing DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke
      Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted
      Imaging-Fluid Attenuated Inversion Recovery) mismatch in patients with acute
      ischemic stroke referred for mechanical thrombectomy. METHODS: Eighteen raters
      independently scored anonymized magnetic resonance imaging scans of 30
      participants from a multicentre thrombectomy trial, in 2 different reading
      sessions. Agreement was measured using Fleiss kappa and Cohen kappa statistics.
      RESULTS: Interrater agreement for DWI-ASPECTS was slight (kappa=0.17 [0.14
      0.21]). Four raters (22.2%) had a substantial (or higher) intrarater agreement.
      Dichotomization of the DWI-ASPECTS (0-5 versus 6-10 or 0-6 versus 7-10) increased
      the interrater agreement to a substantial level (kappa=0.62 [0.48-0.75] and 0.68
      [0.55-0.79], respectively) and more raters reached a substantial (or higher)
      intrarater agreement (17/18 raters [94.4%]). Interrater agreement for DWI-FLAIR
      mismatch was moderate (kappa=0.43 [0.33-0.57]); 11 raters (61.1%) reached a
      substantial (or higher) intrarater agreement. CONCLUSIONS: Agreement between
      clinicians assessing DWI-ASPECTS and DWI-FLAIR mismatch may not be sufficient to
      make repeatable clinical decisions in mechanical thrombectomy. The
      dichotomization of the DWI-ASPECTS (0-5 versus 0-6 or 0-6 versus 7-10) improved
      interrater and intrarater agreement, however, its relevance for patients
      selection for mechanical thrombectomy needs to be validated in a randomized
      trial.

PMID- 29191852
TI  - Challenge and Yield of Enrolling Racially and Ethnically Diverse Patient
      Populations in Low Event Rate Clinical Trials.
AB  - BACKGROUND AND PURPOSE: We report patient enrollment and retention by race and
      ethnicity in the CREST (Carotid Revascularization Endarterectomy Versus Stent
      Trial) and assess potential effect modification by race/ethnicity. In addition,
      we discuss the challenge of detecting differences in study outcomes when
      subgroups are small and the event rate is low. METHODS: We compared 2502 patients
      by race, ethnicity, baseline characteristics, and primary outcome (any
      periprocedural stroke, death, or myocardial infarction and subsequent ipsilateral
      stroke up to 10 years). RESULTS: Two hundred forty (9.7%) patients were minority
      by race (6.1%) or ethnicity (3.6%); 109 patients (4.4%) were black, 32 (1.3%)
      Asian, 2332 (93.4%) white, 11 (0.4%) other, and 18 (0.7%) unknown. Ninety (3.6%)
      were Hispanic, 2377 (95%) non-Hispanic, and 35 (1.4%) unknown. The rate of the
      primary end point for all patients was 10.9%+/-0.9% at 10 years and did not
      differ by race or ethnicity (Pinter>0.24). CONCLUSIONS: The proportion of
      minorities recruited to CREST was below their representation in the general
      population, and retention of minority patients was lower than for whites. Primary
      outcomes did not differ by race or ethnicity. However, in CREST (like other
      studies), the lack of evidence of a racial/ethnic difference in the treatment
      effect should be interpreted with caution because of low statistical power to
      detect such a difference. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

PMID- 29191854
TI  - Intended Versus Inferred Treatment After 18F-Fluoride PET Performed for
      Evaluation of Osseous Metastatic Disease in the National Oncologic PET Registry.
AB  - We have previously reported that PET with 18F-fluoride (NaF PET) for assessment
      of osseous metastatic disease led to changes in intended management in a
      substantial fraction of patients with prostate or other types of cancer
      participating in the National Oncologic PET Registry. This study was performed to
      assess the concordance of intended patient management after NaF PET and inferred
      management based on analysis of Medicare claims. Methods: We analyzed linked post
      NaF PET data of consenting National Oncologic PET Registry participants age 65 y
      or older from 2011 to 2014 and their corresponding Medicare claims. Post-NaF PET
      treatment plans, including combinations of 2 modes of therapy, were assessed for
      their concordance with clinical actions inferred from Medicare claims. NaF PET
      studies were stratified by indication (initial staging [IS] or suspected first
      osseous metastasis [FOM]) and cancer type (prostate, lung, or other cancers).
      Agreement was assessed between post-NaF PET intended management plans for
      treatment (surgery, radiotherapy, or systemic therapy) within 90 d for lung and
      180 d for prostate or other cancers, and for watching (the absence of treatment
      claims for >=60 d) as compared with claims-inferred care. Results: Actions after
      9,898 scans were assessed. After NaF PET for IS, there was claims agreement for
      planned surgery in 76.0% (19/25) lung, 75.4% (98/130) other cancers, and 58.9%
      (298/506) prostate cancer. Claims confirmed chemotherapy plans after NaF PET done
      for IS or FOM in 81.0% and 73.5% for lung cancer (n = 148 and 136) and 69.4% and
      67.5% for other cancers (n = 111 and 228). For radiotherapy plans, agreement
      ranged from 80.0% to 84.4% after IS and 68.4% to 74.0% for suspected FOM.
      Concordance was greatest for androgen deprivation therapy (ADT) (86.0%, n = 308)
      alone or combined with radiotherapy in prostate cancer IS (80.8%, n = 517). In
      prostate FOM, the concordance across all treatment plans was lower if the
      patients had ADT claims within 180 d before NaF PET. Agreement with nontreatment
      plans was high for FOM (87.2% in other cancers and 78.6% if no prior ADT in
      prostate) and low after IS (40.7%-62.5%). Conclusion: Concordance of post-NaF PET
      plans and claims was substantial and higher overall for IS than for FOM.

PMID- 29191855
TI  - Sensitivity Comparison of 68Ga-OPS202 and 68Ga-DOTATOC PET/CT in Patients with
      Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase II Imaging
      Study.
AB  - Radiolabeled somatostatin (sst) receptor agonists are integral to the diagnosis
      of gastroenteropancreatic neuroendocrine tumors (NETs), but detection rates,
      especially of liver metastases, remain limited even with PET/CT. 68Ga-OPS202
      (68Ga-NODAGA-JR11; NODAGA = 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic
      acid and JR11 = Cpa-c(dCys-Aph(Hor)-dAph(Cbm)-Lys-Thr-Cys)-dTyr-NH2)), a novel
      radiolabeled sst receptor antagonist with a high affinity for the sst2 receptor,
      has the potential to perform better than sst receptor agonists. Here, we present
      the results of the phase II component of a phase I/II study that evaluated the
      sensitivity of 68Ga-OPS202, compared with the reference compound, 68Ga-DOTATOC
      (an sst receptor agonist), in PET imaging. Methods: Patients received a single
      150-MBq intravenous injection of 68Ga-DOTATOC (15 MUg of peptide) and 2 single
      150-MBq intravenous injections of 68Ga-OPS202 (15 MUg of peptide at visit 1 and
      50 MUg at visit 2). Whole-body PET/CT acquisitions were performed 1 h after
      injection on the same calibrated PET/CT scanner. Diagnostic efficacy measures
      were compared against contrast medium-enhanced CT or MRI as the gold standard.
      Two independent masked experts read the scans, and both outcomes were combined
      for analysis. Results: Twelve consecutive patients with low- or intermediate
      grade gastroenteropancreatic NETs took part in this prospective study. Image
      contrast for matched malignant liver lesions was significantly higher for the
      68Ga-OPS202 scans than for the 68Ga-DOTATOC scan: the median of the mean tumor-to
      background SUVmax ratios were significantly higher for 15 and 50 MUg of 68Ga
      OPS202 (5.3 and 4.3, with interquartile ranges of 2.9-5.7 and 3.4-6.3 and P
      values of 0.004 and 0.008) than for 68Ga-DOTATOC (1.9, with an interquartile
      range of 1.4-2.9). The higher tumor-to-background ratio of 68Ga-OPS202 resulted
      not only in a higher detection rate of liver metastases but also in a
      significantly higher lesion-based overall sensitivity with the antagonist than
      with 68Ga-DOTATOC: 94% and 88% for 50 and 15 MUg of 68Ga-OPS202, respectively,
      and 59% for 15 MUg of 68Ga-DOTATOC (P < 0.001). Positive predictive values for
      68Ga-OPS202 PET/CT and 68Ga-DOTATOC PET/CT were similar (~98%). There were no
      significant differences in image contrast, sensitivity, or positive predictive
      values between the 2 68Ga-OPS202 peptide doses, indicating a high
      reproducibility. Conclusion: Preliminary diagnostic efficacy data from this phase
      II study indicate that 68Ga-OPS202 has high sensitivity for the detection of
      gastroenteropancreatic NETs. Further studies in larger patient populations are
      warranted.

PMID- 29191856
TI  - PSMA-11-Derived Dual-Labeled PSMA Inhibitors for Preoperative PET Imaging and
      Precise Fluorescence-Guided Surgery of Prostate Cancer.
AB  - Resection of tumors using targeted dual-modality probes combining preoperative
      imaging with intraoperative guidance is of high clinical relevance and might
      considerably affect the outcome of prostate cancer therapy. This work aimed at
      the development of dual-labeled prostate-specific membrane antigen (PSMA)
      inhibitors derived from the established N,N'-bis[2-hydroxy-5
      (carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC)-based PET
      tracer 68Ga-Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) to allow accurate
      intraoperative detection of PSMA-positive tumors. Methods: A series of novel PSMA
      targeting fluorescent dye conjugates of Glu-urea-Lys-HBED-CC was synthesized, and
      their biologic properties were determined in cell-based assays and confocal
      microscopy. As a preclinical proof of concept, specific tumor uptake,
      pharmacokinetics, and feasibility for intraoperative fluorescence guidance were
      investigated in tumor-bearing mice and healthy pigs. Results: The designed dual
      labeled PSMA inhibitors exhibited high binding affinity and PSMA-specific
      effective internalization. Conjugation of fluorescein isothiocyanate (10.86 +/-
      0.94 percentage injected dose [%ID]/g), IRDye800CW (13.66 +/- 3.73 %ID/g), and
      DyLight800 (15.62 +/- 5.52 %ID/g) resulted in a significantly increased specific
      tumor uptake, whereas 68Ga-Glu-urea-Lys-HBED-CC-AlexaFluor488 (9.12 +/- 5.47
      %ID/g) revealed a tumor uptake similar to that of 68Ga-PSMA-11 (4.89 +/- 1.34
      %ID/g). The first proof-of-concept studies with the clinically relevant candidate
      68Ga-Glu-urea-Lys-HBED-CC-IRDye800CW reinforced a fast, specific enrichment in
      PSMA-positive tumors, with rapid background clearance. With regard to
      intraoperative navigation, a specific fluorescence signal was detected in PSMA
      expressing tissue. Conclusion: This study demonstrated that PSMA-11-derived dual
      labeled dye conjugates are feasible for providing PSMA-specific pre-, intra-, and
      postoperative detection of prostate cancer lesions and have high potential for
      future clinical translation.

PMID- 29191857
TI  - Evaluation of 11C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B
      Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk.
AB  - Clinical and preclinical research with modulators at the N-methyl-d-aspartate
      (NMDA) receptor GluN2B N-terminal domain (NTD) aims for the treatment of various
      neurologic diseases. The interpretation of the results is hampered by the lack of
      a suitable NMDA PET tracer for assessing the receptor occupancy of potential
      drugs. We have developed 11C-Me-NB1 as a PET tracer for imaging GluN1/GluN2B
      containing NMDA receptors and used it to investigate in rats the dose-dependent
      receptor occupancy of eliprodil, a GluN2B NTD modulator. Methods:11C-Me-NB1 was
      synthesized and characterized by in vitro displacement binding experiments with
      rat brain membranes, in vitro autoradiography, and blocking and displacement
      experiments by PET and PET kinetic modeling. Receptor occupancy by eliprodil was
      studied by PET with 11C-Me-NB1. Results:11C-Me-NB1 was synthesized at 290 +/- 90
      GBq/MUmol molar activity, 7.4 +/- 1.9 GBq total activity at the end of synthesis
      (n = 17), and more than 99% radiochemical purity. 11C-Me-NB1 binding in rat brain
      was blocked in vitro and in vivo by the NTD modulators Ro-25-6981 and eliprodil.
      Half-maximal receptor occupancy by eliprodil occurred at 1.5 MUg/kg. At 1 mg/kg
      of eliprodil, a dose with reported neuroprotective effects, more than 99.5% of
      binding sites were occupied. In vitro, 11C-Me-NB1 binding was independent of the
      sigma-1 receptor (Sigma1R), and the Sigma1R agonist (+)-pentazocine did not
      compete for high-affinity binding. In vivo, a 2.5 mg/kg dose of (+)-pentazocine
      abolished 11C-Me-NB1-specific binding, indicating an indirect effect of Sigma1R
      on 11C-Me-NB1 binding. Conclusion:11C-Me-NB1 is suitable for the in vivo imaging
      of NMDA GluN1/GluN2B receptors and the assessment of receptor occupancy by NTD
      modulators. GluN1/GluN2B NMDA receptors are fully occupied at neuroprotective
      doses of eliprodil. Furthermore, 11C-Me-NB1 enables imaging of GluN1/GluN2B NMDA
      receptor cross talk.

PMID- 29191858
TI  - Flortaucipir F 18 Quantitation Using Parametric Estimation of Reference Signal
      Intensity.
AB  - PET imaging of tau pathology in Alzheimer disease may benefit from the use of
      white matter reference regions. These regions have shown reduced variability
      compared with conventional cerebellar regions in amyloid imaging. However, they
      are susceptible to contamination from partial-volume blurring of tracer uptake in
      the cortex. We present a new technique, PERSI (Parametric Estimation of Reference
      Signal Intensity), for flortaucipir F 18 count normalization that leverages the
      advantages of white matter reference regions while mitigating potential partial
      volume effects. Methods: Subjects with a clinical diagnosis of Alzheimer disease,
      mild cognitive impairment, or normal cognition underwent T1-weighted MRI and
      florbetapir imaging (to determine amyloid [Abeta] status) at screening and
      flortaucipir F 18 imaging at single or multiple time points. Flortaucipir F 18
      images, acquired as 4 * 5 min frames 80 min after a 370-MBq injection, were
      motion-corrected, averaged, and transformed to Montreal Neurological Institute
      (MNI) space. The PERSI reference region was calculated for each scan by fitting a
      bimodal gaussian distribution to the voxel-intensity histogram within an atlas
      based white matter region and using the center and width of the lower-intensity
      peak to identify the voxel intensities to be included. Four conventional
      reference regions were also evaluated: whole cerebellum, cerebellar gray matter,
      atlas-based white matter, and subject-specific white matter. SUVr (standardized
      uptake value ratio) was calculated for a statistically defined neocortical volume
      of interest. Performance was evaluated with respect to test-retest variability in
      a phase 2 study of 21 subjects (5-34 d between scans). Baseline variability in
      controls (SD of SUVr and DeltaSUVr) and effect sizes for group differences (Cohen
      d; Abeta-positive impaired vs. Abeta-negative normal) were evaluated in another
      phase 2 study with cross-sectional data (n = 215) and longitudinal data (n =
      142/215; 18 +/- 2 mo between scans). Results: PERSI showed superior test-retest
      reproducibility (1.84%) and group separation ability (cross-sectional Cohen d =
      9.45; longitudinal Cohen d = 2.34) compared with other reference regions.
      Baseline SUVr variability and DeltaSUVr were minimal in Abeta control subjects
      with no specific flortaucipir F 18 uptake (SUVr, 1.0 +/- 0.04; DeltaSUVr, 0.0 +/-
      0.02). Conclusion: PERSI reduced variability while enhancing discrimination
      between diagnostic cohorts. Such improvements could lead to more accurate disease
      staging and robust measurements of changes in tau burden over time for the
      evaluation of putative therapies.

PMID- 29191859
TI  - Swim and fly: escape strategy in neustonic and planktonic copepods.
AB  - Copepods can respond to predators by powerful escape jumps that in some surface
      dwelling forms may propel the copepod out of the water. We studied the kinematics
      and energetics of submerged and out-of-water jumps of two neustonic pontellid
      copepods, Anomalocera patersoni and Pontella mediterranea, and one pelagic
      calanoid copepod, Calanus helgolandicus (euxinus). We show that jumping out of
      the water does not happen just by inertia gained during the copepod's
      acceleration underwater, but also requires the force generated by the thoracic
      limbs when breaking through the water's surface to overcome surface tension, drag
      and gravity. The timing of this appears to be necessary for success. At the
      moment of breaking the water interface, the instantaneous velocity of the two
      pontellids reached 125 cm s-1, while their maximum underwater speed (115 cm s-1)
      was close to that of similarly sized C. helgolandicus (106 cm s-1). The average
      specific power produced by the two pontellids during out-of-water jumps (1700
      3300 W kg-1 muscle mass) was close to that during submerged jumps (900-1600 W kg
      1 muscle mass) and, in turn, similar to that produced during submerged jumps of
      C. helgolandicus (1300 W kg-1 muscle mass). The pontellids may shake off water
      adhering to their body by repeated strokes of the limbs during flight, which
      leads to a slight acceleration in the air. Our observations suggest that out-of
      water jumps of pontellids are not dependent on any exceptional ability to perform
      this behavior but have the same energetic cost and are based on the same
      kinematic patterns and contractive capabilities of muscles as those of copepods
      swimming submerged.

PMID- 29191860
TI  - Hormesis-like effect of mild larval crowding on thermotolerance in Drosophila
      flies.
AB  - Crowding is a complex stress that can affect organisms' physiology, especially
      through decreased food quality and accessibility. Here, we evaluated the effect
      of larval density on several biological traits of Drosophila melanogaster An
      increasing gradient, from 1 to 1000 eggs per milliliter of food, was used to
      characterize life-history traits variations. Crowded conditions resulted in
      striking decreases of fresh mass (up to 6-fold) and viability, as well as delayed
      development. Next, we assessed heat and cold tolerance in L3 larvae reared at
      three selected larval densities: low (LD, 5 eggs ml-1), medium (MD, 60 eggs ml-1)
      and high (HD, 300 eggs ml-1). LT50 values of MD and, to a lesser extent, HD
      larvae were repeatedly higher than those from LD larvae, under both heat and cold
      stress. We investigated potential physiological correlates associated with this
      density-dependent thermotolerance shift. No marked pattern could be drawn from
      the expression of stress-related genes. However, a metabolomic analysis
      differentiated the metabotypes of the three density levels, with potential
      candidates associated with this clustering (e.g. glucose 6-phosphate, GABA,
      sugars and polyols). Under HD, signs of oxidative stress were noted but not
      confirmed at the transcriptional level. Finally, urea, a common metabolic waste,
      was found to accumulate substantially in food from MD and HD larvae. When
      supplemented in food, urea stimulated cold tolerance but reduced heat tolerance
      in LD larvae. This study highlights that larval crowding is an important
      environmental parameter that induces drastic consequences on flies' physiology
      and can affect thermotolerance in a density-specific way.

PMID- 29191861
TI  - Determining forward speed from accelerometer jiggle in aquatic environments.
AB  - How fast animals move is critical to understanding their energetic requirements,
      locomotor capacity and foraging performance, yet current methods for measuring
      speed via animal-attached devices are not universally applicable. Here, we
      present and evaluate a new method that relates forward speed to the stochastic
      motion of biologging devices as tag jiggle, the amplitude of the tag vibrations
      as measured by high sample rate accelerometers, increases exponentially with
      increasing speed. We successfully tested this method in a flow tank using two
      types of biologging devices and in situ on wild cetaceans spanning ~3 to >20 m in
      length using two types of suction cup-attached tag and two types of dart-attached
      tag. This technique provides some advantages over other approaches for
      determining speed as it is device-orientation independent and relies only on a
      pressure sensor and a high sample rate accelerometer, sensors that are nearly
      universal across biologging device types.

PMID- 29191863
TI  - Exposure to CO2 influences metabolism, calcification and gene expression of the
      thecosome pteropod Limacina retroversa.
AB  - Thecosomatous pteropods, a group of aragonite shell-bearing zooplankton, are
      becoming an important sentinel organism for understanding the influence of ocean
      acidification on pelagic organisms. These animals show vulnerability to changing
      carbonate chemistry conditions, are geographically widespread, and are both
      biogeochemically and trophically important. The objective of this study was to
      determine how increasing duration and severity of CO2 treatment influence the
      physiology of the thecosome Limacina retroversa, integrating both gene expression
      and organism-level (respiration and calcification) metrics. We exposed pteropods
      to over-saturated, near-saturated or under-saturated conditions and sampled
      individuals at 1, 3, 7, 14 and 21 days of exposure to test for the effect of
      duration. We found that calcification was affected by borderline and under
      saturated conditions by week two, while respiration appeared to be more strongly
      influenced by an interaction between severity and duration of exposure, showing
      complex changes by one week of exposure. The organismal metrics were corroborated
      by specific gene expression responses, with increased expression of
      biomineralization-associated genes in the medium and high treatments throughout
      and complex changes in metabolic genes corresponding to both captivity and CO2
      treatment. Genes associated with other physiological processes such as lipid
      metabolism, neural function and ion pumping had complex responses, influenced by
      both duration and severity. Beyond these responses, our findings detail the
      captivity effects for these pelagic organisms, providing information to
      contextualize the conclusions of previous studies, and emphasizing a need for
      better culturing protocols.

PMID- 29191862
TI  - GABAA receptors activate fish feeding behaviour via two distinct functional
      pathways.
AB  - Benzodiazepines, acting through ionotropic receptors of gamma-aminobutyric acid
      (GABAA receptors, GABAR), have been shown to modify feeding behaviour and
      increase appetite in humans and non-human subjects. However, the cellular and
      molecular mechanisms that underlie connected short-term behavioural fluctuations
      are still unclear. In the present study, we used Carassius gibelio (Prussian
      carp) as a model organism to research the impact of scantily explored
      benzodiazepine phenazepam (PNZ) on feeding behaviour and the related molecular
      mechanisms of PNZ action at single-cell and single-receptor levels. We found that
      the feeding activity of C. gibelio is under control of GABARs via two distinct
      mechanisms: orthosteric (triggered by GABA binding site) and allosteric
      (triggered by benzodiazepine binding site). PNZ displayed clear stimulatory
      effects on both mechanisms in a GABA-dependent manner. In addition, orthosteric
      and allosteric effects were found to be partially competitive, which leads to
      complex behavioural repercussions of conjoint effects of GABAR ligands.

PMID- 29191864
TI  - Ontogeny and morphometrics of the gills and swim bladder of air-breathing striped
      catfish Pangasianodon hypophthalmus.
AB  - The air-breathing fish Pangasianodon hypophthalmus has been shown to have highly
      plastic branchial surfaces whose area (SA) increases with temperature and aquatic
      hypoxia. This modulation occurs through development of inter-lamellar cell mass
      (ILCM). Paradoxically, in conditions where this fish has been shown capable of
      covering its entire aerobic scope from the water phase, it has been shown to have
      a very small branchial SA. To address this paradox, we measured the SA, harmonic
      mean diffusion distance (tauh) and calculated the anatomic diffusion factor (ADF)
      of the branchial and swim bladder surfaces in fish ranging from 3 to 1900 g at 27
      degrees C in normoxia. Since the lamellae were distinguishable from the ILCM, we
      measured the actual SA as well as the potential SA if ILCM were lost. As a result
      of low tauh, P. hypophthalmus has a high capacity for branchial oxygen uptake
      with or without ILCM. Actual and potential gill ADF were 361 and 1002 cm2 um-1 kg
      1, respectively, for a 100 g fish and the ADF of the swim bladder was found to be
      308 cm2 um-1 kg-1 By swimming fish to exhaustion at different temperatures, we
      show that modulation of this SA is rapid, indicating that the apparent paradox
      between previous studies is eliminated. Regression analysis of log-log plots of
      respiratory SA in relation to body mass shows that the gill scales with mass
      similarly to the SA in active water-breathing fish, whereas the swim bladder
      scales with mass more like the mammalian lung does. This fish presents a
      combination of respiratory surfaces not previously seen in air-breathing fish.

PMID- 29191865
TI  - Editorial: On matters of maturity, self-control, and responsiveness: inhibitory
      NK receptors in the driver's seat?

PMID- 29191866
TI  - Editorial: Stressing out mast cells via CRF1.

PMID- 29191867
TI  - Editorial: Countering immune regulation: sTim-ulating SLE disease pathogenesis.

PMID- 29191868
TI  - Alphabet Soup: Sagittal Balance Correction Osteotomies of the Spine-What
      Radiologists Should Know.
AB  - Global sagittal malalignment has been demonstrated to have correlation with
      clinical symptoms and is a key component to be restored in adult spinal
      deformity. In this article, various types of sagittal balance-correction
      osteotomies are reviewed primarily on the basis of the 3 most commonly used
      procedures: Smith-Petersen osteotomy, pedicle subtraction osteotomy, and
      vertebral column resection. Familiarity with the expected imaging appearance and
      commonly encountered complications seen on postoperative imaging studies
      following correction osteotomies is crucial for accurate image interpretation.

PMID- 29191869
TI  - John Nash and the Organization of Stroke Care.
AB  - The concept of Nash equilibrium, developed by John Forbes Nash Jr, states that an
      equilibrium in noncooperative games is reached when each player takes the best
      action for himself or herself, taking into account the actions of the other
      players. We apply this concept to the provision of endovascular thrombectomy in
      the treatment of acute ischemic stroke and suggest that collaboration among
      hospitals in a health care jurisdiction could result in practices such as shared
      call pools for neurointervention teams, leading to better patient care through
      streamlined systems.

PMID- 29191870
TI  - Reproducibility of Deep Gray Matter Atrophy Rate Measurement in a Large
      Multicenter Dataset.
AB  - BACKGROUND AND PURPOSE: Precise in vivo measurement of deep GM volume change is a
      highly demanded prerequisite for an adequate evaluation of disease progression
      and new treatments. However, quantitative data on the reproducibility of deep GM
      structure volumetry are not yet available. In this paper we aim to investigate
      this reproducibility using a large multicenter dataset. MATERIALS AND METHODS: We
      have assessed the reproducibility of 2 automated segmentation software packages
      (FreeSurfer and the FMRIB Integrated Registration and Segmentation Tool) by
      quantifying the volume changes of deep GM structures by using back-to-back MR
      imaging scans from the Alzheimer Disease Neuroimaging Initiative's multicenter
      dataset. Five hundred sixty-two subjects with scans at baseline and 1 year were
      included. Reproducibility was investigated in the bilateral caudate nucleus,
      putamen, amygdala, globus pallidus, and thalamus by carrying out descriptives as
      well as multilevel and variance component analysis. RESULTS: Median absolute back
      to-back differences varied between GM structures, ranging from 59.6-156.4 MUL for
      volume change, and 1.26%-8.63% for percentage volume change. FreeSurfer had a
      better performance for the outcome of longitudinal volume change for the
      bilateral amygdala, putamen, left caudate nucleus (P < .005), and right thalamus
      (P < .001). For longitudinal percentage volume change, Freesurfer performed
      better for the left amygdala, bilateral caudate nucleus, and left putamen (P <
      .001). Smaller limits of agreement were found for FreeSurfer for both outcomes
      for all GM structures except the globus pallidus. Our results showed that back-to
      back differences in 1-year percentage volume change were approximately 1.5-3.5
      times larger than the mean measured 1-year volume change of those structures.
      CONCLUSIONS: Longitudinal deep GM atrophy measures should be interpreted with
      caution. Furthermore, deep GM atrophy measurement techniques require
      substantially improved reproducibility, specifically when aiming for personalized
      medicine.

PMID- 29191871
TI  - MR Imaging Characteristics Associate with Tumor-Associated Macrophages in
      Glioblastoma and Provide an Improved Signature for Survival Prognostication.
AB  - BACKGROUND AND PURPOSE: In glioblastoma, tumor-associated macrophages have tumor
      promoting properties. This study determined whether routine MR imaging features
      could predict molecular subtypes of glioblastoma that differ in the content of
      tumor-associated macrophages. MATERIALS AND METHODS: Seven internally derived MR
      imaging features were assessed in 180 patients, and 25 features from the Visually
      AcceSAble Rembrandt Images feature set were assessed in 164 patients.
      Glioblastomas were divided into subtypes based on the telomere maintenance
      mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT
      ) and the content of tumor-associated macrophages (with [M+] or without [M-] a
      high content of macrophages). The 3 most frequent subtypes (ALT+/M-, ALT-/M+, and
      ALT-/M-) were correlated with MR imaging features and clinical parameters. The
      fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging
      features. RESULTS: Tumors with a regular margin and those lacking a fungating
      margin, an expansive T1/FLAIR ratio, and reduced ependymal extension were more
      frequent in the subgroup of ALT+/M- (P < .05). Radiologic necrosis, lack of
      cystic component (by both criteria), and extensive peritumoral edema were more
      frequent in ALT-/M+ tumors (P < .05). Multivariate testing with a Cox regression
      analysis found the cystic imaging feature was additive to tumor subtype, and O6
      methylguanine methyltransferase (MGMT) status to predict improved patient
      survival (P < .05). CONCLUSIONS: Glioblastomas with tumor-associated macrophages
      are associated with routine MR imaging features consistent with these tumors
      being more aggressive. Inclusion of cystic change with molecular subtypes and
      MGMT status provided a better estimate of survival.

PMID- 29191872
TI  - Influences for Gender Disparity in Academic Neuroradiology.
AB  - BACKGROUND AND PURPOSE: There has been extensive interest in promoting gender
      equality within radiology, a predominately male field. In this study, our aim was
      to quantify gender representation in neuroradiology faculty rankings and
      determine any related factors that may contribute to any such disparity.
      MATERIALS AND METHODS: We evaluated the academic and administrative faculty
      members of neuroradiology divisions for all on-line listed programs in the US and
      Canada. After excluding programs that did not fulfill our selection criteria, we
      generated a short list of 85 US and 8 Canadian programs. We found 465 faculty
      members who met the inclusion criteria for our study. We used Elsevier's SCOPUS
      for gathering the data pertaining to the publications, H-index, citations, and
      tenure of the productivity of each faculty member. RESULTS: Gender disparity was
      insignificant when analyzing academic ranks. There are more men working in
      neuroimaging relative to women (chi2 = 0.46; P = .79). However, gender disparity
      was highly significant for leadership positions in neuroradiology (chi2 = 6.76; P
      = .009). The median H-index was higher among male faculty members (17.5) versus
      female faculty members (9). Female faculty members have odds of 0.84 compared
      with male faculty members of having a higher H-index, adjusting for publications,
      citations, academic ranks, leadership ranks, and interaction between gender and
      publications and gender and citations (9). CONCLUSIONS: Neuroradiology faculty
      members follow the same male predominance seen in many other specialties of
      medicine. In this study, issues such as mentoring, role models, opportunities to
      engage in leadership/research activities, funding opportunities, and mindfulness
      regarding research productivity are explored.

PMID- 29191873
TI  - Time for a Time Window Extension: Insights from Late Presenters in the ESCAPE
      Trial.
AB  - BACKGROUND AND PURPOSE: The safety and efficacy of endovascular therapy for large
      artery stroke in the extended time window is not yet well-established. We
      performed a subgroup analysis on subjects enrolled within an extended time window
      in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic
      Stroke (ESCAPE) trial. MATERIALS AND METHODS: Fifty-nine of 315 subjects (33 in
      the intervention group and 26 in the control group) were randomized in the ESCAPE
      trial between 5.5 and 12 hours after last seen healthy (likely to have groin
      puncture administered 6 hours after that). Treatment effect sizes for all
      relevant outcomes (90-day mRS shift, mRS 0-2, mRS 0-1, and 24-hour NIHSS scores
      and intracerebral hemorrhage) were reported using unadjusted and adjusted
      analyses. RESULTS: There was no evidence of treatment heterogeneity between
      subjects in the early and late windows. Treatment effect favoring intervention
      was seen across all clinical outcomes in the extended time window (absolute risk
      difference of 19.3% for mRS 0-2 at 90 days). There were more asymptomatic
      intracerebral hemorrhage events within the intervention arm (48.5% versus 11.5%,
      P = .004) but no difference in symptomatic intracerebral hemorrhage. CONCLUSIONS:
      Patients with an extended time window could potentially benefit from endovascular
      treatment. Ongoing randomized controlled trials using imaging to identify late
      presenters with favorable brain physiology will help cement the paradigm of using
      time windows to select the population for acute imaging and imaging to select
      individual patients for therapy.

PMID- 29191874
TI  - CT Attenuation Analysis of Carotid Intraplaque Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Intraplaque hemorrhage is considered a leading parameter
      of carotid plaque vulnerability. Our purpose was to assess the CT characteristics
      of intraplaque hemorrhage with histopathologic correlation to identify features
      that allow for confirming or ruling out the intraplaque hemorrhage. MATERIALS AND
      METHODS: This retrospective study included 91 patients (67 men; median age, 65 +/
      7 years; age range, 41-83 years) who underwent CT angiography and carotid
      endarterectomy from March 2010 to May 2013. Histopathologic analysis was
      performed for the tissue characterization and identification of intraplaque
      hemorrhage. Two observers assessed the plaque's attenuation values by using an
      ROI (>= 1 and <=2 mm2). Receiver operating characteristic curve, Mann-Whitney,
      and Wilcoxon analyses were performed. RESULTS: A total of 169 slices were
      assessed (59 intraplaque hemorrhage, 63 lipid-rich necrotic core, and 47
      fibrous); the average values of the intraplaque hemorrhage, lipid-rich necrotic
      core, and fibrous tissue were 17.475 Hounsfield units (HU) and 18.407 HU, 39.476
      HU and 48.048 HU, and 91.66 HU and 93.128 HU, respectively, before and after the
      administration of contrast medium. The Mann-Whitney test showed a statistically
      significant difference of HU values both in basal and after the administration of
      contrast material phase. Receiver operating characteristic analysis showed a
      statistical association between intraplaque hemorrhage and low HU values, and a
      threshold of 25 HU demonstrated the presence of intraplaque hemorrhage with a
      sensitivity and specificity of 93.22% and 92.73%, respectively. The Wilcoxon test
      showed that the attenuation of the plaque before and after administration of
      contrast material is different (intraplaque hemorrhage, lipid-rich necrotic core,
      and fibrous tissue had P values of .006, .0001, and .018, respectively).
      CONCLUSIONS: The results of this preliminary study suggest that CT can be used to
      identify the presence of intraplaque hemorrhage according to the attenuation. A
      threshold of 25 HU in the volume acquired after the administration of contrast
      medium is associated with an optimal sensitivity and specificity. Special care
      should be given to the correct identification of the ROI.

PMID- 29191875
TI  - Lymphographic-Like Technique for the Treatment of Microcystic Lymphatic
      Malformation Components of <3 mm.
AB  - BACKGROUND AND PURPOSE: The treatment of microcystic lymphatic malformations
      remains challenging. Our aim was to describe the lymphographic-like technique, a
      new technique of slow bleomycin infusion for the treatment of microcyst
      components of <3 mm, performed at our institution. MATERIALS AND METHODS: A
      retrospective analysis of a prospectively collected lymphatic malformation data
      base was performed. Patients with at least 1 microcystic lymphatic malformation
      component demonstrated on MR imaging treated by lymphographic-like technique
      bleomycin infusion were included in the study. Patient interviews and MR imaging
      were performed to assess subjective and objective (microcystic lymphatic
      malformation size decrease of >30%) clinical improvement, respectively. Patients
      were reviewed 3 months after each sclerotherapy session. Lymphographic-like
      technique safety and efficacy were assessed. RESULTS: Between January 2012 and
      July 2016, sixteen patients (5 males, 11 females; mean age, 15 years; range, 1-47
      years) underwent the bleomycin lymphographic-like technique for microcystic
      lymphatic malformations. Sixty sclerotherapy sessions were performed, with a mean
      of 4 sessions per patient (range, 1-8 sessions) and a mean follow-up of 26 months
      (range, 5-58 months). We observed no major and 3 minor complications: 1 eyelid
      infection, 1 case of severe postprocedural nausea and vomiting, and 1 case of
      skin discoloration. One patient was lost to follow-up. Overall MR imaging
      objective improvement was observed in 5/16 (31%) patients; overall improvement of
      clinical symptoms was obtained in 93% of treated patients. CONCLUSIONS: The
      bleomycin lymphographic-like technique for microcystic lymphatic malformations is
      safe and feasible with objective improvement in about one-third of patients. MR
      signal intensity changes after the lymphographic-like technique are associated
      with subjective improvement of the patient's symptoms.

PMID- 29191876
TI  - Comment on "Water harvesting from air with metal-organic frameworks powered by
      natural sunlight".
AB  - Kim et al (Reports, 28 April 2017, p. 430) presented results for the solar-driven
      harvesting of water from air via metal-organic frameworks as a prodigious
      potential advance toward remedying global water shortages. Basic thermodynamics
      and a survey of multiple off-the-shelf technologies show that their approach is
      vastly inferior in efficiency (and thereby in feasibility) to available
      alternatives.

PMID- 29191877
TI  - Response to Comment on "Water harvesting from air with metal-organic frameworks
      powered by natural sunlight".
AB  - In their comment, Bui et al argue that the approach we described in our report is
      vastly inferior in efficiency to alternative off-the-shelf technologies. Their
      conclusion is invalid, as they compare efficiencies in completely different
      operating conditions. Here, using heat transfer and thermodynamics principles, we
      show how Bui et al's conclusions about the efficiencies of off-the-shelf
      technologies are fundamentally flawed and inaccurate for the operating conditions
      described in our study.

PMID- 29191880
TI  - Quake warnings, seismic culture.

PMID- 29191882
TI  - Boston University geologist fights for his job.

PMID- 29191883
TI  - Political chill reverses thaw in U.S.-Cuban science.

PMID- 29191878
TI  - The target landscape of clinical kinase drugs.
AB  - Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly
      observed, requiring thorough target deconvolution to understand drug mechanism of
      action. Using chemical proteomics, we analyzed the target spectrum of 243
      clinically evaluated kinase drugs. The data revealed previously unknown targets
      for established drugs, offered a perspective on the "druggable" kinome,
      highlighted (non)kinase off-targets, and suggested potential therapeutic
      applications. Integration of phosphoproteomic data refined drug-affected
      pathways, identified response markers, and strengthened rationale for combination
      treatments. We exemplify translational value by discovering SIK2 (salt-inducible
      kinase 2) inhibitors that modulate cytokine production in primary cells, by
      identifying drugs against the lung cancer survival marker MELK (maternal
      embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3
      ITD-positive acute myeloid leukemia. This resource, available via the
      ProteomicsDB database, should facilitate basic, clinical, and drug discovery
      research and aid clinical decision-making.

PMID- 29191885
TI  - Relativity survives drop test.

PMID- 29191884
TI  - Poachers threaten Balkans' underground biodiversity.

PMID- 29191879
TI  - Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh
      neutrophils.
AB  - Bone marrow-derived myeloid cells can accumulate within tumors and foster cancer
      outgrowth. Local immune-neoplastic interactions have been intensively
      investigated, but the contribution of the systemic host environment to tumor
      growth remains poorly understood. Here, we show in mice and cancer patients (n =
      70) that lung adenocarcinomas increase bone stromal activity in the absence of
      bone metastasis. Animal studies reveal that the cancer-induced bone phenotype
      involves bone-resident osteocalcin-expressing (Ocn+) osteoblastic cells. These
      cells promote cancer by remotely supplying a distinct subset of tumor
      infiltrating SiglecFhigh neutrophils, which exhibit cancer-promoting properties.
      Experimentally reducing Ocn+ cell numbers suppresses the neutrophil response and
      lung tumor outgrowth. These observations posit osteoblasts as remote regulators
      of lung cancer and identify SiglecFhigh neutrophils as myeloid cell effectors of
      the osteoblast-driven protumoral response.

PMID- 29191886
TI  - Automatic error spotter gains in popularity.

PMID- 29191887
TI  - A wet blanket for theories of liquid water on Mars.

PMID- 29191888
TI  - Ice on the run.

PMID- 29191889
TI  - How pterosaurs bred.

PMID- 29191890
TI  - Escaping the traps of your own hunters.

PMID- 29191891
TI  - Bone voyage-Osteoblasts remotely control tumors.

PMID- 29191892
TI  - Navigating in a sea of genes.

PMID- 29191893
TI  - Obesity and the tumor microenvironment.

PMID- 29191894
TI  - Benzene submits to main-group power.

PMID- 29191895
TI  - Insurance for broad genomic tests in oncology.

PMID- 29191897
TI  - Both male and female advisers can "mother".

PMID- 29191896
TI  - Principles for gene drive research.

PMID- 29191898
TI  - Inoculating against misinformation.

PMID- 29191899
TI  - Museum of the Bible: Questionable science.

PMID- 29191900
TI  - Ocean biogeochemistry modeled with emergent trait-based genomics.
AB  - Marine ecosystem models have advanced to incorporate metabolic pathways
      discovered with genomic sequencing, but direct comparisons between models and
      "omics" data are lacking. We developed a model that directly simulates
      metagenomes and metatranscriptomes for comparison with observations. Model
      microbes were randomly assigned genes for specialized functions, and communities
      of 68 species were simulated in the Atlantic Ocean. Unfit organisms were
      replaced, and the model self-organized to develop community genomes and
      transcriptomes. Emergent communities from simulations that were initialized with
      different cohorts of randomly generated microbes all produced realistic vertical
      and horizontal ocean nutrient, genome, and transcriptome gradients. Thus, the
      library of gene functions available to the community, rather than the
      distribution of functions among specific organisms, drove community assembly and
      biogeochemical gradients in the model ocean.

PMID- 29191901
TI  - Stripe order in the underdoped region of the two-dimensional Hubbard model.
AB  - Competing inhomogeneous orders are a central feature of correlated electron
      materials, including the high-temperature superconductors. The two-dimensional
      Hubbard model serves as the canonical microscopic physical model for such
      systems. Multiple orders have been proposed in the underdoped part of the phase
      diagram, which corresponds to a regime of maximum numerical difficulty. By
      combining the latest numerical methods in exhaustive simulations, we uncover the
      ordering in the underdoped ground state. We find a stripe order that has a highly
      compressible wavelength on an energy scale of a few kelvin, with wavelength
      fluctuations coupled to pairing order. The favored filled stripe order is
      different from that seen in real materials. Our results demonstrate the power of
      modern numerical methods to solve microscopic models, even in challenging
      settings.

PMID- 29191902
TI  - Numerical evidence of fluctuating stripes in the normal state of high-Tc cuprate
      superconductors.
AB  - Upon doping, Mott insulators often exhibit symmetry breaking where charge
      carriers and their spins organize into patterns known as stripes. For high
      transition temperature cuprate superconductors, stripes are widely suspected to
      exist in a fluctuating form. We used numerically exact determinant quantum Monte
      Carlo calculations to demonstrate dynamical stripe correlations in the three-band
      Hubbard model, which represents the local electronic structure of the copper
      oxygen plane. Our results, which are robust to varying parameters, cluster size,
      and boundary conditions, support the interpretation of experimental observations
      such as the hourglass magnetic dispersion and the Yamada plot of
      incommensurability versus doping in terms of the physics of fluctuating stripes.
      These findings provide a different perspective on the intertwined orders emerging
      from the cuprates' normal state.

PMID- 29191903
TI  - Observations and modeling of the elastogravity signals preceding direct seismic
      waves.
AB  - After an earthquake, the earliest deformation signals are not expected to be
      carried by the fastest (P) elastic waves but by the speed-of-light changes of the
      gravitational field. However, these perturbations are weak and, so far, their
      detection has not been accurate enough to fully understand their origins and to
      use them for a highly valuable rapid estimate of the earthquake magnitude. We
      show that gravity perturbations are particularly well observed with broadband
      seismometers at distances between 1000 and 2000 kilometers from the source of the
      2011, moment magnitude 9.1, Tohoku earthquake. We can accurately model them by a
      new formalism, taking into account both the gravity changes and the gravity
      induced motion. These prompt elastogravity signals open the window for minute
      time-scale magnitude determination for great earthquakes.

PMID- 29191904
TI  - Organocalcium-mediated nucleophilic alkylation of benzene.
AB  - The electrophilic aromatic substitution of a C-H bond of benzene is one of the
      archetypal transformations of organic chemistry. In contrast, the electron-rich
      pi-system of benzene is highly resistant to reactions with electron-rich and
      negatively charged organic nucleophiles. Here, we report that this previously
      insurmountable electronic repulsion may be overcome through the use of
      sufficiently potent organocalcium nucleophiles. Calcium n-alkyl derivatives
      synthesized by reaction of ethene, but-1-ene, and hex-1-ene with a dimeric
      calcium hydride-react with protio and deutero benzene at 60 degrees C through
      nucleophilic substitution of an aromatic C-D/H bond. These reactions produce the
      n-alkyl benzenes with regeneration of the calcium hydride. Density functional
      theory calculations implicate an unstabilized Meisenheimer complex in the C-H
      activation transition state.

PMID- 29191905
TI  - The image-forming mirror in the eye of the scallop.
AB  - Scallops possess a visual system comprising up to 200 eyes, each containing a
      concave mirror rather than a lens to focus light. The hierarchical organization
      of the multilayered mirror is controlled for image formation, from the component
      guanine crystals at the nanoscale to the complex three-dimensional morphology at
      the millimeter level. The layered structure of the mirror is tuned to reflect the
      wavelengths of light penetrating the scallop's habitat and is tiled with a mosaic
      of square guanine crystals, which reduces optical aberrations. The mirror forms
      images on a double-layered retina used for separately imaging the peripheral and
      central fields of view. The tiled, off-axis mirror of the scallop eye bears a
      striking resemblance to the segmented mirrors of reflecting telescopes.

PMID- 29191906
TI  - Spectroscopic signatures of localization with interacting photons in
      superconducting qubits.
AB  - Quantized eigenenergies and their associated wave functions provide extensive
      information for predicting the physics of quantum many-body systems. Using a
      chain of nine superconducting qubits, we implement a technique for resolving the
      energy levels of interacting photons. We benchmark this method by capturing the
      main features of the intricate energy spectrum predicted for two-dimensional
      electrons in a magnetic field-the Hofstadter butterfly. We introduce disorder to
      study the statistics of the energy levels of the system as it undergoes the
      transition from a thermalized to a localized phase. Our work introduces a many
      body spectroscopy technique to study quantum phases of matter.

PMID- 29191907
TI  - Giant nonlinear response at a plasmonic nanofocus drives efficient four-wave
      mixing.
AB  - Efficient optical frequency mixing typically must accumulate over large
      interaction lengths because nonlinear responses in natural materials are
      inherently weak. This limits the efficiency of mixing processes owing to the
      requirement of phase matching. Here, we report efficient four-wave mixing (FWM)
      over micrometer-scale interaction lengths at telecommunications wavelengths on
      silicon. We used an integrated plasmonic gap waveguide that strongly confines
      light within a nonlinear organic polymer. The gap waveguide intensifies light by
      nanofocusing it to a mode cross-section of a few tens of nanometers, thus
      generating a nonlinear response so strong that efficient FWM accumulates over
      wavelength-scale distances. This technique opens up nonlinear optics to a regime
      of relaxed phase matching, with the possibility of compact, broadband, and
      efficient frequency mixing integrated with silicon photonics.

PMID- 29191908
TI  - Selective increase in CO2 electroreduction activity at grain-boundary surface
      terminations.
AB  - Altering a material's catalytic properties requires identifying structural
      features that give rise to active surfaces. Grain boundaries create strained
      regions in polycrystalline materials by stabilizing dislocations and may provide
      a way to create high-energy surfaces for catalysis that are kinetically trapped.
      Although grain-boundary density has previously been correlated with catalytic
      activity for some reactions, direct evidence that grain boundaries create
      surfaces with enhanced activity is lacking. We used a combination of bulk
      electrochemical measurements and scanning electrochemical cell microscopy with
      submicrometer resolution to show that grain-boundary surface terminations in gold
      electrodes are more active than grain surfaces for electrochemical carbon dioxide
      (CO2) reduction to carbon monoxide (CO) but not for the competing hydrogen (H2)
      evolution reaction. The catalytic footprint of the grain boundary is commensurate
      with its dislocation-induced strain field, providing a strategy for broader
      exploitation of grain-boundary effects in heterogeneous catalysis.

PMID- 29191909
TI  - Egg accumulation with 3D embryos provides insight into the life history of a
      pterosaur.
AB  - Fossil eggs and embryos that provide unique information about the reproduction
      and early growth of vertebrates are exceedingly rare, particularly for
      pterosaurs. Here we report on hundreds of three-dimensional (3D) eggs of the
      species Hamipterus tianshanensis from a Lower Cretaceous site in China, 16 of
      which contain embryonic remains. Computed tomography scanning, osteohistology,
      and micropreparation reveal that some bones lack extensive ossification in
      potentially late-term embryos, suggesting that hatchlings might have been
      flightless and less precocious than previously assumed. The geological context,
      including at least four levels with embryos and eggs, indicates that this deposit
      was formed by a rare combination of events, with storms acting on a nesting
      ground. This discovery supports colonial nesting behavior and potential nesting
      site fidelity in the Pterosauria.

PMID- 29191910
TI  - Host DNases prevent vascular occlusion by neutrophil extracellular traps.
AB  - Platelet and fibrin clots occlude blood vessels in hemostasis and thrombosis.
      Here we report a noncanonical mechanism for vascular occlusion based on
      neutrophil extracellular traps (NETs), DNA fibers released by neutrophils during
      inflammation. We investigated which host factors control NETs in vivo and found
      that two deoxyribonucleases (DNases), DNase1 and DNase1-like 3, degraded NETs in
      circulation during sterile neutrophilia and septicemia. In the absence of both
      DNases, intravascular NETs formed clots that obstructed blood vessels and caused
      organ damage. Vascular occlusions in patients with severe bacterial infections
      were associated with a defect to degrade NETs ex vivo and the formation of
      intravascular NET clots. DNase1 and DNase1-like 3 are independently expressed and
      thus provide dual host protection against deleterious effects of intravascular
      NETs.

PMID- 29191912
TI  - Being out in STEM.

PMID- 29191911
TI  - 3.9 A structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP.
AB  - The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase is a master
      regulator of DNA damage response and replication stress in humans, but the
      mechanism of its activation remains unclear. ATR acts together with its partner
      ATRIP. Using cryo-electron microscopy, we determined the structure of intact Mec1
      Ddc2 (the yeast homolog of ATR-ATRIP), which is poised for catalysis, at a
      resolution of 3.9 angstroms. Mec1-Ddc2 forms a dimer of heterodimers through the
      PRD and FAT domains of Mec1 and the coiled-coil domain of Ddc2. The PRD and
      Bridge domains in Mec1 constitute critical regulatory sites. The activation loop
      of Mec1 is inhibited by the PRD, revealing an allosteric mechanism of kinase
      activation. Our study clarifies the architecture of ATR-ATRIP and provides a
      structural framework for the understanding of ATR regulation.

PMID- 29191913
TI  - Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1.
AB  - The expansion of CD8+CD28- T cells, a population of terminally differentiated
      memory T cells, is one of the most consistent immunological changes in humans
      during aging. CD8+CD28- T cells are highly cytotoxic, and their frequency is
      linked to many age-related diseases. As they do not accumulate in mice, many of
      the molecular mechanisms regulating their fate and function remain unclear. In
      this paper, we find that human CD8+CD28- T cells, under resting conditions, have
      an enhanced capacity to use glycolysis, a function linked to decreased expression
      of the NAD+-dependent protein deacetylase SIRT1. Global gene expression profiling
      identified the transcription factor FoxO1 as a SIRT1 target involved in
      transcriptional reprogramming of CD8+CD28- T cells. FoxO1 is proteasomally
      degraded in SIRT1-deficient CD8+CD28- T cells, and inhibiting its activity in
      resting CD8+CD28+ T cells enhanced glycolytic capacity and granzyme B production
      as in CD8+CD28- T cells. These data identify the evolutionarily conserved SIRT1
      FoxO1 axis as a regulator of resting CD8+ memory T cell metabolism and activity
      in humans.

PMID- 29191915
TI  - Platelets and vascular integrity: how platelets prevent bleeding in inflammation.
AB  - Platelets play a central role in primary hemostasis by forming aggregates that
      plug holes in injured vessels. Half a century ago, detailed studies of the
      microvasculature by electron microscopy revealed that under inflammatory
      conditions that do not induce major disruption to vascular structure, individual
      platelets are mobilized to the vessel wall, where they interact with leukocytes
      and appear to seal gaps that arise between endothelial cells. Recent developments
      in genetic engineering and intravital microscopy have allowed further molecular
      and temporal characterization of these events. Surprisingly, it turns out that
      platelets support the recruitment of leukocytes to sites of inflammation. In
      parallel, however, they exercise their hemostatic function by securing the
      integrity of inflamed blood vessels to prevent bleeding from sites of leukocyte
      infiltration. It thus appears that platelets not only serve in concert as
      building blocks of the hemostatic plug but also act individually as gatekeepers
      of the vascular wall to help preserve vascular integrity while coordinating host
      defense. Variants of this recently appreciated hemostatic function of platelets
      that we refer to as "inflammation-associated hemostasis" are engaged in different
      contexts in which the endothelium is challenged or dysfunctional. Although the
      distinguishing characteristics of these variants and the underlying mechanisms of
      inflammation-associated hemostasis remain to be fully elucidated, they can differ
      notably from those supporting thrombosis, thus presenting therapeutic
      opportunities.

PMID- 29191916
TI  - Duvelisib, a novel oral dual inhibitor of PI3K-delta,gamma, is clinically active
      in advanced hematologic malignancies.
AB  - Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase-delta (PI3K
      delta) and PI3K-gamma in late-stage clinical development for hematologic
      malignancy treatment. This phase 1 study evaluated maximum tolerated dose (MTD),
      pharmacokinetics, pharmacodynamics (PD), efficacy, and safety of duvelisib in 210
      patients with advanced hematologic malignancies. In the dose escalation phase (n
      = 31), duvelisib 8 to 100 mg twice daily was administered, with MTD determined as
      75 mg twice daily. In the expansion phase (n = 179), patients with indolent non
      Hodgkin lymphoma (iNHL), chronic lymphocytic leukemia (CLL), or T-cell lymphoma
      (TCL) were treated with 25 or 75 mg duvelisib twice daily continuously. Single
      dose duvelisib was rapidly absorbed (time to maximum concentration, 1-2 hours),
      with a half-life of 5.2 to 10.9 hours. PD results showed inhibition of phospho
      AKT (S473) in CLL tumor cells following a single dose and near-complete
      inhibition of CLL proliferation (Ki-67) by cycle 2. Clinical responses were seen
      across a range of doses and disease subtypes: iNHL overall response rate, 58% (n
      = 31) with 6 complete responses (CRs); relapsed/refractory CLL, 56% (n = 55) with
      1 CR; peripheral TCL, 50% (n = 16) with 3 CR; and cutaneous TCL, 32% (n = 19).
      Median time to response was ~1.8 months. Severe (grade >=3) adverse events
      occurred in 84% of patients: neutropenia (32%), alanine transaminase increase
      (20%), aspartate transaminase increase (15%), anemia and thrombocytopenia (each
      14%), diarrhea (11%), and pneumonia (10%). These data support further
      investigation of duvelisib in phase 2 and 3 studies. This trial was registered at
      clinicaltrials.gov as #NCT01476657.

PMID- 29191917
TI  - Isolated myelosarcoma is characterized by recurrent NFE2 mutations and concurrent
      preleukemic clones in the bone marrow.

PMID- 29191914
TI  - Resolvins suppress tumor growth and enhance cancer therapy.
AB  - Cancer therapy reduces tumor burden by killing tumor cells, yet it simultaneously
      creates tumor cell debris that may stimulate inflammation and tumor growth. Thus,
      conventional cancer therapy is inherently a double-edged sword. In this study, we
      show that tumor cells killed by chemotherapy or targeted therapy ("tumor cell
      debris") stimulate primary tumor growth when coinjected with a subthreshold
      (nontumorigenic) inoculum of tumor cells by triggering macrophage proinflammatory
      cytokine release after phosphatidylserine exposure. Debris-stimulated tumors were
      inhibited by antiinflammatory and proresolving lipid autacoids, namely resolvin
      D1 (RvD1), RvD2, or RvE1. These mediators specifically inhibit debris-stimulated
      cancer progression by enhancing clearance of debris via macrophage phagocytosis
      in multiple tumor types. Resolvins counterregulate the release of
      cytokines/chemokines, including TNFalpha, IL-6, IL-8, CCL4, and CCL5, by human
      macrophages stimulated with cell debris. These results demonstrate that enhancing
      endogenous clearance of tumor cell debris is a new therapeutic target that may
      complement cytotoxic cancer therapies.

PMID- 29191918
TI  - Pml nuclear body disruption cooperates in APL pathogenesis and impairs DNA damage
      repair pathways in mice.
AB  - A hallmark of acute promyelocytic leukemia (APL) is altered nuclear architecture,
      with disruption of promyelocytic leukemia (PML) nuclear bodies (NBs) mediated by
      the PML-retinoic acid receptor alpha (RARalpha) oncoprotein. To address whether
      this phenomenon plays a role in disease pathogenesis, we generated a knock-in
      mouse model with NB disruption mediated by 2 point mutations (C62A/C65A) in the
      Pml RING domain. Although no leukemias developed in PmlC62A/C65A mice, these
      transgenic mice also expressing RARalpha linked to a dimerization domain (p50
      RARalpha model) exhibited a doubling in the rate of leukemia, with a reduced
      latency period. Additionally, we found that response to targeted therapy with all
      trans retinoic acid in vivo was dependent on NB integrity. PML-RARalpha is
      recognized to be insufficient for development of APL, requiring acquisition of
      cooperating mutations. We therefore investigated whether NB disruption might be
      mutagenic. Compared with wild-type cells, primary PmlC62A/C65A cells exhibited
      increased sister-chromatid exchange and chromosome abnormalities. Moreover,
      functional assays showed impaired homologous recombination (HR) and nonhomologous
      end-joining (NHEJ) repair pathways, with defective localization of Brca1 and
      Rad51 to sites of DNA damage. These data directly demonstrate that Pml NBs are
      critical for DNA damage responses, and suggest that Pml NB disruption is a
      central contributor to APL pathogenesis.

PMID- 29191919
TI  - On type 1 diabetes mellitus pathogenesis.
AB  - Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of beta
      cells of the endocrine pancreas. Pathogenesis of T1DM is different from that of
      type 2 diabetes mellitus, where both insulin resistance and reduced secretion of
      insulin by the beta cells play a synergistic role. We will present genetic,
      environmental and immunologic factors that destroy beta cells of the endocrine
      pancreas and lead to insulin deficiency. The process of autoimmune destruction
      takes place in genetically susceptible individuals under the triggering effect of
      one or more environmental factors and usually progresses over a period of many
      months to years, during which period patients are asymptomatic and euglycemic,
      but positive for relevant autoantibodies. Symptomatic hyperglycemia and frank
      diabetes occur after a long latency period, which reflects the large percentage
      of beta cells that need to be destroyed before overt diabetes become evident.

PMID- 29191920
TI  - Combined test of serum CgA and NSE improved the power of prognosis prediction of
      NF-pNETs.
AB  - PURPOSE: Chromogranin A (CgA) and neuron-specific enolase (NSE) are important
      markers for neuroendocrine tumors; however, the clinical value of combining these
      markers has not been well studied. In this study, we investigated the utility of
      each marker individually and in combination for patients with nonfunctional
      pancreatic neuroendocrine tumors (NF-pNETs). PATIENTS AND METHODS: In this study,
      NF-pNET patients and controls were recruited from December 2011 to March 2016;
      784 serum samples from peripheral vein were collected. The clinical
      characteristics and biomarker values of all the individuals were recorded and
      analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating
      characteristic curves were constructed to assess the diagnostic predictive
      values; sensitivity and specificity were calculated to determine the cut-off
      value. Therapeutic responses reflected on the changes of the biomarkers'
      concentration were assessed by the RECIST criterion. Clinical relations between
      the prognosis and the biomarker values were also analyzed. Statistical
      significance was defined as P value less than 0.05. RESULTS: Among the 167 NF
      pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean
      CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 MUg/L (P < 0.05),
      respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2,
      P < 0.05); the linear regression relationships were found between the tumor
      burdens (both in pancreas and liver) and CgA concentration (P < 0.001); changes
      in CgA and NSE concentrations also reflect treatment response (P < 0.001).
      CONCLUSION: CgA and NSE are important diagnostic and follow-up markers in
      patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more
      accuracy than individual values of CgA and NSE at predicting prognosis and
      disease progression.

PMID- 29191921
TI  - Selective EGFR (Epidermal Growth Factor Receptor) Deletion in Myeloid Cells
      Limits Atherosclerosis-Brief Report.
AB  - OBJECTIVE: To determine the consequences of specific inhibition of EGFR
      (epidermal growth factor receptor) in myeloid cells in atherosclerosis
      development. APPROACH AND RESULTS: Atherosclerotic lesion size was significantly
      reduced in irradiated Ldlr-/- mice reconstituted with LysMCre+Egfrlox/lox bone
      marrow, compared with chimeric Ldlr-/- mice reconstituted with LysMCre
      Egfrlox/lox bone marrow, after 4 (-43%; P<0.05), 7 (-34%; P<0.05), and 12 weeks (
      54%; P<0.001) of high-fat diet. Reduction of lesion size was associated with
      marked reduction in macrophage accumulation and necrotic core size. Specific
      deletion of Egfr in myeloid cells reduced TNF-alpha (tumor necrosis factor-alpha)
      and IL (interleukin)-6 production by stimulated macrophages but had no effect on
      IL-10 and IL-12p70 secretion. Finally, we found that myeloid deletion of Egfr
      limited cytoskeletal rearrangements and also lipid uptake by macrophages through
      a downregulation of the scavenger receptor CD36 (cluster of differentiation 36).
      CONCLUSIONS: Gene deletion of Egfr in myeloid cells limits IL-6 and TNF-alpha
      production, lipid uptake, and consecutively reduces atherosclerosis development.

PMID- 29191922
TI  - Adventitial Sca1+ Cells Transduced With ETV2 Are Committed to the Endothelial
      Fate and Improve Vascular Remodeling After Injury.
AB  - OBJECTIVE: Vascular adventitial Sca1+ (stem cell antigen-1) progenitor cells
      preferentially differentiate into smooth muscle cells, which contribute to
      vascular remodeling and neointima formation in vessel grafts. Therefore,
      directing the differentiation of Sca1+ cells toward the endothelial lineage could
      represent a new therapeutic strategy against vascular disease. APPROACH AND
      RESULTS: We thus developed a fast, reproducible protocol based on the single-gene
      transfer of ETV2 (ETS variant 2) to differentiate Sca1+ cells toward the
      endothelial fate and studied the effect of cell conversion on vascular
      hyperplasia in a model of endothelial injury. After ETV2 transduction, Sca1+
      adventitial cells presented a significant increase in the expression of early
      endothelial cell genes, including VE-cadherin, Flk-1, and Tie2 at the mRNA and
      protein levels. ETV2 overexpression also induced the downregulation of a panel of
      smooth muscle cell and mesenchymal genes through epigenetic regulations, by
      decreasing the expression of DNA-modifying enzymes ten-eleven translocation
      dioxygenases. Adventitial Sca1+ cells grafted on the adventitial side of wire
      injured femoral arteries increased vascular wall hyperplasia compared with
      control arteries with no grafted cells. Arteries seeded with ETV2-transduced
      cells, on the contrary, showed reduced hyperplasia compared with control.
      CONCLUSIONS: These data give evidence that the genetic manipulation of vascular
      progenitors is a promising approach to improve vascular function after
      endothelial injury.

PMID- 29191924
TI  - Both Autocrine Signaling and Paracrine Signaling of HB-EGF Enhance Ocular
      Neovascularization.
AB  - OBJECTIVE: The incidence of blindness is increasing because of the increase in
      abnormal ocular neovascularization. Anti-VEGF (vascular endothelial growth
      factor) therapies have led to good results, although they are not a cure for the
      blindness. The purpose of this study was to determine what role HB-EGF (heparin
      binding epidermal growth factor-like growth factor) plays in ocular angiogenesis.
      APPROACH AND RESULTS: We examined the role played by HB-EGF in ocular
      neovascularization in 2 animal models of neovascularization: laser-induced
      choroidal neovascularization (CNV) and oxygen-induced retinopathy. We also
      studied human retinal microvascular endothelial cells in culture. Our results
      showed that the neovascularization was decreased in both the CNV and oxygen
      induced retinopathy models in HB-EGF conditional knockout mice compared with that
      in wild-type mice. Moreover, the expressions of HB-EGF and VEGF were increased
      after laser-induced CNV and oxygen-induced retinopathy, and their expression
      sites were located around the neovascular areas. Exposure of human retinal
      microvascular endothelial cells to HB-EGF and VEGF increased their proliferation
      and migration, and CRM-197 (cross-reactive material-197), an HB-EGF inhibitor,
      decreased the HB-EGF-induced and VEGF-induced cell proliferation and migration.
      VEGF increased the expression of HB-EGF mRNA. VEGF-dependent activation of EGFR
      (epidermal growth factor receptor)/ERK1/2 (extracellular signal-regulated kinase
      1/2) signaling and cell proliferation of endothelial cells required stimulation
      of the ADAM17 (a disintegrin and metalloprotease) and ADAM12. CRM-197 decreased
      the grades of the fluorescein angiograms and size of the CNV areas in marmoset
      monkeys. CONCLUSIONS: These findings suggest that HB-EGF plays an important role
      in the development of CNV. Therefore, further investigations of HB-EGF are needed
      as a potential therapeutic target in the treatment of exudative age-related
      macular degeneration.

PMID- 29191923
TI  - Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases.
AB  - Cardiovascular disease is a leading cause of morbidity and mortality in the
      Western world. Studies of sortilin's influence on cardiovascular and metabolic
      diseases goes far beyond the genome-wide association studies that have revealed
      an association between cardiovascular diseases and the 1p13 locus that encodes
      sortilin. Emerging evidence suggests a significant role of sortilin in the
      pathogenesis of vascular and metabolic diseases; this includes type II diabetes
      mellitus via regulation of insulin resistance, atherosclerosis through arterial
      wall inflammation and calcification, and dysregulated lipoprotein metabolism.
      Sortilin is also known for its functional role in neurological disorders. It
      serves as a key receptor for cytokines, lipids, and enzymes and participates in
      pathological cargo loading to and trafficking of extracellular vesicles. This
      article provides a comprehensive review of sortilin's contributions to
      cardiovascular and metabolic diseases but focuses particularly on
      atherosclerosis. We summarize recent clinical findings that suggest that sortilin
      may be a cardiovascular risk biomarker and also discuss sortilin as a potential
      drug target.

PMID- 29191925
TI  - Inhalation of Fine Particulate Matter Impairs Endothelial Progenitor Cell
      Function Via Pulmonary Oxidative Stress.
AB  - OBJECTIVE: Exposure to fine particulate matter (PM2.5) air pollution is
      associated with the depletion of circulating endothelial progenitor cells (EPCs),
      as well as vascular injury and dysfunction. Nevertheless, it remains unclear
      whether PM2.5 exposure leads to significant impairments in EPC function. Hence,
      we studied the effects of PM2.5 on EPC-mediated recovery of vascular perfusion
      after hindlimb ischemia and examined the mechanisms whereby PM2.5 exposure
      affects EPC abundance and function. APPROACH AND RESULTS: In comparison with EPCs
      isolated from mice breathing filtered air, EPCs from mice exposed for 9
      consecutive days (6 hours per day) to concentrated ambient PM2.5 (CAP) had
      defects in both proliferation and tube formation. However, CAP exposure of mice
      overexpressing extracellular superoxide dismutase (ecSOD-Tg) in the lungs did not
      affect EPC tube formation. Exposure to CAP also suppressed circulating EPC
      levels, VEGF (vascular endothelial growth factor)-stimulated aortic Akt
      phosphorylation, and plasma NO levels in wild-type but not in ecSOD-Tg mice. EPCs
      from CAP-exposed wild-type mice failed to augment basal recovery of hindlimb
      perfusion when injected into unexposed mice subjected to hindlimb ischemia;
      however, these deficits in recovery of hindlimb perfusion were absent when using
      EPCs derived from CAP-exposed ecSOD-Tg mice. The improved reparative function of
      EPCs from CAP-exposed ecSOD-Tg mice was also reflected by greater expression of
      Mmp-9 and Nos3 when compared with EPCs from CAP-exposed wild-type mice.
      CONCLUSIONS: Exposure to PM2.5 impairs EPC abundance and function and prevents
      EPC-mediated vascular recovery after hindlimb ischemia. This defect is
      attributed, in part, to pulmonary oxidative stress and was associated with
      vascular VEGF resistance and a decrement in NO bioavailability.

PMID- 29191926
TI  - Molecular Ultrasound Imaging of Junctional Adhesion Molecule A Depicts Acute
      Alterations in Blood Flow and Early Endothelial Dysregulation.
AB  - OBJECTIVE: The junctional adhesion molecule A (JAM-A) is physiologically located
      in interendothelial tight junctions and focally redistributes to the luminal
      surface of blood vessels under abnormal shear and flow conditions accompanying
      atherosclerotic lesion development. Therefore, JAM-A was evaluated as a target
      for molecularly targeted ultrasound imaging of transient endothelial dysfunction
      under acute blood flow variations. APPROACH AND RESULTS: Flow-dependent
      endothelial dysfunction was induced in apolipoprotein E-deficient mice (n=43) by
      carotid partial ligation. JAM-A expression was investigated by molecular
      ultrasound using antibody-targeted poly(n-butyl cyanoacrylate) microbubbles and
      validated with immunofluorescence. Flow disturbance and arterial remodeling were
      assessed using functional ultrasound. Partial ligation led to an immediate drop
      in perfusion at the ligated side and a direct compensatory increase at the
      contralateral side. This was accompanied by a strongly increased JAM-A expression
      and JAM-A-targeted microbubbles binding at the partially ligated side and by a
      moderate and temporary increase in the contralateral artery (~14* [P<0.001] and
      ~5* [P<0.001] higher than control, respectively), both peaking after 2 weeks.
      Subsequently, although JAM-A expression and JAM-A-targeted microbubbles binding
      persisted at a higher level at the partially ligated side, it completely
      normalized within 4 weeks at the contralateral side. CONCLUSIONS: Temporary blood
      flow variations induce endothelial rearrangement of JAM-A, which can be
      visualized using JAM-A-targeted microbubbles. Thus, JAM-A may be considered as a
      marker of acute endothelial activation and dysfunction. Its imaging may
      facilitate the early detection of cardiovascular risk areas, and it enables the
      therapeutic prevention of their progression toward an irreversible pathological
      state.

PMID- 29191927
TI  - Associations Between Residential Proximity to Traffic and Vascular Disease in a
      Cardiac Catheterization Cohort.
AB  - OBJECTIVE: Exposure to mobile source emissions is nearly ubiquitous in developed
      nations and is associated with multiple adverse health outcomes. There is an
      ongoing need to understand the specificity of traffic exposure associations with
      vascular outcomes, particularly in individuals with cardiovascular disease.
      APPROACH AND RESULTS: We performed a cross-sectional study using 2124 individuals
      residing in North Carolina, United States, who received a cardiac catheterization
      at the Duke University Medical Center. Traffic-related exposure was assessed via
      2 metrics: (1) the distance between the primary residence and the nearest major
      roadway; and (2) location of the primary residence in regions defined based on
      local traffic patterns. We examined 4 cardiovascular disease outcomes:
      hypertension, peripheral arterial disease, the number of diseased coronary
      vessels, and recent myocardial infarction. Statistical models were adjusted for
      race, sex, smoking, type 2 diabetes mellitus, body mass index, hyperlipidemia,
      and home value. Results are expressed in terms of the odds ratio (OR). A 23%
      decrease in residential distance to major roadways was associated with higher
      prevalence of peripheral arterial disease (OR=1.29; 95% confidence interval, 1.08
      1.55) and hypertension (OR=1.15; 95% confidence interval, 1.01-1.31).
      Associations with peripheral arterial disease were strongest in men (OR=1.42; 95%
      confidence interval, 1.17-1.74) while associations with hypertension were
      strongest in women (OR=1.21; 95% confidence interval, 0.99-1.49). Neither
      myocardial infarction nor the number of diseased coronary vessels were associated
      with traffic exposure. CONCLUSIONS: Traffic-related exposure is associated with
      peripheral arterial disease and hypertension while no associations are observed
      for 2 coronary-specific vascular outcomes.

PMID- 29191930
TI  - NHS urgent facilities repairs: is your hospital on the critical list?

PMID- 29191928
TI  - Sustained Activation of Rho GTPases Promotes a Synthetic Pulmonary Artery Smooth
      Muscle Cell Phenotype in Neprilysin Null Mice.
AB  - OBJECTIVE: Pulmonary artery smooth muscle cells (PASMCs) from neprilysin (NEP)
      null mice exhibit a synthetic phenotype and increased activation of Rho GTPases
      compared with their wild-type counterparts. Although Rho GTPases are known to
      promote a contractile SMC phenotype, we hypothesize that their sustained activity
      decreases SM-protein expression in these cells. APPROACH AND RESULTS: PASMCs
      isolated from wild-type and NEP-/- mice were used to assess levels of SM-proteins
      (SM-actin, SM-myosin, SM22, and calponin) by Western blotting, and were lower in
      NEP-/- PASMCs compared with wild-type. Rac and Rho (ras homology family member)
      levels and activity were higher in NEP-/- PASMCs, and ShRNA to Rac and Rho
      restored SM-protein, and attenuated the enhanced migration and proliferation of
      NEP-/- PASMCs. SM-gene repressors, p-Elk-1, and Klf4 (Kruppel lung factor 4),
      were higher in NEP-/- PASMCs and decreased by shRNA to Rac and Rho. Costimulation
      of wild-type PASMCs with PDGF (platelet-derived growth factor) and the NEP
      substrate, ET-1 (endothelin-1), increased Rac and Rho activity, and decreased SM
      protein levels mimicking the NEP knock-out phenotype. Activation of Rac and Rho
      and downstream effectors was observed in lung tissue from NEP-/- mice and humans
      with chronic obstructive pulmonary disease. CONCLUSIONS: Sustained Rho activation
      in NEP-/- PASMCs is associated with a decrease in SM-protein levels and increased
      migration and proliferation. Inactivation of RhoGDI (Rho guanine dissociation
      inhibitor) and RhoGAP (Rho GTPase activating protein) by phosphorylation may
      contribute to prolonged activation of Rho in NEP-/- PASMCs. Rho GTPases may thus
      have a role in integration of signals between vasopeptides and growth factor
      receptors and could influence pathways that suppress SM-proteins to promote a
      synthetic phenotype.

PMID- 29191929
TI  - Correction: Inhibition of mTORC1 Kinase Activates Smads 1 and 5 but Not Smad8 in
      Human Prostate Cancer Cells, Mediating Cytostatic Response to Rapamycin.

PMID- 29191931
TI  - European normative values for physical fitness in children and adolescents aged 9
      17 years: results from 2 779 165 Eurofit performances representing 30 countries.
AB  - OBJECTIVE: To develop sex-specific and age-specific normative values for the nine
      Eurofit tests in European children and adolescents aged 9-17 years. METHODS: A
      systematic review was undertaken to identify papers that explicitly reported
      descriptive results for at least one of nine Eurofit tests (measuring balance,
      muscular strength, muscular endurance, muscular power, flexibility, speed, speed
      agility and cardiorespiratory fitness (CRF)) on children and adolescents. Data
      were included on apparently healthy (free from known disease/injury) children and
      adolescents aged 9-17 years. Following harmonisation for methodological variation
      where appropriate, pseudodata were generated using Monte Carlo simulation, with
      population-weighted sex-specific and age-specific normative centiles generated
      using the Lambda Mu Sigma (LMS) method. Sex-specific and age-specific differences
      were expressed as standardised differences in means, with the percentage of
      children and adolescents with healthy CRF estimated at the sex-age level.
      RESULTS: Norms were displayed as tabulated centiles and as smoothed centile
      curves for the nine Eurofit tests. The final dataset included 2 779 165 results
      on children and adolescents from 30 European countries, extracted from 98
      studies. On average, 78% of boys (95% CI 72% to 85%) and 83% of girls (95% CI 71%
      to 96%) met the standards for healthy CRF, with the percentage meeting the
      standards decreasing with age. Boys performed substantially (standardised
      differences >0.2) better than girls on muscular strength, muscular power,
      muscular endurance, speed-agility and CRF tests, but worse on the flexibility
      test. Physical fitness generally improved at a faster rate in boys than in girls,
      especially during the teenage years. CONCLUSION: This study provides the largest
      and most geographically representative sex-specific and age-specific European
      normative values for children and adolescents, which have utility for health and
      fitness screening, profiling, monitoring and surveillance.

PMID- 29191933
TI  - The BMJ charity appeal Christmas 2017: Medecins Sans Frontieres' volunteer
      doctors need your support.

PMID- 29191932
TI  - So you want to understand subsequent injuries better? Start by understanding the
      minimum data collection and reporting requirements.

PMID- 29191934
TI  - MANAGEMENT OF ENDOCRINE DISEASE: Fertility, pregnancy and lactation in women with
      adrenal insufficiency.
AB  - With the introduction of hormonal substitution therapy in the 1950s, adrenal
      insufficiency (AI) has been turned into a manageable disease in pregnant women.
      In fact, in the light of glucocorticoid replacement therapy and improved
      obstetric care, it is realistic to expect good maternal and fetal outcomes in
      patients with AI. However, there are still a number of challenges such as
      establishing the diagnosis of AI in pregnant women and optimizing the treatment
      of AI and related comorbidities prior to as well as during pregnancy. Clinical
      and biochemical diagnoses of a new-onset AI may be challenging because of
      overlapping symptoms of normal pregnancy as well as pregnancy-induced changes in
      cortisol values. Physiological changes occurring during pregnancy should be taken
      into account while adjusting the substitution therapy. The high proportion of
      reported adrenal crisis in pregnant women with AI highlights persistent problems
      in this particular clinical situation. Due to the rarity of the disease, there is
      no prospective data-guiding management of pregnancy in patients with known AI.
      The aim of this review is to summarize the maternal and fetal outcomes based on
      recently published case reports in patients with AI and to suggest a practical
      approach to diagnose and manage AI in pregnancy.

PMID- 29191936
TI  - High court finds that tribunal treated GP too leniently.

PMID- 29191940
TI  - Loss of cellular FLICE-inhibitory protein promotes acute cholestatic liver injury
      and inflammation from bile duct ligation.
AB  - Cholestatic liver injury results from impaired bile flow or metabolism and
      promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate
      in cholestasis induce apoptosis and contribute to early cholestatic liver injury,
      which is amplified by accompanying inflammation. The aim of the current study was
      to evaluate the role of the antiapoptotic caspase 8-homolog cellular FLICE
      inhibitory (cFLIP) protein during acute cholestatic liver injury. Transgenic mice
      exhibiting hepatocyte-specific deletion of cFLIP (cFLIP-/-) were used for in vivo
      and in vitro analysis of cholestatic liver injury using bile duct ligation (BDL)
      and the addition of bile acids ex vivo. Loss of cFLIP in hepatocytes promoted
      acute cholestatic liver injury early after BDL, which was characterized by a
      rapid release of proinflammatory and chemotactic cytokines (TNF, IL-6, IL-1beta,
      CCL2, CXCL1, and CXCL2), an increased presence of CD68+ macrophages and an influx
      of neutrophils in the liver, and resulting apoptotic and necrotic hepatocyte cell
      death. Mechanistically, liver injury in cFLIP-/- mice was aggravated by reactive
      oxygen species, and sustained activation of the JNK signaling pathway. In
      parallel, cytoprotective NF-kappaB p65, A20, and the MAPK p38 were inhibited.
      Increased injury in cFLIP-/- mice was accompanied by activation of hepatic
      stellate cells and profibrogenic regulators. The antagonistic caspase 8-homolog
      cFLIP is a critical regulator of acute, cholestatic liver injury. NEW &
      NOTEWORTHY The current paper explores the role of a classical modulator of
      hepatocellular apoptosis in early, cholestatic liver injury. These include
      activation of NF-kappaB and MAPK signaling, production of inflammatory cytokines,
      and recruitment of neutrophils in response to cholestasis. Because these
      signaling pathways are currently exploited in clinical trials for the treatment
      of nonalcoholic steatohepatitis and cirrhosis, the current data will help in the
      development of novel pharmacological options in these indications.

PMID- 29191937
TI  - Peroxynitrite preferentially oxidizes the dithiol redox motifs of protein
      disulfide isomerase.
AB  - Protein-disulfide isomerase (PDI) is a ubiquitous dithiol-disulfide
      oxidoreductase that performs an array of cellular functions, such as cellular
      signaling and responses to cell-damaging events. PDI can become dysfunctional by
      post-translational modifications, including those promoted by biological
      oxidants, and its dysfunction has been associated with several diseases in which
      oxidative stress plays a role. Because the kinetics and products of the reaction
      of these oxidants with PDI remain incompletely characterized, we investigated the
      reaction of PDI with the biological oxidant peroxynitrite. First, by determining
      the rate constant of the oxidation of PDI's redox-active Cys residues (Cys53 and
      Cys397) by hydrogen peroxide (k = 17.3 +/- 1.3 m-1 s-1 at pH 7.4 and 25  degrees
      C), we established that the measured decay of the intrinsic PDI fluorescence is
      appropriate for kinetic studies. The reaction of these PDI residues with
      peroxynitrite was considerably faster (k = (6.9 +/- 0.2) * 104 m-1 s-1), and both
      Cys residues were kinetically indistinguishable. Limited proteolysis, kinetic
      simulations, and MS analyses confirmed that peroxynitrite preferentially oxidizes
      the redox-active Cys residues of PDI to the corresponding sulfenic acids, which
      reacted with the resolving thiols at the active sites to produce disulfides (i.e.
      Cys53-Cys56 and Cys397-Cys400). A fraction of peroxynitrite, however, decayed to
      radicals that hydroxylated and nitrated other active-site residues (Trp52,
      Trp396, and Tyr393). Excess peroxynitrite promoted further PDI oxidation,
      nitration, inactivation, and covalent oligomerization. We conclude that these PDI
      modifications may contribute to the pathogenic mechanism of several diseases
      associated with dysfunctional PDI.

PMID- 29191939
TI  - Effects of hypothalamic leptin gene therapy on osteopetrosis in leptin-deficient
      mice.
AB  - Impaired resorption of cartilage matrix deposited during endochondral
      ossification is a defining feature of juvenile osteopetrosis. Growing, leptin
      deficient ob/ob mice exhibit a mild form of osteopetrosis. However, the extent to
      which the disease is (1) self-limiting and (2) reversible by leptin treatment is
      unknown. We addressed the first question by performing histomorphometric analysis
      of femurs in rapidly growing (2-month-old), slowly growing (4-month-old) and
      skeletally mature (6-month-old) wild-type (WT) and ob/ob male mice. Absent by 6
      months of age in WT mice, cartilage matrix persisted to varying extents in distal
      femur epiphysis, metaphysis and diaphysis in ob/ob mice, suggesting that the
      osteopetrotic phenotype is not entirely self-limiting. To address the second
      question, we employed hypothalamic recombinant adeno-associated virus (rAAV) gene
      therapy to restore leptin signaling in ob/ob mice. Two-month-old mice were
      randomized to one of the three groups: (1) untreated control, (2) rAAV-Leptin or
      (3) control vector rAAV-green fluorescent protein and vectors injected
      intracerebroventricularly. Seven months later, rAAV-leptin-treated mice exhibited
      no cartilage in the metaphysis and greatly reduced cartilage in the epiphysis and
      diaphysis. At the cellular level, the reduction in cartilage was associated with
      increased bone turnover. These findings (1) support the concept that leptin is
      important for normal replacement of cartilage by bone, and (2) demonstrate that
      osteopetrosis in ob/ob mice is bone-compartment-specific and reversible by leptin
      at skeletal sites capable of undergoing robust bone turnover.

PMID- 29191938
TI  - International External Validation Study of the 2014 European Society of
      Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic
      Cardiomyopathy (EVIDENCE-HCM).
AB  - BACKGROUND: Identification of people with hypertrophic cardiomyopathy (HCM) who
      are at risk of sudden cardiac death (SCD) and require a prophylactic implantable
      cardioverter defibrillator is challenging. In 2014, the European Society of
      Cardiology proposed a new risk stratification method based on a risk prediction
      model (HCM Risk-SCD) that estimates the 5-year risk of SCD. The aim was to
      externally validate the 2014 European Society of Cardiology recommendations in a
      geographically diverse cohort of patients recruited from the United States,
      Europe, the Middle East, and Asia. METHODS: This was an observational,
      retrospective, longitudinal cohort study. RESULTS: The cohort consisted of 3703
      patients. Seventy three (2%) patients reached the SCD end point within 5 years of
      follow-up (5-year incidence, 2.4% [95% confidence interval {CI}, 1.9-3.0]). The
      validation study revealed a calibration slope of 1.02 (95% CI, 0.93-1.12), C
      index of 0.70 (95% CI, 0.68-0.72), and D-statistic of 1.17 (95% CI, 1.05-1.29).
      In a complete case analysis (n= 2147; 44 SCD end points at 5 years), patients
      with a predicted 5-year risk of <4% (n=1524; 71%) had an observed 5-year SCD
      incidence of 1.4% (95% CI, 0.8-2.2); patients with a predicted risk of >=6%
      (n=297; 14%) had an observed SCD incidence of 8.9% (95% CI, 5.96-13.1) at 5
      years. For every 13 (297/23) implantable cardioverter defibrillator implantations
      in patients with an estimated 5-year SCD risk >=6%, 1 patient can potentially be
      saved from SCD. CONCLUSIONS: This study confirms that the HCM Risk-SCD model
      provides accurate prognostic information that can be used to target implantable
      cardioverter defibrillator therapy in patients at the highest risk of SCD.

PMID- 29191941
TI  - Genetic deletion of the circadian clock transcription factor BMAL1 and chronic
      alcohol consumption differentially alter hepatic glycogen in mice.
AB  - Multiple metabolic pathways exhibit time-of-day-dependent rhythms that are
      controlled by the molecular circadian clock. We have shown that chronic alcohol
      is capable of altering the molecular clock and diurnal oscillations in several
      elements of hepatic glycogen metabolism ( 19 , 44 ). Herein, we sought to
      determine whether genetic disruption of the hepatocyte clock differentially
      impacts hepatic glycogen content in chronic alcohol-fed mice. Male hepatocyte
      specific BMAL1 knockout (HBK) and littermate controls were fed control or alcohol
      containing diets for 5 wk to alter hepatic glycogen content. Glycogen displayed a
      significant diurnal rhythm in livers of control genotype mice fed the control
      diet. While rhythmic, alcohol significantly altered the diurnal oscillation of
      glycogen in livers of control genotype mice. The glycogen rhythm was mildly
      altered in livers of control-fed HBK mice. Importantly, glycogen content was
      arrhythmic in livers of alcohol-fed HBK mice. Consistent with these changes in
      hepatic glycogen content, we observed that some glycogen and glucose metabolism
      genes were differentially altered by chronic alcohol consumption in livers of HBK
      and littermate control mice. Diurnal rhythms in glycogen synthase (mRNA and
      protein) were significantly altered by alcohol feeding and clock disruption.
      Alcohol consumption significantly altered Gck, Glut2, and Ppp1r3g rhythms in
      livers of control genotype mice, with diurnal rhythms of Pklr, Glut2, Ppp1r3c,
      and Ppp1r3g further disrupted (dampened or arrhythmic) in livers of HBK mice.
      Taken together, these findings show that chronic alcohol consumption and
      hepatocyte clock disruption differentially influence the diurnal rhythm of
      glycogen and various key glycogen metabolism-related genes in the liver. NEW &
      NOTEWORTHY We report that circadian clock disruption exacerbates alcohol-mediated
      alterations in hepatic glycogen. We observed differential responsiveness in
      diurnal rhythms of glycogen and glycogen metabolism genes and proteins in livers
      of hepatocyte-specific BMAL1 knockout and littermate control mice fed alcohol.
      Our findings provide new insights into potential mechanisms by which alcohol
      alters glycogen, an important energy source for liver and other organs.

PMID- 29191942
TI  - beta-PIX plays an important role in regulation of intestinal epithelial
      restitution by interacting with GIT1 and Rac1 after wounding.
AB  - Early gut mucosal restitution is a process by which intestinal epithelial cells
      (IECs) migrate over the wounded area, and its defective regulation occurs
      commonly in various critical pathological conditions. This rapid
      reepithelialization is mediated by different activating small GTP-binding
      proteins, but the exact mechanism underlying this process remains largely
      unknown. Recently, it has been reported that interaction between p21-activated
      kinase-interacting exchange factor (beta-PIX) and G protein-coupled receptor
      kinase-interacting protein 1 (GIT1) activates small GTPases and plays an
      important role in the regulation of cell motility. Here, we show that induced
      association of beta-PIX with GIT1 is essential for the stimulation of IEC
      migration after wounding by activating Rac1. Levels of beta-PIX and GIT1 proteins
      and their association in differentiated IECs (line of IEC-Cdx2L1) were much
      higher than those observed in undifferentiated IECs (line of IEC-6), which was
      associated with an increase in IEC migration after wounding. Decreased levels of
      endogenous beta-PIX by its gene-silencing destabilized beta-PIX/GIT1 complexes,
      repressed Rac1 activity and inhibited cell migration over the wounded area. In
      contrast, ectopic overexpression of beta-PIX increased the levels of beta
      PIX/GIT1 complexes, stimulated Rac1 activity, and enhanced intestinal epithelial
      restitution. Increased levels of cellular polyamines also stimulated beta
      PIX/GIT1 association, increased Rac1 activity, and promoted the epithelial
      restitution. Moreover, polyamine depletion decreased cellular abundances of beta
      PIX/GIT1 complex and repressed IEC migration after wounding, which was rescued by
      ectopic overexpression of beta-PIX or GIT1. These results indicate that beta
      PIX/GIT1/Rac1 association is necessary for stimulation of IEC migration after
      wounding and that this signaling pathway is tightly regulated by cellular
      polyamines. NEW & NOTEWORTHY Our current study demonstrates that induced
      association of beta-PIX with GIT1 is essential for the stimulation of intestinal
      epithelial restitution by activating Rac1, and this signaling pathway is tightly
      regulated by cellular polyamines.

PMID- 29191944
TI  - NHS advises GPs not to prescribe "low value" drugs.

PMID- 29191943
TI  - Novel therapies for unresectable and metastatic melanoma.

PMID- 29191945
TI  - Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable
      with romiplostim.
AB  - Congenital amegakaryocytic thrombocytopenia (CAMT) is an inherited disorder
      characterized at birth by thrombocytopenia with reduced megakaryocytes, which
      evolves into generalized bone marrow aplasia during childhood. Although CAMT is
      genetically heterogeneous, mutations of MPL, the gene encoding for the receptor
      of thrombopoietin (THPO), are the only known disease-causing alterations. We
      identified a family with three children affected with CAMT caused by a homozygous
      mutation (p.R119C) of the THPO gene. Functional studies showed that p.R119C
      affects not only ability of the cytokine to stimulate MPL but also its release,
      which is consistent with the relatively low serum THPO levels measured in
      patients. In all the three affected children, treatment with the THPO-mimetic
      romiplostim induced trilineage hematological responses, remission of bleeding and
      infections, and transfusion independence, which were maintained after up to 6.5
      years of observation. Recognizing patients with THPO mutations among those with
      juvenile bone marrow failure is essential to provide them with appropriate
      substitutive therapy and prevent the use of invasive and unnecessary treatments,
      such as hematopoietic stem cell transplantation or immunosuppression.

PMID- 29191946
TI  - Thrombopoietin: tickling the HSC's fancy.

PMID- 29191947
TI  - A proteomic network approach across the ALS-FTD disease spectrum resolves
      clinical phenotypes and genetic vulnerability in human brain.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are
      neurodegenerative diseases with overlap in clinical presentation, neuropathology,
      and genetic underpinnings. The molecular basis for the overlap of these disorders
      is not well established. We performed a comparative unbiased mass spectrometry
      based proteomic analysis of frontal cortical tissues from postmortem cases
      clinically defined as ALS, FTD, ALS and FTD (ALS/FTD), and controls. We also
      included a subset of patients with the C9orf72 expansion mutation, the most
      common genetic cause of both ALS and FTD Our systems-level analysis of the brain
      proteome integrated both differential expression and co-expression approaches to
      assess the relationship of these differences to clinical and pathological
      phenotypes. Weighted co-expression network analysis revealed 15 modules of co
      expressed proteins, eight of which were significantly different across the ALS
      FTD disease spectrum. These included modules associated with RNA binding
      proteins, synaptic transmission, and inflammation with cell-type specificity that
      showed correlation with TDP-43 pathology and cognitive dysfunction. Modules were
      also examined for their overlap with TDP-43 protein-protein interactions,
      revealing one module enriched with RNA-binding proteins and other causal ALS
      genes that increased in FTD/ALS and FTD cases. A module enriched with astrocyte
      and microglia proteins was significantly increased in ALS cases carrying the
      C9orf72 mutation compared to sporadic ALS cases, suggesting that the genetic
      expansion is associated with inflammation in the brain even without clinical
      evidence of dementia. Together, these findings highlight the utility of
      integrative systems-level proteomic approaches to resolve clinical phenotypes and
      genetic mechanisms underlying the ALS-FTD disease spectrum in human brain.

PMID- 29191949
TI  - Association of wheeze with lung function decline in children with sickle cell
      disease.

PMID- 29191950
TI  - Metabolic re-patterning in COPD airway smooth muscle cells.
AB  - Chronic obstructive pulmonary disease (COPD) airways are characterised by
      thickening of airway smooth muscle, partly due to airway smooth muscle cell
      (ASMC) hyperplasia. Metabolic reprogramming involving increased glycolysis and
      glutamine catabolism supports the biosynthetic and redox balance required for
      cellular growth. We examined whether COPD ASMCs show a distinct metabolic
      phenotype that may contribute to increased growth.We performed an exploratory
      intracellular metabolic profile analysis of ASMCs from healthy nonsmokers,
      healthy smokers and COPD patients, under unstimulated or growth conditions of
      transforming growth factor (TGF)-beta and fetal bovine serum (FBS).COPD ASMCs
      showed impaired energy balance and accumulation of the glycolytic product
      lactate, glutamine, fatty acids and amino acids compared to controls in
      unstimulated and growth conditions. Fatty acid oxidation capacity was reduced
      under unstimulated conditions. TGF-beta/FBS-stimulated COPD ASMCs showed
      restoration of fatty acid oxidation capacity, upregulation of the pentose
      phosphate pathway product ribose-5-phosphate and of nucleotide biosynthesis
      intermediates, and increased levels of the glutamine catabolite glutamate. In
      addition, TGF-beta/FBS-stimulated COPD ASMCs showed a higher reduced-to-oxidised
      glutathione ratio and lower mitochondrial oxidant levels. Inhibition of
      glycolysis and glutamine depletion attenuated TGF-beta/FBS-stimulated growth of
      COPD ASMCs.Changes in glycolysis, glutamine and fatty acid metabolism may lead to
      increased biosynthesis and redox balance, supporting COPD ASMC growth.

PMID- 29191951
TI  - Predictors of sleepiness in obstructive sleep apnoea at baseline and after 6
      months of continuous positive airway pressure therapy.
AB  - We evaluated factors associated with subjective and objective sleepiness at
      baseline and after 6 months of continuous positive airway pressure (CPAP) therapy
      in patients with obstructive sleep apnoea (OSA).We analysed data from the Apnoea
      Positive Pressure Long-term Efficacy Study (APPLES), a prospective 6-month
      multicentre randomised controlled trial with 1105 subjects with OSA, 558 of who
      were randomised to active CPAP. Epworth sleepiness scale (ESS) scores and the
      mean sleep latency (MSL) on the maintenance of wakefulness test at baseline and
      after 6 months of CPAP therapy were recorded.Excessive sleepiness (ESS score >10)
      was present in 543 (49.1%) participants. Younger age, presence of depression and
      higher apnoea-hypopnoea index were all associated with higher ESS scores and
      lower MSL. Randomisation to the CPAP group was associated with lower odds of
      sleepiness at 6 months. The prevalence of sleepiness was significantly lower in
      those using CPAP >4 h.night-1versus using CPAP <=4 h.night-1 Among those with
      good CPAP adherence, those with ESS >10 at baseline had significantly higher odds
      (OR 8.2, p<0.001) of persistent subjective sleepiness.Lower average nightly CPAP
      use and presence of sleepiness at baseline were independently associated with
      excessive subjective and objective sleepiness after 6 months of CPAP therapy.

PMID- 29191952
TI  - European Respiratory Society statement: diagnosis and treatment of pulmonary
      disease in alpha1-antitrypsin deficiency.
AB  - alpha1-antitrypsin deficiency (AATD) is the most common hereditary disorder in
      adults. It is associated with an increased risk of developing pulmonary emphysema
      and liver disease. The pulmonary emphysema in AATD is strongly linked to smoking,
      but even a proportion of never-smokers develop progressive lung disease. A large
      proportion of individuals affected remain undiagnosed and therefore without
      access to appropriate care and treatment.The most recent international statement
      on AATD was published by the American Thoracic Society and the European
      Respiratory Society in 2003. Since then there has been a continuous development
      of novel, more accurate and less expensive genetic diagnostic methods.
      Furthermore, new outcome parameters have been developed and validated for use in
      clinical trials and a new series of observational and randomised clinical trials
      have provided more evidence concerning the efficacy and safety of augmentation
      therapy, the only specific treatment available for the pulmonary disease
      associated with AATD.As AATD is a rare disease, it is crucial to organise
      national and international registries and collect information prospectively about
      the natural history of the disease. Management of AATD patients must be
      supervised by national or regional expert centres and inequalities in access to
      therapies across Europe should be addressed.

PMID- 29191954
TI  - The feasibility of a mandibular movement test as a screening tool for
      polysomnography candidates.

PMID- 29191953
TI  - Surfactant protein D is a causal risk factor for COPD: results of Mendelian
      randomisation.
AB  - Surfactant protein D (SP-D) is produced primarily in the lung and is involved in
      regulating pulmonary surfactants, lipid homeostasis and innate immunity.
      Circulating SP-D levels in blood are associated with chronic obstructive
      pulmonary disease (COPD), although causality remains elusive.In 4061 subjects
      with COPD, we identified genetic variants associated with serum SP-D levels. We
      then determined whether these variants affected lung tissue gene expression in
      1037 individuals. A Mendelian randomisation framework was then applied, whereby
      serum SP-D-associated variants were tested for association with COPD risk in 11
      157 cases and 36 699 controls and with 11 years decline of lung function in the
      4061 individuals.Three regions on chromosomes 6 (human leukocyte antigen region),
      10 (SFTPD gene) and 16 (ATP2C2 gene) were associated with serum SP-D levels at
      genome-wide significance. In Mendelian randomisation analyses, variants
      associated with increased serum SP-D levels decreased the risk of COPD (estimate 
      0.19, p=6.46*10-03) and slowed the lung function decline (estimate=0.0038,
      p=7.68*10-3).Leveraging genetic variation effect on protein, lung gene expression
      and disease phenotypes provided novel insights into SP-D biology and established
      a causal link between increased SP-D levels and protection against COPD risk and
      progression. SP-D represents a very promising biomarker and therapeutic target
      for COPD.

PMID- 29191955
TI  - Mortality: a neglected outcome in OCS-treated severe asthma.

PMID- 29191956
TI  - Genetic studies as a tool for identifying novel potential targets for treatment
      of COPD.

PMID- 29191958
TI  - The Art of Breathing: Apnoea.

PMID- 29191957
TI  - Reprogramming of cellular metabolism: driver for airway remodelling in COPD?

PMID- 29191959
TI  - Clinical Translation of Mesenchymal Stromal Cell Therapies in Nephrology.
AB  - Mesenchymal stromal cells have emerged as potential candidates for cell-based
      therapies to modulate the immune response in organ transplantation and repair
      tissues after acute or chronic injury. Preclinical studies have shown
      convincingly in rodent models that mesenchymal stromal cells can prolong solid
      organ graft survival and that they can induce immune tolerance, accelerate
      recovery from AKI, and promote functional improvement in chronic nephropathies.
      Multiple complex properties of the cells, including immunomodulatory, anti
      inflammatory, and proregenerative effects, seem to contribute. The promising
      preclinical studies have encouraged investigators to explore the safety,
      tolerability, and efficacy of mesenchymal stromal cell-based therapy in pilot
      clinical trials, including those for bone marrow and solid organ transplantation,
      autoimmune diseases, and tissue and organ repair. Here, we review the available
      data on culture-expanded mesenchymal stromal cells tested in renal
      transplantation, AKI, and CKD. We also briefly discuss the relevant issues that
      must be addressed to ensure rigorous assessment of the safety and efficacy of
      mesenchymal stromal cell therapies to allow the translation of this research into
      the practice of clinical nephrology.

PMID- 29191960
TI  - Magnesium and Risk of Hip Fracture among Patients Undergoing Hemodialysis.
AB  - Magnesium is an essential mineral for bone metabolism. However, little is known
      about the relationship between magnesium and the risk of fractures. In this
      cohort study, we elucidated the association between serum magnesium level and the
      risk of incident hip fracture among patients undergoing hemodialysis. We
      identified 113,683 patients undergoing hemodialysis with no history of hip
      fracture from a nation-wide database of patients undergoing dialysis in Japan.
      During a 2-year follow-up, a total of 2305 (2%) new hip fractures occurred. The
      crude incidence rate was significantly higher among patients in the lower
      quartiles of serum magnesium levels (2.63%, 2.08%, 1.76%, and 1.49% in Q1-Q4,
      respectively; P<0.001 for trend). The range of serum magnesium levels (in
      milligrams per deciliter) in each quartile was as follows: Q1, <2.3; Q2, 2.4-2.6;
      Q3, 2.7-2.8, and Q4, >2.9. After adjustment for demographic and clinical factors,
      patients in Q1 had a 1.23-fold higher risk for hip fracture than those in Q4 (95%
      confidence interval, 1.06 to 1.44; P<0.01). Similarly, an inverse probability
      weighting analysis showed an increased risk of hip fracture among patients in the
      lower magnesium quartiles. We did not observe significant effect modifications in
      subgroup analyses. The population-attributable fraction of serum magnesium level
      for incident hip fractures was 13.7% (95% confidence interval, 3.7% to 22.7%),
      which was much higher than that of serum calcium, serum phosphate, and
      parathyroid hormone levels. Thus, mild hypermagnesemia is associated with a lower
      risk of hip fracture among patients undergoing hemodialysis.

PMID- 29191961
TI  - Intragraft Molecular Pathways Associated with Tolerance Induction in Renal
      Transplantation.
AB  - The modern immunosuppression regimen has greatly improved short-term allograft
      outcomes but not long-term allograft survival. Complications associated with
      immunosuppression, specifically nephrotoxicity and infection risk, significantly
      affect graft and patient survival. Inducing and understanding pathways underlying
      clinical tolerance after transplantation are, therefore, necessary. We previously
      showed full donor chimerism and immunosuppression withdrawal in highly mismatched
      allograft recipients using a bioengineered stem cell product (FCRx). Here, we
      evaluated the gene expression and microRNA expression profiles in renal biopsy
      samples from tolerance-induced FCRx recipients, paired donor organs before
      implant, and subjects under standard immunosuppression (SIS) without rejection
      and with acute rejection. Unlike allograft samples showing acute rejection,
      samples from FCRx recipients did not show upregulation of T cell- and B cell
      mediated rejection pathways. Gene expression pathways differed slightly between
      FCRx samples and the paired preimplantation donor organ samples, but most of the
      functional gene networks overlapped. Notably, compared with SIS samples, FCRx
      samples showed upregulation of genes involved in pathways, like B cell receptor
      signaling. Additionally, prediction analysis showed inhibition of proinflammatory
      regulators and activation of anti-inflammatory pathways in FCRx samples.
      Furthermore, integrative analyses (microRNA and gene expression profiling from
      the same biopsy sample) identified the induction of regulators with demonstrated
      roles in the downregulation of inflammatory pathways and maintenance of tissue
      homeostasis in tolerance-induced FCRx samples compared with SIS samples. This
      pilot study highlights the utility of molecular intragraft evaluation of pathways
      related to FCRx-induced tolerance and the use of integrative analyses for
      identifying upstream regulators of the affected downstream molecular pathways.

PMID- 29191962
TI  - Nontypeable Haemophilus influenzae lysates increase heterogeneous nuclear
      ribonucleoprotein secretion and exosome release in human middle-ear epithelial
      cells.
AB  - Nontypeable Haemophilus influenzae (NTHi), one of the most common acute otitis
      media (OM) pathogens, is postulated to promote middle-ear epithelial remodeling
      in the progression of OM from acute to chronic. The goal of this study was to
      examine early quantitative proteomic secretome effects of NTHi lysate exposure in
      a human middle-ear epithelial cell (HMEEC) line. NTHi lysates were used to
      stimulate HMEEC, and conditional quantitative stable isotope labeling with amino
      acids in cell culture of cell secretions was performed. Mass spectrometry
      analysis identified 766 proteins across samples. Of interest, several
      heterogeneous nuclear ribonucleoproteins (hnRNPs) were regulated by NTHi lysate
      treatment, especially hnRNP A2B1 and hnRNP Q, known to be implicated in microRNA
      (miRNA) packaging in exosomes. After purification, the presence of exosomes in
      HMEEC secretions was characterized by dynamic light scattering (<100 nm),
      transmission electron microscopy, and CD63/heat shock protein 70 positivity.
      hnRNP A2B1 and hnRNP Q were confirmed to be found in exosomes by Western blot and
      proteomic analysis. Finally, exosomal miRNA content comprised 110 unique miRNAs,
      with 5 found to be statistically induced by NTHi lysate (miR-378a-3p + miR-378i,
      miR-200a-3p, miR-378g, miR30d-5p, and miR-222-3p), all known to target innate
      immunity genes. This study demonstrates that NTHi lysates promote release of
      miRNA-laden exosomes from middle-ear epithelium in vitro. -Val, S., Krueger, A.,
      Poley, M., Cohen, A., Brown, K., Panigrahi, A., Preciado, D. Nontypeable
      Haemophilus influenzae lysates increase heterogeneous nuclear ribonucleoprotein
      secretion and exosome release in human middle-ear epithelial cells.

PMID- 29191964
TI  - Women's Health Now, Yet So Far to Go.

PMID- 29191963
TI  - Competitive apnea and its effect on the human brain: focus on the redox
      regulation of blood-brain barrier permeability and neuronal-parenchymal
      integrity.
AB  - Static apnea provides a unique model that combines transient hypertension,
      hypercapnia, and severe hypoxemia. With apnea durations exceeding 5 min, the
      purpose of the present study was to determine how that affects cerebral free
      radical formation and the corresponding implications for brain structure and
      function. Measurements were obtained before and following a maximal apnea in 14
      divers with transcerebral exchange kinetics, measured as the product of global
      cerebral blood flow (duplex ultrasound) and radial arterial to internal jugular
      venous concentration differences ( a-vD). Apnea increased the systemic (arterial)
      and, to a greater extent, the regional (jugular venous) concentration of the
      ascorbate free radical, resulting in a shift from net cerebral uptake to output (
      P < 0.05). Peroxidation (lipid hydroperoxides, LDL oxidation), NO bioactivity,
      and S100beta were correspondingly enhanced ( P < 0.05), the latter interpreted as
      minor and not a pathologic disruption of the blood-brain barrier. However, those
      changes were insufficient to cause neuronal-parenchymal damage confirmed by the
      lack of change in the a-vD of neuron-specific enolase and human myelin basic
      protein ( P > 0.05). Collectively, these observations suggest that increased
      cerebral oxidative stress following prolonged apnea in trained divers may reflect
      a functional physiologic response, rather than a purely maladaptive phenomenon.
      Bain, A. R., Ainslie, P. N., Hoiland, R. L., Barak, O. F., Drvis, I., Stembridge,
      M., MacLeod, D. M., McEneny, J., Stacey, B. S., Tuaillon, E., Marchi, N., De
      Maudave, A. F., Dujic, Z., MacLeod, D. B., Bailey, D. M. Competitive apnea and
      its effect on the human brain: focus on the redox regulation of blood-brain
      barrier permeability and neuronal-parenchymal integrity.

PMID- 29191965
TI  - Caenorhabditis elegans models of tauopathy.
AB  - One of the hallmarks of the tauopathies, which include the neurodegenerative
      disorders, such as Alzheimer disease (AD), corticobasal degeneration,
      frontotemporal dementia, and progressive supranuclear palsy (PSP), is the
      abnormal accumulation of post-translationally modified, insoluble tau. The result
      is a loss of neurons, decreased mental function, and complete dependence of
      patients on others. Aggregation of tau, which under physiologic conditions is a
      highly soluble protein, is thought to be central to the pathogenesis of these
      diseases. Indeed one of the strongest lines of evidence is the MAPT gene
      polymorphisms that lead to the familial forms of tauopathy. Extensive research in
      animal models over the years has contributed some of the most important findings
      regarding the pathogenesis of these diseases. Despite this, the precise molecular
      mechanisms that lead to abnormal tau folding, accumulation, and spreading remain
      unknown. Owing to the fact that most of the biochemical pathways are conserved,
      Caenorhabditis elegans provides an alternative approach to identify cellular
      mechanisms and druggable genes that operate in such disorders. Many human genes
      implicated in neurodegenerative diseases have counterparts in C. elegans, making
      it an excellent model in which to study their pathogenesis. In this article, we
      review some of the important findings gained from C. elegans tauopathy models.
      Pir, G. J., Choudhary, B., Mandelkow, E. Caenorhabditiselegans models of
      tauopathy.

PMID- 29191967
TI  - Erratum.

PMID- 29191966
TI  - Erratum.

PMID- 29191968
TI  - Contextualising Safety in Numbers: a longitudinal investigation into change in
      cycling safety in Britain, 1991-2001 and 2001-2011.
AB  - INTRODUCTION: The 'Safety in Numbers' (SiN) phenomenon refers to a decline of
      injury risk per time or distance exposed as use of a mode increases. It has been
      demonstrated for cycling using cross-sectional data, but little evidence exists
      as to whether the effect applies longitudinally -that is, whether changes in
      cycling levels correlate with changes in per-cyclist injury risks. METHODS: This
      paper examines cross-sectional and longitudinal SiN effects in 202 local
      authorities in Britain, using commuting data from 1991, 2001 and 2011 censuses
      plus police -recorded data on 'killed and seriously injured' (KSI) road traffic
      injuries. We modelled a log-linear relationship between number of injuries and
      number of cycle commuters. Second, we conducted longitudinal analysis to examine
      whether local authorities where commuter cycling increased became safer (and vice
      versa). RESULTS: The paper finds a cross-sectional SiN effect exists in the 1991,
      2001 and 2011 censuses. The longitudinal analysis also found a SiN effect, that
      is, places where cycling increased were more likely to become safer than places
      where it had declined. Finally, these longitudinal results are placed in the
      context of changes in pedestrian, cyclist and motorist safety. While between 1991
      and 2001 all modes saw declines in KSI risk (37% for pedestrians, 36% for
      cyclists and 27% for motor vehicle users), between 2001 and 2011 pedestrians and
      motorists saw even more substantial declines (41% and 49%), while risk for
      cyclists increased by 4%. CONCLUSION: The SiN mechanism does seem to operate
      longitudinally as well as cross-sectionally. However, at a national level between
      2001-11 it co-existed with an increase in cyclist injury risk both in absolute
      terms and in relation to other modes.

PMID- 29191969
TI  - Olaratumab Exerts Antitumor Activity in Preclinical Models of Pediatric Bone and
      Soft Tissue Tumors through Inhibition of Platelet-Derived Growth Factor Receptor
      alpha.
AB  - Purpose: Platelet-derived growth factor receptor alpha (PDGFRalpha) is implicated
      in several adult and pediatric malignancies, where activated signaling in tumor
      cells and/or cells within the microenvironment drive tumorigenesis and disease
      progression. Olaratumab (LY3012207/IMC-3G3) is a human mAb that exclusively binds
      to PDGFRalpha and recently received accelerated FDA approval and conditional EMA
      approval for treatment of advanced adult sarcoma patients in combination with
      doxorubicin. In this study, we investigated olaratumab in preclinical models of
      pediatric bone and soft tissue tumors.Experimental Design: PDGFRalpha expression
      was evaluated by qPCR and Western blot analysis. Olaratumab was investigated in
      in vitro cell proliferation and invasion assays using pediatric osteosarcoma and
      rhabdoid tumor cell lines. In vivo activity of olaratumab was assessed in
      preclinical mouse models of pediatric osteosarcoma and malignant rhabdoid
      tumor.Results:In vitro olaratumab treatment of osteosarcoma and rhabdoid tumor
      cell lines reduced proliferation and inhibited invasion driven by individual
      platelet-derived growth factors (PDGFs) or serum. Furthermore, olaratumab delayed
      primary tumor growth in mouse models of pediatric osteosarcoma and malignant
      rhabdoid tumor, and this activity was enhanced by combination with either
      doxorubicin or cisplatin.Conclusions: Overall, these data indicate that
      olaratumab, alone and in combination with standard of care, blocks the growth of
      some preclinical PDGFRalpha-expressing pediatric bone and soft tissue tumor
      models. Clin Cancer Res; 24(4); 847-57. (c)2017 AACR.

PMID- 29191970
TI  - Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and
      Identifies Treatment-Resistant Clones in Neuroblastoma.
AB  - Purpose: Neuroblastoma displays important clinical and genetic heterogeneity,
      with emergence of new mutations at tumor progression.Experimental Design: To
      study clonal evolution during treatment and follow-up, an innovative method based
      on circulating cell-free DNA (cfDNA) analysis by whole-exome sequencing (WES)
      paired with target sequencing was realized in sequential liquid biopsy samples of
      19 neuroblastoma patients.Results: WES of the primary tumor and cfDNA at
      diagnosis showed overlap of single-nucleotide variants (SNV) and copy number
      alterations, with 41% and 93% of all detected alterations common to the primary
      neuroblastoma and cfDNA. CfDNA WES at a second time point indicated a mean of 22
      new SNVs for patients with progressive disease. Relapse-specific alterations
      included genes of the MAPK pathway and targeted the protein kinase A signaling
      pathway. Deep coverage target sequencing of intermediate time points during
      treatment and follow-up identified distinct subclones. For 17 seemingly relapse
      specific SNVs detected by cfDNA WES at relapse but not tumor or cfDNA WES at
      diagnosis, deep coverage target sequencing detected these alterations in minor
      subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell
      cycle. Furthermore a persisting, resistant clone with concomitant disappearance
      of other clones was identified by a mutation in the ubiquitin protein ligase
      HERC2Conclusions: Modelization of mutated allele fractions in cfDNA indicated
      distinct patterns of clonal evolution, with either a minor, treatment-resistant
      clone expanding to a major clone at relapse, or minor clones collaborating toward
      tumor progression. Identification of treatment-resistant clones will enable
      development of more efficient treatment strategies. Clin Cancer Res; 24(4); 939
      49. (c)2017 AACR.

PMID- 29191971
TI  - Surviving Ovarian Cancer: An Affair between Defective DNA Repair and RB1.
AB  - Detailed clinical and molecular evaluation of large cohorts of exceptional
      survivors provides an unprecedented opportunity to identify mechanisms underlying
      long-term survival that can drive future therapeutic approaches and biomarker
      development. Exceptional survivors of high-grade serous ovarian cancer
      demonstrate concurrent disruption of homologous recombination DNA repair and
      retinoblastoma protein. Clin Cancer Res; 24(3); 508-10. (c)2017 AACRSee related
      article by Garsed et al., p. 569.

PMID- 29191972
TI  - Mutations in Homologous Recombination Genes and Outcomes in Ovarian Carcinoma
      Patients in GOG 218: An NRG Oncology/Gynecologic Oncology Group Study.
AB  - Purpose: We hypothesized that mutations in homologous recombination repair (HRR)
      genes beyond BRCA1 and BRCA2 improve outcomes for ovarian carcinoma patients
      treated with platinum therapy and would impact the relative benefit of adding
      prolonged bevacizumab.Experimental Design: We sequenced DNA from blood and/or
      neoplasm from 1,195 women enrolled in GOG-0218, a randomized phase III trial in
      advanced ovarian carcinoma of bevacizumab added to carboplatin and paclitaxel.
      Defects in HRR were defined as damaging mutations in 16 genes. Proportional
      hazards models were used to estimate relative hazards for progression-free
      survival (PFS) and overall survival (OS).Results: Of 1,195 women with ovarian
      carcinoma, HRR mutations were identified in 307 (25.7%). Adjusted hazards for
      progression and death compared with those without mutations were lower for women
      with non-BRCA HRR mutations [HR = 0.73; 95% confidence interval (CI), 0.57-0.94;
      P = 0.01 for PFS; HR = 0.67; 95% CI, 0.50-0.90; P = 0.007 for OS] and BRCA1
      mutations (HR = 0.80; 95% CI, 0.66-0.97; P = 0.02 for PFS; HR = 0.74; 95% CI,
      0.59-0.94; P = 0.01 for OS) and were lowest for BRCA2 mutations (HR = 0.52; 95%
      CI, 0.40-0.67; P < 0.0001 for PFS; HR = 0.36; 95% CI, 0.25-0.53; P < 0.0001 for
      OS). A test of interaction showed no difference in the effect of bevacizumab on
      PFS between cases with and without mutations.Conclusions: HRR mutations,
      including non-BRCA genes, significantly prolong PFS and OS in ovarian carcinoma
      and should be stratified for in clinical trials. The benefit of adding
      bevacizumab was not significantly modified by mutation status. Clin Cancer Res;
      24(4); 777-83. (c)2017 AACR.

PMID- 29191973
TI  - Blocking the Feedback Loop between Neuroendocrine Differentiation and Macrophages
      Improves the Therapeutic Effects of Enzalutamide (MDV3100) on Prostate Cancer.
AB  - Purpose: Androgen deprivation therapy (ADT), including enzalutamide, induces
      resistance in prostate cancer; ADT resistance is associated with neuroendocrine
      differentiation (NED) and tumor-associated macrophages (TAM). This study aimed to
      investigate the association between enzalutamide-induced NED and TAMs and its
      mechanism.Experimental Design: The association between enzalutamide-induced NED
      and TAMs was investigated by IHC using prostate cancer tissues, enzalutamide
      resistant mouse xenografts, and a coculture system. The underlying mechanisms
      were assessed using in vitro cytokine antibody arrays, ELISAs, chromatin
      immunoprecipitation, and other methods. An orthotopic prostate cancer mouse model
      was established to evaluate the in vivo effects of combined IL6 receptor (IL6R)
      and high mobility group box 1 (HMGB1) inhibition on enzalutamide
      resistance.Results: High CD163 expression was observed in ADT-treated prostate
      cancer or castration-resistant prostate cancer (CRPC) tissues with high levels of
      neuron-specific enolase (NSE) and chromogranin A (CHGA) and in enzalutamide
      resistant xenografts, indicating the crucial roles of NED and TAMs in
      enzalutamide resistance. Specifically, enzalutamide-induced HMGB1 expression
      facilitated TAM recruitment and polarization and drove NED via beta-catenin
      stabilization. HMGB1-activated TAMs secreted IL6 to augment enzalutamide-induced
      NED and directly promote HMGB1 transcription via STAT3. Finally, inhibition of
      the IL6/STAT3 pathway by tocilizumab combined with HMGB1 knockdown inhibited
      enzalutamide-induced resistance in an orthotopic prostate cancer mouse
      model.Conclusions: Enzalutamide elevates HMGB1 levels, which recruits and
      activates TAMs. Moreover, IL6 secreted by HMGB1-activated TAMs facilitates the
      enzalutamide-induced NED of prostate cancer, forming a positive feedback loop
      between NED in prostate cancer and TAMs. The combined inhibition of IL6R and
      HMGB1 may serve as a new treatment for enzalutamide resistance in patients with
      advanced or metastatic prostate cancer. Clin Cancer Res; 24(3); 708-23. (c)2017
      AACR.

PMID- 29191974
TI  - First targeted therapy in multiple myeloma.

PMID- 29191975
TI  - The ecosystem of classical Hodgkin lymphoma.

PMID- 29191976
TI  - The unused iron.

PMID- 29191978
TI  - The Frankenthesis: This stitched-together monster is alive and coming to a campus
      near you.

PMID- 29191979
TI  - Shigella hijacks the glomulin-cIAPs-inflammasome axis to promote inflammation.
AB  - Shigella deploys a unique mechanism to manipulate macrophage pyroptosis by
      delivering the IpaH7.8 E3 ubiquitin ligase via its type III secretion system.
      IpaH7.8 ubiquitinates glomulin (GLMN) and elicits its degradation, thereby
      inducing inflammasome activation and pyroptotic cell death of macrophages. Here,
      we show that GLMN specifically binds cellular inhibitor of apoptosis proteins 1
      and 2 (cIAP1 and cIAP2), members of the inhibitor of apoptosis (IAP) family of
      RING-E3 ligases, which results in reduced E3 ligase activity, and consequently
      inflammasome-mediated death of macrophages. Importantly, reducing the levels of
      GLMN in macrophages via IpaH7.8, or siRNA-mediated knockdown, enhances
      inflammasome activation in response to infection by Shigella, Salmonella, or
      Pseudomonas, stimulation with NLRP3 inflammasome activators (including SiO2,
      alum, or MSU), or stimulation of the AIM2 inflammasome by poly dA:dT GLMN binds
      specifically to the RING domain of both cIAPs, which inhibits their self
      ubiquitination activity. These findings suggest that GLMN is a negative regulator
      of cIAP-mediated inflammasome activation, and highlight a unique Shigella
      stratagem to kill macrophages, promoting severe inflammation.

PMID- 29191980
TI  - Prior automatic posture and activity identification improves physical activity
      energy expenditure prediction from hip-worn triaxial accelerometry.
AB  - Accelerometry is increasingly used to quantify physical activity (PA) and related
      energy expenditure (EE). Linear regression models designed to derive PAEE from
      accelerometry-counts have shown their limits, mostly due to the lack of
      consideration of the nature of activities performed. Here we tested whether a
      model coupling an automatic activity/posture recognition (AAR) algorithm with an
      activity-specific count-based model, developed in 61 subjects in laboratory
      conditions, improved PAEE and total EE (TEE) predictions from a hip-worn triaxial
      accelerometer (ActigraphGT3X+) in free-living conditions. Data from two
      independent subject groups of varying body mass index and age were considered: 20
      subjects engaged in a 3-h urban-circuit, with activity-by-activity reference PAEE
      from combined heart-rate and accelerometry monitoring (Actiheart); and 56
      subjects involved in a 14-day trial, with PAEE and TEE measured using the doubly
      labeled water method. PAEE was estimated from accelerometry using the activity
      specific model coupled to the AAR algorithm (AAR model), a simple linear model
      (SLM), and equations provided by the companion-software of used activity-devices
      (Freedson and Actiheart models). AAR-model predictions were in closer agreement
      with selected references than those from other count-based models, both for PAEE
      during the urban-circuit (RMSE = 6.19 vs 7.90 for SLM and 9.62 kJ/min for
      Freedson) and for EE over the 14-day trial, reaching Actiheart performances in
      the latter (PAEE: RMSE = 0.93 vs. 1.53 for SLM, 1.43 for Freedson, 0.91 MJ/day
      for Actiheart; TEE: RMSE = 1.05 vs. 1.57 for SLM, 1.70 for Freedson, 0.95 MJ/day
      for Actiheart). Overall, the AAR model resulted in a 43% increase of daily PAEE
      variance explained by accelerometry predictions. NEW & NOTEWORTHY Although
      triaxial accelerometry is widely used in free-living conditions to assess the
      impact of physical activity energy expenditure (PAEE) on health, its precision
      and accuracy are often debated. Here we developed and validated an activity
      specific model which, coupled with an automatic activity-recognition algorithm,
      improved the variance explained by the predictions from accelerometry counts by
      43% of daily PAEE compared with models relying on a simple relationship between
      accelerometry counts and EE.

PMID- 29191977
TI  - The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting
      Deadpan and Zelda.
AB  - The TRIM-NHL protein Brain tumor (Brat) acts as a tumor suppressor in the
      Drosophila brain, but how it suppresses tumor formation is not completely
      understood. Here, we combine temperature-controlled brat RNAi with transcriptome
      analysis to identify the immediate Brat targets in Drosophila neuroblasts.
      Besides the known target Deadpan (Dpn), our experiments identify the
      transcription factor Zelda (Zld) as a critical target of Brat. Our data show that
      Zld is expressed in neuroblasts and required to allow re-expression of Dpn in
      transit-amplifying intermediate neural progenitors. Upon neuroblast division,
      Brat is enriched in one daughter cell where its NHL domain directly binds to
      specific motifs in the 3'UTR of dpn and zld mRNA to mediate their degradation. In
      brat mutants, both Dpn and Zld continue to be expressed, but inhibition of either
      transcription factor prevents tumorigenesis. Our genetic and biochemical data
      indicate that Dpn inhibition requires higher Brat levels than Zld inhibition and
      suggest a model where stepwise post-transcriptional inhibition of distinct
      factors ensures sequential generation of fates in a stem cell lineage.

PMID- 29191981
TI  - Impact of training state on fasting-induced regulation of adipose tissue
      metabolism in humans.
AB  - Recruitment of fatty acids from adipose tissue is increased during fasting.
      However, the molecular mechanisms behind fasting-induced metabolic regulation in
      human adipose tissue and the potential impact of training state in this are
      unknown. Therefore the aim of the present study was to investigate 1) fasting
      induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as
      well as 2) the impact of training state on basal oxidative capacity and fasting
      induced metabolic regulation in human adipose tissue. Untrained [maximal oxygen
      uptake (Vo2max) < 45 ml.min-1.kg-1] and trained subjects (Vo2max > 55 ml.min-1.kg
      1) fasted for 36 h, and abdominal subcutaneous adipose tissue biopsies were
      obtained 2, 12, 24, and 36 h after a standardized meal. Adipose tissue oxidative
      phosphorylation complexes, phosphoenolpyruvate carboxykinase, and pyruvate
      dehydrogenase (PDH)-E1alpha protein as well as PDH kinase (PDK) 2, PDK4, and PDH
      phosphatase 2 mRNA content were higher in trained subjects than in untrained
      subjects. In addition, trained subjects had higher adipose tissue hormone
      sensitive lipase Ser660 phosphorylation and adipose triglyceride lipase protein
      content as well as higher plasma free fatty acid concentration than untrained
      subjects during fasting. Moreover, adipose tissue PDH phosphorylation increased
      with fasting only in trained subjects. Taken together, trained subjects seem to
      possess higher basal adipose tissue oxidative capacity as well as higher capacity
      for regulation of lipolysis and for providing substrate for glyceroneogenesis in
      adipose tissue during fasting than untrained subjects. NEW & NOTEWORTHY This
      study shows for the first time higher protein content of lipolytic enzymes and
      higher oxidative phosphorylation protein in adipose tissue from trained subjects
      than from untrained subjects during fasting. Furthermore, trained subjects had
      higher capacity for adipose tissue glyceroneogenesis than untrained subjects.

PMID- 29191982
TI  - Exercise-induced diaphragm fatigue in a Paralympic champion rower with spinal
      cord injury.
AB  - The aim of this case report was to determine whether maximal upper body exercise
      was sufficient to induce diaphragm fatigue in a Paralympic champion adaptive
      rower with low-lesion spinal cord injury (SCI). An elite arms-only oarsman (age:
      28 yr; stature: 1.89 m; and mass: 90.4 kg) with motor-complete SCI (T12)
      performed a 1,000-m time trial on an adapted rowing ergometer. Exercise
      measurements comprised pulmonary ventilation and gas exchange, diaphragm EMG
      derived indexes of neural respiratory drive, and intrathoracic pressure-derived
      indexes of respiratory mechanics. Diaphragm fatigue was assessed by measuring pre
      to postexercise changes in the twitch transdiaphragmatic pressure (Pdi,tw)
      response to anterolateral magnetic stimulation of the phrenic nerves. The time
      trial (248 +/- 25 W, 3.9 min) elicited a peak O2 uptake of 3.46 l/min and a peak
      pulmonary ventilation of 150 l/min (57% MVV). Breath-to-stroke ratio was 1:1
      during the initial 400 m and 2:1 thereafter. The ratio of inspiratory
      transdiaphragmatic pressure to diaphragm EMG (neuromuscular efficiency) fell from
      rest to 600 m (16.0 vs. 3.0). Potentiated Pdi,tw was substantially reduced (-33%)
      at 15-20 min postexercise, with only partial recovery (-12%) at 30-35 min. This
      is the first report of exercise-induced diaphragm fatigue in SCI. The decrease in
      diaphragm neuromuscular efficiency during exercise suggests that the fatigue was
      partly due to factors independent of ventilation (e.g., posture and locomotion).
      NEW & NOTEWORTHY This case report provides the first objective evidence of
      exercise-induced diaphragm fatigue in spinal cord injury (SCI) and, for that
      matter, in any population undertaking upper body exercise. Our data support the
      notion that high levels of exercise hyperpnea and factors other than ventilation
      (e.g., posture and locomotion) are responsible for the fatigue noted after upper
      body exercise. The findings extend our understanding of the limits of
      physiological function in SCI.

PMID- 29191983
TI  - Alteration in upper airway dilator muscle coactivation during sleep: comparison
      of patients with obstructive sleep apnea and healthy subjects.
AB  - In patients with obstructive sleep apnea (OSA), substantial increases in
      genioglossus (GG) activity during hypopneas/apneas usually fail to restore normal
      airflow. We have previously suggested that sleep-induced alteration in tongue
      muscle coordination may explain this finding, as retractor muscle coactivation
      was reduced during sleep compared with wakefulness. The present study was
      undertaken to evaluate whether these alterations in dilator muscle activation
      during sleep play a role in the pathogenesis of OSA and whether coactivation of
      additional peripharyngeal muscles (non-GG muscles: styloglossus, geniohyoid,
      sternohyoid, and sternocleidomastoid) is also impaired during sleep. We compared
      GG and non-GG muscle electromyographic (EMG) activity in 8 patients with OSA and
      12 healthy subjects during wakefulness while breathing through inspiratory
      resistors with the activity observed during sleep toward the end of flow
      limitation, before arousal, at equivalent esophageal pressures. During
      wakefulness, resistive breathing triggered increases in both GG and non-GG muscle
      activity. During sleep, flow limitation was associated with increases in GG-EMG
      that reached, on average, >2-fold the level observed while awake. In contrast,
      EMGs of the non-GG muscles, recorded simultaneously, reached, on average, only
      ~2/3 the wakefulness level. We conclude that during sleep GG activity may
      increase to levels that substantially exceed those sufficient to prevent
      pharyngeal collapse during wakefulness, whereas other peripharyngeal muscles do
      not coactivate during sleep in both patients with OSA and healthy subjects. We
      speculate that upper airway muscle dyssynchrony during sleep may explain why GG
      EMG activation fails to alleviate flow limitation and stabilize airway patency
      during sleep. NEW & NOTEWORTHY Pharyngeal obstruction during sleep may trigger
      genioglossus activity to levels substantially exceeding those observed during
      wakefulness, without ameliorating flow limitation. In contrast, other
      peripharyngeal muscles exhibit a much lower activity during sleep in both
      patients with obstructive sleep apnea and healthy subjects. Coordinated muscular
      synergy stabilizes the pharynx despite relatively low activity while awake, yet
      even higher genioglossal activity allows the pharynx to obstruct when
      simultaneous activity of other dilator muscles is inadequate during sleep.

PMID- 29191984
TI  - Correction for Kim et al., "Hepatitis C Virus Impairs Natural Killer Cell
      Mediated Augmentation of Complement Synthesis".

PMID- 29191985
TI  - Reply to "Bioinformatics Analysis of Differential Innate Immune Signaling in
      Macrophages by Wild-Type Vaccinia Mature Virus and a Mutant Virus with a Deletion
      of the A26 Protein".

PMID- 29191986
TI  - Correction for Yang et al., "Neglected but Important Role of Apolipoprotein E
      Exchange in Hepatitis C Virus Infection".

PMID- 29191987
TI  - Correction for Kwei et al., "Impaired Virion Secretion by Hepatitis B Virus
      Immune Escape Mutants and Its Rescue by Wild-Type Envelope Proteins or a Second
      Site Mutation".

PMID- 29191988
TI  - Classic Spotlight, 2014 and 2015: Articles of Significant Interest Selected from
      the Journal of Virology Archives by the Editors.

PMID- 29191989
TI  - Retraction for Subba-Reddy et al., "Norovirus RNA Synthesis Is Modulated by an
      Interaction between the Viral RNA-Dependent RNA Polymerase and the Major Capsid
      Protein, VP1".

PMID- 29191990
TI  - Correction for Fricke et al., "Human Cytosolic Extracts Stabilize the HIV-1
      Core".

PMID- 29191991
TI  - Bioinformatics Analysis of Differential Innate Immune Signaling in Macrophages by
      Wild-Type Vaccinia Mature Virus and a Mutant Virus with a Deletion of the A26
      Protein.

PMID- 29191992
TI  - Recognizing the Top 25 Peer Reviewers for the Journal of Virology.

PMID- 29191993
TI  - Acknowledgment of Ad Hoc Reviewers.

PMID- 29191994
TI  - Correction for Cousins and Nicholas, "Role of Human Herpesvirus 8 Interleukin-6
      Activated gp130 Signal Transducer in Primary Effusion Lymphoma Cell Growth and
      Viability".

PMID- 29191995
TI  - Help and hindrance: continuous glucose monitors and contact allergy.

PMID- 29191996
TI  - Question 1: Does zinc enhance recovery time from gastroenteritis in high-income
      countries?

PMID- 29191997
TI  - The reality of FGM in the UK.

PMID- 29191998
TI  - Question 2: Is the packed cell volume / 3 rule valid for estimating haemoglobin
      in children in malarious areas?

PMID- 29191999
TI  - Question 1: Are topical or oral antibiotics best for treating tympanostomy tube
      otorrhoea?

PMID- 29192000
TI  - Drooling Reduction Intervention randomised trial (DRI): comparing the efficacy
      and acceptability of hyoscine patches and glycopyrronium liquid on drooling in
      children with neurodisability.
AB  - OBJECTIVE: Investigate whether hyoscine patch or glycopyrronium liquid is more
      effective and acceptable to treat drooling in children with neurodisability.
      DESIGN: Multicentre, single-blind, randomised controlled trial. SETTING:
      Recruitment through neurodisability teams; treatment by parents. PARTICIPANTS:
      Ninety children with neurodisability who had never received medication for
      drooling (55 boys, 35 girls; median age 4 years). EXCLUSION CRITERIA: medication
      contraindicated; in a trial that could affect drooling or management.
      INTERVENTION: Children were randomised to receive a hyoscine skin patch or
      glycopyrronium liquid. Dose was increased over 4 weeks to achieve optimum symptom
      control with minimal side-effects; steady dose then continued to 12 weeks.
      PRIMARY AND SECONDARY OUTCOMES: Primary outcome: Drooling Impact Scale (DIS)
      score at week-4. SECONDARY OUTCOMES: change in DIS scores over 12 weeks, Drooling
      Severity and Frequency Scale and Treatment Satisfaction Questionnaire for
      Medication; adverse events; children's perception about treatment. RESULTS: Both
      medications yielded clinically and statistically significant reductions in mean
      DIS at week-4 (25.0 (SD 22.2) for hyoscine and 26.6 (SD 16) for glycopyrronium).
      There was no significant difference in change in DIS scores between treatment
      groups. By week-12, 26/47 (55%) children starting treatment were receiving
      hyoscine compared with 31/38 (82%) on glycopyrronium. There was a 42% increased
      chance of being on treatment at week-12 for children randomised to glycopyrronium
      relative to hyoscine (1.42, 95% CI 1.04 to 1.95). CONCLUSIONS: Hyoscine and
      glycopyrronium are clinically effective in treating drooling in children with
      neurodisability. Hyoscine produced more problematic side effects leading to a
      greater chance of treatment cessation. TRIAL REGISTRATION NUMBERS: ISRCTN
      75287237; EUDRACT: 2013-000863-94; Medicines and Healthcare Products Regulatory
      Agency: 17136/0264/001-0003.

PMID- 29192001
TI  - A child with nail changes.

PMID- 29192003
TI  - RE: Statistical Interpretation Error in Metformin Trial Article.

PMID- 29192002
TI  - MS Western, a Method of Multiplexed Absolute Protein Quantification is a
      Practical Alternative to Western Blotting.
AB  - Absolute quantification of proteins elucidates the molecular composition,
      regulation and dynamics of multiprotein assemblies and networks. Here we report
      on a method termed MS Western that accurately determines the molar abundance of
      dozens of user-selected proteins at the subfemtomole level in whole cell or
      tissue lysates without metabolic or chemical labeling and without using specific
      antibodies. MS Western relies on GeLC-MS/MS and quantifies proteins by in-gel
      codigestion with an isotopically labeled QconCAT protein chimera composed of
      concatenated proteotypic peptides. It requires no purification of the chimera and
      relates the molar abundance of all proteotypic peptides to a single reference
      protein. In comparative experiments, MS Western outperformed immunofluorescence
      Western blotting by the protein detection specificity, linear dynamic range and
      sensitivity of protein quantification. To validate MS Western in an in vivo
      experiment, we quantified the molar content of zebrafish core histones H2A, H2B,
      H3 and H4 during ten stages of early embryogenesis. Accurate quantification
      (CV<10%) corroborated the anticipated histones equimolar stoichiometry and
      revealed an unexpected trend in their total abundance.

PMID- 29192004
TI  - Effectiveness of a Comprehensive Case Management Service for Children With
      Medical Complexity.
AB  - OBJECTIVES: To assess whether children with medical complexity (CMC) exposed to a
      hospital-based comprehensive case management service (CCMS) experience improved
      health care quality, improved functional status, reduced hospital-based
      utilization, and/or reduced overall health care costs. METHODS: Eligible CMC at
      Seattle Children's Hospital were enrolled in a cluster randomized controlled
      trial between December 1, 2010, and September 29, 2014. Participating primary
      care providers (PCPs) were randomly assigned, and CMC either had access to an
      outpatient hospital-based CCMS or usual care directed by their PCP. The CCMS
      included visits to a multidisciplinary clinic >= every 6 months for 1.5 years, an
      individualized shared care plan, and access to CCMS providers. Differences
      between control and intervention groups in change from baseline to 12 months and
      baseline to 18 months (difference of differences) were tested. RESULTS: Two
      hundred PCPs caring for 331 CMC were randomly assigned. Intervention group (n =
      181) parents reported more improvement in the Consumer Assessment of Healthcare
      Providers and Systems version 4.0 Child Health Plan Survey global health care
      quality ratings than control group parents (6.7 [95% confidence interval (CI):
      3.5-9.8] vs 1.3 [95% CI: 1.9-4.6] at 12 months). We did not detect significant
      differences in child functional status and most hospital-based utilization
      between groups. The difference in change of overall health care costs was higher
      in the intervention group (+$8233 [95% CI: $1701-$16 937]) at 18 months). CCMS
      clinic costs averaged $3847 per child-year. CONCLUSIONS: Access to a CCMS
      generally improved health care quality, but was not associated with changes in
      child functional status or hospital-based utilization, and increased overall
      health care costs among CMC.

PMID- 29192005
TI  - Successful Reversal of Furosemide-Induced Secondary Hyperparathyroidism With
      Cinacalcet.
AB  - Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy
      that can occur in patients treated with the loop diuretic for a long period of
      time. We report a 6-month-old 28-weeks premature infant treated chronically with
      furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and
      severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic
      and the addition of supplemental calcium and calcitriol only partially reversed
      the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL.
      After introduction of the calcimimetic Cinacalcet, we observed a sustained
      normalization of parathyroid hormone concentration at 27 to 63 pg/mL and, with
      that correction, of all biochemical abnormalities and healing of the bone
      disease. No adverse effects were noted. We conclude that in cases of SHPT due to
      furosemide in which traditional treatment fails, there may be room to consider
      the addition of a calcimimetic agent.

PMID- 29192006
TI  - Re: Confusing Recommendations Regarding Timing of Peanut-Based Foods to Low-risk
      Infants.

PMID- 29192008
TI  - Pastor-Villaescusa B, Canete MD, Caballero-Villarraso J, et al. Metformin for
      Obesity in Prepubertal and Pubertal Children: A Randomized Controlled Trial.
      Pediatrics. 2017;140(1):e20164285.

PMID- 29192007
TI  - Care Management for Children With Medical Complexity: Integration Is Essential.

PMID- 29192009
TI  - Authors' Response.

PMID- 29192011
TI  - Flynn JT, Kaelber DC, Baker-Smith CM, et al; SUBCOMMITTEE ON SCREENING AND
      MANAGEMENT OF HIGH BLOOD PRESSURE IN CHILDREN. Clinical Practice Guideline for
      Screening and Management of High Blood Pressure in Children and Adolescents.
      Pediatrics. 2017; 140(3):e20171904.

PMID- 29192010
TI  - Authors' Response.

PMID- 29192012
TI  - Brief guide to the analysis, interpretation and presentation of microbiota data.

PMID- 29192013
TI  - Cost savings from simple interventions to reduce unnecessary urinary
      investigations.

PMID- 29192014
TI  - Postnatal contraception discontinuation: different methods, same problem.

PMID- 29192015
TI  - EMA Review of Panobinostat (Farydak) for the Treatment of Adult Patients with
      Relapsed and/or Refractory Multiple Myeloma.
AB  - : On August 28, 2015, a marketing authorization valid through the European Union
      was issued for panobinostat, in combination with bortezomib and dexamethasone,
      for the treatment of adult patients with relapsed and/or refractory multiple
      myeloma who have received at least two prior regimens including bortezomib and an
      immunomodulatory agent (IMiD).Panobinostat is an orally available histone
      deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC
      proteins at nanomolar concentrations. HDAC proteins catalyze the removal of
      acetyl groups from the lysine residues of histones and some nonhistone proteins.
      Inhibition of HDAC activity results in increased acetylation of histone proteins,
      an epigenetic alteration that results in a relaxing of chromatin, leading to
      transcriptional activation. The recommended starting dose of panobinostat is 20
      mg, taken orally in a cyclical manner for up to 48 weeks.The use of panobinostat
      in combination with bortezomib and dexamethasone was studied in a randomized,
      double-blind, placebo-controlled, multicenter phase III study (PANORAMA I) in 768
      patients with relapsed or relapsed and refractory multiple myeloma who had
      received one to three prior lines of therapies. In the subgroup of patients who
      have received at least two prior regimens including bortezomib and an IMiD, there
      was a difference of 7.8 months in the progression-free survival in favor of the
      experimental arm (12.5 months for panobinostat + bortezomib + dexamethasone vs.
      4.7 months for placebo + bortezomib + dexamethasone; hazard ratio = 0.47, 95%
      confidence interal 0.31-0.72; log-rank p value = .0003). The incidence of grade 3
      4 adverse events suspected to be related to study drug was 76.9% vs. 51.2%, for
      the panobinostat and the placebo group, respectively. The most common side
      effects (grade 3-4) associated with panobinostat included diarrhea (18.9%),
      fatigue (14.7%), nausea (4.5%), vomiting (5.5%), thrombocytopenia (43.6%), anemia
      (7.9%), neutropenia (16.5%) and lymphopenia (8.1%).This article summarizes the
      scientific review of the application leading to regulatory approval in the
      European Union. The full scientific assessment report and product information,
      including the Summary of Product Characteristics, are available on the European
      Medicines Agency website
      (http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_l
      nding_page.jsp&mid=). IMPLICATIONS FOR PRACTICE: Farydak was approved in the
      European Union in combination with bortezomib and dexamethasone, for the
      treatment of adult patients with relapsed and/or refractory multiple myeloma who
      have received at least two prior regimens including bortezomib and an
      immunomodulatory agent (IMiD). The addition of panobinostat to bortezomib and
      dexamethasone resulted in a clinically meaningful and statistically significant
      improvement of progression-free survival compared with bortezomib and
      dexamethasone, and an additional therapeutic option with a new mechanism of
      action was considered valuable. Although the toxicity associated with
      panobinostat combination was significant, at the time of the marketing
      authorization of panobinostat, it was considered that it was acceptable and that
      it should be left to the clinician and the patient to decide whether the
      panobinostat combination is the preferred treatment option or not.

PMID- 29192016
TI  - Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose
      Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect
      Comparison.
AB  - BACKGROUND: Daratumumab (a human CD38-directed monoclonal antibody) and
      pomalidomide (an immunomodulatory drug) plus dexamethasone are both relatively
      new treatment options for patients with heavily pretreated multiple myeloma. A
      matching adjusted indirect comparison (MAIC) was used to compare absolute
      treatment effects of daratumumab versus pomalidomide + low-dose dexamethasone
      (LoDex; 40 mg) on overall survival (OS), while adjusting for differences between
      the trial populations. MATERIALS AND METHODS: The MAIC method reduces the risk of
      bias associated with naive indirect comparisons. Data from 148 patients receiving
      daratumumab (16 mg/kg), pooled from the GEN501 and SIRIUS studies, were compared
      separately with data from patients receiving pomalidomide + LoDex in the MM-003
      and STRATUS studies. RESULTS: The MAIC-adjusted hazard ratio (HR) for OS of
      daratumumab versus pomalidomide + LoDex was 0.56 (95% confidence interval [CI],
      0.38-0.83; p = .0041) for MM-003 and 0.51 (95% CI, 0.37-0.69; p < .0001) for
      STRATUS. The treatment benefit was even more pronounced when the daratumumab
      population was restricted to pomalidomide-naive patients (MM-003: HR, 0.33; 95%
      CI, 0.17-0.66; p = .0017; STRATUS: HR, 0.41; 95% CI, 0.21-0.79; p = .0082). An
      additional analysis indicated a consistent trend of the OS benefit across
      subgroups based on M-protein level reduction (>=50%, >=25%, and <25%).
      CONCLUSION: The MAIC results suggest that daratumumab improves OS compared with
      pomalidomide + LoDex in patients with heavily pretreated multiple myeloma.
      IMPLICATIONS FOR PRACTICE: This matching adjusted indirect comparison of clinical
      trial data from four studies analyzes the survival outcomes of patients with
      heavily pretreated, relapsed/refractory multiple myeloma who received either
      daratumumab monotherapy or pomalidomide plus low-dose dexamethasone. Using this
      method, daratumumab conferred a significant overall survival benefit compared
      with pomalidomide plus low-dose dexamethasone. In the absence of head-to-head
      trials, these indirect comparisons provide useful insights to clinicians and
      reimbursement authorities around the relative efficacy of treatments.

PMID- 29192017
TI  - Immunotherapy for Head and Neck Cancer in the Era of Exponentially Increasing
      Health Care Expenditure.

PMID- 29192018
TI  - High-Dose Mitotane-Induced Encephalopathy in the Treatment of Adrenocortical
      Carcinoma.

PMID- 29192019
TI  - Pre- and Postoperative Chemotherapy in Localized Extremity Soft Tissue Sarcoma: A
      European Organization for Research and Treatment of Cancer Expert Survey.
AB  - BACKGROUND: The management of localized extremity soft tissue sarcomas (STS) is
      challenging and the role of pre- and postoperative chemotherapy is unclear and
      debated among experts. MATERIALS AND METHODS: Medical oncology experts of the
      European Organization for Research and Treatment of Cancer Soft Tissue and Bone
      Sarcoma Group were asked to participate in this survey on the use of pre- and
      postoperative chemotherapy in STS. Experts from 12 centers in Belgium, France,
      Germany, Great Britain, Italy, Switzerland, and The Netherlands agreed to
      participate and provided their treatment algorithm. Answers were converted into
      decision trees based on the objective consensus methodology. The decision trees
      were used as a basis to identify consensus and discrepancies. RESULTS: Several
      criteria used for decision-making in extremity STS were identified:
      chemosensitivity, fitness, grading, location, and size. In addition,
      resectability and resection status were relevant in the pre- and postoperative
      setting, respectively. Preoperative chemotherapy is considered in most centers
      for marginally resectable tumors only. Yet, in some centers, neoadjuvant
      chemotherapy is used routinely and partially combined with hyperthermia. Although
      most centers do not recommend postoperative chemotherapy, some offer this
      treatment on a regular basis. Radiotherapy is an undisputed treatment modality in
      extremity STS. CONCLUSION: Due to lacking evidence on the utility of pre- and
      postoperative chemotherapy in localized extremity STS, treatment strategies vary
      considerably among European experts. The majority recommended neoadjuvant
      chemotherapy for marginally resectable grade 2-3 tumors; the majority did not
      recommend postoperative chemotherapy in any setting. IMPLICATIONS FOR PRACTICE:
      The management of localized extremity soft tissue sarcomas (STS) is challenging
      and the role of pre- and postoperative chemotherapy is unclear and debated among
      experts. This study analyzed the decision-making process among 12 European
      experts on systemic therapy for STS. A wide range of recommendations among
      experts regarding the use of perioperative chemotherapy was discovered.
      Discrepancies in the use of decision criteria were also uncovered, including the
      definition of what constitutes high-risk cancer, which is a basis for many to
      recommend chemotherapy. Before any standardization is possible, a common use of
      decision criteria is necessary.

PMID- 29192020
TI  - Sexual health services on the brink.

PMID- 29192022
TI  - Photochemistry of highly excited states.

PMID- 29192021
TI  - Contributions of primate prefrontal cortex and medial temporal lobe to temporal
      order memory.
AB  - Neuropsychological and neurophysiological studies have emphasized the role of the
      prefrontal cortex (PFC) in maintaining information about the temporal order of
      events or items for upcoming actions. However, the medial temporal lobe (MTL) has
      also been considered critical to bind individual events or items to their
      temporal context in episodic memory. Here we characterize the contributions of
      these brain areas by comparing single-unit activity in the dorsal and ventral
      regions of macaque lateral PFC (d-PFC and v-PFC) with activity in MTL areas
      including the hippocampus (HPC), entorhinal cortex, and perirhinal cortex (PRC)
      as well as in area TE during the encoding phase of a temporal-order memory task.
      The v-PFC cells signaled specific items at particular time periods of the task.
      By contrast, MTL cortical cells signaled specific items across multiple time
      periods and discriminated the items between time periods by modulating their
      firing rates. Analysis of the temporal dynamics of these signals showed that the
      conjunctive signal of item and temporal-order information in PRC developed
      earlier than that seen in v-PFC. During the delay interval between the two cue
      stimuli, while v-PFC provided prominent stimulus-selective delay activity, MTL
      areas did not. Both regions of PFC and HPC exhibited an incremental timing signal
      that appeared to represent the continuous passage of time during the encoding
      phase. However, the incremental timing signal in HPC was more prominent than that
      observed in PFC. These results suggest that PFC and MTL contribute to the
      encoding of the integration of item and timing information in distinct ways.

PMID- 29192023
TI  - Galphas protein binds ubiquitin to regulate epidermal growth factor receptor
      endosomal sorting.
AB  - The Galphas subunit is classically involved in the signal transduction of G
      protein-coupled receptors (GPCRs) at the plasma membrane. Recent evidence has
      revealed noncanonical roles for Galphas in endosomal sorting of receptors to
      lysosomes. However, the mechanism of action of Galphas in this sorting step is
      still poorly characterized. Here, we report that Galphas interacts with ubiquitin
      to regulate the endosomal sorting of receptors for lysosomal degradation. We
      reveal that the N-terminal extremity of Galphas contains a ubiquitin-interacting
      motif (UIM), a sorting element usually found in the endosomal sorting complex
      required for transport (ESCRT) machinery responsible for sorting ubiquitinated
      receptors into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs).
      Mutation of the UIM in Galphas confirmed the importance of ubiquitin interaction
      for the sorting of epidermal growth factor receptor (EGFR) into ILVs for
      lysosomal degradation. These findings demonstrate a role for Galphas as an
      integral component of the ubiquitin-dependent endosomal sorting machinery and
      highlight the dual role of Galphas in receptor trafficking and signaling for the
      fine-tuning of the cellular response.

PMID- 29192024
TI  - Eph-ephrin signaling modulated by polymerization and condensation of receptors.
AB  - Eph receptor signaling plays key roles in vertebrate tissue boundary formation,
      axonal pathfinding, and stem cell regeneration by steering cells to positions
      defined by its ligand ephrin. Some of the key events in Eph-ephrin signaling are
      understood: ephrin binding triggers the clustering of the Eph receptor, fostering
      transphosphorylation and signal transduction into the cell. However, a
      quantitative and mechanistic understanding of how the signal is processed by the
      recipient cell into precise and proportional responses is largely lacking.
      Studying Eph activation kinetics requires spatiotemporal data on the number and
      distribution of receptor oligomers, which is beyond the quantitative power
      offered by prevalent imaging methods. Here we describe an enhanced fluorescence
      fluctuation imaging analysis, which employs statistical resampling to measure the
      Eph receptor aggregation distribution within each pixel of an image. By
      performing this analysis over time courses extending tens of minutes, the
      information-rich 4D space (x, y, oligomerization, time) results were coupled to
      straightforward biophysical models of protein aggregation. This analysis reveals
      that Eph clustering can be explained by the combined contribution of
      polymerization of receptors into clusters, followed by their condensation into
      far larger aggregates. The modeling reveals that these two competing
      oligomerization mechanisms play distinct roles: polymerization mediates the
      activation of the receptor by assembling monomers into 6- to 8-mer oligomers;
      condensation of the preassembled oligomers into large clusters containing
      hundreds of monomers dampens the signaling. We propose that the polymerization
      condensation dynamics creates mechanistic explanation for how cells properly
      respond to variable ligand concentrations and gradients.

PMID- 29192025
TI  - STOREKEEPER RELATED1/G-Element Binding Protein (STKR1) Interacts with Protein
      Kinase SnRK1.
AB  - Sucrose nonfermenting related kinase1 (SnRK1) is a conserved energy sensor kinase
      that regulates cellular adaptation to energy deficit in plants. Activation of
      SnRK1 leads to the down-regulation of ATP-consuming biosynthetic processes and
      the stimulation of energy-generating catabolic reactions by transcriptional
      reprogramming and posttranslational modifications. Although considerable progress
      has been made during the last years in understanding the SnRK1 signaling pathway,
      many of its components remain unidentified. Here, we show that the catalytic
      alpha-subunits KIN10 and KIN11 of the Arabidopsis (Arabidopsis thaliana) SnRK1
      complex interact with the STOREKEEPER RELATED1/G-Element Binding Protein (STKR1)
      inside the plant cell nucleus. Overexpression of STKR1 in transgenic Arabidopsis
      plants led to reduced growth, a delay in flowering, and strongly attenuated
      senescence. Metabolite profiling revealed that the transgenic lines exhausted
      their carbohydrates during the dark period to a greater extent than the wild type
      and accumulated a range of amino acids. At the global transcriptome level, genes
      affected by STKR1 overexpression were broadly associated with systemic acquired
      resistance, and transgenic plants showed enhanced resistance toward a virulent
      strain of the biotrophic oomycete pathogen Hyaloperonospora arabidopsidis Noco2.
      We discuss a possible connection of STKR1 function, SnRK1 signaling, and plant
      immunity.

PMID- 29192026
TI  - Reassessing the Roles of PIN Proteins and Anticlinal Microtubules during Pavement
      Cell Morphogenesis.
AB  - The leaf epidermis is a biomechanical shell that influences the size and shape of
      the organ. Its morphogenesis is a multiscale process in which nanometer-scale
      cytoskeletal protein complexes, individual cells, and groups of cells pattern
      growth and define macroscopic leaf traits. Interdigitated growth of neighboring
      cells is an evolutionarily conserved developmental strategy. Understanding how
      signaling pathways and cytoskeletal proteins pattern cell walls during this form
      of tissue morphogenesis is an important research challenge. The cellular and
      molecular control of a lobed cell morphology is currently thought to involve PIN
      FORMED (PIN)-type plasma membrane efflux carriers that generate subcellular auxin
      gradients. Auxin gradients were proposed to function across cell boundaries to
      encode stable offset patterns of cortical microtubules and actin filaments
      between adjacent cells. Many models suggest that long-lived microtubules along
      the anticlinal cell wall generate local cell wall heterogeneities that restrict
      local growth and specify the timing and location of lobe formation. Here, we used
      Arabidopsis (Arabidopsis thaliana) reverse genetics and multivariate long-term
      time-lapse imaging to test current cell shape control models. We found that
      neither PIN proteins nor long-lived microtubules along the anticlinal wall
      predict the patterns of lobe formation. In fields of lobing cells, anticlinal
      microtubules are not correlated with cell shape and are unstable at the time
      scales of cell expansion. Our analyses indicate that anticlinal microtubules have
      multiple functions in pavement cells and that lobe initiation is likely
      controlled by complex interactions among cell geometry, cell wall stress
      patterns, and transient microtubule networks that span the anticlinal and
      periclinal walls.

PMID- 29192027
TI  - Transcription Factor-Mediated Control of Anthocyanin Biosynthesis in Vegetative
      Tissues.
AB  - Plants accumulate secondary metabolites to adapt to environmental conditions.
      These compounds, here exemplified by the purple-colored anthocyanins, are
      accumulated upon high temperatures, UV-light, drought, and nutrient deficiencies,
      and may contribute to tolerance to these stresses. Producing compounds is often
      part of a more broad response of the plant to changes in the environment. Here we
      investigate how a transcription-factor-mediated program for controlling
      anthocyanin biosynthesis also has effects on formation of specialized cell
      structures and changes in the plant root architecture. A systems biology approach
      was developed in tomato (Solanum lycopersicum) for coordinated induction of
      biosynthesis of anthocyanins, in a tissue- and development-independent manner. A
      transcription factor couple from Antirrhinum that is known to control anthocyanin
      biosynthesis was introduced in tomato under control of a dexamethasone-inducible
      promoter. By application of dexamethasone, anthocyanin formation was induced
      within 24 h in vegetative tissues and in undifferentiated cells. Profiles of
      metabolites and gene expression were analyzed in several tomato tissues. Changes
      in concentration of anthocyanins and other phenolic compounds were observed in
      all tested tissues, accompanied by induction of the biosynthetic pathways leading
      from Glc to anthocyanins. A number of pathways that are not known to be involved
      in anthocyanin biosynthesis were observed to be regulated. Anthocyanin-producing
      plants displayed profound physiological and architectural changes, depending on
      the tissue, including root branching, root epithelial cell morphology, seed
      germination, and leaf conductance. The inducible anthocyanin-production system
      reveals a range of phenomena that accompanies anthocyanin biosynthesis in tomato,
      including adaptions of the plants architecture and physiology.

PMID- 29192028
TI  - The Impacts of Fluctuating Light on Crop Performance.
AB  - Rapidly changing light conditions can reduce carbon gain and productivity in
      field crops because photosynthetic responses to light fluctuations are not
      instantaneous. Plant responses to fluctuating light occur across levels of
      organizational complexity from entire canopies to the biochemistry of a single
      reaction and across orders of magnitude of time. Although light availability and
      variation at the top of the canopy are largely dependent on the solar angle and
      degree of cloudiness, lower crop canopies rely more heavily on light in the form
      of sunflecks, the quantity of which depends mostly on canopy structure but also
      may be affected by wind. The ability of leaf photosynthesis to respond rapidly to
      these variations in light intensity is restricted by the relatively slow
      opening/closing of stomata, activation/deactivation of C3 cycle enzymes, and up
      regulation/down-regulation of photoprotective processes. The metabolic complexity
      of C4 photosynthesis creates the apparently contradictory possibilities that C4
      photosynthesis may be both more and less resilient than C3 to dynamic light
      regimes, depending on the frequency at which these light fluctuations occur. We
      review the current understanding of the underlying mechanisms of these
      limitations to photosynthesis in fluctuating light that have shown promise in
      improving the response times of photosynthesis-related processes to changes in
      light intensity.

PMID- 29192031
TI  - Erratum.

PMID- 29192033
TI  - Feeling it.

PMID- 29192029
TI  - The Actin Cytoskeleton: Functional Arrays for Cytoplasmic Organization and Cell
      Shape Control.

PMID- 29192034
TI  - BVZS calls on the RCVS to reinstate its diploma in zoological medicine.

PMID- 29192036
TI  - Animal sentience: principle of Article 13 must be enshrined in UK law, say vets.

PMID- 29192030
TI  - The Plant Trans-Golgi Network: Not Just a Matter of Distinction.

PMID- 29192037
TI  - 'Remarkable year' for tackling antimicrobial resistance.

PMID- 29192041
TI  - Improving the welfare of working rams.

PMID- 29192042
TI  - Disease surveillance in England and Wales, November 2017.

PMID- 29192043
TI  - Acute hydrated non-compressive nucleus pulposus extrusion: what do we know so
      far?

PMID- 29192045
TI  - How resilient are vets and vet nurses?

PMID- 29192046
TI  - Who owns the countryside?

PMID- 29192047
TI  - Porcine circovirus type 3 in the UK.

PMID- 29192048
TI  - We must tie equine welfare to international development.

PMID- 29192049
TI  - George Rafferty.
AB  - A well-respected, understanding veterinary surgeon who was as comfortable with
      his clients as with the many species of animals he treated. He was Deputy Lord
      Lieutenant for Inverness-shire and was awarded an MBE for his services to
      agriculture.

PMID- 29192050
TI  - Nominations open for BVA Council regional representatives.
AB  - With a number of vacancies available on BVA Council, and the nomination period
      for BVA Junior Vice President 2018/19 coming up, Amelia Findon, BVA's Head of
      Policy and Governance, explains why there has never been a better time to get
      involved.

PMID- 29192053
TI  - BVA membership rates 2018.
AB  - BVA's Head of Membership, Tim Keen, outlines the BVA membership rates for 2018.

PMID- 29192052
TI  - Busy times for BVA at the London Vet Show.
AB  - Zoe Davies, BVA Marketing Manager, shares some of the highlights from this year's
      London Vet Show.

PMID- 29192054
TI  - Christmas advice to pass on to pet owners.
AB  - Pre-empting pet owners' Christmas pitfalls, BVA Media Officer Girija Duggal
      shares statistics from BVA's Voice of the Veterinary Profession survey and some
      top tips to help your clients avoid having to use the out-of-hours number.

PMID- 29192055
TI  - Young Vet Network Christmas veterinary care.
AB  - Becky Richardson, Young Vet Network representative on BVA Council, shares her
      tips for getting through a busy Christmas season as a new graduate vet.

PMID- 29192056
TI  - Transforming BVA headquarters.
AB  - BVA is embarking on an exciting project to transform its headquarters in London,
      writes Chief Executive David Calpin.

PMID- 29192057
TI  - Will you be lonely (working) this Christmas?
AB  - BVA is putting together some guidance on steps that vets and practices can take
      to mitigate the risks of lone working, as Laura Carleton, Member Services and
      Policy Support Officer, reports.

PMID- 29192060
TI  - High-content tripartite split-GFP cell-based assays to screen for modulators of
      small GTPase activation.
AB  - The human Ras superfamily of small GTPases controls essential cellular processes
      such as gene expression and cell proliferation. As their deregulation is widely
      associated with human cancer, small GTPases and their regulatory proteins have
      become increasingly attractive for the development of novel therapeutics.
      Classical methods to monitor GTPase activation include pulldown assays that limit
      the analysis of GTP-bound form of proteins from cell lysates. Alternatively, live
      cell FRET biosensors may be used to study GTPase activation dynamics in response
      to stimuli, but these sensors often require further optimization for high
      throughput applications. Here, we describe a cell-based approach that is suitable
      to monitor the modulation of small GTPase activity in a high-content analysis.
      The assay relies on a genetically encoded tripartite split-GFP (triSFP) system
      that we integrated in an optimized cellular model to monitor modulation of RhoA
      and RhoB GTPases. Our results indicate the robust response of the reporter,
      allowing the interrogation of inhibition and stimulation of Rho activity, and
      highlight potential applications of this method to discover novel modulators and
      regulators of small GTPases and related protein-binding domains.

PMID- 29192062
TI  - Distinct roles for plasma membrane PtdIns(4)P and PtdIns(4,5)P2 during receptor
      mediated endocytosis in yeast.
AB  - Clathrin-mediated endocytosis requires the coordinated assembly of various
      endocytic proteins and lipids at the plasma membrane. Accumulating evidence
      demonstrates a crucial role for phosphatidylinositol-4,5-bisphosphate
      [PtdIns(4,5)P2] in endocytosis but specific roles for phosphatidylinositol-4
      phosphate [PtdIns(4)P], other than as the biosynthetic precursor of
      PtdIns(4,5)P2, have not been clarified. In this study we investigated the roles
      of PtdIns(4)P and PtdIns(4,5)P2 in receptor-mediated endocytosis through the
      construction of temperature-sensitive (ts) mutants for the phosphatidylinositol 4
      kinases (PI4-kinases) Stt4p and Pik1p and the 1-phosphatidylinositol-4-phosphate
      5-kinase [PtdIns(4) 5-kinase] Mss4p. Quantitative analyses of endocytosis
      revealed that both the stt4tspik1ts and mss4ts mutants have a severe defect in
      endocytic internalization. Live-cell imaging of endocytic protein dynamics in
      stt4tspik1ts and mss4ts mutants revealed that PtdIns(4)P is required for the
      recruitment of the alpha-factor receptor Ste2p to clathrin-coated pits, whereas
      PtdIns(4,5)P2 is required for membrane internalization. We also found that the
      localization to endocytic sites of the ENTH/ANTH domain-bearing clathrin
      adaptors, Ent1p, Ent2p, Yap1801p and Yap1802p, is significantly impaired in the
      stt4tspik1ts mutant but not in the mss4ts mutant. These results suggest distinct
      roles in successive steps for PtdIns(4)P and PtdIns(4,5)P2 during receptor
      mediated endocytosis.

PMID- 29192061
TI  - NudE regulates dynein at kinetochores but is dispensable for other dynein
      functions in the C. elegans early embryo.
AB  - In mitosis, the molecular motor dynein is recruited to kinetochores by the Rod
      Zw10-Zwilch complex (RZZ) and Spindly to control spindle assembly checkpoint
      (SAC) signaling and microtubule attachment. How the ubiquitous dynein co-factors
      Lis1 and NudE contribute to these functions remains poorly understood. Here, we
      show that the C. elegans NudE homolog NUD-2 is dispensable for dynein- and LIS-1
      dependent mitotic spindle assembly in the zygote. This facilitates functional
      characterization of kinetochore-localized NUD-2, which is recruited by the CENP-F
      like proteins HCP-1 and HCP-2 independently of RZZ-Spindly and dynein-LIS-1.
      Kinetochore dynein levels are reduced in Deltanud-2 embryos, and, as occurs upon
      RZZ inhibition, loss of NUD-2 delays the formation of load-bearing kinetochore
      microtubule attachments and causes chromatin bridges in anaphase. Survival of
      Deltanud-2 embryos requires a functional SAC, and kinetochores without NUD-2
      recruit an excess of SAC proteins. Consistent with this, SAC signaling in early
      Deltanud-2 embryos extends mitotic duration and prevents high rates of chromosome
      mis-segregation. Our results reveal that both NUD-2 and RZZ-Spindly are essential
      for dynein function at kinetochores, and that the gain in SAC strength during
      early embryonic development is relevant under conditions that mildly perturb
      mitosis.

PMID- 29192063
TI  - Mechanism of inhibition of taurolithocholate-induced retrieval of plasma membrane
      MRP2 by cyclic AMP and tauroursodeoxycholate.
AB  - Taurolithocholate (TLC) produces cholestasis by inhibiting biliary solute
      secretion in part by retrieving MRP2 from the plasma membrane (PM).
      Tauroursodeoxycholate (TUDC) and cAMP reverse TLC-induced cholestasis by
      inhibiting TLC-induced retrieval of MRP2. However, cellular mechanisms for this
      reversal are incompletely understood. Recently, we reported that TLC decreases PM
      MRP2 by activating PKCepsilon followed by phosphorylation of myristoylated
      alanine-rich C kinase substrate (MARCKS). Thus, cAMP and TUDC may reverse TLC
      induced cholestasis by inhibiting the TLC/PKCepsilon/MARCKS phosphorylation
      pathway. We tested this hypothesis by determining whether TUDC and/or cAMP
      inhibit TLC-induced activation of PKCepsilon and phosphorylation of MARCKS
      Studies were conducted in HuH-NTCP cell line and rat hepatocytes. Activation of
      PKCepsilon was determined from the translocation of PKCepsilon to PM using a
      biotinylation method. Phosphorylation of MARCKS was determined by immunoblotting
      with a phospho-MARCKS antibody. TLC, but not cAMP and TUDC, activated PKCepsilon
      and increased MARCKS phosphorylation in HuH-NTCP as well in rat hepatocytes.
      Treatment with TUDC or cAMP inhibited TLC-induced activation of PKCepsilon and
      increases in MARCKS phosphorylation in both cell types. Based on these results,
      we conclude that the reversal of TLC-induced cholestasis by cAMP and TUDC
      involves, at least in part, inhibition of TLC-mediated activation of the
      PKCepsilon/MARCKS phosphorylation pathway.

PMID- 29192064
TI  - Fyn-binding protein ADAP supports actin organization in podocytes.
AB  - The renal podocyte is central to the filtration function of the kidney that is
      dependent on maintaining both highly organized, branched cell structures forming
      foot processes, and a unique cell-cell junction, the slit diaphragm. Our recent
      studies investigating the developmental formation of the slit diaphragm
      identified a novel claudin family tetraspannin, TM4SF10, which is a binding
      partner for ADAP (also known as Fyn binding protein Fyb). To investigate the role
      of ADAP in podocyte function in relation to Fyn and TM4SF10, we examined ADAP
      knockout (KO) mice and podocytes. ADAP KO mice developed glomerular pathology
      that began as hyalinosis and progressed to glomerulosclerosis, with aged male
      animals developing low levels of albuminuria. Podocyte cell lines established
      from the KO mice had slower attachment kinetics compared to wild-type cells,
      although this did not affect the total number of attached cells nor the ability
      to form focal contacts. After attachment, the ADAP KO cells did not attain
      typical podocyte morphology, lacking the elaborate cell protrusions typical of
      wild-type podocytes, with the actin cytoskeleton forming circumferential stress
      fibers. The absence of ADAP did not alter Fyn levels nor were there differences
      between KO and wild-type podocytes in the reduction of Fyn activating
      phosphorylation events with puromycin aminonucleoside treatment. In the setting
      of endogenous TM4SF10 overexpression, the absence of ADAP altered the formation
      of cell-cell contacts containing TM4SF10. These studies suggest ADAP does not
      alter Fyn activity in podocytes, but appears to mediate downstream effects of Fyn
      controlled by TM4SF10 involving actin cytoskeleton organization.

PMID- 29192065
TI  - Peripheral nerve function estimation by linear model of multi-CMAP responses for
      surgical intervention in acoustic neuroma surgery.
AB  - Nerve function assessments are crucial for surgical intervention during acoustic
      neuroma surgery. Cranial nerves such as acoustic and facial nerves, can be
      possibly damaged during tumor dissection. Proper surgical intervention should
      prevent neurological deficit and achieve total tumor removal. Conventionally,
      nerve function is qualitatively evaluated by surgeon and neurologist. Facial
      nerves can be preserved by monitoring the compound muscle action potential (CMAP)
      response. The differences in the amplitude and latency of CMAP are used as
      indicators during surgical interventions. However, baseline CMAPs cannot be
      recorded in the presence of large acoustic tumors. This paper presents a new way
      of estimating nerve function. Instead of a single CMAP examination, multi-CMAP
      responses are obtained from a train of varied stimulus intensities and these are
      applied a mathematical model. Shifts in the mathematical model parameters reflect
      changes in facial nerve function. In this study, experiments conducted in frog
      revealed that shifts in the linear model parameters were related to the level of
      induced nerve injury. Significant differences in the slope parameter of the
      linear model were found between each nerve condition. The identification of
      healthy and severed nerves via a support vector machine (SVM) corresponded to 94%
      accuracy. This classification criterion could be used with surgical intervention
      to prevent severed facial nerve palsy in acoustic neuroma surgery. The proposed
      method could be used to estimate nerve outcomes without prior information of a
      CMAP baseline.

PMID- 29192066
TI  - Epinephrine stimulates CXCL1 IL-1alpha, IL-6 secretion in isolated mouse limb
      muscle.
AB  - Catecholamines stimulate interleukin-6 (IL-6) secretion in skeletal muscles.
      However, whether other cytokines are secreted is currently unknown. Skeletal
      muscle ex vivo preparations commonly used to study cytokine secretion have dealt
      with limitations including auto-oxidation of catecholamines. The use of metal
      chelators could be an alternative to avoid auto-oxidation and allow
      catecholamines to be used at physiological doses. We exposed isolated soleus
      muscles to 1 or 100 ng/mL epinephrine (EPI) and collected bath samples at 1 and 2
      h for multiplex cytokine analysis. Keratinocyte chemoattractant (CXCL1), IL-6,
      and IL-1alpha were significantly elevated by 100 ng/mL exposure, but not by 1
      ng/mL (median [CXCL1] (2 h) = 83 pg/mL; [IL-6] = 19 pg/mL; IL-1alpha = 7.5
      pg/mL). CXCL1 and IL-6 were highly correlated in each sample (P = 0.0001). A
      second experiment combined the metal chelator, deferoxamine mesylate (DFO), to
      prevent EPI autoxidation, with 2 ng/mL EPI and 10.5 ng/mL norepinephrine (NOREPI)
      to mimic peak exercise. Unexpectedly, DFO alone stimulated both IL-6 and CXCL1
      secretion, but together with EPI and NOREPI had no additional effects.
      Stimulation of cytokine secretory responses from skeletal muscle cells in
      response to DFO thus precludes its use as a chelating agent in ex vivo models. In
      conclusion, 100 ng/mL EPI stimulates a robust secretory CXCL1 response, which
      together with IL-6 and IL-1alpha, may constitute an adrenal-muscle endocrine
      response system.

PMID- 29192068
TI  - Passive elongation of muscle fascicles in human muscles with short and long
      tendons.
AB  - This study tested the hypothesis that the ratio of changes in muscle fascicle and
      tendon length that occurs with joint movement scales linearly with the ratio of
      the slack lengths of the muscle fascicles and tendons. We compared the
      contribution of muscle fascicles to passive muscle-tendon lengthening in muscles
      with relatively short and long fascicles. Fifteen healthy adults participated in
      the study. The medial gastrocnemius, tibialis anterior, and brachialis muscle
      tendon units were passively lengthened by slowly rotating the ankle or elbow.
      Change in muscle fascicle length was measured with ultrasonography. Change in
      muscle-tendon length was calculated from estimated muscle moment arms. Change in
      tendon length was calculated by subtracting change in fascicle length from change
      in muscle-tendon length. The median (IQR) contribution of muscle fascicles to
      passive lengthening of the muscle-tendon unit, measured as the ratio of the
      change in fascicle length to the change in muscle-tendon unit length, was 0.39
      (0.26-0.48) for the medial gastrocnemius, 0.51 (0.29-0.60) for tibialis anterior,
      and 0.65 (0.49-0.90) for brachialis. Brachialis muscle fascicles contributed to
      muscle-tendon unit lengthening significantly more than medial gastrocnemius
      muscle fascicles, but less than would be expected if the fascicle contribution
      scaled linearly with the ratio of muscle fascicle and tendon slack lengths.

PMID- 29192067
TI  - Effect of myostatin deletion on cardiac and microvascular function.
AB  - The objective of this study is to test the hypothesis that increased muscle mass
      has positive effects on cardiovascular function. Specifically, we tested the
      hypothesis that increases in lean body mass caused by deletion of myostatin
      improves cardiac performance and vascular function. Echocardiography was used to
      quantify left ventricular function at baseline and after acute administration of
      propranolol and isoproterenol to assess beta-adrenergic reactivity. Additionally,
      resistance vessels in several beds were removed, cannulated, pressurized to 60
      mmHg and reactivity to vasoactive stimuli was assessed. Hemodynamics were
      measured using in vivo radiotelemetry. Myostatin deletion results in increased
      fractional shortening at baseline. Additionally, arterioles in the coronary and
      muscular microcirculations are more sensitive to endothelial-dependent dilation
      while nonmuscular beds or the aorta were unaffected. beta-adrenergic dilation was
      increased in both coronary and conduit arteries, suggesting a systemic effect of
      increased muscle mass on vascular function. Overall hemodynamics and physical
      characteristics (heart weight and size) remained unchanged. Myostatin deletion
      mimics in part the effects of exercise on cardiovascular function. It
      significantly increases lean muscle mass and results in muscle-specific increases
      in endothelium-dependent vasodilation. This suggests that increases in muscle
      mass may serve as a buffer against pathological states that specifically target
      cardiac function (heart failure), the beta-adrenergic system (age), and nitric
      oxide bio-availability (atherosclerosis). Taken together, pharmacological
      inhibition of the myostatin pathway could prove an excellent mechanism by which
      the benefits of exercise can be conferred in patients that are unable to
      exercise.

PMID- 29192069
TI  - Full-Length Genome Sequence of Japanese Encephalitis Virus Strain FC792, Isolated
      from Guangxi, China.
AB  - We report here the complete genomic sequence of Japanese encephalitis virus (JEV)
      strain FC792, isolated from aborted fetuses of sows which were unimmunized with
      JEV vaccines in Guangxi Province, southern China. The complete JEV genome of
      strain FC792 had the highest nucleotide homology (99.7%) and amino acid identity
      (99.4%) with the sequence of JEV strain SA14-14-2 (GenBank accession number
      AF315119). Phylogenetic analysis showed that strain FC792 had the closest
      phylogenetic relationship to the sequence of strain YUNNAN0901 (GenBank accession
      number JQ086762). This study will help us understand the molecular pathogenesis
      and genetic diversity of genotype III Japanese encephalitis virus in pigs.

PMID- 29192070
TI  - Novel Reassortant H3N2 Avian Influenza Virus Isolated from Domestic Ducks in
      Eastern China in 2016.
AB  - H3 subtype avian influenza virus (AIV) poses a great threat to public health, and
      so investigating its epidemiology is of great importance. A novel reassortant
      H3N2 AIV strain was isolated from a live poultry market in eastern China. The
      strain's genes originated from H1N1, H3, and H7 AIVs. Thus, the genome
      information of the H3N2 isolate will help to investigate further the epidemiology
      of H3 subtype AIVs in China.

PMID- 29192071
TI  - Complete Genome Sequence of a Divergent Human Rhinovirus C Isolate from an Infant
      with Severe Community-Acquired Pneumonia in Colorado, USA.
AB  - Here, we report the genome sequence of a divergent human rhinovirus C isolate
      identified from an infant with a severe community-acquired respiratory infection.
      RNA sequencing performed on an Illumina platform identified reads aligning to
      human rhinovirus species, which were de novo assembled to produce a coding
      complete genome sequence.

PMID- 29192072
TI  - Complete Genome Sequence of Bacillus velezensis L-1, Which Has Antagonistic
      Activity against Pear Diseases.
AB  - Bacillus velezensis L-1 is an effective biocontrol agent against pear diseases.
      Here, we report the complete genome sequence of B. velezensis L-1 in which
      clusters related to the biosynthesis of secondary metabolites were predicted.
      This genome provides insights into the possible biocontrol mechanisms and
      furthers application of this specific bacterium.

PMID- 29192073
TI  - Complete Genome Sequence of a New Isolate of Solenopsis invicta virus 3 from
      Solenopsis invicta * richteri Hybrid Ants.
AB  - Solenopsis invicta virus 3 (SINV-3) is a positive-sense, single-stranded RNA
      virus that infects the red imported fire ant, Solenopsis invicta Buren. We report
      here the full genome (10,383 nucleotides) of an isolate infecting Solenopsis
      invicta * richteri hybrid ants, which we have identified as SINV-3 hybrid.

PMID- 29192074
TI  - Draft Genome Sequence of Leuconostoc citreum CW28 Isolated from Pozol, a Pre
      Hispanic Fermented Corn Beverage.
AB  - Leuconostoc citreum CW28 was isolated from pozol, a Mayan fermented corn
      beverage. This strain produces a cell-associated inulosucrase, the first
      described in bacteria. Its draft genome sequence, announced here, has an
      estimated size of 1.98 Mb and harbors 1,915 coding genes, 12 rRNAs, 68 tRNAs, 17
      putative pseudogenes, and 1 putative phage.

PMID- 29192075
TI  - Complete Genome Sequence of a Papaya ringspot virus Isolate from South Korea That
      Infects Cucurbita pepo.
AB  - The complete genome sequence of a Papaya ringspot virus (PRSV) isolate from South
      Korea (SK) infecting squash (Cucurbita pepo) was obtained using paired-end RNA
      sequencing. A BLASTn search of the PRSV SK isolate full-genome sequence showed
      nucleotide sequence identity ranging from 81% to 83% with previously reported
      PRSV isolates (GenBank accession numbers KX655874 and EF017707).

PMID- 29192076
TI  - Closed Genome Sequence of Chryseobacterium piperi Strain CTMT/ATCC BAA-1782, a
      Gram-Negative Bacterium with Clostridial Neurotoxin-Like Coding Sequences.
AB  - Clostridial neurotoxins, including botulinum and tetanus neurotoxins, are among
      the deadliest known bacterial toxins. Until recently, the horizontal mobility of
      this toxin gene family appeared to be limited to the genus Clostridium We report
      here the closed genome sequence of Chryseobacterium piperi, a Gram-negative
      bacterium containing coding sequences with homology to clostridial neurotoxin
      family proteins.

PMID- 29192077
TI  - Complete Genome Sequence of Bacillus vallismortis NBIF-001, a Novel Strain from
      Shangri-La, China, That Has High Activity against Fusarium oxysporum.
AB  - Bacillus vallismortis NBIF-001, a Gram-positive bacterium, was isolated from soil
      in Shangri-La, China. Here, we provide the complete genome sequence of this
      bacterium, which has a 3,929,787-bp-long genome, including 4,030 protein-coding
      genes and 195 RNA genes. This strain possesses a number of genes encoding
      virulence factors of pathogens.

PMID- 29192078
TI  - Genome Sequence of Bacillus velezensis S141, a New Strain of Plant Growth
      Promoting Rhizobacterium Isolated from Soybean Rhizosphere.
AB  - Bacillus velezensis strain S141 is a plant growth-promoting rhizobacterium
      isolated from soybean (Glycine max) rhizosphere that enhances soybean growth,
      nodulation, and N2 fixation efficiency by coinoculation with Bradyrhizobium
      diazoefficiens USDA110. The S141 genome was identified to comprise a 3,974,582-bp
      long circular DNA sequence encoding at least 3,817 proteins.

PMID- 29192079
TI  - Complete Genome Sequence of Acetobacter pomorum Oregon-R-modENCODE Strain BDGP5,
      an Acetic Acid Bacterium Found in the Drosophila melanogaster Gut.
AB  - Acetobacter pomorum Oregon-R-modENCODE strain BDGP5 was isolated from Drosophila
      melanogaster for functional host-microbe interaction studies. The complete genome
      is composed of a single chromosomal circle of 2,848,089 bp, with a G+C content of
      53% and three plasmids of 131,455 bp, 19,216 bp, and 9,160 bp.

PMID- 29192080
TI  - Draft Genome Sequence of Heavy Metal-Resistant Soil Bacterium Serratia marcescens
      S2I7, Which Has the Ability To Degrade Polyaromatic Hydrocarbons.
AB  - Serratia marcescens S2I7 is a heavy metal-resistant, polyaromatic hydrocarbon
      degrading bacterium isolated from petroleum-contaminated sites. The genome
      contains one circular chromosome (5,241,555 bp; GC content 60.1%) with 4,533
      coding sequences. The draft genome sequence includes specific genetic elements
      for degradation of hydrocarbons and for heavy metal resistance.

PMID- 29192081
TI  - Draft Genome Sequence of Alcaligenes faecalis BDB4, a Polyaromatic Hydrocarbon
      Degrading Bacterium Isolated from Crude Oil-Contaminated Soil.
AB  - Alcaligenes fecalis BDB4 was isolated from crude oil-contaminated soil in India.
      The genome sequence of A. faecalis BDB4 revealed the presence of important genes
      required for polyaromatic hydrocarbon (PAH) metabolism and other associated
      functions, such as chemotaxis, membrane transport, and biofilm formation, giving
      insight into the complete PAH mineralization potential of this bacterium.

PMID- 29192082
TI  - Complete Genome Sequence of Bacillus velezensis YJ11-1-4, a Strain with Broad
      Spectrum Antimicrobial Activity, Isolated from Traditional Korean Fermented
      Soybean Paste.
AB  - Bacillus velezensis YJ11-1-4 is a strain that exhibits broad-spectrum
      antimicrobial activity against various pathogens. It was isolated from doenjang,
      a traditional Korean fermented soybean paste. The genome comprises a single
      circular chromosome of 4,006,637 bp with 46.42% G+C content without plasmids.

PMID- 29192083
TI  - Complete Chromosome Sequence of a Mycolactone-Producing Mycobacterium,
      Mycobacterium pseudoshottsii.
AB  - Mycobacterium pseudoshottsii is a fish pathogen that produces mycolactone. Here,
      we report the complete chromosome sequence of a type strain of M. pseudoshottsii
      (JCM 15466). The sequence will represent essential data for future phylogenetic
      and comparative genome studies of mycolactone-producing mycobacteria.

PMID- 29192084
TI  - Two Draft Genome Sequences of Sphingobacterium sp. Strains Isolated from Honey.
AB  - Here, we report two annotated draft genome sequences of Sphingobacterium sp.
      strains isolated from honey. The genomes of strains 1.A.4 and 1.A.5 show a
      limited similarity to each other and to genomes of other Sphingobacterium
      species, indicating that these isolates may represent new species.

PMID- 29192085
TI  - Draft Genome Sequence of Vibrio splendidus DSM 19640.
AB  - Here, we present the draft genome sequence of Vibrio splendidus type strain DSM
      19640. V. splendidus is an abundant species among coastal vibrioplankton. The
      assembly resulted in a 5,729,362-bp draft genome with 5,032 protein-coding
      sequences, 6 rRNAs, and 117 tRNAs.

PMID- 29192086
TI  - High-Quality Draft Genome Sequence of Curtobacterium sp. Strain Ferrero.
AB  - Here, we present the high-quality draft genome sequence of Curtobacterium sp.
      strain Ferrero, an actinobacterium belonging to a novel species isolated as an
      environmental contaminant in a bacterial cell culture. The assembled genome of
      3,694,888 bp in 49 contigs has a G+C content of 71.6% and contains 3,516
      predicted genes.

PMID- 29192087
TI  - Draft Genome Sequence of a Clinical Enterococcus faecium Sequence Type 18 Strain
      from South Africa.
AB  - We report the first draft genome sequence of an Enterococcus faecium sequence
      type 18 (ST18) strain isolated from a tuberculosis patient in Africa. The genome
      is comprised of 3,202,539 bp, 501 contigs, 37.70% GC content, 3,202 protein
      encoding genes, and 61 RNA genes. The resistome and virulome of this important
      pathogen are presented herein.

PMID- 29192088
TI  - Complete Genome Sequence of Bacillus altitudinis P-10, a Potential Bioprotectant
      against Xanthomonas oryzae pv. oryzae, Isolated from Rice Rhizosphere in Java,
      Indonesia.
AB  - Bacillus altitudinis P-10 was isolated from the rhizosphere of rice grown in an
      organic rice field and provides strong antagonism against the bacterial blight
      caused by Xanthomonas oryzae pv. oryzae in rice. Herein, we provide the complete
      genome sequence and a possible explanation of the antibiotic function of the P-10
      strain.

PMID- 29192089
TI  - Draft Genome Sequence of Pseudomonas aeruginosa ATCC 9027, Originally Isolated
      from an Outer Ear Infection.
AB  - Pseudomonas aeruginosa ATCC 9027 was isolated in 1943 from a case of otitis
      externa and is commonly employed as a quality control strain for sterility,
      assessment of antibiofilm agents, and in vitro study of wound infection. Here, we
      present the 6.34-Mb draft genome sequence and highlight some pertinent genes that
      are associated with virulence.

PMID- 29192090
TI  - Complete Genome Sequence of Lactobacillus plantarum 10CH, a Potential Probiotic
      Lactic Acid Bacterium with Potent Antimicrobial Activity.
AB  - Lactobacillus plantarum 10CH is a bacteriocin-producing potential probiotic
      lactic acid bacterium (LAB) strain isolated from cheese. Its complete nucleotide
      sequence shows a single circular chromosome of 3.3 Mb, with a G+C content of
      44.51%, a 25-gene plantaricin bacteriocin gene cluster, and the absence of
      recognized virulence factors.

PMID- 29192091
TI  - Whole-Mount Immunocytochemistry in Xenopus.
AB  - To visualize the effects of experimental perturbations on normal cellular
      behavior, morphology, and intracellular organization, we use a simple whole-mount
      immunocytochemical method with Xenopus oocytes, explants, or embryos. This method
      is applicable to a wide range of systems, including human-induced pluripotent
      stem cell-derived organoids, and can be used with both chromogenic (horseradish
      peroxidase/diaminobenzidine) and fluorescent imaging.

PMID- 29192092
TI  - Long term hormonal treatment for transgender people.

PMID- 29192093
TI  - 8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect
      (ITCO#2).

PMID- 29192095
TI  - Health effects of exposure to second- and third-hand marijuana smoke: a
      systematic review.
AB  - BACKGROUND: Recreational marijuana has been legalized in 11 jurisdictions; Canada
      will legalize marijuana by July 2018. With this changing landscape, there is a
      need to understand the public health risks associated with marijuana to support
      patient-care provider conversations, harm-reduction measures and evidence
      informed policy. The objective of this work was to summarize the health effects
      of exposure to second- and third-hand marijuana smoke. METHODS: In this
      systematic review, we searched 6 databases from inception to October 2017.
      Abstract and full-text review was conducted in duplicate. Studies were included
      if they were human, in vivo or in vitro studies with more than 1 case reported in
      English or French, and reported original, quantitative data. Three outcomes were
      extracted: 1) cannabinoids and cannabinoid metabolites in bodily fluids, 2) self
      reported psychoactive effects and 3) eye irritation and discomfort. RESULTS: Of
      the 1701 abstracts identified, 60 proceeded to full-text review; the final data
      set contained 15 articles. All of the included studies were of good to poor
      quality as assessed with the Downs and Black checklist. There is evidence of a
      direct relation between the tetrahydrocannabinol content of marijuana and effects
      on those passively exposed. This relation is mediated by several environmental
      factors including the amount of smoke, ventilation, air volume, number of
      marijuana cigarettes lit and number of smokers present. No evidence was
      identified assessing exposure to third-hand marijuana smoke or the health effects
      of long-term exposure. INTERPRETATION: Exposure to second-hand marijuana smoke
      leads to cannabinoid metabolites in bodily fluids, and people experience
      psychoactive effects after such exposure. Alignment of tobacco and marijuana
      smoking bylaws may result in the most effective public policies. More research is
      required to understand the impact of exposure to third-hand smoke and the health
      effects of long-term exposure to second-hand smoke.

PMID- 29192094
TI  - Overproduction of growth differentiation factor 15 promotes human rhinovirus
      infection and virus-induced inflammation in the lung.
AB  - Human rhinovirus (HRV) is the most common virus contributing to acute
      exacerbations of chronic obstructive pulmonary disease (COPD) nearly year round,
      but the mechanisms have not been well elucidated. Recent clinical studies suggest
      that high levels of growth differentiation factor 15 (GDF15) protein in the blood
      are associated with an increased yearly rate of all-cause COPD exacerbations.
      Therefore, in the current study, we investigated whether GDF15 promotes HRV
      infection and virus-induced lung inflammation. We first examined the role of
      GDF15 in regulating host defense and HRV-induced inflammation using human GDF15
      transgenic mice and cultured human GDF15 transgenic mouse tracheal epithelial
      cells. Next, we determined the effect of GDF15 on viral replication, antiviral
      responses, and inflammation in human airway epithelial cells with GDF15 knockdown
      and HRV infection. Finally, we explored the signaling pathways involved in airway
      epithelial responses to HRV infection in the context of GDF15. Human GDF15
      protein overexpression in mice led to exaggerated inflammatory responses to HRV,
      increased infectious particle release, and decreased IFN-lambda2/3 (IL-28A/B)
      mRNA expression in the lung. Moreover, GDF15 facilitated HRV replication and
      inflammation via inhibiting IFN-lambda1/IL-29 protein production in human airway
      epithelial cells. Lastly, Smad1 cooperated with interferon regulatory factor 7
      (IRF7) to regulate airway epithelial responses to HRV infection partly via GDF15
      signaling. Our results reveal a novel function of GDF15 in promoting lung HRV
      infection and virus-induced inflammation, which may be a new mechanism for the
      increased susceptibility and severity of respiratory viral (i.e., HRV) infection
      in cigarette smoke-exposed airways with GDF15 overproduction.

PMID- 29192096
TI  - Think Twice.

PMID- 29192097
TI  - Genomics in general practice: Generation Genome.

PMID- 29192098
TI  - Self-harm in young people: a challenge for general practice.

PMID- 29192099
TI  - Metal-on-metal hip replacements: implications for general practice.

PMID- 29192100
TI  - Inequality, austerity, Brexit, and health care.

PMID- 29192101
TI  - Interface medicine.

PMID- 29192102
TI  - Pharmacists are not physician assistants.

PMID- 29192103
TI  - Patient use of blood pressure self-screening facilities in general practice
      waiting rooms.

PMID- 29192104
TI  - Viewpoint: Do any of us truly have the capacity to consent?

PMID- 29192105
TI  - General practice should hold government to account on disease prevention.

PMID- 29192106
TI  - DART: a new look at the 2-week wait suspected cancer referral process.

PMID- 29192107
TI  - Practising humility: how philosophy can inform general practice.

PMID- 29192108
TI  - Bad Medicine: Polypharmacy.

PMID- 29192109
TI  - Yonder: Truthfulness, group visits, new care models, and a sense of calling.

PMID- 29192110
TI  - US executions: fight, fudge, or fold?

PMID- 29192111
TI  - Exhibition - La Dolce Vita: cultural adventures with a 5-year-old.

PMID- 29192115
TI  - Meniere's: why its diagnosis calls for more careful evaluation.

PMID- 29192116
TI  - GPs - at home with science and the humanities?

PMID- 29192117
TI  - Should GPs provide spiritual care?

PMID- 29192118
TI  - Point-of-care Helicobacter pylori testing: primary care technology update.

PMID- 29192119
TI  - Misdiagnosis of a hidden cause of hypertension: a case report.

PMID- 29192120
TI  - Making a positive diagnosis of irritable bowel syndrome.

PMID- 29192121
TI  - Don't judge a cell by its cover: heterogeneity within early lymphoid progenitors.

PMID- 29192122
TI  - Propofol Is an Allosteric Agonist with Multiple Binding Sites on Concatemeric
      Ternary GABAA Receptors.
AB  - GABAA receptors can be directly activated and potentiated by the intravenous
      anesthetic propofol. Previous photolabeling, modeling, and functional data have
      identified two binding domains through which propofol acts on the GABAA receptor.
      These domains are defined by the beta(M286) residue at the beta"+"-alpha"-"
      interface in the transmembrane region and the beta(Y143) residue near the beta"-"
      surface in the junction between the extracellular and transmembrane domains. In
      the ternary receptor, there are predicted to be two copies of each class of
      sites, for a total of four sites per receptor. We used beta2alpha1gamma2L and
      beta2alpha1 concatemeric constructs to determine the functional effects of the
      beta(Y143W) and beta(M286W) mutations to gain insight into the number of
      functional binding sites for propofol and the energetic contributions stemming
      from propofol binding to the individual sites. A mutation of each of the four
      sites affected the response to propofol, indicating that each of the four sites
      is functional in the wild-type receptor. The mutations mainly impaired
      stabilization of the open state by propofol, i.e., reduced gating efficacy. The
      effects were similar for mutations at either site and were largely additive and
      independent of the presence of other Y143W or M286W mutations in the receptor.
      The two classes of sites appeared to differ in affinity for propofol, with the
      site affected by M286W having about a 2-fold higher affinity. Our analysis
      indicates there may be one or two additional functionally equivalent binding
      sites for propofol, other than those modified by substitutions at beta(Y143) and
      beta(M286).

PMID- 29192123
TI  - Slowly Signaling G Protein-Biased CB2 Cannabinoid Receptor Agonist LY2828360
      Suppresses Neuropathic Pain with Sustained Efficacy and Attenuates Morphine
      Tolerance and Dependence.
AB  - The CB2 cannabinoid agonist LY2828360 lacked both toxicity and efficacy in a
      clinical trial for osteoarthritis. Whether LY2828360 suppresses neuropathic pain
      has not been reported, and its signaling profile is unknown. In vitro, LY2828360
      was a slowly acting but efficacious G protein-biased CB2 agonist, inhibiting cAMP
      accumulation and activating extracellular signal-regulated kinase 1/2 signaling
      while failing to recruit arrestin, activate inositol phosphate signaling, or
      internalize CB2 receptors. In wild-type (WT) mice, LY2828360 (3 mg/kg per day
      i.p. * 12 days) suppressed chemotherapy-induced neuropathic pain produced by
      paclitaxel without producing tolerance. Antiallodynic efficacy of LY2828360 was
      absent in CB2 knockout (KO) mice. Morphine (10 mg/kg per day i.p. * 12 days)
      tolerance developed in CB2KO mice but not in WT mice with a history of LY2828360
      treatment (3 mg/kg per day i.p. * 12 days). LY2828360-induced antiallodynic
      efficacy was preserved in WT mice previously rendered tolerant to morphine (10
      mg/kg per day i.p. * 12 days), but it was absent in morphine-tolerant CB2KO mice.
      Coadministration of LY2828360 (0.1 mg/kg per day i.p. * 12 days) with morphine
      (10 mg/kg per day * 12 days) blocked morphine tolerance in WT but not in CB2KO
      mice. WT mice that received LY2828360 coadministered with morphine exhibited a
      trend (P = 0.055) toward fewer naloxone-precipitated jumps compared with CB2KO
      mice. In conclusion, LY2828360 is a slowly signaling, G protein-biased CB2
      agonist that attenuates chemotherapy-induced neuropathic pain without producing
      tolerance and may prolong effective opioid analgesia while reducing opioid
      dependence. LY2828360 may be useful as a first-line treatment in chemotherapy
      induced neuropathic pain and may be highly efficacious in neuropathic pain states
      that are refractive to opioid analgesics.

PMID- 29192124
TI  - Drugs and Scaffold That Inhibit Cytochrome P450 27A1 In Vitro and In Vivo.
AB  - Cytochrome P450 27A1 (CYP27A1) is a ubiquitous enzyme that hydroxylates
      cholesterol and other sterols. Complete CYP27A1 deficiency owing to genetic
      mutations is detrimental to human health, whereas 50% of activity retention is
      not and does not affect the whole body cholesterol levels. CYP27A1 is considered
      a potential therapeutic target in breast cancer and age-related neurodegenerative
      diseases; however, CYP27A1 inhibition should be <=50%. Herein, 131
      pharmaceuticals were tested for their effect on CYP27A1-mediated cholesterol 27
      hydroxylation by in vitro enzyme assay. Of them, 14 drugs inhibited CYP27A1 by
      >=75% and were evaluated for in vitro binding to the enzyme active site and for
      inhibition constants. All drugs except one (dasatinib) elicited a spectral
      response in CYP27A1 and had Ki values for cholesterol 27-hydroxylation either in
      the submicromolar (clevidipine, delavirdine, etravirine, felodipine, nicardipine,
      nilotinib, and sorafenib) or low micromolar range (abiratone, candesartan,
      celecoxib, dasatinib, nilvadipine, nimodipine, and regorafenib). Clevidipine,
      felodipine, nicardipine, nilvadipine, and nimodipine have the same 1,4
      dihydropyridine scaffold and are indicated for hypertension. We used two of these
      antihypertensives (felodipine and nilvadipine) for administration to mice at a 1
      mg/kg of body weight dose, daily, for 7 days. Mouse 27-hydroxycholesterol levels
      in the plasma, brain, and liver were reduced, whereas tissue levels of total
      cholesterol were unchanged. Structure-activity relationships within the 1,4
      dihydropyridine scaffold were investigated, and features important for CY27A1
      inhibition were identified. We confirmed our previous finding that CYP27A1 is a
      druggable enzyme and found additional drugs as well as the scaffold with
      potential for partial CYP27A1 inhibition in humans.

PMID- 29192125
TI  - Endocannabinoid-Specific Impairment in Synaptic Plasticity in Striatum of
      Huntington's Disease Mouse Model.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disease affecting
      predominantly striatum and cortex that results in motor and cognitive disorders.
      Before a motor phenotype, animal models of HD show aberrant cortical-striatal
      glutamate signaling. Here, we tested synaptic plasticity of cortical excitatory
      synapses onto striatal spiny projection neurons (SPNs) early in the YAC128 mouse
      model of HD. High-frequency stimulation-induced long-term depression, mediated by
      the endocannabinoid anandamide and cannabinoid receptor 1 (CB1), was
      significantly attenuated in male and female YAC128 SPNs. Indirect pathway SPNs,
      which are more vulnerable in HD, were most affected. Our experiments show
      metabotropic glutamate receptor and endocannabinoid 2-arachidonoylglycerol
      dependent plasticity, as well as direct CB1 activation by agonists, was similar
      in YAC128 and FVB/N wild-type SPNs suggesting that presynaptic CB1 is functioning
      normally. These results are consistent with a specific impairment in postsynaptic
      anandamide synthesis in YAC128 SPN. Strikingly, although suppression of
      degradation of anandamide was not effective, elevating 2-arachidonoylglycerol
      levels restored long-term depression in YAC128 striatal neurons. Together, these
      results have potential implications for neuroprotection and ameliorating early
      cognitive and motor deficits in HD.SIGNIFICANCE STATEMENT Huntington's disease
      (HD) is an inherited neurodegenerative disease with no cure. Recent studies find
      impairment of the endocannabinoid system in animal models but the functional
      implication for synaptic plasticity in HD remains unclear. Sepers et al. show a
      selective deficit in synaptic plasticity mediated by the endocannabinoid
      anandamide, but not 2-arachidonoylglycerol in a mouse model of HD. The deficit is
      rescued by selectively elevating levels of 2-arachidonoylglycerol produced on
      demand. This mechanism could be targeted in the development of future
      therapeutics for HD.

PMID- 29192126
TI  - Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in
      Aging.
AB  - The medial temporal lobe (MTL) is an early site of tau accumulation and MTL
      dysfunction may underlie episodic-memory decline in aging and dementia.
      Postmortem data indicate that tau pathology in the transentorhinal cortex is
      common by age 60, whereas spread to neocortical regions and worsening of
      cognition is associated with beta-amyloid (Abeta). We used [18F]AV-1451 and
      [11C]PiB positron emission tomography, structural MRI, and neuropsychological
      assessment to investigate how in vivo tau accumulation in temporal lobe regions,
      Abeta, and MTL atrophy contribute to episodic memory in cognitively normal older
      adults (n = 83; age, 77 +/- 6 years; 58% female). Stepwise regressions identified
      tau in MTL regions known to be affected in old age as the best predictor of
      episodic-memory performance independent of Abeta status. There was no interactive
      effect of MTL tau with Abeta on memory. Higher MTL tau was related to higher age
      in the subjects without evidence of Abeta. Among temporal lobe subregions,
      episodic memory was most strongly related to tau-tracer uptake in the
      parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our
      parcellation includes the transentorhinal cortex. In subjects with longitudinal
      MRI and cognitive data (n = 57), entorhinal atrophy mirrored patterns of tau
      pathology and their relationship with memory decline. Our data are consistent
      with neuropathological studies and further suggest that entorhinal tau pathology
      underlies memory decline in old age even without Abeta.SIGNIFICANCE STATEMENT Tau
      tangles and beta-amyloid (Abeta) plaques are key lesions in Alzheimer's disease
      (AD) but both pathologies also occur in cognitively normal older people.
      Neuropathological data indicate that tau tangles in the medial temporal lobe
      (MTL) underlie episodic-memory impairments in AD dementia. However, it remains
      unclear whether MTL tau pathology also accounts for memory impairments often seen
      in elderly people and how Abeta affects this relationship. Using tau-specific and
      Abeta-specific positron emission tomography tracers, we show that in vivo MTL tau
      pathology is associated with episodic-memory performance and MTL atrophy in
      cognitively normal adults, independent of Abeta. Our data point to MTL tau
      pathology, particularly in the entorhinal cortex, as a substrate of age-related
      episodic-memory loss.

PMID- 29192127
TI  - Compressive Temporal Summation in Human Visual Cortex.
AB  - Combining sensory inputs over space and time is fundamental to vision. Population
      receptive field models have been successful in characterizing spatial encoding
      throughout the human visual pathways. A parallel question, how visual areas in
      the human brain process information distributed over time, has received less
      attention. One challenge is that the most widely used neuroimaging method, fMRI,
      has coarse temporal resolution compared with the time-scale of neural dynamics.
      Here, via carefully controlled temporally modulated stimuli, we show that
      information about temporal processing can be readily derived from fMRI signal
      amplitudes in male and female subjects. We find that all visual areas exhibit
      subadditive summation, whereby responses to longer stimuli are less than the
      linear prediction from briefer stimuli. We also find fMRI evidence that the
      neural response to two stimuli is reduced for brief interstimulus intervals
      (indicating adaptation). These effects are more pronounced in visual areas
      anterior to V1-V3. Finally, we develop a general model that shows how these
      effects can be captured with two simple operations: temporal summation followed
      by a compressive nonlinearity. This model operates for arbitrary temporal
      stimulation patterns and provides a simple and interpretable set of computations
      that can be used to characterize neural response properties across the visual
      hierarchy. Importantly, compressive temporal summation directly parallels earlier
      findings of compressive spatial summation in visual cortex describing responses
      to stimuli distributed across space. This indicates that, for space and time,
      cortex uses a similar processing strategy to achieve higher-level and
      increasingly invariant representations of the visual world.SIGNIFICANCE STATEMENT
      Combining sensory inputs over time is fundamental to seeing. Two important
      temporal phenomena are summation, the accumulation of sensory inputs over time,
      and adaptation, a response reduction for repeated or sustained stimuli. We
      investigated these phenomena in the human visual system using fMRI. We built
      predictive models that operate on arbitrary temporal patterns of stimulation
      using two simple computations: temporal summation followed by a compressive
      nonlinearity. Our new temporal compressive summation model captures (1)
      subadditive temporal summation, and (2) adaptation. We show that the model
      accounts for systematic differences in these phenomena across visual areas.
      Finally, we show that for space and time, the visual system uses a similar
      strategy to achieve increasingly invariant representations of the visual world.

PMID- 29192129
TI  - Balance your folate or the yin and yang of folate in hematopoiesis.

PMID- 29192128
TI  - Zinc Inhibits TRPV1 to Alleviate Chemotherapy-Induced Neuropathic Pain.
AB  - Zinc is a transition metal that has a long history of use as an anti-inflammatory
      agent. It also soothes pain sensations in a number of animal models. However, the
      effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy
      remain unknown. Here we show that locally injected zinc markedly reduces
      neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy
      drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the
      function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires
      the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm.
      Moreover, TRPA1 is required for zinc-induced inhibition of TRPV1-mediated acute
      nociception. Unexpectedly, zinc transporters, but not TRPA1, are required for
      zinc-induced inhibition of TRPV1-dependent chronic neuropathic pain produced by
      paclitaxel. Together, our study demonstrates a novel mechanism underlying the
      analgesic effect of zinc on paclitaxel-induced neuropathic pain that relies on
      the function of TRPV1.SIGNIFICANCE STATEMENT The chemotherapy-induced peripheral
      neuropathy is a major limiting factor affecting the chemotherapy patients. There
      is no effective treatment available currently. We demonstrate that zinc prevents
      paclitaxel-induced mechanical hypersensitivity via inhibiting the TRPV1 channel,
      which is involved in the sensitization of peripheral nociceptors in chemotherapy.
      Zinc transporters in DRG neurons are required for the entry of zinc into the
      intracellular side, where it inhibits TRPV1. Our study provides insight into the
      mechanism underlying the pain-soothing effect of zinc and suggests that zinc
      could be developed to therapeutics for the treatment of chemotherapy-induced
      peripheral neuropathy.

PMID- 29192130
TI  - Transplantation for therapy-related, TP53-mutated myelodysplastic syndrome - not
      because we can, but because we should.

PMID- 29192131
TI  - Amotosalen/UVA pathogen inactivation technology reduces platelet activability,
      induces apoptosis and accelerates clearance.

PMID- 29192132
TI  - In response to the comment by Hechler et al.: Amotosalen/UVA pathogen
      inactivation technology reduces platelet activatability, induces apoptosis and
      accelerates clearance.

PMID- 29192134
TI  - Poly[n]catenanes: Synthesis of molecular interlocked chains.
AB  - As the macromolecular version of mechanically interlocked molecules, mechanically
      interlocked polymers are promising candidates for the creation of sophisticated
      molecular machines and smart soft materials. Poly[n]catenanes, where the
      molecular chains consist solely of interlocked macrocycles, contain one of the
      highest concentrations of topological bonds. We report, herein, a synthetic
      approach toward this distinctive polymer architecture in high yield (~75%) via
      efficient ring closing of rationally designed metallosupramolecular polymers.
      Light-scattering, mass spectrometric, and nuclear magnetic resonance
      characterization of fractionated samples support assignment of the high-molar
      mass product (number-average molar mass ~21.4 kilograms per mole) to a mixture of
      linear poly[7-26]catenanes, branched poly[13-130]catenanes, and cyclic poly[4
      7]catenanes. Increased hydrodynamic radius (in solution) and glass transition
      temperature (in bulk materials) were observed upon metallation with Zn2.

PMID- 29192133
TI  - Synthetic transcription elongation factors license transcription across
      repressive chromatin.
AB  - The release of paused RNA polymerase II into productive elongation is highly
      regulated, especially at genes that affect human development and disease. To
      exert control over this rate-limiting step, we designed sequence-specific
      synthetic transcription elongation factors (Syn-TEFs). These molecules are
      composed of programmable DNA-binding ligands flexibly tethered to a small
      molecule that engages the transcription elongation machinery. By limiting
      activity to targeted loci, Syn-TEFs convert constituent modules from broad
      spectrum inhibitors of transcription into gene-specific stimulators. Here we
      present Syn-TEF1, a molecule that actively enables transcription across
      repressive GAA repeats that silence frataxin expression in Friedreich's ataxia, a
      terminal neurodegenerative disease with no effective therapy. The modular design
      of Syn-TEF1 defines a general framework for developing a class of molecules that
      license transcription elongation at targeted genomic loci.

PMID- 29192135
TI  - Encephalocraniocutaneous Lipomatosis: Haberland Syndrome.
AB  - BACKGROUND Encephalocraniocutaneous lipomatosis (ECCL) was first announced as a
      new type of ectomesodermal dysgenesis in 1970 by Haberland and Perou. ECCL was
      first described in 1970, and approximately 60 cases have been reported since
      then. The classic triad of ECCL are skin, ocular, and central nervous system
      involvement, including conditions such as unilateral porencephalic cyst,
      ipsilateral lipomatous hamartoma of the scalp-eyelids-eye globe, cortical
      atrophy, cranial asymmetry, developmental delay, seizures, mental retardation,
      and spasticity of the contralateral limbs. The dermatological hallmark is a
      hairless fatty tissue nevus of the scalp called nevus psiloliparus. CASE REPORT
      An 11-year-old right-handed boy, born at full term, was referred to our clinic.
      His family had no consanguinity or history of neurocutaneous disease. The
      patient's physical examination revealed a large hairless lesion on the right
      frontoparietal scalp called nevus psiloliparus. Beginning from the birth, a
      dermolipoma (an uncommon benign tumor) was reported to have occurred on the
      conjunctiva, mostly ipsilateral in his right eye and present on the ipsilateral
      side of the neurological abnormalities shown on magnetic resonance imaging and
      computed tomography. The patient had muscle weakness in left upper and lower
      extremities. He had a mild form of mental retardation. CONCLUSIONS There is no
      specific treatment for ECCL. Management of ECCL is usually symptomatic. Surgical
      correction of a cutaneous lesion can be performed for cosmetic improvement. An
      early diagnosis of ECCL allows for early symptom treatment and improved patient
      quality of life.

PMID- 29192136
TI  - Up-Regulated Maternal Embryonic Leucine Zipper Kinase Predicts Poor Prognosis of
      Hepatocellular Carcinoma Patients in a Chinese Han Population.
AB  - BACKGROUND Maternal embryonic leucine zipper kinase (MELK) has been implicated in
      various types of tumors, but its expression profile and clinicopathologic
      significance in hepatocellular carcinoma (HCC) in Chinese Han people remains
      unknown. Therefore, this study attempted to investigate the expression pattern of
      MELK in HCC tissues obtained from a Chinese Han population. MATERIAL AND METHODS
      The expression of MELK, from RNA to protein levels, in HCC or disease-free human
      liver tissues was evaluated using quantitative real-time polymerase chain
      reaction assays and immunohistochemistry staining, and its prognostic
      significance was determined based on its impact on HCC patients' survival.
      RESULTS We found that HCC tissues expressed a higher level of MELK RNA than non
      tumor tissues in tumor-related public databases (P<0.001). Hence, we assessed
      MELK mRNA expression within 32 HCC samples and their adjacent non-tumorous liver
      tissues in our center. Subsequently, MELK protein expression was evaluated within
      101 HCC specimens and 40 disease-free liver tissues. Notably, it revealed that
      high MELK protein expression was significantly related with tumor number, tumor
      size, higher pathological tumor-nodule-metastasis stage, vascular invasion, and
      recurrence (P<0.05, all). Furthermore, elevated MELK protein expression was
      correlated with decreased overall survival and disease-free survival (P=0.004 and
      P=0.002, respectively). Univariate and multivariate analysis results show that
      MELK protein may serve as an independent prognostic indicator for determining
      prognosis of HCC patients. CONCLUSIONS We found that, in a Chinese Han
      population, MELK was highly expressed within HCC tissues from RNA to protein
      levels, and may be a potential independent prognostic biomarker for HCC patients.

PMID- 29192137
TI  - Application of Fully Covered Self-Expandable Metallic Stents with and without
      Antimigration Waist Versus Repeated Plastic Biliary Stent Placement in Management
      of Anastomotic Biliary Strictures After Orthotopic Liver Transplantation.
AB  - BACKGROUND Standard methods for endoscopic retrograde cholangiopancreatography
      (ERCP) management of anastomotic strictures (AS) after OLT includes repeated
      balloon dilation of the stricture with subsequent insertion of a plastic biliary
      stent (PBS). In post-OLT patients not responding to standard endoscopic
      treatment, the placement of fully covered self-expanding metal stents (FCSEMS) is
      a valid alternative to surgical treatment. The aim of this study was to compare
      the results of new FCSEMS implantation with the standard ERCP stricture
      management protocol and with conventional FCSEMS insertion. MATERIAL AND METHODS
      This retrospective study involved 39 post-OLT patients with confirmed diagnosis
      of biliary AS. Enrolled subjects were divided into 2 groups: the FCSEMS group
      (study group) and the PBS group (control group). The study group was divided into
      2 subgroups: the conventional FCSEMS group and the new-type FCSEMS group. RESULTS
      Stricture recurrence after PBS placement was observed in 36.36% of controls and
      in only 9.52% of study group members (P=0.170). Recurrence rates in patients
      after conventional FCSEMS and new type FCSEMS implantation was similar (10% vs.
      9.09%; P=0.501). The applied treatment was successful in 82.61% of study group
      members and only 43.75% of controls (P=0.029). Success rates of conventional
      FCSEMS and new-type SEMS insertion did not differ significantly (81.82% vs.
      83.33%, P=0.649). There was no statistically significant difference in
      complication rates between groups (P=0.879). CONCLUSIONS Implantation of FCSEMS
      is more effective than repeated balloon dilatation of AS with subsequent PBS
      placement and is they have similar complication rates. Application of new-type
      FCSEMS gives results comparable to conventional FCSEMS.

PMID- 29192138
TI  - Publisher Correction: Multi-orbital charge transfer at highly oriented
      organic/metal interfaces.
AB  - The original version of this Article contained an error in the spelling of the
      author Claus Michael Schneider, which was incorrectly given as Claus Michael
      Schneidery. This has now been corrected in both the PDF and HTML versions of the
      Article.

PMID- 29192139
TI  - BEX1 is an RNA-dependent mediator of cardiomyopathy.
AB  - Regulation of mRNA splicing, processing and stability is increasingly recognized
      as a critical control point in dynamically altering gene expression during stress
      or disease. Very little is understood of this process in heart failure. Here, we
      show that BEX1 is a heart failure-induced gene functioning as an mRNA-associated
      protein that enhances expression of a subset of cardiac disease-promoting genes.
      Modeling the increase in BEX1 that occurs in disease, cardiac-specific BEX1
      transgenic mice show worse cardiac disease with stress stimulation, whereas Bex1
      gene-deleted mice are protected from heart failure-promoting insults. Proteomic
      and interactive screening assays show that BEX1 is part of a large
      ribonucleoprotein processing complex involved in regulating proinflammatory mRNA
      expression in the heart. Specifically, induction of BEX1 augments the stability
      and expression of AU-rich element containing mRNAs typically found within
      proinflammatory genes. Thus, BEX1 functions as an mRNA-dependent effector that
      augments pathology-promoting gene expression during heart failure.

PMID- 29192140
TI  - The gibberellin GID1-DELLA signalling module exists in evolutionarily ancient
      conifers.
AB  - Gibberellins (GAs) participate in controlling various aspects of basic plant
      growth responses. With the exception of bryophytes, GA signalling in land plants,
      such as lycophytes, ferns and angiosperms, is mediated via GIBBERELLIN
      INSENSITIVE DWARF1 (GID1) and DELLA proteins. To explore whether this GID1-DELLA
      mechanism is present in pines, we cloned an orthologue (PtGID1) of Arabidopsis
      AtGID1a and two putative DELLA proteins (PtDPL; PtRGA) from Pinus tabuliformis, a
      widespread indigenous conifer species in China, and studied their recombinant
      proteins. PtGID1 shares with AtGID1a the conserved HSL motifs for GA binding and
      an N-terminal feature that are essential for interaction with DELLA proteins.
      Indeed, A. thaliana 35S:PtGID1 overexpressors showed a strong GA-hypersensitive
      phenotype compared to the wild type. Interactions between PtGID1 and PtDELLAs,
      but also interactions between the conifer-angiosperm counterparts (i.e. between
      AtGID1 and PtDELLAs and between PtGID1 and AtDELLA), were detected in vivo. This
      demonstrates that pine has functional GID1-DELLA components. The Delta17-domains
      within PtDPL and PtRGA were identified as potential interaction sites within
      PtDELLAs. Our results show that PtGID1 has the ability to interact with DELLA and
      functions as a GA receptor. Thus, a GA-GID1-DELLA signalling module also operates
      in evolutionarily ancient conifers.

PMID- 29192141
TI  - Colloidal shuttles for programmable cargo transport.
AB  - The active transport of cargo molecules within cells is essential for life.
      Developing synthetic strategies for cargo control in living or inanimate thermal
      systems could lead to powerful tools to manipulate chemical gradients at the
      microscale and thus drive processes out of equilibrium to realize work. Here we
      demonstrate a colloidal analog of the complex biological shuttles responsible for
      molecular trafficking in cells. Our colloidal shuttles consist of magneto
      dielectric particles that are loaded with cargo particles or living cells through
      size-selective dielectrophoretic trapping using electrical fields. The loaded
      colloidal shuttle can be transported with magnetic field gradients before cargo
      is released at the target location by switching off the electrical field. Such
      spatiotemporal control over the distribution of chemically active cargo in a
      reversible fashion can be potentially exploited for fundamental biological
      research or for the development of novel technologies for advanced cell
      culturing, drug discovery and medical diagnosis.

PMID- 29192142
TI  - Ice nucleation triggered by negative pressure.
AB  - Homogeneous ice nucleation needs supercooling of more than 35 K to become
      effective. When pressure is applied to water, the melting and the freezing points
      both decrease. Conversely, melting and freezing temperatures increase under
      negative pressure, i.e. when water is stretched. This study presents an
      extrapolation of homogeneous ice nucleation temperatures from positive to
      negative pressures as a basis for further exploration of ice nucleation under
      negative pressure. It predicts that increasing negative pressure at temperatures
      below about 262 K eventually results in homogeneous ice nucleation while at
      warmer temperature homogeneous cavitation, i. e. bubble nucleation, dominates.
      Negative pressure occurs locally and briefly when water is stretched due to
      mechanical shock, sonic waves, or fragmentation. The occurrence of such transient
      negative pressure should suffice to trigger homogeneous ice nucleation at large
      supercooling in the absence of ice-nucleating surfaces. In addition, negative
      pressure can act together with ice-inducing surfaces to enhance their intrinsic
      ice nucleation efficiency. Dynamic ice nucleation can be used to improve
      properties and uniformity of frozen products by applying ultrasonic fields and
      might also be relevant for the freezing of large drops in rainclouds.

PMID- 29192143
TI  - Profiling of the transcriptional response to all-trans retinoic acid in breast
      cancer cells reveals RARE-independent mechanisms of gene expression.
AB  - Retinoids, derivatives of vitamin A, are key physiological molecules with
      regulatory effects on cell differentiation, proliferation and apoptosis. As a
      result, they are of interest for cancer therapy. Specifically, models of breast
      cancer have varied responses to manipulations of retinoid signaling. This study
      characterizes the transcriptional response of MDA-MB-231 and MDA-MB-468 breast
      cancer cells to retinaldehyde dehydrogenase 1A3 (ALDH1A3) and all-trans retinoic
      acid (atRA). We demonstrate limited overlap between ALDH1A3-induced gene
      expression and atRA-induced gene expression in both cell lines, suggesting that
      the function of ALDH1A3 in breast cancer progression extends beyond its role as a
      retinaldehyde dehydrogenase. Our data reveals divergent transcriptional responses
      to atRA, which are largely independent of genomic retinoic acid response elements
      (RAREs) and consistent with the opposing responses of MDA-MB-231 and MDA-MB-468
      to in vivo atRA treatment. We identify transcription factors associated with each
      gene set. Manipulation of the IRF1 transcription factor demonstrates that it is
      the level of atRA-inducible and epigenetically regulated transcription factors
      that determine expression of target genes (e.g. CTSS, cathepsin S). This study
      provides a paradigm for complex responses of breast cancer models to atRA
      treatment, and illustrates the need to characterize RARE-independent responses to
      atRA in a variety of models.

PMID- 29192145
TI  - Self-medication by orang-utans (Pongo pygmaeus) using bioactive properties of
      Dracaena cantleyi.
AB  - Animals self-medicate using a variety of plant and arthropod secondary
      metabolites by either ingesting them or anointing them to their fur or skin
      apparently to repel ectoparasites and treat skin diseases. In this respect, much
      attention has been focused on primates. Direct evidence for self-medication among
      the great apes has been limited to Africa. Here we document self-medication in
      the only Asian great ape, orang-utans (Pongo pygmaeus), and for the first time,
      to our knowledge, the external application of an anti-inflammatory agent in
      animals. The use of leaf extracts from Dracaena cantleyi by orang-utan has been
      observed on several occasions; rubbing a foamy mixture of saliva and leaf onto
      specific parts of the body. Interestingly, the local indigenous human population
      also use a poultice of these leaves for the relief of body pains. We present
      pharmacological analyses of the leaf extracts from this species, showing that
      they inhibit TNFalpha-induced inflammatory cytokine production (E-selectin, ICAM
      1, VCAM-1 and IL-6). This validates the topical anti-inflammatory properties of
      this plant and provides a possible function for its use by orang-utans. This is
      the first evidence for the deliberate external application of substances with
      demonstrated bioactive potential for self-medication in great apes.

PMID- 29192144
TI  - Downregulation of myostatin pathway in neuromuscular diseases may explain
      challenges of anti-myostatin therapeutic approaches.
AB  - Muscular dystrophies are characterized by weakness and wasting of skeletal muscle
      tissues. Several drugs targeting the myostatin pathway have been used in clinical
      trials to increase muscle mass and function but most showed limited efficacy.
      Here we show that the expression of components of the myostatin signaling pathway
      is downregulated in muscle wasting or atrophying diseases, with a decrease of
      myostatin and activin receptor, and an increase of the myostatin antagonist,
      follistatin. We also provide in vivo evidence in the congenital myotubular
      myopathy mouse model (knock-out for the myotubularin coding gene Mtm1) that a
      down-regulated myostatin pathway can be reactivated by correcting the underlying
      gene defect. Our data may explain the poor clinical efficacy of anti-myostatin
      approaches in several of the clinical studies and the apparent contradictory
      results in mice regarding the efficacy of anti-myostatin approaches and may
      inform patient selection and stratification for future trials.

PMID- 29192146
TI  - Cardiovascular Disease Risk Assessment in the United States and Low- and Middle
      Income Countries Using Predicted Heart/Vascular Age.
AB  - Almost 80% of the global burden of cardiovascular disease (CVD) occurs in low-
      and middle-income countries (LMICs). However, LMICs do not have well-established,
      low-technology ways to quantify and communicate CVD risk at population or
      individual levels. We examined predicted heart/vascular age (PHA) in six LMICs
      and the United States. Data were from CVD-free adults in World Health
      Organization Study on Global Aging and Adult Health (n = 29094) and US National
      Health and Nutritional Examination Survey (n = 6726). PHA was calculated using
      the non-laboratory Framingham CVD risk equation. High excess PHA (HEPHA) was
      defined as the differences between PHA and chronological age >5 years. Logistic
      regression models were used to identify factors associated with HEPHA. Age
      standardized prevalence of HEPHA was higher in Russia 52%; China 56%; Mexico 59%;
      and South Africa 65% compared to the US 45%, Ghana 36%; and India 38%. In LMICs,
      higher income, being divorced/widowed, alcohol intake and abdominal obesity had
      higher odds of HEPHA; higher education, fruit intake and physical activity had
      lower odds of HEPHA. The use of PHA may offer a useful avenue to communicate CVD
      risk. Interventions tailored at socioeconomic and cultural factors that influence
      CVD risk factors may be necessary to prevent CVD in LMICs.

PMID- 29192147
TI  - Protein crowding and lipid complexity influence the nanoscale dynamic
      organization of ion channels in cell membranes.
AB  - Cell membranes are crowded and complex environments. To investigate the effect of
      protein-lipid interactions on dynamic organization in mammalian cell membranes,
      we have performed coarse-grained molecular dynamics simulations containing >100
      copies of an inwardly rectifying potassium (Kir) channel which forms specific
      interactions with the regulatory lipid phosphatidylinositol 4,5-bisphosphate
      (PIP2). The tendency of protein molecules to cluster has the effect of organizing
      the membrane into dynamic compartments. At the same time, the diversity of lipids
      present has a marked effect on the clustering behavior of ion channels. Sub
      diffusion of proteins and lipids is observed. Protein crowding alters the sub
      diffusive behavior of proteins and lipids such as PIP2 which interact tightly
      with Kir channels. Protein crowding also affects bilayer properties, such as
      membrane undulations and bending rigidity, in a PIP2-dependent manner. This
      interplay between the diffusion and the dynamic organization of Kir channels may
      have important implications for channel function.

PMID- 29192148
TI  - The importance of parameter choice in modelling dynamics of the eye lens.
AB  - The lens provides refractive power to the eye and is capable of altering ocular
      focus in response to visual demand. This capacity diminishes with age. Current
      biomedical technologies, which seek to design an implant lens capable of
      replicating the function of the biological lens, are unable as yet to provide
      such an implant with the requisite optical quality or ability to change the
      focussing power of the eye. This is because the mechanism of altering focus,
      termed accommodation, is not fully understood and seemingly conflicting theories
      require experimental support which is difficult to obtain from the living eye.
      This investigation presents finite element models of the eye lens based on data
      from human lenses aged 16 and 35 years that consider the influence of various
      modelling parameters, including material properties, a wide range of angles of
      force application and capsular thickness. Results from axisymmetric models show
      that the anterior and posterior zonules may have a greater impact on shape change
      than the equatorial zonule and that choice of capsular thickness values can
      influence the results from modelled simulations.

PMID- 29192149
TI  - Transcription factor repertoire in Ashwagandha (Withania somnifera) through
      analytics of transcriptomic resources: Insights into regulation of development
      and withanolide metabolism.
AB  - Transcription factors (TFs) are important regulators of cellular and metabolic
      functions including secondary metabolism. Deep and intensive RNA-seq analysis of
      Withania somnifera using transcriptomic databases provided 3532 annotated
      transcripts of transcription factors in leaf and root tissues, belonging to 90
      different families with major abundance for WD-repeat (174 and 165 transcripts)
      and WRKY (93 and 80 transcripts) in root and leaf tissues respectively, followed
      by that of MYB, BHLH and AP2-ERF. Their detailed comparative analysis with
      Arabidopsis thaliana, Capsicum annum, Nicotiana tabacum and Solanum lycopersicum
      counterparts together gave interesting patterns. However, no homologs for WsWDR
      representatives, LWD1 and WUSCHEL, were observed in other Solanaceae species. The
      data extracted from the sequence read archives (SRA) in public domain databases
      were subjected to re-annotation, re-mining, re-analysis and validation for
      dominant occurrence of WRKY and WD-repeat (WDR) gene families. Expression of
      recombinant LWD1 and WUSCHEL proteins in homologous system led to enhancements in
      withanolide content indicating their regulatory role in planta in the
      biosynthesis. Contrasting expression profiles of WsLWD1 and WsWUSCHEL provided
      tissue-specific insights for their participation in the regulation of
      developmental processes. The in-depth analysis provided first full-spectrum and
      comparative characteristics of TF-transcripts across plant species, in the
      perspective of integrated tissue-specific regulation of metabolic processes
      including specialized metabolism.

PMID- 29192151
TI  - Spatially resolved Raman spectroscopy of defects, strains, and strain
      fluctuations in domain structures of monolayer graphene.
AB  - We report spatially resolved Raman scattering results of polycrystalline
      monolayer graphene films to study the effects of defects, strains, and strain
      fluctuations on the electrical performance of graphene. Two-dimensional Raman
      images of the integrated intensities of the G and D peaks (I G and I D) were used
      to identify the graphene domain boundaries. The domain boundaries were also
      identified using Raman images of I D/I G and I 2D/I G ratios and 2D spectral
      widths. Interestingly, the I D maps showed that the defects within individual
      domains significantly increased for the graphene with large domain size. The
      correlation analysis between the G and 2D peak energies showed that biaxial
      tensile strain was more developed in the graphene with large domain size than in
      the graphene with small domain size. Furthermore, spatial variations in the
      spectral widths of the 2D peaks over the graphene layer showed that strain
      fluctuations were more pronounced in the graphene with large domain size. It was
      observed that the mobility (sheet resistance) was decreased (increased) for the
      graphene with large domain size. The degradation of the electrical transport
      properties of the graphene with large domain size is mainly due to the defects,
      tensile strains, and local strain fluctuations within the individual domains.

PMID- 29192150
TI  - Directed self-assembly of fluorescence responsive nanoparticles and their use for
      real-time surface and cellular imaging.
AB  - Directed self-assemblies in water are known as the most efficient means of
      forming complex higher ordered structures in nature. Here we show a
      straightforward and robust method for particle assembly which utilises the
      amphiphilic tri-block co-polymer poloxamer-188 and a hydrophobic fluorophore as
      the two designer components, which have a built-in ability to convey spatial and
      temporal information about their surroundings to an observer. Templating of
      particle self-assembly is attributed to interactions between the fluorophore and
      hydrophobic segment of the poloxamer. Particle fluorescence in water is quenched
      but can be induced to selectively switch on in response to temperature, surface
      adsorption and cellular uptake. The ability of the particles to dynamically
      modulate emission intensity can be exploited for selective labelling and real
      time imaging of drug crystal surfaces, natural fibres and insulin fibrils, and
      cellular delivery. As particle solutions are easily prepared, further
      applications for this water-based NIR-fluorescent paint are anticipated.

PMID- 29192152
TI  - One small edit for humans, one giant edit for humankind? Points and questions to
      consider for a responsible way forward for gene editing in humans.
AB  - Gene editing, which allows for specific location(s) in the genome to be targeted
      and altered by deleting, adding or substituting nucleotides, is currently the
      subject of important academic and policy discussions. With the advent of
      efficient tools, such as CRISPR-Cas9, the plausibility of using gene editing
      safely in humans for either somatic or germ line gene editing is being considered
      seriously. Beyond safety issues, somatic gene editing in humans does raise
      ethical, legal and social issues (ELSI), however, it is suggested to be less
      challenging to existing ethical and legal frameworks; indeed somatic gene editing
      is already applied in (pre-) clinical trials. In contrast, the notion of altering
      the germ line or embryo such that alterations could be heritable in humans raises
      a large number of ELSI; it is currently debated whether it should even be allowed
      in the context of basic research. Even greater ELSI debates address the potential
      use of germ line or embryo gene editing for clinical purposes, which, at the
      moment is not being conducted and is prohibited in several jurisdictions. In the
      context of these ongoing debates surrounding gene editing, we present herein
      guidance to further discussion and investigation by highlighting three crucial
      areas that merit the most attention, time and resources at this stage in the
      responsible development and use of gene editing technologies: (1) conducting
      careful scientific research and disseminating results to build a solid evidence
      base; (2) conducting ethical, legal and social issues research; and (3)
      conducting meaningful stakeholder engagement, education and dialogue.

PMID- 29192153
TI  - Expanding the phenotype of metabolic cutis laxa with an additional disorder of N
      linked protein glycosylation.

PMID- 29192154
TI  - Publisher Correction: Infused-liquid-switchable porous nanofibrous membranes for
      multiphase liquid separation.
AB  - In Table 1 of this Article, the third row in the furthest right column contains a
      typographical error and should read 'NH', rather than 'NM', corresponding to n
      hexane as the infused liquid.

PMID- 29192155
TI  - Trehalose significantly enhances the recovery of serum and serum exosomal miRNA
      from a paper-based matrix.
AB  - The preservation of nucleic acids from clinical samples is critical to facilitate
      accurate molecular diagnosis. The use of a paper matrix, Flinders Technology
      Associates (FTA) Elute cards, to archive DNA and viral RNA is well-documented.
      However, the feasibility of FTA Elute cards for archiving serum and serum
      exosomal microRNAs (miRNAs) remains unclear. Here, we performed a comprehensive
      evaluation of FTA Elute cards for miRNA storage and recovery in different pre
      analytical conditions. The recovery of serum miRNA dry-spotted on FTA Elute cards
      by direct elution with water at high temperature was poor. However, serum miRNAs
      dry-spotted on the cards were isolated with about 40% yield when using QIAzol
      lysis reagent and recovery was improved remarkably (>80%) upon extraction from
      cards pre-treated with trehalose. miRNAs stored on the cards remained stable at
      room temperature and can be kept for prolonged periods. Furthermore, miRNAs could
      be similarly recovered from serum exosomes dry-spotted on the cards. Importantly,
      when using sera from gastric cancer (GC) patients, the miRNAs were efficiently
      recovered from trehalose pre-treated cards without affecting their
      representation. Collectively, we have demonstrated the potential of FTA Elute
      cards to archive serum and serum exosomal miRNAs, making it useful for biomarker
      discovery and diagnostics.

PMID- 29192156
TI  - Unbiased Quantitative Proteomics Reveals a Crucial Role of the Allergen Context
      for the Activation of Human Dendritic Cells.
AB  - Worldwide, more than 1 billion people suffer from allergic diseases. However,
      until now it is not fully understood how certain proteins can induce allergic
      immune responses, while others cannot. Studies suggest that allergenicity is a
      process not only determined by properties of the allergen itself but also by
      costimulatory factors, that are not classically associated with allergic
      reactions. To investigate the allergenicity of the major birch pollen allergen
      Bet v 1 and the impact of adjuvants associated with pollen, e.g.
      lipopolysaccharide (LPS), we performed quantitative proteome analysis to study
      the activation of monocyte-derived dendritic cells (moDCs). Thus, we treated
      cells with birch pollen extract (BPE), recombinant Bet v 1, and LPS followed by
      proteomic profiling via high-performance liquid chromatography and tandem mass
      spectrometry (HPLC-MS/MS) using isobaric labelling. Enrichment and pathway
      analysis revealed the influence of regulated proteins especially in cytokine
      signalling and dendritic cell activation. We found highly regulated, but
      differentially expressed proteins after treatment with BPE and LPS, whereas the
      cellular response to Bet v 1 was limited. Our findings lead to the conclusion
      that Bet v 1 needs a specific "allergen context" involving cofactors apart from
      LPS to induce an immune response in human moDCs.

PMID- 29192158
TI  - A Copper-Catalyzed Tandem Cyclization Reaction of Aminoalkynes with Alkynes for
      the Construction of Tetrahydropyrrolo[1,2-a]quinolines Scaffold.
AB  - A synthetic method for diversely substituted tetrahydropyrrolo[1,2-a]quinolines
      was developed via CuCl-catalyzed cascade transformation of internal aminoalkynes
      with alkynes under microwave- irradiation.

PMID- 29192157
TI  - Linking functional connectivity and dynamic properties of resting-state networks.
AB  - Spontaneous brain activity is organized into resting-state networks (RSNs)
      involved in internally-guided, higher-order mental functions (default mode,
      central executive and salience networks) and externally-driven, specialized
      sensory and motor processing (auditory, visual and sensorimotor networks). RSNs
      are characterized by their functional connectivity in terms of within-network
      cohesion and between-network integration, and by their dynamic properties in
      terms of synchrony and metastability. We examined the relationship between
      functional connectivity and dynamic network features using fMRI data and an
      anatomically constrained Kuramoto model. Extrapolating from simulated data,
      synchrony and metastability across the RSNs emerged at coupling strengths of 5 <=
      k <= 12. In the empirical RSNs, higher metastability and synchrony were
      respectively associated with greater cohesion and lower integration. Consistent
      with their dual role in supporting both sustained and diverse mental operations,
      higher-order RSNs had lower metastability and synchrony. Sensory and motor RSNs
      showed greater cohesion and metastability, likely to respectively reflect their
      functional specialization and their greater capacity for altering network states
      in response to multiple and diverse external demands. Our findings suggest that
      functional and dynamic RSN properties are closely linked and expand our
      understanding of the neural architectures that support optimal brain function.

PMID- 29192159
TI  - Light and Capillary Waves Propagation in Water Fibers.
AB  - The confinement of light and sound, while they are traveling in fibers, enables a
      variety of light-matter interactions. Therefore, it is natural to ask if fibers
      can also host capillary waves. Capillary waves are similar to those we see when
      throwing a stone into a puddle. Such capillary waves are prohibited in
      microfluidic devices where the liquid is bounded by solid walls. In contrast, we
      have fabricated fibers, which are made entirely from water and are suspended in
      air. The water fiber can therefore move, e.g. in a resonant mode that reassembles
      the motion of a guitar string. In our experiment, light guided through the water
      fiber allows optical interrogation of is capillary oscillations. Co-confining two
      important oscillations in nature: capillary and electromagnetic, might allow a
      new type of devices called Micro-Electro-Capillary-Systems [MECS]. The softness
      of MECS is a million times higher when compared to what the current solid-based
      technology permits, which accordingly improves MECS response to minute forces
      such as small changes in acceleration. Additionally, MECS might allow new ways to
      optically interrogate viscosity and surface tension, as well as their changes
      caused by introducing an analyte into the system.

PMID- 29192160
TI  - A Novel Human Systemic Lupus Erythematosus Model in Humanised Mice.
AB  - Mouse models have contributed to the bulk of knowledge on Systemic Lupus
      Erythematosus (SLE). Nevertheless, substantial differences exist between human
      and mouse immune system. We aimed to establish and characterise a SLE model
      mediated by human immune system. Injection of pristane into immunodeficient mice
      reconstituted with human immune system (humanised mice) recapitulated key SLE
      features, including: production of human anti-nuclear autoantibodies, lupus
      nephritis, and pulmonary serositis. There was a reduction in the number of human
      lymphocytes in peripheral blood, resembling lymphopenia in SLE patients.
      Concurrently, B cells and T cells were systemically hyperactivated, with a
      relative expansion of CD27+ and CD27-IgD- memory B cells, increased number of
      plasmablasts/plasma cells, and accumulation of effector memory T cells. There was
      also an increased production of human pro-inflammatory cytokines, including: IFN
      gamma, IL-8, IL-18, MCP-1, and IL-6, suggesting their role in SLE pathogenesis.
      Increased expression of type I IFN signature genes was also found in human
      hepatocytes. Altogether, we showed an SLE model that was mediated by human immune
      system, and which recapitulated key clinical and immunological SLE features. The
      advancements of humanised mice SLE model would provide an in vivo platform to
      facilitate translational studies and pre-clinical evaluations of human-specific
      mechanisms and immunotherapies.

PMID- 29192161
TI  - Unusual scaling laws for plasmonic nanolasers beyond the diffraction limit.
AB  - Plasmonic nanolasers are a new class of amplifiers that generate coherent light
      well below the diffraction barrier bringing fundamentally new capabilities to
      biochemical sensing, super-resolution imaging, and on-chip optical communication.
      However, a debate about whether metals can enhance the performance of lasers has
      persisted due to the unavoidable fact that metallic absorption intrinsically
      scales with field confinement. Here, we report plasmonic nanolasers with
      extremely low thresholds on the order of 10 kW cm-2 at room temperature, which
      are comparable to those found in modern laser diodes. More importantly, we find
      unusual scaling laws allowing plasmonic lasers to be more compact and faster with
      lower threshold and power consumption than photonic lasers when the cavity size
      approaches or surpasses the diffraction limit. This clarifies the long-standing
      debate over the viability of metal confinement and feedback strategies in laser
      technology and identifies situations where plasmonic lasers can have clear
      practical advantage.

PMID- 29192162
TI  - Environmental conditions limit attractiveness of a complex sexual signal in the
      tungara frog.
AB  - Animals choosing particular display sites often balance sexual and natural
      selection pressures. Here we assess how physical properties of display sites can
      alter this balance by influencing signal production and attractiveness of the
      tungara frog (Physalaemus pustulosus). Males that call from very shallow water
      bodies (few mm depth) benefit from reduced predation risk, but by manipulating
      water levels, we show that this comes at a cost of reduced attractiveness to
      females. Our data show that calling from shallower water reduces a male's ability
      to float, limits the inflation of his vocal sac, and consequently reduces signal
      conspicuousness in terms of amplitude and complexity. Our results demonstrate
      that display site properties can set limits on signal production and
      attractiveness and may hence influence signal evolution. Signallers may shift
      between sites or engineer their display location, which can play a crucial role
      in signal divergence and speciation, particularly in a rapidly changing world.

PMID- 29192163
TI  - Investigating quantum metrology in noisy channels.
AB  - Quantum entanglement lies at the heart of quantum information and quantum
      metrology. In quantum metrology, with a colossal amount of quantum Fisher
      information (QFI), entangled systems can be ameliorated to be a better resource
      scheme. However, noisy channels affect the QFI substantially. This research work
      seeks to investigate how QFI of N-qubit Greenberger-Horne-Zeilinger (GHZ) state
      is affected when subjected to decoherence channels: bit-phase flip (BPF) and
      generalize amplitude damping (GAD) channels, which can be induced experimentally.
      We determine the evolution under these channels, deduce the eigenvalues, and then
      derive the QFI. We found that when there is no interaction with the environment,
      the Heisenberg limit can be achieved via rotations along the z direction. It has
      been shown that in BPF channel, the maximal mean QFI of the N-qubit GHZ state
      ([Formula: see text]) dwindles as decoherence rate (p B ) increases due to flow
      of information from the system to the environment, until p B  = 0.5, then revives
      to form a symmetric around p B  = 0.5. Thus, p B  > 0.5 leads to a situation
      where more noise yields more efficiency. We found that in GAD channel, at finite
      temperature, QFIs decay more rapidly than at zero temperature. Our results also
      reveal that QFI can be enhanced by adjusting the temperature of the environment.

PMID- 29192164
TI  - Low-dose levels of bisphenol A inhibit telomerase via ER/GPR30-ERK signalling,
      impair DNA integrity and reduce cell proliferation in primary PBMC.
AB  - Controversy exists about the human health risk of environmental exposure to
      bisphenol A (BPA). Telomerase activity is emerging both as biomarker and
      contributing factor for age-related diseases. The effects of BPA exposure at 1
      1000 nM on telomerase, DNA integrity and cell proliferation were investigated in
      PBMC from human donors. Telomerase activity was determined by TRAP-ELISA assay
      and mRNA expression by qRT-PCR. Mechanistic studies were carried out on the
      ER/GPR30-ERK pathway using specific inhibitors/antagonists, the comet assay to
      quantify DNA damage and flow cytometry for cell proliferation. 24 h BPA exposure
      inhibited telomerase in a non-monotonic pattern with a peak inhibition of 32% at
      1 nM (p <= 0.01). A significant telomerase inhibition was evident at 1 h after
      exposure with a minimum at 6 h. Elevated levels of DNA damage frequency and
      decrease in cell proliferation were evident upon long-term exposure. The results
      further demonstrate that BPA triggered rapidly an ER/GPR30-ERK transduction
      pathway that leads to decreased telomerase activity in human PBMC. This is the
      first study to demonstrate adverse impact of BPA at levels of current human
      exposure on telomerase in normal cells, mediated by ER/GPR30-ERK. The results
      suggest a potentially harmful influence of BPA on immune cells and should be
      addressed in future studies.

PMID- 29192165
TI  - Fine control of metal concentrations is necessary for cells to discern zinc from
      cobalt.
AB  - Bacteria possess transcription factors whose DNA-binding activity is altered upon
      binding to specific metals, but metal binding is not specific in vitro. Here we
      show that tight regulation of buffered intracellular metal concentrations is a
      prerequisite for metal specificity of Zur, ZntR, RcnR and FrmR in Salmonella
      Typhimurium. In cells, at non-inhibitory elevated concentrations, Zur and ZntR,
      only respond to Zn(II), RcnR to cobalt and FrmR to formaldehyde. However, in
      vitro all these sensors bind non-cognate metals, which alters DNA binding. We
      model the responses of these sensors to intracellular-buffered concentrations of
      Co(II) and Zn(II) based upon determined abundances, metal affinities and DNA
      affinities of each apo- and metalated sensor. The cognate sensors are modelled to
      respond at the lowest concentrations of their cognate metal, explaining
      specificity. However, other sensors are modelled to respond at concentrations
      only slightly higher, and cobalt or Zn(II) shock triggers mal-responses that
      match these predictions. Thus, perfect metal specificity is fine-tuned to a
      narrow range of buffered intracellular metal concentrations.

PMID- 29192166
TI  - Spindle associated membrane protein 1 (Samp1) is required for the differentiation
      of muscle cells.
AB  - Muscles are developed and regenerated in a differentiation process called
      myogenesis, which involves components of the nuclear envelope. We have
      investigated Samp1 (Spindle Associated Membrane Protein 1), a transmembrane
      nuclear envelope protein, which interacts with emerin and lamin A, both of which
      are linked to Emery-Dreifuss muscular dystrophy (EDMD). We found that the levels
      of Samp1 increased seven-fold during differentiation of mouse C2C12 muscle
      progenitor cells. To test if Samp1 could have a role in myogenesis we developed
      stable C2C12 knockdown cell lines expressing short hairpin RNA targeting Samp1
      expression. The Samp1 depleted C2C12 cells displayed normal mobility and normal
      distribution of emerin and lamin A. However, Samp1 depletion increased ERK
      signaling and completely blocked differentiation of C2C12 cells, which failed to
      express myogenic marker proteins and failed to form myotubes. The block in
      myogenesis in Samp1 depleted cells was completely rescued by ectopic expression
      of RNAi resistant human Samp1, showing that Samp1 is required for muscle
      differentiation.

PMID- 29192168
TI  - Investigating disordered many-body system with entanglement in momentum space.
AB  - We study the entanglement in momentum space of the ground state of a disordered
      one-dimensional fermion lattice model with attractive interaction. We observe two
      components in the entanglement spectrum, one of which is related to paired
      fermion entanglement and contributes to the long-range correlation in position
      space. The vanishing point of it indicates the localization phenomenon in the
      ground state of this model. Additionally, by method of entanglement spectrum, we
      provide a new evidence to show the transition of two phases induced by
      interaction, and find that this phase transition is not influenced by the
      disorder. Our result show key characteristics in entanglement for different
      phases in the system, and provide a novel perspective to understand localization
      phenomena.

PMID- 29192167
TI  - Partially native intermediates mediate misfolding of SOD1 in single-molecule
      folding trajectories.
AB  - Prion-like misfolding of superoxide dismutase 1 (SOD1) is associated with the
      disease ALS, but the mechanism of misfolding remains unclear, partly because
      misfolding is difficult to observe directly. Here we study the most misfolding
      prone form of SOD1, reduced un-metallated monomers, using optical tweezers to
      measure unfolding and refolding of single molecules. We find that the folding is
      more complex than suspected, resolving numerous previously undetected
      intermediate states consistent with the formation of individual beta-strands in
      the native structure. We identify a stable core of the protein that unfolds last
      and refolds first, and directly observe several distinct misfolded states that
      branch off from the native folding pathways at specific points after the
      formation of the stable core. Partially folded intermediates thus play a crucial
      role mediating between native and non-native folding. These results suggest an
      explanation for SOD1's propensity for prion-like misfolding and point to possible
      targets for therapeutic intervention.

PMID- 29192169
TI  - Face Dependence of Schottky Barriers Heights of Silicides and Germanides on Si
      and Ge.
AB  - Density functional supercell calculations of the Schottky barrier heights (SBH)
      of metal germanides and silicides on Si or Ge find that these vary with the
      facet, unlike those of elemental metals. In addition, silicides and germanides
      show a stronger dependence of their SBHs on the work function than those of
      elemental metals, as seen experimentally. Both effects are beyond the standard
      metal induced gap states model. NiSi2 is found to have a much lower SBH on n
      Si(100) than on n-Si(111), as seen experimentally. It is shown how such results
      can be used to design lower SBH contacts for n-Ge, which are needed
      technologically. The SBHs of the better behaved Si/silicide interfaces can be
      used to benchmark the behavior of the less well behaved Ge-germanide interfaces
      for this purpose. The dependence of the SBH of epitaxial Pb-Si(111) on its
      reconstruction is also covered.

PMID- 29192170
TI  - Monkeys share the neurophysiological basis for encoding sound periodicities
      captured by the frequency-following response with humans.
AB  - The extraction and encoding of acoustical temporal regularities are fundamental
      for human cognitive auditory abilities such as speech or beat entrainment.
      Because the comparison of the neural sensitivity to temporal regularities between
      human and animals is fundamental to relate non-invasive measures of auditory
      processing to their neuronal basis, here we compared the neural representation of
      auditory periodicities between human and non-human primates by measuring scalp
      recorded frequency-following response (FFR). We found that rhesus monkeys can
      resolve the spectrotemporal structure of periodic stimuli to a similar extent as
      humans by exhibiting a homologous FFR potential to the speech syllable /da/. The
      FFR in both species is robust and phase-locked to the fundamental frequency of
      the sound, reflecting an effective neural processing of the fast-periodic
      information of subsyllabic cues. Our results thus reveal a conserved neural
      ability to track acoustical regularities within the primate order. These findings
      open the possibility to study the neurophysiology of complex sound temporal
      processing in the macaque subcortical and cortical areas, as well as the
      associated experience-dependent plasticity across the auditory pathway in
      behaving monkeys.

PMID- 29192171
TI  - A strategy for effective latent HIV reactivation using subtherapeutic drug doses.
AB  - Cell state switches underlie a plethora of biological phenomena and disease
      treatment strategies. Hence the ability to efficiently switch states in a chosen
      direction is of central importance in a number of scenarios. Increasing the
      concentration of an effector that results in a given switch is often limited by
      side effects. Approaches are thus increasingly sought to bypass these
      constraints, increasing the frequency of state switching without increasing the
      frequency of the side effect. Here, we employ dynamical systems theory to uncover
      a simple strategy as to how to maximize the probability of reactivating latent
      Human immunodeficiency virus (HIV) whilst maintaining minimal side effects. We
      demonstrate that continuous supply of an effector is significantly more likely to
      result in a switch with minimal side effects than the same effector supplied in
      temporally discrete doses. Importantly this continual dosage is likely to occur
      far below the Minimum effective dose at a concentration that has classically been
      thought subtherapeutic. We therefore suggest that in many interventional settings
      there exists potential to reduce drug dose much further than has previously been
      thought possible yet still maintaining efficacy.

PMID- 29192172
TI  - Emergence of Quantum Critical Behavior in Metallic Quantum-Well States of
      Strongly Correlated Oxides.
AB  - Controlling quantum critical phenomena in strongly correlated electron systems,
      which emerge in the neighborhood of a quantum phase transition, is a major
      challenge in modern condensed matter physics. Quantum critical phenomena are
      generated from the delicate balance between long-range order and its quantum
      fluctuation. So far, the nature of quantum phase transitions has been
      investigated by changing a limited number of external parameters such as pressure
      and magnetic field. We propose a new approach for investigating quantum
      criticality by changing the strength of quantum fluctuation that is controlled by
      the dimensional crossover in metallic quantum well (QW) structures of strongly
      correlated oxides. With reducing layer thickness to the critical thickness of
      metal-insulator transition, crossover from a Fermi liquid to a non-Fermi liquid
      has clearly been observed in the metallic QW of SrVO3 by in situ angle-resolved
      photoemission spectroscopy. Non-Fermi liquid behavior with the critical exponent
      alpha = 1 is found to emerge in the two-dimensional limit of the metallic QW
      states, indicating that a quantum critical point exists in the neighborhood of
      the thickness-dependent Mott transition. These results suggest that artificial QW
      structures provide a unique platform for investigating novel quantum phenomena in
      strongly correlated oxides in a controllable fashion.

PMID- 29192173
TI  - Metric clusters in evolutionary games on scale-free networks.
AB  - The evolution of cooperation in social dilemmas in structured populations has
      been studied extensively in recent years. Whereas many theoretical studies have
      found that a heterogeneous network of contacts favors cooperation, the impact of
      spatial effects in scale-free networks is still not well understood. In addition
      to being heterogeneous, real contact networks exhibit a high mean local
      clustering coefficient, which implies the existence of an underlying metric
      space. Here we show that evolutionary dynamics in scale-free networks self
      organize into spatial patterns in the underlying metric space. The resulting
      metric clusters of cooperators are able to survive in social dilemmas as their
      spatial organization shields them from surrounding defectors, similar to spatial
      selection in Euclidean space. We show that under certain conditions these metric
      clusters are more efficient than the most connected nodes at sustaining
      cooperation and that heterogeneity does not always favor-but can even hinder
      cooperation in social dilemmas.

PMID- 29192174
TI  - Long-term climate change in the D-region.
AB  - Controversy exists over the potential effects of long-term increases in
      greenhouse gas concentrations on the ionospheric D-region at 60-90 km altitudes.
      Techniques involving in-situ rocket measurements, remote optical observations,
      and radio wave reflection experiments have produced conflicting results. This
      study reports a novel technique that analyses long-distance subionospheric very
      low frequency radiowave observations of the NAA 24.0 kHz transmitter, Cutler,
      Maine, made from Halley Station, Antarctica, over the period 1971-2016. The
      analysis is insensitive to any changes in the output power of the transmitter,
      compensates for the use of different data logging equipment, and can confirm the
      accuracy of the timing systems operated over the 45 year long record. A ~10%
      reduction in the scale size of the transmitter nighttime interference fringe
      pattern has been determined, taking into account the quasi-11 year solar cycle.
      Subionospheric radiowave propagation modeling suggests that the contraction of
      the interference fringe pattern about the mid-latitude NAA transmitter is due to
      a 3 km reduction in the effective height of the nighttime ionospheric D-region
      over the last 45 years. This is consistent with the effect of enhanced infra-red
      cooling by increasing greenhouse gases.

PMID- 29192175
TI  - Higher Platelet-to-Lymphocyte Ratio Increased the Risk of Sarcopenia in the
      Community-Dwelling Older Adults.
AB  - The platelet-to-lymphocyte ratio (PLR) has been extensively studied in oncologic
      diseases. However, the correlation between PLR and sarcopenia remains unknown. In
      this cross-sectional analysis, we enrolled 3,671 non-institutionalized
      individuals from the National Health and Nutrition Examination Survey (NHANES)
      III (1988-1994) aged >=60 years and whose complete blood counts (CBCs), body
      composition measurements, and related demographic information was available.
      Skeletal muscle mass was assessed using a previously published equation
      (including age, sex, height, and bioelectrical impedance analysis). PLR values
      were estimated based on laboratory data. Multiple linear and logistic regression
      analyses, quartile-based stratified odds ratio comparisons, and trend tests were
      performed. Elevations in serum PLR values were significantly associated with
      sarcopenia status and negatively associated with skeletal muscle index. After
      additionally adjusting for other covariates, the significant negative correlation
      remained; moreover, participants with highest serum PLR values (>=155) had 2.36
      times greater risk of sarcopenia than those with lowest PLR values (<90; odds
      ratio (OR) = 2.36; 95% confidence interval (CI): 1.21-3.31; p < 0.01). Higher PLR
      levels are associated with a greater risk of sarcopenia in geriatric populations.
      Thus, PLR as an inexpensive and easily measurable parameter can be considered as
      an inflammatory biomarker for sarcopenia.

PMID- 29192176
TI  - PGC-1alpha levels correlate with survival in patients with stage III NSCLC and
      may define a new biomarker to metabolism-targeted therapy.
AB  - Lung cancer remains the leading cause of cancer-related death worldwide, with one
      third diagnosed with locally advanced (stage III) disease. Preoperative induction
      chemo-radiotherapy is key for the treatment of these patients, however
      conventional cisplatin based approaches has apparently reached a plateau of
      effectiveness. In the search for new therapies, the targeting of tumor metabolism
      is revealed as an interesting option to improve the patient's responses. Here we
      describe the importance of PGC-1alpha and GAPDH/MT-CO1 ratio levels as surrogates
      of the Warburg effect from a series of 28 stage III NSCLC patients, on PFS, OS
      and PET uptake. Moreover, our results show a great variability between tumors of
      different individuals, ranging from very glycolytic to more OXPHOS-dependent
      tumors, which compromises the success of therapies directed to metabolism. In
      this sense, using 3 different cell lines, we describe the relevance of Warburg
      effect on the response to metabolism-targeted therapies. Specifically, we show
      that the inhibitory effect of metformin on cell viability depends on cell's
      dependence on the OXPHOS system. The results on cell lines, together with the
      results of PGC-1alpha and GAPDH/MT-CO1 as biomarkers on patient's biopsies, would
      point out what type of patients would benefit more from the use of these drugs.

PMID- 29192177
TI  - Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis
      by Driving GC Immune Responses and Activating HSCs in Mice.
AB  - The pathology of schistosome egg-induced liver granuloma, fibrosis and eventually
      liver scarring is complicated. CD4+ helper T (Th) cells play critical roles in
      both host humoral immunity and cellular immunity against parasitic infection and
      immunopathology in schistosomiasis. Follicular helper T (Tfh) cells are another
      specialized subset of Th cells and involved in infectious diseases. However, the
      immune regulatory mechanism of Tfh cells in severe liver pathology of
      schistosomiasis is still poorly understood. In this study, using a S. japonicum
      infected mouse model, we studied the dynamics and effects of Tfh cells in vivo
      and demonstrated that Tfh phenotype molecules ICOS, PD-1 and functional factor IL
      21 were positively correlated with disease development by flow cytometry.
      Meanwhile, our results also showed that Tfh cells enriched in splenic germinal
      center (GC) and promoted B cells producing IgM with the progress of hepatic
      immunopathology by B-T co-culture experiments. More importantly, our data
      indicated that IL-21 contributed to the formation and development of hepatic egg
      granuloma and subsequent fibrosis by driving GC responses and activating HSCs by
      immunohistochemical detection and blocking assay in vitro. Our findings
      contribute to the better understanding of the immunopathogenesis of
      schistosomiasis and have implications for therapeutic intervention of hepatic
      fibrotic diseases.

PMID- 29192178
TI  - Characterisation of porous knitted titanium for replacement of intervertebral
      disc nucleus pulposus.
AB  - Effective restoration of human intervertebral disc degeneration is challenged by
      numerous limitations of the currently available spinal fusion and arthroplasty
      treatment strategies. Consequently, use of artificial biomaterial implant is
      gaining attention as a potential therapeutic strategy. Our study is aimed at
      investigating and characterizing a novel knitted titanium (Ti6Al4V) implant for
      the replacement of nucleus pulposus to treat early stages of chronic
      intervertebral disc degeneration. Specific knitted geometry of the scaffold with
      a porosity of 67.67 +/- 0.824% was used to overcome tissue integration failures.
      Furthermore, to improve the wear resistance without impairing original mechanical
      strength, electro-polishing step was employed. Electro-polishing treatment
      changed a surface roughness from 15.22 +/- 3.28 to 4.35 +/- 0.87 um without
      affecting its wettability which remained at 81.03 +/- 8.5 degrees . Subsequently,
      cellular responses of human mesenchymal stem cells (SCP1 cell line) and human
      primary chondrocytes were investigated which showed positive responses in terms
      of adherence and viability. Surface wettability was further enhanced to super
      hydrophilic nature by oxygen plasma treatment, which eventually caused
      substantial increase in the proliferation of SCP1 cells and primary chondrocytes.
      Our study implies that owing to scaffolds physicochemical and biocompatible
      properties, it could improve the clinical performance of nucleus pulposus
      replacement.

PMID- 29192179
TI  - CMScaller: an R package for consensus molecular subtyping of colorectal cancer
      pre-clinical models.
AB  - Colorectal cancers (CRCs) can be divided into four gene expression-based
      biologically distinct consensus molecular subtypes (CMS). This classification
      provides a potential framework for stratified treatment, but to identify novel
      CMS-drug associations, translation of the subtypes to pre-clinical models is
      essential. The currently available classifier is dependent on gene expression
      signals from the immune and stromal compartments of tumors and fails to identify
      the poor-prognostic CMS4-mesenchymal group in immortalized cell lines, patient
      derived organoids and xenografts. To address this, we present a novel CMS
      classifier based on a filtered set of cancer cell-intrinsic, subtype-enriched
      gene expression markers. This new classifier, referred to as CMScaller,
      recapitulated the subtypes in both in vitro and in vivo models (551 in total).
      Importantly, by analyzing public drug response data from patient-derived
      xenografts and cell lines, we show that the subtypes are predictive of response
      to standard CRC drugs. CMScaller is available as an R package.

PMID- 29192180
TI  - Clinical Application of Artificial Ascites in assisting CT-guided Percutaneous
      Cryoablation of Hepatic Tumors Adjacent to the Gastrointestinal Tract.
AB  - This study was to assess the safety and efficacy of artificial ascitetes in
      assisting CT-guided cryoablation of hepatic tumors adjacent to the
      gastrointestinal (GI) tract. A total of 84 patients with peripheral hepatic
      tumors adjacent to the GI tract, who were treated cryoablation, were included in
      this retrospective study. Of these 84 patients, cryoablation had been performed
      in 39 patients with 41 peripheral hepatic tumors. These were assisted by
      induction artificial ascites while 40 patients with 43 peripheral hepatic tumors
      underwent cryoablation without induction of ascites. The artificial ascites
      separation success rate, the cryoablation technique effectiveness, local tumor
      progression and complications were all evaluated. The results showed that the
      artificial ascites separation success rate for 41 hepatic tumors adjacent to the
      GI tract was 95% (39/41). Technique effectiveness of group I was achieved in 35
      of 43 tumors (81.3%) after follow-up imaging three months after cryoablation. In
      group II, technique effectiveness was achieved in 39 of 41 tumors after follow-up
      imaging three months following cryoablation. No major complications were
      encountered in either of the two groups. Artificial ascites assisting in CT
      guided percutaneous cryoablation is a reliable and effective method for the
      treatment of hepatic tumors adjacent to the GI tract, and it can achieve a fine
      local control of such tumors.

PMID- 29192181
TI  - Raman-Deuterium Isotope Probing for in-situ identification of antimicrobial
      resistant bacteria in Thames River.
AB  - The emergence and widespread distribution of antimicrobial resistant (AMR)
      bacteria has led to an increasing concern with respect to potential environmental
      and public health risks. Culture-independent and rapid identification of AMR
      bacteria in-situ in complex environments is important in understanding the role
      of viable but non-culturable and antibiotic persistent bacteria and in revealing
      potential pathogens without waiting for colony formation. In this study, a
      culture-independent and non-destructive phenotyping approach, so called Raman
      Deuterium Stable Isotope Probing (Raman-DIP), was developed to identify AMR
      bacteria in the River Thames. It is demonstrated that Raman-DIP was able to
      accurately identify resistant and susceptible bacteria within 24 hours. The work
      shows that, in the River Thames, the majority of the bacteria (76 +/- 2%) were
      metabolically active, whilst AMR bacteria to carbenicillin, kanamycin and both
      two antibiotics were 35 +/- 5%, 28 +/- 3%, 25 +/- 1% of the total bacterial
      population respectively. Raman activated cell ejection (RACE) was applied to
      isolate single AMR bacteria for the first time, linking AMR phenotype (reistance
      to antibiotics) and genotype (DNA sequence). The sequences of the RACE sorted
      cells indicate that they were potential human pathogens Aeromonas sp.,
      Stenotrophomonas sp. and an unculturable bacterium. This work demonstrates Raman
      DIP and RACE are effective culture-independent approach for rapid identification
      of AMR bacteria at the single cell level in their natural conditions.

PMID- 29192182
TI  - Precise optical modeling of quantum dots for white light-emitting diodes.
AB  - Quantum dots (QDs)-based white light-emitting diodes (QDs-WLEDs) have been
      attracting numerous attentions in lighting and flat panel display applications,
      by virtue of their high luminous efficacy and excellent color rendering ability.
      However, QDs' key optical parameters including scattering, absorption and
      anisotropy coefficients for optical modeling are still unclear, which are
      severely against the design and optimization of QDs-WLEDs. In this work, we
      proposed a new precise optical modeling approach towards QDs. Optical properties
      of QDs-polymer film were obtained for the first time, by combining double
      integrating sphere (DIS) system measurement with inverse adding doubling (IAD)
      algorithm calculation. The measured results show that the typical scattering,
      absorption and anisotropy coefficients of red emissive QDs are 2.9382 mm-1,
      3.7000 mm-1 and 0.4918 for blue light, respectively, and 1.2490 mm-1, 0.6062 mm-1
      and 0.5038 for red light, respectively. A Monte-Carlo ray-tracing model was set
      up for validation. With a maximum deviation of 1.16%, the simulated values
      quantitatively agree with the experimental results. Therefore, our approach
      provides an effective way for optical properties measurement and precise optical
      modeling of QDs for QDs-WLEDs.

PMID- 29192183
TI  - Prevalence of mutations linked to antimalarial resistance in Plasmodium
      falciparum from Chhattisgarh, Central India: A malaria elimination point of view.
AB  - Antimalarial drug resistance is a major global challenge in malaria control and
      elimination. Mutations in six different genes of Plasmodium falciparum (crt,
      mdr1, dhfr, dhps, ATPase6 and K-13 propeller) that confer resistance to
      chloroquine, sulphadoxine-pyrimethamine and artemisinin-based combination therapy
      were analyzed in samples from Chhattisgarh. Seventy-eight percent of the samples
      were found to have a pfcrt mutation (53% double, 24% triple and 1% single
      mutant), and 59% of pfmdr1 genes were found to have an N86Y mutation. Double
      mutations were recorded in pfdhfr gene among 76% of the samples while only 6% of
      the samples harbored mutant genotypes in pfdhps. No mutation was found in the K
      13 propeller gene, while only one sample showed a mutant genotype for the
      PfATPase6 gene. The Tajima test confirmed that there is no role of evolutionary
      natural selection in drug resistance, and gene pairwise linkage of disequilibrium
      showed significant intragenic association. The high level of pfcrt mutations
      suggests that parasite resistance to chloroquine is almost at a fixed level,
      whereas resistance to SP is evolving in the population and parasites remain
      sensitive to artemisinin derivatives. These findings provide potential
      information and understanding of the evolution and spread of different drug
      resistance alleles in Chhattisgarh.

PMID- 29192184
TI  - Affective emotion increases heart rate variability and activates left
      dorsolateral prefrontal cortex in post-traumatic growth.
AB  - The present study evaluated the activities of heart rate variability (HRV) and
      dorsolateral prefrontal cortex (DLPFC) in response to the presentation of
      affective pictures correlated with posttraumatic growth (PTG) among adults
      exposed to the Tianjin explosion incident. The participants who were directly
      involved in the Tianjin explosions were divided into control, post-traumatic
      stress disorder (PTSD) and PTG group according to the scores of PTSD Checklist
      Civilian Version and PTG Inventory survey. All participants received exposure to
      affective images. Electrocardiogram recording took place during the process for
      the purpose of analyzing HRV. Meanwhile, functional near-infrared spectroscopy
      (fNIRS) was used to measure DLPFC activity through hemodynamic response. Our
      results indicated that, while performing the negative and positive picture
      stimulating, PTG increased both in low and high frequency components of HRV
      compared with the control group, but PTSD was not observed in this phenomenon.
      Moreover, the fNIRS data revealed that PTG had an increased activation in the
      left DLPFC compared to the control in the condition of negative pictures
      stimulating, wheras PTSD showed a higher activation in the right DLPFC while
      receiving positive pictures stimulating. To our knowledge, this is the first
      study which provides the differences between PTSD and PTG in emotional
      regulation.

PMID- 29192185
TI  - Association of circulating progenitor cells with angiotensin II in newly
      diagnosed hypertensive patients.
AB  - Populations of CD34- and VEGFR2-expressing cells are responsible for regeneration
      of damaged endothelium and vascular remodelling. As their quantity and activity
      changes during cardiovascular diseases, they are potentially useful markers of
      cardiovascular health. The aim of our study was to investigate changes of various
      CD34+ and CD34+ VEGFR2+ populations in subjects with newly recognised
      hypertension and to evaluate whether observed alterations are influenced by
      clinical parameters and angiotensin II. Circulating CD34+ and CD34+ VEGFR2+ cells
      were analysed in peripheral blood samples by flow cytometry. Serum levels of
      angiotensin II were determined using immunoenzymatic assay. We discovered
      increased proportions of various CD34+ populations and CD34+ VEGFR2+ c-Kit+ cells
      in newly diagnosed patients. CD34+ cells seem to be influenced by angiotensin II,
      but we did not observe comparable results when populations co-expressing VEGFR2
      were analysed. The quantity of CD34+ VEGFR2+ cells in patients with newly
      recognised primary hypertension ought to be determined by other factors.
      Increased proportions of CD34+ progenitors in blood could comprise compensatory
      mechanism for increased endothelial damage in hypertension.

PMID- 29192187
TI  - An Idealized Method of Simulating Residual Ionospheric Errors in Radio
      Occultation.
AB  - An idealized model is used to simulate radio occultation bending angles and
      residual ionospheric errors. The test results of the proposed simulation method
      agree with those of previous studies that use end-to-end simulation tools. Also,
      a new residual ionospheric error model proposed by Healy and Culverwell (2015) is
      verified in this letter by characterizing the key parameter, kappa. A simple
      model, kappa(a) = A - B * (a - 20)/60, is used to estimate the values of kappa,
      where A and B are constants that indicate the magnitude and variation of the
      values of kappa, respectively, and a represents the impact height. When the
      modelled values of kappa are applied in performing ionospheric corrections, the
      residual ionospheric errors decrease from approximately 5 * 10-8 rad to 1 * 10-9
      rad at a latitude of 40 degrees N during the daytime and at a solar activity
      level of F10.7 = 210. Though the proposed model does not assess other error
      terms, such as those associated with asymmetry and noise, it will likely prove to
      be an effective tool for describing idealized residual ionospheric errors in
      radio occultation, and the features of the kappa values identified in this study
      may be helpful in improving ionospheric correction methods.

PMID- 29192186
TI  - Inverted activity patterns in ventromedial prefrontal cortex during value-guided
      decision-making in a less-is-more task.
AB  - Ventromedial prefrontal cortex has been linked to choice evaluation and decision
      making in humans but understanding the role it plays is complicated by the fact
      that little is known about the corresponding area of the macaque brain. We
      recorded activity in macaques using functional magnetic resonance imaging during
      two very different value-guided decision-making tasks. In both cases ventromedial
      prefrontal cortex activity reflected subjective choice values during decision
      making just as in humans but the relationship between the blood oxygen level
      dependent signal and both decision-making and choice value was inverted and
      opposite to the relationship seen in humans. In order to test whether the
      ventromedial prefrontal cortex activity related to choice values is important for
      decision-making we conducted an additional lesion experiment; lesions that
      included the same ventromedial prefrontal cortex region disrupted normal
      subjective evaluation of choices during decision-making.

PMID- 29192188
TI  - Transient experimental demonstration of an elliptical thermal camouflage device.
AB  - The camouflage phenomenon (invisibility or illusion) of thermodynamics has
      attracted great attentions and many experimental demonstrations have been
      achieved by virtue of simplified approaches or the scattering cancellation.
      However, all of the experiments conducted are limited in the invisibility of
      spheres or two-dimensional (2D) cylinders. An ellipsoid camouflage device with a
      homogenous and isotropic shell is firstly reported based on the idea of the
      neutral inclusion and a 2D elliptical thermal camouflage device is realized by a
      thin-layer cloak of homogeneous isotropic material firstly. The robustness of
      this scheme is validated in both 2D and 3D configurations. The current work may
      provide a new avenue to the control of the thermal signatures and we believe this
      work will broaden the current research and pave a new path to the control of the
      path of the heat transfer.

PMID- 29192189
TI  - Single-shot structural analysis by high-energy X-ray diffraction using an
      ultrashort all-optical source.
AB  - High-energy X-rays (HEX-rays) with photon energies on order of 100 keV have
      attractive characteristics, such as comparably low absorption, high spatial
      resolution and the ability to access inner-shell states of heavy atoms. These
      properties are advantageous for many applications ranging from studies of bulk
      materials to the investigation of materials in extreme conditions. Ultrafast X
      ray diffraction allows the direct imaging of atomic dynamics simultaneously on
      its natural time and length scale. However, using HEX-rays for ultrafast studies
      has been limited due to the lack of sources that can generate pulses of
      sufficiently short (femtosecond) duration in this wavelength range. Here we show
      single-crystal diffraction using ultrashort ~90 keV HEX-ray pulses generated by
      an all-optical source based on inverse Compton scattering. We also demonstrate a
      method for measuring the crystal lattice spacing in a single shot that contains
      only ~105 photons in a spectral bandwidth of ~50% full width at half maximum
      (FWHM). Our approach allows us to obtain structural information from the full X
      ray spectrum. As target we use a cylindrically bent Ge crystal in Laue
      transmission geometry. This experiment constitutes a first step towards
      measurements of ultrafast atomic dynamics using femtosecond HEX-ray pulses.

PMID- 29192191
TI  - Viscous Fingering in Multiport Hele Shaw Cell for Controlled Shaping of Fluids.
AB  - The pursuit of mimicking complex multiscale systems has been a tireless effort
      with many successes but a daunting task ahead. A new perspective to engineer
      complex cross-linked meshes and branched/tree-like structures at different scales
      is presented here. Control over Saffman-Taylor instability which otherwise
      randomly rearranges viscous fluid in a 'lifted Hele-Shaw cell' is proposed for
      the same. The proposed control employs multiple-ports or source-holes in this
      cell, to spontaneously shape a stretched fluid film into a network of well
      defined webs/meshes and ordered multiscale tree-like patterns. Use of multiple
      ports enables exercising strong control to fabricate such structures, in a robust
      and repeated fashion, which otherwise are completely non-characteristic to
      viscous fingering process. The proposed technique is capable of fabricating
      spontaneously families of wide variety of structures over micro and very large
      scale in a period of few seconds. Thus the proposed method forms a solid
      foundation to new pathways for engineering multiscale structures for several
      scientific applications including efficient gas exchange, heat transport, tissue
      engineering, organ-on-chip, and so on. Proposal of multi-port Hele-Shaw cell also
      opens new avenues for investigation of complex multiple finger interactions
      resulting in interesting fluid patterns.

PMID- 29192190
TI  - Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent
      neuropathic pain in mice.
AB  - It is known that transient receptor potential ankyrin 1 (TRPA1) channels,
      expressed by nociceptors, contribute to neuropathic pain. Here we show that TRPA1
      is also expressed in Schwann cells. We found that in mice with partial sciatic
      nerve ligation, TRPA1 silencing in nociceptors attenuated mechanical allodynia,
      without affecting macrophage infiltration and oxidative stress, whereas TRPA1
      silencing in Schwann cells reduced both allodynia and neuroinflammation.
      Activation of Schwann cell TRPA1 evoked NADPH oxidase 1 (NOX1)-dependent H2O2
      release, and silencing or blocking Schwann cell NOX1 attenuated nerve injury
      induced macrophage infiltration, oxidative stress and allodynia. Furthermore, the
      NOX2-dependent oxidative burst, produced by macrophages recruited to the
      perineural space activated the TRPA1-NOX1 pathway in Schwann cells, but not TRPA1
      in nociceptors. Schwann cell TRPA1 generates a spatially constrained gradient of
      oxidative stress, which maintains macrophage infiltration to the injured nerve,
      and sends paracrine signals to activate TRPA1 of ensheathed nociceptors to
      sustain mechanical allodynia.

PMID- 29192192
TI  - Fruit fracture biomechanics and the release of Lepidium didymum pericarp-imposed
      mechanical dormancy by fungi.
AB  - The biomechanical and ecophysiological properties of plant seed/fruit structures
      are fundamental to survival in distinct environments. Dispersal of fruits with
      hard pericarps (fruit coats) encasing seeds has evolved many times independently
      within taxa that have seed dispersal as their default strategy. The mechanisms by
      which the constraint of a hard pericarp determines germination timing in response
      to the environment are currently unknown. Here, we show that the hard pericarp of
      Lepidium didymum controls germination solely by a biomechanical mechanism.
      Mechanical dormancy is conferred by preventing full phase-II water uptake of the
      encased non-dormant seed. The lignified endocarp has biomechanically and
      morphologically distinct regions that serve as predetermined breaking zones. This
      pericarp-imposed mechanical dormancy is released by the activity of common fungi,
      which weaken these zones by degrading non-lignified pericarp cells. We propose
      that the hard pericarp with this biomechanical mechanism contributed to the
      global distribution of this species in distinct environments.

PMID- 29192193
TI  - Alleviation of adverse effects of drought stress on wheat seed germination using
      atmospheric dielectric barrier discharge plasma treatment.
AB  - Atmospheric dielectric barrier discharge (DBD) was attempted to improve the
      resistance of wheat seed to drought stress. Effects of DBD plasma on wheat seed
      germination, seedling growth, osmotic-adjustment products, lipid peroxidation,
      reactive oxygen species (ROS), antioxidant enzyme activity, abscisic acid, and
      drought resistant related genes expression under drought stress were
      investigated. The changes of the wheat seed coat before and after the DBD plasma
      treatment were explored. Experimental results showed that the DBD plasma
      treatment could alleviate the adverse effects of drought stress on wheat seed
      germination and seedling growth; the germination potential and germination rate
      increased by 27.2% and 27.6%, and the root length and shoot length of the wheat
      seedlings also increased. Proline and soluble sugar levels under drought stress
      were improved after the DBD plasma treatment, whereas the malondialdehyde content
      decreased. ROS contents under drought stress were reduced after the DBD plasma
      treatment, whereas the activities of superoxide dismutase, catalase, and
      peroxidase were promoted. DBD plasma treatment promoted abscisic acid generation
      in wheat seedlings, and it also regulated functional gene LEA1 and stimulated
      regulation genes SnRK2 and P5CS to resist drought stress. Etching effect and
      surface modification occurred on the seed coat after the DBD plasma treatment.

PMID- 29192194
TI  - Solution structure and interaction with copper in vitro and in living cells of
      the first BIR domain of XIAP.
AB  - The X-chromosome linked inhibitor of apoptosis (XIAP) is a multidomain
      metalloprotein involved in caspase inhibition and in copper homeostasis. It
      contains three zinc-binding baculoviral IAP repeats (BIR) domains, which are
      responsible for caspase interaction. Recently, it has been suggested that the BIR
      domains can bind copper, however high resolution data on such interaction is
      missing. Here we characterize by NMR the structural properties of BIR1 in
      solution, and the effects of its interaction with copper both in vitro and in
      physiological environments. BIR1 is dimeric in solution, consistent with the X
      ray structure. Cysteine 12, located in the unfolded N-terminal region, has a
      remarkably low redox potential, and is prone to oxidation even in reducing
      physiological environments. Interaction of BIR1 with copper(II) results in the
      oxidation of cysteine 12, with the formation of either an intermolecular
      disulfide bond between two BIR1 molecules or a mixed disulfide bond with
      glutathione, whereas the zinc binding site is not affected by the interaction.

PMID- 29192195
TI  - Repellency of zerumbone identified in Cyperus rotundus rhizome and other
      constituents to Blattella germanica.
AB  - The compounds 1,8-cineole and zerumbone (ZER) from the Cyperus rotundus rhizome
      along with another 11 previously identified rhizome essential oil constituents
      and alpha-humulene, which lacks the only carbonyl group present in ZER, as well
      as binary mixtures of ZER and seven active compounds were tested for repellency
      to male B. germanica. The results were compared to N,N-diethyl-3-methylbenzamide
      (deet). In filter-paper choice tests, ZER was the most repellent compound, and
      alpha-humulene was ineffective, which indicates that the alpha,beta-unsaturated
      carbonyl group of ZER is a prerequisite component for repellency. At 81.5 MUg cm
      2, enhanced repellency was produced by binary mixtures of ZER and 1,8-cineole,
      (+)-dihydrocarvone or (R)-(+)-limonene (70:30, 50:50 and 30:70 ratios by weight).
      These mixtures were very effective against male B. germanica within 24 h and were
      more repellent than a single compound or deet alone. The optimum ZER content was
      determined to be more than 50%. In Ebeling choice box tests at 652.4 MUg cm-2,
      these compounds and deet resulted in complete repellency to intact male B.
      germanica, while they exhibited 35-47% repellency to antennectomized male one.
      Mixtures formulated from the active constituents of the C. rotundus rhizome could
      be useful as potential repellents for controlling B. germanica.

PMID- 29192196
TI  - A robust cell culture system supporting the complete life cycle of hepatitis B
      virus.
AB  - The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the
      hepatitis B virus (HBV) receptor enabled researchers to create hepatoma cell
      lines susceptible to HBV infection. Infection in current systems, however, is
      inefficient and virus fails to spread. Infection efficiency is enhanced by
      treating cells with polyethylene glycol 8000 (PEG) during infection. However,
      this alone does not promote virus spread. Here we show that maintaining PEG in
      culture medium increases the rate of infection by at least one order of
      magnitude, and, most importantly, promotes virus spread. To demonstrate the
      utility of this system, we show that two interferon-stimulated genes (ISGs),
      ISG20 and tetherin, restrict HBV spread in NTCP-expressing hepatoma cells. Thus,
      this protocol can be easily applied to existing cell culture systems to study the
      complete HBV life cycle, including virus spread.

PMID- 29192197
TI  - Interaction of Synthetic Human SLURP-1 with the Nicotinic Acetylcholine
      Receptors.
AB  - Human SLURP-1 is a secreted protein of the Ly6/uPAR/three-finger neurotoxin
      family that co-localizes with nicotinic acetylcholine receptors (nAChRs) and
      modulates their functions. Conflicting biological activities of SLURP-1 at
      various nAChR subtypes have been based on heterologously produced SLURP-1
      containing N- and/or C-terminal extensions. Here, we report the chemical
      synthesis of the 81 amino acid residue human SLURP-1 protein, characterization of
      its 3D structure by NMR, and its biological activity at nAChR subtypes.
      Radioligand assays indicated that synthetic SLURP-1 did not compete with [125I]
      alpha-bungarotoxin (alpha-Bgt) binding to human neuronal alpha7 and Torpedo
      californica muscle-type nAChRs, nor to mollusk acetylcholine binding proteins
      (AChBP). Inhibition of human alpha7-mediated currents only occurred in the
      presence of the allosteric modulator PNU120596. In contrast, we observed robust
      SLURP-1 mediated inhibition of human alpha3beta4, alpha4beta4, alpha3beta2
      nAChRs, as well as human and rat alpha9alpha10 nAChRs. SLURP-1 inhibition of
      alpha9alpha10 nAChRs was accentuated at higher ACh concentrations, indicating an
      allosteric binding mechanism. Our results are discussed in the context of recent
      studies on heterologously produced SLURP-1 and indicate that N-terminal
      extensions of SLURP-1 may affect its activity and selectivity on its targets. In
      this respect, synthetic SLURP-1 appears to be a better probe for structure
      function studies.

PMID- 29192198
TI  - Hydrodenitrogenation of pyridines and quinolines at a multinuclear titanium
      hydride framework.
AB  - Investigation of the hydrodenitrogenation (HDN) of aromatic N-heterocycles such
      as pyridines and quinolines at the molecular level is of fundamental interest and
      practical importance, as this transformation is essential in the industrial
      petroleum refining on solid catalysts. Here, we report the HDN of pyridines and
      quinolines by a molecular trinuclear titanium polyhydride complex. Experimental
      and computational studies reveal that the denitrogenation of a pyridine or
      quinoline ring is easier than the ring-opening reaction at the trinuclear
      titanium hydride framework, which is in sharp contrast with what has been
      reported previously. Hydrolysis of the pyridine-derived nitrogen-free hydrocarbon
      skeleton at the titanium framework with H2O leads to recyclization to afford
      cyclopentadiene with the generation of ammonia, while treatment with HCl gives
      the corresponding linear hydrocarbon products and ammonium chloride. This work
      has provides insights into the mechanistic aspects of the hydrodenitrogenation of
      an aromatic N-heterocycle at the molecular level.

PMID- 29192199
TI  - CRISPR/Cas9-assisted gRNA-free one-step genome editing with no sequence
      limitations and improved targeting efficiency.
AB  - The CRISPR/Cas9 system is a powerful, revolutionary tool for genome editing.
      However, it is not without limitations. There are PAM-free and CRISPR-tolerant
      regions that cannot be modified by the standard CRISPR/Cas9 system, and off
      target activity impedes its broader applications. To avoid these drawbacks, we
      developed a very simple CRISPR/Cas9-assisted gRNA-free one-step (CAGO) genome
      editing technique which does not require the construction of a plasmid to express
      a specific gRNA. Instead, a universal N20 sequence with a very high targeting
      efficiency is inserted into the E. coli chromosome by homologous recombination,
      which in turn undergoes a double-stranded break by CRISPR/Cas9 and induces an
      intra-chromosomal recombination event to accomplish the editing process. This
      technique was shown to be able to edit PAM-free and CRISPR-tolerant regions with
      no off-target effects in Escherichia coli. When applied to multi-locus editing,
      CAGO was able to modify one locus in two days with a near 100% editing
      efficiency. Furthermore, modified CAGO was used to edit large regions of up to
      100 kbp with at least 75% efficiency. Finally, genome editing by CAGO only
      requires a transformation procedure and the construction of a linear donor DNA
      cassette, which was further simplified by applying a modular design strategy.
      Although the technique was established in E. coli, it should be applicable to
      other organisms with only minor modifications.

PMID- 29192200
TI  - CRISPR/Cas9-mediated genome editing in naive human embryonic stem cells.
AB  - The combination of genome-edited human embryonic stem cells (hESCs) and
      subsequent neural differentiation is a powerful tool to study neurodevelopmental
      disorders. Since the naive state of pluripotency has favourable characteristics
      for efficient genome-editing, we optimized a workflow for the CRISPR/Cas9 system
      in these naive stem cells. Editing efficiencies of respectively 1.3-8.4% and 3.8
      19% were generated with the Cas9 nuclease and the D10A Cas9 nickase mutant. Next
      to this, wildtype and genome-edited naive hESCs were successfully differentiated
      to neural progenitor cells. As a proof-of-principle of our workflow, two
      monoclonal genome-edited naive hESCs colonies were obtained for TUNA, a long non
      coding RNA involved in pluripotency and neural differentiation. In these genome
      edited hESCs, an effect was seen on expression of TUNA, although not on neural
      differentiation potential. In conclusion, we optimized a genome-editing workflow
      in naive hESCs that can be used to study candidate genes involved in neural
      differentiation and/or functioning.

PMID- 29192201
TI  - Mechanism in External Field-mediated Trapping of Bacteria Sensitive to Nanoscale
      Surface Chemical Structure.
AB  - Molecular imprinting technique enables the selective binding of nanoscale target
      molecules to a polymer film, within which their chemical structure is
      transcribed. Here, we report the successful production of mixed bacterial
      imprinted film (BIF) from several food poisoning bacteria by the simultaneous
      imprinting of their nanoscale surface chemical structures (SCS), and provide
      highly selective trapping of original micron-scale bacteria used in the
      production process of mixed BIF even for multiple kinds of bacteria in real
      samples. Particularly, we reveal the rapid specific identification of E. coli
      group serotypes (O157:H7 and O26:H11) using an alternating electric field and a
      quartz crystal microbalance. Furthermore, we have performed the detailed
      physicochemical analysis of the specific binding of SCS and molecular recognition
      sites (MRS) based on the dynamic Monte Carlo method under taking into account the
      electromagnetic interaction. The dielectrophoretic selective trapping greatly
      depends on change in SCS of bacteria damaged by thermal treatment, ultraviolet
      irradiation, or antibiotic drugs, which can be well explained by the simulation
      results. Our results open the avenue for an innovative means of specific and
      rapid detection of unknown bacteria for food safety and medicine from a nanoscale
      viewpoint.

PMID- 29192202
TI  - Reassessment of fluctuating dental asymmetry in Down syndrome.
AB  - Fluctuating dental asymmetry (FDA) is a tool to measure developmental stability
      that could be increased in gonosomal aneuploidies. The aim of this study was to
      quantify FDA in individuals with Down syndrome (DS). The study group comprised 40
      individuals with DS, and a control group matched for age and sex was created. The
      target teeth were the maxillary central incisors (11,21), maxillary lateral
      incisors (12,22), maxillary canines (13,23), and maxillary first molars (16,26).
      Dental morphometric variables measured on CBCT images included tooth length,
      crown height, root length, mesio-distal diameter, crown-to-root ratio, vestibular
      palatine diameter, mid mesio-distal diameter, mid buccal-palatal diameter,
      maximum buccal-palatal diameter, and cervical circumference. The FA2 fluctuating
      asymmetry index (Palmer and Strobeck, 1986) was applied. Some discrepancies in
      crown-to-root ratios and root length asymmetry were significantly lower in the DS
      individuals than in controls. Combining the crown-to-root ratio of tooth 11
      versus 21, tooth 12 versus 22, and tooth 13 versus 23, we developed a predictive
      model with a discriminatory power between DS and controls of 0.983. Some dental
      morphometric variables may actually be more stable in DS individuals than in the
      general population. This offers a new perspective on the relationship between
      canalization, fluctuating asymmetry, and aneuploidy.

PMID- 29192203
TI  - Habitat-dependent changes in vigilance behaviour of Red-crowned Crane influenced
      by wildlife tourism.
AB  - The Endangered Red-crowned Crane (Grus japonensis) is one of the most culturally
      iconic and sought-after species by wildlife tourists. Here we investigate how the
      presence of tourists influence the vigilance behaviour of cranes foraging in
      Suaeda salsa salt marshes and S. salsa/Phragmites australis mosaic habitat in the
      Yellow River Delta, China. We found that both the frequency and duration of crane
      vigilance significantly increased in the presence of wildlife tourists. Increased
      frequency in crane vigilance only occurred in the much taller S. salsa/P.
      australis mosaic vegetation whereas the duration of vigilance showed no
      significant difference between the two habitats. Crane vigilance declined with
      increasing distance from wildlife tourists in the two habitats, with a minimum
      distance of disturbance triggering a high degree of vigilance by cranes
      identified at 300 m. The presence of wildlife tourists may represent a form of
      disturbance to foraging cranes but is habitat dependent. Taller P. australis
      vegetation serves primarily as a visual obstruction for cranes, causing them to
      increase the frequency of vigilance behaviour. Our findings have important
      implications for the conservation of the migratory red-crowned crane population
      that winters in the Yellow River Delta and can help inform visitor management.

PMID- 29192204
TI  - Bending and breaking of stripes in a charge ordered manganite.
AB  - In charge-ordered phases, broken translational symmetry emerges from couplings
      between charge, spin, lattice, or orbital degrees of freedom, giving rise to
      remarkable phenomena such as colossal magnetoresistance and metal-insulator
      transitions. The role of the lattice in charge-ordered states remains
      particularly enigmatic, soliciting characterization of the microscopic lattice
      behavior. Here we directly map picometer scale periodic lattice displacements at
      individual atomic columns in the room temperature charge-ordered manganite
      Bi0.35Sr0.18Ca0.47MnO3 using aberration-corrected scanning transmission electron
      microscopy. We measure transverse, displacive lattice modulations of the cations,
      distinct from existing manganite charge-order models. We reveal locally
      unidirectional striped domains as small as ~5 nm, despite apparent
      bidirectionality over larger length scales. Further, we observe a direct link
      between disorder in one lattice modulation, in the form of dislocations and shear
      deformations, and nascent order in the perpendicular modulation. By examining the
      defects and symmetries of periodic lattice displacements near the charge ordering
      phase transition, we directly visualize the local competition underpinning
      spatial heterogeneity in a complex oxide.

PMID- 29192205
TI  - Publisher Correction: A shared Runx1-bound Zbtb16 enhancer directs innate and
      innate-like lymphoid lineage development.
AB  - In the original PDF version of this Article, which was published on 16 October
      2017, the publication date was incorrectly given as 11 October 2017. This has now
      been corrected in the PDF; the HTML version of the paper was correct from the
      time of publication.

PMID- 29192206
TI  - Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar
      ataxia type 1.
AB  - YAP and its neuronal isoform YAPdeltaC are implicated in various cellular
      functions. We found that expression of YAPdeltaC during development, but not
      adulthood, rescued neurodegeneration phenotypes of mutant ataxin-1 knock-in
      (Atxn1-KI) mice. YAP/YAPdeltaC interacted with RORalpha via the second WW domain
      and served as co-activators of its transcriptional activity. YAP/YAPdeltaC formed
      a transcriptional complex with RORalpha on cis-elements of target genes and
      regulated their expression. Both normal and mutant Atxn1 interacted with
      YAP/YAPdeltaC, but only mutant Atxn1 depleted YAP/YAPdeltaC from the RORalpha
      complex to suppress transcription on short timescales. Over longer periods,
      mutant Atxn1 also decreased RORalpha in vivo. Genetic supplementation of
      YAPdeltaC restored the RORalpha and YAP/YAPdeltaC levels, recovered YAP/YAPdeltaC
      in the RORalpha complex and normalized target gene transcription in Atxn1-KI mice
      in vivo. Collectively, our data suggest that functional impairment of
      YAP/YAPdeltaC by mutant Atxn1 during development determines the adult pathology
      of SCA1 by suppressing RORalpha-mediated transcription.

PMID- 29192207
TI  - Discovery of naturally occurring ESR1 mutations in breast cancer cell lines
      modelling endocrine resistance.
AB  - Resistance to endocrine therapy remains a major clinical problem in breast
      cancer. Genetic studies highlight the potential role of estrogen receptor-alpha
      (ESR1) mutations, which show increased prevalence in the metastatic, endocrine
      resistant setting. No naturally occurring ESR1 mutations have been reported in in
      vitro models of BC either before or after the acquisition of endocrine resistance
      making functional consequences difficult to study. We report the first discovery
      of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1
      positive cell lines after acquisition of resistance to long-term-estrogen
      deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations
      were enriched with time, impacted on ESR1 binding to the genome and altered the
      ESR1 interactome. The results highlight the importance and functional consequence
      of these mutations and provide an important resource for studying endocrine
      resistance.

PMID- 29192208
TI  - Endogenous Annexin-A1 Regulates Haematopoietic Stem Cell Mobilisation and
      Inflammatory Response Post Myocardial Infarction in Mice In Vivo.
AB  - Endogenous anti-inflammatory annexin-A1 (ANX-A1) plays an important role in
      preserving left ventricular (LV) viability and function after ischaemic insults
      in vitro, but its long-term cardioprotective actions in vivo are largely unknown.
      We tested the hypothesis that ANX-A1-deficiency exaggerates inflammation,
      haematopoietic stem progenitor cell (HSPC) activity and LV remodelling in
      response to myocardial ischaemia in vivo. Adult ANX - A1 -/- mice subjected to
      coronary artery occlusion exhibited increased infarct size and LV macrophage
      content after 24-48 h reperfusion compared with wildtype (WT) counterparts. In
      addition, ANX - A1 -/- mice exhibited greater expansion of HSPCs and altered
      pattern of HSPC mobilisation 8 days post-myocardial infarction, with increased
      circulating neutrophils and platelets, consistent with increased cardiac
      inflammation as a result of increased myeloid invading injured myocardium in
      response to MI. Furthermore, ANX - A1 -/- mice exhibited significantly increased
      expression of LV pro-inflammatory and pro-fibrotic genes and collagen deposition
      after MI compared to WT counterparts. ANX-A1-deficiency increased cardiac
      necrosis, inflammation, hypertrophy and fibrosis following MI, accompanied by
      exaggerated HSPC activity and impaired macrophage phenotype. These findings
      suggest that endogenous ANX-A1 regulates mobilisation and differentiation of
      HSPCs. Limiting excessive monocyte/neutrophil production may limit LV damage in
      vivo. Our findings support further development of novel ANX-A1-based therapies to
      improve cardiac outcomes after MI.

PMID- 29192209
TI  - Mineral particles stimulate innate immunity through neutrophil extracellular
      traps containing HMGB1.
AB  - Calcium phosphate-based mineralo-organic particles form spontaneously in the body
      and may represent precursors of ectopic calcification. We have shown earlier that
      these particles induce activation of caspase-1 and secretion of IL-1beta by
      macrophages. However, whether the particles may produce other effects on immune
      cells is unclear. Here, we show that these particles induce the release of
      neutrophil extracellular traps (NETs) in a size-dependent manner by human
      neutrophils. Intracellular production of reactive oxygen species is required for
      particle-induced NET release by neutrophils. NETs contain the high-mobility group
      protein B1 (HMGB1), a DNA-binding protein capable of inducing secretion of TNF
      alpha by a monocyte/macrophage cell line and primary macrophages. HMGB1 functions
      as a ligand of Toll-like receptors 2 and 4 on macrophages, leading to activation
      of the MyD88 pathway and TNF-alpha production. Furthermore, HMGB1 is critical to
      activate the particle-induced pro-inflammatory cascade in the peritoneum of mice.
      These results indicate that mineral particles promote pro-inflammatory responses
      by engaging neutrophils and macrophages via signaling of danger signals through
      NETs.

PMID- 29192210
TI  - Low resistance to chytridiomycosis in direct-developing amphibians.
AB  - Host-generalist pathogens sporadically infect naive hosts, potentially triggering
      epizootics. The waterborne fungus Batrachochytrium dendrobatidis (Bd) is linked
      to declines of hundreds of amphibian species with aquatic larvae. Although
      several population declines and extinctions attributed to Bd have been reported
      among cryptic species undergoing direct development away from water,
      epidemiological studies focused on these terrestrial frogs are lacking. Our field
      data support that terrestrial direct-developing hosts are less exposed to Bd
      during their ontogeny than species with aquatic larvae, and thus they might lack
      adaptive responses against waterborne chytrids. Using controlled laboratory
      experiments, we exposed wild-caught amphibian species with terrestrial and
      aquatic life histories to Bd and found that direct developers showed more rapid
      increases in infection loads and experienced higher mortality rates than species
      with aquatic larvae. Our findings provide novel information about host responses
      to generalist pathogens and specifically show that our focal direct developing
      species have low resistance to Bd infections. Finally, our results underscore
      that we should not ignore Bd as a potential threat to direct developing species
      simply because they are less exposed to Bd in nature; instead future amphibian
      conservation plans should include efforts to safeguard hundreds of direct
      developing amphibian species globally.

PMID- 29192211
TI  - Nematic superconducting state in iron pnictide superconductors.
AB  - Nematic order often breaks the tetragonal symmetry of iron-based superconductors.
      It arises from regular structural transition or electronic instability in the
      normal phase. Here, we report the observation of a nematic superconducting state,
      by measuring the angular dependence of the in-plane and out-of-plane
      magnetoresistivity of Ba0.5K0.5Fe2As2 single crystals. We find large twofold
      oscillations in the vicinity of the superconducting transition, when the
      direction of applied magnetic field is rotated within the basal plane. To avoid
      the influences from sample geometry or current flow direction, the sample was
      designed as Corbino-shape for in-plane and mesa-shape for out-of-plane
      measurements. Theoretical analysis shows that the nematic superconductivity
      arises from the weak mixture of the quasi-degenerate s-wave and d-wave components
      of the superconducting condensate, most probably induced by a weak anisotropy of
      stresses inherent to single crystals.

PMID- 29192212
TI  - Immunotherapy: Burning fences.

PMID- 29192215
TI  - High-efficiency grating-couplers: demonstration of a new design strategy.
AB  - We present a simple and practical strategy that allows to design high-efficiency
      grating couplers. The technique is based on the simultaneous apodization of two
      structural parameters: the grating period and the fill-factor, along with the
      optimization of the grating coupler etching depth. Considering a 260 nm Si-thick
      Silicon-on-insulator platform, we numerically demonstrated a coupling efficiency
      of -0.8 dB (83%), well matching the experimental value of -0.9 dB (81%). Thanks
      to the optimized design, these results represent the best performance ever
      reported in the literature for SOI structures without the use of any back
      reflector.

PMID- 29192213
TI  - Differentiation therapy revisited.
AB  - The concept of differentiation therapy emerged from the fact that hormones or
      cytokines may promote differentiation ex vivo, thereby irreversibly changing the
      phenotype of cancer cells. Its hallmark success has been the treatment of acute
      promyelocytic leukaemia (APL), a condition that is now highly curable by the
      combination of retinoic acid (RA) and arsenic. Recently, drugs that trigger
      differentiation in a variety of primary tumour cells have been identified,
      suggesting that they are clinically useful. This Opinion article analyses the
      basis for the clinical successes of RA or arsenic in APL by assessing the
      respective roles of terminal maturation and loss of self-renewal. By reviewing
      other successful examples of drug-induced tumour cell differentiation, novel
      approaches to transform differentiating drugs into more efficient therapies are
      proposed.

PMID- 29192214
TI  - Ribosome biogenesis in cancer: new players and therapeutic avenues.
AB  - The ribosome is a complex molecular machine composed of numerous distinct
      proteins and nucleic acids and is responsible for protein synthesis in every
      living cell. Ribosome biogenesis is one of the most multifaceted and energy-
      demanding processes in biology, involving a large number of assembly and
      maturation factors, the functions of which are orchestrated by multiple cellular
      inputs, including mitogenic signals and nutrient availability. Although causal
      associations between inherited mutations affecting ribosome biogenesis and
      elevated cancer risk have been established over the past decade, mechanistic data
      have emerged suggesting a broader role for dysregulated ribosome biogenesis in
      the development and progression of most spontaneous cancers. In this Opinion
      article, we highlight the most recent findings that provide new insights into the
      molecular basis of ribosome biogenesis in cancer and offer our perspective on how
      these observations present opportunities for the design of new targeted cancer
      treatments.

PMID- 29192217
TI  - Decreased miRNA expression in Klinefelter syndrome.
AB  - The widelyvariable phenotypic spectrum and the different severity of symptoms in
      men with Klinefelter syndrome (KS) suggest a role for epigenetic mediators.
      Therefore, the aim of this study is to evaluate the possible involvement of
      miRNAs in the clinical manifestations of KS. To accomplish this, we performed a
      transcriptome analysis in peripheral blood mononuclear cells (PBMCs) of 10 non
      mosaic KS patients, 10 aged-matched healthy men and 10 aged-matched healthy
      female controls with normal karyotype. After RNA extraction from PBMC and the
      preparation of RNA libraries, the samples were sequenced using next generation
      high-throughput sequencing technology. Expression profiling analysis revealed a
      significant differential expression of 2 miRNAs in KS compared to male controls.
      In particular, MIR3648 resulted significantly (q-value < 0.0001) down-regulated
      by -19.084- fold, while MIR3687was strongly down-regulated (q-value < 0.0001)
      considering KS patients. These results were confirmed by qRT-PCR. The functional
      analysis of the two transcripts showed that they seem to play a role in breast
      cancer, hemopoietic abnormalities, immune defects and adipocyte differentiation
      and fat cell maturation. Therefore, we speculate that both miRNAs may play a role
      in the immune and metabolic disorders and in the risk of breast cancer
      development in men with KS.

PMID- 29192216
TI  - BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency.
AB  - Persistent latent reservoir in resting CD4+ T cells is a major obstacle in curing
      HIV-1 infection. Effective strategies for eradication of the HIV-1 reservoir are
      urgently needed. We report here for the first time that two BET inhibitors, RVX
      208, which has entered phase II clinical trials for diverse cardiovascular
      disorders, and PFI-1, which has been widely studied in oncology, can reactivate
      HIV-1 from latency. RVX-208 and PFI-1 treatment alone or in combination with
      other latency reversing agents efficiently reactivated HIV-1 transcription
      through an up-regulation of P-TEFb by increasing CDK9 Thr-186 phosphorylation in
      latently infected Jurkat T cells in vitro. The two BET inhibitors also
      reactivated HIV-1 transcription in cART treated patient-derived resting CD4+ T
      cells ex vivo, without influence on global immune cell activation. Our findings,
      in combination with previous reports, further confirm that BET inhibitors are a
      group of leading compounds for combating HIV-1 latency for viral eradication.

PMID- 29192218
TI  - Magnesium uptake by connecting fluid-phase endocytosis to an intracellular
      inorganic cation filter.
AB  - Cells acquire free metals through plasma membrane transporters. But, in natural
      settings, sequestering agents often render metals inaccessible to transporters,
      limiting metal bioavailability. Here we identify a pathway for metal acquisition,
      allowing cells to cope with this situation. Under limited bioavailability of
      Mg2+, yeast cells upregulate fluid-phase endocytosis and transfer solutes from
      the environment into their vacuole, an acidocalcisome-like compartment loaded
      with highly concentrated polyphosphate. We propose that this anionic inorganic
      polymer, which is an avid chelator of Mg2+, serves as an immobilized cation
      filter that accumulates Mg2+ inside these organelles. It thus allows the vacuolar
      exporter Mnr2 to efficiently transfer Mg2+ into the cytosol. Leishmania parasites
      also employ acidocalcisomal polyphosphate to multiply in their Mg2+-limited
      habitat, the phagolysosomes of inflammatory macrophages. This suggests that the
      pathway for metal uptake via endocytosis, acidocalcisomal polyphosphates and
      export into the cytosol, which we term EAPEC, is conserved.

PMID- 29192220
TI  - Study of the lithium diffusion properties and high rate performance of TiNb6O17
      as an anode in lithium secondary battery.
AB  - TiNb6O17 and TiNb2O7 were synthesized using a solid-state method. The techniques
      were used to assess the electrochemical performance and lithium diffusion
      kinetics of TiNb6O17 related to the unit cell volume with TiNb2O7. The charge
      discharge curves and cyclic voltammetry revealed TiNb6O17 to have a similar redox
      potential to TiNb2O7 as well as a high discharge capacity. The rate performance
      of TiNb6O17 was measured using a rate capability test. SSCV and EIS showed that
      TiNb6O17 had higher lithium diffusion coefficients during the charging. From
      GITT, the lithium diffusion coefficients at the phase transition region showed
      the largest increase from TiNb2O7 to TiNb6O17.

PMID- 29192219
TI  - Symbionts protect aphids from parasitic wasps by attenuating herbivore-induced
      plant volatiles.
AB  - Plants respond to insect attack by releasing blends of volatile chemicals that
      attract their herbivores' specific natural enemies, while insect herbivores may
      carry endosymbiotic microorganisms that directly improve herbivore survival after
      natural enemy attack. Here we demonstrate that the two phenomena can be linked.
      Plants fed upon by pea aphids release volatiles that attract parasitic wasps, and
      the pea aphid can carry facultative endosymbiotic bacteria that prevent the
      development of the parasitic wasp larva and thus markedly improve aphid survival
      after wasp attack. We show that these endosymbionts also attenuate the systemic
      release of volatiles by plants after aphid attack, reducing parasitic wasp
      recruitment and increasing aphid fitness. Our results reveal a novel mechanism
      through which symbionts can benefit their hosts and emphasise the importance of
      considering the microbiome in understanding insect ecological interactions.

PMID- 29192221
TI  - A combined experimental and theoretical investigation on cellular blebbing.
AB  - Although accumulating evidence has demonstrated the important role of membrane
      blebbing in various cellular processes, the fundamental question of how the
      initiation/evolution of blebs are influenced by physical factors like membrane
      cortex interactions and intracellular pressure remains unclear. Here, we report a
      combined modeling and experimental study to address this outstanding issue.
      Specifically, boundary integral method was used to track the motion of membrane
      (in 3D) during blebbing while possible rupture of the bilayer-cortex adhesion has
      also been taken into account. We showed that, for a given differential pressure
      across the cell membrane, the size of the weakened cortex must be over a critical
      value for blebbing to occur and the steady-state volume of a bleb is proportional
      to its initial growth rate, all in good agreement with recent experiments. The
      predicted shape evolution of blebs also matches well with our observations.
      Finally, a blebbing map, summarizing the essential physics involved, was obtained
      which exhibits three distinct regimes: no bleb formation corresponding to a low
      intracellular pressure or a small weakened cortex region; bleb formed with a
      fixed width when the disrupted cortex zone is very large; and a growing bleb
      resulted from progressive membrane-cortex detachment under intermediate weakened
      cortex size.

PMID- 29192222
TI  - Roller-Induced Bundling of Long Silver Nanowire Networks for Strong Interfacial
      Adhesion, Highly Flexible, Transparent Conductive Electrodes.
AB  - Silver nanowires (AgNWs) have been the most promising electrode materials for
      fabrication of flexible transparent touch panel, displays and many other
      electronics because of their excellent electrical properties, cost effectiveness,
      synthesis scalability, and suitability for mass production. Although a few
      literature reports have described the use of short Ag NWs in fabrication of
      randomly oriented Ag NW network-based electrode, their electrical conductivities
      are still far lower than that of Ag films. So far, no any literature report was
      able to provide any simple solution to fabrication of large-area and mass
      manufactural ability to address the issues, such as, conductivity, transparency,
      electrical current withstand, bending stability, and interfacial adhesion. In the
      current work, we provide a simple solution to conquer the above-mentioned
      challenges, and report the development of long Ag NW bundle network electrodes on
      large area PET films that were coated, aligned, and bundled quickly and simply
      using a steel roller. Our developed AgNWs-bundle networks had superior
      performance in optoelectronic properties (sheet resistance 5.8 Omega sq-1;
      optical transmittance 89% at 550 nm wavelength), electrical current withstand up
      to 500 mA, and bending stability over 5000 bending cycles, and strong interfacial
      adhesion.

PMID- 29192223
TI  - Predictors of Atrial Fibrillation Recurrence after Catheter Ablation: Data from
      the German Ablation Registry.
AB  - Catheter ablation (CA) for atrial fibrillation (AF) has emerged as a widespread
      first or second line treatment option. However, up to 45% of patients (pts) show
      recurrence of AF within 12 month after CA. We present prospective multicenter
      registry data comparing characteristics of pts with and without recurrence of AF
      within the first year after CA. This study comprises all pts with complete follow
      up one year after CA (1-y-FU; n = 3679). During 1y-FU in 1687 (45.9%) pts
      recurrence of AF occurred. The multivariate analysis revealed female sex and AF
      type prior to the procedure as predictors for AF recurrence. Furthermore,
      comorbidities such as valvular heart disease and renal failure as well as an
      early AF relapse were also predictors of AF recurrence during 1-y-FU. However,
      despite an AF recurrence rate of 45.9%, the majority of these pts (72.4%)
      reported a significant alleviation of clinical symptoms. In conclusion in pts
      with initially successful CA for AF female sex, AF type, in-hospital AF relapse
      and comorbidities such as renal failure and valvular heart disease are
      independent predictors for AF recurrence during 1-y-FU. However, the majority of
      pts deemed their interventions as successful with significant reduction of
      symptoms irrespective of AF.

PMID- 29192224
TI  - Conserved RNA structures in the intergenic regions of ambisense viruses.
AB  - Ambisense viruses are negative-sense single-stranded RNA viruses that use a
      unique expression strategy. Their genome contains at least one ambisense RNA
      segment that carries two oppositely oriented reading frames separated by an
      intergenic region. It is believed that a structural RNA element within the
      intergenic region is involved in transcription termination. However, a general
      overview over the structural repertoire of ambisense intergenic regions is
      currently lacking. In this study we investigated the structural potential of the
      intergenic regions of all known ambisense viruses and compared their structural
      repertoire by structure-guided clustering. Intergenic regions of most ambisense
      viruses possess a high potential to build stable secondary structures and many
      viruses share common structural motifs in the intergenic regions of their
      ambisense segments. We demonstrate that (i) within the phylogenetic virus groups
      sets of conserved functional structures are present, but that (ii) between the
      groups conservation is low to non-existent. These results reflect a high degree
      of freedom to regulate ambisense transcription termination and also imply that
      the genetic strategy of having an ambisense RNA genome has evolved several times
      independently.

PMID- 29192225
TI  - Tunneling nanotubes (TNT) mediate long-range gap junctional communication:
      Implications for HIV cell to cell spread.
AB  - Cell-to-cell communication is essen for the development of multicellular systems
      and is coordinated by soluble factors, exosomes, gap junction (GJ) channels, and
      the recently described tunneling nanotubes (TNTs). We and others have
      demonstrated that TNT-like structures are mostly present during pathogenic
      conditions, including HIV infection. However, the nature, function, and
      communication properties of TNTs are still poorly understood. In this manuscript,
      we demonstrate that TNTs induced by HIV infection have functional GJs at the ends
      of their membrane extensions and that TNTs mediate long-range GJ communication
      during HIV infection. Blocking or reducing GJ communication during HIV infection
      resulted in aberrant TNT cell-to-cell contact, compromising HIV spread and
      replication. Thus, TNTs and associated GJs are required for the efficient cell-to
      cell communication and viral spread. Our data indicate that targeting TNTs/GJs
      may provide new therapeutic opportunities for the treatment of HIV.

PMID- 29192226
TI  - Transcriptomics reveal an integrative role for maternal thyroid hormones during
      zebrafish embryogenesis.
AB  - Thyroid hormones (THs) are essential for embryonic brain development but the
      genetic mechanisms involved in the action of maternal THs (MTHs) are still
      largely unknown. As the basis for understanding the underlying genetic mechanisms
      of MTHs regulation we used an established zebrafish monocarboxylic acid
      transporter 8 (MCT8) knock-down model and characterised the transcriptome in
      25hpf zebrafish embryos. Subsequent mapping of differentially expressed genes
      using Reactome pathway analysis together with in situ expression analysis and
      immunohistochemistry revealed the genetic networks and cells under MTHs
      regulation during zebrafish embryogenesis. We found 4,343 differentially
      expressed genes and the Reactome pathway analysis revealed that TH is involved in
      1681 of these pathways. MTHs regulated the expression of core developmental
      pathways, such as NOTCH and WNT in a cell specific context. The cellular
      distribution of neural MTH-target genes demonstrated their cell specific action
      on neural stem cells and differentiated neuron classes. Taken together our data
      show that MTHs have a role in zebrafish neurogenesis and suggest they may be
      involved in cross talk between key pathways in neural development. Given that the
      observed MCT8 zebrafish knockdown phenotype resembles the symptoms in human
      patients with Allan-Herndon-Dudley syndrome our data open a window into
      understanding the genetics of this human congenital condition.

PMID- 29192228
TI  - Inhibition of litter decomposition of two emergent macrophytes by addition of
      aromatic plant powder.
AB  - Aromatic plants show antimicrobial activity due to their essential oils, but
      their effect on litter decomposition is unclear. In this study, we evaluated the
      biomass loss and nutrient dynamics in leaf litters of two macrophytes (Miscanthus
      sacchariflorus and Carex brevicuspis) with and without addition of powdered
      material of the aromatic plant Polygonum hydropiper or the non-aromatic plant C.
      brevicuspis. The two powders had similar basic chemical qualities but P.
      hydropiperi had a higher essential oils concentration. Leaf litters of M.
      sacchariflorus and C. brevicuspis were incubated with powdered P. hydropiper or
      C. brevicuspis (500 g m-3, 250 g m-3, and no addition) for 120 days in a mesocosm
      experiment. Compared with the control (no addition), P. hydropiperi addition
      decelerated nutrient release and litter decomposition, while C. brevicuspis
      addition accelerated those processes. The nitrogen concentrations in both leaf
      litters and the phosphorus concentration in C. brevicuspis leaf litter were
      increased by addition of both plant powders. The fungal biomass in both leaf
      litters decreased after P. hydropiperi addition, due to the antifungal activity
      of its essential oils. These data indicate that the aromatic plant P. hydropiperi
      inhibits litter decomposition via its essential oils and that such inhibition is
      not species-specific.

PMID- 29192229
TI  - Seasonal Expression of Oxytocin and Oxytocin Receptor in the Scented Gland of
      Male Muskrat (Ondatra zibethicus).
AB  - Oxytocin (OT) can modulate multiple physiological functions via binding to the
      widely distributed oxytocin receptor (OTR). In this study, we investigated the
      seasonal expressions of OT, OTR and extracellular signal regulated kinase
      (ERK1/2) signaling pathway components in the scented gland of muskrat during the
      breeding and non-breeding seasons. Histologically, glandular cells, interstitial
      cells and excretory tubules were identified in the breeding season scented
      glands, whereas epithelial cells were sparse in the non-breeding season.
      Immunohistochemical results showed that OTR was present in epithelial cells and
      interstitial cells while OT, pERK1/2, ERK1/2 and c-fos were expressed in
      epithelial cells and glandular cells. The protein and mRNA expressions of OTR, OT
      and c-fos were significantly higher in the scented gland in the breeding season
      than in the non-breeding season. Importantly, the levels of OT in scented glands
      and serum were measured by hormone assays, and their concentrations were both
      significantly higher in the breeding season than in the non-breeding season.
      Moreover, bioinformatics analysis showed that the predicted targets of the
      differentially expressed microRNAs might include the genes encoding OTR, ERK1/2
      and c-fos. These findings suggested that OT may regulate the function of muskrat
      scented glands by the locally expressed receptors.

PMID- 29192227
TI  - Conservation of Nonsense-Mediated mRNA Decay Complex Components Throughout
      Eukaryotic Evolution.
AB  - Nonsense-mediated mRNA decay (NMD) is an essential eukaryotic process regulating
      transcript quality and abundance, and is involved in diverse processes including
      brain development and plant defenses. Although some of the NMD machinery is
      conserved between kingdoms, little is known about its evolution. Phosphorylation
      of the core NMD component UPF1 is critical for NMD and is regulated in mammals by
      the SURF complex (UPF1, SMG1 kinase, SMG8, SMG9 and eukaryotic release factors).
      However, since SMG1 is reportedly missing from the genomes of fungi and the plant
      Arabidopsis thaliana, it remains unclear how UPF1 is activated outside the
      metazoa. We used comparative genomics to determine the conservation of the NMD
      pathway across eukaryotic evolution. We show that SURF components are present in
      all major eukaryotic lineages, including fungi, suggesting that in addition to
      UPF1 and SMG1, SMG8 and SMG9 also existed in the last eukaryotic common ancestor,
      1.8 billion years ago. However, despite the ancient origins of the SURF complex,
      we also found that SURF factors have been independently lost across the Eukarya,
      pointing to genetic buffering within the essential NMD pathway. We infer an
      ancient role for SURF in regulating UPF1, and the intriguing possibility of
      undiscovered NMD regulatory pathways.

PMID- 29192230
TI  - Multi-scale magnetic mapping of serpentinite carbonation.
AB  - Peridotite carbonation represents a critical step within the long-term carbon
      cycle by sequestering volatile CO2 in solid carbonate. This has been proposed as
      one potential pathway to mitigate the effects of greenhouse gas release. Most of
      our current understanding of reaction mechanisms is based on hand specimen and
      laboratory-scale analyses. Linking laboratory-scale observations to field scale
      processes remains challenging. Here we present the first geophysical
      characterization of serpentinite carbonation across scales ranging from km to sub
      mm by combining aeromagnetic observations, outcrop- and thin section-scale
      magnetic mapping. At all scales, magnetic anomalies coherently change across
      reaction fronts separating assemblages indicative of incipient, intermittent, and
      final reaction progress. The abundance of magnetic minerals correlates with
      reaction progress, causing amplitude and wavelength variations in associated
      magnetic anomalies. This correlation represents a foundation for characterizing
      the extent and degree of in situ ultramafic rock carbonation in space and time.

PMID- 29192231
TI  - Regulation of ethylene-responsive SlWRKYs involved in color change during tomato
      fruit ripening.
AB  - WRKY transcription factors (TFs) play important roles in stress responses in
      planta. However, the function of WRKY TFs in the regulation of fruit ripening is
      unclear. Here, 23 tomato SlWRKYs that are similar to ethylene-responsive WRKY
      genes from other plant species, or show up-regulation during fruit ripening in
      previous genome-wide study, were selected, and their function in fruit ripening
      was investigated. Twelve SlWRKYs were found to be responsive to ethylene (SlER
      WRKYs), showing expression patterns similar to those of genes related to fruit
      ripening. Eight SlER-WRKYs-SlWRKY16, 17, 22, 25, 31, 33, 53, and 54, detected in
      the nuclei-interacted with and activated the promoters of 4 genes related to
      color change: Pheophytin Pheophorbide Hydrolase (SlPPH), Pheophorbide a Oxygenase
      (SlPAO), Phytoene Synthase 1 (SlPSY1) and Phytoene Desaturase (SlPDS). Yeast two
      hybrid and bimolecular fluorescence complement (BiFC) assays in Arabidopsis
      protoplasts indicated that protein interactions occurred between SlWRKY17 and
      SlRIN, SlERF2b or SlERF7; SlWRKY33 and SlERF7; SlWRKY54 and SlERF2b; and SlWRKY16
      and SlWRKY17. Suppression of SlWRKY 16, 17, 53 or 54 by virus-induced gene
      silencing (VIGS) retarded the red coloration of the fruit. Our study provides
      comprehensive molecular evidence that WRKY TFs function in fruit ripening,
      particularly in color change, and are linked to the intricate regulatory network
      of other ripening regulators.

PMID- 29192232
TI  - Thin single crystal perovskite solar cells to harvest below-bandgap light
      absorption.
AB  - The efficiency of perovskite solar cells has surged in the past few years, while
      the bandgaps of current perovskite materials for record efficiencies are much
      larger than the optimal value, which makes the efficiency far lower than the
      Shockley-Queisser efficiency limit. Here we show that utilizing the below-bandgap
      absorption of perovskite single crystals can narrow down their effective optical
      bandgap without changing the composition. Thin methylammonium lead triiodide
      single crystals with tuned thickness of tens of micrometers are directly grown on
      hole-transport-layer covered substrates by a hydrophobic interface confined
      lateral crystal growth method. The spectral response of the methylammonium lead
      triiodide single crystal solar cells is extended to 820 nm, 20 nm broader than
      the corresponding polycrystalline thin-film solar cells. The open-circuit voltage
      and fill factor are not sacrificed, resulting in an efficiency of 17.8% for
      single crystal perovskite solar cells.

PMID- 29192233
TI  - Kaempferide Prevents Titanium Particle Induced Osteolysis by Suppressing JNK
      Activation during Osteoclast Formation.
AB  - Kaempferide (KF) is an O-methylated flavonol, a natural plant extract, which is
      often found in Kaempferia galanga. It has a variety of effects including anti
      carcinogenic, anti-inflammatory, anti-oxidant, anti-bacterial and anti-viral
      properties. In this study, we aimed to investigate whether KF effectively
      inhibits titanium particle induced calvarial bone loss via down regulation of the
      JNK signaling pathway. In the mice with titanium particle induced calvarial
      osteolysis, the Low dose of KF mildly reduced the resorption pits while in the
      high dose group, fewer scattered pits were observed on the surface of calvarium.
      Histological examination showed fewer osteoclasts formation in the KF group. In
      mouse bone marrow macrophages (BMMs) and RAW264.7 cells, KF significantly
      inhibited the osteoclast formation and bone resorption at 12.5 MUM. However, KF
      does not affect the mature osteoclast F-actin ring formation. But when being co
      treated with KF and anisomycin, BMMs differentiated into mature osteoclasts. At
      the molecular levels, the JNK phosphorylation was inhibited and the
      osteoclastogenesis-related specific gene expression including V-ATPase d2, TRAP,
      calcitonin receptor (CTR), c-Fos and NFATc1 was markedly suppressed. In
      conclusion, these results indicated that KF is a promising agent in the treatment
      of osteoclast-related diseases.

PMID- 29192234
TI  - Architectural diversity and galling insects on Caryocar brasiliense trees.
AB  - Galling insects are a highly sophisticated herbivore group on Caryocar
      brasiliense, a tree that represents the main income source for many communities.
      The effect of architectural diversity of C. brasiliense trees on galling insect
      community diversity and abundance was studied. The abundance of adult insects and
      galled leaves were seven and 1.6 times higher in trees with a greater
      height/width of canopy (RHW) ratio, respectively. Gall parasitoid richness was
      1.8 times greater on trees with higher RHW. Zelus armillatus (Lepeletier &
      Serville) (Hemiptera: Reduviidae) and ant numbers were 5.8 and 2.7 higher on
      trees with the largest and smallest RHW, respectively. More complex plant
      architectures favored species diversity for galling insects and their natural
      enemies. The competition among four galling insect species for space and feeding
      and the evidence of "prudence strategy" were, for the first time, observed for
      galling insects in the Brazilian Cerrado biome.

PMID- 29192235
TI  - Multiplex single-cell visualization of nucleic acids and protein during HIV
      infection.
AB  - Technical limitations in simultaneous microscopic visualization of RNA, DNA, and
      proteins of HIV have curtailed progress in this field. To address this need we
      develop a microscopy approach, multiplex immunofluorescent cell-based detection
      of DNA, RNA and Protein (MICDDRP), which is based on branched DNA in situ
      hybridization technology. MICDDRP enables simultaneous single-cell visualization
      of HIV (a) spliced and unspliced RNA, (b) cytoplasmic and nuclear DNA, and (c)
      Gag. We use MICDDRP to visualize incoming capsid cores containing RNA and/or
      nascent DNA and follow reverse transcription kinetics. We also report
      transcriptional "bursts" of nascent RNA from integrated proviral DNA, and
      concomitant HIV-1, HIV-2 transcription in co-infected cells. MICDDRP can be used
      to simultaneously detect multiple viral nucleic acid intermediates, characterize
      the effects of host factors or drugs on steps of the HIV life cycle, or its
      reactivation from the latent state, thus facilitating the development of
      antivirals and latency reactivating agents.

PMID- 29192236
TI  - Estrogen attenuates AGTR1 expression to reduce pancreatic beta-cell death from
      high glucose.
AB  - Chronic exposure of pancreatic beta-cells to high glucose levels results in beta
      cell dysfunction and death. These effects can be protected by estrogen. The local
      pancreatic renin-angiotensin system (RAS) has been shown as a novel pathological
      pathway of high-glucose-induced cell death. The effect of estrogen on pancreatic
      RAS is still unknown. This study examines whether estrogen protects against
      pancreatic beta-cell death caused by glucotoxicity via a decrease in the
      pancreatic beta-cell RAS pathway. When INS-1 cells were cultured in a high
      glucose medium, cell death was significantly higher than when the cells were
      cultured in a basal glucose medium; similarly, there were also higher levels of
      AGTR1 and p47 ph  degrees  x mRNA, and protein expression. Moreover, the addition
      of 10-8 M 17beta-estradiol to INS-1 cells cultured in a high glucose medium
      markedly reduced cell death, AGTR1 and p47 ph  degrees  x mRNA levels, and
      protein expression. Similar results were demonstrated in the pancreatic islets.
      The presence of 10-8 M 17beta-estradiol, losartan, or a combination of both, in a
      high glucose medium had similar levels of reduction of p47 ph  degrees  x mRNA
      and protein expression, compared with those cultured in high glucose. Taken
      together, estrogen protected pancreatic beta-cells from high-glucose-induced cell
      death by reducing the AGTR1 pathway.

PMID- 29192239
TI  - A commentary on band-like calcification with simplified gyration and
      polymicrogyria: report of 10 new families and identification of five novel OCLN
      mutations.

PMID- 29192238
TI  - Evaluation of reported pathogenic variants and their frequencies in a Japanese
      population based on a whole-genome reference panel of 2049 individuals.
AB  - Clarifying allele frequencies of disease-related genetic variants in a population
      is important in genomic medicine; however, such data is not yet available for the
      Japanese population. To estimate frequencies of actionable pathogenic variants in
      the Japanese population, we examined the reported pathological variants in genes
      recommended by the American College of Medical Genetics and Genomics (ACMG) in
      our reference panel of genomic variations, 2KJPN, which was created by whole
      genome sequencing of 2049 individuals of the resident cohort of the Tohoku
      Medical Megabank Project. We searched for pathogenic variants in 2KJPN for 57
      autosomal ACMG-recommended genes responsible for 26 diseases and then examined
      their frequencies. By referring to public databases of pathogenic variations, we
      identified 143 reported pathogenic variants in 2KJPN for the 57 ACMG recommended
      genes based on a classification system. At the individual level, 21% of the
      individuals were found to have at least one reported pathogenic allele. We then
      conducted a literature survey to review the variants and to check for evidence of
      pathogenicity. Our results suggest that a substantial number of people have
      reported pathogenic alleles for the ACMG genes, and reviewing variants is
      indispensable for constructing the information infrastructure of genomic medicine
      for the Japanese population.

PMID- 29192240
TI  - Characterization of the B-cell receptor repertoires in peanut allergic subjects
      undergoing oral immunotherapy.
AB  - B-cell receptors (BCRs) play a critical role in adaptive immunity as they
      generate highly diverse immunoglobulin repertoires to recognize a wide variety of
      antigens. To better understand immune responses, it is critically important to
      establish a quantitative and rapid method to analyze BCR repertoire
      comprehensively. Here, we developed "Bcrip", a novel approach to characterize BCR
      repertoire by sequencing millions of BCR cDNA using next-generation sequencer.
      Using this method and quantitative real-time PCR, we analyzed expression levels
      and repertoires of BCRs in a total of 17 peanut allergic subjects' peripheral
      blood samples before and after receiving oral immunotherapy (OIT) or placebo. By
      our methods, we successfully identified all of variable (V), joining (J), and
      constant (C) regions, in an average of 79.1% of total reads and 99.6% of these
      VJC-mapped reads contained the C region corresponding to the isotypes that we
      aimed to analyze. In the 17 peanut allergic subjects' peripheral blood samples,
      we observed an oligoclonal enrichment of certain immunoglobulin heavy chain alpha
      (IGHA) and IGH gamma (IGHG) clones (P = 0.034 and P = 0.027, respectively) in
      peanut allergic subjects after OIT. This newly developed BCR sequencing and
      analysis method can be applied to investigate B-cell repertoires in various
      research areas, including food allergies as well as autoimmune and infectious
      diseases.

PMID- 29192241
TI  - MicroRNA-21 regulates Osteogenic Differentiation of Periodontal Ligament Stem
      Cells by targeting Smad5.
AB  - Human periodontal ligament stem cells (hPDLSCs) are mesenchymal stem cells (MSCs)
      derived from dental and craniofacial tissues that exhibit high potential for
      differentiation into osteoblasts. Recently, microRNAs (miRNAs) have been
      established to play important roles in MSC osteogenesis. In the current study, we
      report that miR-21 was down-regulated in osteogenically differentiated PDLSCs.
      Overexpression of miR-21 significantly inhibited osteogenesis of hPDLSC, whereas
      its inhibition demonstrated the opposite effects. Furthermore, SMAD family member
      5 (Smad5) was predicted to be a downstream target of miR-21 and was shown to
      undergo up-regulation in PDLSCs induced toward osteogenesis. Moreover, Smad5 and
      Runx2, which are the critical transcription factors in osteogenic
      differentiation, were predicted to be targets of miR-21. Suppression of miR-21
      expression increased the level of Smad5 in vitro and during in vivo
      transplantation experiments. Furthermore, suppression of Smad5 inhibited
      osteogenic differentiation and decreased the protein level of Runx2. Taken
      together, these results suggested that miR-21 be mechanistically implicated in
      the regulation of osteogenic differentiation of hPDLSCs by targeting Smad5.

PMID- 29192237
TI  - Stem cells and genome editing: approaches to tissue regeneration and regenerative
      medicine.
AB  - Understanding the basis of regeneration of each tissue and organ, and
      incorporating this knowledge into clinical treatments for degenerative tissues
      and organs in patients, are major goals for researchers in regenerative biology.
      Here we provide an overview of current work, from high-regeneration animal
      models, to stem cell-based culture models, transplantation technologies, large
      animal chimeric models, and programmable nuclease-based genome-editing
      technologies. Three-dimensional culture generating organoids, which represents
      intact tissue/organ identity including cell fate and morphology are getting more
      general approaches in the fields by taking advantage of embryonic stem cells,
      induced pluripotent stem cells and adult stem cells. The organoid culture system
      potentially has profound impact on the field of regenerative medicine. We also
      emphasize that the large animal model, in particular pig model would be a hope to
      manufacture humanized organs in in vivo empty (vacant) niche, which now
      potentially allows not only appropriate cell fate identity but nearly the same
      property as human organs in size. Therefore, integrative and collaborative
      researches across different fields might be critical to the aims needed in
      clinical trial.

PMID- 29192242
TI  - Impact-related microspherules in Late Pleistocene Alaskan and Yukon "muck"
      deposits signify recurrent episodes of catastrophic emplacement.
AB  - Large quantities of impact-related microspherules have been found in fine-grained
      sediments retained within seven out of nine, radiocarbon-dated, Late Pleistocene
      mammoth (Mammuthus primigenius) and bison (Bison priscus) skull fragments. The
      well-preserved fossils were recovered from frozen "muck" deposits (organic-rich
      silt) exposed within the Fairbanks and Klondike mining districts of Alaska, USA,
      and the Yukon Territory, Canada. In addition, elevated platinum abundances were
      found in sediment analysed from three out of four fossil skulls. In view of this
      new evidence, the mucks and their well-preserved but highly disrupted and damaged
      vertebrate and botanical remains are reinterpreted in part as blast deposits that
      resulted from several episodes of airbursts and ground/ice impacts within the
      northern hemisphere during Late Pleistocene time (~46-11 ka B.P.). Such a
      scenario might be explained by encounters with cometary debris in Earth-crossing
      orbits (Taurid Complex) that was generated by fragmentation of a large short
      period comet within the inner Solar System.

PMID- 29192243
TI  - Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells.
AB  - Although runt-related transcription factor 1 (RUNX1) and its associating core
      binding factor-beta (CBFB) play pivotal roles in leukemogenesis, and inhibition
      of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic
      therapies, it has been elusive how leukemic cells could acquire the serious
      resistance against RUNX1-inhibition therapies and also whether CBFB could
      participate in this process. Here, we show evidence that p53 (TP53) and CBFB are
      sequentially up-regulated in response to RUNX1 depletion, and their mutual
      interaction causes the physiological resistance against chemotherapy for acute
      myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene
      silencing directly binds to CBFB promoter and stimulates its transcription as
      well as its translation, which in turn acts as a platform for the stabilization
      of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed,
      AML cells derived from relapsed cases exhibited higher CBFB expression levels
      compared to those from primary AML cells at diagnosis, and these CBFB expressions
      were positively correlated to those of p53. Our present results underscore the
      importance of RUNX1-p53-CBFB regulatory loop in the development and/or
      maintenance of AML cells, which could be targeted at any sides of this triangle
      in strategizing anti-leukemia therapies.

PMID- 29192244
TI  - Adsorbed Conformations of PCE Superplasticizers in Cement Pore Solution Unraveled
      by Molecular Dynamics Simulations.
AB  - The conformations of polycarboxylate ether (PCE) type superplasticizer polymers
      adsorbed on the surface of MgO in cement pore solution are simulated by molecular
      dynamics (MD). Three types of PCEs commonly applied to concrete are simulated,
      namely a methacrylate type PCE (PCEM-P), an allyl ether type PCE (PCEA-P), and an
      isoprenyl ether type PCE (PCEI-P) with ethylene oxide (EO) unit numbers (P) of
      25, 34 and 25, respectively. It is observed that the adsorbed layer thickness is
      inversely proportional to the experimentally measured adsorbed amount at the
      initial paste flow of 26 +/- 0.5 cm. Simulation results indicate that the
      adsorbed layer thickness is sensitive to the initial polymer orientations against
      the model MgO surface. I.e., polymer molecules initially placed
      parallel/perpendicularly against the MgO surface gradually forms a train shaped
      or a loop and tail adsorption profile, respectively. As a result, the loop and
      tail shaped conformation gives a higher layer thickness.

PMID- 29192245
TI  - Obesity: Ankyrin-B in susceptibility to obesity.

PMID- 29192247
TI  - Immunotherapy: PDL1 restoration reverses T1DM.

PMID- 29192248
TI  - Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis.
AB  - Liver plays a crucial role in controlling energy homeostasis in mammals, although
      the exact mechanism by which it influences other peripheral tissues has yet to be
      addressed. Here we show that Creb regulates transcriptional co-activator (Crtc) 2
      is a major regulator of whole-body energy metabolism. Crtc2 liver-specific
      knockout lowers blood glucose levels with improved glucose and insulin tolerance.
      Liver-specific knockout mice display increased energy expenditure with smaller
      lipid droplets in adipose depots. Both plasma and hepatic Fgf21 levels are
      increased in Crtc2 liver-specific knockout mice, as a result of the reduced miR
      34a expression regulated by Creb/Crtc2 and the induction of Sirt1 and Pparalpha.
      Ectopic expression of miR-34a reverses the metabolic changes in knockout liver.
      We suggest that Creb/Crtc2 negatively regulates the Sirt1/Pparalpha/Fgf21 axis
      via the induction of miR-34a under diet-induced obesity and insulin-resistant
      conditions.

PMID- 29192249
TI  - Multilocus DNA barcoding - Species Identification with Multilocus Data.
AB  - Species identification using DNA sequences, known as DNA barcoding has been
      widely used in many applied fields. Current barcoding methods are usually based
      on a single mitochondrial locus, such as cytochrome c oxidase subunit I (COI).
      This type of barcoding method does not always work when applied to species
      separated by short divergence times or that contain introgressed genes from
      closely related species. Herein we introduce a more effective multi-locus
      barcoding framework that is based on gene capture and "next-generation"
      sequencing. We selected 500 independent nuclear markers for ray-finned fishes and
      designed a three-step pipeline for multilocus DNA barcoding. We applied our
      method on two exemplar datasets each containing a pair of sister fish species:
      Siniperca chuatsi vs. Sini. kneri and Sicydium altum vs. Sicy. adelum, where the
      COI barcoding approach failed. Both of our empirical and simulated results
      demonstrated that under limited gene flow and enough separation time, we could
      correctly identify species using multilocus barcoding method. We anticipate that,
      as the cost of DNA sequencing continues to fall that our multilocus barcoding
      approach will eclipse existing single-locus DNA barcoding methods as a means to
      better understand the diversity of the living world.

PMID- 29192250
TI  - Coupling optogenetics and light-sheet microscopy, a method to study Wnt signaling
      during embryogenesis.
AB  - Optogenetics allows precise, fast and reversible intervention in biological
      processes. Light-sheet microscopy allows observation of the full course of
      Drosophila embryonic development from egg to larva. Bringing the two approaches
      together allows unparalleled precision into the temporal regulation of signaling
      pathways and cellular processes in vivo. To develop this method, we investigated
      the regulation of canonical Wnt signaling during anterior-posterior patterning of
      the Drosophila embryonic epidermis. Cryptochrome 2 (CRY2) from Arabidopsis
      Thaliana was fused to mCherry fluorescent protein and Drosophila beta-catenin to
      form an easy to visualize optogenetic switch. Blue light illumination caused
      oligomerization of the fusion protein and inhibited downstream Wnt signaling in
      vitro and in vivo. Temporal inactivation of beta-catenin confirmed that Wnt
      signaling is required not only for Drosophila pattern formation, but also for
      maintenance later in development. We anticipate that this method will be easily
      extendable to other developmental signaling pathways and many other experimental
      systems.

PMID- 29192251
TI  - Access to a main alphaherpesvirus receptor, located basolaterally in the
      respiratory epithelium, is masked by intercellular junctions.
AB  - The respiratory epithelium of humans and animals is frequently exposed to
      alphaherpesviruses, originating from either external exposure or reactivation
      from latency. To date, the polarity of alphaherpesvirus infection in the
      respiratory epithelium and the role of respiratory epithelial integrity herein
      has not been studied. Equine herpesvirus type 1 (EHV1), a well-known member of
      the alphaherpesvirus family, was used to infect equine respiratory mucosal
      explants and primary equine respiratory epithelial cells (EREC), grown at the air
      liquid interface. EHV1 binding to and infection of mucosal explants was greatly
      enhanced upon destruction of the respiratory epithelium integrity with EGTA or N
      acetylcysteine. EHV1 preferentially bound to and entered EREC at basolateral cell
      surfaces. Restriction of infection via apical inoculation was overcome by
      disruption of intercellular junctions. Finally, basolateral but not apical EHV1
      infection of EREC was dependent on cellular N-linked glycans. Overall, our
      findings demonstrate that integrity of the respiratory epithelium is crucial in
      the host's innate defence against primary alphaherpesvirus infections. In
      addition, by targeting a basolaterally located receptor in the respiratory
      epithelium, alphaherpesviruses have generated a strategy to efficiently escape
      from host defence mechanisms during reactivation from latency.

PMID- 29192253
TI  - Chitosan-Graphene Oxide 3D scaffolds as Promising Tools for Bone Regeneration in
      Critical-Size Mouse Calvarial Defects.
AB  - Limited self-regenerating capacity of human skeleton makes the reconstruction of
      critical size bone defect a significant challenge for clinical practice. Aimed
      for regenerating bone tissues, this study was designed to investigate osteogenic
      differentiation, along with bone repair capacity of 3D chitosan (CHT) scaffolds
      enriched with graphene oxide (GO) in critical-sized mouse calvarial defect.
      Histopathological/histomorphometry and scanning electron microscopy(SEM) analysis
      of the implants revealed larger amount of new bone in the CHT/GO-filled defects
      compared with CHT alone (p < 0.001). When combined with GO, CHT scaffolds
      synergistically promoted the increase of alkaline phosphatase activity both in
      vitro and in vivo experiments. This enhanced osteogenesis was corroborated with
      increased expression of bone morphogenetic protein (BMP) and Runx-2 up to week 4
      post-implantation, which showed that GO facilitates the differentiation of
      osteoprogenitor cells. Meanwhile, osteogenesis was promoted by GO at the late
      stage as well, as indicated by the up-regulation of osteopontin and osteocalcin
      at week 8 and overexpressed at week 18, for both markers. Our data suggest that
      CHT/GO biomaterial could represent a promising tool for the reconstruction of
      large bone defects, without using exogenous living cells or growth factors.

PMID- 29192252
TI  - Restoration of patterned vision with an engineered photoactivatable G protein
      coupled receptor.
AB  - Retinitis pigmentosa results in blindness due to degeneration of photoreceptors,
      but spares other retinal cells, leading to the hope that expression of light
      activated signaling proteins in the surviving cells could restore vision. We used
      a retinal G protein-coupled receptor, mGluR2, which we chemically engineered to
      respond to light. In retinal ganglion cells (RGCs) of blind rd1 mice, photoswitch
      charged mGluR2 ("SNAG-mGluR2") evoked robust OFF responses to light, but not in
      wild-type retinas, revealing selectivity for RGCs that have lost photoreceptor
      input. SNAG-mGluR2 enabled animals to discriminate parallel from perpendicular
      lines and parallel lines at varying spacing. Simultaneous viral delivery of the
      inhibitory SNAG-mGluR2 and excitatory light-activated ionotropic glutamate
      receptor LiGluR yielded a distribution of expression ratios, restoration of ON,
      OFF and ON-OFF light responses and improved visual acuity. Thus, SNAG-mGluR2
      restores patterned vision and combinatorial light response diversity provides a
      new logic for enhanced-acuity retinal prosthetics.

PMID- 29192254
TI  - Effect of Src Kinase inhibition on Cytochrome c, Smac/DIABLO and Apoptosis
      Inducing Factor (AIF) Following Cerebral Hypoxia-Ischemia in Newborn Piglets.
AB  - We have previously shown that cerebral Hypoxia-ischemia (HI) results in
      activation of Src kinase in the newborn piglet brain. We investigated the
      regulatory mechanism by which the pre-apoptotic proteins translocate from
      mitochondria to the cytosol during HI through the Src kinase. Newborn piglets
      were divided into 3 groups (n = 5/group): normoxic (Nx), HI and HI pre-treated
      with Src kinase inhibitor PP2 (PP2 + HI). Brain tissue HI was verified by
      neuropathological analysis and by Adenosine Triphosphate (ATP) and
      Phosphocreatine (PCr) levels. We used western blots, immunohistochemistry, H&E
      and biochemical enzyme assays to determine the role of Src kinase on
      mitochondrial membrane apoptotic protein trafficking. HI resulted in decreased
      ATP and PCr levels, neuropathological changes and increased levels of cytochrome
      c, Smac/DIABLO and AIF in the cytosol while their levels were decreased in
      mitochondria compared to Nx. PP2 decreased the cytosolic levels of pre-apoptotic
      proteins, attenuated the neuropathological changes and apoptosis and decreased
      the HI-induced increased activity of caspase-3. Our data suggest that Src kinase
      may represent a potential target that could interrupt the enzymatic activation of
      the caspase dependent cell death pathway.

PMID- 29192255
TI  - The mitochondrial genome of the wolfberry fruit fly, Neoceratitis asiatica
      (Becker) (Diptera: Tephritidae) and the phylogeny of Neoceratitis Hendel genus.
AB  - Neoceratitis asiatica (Becker) (Diptera: Tephritidae) is one of the most
      important fruit pestsof wolfberry which is a traditional Chinese medicinal herb.
      We characterized the complete mitochondrial genome of N. asiatica and described
      its organization in this study. This mitogenome had a total length of 15,481 bp,
      consisting of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non
      coding region (A + T-rich control region). The overall base composition of N.
      asiatica in descending order was 40.6% A, 8.5% G, 38.4% T and 12.6% C. The
      phylogenetic relationships shows that Ceratitis capitata and N. asiatica may be
      sister taxa. This is the first report of the complete mitochondrial genome of a
      member of the Neoceratitis Genus and the complete mitochondrial genome sequence
      may provide useful information for phylogenetic analysis and studies between the
      genera Ceratitis and Neoceratitis.

PMID- 29192256
TI  - Posterior parietal cortex evaluates visuoproprioceptive congruence based on brief
      visual information.
AB  - To represent one's upper limbs for action, the brain relies on a combined
      position estimate based on visual and proprioceptive information. Monkey
      neurophysiology and human brain imaging suggest that the underlying operations
      are implemented in a network of fronto-parietal and occipitotemporal cortical
      areas. Recently, a potential hierarchical arrangement of these areas has been
      proposed, emphasizing the posterior parietal cortex (PPC) in early multisensory
      comparison and integration. Here, we used functional magnetic resonance imaging
      (fMRI) and a virtual reality-based setup to briefly (0.5 s) present healthy human
      participants photorealistic virtual hands, of matching or nonmatching anatomical
      side, or objects at the same or a different location than their real hidden left
      or right hand. The inferior parietal lobe (IPL) of the left PPC showed a
      significant preference for congruent visuoproprioceptive hand position
      information. Moreover, the left body part-selective extrastriate body area (EBA;
      functionally localized) significantly increased its coupling with the left IPL
      during visuoproprioceptive congruence vs. incongruence. Our results suggest that
      the PPC implements early visuoproprioceptive comparison and integration
      processes, likely relying on information exchange with the EBA.

PMID- 29192257
TI  - Stroke: 'Brain health': what is it, what can we do about it and when should we
      start?

PMID- 29192258
TI  - Alzheimer disease: CRISPR activation reveals hidden gamma-secretase defect in
      fibroblasts from patients with familial AD.

PMID- 29192259
TI  - CNS infections: Zika virus mutation associated with increased infectivity,
      mortality and severe microcephaly.

PMID- 29192261
TI  - Parkinson disease: Blood transcriptomics for Parkinson disease?

PMID- 29192262
TI  - Parkinson disease: Lysosome storage disorder risk genes linked to PD.

PMID- 29192260
TI  - Antisense oligonucleotides: the next frontier for treatment of neurological
      disorders.
AB  - Antisense oligonucleotides (ASOs) were first discovered to influence RNA
      processing and modulate protein expression over two decades ago; however,
      progress translating these agents into the clinic has been hampered by inadequate
      target engagement, insufficient biological activity, and off-target toxic
      effects. Over the years, novel chemical modifications of ASOs have been employed
      to address these issues. These modifications, in combination with elucidation of
      the mechanism of action of ASOs and improved clinical trial design, have provided
      momentum for the translation of ASO-based strategies into therapies. Many
      neurological conditions lack an effective treatment; however, as research
      progressively disentangles the pathogenic mechanisms of these diseases, they
      provide an ideal platform to test ASO-based strategies. This steady progress
      reached a pinnacle in the past few years with approvals of ASOs for the treatment
      of spinal muscular atrophy and Duchenne muscular dystrophy, which represent
      landmarks in a field in which disease-modifying therapies were virtually non
      existent. With the rapid development of improved next-generation ASOs toward
      clinical application, this technology now holds the potential to have a dramatic
      effect on the treatment of many neurological conditions in the near future.

PMID- 29192263
TI  - Comprehensive high-throughput image analysis for therapeutic efficacy of
      architecturally complex heterotypic organoids.
AB  - Bioengineered three-dimensional (3D) tumor models that incorporate heterotypic
      cellular communication are gaining interest as they can recapitulate key features
      regarding the intrinsic heterogeneity of cancer tissues. However, the
      architectural complexity and heterogeneous contents associated with these models
      pose a challenge for toxicological assays to accurately report treatment
      outcomes. To address this issue, we describe a comprehensive image analysis
      procedure for structurally complex organotypic cultures (CALYPSO) applied to
      fluorescence-based assays to extract multiparametric readouts of treatment
      effects for heterotypic tumor cultures that enables advanced analyses. The
      capacity of this approach is exemplified on various 3D models including
      adherent/suspension, mono-/heterocellular cultures and several disease types. The
      subsequent analysis revealed specific morphological effects of oxaliplatin
      chemotherapy, radiotherapy, and photodynamic therapy. The procedure can be
      readily implemented in most laboratories to facilitate high-throughput
      toxicological screening of pharmaceutical agents and treatment regimens on
      organotypic cultures of human disease to expedite drug and therapy development.

PMID- 29192266
TI  - ACNP 56th Annual Meeting: Poster Session III, December 6, 2017.

PMID- 29192265
TI  - ACNP 56th Annual Meeting: Poster Session I, December 4, 2017.

PMID- 29192267
TI  - ACNP 56th Annual Meeting: Poster Session II, December 5, 2017.

PMID- 29192268
TI  - ACNP 56th Annual Meeting: Keyword Index.

PMID- 29192269
TI  - ACNP 56th Annual Meeting: Panels, Mini-Panels and Study Groups, December 4 - 7,
      2017.

PMID- 29192270
TI  - HIDEEP: a systems approach to predict hormone impacts on drug efficacy based on
      effect paths.
AB  - Experimental evidence has shown that some of the human endogenous hormones
      significantly affect drug efficacy. Since hormone status varies with individual
      physiological states, it is essential to understand the interplay of hormones and
      drugs for precision medicine. Here, we developed an in silico method to predict
      interactions between 283 human endogenous hormones and 590 drugs for 20 diseases
      including cancers and non-cancer diseases. We extracted hormone effect paths and
      drug effect paths from a large-scale molecular network that contains protein
      interactions, transcriptional regulations, and signaling interactions. If two
      kinds of effect paths for a hormone-drug pair intersect closely, we expect that
      the influence of the hormone on the drug efficacy is significant. It has been
      shown that the proposed method correctly distinguishes hormone-drug pairs with
      known interactions from random pairs in blind experiments. In addition, the
      method can suggest underlying interaction mechanisms at the molecular level so
      that it helps us to better understand the interplay of hormones and drugs.

PMID- 29192271
TI  - Tailoring magnetic properties of multicomponent layered structure via current
      annealing in FePd thin films.
AB  - Multicomponent layered systems with tailored magnetic properties were fabricated
      via current annealing from homogeneous Fe67Pd33 thin films, deposited via radio
      frequency sputtering on Si/SiO2 substrates from composite target. To promote
      spontaneous nano-structuring and phase separation, selected samples were
      subjected to current annealing in vacuum, with a controlled oxygen pressure,
      using various current densities for a fixed time and, as a consequence, different
      phases and microstructures were obtained. In particular, the formation of
      magnetite in different amount was observed beside other iron oxides and metallic
      phases. Microstructures and magnetic properties evolution as a function of
      annealing current were studied and interpreted with different techniques.
      Moreover, the temperature profile across the film thickness was modelled and its
      role in the selective oxidation of iron was analysed. Results show that is
      possible to topologically control the phases formation across the film thickness
      and simultaneously tailor the magnetic properties of the system.

PMID- 29192273
TI  - Publisher Correction: Ellipticity dependence of high-harmonic generation in
      solids originating from coupled intraband and interband dynamics.
AB  - The published version of this Article contained an error in the second sentence
      of the fourth paragraph of the subheaded section "Ellipticity and helicity of the
      emitted harmonics". The final exponent in this sentence should read: inpi/2. This
      has now been corrected in the PDF and HTML versions of the Article.

PMID- 29192272
TI  - Ribosomal stress and Tp53-mediated neuronal apoptosis in response to capsid
      protein of the Zika virus.
AB  - We report here that in rat and human neuroprogenitor cells as well as rat
      embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress
      that is characterized by structural disruption of the nucleolus. The anti
      nucleolar effects were most pronounced in postmitotic neurons. Moreover, in the
      latter system, nucleolar presence of ZIKV capsid protein (ZIKV-C) was associated
      with ribosomal stress and apoptosis. Deletion of 22 C-terminal residues of ZIKV-C
      prevented nucleolar localization, ribosomal stress and apoptosis. Consistent with
      a casual relationship between ZIKV-C-induced ribosomal stress and apoptosis, ZIKV
      C-overexpressing neurons were protected by loss-of-function manipulations
      targeting the ribosomal stress effector Tp53 or knockdown of the ribosomal stress
      mediator RPL11. Finally, capsid protein of Dengue virus, but not West Nile virus,
      induced ribosomal stress and apoptosis. Thus, anti-nucleolar and pro-apoptotic
      effects of protein C are flavivirus-species specific. In the case of ZIKV, capsid
      protein-mediated ribosomal stress may contribute to neuronal death,
      neurodevelopmental disruption and microcephaly.

PMID- 29192274
TI  - Synthesis of structurally controlled hyperbranched polymers using a monomer
      having hierarchical reactivity.
AB  - Hyperbranched polymers (HBPs) have attracted significant attention because of
      their characteristic topological structure associated with their unique physical
      properties compared with those of the corresponding linear polymers. Dendrimers
      are the most structurally controlled HBPs, but the necessity of a stepwise
      synthesis significantly limits their applications in materials science. Several
      methods have been developed to synthesize HBPs by a one-step procedure, as
      exemplified by the use of AB2 monomers and AB' inimers under condensation and
      self-condensing vinyl polymerization conditions. However, none of these methods
      provides structurally controlled HBPs over the three-dimensional (3D) structure,
      i.e., molecular weight, dispersity, number of branching points, branching
      density, and chain-end functionalities, except under special conditions. Here, we
      introduce a monomer design concept involving two functional groups with
      hierarchical reactivity and demonstrate the controlled synthesis of dendritic
      HBPs over the 3D structure by the copolymerization of the designed monomer and
      acrylates under living radical polymerization conditions.

PMID- 29192275
TI  - The habitability of the Milky Way during the active phase of its central
      supermassive black hole.
AB  - During the peak of their accretion phase, supermassive black holes in galactic
      cores are known to emit very high levels of ionizing radiation, becoming visible
      over intergalactic distances as quasars or active galactic nuclei (AGN). Here, we
      quantify the extent to which the activity of the supermassive black hole at the
      center of the Milky Way, known as Sagittarius A* (Sgr A*), may have affected the
      habitability of Earth-like planets in our Galaxy. We focus on the amount of
      atmospheric loss and on the possible biological damage suffered by planets
      exposed to X-ray and extreme ultraviolet (XUV) radiation produced during the peak
      of the active phase of Sgr A*. We find that terrestrial planets could lose a
      total atmospheric mass comparable to that of present day Earth even at large
      distances (~1 kiloparsec) from the galactic center. Furthermore, we find that the
      direct biological damage caused by Sgr A* to surface life on planets not properly
      screened by an atmosphere was probably significant during the AGN phase, possibly
      hindering the development of complex life within a few kiloparsecs from the
      galactic center.

PMID- 29192276
TI  - Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage.
AB  - Upon induction of DNA breaks, ATM activation leads to a cascade of local
      chromatin modifications that promote efficient recruitment of DNA repair
      proteins. Errors in this DNA repair pathway lead to genomic instability and
      cancer predisposition. Here, we show that the protein lysine methyltransferase
      G9a (also known as EHMT2) and GLP1 (also known as EHMT1) are critical components
      of the DNA repair pathway. G9a and GLP1 rapidly localizes to DNA breaks, with
      GLP1 localization being dependent on G9a. ATM phosphorylation of G9a on serine
      569 is required for its recruitment to DNA breaks. G9a catalytic activity is
      required for the early recruitment of DNA repair factors including 53BP and BRCA1
      to DNA breaks. Inhibition of G9a catalytic activity disrupts DNA repair pathways
      and increases sensitivity to ionizing radiation. Thus, G9a is a potential
      therapeutic target in the DNA repair pathway.

PMID- 29192277
TI  - Graphene-edge dielectrophoretic tweezers for trapping of biomolecules.
AB  - The many unique properties of graphene, such as the tunable optical, electrical,
      and plasmonic response make it ideally suited for applications such as
      biosensing. As with other surface-based biosensors, however, the performance is
      limited by the diffusive transport of target molecules to the surface. Here we
      show that atomically sharp edges of monolayer graphene can generate singular
      electrical field gradients for trapping biomolecules via dielectrophoresis.
      Graphene-edge dielectrophoresis pushes the physical limit of gradient-force-based
      trapping by creating atomically sharp tweezers. We have fabricated locally
      backgated devices with an 8-nm-thick HfO2 dielectric layer and chemical-vapor
      deposited graphene to generate 10* higher gradient forces as compared to metal
      electrodes. We further demonstrate near-100% position-controlled particle
      trapping at voltages as low as 0.45 V with nanodiamonds, nanobeads, and DNA from
      bulk solution within seconds. This trapping scheme can be seamlessly integrated
      with sensors utilizing graphene as well as other two-dimensional materials.

PMID- 29192278
TI  - Profiling of different pancreatic cancer cells used as models for metastatic
      behaviour shows large variation in their N-glycosylation.
AB  - To characterise pancreatic cancer cells from different sources which are used as
      model systems to study the metastatic behaviour in pancreatic ductal
      adenocarcinoma (PDAC), we compared the N-glycan imprint of four PDAC cells which
      were previously shown to differ in their galectin-4 expression and metastatic
      potential in vivo. Next to the sister cell lines Pa-Tu-8988S and Pa-Tu-8988T,
      which were isolated from the same liver metastasis of a PDAC, this included two
      primary PDAC cell cultures, PDAC1 and PDAC2. Additionally, we extended the N
      glycan profiling to a normal, immortalized pancreatic duct cell line. Our results
      revealed major differences in the N-glycosylation of the different PDAC cells as
      well as compared to the control cell line, suggesting changes of the N
      glycosylation in PDAC. The N-glycan profiles of the PDAC cells, however, differed
      vastly as well and demonstrate the diversity of PDAC model systems, which
      ultimately affects the interpretation of functional studies. The results from
      this study form the basis for further biological evaluation of the role of
      protein glycosylation in PDAC and highlight that conclusions from one cell line
      cannot be generalised, but should be regarded in the context of the corresponding
      phenotype.

PMID- 29192279
TI  - Self-righting potential and the evolution of shell shape in Galapagos tortoises.
AB  - Self-righting, the capacity of an animal to self-turn after falling on its back,
      is a fitness-related trait. Delayed self-righting can result in loss of mating
      opportunities or death. Traits involved in self-righting may therefore be under
      selection. Galapagos giant tortoises have two main shell morphologies -
      saddleback and domed - that have been proposed to be adaptive. The more sloped
      shape on the sides of the shell and the longer extension of neck and legs of the
      saddlebacks could have evolved to optimize self-righting. The drier environments
      with more uneven surfaces where the saddleback tortoises occur increases their
      risk to fall on their back while walking. The ability to fast overturn could
      reduce the danger of dying. To test this hypothesis, we used 3D shell
      reconstructions of 89 Galapagos giant tortoises from three domed and two
      saddleback species to compare self-righting potential of the two shell
      morphotypes. Our results indicate that saddleback shells require higher energy
      input to self-right than domed ones. This suggests that several traits associated
      with the saddleback shell morphology could have evolved to facilitate self
      righting. Studying the functional performances of fitness-related traits, as in
      this work, could provide important insight into the adaptive value of traits.

PMID- 29192280
TI  - Improved Detection of Cytokines Produced by Invariant NKT Cells.
AB  - Invariant Natural killer T (iNKT) cells rapidly produce copious amounts of
      multiple cytokines after in vivo activation, allowing for the direct detection of
      a number of cytokines directly ex vivo. However, for some cytokines this approach
      is suboptimal. Here, we report technical variations that allow the improved
      detection of IL-4, IL-10, IL-13 and IL-17A ex vivo. Furthermore, we describe an
      alternative approach for stimulation of iNKT cells in vitro that allows a
      significantly improved detection of cytokines produced by iNKT cells. Together,
      these protocols allow the detection of iNKT cell cytokines ex vivo and in vitro
      with increased sensitivity.

PMID- 29192281
TI  - High-speed, high-frequency ultrasound, in utero vector-flow imaging of mouse
      embryos.
AB  - Real-time imaging of the embryonic murine cardiovascular system is challenging
      due to the small size of the mouse embryo and rapid heart rate. High-frequency,
      linear-array ultrasound systems designed for small-animal imaging provide high
      frame-rate and Doppler modes but are limited in regards to the field of view that
      can be imaged at fine-temporal and -spatial resolution. Here, a plane-wave
      imaging method was used to obtain high-speed image data from in utero mouse
      embryos and multi-angle, vector-flow algorithms were applied to the data to
      provide information on blood flow patterns in major organs. An 18-MHz linear
      array was used to acquire plane-wave data at absolute frame rates >=10 kHz using
      a set of fixed transmission angles. After beamforming, vector-flow processing and
      image compounding, effective frame rates were on the order of 2 kHz. Data were
      acquired from the embryonic liver, heart and umbilical cord. Vector-flow results
      clearly revealed the complex nature of blood-flow patterns in the embryo with
      fine-temporal and -spatial resolution.

PMID- 29192282
TI  - Functionalized gold nanorod nanocomposite system to modulate differentiation of
      human mesenchymal stem cells into neural-like progenitors.
AB  - A 2D multifunctional nanocomposite system of gold nanorods (AuNRs) was developed.
      Gold nanorods were functionalized via polyethylene glycol with a terminal amine,
      and, were characterized using transmission and scanning electron microscopy,
      ultra violet-visible and X-ray photoelectron spectroscopy, and Zeta-potential.
      The system was cytocompatible to and maintained the integrity of Schwann cells.
      The neurogenic potential of adipose tissue - derived human mesenchymal stem cells
      (hMSCs) was evaluated in vitro. The expression pattern and localization of
      Vimentin confirmed the mesenchymal origin of cells and tracked morphological
      changes during differentiation. The expression patterns of S100beta and glial
      fibrillary acidic protein (GFAP), were used as indicator for neural
      differentiation. Results suggested that this process was enhanced when the cells
      were seeded on the AuNRs compared to the tissue-culture surface. The present
      study indicates that the design and the surface properties of the AuNRs enhances
      neural differentiation of hMSCs and hence, would be beneficial for neural tissue
      engineering scaffolds.

PMID- 29192283
TI  - Chemical Changes in Layered Ferroelectric Semiconductors Induced by Helium Ion
      Beam.
AB  - Multi-material systems interfaced with 2D materials, or entirely new 3D
      heterostructures can lead to the next generation multi-functional device
      architectures. Physical and chemical control at the nanoscale is also necessary
      tailor these materials as functional structures approach physical limit. 2D
      transition metal thiophosphates (TPS), with a general formulae Cu1-xIn1+x/3P2S6,
      have shown ferroelectric polarization behavior with a T c above the room
      temperature, making them attractive candidates for designing both: chemical and
      physical properties. Our previous studies have demonstrated that ferroic order
      persists on the surface, and that spinoidal decomposition of ferroelectric and
      paraelectric phases occurs in non-stoichiometric Cu/In ratio formulations. Here,
      we discuss the chemical changes induced by helium ion irradiation. We explore the
      TPS compound library with varying Cu/In ratio, using Helium Ion Microscopy,
      Atomic Force Microscopy (AFM), and Time of Flight-Secondary Ion Mass Spectrometry
      (ToF-SIMS). We correlate physical nano- and micro- structures to the helium ion
      dose, as well as chemical signatures of copper, oxygen and sulfur. Our ToF-SIMS
      results show that He ion irradiation leads to oxygen penetration into the
      irradiated areas, and diffuses along the Cu-rich domains to the extent of the
      stopping distance of the helium ions.

PMID- 29192284
TI  - Seasonality and brain size are negatively associated in frogs: evidence for the
      expensive brain framework.
AB  - The challenges of seasonal environments are thought to contribute to brain
      evolution, but in which way is debated. According to the Cognitive Buffer
      Hypothesis (CBH) brain size should increase with seasonality, as the cognitive
      benefits of a larger brain should help overcoming periods of food scarcity via,
      for instance, increased behavioral flexibility. However, in line with the
      Expensive Brain Framework (EBF) brain size should decrease with seasonality
      because a smaller brain confers energetic benefits in periods of food scarcity.
      Empirical evidence is inconclusive and mostly limited to homoeothermic animals.
      Here we used phylogenetic comparative analyses to test the impact of seasonality
      on brain evolution across 30 species of anurans (frogs) experiencing a wide range
      of temperature and precipitation. Our results support the EBF because relative
      brain size and the size of the optic tectum were negatively correlated with
      variability in temperature. In contrast, we found no association between the
      variability in precipitation and the length of the dry season with either brain
      size or the sizes of other major brain regions. We suggest that seasonality
      induced food scarcity resulting from higher variability in temperature constrains
      brain size evolution in anurans. Less seasonal environments may therefore
      facilitate the evolution of larger brains in poikilothermic animals.

PMID- 29192285
TI  - Deal watch: Roche taps potential antibiotics mine with Warp Drive Bio.

PMID- 29192286
TI  - Mechanistic enzymology in drug discovery: a fresh perspective.
AB  - Given the therapeutic and commercial success of small-molecule enzyme inhibitors,
      as exemplified by kinase inhibitors in oncology, a major focus of current drug
      discovery and development efforts is on enzyme targets. Understanding the course
      of an enzyme-catalysed reaction can help to conceptualize different types of
      inhibitor and to inform the design of screens to identify desired mechanisms.
      Exploiting this information allows the thorough evaluation of diverse compounds,
      providing the knowledge required to efficiently optimize leads towards
      differentiated candidate drugs. This review highlights the rationale for
      conducting high-quality mechanistic enzymology studies and considers the added
      value in combining such studies with orthogonal biophysical methods.

PMID- 29192288
TI  - Optical charge state control of spin defects in 4H-SiC.
AB  - Defects in silicon carbide (SiC) have emerged as a favorable platform for
      optically active spin-based quantum technologies. Spin qubits exist in specific
      charge states of these defects, where the ability to control these states can
      provide enhanced spin-dependent readout and long-term charge stability. We
      investigate this charge state control for two major spin qubits in 4H-SiC, the
      divacancy and silicon vacancy, obtaining bidirectional optical charge conversion
      between the bright and dark states of these defects. We measure increased
      photoluminescence from divacancy ensembles by up to three orders of magnitude
      using near-ultraviolet excitation, depending on the substrate, and without
      degrading the electron spin coherence time. This charge conversion remains stable
      for hours at cryogenic temperatures, allowing spatial and persistent patterning
      of the charge state populations. We develop a comprehensive model of the defects
      and optical processes involved, offering a strong basis to improve material
      design and to develop quantum applications in SiC.

PMID- 29192289
TI  - Caspase-3/-7-Specific Metabolic Precursor for Bioorthogonal Tracking of Tumor
      Apoptosis.
AB  - Apoptosis is one of the most important intracellular events in living cell, which
      is a programmed cell death interrelated with caspase enzyme activity for
      maintaining homeostasis in multicellular organisms. Therefore, direct apoptosis
      imaging of living cells can provide enormous advantages for diagnosis, drug
      discovery, and therapeutic monitoring in various diseases. However, a method of
      direct apoptosis imaging has not been fully validated, especially for live cells
      in in vitro and in vivo. Herein, we developed a new apoptosis imaging technology
      via a direct visualization of active caspase-3/-7 activity in living cells. For
      this, we synthesized a caspase-3/-7-specific cleavable peptide (KGDEVD)
      conjugated triacetylated N-azidoacetyl-D-mannosamine (Apo-S-Ac3ManNAz), wherein
      the Apo-S-Ac3ManNAz can be cleaved by the active caspase-3/-7 in live apoptotic
      cells and the cleaved Ac3ManNAz molecules can further generate targetable azido
      groups (N3) on the living cell surface. Importantly, the azido groups on the
      apoptotic tumor cells could be visualized with Cy5.5-conjugated
      dibenzylcyclooctyne (DBCO-Cy5.5) via bioorthogonal click chemistry in vitro cell
      culture condition and in vivo tumor-bearing mice. Therefore, our Apo-S-Ac3ManNAz
      can be utilized for the further applications in tumor therapy as a monitoring
      tool for anticancer efficacy and optimization of anticancer new drugs in cell
      culture system and in tumor-bearing mice.

PMID- 29192290
TI  - Direct conversion of human fibroblasts into hepatocyte-like cells by ATF5, PROX1,
      FOXA2, FOXA3, and HNF4A transduction.
AB  - Recently, it has been reported that human hepatocyte-like cells can be generated
      from fibroblasts by direct reprogramming technology. However, the conversion
      efficiency of human induced hepatocyte-like cells (hiHeps) is not high enough. In
      addition, comparative analysis with the existing models of hepatocytes, such as
      human iPS cell-derived hepatocyte-like cells and primary human hepatocytes, has
      not been sufficiently carried out. In this study, we screened hepatic
      transcription factors for efficient direct hepatic reprogramming and compared
      hepatic functions between hiHeps and other existing hepatocyte models. We found
      that human fibroblasts were efficiently converted into hiHeps by using a
      combination of ATF5, PROX1, FOXA2, FOXA3, and HNF4A (albumin+/alpha-1
      antitrypsin+ cells = 27%, asialoglycoprotein receptor 1+ cells = 22%). The CYP
      expression levels and CYP activities in hiHeps were higher than those in human
      iPS cell-derived hepatocyte-like cells, but lower than those in short-term (4 hr)
      cultured primary human hepatocytes and primary human hepatocytes collected
      immediately after thawing. These results suggested that functional hiHeps could
      be efficiently generated by ATF5, PROX1, FOXA2, FOXA3, and HNF4A transduction. We
      believe that hiHeps generated by our method will be useful for the drug-discovery
      activities such as hepatotoxicity screening and drug metabolism tests.

PMID- 29192292
TI  - Association between central papilla recession and gingival and interdental smile
      line.
AB  - OBJECTIVE: Interdental soft tissues play a critical role in pink esthetics. The
      presence and preservation of the interdental papillae in the esthetic zone is as
      crucial as the shape and contour of the anterior teeth in achieving an
      esthetically pleasing smile. The present study determines the association of
      central papilla recession with gingival and interdental smile line in
      periodontally healthy patients of different age groups. METHOD AND MATERIALS: The
      present study included 200 patients equally divided into 21 to 40 years and 41 to
      60 years age groups. The clinical and photographic evaluation of the central
      papilla, with midfacial gingiva, and its relationship with the vermilion border
      was performed. RESULTS: In total, 137 patients exhibited presence of central
      papilla, whilst 63 patients had central papilla recession with variable extent.
      The male patients predominantly had presence of central papilla in both the age
      groups, with 86% and 64%, compared with 74% and 50% in females, respectively.
      High gingival smile line was seen in the majority of the patients (62%), and this
      trend was similar to high interdental smile line (82% of the patients).
      CONCLUSION: Esthetics is affected in individuals having papilla recession along
      with high gingival smile line and interdental smile line as compared to
      individuals with low or cupid bow gingival smile line and interdental smile line.

PMID- 29192287
TI  - Next generation antibody drugs: pursuit of the 'high-hanging fruit'.
AB  - Antibodies are the most rapidly growing drug class and have a major impact on
      human health, particularly in oncology, autoimmunity and chronic inflammatory
      diseases. Many of the best understood and most tractable cell surface and
      secreted targets with known roles in human diseases have been extensively
      exploited for antibody drug development. In this Review, we focus on emerging and
      novel mechanisms of action of antibodies and innovative targeting strategies that
      could extend their therapeutic applications, including antibody-drug conjugates,
      bispecific antibodies and antibody engineering to facilitate more effective
      delivery. These strategies could enable the pursuit of difficult to hit, less
      well-understood or previously undruggable targets - the 'high-hanging fruit'.

PMID- 29192291
TI  - Kif1bp loss in mice leads to defects in the peripheral and central nervous system
      and perinatal death.
AB  - Goldberg-Shprintzen syndrome is a poorly understood condition characterized by
      learning difficulties, facial dysmorphism, microcephaly, and Hirschsprung
      disease. GOSHS is due to recessive mutations in KIAA1279, which encodes kinesin
      family member 1 binding protein (KIF1BP, also known as KBP). We examined the
      effects of inactivation of Kif1bp in mice. Mice lacking Kif1bp died shortly after
      birth, and exhibited smaller brains, olfactory bulbs and anterior commissures,
      and defects in the vagal and sympathetic innervation of the gut. Kif1bp was found
      to interact with Ret to regulate the development of the vagal innervation of the
      stomach. Although newborn Kif1bp -/- mice had neurons along the entire bowel, the
      colonization of the gut by neural crest-derived cells was delayed. The data show
      an essential in vivo role for KIF1BP in axon extension from some neurons, and the
      reduced size of the olfactory bulb also suggests additional roles for KIF1BP. Our
      mouse model provides a valuable resource to understand GOSHS.

PMID- 29192293
TI  - Digital evaluation of the fit of zirconia-reinforced lithium silicate crowns with
      a new three-dimensional approach.
AB  - OBJECTIVE: Several methods for the evaluation of fit of computer-aided
      design/computer-assisted manufacture (CAD/CAM)-fabricated restorations have been
      described. In the study, digital models were recorded with an intraoral scanning
      device and were measured using a new three-dimensional (3D) computer technique to
      evaluate restoration internal fit. The aim of the study was to evaluate the
      internal adaptation and fit of chairside CAD/CAM-fabricated zirconia-reinforced
      lithium silicate ceramic crowns fabricated with different post-milling protocols.
      The null hypothesis was that different post-milling protocols did not influence
      the fitting accuracy of zirconia-reinforced lithium silicate restorations. METHOD
      AND MATERIALS: A master all-ceramic crown preparation was completed on a
      maxillary right first molar on a typodont. Twenty zirconia-reinforced lithium
      silicate ceramic crowns (Celtra Duo, Dentsply Sirona) were designed and milled
      using a chairside CAD/CAM system (CEREC Omnicam, Dentsply Sirona). The 20 crowns
      were randomly divided into two groups based on post-milling protocols: no
      manipulation after milling (Group MI) and oven fired-glazing after milling (Group
      FG). A 3D computer method was used to evaluate the internal adaptation of the
      crowns. This was based on a subtractive analysis of a digital scan of the crown
      preparation and a digital scan of the thickness of the cement space over the
      crown preparation as recorded by a polyvinylsiloxane (PVS) impression material.
      The preparation scan and PVS scan were matched in 3D and a 3D difference analysis
      was performed with a software program (OraCheck, Cyfex). Three areas of internal
      adaptation and fit were selected for analysis: margin (MA), axial wall (AX), and
      occlusal surface (OC). Statistical analysis was performed using 80% percentile
      and one-way ANOVA with post-hoc Scheffe test (P = .05). RESULTS: The closest
      internal adaptation of the crowns was measured at the axial wall with 102.0 +/-
      11.7 um for group MI-AX and 106.3 +/- 29.3 um for group FG-AX. The largest
      internal adaptation of the crowns was measured for the occlusal surface with
      258.9 +/- 39.2 um for group MI-OC and 260.6 +/- 55.0 um for group FG-OC. No
      statistically significant differences were found for the post-milling protocols
      (P > .05). The 3D difference pattern was visually analyzed for each area with a
      color-coded scheme. CONCLUSION: Post-milling processing did not affect the
      internal adaptation of zirconia-reinforced lithium silicate crowns fabricated
      with a chairside CAD/CAM technique. The new 3D computer technique for the
      evaluation of fit of restorations may be highly promising and has the opportunity
      to be applied to clinical studies.

PMID- 29192294
TI  - Primary burning mouth syndrome: Literature review and preliminary findings
      suggesting possible association with pain modulation.
AB  - Primary burning mouth syndrome (BMS) is a chronic pain of a burning quality
      affecting the tongue and intraoral mucosa. Currently, there are no definite
      diagnostic criteria; therefore, the diagnosis is made by exclusion of potential
      local and systemic causes that could justify the burning sensation. The etiology
      behind primary BMS remains unclear; however, the most acceptable theories link
      primary BMS with neuropathic pain. This article provides a review of primary BMS
      diagnosis, mechanisms, and treatment with focus on the association of BMS with
      pain modulation. Preliminary data are presented suggesting a link between primary
      BMS and a faulty inhibitory pain system.

PMID- 29192295
TI  - High-performance liquid chromatography mass spectrometry of gold and alloy
      clusters protected by hydrophilic thiolates.
AB  - In this work, we found two hydrophilic interaction liquid chromatography (HILIC)
      columns for high-performance liquid chromatography (HPLC) suitable for the high
      resolution separation of hydrophilic metal clusters. The mass distributions of
      the product mixtures of hydrophilic metal clusters were evaluated via HPLC mass
      spectrometry (LC/MS) using these HILIC columns. Consequently, we observed
      multiple clusters that had not been previously reported for glutathionate (SG)
      protected gold clusters (Aun(SG)m). Additionally, we demonstrated that Aun
      xMx(SG)m alloy clusters (M = Ag, Cu, or Pd) in which part of the Au in the
      Aun(SG)m cluster is replaced by a heteroelement can be synthesized, similar to
      the case of hydrophobic alloy clusters. It is easy to evaluate the mass
      distributions of hydrophilic metal clusters using this method. Thus, remarkable
      progress in the synthesis techniques of hydrophilic metal clusters through the
      use of this method is anticipated, as is the situation for hydrophobic metal
      clusters.

PMID- 29192296
TI  - Reaction mechanism of hydrogen evolution catalysed by Co and Fe complexes
      containing a tetra-dentate phosphine ligand - a DFT study.
AB  - The reaction mechanism of the electro-catalytic proton reduction in neutral
      phosphate buffer enabled by mononuclear cobalt and iron complexes containing a
      tetra-dentate phosphine ligand (MP4N2, M = Fe, Co) has been elucidated by density
      functional calculations. The phosphate from the buffer was found to play a
      crucial role by coordinating to the metal and delivering a proton to the metal
      hydride in the H-H bond formation. For the more efficient cobalt catalyst, the
      starting species is a CoII complex with a hydrogen phosphate and a water molecule
      ligated at the two vacant coordination sites. Two sequential proton-coupled
      electron transfer reductions lead to the formation of a CoII-H intermediate with
      a dihydrogen phosphate ligand, and the reduction potentials for these two steps
      were calculated to be -0.58 V and -0.72 V, respectively. Subsequently, the H-H
      bond formation takes place via coupling of the CoII-H and the proton from the
      dihydrogen phosphate ligand. The total barrier was calculated to be 18.2 kcal mol
      1 with an applied potential of -0.5 V, which can further decrease to only 11.2
      kcal mol-1 with an applied potential of -0.8 V. When the phosphate is displaced
      by a water molecule, the total barrier for the dihydrogen formation increases by
      7.3 kcal mol-1. For the iron catalyst, the overall mechanism is essentially the
      same; however, the first reduction (FeII/FeI, potential of -1.13 V) is likely the
      rate-limiting step. The calculated results are in good agreement with the
      experimental data, which showed an onset potential of -0.50 V for the cobalt
      complex and -1.03 V for the iron complex.

PMID- 29192297
TI  - Rapid spheroid clearing on a microfluidic chip.
AB  - Spheroids are three-dimensional (3D) cell cultures that aim to bridge the gap
      between the use of whole animals and cellular monolayers. Microfluidics is
      regarded as an enabling technology to actively control the chemical environment
      of 3D cell cultures. Although a wide variety of platforms have been developed to
      handle spheroid cultures, the development of analytical systems for spheroids
      remains a major challenge. In this study, we engineered a microfluidic large
      scale integration (mLSI) chip platform for tissue-clearing and imaging. To enable
      handling and culturing of spheroids on mLSI chips, with diameters within hundreds
      of microns, we first developed a general rapid prototyping procedure, which
      allows scaling up of the size of pneumatic membrane valves (PMV). The presented
      prototyping method makes use of milled poly(methylmethacrylate) (PMMA) molds for
      obtaining semi-circular microchannels with heights up to 750 MUm. Semi-circular
      channel profiles are required for the functioning of the commonly used PMVs in
      normally open configuration. Height limits to tens of microns for this channel
      profile on photolithographic molds have hampered the application of 3D tissue
      models on mLSI chips. The prototyping technique was applied to produce an mLSI
      chip for miniaturization, automation, and integration of the steps involved in
      the tissue clearing method CLARITY, including spheroid fixation, acrylamide
      hydrogel infiltration, temperature-initiated hydrogel polymerization, lipid
      extraction, and immuno-fluorescence staining of the mitochondrial protein COX-IV,
      and metabolic enzyme GAPDH. Precise fluidic control over the liquids in the
      spheroid culturing chambers allowed implementation of a local hydrogel
      polymerization reaction, exclusively within the spheroid tissue. Hydrogel
      embedded spheroids undergo swelling and shrinkage depending on the pH of the
      surrounding buffer solution. A pH-jump from 8.5 to 5.5 shrinks the hydrogel
      embedded spheroid volume by 108% with a rate constant of 0.36 min-1. The process
      is reversible upon increasing the pH, with the rate constant for the shrinkage
      being -0.12 min-1. Repetitive cycling of the pH induces an osmotic flow within
      the hydrogel-embedded spheroid. Thirty cycles, performed in a total time interval
      of 10 minutes on-chip, reduced the clearing time of a hydrogel-embedded spheroid
      (with a diameter of 200 MUm) from 14 days to 5 hours. Therefore, we developed a
      physicochemical method to decrease the clearing time of hydrogel-embedded
      tissues. While the osmotic pump mechanism is an alternative to electrophoretic
      forces for decreasing tissue clearing times, the integration of the CLARITY
      method on chip could enable high throughput imaging with 3D tissue cultures.

PMID- 29192298
TI  - The bond rupture force for sulfur chains calculated from quantum chemistry
      simulations and its relevance to the tensile strength of vulcanized rubber.
AB  - From quantum chemistry simulations using density functional theory, we obtain the
      total electronic energy of an eight-atom sulfur chain as its end-to-end distance
      is extended until S-S bond rupture occurs. We find that a sulfur chain can be
      extended by about 40% beyond its nominally straight conformation, where it
      experiences rupture at an end-to-end tension of about 1.5 nN. Using this rupture
      force as the chain failure limit in an explicit polymer network simulation model
      (EPnet), we predict the tensile failure stress for sulfur crosslinked
      (vulcanized) natural rubber. Quantitative agreement with published experimental
      data for the failure stress is obtained in these simulations if we assume that
      only about 30% of the sulfur chains produce viable network crosslinks.
      Surprisingly, we also find that the failure stress of a rubber network does not
      scale linearly with the chain failure force limit.

PMID- 29192300
TI  - Characterizing an Ultra-High-Risk Subset of Patients With Hypopharynx and Larynx
      Cancer: The Power of Lymph Node Burden.

PMID- 29192301
TI  - Vision Loss Secondary to Autologous Adipose Stem Cell Injections: A Rising
      Problem.

PMID- 29192299
TI  - Machine learning to detect signatures of disease in liquid biopsies - a user's
      guide.
AB  - New technologies that measure sparse molecular biomarkers from easily accessible
      bodily fluids (e.g. blood, urine, and saliva) are revolutionizing disease
      diagnostics and precision medicine. Microchip devices can measure more disease
      biomarkers with better sensitivity and specificity each year, but clinical
      interpretation of these biomarkers remains a challenge. Single biomarkers in
      'liquid biopsy' often cannot accurately predict the state of a disease due to
      heterogeneity in phenotype and disease expression across individuals. To address
      this challenge, investigators are combining multiplexed measurements of different
      biomarkers that together define robust signatures for specific disease states.
      Machine learning is a useful tool to automatically discover and detect these
      signatures, especially as new technologies output increasing quantities of
      molecular data. In this paper, we review the state of the field of machine
      learning applied to molecular diagnostics and provide practical guidance to use
      this tool effectively and to avoid common pitfalls.

PMID- 29192302
TI  - Efficacy of Medicaid for Patients With Cancer in California.

PMID- 29192303
TI  - Association Between Ophthalmologist Age and Unsolicited Patient Complaints.
AB  - Importance: Understanding the distribution of patient complaints by physician age
      may provide insight into common patient concerns characteristic of early, middle,
      and late stages of careers in ophthalmology. Most previous studies of patient
      dissatisfaction have not addressed the association with physician age or
      controlled for other characteristics (eg, practice setting, subspecialty) that
      may contribute to the likelihood of patient complaints, unsafe care, and
      lawsuits. Objective: To assess the association between ophthalmologist age and
      the likelihood of generating unsolicited patient complaints (UPCs) among a cohort
      of ophthalmologists. Design, Setting, and Participants: Retrospective cohort
      study with variable duration of follow-up. The study assessed time to first
      complaint between 2002 and 2015 in 1342 attending ophthalmologists or neuro
      ophthalmologists who had graduated from medical school before 2010 and were
      affiliated with an organization that participates in Vanderbilt University
      Medical Center's Patient Advocacy Reporting System. Participants were stratified
      into 5 age bands and were followed up from the time of their employment to
      receipt of their first complaint. Trained coders categorized UPCs into 34
      specific types under 6 major categories. Main Outcomes and Measures: Time to
      first recorded complaint. Multivariable Cox proportional hazards model was used
      to measure the association between time to first complaint and ophthalmologist
      age after adjustment for predetermined covariates. Results: The median physician
      age was 47 years, with 9% who were 71 years or older. The cohort was 74% male,
      90% held MD degrees, and 73% practiced in academic medical centers. The mean
      follow-up period was 9.8 years. Ophthalmologists older than 70 years had the
      lowest complaint rate (0.71 per 1000 follow-up days vs 1.41, 1.84, 2.02, and 1.88
      in descending order of age band). By 2000 days of follow-up (or within 5.5
      years), the youngest group had an estimated UPC risk of 0.523. By 4000 days (>10
      years), participants in the older than 70 years age band had an estimated risk of
      UPC of only 0.364. The 2 youngest age bands were associated with a statistically
      significant shorter time to first complaint. Compared with those aged 71 years or
      older, the risk of incurring a UPC for those aged 41 to 50 years was 1.73-fold
      higher (hazard ratio [HR], 1.73; 95% CI, 1.21-2.46; P = .002). Similarly,
      participants aged 31 to 40 years had a 2.36 times higher risk of incurring a UPC
      (HR, 2.36; 95% CI, 1.64-3.40; P < .001). Conclusions and Relevance: This study
      suggests that older ophthalmologists are less likely to receive UPCs than younger
      ones. Although limitations in the study design could affect the interpretation of
      these conclusions, the findings may have practical implications for patient
      safety, clinical education, and clinical practice management.

PMID- 29192304
TI  - Association of Hearing Loss and Otologic Outcomes With Fibrous Dysplasia.
AB  - Importance: Fibrous dysplasia (FD) and McCune-Albright syndrome (MAS) are rare
      bone and endocrine disorders in which expansile fibro-osseous lesions result in
      deformity, pain, and functional impairment. The effect of FD on hearing and
      otologic function has not been established. Objectives: To characterize
      audiologic and otologic manifestations in a large cohort of individuals with
      FD/MAS and to investigate potential mechanisms of hearing loss. Design, Setting,
      and Participants: In this natural history study, individuals with craniofacial FD
      seen at a clinical research center underwent clinical, biochemical, computed
      tomographic, audiologic, and otolaryngologic evaluations. Main Outcomes and
      Measures: Clinical and radiologic features associated with hearing loss and
      otologic disease were evaluated. Conductive hearing loss was hypothesized to be
      associated with narrowing of the external auditory canal (EAC), FD involving the
      epitympanum, and FD crowding the ossicular chain. Sensorineural hearing loss was
      hypothesized to be associated with FD affecting the internal auditory canal (IAC)
      and otic capsule. Results: Of the 130 study participants with craniofacial FD who
      were evaluated, 116 (89.2%) had FD that involved the temporal bone (median age,
      19.6 years; range, 4.6-80.3 years; 64 female [55.2%]), whereas 14 (10.8%) had
      craniofacial FD that did not involve the temporal bone. Of the 183 ears with
      temporal bone FD, hearing loss was identified in 41 ears (22.4%) and was
      conductive in 27 (65.9%), sensorineural in 12 (29.3%), and mixed in 2 (4.9%).
      Hearing loss was mild and nonprogressive in most participants. Whereas EACs were
      narrower in ears with FD (mean difference [MD], 0.33 mm; 95% CI, 0.11-0.55 mm),
      this finding was associated with conductive hearing loss in only 4 participants.
      Fibrous dysplasia crowding of the ossicles was associated with conductive hearing
      loss (odds ratio [OR], 5.0; 95% CI, 2.1-11.6). The IAC length was not different
      between ears with and without FD (MD, -0.37; 95% CI, -0.95 to 0.211); however,
      canals were elongated in ears with sensorineural hearing loss (MD, -1.33; 95% CI,
      -2.60 to -0.07). Otic capsule involvement was noted in only 4 participants, 2 of
      whom had sensorineural hearing loss. Both MAS-associated growth hormone excess
      (OR, 3.1; 95% CI, 1.3-7.5) and neonatal hypercortisolism (OR, 11; 95% CI, 2.5-55)
      were associated with an increased risk of hearing loss . Conclusions and
      Relevance: Hearing loss in craniofacial FD is common and mild to moderate in most
      individuals. It typically arises from FD crowding of the ossicular chain and
      elongation of the IAC, whereas EAC stenosis and otic capsule invasion are less
      common causes. Individuals with craniofacial FD should undergo otolaryngologic
      evaluation and monitoring, including assessment to identify those with high-risk
      features.

PMID- 29192305
TI  - Association of Quantitative Metastatic Lymph Node Burden With Survival in
      Hypopharyngeal and Laryngeal Cancer.
AB  - Importance: Nodal staging for laryngohypopharyngeal cancers is based primarily on
      size and laterality, with less value placed on absolute number of metastatic
      lymph nodes (LNs). We are aware of no studies to date that have specifically
      addressed the prognostic effect of quantitative nodal burden in larynx or
      hypopharynx malignancies. Objective: To assess the independent impact of
      quantitative metastatic LN burden on mortality risk. Design, Setting, and
      Participants: Univariate and multivariable models were constructed to evaluate
      the association between patients' number of metastatic LNs and their survival,
      adjusting for factors such as nodal size, laterality, extranodal extension,
      margin status, and adjuvant treatment. Participants were patients with squamous
      cell carcinoma of the larynx or hypopharynx undergoing upfront surgical resection
      for curative intent at a US hospital between 2004 and 2013, as identified in the
      National Cancer Database. A neck dissection of a minimum of 10 LNs was required.
      Main Outcomes and Measures: Overall survival. Results: Overall, 8351 cases were
      included (mean [SD] age, 61 [10.1] years; 6499 men [77.8%]; 4710 patients with
      metastatic LNs and 3641 with no metastatic LNs). Mortality risk escalated
      continuously without plateau as number of metastatic nodes increased, with the
      hazard per node (hazard ratio [HR], 1.19; 95% CI, 1.16-1.23; P < .001) most
      pronounced up to 5 positive LNs. Extranodal extension was also associated with
      increased mortality (HR, 1.34; 95% CI, 1.13-1.59; P < .001). Increasing number of
      nodes examined was associated with improved survival, albeit to a lesser degree
      (per 10 LNs: HR, 0.97; 95% CI, 0.96-0.98; P < .001) and without a detectable
      change point. Other nodal factors, including nodal size, contralateral LN
      involvement (TNM stage N2c), and lower LN involvement (levels 4-5), were not
      associated with mortality in multivariable models when accounting for number of
      positive LNs. A novel, parsimonious nodal staging system derived by recursive
      partitioning analysis exhibited greater concordance with survival than the TNM
      staging system outlined in the American Joint Committee on Cancer's AJCC Staging
      Manual, 8th edition. Conclusions and Relevance: The number of metastatic nodes is
      a predominant independent factor associated with mortality in hypopharyngeal and
      laryngeal cancers. Moreover, standard nodal staging factors like LN size and
      contralaterality have no independent prognostic value when accounting for
      positive LN number. Deeper integration of quantitative metastatic nodal disease
      may simplify staging and better triage the need for adjuvant therapy.

PMID- 29192306
TI  - Asymptomatic Septal Mass.

PMID- 29192307
TI  - Trends in Cancer Survival by Health Insurance Status in California From 1997 to
      2014.
AB  - Importance: There have been substantial improvements in the early detection,
      treatment, and survival from cancer in the United States, but it is not clear to
      what extent patients with different types of health insurance have benefitted
      from these advancements. Objective: To examine trends in cancer survival by
      health insurance status from January 1997 to December 2014. Design, Setting, and
      Participants: California Cancer Registry (a statewide cancer surveillance system)
      data were used to estimate population-based survival by health insurance status
      in 3 calendar periods: January 1997 to December 2002, January 2003 to December
      2008, and January 2009 to December 2014 with follow-up through 2014. Overall, 1
      149 891 patients diagnosed with breast, prostate, colorectal, or lung cancer, or
      melanoma in California were included in the study. Main Outcomes and Measures:
      Five-year all-cause and cancer-specific survival probabilities by insurance
      category and calendar period for each cancer site and sex; hazard ratios (HRs)
      and 95% CIs for each insurance category (none, Medicare, other public) compared
      with private insurance in each calendar period. Results: According to data from 1
      149 891 patients diagnosed with breast, prostate, colorectal, or lung cancer, or
      melanoma gathered from the California Cancer Registry, improvements in survival
      were almost exclusively limited to patients with private or Medicare insurance.
      For patients with other public or no insurance, survival was largely unchanged or
      declined. Relative to privately insured patients, cancer-specific mortality was
      higher in uninsured patients for all cancers except prostate, and disparities
      were largest from 2009 to 2014 for breast (HR, 1.72; 95% CI, 1.45-2.03), lung
      (men: HR, 1.18; 95% CI, 1.06-1.31 and women: HR, 1.32; 95% CI, 1.15-1.50), and
      colorectal cancer (women: HR, 1.30; 95% CI, 1.05-1.62). Mortality was also higher
      for patients with other public insurance for all cancers except lung, and
      disparities were largest from 2009 to 2014 for breast (HR, 1.25; 95% CI, 1.17
      1.34), prostate (HR, 1.17; 95% CI, 1.04-1.31), and colorectal cancer (men: HR,
      1.16; 95% CI, 1.08-1.23 and women: HR, 1.11; 95% CI, 1.03-1.20). Conclusions and
      Relevance: After accounting for patient and clinical characteristics, survival
      disparities for men with prostate cancer and women with lung or colorectal cancer
      increased significantly over time, reflecting a lack of improvement in survival
      for patients with other public or no insurance. To mitigate these growing
      disparities, all patients with cancer need access to health insurance that covers
      all the necessary elements of health care, from prevention and early detection to
      timely treatment according to clinical guidelines.

PMID- 29192308
TI  - Intraorbital Bullet.

PMID- 29192309
TI  - Zoledronic Acid Dosing in Patients With Metastatic Breast Cancer.

PMID- 29192310
TI  - Medical Preprints-A Debate Worth Having.

PMID- 29192311
TI  - Peak Nasal Inspiratory Flow as an Objective Measure of Nasal Obstruction and
      Functional Septorhinoplasty Outcomes.

PMID- 29192313
TI  - The shape of novel objects contributes to shared impressions.
AB  - How do people share impressions of novel objects, and is this even possible? We
      tested whether the shape of novel 3-D objects can lead to similar impressions
      across people. To do this, we introduced a technique for manipulating highly
      complex shapes and measured four types of evaluative impressions (approachable,
      dangerous, beautiful, likable). Because relatively little is understood regarding
      how people form impressions of novel objects, we first sought to confirm the
      reliability of this behavior by examining how similar impressions are for an
      individual asked to re-evaluate the stimuli (i.e., impression consistency). To
      situate the magnitude of reliability, we compared novel objects to faces-familiar
      and extensively studied stimuli. Impression consistency was always present for
      both types of stimuli and comparable across all evaluations. Second, and more
      importantly, we tested how similar impressions are across people (i.e.,
      impression consensus). Impression consensus was always present for faces, but not
      always for novel objects. In Study 2 we examined a greater diversity of shapes
      and replicated the findings of Study 1 for novel objects. The findings suggest
      that impression consensus for novel objects only emerges when certain types of
      shapes and evaluations map together. When such mapping is possible, impressions
      are isomorphic with the parametrized shapes.

PMID- 29192312
TI  - Association of Lymph Node Density With Survival of Patients With Papillary
      Thyroid Cancer.
AB  - Importance: Lymph node metastases are common in papillary thyroid cancer (PTC),
      yet the impact of nodal metastases on survival remains unclear. Lymph node
      density (LND) is the ratio between the number of positive lymph nodes excised and
      the total number of excised lymph nodes. Lymph node density has been suggested as
      a prognostic factor in many types of cancer. Objective: To evaluate the
      prognostic role of LND in PTC. Design, Setting, and Participants: This cohort
      study reviewed medical records of patients with PTC who were treated at the
      University of Texas MD Anderson Cancer Center between January 1, 2000, and
      December 31, 2015. Survival and recurrence outcomes were calculated by using the
      Kaplan-Meier method. Significant variables on univariate analysis were subjected
      to a Cox proportional hazards regression multivariate model. Main Outcomes and
      Measures: Primary study outcome was disease-specific survival (DSS); other
      measurements included overall survival (OS). Results: The study cohort included
      data for 2542 patients (1801 [71%] male; median age, 48 years [range, 18-97
      years]) with a median follow-up of 55 months (range, 4-192 months). The 10-year
      disease-specific survival rate was 98% for patients with LND of 0.19 or less,
      compared with 90% for those with LND greater than 0.19 (effect size, 8%; 95% CI,
      4%-15%). The 10-year overall survival was 87% for patients with LND of 0.19 or
      less, compared with 79% for patients with LND greater than 0.19 (effect size, 8%;
      95% CI, 3%-15%). Multivariable analysis revealed that LND greater than 0.19 was
      independently associated with an adverse DSS (hazard ratio [HR], 4.11; 95% CI,
      2.11-8.97) and OS (HR, 1.96; 95% CI, 1.24-4.11). Subgroup analysis of patients
      with 18 or more lymph nodes analyzed revealed that LND greater than 0.19 remained
      a significant marker for DSS (HR, 2.94; 95% CI, 1.36-9.81) and OS (HR, 2.26; 95%
      CI, 1.12-5.34). Incorporating LND into the current American Joint Committee on
      Cancer staging system successfully stratified risk groups compared with the
      traditional TNM staging system. Conclusions and Relevance: This single-institute
      study demonstrates the reproducibility of LND as a predictor of outcomes in PTC.
      Lymph node density can potentially assist in identifying patients with poorer
      survival who may benefit from more aggressive adjuvant therapy.

PMID- 29192314
TI  - Contour junctions defined by dynamic image deformations enhance perceptual
      transparency.
AB  - The majority of work on the perception of transparency has focused on static
      images with luminance-defined contour junctions, but recent work has shown that
      dynamic image sequences with dynamic image deformations also provide information
      about transparency. The present study demonstrates that when part of a static
      image is dynamically deformed, contour junctions at which deforming and
      nondeforming contours are connected facilitate the deformation-based perception
      of a transparent layer. We found that the impression of a transparent layer was
      stronger when a dynamically deforming area was adjacent to static nondeforming
      areas than when presented alone. When contour junctions were not formed at the
      dynamic-static boundaries, however, the impression of a transparent layer was not
      facilitated by the presence of static surrounding areas. The effect of the
      deformation-defined junctions was attenuated when the spatial pattern of
      luminance contrast at the junctions was inconsistent with the perceived
      transparency related to luminance contrast, while the effect did not change when
      the spatial luminance pattern was consistent with it. In addition, the results
      showed that contour completions across the junctions were required for the
      perception of a transparent layer. These results indicate that deformation
      defined junctions that involve contour completion between deforming and
      nondeforming regions enhance the perception of a transparent layer, and that the
      deformation-based perceptual transparency can be promoted by the simultaneous
      presence of appropriately configured luminance and contrast-other features that
      can also by themselves produce the sensation of perceiving transparency.

PMID- 29192315
TI  - Clinical Factors Associated With Reoperation and Prolonged Length of Stay in Free
      Tissue Transfer to Oncologic Head and Neck Defects.
AB  - Importance: Prolonged hospitalization and reoperation after free tissue transfer
      may be associated with certain clinical factors. Objective: To determine patient
      and surgical factors associated with length of stay (LOS) and reoperation
      following surgical procedures for malignant neoplasm of the head and neck
      involving microvascular free tissue transfer reconstruction. Design, Setting, and
      Participants: This was a retrospective review of American College of Surgeons
      National Surgical Quality Improvement Program data from 2012 to 2014 using
      International Classification of Diseases, Ninth Revision (ICD-9), codes for
      malignant neoplasms of the head and neck. Multivariable logistic regression
      modeling was used to examine correlation of patient and surgical variables with
      reoperation and LOS. The national retrospective database included outcomes from
      community and academic participant hospitals (517 member institutions in 2014). A
      total of 1115 cases of head and neck malignant neoplasm ablation with
      microvascular free tissue transfer flap were reviewed retrospectively. Main
      Outcomes and Measures: Incidence of reoperation within 30 days of index operation
      and hospitalization equal to or longer than 13.0 days, which is equal to being in
      the top quartile for duration of stay. Results: Of the 1115 patients, 370 (33.2)
      were female, and the mean (SD) age was 66.8 (3.9) years. Predictors of prolonged
      length of stay included return to the operating room (odds ratio [OR], 4.8; 95%
      CI, 3.3-6.9), smoking (OR, 2.1; 95% CI, 1.5-3.1), clean-contaminated wound (OR,
      2.2; 95% CI, 1.3-4.0), bony flap (OR, 1.8; 95% CI, 1.2-2.8), age (OR, 1.5; 95%
      CI, 1.2-1.7), and operative time (OR, 1.2; 95% CI, 1.1-1.3). Reoperation occurred
      298 times for 225 patients (20.2%). Mean (SD) time to reoperation was 8.0 (7.7)
      days, with 180 (80%) occurring before discharge from the primary operation. The
      most common indications for reoperation were neck exploration (37 [12.4%]) or
      incision and drainage of neck (35 [11.7%]). Conclusions and Relevance: American
      College of Surgeons National Surgical Quality Improvement Program data allow for
      large database analysis of free flap transfer to the head and neck. The data
      herein provide information to help guide surgeons on which patients will require
      longer stay in hospital and the most common reasons for return to the operating
      room. Wound class of index operation, subsequent wound-related complications, and
      long duration of the index operation were the primary drivers of increased risk
      for reoperation and, therefore, prolonged hospitalization. These same factors
      were also associated with prolonged hospitalization without reoperation. Level of
      Evidence: NA.

PMID- 29192316
TI  - The Importance of Continued US Investment to Sustain Momentum Toward Global
      Health Security.

PMID- 29192317
TI  - Zoledronic Acid Dosing in Patients With Metastatic Breast Cancer.

PMID- 29192318
TI  - The Influence of Target and Masker Characteristics on Infants' and Adults'
      Detection of Speech.
AB  - Purpose: Several investigators have compared infants' detection of speech in
      speech and nonspeech maskers to evaluate developmental differences in masking.
      Such comparisons have produced contradictory results, possibly because each
      investigation used different stimuli. The current study examined target and
      masker effects on infants' and adults' detection of speech. Method: An observer
      based procedure was used to compare infants' and adults' detection of the vowel
      /v/ and the word "baby" in a 2-talker speech masker and matched speech-spectrum
      noise. The measure of performance was d'. A total of 43 7-month-old infants and
      41 young adults were randomly assigned to 1 target-masker combination condition,
      and mean performance was compared across conditions at each age. Results: Adults'
      detection was influenced by an interaction between the target and the masker:
      Adults detected the vowel better in the 2-talker masker than in speech-spectrum
      noise but detected the word equally well in the 2 maskers. In contrast, infants
      detected both targets better in speech-spectrum noise than in the 2-talker
      masker. Conclusions: The relative effects of the masker on target detection by
      infants and adults depend on the target to be detected. Thus, conclusions drawn
      about differences between infants and adults in the mechanisms responsible for
      masking will depend on the stimuli. Standardization of speech stimuli in
      developmental research would help clarify the nature of infants' segregation
      difficulties. Supplemental Material: https://doi.org/10.23641/asha.5613139.

PMID- 29192319
TI  - Zoledronic Acid Dosing in Patients With Metastatic Breast Cancer-Reply.

PMID- 29192320
TI  - Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck
      squamous cell carcinoma cells.
AB  - The aim of the present study was to search for an effective regimen among
      existing chemotherapies for head and neck squamous cell carcinoma (HNSCC). Among
      the tested drugs, we focused on combined SN-38, which is the active metabolite
      produced from irinotecan hydrochloride - a type I DNA topoisomerase inhibitor -
      after it is metabolized by carboxylesterase in the liver and gefitinib, an EGFR
      tyrosine kinase inhibitor treatment, based on the ability of this combination to
      inhibit HNSCC cell growth. Contrary to our expectation, in vivo, there was no
      significant difference in tumor growth suppression between gefitinib-only
      treatment and gefitinib plus SN-38. However, when tumor measurements were
      continued after treatment ceased, we found that several tumors showed renewed
      growth in the gefitinib-only group. The tumors that resumed growing after
      treatment showed increased CD44 expression compared with tumors from the combined
      treatment group. Next, we investigated the mechanism whereby SN-38 and gefitinib
      inhibited CD44 expression in vitro. These studies revealed that the combined
      treatment promoted lysosomal degradation of CD44. The present study revealed that
      combined gefitinib and SN-38 treatment inhibits CD44 expression by promoting its
      lysosomal degradation in HNSCC cells. However, it is still unclear whether
      inhibition of CD44 expression in HNSCC cells can directly suppress tumor regrowth
      after therapy. Thus, it may be necessary to elucidate the relationship between
      the effects of these chemotherapeutic agents on CD44 expression and tumor
      recurrence/metastasis in future studies.

PMID- 29192321
TI  - miR-106b-5p promotes cell cycle progression of malignant melanoma by targeting
      PTEN.
AB  - This study investigated how miR-106b-5p/PTEN signaling affects the cell cycle of
      malignant melanoma (MM) cells. miR-106b-5p mRNA was identified with qRT-PCR.
      Through transient transfection, miR-106b-5p or PTEN was upregulated and
      downregulated in MM cells. With such transfected cells, MTT assay, colony
      formation assay and flow cytometry were carried out to investigate the role of
      miR-106b-5p in cell cycle progression after the transfected cells were treated
      with reverse-regulation of miR-106b-5p or PTEN. Western blot analysis was used to
      quantify all proteins, and a luciferase reporter assay was carried out to
      validate miR-106b-5p targeting PTEN. miR-106b-5p mRNA was overexpressed in MM
      tissues and cell lines. MM cells with upregulated miR-106b-5p presented faster
      growth and shorter cell cycles, while those with knockdown of miR-106b-5p
      presented the opposite trend. PTEN was subject to post-transcriptional regulation
      of miR-106b-5p. Based on such a finding, further exploration was carried out to
      investigate the interaction between cyclin D1 and P27Kip1, with the finding that
      miR-106b-5p can stimulate cyclin D1 and suppress P27Kip1 via the Akt/ERK pathway.
      The results of this study suggest that miR-106b-5p may be a promoter in MM
      progression, possibly by targeting PTEN and thus regulating the downstream cell
      cycle-related proteins and Akt/ERK pathway.

PMID- 29192322
TI  - omega3-polyunsaturated fatty acids induce cell death through apoptosis and
      autophagy in glioblastoma cells: In vitro and in vivo.
AB  - Among brain tumors, glioblastoma (GBM) is the most aggressive type and is
      associated with the lowest patient survival rate. Numerous lines of evidence have
      established that omega-3-polyunsaturated fatty acids (omega3-PUFAs) have
      potential for the prevention and therapy of several types of cancers.
      Docosahexaenoic acid (DHA), an omega3-PUFA, was reported to inhibit growth and
      induce apoptotic and autophagic cell death in several cancer cell lines; however,
      its effects on GBM cells are still unknown. in the present study, we examined the
      cytotoxic effect of DHA on the GBM cell lines, D54MG, U87MG, U251MG and GL261.
      Treatment of GBM cells with DHA induced PARP cleavage, increased the population
      of sub-G1 cells, and increased the number of TUNEL-positive cells, which are all
      indicative of apoptosis. Furthermore, treatment of GBM cells with DHA resulted in
      a significant increase in autophagic activity, as revealed by increased LC3-II
      levels, GFP-LC3 puncta, and autophagic flux activation, accompanied by activation
      of 5'-AMP-activated protein kinase (AMPK) and decreases in phosphorylated Akt (p
      AktSer473) levels and mTOR activity. In vivo, endogenous expression of
      Caenorhabditis elegans omega3-desaturase, which converts omega6-PUFAs to omega3
      PUFAs, in fat-1 transgenic mice yielded a significant decrease in tumor volume
      following subcutaneous injection of mouse glioma cells (GL261), when compared
      with wild-type mice. TUNEL-positive cell numbers and LC3-II levels were elevated
      in tumor tissue from the fat-1 transgenic mice compared with tumor tissue from
      the wild-type mice. In addition, p-Akt levels were decreased and p-AMPK levels
      were increased in tumor tissue from the fat-1 transgenic mice. These results
      indicate that omega3-PUFAs induce cell death through apoptosis and autophagy in
      GBM cells; thus, it may be possible to use omega3-PUFAs as chemopreventive and
      therapeutic agents for GBM.

PMID- 29192323
TI  - Significant inhibition of infantile hemangioma growth by sustained delivery of
      urea from liposomes-in-microspheres.
AB  - Infantile hemangioma (IH) is a benign pediatric tumor, and rapid growth of IH can
      result in serious morbidity and even mortality. Only one drug HemangeolTM
      (propranolol hydrochloride oral solution) has been approved for the treatment of
      IH, whereas patients suffer from its adverse effects and high frequency of
      administration. We have used urea, an organic compound and a normal body
      metabolite, in the treatment of IH for 20 years, and demonstrated that urea is an
      effective and well-tolerated treatment for IH. To reduce the daily administration
      of urea, we firstly utilized urea-loaded liposomes-in-microspheres (ULIM) as a
      novel topical controlled release system to realize the sustained release of urea.
      ULIM were fabricated from the encapsulation of urea-loaded liposomes in
      poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic
      acid) microspheres. The characteristics, activity and mechanism against IH of
      ULIM were examined in vitro and in vivo. ULIM were of a desired particle size
      (~62.4 um), drug encapsulation efficiency (~51.5%) and sustained drug release for
      40 days. ULIM inhibited the proliferation of hemangioma endothelia cells (HemECs)
      and expression of vascular endothelial growth factor-A in HemECs. The therapeutic
      effect of ULIM in IH was better than propranolol, urea, urea-loaded liposomes and
      urea-loaded microspheres in vivo, as reflected by markedly decreased hemangioma
      weight, volume and microvessel density. None of the treated mice showed
      behavioral changes, severe side-effects and weight loss. Our results suggest that
      use of ULIM is a potential and safe approach with which to locally and
      efficiently deliver urea to hemangioma, and is a promising alternative to
      propranolol in the treatment of IH.

PMID- 29192324
TI  - A novel mechanism of neovascularization in peritoneal dissemination via cancer
      associated mesothelial cells affected by TGF-beta derived from ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) is believed to cause peritoneum dissemination
      through microenvironmental cell-to-cell communication between the tumor and
      mesothelium, leading to the further acquisition of progressive and metastatic
      potentials. In the present study, we aimed to determine the role of cancer
      associated mesothelial cells (CAMCs) in the promotion of tumor neovascularization
      and vascular permeability via enhanced vascular endothelial growth factor (VEGF)
      production. We examined whether a characteristic morphological change in human
      peritoneal mesothelial cells (HPMCs) was observed in the presence of malignant
      ascites and tumor-derived TGF-beta. We focused on the enhanced production of VEGF
      in CAMCs and its crucial role in endothelial migration and tube formation. Normal
      HPMCs showed an epithelial morphology with a cobblestone appearance. When HPMCs
      were co-cultured with malignant ascites from patients with advanced EOC, a
      dramatic morphologic change was noted from an epithelioid pattern to an alpha-SMA
      positive fibroblastic, mesenchymal pattern. Additionally, we found that EOC
      derived TGF-beta induced typical EMT-like morphological alteration in HPMCs,
      which was associated with CAMCs. We further discovered that CAMCs play a crucial
      role in the enhanced migration and tube formation of endothelial cells by the
      promotion of VEGF production. In conclusion, our findings indicate the possible
      involvement of CAMCs in the neovascularization of EOC and enhancement of vascular
      permeability, resulting in the formation of malignant ascites. The novel
      mechanism of CAMCs as a facilitator of EOC progression is displayed by
      microenvironmental cell-to-cell communication between EOC and the mesothelium.

PMID- 29192325
TI  - Downregulation of microRNA-1274a induces cell apoptosis through regulation of
      BMPR1B in clear cell renal cell carcinoma.
AB  - Our previous studies of the microRNA (miRNA) expression signature in clear cell
      renal cell carcinoma (ccRCC) indicated that miRNA-1274a (miR-1274a) was
      significantly upregulated in clinical specimens, suggesting that miR-1274a may
      act as an oncogenic miRNA in ccRCC. The aim of this study was to investigate the
      functional roles of miR-1274a and identify downstream tumor-suppressive targets
      regulated by miR-1274a in ccRCC cells. Functional studies of miR-1274a were
      carried out by anti-miRNA to investigate cell proliferation and apoptosis using
      the A498, ACHN and Caki1 ccRCC cell lines. Suppression of miR-1274a significantly
      inhibited cancer cell proliferation and induced apoptosis in the ccRCC cells.
      Gene expression data combined with in silico analysis and luciferase reporter
      assays demonstrated that bone morphogenetic protein receptor type 1B (BMPR1B) was
      directly regulated by miR-1274a. Moreover, TCGA database as well as
      immunohistochemistry demonstrated low expression of BMPR1B in ccRCC clinical
      specimens compared to that in normal kidney tissues. We conclude that loss of
      oncogenic miR-1274a reduced cancer cell proliferation and induced apoptosis in
      ccRCC through targeting BMPR1B. Our data revealing molecular pathways and a
      target gene regulated by oncogenic miR-1274a provide new insight into the
      potential mechanisms of ccRCC oncogenesis.

PMID- 29192326
TI  - EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive
      cells via the BCR-ABL/PI3K/AKT/mTOR pathway.
AB  - Although the introduction of tyrosine kinase inhibitors greatly improved the
      survival of patients with chronic myeloid leukemia (CML), drug resistance remains
      a problem. Thus, mechanism-based novel therapeutic targets warrant exploration.
      Recently, epidermal growth factor receptor kinase substrate 8 (EPS8), which has
      been identified as an oncogene and plays an important role in a broad spectrum of
      solid tumours, was reported to be related to poor prognosis or chemoresistance in
      acute leukemia patients. However, its role in CML remains unclear. In the present
      study, using q-RT-PCR, we demonstrated that CML patients expressed a higher level
      of EPS8 mRNA in bone marrow mononuclear cells than healthy controls. Then, to
      determine the effect of EPS8 on the biological functions of CML cells, EPS8
      expression was knocked down in the human CML cell line K562. Reduced
      proliferation, increased apoptosis, impaired adhesion and migration were observed
      in K562 cells after EPS8 silencing. Notably, attenuation of EPS8 increased
      chemosensitivity both in imatinib-sensitive K562 cells and in the imatinib
      resistant murine BCR-ABL+ 32D-p210BCR/ABL-T315I cells. Mechanistically, knockdown
      of EPS8 downregulated p-BCR/ABL and its downstream AKT/mTOR signalling pathway.
      Finally, knockdown of EPS8 attenuated K562 cell proliferation in BALB/c nude
      mice. These data indicated that EPS8 regulated the proliferation, apoptosis and
      chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway.
      Targeting EPS8 alone or combined with a tyrosine kinase inhibitor may be a
      promising alternative therapeutic strategy.

PMID- 29192327
TI  - Characterization of etoposide- and cisplatin-chemoresistant retinoblastoma cell
      lines.
AB  - Retinoblastoma (RB) is the most common malignant intraocular tumor in early
      childhood. Imminent chemotherapy resistance diminishes the clinical-therapeutic
      options and emphasizes the necessity for new therapeutic approaches. The present
      study aimed at characterizing and comparing etoposide and cisplatin-resistant
      human RB cell lines with regard to changes in proliferation and apoptosis levels,
      anchorage independent growth behavior in vitro as well as tumor formation
      capacity in vivo. The proliferation rates were significantly increased in the
      etoposide-resistant RB cell lines Y-79, WERI-Rb1 and RB-355 reflecting
      significantly higher growth kinetics compared to the parental controls. In line
      with these findings in in vivo chicken chorioallantoic (CAM) assays, etoposide
      resistant cell lines generated significantly increased numbers of tumors with
      higher tumor weights compared to their parental counterparts. In contrast to
      etoposide, the cisplatin-resistant RB cell lines Y-79, WERI-Rb1 and RB-355
      displayed significantly increased apoptosis rates and reduced proliferation rates
      resulting in significantly decreased growth kinetics. Tumor formation capacity of
      cisplatin-resistant cell lines did not significantly change, and in comparison
      with parental controls cisplatin-resistant Y-79 cells displayed significantly
      reduced tumor weight. Soft agarose assays indicated that anchorage-independent
      growth of all chemotherapy-resistant cell lines analyzed was significantly
      decreased. Summarizing, one can state that etoposide-resistant RB cells behave
      more aggressively than the tumor cells of origin and potentially represent a risk
      factor for local relapse, while cisplatin-resistant cells show a significantly
      decreased tumorigenic potential.

PMID- 29192328
TI  - CRISPR/Cas9-mediated knockout of PiSSK1 reveals essential role of S-locus F-box
      protein-containing SCF complexes in recognition of non-self S-RNases during cross
      compatible pollination in self-incompatible Petunia inflata.
AB  - KEY MESSAGE: Function of Petunia PiSSK1. Self-incompatibility (SI), an inbreeding
      preventing mechanism, is regulated in Petunia inflata by the polymorphic S-locus,
      which houses multiple pollen-specific S-locus F-box (SLF) genes and a single
      pistil-specific S-RNase gene. S 2-haplotype and S 3-haplotype possess the same 17
      polymorphic SLF genes (named SLF1 to SLF17), and each SLF protein produced in
      pollen is assembled into an SCF (Skp1-Cullin1-F-box) E3 ubiquitin ligase complex.
      A complete suite of SLF proteins is thought to collectively interact with all non
      self S-RNases to mediate their ubiquitination and degradation by the 26S
      proteasome, allowing cross-compatible pollination. For each SCFSLF complex, the
      Cullin1 subunit (named PiCUL1-P) and Skp1 subunit (named PiSSK1), like the F-box
      protein subunits (SLFs), are pollen-specific, raising the possibility that they
      also evolved specifically to function in SI. Here we used CRISPR/Cas9-meditated
      genome editing to generate frame-shift indel mutations in PiSSK1 and examined the
      SI behavior of a T 0 plant (S 2 S 3) with biallelic mutations in the pollen
      genome and two progeny plants (S 2 S 2) each homozygous for one of the indel
      alleles and not carrying the Cas9-containing T-DNA. Their pollen was completely
      incompatible with pistils of seven otherwise-compatible S-genotypes, but fully
      compatible with pistils of an S 3 S 3 transgenic plant in which production of S3
      RNase was completely suppressed by an antisense S 3-RNase gene, and with pistils
      of immature flower buds, which produce little S-RNase. These results suggest that
      PiSSK1 specifically functions in SI and support the hypothesis that SLF
      containing SCF complexes are essential for compatible pollination.

PMID- 29192329
TI  - Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer
      patients.
AB  - PURPOSE: Despite advances in medical technology, radiation dermatitis occurs in
      95% of patients receiving radiation therapy (RT) for cancer. Currently, there is
      no standard and effective treatment for the prevention or control of radiation
      dermatitis. The goal of the study was to determine the efficacy of oral curcumin,
      one of the biologically active components in turmeric, at reducing radiation
      dermatitis severity (RDS) at the end of RT, using the RDS scale, compared to
      placebo. METHODS: This was a multisite, randomized, double-blinded, placebo
      controlled trial of 686 breast cancer patients. Patients took four 500-mg
      capsules of placebo or curcumin three times daily throughout their prescribed
      course of RT until 1 week post-RT. RESULTS: A total of 686 patients were included
      in the final analyses (87.5% white females, mean age = 58). Linear mixed-model
      analyses demonstrated that curcumin did not reduce radiation dermatitis severity
      at the end of RT compared to placebo (B (95% CI) = 0.044 (- 0.101, 0.188), p =
      0.552). Fewer curcumin patients with RDS > 3.0 suggested a trend toward reduced
      severity (7.4 vs. 12.9%, p = 0.082). Patient-reported changes in pain, symptoms,
      and quality of life were not statistically significant between arms. CONCLUSIONS:
      Oral curcumin did not significantly reduce radiation dermatitis severity compared
      to placebo. The skin rating variation and broad eligibility criteria could not
      account for the undetectable therapeutic effect. An objective measure for
      radiation dermatitis severity and further exploration for an effective treatment
      for radiation dermatitis is warranted.

PMID- 29192330
TI  - The role of ocelli in cockroach optomotor performance.
AB  - Insect ocelli are relatively simple eyes that have been assigned various
      functions not related to pictorial vision. In some species they function as
      sensors of ambient light intensity, from which information is relayed to various
      parts of the nervous system, e.g., for the control of circadian rhythms. In this
      work we have investigated the possibility that the ocellar light stimulation
      changes the properties of the optomotor performance of the cockroach Periplaneta
      americana. We used a virtual reality environment where a panoramic moving image
      is presented to the cockroach while its movements are recorded with a trackball.
      Previously we have shown that the optomotor reaction of the cockroach persists
      down to the intensity of moonless night sky, equivalent to less than 0.1
      photons/s being absorbed by each compound eye photoreceptor. By occluding the
      compound eyes, the ocelli, or both, we show that the ocellar stimulation can
      change the intensity dependence of the optomotor reaction, indicating involvement
      of the ocellar visual system in the information processing of movement. We also
      measured the cuticular transmission, which, although relatively large, is
      unlikely to contribute profoundly to ocellar function, but may be significant in
      determining the mean activity level of completely blinded cockroaches.

PMID- 29192331
TI  - Are neutrophil, platelet and eosinophil-to-lymphocyte ratio and red blood cell
      distribution width can be used for nasal polyposis?
AB  - INTRODUCTION: The aim of this study is to explore the relationship of neutrophil,
      platelet and eosinophil-to-lymphocyte ratios and red blood cell distribution
      width values with nasal polyposis, and whether this could be a predictive
      parameter that can be used for the severity and recurrence risk of the disease.
      METHOD: Neutrophil/lymphocyte, platelet/lymphocyte, eosinophil/lymphocyte ratios
      and red blood cell distribution width values were compared between nasal
      polyposis patients who were reviewed in a retrospective manner and the control
      group comparable for age and sex. Moreover, the nasal polyposis group was grouped
      for nasal polyposis severity and recurrence, and these subgroups were
      statistically compared, too. RESULTS: When the nasal polyposis patient group and
      the control group are compared, no statistically significant difference was found
      between two groups except for eosinophil/lymphocyte ratio. While only the
      difference between nasal polyposis severity and eosinophil/lymphocyte ratio is
      statistically significant, there was no parameter with statistically significant
      difference for recurrence. CONCLUSION: We think that caution should be exercised
      when using these new hematological parameters which can be affected by many
      factors for the presence, severity and recurrence risk of nasal polyposis, and
      literature data should be proven by conducting different and objective studies on
      this subject.

PMID- 29192332
TI  - Mosquito bites mimicking lesions on whole-body MRI for cancer staging in
      children.

PMID- 29192333
TI  - Individual benefits of enoxaparin treatment in branch vein occlusion.

PMID- 29192334
TI  - Putative Independent Evolutionary Reversals from Genotypic to Temperature
      Dependent Sex Determination are Associated with Accelerated Evolution of Sex
      Determining Genes in Turtles.
AB  - The evolutionary lability of sex-determining mechanisms across the tree of life
      is well recognized, yet the extent of molecular changes that accompany these
      repeated transitions remain obscure. Most turtles retain the ancestral
      temperature-dependent sex determination (TSD) from which multiple transitions to
      genotypic sex determination (GSD) occurred independently, and two contrasting
      hypotheses posit the existence or absence of reversals back to TSD. Here we
      examined the molecular evolution of the coding regions of a set of gene
      regulators involved in gonadal development in turtles and several other
      vertebrates. We found slower molecular evolution in turtles and crocodilians
      compared to other vertebrates, but an acceleration in Trionychia turtles and at
      some phylogenetic branches demarcating major taxonomic diversification events. Of
      all gene classes examined, hormone signaling genes, and Srd5a1 in particular,
      evolve faster in many lineages and especially in turtles. Our data show that sex
      linked genes do not follow a ubiquitous nor uniform pattern of molecular
      evolution. We then evaluated turtle nucleotide and protein evolution under two
      evolutionary hypotheses with or without GSD-to-TSD reversals, and found that when
      GSD-to-TSD reversals are considered, all transitional branches irrespective of
      direction, exhibit accelerated molecular evolution of nucleotide sequences, while
      GSD-to-TSD transitional branches also show acceleration in protein evolution.
      Significant changes in predicted secondary structure that may affect protein
      function were identified in three genes that exhibited hastened evolution in
      turtles compared to other vertebrates or in transitional versus non-transitional
      branches within turtles, rendering them candidates for a key role during SDM
      evolution in turtles.

PMID- 29192335
TI  - Diversity and Cyclical Seasonal Transitions in the Bacterial Community in a Large
      and Deep Perialpine Lake.
AB  - High-throughput sequencing (HTS) was used to analyze the seasonal variations in
      the bacterioplankton community composition (BCC) in the euphotic layer of a large
      and deep lake south of the Alps (Lake Garda). The BCC was analyzed throughout two
      annual cycles by monthly samplings using the amplification and sequencing of the
      V3-V4 hypervariable region of the 16S rRNA gene by the MiSeq Illumina platform.
      The dominant and most diverse bacterioplankton phyla were among the more
      frequently reported in freshwater ecosystems, including the Proteobacteria,
      Cyanobacteria, Bacteroidetes, Verrucomicrobia, Actinobacteria, and
      Planctomycetes. As a distinctive feature, the development of the BCC showed a
      cyclical temporal pattern in the two analyzed years and throughout the euphotic
      layer. The recurring temporal development was controlled by the strong
      seasonality in water temperature and thermal stratification, and by cyclical
      temporal changes in nutrients and, possibly, by the remarkable annual cyclical
      development of cyanobacteria and eukaryotic phytoplankton hosting
      bacterioplankton that characterizes Lake Garda. Further downstream analyses of
      operational taxonomic units associated to cyanobacteria allowed confirming the
      presence of the most abundant taxa previously identified by microscopy and/or
      phylogenetic analyses, as well as the presence of other small
      Synechococcales/Chroococcales and rare Nostocales never identified so far in the
      deep lakes south of the Alps. The implications of the high diversity and strong
      seasonality are relevant, opening perspectives for the definition of common and
      discriminating patterns characterizing the temporal and spatial distribution in
      the BCC, and for the application of the new sequencing technologies in the
      monitoring of water quality in large and deep lakes.

PMID- 29192336
TI  - Identification of opossums Didelphis aurita (Wied-Neuweid, 1826) as a definitive
      host of Sarcocystis falcatula-like sporocysts.
AB  - This study was conducted to identify the Sarcocystis species that infect the
      opossum Didelphis aurita in order to determine which sporocysts they are
      excreating in to the environment and help determine the role of D. aurita in the
      epidemiology of Sarcocystis. Sporocysts were obtained from intestinal tracts of 8
      of 13 D. aurita trapped in Rio de Janeiro state, Brazil, and were orally
      inoculated into Melopsittacus undulatus and Balb/c nude Mus musculus. Portions of
      organs and muscles were processed for histology, immunohistochemistry,
      transmission electron microscopy (TEM), and PCR using primers JNB 33/54, and ITS.
      Amplification products were subjected to RFLP using DraI and HinfI. Some birds
      were euthanized 6, 7, 13, 16, and 24 days after inoculation (DAI). All other
      birds and all mice were euthanized 60 DAI. Schizonts were observed in the lungs
      using histology and immunostaining in birds examined prior to 60 DAI. Sarcocysts
      with a ~ 1.5-MUm-thick wall were found in the breast, thigh, and tongue of some
      birds. Sarcocystis asexual stages were isolated in cell cultures inoculated with
      sporozoites. Parasite DNA isolated from bird tissues and cell cultures
      demonstrated that S. falcatula-like parasites were present in all samples derived
      from positive opossums. Asexual stages molecularly characterized as S. lindsayi
      like were isolated in cell culture from one opossum with an apparent multiple
      infection. This study demonstrated that D. aurita is a definitive host for S.
      falcatula-like parasites and indicates that S. lindsayi-like parasites can be
      found in coinfections of this opossum species.

PMID- 29192337
TI  - Pediatric emergency department visits for pedestrian and bicyclist injuries in
      the US.
AB  - BACKGROUND: Despite reductions in youth pedestrian and bicyclist deaths over the
      past two decades, these injuries remain a substantial cause of morbidity and
      mortality for children and adolescents. There is a need for additional
      information on non-fatal pediatric pedestrian injuries and the role of traumatic
      brain injury (TBI), a leading cause of acquired disability. METHODS: Using a
      multi-year national sample of emergency department (ED) records, we estimated
      annual motorized-vehicle related pediatric pedestrian and bicyclist (i.e.
      pedalcyclist) injury rates by age and region. We modeled in-hospital fatality
      risk controlling for age, gender, injury severity, TBI, and trauma center status.
      RESULTS: ED visits for pediatric pedestrian injuries declined 19.3% (95% CI 16.8,
      21.8) from 2006 to 2012, with the largest decreases in 5-to-9 year olds and 10-to
      14 year olds. Case fatality rates also declined 14.0%. There was no significant
      change in bicyclist injury rates. TBI was implicated in 6.7% (95% CI 6.3, 7.1) of
      all pedestrian and bicyclist injuries and 55.5% (95% CI 27.9, 83.1) of
      fatalities. Pedestrian ED visits were more likely to be fatal than bicyclist
      injuries (aOR = 2.4, 95% CI 2.3, 2.6), with significant additive interaction
      between pedestrian status and TBI. CONCLUSIONS: TBI in young pedestrian ED
      patients was associated with a higher risk of mortality compared to cyclists.
      There is a role for concurrent clinical focus on TBI recovery alongside ongoing
      efforts to mitigate and prevent motor vehicle crashes with pedestrians and
      bicyclists. Differences between youth pedestrian and cycling injury trends merit
      further exploration and localized analyses, with respect to behavior patterns and
      interventions. ED data captures a substantially larger number of pediatric
      pedestrian injuries compared to crash reports and can play a role in those
      analyses.

PMID- 29192338
TI  - Evolutionary trends in animal ribosomal DNA loci: introduction to a new online
      database.
AB  - Ribosomal DNA (rDNA) loci encoding 5S and 45S (18S-5.8S-28S) rRNAs are important
      components of eukaryotic chromosomes. Here, we set up the animal rDNA database
      containing cytogenetic information about these loci in 1343 animal species (264
      families) collected from 542 publications. The data are based on in situ
      hybridisation studies (both radioactive and fluorescent) carried out in major
      groups of vertebrates (fish, reptiles, amphibians, birds, and mammals) and
      invertebrates (mostly insects and mollusks). The database is accessible online at
      www.animalrdnadatabase.com . The median number of 45S and 5S sites was close to
      two per diploid chromosome set for both rDNAs despite large variation (1-74 for
      5S and 1-54 for 45S sites). No significant correlation between the number of 5S
      and 45S rDNA loci was observed, suggesting that their distribution and
      amplification across the chromosomes follow independent evolutionary
      trajectories. Each group, irrespective of taxonomic classification, contained
      rDNA sites at any chromosome location. However, the distal and pericentromeric
      positions were the most prevalent (> 75% karyotypes) for 45S loci, while the
      position of 5S loci was more variable. We also examined potential relationships
      between molecular attributes of rDNA (homogenisation and expression) and
      cytogenetic parameters such as rDNA positions, chromosome number, and morphology.

PMID- 29192339
TI  - Cytomixis in plants: facts and doubts.
AB  - The migration of nuclei between plant cells (cytomixis) is a mysterious cellular
      phenomenon frequently observable in the male meiosis of higher plants. Cytomixis
      attracts attention because of unknown cellular mechanisms underlying migration of
      nuclei and its potential evolutionary significance, since the genetic material is
      transferred between the cells that form pollen. Although cytomixis was discovered
      over a century ago, the advance in our understanding of this process has been
      rather insignificant because of methodological difficulties. The data that
      allowed for a new insight into this phenomenon were obtained by examining the
      migrating nuclei with electron and confocal laser microscopy, immunostaining, and
      fluorescence in situ hybridization. As has been shown, the chromatin migrating
      between cells is surrounded by an undamaged nuclear membrane. Such chromatin does
      not undergo heterochromatization and contains normal euchromatin markers. The
      condensation degree of the migrating chromatin corresponds to the current meiotic
      stage, and normal structures of synaptonemal complex are present in the migrating
      part of the nucleus. The cells involved in cytomixis lack any detectable
      morphological and molecular markers of programmed cell death. It has been shown
      that individual chromosomes and genomes (in the case of allopolyploids) have no
      predisposition to the migration between cells, i.e., parts of the nucleus are
      involved in cytomixis in a random manner. However, the fate of migrating
      chromatin after it has entered the recipient cell is still vague. A huge amount
      of indirect data suggests that migrating chromatin is incorporated into the
      nucleus of the recipient cell; nonetheless, the corresponding direct evidences
      are still absent. No specific markers of cytomictic chromatin have been yet
      discovered. Thus, the causes and consequences of cytomixis are still disputable.
      This review briefs the recent data on the relevant issues, describes the
      classical and modern methodological approaches to analysis of the intercellular
      migration of nuclei, and discusses the problems in cytomixis research and its
      prospects.

PMID- 29192340
TI  - The effect of polarized light on the organization of collagen secreted by
      fibroblasts.
AB  - Recent studies have demonstrated the beneficial effect of low-power lasers and
      polarized light on wound healing, inflammation, and the treatment of
      rheumatologic and neurologic disorders. The overall effect of laser irradiation
      treatment is still controversial due to the lack of studies on the biochemical
      mechanisms and the optimal parameters for the incident light that should be
      chosen for particular applications. Here, we study how NIH/3T3 fibroblasts
      respond to irradiation with linearly polarized light at different polarization
      angles. In particular, we examined vascular endothelial growth factor (VEGF)
      secretion, differentiation to myofibroblasts, and collagen organization in
      response to 800 nm polarized light at 0 degrees , 45 degrees , 90 degrees , and
      135 degrees  with a power density of 40 mW/cm2 for 6 min every day for 6 days.
      Additional experiments were conducted in which the polarization angle of the
      incident was changed every day to induce an isotropic distribution of collagen.
      The data presented here shows that polarized light can upregulate VEGF
      production, myofibroblast differentiation, and induce different collagen
      organization in response to different polarization angles of the incident beam.
      These results are encouraging and demonstrate possible methods for controlling
      cell response through the polarization angle of the laser light, which has
      potential for the treatment of wounds.

PMID- 29192341
TI  - Linking Time-Use Data to Explore Health Outcomes: Choosing to Vaccinate Against
      Influenza.
AB  - To inform public health and medical decision makers concerning vaccination
      interventions, a methodology for merging and analyzing detailed activity data and
      health outcomes is presented. The objective is to investigate relationships
      between individual's activity choices and their decision to receive an influenza
      vaccination. Data from the Behavioral Risk Factor Surveillance System (BRFSS) are
      used to predict vaccination rates in the American Time Use Survey (ATUS) data
      between 2003 and 2013 by using combined socioeconomic and demographic
      characteristics. The correlations between the extensive (do or not do) and
      intensive (how much) decisions to perform activities and influenza vaccination
      are further explored. Significant positive and negative correlations were found
      between several activities and vaccination. For some activities, the sign of the
      correlation flips when considering either the intensive or the extensive
      decision. This flip occurs with highly studied activities, like smoking.
      Correlations between activities and vaccination can provide an additional metric
      for targeting those least likely to vaccinate. The methodology outlined in this
      paper can be replicated to explore correlation among actions and other health
      outcomes.

PMID- 29192342
TI  - Zoonotic Enterobacterial Pathogens Detected in Wild Chimpanzees.
AB  - Infectious diseases including those acquired through direct or indirect contact
      with people and livestock threaten the survival of wild great apes. Few studies
      have reported enterobacterial pathogens in chimpanzees. We used multiplex PCR to
      screen faeces of chimpanzees sharing a landscape with villagers and livestock in
      Bulindi, Uganda for Salmonella spp., enterohemorrhagic Escherichia coli (E. coli)
      and Shigella spp./enteroinvasive E. coli. All three potentially zoonotic
      pathogens were detected. Individual prevalence ranged between 7 and 20%, with
      most infections observed in mature male chimpanzees. These preliminary findings
      suggest detailed investigation of enterobacterial infections in people, primates
      and livestock in this ecosystem is warranted.

PMID- 29192343
TI  - A View on the Importance of "Multi-Attribute Method" for Measuring Purity of
      Biopharmaceuticals and Improving Overall Control Strategy.
AB  - Today, we are experiencing unprecedented growth and innovation within the
      pharmaceutical industry. Established protein therapeutic modalities, such as
      recombinant human proteins, monoclonal antibodies (mAbs), and fusion proteins,
      are being used to treat previously unmet medical needs. Novel therapies such as
      bispecific T cell engagers (BiTEs), chimeric antigen T cell receptors (CARTs),
      siRNA, and gene therapies are paving the path towards increasingly personalized
      medicine. This advancement of new indications and therapeutic modalities is
      paralleled by development of new analytical technologies and methods that provide
      enhanced information content in a more efficient manner. Recently, a liquid
      chromatography-mass spectrometry (LC-MS) multi-attribute method (MAM) has been
      developed and designed for improved simultaneous detection, identification,
      quantitation, and quality control (monitoring) of molecular attributes (Rogers et
      al. MAbs 7(5):881-90, 2015). Based on peptide mapping principles, this powerful
      tool represents a true advancement in testing methodology that can be utilized
      not only during product characterization, formulation development, stability
      testing, and development of the manufacturing process, but also as a platform
      quality control method in dispositioning clinical materials for both innovative
      biotherapeutics and biosimilars.

PMID- 29192344
TI  - Pulseless supracondylar humeral fractures in children: vascular complications in
      a ten year series.
AB  - PURPOSE: The management of pulseless supracondylar fractures remains
      controversial. The aims of this study were to: (1) analyse functional and
      vascular outcomes of conservative treatment for cases with absent pulse before
      reduction, whether patients showed limb ischaemia or not; and (2) identify
      factors associated with vascular complications. METHODS: Twenty-seven children
      with absent pulses on presentation were treated consecutively between 1999 and
      2009. The brachial artery was surgically explored in cases of persistent signs of
      ischaemia after reduction. Signs of vascular impairment were recorded in the
      early post-operative period and at a mean final follow-up of 3.5 years. RESULTS:
      Recurrent ischaemia with a compartment syndrome occurred in a patient with
      initial ischaemia and a pink, pulseless hand after reduction. Patients with an
      initially well-perfused hand and those with pre-operative ischaemia and palpable
      pulses after reduction had satisfactory outcomes, as did patients with early
      arterial exploration. No patient showed signs of chronic vascular impairment. The
      need for vascular repair was significantly correlated with open fracture, initial
      ischaemia and nerve impairment. CONCLUSIONS: Conservative management of
      supracondylar fractures with absent pulses avoided long-term vascular
      complications provided that patients with a pulseless, well-perfused hand on
      presentation were closely monitored after reduction. Further study is necessary
      to determine whether a forearm Doppler would help identify children with absent
      pulses after reduction who need surgical revascularisation due to an insufficient
      collateral circulation.

PMID- 29192345
TI  - Transporter-Mediated Interaction Between Platinum Drugs and Sorafenib at the
      Cellular Level.
AB  - Combining the multikinase inhibitor sorafenib with the platinum-based
      chemotherapy of solid tumors was expected to improve treatment outcome. However,
      in many clinical trials, no benefit from sorafenib addition to the platinum
      containing regimen could be demonstrated. Moreover, in some studies, decreased
      survival of ovarian cancer patients as well as non-small cell lung cancer
      patients with squamous cell histology was observed. The aim of this study was to
      investigate the cellular mechanisms of the pharmacological interaction between
      platinum drugs and sorafenib in different cancer cell lines. The interaction was
      characterized by combination index analysis, platinum accumulation and DNA
      platination were determined using flameless atomic absorption spectrometry, and
      protein expression was assessed with Western blot. In the sensitive A2780 ovarian
      carcinoma and H520 squamous cell lung carcinoma cell lines, sorafenib induced
      downregulation of Na+,K+-ATPase. In A2780 cells, the kinase inhibitor also
      decreased the expression of copper transporter 1 (CTR1). As a result, sorafenib
      treatment led to a diminished cellular accumulation of cisplatin and carboplatin
      and to a decrease in DNA platination in these cell lines. This was not the case
      in the cisplatin-resistant A2780cis ovarian carcinoma and H522 lung
      adenocarcinoma cell lines featuring lower basal expression of the above-mentioned
      transporters. In all cell lines studied, an antagonistic interaction between
      platinum drugs and sorafenib was found. Our results suggest that sorafenib
      impairs cisplatin and carboplatin uptake through downregulation of CTR1 and/or
      Na+,K+-ATPase resulting in reduction of DNA platination. This effect is not
      observed in cancer cells with defects in platinum accumulation.

PMID- 29192346
TI  - In Vitro Sonothrombolysis Enhancement by Transiently Stable Microbubbles Produced
      by a Flow-Focusing Microfluidic Device.
AB  - Therapeutic approaches that enhance thrombolysis by combining recombinant tissue
      plasminogen activator (rtPA), ultrasound, and/or microbubbles (MBs) are known as
      sonothrombolysis techniques. To date, sonothrombolysis approaches have primarily
      utilized commercially available MB formulations (or derivatives thereof) with
      diameters in the range 1-4 um and circulation lifetimes between 5 and 15 min. The
      present study evaluated the in vitro sonothrombolysis efficacy of large diameter
      MBs (d MB >= 10 um) with much shorter lifetimes that were produced on demand and
      in close proximity to the blood clot using a flow-focusing microfluidic device.
      MBs with a N2 gas core and a non-crosslinked bovine serum albumin shell were
      produced with diameters between 10 and 20 um at rates between 50 and 950 * 103
      per second. Use of these large MBs resulted in approximately 4.0-8.8 fold
      increases in thrombolysis rates compared to a clinical rtPA dose and
      approximately 2.1-4.2 fold increases in thrombolysis rates compared to
      sonothrombolysis techniques using conventional MBs. The results of this study
      indicate that the large diameter microbubbles with transient stability are
      capable of significantly enhanced in vitro sonothrombolysis rates when delivered
      directly to the clot immediately following production by a flow focusing
      microfluidic device placed essentially in situ adjacent to the clot.

PMID- 29192347
TI  - Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia:
      prospects for clinical application of NUDT15 genotyping.
AB  - The thiopurine drugs 6-mercaptopurine (6-MP) and azathiopurine (AZA) are widely
      used to treat inflammatory bowel disease. However, the incidence of adverse
      reactions is high, particularly in Asia, and the mechanisms of toxicity in Asian
      populations remain unclear. Thiopurine S-methyltransferase (TPMT) is a well-known
      enzyme that inactivates AZA or 6-MP through methylation and is one of the few
      pharmacogenetic predictors used in clinical settings in Western countries.
      Individuals carrying TPMT-deficient genetic variants require reduced drug doses,
      but this treatment modification is are not applicable to East Asian populations.
      Several genes code thiopurine-metabolizing enzymes, including TPMT, multidrug
      resistance protein 4, and inosine triphosphatase. These genes have been studied
      as candidate pharmacogenetic markers; however, it remains unclear why Asian
      populations seem to be more intolerant than other ethnic groups to a full dose of
      thiopurines. A genome-wide association approach to identify Asian-specific
      pharmacogenetic markers in Korean patients with Crohn's disease revealed that a
      non-synonymous single nucelotide polymorphism in nucleoside diphosphate-linked
      moiety X-type motif 15 (NUDT15) which causes p.Arg139Cys was strongly associated
      with thiopurine-induced early leukopenia. Six common haplotypes of NUDT15 were
      reported, and five variants showed medium-to-low enzyme activities, compared with
      the wild haplotype. NUDT15 hydrolyzes the thiopurine active metabolites 6-thio
      GTP and 6-thio-dGTP; variants of NUDT15 had lower enzyme activities, causing
      higher levels of thiopurine active metabolites, resulting in thiopurine-induced
      leukopenia. In clinical application, NUDT15 genotyping is a good candidate for
      predicting thiopurine toxicity in East Asian populations. However, the
      association of NUDT15 diplotypes with thiopurine toxicity remains unclear.
      Further analyses with large cohorts to confirm the clinical effects of each
      haplotype are planned.

PMID- 29192348
TI  - A nationwide population-based study of common bile duct stone recurrence after
      endoscopic stone removal in Korea.
AB  - BACKGROUND: There is no consensus whether patients who underwent endoscopic
      common bile duct (CBD) stone removal should be followed up periodically and
      whether patients with gallbladder (GB) stones should undergo cholecystectomy.
      Thus, this study aimed to investigate the recurrence rate of CBD stones and the
      difference in recurrence rate according to cholecystectomy. METHODS: We conducted
      a population-based study using the National Health Insurance database. Patients
      diagnosed with CBD stones and with procedure registry of endoscopic stone removal
      were included. The primary outcome was the recurrence rate of CBD stones. The
      secondary outcome was the difference in recurrence rate of CBD stones according
      to cholecystectomy. RESULTS: A total of 46,181 patients were identified. The mean
      follow-up was 4.2 years. The first CBD stone recurrence occurred in 5228 (11.3%)
      patients. The cumulative first recurrence rate was low. However, the second and
      third recurrence rates were 23.4 and 33.4%, respectively. The cumulative second
      and third recurrence rates were high and gradually increased with time. The
      recurrence rate in the non-cholecystectomy group was higher than that in the
      cholecystectomy group (p < 0.0001). The relative risk for CBD stone recurrence in
      the non-cholecystectomy group was higher in younger patients, with 3.198 in
      patients < 50 years, 2.371 in 50-59 years, 1.618 in 60-69 years, and 1.262 in >=
      70 years (p < 0.0001). CONCLUSIONS: Regular follow-up is not routinely
      recommended for patients with first-time endoscopic stone removal, but is
      recommended for patients with recurrent stones. Cholecystectomy is recommended
      for patients with GB stones who are younger than 70 years.

PMID- 29192349
TI  - Placement of an antibiotic oral pack on the hard palate after primary cleft
      palatoplasty: a randomized controlled trial into the effect on fistula rates.
AB  - OBJECTIVE: The objective of this study is to determine whether placement of an
      antibiotic oral pack on the hard palate reduces fistula rates after primary cleft
      palatoplasty. SUBJECTS AND METHODS: This study was a parallel blocked randomized
      controlled trial. The study consisted of two groups of 100 patients each with non
      syndromic unilateral complete cleft lip, alveolus, and hard and soft palate that
      underwent primary palatoplasty. Group A had an oral pack placed on the hard
      palate for 5 days postoperatively while group B did not. Occurrence of fistulae
      between both groups was tested using odds ratios (OR). RESULTS: In 2% of the
      patients in group A, a fistula was found 6 months after palatal surgery. In
      contrast, in 21% of the patients in group B, a palatal fistula could be
      confirmed. The fistula occurrence in group A was statistically significantly
      lower than that in group B (OR = 0.0768, CI = [0.02 ... 0.34], p < 0.001).
      CONCLUSION: The findings of this study provide evidence that the rate of fistula
      formation after primary palatoplasty is significantly reduced if a pack soaked
      with antibiotic cream is placed on the palate postoperatively for 5 days.
      CLINICAL RELEVANCE: The use of an antibiotic pack after cleft palate repair can
      be recommended to prevent occurrence of oronasal fistulae.

PMID- 29192351
TI  - The implication of probiotics in the prevention of dental caries.
AB  - The current oral health crisis, whose causes are varied and complex, necessitates
      timely oral evaluation and early detection and treatment of oral health problems.
      Dramatic changes in eating habits and lifestyles are associated with the recent
      decline in oral health. Probiotics are "good" bacteria that support digestion and
      a healthy immune system and offer various health benefits to the host.
      Traditionally, probiotics have been used to improve gut health; the most common
      uses have historically been as a treatment or prevention of gastrointestinal
      infections and disease. During the last decade, studies have additionally
      suggested the intake of probiotics for oral health purposes. Probiotic use
      provides an effective strategy to combat oral disease, including the development
      of dental caries and periodontal infection. The aim of this review is to describe
      the beneficial roles of probiotic bacteria in the oral cavity and the potential
      mechanisms by which these bacteria exert their effects on oral health.

PMID- 29192350
TI  - Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis.
AB  - PURPOSE: Many studies suggest a role for cholesterol in cancer development. Serum
      cholesterol levels have been observed to be low in newly diagnosed lymphoma
      cases. The objective of these analyses was to examine the time-varying
      relationship of cholesterol with lymphomagenesis in the 10 years prior to
      diagnosis by lymphoma subtype. METHODS: Participants were selected from the
      combined membership of six National Cancer Institute-funded Cancer Research
      Network health plans from 1998 to 2008, excluding members with human
      immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident
      lymphoma cases within this population were ascertained and matched with up to
      five controls. Total serum cholesterol, high-density lipoprotein, and low-density
      lipoprotein were collected from plan databases. Multilevel, multivariable
      longitudinal models were fit after choosing the best polynomial order by deviance
      statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol
      trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined
      (n = 12,635) as well as six subtypes of the latter. RESULTS: For all categories,
      lymphoma cases had statistically significantly lower estimated total serum
      cholesterol, high-density lipoprotein, and low-density lipoprotein levels than
      controls in the years prior to diagnosis/index date. Between-group differences
      were most pronounced 3-4 years prior to diagnosis, when cases' cholesterol levels
      declined steeply. CONCLUSIONS: This analysis is the first to examine changes in
      serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol
      levels was evident several years before diagnosis. Our results suggest that
      cholesterol-related pathways have an important relationship with lymphomagenesis
      and low cholesterol could be a preclinical lymphoma marker.

PMID- 29192352
TI  - Peer Victimization and Adjustment in Young Adulthood: Commentary on the Special
      Section.

PMID- 29192353
TI  - Effects of a mobility monitoring system on the cost of care in relation to
      reimbursement at Swiss nursing homes: learnings from a randomized controlled
      trial.
AB  - BACKGROUND/OBJECTIVE: Nursing homes in Switzerland are under pressure to
      efficiently coordinate staff activities to cover their personnel costs under the
      care financing system. In this study, the use of a mobility monitoring system
      accompanied with case conferences was investigated in order to improve sleep
      quality and estimate the cost benefit of this intervention. METHOD: In an open
      two-phase randomized controlled trial at three nursing homes, residents with
      cognitive impairment were randomly assigned to an intervention group and a
      control group. In the intervention group, a 10-week period of intensive use of
      the monitoring system and case conferences led by an advanced nurse practitioner
      (Phase I) was followed by 3 months of reduced use of the monitoring system and
      case conferences led by an internal registered nurse (Phase II). In the control
      group, the monitoring system was only used for data acquisition. Nurses reported
      the activities with a specifically developed tool. Based on the recorded
      activities, the cost of care was calculated. The correlating reimbursement per
      patient was calculated from the care levels in the Swiss reimbursement system.
      Data from 44 residents was included in the analysis with a linear mixed model.
      RESULTS: Although analysis revealed no statistically significant effects, results
      indicate that the use of a monitoring system can guide nurses in organizing their
      tasks to increase effectiveness. Information systems such as the mobility monitor
      can help to identify single outliers that do not correspond with the overall
      situation. CONCLUSION: In the health care system, problematic individual cases
      can account for a disproportionally high cost levels. It was shown that
      information systems can have a significant economic impact in the long run. TRIAL
      REGISTRATION: The study is registered at the German Clinical Trials Register
      under the Nr. DRKS-ID: DRKS00006829 .

PMID- 29192354
TI  - Prognostic Implication of Inflammation-based Prognostic Scores in Patients with
      Intrahepatic Cholangiocarcinoma Treated with First-line Gemcitabine plus
      Cisplatin.
AB  - Background We aimed to comprehensively evaluate the prognostic value of
      inflammation-based prognostic scores, including the modified Glasgow Prognostic
      Score (mGPS), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio
      (PLR), exclusively in patients with advanced intrahepatic cholangiocarcinoma
      (iCCA). Methods Between May 2010 and April 2015, 305 patients with histologically
      documented unresectable or metastatic iCCA were treated with first-line
      gemcitabine plus cisplatin (GemCis). Among these, 257 patients had complete data
      for inflammation-based prognostic scores and were included. Results Median age
      was 59 (range: 27-78) years, and 158 patients (61.5%) were males. High mGPS was
      independently associated with poor progression-free survival (PFS; mGPS >=1 vs.
      0: median, 3.9 vs. 5.5 months; P = 0.001) and overall survival (OS; mGPS >=1 vs.
      0; median, 6.9 vs. 14.1 months; P = 0.002) in the multivariate analysis.
      Regarding high NLR (> median) and PLR (> median), although a potential
      association existed with poor PFS or OS in the univariate analysis, these did not
      remain as significant in the multivariate analyses. Conclusion The current study
      suggests that mGPS might be the relevant prognostic index that could stratify the
      survival outcomes of patients with unresectable or metastatic iCCA who received
      first-line GemCis.

PMID- 29192356
TI  - Measuring 3D shape in orthodontics through geometric morphometrics.
AB  - BACKGROUND: Geometric morphometrics (GMM) has been traditionally applied to the
      field of biology to study developmental differentiations between species.
      Orthodontics deals with the shape and size of the face and its components. While
      several tools have been used to measure size, proportions, and relations between
      anatomical components, shape has been mainly described by esthetic criteria. The
      purpose of this paper is to present methods to measure shape of 3D orthodontic
      data, beyond the conventional tools that have been traditionally used in
      cephalometrics and in facial and dental cast analysis. FINDINGS: The authors
      showcase an example of applying geometric morphometrics to measure palates from
      scanned dental casts. GMM can be used as a useful tool to describe the three
      dimensional shape of surfaces of orthodontic interest. A general introduction to
      the theoretical principles of how to apply GMM is provided. CONCLUSIONS:
      Variability can be measured through the Principal Component Analysis (PCA) and
      can lead to the identification of shape patterns and sources of variability of
      the shape, independently from changes in size.

PMID- 29192355
TI  - Venous occlusion plethysmography vs. Doppler ultrasound in the assessment of leg
      blood flow kinetics during different intensities of calf exercise.
AB  - PURPOSE: It has recently been shown that venous occlusion plethysmography (VOP)
      can successfully assess the rate of increase in leg blood flow (LBF) (LBF
      kinetics) responses during calf exercise, but there is lack of data supporting
      its validity. METHODS: Using Doppler ultrasound (DU) as a criterion standard
      technique, we tested the hypothesis that VOP would provide similar estimates of
      LBF kinetics responses as DU during calf plantar-flexion exercise at a range of
      different intensities. Ten healthy men performed repeated intermittent calf
      plantar-flexion contractions (3 s duty cycles, 1 s contraction/2 s relaxation) at
      30, 50 and 70% maximum voluntary contraction (MVC) on different days. RESULTS:
      Resting LBF values were significantly (P < 0.05) larger for DU than VOP but the
      overall mean LBF responses during exercise were not different (P > 0.05) between
      DU and VOP (30% MVC: 330 +/- 78 vs. 313 +/- 92 ml/min; 50% MVC: 515 +/- 145 vs.
      483 +/- 164 ml/min; 70% MVC: 733 +/- 218 vs. 616 +/- 229 ml/min). LBF kinetics
      analyses revealed that the end-amplitude at the highest intensity (70% MVC) was
      significantly higher when measured by DU compared with VOP, but all other
      kinetics parameters were not different between VOP and DU. CONCLUSIONS: Given
      that these slight differences in amplitude observed during exercise can be
      explained by differences in vascular regions which the two techniques assess, our
      results suggest that VOP can accurately assess LBF kinetics responses during calf
      plantar-flexion exercise at intensities between 30 and 70% MVC.

PMID- 29192357
TI  - Three new species of Paraboea (Gesneriaceae) from limestone karsts of China based
      on morphological and molecular evidence.
AB  - BACKGROUND: The limestone karsts of Southeast Asia and South China are a major
      biodiversity hotspot of global terrestrial biomes. With more than 130 described
      species, Paraboea has become one of the most characteristic plant groups in the
      Southeast Asian limestone flora. During the course of extensive field work on the
      limestone formations of southern and southwestern China, three unknown species of
      Paraboea were collected. RESULTS: Molecular phylogenetic analyses based on
      nuclear ITS and chloroplast trnL-F sequences strongly confirm the placements of
      the three new species in Paraboea sensu Puglisi et al. (Taxon 65:277-292.
      https://doi.org/10.12705/652.5 , 2016). Moreover, these three novelties can be
      distinguished from known Paraboea species with distinct morphological characters,
      further supporting their recognition as new species. CONCLUSIONS: With the
      support of detailed morphological studies and molecular phylogenetic analyses,
      Paraboea dushanensis, P. sinovietnamica and P. xiangguiensis are recognized as
      three species new to science.

PMID- 29192358
TI  - Cryopreservation of male and female gonial cells by vitrification in the
      critically endangered cyprinid honmoroko Gnathopogon caerulescens.
AB  - We investigated the feasibility of cryopreservation of spermatogonia and oogonia
      in the critically endangered cyprinid honmoroko Gnathopogon caerulescens using
      slow-cooling (freezing) and rapid-cooling (vitrification) methods. Initially, we
      examined the testicular cell toxicities and glass-forming properties of the five
      cryoprotectants: ethylene glycol (EG), glycerol (GC), dimethyl sulfoxide (DMSO),
      propylene glycol (PG), and 1,3-butylene glycol (BG), and we determined
      cryoprotectant concentrations that are suitable for freezing and vitrification
      solutions, respectively. Subsequently, we prepared the freezing solutions of EG,
      GC, DMSO, PG, and BG at 3, 2, 3, 2, and 2 M and vitrification solutions at 7, 6,
      5, 5, and 4 M, respectively. Following the cryopreservation of the testicular
      cells mainly containing early-stage spermatogenic cells (e.g., spermatogonia and
      primary spermatocytes), cells were cultured for 7 days and immunochemically
      stained against germ cell marker protein Vasa. Areas occupied by Vasa-positive
      cells indicated that vitrification led to better survival of germ cells than the
      freezing method, and the best result was obtained with 5 M PG, about 50% recovery
      of germ cells following vitrification. In the case of ovarian cells containing
      oogonia and stage I, II, and IIIa oocytes, vitrification with 5 M DMSO resulted
      the best survival of oogonia, with equivalent cell numbers to those cultured
      without vitrification. The present data suggest that male and female gonial cells
      of the endangered species G. caerulescens can be efficiently cryopreserved using
      suitable cryoprotectants for spermatogonia and oogonia, respectively.

PMID- 29192359
TI  - A field and laboratory study of the responses of cytoprotection and
      osmoregulation to salinity stress in mosquitofish (Gambusia affinis).
AB  - The mosquitofish (Gambusia affinis) naturally inhabits freshwater (FW; 1-30/00)
      and seawater (SW; 28-330/00) ponds in constructed wetland. To explore the
      physiological status and molecular mechanisms for salinity adaptation of the
      mosquitofish, cytoprotective responses and osmoregulation were examined. In the
      field study, activation of protein quality control (PQC) mechanism through
      upregulation of the abundance of heat shock protein (HSP) 90 and 70 and ubiquitin
      conjugated proteins was found in the mosquitofish gills from SW pond compared to
      the individuals of FW pond. The levels of aggregated proteins in mosquitofish
      gills had no significant difference between FW and SW ponds. Furthermore, the
      osmoregulatory responses revealed that the body fluid osmolality and muscle water
      contents of the mosquitofish from two ponds were maintained within a
      physiological range while branchial Na+/K+-ATPase (NKA) expression was higher in
      the individuals from SW than FW ponds. Subsequently, to further clarify whether
      the cellular stress responses and osmoregulation were mainly induced by
      hypertonicity, a laboratory salinity acclimation experiment was conducted. The
      results from the laboratory experiment were similar to the field study. Branchial
      PQC as well as NKA responses were induced by SW acclimation compared to FW
      acclimated individuals. Taken together, induction of gill PQC and NKA responses
      implied that SW represents an osmotic stress for mosquitofish. Activation of PQC
      was suggested to provide an osmoprotection to prevent the accumulation of
      aggregated proteins. Moreover, an increase in branchial NKA responses for
      osmoregulatory adjustment was required for the physiological homeostasis of body
      fluid osmolality and muscle water content.

PMID- 29192361
TI  - The Impact of Spiritual Intelligence, Gender and Educational Background on Mental
      Health Among College Students.
AB  - The present study is conducted on 300 PG-level college students in Haridwar,
      Uttarakhand (India). The aim of the present study is to examine the level of
      spiritual intelligence and mental health, to observe relationship between these
      two variables and also to identify the difference in spiritual intelligence and
      mental health across gender and educational background (arts and science). The
      purposive sampling technique is used to select 300 college students of both
      disciplines of arts and science from the four different government degree
      colleges/campuses in Haridwar. Integrated Spiritual Intelligence Scale and
      Mithila Mental Health Status Inventory are used to observe the level of these
      variables among college students. In the present study, correlational design is
      employed. All the statistical analyses are done with the help of computer
      software SPSS. To observe relationship Pearson correlation and to identify the
      difference t test are used. Findings of the study revealed that spiritual
      intelligence and mental health relate significantly among arts students, and male
      and female arts students separately have significant relationship between
      spiritual intelligence and mental health. Spiritual intelligence and mental
      health relate significantly among science students, and male and female science
      students separately have significant relationship between spiritual intelligence
      and mental health. No significant difference is found between male and female
      students in terms of spiritual intelligence. No significant difference is found
      between arts and science students in terms of spiritual intelligence. No
      significant difference is found between male and female students in terms of
      mental health. No significant difference is found between arts and science
      students in terms of mental health.

PMID- 29192362
TI  - The Ninth International Conference on Mycorrhiza in Prague: across mycorrhizal
      symbioses from molecules to global scales.

PMID- 29192360
TI  - Hyperglycemia-induced cardiac contractile dysfunction in the diabetic heart.
AB  - The development of a diabetic cardiomyopathy is a multifactorial process, and
      evidence is accumulating that defects in intracellular free calcium concentration
      [Ca2+]i or its homeostasis are related to impaired mechanical performance of the
      diabetic heart leading to a reduction in contractile dysfunction. Defects in
      ryanodine receptor, reduced activity of the sarcoplasmic reticulum calcium pump
      (SERCA) and, along with reduced activity of the sodium-calcium exchanger (NCX)
      and alterations in myofilament, collectively cause a calcium imbalance within the
      diabetic cardiomyocytes. This in turn is characterized by cytosolic calcium
      overloading or elevated diastolic calcium leading to heart failure. Numerous
      studies have been performed to identify the cellular, subcellular, and molecular
      derangements in diabetes-induced cardiomyopathy (DCM), but the precise
      mechanism(s) is still unknown. This review focuses on the mechanism behind DCM,
      the onset of contractile dysfunction, and the associated changes with special
      emphasis on hyperglycemia, mitochondrial dysfunction in the diabetic heart.
      Further, management strategies, including treatment and emerging therapeutic
      modalities, are discussed.

PMID- 29192363
TI  - Quantitative and Visual Assessments toward Potential Sub-mSv or Ultrafast FDG PET
      Using High-Sensitivity TOF PET in PET/MRI.
AB  - PURPOSE: Newer high-performance time-of-flight (TOF) positron emission tomography
      (PET) systems have the capability to preserve diagnostic image quality with low
      count density, while maintaining a high raw photon detection sensitivity that
      would allow for a reduction in injected dose or rapid data acquisition. To assess
      this, we performed quantitative and visual assessments of the PET images acquired
      using a highly sensitive (23.3 cps/kBq) large field of view (25-cm axial) silicon
      photomultiplier (SiPM)-based TOF PET (400-ps timing resolution) integrated with 3
      T-MRI in comparison to PET images acquired on non-TOF PET/x-ray computed
      tomography (CT) systems. PROCEDURES: Whole-body 2-deoxy-2-[18F]fluoro-D-glucose
      ([18F]FDG) PET/CT was acquired for 15 patients followed by whole body
      PET/magnetic resonance imaging (MRI) with an average injected dose of 325 +/- 84
      MBq. The PET list mode data from PET/MRI were reconstructed using full datasets
      (4 min/bed) and reduced datasets (2, 1, 0.5, and 0.25 min/bed). Qualitative
      assessment between PET/CT and PET/MR images were made. A Likert-type scale
      between 1 and 5, 1 for non-diagnostic, 3 equivalent to PET/CT, and 5 superior
      quality, was used. Maximum and mean standardized uptake values (SUVmax and
      SUVmean) of normal tissues and lesions detected were measured and compared.
      RESULTS: Mean visual assessment scores were 3.54 +/- 0.32, 3.62 +/- 0.38, and
      3.69 +/- 0.35 for the brain and 3.05 +/- 0.49, 3.71 +/- 0.45, and 4.14 +/- 0.44
      for the whole-body maximum intensity projections (MIPs) for 1, 2, and 4 min/bed
      PET/MR images, respectively. The SUVmean values for normal tissues were lower and
      statistically significant for images acquired at 4, 2, 1, 0.5, and 0.25 min/bed
      on the PET/MR, with values of - 18 +/- 28 % (p < 0.001), - 16 +/- 29 % (p =
      0.001), - 16 +/- 31 % (p = 0.002), - 14 +/- 35 % (p < 0.001), and - 13 +/- 34 %
      (p = 0.002), respectively. SUVmax and SUVpeak values of all lesions were higher
      and statistically significant (p < 0.05) for 4, 2, 1, 0.50, and 0.25 min/bed
      PET/MR datasets. CONCLUSION: High-sensitivity TOF PET showed comparable but still
      better visual image quality even at a much reduced activity in comparison to
      lower-sensitivity non-TOF PET. Our data translates to a seven times reduction in
      either injection dose for the same time or total scan time for the same injected
      dose. This "ultra-sensitivity" PET system provides a path to clinically
      acceptable extremely low-dose FDG PET studies (e.g., sub 1 mCi injection or sub
      mSv effective dose) or PET studies as short as 1 min/bed (e.g., 6 min of total
      scan time) to cover whole body without compromising diagnostic performance.

PMID- 29192364
TI  - Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter,
      retrospective analysis.
AB  - AIM: During our daily clinical practice using 11C-Choline PET/CT for restaging
      patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but
      significant occurrence of hypodense hepatic lesions with a different tracer
      uptake. Thus, we decided to evaluate the possible correlation between rPCa and
      these lesions as possible hepatic metastases. MATERIALS AND METHODS: We
      retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse
      after a radical treatment (surgery and/or radiotherapy). Among these, patients
      with a second tumor or other benign hepatic diseases were excluded. All patients
      underwent 11C-Choline PET/CT during the standard restaging workup of their
      disease. We analyzed CT images to evaluate the presence of hypodense lesions and
      PET images to identify the relative tracer uptake. In accordance to the
      subsequent oncological history, five clinical scenarios were recognized [Table
      1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence
      of previously unknown hepatic round hypodense areas at ldCT with normal rim
      uptake (Group B); evidence of previously known hepatic round hypodense areas at
      ldCT stable over time and with normal rim uptake (Group C); evidence of
      previously known hepatic round hypodense areas at ldCT, in a previous PET/CT
      scan, with or without rim uptake and significantly changing over time in terms of
      size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT
      with or without rim uptake confirmed as prostate liver metastases by
      histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical
      evaluation (Group E). We evaluated the correlation with PSA level at time of
      scan, rim SUVmax and association with local relapse or non-hepatic metastases
      (lymph nodes, bone, other parenchyma). RESULTS: Five hundred and forty-two
      consecutive patients were retrospectively enrolled. In 140 of the 542 patients
      more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline
      PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a
      normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%)
      belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and
      18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for
      Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A,
      7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence
      of positive findings at 11C-Choline PET/CT in any further anatomical area (local
      relapse, lymph node, bone, other extra hepatic sites) correlated with an higher
      PSA (p = 0.0285). In both the univariate and multivariate binary logistic
      regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were
      not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a
      significant correlation was found between the presence of liver metG (group D-E)
      and bone lesions (p= 0.00193). CONCLUSION: Our results indicate that liver
      metastases in relapsing prostate cancer may occur frequently. The real incidence
      evaluation needs more investigations. In this case and despite technical
      limitations, Choline PET/CT shows alterations of tracer distribution within the
      liver that could eventually be mistaken for simple cysts but can be suspected
      when associated to high trigger PSA, concomitant bone lesions or modification
      over time. In this clinical setting an accurate analysis of liver tracer
      distribution (increased or decreased uptake) by the nuclear medicine physician
      is, therefore, mandatory.

PMID- 29192365
TI  - EANM/EARL FDG-PET/CT accreditation - summary results from the first 200
      accredited imaging systems.
AB  - PURPOSE: From 2010 until July 2016, the EANM Research Ltd. (EARL) FDG-PET/CT
      accreditation program has collected over 2500 phantom datasets from approximately
      200 systems and 150 imaging sites worldwide. The objective of this study is to
      report the findings and impact of the accreditation program on the participating
      PET/CT systems. METHODS: To obtain and maintain EARL accredited status, sites
      were required to complete and submit two phantom scans - calibration quality
      control (CalQC), using a uniform cylindrical phantom and image quality control
      (IQQC), using a NEMA NU2-2007 body phantom. Average volumetric SUV bias and SUV
      recovery coefficients (RC) were calculated and the data evaluated on the basis of
      quality control (QC) type, approval status, PET/CT system manufacturer and
      submission order. RESULTS: SUV bias in 5% (n = 96) of all CalQC submissions (n =
      1816) exceeded 10%. After corrective actions following EARL feedback, sites
      achieved 100% compliance within EARL specifications. 30% (n = 1381) of SUVmean
      and 23% (n = 1095) of SUVmax sphere recoveries from IQQC submissions failed to
      meet EARL accreditation criteria while after accreditation, failure rate
      decreased to 12% (n = 360) and 9% (n = 254), respectively. Most systems
      demonstrated longitudinal SUV bias reproducibility within +/-5%, while RC values
      remained stable and generally within +/-10% for the four largest and +/-20% for
      the two smallest spheres. CONCLUSIONS: Regardless of manufacturer or model, all
      investigated systems are able to comply with the EARL specifications. Within the
      EARL accreditation program, gross PET/CT calibration errors are successfully
      identified and longitudinal variability in PET/CT performances reduced. The
      program demonstrates that a harmonising accreditation procedure is feasible and
      achievable.

PMID- 29192367
TI  - Intermedin1-53 Protects Cardiac Fibroblasts by Inhibiting NLRP3 Inflammasome
      Activation During Sepsis.
AB  - Sepsis is a disease that occurs as a result of systemic inflammatory response
      syndrome (SIRS) in response to an infection, contributing to multiple organ
      dysfunction and a high mortality rate. Interleukin-lbeta (IL-1beta) is a cytokine
      that plays critical roles in inflammation and cardiac dysfunction during severe
      sepsis. Intermedin1-53 (IMD1-53) has been recently discovered to possess
      potential endogenous anti-inflammatory and strong cardiovascular protective
      effects. To investigate whether IMD1-53 can inhibit the NLRP3/caspase-1/IL-1beta
      pathway to alleviate cardiac injury and rescue heart function, sepsis was induced
      in vivo by caecal ligation and puncture (CLP) surgery, and lipopolysaccharides
      were used as septic stressors for cardiac fibroblasts (CFs) in vitro. The
      expressions of IMD1-53 receptors in sepsis rat heart were increased. After IMD1
      53 treatment, inflammation caused by sepsis in vivo was greatly reduced, as shown
      by the downregulation of apoptosis-associated speck-like protein containing a
      caspase recruitment domain (ASC), nucleotide-binding domain and leucine-rich
      repeat containing family, pyrin containing 3 (NLRP3), pro-IL-1beta, caspase 1,
      and nuclear translocation of nuclear factor-kappaB (NF-kB) protein levels. In
      addition, cardiac function was significantly improved and mean arterial blood
      pressure (MABP) increased by 34.8% (P < 0.05) which almost back to normal.
      Surprisingly, IMD1-53 inhibited cell apoptosis, as caspase 3 activity and Bax
      expression was significantly reduced in the heart upon IMD1-53 treatment. IMD1-53
      abolished the upregulation of ASC, NLRP3, and caspase 1 protein levels in CFs
      induced by lipopolysaccharide (LPS). IMD1-53 increased cell survival rates and
      inhibited IL-1beta production in the cell culture medium. IMD1-53 can protect
      against inflammation and heart injury during sepsis via attenuating the
      NLRP3/caspase-1/IL-1beta pathway.

PMID- 29192368
TI  - Are Anal Sex Roles Associated with Preferences for Pre-Exposure Prophylaxis
      Administration Modalities Among Men Who Have Sex with Men?
AB  - The current study sought to examine awareness of, willingness to use, and
      preferences for available and theoretical administration modalities for HIV pre
      exposure prophylaxis (PrEP) and the association of anal sex roles with these
      concepts among a sample of men who have sex with men (MSM) in Paris, France.
      Broadcast advertisements were placed on a popular geosocial-networking smartphone
      application for MSM to direct users to complete a Web-based survey. MSM answered
      questions on their recent engagement in condomless anal intercourse and awareness
      of and willingness to use PrEP in the form of once daily and event-driven pill
      regimens, long-acting injections, and penile and rectal microbicides as well as
      sexual roles. Multinomial regression models were fit to assess the association
      between behaviorally classified anal sexual role and preferences for one of these
      biomedical prevention modalities. A total of 482 HIV-uninfected MSM completed the
      survey, 48.1% of whom engaged in some form of condomless anal intercourse in the
      preceding 3 months. Most respondents (85.3%) had heard of once daily PrEP, but
      fewer respondents had heard of other prevention strategies. Assuming equal
      effectiveness, long-acting injections were the most commonly preferred (21.8%).
      Behaviorally defined "bottom" and "versatile" MSM more frequently preferred long
      acting injections (32.9% of "bottoms" and 25.3% of "versatiles"). The development
      of long-acting injections to deliver antiretroviral drugs and topical
      microbicides may offer more convenient and acceptable options for HIV prevention
      among MSM, as MSM in this sample were willing to use them and would prefer to use
      them over currently available pill regimens.

PMID- 29192369
TI  - Insurers' Influences on Attending Physicians of Workers Sick-listed for Common
      Mental Disorders: What Are the Impacts on Physicians' Practices?
AB  - Purpose In many jurisdictions, general practitioners (GPs) play an important role
      in the sick-leave and return-to-work (RTW) process of individuals with common
      mental disorders (CMD). Since it is insurers that decide on workers' eligibility
      for disability benefits, they can influence physicians' ability to act. The
      nature of these influences remains little documented to date. The aim of this
      study was therefore to describe these influences and their impacts from the GPs'
      perspective. Methods Semi-structured interviews were conducted with GPs having a
      diversified clientele (n = 13). The interviews were audio-recorded, transcribed
      verbatim and analyzed according to thematic analysis principles. Results The
      results indicated that the GPs recognized insurers as influencing their practices
      with patients on sick leave for CMDs. The documented influences were generally
      seen as constraints, but sometimes as enablers. The impacts of these influences
      on the GPs' practices depended on the organizational characteristics of their
      work context (such as limited consultation time) and other characteristics of
      their practice setting (such as lack of timely access to consultations with
      specialists). Conclusion The results brought three major issues to light: the
      quality of the information sent to insurers by GPs, the respect shown (or not)
      for workers' care preferences, and the relevance of the specialized services
      offered to support workers' RTW. These issues in turn reveal potential risks for
      workers, risks that need to be identified and recognized by all parties concerned
      if we are to come up with possible solutions.

PMID- 29192370
TI  - Directional Hydrodynamic Sensing by Free-Swimming Organisms.
AB  - Many aquatic organisms detect the presence of moving objects in their
      environment, such as predators, by sensing the hydrodynamic disturbances the
      movements produce. The resultant water flow is readily detectable by stationary
      organisms, but free-swimming organisms are carried with the surrounding water and
      may not detect the bulk surrounding flow, which limits the available information
      about the source. We have developed a theory that clarifies what information is
      contained in disturbances generated by an attacking predator that is available to
      a free-swimming organism and might be extracted from local flow deformations
      alone. The theory shows that, depending on how well the deformations can be
      measured in space and time, an organism can reduce the range of possible
      locations, speeds, sizes, and arrival times of the predator. We apply the theory
      to planktonic copepods that have mechanosensory hairs along a pair of antennules.
      The study reveals the presence of "blind spots," potential ambiguities in
      resolving from which of two sides a predator attacks, and whether it generates a
      bow wave or suction. Our findings lead to specific testable hypotheses concerning
      optimal escape strategies, which are helpful for interpreting the behavior of
      evasive prey and designing free-swimming robots with sensory capabilities.

PMID- 29192366
TI  - Blood platelets and sepsis pathophysiology: A new therapeutic prospect in
      critical ill patients?
AB  - Beyond haemostasis, platelets have emerged as versatile effectors of the immune
      response. The contribution of platelets in inflammation, tissue integrity and
      defence against infections has considerably widened the spectrum of their role in
      health and disease. Here, we propose a narrative review that first describes
      these new platelet attributes. We then examine their relevance to
      microcirculatory alterations in multi-organ dysfunction, a major sepsis
      complication. Rapid progresses that are made on the knowledge of novel platelet
      functions should improve the understanding of thrombocytopenia, a common
      condition and a predictor of adverse outcome in sepsis, and may provide potential
      avenues for management and therapy.

PMID- 29192371
TI  - Management of horizontal duodenal perforation: a report of three cases and review
      of literature.
AB  - BACKGROUND: Perforation of the horizontal duodenum is very rare due to the
      presence in retroperitoneal space. It depicts an unusual clinical picture and is
      difficult to diagnose, leading to increased morbidity and mortality. The
      treatment strategies are usually varied and based on small series of cases,
      literature reviews, and expert opinions. CASE PRESENTATION: Here, we presented
      three cases of horizontal duodenal perforation in three different clinical
      processes. The first case, a 30-year-old male patient, presented with abdominal
      pain and hematemesis after experiencing a physical assault on the previous day.
      Computed tomography (CT) scan showed rupture of the horizontal duodenum. It was
      repaired by side-to-side duodenojejunostomy. Postoperatively, he had anastomotic
      leakage, disseminated intravascular coagulation, and pulmonary failure and
      recovered after a long hospital stay. The second case, an 81-year-old female, had
      duodenal perforation with endoscopic coagulation of the bleeding diverticulum.
      Segmental resection of the duodenum and side-to-side duodenojejunostomy were
      performed. Postoperatively, there was slight anastomotic leakage, but surgical
      intervention was not needed. The third case, an 89-year-old female, was a patient
      with obstructive jaundice due to pancreas head carcinoma, who developed
      perforation of the horizontal duodenum during endoscopic retrograde
      cholangiopancreatography (ERCP). After unsuccessful conservative management,
      duodenojejunostomy at the perforated site and gastric bypass were performed. The
      postoperative course was uneventful. CONCLUSION: Early suspicion and
      investigation is necessary for cases of abdominal injuries. CT scan is the
      investigation of choice. The management options should be based on the clinical
      condition of the patient, comorbidities, surgical expertise, existing guidelines,
      and available resources.

PMID- 29192372
TI  - Prediction of Resectability in Pseudomyxoma Peritonei with a New CT Score.
AB  - BACKGROUND: Curative treatment of pseudomyxoma peritonei (PMP) is complete
      cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy
      (HIPEC). OBJECTIVE: The aim of this study was to build and evaluate a
      preoperative imaging score to predict resectability. PATIENTS AND METHODS:
      Between 2007 and 2014, all PMP patients in two tertiary reference centers who
      underwent laparotomy with intent to undergo CRS and HIPEC were included in this
      study retrospectively. Thickness of tumor burden was measured on preoperative
      multidetector-row computed tomography (MDCT) by two radiologists blinded to
      surgical results in five predetermined areas. Patients were divided into two
      cohorts with the same resectability rate (building and validation). The
      performances of the scores were assessed using receiver operating characteristic
      (ROC) curve analyses. RESULTS: Overall, 126 patients were included, with compete
      CRS being achieved in 91/126 patients (72.2%). Two cohorts of 63 patients matched
      by age, sex, burden of disease, resectability rate, and pathological grade were
      constituted. The MDCT score was the sum of the five measures, and was higher in
      unresectable disease [median 46.2 mm (range 27.9-74.6) vs. 0.0 mm (range 0.0
      14.0), p < 0.001]. Area under the ROC curve was 0.863 (range 0.727-0.968) and
      0.801 (range 0.676-0.914) in the building and validation cohorts, respectively. A
      threshold of 28 mm yielded a sensitivity, specificity, positive predictive and
      negative predictive value of 94, 81, 81 and 94% in the building cohort, and 80,
      68, 59 and 85% in the validation cohort, respectively. Using our score, overall
      and disease-free survival were increased in the group classified as resectable.
      CONCLUSION: A simple preoperative MDCT score measuring tumor burden in the
      perihepatic region is able to predict resectability and survival of PMP patients.

PMID- 29192373
TI  - Flexible endoscopically assisted evacuation of acute and subacute subdural
      hematoma through a small craniotomy: preliminary results.
AB  - BACKGROUND: The first choice to treat acute subdural hematoma (SDH) is a large
      craniotomy under general anesthesia. However, increasing age or comorbid burden
      of the patients may render invasive treatment strategy inappropriate. These
      medically frail patients with SDH may benefit from a combination of small
      craniotomy and endoscopic hematoma removal, which is less invasive and even
      available under local anesthesia. Although hematoma evacuation with a rigid
      endoscope for acute or subacute SDHs has been reported in the literature, use of
      a flexible endoscope may have distinct advantages. In this article, we attempted
      to clarify the utility of small craniotomy evacuation with a flexible endoscope
      for acute and subacute SDH in the elderly patients. METHOD: Between November 2013
      and September 2016, a total of 17 patients with acute SDH (15 patients), subacute
      SDH (1 patient), or acute aggravation of chronic SDH (1 patient) underwent
      hematoma evacuation with a flexible endoscope at our hospital and were enrolled
      in this retrospective study. Either under local or general anesthesia, the SDH
      was removed with a flexible suction tube with the aid of the flexible endoscope
      through the small craniotomy (3 * 4 cm). Hematoma evacuation rate, improvement of
      clinical symptoms, and procedure-related complications were evaluated. RESULTS:
      Hematoma evacuation rate was satisfactory, and statistically significant clinical
      improvement was observed in postoperative Glasgow Coma Scale in all cases
      compared to the preoperative assessment. No procedure-related hemorrhagic
      complications were observed. CONCLUSIONS: The results reported here suggest that
      small craniotomy evacuation with a flexible endoscope is a safe, effective, and
      minimally invasive treatment for acute and subacute SDH in selected cases.

PMID- 29192374
TI  - Impact of Bacterial Translocation on Hepatopulmonary Syndrome: A Prospective
      Observational Study.
AB  - BACKGROUND/AIMS: Hepatopulmonary syndrome (HPS) is characterized by a defect in
      oxygenation induced by pulmonary vascular dilatation in cirrhosis. While severe
      HPS is responsible for a high rate of mortality, the prevalence and
      pathophysiology of HPS are not fully elucidated. We evaluated the prevalence and
      pathophysiology of HPS in patients with cirrhosis. METHODS: A total of 142
      patients with cirrhosis who underwent saline-agitated contrast echocardiography
      were enrolled in this prospective observational study. HPS was defined by
      positive findings on contrast echocardiography, cirrhosis, and the presence of an
      oxygenation defect (alveolar-arterial oxygen gradient > 15 mmHg). HPS grades from
      0 to 3 were assigned based on the density and spatial distribution of
      microbubbles in the left ventricle. The primary endpoint was the prevalence of
      HPS. The secondary endpoints included clinical characteristics and levels of
      lipopolysaccharide (LPS), LPS-binding protein (LBP), nitric oxide, and endothelin
      1 in HPS. RESULTS: Fifty-nine patients (41.5%) were diagnosed with HPS (grade 1:
      24, grade 2: 23, and grade 3: 12 patients). The mean levels of LPS (0.36 +/-
      0.02, 1.02 +/- 0.18, 2.86 +/- 0.77, and 6.56 +/- 1.46 EU/mL, p < 0.001) and LBP
      (7026 +/- 3336, 11,445 +/- 1247, 11,947 +/- 1164, and 13,791 +/- 2032 ng/mL, p =
      0.045) were found to be increased according to HPS grade (negative, grade 1-3).
      Endothelin-1 levels were significantly elevated according to HPS grade (1.83 +/-
      0.17, 2.62 +/- 0.22, 3.69 +/- 0.28, and 4.29 +/- 0.34 pg/mL, p < 0.001),
      demonstrating a significant difference between each grade (p < 0.05).
      CONCLUSIONS: HPS is a common complication with a prevalence of 41.5% in patients
      with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation
      are key mechanism involved in the progression of HPS.

PMID- 29192376
TI  - Liver Function Tests "Gone Viral": Acute Hepatitis of Uncertain Cause.

PMID- 29192375
TI  - Efficacy of Rebamipide in Organic and Functional Dyspepsia: A Systematic Review
      and Meta-Analysis.
AB  - OBJECTIVE: The role of gastritis in dyspepsia remains controversial. We aimed to
      examine the efficacy of rebamipide, a gastric mucosal protective agent, in both
      organic and functional dyspepsia. DESIGN: A systematic review and meta-analysis
      was performed. The following databases were searched using the keywords
      ("rebamipide" OR "gastroprotective agent*" OR "mucosta") AND ("dyspepsia" OR
      "indigestion" OR "gastrointestinal symptoms"): PubMed, Wed of Science, Embase,
      CINAHL, Cochrane Clinical Trials Register. The primary outcome was dyspepsia or
      upper GI symptom score improvement. Pooled analysis of the main outcome data were
      presented as risk ratio (RR) for dichotomous data and standardized mean
      difference (SMD) for continuous data. RESULTS: From an initial 248 records, 17
      randomised controlled trial (RCT) publications involving 2170 subjects (1224
      rebamipide, 946 placebo/control) were included in the final analysis. Twelve RCTs
      were conducted in subjects with organic dyspepsia (peptic ulcer disease, reflux
      esophagitis or NSAID-induced gastropathy) and five RCTs were conducted in
      patients with functional dyspepsia (FD). Overall, dyspepsia symptom improvement
      was significantly better with rebamipide compared to placebo/control drug (RR
      0.77, 95% CI = 0.64-0.93; SMD -0.46, 95% CI = -0.83 to -0.09). Significant
      symptom improvement was observed both in pooled RR and SMD in subjects with
      organic dyspepsia (RR 0.72, 95% CI = 0.61-0.86; SMD -0.23, 95% CI = -0.4 to 
      0.07), while symptom improvement in FD was observed in pooled SMD but not RR (SMD
      -0.62, 95% CI = -1.16 to -0.08; RR 1.01, 95% CI = 0.71-1.45). CONCLUSION:
      Rebamipide is effective in organic dyspepsia and may improve symptoms in
      functional dyspepsia.

PMID- 29192377
TI  - How does transient signaling input affect the spike timing of postsynaptic neuron
      near the threshold regime: an analytical study.
AB  - The noisy threshold regime, where even a small set of presynaptic neurons can
      significantly affect postsynaptic spike-timing, is suggested as a key requisite
      for computation in neurons with high variability. It also has been proposed that
      signals under the noisy conditions are successfully transferred by a few strong
      synapses and/or by an assembly of nearly synchronous synaptic activities. We
      analytically investigate the impact of a transient signaling input on a leaky
      integrate-and-fire postsynaptic neuron that receives background noise near the
      threshold regime. The signaling input models a single strong synapse or a set of
      synchronous synapses, while the background noise represents a lot of weak
      synapses. We find an analytic solution that explains how the first-passage time
      (ISI) density is changed by transient signaling input. The analysis allows us to
      connect properties of the signaling input like spike timing and amplitude with
      postsynaptic first-passage time density in a noisy environment. Based on the
      analytic solution, we calculate the Fisher information with respect to the
      signaling input's amplitude. For a wide range of amplitudes, we observe a non
      monotonic behavior for the Fisher information as a function of background noise.
      Moreover, Fisher information non-trivially depends on the signaling input's
      amplitude; changing the amplitude, we observe one maximum in the high level of
      the background noise. The single maximum splits into two maximums in the low
      noise regime. This finding demonstrates the benefit of the analytic solution in
      investigating signal transfer by neurons.

PMID- 29192378
TI  - Comparing Parental Well-Being and Its Determinants Across Three Different Genetic
      Disorders Causing Intellectual Disability.
AB  - Using the Short Form 12 Health Survey this cross-sectional study examined
      parental well-being in caregivers of children with one of three genetic disorders
      associated with intellectual disability; Down syndrome, Rett syndrome and the
      CDKL5 disorder. Data were sourced from the Western Australian Down Syndrome (n =
      291), Australian Rett Syndrome (n = 187) and International CDKL5 Disorder (n =
      168) Databases. Among 596 mothers (median age, years 43.7; 24.6-72.2), emotional
      well-being was poorer than general female populations across age groups.
      Multivariate linear regression identified the poorest well-being in parents of
      children with the CDKL5 disorder, a rare but severe and complex encephalopathy,
      and negative associations with increased clinical severity irrespective of
      diagnosis. These findings are important for those providing healthcare and social
      services for these populations.

PMID- 29192379
TI  - Emotion Regulation Strategies in Preschoolers with Autism: Associations with
      Parent Quality of Life and Family Functioning.
AB  - Children with autism experience challenges with emotion regulation. It is unclear
      how children's management of their emotions is associated with their family's
      quality of life. Forty-three preschoolers with autism and 28 typically developing
      preschoolers were coded on emotion regulation strategies used during low-level
      stress tasks. Parents reported on their quality of life and family functioning,
      and their child's internalizing and externalizing behaviors. More externalizing
      behaviors across groups and use of two emotion regulation strategies (self
      soothing, deep exhalation) in the autism group predicted lower family quality of
      life. Findings suggest that children's emotional outbursts and reduced use of
      passive comforting strategies are linked to lower family quality of life.

PMID- 29192380
TI  - A population-level study examining discontinuation of statins in older people
      with dementia.

PMID- 29192383
TI  - Announcement: New initiative 'case presentation corner'.

PMID- 29192381
TI  - ABCB6, an ABC Transporter Impacting Drug Response and Disease.
AB  - Recent findings have discovered how insufficiency of ATP-binding cassette (ABC)
      transporter, ABCB6, can negatively impact human health. These advances were made
      possible by, first, finding that ABCB6 deficiency was the genetic basis for some
      severe transfusion reactions and by, second, determining that functionally
      impaired ABCB6 variants enhanced the severity of porphyria, i.e., diseases
      associated with defects in heme synthesis. ABCB6 is a broad-spectrum porphyrin
      transporter that is capable of both exporting and importing heme and its
      precursors across the plasma membrane and outer mitochondrial membrane,
      respectively. Biochemical studies have demonstrated that while ABCB6 influences
      the antioxidant system by reducing the levels of reactive oxygen species, the
      exact mechanism is currently unknown, though effects on heme synthesis are
      likely. Furthermore, it is unknown what biochemical or cellular signals determine
      where ABCB6 localizes in the cell. This review highlights the major recent
      findings on ABCB6 and focuses on details of its structure, mechanism, transport,
      contributions to cellular stress, and current clinical implications.

PMID- 29192382
TI  - Multimodal molecular 3D imaging for the tumoral volumetric distribution
      assessment of folate-based biosensors.
AB  - The aim of this study was to characterize the in vivo volumetric distribution of
      three folate-based biosensors by different imaging modalities (X-ray,
      fluorescence, Cerenkov luminescence, and radioisotopic imaging) through the
      development of a tridimensional image reconstruction algorithm. The preclinical
      and multimodal Xtreme imaging system, with a Multimodal Animal Rotation System
      (MARS), was used to acquire bidimensional images, which were processed to obtain
      the tridimensional reconstruction. Images of mice at different times (biosensor
      distribution) were simultaneously obtained from the four imaging modalities. The
      filtered back projection and inverse Radon transformation were used as main image
      processing techniques. The algorithm developed in Matlab was able to calculate
      the volumetric profiles of 99mTc-Folate-Bombesin (radioisotopic image), 177Lu
      Folate-Bombesin (Cerenkov image), and FolateRSenseTM 680 (fluorescence image) in
      tumors and kidneys of mice, and no significant differences were detected in the
      volumetric quantifications among measurement techniques. The imaging
      tridimensional reconstruction algorithm can be easily extrapolated to different
      2D acquisition-type images. This characteristic flexibility of the algorithm
      developed in this study is a remarkable advantage in comparison to similar
      reconstruction methods.

PMID- 29192384
TI  - Spin states of Mn(III) meso-tetraphenylporphyrin chloride assessed by density
      functional methods.
AB  - The present work assessed several exchange-correlation functionals (including
      GGA, meta-GGA and hybrid functionals), in combination with a variety of basis
      sets and effective core potentials (ECP) for their ability to predict the ground
      spin state of Mn(III) meso-tetraphenylporphyrin chloride complex, labeled
      Mn(III)TPPCl, for which experimental data support the quintet high spin state.
      Geometry optimization of Mn(III)TPPCl was performed for three possible spin
      states (singlet state, LS; triplet state, IS; and quintet state, HS) at the TPSSh
      level using the LANL2DZ ECP for Mn and the 6-311G(d) basis set for C, N, Cl and
      H. Afterwards, single-point energy calculations were conducted by applying 18
      exchange-correlation functionals (BLYP, B3LYP, PW91, BPW91, BP86, OLYP, OPBE,
      OPW91, O3LYP, PBE0, PBEh1PBE, HSEH1PBE, TPSS, TPSSh, M06 L, M06, M062X and
      M06HF). The influence of the basis set for the metal center was assessed using a
      smaller group of functionals and varying between the Pople basis set 6-31G(d),
      its newer formulation m6-31G(d) and the larger Def2-QZVP basis set. All
      functionals in combination with Pople basis sets predict the quintet state as the
      ground spin state. In addition, the BLYP, BP86, BPW91, PW91, PBEh1PBE, TPSS and
      TPSSh functionals predicted the IS lying at most ~60 kJ mol-1 above the HS, which
      agrees with the reference data. Results including Def2-QZVP basis set were
      inconsistent, since only BLYP and B3LYP predict HS as the ground spin state. The
      recommended methodology for the treatment of such systems seems to be exchange
      correlations functionals with few or none Hartree-Fock exchange and modest size
      basis sets. Graphical Abstract MnTPPCl molecule and the energy ordering of its
      spin states assessed by 18 functionals.

PMID- 29192385
TI  - Choledocholithiasis after Bariatric Surgery-More than a Stone's Throw to Reach?
AB  - BACKGROUND: Gallstone disease is common after bariatric surgery, and patients
      with bile duct stones in this cohort can be difficult to treat, due to the
      altered anatomy. This review aims to analyse the various management options
      available for choledocholithiasis in post-bariatric surgery patients. METHODS: A
      literature search of PubMed, Medline and Cochrane library databases was carried
      out for studies on this subject, between January 1970 and March 2017. After
      initial screening and further full text review, suitable studies were identified
      after applying the inclusion criteria. RESULTS: Twenty-nine studies were
      identified and analysed. Overtube-assisted endoscopy appears to be a popular
      technique, and 10 studies employing this technique were identified. Though there
      are minor variations between the three different types of overtube endoscopy, the
      success rate for ERCP with this approach is between 60 and 70%. Studies using a
      combination of radiological and endoscopic techniques report a success rate of 60
      70%, though the endoscopic ultrasound-guided technique has been reported to have
      higher success rates (90-100%). Surgery-assisted ERCP also appears to be widely
      reported and has a consistently high ERCP success rate (80-100%), with an added
      advantage of the option to perform a concomitant cholecystectomy. There are very
      few reports on using surgery as the sole option in this scenario. CONCLUSION:
      Both overtube-assisted endoscopy and laparoscopy-assisted ERCP appear to be safe,
      with good success rates. The other methods may be suitable for selected patients
      and centres with specific interest in such techniques.

PMID- 29192386
TI  - Sequential Neighborhood Effects: The Effect of Long-Term Exposure to Concentrated
      Disadvantage on Children's Reading and Math Test Scores.
AB  - Prior research has suggested that children living in a disadvantaged neighborhood
      have lower achievement test scores, but these studies typically have not
      estimated causal effects that account for neighborhood choice. Recent studies
      used propensity score methods to account for the endogeneity of neighborhood
      exposures, comparing disadvantaged and nondisadvantaged neighborhoods. We develop
      an alternative propensity function approach in which cumulative neighborhood
      effects are modeled as a continuous treatment variable. This approach offers
      several advantages. We use our approach to examine the cumulative effects of
      neighborhood disadvantage on reading and math test scores in Los Angeles. Our
      substantive results indicate that recency of exposure to disadvantaged
      neighborhoods may be more important than average exposure for children's test
      scores. We conclude that studies of child development should consider both
      average cumulative neighborhood exposure and the timing of this exposure.

PMID- 29192387
TI  - Differences in Child Health Across Rural, Urban, and Slum Areas: Evidence From
      India.
AB  - The developing world is rapidly urbanizing, but an understanding of how child
      health differs across urban and rural areas is lacking. We examine the
      association between area of residence and child health in India, focusing on
      composition and selection effects. Simple height-for-age averages show that rural
      Indian children have the poorest health and urban children have the best, with
      slum children in between. With wealth or observed health environment held
      constant, the urban height-for-age advantage disappears, and slum children fare
      significantly worse than their rural counterparts. Hence, differences in
      composition across areas mask a substantial negative association between living
      in slums and height-for-age. This association is more negative for girls than
      boys. Furthermore, a large number of girls are "missing" in slums; we argue that
      this implies that the negative association between living in slums and health is
      even stronger than our estimate. The missing girls also help explain why slum
      girls appear to have a substantially lower mortality than rural girls, whereas
      slum boys have a higher mortality risk than rural boys. We estimate that slum
      conditions (such as overcrowding and open sewers), which the survey does not
      adequately capture, are associated with 20 % to 37 % of slum children's stunting
      risk.

PMID- 29192389
TI  - Backwards and Forwards.

PMID- 29192388
TI  - Tumor cell-intrinsic phenotypic plasticity facilitates adaptive cellular
      reprogramming driving acquired drug resistance.
AB  - The enthusiasm about successful novel therapeutic strategies in cancer is often
      quickly dampened by the development of drug resistance. This is true for targeted
      therapies using tyrosine kinase inhibitors for EGFR or BRAF mutant cancers, but
      is also an increasingly recognized problem for immunotherapies. One of the major
      obstacles of successful cancer therapy is tumor heterogeneity of genotypic and
      phenotypic features. Historically, drivers for drug resistance have been
      suspected and found on the genetic level, with mutations either being pre
      existing in a subset of cancer cells or emerging de novo to mediate drug
      resistance. In contrast to that, our group and others identified a non-mutational
      adaptive response, resulting in a reversible, drug tolerant, slow cycling
      phenotype that precedes the emergence of permanent drug resistance and is
      triggered by prolonged drug exposure. More recently, studies described the
      importance of initially reversible transcriptional reprogramming for the
      development of acquired drug resistance, identified factors important for the
      survival of the slow cycling phenotype and investigated the relationship of
      mutational and non-mutational resistance mechanisms. However, the connection and
      relative importance of mutational and adaptive drug resistance in relation to the
      in vitro models at hand and the clinically observed response patterns remains
      poorly defined. In this review we focus on adaptive intrinsic phenotypic
      plasticity in cancer cells that leads to the drug tolerant slow cycling state,
      which eventually transitions to permanent resistance, and propose a general model
      based on current literature, to describe the development of acquired drug
      resistance.

PMID- 29192391
TI  - IL-21 as a Predictor of Sustained Virologic Response in Patients with Chronic
      Hepatitis C Virus Infection.
AB  - Hepatitis C virus (HCV) infection is a significant public health problem. The
      crucial role of interleukin (IL)-21 in HCV has been established. Thus, we aimed
      to investigate the association of serum IL-21 levels with the virological
      response to interferon (IFN)-based therapy in a group of Egyptian patients with
      chronic hepatitis C (CHC). Clinical data were collected from 58 HCV-positive
      Egyptian patients treated with IFN/ribavirin therapy and 10 non-HCV-infected
      healthy subjects. Liver and renal function tests, complete blood count, viral
      markers, and pretreatment IL-21 levels were determined in all patients and
      healthy controls. Patients who achieved sustained virologic response (SVR) had
      higher pretreatment median serum IL-21 levels than those who did not. Thus, this
      study concluded that higher pretreatment serum IL-21 may be useful in predicting
      SVR in CHC patients.

PMID- 29192390
TI  - EpCAM-based assays for epithelial tumor cell detection in cerebrospinal fluid.
AB  - The diagnosis of leptomeningeal metastases (LM) of solid tumors is complicated
      due to low sensitivities of both magnetic resonance imaging (MRI) and cytology.
      MRI has a sensitivity of 76% for the diagnosis of LM and cerebrospinal fluid
      (CSF) cytology has a sensitivity of 44-67% at first lumbar puncture which
      increases to 84-91% upon second CSF sampling. Epithelial cell adhesion molecule
      (EpCAM) is expressed by solid tumors of epithelial origin like non-small-cell
      lung cancer, breast cancer or ovarium cancer. Recently, a CELLSEARCH(r) assay and
      flow cytometry laboratory techniques have been developed to detect circulating
      tumor cells (CTCs) of epithelial origin in CSF. These laboratory techniques are
      based on capture antibodies labelled with different fluorescent tags against
      EpCAM. In this review, we provide an overview of the available laboratory
      techniques and diagnostic accuracy for tumor cell detection in CSF. The reported
      sensitivities of the EpCAM-based CTC assays for the diagnosis of LM across the
      different studies are highly promising and vary between 76 and 100%. An overview
      of the different EpCAM-based techniques for the enumeration of CTCs in the CSF is
      given and a comparison is made with CSF cytology for the diagnoses of LM from
      epithelial tumors.

PMID- 29192392
TI  - Risks posed by neutron contamination in high energy radiotherapy.

PMID- 29192394
TI  - Withholding and withdrawing life support: difficult decisions around care at the
      end of life.

PMID- 29192395
TI  - Intracrystalline Ozurdex(r): therapeutic effect maintained for 18 months.
AB  - INTRODUCTION: Ozurdex(r) is a sterile, sustained-release implant of
      dexamethasone. The device dissolves within the vitreous body and releases
      dexamethasone. Here we present a clinical case that demonstrates the sustained
      therapeutic efficacy of Ozurdex(r) when accidentally injected into the
      crystalline lens. METHODS: Case report. RESULTS: Sixty-three-year-old male in
      which we decided to prescribe the intravitreal injection of a dexamethasone
      implant (Ozurdex(r)) in the left eye because of macular oedema after branch
      retinal vein occlusion. Best-corrected visual acuity (BCVA) was 0.4. At 15 days
      post-implantation, the slit-lamp examination revealed the dexamethasone implant
      was located in the crystalline lens. Given there was no inflammation in the
      anterior pole, no cataracts had developed, the intraocular pressure (IOP) was
      normal and the macular oedema had been resolved, we decided to assess the
      efficacy and safety of the dexamethasone implant located in the crystalline lens.
      The BCVA improved until 14 months post-accidental injection. At 18 months post
      Ozurdex(r) injection the BCVA worsened until 0.05 because of the cataract
      evolution. Phacoemulsification and intraocular lens placement in sulcus was
      performed. CONCLUSION: Once the complication has occurred, most authors advocate
      the early withdrawal of the implanted Ozurdex(r) device by means of crystalline
      phacoemulsification and then repositioning it in the vitreous body. However, as
      long as there are no signs of inflammation in the anterior pole, the IOP is
      within normal limits, the device does not affect the visual axis and there is no
      cataract development, we can evaluate the potential therapeutic effect of
      Ozurdex(r) in this non-indicated, abnormal location.

PMID- 29192396
TI  - Insights into the Synergistic Biodegradation of Waste Papers Using a Combination
      of Thermostable Endoglucanase and Cellobiohydrolase from Chaetomium thermophilum.
AB  - Enzymatic hydrolysis is considered an efficient and environmental strategy for
      the degradation of organic waste materials. Compared to mesophilic cellulases,
      thermostable cellulases with considerable activity are more advantageous in waste
      paper hydrolysis, particularly in terms of their participation in synergistic
      action. In this study, the synergistic effect of two different types of
      thermostable Chaetomium thermophilum cellulases, the endoglucanase CTendo45 and
      the cellobiohydrolase CtCel6, on five common kinds of waste papers was
      investigated. CtCel6 significantly enhanced the bioconversion process, and
      CTendo45 synergistically increased the degradation, with a maximum degree of
      synergistic effect of 1.67 when the mass ratio of CTendo45/CtCel6 was 5:3. The
      synergistic degradation products of each paper material were also determined.
      Additionally, the activities of CTendo45 and CtCel6 were found to be insensitive
      to various metals at 2 mM and 10 mM ion concentrations. This study gives an
      initial insight into a satisfactory synergistic effect of C. thermophilum
      thermostable cellulases for the hydrolysis of different paper materials, which
      provides a potential combination of enzymes for industrial applications,
      including environmentally friendly waste management and cellulosic ethanol
      production.

PMID- 29192397
TI  - Ustekinumab for Treating Moderately to Severely Active Crohn's Disease after
      Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology
      Appraisal.
AB  - As part of the single technology appraisal (STA) process, the National Institute
      for Health and Care Excellence (NICE) invited Janssen to submit evidence on the
      clinical and cost effectiveness of their drug ustekinumab, an interleukin-12/23
      inhibitor, for treating moderate-to-severe active Crohn's disease (CD). The
      Centre for Reviews and Dissemination (CRD) and Centre for Health Economics (CHE)
      Technology Appraisal Group at the University of York was commissioned to act as
      the independent Evidence Review Group (ERG). This article provides a description
      of the Company's submission, the ERG's critical review of submitted evidence, and
      the resulting NICE guidance. The main supporting clinical evidence was derived
      from four well conducted, randomised controlled trials, comparing ustekinumab
      with placebo in two sub-populations (conventional care failure and anti-TNFalpha
      failure patients) of adults with moderate-to-severe CD. Three trials assessed
      treatment induction over 8 weeks, while the fourth recruited successfully induced
      patients into a maintenance trial for 1 year. These trials showed ustekinumab to
      be more effective than placebo in terms of its ability to induce and maintain
      clinical response and remission. In the absence of any direct head-to-head data,
      the Company conducted a network meta-analysis (NMA), which synthesised induction
      trial data on ustekinumab and relevant comparators (vedolizumab, adalimumab and
      infliximab) using placebo data as a common comparator. This analysis found
      ustekinumab to be of comparable efficacy to previously approved biologics in
      treatment induction. A 'treatment sequence analysis' compared long-term treatment
      efficacy, finding ustekinumab to be comparable in maintaining treatment response
      and remission to the three other biologic therapies. However, the ERG had
      identified many limitations and potential bias in this analysis, and urged
      caution when interpreting the results. The Company's economic model estimated
      ustekinumab to be dominant in both sub-populations compared with conventional
      care; however, the ERG's preferred base-case estimated an incremental cost
      effectiveness ratio of L109,279 in the conventional care failure sub-population,
      and L110,967 in the anti-TNFalpha failure sub-population when compared with
      conventional care. However, the ERG identified significant failings in both the
      model structure and data inputs, which could not be addressed without complete
      restructuring. The ERG considered that the economic analysis presented by the
      Company failed to adequately address the decision problem specified in NICE's
      scope. The NICE Appraisal Committee recommended ustekinumab within its market
      authorisation, on the grounds of sufficiently similar efficacy and costs to
      previously recommended biologic therapies. However, the ERG's analyses
      demonstrated that all currently recommended biologics are unlikely to be cost
      effective relative to conventional care, raising broader questions regarding the
      appropriateness of cost-comparison exercises for decision making.

PMID- 29192398
TI  - Water quality in simulated eutrophic shallow lakes in the presence of periphyton
      under different flow conditions.
AB  - Although the effects of periphyton on water quality and its relationship with
      flow conditions have been studied by researchers, our understanding about their
      combined action in eutrophic shallow lakes is poor. In this research, four
      aquatic model ecosystems with different water circulation rates and hydraulic
      conditions were constructed to investigate the effect of periphyton and flow
      condition on water quality. The concentrations of NH4+, TP, and chlorophyll-a and
      flow conditions were determined. The results show that, as a result of the rising
      nutrient level at the early stage and the decline in the lower limit, the
      presence of periphyton can make the ecosystem adaptable to a wider range of
      nutrients concentration. In terms of the flow condition, the circulation rate and
      hydraulic condition are influential factors for aquatic ecosystem. Higher
      circulation rate in the ecosystem, on one hand, facilitates the metabolism by
      accelerating nutrient cycling which is beneficial to water quality; on the other
      hand, high circulation rate leads to the nutrient lower limit rising which is
      harmful to water quality improvement. At low velocities, slight differences in
      hydraulic conditions, vertical velocity gradient and turbulence intensity
      gradient could affect the quantity of phytoplankton. Our study suggests that,
      considering environmental effect of periphyton, flow conditions and their
      combined action is essential for water quality improvement and ecological
      restoration in eutrophic shallow lakes.

PMID- 29192399
TI  - Indoor air quality of everyday use spaces dedicated to specific purposes-a
      review.
AB  - According to literature data, some of the main factors which significantly affect
      the quality of the indoor environment in residential households or apartments are
      human activities such as cooking, smoking, cleaning, and indoor exercising. The
      paper presents a literature overview related to air quality in everyday use
      spaces dedicated to specific purposes which are integral parts of residential
      buildings, such as kitchens, basements, and individual garages. Some aspects of
      air quality in large-scale car parks, as a specific type of indoor environment,
      are also discussed. All those areas are characterized by relatively short time
      use. On the other hand, high and very high concentration levels of xenobiotics
      can be observed, resulting in higher exposure risk. The main compounds or group
      of chemical compounds are presented and discussed. The main factors influencing
      the type and amount of chemical pollutants present in the air of such areas are
      indicated.

PMID- 29192400
TI  - Historical anthropogenic mercury in two lakes of Central Chile: comparison
      between an urban and rural lake.
AB  - Mercury concentrations in the environment tend to decrease in recent years due to
      environmental restrictions. Lakes store mercury in their sediments, making them
      potential secondary contamination sources. In South America, the occurrence of
      mercury in lake systems has been associated mainly with volcanic emissions and
      only few records anthropogenic contamination in the pre-Hispanic period. The
      objective of this research was to study historical anthropogenic mercury
      concentration in two lakes in Central Chile (La Senoraza and Pillo), in order to
      establish background mercury levels and their variations from preindustrial to
      modern periods. Different background levels and mercury concentrations were found
      in each lake, with significantly higher concentrations in Lake La Senoraza during
      the last 150 years. Mining-related activities during the nineteenth century could
      have a negligible influence on mercury concentrations. Later on, the use of coal
      railroads and subsequent employment of mercury in the cellulose industry were
      associated with three- and fourfold increases in mercury concentration over the
      nineteenth century background levels, which decrease once these activities
      ceased. However, in the case of Lake Pillo, an important increase in mercury
      concentration can be observed between 1990 and the early twenty-first century,
      which could be related to a higher watershed/lake area ratio, extensive
      agriculture, and volcanic emission, being the latter that could have contributed
      with mercury to both systems. Nevertheless, sedimentological characteristics in
      Lake Pillo can be favorable to retain mercury in this aquatic system up to the
      present day.

PMID- 29192401
TI  - Spatio-temporal evaluation of emerging contaminants and their partitioning along
      a Brazilian watershed.
AB  - The occurrence, partitioning, and spatio-temporal distribution of seven
      pharmaceuticals for human use, three steroid hormones and one personal care
      product were determined in surface water, suspended particulate matter (SPM), and
      sediment of Pirai Creek and Jundiai River (Jundiai River Basin, Sao Paulo,
      Brazil). The maximum average detected concentrations of the compounds in the
      Pirai River samples were < 30 ng L-1, except for caffeine (222 ng L-1). In
      Jundiai River samples, most of the compounds were frequently detected, wherein
      caffeine had the highest concentration, with maximum average concentrations of
      14,050 ng L-1, followed by atenolol (431 ng L-1), ibuprofen (268 ng L-1) and
      diclofenac (214 ng L-1). Atenolol, propranolol, estrone, and triclosan were the
      contaminants most frequently detected in sediment and SPM samples. Triclosan had
      the highest average proportion of SPM as opposed to in the aqueous phase (> 75%).
      Contaminants with acid functional groups showed, in general, a lower tendency to
      bind to particulate matter and sediments. In addition, hydrophobicity had an
      important effect on their environmental partitioning. The spatial distribution of
      contaminants along the Jundiai River was mainly affected by the higher
      concentration of contaminants in water samples collected downstream from a sewage
      treatment plant (STP). The results obtained here clearly showed the importance of
      the analysis of some contaminants in the whole water, meaning both dissolved and
      particulate compartments in the water, and that the partitioning is ruled by a
      set of parameters associated to the physicochemical characteristics of
      contaminants and the matrix properties of the studied, which need be considered
      in an integrated approach to understand the fate of emerging chemical
      contaminants in aquatic environments.

PMID- 29192402
TI  - Comparative studies on the performance and emissions of a direct injection diesel
      engine fueled with neem oil and pumpkin seed oil biodiesel with and without fuel
      preheater.
AB  - In the present experimental analysis, two non-edible oils namely neem oil and
      pumpkin seed oil were considered. They are converted into respective biodiesels
      namely neem oil methyl ester (B1) and pumpkin seed oil methyl ester (B2) through
      transesterification process and their physical and chemical properties were
      examined using ASTM standards. Diesel was used as a baseline fuel in Kirloskar
      TV1 model direct injection four stroke diesel engine. A fuel preheater was
      designed and fabricated to operate at various temperatures (60, 70, and 80 
      degrees C). Diesel showed higher brake thermal efficiency (BTE) than biodiesel
      samples. Lower brake specific fuel consumption (BSFC) was obtained with diesel
      than B1 sample. B1 exhibited lower BSFC than B2 sample without preheating
      process. High preheating temperature (80  degrees C) results in lower fuel
      consumption for B1 sample. The engine emission characteristics like carbon
      monoxide (CO), hydrocarbon (HC), and smoke were found lower with B1 sample than
      diesel and B2 except oxides of nitrogen (NOx) emission. In preheating of fuel, B1
      sample with high preheating temperature showed lower CO, HC, and smoke emission
      (except NOx) than B2 sample.

PMID- 29192403
TI  - Transformation of sulfaquinoxaline by chlorine and UV light in water: kinetics
      and by-product identification.
AB  - Sulfaquinoxaline (SQX) is an antimicrobial of the sulfonamide class, frequently
      detected at low levels in drinking and surface water as organic micropollutant.
      The main goal of the present study is the evaluation of SQX reactivity during
      chlorination and UV irradiations which are two processes mainly used in water
      treatment plants. The SQX transformation by chlorination and UV lights (254 nm)
      was investigated in purified water at common conditions used for water
      disinfection (pH = 7.2, temperature = 25  degrees C, [chlorine] = 3 mg L-1). The
      result shows a slow degradation of SQX during photolysis compared with
      chlorination process. Kinetic studies that fitted a fluence-based first-order
      kinetic model were used to determine the kinetic constants of SQX degradation;
      they were equal to 0.7 * 10-4 and 0.7 * 10-2 s-1corresponding to the half time
      lives of 162 and 1.64 min during photolysis and chlorination, respectively. In
      the second step, seven by-products were generated during a chlorination and photo
      transformation of SQX and identified using liquid chromatography with
      electrospray ionization and tandem mass spectrometry (MS-MS). SO2 extrusion and
      direct decomposition were the common degradation pathway during photolysis and
      chlorination. Hydroxylation and isomerization were observed during
      photodegradation only while electrophilic substitution was observed during
      chlorination process.

PMID- 29192405
TI  - Development of Itraconazole Tablets Containing Viscous KinetiSol Solid
      Dispersions: In Vitro and In Vivo Analysis in Dogs.
AB  - The formulation factors relevant to developing immediate and controlled release
      dosage forms containing poorly soluble drugs dispersed in amorphous systems are
      poorly understood. While the utility of amorphous solid dispersions is becoming
      apparent in the pharmaceutical marketplace, literature reports tend to
      concentrate on the development of solid dispersion particulates, which then must
      be formulated into a tablet. Amorphous solid dispersions of itraconazole in high
      molecular weight hydroxypropyl methylcellulose were prepared by KinetiSol(r)
      Dispersing and tablets were formulated to immediately disintegrate or control the
      release of itraconazole. Formulated tablets were evaluated by two non-sink
      dissolution methodologies and the dosage form properties that controlled the
      gelling tendency of the dispersion carrier, hydroxypropyl methylcellulose, were
      investigated. Selected formulations were evaluated in an exploratory beagle dog
      pharmacokinetic study; the results of which indicate potential for a prolonged
      absorption phase relative to the commercially extruded control.

PMID- 29192404
TI  - Effects of lead, cadmium, chromium, and arsenic on the sorption of lindane and
      norfloxacin by river biofilms, particles, and sediments.
AB  - The sorption of both classic and emerging organic contaminants onto aquatic
      solids is a critical process that controls their fate in natural waters. Sorption
      is affected by numerous factors, including coexisting heavy metals. The
      mechanisms of the influence of heavy metals, especially those occurring in acid
      radical anions, are still unclear. Here, the effects of Pb, Cd, Cr, and As on the
      sorption of lindane and norfloxacin (NOR) onto natural biofilms, suspended
      particles, and sediments from one river were investigated following batch
      equilibration methods. In addition, changes in representative components that
      have important roles in sorption from these solids in the presence and absence of
      metals were characterized by spectrum analyses. The results indicated that
      sorption of lindane and NOR on the three solids in the absence of heavy metals
      was highly linear and nonlinear, respectively. Pb and Cd promoted and Cr and As
      suppressed hydrophobic lindane sorption on the three solids. This was because Pb
      and Cd enhanced but Cr and As weakened the hydrophobicity of these solids. Pb,
      Cd, Cr, and As decreased NOR sorption on sediments and suspended particles at pH
      5.7~6.3. This was due to electrostatic competition between cationic Pb/Cd and
      NORH2+, and the combination of Cr/As acid radicals with NORH2+, which suppressed
      its ion-exchange adsorption. Pb, Cd, Cr, and As generally increased the sorption
      of NOR onto the biofilms at pH 5.7~6.3. Pb and Cd strengthened the flocculation
      of dissolved organic matter combined with NORH2+ onto the biofilms. Cr and As
      enhanced the hydrophilicity of biofilms, and then increased their sorption of NOR
      with active hydrophilic groups. The mechanisms of how different heavy metals
      affect NOR sorption by biofilms were more complicated than the mechanisms
      affecting lindane sorption, as well as by sediments and particles.

PMID- 29192406
TI  - Gastric Gastrointestinal Stromal Tumors (GIST): a Case Series and Current State
      of the Art in the Workup and Treatment of This Rare Disease.

PMID- 29192407
TI  - De novo lipogenesis and desaturation of fatty acids during adipogenesis in bovine
      adipose-derived mesenchymal stem cells.
AB  - Adipose-derived mesenchymal stem cells (ADSCs) are useful cell model to study
      adipogenesis and energy metabolism. However, the biological characteristics of
      bovine ADSCs (bADSCs) remain unclear. This study aimed to isolate and identify
      bADSCs and further investigate fatty acid (FA)-related gene expression and
      composition of FAs during adipogenesis. The growth curve showed the bADSCs of P5
      cells had rapid proliferation superior to P10-P50. The colony formation assay
      showed colony number of P5 cells was higher than that of P50 cells (51.67 +/-
      3.06 vs 35.67 +/- 6.43, P < 0.05). The immunofluorescence showed that bADSCs were
      positive for CD13, CD44, CD49d, CD90, CD105, and Vimentin while negative for
      CD34. The multipotential towards adipocyte, osteocyte, and chondrocyte was
      confirmed by specific histological staining and lineage gene expression. During
      adipogenic induction, the genes related to lipogenesis and lipolysis were
      assessed by real-time PCR and the FA composition was detected by GC-MS.
      Expression of lipogenesis-related genes showed coordinated regulation as peaking
      on day 7 and declining until induction ended, including PPARgamma, SREBP1, ACC1,
      FAS, ELOVL6, SCD1, and FABP4. FA deposition-related genes (DGAT1 and ACAT1)
      increased until day 14. Lipolysis genes (CPT-1A, VLCAD, and ACO) showed a variant
      expression pattern. The profile of FAs showed that proportion of the FAs (C4-C15,
      >= C22) increased, but proportion of long-chain fatty acids (C16-C20) reduced
      after induction. And saturated FAs (SFA) decreased while monounsaturated FAs
      (MUFA) and polyunsaturated FAs (PUFA) increased during adipogenesis. These data
      suggest that bADSCs possess the characteristics of mesenchymal stem cells and
      have active de novo lipogenesis (DNL) and desaturation of FAs during
      adipogenesis.

PMID- 29192409
TI  - What's in a Word?

PMID- 29192408
TI  - Prolonged delivery of BMP-2 by a non-polymer hydrogel for bone defect
      regeneration.
AB  - Bone morphogenetic protein 2 (BMP-2) is a potent inducer of bone formation that
      is currently used in a limited number of clinical indications to treat extensive
      bone loss. Extending the field of applications of this molecule requires design
      of the delivery system to protect the protein from early degradation and allow a
      slow long-term release. This study describes the use of a non-polymer hydrogel,
      based on the self-assembly of small amphiphilic glycosyl-nucleolipids into
      micellar structures, as a new type of delivery system for BMP-2. BMP-2 was
      readily encapsulated in glycosyl-nucleosyl-fluorinated (GNF)-based gels and
      slowly released in vitro, while maintaining its osteogenic activity. When
      hydrogel pieces containing fluorophore-tagged BMP-2 were deposited onto a
      calvaria defect in mouse, the signal detected in living mice gradually decreased
      and was still detectable at 3 weeks. Gel-embedded protein promoted significant
      calvarial bone defect regeneration at 8 weeks after surgery. In contrast, when a
      solution of BMP-2 without hydrogel was injected into the defects, the
      fluorescence signal decreased rapidly and no significant bone formation was
      observed. The unique property of the GNF-based hydrogel as an injectable delivery
      system for low doses of BMP-2 was revealed in a subcutaneous model of ectopic
      bone formation. Injected BMP-2-laden GNF hydrogel blocks elicited the formation
      of cancellous bone, showing all the typical features of remodeling bone that
      contains bone marrow. These results show that this GNF-based hydrogel is an easy
      to-use, efficient delivery system for BMP-2 and osteogenic material to support
      bone regeneration.

PMID- 29192410
TI  - Simulating Clinical Psychiatry for Medical Students: a Comprehensive Clinic
      Simulator with Virtual Patients and an Electronic Medical Record System.
AB  - OBJECTIVE: A number of programs representing virtual patients for use in teaching
      settings have been developed in the field of psychiatry; however, they simulate
      only the interview process, not the entire scope of treatment. The authors have
      developed software through which students can experience the practice of
      psychiatry (in particular, with dementia patients) in its entirety. This study
      compares this software with conventional learning methods. METHOD: The control
      group was 43 fifth-year medical students in 2014 who studied using a conventional
      learning method (taking lectures and being in contact with actual patients). The
      experimental group was 36 fifth-year medical students in 2015 that used computer
      software (taking lectures and with reduced time in contact with actual patients).
      The authors compared the two groups. Each group was tested before and after
      clinical training on their acquisition of knowledge of dementia. The control
      group was tested in 2014, and the experimental group was tested in 2015. RESULTS:
      The difference in average test scores between the two groups was statistically
      significant (p = 0.01), with the experimental group scoring higher. CONCLUSIONS:
      The results indicate that students who were taught using a computer-based
      software method were better able to answer a standard series of questions
      designed to evaluate their understanding of dementia than those who were taught
      in a conventional manner. This study demonstrated that there is a possibility to
      improve education in the field of psychiatry using a comprehensive clinic
      simulator.

PMID- 29192411
TI  - Increased serum neuregulin 4 levels in women with polycystic ovary syndrome: A
      case-control study.
AB  - Neuregulin 4 (NRG4) is an adipokine that is synthesized in many tissues and has
      been shown to be associated with the development of obesity and metabolic
      disorders in animals and humans. The aim of this study is to investigate the
      relationship between serum NRG4 levels and various metabolic parameters in women
      with PCOS. This cross-sectional study included 40 women with PCOS and 40 age- and
      BMI-matched controls without PCOS. NRG4, fasting blood glucose (FBG), insulin, hs
      CRP, LDL-C, HDL-C, SHBG, DHEA-SO4 and total-testosterone levels were measured in
      all the participants. HOMA-IR was used to calculate the insulin resistance. Serum
      NRG4 levels were higher in women with PCOS than in healthy women (24.89 +/- 9.32
      [ng/mL] vs. 18.98 +/- 6.40 [ng/mL], p = 0.002). FBG, LDL-C, HDL-C, LH, SHBG, FAI,
      DHEA-SO4, insulin, hs-CRP, HOMA-IR and total-testosterone levels were
      significantly higher in women with PCOS than controls. Circulating NRG4 levels
      were positively correlated with HOMA-IR, insulin and hs-CRP for both groups.
      There was a positive correlation between NRG4 and FBG in the PCOS group. HOMA-IR
      and hs-CRP were associated with NRG4. The high concentration of circulating NRG4
      in PCOS may be associated with insulin resistance and low-grade chronic
      inflammation.

PMID- 29192412
TI  - Safety and efficacy of using advanced electrosurgical bipolar vessel sealing
      during vaginal hysterectomy in morbidly obese patients: a retrospective cohort
      analysis.
AB  - OBJECTIVES: To assess the safety and efficacy of electrosurgical bipolar vessel
      sealing during vaginal hysterectomy in morbidly obese patients MATERIAL AND
      METHODS: A total of 105 morbidly obese patients who underwent vaginal
      hysterectomy due to benign gynecologic pathologies between January 2010 and April
      2017 were included in the study. Patients were divided into two groups according
      to whether conventional suture ligation technique (n = 64) or electrosurgical
      bipolar vessel sealing (n = 41) were used during vaginal hysterectomy. The
      surgical procedure was performed with the same technique in both study groups.
      The primary outcomes were duration of surgery and estimated blood loss. The
      secondary outcomes were intra-operative complications and post-operative
      complications. RESULTS: The duration of surgery and estimated blood loss in the
      vessel sealing group was significantly less than in the conventional suture group
      (p < 0.05). No significant difference was present between the two groups in the
      rate of intra-operative and post-operative complications. CONCLUSIONS: The
      primary outcome of our study is that the EBVS system can be used equally and even
      more effectively in some aspects; and as safe an alternative approach to
      conventional suture ligation technique during vaginal hysterectomies performed
      specifically on morbidly obese patients with reduced operation times and blood
      loss, and without increasing the complication rates.

PMID- 29192413
TI  - Dysregulation of microRNAs in triple-negative breast cancer.
AB  - OBJECTIVES: Triple-negative breast cancer (TNBC) is an aggressive subtype of
      breast cancer with limited treatment options and poor prognosis. TNBC is usually
      diagnosed at a relatively young age and is characterized by high risk of
      developing metastases. Some epigenetic regulation of gene expression is
      associated with TNBC. Expression of microRNAs (miRNAs) can serve as a potential
      tool for identifying critical biomarkers in TNBC. The aim of our study is to
      examine expression of selected miRNAs in TNBC and to assess the relationship
      between miRNA expression and clinicopathological factors. MATERIAL AND METHODS:
      Expression levels of 19 selected miRNAs were compared between cancerous and
      normal breast tissues by use of qPCR method. We have evaluated the relationship
      between the expression level of miRNAs and clinicopathological factors such as:
      age, tumor size and lymph node status. RESULTS: We found that in TNBC tissues,
      when compared with normal breast tissues, the expression of miR-190a, miR- 136-5p
      and miR-126-5p was significantly reduced (p = 0.0041, p = 0.0007, p = 0.0007,
      respectively) whereas expression of miR-135b-5p and miR-182-5p was significantly
      increased (p = 0.0194, p = 0.0041, respectively). We found a linear trend for
      tumor size and expression of miR-126-5p (p = 0.0296) and miR-135b-5p (p =
      0.0241). CONCLUSIONS: Our study confirms that miRNA expression profile is
      dysregulated in TNBC patients compared to healthy controls. MiR-190a, miR-136-5p,
      miR-126-5p, miR-135b-5p and miR-182-5p may be associated with development and
      progression of TNBC.

PMID- 29192414
TI  - Outcomes of patients with advanced stage ovarian cancer with intestinal
      metastasis.
AB  - OBJECTIVES: The aim of this study is to evaluate the results of advanced stage
      (stage IIIB-IVB) ovarian cancer (OC) patients with intestinal metastasis, and to
      investigate the factors that affect survival. MATERIAL AND METHODS: Patients who
      underwent cytoreductive surgery (CS) for FIGO stage IIIB-IVB OC with metastasis
      in the intestinal system, at Tepecik Research and Treatment Hospital between 2008
      2014, were analyzed retrospectively. Patients with borderline ovarian tumor;
      those who had previously undergone radiation therapy and/or hysterectomy and
      patients having secondary or tertiary cytoreduction were excluded and 49 patients
      were included and analyzed in this study. Hysterectomy, bilateral salpingo
      oopherectomy, pelvic and para-aortic lymph node sampling, resection of bulky
      lymph nodes and omentectomy were performed. Optimal cytoreduction was accepted as
      that which left residual tumor <= one cm maximum size. RESULTS: The risk factors
      affecting OS interval were investigated according to Cox' regression analysis.
      Optimality of the primary CS (P = 0.008 and HR = 5.202) and cancer stage (P =
      0.016 and HR = 6.083) were found to be statistically significant factors.
      CONCLUSIONS: Achieving optimal CS is the most important aim for the general
      surgeon carrying out an intestinal resection procedure. Although resection
      procedures are superior in providing the desired optimal results when compared to
      excision surgery, their higher complication rates and subsequent lower quality of
      life must be taken into consideration when choosing either resection or excision
      methods; surgical intervention should always be kept to the minimum possible.

PMID- 29192415
TI  - DNA methyltransferase inhibitors influence on the DIRAS3 and STAT3 expression and
      in vitro migration of ovarian and breast cancer cells.
AB  - OBJECTIVES: Downregulation of DIRAS3 (DIRAS family, GTP-binding Ras-like 3) is
      related to ovarian and breast cancer progression. A possible mechanism that
      silences this gene is the promoter region DNA methylation. The potential
      reversibility of this epigenetic mechanism makes it more attractive candidate for
      new mode of cancer treatment. DIRAS3 regulates cell cycle, tumor dormancy and
      inhibits cancer cell growth and motility, all of which may indirectly depend on
      interaction with STAT3 (Signal Transducer and Activator of Transcription 3)
      classified as a potential oncogene. The restoration of DIRAS3 expression could
      inhibit cell proliferation and invasiveness. MATERIAL AND METHODS: Human ovarian
      carcinoma cell line (A2780) and human breast cancer cell line (MCF7) were exposed
      to two DNA methyltransferase inhibitors (DNMTi): decitabine (5-aza-2'
      deoxycytidine) [25 MUM and 12.5 MUM] and RG108 [150 MUM and 100 MUM]. In vitro
      migration changes of cancer cells were examined with wound healing assay. After 7
      days of DNMTi treatment cells were harvested and DNA and RNA was isolated. The
      methylation status of the promoter sequences of DIRAS3 and STAT3 genes was
      determined using methylation specific PCR (MS-PCR). Level of target genes'
      expression was quantified using quantitative reverse transcription PCR (QRT-PCR).
      RESULTS AND CONCLUSIONS: The in vitro wound healing assay showed changes in the
      migration rate of both adherent cell lines after DNMTi treatment compared to the
      untreated cells. Relative balance between methylated and unmethylated variants of
      DIRAS3 after MS-PCR was shifted towards unmethylated version after DNMTi
      treatment in A2780 cells. Statistically significant dose dependent effect of
      decitabine and RG108 on DIRAS3 expression in A2780 cells was observed.

PMID- 29192416
TI  - Mig-7 expression and vasculogenic mimicry in malignant ovarian tumors.
AB  - OBJECTIVES: To investigate the possible association of vasculogenic mimicry (VM),
      VE-cadherin and MIG-7 expression with clinicopathological features of women with
      malignant ovarian masses. MATERIAL AND METHODS: VM was studied with the PAS
      reaction and VE-cadherin was assessed with immunohistochemistry in 108 women with
      malignant ovarian tumors. Additionally, quantitative expression of MIG-7 mRNA was
      performed in 52 ovarian cancers with qRT-PCR. RESULTS: VM was found in 48/108
      cases (44%), more often in higher FIGO stage tumors (83% cases; 40 vs. 8; p =
      0.01). High expression of VE-cadherin was present in 37% of all ovarian masses.
      Ovarian tumors without VM more often expressed low levels of VE-cadherin than
      tumors where VM was found (37.6% vs.14.6%). No expression or very low expression
      of MIG-7 mRNA was found in all normal ovarian tissues and in 32 cancer samples.
      Median RQ of MIG-7 mRNA in tumor samples was higher than in normal ovarian tissue
      (RQ = 0.29 vs. RQ = 0.05, respectively; p < 0.005) and higher than in non
      malignant ovarian masses (0.98 vs. 0.05 respectively; p = 0.03). Expression of
      MIG-7 mRNA was significantly correlated with VM (p = 0.039). In tumors with PAS
      positive structures median RQ MIG-7 mRNA was higher than in tumors with PAS
      negative findings (1.89 vs. 0.13 respectively). VE-cadherin expression was more
      frequently found in tumors where MIG-7 mRNA was present (p = 0.004). CONCLUSIONS:
      Vasculogenic mimicry exists in malignant ovarian tumors and advanced clinical
      stages of malignancy are accompanied by a high incidence of VM formation. MIG-7
      mRNA and VE-cadherin expression may serve as additional molecular markers of VM
      in ovarian malignancies.

PMID- 29192417
TI  - Diagnostic hysteroscopy and the risk of malignant cells intraabdominal spread in
      women with endometrial cancer.
AB  - Although hysteroscopy is currently the undisputed gold standard for the
      examination of the uterine cavity in women with suspected endometrial cancer, it
      remains controversial as a procedure that can enhance metastasis spread.
      Endometrial cancer cells may shed during hysteroscopy and be passively
      transported with fluid flow into the peritoneal cavity. The paper presents the
      review of current knowledge regarding the risk of neoplasm metastases in women
      who had diagnostic hysteroscopy and the conditions that have to be met for the
      procedure to be safe. We searched PubMed, Ovid, Medline and Scopus databases for
      data published in the years 1985-2017. The following browsing criteria, the "MeSH
      headings": hysteroscopy, endometrial cancer, intraperitoneal or metastatic spread
      were used to find relevant papers. Based on the current data analysis we conclude
      that (1.) diagnostic hysteroscopy performed in women with endometrial cancer,
      especially in its early stages, is a very useful, efficient and safe diagnostic
      method and (2.) the distension media used for endoscopic procedures in the
      uterine cavity must be strictly controlled for relatively low pressures to
      prevent the increase in risk of endometrial cancer intraperitoneal spread.

PMID- 29192418
TI  - Novel biomarkers of overactive bladder syndrome.
AB  - The social aspect of overactive bladder syndrome (OAB) and the lack of objective
      diagnostic methods for this syndrome have spurred research into its potential
      biomarkers which can constitute useful diagnostic tools, while also allowing the
      evaluation of the intensity of clinical symptoms and the efficacy of implemented
      pharmacotherapy in OAB patients. Due to the complex etiopathogenesis of this
      syndrome, the researchers are seeking biomarkers connected with inflammation or
      nerve growth. The aim of this review was to analyse the latest literature data
      regarding potential biomarkers in OAB. The most promising opportunities are
      connected with the diagnostic use of the nerve growth factor (NGF), the brain
      derived neurotrophic factor (BDNF), C-reactive protein (CRP), prostaglandins and
      cytokines. Despite the most promising results to date having been obtained with
      regards to neurotrophic factors, it seems that, at the moment, none of these
      meets the criteria for becoming an isolated OAB marker. It is also suggested that
      the combined use of several biomarkers will facilitate obtaining the appropriate
      level of specificity and selectivity to allow their use in clinical practice.

PMID- 29192419
TI  - The course of pregnancy and delivery in a patient with malaria.
AB  - Malaria is one of the most common lethal parasitic diseases. Infection is
      transmitted when an infected female mosquito bites a human introducing the
      sporozoites into human blood. The article presents the course of pregnancy and
      delivery in a patient complicated by Plasmodium infection. The patient had
      repetitive several trips to Tanzania over a short time period before she
      developed the condition. She had been taking antimalarial medication (proguanil
      atovaquone) in a prophylactic dose during and after her first travel to Tanzania.
      Following her first return to Poland she experienced infection-related symptoms.

PMID- 29192420
TI  - Use of a levonorgestrel-releasing intrauterine device for menorrhagia treatment
      during adjuvant therapy of adrenocortical carcinoma with mitotane.
AB  - Adrenocortical carcinoma is a rare tumour with high malignancy and poor
      prognosis. This tumour is rarely diagnosed in the reproductive age. Complete
      surgical resection is the only curative treatment for adrenal cancer in all
      stages. After surgery adjuvant chemotherapy is required. Mitotane is the most
      important drug in adrenal cancer chemotherapy. Mitotane's mode of action is not
      entirely explained. Animal studies have shown that the substance exerts a direct
      cytotoxic effect on the cells of the adrenal cortex. This activity is selective,
      progressive and affects only the zona reticularis and fasciculata of the adrenal
      cortex. Mitotane inhibits cortisol synthesis by disrupting the chain of
      cholesterol. It has been suggested, that mitotane also affects the peripheral
      metabolism of steroids, especially of transcortin (CBG). This results in an
      increase of CBG blood concentration and a reduction of the amount of free
      hormones.

PMID- 29192421
TI  - The state of critical care ultrasound training in Europe: A survey of trainers
      and a comparison of available accreditation programmes.
AB  - BACKGROUND: Although critical care ultrasound (CCUS) in the Intensive Care Unit
      has been increasing exponentially for diagnostic and therapeutic purposes, the
      lack of a uniform formal training structure and programme has posed the question
      of whether scans have been appropriately performed or reported, and whether there
      exists proper clinical governance to ensure a high standard of care. METHODS: An
      online survey was sent to the representatives of various national intensive care
      societies via the European Society of Intensive Care Medicine CoBaTrICE
      committee. A comparison between 5 worldwide accreditation programmes was also
      made. RESULTS: Twenty-seven out of 42 countries replied our survey. Five
      countries had a nationally accredited programme in ICM Echocardiography while six
      were in the process of developing one. Three countries had a CCUS-accredited
      programme. Most had local programmes. Transthoracic echocardiography, lung and
      vascular ultrasound were considered essential. Although CCUS training programmes
      should incorporate a combination of theoretical and practical teaching, it is not
      clear which is the best format. The main barriers to delivering CCUS training
      included a lack of formally agreed competencies, as well as a lack of trainers
      and time. There is also a lack of agreement between the five accreditation
      programmes. CONCLUSIONS: There is a need for a well-structured and competent CCUS
      training program. The use of ultrasound in critical care for diagnostic and
      therapeutic purposes has been increasing exponentially. Once the remit of
      radiologists and cardiologists, point-of-care ultrasound and focused
      echocardiography is becoming an increasingly routine instrument for all acute
      specialties including intensive care medicine, despite the lack of evidence that
      it improves patient mortality in the ICU setting.

PMID- 29192422
TI  - Executive summary on the use of ultrasound in the critically ill: consensus
      report from the 3rd Course on Acute Care Ultrasound (CACU).
AB  - Over the past decades, ultrasound (US) has gained its place in the armamentarium
      of monitoring tools in the intensive care unit (ICU). Critical care
      ultrasonography (CCUS) is the combination of general CCUS (lung and pleural,
      abdominal, vascular) and CC echocardiography, allowing prompt assessment and
      diagnosis in combination with vascular access and therapeutic intervention. This
      review summarises the findings, challenges lessons from the 3rd Course on Acute
      Care Ultrasound (CACU) held in November 2015, Antwerp, Belgium. It covers the
      different modalities of CCUS; touching on the various aspects of training,
      clinical benefits and potential benefits. Despite the benefits of CCUS, numerous
      challenges remain, including the delivery of CCUS training to future
      intensivists. Some of these are discussed along with potential solutions from a
      number of national European professional societies. There is a need for an
      international agreed consensus on what modalities are necessary and how best to
      deliver training in CCUS.

PMID- 29192423
TI  - Bisphosphonates for Paget's disease of bone in adults.
AB  - BACKGROUND: Bisphosphonates are considered to be the treatment of choice for
      people with Paget's disease of bone. However, the effects of bisphosphonates on
      patient-centred outcomes have not been extensively studied. There are
      insufficient data to determine whether reducing and maintaining biochemical
      markers of bone turnover to within the normal range improves quality of life and
      reduces the risk of complications. OBJECTIVES: To assess the benefits and harms
      of bisphosphonates for adult patients with Paget's disease of bone. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, Embase, ISI Web of Knowledge and trials registers up to March
      2017. We searched regulatory agency published information for rare adverse
      events. SELECTION CRITERIA: Randomised controlled trials (RCTs) of
      bisphosphonates as treatment for Paget's disease in adults. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened search results, extracted
      data and assessed studies for risk of bias. We used standard methodological
      procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 20
      trials (25 reports, 3168 participants). Of these, 10 trials (801 participants)
      compared bisphosphonates (etidronate, tiludronate, ibandronate, pamidronate,
      olpadronate, alendronate, risedronate, zoledronate) versus placebo, seven
      compared two bisphosphonates (992 participants), one trial compared a
      bisphosphonates with a bisphosphonate plus calcitonin (44 participants), and two
      studies, the largest trial (1331 participants) and its interventional extension
      study (502 participants), compared symptomatic treatment and intensive treatment
      where the goal was to normalise alkaline phosphatase.Most studies were assessed
      at low or unclear risk of bias. Six of 10 studies comparing bisphosphonates
      versus placebo were assessed at high risk of bias, mainly around incomplete
      outcome data and selective outcome reporting.Participant populations were
      reasonably homogeneous in terms of age (mean age 66 to 74 years) and sex (51% to
      74% male). Most studies included participants who had elevated alkaline
      phosphatase levels whether or not bone pain was present. Mean follow-up was six
      months.Bisphosphonates versus placeboBisphosphonates tripled the proportion (31%
      versus 9%) of participants whose bone pain disappeared (RR 3.42, 95% confidence
      interval (CI) 1.31 to 8.90; 2 studies, 205 participants; NNT 5, 95% CI 1 to 31;
      moderate-quality evidence). This result is clinically important. Data were
      consistent when pain change was measured as any reduction (RR 1.97, 95% CI 1.29
      to 3.01; 7 studies, 481 participants).There was uncertainty about differences in
      incident fractures: 1.4% fractures occurred in the bisphosphonates group and none
      in the placebo group (RR 0.89, 95% CI 0.18 to 4.31; 4 studies, 356 participants;
      very low-quality evidence).None of the studies reported data on orthopaedic
      surgery, quality of life or hearing thresholds.Results regarding adverse effects
      and treatment discontinuation were uncertain. There was a 64% risk of mild
      gastrointestinal adverse events in intervention group participants and 48% in the
      control group (RR 1.32, 95% CI 0.91 to 1.92; 6 studies, 376 participants; low
      quality evidence). The likelihood of study participants discontinuing due to
      adverse effects was slightly higher in intervention group participants (4.4%)
      than the control group (4.1%) (RR 1.01, 95% CI 0.41 to 2.52; 6 studies, 517
      participants; low-quality evidence). Zoledronate was associated with an increased
      risk of transient fever or fatigue (RR 2.57, 95% CI 1.21 to 5.44; 1 study, 176
      participants; moderate-quality evidence).Bisphosphonates versus active
      comparatorMore participants reported pain relief with zoledronate than
      pamidronate (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 89 participants; NNT 5, 95%
      CI 3 to 11) or risedronate (RR 1.36, 95% CI 1.06 to 1.74; 1 study, 347
      participants; NNT 7, 95% CI 4 to 24; very low quality evidence). This result is
      clinically important.There was insufficient evidence to confirm or exclude
      differences in adverse effects of bisphosphonates (RR 1.05, 95% CI 0.95 to 1.76;
      2 studies, 437 participants; low-quality evidence) and treatment discontinuation
      (2 studies, 437 participants) (RR 2.04, 95% CI 0.43 to 9.59; 2 studies, 437
      participants; very low-quality evidence).Intensive versus symptomatic
      treatmentThere was no consistent evidence of difference to response in bone pain,
      bodily pain or quality of life in participants who received intensive versus
      symptomatic treatment.Inconclusive results were observed regarding fractures and
      orthopaedic procedures for intensive versus symptomatic treatment (intensive
      treatment for fracture: RR 1.84, 95% CI 0.76 to 4.44; absolute risk 8.1% versus
      5.2%; orthopaedic procedures: RR 1.58, 95% CI 0.80 to 3.11; absolute risk 5.6%
      versus 3.0%; 1 study, 502 participants; low-quality evidence).There was
      insufficient evidence to confirm or exclude an important difference in adverse
      effects between intensive and symptomatic treatment (RR 1.05, 95% CI 0.79 to
      1.41; low-quality evidence).There was insufficient evidence to confirm or exclude
      an important difference of risk of rare adverse events (including osteonecrosis
      of the jaw) from the regulatory agencies databases. AUTHORS' CONCLUSIONS: We
      found moderate-quality evidence that bisphosphonates improved pain in people with
      Paget's disease of bone when compared with placebo. We are uncertain about the
      results of head-to-head studies investigating bisphosphonates. We found
      insufficient evidence of benefit in terms of pain or quality of life from
      intensive treatment. Information about adverse effects was limited, but serious
      side effects were rare, and rate of withdrawals due to side effects was low.

PMID- 29192424
TI  - Interventions for Old World cutaneous leishmaniasis.
AB  - BACKGROUND: Cutaneous leishmaniasis, caused by a parasitic infection, is
      considered one of the most serious skin diseases in many low- and middle-income
      countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in
      Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly
      prescribed treatments are antimonials, but other drugs have been used with
      varying success. As OWCL tends to heal spontaneously, it is necessary to justify
      the use of systemic and topical treatments. This is an update of a Cochrane
      Review first published in 2008. OBJECTIVES: To assess the effects of therapeutic
      interventions for the localised form of Old World cutaneous leishmaniasis. SEARCH
      METHODS: We updated our searches of the following databases to November 2016: the
      Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also
      searched five trials registers and checked the reference lists of included
      studies for further references to relevant randomised controlled trials (RCTs).
      We wrote to national programme managers, general co-ordinators, directors,
      clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical
      companies, tropical medicine centres, and authors of relevant papers for further
      information about relevant unpublished and ongoing trials. We undertook a
      separate search for adverse effects of interventions for Old World cutaneous
      leishmaniasis in September 2015 using MEDLINE. SELECTION CRITERIA: Randomised
      controlled trials of either single or combination treatments in immunocompetent
      people with OWCL confirmed by smear, histology, culture, or polymerase chain
      reaction. The comparators were either no treatment, placebo/vehicle, and/or
      another active compound. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trials for inclusion and risk of bias and extracted data.
      We only synthesised data when we were able to identify at least two studies
      investigating similar treatments and reporting data amenable to pooling. We also
      recorded data about adverse effects from the corresponding search. MAIN RESULTS:
      We included 89 studies (of which 40 were new to this update) in 10,583 people
      with OWCL. The studies included were conducted mainly in the Far or Middle East
      at regional hospitals, local healthcare clinics, and skin disease research
      centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The
      overall mean age of participants was 25 years (range 12 to 56). Most studies
      lasted between two to six months, with the longest lasting two years; average
      duration was four months. Most studies were at unclear or high risk for most bias
      domains. A lack of blinding and reporting bias were present in almost 40% of
      studies. Two trials were at low risk of bias for all domains. Trials reported the
      causative species poorly.Here we provide results for the two main comparisons
      identified: itraconazole (200 mg for six to eight weeks) versus placebo; and
      paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus
      vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months'
      follow up, 85/125 participants in the itraconazole group achieved complete cure
      compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3
      studies; 244 participants). In one study, microbiological or histopathological
      cure of skin lesions only occurred in the itraconazole group after a mean follow
      up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However,
      although the analyses favour oral itraconazole for these outcomes, we cannot be
      confident in the results due to the very low certainty evidence. More side
      effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3
      studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53
      to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well
      as reports of headaches and dizziness), compared with the placebo group, but
      again we rated the certainty of evidence as very low so are unsure of the
      results.When comparing paromomycin with vehicle, there was no difference in the
      number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17;
      383 participants, 2 studies) and microbiological or histopathological cure of
      skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383
      participants, 2 studies), but the paromomycin group had more skin/local reactions
      (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI
      0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the
      certainty of evidence was very low, meaning we are unsure about these
      results.Trial authors did not report the percentage of lesions cured after the
      end of treatment or speed of healing for either of these key comparisons.
      AUTHORS' CONCLUSIONS: There was very low-certainty evidence to support the
      effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure
      (i.e. microbiological or histopathological cure and percentage of participants
      completely cured). Both of these interventions incited more adverse effects,
      which were mild in nature, than their comparisons, but we could draw no
      conclusions regarding safety due to the very low certainty of the evidence for
      this outcome.We downgraded the key outcomes in these two comparisons due to high
      risk of bias, inconsistency between the results, and imprecision. There is a need
      for large, well-designed international studies that evaluate long-term effects of
      current therapies and enable a reliable conclusion about treatments. Future
      trials should specify the species of leishmaniasis; trials on types caused by
      Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the
      effects of treating women of childbearing age, children, people with comorbid
      conditions, and those who are immunocompromised would also be helpful.It was
      difficult to evaluate the overall efficacy of any of the numerous treatments due
      to the variable treatment regimens examined and because RCTs evaluated different
      Leishmania species and took place in different geographical areas. Some outcomes
      we looked for but did not find were degree of functional and aesthetic
      impairment, change in ability to detect Leishmania, quality of life, and
      emergence of resistance. There were only limited data on prevention of scarring.

PMID- 29192425
TI  - Understanding the Current Status of Korean Heart Transplantation Based on Initial
      KOTRY Report.

PMID- 29192426
TI  - The Use Pattern and Clinical Impact of Novel P2Y12 Receptor Antagonists for Acute
      Myocardial Infarction in Korea.

PMID- 29192427
TI  - [Clinical application evaluation of Guidelines for Diagnosis and Treatment of
      Internal Diseases in Traditional Chinese Medicine].
AB  - To evaluate the applicability and clinical applications of Guidelines for
      Diagnosis and Treatment of Internal Diseases in Traditional Chinese Medicine, so
      as to provide the basis for the revision of the guidelines. This study was
      completed by the research and promotion base for traditional Chinese
      medicine(TCM) standard. The methods of applicability evaluation and application
      evaluation were used in the study. The questionnaires were filled out to evaluate
      applicability of the guideline, including doctor's familiarity with the
      guideline,the quality of the guideline, applicable conditions and clinical
      applications. The prospective case study analysis method was used to evaluate
      application of the guideline, including evaluation of clinical application
      compliance and application results(such as clinical effects, safety and economy).
      There were two parts in the guideline, which were TCM guideline and Western
      medicine guideline. The results of applicability evaluation showed that there
      were no obvious differences between TCM guideline and Western medicine guideline
      in doctor's familiarity with guideline(85.43%, 84.57%) and the use of the
      guideline(52.10%, 54.47%); the guidelines with good quality, and higher scores in
      the scope of application and the use of the term rationality(91.94%, 93.35%); the
      rationality scores of relevant contents in syndrome differentiation and treatment
      were more than 75%; the applicable conditions were better, and the safety score
      was the the highest. The comprehensive applicability evaluation showed that the
      proportion of the application of TCM guideline and Western medicine guideline
      were 77.73%, 75.46%, respectively. The results of application evaluation showed
      that there was high degree coincidence between the guideline with its clinical
      application; except for "other treatment" and "recuperation and prevention" in
      TCM, other items got high scores which were more than 90%; in the evaluation of
      application effects, safety of the guideline was best, economy of the guideline
      was better, and clincal effect was good. The comprehensive application evaluation
      showed that 75%~80% doctors were satisfied with the guideline. The Guidelines for
      Diagnosis and Treatment of Internal Diseases in Traditional Chinese Medicine has
      been widely used in clinical practice, which is of high quality, high degree of
      clinical application,good safety and economy. But there were some disadvantages
      of the guideline such as lack of evidence-based medicine and innovation, which is
      need to be improved constantly in the guideline revision.

PMID- 29192428
TI  - [Clinical application evaluation of Guidelines for the Diagnosis and Treatment of
      Common Diseases of Pediatrics in Traditional Chinese Medicine].
AB  - Clinical application evaluation research of Guidelines for the Diagnosis and
      Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine
      intends to evaluate the quality level and clinical application of the guideline.
      A questionnaire and prospective case survey methods were used to evaluate the
      applicability evaluation based on the clinician questionnaire and the application
      evaluation based on clinical case observation. The applicability evaluation,
      familiarity and utilization rate of doctors' guidelines were 85.06%, 62.76%; Sort
      by technical grade, intermediate grade doctors have a higher familiarity rate and
      utilization rate, while the junior grade doctor's is lower; Guide quality level
      of applicability evaluation, other items' rational percentage are better than 96%
      except the items of health preserving and prevention and other treatment is
      relatively low; Items' applicable percentage of applicability evaluation are more
      than 91% except the item of guide simplicity. Comprehensive applicability
      evaluation, The percentage of the guideline applicable to clinical practice
      accounted for 94.94%. The consistency rate of syndrome differentiation and
      clinical application is more than 96% in addition to prescription medication,
      other treatments and health preserving and prevention of the guidelines apply
      consistency of application evaluation. The percentage of good treatment effect
      accounted for 92.96% of application effect evaluation. The safety percentage is
      99.89% and economy is 97.45%. The research shows that of Guidelines for the
      Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese
      Medicine quality level is good and is basically applicable to pediatric clinical
      practice which can be used as a standardized recommendation of pediatric common
      diseases' treatment specification. A small part of the guidelines are not
      applicable and need to be further consummated. Health preserving and prevention
      and other treatment of the guideline need to be revised.

PMID- 29192429
TI  - [Clinical application evaluation of Guidelines for Diagnosis and Treatment of
      Common Diseases of Otolaryngology in Traditional Chinese Medicine].
AB  - This study is to assess the Guidelines for Diagnosis and Treatment of Common
      Diseases of Otolaryngology in Traditional Chinese Medicine in clinical
      application and provide evidence for further guideline revision. The assessment
      was divided into applicability assessment and practicability assessment. The
      applicability assessment based on questionnaire survey and the traditional
      Chinese medicine (TCM) practitioners were asked to independently fill the
      Questionnaire for Applicability Assessment on the Guidelines for Diagnosis and
      Treatment in Traditional Chinese Medicine. The practicability assessment was
      based on prospective case investigation and analysis method and the TCM
      practitioners-in-charge filled the Case Investigation Questionnaire for
      Practicability Assessment on the Guidelines for Diagnosis and Treatment in
      Traditional Chinese Medicine. The data were analyzed in descriptive statistics.
      151 questionnaires were investigated for applicability assessment and 1 016
      patients were included for practicability assessment. The results showed that
      88.74% of them were familiar with the guidelines and 45.70% used them. The
      guidelines quality and related items were similar in applicability assessment and
      practicability assessment, and scored highly as more than 85.00% except the
      "recuperating and prevention". The results suggested that the quality of
      Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in
      Traditional Chinese Medicine was high and could better guide the clinical
      practice. The "recuperating and prevention" part should be improved and the
      evidence data should be included in future guideline revision, so that the
      clinical utilization rate could be increased.

PMID- 29192430
TI  - [Clinical application evaluation of Guidelines for Diagnosis and Treatment of
      Cancer in Traditional Chinese Medicine].
AB  - This study aims to evaluate the adaptability and applicability of Guidelines for
      the Diagnosis and Treatment of Cancer in Traditional Chinese Medicine. The
      assessment methods included adaptability assessment and applicability assessment.
      The adaptability assessment was based on the questionnaire survey to evaluate the
      familiarity, utilization, quality, and clinical application of the Guidelines;
      applicability assessment was based on the prospective observation of 853 clinical
      cases to investigate the applicability and effect of the Guidelines, including
      effectiveness, economy and safety. Statistical analysis for basic description,
      construction of different comparison groups for cross or hierarchical statistical
      test, multi-factor analysis, and confounding factors were used in the study.
      Adaptability assessment results showed that 63.03% of TCM doctors considered
      guidelines as good or very good applicability and 4.24% of TCM doctors considered
      guidelines with very poor applicability in clinical practice. For the
      applicability evaluation, TCM doctors considered that the "overall efficacy and
      technology level", "satisfactory degree" and "adaptability in clinical practice"
      of the guideline were 85.46%, 80.43% and 69.40% respectively. The results showed
      that guideline was well known among TCM doctors, especially junior TCM doctors.
      Adaptability and applicability of Guidelines were totally good but the quality
      and adaptability of the intervention schemes were still week, so the quality of
      Guidelines should be improved by revision.

PMID- 29192431
TI  - [Clinical application evaluation of Guidelines for Diagnosis and Treatment of
      Common Diseases of Coloproctology in Traditional Chinese Medicine].
AB  - To provide reference for revising the Guidelines for Diagnosis and Treatment of
      Common Diseases of Coloproctology in Traditional Chinese Medicine (TCM) through
      clinical research. 9 TCM hospitals worldwide have conducted a survey and
      questionnaires for 7 CPGs have been received. 263 cases clinical doctors accepted
      the applicability survey of guidelines. 89.35% is more familiar to the guidelines
      and 36.12% have been used the guidelines. In syndrome differentiation and
      treatment related contents, diagnostic point, treatment and syndrome
      differentiation are higher, accounted for 96.96%, 88.59%, 96.20%, respectively.
      Rationality of prevention is lower, accounted for 65.02%.88.21% clinical doctors
      believe that the Guidelines for Diagnosis and Treatment of Common Diseases of
      Coloproctology in Traditional Chinese Medicine is applicable. The application of
      the guidelines is evaluated by prospective observation of 1 309 cases. The higher
      consistency between guidelines and clinical practice is Western medicine disease
      diagnosis and traditional Chinese medicine disease diagnosis, accounted for
      98.70%, 90.76%, respectively. The lower is rationality of prevention, accounted
      for 49.27%. The safety and economy of the guidelines are better, accounted for
      97.02%, 95.11%, respectively. The comprehensive evaluation results showed that
      the overall treatment effect and technical level, satisfaction degree,
      applicability in clinical practice which were 7-9 points is 81.52%, 80.60%,
      79.30%.The complex evaluation of diagnosis and treatment of common diseases of
      coloproctology in TCM guidelines is good, and suitable for clinical application
      with increase the content of rationality of prevention.

PMID- 29192432
TI  - [Clinical application evaluation of Guidelines for Diagnosis and Treatment of
      Common Diseases of Dermatology in Traditional Chinese Medicine].
AB  - To assess the quality and application effect of Guidelines for Diagnosis and
      Treatment of Common Diseases of Dermatology in Traditional Chinese
      Medicine(Guidelines) through the applicability and applicability evaluation
      respectively. The questionnaire survey was adopted to evaluate the applicability
      of the Guidelines, including the utilization, quality, and clinical application
      conditions. The results showed that the familiarity rate and utilization rate of
      the Guidelines were 85.37%, 48.78%, respectively. The data showed that the
      familiarity and the utilization rates were different in the working staff with
      different professional titles. The evaluation level was the lowest given by the
      staff with junior professional title (70.97%, 29.03%) in comparison. The
      assessment showed the overall quality of the Guideline was good and slightly low
      level for the rationality scores of the other therapeutic methods as well as for
      the recuperation and prevention (80.49%, 85.37%), which was in line with the
      clinical compliance of the Guideline. The perspective observation of clinical
      cases was used for the applicability evaluation, including clinical compliance of
      the Guideline, effect evaluation, and comprehensive assessment, et al. The
      results showed that the safety score was the highest, followed by the economic
      issue and efficacy. For the comprehensive evaluation of the applicability,
      complete applicability accounted for 29.27%, and the general applicability
      accounted for 87.80%. It was showed in the three index scores of the
      applicability evaluation that the accumulative score 7-9 scores were 75.65%,
      73.89%, 71.12%. Through the applicability and applicability evaluation, the
      Guideline was satisfactory in the overall quality, high in the safety of clinical
      application and good in efficacy and economic issues. There are some limits on
      the development method and technical issues in the Guideline, which is required
      to be supplemented in the revision. Additionally, the strategy study on the
      promotion of the Guideline should be enhanced so as to expedite the recognition
      and utilization of the Guideline.

PMID- 29192433
TI  - [Clinical application evaluation of Guidelines for Diagnosis and Treatment of
      Common Diseases of Gynecology in Traditional Chinese Medicine].
AB  - To evaluate the clinical applicability and application of Guidelines for
      Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese
      Medicine, 11 diseases from Guidelines for Diagnosis and Treatment of Common
      Diseases of Gynecology in Traditional Chinese Medicine were evaluated by methods
      of questionnaire and prospective case study at 16 construction units for
      traditional Chinese medicine standards research and extension. Results showed
      that 361 clinical doctors accepted the applicability survey of guidelines, and
      87.26% of them were more familiar to the guideline and 25.21% of them used the
      guideline. In syndrome differentiation and treatment related contents,
      rationality of prescription medication and syndrome classification was higher,
      accounted for 91.69% and 86.98% respectively, but the rationality of recuperation
      prevention was lower, accounted for 44.6%. 75.62% clinical doctors believed that
      the Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in
      Traditional Chinese Medicine was applicable. The application of the guidelines is
      evaluated by prospective observation of 2 935 cases. The higher compliance
      between the guideline and clinical practice was present in TCM (traditional
      Chinese medicine) disease diagnosis and WM (western medicine) disease diagnosis,
      accounted for 98.30% and 94.11% respectively. The lower compliance was present in
      recuperation prevention, accounted for 59.39%. The safety and economy of the
      guideline was higher, accounting for 95.64%, 94.75%, respectively. The
      comprehensive evaluation results showed that the rate of the overall treatment
      effect with technical level, satisfaction degree or applicability in clinical
      practice which were 7-9 points is 77.38%, 74.00%, 76.90% respectively. This
      guideline has a high clinical compliance and can be used as a standard for common
      diseases of gynecology, but there are also some conditions with poor
      applicability, which does not conform to the actual situation, and needs to be
      further revised.

PMID- 29192434
TI  - [Research on technology regulation of non-polluted cultivation and strategies of
      Panax ginseng cultivation in farmland].
AB  - As the limit of the usage of available forest land, cultivated ginseng in the
      farmland would become the mainly Panax ginseng planting mode, meanwhile the non
      polluted production technology would be the mainly development direction in the
      future. In this study, the non-polluted cultivation technology system of P.
      ginseng was established based on the research results of field investigation in
      the cultivated regions. The system includes suitable planting regions selecting,
      planting method, field management, pest control, harvesting & processing, and
      quality control. Aimed at the serious issues in the cultivation, research
      strategies have been provided to guarantee the sustainable development of the
      ginseng industry. The patterns of soil restoration after P. ginseng cultivation,
      establishment the platform of comprehensive disease & pest control, breeding new
      varieties for high stress tolerance and resistance, and a traceability system for
      P. ginseng cultivation. In all, these strategies was considered to largely
      developing of the ginseng industry in the green and sustainable way.

PMID- 29192435
TI  - [Discussion on scientific problems in standard decoction of traditional Chinese
      medicine].
AB  - Based on the reviewing of development and disadvantages of Chinese medicine
      formula granules, the concept of standard decoction of traditional Chinese
      medicine was proposed in this study, and it was used as the standard mode of
      Chinese medicine formula granules to standardize the production process and
      quality standards of formula granules. The standard was unified according to the
      principles of "standardization of medicinal materials, standardization of
      process, intellectualization of production, standardization of quality,
      normalization of packaging, and informatization of storage"; and consistency
      evaluation was carried out by the analysis of chemical components,
      pharmacological activities and clinical efficacy of the standardized decoction
      and the traditional decoction, interpreting the scientific questions to ensure
      the stability and uniformity of Chinese medicine formula granule as well as the
      safety and effectiveness of its clinical application.

PMID- 29192436
TI  - [Advances in research on relationships among Lycium species and origin of
      cultivated Lycium in China].
AB  - The Lycium genus consists of consist of 7 species and 3 variety which are main
      distributed in Northwest region in China, the cultivated Goji berry appeared
      about 1 000 years ago. The phylogeny of the wild Goji berry and the domestication
      of cultivated Goji berry are important scientific and practical value due to the
      medicinal and economic value. In this paper, a new advances achieved in studies
      on the phylogeny of wild Goji berry is summarized. The origin of cultivated Goji
      berry includes when, where, how and ancestral specie were reviewed. The current
      situation of cultivation and existing problems were summarized. We considered
      that through mutations and artificial selections, wild ancestors were
      domesticated to current cultivar groups. To find direct evidence for the origin
      of cultivated Goji berry, we must rely on genetic analysis in addition to
      morphological characters. To make full use of the Goji berry germplasm resources,
      the investigation and mining on wild Goji berry resource should be strengthened
      in the future.

PMID- 29192437
TI  - [Summary and prospect of medicinal plant active substances in regulation of p65
      nuclear translocation].
AB  - As the most important nuclear transcription factors in the cells, NF-kappaB is
      involved in many intracellular signaling pathways and transcription and
      regulation of genetic information. The signal transduction pathways mainly
      include the activation of IkappaB kinase, degradation of IkappaB protein and the
      nuclear translocation of p65. p65 trans-nuclear binding with DNA is the key for
      NF-kappaB to play a role. Abnormal activation of NF-kappaB is a major factor in
      the induction of oxidative stress, inflammation, cancer and so on. Therefore,
      maintaining the balance of NF-kappaB activity and regulating the nuclear
      translocation of p65 have great significance for further research on related
      subjects. In this paper, the regulation effects of the main active substances of
      medicinal plants (such as polyphenols, saponins, and alkaloids) on p65 nuclear
      translocation and the upstream pathway of NF-kappaB were discussed, expecting to
      provide reference for the development of natural active substances for functional
      food.

PMID- 29192438
TI  - [Research progress on medicinal values of scorpion venom components].
AB  - For thousands of years, scorpions and their venoms have been applied in
      traditional medicine in China to treat a variety of difficult miscellaneous
      diseases. The venom is a complex mixture of bioactive molecules, such as peptides
      and proteins (e.g. neurotoxins). Among them, neurotoxins (named scorpion toxins)
      are the most important bioactive components. Up to now, more and more
      characterized venom components have been isolated from different scorpions,
      providing numerous candidate molecules for drug design and development. Many
      investigations have shown the potent effects of venom or its components against
      the nervous, immune, infection, cardiovascular and neoplastic diseases. Moreover,
      the scorpion toxins could be used as molecular backbone to develop new specific
      drugs based on their unique structures and functions. In this review, we focus on
      the medicinal values and the possible mechanisms of scorpion toxins with
      promising medicinal prospect against the relative diseases, providing the data
      basis for further development of relative drugs.

PMID- 29192439
TI  - [Cloning and expression analysis of transcription factor AsMYB1 and AsMYB2 from
      Aquilaria sinensis].
AB  - The MYB gene family comprises one of the richest groups of transcription factors
      in plants. The full length of two MYB genes were isolated through heterologous
      screening of Aquilaria sinensis calli transcriptome data, and the reverse
      transcription PCR was performed to obstain the corrected MYB clones, named
      AsMYB1, AsMYB2. The MYB transmembrane domain and phylogenetic analysis were
      predicted by different software to analyze the bioinformatics of MYB proteins.
      The transcript level of AsMYB1, AsMYB2 was performed by real-time quantitative RT
      PCR in different tissues and in responds to abiotic stresses including salt,
      cold, metal and drought stress, and hormone treatments including abscisic acid
      (ABA), salicylic acid (SA), gibberellins (GA3) and methyl jasmonate (MeJA)
      treatment. The AsMYB1 cDNA sequence had an ORF of 1 063 nucleotides, encoding a
      protein of 353 amino acids. The largest AsMYB2 ORF was 1 081 nucleotides, and its
      predicted translation products consisted of 359 amino acids. Two MYB genes had a
      tissues-specific pattern in A. sinensis. Moreover, the expression level of AsMYB1
      and AsMYB2 was regulated by different abiotic stresses and hormone treatments,
      suggesting the transcription factors AsMYB1 and AsMYB2 play an important role in
      plant defense and hormone signal transduction in A. sinensis.

PMID- 29192440
TI  - [Effect of nitrogen, phosphorus and potassium fertilizers on Flos Sophorae
      Immaturus yield and quality in hilly area of Chongqing].
AB  - With Sophora japonica at the flowering stage as the object, the effect of
      nitrogen, phosphorus and potassium fertilizers on the yield composition factors,
      yield and quality of Flos Sophorae Immaturus (FSI) was studied. The results
      indicated that in early spring, nitrogen, phosphorus and potassium fertilizer on
      the amplification rate of S. japonica, FSI yield composition, yield and quality
      were different significantly, middle to high nitrogen (1.5-2.0 kg/plant)
      significantly increased the level of panicled clusters, raceme and flower bud
      number and yield. Phosphorus (1.5-2.0 kg/plant) could significantly increase the
      total buds of flower number and yield, potassium showed no significant increase
      in yield and yield components. Comprehensively considering yield and quality of
      FSI, nitrogen 1.5-2.0 kg/plant, phosphorus 1.5-2.0 kg/plant and potassium 0.6-0.9
      kg/plant are appropriate.

PMID- 29192441
TI  - [Studies on identification of Phragmitis Rhizoma and its counterfeits].
AB  - The study aims to explore the main differential characteristics of Phragmites
      Rhizoma and its counterfeits (rhizomes of Arundo donax, Triarrhena lutarioriparia
      and Miscanthus sinensis) and provide experimental basis for the reasonable
      applications of gramineous plants through system research and comparison of plant
      morphogenesis, character, transverse organization characteristics and powder
      microscopic characteristics.

PMID- 29192442
TI  - [Study of heterologous efficient synthesis of cucurbitadienol].
AB  - Cucurbitadienol has anti-inflammation, anti-cancer activities, and acts as a
      precursor of traditional Chinese medicine active ingredients mogroside and
      cucurbitacine. For construction of a Sacchromyces cerevisiae cell factory for
      production of cucurbitadienol, we firstly cloned a cucurbitadienol synthase (CBS)
      gene from Siraitia grosvenorii. Then, through heterologous expression of CBS in
      the triterpenoid chassis strain WD-2091, the engineered strain could produced
      27.44 mg*L -1 cucurbitadienol, which was determined by GC-MS. Further regulation
      of CBS expression led to cucurbitadienol's titer increasing by 202.07% and
      reaching 82.89 mg*L -1 in the shake flask fermentation and 1 724.10 mg*L -1 in
      the high cell density fermentation. Our research promotes the cucurbitane-type
      tetracyclic triterpenoids synthesis pathway analysis progress and provides the
      basis for further obtaining cell factories for production of cucurbitadienol
      tetracyclic triterpenoids.

PMID- 29192443
TI  - [EST-SSR identification, markers development of Ligusticum chuanxiong based on
      Ligusticum chuanxiong transcriptome sequences].
AB  - Ligusticum chuanxiong is a well-known traditional Chinese medicine plant. The
      study on its molecular markers development and germplasm resources is very
      important. In this study, we obtained 24 422 unigenes by assembling transcriptome
      sequencing reads of L. chuanxiong root. EST-SSR was detected and 4 073 SSR loci
      were identified. EST-SSR distribution and characteristic analysis results showed
      that the mono-nucleotide repeats were the main repeat types, accounting for
      41.0%. In addition, the sequences containing SSR were functionally annotated in
      Gene Ontology (GO) and KEGG pathway and were assigned to 49 GO categories, 242
      KEGG pathways, among them 2 201 sequences were annotated against Nr database. By
      validating 235 EST-SSRs,74 primer pairs were ultimately proved to have high
      quality amplification. Subsequently, genetic diversity analysis, UPGMA cluster
      analysis, PCoA analysis and population structure analysis of 34 L. chuanxiong
      germplasm resources were carried out with 74 primer pairs. In both UPGMA tree and
      PCoA results, L. chuanxiong resources were clustered into two groups, which are
      believed to be partial related to their geographical distribution. In this study,
      EST-SSRs in L. chuanxiong was firstly identified, and newly developed molecular
      markers would contribute significantly to further genetic diversity study, the
      purity detection, gene mapping, and molecular breeding.

PMID- 29192444
TI  - [Wetting agent dosage screening for traditional Chinese medicine pellet based on
      torque rheological property].
AB  - With lubricant and bonding effect simultaneously, wetting agent has direct effect
      on properties of wet mass and extrudate, thus affecting the forming quality of
      pellets in extrusion-spheronization process. In this research, 25 representative
      kinds of traditional Chinese medicine(TCM) were selected as model drugs and 20%,
      30% and 40% drug loading were set with MCC as their balling agent. The torque
      rheological curves were measured to get parameters such as maximum torque (Tmax)
      and corresponding water addition (WTmax) for these 75 raw materials by a mixer
      torque rheometer (MTR).The results showed that among 75 representative raw
      materials, 74 ones could be obtained for spherical pellets under the water
      addition of WTmax-2. corresponding to the second largest torque in torque
      rheological curve, suggesting that MTR could be used to select the optimal
      wetting agent dosage of TCM pellets. So the tedious and expensive pre-production
      work could be considerably reduced when TCM pellets were prepared.

PMID- 29192445
TI  - [Effects of Frankincense and Myrrh essential oil on transdermal absorption of
      ferulic acid in Chuanxiong].
AB  - The aim of this paper was to explore the effects of Frankincense and Myrrh
      essential oil on transdermal absorption, and investigate the mechanism of
      permeation on the microstructure and molecular structure of stratum corneum.
      Through the determination of stratum corneum/medium partition coefficient of
      ferulicacid in Chuanxiong influenced by Frankincense and Myrrh essential oil, the
      effects of volatile oil of frankincense and Myrrh on the the microscopic and
      molecular structure of stratum corneum were explored by observation of skin
      stratum corneum structure under scanning electron microscopy, and investigation
      of frankincense and myrrh essential oil effects on the molecular structure of
      keratin and lipids in stratum corneum under Fourier transform infrared
      spectroscopy. The results showed that the oil could enhance the distribution of
      ferulic acid in the stratum corneum and medium, and to a certain extent damaged
      the imbricate structure of stratum corneum which was originally regularly,
      neatly, and closely arranged; some epidermal scales turned upward, with local
      peeling phenomenon. In addition, frankincense and myrrh essential oil caused the
      relative displacement of CH2 stretching vibration peak of stratum corneum lipids
      and amide stretching vibration peak of stratum corneum keratin, indicating that
      frankincense and myrrh essential oil may change the conformation of lipid and
      keratin in the stratum corneum, increase the bilayer liquidity of the stratum
      corneum lipid, and change the orderly and compact structure to increase the skin
      permeability and reduce the effect of barrier function. It can be concluded that
      Frankincense and Myrrh essential oil can promote the permeation effect by
      increasing the distribution of drugs in the stratum corneum and changing the
      structure of the stratum corneum.

PMID- 29192446
TI  - [Grades evaluation of Phellodendri chinensis cortex pieces based on quality
      constant].
AB  - Quality constant is a comprehensive grades evaluation method for traditional
      Chinese medicine decoction pieces, which is better but based on traditional way.
      In this paper, a new grading mode for Phellodendri chinensis pieces was
      established based on quality constant evaluation method. The results showed that
      the range of relative quality constant for 15 batches of different samples was
      from 0.41 to 0.96. As customary, if these samples were divided into three grades:
      the relative quality constant shall be >=0.77 for first grade; <0.77 but >=0.48
      for the second grade; and <0.48 for the third grade. This research indicated that
      the quality constant mode can be used to effectively grade the P. chinensis
      pieces in a scientific, reasonable, objective and specific way. Simultaneously,
      it provided a beneficial reference for grading cortex herbal pieces or medicines.

PMID- 29192447
TI  - [HUVECs extraction and UHPLC LTQ Orbitrap analysis for screening vascular
      endothelium protective components in Kudiezi injection].
AB  - An effective method has been employed as a tool for screening active components
      in Kudiezi injection by using cell chromatography and sensitive UHPLC-HR-MSn
      method. The potential bioactive components in Kudiezi injection could be
      selectively bound to the HUVECs target cells first. After cell target
      desensitization and inactivation, the chemical constituents with cell target
      affinity were identified by LC-MS, so as to screen the possible active components
      in Kudiezi injection. Based on the accurate mass measurements and the retention
      time, in total, 9 compounds were tentatively identified and characterized,
      including 4 sesquiterpene lactones, 3 phenolic acids and 2 flavonoids. HUVECs
      biospecific extraction coupled with UHPLC-LTQ-Orbitrap analysis could provide a
      rapid and efficient method for the identification of potential bioactive
      components in Kudiezi injection, and provide the reference for further research
      on its effective materials basis.

PMID- 29192448
TI  - [Simultaneous determination of six triterpenoid acids from Guizhi Fuling capsules
      by UPLC-MS/MS].
AB  - To establish a UPLC-MS/MS method for simultaneous determination of six
      triterpenoid constituents (pachymic acid, dehydropachymic acid, dehydrotumulosic
      acid, polyporenic acid C, dehydroeburicoic acid and dehydrotra metenolic acid) in
      Guizhi Fuling capsules (GFC). Chromatographic analysis was conducted on Agilent
      Porosheell 120 SB-C18 column (4.6 mm*150 mm, 2.7 MUm), with 0.1% formic acid
      aqueous solution-methanol as the mobile phase for gradient elution at a flow rate
      of 0.4 mL*min-1. The column temperature was 30 C and the sample size was 5 MUL.
      The samples were analyzed by tandem mass spectrometer with negative electrospray
      ionization (ESI) source, and monitored under a multiple reaction monitoring (MRM)
      mode, with the quantitative ion pairs m/z 527.8->465.5 (pachymic acid), m/z 525.6
      >465.6 (dehydropachymic acid), m/z 483.4->337.3 (dehydrotumulosic acid), m/z
      481.5->419.5 (polyporenic acid C), m/z 467.4->337.1 (dehydroeburicoic acid), m/z
      453.4->337.0 (dehydrotra metenolic acid). Six triterpenoid acids showed good
      linear relationships within the investigated concentration ranges (r> 0.996 8),
      with RSDs of precision less than 6.2%, and all RSDs of repeatability less than
      5.9%. The average recovery rate was 97.90%, 100.2%, 99.60%, 101.7%, 102.6% and
      103.0% respectively. The method was rapid, accurate, repeatable and could be used
      as a method for quantitative determination of triterpenoid acids in Chinese
      medicine prescriptions, providing a reference method for the quality control of
      Guizhi Fuling capsules and providing a reference for the content determination
      for Chinese medicine prescriptions containing Poria cocos.

PMID- 29192449
TI  - [Study on metabolites from a sponge-derived fungus].
AB  - We have carried out the investigation on a sponge-derived fungus,which was
      identified as Emericella variecolor from the south sea of China. Two new chemical
      constituents,(+)-2-acetyl-dihydroterrein (1) and (+)-3-acetyl-dihydroterrein
      (2),with four known compounds,anditomin (3),andilesin A (4),andilesin C (5) and
      andilesin B (6),were isolated from this fungus by column chromatography over
      silica gel, Sephadex LH-20, and ODS. The structures of 1 and 2 were elucidated by
      spectroscopic methods including NMR,HR-ESI-MS,and CD.

PMID- 29192450
TI  - [Chemical constituents from roots of Stelleropsis tianschanica].
AB  - The constituents from 95% ethanol extract of the roots of Stelleropsis
      tianschanica were purified by column chromatography techniques, leading to the
      isolation of 17 compounds. Their structures were elucidated by spectroscopic
      dataas 5'-methoxy lariciresinol(1), pinoresinol(2), daphnoretin(3),
      acutissimalignan B(4),(+)-secoisolariciresinol(5),(+)-epipinoresinol(6), 7-methyi
      daphnoretin(7), thero-8S-7-methoxysyringylglycerol(8), 1-O-methyl
      guaiacylglycerol(9), 2R-22'-ferulic acid ester-2,3-dihydroxypropyl ester(10),
      vesiculosin(11), 4beta,5betaH-guai-9,7(11)-dien-12,8-olide-1alpha,8alpha
      diol(12),(-)-nortrachelogenin(13), 4alpha,5betaH-guai-9,7(11)-dien-12,8-olide
      1alpha,8alpha-diol(14), matairesinol(15), lariciresinol(16)and
      isolariciresinol(17). Among them, compounds 1-13 wereobtained for the first time
      fromthe genus Stelleropsis. Compounds 3, 7, 10-14 were tested for their
      activation of orphan nuclear receptor TR3 with the immunofluorescence technology
      in 50 MUmol*L-1. The results showed that compound 10 displayed moderate activity
      with the activity ratio of 76.38%, and the others were only about 50.0%.

PMID- 29192451
TI  - [Study on naphthopyrone reference extract and application on assay of Semen
      Cassiae].
AB  - A quality control method of Semen Cassiae was established by using naphthopyrone
      reference extract(NRE). Meanwhile, the feasibility about NRE replacing single
      component reference in quality control of traditional Chinese medicine was
      explored. After NRE of Semen Cassiae being prepared by chromatographic separation
      technology, we determined the three main components, cassiaside B2, rubrofusarin
      6-O-beta-D-gentiobioside and cassiaside C. In the meantime, an HPLC analytical
      method, based on the NRE as standard substance, was developed to determinate the
      contents of three main components in Semen Cassiae. T-test was used for
      comparison of the determination results of the two methods(single chemical
      component and NRE as reference substances, respectively), and the T-test result
      demonstrated that there was no significant difference between the two methods.
      The results developed scientific basis for the application of NRE of Semen Cassia
      in the quality control, which could be applied for the quality control of
      traditional Chinese medicine using reference extract substituting single chemical
      reference, and provide a new research model for the quality control of Chinese
      medicine.

PMID- 29192452
TI  - [Analysis on quality and differences of Mentha haplocalyx from different
      regions].
AB  - A gas chromatography-mass spectrometry(GC-MS)method was established for the
      analysis of volatile components in Mentha haplocalyx, and seven principal
      components were quantified by gas chromatography(GC). Based on these analyses,
      the differences of volatile components in M. haplocalyx from Jiangsu, Anhui and
      other regions were compared. The results showed that the volatile oil of M.
      haplocalyx was divided into four chemical types:menthol-menthone type, pulegone
      menthone type, piperitone-menthol type, piperitone epoxide type, and menthol
      menthone type was the principal type. Menthol was the highest and pulegone was
      the lowest. The differences of M. haplocalyx from Anhui and other regions were
      obvious. The major volatile components and the differences of M. haplocalyx from
      different regions were confirmed and a quantitative method was established for
      the determination of volatile components, which provided the basis for improving
      the quality standard of M. haplocalyx.

PMID- 29192453
TI  - [Removal of lipopolysaccharides from anti-complementary crude polysaccharides of
      Houttuynia Herba].
AB  - An Affi-Prep Polymyxin column was combined with a Phenyl Sepharose column and a
      Sephacryl S-300 column, respectively, to remove the lipopolysaccharides(LPS) in
      the anti-complementary crude polysaccharides of Houttuynia Herba. The contents of
      LPS in the polysaccharides were determined by chromogenic tachypleus amebocyte
      lysate(TAL)method during the procedure of purifying. The anti-complementary
      activities of the polysaccharides were also compared before and after the removal
      of LPS. Less remanent LPS was detected after purified using Penyl Sepharose
      combined with polymyxin column, with the clearance rate of 42.85%. All the
      columns had no effect on the anti-complementary activity of the polysaccharides.
      Penyl Sepharose combined with polymyxin column would be sound for LPS removal of
      the anti-complementary polysaccharides without reducing their bioactivity.

PMID- 29192454
TI  - [Rapid prediction of the content of polyphyllin in various species of Paris by
      infrared spectrometry].
AB  - Polyphyllin is the main active constituent in Paris which was a traditional
      Chinese medicine. In order to evaluate the quality of Paris rapidly and ensure
      the efficacy in clinical therapy, we quantified the contents of polyphyllin I,
      polyphyllin II and polyphyllin VII using infrared spectroscopy with partial least
      squares regression(PLSR). The method for evaluating the quality of Paris was
      established. Infrared spectra of 78 samples from various species in different
      origins were collected. The contents of polyphyllin I, II and VII were determined
      by high performance liquid chromatography(HPLC). The HPLC data were combined with
      the spectral data to predict the contents of three polyphyllin rapidly.
      Multiplicative signal correction(MSC), standard normal variate(SNV), orthogonal
      signal correction(OSC), first derivative and second derivative were utilized for
      the spectral preprocessing. Then, the optimized spectral data were used to
      establish the quantitative prediction model based on PLSR. The results showed
      that the best spectral pretreatment of polyphyllin I and II were MSC+OSC+2nd Der
      and that of polyphyllin VII was MSC+SNV+OSC+2nd Der. In the quantitative
      calibration model, the determination coefficients (R2) of polyphyllin I,
      polyphyllin II and polyphyllin VII were 0.930 8, 0.934 8 and 0.912 3,
      respectively while the Root mean square error of estimation(RMSEE) were 1.855 0,
      0.632 3 and 0.001 6 mg*g-1, respectively. In the verification model, the R2 of
      polyphyllin I, polyphyllin II and polyphyllin VII were 0.948 8, 0.703 6 and 0.801
      7, respectively, and the root mean square error of prediction(RMSEP)were 1.704 6,
      1.227 8 and 0.002 0 mg*g-1, respectively. Because of the predictive value of
      quantitative model was closed to the real value, the effect of the model was
      good. The model of polyphyllin I and II were better than that of polyphyllin VII.
      The developed method was non-destructive, fast, and accurate. It was feasible to
      determine the content of polyphyllin in Paris.

PMID- 29192455
TI  - [Molecular mechanism of total flavonoids in Isodon amethystoides on adjuvant
      arthritis in rats].
AB  - Our preliminary study showed that the total flavonoids in Isodon
      amethystoides(TFIA), a local medicinal herb in Suzhou, had a certain therapeutic
      effect on adjuvant arthritis, and this therapeutic effect may be achieved through
      the up-regulation of miR-152 expression. In this paper, the molecular mechanism
      of TFIA on the pathogenesis of adjuvant arthritis(AA) rats was further studied.
      AA rats were prepared with complete Freund's adjuvant, and then treated with TFIA
      by intragastric administration. Real-time qPCR was used to detect the effects of
      TFIA on the negative regulatory loop of miR-152, methylase DNMT1 and methyl-CpG
      binding protein MeCP2 in fibroblast like synoviocytes(FLS) of AA rats, as well as
      the effects of TFIA on the classic Wnt signaling pathway and the expression of
      fibronectin gene in AA rats. Intragastric administration of TFIA significantly
      inhibited the expression of DNMT1 and reversed the negative regulatory loop
      composed of miR-152, DNMT1 and MeCP2 in the pathology of AA rats. After
      transfection of miR-152 inhibitors into the FLS in treatment group, DNMT1
      expression was significantly restored. TFIA significantly up-regulated the
      expression of SFRP4 and inhibited the expression of beta-catenin, C-myc and
      ccnd1, the key genes of canonical Wnt signaling pathway. TFIA also significantly
      inhibited the expression of fibronectin, an AA gene. The effect of TFIA on the
      expression of SFRP4, beta-catenin, C-myc, ccnd1 and fibronectin was reversed
      after transfection with miR-152 inhibitors in the treatment group FLS. TFIA may
      inhibit the DNMT1 expression, up-regulate the SFRP4 expression, inhibit the
      expression of classical Wnt signaling genes beta-catenin, C-myc, and ccnd1 as
      well as the RA gene fibronectin expression through the up-regulation of miR-152
      expression.

PMID- 29192456
TI  - [Pharmacological mechanism analysis of oligopeptide from Pinctada fucata based on
      in silico proteolysis and protein interaction network].
AB  - Pinctada fucata oligopeptide is one of key pharmaceutical effective constituents
      of P. fucata. It is significant to analyze its pharmacological effect and
      mechanism. This study aims to discover the potential oligopeptides from P. fucata
      and analyze the mechanism of P. fucata oligopeptide based on in silico
      technologies and protein interaction network(PIN). First, main protein sequences
      of P. fucata were collected, and oligopeptides were obtained using in silico
      gastrointestinal tract proteolysis. Then, key potential targets of P. fucata
      oligopeptides were obtained through pharmacophore screening. The protein-protein
      interaction(PPI) of targets was achieved and implemented to construct PIN and
      analyze the mechanism of P. fucata oligopeptides. P. fucata oligopeptide database
      was constructed based on in silico technologies, including 458 oligopeptides.
      Twelve modules were identified from PIN by a graph theoretic clustering algorithm
      Molecular Complex Detection(MCODE) and analyzed by Gene ontology(GO) enrichment.
      The results indicated that P. fucata oligopeptides have an effect in treating
      neurological diseases, such as Alzheimer's disease. In silico proteolysis could
      be used to analyze the protein sequences of traditional Chinese medicine(TCM).
      According to the combination of in silico proteolysis and PIN, the biological
      activity of oligopeptides could be interpreted rapidly based on the known TCM
      protein sequence. The study provides the methodology basis for rapidly and
      efficiently implementing the mechanism analysis of TCM oligopeptides.

PMID- 29192457
TI  - [Pharmacological mechanism analysis of oligopeptide from Pinctada fucata based on
      in silico proteolysis and protein interaction network].
AB  - Thoracic obstruction is mainly attributed to the scope of coronary heart disease
      in modern medicine, and traditional Chinese medicine(TCM) shows a significant
      effect in the treatment of thoracic obstruction. In this research, a network
      pharmacology method was carried out to systemically study the underlying
      mechanism of the core herbal compatibility in TCM on the thoracic obstruction.
      First, we collected the literature about TCM prescriptions for treating thoracic
      obstruction from CNKI. Then, a prescription database was establish by TCM
      inheritance support platform system(V2.5) to determine the medication rules and
      core herbal compatibility in TCM. Finally, to obtain the potential signaling
      pathways, KEGG pathway analysis was performed by BATMAN-TCM online analysis tool.
      Results showed that the potential signal pathway of core herbal compatibility in
      TCM for the clinical treatment of thoracic obstruction was calcium ion and cGMP
      PKG signaling pathway. This study provided a new research strategy for the study
      of the medication rules and mechanism of traditional Chinese medicine in the
      treatment of thoracic obstruction.

PMID- 29192458
TI  - [Exploring the clinical characters of Shugan Jieyu capsule through text mining].
AB  - The study was main to explore the clinical characters of Shugan Jieyu capsule
      through text mining. The data sets of Shugan Jieyu capsule were downloaded from
      CMCC database by the method of literature retrieved from May 2009 to Jan 2016.
      Rules of Chinese medical patterns, diseases, symptoms and combination treatment
      were mined out by data slicing algorithm, and they were demonstrated in frequency
      tables and two dimension based network. Then totally 190 literature were
      recruited. The outcomess suggested that SC was most frequently correlated with
      liver Qi stagnation. Primary depression, depression due to brain disease,
      concomitant depression followed by physical diseases, concomitant depression
      followed by schizophrenia and functional dyspepsia were main diseases treated by
      Shugan Jieyu capsule. Symptoms like low mood, psychic anxiety, somatic anxiety
      and dysfunction of automatic nerve were mainy relieved bv Shugan Jieyu
      capsule.For combination treatment. Shugan Jieyu capsule was most commonly used
      with paroxetine, sertraline and fluoxetine. The research suggested that syndrome
      types and mining results of Shugan Jieyu capsule were almost the same as its
      instructions. Syndrome of malnutrition of heart spirit was the potential Chinese
      medical pattern of Shugan Jieyu capsule. Primary comorbid anxiety and depression,
      concomitant comorbid anxiety and depression followed by physical diseases, and
      postpartum depression were potential diseases treated by Shugan Jieyu capsule.For
      combination treatment, Shugan Jieyu capsule was most commonly used with
      paroxetine, sertraline and fluoxetine.

PMID- 29192459
TI  - Meeting of the Strategic Advisory Group of Experts on immunization, October 2017 
      conclusions and recommendations.

PMID- 29192460
TI  - [Sexual health and intellectual disability: a narrative literature review and its
      implications for nursing practice.]
AB  - Issues associated with affectivity and sexuality in the context of intellectual
      disability have recently been the subject of various interdisciplinary
      discussions in academia. In nursing, interventions in sexual health are supported
      with hesitation and those issues constitute a marginal field of nursing research.
      A narrative literature review was realized in order to establish a portrait of
      the knowledge produced on this topic in the last decade. This paper illustrates
      three specific research areas recently developed, namely issues related to sexual
      autonomy, contextual factors positively or negatively contributing to emotional
      and sexual life, and the experiences of people identified as having an
      intellectual disability in this regard. On the basis of these results, different
      issues related to sexuality and intellectual disability are discussed, including
      those associated with the negotiation process of affective and sexual life,
      parenthood as a mediator of emotional and sexual expression, and the
      inclusiveness issues of sexual diversity in health interventions. Implications
      for nursing are finally discussed in light of the recent development of its role
      in sexual health.

PMID- 29192461
TI  - [The organizational projects management led by head nurses: qualitative study
      from an educational device.]
AB  - The work of operational coordination led by head nurses (HN) is more known than
      their abilities to change work organization, as well as, care practices. In this
      article, we explore organizational projects led by HN. Depending on the
      situations, they may concern their health care team or involve institutional
      hierarchy or other teams. We rely on an intervention study, which enabled us to
      follow 17 organizational projects led by HN for one year. The results of this
      study highlight as the main condition for success, the HN' efforts to enable
      mutual understanding with other interested actors. Managers, who engage their
      health care team in the development of solutions, bring sustainable results. When
      problems involve the hierarchy, the managers focus on the development of personal
      relationships. When problems involve other departments, which they depend on,
      then they engage themselves into integrative negotiations. These results invite
      to open discussion about work organization and to formalize organizational
      projects. This intervention study also points out that work - training at
      operational audit is relevant for HN. Active par Editorial Manager(r) et
      ProduXion.

PMID- 29192462
TI  - ?

PMID- 29192463
TI  - [Healthcare Provider Professional Secrecy: an Issue for Public Health Democracy
      somewhere between Immanence and Alienation.]
AB  - For a long time considered as total and absolute, healthcare professional secrecy
      is today difficult to reconcile with care practices. Lots of paradoxes question
      its preservation in favour of general interest and public order against the
      protection of private interest within an individualistic normative society.
      Exploring this interrogation, the article's objective is to initiate an ethical
      discussion from a professional caregiver secrecy's historical and sociological
      evolution perspective. Thus, with the help of theoretical understandings,
      especially those by Michel Foucault, medical secrecy is considered a defense of
      rationality specific to populations' government. This conceptualization finds
      arguments through social collective norms attached to an alienating biopower at
      the expense of secrecy integrated as an individualistic and immanent social norm.
      However, beyond the well-known debate on the absolute necessity for change,
      evolution... the distance from the Socratic and Hippocratic principles engage
      people and society in real democratic decisions about Health. Also, health
      professionals, patients, usgers and society must consider the limits that would
      lead to medical confidentiality.

PMID- 29192464
TI  - [The person and the ethics of care.]
AB  - In our western world, it has long been thought that humans are exceptions within
      nature. They have defined themselves as human beings as opposed to animals and
      things, on account of characteristics that they regarded as essential. However it
      now seems necessary to question this perception of humanity and the human
      condition.Indeed, longer life expectancy together with its related pathologies
      and medical progress lead us to think differently. Today we realise that those
      qualities which were thought to belong specifically to human beings, such as
      awareness, reason, memory and free will, can disappear. Should we conclude then
      that those whose capacities have decreased or disappeared have become less human
      or have even lost all human qualities?Such questioning leads to new ways of
      describing humans whereby they would be defined not in substantial but rather in
      interpersonal terms.Surely being a person means first and foremost that we live
      through and for others. And the ethics of care that define men as vulnerable
      beings, that is to say dependent and needing their fellow human beings'
      solicitude, would surely offer the possibility of creating a new ?revisited'
      concept of the person?

PMID- 29192465
TI  - [When nursing teacher's authority and education relationship have to deal with
      cell-phones in class.]
AB  - : In nursing institut teachers accompany students with whom they establish a
      pedagogical relationship, while guaranteeing compliance with internal rules,
      particularly concerning the banning of mobile phones during teaching. This
      complex double mission includes, among others, the forbidding of cell phones in
      classroom. OBJECTIVE: this study aims at understanding the involved relational
      mechanism through the following question: how teachers articulate pedagogical
      relationship with their required authority at the same time? METHODOLOGY:
      qualitative study performed between 2015 and 2016 using semi structured
      interviews interviews of teachers and students of the nursing school. RESULTS:
      teachers give importance to the quality of relationship, but arrange differently
      to link authority and training missions. Students accept and recognize this
      authority as it is part of the internal rules. This legitimacy allows setting up
      a cooperative pedagogical relation. The internal rules contribute to build up the
      authority of teachers' team. CONCLUSION: This study opens perspectives for
      reflection on the notions of relationship, rules, legitimacy and collaboration.
      Authority is a complex phenomenon which fits, just like pedagogical relation, in
      a frame providing stability and legitimacy. The internal rules would not
      standardize the behaviors, but would allow expressing individual liberty.

PMID- 29192466
TI  - [The characteristics of the resilience tutors for weakened nursing students.]
AB  - Nursing training seems to make students vulnerable to stress or burnout.
      Nevertheless, the majority succeeded in this training. This positive recovery
      despite a deleterious context of study questions about this schooling, and on
      possible resilient mechanisms and tutors of resilience. This research paper in
      educational sciences will begin with a synthesis of the results of publications
      about stressors and risk's factors of burnout of these students. We will see how
      this schooling can be linked to the concept of vulnerability and resilience.
      Then, we will present the results and the thematic analysis of 30 semi-directive
      interviews. The objectives of those ones were: to check factors vulnerability of
      this training, to determine if resilient processes can be observed, and to
      identify the characteristics of the resilience tutors of these weakened students.
      After the presentation of the results and of the analysis, we will discuss the
      links between vulnerability, post-traumatic stress disorder and burnout. We will
      explain the concept of compassion as one of the predominant characteristics of
      tutors. Finally, concerning the relational posture of education's professionals,
      we will show how they could professionally support students' resilience.

PMID- 29192467
TI  - It's back-to-school time.

PMID- 29192468
TI  - Can a single drug administration elicit two different immunological pathways at
      the same time? A case report of Fixed Drug Eruption after anaphylaxis.

PMID- 29192469
TI  - Milk thistle and olive extract: old substances with a new mission against sun
      induced skin damage.
AB  - BACKGROUND: Natural antioxidants represent an effective option in the prevention
      and/or improvement of ultraviolet radiations (UVR)-induced/aggravated skin
      conditions. UVR cause DNA damage in keratinocytes, directly, in the form of
      cyclobutane pyrimidine dimers (CPDs), or indirectly, through oxidative stress
      production. Failure of the repair system can result in genetic mutations
      primarily responsible for the initiation of NMSCs. The aim of our study was to
      evaluate the in vitro protective effect of milk thistle and olive purified
      extracts on cultured keratinocytes after solar simulator irradiations (SSR).
      METHODS: Immortalized keratinocytes were pre-incubated with different
      concentrations of milk thistle and olive purified extracts, and irradiated with
      increasing doses of SSR. Thereafter, CPDs and p53 expression were evaluated to
      assess DNA damage, whereas cellular antioxidants consumption and lipid membranes
      peroxidation were measured to analyse oxidative stress. RESULTS: The study
      substances were well tolerated by cells and displayed good cytoprotective and
      anti-oxidant activities, being milk thistle dry extract more effective in
      limiting the direct DNA damage, and olive extract particularly able to reduce
      lipid membrane peroxidation and to increase cellular antioxidants. CONCLUSIONS:
      Both study substances can be defined as safe compounds, showing differential
      cytoprotective and anti-oxidant activities and might represent interesting
      options for NMSCs chemoprevention.

PMID- 29192470
TI  - The STRIPP questionnaire (Screening Tool for Rheumatologic Investigation in
      Psoriatic Patients) as a new tool for the diagnosis of early psoriatic arthritis.
AB  - BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthritis associated
      with psoriasis in up to one third of psoriatic patients. Clinically it's
      characterized from an insidious onset. To help clinicians screen for PsA, several
      screening tools have been developed. The psoriatic arthritis screening and
      evaluation questionnaire (PASE) is one of the most used in the Psocare units. The
      sensibility of PASE is of 83% with a cut off of 47 or greater. The aim of our
      study is to create an Italian self-administered questionnaire, lighter than the
      PASE, able to identify patients who need a rheumatologic consultation. METHODS:
      Between April and June 2016 an Italian group of dermatologists and
      rheumatologists from north Italy developed a new questionnaire called Screening
      Tool for Rheumatologic Investigation in Psoriatic Patient (STRIPP). Two hundred
      and twelve patients with the diagnosis of psoriasis, were screened with STRIPP by
      dermatologists and all of them sent to the rheumatologist. RESULTS: Forty seven
      out of 212 patients received the diagnosis of early psoriatic arthritis.
      Statistical analysis (Spearman Rank correlation test, Mann Whitney test) showed a
      specificity of 93.3% and a sensibility of 91.5% taking a point of 3.5 as a cut
      off. CONCLUSIONS: The STRIPP is a very easy questionnaire, quick to out and has a
      very high sensitivity and specificity, higher than the PASE. Our future goal will
      be to screen more patients for validating the STRIPP questionnaire.

PMID- 29192471
TI  - Biologic agents perception in patients attending for the first-time to psoriasis
      centers: a multicenter Italian survey.
AB  - BACKGROUND: Inadequate treatment and delayed access to care represent critical
      issues regarding psoriasis. In Italy, patients treated with biologics are scanty
      and patients' misinformation could interfere with both biologics prescription and
      access to care. Literature provide data on disease awareness and perception about
      biologics in already-treated patients, but there is a lack of information
      concerning patients never treated with such drugs. METHODS: We conducted a
      national survey including three academic-based psoriasis care centers at Bologna,
      Rome and Catania. A questionnaire named Psoriatic Patients's Awareness on
      Biologics (PPAB) was administered to patients naive for biologics and accessing
      for the fist-time to a psoriasis care center. RESULTS: Patients from Northern
      Italy referred to more reliable sources of information and awareness on biologics
      decreased from North to South. The increase of the Psoriasis Area Severity Index
      was associated to unawareness about biologics and impaired self-evaluation on the
      eligibility to treatment. Patients under systemic conventional/multiple therapy
      were more likely to be unaware about biologics. CONCLUSIONS: Our survey
      demonstrates that psoriatic patients' awareness is still an unmet need. For more,
      patients potentially eligible for biologics (severe or treated with systemic
      conventional/multiple therapy) were less informed. We believe that patients'
      misinformation could have delayed the access to a psoriasis care center, so that
      when patients sought help their condition was more severe and required systemic
      conventional/multiple therapy. Our results reiterate the importance of physicians
      in the information process and urge the need of a common network among office
      dermatologists, general practitioners and psoriasis care centers.

PMID- 29192472
TI  - Photosensitivity in drug induced pellagra.

PMID- 29192473
TI  - Severe adverse drug reaction due to Cypress sublingual immunotherapy.

PMID- 29192474
TI  - Classical Kaposi's Sarcoma (KS) concurrent with Ledipasvir-Sofosbuvir therapy for
      Hepatitis C infection (HCV).

PMID- 29192475
TI  - Yellow skin discoloration in a 4 years-old girl with type 1 diabetes mellitus.

PMID- 29192476
TI  - Melanonychia induced by venlafaxine hydrochloride.

PMID- 29192477
TI  - Mast cells and cancer: a review of literature.
AB  - Mast cells (MCs) are a potent proangiogenic factor in tumors, they product
      several pro- angiogenic factors such as fibroblast growth factor 2 (FGF-2),
      vascular epithelial growth factor (VEGF), tryptase and chymase. Tryptase is a
      serine protease classified as alpha-tryptase and beta-tryptase, both produced by
      MCs. Tryptase degrades the tissues, playing an important role in angiogenesis and
      in the development of metastases. Serum tryptase increases with age, with
      increased damage to cells and risk of developing a malignancy and it could be
      considered the expression of a fundamental role of MCs in tumor growth or, on the
      contrary, in the antitumor response. Many biomarkers have been developed in
      clinical practice for improving diagnosis and prognosis of some neoplasms.
      Elevated tryptase levels are found in subgroups of patients with haematologic and
      solid cancers. In the current review, we want to update the perspectives of
      tryptase as a potential biomarker in daily practice in different neoplasms.

PMID- 29192478
TI  - 2015 snapshot of regulated nurses.

PMID- 29192479
TI  - New health policies approved at two federal conventions.

PMID- 29192480
TI  - Her watchwords: Resonance, reverberation and relevance.

PMID- 29192481
TI  - Meet the millennials: A new generation of nursing leaders.

PMID- 29192482
TI  - B12 supplementation: Making the switch.

PMID- 29192483
TI  - It's about living.

PMID- 29192484
TI  - With high hopes.

PMID- 29192485
TI  - National health issues raised in Whitehorse.

PMID- 29192486
TI  - Insightful debates at annual meeting.

PMID- 29192487
TI  - Cation Diffusion and Segregation at the Interface between Samarium-Doped Ceria
      and LSCF or LSFCu Cathodes Investigated with X-ray Microspectroscopy.
AB  - The chemical compatibility between electrolytes and electrodes is an extremely
      important aspect governing the overall impedance of solid-oxide cells. Because
      these devices work at elevated temperatures, they are especially prone to cation
      interdiffusion between the cell components, possibly resulting in secondary
      insulating phases. In this work, we applied X-ray microspectroscopy to study the
      interface between a samarium-doped ceria (SDC) electrolyte and lanthanum ferrite
      cathodes (La0.4Sr0.6Fe0.8Cu0.2O3 (LSFCu); La0.9Sr0.1Fe0.85Co0.15O3 (LSCF)), at a
      submicrometric level. This technique allows to combine the information about the
      diffusion profiles of cations on the scale of several micrometers, together with
      the chemical information coming from space-resolved X-ray absorption
      spectroscopy. In SDC-LSCF bilayers, we find that the prolonged thermal treatments
      at 1150  degrees C bring about the segregation of samarium and iron in micrometer
      sized perovskite domains. In both SDC-LSCF and SDC-LSFCu bilayers, cerium
      diffuses into the cathode perovskite lattice A-site as a reduced Ce3+ cation,
      whereas La3+ is easily incorporated in the ceria lattice, reaching 30 atom % in
      the ceria layer in contact with LSFCu.

PMID- 29192488
TI  - Self-Assembly High-Performance UV-vis-NIR Broadband beta-In2Se3/Si Photodetector
      Array for Weak Signal Detection.
AB  - The emergence of a rich variety of layered materials has attracted considerable
      attention in recent years because of their exciting properties. However, the
      applications of layered materials in optoelectronic devices are hampered by the
      low light absorption of monolayers/few layers, the lack of p-n junction, and the
      challenges for large-scale production. Here, we report a scalable production of
      beta-In2Se3/Si heterojunction arrays using pulsed-laser deposition.
      Photodetectors based on the as-produced heterojunction array are sensitive to a
      broadband wavelength from ultraviolet (370 nm) to near-infrared (808 nm), showing
      a high responsivity (5.9 A/W), a decent current on/off ratio (~600), and a
      superior detectivity (4.9 * 1012 jones), simultaneously. These figures-of-merits
      are among the best values of the reported heterojunction-based photodetectors. In
      addition, these devices can further enable the detection of weak signals, as
      successfully demonstrated with weak light sources including a flashlight,
      lighter, and fluorescent light. Device physics modeling shows that their high
      performance is attributed to the strong light absorption of the relatively thick
      beta-In2Se3 film (20.3 nm) and the rational energy band structures of beta-In2Se3
      and Si, which allows efficient separation of photoexcited electron-hole pairs.
      These results offer a new insight into the rational design of optoelectronic
      devices from the synergetic effect of layered materials as well as mature
      semiconductor technology.

PMID- 29192489
TI  - Growth of 2D Mesoporous Polyaniline with Controlled Pore Structures on Ultrathin
      MoS2 Nanosheets by Block Copolymer Self-Assembly in Solution.
AB  - The development of versatile strategies toward two-dimensional (2D) porous
      nanocomposites with tunable pore structures draws immense scientific attention in
      view of their attractive physiochemical properties and a wide range of promising
      applications. This paper describes a self-assembly approach for the directed
      growth of mesoporous polyaniline (PANi) with tunable pore structures and sizes on
      ultrathin freestanding MoS2 nanosheets in solution, which produces 2D mesoporous
      PANi/MoS2 nanocomposites. The strategy employs spherical and cylindrical
      micelles, which are formed by the controlled solution self-assembly of block
      copolymers, as the soft templates for the construction of well-defined spherical
      and cylindrical mesopores in the 2D PANi/MoS2 nanocomposites, respectively. With
      potential applications as supercapacitor electrode materials, the resultant 2D
      composites show excellent capacitive performance with a maximum capacitance of
      500 F g-1 at a current density of 0.5 A g-1, good rate performance, as well as
      outstanding stability for charge-discharge cycling. Moreover, the 2D mesoporous
      nanocomposites offer an opportunity for the study on the influence of different
      pore structures on their capacitive performance, which helps to understand the
      pore structure-property relationship of 2D porous electrode materials and to
      achieve their electrochemical performance control.

PMID- 29192490
TI  - Nanostructured Gold Microelectrode Array for Ultrasensitive Detection of Heavy
      Metal Contamination.
AB  - Availability of potable water is a problem especially in developing countries as
      their water sources are often contaminated biologically as well as by heavy
      metals. Electrochemical methods are suitable for field application to monitor
      heavy metal contents. Noble metal electrodes with large surface areas are the
      subject of intensive development as they can yield an improved signal-to-noise
      ratio, enhanced sensitivity, and lower limits of detection (LOD). Here, we
      present a nanostructured Au microelectrode array subsequently modified by
      selective electrodeposition in lithographically defined circles within a
      partially cross-linked gelatin layer. This method increased its surface area by a
      factor of ~1440 in comparison with an original lithography-based prepared array.
      The Au surface properties can be tailored by a degree of gelatin layer cross
      linking. We used this array for an ultrasensitive detection of the As3+ ions
      content by stripping voltammetry achieving LOD of ~0.0212 parts per billion
      (signal-to-noise ratio = 3.3), 470* below the content limit recommended by the
      World Health Organization for potable water. These nanostructured arrays were
      used to detect ions of other metals such as Cr, Cd, Hg, Cu, and Sb. In
      combination with a portable electrochemical device, we can envision an
      ultrasensitive heavy metal detection system for field application to monitor
      heavy metal contamination.

PMID- 29192491
TI  - Bright Tail States in Blue-Emitting Ultrasmall Perovskite Quantum Dots.
AB  - All-inorganic lead halide perovskite quantum dots (CsPbBr3 QDs) are attracting
      significant research interests because of their highly efficient light-emitting
      performance combined with tunable emission wavelength facilely realized by ion
      exchange. However, blue emission from perovskite QDs with strong quantum
      confinement is rarely reported and suffers from lower luminescence efficiency.
      Here we report blue-emitting ultrasmall (~3 nm) CsPbBr3 QDs with
      photoluminescence (PL) quantum yield as high as 68%. Using time-resolved and
      steady-state PL spectroscopy, we elucidate the mechanism of the highly efficient
      PL as recombination of excitons localized in radiative band tail states. Through
      analyzing the spectral-dependent PL lifetime and the PL line shape, we obtain a
      large band tail width of ~80 meV and a high density of state of ~1020 cm-3. The
      relaxation of photocarriers into the radiative tail states suppresses the capture
      by nonradiative centers. Our results provide solid evidence for the positive role
      of band tail states in the optical properties of lead halide perovskites, which
      can be further tailored for high-performance optoelectronic devices.

PMID- 29192492
TI  - MoSe2 Nanosheet Array with Layered MoS2 Heterostructures for Superior Hydrogen
      Evolution and Lithium Storage Performance.
AB  - Engineering heterostructures of transition metal disulfides through low-cost and
      high-yield methods instead of using conventional deposition techniques still have
      great challenges. Herein, we present a conveniently operated and low-energy
      consumption solution-processed strategy for the preparation of heterostructures
      of MoSe2 nanosheet array on layered MoS2, among which the two-dimensional MoS2
      surface is uniformly covered with high-density arrays of vertically aligned
      MoSe2. The unique compositional and structural features of the MoS2-MoSe2
      heterostructures not only provide more exposed active sites for sequent
      electrochemical process, but also facilitate the ion transfer due to the open
      porous space within the nanosheet array serving as well-defined ionic reservoirs.
      As a proof of concept, the MoS2-MoSe2 heterostructures serve as promising
      bifunctional electrodes for both energy conversions and storages, which exhibit
      an active and acid-stable activity for catalyzing the hydrogen evolution
      reaction, high specific capacity of 728 F g-1 at 0.1 A g-1, and excellent
      durability with a remained capacity as high as 676 mA h g-1 after 200 cycles.

PMID- 29192493
TI  - Biodegradable Metal Ion-Doped Mesoporous Silica Nanospheres Stimulate Anticancer
      Th1 Immune Response in Vivo.
AB  - Modern vaccines usually require accompanying adjuvants to increase the immune
      response to antigens. Aluminum (alum) compounds are the most commonly used
      adjuvants in human vaccinations for infection diseases. However, alum adjuvants
      are nondegradable, cause side effects due to the persistence of alum at injection
      sites, and are rather ineffective for cancer immunotherapy, which requires the
      Th1 immune response. Recently, we have shown that a plain mesoporous silica (MS)
      adjuvant can stimulate Th1 anticancer immunity for cancer vaccines. Herein, MS
      nanospheres doped with Ca, Mg, and Zn (MS-Ca, MS-Mg, and MS-Zn) showed
      significantly higher degradation rates than pure MS. Moreover, MS-Ca, MS-Mg, and
      MS-Zn nanospheres  stimulated anticancer immune response and increased the CD4+
      and CD8+ T cell populations in spleen. The MS-Ca, MS-Mg, and MS-Zn nanospheres
      with improved biodegradability and excellent ability to induce Th1 anticancer
      immunity show potential for clinical applications as cancer immunoadjuvants.

PMID- 29192494
TI  - Regulated and Unregulated Halogenated Flame Retardants in Peregrine Falcon Eggs
      from Greenland.
AB  - Median levels of regulated flame retardants, i.e., polybrominated diphenyl ethers
      (PBDEs), brominated biphenyl (BB)-153, and hexabromocyclododecane (HBCD), in 33
      48 eggs of peregrine falcons (Falco peregrinus) from Greenland were 1909, 359,
      and 5.98 ng/g lipid weight (lw), respectively, and generally intermediate to
      levels in North America and Europe. Unregulated flame retardants had lower median
      concentrations of 1.06 (2-ethylhexyl-2,3,4,5-tetrabromobenzoate, EH-TBB), 2.42
      (1,2-bis(2,4,6-tribromophenoxy)-ethane, BTBPE), 0.52 (2,4,6-tribromophenyl 2,3
      dibromopropyl ether, DPTE), and 4.78 (dechlorane plus) ng/g lw. Although these
      compounds are often described as recent replacements for PBDEs, they were also
      present in eggs from the 1980s. BDE-209 was the only compound with a significant
      increase (+7.2% annual change) between 1986 and 2014, while BB-153 and DPTE
      decreased significantly (-8.0% and -2.8% annual change, respectively). Dechlorane
      plus showed a nonsignificant increase. Individual birds, equipped with light
      logging geolocators, confirmed the contaminant exposure over a large geographical
      area as the birds spent nearly equal time periods in their breeding and wintering
      grounds in Greenland and Central/South America, respectively, interrupted by 5-6
      weeks of migration through North America.

PMID- 29192495
TI  - Novel Surface Molecular Functionalization Route To Enhance Environmental
      Stability of Tellurium-Containing 2D Layers.
AB  - Recent studies have shown that tellurium-based two-dimensional (2D) crystals
      undergo dramatic structural, physical, and chemical changes under ambient
      conditions, which adversely impact their much desired properties. Here, we
      introduce a diazonium molecule functionalization-based surface engineering route
      that greatly enhances their environmental stability without sacrificing their
      much desired properties. Spectroscopy and microscopy results show that diazonium
      groups significantly slow down the surface reactions, and consequently, gallium
      telluride (GaTe), zirconium telluride (ZrTe3), and molybdenum ditelluride (MoTe2)
      gain strong resistance to surface transformation in air or when immersed under
      water. Density functional theory calculations show that functionalizing molecules
      reduce surface reactivity of Te-containing 2D surfaces by chemical binding
      followed by an electron withdrawal process. While pristine surfaces structurally
      decompose because of strong reactivity of Te surface atoms, passivated
      functionalized surfaces retain their structural anisotropy, optical band gap, and
      emission characteristics as evidenced by our conductive atomic force microscopy,
      photoluminescence, and absorption spectroscopy measurements. Overall, our
      findings offer an effective method to increase the stability of these
      environmentally sensitive materials without impacting much of their physical
      properties.

PMID- 29192496
TI  - Solution Processed CH3NH3PbI3-xClx Perovskite Based Self-Powered Ozone Sensing
      Element Operated at Room Temperature.
AB  - Hybrid lead halide spin coated perovskite films have been successfully tested as
      portable, flexible, operated at room temperature, self-powered, and
      ultrasensitive ozone sensing elements. The electrical resistance of the hybrid
      lead mixed halide perovskite (CH3NH3PbI3-xClx) sensing element, was immediately
      decreased when exposed to an ozone (O3) environment and manage to recover its
      pristine electrical conductivity values within few seconds after the complete
      removal of ozone gas. The sensing measurements showed different response times at
      different gas concentrations, good repeatability, ultrahigh sensitivity and fast
      recovery time. To the best of our knowledge, this is the first time that a lead
      halide perovskite semiconductor material is demonstrating its sensing properties
      in an ozone environment. This work shows the potential of hybrid lead halide
      based perovskites as reliable sensing elements, serving the objectives of
      environmental control, with important socioeconomic impact.

PMID- 29192497
TI  - Identification of New Anti-inflammatory Peptides from Zein Hydrolysate after
      Simulated Gastrointestinal Digestion and Transport in Caco-2 Cells.
AB  - Chronic inflammation is an underlying contributor to various chronic diseases.
      The objectives of this study were to investigate the anti-inflammatory activity
      of zein hydrolysate after simulated gastrointestinal digestion and Caco-2 cell
      absorption and to identify novel anti-inflammatory peptides after transport
      across Caco-2 cells. Three zein hydrolysates were prepared and further digested
      using gastrointestinal proteases; their transports were studied in Caco-2 cells.
      Anti-inflammatory activity was studied in endothelial EA.hy926 cells. Three zein
      hydrolysates and their digests significantly decreased the expression of tumor
      necrosis factor-alpha (TNF-alpha) induced pro-inflammatory vascular cell adhesion
      molecule-1 (VCAM-1) by 37.3-66.0%. Eleven novel peptides with 5-9 amino acid
      residues were sequenced; three peptides showed strong anti-inflammatory activity
      by inhibiting the VCAM-1 by 54-38.9% and intercellular cell adhesion molecule-1
      (ICAM-1) by 36.5-28.6% at 0.2 mM. A new approach to identify novel anti
      inflammatory peptides that could survive gastrointestinal digestion and
      absorption was developed.

PMID- 29192499
TI  - Copper-Catalyzed Oxidative Perfluoroalkylation of Aryl Boronic Acids Using
      Perfluoroalkylzinc Reagents.
AB  - An efficient and synthetically convenient method for copper-catalyzed cross
      coupling of aryl boronic acids with perfluoroalkyl zinc reagents has been
      described. The reaction proceeds under mild reaction conditions with a high
      efficiency and broad substrate scope and provides a general access to
      perfluoroalkylated arenes, which are of interest in life and materials science.

PMID- 29192498
TI  - Membrane Protein Structure in Live Cells: Methodology for Studying Drug
      Interaction by Mass Spectrometry-Based Footprinting.
AB  - Mass spectrometry-based footprinting is an emerging approach for studying protein
      structure. Because integral membrane proteins are difficult targets for
      conventional structural biology, we recently developed a mass spectrometry (MS)
      footprinting method to probe membrane protein-drug interactions in live cells.
      This method can detect structural differences between apo and drug-bound states
      of membrane proteins, with the changes inferred from MS quantification of the
      cysteine modification pattern, generated by residue-specific chemical labeling.
      Here, we describe the experimental design, interpretation, advantages, and
      limitations of using cysteine footprinting by taking as an example the
      interaction of warfarin with vitamin K epoxide reductase, a human membrane
      protein. Compared with other structural methods, footprinting of proteins in live
      cells produces structural information for the near native state. Knowledge of
      cellular conformational states is a necessary complement to the high-resolution
      structures obtained from purified proteins in vitro. Thus, the MS footprinting
      method is broadly applicable in membrane protein biology. Future directions
      include probing flexible motions of membrane proteins and their interaction
      interface in live cells, which are often beyond the reach of conventional
      structural methods.

PMID- 29192500
TI  - Comparative Proteomics of Contrasting Maize Genotypes Provides Insights into Salt
      Stress Tolerance Mechanisms.
AB  - Salt stress is a major abiotic factor limiting maize yield. To characterize the
      mechanism underlying maize salt tolerance, we compared the seedling root
      proteomes of salt-tolerant Jing724 and salt-sensitive D9H. The germination rate
      and growth parameter values (weight and length) were higher for Jing724 than for
      D9H under saline conditions. Using an iTRAQ-based method, we identified 513
      differentially regulated proteins (DRPs), with 83 and 386 DRPs specific to
      Jing724 and D9H, respectively. In salt-stressed Jing724, the DRPs were primarily
      associated with the pentose phosphate pathway, glutathione metabolism, and
      nitrogen metabolism. Key DRPs, such as glucose-6-phosphate 1-dehydrogenase, NADPH
      producing dehydrogenase, glutamate synthase, and glutamine synthetase, were
      identified based on pathway enrichment and protein-protein interaction analyses.
      Moreover, salt-responsive proteins in Jing724 seedlings were implicated in energy
      management, maintenance of redox homeostasis, detoxification of ammonia,
      regulation of osmotic homeostasis, stress defense and adaptation, biotic cross
      tolerance, and regulation of gene expression. Quantitative analyses of superoxide
      dismutase activity, malondialdehyde content, relative electrolyte leakage, and
      proline content were consistent with the predicted changes based on DRP
      functions. Furthermore, changes in the abundance of eight representative DRPs
      were correlated with the corresponding mRNA levels. Our results may be useful for
      elucidating the molecular networks mediating salt tolerance.

PMID- 29192501
TI  - All Organic Label-like Copper(II) Ions Fluorescent Film Sensors with High
      Sensitivity and Stretchability.
AB  - Deep learning and analysis of heavy metal concentration are very crucial to our
      life, for it plays an essential role in both environmental and human health. In
      this paper, we developed a new Cu (II) ions sensor made by all organic material
      with bending and stretching properties. The new sensor consists of chlorophyll-a
      extracted from fresh leaves of Common Garcinia, plant fiber and with the use of
      PDMS as a substrate. Fluorescence spectra study shows that chlorophyll-a is
      significantly much more sensitive to Cu (II) ions than any other heavy metal ions
      and the device sensitivity outperforms all the Cu (II) ions sensors ever
      reported. The result fully shows the selectivity of chlorophyll-a toward Cu (II)
      ions. Bending and stretching tests show that the sensor has an outstanding
      durability, which can be used to develop accompanying applications, such as real
      time sampling and the analysis of Cu (II) concentration specified in athlete's
      sweat or patients with brain death and Parkinson's disease.

PMID- 29192502
TI  - Ferrous Iron Oxidation under Varying pO2 Levels: The Effect of Fe(III)/Al(III)
      Oxide Minerals and Organic Matter.
AB  - Abiotic Fe(II) oxidation by O2 commonly occurs in the presence of mineral
      sorbents and organic matter (OM) in soils and sediments; however, this tertiary
      system has rarely been studied. Therefore, we examined the impacts of mineral
      surfaces (goethite and gamma-Al2O3) and organic matter [Suwannee River fulvic
      acid (SRFA)] on Fe(II) oxidation rates and the resulting Fe(III) (oxyhydr)oxides
      under 21 and 1% pO2 at pH 6. We tracked Fe dynamics by adding 57Fe(II) to 56Fe
      labeled goethite and gamma-Al2O3 and characterized the resulting solids using
      57Fe Mossbauer spectroscopy. We found Fe(II) oxidation was slower at low pO2 and
      resulted in higher-crystallinity Fe(III) phases. Relative to oxidation of
      Fe(II)(aq) alone, both goethite and gamma-Al2O3 surfaces increased Fe(II)
      oxidation rates regardless of pO2 levels, with goethite being the stronger
      catalyst. Goethite surfaces promoted the formation of crystalline goethite, while
      gamma-Al2O3 favored nano/small particle or disordered goethite and some
      lepidocrocite; oxidation of Fe(II)aq alone favored lepidocrocite. SRFA reduced
      oxidation rates in all treatments except the mineral-free systems at 21% pO2, and
      SRFA decreased Fe(III) phase crystallinity, facilitating low-crystalline
      ferrihydrite in the absence of mineral sorbents, low-crystalline lepidocrocite in
      the presence of gamma-Al2O3, but either crystalline goethite or ferrihydrite when
      goethite was present. This work highlights that the oxidation rate, the types of
      mineral surfaces, and OM control Fe(III) precipitate composition.

PMID- 29192503
TI  - Dynamics of Nanoparticles in Entangled Polymer Solutions.
AB  - The mean square displacement ?r2? of nanoparticle probes dispersed in simple
      isotropic liquids and in polymer solutions is interrogated using fluorescence
      correlation spectroscopy and single-particle tracking (SPT) experiments. Probe
      dynamics in different regimes of particle diameter (d), relative to
      characteristic polymer length scales, including the correlation length (xi), the
      entanglement mesh size (a), and the radius of gyration (Rg), are investigated. In
      simple fluids and for polymer solutions in which d ? Rg, long-time particle
      dynamics obey random-walk statistics ?r2?:t, with the bulk zero-shear viscosity
      of the polymer solution determining the frictional resistance to particle motion.
      In contrast, in polymer solutions with d < Rg, polymer molecules in solution
      exert noncontinuum resistances to particle motion and nanoparticle probes appear
      to interact hydrodynamically only with a local fluid medium with effective drag
      comparable to that of a solution of polymer chain segments with sizes similar to
      those of the nanoparticle probes. Under these conditions, the nanoparticles
      exhibit orders of magnitude faster dynamics than those expected from continuum
      predictions based on the Stokes-Einstein relation. SPT measurements further show
      that when d > a, nanoparticle dynamics transition from diffusive to subdiffusive
      on long timescales, reminiscent of particle transport in a field with
      obstructions. This last finding is in stark contrast to the nanoparticle dynamics
      observed in entangled polymer melts, where X-ray photon correlation spectroscopy
      measurements reveal faster but hyperdiffusive dynamics. We analyze these results
      with the help of the hopping model for particle dynamics in polymers proposed by
      Cai et al. and, on that basis, discuss the physical origins of the local drag
      experienced by the nanoparticles in entangled polymer solutions.

PMID- 29192504
TI  - Utility of Fecal Calprotectin in Evaluation of Chronic Gastrointestinal Symptoms
      in Primary Care.
AB  - Fecal calprotectin (FC) is a marker of intestinal inflammation. Data are limited
      on utility of routine FC testing in pediatric primary care. Participants 0 to 18
      years old who had an FC test in the years 2010-2014 were retrospectively
      identified. Those with less than a year of follow-up or a prior diagnosis of
      inflammatory bowel disease (IBD) were excluded. In all, 84% (689/822) had normal
      FC; no participant with normal FC was diagnosed with IBD in the subsequent 12
      months. Also, 16% (133/822) had elevated FC, and 31% of those (42/133) were
      diagnosed with IBD. FC values for IBD and non-IBD groups were 1084 ug/g
      (interquartile range [IQR] = 514.4-2000) and 27.05 ug/g (IQR = 15.6-62.6; P <
      .001), respectively. Abdominal pain was the primary indication. In this cohort,
      sensitivity of FC for IBD is 100%, and specificity is 88%. The FC test can be an
      excellent tool in the primary care setting to exclude IBD and avoid unnecessary
      referrals and colonoscopies.

PMID- 29192505
TI  - US oncology-wide incidence, duration, costs and deaths from chemoradiation
      mucositis and antimucositis therapy benefits.
AB  - Approximate oncology-wide incidence, duration, costs and deaths associated with
      mucositis and identify health economic benefits of antimucositis therapies.
      Review the literature relevant to the clinical experience of mucositis by
      pathophysiology, incidence, duration, costs and deaths. Use US insurance
      actuarial and epidemiology on cancer to generalize an oncology-wide impact of
      toxic mucositis. Toxic mucositis causes oropharyngoesophageal ulcerations, chemo
      induced nausea, vomiting and diarrhea. Acutely, it lasts 102 days/six cycles of
      chemotherapy, 60 days in human stem-cell transplantation patients and 70-84 days
      in head and neck cancer patients at annual costs of US$13.23 billion/522,166
      treated patients (US$20,892/erosive-type mucositis patient, US$25,337/physiologic
      mucositis patient) and 46,699 deaths. Using antimucositis therapies prior to 2013
      provided fractional benefits at high costs. By completely preventing and rapidly
      reversing mucositis, high-potency polymerized cross-linked sucralfate promises
      superior health economic benefits.

PMID- 29192506
TI  - Extensive Hand Thermal and Blast Injury From Electronic Cigarette Explosion: A
      Case Report.
AB  - BACKGROUND: As the use of electronic cigarettes rises, more reports of injuries
      related to device explosion are surfacing. METHODS: Presented here is the case of
      a 35-year-old man sustaining extensive thermal and blast injuries to his hand
      when the device exploded while he was holding it. He required multiple surgeries
      involving groin flap coverage, tendon transfer, and nerve grafting to optimize
      his postinjury function. RESULTS: While much of his hand function has been
      restored, he has continued deficits in range of motion and sensation as a result
      of the incident. CONCLUSIONS: With increasing numbers of such injuries, hand
      surgeons must be aware of the blast mechanism involved so as to avoid missing
      deep soft tissue injury or disruption of deep structures, as demonstrated in this
      case.

PMID- 29192507
TI  - Effect of Transcranial Direct Current Stimulation in Patients With Tinnitus: A
      Meta-Analysis and Systematic Review.
AB  - OBJECTIVES: Subjective tinnitus is a phantom sensation experienced without any
      external source of sound that profoundly impacts the quality of life. Some
      investigations have claimed that transcranial direct current stimulation (tDCS)
      reduces tinnitus, but studies on tDCS have demonstrated variable results. This
      meta-analysis aimed to examine the effect of tDCS on patients with tinnitus.
      METHODS: We searched for articles published through January 5, 2016, in Medline,
      Cochrane, EMBASE, and Google Scholar using the following keywords: tinnitus,
      transcranial direct current stimulation, and tDCS. The study outcomes were change
      in magnitude estimates of loudness (loudness), tinnitus-related distress
      (distress), and Tinnitus Handicap Inventory (THI). RESULTS: Pooled results
      demonstrated that tDCS did not have a beneficial effect on loudness (pooled
      standardized difference in means = 0.674, 95% CI, -0.089 to 1.437, P = .083).
      Further, the pooled results demonstrated a greater reduction in distress for the
      tDCS group (pooled standardized difference in means = 0.634, 95% CI, 0.021-1.247,
      P = .043). CONCLUSIONS: We conclude that the pooled results demonstrated a
      greater reduction in distress for groups treated with tDCS as compared with those
      administered a sham treatment.

PMID- 29192508
TI  - Screening for Depression and Psychological Distress in a Currently Serving
      Military Population: The Diagnostic Accuracy of the K10 and the PHQ9.
AB  - This study is the first to examine the diagnostic accuracy of two depression
      screening scales-the Kessler Psychological Distress Scale (K10) and the Patient
      Health Questionnaire (PHQ)-in an entire regular-serving military population.
      Currently serving Australian Defence Force personnel ( n = 24,481) completed the
      K10 and PHQ9. Then a targeted subsample (i.e., the analysis sample, n = 1,730)
      completed a diagnostic interview to identify DSM-IV 30-day disorder. Weighted
      results represented the entire population ( N = 50,049). Both scales similarly
      showed a good ability to discriminate between personnel with and without
      depressive disorders. Optimal cutoffs (19 for K10, 6 for PHQ9) showed high
      sensitivity and good specificity, and were similar to though slightly lower than
      those recommended in civilian populations. Both scales appear to be valid screens
      for depressive disorder in the military, using the cutoffs identified. As both
      performed similarly, scale choice may depend on other factors (e.g., availability
      of norms).

PMID- 29192509
TI  - A Comparison of Removal Rates of Headless Screws Versus Headed Screws in
      Calcaneal Osteotomy.
AB  - BACKGROUND: Calcaneal osteotomy has been used to successfully treat both valgus
      and varus hindfoot deformities. Pain associated with implanted hardware may lead
      to further surgical intervention for hardware removal. Headless screws have been
      used to reduce postoperative hardware-associated pain and accompanying hardware
      removal, but data proving their effectiveness in this regard is lacking. The
      purpose of this study is to compare the rates of removal of headed and headless
      screws utilized in calcaneal osteotomy. METHODS: We conducted a retrospective
      chart review of 74 patients who underwent calcaneal osteotomy between January
      2010 and December 2014. The cohort was divided into 2 groups by fixation method:
      a headed screw and a headless screw group. Bivariate associations between
      infection or hardware removal, and screw type, screw head width, gender, smoking
      status, alcohol, hypertension, diabetes, hyperlipidemia, age, and body mass index
      were assessed using t-tests and Fisher's exact/chi2 tests for continuous and
      discrete variables, respectively. RESULTS: Headed screws were removed more
      frequently than headless screws (P < .0001): 15 of 30 (50%) feet that received
      headed screws and 4 of 44 (9%) of feet that received headless screws underwent
      subsequent revision for screw removal. In all cases, screws were removed because
      of pain. The calcaneal union rate was 100% in both cohorts. CONCLUSION: The rate
      of screw removal in calcaneal osteotomies is significantly lower in patients who
      receive headless screws than in those receiving headed screws. LEVELS OF
      EVIDENCE: Level IV.

PMID- 29192510
TI  - Aflatoxin B1 detoxification by cell-free extracts of Rhodococcus strains.
AB  - Aflatoxin B1 (AFB1) produced by Aspergillus molds is a genotoxic and carcinogenic
      mycotoxin. For the elimination of mycotoxins from food and feed,
      biodetoxification can be a successful tool. The aim of this study was to reveal
      biodetoxification with the cell-free extracts of Rhodococcus erythropolis NI1 and
      Rhodococcus rhodochrous NI2, which have been already proved to detoxify AFB1.
      Extracellular matrices of cultures and also intracellular extracts were applied
      for detoxification. In both cases, media containing constitutively produced and
      AFB1-induced enzymes were tested, respectively. The pH tolerance of enzymes in
      the detoxification was examined at pH 7, 7.5, and 8. The remained genotoxicity
      was detected by SOS-Chromotest and the AFB1 concentration was measured by high
      performance liquid chromatography with fluorescence detection. In the
      extracellular matrix, no reduction of genotoxicity was observed. However,
      detoxification was completed by intracellular enzymes. In intracellular extracts
      of both strains, genotoxicity was ceased by the constitutive enzymes within 6 h
      but induced and constitutive enzymes collectively achieved this result within
      minutes. Moreover, total biodetoxification was observed at every pH adjustment.
      Analytical results confirmed >84% degradation potential in each sample. Our
      results indicate a uniquely fast way for the detoxification of AFB1 with
      intracellular enzymes of R. erythropolis NI1 and R. rhodochrous NI2.

PMID- 29192511
TI  - The Kinect Project: Group motion-based gaming for people living with dementia.
AB  - Engaging in enjoyable activities is an essential part of well-being, but people
      with dementia can find participation increasingly difficult. Motion-based
      technologies can provide meaningful engagement in a wide range of activities, but
      for people with dementia to take advantage of these devices requires a good
      understanding of how best to select and present these activities to this
      population. The objective of this study was to explore the use of motion-based
      technology (Xbox Kinect) as a group activity for people with dementia who attend
      adult day programmes. This qualitative study took place in an adult day programme
      for older adults with age-related challenges. Participants (n = 23) were observed
      while playing a digital bowling game presented on Xbox Kinect one hour per week
      for a period of 20 weeks, to capture naturalistic data. Field notes generated
      through observations were transcribed and analysed to identify emerging themes.
      The findings revealed three predominant themes which illustrate the potential of
      motion-based technology as a group activity for people with dementia who attend
      adult day programmes: (a) the importance of having a trained trainer, (b)
      learning versus mastery and (c) playing 'independently together'. People with
      dementia can learn to play games presented on motion-based technology and enjoy
      doing so. Furthermore, using the technology in a group setting fostered an
      encouraging and supportive environment which further contributed to the leisure
      experience. However, to be used most effectively, staff must be trained to set-up
      and interact with the technology, as well as introduce, teach and support people
      with dementia to use it.

PMID- 29192512
TI  - Assessing apathy in long-term care residents with dementia: Who should be the
      rater?
AB  - Background Apathy is prominent in persons with dementia and apathy assessment is
      challenging. It remains unclear who should conduct apathy assessments in long
      term care settings for residents with moderate to advanced dementia. The Apathy
      Evaluation Scale (AES) is a widely used instrument and its use for long-term care
      residents with dementia needs to be further established. This study explored the
      relationship among apathy assessments conducted by family and clinical caregivers
      using the original AES (AES-18) and the nursing home version (AES-10). Methods
      This study used a cross-sectional, descriptive design and enrolled 15 quartets of
      participants recruited from long-term care settings. Each quartet consisted of
      one resident with dementia, one family member, one certified nursing assistant,
      and one licensed practical nurse or activity staff. Family, certified nursing
      assistants, and licensed practical nurses/activity staff rated the resident's
      apathy level on the AES independently. Bivariate Pearson correlation coefficients
      were used for analysis. Results The results revealed that ratings conducted by
      certified nursing assistants and licensed practical nurses/activity staff were
      moderately correlated for the AES-18 and the result approached statistical
      significance (r = 0.47, p = .08). None of the other AES ratings among family,
      certified nursing assistants, and licensed practical nurses/activity staff were
      significantly correlated. Discussion Family and clinical caregivers were
      incongruent on their AES ratings of apathy. It remains undetermined which rater
      provides the most valid AES rating for residents with dementia. Findings from
      this study further highlight challenges in rating apathy in this population.
      Future research is needed to determine best practices for accurate apathy
      assessment for residents with dementia in long-term care.

PMID- 29192513
TI  - Medication and care in Alzheimer's patients in the acute care setting: A
      qualitative analysis.
AB  - The acute hospital admission of patients with dementia is associated with poor
      outcome and higher costs. Much of our knowledge on how hospital stays are
      experienced by patients and staff is generated from short and fragmented data
      collections, in which the significance of knowledge about day-to-day care might
      be overlooked, and might partly explain why the poor outcome for this group of
      patients is not fully understood. This study used participant observation to
      follow patients with Alzheimer's disease admitted to orthopaedic wards after fall
      incidents. To gather longitudinal data, patients were followed during day and
      evening shifts, from admission to discharge. The data were interpreted from a
      phenomenological-hermeneutic perspective, inspired by Ricoeur's interpretation
      theory. The data showed that, despite having little specific knowledge about
      dementia care, staff were able to gather information about the patient's needs
      and wishes relevant to administrating medicine in a person-centred way. However,
      much of this valuable information was lost between shifts or became hidden among
      the overwhelming amount of information in electronic patient records. As a
      consequence, much of the knowledge about individual patients' needs and wishes
      had to be collected all over again at every shift. The study concludes that
      careful handover of information on person-centred dementia care can play an
      important role in making hospital stays more dementia-friendly.

PMID- 29192514
TI  - Iranian relatives' attitudes towards culturally profiled nursing homes for
      individuals living with dementia.
AB  - This article discusses Iranian family members' attitudes towards the culturally
      profiled nursing home, their relationships with the staff, the obstacles, their
      hopes and their fears. This study is based on qualitative research using 29 semi
      structured interviews with family members who had previously been informal
      caregivers, as well as using fieldwork, all in the same nursing home. The
      interviews were analysed by the three steps of content analysis. The results show
      the identification of three main categories with nine main subcategories. The
      categories and subcategories in the table clarify and explain how the
      interviewees tended to compare the situation in Iran with that in Sweden, how
      they perceived the situation in Sweden and finally how they also saw the
      culturally profiled nursing home.

PMID- 29192515
TI  - Welcome to the 10th volume of Epigenomics.

PMID- 29192516
TI  - Knockdown of angiopoietin-like 2 mimics the benefits of intermittent fasting on
      insulin responsiveness and weight loss.
AB  - Angiopoietin-like 2 (ANGPTL2) is an inflammatory adipokine linking obesity to
      insulin resistance. Intermittent fasting, on the other hand, is a lifestyle
      intervention able to prevent obesity and diabetes but difficult to implement and
      maintain. Our objectives were to characterize a link between ANGPTL2 and
      intermittent fasting and to investigate whether the knockdown of ANGPTL2
      reproduces the benefits of intermittent fasting on weight gain and insulin
      responsiveness in knockdown and wild-type littermates mice. Intermittent fasting,
      access to food ad libitum once every other day, was initiated at the age of three
      months and maintained for four months. Intermittent fasting decreased by 63% (p <
      0.05) gene expression of angptl2 in adipose tissue of wild-type mice. As
      expected, intermittent fasting improved insulin sensitivity (p < 0.05) and
      limited weight gain (p < 0.05) in wild-type mice. Knockdown mice fed ad libitum,
      however, were comparable to wild-type mice following the intermittent fasting
      regimen: insulin sensitivity and weight gain were identical, while intermittent
      fasting had no additional impact on these parameters in knockdown mice. Energy
      intake was similar between both wild-type fed intermittent fasting and ANGPTL2
      knockdown mice fed ad libitum, suggesting that intermittent fasting and knockdown
      of ANGPTL2 equally lower feeding efficiency. These results suggest that the
      reduction of ANGPTL2 could be a useful and promising strategy to prevent obesity
      and insulin resistance, although further investigation of the mechanisms linking
      ANGPTL2 and intermittent fasting is warranted. Impact statement Intermittent
      fasting is an efficient diet pattern to prevent weight gain and improve insulin
      sensitivity. It is, however, a difficult regimen to follow and compliance is
      expected to be very low. In this work, we demonstrate that knockdown of ANGPTL2
      in mice fed ad libitum mimics the beneficial effects of intermittent fasting on
      weight gain and insulin sensitivity in wild-type mice. ANGPTL2 is a cytokine
      positively associated with fat mass in humans, which inactivation in mice
      improves resistance to a high-fat metabolic challenge. This study provides a
      novel pathway by which IF acts to limit obesity despite equivalent energy intake.
      The development of a pharmacological ANGPTL2 antagonist could provide an
      efficient tool to reduce the burden of obesity.

PMID- 29192517
TI  - Applying the methodology of Design of Experiments to stability studies: a Partial
      Least Squares approach for evaluation of drug stability.
AB  - The aim of the present research is to show that the methodology of Design of
      Experiments can be applied to stability data evaluation, as they can be seen as
      multi-factor and multi-level experimental designs. Linear regression analysis is
      usually an approach for analyzing stability data, but multivariate statistical
      methods could also be used to assess drug stability during the development phase.
      Data from a stability study for a pharmaceutical product with hydrochlorothiazide
      (HCTZ) as an unstable drug substance was used as a case example in this paper.
      The design space of the stability study was modeled using Umetrics MODDE 10.1
      software. We showed that a Partial Least Squares model could be used for a multi
      dimensional presentation of all data generated in a stability study and for
      determination of the relationship among factors that influence drug stability. It
      might also be used for stability predictions and potentially for the optimization
      of the extent of stability testing needed to determine shelf life and storage
      conditions, which would be time and cost-effective for the pharmaceutical
      industry.

PMID- 29192518
TI  - In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban
      immediate-release tablets applying in silico data.
AB  - OBJECTIVE: This study aimed to develop and validate an in vitro dissolution
      method based on in silico-in vivo data to determine whether an in vitro-in vivo
      relationship could be established for rivaroxaban in immediate-release tablets.
      SIGNIFICANCE: Oral drugs with high permeability but poorly soluble in aqueous
      media, such as the anticoagulant rivaroxaban, have a major potential to reach a
      high level of in vitro-in vivo relationship. Currently, there is no study on
      scientific literature approaching the development of RIV dissolution profile
      based on its in vivo performance. METHODS AND RESULTS: Drug plasma concentration
      values were modeled using computer simulation with adjustment of pharmacokinetic
      properties. Those values were converted into drug fractions absorbed by the
      Wagner-Nelson deconvolution approach. Gradual and continuous dissolution of RIV
      tablets was obtained with a 30 rpm basket on 50 mM sodium acetate +0.2% SDS, pH
      6.5 medium. Dissolution was conducted for up to 180 min. The fraction absorbed
      was plotted against the drug fraction dissolved, and a linear point-to-point
      regression (R2 = 0.9961) obtained. CONCLUSION: The in vitro dissolution method
      designed promoted a more convenient dissolution profile of RIV tablets, whereas
      it suggests a better relationship with in vivo performance.

PMID- 29192519
TI  - Defining interdisciplinary competencies for audiological rehabilitation: findings
      from a modified Delphi study.
AB  - OBJECTIVES: The aim of this study is to derive a consensus on an
      interdisciplinary competency framework regarding a holistic approach for
      audiological rehabilitation (AR), which includes disciplines from medicine,
      engineering, social sciences and humanities. DESIGN: We employed a modified
      Delphi method. In the first round survey, experts were asked to rate an initial
      list of 28 generic interdisciplinary competencies and to propose specific
      knowledge areas for AR. In the second round, experts were asked to reconsider
      their answers in light of the group answers of the first round. STUDY SAMPLE: An
      international panel of 27 experts from different disciplines in AR completed the
      first round. Twenty-two of them completed the second round. RESULTS: We developed
      a competency framework consisting of 21 generic interdisciplinary competencies
      grouped in five domains and nine specific competencies (knowledge areas) in three
      clusters. Suggestions for the implementation of the generic competencies in
      interdisciplinary programmes were identified. CONCLUSIONS: This study reveals
      insights into the interdisciplinary competencies that are unique for AR. The
      framework will be useful for educators in developing interdisciplinary programmes
      as well as for professionals in considering their lifelong training needs in AR.

PMID- 29192520
TI  - Emerging data on improving response to hormone therapy: the role of novel
      targeted agents.
AB  - INTRODUCTION: Hormone receptor positive (HR+) breast cancer represents the most
      common subtype of breast cancer. Metastatic HR+ breast cancer may develop
      resistance to standard hormone therapies, arising from genomic alterations in the
      estrogen receptor and/or upregulation of other signal transduction pathways.
      Areas covered: In this review, we discuss hormone resistance and strategies to
      overcome it, from the pre-clinical and clinical perspectives. This review
      includes a discussion of inhibition of the PI3K/AKT/mTOR, CDK 4/6, histone
      deacetylation, fibroblast growth factor receptor, and immune pathways, based on
      review of relevant literature. Expert commentary: Several emerging novel
      therapies to improve the response to hormone therapy are approved or are in
      development. The most promising agents at present are inhibitors of CDK 4/6 and
      mTOR, which have already been incorporated into treatment in the advanced stage
      setting and are under study for early stage disease.

PMID- 29192521
TI  - High efficiency dry coating of non-subcoated pellets for sustained drug release
      formulations using amino methacrylate copolymers.
AB  - Dry coating utilizing a fluidized bed was evaluated in order to produce films
      with sustained drug release using amino methacrylate copolymers as film former.
      In contrast to other dry coating procedures using amino methacrylate copolymers,
      the described method enables an appropriate polymer adhesion by the selection of
      a plasticizer additive mixture in combination with the use of a three-way nozzle
      for simultaneous application. Well spreading fatty acid esters were found to
      increase the coating efficiency from 73% to approximately 86%, when they were
      used in conjunction with the plasticizer. Pellets were used as drug cores without
      previous treatment. After a curing step at 55  degrees C, the pellets exhibited a
      prolongation of the drug release over a period of about 6 h. Mainly the three
      parameters, coating level, composition of the polymers in the coating mixture,
      and the type of plasticizer, were found to exert distinct influence on the
      dissolution profile. Despite the differences in the coating procedure, the
      dissolution profiles of the coated pellets as well as the influencing parameters
      were similar to those known from conventional coating techniques.

PMID- 29192522
TI  - Chemical partitioning of fine particle-bound As, Cd, Cr, Ni, Co, Pb and
      assessment of associated cancer risk due to inhalation, ingestion and dermal
      exposure.
AB  - The bioavailability and human health risks of As, Pb, Ni, Co, Cr and Cd in fine
      particulate matter (PM2.5) at an urban site on a National highway in Agra, India
      were investigated. Inductively coupled plasma-optical emission spectrometer was
      used for metal analysis in sequentially extracted samples to ascertain the highly
      mobile, reducible, bioavailable and immobile fractions of the metals. Cancer risk
      resulting from inhalation, dermal and ingestion exposure to each metal in these
      fractions was calculated according to US EPA models. The average mass
      concentration of PM2.5 was 87.16 +/- 62.51 MUg/m3. Cr, Ni and Pb were the most
      abundant metals. The results showed that Pb and Cr were higher in the mobile
      fraction. Cd and Co had high bioavailability. Ingestion is the major exposure
      pathway for all heavy metals except Cr to infants, children and adults followed
      by inhalation and dermal contact. The cumulative risk for Cr(VI) due to dermal
      and inhalation routes exceed the maximum acceptable limit for children of age 1-7
      years, 8-15 years and adults when total concentration is considered, but the
      estimated risks are within the acceptable limit when the bioavailable, water
      soluble and mobile fraction are taken into account. Hence the study shows that
      children and adults living in the vicinity of this site are more susceptible,
      hence more attention should be paid to protect them from pollution hazards. The
      study indicates the importance of metal speciation in assessing associated human
      health risks.

PMID- 29192523
TI  - Suicide clusters among young Kenyan men.
AB  - Suicide is a leading cause of global mortality. Suicide clusters have recently
      been identified among peer networks in high-income countries. This study
      investigates dynamics of suicide clustering within social networks of young Kenya
      men ( n = 532; 18-34 years). We found a strong, statistically significant
      association between reported number of friends who previously attempted suicide
      and present suicide ideation (odds ratio = 1.9; 95% confidence interval (1.42,
      2.54); p < 0.001). This association was mediated by lower collective self-esteem
      (23% of total effect). Meaning in life further mediated the association between
      collective self-esteem and suicide ideation. Survivors of peer suicide should be
      evaluated for suicide risk.

PMID- 29192524
TI  - Problematic gaming behaviour and health-related outcomes: A systematic review and
      meta-analysis.
AB  - This systematic review and meta-analysis aimed to investigate the interplay
      between problematic gaming behaviour and health-related outcomes at different
      developmental stages. A total of 50 empirical studies met the specified inclusion
      criteria, and a meta-analysis using correlation coefficients was used for the
      studies that reported adverse health implications regarding the impact of
      problematic gaming behaviour on depression, anxiety, obsessive-compulsive
      disorder and somatisation. Overall, the results suggested that problematic gaming
      behaviour is significantly associated with a wide range of detrimental health
      related outcomes. Finally, the limitations of this review alongside its
      implications were discussed and considered for future research.

PMID- 29192525
TI  - Caring for musicians' ears: insights from audiologists and manufacturers reveal
      need for evidence-based guidelines.
AB  - OBJECTIVE: This study investigated clinical care delivered to musicians in
      Australia by audiologists and manufacturers of musicians' hearing protectors
      (MHP). DESIGN: Audiologists with experience treating musicians were invited to
      complete a survey on their service delivery. A second survey was administered to
      manufacturers of MHPs. STUDY SAMPLE: Four manufacturers of MHP and 31
      audiologists completed the surveys. Post hoc analyses were performed comparing
      the responses of audiologists with more versus less clinical experience; and
      those with and without musical training. RESULTS: There was considerable
      variation in the audiological care provided to musicians. Only one-third of
      audiologists performed pure-tone audiometry prior to MHP fitting, and there was
      little consistency across the sample in relation to impression taking, preferred
      attenuation or selection of canal length. There was also significant variation in
      the manufacturers' approach to MHP, each of whom provided different
      recommendations regarding preferred impression techniques and material viscosity.
      CONCLUSIONS: The results of this study reveal lack of consistency across the
      hearing healthcare sector with respect to care of musicians' hearing, with
      potential to impact upon the satisfaction with, and usage of, MHP. There is need
      for evidence-based, best practice guidelines and training to support clinical
      audiologists in providing optimal care.

PMID- 29192526
TI  - Intelligence Assessment Instruments in Adult Prison Populations: A Systematic
      Review.
AB  - Detection of intellectual disability (ID) in the penitentiary system is important
      for the following reasons: (a) to provide assistance to people with ID in
      understanding their legal rights and court proceedings; (b) to facilitate
      rehabilitation programs tailored to ID patients, which improves the enhancement
      of their quality of life and reduces their risk of reoffending; and (c) to
      provide a reliable estimate of the risk of offence recidivism. It requires a
      short assessment instrument that provides a reliable estimation of a person's
      intellectual functioning at the earliest possible stage of this process. The aim
      of this systematic review is (a) to provide an overview of recent short
      assessment instruments that provide a full-scale IQ score in adult prison
      populations and (b) to achieve a quality measurement of the validation studies
      regarding these instruments to determine which tests are most feasible in this
      target population. The Preferred Reporting Items for Systematic reviews and Meta
      Analyses Statement is used to ensure reliability. The Satz-Mogel, an item
      reduction short form of the Wechsler Adult Intelligence Scale, shows the highest
      correlation with the golden standard and is described to be most reliable.
      Nevertheless, when it comes to applicability in prison populations, the shorter
      and less verbal Quick Test can be preferred over others. Without affecting these
      conclusions, major limitations emerge from the present systematic review, which
      give rise to several important recommendations for further research.

PMID- 29192527
TI  - Comments on "Empirical Antibiotic Treatment in Diabetic Foot Infection: A Study
      Focusing on the Culture and Antibiotic Sensitivity in a Population From Southern
      China".

PMID- 29192528
TI  - Hospitalization costs and resource allocation in cholecystectomy with use of
      intravenous versus oral acetaminophen.
AB  - OBJECTIVE: To evaluate intravenous (IV) acetaminophen (APAP) vs oral APAP use as
      adjunctive analgesics in cholecystectomy patients by comparing associated
      hospital length of stay (LOS), hospital costs, opioid use, and rates of
      nausea/vomiting, respiratory depression, and bowel obstruction. METHODS: We
      conducted a retrospective analysis of the Premier Database (January 2012 to
      September 2015) including cholecystectomy patients who received either IV APAP or
      oral APAP. Differences in LOS, hospitalization costs, mean daily morphine
      equivalent dose (MED), and potential opioid-related adverse events were
      estimated. Multivariable logistic regression was performed for the binary
      outcomes and instrumental variable regressions, using the quarterly rate of IV
      APAP use for all hospitalizations by hospital as the instrument in two-stage
      least squares regressions for continuous outcomes. Models were adjusted for
      patient demographics, clinical risk factors, and hospital characteristics.
      RESULTS: Among 61,017 cholecystectomy patients, 31,133 (51%) received IV APAP.
      Subjects averaged 51 and 57 years of age, respectively, in the IV and oral APAP
      cohorts. In the adjusted models, IV APAP was associated with 0.42 days shorter
      LOS (95% CI = -0.58 to -0.27; p < .0001), $1,045 lower hospitalization costs (95%
      CI = -$1,521 to -$569; p < .0001), 2 mg lower average daily MED (95% CI = -3 mg
      to -0.9 mg; p = .0005), and lower rates of respiratory depression (odds ratio
      [OR] = 0.89, 95% CI = 0.82-0.97; p = .006), and nausea and vomiting (OR = 0.86,
      95% CI = 0.86-0.86; p < .0001). CONCLUSIONS: In patients having cholecystectomy,
      the addition of IV APAP to perioperative pain management is associated with
      shorter LOS, lower costs, reduced opioid use, and less frequent nausea/vomiting
      and respiratory depression compared to oral APAP. These findings should be
      confirmed in a prospective study comparing IV and oral APAP.

PMID- 29192529
TI  - Impact of measures to control brucellosis on disease characteristics in humans:
      experience from an endemic region in the Balkans.
AB  - AIM: To analyze the impact of measures undertaken to control brucellosis in the
      Republic of Macedonia on demographic, epidemiological and clinical
      characteristics of the disease in humans. METHODS: Demographic, epidemiological
      and clinical characteristics of 340 patients with brucellosis were
      retrospectively analyzed. Patients were treated at the University Clinic of
      Infectious Diseases in Skopje during three time periods: 1989-1990 when no
      national strategy for disease control existed, 2000-2001 when some activities for
      control were performed and 2011-2014 when an organized and financially supported
      strategy was accomplished. RESULTS: A drastic decrease of the number of cases of
      human brucellosis during the last period when compared to the first two ones (3.9
      and 3.3 times lower, respectively) was evident. Patients from the third period
      were significantly older, with median age 41 years (range 4-73) vs. 31 years (3
      77) and 34 years (1-74), respectively (p = .013). There were more males (86.6 vs.
      73.6% and 63.2%, respectively, p = .002) and the disease was more often acquired
      professionally (80.6 vs. 60.1% and 59.2%, respectively, p = .006). Fewer patients
      from the third period had elevated body temperature either as a symptom (50.7 vs.
      73.6% and 69.6%, respectively, p = .003), or as a sign (35.8 vs. 55.4% and 56.8%,
      respectively, p = .011) and less often exhibited focal forms (40.3 vs. 56.8% and
      64.0%, respectively, p = .007). CONCLUSION: The national strategy for brucellosis
      control, which included vaccination of small ruminants, resulted in a decrease of
      human brucellosis cases in the Republic of Macedonia and there was a tendency to
      milder disease manifestations.

PMID- 29192530
TI  - Cost-effectiveness analysis of infliximab, adalimumab, golimumab and vedolizumab
      for moderate to severe ulcerative colitis in Spain.
AB  - OBJECTIVES: Assess the efficiency of biologic treatment for moderate to severe
      ulcerative colitis (UC) which are indicated and financed for this pathology by
      Spain. METHODS: A Markov model was constructed to simulate the progression in a
      cohort of patients with moderate to severe UC. The perspective chosen was
      National Health Service with an over 10 years of time horizon, with a discount
      rate of 3%, and established threshold of ?30,000/quality-adjusted life-year
      (QALY). RESULTS: The comparison between infliximab versus adalimumab achieved an
      incremental cost-effectiveness ratio (ICER) of ?45,582/QALY, with a 0.900 QALYs
      difference of efficacy and an incremental cost of ?41,036. Golimumab versus
      adalimumab reached an ICER of ?2,175,992/QALY, with a difference of 0.001 QALY in
      efficacy and a raising cost to ?2,611. The comparison between vedolizumab with
      adalimumab achieved an ICER of ?90,532/QALY, 0.930 QALYs of difference and an
      increasing cost of ?84,218. The probabilistic sensitivity analysis shows that
      adalimumab would be cost-effective in the 65.2% of the simulations, infliximab in
      the 18.4%, golimumab in the 16.4% and vedulizumab for the 0%. CONCLUSIONS: Among
      all these drugs studied, adalimumab is the most cost-effective drug for the
      treatment of moderate to severe UC for a threshold of ?30,000/QALY in Spain.

PMID- 29192531
TI  - Comparison of acute to chronic ratios between silver and gold nanoparticles,
      using Ceriodaphnia dubia.
AB  - As integration of nanoparticles (NPs) into products becomes more common, the need
      to address the paucity of chronic hazard information for aquatic environments
      required to determine risk potential increases. This study generated acute and
      chronic toxicity reference values for Ceriodaphnia dubia exposed to 20 and 100 nm
      silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) to generate and
      evaluate potential differences in acute-to-chronic ratios (ACR) using two
      different feeding methods. A modified feeding procedure was employed alongside
      the standard procedures to investigate the influence of food on organism
      exposure. An 8-h period before food was added allowed direct organism exposure to
      NP dispersions (and associated ions) without food-to-NP interactions. The AgNPs
      [chronic lethal median concentrations (LC50) between 18.7 and 31.9 ug/L] were
      substantially more toxic than AuNPs (LC50 = 21 507 to >26 384 ug/L). The modified
      chronic testing method resulted in greater sensitivity in AgNPs exposures.
      However, the modified feeding ration had less of an effect in exposures to the
      larger (100 nm) AgNPs compared to smaller particles (20 nm). The ACRs for AgNPs
      using the standard feeding ration were 1.6 and 3.5 for 20 nm and 100 nm,
      respectively. The ACRs for AgNPs using the modified feeding ration were 3.4 and
      7.6 for 20 nm and 100 nm NPs, respectively. This supports that the addition of
      the standard feeding ration decreases C. dubia chronic sensitivity to AgNPs,
      although it must also be recognized organisms may be sensitized due to less
      access to food. The ACRs for 20 nm and 100 nm AuNPs (standard ration only) were
      4.0 and 3.0, respectively. It is important to also consider that dissolved Ag+
      ions are more toxic than AgNPs, based on both acute toxicity values in the cited
      literature and chronic toxicity thresholds generated in this study that support
      existing thresholds that Ag+ are likely protective of AgNPs effects.

PMID- 29192532
TI  - Association between anti-tuberculosis drug resistance-conferring mutations and
      treatment outcomes in Myanmar.

PMID- 29192533
TI  - Cardiovascular mortality trends in non-Hodgkin's lymphoma: a population-based
      cohort study.
AB  - BACKGROUND: Non-Hodgkin's lymphoma (NHL) survivors are at a higher risk of
      cardiovascular diseases (CVDs). METHODS: A population-based study was conducted
      to investigate the cardiovascular mortality trends to identify NHL survivors at
      the highest risk. RESULTS: The CVDs mortality was the second most common cause of
      death (13.07%) after NHL. There were more patients >= 60 years old in the
      cardiovascular group (87.2%), P < 0.001. Patients who died from CVDs had the best
      survival while patients who died from NHL had a significantly lower mean
      survival. The overall survival rate was 92.4%. Consistently, older age,
      unmarried, male patients, not recently diagnosed with NHL and not receiving
      radiation and/or surgery were associated with a worse survival across all models.
      The black race and stage IV only had a worse cardiovascular specific survival
      (CVSS). CONCLUSIONS: Although the CVSS improved over time, the mortality from the
      CVDs is still the second most common cause of death after NHL. Older age, not
      married, black, male patients, not recently diagnosed with NHL, with an advanced
      stage and not receiving radiation and/or surgery were associated with a worse
      survival. Risk factor modification along with CVDs screening should be
      intensified in NHL patients with these mortality predictors.

PMID- 29192534
TI  - Intensive Communicative Therapy Reduces Symptoms of Depression in Chronic
      Nonfluent Aphasia.
AB  - BACKGROUND: Patients with brain lesions and resultant chronic aphasia frequently
      suffer from depression. However, no effective interventions are available to
      target neuropsychiatric symptoms in patients with aphasia who have severe
      language and communication deficits. OBJECTIVE: The present study aimed to
      investigate the efficacy of 2 different methods of speech and language therapy in
      reducing symptoms of depression in aphasia on the Beck Depression Inventory (BDI)
      using secondary analysis (BILAT-1 trial). METHODS: In a crossover randomized
      controlled trial, 18 participants with chronic nonfluent aphasia following left
      hemispheric brain lesions were assigned to 2 consecutive treatments: (1)
      intensive language-action therapy (ILAT), emphasizing communicative language use
      in social interaction, and (2) intensive naming therapy (INT), an utterance
      centered standard method. Patients were randomly assigned to 2 groups, receiving
      both treatments in counterbalanced order. Both interventions were applied for 3.5
      hours daily over a period of 6 consecutive working days. Outcome measures
      included depression scores on the BDI and a clinical language test (Aachen
      Aphasia Test). RESULTS: Patients showed a significant decrease in symptoms of
      depression after ILAT but not after INT, which paralleled changes on clinical
      language tests. Treatment-induced decreases in depression scores persisted when
      controlling for individual changes in language performance. CONCLUSIONS:
      Intensive training of behaviorally relevant verbal communication in social
      interaction might help reduce symptoms of depression in patients with chronic
      nonfluent aphasia.

PMID- 29192537
TI  - Journal of Neurosurgery's Top 25 highly cited articles on Gamma Knife surgery for
      meningioma.

PMID- 29192535
TI  - Prism Adaptation in Rehabilitation? No Additional Effects of Prism Adaptation on
      Neglect Recovery in the Subacute Phase Poststroke: A Randomized Controlled Trial.
AB  - BACKGROUND: Patients with neglect ignore or respond slower to contralesional
      stimuli. Neglect negatively influences independence in activities of daily living
      (ADL). Prism adaptation (PA) is one of the most frequently studied treatments,
      yet there is little evidence regarding positive effects on neglect behavior in
      ADL. OBJECTIVE: To assess whether PA in the subacute phase ameliorates neglect in
      situations of varying complexity. METHODS: A total of 70 neglect patients
      admitted for inpatient stroke rehabilitation received either PA or sham
      adaptation (SA) for 2 weeks, with full access to standard treatment. There were 7
      time-dependent measurements (baseline and 1-4, 6, and 14 weeks after start of
      treatment). The primary outcome was change of neglect as observed during basic
      ADL with the Catherine Bergego Scale (CBS). Secondary outcomes were changes in
      performance on a dynamic multitask (ie, the Mobility Assessment Course [MAC]) and
      a static paper-and-pencil task (ie, a shape cancellation task [SC]). RESULTS: In
      all, 34 patients received PA and 35 SA. There were significant time-dependent
      improvements in performance as measured with the CBS, MAC, and SC (all F > 15.57;
      P < .001). There was no significant difference in magnitude of improvement
      between groups on the CBS, MAC, and SC (all F < 2.54; P > .113]. CONCLUSIONS: No
      beneficial effects of PA over SA in the subacute phase poststroke were observed,
      which was comparable for situations of varying complexity. Heterogeneity of the
      syndrome, time post-stroke onset, and the content of treatment as usual are
      discussed. Basic knowledge on subtypes and recovery patterns would aid the
      development of tailored treatment.

PMID- 29192538
TI  - The Impact of a Childhood Cancer Diagnosis on the Children and Siblings' School
      Attendance, Performance, and Activities: A Qualitative Descriptive Study.
AB  - Families of children with cancer are confronted with unexpected out-of-pocket
      expenses and productivity costs associated with the diagnosis. One productivity
      cost that falls on children is the impact of cancer on children's school
      attendance, performance, and activities (eg, play, friendships, and
      socialization). Nested within the Childhood Cancer Cost Study, this qualitative
      descriptive study used convenience sampling to recruit and interview parents of
      children newly diagnosed with cancer. Content analysis techniques were used to
      inductively descriptive the semistructured interview data. Sixty-six parents of
      65 children with cancer and of 73 siblings participated. The most commonly
      reported productivity loss in children with cancer was school absenteeism mainly
      due to cancer treatment. Children fell behind their classmates academically and
      lost important social time with peers. A few siblings also fell behind their
      peers primarily due to limited parental attention. Parents adopted various
      strategies to lessen the impact of the diagnosis on their children's school
      attendance, performance, and activities. Providing parents with additional
      resources and support may optimize their children's academic and social
      reintegration into school.

PMID- 29192539
TI  - Experimental chronic cerebral hypoperfusion results in decreased pericyte
      coverage and increased blood-brain barrier permeability in the corpus callosum.
AB  - Murine chronic cerebral hypoperfusion (CCH) results in white matter (WM) injury
      and behavioral deficits. Pericytes influence blood-brain barrier (BBB) integrity
      and cerebral blood flow. Under hypoxic conditions, pericytes detach from
      perivascular locations increasing vessel permeability and neuronal injury. This
      study characterizes the time course of BBB dysfunction and pericyte coverage
      following murine experimental CCH secondary to bilateral carotid artery stenosis
      (BCAS). Mice underwent BCAS or sham operation. On post-procedure days 1, 3, 7 and
      30, corpus callosum BBB permeability was characterized using Evans blue (EB)
      extravasation and IgG staining and pericyte coverage/count was calculated. The
      BCAS cohort demonstrated increased EB extravasation on postoperative days 1 ( p =
      0.003) 3 ( p = 0.002), and 7 ( p = 0.001) when compared to sham mice. Further, EB
      extravasation was significantly greater ( p = 0.05) at day 3 than at day 30 in
      BCAS mice. BCAS mice demonstrated a nadir in pericyte coverage and count on post
      operative day 3 ( p < 0.05, compared to day 7, day 30 and sham). Decreased
      pericyte coverage/count and increased BBB permeability are most pronounced on
      postoperative day 3 following murine CCH. This precedes any notable WM injury or
      behavioral deficits.

PMID- 29192540
TI  - Thoracoabdominal breathing motion pattern and coordination of professional ballet
      dancers.
AB  - Ballet training includes exercises of high and moderate intensities, which
      require breathing control for a good performance. This study describes the
      thoracoabdominal motion of professional dancers and compares the breathing
      patterns between professional dancers and non-dancers. Participants of this study
      were four male and four female (30.33 +/- 4.64 years) professional dancers and
      four male and four female (22.75 +/- 1.49 years) non-dancers. The participants
      executed two breathing manoeuvres while sitting motionless: quiet breathing (QB)
      and vital capacity (VC). The 3D coordinates of 32 retro-reflective markers
      positioned on the trunk were used to calculate the volume of the superior thorax,
      inferior thorax and abdomen. Principal component analysis was applied in the
      volume variation of each trunk compartment to search for dominant independent
      variables in a breathing motion pattern. The correlation coefficient was
      calculated to verify the coordination between the compartments during the
      breathing manoeuvres. A predominance of the superior thorax or abdomen movement
      was found in both groups. The professional ballet dancers have an efficient
      breathing pattern and maintain the same breathing pattern in QB and VC
      manoeuvres. On the other hand, the non-dancers group showed relevant changes of
      the breathing pattern to respond to a greater breathing effort, like in VC.

PMID- 29192541
TI  - Chronic post-traumatic headache in children and adolescents: systematic review of
      prevalence and headache features.
AB  - The aim of this systematic review is to determine the prevalence and clinical
      features of chronic post-traumatic headache (CPTH) in children and adolescents.
      Literature search of PubMed, Embase, Cochrane databases and Google Scholar was
      carried out for all studies reporting on CPTH in children and young people under
      the age of 18 years between January 1980 and November 2016. Search command
      included post-traumatic headache, postconcussion syndrome, child and adolescent.
      Demographic data, diagnostic criteria of headache disorders, occurrence of
      headache after head injury and headache phenotypes were collected. The prevalence
      of nonspecific 'chronic headache' after head injury in children was 39% and
      prevalence of CPTH, as defined by the International Classification of Headache
      Disorders (2004), was 7.6% (95% CI: 5.9-9.7). Migraine-like headache was the most
      common presentation followed by tension-type headache. Other children had either
      mixed or unclassified headache disorders.

PMID- 29192542
TI  - The effects of a simulated occupational kneeling exposure on squat mechanics and
      knee joint load during gait.
AB  - Occupational kneeling is associated with an increased risk for tibiofemoral knee
      osteoarthritis. Forces on the knee in the kneeling posture, as well as the
      greater incidence of meniscus tears among workers, likely contribute to the
      increased risk. We hypothesise that an additional mechanism may contribute -
      altered neuromuscular control due to prolonged high knee flexion. Forty
      participants (20 male, 20 female) completed an evaluation of gait and squatting
      before, immediately following, and 30 min following a 30 min simulated
      occupational kneeling exposure. An increase in the peak external knee adduction
      moment and a delay in vastus medialis activation onset during walking were
      observed post-kneeling, as well as increased frontal plane knee motion during
      squatting. This was the first investigation to find changes in high flexion
      transitions as a result of kneeling. Greater frontal plane knee motion may
      increase the risk for meniscal tears, and subsequently, knee osteoarthritis.
      Practitioner Summary: A 30 min simulated occupational kneeling exposure resulted
      in small but significant gait changes. The greatest effect was on frontal plane
      knee movement during squatting, which is especially relevant to occupations
      requiring frequent kneeling/squatting. This increased motion may indicate an
      increased risk of injury, which supports a link to knee osteoarthritis.

PMID- 29192544
TI  - Daughters sense their mother's stress.

PMID- 29192545
TI  - Cardiovascular, respiratory and sedative effects of intramuscular alfaxalone,
      butorphanol and dexmedetomidine compared with ketamine, butorphanol and
      dexmedetomidine in healthy cats.
AB  - Objectives The aim of the study was to evaluate the cardiorespiratory effects,
      quality of sedation and recovery of intramuscular alfaxalone-dexmedetomidine
      butorphanol (ADB) and ketamine-dexmedetomidine-butorphanol (KDB), in cats.
      Methods Nine adult, healthy cats (6.63 +/- 1.42 kg) were enrolled in a blinded,
      randomized, crossover experimental design. Cats were sedated twice
      intramuscularly, once with ADB (alfaxalone 1 mg/kg, dexmedetomidine 0.005 mg/kg,
      butorphanol 0.2 mg/kg), and once with KDB (ketamine 5 mg/kg, dexmedetomidine
      0.005 mg/kg, butorphanol 0.2 mg/kg), in random order. Data collected included
      heart rate (HR), arterial blood pressure and blood gas analysis, respiratory rate
      and sedation score. Analysis of variance with Bonferroni post-hoc correction was
      used for parametric data, and a Wilcoxon signed rank test was used for non
      parametric data. Significance was set at P <0.05. Results Total sedation time was
      shorter for ADB (90.71 +/- 15.12 mins vs 147.00 +/- 47.75 mins). Peak sedation
      was observed within 15 mins in both groups. Quality of recovery was excellent in
      both groups. HR decreased over time in both groups. Diastolic and mean arterial
      pressure decreased over time for ADB, becoming significant after 30 mins. All
      cardiovascular variables were within the clinically acceptable range in both
      groups. Arterial partial pressure of oxygen was significantly decreased from
      baseline for KDB at all time points (73 +/- 2.5 mmHg [9.7 +/- 0.3 kPa] vs ADB 83
      +/- 2.6 mmHg [11 +/- 0.3 kPa]). Hypoventilation was not observed. Conclusions and
      relevance Both protocols produced acceptable cardiovascular stability. Sedation
      and recovery quality were good, albeit sedation was shorter with ADB. Although
      oxygenation was better maintained in the ADB group, all sedated cats should
      receive oxygen supplementation.

PMID- 29192546
TI  - Drip infusion cholangiography with CT in cats.
AB  - OBJECTIVES: Ultrasonography can detect extrahepatic biliary obstructions.
      However, visualisation of part of the bile duct using ultrasonography can be
      technically difficult if there is overlying bowel gas. This study investigated
      the safety and value of drip infusion cholangiography with computed tomography
      (DIC-CT) in the visualisation of the bile duct in healthy cats and extrahepatic
      biliary obstruction in cats with cholelithiasis. METHODS: DIC-CT was performed in
      three healthy cats and two cats with cholelithiasis. Meglumine iotroxate was
      administered by intravenous drip infusion over 30 mins. The attenuation value was
      measured perpendicular to the lumen by a region of interest covering about 50% of
      the area of the lumen. RESULTS: The bile ducts were visualised successfully with
      DIC-CT in all healthy cats without any significant adverse events. The
      attenuation value of the contrast medium was 271 +/- 37 HU. In the two cats with
      cholelithiasis, the presence or absence of extrahepatic biliary obstruction was
      determined using DIC-CT without any significant adverse events. The attenuation
      value of cholelithiasis in the cat with an extrahepatic biliary obstruction was
      933 +/- 119 HU. In the cat with no extrahepatic biliary obstruction, the
      attenuation value of the contrast medium was 249 +/- 53 HU and the attenuation
      value of cholelithiasis was 167 +/- 28 HU. CONCLUSIONS AND RELEVANCE: DIC-CT
      visualises bile ducts and detects obstructive biliary disease without significant
      adverse events. Therefore, it appears to be a safe procedure for visualisation of
      the bile duct in cats.

PMID- 29192547
TI  - Finding Salmonella in unusual sites: look before you leap. A case series.

PMID- 29192548
TI  - In vivo study on biodegradable magnesium alloys: Bone healing around WE43 screws.
AB  - Introduction A standard osteosynthetic material for maxillofacial skeleton is
      titanium and its alloys. The convenience of degradable material is avoiding of
      second surgery in cases, where removal of the material is necessary. Magnesium
      biodegradable alloys have similar mechanic properties as cortical bone -
      reasonable corrosion and sufficient biologic properties. They might be used in
      facial skeleton fixation. Materials and methods The study included a total of 16
      rabbits, and they were randomly divided into two groups. Each group received two
      screws (WE4 and titanium as a standard material) in artificially drilled defect
      into right tibia. Animals were euthanized at four-week intervals. Bone samples
      with implants underwent microfocus CT scans and were histologically examined.
      Results WE43 alloys showed fragmentation of the material on the 16th week -
      statistically significant volume loss was found between weeks 12 and 16. Bone
      healing around the WE43 screws was of similar quality as around titanium screws,
      and no adverse effect was noticed. Conclusion The study showed good quality of
      bone healing around WE43 implants. From this point of view, the WE43 alloy meets
      the requirements of osteosynthetic material for maxillofacial skeleton.

PMID- 29192549
TI  - A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an
      Amphetamine Extended-Release Oral Suspension in Healthy Adults.
AB  - OBJECTIVE: The purpose of this study was to compare the pharmacokinetics of a new
      extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended
      release mixed amphetamine salts product, Adderall XR(r). METHOD: In this single
      dose, open-label, randomized, two-period, two-treatment crossover study, 42
      healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg
      Adderall XR capsule in another period (both containing 18.8 mg of amphetamine
      base) under fasted conditions. Blood samples were analyzed for d- and l
      amphetamine concentrations, and pharmacokinetic parameters Cmax, AUC0-5, AUC5
      last, and AUCinf were calculated to determine bioequivalence. Safety was
      monitored throughout the study. RESULTS: The 90% confidence intervals (CIs) for
      the log-transformed Cmax, AUC0-5, AUC5-last, and AUCinf fell within the accepted
      80% to 125% range for establishing bioequivalence for d- and l-amphetamine. The
      most common adverse events were nausea and decreased appetite. CONCLUSION: AMP XR
      OS is bioequivalent to Adderall XR in healthy adult participants.

PMID- 29192550
TI  - Kinematic analysis of proximal-to-distal and simultaneous motion sequencing of
      straight punches.
AB  - Consecutive proximal-to-distal sequencing of motion is considered to be integral
      for generating high velocity of distal segments in many sports. Simultaneous
      usage of proximal and distal segments as seen in martial arts is by far less well
      investigated. Therefore, the aim of the study was to characterise and
      differentiate the concepts of consecutive (CSM) and simultaneous (SSM) sequence
      of motion in straight reverse punches as practised in Practical Wing Chun. Four
      experienced martial artists succeeded an eligibility test for technical
      proficiency in both concepts and performed a total number of 20 straight punches
      per concept. Eight MX13 Vicon cameras (250 fps) and Visual3D were used for motion
      capture and analyses. Both motion concepts showed proximal-to-distal sequencing
      of maximal joint velocities but, in SSM, this was coupled with simultaneous
      initiation. Key characteristics were: high pelvis momentum and backswing of
      shoulder and elbow (CSM); and importance of shoulder involvement (SSM). Different
      ranges of motion, timing aspects and achieved maximal angular velocities
      distinguished both concepts, which led to differences (p < 0.05) in fist velocity
      at contact, execution time, distance and horizontal shift of the centre of mass.
      Proper application of both concepts depends on the environmental setting,
      situational requirements and individual fighting style.

PMID- 29192551
TI  - Parent-child attachment: meta-analysis of associations with parenting behaviors
      in middle childhood and adolescence.
AB  - Maternal sensitivity predicts mother-child attachment in young children, but no
      meta-analysis has investigated the link between parenting and parent-child
      attachment in older children. This study examined the relationship between parent
      child attachment and multiple components of parenting in children 5-18 years of
      age. A series of meta-analyses showed that parents of children with more secure
      attachment are more responsive, more supportive of the child's autonomy, use more
      behavioral control strategies, and use less harsh control strategies. Parents of
      children with more avoidant attachment were less responsive and used less
      behavioral control strategies. Ambivalent attachment was not significantly
      related to any of the parenting behaviors, and there were not enough studies to
      reliably test the relationship between disorganized attachment and parenting.
      There were few significant moderators. The findings inform new areas for future
      research, as well as family interventions for at-risk youth.

PMID- 29192553
TI  - The Mid-Victorian period and the Astronomical Register (1863-1886): 'A medium of
      communication for amateurs and others'.

PMID- 29192552
TI  - Polymorphisms associated with adalimumab and infliximab response in moderate-to
      severe plaque psoriasis.
AB  - AIM: This study evaluated the influence of pharmacogenetics in psoriatic patients
      treated with adalimumab and/or infliximab. MATERIALS & METHODS: Prospective
      observational study evaluating the association of 124 polymorphisms with the
      response to adalimumab or infliximab (PASI75) in patients with moderate-to-severe
      plaque psoriasis at 3 months (n = 95) and 6 months of treatment (n = 90).
      Significant SNPs for univariate analysis were subjected to multivariate analysis.
      RESULTS: Five SNPs were associated with PASI75 at 3 months: rs6661932 (IVL),
      rs2546890 (IL-12B), rs2145623 (NFKBIA), rs9304742 (ZNF816A) and rs645544
      (SLC9A8). Furthermore, rs1061624 (TNFR1B) was associated with PASI75 at 6 months.
      CONCLUSION: Nevertheless, these biomarkers should be validated in large-scale
      studies before implementation in clinical practice.

PMID- 29192554
TI  - Prognostic significance of Ki67 and its correlation with mitotic index in dogs
      with diffuse large B-cell lymphoma treated with 19-week CHOP-based protocol.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in
      dogs. We evaluated Ki67 immunoexpression and mitotic index (MI) in dogs diagnosed
      with DLBCL and treated with a 19-wk CHOP (cyclophosphamide, doxorubicin,
      vincristine, and prednisone) protocol. Twenty-nine lymph node samples from dogs
      diagnosed with DLBCL were analyzed for Ki67 immunostaining, and positive cells
      present in 1 cm2 were counted in a grid reticle for comparison of survival times
      above and below the means. The Ki67 mean was 107, and the MI mean was 21. There
      was a significant ( p < 0.05) difference in median survival time between Ki67
      immunostaining above and below the mean, with no difference in MI groups. Ki67
      values >107 positive cells per 5 HPF counted in a grid reticle were associated
      with shorter survival times in dogs with DLBCL treated with a 19-wk CHOP-based
      protocol.

PMID- 29192555
TI  - Nanoemulsions of sulfonamide carbonic anhydrase inhibitors strongly inhibit the
      growth of Trypanosoma cruzi.
AB  - Sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors targeting the alpha
      class enzyme from the protozoan pathogen Trypanosoma cruzi, responsible of Chagas
      disease, were recently reported. Although many such derivatives showed low
      nanomolar activity in vitro, they were inefficient anti-T. cruzi agents in vivo.
      Here, we show that by formulating such sulfonamides as nanoemulsions in clove
      (Eugenia caryophyllus) oil, highly efficient anti-protozoan effects are observed
      against two different strains of T. cruzi. These effects are probably due to an
      enhanced permeation of the enzyme inhibitor through the nanoemulsion formulation,
      interfering in this way with the life cycle of the pathogen either by inhibiting
      pH regulation or carboxylating reactions in which bicarbonate/CO2 are involved.
      This type of formulation of sulfonamides with T. cruzi CA inhibitory effects may
      lead to novel therapeutic approaches against this orphan disease.

PMID- 29192557
TI  - Message from the editor: welcome to the 10th volume of Immunotherapy.

PMID- 29192558
TI  - Spleen tyrosine kinase inhibition: a new promising approach to chronic and
      refractory immune thrombocytopenia.

PMID- 29192556
TI  - Bacterial endotoxin (lipopolysaccharide) binds to the surface of gold
      nanoparticles, interferes with biocorona formation and induces human monocyte
      inflammatory activation.
AB  - Nanoparticles (NPs) are easily contaminated by bacterial endotoxin
      (lipopolysaccharide [LPS]). The presence of LPS can be responsible for many
      immune/inflammatory effects attributed to NPs. In this study, we examined the
      effects of LPS adsorption on the NP surface on the formation of a biocorona in
      biological fluids and on the subsequent inflammation-inducing activity of NPs.
      Different gold (Au) NPs with sizes ranging from 10 to 80 nm and with different
      surface functionalization (sodium citrate, lipoic acid, and branched
      polyethyleneimine (BPEI), or polyethylene glycol (PEG)) were exposed to E. coli
      LPS under different conditions. The binding capacity of LPS to the surface of
      AuNPs was dose- and time-dependent. LPS attached to sodium citrate and lipoic
      acid coatings, but did not adhere to BPEI- or PEG-coated NPs. By computational
      simulation, the binding of LPS to AuNPs seems to follow the Langmuir absorption
      isotherm. The presence of LPS on AuNP surface interfered and caused a decrease in
      the formation of the expected biomolecular corona upon incubation in human
      plasma. LPS-coated AuNPs, but not the LPS-free NPs, induced significant
      inflammatory responses in vitro. Notably, while free LPS did also induce an anti
      inflammatory response, LPS bound to NPs appeared unable to do so. In conclusion,
      the unintentional adsorption of LPS onto the NP surface can affect the biocorona
      formation and the inflammatory properties of NPs. Thus, for an accurate
      interpretation of NP interactions with cells, it is extremely important to be
      able to distinguish the intrinsic NP biological effects from those caused by
      biologically active contaminants such as endotoxin.

PMID- 29192559
TI  - A refined and translationally relevant model of chronic DSS colitis in BALB/c
      mice.
AB  - Inflammatory bowel diseases (IBD) are chronic relapsing disorders of the
      gastrointestinal tract. Several mouse models for IBD are available, but the acute
      dextran sulfate sodium (DSS)-induced colitis model is mostly used for preclinical
      studies. However, this model lacks chronicity and often leads to significant loss
      of mice. The aim of this study was to establish a refined and translationally
      relevant model of DSS chronic colitis in BALB/c mice. In the first part, we
      compared several standard therapeutic (ST) treatments for IBD in the acute DSS
      colitis model to identify the optimal treatment control for a DSS colitis model
      as compared to literature data. In the second part, we tested the two most
      effective ST treatments in a refined model of chronic DSS colitis. Cyclosporine A
      (CsA) and 6-thioguanine (6-TG) caused considerable reduction of clinical scores
      in acute DSS colitis. The clinical outcome was confirmed by the results for colon
      length and by histopathological evaluation. Moreover, CsA and 6-TG considerably
      reduced mRNA expression of several pro-inflammatory cytokines in spleen and
      colon. Both compounds also showed a substantial therapeutic effect in the refined
      model of chronic DSS colitis with regard to clinical scores and histopathology as
      well as the expression of inflammatory markers. The refined model of chronic DSS
      colitis reflects important features of IBD and is well suited to test potential
      IBD therapeutics.

PMID- 29192561
TI  - Genetic engineering as a powerful tool to improve probiotic strains.
AB  - Over the last decade, there has been increasing interest in the use of probiotic
      microorganisms. However, certain doubts have arisen around probiotics, because of
      the beneficial effects of these microorganisms are not clear yet, and in many
      occasions those beneficial effects have not been proven. Therefore, it would be
      of interest if these probiotic strains were able to acquire new attributes to
      allow them improve and increase their beneficial characteristics. Genetic
      engineering can be used for human applications; for instance, the resistance to
      antibiotics is removed and the probiotic bacteria are modified in its own DNA.
      This process can be achieved by: (1) the use of food-grade vectors derived from
      lactic acid bacteria and/or bifidobacteria cryptic plasmids, (2) the genes
      integration or deletion in the chromosome of the probiotic strain, by site
      specific recombination using the attP/integrase system, or by homologous
      recombination, using either suicide vectors, (3) using the clustered regularly
      interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (Cas)
      nuclease. Through genetic engineering, the knowledge of probiotic strains as well
      as its use could be improved, and the doubts about probiotics could be crumped.

PMID- 29192562
TI  - Cerebral microcirculatory alterations and the no-reflow phenomenon in vivo after
      experimental pediatric cardiac arrest.
AB  - Decreased cerebral blood flow (CBF) after cardiac arrest (CA) contributes to
      secondary ischemic injury in infants and children. We previously reported
      cortical hypoperfusion with tissue hypoxia early in a pediatric rat model of
      asphyxial CA. In order to identify specific alterations as potential therapeutic
      targets to improve cortical hypoperfusion post-CA, we characterize the CBF
      alterations at the cortical microvascular level in vivo using multiphoton
      microscopy. We hypothesize that microvascular constriction and disturbances of
      capillary red blood cell (RBC) flow contribute to cortical hypoperfusion post-CA.
      After resuscitation from 9 min asphyxial CA, transient dilation of capillaries
      and venules at 5 min was followed by pial arteriolar constriction at 30 and 60
      min (19.6 +/- 1.3, 19.3 +/- 1.2 um at 30, 60 min vs. 22.0 +/- 1.2 um at baseline,
      p < 0.05). At the capillary level, microcirculatory disturbances were highly
      heterogeneous, with RBC stasis observed in 25.4% of capillaries at 30 min post
      CA. Overall, the capillary plasma mean transit time was increased post-CA by
      139.7 +/- 51.5%, p < 0.05. In conclusion, pial arteriolar constriction, the no
      reflow phenomenon and increased plasma transit time were observed post-CA. Our
      results detail the microvascular disturbances in a pediatric asphyxial CA model
      and provide a powerful platform for assessing specific vascular-targeted
      therapies.

PMID- 29192563
TI  - Use of a Microcatheter to Cannulate the Contralateral Gate in Endovascular Aortic
      Repair.
AB  - Cannulation of the contralateral gate is a crucial step in endovascular aortic
      aneurysm repair (EVAR) to configure a modular stent-graft. Most commonly, the
      contralateral gate is cannulated retrogradely using a conventional catheter and
      hydrophilic guide wire; if this maneuver fails, a cross-over technique or
      additional access in the left brachial artery in association with a contralateral
      femoral snare catheter may be used. A cross-over technique using a microcatheter
      and a contralateral snare catheter might be a valuable alternative to cannulate
      the contralateral gate, especially in cases where there is a partly nondeployed
      contralateral stent-graft limb.

PMID- 29192564
TI  - Rare case of atypical parkinsonism: why family history is important.
AB  - We discuss the clinical presentation and assessment of a middle aged previously
      fit and well man who presented with two episodes of syncope to the cardiologists
      followed by the development of a rapidly progressive parkinsonian syndrome a
      couple of years later, which was not responsive to standard dopaminergic
      replacement therapies. Magnetic resonance imaging scan of the brain was normal
      and a DAT SPECT scan showed reduced dopamine uptake in the basal ganglia. On
      further enquiry, a family history of a similar presentation in his first cousin
      was elicited and that cousin had tested positive for a mutation in the PRNP gene.
      Subsequently, he also tested positive for A117V mutation in the PRNP gene,
      confirming familial Creutzfeld Jakob disease. Familial Creutzfeld Jakob disease
      presenting with parkinsonism is rare in clinical practice, but it is something
      that neurologists and geriatricians running movement disorder clinics should be
      aware of, as this is a rapidly progressive and uniformly fatal condition with
      inheritance risks to family members.

PMID- 29192565
TI  - [Meaningful treatments in orthopaedics and traumatology].
AB  - Reading the literature of recent years could give one the impression that many
      treatments fall short when they are submitted to high-quality scrutiny. This
      perspective discusses sensible and senseless care in orthopaedics and
      traumatology, using concepts such as evidence-based medicine, managing
      expectations and shared decision-making.

PMID- 29192566
TI  - [Breastfeeding in a multi-ethnic population: changes between 2009 and 2015].
AB  - OBJECTIVE: To examine changes in breastfeeding rates in 0 to 6 month old infants
      in Amsterdam, the Netherlands, over the period from 2009 to 2015, for the total
      population as well as for various ethnic groups. DESIGN: Cross-sectional study.
      METHOD: Breastfeeding rates were examined for the period from 2009 to 2015 in
      165,420 registrations of 75,543 infants at the ages of 2 weeks, 3 months and 6
      months for the entire Amsterdam population and for various ethnic groups.
      Differences were analysed using chi2 tests. RESULTS: The weighted percentage of
      total breastfeeding (exclusive breastfeeding as well as a combination of breast
      and formula feeding) increased in the entire Amsterdam study population over the
      period from 2009 to 2015 (2 weeks: 87.8% to 89.1%; 3 months: 61.6% to 63.6%; 6
      months: 39.5% to 42.2%). Increases were mainly the result of increases in
      weighted percentages for exclusive breastfeeding. The highest exclusive
      breastfeeding rates were observed among the Turkish ethnic group, the lowest
      among the Antillean/Aruban and Surinamese groups. CONCLUSION: Percentages for
      total breastfeeding as well as exclusive breastfeeding in Amsterdam rose over the
      period from 2009 to 2015, but there is room for improvement. Breastfeeding
      promotion, whether or not in combination with formula feeding, may be of
      particular benefit to children of Surinam or Antillean/Aruban descent. Before
      ethnicity-specific interventions can be implemented, more insight is needed in
      the reasons for the low breastfeeding rates in specific groups.

PMID- 29192567
TI  - [Assessment of physicians with a foreign diploma; results of 10 years of testing
      of physicians with a foreign diploma].
AB  - OBJECTIVE: To determine the result of the assessment procedure, initiated on 1
      December 2005, for physicians with a foreign diploma who wish to practice in the
      Netherlands. DESIGN: Retrospective, descriptive study. METHOD: The Commission for
      Foreign Healthcare Graduates (CBGV) collected data on physicians with a foreign
      diploma who followed the procedure for requesting a declaration of professional
      competence and admission to the Dutch Individual Healthcare Professions (BIG)
      register between December 2005 - December 2015. The procedure comprises a
      language and communication test, followed by tests of professional competence. On
      the grounds of the test results, the CBGV can decide if a physician should follow
      a specific training course. The number of physicians who ultimately obtained BIG
      registration was determined. RESULTS: During the study period, 183 of the 206
      physicians with a foreign diploma passed the general knowledge and skills tests.
      A total of 176 of the 183 physicians took the professional competence tests. In
      43 (25%) of them no shortcomings in knowledge and skills were seen. They were
      registered in the BIG register for a period of supervision. In 129 (73%),
      shortfalls were made up by means of focused training programme. In 4 (2%) of them
      no training was possible. On the date of assessment, 137 (78%) physicians were
      registered. This number is expected to rise to 151 (86%). CONCLUSION: The
      provision of a further course of training that is focused on the elimination of
      identified shortcomings in physicians with a foreign diploma, increases the
      percentage of foreign physicians that are successfully admitted to the BIG
      register.

PMID- 29192568
TI  - [Polymyalgia rheumatica: new developments and challenges].
AB  - - Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder in which
      inflammation markers, both erythrocyte sedimentation rate (ESR) and CRP values,
      are often elevated. However, a non-abnormal ESR or CRP value does not preclude
      the diagnosis.- PMR is an arbitrary diagnosis and presents both diagnostic and
      therapeutic challenges.- Imaging diagnostics, such as echography, MRI or FDG
      PET/CT, may potentially be applied more frequently as a second-line investigation
      when there is doubt concerning the diagnosis. Currently these additional imaging
      techniques are not applied in first line diagnostics.- Glucocorticoids remain the
      cornerstone treatment for polymyalgia rheumatica. Often patients react swiftly to
      this, but in 29-45% of cases an effect is only observed 3-4 weeks later. The
      treatment course typically lasts 1-3 years.- More research has been conducted
      into potential glucocorticoid-sparing treatments. Most of the scientific evidence
      concerns the effectiveness of methotrexate; there is some evidence regarding the
      effectiveness of azathioprine and leflunomide. Tocilizumab, an IL-6 receptor
      inhibitor, has shown promise as a treatment, but further evidence is required.

PMID- 29192569
TI  - [From record keeping to scientific research: obstacles and opportunities for
      research with electronic health records].
AB  - As a result of increasing digitisation of medical record keeping, electronic
      health records (EHRs) are an attractive source for data reuse. However, such
      record-based research is still suffering from poor quality of data stored in
      EHRs. Lack of consent for reuse of data also plays an impeding role, especially
      in retrospective record-based research. That said, increasing cooperation between
      healthcare institutions and current attention for EHR organisation also offer
      opportunities for record-based research. Patient data can be recorded in more
      standardised ways and in increasingly harmonised EHRs. In addition, if healthcare
      institutions were to establish a generic consent procedure - preferably with
      national scope - the potential of EHRs for scientific research could be exploited
      in considerably better ways.

PMID- 29192570
TI  - [Patients and physicians creating a research agenda together: the method of the
      British James Lind Alliance].
AB  - The British James Lind Alliance (JLA) has developed a method to allow
      practitioners, patients and family members together to develop a research agenda
      for a disease or a form of treatment. In a 'priority setting partnership', they
      gradually establish a top-10 list of the most important unanswered research
      questions. Input from patients and their relatives is given the same weight when
      determining priorities as that from practitioners. More than 50 of these top-10
      lists have been created so far, one of which was created in the Netherlands. The
      JLA method combines elements of the two very different methods currently
      prevailing in the Netherlands: the dialog model, developed by the VU and the
      'health care evaluation agenda', developed by the Dutch Association of Medical
      Specialists. The JLA method is quite practicable and leads to new research
      questions. The biggest advantage is that it leads to a dialogue between creators
      and users of knowledge about what the relevant research questions are.

PMID- 29192571
TI  - [A man with dyspnoea after a kidney transplant].
AB  - We present a 62-year-old man with a kidney transplant in the past. Because of
      progressive dyspnoea a CT-scan was made, which showed ground glass in the upper
      fields with calcifications. He was diagnosed with metastatic pulmonary
      calcification, which is mostly seen in patient with renal failure and secondary
      hyperparathyroidism.

PMID- 29192572
TI  - [Recognising postoperative delirium in the elderly].
AB  - OBJECTIVE: To determine the degree of agreement between delirium experts on the
      diagnosis of delirium based on exactly the same information, and to assess the
      sensitivity of delirium screening methods used by clinical nurses. DESIGN:
      Prospective observational longitudinal study. METHOD: Older patients (>= 60
      years) who underwent major surgery were included. During the first three days
      after surgery they had a standardised cognitive screening test which was recorded
      on video. Two delirium experts independently evaluated these videos and the
      information from the patient records. They classified the patients as having 'no
      delirium', 'possible delirium' or 'delirium'. If there was disagreement, a third
      expert was consulted. The final classification, based on consensus of two or
      three delirium experts, was compared with the result of the delirium screening
      carried out by the clinical nurses. RESULTS: A total of 167 patients were
      included and 424 postoperative classifications were obtained. The agreement
      between the experts was 0.61 (95% confidence interval (CI): 0.53-0.68), based on
      Cohen's kappa. In 89 (21.0%) of the postoperative classifications there was no
      agreement between the experts and a third expert was consulted. The nurses using
      the delirium screening tools recognised 32% of the cases that had been classified
      as delirium by the experts. CONCLUSION: There was considerable disagreement
      between the classifications of individual delirium experts, based on exactly the
      same information, indicating the difficulty of the diagnosis. Furthermore, the
      sensitivity of the delirium screening tools used by the clinical nurses was poor.
      Further research should focus on the development of objective methods for
      recognising delirium.

PMID- 29192573
TI  - [A female with expiratory wheezing and inspiratory stridor].
AB  - A 42-year-old woman was seen with an inspiratory stridor and expiratory wheezing.
      The wheezing responded quickly to asthma treatment. The stridor, however, was
      caused by a significant narrowing of the trachea between the branching of a
      tracheal bronchus ('bronchus suis' or ' pig bronchus') and the main carina.

PMID- 29192574
TI  - [A woman with skin rash and dyspnoea].
AB  - We present a 36-year-old woman who was born and raised in Hongkong but currently
      lived in the Netherlands. She was admitted with a varicella-zoster virus (VZV)
      primo-infection complicated by pneumonia and hepatitis. The patient was
      successfully treated with aciclovir. Adult VZV primo-infections are uncommon in
      Dutch natives but occur more often in immigrants from countries with a temperate
      climate where less people are infected during childhood.

PMID- 29192575
TI  - [Current dilemmas on the transmission of hepatitis E virus].
AB  - Immunocompromised patients are especially at risk for developing chronic
      hepatitis E virus (HEV) infection, which may result in progressive liver disease
      and cirrhosis. In addition, treatment of chronic HEV infection in these patients
      often includes dose reduction of immunosuppressive therapy and this may lead to
      severe flare-ups of the underlying condition or even rejection of transplant
      material. Therefore prevention of HEV transmission is being more and more
      recognised as an essential step to stop increasing HEV seroprevalence. The Dutch
      National Institute for Public Health and the Environment (RIVM) has recently
      warned immunocompromised patients following haematopoietic stem cell and solid
      organ transplantations for the risk of infection by HEV through eating of
      contaminated products from pig meat. Furthermore, the Dutch blood bank recently
      decided to start screening all blood products for HEV to prevent iatrogenic
      transmission of HEV. We describe two patients with HEV infection and discuss risk
      of infection for immunocompromised patients, transmission routes and the
      importance of prevention of iatrogenic transfusion related transmission.

PMID- 29192576
TI  - [Mothers in the Netherlands do not have to feel guilty about bottle-feeding their
      babies].
AB  - Human milk provides optimal nutrition for the term new-born infant. This milk
      might give the infant certain advantages over formula milk, and the potential
      advantages are reviewed in this commentary. It is concluded that there are
      advantages to breastfeeding, but that these are limited for an infant in an
      industrialised country receiving adequate formula milk. Breastfeeding should be
      encouraged, but there is insufficient reason for a mother who either is not able
      or not willing to breastfeed to feel guilty about not doing so.

PMID- 29192577
TI  - [Lower back pain: understanding it is more important than treating it].
AB  - Nonspecific lower back pain is frequently encountered in primary care, with 25
      50% of cases following a chronic course. Over recent decades, a large body of
      research has focused on the effectiveness of both pharmacological and non
      pharmacological treatments. However, hardly any effective interventions have been
      identified and the overall strength of evidence is low. We argue that the reason
      for these disappointing results lies in the 'nonspecific' nature of back pain. It
      is widely recognised that the causes for nonspecific back pain are not only
      biologically, but also psychologically and socially determined. Future research
      should emphasise aetiology and prognosis in order to enhance the development of
      tailored interventions.

PMID- 29192578
TI  - [Nitrous oxide-induced polyneuropathy].
AB  - Nitrous oxide, laughing gas, is used as a party drug to achieve a euphoric
      effect. It has been gaining popularity in recent years and is considered a
      relatively innocent substance. Nitrous oxide is known to cause subacute
      degeneration of the spinal cord by inactivation of active vitamin B12. Vitamin
      B12 plays an essential role in the synthesis of myelin. Hence, vitamin B12
      deficiency can lead to degeneration of the dorsal and lateral columns of the
      spinal cord. Polyneuropathy is a less known complication. We present a 17-year
      old woman and a 19-year-old man with subacute axonal polyneuropathy caused by
      laughing gas abuse. Abstinence of laughing gas and treatment with intramuscular
      and oral vitamin B12 suppletion respectively have led to improvement of their
      symptoms. Our cases demonstrate a less-known but treatable complication of
      laughing gas.

PMID- 29192579
TI  - [Heterogeneity of delirium cannot be captured by a simple diagnostic instrument].
AB  - The latest criteria for delirium (DSM-5) still encompass a very heterogeneous
      group of patients, as both risk factors and causes differ greatly between
      patients. This makes it unlikely that a single biomarker (e.g. an EEG signal) can
      be a valid and reliable diagnostic tool in clinical practice. Researchers should
      be very aware of this heterogeneity, as striving for uniform biomarkers would
      otherwise result in a considerable waste of research effort. In clinical
      practice, the delineation of delirium syndrome from dementia and coma using these
      DSM-5 criteria remains challenging. We state that patient outcomes can probably
      be improved most by interprofessional, personalised management and the monitoring
      of vulnerable patients during their individual disease trajectories.

PMID- 29192580
TI  - Copy Number Variants and Exome Sequencing Analysis in Six Pairs of Chinese
      Monozygotic Twins Discordant for Congenital Heart Disease.
AB  - Congenital heart disease (CHD) is one of the most common birth defects. More than
      200 susceptibility loci have been identified for CHDs, yet a large part of the
      genetic risk factors remain unexplained. Monozygotic (MZ) twins are thought to be
      completely genetically identical; however, discordant phenotypes have been found
      in MZ twins. Recent studies have demonstrated genetic differences between MZ
      twins. We aimed to test whether copy number variants (CNVs) and/or genetic
      mutation differences play a role in the etiology of CHDs by using single
      nucleotide polymorphism (SNP) genotyping arrays and whole exome sequencing of
      twin pairs discordant for CHDs. Our goal was to identify mutations present only
      in the affected twins, which could identify novel candidates for CHD
      susceptibility loci. We present a comprehensive analysis for the CNVs and genetic
      mutation results of the selected individuals but detected no consistent
      differences within the twin pairs. Our study confirms that chromosomal structure
      or genetic mutation differences do not seem to play a role in the MZ twins
      discordant for CHD.

PMID- 29192583
TI  - Abstracts From the 16th International Congress on Twin Studies and the 4th World
      Congress on Twin Pregnancy, Madrid, Spain November 16-18, 2017.

PMID- 29192581
TI  - Genetic Influences on Evening Preference Overlap with Those for Bipolar Disorder
      in a Sample of Mexican Americans and American Indians.
AB  - Diurnal preference (e.g., being an owl or lark) has been associated with several
      psychiatric disorders including bipolar disorder (BP), major depressive disorder,
      and substance use disorders. Previous large-scale genome-wide association studies
      (GWAS) aimed at identifying genetic influences on diurnal preference have
      exclusively included subjects of European ancestry. This study examined the
      genetic architecture of diurnal preference in two minority samples: a young adult
      sample of Mexican Americans (MAs), and a family-based sample of American Indians
      (AIs). Typed or imputed variants from exome chip data from the MA sample and low
      pass whole-genome sequencing from the AI cohort were analyzed using a mixed
      linear model approach for association with being an owl, as defined by a usual
      bedtime after 23:00 hrs. Genetic risk score (GRS) profiling detected shared
      genetic risk between evening preference and related disorders. Four variants in
      KIAA1549 like (KIAA1549L), a gene previously associated with attempted suicide in
      bipolar patients, were suggestively associated with being an owl at p < 1.82E-05;
      post hoc analyses showed the top variant trending in both the MA and AI cohorts
      at p = 2.50E-05 and p = .030, respectively. Variants associated with BP at p <
      .03 from the Psychiatric Genomics Consortium nominally predicted being an owl in
      the MA/AI cohort at p = .012. This study provides some additional evidence that
      genetic risk factors for BP also confer risk for being an owl in MAs/AIs and that
      evening preference may be a useful endophenotype for future studies of BP.

PMID- 29192586
TI  - Asymptomatic recurrence after AF ablation: Is all lost?

PMID- 29192588
TI  - Femoral venous hemostasis after atrial fibrillation ablation: Is figure-of-eight
      suture the way to go?

PMID- 29192587
TI  - The proportion of asymptomatic recurrence after catheter ablation of atrial
      fibrillation in patients with a pacemaker for sick sinus syndrome.
AB  - BACKGROUND: Catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) is an
      effective treatment. However, the frequency of asymptomatic AF recurrence after
      CA in patients with PAF and sick sinus syndrome (SSS) is not clear. The aim of
      this study was to elucidate the real AF recurrence after CA in patients with PAF
      and a pacemaker for SSS. METHODS AND RESULTS: Fifty-one consecutive patients
      (mean age 66.6 +/- 7.0 years, male 34) with PAF and SSS and pacemakers underwent
      CA. All patients were followed at 1, 3, 6, 9, and 12 months after the CA using a
      12-lead ECG, Holter-ECG, and 1-month event recorder as a conventional follow-up.
      In addition, the pacemakers were interrogated every 12 months. During a 5-year
      follow-up after the final CA procedure, AF recurrences were observed in 7
      patients (13.7%) with a conventional follow-up, including 1 (2.0%) asymptomatic
      patient. Pacemaker-interrogation revealed another 10 patients (19.6%) with
      asymptomatic AF recurrences. Ultimately, the conventional follow-up plus
      pacemaker-interrogation provided a higher incidence of AF recurrences (P =
      0.009). Multiple CA procedures contributed to a significant increase in the AF
      free survival rate at 5 years: 58.6% after a single CA and 86.0% after multiple
      CA procedures with a conventional follow-up, but which decreased to 40.6% and
      60.9% with a conventional follow-up plus a pacemaker interrogation, respectively.
      CONCLUSIONS: One-third of PAF patients with SSS and pacemakers recurred after
      multiple CA sessions. However, 65% of them were asymptomatic and difficult to be
      identified with conventional follow-up. Pacemaker interrogation significantly
      increased the detection rate of AF-recurrence.

PMID- 29192585
TI  - Yeast eIF4A enhances recruitment of mRNAs regardless of their structural
      complexity.
AB  - eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary
      structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their
      recruitment to the eukaryotic translation pre-initiation complex (PIC). We show
      that eIF4A's ATPase activity is markedly stimulated in the presence of the PIC,
      independently of eIF4E*eIF4G, but dependent on subunits i and g of the
      heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment
      of all mRNAs tested, regardless of their degree of structural complexity.
      Structures in the 5'-UTR and 3' of the start codon synergistically inhibit mRNA
      recruitment in a manner relieved by eIF4A, indicating that the factor does not
      act solely to melt hairpins in 5'-UTRs. Our findings that eIF4A functionally
      interacts with the PIC and plays important roles beyond unwinding 5'-UTR
      structure is consistent with a recent proposal that eIF4A modulates the
      conformation of the 40S ribosomal subunit to promote mRNA recruitment.

PMID- 29192589
TI  - Figure-of-eight suture for venous hemostasis in fully anticoagulated patients
      after atrial fibrillation catheter ablation.
AB  - INTRODUCTION: Limited data exists for types of venous closure and its associated
      complications in patients after atrial fibrillation (AF) catheter ablation. We
      evaluated the subcutaneous figure-of-eight closure (FO8) for achieving venous
      hemostasis after AF catheter ablation compared to manual pressure. METHODS: 284
      consecutive patients that underwent AF catheter ablation by two operators were
      included. All patients received continuous therapeutic warfarin or interrupted
      novel oral anticoagulants (NOAC) and heparin (ACT300-400 s) without reversal.
      Patients were divided into two groups: 1) sheaths were left in place and pulled
      once ACT < 180 s, with hemostasis being achieved with manual pressure (MP); and
      2) a subcutaneous FO8 suture closed the venous access site immediately after the
      ablation on each groin site and sheaths were removed immediately after the
      ablation despite full anticoagulation with heparin and warfarin or interrupted
      NOAC. Sutures were removed after four hours, and the patients laid flat for an
      additional two hours. RESULTS: The MP group (n = 105) was similar to the FO8
      group (n = 179). Time in bed was 573 +/- 80 min for MP group vs. 373 +/- 49 min
      for FO8 group (p < 0.0001). Eleven hematomas were seen in the MP group compared
      to seven in the FO8 group (P = 0.041). CONCLUSIONS: In fully anticoagulated
      patients undergoing AF catheter ablation, excellent hemostasis was achieved with
      figure-of-eight sutures, with no major vascular complications, a lower hematoma
      rate, and a significantly shorter flat-time-in-bed compared to manual pressure.

PMID- 29192590
TI  - Catheter ablation in the treatment of electrical storm: Integrative review.
AB  - BACKGROUND: The incidence of electrical storm (ES) has been increasing with the
      rise of the indicated uses of implantable cardioverter defibrillators (ICDs). It
      is estimated that 20% of patients will evolve to have this complication. Ablative
      therapy stands out as the treatment for this condition when it is refractory to
      antiarrhythmic treatment. The objective was to define the current role of
      catheter ablation in the treatment of electrical storm. METHODS: An integrative
      literature review was performed using the PubMed and BVS databases. All
      identified articles were screened and verified for eligibility by the authors.
      RESULTS: Twenty-five out of the initial 951 articles were used in the final
      analysis. The categories listed for analysis included indication for ablation in
      ES, modality of the approach, therapeutic success, complications related to the
      procedure, mortality and cardiovascular follow-up and alternative therapeutic
      modalities by frequency of these categories in the articles researched.
      CONCLUSION: Catheter ablation is the initial therapy for patients with ischemic
      cardiomyopathy (ICM) and ES. The endocardial approach presents more relevant
      success rates than the other therapeutic methods presented.

PMID- 29192591
TI  - Torsades de Pointes associated with QT prolongation after catheter ablation of
      paroxysmal atrial fibrillation.
AB  - A 79-year-old woman who underwent catheter ablation for paroxysmal atrial
      fibrillation presented with Torsades de Pointes (TdP). Aggravation of prolonged
      QT interval which is most likely due to neural modulation by catheter ablation,
      played major role in the initiation of TdP. The patient was successfully treated
      with isoproterenol during acute stage and discharged after stabilization without
      implantation of permanent pacemaker or implantable cardioverter defibrillator.

PMID- 29192592
TI  - A case of an atrial tachycardia originating from an occluded coronary sinus
      ostium with a persistent left superior vena cava.
AB  - We present a case of a 37-year-old female who complained of frequent palpitations
      caused by an atrial tachycardia and atrial premature contractions. Angiography
      revealed that the coronary sinus was occluded at the ostium and connected to a
      persistent left superior vena cava. An electrophysiological study and three
      dimensional mapping revealed that the origin of the atrial tachycardia and atrial
      premature contractions was at the coronary sinus ostium in the right atrium.
      After repeat applications of radiofrequency energy at that site, no further
      atrial tachycardia or atrial premature contractions were induced by atrial burst
      pacing. To the best of our knowledge, this is the first report of an atrial
      tachycardia originating from an occluded coronary sinus ostium.

PMID- 29192593
TI  - Total epicardial biventricular pacing and defibrillation- A case report.

PMID- 29192594
TI  - Multi-site multi-polar left ventricular pacing through persistent left superior
      vena cava in tricuspid valve disease.
AB  - Multi-site multi-polar left ventricular pacing through the coronary sinus (CS)
      may be preferred over endocardial right ventricular or surgical epicardial pacing
      in the presence of tricuspid valve disease. However, the required lead placement
      can be difficult through a persistent left superior vena cava (PLSVC), as the CS
      tends to be hugely dilated and side branches tend to have sharp angulations (>90
      degrees ) when approached from the PLSVC. Pre-shaped angiography catheters and
      techniques used for finding venous grafts from the ascending aorta post coronary
      bypass surgery may help with lead placement in such a situation.

PMID- 29192595
TI  - Multiple pacemaker lead breakages due to clavicle dislocation following clavicle
      fracture.
AB  - A 58-year-old man undergoing cardiac resynchronization therapy with a
      defibrillator in his right subcostal area fell from his bed, leading to fracture
      of the right clavicle. Serial radiographs showed dislocation of the distal
      clavicle 2 months after the initial fracture. Lead parameters dramatically
      changed after dislocation of the distal clavicle. Radiography indicated that the
      device leads seemed to be compressed by the distal clavicle in certain positions
      of the right upper limb. It was likely that various movements of the right upper
      limb during his daily life insidiously damaged the device leads, leading to the
      lead breakages.

PMID- 29192596
TI  - Detection of RAS mutations in circulating tumor cells: applications in colorectal
      cancer and prospects.
AB  - The somatic mutations in the RAS genes (KRAS and NRAS) are widely associated with
      non-response to immunotherapies targeting the epidermal growth factor receptor in
      metastatic colorectal cancer. The detection of these mutations is carried out
      from tissue biopsies and become mandatory to prescribe these treatments.
      Nethertheless, this analysis is not possible in about 25% of cases and the
      development of alternative methods is therefore required. Among them, the search
      for mutations directly in the blood of patients are promising approaches.
      Circulating tumor cells (CTCs) represent a particularly relevant direct target.
      These cells, some of them have inducing-metastasis capabilities, have been able
      to detach themselves from the primary tumor, then migrate and finally enter into
      the bloodstream. In this sense, they are particularly resistant to physical
      chemical and immunological constraints used by the organism to prevent their
      dissemination. Consequently, they represent a particularly valuable source of
      information on the most aggressive tumor cells. As a corollary, these cells are
      very rare requiring particularly highly performant technologies to be detected.
      In this presentation, we focus mainly on the molecular methods used to detect
      these mutated RAS cells by analyzing the performance of a solution based on a
      filtration device followed by detection with digital PCR. Finally, we will
      discuss the biological significance of these cells before highlighting prospects
      in colorectal cancer but also in other cancers.

PMID- 29192597
TI  - Circulating tumour DNA: analytical aspects and clinical applications for
      metastatic melanoma patients.
AB  - The management of metastatic melanoma has evolved since the onset of treatments
      with BRAF inhibitors. In order to predict which patients are likely to respond to
      these treatments, the therapeutic strategy is now conditioned by the search for
      the activating mutations of the BRAF gene. Tumor genotyping is routinely
      performed from DNA extracted from tissue or cellular specimens from the primary
      tumor, metastases, or neoplastic effusions. Due to their invasiveness, these
      specimens are rarely repeated during the management. In addition, the analysis of
      the tumor material requires a pretreatment of the sample (formalin fixation,
      paraffin inclusion, preparation of tissue sections) and may take up to several
      weeks, making emergency treatment with BRAF inhibitors impossible. Circulating
      tumor DNA (ctDNA), released by cancer cells in the blood stream, appears as an
      alternative to tissue sampling. The pre-analytical conditions are now well
      defined, and several technological approaches can be used to demonstrate the
      desired molecular alterations. ctDNA is less affected by tumor heterogeneity, can
      be collected in a minimally invasive manner and analyzed rapidly. Furthermore,
      ctDNA can be repeatedly analyzed during follow-up, which makes it possible to
      envisage its use as a specific tumor marker, in order to monitor the response to
      the treatment and to detect treatment failure.

PMID- 29192598
TI  - Personalized medicine, pharmacogenomic and companion biomarker.
AB  - The aim of this review is to provide a brief overview of personalized medicine,
      pharmacogenetics and companion tests. Personalized or stratified medicine is a
      new paradigm in the management of patients, aimed at better taking into account
      inter-individual variability. The response to drugs' intake varies considerably,
      depending on the transport and metabolism of the drugs, the target and the
      pathophysiological characteristics of the organism. Each stage is very variable
      and can be modified by endogenous factors (pathophysiology, age, sex,
      genetics...) or exogenous (environmental: taking other medicines, food, tobacco,
      alcohol...). Pharmacogenetics studies the genetic factors involved in the
      pharmacological or toxicological response to drugs. Companion tests that are
      often based on a pharmacogenetic principle aim to identify in a patient's
      population those who will respond to a given treatment.

PMID- 29192599
TI  - Medical laboratory technician professional pathologies: a 2006-2016 literature
      review.
AB  - The trade of laboratory technician (TL) exposes to many risks to health, because
      of biological or chemical or physical exposures. But the TL occupation is
      constantly evolving, the techniques are constantly changing. The purpose of this
      article is to take stock of the occupational TL pathologies which were recently
      described in the literature. This is a literature review, based on Medline(r) and
      Scopus(r) medical databases, on publications between 01/01/2006 and 31/12/2016.
      The research was conducted in French and English. Only articles about TL in
      Hospital or Teaching Hospital were selected. Twenty-eight articles were studied.
      The main infectious pathology described was brucellosis and a case of meningitis
      was studied. The cutaneous allergies reported concerned sensitization to certain
      solvents. There was no allergy to latex. Musculoskeletal disorders (MSD) were
      studied in 4 articles. The main MSDs were low back pain and neck pain. Several
      articles have alerted on the occurrence of burnout syndrome (BO). However, no
      prevalence studies were conducted over the period studied. In conclusion, TL can
      present many occupational pathologies. Few articles studied the prevalence of MSD
      and BO.

PMID- 29192600
TI  - Magazines in waiting areas of hospital: a forgotten microbial reservoir?
AB  - The hospital environment is a potential source of microbial contamination. Thus,
      the magazines in hospital's waiting rooms are handled by patients and visitors
      whose health and hygiene conditions can vary widely. In this context, we had
      measured the microbial load on the surface of magazines. Fifteen magazines from 5
      waiting rooms of hospital are sampled by agar prints at the areas taken in hand.
      The agar plates are incubated at 30C for 72h. The colonies are counted and
      identified by MALDI-TOF mass spectrometry (Vitek(r)-MS). The extraction
      efficiency of bacteria by the agar print method on the magazines is calculated.
      All the samples highlight a varied bacterial flora: 32CFU/agar in mean. Isolated
      bacteria come principally from the skin flora (>60%), but we also isolate
      potentially pathogenic micro-organisme like S. aureus, E. faecalis, A. viridans
      and Aspergillus sp. as well as oropharyngeal flora bacteria like A. iwolfii and
      M. osloensis and fecal like B. stercoris. Some species rarely described in
      hospital are also isolated such as P. yeei or K. sedentarius. The extraction
      efficiency of the sampling method on a magazine is 36%. Our study, which is the
      first to be interested in the bacterial contamination of magazines in hospital,
      could make them consider as microbial reservoir to be controlled, especially for
      the most fragile patients. New bacterial identification techniques as the MALDI
      TOF allow to reveal the presence of rarely described and often underestimated
      species.

PMID- 29192603
TI  - Cyclic Guanosine Monophosphate-Dependent Protein Kinase I Stimulators and
      Activators Are Therapeutic Alternatives for Sickle Cell Disease.

PMID- 29192601
TI  - Infectious aneurysm of the two primary iliac arteries: rare localization of
      Salmonella typhimurium infection.
AB  - Infectious aneurysm is a severe entity of the aneurysmal pathology, due
      essentially to a bacterial agent. The most frequently implicated organisms are
      salmonella and staphylococci. We report the case of an infectious aneurysm of the
      two primitive iliac arteries with Salmonella typhimurium in a 70-year-old man.

PMID- 29192604
TI  - Leukoagglutination, Mycoplasma pneumoniae Pneumonia, and EDTA Acid Blood.

PMID- 29192605
TI  - Interval-based reconstruction for uncertainty quantification in PET.
AB  - A new directed interval-based tomographic reconstruction algorithm, called non
      additive interval based expectation maximization (NIBEM) is presented. It uses
      non-additive modeling of the forward operator that provides intervals instead of
      single-valued projections. The detailed approach is an extension of the maximum
      likelihood-expectation maximization algorithm based on intervals. The main
      motivation for this extension is that the resulting intervals have appealing
      properties for estimating the statistical uncertainty associated with the
      reconstructed activity values. After reviewing previously published theoretical
      concepts related to interval-based projectors, this paper describes the NIBEM
      algorithm and gives examples that highlight the properties and advantages of this
      interval valued reconstruction.

PMID- 29192606
TI  - Reply to Comment on 'egs_brachy: a versatile and fast Monte Carlo code for
      brachytherapy'.
AB  - We respond to the comments by Dr Yegin by identifying the source of an error in a
      fit in our original paper but arguing that the lack of a fit does not affect the
      conclusion based on the raw data that [Formula: see text] is an accurate code and
      we provide further benchmarking data to demonstrate this point.

PMID- 29192607
TI  - Modelling the impact of altered axonal morphometry on the response of
      regenerative nervous tissue to electrical stimulation through macro-sieve
      electrodes.
AB  - OBJECTIVE: Regenerated peripheral nervous tissue possesses different morphometric
      properties compared to undisrupted nerve. It is poorly understood how these
      morphometric differences alter the response of the regenerated nerve to
      electrical stimulation. In this work, we use computational modeling to explore
      the electrophysiological response of regenerated and undisrupted nerve axons to
      electrical stimulation delivered by macro-sieve electrodes (MSEs). APPROACH: A 3D
      finite element model of a peripheral nerve segment populated with mammalian
      myelinated axons and implanted with a macro-sieve electrode has been developed.
      Fiber diameters and morphometric characteristics representative of undisrupted or
      regenerated peripheral nervous tissue were assigned to core conductor models to
      simulate the two tissue types. Simulations were carried out to quantify
      differences in thresholds and chronaxie between undisrupted and regenerated fiber
      populations. The model was also used to determine the influence of axonal caliber
      on recruitment thresholds for the two tissue types. Model accuracy was assessed
      through comparisons with in vivo recruitment data from chronically implanted
      MSEs. MAIN RESULTS: Recruitment thresholds of individual regenerated fibers with
      diameters  >2 um were found to be lower compared to same caliber undisrupted
      fibers at electrode to fiber distances of less than about 90-140 um but roughly
      equal or higher for larger distances. Caliber redistributions observed in
      regenerated nerve resulted in an overall increase in average recruitment
      thresholds and chronaxie during whole nerve stimulation. Modeling results also
      suggest that large diameter undisrupted fibers located close to a longitudinally
      restricted current source such as the MSE have higher average recruitment
      thresholds compared to small diameter fibers. In contrast, large diameter
      regenerated nerve fibers located in close proximity of MSE sites have, on
      average, lower recruitment thresholds compared to small fibers. Utilizing
      regenerated fiber morphometry and caliber distributions resulted in accurate
      predictions of in vivo recruitment data. SIGNIFICANCE: Our work uses
      computational modeling to show how morphometric differences between regenerated
      and undisrupted tissue results in recruitment threshold discrepancies, quantifies
      these differences, and illustrates how large undisrupted nerve fibers close to
      longitudinally restricted current sources have higher recruitment thresholds
      compared to adjacently positioned smaller fibers while the opposite is true for
      large regenerated fibers.

PMID- 29192608
TI  - Focus on 2D materials beyond graphene.

PMID- 29192609
TI  - Superior arm-movement decoding from cortex with a new, unsupervised-learning
      algorithm.
AB  - OBJECTIVE: The aim of this work is to improve the state of the art for motor
      control with a brain-machine interface (BMI). BMIs use neurological recording
      devices and decoding algorithms to transform brain activity directly into real
      time control of a machine, archetypically a robotic arm or a cursor. The standard
      procedure treats neural activity-vectors of spike counts in small temporal
      windows-as noisy observations of the kinematic state (position, velocity,
      acceleration) of the fingertip. Inferring the state from the observations then
      takes the form of a dynamical filter, typically some variant on Kalman's (KF).
      The KF, however, although fairly robust in practice, is optimal only when the
      relationships between variables are linear and the noise is Gaussian, conditions
      usually violated in practice. APPROACH: To overcome these limitations we
      introduce a new filter, the 'recurrent exponential-family harmonium' (rEFH), that
      models the spike counts explicitly as Poisson-distributed, and allows for
      arbitrary nonlinear dynamics and observation models. Furthermore, the model
      underlying the filter is acquired through unsupervised learning, which allows
      temporal correlations in spike counts to be explained by latent dynamics that do
      not necessarily correspond to the kinematic state of the fingertip. MAIN RESULTS:
      We test the rEFH on offline reconstruction of the kinematics of reaches in the
      plane. The rEFH outperforms the standard, as well as three other state-of-the
      art, decoders, across three monkeys, two different tasks, most kinematic
      variables, and a range of bin widths, amounts of training data, and numbers of
      neurons. SIGNIFICANCE: Our algorithm establishes a new state of the art for
      offline decoding of reaches-in particular, for fingertip velocities, the variable
      used for control in most online decoders.

PMID- 29192610
TI  - Comment on 'egs_brachy: a versatile and fast Monte Carlo code for brachytherapy'.
AB  - In a recent paper (Chamberland et al 2016 Phys. Med. Biol. 61 8214) develop a new
      Monte Carlo code called egs_brachy for brachytherapy treatments. It is based on
      EGSnrc, and written in the C++ programming language. In order to benchmark the
      egs_brachy code, the authors use it in various test case scenarios in which
      complex geometry conditions exist. Another EGSnrc based brachytherapy dose
      calculation engine, BrachyDose, is used for dose comparisons. The authors fail to
      prove that egs_brachy can produce reasonable dose values for brachytherapy
      sources in a given medium. The dose comparisons in the paper are erroneous and
      misleading. egs_brachy should not be used in any further research studies unless
      and until all the potential bugs are fixed in the code.

PMID- 29192611
TI  - Quantifying the radiant exposure and effective dose in patients treated for
      actinic keratoses with topical photodynamic therapy using daylight and LED white
      light.
AB  - Daylight photodynamic therapy (dl-PDT) is as effective as conventional PDT (c
      PDT) for treating actinic keratoses but has the advantage of reducing patient
      discomfort significantly. Topical dl-PDT and white light-PDT (wl-PDT) differ from
      c-PDT by way of light sources and methodology. We measured the variables
      associated with light dose delivery to skin surface and influence of geometry
      using a radiometer, a spectral radiometer and an illuminance meter. The
      associated errors of the measurement methods were assessed. The spectral and
      spatial distribution of the radiant energy from the LED white light source was
      evaluated in order to define the maximum treatment area, setup and treatment
      protocol for wl-PDT. We compared the data with two red LED light sources we use
      for c-PDT. The calculated effective light dose is the product of the normalised
      absorption spectrum of the photosensitizer, protoporphyrin IX (PpIX), the
      irradiance spectrum and the treatment time. The effective light dose from
      daylight ranged from 3  +/-  0.4 to 44  +/-  6 J cm-2due to varying weather
      conditions. The effective light dose for wl-PDT was reproducible for treatments
      but it varied across the treatment area between 4  +/-  0.1 J cm-2 at the edge
      and 9  +/-  0.1 J cm-2 centrally. The effective light dose for the red waveband
      (615-645 nm) was 0.42  +/-  0.05 J cm-2 on a clear day, 0.05  +/-  0.01 J cm-2 on
      an overcast day and 0.9  +/-  0.01 J cm-2 using the white light. This compares
      with 0.95  +/-  0.01 and 0.84  +/-  0.01 J cm-2 for c-PDT devices. Estimated
      errors associated with indirect determination of daylight effective light dose
      were very significant, particularly for effective light doses less than 5 J cm-2
      (up to 83% for irradiance calculations). The primary source of error is in
      establishment of the relationship between irradiance or illuminance and effective
      dose. Use of the O'Mahoney model is recommended using a calibrated logging
      illuminance meter with the detector in the plane of the treatment area.

PMID- 29192613
TI  - A Health-Based Metric for Evaluating the Effectiveness of Noise Barrier
      Mitigation Associated With Transport Infrastructure Noise.
AB  - INTRODUCTION: This study examines the use of the number of night-time sleep
      disturbances as a health-based metric to assess the cost effectiveness of rail
      noise mitigation strategies for situations, wherein high-intensity noises
      dominate such as freight train pass-bys and wheel squeal. MATERIALS AND METHODS:
      Twenty residential properties adjacent to the existing and proposed rail tracks
      in a noise catchment area of the Epping to Thornleigh Third Track project were
      used as a case study. Awakening probabilities were calculated for individual's
      awakening 1, 3 and 5 times a night when subjected to 10 independent freight train
      pass-by noise events using internal maximum sound pressure levels (LAFmax).
      RESULTS: Awakenings were predicted using a random intercept multivariate logistic
      regression model. With source mitigation in place, the majority of the residents
      were still predicted to be awoken at least once per night (median 88.0%),
      although substantial reductions in the median probabilities of awakening three
      and five times per night from 50.9 to 29.4% and 9.2 to 2.7%, respectively, were
      predicted. This resulted in a cost-effective estimate of 7.6-8.8 less people
      being awoken at least three times per night per A$1 million spent on noise
      barriers. CONCLUSION: The study demonstrates that an easily understood metric can
      be readily used to assist making decisions related to noise mitigation for large
      scale transport projects.

PMID- 29192612
TI  - Aviation Noise Impacts: State of the Science.
AB  - Noise is defined as "unwanted sound." Aircraft noise is one, if not the most
      detrimental environmental effect of aviation. It can cause community annoyance,
      disrupt sleep, adversely affect academic performance of children, and could
      increase the risk for cardiovascular disease of people living in the vicinity of
      airports. In some airports, noise constrains air traffic growth. This consensus
      paper was prepared by the Impacts of Science Group of the Committee for Aviation
      Environmental Protection of the International Civil Aviation Organization and
      summarizes the state of the science of noise effects research in the areas of
      noise measurement and prediction, community annoyance, children's learning, sleep
      disturbance, and health. It also briefly discusses civilian supersonic aircraft
      as a future source of aviation noise.

PMID- 29192614
TI  - Using Smart Devices to Measure Intermittent Noise in the Workplace.
AB  - PURPOSE: To determine the accuracy of smart devices (iPods) to measure
      intermittent noise and integrate a noise dose in the workplace. MATERIALS AND
      METHODS: In experiment 1, four iPods were each paired with a Larson Davis Spark
      dosimeter and exposed to randomly fluctuating pink noise in a reverberant sound
      chamber. Descriptive statistics and the mean difference between the iPod and its
      paired dosimeter were calculated for the 1-s data logged measurements. The
      calculated time weighted average (TWA) was also compared between the devices. In
      experiment 2, 15 maintenance workers and 14 office workers wore an iPod and
      dosimeter during their work-shift for a maximum of five workdays. A mixed effects
      linear regression model was used to control for repeated measures and to
      determine the effect of the device type on the projected 8-h TWA. RESULTS: In
      experiment 1, a total of 315,306 1-s data logged measurements were made. The
      interquartile range of the mean difference fell within +/-2.0 A-weighted decibels
      (dBA), which is the standard used by the American National Standards Institute to
      classify a type 2 sound level meter. The mean difference of the calculated TWA
      was within +/-0.5 dBA except for one outlier. In experiment 2, the results of the
      mixed effects model found that, on average, iPods measured an 8-h TWA 1.7 dBA
      higher than their paired dosimeters. CONCLUSION: This study shows that iPods have
      the ability to make reasonably accurate noise measurements in the workplace, but
      they are not as accurate as traditional noise dosimeters.

PMID- 29192615
TI  - Effects of Soundscape on the Environmental Restoration in Urban Natural
      Environments.
AB  - CONTEXT: According to the attention restoration theory, directed attention is a
      limited physiological resource and is susceptible to fatigue by overuse. Natural
      environments are a healthy resource, which allows and promotes the restoration of
      individuals within it from their state of directed attention fatigue. This
      process is called the environmental restoration on individuals, and it is
      affected both positively and negatively by environmental factors. AIMS: By
      considering the relationship among the three components of soundscape, that is,
      people, sound and the environment, this study aims to explore the effects of
      soundscape on the environmental restoration in urban natural environments.
      MATERIALS AND METHODS: A field experiment was conducted with 70 participants
      (four groups) in an urban natural environment (Shenyang, China). Directed
      attention was first depleted with a 50-min 'consumption' phase, followed by a
      baseline measurement of attention level. Three groups then engaged in 40 min of
      restoration in the respective environments with similar visual surroundings but
      with different sounds present, after which attention levels were re-tested. The
      fourth group did not undergo restoration and was immediately re-tested. The
      difference between the two test scores, corrected for the practice effect,
      represents the attention restoration of individuals exposed to the respective
      environments. STATISTICAL ANALYSIS USED: An analysis of variance was performed,
      demonstrating that the differences between the mean values for each group were
      statistically significant [sig. = 0.027 (<0.050)]. RESULTS: The results showed
      that the mean values (confidence interval of 95%) of each group are as follows:
      'natural sounds group' (8.4), 'traffic sounds group' (2.4) and 'machine sounds
      group' (-1.8). CONCLUSION: It can be concluded that (1) urban natural
      environments, with natural sounds, have a positive effect on the restoration of
      an individuals' attention and (2) the presence of different types of sounds has
      significantly divergent effects on the environmental restoration.

PMID- 29192616
TI  - Assessment of Reduced Tolerance to Sound (Hyperacusis) in University Students.
AB  - INTRODUCTION: Hyperacusis is defined as a reduction in tolerance to ordinary
      environmental sounds. Hyperacusis can occur in individuals of all age groups,
      making daily life difficult for the sufferers. Although there is no objective
      test to accurately diagnose hyperacusis, questionnaires are useful for the
      assessment of hyperacusis. The aim of this study was to explore the reduced sound
      tolerance in university students using a hyperacusis questionnaire (HQ).
      MATERIALS AND METHODS: A total of 536 university students (300 females and 236
      males) aged between 18 and 25 years, with a mean age of 21.34 +/- 1.87 years,
      were assessed using an HQ developed by Khalfa. The mean total score of all the
      participants was 16.34 +/- 7.91, and 5.78% of the participants had total scores
      indicating hyperacusis, where a majority of them were females. RESULTS: Females
      had significantly higher scores than men in terms of both the total and the
      attentional and emotional dimensions. The scores of the participants who reported
      noise exposure or a decrease in their tolerance to noise were significantly
      higher than those of the other participants. Even among young adults, there was a
      group of participants suffering from some problems related to decreased tolerance
      to everyday sounds. DISCUSSION: Although the Turkish translation of the HQ seems
      to be a reliable tool for evaluating hyperacusis in young adults, further work
      with various populations of different age groups is required to establish
      validity and to assess the psychometric qualities of the Turkish form.

PMID- 29192617
TI  - The Effects of Low-Frequency Noise on Rats: Evidence of Chromosomal Aberrations
      in the Bone Marrow Cells and the Release of Low-Molecular-Weight DNA in the Blood
      Plasma.
AB  - OBJECTIVES: Evaluation of the effect of low-frequency noise (LFN) on the
      frequency of chromosomal aberrations in the bone marrow cells and on the content
      of low-molecular-weight DNA (lmwDNA) in the blood plasma of rats. MATERIALS AND
      METHODS: A total of 96 male Wistar rats were exposed to either single (17 min
      session) or multiple (17 min session repeated five times a week for 13 weeks)
      LFN, with the maximum range below 250 Hz and the sound pressure levels (SPLs) at
      120 and 150 dB, respectively. The rats in the control groups were not subjected
      to any impact. The frequency of chromosomal aberrations in the bone marrow cells
      and the levels of lmwDNA in the blood plasma were measured afterwards. RESULTS:
      It has been detected that a single LFN exposure with either corresponding SPLs
      had a significant increase in the frequency of chromosomal aberrations (more than
      10-fold) compared to the controls (0.9 +/- 0.3%) and resulted in the appearance
      of dicentric chromosomes in the aberration spectrum, both of which are evident
      for the occurrence of deoxyribonucleic acid double strand breaks triggered by the
      exposure. Furthermore, the lmwDNA levels in the blood plasma measured the
      following day after a single LFN exposure were significantly higher (7.7- and 7.6
      fold, respectively) than that in the control group (11.0 +/- 5.4 ng/ml), and such
      levels were maintained higher (4.8- and 2.1-fold, respectively) in the week after
      a single LFN exposure for the SPL of 120 and 150 dB, respectively, compared to
      the control group (18.8 +/- 1.6 ng/ml). Similar results were obtained from the
      group with multiple LFN exposures (36.4- and 22.4-fold, respectively) compared to
      the control (17.7 +/- 1.7 ng/ml) and suggest the enhancement of cellular
      apoptosis as a result of the LFN impact. CONCLUSION: Presumably, the LFN may have
      possible mutagenic effects and cause massive cell death.

PMID- 29192619
TI  - Tinnitus, Medial Olivocochlear System, and Music Exposure in Adolescents.
AB  - INTRODUCTION: The most common cause of tinnitus is the exposure to noise; in the
      case of adolescents, music is the main sound source they are exposed to.
      Currently, one of the hypotheses about the genesis of tinnitus is related to the
      deterioration in the functioning of the medial olivocochlear system (MOCS). AIM:
      The aim of this study was to determine the presence or absence of tinnitus in
      adolescents with normal hearing and to relate it to: (a) the functioning of the
      MOCS, by the contralateral suppression of the transient evoked otoacoustic
      emissions (TEOAEs) and (b) the musical general exposure (MGE). MATERIALS AND
      METHODS: A cross-sectional descriptive correlational study was conducted. The
      sample was composed by adolescents with ages between 14 and 15. Two
      questionnaires were administered, one in relation to the subjective report of
      tinnitus and the other in relation to recreational activities to know the MGE.
      RESULTS: The results showed that the amplitude of frequencies (1000, 1500, 2000,
      and 3000 Hz) and global amplitude of TEOAEs, with and without acoustic
      contralateral stimulation, were higher in the group without tinnitus, with a
      statistically significant difference (P < 0.05). The suppressive effect was
      higher in the group without tinnitus; however, there was no statistically
      significant difference. Contrastingly, a significant association (P < 0.05)
      between exposure to music and tinnitus was observed; 72.41% of the adolescents
      with high exposure to music had tinnitus. DISCUSSION AND CONCLUSION: The results
      of the present investigation provide a contribution to the hypothesis of "the
      participation of the MOCS." Furthermore, a high MGE can be considered a risk
      factor for the onset of tinnitus.

PMID- 29192618
TI  - How Children Perceive the Acoustic Environment of Their School.
AB  - OBJECTIVE: Children's own ratings and opinions on their schools sound
      environments add important information on noise sources. They can also provide
      information on how to further improve and optimize children's learning situation
      in their classrooms. This study reports on the Swedish translation and
      application of an evidence-based questionnaire that measures how children
      perceive the acoustic environment of their school. STUDY DESIGN: The Swedish
      version was made using a back-to-back translation. Responses on the questionnaire
      along with demographic data were collected for 149 children aged 9-13 years of
      age. RESULTS: The Swedish translation of the questionnaire can be reduced from 93
      to 27 items. The 27 items were distributed over five separate factors measuring
      different underlying constructs with high internal consistency and high inter
      item correlations. The responses demonstrated that the dining hall/canteen and
      the corridors are the school spaces with the poorest listening conditions. The
      highest annoyance was reported for tests and reading; next, student-generated
      sounds occur more frequently within the classroom than any sudden unexpected
      sounds, and finally, road traffic noise and teachers in adjoining classrooms are
      the most frequently occurring sounds from outside the classroom. Several
      demographic characteristics could be used to predict the outcome on these
      factors. CONCLUSION: The findings suggest that crowded spaces are most
      challenging; the children themselves generate most of the noise inside the
      classroom, but it is also common to hear road traffic noise and teachers in
      adjoining classrooms. The extent of annoyance that noise causes depends on the
      task but seems most detrimental in tasks, wherein the demands of verbal
      processing are higher. Finally, children with special support seem to report that
      they are more susceptible to noise than the typical child.

PMID- 29192620
TI  - Noise-Induced Hearing Loss - A Preventable Disease? Results of a 10-Year
      Longitudinal Study of Workers Exposed to Occupational Noise.
AB  - AIMS: To survey current, Danish industrial noise levels and the use of hearing
      protection devices (HPD) over a 10-year period and to characterise the
      association between occupational noise and hearing threshold shift in the same
      period. Furthermore, the risk of hearing loss among the baseline and the follow
      up populations according to first year of occupational noise exposure is
      evaluated. MATERIALS AND METHODS: In 2001-2003, we conducted a baseline survey of
      noise- and hearing-related disorders in 11 industries with suspected high noise
      levels. In 2009-2010, we were able to follow up on 271 out of the 554 baseline
      workers (49%). Mean noise levels per industry and self-reported HPD use are
      described at baseline and follow-up. The association between cumulative
      occupational noise exposure and hearing threshold shift over the 10-year period
      was assessed using linear regression, and the risk of hearing loss according to
      year of first occupational noise exposure was evaluated with logistic regression.
      RESULTS: Over the 10-year period, mean noise levels declined from 83.9 dB(A) to
      82.8 dB(A), and for workers exposed >85 dB(A), the use of HPD increased from 70.1
      to 76.1%. We found a weak, statistically insignificant, inverse association
      between higher ambient cumulative noise exposure and poorer hearing (-0.10 dB
      hearing threshold shift per dB-year (95% confidence interval (CI): -0.36; 0.16)).
      The risk of hearing loss seemed to increase with earlier first year of noise
      exposure, but odds ratios were only statistically significant among baseline
      participants with first exposure before the 1980s (odds ratio: 1.90, 95% CI:
      1.11; 3.22). CONCLUSIONS: We observed declining industrial noise levels,
      increased use of HPD and no significant impact on hearing thresholds from current
      ambient industrial noise levels, which indicated a successful implementation of
      Danish hearing conservation programs.

PMID- 29192621
TI  - Auditory Brainstem Response (ABR) Findings With Click and CE-Chirp Stimulations
      in Noise-Exposed Participants.

PMID- 29192622
TI  - Subdural empyema: Clinical presentations and management options for an uncommon
      neurosurgical emergency in a developing country.
AB  - BACKGROUND: Controversy regarding the best management strategy for subdural
      empyema (SDE) attests to the persisting poor outcomes for this uncommon life
      threatening intracranial suppurative process. Late presentation confounds the
      problem in developed countries. While craniotomy is commonly recommended, it is
      not always possible in late presentation with advanced morbidity. The aim of this
      study was to identify the pattern of clinical presentation and explore the
      outcomes following management of SDE using burr hole, aspiration, and drainage
      (BAAD) in resource poor settings. MATERIALS AND METHODS: This is a retrospective
      review of prospectively collected data of 18 patients presenting with SDE over a
      period of 10 years from two neurosurgical centers. Data was abstracted on
      patients' demographic characteristics, sources of SDE, clinical presentation and
      site of infection, methods of diagnosis, organisms isolated, treatments received,
      and outcome. Collected data was entered into the Statistical Package for the
      Social Sciences version 17 software and subjected to descriptive analysis for all
      variables. RESULTS: Majority of the patients presented late with Glasgow Coma
      Scale score GCS of 9/15. Altered sensorium was noted in 14 (77.8%) of the
      patients, 11 (61.1%) out of the 14 patients had <= grade 3 of Bannister and
      Williams level of consciousness. The mainstay of treatment for all patients was
      BAAD of abscess and administration of appropriate antibiotics. Fourteen patients
      (77.8%) were discharged on grade A of H.W. Mauser's grading system. Three
      mortalities were recorded only in patients who had grade 4 Bannister and Williams
      grading. CONCLUSION: BAAD is the near approximated option to standard craniotomy
      management in a limited resource facility and it has a very good clinical
      outcome. However, more studies are required to draw the final conclusion.

PMID- 29192623
TI  - Color recovery effect of different bleaching systems on a discolored composite
      resin.
AB  - BACKGROUND AND PURPOSE: Discoloration of resin-based composites is a commonly
      encountered problem, and bleaching agents may be used for the therapy of the
      existing discoloration. The purpose of this study was to investigate in vitro
      color recovery effect of different bleaching systems on the heavily discolored
      composite resin. MATERIALS AND METHODS: Fifty disk-shaped dental composite
      specimens were prepared using A2 shade nanohybrid universal composite resin (3M
      ESPE Filtek Z550, St. Paul, MN, USA). Composite samples were immersed in coffee
      and turnip juice for 1 week in each. One laser activated bleaching (LB) (Biolase
      Laserwhite*20) and three conventional bleaching systems (Ultradent Opalescence
      Boost 40% (OB), Ultradent Opalescence PF 15% home bleaching (HB), Crest 3D White
      [Whitening Mouthwash]) were tested in this study. Distilled water was used as
      control group. The color of the samples were measured using a spectrophotometer
      (VITA Easy shade Compact, VITA Zahnfabrik, Bad Sackingen, Germany). Color changes
      (DeltaE00) were calculated using the CIEDE2000 formula. Statistical analyses were
      conducted using paired samples test, one-way analysis of variance, and Tukey's
      multiple comparison tests (alpha = 0.05). RESULTS: The staining beverages caused
      perceptible discoloration (DeltaE00 > 2.25). The color recovery effect of all
      bleaching systems was statistically determined to be more effective than the
      control group (P < 0.05). Although OB group was found as the most effective
      bleaching system, there was no statistically significant difference among HB, OB,
      and LB groups (P > 0.05). CONCLUSION: Within the limitation of this in vitro
      study, the highest recovery effect was determined in office bleaching system
      among all bleaching systems. However, home and laser bleaching systems were
      determined as effective as office bleaching system.

PMID- 29192624
TI  - Role of trichloroacetic acid and gelfoam in closure of tympanic membrane
      perforations.
AB  - OBJECTIVE: The aim of the study was to study the closure of dry central type of
      tympanic membrane perforations by chemical cautery and improvement of hearing, to
      analyse the effect of Gelfoam on nonhealing small tympanic membrane perforations,
      and to examine the relevance of conservative means of closure of tympanic
      membrane perforations as an office procedure. MATERIALS AND METHODS: In this
      study, 100 patients attending the outpatient department were enrolled. Cautery of
      perforation margin was carried out with 50% trichloroacetic acid (TCA). After
      cautery, in small perforations less than 4 mm, a small piece of Gelfoam larger
      than the size of perforation was cut, impregnated with corticosteroid ointment,
      and carefully placed over the cauterized area under endoscopic visualization. In
      slightly larger perforations, that is, between 4 and 5 mm, after applying TCA to
      the margins of the perforation, a piece of Gelfoam larger than the size of
      perforation was soaked with corticosteroid ointment and placed in the middle ear
      cavity. RESULTS: Patients had relief from various symptoms, such as tinnitus,
      heaviness, and so on. There was some amount of auditory improvement in almost all
      the cases. It ranged from 5 to 23 dB. CONCLUSIONS: Cautery and patching of
      tympanic membrane perforation may be considered as the first-line management in
      the small- to medium-sized perforations before attempting the surgical closure.

PMID- 29192625
TI  - The force required to fracture endodontically roots restored with various
      materials as intra-orifice barriers.
AB  - OBJECTIVE: To evaluate the effect of various materials as intra-orifice barriers
      on the force required fracture roots. MATERIALS AND METHODS: One hundred-thirty
      five mandibular premolars were decoronated and prepared up to size #40. The root
      canals were filled and randomly divided into two control and seven experimental
      groups (n = 15), as follows: Positive control group (the intra-orifice barrier
      cavity was not prepared), negative control group (the intra-orifice barrier
      cavity was prepared, but not filled), filling using glass ionomer cement, nano
      hybrid composite resin, short fiber-reinforced composite, bulk-fill flowable
      composite, MTA Angelus, Micro Mega MTA or Biodentine. A fracture strength test
      was performed, and the data were analyzed using one-way ANOVA and Tukey's post
      hoc tests. RESULTS: Nano-hybrid composite, short fiber-reinforced composite, bulk
      fill flow able composite, and glass ionomer cement increased the force required
      fracture the roots compared to the positive and negative control groups (P <
      0.05). While MTA groups did not increase the force required fracture the roots
      compared to the control groups, Biodentine increased significantly. CONCLUSIONS:
      Within the limitations of the present study, the use of nano-hybrid composite,
      short fiber-reinforced composite, bulk-fill flowable composite, and glass ionomer
      cement as an intra-orifice barrier may be useful in reinforcing roots. MTA
      placement (MTA Angelus or Micro Mega MTA) did not significantly increase the
      fracture resistance of endodontically treated roots compared to the control
      groups, however Biodentine did.

PMID- 29192626
TI  - Neutrophil lymphocyte ratio predicts postoperative pain after orthognathic
      surgery.
AB  - BACKGROUND AND AIM: Postoperative pain is well known and usually disturbing
      complication of surgery. Inflammation plays an important role in the development
      and progression of postoperative pain. We aimed to investigate possible
      relationship between preoperatively measured neutrophil-lymphocyte ratio (NLR) -
      as an inflammation marker - and postoperative analgesic demand in patients
      underwent orthognathic surgery. MATERIALS AND METHODS: We retrospectively
      investigated medical and anesthesia records of 177 patients underwent
      orthognathic surgery. Demographical data, preoperative NLR, type of surgery,
      modified Mallampati score, difficulty degree of intubation, duration of surgery,
      and postoperative analgesic (tenoxicam - as the first drug of choice,
      paracetamol, tramadol, or pethidine) usage were recorded. A cutoff value of NLR
      >=2 was determined for inflammation threshold. Two groups (Group 1 NLR >=2, Group
      2 NLR <2) were compared for analgesic doses, numbers of patients needed analgesic
      treatment, and other parameters. RESULTS: Mean administered tenoxicam dose was
      significantly higher in Group 1 than in Group 2 (P < 0.0001). Further, ratio of
      patients treated with tenoxicam in Group 1 was significantly higher than that in
      Group 2 (chi2 = 4.779, P = 0.029). CONCLUSIONS: Preoperatively measured NLR may
      help to predict postoperative analgesic demand in patients undergoing
      orthognathic surgery, and thus sufficient postoperative pain control can be
      achieved with various preventive treatments taken at the perioperative period
      such as preemptive analgesia, local anesthetic administration at the end of
      surgery, or early administration of analgesics.

PMID- 29192627
TI  - Behavioural and anthropometric risk factors for diabetes mellitus among newly
      admitted undergraduates in a Nigerian University.
AB  - BACKGROUND: Type 2 diabetes mellitus (DM) is fast becoming a global epidemic, and
      its prevalence is increasing in children and young adults. The aim of the study
      was to identify young adults who had type 2 DM or impaired fasting glucose as
      well as those at risk of these conditions using anthropometric data and
      behavioral pattern. METHODOLOGY: Two hundred and twenty newly admitted
      undergraduates who were randomly selected during the registration process were
      involved in the study. Anthropometric parameters were measured while information
      on demographic details, medical history, and family history were obtained using a
      standard questionnaire. Fasting blood glucose was measured using the glucose
      oxidase method. RESULTS: Two hundred and seven (94%) participants had serum
      glucose within reference range, 10 (4.6%) had impaired fasting glucose, and 3
      (1.4%) had serum glucose> 7.1 mmol/L, which is indicative of DM. A large number
      (91.4%) of individuals engaged in physical activity equivalent to a walk of at
      least 30 min/day. Most of them (93.2%) had body mass index <25.0 while 6.8% were
      overweight. One hundred and three participants (46.8%) indicated that they eat 3
      or more servings of whole grain per day. CONCLUSION: Most of the participants are
      involved in healthy lifestyle. This has resulted in very low prevalence of
      impaired fasting glucose and type 2 DM among the group. It will be useful to
      follow up the group and note if they are able to maintain this trend since the
      risk of developing DM is known to increase with age.

PMID- 29192628
TI  - A comparative study of the oral microbiome compositions of healthy
      postmenopausal, premenopausal, and prepubertal Nigerian females, using 16s rrna
      metagenomics methods.
AB  - INTRODUCTION: There is a paucity of information on the oral microbiome
      compositions of Nigerians, mostly due to lack of appropriate molecular
      techniques. In this pilot study, we sought to determine and characterize the oral
      bacterial compositions of "healthy" females. MATERIALS AND METHODS: Oral samples
      were collected from three randomly selected females aged 56, 28, and 8 years. DNA
      was extracted and 16S rRNA V4 region was amplified using custom-barcoded primers
      before sequencing with Illumina MiSeq platform. Quantitative Insights into
      Microbial Ecology pipeline was used for 16S rRNA recognition. Distribution of
      taxonomic categories at different levels of resolution was done using the
      ribosomal RNA similarities to entries in the REFseq protein database. Diversity
      score was calculated based on the inverse Simpson's index. RESULTS: The inverse
      Simpson's diversity index for the postmenopausal, premenopausal, and prepubertal
      was 7.74, 6.95, and 7.42 respectively. A total of 12 phyla, 70 genera, and 85
      species were detected. Firmicutes followed by Proteobacteria, Actinobacteria,
      Bacteroidetes, and Fusobacteria dominated the oral microbiome of the subjects.
      Streptococcus thermophilus (33.19%) was the most abundance species in subject 1,
      while subject 2 was highly predominated by Haemophilus parainfluenzae (80.65%),
      and subject 3 was predominated by Haemophilus influenzae (23.05%). CONCLUSION:
      The study has revealed that bacteria with varying diversities colonized the
      subjects and it highlighted the importance of metagenomics in deciphering the
      oral bacterial compositions from females of different age groups. More studies
      are needed using metagenomics approach, to appreciate these bacterial organisms
      that are associated with health and disease in our environment.

PMID- 29192629
TI  - Prevalence of traumatic dental injuries and associated factors among 8 to 12
      years-old schoolchildren in Diyarbakir, Turkey.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to assess the prevalence of traumatic
      injuries of the permanent incisors in public primary schoolchildren from 8 to 12
      years old in South-Eastern Anatolia, Turkey. Additionally, the relationship
      between traumatic dental injuries, parents' education level, family income, size
      of incisal overjet and the presence of anterior open bite were examined.
      MATERIALS AND METHODS: Data were collected through oral examinations and
      structured interviews, and included socio-economic indicators. A total of 2907
      children of both genders (1498 boys, 1409 girls) were included in the study. The
      response rate was 97%. RESULTS: The prevalence of dental injuries was 4.6% (n =
      135). The highest frequency of trauma in permanent teeth was observed at the age
      of 12 (8%). Boys experienced more dental injuries than girls, 5.9% and 3.3% (p =
      0.001), respectively. The most commonly reported cause of injuries to the
      permanent incisors was falls (71.8%), followed by collision with objects or
      people (17.8%). Maxillary central incisors were the most affected by dental
      injuries (154, 84.6%). The most common crown fracture was in enamel only (67.58%)
      followed by crown fracture of enamel and dentin (22.52%). CONCLUSION: Socio
      economic indicators and parents' level of education were not statistically
      significantly associated with the occurrence of traumatic dental injuries.
      Factors associated with increased risk of dental injuries in permanent teeth were
      age, gender, having an incisal overjet greater than 5mm and anterior open bite.

PMID- 29192630
TI  - Diagnostic utility of alpha-fetoprotein and des-gamma-carboxyprothrombin in
      nigerians with hepatocellular carcinoma.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) and Des-gamma-carboxyprothrombin (DCP) have
      been extensively studied as biomarkers for the diagnosis of and prognostication
      in hepatocellular carcinoma (HCC). However there are only few reports on the
      clinical characteristics of hepatocellular carcinoma in relation to the
      combination of the two tumor markers in hepatitis B virus-related HCC. AIM: The
      aim of this study was to investigate the clinical characteristics of HBV-related
      HCC in relation to different sets of AFP and DCP values. METHODS: Sixty-two
      patients with untreated HCC were studied. The positive value of AFP was set at 20
      1U/L while DCP positive value was set at 150 mAU/ml. Patients were divided into
      three groups: Group 1(n=36) with AFP >= 20 IU/L and DCP >= 150 mAU/ml. Group
      2(n=24) with AFP <20 1U/L and DCP >= 150 mAU/ml. Group 3 (n=2) with AFP < 20 1U/L
      and DCP < 150 mAU/ml. There were no patients in group 4 meant for those with AFP
      >= 20 1U/L and DCP < 150 mAU/ml. Clinical and laboratory variables were compared
      among the groups. RESULTS: Clinical and laboratory variables were comparable
      among the groups with the exception of gender and values of serum alanine
      aminotransferase (ALT). Males were significantly more than females among the
      groups (p<0.03). ALT values were significantly different among the groups
      (p<0.006). Paired comparisons between the groups showed the mean values of serum
      ALT were significantly higher in group 2 than in group 1(p<0.003). The mean serum
      ALT values were also higher in group 2 than in group 3 (p <0.014). There was no
      significant difference between group 1 and group 3 (P = 0.124). CONCLUSION: HCC
      patients who are sero-positive for DCP and sero-negative for AFP have
      significantly higher levels of serum ALT; serum ALT levels may be of diagnostic
      importance in AFP-negative, HBV-related HCC patients.

PMID- 29192631
TI  - Intermittent testicular torsion.
AB  - OBJECTIVE: The aim of this study is to highlight the clinical characteristics of
      patients with intermittent testicular torsion and draw attention to this
      underreported condition. METHODS: Clinical and demographic data of all patients
      treated for intermittent testicular torsion from January 2007 to June 2015 were
      prospectively collected in a pro forma and analyzed. A diagnosis of intermittent
      torsion was made on the basis of recurrent scrotal pain, presence of abnormal
      testicular lie in otherwise normal testes, absence of urinary symptoms, and
      negative urine cultures. This diagnosis was confirmed by resolution of symptoms
      following bilateral orchidopexy. All patients had bilateral orchidopexy at the
      next operative day and were followed up for 12 months. RESULTS: Forty-five
      patients with a mean age of 20.9 years (+/-4.02) were seen within the study
      period. The left testis was more often involved than the right: 53.3% versus
      37.8%. The condition was bilateral in 4 patients (8.9%). A total of 84 testes
      were evaluated. Horizontal lie was the most common anomaly causing intermittent
      testicular torsion 49%, followed by the clapper-bell deformity 27.5%. Patients
      experienced a mean of 2.8 (+/-1.74) acute pain episodes before testicular
      fixation. Bilateral orchidopexy resulted in resolution of symptoms and
      preservation of testicular volume. CONCLUSION: Horizontal lie of the testis is
      the most common cause of intermittent testicular torsion. The condition is more
      common on the left than the right testis and is predominantly unilateral.
      Intermittent testicular pain in the presence of abnormal testicular lie should
      warrant a diagnosis of intermittent testicular torsion. Early bilateral
      orchidopexy is efficacious.

PMID- 29192632
TI  - Effect of different modes of erbium:yttrium aluminum garnet laser on shear bond
      strength to dentin.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of different surface
      treatments on the shear bond strength (SBS) of resin composites to dentin using
      total etch dentin bonding adhesives. MATERIALS AND METHODS: Sixty extracted human
      molars were flattened to obtain dentin surfaces. The samples were divided into
      three groups (n = 20): Group I: 37% phosphoric acid + optibond FL + resin
      composite; Group II: Erbium:yttrium aluminum garnet (Er:YAG) laser (medium short
      pulse [MSP] mode, 120 mJ/10 Hz) + optibond FL + resin composite; Group III:
      Er:YAG laser (quantum square pulse [QSP] mode, 120 mJ/10 Hz) + optibond FL +
      resin composite. After the specimens were prepared, the SBS test was performed at
      a crosshead speed of 0.5 mm/min. The fractured specimens were examined under a
      stereomicroscope to evaluate the fracture pattern. Statistical analyses were
      performed with one-way ANOVA and Tukey's honestly significant difference tests.
      One sample of treated dentin surface from each group was sputter-coated with
      gold, and scanning electron microscope (SEM) images were captured. RESULTS: Acid
      etching showed significantly higher SBS than the other groups (P < 0.05).
      However, the difference between Er:YAG MSP and QSP mode groups was not
      statistically significant (P > 0.05). SEM images of the acid-etched dentin
      surface showed opened dentinal tubule with a regular surface, but Er:YAG MSP mode
      treated surface was irregular. The surface treated with Er:YAG QSP mode
      represented wide dentinal tubules with a clean and flat surface. CONCLUSION:
      Using different modes (MSP and QSP) of Er:YAG laser for dentin surface treatment
      before application of total etch adhesives is still not an sufficient alternative
      compared to acid etching.

PMID- 29192633
TI  - Pattern of maxillofacial surgical conditions in North Central Nigeria: A 5-year
      experience of an indigenous surgical mission.
AB  - BACKGROUND: Several publications have presented pattern of maxillofacial surgical
      conditions based on data from hospital-based studies. The objective of this study
      is to present the spectrum of maxillofacial surgical conditions from the
      perspective of a community study. METHODS: This is a prospective study of all
      patients seen and treated from 2011 to 2016. The information obtained included
      the biodata, clinical history of the disease conditions, radiological result,
      histopathologic result, diagnosis, and treatment records. Data analysis was
      carried out using SPSS version 20.0. RESULTS: There was a total of 863 patients,
      male 464 (53.8%) and female 399 (46.2%). The male to female sex ratio was 1.16:1.
      The age range was 3 days to 76 years with a mean age (SD) 16.8 +/- 15.8 years.
      The spectrum of surgical conditions: facial clefts 492(57.0%); tumor and tumor
      like lesions 126(15.2%), trauma 6(0.7%), and others 48(5.5 %). The size of tumors
      ranged from 5 to 50.4 cm2 with a mean (SD) 21.6 +/- 11.9 cm2 and the duration of
      lesion ranged from 1 to 20 years with mean (SD) 8.7 +/- 6.0 years. A total of
      622(77.4) cases were operated within the study period with immediate jaw
      reconstruction in 5(0.8%) patients. Minor complications were recorded but there
      was no mortality. CONCLUSION: The spectrum of maxillofacial surgery from
      community-based data was associated with higher percentage of facial cleft as
      compared to hospital-based study that is associated with higher traumatic injury
      cases. High level of poverty, ignorance, and poor access to maxillofacial service
      have been identified as shortcomings in the management of the diseases. There is
      a need for pragmatic move to improve facility, training, enlightenment, and more
      funding of outreach programs.

PMID- 29192634
TI  - The Pattern of significant lesions found in computerized tomography scan of
      recurrent seizure patients at a center in Enugu, Nigeria.
AB  - INTRODUCTION: Seizures are common reasons for neurologic consultations and
      investigations. In the absence of magnetic resonance imaging, computerized
      tomography scanning of the brain is a reliable and cheaper alternative. Little is
      known about the pattern of brain lesions in patients with recurrent seizures in
      Nigeria. OBJECTIVES: To determine the pattern of significant intracerebral
      lesions in patients presenting with recurrent seizures in a tertiary hospital in
      Enugu. METHODS: All the medical and computer tomography records of patients with
      a clinical diagnosis of recurrent seizures were reviewed. The study duration was
      11 years (January 2003 to December 2013). Relevant data were obtained and
      statistical analysis was done using SPSS version 19 and GraphPad Prism 6.
      RESULTS: The diagnostic yield of CT was 55.1%. Twenty (9.3%) individuals had two
      lesions each. The significant findings were tumors (20.4%), encephalomalacia
      (18.9%) and strokes (7.7% (ischemic stroke, 4.1%, intracerebral hemorrhage, 3.1%,
      subarachnoid hemorrhage/intraventricular hemorrhage, 0.5%). Hydrocephalus (HCP)
      was found in 18 (9.2%) cases, and 30% of them occurred together with other
      lesions. The diagnostic yield increased with age reaching 84.4% from the age of
      60 years. Only patients with encephalomalacia were statistically older than those
      with normal imaging. CONCLUSION: Computed tomography scan has a high diagnostic
      yield, especially in elderly patients with recurrent generalized seizures. Brain
      tumors, encephalomalacia, and HCP are most common causes of recurrent seizures in
      the adults.

PMID- 29192636
TI  - Assessment of body perception, psychological distress, and subjective quality of
      life among obese and nonobese subjects in Turkey.
AB  - BACKGROUND: Obesity can lead to psychological, social, and medical problems that
      may negatively affect the quality of life Aim: In our study, we aimed to evaluate
      the body perception, psychological distress, and subjective quality of life of
      obese subjects in comparison with normal weighted ones. METHODS: A total of 494
      subjects, aged between 18 and 64 years, were included to the study. Patients with
      the body mass index (BMI) of >=18.5-24.9 kg/m2 were assigned to the control
      group; BMI >= 30 kg/m2 were assigned to the obese patient group. An ethical
      committee approval with protocol No. of 2011/242 was obtained from the Ethical
      Committee of Eskisehir Osmangazi University Faculty of Medicine. Interviews were
      performed two times with obese subjects in the 1st and the 6th month of weight
      loss program, once with the control group. Data identification form, the form
      which included the biochemical parameters, Trait Anxiety inventory, State anxiety
      scale, Quality of Life scale-Short Form [(SF-36)(QOL)], Multidimensional Body
      Self Relations Questionnaire (MBSRQ), Zung Depression Rating Scale, and Zung
      Anxiety Rating Scale were applied to participants. RESULTS: Obesity is more
      common in women. Obesity reduces the quality of life, negatively affects body
      perception, and triggers anxiety. Because of their body structure, obese
      individuals are exposed to social pressure and unethical attitudes. CONCLUSIONS:
      Both health risks and social implications of obesity are important. Further
      studies are needed to ethically evaluate the psycho-social problems caused by
      obesity.

PMID- 29192635
TI  - Is hemorrhage the reason in crimean-congo hemorrhagic fever patients with
      neurological signs and symptomsa.
AB  - PURPOSE: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease can
      result in mortality varying from 3.0% to 50.0%. In this study, we wished to
      discuss computed tomography (CT) findings together with clinical and laboratory
      findings in patients who had disease-related neurological signs. MATERIALS AND
      METHODS: The study included patients who were diagnosed with CCHF. Seventeen
      patients that had neurological signs were enrolled as the patient group. As a
      control group, 40 patients diagnosed with CCHF and did not have neurological
      signs were enrolled. Patients who had neurological signs were examined with brain
      CT. Radiological and clinical findings of both groups were compared. RESULTS:
      There were pathological findings in three patients while brain CT's of 14
      patients were evaluated as normal. Blood urea nitrogen, lactate dehydrogenase,
      creatine kinase, total bilirubin, neutrophil, activated partial thromboplastin
      time, and C-reactive protein levels were significantly higher in the group with
      neurological signs whereas platelet count and calcium levels were significantly
      lower in this group. Six of 57 patients died during the follow-up period. Six
      patients who died were in the group, in which central nervous system (CNS)
      imaging study was performed. CONCLUSION: As the presence of CNS signs is a bad
      prognostic indicator in CCHF, they should be investigated carefully.

PMID- 29192637
TI  - Predictors of Vitamin D deficiency in predialysis patients with stage 3-5 chronic
      kidney diseases in Southern China.
AB  - OBJECTIVE: Vitamin D status and risk factors of Vitamin D deficiency in chronic
      kidney disease (CKD) patients in China have been seldom reported before. In this
      study, we aim to investigate serum 25-hydroxyvitamin D [25(OH)D] status and find
      the predictors of Vitamin D deficiency in predialysis patients with Stage 3-5
      CKDs in Southern China. METHODS: In this retrospective cross-sectional study,
      hospitalized predialysis patients who were diagnosed of Stage 3-5 CKD and had
      taken measurement of serum 25(OH)D in a single center from January 2014 to June
      2015 were included. Patients were divided into Vitamin D deficiency group and
      nondeficiency group depending on the cutoff serum 25(OH)D value of 37 nmol/L.
      Clinical and biochemical parameters were collected and evaluated for predictors
      of Vitamin D deficiency by logistic regression. RESULTS: One hundred and fifty
      two patients were included in this study, of which 87 (57.2%) were in Vitamin D
      insufficiency state while 60 (39.5%) were in Vitamin D deficiency state. Serum
      25(OH)D levels of patients in Stage 4 and Stage 5 CKD were lower than that of
      patients in Stage 3 CKD (P = 0.002). It was discovered that female gender (odds
      ratio [OR] = 3.674; 95% confidence interval [CI], 1.607-8.396; P = 0.002), serum
      albumin level <30.0 g/L (OR = 6.816; 95% CI, 2.634-17.633; P < 0.001), and
      estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 (OR = 4.761; 95%
      CI, 1.353-16.754; P = 0.015) were independent predictors of Vitamin D deficiency.
      CONCLUSIONS: Vitamin D insufficiency and deficiency are common in predialysis
      patients with Stage 3-5 CKD in Southern China. Female gender, hypoalbuminemia
      with serum albumin level <30.0 g/L, and severe damaged renal function with eGFR
      <30 ml/min/1.73 m2 are independent predictors of Vitamin D deficiency in
      predialysis patients with Stage 3-5 CKD.

PMID- 29192638
TI  - Clinical outcomes after open locked intramedullary nailing of closed femoral
      shaft fractures for adult patients in a Nigerian Hospital.
AB  - BACKGROUND: Femoral shaft fractures are common injuries in adults. Closed locked
      intramedullary nailing is the recommended treatment for femoral shaft fractures
      due to its high union rate. OBJECTIVE: The objective of this study is to
      determine the outcome of management of closed femoral shaft fractures in adult
      patients, using open locked intramedullary nailing. PATIENTS AND METHODS: This is
      a prospective study which was carried out on all adult patients aged 16 years and
      above who presented within 2 weeks of sustaining closed femoral shaft fractures
      to the accident and emergency unit of a University Teaching Hospital in Nigeria
      from January 2013 to December 2013. Pathological fractures were excluded from the
      study. The procedure was carried out using standard techniques, and each patient
      was followed up for a minimum of 1 year. RESULTS: Forty-three patients were
      recruited into the study. They had a mean age of 36.9 +/- 11.7 years, with a male
      to female ratio of 2.9:1. The most common cause of closed femoral shaft fractures
      was road traffic crashes (95.3%), with motorcycle-related injuries found to be
      the highest type (56.1%). The rate of union in the study was 95.3%. The average
      time to radiological union was 14.0 +/- 1.2 weeks while the mean time to painless
      full weight bearing was 14.2 +/- 1.2 weeks. Among the complications encountered
      were broken nails (4.7%), infection, loosening of the distal screw, and limb
      length discrepancy (2.3% each). Using Thoresen's criteria, excellent results were
      obtained in 93% and poor results in 4.7% of patients. CONCLUSION: Open locked
      intramedullary nailing gives excellent clinical outcomes with high union and low
      complication rates in the management of closed femoral shaft fractures in adult
      patients.

PMID- 29192639
TI  - Intrathecal ropivacaine in cesarean delivery.
AB  - OBJECTIVE: The aim of the present study was to evaluate the optimum dose of
      ropivacaine by comparing three different dosing regimens of isobaric ropivacaine
      1% (naropin 10 mg/ml, Astra Zeneca) administered intrathecally and to demonstrate
      the effects of anesthesia in pregnant women scheduled for cesarean section.
      PATIENTS AND METHODS: Sixty ASA grade I-II patients were scheduled to undergo
      elective cesarean sections under spinal anesthesia. The patients were randomly
      assigned into three groups. Group 1 received 15 mg ropivacaine 1%, Group 2
      received 20 mg ropivacaine 1%, and Group 3 received 25 mg ropivacaine 1%.
      RESULTS: Intraoperative hemodynamic variables were not significantly different
      between the three groups, and sensory block time, motor block time and time to
      reach maximal sensory block time, and motor block time were similar between the
      three groups. The time to two-segment regression of sensory block was longer in
      Group 3 compared to other groups, and the difference was statistically
      significant (p < 0.05). The motor block time was longer with higher doses of
      ropivacaine; however, the difference was not statistically significant.
      CONCLUSION: Ropivacaine administration produced rapid induction of anesthesia and
      satisfactory anesthesia level, ropivacaine 15 mg and 20 mg dosing regimens are
      satisfactory for spinal anesthesia.

PMID- 29192640
TI  - Axial length/corneal radius of curvature ratio and refractive status in an adult
      Nigerian population.
AB  - AIM/BACKGROUND: Associations between axial length (AL) to corneal radius of
      curvature (CR) ratio and refractive status in a healthy Nigerian adult population
      were studied. MATERIALS AND METHODS: Healthy students and members of staff of
      Obafemi Awolowo Teaching Hospitals Complex, Ile-Ife, South West Nigeria, free of
      obvious ocular diseases except possible refractive errors were recruited.
      Consecutive consenting volunteers were recruited by simple random sampling and a
      proportionate sample of each population based on its representative fraction in
      the hospital community was recruited. The study was conducted between June and
      August 2011. Noncycloplegic objective refraction was done and spherical
      equivalent refraction (SER) of the right eyes was used for calculation. The AL,
      CR, and keratometric readings were measured with the IOL Master. The AL/CR ratio
      was calculated. The data were analyzed with statistical software package STATA
      13. RESULTS: Three hundred and fifty volunteers aged 18-60 years were studied.
      The mean +/- standard deviation of AL/CR and SER were 3.04 +/- 0.10 and -0.38 +/-
      1.42D, respectively. AL in myopia was significantly higher than in emmetropia and
      hypermetropia. There were no significant differences between CR in the refraction
      groups. Myopes had significantly higher AL/CR than nonmyopes. On controlling for
      age and gender, 1 mm increase in AL increased SER by -0.77D (95% confidence
      interval [CI] -0.91--0.64D) while a unit increase in AL/CR increased SER by 
      8.89D (95% CI -10.00--7.78D). Whereas AL accounts for 39% of variability in SER
      (P < 0.001), AL/CR accounts for 51% of the variability observed in SER (P <
      0.001). CONCLUSION: This study has further confirmed that the AL remains a strong
      determinant of refraction, but a derived factor AL/CR accounts for more variation
      in final refractive status than AL in isolation.

PMID- 29192641
TI  - Diabetes or hypertension as risk indicators for missing teeth experience: An
      exploratory study in a sample of Mexican adults.
AB  - BACKGROUND: To determine an exploratory estimation of the strength of type 2
      diabetes mellitus (T2DM) and hypertension diagnoses as risk indicators for
      missing teeth in a sample of Mexican adults. MATERIALS AND METHODS: A comparative
      cross-sectional study of sixty adult patients in a health center in Mexico
      included as dependent variable, the number of missing teeth (and having a
      functional dentition) and as independent variables, diagnoses for diabetes or
      hypertension, age, sex, maximum level of schooling, and tobacco use. Of the 60
      participants, 20 were diagnosed with T2DM, 13 with hypertension, and 27 were
      otherwise diagnosed as healthy in their most recent medical checkup. A negative
      binomial regression (NBR) model was generated. RESULTS: Mean age was 50.7 +/-
      16.2 and 50.0% were women. Mean number of missing teeth was 4.98 +/- 4.17. In the
      multivariate NBR model, we observed that individuals with T2DM had higher risk of
      more missing teeth (incidence rate ratios [IRRs] = 3.13; 95% confidence interval
      [CI] = 2.09-4.69), followed by those with hypertension (IRRs = 2.63; 95% CI =
      1.77-3.90). In addition, participants with current tobacco use were significantly
      more likely to have suffered tooth loss (P < 0.05) than those who were never
      smokers or former smokers, just like older participants (P < 0.05). CONCLUSIONS:
      T2DM and hypertension are independently associated with higher experience of
      missing teeth in an open adult population in Mexico. Future studies with a more
      sophisticated epidemiological design and encompassing a more detailed landscape
      of chronic diseases, type and length of use of long-term medications, and
      patterns of dental care use are needed to better delineate these associations.

PMID- 29192642
TI  - Importance of optical diagnosis in early gastric cancer: A case report of early
      gastric signet ring cell carcinoma.
AB  - Gastric signet ring cell carcinoma (SRCC) is a rare form of highly malignant
      adenocarcinoma. It is an epithelial malignancy characterized by the histologic
      appearance of more than 50% of cells as signet ring cells filled with mucin. The
      incidence of SRCC is rising,[1],[2] therefore, the diagnosis of these cancers in
      the early stage is important as it is the only stage that curative measures can
      be done. A 49-year-old female was hospitalized due to epigastric pain,
      postprandial bloating for 3 months. Upper gastrointestinal endoscopy with narrow
      band imaging (NBI) showed 1.5 cm lesion in the lesser curvature of the stomach
      with irregular pit pattern and accentuated vascularization of the surrounding
      mucosa. Histopathology confirmed the presence of more than 50% of the cells as
      signet ring cells. We report on the importance of optical diagnosis in early
      gastric cancer with the help of NBI, the subsequent patient management, and
      prognosis.

PMID- 29192643
TI  - Multiple primary tumors.
AB  - Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It
      is not very common, but the incidence has increased gradually since it was first
      described very many years ago. However, in spite of its increasing incidence, the
      presence of such primary malignancies in the breast and colon has been rare and
      far between, as against its presence in breast and lungs, both breasts, colon and
      stomach, two colonic sites, and endometrium and ovaries. It could be due to
      genetic disorders such as Li-Fraumeni syndrome in which case the affected
      individuals develop multiple cancers in childhood or early adulthood. This is,
      however, very rare. It could be due to metastasis of one cancer to another site.
      The challenge is making a correct diagnosis and giving the appropriate
      management. Erroneously handling one as a metastasis of the other and instituting
      management as such would be inappropriate. It is necessary to make proper
      clinical and histopathological diagnosis and to institute proper management. We
      report the case of a woman who had primary cancers involving rare organ
      combinations of the breast and ascending colon.

PMID- 29192644
TI  - Automated (Centrifugal) therapeutic plasma exchange option for guillain-barre
      syndrome: A report from Calabar, Nigeria.
AB  - Therapeutic plasma exchange (TPE) is performed frequently and effectively in
      developed countries, whereas the reverse is the case in developing countries.
      Guillain-Barre syndrome (GBS), synonymous with acute inflammatory demyelinating
      polyneuropathy, is an important indication for TPE, but this is rarely
      administered in the treatment of such patients in Nigeria due to lack of such
      automated facility, limited expertise, and high cost. This report therefore
      presents an uncommon case of GBS in which automated TPE was utilized in the
      management, with the aims of highlighting the current status and challenges of
      therapeutic apheresis services in Nigeria. A 42-year-old male presented with
      rapidly progressive (in an ascending fashion) paralysis of all four limbs within
      24 h without any preceding history of fever or other symptoms. Clinical
      examination revealed a young man, afebrile, not pale, and also not dehydrated.
      Central nervous system examination showed a conscious man, alert, and oriented in
      time, person, and place. There were no signs of meningeal irritation and the
      cranial nerves were grossly intact. There was no power in the limbs: global
      hypotonia and areflexia were noted on examination. However, he had intact sensory
      perceptions to touch and pain. Following a diagnosis of GBS, he was treated with
      four sessions of plasmapheresis and TPE. The TPE session was done using a
      discontinuous flow apheresis machine which exchanged one plasma volume (3 L of
      plasma) and 5% albumin used for replacement. The patient made gradual but steady
      recovery as return of power to the upper limbs and trunk started by the 2nd week
      of treatment. TPE is an important treatment modality in the management of GBS as
      well as several other conditions, and it is becoming increasingly available in
      Nigeria. However, it is still grossly underutilized, thus the need for more
      therapeutic apheresis facilities and trained personnel, in addition to concerted
      efforts to subsidize the cost of accessing the treatment.

PMID- 29192645
TI  - H19 lncRNA regulates keratinocyte differentiation by targeting miR-130b-3p.
AB  - Aberrant differentiation of keratinocytes has been demonstrated to be associated
      with a number of skin diseases. A growing number of studies have showed that long
      noncoding RNAs (lncRNAs) have an important part in gene regulation, however, the
      role of lncRNAs in keratinocyte differentiation remains to be largely unknown. In
      the present study, we demonstrated that lncRNA-H19 act as an endogenous 'sponge',
      which binds directly to miR-130b-3p and therefore inhibits its activity on Dsg1.
      MiR-130b-3p was illustrated to inhibit keratinocyte differentiation by targeting
      Dsg1. H19 regulates Dsg1 expression and the consequent keratinocyte
      differentiation through miR-130b-3p. Our study casts light on a novel regulatory
      model of keratinocyte differentiation, which may provide new therapeutic targets
      of skin diseases.

PMID- 29192646
TI  - Development of a novel histologic diagnostic algorithm for hepatic graft-versus
      host disease.
AB  - The histopathologic diagnosis of hepatic graft-versus-host disease post bone
      marrow and stem cell transplantation can be challenging, but timely and
      unambiguous diagnosis is essential for appropriate patient management. To address
      this diagnostic dilemma, we identified histologic features specific for hepatic
      graft-versus-host disease and developed a diagnostic algorithm. Two
      hepatopathologists blindly evaluated 40 liver biopsies from patients with
      clinically and biologically confirmed graft-versus-host disease, as well as 44
      controls, for percent bile duct loss, bile duct damage, intraepithelial
      lymphocytes, ductular reaction, acidophilic bodies/10 high power fields (HPF),
      cholestasis, portal and lobular inflammation, and endotheliitis. Compared with
      controls, graft-versus-host disease cases had significantly more bile duct loss
      (P<0.0001), bile duct damage (P=0.0002), cholestasis (P<0.0001), and acidophilic
      bodies/10 HPF (P=0.0006), as well as significantly less ductular reaction
      (P<0.0001). Significance was maintained with a drug-induced liver injury-only
      control group. No histologic differences were noted in acute versus chronic graft
      versus-host disease, nor cholestatic versus hepatitic types. An algorithm to
      predict likelihood of graft-versus-host disease was developed, with a three
      tiered scoring system: 1-2 not, 3-4 probable, and 5-8 unequivocal graft-versus
      host disease. This algorithm had a sensitivity of 93%, specificity of 93%, and
      accuracy of 92%. We identified histologic features with specificity for hepatic
      graft-versus-host disease and developed a simple algorithm for pathologists to
      predict its likelihood, distinguishing this critical diagnosis promptly from
      mimickers having vastly different treatments and prognoses.

PMID- 29192649
TI  - The histopathology of Erdheim-Chester disease: a comprehensive review of a
      molecularly characterized cohort.
AB  - Erdheim-Chester disease is a rare, non-Langerhans cell histiocytosis
      histologically characterized by multi-systemic proliferation of mature
      histiocytes in a background of inflammatory stroma. The disease can involve
      virtually any organ system; most commonly the bones, skin, retroperitoneum,
      heart, orbit, lung, and brain are affected. Although a histiocytic proliferation
      is the histological hallmark of the disease, a wide range of morphological
      appearances have been described as part of case studies or small series. A
      comprehensive review of histopathological features in clinically and molecularly
      defined Erdheim-Chester disease has yet to be characterized. To address this
      issue and help guide clinical practice, we comprehensively analyzed the
      pathological spectrum of Erdheim-Chester disease in a clinically and molecularly
      defined cohort. We reviewed 73 biopsies from 42 patients showing involvement by
      histiocytosis from a variety of organ systems, including bone (16),
      retroperitoneum (11), skin (19), orbit (6), brain (5), lung (6), cardiac
      structures (2), epidural soft tissue (3), oral cavity (2), subcutaneous soft
      tissue (2), and testis (2). In eight patients, one or more bone marrow biopsies
      were performed due to clinical indication and an accompanying myeloid neoplasm
      was detected in six of them. Thirty-eight cases were investigated for genetic
      abnormalities. Somatic mutations involving BRAF (25/38), MAP2K1 (6/38), ARAF
      (2/38), MAP2K2 (1/38), KRAS (1/38), and NRAS (1/38) genes were detected. One of
      the cases with a MAP2K1 mutation also harbored a PIK3CA mutation. We have
      observed marked heterogeneity in histology and immunophenotype, identified site
      specific features, overlap with other histiocytic and myeloid disorders and
      potential diagnostic pitfalls. We hope that broadening the spectrum of recognized
      pathologic manifestations of Erdheim-Chester disease will help practicing
      clinicians and pathologists to diagnose Erdheim-Chester disease early in the
      disease course and manage these patients effectively.

PMID- 29192648
TI  - Identification of clinically relevant cytomegalovirus infections in patients with
      inflammatory bowel disease.
AB  - Several lines of evidence indicate that cytomegalovirus infection can be
      substantially associated with onset of inflammatory bowel disease, especially in
      patients refractory to immunosuppressive treatment. As cytomegalovirus is widely
      spread in the population, here we present a quantitative detection system
      suitable to differentiate clinically relevant cytomegalovirus infection from
      common latent cytomegalovirus. Using a quantitative real-time PCR approach,
      cytomegalovirus viral load was evaluated in 917 formalin-fixed and paraffin
      embedded colon biopsy samples of 136 patients diagnosed with inflammatory bowel
      disease. Besides initial cytomegalovirus testing, the PCR system was also used to
      monitor therapy response after antiviral treatment. Cytomegalovirus DNA was
      detected in 37 patients (27%) with varying viral loads ranging from 5 to 8.7 *
      105 copies/105 cells. Thereof, 13 patients (35%) received an antiviral treatment
      with 12 of them going into remission (92%). Later, five patients displayed a
      relapse and three patients who agreed to restart antiviral treatment again showed
      positive therapy response. A retrospective comparison of viral loads with
      antiviral therapy response revealed a threshold of 600 cytomegalovirus copies/105
      cells as indicative for clinically relevant infection. Of note, sensitivity of
      cytomegalovirus detection by immunohistochemistry was found to be insufficient to
      reliably identify antiviral therapy responders. In conclusion, quantitative real
      time PCR using formalin-fixed biopsy samples is suitable for detection of
      cytomegalovirus infection in tissue samples of patients with inflammatory bowel
      disease. Moreover, it allows the definition of a viral load threshold, predictive
      for clinical relevance concerning antiviral therapy response.

PMID- 29192647
TI  - Implications of the tumor immune microenvironment for staging and therapeutics.
AB  - Characterizing the tumor immune microenvironment enables the identification of
      new prognostic and predictive biomarkers, the development of novel therapeutic
      targets and strategies, and the possibility to guide first-line treatment
      algorithms. Although the driving elements within the tumor microenvironment of
      individual primary organ sites differ, many of the salient features remain the
      same. The presence of a robust antitumor milieu characterized by an abundance of
      CD8+ cytotoxic T-cells, Th1 helper cells, and associated cytokines often
      indicates a degree of tumor containment by the immune system and can even lead to
      tumor elimination. Some of these features have been combined into an
      'Immunoscore', which has been shown to complement the prognostic ability of the
      current TNM staging for early stage colorectal carcinomas. Features of the immune
      microenvironment are also potential therapeutic targets, and immune checkpoint
      inhibitors targeting the PD-1/PD-L1 axis are especially promising. FDA-approved
      indications for anti-PD-1/PD-L1 are rapidly expanding across numerous tumor types
      and, in certain cases, are accompanied by companion or complimentary PD-L1
      immunohistochemical diagnostics. Pathologists have direct visual access to tumor
      tissue and in-depth knowledge of the histological variations between and within
      tumor types and thus are poised to drive forward our understanding of the tumor
      microenvironment. This review summarizes the key components of the tumor
      microenvironment, presents an overview of and the challenges with PD-L1
      antibodies and assays, and addresses newer candidate biomarkers, such as CD8+
      cell density and mutational load. Characteristics of the local immune contexture
      and current pathology-related practices for specific tumor types are also
      addressed. In the future, characterization of the host antitumor immune response
      using multiplexed and multimodality biomarkers may help predict which patients
      will respond to immune-based therapies.

PMID- 29192650
TI  - Intramucosal lipomas of the colon implicate Cowden syndrome.
AB  - Intramucosal lipomas are rare and easily overlooked by pathologists, despite
      their diagnostic significance for Cowden syndrome (PTEN hamartoma tumor
      syndrome), an inherited multiorgan cancer syndrome. Only 25-35% of patients
      harbor identifiable PTEN mutations, thus clinical features, like intramucosal
      lipomas, remain the mainstay of diagnosis. The significance and diagnostic
      approach to intramucosal lipomas have not been thoroughly addressed in the
      literature. Intramucosal lipomas are mimicked by pseudolipomatosis coli, an
      artifactual mucosal gas infiltration from endoscopic insufflation. This
      differential was investigated by morphology and S-100 immunohistochemistry.
      Twenty-five colonic intramucosal lipomas were identified from 176 archival
      gastrointestinal lipomas from 1998 to 2017. Controls included 40 submucosal
      lipomas and 30 pseudolipomatoses. S-100 immunohistochemistry on all 95 lesions
      confirmed delicate fat vacuole membranous and nuclear S-100 staining in lipomas
      absent from pseudolipomatoses. Differentiating morphology between intramucosal
      lipoma and pseudolipomatosis, respectively, included consistently large, regular
      fat vacuoles (92% vs 7%), associated spindle cells (80% vs 0%), and mucosal
      lymphoid aggregate involvement (12% vs 80%). Of the 25 intramucosal lipomas, five
      patients (20%) had confirmed Cowden syndrome (four with PTEN mutations). In four
      of these Cowden patients, the intramucosal lipoma was the index diagnostic
      lesion. Three (12%) intramucosal lipoma patients had additional clinical features
      associated with Cowden syndrome, but did not meet the diagnostic criteria.
      Sporadic-type intramucosal lipomas were identified in 17 patients (68%) without
      evidence of Cowden syndrome, including three with normal PTEN genetic testing. No
      distinguishing endoscopic or pathologic polyp features were identified between
      sporadic and syndromic intramucosal lipomas. These data provide evidence that
      intramucosal lipomas are important harbingers of Cowden syndrome, making up
      approximately one-third of this series, the largest in the literature. We also
      show for the first time that two-thirds of intramucosal lipomas are sporadic.
      Gastrointestinal pathologists, gastroenterologists, and geneticists should
      increase their awareness of this subtle but diagnosable lesion strongly
      associated with Cowden syndrome.

PMID- 29192651
TI  - Myeloid neoplasms with features intermediate between primary myelofibrosis and
      chronic myelomonocytic leukemia.
AB  - Monocytosis can develop during disease course in primary myelofibrosis simulating
      that seen in chronic myelomonocytic leukemia, and should not lead to disease
      reclassification. In contrast, at presentation, rare cases have clinical,
      morphologic, and molecular genetic features truly intermediate between primary
      myelofibrosis and chronic myelomonocytic leukemia. The taxonomy and natural
      history of these diseases are unclear. We identified cases which either: (1)
      fulfilled the 2008 World Health Organization criteria for primary myelofibrosis
      but had absolute monocytosis and, when available, chronic myelomonocytic leukemia
      related mutations (ASXL1, SRSF2, TET2) or (2) fulfilled criteria of chronic
      myelomonocytic leukemia but had megakaryocytic proliferation and atypia, marrow
      fibrosis, and myeloproliferative-type driver mutations (JAK2, MPL, CALR).
      Patients with established primary myelofibrosis who developed monocytosis and
      those with chronic myelomonocytic leukemia with marrow fibrosis were excluded. By
      combining the pathology databases of two large institutions, six eligible cases
      were identified. Patients were predominantly male and elderly with monocytosis at
      diagnosis (average 17.5%/2.3 * 103/MUl), organomegaly, primary myelofibrosis-like
      atypical megakaryocytes admixed with a variable number of chronic myelomonocytic
      leukemia-like hypolobated forms, variable myelodysplasia, marrow fibrosis and
      osteosclerosis. All had a normal karyotype and no myelodysplasia-associated
      cytogenetic abnormalities. Five of the patients in whom a more extensive
      molecular characterization was performed showed co-mutations involving JAK2 or
      MPL and ASXL1, SRSF2, TET2, NRAS, and/or KRAS. Disease progression has occurred
      in all and two have died. Rare patients present with features that overlap
      between primary myelofibrosis and chronic myelomonocytic leukemia and are thus
      difficult to classify based on current World Health Organization criteria.
      Biologically, these cases likely represent primary myelofibrosis with
      monocytosis, dysplasia, and secondary (non-driver) mutations at presentation.
      Alternatively, they may represent a true gray zone of neoplasms. Their clinical
      behavior appears aggressive and innovative therapeutic approaches may be
      beneficial in this particular subset.

PMID- 29192653
TI  - A Translational Model to Assess Sign-Tracking and Goal-Tracking Behavior in
      Children.

PMID- 29192652
TI  - ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a
      newly defined entity.
AB  - High-grade endometrial stromal sarcoma likely encompasses underrecognized tumors
      harboring genetic abnormalities besides YWHAE-NUTM2 fusion. Triggered by three
      initial endometrial stromal sarcomas with ZC3H7B-BCOR fusion characterized by
      high-grade morphology and aggressive clinical behavior, we herein investigate the
      clinicopathologic features of this genetic subset by expanding the analysis to 17
      such tumors. All of them occurred in adult women with a median age of 54 (range,
      28-71) years. They were predominantly based in the endomyometrium and
      demonstrated tongue-like and/or pushing myometrial invasion. Most were uniformly
      cellular and displayed haphazard fascicles of spindle cells with mild to moderate
      nuclear atypia. Myxoid matrix was seen in 14 of 17 (82%) tumors, and collagen
      plaques were seen in 8 (47%). The mitotic index was >=10 mitotic figures/10 high
      power fields (HPFs) in 14 of 17 (82%) tumors with a median of 14.5 mitotic
      figures/10 HPFs. No foci of conventional or variant low-grade endometrial stromal
      sarcoma were seen. All tumors expressed CD10 with only limited or absent desmin,
      SMA and/or h-caldesmon staining. ER and PR expression in >5% of cells was seen in
      4 of 12 (33%) tumors. Diffuse cyclin D1 and BCOR immunoreactivity was present in
      7 of 8 (88%) and 7 of 14 (50%) tumors, respectively. Fluorescence in situ
      hybridization or targeted RNA sequencing confirmed ZC3H7B-BCOR fusion in all
      tumors, including four and two previously diagnosed as myxoid leiomyosarcoma and
      undifferentiated uterine sarcoma, respectively. Limited clinical data suggest
      that patients present at higher stage and have worse prognosis compared with
      published outcomes in low-grade endometrial stromal sarcoma. Tumors with ZC3H7B
      BCOR fusion constitute a distinct group of endometrial stromal sarcomas with high
      grade morphology that should be distinguished from other uterine mesenchymal
      neoplasms that may demonstrate myxoid morphology.

PMID- 29192654
TI  - The Ketamine Metabolite 2R,6R-Hydroxynorketamine Blocks NMDA Receptors and
      Impacts Downstream Signaling Linked to Antidepressant Effects.

PMID- 29192655
TI  - The Promise of Genome Editing for Modeling Psychiatric Disorders.

PMID- 29192656
TI  - Integrating 'Omics' Approaches to Prioritize New Pathogenetic Mechanisms for
      Mental Disorders.

PMID- 29192657
TI  - Novel Synthetic Opioids and Overdose Deaths: Tip of the Iceberg?

PMID- 29192658
TI  - Selective Adenylyl Cyclase Type 1 Inhibitors as Potential Opioid Alternatives For
      Chronic Pain.

PMID- 29192659
TI  - Computational Approaches to Behavior Analysis in Psychiatry.

PMID- 29192660
TI  - Cross-Species Neurophysiological Biomarkers of Attentional Dysfunction in
      Schizophrenia: Bridging the Translational Gap.

PMID- 29192661
TI  - Setting the Legal Age for Access to Cannabis in Canada: Bridging Neuroscience,
      Policy, and Prevention.

PMID- 29192662
TI  - Cannabinoid Receptor 1 Positive Allosteric Modulators for Posttraumatic Stress
      Disorder.

PMID- 29192663
TI  - Opioidergic regulation of pain and pleasure in human social relationships.

PMID- 29192664
TI  - Aggression Addiction and Relapse: A New Frontier in Psychiatry.

PMID- 29192665
TI  - Modeling Non-Syndromic Autism with Human-Induced Pluripotent Stem Cells.

PMID- 29192666
TI  - Cognitive Signaling in Cerebellar Granule Cells.

PMID- 29192667
TI  - Cannabis and Cannabinoids: From Synapse to Society.

PMID- 29192669
TI  - Modulating Amygdala-Hippocampal Network Communication: A Potential Therapy for
      Neuropsychiatric Disorders.

PMID- 29192668
TI  - Innovative Therapeutic Intervention For Opioid Use Disorder.

PMID- 29192670
TI  - Medical Cannabis Research: Issues and Priorities.

PMID- 29192671
TI  - The Role of Mitochondrial Glutamate Metabolism in Cognitive Development and
      Disease.

PMID- 29192672
TI  - Toward a Translationally Relevant Preclinical Model of Cannabis Use.

PMID- 29192673
TI  - TRFH domain: at the root of telomere protein evolution?
AB  - Two articles in Cell Research focus on the structure-function relationships in
      the shelterin complex that binds to telomeres and is essential for their
      stability and functions. These studies concerning both mammalian and
      Schizosaccharomyces pombe proteins reveal unexpected structural conservation of a
      motif called TRFH (Telomeric Repeat Factors Homology) domain between several
      subunits in these complexes, providing a rationale for further dissection of the
      role of telomeres in chromosome stability, aging and cancer, and encouraging us
      to revisit the evolution of telomere proteins.

PMID- 29192675
TI  - Wild gut microbiota protects from disease.
AB  - Wild mice are genetically similar to laboratory mice, but have a distinct gut
      microbiota that protects from disease.

PMID- 29192674
TI  - Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway.
AB  - Short-chain fatty acids and their corresponding acyl-CoAs sit at the crossroads
      of metabolic pathways and play important roles in diverse cellular processes.
      They are also precursors for protein post-translational lysine acylation
      modifications. A noteworthy example is the newly identified lysine 2
      hydroxyisobutyrylation (Khib) that is derived from 2-hydroxyisobutyrate and 2
      hydroxyisobutyryl-CoA. Histone Khib has been shown to be associated with active
      gene expression in spermatogenic cells. However, the key elements that regulate
      this post-translational lysine acylation pathway remain unknown. This has
      hindered characterization of the mechanisms by which this modification exerts its
      biological functions. Here we show that Esa1p in budding yeast and its homologue
      Tip60 in human could add Khib to substrate proteins both in vitro and in vivo. In
      addition, we have identified HDAC2 and HDAC3 as the major enzymes to remove Khib.
      Moreover, we report the first global profiling of Khib proteome in mammalian
      cells, identifying 6 548 Khib sites on 1 725 substrate proteins. Our study has
      thus discovered both the "writers" and "erasers" for histone Khib marks, and
      major Khib protein substrates. These results not only illustrate the landscape of
      this new lysine acylation pathway, but also open new avenues for studying diverse
      functions of cellular metabolites associated with this pathway.

PMID- 29192676
TI  - GOTcha: lncRNA-ACOD1 targets metabolism during viral infection.
AB  - Long-noncoding RNAs (lncRNAs) are emerging as important regulators of cellular
      processes, but few have been functionally characterized in host-pathogen
      interactions. A recent report in Science demonstrates a mechanistic role for a
      novel lncRNA in directly binding an essential metabolic enzyme, glutamic
      oxaloacetic transaminase (GOT2); this interaction benefits viral replication via
      alteration of host metabolism.

PMID- 29192677
TI  - Avian influenza H7N9 viruses: a rare second warning.
AB  - Avian influenza A H7N9 viruses that emerged in China in 2013 have reappeared each
      year, causing more than 1 600 severe human infections. As these viruses have
      evolved in nature, they have gained some and can gain additional virulence
      determinants that enhance their risk for humans, underlining the urgent need to
      control and eradicate H7N9 viruses in China.

PMID- 29192678
TI  - Portending death in germinal centers - when B cells know their time is up.
AB  - B cells undergo stringent selection in germinal centers (GCs) for expression of
      high-affinity antibodies, however, mechanisms of negative selection of low
      affinity B cell clones remain elusive. A new study by Michel Nussenzweig's group
      published in Science leverages a new reporter system that marks pre-apoptotic GC
      B cells to dissect microanatomic regions of GCs and their role in affinity
      maturation.

PMID- 29192679
TI  - Post-LASIK exacerbation of granular corneal dystrophy type 2 in members of a
      chinese family.
AB  - PurposeThe post-LASIK exacerbation of corneal dystrophy, otherwise asymptomatic,
      is almost exclusively associated with the TGFBI gene mutations at codon 124 in
      exon 4 and codon 555 in exon 12. It is our intention to demonstrate that the pre
      operative genetic screening for TGFBI mutations should be mandatory for
      refractive surgery candidates.Patients and MethodsIn this study, we reviewed the
      proband's post-LASIK slit-lamp and in vivo confocal microscopy images and genetic
      testing results, and performed genetic testing on eleven additional members of
      the family to investigate the penetrance of corneal dystrophy in asymptomatic
      members who carry the mutation.ResultsThe proband demonstrated a post-LASIK
      exacerbation of Granular Corneal Dystrophy type 2 (GCD2), identified as a TGFBI
      R124H mutation. Three of the 11 family members tested positive for the same R124H
      mutation as the proband.ConclusionThe lesson learned from this case is that the
      genetic screening of TGFBI mutations must be incorporated into the pre-operative
      screening procedures to prevent exacerbation and recurrence, which eventually
      could lead to the need for a corneal transplant.

PMID- 29192680
TI  - Management of MRSA-positive eye swabs and the potential advantages of
      chloramphenicol availability in the United Kingdom.

PMID- 29192681
TI  - EDTA chelation for symptomatic band keratopathy: results and recurrence.
AB  - PurposeTo identify causes of symptomatic band keratopathy, and assess the results
      and long-term recurrence rates following chelation with topical ethylene-diamine
      tetra-acetic acid (EDTA).Patients and methodsA retrospective review of surgical
      logbooks identified patients managed by EDTA chelation for symptomatic band
      keratopathy from 2009 to 2015.ResultsWe identified 108 cases; 89 case notes were
      available for analysis. Most cases of band keratopathy were idiopathic (36%). The
      most commonly identified underlying diagnosis was long-term topical glaucoma
      therapy (27%). Median presenting visual acuity was 6/18 (range 6/6-NPL) with the
      visual axis affected in 97.8% of cases. Treatment involved corneal epithelium
      removal, recurrent application of topical EDTA, and subsequent debridement. The
      mean duration of the operation was 20 min (range 10-45). Mean initial follow-up
      time was 40 days, and the visual axis was clear in 97.8%. Visual acuity was
      maintained or improved in 79.8%, with 13.5% improving by two lines or more. The
      mean length of follow-up was 581 days (median 374, maximum 2438). Twenty-five
      eyes (28.1%) showed localised recurrence of calcium with a mean time of 546 days
      (median 374), but only four cases required repeat EDTA chelation. The median time
      between operations was 430 days. Thirty-two per cent of the recurrence cases were
      associated with hypotony or chronic presence of silicone oil.ConclusionsChelation
      of calcium with topical EDTA is a safe and effective treatment for band
      keratopathy. Visual acuity improves in most eyes and while the rate of recurrence
      is moderate, the need for retreatment is low (4.5% overall).

PMID- 29192682
TI  - Corneal collagen cross-linking in keratoconus: primum non nocere.

PMID- 29192683
TI  - Corneal thickness in uveal coloboma with microcornea.
AB  - PurposeTo evaluate the relationship between central corneal thickness (CCT) and
      horizontal corneal diameter (HCD) in eyes with uveal coloboma and
      microcornea.Patients and methodsAll adult patients with uveal coloboma having
      microcornea in at least one eye and seen between May 2014 and July 2016 at the
      cataract clinic of our tertiary eye care center were evaluated. The study group
      comprised 26 colobomatous eyes of 15 patients who had associated microcornea. The
      control group comprised eyes with uveal coloboma and normal-sized cornea (n=12
      eyes of 9 patients). The main outcome measure included the relationship between
      CCT and HCD in eyes with uveal coloboma and microcornea.ResultsThe mean HCD of
      the study and control groups was 6.97+/-1.28 and 11.39+/-0.67 mm, respectively.
      The mean central pachymetry of the study group was 668.4+/-40.2 MUm compared with
      555.3+/-41.8 MUm in the control group. In both the groups, CCT was negatively
      correlated with HCD (R=-0.62 in the study group and R=-0.72 in the control
      group).ConclusionsUveal colobomatous eyes with microcornea have thicker corneas
      compared with uveal colobomatous eyes with normal diameter corneas that have
      normal central corneal thickness. In all the eyes with uveal coloboma, there is a
      negative correlation between horizontal corneal diameter and central corneal
      thickness.

PMID- 29192684
TI  - Early deep anterior lamellar keratoplasty for fungal keratitis poorly responsive
      to medical treatment.
AB  - PurposeTo investigate the efficacy of early therapeutic deep anterior lamellar
      keratoplasty (DALK) in eradicating fungal keratitis that is poorly responsive to
      medical treatment.Patients and methodsTwenty-three eyes (23 patients) underwent
      early therapeutic DALK within 15 to 50 days from the onset of symptoms. The
      adopted eligibility criteria for early DALK included the following: active fungal
      keratitis affecting the optical zone with ulcer confined in the 6.00 mm central
      cornea; deeper than 150 MUm but not exceeding 300 MUm; and poorly responsive to
      medical treatment.ResultsThe big bubble technique was accomplished in 74% (17) of
      eyes, whereas manual dissection was performed in the remaining 26% (6) of eyes.
      Histopathological examination did not show any sign of fungal colonization in the
      peripheral and deep stromal lamellae in any case. All grafts were transparent
      postoperatively, and no recurrence of infection occurred. Median best spectacle
      corrected visual acuity significantly improved from 2.0 (1.0 interquartile range)
      logMAR to 0.1 (0.1 interquartile range) logMAR (P<0.01). The mean follow-up was
      32+/-10 months. Neither episode of rejection nor graft failure was noted during
      the follow-up period.ConclusionEarly DALK could represent a safe therapeutic
      approach to eradicate fungal keratitis that affects the optical zone and is
      poorly responsive to medical treatment.

PMID- 29192685
TI  - The role of keratoprostheses.

PMID- 29192686
TI  - Evidence summary: the relationship between oral health and dementia.
AB  - This is the fourth and final paper of a series of reviews undertaken to explore
      the relationships between oral health and general medical conditions, in order to
      support teams within Public Health England, health practitioners and policy
      makers. This review aimed to explore the most contemporary evidence on whether
      poor oral health and dementia occurs in the same individuals or populations, to
      outline the nature of the relationship between these two health outcomes and to
      discuss the implication of any findings for health services and future research.
      The review was undertaken by a working group comprising consultant clinicians
      from medicine and dentistry, trainees, public health and academic staff. Whilst
      other rapid reviews in the current series limited their search to systematic
      reviews, this review focused on primary research involving cohort and case
      control studies because of the lack of high level evidence in this new and
      important field. The results suggest that poor oral hygiene is associated with
      dementia, and more so amongst people in advanced stages of the disease.
      Suboptimal oral health (gingivitis, dental caries, tooth loss, edentulousness)
      appears to be associated with increased risk of developing cognitive impairment
      and dementia. The findings are discussed in relation to patient care and future
      research.

PMID- 29192687
TI  - Projected speciality career choices among undergraduate dental students in
      Scotland.
AB  - Background Despite increased numbers of dental specialists, around 90% of
      dentists in the UK continue to work in general practice. Previous research shows
      that undergraduate students indicate interest in speciality careers, however few
      studies have explored which specialties are of interest, when and why. The aim of
      this study was to explore whether Bachelor of Dental Surgery (BDS) undergraduates
      attending Glasgow Dental School (GDS) indicate a desire to pursue a speciality
      career, why, and the extent to which they feel prepared in this regard.Method We
      conducted an internet-based survey (response rate 81%; n = 331) of all GDS
      students between October and November 2016.Results One hundred and eighty-six
      students (56%) had decided to specialise. Seventy-eight percent of these students
      cited enjoyment of that service, or types of patient seen, as the single most
      influencing factor on their choice. Oral surgery was the most popular choice
      where one was indicated (35%), followed by orthodontics (26%). Just 14% of BDS4-5
      students felt sufficiently exposed to cases in their chosen speciality. A large
      majority (88%) said they would like information regarding speciality pathways at
      BDS3 or before.Conclusions Educators should provide undergraduate students with
      information about specialties in a structured way, so that they can consider
      available options.

PMID- 29192688
TI  - Fluoridation and attention deficit hyperactivity disorder - a critique of Malin
      and Till (2015).
AB  - A recent ecological study found a statistically significant association of
      attention deficit hyperactivity disorder (ADHD) prevalence in youth with exposure
      to fluoride in fluoridated water. However, it included only household income as a
      possible covariate. In contrast another study found a significant association of
      ADHD prevalence with residential altitude. A multiple regression analysis
      including water fluoridation extent, mean US state elevation and a number of
      possibly important social factors as covariates showed statistically significant
      associations of ADHD prevalence in 2011 with altitude and per capita personal
      income in 2009. There was no statistically significant association of ADHD with
      the exposure to fluoride when these covariates were included. The ADHD
      fluoridation study suffers from insufficient consideration of possible risk
      modifying factors but has been widely cited because its reported findings appear
      advantageous to political campaigns against community water fluoridation.

PMID- 29192689
TI  - Using learning outcomes in dental education.
AB  - Explicitly-stated learning outcomes are an expected, integral part of
      contemporary under- and postgraduate learning programmes in dentistry. Writing
      learning outcomes, however, can be challenging and undertaken with a risk of not
      understanding what is meant by them and what well-constructed outcomes are meant
      to do. Written badly, learning outcomes will not help capture the goals of
      educational interventions or, perhaps worse, they end up as nothing more than a
      complex, frustrating hoop-jumping exercise in both their conception and
      utilisation. Underlying misconceptions of the purpose of learning outcomes or how
      to develop them are likely contributors to this situation. We would argue that if
      one understands the background, construct and intended purpose of learning
      outcomes we are more likely to write them so that they can actually be applied
      and therefore used effectively.

PMID- 29192690
TI  - The relevance of alcohol to dental practice.
AB  - Alcohol is a very widely used drug which can cause dental disease and influence
      dental treatment. It is therefore important that dental professionals take an
      alcohol history from all patients and are aware of how to give alcohol reduction
      advice. This article discusses the impact of alcohol on oral health, including
      oral cancer, trauma, halitosis, tooth wear, periodontal disease and caries, with
      reference to the available literature. It also outlines current alcohol risk
      level advice and guidance regarding giving alcohol reduction advice in a dental
      setting.

PMID- 29192691
TI  - Patient understanding of commonly used oral medicine terminology.
AB  - Introduction Communication within the doctor-patient relationship is complex due
      to a variety of reasons; a patient's understanding may not correspond with the
      clinician's vocabulary, resulting in misunderstanding, anxiety and ill-informed
      decision making. We investigated the understanding of terminology commonly used
      in oral and maxillofacial surgery and oral medicine clinics.Methods We
      investigated patients' understanding using a questionnaire-based study in the out
      patient setting. Age, gender, first language and highest educational level were
      recorded. The questionnaire included multiple choice questions regarding
      patients' understanding of words as well as asking patients to define certain
      terms. Vocabulary included 'ulcer', 'blister', 'cancer', 'malignant' and
      'benign'.Results and conclusions Many patients have difficulty in understanding
      and explaining commonly used terminology. 'Blister' was the most commonly
      understood term, while 'benign' and 'lesion' were the least well understood.
      'Tumour' was mistakenly thought of as synonymous with 'malignancy' by over a
      third of patients. Understanding was better among those for whom English was
      their first language. It is essential that all clinicians modify their language
      appropriately during consultations in order to deliver information in a
      comprehensive manner, to educate patients on their condition thus enabling
      informed decision making by patients.

PMID- 29192692
TI  - Detecting the earliest radiological signs of bisphosphonate-related
      osteonecrosis.
AB  - Introduction Oral bisphosphonates are the most commonly prescribed anti
      resorptive drugs used in the treatment of osteoporosis, but osteonecrosis of the
      jaw is a serious complication. The early diagnosis of this destructive side
      effect is crucial in preventing excessive bone loss, pain and infection.Objective
      To aid dental practitioners in the early identification of bisphosphonate-related
      osteonecrosis of the jaw.Method A scoping review was carried out.Data sources We
      searched MEDLINE via OVID, EMBASE via OVID, Dentistry and Oral Sciences Source
      (DOSS), Proquest Dissertation and Theses Search, to identify references that
      described clinical and radiological findings in medication-related osteonecrosis
      of the jaw (MRONJ).Data selection Nineteen references mentioned the earliest
      radiological changes in MRONJ with a description of the observations and were
      included in the analysis.Data synthesis The radiographic signs included
      osteosclerosis/lysis, widening of the periodontal ligament and thickening of the
      lamina dura and cortex. To assess the quality of original data on which
      recommendations had been made, these 19 studies were subjected to a quality
      appraisal.Conclusion Using bone exposure as a criterion for diagnosis of MRONJ,
      leads to delayed diagnosis and a poor response to treatment. In those patients at
      risk of bone exposure with MRONJ, insufficient information is present in the
      literature to allow the general dental practitioner to reliably identify the
      radiographic features indicating imminent bone exposure. A well-designed
      prospective study is needed.

PMID- 29192693
TI  - Who tells a mother her baby has died? Communication and staff presence during
      stillbirth delivery and early infant death.
AB  - OBJECTIVE: Perinatal loss (stillbirth or early infant death) is often a sudden,
      unexpected event for families. We evaluated who communicates the loss to the
      parents and who is there for support at the delivery or death. STUDY DESIGN: We
      conducted a mail survey of 900 bereaved and 500 live-birth mothers to assess
      emotional, physical and reproductive health outcomes. RESULTS: We had a 44%
      response rate at 9 months after birth or loss from 377 bereaved mothers and 232
      with surviving infants. Bereaved women were less likely to have hospital staff or
      family members present at delivery. African-American (versus Caucasian) mothers
      were half as likely to have first heard about their stillbirth from a physician
      or midwife. CONCLUSION: This is the first large study documenting who
      communicates perinatal death to families and who is present for support.
      Hospitals should be aware that many bereaved families may lack support at
      critical times.

PMID- 29192694
TI  - Antenatal corticosteroids for the late preterm infant and agnotology.

PMID- 29192696
TI  - Advances in the synthesis of nitroxide radicals for use in biomolecule spin
      labelling.
AB  - EPR spectroscopy is an increasingly useful analytical tool to probe biomolecule
      structure, dynamic behaviour, and interactions. Nitroxide radicals are the most
      commonly used radical probe in EPR experiments, and many methods have been
      developed for their synthesis, as well as incorporation into biomolecules using
      site-directed spin labelling. In this Tutorial Review, we discuss the most
      practical methods for the synthesis of nitroxides, focusing on the tunability of
      their structures, the manipulation of their sidechains into spin labelling
      handles, and their installation into biomolecules.

PMID- 29192697
TI  - Mapping piezoelectric response in nanomaterials using a dedicated non-destructive
      scanning probe technique.
AB  - There has been tremendous interest in piezoelectricity at the nanoscale, for
      example in nanowires and nanofibers where piezoelectric properties may be
      enhanced or controllably tuned, thus necessitating robust characterization
      techniques of piezoelectric response in nanomaterials. Piezo-response force
      microscopy (PFM) is a well-established scanning probe technique routinely used to
      image piezoelectric/ferroelectric domains in thin films, however, its
      applicability to nanoscale objects is limited due to the requirement for physical
      contact with an atomic force microscope (AFM) tip that may cause dislocation or
      damage, particularly to soft materials, during scanning. Here we report a non
      destructive PFM (ND-PFM) technique wherein the tip is oscillated into
      "discontinuous" contact during scanning, while applying an AC bias between tip
      and sample and extracting the piezoelectric response for each contact point by
      monitoring the resulting localized deformation at the AC frequency. ND-PFM is
      successfully applied to soft polymeric (poly-l-lactic acid) nanowires, as well as
      hard ceramic (barium zirconate titanate-barium calcium titanate) nanowires, both
      previously inaccessible by conventional PFM. Our ND-PFM technique is versatile
      and compatible with commercial AFMs, and can be used to correlate piezoelectric
      properties of nanomaterials with their microstructural features thus overcoming
      key characterisation challenges in the field.

PMID- 29192695
TI  - Israel transcutaneous bilirubin nomogram predicts significant hyperbilirubinemia.
AB  - OBJECTIVE: We constructed a transcutaneous bilirubin (TcB) nomogram to represent
      major sectors of the Israeli population. We studied the risk of
      hyperbilirubinemia, defined as meeting the requirements for phototherapy, per
      percentile risk category. STUDY DESIGN: Newborns ?36 weeks gestation were tested
      daily for TcB, using Drager JM-103 devices, during birth hospitalization. A
      nomogram was constructed and divided into four risk groups and validated by
      calculating the need for phototherapy for each group. RESULTS: A total of 3303
      measurements were performed on 1059 consecutive newborns including Ashkenazi,
      Sephardic and mixed Ashkenazi/Sephardic Jews, Arab and Ethiopian Jewish.
      Phototherapy risk increased progressively and more than 100-fold, from 0/225 in
      the <40th percentile group through 27/120 (22.5%) for those >95th percentile
      (relative risk (95% confidence interval) 102 (6 to 1669) for those >95th
      percentile compared with those <40th percentile). The optimal risk for
      discriminating the need for phototherapy was >75th percentile (sensitivity 93.33,
      specificity 59.47). CONCLUSION: The risk of significant hyperbilirubinemia
      increased progressively with increasing percentile. Newborns >75th percentile
      groups are at high risk for phototherapy and should be closely monitored.

PMID- 29192698
TI  - Boron and nitrogen co-doped ordered microporous carbons with high surface areas.
AB  - Boron and nitrogen co-doped ordered microporous carbons with high surface areas
      are obtained by using NaY zeolite as a hard template and an ionic liquid, 1-ethyl
      3-methylimidazolium tetracyanoborate (EMIT), as a BN source. An acetylene-gas
      supply during a pyrolysis is effective to avoid the unfavourable reaction of
      zeolite and EMIT.

PMID- 29192699
TI  - Design and synthesis of a hybrid framework of indanone and chromane: total
      synthesis of a homoisoflavanoid, brazilane.
AB  - A chemical backbone of tetracyclic homoisoflavanoid natural products such as
      brazilin inspired us to design a new chemical scaffold, 6a,11b-dihydroindeno[2,1
      c]chromen-7(6H)-one, which is a hybrid structure of indanone and chromane. Pd
      catalyzed Suzuki-Miyaura cross-coupling of 4-chloro-2H-chromene-3-carbaldehydes
      with (hetero)aryl boronic acids was employed as a means to introduce a wide
      variety of (hetero)aryl groups as the D ring and intramolecular Friedel-Crafts
      acylation was utilized to construct the C ring of this skeleton. Total synthesis
      of the natural product, brazilane, was also demonstrated via this new chemical
      framework.

PMID- 29192700
TI  - A small molecule for theraNOstic targeting of cancer cells.
AB  - Thera/NO - a small molecule that is activated by hydrogen peroxide to generate
      nitric oxide (NO) and a fluorescence signal is reported. Using cancer and primary
      cells, we show that Thera/NO preferentially releases NO in cancer cells, which
      can trigger DNA damage and cell death in them. The coupled fluorescence signal
      facilitated tracking the NO release in living cells without collateral
      consumption of NO.

PMID- 29192702
TI  - First-principles study of a MXene terahertz detector.
AB  - 2D transition metal carbides, nitrides, and carbonitrides called MXenes have
      attracted increasing attention due to their outstanding properties in many
      fields. By performing systematic density functional theory calculations, here we
      show that MXenes can serve as excellent terahertz detecting materials. Giant
      optical absorption and extinction coefficients are observed in the terahertz
      range in the most popular MXene, namely, Ti3C2, which is regardless of the
      stacking degree. Various other optical properties have been investigated as well
      in the terahertz range for in-depth understanding of its optical response. We
      find that the thermoelectric figure of merit (ZT) of stacked Ti3C2 flakes is
      comparable to that of carbon nanotube films. Based on excellent terahertz
      absorption and decent thermoelectric efficiency in MXenes, we finally suggest the
      promise of MXenes in terahertz detection applications, which includes terahertz
      bolometers and photothermoelectric detectors. Possible ZT improvements are
      discussed in large-scale MXene flake films and/or MXene-polymer composite films.

PMID- 29192703
TI  - The direct and highly diastereoselective synthesis of 3,4-epoxy-2-piperidones.
      Application to the total synthesis and absolute configurational assignment of
      3alpha,4alpha-epoxy-5beta-pipermethystine.
AB  - The substrate-controlled asymmetric total synthesis and absolute configurational
      assignment of biologically active 3alpha,4alpha-epoxy-5beta-pipermethystine, a
      minor component in the aerial parts of kava, has been achieved by featuring, as a
      key step, the environmentally friendly and direct synthesis of 2,3-epoxyamides
      from allyl amines. By using the chiron approach, first a carbohydrate-derived
      dehydropiperidine was prepared and subjected to a stereoselective tandem C
      H/C[double bond, length as m-dash]C oxidation reaction. In this attempt, the
      required alpha,alpha-trans-epoxy-2-piperidone skeleton of the kava metabolite
      precursor was not achieved, although the tandem oxidation was highly
      stereoselective. However, starting from non-carbohydrate 3-hydroxy-4,5
      dehydropiperidine, and using the same tandem oxidation, the target intermediate
      was obtained in high yield and complete unprecedented anti-stereoselectivity.
      Since the proposed mechanistic course of this tandem oxidation implies the
      transient formation of an alpha,beta-unsaturated amide followed by the subsequent
      epoxidation reaction, this second approach supports the previously established
      biotransformation proposal of (-)-pipermethystine to (-)-3alpha,4alpha-epoxy
      5beta-pipermethystine.

PMID- 29192701
TI  - Aptamer-mediated selective delivery of a cytotoxic cationic NHC-Au(i) complex to
      cancer cells.
AB  - A novel cationic NHC-Au(i) complex was synthesized and studied for its antitumor
      activity. For all the cell lines tested, cationic NHC-Au(i) complex 2 shows much
      higher cytotoxicity than its neutral analogue 1. To achieve selective cancer cell
      targeting, complex 2 was covalently conjugated to aptamer AS1411, a DNA aptamer
      with strong binding affinity for nucleolin. The successful conjugation was
      confirmed by HPLC, gel electrophoresis, fluorescence spectroscopy and UV-Vis
      absorption. Conjugate AS1411-2 was then examined for its specific targeting and
      binding ability towards cancer cells over human normal cells using flow cytometry
      analysis and confocal microscopy. The cytotoxicity of AS1411-2 was then estimated
      by MTS assay. It was found that AS1411-2 exhibits higher activity than complex 2
      towards targeted cells. Importantly, AS1411-2 exhibits much lower cytotoxicity
      towards healthy normal cell lines. Concurrently, the control groups without the
      AS1411 aptamer or without the NHC-Au(i) complex do have significant impact on
      cancer cell viability.

PMID- 29192704
TI  - Quantitative structure-activity relationships for primary aerobic biodegradation
      of organic chemicals in pristine surface waters: starting points for predicting
      biodegradation under acclimatization.
AB  - Microbial biomass and acclimation can affect the removal of organic chemicals in
      natural surface waters. In order to account for these effects and develop more
      robust models for biodegradation, we have compiled and curated removal data for
      un-acclimated (pristine) surface waters on which we developed quantitative
      structure-activity relationships (QSARs). Global analysis of the very
      heterogeneous dataset including neutral, anionic, cationic and zwitterionic
      chemicals (N = 233) using a random forest algorithm showed that useful
      predictions were possible (Qext2 = 0.4-0.5) though relatively large standard
      errors were associated (SDEP ~0.7). Classification of the chemicals based on
      speciation state and metabolic pathway showed that biodegradation is influenced
      by the two, and that the dependence of biodegradation on chemical characteristics
      is non-linear. Class-specific QSAR analysis indicated that shape and charge
      distribution determine the biodegradation of neutral chemicals (R2 ~ 0.6), e.g.
      through membrane permeation or binding to P450 enzymes, whereas the average
      biodegradation of charged chemicals is 1 to 2 orders of magnitude lower, for
      which degradation depends more directly on cellular uptake (R2 ~ 0.6). Further
      analysis showed that specific chemical classes such as peptides and organic
      halogens are relatively less biodegradable in pristine surface waters, resulting
      in the need for the microbial consortia to acclimate. Additional literature data
      was used to verify an acclimation model (based on Monod-type kinetics) capable of
      extrapolating QSAR predictions to acclimating conditions such as in water
      treatment, downstream lakes and large rivers under MUg L-1 to mg L-1
      concentrations. The framework developed, despite being based on multiple
      assumptions, is promising and needs further validation using experimentation with
      more standardised and homogenised conditions as well as adequate characterization
      of the inoculum used.

PMID- 29192705
TI  - Correction: Synthesis of Z-alkenes via visible light promoted photocatalytic E ->
      Z isomerization under metal-free conditions.
AB  - Correction for 'Synthesis of Z-alkenes via visible light promoted photocatalytic
      E -> Z isomerization under metal-free conditions' by Wenbin Cai et al., Chem.
      Commun., 2017, DOI: .

PMID- 29192706
TI  - Estimation of electric field effects on the adsorption of molecular superoxide
      species on Au based on density functional theory.
AB  - Superoxide species are key intermediates in the oxygen reduction reactions (ORR)
      that occur at the cathodes of aprotic metal-air batteries. Herein we report a DFT
      study of the effects of an externally applied electric field (epsilon) on the
      stability of various molecular superoxide species, including MO2 (M = Li, Na, K)
      and O2-, on gold surfaces, which shows that the stability of such species on Au
      electrodes can be materially affected by the presence of an electric field and
      solvent molecules, suggesting that such effects should be included in the first
      principles modeling of cathode reactions in metal-O2 cells. In the epsilon range
      of +/-0.4 V A-1, the stability of MO2 species is found to vary by up to |0.4| eV
      on Au(111) and |0.2| eV on Au(211) in vacuo, which is larger than the field
      effects on the stability of O and OH, key intermediates in the ORR by hydrogen.
      An aprotic solvent such as dimethyl sulfoxide (DMSO), considered here via the
      inclusion of explicit DMSO molecules above the Au surfaces, stabilizes all three
      MO2 species at zero fields and amplifies the field effects on the stability of
      MO2, on both Au surfaces. The variations in the stability of the molecular MO2
      species with epsilon, which have small polarizabilities, are closely approximated
      by the first-order Stark effect (MU0.epsilon, where MU0 is the static surface
      dipole moment induced by adsorption at epsilon = 0 V A-1). The superoxide anion
      (O2-) that has been identified on an under-coordinated Au site has a larger
      polarizability than the MOx species and a MU0 that is opposite in sign to those
      of the metal MO2 species, which results in larger errors by the first-order
      approximation, although its stability varies only moderately under positive
      electric fields of up to 0.4 V A-1.

PMID- 29192707
TI  - Polyphenol-enriched berry extracts naturally modulate reactive proteins in model
      foods.
AB  - Healthy foods like polyphenol-rich berries and high quality edible proteins are
      in demand in today's functional food marketplace, but it can be difficult to
      formulate convenient food products with physiologically-relevant amounts of these
      ingredients and still maintain product quality. In part, this is because proteins
      can interact with other food ingredients and precipitate destabilizing events,
      which can disrupt food structure and diminish shelf life. Proteins in foods can
      also interact with human receptors to provoke adverse consequences such as
      allergies. When proteins and polyphenols were pre-aggregated into stable
      colloidal particles prior to use as ingredients, highly palatable food
      formulations (with reduced astringency of polyphenols) could be prepared, and the
      overall structural properties of food formulations were significantly improved.
      All of the nutritive and phytoactive benefits of the proteins and concentrated
      polyphenols remained highly bioavailable, but the protein molecules in the
      particle matrix did not self-aggregate into networks or react with other food
      ingredients. Both the drainage half-life (a marker of structural stability) and
      the yield stress (resistance to flow) of model foams made with the protein
      polyphenol particles were increased in a dose-dependent manner. Of high
      significance in this complexation process, the reactive allergenic epitopes of
      certain proteins were effectively blunted by binding with polyphenols,
      attenuating the allergenicity of the food proteins. Porcine macrophages produced
      TNF-alpha proinflammatory cytokine when provoked with whey protein, but, this
      response was blocked completely when the cells were stimulated with particles
      that complexed whey protein with cinnamon-derived polyphenols. Cytokine and
      chemokine production characteristic of allergic reactions were blocked by the
      polyphenols, allowing for the potential creation of hypoallergenic protein-berry
      polyphenol enriched foods.

PMID- 29192708
TI  - On the combustion mechanisms of ZrH2 in double-base propellant.
AB  - Metal hydrides are regarded as a series of promising hydrogen-supplying fuel for
      solid rocket propellants. Their effects on the energetic and combustion
      performances of propellants are closely related to their reaction mechanisms.
      Here we report a first attempt to determine the reaction mechanism of ZrH2, a
      high-density metal hydride, in the combustion of a double-base propellant to
      evaluate its potential as a fuel. ZrH2 is determined to possess good resistance
      to oxidation by nitrocellulose and nitroglycerine. Thus its combustion starts
      with dehydrogenation to generate H2 and metallic Zr. Subsequently, the newly
      formed Zr and H2 participate in the combustion and, especially, Zr melts and then
      combusts on the burning surface which favors the heat feedback to the propellant.
      This phenomenon is completely different from the combustion behavior of the
      traditional fuel Al, where the Al particles are ejected off the burning surface
      of the propellant to get into the luminous flame zone to burn. The findings in
      this work validate the potential of ZrH2 as a hydrogen-supplying fuel for double
      base propellants.

PMID- 29192709
TI  - Conformational disorder and solvation properties of the key-residues of a protein
      in water-ethanol mixed solutions.
AB  - A small number of key-residues in a protein sequence play vital roles in the
      function, stability, and folding of the protein. The nonuniform conformational
      disorder of a small protein Chymotrypsin Inhibitor 2 (CI2) and its secondary
      segments has been quantified in the ethanol governed temperature induced
      unfolding process by estimating its change in configurational entropy in several
      water-ethanol mixed solutions. Such calculations further assist us in identifying
      the key-residues, from where the unfolding of the protein was initiated. Our
      findings match well with the reported experimental results. We then make an
      attempt to explore the properties of the solvent water and ethanol around the key
      residues of the protein in its folded and unfolded forms at ambient temperature
      to identify the individual role of ethanol and water in the protein unfolding. We
      find that the key-residues of the unfolded protein are in good contact with both
      water and ethanol as compared to those of the folded protein. In the presence of
      ethanol, water molecules are noticed to form a rigid structurally bound solvation
      layer around the key-residues of the protein, irrespective of its conformational
      state. The restricted translational motion and prominent caging effect of the
      water and ethanol molecules present around the key-residues of the unfolded
      protein are a signature of the existence of a rigid mixed water-ethanol layer as
      compared to that around the folded protein. Furthermore, comparable restricted
      structural relaxation of the key-residue-water and key-residue-ethanol hydrogen
      bonds in the unfolded protein as compared to that in the folded one implies that
      the formation of a strong long-lived hydrogen bonding environment nourishes the
      unfolding process. We believe that our findings will shed light to several co
      solvent governed unfolding processes of a protein in general.

PMID- 29192710
TI  - Dynamical properties of EMIM-SCN confined in a SiO2 matrix by means of 1H NMR
      relaxometry.
AB  - 1H nuclear magnetic resonance relaxometry is applied to investigate the
      translational and rotational dynamics of ionogels composed of an ionic liquid
      (IL): 1-ethyl-3-methyl-imidazolium-thiocyanate (EMIM-SCN) confined in a
      nanoporous SiO2 matrix. The relaxation studies were performed in the frequency
      range of 4 kHz-40 MHz and the temperature range of 223-248 K for different
      concentrations of the IL; the ratio (no. of moles of IL/no. of moles of SiO2)
      yields: 1/2, 3/5 and 7/10. A thorough analysis of this large set of experimental
      data was performed assuming the existence of two fractions of the liquid: a core
      fraction (near the pore center) and a surface fraction (near the confining
      walls). It was shown for all concentrations that the confinement does not
      significantly affect the translational motion near the pore center compared to
      the dynamics in bulk. The diffusion coefficients in the surface fraction are
      considerably smaller compared to the core fraction (from one to two orders of
      magnitude) and the difference becomes larger with increasing temperature. The
      diffusion coefficients become smaller for higher concentrations - this effect is
      not large, but visible. Very importantly, it was shown that, despite the
      interactions with the surface, the diffusion in the surface fraction remains of
      3D character. As far as rotational dynamics in the surface fraction is concerned,
      it slows down compared to the bulk (and the core fraction), but this effect is of
      the order of factor 2-3.

PMID- 29192711
TI  - Nitrification in a soil-aquifer treatment system: comparison of potential
      nitrification and concentration profiles in the vadose zone.
AB  - The oxidation of ammonium in the vadose zone of soil aquifer systems is discussed
      and examined by detailed analysis of the depth profiles of dissolved oxygen,
      nitrate and ammonium concentrations in the vadose zone of a soil-aquifer
      treatment (SAT) system of a municipal wastewater treatment system of the Tel Aviv
      metropolitan area. Nitrification kinetics and ammonium adsorption capacity
      studies show that neither the nitrification rate nor the ammonium adsorption
      capacity controls the capacity of the Shafdan SAT system for ammonium removal.
      Evaluation of the ammonium adsorption capacity of the soil reveals that under
      ideal conditions, a depth of less than 50 cm is sufficient to adsorb all the
      ammonium supplied in a flooding cycle. In-field studies show that all the
      ammonium is concentrated within the first 80 cm of the vadose zone. A depth
      profile of the Potential Nitrification (P.N), a measure of the local amount and
      activity of nitrifiers, is presented for the first time in the vadose zone of a
      SAT system showing that there are sufficient nitrifiers to oxidize all the
      ammonia that is supplied in a flooding cycle within less than 2 h, under optimal
      microbiological conditions based on the existing nitrifiers and their spatial
      distribution. The biodegradation rate in the field corresponds to first order
      ammonium conversion with a kinetic coefficient of 8.0 +/- 0.2 d-1. Accordingly,
      the average measured rate was 8.6 +/- 5.8 mg NH4+-N per kg per d for in-field
      tests, which can be compared to the average P.N, with a value of 34.5 +/- 16.8 mg
      NH4+-N per kg per d. The results suggest that a SAT design, taking into account
      full ammonium removal capacity, is feasible and can rely on the evaluation of the
      ammonium adsorption capacity in the SAT soil, the ammonium input and the P.N of
      the equilibrated target soil under conditions simulating the operation of the
      infiltrating basins.

PMID- 29192712
TI  - Effects of the c-Si/a-SiO2 interfacial atomic structure on its band alignment: an
      ab initio study.
AB  - The crystalline-Si/amorphous-SiO2 (c-Si/a-SiO2) interface is an important system
      used in many applications, ranging from transistors to solar cells. The
      transition region of the c-Si/a-SiO2 interface plays a critical role in
      determining the band alignment between the two regions. However, the question of
      how this interface band offset is affected by the transition region thickness and
      its local atomic arrangement is yet to be fully investigated. Here, by
      controlling the parameters of the classical Monte Carlo bond switching algorithm,
      we have generated the atomic structures of the interfaces with various
      thicknesses, as well as containing Si at different oxidation states. A hybrid
      functional method, as shown by our calculations to reproduce the GW and
      experimental results for bulk Si and SiO2, was used to calculate the electronic
      structure of the heterojunction. This allowed us to study the correlation between
      the interface band characterization and its atomic structures. We found that
      although the systems with different thicknesses showed quite different atomic
      structures near the transition region, the calculated band offset tended to be
      the same, unaffected by the details of the interfacial structure. Our band offset
      calculation agrees well with the experimental measurements. This robustness of
      the interfacial electronic structure to its interfacial atomic details could be
      another reason for the success of the c-Si/a-SiO2 interface in Si-based
      electronic applications. Nevertheless, when a reactive force field is used to
      generate the a-SiO2 and c-Si/a-SiO2 interfaces, the band offset significantly
      deviates from the experimental values by about 1 eV.

PMID- 29192713
TI  - Combining the platinum(ii) drug candidate kiteplatin with 1,10-phenanthroline
      analogues.
AB  - Platinum complexes of the type [Pt(PL)(AL)]2+ where PL is a derivative of 1,10
      phenanthroline and AL is cis-1,4-diaminocyclohexane (1,4-dach), have been
      synthesised and characterised by ultraviolet spectroscopy, elemental
      microanalysis, nuclear magnetic resonance and X-ray crystallography. The calf
      thymus DNA binding affinity of these complexes was determined by isothermal
      titration calorimetry, revealing higher DNA affinity than their 1S,2S
      diaminocyclohexane analogues. In vitro cytotoxicity was assessed in eleven human
      cell lines, revealing unexpectedly low activity for the 1,4-dach complexes.

PMID- 29192714
TI  - 2-(2-Hydroxyphenyl)imidazole-based four-coordinate organoboron compounds with
      efficient deep blue photoluminescence and electroluminescence.
AB  - Two new four-coordinate organoboron compounds with 2-(2-hydroxyphenyl)imidazole
      derivatives as the chelating ligands have been synthesized. They possess high
      thermal stability and are able to form an amorphous glass state. Crystallographic
      analyses indicate that the differences in ligand structure cause the change of
      pipi stacking character. The CH2Cl2 solutions and thin films of these compounds
      display bright blue emission, and these compounds have appropriate HOMO and LUMO
      energy levels for carrier injection in OLEDs. By utilizing the good thermal and
      luminescent properties, as well as the proper frontier orbital energy levels,
      bright non-doped OLEDs with a simple structure have been realized. Notably, these
      simple devices show deep blue electroluminescence with the Commission
      Internationale de l'Eclairage (CIE) coordinate of ca. (0.16, 0.08), which is
      close to the CIE coordinate of (0.14, 0.08) for standard blue defined by the
      National Television System Committee. In addition, one of the devices exhibits
      good performance, showing brightness, current efficiency, power efficiency and
      external quantum efficiency up to 2692 cd m-2, 2.50 cd A-1, 1.81 lm W-1 and
      3.63%, respectively. This study not only provides good deep-blue emitting OLED
      materials that are rarely achieved by using four-coordinate organoboron
      compounds, but also allows a deeper understanding of the structure-property
      relationship of 2-(2-hydroxyphenyl)imidazole-based boron complexes, which
      benefits the further structural design of this type of material.

PMID- 29192715
TI  - Tissue or blood: which is more suitable for detection of EGFR mutations in non
      small cell lung cancer?
AB  - BACKGROUND: Many studies have evaluated the accuracy of EGFR mutation status in
      blood against that in tumor tissues as the reference. We conducted this
      systematic review and meta-analysis to assess whether blood can be used as a
      substitute for tumor tissue in detecting EGFR mutations. METHODS: Investigations
      that provided data on EGFR mutation status in blood were searched in the
      databases of Medline, Embase, Ovid Technologies and Web of Science. The detect
      efficiency of EGFR mutations in paired blood and tissues was compared using a
      random-effects model of meta-analysis. Pooled sensitivity and specificity and
      diagnostic accuracy were calculated by receiver operating characteristic curve.
      RESULTS: A total of 19 studies with 2,922 individuals were involved in this meta
      analysis. The pooled results showed the positive detection rate of EGFR mutations
      in lung cancer tissues was remarkably higher than that of paired blood samples
      (odds ratio [OR] = 1.47, p<0.001). The pooled sensitivity and specificity of
      blood were 0.65 and 0.91, respectively, and the area under the receiver operating
      characteristic curve was 0.89. CONCLUSIONS: Although blood had a better
      specificity for detecting EGFR mutations, the absence of blood positivity should
      not necessarily be construed as confirmed negativity. Patients with negative
      results for blood should decidedly undergo further biopsies to ascertain EGFR
      mutations.

PMID- 29192717
TI  - In vitro trials of a wearable artificial kidney (WAK).
AB  - BACKGROUND: This paper presents results of in vitro trials of a wearable
      artificial kidney (WAK). MATERIALS AND METHODS: To carry out the trials, a test
      bench was developed. It consisted of a patient imitator, a tubing set and
      measuring equipment. RESULTS: Our WAK can eliminate urea, uric acid and
      creatinine from spent dialysate with mean mass rates of 0.85 +/- 0.1 g/h, 0.10 +/
      0.04 g/h and 0.05 +/- 0.01 g/h, respectively. Concentrations of Na+, Cl- and
      Ca2+ ions were kept in the 10% range from initial values. We demonstrated that
      our WAK can operate for 38 hours without having to replace expendable materials.
      CONCLUSIONS: The WAK that we developed can eliminate metabolites from spent
      dialysis fluid with mass rates that are sufficient to maintain stable,
      physiologically normal metabolite concentrations in patients' blood.

PMID- 29192716
TI  - The cardiotomy reservoir - a preliminary evaluation of a new cell source for
      cardiovascular tissue engineering.
AB  - OBJECTIVES: Cell sources for cardiovascular tissue engineering (TE) are scant.
      However, the need for an ideal TE cardiovascular implant persists. We
      investigated the cardiotomy reservoir (CR) as a potential cell source that is
      more accessible and less ethically problematic. METHODS: CR (n = 10) were removed
      from the bypass system after surgery. Isolation was performed using different
      isolation methods: blood samples were taken from the cardiopulmonary bypass and
      centrifuged at low density. The venous filter screen was cut out and placed into
      petri dishes for cultivation. The spongelike filter was removed, washed and
      treated in the same way as the blood samples. After cultivation, cell lines of
      fibroblasts (FB) and endothelial cells (EC) were obtained for analysis. The cells
      were seeded on polyurethane patches and analyzed via scanning electron microscopy
      (SEM), Life/Dead assay and immunohistochemistry. RESULTS: No correlation between
      age, time of surgery and quality of cells was observed. The successful extraction
      of FB and was proven by positive staining results for TE-7, CD31 and vWF. Cell
      morphology, cytoskeleton staining and quantification of proliferation using WST-1
      assay resembled the cells of the control group in all ways. The topography of a
      confluent and vital cell layer after cell seeding was displayed by SEM analysis,
      Life/Dead Assay and immunohistochemistry. The establishment of an extracellular
      matrix (ECM) was proven by positive staining for collagen IV, laminin,
      fibronectin and elastin. CONCLUSIONS: Viable FB and EC cell lines were extracted
      from the CR after surgery. Easy access and high availability make this cell
      source destined for widespread application in cardiovascular tissue engineering.

PMID- 29192718
TI  - Corrosion of titanium: Part 2: Effects of surface treatments.
AB  - Titanium is well known as one of the most corrosion-resistant metals. However, it
      can suffer corrosion attacks in some specific aggressive conditions. To further
      increase its corrosion resistance, it is possible either to modify its surface,
      tuning either thickness, composition, morphology or structure of the oxide that
      spontaneously forms on the metal, or to modify its bulk composition. Part 2 of
      this review is dedicated to the corrosion of titanium and focuses on possible
      titanium treatments that can increase corrosion resistance. Both surface
      treatments, such as anodization or thermal or chemical oxidation, and bulk
      treatments, such as alloying, are considered, highlighting the advantages of each
      technique.

PMID- 29192719
TI  - Heart disease in chronic kidney disease - review of the mechanisms and the role
      of dialysis access.
AB  - Cardiovascular complications are responsible not only for the high mortality, but
      also the morbidity of end-stage renal disease patients. Cyclic changes of fluid
      load, together with the altered metabolism, are responsible and are mirrored in
      many particular parts of the heart. A review of the mechanisms involved is
      presented and the role of dialysis access is highlighted.

PMID- 29192720
TI  - Resolution of reactive angioendotheliomatosis in an arteriovenous fistula with
      innominate vein angioplasty.
AB  - INTRODUCTION: Arteriovenous fistulae (AVF)-associated reactive
      angioendotheliomatosis (RAE) is a very rare entity (three previously reported
      cases in the literature) that can manifest as extremity wounds. RAE's
      etiopathology is unknown. CASE DESCRIPTION: We report a case of severe limb
      threatening upper extremity wound with pathology-proven RAE. This lesion was
      previously refractory to standard wound care. There was no evidence of limb
      ischemia or steal syndrome, previously deemed to be the underlying cause of AVF
      associated RAE in other reports. CONCLUSIONS: Successful endovascular treatment
      of an ipsilateral innominate vein stenosis led to reduction of venous
      hypertension, resolution of associated arm edema, and subsequent wound healing.
      We therefore propose that venous engorgement and hypertension from central venous
      stenosis is the likely underlying cause for AVF-associated RAE. If this rare
      entity is encountered in the setting of AVF, there is utility in treating the
      wound as a sentinel lesion and venography should be conducted to rule out central
      venous pathology. Vascular intervention complements aggressive local wound
      management and biopsy is requisite for prompt diagnosis.

PMID- 29192721
TI  - Haemodialysis vascular access: current practices amongst Indian nephrologists.
AB  - INTRODUCTION: Despite the growing number of haemodialysis (HD) patients in India,
      little is known about vascular access practice. We investigated the use and cost
      of different vascular accesses by Indian nephrologists. METHODS: An online survey
      was emailed to 920 Indian nephrologists and 388 (42.1%) responded; 98.5% of whom
      were responsible for managing dialysis patients, 98% in hospitals. RESULTS: Sixty
      four percent of patients initiated renal replacement therapy with HD, 7% with
      peritoneal dialysis, 10% kidney transplantation and 19% conservative care. Forty
      eight percent of patients were self-paying, 26% had employee reimbursement and
      23% had insurance. According to 59% of responders, more than three-quarters of
      patients started dialysis with uncuffed catheter, less than one-quarter started
      dialysis with fistula; and very few used grafts or tunnelled catheters. Among
      prevalent HD patients, over half were dialysing with fistula (79% nephrologists),
      rather than uncuffed catheters (15% nephrologists) or grafts (<1% nephrologists).
      Sixteen percent reported at least one catheter-related sepsis in more than half
      of patients. Placement of uncuffed catheters cost US$160 in 92% facilities,
      whereas tunnelled catheters cost US$320 in 46% of facilities. An arteriovenous
      fistula (AVF) could be created for US$160 in 40%, and US$320 in 90% of centres.
      Thirty-five percent of nephrologists reported that grafts were not placed at
      their institute and where they were available, the average cost was over US$480.
      Forty-six percent of nephrologists had access to pre-dialysis clinics, <30% to
      vascular access programmes, and <17% conducted regular vascular access audits.
      CONCLUSIONS: The survey provides a snapshot of the current status of vascular
      access care in HD patients and highlights need for pre-dialysis clinics, vascular
      access services and registry audits.

PMID- 29192722
TI  - Cephalic vein transposition is a durable approach to managing cephalic arch
      stenosis.
AB  - INTRODUCTION: The proximal cephalic vein that enters the axillary vein (cephalic
      arch) is a common site of stenosis in patients with upper extremity arteriovenous
      fistulas for hemodialysis (HD). In this study, we present the outcomes of a
      series of cephalic vein transposition, to determine its utility in the setting of
      refractory arch stenosis. METHODS: We conducted a retrospective review of
      patients undergoing cephalic vein transposition to manage refractory cephalic
      arch stenosis from January 1, 2008 to August 31, 2015. Demographics, past medical
      history, access history of the patients as well as procedural details of the
      surgery to the stenotic segment, patency of the access, and the need for
      subsequent interventions were recorded. RESULTS: Twenty-three patients underwent
      a cephalic vein transposition during the study period. The patients undergoing
      cephalic transposition had their current access for an average of 3.0 +/- 2.6
      years and had an average of 2.3 +/- 0.9 interventions on the access prior to the
      surgery. Complications from the surgery were uncommon (8.7%) and no patient
      required a temporary tunneled dialysis catheter. The re-intervention rate was 0.2
      +/- 0.2 interventions per patient per year. At two years, primary patency was
      70.9% and cumulative patency was 94.7% for the patients with cephalic
      transposition. CONCLUSIONS: Cephalic vein transposition is safe and effective
      treatment for cephalic arch stenosis without interrupting utilization of the
      access. The surgical approach to stenosis of the proximal cephalic vein is
      effective, requires minimal re-interventions, and should be considered for
      isolated, refractory cephalic arch stenosis in mature arteriovenous fistulas.

PMID- 29192724
TI  - Rescue of a subclavian-subclavian arteriovenous "necklace" graft by a HeRO(r)
      catheter.

PMID- 29192723
TI  - Radiation suppresses neointimal hyperplasia through affecting proliferation and
      apoptosis of vascular smooth muscle cells.
AB  - PURPOSE: To study the effect of x-ray radiotherapy on vascular smooth muscle
      cells (VSMCs) and elucidate the mechanisms in preventing neointimal hyperplasia
      of prosthetic vascular grafts. MATERIALS AND METHODS: In model I, twelve mongrel
      dogs underwent revascularization with prosthetic grafts and half the dogs
      underwent irradiation of the grafts at 28 Gy. In model II, human VSMCs (hVSMCs)
      were maintained and divided into six groups to which external radiation was
      applied at six different doses: 0 Gy, 2 Gy, 8 Gy, 16 Gy, 24 Gy and 30 Gy. In both
      models, specimens were harvested and examined by using morphological,
      immunological, cellular and molecular methods. RESULTS: After irradiation, the
      neointima thickness was significantly lower in irradiated groups (p<=0.01). The
      radiotherapy could up-regulate p27kip1, and down-regulate proliferating cell
      nuclear antigen (PCNA) and S phase kinase associated protein 2 (Skp2). X-ray
      irradiation inhibits the proliferation of hVSMCs via acting on G1/S phase of cell
      cycle. The apoptosis of hVSMCs increased significantly with dose and time. The
      expression of PCNA and Skp2 were decreased after a first increasing trend with
      dose, but had a significant negative correlation with time. The expression of
      p27kip1 had a significant positive correlation with dose and time. CONCLUSIONS:
      Postoperative external fractionated irradiation after prosthetic vessel
      replacement of the abdominal aorta suppressed the development of hyperplasia in
      the graft neointima in the short term. There was a prominent time- and dose
      dependent inhibition of VSMC proliferation by radiation when it was administered.

PMID- 29192725
TI  - Viabahn stent for hemodialysis shunt: efficacy, long segment recanalization and
      prognostic factors for reintervention.
AB  - INTRODUCTION: The study evaluated the Heparin Bioactive Surface (HBS) Viabahn
      Stent (W.L. Gore & Associates, Flagstaff, Arizona) efficacy in the maintenance or
      re-establishment of hemodialysis. MATERIALS AND METHODS: Fifty HBS Viabahn stents
      deployed in 37 consecutive patients with hemodialysis dysfunction from January
      2008 to May 2016 were evaluated in a single-institution retrospective review.
      Outcomes were stent patency intended as primary circuit patency (PP), assisted
      primary patency (APP), target lesion primary patency (TLPP) and secondary patency
      (SP). Moreover, the risk factor analysis for hemodialysis dysfunction that
      required reintervention was performed. A subgroup analysis was conducted to
      assess patency of Viabahn stent to treat peripheral venous long segment
      obstruction (LSO). RESULTS: Overall Kaplan-Meyer PPs were 60% at 12 months and
      42% at 24 months. Overall TLPP estimated rates were 68% and 49% at 12 and 24
      months, respectively. The corresponding SP rates were 85% and 78% at the same
      period. Estimated PP rates at 12 and 24 months for stent placement after
      peripheral venous long segment recanalization procedure were 53% and 31%,
      respectively. Corresponding SP rates were 82% and 68%, respectively. The APP
      rates were 79% at 12 months and 61% at 24 months. Female sex, access age and
      thrombosis were associated with reduced primary patency. CONCLUSIONS: Considering
      the high rates of PP, TLPP, APP and SP, Viabahn stents have been proven effective
      in maintaining or re-establishing the hemodialysis access. Moreover, stent
      placement after recanalization of LSO of venous out-flow represented a valid
      approach to rescue a dysfunctional fistula that would otherwise be abandoned.

PMID- 29192726
TI  - Outcomes in patients with late sequelae (healed stage) of Legg-Calve-Perthes
      disease undergoing arthroscopic treatment: retrospective case series.
AB  - INTRODUCTION: The residual hip deformities after Legg-Calve-Perthes disease
      (LCPD) cause mechanical symptoms and are associated with a pathomechanical
      environment that can feature femoroacetabular impingement (FAI). The aim of this
      study is to evaluate the clinical and radiological outcomes in residual or healed
      LCPD after arthroscopic treatment. PATIENTS AND METHODS: We retrospectively
      reviewed patients with LCPD amongst patients with FAI who underwent arthroscopic
      treatment between January 2009 and June 2013. We determined LCPD through 3
      dimensional computed tomographic scans and simple radiography of the hip joint.
      The clinical outcomes were rated using a visual analogue scale pain score (VAS),
      the modified Harris Hip Score (mHHS) and hip range of motion (ROM) preoperatively
      and at the 2-year follow-up. All radiographs were assessed using the Tonnis
      classification system preoperatively and at the final follow-up of each patient.
      There were 23 patients (14 men, 9 women) with mean age 26.4 (range, 16-49) years
      undergoing arthroscopic treatment for FAI symptoms because of residual or healed
      LCPD. RESULTS: At the 2-year follow-up, the mean VAS had improved significantly
      from 6.7 to 2.1, the mean mHHS had improved significantly from 62.6 to 87.4, and
      hip flexion and external rotation had improved significantly from 88.7 degrees 
      to 106.5 degrees  and from 20.4 degrees  to 33.5 degrees , respectively (all
      p<0.001). The Tonnis osteoarthritis grade had not changed in any patient at the
      latest follow-up. CONCLUSIONS: Arthroscopic treatment for sequelae of LCPD
      relieved symptoms and improved range of motion, making arthroscopic treatment a
      good option for the sequelae of LCPD.

PMID- 29192727
TI  - Which is the best bearing surface for primary total hip replacement? A New
      Zealand Joint Registry study.
AB  - INTRODUCTION: We have investigated the revision rates of all bearing surface
      combinations for primary total hip replacement (THR) registered on the New
      Zealand Joint Registry (NZJR) to determine which coupling has been the most
      durable and successful over the last 16 years. METHODS: There were 106,139
      primary THRs registered, resulting in 4,960 revisions for any cause. We examined
      all-cause revision rates, reasons for revision and performed survival analyses.
      RESULTS: Ceramic-on-highly cross-linked polyethylene (CoPx) had the lowest all
      cause revision rate of 0.54/100-component-years (cys) (95% confidence interval
      0.48 to 0.61). This was superior to all other hard-on-soft bearing combinations
      in unadjusted analysis. Furthermore, the age of patients receiving CoPx was
      significantly lower than for metal-on-polyethylene (mean 62.9; standard deviation
      [SD] 10.1 vs. 69.1; SD 9.6; p<0.001). Acetabular loosening was the reason for
      revision in 14.5% of CoPx, compared to 33% of MoP THRs (p<0.001). Metal-on-metal
      bearings had the highest revision rate of 1.43/100 cys and were significantly
      inferior to CoPx (p<0.001). Kaplan-Meier analysis and Cox regression analyses
      were performed and we adjusted the analyses to control for age, femoral head
      size, surgical approach and fixation. CONCLUSIONS: CoPx remained the most durable
      and successful coupling used in primary THR in New Zealand irrespective of age,
      gender or size of femoral head.

PMID- 29192728
TI  - Overestimation of the risk of revision with Kaplan-Meier presenting the long-term
      outcome of total hip replacement in older patients.
AB  - INTRODUCTION: The purpose of the present study was (i) to review the long-term
      outcome of cemented Charnley total hip replacements (THRs) performed by 1 surgeon
      (GH), 20 to 42 years ago, in patients >=60 years, using both the Kaplan-Meier
      (KM) and the cumulative incidence (CI) methods, and (ii) to compare the
      estimations of the 2 statistical methods. METHODS: We evaluated the outcome of
      306 consecutive primary cemented THRs that were performed in 265 patients. The
      final clinical, radiographic assessment and satisfaction of living patients were
      also included. The survivorship was estimated with the use of KM and CI methods
      and the relative difference between their estimations was calculated. RESULTS:
      Living patients' final clinical results were significantly improved in comparison
      with respective preoperative ones, and all the acetabular and 91% of femoral
      components considered as well fixed. 95% of these patients reported satisfaction.
      The risk of revision at 25 years, with revision for aseptic loosening for 1 or
      both components as the endpoint, with 21 hips at risk, assessed with KM analysis
      was 6.9% and with CI approach was 3.9%. The relative difference between KM and CI
      estimations was increasing during follow-up, reaching up to 76.8% at 25 years.
      CONCLUSIONS: We concluded that fixation of implants with cement in older patients
      had satisfactory long-term results and can serve as a benchmark with which to
      compare newer fixation methods (hybrid and uncemented) and materials. However, KM
      method, in studies that include older population with long-term follow-up, may
      significantly overestimate the risk of revision and clinicians could consider
      using besides the cumulative incidence of competing risk method.

PMID- 29192729
TI  - Experience and outcome data of the British non-arthroplasty hip registry.
AB  - INTRODUCTION: The non-arthroplasty hip registry (NAHR) is a United Kingdom
      national register that monitors the efficacy of hip preservation surgery. We aim
      to highlight early experiences of incorporating the NAHR into our practice at a
      tertiary centre. METHODS: Between December 2013 and February 2015, 381 patients
      were identified on the NAHR database that had undergone non-arthroplasty hip
      surgery. Patient-related outcome measures EuroQuol 5D-5L (EQ-5D) and the
      International Hip Outcome Tool 12 (iHOT-12) were recorded at baseline and 6
      months. RESULTS: The 289 arthroscopic surgeries showed a statistical significant
      difference (p<0.05) in iHOT-12 for both males (45.21-65.07) and females (34.57 to
      55.53), and in EQ-5D for both males (0.59-0.75) and females (0.56-0.65). The 92
      open procedures showed a statistical significant difference (p<0.05) in both iHOT
      12 (31.71-62.42) and EQ-5D (0.54-0.68). CONCLUSIONS: Overall our results from the
      NAHR indicate hip preservation surgery is effective at relieving pain and
      improving quality of life in the short term.

PMID- 29192730
TI  - 3-phase Technicium-99m bone scanning in patients with pain in the hip region
      after cemented total hip replacement: a multicentre series of 100 cases.
AB  - INTRODUCTION: The aim of this study was to assess the benefit of a Technetium-99M
      (HDP) 3-phase bone scan (TPBS) as an additional diagnostic test in the evaluation
      of pain in the hip region following cemented total hip replacement (THR) surgery.
      METHODS: A retrospective study over a 24-month period was performed comprising
      100 patients investigated with a TPBS. Investigations were summarised and
      analysed, and were classified as entirely normal, possibly abnormal, and
      definitely abnormal. RESULTS: 45% (45) of TPBSs were reported as being entirely
      normal, 50% (50) as possibly abnormal, and 5% (5) as definitely abnormal. During
      the 24-month study period 230 revision THR procedures were performed at our
      institution; 10% (24) were investigated with TPBS and 90% (206) were not. 29%
      (7/24) of patients investigated with a TPBS that subsequently underwent revision
      THR surgery had an entirely normal preoperative TPBS. 84% (38) with an abnormal
      TPBS were managed conservatively. A TPBS had a sensitivity of 29% (95% confidence
      interval (CI), 13%-51%) and a specificity of 50% (95% CI, 38%-62%) in the
      detection of infection, or loosening with concurrent infection. CONCLUSION: A
      TPBS should only be considered following clinical evaluation, serological
      investigation, diagnostic imaging and microbiological analysis of fluid obtained
      from arthrocentesis by a specialist revision arthroplasty surgeon. A TPBS may be
      useful in the situation where abnormal serology is present, but where repeated
      joint aspirations samples are inconclusive.

PMID- 29192731
TI  - Up to 10-year follow-up of the Symax stem in THA: a Danish single-centre study.
AB  - INTRODUCTION: The design of the cementless Symax-HA femoral stem is based on
      geometrical analysis of human femoral anatomy to optimise the fit within the
      femur. The stem combines an anatomical proximal section enabling a metaphyseal
      anchorage with a straight distal section. This results in an improved proximal
      load transfer. We aimed to determine the overall survival of total hip
      arthroplasty (THA) in patients operated at our institution with the Symax stem.
      Secondly, we investigated the cause of revision for patients having THA including
      the Symax stem. METHODS: The study is a registry study with results from a single
      centre, Vejle Hospital. From the Danish Hip -Arthroplasty Registry, we identified
      all THAs operated with the Symax stem. The primary outcome was revision. The
      secondary outcomes were aseptic loosening, periprosthetic fracture, and all other
      causes for revision. RESULTS: In total, 1,055 THAs were performed in 875
      patients. The median 6.5-year survival rate was 97.5% (95% confidence interval
      [CI]: 96.6%-98.3%). 29 THAs had undergone revision due to the following causes:
      periprosthetic fracture (n = 11); aseptic loosening of the cup (n = 1); infection
      (n = 5); dislocation (n = 10); and component failure (n = 2). There was no
      revision due to aseptic loosening of the stem. CONCLUSIONS: From the Danish Hip
      Arthroplasty Registry, we identified the overall 6.5-year survival rate to be 95%
      for cementless THAs. In the present study, the Symax stem has a median 6.5-year
      survival rate at 97.5% (96.6%-98.3%). No revisions were due to aseptic loosening
      but the stem had a relative high prevalence of periprosthetic fractures.

PMID- 29192732
TI  - Leg length discrepancy after total hip arthroplasty: comparison of 3
      intraoperative measurement methods.
AB  - INTRODUCTION: Total hip arthroplasty (THA) is 1 of the most successful and
      frequent orthopaedic procedures around the world. Leg length discrepancy is
      reported in 1% to 60% of cases and is 1 of the most frequent causes of patient
      dissatisfaction and a common reason for litigation. The aim of this study was to
      compare leg length discrepancies following THA using 3 different intraoperative
      measuring methods. MATERIAL AND METHODS: We present a prospective cohort study of
      454 hips undergoing THA for osteoarthritis between January 2009 and August 2016.
      We compared postoperative leg length discrepancy using 1 of the following 3
      measurement methods: (1A) direct intraoperative comparison of the legs; (1B)
      measurement with a compass-like device with supra-acetabular fixation, involving
      length and offset; (1C, D) an intraoperative device that measures the
      trochanteric/joint ratio. RESULTS: Leg length discrepancy >5 mm was present in
      26% of the total study population. Direct intraoperative leg-to-leg assessment
      resulted in the greatest proportion of leg length discrepancy >5 mm (31%),
      followed by the compass group (27%) and the least discrepancy was observed in the
      trochanteric/joint ratio group (15%). The trochanteric/joint ratio assessment
      method resulted in the greatest reduction in discrepancy when compared to the
      other methods: discrepancies of 5-10 mm fell by 48% (relative risk [RR] 0.40 CI
      [confidence interval [CI] 95%, 0.22-0.74), and discrepancies of >=10 mm fell by
      59% (RR 0.52; CI 95%, 0.32-0.84). CONCLUSIONS: We conclude that the use of an
      intraoperative measurement device can reduce the leg length discrepancy, with
      best results when using the trochanteric/joint ratio device.

PMID- 29192733
TI  - Systematic review: lack of evidence for the success of revision arthroplasty
      outcome in younger patients.
AB  - INTRODUCTION: Total hip arthroplasties (THAs) in younger patients are becoming
      increasingly popular. However, the outcome of subsequent revisions in younger
      patients is not well known and, therefore, their success (subsequent revision
      prosthesis survival) might be overestimated. We investigated available data on
      the outcome of primary- and subsequent revision THAs performed in the same cohort
      of patients who underwent primary THA under the age of 50. METHODS: Medline,
      Embase and the Cochrane Library (CENTRAL) were searched up until April 13, 2016
      for studies that reported both the survival of primary and subsequent revisions
      THA of single cohorts of patients younger than 50. Eligible articles had to
      include Kaplan Meier analysis or competing risk analysis for survival of the
      primary THA at a mean follow-up of 10 years, as well as for the subsequent
      revision THA within the same cohort. RESULTS: We found 4,799 unique records; 43
      of which were potentially eligible. Only 1 paper met our inclusion criteria. It
      reported on the survival of 69 primary prostheses at a mean of more than 10 years
      follow-up and 13 subsequent revisions. CONCLUSIONS: There is a clear lack of
      evidence about the outcomes of the revision arthroplasty in younger patients.
      Only 1 study reported the survival-rate of subsequent revision arthroplasty with
      the minimum 10-year survival rate of the original THA cohort. In the future, this
      serious lack of knowledge could result in a large number of patients with no
      further reconstructive options after failed THA, and a large medical burden for
      society.

PMID- 29192734
TI  - Wear rate and medium-term survival of a cemented, moderately cross-linked
      polyethylene acetabular prosthesis.
AB  - INTRODUCTION: The moderately cross-linked Depuy Marathon(r) cemented acetabular
      component was introduced into the UK in 2007. The wear rate for the previously
      introduced Marathon(r) uncemented acetabular component has been reported to range
      from 0.06 to 0.01 mm/year. The aim of this study was to present the medium-term
      results and wear rate of the Marathon(r) cemented prosthesis used in primary
      total hip arthroplasty. METHODS: 103 Marathon(r) cemented acetabular components
      were implanted between 2008 and 2009 in primary arthroplasty, who were eligible
      for this study. All patients received a metal 28-mm head. Mean age was 68 years
      (range 27-87). Mean clinical follow-up was 55 months (range 50-61). Mean
      radiological follow-up was 46 months (range 24-57). Wear was calculated on AP
      radiographs using computer-assisted uni-radiographic technique. RESULTS: The mean
      wear was 0.37 mm (range 0.0-0.78 mm). The wear rate was calculated as 0.03
      mm/year (95% confidence interval 0.02-0.06). Postoperative complications included
      deep vein thrombosis (2%) and dislocation (0.8%); there were no deep infections.
      There were no revisions for failure of the Marathon(r) cemented acetabular
      component. CONCLUSIONS: The Marathon(r) cemented acetabular component
      demonstrates satisfactory wear rates and survivorship at medium-term follow-up.

PMID- 29192735
TI  - Total hip arthroplasty in younger patients: are there other options in China?

PMID- 29192736
TI  - Operative findings and complications associated with adjunctive hip arthroscopy
      in 95 hips undergoing periacetabular osteotomy.
AB  - PURPOSE: to report our initial experience with adjunctive hip arthroscopy and
      periacetabular osteotomy (PAO). METHODS: Retrospective review of patients who
      underwent PAO and ipsilateral hip arthroscopy between 2003 and 2013. Indications
      for arthroscopy were mechanical symptoms and/or positive magnetic resonance
      imaging to suggest intra-articular pathology including chondrolabral lesions,
      ligamentum teres tears and hypertrophy, and synovitis. Preoperative Tonnis
      arthritis grades, age, sex, operative findings and treatment, complications, and,
      if available, hip survival were recorded. RESULTS: Of 78 patients (95 hips)
      included, 64 (82%) were female and 14 (18%) male, average age was 30.6 (14-63)
      years. Tonnis grades were 0 in 40 hips (42%), 1 in 45 hips (47%), and 2 in 10
      hips (11%). No Tonnis 3 hips were included. 84% of hips demonstrated labral
      pathology. 92% had chondromalacia, which was severe enough in 4 patients to
      warrant cancellation of PAO; all 4 have subsequently required total hip
      replacement at short-term follow-up. Labral debridement was performed in 73 hips
      and refixation in 7. 5 postoperative complications occurred - none major,
      including 1 fluid extravasation, 1 case of heterotopic ossification, and 3
      transient neuropraxias. CONCLUSIONS: Intraarticular pathology is highly prevalent
      in patients undergoing PAO with mechanical symptoms, and can be safely managed by
      adjunctive arthroscopy. Complications were minimal in our series and are
      comparable to reports of PAO without arthroscopy. Arthroscopy can treat pathology
      that is inaccessible during standalone PAO and permits avoidance of routine
      arthrotomy, surgical dislocation, rectus release, and futile PAO in cases with
      severe articular damage.

PMID- 29192737
TI  - Dreams and Illusions in Adolescents with Terminal Cancer.
AB  - Being diagnosed with cancer in adolescence generally has important emotional
      consequences: adolescent cancer patients need to be seen as special cases with
      particular medical and psychosocial needs. This is especially true when a young
      patient is faced with a progressive, incurable disease. Herein, we report the
      story of a 17-year-old girl with a metastatic refractory soft tissue sarcoma who
      tells her dream to the psychologist of the ward. Telling this narrative is the
      opportunity to discuss the complex topic of how adolescent cancer patients adapt
      to the terminal stage of their disease; for example, the patient needs to talk to
      someone about their fear of dying; the healthcare operators need to be able
      properly listen and communicate; the patient's trust in the future despite their
      clinical condition; the necessity to leave space for hope; the useful role of the
      imagination sphere; the issue of whether and how to tell a person who is
      terminally ill the truth about their condition.

PMID- 29192738
TI  - Role of perioperative dynamic sentinel node biopsy for cN0 penile cancer
      management: experience from an Italian tertiary referral center.
AB  - PURPOSE: Inguinal lymphadenectomy (iLAD) reduces mortality in patients with cN0
      penile cancer but yields high complication rates. Thus, its prophylactic role has
      been questioned and dynamic sentinel node biopsy (DSNB) was introduced to select
      men who should undergo the procedure. Our aim was to investigate the accuracy of
      a contemporary DSNB cohort. METHODS: We performed a retrospective analysis of
      >=T1 or >=G2 cN0 penile cancer undergoing perioperative DSNB from June 2009 to
      June 2015 at a tertiary referral center. We excluded men with <18 months follow
      up or with local recurrence after primary curative treatment. Complications were
      graded according to the Clavien-Dindo classification. RESULTS: Thirty-five men
      underwent DSNB; 85.71% had <=T2 penile cancer with <=G2a histology. Per groin
      detection rate was 80% (scintigraphy being positive bilaterally in 60% and
      unilaterally in 20.0%). In no cases did DSNB prolong the postoperative course
      compared to primary surgery. Nine men (n = 15/109 nodes removed) had positive
      results, 8 of whom underwent iLAD. Among negative DSNB patients, 2 developed
      nodal penile cancer recurrence; none of them had node biopsy due to inconclusive
      scintigraphy. At a median follow-up of 42 months (interquartile range 30-78
      months), if considering only men with scintigraphy detected inguinal nodes, per
      patient sensitivity and specificity were 50% and 80% whereas positive predictive
      value and negative predictive value were 25% and 92.3%, respectively.
      CONCLUSIONS: Perioperative DSNB is a safe procedure, yielding promising results
      when performed at a tertiary referral center. Future prospective large studies
      are needed to investigate how to optimize detection rate and reduce false
      negative rates.

PMID- 29192739
TI  - Risk prediction model for disease-free survival in women with early-stage
      cervical cancers following postoperative (chemo)radiotherapy.
AB  - PURPOSE: To investigate disease-free survival (DFS) and prognostic factors
      following the administration of postoperative (chemo)radiotherapy in patients
      with early-stage cervical cancers. METHODS: The medical records of 1,069 patients
      from 10 participating institutions were reviewed. Statistically and clinically
      established factors were considered as candidates for constructing the prediction
      model. This model was validated, using bootstrapping to correct for optimistic
      bias. RESULTS: The 5-year DFS rate was 81.1%, with a median follow-up period of
      59.6 months. The statistically significant prognostic factors were as follows:
      pelvic lymph node metastasis, histologic type, parametrial invasion,
      lymphovascular space invasion, and tumor size. The nomogram for DFS was
      constructed, and it demonstrated a good discrimination performance, with an
      internally validated concordance index of 0.72. CONCLUSIONS: Our predictive model
      exhibited accurate predictions and may be useful in designing clinical trials to
      study if further chemotherapy can reduce the recurrence of disease in high-risk
      patients.

PMID- 29192740
TI  - Bilateral Parotid Gland Metastases from Gastric Signet-Ring Cell Carcinoma.
AB  - Introduction Signet-ring cell (SRC) carcinoma is a common subtype of gastric
      adenocarcinoma associated with poor prognosis. Metastatic involvement of the
      parotid gland has been reported in gastric cancer patients, but never bilaterally
      nor in association with the SRC histotype. Here, we report the first case and a
      brief review of the literature. Case description A 47-year-old woman was referred
      to our center for a signet-ring gastric carcinoma with synchronous hepatic and
      peritoneal metastases. After 3 lines of chemotherapy, the patient reported a
      progressive bilateral enlargement in the periauricolar area. An ultrasound of the
      salivary glands and a fine needle biopsy were diagnostic for parotid metastases
      of gastric origin. In the literature, only 3 cases of parotid gland metastases
      arising from gastric cancer are described - none with a feature of SRC carcinoma.
      Conclusions To the best of our knowledge, this is the first report of gastric SRC
      carcinoma with bilateral parotid metastases. This case highlights the importance
      of considering a parotid enlargement as a possible sign of disease progression in
      a patient with gastric cancer. Fine-needle biopsy and immunocytochemistry are
      essential in establishing the origin of the secondary lesion.

PMID- 29192741
TI  - TARIBO trial: targeted therapy with or without nephrectomy in metastatic renal
      cell carcinoma: liquid biopsy for biomarkers discovery.
AB  - PURPOSE:: Two randomized trials in the cytokine era showed that cytoreductive
      nephrectomy (CN) had a role in metastatic renal cell carcinoma (mRCC), increasing
      life expectancy. The survival benefit of tyrosine kinase inhibitors (TKIs),
      including first-line sunitinib and pazopanib, in mRCC has been demonstrated, but
      the majority of patients enrolled in the pivotal phase III studies had undergone
      nephrectomy. Therefore it is unknown if similar survival benefit with targeted
      agents could be achieved without CN. We hypothesize that in these patients CN
      could increase overall survival (OS) in comparison to targeted therapy without
      CN. We also will investigate mechanisms of primary and secondary resistance to
      TKIs in patients with mRCC and identify prognostic or predictive biomarkers.
      METHODS:: This is a randomized, open-label, controlled, multicenter phase 3 study
      comparing sunitinib or pazopanib vs CN followed by sunitinib or pazopanib as
      first-line therapy for patients with mRCC who have not received surgery and prior
      systemic treatment for metastatic disease. We will identify 270 patients eligible
      for randomization. The planned treatment duration per patient will be until
      progressive disease is observed. Secondary endpoints are the evaluation of
      progression-free survival (PFS) and response rate and the assessment of the
      safety profile. Exploratory objectives include the evaluation of circulating
      tumor cells and circulating tumor DNA and correlation with response/resistance to
      treatment. RESULTS:: The study is enrolling patients. CONCLUSIONS:: The use of CN
      in addition to targeted therapy in patients with renal cell carcinoma with
      synchronous metastases could lead to a significant improvement in OS and PFS.

PMID- 29192742
TI  - Biliary tract rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee
      of the Associazione Italiana Ematologia Oncologia Pediatrica.
AB  - INTRODUCTION: Rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor
      frequent in children. Biliary duct localization is extremely rare, but it is the
      most common cause of malignant obstructive jaundice in pediatric patients.
      METHODS: This report describes a series of 10 patients under 18 years of age with
      biliary tract rhabdomyosarcoma who were enrolled, from 1979 to 2004, in 3
      consecutive Italian pediatric cooperative protocols that had been drawn up by the
      Soft Tissue Sarcoma Committee of the Associazione Italiana Ematologia Oncologia
      Pediatrica (AIEOP). RESULTS: Considering initial and delayed surgery, tumor
      resection was achieved in 7 cases, 3 complete with free margins (2 liver
      transplants) and 4 with microscopic residual disease. Chemotherapy was given to
      all patients and radiotherapy to 3. At present, 5 patients survive in complete
      remission 90-200 months after diagnosis while 4 died of disease progression or
      relapse and 1 of liver transplant-related complications. CONCLUSIONS: Better
      outcomes in this series were associated with the feasibility of conservative
      surgery due to the favorable location of the tumor, in particular in the common
      bile duct. Chemotherapy and radiotherapy might obviate the need for demolitive
      surgery or liver transplant, which were linked to worse outcomes in our series.

PMID- 29192743
TI  - Can pancreatic cancer be detected by adrenomedullin in patients with new-onset
      diabetes? The PaCANOD cohort study protocol.
AB  - INTRODUCTION: Pancreatic cancer is a leading cause of cancer-related death. Its
      diagnosis is often delayed and patients are frequently found to have unresectable
      disease. Patients diagnosed with new-onset diabetes have an 8-fold risk of
      harboring pancreatic cancer. Adrenomedullin has been claimed to mediate diabetes
      in pancreatic cancer. New screening tools are needed to develop an early
      diagnosis protocol. METHODS: Patients aged 45-75 years within 2 years of first
      fulfilling the ADA criteria for diabetes will be prospectively enrolled in this
      study. Sepsis, renal failure, microangiopathy, pregnancy, acute heart failure and
      previous malignancies will be considered as exclusion criteria. RESULTS: 440
      patients diagnosed with new-onset diabetes will be enrolled and divided into 2
      groups: one with high adrenomedullin levels and one with low adrenomedullin
      levels. Patients will undergo 3 years' follow-up to detect pancreatic cancer
      development. CONCLUSIONS: Identifying a marker for pancreatic cancer among high
      risk patients such as new-onset diabetics might lead to the identification of a
      subpopulation needing to be screened in order to enable early diagnosis and
      treatment of a highly lethal tumor. TRIAL REGISTRATION: This trial was registered
      at ClinicalTrials.gov on May 25, 2015 under registration number NCT02456051.

PMID- 29192744
TI  - Thirty-day mortality and five-year survival in thoracic surgery: "real-world"
      assessment of outcomes from a single-institution audit.
AB  - BACKGROUND: Accurate measurement of outcomes is essential to monitor the
      effectiveness of public health policies. In Italy, the Ministry of Health has
      chosen 30-day mortality after major surgical or medical procedures as the main
      outcome measure, pooling all pulmonary resections for malignancy in a single
      category. The present audit evaluated all pulmonary resections performed over a
      13-year period in a single institution to assess the immediate (30-day mortality)
      and long-term (5-year survival) outcomes according to type and stage of disease
      and extent of surgery. METHODS: We analyzed the results of 4,234 first pulmonary
      resections performed from 2003 to 2015 for lung cancer (2,636), lung metastases
      (1,080), other primary cancers (259) and benign diseases (259). The median follow
      up of cancer patients was 4.1 years. RESULTS: Overall 30-day mortality was 1.1%,
      being 1.2% for lung cancer, 0.3% for lung metastases, 3.5% for pneumonectomies,
      1% for lobectomies, and 0.5% for sublobar resections. Among lung cancer patients,
      30-day mortality was 0.7% for simple anatomical resections, 2.8% for complex
      resections, 0.7% for stage I, and 1.6% for higher stages. Overall 5-year survival
      was 56% for lung cancer, 49% for lung metastases, and 53% for other primary
      cancers (p = 0.03). According to the surgical procedure for lung cancer, 5-year
      survival was 60%, 55% and 36% for lobectomies, segmentectomies and
      pneumonectomies, respectively (p<0.0001). CONCLUSIONS: For better monitoring of
      thoracic surgery outcomes in a real-world setting, we suggest evaluating lung
      cancer separately from other thoracic malignancies, and including 5-year survival
      rates stratified by resection volume and surgical procedure complexity.

PMID- 29192746
TI  - Zika virus outbreak: reproductive effects and decreases in the number of births
      in Brazil.

PMID- 29192745
TI  - Impact of coexistent adenomyosis on outcomes of patients with endometrioid
      endometrial cancer: a propensity score-matched analysis.
AB  - PURPOSE: Despite the common occurrence of adenomyosis in endometrial cancer (EC),
      there is a paucity and conflict in the literature regarding its impact on
      outcomes of patients. We sought to compare outcomes of patients with endometrioid
      type EC with or without adenomyosis. METHODS: A total of 314 patients were
      included in the analysis. Patients were divided into 2 groups according to the
      presence or absence of adenomyosis. Adenomyosis was identified in 79 patients
      (25.1%). A propensity score-matched comparison (1:1) was carried out to minimize
      selection biases. The propensity score was developed through multivariable
      logistic regression model including age, stage, and tumor grade as covariates.
      After performing propensity score matching, 70 patients from each group were
      successfully matched. Primary outcome of the study was disease-free survival
      (DFS), and the secondary outcomes were overall survival (OS) and disease-specific
      survival (DSS). RESULTS: Median follow-up time was 61 months for the adenomyosis
      positive group and 76 months for the adenomyosis negative group. There were no
      statistically significant differences in 3- and 5-year DFS, OS, and DSS rates
      between the 2 groups. Five-year DFS was 92% vs 88% (hazard ratio [HR] 1.54 [0.56
      4.27]; p = 0.404), 5-year OS was 94% vs 92% (HR 1.60 [0.49-5.26]; p = 0.441), and
      5-year DSS was 94% vs 96% (HR 2.51 [0.46-13.71]; p = 0.290) for patients with and
      without adenomyosis, respectively. CONCLUSIONS: Coexistent adenomyosis in EC is
      not a prognostic factor and does not impact survival outcomes.

PMID- 29192747
TI  - [Situational diagnosis of cancer care at the Instituto Mexicano del Seguro
      Social].
AB  - Cancer is a public health problem with an impact on Health Services in Mexico; it
      is also, one of the leading causes of mortality (mortality rate: 610.6 / 100 000)
      and is expected to double the total number of new cases by 2035 (GLOBOCAN). The
      most frequent neoplasms are the malignant tumor of breast, prostate, cervix and
      uterin, colorectal and pulmonary. The most affected groups are the female, and by
      age the 65 years and older (INEGI). At the IMSS, the mortality rate for malignant
      tumors has varied, with a sustained decline since 2010. In the last 15 years
      there has been a growth of 15% of the Disability Adjusted Life Years; during
      which the IMSS spent 2% of its current expenditure resources of the Health
      Insurance and Maternity. The IMSS has a network of medical units capable of
      attending to the process of prevention, early detection, diagnosis, treatment and
      rehabilitation of cancer patients. With the commitment of its improvement and to
      fulfill the National Health Programs, the OncoIMSS Program was created, with a
      reorganization of the care process with opportunity, quality, optimization of
      resources, regionalization, strengthening of infrastructure and trained human
      capital.

PMID- 29192748
TI  - A middle aged woman with isolated ACTH deficiency associated with transient
      growth hormone deficiency.
AB  - Isolated ACTH deficiency (IAD) is a rare entity characterized by secondaryadrenal
      insufficiency with low levels of serum cortisol, decreasedproduction of ACTH,
      adequate secretion of other pituitary hormonesand normal pituitary structure on
      radioimaging. The prevalence ofIAD as a cause of secondary adrenal insufficiency
      has not been determined.Impairment of growth hormone (GH) secretion has beennoted
      in 20 to 30% of patients with IAD which is normalized after
      glucocorticoidreplacement. We report the case of a 50 years-old femalewith
      symptoms and laboratory results suggestive of adrenal insufficiency.Insulin
      tolerance test confirmed ACTH and growth hormonedeficiency. The rest of the
      anterior pituitary hormones were normal. Apituitary MRI was unremarkable.
      Glucocorticoid replacement therapystarted and eight months afterwards glucagon
      stimulation test revealedpersistent ACTH deficiency but nor-mal growth hormone
      secretion. IAD can present with nonspecific symptomsand could be potentially
      fatal in an acute stressful period. Promptrecognition is essential to decrease
      morbidity and mortality.

PMID- 29192749
TI  - Adequate Administration of Perioperative Antibiotics in Orthopedic Patients:
      Quality Assessment Study.
AB  - The Centers for Disease Control and Prevention (CDC) estimate thatnearly 500,000
      surgical site infections (SSIs) occur annually.[3] SSIs remaina substantial cause
      of morbidity and mortality among hospitalized patients.For this reason, we
      developed a quality assessment study with aperioperative antibiotic protocol that
      included antibiotic type, weight dependentdose, and intraoperative re-dosing
      regime for the proper administration of prophylaxis antibioticsprior to
      orthopedic surgery. We restricted our study to knee replacementand hip
      replacement surgeries. All records from September 2014 to June2015 were taken
      into consideration (78 cases). Before February 2015(protocol implementation
      date), only 33% or 13 of 39 cases were correctlydosed. After protocol
      establishment: 44 % or 17 of 39 cases were correctlydosed. Although our p-value
      suggests no statistical significance, there wasan increasing trend of adequate
      antibiotic administration. In conclusion,we need to educate more our nursing
      staff and implement monthly auditsof our cases to improve our mistakes and ensure
      that this aspect of practicewill remain in the forefront of perioperative
      orthopedic surgery care.

PMID- 29192750
TI  - Association between fine needle aspiration cytologyand final pathology in the
      diagnosis of thyroid noduleswith surgical indications.
AB  - Fine needle aspiration of thyroid (FNA) is broadly used as the
      preferredpreoperatory test to evaluate thyroid nodules. The clinical importance
      ofthis procedure is primarily related the need to exclude Thyroid Cancer.There
      are few studies investigating the association between FNA and finalpathology in
      patients with thyroid nodules with surgical indications.There is no evidence from
      studies in the southern area of Puerto Rico thatinvestigate this association.
      This was a randomized cross-sectional study, 82medical records were evaluated.
      Data were obtained for FNA diagnosis,demographics, body mass index, findings on
      ultrasound and histopathologyresults. In this study the sensitivity of FNA was
      73.53% and specificity of100%. The accuracy of the study was 78%. The study
      reported a prevalenceof 83% malignant tumors in the final pathology and 61% in
      the FNA. Thepositive predictive value was 100% and negative 43.75%, suggesting
      thatFNA is a good diagnostic test to detect thyroid nodules suspicious
      formalignancy. FNA of 33 patients was reported with undetermined
      cytopathology.The measure of agreement and correlation coefficient showed
      amoderate agreement between both studies with a Kappa value of 0.487,suggesting
      that the test results of FNA and final pathology are associated.Of the
      indeterminate nodules, final pathology reported 15 benign and 18malignant. This
      study demonstrated that the FNA is reliable in identifyingthyroid nodules in
      patients with surgical indications.

PMID- 29192751
TI  - Anion Exchange Membranes: Enhancement by Addition of Unfunctionalized Triptycene
      Poly(Ether Sulfone)s.
AB  - Anion exchange membrane fuel cells are a clean and efficient promising future
      energy source. However, the development of stable high-performance membranes
      remains a major challenge. Herein we demonstrate that the addition of
      unfunctionalized triptycene poly(ether sulfones) into 1-methylimidazolium
      poly(ether sulfone) enhances membrane's conductivity (up to 0.082 S/cm at 80 
      degrees C), minimizes dimensional changes over temperatures from 20 to 80 
      degrees C, and enhances stability with 30% of the initial conductivity maintained
      after 450 h. These enhancements appear to be the result of nanophase separation
      and internal free volume. Small angle X-ray scattering and transmission electron
      microscopy reveal that the internal domain size increases (up to 7.44 nm) with
      increasing triptycene fraction.

PMID- 29192752
TI  - Graphene Oxide-Poly(dimethylsiloxane)-Based Lab-on-a-Chip Platform for Heavy
      Metals Preconcentration and Electrochemical Detection.
AB  - Herein, we present the application of a novel graphene oxide
      poly(dimethylsiloxane) (GO-PDMS) composite in reversible adsorption/desorption,
      including detection of heavy metals. GO-PDMS was fabricated by simple blending of
      GO with silicon monomer in the presence of tetrahydrofuran, followed by
      polymerization initiated upon the addition of curing agent. We found GO
      concentration, curing agent concentration, pH, and contact time among the most
      important factors affecting the adsorption of Pb(II) used as a model heavy metal.
      The mechanism of adsorption is based on surface complexation, where oxygen active
      groups of negative charge can bind with bivalent metal ions Me(II). To
      demonstrate a practical application of this material, we fabricated microfluidic
      lab-on-a-chip platform for heavy-metals preconcentration and detection. This
      device consists of a screen-printed carbon electrode, a PDMS chip, and a GO-PDMS
      chip. The use of GO-PDMS preconcentration platform significantly improves the
      sensitivity of electrochemical detection of heavy metals (an increase of current
      up to 30* was observed), without the need of modifying electrodes or special
      reagents addition. Therefore, samples being so far below the limit of detection
      (0.5 ppb) were successfully detected. This approach is compatible also with real
      samples (seawater) as ionic strength was found as indifferent for the adsorption
      process. To the best of our knowledge, GO-PDMS was used for the first time in
      sensing application. Moreover, due to mechanical resistance and outstanding
      durability, it can be used multiple times unlike other GO-based platforms for
      heavy-metals adsorption.

PMID- 29192753
TI  - Structural Stability of N-Alkyl-Functionalized Titanium Metal-Organic Frameworks
      in Aqueous and Humid Environments.
AB  - We demonstrate that the highly photoredox active metal-organic framework (MOF)
      MIL-125-NHCyp exhibits crystalline and porosity stability in humid environments
      for more than 30 days as well as increased hydrophobicity compared to the
      unfunctionalized framework. This improved stability, in synergy with its high
      photocatalytic activity, makes this MOF a very promising candidate for large
      scale applications in CO2 photoreduction.

PMID- 29192754
TI  - Superior Pseudocapacitive Lithium-Ion Storage in Porous Vanadium Oxides@C
      Heterostructure Composite.
AB  - Vanadium oxides are promising anode materials for lithium-ion batteries (LIBs)
      due to their high capacity, good safety, and low cost. However, their practical
      application has been deferred by the poor rate capability and cycling stability.
      In this work, we report the designed synthesis of porous V2O3/VO2@carbon
      heterostructure electrode for high-performance LIBs. The synergic effects of
      porous nanostructures, phase hybridization with self-building electric field at
      heterointerface, and conductive carbon implantation effectively enhance the
      electronic/ionic conduction and buffer the volume variation in the composite
      material. Electrochemical tests reveal that the composite electrode exhibits high
      Li-ion storage capacities of 503 and 453 mAh/g at 100 and 500 mA/g, as well as
      good cycling stability with a retained capacity of 569 mAh/g over 105 cycles at
      100 mA/g. In-depth kinetics analysis discloses that pseudocapacitive Li-ion
      storage process dominates in the composite electrode, which is probably enabled
      by efficient coupling of the heterostructure components. The strategy of in situ
      carbon implantation and phase hybridization presented herein may be extended to
      other electrode materials for rechargeable batteries with superior
      electrochemical properties.

PMID- 29192755
TI  - Tumor-Targeted Accumulation of Ligand-Installed Polymeric Micelles Influenced by
      Surface PEGylation Crowdedness.
AB  - With respect to the intriguing biocompatibility and the stealthy functions of
      poly(ethylene glycol) (PEG), PEGylated nanoparticulates have been intensively
      engineered for utilities as drug delivery vehicles. To advocate the targeted drug
      transportation, targeting ligands were strategically installed onto the surface
      of PEGylated nanoparticulates. The previous in vitro investigations revealed that
      the ligand-specified cell endocytosis of nanoparticulates was pronounced for the
      nanoparticulates with adequately high PEG crowdedness. The present study aims to
      explore insight into the impact of PEGylation degree on in vivo tumor-targeted
      accumulation activities of cRGD-installed nanoparticulates. The subsequent
      investigations verified the importance of the PEGylation crowdedness in pursuit
      of prolonged retention in the blood circulation post intravenous administration.
      Unprecedentedly, the PEGylation crowdedness was also identified as a crucial
      important parameter to pursue the tumor-targeted accumulation. A plausible reason
      is the elevated PEGylation crowdedness eliciting the restricted involvement in
      nonspecific protein adsorption of nanoparticulates in the biological milieu and
      consequently pronouncing the ligand-receptor-mediated binding for the
      nanoparticulates. Noteworthy was the distinctive performance of the class of the
      proposed systems once utilized for transportation of the mRNA payload to the
      tumors. The protein expression in the targeted tumors appeared to follow a clear
      PEGylation crowdedness dependence manner, where merely 2-fold PEGylation
      crowdedness led to remarkably 10-fold augmentation in protein expression in
      tumors. Hence, the results provided important information and implications for
      design of active-targeting PEGylated nanomaterials to fulfill the targeting
      strategies in systemic applications.

PMID- 29192756
TI  - Synthesis of Si-Induced MnO/Mn2SiO4@C Cuboids as High-Performance Anodes for
      Lithium-Ion Batteries.
AB  - The exploration of anode materials of lithium-ion batteries (LIBs) is still a
      great challenge because of their low electrical conductivity and poor durability.
      Transition-metal oxides are proposed as a potential alternative, even though
      their dimension and structure greatly affect their electrochemical properties. In
      this study, MnO/Mn2SiO4@C cuboids were prepared via the polymerization-pyrolysis
      process. Larger MnCO3 precursor particles embedded into a monolithic carbon
      framework and formed smaller nanoparticles owing to the inducing effect of Si
      element in phthalocyanino silicon (SiPc), giving MnO/Mn2SiO4@C cuboids. The
      micron-scaled cuboid composite can lead to higher tap density and greater
      electrical performance due to lower interparticle resistance. Therefore, the as
      prepared MnO/Mn2SiO4@C electrode exhibits stable specific capacities of 585.9 and
      423.9 mA h g-1 after 1000 discharge/charge cycles at 1 and 2 A g-1, respectively.
      Meanwhile, an excellent rate capacity of 246.3 mA h g-1 was achieved even at 30 A
      g-1. Additionally, this facile and economical strategy to improve electrode
      performance provides a commercially feasible way for the construction of high
      performance LIBs.

PMID- 29192757
TI  - Innovations in Undergraduate Chemical Biology Education.
AB  - Chemical biology derives intellectual vitality from its scientific interface:
      applying chemical strategies and perspectives to biological questions. There is a
      growing need for chemical biologists to synergistically integrate their research
      programs with their educational activities to become holistic teacher-scholars.
      This review examines how course-based undergraduate research experiences (CUREs)
      are an innovative method to achieve this integration. Because CUREs are course
      based, the review first offers strategies for creating a student-centered
      learning environment, which can improve students' outcomes. Exemplars of CUREs in
      chemical biology are then presented and organized to illustrate the five defining
      characteristics of CUREs: significance, scientific practices, discovery,
      collaboration, and iteration. Finally, strategies to overcome common barriers in
      CUREs are considered as well as future innovations in chemical biology education.

PMID- 29192758
TI  - The Thioesterase Domain in Glycopeptide Antibiotic Biosynthesis Is Selective for
      Cross-Linked Aglycones.
AB  - The biosynthesis of the glycopeptide antibiotics (GPAs)-which include teicoplanin
      and vancomycin-is a complex enzymatic process relying on the interplay of
      nonribosomal peptide synthesis and a cytochrome P450-mediated cyclization
      cascade. This unique cyclization cascade generates the highly cross-linked state
      of these nonribosomal peptides, which is crucial for their antimicrobial
      activity. Given that these essential oxidative transformations occur while the
      peptide remains bound to the terminal module of the nonribosomal peptide
      synthetase (NRPS) machinery, it is important to assess the selectivity of the
      terminal thioesterase (TE) domain and how this domain contributes to the
      maintenance of an efficient biosynthetic pathway while at the same time ensuring
      GPA maturation is completed. In this study, we report the in vitro
      characterization of the thioesterase domain from teicoplanin biosynthesis, the
      first GPA thioesterase to be characterized. Our results show that the activity of
      this TE domain relies on the presence of an unusual extended N-terminal linker
      region that appears to be unique to the NRPS machineries found in GPA
      biosynthesis. In addition, we show that the activity of this domain against
      carrier protein bound substrates is dramatically enhanced for mature GPA
      aglycones as opposed to linear peptides and partially cyclized intermediates.
      These results demonstrate how the interplay between NRPS and P450s during late
      stage GPA biosynthesis is not only maintained but also leads to the efficient
      production of mature GPA aglycones. Thus, GPA TE domains represent another
      impressive example of the ability of TE domains to act as logic gates during NRPS
      biosynthesis, ensuring that essential late-stage peptide modifications are
      completed before catalyzing the release of the mature, bioactive peptide product.

PMID- 29192759
TI  - Sulfur Nanoparticles with Novel Morphologies Coupled with Brain-Targeting
      Peptides RVG as a New Type of Inhibitor Against Metal-Induced Abeta Aggregation.
AB  - Functionalized nanomaterials, which have been applied widely to inhibit amyloid
      beta protein (Abeta) aggregation, show enormous potential in the field of
      prevention and treatment of Alzheimer's disease (AD). A significant body of data
      has demonstrated that the morphology and size of nanomaterials have remarkable
      effects on their biological behaviors. In this work, we proposed and designed
      three kinds of brain-targeting sulfur nanoparticles (RVG@Met@SNPs) with novel
      morphologies (volute-like, tadpole-like, and sphere-like) and investigated the
      effect of different RVG@Met@SNPs on Abeta-Cu2+ complex aggregation and their
      corresponding neurotoxicity. Among them, the sphere-like nanoparticles
      (RVG@Met@SS) exhibited the most effective inhibitory activity, due to their
      unique mini size effect, and they reduced 61.6% the Abeta-Cu2+ complex
      aggregation and increased 92.4% SH-SY5Y cell viability in a dose of 10 MUg/mL. In
      vitro and in vivo, the abilities of different morphologies of RVG@Met@SNPs to
      cross the blood-brain barrier (BBB) and target brain parenchymal cells were
      significantly different. Moreover, improvements in learning disability and
      cognitive loss were shown in the transgenic AD mice model using the Morris water
      maze test after multiple doses of RVG@Met@SNPs treatment. In general, the purpose
      of this research is to develop a biological application of sulfur nanoparticles
      and to provide a novel functionalized nanomaterial to treat AD.

PMID- 29192760
TI  - Flexible Black-Phosphorus Nanoflake/Carbon Nanotube Composite Paper for High
      Performance All-Solid-State Supercapacitors.
AB  - We proposed a simple route for fabrication of the flexible BP nanoflake/carbon
      nanotube (CNT) composite paper as flexible electrodes in all-solid-state
      supercapacitors. The highly conductive CNTs not only play a role as active
      materials but also increase conductivity of the hybrid electrode, enhance
      electrolyte shuttling and prevent the restacking between BP nanoflakes. The
      fabricated flexible all-solid-state supercapacitor (ASSP) device at the mass
      proportion of BP/CNTs 1:4 was found to deliver the highest volumetric capacitance
      of up to 41.1 F/cm3 at 0.005 V/s, superior to the ASSP based on the bare graphene
      or BP. The BP/CNTs (1:4) device delivers a rapid charging/discharging up to 500
      V/s, which exhibits the characteristic of a high power density of 821.62 W/cm3,
      while having outstanding mechanical flexibility and high cycling stability over
      10 000 cycles (91.5% capacitance retained). Moreover the BP/CNTs (1:4) ASSP
      device still retains large volumetric capacitance (35.7 F/cm3 at the scan rate of
      0.005 V/s) even after 11 months. In addition, the ASSP of BP/CNTs (1:4) exhibits
      high energy density of 5.71 mWh/cm3 and high power density of 821.62 W/cm3. As
      indicated in our work, the strategy of assembling stacked-layer composites films
      will open up novel possibility for realizing BP and CNTs in new-concept thin-film
      energy storage devices.

PMID- 29192762
TI  - Correction to Digital Bioassays: Theory, Applications, and Perspectives.

PMID- 29192761
TI  - Scalable Synthesis of Honeycomblike V2O5/Carbon Nanotube Networks as Enhanced
      Cathodes for Lithium-Ion Batteries.
AB  - A green and scalable route to form a honeycomblike macroporous network by
      homogeneously weaving V2O5 nanowires and carbon nanotubes (CNTs) was developed.
      The intertwinement between V2O5 nanowires and CNTs not only integrates nanopores
      into the macroporous system but also elevates the collection and transfer of
      charges through the conductive network. The unique combination of V2O5 nanowires
      and CNTs renders the composite monolith with synergic properties for
      substantially enhancing electrochemical kinetics of lithiation/delithiation when
      used as a lithium-ion battery (LIB) cathode. This work presents a useful approach
      for a large-scale production of cellular monoliths as high-performance LIB
      cathodes.

PMID- 29192763
TI  - Assessing Cumulative Effects of Climate Change Manipulations on Phosphorus
      Limitation in a Californian Grassland.
AB  - Grasslands throughout the world are responding in diverse ways to changing
      climate and environmental conditions. In this study we analyze indicators of
      phosphorus limitation including phosphorus concentrations, phosphorus to
      nitrogen, and carbon ratios, oxygen isotope ratios of phosphate in vegetation,
      and phosphatase enzyme activity in soil to shed light on potential effects of
      climate change on phosphorus availability to grassland vegetation. The study was
      conducted at the Jasper Ridge Global Change Experiment (JRGCE), California where
      manipulations mimicking increases in temperature, water, nitrogen and carbon
      dioxide have been maintained for over 15 years. We compare our results to an
      earlier study conducted 3 years after the start of the experiment, in order to
      assess any change in the response of phosphorus over time. Our results suggest
      that a decade later the measured indicators show similar or only slightly
      stronger responses. Specifically, addition of nitrogen, the principle parameter
      controlling biomass growth, increased phosphorus demand but thresholds that
      suggest P limitation were not reached. A study documenting changes in net primary
      productivity (NPP) over time at the JRGCE also could not identify a progressive
      effect of the manipulations on NPP. Combined these results indicate that the
      vegetation in these grassland systems is not very sensitive to the range of
      climate parameters tested.

PMID- 29192764
TI  - Light Control of Protein Solubility Through Isoelectric Point Modulation.
AB  - We previously described the photoactivated depot or PAD approach that allows for
      the light control of therapeutic protein release. This approach relies on the
      ability to use light to change a protein's solubility. Traditionally this was
      accomplished by linking the protein to an insoluble but injectable polymer via a
      light cleaved linker. This allows the injected material to remain at the site of
      injection, until transcutaneous irradiation breaks the link between polymer and
      protein, permitting the protein to be absorbed. However, there are multiple
      problems associated with polymer based approaches: The polymer makes up a
      majority of the material, making it inefficient. In addition, after protein
      release, the polymer has to be cleared from the body, a significant design
      challenge. In this work, we create materials that form photoactivated depots of
      insulin without the need for polymers, by linking photolysis to an isoelectric
      point shift, which itself is linked to a solubility shift. Specifically, we
      linked basic groups to insulin via a light cleaved linker. These shift the normal
      pI of insulin from 5.4 to approximately 7. The result of this incorporation are
      materials that are completely soluble in mildly acidic solutions but precipitate
      upon injection into a pH 7 environment, i.e., the skin. We successfully
      synthesized four such modified insulins, demonstrating that their pI values were
      shifted in the expected manner. We then analyzed one of them, P2-insulin, in
      detail, demonstrating that it behaves as designed: It is soluble in a formulation
      pH of 4, but precipitates at pH 7.2, its approximate pI value. Upon irradiation,
      the photocleavable link to insulin is broken, and completely native and soluble
      insulin is released from the depot in a well behaved, first order fashion. These
      materials are 90% therapeutic, form completely soluble and injectable
      formulations in mildly acidic conditions, form insoluble depots at neutral pH,
      efficiently release soluble protein from these depots when irradiated, and leave
      behind only small easily absorbed molecules after irradiation. As such they
      approach ideality for photoactivated depot materials.

PMID- 29192765
TI  - Development of an in Vitro-Based Risk Assessment Framework for Predicting Ambient
      Particulate Matter-Bound Polycyclic Aromatic Hydrocarbon-Activated Toxicity
      Pathways.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widely distributed throughout the
      atmosphere as mixtures attached to ambient particulate matter (PM). PAHs usually
      elicit similar toxicological pathways but do so with varying levels of efficacy.
      In this study, we utilized high-throughput screening (HTS) in vitro data of PAHs
      to predict health risks associated with coarse and fine PM. PM samples with 22
      PAH compounds obtained from residential areas close to industrial parks in
      central Taiwan were analyzed. On the basis of the PM-bound PAH concentrations and
      their activities reported in HTS assays, we developed a probabilistic model for
      estimating cumulative exposure of humans to PAHs. Activity-to-exposure ratio
      (AER) values were calculated to compare relative risks of activating the aryl
      hydrocarbon receptor (AhR), nuclear factor erythroid 2-related factor 2 (Nrf2),
      and tumor suppressor gene (p53) when children or adults were exposed to fine or
      coarse PM in different seasons. On the basis of AER values, the risk of fine PM
      exposure was relatively higher than the risk of exposure to coarse PM in pathway
      activation. Children as a susceptible population had a risk of the activating AhR
      pathway greater than that of adults. Particularly higher risks were observed in
      winter than in summer. Among three pathways, AhR was the most sensitive one
      activated by exposure to PAHs. In addition, the activation of the AhR, Nrf2, and
      p53 pathways was compared by in vitro reporter assays with and without the pre
      extraction of PAHs from PM. Our proposed novel approach accounts for mixture
      toxicities in characterizing in vitro pathway-based risks via inhalation exposure
      to ambient PAHs.

PMID- 29192766
TI  - Cation-Exchanged Zeolitic Chalcogenides for CO2 Adsorption.
AB  - We report here the intrinsic advantages of a special family of porous
      chalcogenides for CO2 adsorption in terms of high selectivity of CO2/N2, large
      uptake capacity, and robust structure due to their first-ever unique integration
      of the chalcogen-soft surface, high porosity, all-inorganic crystalline
      framework, and the tunable charge-to-volume ratio of exchangeable cations.
      Although tuning the CO2 adsorption properties via the type of exchangeable
      cations has been well-studied in oxides and MOFs, little is known about the
      effects of inorganic exchangeable cations in porous chalcogenides, in part
      because ion exchange in chalcogenides can be very sluggish and incomplete due to
      their soft character. We have demonstrated that, through a methodological change
      to progressively tune the host-guest interactions, both facile and nearly
      complete ion exchange can be accomplished. Herein, a series of cation-exchanged
      zeolitic chalcogenides (denoted as M@RWY) were studied for the first time for CO2
      adsorption. Samples were prepared through a sequential ion-exchange strategy, and
      Cs+-, Rb+-, and K+-exchanged samples demonstrated excellent CO2 adsorption
      performance. Particularly, K@RWY has the superior CO2/N2 selectivity with the N2
      adsorption even undetected at either 298 or 273 K. It also has the large uptake
      of 6.3 mmol/g (141 cm3/g) at 273 K and 1 atm with an isosteric heat of 35-41 kJ
      mol-1, the best among known porous chalcogenides. Moreover, it permits a facile
      regeneration and exhibits an excellent recyclability, as shown by the
      multicycling adsorption experiments. Notably, K@RWY also demonstrates a strong
      tolerance toward water.

PMID- 29192767
TI  - Trojan Horse for Light-Triggered Bifurcated Production of Singlet Oxygen and
      Fenton-Reactive Iron within Cancer Cells.
AB  - Traditional photodynamic therapy for cancer relies on dye-photosensitized
      generation of singlet oxygen. However, therapeutically effective singlet oxygen
      generation requires well-oxygenated tissues, whereas many tumor environments tend
      to be hypoxic. We describe a platform for targeted enhancement of photodynamic
      therapy that produces singlet oxygen in oxygenated environments and hydroxyl
      radical, which is typically regarded as the most toxic reactive oxygen species,
      in hypoxic environments. The 24-subunit iron storage protein bacterioferritin
      (Bfr) has the unique property of binding 12 heme groups in its protein shell. We
      inserted the isostructural photosensitizer, zinc(II) protoporphyrin IX (ZnP), in
      place of the hemes and extended the surface-exposed N-terminal ends of the Bfr
      subunits with a peptide targeting a receptor that is hyperexpressed on the cell
      surface of many tumors and tumor vasculature. We then loaded the inner cavity
      with ~2500 irons as a ferric oxyhydroxide polymer and finally conjugated 2 kDa
      polyethylene glycol to the outer surface. We showed that the inserted ZnP
      photosensitizes generation of both singlet oxygen and the hydroxyl radical, the
      latter via the reaction of photoreleased ferrous iron with hydrogen peroxide.
      This targeted iron-loaded ZnP-Bfr construct was endocytosed by C32 melanoma cells
      and localized to lysosomes. Irradiating the treated cells with light at
      wavelengths overlapping the ZnP Soret absorption band induced photosensitized
      intracellular Fe2+ release and substantial lowering of cell viability. This
      targeted, light-triggered production of intracellular singlet oxygen and Fenton
      reactive iron could potentially be developed into a phototherapeutic adjunct for
      many types of cancers.

PMID- 29192768
TI  - Mavyret: A Pan-Genotypic Combination Therapy for the Treatment of Hepatitis C
      InfectionPublished as part of the Biochemistry series "Biochemistry to Bedside".

PMID- 29192769
TI  - Silyl-Hydrosilane Exchange at a Magnesium Triphenylsilyl Complex Supported by a
      Cyclen-Derived NNNN-Type Macrocyclic Ligand.
AB  - The magnesium triphenylsilyl complex [(Me3TACD)Mg(SiPh3)] (2) was synthesized
      from magnesium bis(triphenylsilyl) [Mg(SiPh3)2(THF)2].THF (1; THF =
      tetrahydrofuran) and the NNNN-type macrocyclic amidotriamine proligand (Me3TACD)H
      ((Me3TACD)H = Me3[12]aneN4 = 1,4,7-trimethyl-1,4,7,10-tetraazacyclododecane).
      Treating 2 with AlR3 (R = Me, Et) gave the magnesium triphenylsilyl complexes
      with "blocked" amido function [(Me3TACD.AlR3)Mg(SiPh3)] (3a: R = Me; 3b: R = Et).
      Instead of forming a Mg-H bond upon reaction with dihydrogen or hydrosilanes, 2
      and 3a,b underwent rapid silyl-silane exchange with hydrosilanes. Treating the
      ethyl complex [(Me3TACD.AlEt3)MgEt] with H3SiPh gave [(Me3TACD.AlEt3)MgH] (4),
      albeit not in a reproducible manner. The silyl-hydrosilane exchange allows access
      to other magnesium silyls of the type [(Me3TACD)Mg(SiR'3)] (5a: SiR'3 = SiH2Ph;
      5b: SiR'3 = SiHPh2) and [(Me3TACD.AlR3)Mg(SiR'3)] (6a: SiR'3 = SiH2Ph, R = Me;
      6b: SiR'3 = SiH2Ph, R = Et; 7a: SiR'3 = SiHPh2, R = Me; 7b: SiR'3 = SiHPh2, R =
      Et). The reaction of 2 with H2SiMePh in THF at room temperature resulted in an
      equilibrium (Keq ~ 1). Protonolysis of 2 with Bronsted acids (HX) 2,5-di-tert
      butylphenol, phenylacetylene, acetophenone, aniline, and triethylammonium
      chloride each gave a compound [(Me3TACD)Mg(X)] with the conjugated base
      coordinated at the magnesium along with HSiPh3. The magnesium silyls 1, 2, and 7b
      as well as the magnesium hydride 4 contain a distorted square-pyramidal magnesium
      center according to single-crystal X-ray diffraction.

PMID- 29192770
TI  - Dioxygen in Polyoxometalate Mediated Reactions.
AB  - In this review article, we consider the use of molecular oxygen in reactions
      mediated by polyoxometalates. Polyoxometalates are anionic metal oxide clusters
      of a variety of structures that are soluble in liquid phases and therefore
      amenable to homogeneous catalytic transformations. Often, they are active for
      electron transfer oxidations of a myriad of substrates and upon reduction can be
      reoxidized by molecular oxygen. For example, the phosphovanadomolybdate,
      H5PV2Mo10O40, can oxidize Pd(0) thereby enabling aerobic reactions catalyzed by
      Pd and H5PV2Mo10O40. In a similar vein, polyoxometalates can stabilize metal
      nanoparticles, leading to additional transformations. Furthermore, electron
      transfer oxidation of other substrates such as halides and sulfur-containing
      compounds is possible. More uniquely, H5PV2Mo10O40 and its analogues can mediate
      electron transfer-oxygen transfer reactions where oxygen atoms are transferred
      from the polyoxometalate to the substrate. This unique property has enabled
      correspondingly unique transformations involving carbon-carbon, carbon-hydrogen,
      and carbon-metal bond activation. The pathway for the reoxidation of
      vanadomolybdates with O2 appears to be an inner-sphere reaction, but the
      oxidation of one-electron reduced polyoxotungstates has been shown through
      intensive research to be an outer-sphere reaction. Beyond electron transfer and
      electron transfer-oxygen transfer aerobic transformations, there a few examples
      of apparent dioxygenase activity where both oxygen atoms are donated to a
      substrate.

PMID- 29192771
TI  - Phenolic Substances from Ocimum Species Enhance Glucose-Stimulated Insulin
      Secretion and Modulate the Expression of Key Insulin Regulatory Genes in Mice
      Pancreatic Islets.
AB  - Ocimum gratissimum and Ocimum basilicum are plants ethnopharmacologically used to
      treat diabetes mellitus, a life-threatening disease that affects millions of
      people worldwide. In order to further understand their antidiabetic potential,
      which has been previously demonstrated in animal models, we aimed to investigate
      the acute and chronic effects of major phenolic substances from both plants on
      insulin secretion and gene expression in pancreatic islets isolated from NMRI
      mice. Insulin secretion was measured after acute (1 h) and long-term (72 h)
      incubation of islets with one of four cinnamic acid derivatives (caftaric,
      caffeic, chicoric, and rosmarinic acids) or a C-glucosylated flavonoid (vicenin
      2). All substances acutely enhanced glucose-stimulated insulin secretion (GSIS)
      from islets at concentrations from 10-10 to 10-6 M. They also increased GSIS
      after chronic incubation (10-8 M). None of them increased insulin secretion in
      the presence of low glucose concentration. Furthermore, these substances markedly
      changed the gene expression profile of key insulin regulatory genes INS1, INS2,
      PDX1, INSR, IRS1, and proliferative genes as well as glucose transporter 2
      (GLUT2), in treated islets. Thus, they may play an important role in diabetes
      treatment. This is the first report on the insulin-secretory activity of caftaric
      acid, rosmarinic acid, and vicenin-2.

PMID- 29192772
TI  - Facile Synthesis of Flowerlike LiFe5O8 Microspheres for Electrochemical
      Supercapacitors.
AB  - Facile synthesis of porous and hollow spinel materials is very urgent due to
      their extensive applications in the field of energy storage. In present work,
      flowerlike porous LiFe5O8 microspheres etched for 15, 30, and 45 min (named as p
      LFO-15, p-LFO-30, and p-LFO-45, respectively) are successfully synthesized
      through a facile chemical etching method based on bulk LiFe5O8 (LFO) particles as
      precursors, and they are applied as electrode materials for high-performance
      electrochemical capacitors. In particular, the specific surface area of p-LFO-45
      reaches 46.13 m2 g-1, which is 112 times greater than that of the unetched
      counterpart. Therefore, the p-LFO-45 electrode can achieve a higher capacitance
      of 278 F g-1 at a scan rate of 5 mV s-1 than the unetched counterpart.
      Furthermore, the p-LFO-45 electrode presents a good cycling stability with 78.3%
      of capacitive retention after 2000 cycles, which is much higher than that of the
      unetched LFO particles (66%). Therefore, the flowerlike porous LFO microspheres
      are very promising candidate materials for supercapacitor applications.

PMID- 29192773
TI  - Activity of Tumor Necrosis Factor alpha Is Modulated by Dynamic Conformational
      Rearrangements.
AB  - The homotrimeric ligand tumor necrosis factor alpha (TNFalpha) is a key cytokine
      and immune regulator; however, when deregulated, it leads to several major
      chronic inflammatory diseases. Perturbation of the protein-protein interface has
      proven to be an efficient strategy to inactivate TNFalpha, but the atomic
      resolution mechanism of its inactivation remains poorly understood. Here, we
      probe the solution structure and dynamics of active and inactive TNFalpha using
      NMR spectroscopy. The data reveal that TNFalpha undergoes motions on different
      time scales. Furthermore, by site-directed mutagenesis of residues at the
      trimerization interface and by targeting the interface with a low molecular
      weight inhibitor, we show that TNFalpha retains its overall structure and
      trimeric state. However, upon perturbation, TNFalpha exhibits increased
      conformational dynamics spanning from the trimerization interface to the regions
      mediating receptor binding. These findings provide novel insights into the
      inactivation mechanism of TNFalpha and the basis for strategies to target
      TNFalpha activity.

PMID- 29192774
TI  - Nitrogen-Containing Volatiles from Marine Salinispora pacifica and Roseobacter
      Group Bacteria.
AB  - Bacteria can produce a wide variety of volatile compounds. Many of these
      volatiles carry oxygen, while nitrogen-containing volatiles are less frequently
      observed. We report here on the identification and synthesis of new nitrogen
      containing volatiles from Salinispora pacifica CNS863 and explore the occurrence
      in another bacterial lineage, exemplified by Roseobacter-group bacteria. Several
      compound classes not reported before from bacteria were identified, such as
      dialkyl ureas and oxalamides. Sulfinamides have not been reported before as
      natural products. The actinomycete S. pacifica CNS863 produces, for example,
      sulfinamides N-isobutyl- and N-isopentylmethanesulfinamide (5, 6), urea N,N'
      diisobutylurea (16), and oxalamide N,N'-diisobutyloxalamide (17). In addition,
      new imines such as (E)-1-(furan-2-yl)-N-(2-methylbutyl)methanimine (8) and (E)-2
      ((isobutylimino)methyl)phenol (13) were identified together with several other
      imines, acetamides, and formamides. Some of these compounds including the
      sulfinamides were also released by the Roseobacter-group bacteria Roseovarius
      pelophilus G5II, Pseudoruegeria sp. SK021, and Phaeobacter gallaeciensis BS107,
      although generally fewer compounds were detected. These nitrogen-containing
      volatiles seem to originate from biogenic amines derived from the amino acids
      valine, leucine, and isoleucine.

PMID- 29192775
TI  - Stable Push-Pull Disilene: Substantial Donor-Acceptor Interactions through the
      Si?Si Double Bond.
AB  - The push-pull effect has been widely used to effectively tune pi-electron
      systems. Herein, we report the synthesis and properties of 1-amino-2
      boryldisilene 1 as the first push-pull disilene. Its spectroscopic and structural
      features show substantial interactions between the Si?Si double bond and the
      amino and boryl substituents. The pi -> pi* absorption band of 1 is remarkably
      red-shifted compared to that of the corresponding alkyl-substituted disilene 2.
      Treatment of 1 with H2 resulted in the cleavage of two molecules of H2 under
      concomitant formation of the corresponding trihydridodisilane and hydroborane.

PMID- 29192776
TI  - A Phosphosilicate Compound, NaCa3PSiO8: Structure Solution and Luminescence
      Properties.
AB  - NaCa3PSiO8 was synthesized in a microwave-assisted solid-state reaction. The
      crystal structure of the synthesized compound was solved using a least-squares
      method, followed by simulated annealing. The compound was crystallized in the
      orthorhombic space group Pna21, belonging to Laue class mmm. The structure
      consisted of two layers of cation planes, each of which contained three cation
      channels. The cation channels in each of the layers ran antiparallel to that of
      the adjacent layer. All the major cations together constituted four distinct
      crystallographic sites. The Rietveld refinement of the powder X-ray diffraction
      data, followed by the maximum-entropy method analysis, confirmed the obtained
      structure solutions. The electronic band structure of the compound was analyzed
      through density function theory calculations. Luminescence properties of the
      compound, upon activating with Eu2+ ions, were analyzed through photoluminescence
      measurements and decay profile analysis. The compound was found to exhibit green
      luminescence centered at ~502 nm, with a typical broadband emission due to the
      transition from the crystal-field split 4f65d to 4f7 levels.

PMID- 29192777
TI  - Iron-Catalyzed 1,2-Selective Hydroboration of N-Heteroarenes.
AB  - A N2-bridged diiron complex [Cp*(Ph2PC6H4S)Fe]2(MU-N2) (1) has been found to
      catalyze the hydroboration of N-heteroarenes with pinacolborane, giving N
      borylated 1,2-reduced products with high regioselectivity. The catalysis is
      initiated by coordination of N-heteroarenes to the iron center, while the B-H
      bond cleavage is the rate-determining step.

PMID- 29192778
TI  - Addition and Correction to Multifunctional Cytochrome c: Learning New Tricks from
      an Old Dog.

PMID- 29192779
TI  - Structure and Bonding in Uranyl(VI) Peroxide and Crown Ether Complexes;
      Comparison of Quantum Chemical and Experimental Data.
AB  - The structure, chemical bonding, and thermodynamics of alkali ions in M[12-crown
      4]+, M[15-crown-5]+, and M[18-crown-6]+, M[UO2(O2)(OH2)2]+4,5, and
      M[UO2(O2)(OH)(OH2)]n1-n (n = 4, 5) complexes have been explored by using quantum
      chemical (QC) calculations at the ab initio level. The chemical bonding has been
      studied in the gas phase in order to eliminate solvent effects. QTAIM analysis
      demonstrates features that are very similar in all complexes and typical for
      electrostatic M-O bonds, but with the M-O bonds in the uranyl peroxide systems
      about 20 kJ mol-1 stronger than in the corresponding crown ether complexes. The
      regular decrease in bond strength with increasing M-O bond distance is consistent
      with predominantly electrostatic contributions. Energy decomposition of the
      reaction energies in the gas phase and solvent demonstrates that the predominant
      component of the total attractive (DeltaEelec + DeltaEorb) energy contribution is
      the electrostatic component. There are no steric constraints for coordination of
      large cations to small rings, because the M+ ions are located outside the ring
      plane, [On], formed by the oxygen donors in the ligands; coordination of ions
      smaller than the ligand cavity results in longer than normal M-O distances or in
      a change in the number of bonds, both resulting in weaker complexes. The Gibbs
      energies, enthalpies, and entropies of reaction calculated using the conductor
      like screening model, COSMO, to account for solvent effects deviate significantly
      from experimental values in water, while those in acetonitrile are in much better
      agreement. Factors that might affect the selectivity are discussed, but our
      conclusion is that present QC methods are not accurate enough to describe the
      rather small differences in selectivity, which only amount to 5-10 kJ mol-1. We
      can, however, conclude on the basis of QC and experimental data that M[crown
      ether]+ complexes in the strongly coordinating water solvent are of outer-sphere
      type, [M(OH2)n+][crown ether], while those in weakly coordinating acetonitrile
      are of inner-sphere type, [M-crown ether]+. The observation that the
      M[UO2(O2)(OH)(OH2)]n1-n complexes are more stable in solution than those of
      M[crown ether]+ is an effect of the different charges of the rings.

PMID- 29192780
TI  - Strategy for Modeling the Electrostatic Responses of the Spectroscopic Properties
      of Proteins.
AB  - For better understanding and more efficient use of the spectroscopic probes
      (vibrational and NMR) of the local electrostatic situations inside proteins,
      appropriate modeling of the properties of those probes is essential. The present
      study is devoted to examining the strategy for constructing such models. A more
      well-founded derivation than the ones in previous studies is given in
      constructing the models. Theoretical analyses are conducted on two representative
      example cases related to proteins, i.e., the peptide group of the main chains and
      the CO and NO ligands to the Fe2+ ion of heme, with careful treatment of the
      behavior of electrons in the electrostatic responses and with verification of
      consistency with observable quantities. It is shown that, for the stretching
      frequencies and NMR chemical shifts, it is possible to construct reasonable
      electrostatic interaction models that encompass the situations of hydration and
      uniform electric field environment and thus are applicable also to the cases of
      nonuniform electrostatic situations, which are highly expected for inside of
      proteins.

PMID- 29192781
TI  - Size-Dependent Phase Transfer Functionalization of Gold Nanoparticles To Promote
      Well-Ordered Self-Assembly.
AB  - We present a route for the functionalization of gold nanoparticles (AuNP) based
      on phase transfer functionalization in order to optimize the stability and the
      potential for self-assembly. Depending on the desired size, different ligand
      exchanges have to be employed: The maximum AuNP size that can be stabilized
      without concentration loss is 46 nm for polystyrene-based ligands with 5 and 10
      kDa. Small particles <12 nm are better stabilized by smaller ligands. We are able
      to demonstrate that well-ordered close-packed monolayers of 28 nm AuNP covering
      at least 400 MUm2 are possible with a potential for much larger areas. Such
      monolayers are of great interest for various fundamental experiments in the
      context of plasmonics and SERS and for sensor applications.

PMID- 29192782
TI  - Correction to "Modeling the Influence of Fatty Acid Incorporation on Mesophase
      Formation in Amphiphilic Therapeutic Delivery Systems".

PMID- 29192784
TI  - One- or Two-Step Synthesis of C-8 and N-9 Substituted Purines.
AB  - A novel and original strategy to obtain rapidly a large diversity of C-8 and N-9
      substituted purines was developed. The present procedure describes annulation
      reactions in one or two steps starting from 5-aminoimidazole-4-carbonitriles 1-8
      in moderate to good yields. 8,9-Disubstituted-6,9-dihydro-1H-purin-6-ones 9-14, 6
      amino-8,9-disubstituted-3,9-dihydro-2H-purin-2-ones 15-20, 8,9-disubstituted-3,9
      dihydro-2H-purin-2,6-diamines 21-24 and 6-imino-1-phenyl-8,9-disubstituted-6,9
      dihydro-1H-purin-2-(3H)-ones 25-26 were synthesized in one step using formic
      acid, urea, guanidine carbonate, and phenylisocyanate, respectively, whereas 8,9
      disubstituted-9H-purin-6-amines 27-31 and 6-imino-8,9-disubstituted-6,9-dihydro
      1H-purin-1-amines 32-33 were obtained in two steps using formamide and hydrazine,
      respectively.

PMID- 29192783
TI  - Mesodomain and Protein-Associated Solvent Phases with Temperature-Tunable (200
      265 K) Dynamics Surround Ethanolamine Ammonia-Lyase in Globally Polycrystalline
      Aqueous Solution Containing Dimethyl Sulfoxide.
AB  - Electron paramagnetic resonance spectroscopy of the spin probe, TEMPOL, is used
      to resolve solvent phases that surround the ethanolamine ammonia-lyase (EAL)
      protein from Salmonella typhimurium at low temperature (T) in frozen, globally
      polycrystalline aqueous solution and to report on the T dependence of their
      detectably rigid and fluid states. EAL plays a role in human gut microbiome-based
      disease conditions, and physicochemical studies provide insight into protein
      structure and mechanism, toward potential therapeutics. Temperature dependences
      of the rotational correlation times (tauc; detection range, 10-11 <= tauc <= 10-7
      s) and the corresponding weights of TEMPOL tumbling components from 200 to 265 K
      in the presence of EAL are measured in two frozen systems: (1) water-only and (2)
      1% v/v dimethyl sulfoxide (DMSO). In the water-only condition, a protein-vicinal
      solvent component detectably fluidizes at 230 K and melts the surrounding ice
      crystalline region with increasing T, creating a bounded, relatively high
      viscosity aqueous solvent domain, up to 265 K. In the EAL, 1% v/v DMSO condition,
      two distinct concentric solvent phases are resolved around EAL: protein
      associated domain (PAD) and mesodomain. The DMSO aqueous mesodomain fluidizes at
      200 K, followed by PAD fluidization at 210 K. The interphase dynamical coupling
      is consistent with the spatial arrangement and significant contact areas of the
      phases, indicated by the experimentally determined mean volume ratio,
      V(mesodomain)/V(PAD)/V(protein) = 0.5:0.3:1.0. The results provide a rationale
      for native chemical reactions of EAL at T < 250 K and an advance toward precise
      control of solvent dynamics as a tunable parameter for quantifying the coupling
      between solvent and protein fluctuations and chemical reaction steps in EAL and
      other enzymes.

PMID- 29192785
TI  - Esters as Alkynyl Acyl Ammonium and Azolium Precursors: A Formal [2 + 3]
      Annulation with Amidomalonates via Lewis Base/Lewis Acid Cooperative Catalysis.
AB  - Esters are for the first time used as alpha,beta-unsaturated alkynyl acyl
      ammonium and azolium precursors to undergo a formal [2 + 3] annulation with
      amidomalonates through DMAP/LiCl or carbene/LiCl cooperative catalysis. A wide
      range of (Z)-5-amino-3-furanones were obtained in moderate to high yields with
      high regioselectivity and stereoselectivity. In addition, a plausible mechanism
      based on the calculated charge distribution of the intermediates is proposed to
      explain the regioselectivity.

PMID- 29192786
TI  - Synthesis of 2-Pyridinemethyl Ester Derivatives from Aldehydes and 2
      Alkylheterocycle N-Oxides via Copper-Catalyzed Tandem Oxidative Coupling
      Rearrangement.
AB  - Successful benzylic C(sp3)-H acyloxylation of 2-alkylpyridine, 2-alkylpyrazine,
      and 2-alkylthiazole compounds was achieved using simple aldehydes. This was
      carried out via a copper-catalyzed tandem reaction, involving oxidative
      esterification followed by O-atom transfer of the resultant high yield formed
      Boekelheide intermediate. The method enables the preparation of functional
      heterocycles and the desymmetrization of 2,6-dialkylpyridines for efficient
      synthesis of dissymmetric pincer ligands, thus offering a new life for more
      practical Boekelheide rearrangement.

PMID- 29192787
TI  - Highly Diastereoselective Cationic Cyclization Reactions Convert a Common
      Monocyclic Enone to Bicyclic Precursors for the Synthesis of Retigeranic Acids A
      and B.
AB  - A novel method is demonstrated for the diastereoselective conversion of a
      monocyclic enone to a pair of bicyclic intermediates which enable the
      stereocontrolled enantioselective syntheses of retigeranic acids A and B.

PMID- 29192788
TI  - Copper-Catalyzed Substitution of alpha-Triflyloxy Nitriles and Esters with
      Silicon Nucleophiles under Inversion of the Configuration.
AB  - A copper-catalyzed nucleophilic displacement of alpha-triflyloxy nitriles and
      esters with silicon nucleophiles allows for the stereospecific generation of
      highly enantioenriched alpha-silylated carboxyl compounds. The enantioselective
      synthesis of alpha-silylated nitriles is unprecedented. The catalytic system
      exhibits good functional group tolerance. The stereochemical course of the
      substitution is shown to proceed with inversion of the configuration. The new
      reaction is an addition to the still limited number of methods for catalytic
      C(sp3)-Si cross-coupling.

PMID- 29192789
TI  - Asymmetric Total Synthesis of (+)-Intricenyne via an Endocyclization Route to
      Oxocane Skeleton.
AB  - The first total synthesis of (+)-intricenyne consisting of an oxocane skeleton
      was achieved via an extremely selective endocyclization strategy. The key
      features of the synthesis include a regio- and diastereoselective epoxide opening
      reaction, concise elaboration of oxocane cores via abnormally selective
      endocyclization ether ring formation, and versatile incorporation of the labile
      functional groups.

PMID- 29192790
TI  - Ni-Catalyzed Dimerization and Arylation of Diarylacetylenes with Arylboronic
      Acids.
AB  - A new, facile, and efficient protocol for the synthesis of polysubstituted
      conjugated 1,3-dienes through Ni-catalyzed tandem dimerization/cross-coupling
      reaction of diarylacetylenes and arylboronic acids in the presence of a catalytic
      amount of B2pin2 has been developed. A series of arynes and arylboronic acids
      with different substituents participated well in this catalytic system, affording
      a variety of useful conjugated 1,3-dienes.

PMID- 29192791
TI  - 3,4,5-Trimethylphenol and Lewis Acid Dual-Catalyzed Cascade Ring
      Opening/Cyclization: Direct Synthesis of Naphthalenes.
AB  - A 3,4,5-trimethylphenol and Lewis acid dual-catalyzed cascade reaction of donor
      acceptor (D-A) cyclopropanes via ring-opening and cyclization is developed. In
      this reaction, a phenolic compound was used as a covalent catalyst for the first
      time. Additionally, control experiments proved that 3,4,5-trimethylphenol
      completed the catalytic cycle by accomplishing the C-C bond cleavage. Using this
      strategy, a wide variety of substituted naphthalenes has been synthesized from D
      A cyclopropanes in moderate to high yields under mild conditions.

PMID- 29192792
TI  - Organo-Catalyzed Asymmetric Michael-Hemiketalization-Oxa-Pictet-Spengler
      Cyclization for Bridged and Spiro Heterocyclic Skeletons: Oxocarbenium Ion as a
      Key Intermediate.
AB  - A Michael-hemiketalization-oxa-Pictet-Spengler cyclization has been developed for
      the construction of chiral bridged and spiro heterocyclic skeletons with one
      spiro stereogenic carbon center and two bridgehead carbon centers, utilizing
      cooperative catalysts of a Takemoto thiourea catalyst and a triflimide. In
      particular, an oxocarbenium ion acts as a key intermediate for this cyclization
      reaction. Additionally, biological evaluation of this type of novel structure has
      revealed obvious antiproliferative activity against some cancer cell lines.

PMID- 29192793
TI  - Iodobenzene-Catalyzed Ortho-Dearomatization and Aromatization-Triggered
      Rearrangement of 2-Allylanilines: Construction of Indolin-3-ylmethanols with High
      Diastereoselectivities.
AB  - An iodobenzene-catalyzed oxidative rearrangement of 2-allylanilines was
      developed. This process involves an ortho-oxidative dearomatization mediated by
      the in situ generated iodine(III) compound and a subsequent aromatization
      triggered rearrangement reaction, leading to the formation of functionalized
      indolin-3-ylmethanols with high diastereoselectivities.

PMID- 29192794
TI  - Relationship between self-care and comprehensive understanding of heart failure
      and its signs and symptoms.
AB  - BACKGROUND: Although incomplete understanding of heart failure and its signs and
      symptoms appears to be a barrier to successful self-care, there are few studies
      examining the relationship between self-care and levels of comprehensive
      understanding of heart failure and its signs and symptoms. AIM: To determine
      whether incomplete understanding of heart failure and its signs and symptoms is
      associated with self-care in heart failure patients who were recently discharged
      from the hospital due to heart failure exacerbation. METHODS: Patients completed
      the nine-item European Heart Failure Self-care Behavior scale and questionnaire
      to assess knowledge of heart failure and its signs and symptoms. Three groups
      were formed by their different levels of understanding of heart failure and its
      signs and symptoms. Multivariable linear regression was used to determine whether
      these three levels of understanding groups predicted self-care after controlling
      for demographic and clinical variables. RESULTS: Of 571 patients 22.1%, 40.1% and
      37.8% had poor, moderate, and complete understanding, respectively. Compared with
      patients in the poor understanding group, patients in complete and moderate
      understanding groups were more likely to have better adherence to self-care
      activities (standardized beta = -0.14, 95% confidence interval -3.41, -0.47;
      standardized beta = -0.19, 95% confidence interval -4.26, -1.23, respectively).
      CONCLUSIONS: Fewer than half of the patients had a comprehensive understanding of
      heart failure and its signs and symptoms, which was associated with poor self
      care. Our study suggests that patient education should include contents to
      promote comprehensive understanding of heart failure and its symptoms, as well as
      the importance of self-care behaviors.

PMID- 29192795
TI  - Evidence of taxonomy for Developmental Topographical Disorientation:
      Developmental Landmark Agnosia Case 1.
AB  - We report Developmental Landmark Agnosia (DLA) in a 6-year-old boy (L.G.) who was
      referred to us for congenital prosopagnosia (see Pizzamiglio et al., 2017 , in
      which both testing and rehabilitation of Congenital Prosopagnosia are reported).
      We investigated his performance using a neuropsychological battery and eye
      movement recordings. The assessment showed the presence of deficits in
      recognizing familiar places (along with Congenital Prosopagnosia), but not common
      objects. Eye movement recordings confirmed his problems in recognizing familiar
      landmarks and misrecognition of unfamiliar places. L.G. is the first evidence of
      a DLA, suggesting identification of taxonomy of navigational disorders in
      Developmental Topographical Disorientation is possible, as in the Acquired
      Topographical Disorientation.

PMID- 29192797
TI  - Test-retest reliability and responsiveness to change of clinical tests of
      physical fitness in patients with acute coronary syndrome included in the
      SWEDEHEART register.
AB  - BACKGROUND: To maximise the benefits obtainable from exercise-based cardiac
      rehabilitation, an evaluation of physical fitness using reliable, clinically
      relevant tests is strongly recommended. Recently, objective tests of physical
      fitness have been implemented in the SWEDEHEART register. The reliability of
      these tests has, however, not been examined for patients with acute coronary
      syndrome. AIMS: The aim of this study was to assess the test-retest reliability
      and responsiveness to change of the symptom-limited bicycle ergometer test, the
      dynamic unilateral heel-lift test and the unilateral shoulder-flexion test in
      patients with acute coronary syndrome. METHODS: In a longitudinal study design, a
      total of 40 patients (mean age 63.8 +/- 9.5 years, five women), with ACS, aged <
      75 years, were included at a university hospital in Sweden. The intra-class
      correlation coefficient (ICC) with a 95% confidence interval, standard error of
      measurement (SEM) and responsiveness in terms of the minimal detectable change
      were calculated. RESULTS: Excellent reliability was found, showing ICC values of
      0.98 (0.96-0.99), SEM 4.71 for the bicycle ergometer test, ICC 0.87 (0.75-0.93),
      SEM 4.62 for the shoulder-flexion test and ICC 0.84 (0.71-0.91), SEM 2.24 for the
      heel-lift test. The minimal detectable change was 13 W, 13 and 6 repetitions for
      the bicycle ergometer test, shoulder-flexion and heel-lift tests respectively.
      CONCLUSIONS: The test-retest reliability of clinical tests evaluating physical
      fitness in patients with acute coronary syndrome included in the SWEDEHEART
      register was excellent. This makes the future comparison and evaluation of
      treatment effects in large unselected clinical populations of acute coronary
      syndrome possible.

PMID- 29192796
TI  - The effect of weight loss on body composition, serum bone markers, and adipokines
      in prepubertal obese children after 1-year intervention.
AB  - : Purpose/Aim: The influence of weight loss on bone turnover and bone quality in
      childhood remains controversial, but it may implicate interactions between
      adiposity and bone metabolism. Therefore, we studied the relationships between
      bone markers and adipokines during weight loss in obese children. MATERIALS AND
      METHODS: We determined serum leptin, soluble leptin receptor, adiponectin, bone
      alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I),
      osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC),
      sclerostin, body composition, and bone mineral density (BMD) in 40 obese
      prepubertal children before and after therapy. The control group, matched for sex
      and age, consisted of 40 non-obese children. RESULTS: We found that values of the
      total body less head-bone mineral content (TBLH-BMC) and TBLH-BMD were
      significantly increased, but TBLH-BMD Z-score was decreased by 25% (p = 0.002) in
      obese children with weight loss after therapy. We observed increases of CTX-I to
      OC ratio (p = 0.009), and Gla-OC concentrations (p = 0.049). Changes in TBLH-BMD
      Z-score in patients were positively correlated with changes in BMI Z-score (p =
      0.001), percentage of fat mass (p = 0.004), and BALP activity (p = 0.01). Changes
      in BALP activity were negatively correlated (p < 0.001) with changes in
      adiponectin concentrations, while changes in sclerostin levels were positively
      correlated (p = 0.001) with leptin changes. CONCLUSIONS: We suggest that
      alterations in adipokines metabolism were associated with a lower rate of bone
      mineral accrual as a result of decreased bone formation rather than increased
      bone resorption. The lower rate of bone mass accrual in weight losing children
      may be an effect of reduced BALP levels related to increase in adiponectin
      levels.

PMID- 29192798
TI  - Does Nutrition Education with Fruit and Vegetable Supplementation Increase Fruit
      and Vegetable Intake and Improve Anthropometrics of Overweight or Obese People of
      Varying Socioeconomic Status?
AB  - Fruit and vegetable (F/V) intake is inadequate and obesity is more prevalent
      among adults of lower socioeconomic status (SES) in the United States. The effect
      of nutrition education and F/V supplementation on F/V intake and anthropometrics
      of overweight or obese adults of varying SES was determined. F/V intake was not
      different between the nutrition education and F/V supplementation groups.
      Individuals with a graduate degree had significant improvements in fruit intake.
      Few of the improvements in anthropometrics seen were significant. Future research
      should focus on specific barriers to F/V intake and include information on total
      energy intake and expenditure.

PMID- 29192799
TI  - Communication as a human right: Citizenship, politics and the role of the speech
      language pathologist.
AB  - According to Article 19 of the Universal Declaration on Human Rights "Everyone
      has the right to freedom of opinion and expression; this right includes freedom
      to hold opinions without interference and to seek, receive and impart information
      and ideas through any media and regardless of frontiers." The purpose of this
      paper is to elucidate communication as a human right in the life of a young man
      called Declan who has Down syndrome. This commentary paper is co-written by
      Declan, his sister who is a speech-language pathologist (SLP) with an advocacy
      role, his SLP, and academics. Declan discusses, in his own words, what makes
      communication hard, what helps communication, his experiences of speech-language
      pathology, and what he knows about human rights. He also discusses his passion
      for politics, his right to be an active citizen and participate in the political
      process. This paper also focuses on the role of speech-language pathology in
      supporting and partnering with people with communication disabilities to have
      their voices heard and exercise their human rights.

PMID- 29192800
TI  - Development of an interprofessional lean facilitator assessment scale.
AB  - High reliability is important for optimising quality and safety in healthcare
      organisations. Reliability efforts include interprofessional collaborative
      practice (IPCP) and Lean quality/process improvement strategies, which require
      skilful facilitation. Currently, no validated Lean facilitator assessment tool
      for interprofessional collaboration exists. This article describes the
      development and pilot evaluation of such a tool; the Interprofessional Lean
      Facilitator Assessment Scale (ILFAS), which measures both technical and 'soft'
      skills, which have not been measured in other instruments. The ILFAS was
      developed using methodologies and principles from Lean/Shingo, IPCP,
      metacognition research and Bloom's Taxonomy of Learning Domains. A panel of
      experts confirmed the initial face validity of the instrument. Researchers
      independently assessed five facilitators, during six Lean sessions. Analysis
      included quantitative evaluation of rater agreement. Overall inter-rater
      agreement of the assessment of facilitator performance was high (92%), and
      discrepancies in the agreement statistics were analysed. Face and content
      validity were further established, and usability was evaluated, through primary
      stakeholder post-pilot feedback, uncovering minor concerns, leading to tool
      revision. The ILFAS appears comprehensive in the assessment of facilitator
      knowledge, skills, abilities, and may be useful in the discrimination between
      facilitators of different skill levels. Further study is needed to explore
      instrument performance and validity.

PMID- 29192801
TI  - Application of near-infrared spectroscopy to optimize dissolution profiles of
      tablets according to the granulation mechanism.
AB  - We developed a method for the optimization of dissolution properties of solid
      oral dosage forms manufacturing using high shear wet granulation (HSWG) by using
      near-infrared spectroscopy (NIRS) with chemometrics in small-scale experiments.
      The changes in rheology and NIR spectra of the granules were monitored to verify
      the granulation mechanism and determine the suitable water amount for model
      formulation during the HSWG. Tablets were manufactured by altering the added
      water amount to investigate the impact of the granulation mechanism on drug
      product qualities. Model formulation granules were prepared with 10-20% w/w water
      in a funicular state, corresponding to the plateau region in score plots obtained
      by principal component analysis (PCA). The dissolution rate of model formulation
      tablets manufactured with more than 20% w/w of water was significantly delayed
      while tablets manufactured with 15% w/w water showed 100% dissolution at 15 min.
      NIRS and PCA are applicable to the optimization of dissolution properties via the
      process understanding of HSWG at the early formulation development stage and
      could facilitate drug development.

PMID- 29192802
TI  - Adhering to the principles of clinical pharmacology - the correct fixed
      combinations of antihypertensive drugs.
AB  - INTRODUCTION: Hypertension is one of the primary modifiable risk factor for
      cardiac and renal diseases with the prevalence around 30-45% of the general
      population, with a steep increase with ageing. The administration of blood
      pressure-lowering drugs is to reduce the risk of major clinical cardiovascular
      outcomes. Hypertension guidelines recommend combination therapy in patients with
      high cardiovascular risk and with subclinical organ damage as well as when
      monotherapy fails. Areas covered: As the etiology of essential hypertension is
      multifactorial, combination therapy using different classes of antihypertensive
      agents have greater effect than each on its own (synergistic effect), may have
      better tolerability (two components minimizing each other's side effects) and
      lead to improved patient compliance. Several studies assess the hypotensive
      efficacy on drug combination; there are also studies on triple drug combination.
      Expert commentary: At present, dual and triple combination therapy is available
      to hypertensive patients with good clinical outcomes, compliance and low profile
      of side effects. It is critical as patients' adherence to the pharmacological
      therapy significantly decreases the risk of long-term adverse events including
      mortality. It appears that combinations not only of hypotensive drugs but also
      with statins (as well as antidiabetics) will be widely used.

PMID- 29192803
TI  - Treating hidradenitis suppurativa with photodynamic therapy.
AB  - Hidradenitis suppurativa is a chronic, recurring, and disabling inflammatory
      condition of the skin. There is no cure for hidradenitis suppurativa and
      treatment must be adapted to each individual patient. Several studies have been
      published since 2004 on the use of photodynamic therapy to treat hidradenitis
      suppurativa. The use of superficial or interstitial illumination with 5-amino
      levulinic acid (5-ALA) or methylene blue (MB) have been proposed. Injecting 5-ALA
      or MB followed by illumination with a fiber optic sensor placed inside the lesion
      appears to be a better method of treating these thick lesions.

PMID- 29192804
TI  - Hecogenin exhibits anti-arthritic activity in rats through suppression of pro
      inflammatory cytokines in Complete Freund's adjuvant-induced arthritis.
AB  - Hecogenin is a steroidal sapogenin isolated from the leaves of Agave genus
      species that plays an important role in the treatment of a variety of
      inflammatory diseases. The aim of the present study was to evaluate the anti
      arthritic activity of hecogenin in Complete Freund's adjuvant-induced arthritis
      in rats. The hecogenin (40 ul of 50 ug/kg, orally) and hecogenin + fluticasone
      (40 ul of 25 ug/kg, each, orally) was tested against Complete Freund's adjuvant
      induced arthritis in rats by evaluating various parameters such as paw volume,
      arthritic score, joint diameter, spleen weight, thymus weight, haematological and
      biochemical parameters and pro-inflammatory cytokines. Histopathological and
      radiological analyzes of ankle joints were also carried out. Treatment of rats
      with hecogenin and its combination elicited significant reduction in paw edema,
      arthritic score and joint diameter. Hecogenin and its combination also inhibited
      joint destruction in histopathological and radiological analyzes of ankle joint.
      Hecogenin and its combination significantly increased the levels of red blood
      cells and hemoglobin but decreased the white blood cell count. The anti-arthritic
      activity was also confirmed with the change in biochemical parameters and
      myeloperoxidase assay. In the present investigation, hecogenin and its
      combination prevent destruction of cartilage and protect synovial membrane with
      improving health status through haematonic properties and down regulation of
      various cytokines. Hence, hecogenin may be a potential therapeutic candidate for
      the treatment of rheumatoid arthritis.

PMID- 29192805
TI  - Social participation for people with communication disability in coffee shops and
      restaurants is a human right.
AB  - Although Article 19 of the Universal Declaration of Human Rights states that
      "everyone has a right to freedom of opinion and expression", for people with
      communication disability this may not be a reality. This commentary shares a
      practical example of how people with communication disabilities together with
      speech-language pathology (SLP) students, academics and clinical staff co
      designed and co-implemented a Communication Awareness Training Programme for
      catering staff to enable communication access in coffee shops and restaurants.
      This is an example of how SLPs can embrace their social responsibility to break
      down barriers for people with communication disabilities. This commentary shares
      the reflections of those involved and how they felt empowered because they had
      learned new skills and made a difference. This commentary highlights the need for
      co-design and co-delivery of programs to raise awareness of communication
      disability among catering staff and how the stories of people with communication
      disabilities served as a catalyst for change. It also highlights the need to SLPs
      to move intervention to a social and community space.

PMID- 29192806
TI  - Impact of Alcohol Tax Increase on Maryland College Students' Alcohol-Related
      Outcomes.
AB  - OBJECTIVE: This study A) assessed whether levels of alcohol-related disciplinary
      actions on college campuses changed among MD college students after the 2011
      Maryland (MD) state alcohol tax increase from 6% to 9%, and B) determined which
      school-level factors impacted the magnitude of changes detected. METHOD: A quasi
      experimental interrupted time series (ITS) analysis of panel data containing
      alcohol-related disciplinary actions on 33 MD college campuses in years 2006
      2013. Negative binomial regression models were used to examine whether there was
      a statistically significant difference in counts of alcohol-related disciplinary
      actions comparing time before and after the tax increase. RESULTS: The ITS
      anaysis showed an insignificant relationship between alcohol-related disciplinary
      actions and tax implementation (beta = -.27; p =.257) but indicated that alcohol
      related disciplinary actions decreased significantly over the time under study
      (beta = -.05; p =.022). DISCUSSION: Alcohol related disciplinary actions did
      decrease over time in the years of study, and this relationship was correlated
      with several school-level characteristics, including school price, school funding
      type, types of degrees awarded, and specialty. School price may serve as a proxy
      mediator or confounder of the effect of time on disciplinary actions.

PMID- 29192807
TI  - Autophagy in advanced low- and high-grade tubular adenocarcinomas of the stomach:
      An ultrastructural investigation.
AB  - Autophagy represents a catabolic process in which cellular protein and organelles
      are engulfed into autophagosomes, digested in lysosomes and reutilized for the
      cellular metabolism. In neoplastic conditions, autophagy may act either as a
      tumour suppressor avoiding the accumulation of damaged proteins and organelles or
      as a mechanism of cell survival promoting the tumour growth. Although enhanced
      autophagy has been reported in hypoxic areas of solid tumors, there are only few
      ultrastructural reports concerning the relationships between autophagy and tumor
      grade. In the present study, we have performed an ultrastructural investigation
      aimed to document autophagy in a cohort of advanced gastric carcinomas of tubular
      type, correlating the observed findings with low and high tumor grade. Among 71
      surgically resected cases of advanced gastric carcinomas, we have selected twelve
      low-grade and thirteen high-grade tubular adenocarcinomas. Autophagic vacuoles
      (AV) were only occasionally found in low-grade tubular carcinomas, while they
      constituted a frequent finding in high-grade ones (p < 0.01). Moreover, in high
      grade tubular adenocarcinomas, our data revealed a morphologic association
      between autophagy and nuclear changes, such as multinucleation, micronucleation
      and nuclear buds, largely considered as ultrastructural aspects of mitotic
      instability. However, an increased autophagy was associated with organelle-poor
      cytoplasm or a senescent phenotype, characterized by lipofuscin granules and
      cytoplasmic vacuoles. In the light of our observations, it may be suggested that
      autophagy should be considered a phenomenon mainly related to the cellular
      differentiation and tumor progression.

PMID- 29192808
TI  - A splice-site variant in FLVCR1 produces retinitis pigmentosa without posterior
      column ataxia.
AB  - FLVCR1 (feline leukemia virus subgroup c receptor 1) is a transmembrane protein
      involved in the trafficking of intracellular heme. Homozygous variants in FLVCR1
      have been described in association with a clinical syndrome of posterior column
      ataxia with retinitis pigmentosa (PCARP). Here, we describe a patient with non
      syndromic retinitis pigmentosa homozygous for a splice-site variant in FLVCR1
      (c.1092 + 5G>A) without evidence of posterior column ataxia or cerebellar
      degeneration. We suggest an association between intronic splice-site variants in
      FLVCR1 and the absence of posterior column degeneration and suggest a hypothesis
      to explain this observation. Should this association be proven, it would provide
      valuable prognostic information for patients. Retinal degeneration appears to be
      the sole clinical manifestation of this FLVCR1 variant; gene therapy approaches
      using an adeno-associated viral vector with sub-retinal delivery may therefore
      represent a therapeutic approach to halting retinal degeneration in this patient
      group.

PMID- 29192809
TI  - Kidney carcinoid tumor: Histological, immunohistochemical and ultrastructural
      features.
AB  - Primary carcinoid tumor of the kidney is uncommon. Only limited morphologic
      studies have been reported in the literature. In general, renal carcinoid tumor
      reveals typical morphological features as present in carcinoid tumors in the
      other organs, i.e. growing as trabeculae intermixed with nests of monotonous
      cuboidal cells that show "salt and pepper" nuclear appearance. As reported in
      other organs, different morphological expressions may also present in renal
      carcinoid tumors, such as papillary, pseudoglandular or solid growth patterns and
      clear/eosinophilic cytoplasmic changes. These morphological variations may mimic
      other benign and malignant primary neoplasms in the kidney. Therefore, in some
      cases, ancillary studies are necessary or even crucial to differentiate carcinoid
      tumors from other primary renal neoplasms. Herewith, we report two primary renal
      carcinoid tumors with long follow-up, one showed typical morphological features
      of carcinoid tumor, and the second one revealed some uncommon histological
      findings. To differentiate these carcinoid tumors from other primary renal
      neoplasms and confirm neuroendocrine differentiation, immunohistochemical studies
      are valuable. In case 2 immunohistochemical stain results were not definitive and
      electron microscopy was performed confirming the diagnosis of carcinoid tumor.

PMID- 29192810
TI  - Histological and ultrastructural evaluation of human decellularized matrix as a
      hernia repair device.
AB  - Recently, interest has been increasing for human decellularized matrices, due to
      their ability to reduce numerous side effects related to hernia repair. To date,
      only animal studies investigated the biological interaction post-implant of human
      decellularized matrices for soft tissue repair. Therefore, the aim of this study
      was to evaluate the morphological response one year post implant of human
      decellularized matrix, through morphological analysis of human biopsies. The
      histological and ultrastructural results revealed a perfect cellular repopulation
      and neoangiogenesis, with minimal inflammatory response and a well-organized
      collagen matrix. The results have indicated that this scaffold can be an
      effective treatment for hernia.

PMID- 29192811
TI  - Effects of vitamin D on ovary in DHEA-treated PCOS rat model: A light and
      electron microscopic study.
AB  - AIM: The aim of this study was to investigate the effects of vitamin D treatment
      on ovary in experimentally designed polycystic ovary syndrome of female rats
      using light and electron microscopic techniques. METHODS: Twenty-four female pre
      pubertal rats were divided into control, DHEA and DHEA+Vit.D groups. In DHEA
      group, the PCOS rat model was developed by 6mg/kg/day dehydroepiandrosterone
      administration as subcutaneously injections. In DHEA+Vit.D group, 6 mg/kg/day
      DHEA and 120ng/100g/week 1,25(OH)2D3 was performed simultaneously. Controls were
      injected with vehicle alone. At the end of the 28 days, blood samples were
      collected and the ovarian tissues were taken for histological examinations.
      RESULTS: FSH, LH levels, LH/FSH ratio, and testosterone levels showed a
      significant increase in DHEA group when compared with the control group.
      Moreover, these measurements were lower in the treatment group than the DHEA
      group. In DHEA group, increased number of atretic follicles and cystic follicles
      were seen with light microscopic analysis. Cystic follicles with attenuated
      granulosa cell layers and thickened theca cell layers and lipid accumulation in
      interstitial cells were observed by electron microscope. It is observed that
      atretic and cystic follicles were decreased as a result of vitamin D treatment.
      CONCLUSION: Our results indicate the curative role of vitamin D treatment on the
      androgen excess in PCOS rat model which causes abnormalities in ovarian
      morphology and functions. Vitamin D has positive effects on the hormonal and
      structural changes observed in PCOS, but it has been concluded that long-term use
      may be more beneficial.

PMID- 29192812
TI  - Oxygen Prescription in Interstitial Lung Disease: 2.5 Billion Years in the
      Making.

PMID- 29192813
TI  - Yet Again, Air Pollution Impacts Lung Health.

PMID- 29192814
TI  - AnnalsATS 2022: Rigor, Value, Impact.

PMID- 29192816
TI  - Erratum: Care of the Critically Ill Burn Patient: An Overview from the
      Perspective of Optimizing Palliative Care.

PMID- 29192817
TI  - Can a Floppy Upper Airway Lead to Stiff Lungs?

PMID- 29192815
TI  - New Strategies and Challenges in Lung Proteomics and Metabolomics. An Official
      American Thoracic Society Workshop Report.
AB  - This document presents the proceedings from the workshop entitled, "New
      Strategies and Challenges in Lung Proteomics and Metabolomics" held February 4th
      5th, 2016, in Denver, Colorado. It was sponsored by the National Heart Lung Blood
      Institute, the American Thoracic Society, the Colorado Biological Mass
      Spectrometry Society, and National Jewish Health. The goal of this workshop was
      to convene, for the first time, relevant experts in lung proteomics and
      metabolomics to discuss and overcome specific challenges in these fields that are
      unique to the lung. The main objectives of this workshop were to identify,
      review, and/or understand: (1) emerging technologies in metabolomics and
      proteomics as applied to the study of the lung; (2) the unique composition and
      challenges of lung-specific biological specimens for metabolomic and proteomic
      analysis; (3) the diverse informatics approaches and databases unique to
      metabolomics and proteomics, with special emphasis on the lung; (4) integrative
      platforms across genetic and genomic databases that can be applied to lung
      related metabolomic and proteomic studies; and (5) the clinical applications of
      proteomics and metabolomics. The major findings and conclusions of this workshop
      are summarized at the end of the report, and outline the progress and challenges
      that face these rapidly advancing fields.

PMID- 29192819
TI  - Miliary Nodules: Not Always Tuberculosis.

PMID- 29192818
TI  - The Untold Toll of the Opioid Crisis on Intensive Care Units in the United
      States.

PMID- 29192820
TI  - An Unusual Headache in a Patient Treated with Continuous Positive Airway
      Pressure.

PMID- 29192821
TI  - Direct Connection: A Man with Lung Nodules and Filling Defects in the Pulmonary
      Arterial Tree.

PMID- 29192822
TI  - Unraveling the Cause of Severe Exertional Dyspnea in a Heavy Smoker.

PMID- 29192823
TI  - Incorporating Markers of Disease Severity into Near Real-Time Influenza
      Surveillance.

PMID- 29192824
TI  - Refractory Hypoxemia and Acute Respiratory Distress Syndrome Adjunctive
      Therapies: An Open Question?

PMID- 29192825
TI  - Procalcitonin in Chronic Obstructive Pulmonary Disease Exacerbations: Is It Ready
      for Primetime Use?

PMID- 29192826
TI  - Smokers Always Pay Twice.

PMID- 29192828
TI  - A Slippery Cause of a Slimy Problem: Mucin Induction by an Esterified Lipid.

PMID- 29192829
TI  - The Lung Likes the Little Fella miR-29.

PMID- 29192830
TI  - Hyaluronan: Local Climate Change in Asthma?

PMID- 29192831
TI  - Allergic Airway Disease: More than Meets the IgE?

PMID- 29192832
TI  - Hemoglobin alpha in Pulmonary Endothelium: Ironing Out Nitric Oxide Signaling.

PMID- 29192834
TI  - What Is Sepsis?

PMID- 29192833
TI  - Cytometric Gating Stringency Impacts Studies of Type 2 Innate Lymphoid Cells in
      Asthma.

PMID- 29192835
TI  - Recommendations for a Standardized Pulmonary Function Report. An Official
      American Thoracic Society Technical Statement.
AB  - BACKGROUND: The American Thoracic Society committee on Proficiency Standards for
      Pulmonary Function Laboratories has recognized the need for a standardized
      reporting format for pulmonary function tests. Although prior documents have
      offered guidance on the reporting of test data, there is considerable variability
      in how these results are presented to end users, leading to potential confusion
      and miscommunication. METHODS: A project task force, consisting of the committee
      as a whole, was approved to develop a new Technical Standard on reporting
      pulmonary function test results. Three working groups addressed the presentation
      format, the reference data supporting interpretation of results, and a system for
      grading quality of test efforts. Each group reviewed relevant literature and
      wrote drafts that were merged into the final document. RESULTS: This document
      presents a reporting format in test-specific units for spirometry, lung volumes,
      and diffusing capacity that can be assembled into a report appropriate for a
      laboratory's practice. Recommended reference sources are updated with data for
      spirometry and diffusing capacity published since prior documents. A grading
      system is presented to encourage uniformity in the important function of test
      quality assessment. CONCLUSIONS: The committee believes that wide adoption of
      these formats and their underlying principles by equipment manufacturers and
      pulmonary function laboratories can improve the interpretation, communication,
      and understanding of test results.

PMID- 29192836
TI  - Human Information Processing Shapes Language Change.
AB  - Human languages exhibit both striking diversity and abstract commonalities.
      Whether these commonalities are shaped by potentially universal principles of
      human information processing has been of central interest in the language and
      psychological sciences. Research has identified one such abstract property in the
      domain of word order: Although sentence word-order preferences vary across
      languages, the superficially different orders result in short grammatical
      dependencies between words. Because dependencies are easier to process when they
      are short rather than long, these findings raise the possibility that languages
      are shaped by biases of human information processing. In the current study, we
      directly tested the hypothesized causal link. We found that learners exposed to
      novel miniature artificial languages that had unnecessarily long dependencies did
      not follow the surface preference of their native language but rather
      systematically restructured the input to reduce dependency lengths. These results
      provide direct evidence for a causal link between processing preferences in
      individual speakers and patterns in linguistic diversity.

PMID- 29192837
TI  - Effects of the Nordic Hamstring exercise on sprint capacity in male football
      players: a randomized controlled trial.
AB  - : This assessor-blinded, randomized controlled superiority trial investigated the
      efficacy of the 10-week Nordic Hamstring exercise (NHE) protocol on sprint
      performance in football players. Thirty-five amateur male players (age: 17-26
      years) were randomized to a do-as-usual control group (CG; n = 17) or to 10-weeks
      of supervised strength training using the NHE in-season (IG; n = 18). A repeated
      sprint test, consisting of 4 * 6 10 m sprints, with 15 s recovery period between
      sprints and 180 s between sets, was conducted to evaluate total sprint time as
      the primary outcome. Secondary outcomes were best 10 m sprint time (10mST) and
      sprint time during the last sprint (L10mST). Additionally, peak eccentric
      hamstring strength (ECC-PHS) and eccentric hamstring strength capacity (ECC
      CAPHS) were measured during the NHE. Ten players were lost to follow-up, thus 25
      players were analyzed (CG n = 14; IG n = 11). Between-group differences in mean
      changes were observed in favor of the IG for sprint performance outcomes; TST (
      0.649 s, p = 0.056, d = 0.38), 10mST (-0.047 s, p = 0.005, d = 0.64) and L10mST (
      0.052 s, p = 0.094, d = 0.59), and for strength outcomes; ECC-PHS (62.3 N, p =
      0.006, d = 0.92), and ECC-CAPHS (951 N, p = 0.005, d = 0.95). In conclusion, the
      NHE showed small-to-medium improvements in sprint performance and large increases
      in peak eccentric hamstring strength and capacity. TRIAL REGISTRATION NUMBER:
      NCT02674919.

PMID- 29192838
TI  - Perceived life stress and anxiety correlate with chronic gastrointestinal
      symptoms in runners.
AB  - Numerous causes of exercise-related gastrointestinal (GI) distress exist but
      scarce research has evaluated potential psychological causes. Runners (74 men, 76
      women) prospectively recorded running duration, intensity (Rating of Perceived
      Exertion [RPE]), and GI symptoms for 30 days. Six GI symptoms were rated on a 0
      10 scale. The percentage of runs over 30 days that participants reported at least
      one upper, lower, or any GI symptom >=3 was calculated. After 30 days,
      participants completed a questionnaire on GI distress triggers (demographics,
      anthropometrics, experience, analgesic use, antibiotic use, probiotic
      consumption, fluid/food intake, stress, anxiety). Stress and anxiety were
      measured via the Perceived Stress Scale (PSS) and Beck Anxiety Inventory (BAI).
      The median percentage of runs that participants experienced at least one GI
      symptom >=3 was 45.6% (interquartile range [IQR], 16.6-67.3%). Age and running
      experience negatively correlated with GI distress occurrence (rho = -0.17 to 
      0.34; p < 0.05). Run RPE, probiotic food consumption, PSS scores, and BAI scores
      positively correlated with GI distress occurrence (rho = 0.18 to 0.36; p < 0.05).
      Associations between GI distress, stress and anxiety remained significant after
      adjustment for covariates, except for lower GI symptoms. This study suggests that
      stress and anxiety contribute to running-related GI distress.

PMID- 29192839
TI  - Telephone helplines as a source of support for eating disorders: Service user,
      carer, and health professional perspectives.
AB  - Access to care for eating disorders can be problematic for numerous reasons
      including lack of understanding and delays with treatment referrals. Previous
      research has highlighted the benefits of telephone helplines as an accessible
      source of support for those who may not wish to access face-to-face support or to
      fill a gap for those waiting for treatment. This study aimed to gain an insight
      into the perspectives of those who may use or refer others to a telephone
      helpline in order to identify the requirements of such a service. Triangulation
      of service user, carer and health professionals' perspectives resulted in
      identification of themes relating to the type of support, delivery and
      practicalities of a helpline. The findings indicated that telephone helplines may
      offer numerous benefits for individuals with an eating disorder, whether accessed
      as a first step, alongside treatment or as an extension of this support when in
      recovery. Additionally helplines may provide an opportunity for carers to access
      information and discuss their own experiences, while supporting their loved one.
      Raising awareness of these services is important to encourage those affected by
      an eating disorder to access and make the most of this type of support. These
      findings offer an insight into the key requirements for new and existing service
      development with regard to both the type of support and the method of
      communication required by individuals with eating disorders.

PMID- 29192840
TI  - Betulinic acid induces apoptosis and ultrastructural changes in MDA-MB-231 breast
      cancer cells.
AB  - The aim of this study is to investigate the effects of betulinic acid (BA) on
      triple-negative breast cancer MDA-MB-231 cells and observe the ultrastructural
      changes. The concentration of BA required to induce apoptosis in MDA-MB-231 cells
      has been previously reported. In this study, a cell counting kit-8 proliferation
      assay was used to measure cell viability and the apoptosis rate. Western blotting
      was performed to observe the protein expression levels of Bcl-2. Cell morphology
      and changes in cell density were observed by microscopy. Electron microscopy
      revealed pyknotic nuclei as well as vacuoles. Collectively, our results showed
      the morphological mechanisms by which BA impairs the ultrastructure of MDA-MB-231
      cells.

PMID- 29192841
TI  - A Type 3 Prophage of 'Candidatus Liberibacter asiaticus' Carrying a Restriction
      Modification System.
AB  - Prophages, the lysogenic form of bacterial phages, are important genetic entities
      of 'Candidatus Liberibacter asiaticus' (CLas), a nonculturable alpha
      proteobacterium associated with citrus Huanglongbing. Two CLas prophages have
      been described, SC1 (NC_019549.1, Type 1) and SC2 (NC_019550.1, Type 2), which
      involve the lytic cycle and the lysogenic cycle, respectively. To explore the
      prophage repertoire, 523 CLas DNA samples extracted from leaf petioles of CLas
      infected citrus were collected from southern China and surveyed for Type 1 and
      Type 2 prophages by specific PCR. Eighteen samples were found lacking both
      prophages. One sample, JXGC, sequenced using Illumina HiSeq, generated >100
      million short sequence reads (150 bp per read). Read mapping to known prophage
      sequences showed a sequence coverage of 46% to SC1 and 50% to SC2. BLAST search
      using SC1 and SC2 as queries identified three contigs from the JXGC de novo
      assembly that form a circular P-JXGC-3 (31,449 bp), designated as a new Type 3
      prophage. Chromosomal integration of P-JXGC-3 was detected to occur within a
      helicase gene, resulting in a duplication of this gene. P-JXGC-3 had 36 open
      reading frames (ORFs), 10 of which were not found in Type 1 or Type 2 prophages,
      including four genes that encoded a restriction-modification (R-M) system (hsdR,
      hsdS, hsdM1, and hsdM2). Typed by prophage-specific PCR, the CLas strains in
      southern China contained all combinations of the three prophage types with the
      exception of a Type 2-Type 3 combination, suggesting active ongoing prophage
      phage interactions. Based on gene annotation, P-JXGC-3 is not capable of
      reproduction via the lytic cycle. The R-M system was speculated to play a role
      against Type 1 prophage-phage invasion.

PMID- 29192842
TI  - Validity of an ultra-wideband local positioning system to measure locomotion in
      indoor sports.
AB  - The validity of an Ultra-wideband (UWB) positioning system was investigated
      during linear and change-of-direction (COD) running drills. Six recreationally
      active men performed ten repetitions of four activities (walking, jogging,
      maximal acceleration, and 45o COD) on an indoor court. Activities were repeated
      twice, in the centre of the court and on the side. Participants wore a receiver
      tag (Clearsky T6, Catapult Sports) and two reflective markers placed on the tag
      to allow for comparisons with the criterion system (Vicon). Distance, mean and
      peak velocity, acceleration, and deceleration were assessed. Validity was
      assessed via percentage least-square means difference (Clearsky-Vicon) with 90%
      confidence interval and magnitude-based inference; typical error was expressed as
      within-subject standard deviation. The mean differences for distance, mean/peak
      speed, and mean/peak accelerations in the linear drills were in the range of 0.2
      12%, with typical errors between 1.2 and 9.3%. Mean and peak deceleration had
      larger differences and errors between systems. In the COD drill, moderate-to
      large differences were detected for the activity performed in the centre of the
      court, increasing to large/very large on the side. When filtered and smoothed
      following a similar process, the UWB-based positioning system had acceptable
      validity, compared to Vicon, to assess movements representative of indoor sports.

PMID- 29192844
TI  - Resveratrol reduces light and electron microscopic changes in acetaminophen
      induced hepatotoxicity in rats: Role of iNOS expression.
AB  - INTRODUCTION: Hepatotoxicity is a major complication of acetaminophen (APAP), a
      widely used analgesic and antipyretic drug. Resveratrol (RSV) is a naturally
      occurring diphenol and it has anticancer, antioxidant, and anti-inflammatory
      properties. OBJECTIVES: In this study, the beneficial effects of RSV on APAP
      induced hepatotoxicity was investigated in rats. MATERIALS AND METHODS: Group 1:
      Ethanol, Group 2: Saline, Group 3: RSV (10 mg/kg/ip), Group 4: APAP (1000
      mg/kg/ip/single dose), Group 5: APAP+RSV (20 min after administration of APAP).
      The rats were sacrificed 24 h after administration of APAP. Light and electron
      microscopic changes were evaluated. Levels of malondialdehyde (MDA) and
      glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities were
      determined in liver tissue. RESULTS: Rats of the ethanol, saline, and RSV groups
      did not present any histopathological alterations. In the APAP group, we observed
      vascular congestion, necrosis, inflammation, sinusoidal dilatation, and loss of
      glycogen content. In the APAP+RSV group, these changes were markedly reduced.
      iNOS immunostaining showed very weak positive stained hepatocytes the sections of
      control, saline, and RSV groups. However, in the APAP group, iNOS immunostaining
      was most evident in pericentral hepatocytes. In the same areas in APAP+RSV group,
      intensity of iNOS immunostaining decreased. A significant increase in MDA and
      decreases in GSH level, CAT, and SOD activity indicated that APAP-induced
      hepatotoxicity was mediated through oxidative stress. Significant beneficial
      changes were noted in tissue oxidative stress indicators in rats treated with
      RSV. CONCLUSION: These biochemical, histopathological, and ultrastructural
      findings revealed that RSV reduced the severity of APAP-induced alterations in
      liver.

PMID- 29192843
TI  - Somatostatin in Alzheimer's disease: A new Role for an Old Player.
AB  - The amyloid beta (Abeta) peptide is central to the pathogenesis of Alzheimer's
      disease (AD). Insights into Abeta-interacting proteins are critical for
      understanding the molecular mechanisms underlying Abeta-mediated toxicity. We
      recently undertook an in-depth in vitro interrogation of the Abeta1-42
      interactome using human frontal lobes as the biological source material and
      taking advantage of advances in mass spectrometry performance characteristics.
      These analyses uncovered the small cyclic neuropeptide somatostatin (SST) to be
      the most selectively enriched binder to oligomeric Abeta1-42. Subsequent
      validation experiments revealed that SST interferes with Abeta fibrillization and
      promotes the formation of Abeta assemblies characterized by a 50-60 kDa SDS
      resistant core. The distributions of SST and Abeta overlap in the brain and SST
      has been linked to AD by several additional observations. This perspective
      summarizes this body of literature and draws attention to the fact that SST is
      one of several neuropeptide hormones that acquire amyloid properties before their
      synaptic release. The latter places the interaction between SST and Abeta among
      an increasing number of observations that attest to the ability of amyloidogenic
      proteins to influence each other. A model is presented which attempts to
      reconcile existing data on the involvement of SST in the AD etiology.

PMID- 29192845
TI  - Systematic alteration of apoptosis: a review with ultrastructural observations on
      leukemia cells in vivo.
AB  - The ultrastructural characteristics of apoptosis have been described
      microscopically for four decades. Alterations of nuclei, apoptotic bodies,
      cytoplasm, and some organelles have been illustrated and investigated during
      apoptosis. The successive changes of cellular components corresponding with
      differentiation of apoptotic cells are illustrated in the present review, based
      on ultrastructural observation of leukemia cells of patients in our routine
      clinic work by transmission electron microscopy. Most electron micrographs
      demonstrated that membranous components of nuclear envelop, rough endoplasmic
      reticulum and Golgi apparatus, and mitochondria were degenerated step by step
      during apoptosis. The successive images suggested that the endoplasmic reticulum
      and Golgi apparatus were transferred to cell surface from cytoplasm and
      participated in formation of apoptotic bodies in apoptosis, although relevant
      clinical data and more experimental evidence were needed for restraining of
      leukemia cases from diagnostic work randomly in recent decades.

PMID- 29192846
TI  - A cross-sectional and prospective analyse of reallocating sedentary time to
      physical activity on children's cardiorespiratory fitness.
AB  - Cardiorespiratory fitness (CRF) is associated with health benefits in children,
      improving cardiac morphology, cardiovascular disease risk factors, and biological
      outcomes. This study aimed to examine the substitution effects of displaying a
      fixed duration of sedentary time with a fixed duration of physical activity (PA)
      at different intensities on children's CRF. A total of 315 children (136 boys)
      were assessed (age: 10.6 +/- 0.6 years old). Outcomes at baseline and follow-up
      (16-months) were CRF determined using a maximal cycle test and sedentary time and
      PA measured with accelerometers. Data were analysed by isotemporal substitution
      analyses estimating the effect of reallocating 30 min/day of sedentary time by
      light (LPA), moderate (MPA) and vigorous physical activity (VPA) on CRF. VPA was
      positively and significantly associated with CRF cross-sectional (beta = 0.026, p
      < 0.001) and prospectively (beta = 0.010, p < 0.001). Reallocating 30 min/day of
      sedentary time into VPA was positively cross-sectionally (beta = 0.780, p <
      0.001) and prospectively (beta = 0.303, p < 0.05) associated with CRF.
      Conversely, relocating 30-minutes of sedentary time into 30 minutes of LPA and
      MPA was not associated with CRF. These results suggest that reallocating an equal
      amount of time from sedentary into VPA is cross-sectional and prospectively
      associated with a favourable CRF.

PMID- 29192847
TI  - Acid-etching technique of non-decalcified bone samples for visualizing osteocyte
      lacuno-canalicular network using scanning electron microscope.
AB  - The aim of this study was to define the acid-etching technique for bone samples
      embedded in polymethyl metacrylate (PMMA) in order to visualize the osteocyte
      lacuno-canalicular network (LCN) for scanning electron microscopy (SEM). Human
      jaw bone tissue samples (N = 18) were collected from the study population
      consisting of patients having received dental implant surgery. After collection,
      the bone samples were fixed in 70% ethanol and non-decalcified samples embedded
      routinely into polymethyl metacrylate (PMMA). The PMMA embedded specimens were
      acid-etched in either 9 or 37% phosphoric acid (PA) and prepared for SEM for
      further analysis. PMMA embedded bone specimens acid-etched by 9% PA concentration
      accomplishes the most informative and favorable visualization of the LCN to be
      observed by SEM. Etching of PMMA embedded specimens is recommendable to start
      with 30 s or 40 s etching duration in order to find the proper etching duration
      for the samples examined. Visualizing osteocytes and LCN provides a tool to study
      bone structure that reflects changes in bone metabolism and diseases related to
      bone tissue. By proper etching protocol of non-decalcified and using scanning
      electron microscope it is possible to visualize the morphology of osteocytes and
      the network supporting vitality of bone tissue.

PMID- 29192850
TI  - Effect Size and Clinical Significance.

PMID- 29192848
TI  - Effects of resveratrol on high-fructose-induced testis injury in rats.
AB  - This study investigated whether a high-fructose (HFr) diet changes the morphology
      of seminiferous tubules (ST) in rats and resveratrol (RES) has a possible
      restoring effect in this sense. Fructose (30%; w/v) was administered to rats
      alone or together with RES (50 mg/L) in drinking water for 8 weeks. In the HFr
      group, destruction of the germinal epithelium led to the detection of immature
      germ cells in the lumen. HFr diet gave rise to a decrease in the ST diameters (p
      < 0.05), Johnsen's tubular biopsy score values (p < 0.001), and an increase in
      the apoptotic index (p < 0.05). Ultrastructurally, HFr feeding increased lipid
      accumulation (p < 0.01), mitochondrial damage, and acrosomal abnormalities in
      spermatogenic cells. Treatment of HFr -fed rats with RES improved the reduced ST
      diameters and overall general histological and ultrastructural abnormalities of
      the STs, but did not change the increased apoptotic index.

PMID- 29192851
TI  - In Reference to: "Can Intracapsular Tonsillectomy Be an Alternative to Classical
      Tonsillectomy? A Meta-analysis".

PMID- 29192852
TI  - The P Value Problem in Otolaryngology: Shifting to Effect Sizes and Confidence
      Intervals.

PMID- 29192854
TI  - Null Hypotheses, Interval Estimation, and Bayesian Analysis.
AB  - Hypothesis testing using a frequentist approach is the mainstay of biostatistics
      and forms the foundation for assessing the significance of study results. This
      classical method has well-understood advantages as it determines whether data are
      statistically improbable and provides a threshold (ie, the P value) for
      delineating significance. Alternative statistical approaches have been proposed,
      including Bayesian analysis. This technique incorporates a prior probability as
      to what is already known clinically with the observed data. It is important for
      otolaryngologists to understand the advantages and disadvantages of these 2
      approaches to conduct the most appropriate analyses.

PMID- 29192853
TI  - To P or Not to P: Backing Bayesian Statistics.
AB  - In biomedical research, it is imperative to differentiate chance variation from
      truth before we generalize what we see in a sample of subjects to the wider
      population. For decades, we have relied on null hypothesis significance testing,
      where we calculate P values for our data to decide whether to reject a null
      hypothesis. This methodology is subject to substantial misinterpretation and
      errant conclusions. Instead of working backward by calculating the probability of
      our data if the null hypothesis were true, Bayesian statistics allow us instead
      to work forward, calculating the probability of our hypothesis given the
      available data. This methodology gives us a mathematical means of incorporating
      our "prior probabilities" from previous study data (if any) to produce new
      "posterior probabilities." Bayesian statistics tell us how confidently we should
      believe what we believe. It is time to embrace and encourage their use in our
      otolaryngology research.

PMID- 29192855
TI  - Early outcomes after intrathecal baclofen therapy in ambulatory patients with
      multiple sclerosis.
AB  - OBJECTIVE: Multiple sclerosis (MS) is a chronic autoimmune disease that causes
      demyelination and axonal loss. Walking difficulties are a common and debilitating
      symptom of MS; they are usually caused by spastic paresis of the lower
      extremities. Although intrathecal baclofen (ITB) therapy has been reported to be
      an effective treatment for spasticity in MS, there is limited published evidence
      regarding its effects on ambulation. The goal of this study was to characterize
      ITB therapy outcomes in ambulatory patients with MS. METHODS: Data from 47
      ambulatory patients with MS who received ITB therapy were analyzed
      retrospectively. Outcome measures included Modified Ashworth Scale, Spasm
      Frequency Scale, Numeric Pain Rating Scale, and the Timed 25-Foot Walk. Repeated
      measures ANOVA was used to test for changes in outcome measures between baseline
      and posttreatment (6 months and 1 year). Significance was set at p < 0.05.
      Descriptive data are expressed as the mean +/- SD, and results of the repeated
      measures ANOVA tests and the Wilcoxon rank-sum test are expressed as the mean +/-
      SEM. RESULTS: There was a statistically significant reduction in the following
      variables: 1) aggregate lower-extremity Modified Ashworth Scale scores (from 14.8
      +/- 1.0 before ITB therapy to 5.8 +/- 0.8 at 6 months posttreatment and 6.4 +/-
      0.9 at 1 year [p < 0.05]); 2) Numeric Pain Rating Scale scores (4.4 +/- 0.5
      before ITB, 2.8 +/- 0.5 at 6 months, and 2.4 +/- 0.4 at 1 year [p < 0.05]); 3)
      spasm frequency (45.7% of the patients reported a spasm frequency of >= 1 event
      per hour before ITB therapy, whereas 15.6% and 4.3% of the patients reported the
      same at 6 months and 1 year posttreatment, respectively [p < 0.05]); and 4) the
      number of oral medications taken for spasticity (p < 0.05). Of the 47 patients,
      34 remained ambulatory at 6 months, and 32 at 1 year posttreatment. There was no
      statistically significant change in performance on the Timed 25-Foot Walk test
      over time for those patients who remained ambulatory. CONCLUSIONS: In this
      retrospective study, the authors found that ITB therapy is effective in reducing
      spasticity and related symptoms in ambulatory patients with MS. Because the use
      of ITB therapy is increasing in ambulatory patients with MS, randomized,
      prospective studies are important to help provide a more useful characterization
      of the effects of ITB therapy on ambulation.

PMID- 29192856
TI  - Management of antiplatelet therapy in patients undergoing neuroendovascular
      procedures.
AB  - Neuroendovascular techniques for treating cerebral aneurysms and other
      cerebrovascular pathology are increasingly becoming the standard of care.
      Intraluminal stents, aneurysm coils, and other flow diversion devices typically
      require concomitant antiplatelet therapy to reduce thromboembolic complications.
      The variability inherent with the pharmacodynamic response to common antiplatelet
      agents such as aspirin and clopidogrel complicates optimal selection of
      antiplatelet agents by clinicians. This review serves to discuss the literature
      related to antiplatelet use in neuroendovascular procedures and provides
      recommendations for clinicians on how to approach patients with variable response
      to antiplatelet agents, particularly clopidogrel.

PMID- 29192857
TI  - Knowledge silos: assessing knowledge sharing between specialties through the
      vestibular schwannoma literature.
AB  - OBJECTIVE It is common for a medical disorder to be managed or researched by
      individuals who work within different specialties. It is known that both
      neurosurgeons and neurotologists manage vestibular schwannoma (VS) patients.
      While overlap in specialty focus has the potential to stimulate multidisciplinary
      collaboration and innovative thinking, there is a risk of specialties forming
      closed-communication loops, called knowledge silos, which may inhibit knowledge
      diffusion. This study quantitatively assessed knowledge sharing between
      neurosurgery and otolaryngology on the subject of VS. METHODS A broad Web of
      Science search was used to download details for 4439 articles related to VS
      through 2016. The publishing journal's specialty and the authors' specialties
      (based on author department) were determined for available articles. All 114,647
      of the article references were categorized by journal specialty. The prevalence
      of several VS topics was assessed using keyword searches of titles. RESULTS For
      articles written by neurosurgeons, 44.0% of citations were from neurosurgery
      journal articles and 23.4% were from otolaryngology journals. The citations of
      otolaryngology authors included 11.6% neurosurgery journals and 56.5%
      otolaryngology journals. Both author specialty and journal specialty led to more
      citations of the same specialty, though author specialty had the largest effect.
      Comparing the specialties' literature, several VS topics had significantly
      different levels of coverage, including radiosurgery and hearing topics. Despite
      the availability of the Internet, there has been no change in the proportions of
      references for either specialty since 1997 (the year PubMed became publicly
      available). CONCLUSIONS Partial knowledge silos are observed between neurosurgery
      and otolaryngology on the topic of VS, based on the peer-reviewed literature. The
      increase in access provided by the Internet and searchable online databases has
      not decreased specialty reference bias. These findings offer lessons to improve
      cross-specialty collaboration, physician learning, and consensus building.

PMID- 29192858
TI  - Head-up display may facilitate safe keyhole surgery for cerebral aneurysm
      clipping.
AB  - OBJECTIVE: The head-up display (HUD) is a modern technology that projects images
      or numeric information directly into the observer's sight line. Surgeons will no
      longer need to look away from the surgical view using the HUD system to confirm
      the preoperative or navigation image. The present study investigated the
      usefulness of the HUD system for performing cerebral aneurysm clipping surgeries.
      METHODS: Thirty-five patients underwent clipping surgery, including 20 keyhole
      surgeries for unruptured cerebral aneurysm, using the HUD system. Image
      information of structures such as the skull, cerebral vasculature, and aneurysm
      was integrated by the navigation software and linked with the positional
      coordinates of the microscope field of view. "Image injection" allowed
      visualization of the main structures that were concurrently tracked by the
      navigation image, and "closed shutter" switched the microscope field of view and
      the pointer image of the 3D brain image. RESULTS: The HUD system was effective
      for estimating the location and 3D anatomy of the aneurysm before craniotomy or
      dural opening in most patients. Scheduled keyhole minicraniotomy and opening of
      the sylvian fissure or partial rectal gyrus resection were performed on the
      optimized location with a minimum size in 20 patients. CONCLUSIONS: The HUD
      images superimposed on the microscope field of view were remarkably useful for
      less invasive and more safe aneurysm clipping and, in particular, keyhole
      clipping.

PMID- 29192859
TI  - Chemical venous thromboembolism prophylaxis in neurosurgical patients: an updated
      systematic review and meta-analysis.
AB  - OBJECTIVE: Venous thromboembolism (VTE) is a common and potentially life
      threatening complication. The risk of serious hemorrhagic complications when
      starting chemical prophylaxis for VTE prevention is a substantial concern for
      neurosurgeons. The objective of this study was to perform an updated systematic
      review and meta-analysis to determine if the rates of VTE and bleeding
      complications are different in patients undergoing chemoprophylaxis compared with
      placebo or mechanical prophylaxis alone following cranial or spinal procedures.
      METHODS: In February 2016 a systematic literature review was performed
      identifying 3944 articles from 4 different databases. A random-effects meta
      analysis was performed after identifying the articles that met inclusion
      criteria. RESULTS: Nine articles that met the inclusion criteria were included.
      The quality of the studies was good, with all of them being classified as Level 2
      evidence, with moderate Jadad scores. A meta-analysis comparing chemoprophylaxis
      with placebo in the prevention of deep venous thrombosis showed a significant
      benefit to chemical prophylaxis (OR 0.51, 95% CI 0.37-0.71; p < 0.0001). No
      significant increase in major intracranial hemorrhage (p = 0.60), major
      extracranial hemorrhage (p = 0.98), or minor bleeding complications (p = 0.60)
      was found. CONCLUSIONS: Based on moderate-to-good quality of evidence,
      chemoprophylaxis is beneficial in preventing VTE, with no significant increase in
      either major or minor bleeding complications in patients undergoing cranial and
      spinal procedures. Further research is needed to determine whether this
      conclusion holds true for more specific subpopulations.

PMID- 29192860
TI  - Delayed cyst formation after stereotactic radiosurgery for brain arteriovenous
      malformations.
AB  - OBJECTIVE: Stereotactic radiosurgery (SRS) is a commonly employed treatment
      modality for brain arteriovenous malformations (AVMs). However, due to the low
      frequency of delayed cyst formation after AVM SRS, as well as the prolonged time
      interval between treatment and its occurrence, the characteristics of post-SRS
      cyst formation are not well defined. Therefore, the aims of this retrospective
      cohort study are to determine the rate of cyst formation after SRS for AVMs,
      identify predictive factors, and evaluate the clinical sequelae of post-SRS
      cysts. METHODS: The authors analyzed an SRS database for AVM patients who
      underwent SRS at the University of Virginia and identified those who developed
      post-SRS cysts. Statistical analyses were performed to determine predictors of
      post-SRS cyst formation and the effect of cyst formation on new or worsening
      seizures after SRS. RESULTS: The study cohort comprised 1159 AVM patients treated
      with SRS; cyst formation occurred in 17 patients (post-SRS cyst rate of 1.5%).
      Compared with patients who did not develop post-SRS cysts, those with cyst
      formation were treated with a greater number of radiosurgical isocenters (mean
      3.8 vs 2.8, p = 0.047), had a longer follow-up (mean 132 vs 71 months, p <
      0.001), were more likely to develop radiological radiation-induced changes (RIC)
      (64.7% vs 36.1%, p = 0.021), and had a longer duration of RIC (57 vs 21 months, p
      < 0.001). A higher number of isocenters (p = 0.014), radiological RIC (p =
      0.002), and longer follow-up (p = 0.034) were found to be independent predictors
      of post-SRS cyst formation in the multivariate analysis. There was a trend toward
      a significant association between cyst formation and new or worsening seizures in
      univariate analysis (p = 0.054). CONCLUSIONS: Patients with greater nidal
      complexity appear to be more prone to post-SRS cyst formation. The findings of
      this study emphasize the importance of long-term follow-up for patients who have
      undergone AVM SRS, even after nidal obliteration is achieved. Post-SRS cysts may
      be epileptogenic, although seizure outcomes after AVM SRS are multifactorial.

PMID- 29192861
TI  - Ectopic brain tissue in the trigeminal nerve presenting as rapid-onset trigeminal
      neuralgia: case report.
AB  - The authors report the case of a 52-year-old man who presented with rapid-onset
      lancinating facial pain consistent with trigeminal neuralgia. Magnetic resonance
      imaging revealed a nonenhancing small lesion on the right trigeminal nerve
      concerning for an atypical schwannoma or neuroma. The patient underwent resection
      of the mass via a right retrosigmoid approach. His facial pain completely
      resolved immediately postoperatively and had not recurred at 6 months after
      surgery. The mass was consistent with normal brain tissue (neurons and glial
      cells) without evidence of mitoses. A final histopathological diagnosis of
      ectopic brain tissue with neural tissue demonstrating focal, chronic T-cell
      inflammation was made. The partial rhizotomy during resection was curative for
      the facial pain. To the authors' knowledge, this is the first report of
      neuroglial ectopia causing trigeminal neuralgia.

PMID- 29192862
TI  - Clinicoradiological features of intraneural perineuriomas obviate the need for
      tissue diagnosis.
AB  - OBJECTIVE: This study aimed to define a set of clinicoradiological parameters
      with a high specificity for the diagnosis of intraneural perineurioma, obviating
      the need for operative tissue diagnosis. METHODS: The authors retrospectively
      reviewed MR images obtained in a large cohort of patients who underwent targeted
      fascicular biopsy and included only those patients for whom the biopsy yielded a
      diagnosis. Clinical and radiological findings were then tested for their ability
      to predict a tissue diagnosis of intraneural perineurioma. The authors propose a
      new set of diagnostic criteria, referred to as the Perineurioma Diagnostic
      Criteria. The sensitivity, specificity, positive predictive value, and negative
      predictive value of several clinicoradiological methods of diagnosis were
      compared. RESULTS: A total of 195 patients who underwent targeted fascicular
      biopsy were included in the cohort, of whom 51 had a tissue diagnosis of
      intraneural perineurioma. When the clinicoradiological methods used in this study
      were compared, the highest sensitivity (0.86), negative predictive value (0.95),
      and F1 score (0.88) were observed for the decision trees generated in C5.0 and
      rPart, whereas the highest specificity (1.0) and positive predictive value (1.0)
      were observed for the Perineurioma Diagnostic Criteria. CONCLUSIONS: This study
      identified clinical and radiological features that are associated with a
      diagnosis of perineurioma. The Perineurioma Diagnostic Criteria were determined
      to be the following: 1) no cancer history, 2) unifocal disease, 3) moderate to
      severe hyperintensity on T2-weighted MR images, 4) moderate to severe contrast
      enhancement, 5) homogeneous contrast enhancement, 6) fusiform shape, 7)
      enlargement of the involved nerves, and 8) age <= 40 years. Use of the
      Perineurioma Diagnostic Criteria obviates the need for tissue diagnosis when all
      of the criteria are satisfied.

PMID- 29192864
TI  - Letter to the Editor. Usefulness of 5-ALA in resection of intracranial
      meningiomas.

PMID- 29192863
TI  - Precipitating hydrophobic injectable liquid embolization of intracranial vascular
      shunts: initial experience and technical note.
AB  - Precipitating hydrophobic injectable liquid (PHIL) is a newly available liquid
      embolic agent for endovascular therapy. It is nonadhesive and composed of a
      biocompatible polymer dissolved in dimethyl sulfoxide solvent and bonded
      covalently with iodine. In this report, the authors present their preliminary
      experience using PHIL in the treatment of intracranial vascular shunts. Between
      July 2015 and December 2015, 11 patients underwent endovascular embolization
      using the PHIL embolic agent. Five patients had arteriovenous malformations, 4
      had dural arteriovenous fistulas, 1 patient had a carotid-cavernous fistula, and
      1 patient had a pial arteriovenous fistula. Clinical features, angioarchitectural
      characteristics, procedural details, and periprocedural complications were
      included in the analysis. Complete or near-complete obliteration of the nidus or
      fistulas was achieved in 8 of these patients. Partial embolization (approximately
      80% in 2 and 30% in 1) was attained in the other 3 patients. Satisfactory venous
      penetration after nidal embolization was achieved in all patients. In 1 patient,
      the microcatheter could not be retrieved. No other major complications related to
      PHIL injection were noted during the procedure or periprocedural period. Clinical
      follow-up ranging from 8 months to 1 year showed good outcomes in all but 1
      patient, who experienced an intraventricular hemorrhage 6 weeks after
      embolization. PHIL appears to be an effective alternative embolic material with
      certain advantages over other available liquid embolic agents. Further studies
      with adequate follow-up are required to fully evaluate its safety and efficacy.

PMID- 29192865
TI  - Electrocorticography and the early maturation of high-frequency suppression
      within the default mode network.
AB  - OBJECTIVE The acquisition and refinement of cognitive and behavioral skills
      during development is associated with the maturation of various brain oscillatory
      activities. Most developmental investigations have identified distinct patterns
      of low-frequency electrophysiological activity that are characteristic of various
      behavioral milestones. In this investigation, the authors focused on the cross
      sectional developmental properties of high-frequency spectral power from the
      brain's default mode network (DMN) during goal-directed behavior. METHODS The
      authors contrasted regionally specific, time-evolving high gamma power (HGP) in
      the lateral DMN cortex between 3 young children (age range 3-6 years) and 3
      adults by use of electrocorticography (ECoG) recordings over the left perisylvian
      cortex during a picture-naming task. RESULTS Across all participants, a nearly
      identical and consistent response suppression of HGP, which is a functional
      signature of the DMN, was observed during task performance recordings acquired
      from ECoG electrodes placed over the lateral DMN cortex. This finding provides
      evidence of relatively early maturation of the DMN. Furthermore, only HGP
      relative to evoked alpha and beta band power showed this level of consistency
      across all participants. CONCLUSIONS Regionally specific, task-evoked suppression
      of the high-frequency components of the cortical power spectrum is established
      early in brain development, and this response may reflect the early maturation of
      specific cognitive and/or computational mechanisms.

PMID- 29192866
TI  - Frontoethmoidal meningoencephalocele: appraisal of a craniofacial surgical
      teaching program in Cambodia.
AB  - OBJECTIVE The treatment of frontoethmoidal meningoencephaloceles (fMECs) in
      Cambodia was not possible before the development of a program that taught some
      Khmer surgeons (working at the Children's Surgical Centre in Phnom Penh) how to
      surgically correct these deformities without any foreign help. The results of
      that teaching program are discussed in this paper. METHODS Between 2004 and 2009,
      both local and visiting foreign neurosurgical and craniofacial surgeons (the
      visitors coming twice a year) worked together to operate on 200 patients, and a
      report on those cases was published in 2010. In subsequent years (2010-2016), the
      Khmer surgeons operated on 100 patients without the presence of the visiting
      surgeons. In this study, the authors compare the second case series with the
      previously published series and the literature in terms of results and
      complications. The operations were performed with limited surgical materials and
      equipment, using a combined bicoronal and transfacial approach in most cases.
      Most of the patients came from very poor families. RESULTS Organizing the
      postoperative follow-up of these low-income patients (mean age 12 years) was
      probably the most challenging part of this teaching program. Nine of the patients
      were lost to surgical follow-up. In the other cases, cosmetic results were judged
      by the surgeons as worse than the patient's preoperative appearance in 1 case,
      poor in 12 cases, average in 27, and good in 51-data that are significantly less
      encouraging than the results reported by the joint local/visiting teams in 2010
      (p = 0.0001). Nevertheless, patients and parents tended to have a better overall
      opinion about the surgical results (rating the results as good in 84% of the 80
      cases in which parent or patient ratings were available). Twenty postoperative
      complications were observed (the most common being temporary CSF leaks). The rate
      of immediate postoperative complications directly related to fMEC surgery was
      less than that in the previous series, but the difference was not statistically
      significant (20% vs 28.5%, p = 0.58). No death was noted in this case series (in
      contrast to the previous series). Social questionnaire results confirmed that
      fMEC correction partially improved the adverse social and educational
      consequences of fMEC in affected children. CONCLUSIONS In the current state of
      this program, the local surgeons are able to correct fMECs in their own country,
      without foreign assistance, with good results in a majority of patients. Such
      humanitarian teaching programs generally take years to achieve the initial aims.

PMID- 29192867
TI  - Reduction of hyperthermia in pediatric patients with severe traumatic brain
      injury: a quality improvement initiative.
AB  - OBJECTIVE Severe traumatic brain injury remains a leading cause of morbidity and
      mortality in the pediatric population. Providers focus on reducing secondary
      brain injury by avoiding hypoxemia, avoiding hypotension, providing
      normoventilation, treating intracranial hypertension, and reducing cerebral
      metabolic demand. Hyperthermia is frequently present in patients with severe
      traumatic brain injury, contributes to cerebral metabolic demand, and is
      associated with prolonged hospital admission as well as impaired neurological
      outcome. The objective of this quality improvement initiative was to reduce the
      duration of hyperthermia for pediatric patients with severe traumatic brain
      injury during the initial 72 hours of admission to the pediatric intensive care
      unit. METHODS A retrospective chart review was performed to evaluate the
      incidence and duration of hyperthermia within a preintervention cohort. The
      retrospective phase was followed by three 6-month intervention periods
      (intervention Phase 1, the maintenance phase, and intervention Phase 2).
      Intervention Phase 1 entailed placement of a cooling blanket on the bed prior to
      patient arrival and turning it on once the patient's temperature rose above
      normothermia. The maintenance phase focused on sustaining the results of Phase 1.
      Intervention Phase 2 focused on total prevention of hyperthermia by initiating
      cooling blanket use immediately upon patient arrival to the intensive care unit.
      RESULTS The median hyperthermia duration in the preintervention cohort (n = 47)
      was 135 minutes. This was reduced in the Phase 1 cohort (n = 9) to 45 minutes,
      increased in the maintenance phase cohort (n = 6) to 88.5 minutes, and decreased
      again in the Phase 2 cohort (n = 9) to a median value of 0 minutes. Eight percent
      of patients in the intervention cohorts required additional sedation to tolerate
      the cooling blanket. Eight percent of patients in the intervention cohorts became
      briefly hypothermic while on the cooling blanket. No patient required
      neuromuscular blockade to tolerate the cooling blanket, experienced an
      arrhythmia, had new coagulopathy, or developed a pressure ulcer. CONCLUSIONS The
      placement of a cooling blanket on the bed prior to patient arrival and actively
      targeting normothermia successfully reduced the incidence and duration of
      hyperthermia with minimal adverse events.

PMID- 29192868
TI  - Bullough's bump: unusual protuberant fibro-osseous tumor of the temporal bone.
      Case report.
AB  - Scalp and calvarial masses are common in children and the differential diagnosis
      is broad. The authors recently cared for a child with an unusual fibro-osseous
      lesion of the temporal bone that has previously not been described in the
      pediatric neurosurgery literature. A 10-year-old girl presented with a firm,
      slowly enlarging protuberant mass arising from the squamous suture of the
      temporal bone without intracranial extension. The mass was removed en bloc
      through a temporal craniectomy and cranioplasty was performed. The patient had a
      smooth postoperative course. Histological examination showed multiple oval
      osseous islands dispersed throughout a bland fibrous stroma. The pathological
      diagnosis was "Bullough's bump," a rare, benign fibro-osseous neoplasm first
      described in 1999, and only 8 reported cases appear in the literature. Here the
      authors report the first case of Bullough's bump in a child.

PMID- 29192869
TI  - Predictors of clinical outcome in pediatric oligodendroglioma: meta-analysis of
      individual patient data and multiple imputation.
AB  - OBJECTIVE Oligodendroglioma is a rare primary CNS neoplasm in the pediatric
      population, and only a limited number of studies in the literature have
      characterized this entity. Existing studies are limited by small sample sizes and
      discrepant interstudy findings in identified prognostic factors. In the present
      study, the authors aimed to increase the statistical power in evaluating for
      potential prognostic factors of pediatric oligodendrogliomas and sought to
      reconcile the discrepant findings present among existing studies by performing an
      individual-patient-data (IPD) meta-analysis and using multiple imputation to
      address data not directly available from existing studies. METHODS A systematic
      search was performed, and all studies found to be related to pediatric
      oligodendrogliomas and associated outcomes were screened for inclusion. Each
      study was searched for specific demographic and clinical characteristics of each
      patient and the duration of event-free survival (EFS) and overall survival (OS).
      Given that certain demographic and clinical information of each patient was not
      available within all studies, a multivariable imputation via chained equations
      model was used to impute missing data after the mechanism of missing data was
      determined. The primary end points of interest were hazard ratios for EFS and OS,
      as calculated by the Cox proportional-hazards model. Both univariate and
      multivariate analyses were performed. The multivariate model was adjusted for
      age, sex, tumor grade, mixed pathologies, extent of resection, chemotherapy,
      radiation therapy, tumor location, and initial presentation. A p value of less
      than 0.05 was considered statistically significant. RESULTS A systematic search
      identified 24 studies with both time-to-event and IPD characteristics available,
      and a total of 237 individual cases were available for analysis. A median of
      19.4% of the values among clinical, demographic, and outcome variables in the
      compiled 237 cases were missing. Multivariate Cox regression analysis revealed
      subtotal resection (p = 0.007 [EFS] and 0.043 [OS]), initial presentation of
      headache (p = 0.006 [EFS] and 0.004 [OS]), mixed pathologies (p = 0.005 [EFS] and
      0.049 [OS]), and location of the tumor in the parietal lobe (p = 0.044 [EFS] and
      0.030 [OS]) to be significant predictors of tumor progression or recurrence and
      death. CONCLUSIONS The use of IPD meta-analysis provides a valuable means for
      increasing statistical power in investigations of disease entities with a very
      low incidence. Missing data are common in research, and multiple imputation is a
      flexible and valid approach for addressing this issue, when it is used
      conscientiously. Undergoing subtotal resection, having a parietal tumor, having
      tumors with mixed pathologies, and suffering headaches at the time of diagnosis
      portended a poorer prognosis in pediatric patients with oligodendroglioma.

PMID- 29192870
TI  - Spatial Analysis of Handwritten Texts as a Marker of Cognitive Control.
AB  - We explore the idea that cognitive demands of the handwriting would influence the
      degree of automaticity of the handwriting process, which in turn would affect the
      geometric parameters of texts. We compared the heterogeneity of handwritten texts
      in tasks with different cognitive demands; the heterogeneity of texts was
      analyzed with lacunarity, a measure of geometrical invariance. In Experiment 1,
      we asked participants to perform two tasks that varied in cognitive demands:
      transcription and exposition about an autobiographical episode. Lacunarity was
      significantly lower in transcription. In Experiment 2, we compared a veridical
      and a fictitious version of a personal event. Lacunarity was lower in veridical
      texts. We contend that differences in lacunarity of handwritten texts reveal the
      degree of automaticity in handwriting.

PMID- 29192871
TI  - What Does the DAP:IQ Measure?: Drawing Comparisons between Drawing Performance
      and Developmental Assessments.
AB  - Human figure drawing tasks such as the Draw-a-Person test have long been used to
      assess intelligence (F. Goodenough, 1926). The authors investigate the skills
      tapped by drawing and the risk factors associated with poor drawing. Self
      portraits of 345 preschool children were scored by raters trained in using the
      Draw-a-Person Intellectual Ability test (DAP:IQ) rubric (C. R. Reynolds & J. A.
      Hickman, 2004). Analyses of children's fine motor, gross motor, social,
      cognitive, and language skills revealed that only fine motor skill was an
      independent predictor of DAP:IQ scores. Being a boy and having a low birth weight
      were associated with lower DAP:IQ scores. These findings suggest that although
      the DAP:IQ may not be a valid measure of cognitive ability, it may be a useful
      screening tool for fine motor disturbances in at-risk children, such as boys who
      were born at low birth weights. Furthermore, researchers who use human figure
      drawing tasks to measure intelligence should measure fine motor skill in addition
      to intelligence.

PMID- 29192872
TI  - Experience of Being Young With Psoriasis: Self-Management Support Needs.
AB  - Psoriasis is a long-term condition with a possibly cumulative life course
      impairment. Young people struggle to minimize its effects on appearance and
      functioning. To date, the self-management needs of adolescents suffering from
      psoriasis have been underinvestigated. Using focus groups and individual
      interviews, we present an interpretive description of young people's experiences
      of living with psoriasis, the challenges they face, and the support they need to
      relieve suffering and come to terms with their condition. This process is
      characterized by loneliness, the self-imposition of limitations, and the lack of
      personalized knowledge and communication skills to manage the impact of disease
      and society's reactions. Our study provides insight into needs of early
      interventions tailored to address condition, role, and emotional management,
      involving parent education, peer support, storytelling, and roles for
      professionals. We argue that further research should involve young people, their
      parents, and professionals in the development and evaluation of interventions.

PMID- 29192873
TI  - Incidence of first stroke and ethnic differences in stroke pattern in Bradford,
      UK: Bradford Stroke Study.
AB  - Background Information on ethnic disparities in stroke between White and
      Pakistani population in Europe is scarce. Bradford District has the largest
      proportion of Pakistani people in England; this provides a unique opportunity to
      study the difference in stroke between the two major ethnic groups. Aim To
      determine the first-ever-stroke incidence and examine the disparities in stroke
      patterns between Whites and Pakistanis in Bradford. Methods Prospective 12 months
      study consisting of 273,327 adults (>=18 years) residents. Stroke cases were
      identified by multiple overlapping approaches. Results In the study period, 541
      first-ever-strokes were recorded. The crude incidence rate was 198 per 100,000
      person-years. Age adjusted-standardized rate to the World Health Organization
      world population of first-ever-stroke is 155 and 101 per 100,000 person-years in
      Pakistanis and Whites respectively. Four hundred and thirty-eight patients (81%)
      were Whites, 83 (15.3%) were Pakistanis, 11 (2%) were Indian and Bangladeshis,
      and 9 (1.7%) were of other ethnic origin. Pakistanis were significantly younger
      and had more obesity ( p = 0.049), and diabetes mellitus (DM) ( p = <0.001). They
      were less likely to suffer from atrial fibrillation ( p = <0.001), be ex- or
      current smokers ( p = <0.001), and drink alcohol above the recommended level ( p
      = 0.007) compared with Whites. In comparison with Whites, higher rates of age
      adjusted stroke (1.5-fold), lacunar infarction (threefold), and ischemic
      infarction due to large artery disease (twofold) were found in the Pakistanis.
      Conclusions The incidence of first-ever-stroke is higher in the Pakistanis
      compared with the Whites in Bradford, UK. Etiology and vascular risk factors vary
      between the ethnic groups. This information should be considered when
      investigating stroke etiology, and when planning prevention and care provision to
      improve outcomes after stroke.

PMID- 29192874
TI  - Young Children's ability to Discriminate between Antisocial and Prosocial Teases.
AB  - The present study was designed to (a) examine 5- to 8-year-old children's ability
      to discriminate between antisocial and prosocial teases and (b) determine whether
      their age and experiences within the home are associated with their ability to
      recognize these two types of teases. Results revealed that the 5- to 8-year-old
      children were able to discriminate between antisocial and prosocial teases.
      Although the children's parents or legal guardians indicated that the children
      had more frequent experience with prosocial than antisocial teases in the home,
      (a) the children were better able to correctly identify the intent of antisocial
      teasers than prosocial teasers and (b) the parents or legal guardians (correctly)
      indicated that their child would be better able to recognize an antisocial tease
      than a prosocial tease. Despite the finding that the children's comprehension of
      antisocial teasing tended to exceed their comprehension of prosocial teasing, the
      findings indicate that being relatively young (i.e., 5-6 years old vs. 7-8 years
      old) and having relatively frequent experience with antisocial teasing in the
      home may be associated with some children's difficulty in recognizing the intent
      behind antisocial teases.

PMID- 29192875
TI  - Circumferential dural resection technique and reconstruction for the removal of
      giant calcified transdural herniated thoracic discs.
AB  - OBJECTIVE The authors report a novel paradigm for resection of the disc or dural
      complex to treat giant calcified transdural herniated thoracic discs, and they
      describe a technique for the repair of dural defects. These herniated thoracic
      discs are uncommon, complicated lesions that often require a multidisciplinary
      team for effective treatment. The intradural component must be removed to
      effectively decompress the spinal cord. The opening of the friable dura mater,
      which frequently adheres to the extradural component of the disc, can result in
      large defects and difficult-to-manage CSF leaks. METHODS The authors performed a
      retrospective study of the technique and outcomes in patients with a transdural
      herniated disc treated at St. Joseph's Hospital and Medical Center within a 4
      year period between 2012 and 2015. RESULTS During the study period, 7 patients
      (mean age 56.1 years) presented to the department of neurosurgery with clinical
      symptoms consistent with myeloradiculopathy. In all cases, 2-level corpectomies
      of the involved levels were combined with circumferential resection of the dura
      and complete decompression of the spinal cord. The dural defect was repaired with
      an onlay dural patch, and a large piece of AlloDerm (LifeCell Corp) graft was
      sewn to close the pleural defect. Every patient had a perioperative lumbar drain
      placed for CSF diversion. No patient suffered neurological decline related to the
      surgery, and 3 patients experienced clinically significant improvement in
      function. Two patients developed an early postoperative CSF leak that required
      operative revision to oversew the defects. CONCLUSIONS This novel technique for
      decompression of the spinal cord by dural resection for the removal of giant
      calcified transdural herniated thoracic discs is safe and results in excellent
      decompression of the spinal cord. The technique becomes necessary when primary
      repair of the dura is not possible, and it can be used in cases in which the
      resection of pathology includes the dura.

PMID- 29192876
TI  - Posterior inferior cerebellar artery with an extradural origin from the V3
      segment: higher incidence on the nondominant vertebral artery.
AB  - OBJECTIVE The posterior inferior cerebellar artery (PICA) and the vertebral
      artery (VA) often exhibit anatomical variations at the craniovertebral junction
      (CVJ). An example of this is the PICA originating extradurally from the V3
      segment of the VA. To date, some cadaveric investigations have been reported, but
      the incidence and relationship of this variation to the VA and the atlas as
      observed on clinical imaging have not been discussed. This study evaluated the
      prevalence of PICAs originating from the V3 on CT scanning. Other variations of
      the atlas and VA were also analyzed. METHODS CT images from a series of 153
      patients who underwent 3D CT angiography (CTA) were analyzed, and variations of
      the PICA, VA, and atlas were investigated. RESULTS A total of 142 patients (284
      sides) were analyzed; 11 patients (7.2%) were excluded due to poor image quality.
      The most common VA variation was the PICA originating from V3 (9.5% of 284
      sides), which was more frequently observed on the nondominant VA than the
      dominant VA (22.5% vs 6.25%, p = 0.0005). A VA with a PICA end was identified in
      4 sides (1.4%), which is the same incidence as observed in the persistent first
      intersegmental VA (1.4%). VA fenestration was only found in 1 side (0.35%).
      Regarding the atlas, ponticulus posticus was observed in 24 sides (8.5%). There
      was no relationship between the incidence of ponticulus posticus and the
      variations of the VA. CONCLUSIONS A PICA originating from V3 was the most common
      VA variation at the CVJ and was more common on the nondominant VA. Three
      dimensional CTA is useful for the evaluation of this variance. Surgeons should be
      mindful of this variation during operations.

PMID- 29192877
TI  - Impact of body mass index on surgical outcomes, narcotics consumption, and
      hospital costs following anterior cervical discectomy and fusion.
AB  - OBJECTIVE Given the increasing prevalence of obesity, more patients with a high
      body mass index (BMI) will require surgical treatment for degenerative spinal
      disease. In previous investigations of lumbar spine pathology, obesity has been
      associated with worsened postoperative outcomes and increased costs. However, few
      studies have examined the association between BMI and postoperative outcomes
      following anterior cervical discectomy and fusion (ACDF) procedures. Thus, the
      purpose of this study was to compare surgical outcomes, postoperative narcotics
      consumption, complications, and hospital costs among BMI stratifications for
      patients who have undergone primary 1- to 2-level ACDF procedures. METHODS The
      authors retrospectively reviewed a prospectively maintained surgical database of
      patients who had undergone primary 1- to 2-level ACDF for degenerative spinal
      pathology between 2008 and 2015. Patients were stratified by BMI as follows:
      normal weight (< 25.0 kg/m2), overweight (25.0-29.9 kg/m2), obese I (30.0-34.9
      kg/m2), or obese II-III (>= 35.0 kg/m2). Differences in patient demographics and
      preoperative characteristics were compared across the BMI cohorts using 1-way
      ANOVA or chi-square analysis. Multivariate linear or Poisson regression with
      robust error variance was used to determine the presence of an association
      between BMI category and narcotics utilization, improvement in visual analog
      scale (VAS) scores, incidence of complications, arthrodesis rates, reoperation
      rates, and hospital costs. Regression analyses were controlled for preoperative
      demographic and procedural characteristics. RESULTS Two hundred seventy-seven
      patients were included in the analysis, of whom 20.9% (n = 58) were normal
      weight, 37.5% (n = 104) were overweight, 24.9% (n = 69) were obese I, and 16.6%
      (n = 46) were obese II-III. A higher BMI was associated with an older age (p =
      0.049) and increased comorbidity burden (p = 0.001). No differences in sex,
      smoking status, insurance type, diagnosis, presence of neuropathy, or
      preoperative VAS pain scores were found among the BMI cohorts (p > 0.05). No
      significant differences were found among these cohorts as regards operative time,
      intraoperative blood loss, length of hospital stay, and number of operative
      levels (p > 0.05). Additionally, no significant differences in postoperative
      narcotics consumption, VAS score improvement, complication rates, arthrodesis
      rates, reoperation rates, or total direct costs existed across BMI
      stratifications (p > 0.05). CONCLUSIONS Patients with a higher BMI demonstrated
      surgical outcomes, narcotics consumption, and hospital costs comparable to those
      of patients with a lower BMI. Thus, ACDF procedures are both safe and effective
      for all patients across the entire BMI spectrum. Patients should be counseled to
      expect similar rates of postoperative complications and eventual clinical
      improvement regardless of their BMI.

PMID- 29192878
TI  - Motion-preserving, 2-stage transoral and posterior treatment of an unstable
      Jefferson fracture in a professional football player.
AB  - The authors report the case of a patient who suffered a Jefferson fracture during
      a professional football game. The C-1 (atlas) fracture was widely displaced
      anteriorly, but the transverse ligament was intact. In an effort to enable a
      return to play and avoid intersegmental (C1-2) fusion, the patient underwent a
      transoral approach for open reduction and internal fixation of the fracture. The
      associated posterior ring fracture displacement widened after this procedure, and
      a subsequent posterior arthrodesis and fixation of the fracture site was
      performed 6 months later when the fracture failed to heal with rigid collar
      immobilization. The approach maintained the normal range of motion at the
      atlantoaxial and atlantooccipital joints, which would have been sacrificed by an
      atlantoaxial or occipitocervical fusion, as is traditionally performed.
      Ultimately, the patient decided not to return to the football field, but this
      approach could avoid the more significant loss of motion associated with
      atlantoaxial or occipitocervical fusion for unstable Jefferson fractures.

PMID- 29192879
TI  - Pedicle screw placement accuracy using ultra-low radiation imaging with image
      enhancement versus conventional fluoroscopy in minimally invasive transforaminal
      lumbar interbody fusion: an internally randomized controlled trial.
AB  - OBJECTIVE A previous study found that ultra-low radiation imaging (ULRI) with
      image enhancement significantly decreases radiation exposure by roughly 75% for
      both the patient and operating room personnel during minimally invasive
      transforaminal lumbar interbody fusion (MIS-TLIF) (p < 0.001). However, no
      clinical data exist on whether this imaging modality negatively impacts patient
      outcomes. Thus, the goal of this randomized controlled trial was to assess
      pedicle screw placement accuracy with ULRI with image enhancement compared with
      conventional, standard-dose fluoroscopy for patients undergoing single-level MIS
      TLIF. METHODS An institutional review board-approved, prospective internally
      randomized controlled trial was performed to compare breach rates for pedicle
      screw placement performed using ULRI with image enhancement versus conventional
      fluoroscopy. For cannulation and pedicle screw placement, surgery on 1 side (left
      vs right) was randomly assigned to be performed under ULRI. Screws on the
      opposite side were placed under conventional fluoroscopy, thereby allowing each
      patient to serve as his/her own control. In addition to standard intraoperative
      images to check screw placement, each patient underwent postoperative CT. Three
      experienced neurosurgeons independently analyzed the images and were blinded as
      to which imaging modality was used to assist with each screw placement. Screw
      placement was analyzed for pedicle breach (lateral vs medial and Grade 0 [< 2.0
      mm], Grade 1 [2.0-4.0 mm], or Grade 2 [> 4.0 mm]), appropriate screw depth (50%
      75% of the vertebral body's anteroposterior dimension), and appropriate screw
      angle (within 10 degrees  of the pedicle angle). The effective breach rate was
      calculated as the percentage of screws evaluated as breached > 2.0 mm medially or
      postoperatively symptomatic. RESULTS Twenty-three consecutive patients underwent
      single-level MIS-TLIF, and their sides were randomly assigned to receive ULRI. No
      patient had immediate postoperative complications (e.g., neurological decline,
      need for hardware repositioning). On CT confirmation, 4 screws that had K-wire
      placement and cannulation under ULRI and screw placement under conventional
      fluoroscopy showed deviations. There were 2 breaches that deviated medially but
      both were Grade 0 (< 2.0 mm). Similarly, 2 breaches occurred that were Grade 1 (>
      2.0 mm) but both deviated laterally. Therefore, the effective breach rate (breach
      > 2.0 mm deviated medially) was unchanged in both imaging groups (0% using either
      ULRI or conventional fluoroscopy; p = 1.00). CONCLUSIONS ULRI with image
      enhancement does not compromise accuracy during pedicle screw placement compared
      with conventional fluoroscopy while it significantly decreases radiation exposure
      to both the patient and operating room personnel.

PMID- 29192881
TI  - EOV "Editorial Board".

PMID- 29192880
TI  - Negative-pressure dressing management of recurrent postoperative epidural
      hematoma and uncontrollable intraoperative hemorrhage in posterior spine surgery:
      report of 4 cases.
AB  - There is a paucity of literature describing the management of recurrent
      symptomatic postoperative epidural hematoma or uncontrollable intraoperative
      hemorrhage in posterior spine surgery. Traditional management with hematoma
      evacuation and wound closure over suction drains may not be effective in certain
      cases, and it can lead to recurrence and neurological injury. The authors report
      3 cases of recurrent symptomatic postoperative epidural hematoma successfully
      managed with novel open-wound negative-pressure dressing therapy (NPDT), as well
      as 1 case of uncontrollable intraoperative hemorrhage that was primarily managed
      with the same technique. The 3 patients who developed a postoperative epidural
      hematoma became symptomatic 2-17 days after the initial operation. All 3 patients
      underwent at least 1 hematoma evacuation and wound closure over suction drains
      prior to recurrence with severe neurological deficit and definitive management
      with NPDT. One patient was managed primarily with NPDT for uncontrollable
      intraoperative hemorrhage during posterior cervical laminectomy. All 4 patients
      had significant risk factors for postoperative epidural hematoma. NPDT for 3-9
      days with delayed wound closure was successful in all patients. The 3 patients
      with recurrent symptomatic postoperative epidural hematoma had significant
      improvement in their severe neurological deficit. None of the patients developed
      a postoperative wound infection, and none of the patients required transfusion
      due to NPDT. NPDT with delayed wound closure may be an option in certain
      patients, when wound closure over suction drains is unlikely to prevent further
      neurological injury.

PMID- 29192883
TI  - EMS Coverage of a Female-Only Event with 10,000 Attendees: Preparation and
      Implementation in One Week.
AB  - This report describes the medical coverage provided for 10KSA, a charity event
      held in Saudi Arabia for breast cancer awareness. More than 10,000 women attended
      the event. A total of 41 attendees sought medical care; four patients (9.8%)
      presented directly to the clinic and 37 patients (90.2%) presented to the first
      aid units, mostly for check-ups. This report may be helpful for care providers
      arranging medical coverage for future events with similar challenging situations
      (women only, distant location). AlAssaf WI . EMS coverage of a female-only event
      with 10,000 attendees: preparation and implementation in one week. Prehosp
      Disaster Med. 2017;32(6):694-698.

PMID- 29192884
TI  - 911 Patient Redirection.
AB  - Sporer KA . 911 patient redirection. Prehosp Disaster Med. 2017;32(6):589-592.

PMID- 29192886
TI  - Limited-Range Few-View CT: Using Historical Images for ROI Reconstruction in
      Solitary Lung Nodules Follow-up Examination.
AB  - Repeated CT scans are known to increase the risk of cancer; thus, it is
      paradoxical to use multiple follow-up CT scans to monitor the development of a
      lung nodule and conduct early treatment of the nodule. In the case of a solitary
      lung nodule, regional scanning and region of interest (ROI) reconstruction are
      likely to restore the internal area at the nodule. A limited-range few-view CT is
      proposed in this paper for lung nodule follow-ups with extremely reduced X
      radiation. For a planned scanning of an ROI, where a solitary lung nodule is
      positioned, a limited-range few-view CT can be employed, and thus, less tissue is
      exposed to X-radiation per view. An ROI reconstruction method is also proposed
      that makes full use of the former standard lung scan. The experimental results
      show that the nodule size and shape are preserved. In the case of a 40-mm ROI,
      the number of exposed X-rays can be reduced by 99.6% for a circular scan and
      99.9% for a 3-D scan.

PMID- 29192885
TI  - Robust Low-Dose CT Sinogram Preprocessing via Exploiting Noise-Generating
      Mechanism.
AB  - Computed tomography (CT) image recovery from low-mAs acquisitions without
      adequate treatment is always severely degraded due to a number of physical
      factors. In this paper, we formulate the low-dose CT sinogram preprocessing as a
      standard maximum a posteriori (MAP) estimation, which takes full consideration of
      the statistical properties of the two intrinsic noise sources in low-dose CT,
      i.e., the X-ray photon statistics and the electronic noise background. In
      addition, instead of using a general image prior as found in the traditional
      sinogram recovery models, we design a new prior formulation to more rationally
      encode the piecewise-linear configurations underlying a sinogram than previously
      used ones, like the TV prior term. As compared with the previous methods,
      especially the MAP-based ones, both the likelihood/loss and prior/regularization
      terms in the proposed model are ameliorated in a more accurate manner and better
      comply with the statistical essence of the generation mechanism of a practical
      sinogram. We further construct an efficient alternating direction method of
      multipliers algorithm to solve the proposed MAP framework. Experiments on
      simulated and real low-dose CT data demonstrate the superiority of the proposed
      method according to both visual inspection and comprehensive quantitative
      performance evaluation.

PMID- 29192887
TI  - A Feasibility Study of Low-Dose Single-Scan Dual-Energy Cone-Beam CT in Many-View
      Under-Sampling Framework.
AB  - A single-scan dual-energy low-dose cone-beam CT (CBCT) imaging technique that
      exploits a multi-slit filter is proposed in this paper. The multi-slit filter
      installed between the x-ray source and the scanned object is reciprocated during
      a scan. The x-ray beams through the slits would generate relatively low-energy x
      ray projection data, while the filtered beams would make high-energy projection
      data. An iterative image reconstruction algorithm that uses an adaptive-steepest
      descent method to minimize image total-variation under the constraint of data
      fidelity was applied to reconstructing the image from the low-energy projection
      data. Since the high-energy projection data suffer from a substantially high
      noise level due to the beam filtration, we have developed a new algorithm that
      exploits the joint sparsity between the low- and high-energy CT images for image
      reconstruction of the high-energy CT image. The proposed image reconstruction
      algorithm uses a gradient magnitude image (GMI) of the low-energy CT image by
      regularizing the difference of GMIs of the low- and high-energy CT images to be
      minimized. The feasibility of the proposed technique has been demonstrated by the
      use of various phantoms in the experimental CBCT setup. Furthermore, based on the
      proposed dual-energy imaging, a material differentiation was performed and its
      potential utility has been shown. The proposed imaging technique produced
      promising results for its potential application to a low-dose single-scan dual
      energy CBCT.

PMID- 29192889
TI  - Hydration water dynamics around a protein surface: a first passage time approach.
AB  - A stochastic noise-driven dynamic model is proposed to study the diffusion of
      water molecules around a protein surface, under the effect of thermal
      fluctuations that arise due to the collision of water molecules with the
      surrounding environment. The underlying dynamics of such a system may be
      described in the framework of the generalized Langevin equation, where the
      thermal fluctuations are assumed to be algebraically correlated in time, which
      governs the non-Markovian behavior of the system. Results of the calculations of
      mean-square displacement and the velocity autocorrelation function reveal that
      the hydration water around the protein surface follows subdiffusive dynamics at
      long times. Analytical expressions for the first passage time distribution,
      survival probability, mean residence time and mean first passage time of water
      molecules are derived for different boundary conditions, to analyze hydration
      water dynamics under the effect of thermally correlated noise. The results depict
      a unimodal distribution of the first passage time unlike Brownian motion. The
      survival probability of hydration water follows a stretched exponential decay for
      both boundary conditions. The mean residence time of the hydration water molecule
      for different initial positions increases with increase in the
      complexity/heterogeneity of the surrounding environment for both boundary
      conditions. The mean first passage time of the water molecule to reach the
      absorbing/reflecting boundary follows an asymptotic power law with respect to the
      thickness of the hydration layer, and increases with increase in the
      complexity/heterogeneity of the environment.

PMID- 29192888
TI  - Low-Dose CBCT Reconstruction Using Hessian Schatten Penalties.
AB  - Cone-beam computed tomography (CBCT) has been widely used in radiation therapy.
      For accurate patient setup and treatment target localization, it is important to
      obtain high-quality reconstruction images. The total variation (TV) penalty has
      shown the state-of-the-art performance in suppressing noise and preserving edges
      for statistical iterative image reconstruction, but it sometimes leads to the so
      called staircase effect. In this paper, we proposed to use a new family of
      penalties-the Hessian Schatten (HS) penalties-for the CBCT reconstruction.
      Consisting of the second-order derivatives, the HS penalties are able to reflect
      the smooth intensity transitions of the underlying image without introducing the
      staircase effect. We discussed and compared the behaviors of several convex HS
      penalties with orders 1, 2, and for CBCT reconstruction. We used the majorization
      minimization approach with a primal-dual formulation for the corresponding
      optimization problem. Experiments on two digital phantoms and two physical
      phantoms demonstrated the proposed penalty family's outstanding performance over
      TV in suppressing the staircase effect, and the HS penalty with order 1 had the
      best performance among the HS penalties tested.

PMID- 29192890
TI  - Van der Waals heterojunction diode composed of WS2 flake placed on p-type Si
      substrate.
AB  - P-N junctions represent the fundamental building blocks of most semiconductors
      for optoelectronic functions. This work demonstrates a technique for forming a
      WS2/Si van der Waals junction based on mechanical exfoliation. Multilayered WS2
      nanoflakes were exfoliated on the surface of bulk p-type Si substrates using a
      polydimethylsiloxane stamp. We found that the fabricated WS2/Si p-n junctions
      exhibited rectifying characteristics. We studied the effect of annealing
      processes on the performance of the WS2/Si van der Waals p-n junction and
      demonstrated that annealing improved its electrical characteristics. However,
      devices with vacuum annealing have an enhanced forward-bias current compared to
      those annealed in a gaseous environment. We also studied the top-gate-tunable
      rectification characteristics across the p-n junction interface in experiments as
      well as density functional theory calculations. Under various temperatures, Zener
      breakdown occurred at low reverse-bias voltages, and its breakdown voltage
      exhibited a negative coefficient of temperature. Another breakdown voltage was
      observed, which increased with temperature, suggesting a positive coefficient of
      temperature. Therefore, such a breakdown can be assigned to avalanche breakdown.
      This work demonstrates a promising application of two-dimensional materials
      placed directly on conventional bulk Si substrates.

PMID- 29192891
TI  - Comparison of different functional EIT approaches to quantify tidal ventilation
      distribution.
AB  - OBJECTIVE: The aim of the study was to examine the pros and cons of different
      types of functional EIT (fEIT) to quantify tidal ventilation distribution in a
      clinical setting. APPROACH: fEIT images were calculated with (1) standard
      deviation of pixel time curve, (2) regression coefficients of global and local
      impedance time curves, or (3) mean tidal variations. To characterize temporal
      heterogeneity of tidal ventilation distribution, another fEIT image of pixel
      inspiration times is also proposed. MAIN RESULTS: fEIT-regression is very robust
      to signals with different phase information. When the respiratory signal should
      be distinguished from the heart-beat related signal, or during high-frequency
      oscillatory ventilation, fEIT-regression is superior to other types. fEIT-tidal
      variation is the most stable image type regarding the baseline shift. We
      recommend using this type of fEIT image for preliminary evaluation of the
      acquired EIT data. However, all these fEITs would be misleading in their
      assessment of ventilation distribution in the presence of temporal heterogeneity.
      SIGNIFICANCE: The analysis software provided by the currently available
      commercial EIT equipment only offers either fEIT of standard deviation or tidal
      variation. Considering the pros and cons of each fEIT type, we recommend
      embedding more types into the analysis software to allow the physicians dealing
      with more complex clinical applications with on-line EIT measurements.

PMID- 29192892
TI  - Electronic and thermoelectric properties of atomically thin
      C<sub>3</sub>Si<sub>3</sub>/C and C<sub>3</sub>Ge<sub>3</sub>/C superlattices.
AB  - The nanostructuring of graphene into superlattices offers the possibility of
      tuning both the electronic and thermal properties of graphene. Using classical
      and quantum mechanical calculations, we have investigated the electronic and
      thermoelectric properties of the atomically thin superlattice of C3Si3/C
      (C3Ge3/C) formed by the incorporation of Si (Ge) atoms into graphene. The bandgap
      and phonon thermal conductivity of C3Si3/C (C3Ge3/C) are 0.54 (0.51) eV and 15.48
      (12.64) Wm-1K-1, respectively, while the carrier mobility of C3Si3/C (C3Ge3/C) is
      1.285 x 105 (1.311 x 105) cm2V-1s-1 at 300 K. The thermoelectric figure of merit
      for C3Si3/C (C3Ge3/C) can be optimized via the tuning of carrier concentration to
      obtain the prominent ZT value of 1.95 (2.72).

PMID- 29192893
TI  - Electric field tuned MoS<sub>2</sub>/metal interface for hydrogen evolution
      catalyst from first-principles investigations.
AB  - Understanding the interfacial properties of catalyst/substrate is crucial for the
      design of high-performance catalyst for important chemical reactions. Recent
      years have witnessed a surge of research in utilizing MoS2 as a promising electro
      catalyst for hydrogen production, and field effect has been employed to enhance
      the activity (Adv. Mater. 2017, 29, 1604464; Nano Lett. 2017, 17, 4109). However,
      the underlying atomic mechanism remains unclear. In this paper, by using the
      prototype MoS2/Au system as a probe, we investigate effects of external electric
      field on the interfacial electronic structures via density functional theory
      (DFT) based first-principles calculations. Our results reveal that although there
      is no covalent interaction between MoS2 overlayer and Au substrate, an applied
      electric field efficiently adjusts the charge transfer between MoS2 and Au,
      leading to tunable Schottky barrier type (n-type to p-type) and decrease of
      barrier height to facilitate charge injection. Furthermore, we predict that the
      adsorption energy of atomic hydrogen on MoS2/Au to be readily controlled by
      electric field to a broad range within a modest magnitude of field, which may
      benefit the performance enhancement of hydrogen evolution reaction. Our DFT
      results provide valuable insight into the experimental observations and pave the
      way for future understanding and control of catalysts in practice, such as those
      with vacancies, defects, edge states or synthesized nanostructures.

PMID- 29192894
TI  - Photoelectrochemical studies of InGaN/GaN MQW photoanodes.
AB  - The research interest in photoelectrochemical (PEC) water splitting is ever
      growing due to its potential to contribute towards clean and portable energy.
      However, the lack of low energy band gap materials with high photocorrosion
      resistance is the primary setback inhibiting this technology from
      commercialisation. The ternary alloy InGaN shows promise to meet the
      photoelectrode material requirements due to its high chemical stability and band
      gap tunability. The band gap of InGaN can be modulated from the UV to IR regions
      by adjusting the In concentration so as to absorb the maximum portion of the
      solar spectrum. This paper reports on the influence of In concentration on the
      PEC properties of planar and nanopillar (NP) InGaN/GaN multi-quantum well (MQW)
      photoanodes, where NPs were fabricated using a top-down approach. Results show
      that changing the In concentration, while having a minor effect on the PEC
      performance of planar MQWs, has an enormous impact on the PEC performance of NP
      MQWs, with large variations in the photocurrent density observed. Planar
      photoanodes containing MQWs generate marginally lower photocurrents compared to
      photoanodes without MQWs when illuminated with sunlight. NP MQWs with 30% In
      generated the highest photocurrent density of 1.6 mA cm-2, 4 times greater than
      that of its planar counterpart and 1.8 times greater than that of the NP
      photoanode with no MQWs. The InGaN/GaN MQWs also slightly influenced the onset
      potential of both the planar and NP photoanodes. Micro-photoluminescence, diffuse
      reflectance spectroscopy and IPCE measurements are used to explain these results.

PMID- 29192896
TI  - Superior early periprocedural efficacy of prasugrel over ticagrelor in patients
      after stenting.

PMID- 29192895
TI  - How asymptomatic is "asymptomatic" carotid stenosis? Resolving fundamental
      confusion(s) - and confusions yet to be resolved.

PMID- 29192897
TI  - Association between the presence of autoantibodies against adrenoreceptors and
      hypertensive disorders in pregnancy: a pilot study.

PMID- 29192898
TI  - Comment on "Behcet disease: a rare systemic vasculitis in Poland".

PMID- 29192899
TI  - Comment on "Behcet disease: a rare systemic vasculitis in Poland": authors'
      reply.

PMID- 29192901
TI  - Corrections.

PMID- 29192900
TI  - Towards a better education of patients with atrial fibrillation: the initiative
      of the Polish Cardiac Society.

PMID- 29192903
TI  - Rare symbionts may contribute to the resilience of coral-algal assemblages.
AB  - The association between corals and photosynthetic dinoflagellates (Symbiodinium
      spp.) is the key to the success of reef ecosystems in highly oligotrophic
      environments, but it is also their Achilles' heel due to its vulnerability to
      local stressors and the effects of climate change. Research during the last two
      decades has shaped a view that coral host-Symbiodinium pairings are diverse, but
      largely exclusive. Deep sequencing has now revealed the existence of a rare
      diversity of cryptic Symbiodinium assemblages within the coral holobiont, in
      addition to one or a few abundant algal members. While the contribution of the
      most abundant resident Symbiodinium species to coral physiology is widely
      recognized, the significance of the rare and low abundant background Symbiodinium
      remains a matter of debate. In this study, we assessed how coral-Symbiodinium
      communities assemble and how rare and abundant components together constitute the
      Symbiodinium community by analyzing 892 coral samples comprising >110 000 unique
      Symbiodinium ITS2 marker gene sequences. Using network modeling, we show that
      host-Symbiodinium communities assemble in non-random 'clusters' of abundant and
      rare symbionts. Symbiodinium community structure follows the same principles as
      bacterial communities, for which the functional significance of rare members (the
      'rare bacterial biosphere') has long been recognized. Importantly, the inclusion
      of rare Symbiodinium taxa in robustness analyses revealed a significant
      contribution to the stability of the host-symbiont community overall. As such, it
      highlights the potential functions rare symbionts may provide to environmental
      resilience of the coral holobiont.

PMID- 29192902
TI  - Relevance of the p53-MDM2 axis to aging.
AB  - In response to varying stress signals, the p53 tumor suppressor is able to
      promote repair, survival, or elimination of damaged cells - processes that have
      great relevance to organismal aging. Although the link between p53 and cancer is
      well established, the contribution of p53 to the aging process is less clear.
      Delineating how p53 regulates distinct aging hallmarks such as cellular
      senescence, genomic instability, mitochondrial dysfunction, and altered metabolic
      pathways will be critical. Mouse models have further revealed the centrality and
      complexity of the p53 network in aging processes. While naturally aged mice have
      linked longevity with declining p53 function, some accelerated aging mice present
      with chronic p53 activation, whose phenotypes can be rescued upon p53 deficiency.
      Further, direct modulation of the p53-MDM2 axis has correlated elevated p53
      activity with either early aging or with delayed-onset aging. We speculate that
      p53-mediated aging phenotypes in these mice must have (1) stably active p53 due
      to MDM2 dysregulation or chronic stress or (2) shifted p53 outcomes. Pinpointing
      which p53 stressors, modifications, and outcomes drive aging processes will
      provide further insights into our understanding of the human aging process and
      could have implications for both cancer and aging therapeutics.

PMID- 29192906
TI  - Infrared spectroscopy of hydrated polycyclic aromatic hydrocarbon cations:
      naphthalene+-water.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are suggested to occur in interstellar
      media and ice grains. It is important to characterize hydrated PAHs and their
      cations to explore their stability in interstellar and biological media. Herein,
      the infrared photodissociation (IRPD) spectrum of the naphthalene+-H2O radical
      cation (Np+-H2O) recorded in the O-H and C-H stretch range is analysed by
      dispersion-corrected density functional theory calculations at the B3LYP-D3/aug
      cc-pVTZ level to determine its structure and intermolecular bonding.
      Monohydration of Np+ in its 2Au ground electronic state leads to the formation of
      a bifurcated CHO ionic hydrogen bond (H-bond), in which the lone pairs of H2O
      bind to two adjacent CH proton donors of the two aromatic rings. The frequency
      dependent branching ratios observed for IRPD of cold Np+-H2O-Ar clusters allows
      the estimation of the dissociation energy of Np+-H2O as D0 ~ 2800 +/- 300 cm-1.
      The monohydration motif of Np+ differs qualitatively from that of the benzene
      cation in both structure and binding energy, indicating the strong influence of
      the multiple aromatic rings on the hydration of PAH+ cations. This difference is
      rationalized by natural bond orbital analysis of the ionic H-bond motif.
      Comparison with neutral Np-H2O reveals the large change in structure and bond
      strength of the hydrated PAHs upon ionization. While neutral Np-H2O is stabilized
      by weak pi H-bonds (OHpi, pi-stacking), strong cation-dipole forces favour a
      planar bifurcated CHO ionic H-bond in Np+-H2O.

PMID- 29192904
TI  - Specific substrate-driven changes in human faecal microbiota composition contrast
      with functional redundancy in short-chain fatty acid production.
AB  - The diet provides carbohydrates that are non-digestible in the upper gut and are
      major carbon and energy sources for the microbial community in the lower
      intestine, supporting a complex metabolic network. Fermentation produces the
      short-chain fatty acids (SCFAs) acetate, propionate and butyrate, which have
      health-promoting effects for the human host. Here we investigated microbial
      community changes and SCFA production during in vitro batch incubations of 15
      different non-digestible carbohydrates, at two initial pH values with faecal
      microbiota from three different human donors. To investigate temporal stability
      and reproducibility, a further experiment was performed 1 year later with four of
      the carbohydrates. The lower pH (5.5) led to higher butyrate and the higher pH
      (6.5) to more propionate production. The strongest propionigenic effect was found
      with rhamnose, followed by galactomannans, whereas fructans and several alpha-
      and beta-glucans led to higher butyrate production. 16S ribosomal RNA gene-based
      quantitative PCR analysis of 22 different microbial groups together with 454
      sequencing revealed significant stimulation of specific bacteria in response to
      particular carbohydrates. Some changes were ascribed to metabolite cross-feeding,
      for example, utilisation by Eubacterium hallii of 1,2-propanediol produced from
      fermentation of rhamnose by Blautia spp. Despite marked inter-individual
      differences in microbiota composition, SCFA production was surprisingly
      reproducible for different carbohydrates, indicating a level of functional
      redundancy. Interestingly, butyrate formation was influenced not only by the
      overall % butyrate-producing bacteria in the community but also by the initial
      pH, consistent with a pH-dependent shift in the stoichiometry of butyrate
      production.

PMID- 29192905
TI  - Microbial life on a sand grain: from bulk sediment to single grains.
AB  - Globally, marine surface sediments constitute a habitat for estimated 1.7 * 1028
      prokaryotes. For benthic microbial community analysis, usually, several grams of
      sediment are processed. In this study, we made the step from bulk sediments to
      single sand grains to address the microbial community directly in its micro
      habitat: the individual bacterial diversity on 17 sand grains was analyzed by 16S
      ribosomal RNA gene sequencing and visualized on sand grains using catalyzed
      reporter deposition fluorescence in situ hybridization. In all, 104-105 cells
      were present on grains from 202 to 635 MUm diameter. Colonization was patchy,
      with exposed areas largely devoid of any epi-growth (mean cell-cell distance
      4.5+/-5.9 MUm) and protected areas more densely populated (0.5+/-0.7 MUm). Mean
      cell-cell distances were 100-fold shorter compared with the water column. In
      general, growth occurred in monolayers. Each sand grain harbors a highly diverse
      bacterial community as shown by several thousand species-level operational
      taxonomic units (OTU)0.97. Only 4-8 single grains are needed to cover 50% of
      OTU0.97 richness found in bulk sediment. Although bacterial communities differed
      between sand grains, a core community accounting for >50% of all cells was
      present on each sand grain. The communities between sediment grains are more
      similar than between soil macroaggregates.

PMID- 29192907
TI  - Theoretical identification of seven C80 fullerene isomers by XPS and NEXAFS
      spectroscopy.
AB  - The carbon K-shell (1s) X-ray photoelectron spectroscopy (XPS) and near-edge X
      ray absorption fine structure (NEXAFS) spectroscopy of the seven isolated
      pentagon-rule (IPR) isomers of fullerene C80 have been calculated by means of
      density functional theory (DFT) theoretically. We have demonstrated the
      relationship between molecular structures and related X-ray spectroscopies. The
      dependence of the XPS spectra on the structures of the seven C80 molecules is
      imperfect, while the NEXAFS spectra show strong dependence on the seven fullerene
      molecules, so the NEXAFS spectra can be employed to identify all of the studied
      isomers. The spectral components of different local environments have been
      explored in detail.

PMID- 29192909
TI  - The silane-methane dimer revisited: more than a dispersion-bound system?
AB  - We present here a comprehensive computational and theoretical analysis of the
      silane-methane dimer with the goal of understanding the origin of the
      interactions that hold it together and the factors that affect its strength.
      Several interaction topologies have been analysed and the associated interaction
      energies have been evaluated at the CCSD(T)/aug-cc-pVTZ level of theory. Next,
      substitution effects have been studied on several silane and methane derivatives.
      The molecular electrostatic potential (MEP) maps of the molecules involved in the
      interactions have been built to try to correlate the interaction energies with
      the maximum/minimum EP values (Vs). Furthermore, we have performed an energy
      decomposition analysis to gain deeper insight into the physical nature of the
      interactions and to unravel whether dispersion is the primary component of the
      attraction. Finally, we complete the theoretical analysis with the study of
      several experimental crystal structures in which there are silylmethyl short
      contacts.

PMID- 29192908
TI  - A spectroscopic study on the satellite vibronic band in phosphorescent Pt
      complexes with high colour purity.
AB  - To understand the relationship between the narrowing of an emission band and
      structural changes, we synthesised tetradentate Pt-complexes. Pt-1 has two
      directly connected carbazole (Cz) moieties, Pt-2 has two additional methyl groups
      to Pt-1, and Pt-3 has one Cz moiety. The absorption and emission spectra of Pt-2
      were identical to those of Pt-1. Pt-3's emission was observed at a shorter
      wavelength compared to the others. We achieved phosphorescence with high colour
      purity by introducing a tetradentate ligand. All the Pt-complexes showed a
      vibronic structure in the emission spectra measured at 77 and 300 K. The 0-0
      vibronic band of the Pt-complexes is quite intense compared to the 0-1 vibronic
      band, which may be due to less structural change of the fused tetradentate ligand
      in the excited state relative to the ground state. The spacing of the 0-0 and 1-0
      vibronic bands is 1487 and 1323 cm-1, respectively. To understand the origin of
      the satellite vibronic bands, we carried out vibrational spectroscopic (IR and
      Raman) measurements and theoretical calculations to analyse the infrared
      spectrum. In addition, we carried out a transient Raman experiment to obtain the
      vibronic information of an excited Pt-1. The vibronic spacing in the emission was
      caused by the displacement of the potential energy curve in the excited state.
      The highest occupied molecular orbital is populated with a Cz moiety and the
      lowest unoccupied molecular orbital is localized at the terminal pyridine moiety.
      For the triplet state, however, the highest singly occupied molecular orbital is
      delocalized on the pyrazole or imidazole moiety, as well as the pyridine moiety.
      These groups are located at the terminal site of the ligand, and are less
      rigidified and more flexible. Therefore, the major origin of the satellite
      vibration band in emission spectra is the stretching of the terminal groups.

PMID- 29192910
TI  - Combined determination of copper ions and beta-amyloid peptide by a single
      ratiometric electrochemical biosensor.
AB  - Copper ions (Cu2+) play a critical role in biological processes and are directly
      involved in beta-amyloid peptide (Abeta) aggregation, which is responsible for
      the occurrence and development of Alzheimer's disease (AD). Therefore, combined
      determination of Cu2+ and Abeta in one analytical system is of great significance
      to understand the exact nature of the AD event. This work presents a novel
      ratiometric electrochemical biosensor for the dual determination of Cu2+ and
      Abeta1-42. This unique sensor is based on a 2,2'-azinobis-(3-ethylbenzothiazoline
      6-sulphonate) (ABTS) and poly(diallyldimethylammonium chloride) (PDDA)-bi
      functionalized single-walled carbon nanotubes (ABTS-PDDA/CNTs) composite. The
      inclusion of ABTS not only enhanced the sensitivity, but it also acted as an
      inner reference molecule to improve detection accuracy. The specific recognition
      of Cu2+ was realized by neurokinin B (NKB) coatings on the ABTS-PDDA/CNTs surface
      to form a [CuII(NKB)2] complex with Cu2+. The ABTS-PDDA/CNTs-NKB modified
      electrode also displayed an excellent electrochemical response toward the Abeta1
      42 monomer, when a certain amount of the Abeta1-42 monomer was added to Cu2+
      contained PBS buffer, which was due to the release of Cu2+ from the [CuII(NKB)2]
      complex through Abeta binding to Cu2+. Meanwhile, our work showed that Cu2+ bound
      Abeta1-42 was concentration-dependent. Consequently, the presented
      electrochemical approach was capable of quantifying two important biological
      species associated with AD by one single biosensor, with the detection limits of
      0.04 MUM for Cu2+ and 0.5 ng mL-1 for Abeta1-42, respectively. Finally, the
      ratiometric electrode was successfully applied for monitoring Cu2+ and Abeta1-42
      variations in plasma and hippocampus of normal and AD rats.

PMID- 29192911
TI  - Reversible switching of the spin state in a manganese phthalocyanine molecule by
      atomic nitrogen.
AB  - Reversible control of the spin state of an organic molecule is significant for
      the development of molecular spintronic devices. Here, density functional theory
      calculations have been performed to study the adsorption of atomic nitrogen on a
      single manganese phthalocyanine (MnPc) molecule, three-layered MnPc, and MnPc on
      an Fe(100) surface. For all three cases, the N atom strongly adsorbs on top of
      the Mn atom and induces a significant variation of the geometric, electronic and
      magnetic properties. After N adsorption, an energy gap appears and the electronic
      states become unpolarized. Different functionals including three hybrid
      functionals are used in these calculations, and all yield a switchable spin
      state.

PMID- 29192912
TI  - Quantitative profiling of carbonyl metabolites directly in crude biological
      extracts using chemoselective tagging and nanoESI-FTMS.
AB  - The extensive range of chemical structures, wide range of abundances, and
      chemical instability of metabolites present in the metabolome pose major
      analytical challenges that are difficult to address with existing technologies.
      To address these issues, one approach is to target a subset of metabolites that
      share a functional group, such as ketones and aldehydes, using chemoselective
      tagging. Here we report a greatly improved chemoselective method for the
      quantitative analysis of hydrophilic and hydrophobic carbonyl-containing
      metabolites directly in biological samples. This method is based on direct tissue
      or cells extraction with simultaneous derivatization of stable and labile
      carbonylated metabolites using N-[2-(aminooxy)ethyl]-N,N-dimethyl-1
      dodecylammonium (QDA) and 13CD3 labeled QDA. We combined innovations of direct
      quenching of biological sample with frozen derivatization conditions under the
      catalyst N,N-dimethyl-p-phenylenediamine, which facilitated the formation of
      oxime stable-isotope ion pairs differing by m/z 4.02188 while minimizing
      metabolite degradation. The resulting oximes were extracted by HyperSep C8 tips
      to remove interfering compounds, and the products were detected using nano
      electrospray ionization interfaced with a Thermo Fusion mass spectrometer. The
      quaternary ammonium tagging greatly increased electrospray MS detection
      sensitivity and the signature ions pairs enabled simple identification of
      carbonyl compounds. The improved method showed the lower limits of quantification
      for carbonyl standards to be in the range of 0.20-2 nM, with linearity of R2 >
      0.99 over 4 orders of magnitude. We have applied the method to assign 66
      carbonyls in mouse tumor tissues, many of which could not be assigned solely by
      accurate mass and tandem MS. Fourteen of the metabolites were quantified using
      authentic standards. We also demonstrated the suitability of this method for
      determining 13C labeled isotopologues of carbonyl metabolites in 13C6-glucose
      based stable isotope-resolved metabolomic (SIRM) studies.

PMID- 29192913
TI  - Cu/Pd cooperatively catalyzed tandem intramolecular anti-Markovnikov
      hydroarylation of unsaturated amides: facile construction of 3,4
      dihydroquinolinones via borylation/intramolecular C(sp3)-C(sp2) cross coupling.
AB  - An anti-Markovnikov hydroarylation of unsaturated amides via a Cu/Pd
      synergistically catalyzed cascade borylation/intramolecular sp2-sp3 cross
      coupling has been disclosed. 3,4-Dihydroquinolinones, one type of important
      scaffold prevailing in pharmaceuticals and biologically active compounds, could
      be readily accessible with high regio-selectivity and high yields.

PMID- 29192914
TI  - Ab initio analysis on potential superbases of several hyperlithiated species:
      Li3F2O and Li3F2OHn (n = 1, 2).
AB  - A systematic investigation on the potential basicity of the novel hyperlithiated
      species Li3F2O and Li3F2(OH)n (n = 1, 2) based upon the superalkali cluster Li3F2
      was conducted using high-level ab initio techniques. Equilibrium structures for
      both the neutral and anionic states in the gas-phase were identified and their
      relative stabilities using atomization enthalpies are analysed and compared with
      their respective proton affinities and gas-phase basicities. Our calculations,
      using a modified form of the CBS-QB3 composite method, identified several unique
      structures that possess superbase potential comparable to the proton affinity of
      Roger Alder's canonical Proton Sponge. The calculations show that, in general, as
      the number of hydroxide groups increase, so too does the proton affinity.

PMID- 29192915
TI  - Observation of A Raman mode splitting in few layer black phosphorus encapsulated
      with hexagonal boron nitride.
AB  - We investigate the impact of encapsulation with hexagonal boron nitride (h-BN) on
      the Raman spectrum of few layer black phosphorus. The encapsulation results in a
      significant reduction of the line width of the Raman modes of black phosphorus,
      due to a reduced phonon scattering rate. We observe a so far elusive peak in the
      Raman spectra ~4 cm-1 above the A mode in trilayer and thicker flakes, which had
      not been observed experimentally. The newly observed mode originates from the
      strong black phosphorus inter-layer interaction, which induces a hardening of the
      surface atom vibration with respect to the corresponding modes of the inner
      layers. The observation of this mode suggests a significant impact of h-BN
      encapsulation on the properties of black phosphorus and can serve as an indicator
      of the quality of its surface.

PMID- 29192916
TI  - Theoretical investigation of the impact of ligands on the regiodivergent Rh
      catalyzed hydrothiolation of allyl amines.
AB  - The reaction mechanisms of the Rh-catalyzed regiodivergent hydrothiolation of
      allyl amines have been theoretically investigated with the aid of density
      functional theory (DFT) calculations. The impact of ligands on the
      regioselectivity was rationalized. The origin of the regioselectivity involved in
      these reactions was probed by investigating the electronic and steric effects.
      The regioselectivity is derived from the stability of related intermediates.
      Among them, the steric effect plays an important role in controlling the
      regioselectivity. The origin of the regioselectivity could also be interpreted
      through the electronic effect on the corresponding transition states.

PMID- 29192917
TI  - Unexpected catalytic performance of Fe-M-C (M = N, P, and S) electrocatalysts
      towards oxygen reduction reaction: surface heteroatoms boost the activity of
      Fe2M/graphene nanocomposites.
AB  - The rational design of non-noble materials as low-cost, highly efficient, and
      durable catalysts to improve the oxygen reduction reaction is extremely urgent
      and challenging. The oxygen reduction reaction is a kinetically sluggish process
      that greatly affects the energy conversion efficiency. In this paper, novel
      hierarchical heteroatoms-co-doped Fe2M/graphene (M = P, N) nanocomposites were
      developed by a facile strategy, including hydrothermal and subsequent calcination
      methods. The thermal treatment of an ionic liquid and thiourea not only supplied
      heteroatom sources but also promoted the formation of iron phosphide and iron
      nitride and enhanced their catalytic performances. The electrochemical results
      indicated that the as-obtained hybrid catalysts manifested enhanced
      electrocatalytic activity toward the oxygen reduction reaction owing to the
      strong synergistic effects. The high content of heteroatoms distributed on the
      surface and interface of the hybrids and the density functional theory
      calculations suggested that Fe-N-C, Fe-P-C, and Fe-S-C multiple active surface
      sites were formed at the hybrids interfaces. Moreover, these results demonstrated
      that heteroatom-doped catalysts could effectively form a charge-transfer channel
      and thus modify the charge distribution in the hybrids interfaces. The as
      prepared heteroatoms-doped Fe2M/graphene hybrids would be developed into highly
      efficient catalysts as ideal alternatives for noble metal catalysts in practical
      applications.

PMID- 29192918
TI  - External oxidant-free cross-coupling: electrochemically induced aromatic C-H
      phosphonation of azoles with dialkyl-H-phosphonates under silver catalysis.
AB  - A convenient external oxidant-free method of phosphorylation of azole derivatives
      (benzo-1,3-azoles, 3-methylindole, 4-methyl-2-acetylthiazole) by using dialkyl-H
      phosphonates through the catalytic oxidation of their mixture under
      electrochemical mild conditions (room temperature, normal pressure) in the
      presence of silver salts or oxide (1%) is proposed. This method allows us to
      obtain the desired azole dialkylphosphonates with good yield (up to 75%). The
      transformations of silver and phosphorus precursors and intermediates using
      cyclic voltammetry, ESR, and NMR spectroscopy were investigated, and a radical
      process mechanism was proposed. It has been found that AgP(O)(OEt)2 is oxidized
      earlier than other components of the reaction mixture with the elimination of a
      radical. The ESR spectrum of this radical's adduct was obtained in the presence
      of the radical trap PBN. Ag2+ is out of the catalytic cycle.

PMID- 29192919
TI  - Oxidative stress-induced increase of intracellular zinc in astrocytes decreases
      their functional expression of P2X7 receptors and engulfing activity.
AB  - Neuron-glia communication mediated by neuro- and glio-transmitters such as ATP
      and zinc is crucial for the maintenance of brain homeostasis, and its
      dysregulation is found under pathological conditions. It is reported that under
      oxidative stress-loaded conditions, astrocytes exhibit increased intra- and extra
      cellular labile zinc, the latter triggering microglial M1 activation, while the
      pathophysiological role of the former remains unrevealed. In this study, we
      examined whether the oxidative stress-induced increase of intracellular labile
      zinc is involved in the P2X7 receptor (P2X7R)-mediated regulation of astrocytic
      engulfing activity. The exposure of cultured astrocytes to sub-lethal oxidative
      stress through their treatment with 400 MUM H2O2 increased intracellular labile
      zinc, of which the concentration reached a peak level of approximately 2 MUM at 2
      h after the treatment. In astrocytes under sub-lethal oxidative stress, the
      uptake of YO-PRO-1 and latex beads as markers for P2X7R channel/pore activity and
      astrocytic engulfing activity, respectively, was decreased, and these decreased
      activities were accompanied by decreased expression of P2X7R at the plasma
      membrane via intracellular labile zinc-mediated translocation of it. With the
      oxidative stress, the expression level of full length P2X7R relative to that of
      its splice variants in astrocytes was decreased, leading to a decrease of the
      relative expression of the trimer consisting of full length P2X7R. Collectively,
      sub-lethal oxidative stress induces an astrocytic modal shift from the normal
      resting engulfing mode to the activated astrogliosis mode via an intracellular
      labile zinc-mediated decrease of the functional expression of P2X7R.

PMID- 29192920
TI  - In situ characterization of advanced glycation end products (AGEs) in collagen
      and model extracellular matrix by solid state NMR.
AB  - Non-enzymatic glycation of extracellular matrix with (U-13C5)-d-ribose-5
      phosphate (R5P), enables in situ 2D ssNMR identification of many deleterious
      protein modifications and crosslinks, including previously unreported oxalamido
      and hemiaminal (CH3-CH(OH)NHR) substructures. Changes in charged residue
      proportions and distribution may be as important as crosslinking in provoking and
      understanding harmful tissue changes.

PMID- 29192921
TI  - Escape of anions from geminate recombination in THF due to charge delocalization.
AB  - Geminate recombination of 24 radical anions (M-) with solvated protons (RH2+) was
      studied in tetrahydrofuran (THF) with pulse radiolysis. The recombination has two
      steps: (1) diffusion of M- and RH2+ together to form intimate (contact and
      solvent separated) ion pairs, driven by Coulomb attraction; (2) annihilation of
      anions due to proton transfer (PT) from RH2+ to M-. The non-exponential time
      dependence of the geminate diffusion was determined. For all molecules protonated
      on O or N atoms the subsequent PT step is too fast (<0.2 ns) to measure, except
      for the anion of TCNE which did not undergo proton transfer. PT to C atoms was as
      slow as 70 ns and was always slow enough to be observable. A possible effect of
      charge delocalization on the PT rates could not be clearly separated from other
      factors. For 21 of the 24 molecules studied here, a free ion yield (71.6 +/- 6.2
      nmol J-1) comprising ~29% of the total, was formed. This yield of "Type I" free
      ions is independent of the PT rate because it arises entirely by escape from the
      initial distribution of ion pair distances without forming intimate ion pairs.
      Three anions of oligo(9,9-dihexyl)fluorenes, Fn- (n = 2-4) were able to escape
      from intimate ion-pairs to form additional yields of "Type II" free ions with
      escape rate constants near 3 * 106 s-1. These experiments find no evidence for an
      inverted region for proton transfer.

PMID- 29192922
TI  - Novel penta-graphene nanotubes: strain-induced structural and semiconductor-metal
      transitions.
AB  - Research into novel one-dimensional (1D) materials and associated structural
      transitions is of significant scientific interest. It is widely accepted that a
      1D system with a short-range interaction cannot have 1D phase transition at
      finite temperature. Herein, we propose a series of new stable carbon nanotubes by
      rolling up penta-graphene sheets, which exhibit fascinating well-defined 1D phase
      transitions triggered by axial strain. Our first-principles calculations show
      that such penta-graphene nanotubes (PGNTs) are dynamically stable by phonon
      calculations, but transform from a tri-layer structure to a highly defective
      single-walled nanotube at low temperature in molecular dynamics simulations. We
      show that moderate compressive strains can drive structural transitions of (4,4),
      (5,5), and (6,6) PGNTs, during which the distances of neighboring carbon dimers
      in the inner shell have a sudden drop, corresponding to dimer-dimer nonbonding to
      bonding transitions. After such transition, the tubes become much more thermally
      stable and undergo semiconductor-metal transitions under increasing strain. The
      band gaps of PGNTs are not sensitive to chirality whereas they can be tuned
      effectively from visible to short-wavelength infrared by appropriate strain,
      making them appealing materials for flexible nano-optoelectronics. These findings
      provide useful insight into unusual phase transitions in low-dimensional systems.

PMID- 29192923
TI  - Electron beam induced tunneling magnetoresistance in spatially confined manganite
      bridges.
AB  - Certain manganites exhibit rich and technologically relevant transport properties
      which can often be attributed to the existence and changes of the intrinsic
      electronic phase competition within these materials. Here we demonstrate that a
      scanning electron beam can be used to artificially create domain configurations
      within La0.3Pr0.4Ca0.3MnO3 thin film microbridges that results in novel magneto
      transport effects. In particular, the electron beam preferentially produces
      insulating regions within the narrow film and can be used to create a
      configuration consisting of ferromagnetic metallic domains separated by a
      potential barrier. This arrangement enables the spin-dependent tunneling of
      charge carriers and can produce large switching tunneling magnetoresistance
      effects which were initially absent. Hence, this work describes a new and
      potentially powerful method for engineering the electronic phase domains in
      manganites to generate functional transport properties that are important for
      spintronic devices.

PMID- 29192924
TI  - NiMn2O4 spinel binary nanostructure decorated on three-dimensional reduced
      graphene oxide hydrogel for bifunctional materials in non-enzymatic glucose
      sensor.
AB  - Nickel-manganese spinel oxide (NiMn2O4) was hybridized with reduced graphene
      oxide hydrogel (rGOH) via a facile solvothermal process and a highly porous three
      dimensional (3D) structure was constructed. NiMn2O4/rGOH exhibited excellent
      electrochemical performance due to the high specific surface area, excellent
      electrocatalytic activity, and enhanced electrical conductivity due to the
      synergetic effects between the two components. The NiMn2O4/rGOH exhibited
      excellent glucose sensing performance with high sensitivity (1310.8 MUA mM-1 cm
      2), a wide linear range (2 MUM-20 mM), rapid response time (<3.5 s), and anti
      interference properties. Furthermore, it also showed excellent supercapacitor
      performance with a high capacitance (396.85 F g-1) and excellent energy and power
      density on account of the large surface area and pseudo-capacitor behavior of
      NiMn2O4. A self-powered glucose sensor can be fabricated with NiMn2O4/rGOH as
      both supercapacitor and glucose sensing electrodes.

PMID- 29192925
TI  - Work function and temperature dependence of electron tunneling through an N-type
      perylene diimide molecular junction with isocyanide surface linkers.
AB  - Conducting probe atomic force microscopy (CP-AFM) was employed to examine
      electron tunneling in self-assembled monolayer (SAM) junctions. A 2.3 nm long
      perylene tetracarboxylic acid diimide (PDI) acceptor molecule equipped with
      isocyanide linker groups was synthesized, adsorbed onto Ag, Au and Pt substrates,
      and the current-voltage (I-V) properties were measured by CP-AFM. The dependence
      of the low-bias resistance (R) on contact work function indicates that transport
      is LUMO-assisted ('n-type behavior'). A single-level tunneling model combined
      with transition voltage spectroscopy (TVS) was employed to analyze the
      experimental I-V curves and to extract the effective LUMO position epsilonl =
      ELUMO - EF and the effective electronic coupling (Gamma) between the PDI redox
      core and the contacts. This analysis revealed a strong Fermi level (EF) pinning
      effect in all the junctions, likely due to interface dipoles that significantly
      increased with increasing contact work function, as revealed by scanning Kelvin
      probe microscopy (SKPM). Furthermore, the temperature (T) dependence of R was
      found to be substantial. For Pt/Pt junctions, R varied more than two orders of
      magnitude in the range 248 K < T < 338 K. Importantly, the R(T) data are
      consistent with a single step electron tunneling mechanism and allow independent
      determination of epsilonl, giving values compatible with estimates of epsilonl
      based on analysis of the full I-V data. Theoretical analysis revealed a general
      criterion to unambiguously rule out a two-step transport mechanism: namely, if
      measured resistance data exhibit a pronounced Arrhenius-type temperature
      dependence, a two-step electron transfer scenario should be excluded in cases
      where the activation energy depends on contact metallurgy. Overall, our results
      indicate (1) the generality of the Fermi level pinning phenomenon in molecular
      junctions, (2) the utility of employing the single level tunneling model for
      determining essential electronic structure parameters (epsilonl and Gamma), and
      (3) the importance of changing the nature of the contacts to verify transport
      mechanisms.

PMID- 29192926
TI  - On-chip label-free protein analysis with downstream electrodes for direct removal
      of electrolysis products.
AB  - The ability to apply highly controlled electric fields within microfluidic
      devices is valuable as a basis for preparative and analytical processes. A
      challenge encountered in the context of such approaches in conductive media,
      including aqueous buffers, is the generation of electrolysis products at the
      electrode/liquid interface which can lead to contamination, perturb fluid flows
      and generally interfere with the measurement process. Here, we address this
      challenge by designing a single layer microfluidic device architecture where the
      electric potential is applied outside and downstream of the microfluidic device
      while the field is propagated back to the chip via the use of a co-flowing highly
      conductive electrolyte solution that forms a stable interface at the separation
      region of the device. The co-flowing electrolyte ensures that all the generated
      electrolysis products, including Joule heat and gaseous products, are flowed away
      from the chip without coming into contact with the analytes while the single
      layer fabrication process where all the structures are defined lithographically
      allows producing the devices in a simple yet highly reproducible manner. We
      demonstrate that by allowing stable and effective application of electric fields
      in excess of 100 V cm-1, the described platform provides the basis for rapid
      separation of heterogeneous mixtures of proteins and protein complexes directly
      in their native buffers as well as for the simultaneous quantification of their
      charge states. We illustrate this by probing the interactions in a mixture of an
      amyloid forming protein, amyloid-beta, and a molecular chaperone, Brichos, known
      to inhibit the process of amyloid formation. The availability of a platform for
      applying stable electric fields and its compatibility with single-layer soft
      lithography processes opens up the possibility of separating and analysing a wide
      range of molecules on chip, including those with similar electrophoretic
      mobilities.

PMID- 29192927
TI  - High-nuclear heterometallic oxime clusters assembled from triangular subunits:
      solvothermal syntheses, crystal structures and magnetic properties.
AB  - Three series of six pyrazine-2-amidoxime (H2pzaox)-based 3d-4f clusters,
      {Ln8Ni6}, {Ln5Ni10} and {Ln5Ni8} (Ln = Dy and Gd), were solvothermally
      synthesized in the absence or presence of different coligands, and were
      structurally and magnetically characterized. The unusual ring-shaped {Ln8(MU3
      OH)4} core in the two {Ln8Ni6} complexes is generated by four corner-sharing
      triangle {Ln3(MU3-OH)} units, which are further connected to six outer NiII ions
      by twelve deprotonated H2pzaox ligands in three common binding modes. By
      contrast, the remaining four clusters contain only two corner-sharing {Ln3(MU3
      OH)} triangles, which interact with peripheral NiII ions through fourteen H2pzaox
      ligands in five (for {Ln5Ni10}) and four (for {Ln5Ni8}) different bridging ways.
      Thus, the interesting core motifs observed in these clusters depend significantly
      on the number of the triangular {Ln3(MU3-OH)} subunits and their connectivity
      manner with the singly and doubly deprotonated pyrazine-2-amidoxime ligand.
      Additionally, weak ferromagnetic superexchange in the {Dy5Ni10} and {Ln5Ni8}
      clusters and antiferromagnetic coupling in {Ln8Ni6} and {Gd5Ni10} clusters was
      respectively mediated by versatile oximate bridges between the intramolecular
      LnIII and NiII ions. Furthermore, the three DyIII-derived aggregates exhibit
      slightly temperature-dependent magnetic relaxations under a zero dc field, and
      the three GdIII-based clusters display large magnetic entropy changes of 23.5 J
      kg-1 K-1 for {Gd8Ni6}, 19.4 J kg-1 K-1 for {Gd5Ni10}, and 22.4 J kg-1 K-1 for
      {Ln5Ni8} at 4.0 K and 70 kOe. These interesting results are helpful for the
      understanding of oximate-based 3d-4f coordination chemistry and their structure
      function relationships.

PMID- 29192928
TI  - Synthesis of 2-methylbenzoxazoles directly from N-phenylacetamides catalyzed by
      palladium acetate.
AB  - A method to synthesize 2-methylbenzoxazoles directly from N-phenylacetamides
      catalyzed by Pd(OAc)2 in the presence of K2S2O8 and TfOH has been developed. The
      desired products were obtained in moderate to excellent yields. This approach
      provides a facile procedure to prepare benzoxazoles with available substrates. It
      is found that TfOH is the key factor for this cyclization reaction. A plausible
      mechanism of the reaction is proposed according to the control reactions and the
      literature.

PMID- 29192929
TI  - Viscoelastic flow past mono- and bidisperse random arrays of cylinders: flow
      resistance, topology and normal stress distribution.
AB  - We investigate creeping viscoelastic fluid flow through two-dimensional porous
      media consisting of random arrangements of monodisperse and bidisperse cylinders,
      using our finite volume-immersed boundary method introduced in S. De, et al., J.
      Non-Newtonian Fluid Mech., 2016, 232, 67-76. The viscoelastic fluid is modeled
      with a FENE-P model. The simulations show an increased flow resistance with
      increase in flow rate, even though the bulk response of the fluid to shear flow
      is shear thinning. We show that if the square root of the permeability is chosen
      as the characteristic length scale in the determination of the dimensionless
      Deborah number (De), then all flow resistance curves collapse to a single master
      curve, irrespective of the pore geometry. Our study reveals how viscoelastic
      stresses and flow topologies (rotation, shear and extension) are distributed
      through the porous media, and how they evolve with increasing De. We correlate
      the local viscoelastic first normal stress differences with the local flow
      topology and show that the largest normal stress differences are located in shear
      flow dominated regions and not in extensional flow dominated regions at higher
      viscoelasticity. The study shows that normal stress differences in shear flow
      regions may play a crucial role in the increase of flow resistance for
      viscoelastic flow through such porous media.

PMID- 29192930
TI  - Simple peptide coacervates adapted for rapid pressure-sensitive wet adhesion.
AB  - We report here that a dense liquid formed by spontaneous condensation, also known
      as simple coacervation, of a single mussel foot protein-3S-mimicking peptide
      exhibits properties critical for underwater adhesion. A structurally homogeneous
      coacervate is deposited on underwater surfaces as micrometer-thick layers, and,
      after compression, displays orders of magnitude higher underwater adhesion at 2 N
      m-1 than that reported from thin films of the most adhesive mussel-foot-derived
      peptides or their synthetic mimics. The increase in adhesion efficiency does not
      require nor rely on post-deposition curing or chemical processing, but rather
      represents an intrinsic physical property of the single-component coacervate. Its
      wet adhesive and rheological properties correlate with significant dehydration,
      tight peptide packing and restriction in peptide mobility. We suggest that such
      dense coacervate liquids represent an essential adaptation for the initial
      priming stages of mussel adhesive deposition, and provide a hitherto untapped
      design principle for synthetic underwater adhesives.

PMID- 29192931
TI  - Homo- and copolymerization of norbornene with tridentate nickel complexes bearing
      o-aryloxide-N-heterocyclic carbene ligands.
AB  - A series of new pincer-type tridentate o-aryloxide-N-heterocyclic carbene nickel
      complexes Ni1-Ni3 were synthesized, and the molecular structure of Ni3 was
      confirmed by X-ray crystallography. In comparison with the above tridentate
      complexes, the bidentate bis(aryloxide-NHC) nickel complex Ni4 was also
      synthesized. On activation with either Et2AlCl or Me2AlCl, all nickel complexes
      showed low activity toward norbornene (NB) homopolymerization. Surprisingly, Ni1
      Ni3 catalysts exhibited moderate to high activity toward the homopolymerization
      (up to 3.21 * 106 g PNB (mol of Ni)-1 h-1) and copolymerization of norbornene
      with 1-octene (up to 1.39 * 105 g polymer (mol of Ni)-1 h-1) with B(C6F5)3 as the
      cocatalyst even at 100  degrees C, showing that tridentate nickel catalysts have
      high thermal stability. Notably, the tridentate Ni1-Ni3 complexes showed better
      activities than the corresponding bidentate bis(aryloxide-NHC) nickel complex
      Ni4. The obtained poly(NB-co-1-octene)s were confirmed to be vinyl-addition
      copolymers, which exhibited high 1-octene insertion ratio (9%-17%), good thermal
      stability (Td > 400  degrees C), high molecular weight (up to 105), and narrow
      molecular weight distribution (PDI <= 1.91).

PMID- 29192932
TI  - A Novel Technique to Repair Acute and Chronic Proximal Hamstring Avulsions.
AB  - Treatment of proximal hamstring avulsions is challenging regarding both timing
      and choice of repair. In chronic situations, the tissue can become attenuated,
      bringing into question the need for adjunctive allograft. In general, proximal
      hamstring avulsions are affixed back to the ischial tuberosity with suture
      anchors, with allograft used as needed for chronic situations. This article
      reports on a novel technique of suspensory fixation with a unicortical button but
      without allograft to repair both acute and chronic proximal hamstring avulsions.
      Three patients, all of whom regained full strength and functionality 1 year
      postoperatively, are described. [Orthopedics. 2018; 41(2):116-119.].

PMID- 29192933
TI  - Short-term Outcomes of Total Knee Arthroplasty Performed at an Orthopedic
      Specialty Hospital.
AB  - This study compared perioperative outcomes for total knee arthroplasty (TKA) at
      an orthopedic specialty hospital and a tertiary referral center. The authors
      identified all primary TKA procedures performed in 2014 at the 2 facilities. Each
      patient at the orthopedic specialty hospital was manually matched to a patient at
      the tertiary referral center according to demographic and clinical variables.
      Matching was blinded to outcomes. Outcomes were 90-day readmission, mortality
      rate, reoperation, length of stay, and use of inpatient rehabilitation. Each
      group had 215 TKA patients. The 2 groups of patients were similar in age (66.8
      years, P=.98), body mass index (30.4 kg/m2, P=.99), age-adjusted Charlson
      Comorbidity Index (3.4, P=1.00), and sex (46.0% male, P=1.00). Mean length of
      stay was 1.47+/-0.62 days at the orthopedic specialty hospital vs 1.87+/-0.75
      days (P<.01) at the tertiary referral center. There were 3 readmissions at the
      orthopedic specialty hospital and 6 readmissions at the tertiary referral center
      (P=.31). There were 6 reoperations at the orthopedic specialty hospital and 5 at
      the tertiary referral center (P=.76). In addition, 8 patients at the orthopedic
      specialty hospital used inpatient rehabilitation vs 15 patients at the tertiary
      referral center (P=.08). One patient who was treated at the orthopedic specialty
      hospital required transfer to a tertiary referral center. This study found that
      perioperative outcomes were similar for matched patients who underwent primary
      TKA at an orthopedic specialty hospital and a tertiary referral center. Patients
      treated at the orthopedic specialty hospital spent 0.4 fewer days in the hospital
      compared with matched patients who were treated at the tertiary referral center.
      This equals 2 fewer hospital nights for every 5 TKA patients. [Orthopedics. 2018;
      41(1):e84-e91.].

PMID- 29192934
TI  - Predicting Injury in Professional Baseball Pitchers From Delivery Mechanics: A
      Statistical Model Using Quantitative Video Analysis.
AB  - Baseball pitching imposes significant stress on the upper extremity and can lead
      to injury. Many studies have attempted to predict injury through pitching
      mechanics, most of which have used laboratory setups that are often not practical
      for population-based analysis. This study sought to predict injury risk in
      professional baseball pitchers using a statistical model based on video analysis
      evaluating delivery mechanics in a large population. Career data were collected
      and video analysis was performed on a random sample of former and current
      professional pitchers. Delivery mechanics were analyzed using 6 categories: mass
      and momentum, arm swing, posture, position at foot strike, path of arm
      acceleration, and finish. Effects of demographics and delivery scores on injury
      were determined using a survival analysis, and model validity was assessed. A
      total of 449 professional pitchers were analyzed. Risk of injury significantly
      increased with later birth date, role as reliever vs starter, and previous major
      injury. Risk of injury significantly decreased with increase in overall delivery
      score (7.8%) and independently with increase in score of the mass and momentum
      (16.5%), arm swing (12.0%), and position at foot strike (22.8%) categories. The
      accuracy of the model in predicting injury was significantly better when
      including total delivery score compared with demographic factors alone. This
      study presents a model that evaluates delivery mechanics and predicts injury risk
      of professional pitchers based on video analysis and demographic variables. This
      model can be used to assess injury risk of professional pitchers and can be
      potentially expanded to assess injury risk in pitchers at other levels.
      [Orthopedics. 2018; 41(1):43-53.].

PMID- 29192935
TI  - Predictors of Persistent Pain After Fixation of Distal Clavicle Fractures in an
      Active Military Population.
AB  - Patients who undergo open reduction and internal fixation of distal clavicle
      fractures have a high rate of hardware removal and persistence of symptoms,
      particularly when attempting to return to high-demand activities. This study
      evaluated the outcomes of military servicemembers after surgical treatment of
      distal clavicle fractures. The authors performed a retrospective analysis of
      active duty servicemembers who underwent open reduction and internal fixation of
      Neer type II distal clavicle fractures between October 17, 2007, and July 20,
      2012, with a minimum of 2-year clinical follow-up. The electronic health record
      was queried to extract demographic features and clinical outcomes, primarily
      persistence of pain, removal of hardware, and postoperative return to high-level
      activity. A total of 48 patients were identified, with mean follow-up of 3.8
      years. A total of 44% of patients underwent subsequent hardware removal. All
      fractures achieved radiographic union, and 35% of patients had persistence of
      symptoms. Patients who were treated with hook plating had a 3.64-fold higher risk
      of persistence of pain compared with those treated with conventional plating
      techniques. A total of 35% of patients successfully returned to full military
      function and completed a postoperative military deployment. Coracoclavicular
      reconstruction did not improve outcomes. Persistence of symptoms and requirement
      for hardware removal were not associated with the rate of postoperative
      deployment. Achieving excellent functional outcomes with open reduction and
      internal fixation of distal clavicle fractures remains a challenge. Where
      possible, conventional plate fixation should be considered over hook plate
      fixation. However, subsequent hardware removal and continuing shoulder pain do
      not preclude a return to high-level activity. [Orthopedics. 2018; 41(1):e117
      e126.].

PMID- 29192936
TI  - Outcomes of Femoral Head Marrow Stimulation Techniques at Minimum 2-Year Follow
      up.
AB  - This study compared patients who underwent femoral head microfracture with a
      control group of patients who did not require microfracture. Patients had more
      than 2 years of follow-up. The patient groups had similar demographic and
      radiographic features, including sex, age within 5 years, body mass index within
      5 points, equal Tonnis grade, lateral center edge angle within 5 degrees , labral
      treatment, and capsular closure vs release. Inclusion criteria were a minimum of
      2 years of follow-up, Outerbridge grade IV cartilage damage, and femoral head
      marrow stimulation technique performed at the time of arthroscopy. Exclusion
      criteria were revision surgery, dysplasia, Tonnis grade of greater than 1,
      protrusio or profunda acetabuli, Perthes disease of the hip, slipped capital
      femoral epiphysis, abductor tear, and avascular necrosis of the hip. Patient
      reported outcomes included modified Harris hip score, nonarthritic hip score, hip
      outcome score-activity of daily living subscale, hip outcome score-sports
      subscale, and visual analog scale score for pain. Fifteen patients had femoral
      head microfracture with more than 2 years of follow-up. Mean improvements in
      modified Harris hip score, nonarthritic hip score, hip outcome score-sports
      subscale, and visual analog scale score were 17.1, 19.4, 30.5, and 2.8,
      respectively, for the microfracture group compared with 11.8, 18.5, 22.2, and
      3.0, respectively, for the control group. Both groups showed statistically
      significant improvement (P<.05) for all patient-reported outcomes, and no
      significant difference was found between the 2 patient groups at latest follow
      up. Two patients in the microfracture group vs 3 patients in the control required
      hip arthroplasty. Femoral head microfracture is a technically difficult
      procedure, but when performed correctly, the results are similar to those of
      patients who do not require microfracture. Further study of femoral head
      microfracture is necessary to confirm these encouraging short-term outcomes.
      [Orthopedics. 2018; 41(1):e70-e76.].

PMID- 29192937
TI  - Primary Total Hip Arthroplasty With Same-Day Discharge: Who Failed and Why.
AB  - As the emphasis on value-based care within total joint arthroplasty increases,
      this procedure is becoming more prevalent in the outpatient setting. The goals of
      this study were to report on the authors' early experiences with same-day
      discharge and to identify patient characteristics that are associated with
      failure to discharge after total hip arthroplasty within this program. All
      patients who were enrolled in the same-day discharge total hip arthroplasty
      program at the study institution between January 2015 and July 2016 were
      included. Demographics, baseline characteristics, and clinical and quality
      outcomes were compared between patients who successfully completed this program
      and those who did not. Of the 163 study subjects, 143 (87.7%) were discharged
      successfully on the same day as surgery. Women, patients younger than 40 years,
      and patients older than 60 years all had an increased risk of failing the
      program. Body mass index of 26 kg/m2 or less was associated with a 40% greater
      risk of failure. Patients with an American Society of Anesthesiologists score of
      3 had a 3-fold risk of failure compared with patients with an American Society of
      Anesthesiologists score of 2 or less. The screening protocol for same-day
      discharge at the study institution had an 87.7% rate of successful same-day
      discharge. Further investigation is needed to identify patients who are at risk
      of failing the same-day discharge initiative. [Orthopedics. 2018; 41(1):35-42.].

PMID- 29192938
TI  - [Editorial].

PMID- 29192939
TI  - [Lessons Learned from Experiencing Mavi At Cafe (Blue Horse Cafe) during Six
      Years: A Qualitative Analysis of Factors Contributing to Recovery from the
      Perspective of Schizophrenia Patients].
AB  - OBJECTIVE: In recent years, the recovery-oriented approaches (along with
      experiences and thoughts of patients and patient's relatives) have been taken
      into account for establishing mental health services and policies. This study
      aims to identify the factors contributing to recovery, as observed from the
      perspective of schizophrenia patients working at The Blue Horse Cafe which was
      founded by the Federation of Schizophrenia Associations. METHOD: The sample for
      the study consisted of 24 patients who worked at The Blue Horse Cafe. A
      phenomenological approach was used in the study, whereby interviews with patients
      were analyzed qualitatively. RESULTS: Certain common factors, which were
      expressed as having contributed to recovery, were identified from the perspective
      of schizophrenia patients. These factors are: 1-The fact that the setting is
      informal and welcoming without being constrictive; 2-Predominance of the human
      element; 3-Hope and encouragement; 4-Being cared about; 5-Being able to reach
      someone when in need of support; 6-Friendly sharing; 7-Having a purpose, assuming
      responsibility, and being motivated; and 8-Giving meaning to life. CONCLUSION:
      The findings may serve as a stimulus since schizophrenia patients that contribute
      to recovery give mental health professionals the opportunity to question there
      need for a change in their professional roles. Additionally, schizophrenia
      patients that have experienced The Blue Horse Cafe draw attention to certain
      points and these points can serve as a guide, especially for establishing the
      working METHODS of Community Mental Health Centers.

PMID- 29192940
TI  - [The Relationship of Interleukin-18 and Interleukin-6 Levels with Cognitive
      Functions in Bipolar Disorder].
AB  - OBJECTIVE: Impairment in immune functions is proposed as a key factor in the
      cognitive decline in bipolar disorder (BD) however there is scarcity of research
      on the impact of inflammation on cognitive functions. Our aim is to compare IL-18
      and IL-6 levels in BD patients and controls and to study the relationship between
      IL-18 and IL-6 levels and cognitive impairment METHOD: Thirty-six euthymic BD-I
      patients and 38 age, sex and educational level matched healthy controls were
      enrolled in the study. All participants were evaluated with neurocognitive tests.
      The plasma IL-6 and IL-18 levels of both groups were measured with ELISA kits.
      RESULTS: There was no statistically significant difference between IL-6 and IL-18
      levels of patient and healthy control groups. In the patient group, IL-18 level
      was positively correlated with completed categories score wheras there was a
      negative correlation with perseverative response and perseverative errors.
      Moreover IL-18 level was positively correlated with immediate recall, delayed
      recall and learning scores while there was a negative correlation with stroop
      interference scores. No correlation was found between IL-6 level and
      neuropsychological test scores in the patient group. CONCLUSION: This is the
      first study that investigates the relation of IL-18 with cognitive functions.
      Possible detrimental or protective effects of IL-18 in BD is not yet clear,
      however the positive association of IL-18 level and neuropsychological test
      scores might indicate a neuroprotective role of IL-18 in the euthymic period of
      BD which is the closest state to physiological condition.

PMID- 29192941
TI  - [Response With Methylphenidate to ADHD-Like Symptoms in Pervasive Developmental
      Disorder: Does CES-1 Enzyme Gene Polymorphism Have a Role?]
AB  - OBJECTIVE: Methylphenidate is the first-choice medication for the Pervasive
      Developmental Disorders (PDDs), and comorbid Attention Deficit Hyperactivity
      Disorder (ADHD). But this approach generally results with poor outcomes, and
      increased adverse effects. It is aimed to investigate the comparison of cases who
      diagnosed with PDDs and Mild Mental Retardation (MR) and cases with pure ADHD in
      terms of the clinical response to MPH. Also we aimed to investigate the relations
      between CES-1 polymorphism gene and the clinical response to MPH. METHODS: For
      clarifying this we searched for three polymorphisms (Arg199/His, Ser75/Asn, and
      Ile49/Val) in carboxylesterase-1 gene (CES-1) in the saliva of patients diagnosed
      with PDD+ADHD. Also, we assessed the clinical response to MPH by dimensional
      approach using the Attention Deficit Hyperactivity Disorder Rating Scale IV and
      Clinical Global Impression-Improvement scale. RESULTS: PDD+ADHD groups had
      significantly higher Arg199/His polymorphism, and clinically responded poorer
      with symptoms sometimes even worsening to the MPH treatment compared with "pure"
      ADHD and ADHD+MR groups. CONCLUSION: This is the first study that an association
      between Arg199/His polymorphism in CES1 and altered treatment response to MPH in
      patients with PDD that presents with symptoms of ADHD.

PMID- 29192942
TI  - [Adolescent Life Satisfaction Before Young Adulthood: The Role of "Shyness" and
      "Self-Efficacy"].
AB  - OBJECTIVE: The aim of this study was to examine the correlation between shyness,
      perception of general self-efficacy, and life satisfaction in young adolescents.
      METHOD: The study participants included 489 freshman students living in Turkey
      and studying under different faculty at public universities in Ankara (184
      female; 37.6% and 305 male; 62.4%). The subjects ranged in age between 18 (n =
      207; 42.3%) and 19 (n = 282; 57.7%) years. Study data collection included the
      Shyness Scale (Cheek and Buss 1981), the Perception of General Self-efficacy
      Scale (Schwarzer and Jerusalem 1995), and the General Life Satisfaction Scale
      (Diener, Emmons, Laresen and Griffin 1985). The data obtained were examined
      through Correlation analysis, simple linear regression analysis, multiple linear
      regression analysis and the sobel test. RESULTS: The results of the study showed
      that there was a moderately significant negative correlation between shyness and
      perception of general self-efficacy, moderately significant negative correlation
      between shyness and life satisfaction and moderately significant positive
      correlation between the perception of general self-efficacy and life
      satisfaction. Finally, the level of shyness and perceptions of general self
      efficacy significantly predicted life satisfaction. CONCLUSION: The findings of
      the present study may contribute to a better understanding of the relationship
      between shyness, perception of self-efficacy and "life satisfaction. The results
      are discussed in the context of the current literature on these topics.

PMID- 29192943
TI  - [Comparing Two Editions of Wechsler Intelligence Scales and Assessing Reading
      Skills in Children with Attention Deficit and Hyperactivity Disorder].
AB  - OBJECTIVE: This study aimed to examine the cognitive profiles of children with
      Attention Deficit and Hyperactivity Disorder (ADHD) with the Wechsler
      Intelligence Scales for Children-Revised (WISC-R) and the Wechsler Intelligence
      Scales for Children-Fourth Edition (WISC-IV), the latter of which was recently
      standardized in Turkey. In addition, the reading abilities and intelligence
      scores of these children were also investigated. METHODS: A total of 48 children
      with ADHD between the ages of 6 and 16 years who were outpatients in Mus State
      Hospital were included in this study. The children were administered the WISC-R,
      the WISC-IV, and the Oral Reading Skills and Reading Comprehension Test (ORCT).
      RESULTS: There were no significant differences between the WISC-R IQ scores and
      WISC-IV index scores. Moreover, reading comprehension skills (derived from ORCT
      scores) were predicted with significant accuracy by both the WISC-R Verbal IQ and
      the WISC-IV WMI (Working Memory Index). CONCLUSION: Results of this study suggest
      that the WISC-R and the WISC-IV scale are not sufficient for obtaining a specific
      cognitive profile for ADHD - there is no significant difference between them.
      However, the four-factor structure of the WISC-IV is believed to provide more
      specific information. In addition, results of this study related to reading
      skills indicate that the importance of reading skills should not be overlooked
      when assessing children with ADHD.

PMID- 29192945
TI  - [Cognitive Dysfunctions in Posttraumatic Stress Disorder].
AB  - Posttraumatic stress disorder (PTSD) is a condition that occurs after a traumatic
      event, and its diagnostic criteria include attention and memory deficits as well
      as symptoms of anxiety. We aimed to review the literature related to attention,
      memory, and executive functions in PTSD. Although studies on the subject are
      limited (in that there is no uniformity in terms of trauma type, selection of the
      control groups or types of neuropsychological tests used), most reported similar
      deficits in PTSD subjects in terms of memory and executive functions including
      attention. Since the presence of psychiatric comorbidities may disrupt
      neuropsychological functions, results of studies that have not controlled
      comorbidity may be questionable. However, studies that excluded the comorbid
      conditions reported similar deficits in cognitive functions in PTSD patients. The
      relationship between recovery from PTSD symptoms and change in cognitive
      functions has been examined in only a few studies, and most have reported an
      improvement for both memory and executive functions in remitted patients. The
      improvement in executive functions, however, has been limited by the difficulty
      of task. Cognitive deficits have been among the major causes of disabilities in
      PTSD patients. Therefore, the amount of improvement in cognitive dysfunctions by
      current treatments of PTSD deserves more attention.

PMID- 29192944
TI  - [Reliability and Validity Study of the Turkish Version of Hypomania Checklist-32
      Revised].
AB  - OBJECTIVE: In this study, it is aimed to evaluate the reliability and validity of
      the Turkish version of Hypomania Checklist-32-Revised. METHOD: The study was
      carried out with 80 patients diagnosed with bipolar I disorder, 26 patients
      diagnosed with bipolar II disorder and 42 patients diagnosed with major
      depressive disorder attending the out- and in-patient psychiatry departments of
      three university hospitals and one training hospital, and 116 healthy volunteers
      consisting of university students. Mean duration of illness was 15,1 years for
      the bipolar disorder group, and 9,3 years for the major depressive disorder
      group. For concurrent validity, Mood Disorder Questionnaire was used. In the
      statistical analysis, internal consistency coefficient, item-total score
      correlation coefficients, exploratory factor analysis, correlation with
      concurrent scale and ROC curve were calculated. RESULTS: Translation into Turkish
      and back-translation into English of Hypomania Checklist-32-Revised were
      performed and thus the semantic harmony of the scale was obtained. In the
      internal consistency, Cronbach alpha coefficient was 0,914 and item-total score
      correlations were between 0,235-0.743. Solely the coefficient of item #23 was
      found as 0,110. In factor analysis, six factors were obtained but a two-factor
      solution representing 44,5% of the total variance was accepted and first factor
      represents overactivity and being expansive, second factor represents impulsivity
      and risky behaviors. Correlation of Hypomania Checklist-32-R with Mood Disorder
      Questionnaire was r=0,379. In the ROC analysis, the cut off point of the scale
      was calculated as 14 with a sensitivity of 71,0 and specificity of 69,8. The
      scale discriminates well between the bipolar group, and depressive and control
      groups. CONCLUSION: Hypomania Checklist-32-Revised developed for screening
      hypomania is reported to be reliable and valid in Turkish after cutting out item
      #23.

PMID- 29192946
TI  - [Aripiprazole-Induced Hyperhidrosis: Two Case Reports].
AB  - Many drugs including anti-depressants and anti-psychotics are known to cause
      excessive sweating (hyperhidrosis). Hyperhidrosis may be caused by drugs acting
      at the hypothalamus, spinal thermoregulatory centres, and sympathetic ganglia or
      at the eccrine-neuroeffector junction. Hyperhidrosis can be distressing and
      embarrassing symptom, which if not addressed properly, may lead to non
      concordance to medication. Two female patients are reported here who developed
      hyperhidrosis with aripiprazole. Both the patients stopped experiencing
      hyperhidrosis after their aripiprazole was discontinued. To the best of the
      knowledge of the author, no case of aripiprazole induced hyperhidrosis has been
      published in the literature.

PMID- 29192947
TI  - [Executive Functions in Frontal Lob Syndrome: A Case Report].
AB  - Prefrontal cortex in frontal lobe (FL) is the center of executive functions (EF).
      FL damage can lead to executive dysfunction by influencing frontal-subcortical
      circuits (dorsolateral, orbitofrontal, ventromedial). Damage to the dorsolateral
      prefrontal cortex (DLPFC) can lead to deterioration in EF, whereas damage to the
      orbitofrontal cortex (OFC) can lead to personality changes with the
      characteristic of disinhibition and irritability. In addition, damage to the
      anterior cingulate cortex/medial prefrontal cortex (ACC/MPFC) can result in
      decreased spontaneity. Neuropsychological tests are important components in the
      assessment of EF including goal-directed behavior, decision-making, risk
      assessment, making plans for the future, setting of priorities and order of our
      actions. Clinical conditions affecting frontal-subcortical connections outside of
      the FL can also lead to executive dysfunctions and frontal lobe syndrome (FLS).
      This case report is about an adolescent patient diagnosed as FLS. The clinical
      symptoms, assessment and treatment processes of this case are discussed in this
      report. The case is a 15-year-old boy that was admitted to our clinic with
      behavioral problems, which began after a car accident three years ago. Magnetic
      resonance imaging (MRI) of the brain indicated hyperintense signal increase in
      periventricular deep white matter that is associated with traumatic brain damage.
      Neuropsychological tests results (Stroop, Wisconsin Card Sorting Test, Serial
      Digit Learning Test, Line Orientation Test, Verbal Memory Processes Scale) have
      demonstrated impairment in cognitive flexibility, verbal fluency, setting
      priority, inappropriate response inhibition, sustained attention, planning,
      problem solving, organization skills and subcortical memory functions. We thought
      that cognitive and behavioral symptoms of this case were associated with the
      dysfunctions of frontal-subcortical circuits, independent of an obvious frontal
      lesion. FLS for the patients with sudden-onset behavioral and cognitive problems
      after head traumas should be kept in mind in differential diagnosis, even in the
      absence of an obvious frontal lesion.

PMID- 29192948
TI  - [Letter to the Editor: Addiction Psychiatry Fellowship Training In The United
      States].

PMID- 29192949
TI  - [Letter to the Editor: The ICD-11 Chapter On Mental Disorders: An Update For WPA
      Components].

PMID- 29192950
TI  - [Correction: Eyes Test Performance Among Unaffected Mothers of Patients with
      Schizophrenia Turk Psikiyatri Derg 2015; 26 (1): 33-39. DOI: 10.5080/u7460].
AB  - This corrects the article DOI: 10.5080/u7460.

PMID- 29192951
TI  - First-in-man study of dedicated bifurcation cobalt-chromium sirolimus-eluting
      stent BiOSS LIM C(r) - three-month results.
AB  - BACKGROUND: The optimal approach to coronary bifurcation treatment by
      percutaneous coronary intervention (PCI) is still a subject of debate, and
      dedicated bifurcation stents are one of the proposed solutions. AIM: The aim of
      this report was to assess the effectiveness and safety profile of a new dedicated
      bifurcation stent - sirolimus-eluting BiOSS LIM C(r) (Balton, Poland) at the
      first three months of a 12-month registry. METHODS: This is a two-centre
      registry, which enrolled patients with non-ST elevation acute coronary syndrome
      (NSTE-ACS) and stable angina. Provisional T-stenting is the obligatory strategy
      of the treatment. Angiographic control is planned at 12 months. The primary
      endpoint is the cumulative rate of cardiac death, myocardial infarction (MI), and
      target lesion revas-cularisation (TLR) at 12 months. RESULTS: A total of 48
      patients with lesions in coronary bifurcations were enrolled (mean age 67.9 +/-
      8.9 years, 14.6% female). There were 20.8% of patients with NSTE-ACS, 93.8% with
      hypertension, 35.4% with diabetes, 52.1% had previous MI, and 47.9% and 14.6%
      underwent prior PCI and coronary artery bypass grafting, respectively. The device
      success rate was 100%. The side branch was treated with an additional classical
      drug-eluting stent implantation in 18.8% of cases. The periprocedural MI (MI type
      4a) was observed in two (4.2%) cases. At three months there was one (2.1%) case
      of TLR. No death, MI, or stent thrombosis were observed in the follow-up period.
      CONCLUSIONS: Bifurcation treatment with a single dedicated bifurcation stent
      (BiOSS LIM C(r)) is feasible and highly successful (100% implantation success
      rate). The short-term clinical outcomes are very promising, also in distal left
      main stenosis. The 12-month observations are pending.

PMID- 29192952
TI  - Thromboelastography for predicting bleeding in patients with aortic stenosis
      treated with transcatheter aortic valve implantation.
AB  - BACKGROUND: Bleeding complications are frequent and independently impact
      mortality after transcatheter aortic valve implantation (TAVI).
      Thromboelastography (TEG) measures viscoelastic properties of clot formation and
      is currently best known for perioperative management to reduce blood transfusion
      in cardiac surgery. AIM: We sought to determine whether TEG may be predictive of
      bleeding in patients treated with TAVI. METHODS AND RESULTS: Overall, 54
      consecutive patients with severe aortic stenosis treated with TAVI were
      prospectively included. In all patients, two blood samples were obtained for TEG
      measurement (the first - 12 h prior to procedure tested with citrated kaolin [CK]
      TEG assay, and the second - immediately after prosthesis deployment tested with
      CK and citrated heparinised kaolin assay [CHK]). Major or life-threatening
      bleeding (MLTB) was diagnosed in 13 (24%) patients. In receiver-operating
      characteristic (ROC) curve analysis the only TEG parameters showing significant
      sensitivity and specific-ity for predicting MLTB were those obtained in the CK
      sample at the end of the procedure: R value (reaction time, time to initiation of
      clot formation) area under the curve (AUC) 0.69, 95% confidence interval (CI)
      0.49-0.88, p = 0.04; angle (the rate of clot formation), AUC 0.75, 95% CI 0.59
      0.92, p = 0.007, and maximum amplitude (MA, ultimate strength of fibrin clot),
      AUC 0.77, 95% CI 0.62-0.93, p = 0.003. After controlling for confounding factors
      on multivariate logistic regression, MA remained as the only TEG parameter that
      significantly correlated with bleeding after TAVI, both as a continuous variable
      (p = 0.004; 95% CI 0.92-0.98; odds ratio [OR] 0.95 per 1 mm increment) and after
      using the cut-off value derived from ROC analysis; MA < 46.6 mm (OR 10.4; 95% CI
      2.1-51.8; p = 0.004). CONCLUSIONS: Low strength of fibrin clot measured by TEG
      immediately after TAVI may serve as an independent predictor of short-term major
      and life-threatening bleeding complications.

PMID- 29192953
TI  - Relationship between serum homocysteine levels and structural-functional carotid
      arterial abnormalities in inactive Behcet's disease.
AB  - BACKGROUND: Behcet's disease (BD) is a chronic autoimmune disorder with symptoms
      manifesting from an underlying vasculitis. Since the disease activity is
      correlated with characteristic vascular endothelial dysfunction, BD places
      individuals at increased risk of cardiovascular diseases, such as
      atherosclerosis. Hyperhomocysteinaemia is an independent risk factor for
      arteriosclerotic vascular diseases. AIM: This study was designed to investigate
      how plasma homocysteine (Hcy) affects the structural and functional properties of
      the carotid artery in humans. METHODS: Sixty-eight BD patients with subclinical
      atherosclerosis and 40 healthy controls underwent carotid sonography and Doppler
      ultrasound to measure carotid artery intima-media thickness (C-IMT) and carotid
      stiffness and distensibility (indicat-ing elasticity). Total Hcy level was
      determined by enzyme-linked immunosorbent assay. For analysis, the BD patients
      were sub-grouped according to hyperhomocysteinaemia (> 15 MUmol/L). RESULTS: The
      patients with BD were found to have increased C-IMT and beta stiffness and
      decreased distensibility. In addition, hyperhomocysteinaemia was significantly
      correlated with these detrimental changes in the carotid artery, possibly raising
      the risk of these patients developing atherosclerosis. CONCLUSIONS: These
      findings suggest a potential mechanism of atherosclerosis in BD and highlight the
      processes that future research should focus on to address identification and
      prophylactic treatment of BD patients at risk of cardiovascular disease.

PMID- 29192954
TI  - Is heart rate recovery index a predictive factor for cardioinhibitory syncope?
AB  - BACKGROUND: Cardioinhibitory syncope is related with excessive bradycardia or
      asystole due to parasympathetic response. AIM: We investigated whether patients
      with cardioinhibitory syncope have higher heart rate recovery index (HRRi)
      considered as a parasympathetic system activation in exercise stress testing
      (EST) than in those with other neurogenic syncope forms. METHODS: A total of 262
      patients who had neurogenic syncope documented by head-up tilt test (HUTT) and
      199 healthy control individuals were examined. A maximal EST was applied to all
      patients after the HUTT. The HRRi was obtained by subtracting the heart rate that
      was measured at the first (HRRi-1), second (HRRi-2), and third minute (HRRi-3) of
      the recovery period from the maximal heart rate that was measured during the
      test. RESULTS: Eighty patients had cardioinhibitory syncope, 118 patients had
      vasodepressor syncope, and 64 patients had mixed-type syncope. The HRRi-1 was
      higher in patients with syncope (43.3 +/- 7.7) compared to the control group
      (34.5 +/- 4.8; p < 0.001). Post hoc analysis showed that among the syncope
      groups, there was no difference between patients with vasodepressor syncope (42.2
      +/- 7.6) and those with mixed type syncope (40.7 +/- 4.1) in terms of HRRi-1 (p =
      0.420). However, patients with cardioinhibitory syncope (47 +/- 8.7) had a higher
      HRRi-1 than vasodepressor and mixed-type syncope groups (p < 0.05). The threshold
      value of the HRRi-1, which can be used for the prediction of cardioinhibitory
      syncope development, was determined to be 41 with 75% sensitivity and 72%
      specificity. CONCLUSIONS: The HRRi-1 was higher in patients with cardioinhibitory
      syncope compared to the controls. The HRRi-1 has the predictive feature of
      differentiating cardioinhibitory syncope from other syncope types.

PMID- 29192955
TI  - Epidemiology of dyslipidaemia in professional drivers: results of RACER-ABPM
      (Risk of Adverse Cardiovascular Events among professional dRivers in Poland -
      Ambulatory Blood Pressure Monitoring) study.
AB  - BACKGROUND: Professional drivers are a group exposed to many cardiovascular risk
      factors. Non-systematic working hours, prolonged stress, low physical activity,
      along with irregular, and in most cases, unhealthy meals are common aspects of
      the normal working schedule of most of the professional drivers. These translate
      into high risk of cardiovascular disease (CVD). AIM: The aim of the current
      analysis was to establish the prevalence of dyslipidaemia in a group of
      continuous professional drivers. METHODS: The RACER (Risk of Adverse
      Cardiovascular Events among professional dRivers in Poland - Ambulatory Blood
      Pressure Monitoring) study is a prospective study focused on assessing
      cardiovascular risk factors in professional drivers. Patients included in the
      study were screened for classical and non-classical cardiovascular risk factors
      and had an ambulatory blood pressure monitoring (ABPM) performed. Out of the
      whole RACER study population, 144 drivers were included into the RACER-ABPM
      study. RESULTS: Out of this group 135 (95.7%) were male, and the mean age was
      50.2 +/- 9.3 years, and mean body mass index was 32.3 +/- 3.0 kg/m2. A family
      history of CVD was noted in 21.3% of patients, 28.1% were current smokers, and
      2.9% had diabetes mellitus. Out of those patients, 72.2% had low-density
      lipoprotein cholesterol (LDL-C) level > 115 mg/dL, 85.5% had LDL-C > 100 mg/dL,
      and 96.7% had LDL-C > 70 mg/dL. High-density lipoprotein cholesterol < 40 mg/dL
      in men and < 45 mg/dL in women was present in 84.4% of cases. Triglycerides > 150
      mg/dL were found in 28.9% of cases. CONCLUSIONS: In conclusion, dyslipidaemia is
      highly prevalent in professional drivers. Obesity is one of the major
      contributors to the cardiovascular risk, and dyslipidaemia along with other risk
      factors highly prevalent in this subgroup accounts for poorer prognosis.

PMID- 29192956
TI  - Initial clinical experience with the first drug (sacubitril/valsartan) in a new
      class - angiotensin receptor neprilysin inhibitors in patients with heart failure
      with reduced left ventricular ejection fraction in Poland.
AB  - BACKGROUND: Sacubitril/valsartan is the first drug from a new class of
      angiotensin receptor neprilysin inhibitors (ARNIs) recommended in the new
      European Society of Cardiology guidelines instead of angiotensin converting
      enzyme inhibitors (ACEI), or angiotensin receptor blockers (ARB) that are used if
      ACEI are not tolerated. Sacubitril/valsartan is recommended for further reduction
      in the risk of hospitalisation or death in outpatients with heart failure with
      reduced ejection fraction (HFrEF) if symptoms continue despite optimal treatment
      with ACEI/ARB, beta-blockers, and mineralocorticoid antagonists. AIM: The aim of
      this study is to present the initial experience with regard to the effectiveness,
      tolerance, and safety of sacubitril/valsartan in the outpatient cardiology
      practice in Poland. METHODS: The study is a retrospective analysis of data
      obtained through a questionnaire filled in by the physicians who initiated the
      sacubitril/valsartan treatment in patients with HFrEF between 1 June 2016 and 30
      September 2016. Patients were followed-up for three months. RESULTS: The analysis
      included data on 28 patients aged 61 +/- 16 years, of whom 85.7% were males. The
      drug was used in patients in New York Heart Association (NYHA) class I-III. In 25
      (89.2%) patients sacubitril/valsartan was started at the lowest dose (24/26 mg
      BID). During follow-up the sacubitril/valsartan-treated patients had a reduction
      in HF symptoms assessed using the NYHA functional class (p = 0.001), a
      significant drop in N-terminal-pro B-type natriuretic peptide levels (mean, from
      2900 to 2270 pg/mL; p = 0.008), and improved exercise tolerance, which occurred
      shortly after treatment initiation - after a mean of 28 days. CONCLUSIONS: It was
      demonstrated that the use of sacubitril/valsartan in outpatients with HFrEF is
      safe and is associated with a significant clinical improvement.

PMID- 29192957
TI  - The efficacy and safety of valsartan and a combination of valsartan and
      hydrochlorothiazide in the treatment of patients with mild to moderate arterial
      hypertension: a subgroup analysis of the effect of valsartan and its combination
      with....
AB  - BACKGROUND AND AIM: The aim of the study was to establish the effect of valsartan
      and combination of valsartan and hydrochlorothiazide (HCTZ) on pulse wave
      velocity (PWV) and central blood pressure (CBP) in a large population of patients
      with mild to moderate arterial hypertension. METHODS: This was an international,
      multicentre, open-label, prospective trial. After one week of washout in
      previously treated patients, 74 subjects were treated with valsartan or valsartan
      combined with HCTZ for 16 weeks according to the protocol. Naive patients
      received the treatment immediately. During the active treatment, four visits were
      planned for each patient to obtain data for the primary and secondary efficacy.
      At the beginning and at the end of the study PWV and CBP were determined with
      central arterial pressure waveform analysis (SphygmoCor(r), Atcor Medical). This
      study is registered with clinicaltrialsregister.eu, EudraCT number 2012-005129
      57. RESULTS: The results of the present VICTORY trial showed that valsartan and
      combination of valsartan and HCTZ effectively reduced the brachial blood pressure
      in patients with mild to moderate arterial hypertension as well as PWV, central
      systolic blood pressure and central diastolic blood pressure. The effects on the
      augmentation index were not statistically significant. CONCLUSIONS: Valsartan and
      valsartan/HCTZ improve arterial stiffness in patients with mild to moderate
      hypertension.

PMID- 29192958
TI  - Functional implications of novel ADAM10 mutations in reticulate acropigmentation
      of Kitamura.

PMID- 29192959
TI  - Randomized split-face, controlled comparison of treatment with 1565-nm
      nonablative fractional laser for enlarged facial pores.

PMID- 29192960
TI  - Nicotinamide and skin cancer chemoprevention: The jury is still out.
AB  - Following the publication of the results of a Phase III trial, the administration
      of oral nicotinamide has been widely advocated as effective in non-melanoma skin
      cancer chemoprevention in high-risk individuals. However, I performed a Bayesian
      analysis of the reported findings and show there is insufficient evidence to
      demonstrate its efficacy, highlighting the significant probability that the
      positive conclusions drawn will not be reproducible. Given the potential
      widespread use of oral nicotinamide, future position statements regarding its
      efficacy are likely to require higher standards of evidence.

PMID- 29192961
TI  - The incidence and outcome of clinically significant antibodies detected in Rhesus
      D positive pregnant women of the Northern Territory.
AB  - BACKGROUND: Haemolytic disease of the fetus/newborn secondary to clinically
      significant non-Rhesus-D antibodies has risen in importance since the advent of
      immunoprophylactic anti-D administration to Rhesus-D negative women. Of interest
      is the incidence of these antibodies in Rhesus-D positive women, who receive less
      frequent antenatal alloantibody screening. This is of particular concern if the
      antibodies arise late in pregnancy and may go undetected. AIMS: To assess the
      proportion of Rhesus-D positive pregnant women with late developing clinically
      significant antibodies for haemolytic disease of the fetus/newborn, and whether
      these resulted in adverse fetal outcomes. MATERIALS AND METHODS: A retrospective
      analysis over a 12-month period at a tertiary hospital in the Northern Territory.
      Group and antibody screen results in addition to clinical data regarding
      pregnancy/newborn were collected. RESULTS: Sixty-four of 2612 women (2.5%) had
      red blood cell antibodies detected during their pregnancy. Of these, 21
      clinically significant antibodies were detected in 19 women (0.7% of initial
      cohort). The most common antibody detected was anti-c (28.5%). In six of these
      women (0.23% of initial cohort), the antibodies were late developing. Mild
      jaundice was noted in three newborns with phototherapy required in one.
      CONCLUSIONS: Although clinically significant antibodies were detected during
      pregnancy, and in a small proportion of cases as a late developing antibody
      undetected in the first trimester screening, clinical outcomes for the newborn
      were mild. As such, the cost of retesting all Rhesus-D positive pregnant women in
      the third trimester would be considerable and unlikely to result in any
      meaningful clinical benefit.

PMID- 29192962
TI  - External validity in perinatal research.
AB  - Recent studies are beginning to focus on the external validity of well conducted
      internally valid research. This review gives an overview of external validity,
      the dimensions involved and suggestions for when future intervention trials are
      designed, using examples from perinatal research. Finally, we remind the
      perinatal researcher that it is their duty to provide extensive details beyond
      those needed to establish internal validity. The latter would help clinicians to
      determine whether the intervention is applicable to their population.

PMID- 29192963
TI  - Reader reaction on the fast small-sample kernel independence test for microbiome
      community-level association analysis.
AB  - Zhan et al. () presented a kernel RV coefficient (KRV) test to evaluate the
      overall association between host gene expression and microbiome composition, and
      showed its competitive performance compared to existing methods. In this article,
      we clarify the close relation of KRV to the existing generalized RV (GRV)
      coefficient, and show that KRV and GRV have very similar performance. Although
      the KRV test could control the type I error rate well at 1% and 5% levels, we
      show that it could largely underestimate p-values at small significance levels
      leading to significantly inflated type I errors. As a partial remedy, we propose
      an alternative p-value calculation, which is efficient and more accurate than KRV
      p-value at small significance levels. We recommend that small KRV test p-values
      should always be accompanied and verified by the permutation p-value in practice.
      In addition, we analytically show that KRV can be written as a form of
      correlation coefficient, which can dramatically expedite its computation and make
      permutation p-value calculation more efficient.

PMID- 29192964
TI  - Resolving classic pityriasis rubra pilaris, mimicker of erythema gyratum repens.

PMID- 29192965
TI  - Trends in readmission rate by route of hysterectomy - a single-center experience.
AB  - INTRODUCTION: The aim of this study was to assess the 60-day readmission rates
      after hysterectomy according to route of surgery and analyze risk factors for
      postoperative readmission. MATERIAL AND METHODS: This retrospective study
      included all women who underwent hysterectomy due to benign conditions from 2009
      to 2015 at a large academic center in Boston. Readmission rates were compared
      among the following four types of hysterectomies: abdominal, laparoscopic,
      robotic and vaginal. RESULTS: There were 3981 hysterectomy cases over the study
      period (628 abdominal hysterectomy, 2500 laparoscopic hysterectomy, 155 robotic
      hysterectomy and 698 vaginal hysterectomy). Intraoperative complications occurred
      more frequently in women undergoing abdominal hysterectomy (4.8%), followed by
      robotic hysterectomy (3.9%), vaginal hysterectomy (1.9%) and laparoscopic
      hysterectomy (1.6%) (p < 0.0001). Readmission rates were not significantly
      different among the groups; women receiving abdominal hysterectomy had an overall
      readmission rate of 3.5%, compared with 3.2% after robotic hysterectomy, 2.9%
      after vaginal hysterectomy and 1.9% after laparoscopic hysterectomy (p = 0.06).
      When stratifying for relevant variables, women who had an laparoscopic
      hysterectomy had a twofold reduction of readmission compared with abdominal
      hysterectomy (odds ratio 0.52, 95% confidence interval 0.31-0.87; p = 0.01).
      There was no significant difference in readmission when robotic hysterectomy or
      vaginal hysterectomy were compared individually with abdominal hysterectomy.
      Regarding risk factors related to readmission it was observed that perioperative
      complications were the largest driver of readmissions (odds ratio 667, 95%
      confidence interval 158-99; p < 0.0001). CONCLUSION: The laparoscopic approach to
      hysterectomy was associated with fewer hospital readmissions compared with the
      abdominal route; vaginal, robotic and abdominal approaches had a similar risk of
      readmission. Perioperative complications represent the main driver of
      readmissions. After adjusting for perioperative factors such as surgeon type and
      complications, no difference in readmissions between the different routes of
      hysterectomy were found.

PMID- 29192966
TI  - Improving identification of idiopathic intracranial hypertension patients in
      Swedish patient register.
AB  - OBJECTIVE: Idiopathic intracranial hypertension (IIH) is often misdiagnosed. This
      can cause problems if conducting register-based studies. The study purpose was to
      produce algorithms that better identify patients with correct diagnosis of IIH in
      the Swedish National Patient Register (NPR). METHODS: Patients with ICD-10 code
      G93.2 for IIH registered in the NPR (2006-2013, Stockholm County) were included
      and diagnosis validated by medical record reviews. Patients were randomized into
      two groups: one used to produce the algorithm (n = 105) and one for validation (n
      = 102). We tested variables possible to extract from registries and used forward
      stepwise logistic regression which provided a predicted probability of correct
      diagnosis for each patient. RESULTS: We included 207 patients of which 135 had
      confirmed IIH. This gave a positive predictive value of 65.2% (CI: 58.4-71.4).
      The algorithm produced with variables extracted from registries, that is, age,
      number of times with diagnosis code G93.2 recorded (>2 times), and acetazolamide
      treatment, predicted the diagnosis correctly 88.2% (CI: 80.3-93.3) of the time.
      Excluding treatment data from the algorithm did not change the prediction
      notably, 86.3% (CI: 78.1-91.7). CONCLUSION: We produced two algorithms that with
      improved accuracy predict whether an IIH diagnosis in the NPR is correct. This
      can be a useful tool when performing register-based studies.

PMID- 29192967
TI  - Targeting Behavioral Symptoms and Functional Decline in Dementia: A Randomized
      Clinical Trial.
AB  - BACKGROUND/OBJECTIVES: Dementia-related behavioral symptoms and functional
      dependence result in poor quality of life for persons with dementia and their
      caregivers. The goal was to determine whether a home-based activity program
      (Tailored Activity Program; TAP-VA) would reduce behavioral symptoms and
      functional dependence of veterans with dementia and caregiver burden. DESIGN:
      Single-blind (interviewer), parallel, randomized, controlled trial
      (Clinicaltrials.gov: NCT01357564). SETTING: Veteran's homes. PARTICIPANTS:
      Veterans with dementia and their family caregivers (N = 160 dyads). INTERVENTION:
      Dyads in TAP-VA underwent 8 sessions with occupational therapists to customize
      activities to the interests and abilities of the veterans and educate their
      caregivers about dementia and use of customized activity. Caregivers assigned to
      attention control received up to 8 telephone-based dementia education sessions
      with a research team member. MEASUREMENTS: Primary outcomes included number of
      behaviors and frequency of their occurrence multiplied by severity of occurrence;
      secondary outcomes were functional dependence, pain, emotional well-being,
      caregiver burden (time spent caregiving, upset with behaviors) and affect at 4
      (primary endpoint) and 8 months. RESULTS: Of 160 dyads (n = 76 TAP-VA; n = 84
      control), 111 completed 4-month interviews (n = 51 TAP-VA; n = 60 control), and
      103 completed 8-month interviews (n = 50 TAP-VA; n = 53 control). At 4 months,
      compared to controls, the TAP-VA group showed reductions in number (difference in
      mean change from baseline = -0.68, 95% CI = -1.23 to -0.13) and frequency by
      severity (-24.3, 95% CI = -45.6 to -3.1) of behavioral symptoms, number of
      activities needing assistance with (-0.80, 95% CI = -1.41 to -0.20), functional
      dependence level (4.09, 95% CI = 1.06, 7.13), and pain (-1.18, 95% CI = -2.10 to 
      0.26). Caregivers of veterans in TAP-VA reported less behavior-related distress.
      Benefits did not extend to 8 months. CONCLUSION: TAP-VA had positive immediate
      effects and no adverse events. Because TAP-VA reduces behavioral symptoms, slows
      functional dependence, and alleviates pain and caregiver distress, it is a viable
      treatment option for families.

PMID- 29192968
TI  - A regression framework for assessing covariate effects on the reproducibility of
      high-throughput experiments.
AB  - The outcome of high-throughput biological experiments is affected by many
      operational factors in the experimental and data-analytical procedures.
      Understanding how these factors affect the reproducibility of the outcome is
      critical for establishing workflows that produce replicable discoveries. In this
      article, we propose a regression framework, based on a novel cumulative link
      model, to assess the covariate effects of operational factors on the
      reproducibility of findings from high-throughput experiments. In contrast to
      existing graphical approaches, our method allows one to succinctly characterize
      the simultaneous and independent effects of covariates on reproducibility and to
      compare reproducibility while controlling for potential confounding variables. We
      also establish a connection between our model and certain Archimedean copula
      models. This connection not only offers our regression framework an
      interpretation in copula models, but also provides guidance on choosing the
      functional forms of the regression. Furthermore, it also opens a new way to
      interpret and utilize these copulas in the context of reproducibility. Using
      simulations, we show that our method produces calibrated type I error and is more
      powerful in detecting difference in reproducibility than existing measures of
      agreement. We illustrate the usefulness of our method using a ChIP-seq study and
      a microarray study.

PMID- 29192969
TI  - Effects of applying universal fetal growth standards in a Scandinavian multi
      ethnic population.
AB  - INTRODUCTION: The question of whether universal growth charts can be used in
      multi-ethnic settings is of general interest. The Intergrowth-21st fetal growth
      and newborn size standards are suggested to represent optimal fetal growth
      regardless of country origin. Our aim was to examine whether women fulfilling the
      strict Intergrowth-21st inclusion criteria were healthier, showed less ethnic
      differences in fetal growth and newborn size, and less adverse perinatal
      outcomes. MATERIAL AND METHODS: Data were drawn from a population-based multi
      ethnic cohort of 823 presumably healthy pregnant women in Oslo, Norway. We
      assessed differences in fetal and neonatal gestational age specific z-scores and
      compared maternal health parameters, pregnancy and birth complications between
      pregnancies fulfilling and not fulfilling the Intergrowth-21st criteria. RESULTS:
      Only 21% of pregnancies enrolled in our cohort fulfilled the Intergrowth-21st
      criteria. Fetal growth deviated substantially from the new standards, in
      particular for ethnic Europeans. Ethnic differences persisted in pregnancies
      fulfilling the criteria. In South Asian fetuses, estimated fetal weight was -0.60
      SD (95% confidence interval -1.00, -0.20) lower at 24 gestational weeks, and
      birthweight was -0.62 SD (-0.95, -0.29) lower, compared with ethnic Europeans.
      Corresponding numbers for Middle-East/North Africans were -0.13 (-0.62, 0.36) and
      -0.60 (-1.00, -0.20). Maternal health indicators and birth complications were
      similar in women fulfilling and not fulfilling the criteria, but the relation
      depended on ethnic origin. CONCLUSIONS: In an urban multi-ethnic Norwegian
      population, applying an extensive list of criteria to define "healthy"
      pregnancies excludes the majority of women but does not cancel ethnic differences
      in fetal growth.

PMID- 29192971
TI  - Extracellular matrix is an influential force in ageing.

PMID- 29192972
TI  - Image Gallery: Cutaneous signs of acute pancreatitis.

PMID- 29192973
TI  - Neonatal aggressive systemic mastocytosis.

PMID- 29192974
TI  - Dapsone is a potentially useful adjuvant therapy for bullous pemphigoid.

PMID- 29192976
TI  - Image Gallery: Generalized circinate cutaneous lesions simulating circinate
      balanitis.

PMID- 29192975
TI  - Importance of recognition and improved treatment for antimelanoma differentiation
      associated protein 5-associated dermatomyositis.

PMID- 29192977
TI  - Needling warts: are we any further forward?

PMID- 29192979
TI  - Going paperless: a new era for patient-reported outcome measures in dermatology.

PMID- 29192980
TI  - New insights into hidradenitis suppurativa: is lipocalin-2 acting as an
      amplifier?

PMID- 29192981
TI  - Organ transplantation and cutaneous squamous cell carcinoma: progress, pitfalls
      and priorities in immunosuppression-associated keratinocyte carcinoma.

PMID- 29192982
TI  - A promising combination: electrical impedance spectroscopy added at baseline
      visit to short-term sequential digital dermoscopy.

PMID- 29192983
TI  - Image Gallery: Juvenile autoimmune pemphigus presenting with diffuse gingival
      hypertrophy and antibodies against desmocollin 3.

PMID- 29192984
TI  - Are moisturizers effective in the treatment of atopic dermatitis?

PMID- 29192985
TI  - Rituximab and short-course prednisone as the new gold standard for new-onset
      pemphigus vulgaris and pemphigus foliaceus.

PMID- 29192987
TI  - Making sense of measures of clinical signs for atopic dermatitis.

PMID- 29192988
TI  - Vitiligo and lupus: more similarities than meets the eye.

PMID- 29192989
TI  - Staphylococcus aureus in atopic dermatitis: a diverse problem?

PMID- 29192990
TI  - Image Gallery: Pitfalls when measuring protoporphyrin IX during photodynamic
      therapy.

PMID- 29192991
TI  - Doxycycline and the treatment for bullous pemphigoid: what outcomes are most
      important to our patients?

PMID- 29192992
TI  - Risk factors revealed: keratinocyte carcinoma following transplant.

PMID- 29192993
TI  - Participating in trials can inform better clinical practice.

PMID- 29192994
TI  - Image Gallery: Moth-eaten alopecia as the only cutaneous symptom of acquired
      secondary syphilis in a 2-year-old boy.

PMID- 29192995
TI  - Regulatory pathways implicated in male androgenetic alopecia pathogenesis.

PMID- 29192996
TI  - British Association of Dermatologists' guidelines for the management of pemphigus
      vulgaris 2017.

PMID- 29192997
TI  - Washing with water and glycerine improves skin barrier function and quality of
      life in patients with podoconiosis.

PMID- 29192998
TI  - Image Gallery: Intravascular large B-cell lymphoma presenting with generalized
      telangiectasia.

PMID- 29192999
TI  - Dapsone: a forgotten and underestimated treatment option for bullous pemphigoid?

PMID- 29193000
TI  - Role of endothelial dysfunction in pathological cutaneous scarring.

PMID- 29193001
TI  - Real-world effect of biologics on quality of life in psoriasis.

PMID- 29193002
TI  - The minor alleles HCP5 rs3099844 A and PSORS1C1 rs3131003 G are associated with
      allopurinol-induced severe cutaneous adverse reactions in Han Chinese: a
      multicentre retrospective case-control clinical study.

PMID- 29193003
TI  - Optical coherence tomography of basal cell carcinoma: influence of location,
      subtype, observer variability and image quality on diagnostic performance.
AB  - BACKGROUND: We previously described the principal results from an observational,
      prospective, multicentre, clinical trial of the diagnostic value of optical
      coherence tomography (OCT) for basal cell carcinoma (BCC) in a clinical setting.
      In this trial, much additional useful information was gathered that warranted
      further analysis, presented here. OBJECTIVES: To investigate the influence of
      candidate diagnostic criteria, OCT image quality, lesion location, and observer
      confidence and interobserver variability on the diagnostic performance of OCT,
      and to assess its potential use for diagnosis of BCC subtypes. METHODS: A total
      of 234 clinically unclear 'pink lesions' were evaluated in three steps: after
      clinical examination, after adding dermoscopy and after adding OCT. In addition
      to the diagnoses (including lesion subtype), observers recorded which of 15
      diagnostic criteria the OCT image contained, their confidence in the diagnoses,
      the OCT image quality and the anatomical location of the lesion. RESULTS:
      Diagnostic performance of OCT did not depend on the lesion's anatomical location.
      Good OCT image quality was correlated with improved diagnostic performance, but
      diagnostic performance for lesions with mediocre image quality was still better
      than by clinical and dermoscopic examination. The main reason for reduced image
      quality was superficial scales and crusting. Observer confidence in diagnosis was
      correlated with diagnostic performance. Interobserver diagnostic performance was
      consistently higher than clinical examination and dermoscopy across all sites.
      BCC subtype could be determined with moderate accuracy, but further independent
      image markers are required. CONCLUSION: OCT is useful in the diagnosis of BCC.

PMID- 29193004
TI  - The usefulness of mutational data on prognosis of myelodysplastic syndromes:
      alone or incorporated into the IPSS-R?

PMID- 29193005
TI  - From remission to cure: bypass or detour?

PMID- 29193006
TI  - A single-institution retrospective cohort study of first-line R-EPOCH
      chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic
      leukaemia karyotype as an adverse prognostic factor.
AB  - Richter Syndrome, an aggressive lymphoma occurring in patients with chronic
      lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline
      based chemoimmunotherapy regimens designed to treat de novo diffuse large B-cell
      lymphoma achieve modest clinical benefit. R-EPOCH (rituximab, etoposide,
      prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater
      activity against aggressive B-cell histologies but has not been studied in
      Richter Syndrome. We conducted a retrospective cohort study of 46 Richter
      Syndrome patients treated with first-line R-EPOCH at our institution between 1
      January 2006 and 31 May 2014. The median progression-free survival (PFS) was 3.5
      months [95% confidence interval (CI): 2.0-7.6] and median overall survival (OS)
      was 5.9 months (95% CI: 3.2-10.3). Toxicity was high and 30% of patients died
      without progression or response. Patients with a complex CLL karyotype had
      significantly shorter PFS and OS (P = 0.005 and P = 0.002, respectively).
      Multivariable analysis identified complex CLL karyotype as the most significant
      predictor of decreased survival [Hazard ratio (HR) 2.72, 95% CI: 1.14-6.52, P =
      0.025], adjusting for number of prior CLL treatments (P = 0.036). Richter
      Syndrome patients with complex CLL karyotype experience poor survival with R
      EPOCH treatment and novel approaches are needed for these patients. In contrast,
      survival of patients without a complex CLL karyotype was similar to patients with
      de novo diffuse large B-cell lymphoma.

PMID- 29193008
TI  - Comparison of gaze behaviour of trainee and experienced surgeons during
      laparoscopic gastric bypass.
AB  - BACKGROUND: Eye tracking presents a novel tool that could be used to profile
      skill levels in surgery objectively. The primary aim of this study was to
      identify differences in gaze behaviour between expert and junior surgeons
      performing a laparoscopic Roux-en-Y gastric bypass (LRYGB) for obesity. METHODS:
      This prospective observational study used a lightweight eye-tracking apparatus to
      determine the difference in gaze behaviours between expert (more than 75
      procedures) and junior (75 or fewer procedures) surgeons at defined stages of
      LRYGB. Primary endpoints were normalized dwell time and fixation frequency.
      Secondary endpoints were blink rate, maximum pupil size and rate of pupil change.
      RESULTS: A total of 20 procedures (12 junior, 8 expert) were analysed. Compared
      with juniors, experts showed a prolonged dwell time on the screen during angle of
      His dissection (median (range) 91.20 (83.40-94.40) versus 68.95 (59.80-87.60) per
      cent; P = 0.001), formation of the retrogastric tunnel (91.50 (85.80-95.50)
      versus 73.60 (34.60-90.50) per cent; P = 0.001) and gastric pouch formation
      (86.95 (83.60-90.20) versus 67.60 (37.10-80.00) per cent P < 0.001). Juniors had
      a greater blink frequency throughout all recorded segments (P < 0.010) and had a
      larger maximum pupil size during all recorded operative segments (P < 0.010).
      Rate of pupil change was greater in juniors in all analysed segments (P < 0.010).
      CONCLUSION: These results suggest that experts display more focused attention on
      significant stimuli, alongside experiencing a reduced mental workload and having
      increased concentration. This has the potential for future use in validation of
      surgical skill in high-stakes assessment.

PMID- 29193007
TI  - Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL
      SCT 2003/2007 trial.
AB  - Relapse remains the major cause of treatment failure in children with high-risk
      acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem
      cell transplantation (allo-SCT). Prognosis is considered dismal but data on risk
      factors and outcome are lacking from prospective studies. We analysed 242
      children with recurrence of ALL after first allo-SCT enrolled in the Berlin
      Frankfurt-Munster (BFM) ALL-SCT-BFM 2003 and ALL-SCT-BFM international 2007
      studies. Median time from allo-SCT to relapse was 7.7 months; median follow-up
      from relapse after allo-SCT until last follow-up was 3.4 years. The 3-year event
      free survival (EFS) was 15% and overall survival (OS) was 20%. The main cause of
      death was disease progression or relapse (86.5%). The majority of children (48%)
      received salvage therapy without second allo-SCT, 26% of the children underwent a
      second allo-SCT and 25% received palliative treatment only. In multivariate
      analyses, age, site of relapse, time to relapse and type of salvage therapy were
      identified as significant prognostic factors for OS and EFS, whereas factors
      associated with first SCT were not statistically significant. Combined approaches
      incorporating novel immunotherapeutic treatment options and second allo-SCT hold
      promise to improve outcome in children with post allo-SCT relapse.

PMID- 29193009
TI  - Do perioperative antibiotics reduce the risk of surgical-site infections
      following excision of ulcerated skin cancers? A Critically Appraised Topic.
AB  - AIM: To review the efficacy of perioperative antibiotics in reducing the risk of
      surgical-site infections (SSIs) following excision of ulcerated skin cancers.
      SETTING AND DESIGN: Study selection, data extraction and analysis were carried
      out independently by four authors. Only randomized controlled trials (RCTs)
      reported in the English language were included. INCLUDED STUDIES: RCTs in the
      English language in which patients received perioperative topical, intralesional
      or oral antibiotics for dermatological surgery, including Mohs micrographic
      surgery in general practice, dermatology or plastic surgery departments, were
      included. OUTCOME: The proportion of participants developing SSI following
      excision of skin lesions. RESULTS: Thirteen RCTs were identified from our
      literature search of PubMed and Embase, which evaluated SSI following use of
      topical (n = 5), oral (n = 3), intramuscular (n = 2), intravenous (n = 1) and
      intralesional antibiotics (n = 2) in dermatological surgery. Two RCTs
      specifically investigated SSIs in ulcerated skin cancer excisions; one RCT
      investigated the SSI rate following surgical treatment specifically for ulcerated
      skin cancers in individuals randomized to topical antibiotics vs. oral
      cephalexin; and one RCT compared intravenous cefazolin with no antibiotic,
      demonstrating significant reduction in SSI rates for ulcerated tumours (P =
      0.04). CONCLUSIONS: The heterogeneity of the RCTs included in this study makes it
      difficult to make a direct comparison of the outcomes measured. High-quality
      evidence demonstrating a beneficial effect of the use of perioperative
      antibiotics to prevent SSI following excision of ulcerated skin cancers is
      lacking. In the absence of an evidence base, we propose that a well-designed
      multicentre RCT could evaluate the effect of perioperative antibiotics following
      excision of ulcerated tumours, and potentially reduce inappropriate antibiotic
      prescription.

PMID- 29193010
TI  - Early versus late recurrence of intrahepatic cholangiocarcinoma after resection
      with curative intent.
AB  - BACKGROUND: The objective of this study was to investigate the characteristics,
      treatment and prognosis of early versus late recurrence of intrahepatic
      cholangiocarcinoma (ICC) after hepatic resection. METHODS: Patients who underwent
      resection with curative intent for ICC were identified from a multi-institutional
      database. Data on clinicopathological characteristics, initial operative details,
      timing and sites of recurrence, recurrence management and long-term outcomes were
      analysed. RESULTS: A total of 933 patients were included. With a median follow-up
      of 22 months, 685 patients (73.4 per cent) experienced recurrence of ICC; 406 of
      these (59.3 per cent) developed only intrahepatic disease recurrence. The optimal
      cutoff value to differentiate early (540 patients, 78.8 per cent) versus late
      (145, 21.2 per cent) recurrence was defined as 24 months. Patients with early
      recurrence had extrahepatic disease more often (44.1 per cent versus 28.3 per
      cent in those with late recurrence; P < 0.001), whereas late recurrence was more
      often only intrahepatic (71.7 per cent versus 55.9 per cent for early recurrence;
      P < 0.001). From time of recurrence, overall survival was worse among patients
      who had early versus late recurrence (median 10 versus 18 months respectively; P
      = 0.029). In multivariable analysis, tumour characteristics including tumour
      size, number of lesions and satellite lesions were associated with an increased
      risk of early intrahepatic recurrence. In contrast, only the presence of liver
      cirrhosis was independently associated with an increased likelihood of late
      intrahepatic recurrence (hazard ratio 1.99, 95 per cent c.i. 1.11 to 3.56; P =
      0.019). CONCLUSION: Early and late recurrence after curative resection for ICC
      are associated with different risk factors and prognosis. Data on the timing of
      recurrence may inform decisions about the degree of postoperative surveillance,
      as well as help counsel patients with regard to their risk of recurrence.

PMID- 29193011
TI  - The life-saving power of policy: Lessons from Kentucky.

PMID- 29193013
TI  - Lung cancer incidence and the strength of municipal smoke-free ordinances.
AB  - BACKGROUND: Smoke-free laws reduce disease prevalence. The impact of municipal
      smoke-free laws on lung cancer incidence in Kentucky was examined. The authors
      hypothesized that lung cancer incidence rates would be associated with the
      strength of smoke-free laws. METHODS: This was a secondary analysis of 83,727
      Kentucky residents aged >= 50 years who were newly diagnosed with lung cancer
      from 1995 to 2014. In 2014, 33 municipalities had 1 or more smoke-free laws.
      County-level characteristics included adult smoking rate, sex, race/ethnicity,
      income, physician supply, observed radon values, and rurality. RESULTS:
      Individuals living in communities with comprehensive smoke-free laws were 7.9%
      less likely than those living in communities without smoke-free protections to be
      diagnosed with lung cancer. The difference in lung cancer incidence between
      counties with moderate/weak laws and those without laws was not significant.
      CONCLUSIONS: Comprehensive smoke-free laws were associated with fewer new cases
      of lung cancer, whereas weak or moderate smoke-free laws did not confer the same
      benefit. One hundred percent smoke-free laws, covering all workers and the public
      with few or no exceptions, may be key in reducing new cases of lung cancer.
      Cancer 2018;124:374-80. (c) 2017 American Cancer Society.

PMID- 29193014
TI  - Information barriers and social stratification in higher education: evidence from
      a field experiment.
AB  - Our contribution assesses the role of information barriers for patterns of
      participation in Higher Education (HE) and the related social inequalities. For
      this purpose, we developed a large-scale clustered randomised experiment
      involving over 9,000 high school seniors from 62 Italian schools. We designed a
      counseling intervention to correct student misperceptions of the profitability of
      HE, that is, the costs, economic returns and chances of success of investments in
      different tertiary programs. We employed a longitudinal survey to test whether
      treated students' educational trajectories evolved differently relative to a
      control group. We find that, overall, treated students enrolled less often in
      less remunerative fields of study in favour of postsecondary vocational
      programmes. Most importantly, this effect varied substantially by parental social
      class and level of education. The shift towards vocational programmes was mainly
      due to the offspring of low-educated parents; in contrast, children of tertiary
      graduates increased their participation in more rewarding university fields.
      Similarly, the redistribution from weak fields to vocational programmes mainly
      involved the children of the petty bourgeoisie and the working class, while upper
      class students invested in more rewarding university fields. We argue that the
      status-maintenance model proposed by Breen and Goldthorpe can explain these
      socially differentiated treatment effects. Overall, our results challenge the
      claim that student misperceptions contribute to horizontal inequalities in access
      to HE.

PMID- 29193012
TI  - Advances in targeted therapy for acute myeloid leukaemia.
AB  - In the past few years, research in the underlying pathogenic mechanisms of acute
      myeloid leukaemia (AML) has led to remarkable advances in our understanding of
      the disease. Cytogenetic and molecular aberrations are the most important factors
      in determining response to chemotherapy as well as long-term outcome, but beyond
      prognostication are potential therapeutic targets. Our increased understanding of
      the pathogenesis of AML, facilitated by next-generation sequencing, has spurred
      the development of new compounds in the treatment of AML, particularly the
      creation of small molecules that target the disease on a molecular level. Various
      new agents, such as tyrosine kinase inhibitors, immune checkpoint inhibitors,
      monoclonal or bispecific T-cell engager antibodies, metabolic and pro-apoptotic
      agents are currently investigated within clinical trials. The highest response
      rates are often achieved when new molecularly targeted therapies are combined
      with standard chemotherapy. Presented here is an overview of novel therapies
      currently being evaluated in AML.

PMID- 29193015
TI  - The exomic landscape of t(14;18)-negative diffuse follicular lymphoma with 1p36
      deletion.
AB  - Predominantly diffuse t(14;18) negative follicular lymphoma (FL) with 1p36
      deletion shows distinctive clinical, morphological and molecular features that
      distinguish it from classical FL. In order to investigate whether it possesses a
      unique mutation profile, we performed whole exome sequencing of six well
      characterised cases. Our analysis showed that the mutational landscape of this
      subtype is largely distinct from classical FL. It appears to harbour several
      recurrent mutations, affecting STAT6, CREBBP and basal membrane protein genes
      with high frequency. Our data support the view that this FL subtype should be
      considered a separate entity from classical FL.

PMID- 29193016
TI  - Dupilumab with concomitant topical corticosteroid treatment in adults with atopic
      dermatitis with an inadequate response or intolerance to ciclosporin A or when
      this treatment is medically inadvisable: a placebo-controlled, randomized phase
      III clinical trial (LIBERTY AD CAFE).
AB  - BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease that may
      require systemic therapy. Ciclosporin A (CsA) is a widely used, potent
      immunosuppressant but it is not effective in all patients with atopic dermatitis,
      and side-effects limit its use. Dupilumab, a fully human anti-interleukin 4
      receptor-alpha monoclonal antibody, inhibits signaling of IL-4 and IL-13, key
      drivers of Type 2/Th2-mediated inflammation, and is approved in the U.S.A. and
      the European Union for the treatment of inadequately-controlled moderate-to
      severe atopic dermatitis in adults. OBJECTIVES: To evaluate efficacy and safety
      of dupilumab with concomitant topical corticosteroids (TCS) in adults with atopic
      dermatitis with inadequate response to/intolerance of CsA, or for whom CsA
      treatment was medically inadvisable. METHODS: In this 16-week, double-blind,
      randomized, placebo-controlled, phase III trial, patients were randomized 1 : 1 :
      1 to subcutaneous dupilumab 300 mg weekly (qw) or every 2 weeks (q2w) or placebo.
      All received concomitant medium-potency TCS from Week -2 through Week 16; dosage
      could be tapered if lesions cleared, or stopped for adverse reactions to TCS.
      RESULTS: In total, 390 patients were screened, 325 were randomized, and 318
      completed the trial. Treatment groups had similar baseline characteristics.
      Significantly more patients in the dupilumab qw + TCS and q2w + TCS groups
      achieved >= 75% improvement from baseline in the Eczema Area and Severity Index
      at Week 16 vs. the placebo + TCS group (primary end point) (59.1% and 62.6% vs.
      29.6%, respectively; P < 0.001 vs. placebo + TCS, both doses). Other clinical
      outcomes and atopic dermatitis symptoms were significantly improved in the
      dupilumab qw + TCS and q2w + TCS groups, including pruritus, pain, sleep
      disturbance, symptoms of anxiety and depression, and quality of life (QoL).
      Treatment groups had similar overall rates of adverse events (qw + TCS, q2w + TCS
      and placebo + TCS groups: 69.1%, 72.0% and 69.4%, respectively) and serious
      adverse events (1.8%, 1.9% and 1.9%, respectively). Conjunctivitis was more
      frequent with dupilumab + TCS; skin infections were more frequent with placebo +
      TCS. CONCLUSIONS: Dupilumab + TCS significantly improved signs and symptoms of
      atopic dermatitis and QoL in adults with a history of inadequate response
      to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No
      new safety signals were identified.

PMID- 29193017
TI  - Aggressive lymphomas of the elderly: the DEVEC metronomic chemotherapy schedule
      fits the unfit.

PMID- 29193020
TI  - Mosaic pathogenic HRAS variant in a patient with nevus spilus with agminated
      Spitz nevi and parametrial-uterine rhabdomyosarcoma.

PMID- 29193018
TI  - Obesity negatively impacts outcome in elderly female patients with aggressive B
      cell lymphomas treated with R-CHOP: results from prospective trials of the German
      high grade non-Hodgkin's lymphoma trial group.
AB  - To study if obesity is a risk factor in elderly patients (>60 years) with
      aggressive B-cell lymphoma, the outcomes of 576 elderly patients treated with
      rituximab in the RICOVER-60 trial were analysed in a retrospective study with
      regard to body mass index (BMI) and gender. Of the 576 patients, 1% had low body
      weight (BMI < 18.5), 38% were normal weight (18.5 <= BMI < 25), 42% were
      overweight (25 <= BMI < 30) and 19% were obese (BMI >= 30). Event-free (EFS),
      progression-free (PFS) and overall survival (OS) according to BMI showed no
      significant differences for all and for male patients. EFS (P = 0.041), PFS (P =
      0.038) and OS (P = 0.031) were significantly better for female non-obese
      patients. A multivariate analysis adjusted for International Prognostic Index
      risk factors confirmed these results, with the following hazard ratios (HR) for
      obesity (BMI >= 30) for EFS/PFS/OS: all patients - 1.4/1.4/1.4 (not significant);
      male patients - 1.2/1.2/1.0 (not significant) and female patients - 1.7 (P =
      0.032)/1.9 (P = 0.022)/2.0 (P = 0.017). In conclusion, obesity is a risk factor
      that influences treatment outcome in elderly female patients with aggressive B
      cell lymphoma treated with R-CHOP (rituximab + cyclophosphamide, doxorubicin,
      vincristine, prednisolone). The inferior outcomes in obese female patients may be
      due to faster rituximab clearance in obese females.

PMID- 29193019
TI  - Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study:
      lenalidomide versus investigator's choice in relapsed or refractory mantle cell
      lymphoma.
AB  - In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated
      significantly improved median progression-free survival (PFS) compared with
      investigator's choice (IC) in patients with relapsed/refractory MCL. Here we
      present the long-term follow-up data and results of preplanned subgroup
      exploratory analyses from MCL-002 to evaluate the potential impact of demographic
      factors, baseline clinical characteristics and prior therapies on PFS. In MCL
      002, patients with relapsed/refractory MCL were randomized 2:1 to receive
      lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC
      therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The
      intent-to-treat population comprised 254 patients (lenalidomide, n = 170; IC, n =
      84). Subgroup analyses of PFS favoured lenalidomide over IC across most
      characteristics, including risk factors, such as high MCL International
      Prognostic Index score, age >=65 years, high lactate dehydrogenase (LDH), stage
      III/IV disease, high tumour burden, and refractoriness to last prior therapy. By
      multivariate Cox regression analysis, factors associated with significantly
      longer PFS (other than lenalidomide treatment) included normal LDH levels (P <
      0.001), nonbulky disease (P = 0.045), <3 prior antilymphoma treatments (P =
      0.005), and >=6 months since last prior treatment (P = 0.032). Overall,
      lenalidomide improved PFS versus single-agent IC therapy in patients with
      relapsed/refractory MCL, irrespective of many demographic factors, disease
      characteristics and prior treatment history.

PMID- 29193021
TI  - Bendamustine, bortezomib and rituximab produces durable complete remissions in
      patients with previously untreated, low grade lymphoma.
AB  - This Phase II trial evaluated the efficacy of bendamustine, bortezomib and
      rituximab in patients with previously untreated low-grade lymphoma. Eligible
      patients had low grade lymphoma with no previous systemic disease treatment.
      Treatment for all patients was given in 28-day cycles for a maximum of 6 cycles.
      Patients received rituximab 375 mg/m2 intravenously (IV) on days 1, 8 and 15 of
      cycle 1 and day 1 of cycles 2-6; bendamustine 90 mg/m2 IV on days 1 and 2; and
      bortezomib 1.6 mg/m2 IV on days 1, 8 and 15. Patients were permitted to begin
      maintenance treatment with rituximab 6 months after completion of study treatment
      and after 6-month follow-up assessments had been conducted. Fifty-four eligible
      patients were enrolled. The most common grade 3/4 toxicities were leucopenia
      (28%), neutropenia (30%) and lymphopenia (17%). There were no treatment-related
      deaths and 1 unrelated death on study (embolic stroke). The overall response rate
      was 94% for all patients. The median follow-up was 54 months. Kaplan-Meier
      estimates of progression-free survival and overall survival at 36 months were 75%
      and 88%, respectively. The treatment regimen was well tolerated and produced high
      response rates. Further study of this regimen in patients with previously
      untreated lymphoma is warranted.

PMID- 29193022
TI  - Experimental study of delivery of humidified-warm carbon dioxide during open
      abdominal surgery.
AB  - BACKGROUND: The aim of this study was to monitor the effect of humidified-warm
      carbon dioxide (HWCO2 ) delivered into the open abdomen of mice, simulating
      laparotomy. METHODS: Mice were anaesthetized, ventilated and subjected to an
      abdominal incision followed by wound retraction. In the experimental group, a
      diffuser device was used to deliver HWCO2 ; the control group was exposed to
      passive air flow. In each group of mice, surgical damage was produced on one side
      of the peritoneal wall. Vital signs and core temperature were monitored
      throughout the 1-h procedure. The peritoneum was closed and mice were allowed to
      recover for 24 h or 10 days. Tumour cells were delivered into half of the mice in
      each cohort. Tissue was then examined using scanning electron microscopy and
      immunohistochemistry. RESULTS: Passive air flow generated ultrastructural damage
      including mesothelial cell bulging/retraction and loss of microvilli, as assessed
      at 24 h. Evidence of surgical damage was still measurable on day 10. HWCO2
      maintained normothermia, whereas open surgery alone led to hypothermia. The
      degree of tissue damage was significantly reduced by HWCO2 compared with that in
      controls. Peritoneal expression of hypoxia inducible factor 1alpha and vascular
      endothelial growth factor A was lowered by HWCO2 . These effects were also
      evident at the surgical damage sites, where protection from tissue trauma
      extended to 10 days. HWCO2 did not reduce tumorigenesis in surgically damaged
      sites compared with passive air flow. CONCLUSION: HWCO2 diffusion into the
      abdomen in the context of open surgery afforded tissue protection and accelerated
      tissue repair in mice, while preserving normothermia. Surgical relevance Damage
      to the peritoneum always occurs during open abdominal surgery, by exposure to
      desiccating air and by mechanical trauma/damage owing to the surgical
      intervention. Previous experimental studies showed that humidified-warm carbon
      dioxide (HWCO2 ) reduced peritoneal damage during laparoscopic insufflation.
      Additionally, this intervention decreased experimental peritoneal carcinomatosis
      compared with the use of conventional dry-cold carbon dioxide. In the present
      experimental study, the simple delivery of HWCO2 into the open abdomen reduced
      the amount of cellular damage and inflammation, and accelerated tissue repair.
      Sites of surgical intervention serve as ideal locations for cancer cell adhesion
      and subsequent tumour formation, but this was not changed measurably by the
      delivery of HWCO2 .

PMID- 29193023
TI  - Alpha-defensins (alpha-Defs) in Crohn's disease: decrease of ileal alpha-Def 5
      via permanent methylation and increase in plasma alpha-Def 1-3 concentrations
      offering biomarker utility.
AB  - An impaired expression of alpha-defensins (alpha-Defs) in the ileal mucosa and,
      conversely, increased levels in plasma, have been reported in Crohn's disease
      (CD). However, the specificity and correlation of these findings with the degree
      of inflammation are unclear. We aimed to characterize the concentration and
      utility of ileal and plasma alpha-Defs in CD and to analyse a potential
      epigenetic mechanism of alpha-Def expression. Peripheral blood samples and ileal
      biopsies were obtained from patients at disease onset (aCD), from those who
      achieved remission (iCD) and from two control groups (healthy controls and non-CD
      aetiology ileitis patients). Plasma alpha-Defs 1-3 and 4 were detected by enzyme
      linked immunosorbent assay (ELISA); alpha-Def 5 by immunolocalization.
      Methylation analysis of the alpha-Def 5 gene was performed using the MassARRAY
      EpiTYPER system. Plasma alpha-Defs 1-3 concentrations were significantly higher
      in aCD with ileal involvement (L1, L3) versus iCD or the control groups. The
      alpha-Defs 1-3 concentrations were also similar to healthy controls in patients
      with non-CD ileitis. There was a significant positive correlation between plasma
      alpha-Defs 1-3 levels in aCD and the endoscopic index, as well as with C-reactive
      protein (CRP) levels. The immunopositivity scoring showed significantly reduced
      alpha-Def 5 expression in ileal inflamed (aCD) versus non-inflamed mucosa (iCD
      and healthy controls). The alpha-Def 5 gene showed a higher methylation status in
      CD patients than controls, regardless of the inflammation. Plasma alpha-Defs 1-3
      concentrations correlate with the degree of inflammation and appear to be
      specific biomarkers of ileal-CD at diagnosis. Ileal alpha-Def 5 expression is
      down-regulated permanently by methylation.

PMID- 29193024
TI  - Weathering of Oil in a Surficial Aquifer.
AB  - The composition of crude oil in a surficial aquifer was determined in two
      locations at the Bemidji, MN, spill site. The abundances of 71 individual
      hydrocarbons varied within 16 locations sampled. Little depletion of these
      hydrocarbons (relative to the pipeline oil) occurred in the first 10 years after
      the spill, whereas losses of 25% to 85% of the total measured hydrocarbons
      occurred after 30 years. The C6-30 n-alkanes, toluene, and o-xylene were the most
      depleted hydrocarbons. Some hydrocarbons, such as the n-C10-24 cyclohexanes, tri-
      and tetra- methylbenzenes, acyclic isoprenoids, and naphthalenes were the least
      depleted. Benzene was detected at every sampling location 30 years after the
      spill. Degradation of the oil led to increases in the percent organic carbon and
      in the delta 13 C of the oil. Another method of determining hydrocarbon loss was
      by normalizing the total measured hydrocarbon concentrations to that of the most
      conservative analytes. This method indicated that the total measured hydrocarbons
      were depleted by 47% to 77% and loss of the oil mass over 30 years was 18% to
      31%. Differences in hydrocarbon depletion were related to the depth of the oil in
      the aquifer, local topography, amount of recharge reaching the oil, availability
      of electron acceptors, and the presence of less permeable soils above the oil.
      The results from this study indicate that once crude oil has been in the
      subsurface for a number of years there is no longer a "starting oil
      concentration" that can be used to understand processes that affect its fate and
      the transport of hydrocarbons in groundwater.

PMID- 29193025
TI  - "Mouse-MRD" in central nervous system acute lymphoblastic leukaemia: assessing
      bone marrow minimal residual disease using a xenograft model - from bedside to
      the bench and back again.

PMID- 29193027
TI  - Leveraging Humanized Animal Models to Understand Human Drug Disposition:
      Opportunities, Challenges, and Future Directions.
AB  - The utility of animal models in understanding drug disposition and extrapolating
      to human in a direct manner is limited, confounded by differences in enzyme and
      transporter substrate specificity and expression between species. Conversely,
      certain clinical pharmacology or mechanistic studies cannot be conducted for
      ethical and practical reasons. Thus, humanized animal models could be useful to
      bridge the gap between preclinical and clinical pharmacology and gain relevant
      insight into the determinants of drug disposition and drug-drug interaction
      (DDI).

PMID- 29193026
TI  - Respiratory sinus arrhythmia: Modeling longitudinal change from 6 weeks to 2
      years of age among low-income Mexican Americans.
AB  - Parasympathetically-mediated heart rate variability (HRV), commonly indexed via
      respiratory sinus arrhythmia (RSA), is theorized to support the physiological
      regulation of emotion; however, little is known about the trajectory of change in
      resting RSA across early development among high-risk populations for whom emotion
      regulation is crucial. This study characterized resting RSA change from 6 weeks
      to 2 years of age among 312 low-income Mexican American infants. RSA was assessed
      longitudinally at 6, 12, 18, 24, 52, 78, and 104 weeks of age. On average,
      resting RSA increased as infants aged, and this change accelerated over time.
      There was significant variance between infants in resting RSA at 6 weeks of age,
      and in the slope, and acceleration of resting RSA change. Intraclass correlation
      among infants' resting RSA measures was minimal, indicating that resting RSA may
      not be "trait-like" during infancy. Results characterize early RSA development
      among a high-risk sample, which can inform theoretical understanding of the
      development of emotional, and behavioral self-regulation in a high-risk
      population, as well as efforts to promote wellbeing across early childhood.

PMID- 29193028
TI  - Connectivity in a Karst System Using Electrical Resistivity Tomography and
      Network Theory.
AB  - The Ring of Cenotes (RC) is an alignment of numerous cenotes (sinkholes) in a
      semicircular form (with a radius of 100 km) located in northwestern Yucatan,
      Mexico. The formation roughly coincides with a concentric ring that corresponds
      to a buried structure, which has been identified as the product of a meteor
      impact, known as the Chicxulub crater. Secondary permeability generated by the
      fracturing and faulting of the sedimentary sequence in the Chicxulub crater has
      favored the karstification process and therefore the development of underground
      rivers that transport water from the mainland to the sea. This study implements
      the network theory to study the hydrological connectivity between a group of 11
      cenotes within the RC. Eight electrical resistivity tomography transects were
      used as an empirical basis. Each transect was acquired directly in the field
      using the SuperSting R1/IP equipment with a dipole-dipole configuration. An
      adapted version of the reliability algorithm for communication networks was used
      as a theoretical model. We found evidence of the existence of water cavities in
      the study area. We made a network from the data and assigned connection
      probabilities among cenotes as a function of the separation length and the number
      of water cavities, as well as their size.

PMID- 29193029
TI  - Recent progress in understanding and manipulating haemoglobin switching for the
      haemoglobinopathies.
AB  - The major beta-haemoglobinopathies, sickle cell disease and beta-thalassaemia,
      represent the most common monogenic disorders worldwide and a steadily increasing
      global disease burden. Allogeneic haematopoietic stem cell transplantation, the
      only curative therapy, is only applied to a small minority of patients. Common
      clinical management strategies act mainly downstream of the root causes of
      disease. The observation that elevated fetal haemoglobin expression ameliorates
      these disorders has motivated longstanding investigations into the mechanisms of
      haemoglobin switching. Landmark studies over the last decade have led to the
      identification of two potent transcriptional repressors of gamma-globin, BCL11A
      and ZBTB7A. These regulators act with additional trans-acting epigenetic
      repressive complexes, lineage-defining factors and developmental programs to
      silence fetal haemoglobin by working on cis-acting sequences at the globin gene
      loci. Rapidly advancing genetic technology is enabling researchers to probe
      deeply the interplay between the molecular players required for gamma-globin
      (HBG1/HBG2) silencing. Gene therapies may enable permanent cures with autologous
      modified haematopoietic stem cells that generate persistent fetal haemoglobin
      expression. Ultimately rational small molecule pharmacotherapies to reactivate
      HbF could extend benefits widely to patients.

PMID- 29193030
TI  - Ankle muscle tenotomy does not alter ankle flexor muscle recruitment bias during
      locomotor-related repetitive limb movement in late-stage chick embryos.
AB  - In ovo, late-stage chick embryos repetitively step spontaneously, a locomotor
      related behavior also identified as repetitive limb movement (RLM). During RLMs,
      there is a flexor bias in recruitment and drive of leg muscle activity. The
      flexor biased activity occurs as embryos assume an extremely flexed posture in a
      spatially restrictive environment 2-3 days before hatching. We hypothesized that
      muscle afferent feedback under normal mechanical constraint is a significant
      input to the flexor bias observed during RLMs on embryonic day (E) 20. To test
      this hypothesis, muscle afference was altered either by performing a tenotomy of
      ankle muscles or removing the shell wall restricting leg movement at E20. Results
      indicated that neither ankle muscle tenotomy nor unilateral release of limb
      constraint by shell removal altered parameters indicative of flexor bias. We
      conclude that ankle muscle afference is not essential to ankle flexor bias
      characteristic of RLMs under normal postural conditions at E20.

PMID- 29193031
TI  - A novel conditional Aire allele enables cell-specific ablation of the immune
      tolerance regulator Aire.
AB  - Medullary thymic epithelial cell (mTEC)-restricted expression of autoimmune
      regulator (Aire) is essential for establishment of immune tolerance. Recently,
      Aire was also shown to be expressed in cells of hematopietic and reproductive
      lineages. Thus, the generation of Airefl/fl mouse strain enables the
      investigation of the cell-specific function of Aire.

PMID- 29193032
TI  - Diagnostic accuracy of early magnetic resonance imaging to determine motor
      outcomes in infants born preterm: a systematic review and meta-analysis.
AB  - AIM: To examine the diagnostic ability of early magnetic resonance imaging (MRI;
      <36wks postmenstrual age) to detect later adverse motor outcomes or cerebral
      palsy (CP) in infants born preterm. METHOD: Studies of infants born preterm with
      MRI earlier than 36 weeks postmenstrual age and quantitative motor data or a
      diagnosis of CP at or beyond 1 year corrected age were identified. Study details
      were extracted and meta-analyses performed where possible. Quality of included
      studies was evaluated with the QUADAS-2 (a revised tool for the quality
      assessment of diagnostic accuracy studies). RESULTS: Thirty-one articles met the
      inclusion criteria, five of which reported diagnostic accuracy and five reported
      data sufficient for calculation of diagnostic accuracy. Early structural MRI
      global scores detected a later diagnosis of CP with a pooled sensitivity of 100%
      (95% confidence interval [CI] 86-100) and a specificity of 93% (95% CI 59-100).
      Global structural MRI scores determined adverse motor outcomes with a pooled
      sensitivity of 89% (95% CI 44-100) and a specificity of 98% (95% CI 90-100).
      White matter scores determined adverse motor outcomes with a pooled sensitivity
      of 33% (95% CI 20-48) and a specificity of 83% (95% CI 78-88). INTERPRETATION:
      Early structural MRI has reasonable sensitivity and specificity to determine
      adverse motor outcomes and CP in infants born preterm. Greater reporting of
      diagnostic accuracy in studies examining relationships with motor outcomes and CP
      is required to facilitate clinical utility of early MRI. WHAT THIS PAPER ADDS:
      Early magnetic resonance imaging (MRI) has reasonable sensitivity and specificity
      to determine later adverse motor outcomes and cerebral palsy (CP). Detection of
      infants who progressed to CP was stronger than motor outcomes. Global MRI scores
      determined adverse motor outcomes more accurately than white matter scores. Few
      studies report diagnostic accuracy of early MRI findings. Diagnostic accuracy is
      required to draw clinically meaningful conclusions from early MRI studies.

PMID- 29193034
TI  - Hypermanganesemia with dystonia, polycythemia and cirrhosis in 10 patients: Six
      novel SLC30A10 mutations and further phenotype delineation.
AB  - Biallelic mutations in the SLC30A10 gene cause an inborn error of Mn metabolism
      characterized by hypermanganesemia, polycythemia, early-onset dystonia, and liver
      cirrhosis (HMDPC). To date, only 14 families from various ethnic groups have been
      reported. Here, we describe 10 patients from 7 unrelated Egyptian families with
      HMDPC. Markedly elevated blood Mn levels, the characteristic basal ganglia
      hyperintensity on T1-weighted images, and variable degrees of extrapyramidal
      manifestations with or without liver disease were cardinal features in all
      patients. Eight patients presented with striking early diseased onset (<=2
      years). Unexpectedly, early hepatic involvement before the neurological
      regression was noted in 3 patients. Mutational analysis of SLC30A10 gene revealed
      6 novel homozygous mutations (c.77T > C (p.Leu26Pro), c.90C > G (p.Tyr30*),
      c.119A > C (p.Asp40Ala), c.122_124delCCT (p.Ser41del), c.780_782delCAT
      (p.Iso260del) and c.957 + 1G > C). Treatment using 2,3 dimercaptosuccinic acid as
      a manganese chelating agent showed satisfactory results with improvement of
      biochemical markers, hepatic manifestations and relative amelioration of the
      neurological symptoms. Our findings present a large cohort of patients with HMDPC
      from same ethnic group. The majority of our patients showed severe and early
      presentation with clear phenotypic variability among sibship. Moreover, we extend
      the phenotypic and mutational spectrum and emphasize the importance of early
      diagnosis and treatment of this potentially fatal disorder.

PMID- 29193033
TI  - Designing a cancer therapeutic peptide by combining the mitochondrial targeting
      domain of Noxa and ErbB2-targeting moieties.
AB  - Many anticancer drugs target epidermal growth factor receptors to inhibit
      receptor tyrosine kinases and tumor growth. Here, we show that an ErbB2-targeting
      pronecrotic peptide (KWSY:MTD) selectively kills tumor cells expressing ErbB2 in
      vitro. An antibody against ErbB2 inhibits KWSY:MTD-induced cell death. KWSY:MTD
      causes membrane permeability which allows propidium iodide entry into the cytosol
      and the release of HMGB1 into the media, indicative of necrosis. Mitochondrial
      swelling occurs in response to KWSY:MTD. Moreover, in vivo analysis using a mouse
      model shows that KWSY:MTD partially suppressed growth in tumor tissue bearing
      ErbB2-expressing cells, but did not have obvious toxicity in mouse liver or
      kidney tissue. Taken together, KWSY:MTD has potential as an ErbB2-targeting
      anticancer drug.

PMID- 29193035
TI  - An immune-molecular hypothesis supporting infectious aetiopathogenesis of
      Kawasaki disease in children.
AB  - The competitive binding between CpG-ODN (single-stranded DNA from pathogens) and
      HLA-B and HLA-A ligands for the inhibitory Killer Immunoglobulin-like Receptors
      (KIR)3DL1/2 may lead to possible hypo-sensing of pathogens and ineffective
      clearance. We observed an overabundance of HLA ligands for inhibitory KIR with
      three domains in KD subjects.

PMID- 29193038
TI  - Emerging Clinical Importance of Hepatic Organic Cation Transporter 1 (OCT1) in
      Drug Pharmacokinetics, Dynamics, Pharmacogenetic Variability, and Drug
      Interactions.
AB  - Hepatic organic cation transporter 1 (OCT1) can be a determinant of drug
      clearance and distribution, which can impact drug exposure and response. OCT1 was
      shown recently to be the rate-determining step in the clearance of several drugs
      in humans, and thereby a mechanism of pharmacogenetic variability and drug-drug
      interactions (DDIs). OCT1 mediates metformin distribution to the liver (key
      biophase). As OCT1 modulation impacts metformin response, but not
      pharmacokinetics (PK), metformin DDI studies require pharmacodynamic endpoint(s)
      to inform rational metformin dose adjustment.

PMID- 29193036
TI  - CXCL4 is a novel inducer of human Th17 cells and correlates with IL-17 and IL-22
      in psoriatic arthritis.
AB  - CXCL4 regulates multiple facets of the immune response and is highly upregulated
      in various Th17-associated rheumatic diseases. However, whether CXCL4 plays a
      direct role in the induction of IL-17 production by human CD4+ T cells is
      currently unclear. Here, we demonstrated that CXCL4 induced human CD4+ T cells to
      secrete IL-17 that co-expressed IFN-gamma and IL-22, and differentiated naive
      CD4+ T cells to become Th17-cytokine producing cells. In a co-culture system of
      human CD4+ T cells with monocytes or myeloid dendritic cells, CXCL4 induced IL-17
      production upon triggering by superantigen. Moreover, when monocyte-derived
      dendritic cells were differentiated in the presence of CXCL4, they orchestrated
      increased levels of IL-17, IFN-gamma, and proliferation by CD4+ T cells.
      Furthermore, the CXCL4 levels in synovial fluid from psoriatic arthritis patients
      strongly correlated with IL-17 and IL-22 levels. A similar response to CXCL4 of
      enhanced IL-17 production by CD4+ T cells was also observed in patients with
      psoriatic arthritis. Altogether, we demonstrate that CXCL4 boosts pro
      inflammatory cytokine production especially IL-17 by human CD4+ T cells, either
      by acting directly or indirectly via myeloid antigen presenting cells,
      implicating a role for CXCL4 in PsA pathology.

PMID- 29193039
TI  - Comment on "The Amazingly Rapid Birth, Growth and Maturing of Digital Computer
      Modeling in Hydrogeology" by F. J. Molz, 2017, v. 55, no. 2: 281-285.

PMID- 29193037
TI  - Model answers: Rational application of murine models in arthritis research.
AB  - Advances in targeted immune therapeutics have profoundly improved clinical
      outcomes for patients with inflammatory arthropathies particularly rheumatoid
      arthritis. The landscape of disease that is observed and the treatment outcomes
      desired for the future have also progressed. As such there is an increasing move
      away from traditional models of end-stage, chronic disease with recognition of
      the need to consider the earliest phases of pathogenesis as a target for
      treatment leading to resolution and/or cure. In order to continue the discovery
      process and enhance our understanding of disease and treatment, we therefore need
      to continuously revisit the animal models we employ and assess their relevance
      and utility in the light of contemporary therapeutic goals. In this review, we
      highlight the areas where we consider new developments in animal models and their
      application are most required. Thus, we have contextualised the relevant mouse
      models and their use within the current concepts of human inflammatory arthritis
      pathogenesis and highlight areas of need.

PMID- 29193040
TI  - Northern pig-tailed macaques (Macaca leonina) maintain superior CD4+ T-cell
      homeostasis during SIVmac239 infection.
AB  - Gradual depletion of CD4+ T cells is a typical characteristic of pathogenic SIV
      infection. Intriguingly, we find a spontaneous CD4+ T-cell homeostasis in
      northern pig-tailed macaques (Macaca leonina) during SIVmac239 infection.

PMID- 29193041
TI  - Early nurse attrition in New Zealand and associated policy implications.
AB  - AIM: To examine the factors contributing to nurses choosing to exit the nursing
      profession before retirement age. BACKGROUND: Population growth, ageing and
      growing demand for health services mean increased demand for nurses. Better
      retention could help meet this demand, yet little work has been done in New
      Zealand to understand early attrition. METHODS: An online survey of registered
      and enrolled nurses and nurse practitioners who had left nursing was used. This
      study reports analysis of responses from 285 ex-nurses aged under 55. FINDINGS:
      The primary reasons nurses left the profession were as follows: workplace
      concerns; personal challenges; career factors; family reasons; lack of
      confidence; leaving for overseas; unwillingness to complete educational
      requirements; poor work-life balance; and inability to find suitable nursing
      work. Most nurses discussed their intentions to leave with a family member or
      manager and most reported gaining transferrable skills through nursing.
      CONCLUSIONS: Nurses leave for many reasons. Implementing positive practice
      environments and individualized approaches to retaining staff may help reduce
      this attrition. Generational changes in the nature of work and careers mean that
      nurses may continue to leave the profession sooner than anticipated by
      policymakers. IMPLICATIONS FOR POLICY: If the nursing workforce is to be able to
      meet projected need, education, recruitment and retention policies must urgently
      address issues leading to early attrition. In particular, policies improving the
      wider environmental context of nursing practice and ensuring that working
      environments are safe and nurses are well supported must be developed and
      implemented. Equally, national nursing workforce planning must take into account
      that nursing is no longer viewed as a career for life.

PMID- 29193042
TI  - Driving Access to Medicines With a Totality of Evidence Mindset: An Opportunity
      for Clinical Pharmacology.
AB  - Access to Medicine (AtM) initiatives have traditionally focused on enabling
      continuous availability and affordability of medicines for patients in the
      developing world. A more holistic view of AtM across the discovery-development
      regulation-utilization continuum would also include participation in the
      development and timely access to emerging therapies in diverse populations in the
      era of precision therapeutics, built upon foundational clinical pharmacology
      principles, leveraging a Totality of Evidence (ToE) mindset.

PMID- 29193043
TI  - The Role of Negative Affect on Headache-Related Disability Following Traumatic
      Physical Injury.
AB  - OBJECTIVE: Acute postinjury negative affect (NA) may contribute to headache pain
      following physical injury. Early psychiatric-headache comorbidity conveys
      increased vulnerability to chronic headache-related disability and impairment.
      Yet, it is unknown whether NA is involved in the transition to chronic headache
      related-disability after injury. This prospective observational study examined
      the role of acute postinjury NA on subacute and chronic headache-related
      disability above and beyond nonpsychiatric factors. METHODS: Eighty adult
      survivors of single-incident traumatic physical injury were assessed for negative
      affect (NA): a composite of depression and anxiety symptoms, and symptoms of
      posttraumatic stress disorder (PTSS) during the acute 2-week postinjury phase. NA
      was examined as the primary predictor of subacute (6-week) and chronic (3-month)
      headache-related disability; secondary analyses examined whether the individual
      NA components differentially impacted the outcomes. RESULTS: Hierarchical linear
      regression confirmed NA as a unique predictor of subacute (Cohen's f 2  = 0.130;
      P = .005) and chronic headache related-disability (Cohen's f 2  = 0.160; P =
      .004) beyond demographic and injury-related factors (sex, prior headaches, and
      closed head injury). Upon further analysis, PTSS uniquely predicted greater
      subacute (Cohen's f 2  = 0.105; P = .012) and chronic headache-related disability
      (Cohen's f 2  = 0.103; P = .022) above and beyond demographic and injury-related
      factors, depression, and anxiety. Avoidance was a robust predictor of subacute
      headache impairment (explaining 15% of the variance) and hyperarousal was a
      robust predictor of chronic headache impairment (10% of the variance).
      CONCLUSION: Although NA consistently predicted headache-related disability, PTSS
      alone was a unique predictor above and beyond nonpsychiatric factors, depression,
      and anxiety. These results are suggestive that early treatment of acute
      postinjury PTSS may correlate with reductions in disability and negative physical
      health sequelae associated with PTSS and chronic headache.

PMID- 29193044
TI  - Accumulation of rest deficiency precedes sudden death of epileptic Kv1.1 knockout
      mice, a model of sudden unexpected death in epilepsy.
AB  - OBJECTIVE: Chronic sleep deficiency is associated with early mortality. In the
      epileptic population, there is a higher prevalence of sleep disorders, and
      individuals with severe refractory epilepsy are at greater risk of premature
      mortality than the general population. Sudden unexpected death in epilepsy
      affects 1:1000 cases of epilepsy each year. Ketogenic diet (KD) treatment is one
      of the few effective options for refractory seizures. Despite KD reducing
      seizures and increasing longevity in Kv1.1 knockout (KO) mice, they still succumb
      to sudden death. This study aims to determine whether (1) the rest profiles of KO
      and KD-treated KO (KOKD) mice resemble each other as a function of either age or
      proximity to death and (2) the timing of death correlates with acute or chronic
      changes in rest. METHODS: Noninvasive actimetry was used to monitor rest
      throughout the lives of KO and wild-type (WT) littermates administered standard
      diet or KD. RESULTS: As KO mice age, rest is reduced (P < .0001). Rest is
      significantly improved in KDKO mice (P < .0001), resembling WT values at several
      ages. When age is removed as a variable and data are realigned to the day of
      death, the rest profiles of KO and KOKD groups worsen to similar degrees as a
      function of proximity to death. The amount of rest acutely is not sensitive to
      the timing of death, whereas chronic rest deficiency profiles (10-15 days prior
      to death) of both groups were indistinguishable. Chronic accumulation of rest
      deficiency over the final 15 days was associated with 75% of deaths.
      SIGNIFICANCE: Our data suggest that the accumulated rest deficiency is associated
      with sudden death in Kv1.1 KO mice. These data (1) support the proposed clinical
      hypothesis that chronic sleep deficiency may be associated with early mortality
      in epileptic patients and (2) warrant future preclinical and clinical studies on
      sleep monitoring in epileptic patients.

PMID- 29193046
TI  - Measurement invariance of the Belief in a Zero-Sum Game scale across 36
      countries.
AB  - In this paper, we examined the psychometric properties of cross-cultural
      validation and replicability (i.e. measurement invariance) of the Belief in a
      Zero-Sum Game (BZSG) scale, measuring antagonistic belief about interpersonal
      relations over scarce resources. The factorial structure of the BZSG scale was
      investigated in student samples from 36 countries (N = 9907), using separate
      confirmatory factor analyses (CFAs) for each country. The cross-cultural
      validation of the scale was based on multigroup confirmatory factor analyses
      (MGCFA). The results confirmed that the scale had a one-factor structure in all
      countries, in which configural and metric invariance between countries was
      confirmed. As a zero-sum belief about social relations perceived as antagonistic,
      BZSG is an important factor related to, for example, social and international
      relations, attitudes toward immigrants, or well-being. The paper proposes
      different uses of the BZSG scale for cross-cultural studies in different fields
      of psychology: social, political, or economic.

PMID- 29193045
TI  - Waist circumference and risk of breast cancer in Korean women: A nationwide
      cohort study.
AB  - Although postmenopausal breast cancer (BC) risk has been linked to adiposity,
      associations between adiposity and premenopausal BC remain unclear. To address
      this question, we investigated the association of BC risk with measures of
      adiposity, including body mass index (BMI) and waist circumference (WC), in a
      large cohort of Asian women. We used a nationwide cohort of adult Korean women
      selected from the National Health Insurance Corporation database merged with
      national health examination data from 2009 to 2015. A total of 11,227,948 women
      were tracked to retrospectively identify incident cases of BC. Our analysis used
      Cox proportional hazards models to calculate hazard ratios and assess the
      association of BC risk with BMI and/or WC in both pre- and postmenopausal women.
      BMI and WC were robustly associated with increased risk for postmenopausal BC
      (ptrend <0.001 for both BMI and WC) but not with premenopausal BC. Association
      between WC and premenopausal BC was only statistically significant when
      considering BMI (ptrend =0.044). In contrast, postmenopausal BC was negatively
      associated with WC when considering BMI (ptrend =0.011). In premenopausal women,
      WC may predict increased BC risk when considering BMI. However, in postmenopausal
      women, WC is not superior to BMI as an indicator of BC risk.

PMID- 29193047
TI  - Prediction of Groundwater Level in Ardebil Plain Using Support Vector Regression
      and M5 Tree Model.
AB  - The Ardebil plain, which is located in northwest Iran, has been faced with a
      recent and severe decline in groundwater level caused by a decrease of
      precipitation, successive long-term droughts, and overexploitation of groundwater
      for irrigating the farmlands. Predictions of groundwater levels can help planners
      to deal with persistent water deficiencies. In this study, the support vector
      regression (SVR) and M5 decision tree models were used to predict the groundwater
      level in Ardebil plain. The monthly groundwater level data from 24 piezometers
      for a 17-year period (1997 to 2013) were used for training and test of models.
      The model inputs included the groundwater levels of previous months, the volume
      of entering precipitation into every cell, and the discharge of wells. The model
      output was the groundwater level in the current month. In order to evaluate the
      performance of models, the correlation coefficient (R) and the root-mean-square
      error criteria were used. The results indicated that both SVR and M5 decision
      tree models performed well for the prediction of groundwater level in the Ardebil
      plain. However, the results obtained from the M5 decision tree model are more
      straightforward, more easily applied, and simpler to interpret than those from
      the SVR. The highest accuracy was obtained using the SVR model to predict the
      groundwater level from the Ghareh Hasanloo and Khalifeloo piezometers with R =
      0.996 and R = 0.983, respectively.

PMID- 29193048
TI  - Occipital Headache in Chronic Lymphocytic Inflammation With Pontine Perivascular
      Enhancement Responsive to Steroids (CLIPPERS).

PMID- 29193049
TI  - Development and validation of Indian Affective Picture Database.
AB  - Since culturally salient stimuli for emotion recognition are scarce in India, we
      developed and validated a set of 140 coloured pictures of six basic emotions
      along with a neutral expression. The expressions were posed by four expressers,
      two males and two females, with mean age of 25.25 (SD 3.77) years. The
      expressions were captured from five different angles keeping the background
      uniform. These pictures were shown to 350 undergraduates who labelled the emotion
      and rated their intensity. The mean biased hit rate was 93.02 (SD 7.33) and mean
      unbiased hit rate was .519 (SD .015). Within subjects ANOVA revealed significant
      main effect of emotion (F(1, 6) = 7.598, p < .001). The t-test value (23.116, p <
      .001) shows that the given emotion was identified correctly by participants
      beyond chance factors. The mean intensity rating was 5.94 (SD .77). Overall, the
      results reveal that the pictures are a valid set of affective stimuli.

PMID- 29193050
TI  - Antagonistic Relationship Between VEP Potentiation and Gamma Power in Visual Snow
      Syndrome.
AB  - OBJECTIVE: Using a "double-pulse" adaptation paradigm, in which two stimuli are
      presented in quick succession, this study examines the neural mechanisms
      underlying potentiation of the visual evoked potential (VEP) in visual snow
      syndrome. BACKGROUND: Visual snow is a persistent visual disturbance
      characterized by rapid flickering dots throughout the visual field. Like the
      related condition of migraine with aura, visual snow has been hypothesized to
      arise from abnormal neuronal responsiveness, as demonstrated by a lack of typical
      VEP habituation to repeated visual stimulation. Yet the exact neural mechanisms
      underlying this effect remain unclear. Previous "double-pulse" experiments
      suggest that typical VEP habituation reflects disruptive gamma-band (50-70 Hz)
      neural oscillations, possibly driven by inhibitory interneurons. Given that
      migraine has been associated with reduced cortical inhibition, we propose here
      that visual snow may likewise reflect diminished inhibitory activity, resulting
      in decreased gamma power following initial visual stimulation and concomitant
      potentiation of the subsequent VEP response. METHODS: We compared VEP responses
      to double-pulse adaptation in a 22-year-old man with a 2-year history of visual
      snow versus a group of age- and gender-matched controls (N = 5). The patient does
      not have a comorbid diagnosis of episodic migraine or migraine with aura, and
      controls had no personal or family history of migraine. RESULTS: In contrast to
      the pattern of habituation observed in controls, visual snow was associated with
      persistent potentiation of the VEP response. Consistent with our predictions,
      time-frequency analysis revealed reduced gamma-band power following the initial
      stimulus in visual snow relative to controls. CONCLUSIONS: These results support
      an antagonistic interplay between gamma power and rapid neural adaptation,
      shedding new light on the neural mechanisms of VEP potentiation in visual snow.

PMID- 29193052
TI  - Association Between Migraine and Suicidal Behaviors: A Nationwide Study in the
      USA.
AB  - BACKGROUND: Recent studies show migraineurs are at an increased risk of
      developing suicidal behaviors, even after controlling for comorbid depression.
      However, previous research has not examined the impact of psychiatric mood
      disorders on suicidal behaviors in migraineurs within a nationally representative
      sample. OBJECTIVE: A cross-sectional study was used to investigate the
      association between migraine and suicidal behaviors and determine whether
      psychiatric comorbidities modify this association in a nationwide inpatient
      cohort. METHODS: We analyzed the Nationwide Inpatient Sample of hospitalizations
      compiled from USA billing data. Migraine, suicidal behaviors, and psychiatric
      disorders were identified based on the International Classification of Diseases,
      9th Revision, Clinical Modification diagnosis codes from hospitalization
      discharges (2007-2012). Weighted national estimates were used to estimate odds
      ratios (OR) and 95% confidence intervals (CI). RESULTS: 156,172,826
      hospitalizations were included, of which 1.4% had a migraine diagnosis and 1.6%
      had a diagnosis of suicidal behavior. Migraineurs had a 2.07-fold increased odds
      of suicidal behaviors (95%CI: 1.96-2.19) compared with non-migraineurs. We
      repeated analyses after stratifying by depression, anxiety, or posttraumatic
      stress disorder (PTSD). Among hospitalizations with depression, migraine was
      associated with a 20% reduced odds of suicidal behaviors (95%CI: 0.76-0.85).
      Among hospitalizations without depression, migraine was associated with 2.35-fold
      increased odds of suicidal behaviors (95%CI: 2.20-2.51). In stratified analyses,
      we noted that among hospitalizations with anxiety, migraineurs had slightly
      increased odds of suicidal behaviors (OR: 1.07, 95%CI: 1.02-1.13). Among
      hospitalizations without anxiety, migraine was associated with a 2.06-fold
      increased odds of suicidal behaviors (95%CI: 1.94-2.20). Similarly, in analyses
      stratified by PTSD, migraine was not associated with an increased risk of
      suicidal behaviors (OR: 1.00, 95%CI: 0.94-1.07) among those with PTSD. However,
      the odds of suicidal behaviors were increased among hospitalizations without PTSD
      (OR: 1.95, 95%CI: 1.84-2.08). CONCLUSION: Chronic conditions that do not affect
      the current hospitalization may not have been reported. The presence of
      psychiatric diagnoses influences associations of suicidal behaviors with migraine
      in a national inpatient sample. Migraineurs with diagnosed comorbid psychiatric
      disorders may be receiving care that mitigates their risk for suicidal behaviors.

PMID- 29193054
TI  - Indomethacin-Responsive Idiopathic Red Ear Syndrome: Case Report and
      Pathophysiology.

PMID- 29193053
TI  - Oral insulin delivery: existing barriers and current counter-strategies.
AB  - OBJECTIVES: The chronic and progressive nature of diabetes is usually associated
      with micro- and macrovascular complications where failure of pancreatic beta-cell
      function and a general condition of hyperglycaemia is created. One possible
      factor is failure of the patient to comply with and adhere to the prescribed
      insulin due to the inconvenient administration route. This review summarizes the
      rationale for oral insulin administration, existing barriers and some counter
      strategies trialled. KEY FINDINGS: Oral insulin mimics the physiology of
      endogenous insulin secreted by pancreas. Following the intestinal absorption of
      oral insulin, it reaches the liver at high concentration via the portal vein.
      Oral insulin on the other hand has the potential to protect pancreatic beta-cells
      from autoimmune destruction. Structural modification, targeting a particular
      tissue/receptor, and the use of innovative pharmaceutical formulations such as
      nanoparticles represent strategies introduced to improve oral insulin
      bioavailability. They showed promising results in overcoming the hurdles facing
      oral insulin delivery, although delivery is far from ideal. SUMMARY: The use of
      advanced pharmaceutical technologies and further research in particulate carrier
      system delivery predominantly nanoparticle utilization would offer useful tools
      in delivering insulin via the oral route which in turn would potentially improve
      diabetic patient compliance to insulin and the overall management of diabetes.

PMID- 29193051
TI  - Interaction between tobacco smoking and hepatitis B virus infection on the risk
      of liver cancer in a Chinese population.
AB  - Although tobacco smoking has been reported as a risk factor for liver cancer, few
      studies have specifically explored the association among Chinese females and the
      potential interaction between smoking and other risk factors. A population-based
      case-control study was conducted and 2,011 liver cancer cases and 7,933 healthy
      controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data
      were collected, and serum hepatitis B surface antigen (HBsAg) and anti-HCV
      antibody were measured. Unconditional logistic regression was used to examine
      association and potential interaction, while semi-Bayes (SB) method was employed
      to make estimates more conservative. The prevalence of serum HBsAg positivity was
      43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever
      smoking were 1.62 (95% confidence interval [CI]: 1.33-1.96) among male and 0.82
      (95% CI: 0.53-1.26) among female. Age at first cigarette, duration of smoking and
      pack-years of smoking were all significantly associated with liver cancer among
      men. Compared to HBsAg-negative never smokers, the adjusted ORs were 1.25 (95%
      CI: 1.03-1.52) for HBsAg-negative ever smokers, 7.66 (95% CI: 6.05-9.71) for
      HBsAg-positive never smokers, and 15.68 (95% CI: 12.06-20.39) for HBsAg-positive
      ever smokers. These different odds ratios indicated super-additive (RERI: 7.77,
      95% CI: 3.81-11.73) and super-multiplicative interactions (ROR: 1.64, 95% CI:
      1.17-2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most
      associations and interactions detected remained statistically significant after
      SB adjustments. Tobacco smoking and HBV infection positively interact in the
      development of liver cancer.

PMID- 29193055
TI  - Facial shape manifestations of growth faltering in Tanzanian children.
AB  - Variation in the shape of the human face and in stature is determined by complex
      interactions between genetic and environmental influences. One such environmental
      influence is malnourishment, which can result in growth faltering, usually
      diagnosed by means of comparing an individual's stature with a set of age
      appropriate standards. These standards for stature, however, are typically
      ascertained in groups where people are at low risk for growth faltering.
      Moreover, genetic differences among populations with respect to stature are well
      established, further complicating the generalizability of stature-based
      diagnostic tools. In a large sample of children aged 5-19 years, we obtained high
      resolution genomic data, anthropometric measures and 3D facial images from
      individuals within and around the city of Mwanza, Tanzania. With genome-wide
      complex trait analysis, we partitioned genetic and environmental variance for
      growth outcomes and facial shape. We found that children with growth faltering
      have faces that look like those of older and taller children, in a direction
      opposite to the expected allometric trajectory, and in ways predicted by the
      environmental portion of covariance at the community and individual levels. The
      environmental variance for facial shape varied subtly but significantly among
      communities, whereas genetic differences were minimal. These results reveal that
      facial shape preserves information about exposure to undernourishment, with
      important implications for refining assessments of nutritional status in children
      and the developmental-genetics of craniofacial variation alike.

PMID- 29193056
TI  - Identification of a novel fusion gene HMGA2-EGFR in glioblastoma.
AB  - Glioblastoma is one of the most malignant forms of cancer, for which no effective
      targeted therapy has been found. Although The Cancer Genome Atlas has provided a
      list of fusion genes in glioblastoma, their role in progression of glioblastoma
      remains largely unknown. To search for novel fusion genes, we obtained RNA-seq
      data from TGS-01 human glioma-initiating cells, and identified a novel fusion
      gene (HMGA2-EGFR), encoding a protein comprising the N-terminal region of the
      high-mobility group AT-hook protein 2 (HMGA2) fused to the C-terminal region of
      epidermal growth factor receptor (EGFR), which retained the transmembrane and
      kinase domains of the EGFR. This fusion gene product showed transforming
      potential and a high tumor-forming capacity in cell culture and in vivo.
      Mechanistically, HMGA2-EGFR constitutively induced a higher level of
      phosphorylated STAT5B than EGFRvIII, an in-frame exon deletion product of the
      EGFR gene that is commonly found in primary glioblastoma. Forced expression of
      HMGA2-EGFR enhanced orthotopic tumor formation of the U87MG human glioma cell
      line. Furthermore, the EGFR kinase inhibitor erlotinib blocked sphere formation
      of TGS-01 cells in culture and inhibited tumor formation in vivo. These findings
      suggest that, in addition to gene amplification and in-frame exon deletion, EGFR
      signaling can also be activated by gene fusion, suggesting a possible avenue for
      treatment of glioblastoma.

PMID- 29193057
TI  - Prognostic utility of six mutated genes for older patients with acute myeloid
      leukemia.
AB  - Approximately 50% of older patients with acute myeloid leukemia (AML) do not
      obtain chromosomal abnormalities as an effective risk-stratification, and present
      cytogenetically normal AML (CN-AML). To develop a reliable prediction model for
      stratifying the risk of these elderly patients, we conducted a study with a
      discovery and validation design. As a result, we found the top 6 mutated genes in
      the discovery cohort of 26 case by the whole exome sequencing, and verified as
      recurrent mutations in the large cohort of 329 patients by Sanger sequencing. The
      top 6 genes were NPM1, FLT3-ITD, DNMT3A, CEBPA double allele, IDH1 and IDH2
      mutations, and the frequency of each gene in the combining cohort was 36.8%,
      19.8%, 20.1%, 5.8%, 14.9% and 22.5%, respectively. In addition, clinical
      variables such as age, white blood cell counts, genes of IDH1 and DNMT3A
      mutations, European LeukemiaNet genotype (NPM1 mutations and lacking FLT3-ITD or
      CEBPA double allele mutations) and treatment protocols were independent factors
      for predicting the probabilities of overall and event-free survival. The
      prediction nomograms based on these significant factors showed accurate
      discrimination. In conclusion, we developed a reliable prediction model for
      stratifying the risk of elderly patients with CN-AML.

PMID- 29193058
TI  - Posttraumatic growth in a heterogeneous sample of traumatically injured patients
      1 year postinjury.
AB  - OBJECTIVE: Posttraumatic growth (PTG) describes positive change resulting from
      challenging life events. The current study examined factors associated with PTG
      in traumatically injured patients 1 year postinjury. METHOD: Participants (N =
      221) in this prospective cohort study included adults admitted to a Level I
      trauma center. Over half the participants (60%) were male, with a mean age of 47.
      Participants completed baseline measures during hospitalization. PTG was assessed
      at 12-month follow-up. RESULTS: Greater PTG was associated with minority
      race/ethnicity, lower income, automotive collision, and premorbid psychological
      disorder other than depression or posttraumatic stress (PTS). These variables are
      also known to predict PTS in trauma patients. Analysis confirmed that greater PTS
      at follow-up was associated with more growth. CONCLUSION: Participants with the
      most growth also experienced the most distress. This finding demonstrates the
      importance of implementing psychological screening and intervention for trauma
      patients in the acute care setting to reduce PTS and facilitate growth.

PMID- 29193059
TI  - Exercise improves nicotine reward-associated cognitive behaviors and related
      alpha7 nAChR-mediated signal transduction in adolescent rats.
AB  - The adolescent brain is vulnerable to long-lasting cognitive disturbances
      resulting from nicotine exposure. Although exercise has been used as an
      intervention for ameliorating cognitive deficits in various disorders, the effect
      on cognitive changes induced by nicotine exposure and its underlying mechanisms
      remain unclear. The purpose of this study was to investigate the effects of
      exercise on nicotine reward-associated cognitive behaviors in adolescent rats
      subjected to nicotine conditioned place preference paradigm (CPP). Male
      adolescent rats were trained on the Go/NoGo task, then subjected to nicotine CPP,
      and then randomly separated into four groups: sedentary (SED), high- (HE),
      moderate- (ME), and low-intensity (LE) exercise. Rats in exercise groups
      performed treadmill running 30 min daily for 10 days. Results showed that MEs had
      shorter escape latencies in the Morris water maze (MWM) test compared to SEDs.
      Although time spent and distance swam in the target quadrant significantly
      increased in both the MEs and HEs, the number of target quadrant crosses
      increased significantly only in MEs. MEs and HEs showed higher performance
      accuracy on NoGo and lower scores on CPP tasks. Expression of alpha7 nicotinic
      acetylcholine receptors (nAChRs) and downstream signaling molecules increased in
      MEs in prefrontal cortex but not hippocampus, with alpha7 nAChRs expression
      positively associated with NoGo accuracy and MWM probe test performance, but
      negatively correlated with CPP scores. The findings of this study suggest that
      moderate-intensity exercise can improve nicotine induced cognitive behaviors, and
      implicates prefrontal cortical alpha7 nAChR-mediated signal transduction as a
      possible mechanism.

PMID- 29193060
TI  - Using progressive ratio schedules to evaluate tokens as generalized conditioned
      reinforcers.
AB  - The properties of operant reinforcers are dynamic and dependent on a number of
      variables, such as schedule and effort. There has been sparse research on the
      generalized conditioned properties of token reinforcement. We evaluated leisure
      items, edible items, and tokens using a progressive ratio schedule with three
      children with diagnoses of ASD and developmental delays. The highest break points
      occurred during the token reinforcement condition for two out of three
      participants, but response rates tended to be higher with edibles. We then
      evaluated the effects of presession access to edibles on the break points of
      edible items and tokens with two participants. Break points decreased only in the
      edible reinforcement condition, and the participants chose to work for leisure
      items rather than edibles when presession access to edibles was in place. These
      findings suggest that the tokens functioned as generalized conditioned
      reinforcers.

PMID- 29193061
TI  - Modern Day Management of Headache Questions and Answers.

PMID- 29193062
TI  - The question-behaviour effect in intergroup attitudes research: When do attitudes
      towards a minority predict a relevant behaviour?
AB  - We hypothesised that the question-behaviour effect, referred to as the influence
      of questioning about a given behaviour on its subsequent performance, is a
      relevant issue when exploring the external validity of intergroup attitudes. In a
      pair of studies, we have corroborated that merely expressing attitudes towards
      the Jewish minority affects people's relevant behaviour towards this group. In an
      Internet study, participants who first completed verbal attitude measures were
      more likely to donate to a Jewish organisation compared to those who completed
      the measures after making the decision to donate. Moreover, responses to attitude
      measures of various types and donating to the Jewish organisation were correlated
      when attitudes had been expressed in the first step. When attitudes were measured
      after the decision to donate, only the responses to the traditional anti-Semitic
      scale were correlated with this behaviour. In the field study, in which the time
      interval between attitude and behaviour measures was introduced, no question
      behaviour effect was observed. We explain the results with reference to cognitive
      dissonance and attitude accessibility mechanisms and discuss them in a broader
      context of attitude-behaviour research.

PMID- 29193063
TI  - Clinical and Autopsy Characteristics of Fatal Methamphetamine Toxicity in
      Australia.
AB  - Characteristics of death attributed solely to methamphetamine toxicity (MT, n =
      93) by forensic pathologists were examined and compared to cases of multiple drug
      toxicity (MDT, n = 634). The mean age of MT cases was 36.7 years, and 86.0% were
      male. Strenuous activity was reported in 12.9%. The most common witness
      observations were: collapse (60.3%), difficulty in breathing (36.2%), and
      hyperthermia (27.6%). MT cases had higher blood methamphetamine (0.54 vs. 0.11
      mg/L) and amphetamine (0.04 vs. 0.02 mg/L) concentrations and lower likelihoods
      for opioids (12.5% vs. 80.9%), hypnosedatives (27.3 vs. 60.7%), antidepressants
      (14.8 vs. 29.8%), and antipsychotics (9.1 vs. 19.7%). MT cases had significantly
      heavier hearts than MDT cases (423.4 vs. 385.8 g) and were more likely to have
      cardiomegaly (37.1 vs. 20.4%) and replacement fibrosis (25.7 vs. 14.5%). The
      clinical picture was of a sudden cardiac event in a middle-aged man with a high
      methamphetamine concentration. Cardiovascular signs of heavy methamphetamine use
      are frequently seen.

PMID- 29193064
TI  - A Morphometric Outline Analysis of Ancestry and Sex Differences in Cranial Shape.
AB  - Forensic anthropological techniques that utilize nonmetric cranial traits to
      estimate sex and ancestry have historically been criticized for their
      subjectivity and qualitative nature. Nonmetric traits, however, continue to be
      valuable tools in identifying remains in forensic investigations. In this study,
      geometric morphometric analyses of cranial outlines were performed to
      quantitatively assess population and sex variation in modern human cranial shapes
      and to verify group differences in previously reported qualitative traits.
      Elliptical Fourier analysis was conducted on two-dimensional images of the left
      lateral, posterior, and superior cranial views from 198 U.S. Black and White
      crania. Results reveal significant sex and population differences in cranial
      shape that generally coincide with traditional qualitative descriptions. Although
      sex classification was relatively low (70.2%), ancestry classification was higher
      (92.4%), indicating that outline analyses that incorporate multiple nonmetric
      traits into a single statistical analysis may provide a more objective and
      accurate means of ancestry classification.

PMID- 29193065
TI  - Stereological assessment of the blood-air barrier and the surfactant system after
      mesenchymal stem cell pretreatment in a porcine non-heart-beating donor model for
      lung transplantation.
AB  - More frequent utilization of non-heart-beating donor (NHBD) organs for lung
      transplantation has the potential to relieve the shortage of donor organs. In
      particular with respect to uncontrolled NHBD, concerns exist regarding the risk
      of ischaemia/reperfusion (IR) injury-related graft damage or dysfunction. Due to
      their immunomodulating and tissue-remodelling properties, bone-marrow-derived
      mesenchymal stem cells (MSCs) have been suspected of playing a beneficial role
      regarding short- and long-term survival and function of the allograft. Thus, MSC
      administration might represent a promising pretreatment strategy for NHBD organs.
      To study the initial effects of warm ischaemia and MSC application, a large
      animal lung transplantation model was generated, and the structural organ
      composition of the transplanted lungs was analysed stereologically with
      particular respect to the blood-gas barrier and the surfactant system. In this
      study, porcine lungs (n = 5/group) were analysed. Group 1 was the sham-operated
      control group. In pigs of groups 2-4, cardiac arrest was induced, followed by a
      period of 3 h of ventilated ischaemia at room temperature. In groups 3 and 4, 50
      * 106 MSCs were administered intravascularly via the pulmonary artery and
      endobronchially, respectively, during the last 10 min of ischaemia. The left
      lungs were transplanted, followed by a reperfusion period of 4 h. Then, lungs
      were perfusion-fixed and processed for light and electron microscopy. Samples
      were analysed stereologically for IR injury-related structural parameters,
      including volume densities and absolute volumes of parenchyma components,
      alveolar septum components, intra-alveolar oedema, and the intracellular and
      intra-alveolar surfactant pool. Additionally, the volume-weighted mean volume of
      lamellar bodies (lbs) and their profile size distribution were determined. Three
      hours of ventilated warm ischaemia was tolerated without eliciting histological
      or ultrastructural signs of IR injury, as revealed by qualitative and
      quantitative assessment. However, warm ischaemia influenced the surfactant
      system. The volume-weighted mean volume of lbs was reduced significantly (P =
      0.024) in groups subjected to ischaemia (group medians of groups 2-4: 0.180-0.373
      MUm3) compared with the sham control group (median 0.814 MUm3). This was due to a
      lower number of large lb profiles (size classes 5-15). In contrast, the intra
      alveolar surfactant system was not altered significantly. No significant
      differences were encountered comparing ischaemia alone (group 2) or ischaemia
      plus application of MSCs (groups 3 and 4) in this short-term model.

PMID- 29193066
TI  - Broader head, stronger bite: In vivo bite forces in European eel Anguilla
      anguilla.
AB  - This work examined three different phenotypes of the yellow-eel stage of the
      European eel Anguilla anguilla, broad-heads, narrow-heads and eels with an
      intermediate head shape. The aim was to see whether broad-headed A. anguilla,
      which generally consume harder, larger prey, such as crustaceans and fish,
      exerted greater bite force than the narrow-headed variant, which mainly consume
      soft, small prey such as chironomid larvae. It was found that in 99 yellow A.
      anguilla, in vivo bite force of broad-heads are higher compared with narrow-heads
      and intermediates.

PMID- 29193067
TI  - The role of S-nitrosylation of kainate-type of ionotropic glutamate receptor 2 in
      epilepsy induced by kainic acid.
AB  - Epilepsy is a chronic brain disease affecting millions of individuals. Kainate
      receptors, especially kainate-type of ionotropic glutamate receptor 2 (GluK2),
      play an important role in epileptogenesis. Recent data showed that GluK2 could
      undergo post-translational modifications in terms of S-nitrosylation (SNO), and
      affect the signaling pathway of cell death in cerebral ischemia-reperfusion.
      However, it is unclear whether S-nitrosylation of GluK2 (SNO-GluK2) contributes
      to cell death induced by epilepsy. Here, we report that kainic acid-induced SNO
      GluK2 is mediated by GluK2 itself, regulated by neuronal nitric oxide synthase
      (nNOS) and the level of cytoplasmic calcium in vivo and in vitro hippocampus
      neurons. The whole-cell patch clamp recordings showed the influence of SNO-GluK2
      on ion channel characterization of GluK2-Kainate receptors. Moreover,
      immunohistochemistry staining results showed that inhibition of SNO-GluK2 by
      blocking nNOS or GluK2 or by reducing the level of cytoplasmic calcium-protected
      hippocampal neurons from kainic acid-induced injury. Finally, immunoprecipitation
      and western blotting data revealed the involvement of assembly of a GluK2-PSD95
      nNOS signaling complex in epilepsy. Taken together, our results showed that the
      SNO-GluK2 plays an important role in neuronal injury of epileptic rats by forming
      GluK2-PSD95-nNOS signaling module in a cytoplasmic calcium-dependent way,
      suggesting a potential therapeutic target site for epilepsy.

PMID- 29193068
TI  - Advanced glycation end-products increase IL-6 and ICAM-1 expression via RAGE,
      MAPK and NF-kappaB pathways in human gingival fibroblasts.
AB  - BACKGROUND AND OBJECTIVES: Diabetes mellitus (DM) is a risk factor for
      periodontal diseases and may exacerbate the progression of the pathogenesis of
      periodontitis. Advanced glycation end-products (AGEs) cause DM complications
      relative to levels of glycemic control and larger amounts accumulate in the
      periodontal tissues of patients with periodontitis and DM. In the present study,
      we investigated the effects of AGEs on the expression of inflammation-related
      factors in human gingival fibroblasts (HGFs) to elucidate the impact of AGEs on
      DM-associated periodontitis. MATERIAL AND METHODS: HGFs were cultured with or
      without AGEs. Cell viability was examined, and RNA and protein fractions were
      isolated from AGE-treated cells. The expression of interleukin (IL)-6,
      intercellular adhesion molecule-1 (ICAM-1), and the receptor for AGE (RAGE) was
      investigated using reverse transcription-polymerase chain reaction, quantitative
      real-time polymerase chain reaction and enzyme-linked immunosorbent assay, and
      reactive oxygen species activity was measured using a kit with 2',7'
      dichlorofluorescin diacetate. Human monocytic cells (THP-1) labeled with a
      fluorescent reagent were co-cultured with HGFs treated with AGEs and IL-6 siRNA,
      and the adhesive activity of THP-1 cells to HGFs was assessed. The expression of
      IL-6 and ICAM-1 was examined when HGFs were pretreated with recombinant human IL
      6, the siRNAs of RAGE and IL-6, and inhibitors of MAPK and NF-kappaB, and then
      cultured with and without AGEs. The phosphorylation of MAPK and NF-kappaB was
      assessed using western blotting. RESULTS: AGEs increased the mRNA and protein
      expressions of RAGE, IL-6, ICAM-1 and reactive oxygen species activity in HGFs,
      and promoted the adhesion of THP-1 cells to HGFs, but had no effect on cell
      viability until 72 hours. Recombinant human IL-6 increased ICAM-1 expression in
      HGFs, while the siRNAs of RAGE and IL-6 inhibited AGE-induced IL6 and ICAM1 mRNA
      expression, and IL-6 siRNA depressed AGE-induced THP-1 cell adhesion. AGEs
      increased the phosphorylation of p38 and ERK MAPKs, p65 NF-kappaB and
      IkappaBalpha, while inhibitors of p38, ERK MAPKs and NF-kappaB significantly
      decreased AGE-induced IL-6 and ICAM-1 expression. CONCLUSION: AGEs increase IL-6
      and ICAM-1 expression via the RAGE, MAPK and NF-kappaB pathways in HGFs and may
      exacerbate the progression of the pathogenesis of periodontal diseases.

PMID- 29193069
TI  - The Flexitarian FlipTM : Testing the Modalities of Flavor as Sensory Strategies
      to Accomplish the Shift from Meat-Centered to Vegetable-Forward Mixed Dishes.
AB  - : The American diet is lacking in plant-based foods and vegetables, higher in
      protein than necessary, and too centered on meat and poultry. Two major dietary
      shifts recommended by the 2015-2020 U.S. Dietary Guidelines are to increase
      vegetable intake and to increase the variety of protein food sources. One
      suggested strategy for doing this is to partially replace meat and poultry with
      vegetables and plant-based ingredients in mixed dishes. This research tested the
      potential of flavor modalities (taste, aroma, trigeminal, and their combination)
      as strategies to increase the sensory appeal of plant-forward dishes. Consumer
      testing (n = 141) was conducted in a cross-sectional design in a laboratory
      setting on 24 recipe variations. Three factors were tested: cuisine (Latin
      American, Mediterranean, and Asian), meat proportion (high-meat/low-vegetable
      versus low-meat/high-vegetable), and flavor strategy (taste, aroma, trigeminal,
      and a reduced-intensity trimodal combination). Statistical analysis was performed
      in R and XLSTAT-Sensory(r) 2017. Four consumer preference segments were
      uncovered. The low-meat dishes achieved parity or higher in consumer acceptance
      across all recipes and flavor strategies. The taste and trigeminal strategies
      both had higher overall acceptability scores than the aroma strategy, and the
      differences were significant (P < 0.05) in some consumer preference segments. The
      consumers successfully characterized the samples using a Check-All-That-Apply
      task, verifying the flavor strategy design. This research provides insight into
      consumer preferences regarding flavor strategies to partially replace meat with
      vegetables in mixed dishes. The trigeminal and trimodal combination strategies
      were found to be the most promising flavor modalities to use to implement this
      shift. PRACTICAL APPLICATION: There is little knowledge of American consumer
      preferences regarding vegetables in mixed dishes. Mixed dishes are a strategy
      recommended by the U.S. Dietary Guidelines to increase vegetable consumption and
      variety of protein sources. This research explores various flavor and culinary
      strategies with which to carry out the mixed dish meat-vegetable swap and to test
      the potential of the Flexitarian FlipTM (the shift from meat-centric to plant
      centric diets). This research shows that individuals have different preferences
      regarding the type of flavor they prefer in mixed dishes (for example, some
      consumers prefer salty and some prefer spicy), so if the dietitian can recommend
      recipes that cater to that client's food and flavor preferences, the client will
      be more likely to adhere to their diet.

PMID- 29193070
TI  - Development of the human shoulder joint during the embryonic and early fetal
      stages: anatomical considerations for clinical practice.
AB  - Although several studies have been published regarding the morphology and
      anatomical variations of the human shoulder joint, most have dealt with adult
      individuals. Those looking into the development of the joint have been focused on
      specific structures or have observed specimens in advanced gestational stages.
      The goal of this paper is to perform a complete analysis of the embryonic and
      early fetal development of the elements in the shoulder joint, and to clarify
      some contradictory data in the literature. In our study, serial sections of 32
      human embryos (Carnegie stages 16-23) and 26 fetuses (9-13 weeks) were analyzed.
      The chondrogenic anlagen of the humerus and the medial border of the scapula can
      be observed from as early as Carnegie stage 17, whereas that of the rest of the
      scapula appears at stage 18. The osteogenic process begins in week 10 for the
      humeral head and week 11 for the scapula. At stage 19 the interzone becomes
      apparent, which will form the glenohumeral joint. In the next stage the
      glenohumeral joint will begin delaminating and exhibiting a looser central band.
      Denser lateral bands will join the humeral head (caput humeri) and the margins of
      the articular surface of the scapula, thus forming the glenoid labrum, which can
      be fully appreciated by stage 22. In 24-mm embryos (stage 21) we can observe, for
      the first time, the long head of the biceps tendon (which is already inserted in
      the glenoid labrum by week 9), and the intertubercular sulcus, whose depth is
      apparent since week 12. Regarding ligamentous structures, the coracohumeral
      ligament is observed at the end of Carnegie stage 23, whereas the primitive
      glenohumeral ligament already appeared in week 10. The results of this study
      provide a detailed description of the morphogenesis, origin and chronological
      order of appearance of the main intrinsic structures of the human shoulder joint
      during late embryonic and early fetal development. We expect these results to
      help explain several functional aspects of the shoulder joint, and to clarify
      some contradictory data in the literature regarding this complex anatomical and
      biomechanical structure, helping future researchers in their efforts.

PMID- 29193071
TI  - Measuring Ucrit and endurance: equipment choice influences estimates of fish
      swimming performance.
AB  - This study compared the critical swimming speed (Ucrit ) and endurance
      performance of three Australian freshwater fish species in different swim-test
      apparatus. Estimates of Ucrit measured in a large recirculating flume were
      greater for all species compared with estimates from a smaller model of the same
      recirculating flume. Large differences were also observed for estimates of
      endurance swimming performance between these recirculating flumes and a free
      surface swim tunnel. Differences in estimates of performance may be attributable
      to variation in flow conditions within different types of swim chambers.
      Variation in estimates of swimming performance between different types of flumes
      complicates the application of laboratory-based measures to the design of fish
      passage infrastructure.

PMID- 29193072
TI  - Syphilis-Cardiovascular Manifestations of the Great Imitator.
AB  - Rates of syphilis are beginning to once again increase, with the World Health
      Organization estimating that in recent years there were 12 million new cases of
      syphilis each year; in 2002, syphilis was responsible for 0.3% of deaths
      globally. At-risk groups include young males (20-29 years), prisoners, and sex
      workers. Increased rates in young females have elevated the numbers of congenital
      cases. Review of the University of Adelaide Pathology Archive revealed four cases
      with significant pathology, which included cardiac gummas and aortic arch
      aneurysms. These cases demonstrate the cardiovascular characteristics of
      untreated syphilis in the tertiary stage. Cases with such advanced pathology will
      only occur where diagnoses have not been made, and/or standard antibiotic therapy
      has not been implemented in the early stage of disease.

PMID- 29193073
TI  - Carbon and Nitrogen Stable Isotope Analyses of Ephedra Plant and Ephedrine
      Samples and Their Application For Methamphetamine Profiling.
AB  - In this study, stable isotope ratio analysis was used to track the precursor
      information of methamphetamine. The delta13 C and delta15 N values of 30 nature
      ephedra plants, 12 synthetic ephedrine/pseudoephedrine (ephedrine), 14 natural
      ephedrine, and 987 seized methamphetamine samples were measured and compared. Due
      to different weather and earth conditions, the delta13 C and delta15 N values of
      ephedra plants grown in the east and the west of Inner Mongolia showed great
      difference. The delta15 N values of ephedra plants were consistent with related
      ephedrine extracted from them. Moreover, the criteria to infer the synthetic
      origin of ephedrine were set up after the analysis of natural and synthetic
      ephedrine samples. Finally, the precursor origins of 949 seized methamphetamine
      samples synthesized by Emde and Nagai method were tentatively inferred.
      Influenced by different preprecursors, the delta13 C values of seized
      methamphetamine samples that synthesized from P2P also showed great difference,
      and this result is consistent with the reported data.

PMID- 29193074
TI  - Effects of 1alpha,25 Dihydroxyvitamin D3 on Pro-inflammatory Cytokines of
      Palmitic Acid Treated Thp-1 Cells.
AB  - : The level of saturated fatty acids, such as palmitic acid (PA), correlates with
      chronic inflammation in obese and metabolic syndrome patients. However, low level
      of vitamin D3 is observed in those conditions. The aim of this study is to
      investigate effects of 1alpha,25(OH)2 D3 on PA-treated THP-1 cells. Using
      quantitative real-time polymerase chain reaction, we measure mRNA expression of
      pro-inflammatory cytokines: TNF-alpha, Interleukin (IL)-1beta, IL-6, and
      chemokine IL-8 under PA and 1alpha,25(OH)2 D3 influence. PA, at all
      concentrations (25-100 MUM), enhanced LPS stimulatory effect on those mRNA
      expression compared to LPS-treated and -untreated cells. Combination with
      1alpha,25(OH)2 D3 increased cytokine expression at high (10-6 M) and high-normal
      (10-8 M) concentrations compared to PA + LPS and LPS alone, both for 2 and 24 h.
      However, low-normal (10-10 M) and low (10-12 M) levels of 1alpha,25(OH)2 D3 could
      not enhance PA effect, but mRNA expression of pro-inflammatory cytokine was
      higher than LPS-treated cells. Upstream pathway of 1alpha,25(OH)2 D3 , which is
      cholecalciferol, also gave the similar result. Further, inhibition of calcium
      pathway does not play a role in this mechanism. Thus, these findings support pro
      inflammatory effect of PA and vitamin D3 on innate immune response, especially on
      fat-induced inflammation. PRACTICAL APPLICATION: The effect of vitamin D3 on
      chronic inflammation in obesity is uncertain. This study shows an in vitro
      possibility that vitamin D3 could exaggerate inflammation when combined with high
      SFAs. The idea of using vitamin D3 supplement to modulate inflammation in fat
      related inflammation needs further refined experiments before its clinical
      application.

PMID- 29193075
TI  - Introducing 3D Printed Models as Demonstrative Evidence at Criminal Trials.
AB  - This case report presents one of the first reported uses of a 3D printed exhibit
      in an English homicide trial, in which two defendants were accused of beating
      their victim to death. The investigation of this crime included a micro-CT scan
      of the victim's skull, which assisted the pathologist to determine the
      circumstances of the assault, in particular regarding the number of assault
      weapons and perpetrators. The scan showed two distinct injury shapes, suggesting
      the use of either two weapons or a single weapon with geometrically distinct
      surfaces. It subsequently served as the basis for a 3D print, which was shown in
      court in one of the first examples that 3D printed physical models have been
      introduced as evidence in a criminal trial in the United Kingdom. This paper
      presents the decision-making process of whether to use 3D printed evidence or
      not.

PMID- 29193076
TI  - Resurgent sodium current promotes action potential firing in the avian auditory
      brainstem.
AB  - KEY POINTS: Auditory brainstem neurons of all vertebrates fire phase-locked
      action potentials (APs) at high rates with remarkable fidelity, a process
      controlled by specialized anatomical and biophysical properties. This is
      especially true in the avian nucleus magnocellularis (NM) - the analogue of the
      mammalian anteroventral cochlear nucleus. In addition to high voltage-activated
      potassium (KHVA ) channels, we report, using whole cell physiology and modelling,
      that resurgent sodium current (INaR ) of sodium channels (NaV ) is equally
      important and operates synergistically with KHVA channels to enable rapid AP
      firing in NM. Anatomically, we detected strong NaV 1.6 expression near hearing
      maturation, which was less distinct during hearing development despite functional
      evidence of INaR , suggesting that multiple NaV channel subtypes may contribute
      to INaR . We conclude that INaR plays an important role in regulating rapid AP
      firing for NM neurons, a property that may be evolutionarily conserved for
      functions related to similar avian and mammalian hearing. ABSTRACT: Auditory
      brainstem neurons are functionally primed to fire action potentials (APs) at
      markedly high rates in order to rapidly encode the acoustic information of sound.
      This specialization is critical for survival and the comprehension of
      behaviourally relevant communication functions, including sound localization and
      distinguishing speech from noise. Here, we investigated underlying ion channel
      mechanisms essential for high-rate AP firing in neurons of the chicken nucleus
      magnocellularis (NM) - the avian analogue of bushy cells of the mammalian
      anteroventral cochlear nucleus. In addition to the established function of high
      voltage-activated potassium channels, we found that resurgent sodium current
      (INaR ) plays a role in regulating rapid firing activity of late-developing
      (embryonic (E) days 19-21) NM neurons. INaR of late-developing NM neurons showed
      similar properties to mammalian neurons in that its unique mechanism of an 'open
      channel block state' facilitated the recovery and increased the availability of
      sodium (NaV ) channels after depolarization. Using a computational model of NM
      neurons, we demonstrated that removal of INaR reduced high-rate AP firing. We
      found weak INaR during a prehearing period (E11-12), which transformed to
      resemble late-developing INaR properties around hearing onset (E14-16).
      Anatomically, we detected strong NaV 1.6 expression near maturation, which became
      increasingly less distinct at hearing onset and prehearing periods, suggesting
      that multiple NaV channel subtypes may contribute to INaR during development. We
      conclude that INaR plays an important role in regulating rapid AP firing for NM
      neurons, a property that may be evolutionarily conserved for functions related to
      similar avian and mammalian hearing.

PMID- 29193077
TI  - Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test
      overdiscriminating?
AB  - OBJECTIVES: The aim of the study was to assess the impact of the differences in
      dissolution profiles of meloxicam tablets on the in-vivo bioavailability
      parameters after oral administration. METHODS: Compare in-vitro dissolution
      testing in the recommended media to evaluate in-vivo bioequivalence outcomes for
      the Biopharmaceutics Classification System Class II weak acidic drugs. Nine
      Beagle dogs received a single oral administration of each formulation (7.5 mg) in
      a three-way crossover design. KEY FINDINGS: The dissolution of meloxicam from
      both test products showed marked differences with that from the reference tablet
      in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow
      or fast dissolution were then compared with the reference product for in-vivo
      bioequivalence study. Both products were bioequivalent with the reference tablet
      in either extent or rate of oral absorption. It indicated that the dissolution
      profiles which discriminated between the formulations in vitro did not accurately
      predict the in-vivo bioequivalence outcomes. CONCLUSIONS: Comparative dissolution
      profiles using similarity factor (f2 ) in the recommended media should be relaxed
      to fulfil the requirements for the development, scale-up and postapproval changes
      to immediate release oral solid dosage forms of meloxicam.

PMID- 29193079
TI  - Statistical Modeling of the Case Information From the Ohio Attorney General's
      Sexual Assault Kit Testing Initiative.
AB  - The Ohio Attorney General's Sexual Assault Kit (SAK) Testing Initiative has
      resulted in nearly 14,000 kits being processed since the initiation of the
      project in 2012. A logistic regression model was fit to the data from 2500 SAKs
      in order to determine the probability of obtaining at least one Combined DNA
      Index System (CODIS) eligible DNA profile based on a number of predictor
      variables. The probability of obtaining at least one CODIS eligible DNA profile
      from an SAK varied as a function of (i) days to kit collection following a sexual
      assault; (ii) years to kit submission to the laboratory for testing following kit
      collection; (iii) the age of the victim; and (iv) the occurrence of victim
      reported consensual sex around the time of the assault and/or kit collection.
      These findings demonstrate the utility of the statistical modeling of data
      obtained from the "forklift" testing approach of sexual assault kits.

PMID- 29193078
TI  - Termination of re-entrant atrial tachycardia via optogenetic stimulation with
      optimized spatial targeting: insights from computational models.
AB  - KEY POINTS: Optogenetics has emerged as a potential alternative to electrotherapy
      for treating heart rhythm disorders, but its applicability for terminating atrial
      arrhythmias remains largely unexplored. We used computational models
      reconstructed from clinical MRI scans of fibrotic patient atria to explore the
      feasibility of optogenetic termination of atrial tachycardia (AT), comparing two
      different illumination strategies: distributed vs. targeted. We show that
      targeted optogenetic stimulation based on automated, non-invasive flow-network
      analysis of patient-specific re-entry morphology may be a reliable approach for
      identifying the optimal illumination target in each individual (i.e. the critical
      AT isthmus). The above-described approach yields very high success rates (up to
      100%) and requires dramatically less input power than distributed illumination We
      conclude that simulations in patient-specific models show that targeted light
      pulses lasting longer than the AT cycle length can efficiently and reliably
      terminate AT if the human atria can be successfully light-sensitized via gene
      delivery of ChR2. ABSTRACT: Optogenetics has emerged as a potential alternative
      to electrotherapy for treating arrhythmia, but feasibility studies have been
      limited to ventricular defibrillation via epicardial light application. Here, we
      assess the efficacy of optogenetic atrial tachycardia (AT) termination in human
      hearts using a strategy that targets for illumination specific regions identified
      in an automated manner. In three patient-specific models reconstructed from late
      gadolinium-enhanced MRI scans, we simulated channelrhodopsin-2 (ChR2) expression
      via gene delivery. In all three models, we attempted to terminate re-entrant AT
      (induced via rapid pacing) via optogenetic stimulation. We compared two
      strategies: (1) distributed illumination of the endocardium by multi-optrode
      grids (number of optrodes, Nopt  = 64, 128, 256) and (2) targeted illumination of
      the critical isthmus, which was identified via analysis of simulated activation
      patterns using an algorithm based on flow networks. The illuminated area and
      input power were smaller for the targeted approach (19-57.8 mm2 ; 0.6-1.8 W)
      compared to the sparsest distributed arrays (Nopt  = 64; 124.9 +/- 6.3 mm2 ; 3.9
      +/- 0.2 W). AT termination rates for distributed illumination were low, ranging
      from <5% for short pulses (1/10 ms long) to ~20% for longer stimuli (100/1000
      ms). When we attempted to terminate the same AT episodes with targeted
      illumination, outcomes were similar for short pulses (1/10 ms long: 0% success)
      but improved for longer stimuli (100 ms: 54% success; 1000 ms: 90% success). We
      conclude that simulations in patient-specific models show that light pulses
      lasting longer than the AT cycle length can efficiently and reliably terminate AT
      in atria light-sensitized via gene delivery. We show that targeted optogenetic
      stimulation based on analysis of AT morphology may be a reliable approach for
      defibrillation and requires less power than distributed illumination.

PMID- 29193080
TI  - The non-peptidic delta-opioid receptor agonist Tan-67 mediates neuroprotection
      post-ischemically and is associated with altered amyloid precursor protein
      expression, maturation and processing in mice.
AB  - Tan-67 is a selective non-peptidic delta-opioid receptor (DOR) agonist that
      confers neuroprotection against cerebral ischemia/reperfusion (I/R)-caused
      neuronal injury in pre-treated animals. In this study, we examined whether post
      ischemic administration of Tan-67 in stroke mice is also neuroprotective and
      whether the treatment affects expression, maturation and processing of the
      amyloid precursor protein (APP). A focal cerebral I/R model in mice was induced
      by middle cerebral artery occlusion for 1 h and Tan-67 (1.5, 3 or 4.5 mg/kg) was
      administered via the tail vein at 1 h after reperfusion. Alternatively,
      naltrindole, a selective DOR antagonist (5 mg/kg), was administered 1 h before
      Tan-67 treatment. Our results showed that post-ischemic administration of Tan-67
      (3 mg/kg or 4.5 mg/kg) was neuroprotective as shown by decreased infarct volume
      and neuronal loss following I/R. Importantly, Tan-67 improved animal survival and
      neurobehavioral outcomes. Conversely, naltrindole abolished Tan-67
      neuroprotection in infarct volume. Tan-67 treatment also increased APP
      expression, maturation and processing in the ipsilateral penumbral area at 6 h
      but decreased APP expression and maturation in the same brain area at 24 h after
      I/R. Tan-67-induced increase in APP expression was also seen in the ischemic
      cortex at 24 h following I/R. Moreover, Tan-67 attenuated BACE-1 expression, beta
      secretase activity and the BACE cleavage of APP in the ischemic cortex at 24 h
      after I/R, which was abolished by naltrindole. Our data suggest that Tan-67 is a
      promising DOR-dependent therapeutic agent for treating I/R-caused disorder and
      that Tan-67-mediated neuroprotection may be mediated via modulating APP
      expression, maturation and processing, despite an uncertain causative
      relationship between the altered APP and the outcomes observed.

PMID- 29193081
TI  - Post-operative surveillance in retroperitoneal soft tissue sarcoma: The
      importance of tumor histology in guiding strategy.
AB  - Crafting effective surveillance strategies for retroperitoneal soft tissue
      sarcomas is difficult given the scarcity of literature on this rare disease. In
      this article, we will summarize the most recent literature on natural history and
      recurrence patterns of RPS compiled from multi-institutional collaborative
      studies and centers with extended follow-up data, and based on this evidence,
      propose principles for histology-based post-operative surveillance protocols.

PMID- 29193082
TI  - A preliminary investigation of the effect of sample collection technique on the
      cell and RNA content of fine-needle aspirates of five canine tumours.
AB  - OBJECTIVES: To evaluate the effect of syringe size, needle size, number of needle
      passes and operator experience on cell yield from tumour fine-needle aspirates,
      and the quantity and quality of extractable RNA. MATERIALS AND METHODS: Fine
      needle aspirates were collected from canine lymphoma, cutaneous mast cell tumour,
      anal gland adenocarcinoma, fibrosarcoma and oral malignant melanoma using nine
      different techniques. RESULTS: There was a significant difference in cell yield
      between fine-needle aspirate techniques for melanoma, lymphoma and anal gland
      adenocarcinoma. The application of suction yielded the largest number of cells.
      Cell numbers in lymphoma and fibrosarcoma aspirates collected by different
      veterinary surgeons were not significantly different. Use of a smaller gauge
      needle and suction increased the quantity of RNA isolated from fibrosarcoma and
      anal gland adenocarcinoma aspirates, but did not influence RNA integrity.
      CLINICAL SIGNIFICANCE: Suction during fine-needle aspiration increases cell
      numbers obtained from five common canine tumours. Suction increases the quantity
      of RNA isolated from anal gland adenocarcinoma and fibrosarcoma aspirates without
      affecting RNA quality. Junior veterinary surgeons gain comparable cell numbers to
      senior staff.

PMID- 29193084
TI  - Gap junctional communication between beta- and delta-cells: another player for
      suppression of glucagon release.

PMID- 29193083
TI  - Integrating expression-related SNPs into genome-wide gene- and pathway-based
      analyses identified novel lung cancer susceptibility genes.
AB  - Traditional pathway analysis map single nucleotide polymorphisms (SNPs) to genes
      according to physical position, which lacks sufficient biological bases. Here, we
      incorporated genetics of gene expression into gene- and pathway-based analysis to
      identify genes and pathways associated with lung cancer risk. We identified
      expression-related SNPs (eSNPs) in lung tissues and integrated these eSNPs into
      three lung cancer genome-wide association studies (GWASs), including 12,843 lung
      cancer cases and 12,639 controls. We used SKAT-C for gene-based analysis, and
      conditional analysis to identify independent eSNPs of each gene. ARTP algorithm
      was used for pathway analysis. A total of 374,382 eSNPs in the GWAS datasets
      survived quality control, which were mapped to 5,084 genes and 2,752 pathways. In
      the gene-based analysis, nine genes showed significant associations with lung
      cancer risk. Among them, TP63 (3q28), RP11-650L12.2 (15q25.1) and CHRNA5
      (15q25.1) were located in known lung cancer susceptibility loci. We also
      validated two newly identified susceptibility loci (RNASET2 and AL133458.1 in
      6q27, and MPZL3 in 11q23.3). Besides, DVL3 (3q27.1), RP11-522I20.3 (9q21.32) and
      CCDC116 (22q11.21) were identified as novel lung cancer susceptibility genes.
      Pathway analysis showed that pathways involved in protein structure, the Notch
      signaling pathway and the nicotinic acetylcholine receptor-related pathways were
      associated with lung cancer risk. Combing eSNPs, gene- and pathway-based analysis
      identifies novel lung cancer susceptibility genes, which serves as a powerful
      approach to decipher biological mechanisms underlying GWAS findings.

PMID- 29193085
TI  - Elevated brain natriuretic peptide (BNP) is an early marker for patients at risk
      for complications after cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy (CRS + HIPEC).
AB  - BACKGROUND: Elevated BNP is associated with adverse cardiac outcomes after
      noncardiac surgery. We assessed BNP values as markers of perioperative fluid
      status and their correlation with major/cardiopulmonary (CP) complications
      following CRS + HIPEC. METHODS: Fluid balance, BNP levels, and morbidity data
      were collected for all patients undergoing CRS + HIPEC between 6/2014 and 2/2016.
      RESULTS: One hundred and twenty-nine patients underwent CRS + HIPEC for
      appendiceal adenocarcinoma (n = 99), mesothelioma (n = 16), and colon cancer (n =
      14). Less than 10% had CP comorbidities. The median PCI was 14 (range 4-39); 89%
      underwent CC0/1 resection (n = 115). Median blood loss (EBL) was 497 mL (50
      2700). Major complications (Clavien III-V) occurred in 16 (12%), CP in 17 (13%),
      and major/CP in 24 (18%). Thirty-day mortality occurred in 2 (1.5%). Elevated BNP
      on POD1 correlated with increased risk of major/CP complications (OR 2.2, P =
      0.052). This was most pronounced in the 25 patients receiving cisplatin: for each
      100 unit increase in POD1 BNP the OR for major/CP complication was 7.4 versus 1.2
      for the remaining patients, P = 0.083. Multivariate analysis identified increased
      EBL (OR 4.1 P = 0.011) and a trend toward increased BNP on POD1 (OR for each 100
      unit increase 2.0, P = 0.10) as risk factors for major/CP complications.
      CONCLUSIONS: Postoperative BNP measurement after CRS + HIPEC may guide
      postoperative fluid resuscitation and facilitate identification of patients at
      risk for major and/or cardiopulmonary complications.

PMID- 29193088
TI  - Ad Hoc Editors of Manuscripts.

PMID- 29193089
TI  - Recent Publications of Interest.

PMID- 29193086
TI  - Transfer rates of aflatoxins from herbal medicines to decoctions determined by an
      optimized high-performance liquid chromatography with fluorescence detection
      method.
AB  - OBJECTIVES: This study aimed to explore the transfer rates of aflatoxins from
      several contaminated herbal medicines by fungi to their decoctions. METHODS: Five
      types of commonly used herbal medicines including Lilii Bulbus, Hordei Fructus
      Germinatus, Nelumbinis Semen, Polygalae Radix and Bombyx Batryticatus were
      selected as the examples. Raw herbal medicine samples were treated by
      ultrasonication-assisted extraction with 70% methanol and immunoaffinity column
      clean-up, and the decoctions were prepared following the commonly used boiling
      method with water for 2 h. Then, the optimized high-performance liquid
      chromatography with fluorescence detection (HPLC-FLD) method was validated for
      the quantitative analysis of four aflatoxins (AFG2 , AFG1 , AFB2 and AFB1 ) after
      postcolumn photochemical derivatization, which was proved to be reliable and
      sensitive. KEY FINDINGS: Aflatoxins were detected to be transferred from the
      herbal medicines to decoctions with significantly different transfer rates in the
      five types of herbal medicines. Quietly high transfer rates of 7.26-115.36% for
      AFG2 , 4.37-26.37% for AFB1 and 9.64-47.68% for AFB2 were obtained. AFB1 as the
      most toxic aflatoxin expressed the lowest transfer rate, but still exhibited high
      amount in the samples. CONCLUSIONS: Therefore, the monitoring of aflatoxins in
      herbal medicines and their decoctions is in great urgency to ensure the security
      of consumers taking decoctions.

PMID- 29193090
TI  - Physiological stress responses to natural variation in predation risk: evidence
      from white sharks and seals.
AB  - Predators can impact ecosystems through consumptive or risk effects on prey.
      Physiologically, risk effects can be mediated by energetic mechanisms or stress
      responses. The predation-stress hypothesis predicts that risk induces stress in
      prey, which can affect survival and reproduction. However, empirical support for
      this hypothesis is both mixed and limited, and the conditions that cause
      predation risk to induce stress responses in some cases, but not others, remain
      unclear. Unusually clear-cut variation in exposure of Cape fur seals
      (Arctocephalus pusillus pusillus) to predation risk from white sharks
      (Carcharodon carcharias) in the waters of Southwestern Africa provides an
      opportunity to test the predation-stress hypothesis in the wild. Here, we
      measured fecal glucocorticoid concentrations (fGCM) from Cape fur seals at six
      discrete islands colonies exposed to spatiotemporal variation in predation risk
      from white sharks over a period of three years. We found highly elevated fGCM
      concentrations in seals at colonies exposed to high levels of unpredictable and
      relatively uncontrollable risk of shark attack, but not at colonies where seals
      were either not exposed to shark predation or could proactively mitigate their
      risk through antipredatory behavior. Differences in measured fGCM levels were
      consistent with patterns of risk at the site and seasonal level, for both seal
      adults and juveniles. Seal fGCM levels were not correlated with colony population
      size, density, and geographic location. Investigation at a high risk site (False
      Bay) also revealed strong correlations between fGCM levels and temporal variation
      in shark attack rates, but not with shark relative abundance. Our results suggest
      that predation risk will induce a stress response when risk cannot be predicted
      and/or proactively mitigated by behavioral responses.

PMID- 29193091
TI  - A novel three-way interaction among a fish, algae, and a parasitic copepod.

PMID- 29193092
TI  - Imaging in retroperitoneal soft tissue sarcoma.
AB  - Patients with retroperitoneal sarcoma can present to a variety of clinicians with
      non-specific symptoms and retroperitoneal sarcomas can be incidental findings.
      Failure to recognize retroperitoneal sarcomas on imaging can lead to
      inappropriate management in non-specialist centers. Therefore it is critical that
      the possibility of retroperitoneal sarcoma should be considered with prompt
      referral to a soft tissue sarcoma unit. This review guides clinicians through a
      diagnostic pathway, introduces concepts in response assessment and new imaging
      developments.

PMID- 29193093
TI  - Molecular adaptations of adipose tissue to 6 weeks of morning fasting vs. daily
      breakfast consumption in lean and obese adults.
AB  - KEY POINTS: In lean individuals, 6 weeks of extended morning fasting increases
      the expression of genes involved in lipid turnover (ACADM) and insulin signalling
      (IRS2) in subcutaneous abdominal adipose tissue. In obese individuals, 6 weeks of
      extended morning fasting increases IRS2 expression in subcutaneous abdominal
      adipose tissue. The content and activation status of key proteins involved in
      insulin signalling and glucose transport (GLUT4, Akt1 and Akt2) were unaffected
      by extended morning fasting. Therefore, any observations of altered adipose
      tissue insulin sensitivity with extended morning fasting do not necessarily
      require changes in insulin signalling proximal to Akt. Insulin-stimulated adipose
      tissue glucose uptake rates are lower in obese versus lean individuals, but this
      difference is abolished when values are normalised to whole-body fat mass. This
      suggests a novel hypothesis which proposes that the reduced adipose glucose
      uptake in obesity is a physiological down-regulation to prevent excessive de novo
      lipogenesis. ABSTRACT: This study assessed molecular responses of human
      subcutaneous abdominal adipose tissue (SCAT) to 6 weeks of morning fasting. Forty
      nine healthy lean (n = 29) and obese (n = 20) adults provided SCAT biopsies
      before and after 6 weeks of morning fasting (FAST; 0 kcal until 12.00 h) or daily
      breakfast consumption (BFAST; >=700 kcal before 11.00 h). Biopsies were analysed
      for mRNA levels of selected genes, and GLUT4 and Akt protein content. Basal and
      insulin-stimulated Akt activation and tissue glucose uptake rates were also
      determined. In lean individuals, lipid turnover and insulin signalling genes
      (ACADM and IRS2) were up-regulated with FAST versus BFAST (ACADM: 1.14 (95% CI:
      0.97-1.30) versus 0.80 (95% CI: 0.64-0.96), P = 0.007; IRS2: 1.75 (95% CI: 1.33
      2.16) versus 1.09 (95% CI: 0.67-1.51), P = 0.03, respectively). In obese
      individuals, no differential (FAST versus BFAST) expression was observed in genes
      involved in lipid turnover (all P > 0.1). GLUT4, Akt protein content and insulin
      stimulated Akt phosphorylation were unaffected by FAST versus BFAST in both lean
      and obese cohorts (all P > 0.1). Lower insulin-stimulated glucose uptake rates in
      obese versus lean individuals were eradicated when normalised to whole-body fat
      mass (P = 0.416). We conclude that morning fasting up-regulates lipid turnover
      genes in SCAT of lean individuals. Secondly, altered SCAT insulin sensitivity
      with morning fasting is unlikely to be explained by signalling proximal to Akt.
      Finally, lower insulin-stimulated SCAT glucose uptake rates in obese individuals
      are proportional to whole-body fat mass, suggesting a compensatory down
      regulation, presumably to prevent excessive de novo lipogenesis in adipose
      tissue. This trial was registered as ISRCTN31521726.

PMID- 29193094
TI  - Expression of programmed death-1 in sentinel lymph nodes of breast cancer.
AB  - BACKGROUND AND OBJECTIVES: To explore whether lymphocytes in sentinel lymph nodes
      (SLNs) are highly exposed to tumor neoantigens and thus express high level of
      programmed death 1 (PD-1), we examined PD-1 expression in SLNs and non-sentinel
      regional lymph nodes (non-SLNs) in breast cancer. METHODS: We performed PD-1
      immunohistochemistry in two cohorts: 40 metastasis-negative SLNs including 10
      patients for each subtype (luminal A-like, luminal B-like, HER2, and triple
      negative breast cancer [TNBC]); and 25 pairs of metastasis-positive SLNs and non
      SLNs (10 luminal A-like, 10 luminal B-like, and 5 TNBC). RESULTS: Among 40
      metastasis-negative SLNs, 34 and 6 samples were PD-1 intensity grade 1 (low) and
      2 (high), respectively. PD-1 intensity correlated with PD-1-positive lymphocyte
      numbers (P = 0.005); TNBC had the highest PD-1 lymphocyte numbers among all
      subtypes. The median PD-1-positive lymphocyte number was higher in SLNs than non
      SLNs. In most cases, more lymphocytes in SLNs expressed PD-1 than those in non
      SLNs (P < 0.0001). CONCLUSIONS: TNBC had the greatest PD-1 expression among all
      subtypes, and metastasis-positive SLNs had more PD-1-positive lymphocytes than
      downstream non-SLNs. These data suggested that lymphocytes in SLNs are activated
      following exposure to tumor neoantigens and thus tumor specific, and could be
      utilized as a biomarker platform.

PMID- 29193095
TI  - Real-time detection system for tumor localization during minimally invasive
      surgery for gastric and colon cancer removal: In vivo feasibility study in a
      swine model.
AB  - BACKGROUND AND OBJECTIVES: During minimally invasive surgery (MIS), it is
      impossible to directly detect marked clips around tumors via palpation.
      Therefore, we developed a novel method and device using Radio Frequency
      IDentification (RFID) technology to detect the position of clips during minimally
      invasive gastrectomy or colectomy. METHODS: The feasibility of the RFID-based
      detection system was evaluated in an animal experiment consisting of seven swine.
      The primary outcome was to successfully detect the location of RFID clips in the
      stomach and colon. The secondary outcome measures were to detect time (time
      during the intracorporeal detection of the RFID clip), and accuracy (distance
      between the RFID clip and the detected site). RESULTS: A total of 25 detection
      attempts (14 in the stomach and 11 in the colon) using the RFID antenna had a
      100% success rate. The median detection time was 32.5 s (range, 15-119 s) for the
      stomach and 28.0 s (range, 8-87 s) for the colon. The median detection distance
      was 6.5 mm (range, 4-18 mm) for the stomach and 6.0 mm (range, 3-13 mm) for the
      colon. CONCLUSIONS: We demonstrated favorable results for a RFID system that
      detects the position of gastric and colon tumors in real-time during MIS.

PMID- 29193096
TI  - Surgical treatment of pulmonic stenosis in dogs under cardiopulmonary bypass:
      outcome in nine dogs.
AB  - OBJECTIVES: To describe the outcome for nine dogs with pulmonic stenosis treated
      by open patch grafting using expanded polytetrafluoroethylene under
      cardiopulmonary bypass. MATERIALS AND METHODS: Data were collected from the
      hospital records of all dogs that had undergone right ventricular outflow tract
      grafting with an expanded polytetrafluoroethylene patch under cardiopulmonary
      bypass between 2006 and 2012 for the treatment of pulmonic stenosis.
      Echocardiographic images were reviewed and the pressure gradient across the right
      ventricular outflow tract re-measured. Owners of dogs still alive at the time of
      writing were invited to return to the hospital for reassessment. RESULTS: Nine
      dogs met the inclusion criteria. Median pressure gradient preoperatively was 118
      mmHg, (range 102 to 259 mmHg) reducing to a median of 20 mmHg (range 7 to 53
      mmHg) at 48 hours postoperatively and 14 mmHg (range 10 to 70 mmHg), with a
      median percentage reduction of 89% (range 41 to 94%) at long-term follow-up.
      Eight of nine dogs survived surgery, with six of nine surviving to hospital
      discharge. Two dogs were still alive over 6 and 8 years postoperatively. No long
      term deaths were believed to be attributable to pulmonic stenosis. CLINICAL
      SIGNIFICANCE: Expanded polytetrafluoroethylene patch grafting of the right
      ventricular outflow tract for treatment of severe pulmonic stenosis in dogs is
      feasible and can be an effective method to reduce the severity of right
      ventricular outflow tract obstruction.

PMID- 29193097
TI  - In vitro digestibility, free and bound phenolic profiles and antioxidant activity
      of thermally treated Eragrostis tef L.
AB  - BACKGROUND: Total phenolic content, phenolic profile and antioxidant activity
      were determined in free and bound phenolic fractions of thermally treated brown
      and white teff grains. RESULTS: Phenolic content in raw brown and white teff
      (1540 and 992 mg gallic acid equivalent kg-1 ) as well as antioxidant activity
      (6.3 and 5.5 mmol trolox equivalent kg-1 ) were higher in free phenolic
      fractions. The most significant decrease in total phenolics was observed after
      application of the sous-vide method (35% for brown teff and 11% for white teff).
      Main free phenolics of heat-treated teff were ferulic, protocatechuic, p-coumaric
      and ellagic acids, rutin and epigallocatechin. Main bound phenolics were ferulic,
      gallic, sinapic and ellagic acids, catechin and epigallocatechin. The detrimental
      effect on free and bound quercetin and bound cinnamic acid concentrations was
      also examined during heat treatment. Thermally treated brown teff showed a high
      level of in vitro organic matter digestibility if water cooking and rice cooker
      (both 99.5%) and sous-vide (96.5%) methods were applied. CONCLUSION: The sous
      vide method may be recommended as the most suitable hydrothermal treatment for
      grains of teff when compared with water cooking and rice cooker methods. (c) 2017
      Society of Chemical Industry.

PMID- 29193099
TI  - Cytologic findings of spindle epithelial tumor with thymus-like elements.
AB  - Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare and
      morphologically unique biphasic pediatric thyroid tumor of low malignant
      potential. There are less than 50 cases reported in the literature and few
      reported metastases. Despite the common usage of needle aspiration for thyroid
      and lymph node evaluation, cytologic descriptions of SETTLE are rare and tend to
      focus on a hypercellular biphasic appearance. We report aspirate findings of
      early cystic lymph node metastases in a 14-year-old girl, showing abundant matrix
      and low cellularity. We propose that the lack of recognition of this abundant
      matrix and cystic ultrasound appearance (as well as rarity of this tumor) may
      account for the low number of cytologic descriptions in the literature. Improved
      recognition may lead to increased usefulness of aspiration in the diagnosis and
      follow-up of SETTLE. Laryngoscope, 128:E78-E82, 2018.

PMID- 29193098
TI  - Factors associated with a primary surgical approach for sinonasal squamous cell
      carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Primary surgery is the preferred treatment of T1-T4a
      sinonasal squamous cell carcinoma (SNSCC). METHODS: Patients with SNSCC in the
      National Cancer Data Base (NCDB) were analyzed. Factors that contributed to
      selecting primary surgical treatment were examined. Overall survival (OS) in
      surgical patients was analyzed. RESULTS: Four-thousand seven hundred and seventy
      patients with SNSCC were included. In T1-T4a tumors, lymph node metastases,
      maxillary sinus location, and treatment at high-volume centers were associated
      with selecting primary surgery. When primary surgery was utilized, tumor factors
      and positive margin guided worse OS. Adjuvant therapy improved OS in positive
      margin resection and advanced T stage cases. CONCLUSIONS: Tumor and non-tumor
      factors are associated with selecting surgery for the treatment of SNSCC. When
      surgery is selected, tumor factors drive OS. Negative margin resection should be
      the goal of a primary surgical approach. When a positive margin resection ensues,
      adjuvant therapy may improve OS.

PMID- 29193101
TI  - Case series supporting heme detoxification via therapeutic plasma exchange in
      acute multiorgan failure syndrome resistant to red blood cell exchange in sickle
      cell disease.
AB  - BACKGROUND: Depletion of haptoglobin (Hp) and hemopexin (Hx) with increase in
      free hemoglobin and heme are important etiologies of vaso-occlusive complications
      in sickle cell disease (SCD). This study is the first to show an association
      between clinical improvement in SCD and repletion of Hp and Hx by therapeutic
      plasma exchange (TPE) using plasma replacement. STUDY DESIGN AND METHODS:
      Thirteen fresh-frozen plasma (FFP) units derived from consecutive whole blood
      donations were thawed at 37 degrees C after 10 months of storage; Hp and Hx
      concentrations immediately postthaw and after 5 days of refrigerated storage were
      analyzed by enzyme-linked immunosorbent assay (ELISA). All SCD patients
      presenting to a single institution over a 2-year period with acute multiorgan
      failure syndrome resistant to red blood cell exchange (RCE) were treated with TPE
      with FFP replacement; concentrations of Hp, Hx, and heme were evaluated before
      and after TPE by ELISA. RESULTS: Plasma concentrations of Hp and Hx decreased
      approximately 20% (p <= 0.002) after 5 days of refrigerated storage. Significant
      mean fold increases after TPE of 10 for Hp (p < 0.005) and seven for Hx (p <
      0.003) and a 30% mean decrease in heme concentrations (p = 0.07) were noted in
      association with clinical improvement (three patients), whereas minimal increases
      in Hp and Hx were associated with continued clinical deterioration in one
      patient. CONCLUSION: Fresh-frozen plasma rather than thawed plasma is optimal for
      Hp and Hx replacement. Patient data are consistent with Hp and Hx increases via
      TPE limiting clinical toxicity of worsened hemolysis associated with severe vaso
      occlusive complications refractory to RCE in SCD.

PMID- 29193102
TI  - Two novel mutations in KLF1 were identified in Chinese individuals with In(Lu)
      phenotype.

PMID- 29193103
TI  - Intravenous immunoglobulin-induced acute thrombocytopenia.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) has known efficacy in various
      hematologic conditions, including immune thrombocytopenic purpura. STUDY DESIGN
      AND METHODS: We present the clinical course of a patient with splenic marginal
      zone lymphoma, who developed acute thrombocytopenia on three consecutive
      episodes, with nadir counts of 27 * 109 , 50 * 109 , and 9 * 109 /L, upon
      administration of Intratect IVIG for hypogammaglobulinemia. An immunofluorescence
      test applying flow cytometry and monoclonal antibody immobilization of platelet
      antigens (MAIPA) assay were used to evaluate the reaction between IgG present in
      the IVIG preparations and the patient's or healthy donors' platelets (PLTs).
      RESULTS: A strong direct binding reaction was observed between the patient's PLTs
      and Intratect IgG using both methods. A similar reaction failed to materialize
      with controls. Binding was not antigen specific according to MAIPA. CONCLUSIONS:
      This is the first reported case of thrombocytopenia as a possible adverse effect
      of IVIG.

PMID- 29193105
TI  - Correlations between cystic fibrosis genotype and sinus disease severity in
      chronic rhinosinusitis.
AB  - OBJECTIVE: Cystic fibrosis (CF) patients commonly develop chronic rhinosinusitis
      (CRS). The impact of the most common cystic fibrosis transmembrane conductance
      regulator (CFTR) mutation, F508del, on the severity of sinonasal disease remains
      inconclusive. The objective of this study is to evaluate the impact of CFTR
      genotype functional classification on sinonasal disease severity in patients with
      CRS. METHODS: Retrospective chart review of patients with CF who underwent
      endoscopic sinus surgery for chronic rhinosinusitis from 1998 to 2015. Patients
      were divided into high- or low-risk genotypes based on standardized CFTR gene
      functional classification. The primary outcome was the 22-item Sino-Nasal Outcome
      Test (SNOT-22) score. Secondary outcomes included endoscopic scores, extent of
      surgery performed, presence of polyposis, number of revision surgeries, and Lund
      MacKay computed tomography scores. RESULTS: Thirty-eight patients harbored a high
      risk CFTR genotype, and 11 had a low-risk genotype. On bivariate analysis, there
      was no association between CFTR genotype risk stratification and measures of
      preoperative disease severity or postoperative outcomes. There were no
      associations between genotype risk stratification and outcome variables on
      multivariate linear regression, adjusted for age and gender. There were
      significant improvements in several SNOT-22 subdomains before and after
      endoscopic sinus surgery (P < 0.05), but the magnitude of improvement was not
      significantly different on the basis of CFTR genotype risk stratification.
      CONCLUSION: High-risk CFTR genotypes are not associated with worse sinonasal
      disease severity or postoperative symptom control than low-risk CFTR genotypes
      after adjusting for confounding factors. LEVEL OF EVIDENCE: Level 4.
      Laryngoscope, 1752-1758, 2018.

PMID- 29193104
TI  - Transfusion strategy for weak D Type 4.0 based on RHD alleles and RH haplotypes
      in Tunisia.
AB  - BACKGROUND: With more than 460 RHD alleles, this gene is the most complex and
      polymorphic among all blood group systems. The Tunisian population has the
      largest known prevalence of weak D Type 4.0 alleles, occurring in one of 105 RH
      haplotypes. We aimed to establish a rationale for the transfusion strategy of
      weak D Type 4.0 in Tunisia. STUDY DESIGN AND METHODS: Donors were randomly
      screened for the serologic weak D phenotype. The RHD coding sequence and parts of
      the introns were sequenced. To establish the RH haplotype, the RHCE gene was
      tested for characteristic single-nucleotide positions. RESULTS: We determined all
      RHD alleles and the RH haplotypes coding for the serologic weak D phenotype among
      13,431 Tunisian donations. A serologic weak D phenotype was found in 67
      individuals (0.50%). Among them, 60 carried a weak D Type 4 allele: 53 weak D
      Type 4.0, six weak D Type 4.2.2 (DAR), and one weak D Type 4.1. An additional
      four donors had one variant allele each: DVII, weak D Type 1, weak D Type 3, and
      weak D type 100, while three donors showed a normal RHD sequence. The weak D Type
      4.0 was most often linked to RHCE*ceVS.04.01, weak D Type 4.2.2 to RHCE*ceAR, and
      weak D Type 4.1 to RHCE*ceVS.02, while the other RHD alleles were linked to one
      of the common RHCE alleles. CONCLUSIONS: Among the weak D phenotypes in Tunisia,
      no novel RHD allele was found and almost 90% were caused by alleles of the weak D
      Type 4 cluster, of which 88% represented the weak D Type 4.0 allele. Based on
      established RH haplotypes for variant RHD and RHCE alleles and the lack of
      adverse clinical reports, we recommend D+ transfusions for patients with weak D
      Type 4.0 in Tunisia.

PMID- 29193106
TI  - Who's afraid of incompatible plasma? A balanced approach to the safe transfusion
      of blood products containing ABO-incompatible plasma.

PMID- 29193107
TI  - Characteristics of the water footprint of rice production under different
      rainfall years in Jilin Province, China.
AB  - BACKGROUND: Rice is a special crop, and its production differs from that of other
      crops because it requires a thin layer of water coverage for a long period. The
      calculation of the water footprint of rice production should differ from that of
      other crops owing to the rice growing process. This study improved the
      calculation of blue and grey water footprints of rice production and analyzed the
      variations in the water footprints for rice production under different rainfall
      years in Jilin Province. RESULTS: In the drought year, the green water footprint
      was the lowest and the blue water footprint was the highest among the three
      years, while in the humid year, the green water footprint was the highest and the
      blue water footprint was not the lowest. The areas with higher water footprints
      were found in the east and west regions of Jilin Province, while the areas with
      lower water footprints were found in the middle east and middle regions of Jilin
      Province. CONCLUSION: Blue water was the primary water resource for rice
      production, although more precipitation provided the highest green water in the
      humid year; also, the spatial distributions of water footprints were not the same
      under different rainfall years. (c) 2017 Society of Chemical Industry.

PMID- 29193108
TI  - Impact of untreated dental caries on the daily activities of children.
AB  - OBJECTIVES: Untreated dental caries can compromise oral health-related quality of
      life (OHRQoL). However, it is not clear which specific daily activities related
      to OHRQoL are compromised by the presence of this problem. Therefore, the purpose
      of this study was to identify which specific daily activities are affected by the
      presence of untreated dental caries using a representative sample of Brazilian
      children. METHODS: A cross-sectional study using a representative sample of
      Brazilian children (12 years of age) was conducted. The presence of untreated
      dental caries was assessed using the "decayed - D" component of the DMFT
      (decayed, missing, and filled teeth) index. Clinical exams were conducted by
      trained and calibrated dentists. The daily activities were evaluated using the
      survey Oral Impacts on Daily Performance (OIDP), considering items and domains.
      Descriptive, bivariate, and multiple analyses were conducted (alpha = 0.05).
      RESULTS: A total of 7,247 children were included, and 39.9 percent had at least
      one tooth with untreated dental caries, with 33.5 percent experiencing an impact
      on at least one of the OIDP activities. This study identified a greater chance of
      the presence of untreated dental caries in children having an impact on the
      psychological domain (P = 0.006), as well as on the "difficulty eating" (P =
      0.007), and "difficulty sleeping" (P = 0.023) items. CONCLUSION: The presence of
      untreated dental caries among Brazilian children was associated with an impact on
      specific daily activities (difficulty eating and sleeping) and the psychological
      domain of OHRQoL.

PMID- 29193109
TI  - Skeletal Trauma Resulting From Fatal Low (<=3 m) Free Falls: An Analysis of
      Fracture Patterns and Morphologies.
AB  - The skeletal trauma resulting from fatal low (<=3 m) free falls is poorly
      researched and understood by forensic practitioners. The aim of this study was to
      identify the types of skeletal trauma resulting from low falls through
      investigating fracture patterns and morphologies. Skeletal trauma was analyzed
      using full-body postmortem computed tomography scans of 145 individuals who died
      from a low free fall. Trauma was then contextualized to the variables that
      influence how a person falls using multiple logistic regression. Results showed
      fracture patterning primarily involved the axial skeleton and that there were a
      number of patterns significantly associated with the height fallen, pre-existing
      health conditions, and age. Analysis of fracture morphologies showed 108 possible
      fracture types, six of which were significantly associated with the height
      fallen. Understanding the skeletal trauma characteristic of low free falls will
      further inform anthropological interpretations of trauma in cases where a fall
      may be considered the possible mechanism.

PMID- 29193110
TI  - Tinnitus and its risk factors in african americans: The Jackson Heart Study.
AB  - OBJECTIVES/HYPOTHESIS: To describe the prevalence of reported tinnitus and
      tinnitus handicap in the all-African American Jackson Heart Study (JHS) cohort,
      with assessment of the relationship to cardiometabolic risk and depression. STUDY
      DESIGN: Prospective cohort study. METHODS: Audiologic data were obtained from a
      sample of 1,314 participants of the JHS. Reported tinnitus was assessed
      dichotomously (yes/no) by interview and with the Tinnitus Handicap Inventory
      (THI). The statistical relationship of reported tinnitus and tinnitus handicap to
      various cardiometabolic risks (i.e., hypertension and waist circumference) and
      Center for Epidemiologic Studies Depression scale (CES-D) was assessed with
      logistic and gamma regression procedures. RESULTS: Tinnitus was found to be a
      highly prevalent condition (29.5%), with an additionally high rate of individuals
      who report at least slight tinnitus handicap (35%). Hypertension (beta = 1.344,
      95% confidence interval [CI]: 1.015-1.780, P = .039) and waist circumference
      (beta = 1.009, 95% CI: 1.001-1.018, P = .021) were found to have a statistically
      significant relationship with THI score, depending on the level of covariate
      adjustment. Depression, as measured by the CES-D, was found to have a
      statistically significant relationship with both reported tinnitus (odds ratio
      [OR]: 1.051, 95% CI: 1.030-1.072, P < .001) and THI score (beta = 1.029, 95% CI:
      1.013-1.047, P = .001), which persisted for all levels of covariate adjustment in
      statistical models. CONCLUSIONS: Tinnitus was found to be highly prevalent in the
      JHS, and certain measures of cardiometabolic risk are weakly related to both
      reported tinnitus and level of tinnitus handicap. A consistent relationship
      between depression and tinnitus/level of tinnitus handicap was observed. LEVEL OF
      EVIDENCE: 2b. Laryngoscope, 128:1668-1675, 2018.

PMID- 29193112
TI  - Prevalence of adult unilateral hearing loss and hearing aid use in the United
      States.
AB  - OBJECTIVE: The prevalence of unilateral hearing loss (UHL) in adults has not been
      well characterized. The objectives of this study are to determine the prevalence
      of UHL in U.S. adults and its treatment with hearing aids using a nationally
      representative study. STUDY DESIGN: Cross-sectional national epidemiologic study
      (n = 6,242). METHODS: Subjects >= 18 years old with audiometric testing in the
      2005 to 2006, 2009 to 2010, and 2011 to 2012 cycles of the National Health and
      Nutrition Examination Study were included. UHL was defined as normal hearing
      (<=25 decibels hearing level [dB HL] pure tone average [PTA]) in one ear and at
      least mild hearing loss (>25 dB HL PTA) in the other ear. Hearing aid usage was
      defined by at least 5 hours per week (2005-2006) or at least seldom (2009-2012)
      use. Sampling weights were utilized to ensure generalizability to the U.S.
      POPULATION:  RESULTS: The overall prevalence of UHL in adult Americans was 7.2%
      (95% confidence interval 6.1%-8.6%), with 5.7% (4.8%-6.7%) having mild and 1.5%
      (0.1%-2.1%) with moderate-or-worse UHL; nearly one-third of the latter reported
      trouble hearing. The prevalence of hearing aid usage in those with UHL was 2.0%
      (0.6%-6.7%). Of those with mild UHL, 1.4% (0.2%-8.0%) used hearing aids. Of those
      with moderate UHL, 4.2% (0.1%-22%) used hearing aids. Among those with UHL and
      also at least moderate subjective difficulty hearing, only 11% wore hearing aids.
      CONCLUSION: UHL is common among U.S. adults. Hearing aid usage is very low, even
      when there is perceived handicap. Public health education is needed to increase
      awareness of and auditory rehabilitation for UHL. LEVEL OF EVIDENCE: 2.
      Laryngoscope, 128:1681-1686, 2018.

PMID- 29193111
TI  - Clinical input of anti-D quantitation by continuous-flow analysis on autoanalyzer
      in the management of high-titer anti-D maternal alloimmunization.
AB  - BACKGROUND: In addition to titration by indirect antiglobulin test most widely
      used, anti-D quantitation by continuous-flow analysis (CFA) may be performed to
      assess severity of maternal immunization. Only five studies have reported its
      added value in the management of pregnancies complicated by anti-D immunization.
      STUDY DESIGN AND METHODS: A retrospective study of 74 severe anti-D-immunized
      pregnancies was conducted from January 1, 2013, to December 31, 2014, in the
      Trousseau Hospital in Paris (France). Concentration of maternal anti-D was
      measured by titration and by CFA two-stages method (2SM; total amount of anti-D)
      and one-stage method (1SM; high-affinity IgG1 anti-D). These biologic data were
      analyzed according to the severity of the hemolytic disease of the fetus and the
      newborn. RESULTS: The value of 5 IU anti-D/mL in maternal serum is validated as a
      threshold to trigger ultrasonographic and Doppler fetal close follow-up. A high
      1SM/2SM ratio was associated with a higher risk of intrauterine transfusion
      (IUT). For pregnancies requiring IUT and without increasing titer, maternal 1SM
      anti-D concentration tends to correlate with the precocity of fetal anemia. In
      the "without-IUT" group 1SM and 2SM anti-D concentrations correlate significantly
      with cord bilirubin levels of the newborn at birth. CONCLUSION: Altogether our
      results underline the importance of anti-D quantitation by CFA to optimize the
      management of anti-D-alloimmunized pregnancies.

PMID- 29193113
TI  - Globalizing health policy.

PMID- 29193115
TI  - International Council of Nurses congratulates first cohort of graduates from
      Global Nursing Policy Leadership Institute.

PMID- 29193114
TI  - International Council of Nurses' growth, development and engagement.

PMID- 29193116
TI  - Nursing ethics, disasters and public emergencies.

PMID- 29193117
TI  - The development of D antibodies after D-mismatched kidney transplantation in a
      setting of reduced immunosuppression.
AB  - BACKGROUND: D antigens are not taken into account in the allocation of solid
      organs. Female transplant recipients with D antibodies as a consequence of D
      mismatched kidney transplantation may develop hemolytic disease of the fetus and
      newborn in future pregnancies. We examined D antibody development in transplant
      recipients who received D-mismatched kidney transplantation in absence of D
      prophylaxis and in a setting of reduced immunosuppression. STUDY DESIGN AND
      METHODS: From 1993 until 2015, a total of 1355 kidney patients received
      transplantations in our center of whom 156 received a D-mismatched graft. A
      retrospective analysis was conducted; frozen stored sera obtained from transplant
      recipients 3 months after transplantation were tested for irregular red blood
      cell (RBC) antibodies using a three-cell screening and an identification panel.
      In the case of D antibody positivity, additional testing was performed 1 month
      before transplantation. RESULTS: In seven of 156 (4.5%) transplant recipients we
      found irregular RBC antibodies after transplantation, of which five (3.2%) were
      determined to be D antibodies. We observed only one (0.6%) recipient without D
      antibodies before transplantation. CONCLUSION: Although the risk of D antibody
      development is considerably lower after D-mismatched kidney transplantation than
      D-mismatched pregnancy, anti-D prophylaxis may still be advisable for female
      transplant recipients of childbearing age.

PMID- 29193118
TI  - In premature infants there is no decrease in 24-hour posttransfusion allogeneic
      red blood cell recovery after 42 days of storage.
AB  - BACKGROUND: Critically ill preterm very-low-birthweight (VLBW) neonates
      (birthweight <= 1.5 kg) frequently develop anemia that is treated with red blood
      cell (RBC) transfusions. Although RBCs transfused to adults demonstrate
      progressive decreases in posttransfusion 24-hour RBC recovery (PTR24 ) during
      storage-to a mean of approximately 85% of the Food and Drug Administration
      allowed 42-day storage-limited data in infants indicate no decrease in PTR24 with
      storage. STUDY DESIGN AND METHODS: We hypothesized that PTR24 of allogeneic RBCs
      transfused to anemic VLBW newborns: 1) will be greater than PTR24 of autologous
      RBCs transfused into healthy adults and 2) will not decrease with increasing
      storage duration. RBCs were stored at 4 degrees C for not more than 42 days in AS
      3 or AS-5. PTR24 was determined in 46 VLBW neonates using biotin-labeled RBCs and
      in 76 healthy adults using 51 Cr-labeled RBCs. Linear mixed-model analysis was
      used to estimate slopes and intercepts of PTR24 versus duration of RBC storage.
      RESULTS: For VLBW newborns, the estimated slope of PTR24 versus storage did not
      decrease with the duration of storage (p = 0.18) while for adults it did (p <
      0.0001). These estimated slopes differed significantly in adults compared to
      newborns (p = 0.04). At the allowed 42-day storage limit, projected mean neonatal
      PTR24 was 95.9%; for adults, it was 83.8% (p = 0.0002). CONCLUSIONS: These data
      provide evidence that storage duration of allogeneic RBCs intended for neonates
      can be increased without affecting PTR24 . This conclusion supports the practice
      of transfusing RBCs stored up to 42 days for small-volume neonatal transfusions
      to limit donor exposure.

PMID- 29193119
TI  - Evaluation of the applicability and effectiveness of a molecular strategy for
      identifying weak D and DEL phenotype among D- blood donors of mixed origin
      exhibiting high frequency of RHD*Psi.
AB  - BACKGROUND: Molecular tests designed to detect the presence of active RHD gene
      among D- donors have been successfully applied in people of European ancestry,
      but not in admixed populations with a considerable frequency of RHD*Psi. Our goal
      was to evaluate the performance of a molecular screening tool for identifying
      active RHD alleles among Brazilian blood donors classified as D- C+ and/or E+.
      STUDY DESIGN AND METHODS: Pools of five DNA samples of serologically D- C+ and/or
      E+ donors were checked by a RHD polymerase chain reaction (PCR) assay specific
      for RHD Intron 4 and Exon 7. When a pool result was positive, samples were
      genotyped individually for RHD Intron 4 and Exon 7, RHD*Psi, RHCE*Cc, and RHD
      zygosity. Donors suspected of active RHD gene were further evaluated by whole
      coding region and flanking intron direct sequencing. RESULTS: A total of 405
      donors were included. Two percent exhibited active RHD gene, codifying D-weak (38
      and 45) or DEL phenotype. The most prevalent DEL allele was RHD*DEL1 (c.1227G>A),
      which is proven to be immunogenic. A high frequency of RHD*Psi was detected in
      the donors with nondeleted RHD alleles (31%), far superior to the frequency of
      RHD variant alleles (15.5%). The proposed approach presented sensitivity of 100%
      and specificity of 85.7% for identifying active RHD gene. CONCLUSION: The
      strategy of checking D- donors with RHD PCR followed by exclusion of RHD*Psi
      allele has proved efficient in identifying weak-D and DEL phenotype in the
      Brazilian population.

PMID- 29193120
TI  - The role of elective neck dissection in the treatment of maxillary sinus squamous
      cell carcinoma.
AB  - OBJECTIVE: This study is designed to analyze the survival benefits of elective
      neck dissection (END) in the treatment of squamous cell carcinoma of the
      maxillary sinus (MS-SCC) with clinically negative neck lymph nodes (N0) and no
      metastasis (M0). STUDY DESIGN: The aim of this study was to evaluate whether END
      improves survival in patients with MS-SCC. METHODS: This study is a population
      based, concurrent retrospective database analysis of patients diagnosed with N0M0
      MS-SCC from 2004 to 2013. Data were acquired from the Surveillance, Epidemiology,
      and End Results database. Frequency functions, Kaplan-Meier and Cox regression
      models were queried to analyze demographics, treatment status, and survival
      outcomes. RESULTS: There were a total of 927 MS-SCC cases in the database between
      2004 and 2013. This analysis revealed that for the overall cohort, END
      significantly and independently reduces the 5-year hazard of death in MS-SCC
      (hazard ratio [HR] = 0.646, 95% confidence interval [CI] = 0.419-0.873, P =
      0.047). For early tumor (T)1/T2 tumors and T4 tumors, END did not independently
      improve 5-year survival. However, for T3 disease, END significantly reduced the 5
      year hazard of death in MS-SCC (HR = 0.471, 95% CI = 0.261-0.680, P = 0.001),
      regardless of other covariates, including adjuvant radiation. There has been an
      increase in the percentage of MS-SCC surgeries that have been accompanied by END
      since SEER started collecting this data, although this did not demonstrate
      significance (R2 = 0.622). CONCLUSION: END improves disease-specific survival in
      patients with MS-SCC size > 4 cm and advanced T-stage (American Joint Committee
      on Cancer AJCC TIII). Therefore, surgeons performing maxillectomies should
      consider conducting an END concurrent with maxillectomy for those with size > 4
      cm advanced stage cancer. LEVEL OF EVIDENCE: 4. Laryngoscope, 1835-1841, 2018.

PMID- 29193121
TI  - On the recalcitrant use of Arnon's method for chlorophyll determination.

PMID- 29193122
TI  - Post-fire effects in xylem hydraulics of Picea abies, Pinus sylvestris and Fagus
      sylvatica.
AB  - Recent studies on post-fire tree mortality suggest a role for heat-induced
      alterations of the hydraulic system. We analyzed heat effects on xylem hydraulics
      both in the laboratory and at a forest site hit by fire. Stem vulnerability to
      drought-induced embolism and hydraulic conductivity were measured in Picea abies,
      Pinus sylvestris and Fagus sylvatica. Control branches were compared with samples
      experimentally exposed to 90 degrees C or damaged by a natural forest fire. In
      addition, xylem anatomical changes were examined microscopically. Experimental
      heating caused structural changes in the xylem and increased vulnerability in all
      species. The largest shifts in vulnerability thresholds (1.3 MPa) were observed
      in P. sylvestris. F. sylvatica also showed heat-induced reductions (49%) in
      hydraulic conductivity. At the field site, increased vulnerability was observed
      in damaged branches of P. sylvestris and F. sylvatica, and the xylem of F.
      sylvatica was 39% less conductive in damaged than in undamaged branches. These
      results provide evidence for heat-induced impairment of tree hydraulics after
      fire. The effects recorded at the forest fire site corresponded to those obtained
      in laboratory experiments, and revealed pronounced hydraulic risks in P.
      sylvestris and F. sylvatica. Knowledge of species-specific hydraulic impairments
      induced by fire and heat is a prerequisite for accurate estimation of post-fire
      mortality risks.

PMID- 29193123
TI  - Physiologically Based Pharmacokinetic Modeling to Evaluate the Systemic Exposure
      of Gefitinib in CYP2D6 Ultrarapid Metabolizers and Extensive Metabolizers.
AB  - Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR)
      tyrosine kinase and is used for the treatment of non-small-cell lung cancer
      (NSCLC) with activating EGFR mutations. Gefitinib is metabolized by CYP2D6 and
      CYP3A4. This analysis compared the systemic exposure of gefitinib after oral
      administration in CYP2D6 ultrarapid metabolizers (UM) vs extensive metabolizers
      (EM). Physiologically based pharmacokinetic (PBPK) modeling was conducted using a
      population-based simulator. The model was calibrated using itraconazole-gefitinib
      clinical drug-drug interaction data and validated with gefitinib data in CYP2D6
      EM vs poor metabolizers (PM). System components of the PBPK model were evaluated
      using published clinical metoprolol pharmacokinetic data in CYP2D6 UM, EM, and
      PM. Our PBPK model predicted a gefitinib geometric least-squares mean area under
      the plasma concentration-time curve (AUC) from time 0 to 264 hours (AUC(0-264) )
      ratio in the presence vs absence of itraconazole of 1.85, similar to the ratio of
      1.78 from clinical study data. Predicted and observed metoprolol geometric least
      squares mean AUC(0-24) ratios in UM vs EM were also similar (0.46 and 0.55,
      respectively), suggesting that system components related to CYP2D6 in the PBPK
      model were properly established. In addition, the PBPK model also captured
      gefitinib pharmacokinetic profiles in CYP2D6 polymorphic populations. The final
      PBPK model predicted a decrease in gefitinib AUC of ~39% in CYP2D6 UM vs EM. Such
      changes in exposure will have limited impact as the reduced exposure is still
      above gefitinib's in vitro IC90 for EGFR activating mutations in NSCLC patients.

PMID- 29193124
TI  - Prediction of benzo[a]pyrene content of smoked sausage using back-propagation
      artificial neural network.
AB  - BACKGROUND: Benzo[a]pyrene (BaP), a potent mutagen and carcinogen, is reported to
      be present in processed meat products and, in particular, in smoked meat.
      However, few methods exist for predictive determination of the BaP content of
      smoked meats such as sausage. In this study, an artificial neural network (ANN)
      model based on the back-propagation (BP) algorithm was used to predict the BaP
      content of smoked sausage. RESULTS: The results showed that the BP network based
      on the Levenberg-Marquardt algorithm was the best suited for creating a nonlinear
      map between the input and output parameters. The optimal network structure was 3
      7-1 and the learning rate was 0.6. This BP-ANN model allowed for accurate
      predictions, with the correlation coefficients (R) for the experimentally
      determined training, validation, test and global data sets being 0.94, 0.96, 0.95
      and 0.95 respectively. The validation performance was 0.013, suggesting that the
      proposed BP-ANN may be used to predictively detect the BaP content of smoked meat
      products. CONCLUSION: An effective predictive model was constructed for
      estimation of the BaP content of smoked sausage using ANN modeling techniques,
      which shows potential to predict the BaP content in smoked sausage. (c) 2017
      Society of Chemical Industry.

PMID- 29193125
TI  - Elevated ozone concentration decreases whole-plant hydraulic conductance and
      disturbs water use regulation in soybean plants.
AB  - Elevated tropospheric ozone (O3 ) concentration has been shown to affect many
      aspects of plant performance including detrimental effects on leaf photosynthesis
      and plant growth. However, it is not known whether such changes are accompanied
      by concomitant responses in plant hydraulic architecture and water relations,
      which would have great implications for plant growth and survival in face of
      unfavorable water conditions. A soybean (Glycine max (L.) Merr.) cultivar
      commonly used in Northeast China was exposed to non-filtered air (NF, averaged
      24.0 nl l-1 ) and elevated O3 concentrations (eO3 , 40 nl l-1 supplied with NF
      air) in six open-top chambers for 50 days. The eO3 treatment resulted in a
      significant decrease in whole-plant hydraulic conductance that is mainly
      attributable to the reduced hydraulic conductance of the root system and the
      leaflets, while stem and leaf petiole hydraulic conductance showed no significant
      response to eO3 . Stomatal conductance of plants grown under eO3 was lower during
      mid-morning but significantly higher at midday, which resulted in substantially
      more negative daily minimum water potentials. Moreover, excised leaves from the
      eO3 treated plants showed significantly higher rates of water loss, suggesting a
      lower ability to withhold water when water supply is impeded. Our results
      indicate that, besides the direct detrimental effects of eO3 on photosynthetic
      carbon assimilation, its influences on hydraulic architecture and water relations
      may also negatively affect O3 -sensitive crops by deteriorating the detrimental
      effects of unfavorable water conditions.

PMID- 29193126
TI  - Pharmacokinetics and Pharmacodynamics of Azeloprazole Sodium, a Novel Proton Pump
      Inhibitor, in Healthy Japanese Volunteers.
AB  - The pharmacokinetics (PK) and pharmacodynamics (PD) of proton pump inhibitors
      differ among cytochrome P450 (CYP) 2C19 genotypes. Therefore, we developed
      azeloprazole sodium (Z-215), a novel proton pump inhibitor, whose metabolism is
      not affected by CYP2C19 activity in vitro. However, the PK and PD of azeloprazole
      sodium have not been evaluated in Japanese subjects. We conducted an open-label,
      crossover study in healthy Japanese male volunteers to evaluate the plasma
      concentration and intragastric pH with respect to CYP2C19 genotype after repeated
      administration of 10, 20, and 40 mg azeloprazole sodium and 10 and 20 mg
      rabeprazole sodium (rabeprazole). The plasma concentration profile of
      azeloprazole sodium was similar among genotypes, whereas that of rabeprazole
      differed. The 24-hour intragastric pH >= 4 holding time ratio (pH >= 4 HTR) of
      azeloprazole sodium was similar among genotypes. The pH >= 4 HTR was 52.5%-60.3%,
      55.1%-65.8%, and 69.4%-77.1% after administration of 10, 20, and 40 mg
      azeloprazole sodium, respectively, and 59.2%-72.3% and 64.4%-91.2% after
      administration of 10 and 20 mg rabeprazole, respectively, on the fifth day of
      dosing. The maximum plasma concentration (Cmax ), area under the plasma
      concentration-time curve (AUC), and pH >= 4 HTR of azeloprazole sodium were
      proportional to dose. The Cmax , AUC, and pH >= 4 HTR on day 5 were slightly
      higher following administration of 20 mg azeloprazole sodium before comparison
      with after a meal. No serious adverse events were observed. These results suggest
      that azeloprazole sodium is useful for treating gastroesophageal reflux disease
      in all CYP2C19 genotypes.

PMID- 29193127
TI  - Pregnancy and perinatal conditions and atopic disease prevalence in childhood and
      adulthood.
AB  - BACKGROUND: Previous studies showed controversial results for the influence of
      pregnancy-related and perinatal factors on subsequent respiratory and atopic
      diseases in children. The aim of this study was to assess the association between
      perinatal variables and the prevalence of asthma, bronchial hyperreactivity
      (BHR), flexural eczema (FE), allergic rhinitis, and sensitization in childhood
      and early adulthood. METHODS: The studied population was first examined in Munich
      and Dresden in 1995/1996 at age 9-11 years. Participants were followed until age
      19-24 years using questionnaires and clinical examinations. Associations between
      perinatal data and subsequent atopic diseases were examined using logistic
      regression analyses adjusting for potential confounders. RESULTS: Cesarean
      section was statistically significantly associated with BHR in early adulthood
      (odds ratio 4.8 [95% confidence interval 1.5-15.2]), while assisted birth was
      associated with presence of asthma symptoms in childhood (2.2 [1.2-3.9]), FE
      symptoms (2.2 [1.2-4.3]) and doctor's diagnosis of atopic dermatitis (1.9 [1.0
      3.4]) in childhood, and sensitization in early adulthood (2.2 [1.1-4.3]). Lower
      birth length (1.9 [1.1-3.2]), lower birthweight (0.5 [0.3-0.9]), and higher
      birthweight (0.6 [0.4-1.0]) were predictive of sensitization in early adulthood
      compared to average birth length and birthweight, respectively. None of the other
      perinatal factors showed statistically significant associations with the
      outcomes. CONCLUSIONS: Our results indicate that children who are born by
      cesarean section and especially by assisted birth, might be at greater risk for
      developing asthma, FE, and sensitization and should hence be monitored. Prenatal
      maternal stress might partly explain these associations, which should be further
      investigated.

PMID- 29193128
TI  - Pathogen reduction and blood transfusion safety in Africa: strengths, limitations
      and challenges of implementation in low-resource settings.
AB  - Transfusion-transmitted infection risk remains an enduring challenge to blood
      safety in Africa. A high background incidence and prevalence of the major
      transfusion-transmitted infections (TTIs), dependence on high-risk donors to meet
      demand, suboptimal testing and quality assurance collectively contribute to the
      increased risk. With few exceptions, donor testing is confined to serological
      evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV)
      and syphilis. Barriers to implementation of broader molecular methods include
      cost, limited infrastructure and lack of technical expertise. Pathogen reduction
      (PR), a term used to describe a variety of methods (e.g. solvent detergent
      treatment or photochemical activation) that may be applied to blood following
      collection, offers the means to diminish the infectious potential of multiple
      pathogens simultaneously. This is effective against different classes of
      pathogen, including the major TTIs where laboratory screening is already
      implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet
      remain unaddressed (e.g. malaria, bacterial contamination). We sought to review
      the available and emerging PR techniques and their potential application to
      resource-constrained parts of Africa, focusing on the advantages and
      disadvantages of such technologies. PR has been slow to be adopted even in high
      income countries, primarily given the high costs of use. Logistical
      considerations, particularly in low-resourced parts of Africa, also raise
      concerns about practicality. Nonetheless, PR offers a rational, innovative
      strategy to contend with TTIs; technologies in development may well present a
      viable complement or even alternative to targeted screening in the future.

PMID- 29193129
TI  - A model observer study using acquired mammographic images of an anthropomorphic
      breast phantom.
AB  - PURPOSE: To study the feasibility of a task-based framework composed of an
      anthropomorphic breast phantom and mathematical model observers (MOs) for the
      evaluation of system-processed mammographic images. METHODS: A prototype
      anthropomorphic breast phantom with inserted gold discs of 0.1 mm and 0.25 mm
      diameter was imaged with two digital mammography systems (system A and B) at four
      different dose levels. From the acquired processed and unprocessed images, signal
      present and signal-absent regions of interest (ROIs) were extracted. The ROIs
      were evaluated by a non-pre-whitening MO with eye filter (NPWE) and by three
      human observers in a two-alternative forced-choice experiment. We compared the
      human and the MO performance on a simple detection task of the calcification-like
      discs in ROIs with and without postprocessing. Proportion of correct responses of
      the human (PCH ) and NPWE (PCNPWE ) experiments was calculated and the
      correlation between the two was analyzed using a mixed-effect regression model.
      Correlation results including the goodness of fit (r2 ) of PCH and PCNPWE for all
      different parameters investigated were evaluated to determine whether NPWE MO can
      be used to predict human observer performance. RESULTS: PCH and PCNPWE increased
      with dose for all conditions investigated (signal size, processing status, and
      different system). In case of the 0.1 mm discs, for system A, r2 between PCH with
      PCNPWE was 0.81. For system B, r2 was 0.93. In case of the 0.25 mm discs, r2 in
      system A was 0.79 and for system B, r2 was 0.82. For the combined parameters
      investigated, and after excluding the 0.1 mm discs on system A because the
      results were influenced by aliasing, the overall r2 was 0.81. Image processing
      did not affect the detectability of calcification-like signals. No significant
      difference (P > 0.05) was found between the predicted PCH(pred) by the MO and the
      PCH for all different conditions. CONCLUSIONS: The framework seems promising to
      be used in objective image quality assessment. It was found to be relatively
      robust for the range of parameters investigated. However, further optimization of
      the anthropomorphic breast phantom and investigation of other MOs for a broader
      range of image quality assessment tasks is needed.

PMID- 29193130
TI  - Evaluation of a lateral flow-based technology card for blood typing using a
      simplified protocol in a model of extreme blood sampling conditions.
AB  - BACKGROUND: Life-threatening situations requiring blood transfusion under extreme
      conditions or in remote and austere locations, such as the battlefield or in
      traffic accidents, would benefit from reliable blood typing practices that are
      easily understood by a nonscientist or nonlaboratory technician and provide quick
      results. STUDY DESIGN AND METHODS: A simplified protocol was developed for the
      lateral flow-based device MDmulticard ABO-D-Rh subgroups-K. Its performance was
      compared to a reference method (PK7300, Beckman Coulter) in native blood samples
      from donors. The method was tested on blood samples stressed in vitro as a model
      of hemorrhage cases (through hemodilution using physiologic serum) and
      dehydration (through hemoconcentration by removing an aliquot of plasma after
      centrifugation), respectively. RESULTS: A total of 146 tests were performed on 52
      samples; 126 in the hemodilution group (42 for each native, diluted 1/2, and
      diluted 1/4 samples) and 20 in the hemoconcentration group (10 for each native
      and 10% concentrated samples). Hematocrit in the tested samples ranged from 9.8%
      to 57.6% while hemoglobin levels ranged from 3.2 to 20.1 g/dL. The phenotype
      profile detected with the MDmulticard using the simplified protocol resulted in
      22 A, seven B, 20 O, and three AB, of which nine were D- and five were Kell
      positive. No discrepancies were found with respect to the results obtained with
      the reference method. CONCLUSION: The simplified protocol for MDmulticard use
      could be considered a reliable method for blood typing in extreme environment or
      emergency situations, worsened by red blood cell dilution or concentration.

PMID- 29193134
TI  - Corrigendum.

PMID- 29193132
TI  - Robotic dentistry - will it replace dentists?

PMID- 29193135
TI  - Continuing Professional Development Quiz.

PMID- 29193136
TI  - Clinical indications for intravenous immunoglobulin utilization in a tertiary
      medical center: a 9-year retrospective study.
AB  - BACKGROUND: Intravenous immunoglobulins (IVIG) are a biologic product originally
      developed to treat immunocompromised patients. In the past decades, there has
      been increased utilization of IVIG in autoimmune conditions. The objectives were
      to evaluate the clinical use of IVIG in the largest tertiary medical center in
      Israel and to determine top uses, estimate off-label usage, and assess
      consumption of this blood product. STUDY DESIGN AND METHODS: We conducted an
      observational, retrospective study involving all patients who received IVIG from
      2007 through 2015. Subjects were classified into five groups according to the
      indication for treatment. RESULTS: A total of 1117 patients were identified. The
      mean (+/-SD) ages of adults and children were 55 +/- 17 and 8 +/- 7 years,
      respectively. Most common indication for treatment were immune-mediated
      conditions (54%), followed by secondary immunodeficiency (28%), primary
      immunodeficiency (10%), infections (4%), and miscellaneous (4%). The main immune
      mediated conditions treated were hematologic disorders (305 patients, 27%),
      neurologic disorders (219 patients, 20%), and rheumatologic conditions (79
      patients, 7%). Overall, a significant change in study period was observed in the
      number of patients (p < 0.001), consumption of IVIG (p < 0.01), and amount of
      IVIG administered per patient (p < 0.01). Fifty-six percent of the IVIG infusions
      were given for off-label Food and Drug Administration (FDA) indications.
      CONCLUSION: In this study, we demonstrated that immune-mediated conditions
      represent the majority of indications for treatment with IVIG. We observed a 417%
      increase in IVIG administration (g) over time, attributed mainly to autoimmune
      diseases. Many indications are still off-label according to FDA recommendations.

PMID- 29193137
TI  - Fatal toxoplasmosis in a southern muriqui (Brachyteles arachnoides) from Sao
      Paulo state, Brazil: Pathological, immunohistochemical, and molecular
      characterization.
AB  - We report the pathological, immunohistochemical, and molecular features of fatal
      acute systemic toxoplasmosis in an adult, female, free-living southern muriqui
      (Brachyteles arachnoides) from Sao Paulo state, Brazil. PCR-RFLP genotyping
      analysis identified the #21 genotype of Toxoplasma gondii. This represents the
      first report of acute toxoplasmosis involving this genotype in humans and
      animals.

PMID- 29193138
TI  - Intranasal immunization with phosphorylcholine suppresses allergic rhinitis in
      mice.
AB  - OBJECTIVES/HYPOTHESIS: Intranasal immunization with phosphorylcholine (PC) is
      known to reduce immunoglobulin (Ig)E production. However, its effects on the
      occurrence of allergic rhinitis (AR) are unknown. This study was performed to
      evaluate the effects of PC-keyhole limpet hemocyanin (PC-KLH) and to examine the
      effects on the occurrence of AR in a murine model of AR. STUDY DESIGN: In vivo
      study using an animal model. METHODS: Forty-five female BALB/c mice were divided
      into three groups; those pretreated with intranasal administration of PC-KLH
      followed by intraperitoneal sensitization and nasal challenge with ovalbumin
      (OVA) (group A), those untreated with PC-KLH followed by sensitization and nasal
      challenge with OVA (group B), and those untreated with PC-KLH or OVA as controls
      (group C). Nasal symptoms, allergic inflammation in the nasal mucosa, OVA
      specific IgE production, and cytokine profile were compared among those three
      groups. Dendritic cells (DCs) were isolated from splenic cells and PC-KLH
      stimulated interleukin (IL)-12p40 production was measured. RESULTS: The mice
      pretreated with PC-KLH showed lower allergic nasal symptoms and inflammation
      compared to untreated mice. The levels of total IgE and OVA-specific IgE in
      serum, and IL-4 production by nasal and splenic CD4+ T cells were significantly
      reduced by PC-KLH pretreatment. Furthermore, IL-12p40 production by DCs was
      induced by PC-KLH in a dose-dependent manner. CONCLUSIONS: Intranasal
      administration of PC-KLH suppressed allergic inflammation in nasal mucosa and
      antigen-specific IgE production by downregulating Th2-type immune response.
      Intranasal immunization with PC might be useful to prevent AR and upper airway
      bacterial infection. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E234-E240, 2018.

PMID- 29193140
TI  - Erratum.

PMID- 29193139
TI  - Early signs of cardiovascular dysregulation in young adult binge drinkers.
AB  - Binge drinking is widespread on American college campuses, but its effects on the
      cardiovascular system are poorly understood. This study sought evidence of
      preclinical cardiovascular changes in binge drinking young adults (n = 24)
      compared to nondrinking (n = 24) and social drinking (n = 23) peers during
      baseline, paced sighing (0.033 Hz), and paced breathing (0.1 Hz) tasks. Binge
      drinkers showed consistent but often statistically nonsignificant evidence of
      greater sympathetic activation and reduced baroreflex sensitivity. Interestingly,
      the structure of group-averaged baseline heart rate spectra was considerably
      different between groups in the low frequency range (0.05-0.15 Hz). In
      particular, the binge drinking group-averaged spectra showed several spectral
      peaks not evident in the other groups, possibly indicating two functionally
      distinct subranges (0.05-0.08 and 0.08-0.15 Hz) that reflect vascular tone
      baroreflex activity and heart rate baroreflex activity, respectively. Vascular
      tone baroreflex gain and power in two peaks in the 0.05-0.08 Hz range were
      associated with years of drinking in the binge drinking group. Vascular
      dysfunction may be an early indicator of drinking-related change in the
      cardiovascular system.

PMID- 29193141
TI  - Behavioral variability as avoidance behavior.
AB  - This study aimed to investigate whether variable patterns of responses can be
      acquired and maintained by negative reinforcement under an avoidance contingency.
      Six male Wistar rats were exposed to sessions in which behavioral variability was
      reinforced according to a Lag contingency: Sequences of three responses on two
      levers had to differ from one, two or three previous sequences for shocks to be
      avoided (Lag 1, Lag 2 and Lag 3, respectively). Performance under the Lag
      conditions was compared with performance on a Yoke condition in which the animals
      received the same reinforcement frequency and distribution as in the Lag
      condition but behavioral variability was not required. The results showed that
      most of the subjects varied their sequences under the Lag contingencies, avoiding
      shocks with relatively high probability (>= 0.7). Under the Yoke procedure,
      responding continued to occur with high probability, but the behavioral
      variability decreased. These results suggest that behavioral variability can be
      negatively reinforced.

PMID- 29193143
TI  - Anti-inflammatory and anti-apoptotic effects of the combination of Ligusticum
      chuanxiong and Radix Paeoniae against focal cerebral ischaemia via
      TLR4/MyD88/MAPK/NF-kappaB signalling pathway in MCAO rats.
AB  - OBJECTIVE: This study was performed to assess the anti-inflammatory and anti
      apoptotic effects of the combination of Ligusticum chuanxiong and Radix Paeoniae
      (XS) on focal cerebral ischaemic stroke. METHODS: MCAO rats were used to evaluate
      the effect of XS on stroke. Cerebral water content was measured, and the levels
      of IFN-gamma, IL-1beta, IL-6 and IL-12 in serum and brain were assessed by ELISA
      kits. Protein expressions including p-p38, p-38, TLR-4, p-ERK, ERK, TLR-5, NF
      kappaBp65, Myd88, Caspase-3 and Caspase-12 were examined by WB and IHC. Q-PCR was
      applied to examine IL-1beta and IL-6 mRNA levels in the rat brain of each group.
      KEY FINDINGS: XS treatment remarkedly decreased the levels of IFN-gamma, IL
      1beta, IL-6 and IL-12 in serum and brain tissues of MCAO rats. In the ischaemic
      brain, the expressions of TLR-4, TLR-5, p-p38, p-ERK, Myd88, NF-kappaBp65,
      Caspase-3 and Caspase-12 were increased significantly, while the treatment
      attenuated the activated expressions by MCAO. XS also downregulated Caspase-3 and
      Caspase-12 expressions. IL-1beta and IL-6 mRNA levels in MCAO brain tissue were
      decreased by XS treatment. CONCLUSIONS: XS could protect MCAO rats by anti
      inflammation and anti-apoptosis through TLR4/MyD88/MAPK/NF-kappaB signalling
      pathway. Furthermore, the combination has a more meaningful improvement on focal
      cerebral ischaemic stroke.

PMID- 29193144
TI  - Simulating thermal effects of MR-guided focused ultrasound in cortical bone and
      its surrounding tissue.
AB  - PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) is emerging as a
      treatment alternative for osteoid osteoma and painful bone metastases. This study
      describes a new simulation platform that predicts the distribution of heat
      generated by MRgFUS when applied to bone tissue. METHODS: Calculation of the
      temperature distribution was performed using two mathematical models. The first
      determined the propagation and absorption of acoustic energy through each medium,
      and this was performed using a multilayered approximation of the Rayleigh
      integral method. The ultrasound energy distribution derived from these equations
      could then be converted to heat energy, and the second mathematical model would
      then use the heat generated to determine the final temperature distribution using
      a finite-difference time-domain application of Pennes' bio-heat transfer
      equation. Anatomical surface geometry was generated using a modified version of a
      mesh-based semiautomatic segmentation algorithm, and both the acoustic and
      thermodynamic models were calculated using a parallelized algorithm running on a
      graphics processing unit (GPU) to greatly accelerate computation time. A series
      of seven porcine experiments were performed to validate the model, comparing
      simulated temperatures to MR thermometry and assessing spatial, temporal, and
      maximum temperature accuracy in the soft tissue. RESULTS: The parallelized
      algorithm performed acoustic and thermodynamic calculations on grids of over 108
      voxels in under 30 s for a simulated 20 s of heating and 40 s of cooling, with a
      maximum time per calculated voxel of less than 0.3 MUs. Accuracy was assessed by
      comparing the soft tissue thermometry to the simulation in the soft tissue
      adjacent to bone using four metrics. The maximum temperature difference between
      the simulation and thermometry in a region of interest around the bone was
      measured to be 5.43 +/- 3.51 degrees C average absolute difference and a
      percentage difference of 16.7%. The difference in heating location resulted in a
      total root-mean-square error of 4.21 +/- 1.43 mm. The total size of the ablated
      tissue calculated from the thermal dose approximation in the simulation was, on
      average, 67.6% smaller than measured from the thermometry. The cooldown was much
      faster in the simulation, where it decreased by 14.22 +/- 4.10 degrees C more
      than the thermometry in 40 s after sonication ended. CONCLUSIONS: The use of a
      Rayleigh-based acoustic model combined with a discretized bio-heat transfer model
      provided a rapid three-dimensional calculation of the temperature distribution
      through bone and soft tissue during MRgFUS application, and the parallelized GPU
      algorithm provided the computational speed that would be necessary for an
      intraoperative treatment planning software platform.

PMID- 29193145
TI  - Polyethylene glycol as marker for nitrofurazone allergy: 20 years of experience
      from Turkey.
AB  - BACKGROUND: Polyethylene glycols (PEGs) and propylene glycol (PG) are used as
      vehicles in various medicinal and cosmetic products. They are potential contact
      sensitizers, including low molecular weight PEGs in nitrofurazone preparations
      that are still widely used in Turkey. OBJECTIVES: To investigate the prevalence
      of allergic contact dermatitis caused by PEG and PG in a relatively large group
      of patients in Turkey. METHODS: In this retrospective, cross-sectional, single
      centre study, 836 patients patch tested with PEG and PG between 1996 and 2015
      were reviewed. RESULTS: Thirty-five patients (4.2%) showed positive patch test
      reactions to PEG, and 7 (0.8%) showed positive patch test reactions to PG, partly
      as late positive reactions with PEG. PEG sensitivity was almost exclusively
      related to nitrofurazone allergy. Patch test reactions to PG were currently
      relevant mainly with regard to the use of minoxidil, and antiherpetic or
      corticosteroid creams. Ten patients (25%) had concomitant contact allergies to
      various topical drugs containing mainly PEGs. CONCLUSIONS: PEG sensitivity seems
      to be a marker for contact allergy to topical nitrofurazone in Turkey.
      Nitrofurazone allergy appears to favour concomitant sensitization to PEG. We
      would suggest the inclusion of PEG in an extended baseline patch test series in
      Turkey. Late patch test readings are important to diagnose delayed positive
      reactions to PEG.

PMID- 29193147
TI  - Physiological evidence that Piscirickettsia salmonis produces siderophores and
      uses iron from different sources.

PMID- 29193148
TI  - Multi-gene phylogeny of jacks and pompanos (Carangidae), including placement of
      monotypic vadigo Campogramma glaycos.
AB  - In this study, the phylogenetic trees of jacks and pompanos (Carangidae), an
      ecologically and morphologically diverse, globally distributed fish family, are
      inferred from a complete, concatenated data set of two mitochondrial (cytochrome
      c oxidase I, cytochrome b) loci and one nuclear (myosin heavy chain 6) locus.
      Maximum likelihood and Bayesian inferences are largely congruent and show a clear
      separation of Carangidae into the four subfamilies: Scomberoidinae,
      Trachinotinae, Naucratinae and Caranginae. The inclusion of the carangid sister
      lineages Coryphaenidae (dolphinfishes) and Rachycentridae (cobia), however,
      render Carangidae paraphyletic. The phylogenetic trees also show with high
      statistical support that the monotypic vadigo Campogramma glaycos is the sister
      to all other species within the Naucratinae.

PMID- 29193146
TI  - Control networks and hubs.
AB  - Executive control functions are associated with frontal, parietal, cingulate, and
      insular brain regions that interact through distributed large-scale networks.
      Here, we discuss how fMRI functional connectivity can shed light on the
      organization of control networks and how they interact with other parts of the
      brain. In the first section of our review, we present convergent evidence from
      fMRI functional connectivity, activation, and lesion studies that there are
      multiple dissociable control networks in the brain with distinct functional
      properties. In the second section, we discuss how graph theoretical concepts can
      help illuminate the mechanisms by which control networks interact with other
      brain regions to carry out goal-directed functions, focusing on the role of
      specialized hub regions for mediating cross-network interactions. Again, we use a
      combination of functional connectivity, lesion, and task activation studies to
      bolster this claim. We conclude that a large-scale network perspective provides
      important neurobiological constraints on the neural underpinnings of executive
      control, which will guide future basic and translational research into executive
      function and its disruption in disease.

PMID- 29193149
TI  - Case study: Scoliosis in a Bonobo (Pan paniscus).
AB  - Differential diagnosis of observed morphological features on an adult male bonobo
      skeleton was consistent with idiopathic scoliosis. Directional asymmetry was an
      order of magnitude higher compared with asymptomatic skeletons. This possible
      case of idiopathic scoliosis contributes to data that suggest a weaker tie
      between bipedalism and scoliosis than previously hypothesized.

PMID- 29193151
TI  - Refractory myasthenia gravis exacerbation triggered By pembrolizumab.

PMID- 29193150
TI  - Exposure to Alcohol Content in Movies and Initiation of Early Drinking
      Milestones.
AB  - BACKGROUND: Exposure to alcohol content in movies has been shown to be associated
      with adolescent use of alcohol, including earlier onset. This study examined the
      influence of movie alcohol exposure on subsequent alcohol onset, considering the
      social context (whether the movie was viewed with a friend or parent). We
      examined whether media's influence holds across a spectrum of early drinking
      milestones: sipping (but not consuming a full drink of) alcohol, consuming a full
      drink of alcohol, and engaging in heavy episodic drinking (HED). METHODS: Data
      were taken from a sample of 882 middle school youth (52% female; 24% non-White)
      enrolled in an ongoing study on alcohol initiation and progression. Exposure to
      alcohol content in films was measured using a method that combines content
      analysis and random assignment of movie titles to youth surveys. The hazard of
      initiating alcohol use (sip, full drink, HED) as a function of exposure was
      estimated using survival analysis. Associations were adjusted for demographic,
      personality, and social influence factors known to be associated with both movie
      exposure and alcohol use. RESULTS: Exposure to alcohol content was common. Hours
      of exposure prospectively predicted earlier onset of alcohol involvement across
      all outcomes. Viewing movies with friends appeared to augment the media exposure
      effect, in contrast to viewing movies with parents, which was not a significant
      predictor of initiation. CONCLUSIONS: Exposure to alcohol in films is involved in
      the entry into early stages of alcohol involvement. Findings support further
      investigation into the role of the media in underage drinking, especially in the
      context of consuming media with friends and peers. Limiting media exposure and/or
      stronger Federal Trade Commission oversight of movie ratings should be a priority
      for preventing underage drinking.

PMID- 29193152
TI  - The high prevalence of pathogenic Vibrio harveyi with multiple antibiotic
      resistance in scale drop and muscle necrosis disease of the hybrid grouper,
      Epinephelus fuscoguttatus (?) * E. lanceolatus (?), in China.
AB  - Scale drop and muscle necrosis disease with high mortality widely occurred
      recently in the hybrid grouper (Epinephelus fuscoguttatus ? * E. lanceolatus ?),
      a crucial cultured marine fish species in China. In this study, 30 Harveyi clade
      isolates of 27 Vibrio harveyi strains were isolated from diseased hybrid groupers
      in the south-east and north-east coastal areas of China. A total of 22 V. harveyi
      strains were determined to be pathogenic, and most challenged fish died within 2
      days of infection; surviving individuals exhibited scale drop and deep dermal
      lesions as naturally diseased fish. Although five typical virulence genes,
      including luxR, toxRVh , chiA, serine protease and vhh widely existed in V.
      harveyi, no obvious correlation was established between virulent strains and
      virulence genes harboured in them. Furthermore, multiple antibiotic resistance
      was widely exhibited in Harveyi clade strains, particularly for penicillins,
      polypeptides, lincomycins, acetylspiramycin, streptomycin, metronidazole and
      bacitracin. And the multiple antibiotic resistance indices were gradually
      decreased from southern to northern areas of China. This study demonstrated that
      the pathogenic V. harveyi with multiple antibiotic resistance is highly prevalent
      in hybrid grouper in China, which requires particular attention.

PMID- 29193153
TI  - Aquaporin 4 expression in human skeletal muscle fiber types.
AB  - INTRODUCTION: Aquaporins (AQPs) are a family of transmembrane proteins involved
      in the maintenance of osmotic gradients. AQP4 is abundant in skeletal muscle,
      where it seems to be associated with glycolytic metabolism. We investigated the
      pattern of expression of AQP4 in normal human myofibers relative to the main
      forms of myosin heavy chain (MHC). METHODS: Six normal human muscle biopsies were
      analyzed by double immunofluorescence for co-expression of AQP4 and slow or fast
      MHC. RESULTS: A high percentage (64-99%) of MHC-fast positive fibers showed
      immunoreaction for AQP4. Immunoreactivity for AQP4 was also present in MHC-slow
      positive fibers, but with a higher variability (5-72%) among biopsies.
      DISCUSSION: The expression pattern of AQP4 in human myofibers is highly variable
      among different patients and cannot be predicted for single fibers depending on
      MHC type expression. Other factors, possibly related to muscle activity, may
      modulate AQP4 expression. Muscle Nerve 57: 856-859, 2018.

PMID- 29193154
TI  - Prevalence and predictors of peripheral neuropathy in nondiabetic children with
      chronic kidney disease.
AB  - INTRODUCTION: This study sought to determine the prevalence and predictors of
      peripheral neuropathy in nondiabetic children with chronic kidney disease (CKD).
      METHODS: Fifty-one consecutive normally nourished children, 3-18 years of age,
      with CKD stages IV and V of nondiabetic etiology were enrolled from May to
      December 2012. Nerve conduction studies were performed in 50 children. Blood
      samples were analyzed for the biochemical parameters, trace elements, and
      micronutrients. RESULTS: The prevalence of peripheral neuropathy in our cohort
      was 52% (95% confidence interval 37.65, 66.34). The majority (80.8%) of the
      children had axonal neuropathy, and 11.5% had demyelinating neuropathy. Isolated
      motor neuropathy was identified in 92.3% of the children, and sensorimotor
      neuropathy was identified in 7.6%. The significant risk factors associated with
      peripheral neuropathy were older age, low serum copper, and dialysis therapy.
      DISCUSSION: Electrodiagnostic studies should be performed in children with CKD to
      assess for peripheral neuropathy for the purpose of optimizing medical care.
      Muscle Nerve 57: 792-798, 2018.

PMID- 29193155
TI  - Electrodiagnostic misdiagnosis of chronic inflammatory demyelinating
      polyneuropathy: What are the problems? and how to right the wrongs.

PMID- 29193156
TI  - Validating and implementing the use of an infusion pump for the administration of
      thawed hematopoietic progenitor cells-a single-institution experience.
AB  - BACKGROUND: Direct thaw and administration of previously cryopreserved peripheral
      blood stem cell products is a commonly used practice and should be performed
      rapidly to reduce cellular damage caused by dimethyl sulfoxide exposure. Cells
      are typically thawed at the bedside and infused by gravity through a high-flow
      rate central venous catheter. An existing nontunneled catheter is occasionally
      used instead and often results in a slower infusion rate. To ensure expedient and
      consistent infusions, we validated and implemented the use of an infusion pump
      for thawed peripheral blood stem cells. STUDY DESIGN AND METHODS: Validation was
      performed in two phases: in vitro simulation and in vivo clinical assessment.
      Total nucleated cell recovery and viability plus progenitor cell viability and
      potency were compared in vitro between two cryopreserved peripheral blood stem
      cell units that were either passed through a preset infusion pump or drained by
      gravity. The infusion rate, adverse events, and engraftment times were
      retrospectively compared between patients who received infusions by infusion pump
      (n = 35) and by gravity (n = 38). RESULTS: No significant differences were
      observed in vitro between the infusion methods for all measured variables.
      Overall infusion rates were similar in vivo for both groups but were
      significantly lower for patients who had nontunneled catheters that delivered the
      infusion by gravity. The time to neutrophil and platelet engraftment was similar
      for both groups. CONCLUSION: This is the first study to assess the use of an
      infusion pump for stem cell transplant. The use of an infusion pump for
      peripheral blood stem cell infusion is safe, provides a reliable and consistent
      infusion method, and can mitigate the effect of the type of venous access line
      used.

PMID- 29193157
TI  - Aeromonas caviae inhibits hepatic enzymes of the phosphotransfer network in
      experimentally infected silver catfish: Impairment on bioenergetics.
AB  - Several studies have been demonstrated that phosphotransfer network, through the
      adenylate kinase (AK) and pyruvate kinase (PK) activities, allows for new
      perspectives leading to understanding of disease conditions associated with
      disturbances in energy metabolism, metabolic monitoring and signalling. In this
      sense, the aim of this study was to evaluate whether experimental infection by
      Aeromonas caviae alters hepatic AK and PK activities of silver catfish Rhamdia
      quelen. Hepatic AK and PK activities decreased in infected animals compared to
      uninfected animals, as well as the hepatic adenosine triphosphate (ATP) levels.
      Also, a severe hepatic damage was observed in the infected animals due to the
      presence of dilation and congestion of vessels, degeneration of hepatocytes and
      loss of liver parenchyma architecture and sinusoidal structure. Therefore, we
      have demonstrated, for the first time, that experimental infection by A. caviae
      inhibits key enzymes linked to the communication between sites of ATP generation
      and ATP utilization. Moreover, the absence of a reciprocal compensatory mechanism
      between these enzymes contributes directly to hepatic damage and for a severe
      energetic imbalance, which may contribute to disease pathophysiology.

PMID- 29193158
TI  - Terlipressin-induced modifications of Doppler ultrasound signals of systemic
      arteries in preterm infants with vasoactive-resistant patent ductus arteriosus: A
      pilot study.
AB  - PURPOSE: To study the effects of terlipressin (TP) infusion on systemic
      perfusion, estimated with pulsed-wave Doppler ultrasonography of systemic
      arteries, in a population of extremely low birth-weight (ELBW) preterm infants
      with vasoactive-resistant ductus arteriosus. METHODS: This prospective,
      observational cohort included, during five years, 12 ELBW infants with
      hemodynamically significant patent ductus arteriosus and absent or reversed
      diastolic flow at Doppler ultrasonography of systemic arteries, despite treatment
      and high-dose vasoactive support. We measured flow velocity of the anterior
      cerebral, right renal, and superior mesenteric arteries before and after TP
      infusion. Changes were evaluated by Spearman's rho coefficient analysis, Wilcoxon
      signed-rank, and Friedman test. RESULTS: Time-averaged mean velocity of the renal
      artery (P = .028) increased, while renal pulsatility (P = .010) and resistance (P
      = .004) indexes, and cerebral artery resistance index (P = .021) decreased after
      TP infusion. Time-averaged mean velocity of the anterior cerebral artery
      proportionately increased with dopamine dose (rho = 0.678; P = .015), but showed
      opposite shifts after TP (rho = -0.662; P = .024). CONCLUSIONS: These changes
      suggest that TP may improve systemic perfusion in the ELBW infants with
      vasoactive-resistant ductus arteriosus.

PMID- 29193159
TI  - Investigation of the quality of stored red blood cells after simulated air drop
      in the maritime environment.
AB  - BACKGROUND: Maritime medical capability may be compromised by blood resupply. Air
      dropped red blood cells (RBCs) is a possible mitigation factor. This study set
      out to evaluate RBC storage variables after a simulated parachute air drop into
      the sea, as limited data exist. STUDY DESIGN AND METHODS: The air load
      construction for the air drop of blood was subject to static drop assessment to
      simulate a worst-case parachute drop scenario. One control and two test Golden
      Hour shipping containers were each packaged with 10 RBC units. The control box
      was not dropped; Test Boxes 1 and 2 were further reinforced with waterproof boxes
      and underwent a simulated air drop on Day 7 or Day 8 postdonation, respectively.
      One day after the drop and once a week thereafter until Day 43 of storage, RBCs
      from each box were sampled and tested for full blood counts, hemolysis, adenosine
      triphosphate, 2,3-diphosphoglycerate, pH, extracellular potassium, glucose,
      lactate, deformability, and RBC microvesicles. RESULTS: The packaging
      configuration completed the air drop with no water ingress or physical damage.
      All units met UK specifications for volume, hemoglobin, and hemolysis. There were
      no significant differences for any of the variables studied between RBCs in the
      control box compared to RBCs in Test Boxes 1 and 2 combined over storage.
      CONCLUSION: The test proved that the packaging solution and the impact of a
      maritime air drop as performed in this study, on Day 7 or Day 8 postdonation, did
      not affect the in vitro quality of RBCs in SAGM over storage for 35 days.

PMID- 29193161
TI  - Chlorhexidine.

PMID- 29193160
TI  - Multicenter Experience With Mechanical Circulatory Support Using a New Diagonal
      Pump in 233 Children.
AB  - Technological innovations in pediatric extracorporeal life support circuits can
      reduce system-related complications and may improve patients' outcome. The
      Deltastream DP3 (Medos Medizintechnik AG, Stolberg, Germany) is a novel
      rotational pump with a diagonally streamed impeller that can be used over a broad
      range of flows. We collected patient data from seven pediatric centers to conduct
      a retrospective cohort study. We examined 233 patients whose median age was 1.9
      (0-201) months. The DP3 system was used for cardiopulmonary support as veno
      arterial extracorporeal membrane oxygenation (ECMO) in 162 patients. Respiratory
      support via veno-venous ECMO was provided in 63 patients. The pump was used as a
      ventricular assist device in eight patients. Median supporting time was 5.5 (0.2
      69) days and the weaning rate was 72.5%. The discharge home rate was 62% in the
      pulmonary group versus 55% in the cardiac group. Extracorporeal cardiopulmonary
      resuscitation was carried out in 24 patients (10%) with a survival to discharge
      of rate of 37.5%. About 106 (47%) children experienced no complications, while
      33% suffered bleeding requiring blood transfusion or surgical intervention. Three
      patients suffered a fatal cerebral event. Renal replacement therapy was performed
      in 28% and pump or oxygenator exchange in 26%. Multivariable analysis identified
      system exchange (OR 1.94), kidney failure (OR 3.43), and complications on support
      (OR 2.56) as risk factors for dismal outcome. This novel diagonal pump has
      demonstrated its efficacy in all kinds of mechanical circulatory and respiratory
      support, revealing good survival rates.

PMID- 29193162
TI  - Influence of fertilizers and rice cultivation methods on the abundance and
      diversity of phyllosphere microbiome.
AB  - Rice paddies are man-made, cross-over ecologies of aquatic and terrestrial
      systems, which favor the proliferation of characteristic microbial communities.
      Moisture regimes under flooded and different levels of irrigation such as in
      direct seeded rice (DSR) and system of rice intensification (SRI) lead to
      modulation in crop physiology, soil nutrient availability, and the soil
      microbiome. However, the diversity of the rice phyllosphere microbiome is less
      investigated in terms of the influence of fertilizer application and the method
      of rice cultivation (conventional-flooded, DSR and SRI). Scanning electron
      micrographs revealed the presence of bacteria as aggregates at microsites of the
      leaves. Phylogenetic analysis of the dominant culturable bacterial isolates using
      16S rDNA sequences revealed that they belonged to the genera - Bacillus,
      Brevibacillus, Pantoea, Enterobacter, Pseudomonas, Erwinia, and Streptomyces.
      Fertilizer application brought about a distinct modulation in the communities
      belonging to phyla such as Bacteriodetes, Firmicutes, and Planctomyces, besides
      Proteobacteria. The cyanobacterial population was much influenced by the
      cultivation methods, particularly the SRI. Principal component analysis (PCA),
      involving the culturable phyllospheric microbial groups and leaf attributes
      (nutrients and pigments), illustrated the importance of leaf nitrogen and zinc.
      Also, the communities of the phylum Firmicutes exhibited marked changes in terms
      of the diversity, not only due to the cultivation method, but also the
      application of fertilizers. Thus, the cultivation methods and fertilizer
      application played important roles in modulating both the structural
      (taxonomical) and functional attributes of the phyllosphere microbiome.

PMID- 29193164
TI  - Clinical and Supervisory Considerations for Transgender Therapists: Implications
      for Working with Clients.
AB  - Transgender therapists have unique and valuable perspectives into how gender
      organizes the therapeutic process. Currently, in the MFT field, there is
      discussion of the cisgender therapist's experience in the therapy room, but no
      known articles on the transgender therapist's experience. This article provides
      insight into the experiences of transgender therapists around issues of self
      disclosure, social locations of both therapist and client, and clinical
      supervision. Drawing from our clinical experiences as transmen, we highlight
      special considerations for working with cisgender, queer, and transgender
      clients. Implications for supervision of transgender therapists are also
      discussed. As more gender diverse students seek MFT training, there is an urgent
      need to acknowledge their perspectives. This article is a call for beginning
      conversations in this direction.

PMID- 29193163
TI  - Production, purification, and characterization of a novel serine-esterase from
      Aspergillus westerdijkiae.
AB  - Esterases hydrolyze water soluble short chain fatty acids esters and are
      biotechnologically important. A strain of Aspergillus westerdijkiae isolated from
      cooking oil for recycling was found to secrete an esterase. The best enzyme
      production (19-24 U/ml of filtrate) culture conditions were stablished. The
      protein was purified using ammonium sulphate precipitation, dialysis, and a
      chromatographic step in Sephacryl S-200 HR. The 32 kDa purified protein presented
      an optimal temperature of 40 degrees C, with a T50 of 48.95 degrees C, and an
      optimal pH of 8.0. KM and Vmax were 638.11 uM for p-NPB and 5.47 umol of released
      p-NP . min-1  . ug-1 of protein, respectively. The purified enzyme was partially
      active in the presence of 25% acetone. PMSF inhibited the enzyme, indicating that
      it is a serine hydrolase. MS enzyme peptides sequences were used to find the
      protein in the A. westerdijkiae sequenced genome. A structure model demonstrated
      that the protein is a member of the a/beta -hydrolase fold superfamily.

PMID- 29193165
TI  - Precise Quantitative Assessment of the Clinical Performances of Two High-Flux
      Polysulfone Hemodialyzers in Hemodialysis: Validation of a Blood-Based Simple
      Kinetic Model Versus Direct Dialysis Quantification.
AB  - Highly permeable dialysis membranes with better design filters have contributed
      to improved solute removal and dialysis efficacy. However, solute membrane
      permeability needs to be well controlled to avoid increased loss of albumin that
      is considered to be detrimental for dialysis patients. A novel high-flux dialyzer
      type (FX CorDiax; Fresenius Medical Care) incorporating an advanced polysulfone
      membrane modified with nano-controlled spinning technology to enhance the
      elimination of a broader spectrum of uremic toxins has been released. The aim of
      this study was to compare in the clinical setting two dialyzer types having the
      same surface area, the current (FX dialyzer) and the new dialyzer generation (FX
      CorDiax), with respect to solute removal capacity over a broad spectrum of
      markers, including assessment of albumin loss based on a direct dialysis
      quantification method. We performed a crossover study following an A1-B-A2 design
      involving 10 patients. Phase A1 was 1 week of thrice-weekly bicarbonate
      hemodialysis with the FX dialyzer, 4 h per treatment; phase B was performed with
      a similar treatment regimen but with a new FX CorDiax dialyzer and finally the
      phase A2 was repeated with FX dialyzer as the former phase. Solute removal
      markers of interest were assessed from blood samples taken before and after
      treatment and from total spent dialysate collection (direct dialysis
      quantification) permitting a mass transfer calculation (mg/session into total
      spent dialysate/ultrafiltrate). On the blood side, there were no significant
      differences in the solute percent reduction between FX CorDiax 80 and FX 80. On
      the dialysate side, no difference was observed regarding eliminated mass of
      different solutes including beta2 -microglobulin (143.1 +/- 33.6 vs. 138.3 +/-
      41.9 mg, P = 0.8), while the solute mass removal of total protein (1.65 +/- 0.51
      vs. 2.14 +/- 0.75 g, P = 0.04), and albumin (0.41 +/- 0.21 vs. 1.22 +/- 0.51 g, P
      < 0.001) were significantly less for FX CorDiax 80 compared to the FX 80
      dialyzer. The results of this cross-over study indicate that the new FX CorDiax
      dialyzer has highly effective removal of middle molecules, without any
      concomitant increase in total protein and albumin loss. The clinical relevance
      and potential benefit of this finding needs to be determined.

PMID- 29193166
TI  - Multiplex identification of sepsis-causing Gram-negative pathogens from the
      plasma of infected blood.
AB  - Early and accurate detection of bacterial pathogens in the blood is the most
      crucial step for sepsis management. Gram-negative bacteria are the most common
      organisms causing severe sepsis and responsible for high morbidity and mortality.
      We aimed to develop a method for rapid multiplex identification of clinically
      important Gram-negative pathogens and also validated whether our system can
      identify Gram-negative pathogens with the cell-free plasm DNA from infected
      blood. We designed five MLPA probe sets targeting the genes specific to major
      Gram-negative pathogens (uidA and lacY for E. coli, ompA for A. baumannii, phoE
      for K. pneumoniae, and ecfX for P. aeruginosa) and one set targeting the CTX-M
      group 1 to identify the ESBL producing Gram-negative pathogens. All six target
      specific peaks were clearly separated without any non-specific peaks in a
      multiplex reaction condition. The minimum detection limit was 100 fg of pathogen
      DNA. When we tested 28 Gram-negative clinical isolates, all of them were
      successfully identified without any non-specific peaks. To evaluate the clinical
      applicability, we tested seven blood samples from febrile patients. Three blood
      culture positive cases showed E. coli specific peaks, while no peak was detected
      in the other four culture negative samples. This technology can be useful for
      detection of major sepsis-causing, drug-resistant Gram-negative pathogens and
      also the major ESBL producing Gram-negatives from the blood of sepsis patients in
      a clinical setting. This system can help early initiation of effective
      antimicrobial treatment against Gram-negative pathogens for sepsis patients,
      which is very crucial for better treatment outcomes.

PMID- 29193167
TI  - Childbearing importance: A qualitative study of women with infertility in China.
AB  - The primary goal of this study was to examine and describe the importance of
      childbearing as perceived by infertile women in the Chinese familial and social
      context. We adopted a qualitative descriptive method and conducted semi
      structured interviews with female patients diagnosed with infertility.
      Participants were recruited at a high-volume fertility clinic in Tianjin, China.
      Fifteen women with a diagnosis of infertility were interviewed for 60-90 min.
      Data were analyzed by thematic analysis. Two themes supported the importance of
      childbearing for Chinese women with infertility: childbearing as natural law, and
      childbearing for relational harmony. Childbearing as natural law referred to
      intrinsic forces to seek a child, including (i) achieving motherhood and
      womanhood and (ii) experiencing a developmental transition with childbearing as a
      landmark. Relational harmony included three primary factors: (i) to maintain
      marital quality by preventing marital failure and rejuvenating an unsatisfactory
      marital relationship; (ii) to fulfill both authoritative and reciprocal filial
      piety; (iii) to build a sense of normalcy within family and social networks. In
      summary, infertility resulted in loss of motherhood, womanhood, and a smooth
      developmental transition. Moreover, it threatened relationship harmony in the
      marriage, family, and social life. These insights on the value of childbearing in
      the Chinese context can inform healthcare professionals in identify infertility
      related demands and developing relevant psychosocial services for people with
      infertility.

PMID- 29193168
TI  - Energy response corrections for profile measurements using a combination of
      different detector types.
AB  - PURPOSE: Different detector properties will heavily affect the results of off
      axis measurements outside of radiation fields, where a different energy spectrum
      is encountered. While a diode detector would show a high spatial resolution, it
      contains high atomic number elements, which lead to perturbations and energy
      dependent response. An ionization chamber, on the other hand, has a much smaller
      energy dependence, but shows dose averaging over its larger active volume. We
      suggest a way to obtain spatial energy response corrections of a detector
      independent of its volume effect for profiles of arbitrary fields by using a
      combination of two detectors. METHODS: Measurements were performed at an Elekta
      Versa HD accelerator equipped with an Agility MLC. Dose profiles of fields
      between 10 * 4 cm2 and 0.6 * 0.6 cm2 were recorded several times, first with
      different small-field detectors (unshielded diode 60012 and stereotactic field
      detector SFD, microDiamond, EDGE, and PinPoint 31006) and then with a larger
      volume ionization chamber Semiflex 31010 for different photon beam qualities of
      6, 10, and 18 MV. Correction factors for the small-field detectors were obtained
      from the readings of the respective detector and the ionization chamber using a
      convolution method. Selected profiles were also recorded on film to enable a
      comparison. RESULTS: After applying the correction factors to the profiles
      measured with different detectors, agreement between the detectors and with
      profiles measured on EBT3 film was improved considerably. Differences in the full
      width half maximum obtained with the detectors and the film typically decreased
      by a factor of two. Off-axis correction factors outside of a 10 * 1 cm2 field
      ranged from about 1.3 for the EDGE diode about 10 mm from the field edge to 0.7
      for the PinPoint 31006 25 mm from the field edge. The microDiamond required
      corrections comparable in size to the Si-diodes and even exceeded the values in
      the tail region of the field. The SFD was found to require the smallest
      correction. The corrections typically became larger for higher energies and for
      smaller field sizes. CONCLUSIONS: With a combination of two detectors,
      experimentally derived correction factors can be obtained. Application of those
      factors leads to improved agreement between the measured profiles and those
      recorded on EBT3 film. The results also complement so far only Monte Carlo
      simulated values for the off-axis response of different detectors.

PMID- 29193169
TI  - Electronic remote blood issue combined with a computer-controlled, automated
      refrigerator for major surgery in operating theatres at a distance from the
      transfusion service.
AB  - BACKGROUND: The difficulty of supplying red blood cells within an adequate time
      to patients undergoing surgery is a known problem for transfusion services,
      particularly if the operating theater is located at some distance from the blood
      bank. The consequences frequently are that more blood is ordered than required;
      several units are allocated and issued; and unused units must be returned to the
      blood bank. Some sparse reports have demonstrated that remote blood issue systems
      can improve the efficiency of issuing blood. STUDY DESIGN AND METHODS: This study
      describes a computer-controlled, self-service, remote blood-release system,
      combined with an automated refrigerator, installed in a hospital at which major
      surgery was performed, located 5 kilometers away from the transfusion service.
      With this system, red blood cell units were electronically allocated to patients
      immediately before release, when the units actually were needed. Two 2-year
      periods, before and after implementation of the system, were compared. RESULTS:
      After implementation of the system, the ratio of red blood cell units returned to
      the transfusion service was reduced from 48.9% to 1.6% of the issued units (8852
      of 18,090 vs. 182 of 11,152 units; p < 0.0001), and the issue-to-transfusion
      ratio was reduced from 1.96 to 1.02. An increase in the number of transfused red
      blood cell units was observed, probably mainly due to changes in the number and
      complexity of surgical procedures. No transfusion errors occurred in the two
      periods. CONCLUSION: The current results demonstrate that the remote blood
      release system is safe and useful for improving the efficiency of blood issue for
      patients in remote operating theatres.

PMID- 29193170
TI  - Dielectrophoretic choking phenomenon of a deformable particle in a converging
      diverging microchannel.
AB  - The translational motion of small particles in an electrokinetic fluid flow
      through a constriction can be enhanced by an increase of the applied electric
      potential. Beyond a critical potential, however, the negative dielectrophoresis
      (DEP) can overpower other forces to prevent particles that are even smaller than
      the constriction from passing through the constriction. This DEP choking
      phenomenon was studied previously for rigid particles. Here, the DEP choking
      phenomenon is revisited for deformable particles, which are ubiquitous in many
      biomedical applications. Particle deformability is measured by the particle shear
      modulus, and the choking conditions are reported through a parametric study that
      includes the channel geometry, external electric potential, and particle zeta
      potential. The study was carried out using a numerical model based on an
      arbitrary Lagrangian-Eulerican (ALE) finite-element method.

PMID- 29193171
TI  - Into the theory of the partial-filling affinity capillary electrophoresis and the
      determination of apparent stability constants of analyte-ligand complexes.
AB  - The partial-filling affinity capillary electrophoresis (pf-ACE) works with a
      ligand present in a background electrolyte that forms a weak complex with an
      analyte. In contrast to a more popular mobility-shift affinity capillary
      electrophoresis, only a short plug of the ligand is introduced into a capillary
      in the pf-ACE. Both methods can serve for determining apparent stability
      constants of the formed complexes but this task is hindered in the pf-ACE by the
      fact that the analyte spends only a part of its migration time in a contact with
      the ligand. In 1998, Amini and Westerlund published a linearization strategy that
      allows for extracting an effective mobility of an analyte in the presence of a
      neutral ligand out of the pf-ACE data. The main purpose of this paper is to show
      that the original formula is only approximate. We derive a new formula and
      demonstrate its applicability by means of computer simulations. We further
      inspect several strategies of data processing in the pf-ACE regarding a risk of
      an error propagation. This establishes a good practice of determining apparent
      stability constants of analyte-ligand complexes by means of the pf-ACE.

PMID- 29193172
TI  - Smartphone-based colorimetric chiral recognition of ibuprofen using aptamers
      capped gold nanoparticles.
AB  - Sensitive and fast detection of ibuprofen enantiomers is very critical for
      required routine monitoring and risk assessment of trace pollutants in water
      samples. Here a simple, rapid and highly sensitive android smartphone application
      for chiral recognition was developed. Aptamer-capped gold nanoparticles (AuNPs)
      was demonstrated as an efficient detection platform for (S)-(+)-ibuprofen (S-Ibu)
      and (R)-(-)-ibuprofen (R-Ibu). Detachment of an enantioselective aptamer from the
      AuNPs surface and binding with an enantiomer of Ibu lead to AuNPs aggregation,
      which allows a rapid enantiodiscrimination of Ibu by monitoring the absorbance
      changes of AuNPs solution in the UV-vis spectrum. Under optimal conditions, the
      limit of detection for S-Ibu and R-Ibu was 1.24 and 3.91 pg/mL, respectively.
      These probes showed good chiral recognition ability in mixed samples (i.e. S-Ibu
      + R-Ibu) and environmental samples. These advantages can be further developed by
      quantitative measurement with smartphone, which opens new opportunities for on
      site detection of trace chiral pollutants in a simple and practical manner.

PMID- 29193173
TI  - The fractional laser-induced coagulation zone characterized over time by laser
      scanning confocal microscopy-A proof of concept study.
AB  - BACKGROUND: Ablative fractional laser (AFXL) is an acknowledged technique to
      increase uptake of topical agents in skin. Micro thermal ablation zones (MAZs)
      consist of ablated vertical channels surrounded by a coagulation zone (CZ). Laser
      scanning confocal microscopy (LSCM) images individual MAZs at 733 nm (reflectance
      confocal microscopy (RCM)). Further, LSCM can image sodium fluorescein (NaF)
      fluorescence with 488 nm excitation (fluorescence confocal microcopy (FCM)), a
      small hydrophilic test molecule (370 MW, log P -1.52), which may simulate uptake,
      bio-distribution and kinetics of small hydrophilic drugs. OBJECTIVES: To explore
      LSCM for combined investigations of CZ thickness and uptake, bio-distribution and
      kinetics of NaF in AFXL-exposed skin. STUDY DESIGNS/METHODS AND MATERIALS:
      Excised human abdominal skin samples were exposed to AFXL (15 mJ/microbeam, 2%
      density) and NaF gel (1000 MUg/ml, 10 MUl/cm2) in six repetitions, including
      untreated control samples. CZ thickness and spatiotemporal fluorescence
      intensities (FI) were quantified up to four hours after NaF application by RCM
      and FCM. Test sites were scanned to a depth of 200 MUm, quantifying thickness of
      skin compartments (stratum corneum, epidermis, upper dermis), individual CZ
      thicknesses and FI in CZ and surrounding skin. RESULTS: RCM images established
      skin morphology to a depth of 200 MUm. The CZ thickness measurements were
      feasible to a depth of 50 MUm, and remained unchanged over time at 50 MUm (P >
      0.5). FI were detected to a depth of 160 MUm and remained constant in CZ up to
      four hours after NaF application (15 minutes: 79 AU (73-92 AU), 60 minutes: 72 AU
      (58-82 AU), four hours: 78 AU (71-90 AU), P > 0.1). In surrounding skin, FI
      increased significantly over time, but remained lower than FI in CZ (15 minutes:
      21 AU (17-22 AU), 60 minutes: 21 AU (19-26 AU), four hours: 42 (31- 48 AU), P =
      0.03). AFXL-processed skin generated higher FI compared to non-laser processed
      skin in epidermis and upper dermis at 60 minutes and four hours (P = 0.03).
      CONCLUSIONS: By LSCM, assessment of the AFXL-induced CZ thickness was feasible to
      a depth of 50 MUm, and assessment of FI from a small hydrophilic test molecule,
      NaF in CZ and surrounding skin feasible to a depth of 160 MUm. Lasers Surg. Med.
      50:70-77, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29193174
TI  - Antibacterial activity of polyphenolic fraction of Kombucha against Vibrio
      cholerae: targeting cell membrane.
AB  - : The present study was undertaken to determine the mechanism of antibacterial
      activity of a polyphenolic fraction, composed of mainly catechin and
      isorhamnetin, previously isolated from Kombucha, a 14-day fermented beverage of
      sugared black tea, against the enteropathogen Vibrio cholerae N16961. Bacterial
      growth was found to be seriously impaired by the polyphenolic fraction in a dose
      dependent manner. Scanning Electron Microscopy demonstrated morphological
      alterations in bacterial cells when exposed to the polyphenolic fraction in a
      concentration-dependent manner. Permeabilization assays confirmed that the
      fraction disrupted bacterial membrane integrity in both time- and dose-dependent
      manners, which were proportional to the production of intracellular reactive
      oxygen species (ROS). Furthermore, each of the polyphenols catechin and
      isorhamnetin showed the ability to permeate bacterial cell membranes by
      generating oxidative stress, thereby suggesting their role in the antibacterial
      potential of Kombucha. Thus, the basic mechanism of antibacterial activity of the
      Kombucha polyphenolic fraction against V. cholerae involved bacterial membrane
      permeabilization and morphological changes, which might be due to the generation
      of intracellular ROS. To the best of our knowledge, this is the first report on
      the investigation of antibacterial mechanism of Kombucha, which is mostly
      attributed to its polyphenolic content. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      emergence of multidrug-resistant Vibrio cholerae strains has hindered an
      efficient anti-Vibrio therapy. This study has demonstrated the membrane damage
      mediated antibacterial mechanism of Kombucha, a popular fermented beverage of
      sugared tea, which is mostly attributed to its polyphenolic content. This study
      also implies the exploitation of Kombucha as a potential new source of bioactive
      polyphenols against V. cholerae.

PMID- 29193175
TI  - Parallel probing of drug uptake of single cancer cells on a microfluidic device.
AB  - Drug resistance is frequently developing during treatment of cancer patients.
      Intracellular drug uptake is one of the important characteristics to understand
      mechanism of drug resistance. However, the heterogeneity of cancer cells requires
      the investigation of drug uptake at the single cell level. Here, we developed a
      microfluidic device for parallel probing of drug uptake. We combined a v-type
      valve and peristaltic pumping to select individual cells from a pool of prostate
      cancer cells (PC3) and place them successively in separate cell chambers in which
      they were exposed to the drug. Six different concentrations of doxorubicin, a
      naturally fluorescent anti-cancer drug, were created in loop-shaped reactors and
      exposed to the cell in closed 2 nL volume chambers. Monitoring every single cell
      over time in 18 parallel chambers revealed increased intracellular fluorescence
      intensity according to the dose of doxorubicin, as well as nuclear localization
      of the fluorescent drug after 2 h of incubation. The herein proposed technology
      demonstrated a first series of proof of concept experiments and it shows high
      potential to use for probing drug sensitivity of single cancer cell.

PMID- 29193177
TI  - Soft-Bodied Fossils Are Not Simply Rotten Carcasses - Toward a Holistic
      Understanding of Exceptional Fossil Preservation: Exceptional Fossil Preservation
      Is Complex and Involves the Interplay of Numerous Biological and Geological
      Processes.
AB  - Exceptionally preserved fossils are the product of complex interplays of
      biological and geological processes including burial, autolysis and microbial
      decay, authigenic mineralization, diagenesis, metamorphism, and finally
      weathering and exhumation. Determining which tissues are preserved and how biases
      affect their preservation pathways is important for interpreting fossils in
      phylogenetic, ecological, and evolutionary frameworks. Although laboratory decay
      experiments reveal important aspects of fossilization, applying the results
      directly to the interpretation of exceptionally preserved fossils may overlook
      the impact of other key processes that remove or preserve morphological
      information. Investigations of fossils preserving non-biomineralized tissues
      suggest that certain structures that are decay resistant (e.g., the notochord)
      are rarely preserved (even where carbonaceous components survive), and decay
      prone structures (e.g., nervous systems) can fossilize, albeit rarely. As we
      review here, decay resistance is an imperfect indicator of fossilization
      potential, and a suite of biological and geological processes account for the
      features preserved in exceptional fossils.

PMID- 29193176
TI  - Using voltage-sensor toxins and their molecular targets to investigate NaV 1.8
      gating.
AB  - Voltage-gated sodium (NaV ) channel gating is a complex phenomenon which involves
      a distinct contribution of four integral voltage-sensing domains (VSDI, VSDII,
      VSDIII and VSDIV). Utilizing accrued pharmacological and structural insights, we
      build on an established chimera approach to introduce animal toxin sensitivity in
      each VSD of an acceptor channel by transferring in portable S3b-S4 motifs from
      the four VSDs of a toxin-susceptible donor channel (NaV 1.2). By doing so, we
      observe that in NaV 1.8, a relatively unexplored channel subtype with distinctly
      slow gating kinetics, VSDI-III participate in channel opening whereas VSDIV can
      regulate opening as well as fast inactivation. These results illustrate the
      effectiveness of a pharmacological approach to investigate the mechanism
      underlying gating of a mammalian NaV channel complex.

PMID- 29193178
TI  - Integrated microfluidic biosensing platform for simultaneous confocal microscopy
      and electrophysiological measurements on bilayer lipid membranes and ion
      channels.
AB  - Combining high-resolution imaging and electrophysiological recordings is key for
      various types of experimentation on lipid bilayers and ion channels. Here, we
      propose an integrated biosensing platform consisting of a microfluidic cartridge
      and a dedicated chip-holder to conduct such dual measurements on suspended lipid
      bilayers, in a user-friendly manner. To illustrate the potential of the
      integrated platform, we characterize lipid bilayers in terms of thickness and
      fluidity while simultaneously monitoring single ion channel currents. For that
      purpose, POPC lipid bilayers are supplemented with a fluorescently-tagged
      phospholipid (NBD-PE, 1% mol) for Fluorescence Recovery After Photobleaching
      (FRAP) measurements and a model ion channel (gramicidin, 1 nM). These combined
      measurements reveal that NBD-PE has no effect on the lipid bilayer thickness
      while gramicidin induces thinning of the membrane. Furthermore, the presence of
      gramicidin does not alter the lipid bilayer fluidity. Surprisingly, in lipid
      bilayers supplemented with both probes, a reduction in gramicidin open
      probability and lifetime is observed compared to lipid bilayers with gramicidin
      only, suggesting an influence of NBD-PE on the gramicidin ion function.
      Altogether, our proposed microfluidic biosensing platform in combination with the
      herein presented multi-parametric measurement scheme paves the way to explore the
      interdependent relationship between lipid bilayer properties and ion channel
      function.

PMID- 29193179
TI  - Maximum likelihood estimation of influenza vaccine effectiveness against
      transmission from the household and from the community.
AB  - Influenza vaccination is recommended as the best way to protect against influenza
      infection and illness. Due to seasonal changes in influenza virus types and
      subtypes, a new vaccine must be produced, and vaccine effectiveness (VE) must be
      estimated, annually. Since 2010, influenza vaccination has been recommended
      universally in the United States, making randomized clinical trials unethical.
      Recent studies have used a monitored household cohort study design to determine
      separate VE estimates against influenza transmission from the household and
      community. We developed a probability model and accompanying maximum likelihood
      procedure to estimate vaccine-related protection against transmission of
      influenza from the household and the community. Using agent-based stochastic
      simulations, we validated that we can obtain maximum likelihood estimates of
      transmission parameters and VE close to their true values. Sensitivity analyses
      to examine the effect of deviations from our assumptions were conducted. We used
      our method to estimate transmission parameters and VE from data from a monitored
      household study in Michigan during the 2012-2013 influenza season and were able
      to detect a significant protective effect of influenza vaccination against
      community-acquired transmission.

PMID- 29193180
TI  - Considerations for analysis of time-to-event outcomes measured with error: Bias
      and correction with SIMEX.
AB  - For time-to-event outcomes, a rich literature exists on the bias introduced by
      covariate measurement error in regression models, such as the Cox model, and
      methods of analysis to address this bias. By comparison, less attention has been
      given to understanding the impact or addressing errors in the failure time
      outcome. For many diseases, the timing of an event of interest (such as
      progression-free survival or time to AIDS progression) can be difficult to assess
      or reliant on self-report and therefore prone to measurement error. For linear
      models, it is well known that random errors in the outcome variable do not bias
      regression estimates. With nonlinear models, however, even random error or
      misclassification can introduce bias into estimated parameters. We compare the
      performance of 2 common regression models, the Cox and Weibull models, in the
      setting of measurement error in the failure time outcome. We introduce an
      extension of the SIMEX method to correct for bias in hazard ratio estimates from
      the Cox model and discuss other analysis options to address measurement error in
      the response. A formula to estimate the bias induced into the hazard ratio by
      classical measurement error in the event time for a log-linear survival model is
      presented. Detailed numerical studies are presented to examine the performance of
      the proposed SIMEX method under varying levels and parametric forms of the error
      in the outcome. We further illustrate the method with observational data on HIV
      outcomes from the Vanderbilt Comprehensive Care Clinic.

PMID- 29193181
TI  - Simultaneous determination of tryptophan, kynurenine, kynurenic acid, xanthurenic
      acid and 5-hydroxytryptamine in human plasma by LC-MS/MS and its application to
      acute myocardial infarction monitoring.
AB  - Reliable methods for the determination of tryptophan and its metabolites are
      vital to the monitoring of biochemical states during the initiation and
      progression of cardiovascular disease. In the present study, a single-run liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the
      simultaneous determination of tryptophan (Trp) and its metabolites, including
      kynurenine (Kyn), kynurenic acid (KA), xanthurenic acid (XA) and 5
      hydroxytryptamine (5-HT), in human plasma. The plasma samples were prepared using
      a protein precipitation approach, and the chromatographic separation was
      performed by gradient elution on a C18 column within a total analysis time of 3.5
      min. The calibration ranges were 40-20,000 ng/mL for Trp, 4-2000 ng/mL for Kyn,
      0.2-100 ng/mL for KA, 0.4-200 ng/mL for XA and 1-500 ng/mL for 5-HT, and the
      precision and accuracy were acceptable. The evaluation of recovery and internal
      standard-normalized matrix effect proved that the sample preparation approach was
      effective and the matrix effect could be negligible. The newly developed method
      was successfully applied to the analysis of plasma samples from healthy
      individuals and myocardial infarction patients. The findings suggested that the
      plasma concentrations of Trp, Kyn, 5-HT as well as the concentration ratios of
      Kyn/Trp and Trp/5-HT might serve as biomarkers for the monitoring of acute
      myocardial infarction.

PMID- 29193182
TI  - Cognitive impairment and quality of life in patients with myotonic dystrophy type
      1.
AB  - INTRODUCTION: This study sought to clarify whether specific cognitive abilities
      are impaired in patients with myotonic dystrophy type 1 (DM1) as well as to
      investigate the relationships among quality of life (QoL), cognitive function,
      and psychological factors. METHODS: Sixty patients with DM1 were evaluated on
      cognitive functioning (abstract reasoning, attention/working memory, executive
      function, processing speed, and visuoconstructive ability), apathy, depression,
      excessive daytime sleepiness, fatigue, and QoL. QoL was assessed by 2 domains of
      the Muscular Dystrophy Quality of Life Scale (Psychosocial Relationships and
      Physical Functioning and Health). RESULTS: More than half of the patients
      exhibited cognitive impairment in attention/working memory, executive function,
      processing speed, and visuoconstructive ability. The Psychosocial Relationships
      factor was associated with processing speed, attention/working memory, and
      apathy, whereas depression and fatigue were associated with 2 QoL domains.
      DISCUSSION: Our study identified specific cognitive impairments in DM1. Specific
      cognitive functions and psychological factors may be potential contributors to
      QoL. Muscle Nerve 57: 742-748, 2018.

PMID- 29193183
TI  - Microbiological analysis of conjunctival secretion in anophthalmic cavity,
      contralateral eye and ocular prosthesis of patients with maxillofacial
      abnormalities.
AB  - : The purpose of this study was to identify and analyse the micro-organisms
      present in the conjunctival secretion in anophthalmic cavities of wearers of
      ocular prostheses, as well as on the prostheses used by them, correlating them
      with the microbiota of the contralateral eye. Nine patients with maxillofacial
      abnormalities, wearers of an acrylic resin ocular prosthesis participated in the
      study. Collections of conjunctival secretions and biofilm were performed on the
      prosthesis, anophthalmic cavity and contralateral eye for the mycological and
      bacterial analyses. The data were submitted to statistical analysis, performing a
      Kendall correlation test to identify the correlation between the collection site
      and the identified micro-organism (P < 0.05). It was verified that the most
      prevalent micro-organisms were the Staphylococcus aureus and Staphylococcus
      epidermidis, independent of the collection site, and that negative cultures for
      fungi were encountered in 85.2% of collections, independent of the region. It was
      not possible to establish a correlation among the types of micro-organisms and
      the collection sites. SIGNIFICANCE AND IMPACT OF THE STUDY: Some evidence
      suggests that the surface roughness of ocular prostheses can influence
      interactions with micro-organisms, with greater prejudicial consequences, such as
      the establishment of biofilms, which could lead to infections. Thus, it becomes
      extremely important to identify the micro-organisms present on the acrylic
      surfaces of ocular prostheses, as well as the microbiota of the anophthalmic
      cavity and contralateral eye of wearers of the same, so that subsequent control
      measures promote the homeostatic maintenance of the ocular region.

PMID- 29193184
TI  - Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma.
AB  - Treatment of myeloma is a long-term treatment mainly based on all-oral
      combinations of drugs. Because oral drugs have a more complex pharmacokinetics
      compared with IV treatments, an appropriate knowledge of the factors that may
      alter their systemic exposure is of particular clinical relevance. Both drug-drug
      interactions, food-effect, and dose-adaptation in renal and hepatic impairment
      may influence the systemic drug levels with a potential impact on drug efficacy
      or safety. Moreover, a better control of drug exposure may improve the side
      effect profiles of these treatments with a favourable impact on patient
      compliance. Furthermore, as long-term treatments, these drugs may also alter the
      systemic exposure of coadministered medications in these rather old patients. The
      aim of this review was to identify the factors modifying the systemic exposure of
      oral drugs used in myeloma by focusing on the pharmacokinetic drug-drug
      interactions and the effects of renal and hepatic impairment and of food impact.

PMID- 29193185
TI  - Ketamine Infusion for Adjunct Sedation in Mechanically Ventilated Adults.
AB  - BACKGROUND: Many critically ill patients receive ketamine for adjunct sedation
      despite a paucity of evidence on its use, dosing, and monitoring in this setting.
      OBJECTIVE: To describe the dosing and safety considerations of ketamine for
      adjunct sedation in a population of mechanically ventilated critically ill
      patients targeting light sedation. METHODS: We conducted a retrospective review
      of mechanically ventilated patients receiving continuous ketamine infusion
      between January 2012 and April 2016. Data included dosing, effect of ketamine on
      other sedatives, total sedative use, Riker Sedation-Agitation Scale (SAS) scores,
      adverse drug reactions (ADRs), and hemodynamic variables. RESULTS: Ninety-one
      patients were included in the analysis. Ketamine was infused at a median dosage
      of 0.41 mg/kg/hour (range 0.04-2.5 mg/kg/hr) for up to 14.7 days (median 2.8
      days). Concomitant sedatives were reduced or discontinued, without the initiation
      of an additional sedative, in 57 patients (63%) within 24 hours of initiating
      ketamine. Propofol was most commonly discontinued (16 patients, 36%), followed by
      benzodiazepines (12 patients, 27%). There was an increase in the number of SAS
      scores documented in goal in the 24-hour period after ketamine initiation
      compared with the immediate 24 hours before (61% vs 55%, p=0.001). Patients were
      less frequently agitated, defined as SAS >4, after the initiation of ketamine
      (27% vs 33%, p=0.005). Seven patients (7.7%) required discontinuation of ketamine
      infusion for an ADR. There were no significant changes in hemodynamic variables
      after the initiation of ketamine. CONCLUSIONS: Continuous ketamine infusion for
      adjunct light sedation was well tolerated in a cohort of critically ill adults,
      with an acceptable safety profile. Prospective studies of ketamine infusion are
      warranted to further establish its efficacy as a sedative in this population.

PMID- 29193186
TI  - CE-XRF-initial steps toward a non-invasive elemental sensitive detector for
      liquid separations.
AB  - The toxicity, bioavailability, and mobilization of elements within the biosphere
      is dependent on its species. CE has emerged as a strong separation technique for
      elemental speciation. Conventionally, CE has been coupled with UV-vis, C4 D, PIXE
      (proton-induced X-ray emission), and ICP-MS. UV-vis and C4 D are not elemental
      sensitive detection methods, PIXE requires the etching of the detection window
      resulting in a very brittle capillary, and ICP-MS is an expensive large footprint
      instrument. Here, we aim to develop an elemental specific detector, XRF (X-ray
      fluorescence spectrometry), for use with CE. A custom-built micro-XRF was tested
      and static LODs were determined for 19 elements (Ca-U) with both unmodified (20
      926 ppm) and modified capillaries (20-291 ppm). A custom-built CE was combined
      with the micro-XRF and separation of Ca2+ and Co2+ was obtained. Sr2+ coeluted
      with Ca2+ in the mixture, but because of the elemental sensitivity of XRF, the Sr
      and Ca signals could be separated. After successful testing of the micro-XRF, the
      feasibility of using a low-cost X-ray source and detector was tested. Even lower
      LODs were obtained for Ga and Rb, showing the feasibility of a smaller, low-cost
      XRF unit as an elemental specific detector. However, the buffer selection that
      can be conveniently used with XRF is currently limited due to capillary
      corrosion, likely correlated to radiolysis.

PMID- 29193187
TI  - Same-level fall injuries in US workplaces by age group, gender, and industry.
AB  - BACKGROUND: As the workforce ages, occupational injuries from falls on the same
      level will increase. Some industries may be more affected than others. METHODS:
      We conducted a cross-sectional study using data from the Bureau of Labor
      Statistics to estimate same-level fall injury incidence rates by age group,
      gender, and industry for four sectors: 1) healthcare and social assistance; 2)
      manufacturing; 3) retail; and 4) transportation and warehousing. We calculated
      rate ratios and rate differences by age group and gender. RESULTS: Same-level
      fall injury incidence rates increase with age in all four sectors. However,
      patterns of rate ratios and rate differences vary by age group, gender, and
      industry. Younger workers, men, and manufacturing workers generally have lower
      rates. CONCLUSIONS: Variation in incidence rates suggests there are unrealized
      opportunities to prevent same-level fall injuries. Interventions should be
      evaluated for their effectiveness at reducing injuries, avoiding gender- or age
      discrimination and improving work ability.

PMID- 29193188
TI  - Spatially Representing Vulnerability to Extreme Rain Events Using Midwestern
      Farmers' Objective and Perceived Attributes of Adaptive Capacity.
AB  - Potential climate-change-related impacts to agriculture in the upper Midwest pose
      serious economic and ecological risks to the U.S. and the global economy. On a
      local level, farmers are at the forefront of responding to the impacts of climate
      change. Hence, it is important to understand how farmers and their farm
      operations may be more or less vulnerable to changes in the climate. A
      vulnerability index is a tool commonly used by researchers and practitioners to
      represent the geographical distribution of vulnerability in response to global
      change. Most vulnerability assessments measure objective adaptive capacity using
      secondary data collected by governmental agencies. However, other scholarship on
      human behavior has noted that sociocultural and cognitive factors, such as risk
      perceptions and perceived capacity, are consequential for modulating people's
      actual vulnerability. Thus, traditional assessments can potentially overlook
      people's subjective perceptions of changes in climate and extreme weather events
      and the extent to which people feel prepared to take necessary steps to cope with
      and respond to the negative effects of climate change. This article addresses
      this knowledge gap by: (1) incorporating perceived adaptive capacity into a
      vulnerability assessment; (2) using spatial smoothing to aggregate individual
      level vulnerabilities to the county level; and (3) evaluating the relationships
      among different dimensions of adaptive capacity to examine whether perceived
      capacity should be integrated into vulnerability assessments. The result suggests
      that vulnerability assessments that rely only on objective measures might miss
      important sociocognitive dimensions of capacity. Vulnerability indices and maps
      presented in this article can inform engagement strategies for improving
      environmental sustainability in the region.

PMID- 29193190
TI  - Indoor allergen levels in settled airborne dust are higher in day-care centers
      than at home.
AB  - BACKGROUND: Early-life sensitization to indoor allergens predicts asthma
      development. The aim of this study was to compare allergen concentrations in day
      care centers (DCC) with those in private homes. METHODS: Settled airborne dust
      was collected 4 times a year from 20 German DCC (620 samples) and from the homes
      of children and day-care workers (602 samples) using electrostatic dust
      collectors (EDC). The samples were analyzed with fluorescence enzyme immunoassays
      recognizing domestic mite allergens (DM), Fel d 1, Can f 1, and Mus m 1. Pet
      allergen thresholds that discriminate samples from homes with cats or dogs from
      those without were calculated using receiver-operating characteristics.
      Influences on allergen levels were analyzed using multilevel models. RESULTS:
      Allergen loads were on average higher in DCC than in homes. In DCC, 96% of the
      samples were positive for DM, 95% for Can f 1, 90% for Fel d 1, and 83% for Mus m
      1. In homes, 84% contained DM, 48.5% Can f 1, 33% Fel d 1, and 43% Mus m 1. The
      threshold level for homes with dogs was 75 ng/m2 Can f 1 (96.8% sensitivity, 96%
      specificity), and the threshold level for homes with cats was 46 ng/m2 Fel d 1
      (92% sensitivity, 94.9% specificity). In DCC, Can f 1 and Fel d 1 loads were
      higher than these thresholds in 37% and 54% of the samples, respectively.
      Allergen levels were significantly influenced by the season and room type;
      however, carpets on floors had no influence. CONCLUSIONS: Mite, mouse, cat, and
      dog allergens were mostly higher in DCC than in homes. Exposure to dog and cat
      allergens in DCC often reached levels of households with pets.

PMID- 29193189
TI  - Chemical characterization of 21 species of marine macroalgae common in Norwegian
      waters: benefits of and limitations to their potential use in food and feed.
AB  - BACKGROUND: In the past few years, much effort has been invested into developing
      a new blue economy based on harvesting, cultivating and processing marine
      macroalgae in Norway. Macroalgae have high potential for a wide range of
      applications, e.g. as source of pharmaceuticals, production of biofuels or as
      food and feed. However, data on the chemical composition of macroalgae from
      Norwegian waters are scant. This study was designed to characterize the chemical
      composition of 21 algal species. Both macro- and micronutrients were analysed.
      Concentrations of heavy metals and the metalloid arsenic in the algae were also
      quantified. RESULTS: The results confirm that marine macroalgae contain nutrients
      which are relevant for both human and animal nutrition, the concentrations
      whereof are highly dependent on species. Although heavy metals and arsenic were
      detected in the algae studied, concentrations were mostly below maximum allowed
      levels set by food and feed legislation in the EU. CONCLUSION: This study
      provides chemical data on a wide range of algal species covering the three
      taxonomic groups (brown, red and green algae) and discusses both benefits of and
      potential limitations to their use for food and feed purposes. (c) 2017 The
      Authors. Journal of The Science of Food and Agriculture published by John Wiley &
      Sons Ltd on behalf of Society of Chemical Industry.

PMID- 29193191
TI  - Treatment of tracheoesophageal fistula after laryngectomy by a customized
      tracheal prosthesis.

PMID- 29193192
TI  - Ensuring Clinical Efficacy and Patient Safety With Repaired Ultrasound Probes.

PMID- 29193193
TI  - Which Fire to Extinguish First? A Risk-Informed Approach to Emergency Response in
      Oil Terminals.
AB  - The performance of fire protection measures plays a key role in the prevention
      and mitigation of fire escalation (fire domino effect) in process plants. In
      addition to passive and active safety measures, the intervention of firefighting
      teams can have a great impact on fire propagation. In the present study, we have
      demonstrated an application of dynamic Bayesian network to modeling and safety
      assessment of fire domino effect in oil terminals while considering the effect of
      safety measures in place. The results of the developed dynamic Bayesian network
      prior and posterior probabilities-have been combined with information theory, in
      the form of mutual information, to identify optimal firefighting strategies,
      especially when the number of fire trucks is not sufficient to handle all the
      vessels in danger.

PMID- 29193194
TI  - Impact of individual behaviour change on the spread of emerging infectious
      diseases.
AB  - Human behaviour plays an important role in the spread of emerging infectious
      diseases, and understanding the influence of behaviour changes on epidemics can
      be key to improving control efforts. However, how the dynamics of individual
      behaviour changes affects the development of emerging infectious disease is a key
      public health issue. To develop different formula for individual behaviour change
      and introduce how to embed it into a dynamic model of infectious diseases, we
      choose A/H1N1 and Ebola as typical examples, combined with the epidemic reported
      cases and media related news reports. Thus, the logistic model with the health
      belief model is used to determine behaviour decisions through the health belief
      model constructs. Furthermore, we propose 4 candidate infectious disease models
      without and with individual behaviour change and use approximate Bayesian
      computation based on sequential Monte Carlo method for model selection. The main
      results indicate that the classical compartment model without behaviour change
      and the model with average rate of behaviour change depicted by an exponential
      function could fit the observed data best. The results provide a new way on how
      to choose an infectious disease model to predict the disease prevalence trend or
      to evaluate the influence of intervention measures on disease control. However,
      sensitivity analyses indicate that the accumulated number of hospital
      notifications and deaths could be largely reduced as the rate of behaviour change
      increases. Therefore, in terms of mitigating emerging infectious diseases, both
      media publicity focused on how to guide people's behaviour change and positive
      responses of individuals are critical.

PMID- 29193195
TI  - Presence of stratum corneum serum in non-palmoplantar psoriasis.
AB  - BACKGROUND: Psoriasis is a common, chronic skin eruption characterized by
      abnormal hyperproliferation of the epidermis. When assessing psoriasis
      histologically, it is historically considered a "dry" disease, with significant
      amounts of serum not expected within lesional stratum corneum. However, this
      specific feature is not often mentioned within the literature. A retrospective
      study was undertaken to assess prevalence of serum within stratum corneum in
      cases of non-palmoplantar psoriasis. METHODS: We evaluated 27 specimens diagnosed
      histologically as psoriasis between January 2015 and June 2016. In addition to
      serum, we assessed for psoriasiform hyperplasia, hypogranulosis, suprapapillary
      thinning and parakeratosis with neutrophils. The cases were then categorized as
      either diagnostic for, or consistent with, psoriasis and were followed up with
      clinicians to assess whether the clinical course was consistent with psoriasis.
      RESULTS: A total of 27 hematoxylin and eosin (H&E)-stained biopsies were examined
      from 21 patients, with periodic acid-Schiff (PAS) performed on 20 of the
      biopsies. Of these, 12 biopsies had serum present (44.4%). Of the 12 lesions
      considered to clinically and histologically represent psoriasis, 5 (41.7%) had
      serum. CONCLUSION: Our results suggest serum within stratum corneum is possibly
      an acceptable feature within the spectrum of psoriasis histopathology and should
      not necessarily detract from the diagnosis.

PMID- 29193196
TI  - Extracranial and Intracranial Ultrasonographic Findings in Posterior Circulation
      Infarction.
AB  - OBJECTIVES: Patients with posterior circulation infarction are at higher risk of
      early recurrent stroke, especially those with vertebrobasilar stenosis or
      hypoplasia. The clinical presentations of this condition vary over a broad range,
      making diagnosis and treatment a challenge. Hemodynamic changes and stenosis
      detected by ultrasonography (US) are sensitive and important indicators for
      further evaluation. In this study, we correlated extracranial and intracranial US
      characteristics with brain magnetic resonance imaging (MRI) in patients with
      posterior circulation infarction. METHODS: Inpatients with acute ischemic stroke
      who received both MRI and US were enrolled. Baseline characters, underlying
      disorders, the ischemic territory, and vascular stenosis on MRI were recorded.
      Series of US data, including flow volume, diameter, mean velocity, and
      pulsatility index, were analyzed. Patients with new infarction over the medulla,
      pons, midbrain, or cerebellum were enrolled as the posterior circulation
      infarction group. Patients with pure anterior circulation infarction were also
      enrolled. RESULTS: A total of 210 patients with anterior circulation infarction
      (mean age +/- SD, 66.24 +/- 12.88 years) and 143 with posterior circulation
      infarction (mean age, 65.82 +/- 11.39 years) were enrolled. Significant higher
      frequencies of vertebral artery hypoplasia and decreased intracranial
      vertebrobasilar velocity in the posterior circulation infarction group (44.75%
      and 64.33%, respectively) were documented (P < .0001; P = .035). Ischemic lesion
      distributions were correlated with vertebral artery hypoplasia (55.56 %) and low
      vertebral and basilar artery velocities (44.44% and 25.53%), as documented by US.
      A low vertebrobasilar velocity was highly correlated with MRI-documented vascular
      stenosis (53.06%). CONCLUSIONS: Vertebral artery hypoplasia and a low velocity in
      the intracranial vertebrobasilar system on US might change the treatment of
      patients with posterior circulation infarction for primary and secondary
      prevention.

PMID- 29193197
TI  - Signalling Profiles of Blood Leucocytes in Sepsis and in Acute Pancreatitis in
      Relation to Disease Severity.
AB  - Intracellular signalling in blood leucocytes shows multiple aberrations in acute
      pancreatitis (AP) complicated by organ dysfunction (OD). We studied whether the
      aberrations associate with severity of AP and occur in sepsis complicated by OD.
      The study comprises 14 sepsis patients (11 with shock), 18 AP patients (nine
      mild; six moderately severe; three severe) and 28 healthy volunteers. Within 48 h
      after admission to hospital, phosphorylation of nuclear factor-KB (NF-KB), signal
      transducers and activators of transcription (STATs) 1,3, and extracellular signal
      regulated kinases 1/2 were measured from stimulated or non-stimulated leucocytes
      using phosphospecific whole blood flow cytometry. In sepsis, as compared with
      healthy subjects, phosphorylated NF-KB levels of monocytes promoted by bacterial
      lipopolysaccharides, tumour necrosis factor or Escherichia coli cells were lower
      (P < 0.001 for all), pSTAT1 levels of monocytes promoted by IL-6 were lower (P <
      0.05 for all), and STAT3 was constitutively phosphorylated in monocytes,
      neutrophils and lymphocytes (P < 0.001 for all). In AP, severity was associated
      with proportions of pSTAT1-positive monocytes and lymphocytes promoted by IL-6 (P
      < 0.01 for both), constitutive STAT3 phosphorylation in neutrophils (P < 0.05),
      but not with any of the pNF-KB levels. Monocyte pSTAT3 fluorescence intensity,
      promoted by IL-6, was lower in sepsis and AP patients with OD than in AP patients
      without OD (P < 0.001). Collectively, signalling aberrations in sepsis with OD
      mimic those described previously in AP with OD. Possibility that aberrations in
      STAT1 and STAT3 pathways provide novel markers predicting evolution of OD
      warrants studies including patients presenting without OD but developing it
      during follow-up.

PMID- 29193198
TI  - The DNA-methyltransferase inhibitor 5-aza-2-deoxycytidine affects Humicola grisea
      enzyme activities and the glucose-mediated gene repression.
AB  - Humicola grisea var. thermoidea (Hgvt) is a thermophilic ascomycete that produces
      lignocellulolytic enzymes and it is proposed for the conversion of agricultural
      residues into useful byproducts. Drugs that inhibit the DNA methyltransferases
      (DNMTs) activity are employed in epigenetic studies but nothing is known about a
      possible effect on the production of fungal enzymes. We evaluated the effect of 5
      aza-2'-deoxycytidine (5-Aza; a chemical inhibitor of DNMTs activity) on the
      secreted enzyme activity and on the transcription of cellulase and xylanase genes
      from Hgvt grown in agricultural residues and in glucose. Upon cultivation on
      wheat bran (WB), the drug provoked an increase in the xylanase activity at 96 h.
      When Hgvt was grown in glucose (GLU), a repressor of Hgvt glycosyl hydrolase
      genes, 5-Aza led to increased transcript accumulation for the cellobiohydrolases
      and for the xyn2 xylanase genes. In WB, 5-Aza enhanced the expression of the
      transcription factor CreA gene. Growth on WB or GLU, in presence of 5-Aza, led to
      a significant increase in transcripts of the pH-response regulator PacC gene. To
      our knowledge, this is the first report on the effect of a DNMT inhibitor in the
      production of fungal plant cell wall degradation enzymes.

PMID- 29193199
TI  - MUC1- and Survivin-based DNA Vaccine Combining Immunoadjuvants CpG and
      interleukin-2 in a Bicistronic Expression Plasmid Generates Specific Immune
      Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model.
AB  - DNA vaccination is a promising cancer treatment due to its safety, but poor
      immunogenicity limits its application. However, immunoadjuvants, heterogeneous
      prime-boost strategies and combination with conventional treatments can be used
      to improve the antitumour immune effects. A CpG motif and interleukin-2 (IL-2)
      cytokine are often used as adjuvants. In this study, a DNA vaccine containing a
      CpG motif was constructed to evaluate its adjuvant effect. The results show that
      the cytotoxicity of the DNA vaccine was increased fivefold, and survival lifetime
      was prolonged twofold by the CpG motif adjuvant. To simplify the industrial
      production process, a bicistronic plasmid was constructed to carry the fusion
      genes of survivin/MUC1 (MS) and IL-2 and with a CpG motif in its backbone. The
      results showed that the antitumour effect of the bicistronic vaccine was the same
      as that of the two vaccine co-injected regime. Furthermore, the vaccine could
      suppress metastatic tumour foci by 69.1% in colorectal carcinoma-bearing mice.
      Moreover, the vaccine induced survivin- and MUC1-specific immune responses in
      splenocytes and induced the immune promoting factor CCL-19 and GM-CSF
      upregulated, while metastatic-associated factor MMP-9 and immunosuppressing
      factor PD-L1 downregulated in tumour tissue. When combining the vaccine with the
      chemotherapy drug oxaliplatin, the survival was prolonged by about 2.5-fold. In
      conclusion, the DNA vaccine containing a CpG motif in bicistronic form showed
      good effects on colorectal cancer by inhibiting both tumour growth and
      metastasis, and combination with oxaliplatin could improve its antitumour
      effects.

PMID- 29193200
TI  - Rapid identification of microorganisms from platelet concentrates by matrix
      assisted laser desorption ionization time-of-flight mass spectrometry after short
      term incubation on liquid medium.
AB  - BACKGROUND: Platelets (PLTs) are especially affected by the risk of bacterial
      contamination. Matrix-assisted laser desorption ionization time-of-flight (MALDI
      TOF) is an accurate method for the routine identification of bacterial isolates
      in microbiology laboratories. We directly applied the MALDI-TOF method to
      bacterial detection in PLTs. In this study, we evaluated the sensitivity,
      specificity, and speed of a direct MALDI-TOF approach compared to the
      conventional method BACTEC. STUDY DESIGN AND METHODS: Eight bacteria associated
      with PLT contamination, cited by the ISBT on transfusion-transmitted infectious
      diseases, were spiked into PLTs for a final concentration of approximately 100
      CFU/bag (n = 5 for each strain). The PLTs were then agitated for 24 hours. One
      milliliter of PLTs was incubated in a shaker incubator for 8 hours at 37 degrees
      C with 1 mL of trypticase soy broth (TSB). The spectra were analyzed using the
      MALDI Biotyper software. As a control, 8 mL of PLTs incubated into BACTEC bottles
      and a positive bottle were subcultured to ensure identification of bacterial
      growth. RESULTS: Regardless of the strain of PLTs tested, MALDI-TOF analysis made
      detection and early identification possible at 8 hours. Analysis by BACTEC of
      PLTs infected with Escherichia coli, Bacillus cereus, and Providencia stuartii
      made early identification possible. For the remaining bacteria, the detection
      time by BACTEC was significantly longer than 8 hours. CONCLUSION: We demonstrated
      the possibility of detecting bacteria in PLTs using a standardized culture step
      in TSB with MALDI-TOF, regardless of the strain, with the same specificity and
      analytical sensitivity and with a time to results of 12 hours. This direct method
      presented rapid and reliable results.

PMID- 29193201
TI  - Red tattoo-related mycosis fungoides-like CD8+ pseudolymphoma.
AB  - Cutaneous reactions to red tattoo pigment rarely manifest as pseudolymphomatous
      reactions. We describe an exceedingly rare case of red tattoo-related T-cell
      predominant pseudolymphoma microscopically mimicking mycosis fungoides. Careful
      clinicopathological correlation was required to obtain the correct diagnosis and
      aid in an effective treatment course.

PMID- 29193202
TI  - Multifunctional in vivo imaging for monitoring wound healing using swept-source
      polarization-sensitive optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: Wound healing involves a complex and dynamic biological
      process in response to tissue injury. Monitoring of the cascade of cellular
      events is useful for wound management and treatment. The aim of this study is to
      demonstrate the potential of multifunctional polarization-sensitive optical
      coherence tomography (PS-OCT) to longitudinally monitor the self-healing process
      in a murine cutaneous wound model. MATERIALS AND METHODS: A multi-functional PS
      OCT system based on swept source OCT configuration (1,310 nm central wavelength)
      was designed to obtain simultaneously microstructural, blood perfusion, and
      birefringent information of a biological tissue in vivo. A 1-mm-diameter wound
      was generated in a mouse pinna with a complete biopsy punch. Afterwards, the self
      healing process of the injured tissue was observed every week over 6-week period
      using the multifunctional system to measure changes in the tissue birefringence.
      Further OCT angiography (OCTA) was used in post data processing to obtain blood
      perfusion information over the injured tissue. RESULTS: Three complementary
      images indicating the changes in anatomical, vascular, and birefringent
      information of tissue around wound were simultaneously provided from a 3
      dimensional (3-D) PS-OCT data set during the wound repair over 1 month.
      Specifically, inflammatory and proliferative phases of wound healing were
      characterized by thickened epidermal tissue (from OCT images) and angiogenesis
      (from OCT angiography images) around wound. Also, it was observed that the
      regenerating tissues had highly realigned birefringent structures (from PS-OCT
      images). CONCLUSION: This preliminary study suggests that the proposed multi
      functional imaging modality has a great potential to improve the understanding of
      wound healing through non-invasive, serial monitoring of vascular and tissue
      responses to injury. Lasers Surg. Med. 50:213-221, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29193203
TI  - Nuclear and cytoplasmic features in the diagnosis of Clark's nevi.
AB  - BACKGROUND: Interpretation of Clark's nevi has generated debate over the years;
      although criteria have been proposed for grading morphological features of
      melanocytes, there is still confusion and variability in the assessment of these
      lesions. METHODS: This is a retrospective observational study conducted on 100
      Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all
      blinded and randomized photomicrographs of both the Clark's nevi and melanomas
      for the presence of 14 cytologic features. Subsequently, a multivariate model was
      used to obtain sensitivity and specificity. RESULTS: Clark's nevi showed a
      significantly higher frequency of absent-or-inconspicuous nucleoli over melanoma,
      whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth
      nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular
      nucleus with rounded nucleoli were found significantly higher in frequency in
      melanomas. CONCLUSION: Our data suggest that nuclear alterations are of value in
      the differentiation of atypical nevi from melanoma.

PMID- 29193206
TI  - On the necessity and design of studies comparing statistical methods.

PMID- 29193204
TI  - Engineered agrin attenuates the severity of experimental autoimmune myasthenia
      gravis.
AB  - INTRODUCTION: Agrin is essential for the formation and maintenance of
      neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural
      agrin. In this study, we determined the effects of NT-1654 on the severity of
      experimental autoimmune myasthenia gravis (EAMG). METHODS: EAMG was induced in
      female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR)
      and complete Freund's adjuvant (CFA). NT-1654 was dissolved in phosphate-buffered
      saline (PBS) and injected daily subcutaneously into tAChR immunized rats during
      the first 10 days after immunization, and then every other day for the following
      20 days. RESULTS: We showed that NT-1654 attenuated clinical severity,
      effectively promoted the clustering of AChRs at NMJs, and alleviated the
      impairment of NMJ transmission and the reduction of muscle-specific kinase (MuSK)
      in EAMG rats. DISCUSSION: We demonstrated that NT-1654 attenuated clinical
      severity, effectively promoted the clustering of AChRs at NMJs, and alleviated
      the impairment of NMJ transmission and the reduction of muscle-specific kinase
      (MuSK) in EAMG rats. Muscle Nerve 57: 814-820, 2018.

PMID- 29193209
TI  - Cicatricial organising pneumonia mimicking a fibrosing interstitial pneumonia.
AB  - AIMS: Organising pneumonia (OP) is composed of loose granulation tissue plugs in
      distal airspaces; these disappear with steroid treatment. Recently a variant
      labelled 'cicatricial' OP has been described in which the granulation tissue
      organised to much denser fibrous tissue but still retained the usual pattern of
      OP. Here we report 10 patients thought to have an interstitial lung disease, and
      who on biopsy had a variant of cicatricial OP characterised by linear bands or
      small nodular masses of dense fibrous tissue that does not resemble ordinary OP.
      METHODS AND RESULTS: The bands/nodules were usually distributed randomly but
      occasionally resembled fibrotic non-specific interstitial pneumonia in local
      areas. Small foci of loose granulation tissue at the edge of the fibrotic bands
      sometimes mimicked fibroblast foci. Recognisable conventional OP was always
      present, but often in very small amounts. Four cases, including one patient with
      Ehlers-Danlos syndrome, showed formation of bone in the fibrotic bands and
      nodules. On computerised tomography (CT) scan of the chest some cases looked like
      typical OP, but some demonstrated only irregularly distributed linear opacities,
      sometimes with associated calcification. Follow-up imaging on six cases showed
      that the process either markedly improved or remained stable over time; no case
      had progressive disease. CONCLUSIONS: Cicatricial OP with this pathological
      pattern represents an uncommon form of OP that appears to be a generally benign
      process which may have persisting linear opacities on CT scan but that does not
      progress; however, it can be confused on biopsy and CT with a fibrosing
      interstitial pneumonia.

PMID- 29193208
TI  - Granular cell basal cell carcinoma: A case report.
AB  - Granular cell basal cell carcinoma (BCC) is a rare histopathological variant of
      BCC. Our review of the literature revealed only 17 previously identified cases.
      We report the case of a 47-year-old man who presented with an ulceration on his
      right upper lip which was subsequently removed. Histopathologic examination
      revealed that the tumor was composed solely of granular cells with numerous
      cytoplasmic eosinophilic round inclusion bodies. Mitotic figures ranged from 8 to
      15 per 10 high-power fields, with a Ki-67 proliferative index of ~5%.
      Immunohistochemically, the granular cells showed strong and diffuse positivity
      for Ber-EP4, pan-cytokeratin, AE1/AE3, CK5/6 and p63 and focal positivity for
      lysozyme, CD68 (clone KP1) and Bcl-2.

PMID- 29193210
TI  - What is the value of Values Based Recruitment for nurse education programmes?
AB  - AIM: A discussion of issues associated with Values Based Recruitment (VBR) for
      nurse education programmes. BACKGROUND: Values Based Recruitment is a mandatory
      element in selection processes of students for Higher Education healthcare
      courses in England, including all programmes across nursing. Students are
      selected on the basis that their individual values align with those presented in
      the Constitution of the National Health Service. However, there are issues
      associated with the use of values as selection criteria that have been
      insufficiently addressed. These are discussed. DESIGN: Discussion paper. DATA
      SOURCES: This article is based on documents published on the website of the
      executive body responsible for the implementation of a policy regarding VBR in
      Higher Education Institutions up until June 2017 and our evaluation of the
      conceptualisation of VBR, underpinned by contemporary theory and literature.
      IMPLICATIONS FOR NURSING: Values Based Recruitment influences who is accepted
      onto a nurse education programme, but there has been limited critical evaluation
      regarding the effectiveness of employing values as selection criteria. Values are
      subject to interpretation and evidence regarding whether or how VBR will improve
      practice and care is lacking. The issues discussed in this article show that
      Higher Education Institutions offering nursing courses, whether in England or in
      other countries, should be critical and reflective regarding the implementation
      of VBR methods. CONCLUSION: We call for a debate regarding the meaning and
      implications of VBR and further research regarding its validity and
      effectiveness.

PMID- 29193212
TI  - Meta-analysis for the comparison of two diagnostic tests-A new approach based on
      copulas.
AB  - Meta-analysis of diagnostic studies is still field of ongoing biometrical
      research. Especially, clinical researchers call for methods that allow for a
      comparison of different diagnostic tests to a common gold standard. Focussing on
      two diagnostic tests, the main parameters of interest are differences of
      sensitivities and specificities (with their corresponding confidence intervals)
      between the two diagnostic tests while accounting for the various associations
      across the two tests and the single studies. Similar to our previous work using
      generalized linear mixed models to this task, we propose a model with a
      quadrivariate response consisting of the two sensitivities and the two
      specificities of both tests. This new approach uses the ideas of copula
      modelling, and especially a quadrivariate Gaussian copula and a quadrivariate
      vine copula, which is built from bivariate Plackett copulas. The different
      copulas are compared in a simulation study and illustrated by the application of
      population-based screening for type 2 diabetes.

PMID- 29193211
TI  - Is tranexamic acid exposure related to blood loss in hip arthroplasty? A
      pharmacokinetic-pharmacodynamic study.
AB  - AIMS: Tranexamic acid (TXA) is an antifibrinolytic agent, decreasing blood loss
      in hip arthroplasty. The present study investigated the relationship between TXA
      exposure markers, including the time above the in vitro threshold reported for
      inhibition of fibrinolysis (10 mg l-1 ), and perioperative blood loss. METHODS:
      Data were obtained from a prospective, double-blind, parallel-arm, randomized
      superiority study in hip arthroplasty. Patients received a preoperative
      intravenous bolus of TXA 1 g followed by a continuous infusion of either TXA 1 g
      or placebo over 8 h. A population pharmacokinetic study was conducted to quantify
      TXA exposure. RESULTS: In total, 827 TXA plasma concentrations were measured in
      166 patients. A two-compartment model fitted the data best, total body weight
      determining interpatient variability in the central volume of distribution.
      Creatinine clearance accounted for interpatient variability in clearance. At the
      end of surgery, all patients had TXA concentrations above the therapeutic target
      of 10 mg l-1 . The model-estimated time during which the TXA concentration was
      above 10 mg l-1 ranged from 3.3 h to 16.3 h. No relationship was found between
      blood loss and either the time during which the TXA concentration exceeded 10 mg
      l-1 or the other exposure markers tested (maximum plasma concentration, area
      under the concentration-time curve). CONCLUSION: In hip arthroplasty, TXA plasma
      concentrations were maintained above 10 mg l-1 during surgery and for a minimum
      of 3 h with a preoperative TXA dose of 1 g. Keeping TXA concentrations above this
      threshold up to 16 h conferred no advantage with regard to blood loss.

PMID- 29193214
TI  - In Grateful Recognition of Our Editorial Board.

PMID- 29193213
TI  - First evidence of viral and bacterial oyster pathogens in the Brazilian coast.

PMID- 29193216
TI  - In pursuit of peak animal welfare; the need to prioritize the meaningful over the
      measurable.
AB  - Despite the diversity of animal welfare definitions, most recognise the
      centrality of the feelings of animals which are currently impossible to measure
      directly. As a result, animal welfare assessment is heavily reliant upon the
      indirect measurement of factors that either affect what animals feel, or are
      effected by how they feel. Physiological and health orientated measures have
      emerged as popular metrics for assessing welfare because they are quantifiable,
      can effect and be affected by how animals feel and have merits regardless of
      their relationship to the feelings of animals. However, their popularity in
      animal welfare assessment has led to them having a disproportionate influence on
      animal management to the detriment of animal welfare in numerous instances. Here,
      the case is made that a tension exists between management that prioritizes
      aspects of care reflecting popular animal welfare metrics such as those relating
      to physical health, and management that emphasizes psychological wellbeing. By re
      examining the relative merits of physical and psychological priorities in animal
      management, an alternate animal welfare paradigm emerges less tied to traditional
      welfare metrics. This paradigm theorizes about the possibility for an optimal
      animal welfare state to exist where managed animal populations provided essential
      psychological outlets but protected from key physical stressors routinely
      experienced in the wild, might experience higher levels of welfare than wild
      populations would routinely experience. The proposition that optimal animal
      welfare could theoretically be achieved in well managed and well designed captive
      environments challenges a widely held ethical perspective that captivity is
      inherently bad for animal welfare.

PMID- 29193217
TI  - Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter
      pylori eradication - a prospective study for up to 10 years.
AB  - BACKGROUND: Atrophic gastritis and intestinal metaplasia are premalignant
      conditions for gastric cancer. Their reversibility by Helicobacter pylori
      eradication remains controversial. AIM: To evaluate the reversibility of atrophic
      gastritis and intestinal metaplasia by H. pylori eradication with long-term
      follow-up. METHODS: 598 subjects were prospectively enrolled and followed for up
      to 10 years. They were categorised as H. pylori-negative (n = 65), H. pylori non
      eradicated (n = 91), and H. pylori-eradicated (n = 442). Histological assessment
      was performed for antrum and corpus by Sydney classification. RESULTS:
      Histological follow-up was performed regularly at 1, 2, 3-4 and >=5 years, with
      mean follow-up of 1.07 +/- 0.21, 2.29 +/- 0.83, 3.93 +/- 1.02, and 6.45 +/- 1.28
      years, respectively. Atrophic gastritis in antrum and corpus gradually and
      significantly (both P < .05 for all timepoints) improved only in the H. pylori
      eradicated group compared to that at baseline. Significant difference in atrophic
      gastritis between H. pylori-eradicated and H. pylori-negative groups disappeared
      from 1-year follow-up. Similarly, intestinal metaplasia in antrum and corpus
      improved significantly (both P < .05 for all timepoints) only in the H. pylori
      eradicated group in comparison with that at baseline. Significant difference in
      intestinal metaplasia between H. pylori-eradicated and H. pylori-negative groups
      disappeared from >=5 years of follow-up in the antrum and from 3 years of follow
      up in the corpus. CONCLUSION: H. pylori eradication may be a preventative
      strategy for intestinal-type gastric cancer by regression of atrophic gastritis
      and intestinal metaplasia.

PMID- 29193218
TI  - Combined influence of oxygenation and salinity on aggregation kinetics of the
      silver reference nanomaterial NM-300K.
AB  - The combined influence of oxygenation and salinity on agglomeration and/or
      aggregation kinetics of the silver (Ag) nanomaterial NM-300K was investigated,
      and the relationship between its physicochemical fate and toxicity toward an
      estuarine bivalve was established. The results showed that the presence of NaCl
      under certain oxygen conditions (8.5 ppm) promoted the formation of AgCl
      aggregates that could be linked to toxicity effects on aquatic organisms. Environ
      Toxicol Chem 2018;37:1007-1013. (c) 2017 SETAC.

PMID- 29193220
TI  - Keith Lindsey.

PMID- 29193219
TI  - Therapeutic leukocytapheresis in infants and children with leukemia and
      hyperleukocytosis: A single institution experience.
AB  - BACKGROUND: Hyperleukocytosis, defined as white blood cell (WBC) count above 100
      * 109 /L, has high early morbidity and mortality from leukostasis-related
      complications, namely intracranial hemorrhage and pulmonary distress. Initiating
      chemotherapy without prior leukocytoreduction may lead to tumor lysis syndrome
      (TLS). Therapeutic leukocytapheresis (TL) is used as one leukocytoreductive
      intervention; however, its safety and efficacy in pediatric leukemia has not been
      established. The purpose of this study is to evaluate safety of TL in pediatric
      patients and assess the efficacy of TL in reducing WBC count in pediatric
      leukemia. METHODS: Retrospective chart review was conducted on 14 patients with
      acute lymphoblastic leukemia (ALL) and 5 with acute myeloid leukemia (AML) who
      underwent TL during the period 2000-2014 at a single institution. RESULTS: Mean
      WBC count of 19 patients who received TL was 483.2 * 109 /L (547.1 in ALL, 304.3
      in AML); a portion of patients presented with central nervous system symptoms
      (15%), respiratory symptoms (10%), or both (10%). TL reduced WBC count (mean
      50.7% reduction after a single TL procedure; additional 17.1% reduction after a
      second TL procedure in 6 patients). Short-term survival immediately following TL
      was 100% without any major procedural complication. Mean survival time in
      patients with AML was 1.5 years and with ALL was 6.5 years. CONCLUSIONS: TL
      significantly reduces WBC number in pediatric leukemia patients as young as 22
      days old. In our retrospective study, TL was not associated with any significant
      complications and suggests that TL is a safe initial procedure in pediatric
      leukemia.

PMID- 29193221
TI  - Ectomycorrhizal fungi and the enzymatic liberation of nitrogen from soil organic
      matter: why evolutionary history matters.
AB  - Contents Summary 68 I. Introduction 68 II. Have ECM fungi retained genes with
      lignocellulolytic potential from saprotrophic ancestors? 69 III. Are genes with
      saprotrophic function expressed by ECM fungi when in symbiosis? 71 IV. Do
      transcribed enzymes operate to obtain N from SOM? 71 V. Is the organic N derived
      from SOM transferred to the plant host? 71 VI. Concluding remarks 72
      Acknowledgements 72 References 72 SUMMARY: The view that ectomycorrhizal (ECM)
      fungi commonly participate in the enzymatic liberation of nitrogen (N) from soil
      organic matter (SOM) has recently been invoked as a key mechanism governing the
      biogeochemical cycles of forest ecosystems. Here, we provide evidence that not
      all evolutionary lineages of ECM have retained the genetic potential to produce
      extracellular enzymes that degrade SOM, calling into question the ubiquity of the
      proposed mechanism. Further, we discuss several untested conditions that must be
      empirically validated before it is certain that any lineage of ECM fungi actively
      expresses extracellular enzymes in order to degrade SOM and transfer N contained
      therein to its host plant.

PMID- 29193222
TI  - A convergent outcome: small genomes in mangroves.

PMID- 29193223
TI  - Sharing resources for mutual benefit: crosstalk between disciplines deepens the
      understanding of mycorrhizal symbioses across scales.

PMID- 29193224
TI  - Fresh knowledge for an old relationship: new discoveries in molecular mycorrhizal
      research.

PMID- 29193225
TI  - Biological significance of TERT promoter mutation in papillary urothelial
      neoplasm of low malignant potential.
AB  - AIMS: Mutations in FGFR3 and the promoter region of the telomerase reverse
      transcriptase (TERT) gene have been found frequently in urothelial carcinoma of
      the urinary bladder. However, related data for papillary urothelial neoplasm of
      low malignant potential (PUNLMP) are limited. In this study, we investigated the
      mutation status of the TERT promoter, FGFR3 and HRAS in low-grade papillary
      urothelial neoplasms and evaluated their prognostic significance. METHODS AND
      RESULTS: The cases included in this study comprised 21 inverted papillomas, 30
      PUNLMPs and 34 low-grade non-invasive papillary urothelial carcinomas (NIPUCs).
      TERT promoter mutations were observed in 10 (33%) PUNLMPs and 17 (50%) low-grade
      NIPUCs, but not in any inverted papilloma. FGFR3 mutations were observed more
      frequently in PUNLMP and low-grade NIPUC than in inverted papillomas (P = 0.009),
      whereas the opposite trend was noted for HRAS mutations (P < 0.001). Regarding
      the clinical outcome, TERT promoter mutation was associated with a higher
      recurrence rate in PUNLMP (P = 0.024) but not in low-grade NIPUC (P = 0.530).
      Notably, PUNLMP cases with TERT promoter mutations had a similar recurrence rate
      to that in low-grade NIPUC cases (P = 0.487). CONCLUSIONS: Our results suggest
      that the status of the TERT promoter mutation may serve as a biomarker of
      prognostic stratification in patients with PUNLMP.

PMID- 29193226
TI  - Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of
      chronic hepatitis C: real-world results from 18 378 patients in Egypt.
AB  - BACKGROUND: Treatment of chronic hepatitis C using combination of sofosbuvir
      (SOF) and daclatasvir (DCV) was used in several clinical trials and multicentre
      studies, which were somewhat limited to genotypes 1-3. The national program in
      Egypt is using SOF-DCV combination for large scale treatment. AIM: To assess the
      efficacy and safety of combined SOF-DCV in treating patients with HCV-G4 in a
      real-world setting. METHODS: Data and outcome of chronic HCV patients who were
      treated for 12 weeks with generic medications: DCV 60 mg plus SOF 400 mg +/-
      ribavirin (RBV) within the national hepatitis C treatment program in Egypt are
      presented. Treatment-naive patients without cirrhosis were treated without RBV,
      and those who had cirrhosis or were treatment-experienced (interferon experienced
      or SOF experienced) received RBV. Efficacy and safety were assessed, and baseline
      factors associated with sustained virological response at post-treatment week 12
      (SVR12) were explored. RESULTS: During the first 2 months of the programme, 18
      378 patients with HCV-G4 started treatment with SOF-DCV with or without RBV.
      Overall, 95.1% achieved SVR12 (95.4% among patients treated without RBV and 94.7%
      for patients treated with RBV, P = .32). Treatment was prematurely discontinued
      in only 1.5% of patients. The most common events leading to discontinuation were
      patient withdrawal (n = 76) and pregnancy (n = 5). Five deaths occurred within
      this group. CONCLUSIONS: Real-world experience of generic SOF-DCV in patients
      with chronic HCV-G4 proved to be safe and associated with a high SVR12 rate, in
      patients with different stages of fibrosis.

PMID- 29193227
TI  - Minimally invasive lag screw fixation of sacroiliac luxation/fracture using a
      dedicated novel instrument system: Apparatus and technique description.
AB  - OBJECTIVE: To describe a novel Sacroiliac Luxation Instrument System (SILISTM)
      and its application in minimally invasive osteosynthesis (MIO) of sacroiliac
      luxations/fractures (SIL/F). The SILIS was designed to provide stable SIL/F
      reduction and accurate sacral screw placement while reducing personnel exposure
      to ionizing radiation during intraoperative fluoroscopy. STUDY DESIGN:
      Descriptive, proof of concept cadaveric study. METHODS: A right SIL and a left
      SIL/F were created on a Labrador Retriever that had died of natural causes.
      Bilateral sacroiliac lag screw fixation was performed under fluoroscopic guidance
      with the SILIS, which consists of dedicated reduction and fixation instruments
      rigidly linked to table-bound 6-axis arms. RESULTS: Throughout surgery, the SILIS
      facilitated and maintained stable reduction and allowed accurate placement of a
      custom designed drill guide over the sacral body without the surgeon's manual
      holding of any reduction or fixation instruments. The surgical team was therefore
      able to step away from the C-arm when acquiring fluoroscopic images, thus
      reducing exposure to radiation. Dorsoventral and craniocaudal screw deviation
      from an ideal trajectory ranged from 0.9 degrees  to 3.8 degrees . Both screws
      were fully located within the sacral body. CONCLUSION: The SILIS addresses
      limitations associated with MIO of SIL/F, including maintenance of reduction
      throughout surgery along with reliable and accurate sacral screw placement.
      Distance from the X-ray source is the most effective protection against
      radiation. Use of the SILIS allows the surgical team to move away from the C-arm
      during fluoroscopy, thereby reducing personnel exposure to dangerous direct and
      back-scattered ionizing radiation.

PMID- 29193228
TI  - Adding neonatal hyperbilirubinemia/bilirubin encephalopathy to the American
      Society for Apheresis Guidelines on Therapeutic Apheresis.

PMID- 29193229
TI  - Identification of microRNAs and genes associated with hyperandrogenism in the
      follicular fluid of women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease,
      which is characterized by hyperandrogenism (HA), chronic anovulation, polycystic
      ovaries, insulin resistance, and obesity. At present, the mechanism by which
      PCOS/HA occurs has not been fully elucidated, thus, the mechanisms behind and
      interventions for HA in PCOS are current hot topics in research. MiRNAs have
      recently been shown to serve as diagnostic or prognostic biomarkers in patients
      with cancer. Thus, we are currently focused on studying the altered expression of
      miRNAs in follicular fluid and their correlation with HA in PCOS. Illumina deep
      sequencing technology was used to explore different miRNAs in the follicular
      fluid of women with PCOS/HA and in the follicular fluid of women in a control
      group. Target prediction databases were then used to analyse the target genes of
      different expressed miRNAs, and GO analysis and the KEGG pathway database were
      used to identify the functions and the main biochemical and signalling pathways
      of differentially expressed target genes. The expression levels of 263 miRNAs
      were significantly different (>2-fold up-regulated or <0.5-fold down-regulated, P
      < 0.05) between the two groups of women. For example, the expression levels of
      miRNA (200a-3p, 10b-3p, 200b-3p, 29c-3p, 99a-3p, and 125a-5p) were significantly
      increased, while there was a decreased expression of miR-105-3p in PCOS patients
      with respect to the control. Literature has shown that the above seven miRNAs
      were associated with HA in PCOS. Furthermore, 31 770 genes were predicted to be
      targets of the 263 differentially expressed microRNAs. GO analysis and the KEGG
      pathway database showed involvement of these target genes in HA in PCOS. These
      results suggest the presence of differentially expressed miRNAs in the follicular
      fluid of women with PCOS/HA versus women in the control group. The potential role
      of these microRNAs was elucidated using bioinformatics tools and was found to be
      involved in the regulation of different pathways, biological functions, and
      cellular components underlying PCOS. The results of this research may reveal new
      mechanisms of PCOS/HA and suggest potential treatment targets.

PMID- 29193230
TI  - Deep Infiltrating Endometriosis: Comparison Between 2-Dimensional Ultrasonography
      (US), 3-Dimensional US, and Magnetic Resonance Imaging.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of 2-dimensional (2D) and 3
      dimensional (3D) transvaginal ultrasonography (US) in comparison with magnetic
      resonance imaging (MRI) for identification of deep infiltrating endometriosis.
      METHODS: In this prospective observational study, 159 premenopausal women who
      underwent surgery for a clinical suspicion of deep infiltrating endometriosis
      were prospectively enrolled. All women underwent 2DUS, 3DUS, and MRI. The
      following 3 locations of deep endometriosis were considered: (1) intestinal; (2)
      other posterior lesions (retrocervical septum, rectovaginal septum, uterosacral
      ligaments, and vaginal fornix); and (3) anterior. The sensitivity, specificity,
      positive predictive value, and negative predictive value of 2D and 3D
      transvaginal US in comparison with MRI were determined. RESULTS: Intestinal deep
      infiltrating endometriosis was identified by 2DUS in 56 of 66 patients, by 3DUS
      in 59 of 66, and by MRI in 61 of 66. A receiver operating characteristic curve
      analysis showed optimal results for 2DUS, 3DUS, and MRI (areas under the curve,
      0.86, 0.915, and 0.935, respectively) with a statistically significant difference
      between 2DUS and MRI (P = .0103), even when the 95% confidence interval showed an
      overlap. Other posterior deep infiltrating endometriosis was identified by 2DUS
      in 55 of 75 patients, by 3DUS in 65 of 75, and by MRI in 66 of 75. A receiver
      operating characteristic curve analysis showed very good results for 2DUS, 3DUS,
      and MRI (areas under the curve, 0.801, 0.838, and 0.857) with no statistically
      significant differences. In the 12 women with deep infiltrating endometriosis in
      the anterior location, the nodules were correctly identified by 2DUS in 3 of 12
      patients, by 3DUS in 5 of 12, and by MRI in 6 of 12. CONCLUSIONS: Our results
      seem to suggest that there is a statistically significant difference between 2DUS
      and MRI for the intestinal location of deep infiltrating endometriosis, whereas
      no differences were found among the techniques for the other locations.

PMID- 29193231
TI  - Using MRI cell tracking to monitor immune cell recruitment in response to a
      peptide-based cancer vaccine.
AB  - PURPOSE: MRI cell tracking can be used to monitor immune cells involved in the
      immunotherapy response, providing insight into the mechanism of action, temporal
      progression of tumor growth, and individual potency of therapies. To evaluate
      whether MRI could be used to track immune cell populations in response to
      immunotherapy, CD8+ cytotoxic T cells, CD4+ CD25+ FoxP3+ regulatory T cells, and
      myeloid-derived suppressor cells were labeled with superparamagnetic iron oxide
      particles. METHODS: Superparamagnetic iron oxide-labeled cells were injected into
      mice (one cell type/mouse) implanted with a human papillomavirus-based cervical
      cancer model. Half of these mice were also vaccinated with DepoVaxTM
      (ImmunoVaccine, Inc., Halifax, Nova Scotia, Canada), a lipid-based vaccine
      platform that was developed to enhance the potency of peptide-based vaccines.
      RESULTS: MRI visualization of CD8+ cytotoxic T cells, regulatory T cells, and
      myeloid-derived suppressor cells was apparent 24 h post-injection, with
      hypointensities due to iron-labeled cells clearing approximately 72 h post
      injection. Vaccination resulted in increased recruitment of CD8+ cytotoxic T
      cells, and decreased recruitment of myeloid-derived suppressor cells and
      regulatory T cells to the tumor. We also found that myeloid-derived suppressor
      cell and regulatory T cell recruitment were positively correlated with final
      tumor volume. CONCLUSION: This type of analysis can be used to noninvasively
      study changes in immune cell recruitment in individual mice over time,
      potentially allowing improved application and combination of immunotherapies.
      Magn Reson Med 80:304-316, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 29193232
TI  - Adding neonatal hyperbilirubinemia/bilirubin encephalopathy to the American
      Society for Apheresis Guidelines on Therapeutic Apheresis.

PMID- 29193233
TI  - Development and validation of an LC-MS/MS method for the determination of a novel
      thienoquinolin urea transporter inhibitor PU-48 in rat plasma and its application
      to a pharmacokinetic study.
AB  - A specific, sensitive and stable high-performance liquid chromatographic-tandem
      mass spectrometry (LC-MS/MS) method was developed and validated for the
      quantitative determination of methyl 3-amino-6-methoxythieno [2,3-b]quinoline-2
      carboxylate (PU-48), a novel diuretic thienoquinolin urea transporter inhibitor
      in rat plasma. In this method, the chromatographic separation of PU-48 was
      achieved with a reversed-phase C18 column (100 * 2.1 mm, 3 MUm) at 35 degrees C.
      The mobile phase consisted of acetonitrile and water with 0.05% formic acid added
      with a gradient elution at flow rate of 0.3 mL/min. Samples were detected with
      the triple-quadrupole tandem mass spectrometer with multiple reaction monitoring
      mode via electrospray ionization source in positive mode. The retention time were
      6.2 min for PU-48 and 7.2 min for megestrol acetate (internal standard, IS). The
      monitored ion transitions were mass-to-charge ratio (m/z) 289.1 -> 229.2 for PU
      48 and m/z 385.3 -> 267.1 for the internal standard. The calibration curve for PU
      48 was linear over the concentration range of 0.1-1000 ng/mL (r2 > 0.99), and the
      lower limit of quantitation was 0.1 ng/mL. The precision, accuracy and stability
      of the method were validated adequately. The developed and validated method was
      successfully applied to the pharmacokinetic study of PU-48 in rats.

PMID- 29193234
TI  - Dexmedetomidine as an adjuvant to 0.5% ropivacaine in ultrasound-guided axillary
      brachial plexus block.
AB  - WHAT IS KNOWN AND OBJECTIVE: The aim of this study was to elucidate the effect of
      dexmedetomidine added to ropivacaine on the onset and duration of sensory and
      motor block and duration of analgesia of ultrasound-guided axillary brachial
      plexus block. METHODS: Thirty-seven ASA physical status I-II patients with
      elective forearm and hand surgery under ultrasound-guided axillary brachial
      plexus block were randomly divided into 2 groups. Patients in ropivacaine
      dexmedetomidine group (group RD, n = 19) received 15 mL of 0.5% ropivacaine with
      100 MUg (1 mL) dexmedetomidine, and patients in ropivacaine group (group R, n =
      18) received 15 mL of 0.5% ropivacaine with 1 mL of normal saline. Onset time and
      duration of sensory and motor block and duration of analgesia were assessed.
      RESULTS AND DISCUSSION: Duration of sensory block (U-value = 35, P < .001),
      duration of motor block (P = .001) and duration of analgesia (P < .001) were
      extended in group RD compared to group R. Onset time of sensory block in group RD
      was significantly faster than in group R (U-value = 65.5, P = .001). Onset time
      of motor block showed no significant difference between the 2 groups (U-value =
      116.5, P = .096). Adverse reactions were reported only in group RD (bradycardia
      in 2 and hypotension in 3 patients). WHAT IS NEW AND CONCLUSION: Our study
      indicated that dexmedetomidine 100 MUg as adjuvant on ultrasound-guided axillary
      plexus block significantly prolonged the duration of sensory block and analgesia,
      as well as accelerated the time to onset of sensory block. These results should
      be weighed against the increased risks of motor block prolongation, transient
      bradycardia and hypotension and allow for attentive optimism, only if prolonged
      clinical trials provide a definitive answer.

PMID- 29193235
TI  - Prospective aquatic risk assessment for chemical mixtures in agricultural
      landscapes.
AB  - Environmental risk assessment of chemical mixtures is challenging because of the
      multitude of possible combinations that may occur. Aquatic risk from chemical
      mixtures in an agricultural landscape was evaluated prospectively in 2 exposure
      scenario case studies: at field scale for a program of 13 plant-protection
      products applied annually for 20 yr and at a watershed scale for a mixed land-use
      scenario over 30 yr with 12 plant-protection products and 2 veterinary
      pharmaceuticals used for beef cattle. Risk quotients were calculated from
      regulatory exposure models with typical real-world use patterns and regulatory
      acceptable concentrations for individual chemicals. The results could
      differentiate situations when there was concern associated with single chemicals
      from those when concern was associated with a mixture (based on concentration
      addition) with no single chemical triggering concern. Potential mixture risk was
      identified on 0.02 to 7.07% of the total days modeled, depending on the scenario,
      the taxa, and whether considering acute or chronic risk. Taxa at risk were
      influenced by receiving water body characteristics along with chemical use
      profiles and associated properties. The present study demonstrates that a
      scenario-based approach can be used to determine whether mixtures of chemicals
      pose risks over and above any identified using existing approaches for single
      chemicals, how often and to what magnitude, and ultimately which mixtures (and
      dominant chemicals) cause greatest concern. Environ Toxicol Chem 2018;37:674-689.
      (c) 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley
      Periodicals, Inc. on behalf of SETAC.

PMID- 29193236
TI  - Inhibitory effect of naringenin via IL-13 level regulation on thymic stromal
      lymphopoietin-induced inflammatory reactions.
AB  - Naringenin (NG) has various beneficial properties, such as anti-cancer and anti
      inflammatory effects. Thymic stromal lymphopoietin (TSLP) induces mast cell
      proliferation and inflammatory reactions. The aim of this study was to
      investigate the regulatory effect of NG on TSLP-induced mast cell proliferation
      and inflammatory reactions using human mast cell line (HMC-1) cells. HMC-1 cells
      were pre-treated with NG and then treated with TSLP. HMC-1 cells proliferation
      was determined by quantifying bromodeoxyuridine incorporation. Levels of anti
      apoptotic and pro-apoptotic factors were analyzed by western blot analysis. The
      productions and mRNA expressions of interleukin (IL)-13 and tumour necrosis
      factor-alpha (TNF-alpha) were analyzed by ELISA and quantitative real-time PCR.
      We found that NG significantly attenuated HMC-1 cells proliferation and Ki-67
      mRNA expression promoted by TSLP. NG significantly suppressed mRNA expression of
      TSLP receptor and IL-7 receptor alpha in TSLP-treated HMC-1 cells. NG
      significantly down-regulated levels of phosphorylated-signal transducer and
      activation of transcription 6 and murine double-minute 2 in TSLP-treated HMC-1
      cells, up-regulated levels of cleaved poly ADP-ribose polymerase and p53 in TSLP
      treated HMC-1 cells. Furthermore, NG significantly decreased the productions and
      mRNA expressions of IL-13 and TNF-alpha in TSLP-treated HMC-1 cells. These
      results suggest NG has an inhibitory effect on mast cell-mediated allergic
      inflammatory reactions.

PMID- 29193237
TI  - Cloning and analysis of peptidoglycan recognition protein-LC and immune
      deficiency from the diamondback moth, Plutella xylostella.
AB  - Peptidoglycan (PGN) exists in both Gram-negative and Gram-positive bacteria as a
      component of the cell wall. PGN is an important target to be recognized by the
      innate immune system of animals. PGN recognition proteins (PGRP) are responsible
      for recognizing PGNs. In Drosophila melanogaster, PGRP-LC and IMD (immune
      deficiency) are critical for activating the Imd pathway. Here, we report the
      cloning and analysis of PGRP-LC and IMD (PxPGRP-LC and PxIMD) from diamondback
      moth, Plutella xylostella (L.), the insect pest of cruciferous vegetables. PxPGRP
      LC gene consists of six exons encoding a polypeptide of 308 amino acid residues
      with a transmembrane region and a PGRP domain. PxIMD cDNA encodes a polypeptide
      of 251 amino acid residues with a death domain. Sequence comparisons indicate
      that they are characteristic of Drosophila PGRP-LC and IMD homologs. PxPGRP-LC
      and PxIMD were expressed in various tissues and developmental stages. Their mRNA
      levels were affected by bacterial challenges. The PGRP domain of PxPGRP-LC lacks
      key residues for the amidase activity, but it can recognize two types of PGNs.
      Overexpression of full-length and deletion mutants in Drosophila S2 cells induced
      expression of some antimicrobial peptide genes. These results indicate that
      PxPGRP-LC and PxIMD may be involved in the immune signaling of P. xylostella.
      This study provides a foundation for further studies of the immune system of P.
      xylostella.

PMID- 29193238
TI  - Experiences of living with a sexually transmitted disease: an integrative review.
AB  - PURPOSE: This integrative review describes experiences related to living with a
      sexually transmitted disease (STD). DESIGN: The data search was conducted using
      the CINAHL, MEDLINE (Ovid), PsycINFO and PubMed databases between the years 2000
      and 2016. A manual search was also used. The retrieved data consisted of 33
      original articles which were analysed using deductive and inductive content
      analysis. RESULTS: Based on the results, an infected person has a need for
      information about STDs and experiences emotions such as a loss of purity and
      control over his/her body. In addition, the ego of the infected person is wounded
      due to the infection. Concerns about the results of treatments, suffering side
      effects, and experiences of unprofessional behaviour by nursing staff are related
      to the treatment of an STD. Having an STD in everyday life means coping with a
      changing condition, but there are resources that can provide support. The quality
      of life can also be negatively affected by an STD, and a future with an STD can
      manifest different hopes and concerns. In relation to other people, an STD has a
      marked effect, especially concerning sexual relations. The person's sex life can
      fade away; however, it may remain as an enjoyable experience. The infected person
      may also adopt safer sexual behaviours or continue with a risk-taking behaviour.
      CONCLUSION: The results of this review can be used in the development of nursing
      practices, as well as be used in the prevention of STDs.

PMID- 29193239
TI  - Calibration of silicone rubber rods as passive samplers for pesticides at two
      different flow velocities: Modeling of sampling rates under water boundary layer
      and polymer control.
AB  - There is a need to determine time-weighted average concentrations of polar
      contaminants such as pesticides by passive sampling in environmental waters.
      Calibration data for silicone rubber-based passive samplers are lacking for this
      class of compounds. The calibration data, sampling rate (Rs ), and partition
      coefficient between silicone rubber and water (Ksw ) were precisely determined
      for 23 pesticides and 13 candidate performance reference compounds (PRCs) in a
      laboratory calibration system over 14 d for 2 water flow velocities, 5 and 20 cm
      s-1 . The results showed that an in situ exposure duration of 7 d left a silicone
      rubber rod passive sampler configuration in the linear or curvilinear uptake
      period for 19 of the pesticides studied. A change in the transport mechanism from
      polymer control to water boundary layer control was observed for pesticides with
      a log Ksw of approximately 3.3. The PRC candidates were not fully relevant to
      correct the impact of water flow velocity on Rs . We therefore propose an
      alternative method based on an overall resistance to mass transfer model to
      adjust Rs from laboratory experiments to in situ hydrodynamic conditions. We
      estimated diffusion coefficients (Ds ) and thickness of water boundary layer
      (deltaw ) as adjustable model parameters. Log Ds values ranged from -12.13 to 
      10.07 m2  s-1 . The estimated deltaw value showed a power function correlation
      with water flow velocity. Environ Toxicol Chem 2018;37:1208-1218. (c) 2017 SETAC.

PMID- 29193240
TI  - Intracranial fetus-in-fetu with numerous fully developed organs.
AB  - Fetus in fetu (FIF) is an extremely rare anomaly featuring a monozygotic,
      diamniotic, parasitic twin, enclosed within its host twin. It is characterized by
      the presence of vertebrae and well-developed organs in a fetiform mass. Only 18
      cases of intracranial FIF have been published. Of them, only five cases were
      prenatally detected. This study prenatally demonstrated triplet FIFs at 31 weeks
      within amniotic-like sac in the fetal skull, consisting of multiple well-defined
      organs. The FIF attached to the host twin via body stalk containing a single main
      feeding artery and vein, representing umbilical vessels. Surgical removal was
      performed at the age of two months. Pathological examination showed the triplet
      FIF, consisting of numerous well-developed organs (musculocutaneous-skeletal,
      nervous, respiratory, gastrointestinal systems etc.), with soft tissue/skin
      coverings, but no vertebral body was seen. Molecular genetic analysis revealed
      identical genetic mapping among the three FIFs and the host. This case provides
      strong evidence against Willis's hypothesis but supports Spencer's theory of
      abnormal twinning.

PMID- 29193241
TI  - Does informal caregiving affect self-esteem? Results from a population-based
      study of individuals aged 40 and over in Germany from 2002 to 2014.
AB  - BACKGROUND: While it is known that informal caregiving is associated with care
      derived self-esteem cross-sectionally, little is known about the impact of
      informal caregiving on general self-esteem longitudinally. Thus, we aimed at
      examining whether informal caregiving affects general self-esteem using a
      longitudinal approach. METHODS: Data were gathered from a population-based sample
      of community-dwelling individuals aged 40 and over in Germany from 2002 to 2014
      (n = 21 271). General self-esteem was quantified using the Rosenberg scale.
      Individuals were asked whether they provide informal care regularly. RESULTS:
      Fixed effects regressions showed no significant effect of informal caregiving on
      general self-esteem longitudinally. General self-esteem decreased with increasing
      morbidity, increasing age, decreasing social ties, whereas it was not associated
      with changes in employment status, marital status and body mass index. Additional
      models showed that decreases in self-esteem were associated with decreases in
      functional health and increases in depressive symptoms. CONCLUSION: Our
      longitudinal study emphasises that the occurrence of informal caregiving did not
      affect general self-esteem longitudinally. Further research is needed in other
      cultural settings using panel data methods.

PMID- 29193242
TI  - A peer learning intervention targeting newly graduated nurses: A feasibility
      study with a descriptive design based on the Medical Research Council framework.
AB  - AIMS: The aim of this study was to describe the feasibility of a peer learning
      intervention targeting newly graduated nurses. Feasibility was tested concerning
      consistency of the theoretical description of peer learning with empirical
      findings in a new context, compliance and acceptability, as well as usability of
      a questionnaire measuring the intended future outcome variables. BACKGROUND:
      Newly graduated nurses who meet, socialize and share experiences have described
      supporting each other's ability to cope with stress. Peer learning involves
      individuals in a similar situation learning from and with each other through
      interaction. When implementing new interventions, feasibility studies are used to
      minimize problems in future evaluation studies. DESIGN: Quasi-experimental design
      with an intervention group, followed over time using descriptive methods. The
      study was based on the Medical Research Council framework. METHODS: Repeated semi
      structured interviews, a checklist for fidelity and a questionnaire were
      conducted with 10 newly graduated nurses from January to March 2015. The
      intervention's main component included pairs of newly graduated nurses working
      the same shift and having joint responsibility for a group of patients for a
      period of 3 weeks. The intervention also included 3 months of regular reflection
      by the pair. FINDINGS: Using deductive analysis, the peer learning intervention
      was found to be consistent with the theoretical description. Due to the
      compliance and acceptability, there were lessons learnt. The tested questionnaire
      was found to be useful. CONCLUSIONS: This peer learning intervention seems to be
      feasible in this context. This study will serve as the basis for a future full
      scale evaluation study.

PMID- 29193243
TI  - Dioxin-like contaminants are no longer a risk to the American eel (Anguilla
      rostrata) in Lake Ontario.
AB  - The embryotoxicity of extracts of American eels (Anguilla rostrata) was measured
      to determine whether maternally derived contaminants contribute to the declining
      recruitment of eels to Lake Ontario. Sexually maturing, large yellow and silver
      eels were sampled in 2007 and 2008 from 5 locations in eastern Canada, including
      Lake Ontario; positive controls included eels from the Hudson River, United
      States, and Canal Dessel-Schoten, Belgium (European eel, Anguilla anguilla).
      Japanese medaka eggs were injected immediately after fertilization with 1 or 10
      nL of eel extract and, after 12 d, scored for signs of toxicity. Eel extracts did
      not cause dioxin-like embryotoxicity, reflecting the low concentrations of total
      dioxin equivalents measured chemically in these same extracts. Embryo mortality
      and reduced hatching success at high doses of eel extracts may reflect the
      bioaccumulation of legacy or emerging chemicals of concern. The results were
      consistent with long-term trends of declining concentrations of persistent
      organic pollutants (POPs) in tissues of eels and other fish species from Lake
      Ontario, trends of declining embryotoxicity of eel tissue extracts, and recent
      increases of recruitment of juvenile eels to Lake Ontario. If dioxin-like
      compounds contributed in the past to the decline of recruitment and abundance of
      American eels in Lake Ontario, these data suggest that recruitment should
      recover, following the same trends as the recovery of lake trout reproduction in
      Lake Ontario. Environ Toxicol Chem 2018;37:1061-1070. (c) 2017 SETAC.

PMID- 29193244
TI  - An efficient sequence for fetal brain imaging at 3T with enhanced T1 contrast and
      motion robustness.
AB  - PURPOSE: Ultrafast single-shot T2 -weighted images are common practice in fetal
      MR exams. However, there is limited experience with fetal T1 -weighted
      acquisitions. This study aims at establishing a robust framework that allows
      fetal T1 -weighted scans to be routinely acquired in utero at 3T. METHODS: A 2D
      gradient echo sequence with an adiabatic inversion was optimized to be robust to
      fetal motion and maternal breathing optimizing grey/white matter contrast at the
      same time. This was combined with slice to volume registration and super
      resolution methods to produce volumetric reconstructions. The sequence was tested
      on 22 fetuses. RESULTS: Optimized grey/white matter contrast and robustness to
      fetal motion and maternal breathing were achieved. Signal from cerebrospinal
      fluid (CSF) and amniotic fluid was nulled and 0.75 mm isotropic anatomical
      reconstructions of the fetal brain were obtained using slice-to-volume
      registration and super resolution techniques. Total acquisition time for a single
      stack was 56 s, all acquired during free breathing. Enhanced sensitivity to
      normal anatomy and pathology with respect to established methods is demonstrated.
      A direct comparison with a 3D spoiled gradient echo sequence and a controlled
      motion experiment run on an adult volunteer are also shown. CONCLUSION: This
      paper describes a robust framework to perform T1 -weighted acquisitions and
      reconstructions of the fetal brain in utero. Magn Reson Med 80:137-146, 2018. (c)
      2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals,
      Inc. on behalf of International Society for Magnetic Resonance in Medicine. 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- 29193245
TI  - Review article: gastro-oesophageal reflux disease in asthma and chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: When gastro-oesophageal reflux is causing symptoms or lesions in the
      oesophagus, this is referred to as gastro-oesophageal reflux disease (GERD). GERD
      can manifest itself through typical symptoms (heartburn, regurgitation) or may
      lead to extra-oesophageal symptoms. Extra-oesophageal manifestations of GERD
      gained increasing attention over the last decade, especially respiratory
      disorders, because of the prevalent co-occurrence with GERD. The role of GERD in
      the pathogenesis of respiratory disorders has become a topic of intense
      discussion. AIM: To provide an overview of the current knowledge on the role of
      GERD in asthma and chronic obstructive pulmonary disease (COPD). METHODS: PubMed
      was searched for relevant articles using the keywords: GERD, asthma, COPD,
      prevalence, treatment. Case reports were excluded, only English language articles
      were considered. RESULTS: Estimates for the prevalence of GERD in asthma range
      from 30% to 90%, compared to an average of 24% in controls. In COPD patients, the
      prevalence of GERD ranges from 19% to 78% compared to an average of 18% in
      controls. These data indicate an increased prevalence of GERD in patients with
      asthma and COPD, although causality is not established and GERD treatment yielded
      inconsistent effects. Literature supports GERD as a risk factor for COPD
      exacerbations and a predictor of the 'frequent-exacerbator'-phenotype.
      CONCLUSIONS: Despite the high prevalence of GERD in asthma and COPD, a causal
      link is lacking. The results of anti-reflux therapy on pulmonary outcome are
      inconsistent and contradictory. Future studies will need to identify subgroups of
      asthmatics and COPD patients that may benefit from anti-reflux therapy (nocturnal
      or silent reflux).

PMID- 29193246
TI  - Transcutaneous carbon dioxide application with hydrogel prevents muscle atrophy
      in a rat sciatic nerve crush model.
AB  - : The acceleration of nerve regeneration remains a clinical challenge. We
      previously demonstrated that transcutaneous CO2 application using a novel
      hydrogel increases the oxygen concentration in local tissue via an "artificial
      Bohr effect" with the potential to prevent muscle atrophy. In this study, we
      investigated the effect of transcutaneous CO2 administration on limb function
      after peripheral nerve injury in a rat sciatic nerve injury model. In total, 73
      Sprague-Dawley rats were divided into a sham group, a control group (crush injury
      to sciatic nerve and no treatment) or a CO2 group (crush injury with
      transcutaneous CO2 application). CO2 was administered percutaneously for 20 min
      five times per week. Scores for the sciatic function index and pinprick test were
      significantly higher in the CO2 group than control group. The muscle wet weight
      ratios of the tibialis anterior and soleus muscles were higher in the CO2 group
      than control group. Electrophysiological examination showed that the CO2 group
      had higher compound motor action potential amplitudes and shorter distal motor
      latency than the control group. Histological examination of the soleus muscle
      sections at postoperative week 2 showed shorter fiber diameter in the control
      group than in the CO2 group. The mRNA expression of Atrogin-1 and MuRF-1 was
      lower, mRNA expression of VEGF and myogenin and MyoD was higher in CO2 group at
      postoperative week 2 compared to the control group. CLINICAL SIGNIFICANCE:
      Transcutaneous CO2 application has the therapeutic potential to accelerate the
      recovery of muscle atrophy in peripheral nerve injury. (c) 2017 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1653-1658,
      2018.

PMID- 29193247
TI  - Randomized, Double-Blind, Crossover, Clinical-End-Point Pilot Study to Examine
      the Use of Exhaled Nitric Oxide as a Bioassay for Dose Separation of Inhaled
      Fluticasone Propionate.
AB  - This was a randomized, double-blind, crossover, clinical-end-point pilot study
      examining the hypothesis that inhaled fluticasone propionate decreases exhaled
      nitric oxide (eNO) concentrations within a week of beginning treatment and shows
      evidence of dose separation across the marketed dose range. Subjects had a >=6
      month history of asthma and screening eNO >=60 parts per billion. At the start of
      each treatment period, eNO was >=55 parts per billion, and forced expiratory
      volume in 1 second was >=50% predicted. Subjects attended a clinic visit daily on
      consecutive mornings during each of 3 1-week treatment periods to measure eNO and
      receive once-daily doses of 100/50, 250/50, or 500/50 fluticasone
      propionate/salmeterol combination product (Advair(r) Diskus). Daily eNO value
      recorded was the highest of 3 measurements; 1 inhalation of treatment was then
      administered. Procedures were repeated for 3 treatment cycles, separated by 14
      day minimum washouts. A total of 105 subjects were screened; 22 were randomized;
      and 17 completed all treatments. Mean percentage eNO decrease (standard
      deviation) from day 1 baseline for each treatment period was 36.6 (+/-18.7), 45.3
      (+/-16.5), and 54.6 (+/-12.5) with Advair(r) 100/50, 250/50, and 500/50,
      respectively. Mean percentage decrease in eNO across each treatment (dose) was
      modeled using a mixed-model ANOVA. Although the overall treatment was significant
      (P = .0015), because of the relatively small sample size and within-subject
      variability, only the 100/50 vs 500/50 (P = .0003) and 250/50 vs 500/50 (P =
      .047) treatments were significantly different.

PMID- 29193249
TI  - Turbocharged bilateral pedicled DIEP flap for reconstruction of thigh defect
      without recipient vessels: A case report.
AB  - Reconstruction of thigh defects is usually straightforward, but in cases of poor
      soft tissue quality, free flap reconstruction is not possible due to the absence
      of recipient vessels. The turbocharge technique may increase the viable,
      vascularized area of a flap. In this report we present a case of the use of a
      turbocharged bilateral pedicled DIEP flap for reconstruction of thigh defect
      without recipient vessels. A 29-year-old woman who underwent neoadjuvant
      chemotherapy plus radiation therapy for a leiomyosarcoma on the left thigh. Six
      weeks later, complete tumor excision and a femoropopliteal bypass with
      contralateral saphenous vein was performed. In the following days the wound had
      dehiscence, infection, necrosis of the surrounding muscles and exposure of
      femoropopliteal bypass. No recipient vessels were available for free flap and
      critical limb ischemia due to bypass thrombosis was detected. The reconstruction
      of a large thigh defect (30 * 12 cm) and the coverage of a femoropopliteal bypass
      with a turbocharged bilateral pedicled DIEP flap was performed. A flap including
      the entire infraumbilical tissue was designed and the anastomosis of the proximal
      stump of the right inferior epigastric vessels with the distal ends of the
      inferior left epigastric vessels was performed to increase the viable area. The
      flap survived without any complications during the postoperative period. At 12
      month follow up, coverage was stable with no tumor recurrence. Our result
      suggests that a turbocharged bilateral pedicled DIEP flap may be an option for
      reconstructing large tissue defects when no recipient vessels are available for
      free flap.

PMID- 29193248
TI  - Impact of muscle volume and muscle function decline in patients undergoing
      surgical resection for hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: This study investigated the prognostic impact of muscle
      volume loss (MVL) and muscle function decline in patients undergoing resection
      for hepatocellular carcinoma (HCC). METHODS: This study enrolled 171 naive HCC
      patients treated with resection from 2007 to 2015, after excluding those lacking
      spirometry or computed tomography findings, who had received non-curative
      treatments, or with restrictive or obstructive lung disorders. The median peak
      expiratory flow rate (%PEF) was set as the cut-off value for muscle function
      decline, and MVL was diagnosed using a previously reported value. Clinical
      backgrounds and prognosis were retrospectively evaluated. RESULTS: Overall
      survival rate was lower in the MVL (n = 35) as compared with the non-MVL (n =
      136) group (1/3/5-year overall survival rate = 88.2%/81.6%/55.6% vs
      91.0%/81.5%/74.8%, respectively; P = 0.0083), while there were no differences
      regarding hepatic function or tumor burden between the groups. Child-Pugh class B
      (hazard ratio [HR] 3.510, 95% confidence interval [CI]: 1.558-7.926, P = 0.0025),
      beyond Milan criteria (HR 1.866, 95%CI: 1.024-3.403, P = 0.042), and presence of
      MVL (HR 1.896, 95%CI: 1.052-3.416, P = 0.033) were significant prognostic
      factors. The decreased %PEF group (n = 84) showed a higher rate of postoperative
      delirium than the others (n = 87) (27.4% vs 11.5%, P = 0.0088). The cut-off
      values for %PEF and age for postoperative delirium were 63.3% (area under
      receiver operating characteristic [AUROC] 0.697) and 73 years old (AUROC 0.734),
      respectively. Delirium was observed in 50.0% (14/28) of patients with both
      factors, 23.8% (15/63) of those with 1 factor, and 5.0% (4/80) of those without
      either factor. CONCLUSION: Muscle volume loss is an independent prognostic factor
      in HCC patients treated with surgical resection, while advanced age and decreased
      muscle function might indicate high risk for postoperative delirium.

PMID- 29193250
TI  - Design of universal parallel-transmit refocusing kT -point pulses and application
      to 3D T2 -weighted imaging at 7T.
AB  - PURPOSE: T2 -weighted sequences are particularly sensitive to the radiofrequency
      (RF) field inhomogeneity problem at ultra-high-field because of the errors
      accumulated by the imperfections of the train of refocusing pulses. As parallel
      transmission (pTx) has proved particularly useful to counteract RF
      heterogeneities, universal pulses were recently demonstrated to save precious
      time and computational efforts by skipping B1 calibration and online RF pulse
      tailoring. Here, we report a universal RF pulse design for non-selective
      refocusing pulses to mitigate the RF inhomogeneity problem at 7T in turbo spin
      echo sequences with variable flip angles. METHOD: Average Hamiltonian theory was
      used to synthetize a single non-selective refocusing pulse with pTx while
      optimizing its scaling properties in the presence of static field offsets. The
      design was performed under explicit power and specific absorption rate
      constraints on a database of 10 subjects using a 8Tx-32Rx commercial coil at 7T.
      To validate the proposed design, the RF pulses were tested in simulation and
      applied in vivo on 5 additional test subjects. RESULTS: The root-mean-square
      rotation angle error (RA-NRMSE) evaluation and experimental data demonstrated
      great improvement with the proposed universal pulses (RA-NRMSE ~8%) compared to
      the standard circularly polarized mode of excitation (RA-NRMSE ~26%). CONCLUSION:
      This work further completes the spectrum of 3D universal pulses to mitigate RF
      field inhomogeneity throughout all 3D MRI sequences without any pTx calibration.
      The approach returns a single pulse that can be scaled to match the desired flip
      angle train, thereby increasing the modularity of the proposed plug and play
      approach. Magn Reson Med 80:53-65, 2018. (c) 2017 International Society for
      Magnetic Resonance in Medicine.

PMID- 29193251
TI  - Which patients with gynaecomastia require more detailed investigation?
AB  - Gynaecomastia may be due to medication, chronic liver or kidney disease,
      hypogonadism (primary or secondary to pituitary disease) or hyperthyroidism.
      Having excluded these aetiologies, it is imperative to be vigilant for underlying
      malignancy causing gynaecomastia. These include human chorionic gonadotrophin
      secreting testicular and extratesticular tumours and oestrogen-secreting
      testicular tumours and feminising adrenal tumours.

PMID- 29193252
TI  - Immune function of a Rab-related protein by modulating the JAK-STAT signaling
      pathway in the silkworm, Bombyx mori.
AB  - The Rab-family GTPases mainly regulate intracellular vesicle transport, and play
      important roles in the innate immune response in invertebrates. However, the
      function and signal transduction of Rab proteins in immune reactions remain
      unclear in silkworms. In this study, we analyzed a Rab-related protein of
      silkworm Bombyx mori (BmRABRP) by raising antibodies against its bacterially
      expressed recombinant form. Tissue distribution analysis showed that BmRABRP mRNA
      and protein were high expressed in the Malpighian tubule and fat body,
      respectively. However, among the different stages, only the fourth instar larvae
      and pupae showed significant BmRABRP levels. After challenge with four pathogenic
      microorganisms (Escherichia coli, BmNPV, Beauveria bassiana, Micrococcus luteus),
      the expression of BmRABRP mRNA in the fat body was significantly upregulated. In
      contrast, the BmRABRP protein was significantly upregulated after infection with
      BmNPV, while it was downregulated by E. coli, B. bassiana, and M. luteus. A
      specific dsRNA was used to explore the immune function and relationship between
      BmRABRP and the JAK-STAT signaling pathway. After BmRABRP gene interference,
      significant reduction in the number of nodules and increased mortality suggested
      that BmRABRP plays an important role in silkworm's response to bacterial
      challenge. In addition, four key genes (BmHOP, BmSTAT, BmSOCS2, and BmSOCS6) of
      the JAK-STAT signaling pathway showed significantly altered expressions after
      BmRABRP silencing. BmHOP and BmSOCS6 expressions were significantly decreased,
      while BmSTAT and BmSOCS2 were significantly upregulated. Our results suggested
      that BmRABRP is involved in the innate immune response against pathogenic
      microorganisms through the JAK-STAT signaling pathway in silkworm.

PMID- 29193253
TI  - Clinicians need to decrease antibiotic use in previously healthy infants
      hospitalised with bronchiolitis.

PMID- 29193254
TI  - Obstacles and challenges for tissue engineering and regenerative medicine:
      Australian nuances.
AB  - The clinical need and historical approaches to tissue engineering as applied to
      regenerative medicine are introduced, along with comments on activities in this
      field around Australia, and then the huge advances for tissue culture studies are
      discussed (Part A). Combinations of human stem cells and new approaches for
      generating bioscaffolds present great opportunities for in vitro studies of basic
      biology and physiology, drug testing and high throughput screening for the
      pharmaceutical industry, and the advanced tissue engineering of organs and
      devices. The future here is bright. The major obstacles arise with in vivo
      application of these bioengineering advances using animal models and humans (Part
      B), and the complexity of living tissues and the challenges of increased scale
      required for clinical translation to the large human situation are first
      discussed. While clinical success seen with implantation of acellular
      bioscaffolds (with population by host cells) is likely to expand for human use,
      the major challenge relates to (generally) low survival in vivo of (donor or
      autologous) cells that are expanded and grown in tissue culture before
      implantation into the living body. Another major challenge is revascularisation
      of implanted tissues/organs at the human scale. The innovative approaches and
      rapid advances in tissue bioengineering hold great promise for overcoming these
      major obstacles and extending the clinical applications of these technologies.

PMID- 29193255
TI  - Evaluation of the single medial circummuscular perforator DIEP flap: Outcomes and
      comparison to traditional transmuscular single perforator flap.
AB  - INTRODUCTION: Successful breast reconstruction using deep inferior epigastric
      perforator (DIEP) flaps depends on optimal perforator choice. Circummuscular
      wraparound medial perforators allow for no rectus dissection and minimal fascial
      incisions, often presenting as an ideal option. The aim of our study is to
      evaluate outcomes of the single medial wraparound perforator flap in comparison
      to more traditional transmuscular single-perforator DIEP flaps. PATIENTS AND
      METHODS: A retrospective chart review was conducted of all DIEP flaps performed
      by the senior author from 2011 to 2016, yielding 269 flaps on 157 patients. For
      this study, we included all patients who underwent reconstruction of the
      breast(s) and possessed circummuscular perforators arising from the DIE vessels.
      A control group consisted of all consecutive patients with transmuscular one
      perforator DIEP flaps. Patient details and their postoperative outcomes were
      collected. RESULTS: In our study, eight patients (5.1%) were of the medial
      wraparound variety. Sixteen control patients (10.2%) with similar comorbidities
      had flaps that were of the more traditional single perforator transmuscular
      variety. There was a slight trend toward decreased operative time in the medial
      wraparound group, however, it was not found to be statistically significant (536
      +/- 81 vs. 572 +/- 84 min, P = .377). Complication profiles were similar between
      groups (25.0 vs. 18.8%, P = .722), with no increased rates of fat necrosis in the
      wraparound cohort. CONCLUSION: Based on our findings, using a medial wraparound
      perforator is a safe and reliable option when compared with a single
      transmuscular perforator DIEP flap. Choosing the wraparound perforator may show
      benefit as it eliminates muscular dissection and nerve damage, and tends to
      minimize fascial incision length.

PMID- 29193256
TI  - Post-Traumatic Heterotopic Ossification: An Old Problem in Need of New Solutions.
AB  - Heterotopic ossification (HO) is the formation of pathological bone in ectopic
      sites and it can have serious consequences for functional outcomes. For many
      years, its main clinical relevance was as a rare complication of elective joint
      arthroplasty or CNS injury and a number of prophylaxes were developed to mitigate
      against it in these settings. As a consequence of changes in patterns of wounding
      and survival in conflicts since the turn of the century, post-traumatic HO has
      become much more common and case severity has increased. It represents one of the
      main barriers to rehabilitation in a large cohort of combat-injured patients.
      However, extant prophylaxes have not been shown to be effective or appropriate in
      this patient cohort. In addition, the lack of reliable early detection or means
      of predicting which patients will develop HO is another barrier to effective
      prevention. This review examines the current state of understanding of post
      traumatic HO including the historical context, epidemiology, pathophysiology,
      clinical issues, currently prophylaxis and detection, management, and potential
      future approaches. Our aims are to highlight the current lack of effective means
      of early detection and prevention of HO after major trauma and to stimulate
      research into novel solutions to this challenging problem. (c) 2017 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1061-1068,
      2018.

PMID- 29193257
TI  - Fundamental structural and functional properties of Aquaporin ion channels found
      across the kingdoms of life.
AB  - Aquaporin (AQP) channels in the major intrinsic protein (MIP) family are known to
      facilitate transmembrane water fluxes in prokaryotes and eukaryotes. Some classes
      of AQPs also conduct ions, glycerol, urea, CO2 , nitric oxide, and other small
      solutes. Ion channel activity has been demonstrated for mammalian AQPs 0, 1, 6,
      Drosophila Big Brain (BIB), soybean nodulin 26, and rockcress AtPIP2;1. More
      classes are likely to be discovered. Newly identified blockers are providing
      essential tools for establishing physiological roles of some of the AQP dual
      water and ion channels. For example, the arylsulfonamide AqB011 which selectively
      blocks the central ion pore of mammalian AQP1 has been shown to impair migration
      of HT29 colon cancer cells. Traditional herbal medicines are sources of selective
      AQP1 inhibitors that also slow cancer cell migration. The finding that plant
      AtPIP2;1 expressed in root epidermal cells mediates an ion conductance regulated
      by calcium and protons provided insight into molecular mechanisms of
      environmental stress responses. Expression of lens MIP (AQP0) is essential for
      maintaining the structure, integrity and transparency of the lens, and Drosophila
      BIB contributes to neurogenic signalling pathways to control the developmental
      fate of fly neuroblast cells; however, the ion channel roles remain to be defined
      for MIP and BIB. A broader portfolio of pharmacological agents is needed to
      investigate diverse AQP ion channel functions in situ. Understanding the dual
      water and ion channel roles of AQPs could inform the development of novel agents
      for rational interventions in diverse challenges from agriculture to human
      health.

PMID- 29193258
TI  - Comparative transcriptome analysis provides insights of anti-insect molecular
      mechanism of Cassia obtusifolia trypsin inhibitor against Pieris rapae.
AB  - Pieris rapae, a serious Lepidoptera pest of cultivated crucifers, utilizes midgut
      enzymes to digest food and detoxify secondary metabolites from host plants. A
      recombinant trypsin inhibitor (COTI) from nonhost plant, Cassia obtusifolia,
      significantly decreased activities of trypsin-like proteases in the larval midgut
      on Pieris rapae and could suppress the growth of larvae. In order to know how
      COTI took effect, transcriptional profiles of P. rapae midgut in response to COTI
      was studied. A total of 51,544 unigenes were generated and 45.86% of which had
      homologs in public databases. Most of the regulated genes associated with
      digestion, detoxification, homeostasis, and resistance were downregulated after
      ingestion of COTI. Meanwhile, several unigenes in the integrin signaling pathway
      might be involved in response to COTI. Furthermore, using comparative
      transcriptome analysis, we detected differently expressing genes and identified a
      new reference gene, UPF3, by qRT-polymerase chain reaction (PCR). Therefore, it
      was suggested that not only proteolysis inhibition, but also suppression of
      expression of genes involved in metabolism, development, signaling, and defense
      might account for the anti-insect resistance of COTI.

PMID- 29193259
TI  - Lipopolysaccharide levels adherent to PM2.5 play an important role in particulate
      matter induced-immunosuppressive effects in mouse splenocytes.
AB  - Epidemiological studies show that exposure to ambient particulate matter (PM) is
      associated with serious adverse health effects, including, but not limited to,
      those on the respiratory system. In the present study, we investigated the
      splenic response in mice administered PM of <= 2.5 MU m diameter (PM2.5). Male
      BALB/c mice (7 or 8 weeks old) were intratracheally administered PM2.5 (0.1 mg)
      four times, at 2 week intervals, and dissected 24 h after the final
      administration. The effect of six types of PM2.5, collected in Shenyang or
      Beijing (China) and Kitakyushu (Japan), on splenocytes was examined. Our results
      revealed a strong correlation between the levels of lipopolysaccharide (LPS), but
      not that of beta-glucan and polycyclic aromatic hydrocarbons, attached to PM2.5
      and the effect of PM2.5 on cell activity. PM2.5 with a low amount of LPS
      (PM2.5LL) reduced splenocyte mitogen-induced proliferation and cytokine
      production compared with that in control mice. The suppressive effects of PM2.5LL
      on proliferation and interleukin-2 production in splenocytes were rescued by the
      antioxidant N-acetylcysteine. Expression of heme oxygenase-1 was elevated after
      PM2.5LL administration, particularly in CD11b +  cells, while no elevation was
      observed in CD4+ , CD8+ or B220+ cells. Further, dissociation of the nuclear
      factor erythroid 2-related factor 2 from Kelch-like ECH-associating protein 1 was
      observed in splenocytes of PM2.5LL-administered mice. These data suggest that LPS
      attached to PM2.5 modulates the splenocyte immune responses to PM2.5.

PMID- 29193260
TI  - RACER-GRASP: Respiratory-weighted, aortic contrast enhancement-guided and coil
      unstreaking golden-angle radial sparse MRI.
AB  - PURPOSE: To develop and evaluate a novel dynamic contrast-enhanced imaging
      technique called RACER-GRASP (Respiratory-weighted, Aortic Contrast Enhancement
      guided and coil-unstReaking Golden-angle RAdial Sparse Parallel) MRI that extends
      GRASP to include automatic contrast bolus timing, respiratory motion
      compensation, and coil-weighted unstreaking for improved imaging performance in
      liver MRI. METHODS: In RACER-GRASP, aortic contrast enhancement (ACE) guided k
      space sorting and respiratory-weighted sparse reconstruction are performed using
      aortic contrast enhancement and respiratory motion signals extracted directly
      from the acquired data. Coil unstreaking aims to weight multicoil k-space
      according to streaking artifact level calculated for each individual coil during
      image reconstruction, so that coil elements containing a high level of streaking
      artifacts contribute less to the final results. Self-calibrating GRAPPA operator
      gridding was applied as a pre-reconstruction step to reduce computational burden
      in the subsequent iterative reconstruction. The RACER-GRASP technique was
      compared with standard GRASP reconstruction in a group of healthy volunteers and
      patients referred for clinical liver MR examination. RESULTS: Compared with
      standard GRASP, RACER-GRASP significantly improved overall image quality (average
      score: 3.25 versus 3.85) and hepatic vessel sharpness/clarity (average score:
      3.58 versus 4.0), and reduced residual streaking artifact level (average score:
      3.23 versus 3.94) in different contrast phases. RACER-GRASP also enabled
      automatic timing of the arterial phases. CONCLUSIONS: The aortic contrast
      enhancement-guided sorting, respiratory motion suppression and coil unstreaking
      introduced by RACER-GRASP improve upon the imaging performance of standard GRASP
      for free-breathing dynamic contrast-enhanced MRI of the liver. Magn Reson Med
      80:77-89, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 29193261
TI  - Metaanalysis of Mood and Substance Use Disorders in Proximal Risk for Suicide
      Deaths.
AB  - Evidence for proximal risk factors for suicide is based on case-control
      psychological autopsy studies, with these reports showing that mood and substance
      use disorders are the most prevalent mental disorders among suicide decedents
      worldwide and are associated with marked risk. However, moderators of risk and
      the degree of risk associated with (nonalcohol) drug use disorder are unknown. A
      comprehensive search was used to identify 35 case-control psychological autopsy
      studies published worldwide over a 30-year period that were metaanalyzed using
      random effects models. Major depression, odds ratio (95% confidence interval) =
      9.14 (5.53, 15.09), and drug use disorder, OR (95% CI) = 7.18 (3.22, 16.01), had
      large effect sizes, among other results. Risk estimates associated with major
      depression were greater in studies with a larger proportion of women and those
      conducted in Asia compared with other regions. There was no evidence of
      publication bias or that any one study had a disproportionate impact on findings.
      Risk for suicide associated with major depression appears to be moderated by sex
      and/or world region. Drug use disorder is a potent risk factor, illustrating the
      importance of assessing drug use in clinical risk assessment.

PMID- 29193262
TI  - Older individuals' need for knowledge and follow-up about their chronic atrial
      fibrillation, lifelong medical treatment and medical controls.
AB  - Older individuals with chronic atrial fibrillation (AF) often experience physical
      symptoms and feel psychologically unwell. In addition, these persons are
      prescribed lifelong medical treatment that requires regular monitoring. Through
      11 individual interviews, this interpretive description study aimed to explore
      and describe lifelong medical treatment and the need for medical controls as
      experienced from the perspective of older individuals living with chronic AF. The
      interviews were performed during 2014-2015; furthermore, they were recorded,
      transcribed verbatim and analysed for thematic patterns using thematic analysis
      inspired by Braun and Clarke. Ethical standards were followed throughout the
      study. The findings revealed one main theme: 'ambivalence in the need of
      knowledge' showing that lifelong medical treatment and the need for medical
      controls, in general, meant experiencing feelings of 'it doesn't matter, but it
      does matter' and 'being in the hands of the healthcare system'. The older persons
      lacked knowledge about their condition, which generated poor insight into their
      medical treatment and this in turn affected their daily life. They had thoughts
      and questions about their medication, but did not have an opportunity to ask the
      questions because of lack of follow-up from the healthcare system. The findings
      underscore the negative impact chronic AF has on older people's life and
      emphasises the need for follow-up and providing information from health care to
      these individuals.

PMID- 29193263
TI  - More scientific debate in caring sciences is needed.

PMID- 29193264
TI  - Role of Antheraea pernyi serpin 12 in prophenoloxidase activation and immune
      responses.
AB  - Serine protease inhibitors play a key role in the immune system of invertebrates
      by controlling proteolytic cascades. Besides its importance, the knowledge on
      immune functions of serpins in most of insects is fragmentary. In the present
      study, we identified serpin-12 from Antheraea pernyi encoding a predicted 402
      amino acid residue protein (Apserpin-12). We expressed the recombinant protein in
      Escherichia coli and the purified protein was used for the synthesis of rabbit
      anti-Apserpin-12 polyclonal antibodies and functional studies. Quantitative real
      time ploymerase chain reaction (qRT-PCR) analysis revealed that the knock-down of
      Apserpin-12 enhanced the prophenoloxidase (PPO) cascade stimulated by Micrococcus
      luteus in hemolymph, whereas addition of recombinant Apserpin-12 protein along
      with same elicitor led to down-regulate PPO activation. Following different
      microbial challenge (E. coli, Beauveria bassiana, M. Luteus, and nuclear
      polyhedrosis virus), the expression of Apserpin-12 mRNA was induced
      significantly. Furthermore, the Apserpin-12 double-stranded RNA administration
      elicited the expression of antimicrobial peptides, while the treatment with
      recombinant protein suppressed their expression. Tissue profile of Apserpin-12
      indicated that it is expressed in all examined tissues, that is, hemolymph,
      malpighian tubules, midgut, silk gland, integument, and fat body with variation
      in their transcript levels. We concluded that Apserpin-12 may regulate PPO
      activation and inhibit the production of antimicrobial peptides in A. pernyi,
      suggesting important role in its immune system.

PMID- 29193265
TI  - Substance use disorder and compulsory commitment to care: a care-ethical decision
      making framework.
AB  - In the era of deinstitutionalisation of psychiatric patients, steady or even
      increasing rates of compulsory commitment to care (CCC) are an intriguing
      phenomenon to analyse. From a clinical, legal and ethical perspective, CCC
      continues to be a controversial practice in psychiatry, and perhaps even more so
      when applied to patients with severe substance use disorder (SUD). Several
      reasons make it controversial. The lack of consensus about the benefits of CCC
      and professional disagreement about what mental illness and autonomy mean in the
      case of SUD make it difficult to apply ethically sound clinical decision-making
      in CCC. Also, the medico-legal framework underlying CCC use sometimes appears to
      foster the use of reductionist clinical evaluation. Layered on top of these
      issues is how stakeholders view coercion. There is a discrepancy between
      clinicians' and patients' perception of coercion, which leads to clinician
      patient differences on whether CCC is necessary. Moreover, the way in which the
      evaluation is typically carried out influences patients' perception of coercion
      and subsequently their motivation for participating fully in treatment. In this
      article, we explore the value of care ethics, often applied to care practices
      such as nursing, when applied to more procedural medical practices, such as
      decision-making regarding CCC. The care-ethical approach views decision-making as
      part of a dynamic care process, within which the lived experience, interpretative
      dialogue and promotion of dignity are core features. Embracing this new framework
      means a paradigm shift in when the therapeutic relationship begins, namely,
      investing in it occurs while conducting an evaluation for a possible CCC
      procedure. Unlike in current typical evaluations, early cultivation of the
      therapeutic relationship enables the patient to participate in the definition of
      his needs, reduces perceived coercion and negative emotions and enhances
      treatment motivation. Finally, implications of this novel approach for clinical
      practice are formulated and discussed.

PMID- 29193266
TI  - Motion-tolerant diffusion mapping based on single-shot overlapping-echo
      detachment (OLED) planar imaging.
AB  - PURPOSE: A new diffusion-mapping method based on single-shot overlapping-echo
      detachment (DM-OLED) planar-imaging sequence, along with a corresponding
      separation algorithm, is proposed to achieve reliable quantitative diffusion
      mapping in a single shot. The method can resist the effects of motion and help in
      detecting the quick variation of diffusion under different physiological status.
      METHODS: The echo-planar imaging method is combined with two excitation pulses
      with small flip angle to gain overlapping-echo signal in a single shot. Then the
      overlapping signals are separated by a separation algorithm and used for
      diffusion computation. Numerical simulation, phantom, and in vivo rat experiments
      were performed to verify the efficiency, accuracy, and motion tolerance of DM
      OLED. RESULTS: The DM-OLED sequence could obtain reliable diffusion maps within
      milliseconds in numerical simulation, phantom, and in vivo experiments. Compared
      with conventional diffusion mapping with spin-echo echo-planar imaging, DM-OLED
      has higher time resolution and fewer motion-incurred errors in the apparent
      diffusion coefficient maps. CONCLUSIONS: As a reliable fast diffusion measurement
      tool, DM-OLED shows promise for real-time dynamic diffusion mapping and
      functional magnetic resonance imaging. Magn Reson Med 80:200-210, 2018. (c) 2017
      International Society for Magnetic Resonance in Medicine.

PMID- 29193267
TI  - Lifelong Maintenance of Oral Tolerance and Immunity Profiles in Mice Depends on
      Early Exposure to Antigen.
AB  - Oral tolerance is defined as a state of systemic hyporesponsiveness to an antigen
      that has been previously administered by the oral route. Many factors affect oral
      tolerance induction; some of them related to antigen, and some related to the
      animal. The age of the animal is one of the most important factors that affect
      oral tolerance as ageing brings many alterations in immune responses. Herein, we
      demonstrated that both the oral tolerance and pattern of immune reactivity
      triggered in early life were kept up to 15 months regarding the magnitude of
      antibody production, cell proliferation and cytokine profile when compared to
      immune responses induced in old mice. Therefore, our results corroborate with a
      promising proposal for prevaccination during childhood and young age, and a
      booster in older age, to make sure that the primary immunization in early life is
      not lost in aged individuals.

PMID- 29193268
TI  - What role does heritability play in transgenerational phenotypic responses to
      captivity? Implications for managing captive populations.
AB  - Animals maintained in captivity exhibit rapid changes in phenotypic traits, which
      may be maladaptive for natural environments. The phenotype can shift away from
      the wild phenotype via transgenerational effects, with the environment
      experienced by parents influencing the phenotype and fitness of offspring. There
      is emerging evidence that controlling transgenerational effects could help
      mitigate the effects of captivity, improving the success of captively bred
      animals post release. However, controlling transgenerational effects requires
      knowledge of the mechanisms driving transgenerational changes. To better
      understand the genetic mechanisms that contribute to transgenerational effects in
      captivity we investigated the heritability of behavioral phenotypes using mid
      parent- and single parent-offspring regressions in a population of captive-reared
      house mouse (Mus musculus) that we had previously shown exhibit transgenerational
      changes in boldness and activity behavioral types. Slopes for boldness and
      activity were all positive, indicating a low to moderate degree of heritability.
      Though, none of the heritability estimates were statistically significant due to
      the large surrounding errors. However, the large error surrounding the
      heritability estimates may also indicate that there is variability in
      heritability between behavioral traits within the boldness and activity
      behavioral types. The implication of this finding is that the potential for
      heritable genetic changes in captivity varies considerably between traits. We
      conclude that continued investigation of the potential for traits to evolve in
      captivity is needed to better inform captive breeding and reintroduction
      programs.

PMID- 29193269
TI  - Additive effects of PNPLA3 and TM6SF2 on the histological severity of non
      alcoholic fatty liver disease.
AB  - BACKGROUND AND AIM: We investigated the effects of PNPLA3 rs738409, TM6SF2
      rs58542926, and MBOAT7-TMC4 rs641738 variants on metabolic phenotypes and their
      combined effects on the histological severity of non-alcoholic fatty liver
      disease (NAFLD). METHODS: We genotyped rs738409, rs58542926, and rs641738 in
      biopsy-proven NAFLD patients (n = 416) and healthy controls (n = 109).
      Homeostasis model assessment of insulin resistance and adipose tissue insulin
      resistance were calculated. RESULTS: The rs738409 and rs58542926 variants, but
      not rs641738, were associated not only with non-alcoholic steatohepatitis (NASH)
      (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46-2.73 and OR, 1.91; 95%
      CI, 1.04-3.51) but also with significant fibrosis (>= F2) (OR, 1.53; 95% CI, 1.11
      2.11 and OR, 1.88; 95% CI, 1.02-3.46) in NAFLD, even after adjustment for
      metabolic risk factors. Of both variants, only rs738409 was associated with
      homeostasis model assessment of insulin resistance and adipose tissue insulin
      resistance even in healthy controls (P = 0.046 and 0.002, respectively) as well
      as in the entire study cohort (P = 0.016 and 0.048, respectively). PNPLA3 and
      TM6SF2 risk variants additively increased the risk of NASH and significant
      fibrosis (OR per risk allele, 2.03; 95% CI, 1.50-2.73 and 1.61; 95% CI, 1.19
      2.17). Even in subjects with low insulin resistance, the risk of NASH or
      significant fibrosis increased as the number of risk alleles increased (P = 0.008
      and 0.020, respectively). CONCLUSIONS: PNPLA3 and TM6SF2 determine the risk of
      NASH and significant fibrosis, even after adjustment for insulin resistance, and
      exert an additive effect on NASH and significant fibrosis.

PMID- 29193270
TI  - Comments on "Ileocecal vascularized lymph node transfer for the treatment of
      extremity lymphedema: A case report".

PMID- 29193271
TI  - Extracorporeal photopheresis for graft versus host disease: Identifying a
      clinical pathway and associated resource utilization.
AB  - Extracorporeal photopheresis (ECP) is an established therapy for the treatment of
      graft-versus-host-disease (GVHD) following an allogeneic stem cell transplant. We
      performed a prospective analysis of patients receiving ECP treatment for GVHD to
      identify a clinical pathway and resource utilization of this process. The cohort
      included consecutive allogeneic stem cell recipients with GVHD. ECP was performed
      using the CELLEX Photopheresis System or the UVAR XTS Photopheresis System
      (Therakos, Inc, Exton, PA). A clinical pathway was developed and a time and
      motion study was conducted to define the resource utilization and costs
      associated with ECP. Patients were treated with either CELLEX (n = 18 procedures)
      or UVAR (n = 4 procedures). Total time commitment for each procedure for the 2
      machines differed. The time for ECP was 117 min (median, range: 91-164 min) using
      CELLEX and 161 min (median; range: 140-210) using the UVAR-XTS machine. Total
      costs of each ECP procedure were $3420.50. There is a considerable time
      commitment of the patient and the clinical staff when employing ECP to treat
      GVHD. ECP costs are significant considering this is a prolonged therapy continued
      for several months. With this finalized pathway and costs, we have a standardized
      clinical pathway for the treatment of GVHD. We are addressing minimizing resource
      utilization while emphasizing quality care for these patients.

PMID- 29193272
TI  - Synergism of amlodipine and candesartan on blood pressure reduction and organ
      protection in hypertensive rats.
AB  - This study was designed to investigate the possible synergism of amlodipine and
      candesartan on the reduction of blood pressure (BP) in hypertensive rats. The end
      organ protection was also observed. In acute experiment, spontaneously
      hypertensive rats (SHRs) were treated with intragastric administration of
      amlodipine (0.5, 1, 2, 3 mg/kg), candesartan (1, 2, 3, 4, 6, 8 mg/kg), and 14
      different combinations to find the possible ratio of synergistic interaction. In
      two kidneys, one clip (2K1C) rats, the effects of amlodipine (1 mg/kg),
      canderastan (2 mg/kg) and their combination on BP reduction were also observed.
      In chronic study, SHRs were treated with amlodipine (1 mg/kg), candesartan (2
      mg/kg), and their combination for 5 months. Organ damage evaluation was performed
      after BP recording. The probability sum test (q test) was used to evaluate the
      synergistic action. There is a synergistic interaction between amlodipine and
      candesartan on BP reduction. The optimal dose ratio is 1:2. The synergistic
      effect was also confirmed by 2K1C hypertensive rats. In chronic study, this
      combination (1:2) possessed an obvious synergism on the reduction of BP and BP
      variability (BPV) and protection on end organs. Multiple regression analysis
      showed that heart and aortic hypertrophy indexes and glomerular damage parameters
      were positively related to BP and BPV. In conclusion, combination of amlodipine
      and candesartan exhibited a potent antihypertensive effect and possessed an
      obvious synergism on BP reduction and organ protection in hypertension. The
      optimal proportion was 1:2. BP and BPV reduction may both importantly contribute
      to end organ protection.

PMID- 29193273
TI  - Activation of caspase-6 and cleavage of caspase-6 substrates is an early event in
      NMDA receptor-mediated excitotoxicity.
AB  - Excitotoxicity, due to overstimulation of N-methyl D-aspartate receptors
      (NMDARs), has a pivotal role in many neurological disorders. However, NMDAR
      antagonists often cause side effects, and identifying more druggable therapeutic
      targets for NMDAR excitotoxicity is an important goal. Activation of caspases is
      a downstream effect of excitotoxicity that may be critically involved in NMDAR
      mediated cell death. Caspase-6 (casp6) in particular has been shown to play a key
      role in the pathogenesis of stroke, Huntington disease, and Alzheimer disease.
      Using N-methyl D-aspartate (NMDA)-induced excitotoxic injuries of primary rat
      neurons, we demonstrate that there is an early increase in caspase profiles after
      an excitotoxic event at the level of mRNA, protein, and activity. Casp6 is
      elevated and activated first, followed by caspase-8 and caspase-3. Similarly,
      known casp6 substrates huntingtin, as well as novel casp6 substrates
      serine/threonine kinase 3 and death domain-associated protein, are cleaved in
      similar temporal patterns post NMDA. On the basis of these data, we propose that
      casp6 may be an initiator caspase in apoptotic cascades leading to neuronal death
      after an excitotoxic event and suggest casp6 as a potential therapeutic target
      for neurological disorders where NMDAR-mediated excitotoxicity has been shown to
      play a role.

PMID- 29193275
TI  - Homozygous frame-shift mutation in a Chinese family with neurofibromatosis type
      1.

PMID- 29193274
TI  - Melatonin therapy reduces the risk of osteoporosis and normalizes bone formation
      in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a common autoimmune and neurodegenerative disease of
      the central nervous system. Serum levels of melatonin decrease in MS patients who
      are also at risk of osteoporosis. Procalcitonin (proCT) has been reported as a
      biomarker of systemic inflammation and autoimmune disease; however, its changes
      in MS patients have not been well explored. This study investigated, using ELISA,
      the clinical correlation between serum melatonin and proCT in MS patients. We
      then assessed the effect of melatonin (10 mg/kg) therapy on bone metabolism and
      osteoporosis in experimental autoimmune encephalomyelitis (EAE) model of MS and
      in MS patients. Data showed a significant increase (*P < 0.05) in serum levels of
      proCT in MS patients, inversely correlated (r  =  -0.945; P  =  0.0001) with
      melatonin levels, compared to healthy participants. On the other hand, melatonin
      therapy ameliorated EAE severity by significantly decreasing (*P < 0.05) mean
      clinical scores, compared to control EAE mice. In addition, serum levels of proCT
      significantly (**P < 0.01) increased in EAE mice, compared to controls, which was
      significantly (*P < 0.05) reduced by melatonin. Moreover, EAE-induced decrease in
      25-hydroxyvitamin D, calcium, and osteocalcin (OCN) in EAE mice, compared to
      controls, was significantly (*P < 0.05) increased by melatonin. Finally, OCN
      serum levels were found to be significantly decreased (*P < 0.05) in MS patients,
      in comparison with controls. Taken together, we suggest that proCT could be used
      as a diagnostic biomarker in MS patients and that melatonin normalizes bone
      metabolites in MS. Further clinical and experimental investigations are needed to
      understand bone metabolism in MS.

PMID- 29193276
TI  - Review shows that using surfactant a number of times or as a vehicle for
      budesonide may reduce the risk of bronchopulmonary dysplasia.
AB  - AIM: Bronchopulmonary dysplasia (BPD) remains the most common respiratory
      morbidity in immature infants. This review describes the diagnosis of BPD has
      evolved and summarises the therapeutic approaches that have made it possible to
      limit the incidence of BPD. METHOD: We reviewed the literature from the first
      definition of BPD by Northway in 1967 to the surfactant treatment policies that
      are currently in use, drawing on more than 50 papers up to 2017. RESULTS: Our
      review showed that improvements in neonatal survival have been associated with an
      increased risk of severe BPD, significant levels of long-term morbidity and the
      increased use of healthcare resources. These issues have encouraged researchers
      to explore potential new treatments that limit the incidence of BPD. Repeated
      surfactant instillation and the use of surfactant as a vehicle for budesonide are
      promising strategies for alleviating the burden of chronic lung disease. Ongoing
      research on surfactant or stem cell therapy may further improve the respiratory
      prognosis for prematurely born children. CONCLUSION: Considerable research has
      been carried out into the increase in BPD, which has resulted from improvements
      in neonatal survival. Key areas of research include repeated surfactant
      administration, using surfactant as a vehicle for budesonide and stem cell
      therapy.

PMID- 29193278
TI  - DNP-enhanced solid-state NMR spectroscopy of active pharmaceutical ingredients.
AB  - Solid-state NMR spectroscopy has become a valuable tool for the characterization
      of both pure and formulated active pharmaceutical ingredients (APIs). However,
      NMR generally suffers from poor sensitivity that often restricts NMR experiments
      to nuclei with favorable properties, concentrated samples, and acquisition of one
      dimensional (1D) NMR spectra. Here, we review how dynamic nuclear polarization
      (DNP) can be applied to routinely enhance the sensitivity of solid-state NMR
      experiments by one to two orders of magnitude for both pure and formulated APIs.
      Sample preparation protocols for relayed DNP experiments and experiments on
      directly doped APIs are detailed. Numerical spin diffusion models illustrate the
      dependence of relayed DNP enhancements on the relaxation properties and particle
      size of the solids and can be used for particle size determination when the other
      factors are known. We then describe the advanced solid-state NMR experiments that
      have been enabled by DNP and how they provide unique insight into the molecular
      and macroscopic structure of APIs. For example, with large sensitivity gains
      provided by DNP, natural isotopic abundance, 13 C-13 C double-quantum single
      quantum homonuclear correlation NMR spectra of pure APIs can be routinely
      acquired. DNP also enables solid-state NMR experiments with unreceptive
      quadrupolar nuclei such as 2 H, 14 N, and 35 Cl that are commonly found in APIs.
      Applications of DNP-enhanced solid-state NMR spectroscopy for the molecular level
      characterization of low API load formulations such as commercial tablets and
      amorphous solid dispersions are described. Future perspectives for DNP-enhanced
      solid-state NMR experiments on APIs are briefly discussed.

PMID- 29193277
TI  - Spectrophotometry and Ultracentrifugation for Measurement of Plasma Lipids in
      Dogs with Diabetes Mellitus.
AB  - BACKGROUND: There are conflicting reports of plasma lipoprotein lipid content in
      dogs with diabetes mellitus (DM). OBJECTIVES: To determine lipoprotein lipid
      content of plasma of dogs with DM by spectrophotometry and ultracentrifugation;
      to compare lipoprotein lipid content in diabetic and healthy dogs; and to
      quantify apolipoprotein B-100 (ApoB) in dogs with DM. ANIMALS: 22 dogs with DM
      and 9 healthy dogs. METHODS: Cross-sectional study. Triglyceride (TG), total
      cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) concentrations
      were measured by spectrophotometry. Very low-density lipoprotein cholesterol
      (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were
      calculated after ultracentrifugation. Non-HDL-C cholesterol was calculated by
      subtracting HDL-C from TC. ApoB was quantified by ELISA. The Mann-Whitney test
      was used for comparison of median lipoprotein concentrations, and Spearman's
      correlation was used to assess associations between ApoB and lipoprotein
      fractions. RESULTS: All values are reported in mg/dL. Median TG (122), TC
      (343.5), HDL-C, (200), VLDL-C, (27) LDL-C (68), non-HDL-C (114), and ApoB (320)
      were significantly higher in dogs with DM, compared to healthy dogs (57, 197,
      168, 12, 16, 31, and 258, respectively, P-values 0.0079, <0.001, 0.029, 0.011,
      <0.001, <0.001, 0.025, respectively). A significant association was found between
      ApoB and LDL-C (Spearman's rho = 0.41, P = 0.022) and between ApoB and non-HDL-C
      (Spearman's rho = 0.40, P = 0.027). CONCLUSIONS AND CLINICAL IMPORTANCE:
      Dyslipidemia of dogs with DM is characterized by pronounced increases in LDL-C
      and non-HDL-C concentrations, although all lipoprotein fractions are
      significantly increased. Knowledge of specific lipoprotein fraction alterations
      in dogs with DM can enhance treatment options for diabetic dyslipidemia in dogs.

PMID- 29193279
TI  - Numerical and Experimental Evaluation of High-Intensity Focused Ultrasound
      Induced Lesions in Liver Tissue Ex Vivo.
AB  - OBJECTIVES: Recent advances in the field of acoustics and piezoelectric and
      ultrasound transducers have led to new approaches to the diagnosis and treatment
      of certain diseases. One method of treatment with ultrasonic waves is high
      intensity focused ultrasound (HIFU) treatment, which is a thermal therapeutic
      method used to treat malignant tumors. Although a variety of treatment-planning
      strategies using ultrasonic waves have been investigated, little clinical success
      has been achieved. Computational modeling is a powerful tool for predicting
      device performance. METHODS: The heating induced by a concave transducer with
      operating powers of 85 and 135 W was studied, and the experimental results
      presented in this article verify its applicability. Numerical simulations of the
      nonlinear acoustic field were performed by using the Westervelt and Khokhlov
      Zabolotskaya-Kuznetsov equations. Heat transfer was measured for the 2
      operational powers, and the results were compared with ex vivo experimental
      results. In addition, thermal dose contours for both the simulation and
      experimental results were calculated to investigate the ablated area. RESULTS:
      Good agreement was found between the experimental and numerical results. The
      results show that the average temperature deviations calculated at the focal
      point were 12.8% and 4.3% for transducer powers of 85 and 135 W, respectively.
      CONCLUSIONS: This study provides guidance to HIFU practitioners in determining
      lesion size and identifying nonlinear effects that should be considered in HIFU
      procedures.

PMID- 29193280
TI  - Novel endoscopic categorization for prediction of chemoradiotherapy response in
      locally advanced esophageal cancer.
AB  - BACKGROUND AND AIM: Preoperative chemoradiotherapy (CRT) followed by
      esophagectomy is a well-known treatment modality for patients with locally
      advanced esophageal cancer (EC). This study developed an algorithm to predict
      pathological complete response (CR) in these patients using post-CRT endoscopic
      category with biopsy and validated the proposed algorithm. METHODS: A
      retrospective review of 141 consecutive patients who completed preoperative CRT
      and underwent surgical resection for locally advanced EC was performed. The post
      CRT endoscopic findings of each patient were stratified into five categories.
      RESULTS: The distribution of post-CRT endoscopic categories was significantly
      different between the pathological CR and non-pathological CR groups (P < 0.001).
      About 76.8% (73/95) of patients in category 0, 1, or 2 achieved pathological CR.
      In contrast, 91.3% (42/46) of endoscopic categories 3 and 4 patients did not
      achieve pathological CR. Sensitivity of post-CRT biopsy was 11.1%. Therefore, an
      algorithm combining biopsy results and dichotomized post-CRT endoscopic category
      (category 0, 1, or 2 vs category 3 or 4) was developed. The sensitivity,
      specificity, and accuracy in predicting pathological CR by the proposed algorithm
      were 64.8%, 95.9%, and 82.8%, respectively. In the multivariate analysis, the
      proposed algorithm remained a significant negative factor of survival (P <
      0.001). CONCLUSIONS: Algorithm using post-CRT endoscopic category with biopsy may
      help identify locally advanced EC patients who achieved pathological CR after
      preoperative CRT. Modalities to accurately detect subepithelial remnant EC may
      further aid in predicting pathological CR.

PMID- 29193281
TI  - A randomised trial of enteral glutamine supplementation for very preterm children
      showed no beneficial or adverse long-term neurodevelopmental outcomes.
AB  - AIM: This study evaluated the long-term effects of enteral glutamine
      supplementation on neurodevelopmental outcomes of a Dutch cohort of very preterm
      children at 13 years of age. METHODS: The cohort was enrolled in a randomised
      placebo-controlled trial between 2001 and 2003 in which infants received
      glutamine- or alanine-supplemented enteral nutrition during the first month of
      life. Participants were invited for follow-up at a mean age of 13.30 years.
      Motor, neurocognitive, academic and behavioural outcomes were assessed in 61
      children. RESULTS: No differences were found between the groups regarding motor,
      intellectual, academic and behavioural functioning. Forward span visuospatial
      working memory performance was better in the controls (crude/adjusted model: d =
      0.67/0.64, p = 0.02/0.02), but no difference was found for backward span. After
      the data were adjusted for confounders, the groups differed regarding parent
      rated attention (crude/adjusted model: d = 0.47/0.73, p = 0.07/0.003), but both
      groups scored within the normal range. CONCLUSION: This was the first study on
      the long-term effects of enteral glutamine supplementation on the
      neurodevelopmental outcomes of very preterm children. Our study provided no
      evidence that enteral glutamine supplementation had any beneficial or adverse
      effects on the children's motor, neurocognitive, academic and behavioural
      outcomes at 13 years of age.

PMID- 29193282
TI  - A hot-water extract of Sanguisorba officinalis ameliorates endotoxin-induced
      septic shock by inhibiting inflammasome activation.
AB  - The inflammasome is a multiprotein signaling complex that mediates inflammatory
      innate immune responses through caspase 1 activation and subsequent IL-1beta
      secretion. However, because its aberrant activation often leads to inflammatory
      diseases, targeting the inflammasome holds promise for the treatment of
      inflammation-related diseases. In this study, it was found that a hot-water
      extract of Sanguisorba officinalis (HSO) suppresses inflammasome activation
      triggered by adenosine 5'-triphosphate, nigericin, microbial pathogens, and
      double stranded DNA in bone marrow-derived macrophages. HSO was found to
      significantly suppress IL-1beta production in a dose-dependent manner; this
      effect correlated well with small amounts of caspase 1 and little ASC pyroptosome
      formation in HSO-treated cells. The anti-inflammatory activity of HSO was further
      confirmed in a mouse model of endotoxin-induced septic shock. Oral administration
      of HSO reduced IL-1beta titers in the serum and peritoneal cavity, increasing the
      survival rate. Taken together, our results suggest that HSO is an inhibits
      inflammasome activation through nucleotide-binding domain and leucine-rich repeat
      pyrin domain 3, nucleotide-binding domain and leucine-rich repeat caspase
      recruitment domain 4 and absent in melanoma 2 pathways, and may be useful for
      treatment of inflammasome-mediated diseases.

PMID- 29193283
TI  - Diastolic dysfunction in pulmonary artery hypertension: Creatine kinase and the
      potential therapeutic benefit of beta-blockers.
AB  - Passive properties of the myocardium influence diastolic filling and cardiac
      output. In heart failure, changes in contributors to the passive properties of
      the ventricle, such as titin and collagen, and loss of the metabolic enzyme
      creatine kinase, increase resistance to filling resulting in diastolic
      dysfunction. Pulmonary artery hypertension (PAH) arises from interactions between
      the pulmonary vasculature and the right ventricle (RV) which ultimately leads to
      RV failure. Beta1-adrenergic receptor blockers (BB) act on the myocardium and are
      beneficial in left heart failure but are not used in PAH. We investigated whether
      BB improved survival and RV function in a rat model of PAH. Rats were injected
      with monocrotaline (60 mg/kg) to induce PAH and RV failure, or saline as controls
      (CON). When PAH was established, rats were treated with metoprolol (10 mg/kg per
      day) (MCT+BB) or vehicle (sucrose) (MCT); CON were treated with vehicle. In vivo
      measurement of RV compliance using pressure-volume catheter, indicated diastolic
      dysfunction in the RV of MCT rats was improved with BB treatment. Expression of
      creatine kinase protein and mRNA was lower in MCT rats compared to CON, with a
      trend for reversion by BB treatment. Isolated CON RV myocytes had a positive
      contraction response to faster pacing, whereas it was negative in MCT. MCT+BB
      cells had an intermediate response, indicating improved ability to respond to
      increased demand. BB improved diastolic function, partially restored metabolic
      enzymes and augmented contractility in PAH. These data support the hypothesis
      that BB may be beneficial in PAH by supporting RV function.

PMID- 29193285
TI  - Bioaccumulation, uptake, and toxicity of carbamazepine in soil-plant systems.
AB  - Since the detection of active pharmaceutical ingredients (APIs) in various
      environmental media, research has explored the potential uptake and toxicity of
      these chemicals to species inhabiting these matrices. Specifically,
      pharmaceuticals, including the antiepileptic API carbamazepine (CBZ), are taken
      up from soil by a range of plants. Many short-term studies have also suggested
      that certain APIs induce toxicity in plants. However, the effects of APIs on
      fruiting plants remain relatively unexplored. The present study investigated the
      uptake, bioaccumulation, and toxicity of CBZ in Cucurbita pepo (zucchini) from
      seed to full maturity across a range of CBZ exposure concentrations in soil (0.1
      20 mg/kg). Results of biomass, chlorophyll, starch and total nitrogen (N)
      concentration in C. pepo indicated toxicity at soil concentrations of >=10 mg/kg.
      There were clear visual indications of increasing toxicity on leaves, including
      chlorosis and necrosis, from soil concentrations of 1 up to 20 mg/kg. The present
      study also revealed novel insights into the effect of CBZ accumulation on C. pepo
      fruiting: female C. pepo flowers were unable to set fruit when leaf
      concentrations were >=14 mg/kg. These findings may have implications for future
      agricultural productivity in areas where reclaimed wastewater containing APIs is
      a source of irrigation. Detectable CBZ concentrations were found in edible C.
      pepo fruit, indicating the possibility of trophic transfer. Environ Toxicol Chem
      2018;37:1122-1130. (c) 2017 SETAC.

PMID- 29193284
TI  - Drug burden index to define the burden of medicines in older adults with
      intellectual disabilities: An observational cross-sectional study.
AB  - AIMS: The drug burden index (DBI) is a dose-related measure of anticholinergic
      and sedative drug exposure. This cross-sectional study described DBI in older
      adults with intellectual disabilities (ID) and the most frequently reported
      therapeutic classes contributing to DBI and examined associations between higher
      DBI scores and potential adverse effects as well as physical function. METHODS:
      This study analysed data from Wave 2 (2013/2014) of the Intellectual Disability
      Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a
      representative study on the ageing of people with ID in Ireland. Self- and
      objectively-reported data were collected on medication use and physical health,
      including health conditions. The Barthel index was the physical function measure.
      RESULTS: The study examined 677 individuals with ID, of whom 644 (95.1%) reported
      taking medication and 78.6% (n = 532) were exposed to medication with
      anticholinergic and/or sedative activity. 54.2% (n = 367) were exposed to high
      DBI score (>=1). Adjusted multivariate regression analysis revealed no
      significant association between DBI score and daytime dozing, constipation or
      falls. After adjusting for confounders (sex, age, level of ID, comorbidities,
      behaviours that challenge, history of falls), DBI was associated with
      significantly higher dependence in the Barthel index (P = 0.002). CONCLUSIONS:
      This is the first time DBI has been described in older adults with ID. Scores
      were much higher than those observed in the general population and higher scores
      were associated with higher dependence in Barthel index activities of daily
      living.

PMID- 29193286
TI  - Understanding ED performance after the implementation of activity-based funding.
AB  - OBJECTIVE: The aim of this study was to describe emergency department (ED)
      activities and staffing after the introduction of activity-based funding (ABF) to
      highlight the challenges of new funding arrangements and their implementation.
      METHODS: A retrospective study of public hospital EDs in Queensland, Australia,
      was undertaken for 2013-2014. The ED and hospital characteristics are described
      to evaluate the alignment between activity and resourcing levels and their impact
      on performance. RESULTS: Twenty EDs participated (74% response rate). Weighted
      activity units (WAUs) and nursing staff varied based on hospital type and size.
      Larger hospital EDs had on average 9076 WAUs and 13 full time equivalent (FTE)
      nursing staff per 1000 WAUs; smaller EDs had on average 4587 WAUs and 10.3 FTE
      nursing staff per 1000 WAUs. Medical staff was relatively consistent (8.1-8.7 FTE
      per 1000 WAUs). The proportion of patients admitted, discharged, or transferred
      within 4 hours ranged from 73% to 79%. The ED medical and nursing staffing
      numbers did not correlate with the 4-hour performance. CONCLUSION: Substantial
      variation exists across Queensland EDs when resourcing service delivery in an
      activity-based funding environment. Historical inequity persists in the staffing
      profiles for regional and outer metropolitan departments. The lack of association
      between resourcing and performance metrics provides opportunity for further
      investigation of efficient models of care.

PMID- 29193287
TI  - Sensitivity enhancement for detection of hyperpolarized 13 C MRI probes with 1 H
      spin coupling introduced by enzymatic transformation in vivo.
AB  - PURPOSE: Although 1 H spin coupling is generally avoided in probes for
      hyperpolarized (HP) 13 C MRI, enzymatic transformations of biological interest
      can introduce large 13 C-1 H couplings in vivo. The purpose of this study was to
      develop and investigate the application of 1 H decoupling for enhancing the
      sensitivity for detection of affected HP 13 C metabolic products. METHODS: A
      standalone 1 H decoupler system and custom concentric 13 C/1 H paddle coil setup
      were integrated with a clinical 3T MRI scanner for in vivo 13 C MR studies using
      HP [2-13 C]dihydroxyacetone, a novel sensor of hepatic energy status. Major 13 C
      1 H coupling JCH  = ~150 Hz) is introduced after adenosine triphosphate-dependent
      enzymatic transformation of HP [2-13 C]dihydroxyacetone to [2-13 C]glycerol-3
      phosphate in vivo. Application of WALTZ-16 1 H decoupling for elimination of
      large 13 C-1 H couplings was first tested in thermally polarized glycerol
      phantoms and then for in vivo HP MR studies in three rats, scanned both with and
      without decoupling. RESULTS: As configured, 1 H-decoupled 13 C MR of thermally
      polarized glycerol and the HP metabolic product [2-13 C]glycerol-3-phosphate was
      achieved at forward power of approximately 15 W. High-quality 3-s dynamic in vivo
      HP 13 C MR scans were acquired with decoupling duty cycle of 5%. Application of 1
      H decoupling resulted in sensitivity enhancement of 1.7-fold for detection of
      metabolic conversion of [2-13 C]dihydroxyacetone to HP [2-13 C]glycerol-3
      phosphate in vivo. CONCLUSIONS: Application of 1 H decoupling provides
      significant sensitivity enhancement for detection of HP 13 C metabolic products
      with large 1 H spin couplings, and is therefore expected to be useful for
      preclinical and potentially clinical HP 13 C MR studies. Magn Reson Med 80:36-41,
      2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 29193289
TI  - Disproportionate Mental Health Burden Associated With Past-Year Intimate Partner
      Violence Among Women Receiving Care in the Veterans Health Administration.
AB  - Experience of intimate partner violence (IPV) can lead to mental health
      conditions, including anxiety, depression, and unhealthy substance use. Women
      seen in the Veterans Health Administration (VHA) face high rates of both IPV and
      mental health morbidity. This study aimed to identify associations between recent
      IPV experience and mental health diagnoses among women VHA patients. We examined
      medical records data for 8,888 female veteran and nonveteran VHA patients across
      13 VHA facilities who were screened for past-year IPV between April, 2014 and
      April, 2016. Compared with women who screened negative for past-year IPV (IPV-),
      those who screened positive (IPV+; 8.7%) were more than twice as likely to have a
      mental health diagnosis, adjusted odds ratio (AOR) = 2.27, 95% confidence
      interval (CI) [1.95, 2.64]; or more than two mental health diagnoses, AOR = 2.29,
      95% CI [1.93, 2.72]). Screening IPV+ was also associated with significantly
      higher odds of each type of mental health morbidity (AOR range = 1.85-3.19)
      except psychoses. Over half (53.5%) of the women who screened IPV+ had a mental
      health diagnosis, compared with fewer than one-third (32.6%) of those who
      screened IPV-. Each subtype of IPV (psychological, physical, and sexual violence)
      was significantly associated with having a mental health diagnosis (AOR range =
      2.25-2.37) or comorbidity (AOR range = 2.17-2.78). Associations remained when
      adjusting for military sexual trauma and combat trauma among the veteran
      subsample. These findings highlight the mental health burden associated with past
      year IPV among female VHA patients and underscore the need to address
      psychological and sexual IPV, in addition to physical violence.

PMID- 29193288
TI  - Characterization of tumor vascular permeability using natural dextrans and CEST
      MRI.
AB  - PURPOSE: To investigate the use of natural dextrans as nano-sized chemical
      exchange saturation transfer (CEST) MRI probes for characterizing size-dependent
      tumor vascular permeability. METHODS: Dextrans of different molecular weight (10,
      70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N = 5)
      bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD
      (D10, 6 nm) and 70 kD (D70, 12 nm) dextran at a dose of 375 mg/kg. The CEST-MRI
      signal in the tumors was assessed before and approximately 40 min after each
      injection using a dynamic CEST imaging scheme. RESULTS: All dextrans of different
      molecular weights have a strong CEST signal with an apparent maximum of
      approximately 0.9 ppm. The detectability and effects of pH and saturation
      conditions (B1 and Tsat ) were investigated. When applied to CT26 tumors, the
      injection of D10 could produce a significant "dexCEST" enhancement in the
      majority of the tumor area, whereas the injection of D70 only resulted in an
      increase in the tumor periphery. Quantitative analysis revealed the differential
      permeability of CT26 tumors to different size particles, which was validated by
      fluorescence imaging and immunohistochemistry. CONCLUSIONS: As a first
      application, we used 10- and 70-kD dextrans to visualize the spatially variable,
      size-dependent permeability in the tumor, indicating that nano-sized dextrans can
      be used for characterizing tumor vascular permeability with dexCEST MRI and,
      potentially, for developing dextran-based theranostic drug delivery systems. Magn
      Reson Med 79:1001-1009, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 29193290
TI  - The 1st step initiation essential for allergen-specific IgE antibody production
      upon the 2nd step: Induction of non-specific IgE+ small B cells containing
      secondly-sensitized allergen-specific ones in mice firstly-sensitized with an
      allergen.
AB  - There was a significant amount of non-specific, but not of allergen (e.g.,
      papain, mite feces and four kinds of pollen)-specific, IgE antibodies (Abs) in
      the sera of normal mice. An i.n. injection of each allergen without adjuvant into
      mice caused an increase in total IgE Ab titers with a similar time course in the
      serum. However, the stage of initiation of allergy varied from allergen to
      allergen. Submandibular lymph node cells from normal mice contained papain-, but
      not mite feces- or pollen-specific IgE+ cells and an i.n. injection of papain
      induced papain-specific IgE Abs in the serum. In contrast, one (i.n.) or two
      (i.n. and s.c) injections of mite feces induced neither mite feces-specific IgE+
      cells in the lymph nodes nor mite feces-specific IgE Abs in the serum. I.n.
      sensitization with cedar pollen induced cedar pollen-specific IgE+ small B cells
      in the lymph nodes on Day 10, when non-specific IgE Ab titers reached a peak in
      the serum, implying induction of related allergen-specific IgE+ small cells as
      well. In fact, a second (s.c.) injection of ragweed (or cedar) pollen into mice
      sensitized i.n. once with cedar (or ragweed) pollen, but not with mite feces,
      induced a large amount of ragweed (or cedar) pollen-specific IgE Abs in the
      serum. These results indicate that when firstly-sensitized non-specific IgE+
      small B cells in mouse lymph nodes include some secondly-sensitized allergen
      specific ones, mice produce IgE Abs specific for the secondly-injected allergen.

PMID- 29193291
TI  - Validity and reliability of a Portuguese version of the Summated Xerostomia
      Inventory-5.
AB  - OBJECTIVES: The aim of this study was to validate and determine the reliability
      of the Portuguese version of the Summated Xerostomia Inventory. BACKGROUND: Many
      conditions such as head and neck radiation, autoimmune diseases or polypharmacy
      are characterised by hyposalivation which can affect oral and systemic quality of
      life. As such, this condition must be assessed, and the English version of the
      Xerostomia Inventory has been increasingly used to determine the severity of dry
      mouth perception. MATERIALS AND METHODS: This was a descriptive cross-sectional
      study, which employed volunteers suffering from hyposalivation after local
      ethical committee clearance. Each patient signed an informed consent and
      responded to the Portuguese version of the questionnaire in the form of an
      interview. This was repeated again after 2 weeks. A standard single question
      provided a validity check. Data were analysed using Cronbach's alpha to test its
      reliability and total and interitem correlation, and intraclass correlation to
      determine its internal consistency and test-retest reliability. Significance was
      set at .05. RESULTS: A sample of 103 volunteers was recruited. Cronbach's alpha
      was .84 and .87 for the first and second test administrations, respectively. The
      intraclass correlation coefficient value for the test-retest reliability was .93,
      and scores for the individual items ranged from .79 to .90. The correlation
      between the total score of the questionnaire and standard single dry mouth
      question was .66, indicating a very good correlation. CONCLUSION: Demonstrating
      excellent psychometric properties, the Summated Xerostomia Inventory (Portuguese
      Version) is a valid tool for quantifying Xerostomia in a dry mouth-afflicted
      population.

PMID- 29193292
TI  - A multispecies test of source-sink indicators to prioritize habitat for declining
      populations.
AB  - For species at risk of decline or extinction in source-sink systems, sources are
      an obvious target for habitat protection actions. However, the way in which
      source habitats are identified and prioritized can reduce the effectiveness of
      conservation actions. Although sources and sinks are conceptually defined using
      both demographic and movement criteria, simplifications are often required in
      systems with limited data. To assess the conservation outcomes of alternative
      source metrics and resulting prioritizations, we simulated population dynamics
      and extinction risk for 3 endangered species. Using empirically based habitat
      population models, we linked habitat maps with measured site- or habitat-specific
      demographic conditions, movement abilities, and behaviors. We calculated source
      sink metrics over a range of periods of data collection and prioritized
      consistently high-output sources for conservation. We then tested whether
      prioritized patches identified the habitats that most affected persistence by
      removing them and measuring the population response. Conservation decisions based
      on different source-sink metrics and durations of data collection affected
      species persistence. Shorter time series obscured the ability of metrics to
      identify influential habitats, particularly in temporally variable and slowly
      declining populations. Data-rich source-sink metrics that included both
      demography and movement information did not always identify the habitats with the
      greatest influence on extinction risk. In some declining populations, patch
      abundance better predicted influential habitats for short-term regional
      persistence. Because source-sink metrics (i.e., births minus deaths; births and
      immigrations minus deaths and emigration) describe net population conditions and
      cancel out gross population counts, they may not adequately identify influential
      habitats in declining populations. For many nonequilibrium populations, new
      metrics that maintain the counts of individual births, deaths, and movement may
      provide additional insight into habitats that most influence persistence.

PMID- 29193294
TI  - Posttraumatic Stress Disorder and Somatic Complaints in a Deployed Cohort of
      Georgian Military Personnel: Mediating Effect of Depression and Anxiety.
AB  - Several studies have shown the relationship between symptoms of posttraumatic
      stress disorder (PTSD), somatic symptoms, and the mediating effect of depression
      and anxiety. The following study was conducted to investigate the relationship
      between PTSD symptoms and somatic complaints through underlying symptoms of
      depression and anxiety. The participants of the study were 2,799 veterans who
      were examined after a 6-month deployment. They were assessed using the PTSD
      Checklist (PCL-5) and Patient Health Questionnaire (PHQ) for depression, anxiety,
      and somatic complaints. To check the indirect effect of PTSD on somatic
      complaints through depression and anxiety, mediation model 4 (parallel mediation)
      of the SPSS PROCESS macro was used. There was a significant total indirect effect
      of PTSD through depression and anxiety on somatic complaints, b = 0.14, 95%
      confidence interval (CI) [0.12, 0.16], from which an indirect effect of PTSD on
      somatic complaints through depression was b = 0.08, 95% CI [0.06, 0.10], and
      through anxiety it equaled b = 0.06, 95% CI [0.04, 0.07]. The ratio of indirect
      to total effect was 0.66, 95% CI [0.59, 0.75]. The present study helps us to
      understand the role of depression and anxiety symptoms when the symptoms of PTSD
      and somatic complaints are present. These new findings may have implications for
      the management as well as treatment of PTSD because they recognize the importance
      of symptoms of anxiety and depression when somatic complaints are present.

PMID- 29193295
TI  - What's in a word? The need for SIRS and sepsis definitions in equine medicine and
      surgery.

PMID- 29193293
TI  - Functional antagonism of sphingosine-1-phosphate receptor 1 prevents cuprizone
      induced demyelination.
AB  - Recent evidence suggests that the oral drug Fingolimod (FTY720) for relapsing
      remitting multiple sclerosis (MS) may act directly on the central nervous system
      (CNS) and modulate disease pathogenesis and progression in experimental models of
      MS. However, the specific subtype of sphingosine-1-phosphate (S1P) receptors that
      mediates the effect of FTY720 on the CNS cells has not been fully elucidated.
      Here, we report that S1P receptor 1 (S1PR1) is elevated in reactive astrocytes in
      an autoimmunity independent mouse model of MS and that selective S1PR1 modulation
      is sufficient to ameliorate the loss of oligodendrocytes and demyelination. The
      non-selective S1PR modulator, FTY720, or a short-lived S1PR1-specific modulator,
      CYM5442, was administered daily to mice while on cuprizone diet. Both FTY720- and
      CYM5422-treated mice displayed a significant reduction in oligodendrocyte
      apoptosis and astrocyte and microglial activation in comparison to vehicle
      treated groups, which was associated with decreased production of proinflammatory
      mediators and down-regulation of astrocytic S1PR1 protein. Interestingly, S1PR1
      modulation during the early phase of cuprizone intoxication was required to
      suppress oligodendrocyte death and consequent demyelination as drug treatment
      from 10 days after the initiation of cuprizone feeding was no longer effective.
      CYM5442 treatment during the brief cuprizone exposure significantly prevented Il
      1beta, Il-6, Cxcl10, and Cxcl3 induction, resulting in suppression of subsequent
      reactive gliosis and demyelination. Our study identifies functional antagonism of
      S1PR1 as a major mechanism for the protective effect of FTY720 in the cuprizone
      model and suggests pathogenic contributions of astrocyte S1PR1 signaling in
      primary demyelination and its potential as a therapeutic target for CNS
      inflammation.

PMID- 29193297
TI  - Peer reviewers in 2017.

PMID- 29193296
TI  - Peer review: Credit where credit is due.

PMID- 29193298
TI  - What Aspects of Rural Life Contribute to Rural-Urban Health Disparities in Older
      Adults? Evidence From a National Survey.
AB  - PURPOSE: Rural-urban health disparities are well-documented and particularly
      problematic for older adults. However, determining which specific aspects of
      rural or urban living initiate these disparities remains unclear. The purpose of
      this study was to assess associations between place-based characteristics of
      rural-urban status and health among adults age 65+. METHODS: Data from the 2012
      Behavioral Risk Factor Surveillance System were geographically linked to place
      based characteristics from the American Community Survey. Self-reported health
      (SRH), obesity, and health checkup within the last year were modeled against
      rural-urban status (distance to nearest metropolitan area, population size,
      population density, percent urban, Urban Influence Codes [UIC], Rural-Urban
      Continuum Codes [RUCC], and Rural-Urban Commuting Area [RUCA]) using generalized
      linear models, accounting for covariates and complex sampling, overall, and
      stratified by area-level income. FINDINGS: In general, increasing urbanicity was
      associated with a reduction in negative SRH for all 7 measures of rural-urban
      status. For low-income counties, this association held for all measures and
      characteristics of rural-urban status except population density. However, for
      high-income counties, the association was reversed-respondents living in areas of
      increasing urbanicity were more likely to report negative SRH for 4 of the 7
      measures (RUCC, UIC, RUCA, and percent urban). Findings were mixed for the
      outcome of obesity, where rural areas had higher levels, except in low-income
      counties, where the association between rurality and obesity was reversed (OR
      1.033, 95%CI: 1.002-1.064). CONCLUSION: These results suggest that rural-urban
      status is both a continuum and multidimensional. Distinct elements of rural-urban
      status may influence health in nuanced ways that require additional exploration
      in future studies.

PMID- 29193299
TI  - Improved parallel image reconstruction using feature refinement.
AB  - PURPOSE: The aim of this study was to develop a novel feature refinement MR
      reconstruction method from highly undersampled multichannel acquisitions for
      improving the image quality and preserve more detail information. THEORY AND
      METHODS: The feature refinement technique, which uses a feature descriptor to
      pick up useful features from residual image discarded by sparsity constrains, is
      applied to preserve the details of the image in compressed sensing and parallel
      imaging in MRI (CS-pMRI). The texture descriptor and structure descriptor
      recognizing different types of features are required for forming the feature
      descriptor. Feasibility of the feature refinement was validated using three
      different multicoil reconstruction methods on in vivo data. RESULTS: Experimental
      results show that reconstruction methods with feature refinement improve the
      quality of reconstructed image and restore the image details more accurately than
      the original methods, which is also verified by the lower values of the root mean
      square error and high frequency error norm. CONCLUSION: A simple and effective
      way to preserve more useful detailed information in CS-pMRI is proposed. This
      technique can effectively improve the reconstruction quality and has superior
      performance in terms of detail preservation compared with the original version
      without feature refinement. Magn Reson Med 80:211-223, 2018. (c) 2017
      International Society for Magnetic Resonance in Medicine.

PMID- 29193300
TI  - RNA interference-mediated knockdown and virus-induced suppression of Troponin C
      gene adversely affect the behavior or fitness of the green rice leafhopper,
      Nephotettix cincticeps.
AB  - The green rice leafhopper, Nephotettix cincticeps, is a major rice pest in
      Southeast Asia and Southern China. Novel control strategies must be explored to
      control the rice pest. Behavior or fitness regulation of insect by modulating the
      Troponin C (TnC) may be a novel strategy in the comprehensive management of the
      insect pest. However, characterizations and functions of TnC, especially
      regarding effect of its RNA interference-mediated gene knockdown on the behavior
      or fitness of N. cincticeps remain unknown. Here, we successfully cloned and
      characterized TnC gene from N. cincticeps (Nc-TnC). We demonstrated that Nc-TnC
      ubiquitously transcribed at all development stages and special tissues in adult
      insects, with relative higher levels at the adult stage and in the intestinal
      canal. Microinjection- or oral membrane feeding-based transient knockdown of Nc
      TnC adversely affected the performance or fitness, such as the decreased
      survival, feeding capacity, weight, and fecundity of N. cincticeps. Furthermore,
      we revealed that the expression of Nc-TnC was suppressed by its interaction with
      rice dwarf virus-encoded nonstructural protein 10, which ultimately affected
      detrimentally the corresponding parameters of the performance or fitness of N.
      cincticeps. In conclusion, our data deepen understanding of Nc-TnC functions
      during the development of and viral infection in N. cincticeps. It imply Nc-TnC
      may serve as a potential target for N. cincticeps control in future.

PMID- 29193301
TI  - Exposure to human voices has beneficial effects on preterm infants in the
      neonatal intensive care unit.
AB  - : We reviewed the literature up to March 2016 on the effects of nonmaternal
      voices on preterm infants' clinical outcomes. Of the 11 studies that met the
      inclusion criteria, 10 focused on short-term outcomes and one looked at long-term
      effects. The studies mainly showed that vocal stimuli increased preterm infants'
      stability in terms of heart rate, respiratory rate, oxygen saturation and
      behavioural measures. Improvements in feeding skills were also reported. The
      methods and the measures used in the studies were heterogeneous, making it
      difficult to draw reliable conclusions. CONCLUSION: Vocal stimuli increased
      preterm infants' stability, but further studies are needed.

PMID- 29193302
TI  - Enteroendocrine and adipokine associations with type 2 diabetes: Phenotypic risk
      scoring approaches.
AB  - BACKGROUND AND AIM: The contribution of gut-derived factors to the mechanisms
      linking obesity and metabolic disease remains under-investigated. The aim of the
      current study was to examine the associations between glucagon and
      enteroendocrine signaling and type 2 diabetes (T2D) using a derived risk score
      approach. To compare the relative importance of the enteroendocrine system,
      associations between adipokine measures and T2D were also investigated. METHODS:
      A total of 130 individuals with T2D and 161 individuals without T2D were included
      in the study. Circulating concentrations of enteroendocrine (glucagon, ghrelin,
      glucagon-like peptide-1, and gastric inhibitory peptide) and adipokine mediators
      (adiponectin, leptin, resistin, visfatin, and adipsin) were measured. Standard
      scores (Z-scores) were determined for each measure and enteroendocrine risk
      scores (ERS) and adipokine risk scores (ARS) calculated based on summation of the
      component measures. Associations between both the ERS and ARS and T2D status were
      assessed using logistic regression models. RESULTS: The ERS was significantly
      associated with T2D status in an adjusted model (odds ratio: 1.36; 95% confidence
      interval [CI]: 1.08-1.72; P = 0.009). Associations between the ARS and T2D status
      were not independent of age, sex, and body mass index (odds ratio: 1.21; 95%CI:
      0.99-1.47; P = 0.06). Quantification of risk across ERS tertiles revealed that
      individuals with an ERS in the upper tertile were 10 times more likely (CI: 3.23
      32.73; P < 0.001) to have T2D. CONCLUSIONS: These data support an association
      between enteroendocrine signaling and T2D. Use of the ERS as a potential tool for
      classifying individuals with metabolic syndrome as high or low risk for T2D
      development is being considered.

PMID- 29193303
TI  - Diagnosis, treatment and outcome of cranial nuchal bursitis in 30 horses.
AB  - BACKGROUND: No large retrospective case series describing the treatment and
      outcomes following diagnosis of cranial nuchal bursitis have been published.
      OBJECTIVE: To describe the clinical presentation, diagnostic techniques,
      treatment and outcome of horses suffering from cranial nuchal bursitis and to
      determine their outcome after medical or surgical treatment. STUDY DESIGN:
      Retrospective case series. METHODS: Medical records (1990-2014) of two referral
      centres were reviewed for signalment, diagnostic features, method of treatment
      (medical, surgical or both) and outcome. RESULTS: The median age of horses was 13
      years (range 5-22 years) and follow-up time ranged from 12 to 108 months.
      Fourteen horses were treated medically and 20 horses were treated surgically. Of
      those horses treated medically, four horses had recurrence of clinical signs
      requiring subsequent surgical treatment. Overall, 41.7% of horses had recurrence
      of clinical signs following treatment and 66.7% of horses were able to return to
      their previous level of exercise. Five horses underwent more than one surgical
      procedure due to recurrence of clinical signs. Of those horses treated solely
      surgically, 28.6% of the horses had recurrence of clinical signs and 78.6%
      returned to their previous level of exercise. Of those horses treated solely
      medically, 33.3% had recurrence of clinical signs and 66.7% returned to their
      previous level of exercise. Of those horses treated surgically following failed
      medical management, 100% had recurrence of clinical signs and 25% returned to
      their previous level of exercise. MAIN LIMITATIONS: Retrospective design with
      small sample number. CONCLUSIONS: Nuchal bursitis can be successfully managed
      with either medical or surgical treatment. Prognosis for return to work tends to
      be worse in horses requiring surgical intervention following failed medical
      management.

PMID- 29193304
TI  - Microbial colonization of the periodontal pocket and its significance for
      periodontal therapy.
AB  - The aim of this paper was to evaluate strategies for periodontal therapy from the
      perspective of periodontal disease being a consequence of microbial colonization
      of the periodontal pocket environment. In classic bacterial infections the
      diversity of the microbiota decreases as the disease develops. In most cases of
      periodontitis, however, the diversity of the flora increases. Most incriminating
      bacteria are thought to harm tissues significantly only if present in high
      numbers over prolonged periods of time. Clinical trials have repeatedly
      demonstrated that scaling and root planing, a procedure that aims to remove
      subgingival bacterial deposits by scraping on the tooth surface within the
      periodontal pocket, is effective. At present, for the therapy of any form of
      periodontal disease, there exists no protocol with proven superiority, in terms
      of efficiency or effectiveness, over scaling and root planing plus systemic
      amoxicillin and metronidazole. Some exponents advocate rationing these drugs for
      patients with a specific microbial profile. However, the evidence for any benefit
      of bacteriology-assisted clinical protocols is unsatisfactory. Treated sites are
      subject to recolonization with a microbiota similar to that present before
      therapy. The degree and speed of recolonization depends on the treatment
      protocol, the distribution patterns of periodontal microorganisms elsewhere in
      the oral cavity and the quality of the patient's oral hygiene. To limit the use
      of antibiotics and to avoid accumulation of harmful effects by repeated therapy,
      further efforts must be made to optimize procedures addressing the microbial
      colonization and recolonization of the periodontal pocket.

PMID- 29193305
TI  - The genetically determined production of the alarmin eosinophil-derived
      neurotoxin is reduced in visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. Recent
      findings indicate that dendritic cells have a key role in the defense against the
      Leishmania parasite and that the activity of this cell may be modified by the
      eosinophil secretory protein eosinophil-derived neurotoxin (EDN). We hypothesized
      that the interactions between dendritic cells and EDN might be of importance in
      the disease development. Cellular content of EDN was analyzed by ELISA. The
      single-nucleotide polymorphisms at positions 405, 416, and 1122 in the EDN gene
      were analyzed by real-time PCR with TaqMan(r) reagents. The study cohorts
      comprised 239 Sudanese subjects (65 healthy controls and 174 with VL) and 300
      healthy Swedish controls. The eosinophil content of EDN was lower in VL as
      compared with controls (p < 0.0001). The EDN405 (G>C) genotype distribution was
      similar among Swedish and Sudanese controls, whereas VL subjects had a higher
      prevalence of the EDN405-GG genotype (p < 0.0001). The content of EDN in the
      eosinophils was closely linked to the EDN405 polymorphism (p = 0.0002). Our
      findings suggest that the predisposition to acquire VL is related to the genetic
      polymorphism of the EDN gene and the reduced production by the eosinophil of this
      gene product.

PMID- 29193306
TI  - Artificial neural networks for stiffness estimation in magnetic resonance
      elastography.
AB  - PURPOSE: To investigate the feasibility of using artificial neural networks to
      estimate stiffness from MR elastography (MRE) data. METHODS: Artificial neural
      networks were fit using model-based training patterns to estimate stiffness from
      images of displacement using a patch size of ~1 cm in each dimension. These
      neural network inversions (NNIs) were then evaluated in a set of simulation
      experiments designed to investigate the effects of wave interference and noise on
      NNI accuracy. NNI was also tested in vivo, comparing NNI results against
      currently used methods. RESULTS: In 4 simulation experiments, NNI performed as
      well or better than direct inversion (DI) for predicting the known stiffness of
      the data. Summary NNI results were also shown to be significantly correlated with
      DI results in the liver (R2  = 0.974) and in the brain (R2  = 0.915), and also
      correlated with established biological effects including fibrosis stage in the
      liver and age in the brain. Finally, repeatability error was lower in the brain
      using NNI compared to DI, and voxel-wise modeling using NNI stiffness maps
      detected larger effects than using DI maps with similar levels of smoothing.
      CONCLUSION: Artificial neural networks represent a new approach to inversion of
      MRE data. Summary results from NNI and DI are highly correlated and both are
      capable of detecting biologically relevant signals. Preliminary evidence suggests
      that NNI stiffness estimates may be more resistant to noise than an algebraic DI
      approach. Taken together, these results merit future investigation into NNIs to
      improve the estimation of stiffness in small regions. Magn Reson Med 80:351-360,
      2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 29193307
TI  - Approaching ultimate intrinsic specific absorption rate in radiofrequency
      shimming using high-permittivity materials at 7 Tesla.
AB  - PURPOSE: The aim of this study was to evaluate the effect of integrated high
      permittivity materials (HPMs) on excitation homogeneity and global specific
      absorption rate (SAR) for transmit arrays at 7T. METHODS: A rapid electrodynamic
      simulation framework was used to calculate L-curves associated with excitation of
      a uniform 2D profile in a dielectric sphere. We used ultimate intrinsic SAR as an
      absolute performance reference to compare different transmit arrays in the
      presence and absence of a layer of HPM. We investigated the optimal permittivity
      for the HPM as a function of its thickness, the sample size, and the number of
      array elements. RESULTS: Adding a layer of HPM can improve the performance of a
      24-element array to match that of a 48-element array without HPM, whereas a 48
      element array with HPM can perform as well as a 64-element array without HPM.
      Optimal relative permittivity values changed based on sample and coil geometry,
      but were always within a range obtainable with readily available materials
      (epsilonr  = 100-200). CONCLUSION: Integration of HPMs could be a practical
      method to improve RF shimming performance, alternative to increasing the number
      of coils. The proposed simulation framework could be used to explore the design
      of novel transmit arrays for head imaging at ultra-high field strength. Magn
      Reson Med 80:391-399, 2018. (c) 2017 International Society for Magnetic Resonance
      in Medicine.

PMID- 29193308
TI  - The Influence of Chronic Kidney Disease on the Structural and Mechanical
      Properties of Canine Bone.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common in companion animals.
      Secondary hyperparathyroidism is an inevitable consequence of the disease and may
      have deleterious effect on the bone; however, the information regarding CKD
      associated bone abnormalities in companion animals is scarce.
      HYPOTHESIS/OBJECTIVES: Dogs with CKD have decreased bone quality compared to dogs
      without CKD. ANIMALS: Nine dogs diagnosed with naturally occurring CKD for at
      least 6 months and 9 age-matched controls. METHODS: Dogs with CKD were enrolled
      and compared to 9 age-, weight-, and sex-matched control dogs with no evidence of
      CKD. Samples were assessed using light microscopy, mechanical testing, and
      microcomputed tomography. Variables evaluated included microstructural features
      such as number, size, and density of Haversian canals, resorption cavities and
      osteocytic lacunae, bone mineral density, porosity and Young's modulus. RESULTS:
      Median lacunae size was significantly smaller in the CKD group compared to the
      control group (P = 0.001). Resorption cavity density was higher in the CKD
      compared to the control group (10 [8-14] vs. 7 [4-9]/mm2 , respectively, P =
      0.001). Overall porosity was significantly (2.3-fold) higher in the CKD compared
      to the control group. There was no difference in Young's moduli between groups.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Naturally occurring CKD affects bone quality
      in dogs, but these changes are relatively mild and likely not to be manifested
      clinically. The duration of the disease in dogs evaluated here is short compared
      to cats and human patients, likely accounting for the more subtle changes in dogs
      compared to other species.

PMID- 29193310
TI  - Bacterial modulators of bone remodeling in the periodontal pocket.
AB  - The signaling network involved in the pathogenesis of periodontal disease is not
      yet fully understood. This review aims to describe possible mechanisms through
      which the bacterial modulators may be linked directly or indirectly to the
      process of alveolar bone loss in periodontitis. From the late 1970s to present,
      new paradigm shifts have been developed regarding our understanding of
      pathological bone remodeling in periodontal disease. Upcoming evidence suggests
      that in periodontal disease the local immune response is exacerbated and involves
      the existence of signaling pathways that have been shown to modulate bone-cell
      function leading to alveolar bone loss. Those complex signaling pathways have
      been observed not only between bacteria but also between bacteria and the
      gingival surface of the host. More specifically, it has been shown that bacteria,
      through their secretion molecules, may interact indirectly and directly with
      immune-type cells of the host, resulting in the production of osteolytic agents
      that enhance bone resorption. Further research is required to provide a clear
      understanding of the role of these molecules in the pathogenesis of periodontal
      disease, and the availability of new technologies, such as next-generation
      sequencing and metagenomic analysis, may be useful tools in achieving this.

PMID- 29193311
TI  - Proteomics analysis of human breast milk to assess breast cancer risk.
AB  - Detection of breast cancer (BC) in young women is challenging because
      mammography, the most common tool for detecting BC, is not effective on the dense
      breast tissue characteristic of young women. In addition to the limited means for
      detecting their BC, young women face a transient increased risk of pregnancy
      associated BC. As a consequence, reproductively active women could benefit
      significantly from a tool that provides them with accurate risk assessment and
      early detection of BC. One potential method for detection of BC is biochemical
      monitoring of proteins and other molecules in bodily fluids such as serum, nipple
      aspirate, ductal lavage, tear, urine, saliva and breast milk. Of all these
      fluids, only breast milk provides access to a large volume of breast tissue, in
      the form of exfoliated epithelial cells, and to the local breast environment, in
      the form of molecules in the milk. Thus, analysis of breast milk is a non
      invasive method with significant potential for assessing BC risk. Here we
      analyzed human breast milk by mass spectrometry (MS)-based proteomics to build a
      biomarker signature for early detection of BC. Ten milk samples from eight women
      provided five paired-groups (cancer versus control) for analysis of
      dysregulatedproteins: two within woman comparisons (milk from a diseased breast
      versus a healthy breast of the same woman) and three across women comparisons
      (milk from a woman with cancer versus a woman without cancer). Despite a wide
      range in the time between milk donation and cancer diagnosis (cancer diagnosis
      occurred from 1 month before to 24 months after milk donation), the levels of
      some proteins differed significantly between cancer and control in several of the
      five comparison groups. These pilot data are supportive of the idea that
      molecular analysis of breast milk will identify proteins informative for early
      detection and accurate assessment of BC risk, and warrant further research. Data
      are available via ProteomeXchange with identifier PXD007066.

PMID- 29193312
TI  - Understanding Age-Induced Cortical Porosity in Women: The Accumulation and
      Coalescence of Eroded Cavities Upon Existing Intracortical Canals Is the Main
      Contributor.
AB  - Intracortical bone remodeling normally ensures maintenance of the cortical bone
      matrix and strength, but during aging, this remodeling generates excessive
      porosity. The mechanism behind the age-induced cortical porosity is poorly
      understood and addressed in the present study. This study consists of a
      histomorphometric analysis of sections of iliac bone specimens from 35 women (age
      16-78 years). First, the study shows that the age-induced cortical porosity
      reflects an increased pore size rather than an increased pore density. Second, it
      establishes a novel histomorphometric classification of the pores, which is based
      on the characteristics of the remodeling sites to which each pore is associated.
      It takes into consideration (i) the stage of the remodeling event at the level
      where the pore is sectioned, (ii) whether the event corresponds with the
      generation of a new pore through penetrative tunneling (type 1 pores) or with
      remodeling of an existing pore (type 2 pores), and (iii) in the latter case,
      whether or not the new remodeling event leads to the coalescence of pores. Of
      note, the advantage of this classification is to relate porosity with its
      generation mechanism. Third, it demonstrates that aging and porosity are
      correlated with: a shift from type 1 to type 2 pores, reflecting that the
      remodeling of existing pores is higher; an accumulation of eroded type 2 pores,
      reflecting an extended resorption-reversal phase; and a coalescence of these
      eroded type 2 pores into enlarged coalescing type 2 cavities. Collectively, this
      study supports the notion, that age-related increase in cortical porosity is the
      result of intracortical remodeling sites upon existing pores, with an extended
      reversal-resorption phase (eroded type 2 pores) that may likely result in a
      delayed or absent initiation of the subsequent bone formation. (c) 2017 The
      Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

PMID- 29193309
TI  - Converging early responses to brain injury pave the road to epileptogenesis.
AB  - Epilepsy, characterized by recurrent seizures and abnormal electrical activity in
      the brain, is one of the most prevalent brain disorders. Over two million people
      in the United States have been diagnosed with epilepsy and 3% of the general
      population will be diagnosed with it at some point in their lives. While most
      developmental epilepsies occur due to genetic predisposition, a class of
      "acquired" epilepsies results from a variety of brain insults. A leading
      etiological factor for epilepsy that is currently on the rise is traumatic brain
      injury (TBI), which accounts for up to 20% of all symptomatic epilepsies.
      Remarkably, the presence of an identified early insult that constitutes a risk
      for development of epilepsy provides a therapeutic window in which the
      pathological processes associated with brain injury can be manipulated to limit
      the subsequent development of recurrent seizure activity and epilepsy. Recent
      studies have revealed diverse pathologies, including enhanced excitability,
      activated immune signaling, cell death, and enhanced neurogenesis within a week
      after injury, suggesting a period of heightened adaptive and maladaptive
      plasticity. An integrated understanding of these processes and their cellular and
      molecular underpinnings could lead to novel targets to arrest epileptogenesis
      after trauma. This review attempts to highlight and relate the diverse early
      changes after trauma and their role in development of epilepsy and suggests
      potential strategies to limit neurological complications in the injured brain.

PMID- 29193313
TI  - Estimating the number of potential family members eligible for BRCA1 and BRCA2
      mutation testing in a "Traceback" approach.
AB  - U.S. guidelines recommend BRCA1/2 mutation testing for women diagnosed with high
      grade ovarian cancer (HGOC) to increase recognition of carriers, but most remain
      unidentified and at risk. Accordingly, an approach termed "Traceback" has been
      proposed in which probands are retrospectively identified by testing archived
      pathology specimens, and family members are traced to provide genetic counseling
      and testing. We used population-based data to estimate the number of family
      members who might be contacted through such a program. We used incidence data
      from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate
      the number of women diagnosed with HGOC from 2005 to 2016, and census data to
      estimate the number of spouses, offspring, and siblings (both sexes). Using
      overall survival for HGOC from SEER and all-cause mortality rates from the
      Centers for Diseases Control and Prevention, we estimated the number of patients,
      spouses, offspring, and siblings of HGOC cases living in 2017. Due to the high
      mortality rate of HGOC, consent from living probands may be possible in only 42%
      of the cases; consent to test pathology specimens would need to be sought from
      next of kin for the remainder. In 2017, an estimated 406,919 living next of kin
      (spouses, siblings, offspring) would be available for potential consent. Testing
      archived ovarian cancer pathology specimens may enable the identification of
      BRCA1/2 mutation carriers, but consent from next of kin would be required in in
      58% of cases. Although Traceback offers the possibility of identifying unaffected
      BRCA1/2 mutation carriers, pilot feasibility studies that include assessment of
      methods to secure consent are needed.

PMID- 29193314
TI  - Effects of wobble board training on single-leg landing neuromechanics.
AB  - Balance training programs have been shown to reduce ankle sprain injuries in
      sports, but little is known about the transfer from this training modality to
      motor coordination and ankle joint biomechanics in sport-specific movements. This
      study aimed to investigate the effects of wobble board training on motor
      coordination and ankle mechanics during early single-leg landing from a lateral
      jump. Twenty-two healthy men were randomly assigned to either a control or a
      training group, who engaged in 4 weeks of wobble board training. Full-body
      kinematics, ground reaction force, and surface electromyography (EMG) from 12
      lower limb muscles were recorded during landing. Ankle joint work in the
      sagittal, frontal, and transverse plane was calculated from 0 to 100 ms after
      landing. Non-negative matrix factorization (NMF) was applied on the concatenated
      EMG Pre- and Post-intervention. Wobble board training increased the ankle joint
      eccentric work 1.2 times in the frontal (P < .01) and 4.4 times in the transverse
      plane (P < .01) for trained participants. Wobble board training modified the
      modular organization of muscle recruitment in the early landing phase by
      separating the activation of plantar flexors and mediolateral ankle stabilizers.
      Furthermore, the activation of secondary muscles across motor modules was reduced
      after training, refocusing the activation on the main muscles involved in the
      mechanical main subfunctions for each module. These results suggest that wobble
      board training may modify motor coordination when landing from a lateral jump,
      focusing on the recruitment of specific muscles/muscle groups that optimize ankle
      joint stability during early ground contact in single-leg landing.

PMID- 29193315
TI  - Review shows that implementing a nationwide protocol for congenital diaphragmatic
      hernia was a key factor in reducing mortality and morbidity.
AB  - : The French Rare Disease Reference Center for congenital diaphragmatic hernia
      (CDH) was created in 2008, to implement a national protocol for foetuses and
      children with this serious condition. Neonatal mortality from CDH is 30-40%,
      mainly due to pulmonary hypoplasia and persistent pulmonary hypertension, and
      half of those who live have high respiratory, nutritional and digestive
      morbidity. CDH management requires long-term and specialised multidisciplinary
      care. It has been well established that a standardised management protocol
      improves the prognosis of children with CDH. CONCLUSION: Organising health care
      and implementing a nationwide French protocol were key factors for reducing
      mortality and morbidity from CDH.

PMID- 29193316
TI  - Posttraumatic Stress Symptom Trajectories Among Children After Disaster Exposure:
      A Review.
AB  - Natural disasters, such as hurricanes and floods, are increasing in frequency and
      scope. Youth exposed to disasters are at risk for developing posttraumatic stress
      symptoms (PTSS). However, not all youth who report initially elevated PTSS report
      persistent PTSS that last beyond the first three to six months postdisaster.
      Thus, it is crucial to understand how and why youth differ in their patterns of
      PTSS. This study reviewed the literature on children's postdisaster PTSS,
      evaluating the typical number and types of patterns for children's PTSS
      trajectories, as well as risk and protective factors predicting trajectory
      membership. This review identified eight empirical studies on youth PTSS
      trajectories following natural disasters; these studies included 8,306 children
      aged 3 to 18 years. All studies identified resilience, recovery, and chronic
      trajectories. Evidence for a delayed trajectory was mixed. Proportions of
      children falling into each trajectory varied widely across studies, but overall,
      resilience was the most prevalent trajectory. These findings were consistent
      across study factors (i.e., analytic strategy, assessment timing, and study
      selection criteria). Female gender, disaster exposure, negative coping, and lack
      of social support were significant risk factors for chronic trajectories across
      several studies. Future research should combine individual level participant data
      across studies of children's responses to disasters to better understand PTSS
      trajectories.

PMID- 29193317
TI  - Addressing the wicked problem of childhood trauma through a nursing and
      cooperative extension system collaboration.
AB  - The purpose of this clinical concept report is to describe a public health
      project in rural Indiana that addressed the complex social issue or "wicked
      problem" of childhood trauma. The project was implemented through a unique
      partnership between nursing faculty and Cooperative Extension Educators,
      community-based workers who are associated with fulfilling the mission of Land
      Grant Universities. The core focus of the project entailed a nurse and a
      Cooperative Extension Educator co-teaching trauma-informed parenting classes to
      rural dwelling, kinship caregivers. Kinship caregivers are often grandparents who
      assume the parenting role after the child has been removed from the birth
      parents' care. The trauma-informed curriculum was developed by experts in child
      trauma and is available through the National Child Traumatic Stress Network. The
      unique partnership provided insight into the different missions of the two
      organizations, different values and workflow metrics, and different schedules,
      which at times proved to be barriers to implementation. This discussion focuses
      on deconstructing the goals and objectives of the project and retrospectively,
      describing recommendations so that public health nurses may partner with
      Extension Educators in their communities for optimal project success.

PMID- 29193318
TI  - Editorial: Stop thinking and start acting: Early Impella placement associated
      with improved outcomes, again!

PMID- 29193319
TI  - Editorial: The "JET" technique for provisional side-branch stenting back to the
      future, and in the right direction.

PMID- 29193320
TI  - Contrast-balanced binocular treatment in children with deprivation amblyopia.
AB  - BACKGROUND: Children with deprivation amblyopia due to childhood cataract have
      been excluded from much of the emerging research into amblyopia treatment. An
      investigation was conducted to determine whether contrast-balanced binocular
      treatment - a strategy currently being explored for children with anisometropic
      and strabismic amblyopia - may be effective in children with deprivation
      amblyopia. METHODS: An unmasked, case-series design intended to assess proof of
      principle was employed. Eighteen children with deprivation amblyopia due to
      childhood cataracts (early bilateral n = 7, early unilateral n = 7, developmental
      n = 4), as well as 10 children with anisometropic (n = 8) or mixed anisometropic
      and strabismic amblyopia (n = 2) were prescribed one hour a day of treatment over
      a six-week period. Supervised treatment was available. Visual acuity, contrast
      sensitivity, global motion perception and interocular suppression were measured
      pre- and post-treatment. RESULTS: Visual acuity improvements occurred in the
      anisometropic/strabismic group (0.15 +/- 0.05 logMAR, p = 0.014), but contrast
      sensitivity did not change. As a group, children with deprivation amblyopia had a
      smaller but statistically significant improvement in weaker eye visual acuity
      (0.09 +/- 0.03 logMAR, p = 0.004), as well a significant improvement in weaker
      eye contrast sensitivity (p = 0.004). Subgroup analysis suggested that the
      children with early bilateral deprivation had the largest improvements, while
      children with early unilateral cataract did not improve. Interestingly, binocular
      contrast sensitivity also improved in children with early bilateral deprivation.
      Global motion perception improved for both subgroups with early visual
      deprivation, as well as children with anisometropic or mixed
      anisometropic/strabismic amblyopia. Interocular suppression improved for all
      subgroups except children with early unilateral deprivation. CONCLUSION: These
      data suggest that supervised contrast-balanced binocular treatment should be
      further investigated as a treatment option for children with deprivation
      amblyopia. However, for children with more severe deprivation amblyopia due to
      early unilateral cataracts, supplementary or alternative options should also be
      explored.

PMID- 29193321
TI  - Predictors of early renal function decline in Type 1 diabetes: retinopathy.

PMID- 29193323
TI  - CCDC104 Antibodies and Mitosis of Cancer Cells.

PMID- 29193322
TI  - Vision screening at two years does not reduce the prevalence of reduced vision at
      four and a half years of age.
AB  - BACKGROUND: There is currently insufficient evidence to recommend vision
      screening for children < 36 months of age. This study assessed the effect of
      comprehensive vision screening, as well as the sensitivity of age-appropriate
      vision tests, at two years of age on habitual visual acuity at 4.5 years of age.
      METHODS: Children born at risk of neonatal hypoglycaemia (n = 477) underwent
      vision assessment at 54 +/- 2 months of age including measurement of monocular
      and binocular habitual visual acuity, assessment of binocularity and stereopsis.
      Of these children, 355 (74.4 per cent) had also received vision screening at two
      years of age (mean age = 24+/- 1 months), while 122 were not screened. RESULTS:
      Eighty (16.8 per cent) children were classified as having reduced vision at 4.5
      years of age, but the prevalence of reduced vision did not differ between
      children who had previously been screened at two years of age and those who had
      not (15.5 per cent versus 20.5 per cent, p = 0.153). However, children with
      reduced vision at 4.5 years of age were more likely to have had visual
      abnormalities requiring referral detected at two years of age (p = 0.02). Visual
      acuity and mean spherical equivalent autorefraction measurements were also worse
      (higher values) in two-year-old children who were later classified with reduced
      habitual visual acuity (p = 0.031 and p = 0.001, respectively). Nevertheless,
      unaided binocular visual acuity, non-cycloplegic refractive error, and stereopsis
      at two years all showed poor sensitivity and specificity for predicting visual
      outcomes at 4.5 years of age. CONCLUSION: Our findings do not support the
      adoption of early vision screening in children as current vision tests suitable
      for use with two-year-old children have poor sensitivity for predicting mild
      moderate habitual vision impairment at 4.5 years of age.

PMID- 29193324
TI  - A simple hand-held magnet array for efficient and reproducible SABRE
      hyperpolarisation using manual sample shaking.
AB  - Signal amplification by reversible exchange (SABRE) is a hyperpolarisation
      technique that catalytically transfers nuclear polarisation from parahydrogen,
      the singlet nuclear isomer of H2 , to a substrate in solution. The SABRE exchange
      reaction is carried out in a polarisation transfer field (PTF) of tens of gauss
      before transfer to a stronger magnetic field for nuclear magnetic resonance (NMR)
      detection. In the simplest implementation, polarisation transfer is achieved by
      shaking the sample in the stray field of a superconducting NMR magnet. Although
      convenient, this method suffers from limited reproducibility and cannot be used
      with NMR spectrometers that do not have appreciable stray fields, such as
      benchtop instruments. Here, we use a simple hand-held permanent magnet array to
      provide the necessary PTF during sample shaking. We find that the use of this
      array provides a 25% increase in SABRE enhancement over the stray field approach,
      while also providing improved reproducibility. Arrays with a range of PTFs were
      tested, and the PTF-dependent SABRE enhancements were found to be in excellent
      agreement with comparable experiments carried out using an automated flow system
      where an electromagnet is used to generate the PTF. We anticipate that this
      approach will improve the efficiency and reproducibility of SABRE experiments
      carried out using manual shaking and will be particularly useful for benchtop
      NMR, where a suitable stray field is not readily accessible. The ability to
      construct arrays with a range of PTFs will also enable the rapid optimisation of
      SABRE enhancement as function of PTF for new substrate and catalyst systems.

PMID- 29193325
TI  - Reappraisal of cortical myoclonus: A retrospective study of clinical
      neurophysiology.

PMID- 29193326
TI  - Tibiotarsus bone characteristics and tibial dyschondroplasia incidence of
      broilers fed diets supplemented with leucine and valine.
AB  - Two experiments were conducted to study the effect of standardized ileal
      digestible (SID) leucine and valine levels on tibiotarsus bone characteristics
      and the incidence of tibial dyschondroplasia of broilers from day 1 to 21
      (Experiment I) and day 21 to 42 post-hatch (Experiment II). Each experimental
      phase was evaluated independently. In both experiments, a total of 1,500 one-day
      old Cobb 500 male broiler chickens were distributed in a completely randomized
      design 5 * 5 factorial arrangement for a total of 25 treatments. The SID leucine
      and valine levels were ranged from 10.0 to 19.6 g/kg, and 6.0 to 12.0 g/kg from
      day 1 to 21 post-hatch, respectively, while day 21 to 42 post-hatch ranged from
      10.0 to 18.0 g leucine/kg, and 5.2 to 11.2 g valine/kg. Serum calcium and
      phosphorus, bone concentrations of calcium, phosphorus and ash, diameter and
      Seedor index of the tibiotarsus were not affected (p > .05) by the treatments at
      21 or 42 days of age. There was an interaction (p <=.06) between the SID levels
      of leucine and valine on tibiotarsus breaking strength at 21 days, but not at 42
      days of age (p > .05). Tibiotarsus breaking strength was maximized in broilers
      from day 1 to 21 with the dietary levels of leucine and valine at 14.2 and 9.0
      g/kg respectively. Dietary leucine levels reduced linearly (p < .05) the
      hypertrophic zone of tibiotarsus cartilage at 21 days of age. Therefore, leucine
      and valine supplementation interact positively on bone strength of broilers from
      day 1 to 21 post-hatch. Leucine can be a useful amino acid for reducing the
      hypertrophic cartilage zone in broilers from day 1 to 21, but not from day 21 to
      42 post-hatch.

PMID- 29193327
TI  - Effects of Toceranib Phosphate on the Hypothalamic-Pituitary-Thyroid Axis in
      Tumor-Bearing Dogs.
AB  - BACKGROUND: Thyroid dysfunction is associated with the use of tyrosine kinase
      inhibitors (TKI) in people. HYPOTHESIS/OBJECTIVES: To determine whether
      dysfunction in the hypothalamic-pituitary-thyroid axis occurs in dogs receiving
      the TKI, toceranib phosphate. ANIMALS: Forty-three client-owned dogs with cancer.
      METHODS: Prospective, observational study. Concentrations of total thyroxine
      (TT4), free thyroxine (FT4), total triiodothyronine (TT3), and thyroid
      stimulating hormone (TSH) were evaluated on day 0, 30, and 90. Dogs also were
      evaluated for the presence of thyroglobulin autoantibodies. RESULTS: The
      proportion of dogs with low TT4, low FT4, low TT3, high TSH, or primary
      hypothyroidism (increased TSH and decreased TT4, FT4 or both) did not change over
      90 days. Hormone concentrations remained within laboratory reference intervals,
      but FT4 (P = 0.0032) and TSH (P < 0.0001) changed over time. Mean FT4 was 1.22
      ng/dL (95% confidence interval [CI], 1.10-1.34) on day 0 and 1.00 ng/dL (95% CI,
      0.86-1.16) on day 90. Mean TSH was 0.17 ng/mL (95% CI, 0.13-0.23) on day 0 and
      0.34 ng/mL (95% CI, 0.24-0.48) on day 90. Furthermore, TT4/TT3 ratio also changed
      over time (P = 0.0086). Mean TT4/TT3 ratio was 2.57 (95% CI, 2.26-2.88) on day 0
      and 2.02 on day 90 (95% CI, 1.61-2.44). Thyroglobulin autoantibodies were not
      detected in any dog. CONCLUSIONS AND CLINICAL IMPORTANCE: Toceranib phosphate can
      disrupt the hypothalamic-pituitary-thyroid axis in dogs. Periodic evaluation of
      TT4, FT4, TT3, and TSH should be carried out in dogs receiving long-term
      treatment with this medication.

PMID- 29193328
TI  - Transport of valine across the small intestinal epithelium in pigs fed different
      valine levels and Bacillus subtilis.
AB  - Mutants of Bacillus subtilis overproducing valine (B. subtilis VAL) could be an
      approach to supply pigs dietary valine (Val). In the study, 18 gilts were fed:
      (i) negative diet with a standardized ileal digestible (SID) Val:Lys of 0.63:1
      (Neg); (ii) Neg added B. subtilis VAL (1.28 * 1011  cfu/kg as-fed) or; (iii) Neg
      added L-Val to a Val:Lys of 0.69:1. Using the Ussing chamber method, the study
      aimed to investigate whether (i) the diets affect intestinal transport of
      additions of 0, 5, 10 or 20 mmol Val/L from the mucosal to the serosal side and
      (ii) the B. subtilis VAL contributes to a net transport of Val produced in situ.
      The results showed that the Isc (DeltaIscVal ) and release of Val to the serosal
      side solution (Srel ; MUmol cm-2  min-1 ) increased with Val addition (linear and
      quadratic, p < .0001) but was similar for 5, 10 or 20 mmol Val/L and not affected
      by diet. No net transport of in situ produced Val by B. subtilis VAL was
      detected. In conclusion, feeding a Val-deficient diet with or without B. subtilis
      VAL or a Val sufficient diet did not affect the Val transport across intestinal
      epithelia. No in situ Val production by B. subtilis VAL was observed in the
      Ussing chambers.

PMID- 29193329
TI  - A few considerations on "Achilles and patellar tendinopathy display opposite
      changes in elastic properties".

PMID- 29193330
TI  - A DNA-Threaded ZIF-8 Membrane with High Proton Conductivity and Low Methanol
      Permeability.
AB  - Natural biomolecules have potential as proton-conducting materials, in which the
      hydrogen-bond networks can facilitate proton transportation. Herein, a
      biomolecule/metal-organic framework (MOF) approach to develop hybrid proton
      conductive membranes is reported. Single-strand DNA molecules are introduced into
      DNA@ZIF-8 membranes through a solid-confined conversion process. The DNA-threaded
      ZIF-8 membrane exhibits high proton conductivity of 3.40 * 10-4 S cm-1 at 25 
      degrees C and the highest one ever reported of 0.17 S cm-1 at 75  degrees C,
      under 97% relatively humidity, attributed to the formed hydrogen-bond networks
      between the DNA molecules and the water molecules inside the cavities of the ZIF
      8, but very low methanol permeability of 1.25 * 10-8 cm2 s-1 due to the small
      pore entrance of the DNA@ZIF-8 membranes. The selectivity of the DNA@ZIF-8
      membrane is thus significantly higher than that of developed proton-exchange
      membranes for fuel cells. After assembling the DNA@ZIF-8 hybrid membrane into
      direct methanol fuel cells, it exhibits a power density of 9.87 mW cm-2 . This is
      the first MOF-based proton-conductivity membrane used for direct methanol fuel
      cells, providing bright promise for such hybrid membranes in this application.

PMID- 29193331
TI  - Host modulation therapy with anti-inflammatory agents.
AB  - Host modulation therapy refers to a treatment concept in which drug therapies are
      used as an adjunct to conventional periodontal treatment to ameliorate
      destructive aspects of the host inflammatory response. This strategy is not new
      in the treatment of periodontitis. Previously, nonsteroidal anti-inflammatory
      drugs have been investigated in this regard, with evidence of reductions in
      alveolar bone resorption when these drugs are used for prolonged periods of time.
      However, the risk of significant unwanted effects precludes the use of both
      nonselective nonsteroidal anti-inflammatory drugs and the selective
      cyclooxygenase-2 inhibitors as adjunctive treatments for periodontitis.
      Currently, the only available adjunctive host response modulator that is licensed
      for the treatment of periodontitis is subantimicrobial dose doxycycline, which
      functions as an inhibitor of matrix metalloproteinases. Although clinical
      benefits have been shown in carefully conducted randomized controlled trials, the
      efficacy of subantimicrobial dose doxycycline in routine clinical practice has
      yet to be determined. Anti-cytokine therapies have been developed for use in the
      treatment of rheumatoid arthritis, the pathogenesis of which bears many
      similarities to that of periodontitis; however, the significant risk of unwanted
      effects (as well as cost and lack of human trials in the treatment of periodontal
      diseases) precludes the use of any of the currently available anti-cytokine
      therapies in the treatment of periodontitis. The identification of pro-resolving
      lipid mediators as well as small molecule biologicals that influence inflammatory
      responses offers the best potential, at the present time, for the development of
      novel host response modulators in periodontal therapy, but much research remains
      to be done to confirm safety and efficacy.

PMID- 29193332
TI  - Humidity-Responsive ON/OFF Switching of Gas Inclusion by Using Cooperative
      Opening/Closing of Heterogeneous Crystalline Cavities in a Peptide NiII
      Macrocycle.
AB  - Humidity-responsive ON/OFF switching of CO2 inclusion, associated with
      cooperative structural changes of heterogeneous cavities in crystalline peptide
      NiII macrocycles, 1?NO3 , is demonstrated. The structural transformation between
      an "open form" and a "closed form" was caused by reversible water uptake into one
      of the cavities. The adsorption behavior of CO2 was studied with and without
      water vapor, combined with gas-composition analysis by using gas chromatography.
      The studies revealed that the open form of 1?NO3 adsorbs CO2 gas up to 34 g mol-1
      , whereas the closed form adsorbs only a negligible amount of CO2 gas. Also,
      structural studies (X-ray and IR spectroscopies) and investigation of water
      content dependence of CO2 adsorption revealed that the switching of gas inclusion
      occurred abruptly over a narrow range of water-vapor pressure and was caused by
      the cooperative opening of vacant space to give the open form due to the
      structural transformation by water uptake.

PMID- 29193333
TI  - Repeated MitraClip procedure in patients with recurrent MR after a successful
      first procedure: Limitations and outcome.
AB  - OBJECTIVES: The present study aimed to evaluate the outcome and potential
      limitations of a repeated MitraClip procedure (ReClip). BACKGROUND: The MitraClip
      procedure has emerged as a treatment option in high surgical risk patients
      suffering from severe mitral regurgitation (MR). However, despite successful
      initial repair a significant number of patients develops severe recurrent MR.
      METHODS: Patients undergoing a ReClip procedure in our institution were
      retrospectively identified. Baseline data and the procedural outcome were
      assessed to identify potential limitations of such procedures. RESULTS: Fifteen
      out of 234 patients undergoing a mitral-valve repair with the MitraClip device
      (Abbott Vascular) underwent a ReClip due to recurrent MR. In 11 patients, a MR
      reduction of at least one degree without causing mitral valve stenosis (trans
      mitral mean gradient >=5 mmHg) was achieved by performing a ReClip. After 1 year,
      two patients developed severe recurrent MR again. Pulmonary artery pressures
      significantly decreased after the procedure in individuals with successful repair
      (MR reduction of at least one degree and mitral valve mean gradient <5 mmHg).
      CONCLUSION: A ReClip procedure may be feasible in patients with recurrent MR but
      the risk benefit ratio should be carefully balanced against other treatment
      options.

PMID- 29193334
TI  - Comparison of peri-implant and periodontal marginal soft tissues in health and
      disease.
AB  - The integrity of the peri-implant soft-tissue seal is crucial for maintaining
      peri-implant tissue health. Whilst the transmucosal component of the restored
      implant shares some common features with teeth, namely the presence of a
      junctional epithelium and a connective tissue component, there are some important
      differences. A key difference is the nature of the relationship of the connective
      tissue with the implant surface, whereby there is 'adaptation' of collagen fibers
      in a parallel orientation in relation to the implant, but insertion of fiber
      attachment perpendicularly into cementum in the case of teeth. This, combined
      with reduced cellularity and vascularity in the peri-implant connective tissue,
      may make implants more susceptible to disease initiation and progression.
      Furthermore, the presence of a subgingival connection between the implant and the
      abutment/restoration poses some specific challenges, and maintaining the
      integrity of this connection is important in preserving peri-implant tissue
      health. Implant design features, such as the nature of the connection between the
      implant and the abutment, as well as the surface characteristics of the abutment
      and implants, may influence the maintenance of the integrity of soft tissue
      around implants. Iatrogenic factors, such as incorrect seating of the abutment
      and/or the restoration, and the presence of residual subgingival cement, will
      lead to loss of soft-tissue integrity and hence predispose to peri-implant
      disease.

PMID- 29193335
TI  - C9orf72 repeat expansions as genetic modifiers for depression in spinocerebellar
      ataxias.

PMID- 29193336
TI  - High Spin Ground States in Matryoshka Actinide Nanoclusters: A Computational
      Study.
AB  - Inspired by the experimentally synthesized Na12 @[(UO2 )(O2 )1.5 ]208- ("Na12
      @U20 ") cluster, we have explored computationally the substitution of the Na
      cations by many other metals. 6 other M12 @U20 systems are found to be stable
      (M=K+ , Rb+ , Cs+ , Ag+ , Mg2+ , Fe2+ ). For 3 of these (Mg2+ , Ag+ and Na+ ),
      the cluster can support a group 16 dianion at its center, forming a new type of
      Matryoshka ("Russian Doll") actinide nanocluster E@M12 @U20 (E=S2- , Se2- , Te2-
      , and Po2- ). These systems have 3-shell, onion-like geometries with nearly
      perfect Ih symmetry. Seeking to create clusters with very high spin ground
      states, we have replaced M by Mn2+ and U20 by Np20 and Pu20 , generating clusters
      with maximum possible S values of 80/2 and 100/2 respectively. Only in the
      presence of a central S2- , however, are these electronic configurations the most
      stable; the novel Matryoshka Pu nanocluster S@Mn12 @Pu20 is predicted to have the
      highest ground state spin yet reported for a molecular cluster.

PMID- 29193337
TI  - The novel echo-guided ProGlide technique during percutaneous transfemoral
      transcatheter aortic valve implantation.
AB  - OBJECTIVES: The aim of this study was to assess clinical benefit of the Echo
      guided ProGlide technique in patients undergoing percutaneous transfemoral
      transcatheter aortic valve implantation (TF-TAVI). BACKGROUND: The efficacy of
      the Echo-guided ProGlide technique during percutaneous TF-TAVI was not previously
      clarified. METHODS: A total of 121 consecutive patients who underwent
      percutaneous TF-TAVI at our institution between February 2014 and July 2017 were
      enrolled in this study. According to the introduction of this novel technique in
      March 2016, patients were divided into two groups (echo-guided group who
      underwent TAVI from March 2016 to July 2017, n = 63; not echo-guided group who
      underwent TAVI from February 2014 to February 2016, n = 58). The incidence of
      major vascular complications, defined per the Valve Academic Research Consortium
      2 criteria, and ProGlide complications including acute femoral artery stenosis or
      occlusion and bleeding requiring any intervention. RESULTS: The incidence of
      major vascular complication and ProGlide complication were significantly lower in
      the echo-guided group than in not echo-guided group (1.6% vs 17.2%, P < 0.002;
      1.6% vs 15.5%, P = 0.003; respectively). Use of the Echo-guided ProGlide
      technique was independently associated with prevention of ProGlide complications
      (odds ratio, 0.11; 95% confidential interval, 0.01-0.76; P = 0.03). CONCLUSIONS:
      This novel Echo-guided ProGlide technique was associated with a lower rate of
      major vascular complications, particularly ProGlide complications during
      percutaneous TF-TAVI.

PMID- 29193338
TI  - The association amongst visual, hearing, and dual sensory loss with depression
      and anxiety over 6 years: The Tromso Study.
AB  - OBJECTIVE: To examine the longitudinal association of dual and single (vision and
      hearing) sensory loss on symptoms of depression and anxiety in older adults.
      METHODS: Two thousand eight hundred ninety adults aged 60 years or over who
      participated in the longitudinal population-based Tromso Study, Norway, were
      included. The impact of objective vision loss, self-report hearing loss, or dual
      sensory loss on symptoms of depression and anxiety, as assessed by the Hopkins
      Symptom Checklist 10, was examined at baseline and 6-year follow-up using linear
      mixed models. RESULTS: Hearing loss had a cross-sectional relationship with
      increased depression (b = 0.1750, SE = 0.07, P = .02) and anxiety symptoms (b =
      0.1765, SE = 0.08, P = .03); however, these relationships were not significant at
      the 6-year follow-up. Both vision loss only and dual sensory loss predicted
      increased depression scores at follow-up (b = 0.0220, SE = 0.01, P = .03; and b =
      0.0413, SE = 0.02, P = .01, respectively). Adjustment for social isolation did
      not attenuate the main depression results. CONCLUSION: Dual sensory loss resulted
      in increased depression symptomatology over time and posed an additional long
      term risk to depression severity beyond having a single sensory loss only. Only
      hearing loss is associated with anxiety symptoms. Older adults with vision,
      hearing, and dual sensory loss have different mental health profiles. Therefore,
      management and intervention should be tailored to the type of sensory loss.

PMID- 29193339
TI  - A rapid T1 mapping method for assessment of murine kidney viability using dynamic
      manganese-enhanced magnetic resonance imaging.
AB  - PURPOSE: Dynamic manganese-enhanced MRI (MEMRI) allows assessment of tissue
      viability by tracing manganese uptake. We aimed to develop a rapid T1 mapping
      method for dynamic MEMRI to facilitate assessments of murine kidney viability.
      METHODS: A multi-slice saturation recovery fast spin echo (MSRFSE) was developed,
      validated, and subsequently applied in dynamic MEMRI at 16.4T on ischemic mouse
      kidneys after 4 weeks of unilateral renal artery stenosis (RAS). Baseline T1
      values and post-contrast R1 (1/T1 ) changes were measured in cortex (CO), outer
      (OSOM), inner (ISOM) strips of outer medulla, and inner medulla (IM). RESULTS:
      Validation studies showed strong agreement between MSRFSE and an established
      saturation recovery Look-Locker method. Baseline T1 (s) increased in the stenotic
      kidney CO (2.10 [1.95-2.56] vs. 1.88 [1.81-2.00], P = 0.0317) and OSOM (2.17
      [2.05-2.33] vs. 1.96 [1.87-2.00], P = 0.0075) but remained unchanged in ISOM and
      IM. This method allowed a temporal resolution of 1.43 min in dynamic MEMRI. Mn2+
      uptake and retention decreased in stenotic kidneys, particularly in the OSOM
      (DeltaR1 : 0.48 [0.38-0.56] vs. 0.64 [0.61-0.69] s-1 , P < 0.0001). CONCLUSION:
      Dynamic MEMRI by MSRFSE detected decreased cellular viability and discerned the
      regional responses to RAS. This technique may provide a valuable tool for
      noninvasive evaluation of renal viability. Magn Reson Med 80:190-199, 2018. (c)
      2017 International Society for Magnetic Resonance in Medicine.

PMID- 29193340
TI  - Template-based field map prediction for rapid whole brain B0 shimming.
AB  - PURPOSE: In typical MRI protocols, time is spent acquiring a field map to
      calculate the shim settings for best image quality. We propose a fast template
      based field map prediction method that yields near-optimal shims without
      measuring the field. METHODS: The template-based prediction method uses prior
      knowledge of the B0 distribution in the human brain, based on a large database of
      field maps acquired from different subjects, together with subject-specific
      structural information from a quick localizer scan. The shimming performance of
      using the template-based prediction is evaluated in comparison to a range of
      potential fast shimming methods. RESULTS: Static B0 shimming based on predicted
      field maps performed almost as well as shimming based on individually measured
      field maps. In experimental evaluations at 7 T, the proposed approach yielded a
      residual field standard deviation in the brain of on average 59 Hz, compared with
      50 Hz using measured field maps and 176 Hz using no subject-specific shim.
      CONCLUSIONS: This work demonstrates that shimming based on predicted field maps
      is feasible. The field map prediction accuracy could potentially be further
      improved by generating the template from a subset of subjects, based on
      parameters such as head rotation and body mass index. Magn Reson Med 80:171-180,
      2018. (c) 2017 The Authors Magnetic Resonance in Medicine published by Wiley
      Periodicals, Inc. on behalf of International Society for Magnetic Resonance in
      Medicine. This is an open access article under the terms of the Creative Commons
      Attribution License, which permits use, distribution and reproduction in any
      medium, provided the original work is properly cited.

PMID- 29193341
TI  - Functional Disilenes in Synthesis.
AB  - Functionalized disilenes are valuable auxiliary tools in preparative chemistry.
      In the following review the various synthetic potential of disilenes as
      precursors is presented. Upon consumption of the Si=Si unit in disilenes, cyclic,
      polycyclic and cluster-like arrangements are obtainable.

PMID- 29193342
TI  - Miscellaneous.

PMID- 29193343
TI  - Response to considerations on "Achilles tendinopathy and patellar tendinopathy
      display opposite changes in elastic properties".

PMID- 29193345
TI  - Multidisciplinary Efforts Advance Materials Research at Beihang University.

PMID- 29193344
TI  - epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h
      Peptide to Induce Apoptosis in Cancer Cells.
AB  - Apoptotic signaling pathways are altered in numerous pathologies such as cancer.
      In this scenario, caspase-9/PP2Acalpha interaction constitutes a key target with
      pharmacological interest to re-establish apoptosis in tumor cells. Very recently,
      a short peptide (C9h) known to disrupt caspase-9/PP2Acalpha interaction with
      subsequent apoptosis induction was described. Here, we prepared two sets of
      mesoporous silica nanoparticles loaded with safranin O (S2) or with C9h peptide
      (S4) and functionalized with epsilon-polylysine as capping unit. Aqueous
      suspensions of both nanoparticles showed negligible cargo release whereas in the
      presence of pronase, a marked delivery of safranin O or C9h was observed.
      Confocal microscopy studies carried out with HeLa cells indicated that both
      materials were internalized and were able to release their entrapped cargos.
      Besides, a marked decrease in HeLa cell viability (ca. 50 %) was observed when
      treated with C9h-loaded S4 nanoparticles. Moreover, S4 provides peptide
      protection from degradation additionally allowing for a dose reduction to observe
      an apoptotic effect when compared with C9h alone or in combination with a cell
      penetrating peptide (i.e., Mut3DPT-C9h). Flow cytometry studies, by means of
      Annexin V-FITC staining, showed the activation of apoptotic pathways in HeLa as a
      consequence of S4 internalization, release of C9h peptide and disruption of
      caspase-9/PP2Acalpha interaction.

PMID- 29193346
TI  - Biomimetic Platelet-Camouflaged Nanorobots for Binding and Isolation of
      Biological Threats.
AB  - One emerging and exciting topic in robotics research is the design of micro
      /nanoscale robots for biomedical operations. Unlike industrial robots that are
      developed primarily to automate routine and dangerous tasks, biomedical
      nanorobots are designed for complex, physiologically relevant environments, and
      tasks that involve unanticipated biological events. Here, a biologically
      interfaced nanorobot is reported, made of magnetic helical nanomotors cloaked
      with the plasma membrane of human platelets. The resulting biomimetic nanorobots
      possess a biological membrane coating consisting of diverse functional proteins
      associated with human platelets. Compared to uncoated nanomotors which experience
      severe biofouling effects and hence hindered propulsion in whole blood, the
      platelet-membrane-cloaked nanomotors disguise as human platelets and display
      efficient propulsion in blood over long time periods. The biointerfaced
      nanorobots display platelet-mimicking properties, including adhesion and binding
      to toxins and platelet-adhering pathogens, such as Shiga toxin and Staphylococcus
      aureus bacteria. The locomotion capacity and platelet-mimicking biological
      function of the biomimetic nanomotors offer efficient binding and isolation of
      these biological threats. The dynamic biointerfacing platform enabled by platelet
      membrane cloaked nanorobots thus holds considerable promise for diverse
      biomedical and biodefense applications.

PMID- 29193347
TI  - In Memoriam Ben Vainer 18.6.1969-21.6.2017.

PMID- 29193348
TI  - Heading for centennial anniversary and beyond.

PMID- 29193349
TI  - Tunability of Open-Shell Character, Charge Asymmetry, and Third-Order Nonlinear
      Optical Properties of Covalently Linked (Hetero)Phenalenyl Dimers.
AB  - Tunability of the open-shell character, charge asymmetry, and third-order
      nonlinear optical (NLO) properties of covalently linked (hetero)phenalenyl dimers
      are investigated by using the density functional theory method. By changing the
      molecular species X and substitution position (i, j) for the linker part, a
      variety of intermonomer distances R and relative alignments between the
      phenalenyl dimers can be realized from the geometry optimizations, resulting in a
      wide-range tuning of diradical character y and charge asymmetry. It is found that
      the static second hyperpolarizabilities along the stacking direction, gammayyyy ,
      are one-order enhanced for phenalenyl dimer systems exhibiting intermediate y, a
      feature that is in good agreement with the "y-gamma correlation". By replacing
      the central carbon atoms of the phenalenyl rings with a boron or a nitrogen, we
      have also designed covalently linked heterophenalenyl dimers. The introduction of
      such a charge asymmetry to the open-shell systems, which leads to closed-shell
      ionic ground states, is found to further enhance the gammayyyy values of the
      systems having longer intermonomer distance R with intermediate ionic character,
      that is, charge asymmetry. The present results demonstrate a promising potential
      of covalently linked NLO dimers with intermediate open-shell/ionic characters as
      a new building block of highly efficient NLO systems.

PMID- 29193350
TI  - Curcumin nanomicelle improves semen parameters, oxidative stress, inflammatory
      biomarkers, and reproductive hormones in infertile men: A randomized clinical
      trial.
AB  - At least 50% of infertile couple's problems are related to male factor
      infertility. This Randomized, Double-Blind, Placebo-Controlled Clinical Trial
      conducted in Urology unit of Infertility Clinic on 60 infertile men. Patients
      were randomly assigned to one of intervention and placebo (n = 30) groups.
      Finally, 28 subjects in each group completed the study. Participants in the
      intervention group took daily 80 mg curcumin nanomicelle and those in the placebo
      group took daily placebo for 10 weeks. Semen analysis, anthropometric, physical
      activity assessments, total antioxidant capacity, malondialdehyde, inflammatory
      factors, and reproductive hormones were measured at the baseline and at the end
      of the study. At the end of study, statistically significant differences were
      seen in the total sperm count, sperm concentration, and motility in the
      intervention group to the control group. In treatment group, the total sperm
      count, sperm concentration, and motility levels were also statistically increased
      at the end of study compared to the baseline values. Curcumin nanomicelle
      supplementation also resulted in a statistically significant improvement in
      plasma levels of total antioxidant capacity, malondialdehyde, C-reactive protein,
      and tumor necrosis factor a in comparison to the placebo. Medical therapy of
      asthenoteratospermia with curcumin nanomicelle supplement could improve quality
      of semen parameters. However, further investigation is suggested in this regard.

PMID- 29193351
TI  - The Scandinavian Foundation of Medicine & Science in Sports.

PMID- 29193352
TI  - Effectiveness of fenugreek as a galactagogue: A network meta-analysis.
AB  - A systematic review and network-meta analysis (NMA) were performed to test
      significance of the galactagogue effect of fenugreek administrated to lactating
      women versus other comparators (i.e., placebo/control/other galactagogues). A
      pairwise comparison for the treatment effect was carried out to generate the
      forest plot for the NMA. League tables were generated using treatment effect,
      weighted mean difference (WMD; 95% confidence interval, CI) for all pairwise
      comparisons, where WMD > 0 favors the column-defining treatment. Five studies
      were identified with 122 participants receiving treatment with fenugreek. The NMA
      results of 4 studies indicated that consumption of fenugreek significantly
      increased amount of the produced breast milk [11.11, CI 95% 6.77, 15.46] versus
      placebo. The pairwise comparison revealed that fenugreek was effective as a
      galactagogue compared to placebo, control, and reference groups WMD 17.79 [CI
      11.71, 23.88]. However, the effect of fenugreek was substantially inferior to
      Coleus amboinicus Lour and palm date. The NMA using pairwise comparison
      demonstrated the effect of C. amboinicus and palm date in the stimulation of the
      breast milk production was comparable and superior to all comparators.

PMID- 29193353
TI  - Gingival crevicular fluid and its immune mediators in the proteomic era.
AB  - The discovery of biomarkers for periodontal disease requires an in-depth
      understanding of the molecular basis of the initiation and progression of the
      disease. The gingival crevicular fluid is a biological medium suitable for
      identifying and measuring such biomarkers because it can be easily and
      noninvasively sampled from the immediate vicinity of the affected tissues. An
      ever-expanding pool of gingival crevicular fluid proteins associated with
      periodontal health or disease has been catalogued over the years, particularly
      with the recent implementation of proteomic technologies. 'Proteomics' refers to
      the large-scale study of entire arrays of proteins expressed by a genome and
      present in a cell, tissue, biological fluid or organism. Hence, such technologies
      provide a broad qualitative and quantitative insight of the proteins present in
      gingival crevicular fluid. Pertinent studies have amassed on the information
      gathered to date on protein signatures in periodontal health and disease, and
      have confirmed the nature of the immunological host response. This review
      discusses the application of proteomic technologies in characterizing the
      molecular networks present in gingival crevicular fluid, their potential for
      discovery of biomarkers that are meaningful for clinical practice, and the
      associated technical challenges.

PMID- 29193354
TI  - Decursin attenuates the amyloid-beta-induced inflammatory response in PC12 cells
      via MAPK and nuclear factor-kappaB pathway.
AB  - Decursin, the major bioactive component of Angelica gigas Nakai, exhibited
      neuroprotective properties. Our previous studies showed that decursin conferred
      neuroprotective effects in PC12 cells induced by Amyloid-beta (Abeta)25-35 via
      antiapoptosis and antioxidant. In this study, the antiinflammatory effects of
      decursin against PC12 cells injury stimulated by Abeta25-35 were assessed. Our
      results demonstrated that decursin suppressed the expression of cyclooxygenase-2
      protein and prostaglandin E2 content which was stimulated by Abeta25-35 in PC12
      cells. Meanwhile, the nuclear translocation of nuclear factor-kappaB in Abeta25
      35 -treated PC12 cells was also inhibited by decursin. In addition, decursin
      suppressed phosphorylation of the two upstream pathway kinases, p38 and c-Jun N
      terminal kinase. Overall, our findings indicate that decursin exerts protective
      effects against neuroinflammation stimulated by Abeta25-35 in PC12 cells by
      abolishing cyclooxygenase-2 protein expression through inactivation of nuclear
      factor-kappaB via the upstream kinases including p38 and c-Jun N-terminal kinase.
      This work provides a new insight into the pharmacological mode of decursin and
      should facilitate its therapeutic application in treatment of inflammatory
      disorders.

PMID- 29193355
TI  - Development of the gingival sulcus at the time of tooth eruption and the
      influence of genetic factors.
AB  - Tooth eruption is characterized by a concert of mechanisms that result in the
      emergence of teeth in the oral cavity. Genetic variants seem to regulate this
      process and the formation of a gingival sulcus around the teeth. Interindividual
      variability in the response to microbial triggers in the sulcus plays an
      important role in the onset and progression of periodontal diseases. Host genetic
      variants can influence this variability, affecting the response of the host to
      the subgingival biofilm. Genetic factors affecting tooth eruption could
      potentially influence susceptibility to periodontal diseases and, specifically,
      susceptibility to localized aggressive periodontitis. This review aims to discuss
      the evidence available for the role of host genetic variants in tooth eruption
      and to and to give some directions for prospective research in this topic.

PMID- 29193356
TI  - Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for
      post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A
      prospective study.
AB  - BACKGROUND: In 2012, an Italian Named Patient Program began for hepatitis C virus
      (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before
      approval of direct antiviral agents (DAA), to benefit severely ill patients. The
      aim of this "real-life" study was to assess treatment efficacy and safety with an
      extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without
      ribavirin (RBV). METHODS: All HCV LT recipients with severe fibrosis in 15
      Italian transplant centers were treated with DCV+SOF+/-RBV for 24 weeks;
      sustained virological response was assessed at 12 weeks post-treatment (SVR12).
      RESULTS: Eighty-seven patients were enrolled (75.9% males, mean age 58.4 +/- 7.2
      years, 83.9% genotype 1, 81.6% cirrhosis); 52 (59.8%) received RBV. Overall, 79
      obtained SVR12 (90.8%): 100% in F3 and 88.7% in cirrhotics (91.5% in Child-Pugh
      A, 83.3% in Child-Pugh B and C). According to the treatment group, SVR was 80% in
      DCV + SOF group and 98.1% in SOF + DCV + RBV. Two virological relapses occurred
      during follow-up in cirrhotic patients who received DCV + SOF. Four cirrhotic
      patients in DCV + SOF group and 1 in DCV + SOF + RBV group died on treatment.
      CONCLUSION: An extended course of SOF plus DCV for 24 weeks, with or without RBV,
      is effective and well tolerated for the treatment of post-LT HCV recurrence with
      severe fibrosis.

PMID- 29193357
TI  - What phytotherapy needs: Evidence-based guidelines for better clinical practice.
AB  - In recent decades, the pharmacological properties of numerous medicinal plants
      and opportunities in phytotherapy have been explored through research projects,
      reviews, and monographs. These studies confirm that medicinal plants offer new
      approaches to tackling diseases. However, improvement of phytotherapy in clinical
      practice relies on a number of critical factors. In particular, the studies are
      very heterogeneous, and results and their interpretation by healthcare workers
      vary greatly, so preventing consistency in clinical practice. There is therefore
      a lost opportunity to improve phytotherapy practice, because the work being done
      and the related systematic reviews cannot act as a body of data on which to base
      clear clinical recommendations. Approaches such as the Grading of Recommendations
      Assessment, Development and Evaluation or the Scottish Intercollegiate Guidelines
      Network methodology could easily help standardise the use of phytotherapy in
      clinical practice. In this context, evidence-based phytotherapy guidelines could
      offer new healthcare approaches to the treatment of diseases.

PMID- 29193359
TI  - Consensus Statement on the classification of tremors. from the task force on
      tremor of the International Parkinson and Movement Disorder Society.
AB  - BACKGROUND: Consensus criteria for classifying tremor disorders were published by
      the International Parkinson and Movement Disorder Society in 1998. Subsequent
      advances with regard to essential tremor, tremor associated with dystonia, and
      other monosymptomatic and indeterminate tremors make a significant revision
      necessary. OBJECTIVES: Convene an international panel of experienced
      investigators to review the definition and classification of tremor. METHODS:
      Computerized MEDLINE searches in January 2013 and 2015 were conducted using a
      combination of text words and MeSH terms: "tremor", "tremor disorders",
      "essential tremor", "dystonic tremor", and "classification" limited to human
      studies. Agreement was obtained using consensus development methodology during
      four in-person meetings, two teleconferences, and numerous manuscript reviews.
      RESULTS: Tremor is defined as an involuntary, rhythmic, oscillatory movement of a
      body part and is classified along two axes: Axis 1-clinical characteristics,
      including historical features (age at onset, family history, and temporal
      evolution), tremor characteristics (body distribution, activation condition),
      associated signs (systemic, neurological), and laboratory tests
      (electrophysiology, imaging); and Axis 2-etiology (acquired, genetic, or
      idiopathic). Tremor syndromes, consisting of either isolated tremor or tremor
      combined with other clinical features, are defined within Axis 1. This
      classification scheme retains the currently accepted tremor syndromes, including
      essential tremor, and provides a framework for defining new syndromes.
      CONCLUSIONS: This approach should be particularly useful in elucidating isolated
      tremor syndromes and syndromes consisting of tremor and other signs of uncertain
      significance. Consistently defined Axis 1 syndromes are needed to facilitate the
      elucidation of specific etiologies in Axis 2. (c) 2017 International Parkinson
      and Movement Disorder Society.

PMID- 29193358
TI  - Cardiovascular magnetic resonance elastography: A review.
AB  - Cardiovascular diseases are the leading cause of death worldwide. These
      cardiovascular diseases are associated with mechanical changes in the myocardium
      and aorta. It is known that stiffness is altered in many diseases, including the
      spectrum of ischemia, diastolic dysfunction, hypertension and hypertrophic
      cardiomyopathy. In addition, the stiffness of the aortic wall is altered in
      multiple diseases, including hypertension, coronary artery disease and aortic
      aneurysm formation. For example, in diastolic dysfunction in which the ejection
      fraction is preserved, stiffness can potentially be an important biomarker.
      Similarly, in aortic aneurysms, stiffness can provide valuable information with
      regard to rupture potential. A number of studies have addressed invasive and non
      invasive approaches to test and measure the mechanical properties of the
      myocardium and aorta. One of the non-invasive approaches is magnetic resonance
      elastography (MRE). MRE is a phase-contrast magnetic resonance imaging technique
      that measures tissue stiffness non-invasively. This review article highlights the
      technical details and application of MRE in the quantification of myocardial and
      aortic stiffness in different disease states.

PMID- 29193361
TI  - Automatic analysis of corneal nerves imaged using in vivo confocal microscopy.
AB  - Interest has grown over the past decade in using in vivo confocal microscopy to
      analyse the morphology of corneal nerves and their changes over time. Advances in
      computational modelling techniques have been applied to automate the estimation
      of sub-basal nerve structure. These objective methods have the potential to
      quantify nerve density (and length), tortuosity, variations in nerve thickness,
      as well as temporal changes in nerve fibres such as migration patterns. Different
      approaches to automated nerve analysis, methods proposed and how they were
      validated in previous literature are reviewed. Improved understanding of these
      approaches and their limitations will help improve the diagnostic leverage of
      emerging developments for monitoring the onset and progression of a broad class
      of systemic diseases, including diabetes.

PMID- 29193360
TI  - Patterns of late-life depressive symptoms and subsequent declines in cognitive
      domains.
AB  - BACKGROUND: Depression frequently co-occurs with cognitive decline, but the
      nature of this association is unclear. We examined relations of late-life
      depressive symptom patterns to subsequent domain-specific cognitive changes.
      METHODS: Depressive symptoms were measured at up to 3 timepoints among 11,675
      Nurses' Health Study participants prior to cognitive testing. Depressive symptom
      patterns were categorized as non-depressed, variable or persistent, based on
      published severity cutpoints. Outcomes were global, verbal, and executive
      function-attention composite scores. RESULTS: Participants with persistent
      depressive symptoms had worse executive function-attention decline compared with
      non-depressed participants (multivariable-adjusted mean difference = -0.03
      units/year, 95% CI: -0.05, -0.01; p = 0.003); this difference was comparable with
      8 years of aging. However, being in the persistent versus non-depressed group was
      not significantly related to verbal (p = 0.71) or global score (p = 0.09)
      decline. By contrast, compared with the non-depressed group, those with variable
      depressive symptoms had worse verbal memory decline (multivariable-adjusted mean
      difference = -0.01 units/year, 95% CI: -0.02, -0.002; p = 0.03); this group
      showed no differences for global or executive function-attention decline.
      CONCLUSIONS: A variable pattern of depressive symptom severity related to
      subsequent decline in verbal memory, while a persistent pattern related to
      decline in executive function-attention. Findings could signal differences in
      underlying neuropathologic processes among persons with differing depression
      patterns and late-life cognitive decline. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 29193362
TI  - Donor-specific anti-HLA antibodies are not associated with nonanastomotic biliary
      strictures but both are independent risk factors for graft loss after liver
      transplantation.
AB  - Donor-specific alloantibodies (DSA) have been associated with rejection and
      shorter graft survival after orthotopic liver transplantation (OLT). We examined
      the role of DSA in nonanastomotic biliary strictures (NAS) after OLT. Patients
      receiving first OLT who developed NAS (n = 68) and a control group without NAS (n
      = 83), with pre-OLT and 12 months post-OLT serum samples, were included. DSA were
      specified using the Luminex single antigen test. Risk factors for NAS and graft
      survival were analyzed. The presence of preformed DSA was not significantly
      different between patients with NAS and controls (P = .89). After 12 months,
      26.5% of NAS patients and 16.9% of controls had generated de novo DSA (P = .15).
      Neither de novo class I DSA nor de novo class II DSA were associated with NAS. De
      novo DSA generally developed after the diagnosis of NAS. Time-dependent
      regression analysis identified both NAS (aHR 8.05, CI 3.28 - 19.77, P < .01) and
      de novo class II DSA (aHR 2.84, CI 1.38 - 5.82, P < .01) as independent risk
      factors for graft loss. Preformed or de novo DSA were not associated with the
      development of NAS. However, NAS as well as de novo class II DSA were independent
      risk factors for graft loss after OLT.

PMID- 29193363
TI  - Anti-MRSA activity of oxysporone and xylitol from the endophytic fungus
      Pestalotia sp. growing on the Sundarbans mangrove plant Heritiera fomes.
AB  - Heritiera fomes Buch.-Ham., a mangrove plant from the Sundarbans, has adapted to
      a unique habitat, muddy saline water, anaerobic soil, brackish tidal activities,
      and high microbial competition. Endophytic fungal association protects this plant
      from adverse environmental conditions. This plant is used in Bangladeshi folk
      medicine, but it has not been extensively studied phytochemically, and there is
      hardly any report on investigation on endophytic fungi growing on this plant. In
      this study, endophytic fungi were isolated from the surface sterilized cladodes
      and leaves of H. fomes. The antimicrobial activities were evaluated against two
      Gram-positive and two Gram-negative bacteria and the fungal strain, Candida
      albicans. Extracts of Pestalotia sp. showed activities against all test bacterial
      strains, except that the ethyl acetate extract was inactive against Escherichia
      coli. The structures of the purified compounds, oxysporone and xylitol, were
      elucidated by spectroscopic means. The anti-MRSA potential of the isolated
      compounds were determined against various MRSA strains, that is, ATCC 25923, SA
      1199B, RN4220, XU212, EMRSA-15, and EMRSA-16, with minimum inhibitory
      concentration values ranging from 32 to 128 MUg/ml. This paper, for the first
      time, reports on the anti-MRSA property of oxysporone and xylitol, isolation of
      the endophyte Pestalotia sp. from H. fomes, and isolation of xylitol from a
      Pestalotia sp.

PMID- 29193364
TI  - The influence and mechanism of ligustilide, senkyunolide I, and senkyunolide A on
      echinacoside transport through MDCK-MDR1 cells as blood-brain barrier in vitro
      model.
AB  - Efficient transcytosis across the blood-brain-barrier is an important strategy
      for accessing drug targets within the central nervous system. Ligusticum
      chuanxiong Hort. was used as a messenger drug to increase the distribution of
      drugs in brain tissue in Traditional Chinese Medicine. The present study
      investigates the transport of echinacoside (ECH) through MDCK-MDR1 cell and the
      effects of ligustilide (LIG), senkyunolide A (SENA) and senkyunolide I (SENI) in
      chuanxiong on its transport. The results indicated that the absorption of ECH was
      relatively poor in MDCK-MDR1cells, and was concentration dependent and not
      saturable. The P-glycoprotein inhibitor verapamil could significantly increase
      the transport of ECH. It indicated that the transport mechanism might be passive
      diffusion as the dominating process with the active transportation mediated
      mechanism involved. The increased apparent permeability of ECH in A -> B
      direction by ethylenediaminetetraacetic acid-Na2 suggested that ECH was absorbed
      via the paracellular route. The transport of ECH in A -> B direction
      significantly increased when co-administrated with increasing concentrations of
      LIG, SENI and SENA. Western blot analysis and a decrease in transepithelial
      electrical resistance during the permeation experiment indicated that LIG, SENI
      and SENA had enhanced the transport of ECH in the BBB models attribute to down
      regulate the expressions of claudin-5 and zonula occludens-1 expression.

PMID- 29193365
TI  - Making the leap to medical education: a qualitative study of medical educators'
      experiences.
AB  - CONTEXT: Medical educators often have prior and primary experience in other
      academic and clinical disciplines. Individuals seeking successful careers in the
      education of medical students and doctors must, at some point in their
      development, make a conscious transition into a new identity as a medical
      educator. This is a necessary move if individuals are to commit to acquiring and
      maintaining specialist expertise in medical education. Some achieve this
      transition successfully, whereas others struggle and may even lose interest and
      abandon the endeavour. We explored senior educators' experiences of achieving the
      transition into medical education and their views on what helps and what hinders
      the process. METHODS: In 2015 we conducted three focus groups with 15 senior
      medical educators. All focus group discussions were audiorecorded and transcribed
      verbatim. We applied transition theory to guide our deductive analysis, using
      Schlossberg's Four S (4S) framework to code and report participants' self
      reported perceptions of those factors relating to Self, Situation, Support and
      Strategy that had assisted them to make a successful transition to a fully
      acknowledged medical educator identity. Through inductive analysis, we then
      identified 17 explanatory sub-themes common to all three focus groups. RESULTS:
      Background and circumstances, individual motivation, a sense of control,
      organisational support, and effective networking and information-seeking
      behaviour were factors identified as contributing to successful transition into,
      and maintenance of, a strong self-identity as a medical educator. CONCLUSIONS:
      The experiences of established medical educators and, in particular, an
      exploration of the factors that have facilitated their transition to an
      acknowledged self-identity as a medical educator could assist in supporting new
      educators to cope with the changes involved in developing as a medical educator.

PMID- 29193366
TI  - Self-Assembled alpha-Cyanostilbenes for Advanced Functional Materials.
AB  - In the specific context of condensed media, the significant and increasing recent
      interest in the alpha-cyanostilbene (CS) motif [?Ar?CH?C(CN)?Ar?] is relevant.
      These compounds have shown remarkable optical features in addition to interesting
      electrical properties, and hence they are recognized as very suitable and
      versatile options for the development of functional materials. This progress
      report is focused on current and future use of CS structures and molecular
      assemblies with the aim of exploring and developing for the next generations of
      functional materials. A critical selection of illustrative materials that contain
      the CS motif, including relevant subfamilies such as the dicyanodistyrylbenzene
      and 2,3,3-triphenylacrylonitrile shows how, driven by the self-assembly of CS
      blocks, a variety of properties, effects, and possibilities for practical
      applications can be offered to the scientific community, through different
      rational routes for the elaboration of advanced materials. A survey is provided
      on the research efforts directed toward promoting the self-assembly of the solid
      state (polycrystalline solids, thin films, and single crystals), liquid crystals,
      nanostructures, and gels with multistimuli responsiveness, and applications for
      sensors, organic light-emitting diodes, organic field effect transistors, organic
      lasers, solar cells, or bioimaging purposes.

PMID- 29193367
TI  - Cytotoxic activity of carotenoid rich fractions from Haematococcus pluvialis and
      Dunaliella salina microalgae and the identification of the phytoconstituents
      using LC-DAD/ESI-MS.
AB  - Microalgae represent a rich source that satisfies the growing need for novel
      ingredients of nutriceuticals, pharmaceuticals, and food supplements.
      Haematococcus pluvialis and Dunaliella salina microalgae are isolated from the
      Egyptian hydro-flora and are reported for their potent antioxidant activities.
      The cytotoxic activity of different fractions of both microalgae was investigated
      on 4 cell lines HePG2, MCF7, HCT116, and A549. The carotenoid rich fraction of H.
      pluvialis showed potent cytotoxic activity against colon cancer cell line and
      moderate activity against both liver and breast cancer cell lines. On the other
      hand, the carotenoid rich fraction of D. salina showed mild cytotoxic activity on
      breast and liver cancer cell lines. The carotenoid rich fraction of H. pluvialis
      was analysed using LC-DAD/ESI-MS and the major carotenoids were identified either
      free as well as bounded to fatty acids.

PMID- 29193368
TI  - Curcumin, an antibiotic resistance breaker against a multiresistant clinical
      isolate of Mycobacterium abscessus.
AB  - Curcumin, a phenolic compound extracted from Curcuma longa, exerts multiple
      pharmacological effects, including an antimicrobial action. Mycobacterium
      abscessus, an environmental, nontuberculous, rapidly growing mycobacterium, is an
      emerging human pathogen causing serious lung infections and one of the most
      difficult to treat, due to its multidrug resistance and biofilm-forming ability.
      We wanted to evaluate the antimicrobial and antivirulence activity of curcumin
      and its ability to synergize with antibiotics against a clinical M. abscessus
      strain (29904), isolated from the bronchoaspirate of a 66-year-old woman admitted
      to hospital for suspected tuberculosis. Curcumin [minimum inhibitory
      concentrations (MIC) = 128 mg/L] was synergic (fractional inhibitory
      concentration index <=0.5) with amikacin, clarithromycin, ciprofloxacin, and
      linezolid, to which strain 29904 showed resistance/intermediate susceptibility.
      Curcumin at 1/8 * MIC significantly reduced motility, whereas at 4 * MIC, it
      completely inhibited 4- and 8-day mature biofilms. Synergistic combinations of
      curcumin and amikacin induced a general reduction in microbial aggregates and
      substantial loss in cell viability. Disruption of 4- and 8-day biofilms was the
      main effect detected when curcumin was the predominant compound. The present
      findings support previous evidence that curcumin is a potential antibiotic
      resistance breaker. Curcumin, either alone or combined with antibiotics, could
      provide a novel strategy to combat antibiotic resistance and virulence of M.
      abscessus.

PMID- 29193369
TI  - Soft Chemistry, Coloring and Polytypism in Filled Tetrahedral Semiconductors:
      Toward Enhanced Thermoelectric and Battery Materials.
AB  - Filled tetrahedral semiconductors are a rich family of compounds with tunable
      electronic structure, making them ideal for applications in thermoelectrics,
      photovoltaics, and battery anodes. Furthermore, these materials crystallize in a
      plethora of related structures that are very close in energy, giving rise to
      polytypism through the manipulation of synthetic parameters. This Minireview
      highlights recent advances in the solution-phase synthesis and nanostructuring of
      these materials. These methods enable the synthesis of metastable phases and
      polytypes that were previously unobtainable. Additionally, samples synthesized in
      solution phase have enhanced thermoelectric performance due to their decreased
      grain size.

PMID- 29193370
TI  - Valence Localization at a Bio-inspired Mixed-Valent {Cu2 S}2+ Motif upon
      Solvation in Acetonitrile: Effect on Nitrous Oxide Reductase (N2 Or) Activity.
AB  - We demonstrate, based on experimental and theoretical evidence, that the isolated
      [2(CH3 CN)2 ]2+ complex prepared in CH3 CN and containing a mixed-valent {Cu2II,I
      S} core evolves towards a new [2(CH3 CN)3 ]2+ species upon solvation in CH3 CN.
      Unlike its type III structural analogue [2(H2 O)(OTf)]+ active toward N2 O
      reduction, this new type I compound is inactive. This outcome opens new
      perspectives for a rational for N2 O activation using bio-inspired Cu/S
      complexes, especially on the role of the valence localization/delocalization and
      the Cu-Cu bond on the reactivity.

PMID- 29193372
TI  - Summary of the UAA-AAUS guidelines for urinary tract infections.
AB  - Urinary tract infections, genital tract infections and sexually transmitted
      infections are the most prevalent infectious diseases, and the establishment of
      locally optimized guidelines is critical to provide appropriate treatment. The
      Urological Association of Asia has planned to develop the Asian guidelines for
      all urological fields, and the present urinary tract infections, genital tract
      infections and sexually transmitted infections guideline was the second project
      of the Urological Association of Asia guideline development, which was carried
      out by the Asian Association of Urinary Tract Infection and Sexually Transmitted
      Infection. The members have meticulously reviewed relevant references, retrieved
      via the PubMed and MEDLINE databases, published between 2009 through 2015. The
      information identified through the literature review of other resources was
      supplemented by the author. Levels of evidence and grades of recommendation for
      each management were made according to the relevant strategy. If the judgment was
      made on the basis of insufficient or inadequate evidence, the grade of
      recommendation was determined on the basis of committee discussions and resultant
      consensus statements. Here, we present a short English version of the original
      guideline, and overview its key clinical issues.

PMID- 29193371
TI  - Differential interaction of PRMT1 with RGG-boxes of the FET family proteins EWS
      and TAF15.
AB  - The FET sub-family (FUS/TLS, EWS, TAF15) of RNA-binding proteins have remarkably
      similar overall structure but diverse biological and pathological roles. The
      molecular basis for FET protein specialization is largely unknown. Gly-Arg-Rich
      regions (RGG-boxes) within FET proteins are targets for methylation by Protein
      Arginine-Methyl-Transferase-1 (PRMT1) and substrate capture is thought to involve
      electrostatic attraction between positively charged polyRGG substrates and
      negatively charged surface channels of PRMT1. Unlike FUS and EWS, a high
      proportion of TAF15 RGG-boxes are embedded within neutrally charged YGGDR(S/G)G
      repeats, suggesting that they might not bind well to PRMT1. This notion runs
      contrary however to a report that YGGDR(S/G)G repeats are methylated by PRMT1.
      Using peptide-based polyRGG substrates and a novel 2-hybrid binding assay, we
      find that the Asp residue in YGGDR(S/G)G repeats confers poor binding to PRMT1.
      Our results therefore indicate that YGGDR(S/G)G repeats may contribute to TAF15
      specialization by enabling differential interactions with PRMT1 and reduced
      overall levels of TAF15 methylation compared with other FET proteins. By analogy
      with molecular recognition of other disordered polyvalent ligands by globular
      protein partners, we also propose a dynamic polyelectrostatic model for substrate
      capture by PRMT1.

PMID- 29193373
TI  - Solid-State Structure of Tris-Cyclopentadienide Uranium(III) and Plutonium(III).
AB  - The organometallic tris-cyclopentadienide actinide(III) (AnCp3 ) complexes were
      first reported about 50 years ago. However, up until now, only the NpCp3 solid
      state structure has been studied. Here we report on the solid state structures of
      UCp3 and PuCp3 which are isostructural to the Np analogue. The structural models
      are supported by theoretical calculations and compared to their lanthanide
      analogues. The observed trends in changes of bond lengths might be indicator for
      an increased covalency in the bonding in the tris-cyclopentadienide actinide(III)
      complexes (AnCp3 ) compared to their lanthanide homologues.

PMID- 29193374
TI  - Tunable Emission from Fluorescent Organic Nanoparticles in Water: Insight into
      the Nature of Self-Assembly and Photoswitching.
AB  - Excitation-dependent tuning of the emission behavior of fluorescent organic
      nanoparticles (FONs) with two simple luminescent pyrenyl-pyridyl conjugates as
      model systems is demonstrated. In the case of the compound with a flexible bis
      picolyl moiety, the simultaneous presence of multiple ground-state species with
      distinct absorption and emission characteristics can be observed. The relative
      ratios of these species can easily be modulated, and it is possible to
      selectively stimulate any one of them individually by choosing an appropriate
      excitation channel. Moreover, at high concentration, a drastic change in the
      nature of the self-assembly is observed, which shifts from donor-acceptor-type
      self-assembly to exciplex-type self-agglomeration. On the contrary, the compound
      containing a rigid terpyridine unit has only a single ground state and shows no
      such tunable emission. However, it can exhibit multiple emission bands in water,
      whereby the positions of their emission maxima depend on the extent of
      aggregation-induced planarization of the probe molecules. Overall, this work
      demonstrates multimodal modulation of FON emission and a gives insight into how
      molecular order can translate into complete switching of nanoparticle self
      assembly and photophysics.

PMID- 29193375
TI  - National Comparative Audit of Blood Transfusion: report on the 2014 audit of
      patient information and consent.
AB  - OBJECTIVES: The aim of this study was to assess current practices around
      obtaining consent for blood transfusion and provision of patient information in
      hospitals across the UK and identify areas for improvement. BACKGROUND:
      Recommendations from the Advisory Committee on the Safety of Blood, Tissues and
      Organs (SaBTO) (2011) state that valid consent should be obtained for blood
      transfusion and documented in clinical records. A standardised source of
      information should be available to patients. Practices in relation to this have
      historically been inconsistent. METHODS: The consent process was studied in
      hospitals across the UK over a 3-month period in 2014 by means of an audit of
      case notes and simultaneous surveys of patients and staff. RESULTS: In total,
      2784 transfusion episodes were reviewed across 164 hospital sites. 85% of sites
      had a policy on consent for transfusion. Consent was documented in 43% of case
      notes. 68% of patients recalled being given information on benefits of
      transfusion, 38% on risks and 8% on alternatives and 28% reported receiving an
      information leaflet. In total, 85% of staff stated they had explained the reason
      for transfusion, but only 65% had documented this. 41% of staff had received
      training specifically on transfusion consent in the last 2 years. CONCLUSIONS:
      There is a need to improve clinical practice in obtaining valid consent for
      transfusion in line with existing national guidelines and local Trust policies,
      with emphasis on documentation within clinical records. Provision of patient
      information is an area particularly highlighted for action, and transfusion
      training for clinicians should be strengthened.

PMID- 29193376
TI  - Evaluation of left ventricular reverse remodeling in patients with severe aortic
      regurgitation undergoing aortic valve replacement: Comparison between diameters
      and volumes.
AB  - BACKGROUND: In patients with severe aortic regurgitation (AR), the left
      ventricular ejection fraction (LVEF) and left ventricle (LV) size are crucial for
      determining clinical prognosis and timing of valve intervention. In clinical
      practice, LV internal diameters obtained at end-diastole are used to assess the
      degree of LV dilatation. Whether quantification of LV volumes would provide more
      robust information as compared to LV linear dimensions is unknown. METHODS: We
      retrospectively analyzed preoperative and postoperative transthoracic
      echocardiograms of patients who underwent aortic valve replacement (AVR) for
      severe AR. Indexed linear LV end-diastolic and end-systolic diameters along with
      indexed LV end-diastolic and end-systolic volumes were obtained as per current
      guidelines. Post-AVR LV reverse remodeling, defined as >=10% reduction in
      measures of LV volumes (Teichholz and Simpson's methods), was determined.
      Positive and negative agreement was calculated between the volume- and diameter
      based LV reverse remodeling. RESULTS: Sixty-two consecutive patients were
      included. Nine patients (17%) without LV reverse remodeling based on Teichholz
      were reclassified as having LV reverse remodeling based on Simpson (positive
      agreement 0.846 [95% CI 0.772, 0.921], negative agreement 0.200 [95% CI -0.350,
      0.435]). Left ventricle (LV) reverse remodeling assessed by the Teichholz method
      was underestimated by a mean of 31 mL/m2 (beta = -0.65 [95% CI -1.06 to -0.24], P
      = .003) compared to Simpson method. CONCLUSION: Compared to the volume-based
      method, diameter-based LV measurement incorrectly identified LV reverse
      remodeling post-AVR in 17% of patients with severe AR. Left ventricle (LV) volume
      may be a better measure to assess LV remodeling post-AVR than LV diameter-based
      measurements.

PMID- 29193377
TI  - Evaluation of a new fluorescent reagent, fluorescent brightener 85, for the
      diagnosis of suspected onychomycosis compared with potassium hydroxide.
AB  - Onychomycosis is a common fungal infection in dermatology clinics. The commonly
      used diagnostic method, potassium hydroxide (KOH) direct microscopy, does not
      have a high-positive detection rate. Therefore, a new diagnostic method is needed
      to confirm onychomycosis. The objective of this research was to use fluorescent
      brightener 85 (FB 85), a new fluorescent reagent for fungi detection, and to
      evaluate this new method based on the diagnostic positive rate, accuracy and
      efficiency in suspected onychomycosis compared with the KOH method. Subungual
      debris was collected from clinically suspected onychomycosis cases and divided
      into two parts. The parts were examined by FB 85 and 10% KOH solution,
      respectively. In total, 108 patients with suspected onychomycosis were recruited.
      The positive rates of FB 85 and KOH were 88.9% and 55.6%, respectively. The
      patients showed significant statistical differences (P < .001). Compared with the
      KOH method, the FB 85 fluorescent method was an accurate and efficient method
      with a higher positive rate. This method could increase the diagnostic accuracy
      and efficiency of onychomycosis detection.

PMID- 29193378
TI  - Acid-Triggered O-O Bond Heterolysis of a Nonheme FeIII (OOH) Species for the
      Stereospecific Hydroxylation of Strong C-H Bonds.
AB  - A novel hydroperoxoiron(III) species [FeIII (OOH)(MeCN)(PyNMe3 )]2+ (3) has been
      generated by reaction of its ferrous precursor [FeII (CF3 SO3 )2 (PyNMe3 )] (1)
      with hydrogen peroxide at low temperatures. This species has been characterized
      by several spectroscopic techniques and cryospray mass spectrometry. Similar to
      most of the previously described low-spin hydroperoxoiron(III) compounds, 3
      behaves as a sluggish oxidant and it is not kinetically competent for breaking
      weak C-H bonds. However, triflic acid addition to 3 causes its transformation
      into a much more reactive compound towards organic substrates that is capable of
      oxidizing unactivated C-H bonds with high stereospecificity. Stopped-flow kinetic
      analyses and theoretical studies provide a rationale for the observed chemistry,
      a triflic-acid-assisted heterolytic cleavage of the O-O bond to form a putative
      strongly oxidizing oxoiron(V) species. This mechanism is reminiscent to that
      observed in heme systems, where protonation of the hydroperoxo intermediate leads
      to the formation of the high-valent [(Porph. )FeIV (O)] (Compound I).

PMID- 29193379
TI  - Online education improves pediatric residents' understanding of atopic
      dermatitis.
AB  - BACKGROUND/OBJECTIVES: Pediatricians manage skin conditions such as atopic
      dermatitis (AD) but report that their dermatologic training is inadequate. Online
      modules may enhance medical education when sufficient didactic or clinical
      teaching experiences are lacking. We assessed whether an online module about AD
      improved pediatric residents' knowledge and changed their clinical management of
      AD. METHODS: Target and control cohorts of pediatric residents from two
      institutions were recruited. Target subjects took a 30-question test about AD
      early in their residency, reviewed the online module, and repeated the test 6
      months and 1 year later. The control subjects, who had 1 year of clinical
      experience but had not reviewed the online module, also took the test. The mean
      percentage of correct answers was calculated and compared using two-sided, two
      sample independent t tests and repeated-measures analysis of variance. For a
      subset of participants, clinical documentation from AD encounters was reviewed
      and 13 practice behaviors were compared using the Fisher exact test. RESULTS:
      Twenty-five subjects in the target cohort and 29 subjects in the control cohort
      completed the study. The target cohort improved from 18.0 +/- 3.2 to 23.4 +/- 3.4
      correctly answered questions over 1 year (P < .001). This final value was greater
      than that of the control cohort (20.7 +/- 4.5; P = .01). Meaningful differences
      in practice behaviors were not seen. CONCLUSION: Pediatric residents who reviewed
      an online module about AD demonstrated statistically significant improvement in
      disease-specific knowledge over time and had statistically significantly higher
      scores than controls. Online dermatology education may effectively supplement
      traditional clinical teaching.

PMID- 29193380
TI  - Optimization and validation of accelerated golden-angle radial sparse MRI
      reconstruction with self-calibrating GRAPPA operator gridding.
AB  - PURPOSE: Golden-angle radial sparse parallel (GRASP) MRI reconstruction requires
      gridding and regridding to transform data between radial and Cartesian k-space.
      These operations are repeatedly performed in each iteration, which makes the
      reconstruction computationally demanding. This work aimed to accelerate GRASP
      reconstruction using self-calibrating GRAPPA operator gridding (GROG) and to
      validate its performance in clinical imaging. METHODS: GROG is an alternative
      gridding approach based on parallel imaging, in which k-space data acquired on a
      non-Cartesian grid are shifted onto a Cartesian k-space grid using information
      from multicoil arrays. For iterative non-Cartesian image reconstruction, GROG is
      performed only once as a preprocessing step. Therefore, the subsequent iterative
      reconstruction can be performed directly in Cartesian space, which significantly
      reduces computational burden. Here, a framework combining GROG with GRASP (GROG
      GRASP) is first optimized and then compared with standard GRASP reconstruction in
      22 prostate patients. RESULTS: GROG-GRASP achieved approximately 4.2-fold
      reduction in reconstruction time compared with GRASP (~333 min versus ~78 min)
      while maintaining image quality (structural similarity index ~ 0.97 and root mean
      square error ~ 0.007). Visual image quality assessment by two experienced
      radiologists did not show significant differences between the two reconstruction
      schemes. With a graphics processing unit implementation, image reconstruction
      time can be further reduced to approximately 14 min. CONCLUSION: The GRASP
      reconstruction can be substantially accelerated using GROG. This framework is
      promising toward broader clinical application of GRASP and other iterative non
      Cartesian reconstruction methods. Magn Reson Med 80:286-293, 2018. (c) 2017
      International Society for Magnetic Resonance in Medicine.

PMID- 29193381
TI  - Experiences of older people following an acute exacerbation of chronic
      obstructive pulmonary disease: A phenomenological study.
AB  - AIMS AND OBJECTIVES: To explore the experience of patients affected by chronic
      obstructive pulmonary disease following hospitalisation due to an acute
      exacerbation event. BACKGROUND: Chronic obstructive pulmonary disease is a
      progressively debilitating disease, often with very burdensome symptoms such as
      acute and chronic breathlessness and fatigue. Acute exacerbation often creates a
      life-threatening event. Exacerbation can also have substantial psychological
      effects including anxiety and depression although this aspect is less well
      researched-especially amongst people with chronic obstructive pulmonary disease
      recovering from an acute event and facing a return home. DESIGN: A descriptive
      phenomenological study. METHODS: In-depth interviews were conducted with 12
      chronic obstructive pulmonary disease patients recently recovering from an acute
      exacerbation of their chronic obstructive pulmonary disease. Data were analysed
      using Colaizzi's phenomenological framework. RESULTS: Four themes were identified
      from the data: a sense of loss and frustration, hopelessness, uncertainty about
      the future and fear of becoming a burden. Participants expressed quite negative
      views including a loss of hope, uncertainty about their future care and the
      burden they may become on their families. They appeared stressed and anxious as a
      result of the acute event they had experienced. CONCLUSIONS: This study shows
      that an acute episode of illness can generate a sense of hopelessness and
      uncertainty about their future care in people with chronic obstructive pulmonary
      disease. This occurs as they recover physically and think about the future, often
      in quite negative terms. RELEVANCE TO CLINICAL PRACTICE: For healthcare
      professionals, it is important to take into account the potential feelings of
      loss, hopelessness and uncertainty that people can experience following an acute
      exacerbation of their chronic obstructive pulmonary disease and ensure that
      psychological care is available as physical recovery takes place. Such care to
      include good discharge planning, giving patients time to express concerns and
      referral to counselling services if appropriate.

PMID- 29193383
TI  - Blood transfusion is a critical determinant of resource utilization and total
      hospital cost in liver transplantation.
AB  - OBJECTIVE: The aim of this study is to identify factors associated with increased
      resource use and total hospital cost (THC) after liver transplantation (LT).
      METHODS: A study of LT patients undergoing surgery between January 2008 and
      December 2013 was performed. Main end points were LOS, intensive care unit length
      of stay (ICU LOS), days on the ventilator, THCs, service area costs. RESULTS: A
      total of 191 patients undergoing LT were included in the analysis. Creatinine and
      blood transfusion were significantly associated with prolonged LOS, ICU LOS, and
      days on the ventilator. Multivariable analysis of predictors of THC demonstrated
      creatinine as a strong pre-operative factor. Creatinine was also a significant
      predictor of OR, ICU, pharmacy, in-patient (floor), diagnostics, and ancillary
      services cost. After controlling for intra-operative factors such as operative
      time and blood transfusions, we found that transfusions were the strongest
      independent predictors of total cost. Patients receiving <5 units of PRBCs had a
      median LOS of 7 days. ICU LOS doubled and ICU total cost increased by 50% if
      patients required more than five transfusions of PRBCs. CONCLUSIONS: Elevated
      serum creatinine and blood transfusions are the most critical determinants of
      increased resource utilization and hospital expenditure in LT.

PMID- 29193382
TI  - Prediction of no-reflow and major adverse cardiovascular events with a new
      scoring system in STEMI patients.
AB  - BACKGROUND: No-reflow is associated with a poor prognosis in STEMI patients.
      There are many factors and mechanisms that contribute to the development of no
      reflow, including age, reperfusion time, a high thrombus burden, Killip class,
      long stent use, ejection fraction <=40, and a high Syntax score. In this study,
      we aimed to evaluate the parameters associated with no-reflow prediction by
      creating a new scoring system. METHODS: The study included 515 consecutive STEMI
      patients who underwent PCI; 632 STEMI patients who had undergone PCI in another
      center were included in the external validation of the scoring system. The
      correlations between 1-year major adverse cardiac events and low/high risk score
      were assessed. RESULTS: In this study, seven independent variables were used to
      build a risk score for predicting no-reflow. The predictors of no-reflow are age,
      EF <=40, SS >=22, stent length >=20, thrombus grade >=4, Killip class >=3, and
      pain-balloon time >=4 h. In the derivation group, the optimal threshold score for
      predicting no-reflow was >10, with a 75% sensitivity and 77.7% specificity (Area
      under the curve (AUC) = 0.809, 95%CI: 0.772-0.842, P < 0.001). In the validation
      group, AUC was 0.793 (95%CI: 0.760-0.824, P < 0.001). CONCLUSION: This new score,
      which can be calculated in STEMI patients before PCI and used to predict no
      reflow in STEMI patients, may help physicians to estimate the development of no
      reflow in the pre-PCI period.

PMID- 29193384
TI  - Concurrent isotope-assisted metabolic flux analysis and transcriptome profiling
      reveal responses of poplar cells to altered nitrogen and carbon supply.
AB  - Reduced nitrogen is indispensable to plants. However, its limited availability in
      soil combined with the energetic and environmental impacts of nitrogen
      fertilizers motivates research into molecular mechanisms toward improving plant
      nitrogen use efficiency (NUE). We performed a systems-level investigation of this
      problem by employing multiple 'omics methodologies on cell suspensions of hybrid
      poplar (Populus tremula * Populus alba). Acclimation and growth of the cell
      suspensions in four nutrient regimes ranging from abundant to deficient supplies
      of carbon and nitrogen revealed that cell growth under low-nitrogen levels was
      associated with substantially higher NUE. To investigate the underlying metabolic
      and molecular mechanisms, we concurrently performed steady-state 13 C metabolic
      flux analysis with multiple isotope labels and transcriptomic profiling with cDNA
      microarrays. The 13 C flux analysis revealed that the absolute flux through the
      oxidative pentose phosphate pathway (oxPPP) was substantially lower (~threefold)
      under low-nitrogen conditions. Additionally, the flux partitioning ratio between
      the tricarboxylic acid cycle and anaplerotic pathways varied from 84%:16% under
      abundant carbon and nitrogen to 55%:45% under deficient carbon and nitrogen. Gene
      expression data, together with the flux results, suggested a plastidic
      localization of the oxPPP as well as transcriptional regulation of certain
      metabolic branchpoints, including those between glycolysis and the oxPPP. The
      transcriptome data also indicated that NUE-improving mechanisms may involve a
      redirection of excess carbon to aromatic metabolic pathways and extensive
      downregulation of potentially redundant genes (in these heterotrophic cells) that
      encode photosynthetic and light-harvesting proteins, suggesting the recruitment
      of these proteins as nitrogen sinks in nitrogen-abundant conditions.

PMID- 29193385
TI  - A General Asymmetric Formal Synthesis of Aza-Baylis-Hillman Type Products under
      Bifunctional Catalysis.
AB  - A new organocatalytic strategy for the synthesis of enantioenriched aza-Baylis
      Hillman type products via a frustrated vinylogous reaction is presented. This
      process proceeds under mild conditions with good yields, completed Z/E
      selectivity and excellent enantioselectivities. Moreover, easy derivatizations of
      the final products led to important building blocks of organic synthesis such as
      1,3-aminoalcohols and Lewis base catalysts.

PMID- 29193386
TI  - On the Structure and Reaction Mechanism of Human Acireductone Dioxygenase.
AB  - Acireductone dioxygenase (ARD) is an intriguing enzyme from the methionine
      salvage pathway that is capable of catalysing two different oxidation reactions
      with the same substrate depending on the type of the metal ion in the active
      site. To date, the structural information regarding the ARD-acireductone complex
      is limited and possible reaction mechanisms are still under debate. The results
      of joint experimental and computational studies undertaken to advance knowledge
      about ARD are reported. The crystal structure of an ARD from Homo sapiens was
      determined with selenomethionine. EPR spectroscopy suggested that binding
      acireductone triggers one protein residue to dissociate from Fe2+ , which allows
      NO (and presumably O2 ) to bind directly to the metal. Mossbauer spectroscopic
      data (interpreted with the aid of DFT calculations) was consistent with bidentate
      binding of acireductone to Fe2+ and concomitant dissociation of His88 from the
      metal. Major features of Fe vibrational spectra obtained for the native enzyme
      and upon addition of acireductone were reproduced by QM/MM calculations for the
      proposed models. A computational (QM/MM) study of the reaction mechanisms
      suggests that Fe2+ promotes O-O bond homolysis, which elicits cleavage of the C1
      C2 bond of the substrate. Higher M3+ /M2+ redox potentials of other divalent
      metals do not support this pathway, and instead the reaction proceeds similarly
      to the key reaction step in the quercetin 2,3-dioxygenase mechanism.

PMID- 29193387
TI  - The nuclear hormone receptor E75A regulates vitellogenin gene (Al-Vg) expression
      in the mirid bug Apolygus lucorum.
AB  - Apolygus lucorum is the predominant pest of Bacillus thuringiensis (Bt) cotton in
      China. 20-hydroxyecdysone (20E) plays a key role in the reproduction of this
      insect. To better understand the mechanism underlying 20E-regulated reproduction,
      the nuclear hormone receptor E75 isoform-A of Ap. lucorum (Al-E75A) was cloned
      and its expression analysed. A 2241-bp sequence of Al-E75A cDNA encoded an open
      reading frame of a polypeptide with a predicted molecular mass of 69.04 kDa. Al
      E75A mRNA was detected in female adult stages of Ap. lucorum with peak expression
      in 7-day-old animals. Al-E75A was also expressed in several tissues, particularly
      in the fat body and ovary. A 3.2 kb Al-E75A mRNA was detected in all tissues by
      Northern blot. The fecundity and longevity were significantly decreased in female
      adults treated with Al-E75A small interfering RNA. The rates of egg incubation
      rates were considerably lower in the RNA interference-treated animals compared to
      the untreated controls. In order to investigate the molecular mechanism
      underlying the effects described above, vitellogenin (Al-Vg) was selected for
      further investigation. The expression pattern of Al-Vg was similar to that of Al
      E75A and was up-regulated by 20E. After knockdown of Al-E75A, the expression
      profile of Al-Vg and the protein levels were down-regulated. These findings
      suggest that Al-E75A plays a crucial role in the regulation of Al-Vg expression
      in Ap. lucorum.

PMID- 29193388
TI  - The associations of illness perception with metabolic control (HbA1c) among type
      2 diabetes mellitus patients in a district hospital.
AB  - OBJECTIVES: Despite the availability of a wide selection of anti-diabetic
      treatments, many type 2 DM (T2DM) patients still do not have controlled glucose
      levels. In addition to pharmacological intervention, patients' own implicit
      beliefs about their illness should be targeted for health intervention. Thus, we
      conducted a quantitative study to evaluate the associations between illness
      perception (IP) domains and metabolic control (HbA1c) of T2DM patients in Selama
      Hospital and to identify patients' perceptions of the causal T2DM factors.
      METHOD: A cross-sectional study was conducted in the outpatient department of
      Selama Hospital from October to December 2015. A total of 200 T2DM patients were
      recruited using systematic random sampling. A self-administered validated
      questionnaire consisting of three sections was used, and the data were analysed
      using SPSS version 18. The associations between eight IP domains and HbA1c were
      evaluated via multiple linear regression. P values <0.05 were considered
      significant. KEY FINDINGS: The analysis included data from 200 respondents with a
      mean age of 57.7 years (SE = 9.8). The majority were women (64.5%) and Malays
      (86%) with a primary school education (43.5%) and a family history of diabetes
      (53.5%). The median duration of illness was 5 years (IQR = 7), and the median
      HbA1c level was 8.15% (IQR = 3.1). The mean score for the eight IP domains was
      33.7 (SE = 8.43) out of a total score of 80. Using multiple linear regression,
      HbA1c was found to be significantly associated with IP domains of identity
      symptoms at 0.221 (95% CI 0.083-0.358). Moreover, 79.4% of patients ranked diet
      and eating behaviour as the main factor for T2DM. CONCLUSION: The IP domain of
      identity symptoms was significantly correlated with T2DM metabolic control. By
      understanding patients' IP, healthcare providers can focus on behavioural
      approaches to managing T2DM patients. Steps must be taken to educate patients
      about the importance of diet control in managing T2DM.

PMID- 29193389
TI  - Antimicrobial activity of copaiba oil (Copaifera ssp.) on oral pathogens:
      Systematic review.
AB  - Copaifera ssp. produces an oil-resin that presents antiinflammatory, antitumor,
      antiseptic, germicidal, antifungal, and antibacterial activity. This systematic
      review aimed to analyze the antimicrobial action of Copaiba oil against oral
      pathogens, when compared to that of control substances. A search on
      Medline/PubMed, LILACS, SciELO, EMBASE, and SCOPUS databases were performed up to
      March 2017. To be included, the studies needed to perform any antimicrobial
      activity essay, using copaiba oil and a control substance. The antimicrobial
      effect of each substance, in each study, was extracted. Eleven studies were
      included, and several copaiba species were used. All studies showed that copaiba
      oil, regardless of its species, presented a bactericidal and/or bacteriostatic
      effect in in vitro analyzes. Only one study showed that the antimicrobial effect
      of the Copaifera officinalis was similar to the one found in chlorhexidine. A
      higher risk of bias was detected in most of the included studies. The studies
      demonstrated that the antimicrobial activity of copaiba oil, in most cases, is
      lower than chlorhexidine, which is considered the gold standard. However, there
      is great potential against oral bacteria. Further high quality studies are
      warranted in order to assess the efficacy of copaiba oil on oral pathogens.

PMID- 29193390
TI  - Lonicera japonica Thunb. Induces caspase-dependent apoptosis through death
      receptors and suppression of AKT in U937 human leukemic cells.
AB  - Decoctions obtained from the dried flowers of Lonicera japonica Thunb.
      (Indongcho) have been utilized in folk remedies against inflammatory diseases.
      Recently, many agents that have used for inflammatory diseases are showing
      anticancer effects. Here, we have isolated polyphenols extracted from lyophilized
      Lonicera japonica Thunb (PELJ) and investigated the anticancer effects of PELJ on
      U937 cells. Here, we demonstrated that PELJ induced apoptosis by upregulation of
      DR4 and Fas, and further it is augmented by suppression of XIAP. In addition, The
      PELJ-induced apoptosis is at least in part by blocking PI3K/Akt pathway. These
      findings suggest that PELJ may provide evidence of anticancer activities on U937
      cells. Further study for detailed mechanism and the effects on animal models is
      warranted to determine whether PELJ provide more conclusive evidence that PELJ
      which may provide a beneficial effect for treating cancer.

PMID- 29193392
TI  - Ancient chromosomal rearrangement associated with local adaptation of a
      postglacially colonized population of Atlantic Cod in the northwest Atlantic.
AB  - Intraspecific diversity is central to the management and conservation of
      exploited species, yet knowledge of how this diversity is distributed and
      maintained in the genome of many marine species is lacking. Recent advances in
      genomic analyses allow for genome-wide surveys of intraspecific diversity and
      offer new opportunities for exploring genomic patterns of divergence. Here, we
      analysed genome-wide polymorphisms to measure genetic differentiation between an
      offshore migratory and a nonmigratory population and to define conservation units
      of Atlantic Cod (Gadus morhua) in coastal Labrador. A total of 141 individuals,
      collected from offshore sites and from a coastal site within Gilbert Bay,
      Labrador, were genotyped using an ~11k single nucleotide polymorphism array.
      Analyses of population structure revealed strong genetic differentiation between
      migratory offshore cod and nonmigratory Gilbert Bay cod. Genetic differentiation
      was elevated for loci within a chromosomal rearrangement found on linkage group 1
      (LG1) that coincides with a previously found double inversion associated with
      migratory and nonmigratory ecotype divergence of cod in the northeast Atlantic.
      This inverted region includes several genes potentially associated with
      adaptation to differences in salinity and temperature, as well as influencing
      migratory behaviour. Our work provides evidence that a chromosomal rearrangement
      on LG1 is associated with parallel patterns of divergence between migratory and
      nonmigratory ecotypes on both sides of the Atlantic Ocean.

PMID- 29193391
TI  - Dihydromyricetin inhibits NLRP3 inflammasome-dependent pyroptosis by activating
      the Nrf2 signaling pathway in vascular endothelial cells.
AB  - Increasing evidence demonstrates that pyroptosis, pro-inflammatory programmed
      cell death, is linked to atherosclerosis; however, the underlying mechanisms
      remain to be elucidated. Dihydromyricetin (DHM), a natural flavonoid, was
      reported to exert anti-oxidative and anti-inflammatory bioactivities. However,
      the effect of DHM on atherosclerosis-related pyroptosis has not been studied. In
      the present study, palmitic acid (PA) treatment led to pyroptosis in human
      umbilical vein endothelial cells (HUVECs), as evidenced by caspase-1 activation,
      LDH release, and propidium iodide-positive staining; enhanced the maturation and
      release of proinflammatory cytokine IL-1beta and activation of the NLRP3
      inflammasome; and markedly increased intracellular reactive oxygen species (ROS)
      and mitochondrial ROS (mtROS) levels. Moreover, NLRP3 siRNA transfection or
      treatment with inhibitors efficiently suppressed PA-induced pyroptosis, and
      pretreatment with total ROS scavenger or mtROS scavenger attenuated PA-induced
      NLRP3 inflammasome activation and subsequent pyroptosis. However, DHM
      pretreatment inhibited PA-induced pyroptotic cell death by increasing cell
      viability, decreasing LDH and IL-1beta release, improving cell membrane
      integrity, and abolishing caspase-1 cleavage and subsequent IL-1beta maturation.
      We also found that DHM pre-treatment remarkably reduced the levels of
      intracellular ROS and mtROS and activated the Nrf2 signaling pathway. Moreover,
      knockdown of Nrf2 by siRNA abrogated the inhibitory effects of DHM on ROS
      generation and subsequent PA-induced pyroptosis. Together, these results indicate
      that the Nrf2 signaling pathway plays a role, as least in part, in the DHM
      mediated improvement in PA-induced pyroptosis in vascular endothelial cells,
      which implies the underlying medicinal value of DHM targeting immune/inflammatory
      related diseases, such as atherosclerosis. (c) 2017 BioFactors, 44(2):123-136,
      2018.

PMID- 29193394
TI  - Direct Correlation of Excitonics with Efficiency in a Core-Shell Quantum Dot
      Solar Cell.
AB  - Shell thickness dependent band-gap engineering of quasi type II core-shell
      material with higher carrier cooling time, lower interfacial defect states, and
      longer charge carrier recombination time can be a promising candidate for both
      photocatalysis and solar cell. In the present investigation, colloidal CdSe@CdS
      core-shells with different shell thickness (2, 4 and 6 monolayer CdS) were
      synthesized through hot injection method and have been characterized by high
      resolution transmission electron microscope (HRTEM) followed by steady state
      absorption and luminescence techniques. Ultrafast transient absorption (TA)
      studies suggest longer carrier cooling, lower interfacial surface states, and
      slower carrier recombination time in CdSe@CdS core-shell with increasing shell
      thickness. By TA spectroscopy, the role of CdS shell in power conversion
      efficiency (PCE) has been explained in detail. The measured PCE was found to
      initially increase and then decrease with increasing shell thickness. Shell
      thickness has been optimized to maximize the efficiency after correlating the
      shell controlled carrier cooling and recombination with PCE values and a maximum
      PCE of 3.88 % was obtained with 4 monolayers of CdS shell, which is found to be
      57 % higher than compared to bare CdSe QDs.

PMID- 29193393
TI  - Modified first or second cervical nerve transplantation technique for the
      treatment of recurrent laryngeal neuropathy in horses.
AB  - BACKGROUND: In horses, the only established method for reinnervation of the
      larynx is the nerve-muscle pedicle implantation, whereas in human medicine,
      direct nerve implantation is a standard surgical technique for selective
      laryngeal reinnervation in human patients suffering from bilateral vocal fold
      paralysis. OBJECTIVES: (1) To describe a modified first or second cervical nerve
      transplantation technique for the treatment of recurrent laryngeal neuropathy
      (RLN) in horses and (2) evaluate the outcomes of reinnervation using direct nerve
      needle-stimulation of the first cervical nerve and exercising endoscopy before
      and after surgery. STUDY DESIGN: Case series. METHODS: Nerve transplantation
      surgery, in which the first or second cervical nerve is tunnelled through the
      atrophied left cricoarytenoideus dorsalis muscle, was performed in combination
      with ipsilateral laser ventriculocordectomy. Ultrasound-guided stimulation of the
      first cervical nerve at the level of the alar foramen was used to confirm
      successful reinnervation post-operatively. Exercising endoscopy was performed
      before and after surgery. The exercising RLN grade of the left arytenoid was
      blindly determined at the highest stride frequency for each examination. RESULTS:
      Surgery was performed in 17 client-owned animals with RLN. Reinnervation was
      confirmed by nerve stimulation and subsequent arytenoid abduction observed in 11
      out of 12 cases between 4 and 12 months post-operatively. Fourteen horses had
      exercising endoscopy before and after surgery. Nine horses had an improved
      exercising RLN grade, four horses had the same exercising grade and one horse had
      a worse exercising grade after surgery. MAIN LIMITATIONS: A sham-operated control
      group was not included and follow-up beyond 12 months and objective performance
      data were not obtained. CONCLUSIONS: The modified first or second cervical nerve
      transplantation technique, using tunnelling and direct implantation of the donor
      nerve into the cricoarytenoideus dorsalis muscle, resulted in reinnervation in 11
      out of 12 cases and improved exercising grade in 9 out of 14 horses within 12
      months after surgery.

PMID- 29193396
TI  - Recent Advances in Metallaaromatic Chemistry.
AB  - Metallaaromatics can be broadly defined as aromatic compounds in which one of the
      ring atoms is a transition metal. The metallabenzenes are one important class of
      these compounds that has undergone extensive study recently. Closely related
      species such as fused-ring metallabenzenes, heterometallabenzenes, pi-coordinated
      metallabenzenes and metallabenzynes have also attracted considerable attention.
      Although many metallaaromatics can be considered as metalla-analogues of classic
      organic aromatic compounds, this is not always the case. Recent seminal studies
      have shown that metallapentalenes and metallapentalynes, which are metalla
      analogues of the anti-aromatic compounds pentalene and pentalyne, are in fact
      aromatic and highly stable. Very unusual spiro-metallaaromatic compounds have
      also recently been isolated. In this concepts article, key features of all these
      intriguing metallaaromatic compounds are discussed with reference to the
      structural, spectroscopic, reactivity and theoretical studies that have been
      undertaken. These compounds continue to generate much interest, not only because
      of the contributions they make to fundamental chemical understanding, but also
      because of the promise of possible practical applications.

PMID- 29193395
TI  - Androgen and oestrogen receptors as potential prognostic markers for patients
      with ductal carcinoma in situ treated with surgery and radiotherapy.
AB  - Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has been
      investigated less extensively than invasive breast cancer. Women with DCIS are
      mainly treated with conservative surgery almost exclusively followed by
      radiotherapy. However, as radiation treatment is not always effective, the search
      for biomarkers capable of identifying DCIS lesions that could progress to
      invasive cancer is ongoing. Although conventional biomarkers have been thoroughly
      studied in invasive tumours, little is known about the role played by androgen
      receptor (AR), widely expressed in DCIS. A series of 42 DCIS patients treated
      with quadrantectomy and radiotherapy were followed for a period of up to 95
      months. Of these, 11 had recurrent DCIS or progressed to invasive cancer. All
      tumours were analysed for clinical pathological features. Conventional biomarkers
      and androgen receptor expression were determined by immunohistochemistry. Our
      results showed that AR was higher in tumours of relapsed patients than non
      relapsed patients (P value: 0.0005). Conversely, oestrogen receptor (ER) was
      higher, albeit not significantly, in non-relapsed patients than in relapsed
      patients. AR/ER ratio was considerably different in the two subgroups (P value:
      0.0033). Area under the curve (AUC) values were 0.85 for AR and 0.80 for the
      AR/ER ratio. These preliminary results highlight the potentially important role
      of both AR and the AR/ER ratio as prognostic markers in DCIS.

PMID- 29193397
TI  - Nurses' preparedness for infectious disease outbreaks: A literature review and
      narrative synthesis of qualitative evidence.
AB  - AIMS AND OBJECTIVES: To explore the core components that constitute nurses'
      preparedness in an epidemic event. BACKGROUND: Healthcare service providers have
      worked to augment efforts to protect the public from the impact of epidemic
      events. While constituting the major healthcare taskforce, nurses are frequently
      tasked with fronting the response to an infectious disease outbreak. Given the
      crucial role of nurses in the management of prevailing epidemics, the
      constituents of their preparedness in epidemic events should be identified.
      DESIGN: A systematic search was undertaken to identify eligible studies from the
      literature. A narrative synthesis approach was employed to extract and synthesise
      findings of the reviewed qualitative studies. METHODS: Seven qualitative studies
      on nurses' experience and perceptions of epidemic events were examined for
      scientific quality using the Critical Appraisal Skills Programme Qualitative
      Checklist. Findings of these studies were synthesised adopting a narrative
      synthesis approach. RESULTS: Three interplaying themes were identified as
      follows: (i) personal resources, (ii) workplace resources and (iii) situational
      influences. The findings suggest that an effective epidemic outbreak response
      would require further effort to reinforce the interplay between individual
      nurses, healthcare institutions and the governments. CONCLUSIONS: The practical
      interplay among individual nurses, healthcare institutions and the governments is
      crucial in establishing an effective epidemic response. Further research on the
      understanding of the dynamic process of preparedness development is recommended
      to set future directions in research. RELEVANCE TO CLINICAL PRACTICE: This study
      offers important insights for devising future strategies in enhancing nurses'
      preparedness and response to an epidemic event. These include recommendations on
      providing education and training to nurses regarding infectious diseases,
      fostering institutional assistance and support in an outbreak and revising
      government policies and planning.

PMID- 29193398
TI  - Characterization at the Level of Individual Crystals: Single-Crystal MFI Type
      Zeolite Grains.
AB  - Electron-diffraction data on the zeolites Silicalite-1 and ZSM-5 (both MFI
      framework type) were collected from individual grains of about 150*100*50 nm3 .
      Crystals were synthesized with tetrapropylammonium as structure-directing agent.
      The resolution extended to about 0.8 A for Silicalite-1 and about 0.9-1.0 A for
      ZSM-5 crystals. Analysis of several data sets showed that at the nanometre-scale,
      these zeolite crystals are single crystals and not intergrown.

PMID- 29193399
TI  - Quality improvement of physical health monitoring for people with intellectual
      disabilities: an integrative review.

PMID- 29193400
TI  - Classifying tremor: Language matters.

PMID- 29193401
TI  - Tonsillectomy and risk of Parkinson's disease: A danish nationwide population
      based cohort study.
AB  - BACKGROUND: We hypothesized that tonsillectomy modifies the risk of PD.
      OBJECTIVES: To test the hypothesis in a nationwide population-based cohort study.
      METHODS: We used Danish medical registries to construct a cohort of all patients
      in Denmark with an operation code of tonsillectomy 1980-2010 (n = 195,169) and a
      matched age and sex general population comparison cohort (n = 975,845). Patients
      were followed until PD diagnosis, death, censoring, or end of follow-up 30
      November 2013. Using Cox regression, we computed hazard ratios for PD and
      corresponding 95% confidence intervals, adjusting for age and sex by study
      design, and potential confounders. RESULTS: We identified 100 and 568 patients
      diagnosed with PD among the tonsillectomy and general population comparison
      cohort, respectively, finding similar risks of PD (adjusted hazard ratio = 0.95
      [95% confidence interval: 0.76-1.19]; for > 20 years' follow-up (adjusted hazard
      ratio = 0.96 [95% confidence interval: 0.64-1.41]). CONCLUSION: Tonsillectomy is
      not associated with risk of PD, especially early-onset PD. (c) 2017 International
      Parkinson and Movement Disorder Society.

PMID- 29193403
TI  - A Redox-Active Bis(ferrocenyl)germylene and Its Reactivity.
AB  - Bis(ferrocenyl)germylene Fc*2 Ge: [2; Fc*=2,5-bis(3,5-di-tert-butylphenyl)-1
      ferrocenyl] was isolated in the form of red crystals from the reaction of the
      sterically demanding ferrocenyl lithium dimer (Fc*Li)2 and GeI2 .
      Bis(ferrocenyl)germylene 2 exhibits extraordinary thermal stability in
      hydrocarbon solution and the solid state, as well as stable redox behavior.
      Moreover, it undergoes a ligand-redistribution reaction with GeCl2 ?(dioxane) to
      afford the corresponding chlorogermylene, which was isolated upon coordination
      with PBu3 .

PMID- 29193402
TI  - Efficacy and safety of Tripterygium wilfordii Hook F for CKD in Mainland China: A
      systematic review and meta-analysis.
AB  - Tripterygium wilfordii Hook F (TwHF) is a promising Chinese traditional medicine
      used to significantly reduce proteinuria and improve renal function. However, its
      efficacy and safety in treatment of chronic kidney disease need to be further
      explored in order to promote its application in clinics. This review compared the
      efficacy and safety of TwHF with the placebo, conventional Western medicine and
      other immunosuppressive medicine in a range of kidney disorders. One hundred
      three randomized controlled trials were included. TwHF therapy decreased 24-hr
      proteinuria by 0.59 g/day (95% confidence interval [CI; -0.68, -0.50]), serum
      creatinine level by 1.93 MUmol/L (95% CI [-3.69, -0.17]), and blood urea nitrogen
      level by 0.24 mmol/L (95% CI [-0.41, -0.07]); increased the total effective rate
      by 27% (95% CI [1.24, 1.30]); and decreased the incidence of adverse reactions by
      19% (95% CI [0.68, 0.96]) overall. Meta regression results showed that the
      duration of therapy and mean age of participants were the major sources of high
      heterogeneity. Sensitivity analysis demonstrated that our statistic results were
      relatively stable and credible. The present findings suggested that TwHF possibly
      has nephroprotective effects by decreasing proteinuria, serum creatinine level,
      and blood urea nitrogen level and no more adverse reactions compared with control
      group in most kidney disorders. However, these findings still need to be further
      confirmed by high-quality trials.

PMID- 29193404
TI  - Surgical treatment of the residual periodontal pocket.
AB  - The ultimate goal of periodontal therapy is to prevent further disease
      progression in order to reduce the risk of tooth loss. This objective can be
      achieved through a number of therapeutic modalities comprising both the
      nonsurgical and surgical phases of periodontal therapy. Nonsurgical periodontal
      treatment has been shown to control periodontal infection and to arrest
      progression of the disease in a significant number of cases. However, despite
      completion of nonsurgical treatment, a number of periodontal pockets, defined as
      'residual', often remain. The presence of residual pockets may jeopardize tooth
      survival and be a risk factor of further disease progression, and ultimately
      tooth loss. Therefore, the aim of this review is to analyze the knowledge
      available on the indications for and the performance of periodontal surgical
      treatment of residual pockets in terms of 'traditional' (clinical,
      microbiological), patient-based and systemic health outcomes.

PMID- 29193405
TI  - Epigallocatechin-3-gallate enhances differentiation of acute promyelocytic
      leukemia cells via inhibition of PML-RARalpha and HDAC1.
AB  - The use of all-trans retinoic acid (ATRA) has dramatically improved the treatment
      and survival rate of patients with acute promyelocytic leukemia (APL). However,
      toxicity and resistance to this drug are major problems in the treatment of APL
      with ATRA. Earlier studies have suggested that the green tea polyphenol
      epigallocatechin gallate (EGCG) induces cell death in hematopoietic neoplasms
      without adversely affecting normal cells. In the present study, the potential
      therapeutic effect of EGCG in APL and the underlying molecular mechanisms were
      investigated. EGCG (100 MUM) significantly inhibited proliferation and induced
      apoptosis in HL-60 and NB4 cells. This effect was associated with decreased
      expressions of multidrug resistance proteins ABCB1, and ABCC1, whereas the
      expressions of pro-apoptotic genes CASP3, CASP8, p21, and Bax/Bcl-2 ratio were
      significantly increased. EGCG, at 25 MUM concentration, induced differentiation
      of leukemic cells towards granulocytic pattern in a similar manner to that
      observed for ATRA (1 MUM). Furthermore, EGCG suppressed the expression of
      clinical marker PML/RARalpha in NB4 cells and reduced the expression of HDAC1 in
      leukemic cells. In conclusion, the results suggested that EGCG can be considered
      as a potential treatment for APL.

PMID- 29193406
TI  - Online 1 H-MRS measurements of time-varying lactate production in an animal model
      of glioma during administration of an anti-tumoral drug.
AB  - The aims of this study were to implement a magnetic resonance spectroscopy (MRS)
      protocol for the online profiling of subnanomolar quantities of metabolites
      sampled from the extracellular fluid using implanted microdialysis and to apply
      this protocol in glioma-bearing rats for the quantification of lactate
      concentration and the measurement of time-varying lactate concentration during
      drug administration. MRS acquisitions on the brain microdialysate were performed
      using a home-built, proton-tuned, microsolenoid with an active volume of 2 MUL.
      The microcoil was placed at the outlet of the microdialysis probe inside a
      preclinical magnetic resonance imaging (MRI) scanner. C6-bearing rats were
      implanted with microdialysis probes perfused with artificial cerebrospinal fluid
      solution and the lactate dehydrogenase (LDH) inhibitor oxamate. Microcoil
      magnetic resonance spectra were continuously updated using a single-pulse
      sequence. Localized in vivo spectra and high-resolution spectra on the dialysate
      were also acquired. The limit of detection and limit of quantification per unit
      time of the lactate methyl peak were determined as 0.37 nmol/?min and 1.23
      nmol/?min, respectively. Signal-to-noise ratios (SNRs) of the lactate methyl peak
      above 120 were obtained from brain tumor microdialysate in an acquisition time of
      4 min. On average, the lactate methyl peak amplitude measured in vivo using the
      nuclear magnetic resonance (NMR) microcoil was 193 +/- 46% higher in tumor
      dialysate relative to healthy brain dialysate. A similar ratio was obtained from
      high-resolution NMR spectra performed on the collected dialysate. Following
      oxamate addition in the perfusate, a monotonic decrease in the lactate peaks was
      observed in all animals with an average time constant of 4.6 min. In the absence
      of overlapping NMR peaks, robust profiling of extracellular lactate can be
      obtained online using a dedicated sensitive NMR microcoil. MRS measurements of
      the dynamic changes in lactate production induced by anti-tumoral drugs can be
      assessed accurately with temporal resolutions on the order of minutes. The MRS
      protocol can be readily transferred to the clinical environment with the use of
      suitable clinical microdialysis probes.

PMID- 29193408
TI  - Threatened fertility: A longitudinal study exploring experiences of fertility and
      having children after cancer treatment.
AB  - Infertility is a recognised potential sequel of cancer treatment which impacts
      negatively on the quality of survival. The aim of this study was to explore how
      men and women experience the threat of infertility by cancer treatment and
      individuals' thoughts about having children after cancer during the first 2 years
      following diagnosis. Nine women and seven men (aged 24-41) participated in two
      interviews in this longitudinal interview study, after the initiation of cancer
      treatment and 2 years thereafter. The interviews focused on participants'
      thoughts and feelings about threatened fertility and having children. The
      interviews were analysed with qualitative content analysis with a particular
      focus on identifying experiences over time. The Traits-Desires-Intentions model
      was used to reflect upon the study findings. The analysis resulted in the
      identification of four themes: Continue calmly on chosen path, Abandoning plans
      for children, Avoiding the subject of fertility and Struggling towards life
      goals. The results emphasise the need to offer individualised fertility-related
      treatment communication and counselling, both at the time of cancer diagnosis and
      also in connection with follow-up care. Appropriate fertility-related
      communication should be included in young cancer patients' survivor care plans.

PMID- 29193407
TI  - Thermodynamic secrets of multidrug resistance: A new take on transport mechanisms
      of secondary active antiporters.
AB  - Multidrug resistance (MDR) presents a growing challenge to global public health.
      Drug extrusion transporters play a critical part in MDR; thus, their mechanisms
      of substrate recognition are being studied in great detail. In this work, we
      review common structural features of key transporters involved in MDR. Based on
      our membrane potential-driving hypothesis, we propose a general energy-coupling
      mechanism for secondary-active antiporters. This putative mechanism provides a
      common framework for understanding poly-specificity of most-if not all-MDR
      transporters.

PMID- 29193409
TI  - More insights into the pharmacological effects of artemisinin.
AB  - Artemisinin is one of the most widely prescribed drugs against malaria and has
      recently received increased attention because of its other potential biological
      effects. The aim of this review is to summarize recent discoveries of the
      pharmaceutical effects of artemisinin in basic science along with its mechanistic
      action, as well as the intriguing results of recent clinical studies, with a
      focus on its antitumor activity. Scientific evidence indicates that artemisinin
      exerts its biological activity by generating reactive oxygen species that damage
      the DNA, mitochondrial depolarization, and cell death. In the present article
      review, scientific evidence suggests that artemisinin is a potential therapeutic
      agent for various diseases. Thus, this review is expected to encourage interested
      scientists to conduct further preclinical and clinical studies to evaluate these
      biological activities.

PMID- 29193410
TI  - An integrative review of rural and remote nursing graduate programmes and
      experiences of nursing graduates.
AB  - AIMS AND OBJECTIVES: To examine international studies that specifically focus on
      transition to practice for graduate registered nurses in rural and remote areas.
      BACKGROUND: Supportive graduate nursing programmes are essential for enabling
      nursing graduates' transition to practice and reducing attrition rates.
      Literature examining support measures for nursing graduates within metropolitan
      areas is abundant. However, there is a paucity of evidence on effective graduate
      programmes for rural and remote-based nursing graduates. DESIGN: A systematic
      approach was used to identify robust research within appropriate electronic
      databases. METHOD: Eligible articles were critically reviewed using the Mixed
      Method Appraisal Tool critical appraisal tool. Eligible articles were
      thematically analysed using the Braun and Clark approach. RESULTS: Eight articles
      met the selection criteria for inclusion. Findings revealed that while most
      graduate nurses survived the transition process, they often felt overwhelmed and
      abandoned with intense feelings of frustration. Many suffered transition shock
      and did not feel ready for the role. Socialisation of graduates to the clinical
      environment was lacking. Support offered in many graduate programmes was ad hoc
      and unstructured. Senior staff were inadequately supported in their roles as
      preceptors to assist with the transition. Critical support measures recommended
      included both debrief sessions and regular one-on-one support. CONCLUSIONS:
      Graduate programmes need to be structured yet flexible to accommodate the needs
      of rural and remote nurse graduates. Graduates need to be transitioned into
      practice with decremental support processes for both workloads and education.
      Preceptors require education on how to mentor before they can provide the
      appropriate support for graduates. Without these measures in place, a decrease in
      transition shock may not be possible. RELEVANCE TO CLINICAL PRACTICE: Graduate
      programmes need to be structured yet flexible, including assistance with both
      clinical skills and socialisation. Senior staff require education before they can
      adequately support new graduates.

PMID- 29193411
TI  - A systematic review of the anti-obesity and weight lowering effect of ginger
      (Zingiber officinale Roscoe) and its mechanisms of action.
AB  - Recently, the beneficial effects of ginger on obesity is taken into
      consideration. Albeit, it seems that the anti-obesity effect of ginger and its
      mechanism of action has not yet been reviewed. Therefore, the aim of this study
      was to systematically review the effect of Zingiber officinale Roscoe on obesity
      management. Databases including PubMed, Scopus, Google scholar, and Science
      Direct were searched from 1995 until May 2017 using the definitive keywords.
      Searching was limited to articles with English language. All of the relevant
      human and animal studies and also in vitro studies were included. Review
      articles, abstract in congress, and also other varieties of ginger were excluded.
      Eligibility of included articles were evaluated by 3 reviewers, which also
      extracted data. Articles were critically assessed individually for possible risk
      of bias. Twenty-seven articles (6 in vitro, 17 animal, and 4 human studies) were
      reviewed. Most of the experimental studies supported the weight lowering effect
      of ginger extract or powder in obese animal models, whereas the results of the
      available limited clinical studies showed no changes or slight changes of
      anthropometric measurements and body composition in subjects with obesity. Ginger
      could modulate obesity through various potential mechanisms including increasing
      thermogenesis, increasing lipolysis, suppression of lipogenesis, inhibition of
      intestinal fat absorption, and controlling appetite. This review article provides
      some convincing evidence to support the efficacy of ginger in obesity management
      and demonstrates the importance of future clinical trials.

PMID- 29193412
TI  - Role of resveratrol in regulation of cellular defense systems against oxidative
      stress.
AB  - Resveratrol, a natural polyphenolic compound, is found in various kinds of
      fruits, plants, and their commercial products such as red wine. It has been
      demonstrated to exhibit a variety of health-promoting effects including
      prevention and/or treatment of cardiovascular diseases, inflammation, diabetes,
      neurodegeneration, aging, and cancer. Cellular defensive properties of
      resveratrol can be explained through its ability of either directly neutralizing
      reactive oxygen species/reactive nitrogen species (ROS/RNS) or indirectly
      upregulating the expression of cellular defensive genes. As a direct antioxidant
      agent, resveratrol scavenges diverse ROS/RNS as well as secondary organic
      radicals with mechanisms of hydrogen atom transfer and sequential proton loss
      electron transfer, thereby protecting cellular biomolecules from oxidative
      damage. Resveratrol also enhances the expression of various antioxidant defensive
      enzymes such as heme oxygenase 1, catalase, glutathione peroxidase, and
      superoxide dismutase as well as the induction of glutathione level responsible
      for maintaining the cellular redox balance. Such defenses could be achieved by
      regulating various signaling pathways including sirtuin 1, nuclear factor
      erythroid 2-related factor 2 and nuclear factor kappaB. This review provides
      current understanding and information on the role of resveratrol in cellular
      defense system against oxidative stress. (c) 2017 BioFactors, 44(1):36-49, 2018.

PMID- 29193413
TI  - Imaging brain microstructure with diffusion MRI: practicality and applications.
AB  - This article gives an overview of microstructure imaging of the brain with
      diffusion MRI and reviews the state of the art. The microstructure-imaging
      paradigm aims to estimate and map microscopic properties of tissue using a model
      that links these properties to the voxel scale MR signal. Imaging techniques of
      this type are just starting to make the transition from the technical research
      domain to wide application in biomedical studies. We focus here on the
      practicalities of both implementing such techniques and using them in
      applications. Specifically, the article summarizes the relevant aspects of brain
      microanatomy and the range of diffusion-weighted MR measurements that provide
      sensitivity to them. It then reviews the evolution of mathematical and
      computational models that relate the diffusion MR signal to brain tissue
      microstructure, as well as the expanding areas of application. Next we focus on
      practicalities of designing a working microstructure imaging technique: model
      selection, experiment design, parameter estimation, validation, and the pipeline
      of development of this class of technique. The article concludes with some future
      perspectives on opportunities in this topic and expectations on how the field
      will evolve in the short-to-medium term.

PMID- 29193414
TI  - Exploring the intervention effect moderators of a cardiovascular health promotion
      study among rural African-Americans.
AB  - OBJECTIVE: The purpose of this analysis was to examine the participant
      characteristics that served as intervention effect moderators of a cardiovascular
      health promotion intervention study. DESIGN AND SAMPLE: This exploratory study
      was a secondary analysis of data collected during a cluster randomized controlled
      trial. The participants (n = 229) of the study were African-American adults
      recruited from 12 rural churches that were randomized to intervention (n = 6) and
      control (n = 6) groups. There were 115 individual participants in the
      intervention group, and 114 in the control group. MEASURES: Cardiovascular health
      intentions, attitudes, norms, and self-efficacy for produce consumption, dietary
      fat intake, and exercise were measured to test the effect of the intervention.
      Linear mixed model was used to detect intervention effect moderators. RESULTS:
      Personal heart disease status was a moderator of intervention effects for
      intentions, norms, and self-efficacy regarding dietary fat intake and attitudes
      about produce consumption. Lacking a family heart disease history was a moderator
      for dietary fat intake self-efficacy, and age was a dietary fat norms moderator.
      CONCLUSIONS: Knowledge about the moderators that influenced intervention outcomes
      can assist public health nurses in tailoring health promotion programs for
      underserved populations that can be implemented in community settings.

PMID- 29193415
TI  - Estimating the arterial input function from dynamic contrast-enhanced MRI data
      with compensation for flow enhancement (I): Theory, method, and phantom
      experiments.
AB  - BACKGROUND: The arterial input function (AIF) represents the time-dependent
      arterial contrast agent (CA) concentration that is used in pharmacokinetic
      modeling. PURPOSE: To develop a novel method for estimating the AIF from dynamic
      contrast-enhanced (DCE-) MRI data, while compensating for flow enhancement. STUDY
      TYPE: Signal simulation and phantom measurements. PHANTOM MODEL: Time-intensity
      curves (TICs) were simulated for different numbers of excitation pulses modeling
      flow effects. A phantom experiment was performed in which a solution (without CA)
      was passed through a straight tube, at constant flow velocity. FIELD
      STRENGTH/SEQUENCE: Dynamic fast spoiled gradient echo (FSPGRs) at 3T MRI, both in
      the simulations and in the phantom experiment. TICs were generated for a duration
      of 373 seconds and sampled at intervals of 1.247 seconds (300 timepoints).
      ASSESSMENT: The proposed method first estimates the number of pulses that spins
      have received, and then uses this knowledge to accurately estimate the CA
      concentration. STATISTICAL TESTS: The difference between the median of the
      estimated number of pulses and the true value was determined, as well as the
      interquartile range (IQR) of the estimations. The estimated CA concentrations
      were evaluated in the same way. The estimated number of pulses was also used to
      calculate flow velocity. RESULTS: The difference between the median estimated and
      reference number of pulses varied from -0.005 to -1.371 (corresponding IQRs:
      0.853 and 48.377) at true values of 10 and 180 pulses, respectively. The
      difference between the median estimated CA concentration and the reference value
      varied from -0.00015 to 0.00306 mmol/L (corresponding IQRs: 0.01989 and 1.51013
      mmol/L) at true values of 0.5 and 8.0 mmol/l, respectively, at an intermediate
      value of 100 pulses. The estimated flow velocities in the phantom were within 10%
      of the reference value. DATA CONCLUSION: The proposed method accurately corrects
      the MRI signal affected by the inflow effect. LEVEL OF EVIDENCE: 1 Technical
      Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1190-1196.

PMID- 29193416
TI  - Healthcare professionals' knowledge and practice of physical activity promotion
      in cancer care: Challenges and solutions.
AB  - Limited research exists regarding healthcare professionals' knowledge and
      practice of physical activity promotion for cancer survivors in Ireland. There is
      also a lack of research identifying the barriers experienced by oncology
      professionals when promoting physical activity, or referring patients to
      community-based exercise programmes. This study aims to identify healthcare
      professionals' knowledge, barriers and practices in relation to physical activity
      promotion for cancer survivors, and to generate guidance regarding the
      optimisation of the referral process to community-based exercise programmes.
      Oncology healthcare professionals (n = 114) were invited to participate in two
      rounds of an online Delphi study. The response rates in rounds one and two were
      38% (43/114) and 70% (30/43). Most respondents acknowledged the value of physical
      activity for cancer survivors (>=86%) and agreed that discussing physical
      activity with cancer patients was part of their role (88%). However, the majority
      of recommendations provided to patients did not align with the current physical
      activity guidelines. Strategies related to four themes that could optimise the
      referral process to community-based exercise programmes achieved consensus,
      including providing education to healthcare professionals and patients regarding
      the benefits of physical activity and the logistics and quality of programmes,
      and optimising the logistics of the referral process.

PMID- 29193417
TI  - Transforming nurse-patient relationships-A qualitative study of nurse self
      disclosure in mental health care.
AB  - AIMS AND OBJECTIVES: To describe what and why nurses self-disclose to patients in
      mental health care. BACKGROUND: Self-disclosure is common, but controversial and
      difficult to delineate. Extant research suggests that self-disclosure might have
      several potentially beneficial effects on therapeutic alliance and treatment
      outcome for patients in mental health care, but results are often mixed and
      limited by definitional inconsistencies. DESIGN: Multi-site study with purposive
      sampling and source triangulation. METHOD: Qualitative descriptive study
      including data from 16 nurses taking part in participant observation, individual
      interviews and focus group interviews. RESULTS: Separate analyses resulted in
      four themes addressing the research question of what nurses self-disclose, and
      one main theme and four subthemes addressing why nurses self-disclose. The
      content of self-disclosure was captured in the four themes: Immediate family,
      Interests and activities, Life experiences and Identity. In addition, results
      showed that disclosures were common among the nurses. Self-disclosure's potential
      to transform the nurse-patient relationship, making it more open, honest, close,
      reciprocal and equal, was the overarching reason why nurses shared personal
      information. The nurses also chose to self-disclose to share existential and
      everyday sentiments, to give real-life advice, because it felt natural and
      responsive to patients' question to do so. CONCLUSION: Nurse self-disclosure is
      common and cover a variety of personal information. Nurses have several reasons
      for choosing to self-disclose, most of which are connected to improving the nurse
      patient relationship. RELEVANCE TO CLINICAL PRACTICE: Self-disclosure controversy
      can make it difficult for nurses to know whether they should share personal
      information or not. Insights into the diversity of and reasons for nurse self
      disclosure can help with deliberations on self-disclosure.

PMID- 29193418
TI  - Causes and predictors of 30-day readmission after cardiovascular implantable
      electronic devices implantation: Insights from Nationwide Readmissions Database.
AB  - INTRODUCTION: Readmissions are a burden on health care resources and have
      negative impact on patients. Cardiovascular implantable electronic devices
      (CIEDs) are frequently used in the management of rhythm disorders and advanced
      heart failure. We assessed 30-day readmissions in patients admitted for CIED
      implantation in a sample of United States patients. METHODS: Data were extracted
      from Nationwide Readmissions Database for calendar year 2013. Patients admitted
      for CIED implantation were identified using ICD-9 codes. Patients <18 years of
      age, with missing data, who died during hospitalization or discharged in December
      were excluded. Primary endpoint was all-cause 30-day readmission rate. Factors
      associated with 30-day readmissions were identified and examined using
      multivariate logistic regression. RESULTS: We identified 320,783 admissions for
      CIED implantations. After applying exclusion criteria, 290,420 patients were
      included in final analysis, out of whom 45,467 (15.7%) patients were readmitted
      within 30 days. Readmitted patients were younger and had more comorbidities.
      Septicemia (5.1%), pneumonia (3.4%), CHF (2.35%), and paroxysmal ventricular
      tachycardia (2.3%) were common primary causes of 30-day readmission. Young age,
      female gender, key comorbidities, weekend admissions, and admission to medium and
      large size hospital were independent predictors of 30-day readmissions.
      CONCLUSION: In our study, 15.7% patients were readmitted within 30 days of an
      index admission for CIED implantation. Most readmissions were due to infectious
      or cardiovascular causes. There is a need to identify patients at risk for
      readmission to improve outcomes and curb the cost of care.

PMID- 29193419
TI  - Effects of artichoke leaf extract supplementation on metabolic parameters in
      women with metabolic syndrome: Influence of TCF7L2-rs7903146 and FTO-rs9939609
      polymorphisms.
AB  - The metabolic syndrome (MetS) is a multicomponent condition with a complex
      etiology involving genetic and environmental factors. Artichoke leaf extract
      (ALE) has shown favorable effects on lipid and glucose metabolism. The present
      study aimed to investigate the effects of ALE supplementation on metabolic
      parameters in women with MetS, using a nutrigenetics approach. In this double
      blind randomized clinical trial, 50 women (aged 20-50 years) with MetS were
      randomly allocated into the two groups: "ALE group" (received 1,800 mg
      hydroalcoholic extract of artichoke as four tablets per day) and "placebo group"
      (received placebo consisted of corn starch, lactose, and avicel as four tablets
      per day) for 12 weeks. The biochemical and anthropometric parameters were
      determined before and after the intervention. The FTO-rs9939609 and the TCF7L2
      rs7903146 polymorphisms were genotyped by polymerase chain reaction-restriction
      fragment length polymorphism. In carriers of A allele of the FTO-rs9939609, ALE
      supplementation resulted in a statistically significant decrease in serum
      triglyceride level compared with placebo (-19.11% vs. 10.83%; p < .05), with no
      other significant differences between the two groups. The TCF7L2-rs7903146
      polymorphism showed no interaction with response to ALE (p > .05). These findings
      suggest that ALE supplementation may improve serum triglyceride level in A allele
      genotype of FTO-rs9939609 polymorphism in women with MetS.

PMID- 29193420
TI  - Accessory neuropathy after sternotomy: Clinico-anatomical correlation supporting
      an inflammatory cause.
AB  - Inflammatory etiologies are becoming increasingly recognized as explanations of
      some neuropathies, especially those occurring in the perioperative period.
      Although "brachial neuritis" is known to affect extraplexal nerves, accessory
      nerve palsy following median sternotomy has been attributed to stretch on the
      nerve. To better elucidate stretch as a potential cause, a cadaveric study was
      performed. Two patients who developed accessory nerve palsy following median
      sternotomy are presented to illustrate features consistent with the diagnosis of
      a perioperative inflammatory neuropathy. Five adult unembalmed cadavers underwent
      exposure of the bilateral accessory nerves in the posterior cervical triangle. A
      median sternotomy was performed and self-retaining retractors positioned. With
      the head in neutral, left rotation and right rotation, retractors were opened as
      during surgery while observing and recording any accessory nerve movements. The
      self-retaining sternal retractors were fully opened to a mean inter-blade
      distance of 13 cm. Regardless of head position, from the initial retractor click
      to maximal opening there was no gross movement of the accessory nerve on the left
      or right sides. Opening self-retaining sternal retractors does not appear to
      stretch the accessory nerve in the posterior cervical triangle. Based on our
      clinical experience and cadaveric results, we believe that inflammatory
      conditions, (i.e., idiopathic brachial plexitis) can involve the accessory nerve,
      and might be triggered by surgical procedures. Clin. Anat. 31:417-421, 2018. (c)
      2017 Wiley Periodicals, Inc.

PMID- 29193421
TI  - MicroRNA-9 promotes cell proliferation by regulating RUNX1 expression in human
      megakaryocyte development.

PMID- 29193422
TI  - The effect of short heat treatment on different properties of PET fiber using
      double beam interference microscopy.
AB  - Pluta microscope used to throw light on the effect of heat treatment time on the
      different properties of poly (ethylene terephthalate) PET fibers. PET fibers were
      annealed at times ranged from 5 to 30 min at different temperatures (150, 170,
      190, 210 degrees C) using two different processes (fast cooling and slow cooling
      processes) in air. The refractive indices, the shrinkage, orientation factor and
      crystallinity of PET fibers were determined for different annealing temperature
      during the short time treatment. The shrinkage percentage and degree of
      crystallinity increased with increasing the temperature and time of annealing.
      Microinterferograms are given for illustration.

PMID- 29193423
TI  - Assessing body awareness and autonomic reactivity: Factor structure and
      psychometric properties of the Body Perception Questionnaire-Short Form (BPQ-SF).
AB  - Body awareness and reactivity dysfunction are characteristic of a range of
      psychiatric disorders. Although the neural pathways communicating between the
      body and brain that contribute to these experiences involve the autonomic nervous
      system, few research tools for studying subjective bodily experiences have been
      informed by these neural circuits. This paper describes the factor structure,
      reliability, and convergent validity of the Body Awareness and Autonomic
      Reactivity subscales of the Body Perception Questionnaire-Short Form (BPQ-SF).
      Exploratory and confirmatory factor analyses were applied to data from three
      samples collected via the internet in Spain and the US and a college population
      in the US (combined n = 1320). Body awareness was described by a single factor.
      Autonomic reactivity reflected unique factors for organs above and below the
      diaphragm. Subscales showed strong reliability; converged with validation
      measures; and differed by age, sex, medication use, and self-reported psychiatric
      disorder. Post hoc analyses were used to create the 12-item Body Awareness Very
      Short Form. Results are discussed in relation to the distinct functions of supra-
      and sub-diaphragmatic autonomic pathways as proposed by the Polyvagal Theory and
      their potential dysfunction in psychiatric disorders.

PMID- 29193424
TI  - Oral cancer databases: A comprehensive review.
AB  - Cancer database is a systematic collection and analysis of information on various
      human cancers at genomic and molecular level that can be utilized to understand
      various steps in carcinogenesis and for therapeutic advancement in cancer field.
      Oral cancer is one of the leading causes of morbidity and mortality all over the
      world. The current research efforts in this field are aimed at cancer etiology
      and therapy. Advanced genomic technologies including microarrays, proteomics,
      transcrpitomics, and gene sequencing development have culminated in generation of
      extensive data and subjection of several genes and microRNAs that are
      distinctively expressed and this information is stored in the form of various
      databases. Extensive data from various resources have brought the need for
      collaboration and data sharing to make effective use of this new knowledge. The
      current review provides comprehensive information of various publicly accessible
      databases that contain information pertinent to oral squamous cell carcinoma
      (OSCC) and databases designed exclusively for OSCC. The databases discussed in
      this paper are Protein-Coding Gene Databases and microRNA Databases. This paper
      also describes gene overlap in various databases, which will help researchers to
      reduce redundancy and focus on only those genes, which are common to more than
      one databases. We hope such introduction will promote awareness and facilitate
      the usage of these resources in the cancer research community, and researchers
      can explore the molecular mechanisms involved in the development of cancer, which
      can help in subsequent crafting of therapeutic strategies.

PMID- 29193425
TI  - Evidence for interannual variation in genetic structure of Dungeness crab (Cancer
      magister) along the California Current System.
AB  - Using a combination of population- and individual-based analytical approaches, we
      provide a comprehensive examination of genetic connectivity of Dungeness crab
      (Cancer magister) along ~1,200 km of the California Current System (CCS). We
      sampled individuals at 33 sites in 2012 to establish a baseline of genetic
      diversity and hierarchal population genetic structure and then assessed
      interannual variability in our estimates by sampling again in 2014. Genetic
      diversity showed little variation among sites or across years. In 2012, we
      observed weak genetic differentiation among sites (FST range = -0.005-0.014)
      following a pattern of isolation by distance (IBD) and significantly high
      relatedness among individuals within nine sampling sites. In 2014, pairwise FST
      estimates were lower (FST range = -0.014-0.007), there was no spatial
      autocorrelation, and fewer sites had significant evidence of relatedness. Based
      on these findings, we propose that interannual variation in the physical
      oceanographic conditions of the CCS influences larval recruitment and thus gene
      flow, contributing to interannual variation in population genetic structure.
      Estimates of effective population size (Ne ) were large in both 2012 and 2014.
      Together, our results suggest that Dungeness crab in the CCS may constitute a
      single evolutionary population, although geographically limited dispersal results
      in an ephemeral signal of IBD. Furthermore, our findings demonstrate that
      populations of marine organisms may be susceptible to temporal changes in
      population genetic structure over short time periods; thus, interannual
      variability in population genetic measures should be considered.

PMID- 29193428
TI  - Amalgamation of Marginal Gains (AMG) as a potential system to deliver high
      quality fundamental nursing care: A qualitative analysis of interviews from high
      performance AMG sports and healthcare practitioners.
AB  - AIMS AND OBJECTIVES: To investigate the components of the Amalgamation of
      Marginal Gains (AMG) performance system to identify a set of principles that can
      be built into an innovative fundamental nursing care protocol. BACKGROUND:
      Nursing is urged to refocus on its fundamental care activities, but little
      evidence exists to guide practising nurses. Fundamental care is a combination of
      many small behaviours aimed at meeting a person's care needs. AMG is a successful
      system of performance management that focusses on small (or marginal) gains, and
      might provide a new delivery framework for fundamental nursing care. DESIGN:
      Qualitative interview study. METHODS: We undertook in-depth interviews with
      healthcare and sports professionals experienced in AMG. We analysed data using
      open coding in a framework analysis, and then interrogated the data using
      Normalisation Process Theory (NPT). We triangulated findings with AMG literature
      to develop an intervention logic model. RESULTS: We interviewed 20 AMG
      practitioners. AMG processes were as follows: focusing on many details to
      optimise performance, identification of marginal gains using different sources,
      understanding current versus optimum performance, monitoring at micro and macro
      level and strong leadership. Elements of normalisation were as follows: whole
      team belief in AMG to improve performance, a collective desire for excellence
      using evidence-based actions, whole team engagement to identify choose and
      implement changes, and individual and group responsibility for monitoring
      performance. CONCLUSIONS: We have elicited the processes described by AMG
      innovators in health care and sport and have mapped the normalisation potential
      and work required to embed such a system into nursing practice. RELEVANCE TO
      CLINICAL PRACTICE: The development of our logic model based on AMG and NPT may
      provide a practical framework for improving fundamental nursing care and is ripe
      for further development and testing in clinical trials.

PMID- 29193427
TI  - The electrical activity of the masticatory muscles in children with cleft lip and
      palate.
AB  - BACKGROUND: Information regarding masticatory muscle function in children with
      cleft lip and palate (CLP) is limited. As a consequence, research on masticatory
      muscle activity in cleft subjects is needed. AIM: To assess masticatory muscle
      activity in children surgically treated for CLP as well as identify the possible
      factors associated with this activity. DESIGN: The sample comprised 82 children
      with mixed dentition and Class I occlusions (25 children with unilateral CLP and
      57 subjects with no cleft abnormalities). A DAB-Bluetooth Instrument (Zebris
      Medical GmbH, Germany) was used to take electromyographical (EMG) recordings of
      the temporal and masseter muscles both in the mandibular rest position and during
      maximum voluntary contraction (MVC). RESULTS: Patients with clefts showed a
      significant increase in temporal muscle activity at rest compared with the
      controls. The presence of clefts and unilateral posterior crossbites are factors
      strongly associated with increased temporal muscle EMG potentials during rest
      position. CONCLUSIONS: Children with clefts have altered temporal muscle
      function. The presence of posterior crossbites affects the temporal muscle
      activity in cleft subjects. Early diagnosis and orthodontic treatment of
      malocclusions are necessary to achieve functional improvement in these patients.

PMID- 29193429
TI  - Recruiting to cohort studies in specialist healthcare services: Lessons learned
      from clinical research nurses in UK cleft services.
AB  - AIMS AND OBJECTIVES: To explore the experiences of clinical research nurses
      recruiting patients in a large specialist care-based cohort study. BACKGROUND:
      Longitudinal studies are vital to better understand the aetiology and moderators
      of health conditions. This need is especially salient for congenital conditions,
      such as cleft lip and/or palate, where establishing large, comprehensive data
      sets from birth is vital to improve understanding and to inform interventions.
      Various barriers exist in recruiting patients to large cohort studies. The role
      of clinical research nurses embedded within health settings has grown over past
      decades to facilitate data collection, yet challenges remain. DESIGN: Qualitative
      descriptive study. METHODS: Individual semi-structured interviews with 12
      clinical research nurses based in 10 National Health Service cleft services
      across the UK, recruiting to the Cleft Collective Birth Cohort Study. RESULTS: Of
      seven emergent themes, three highlighted challenges to recruiting patients,
      another three described facilitative factors, and one theme overlapped challenges
      and facilitators. Challenges included the life circumstances of potential
      participants; language barriers; and limited clinical research nurse time for
      study. Facilitative factors included integrating research into clinical practice;
      patient information shared with clinical research nurses; and support from the
      university-based research study team. The theme "Method of data collection"
      related to both challenges and facilitators. CONCLUSIONS: The qualitative data
      from clinical research nurses recruiting to a large birth cohort study provide
      helpful practical detail for specialist healthcare teams, specialist nurses,
      clinical research nurses and researchers looking to optimise recruitment and data
      collection in longitudinal studies. RELEVANCE TO CLINICAL PRACTICE: The findings
      suggest the importance of specialist clinical services and research study teams
      cooperating to embed research into everyday clinical practice, without
      compromising care. This should facilitate patients' willingness to participate in
      important research like the Cleft Collective study and provide them with a
      positive experience of research.

PMID- 29193426
TI  - Low Osteogenic Yield in Human Pluripotent Stem Cells Associates with Differential
      Neural Crest Promoter Methylation.
AB  - Human pluripotent stem cell-derived osteoblasts possess great potential for use
      in bone disorder elucidation and repair; however, while the general ability of
      human pluripotent stem cells to differentiate into osteoblasts and lay down bone
      specific matrix has been shown, previous studies lack the complete
      characterization of the process whereby such osteoblasts are derived as well as a
      comparison between the osteogenic efficiency of multiple cell lines. Here, we
      compared the osteogenic potential of two human induced pluripotent stem cell
      lines (RIV9 and RIV4) to human H9 embryonic stem cells. Generally capable of
      osteogenic differentiation, the overall osteogenic yield was lower in the RIV9
      and RIV4 lines and correlated with differential expression of osteocalcin (OCN)
      in mature cultures and PAX7 and TWIST1 during early differentiation. In the
      undifferentiated cells, the promoters of the latter two genes were differentially
      methylated potentially explaining the variation in differentiation efficiency.
      Furthermore, the expression signatures of selected neural crest and mesodermal
      genes and proteins suggested that H9 cells preferentially gave rise to neural
      crest-derived osteoblasts, whereas the osteoblasts in the RIV9 cultures were
      generated both through a mesodermal and a neural crest route although each at a
      lower rate. These data suggest that epigenetic dissimilarities between multiple
      PSC lines may lead to differences in lineage derivation and mineralization. Since
      osteoblast progenitors from one origin inadequately repair a defect in the other,
      these data underscore the importance of screening human pluripotent stem cells
      lines for the identity of the osteoprogenitors they lay down. Stem Cells
      2018;36:349-362.

PMID- 29193430
TI  - A Novel Sterically Bulky Hole Transporter to Remarkably Improve the Lifetime of
      Thermally Activated Delayed Fluorescent OLEDs at High Brightness.
AB  - For the practical application of organic light emitting devices (OLEDs) based on
      thermally activated delayed fluorescence (TADF) for large area TV and solid state
      lighting, low power consumption as well as the operation lifetime at high
      brightness over 1000 cd m-2 must be improved. Here, we have developed a novel
      hexaphenylbenzene-based sterically bulky hole-transport layer named 4DBTHPB with
      deep ionization potential of 5.8 eV and high triplet energy of 2.7 eV. By using
      4DBTHPB, we can realize a highly efficient and stable TADF OLED exhibiting
      external quantum efficiency of 21.6 % and power efficiency of 54.3 lm W-1 and
      operation lifetime at 50 % (LT50 ) of approximately 10 000 h at an initial
      luminance of 1000 cd m-2 . These performances are comparable to those of the
      state-of-the-art green phosphorescent OLEDs reported in the scientific
      literatures.

PMID- 29193431
TI  - Chemo- and Stereoselective Cross Rauhut-Currier-Type Reaction of Tri-substituted
      Alkenes Containing Trifluoromethyl Groups.
AB  - A chemoselective cross Rauhut-Currier-type reaction has been developed involving
      a tri-substituted alkene (trifluoromethyl-containing acrylonitrile derivative)
      with a di- or tri-substituted alkene to yield tetra-substituted double bonds in
      RC-type products. This approach can support the synthesis of trifluoromethylated
      tetra-substituted olefins and synthetically important, structurally complex 3
      allylic-type oxindole skeletons. The asymmetric version of this RC-type reaction
      can be realized by combining a Bronsted acid and Lewis base for bifunctional H
      bonding-tertiary amine catalysis. Subsequent transformation of multi
      functionalized RC-type product leads to pharmacologically interesting cyclohexane
      based spiro-pyrazolones bearing six contiguous chiral centers and two highly
      congested, vicinal quaternary carbon centers.

PMID- 29193432
TI  - Spatial separation of FtsZ and FtsN during cell division.
AB  - The division of Escherichia coli is mediated by a collection of some 34 different
      proteins that are recruited to the division septum and are thought to assemble
      into a macromolecular complex known as 'the divisome'. Herein, we have endeavored
      to better understand the structure of the divisome by imaging two of its core
      components; FtsZ and FtsN. Super resolution microscopy (SIM and gSTED) indicated
      that both proteins are localized in large assemblies, which are distributed
      around the division septum (i.e., forming a discontinuous ring). Although the
      rings had similar radii prior to constriction, the individual densities were
      often spatially separated circumferentially. As the cell envelope constricted,
      the discontinuous ring formed by FtsZ moved inside the discontinuous ring formed
      by FtsN. The radial and circumferential separation observed in our images
      indicates that the majority of FtsZ and FtsN molecules are organized in different
      macromolecular assemblies, rather than in a large super-complex. This conclusion
      was supported by fluorescence recovery after photobleaching measurements, which
      indicated that the dynamic behavior of the two macromolecular assemblies was also
      fundamentally different. Taken together, the data indicates that constriction of
      the cell envelope is brought about by (at least) two spatially separated
      complexes.

PMID- 29193433
TI  - Serum autoantibodies against epithelial cell adhesion molecules as disease
      biomarkers of eosinophilic esophagitis.

PMID- 29193434
TI  - Working in a storied way-Narrative-based approaches to person-centred care and
      practice development in older adult residential care settings.
AB  - AIMS AND OBJECTIVES: To evaluate the effects of the implementation of a
      methodological framework for a narrative-based approach to practice development
      and person-centred care in residential aged care settings. BACKGROUND: Care in
      long-term residential settings for older people is moving away from the
      biomedical approach and adopting a more person-centred one. Narrative can help
      shape the way care is planned and organised. The provision of person-centred care
      that is holistic and that takes account of resident's beliefs and values can be
      enhanced by incorporating narrative approaches to care within a practice
      development framework. DESIGN: The chosen methodology was participatory action
      research. METHODS: Between 2010-2014, a methodological framework of narrative
      practice was implemented in two residential care settings, comprising 37
      residents and 38 staff, using an action research approach. Three action cycles:
      (i) narrative practice and culture identification, (ii) developing narrative
      practice and (iii) working in a storied way emerged during the implementation.
      RESULTS: Key outcomes emerged in relation to the findings. These were based on
      narrative being, knowing and doing and centred around the key outcomes of (i) how
      people responded to change (narrative being), (ii) the development of shared
      understandings (narrative knowing) and (iii) intentional action (narrative
      doing). CONCLUSION: The implementation of a framework of narrative practice
      demonstrated that how people respond to change, the development of shared
      understandings and intentional action were interrelated and interlinked. It
      illustrated the importance of ensuring that practice context is taken account of
      in the implementation of action research and the importance of ensuring that
      narrative being, knowing and doing are clear and understandable for change to
      occur. RELEVANCE TO CLINICAL PRACTICE: Implementation of a narrative approach to
      care can develop new ways of working that value biography and promote the
      development of a co-constructed plan of care.

PMID- 29193435
TI  - Violent Poly-Victimization: The Longitudinal Patterns of Physical and Emotional
      Victimization Throughout Adolescence (11-17 Years).
AB  - In this study, we aimed to characterize developmental patterns of poly
      victimization in a normative sample of adolescents by applying longitudinal
      latent class analysis. Using the four most recent waves of data from the Zurich
      Project on the Social Development of Children and Youths (z-proso), we identified
      three classes, or separate groups, of youths with distinct patterns of
      victimization from age 11 to 17. The largest class represented young people who
      were least likely to be victimized in any way and at any time. The two smaller
      groups represented different types of poly-victimization-a non-parental and a
      long-term parental victimization group. Adolescents in the two groups differed
      both in the number as well as type of victimization that they experienced at
      different times. Moreover, class membership also had implications for different
      mental health outcomes.

PMID- 29193436
TI  - Editorial preface to special issue.

PMID- 29193437
TI  - Silencing of gelatinase expression delays myoblast differentiation in vitro.
AB  - Skeletal muscle growth and regeneration relies on the activation of muscle
      specific stem cells, that is, satellite cells. The activation and differentiation
      of satellite cells into myoblasts, as well as their migration, proliferation, and
      fusion of mononuclear myoblasts into a functional multi-nucleated muscle fiber,
      are associated with extracellular matrix (ECM) protein synthesis and degradation.
      The extracellular environment is dynamically adapting to the changes accompanying
      skeletal muscle growth or repair. Enzymes engaged in many biological processes
      that involve ECM remodeling are matrix metalloproteinases (MMPs). Among
      metalloproteinases crucial for skeletal muscles are two gelatinases-MMP-9 and MMP
      2. In the current study we test the effect of silencing the MMP-9 and MMP-2
      expression on the proliferation and differentiation of in vitro cultured skeletal
      muscle myoblasts. We show that downregulating gelatinase MMP-9 expression results
      in a delayed myoblast differentiation.

PMID- 29193439
TI  - Jackhammer esophagus: Assessing the balance between prepeak and postpeak
      contractile integral.
AB  - BACKGROUND: We hypothesized that symptoms in Jackhammer esophagus (JH) are
      associated with an imbalance between the prepeak and postpeak phases of
      contraction. Thus, we developed a method to distinguish the contractile integral
      components of prepeak and postpeak phase contractile activity to determine the
      contribution of each phase and their association with dysphagia. METHODS:
      Patients diagnosed with JH were enrolled and compared to controls. The first five
      intact swallows during manometry were analyzed. A single swallow was divided into
      a prepeak and postpeak phase. The contractile integral of each phase and its
      corresponding time-controlled integral were computed. All metrics were compared
      between controls and JH patients subcategorized by the impaction dysphagia
      question (IDQ) score with cut-off of 6. KEY RESULTS: Thirty eight JH patients and
      71 controls were included. Twelve JH patients had IDQ <= 6 and 26 with IDQ > 6.
      JH patients had higher contractile integral in both phases, and a higher ratio
      between postpeak to prepeak contractile integral independent of duration.
      Similarly, JH patients with an IDQ > 6 had higher contractile metrics than those
      with IDQ <= 6. There was a correlation between the IDQ score and the ratio within
      the postpeak to prepeak contractile integral (r = .375). CONCLUSIONS:
      Abnormalities in contractile integral of the postpeak phase are more significant
      in JH with higher dysphagia scores Although the total postpeak contractile
      integral was higher in symptomatic patients, this was associated with longer
      duration of postpeak activity suggesting that dysphagia patients with JH have a
      defect in the postpeak phase of peristalsis.

PMID- 29193438
TI  - Routine practice in staffed community accommodation (approved premises) in
      England and Wales: Quantitative benchmarking from the first year of a
      longitudinal study.
AB  - BACKGROUND: In England and Wales, 'approved premises' offer 24-hour staffed
      accommodation for high-risk offenders, most of whom are returning to the
      community from prison. With a move towards a standardised operating model, it is
      essential to be able to measure outcomes. AIMS: Our aim is to collate and
      evaluate 'benchmarks' for approved premises. METHODS: A cross-sectional,
      descriptive design was used to establish the impact of existing practice in all
      four approved premises in Wales. Data on well-being, life satisfaction, attitudes
      to violence and problem-solving abilities were recorded with 114 male residents
      (of 486), and attitudes to personality disorder and personal well-being/burnout
      with 30 staff (of 86), in both narrative style and according to a number of
      scales used within criminal justice and healthcare systems. Perceptions of
      environmental climate were assessed with both groups. Scores were compared with
      those from reference groups, including prisoners and secure hospital patients.
      Criminological outcomes (e.g. prison recall) were obtained for all 486 men.
      RESULTS: Scores on the scales used were broadly comparable with those in relevant
      reference groups, but some showed floor or ceiling effects. Recall rates, whether
      directly from the premises or after further onward movement, were about 42%
      overall, comparable with those reported for similar offenders elsewhere.
      CONCLUSIONS: This paper provides a short battery of measurements for use as
      benchmarks of experience and outcomes in staffed community accommodation for high
      risk men. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29193440
TI  - Mid-term outcomes and complications of total knee arthroplasty in haemophilic
      arthropathy: A review of consecutive 131 knees between 2006 and 2015 in a single
      institute.
AB  - INTRODUCTION: Although total knee arthroplasty (TKA) in haemophilic arthropathy
      can reduce severe joint pain and improve functional disability, it is technically
      demanding. AIM: To evaluate mid-term outcomes and complications of TKA in
      haemophilic arthropathy. METHODS: This study retrospectively reviewed 131
      consecutive primary TKAs in a single institute. The mean age was 41.0 years old,
      and the mean follow-up period was 6.8 years. Clinical and radiographic results
      were evaluated. Complications were categorized according to the classification
      system of the Knee Society for TKA complications. RESULTS: The average Western
      Ontario and McMaster Universities Arthritis Index (WOMAC) score improved from
      66.0 to 24.2. The average flexion contracture significantly decreased from 17.3
      degrees  to 4.7 degrees , but the average pre- and postoperative maximum flexion
      did not differ (80.9 degrees  vs 85.6 degrees , respectively). The average
      mechanical axis was varus 5.2 degrees  preoperatively and valgus 0.3 degrees 
      postoperatively. The coronal positions of the femoral and tibial components and
      the sagittal positions of these components were within +/-3 degrees  in 83.2%,
      89.3%, 63.4% and 73.3% of cases, respectively. Complications occurred in 17 knees
      (13.0%): hemarthrosis (n = 7), medial collateral ligament injury (n = 1),
      stiffness (n = 2), deep periprosthetic joint infection (PJI) (n = 3) and
      periprosthetic fracture (n = 4). CONCLUSIONS: The mid-term results of TKA in
      haemophilic arthropathy were satisfactory in pain relief, improved function and
      decreased flexion contracture. Bleeding and PJI continue to be major concerns for
      TKA in haemophilic arthropathy, and risk of periprosthetic fracture must be taken
      into account for patient education and appropriate prevention.

PMID- 29193441
TI  - Therapy for antiphospholipid miscarriages: Throwing the baby out with the
      bathwater?
AB  - PROBLEM: The association of low molecular weight heparin (LMWH) with low-dose
      aspirin (LDASA) provides the therapeutic cornerstone of obstetric anti
      phospholipid syndrome (APS). This combo approach is not effective in all
      patients, and few women still experience recurrences. METHOD OF STUDY: In an
      elegant in vitro study, Chiombori Quao and colleagues demonstrated that anti
      phospholipid antibodies (aPL) affect the functionality of endometrial endothelial
      cells interfering with angiogenesis. LMWH and LDASA, in combination or alone, did
      not display any protective activity but exacerbated aPL-mediated effects.
      RESULTS: The above data were advocated as a demonstration of the inefficacy of
      LMWH and LDASA in obstetric APS. Given the lack of thrombotic lesions in APS
      placentae, this treatment is mainly empirical. However, clinical practice clearly
      shows that LMWH and LDASA are effective in most patients. Non-responsive women
      represent a peculiar subgroup, with a high-risk aPL profile. All experimental
      models, including in vitro models of obstetric APS, display limitations that
      should be considered before translating data to patients. In particular, the use
      of a monoclonal antibody specific for Domain (D) 5 does not fit with the evidence
      that anti-D1, but not anti-D4,5, are associated with both vascular and obstetric
      APS manifestations. CONCLUSION: The association of LMWH and LDASA is the most
      effective therapeutic option for pregnant aPL-positive women. The lack of a clear
      demonstration of the pharmacological action of LMWH/LDASA should urge to further
      invtrestigate the pathophysiology of aPL-associated miscarriages.

PMID- 29193442
TI  - Visualization of the native shape of bodipy-labeled DNA in Escherichia coli by
      correlative microscopy.
AB  - The native shape and intracellular distribution of newly synthesized DNA was
      visualized by correlative (light and electron) microscopy in ice embedded whole
      cells of Escherichia coli. For that purpose, the commercially available modified
      nucleoside triphosphate named BODIPY(r) FL-14-dUTP was enzymatically incorporated
      in vivo into the genome of E. coli mutant K12 strain, which cannot synthesize
      thymine. The successful incorporation of this thymidine analogue was confirmed
      first by fluorescence microscope, where the cells were stained in the typical for
      bodipy green color. Later the preselected labeled E. coli were observed by
      Hilbert Differential Transmission Electron Microscope (HDC TEM) and the
      distribution of elemental boron (contained in bodipy) was visualized at high
      resolution by an electron spectroscopic imaging (ESI) technique. The practical
      detection limit of boron was found to be around 5 ~ 10 mmol/kg in area of 0.1
      MUm2 , which demonstrated that ESI is a suitable approach to study the
      cytochemistry and location of labeled nucleic fragments within the cytoplasmic
      chromosomal area. In addition, the fine cellular fibrous and chromosomal
      ultrastructures were revealed in situ by combing of phase-plate HDC TEM and ESI.
      The obtained results conclude that the correlation between fluorescent microscopy
      with phase-plate HDC TEM and ESI is a powerful approach to explore the structural
      and conformation dynamics of DNA replication machinery in frozen cells close to
      the living state.

PMID- 29193443
TI  - A review of sleep disturbance in children and adolescents with anxiety.
AB  - The present review examines the relations between sleep disturbance and anxiety
      in children and adolescents. The review begins with a detailed discussion of
      normative developmental trends in sleep, and the relation between sleep quality
      and emotion dysregulation in children. The extant literature on sleep disturbance
      in clinically anxious children with a focus on subjective versus objective
      measures of sleep is then summarized in detail. Finally, a review of the
      reciprocal relationship between sleep and emotion regulation is provided. The
      available research suggests that sleep disturbance is quite prevalent in children
      with anxiety disorders, although the directionality of the association between
      sleep disturbance and anxiety in children remains unclear. Despite this
      limitation, a reciprocal relationship between sleep quality and anxiety appears
      to be well established. Research using objective measures of sleep quality (e.g.
      polysomnography, sleep actigraphy, sleep bruxism) is warranted to better
      understand this relation. Further, complicating factors such as the environment
      in which sleep quality is measured, the developmental stage of participants,
      varying severity of anxiety and the timeframe during which assessment takes place
      should all be considered when examining sleep disturbance in this population.

PMID- 29193444
TI  - Morin exerts neuroprotection via attenuation of ROS induced oxidative damage and
      neuroinflammation in experimental diabetic neuropathy.
AB  - Morin, a bioflavonoid with diverse pharmacological effects against various
      diseases; in most cases morin protective effects were attributed to its
      detoxifying effect against reactive oxygen species (ROS). Diabetic neuropathy
      (DN) is a chronic, debilitating neuronal pain associated with intense generation
      of free radicals and proinflammatory cytokine accumulation in peripheral neurons.
      We investigated the pharmacological effect of morin against metabolic excess
      mediated mitochondrial ROS generation and corresponding effect on Nrf2, NF-kappaB
      pathways in Streptozotocin (STZ)-induced diabetic rats and in high glucose
      insulted Mouse neuroblastoma cell line, Neuro 2A (N2A). Animals were evaluated
      for nerve function parameters, motor and sensory nerve conduction velocities
      (MNCV and SNCV) and nerve blood flow (NBF) followed by TUNEL and immunoblot
      analysis. Mitochondrial function was evaluated by performing JC-1 and MitoSOX
      assays in high glucose (30 mM) incubated N2A cells. Diabetic animals showed
      significant impairment in MNCV, SNCV, and NBF as well as increased pain
      hypersensitivity. However, oral administration of morin at 50 and 100 mg/kg
      improved SNCV, MNCV, and NBF and reduced sensorimotor alterations (hyperalgesia
      and allodynia) in diabetic animals. Studies in N2A cells have revealed that morin
      ameliorated the high glucose-induced mitochondrial superoxide production,
      membrane depolarization, and total ROS generation. Morin effectively counteracted
      NF-kappaB-mediated neuroinflammation by reducing ROS mediated IKK activation and
      increased Nrf2-mediated antioxidant defenses in high glucose-induced N2A cells.
      The results of our study suggest that morin has exquisite role in offering
      neuroprotection in experimental DN and further clinical investigation may reward
      in finding better alternative for the management of DN. (c) 2017 BioFactors,
      44(2):109-122, 2018.

PMID- 29193445
TI  - Late-adoptions in adolescence: Can attachment and emotion regulation influence
      behaviour problems? A controlled study using a moderation approach.
AB  - A growing body of research suggests that, compared to normative adolescence,
      adoptive adolescence could be considered a specific risk condition characterized
      by more psychiatric problems, attachment insecurity, and emotional regulation
      difficulties as consequences of negative experiences in preadoption
      relationships. The current study explores (a) a moderation model of adoption
      status on the association between attachment representations (secure, dismissing,
      preoccupied, and disorganized) and behavioural problems and (b) a moderation
      model of adoption status on the association between emotion regulation processes
      (cognitive reappraisal and expressive suppression) and behavioural problems. Both
      the moderation models were controlled for verbal skills. Forty-six adopted
      adolescents and a control group of 34 nonadopted peers (12-16 years old) living
      with both their biological parents were assessed using the Friends and Family
      Interview, the Emotion Regulation Questionnaire for Children and Adolescents, the
      Child Behaviour Check List 6-18, and the verbal subtests of the Wechsler
      Intelligence Scale for Children, the latter as control measure. Results showed
      that adoption status (but not attachment) positively predicted externalizing and
      total behaviour problems, whereas attachment disorganization (but not adoption
      status) positively predicted internalizing problems in both group. Moreover, low
      cognitive reappraisal had a negative impact on externalizing problems only for
      adopted adolescents, but not for nonadopted youths. The clinical implications of
      these findings are discussed in order to enhance effective intervention with
      adopted adolescents and their parents.

PMID- 29193447
TI  - Increased severity of obstructive sleep apnea is associated with less anxiety and
      depression.
AB  - The objective was to investigate symptoms of depression and anxiety in relation
      to the presence and severity of obstructive sleep apnea (OSA) among patients
      referred with suspicion of OSA. The sample comprised 3770 consecutive patients
      with a mean age of 49.1 years; 69.7% were male. OSA was diagnosed and categorized
      based on a standard respiratory polygraphic sleep study using a type 3 portable
      monitor. Patients completed the validated Hospital Anxiety and Depression Scale
      (HADS) prior to the sleep study. In addition, they answered questions about
      whether they were currently in treatment for mental disorders and whether they
      had been diagnosed previously with depression. We adjusted for sex, age, smoking,
      alcohol consumption and obesity in the logistic regression analyses. In total,
      35.1% had apnea-hypopnea index (AHI) < 5 (no OSA), 31.9% had AHI: 5-14.9 (mild
      OSA), 17.3% had AHI: 15-29.9 (moderate OSA) and 15.7% had AHI >= 30 (severe OSA).
      The prevalence of anxiety and depressive symptoms were significantly lower with
      increased OSA severity, and also when adjusting for sex, age, smoking, alcohol
      consumption and obesity (AHI >= 15 as dependent variable). Similarly, currently
      being in treatment for mental disorders and being diagnosed previously with
      depression were both associated negatively with OSA severity, with only the
      latter remaining significant in the fully adjusted model. Furthermore, multiple
      linear regressions showed that HADS anxiety and depression total scores were
      associated negatively with AHI. In conclusion, symptoms of anxiety and depression
      were associated negatively with OSA severity in these referred patients. The
      findings remained significant also after adjusting for several relevant
      confounders.

PMID- 29193446
TI  - A distinct mechanism of senescence activation in amnion epithelial cells by
      infection, inflammation, and oxidative stress.
AB  - PROBLEM: We investigated p38MAPK activation-induced fetal membrane cell
      senescence in response to inflammation (tumour necrosis factor-alpha [TNF-alpha])
      and infection (lipopolysaccharide [LPS]), factors associated with spontaneous
      preterm birth. METHOD OF STUDY: Primary amnion epithelial cells (AECs) were
      exposed to TNF-alpha, 50 ng/mL and LPS, 100 ng/mL. Cigarette smoke extract (CSE),
      a known OS inducer, was used as positive control. AECs were cotreated with the
      antioxidant N-acetyl cysteine (NAC) and p38MAPK inhibitor SB203580 to determine
      the effect of OS and p38MAPK. Western blot analysis was performed for active
      (Phospho-p38MAPK) and total p38MAPK. Senescence was determined by flow cytometry,
      and culture supernatants were tested for IL-6 using ELISA. RESULTS: TNF-alpha,
      but not LPS, increased p38MAPK activation compared to untreated cells (P = .01).
      The number of senescent cells and senescence-associated IL-6 was higher in both
      TNF-alpha and LPS-treated cells compared to control (P = .001, P = .01,
      respectively). Antioxidant NAC inhibited p38MAPK activation by TNF-alpha. p38MAPK
      inhibitor SB203580 reduced the development of senescence and IL-6 by TNF-alpha
      and LPS. CSE treatment validated our current data. CONCLUSION: TNF-alpha caused
      OS-mediated p38MAPK induction, senescence, and IL-6 increase from AECs. LPS also
      induced senescence and IL-6 increase. Inflammatory and infectious factors may
      cause premature fetal cell senescence contributing to preterm birth
      pathophysiology.

PMID- 29193449
TI  - Characterization of glioblastoma in an orthotopic mouse model with magnetic
      resonance elastography.
AB  - Glioblastoma (GBM) is the most common primary brain tumor. It is highly malignant
      and has a correspondingly poor prognosis. Diagnosis and monitoring are mainly
      accomplished with MRI, but remain challenging in some cases. Therefore,
      complementary methods for tumor detection and characterization would be
      beneficial. Using magnetic resonance elastography (MRE), we performed a
      longitudinal study of the biomechanical properties of intracranially implanted
      GBM in mice and compared the results to histopathology. The biomechanical
      parameters of viscoelastic modulus, shear wave speed and phase angle were
      significantly lower in tumors compared with healthy brain tissue and decreased
      over time with tumor progression. Moreover, some MRE parameters revealed sub
      regions at later tumor stages, which were not easily detectable on anatomical MRI
      images. Comparison with histopathology showed that softer tumor regions contained
      necrosis and patches of viable tumor cells. In contrast, areas of densely packed
      tumor cells and blood vessels identified with histology coincided with higher
      values of viscoelastic modulus and shear wave speed. Interestingly, the phase
      angle was independent from these anatomical variations. In summary, MRE depicted
      longitudinal and morphological changes in GBM and may prove valuable for tumor
      characterization in patients.

PMID- 29193450
TI  - Clostridium butyricum exerts a neuroprotective effect in a mouse model of
      traumatic brain injury via the gut-brain axis.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a common occurrence following
      gastrointestinal dysfunction. Recently, more and more attentions are being
      focused on gut microbiota in brain and behavior. Glucagon-like peptide-1 (GLP-1)
      is considered as a mediator that links the gut-brain axis. The aim of this study
      was to explore the neuroprotective effects of Clostridium butyricum (Cb) on brain
      damage in a mouse model of TBI. METHODS: Male C57BL/6 mice were subjected to a
      model of TBI-induced by weight-drop impact head injury and were treated
      intragastrically with Cb. The cognitive deficits, brain water content, neuronal
      death, and blood-brain barrier (BBB) permeability were evaluated. The expression
      of tight junction (TJ) proteins, Bcl-2, Bax, GLP-1 receptor (GLP-1R), and
      phosphorylation of Akt (p-Akt) in the brain were also measured. Moreover, the
      intestinal barrier permeability, the expression of TJ protein and GLP-1, and IL-6
      level in the intestine were detected. RESULTS: Cb treatment significantly
      improved neurological dysfunction, brain edema, neurodegeneration, and BBB
      impairment. Meanwhile, Cb treatment also significantly increased the expression
      of TJ proteins (occludin and zonula occluden-1), p-Akt and Bcl-2, but decreased
      expression of Bax. Moreover, Cb treatment exhibited more prominent effects on
      decreasing the levels of plasma d-lactate and colonic IL-6, upregulating
      expression of Occludin, and protecting intestinal barrier integrity. Furthermore,
      Cb-treated mice showed increased the secretion of intestinal GLP-1 and
      upregulated expression of cerebral GLP-1R. CONCLUSIONS: Our findings demonstrated
      the neuroprotective effect of Cb in TBI mice and the involved mechanisms were
      partially attributed to the elevating GLP-1 secretion through the gut-brain axis.

PMID- 29193448
TI  - Increased CEST specificity for amide and fast-exchanging amine protons using
      exchange-dependent relaxation rate.
AB  - Chemical exchange saturation transfer (CEST) imaging of amides at 3.5 ppm and
      fast-exchanging amines at 3 ppm provides a unique means to enhance the
      sensitivity of detection of, for example, proteins/peptides and
      neurotransmitters, respectively, and hence can provide important information on
      molecular composition. However, despite the high sensitivity relative to
      conventional magnetic resonance spectroscopy (MRS), in practice, CEST often has
      relatively poor specificity. For example, CEST signals are typically influenced
      by several confounding effects, including direct water saturation (DS), semi
      solid non-specific magnetization transfer (MT), the influence of water relaxation
      times (T1w ) and nearby overlapping CEST signals. Although several editing
      techniques have been developed to increase the specificity by removing DS, semi
      solid MT and T1w influences, it is still challenging to remove overlapping CEST
      signals from different exchanging sites. For instance, the amide proton transfer
      (APT) signal could be contaminated by CEST effects from fast-exchanging amines at
      3 ppm and intermediate-exchanging amines at 2 ppm. The current work applies an
      exchange-dependent relaxation rate (Rex ) to address this problem. Simulations
      demonstrate that: (1) slowly exchanging amides and fast-exchanging amines have
      distinct dependences on irradiation powers; and (2) Rex serves as a resonance
      frequency high-pass filter to selectively reduce CEST signals with resonance
      frequencies closer to water. These characteristics of Rex provide a means to
      isolate the APT signal from amines. In addition, previous studies have shown that
      CEST signals from fast-exchanging amines have no distinct features around their
      resonance frequencies. However, Rex gives Lorentzian lineshapes centered at their
      resonance frequencies for fast-exchanging amines and thus can significantly
      increase the specificity of CEST imaging for amides and fast-exchanging amines.

PMID- 29193452
TI  - Finnish cytotechnologists' views on the competencies of newly graduated
      biomedical scientists in clinical cytology.
AB  - OBJECTIVE: This study asked 40 cytotechnologists for their views on the
      competencies of newly graduated biomedical scientists in clinical cytology during
      the national conference of the Finnish Association of Cytotechnologists in
      November 2015. METHODS: The questionnaire mainly consisted of statements that
      were scored on a five-point Likert-scale, where 1 was not important and 5 was
      very important. It covered five sections of clinical cytology: sampling and
      techniques, gynaecological screening, non-gynaecological screening, safety and
      quality management, and miscellaneous. RESULTS: Of the 40 delegates approached to
      complete the questionnaire, 37 (92.5%) agreed. Respondents felt that important
      sampling and technique competencies were specimen fixation, with a mean score of
      4.9 out of 5.0, types of specimens (4.7), Papanicolaou smear collection (4.7),
      Papanicolaou smear request information (4.7) and evaluation of specimen
      sufficiency (4.6). Less important competencies were examining FNAs (2.0) and
      nasopharyngeal specimens (2.2). The respondents had many expectations about how
      education in cytology could be developed, for example more theoretical lessons,
      more practice in microscope use, and consistent criteria for training and
      cooperation between cytology laboratories and universities of applied sciences.
      CONCLUSIONS: The cytotechnologists who took part in our survey expected newly
      graduated biomedical scientists to have basic competencies in cytology. These
      were sampling and techniques, laboratory safety and quality management, specimen
      adequacy and identifying normal cells taken during gynaecological screening. They
      were also keen to develop education in cytology.

PMID- 29193453
TI  - Cross-cultural adaptation and validation of the Chinese Comfort, Afford, Respect,
      and Expect scale of caring nurse-patient interaction competence.
AB  - AIMS AND OBJECTIVES: To investigate the construct validity and reliability of the
      Chinese Comfort, Afford, Respect, and Expect scale, which can be used to
      determine clinical nurses' competence. The results can also serve to promote
      nursing competence and improve patient satisfaction. BACKGROUND: Nurse-patient
      interaction is critical for improving nursing care quality. However, to date, no
      relevant validated instrument has been proposed for assessing caring nurse
      patient interaction competence in clinical practice. This study adapted and
      validated the Chinese version of the caring nurse-patient interaction scale.
      DESIGN: A cross-cultural adaptation and validation study. METHODS: A psychometric
      analysis of the four major constructs of the Chinese Comfort, Afford, Respect,
      and Expect scale was conducted on a sample of 356 nurses from a medical centre in
      China. Item analysis and exploratory factor analysis were adopted to extract the
      main components, both the internal consistency and correlation coefficients were
      used to examine reliability and a confirmatory factor analysis was adopted to
      verify the construct validity. RESULTS: The goodness-of-fit results of the model
      were strong. The standardised factor loadings of the Chinese Comfort, Afford,
      Respect, and Expect scale ranged from 0.73-0.95, indicating that the validity and
      reliability of this instrument were favourable. Moreover, the 12 extracted items
      explained 95.9% of the measured content of the Chinese Comfort, Afford, Respect,
      and Expect scale. CONCLUSIONS: The results serve as empirical evidence regarding
      the validity and reliability of the Chinese Comfort, Afford, Respect, and Expect
      scale. RELEVANCE TO CLINICAL PRACTICE: Hospital nurses increasingly demand help
      from patients and their family members in identifying health problems and
      assisting with medical decision-making. Therefore, enhancing nurses' competence
      in nurse-patient interactions is crucial for nursing and hospital managers to
      improve nursing care quality. The Chinese caring nurse-patient interaction scale
      can serve as an effective tool for nursing and hospital managers to evaluate the
      caring nurse-patient interaction confidence of nurses and improve inpatient
      satisfaction and quality of care.

PMID- 29193451
TI  - Retinoic Acid-Signaling Regulates the Proliferative and Neurogenic Capacity of
      Muller Glia-Derived Progenitor Cells in the Avian Retina.
AB  - In the retina, Muller glia have the potential to become progenitor cells with the
      ability to proliferate and regenerate neurons. However, the ability of Muller
      glia-derived progenitor cells (MGPCs) to proliferate and produce neurons is
      limited in higher vertebrates. Using the chick model system, we investigate how
      retinoic acid (RA)-signaling influences the proliferation and the formation of
      MGPCs. We observed an upregulation of cellular RA binding proteins (CRABP) in the
      Muller glia of damaged retinas where the formation of MGPCs is known to occur.
      Activation of RA-signaling was stimulated, whereas inhibition suppressed the
      proliferation of MGPCs in damaged retinas and in fibroblast growth factor 2
      treated undamaged retinas. Furthermore, inhibition of RA-degradation stimulated
      the proliferation of MGPCs. Levels of Pax6, Klf4, and cFos were upregulated in
      MGPCs by RA agonists and downregulated in MGPCs by RA antagonists. Activation of
      RA-signaling following MGPC proliferation increased the percentage of progeny
      that differentiated as neurons. Similarly, the combination of RA and insulin-like
      growth factor 1 (IGF1) significantly increased neurogenesis from retinal
      progenitors in the circumferential marginal zone (CMZ). In summary, RA-signaling
      stimulates the formation of proliferating MGPCs and enhances the neurogenic
      potential of MGPCs and stem cells in the CMZ. Stem Cells 2018;36:392-405.

PMID- 29193454
TI  - Amniotic fluid pentraxins: Potential early markers for identifying intra-amniotic
      inflammatory complications in preterm pre-labor rupture of membranes.
AB  - In this study, pentraxin 3 (PTX3), C-reactive protein (CRP), and serum amyloid P
      component (SAP) concentrations in the amniotic fluid of women with preterm pre
      labor rupture of membranes (PPROM) were evaluated based on evidence of microbial
      invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and
      microbial-associated IAI. A total of 149 women with PPROM were included in this
      study. Amniotic fluid samples were obtained by transabdominal amniocentesis.
      Amniotic fluid PTX3, SAP, and CRP concentrations were assessed using enzyme
      linked immunosorbent assay. PTX3 and CRP concentrations were higher in women with
      MIAC, IAI, and microbial-associated IAI than in women without these conditions.
      SAP concentrations were only higher in the presence of IAI and microbial
      associated IAI. Amniotic fluid PTX3 concentrations of 11 ng/mL were found to be
      the best value for identifying the presence of microbial-associated IAI and IAI
      in women with PPROM. To conclude, amniotic fluid pentraxins are involved in intra
      amniotic inflammatory responses in pregnancies complicated by PPROM.

PMID- 29193455
TI  - The Parkinson's Disease Composite Scale: results of the first validation study.
AB  - BACKGROUND AND PURPOSE: The aim was to validate the Parkinson's Disease Composite
      Scale (PDCS). METHODS: The study included 194 Parkinson's disease (PD) patients
      in five countries. Investigators completed the following scales: PDCS, the
      Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS),
      Parkinson's Disease Sleep Scale Version 2, Montreal Cognitive Assessment, the
      Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's Disease and the
      Clinical Impression of Severity Index for PD (CISI-PD). For test-retest analysis,
      a second administration of the PDCS was carried out in 61 stable patients (as per
      the CISI-PD) in 7-14 days after the first evaluation. The PDCS is a novel scale
      for PD with a total of 17 items divided into four domains: motor, non-motor,
      treatment complications and disability. RESULTS: Parkinson's Disease Composite
      Scale mean and median values were close. Skewness values were into the criterion
      limits (-1 to +1). The complete range of scores was covered for 14 of the 17
      items (83.4%). A floor effect of 25.26% and 28.25% was observed in the
      complications and disability level dimensions due to the proportion of patients
      free of these difficulties. No relevant floor or ceiling effect was observed for
      the PDCS total score (1.03% and 0.52%, respectively). The stability of the scale
      appeared excellent with most items meeting weighted kappa and intraclass
      correlation coefficient values >0.80. The convergent validity of the PDCS with
      corresponding scores of the MDS-UPDRS showed high correlation values (rS  >=
      0.60). The internal validity was into acceptable limits, with the majority of
      values higher than the minimal 0.30 threshold. The standard error of measurement
      suggested a satisfactory precision (SEM 3.81, <30% of the PDCS total score
      standard deviation). CONCLUSION: The PDCS appears to be a feasible, acceptable,
      reproducible and valid scale.

PMID- 29193457
TI  - Factors associated with adoption of coping strategies among Chinese patients with
      heart failure in ethnic minority regions.
AB  - AIMS AND OBJECTIVES: To examine the coping strategies in patients with heart
      failure (HF) in the ethnic minority regions of China and to explore the factors
      affecting the adoption of coping strategies. BACKGROUND: Effective coping with
      illness is an important element that influences the adaptation and increases the
      patient quality of life. Although different factors have been proposed to be
      determinants of coping strategy, findings are inconclusive, especially when it
      comes to the cultural background. DESIGN: A cross-sectional study was performed.
      METHODS: A total of 360 HF patients in four districts of Xinjiang were enrolled.
      All participants completed the Medical Coping Modes Questionnaire, the Minnesota
      Living with HF Questionnaire and self-management Questionnaire. RESULTS: Heart
      failure patients had lower scores in confrontation and higher scores in avoidance
      and acceptance resignation than patients in the Chinese norm. The multiple
      regression analysis revealed several factors that indicate confrontation coping
      including symptom management, employment status and psychological and social
      management, whereas religion (R2), disease duration, employment status and
      payment system (P2) were identified as indicators of avoidance coping. In
      addition, ethnicity (E1), disease duration and employment status were indicators
      of acceptance resignation coping. CONCLUSIONS: Our findings from this study
      suggest that HF patients in the ethnic minority regions may use less
      confrontation coping and more avoidance and acceptance resignation coping than
      patients in the Chinese norm. Moreover, the cultural background, duration of
      disease, quality of life and self-management play important roles in the
      selection of HF coping strategy. RELEVANCE TO CLINICAL PRACTICE: The disparities
      of racial/ethnic exist in coping strategy. Healthcare providers are required to
      better understand the role of religion in the coping process and how it
      contributes to the selection of coping strategies.

PMID- 29193458
TI  - High prevalence of Clostridium difficile on retail root vegetables, Western
      Australia.
AB  - AIMS: The incidence of community-associated Clostridium difficile infection (CA
      CDI) in Australia has increased since mid-2011. With reports of clinically
      important C. difficile strains being isolated from retail foods in Europe and
      North America, a foodborne source of C. difficile in cases of CA-CDI is a
      possibility. This study represents the first to investigate the prevalence and
      genotypes of C. difficile in Australian retail vegetables. METHODS AND RESULTS: A
      total of 300 root vegetables grown in Western Australia (WA) were collected from
      retail stores and farmers' markets. Three vegetables of the same kind bought from
      the same store/market were treated as one sample. Selective enrichment culture,
      toxin profiling and PCR ribotyping were performed. Clostridium difficile was
      isolated from 30% (30/100) of pooled vegetable samples, 55.6% of organic
      potatoes, 50% of nonorganic potatoes, 22.2% of organic beetroots, 5.6% of organic
      onions and 5.3% of organic carrots. Over half (51.2%, 22/43) the isolates were
      toxigenic. Many of the ribotypes of C. difficile isolated were common among human
      and Australian animals. CONCLUSIONS: Clostridium difficile could be found
      commonly on retail root vegetables of WA. This may be potential sources for CA
      CDI. SIGNIFICANCE AND IMPACT OF THE STUDY: This study enhances knowledge of
      possible sources of C. difficile in the Australian community, outside the
      hospital setting.

PMID- 29193459
TI  - Neuropeptide CART prevents memory loss attributed to withdrawal of nicotine
      following chronic treatment in mice.
AB  - Although chronic nicotine administration does not affect memory, its withdrawal
      causes massive cognitive deficits. The underlying mechanisms, however, have not
      been understood. We test the role of cocaine- and amphetamine-regulated
      transcript peptide (CART), a neuropeptide known for its procognitive properties,
      in this process. The mice on chronic nicotine treatment/withdrawal were subjected
      to novel object recognition task. The capability of the animal to discriminate
      between the novel and familiar objects was tested and represented as
      discrimination index (DI); reduction in the index suggested amnesia. Nicotine for
      49 days had no effect on DI, but 8-hour withdrawal caused a significant
      reduction, followed by full recovery at 24-hour withdrawal timepoint. Bilateral
      CART infusion in dorsal hippocampus rescued deficits in DI at 8-hours, whereas
      CART-antibody infusion into the dorsal hippocampus attenuated the recovery at 24
      hours. Commensurate changes were observed in the CART as well as CART mRNA
      profiles in the hippocampus. CART mRNA expression and the peptide
      immunoreactivity did not change significantly following chronic nicotine
      treatment. However, there was a significant reduction at 8-hour withdrawal,
      followed by a drastic increase in CART immunoreactivity as well as CART mRNA at
      24-hour withdrawal, compared with 8-hour withdrawal. Distinct alpha7-nicotinic
      receptor immunoreactivity was detected on the hippocampal CART neurons,
      suggesting cholinergic inputs. An increase in the synaptophysin immunoreactive
      elements around CART cells in the dentate gyrus, cornu ammonis 3 and subiculum at
      24-hour post-withdrawal timepoint suggested neuronal plasticity. CART circuit
      dynamics in the hippocampus seems to modulate short-term memory associated with
      nicotine withdrawal.

PMID- 29193460
TI  - Corticospinal tract diffusion properties and robotic visually guided reaching in
      children with hemiparetic cerebral palsy.
AB  - Perinatal stroke is the leading cause of hemiparetic cerebral palsy (CP),
      resulting in life-long disability. In this study, we examined the relationship
      between robotic upper extremity motor impairment and corticospinal tract (CST)
      diffusion properties. Thirty-three children with unilateral perinatal ischemic
      stroke (17 arterial, 16 venous) and hemiparesis were recruited from a population
      based research cohort. Bilateral CSTs were defined using diffusion tensor imaging
      (DTI) and four diffusion metrics were quantified: fractional anisotropy (FA),
      mean (MD), radial (RD), and axial (AD) diffusivities. Participants completed a
      visually guided reaching task using the KINARM robot to define 10 movement
      parameters including movement time and maximum speed. Twenty-six typically
      developing children underwent the same evaluations. Partial correlations assessed
      the relationship between robotic reaching and CST diffusion parameters. All
      diffusion properties of the lesioned CST differed from controls in the arterial
      group, whereas only FA was reduced in the venous group. Non-lesioned CST
      diffusion measures were similar between stroke groups and controls. Both stroke
      groups demonstrated impaired reaching performance. Multiple reaching parameters
      of the affected limb correlated with lesioned CST diffusion properties. Lower FA
      and higher MD were associated with greater movement time. Few correlations were
      observed between non-lesioned CST diffusion and unaffected limb function though
      FA was associated with reaction time (R = -0.39, p < .01). Diffusion properties
      of the lesioned CST are altered after perinatal stroke, the degree of which
      correlates with specific elements of visually guided reaching performance,
      suggesting specific relevance of CST structural connectivity to clinical motor
      function in hemiparetic children.

PMID- 29193461
TI  - Site-specific gene expression analysis from archived human intestine samples
      combining laser-capture microdissection and multiplexed color-coded probes.
AB  - BACKGROUND: Alterations of site-specific gene expression profiles in disease
      relevant networks within the different layers of the intestinal wall may
      contribute to the onset and clinical course of gastrointestinal disorders. To
      date, no systematic analysis has assessed and compared sub-regional gene
      expression patterns in all distinct layers of the gut using fresh frozen human
      samples. Our aim was to establish an optimized protocol for site-specific RNA
      isolation in order to achieve maximum RNA quality and amount for subsequent gene
      expression analysis combining laser-capture microdissection (LCM) with a probe
      based technology, the NanoString nCounter Analysis system. METHODS: Four full
      thickness colon samples from patients who underwent surgery due to pathological
      conditions were processed and separated into epithelium, lamina propria,
      myenteric plexus, submucosa, and tunica muscularis by LCM. Site-specific marker
      expression by nCounter technology was performed on total RNA from each sub
      region, respectively. KEY RESULTS: Collecting ~10 mm2 (~100 000-250 000 cells) of
      tissue from the epithelial layer, lamina propria, and myenteric plexus provided
      sufficient amounts of RNA of appropriate quality for subsequent analyses. In
      contrast, ~40 mm2 (~250 000-650 000 cells) of tissue were dissected from the less
      cell-rich submucosal and tunica muscularis layer. nCounter analysis revealed a
      site-specific expression pattern of marker genes in the different layers of the
      colonic wall which were highly correlating (r > .9). CONCLUSIONS AND INFERENCES:
      LCM in combination with nCounter expression analysis enables site-specific,
      sensitive, reliable detection, and quantification of mRNA from histologically
      heterogeneous tissues.

PMID- 29193462
TI  - Contribution of cardiac and extra-cardiac disease burden to risk of
      cardiovascular outcomes varies by ejection fraction in heart failure.
AB  - AIMS: Patients with heart failure (HF) often have multiple co-morbidities that
      contribute to the risk of adverse cardiovascular (CV) and non-CV outcomes. We
      assessed the relative contribution of cardiac and extra-cardiac disease burden
      and demographic factors to CV outcomes in HF patients with reduced (HFrEF) or
      preserved (HFpEF) left ventricular ejection fraction (LVEF). METHODS AND RESULTS:
      We utilized data from the CHARM trial, which enrolled HF patients across the
      ejection fraction spectrum. We decomposed the previously validated MAGGIC risk
      score into cardiac (LVEF, New York Heart Association class, systolic blood
      pressure, time since HF diagnosis, HF medication use), extra-cardiac (body mass
      index, creatinine, diabetes mellitus, chronic obstructive pulmonary disease,
      smoker), and demographic (age, gender) categories, and calculated subscores for
      each patient representing the burden of each component. Cox proportional hazards
      models were used to estimate the population attributable risk (PAR) associated
      with each component to the outcomes of death, CV death, HF, myocardial
      infarction, and stroke relative to patients with the lowest risk score. PARs for
      each component were depicted across the spectrum of LVEF. in 2675 chronic HF
      patients from North America [HFrEF (LVEF <=40%): n = 1589, HFpEF (LVEF >40%): n =
      1086] with data available for calculation of the MAGGIC score, the highest risk
      of death and CV death was attributed to cardiac burden. This was especially
      evident in HFrEF patients (PAR: 76% cardiac disease vs. 58% extra-cardiac
      disease, P < 0.05). Conversely, in HFpEF patients, extra-cardiac burden accounted
      for a greater proportion of risk for death than cardiac burden (PAR: 15% cardiac
      disease vs. 49% extra-cardiac disease, P < 0.05). For HF hospitalization, the
      contribution of both cardiac and extra-cardiac burden was comparable in HFpEF
      patients (PAR: 42% cardiac disease vs. 53% extra-cardiac disease, P = NS). In
      addition, demographic burden was especially high in HFpEF patients, with 62% of
      deaths attributable to demographic characteristics. CONCLUSION: In North American
      HF patients enrolled in the CHARM trials, the relative contribution of cardiac
      and extra-cardiac disease burden to CV outcomes and death differed depending on
      LVEF. The high risk of events attributable to non-cardiac disease burden may help
      explain why cardiac disease-modifying medication proven to be efficacious in
      HFrEF patients has not proven beneficial in HFpEF.

PMID- 29193466
TI  - Asthma, urticaria and less rare than expected FPIES.

PMID- 29193463
TI  - Placental exosomes: A proxy to understand pregnancy complications.
AB  - Exosomes (30- to 150-nm particles), originating from multivesicular bodies by the
      invagination of the endosomal membrane, are communication channels between cells.
      Exosomes are released by various cell types and cargo proteins, lipids, and
      nucleic acids reflecting the physiologic status of their cells of origin and
      cause functional changes in recipient cells, which are likely dependent on their
      quantity and/or cargo contents. Recently, placental exosomes, produced by various
      placental cell types, have been isolated from maternal blood using the placental
      protein-specific marker, placental alkaline phosphatase (PLAP). PLAP-positive
      exosomes are seen in maternal blood as early as the first trimester of pregnancy
      and increase as gestation progresses, with maximum numbers seen at term. Although
      the functional relevance of placental exosomes is still under investigation,
      several studies have linked placental exosomes changes (quantity and cargo)
      reflecting placental dysfunctions associated with adverse pregnancy events. As
      placental exosomes can be isolated from maternal blood, they are liquid biopsies
      reflecting placental functions. Hence, they are useful as biomarkers of placental
      functions and dysfunctions obtainable through non-invasive approaches. This
      review summarizes the biogenesis, release, and functions of exosomes and
      specifically expounds the role of placental-specific exosomes and their
      significance associated with pregnancy complications.

PMID- 29193464
TI  - Functional connectivity in dementia with Lewy bodies: A within- and between
      network analysis.
AB  - Dementia with Lewy bodies (DLB) is a common form of dementia and is characterized
      by cognitive fluctuations, visual hallucinations, and Parkinsonism. The
      phenotypic expression of the disease may, in part, relate to alterations in
      functional connectivity within and between brain networks. This resting-state
      study sought to clarify this in DLB, how networks differed from Alzheimer's
      disease (AD), and whether they were related to clinical symptoms in DLB. Resting
      state networks were estimated using independent component analysis. We
      investigated functional connectivity changes in 31 DLB patients compared to 31
      healthy controls and a disease comparator group of 29 AD patients using dual
      regression and FSLNets. Within-network connectivity was generally decreased in
      DLB compared to controls, mainly in motor, temporal, and frontal networks.
      Between-network connectivity was mainly intact; only the connection between a
      frontal and a temporal network showed increased connectivity in DLB. Differences
      between AD and DLB were subtle and we did not find any significant correlations
      with the severity of clinical symptoms in DLB. This study emphasizes the
      importance of reduced connectivity within motor, frontal, and temporal networks
      in DLB with relative sparing of the default mode network. The lack of significant
      correlations between connectivity measures and clinical scores indicates that the
      observed reduced connectivity within these networks might be related to the
      presence, but not to the severity of motor and cognitive impairment in DLB
      patients. Furthermore, our results suggest that AD and DLB may show more
      similarities than differences in patients with mild disease.

PMID- 29193467
TI  - Highly Selective Ruthenium-Catalyzed Direct Oxygenation of Amines to Amides.
AB  - Reports on aerobic oxidation of amines to amides are rare, and those reported
      suffer from several limitations like poor yield or selectivity and make use of
      pure oxygen under elevated pressure. Herein, we report a practical and an
      efficient ruthenium-catalyzed synthetic protocol that enables selective oxidation
      of a broad range of primary aliphatic, heterocyclic and benzylic amines to their
      corresponding amides, using readily available reagents and ambient air as the
      sole oxidant. Secondary amines instead, yield benzamides selectively as the sole
      product. Mechanistic investigations reveal intermediacy of nitriles, which
      undergo hydration to afford amide as the final product.

PMID- 29193468
TI  - Perceptions and experiences of nutritional care following the overwhelming
      experience of lower extremity amputation: A qualitative study.
AB  - INTRODUCTION: Good nutritional care of people following major lower extremity
      amputation is essential as poor nutritional status can lead to delayed wound
      healing. Working with patients to identify their perspectives on food, views on
      nutritional care and the need for dietary counselling enables the development of
      optimised nutritional care. AIMS AND OBJECTIVES: To explore hospital patients'
      perspectives on food, dietary counselling and their experiences of nutritional
      care following lower extremity amputation. DESIGN: A qualitative, explorative
      study design was employed. METHOD: An inductive content analysis of semi
      structured interviews with a purposive sample of 17 people over 50 years of age,
      who had recently undergone major lower extremity amputation, was undertaken. The
      study was reported according to the consolidated criteria for reporting
      qualitative research guideline. FINDINGS: Three themes emerged: responsible for
      own dietary intake, diet based on preferences and experiences with dietary
      counselling and feeling overwhelmed. The participants expressed motivation to
      ensure their nutritional needs were met but described feeling emotionally
      overwhelmed by the experience of amputation. They appeared not to expect nursing
      staff to focus on nutritional issues as they expressed belief that they
      themselves were solely responsible for their dietary intake. They described being
      motivated to receive nutritional counselling but indicated advice should be
      compatible with their lifestyle and eating habits. CONCLUSION: Lower extremity
      amputation can be an overwhelming experience which affects nutritional intake.
      People appear to consider themselves responsible for their nutritional care and
      describe not experiencing or expecting nursing staff to engage in this aspect of
      care. Dietary counselling by nurses who respect and incorporate patient
      preferences and experiences following amputation has the potential to enhance
      nutritional care. RELEVANCE TO CLINICAL PRACTICE: This study illustrates that
      nurses caring for people who undergo lower extremity amputation need to recognise
      that nutritional care is an essential component of nursing and should focus on
      working in partnership with the patient.

PMID- 29193469
TI  - Estimating the arterial input function from dynamic contrast-enhanced MRI data
      with compensation for flow enhancement (II): Applications in spine diagnostics
      and assessment of crohn's disease.
AB  - BACKGROUND: Pharmacokinetic (PK) models can describe microvascular density and
      integrity. An essential component of PK models is the arterial input function
      (AIF) representing the time-dependent concentration of contrast agent (CA) in the
      blood plasma supplied to a tissue. PURPOSE/HYPOTHESIS: To evaluate a novel method
      for subject-specific AIF estimation that takes inflow effects into account. STUDY
      TYPE: Retrospective study. SUBJECTS: Thirteen clinical patients referred for
      spine-related complaints; 21 patients from a study into luminal Crohn's disease
      with known Crohn's Disease Endoscopic Index of Severity (CDEIS). FIELD
      STRENGTH/SEQUENCE: Dynamic fast spoiled gradient echo (FSPGR) at 3T. ASSESSMENT:
      A population-averaged AIF, AIFs derived from distally placed regions of interest
      (ROIs), and the new AIF method were applied. Tofts' PK model parameters
      (including vp and Ktrans ) obtained with the three AIFs were compared. In the
      Crohn's patients Ktrans was correlated to CDEIS. STATISTICAL TESTS: The median
      values of the PK model parameters from the three methods were compared using a
      Mann-Whitney U-test. The associated variances were statistically assessed by the
      Brown-Forsythe test. Spearman's rank correlation coefficient was computed to test
      the correlation of Ktrans to CDEIS. RESULTS: The median vp was significantly
      larger when using the distal ROI approach, compared to the two other methods (P <
      0.05 for both comparisons, in both applications). Also, the variances in vp were
      significantly larger with the ROI approach (P < 0.05 for all comparisons). In the
      Crohn's disease study, the estimated Ktrans parameter correlated better with the
      CDEIS (r = 0.733, P < 0.001) when the proposed AIF was used, compared to AIFs
      from the distal ROI method (r = 0.429, P = 0.067) or the population-averaged AIF
      (r = 0.567, P = 0.011). DATA CONCLUSION: The proposed method yielded realistic PK
      model parameters and improved the correlation of the Ktrans parameter with CDEIS,
      compared to existing approaches. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 1
      J. Magn. Reson. Imaging 2018;47:1197-1204.

PMID- 29193470
TI  - Response to "Prognostic value of pathologic grade for patients with oral squamous
      cell carcinoma: Methodological issues".

PMID- 29193471
TI  - Effect of quantitative assessment-based nursing intervention on the bowel
      function and life quality of patients with neurogenic bowel dysfunction after
      spinal cord injury.
AB  - AIMS AND OBJECTIVES: To study the effect of quantitative assessment-based nursing
      intervention on the bowel function and life quality of patients with neurogenic
      bowel dysfunction after spinal cord injury. BACKGROUND: Neurogenic bowel
      dysfunction after spinal cord injury was clinically manifested by abdominal
      distension, intractable constipation, prolonged defecation and faecal
      incontinence, which seriously affected the normal life of patients. Traditional
      ways of nursing for these patients focused on basic care, but lacked sufficient
      recognition of disease severity and individual needs. DESIGN: One hundred and
      eighty-four patients with neurogenic bowel dysfunction after spinal cord injury
      were randomly allocated into observation group (n = 92) and control group (n =
      92). METHODS: The patients in the control group were given regular nursing, and
      the patients in the observation group were given quantitative assessment-based
      nursing intervention. Recovery of bowel function, quality of life and
      satisfaction were compared between the two groups. RESULTS: Scores for bowel
      function including bloating, constipation, prolonged defecation, defecation drug
      dependence and faecal incontinence in the observation group were significantly
      lower than those in the control group (p < .05). The scores for the quality of
      life including physical function, general health, social functioning, role
      motional, mental health in the observation group were significantly higher than
      those in the control group (p < .001). Finally, the satisfaction rate in the
      observation group was 95.56%, which was significantly higher than that in the
      control group (83.7%) (p < .01). CONCLUSION: We concluded that quantitative
      assessment-based nursing intervention contributed to recovery of bowel function
      and improvement of life quality and satisfaction. RELEVANCE TO CLINICAL PRACTICE:
      Our finding can increase the rational allocation of nurse-patient ratio and
      provide personalised nursing for severe patients to reduce complications and
      promote the rehabilitation of the disease. Our findings can also serve as a
      reference for other countries to develop the nurse practitioner role.

PMID- 29193472
TI  - Intellectual disability is a risk factor for delayed emergence from total
      intravenous anaesthesia.
AB  - BACKGROUND: Previous studies have suggested that ID influences the depth of
      general anaesthesia (GA) and delays emergence from GA. In this retrospective
      cohort study, we investigated whether ID affects the time taken to emerge from
      GA. METHODS: We selected dental patients who underwent GA at the Department of
      Dental Anaesthesiology, Okayama University Hospital, using predefined inclusion
      and exclusion criteria, before dividing the selected participants into ID and non
      ID (control) groups. Relevant data were collected from electronic anaesthesia
      records. Emergence time, the time from the discontinuation of propofol and
      remifentanil to tracheal extubation, was recorded for each patient. We compared
      the data of the ID group and control group. The association between ID and the
      emergence time was tested for statistical significance. Multivariate linear
      regression analysis was used to control for confounders. RESULTS: A total of 97
      cases (control = 50, ID = 47) were included in the study. The emergence time was
      significantly longer in the ID group (ID group: 15.8 +/- 6.6 min, control group:
      10.8 +/- 3.6 min). The ID group included more men and lower propofol and
      remifentanil infusion rates. The treatment time was longer, and the mean
      bispectral index was lower in the ID group. Sevoflurane inhalation was used only
      for anaesthesia induction in the ID group. In the multivariate linear regression
      analysis, ID was found to be significantly associated with a longer emergence
      time. CONCLUSION: Our results suggest that ID is associated with a longer
      emergence time from GA.

PMID- 29193473
TI  - Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a
      retrospective study.
AB  - BACKGROUND AND PURPOSE: The aim was to describe the clinical, radiological and
      pathological features of an autoimmune glial fibrillary acidic protein (GFAP)
      astrocytopathy. METHODS: Data from 19 patients with positive GFAP-immunoglobulin
      G in cerebrospinal fluid (CSF) were retrospectively analyzed. RESULTS: The main
      disease manifestations included myelitis (68.4%), headache (63.2%), abnormal
      vision (63.2%), fever (52.6%), ataxia (36.8%), psychosis (31.6%), dyskinesia
      (15.8%), dementia (15.8%) and seizure (10.5%). Seventeen patients had brain
      abnormalities (89.5%), of which eight (42.1%) revealed the characteristic radial
      enhancing and laminar patterns. Cortical abnormalities were found in four
      patients (21.1%). Other abnormalities were found in the hypothalamus, midbrain,
      pons, medulla cerebellum, meninges and skull. Eleven patients had longitudinally
      extensive spinal cord lesions. CSF abnormalities were detected in all patients.
      Pathological examinations of four patients revealed extensive inflammation, with
      prominent perivascular B cells and T cells. Abundant antibody-secreting cells
      were noted in the interstitial and perivascular spaces. Immunohistochemical
      analysis showed loss of astrocytes and neurons. CONCLUSION: The present patients
      with positive GFAP-immunoglobulin G are highly similar to autoimmune GFAP
      astrocytopathy, described in a recent report. The features of the neuropathology
      and immunopathology of GFAP astrocytopathies were perivascular inflammation and
      loss of astrocytes and neurons.

PMID- 29193474
TI  - Copper(0) Mediated Single Electron Transfer Controlled Radical Polymerization
      toward C?F Bonds on Poly(vinylidene fluoride).
AB  - The first copper(0) mediated controlled radical polymerization (CRP) of methyl
      methacrylate (MMA) toward C?F bonds onto poly(vinylidene fluoride) (PVDF) is
      reported with rather high activity. By avoiding the halogen exchange, Cu0 instead
      of CuI complexes utilized as catalyst is responsible for the significantly
      improved polymerization activity. Using F?H decoupled nuclear magnetic resonance
      technique, the grafting sites onto PVDF are finely located. From this, detailed
      topologic information including the grafting density, average length of each side
      chain, along with the overall grafted content of PMMA, is detected by tracking
      the polymerization as a function of time. This work offers not only a facile CRP
      strategy based on inactive C?F bonds but also a deep insight into the cleavage of
      F-bearing compounds in organic chemistry.

PMID- 29193475
TI  - Editorial: Diversity and culture: threads in a golden tapestry which nurses have
      the privilege to enact and the responsibility to preserve.

PMID- 29193476
TI  - Mere social knowledge impacts children's consumption and categorization of foods.
AB  - How does social information affect the perception of taste early in life? Does
      mere knowledge of other people's food preferences impact children's own
      experience when eating? In Experiment 1, 5- and 6-year-old children consumed more
      of a food described as popular with other children than a food that was described
      as unpopular with other children, even though the two foods were identical. In
      Experiment 2, children ate more of a food described as popular with children than
      a food described as popular with adults. Experiment 3 tested whether different
      perceptual experiences of otherwise identical foods contributed to the mechanisms
      underlying children's consumption. After sampling both endpoints of a sweet-to
      sour range (applesauce with 0 mL or 5mL of lemon juice added), children were
      asked to taste and categorize applesauce samples with varying amounts of lemon
      juice added. When classifying ambiguous samples that were near the midpoint of
      the range (2 mL and 3 mL), children were more likely to categorize popular foods
      as sweet as compared to unpopular foods. Together, these findings provide
      evidence that social information plays a powerful role in guiding children's
      consumption and perception of foods. Broader links to the sociality of food
      selection are discussed.

PMID- 29193477
TI  - Outcomes of endoscopic ultrasound-guided pancreatic FNAC diagnosis for solid and
      cystic lesions at Manchester Royal Infirmary based upon the Papanicolaou Society
      of Cytopathology pancreaticobiliary terminology classification scheme.
AB  - OBJECTIVE: To compare endoscopic ultrasound (EUS)-FNAC diagnosis of pancreatic
      lesions with patient outcome based upon the Papanicolaou Society of Cytopathology
      pancreaticobiliary terminology classification scheme diagnostic categories: Panc
      1 (non-diagnostic); Panc 2 (negative for malignancy/neoplasia); Panc 3
      (atypical); Panc 4B (neoplastic, benign); Panc 4O (neoplastic, other); Panc 5
      (suspicious of malignancy); and Panc 6 (positive/malignant). METHODS: All EUS-FNA
      pancreas specimens taken at Manchester Royal Infirmary in 2015 were prospectively
      classified according to the above scheme at the time of cytology reporting and
      data recorded prospectively. Subsequently, outcomes based on clinical follow-up
      or histopathology diagnosis were compared with the cytology diagnosis. RESULTS:
      120 EUS-FNA pancreas specimens from 111 patients were received, of which 112
      (93.3%) specimens had follow-up data. There were 79 and 41 EUS-FNA pancreas
      specimens from solid and cystic lesions, respectively. Based on the cytology
      diagnosis the specimens were classified as Panc 1 (7.5%), Panc 2 (33.3%), Panc 3
      (2.5%), Panc 4B (2.5%), Panc 4O (15.0%), Panc 5 (3.3%) and Panc 6 (35.9%). The
      performance indicators for diagnosis of malignancy or neoplasia with malignant
      potential, included sensitivity (95.4%), specificity (100%), positive predictive
      value (100%), negative predictive value (92.3%), false positive rate (0%) and
      false negative rate (4.6%). CONCLUSIONS: The Papanicolaou Society of
      Cytopathology pancreaticobiliary terminology classification scheme is a logical
      system that can easily be introduced in a diagnostic cytopathology service. This
      classification scheme acts as an aid to diagnostic reporting, clear communication
      of significant results including risk of neoplasia/malignancy to clinicians,
      clinical audit and comparison of results with other centres.

PMID- 29193478
TI  - Possible therapeutic effect of carvacrol on asthmatic patients: A randomized,
      double blind, placebo-controlled, Phase II clinical trial.
AB  - The relaxant effects of carvacrol, a phenolic monoterpene, on tracheal smooth
      muscle and its preventive effect on asthmatic animals were reported. The effect
      of carvacrol in asthmatic patients was examined in the placebo group (Group P, n
      = 11) receiving placebo and treatment group (Group C, n = 12), which received
      carvacrol capsule (1.2 mg/kg/day) for 2 months in a double-blind manner.
      Pulmonary function tests, respiratory symptoms, hematological indices, and high
      sensitivity C-reactive protein (hs-CRP) were measured before, 1 and 2 months
      after starting treatment. At the end of treatment period, Pulmonary function
      tests values in Group C were significantly increased (p < .05 to p < .001). Most
      respiratory symptoms were also significantly reduced in Group C at the end of 2
      month treatment (p < .05 to p < .001). Total and differential white blood cell (p
      < .05 to p < .001), as well as serum levels of hs-CRP in Group C were also
      significantly reduced after 2-month treatment with carvacrol (p < .001). Mean
      corpuscular hemoglobin concentration and hematocrit were changed in Group C (p <
      .05 and p < .01, respectively). However, in Group P, there was no significant
      changes in the evaluated parameters. Pulmonary function tests were increased but
      respiratory symptoms, inflammatory cells, and hs-CRP were reduced in asthmatic
      patients who received carvacrol that indicates its therapeutic effect on asthma.

PMID- 29193479
TI  - BCL-XL binds and antagonizes RASSF6 tumor suppressor to suppress p53 expression.
AB  - RASSF6, a member of the tumor suppressor Ras-association domain family proteins,
      induces apoptosis in the caspase-dependent and caspase-independent manners.
      RASSF6 interacts with MDM2 and stabilizes p53. BCL-XL is a prosurvival member of
      BCL-2 family proteins. BCL-XL directly inhibits proapoptotic BAX and BAK. BCL-XL
      also traps tBID, a proapoptotic activator BH3-only protein, and sequesters p53.
      In addition, BCL-XL regulates the mitochondrial membrane permeability via voltage
      dependent anion channel. In these manners, BCL-XL plays an antiapoptotic role. We
      report the interaction of BCL-XL with RASSF6. BCL-XL inhibits the interaction
      between RASSF6 and MDM2 and suppresses p53 expression. Consequently, BCL-XL
      antagonizes RASSF6-mediated apoptosis. Thus, the inhibition of RASSF6-mediated
      apoptosis also underlies the prosurvival role of BCL-XL.

PMID- 29193480
TI  - Rhabdomyolysis and fluctuating asymptomatic hyperCKemia associated with CACNA1S
      variant.
AB  - BACKGROUND AND PURPOSE: CACNA1S encodes Cav 1.1, a voltage sensor for muscle
      excitation-contraction coupling, which activates the ryanodine receptor 1 (RYR1)
      leading to calcium release from the sarcoplasmic reticulum. CACNA1S mutations
      cause hypokalemic periodic paralysis, malignant hyperthermia and congenital
      myopathy. RYR1 mutations result in congenital myopathy, malignant hyperthermia
      and rhabdomyolysis. METHODS: The aim was to describe a novel phenotype associated
      with a CACNA1S variant at a site previously linked to hypokalemic periodic
      paralysis. RESULTS: The patient presented with fluctuating asymptomatic creatine
      kinase elevation after an episode of rhabdomyolysis but has no history of
      periodic paralysis. His muscle biopsy showed core-like structures occurring
      mainly in type 2 fibers. He carries a novel Cav 1.1 variant (p.Arg528Leu)
      affecting a highly conserved amino acid. Different mutations at the same location
      cause hypokalemic periodic paralysis. CONCLUSION: This case underscores the
      similarity between the phenotypes caused by mutations in two functionally linked
      proteins, RYR1 and Cav 1.1.

PMID- 29193481
TI  - Instilling hope for a brighter future: A mixed-method mentoring support programme
      for individuals with and recovered from anorexia nervosa.
AB  - AIMS AND OBJECTIVES: To investigate the feasibility of a 13-week mentoring
      programme in providing social support to promote hope for recovery in anorexia
      nervosa. BACKGROUND: With no clear first-line psychological treatment for people
      with anorexia nervosa, mentoring support programmes, as an adjunct to treatment,
      may provide the social support necessary to promote hope for recovery. DESIGN: A
      mixed-method study; participatory action research. METHODS: Women (n = 11),
      recovering and who had recovered from anorexia nervosa, participated in the
      programme and completed self-report questionnaires related to quality of life,
      distress and the mentoring relationship at different time points. Qualitative
      feedback from logbooks, workshop evaluation questionnaires, interviews and focus
      groups was also collected to assess the programme's acceptability. RESULTS:
      General compliance for completing most study outcome questionnaires was 90%;
      however, the mentoring relationship questionnaires were not completed to the same
      degree. Five key themes emerged from the focus group/interview data: (i) she
      understands me and could relate to me; (ii) reconnecting with the world-asking
      questions and being challenged; (iii) mentors' altruistic motivations and the
      transformation and discovery of self; (iv) instilling hope-recovery is possible;
      and (v) effective communication-the key to successful mentoring. CONCLUSIONS:
      Further research is needed; however, the results provide preliminary support for
      the mentoring programme's feasibility as an adjunct to treatment. We found that
      having someone who understands, to talk and share with, met a clear need for
      people with anorexia nervosa. RELEVANCE TO CLINICAL PRACTICE: While further
      research is warranted mentoring support or recovered mentors, may play a
      potentially valuable role in supporting those in community settings.

PMID- 29193482
TI  - Comments on "Strategies for reduction in the duration of intravenous drug use:
      Interest of drug tracers as quality indicators to improve intravenous to oral
      switch".

PMID- 29193483
TI  - Isomerization of Allylic Alcohols to Ketones Catalyzed by Well-Defined Iron PNP
      Pincer Catalysts.
AB  - [Fe(PNP)(CO)HCl] (PNP=di-(2-diisopropylphosphanyl-ethyl)amine), activated in situ
      with KOtBu, is a highly active catalyst for the isomerization of allylic alcohols
      to ketones without an external hydrogen supply. High reaction rates were obtained
      at 80  degrees C, but the catalyst is also sufficiently active at room
      temperature with most substrates. The reaction follows a self-hydrogen-borrowing
      mechanism, as verified by DFT calculations. An alternative isomerization through
      alkene insertion and beta-hydride elimination could be excluded on the basis of a
      much higher barrier. In alcoholic solvents, the ketone product is further reduced
      to the saturated alcohol.

PMID- 29193485
TI  - Roland Hauspie (April 8, 1948-April 25, 2017).

PMID- 29193486
TI  - Characterization of Ras k 1 a novel major allergen in Indian mackerel and
      identification of parvalbumin as the major fish allergen in 33 Asia-Pacific fish
      species.
AB  - BACKGROUND: Fish is a well-recognized cause of food allergy and anaphylaxis. The
      evolutionary and taxonomic diversity of the various consumed fish species pose a
      challenge in the identification and characterization of the major fish allergens
      critical for reliable diagnostics. Globally, fish is a rising cause of food
      allergy complicated by a large under-investigated variety of species as well as
      increasing global tourism and trade. This is the first comprehensive study on
      allergen profiles of heat-processed fish from Vietnam. OBJECTIVE: The aim of this
      study was to identify the major heat-stable allergens from frequently exported
      Asia-Pacific freshwater and marine fish and to characterize the major allergen
      parvalbumin (PV) from one of the most consumed and exported fish species from
      Asia, the Indian mackerel (Rastrelliger kanagurta). METHODS: Heated protein
      extracts from 33 fish species were separated by gel electrophoresis. PV isoforms
      were identified by immunoblotting utilizing 3 different PV-specific monoclonal
      and polyclonal antibodies and further characterized by mass spectrometry. IgE
      reactivity was investigated using sera from 21 patients with confirmed fish
      allergy. RESULTS: Heat-stable IgE-reactive PVs, with up to 5 isoforms per
      species, were identified in all 33 analysed fish species. In the Indian mackerel,
      7 PV isoforms were identified by 2D-gel electrophoresis combined with mass
      spectrometric analyses. The amino acid sequence deduced from cDNA of the most
      expressed isoform showed a high identity (>90%) to PVs from 2 other mackerel
      species. CONCLUSIONS AND CLINICAL RELEVANCE: Different PVs were identified as the
      major heat-stable allergens in all 33 analysed freshwater and marine fish species
      from Vietnam, many of which are exported world-wide and 21 species that have
      never been investigated before. The Indian mackerel PV represents a novel fish
      allergen, now officially registered as Ras k 1. Improved diagnostics for fish
      allergy against Asia-Pacific species should be developed with focus on PV.

PMID- 29193484
TI  - Network dynamics engaged in the modulation of motor behavior in stroke patients.
AB  - Stroke patients with motor deficits typically feature enhanced neural activity in
      several cortical areas when moving their affected hand. However, also healthy
      subjects may show higher levels of neural activity in tasks with higher motor
      demands. Therefore, the question arises to what extent stroke-related
      overactivity reflects performance-level-associated recruitment of neural
      resources rather than stroke-induced neural reorganization. We here investigated
      which areas in the lesioned brain enable the flexible adaption to varying motor
      demands compared to healthy subjects. Accordingly, eleven well-recovered left
      hemispheric chronic stroke patients were scanned using functional magnetic
      resonance imaging. Motor system activity was assessed for fist closures at
      increasing movement frequencies performed with the affected/right or
      unaffected/left hand. In patients, an increasing movement rate of the affected
      hand was associated with stronger neural activity in ipsilesional/left primary
      motor cortex (M1) but unlike in healthy controls also in contralesional/right
      dorsolateral premotor cortex (PMd) and contralesional/right superior parietal
      lobule (SPL). Connectivity analyses using dynamic causal modeling revealed
      stronger coupling of right SPL onto affected/left M1 in patients but not in
      controls when moving the affected/right hand independent of the movement speed.
      Furthermore, coupling of right SPL was positively coupled with the "active"
      ipsilesional/left M1 when stroke patients moved their affected/right hand with
      increasing movement frequency. In summary, these findings are compatible with a
      supportive role of right SPL with respect to motor function of the paretic hand
      in the reorganized brain.

PMID- 29193487
TI  - Impaired fasting glucose and the metabolic profile in Danish children and
      adolescents with normal weight, overweight, or obesity.
AB  - OBJECTIVE: Whether the definitions of impaired fasting glucose (IFG) from the
      American Diabetes Association (ADA) and the World Health Organization (WHO)
      differentially impact estimates of the metabolic profile and IFG-related
      comorbidities in Danish children and adolescents is unknown. METHODS: Two
      thousand one hundred and fifty four (979 boys) children and adolescents with
      overweight or obesity (median age 12 years) and 1824 (728 boys) children with
      normal weight (median age 12 years) from The Danish Childhood Obesity Biobank
      were studied. Anthropometrics, blood pressure, puberty, and fasting
      concentrations of glucose, insulin, glycosylated hemoglobin (HbA1c), and lipids
      were measured. RESULTS: About 14.1% of participants with overweight or obesity
      exhibited IFG according to the ADA and 3.5% according to the WHO definition.
      Among individuals with normal weight, the corresponding prevalences were 4.3% and
      0.3%. IFG was associated with a higher systolic blood pressure, higher
      concentrations of HbA1c, insulin, C-peptide (P < .0001) and triglycerides (P =
      .03), and lower HOMA2-IS and HOMA2-B (P < .0001) independent of sex, age,
      puberty, waist-to-height ratio, and degree of obesity. Furthermore, IFG was
      associated with a higher risk for hypertension (OR = 1.66 [95%CI: 1.21; 2.28], P
      = .002) and dyslipidemia (OR = 1.90 [95%CI: 1.38; 2.56], P < .0001) compared with
      the group without IFG independent of age, sex, and puberty. CONCLUSIONS: The
      prevalence of IFG, when applying the ADA criterion compared with the WHO
      criterion, was 4 times higher in individuals with overweight and obesity and 14
      times higher in individuals with normal weight in this study sample of children
      and adolescents. IFG was associated with a higher risk of hypertension and
      dyslipidemia compared with their normoglycemic peers regardless of the definition
      applied.

PMID- 29193488
TI  - A path to understanding autoimmune GFAP astrocytopathy.

PMID- 29193489
TI  - Prognostic value of pathologic grade for patients with oral squamous cell
      carcinoma: Methodological issues.

PMID- 29193490
TI  - The Eastern side of the Westernmost Europeans: Insights from subclades within Y
      chromosome haplogroup J-M304.
AB  - OBJECTIVES: We examined internal lineages and haplotype diversity in Portuguese
      samples belonging to J-M304 to improve the spatial and temporal understanding of
      the introduction of this haplogroup in Iberia, using the available knowledge
      about the phylogeography of its main branches, J1-M267 and J2-M172. METHODS: A
      total of 110 males of Portuguese descent were analyzed for 17 Y-chromosome bi
      allelic markers and seven Y-chromosome short tandem repeats (Y-STR) loci.
      RESULTS: Among J1-M267 individuals (n = 36), five different sub-haplogroups were
      identified, with the most common being J1a2b2-L147.1 (~72%), which encompassed
      the majority of representatives of the J1a2b-P58 subclade. One sample belonged to
      the rare J1a1-M365.1 lineage and presented a core Y-STR haplotype consistent with
      the Iberian settlement during the fifth century by the Alans, a people of Iranian
      heritage. The analysis of J2-M172 Portuguese males (n = 74) enabled the detection
      of the two main subclades at very dissimilar frequencies, J2a-M410 (~80%) and J2b
      M12 (~20%), among which the most common branches were J2a1(xJ2a1b,h)-L26 (22.9%),
      J2a1b(xJ2a1b1)-M67 (20.3%), J2a1h-L24 (27%), and J2b2-M241 (20.3%). CONCLUSIONS:
      While previous inferences based on modern haplogroup J Y-chromosomes implicated a
      main Neolithic dissemination, here we propose a later arrival of J lineages into
      Iberia using a combination of novel Portuguese Y-chromosomal data and recent
      evidence from ancient DNA. Our analysis suggests that a substantial tranche of J1
      M267 lineages was likely carried into the Iberian Peninsula as a consequence of
      the trans-Mediterranean contacts during the first millennium BC, while most of
      the J2-M172 lineages may be associated with post-Neolithic population movements
      within Europe.

PMID- 29193491
TI  - Age-related changes in the dynamics of fear-related regulation in early
      childhood.
AB  - Self-regulation is a dynamic process wherein executive processes (EP) delay,
      minimize or desist prepotent responses (PR) that arise in situations that
      threaten well-being. It is generally assumed that, over the course of early
      childhood, children expand and more effectively deploy their repertoire of EP
      related strategies to regulate PR. However, longitudinal tests of these
      assumptions are scarce in part because self-regulation has been mostly studied as
      a static construct. This study engages dynamic systems modeling to examine
      developmental changes in self-regulation between ages 2 and 5 years. Second-by
      second time-series data derived from behavioral observations of 112 children (63
      boys) faced with novel laboratory-based situations designed to elicit wariness,
      hesitation, and fear were modeled using differential equation models designed to
      capture age-related changes in the intrinsic dynamics and bidirectional coupling
      of PR (fear/wariness) and EP (strategy use). Results revealed that dynamic models
      allow for the conceptualization and measurement of fear regulation as intrinsic
      processes as well as direct and indirect coupling between PR and EP. Several
      patterns of age-related changes were in line with developmental theory suggesting
      that PR weakened and was regulated more quickly and efficiently by EP at age 5
      than at age 2. However, most findings were in the intrinsic dynamics and
      moderating influences between PR and EP rather than direct influences. The
      findings illustrate the precision with which specific aspects of self-regulation
      can be articulated using dynamic systems models, and how such models can be used
      to describe the development of self-regulation in nuanced and theoretically
      meaningful ways.

PMID- 29193492
TI  - Perfusion measures for symptom severity and differential outcome of
      revascularization in limb ischemia: Preliminary results with arterial spin
      labeling reactive hyperemia.
AB  - BACKGROUND: Previously, a theoretical model based on microvascular physiology was
      established to facilitate the interpretation of calf perfusion dynamics recorded
      by arterial spin labeling (ASL). PURPOSE: To investigate the clinical relevance
      of novel perfusion indices by comparing them to the symptoms, response to
      revascularization, and short-term functional outcome in patients with peripheral
      arterial disease (PAD). STUDY TYPE: Prospective cohort study. POPULATION:
      Nineteen patients with PAD. FIELD STRENGTH/SEQUENCE: Pulsed ASL at 3T.
      ASSESSMENT: The mid-calf reactive hyperemia induced by 2 minutes of arterial
      occlusion was recorded in PAD patients. The perfusion responses were
      characterized by the peak, time-to-peak, and physiological model-derived indices
      including the baseline perfusion fr , arterial resistance Ra , and compliance Ca
      , and sensitivity gATP and response time tauATP of downstream microvasculature to
      metabolic stress. These indices were compared to the disease severity and outcome
      within 6 months after revascularization assessed by self-reported symptoms and
      the ankle-brachial index. Disease severity was categorized as asymptomatic,
      claudication, or critical limb ischemia. The outcome was categorized as symptom
      resolved or limited improvement. STATISTICAL TESTS: Severity and outcome groups
      were compared using Mann-Whitney and Kruskal-Wallis tests with Holm-Sidak
      adjustments. RESULTS: The peak perfusion decreased and model arterial resistance
      increased progressively with increasing severity of limb ischemia (P = 0.0402 and
      0.0413, respectively). Eleven patients had a successful endovascular procedure,
      including six patients who had symptoms resolved, four patients who had remaining
      leg pain, and one patient lost to follow-up. The subjects with limited
      improvement had significantly lower preintervention microvascular sensitivity
      gATP than those with symptoms resolved (8.72 +/- 1.46 vs. 4.93 +/- 0.91, P =
      0.0466). DATA CONCLUSION: ASL reactive hyperemia reflects multiple aspects of the
      pathophysiology. Measures of macrovascular arterial disease are related to the
      manifested symptom severity, whereas preintervention gATP associated with
      microvascular dysfunction is related to prognosis following revascularization.
      LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging
      2018;47:1578-1588.

PMID- 29193493
TI  - The Sleep Condition Indicator: reference values derived from a sample of 200 000
      adults.
AB  - The Sleep Condition Indicator (SCI) is an eight-item rating scale that was
      developed to screen for insomnia disorder based on DSM-5 criteria. It has been
      shown previously to have good psychometric properties among several language
      translations. We developed age- and sex-referenced values for the SCI to assist
      the evaluation of insomnia in everyday clinical practice. A random sample of 200
      000 individuals (58% women, mean age: 31 +/- 13 years) was selected from those
      who had completed the SCI via several internet platforms. Descriptive and
      inferential methods were applied to generate reference data and indices of
      reliable change for the SCI for men and women across the age deciles 16-25, 26
      35, 36-45, 46-55, 56-65 and 66-75 years. The mean SCI score for the full sample
      was 14.97 +/- 5.93. Overall, women scored worse than men (14.29 +/- 5.83 versus
      15.90 +/- 5.94; mean difference: -1.60, eta2  = 0.018, Cohen's d = 0.272) and
      those of older age scored worse than those younger (-0.057 points per year, 95%
      confidence interval (CI): -0.059 to -0.055) relative to age 16-25 years. The
      Reliable Change Index was established at seven scale points. In conclusion, the
      SCI is a useful instrument for clinicians and researchers that can help them to
      screen for insomnia, compare completers to individuals of similar age and sex and
      establish whether a reliable change was achieved following treatment.

PMID- 29193494
TI  - "It's good, they're like me; the same but different." An interpretative
      phenomenological analysis of the identities of women with down's syndrome.
AB  - BACKGROUND: For people with disabilities, identity formation is based on
      responses to hierarchical values determined by able populations. Some adopt a
      disability identity, whereas others may seek to conceal their disability. No
      research has focused on how women with Down's Syndrome form an identity. DESIGN:
      Eight women with Down's Syndrome took part in semi-structured interviews designed
      to find out more about their individual and shared identities. The transcripts
      were analysed using interpretive phenomenological analysis. FINDINGS: Negative
      assumptions of others and oppressive, paternalistic care often lead to a lack of
      ownership over narratives. "Finding a place in society" is an attempt to
      challenge this and gain a sense of ownership over their lives. CONCLUSIONS: This
      research uncovered the individual and shared identities that women with Down's
      Syndrome construct. Services need to be aware of the role they have in supporting
      these women to develop autonomy and ownership over their lives.

PMID- 29193495
TI  - Premature birth affects the degree of airway dysanapsis and mechanical
      ventilatory constraints.
AB  - NEW FINDINGS: What is the central question of this study? Adult survivors of
      preterm birth without (PRE) and with bronchopulmonary dysplasia (BPD) have
      airflow obstruction at rest and significant mechanical ventilatory constraints
      during exercise compared with those born at full term (CON). Do PRE/BPD have
      smaller airways, indexed via the dysanapsis ratio, than CON? What is the main
      finding and its importance? The dysanapsis ratio was significantly smaller in BPD
      and PRE compared with CON, with BPD having the smallest dysanapsis ratio. These
      data suggest that airflow obstruction in PRE and BPD might be because of smaller
      airways than CON. Adult survivors of very preterm birth (<=32 weeks gestational
      age) without (PRE) and with bronchopulmonary dysplasia (BPD) have obstructive
      lung disease as evidenced by reduced expiratory airflow at rest and have
      significant mechanical ventilatory constraints during exercise. Airflow
      obstruction, in any conditions, could be attributable to several factors,
      including small airways. PRE and/or BPD could have smaller airways than their
      counterparts born at full term (CON) owing to a greater degree of dysanaptic
      airway development during the pre- and/or postnatal period. Thus, the purpose of
      the present study was to compare the dysanapsis ratio (DR), as an index of airway
      size, between PRE, BPD and CON. To do so, we calculated DR in PRE (n = 21), BPD
      (n = 14) and CON (n = 34) individuals and examined flow-volume loops at rest and
      during submaximal exercise. The DR, using multiple estimates of static recoil
      pressure, was significantly smaller in PRE and BPD (0.16 +/- 0.05 and 0.10 +/-
      0.03 a.u.) compared with CON (0.22 +/- 0.04 a.u.; both P < 0.001) and smallest in
      BPD (P < 0.001). The DR was significantly correlated with peak expiratory airflow
      at rest (r = 0.42; P < 0.001) and the extent of expiratory flow limitation during
      exercise (r = 0.60; P < 0.001). Our findings suggest that PRE/BPD might have
      anatomically smaller airways than CON, which might help to explain their lower
      expiratory airflow rate at rest and during exercise and further our understanding
      of the consequences of preterm birth and neonatal O2 therapy.

PMID- 29193496
TI  - Macrolide Synthesis through Intramolecular Oxidative Cross-Coupling of Alkenes.
AB  - A RhIII -catalyzed intramolecular oxidative cross-coupling between double bonds
      for the synthesis of macrolides is described. Under the optimized reaction
      conditions, macrocycles containing a diene moiety can be formed in reasonable
      yields and with excellent chemo- and stereoselectivity. This method provides an
      efficient approach to synthesize macrocyclic compounds containing a 1,3
      conjugated diene structure.

PMID- 29193497
TI  - Stereochemical Definition of the Natural Product (6R,10R,13R,
      14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R,33R,34R,36S,37S,39R)-Azaspiracid-3 by
      Total Synthesis and Comparative Analyses.
AB  - The previously accepted structure of the marine toxin azaspiracid-3 is revised
      based upon an original convergent and stereoselective total synthesis of the
      natural product. The development of a structural revision hypothesis, its
      testing, and corroboration are reported. Synthetic
      (6R,10R,13R,14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R, 33R,34R,36S,37S,39R)
      azaspiracid-3 chromatographically and spectroscopically matched naturally
      occurring azaspiracid-3, whereas the previously assigned 20R epimer did not.

PMID- 29193498
TI  - The impact of shift work on intensive care nurses' lives outside work: A cross
      sectional study.
AB  - AIMS AND OBJECTIVES: To examine how shift work affects intensive care nurses'
      lives outside work. BACKGROUND: Shift work is unavoidable for many nurses. When
      attempting to minimise negative effects of shift work, it is important to
      identify areas which affect nurses working shifts. DESIGN: A cross-sectional
      study. METHODS: A questionnaire survey among Danish intensive care nurses
      concerning experiences with shift work and family life, spare time activities,
      sleep and health. RESULTS: A total of 114 nurses (88%) participated. Shift work
      was found to influence the opportunities for spare time activities, and about 25%
      of both evening- and night-shift groups found that working shifts sometimes led
      to social isolation. A total of 58% of nurses working evening shifts sometimes to
      very often experienced having trouble falling asleep when working shifts. Night
      shift workers had a higher percentage of physical and mental symptoms when
      working shifts compared with evening-shift workers, with mood swings and
      headaches being the most common. The median score for thriving on working shifts
      was 8 (IQR 5-9) for evening-shift workers and 8 (IQR 7-9) for night-shift workers
      (scale 0-10 with 10 being the highest level of thriving). CONCLUSION: Shift
      workers reported that working shifts had a negative impact on life outside work.
      Opportunities for participating in spare time activities and difficulties falling
      asleep after shifts were the main issues for evening-shift workers, whereas
      physical symptoms such as headaches and mood swings were more dominant among
      night-shift workers. Despite the negative effects, the participants generally
      thrived on working shifts. RELEVANCE TO CLINICAL PRACTICE: By identifying
      modifiable areas which negatively influence life outside work when working
      shifts, it will be possible subsequently to plan interventions aimed at
      decreasing the negative effects. Interventions may include nurses having
      increased influence on their work schedules and education in sleep hygiene and
      dietary habits.

PMID- 29193499
TI  - Screening, staging, and naming of presymptomatic type 1 diabetes.

PMID- 29193500
TI  - Stroke patients with familial hypercholesterolemia: need for detection and
      aggressive treatment.

PMID- 29193501
TI  - Subspecialty preferences among neurologists of the future.
AB  - BACKGROUND AND PURPOSE: In the era of neurological subspecialization, most
      neurologists will have a field of specialist interest. The aim of this cross
      sectional multinational study was to identify the key areas of interest among
      trainees or junior specialists, assess the potential influence of an interest in
      research and consider the results in light of population needs. METHODS: A total
      of 300 residents and junior neurologists who received a bursary to attend the
      European Academy of Neurology conference were invited to participate in this
      study. Demographic and work-related characteristics, as well as main subspecialty
      of choice, were examined via an anonymous electronic questionnaire. Participants
      holding a higher degree (PhD/MD) or working in research posts were considered
      research oriented. RESULTS: In total, 191 neurologists in training or junior
      specialists responded (response rate 63.7%). Full data were available for 187
      participants (59.4% females). The study sample had a mean age of 30.5 +/- 3.4
      (range 25-45) years. The most popular subspecialty was movement disorders
      (18.2%), followed by multiple sclerosis (11.2%) and epilepsy (10.2%). This did
      not differ significantly between the participants who were or were not research
      oriented. CONCLUSIONS: There is a potential mismatch between the interests of
      trainees and the future needs of the populations they serve, which is important
      to identify for workforce planning.

PMID- 29193503
TI  - Mobile-based patient-provider communication in cancer survivors: The roles of
      health literacy and patient activation.
AB  - OBJECTIVE: Thanks to rapid penetration of mobile tools, more and more cancer
      survivors have adopted mobile-based patient-provider communication (MBPPC). The
      relationship between MBPPC and patients' health outcomes, however, remains
      unclear; how health literacy and patient activation interact with such
      relationship is unexplored. METHODS: Data were drawn from National Cancer
      Institute's Health Information National Trends Survey 4 Cycle 3. A sample of 459
      cancer survivors were included in the analysis. Based on the 3-stage model of
      health promotion using interactive media, this study empirically tested a
      moderated mediation model. RESULTS: MBPPC (eg, patient use of email, text
      message, mobile app, and social media to communicate with providers) had no
      direct effect on cancer survivors' emotional health. Instead, health literacy
      completely mediated this path. Patient activation positively moderated the effect
      of health literacy on emotional health and further increased the indirect effect
      of MBPPC on emotional health. CONCLUSIONS: MBPPC alone does not directly result
      in better emotional health outcomes; health literacy is the key to realize its
      health benefits; patient activation significantly strengthens the effects of
      MBPPC. As we embrace the mHealth movement, innovative programs are needed to
      promote MBPPC, and improve health literacy and activation of cancer survivors,
      particularly in underserved communities, to reduce health disparities.

PMID- 29193504
TI  - Cohort-based income gradients in obesity among U.S. adults.
AB  - OBJECTIVES: No studies have focused on socioeconomic disparities in obesity
      within and between cohorts. Our objectives were to examine income gradients in
      obesity between birth-cohorts (inter-cohort variations) and within each birth
      cohort (intra-cohort variations) by gender and race/ethnicity. METHODS: Our
      sample includes 56,820 white and black adults from pooled, cross-sectional
      National Health and Nutrition Examination Surveys (1971-2012). We fit a series of
      logistic hierarchical Age-Period-Cohort models to control for the effects of age
      and period, simultaneously. Predicted probabilities of obesity by poverty-to
      income ratio were estimated and graphed for 5-year cohort groups from 1901-1990.
      We also stratified this relationship for four gender and racial/ethnic subgroups.
      RESULTS: Obesity disparities due to income were weaker for post-World War I and
      II generations, specifically the mid-1920s and the mid-1940s to 1950s cohorts,
      than for other cohorts. In contrast, we found greater income gradients in obesity
      among cohorts from the 1930s to mid-1940s and mid-1960s to 1970s. Moreover,
      obesity disparities due to income across cohorts vary markedly by gender and
      race/ethnicity. White women with higher income consistently exhibited a lower
      likelihood of obesity than those with lower income since early 1900s cohorts;
      whereas, black men with higher income exhibited higher risks of obesity than
      those with lower income in most cohorts. CONCLUSIONS: Our findings suggest that
      strategies that address race and/or gender inequalities in obesity should be
      cognizant of significant historical factors that may be unique to cohorts. Period
      based approaches that ignore life-course experiences captured in significant
      cohort-based experiences may limit the utility of policies and interventions.

PMID- 29193502
TI  - FOXP3 mutations causing early-onset insulin-requiring diabetes but without other
      features of immune dysregulation, polyendocrinopathy, enteropathy, X-linked
      syndrome.
AB  - Diabetes occurs in 1/90 000 to 1/160 000 births and when diagnosed under 6 months
      of age is very likely to have a primary genetic cause. FOXP3 encodes a
      transcription factor critical for T regulatory cell function and mutations are
      known to cause "immune dysregulation, polyendocrinopathy (including insulin
      requiring diabetes), enteropathy, X-linked" (IPEX) syndrome. This condition is
      often fatal unless patients receive a bone-marrow transplant. Here we describe
      the phenotype of male neonates and infants who had insulin-requiring diabetes
      without other features of IPEX syndrome and were found to have mutations in
      FOXP3. Whole-exome or next generation sequencing of genes of interest was carried
      out in subjects with isolated neonatal diabetes without a known genetic cause. RT
      PCR was carried out to investigate the effects on RNA splicing of a novel
      intronic splice-site variant. Four male subjects were found to have FOXP3
      variants in the hemizygous state: p.Arg114Trp, p.Arg347His, p.Lys393Met, and
      c.1044+5G>A which was detected in 2 unrelated probands and in a brother diagnosed
      with diabetes at 2.1 years of age. Of these, p.Arg114Trp is likely a benign rare
      variant found in individuals of Ashkenazi Jewish ancestry and p.Arg347His has
      been previously described in patients with classic IPEX syndrome. The p.Lys393Met
      and c.1044+5G>A variants are novel to this study. RT-PCR studies of the
      c.1044+5G>A splice variant confirmed it affected RNA splicing by generating both
      a wild type and truncated transcript. We conclude that FOXP3 mutations can cause
      early-onset insulin-requiring diabetes with or without other features of IPEX
      syndrome.

PMID- 29193505
TI  - A structural model of family empowerment for families of children with special
      needs.
AB  - AIMS AND OBJECTIVES: To explain and predict family empowerment in families of
      children with special needs. BACKGROUND: Family empowerment of families of
      children with special needs can be explained using the Double ABCX model.
      Although constant stressors such as parenting stress and family demands can have
      negative effects on family empowerment, family resources and parenting efficacy
      can mediate the negative effect through effective coping strategies. DESIGN: A
      cross-sectional research design was employed. METHODS: A survey was conducted
      with 240 parents of children with special needs. Upon exclusion of four responses
      deemed inadequate to the statistics process, 236 responses were selected for the
      analysis. Based on the items used in the previous research, we used the scale of
      family demands 38, the scale of parenting stress 24, the scale of parenting
      efficacy 37, the scale of pattern of organisation 30, the scale of communication
      process 16 and the scale of family empowerment 32. RESULTS: In families of
      children with special needs, parenting stress had a negative effect on parenting
      efficacy and family resources, namely, pattern of organisation and communication
      process. Family needs had a positive effect on parenting efficacy. Parenting
      stress and family demands influenced family empowerment through parenting
      efficacy and family resources (pattern of organisation and communication
      process), while parenting efficacy contributed to family empowerment.
      CONCLUSIONS: This study empirically analysed the usefulness of the Double ABCX
      model in predicting family empowerment. Family resource factors (organisation
      pattern and communication process) and perception or judgement factors (such as
      parenting efficacy) were found to mediate the negative impact of various
      stressors experienced by families of children with special needs. RELEVANCE TO
      CLINICAL PRACTICE: The study findings suggest that clinical practice and
      management should focus on providing efficient intervention methods to lower
      stress in families of children with special needs. Reinforcing factors
      contributing to family empowerment, such as parenting efficacy, organisation
      pattern and communication process, will alleviate families' stress, resulting in
      a positive educational and developmental impact on children with special needs.

PMID- 29193506
TI  - Synthesis and Stability of Lanthanum Superhydrides.
AB  - Recent theoretical calculations predict that megabar pressure stabilizes very
      hydrogen-rich simple compounds having new clathrate-like structures and
      remarkable electronic properties including room-temperature superconductivity. X
      ray diffraction and optical studies demonstrate that superhydrides of lanthanum
      can be synthesized with La atoms in an fcc lattice at 170 GPa upon heating to
      about 1000 K. The results match the predicted cubic metallic phase of LaH10
      having cages of thirty-two hydrogen atoms surrounding each La atom. Upon
      decompression, the fcc-based structure undergoes a rhombohedral distortion of the
      La sublattice. The superhydride phases consist of an atomic hydrogen sublattice
      with H-H distances of about 1.1 A, which are close to predictions for solid
      atomic metallic hydrogen at these pressures. With stability below 200 GPa, the
      superhydride is thus the closest analogue to solid atomic metallic hydrogen yet
      to be synthesized and characterized.

PMID- 29193507
TI  - Incidence of antiemetic-induced akathisia in patients at a comprehensive cancer
      center.
AB  - INTRODUCTION: Akathisia is a common and severely disabling medication-induced
      movement disorder. The condition is often missed, and patients suffer for a long
      time until diagnosed and managed properly. It is important to bring awareness to
      the clinicians for early detection and management of akathisia. METHODS: We
      reviewed a 4-year record of patients seen at a comprehensive cancer center for
      anxiety and restlessness. Patients diagnosed with akathisia and the medications
      causing akathisia were identified. Management of akathisia is discussed. RESULTS:
      The results showed that 4.7% of patients developed akathisia while taking
      antiemetic agents to control chemotherapy-induced nausea/vomiting. Early
      detection and management of akathisia resulted in quick recovery and reduced
      patients' suffering. CONCLUSION: Akathisia is an unpleasant feeling of motor
      restlessness with anxiety. Clinicians need to have a full understanding to
      identify the subtle difference between functional anxiety and akathisia.

PMID- 29193508
TI  - Detection of liver fibrosis using qualitative and quantitative MR elastography
      compared to liver surface nodularity measurement, gadoxetic acid uptake, and
      serum markers.
AB  - BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) combining
      different techniques such as MR elastography (MRE) has emerged as a noninvasive
      approach to diagnose and stage liver fibrosis with high accuracy allowing for
      anatomical and functional information. PURPOSE: To assess the diagnostic
      performance of mpMRI including qualitative and quantitative assessment of MRE,
      liver surface nodularity (LSN) measurement, hepatic enhancement ratios
      postgadoxetic acid, and serum markers (APRI, FIB-4) for the detection of liver
      fibrosis. STUDY TYPE: IRB-approved retrospective. SUBJECTS: Eighty-three adult
      patients. FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T MR systems. MRE and T1 -weighted
      postgadoxetic acid sequences. ASSESSMENT: Two independent observers analyzed
      qualitative color-coded MRE maps on a scale of 0-3. Regions of interest were
      drawn to measure liver stiffness on MRE stiffness maps and on pre- and
      postcontrast T1 -weighted images to measure hepatic enhancement ratios. Software
      was used to generate LSN measurements. Histopathology was used as the reference
      standard for diagnosis of liver fibrosis in all patients. STATISTICAL TESTS: A
      multivariable logistic analysis was performed to identify independent predictors
      of liver fibrosis. Receiver operating characteristic (ROC) analysis evaluated the
      performance of each imaging technique for detection of fibrosis, in comparison
      with serum markers. RESULTS: Liver stiffness measured with MRE provided the
      strongest correlation with histopathologic fibrosis stage (r = 0.74, P < 0.001),
      and the highest diagnostic performance for detection of stages F2-F4, F3-F4, and
      F4 (areas under the curve [AUCs] of 0.87, 0.91, and 0.89, respectively, P <
      0.001) compared to other methods. Qualitative assessment of MRE maps showed fair
      to good accuracy for detection of fibrosis (AUC range 0.76-0.84). Multivariable
      logistic analysis identified liver stiffness and FIB-4 as independent predictors
      of fibrosis with AUCs of 0.90 (F2-F4), 0.93 (F3-F4) and 0.92 (F4) when combined.
      DATA CONCLUSION: Liver stiffness measured with MRE showed the best performance
      for detection of liver fibrosis compared to LSN and gadoxetic acid uptake, with
      slight improvement when combined with FIB-4. LEVEL OF EVIDENCE: 3 Technical
      Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1552-1561.

PMID- 29193509
TI  - The Narrowest Band Gap Ever Observed in Molecular Ferroelectrics: Hexane-1,6
      diammonium Pentaiodobismuth(III).
AB  - Narrow band gaps and excellent ferroelectricity are intrinsically paradoxical in
      ferroelectrics as the leakage current caused by an increase in the number of
      thermally excited carriers will lead to a deterioration of ferroelectricity. A
      new molecular ferroelectric, hexane-1,6-diammonium pentaiodobismuth (HDA-BiI5 ),
      was now developed through band gap engineering of organic-inorganic hybrid
      materials. It features an intrinsic band gap of 1.89 eV, and thus represents the
      first molecular ferroelectric with a band gap of less than 2.0 eV.
      Simultaneously, low-temperature solution processing was successfully applied to
      fabricate high-quality ferroelectric thin films based on HDA-BiI5 , for which
      high-precision controllable domain flips were realized. Owing to its narrow band
      gap and excellent ferroelectricity, HDA-BiI5 can be considered as a milestone in
      the exploitation of molecular ferroelectrics, with promising applications in high
      density data storage and photovoltaic conversion.

PMID- 29193510
TI  - Site-Selective Linear Alkylation of Anilides by Cooperative Nickel/Aluminum
      Catalysis.
AB  - We report meta- and para-selective linear alkylation reactions of anilides with
      alkenes by nickel/N-heterocyclic carbene (NHC) and aluminum catalysis. With a
      less bulky NHC, the alkylation reaction of N-methyl-N
      phenylcyclohexanecarboxamides proceeded mainly at the meta position. In contrast,
      a bulky NHC ligand led to the para-selective alkylation of N-sec-alkyl anilides.

PMID- 29193511
TI  - Epidemiology of haemodialysis patients and haemodialysis performance in Nauru.
AB  - AIM: There is limited literature on haemodialysis in island countries in the
      Central Pacific. The primary aim of this study was to report on the epidemiology
      of haemodialysis patients and haemodialysis performance in Nauru. METHODS: We
      obtained registry data from the haemodialysis unit in Nauru to calculate the
      incidence rate, prevalence, and survival probability of haemodialysis patients in
      Nauru. We also reviewed medical records from January 2015 to February 2017 to
      evaluate the haemodialysis performance in Nauru. RESULTS: In total, 177 patients
      received long-term haemodialysis in the Nauru dialysis unit from 1987 to 2017.
      The 1-year, 2-year, and 5-year survival probabilities during the 30-year study
      period were 76.5%, 58.3% and 25.9%, respectively. From 2011 to 2014, the
      incidence rate and prevalence of treated end-stage renal disease in Nauru were
      significantly higher than Australia. From 2015 to 2017, there were 36 patients
      with a median age of 55 years who received long-term haemodialysis. Of these, 25
      patients (69.4%) had diabetes. The median haemoglobin, serum albumin, and urea
      reduction ratio were 9.6 mg/dL, 35 g/L, and 64.7%, respectively. Multivariate
      analysis showed that lower serum albumin and lower urea reduction ratio were
      associated with mortality. CONCLUSION: To our knowledge, this is the first study
      to report the haemodialysis status in Nauru. The epidemiology of haemodialysis
      patients in Nauru is unique in Central Pacific. Improvement of primary health
      care in disease detection and prevention of progression should be considered to
      decrease the need for dialysis and optimise the care of haemodialysis patients in
      Nauru.

PMID- 29193512
TI  - Exertional hypoxemia is more severe in fibrotic interstitial lung disease than in
      COPD.
AB  - BACKGROUND AND OBJECTIVE: Despite its clinical and prognostic significance, few
      studies have evaluated the severity of exertional oxygen desaturation in fibrotic
      interstitial lung disease (ILD). Our objectives were to identify clinical and
      physiological variables that predict the extent of exertional oxygen desaturation
      in fibrotic ILD and to quantify the severity of desaturation compared to chronic
      obstructive pulmonary disease (COPD). METHODS: This retrospective study compared
      the results of 6-min walk test (6MWT) performed while breathing room air in
      fibrotic ILD patients and COPD patients eligible for pulmonary rehabilitation.
      Outcomes included the oxygen saturation (SpO2 ) nadir and the change in SpO2 from
      rest during a 6MWT. Predictor variables were identified on unadjusted analysis,
      followed by multivariate analysis to identify independent predictors of
      desaturation. RESULTS: The study included 134 patients with fibrotic ILD and 274
      patients with COPD. The ILD and COPD cohorts had similar age, sex, frequency of
      major comorbidities, walk distance, baseline SpO2 and baseline Borg dyspnoea
      scores. DLCO was the strongest predictor of desaturation in both cohorts.
      Compared to patients with COPD, ILD patients had significantly lower SpO2 nadir
      values (88.1 +/- 6.4 vs 91.0 +/- 4.6) and greater decrease in SpO2 from baseline
      (7.4 +/- 5.2 vs 4.5 +/- 3.7) after adjusting for demographic features and
      pulmonary physiology (P < 0.0005), with greater between-group differences at
      lower DLCO values. CONCLUSION: Patients with fibrotic ILD have greater oxygen
      desaturation during 6MWT compared to patients with COPD when adjusting for
      demographic features and pulmonary physiology. These findings suggest the need
      for disease-specific studies to evaluate the potential utility of ambulatory
      oxygen in fibrotic ILD.

PMID- 29193513
TI  - Formalising the precepting process: A concept analysis of preceptorship.
AB  - AIMS AND OBJECTIVES: To elucidate the terminology associated with preceptorships,
      articulate an operational description of preceptorship that may be useful in
      formalising the precepting process and provide guidance for constructing a
      clinical environment where precepting can thrive. BACKGROUND: Precepting
      facilitates the transition of nurses into new roles. Precepting may improve
      patient outcomes and safety, as well as enhance nursing satisfaction. Most
      research focuses on preceptor preparation and perceptions. A comprehensive
      operational description of what is required to formalise the precepting process
      is missing from the literature. DESIGN: This concept analysis was completed using
      a combination of Walker and Avant's and Rodger's methods. METHODS: Existing
      literature relating to preceptorship was reviewed. Critical attributes,
      antecedents, consequences and empirical referents were identified. Model,
      contrary, related and borderline cases were developed. RESULTS: Preceptorships
      have the specific attributes of being (i) one-on-one relationships, (ii) embedded
      within formalised programmes, (iii) that evolve over set amounts of time, (iv) to
      systematically facilitate practical experiences. Antecedents include how
      precepting is triggered and organisational supporting activities that may
      facilitate effective precepting. Consequences include new hire preparedness,
      confidence and increased retention. Empirical referents are provided for
      assessing hands-on clinical expertise, individualisation of precepting programmes
      and the preceptor-preceptee relationship. CONCLUSIONS: This concept analysis
      provides a holistic view of the precepting process that shifts the focus from the
      people or checklist to formalised preceptorships. RELEVANCE TO CLINICAL PRACTICE:
      Continuity throughout an organisation's system streamlines the process of hiring
      new employees and transitioning nursing students to practice. Organisational
      policies, dedicated resources and engagement in systematically improving the
      precepting process are critical. Nurse managers must promote and support
      formalised preceptorships by providing preceptors and preceptees the time and
      space needed and fostering a culture that supports preceptorships.

PMID- 29193514
TI  - Kinetics of Thermal Polymerization Can Be Studied during Continuous Cooling.
AB  - It is demonstrated that differential scanning calorimetry can measure the
      kinetics of the thermally initiated polymerization during continuous cooling. The
      measurements are accomplished by switching from fast heating to much slower
      cooling. The study is exemplified by crosslinking polymerization (curing) of
      diglycidyl ether of bisphenol A epoxy and m-phenylenediamine taken in
      stoichiometric and nonstoichiometric ratios and measured under heating and
      cooling conditions. An advanced isoconversional method reveals that the reaction
      in the nonstoichiometric system follows the kinetics of the single-step type. Its
      activation energy is constant and the same for heating and cooling conditions.
      The stoichiometric system exhibits the multistep kinetics characterized by the
      dependencies of the activation energy on temperature that differ qualitatively
      for cooling and heating runs. The discovered differences emphasize the need for
      further systematic studies of the thermal polymerization during continuous
      cooling.

PMID- 29193515
TI  - Gold-Catalyzed Dearomatization of 2-Naphthols with Alkynes.
AB  - The site-selective dearomatization of naphthols is realized in a straightforward
      manner through a gold(I)-catalyzed [3,3]-sigmatropic rearrangement/allene
      functionalization cascade sequence. The method employs readily available
      naphthylpropargyl ethers as starting materials. A range of densely functionalized
      dihydrofurylnaphthalen-2(1H)-ones are obtained in high yields (up to 98 %) and
      extremely mild reaction conditions (reagent grade solvent, air, 10 minute
      reaction time). A complete theoretical elucidation of the reaction machinery is
      also proposed, providing a rationale for important issues such as regio- and
      chemoselectivity.

PMID- 29193516
TI  - The effectiveness of clinical pathway-directed care on hospitalisation-related
      outcomes in patients with severe traumatic brain injury: A quasi-experimental
      study.
AB  - AIMS AND OBJECTIVES: To compare the effectiveness of clinical pathway-directed
      care to usual care on hospitalisation-related outcomes in patients with severe
      traumatic brain injury (STBI). BACKGROUND: Severe traumatic brain injury is a
      major cause of disability and mortality in young adults. Clinical pathways
      endeavour to bring evidence and clinical practice closer together to foster the
      delivery of best practice and to improve patient outcomes. DESIGN: Quasi
      experimental study. METHODS: The study was conducted in a trauma intensive care
      unit of a large teaching hospital in Egypt. Patients aged 18-60 years with a
      diagnosis of STBI, a Glasgow Coma Scale score between 3-8 and a nonpenetrating
      head injury were consecutively assigned to 15 days of care. The outcomes assessed
      were complications related to hospitalisation, clinical variances, length of
      intensive care unit (ICU) stay, ICU readmission rate and patient/family
      satisfaction. RESULTS: Sixty participants completed the study (30 in each arm).
      Apart from age, there were no significant differences between groups in baseline
      characteristics. The clinical pathway group demonstrated statistically
      significantly fewer cases of hospitalisation-related complications on day 15, and
      a significantly shorter length of ICU stay, lower ICU readmission rate and a high
      level of patient/family satisfaction when compared with the usual care group. The
      effect of the intervention on fever, pressure ulceration, hyperglycaemia and
      readmission to the ICU was no longer statistically significant after controlling
      for age. CONCLUSIONS: The findings of the current study suggest that the
      implementation of a clinical pathway for patients with severe TBI may be helpful
      in improving the patient experience as well as some hospitalisation-related
      outcomes. RELEVANCE TO CLINICAL PRACTICE: The provision of clinical pathway
      directed care in a trauma ICU may offer benefits to the patient, family and
      institution beyond that provided by usual care.

PMID- 29193517
TI  - Biological consequences of improving the structural stability of hairpins that
      have antimicrobial activity.
AB  - Designing new antimicrobial peptides (AMPs) focuses heavily on the activity of
      the peptide and less on the elements that stabilize the secondary structure of
      these peptides. Studies have shown that improving the structure of naturally
      occurring AMPs can affect activity and so here we explore the relationship
      between structure and activity of two non-naturally occurring AMPs. We have used
      a backbone-cyclized peptide as a template and designed an uncyclized analogue of
      this peptide that has antimicrobial activity. We focused on beta-hairpin-like
      structuring features. Improvements to the structure of this peptide reduced the
      activity of the peptide against gram-negative, Escherichia coli but improved the
      activity against gram-positive, Corynebacterium glutamicum. Distinctions in
      structuring effects on gram-negative versus gram-positive activity were also seen
      in a second peptide system. Structural improvements resulted in a peptide that
      was more active than the native against gram-positive bacterium but less active
      against gram-negative bacterium. Our results show that there is not always a
      correlation between improved hairpin-structuring and activity. Other factors such
      as the type of bacteria being targeted as well as net positive charge can play a
      role in the potency of AMPs. Copyright (c) 2017 European Peptide Society and John
      Wiley & Sons, Ltd.

PMID- 29193518
TI  - Antimicrobial activity of the indolicidin-derived novel synthetic peptide In-58.
AB  - Natural peptides with antimicrobial activity are extremely diverse, and peptide
      synthesis technologies make it possible to significantly improve their properties
      for specific tasks. Here, we investigate the biological properties of the natural
      peptide indolicidin and the indolicidin-derived novel synthetic peptide In-58. In
      58 was generated by replacing all tryptophan residues on phenylalanine in D
      configuration; the alpha-amino group in the main chain also was modified by
      unsaturated fatty acid. Compared with indolicidin, In-58 is more bactericidal,
      more resistant to proteinase K, and less toxic to mammalian cells. Using
      molecular physics approaches, we characterized the action of In-58 on bacterial
      cells at the cellular level. Also, we have found that studied peptides damage
      bacterial membranes. Using the Escherichia coli luminescent biosensor strain
      MG1655 (pcolD'::lux), we investigated the action of indolicidin and In-58 at the
      subcellular level. At subinhibitory concentrations, indolicidin and In-58 induced
      an SOS response. Our data suggest that indolicidin damages the DNA, but bacterial
      membrane perturbation is its principal mode of action. Copyright (c) 2017
      European Peptide Society and John Wiley & Sons, Ltd.

PMID- 29193519
TI  - Photoactivated N-Acyliminoiodinanes Applied to Amination: an ortho-Methoxymethyl
      Group Stabilizes Reactive Precursors.
AB  - N-Acyliminoiodinanes were characterized for the first time by X-ray structural
      analysis. The ortho-methoxymethyl group and the carbonyl oxygen coordinate to the
      iodine atom of the iminoiodinane. Activation of the N-acyliminoiodinane was
      achieved by photoirradiation at 370 nm, thereby enabling reaction with various
      silyl enol ethers to give alpha-aminoketone derivatives in good to high yield. N
      sulfonyliminoiodinanes bearing ortho substituents were used in photoinduced
      amination.

PMID- 29193520
TI  - Physiological significance of multipolar cells generated from neural stem cells
      and progenitors for the establishment of neocortical cytoarchitecture.
AB  - Neurogenesis encompasses an entire set of events that leads to the generation of
      newborn neurons from neural stem cells and more committed progenitor cells,
      including cell division, the production of migratory precursors and their
      progeny, differentiation and integration into circuits. In particular, the
      precise control of neuronal migration and morphological changes is essential for
      the development of the neocortex. Postmitotic cells within the intermediate zone
      have been found to transiently assume a characteristic "multipolar" morphology,
      after which a multipolar-to-bipolar transition occurs before the cells enter the
      cortical plate; however, the importance of this multipolar phase in the
      establishment of mature cortical cytoarchitecture and the precise genetic control
      of this phase remains largely unknown. Thus, this review article focuses on the
      multipolar phase in the developing neocortex. It begins by summarizing the
      molecular mechanism that underlies multipolar migration for the regulation of
      each step in multipolar phase in intermediate zone. The physiological
      significance of this multipolar phase in the establishment of mature cortical
      lamination and neurodevelopmental disorders associated with migration defects is
      then described.

PMID- 29193521
TI  - Assembly of insect hormone enthusiasts at Nasu Highland, Japan: Report of the 3rd
      International Insect Hormone (21st Ecdysone) Workshop.
AB  - The 3rd International Insect Hormone (21st Ecdysone) Workshop (IIHW2017) was held
      in July 2017 at Nasu Highland, Japan. In the 40 years of the workshop's history,
      this was the first to be held in an Asian country. A total of 109 insect hormone
      researchers from 18 countries (62 overseas and 47 domestic participants) attended
      IIHW2017. During the workshop, all participants stayed on-site at the venue's
      hotel; this was ideal for fostering communication between participants, in
      particular, interactions between principal investigators and young scientists.
      The workshop featured one keynote, 64 oral, and 35 poster presentations spanning
      molecular biology, cell biology, developmental biology, neurobiology, chemical
      biology, physiology, and ecology of insect hormones, including ecdysteroids,
      juvenile hormones, and a variety of neuropeptides. The workshop provided an ideal
      platform for discussing insect hormone biology using not only the typical genetic
      model insect, the fruit fly Drosophila, but also a diversity of interesting
      insects, such as the silkworm, the red flour beetle, the cricket, the dragonfly,
      the social ant, the bloodsucking tick, and so on. The participants succeeded in
      sharing the latest knowledge in a wide range of insect hormone research fields
      and in joining active and constructive scientific discussions.

PMID- 29193522
TI  - Carbonylative Coupling of Alkyl Zinc Reagents with Benzyl Bromides Catalyzed by a
      Nickel/NN2  Pincer Ligand Complex.
AB  - An efficient catalytic protocol for the three-component assembly of benzyl
      bromides, carbon monoxide, and alkyl zinc reagents to give benzyl alkyl ketones
      is described, and represents the first nickel-catalyzed carbonylative coupling of
      two sp3 -carbon fragments. The method, which relies on the application of nickel
      complexed with an NN2 -type pincer ligand and a controlled release of CO gas from
      a solid precursor, works well with a range of benzylic bromides. Mechanistic
      studies suggest the intermediacy of carbon-centered radicals.

PMID- 29193524
TI  - Effect of Site-Specific Peptide-Tag Labeling on the Biocatalytic Properties of
      Thermoalkalophilic Lipase from Geobacillus thermocatenulatus.
AB  - Tailor-made peptides were investigated for site-specific tag labeling of
      Geobacillus thermocatenulatus lipase (GTL). GTL was first genetically modified by
      introducing a unique cysteine on the lid site of the enzyme to produce two
      variants (GTLsigma-A193C and GTLsigma-S196C). Chemical modification was performed
      by using a small library of cysteine-containing peptides. The synthesized peptide
      lipase biocatalysts were highly stable, more active, more specific, and more
      selective toward different substrates than unmodified GTL. Very high enzyme
      thermostability of GTLsigma-A193C modified with peptides Ac-Cys-Phe-Gly-Phe-Gly
      Phe-CONH2 (1) and Ac-Cys-Phe-Phe-CONH2 (2) (>95 % activity after 24 h at 60 
      degrees C) was observed. The incorporation of 1 and 2 in GTLsigma-S196C improved
      its catalytic activity in the hydrolysis of p-nitrophenyl butyrate by factors of
      three and greater than five, respectively. The specificity for short-chain versus
      long-chain esters was also strongly improved. The diacylglycerol activity of
      GTLsigma-S196C was enhanced more than tenfold by the incorporation of 1 and more
      than threefold by modification of this variant with Ac-Cys-(Arg)7 -CONH2 (6) in
      the hydrolysis of 1-stearoyl-2-arachidonoyl-sn-glycerol. The enantioselectivity
      of GTLsigma-S196C increased for all formed bioconjugates, and the GTLsigma-S196C
      1 conjugate was the most active and selective in the hydrolysis of dimethylphenyl
      glutarate at pH 7 (72 % ee), also showing an inversion in the enzyme
      enantiopreference.

PMID- 29193525
TI  - Triple Bonds Between Iron and Heavier Group 15 Elements in AFe(CO)3- (A=As, Sb,
      Bi) Complexes.
AB  - Heteronuclear transition-metal-main-group-element carbonyl complexes of AsFe(CO)3
      , SbFe(CO)3- , and BiFe(CO)3- were produced by a laser vaporization supersonic
      ion source in the gas phase, and were studied by mass-selected IR
      photodissociation spectroscopy and advanced quantum chemistry methods. These
      complexes have C3v structures with all of the carbonyl ligands bonded on the iron
      center, and feature covalent triple bonds between bare Group 15 elements and
      Fe(CO)3- . Chemical bonding analyses on the whole series of AFe(CO)3- (A=N, P,
      As, Sb, Bi, Mc) complexes indicate that the valence orbitals involved in the
      triple bonds are hybridized 3d and 4p atomic orbitals of iron, leading to an
      unusual (dp-p) type of transition-metal-main-group-element multiple bonding. The
      sigma-type three-orbital interaction between Fe 3d/4p and Group 15 np valence
      orbitals plays an important role in the bonding and stability of the heavier
      AFe(CO)3- (A=As, Sb, Bi) complexes.

PMID- 29193523
TI  - Barriers to medication adherence and links to cardiovascular disease risk factor
      control: the Framingham Heart Study.
AB  - BACKGROUND: In the elderly, impaired cognition may weaken medication adherence
      and compromise treatment for cardiovascular disease (CVD). AIM: We examined risk
      factors for medication adherence and the relationship between adherence and
      levels of CVD risk factors among older participants with hypertension,
      dyslipidaemia and diabetes in the Framingham Heart Study. METHODS: The four-item
      Morisky Medication Adherence Scale was administered to 1559 participants, median
      age 70 years, 53% women. We created an adherence score, ranging from 0 to 4, with
      low adherence defined as a score >=2. CVD risk factors were assessed using
      standard protocols. Cognition was measured using the Mini-Mental State
      Examination (MMSE) and depressive symptoms were measured using the Center for
      Epidemiologic Studies of Depression (CES-D) scale. RESULTS: Among participants
      who self-reported taking antihypertensive, lipid-lowering and/or hyperglycaemic
      medication(s), 12% (n = 191) had low medication adherence. The risk of low
      adherence increased by 45% (95% confidence interval (CI): 25-68%, P < 0.001) per
      five-unit increase in CES-D score. In participants taking antihypertensive
      medication (n = 1017), low adherence was associated with higher mean diastolic
      blood pressure (73 mmHg, 95% CI: 71-75 vs 71 mmHg, 95% CI: 70-71; P = 0.04) after
      adjusting for covariates. Among participants taking lipid-lowering medication (n
      = 937), low adherence was associated with higher mean low-density lipoprotein
      cholesterol (92 mg/dL, 95% CI: 87-96 vs 86 mg/dL, 95% CI: 84-88; P = 0.03). Low
      adherence was not associated with fasting plasma glucose (P = 0.10) or
      haemoglobin A1c (P = 0.68) in the subgroup of participants (n = 192) taking
      hypoglycaemic medication. CONCLUSIONS: Depressive symptoms might act as a barrier
      for medication adherence, which exacerbates CVD risk factors in older-aged
      adults.

PMID- 29193526
TI  - Triple phase computed tomography of the pancreas in healthy cats.
AB  - While the availability and use of computed tomography (CT) continues to grow, no
      study has described the size and multiphase CT appearance of the normal feline
      pancreas. This information is important to not only allow more accurate
      identification and differentiation of disease, but it may also be useful in
      assessing pancreatic function. In this prospective analytical study, we described
      a triple phase CT protocol of the pancreas for use in sedated cats and the
      attenuation, enhancement pattern, size, and volume of the pancreas for a group of
      healthy cats. Fifteen healthy cats were enrolled in the study and a standardized
      protocol for acquiring arterial, portal, and delayed phase CT images of the
      pancreas was developed and described. The pancreas was hypo to isoattenuating to
      both the liver and spleen in all phases in the majority of cats with a homogenous
      enhancement pattern noted in all 15. Mean pancreatic attenuation was 48, 79, 166,
      and 126 Hounsfield units (HU) respectively on precontrast, arterial, portal, and
      delayed phase images. In addition, mean height, length, and width of the left
      lobe of the pancreas were larger than the right lobe in all 15 cats. There were
      no associations between volume and volume: body weight ratio with age (P =
      0.6518, P = 0.6968) or sex (P = 0.7013, P = 0.2043). This baseline information
      may be beneficial for use in future studies characterizing pancreatic disease in
      cats as well as future research studies evaluating pancreatic endocrine function.

PMID- 29193527
TI  - Telemedicine follow-up facilitates more comprehensive diabetes foot ulcer care: A
      qualitative study in home-based and specialist health care.
AB  - AIMS AND OBJECTIVES: To investigate the application of a telemedicine
      intervention in diabetes foot ulcer care, and its implications for the healthcare
      professionals in the clinical field. BACKGROUND: Contextual factors are found to
      be important when applying technology in health care and applying telemedicine in
      home-based care has been identified as particularly complex. DESIGN AND METHODS:
      We conducted field observations and individual interviews among healthcare
      professionals in home-based care and specialist health care in a diabetes foot
      care telemedicine RCT (Clin.Trial.gov: NCT01710774) during 2016. This study was
      guided by Interpretive Description, an inductive qualitative methodology.
      RESULTS: Overall, we identified unequal possibilities for applying telemedicine
      in diabetes foot ulcer care within the hospital and home care contexts. Different
      circumstances and possibilities in home-based care made the application of
      telemedicine as intended more difficult. The healthcare professionals in both
      care contexts perceived the application of telemedicine to facilitate a more
      comprehensive approach towards the patients, but with different possibilities to
      enact it. CONCLUSIONS: Application of telemedicine in home-based care was more
      challenging than in the outpatient clinic setting. Introducing more updated
      equipment and minor structural adjustments in consultation time and resources
      could make the use of telemedicine in home-based care more robust. RELEVANCE TO
      CLINICAL PRACTICE: Application of telemedicine in diabetes foot ulcer follow-up
      may enhance the nursing staff's ability to conduct comprehensive assessment and
      care of the foot ulcer as well as the patient's total situation. Access to
      adequate equipment and time, particularly in home-based care, is necessary to
      capitalise on this new technology.

PMID- 29193528
TI  - (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+
      and Ca2+ channels.
AB  - In this study, we aimed to investigate relaxant effect of flavanol (-)
      epicatechin on the isolated human saphenous vein (HSV), as a part of its
      cardioprotective action, and to define the mechanisms underlying this
      vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of
      HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine,
      margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while
      glibenclamide considerably reduced effects of the high concentrations of (-)
      epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM
      K+ , whereas in the presence of nifedipine produced partial relaxation of HSV
      rings pre-contracted by phenylephrine. In Ca2+ -free solution, (-)-epicatechin
      relaxed contraction induced by phenylephrine, but had no effect on contraction
      induced by caffeine. A sarcoplasmic reticulum Ca2+ -ATPase inhibitor,
      thapsigargin, significantly reduced relaxation of HSV produced by (-)
      epicatechin. These results demonstrate that (-)-epicatechin produces endothelium
      independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin
      probably involves activation of 4-aminopyridine- and margatoxin-sensitive KV
      channels, BKCa channels, and at least partly, KATP channels. In addition, not
      only the inhibition of extracellular Ca2+ influx, but regulation of the
      intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake
      into sarcoplasmic reticulum, via stimulation of Ca2+ -ATPase, as well, most
      likely participate in (-)-epicatechin-induced relaxation of HSV.

PMID- 29193529
TI  - Renal ultrasound and Doppler parameters as markers of renal function and
      histopathological damage in children with chronic kidney disease.
AB  - AIM: Doppler ultrasonography can be used to assess the progression of vascular
      (arterial sclerosis) and parenchymal (glomerular sclerosis and crescents) renal
      damage. The aim of this study was to evaluate the significance of some
      sonographic and Doppler parameters as non-invasive markers of glomerular
      filtration rate (GFR) and renal histopathological damage in children. METHODS: A
      cohort of 84 children were enrolled in a case-control study (42 with CKD stages 2
      5 and 42 healthy children). GFR was assessed using new improved equation using
      serum creatinine and cystatin C. Sonar guided renal specimen was obtained and
      evaluated for the severity of global sclerosis (GS), segmental sclerosis (SS),
      tubular atrophy (TA), interstitial fibrosis (IF), arterial sclerosis (AS) and
      arteriolar hyalinosis (AH). The following sonographic and Doppler parameters were
      assessed in both patients and control group: resistivity index (RI), pulsatility
      index (PI), atrophic index (AI), mean renal volume, mean renal density, time
      average velocity (TAV) and body surface area related volume perfusion (BSARVP).
      RESULTS: There was significant difference in renal density (P < 0.001), RI (P <
      0.001), PI (P = 0.021), TAV (P < 0.001) and BSARVP (P < 0.001) between patients
      and control group. The cutoff value of RI was 63.5% (sensitivity 83% and
      specificity 64%). Multivariate analysis revealed that renal density and RI were
      significant predictors of worsening of estimated GFR (eGFR) in CKD patients.
      CONCLUSION: Any increase in the RI and PI values must arouse alarm to the
      possibility of advancing renal damage. Moreover, RI and PI could fairly predict
      the degree of glomerular sclerosis and interstitial fibrosis.

PMID- 29193530
TI  - Shape-Controllable and Fluorescent Supramolecular Organic Frameworks Through
      Aqueous Host-Guest Complexation.
AB  - Two kinds of shape-controllable and fluorescent supramolecular organic frameworks
      (cuboid or spheroid) are constructed hierarchically from CB[8] and
      tetraphenylethylene derivatives through host-guest interaction in water. These
      two fluorescent SOFs exhibit intriguing and varied photophysical properties,
      including large red-shifts (up to 82 nm) and stimuli-responsive behavior to
      competitive guest by binding with CB[8], the turn-on fluorescence of which is
      applied in cellular imaging.

PMID- 29193531
TI  - High-voltage electrical injury: Modified surgical technique for optimal defect
      closuring of extra-large cranial defect.
AB  - Electrical burns are group of traumatic injuries with a mortality rate of 3-15%.
      High-voltage induced extensive electric burns are rarely seen in the cranial
      area, compared to upper and lower limbs, but extremely difficult for treatment,
      due to the limited flexibility in this area. The spectrum of therapeutic
      interventions in electrical burns in general, evolving initial necrectomy,
      decompression, and aggressive debridement with early skin coverage is usually not
      enough in cases of extensive cranial defects. The performance of a suitable flap
      combined with skin graft in donor site, and further implantation of expander is
      challenging in this area. We present a case of a high-voltage induced extra-large
      cranial injury in a 38-year-old man, treated with modified single large rotation
      flap and a split skin-thickness graft technique, for optimal defect closuring
      with satisfied aesthetic result.

PMID- 29193532
TI  - Future orientation in adolescent and young adult cancer survivors and unaffected
      peers.

PMID- 29193533
TI  - Living conditions and change in age of menarche in adult Maya mothers and
      daughters from Yucatan, Mexico.
AB  - OBJECTIVES: To analyze whether living conditions, experienced by mothers and
      adult daughters during their childhood, are associated with age at menarche (AAM)
      in daughters. METHODS: From September, 2011, to January, 2014, AAM and childhood
      living conditions were collected from a sample of 246 dyads of Maya mothers (mean
      age = 59.60 years, SD = 8.64) and their adult daughters (mean age = 33.03 years,
      SD = 5.57) from the cities of Merida and Motul in Yucatan, Mexico. Indicators of
      childhood living conditions were number of siblings and quality of house
      construction materials in both generations, and father's absence among daughters
      in their pre-menarcheal years. Multiple regression models were used to assess the
      association between childhood conditions in mother-daughter dyads and daughter's
      AAM. RESULTS: The recalled mean AAM of adult Maya daughters was 12.05 years (SD =
      1.53). After adjusting for the influence of mothers' AAM, number of siblings in
      both the mothers' and daughters' families directly predicted daughters' AAM (more
      siblings was associated with a later AAM); and a higher (better) index of
      household conditions in mothers' childhood was associated with earlier AAM in
      daughters. The household conditions index during the childhood of daughters and
      father's absence were not associated with their AAM. CONCLUSIONS: Our results
      suggest that better living conditions experienced by the mothers and daughters
      during their childhood may lower mean AAM in daughters in the context of
      populations that show important intergenerational changes in their social and
      economic conditions.

PMID- 29193534
TI  - DMSO as a mobile phase additive enhances detection of ubiquitination sites by
      nano-LC-ESI-MS/MS.
AB  - Large-scale detection of ubiquitination sites in whole cell proteomes using nano
      liquid chromatography coupled to tandem mass spectrometry is a well-established
      technique that has deepened the understanding of protein degradation processes in
      eukaryotic cells. Ubiquitination sites are usually identified by detection of Lys
      E-Gly-Gly (K-E-GG)-remnant peptides, which are generated by tryptic digestion of
      proteomes. We show in this application note that dimethyl sulfoxide addition to
      the liquid chromatography mobile phase enhances identification rates of K-E-GG
      peptides by more than 100% due to an increase of peptide signal intensities. The
      gain in the number of ubiquitination site identifications exceeds by far the gain
      that has been published for other posttranslational modifications, namely,
      phosphorylation and acetylation.

PMID- 29193535
TI  - Monodisperse N-Doped Graphene Nanoribbons Reaching 7.7 Nanometers in Length.
AB  - The properties of graphene nanoribbons are highly dependent on structural
      variables such as width, length, edge structure, and heteroatom doping.
      Therefore, atomic precision over all these variables is necessary for
      establishing their fundamental properties and exploring their potential
      applications. An iterative approach is presented that assembles a small and
      carefully designed molecular building block into monodisperse N-doped graphene
      nanoribbons with different lengths. To showcase this approach, the synthesis and
      characterisation of a series of nanoribbons constituted of 10, 20 and 30
      conjugated linearly-fused rings (2.9, 5.3, and 7.7 nm in length, respectively) is
      presented.

PMID- 29193536
TI  - Temporal trend and risk determinants of hepatocellular carcinoma in chronic
      hepatitis B patients on entecavir or tenofovir.
AB  - This study aimed to elucidate the temporal change and determinants for the risk
      of HCC in patients with chronic hepatitis B continuously receiving NUC. Through
      analysis of the national healthcare database in Taiwan, we screened a total of 65
      426 infected patients receiving entecavir or tenofovir for at least 3 months and
      excluded those with lamivudine, adefovir or telbivudine exposure, malignancy, end
      stage renal failure or a diagnosis of HCC within 3 months of starting treatment.
      Eligible patients (N = 27 820) were followed until HCC occurrence, completion of
      the allowed 3-year regimen or 31 December 2013. During a median follow-up of 25.1
      (12.1-35.6) months, 802 patients developed HCC, with 1-, 2- and 3-year cumulative
      incidence of 1.82% (95% CI, 1.66-1.99%), 3.05% (95% CI, 2.82-3.28%) and 4.06%
      (95% CI, 3.77-4.36%), respectively. HCC annual incidence decreased with an
      adjusted IRR of 0.73 (95% CI, 0.66-0.80) per yearly interval and was associated
      with cirrhosis (IRR, 10.07; 95% CI, 6.00-16.90 in age <40 years; 4.69; 95% CI,
      3.94-5.59 in age ?40 years), age (IRR, 3.38; 95% CI, 2.10-5.47 for 40-50 years;
      6.92; 95% CI, 4.27-11.21 for 50-60 years; 12.50; 95% CI, 7.71-20.25 for ?60
      years; <40 years as reference), male sex (IRR, 1.71; 95% CI, 1.44-2.04), HCV
      coinfection (IRR, 1.27; 95% CI, 1.02-1.58) and diabetes (IRR, 1.24; 95% CI, 1.05
      1.45). In conclusion, the risk of HCC in patients with chronic hepatitis B
      receiving entecavir or tenofovir declines over time and is determined by
      cirrhosis, age, male sex, HCV coinfection and diabetes.

PMID- 29193537
TI  - E-cigarette price sensitivity among middle- and high-school students: evidence
      from monitoring the future.
AB  - AIMS: We estimated associations between e-cigarette prices (both disposable and
      refill) and e-cigarette use among middle and high-school students in the United
      States. We also estimated associations between cigarette prices and e-cigarette
      use. DESIGN: We used regression models to estimate the associations between e
      cigarette and cigarette prices and e-cigarette use. In our regression models, we
      exploited changes in e-cigarette and cigarette prices across four periods of time
      and across 50 markets. We report the associations as price elasticities. In our
      primary model, we controlled for socio-demographic characteristics, cigarette
      prices, tobacco control policies, market fixed effects and year-quarter fixed
      effects. SETTING: United States of America. PARTICIPANTS: A total of 24 370
      middle- and high-school students participating in the Monitoring the Future
      Survey in years 2014 and 2015. MEASUREMENTS: Self-reported e-cigarette use over
      the last 30 days. Average quarterly cigarette prices, e-cigarette disposable
      prices and e-cigarette refill prices were constructed from Nielsen retail data
      (inclusive of excise taxes) for 50 US markets. FINDINGS: In a model with market
      fixed effects, we estimated that a 10% increase in e-cigarette disposable prices
      is associated with a reduction in the number of days vaping among e-cigarette
      users by approximately 9.7% [95% confidence interval (CI) = -17.7 to 1.8%; P =
      0.02] and is associated with a reduction in the number of days vaping by the full
      sample by approximately 17.9% (95% CI = -31.5 to -4.2%; P = 0.01). Refill e
      cigarette prices were not statistically significant predictors of vaping.
      Cigarette prices were not associated significantly with e-cigarette use
      regardless of the e-cigarette price used. However, in a model without market
      fixed effects, cigarette prices were a statistically significant positive
      predictor of total e-cigarette use. CONCLUSIONS: Higher e-cigarette disposable
      prices appear to be associated with reduced e-cigarette use among adolescents in
      the US.

PMID- 29193538
TI  - Diversity of Polyketide Chains Achieved by Deleting the Tailoring Genes in the
      Biosynthesis of Ansatrienins.
AB  - The ast gene cluster (GenBank accession numbers KF813023.1 and KP284551) was
      characterized to be responsible for the biosynthesis of ansatrienins in
      Streptomyces sp. XZQH13, which contains astC, astF1, and astF2 genes involved in
      the assembly of the N-cyclohexanoyl d-alanyl side chain and the hydroxylation of
      C-19, respectively. Further to investigating the biosynthetic mechanism of
      ansatrienins, herein we constructed the mutant strains XZQH13OEDeltaastF2 and
      XZQH13OEDeltaastCDeltaastF2. Three new ansatrienin analogues, namely,
      ansatrienols I-K (1-3), along with trienomycinol (4) and 3-O
      demethyltrienomycinol (5), were isolated from the XZQH13OEDeltaastCDeltaastF2
      strain, and trienomycin A (6) and trienomycin G (7) were isolated from the
      XZQH13OEDeltaastF2 strain. Their structures were determined by a combination of
      high-resolution MS (ESI) and 1D and 2D NMR spectroscopy. Accordingly, a pathway
      for the biosynthesis of these new ansatrienins was proposed.

PMID- 29193539
TI  - Comprehensive evaluation of the role of soy and isoflavone supplementation in
      humans and animals over the past two decades.
AB  - Soy and soy-based foods are considered healthy, particularly in many Asia-Pacific
      countries, where soy products have long been consumed. Soy and soy-related
      products have been found to help prevent the occurrence of cardiovascular
      diseases and certain types of cancer, such as breast and prostate cancer. These
      products can also have antioxidative effects that alleviate hot flashes during
      menopause and bone loss. These biological and therapeutic functions are primarily
      due to the isoflavones derived from soy, whose structure is similar to the
      structure of 17-beta-oestradiol. Despite the many health benefits for humans and
      animals, the application of isoflavones remains controversial because of their
      anti-oestrogenic properties. We focused on general information regarding
      isoflavones, as well as their structure, function, and application. We summarized
      evidence showing that dietary or supplemental isoflavones exert protective
      effects on the health of humans and animals. Based on the literature, we conclude
      that soy foods and isoflavones may be effective and safe; however, more high
      quality trials are needed to fully substantiate their potential use.

PMID- 29193540
TI  - The proportion of familial cases of type 1 diabetes is increasing simultaneously
      with the disease incidence: Eighteen years of the Israeli Pediatric Diabetes
      Registry.
AB  - BACKGROUND: The global rise in incidence of type 1 diabetes (T1D) is too rapid to
      be attributed to susceptible genetic background, pinpointing a significant role
      for environmental factors. Unlike the theory that the need for genetic
      susceptibility has lessened over time, we hypothesized that the rise in T1D
      incidence is faster in a genetically susceptible population. SUBJECTS AND
      METHODS: The study population comprised of 5080 patients aged 0 to 17 years who
      were reported to the National Israel Diabetes Registry between 1997 and 2014. The
      patients were divided into familial cases (first-degree relative has T1D), and
      sporadic cases. Demographic and clinical data were retrieved from the registry.
      The change in annual percent (from the entire cohort) was computed separately for
      the sporadic and familial cohorts. RESULTS: The familial (n = 546; 10.7%) and
      sporadic (n = 4534; 89.3%) cases were comparable for gender, ethnicity, and age
      at diagnosis. Consanguinity was more common in the familial vs sporadic group
      (10% vs 6.1%; P = .001). The average annual percent change increased by 1.9% in
      the familial cases and decreased by 0.2% in the sporadic cases (P = .04).
      CONCLUSIONS: The rapid rise in the proportion of familial cases of T1D suggests
      that environmental factors impose higher diabetogenic pressure in patients with a
      susceptible genetic background.

PMID- 29193541
TI  - Nitrogen use efficiency is regulated by interacting proteins relevant to
      development in wheat.
AB  - Wheat (Triticum aestivum) has low nitrogen use efficiency (NUE). The genetic
      mechanisms controlling NUE are unknown. Positional cloning of a major
      quantitative trait locus for N-related agronomic traits showed that the
      vernalization gene TaVRN-A1 was tightly linked with TaNUE1, the gene shown to
      influence NUE in wheat. Because of an Ala180 /Val180 substitution, TaVRN-A1a and
      TaVRN-A1b proteins interact differentially with TaANR1, a protein encoded by a
      wheat orthologue of Arabidopsis nitrate regulated 1 (ANR1). The transcripts of
      both TaVRN-A1 and TaANR1 were down-regulated by nitrogen. TaANR1 was functionally
      characterized in TaANR1::RNAi transgenic wheat, and in a natural mutant with a 23
      bp deletion including 10-bp at the 5' end of intron 5 and 13-bp of exon 6 in gDNA
      sequence in its gDNA sequence, which produced transcript that lacked the full 84
      bp exon 6. Both TaANR1 and TaHOX1 bound to the Ala180 /Val180 position of TaVRN
      A1. Genetically incorporating favourable alleles from TaVRN-A1, TaANR1 and TaHOX1
      increased grain yield from 9.84% to 11.58% in the field. Molecular markers for
      allelic variation of the genes that regulate nitrogen can be used in breeding
      programmes aimed at improving NUE and yield in novel wheat cultivars.

PMID- 29193542
TI  - Improved performance of quantitative collagen parameters versus standard
      histology in longitudinal assessment of nonadvanced liver fibrosis for chronic
      hepatitis B.
AB  - Monitoring longitudinal nonadvanced fibrosis is a more common scenario in
      management of chronic hepatitis B (CHB), for which, however, current evaluation
      methods generally lack sufficient performance. We conducted a proof-of-concept
      study to evaluate the performance of quantitative fibrous collagen parameters (q
      FP) in the assessment. Data sets from a prior CHB trial (NCT00962533) with mostly
      mild-to-moderate fibrosis participants were used for this study. 301 subjects
      with paired liver biopsies were consecutively included. Of these, 139 subjects
      were used to establish the test and the rest for internal validation. Fibrosis
      change between baseline and week 104 of treatment was blindly assessed with q-FP
      and was compared with Ishak fibrosis staging. There were 70% and 93% subjects
      with Ishak F0-2 at baseline and week 104, respectively. For the test of the
      subjects, q-FP and Ishak staging showed no difference in determining the
      incidence of fibrosis regression (68% vs 67%; difference = 0.7%, P = 1.00). Q-FP
      demonstrated that the regression was independently associated with the antiviral
      efficacy endpoint (OR 3.0, 95% CI 1.4-6.5, P = .005), but Ishak failed the
      detection (OR 0.6, 95% CI 0.3-1.3, P = .24). Moreover, q-FP directly revealed a
      higher fibrosis-resistance to antiviral treatment in virus genotypes C vs B and
      in males vs females. These results were confirmed in the validation subjects.
      Additionally, a functional model built on the test subjects showed an accuracy of
      82% in stratifying fibrosis reversibility of the validation subjects. In
      conclusion, q-FP could have improved efficiency and accuracy in the longitudinal
      assessment of mild-to-moderate CHB fibrosis, indicating a potential alternative
      to current evaluation methodologies.

PMID- 29193543
TI  - Initiation of dapagliflozin and treatment-emergent fractures.
AB  - An increase in fracture risk has been reported in patients with type 2 diabetes
      mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced
      by all members of the sodium-glucose co-transporter-2 (SGLT2) inhibitor class. It
      is unclear whether initiation of dapagliflozin is followed by an increase in the
      risk of fracture; therefore, we performed a population-based, open cohort study
      (from January 2013 to January 2016) using The Health Improvement Network (THIN).
      A total of 22 618 people with T2DM (4548 exposed to dapagliflozin and 18 070
      receiving standard antidiabetic treatment, matched for age, sex, body mass index
      and diabetes duration) with no history of fractures at baseline were included.
      The primary outcome was the occurrence of any fragility fracture (hip, spine,
      wrist) during the observation period. Risk of any fracture served as a secondary
      outcome. Adjusted hazard rate ratios (HRs) with 95% confidence intervals (CIs)
      were calculated using Cox regression. A total of 289 fractures (132 fragility
      fractures) were recorded. No difference in the risk of fragility fracture was
      detected between participants prescribed dapagliflozin and matched control
      participants (crude HR 0.90, 95% CI 0.59-1.39, P = .645; adjusted HR 0.87, 95% CI
      0.56-1.35, P = .531). Similarly, no difference in the risk of any fracture was
      detected (adjusted HR 0.89, 95% CI 0.66-1.20; P = .427). Sensitivity analyses
      limited to the subset of the population at high risk of fracture produced similar
      results; thus, there was no evidence to suggest an increase in the risk of
      treatment-emergent fractures in patients with T2DM who initiated treatment with
      dapagliflozin.

PMID- 29193544
TI  - Characterisation of a Bacterial Galactokinase with High Activity and Broad
      Substrate Tolerance for Chemoenzymatic Synthesis of 6-Aminogalactose-1-Phosphate
      and Analogues.
AB  - Glycosyl phosphates are important intermediates in many metabolic pathways and
      are substrates for diverse carbohydrate-active enzymes. Thus, there is a need to
      develop libraries of structurally similar analogues that can be used as selective
      chemical probes in glycomics. Here, we explore chemoenzymatic cascades for the
      fast generation of glycosyl phosphate libraries without protecting-group
      strategies. The key enzyme is a new bacterial galactokinase (LgGalK) cloned from
      Leminorella grimontii, which was produced in Escherichia coli and shown to
      catalyse 1-phosphorylation of galactose. LgGalK displayed a broad substrate
      tolerance, being able to catalyse the 1-phosphorylation of a number of galactose
      analogues, including 3-deoxy-3-fluorogalactose and 4-deoxy-4-fluorogalactose,
      which were first reported to be substrates for wild-type galactokinase. LgGalK
      and galactose oxidase variant M1 were combined in a one-pot, two-step system to
      synthesise 6-oxogalactose-1-phosphate and 6-oxo-2-fluorogalactose-1-phosphate,
      which were subsequently used to produce a panel of 30 substituted 6
      aminogalactose-1-phosphate derivatives by chemical reductive amination in a one
      pot, three-step chemoenzymatic process.

PMID- 29193545
TI  - Identification and Characterization of a Single High-Affinity Fatty Acid Binding
      Site in Human Serum Albumin.
AB  - A single high-affinity fatty acid binding site in the important human transport
      protein serum albumin (HSA) is identified and characterized using an NBD (7
      nitrobenz-2-oxa-1,3-diazol-4-yl)-C12 fatty acid. This ligand exhibits a 1:1
      binding stoichiometry in its HSA complex with high site-specificity. The complex
      dissociation constant is determined by titration experiments as well as
      radioactive equilibrium dialysis. Competition experiments with the known HSA
      binding drugs warfarin and ibuprofen confirm the new binding site to be different
      from Sudlow-sites I and II. These binding studies are extended to other albumin
      binders and fatty acid derivatives. Furthermore an X-ray crystal structure allows
      locating the binding site in HSA subdomain IIA. The knowledge about this novel
      HSA site will be important for drug depot development and for understanding drug
      protein interaction, which are important prerequisites for modulation of drug
      pharmacokinetics.

PMID- 29193546
TI  - Relationship between high-risk patients receiving prescription opioids and high
      volume opioid prescribers.
AB  - AIMS: (1) To characterize the amount of prescription opioids prescribed for high
      risk patients by low-volume prescribers; (2) to quantify how high- and low-volume
      prescribers differ systematically in their prescribing patterns. DESIGN: Cross
      sectional study using 2015 longitudinal, all-payer QuintilesIMS pharmacy claims.
      We conducted an aggregated analysis for the first aim and an individual-level
      analysis for the second aim. SETTING: California, Florida, Georgia, Maryland, and
      Washington, USA. PARTICIPANTS: Among 4 046 275 patients, we identified 375 848
      concomitant users (filling more than 30-days of concomitant opioids and
      benzodiazepines), 150 814 chronic users (using 100+ morphine milligram
      equivalents (MMEs) per day for more than 90 days), and 3190 patients prescribed
      opioids by > 3 prescribers and filling opioids at > 3 pharmacies during any 90
      day period. Among 192 126 prescribers, we identified 8023 high-volume
      prescribers, who comprised the highest fifth percentile of opioid volume during
      four calendar quarters. MEASUREMENTS: (1) MME dose per transaction, (2) days
      supplied per transaction, (3) total opioid volume per patient and (4) number of
      prescriptions per patient. We also examined differences in opioid dispensing
      between high- and low-volume prescribers among patients receiving opioids from
      both. FINDINGS: Low-volume prescribers accounted for 15-29% of opioid volume and
      18-56% of opioid prescriptions for high-risk patients, compared with 28-37% and
      53-58% for low-risk patients. After accounting for state of residence, comorbid
      burden, prescriber specialty and care sequence, patients were more likely to
      receive higher doses (60.9 versus 53.2 MMEs per day, P < 0.01), longer supplies
      (22.1 versus 15.6 days, P < 0.01), more prescriptions (4.0 versus 2.6
      prescriptions, P < 0.01) and greater opioid volume (5.6 versus 1.9 g, P < 0.01)
      from high- than low-volume prescribers. CONCLUSIONS: In the United States, high
      risk patients obtain a substantial proportion of prescription opioids from low
      volume prescribers. The differences in prescribing patterns between high- and low
      volume prescribers suggest the importance of interventions targeting prescriber
      behaviors.

PMID- 29193547
TI  - Safety and efficacy of telbivudine in late pregnancy to prevent mother-to-child
      transmission of hepatitis B virus: A multicenter prospective cohort study.
AB  - Infection of hepatitis B virus (HBV) occurs in ~10% of infants of HBV-infected
      mothers with positive hepatitis B e antigen (HBeAg) after immunoprophylaxis. We
      aimed to evaluate the safety and efficacy of telbivudine used during late
      pregnancy for preventing mother-to-child transmission of HBV. We conducted a
      multicenter prospective cohort study in 5 hospitals from 2012 to 2014, which
      enrolled HBV-infected singleton pregnant women with positive HBeAg. By their
      choice, women were divided into therapy (telbivudine 600 mg/day, from gestation
      28-32 weeks to 3-4 weeks postpartum) and control (no antiviral agent) groups.
      Infants received passive-active immunoprophylaxis and follow-up at the age of 7
      14 months. Totally, 328 pregnant women were included: 149 in the telbivudine
      group and 179 in the control group. Baseline HBV DNA levels were similar in the 2
      groups (7.43 vs 7.37 log10 IU/mL, P = .711). At delivery, HBV DNA levels in the
      telbivudine and control groups were 3.80 and 7.26 log10 IU/mL, respectively (P <
      .0001). Of the infants, 128 (85.9%) in the telbivudine group and 156 (87.2%) in
      the control group were followed up. No infant in the telbivudine group had
      chronic infection, while 2 (1.28%) infants in the control group did (P = .503).
      Three (2.34%) infants in the telbivudine group, but none in the control group,
      had severe congenital or developmental abnormalities (P = .090). The data
      indicate that telbivudine may block perinatal HBV transmission. However, larger
      studies are required to clarify whether anti-HBV therapy in pregnancy is
      associated with severe adverse effects in the foetuses and infants.

PMID- 29193548
TI  - RePHILL: protocol for a randomised controlled trial of pre-hospital blood product
      resuscitation for trauma.
AB  - OBJECTIVES: To describe the 'Resuscitation with Pre-HospItaL bLood products'
      trial (RePHILL) - a multi-centre randomised controlled trial of pre-hospital
      blood product (PHBP) administration vs standard care for traumatic haemorrhage.
      BACKGROUND: PHBP are increasingly used for pre-hospital trauma resuscitation
      despite a lack of robust evidence demonstrating superiority over crystalloids.
      Provision of PHBP carries additional logistical and regulatory implications, and
      requires a sustainable supply of universal blood components. METHODS: RePHILL is
      a multi-centre, two-arm, parallel group, open-label, phase III randomised
      controlled trial currently underway in the UK. Patients attended by a pre
      hospital emergency medical team, with traumatic injury and hypotension (systolic
      blood pressure <90 mmHg or absent radial pulse) believed to be due to traumatic
      haemorrhage are eligible. Exclusion criteria include age <16 years, blood product
      receipt on scene prior to randomisation, Advanced Medical Directive forbidding
      blood product administration, pregnancy, isolated head injury and prisoners. A
      total of 490 patients will be recruited in a 1 : 1 ratio to receive either the
      intervention (up to two units of red blood cells and two units of lyophilised
      plasma) or the control (up to four boluses of 250 mL 0.9% saline). The primary
      outcome measure is a composite of failure to achieve lactate clearance of >=20%/h
      over the first 2 hours after randomisation and all-cause mortality between
      recruitment and discharge from the primary receiving facility to non-acute care.
      Secondary outcomes include pre-hospital time, coagulation indices, in-hospital
      transfusion requirements and morbidity. RESULTS: Pilot study recruitment began in
      December 2016. Approval to proceed to the main trial was received in June 2017.
      Recruitment is expected to continue until 2020. CONCLUSIONS: RePHILL will provide
      high-quality evidence regarding the efficacy and safety of PHBP resuscitation for
      trauma.

PMID- 29193549
TI  - Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.
AB  - We estimated the total number of undiagnosed HBV and HCV carriers and patients
      with hepatitis virus-related disease in Japan according to 6 different groups
      classified by their natural histories during 2011. In 2011, the total number of
      carriers and patients infected with HBV or HCV was estimated according to 6
      groups using government reports and reports from the hepatitis epidemiology
      research group of The Ministry of Health, Labor and Welfare in Japan. In 2011,
      the total number of hepatitis virus carriers was estimated to be 2 090 128-2 840
      128 in which the estimated number of undiagnosed HCV and HBV carriers was 776 826
      (HBV: 481 470; HCV: 295 356). The total number of treated patients, as either
      inpatients or outpatients, was estimated to be 811588 (HBV: 303 366; HCV: 520
      600) in 2011. It is presumed that many carriers shirk consultation for many
      reasons, such as patients' misunderstanding, lack of awareness and forgetfulness
      of their positive status. The numbers of infected patients who did not seek
      treatment increased gradually to 501 714-1 251 714 (HBV: 333 791-483 791; HCV:
      167 923-767 923) in 2011. Compared to 2000, the number of undiagnosed carriers
      was significantly reduced in 2011 probably because of the well-organized,
      effective national hepatitis virus screening system that has been launched by the
      Japanese government since 2002. Moreover, the increase in the number of untreated
      persons who are aware of their positive status shows that more effort should be
      invested in improving the referral system from screening centres to core
      hospitals.

PMID- 29193550
TI  - Loss of dendritic connectivity in southern California's urban riverscape
      facilitates decline of an endemic freshwater fish.
AB  - Life history adaptations and spatial configuration of metapopulation networks
      allow certain species to persist in extreme fluctuating environments, yet long
      term stability within these systems relies on the maintenance of linkage habitat.
      Degradation of such linkages in urban riverscapes can disrupt this dynamic in
      aquatic species, leading to increased extinction debt in local populations
      experiencing environment-related demographic flux. We used microsatellites and
      mtDNA to examine the effects of collapsed network structure in the endemic Santa
      Ana sucker Catostomus santaanae of southern California, a threatened species
      affected by natural flood-drought cycles, "boom-and-bust" demography,
      hybridization and presumed artificial transplantation. Our results show a
      predominance of drift-mediated processes in shaping population structure and that
      reverse mechanisms for counterbalancing the genetic effects of these phenomena
      have dissipated with the collapse of dendritic connectivity. We use approximate
      Bayesian models to support two cases of artificial transplantation and provide
      evidence that one of the invaded systems better represents the historic processes
      that maintained genetic variation within watersheds than any remaining drainages
      where C. santaanae is considered native. We further show that a stable dry gap in
      the northern range is preventing genetic dilution of pure C. santaanae persisting
      upstream of a hybrid assemblage involving a non-native sucker and that local
      accumulation of genetic variation in the same drainage is influenced by position
      within the network. This work has important implications for declining species
      that have historically relied on dendritic metapopulation networks to maintain
      source-sink dynamics in phasic environments, but no longer possess this capacity
      in urban-converted landscapes.

PMID- 29193552
TI  - Live-Cell Protein Sulfonylation Based on Proximity-driven N-Sulfonyl Pyridone
      Chemistry.
AB  - The development of bioorthogonal approaches for labeling of endogenous proteins
      under the multimolecular crowding conditions of live cells is highly desirable
      for the analysis and engineering of proteins without using genetic manipulation.
      N-Sulfonyl pyridone (SP) is reported as a new reactive group for protein
      sulfonylation. The ligand-directed SP chemistry was able to modify not only
      purified proteins in vitro, but also endogenous ones on the surface of and inside
      live cells selectively and rapidly, which allowed to convert endogenous proteins
      to FRET-based biosensors in situ.

PMID- 29193551
TI  - The microbial community of a biofilm contact reactor for the treatment of winery
      wastewater.
AB  - AIMS: To utilize a three-tiered approach to provide insight into the microbial
      community structure, the spatial distribution and the metabolic capabilities of
      organisms of a biofilm in the two towers of a high-rate biological contact
      reactor treating winery wastewater. METHODS AND RESULTS: Next-generation
      sequencing indicated that bacteria primarily responsible for the removal of
      carbohydrates, sugars and alcohol were more abundant in tower 1 than tower 2
      while nitrifying and denitrifying bacteria were more abundant in tower 2. Yeast
      populations differed in each tower. Fluorescent in situ hybridization coupled
      with confocal microscopy showed distribution of organisms confirming an oxygen
      gradient across the biofilm depth. The Biolog system (ECO plates) specified the
      different carbon-metabolizing profiles of the two biofilms. CONCLUSIONS: The
      three-tiered approach confirmed that the addition of a second subunit to the
      bioreactor, expanded the treatment capacity by augmenting the microbial and
      metabolic diversity of the system, improving the treatment scope of the system.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A three-tiered biofilm analysis provided
      data required to optimize the design of a bioreactor to provide favourable
      conditions for the development of a microbial consortium, which has optimal waste
      removal properties for the treatment requirements at hand.

PMID- 29193553
TI  - Styling without shedding: Novel topical formula reduces hair shedding by
      contracting the arrector pili muscle.
AB  - Approximately 40% of women experience excessive hair shedding during styling
      (e.g., hair brushing). Previously, we demonstrated that topically applied
      phenylephrine, a potent alpha1 adrenergic receptor agonist, can be used to
      contract the arrector pili muscle of the follicular unit; thus, increasing the
      force required to pluck hair and reducing shedding during brushing. While
      demonstrating efficacy, phenylephrine has several drawbacks when applied to the
      scalp, including the possibility cardiovascular events. We hypothesized that a
      high concentration of a weak alpha1 agonist would allow for: (a) rapid
      penetration through the stratum corneum eliciting a quick response; (b) a low
      probability of cardiac adverse events owing to the low receptor binding affinity;
      and (c) an efficacy of the weak alpha1 agonist similar to that of phenylephrine
      at the local site of application. Accordingly, we developed a novel topical
      solution, AB-102, containing a high concentration of a weak alpha1 agonist.
      Several studies were conducted to test the safety and efficacy of AB-102. In a
      dose escalating safety study, utilizing a wearable holter monitor, we observed no
      cardiac or hemodynamic adverse events. In addition, in a controlled efficacy
      study, AB-102 reduced the number of hairs shed during brushing by up to 77%
      (average of 38%).

PMID- 29193554
TI  - Do delays in data availability limit the implementation of near real-time vaccine
      safety surveillance using the Clinical Practice Research Datalink?
AB  - PURPOSE: Near real-time vaccine safety surveillance (NRTVSS) using electronic
      health records has been used to detect timely vaccine safety signals. Trial
      implementation of NRTVSS using the Clinical Practice Research Datalink (CPRD) has
      shown that there is limited power to detect safety signals for rare events.
      Delays in recording outcomes and receiving data influence the power and
      timeliness to identify a signal. Our work aimed to compare how different sources
      of delays influence power and expected time to signal to implement NRTVSS using
      CPRD. METHODS: We studied seasonal influenza vaccine/Guillain-Barre syndrome and
      performed power and expected time to signal calculations for the 2013-2014/2014
      2015 seasons. We used the Poisson-based maximised sequential probability ratio
      test, which compares observed-to-expected events. For each study season, we
      obtained an average Guillain-Barre syndrome/seizures age-sex-adjusted rate from
      the 5 previous seasons and then used this rate to calculate the expected number
      of events, assuming a 42-day risk-window. Calculations were performed for
      detecting rate ratios of 1.5 to 10. We compared power and timeliness considering
      combinations of the presence/absence of delays in recording outcomes and in
      receiving data. The R-package Sequential was used. RESULTS: In general, there was
      >=80% power to detect increases in risk of >=4 at the end of the season. Assuming
      absence of delays slightly improved power (a maximum increase of 4%) but did not
      noticeably reduce time to detect a signal. CONCLUSION: Removing delays in data
      availability is insufficient to significantly improve the performance of a NRTVSS
      system using CPRD. Expansion of CPRD data is required. KEY POINTS The Clinical
      Practice Research Datalink (CPRD) can be used to implement near real-time vaccine
      safety surveillance, but there is limited power to detect signals for rare
      outcomes. Delays in recording outcomes and in receiving data might limit power
      and timeliness of a system. We assessed the influence of these sources of delays
      to inform data providers of the steps required to improve a system using CPRD
      data. Removing delays in recording outcomes and receiving data is unlikely to
      significantly improve the performance of a system using CPRD data. Expansion of
      the data available is needed.

PMID- 29193555
TI  - Overtreatment of older patients with type 2 diabetes mellitus in primary care.
AB  - Given that there are indications of overtreatment in older patients with type 2
      diabetes in both the United States and Europe, we assessed the level of
      personalized diabetes treatment for older patients in primary care, focusing on
      overtreatment. Based on Dutch guidelines individuals aged >=70 years were
      classified into 3 glycated haemoglobin (HbA1c) treatment target groups: 7% (53
      mmol/mol), 7.5% (58 mmol/mol) and 8% (64 mmol/mol). In our cohort of 1002
      patients (n = 319 aged >=70 years), the 165 patients with HbA1c targets >7% had
      more micro- and macrovascular complications, more often used >=5 medicines and
      were more often frail compared with those with an HbA1c target <=7%. Of these 165
      patients, 64 (38.8%) were overtreated; that is, 20% of all people aged >=70
      years. The majority of overtreated people were frail and used >=5 medicines.
      Hypoglycaemia occurred in 20.3% of these patients and almost 30% reported
      accidents involving falls. Personalized treatment in older people with type 2
      diabetes is not common practice. A substantial number of older people are
      overtreated, with probable harmful consequences. To prevent overtreatment,
      definition of lower HbA1c limits might be helpful.

PMID- 29193556
TI  - The Role of Copper Speciation in the Low Temperature Oxidative Upgrading of Short
      Chain Alkanes over Cu/ZSM-5 Catalysts.
AB  - Partial oxidative upgrading of C1 -C3 alkanes over Cu/ZSM-5 catalysts prepared by
      chemical vapour impregnation (CVI) has been studied. The undoped ZSM-5 support is
      itself able to catalyse selective oxidations, for example, methane to methanol,
      using mild reaction conditions and the green oxidant H2 O2 . Addition of Cu
      suppresses secondary oxidation reactions, affording methanol selectivities of up
      to 97 %. Characterisation studies attribute this ability to population of
      specific Cu sites below the level of total exchange (Cu/Al<0.5). These species
      also show activity for radical-based methane oxidation, with productivities
      exceeding those of the parent zeolite supports. When tested for ethane and
      propane oxidation reactions, comparable trends are observed.

PMID- 29193557
TI  - A three-goal model for patients with multimorbidity: A qualitative approach.
AB  - BACKGROUND: To meet the challenge of multimorbidity in decision making, a switch
      from a disease-oriented to a goal-oriented approach could be beneficial for
      patients and clinicians. More insight about the concept and the implementation of
      this approach in clinical practice is needed. OBJECTIVE: This study aimed to
      develop conceptual descriptions of goal-oriented care by examining the
      perspectives of general practitioners (GPs) and clinical geriatricians (CGs), and
      how the concept relates to collaborative communication and shared decision making
      with elderly patients with multimorbidity. METHOD: Qualitative interviews with
      GPs and CGs were conducted and analyzed using thematic analysis. RESULTS:
      Clinicians distinguished disease- or symptom-specific goals, functional goals and
      a new type of goals, which we labelled as fundamental goals. "Fundamental goals"
      are goals specifying patient's priorities in life, related to their values and
      core relationships. These fundamental goals can be considered implicitly or
      explicitly in decision making or can be ignored. Reasons to explicate goals are
      the potential mismatch between medical standards and patient preferences and the
      need to know individual patient values in case of multimorbidity, including the
      management in acute situations. CONCLUSION: Based on the perspectives of
      clinicians, we expanded the concept of goal-oriented care by identifying a three
      level goal hierarchy. This model could facilitate collaborative goal-setting for
      patients with multiple long-term conditions in clinical practice. Future research
      is needed to refine and validate this model and to provide specific guidance for
      medical training and practice.

PMID- 29193558
TI  - Short dental implants as compared to maxillary sinus augmentation procedure for
      the rehabilitation of edentulous posterior maxilla: Three-year results of a
      randomized clinical study.
AB  - BACKGROUND: Several treatment options exist for the implant-supported
      rehabilitation of edentulous posterior maxilla. PURPOSE: To compare maxillary
      sinus floor augmentation associated to standard length implants, with direct
      placement of implants of reduced length in the available residual bone. MATERIALS
      AND METHODS: Patients with edentulous posterior maxilla and a residual height of
      4-7 mm were randomly allocated to the test (short implants [SIs], 6.5 to 8.5mm
      long) or the control (sinus augmentation [SA] and implants >=10mm long) group.
      Anorganic bovine bone was the grafting material for the control group. In both
      groups pure platelet-rich plasma was used to bioactivate implant surface prior to
      insertion. Implant and prosthesis survival, clinical variables, radiographic bone
      level change, quality of life, and patient satisfaction were assessed. RESULTS:
      Twenty-five patients were treated in the control group (58 standard length
      implants) and 27 in the test group (42 SIs). After 3 years of follow-up no
      implant failure and biological or mechanical complications were recorded.
      Marginal bone loss, soft tissue, and oral hygiene parameters were similar in the
      2 groups at both 1 and 3 years' follow-up. Postoperative pain, swelling and other
      symptoms and daily activities were better in the SIs group than in the SA group,
      while patients' satisfaction after 1 year was similar. CONCLUSIONS: In spite of
      comparable medium-term clinical and radiographic outcomes, when the residual
      ridge height is sufficient for a safe placement, SIs may be preferred due to
      simplified protocol, less invasiveness, shorter treatment time, and reduced
      postoperative discomfort as compared to SA.

PMID- 29193559
TI  - Evaluation of exome filtering techniques for the analysis of clinically relevant
      genes.
AB  - A significant challenge facing clinical translation of exome sequencing is
      meaningful and efficient variant interpretation. Each exome contains ~500 rare
      coding variants; laboratories must systematically and efficiently identify which
      variant(s) contribute to the patient's phenotype. In silico filtering is an
      approach that reduces analysis time while decreasing the chances of incidental
      findings. We retrospectively assessed 55 solved exomes using available datasets
      as in silico filters: Online Mendelian Inheritance in Man (OMIM), Orphanet, Human
      Phenotype Ontology (HPO), and Radboudumc University Medical Center curated
      panels. We found that personalized panels produced using HPO terms for each
      patient had the highest success rate (100%), while producing considerably less
      variants to assess. HPO panels also captured multiple diagnoses in the same
      individual. We conclude that custom HPO-derived panels are an efficient and
      effective way to identify clinically relevant exome variants.

PMID- 29193560
TI  - Cobalt-Catalyzed Diborylation of 1,1-disubstituted Vinylarenes: A Practical Route
      to Branched gem-Bis(boryl)alkanes.
AB  - We report the first catalytic diborylation of 1,1-disubstituted vinylarenes with
      pinacolborane using a cobalt catalyst generated from bench-stable Co(acac)2 and
      xantphos. A wide range of 1,1-disubstituted vinylarenes underwent this
      transformation to produce the corresponding gem-bis(boryl)alkanes in modest to
      high yields. This cobalt-catalyzed reaction can be readily conducted on a gram
      scale without the use of a dry box and represents a practical and effective
      approach to prepare a wide range of branched gem-bis(boryl)alkanes.

PMID- 29193561
TI  - Effectiveness and tolerability of therapy with exenatide once weekly vs basal
      insulin among injectable-drug-naive elderly or renal impaired patients with type
      2 diabetes in the United States.
AB  - AIM: To evaluate the effectiveness and tolerability of exenatide once weekly
      (EQW) compared with basal insulin (BI) among injectable-drug-naive patients with
      type 2 diabetes mellitus (T2DM) who are elderly or have renal impairment (RI).
      MATERIALS AND METHODS: Initiators of EQW and BI with T2DM were identified for the
      period 2012 to 2015 within a US electronic health record database and matched by
      propensity score. Matched EQW and BI initiators aged >=65 years or who had RI
      were compared. Data on weight, glycated haemoglobin (HbA1c), estimated glomerular
      filtration rate (eGFR), blood pressure and lipids were obtained at baseline and
      quarterly (Q1-Q4) or semi-annually for 1 year after drug initiation.
      Hypoglycaemia and gastrointestinal symptoms were identified using diagnosis codes
      and data abstracted from clinical notes. RESULTS: Among patients aged >=65 years,
      HbA1c changed by -0.50 and -0.31 percentage points from baseline to Q4 for EQW
      and BI initiators, respectively. Weight changed by -1.6 kg among EQW initiators
      compared with 0.2 kg among BI initiators. Compared with BI initiators, EQW
      initiators had a 1.45-fold increased risk of nausea and vomiting. Among patients
      with RI, HbA1c changed by -0.58 and -0.33 percentage points from baseline to Q4
      for EQW and BI initiators, respectively. Weight changed by -1.9 kg for EQW
      initiators while BI initiators had no change in weight. EQW initiators had a 1.28
      fold increased risk of constipation and diarrhoea compared with BI initiators.
      CONCLUSION: Regardless of age or renal function, the benefits of EQW relative to
      BI treatment are improved glycaemic control and increased weight loss, which
      should be weighed against the increased risk of gastrointestinal symptoms.

PMID- 29193562
TI  - Resveratrol-induced thrombocytopenia: Inadvertent side-effect of a commonly used
      antioxidant.

PMID- 29193563
TI  - Sacubitril/valsartan reduces serum uric acid concentration, an independent
      predictor of adverse outcomes in PARADIGM-HF.
AB  - AIMS: Elevated serum uric acid concentration (SUA) has been associated with an
      increased risk of cardiovascular disease, but this may be due to unmeasured
      confounders. We examined the association between SUA and outcomes as well as the
      effect of sacubitril/valsartan on SUA in patients with heart failure with reduced
      ejection fraction (HFrEF) in PARADIGM-HF. METHODS AND RESULTS: The association
      between SUA and the primary composite outcome of cardiovascular death or heart
      failure (HF) hospitalization, its components, and all-cause mortality was
      examined using Cox regression analyses among 8213 patients using quintiles (Q1
      Q5) of SUA adjusted for baseline prognostic variables including estimated
      glomerular filtration rate (eGFR), diuretic dose, and log N-terminal pro-brain
      natriuretic peptide. Change in SUA from baseline over 12 months was also
      evaluated in each treatment group. Patients in Q5 (SUA >=8.6 mg/dL) compared with
      Q1 (<5.4 mg/dL) were younger (62.8 vs. 64.2 years), more often male (88.7% vs.
      63.1%), had lower systolic blood pressure (119 vs. 123 mmHg), lower eGFR (57.4
      vs. 76.6 mL/min/1.73 m2 ), and greater diuretic use. Higher SUA was associated
      with a higher risk of the primary outcome (adjusted hazard ratios) Q5 vs. Q1 =
      1.28 [95% confidence intervals (1.09-1.50), P = 0.003], cardiovascular death
      [1.44 (1.11-1.77), P = 0.001], HF hospitalization [1.37 (1.11-1.70), P = 0.004],
      and all-cause mortality [1.36 (1.13-1.64), P = 0.001]. Compared with enalapril,
      sacubitril/valsartan reduced SUA by 0.24 (0.17-0.32) mg/dL over 12 months (P <
      0.0001). Sacubitril/valsartan improved outcomes, irrespective of SUA
      concentration. CONCLUSION: Serum uric acid concentration was an independent
      predictor of worse outcomes after multivariable adjustment in patients with
      HFrEF. Compared with enalapril, sacubitril/valsartan reduced SUA and improved
      outcomes irrespective of SUA.

PMID- 29193564
TI  - IFN-free therapy is associated with restoration of type I IFN response in HIV-1
      patients with acute HCV infection who achieve SVR.
AB  - Interferon (IFN)-free direct-acting antiviral agents (DAAs) have revolutionized
      chronic hepatitis C virus (HCV) treatment; early studies suggest excellent
      efficacy in acute HCV. However, changes in innate immune responses during DAA
      therapy for acute HCV are unknown. We studied interferon-stimulated gene (ISG)
      expression and related cytokines/chemokines in HIV-infected patients with acute
      HCV receiving sofosbuvir plus ribavirin (SOF+RBV) as part of the A5327 clinical
      trial. ISG expression was determined from PBMCs, and circulating
      cytokines/chemokines were quantified from serum from study participants. The
      overall sustained virologic response (SVR) was 57%; all treatment failures were
      due to virologic relapse. Apart from NOS2a, baseline ISG/chemokine/cytokine
      levels were similar irrespective of treatment outcome. Downregulation of ISGs was
      observed at treatment week four and end of treatment (EOT), implicating HCV in
      establishing elevated ISGs early during HCV infection. Levels of many of these
      ISGs increased at post-treatment week 12 (PTW12) in relapsers only, coinciding
      with recurrent HCV RNA. Eleven ISGs were differentially expressed in responders
      vs relapsers. On-treatment viral suppression was also associated with a reduction
      in IP-10, CXCL11 and MIP-1beta levels. In contrast, circulating IFN-alpha levels
      were significantly higher at EOT and PTW12 in responders vs relapsers.
      Upregulation of peripheral ISG expression is established early in the course of
      HCV infection during acute HCV infection, but did not predict subsequent
      treatment outcome with SOF+RBV. ISGs were downregulated during therapy and
      increased post-therapy in relapsers. IFN-alpha levels were higher in responders
      at EOT/PTW12, suggesting that impaired type I IFN production/secretion may
      contribute to relapse.

PMID- 29193565
TI  - Clinical relevance of spectral tissue Doppler-derived E/e' in the diagnosis of
      heart failure with preserved ejection fraction.

PMID- 29193566
TI  - Systematic review and meta-analysis of algorithms used to identify drug-induced
      liver injury (DILI) in health record databases.
AB  - BACKGROUND & AIMS: Drug induced liver injury (DILI) is largely underreported,
      leading to underestimation of its burden. Electronic detection of DILI in
      healthcare databases shows promise to overcome the issues of spontaneous
      reporting. The performance of detection algorithms may vary because of
      inconsistent DILI definition and detection criteria. We performed a systematic
      review and meta-analysis to identify the DILI detection criteria used in health
      record databases and determine the performance characteristics of the detection
      algorithms. METHODS: We searched PubMed, EMBASE and Scopus for studies that
      utilized laboratory threshold criteria to identify DILI cases. Validation studies
      were included in the meta-analysis. Data were abstracted using standardized forms
      and quality was assessed using modified Quality Assessment of Diagnostic Accuracy
      Studies 2 (QUADAS-2) criteria. We evaluate the performance characteristics of the
      detection algorithm by obtaining the pooled estimate of the positive predictive
      value (PPV) assuming a random effects model. RESULTS: A total of 29 studies met
      the inclusion criteria for the systematic review; 25 of these studies (n = 35
      948) had PPV estimates for performing the meta-analysis. The PPV of DILI
      detection algorithms was low, ranging from 1.0% to 40.2%, with a pooled estimate
      of 14.6% (95% CI 10.7-18.9). Algorithms that performed better had prespecified
      exclusion diagnoses as well as drugs of interest to minimize false positives.
      CONCLUSION: Algorithm performance varied with different case definitions of DILI
      attributed to different laboratory threshold criteria, diagnosis codes, and study
      drugs.

PMID- 29193567
TI  - A case of juvenile pityriasis rubra pilaris type III successfully treated with
      etanercept.

PMID- 29193568
TI  - Language barriers and their impact on provision of care to patients with limited
      English proficiency: Nurses' perspectives.
AB  - AIM AND OBJECTIVE: To explore nurses' perspectives of language barriers and their
      impact on the provision of care to patients with limited English proficiency from
      diverse linguistic background. DESIGN AND METHODS: A qualitative descriptive
      approach was used. Using individual interviews and focus group discussions, data
      were collected from 59 nurses working in tertiary care hospitals in England. A
      thematic analysis was used to analyse the data. FINDINGS: Three themes, "multi
      ethnicities and language barriers," "the impact of language barriers" and
      "communicating via interpreters," were identified. Communication was identified
      as the most important aspect of care provision and an essential component of a
      nurse's professional role regardless of the clinical area or speciality. Language
      barriers were identified as the biggest obstacles in providing adequate,
      appropriate, effective and timely care to patients with limited English
      proficiency. Use of professional interpreters was considered useful; however, the
      limitations associated with use of interpretation service, including arrangement
      difficulties, availability and accessibility of interpreters, convenience,
      confidentiality and privacy-related issues and impact on the patient's comfort
      were mentioned. CONCLUSIONS: Language barriers, in any country or setting, can
      negatively affect nurses' ability to communicate effectively with their patients
      and thereby have a negative impact on the provision of appropriate, timely, safe
      and effective care to meet patient's needs. RELEVANCE TO CLINICAL PRACTICE: An
      understanding of language barriers can help nurses find appropriate strategies to
      overcome such barriers and, consequently, enhance the provision of effective care
      to patients affected by language barriers in any clinical setting in any
      healthcare system. The findings of the study have international relevance as
      language barriers affect healthcare provision in any country or setting.

PMID- 29193569
TI  - 9.4T and 17.6T MRI of Retinoblastoma: Ex Vivo evaluation of microstructural
      anatomy and disease extent compared with histopathology.
AB  - BACKGROUND: Retinoblastoma is the most common intraocular tumor in childhood with
      a good prognosis in terms of mortality, but detailed information about tumor
      morphology and disease extent in retinoblastoma is important for treatment
      decision making. PURPOSE: To demonstrate ultrahigh-field MRI tumor morphology and
      tumor extent in retinoblastoma correlating with in and ex vivo images with
      histopathology. STUDY TYPE: Prospective case series. POPULATION: Six
      retinoblastoma patients (median age 5.5 months, range 2-14) were prospectively
      included in this study. Median time between diagnosis and enucleation was 8 days
      (range 7-19). FIELD STRENGTH/SEQUENCE: In vivo pre-enucleation at 1.5T MRI with a
      circular surface coil. Ex vivo imaging (FLASH T1 -weighted and RARE T2 -weighted)
      was performed at field strengths of 9.4T and 17.6T. ASSESSMENT: After ex vivo
      imaging, the eyes were histopathologically analyzed and morphologically matched
      with MRI findings by three authors (two with respectively 14 and 4 years of
      experience in ocular MRI and one with 16 years of experience in
      ophthalmopathology). RESULTS: Small submillimeter morphological aspects of
      intraocular retinoblastoma were successfully depicted with higher-resolution MRI
      and matched with histopathology images. With ex vivo MRI a small subretinal tumor
      seed (300 MUm) adjacent to the choroid was morphologically matched with
      histopathology. Also, a characteristic geographical pattern of vital tumor tissue
      (400 MUm) surrounding a central vessel interspersed with necrotic areas
      correlated with histopathology images. Tumor invasion into the optic nerve showed
      a higher signal intensity on T1 -weighted higher-resolution MRI. DATA CONCLUSION:
      Higher-resolution MRI allows for small morphological aspects of intraocular
      retinoblastoma and extraocular disease extent not visible on currently used
      clinical in vivo MRI to be depicted. LEVEL OF EVIDENCE: 4 Technical Efficacy:
      Stage 2 J. Magn. Reson. Imaging 2018;47:1487-1497.

PMID- 29193570
TI  - CO Hydrogenation on Cobalt-Based Catalysts: Tin Poisoning Unravels CO in Hollow
      Sites as a Main Surface Intermediate.
AB  - Site poisoning is a powerful method to unravel the nature of active sites or
      reaction intermediates. The nature of the intermediates involved in the
      hydrogenation of CO was unraveled by poisoning alumina-supported cobalt catalysts
      with various concentrations of tin. The rate of formation of the main reaction
      products (methane and propylene) was found to be proportional to the
      concentration of multi-bonded CO, likely located in hollow sites. The specific
      rate of decomposition of these species was sufficient to account for the
      formation of the main products. These hollow-CO are proposed to be main reaction
      intermediates in the hydrogenation of CO under the reaction conditions used here,
      while linear CO are mostly spectators.

PMID- 29193571
TI  - The heart failure readmission quagmire: taking a deep dive to find solutions.

PMID- 29193572
TI  - Incretin-based therapies and risk of pancreatic cancer in patients with type 2
      diabetes: A meta-analysis of randomized controlled trials.
AB  - AIMS: To perform a meta-analysis of randomized controlled trials (RCTs),
      including 6 recently published large-scale cardiovascular outcome trials (CVOTs),
      to evaluate the risk of pancreatic cancer with incretin-based therapies in
      patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: For the period
      January 1, 2007 to May 1, 2017, the PubMed, Embase, Cochrane Central Register and
      ClininalTrials.gov databases were searched for RCTs in people with T2DM that
      compared incretin drugs with placebo or other antidiabetic drugs, with treatment
      and follow-up durations of >=52 weeks. Two reviewers screened the studies,
      extracted the data and assessed the risk of bias independently and in duplicate.
      RESULTS: A total of 33 studies (n = 79 971), including the 6 CVOTs, with 87
      pancreatic cancer events were identified. Overall, the pancreatic cancer risk was
      not increased in patients administered incretin drugs compared with controls
      (Peto odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.02). In the 6
      CVOTs, 79 pancreatic cancer events were identified in 55 248 participants. Pooled
      estimates of the 6 CVOTs showed an identical tendency (Peto OR 0.65, 95% CI 0.42
      1.01). Notably, in the subgroup of participants who received treatment and follow
      up for >=104 weeks, 84 pancreatic cancer events were identified in 59 919
      participants, and a lower risk of pancreatic cancer was associated with incretin
      based therapies (Peto OR 0.62, 95% CI 0.41-0.95). CONCLUSIONS: Treatment with
      incretin drugs was not associated with an increased risk of pancreatic cancer in
      people with T2DM. Instead, it might protect against pancreatic malignancy in
      patients treated for >=104 weeks.

PMID- 29193573
TI  - Great and rapid HBsAg decline in patients with on-treatment hepatitis flare in
      early phase of potent antiviral therapy.
AB  - HBsAg decline during nucleos(t)ide analogue therapy in chronic hepatitis B with
      lower pretherapy ALT is usually small and slow. This study aimed to investigate
      why ~10% of such patients showed "rapid HBsAg decline" >=0.5 log10 IU/mL by month
      6 of therapy. Patients with persistent pretherapy ALT <5X ULN who had qHBsAg at
      baseline, months 6 and 12 of entecavir or tenofovir therapy were studied. "On
      treatment ALT elevation" was defined as >10% increase above baseline to >2X ULN
      during first 6 months of therapy. Of the 256 patients treated, 51 experienced
      transient "on-treatment ALT elevation" [group A], including 30 (11.7%) with ALT
      elevation to 2-5X ULN [group A-1] and 21 (8.2%) flared to >5X ULN [group A-2].
      The magnitude of qHBsAg decline and rate of "rapid HBsAg decline" by month 6 was
      significantly greater and more frequent in group A (-0.446 vs -0.042 log10 IU/mL;
      45.1 vs 8.8%, respectively, P = 0.000) than in the remaining 205 patients without
      on-treatment ALT elevation (group B), being greatest in patients with hepatitis
      flare (group A-2: -0.559 log10 IU/mL and 57.1%, respectively). In patients with
      therapy >=2 years, patients with "on-treatment ALT elevation" also showed
      significantly greater annual HBsAg decline, more frequent to <100 IU/mL and 4
      times higher HBsAg seroclearance rate. "On-treatment ALT elevation," especially
      flare >5X ULN, during entecavir therapy or tenofovir therapy may
      enhance/accelerate HBsAg decline, suggesting the effect of immune restoration
      upon potent viral suppression.

PMID- 29193574
TI  - Norcantharidin induce apoptosis in human nasopharyngeal carcinoma through caspase
      and mitochondrial pathway.
AB  - While Nasopharyngeal carcinoma (NPC) is uncommon in western countries, it is
      endemic in Southeast Asia and Southern China. Previous study of norcantharidin
      (NCTD), isolated from blister beetles, has proved its anticancer effect on
      various tumors. However, the effect of NCTD in NPC has never been studied. The
      purpose of this study is to inspect the suppression activity of NCTD on NPC,
      along with the underlying mechanism. NPC cell line NPC-BM was treated with NCTD.
      NCTD remarkably inhibited proliferation and induce apoptosis in NPC-BM cell.
      Activation of caspase-3, -8, -9 was observed through western blotting. The
      expression of antiapoptotic protein Bcl-XL was significantly reduced, but
      expression of proapoptotic protein Bak was increased after treatment of NCTD. The
      cytotoxic effect of NCTD on NPC-BM cell is mainly due to apoptosis, mediated by
      caspase and mitochondrial pathway. These results suggested that NCTD could be a
      potential anticancer agent for NPC.

PMID- 29193575
TI  - Ethanol-mediated suppression of IL-37 licenses alcoholic liver disease.
AB  - BACKGROUND & AIMS: Chronic alcohol consumption and alcoholic liver disease (ALD)
      afflicts individuals with substantial morbidity and mortality with limited
      treatment options available. Hepatic inflammation, triggered by activated Kupffer
      cells, is a driving force in alcoholic liver disease. Interleukin 37 (IL-37)
      exerts anti-inflammatory effects in hepatic diseases, however, the impact of
      Interleukin 37 on alcoholic liver disease is unknown. In this study, we addressed
      the role of Interleukin 37 in alcoholic liver disease. METHODS: We utilized
      Interleukin 37 expressing transgenic mice and human recombinant Interleukin 37 in
      models of alcoholic liver disease. Interleukin 37 expression was measured in
      liver samples of 20 alcoholic steatohepatitis and 36 non-alcoholic fatty liver
      disease patients. RESULTS: Interleukin 37 transgenic mice are not protected
      against hepatic injury and inflammation in alcoholic liver disease. Ethanol
      suppressed Interleukin 37 expression in transgenic mice. Alcoholic
      steatohepatitis (ASH) patients similarly exhibited reduced Interleukin 37
      expression when compared to non-alcoholic fatty liver disease (NAFLD) patients.
      Human recombinant Interleukin 37 ameliorated hepatic inflammation in a binge
      drinking model of alcoholic liver disease. CONCLUSION: We provide evidence for an
      exogenous noxae that suppresses Interleukin 37 expression which limits its anti
      inflammatory effects in alcoholic liver disease.

PMID- 29193576
TI  - Adaptive servo-ventilation for central sleep apnoea in systolic heart failure:
      results of the major substudy of SERVE-HF.
AB  - AIMS: The SERVE-HF trial investigated the impact of treating central sleep apnoea
      (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart
      failure. A preplanned substudy was conducted to provide insight into mechanistic
      changes underlying the observed effects of ASV, including assessment of changes
      in left ventricular function, ventricular remodelling, and cardiac, renal and
      inflammatory biomarkers. METHODS AND RESULTS: In a subset of the 1325 randomised
      patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and
      biomarker analysis were performed at baseline, and 3 and 12 months. In secondary
      analyses, data for patients with baseline and 12-month values were evaluated; 312
      patients participated in the substudy. The primary endpoint, change in
      echocardiographically determined left ventricular ejection fraction from baseline
      to 12 months, did not differ significantly between the ASV and the control
      groups. There were also no significant between-group differences for changes in
      left ventricular dimensions, wall thickness, diastolic function or right
      ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in
      small patient numbers). Plasma N-terminal pro B-type natriuretic peptide
      concentration decreased in both groups, and values were similar at 12 months.
      There were no significant between-group differences in changes in cardiac, renal
      and systemic inflammation biomarkers. CONCLUSION: In patients with systolic heart
      failure and CSA, addition of ASV to guideline-based medical management had no
      statistically significant effect on cardiac structure and function, or on cardiac
      biomarkers, renal function and systemic inflammation over 12 months. The
      increased cardiovascular mortality reported in SERVE-HF may not be related to
      adverse remodelling or worsening heart failure.

PMID- 29193580
TI  - Stomas: time for a closer look.

PMID- 29193577
TI  - Commentary on 'Robotic vs laparoscopic rectal surgery in high-risk patients'.

PMID- 29193585
TI  - Unravelling the Carbohydrate-Binding Preferences of the Carbohydrate-Binding
      Modules of AMP-Activated Protein Kinase.
AB  - The beta subunit of adenosine monophosphate (AMP)-activated protein kinase
      (AMPK), which exists as two isoforms (beta1 and beta2) in humans, has a
      carbohydrate-binding module (CBM) that interacts with glycogen. Although the
      beta1- and beta2-CBMs are structurally similar, with strictly conserved ligand
      contact residues, they show different carbohydrate affinities. beta2-CBM shows
      the strongest affinity for both branched and unbranched oligosaccharides and it
      has recently been shown that a Thr insertion into beta2-CBM (Thr101) forms a
      pocket to accommodate branches. This insertion does not explain why beta2-CBM
      binds all carbohydrates with stronger affinity. Herein, it is shown that residue
      134 (Val for beta2 and Thr for beta1), which does not come into contact with a
      carbohydrate, appears to account for the affinity difference. Characterisation by
      NMR spectroscopy, however, suggests that mutant beta2-Thr101Delta/Val134Thr
      differs from that of beta1-CBM, and mutant beta1-Thr101ins/Thr134Val differs from
      that of beta2-CBM. Furthermore, these mutants are less stable to chemical
      denaturation, relative to that of wild-type beta-CBMs, which confounds the
      affinity analyses. To support the importance of Thr101 and Val134, the ancestral
      CBM has been constructed. This CBM retains Thr101 and Val134, which suggests that
      the extant beta1-CBM has a modest loss of function in carbohydrate binding.
      Because the ancestor bound carbohydrate with equal affinity to that of beta2-CBM,
      it is concluded that residue 134 plays an indirect role in carbohydrate binding.

PMID- 29193584
TI  - Contraceptive Choice and Use of Dual Protection Among Women Living with HIV in
      Canada: Priorities for Integrated Care.
AB  - CONTEXT: Preventing unintended pregnancy and HIV transmission is important for
      women with HIV, but little is known about their contraceptive use, particularly
      under current antiretroviral therapy (ART) recommendations for treatment and
      prevention. METHODS: The prevalence of contraceptive use and of dual protection
      was examined among 453 sexually active women with HIV aged 16-49 and enrolled in
      the Canadian HIV Women's Sexual and Reproductive Health Cohort Study in 2013
      2015; multivariable logistic regression was used to identify correlates of use.
      Two definitions of dual protection were assessed: the World Health Organization
      (WHO) definition (consistent condom use alongside another effective method) and
      an expanded definition (consistent condom use or a suppressed HIV viral load
      alongside an effective method). RESULTS: Overall, 73% of women used effective
      contraceptives, primarily male condoms (45%) or tubal ligation (19%). Eighteen
      percent practiced WHO-defined dual protection, and 40% practiced dual protection
      according to the expanded definition. Characteristics positively associated with
      contraceptive use were younger age, having been pregnant, being heterosexual,
      being unaware of ART's HIV prevention benefits and having had partners of unknown
      HIV status (odds ratios, 1.1-6.7). Younger age and perceived inability to become
      pregnant were positively associated with both definitions of dual protection
      (1.04-3.3); additionally, WHO-defined dual protection was associated with
      perceiving HIV care to be women-centered and having had partners of unknown HIV
      status (2.0-4.1), and dual protection under the expanded definition was related
      to having been pregnant (2.7). CONCLUSIONS: Future research should explore how
      sustained ART and broader contraceptive options can support women's sexual and
      reproductive health care needs.

PMID- 29193586
TI  - Brass and Bronze as Effective CO2 Reduction Electrocatalysts.
AB  - Electrochemically reducing CO2 into fuels using renewable electricity is a
      contemporary global challenge that requires significant advances in catalyst
      design. Photodeposition techniques were used to screen ternary alloys of Cu-Zn
      Sn, which includes brass and bronze, for the electrocatalytic reduction of CO2 to
      CO and formate. This analysis identified Cu0.2 Zn0.4 Sn0.4 and Cu0.2 Sn0.8 to be
      capable of reaching Faradaic efficiencies of >80 % for CO and formate formation,
      respectively, and capable of achieving partial current densities of 3 mA cm-2 at
      an overpotential of merely 200 mV.

PMID- 29193587
TI  - Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male
      rats.
AB  - Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its
      association with asbestos exposure. Malignant mesothelioma is difficult to
      diagnose at an early stage, yet there are no particularly effective treatments
      available at the advanced stage, thus necessitating efficient strategies to
      prevent MM in individuals already exposed to asbestos. We previously showed that
      persistent oxidative damage caused by foreign body reaction and affinity of
      asbestos both to hemoglobin and histones is one of the major pathogeneses.
      Accordingly, as an effective strategy to prevent asbestos-induced MM, we
      undertook the use of an iron chelator, deferasirox, which decreased the
      epithelial-mesenchymal transition in a crocidolite-induced rat MM model. However,
      this agent may show adverse effects. Here, we studied the effects of iron removal
      by phlebotomy as a realistic measure on the same rat model. We injected a total
      of 5 mg crocidolite i.p. to F1 hybrid rats between the Fischer-344 and Brown
      Norway strains at the age of 6 weeks. We repeated weekly or biweekly phlebotomy
      of 6-8 mL/kg/time from 10 to 60 weeks of age. The animals were observed until 120
      weeks. In male rats, phlebotomy significantly decreased the weight and nuclear
      grade of MM, and modestly reduced the associated ascites and the fraction of more
      malignant sarcomatoid subtype. Weekly phlebotomy prolonged long-term survival.
      Our results indicate that appropriate phlebotomy may be a practical preventive
      measure to attenuate the initiation and promotion capacity of asbestos towards MM
      by reducing iron in individuals exposed to asbestos.

PMID- 29193588
TI  - Long-term evidence that a pediatric oncology mentorship program for young
      investigators is feasible and beneficial in the cooperative group setting: A
      report from the Children's Oncology Group.
AB  - BACKGROUND: Mentorship of junior faculty is an integral component of career
      development. The Children's Oncology Group (COG) Young Investigator (YI)
      Committee designed a mentorship program in 2004 whose purpose was to pair YIs
      (faculty <=10 years of first academic appointment) with a senior mentor to assist
      with career development and involvement in COG research activities. This study
      reports on the committee's ability to achieve these goals. PROCEDURE: An online
      survey was sent to YIs who were registered with the program from 2004 to2015,
      assessing three major domains: (1) overall experience with the mentor pairing,
      (2) satisfaction with the program, and (3) academic accomplishments of the
      mentees. RESULTS: The response rate was 64% (110/171). Overall, YIs rated the
      success of their mentorship pairing as 7.2 out of 10 (median) (25th, 75th
      quartile 3.6, 9.6). The direct effects of the mentorship program included 70% YIs
      reporting a positive effect on their career, 40% reporting any grant or
      manuscript resulting from the pairing, 47% forming a new research collaboration,
      and 43% receiving appointment to a COG committee. Respondents reported success in
      COG with 38% authoring a manuscript on behalf of COG and 65% reporting a
      leadership position including seven current or past COG discipline chairs and 20
      study chairs. Finally, 74% of respondents said they would consider serving as
      mentors in the program in the future. CONCLUSION: The COG YI mentorship program
      has been well received by the majority of the participants and has helped to
      identify and train many current leaders in COG.

PMID- 29193589
TI  - Corrigendum.

PMID- 29193590
TI  - Corrigendum.

PMID- 29193591
TI  - Patient perceptions of deterioration and patient and family activated escalation
      systems-A qualitative study.
AB  - AIMS AND OBJECTIVES: To investigate the experiences of patients who received a
      medical emergency team review following a period of clinical deterioration and
      their views about the potential use of a patient and family activated escalation
      system. BACKGROUND: Delay or failure by health professionals to respond to
      clinical deterioration remains a patient safety concern. Patients may sometimes
      identify subtle cues of early deterioration prior to changes in vital signs. In
      response to health professional and system failures, patient and family activated
      escalation systems have been mandated and implemented in Australia. However,
      little research has evaluated their effectiveness nor taken patients'
      perspectives into account. DESIGN: Qualitative exploratory descriptive design was
      used. METHODS: Purposive sampling was used. Semistructured interviews were
      undertaken in 2014 with 33 patients who required medical emergency team
      intervention. Data were collected from one private and one public hospital in
      Melbourne, Victoria, Australia. The framework method was used to analyse the
      data. RESULTS: All patients stated that it was the clinician who detected and
      responded to deterioration. Private patient participants were unaware of the
      medical emergency team system, and felt escalating care was not their
      responsibility. These patients reported being too sick to communicate prior to
      and during medical emergency team review and did not favour a patient and family
      activated escalation system. Public patients were well informed about the medical
      emergency team system yet expressed concerns around overriding clinicians if
      activating a patient and family activated escalation system. CONCLUSION: Patient
      participation during a period of deterioration is restricted by their clinical
      condition and limited medical knowledge. Patients felt comfortable to communicate
      concerns to clinicians but felt they would not activate the patient and family
      activated escalation system. This behoves clinicians to actively listen and
      respond to patient concerns. RELEVANCE TO CLINICAL PRACTICE: Clinicians must
      promote a collaborative relationship and encourage patients to communicate their
      concerns. Given the perceived barriers to patient and family activated escalation
      systems use, resources being employed for their implementation could be
      redistributed to other areas of patient safety.

PMID- 29193592
TI  - Gilbert Stork (1921-2017).
AB  - Gilbert Stork, professor emeritus at Columbia University, died on October 21,
      2017 at the age of 95. Stork will be remembered as one of the greatest
      practitioners of the art of organic synthesis. He achieved landmark successes in
      simple and elegant total syntheses in virtually every natural product class:
      terpenes, alkaloids, prostaglandins, macrolides, and tetracyclines.

PMID- 29193593
TI  - Concomitant nonalcoholic fatty liver disease does not alter the activity,
      severity or course of primary biliary cholangitis.
AB  - BACKGROUND & AIMS: The impact of nonalcoholic fatty liver disease (NAFLD) on the
      natural history of primary biliary cholangitis (PBC) has yet to be described. The
      aim of this study was to document the activity, severity and progression of PBC
      in patients with concomitant NAFLD and compare the findings to those with PBC
      alone. METHODS: Disease activity was assessed by serum liver enzyme levels;
      severity, by Fib-4 scores and percent of patients with APRI >1.5; and
      progression, by changes in Fib-4 and prevalence of APRI >1.5 during follow-up.
      RESULTS: The study populations consisted of 168 PBC alone and 68 PBC/NAFLD
      patients. The mean ages and gender distributions of the two cohorts were similar.
      At presentation, PBC alone patients had greater disease activity (higher serum
      ALP and GGT values, P = .003 and 0.01, respectively) and advanced disease (higher
      Fib-4 (P = .04) scores) than PBC/NAFLD patients. Although the prevalence of APRI
      >1.5 was also higher in PBC alone (11.1%) vs PBC/NAFLD (4.7%) patients, the
      difference was not significant (P = .16). During mean follow-up of 6.7 +/- 5.5
      (PBC alone) and 6.4 +/- 4.4 (PBC/NAFLD) years (ranges: 0.5-21 years) annual
      increases in Fib-4 and prevalence of >= APRI 1.5 were greater in PBC alone
      patients but the differences did not reach statistical significance. CONCLUSIONS:
      The results of this retrospective, single centre study suggest that the activity,
      severity and progression of PBC are not adversely affected by concomitant NAFLD.

PMID- 29193595
TI  - Fellows of the Electrochemical Society: C. Amatore, K. Amine, P. Atanassov, C. P.
      Grey, Y. Shao-Horn, and N. Wu / Priestley Medal: G. Richmond / Forderungspreis
      der Stadt Wien: N. Maulide.

PMID- 29193594
TI  - Complete cure of Fusarium solani sp. complex onychomycosis with Qs NdYAG
      treatment.
AB  - The incidence of non dermatophytic mould (NDM) onychomycosis (OM) has been
      steadily increasing Fusarium spp is the most common cause of NDM OM in most
      geographical locations. Fusarium spp and other NDMs are largely resistant to
      commonly used anti-fungals. The successful use of laser and light based devices
      has been demonstrated in dermatophytic OM, but there is no previous report of
      their successful use in any NDM OM. We describe a patient with OM caused by
      Fusarium solani spp, who was clinically (with a normal appearing nail) and
      mycologically (with negative microscopy and culture on repeated samples) cured of
      her infection following treatment with 2 sessions of Qs NdYAG (532nm and 1064nm)
      given 1 month apart.

PMID- 29193596
TI  - Superiorly based facial artery musculomucosal flap: A versatile pedicled flap.
AB  - BACKGROUND: The superiorly based facial artery musculomucosal (FAMM) flap is
      pedicled on the angular artery. This flap offers a well-vascularized mucosal
      surface allowing closure of medium size defects, most frequently within the oral
      cavity and intranasal region. METHODS: We describe a superiorly based harvest of
      the FAMM flap, which may be used for closure of multiple head and neck surgical
      defects. An operative technique video is provided, which can be viewed online.
      RESULTS: Our results demonstrate a fast and relatively straightforward harvest
      technique of the FAMM flap. This intraoral flap is a useful reconstructive tool,
      which also has the advantage to leave no visible external scars. CONCLUSION: The
      superiorly pedicled FAMM flap is a versatile and effective technique that may be
      integrated in the algorithm for reconstruction of head and neck defects.

PMID- 29193597
TI  - Mycotic pseudoaneurysm of a pulmonary artery branch caused by Cladosporium.
AB  - We report the case of a 53-year-old male with a history of acute myelogenous
      leukemia, who suffered the rupturing of a right-sided pulmonary artery
      pseudoaneurysm combined with pneumonia. He underwent a right-sided lower
      lobectomy. The resected lung tissue demonstrated a mycotic pseudoaneurysm of a
      pulmonary artery branch together with a filamentous fungal infection.
      Pseudoaneurysms are caused by the breaching of all layers of a blood vessel wall.
      The extravasated blood is trapped by the surrounding extravascular tissue or
      clots. Cladosporium was detected during a polymerase chain reaction-based
      analysis followed by DNA sequencing of formalin-fixed paraffin-embedded lung
      tissue samples. Although previous cases of pulmonary artery pseudoaneurysms
      caused by fungal infections, e.g., Candida or Aspergillus sp., have been
      reported, to the best of our knowledge this is the first case to involve
      cladosporiosis.

PMID- 29193598
TI  - Pseudomonas fluorescens Strain R124 Encodes Three Different MIO Enzymes.
AB  - A number of class I lyase-like enzymes, including aromatic ammonia-lyases and
      aromatic 2,3-aminomutases, contain the electrophilic 3,5-dihydro-5-methylidene-4H
      imidazol-4-one (MIO) catalytic moiety. This study reveals that Pseudomonas
      fluorescens R124 strain isolated from a nutrient-limited cave encodes a histidine
      ammonia-lyase, a tyrosine/phenylalanine/histidine ammonia-lyase (XAL), and a
      phenylalanine 2,3-aminomutase (PAM), and demonstrates that an organism under
      nitrogen-limited conditions can develop novel nitrogen fixation and
      transformation pathways to enrich the possibility of nitrogen metabolism by
      gaining a PAM through horizontal gene transfer. The novel MIO enzymes are
      potential biocatalysts in the synthesis of enantiopure unnatural amino acids. The
      broad substrate acceptance and high thermal stability of PfXAL indicate that this
      enzyme is highly suitable for biocatalysis.

PMID- 29193600
TI  - Mammographic density and other risk factors for breast cancer among women in
      China.

PMID- 29193599
TI  - Characterization of mice carrying a conditional TEAD1 allele.
AB  - The Hippo- yes-associated protein (YAP) pathway is essential for controlling
      organ size and tumorigenesis. Previous studies have demonstrated that the primary
      outcome of YAP signaling in the nucleus is achieved by interaction with the
      transcription factor TEA domain transcription factor (TEAD1). The YAP/TEAD1
      complex binds to DNA element and regulates the expression of genes involved in
      cell growth. However, constitutive knockout of TEAD1 leads to early embryonic
      lethality in mice. Thus, generation of a floxed TEAD1 mouse becomes crucial for
      further understanding mid- to late-gestation and post-natal role of TEAD1.
      Herein, we created and characterized a mouse model that allows for conditional
      disruption of TEAD1. Embryonic fibroblasts derived from the floxed TEAD1 mice
      enabled the Cre-mediated deletion of TEAD1 in vitro using virally delivered Cre
      recombinase. Furthermore, crossing the floxed TEAD1 mouse with a ubiquitously
      expressing Cre mouse resulted in efficient ablation of the floxed allele in vivo,
      and the animals recapitulated early embryonic lethality defects. In conclusion,
      our data demonstrate an important role of TEAD1 in early development in mice, and
      the floxed TEAD1 mouse model will be a valuable genetic tool to determine the
      temporal and tissue-specific functions of TEAD1.

PMID- 29193601
TI  - A Hierarchical MFI Zeolite with a Two-Dimensional Square Mesostructure.
AB  - A conceptual design and synthesis of ordered mesoporous zeolites is a challenging
      research subject in material science. Several seminal articles report that one
      dimensional (1D) mesostructured lamellar zeolites are possibly directed by sheet
      assembly of surfactants, which collapse after removal of intercalated
      surfactants. However, except for one example of two-dimensional (2D) hexagonal
      mesoporous zeolite, no other zeolites with ordered 2D or three-dimensional (3D)
      mesostructures have been reported. An ordered 2D mesoporous zeolite can be
      templated by a cylindrical assembly unit with specific interactions in the
      hydrophobic part. A template molecule with azobenzene in the hydrophobic tail and
      diquaternary ammonium in the hydrophilic head group directs hierarchical MFI
      zeolite with a 2D square mesostructure. The material has an elongated octahedral
      morphology, and quaternary, ordered, straight, square channels framed by MFI thin
      sheets expanded along the a-c planes and joined with 90 degrees  rotations. The
      structural matching between the cylindrical assembly unit and zeolite framework
      is crucial for mesostructure construction.

PMID- 29193602
TI  - The role of zinc in the treatment of acne: A review of the literature.
AB  - Acne vulgaris is a chronic disease of the pilosebaceous units presenting as
      inflammatory or noninflammatory lesions in individuals of all ages. The current
      standard of treatment includes topical formulations in the forms of washes, gels,
      lotions, and creams such as antibiotics, antibacterial agents, retinoids, and
      comedolytics. Additionally, systemic treatments are available for more severe or
      resistant forms of acne. Nevertheless, these treatments have shown to induce a
      wide array of adverse effects, including dryness, peeling, erythema, and even
      fetal defects and embolic events. Zinc is a promising alternative to other acne
      treatments owing to its low cost, efficacy, and lack of systemic side effects. In
      this literature review, we evaluate the effectiveness and side-effect profiles of
      various formulations of zinc used to treat acne.

PMID- 29193603
TI  - Quality of life in adolescents with hepatitis C treated with sofosbuvir and
      ribavirin.
AB  - Chronic HCV infection has been associated with impairment of HRQL in both adults
      and paediatric patients. Our aim was to assess the HRQL of HCV-positive children
      treated with SOF + RBV. The data for this post hoc analysis were collected in a
      phase 2 open-label multinational study that evaluated safety and efficacy of SOF
      (400 mg/day) plus RBV (weight-based up to 1400 mg/day) for 12 or 24 weeks in
      adolescents with chronic HCV (GS-US-334-1112). Patients and their
      parents/guardians completed the PedsQL-4.0-SF-15 questionnaire at baseline, at
      the end of treatment and in post-treatment follow-up. We included 50 adolescents
      with HCV genotype 2 and 3 without cirrhosis (14.8 +/- 1.9 years; male: 58%;
      treatment-naive: 82%; vertically transmitted HCV: 70%). After treatment, 100% of
      patients with HCV genotype 2 and 95% with genotype 3 achieved SVR-12. During
      treatment with SOF + RBV, there were no significant decrements in any of
      patients' self-reported or parent-proxy-reported PRO scores regardless of
      treatment duration (all P > .05). After treatment cessation, we recorded a
      statistically significant improvement in patients' self-reported Social
      Functioning score by post-treatment week 12: on average, +4.8 points on a 0-100
      scale (P = .02). By post-treatment week 24, parent-proxy-reported School
      Functioning score increased by, on average, +13.0 points (P = .0065). In
      multivariate analysis, history of abdominal pain and psychiatric disorders were
      predictive of impaired HRQL in adolescents with HCV (P < .05). Adolescents with
      HCV do not seem to experience any HRQL decrement during treatment with SOF + RBV
      and experience some improvement of their HRQL scores after achieving SVR.

PMID- 29193604
TI  - First insights into insecticidal activity against Aedes aegypti and partial
      biochemical characterization of a novel low molecular mass chymotrypsin-trypsin
      inhibitor purified from Lonchocarpus sericeus seeds.
AB  - BACKGROUND: Arboviroses such as dengue, Zika and chikungunya represent a serious
      public health issue as a consequence of the absence of approved vaccines or
      specific antiviral drugs against the arboviruses that cause them. One way to
      prevent these diseases is by combating the vector mosquito, Aedes aegypti
      (Diptera), which has serine proteases in the midgut. Protease inhibitors are
      molecules that can block enzyme activity, impairing digestion and nutrition,
      which can lead to death. Thus, we purified and characterized a novel chymotrypsin
      trypsin inhibitor (LsCTI) from Lonchocarpus sericeus seeds and investigated its
      effect upon Ae. aegypti egg hatching, larval development and digestive proteases.
      RESULTS: LsCTI showed a single protein band in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), and the molecular mass determined
      by matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) was 8870.45 Da. Kinetics analyses revealed a noncompetitive type
      of inhibition and low inhibition constant (Ki ) for chymotrypsin (8.24 x 10-8 m).
      The thermal resistance was remarkable, even at 100  degrees C for 180 min. The
      inhibitor concentration required for 50-percent enzyme inhibition (IC50 ) of
      LsCTI was 4.7 x 10-7 m for Ae. aegypti midgut larval enzymes. LsCTI did not
      affect egg hatchability at 0.3 mg mL-1 , but caused a high larval mortality rate
      (77%) and delayed development (37%). CONCLUSIONS: LsCTI is a novel protease
      inhibitor with remarkable biochemical characteristics and is a potential tool to
      control Ae. aegypti development. (c) 2017 Society of Chemical Industry.

PMID- 29193605
TI  - Dihydroxyacetone induces G2/M arrest and apoptotic cell death in A375P melanoma
      cells.
AB  - The active ingredient in sunless tanning products (STPs) is a simple sugar,
      dihydroxyacetone (DHA). Several studies have demonstrated that DHA is absorbed
      within the viable layers of skin and not fully contained within the stratum
      corneum. Additionally, spray tanning and other aerosolized application methods
      have increased the risk of internal exposure through mucous membranes and
      inhalation. Beyond its presence in STPs, DHA also occurs as an endogenous by
      product of fructose metabolism, and an excess of DHA in cells can induce advanced
      glycation end (AGE) products and oxidative stress. Therefore, exogenous and
      endogenous exposures to DHA may be harmful to cells, and it has already been
      demonstrated that exogenous exposure to DHA is cytotoxic in immortalized
      keratinocytes. Still, little is known about the exogenous DHA exposure effects on
      other skin components. In this study, we explore the effects of exogenous DHA
      exposure in a human melanoma cell line, A375P. Melanoma cells were sensitive to
      DHA and displayed a transient burst of reactive oxygen species within an hour of
      exposure. Cell cycle arrest at G2/M was observed within 24 h of exposure, and
      apoptosis, monitored by the cleavage of PARP-1 and Caspase-3, was detected within
      72 h of exposure to DHA. Together, these demonstrate that exogenous exposure to
      DHA has cytotoxic effects in our selected cell model and indicates the need to
      further investigate the exogenous exposure effects of DHA in other relevant
      exposure models.

PMID- 29193606
TI  - Real-time probe tracking using EM-optical sensor for MRI-guided cryoablation.
AB  - BACKGROUND: A method of real-time, accurate probe tracking at the entrance of the
      MRI bore is developed, which, fused with pre-procedural MR images, will enable
      clinicians to perform cryoablation efficiently in a large workspace with image
      guidance. METHODS: Electromagnetic (EM) tracking coupled with optical tracking is
      used to track the probe. EM tracking is achieved with an MRI-safe EM sensor
      working under the scanner's magnetic field to compensate the line-of-sight issue
      of optical tracking. Unscented Kalman filter-based probe tracking is developed to
      smooth the EM sensor measurements when occlusion occurs and to improve the
      tracking accuracy by fusing the measurements of two sensors. RESULTS: Experiments
      with a spine phantom show that the mean targeting errors using the EM sensor
      alone and using the proposed method are 2.21 mm and 1.80 mm, respectively.
      CONCLUSION: The proposed method achieves more accurate probe tracking than using
      an EM sensor alone at the MRI scanner entrance.

PMID- 29193608
TI  - Synthesis of Low-Dimensional Polyion Complex Nanomaterials via Polymerization
      Induced Electrostatic Self-Assembly.
AB  - Nanostructured polyion complexes (PICs) are appealing in biomaterials
      applications. Yet, conventional assembly suffers from the weakness in scale-up
      and reproducibility. Only a few low-dimensional PICs are available to date.
      Herein we report an efficient and scalable strategy to prepare libraries of low
      dimensional PICs. It involves a visible-light-mediated RAFT polymerization of
      ionic monomer in the presence of a polyion of the opposite charge at 5-50 % w/w
      total solids concentration in water at 25  degrees C, namely, polymerization
      induced electrostatic self-assembly (PIESA). A Vesicle, multi-compartmental
      vesicle, and large-area unilamellar nanofilm can be achieved in water. A long
      nanowire and porous nanofilm can be prepared in methanol/water. An unusual
      unimolecular polyion complex (uPIC)-sphere-branch/network-film transition is
      reported. This green chemistry offers a general platform to prepare various low
      dimensional PICs with high reproducibility on a commercially viable scale under
      eco-friendly conditions.

PMID- 29193607
TI  - Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma
      metastasis.
AB  - Metastasis is the leading cause of death in patients with advanced melanoma, yet
      the somatic alterations that aid tumour cell dissemination and colonisation are
      poorly understood. Here, we deploy comparative genomics to identify and validate
      clinically relevant drivers of melanoma metastasis. To do this, we identified a
      set of 976 genes whose expression level was associated with a poor outcome in
      patients from two large melanoma cohorts. Next, we characterised the genomes and
      transcriptomes of mouse melanoma cell lines defined as weakly metastatic, and
      their highly metastatic derivatives. By comparing expression data between
      species, we identified lunatic fringe (LFNG), among 28 genes whose expression
      level is predictive of poor prognosis and whose altered expression is associated
      with a prometastatic phenotype in mouse melanoma cells. CRISPR/Cas9-mediated
      knockout of Lfng dramatically enhanced the capability of weakly metastatic
      melanoma cells to metastasise in vivo, a phenotype that could be rescued with the
      Lfng cDNA. Notably, genomic alterations disrupting LFNG are found exclusively in
      human metastatic melanomas sequenced as part of The Cancer Genome Atlas. Using
      comparative genomics, we show that LFNG expression plays a functional role in
      regulating melanoma metastasis.

PMID- 29193609
TI  - Endogenous hormone 2-methoxyestradiol suppresses venous hypertension-induced
      angiogenesis through up- and down-regulating p53 and id-1.
AB  - Brain arteriovenous malformations (AVMs) which associate with angiogenesis due to
      local hypertension, chronic cerebral ischaemia and tissue hypoxia usually lead to
      haemorrhage, however, the therapeutic medicine for the disease is still lacking.
      2-methoxyestradiol (2-ME) has been shown effective in the anti-angiogenic
      treatment. This study was conducted to examine whether and how 2-ME could improve
      the vascular malformations. Intracranial venous hypertension (VH) model produced
      in adult male Sprague-Dawley rats and culture of human umbilical vein endothelial
      cells (HUVECs) at the anoxia condition were used to induce in vivo and in vitro
      angiogenesis, respectively. Lentiviral vectors of ID-1 and p53 genes and of their
      siRNA were intracranially injected into rats and transfected into HUVECs to
      overexpress and down-regulate these molecules. 2-ME treatment not only reduced
      the in vivo progression of brain tissue angiogenesis in the intracranial VH rats
      and the in vitro increases in microvasculature formation, cellular migration and
      HIF-1alpha expression induced by anoxia in HUVECs but also reversed the up
      regulation of ID-1 and down-regulation of p53 in both the in vivo and in vitro
      angiogenesis models. All of the anti-angiogenesis effects of 2-ME observed in VH
      rats and anoxic HUVECs were abrogated by ID-1 overexpression and p53 knockdown.
      Our data collectively suggest that 2-ME treatment inhibits hypoxia/anoxia-induced
      angiogenesis dependently on ID-1 down-regulation and p53 up-regulation, providing
      a potential alternative medical treatment for un-ruptured AVM patients.

PMID- 29193610
TI  - Influence of weight concerns on breastfeeding: Evidence from the Norwegian mother
      and child cohort study.
AB  - OBJECTIVES: High body mass index (BMI) often predicts truncated breastfeeding,
      although why is unclear. We test a proposed mediating role of body concerns on
      breastfeeding initiation and child's age at weaning using longitudinal data for
      55,522 mothers from the Norwegian Mother and Child Cohort Study (MoBa). METHODS:
      A linear regression-based mediation analysis with bootstrapping estimates the
      indirect effects of BMI on breastfeeding decisions (ever-initiation of
      breastfeeding, child's age at weaning, and duration of any breastfeeding beyond
      six months) through the variables of concern around prepregnancy weight and
      weight gains due to pregnancy. RESULTS: Contrary to prediction, Norwegian mothers
      with greater prepregnancy weight concerns had a higher likelihood of initiating
      breastfeeding. Concerns about weight gain during pregnancy, however, predicted
      earlier weaning. This relationship was the same for higher and lower BMI mothers.
      CONCLUSION: In this very large sample, body image affects some breastfeeding
      decisions. However, this effect is independent of mother's body size.

PMID- 29193611
TI  - Effect of the cross-talk between autophagy and endoplasmic reticulum stress on Mn
      induced alpha-synuclein oligomerization.
AB  - Overexposure to manganese (Mn) has been known to induce alpha-synuclein (alpha
      Syn) oligomerization, which is degraded mainly depending on endoplasmic reticulum
      stress (ER stress) and autophagy pathways. However, little data reported the
      cross-talk between ER stress and autophagy on Mn-induced alpha-Syn
      oligomerization. To explore the relationship between ER stress and autophagy, we
      used 4-phenylbutyric acid (4-PBA, the ER stress inhibitor), rapamycin (Rap,
      autophagy activator) and 3-methyladenine (3-MA, autophagy inhibitor) in mice
      model of manganism. After 4 weeks of treatment with Mn, both ER stress and
      autophagy were activated. Exposed to Mn also resulted in alpha-Syn
      oligomerization and neuronal cell damage in the brain tissue of mice, which could
      be relieved by 4-PBA pretreatment. Moreover, when the ER stress was inhibited,
      the activation of autophagy was also inhibited. Rap pretreatment significantly
      activated autophagy and decreased alpha-Syn oligomers. However, 3-MA pretreatment
      inhibited autophagy resulting in increase of alpha-Syn oligomers, and
      compensatorily activated PERK signaling pathway. Our results also demonstrated
      that the inhibition of autophagy by 3-MA aggravated neuronal cell damage. The
      findings clearly demonstrated that the cross-talking between autophagy and ER
      stress might play an important role in the alpha-Syn oligomerization and
      neurotoxicity by Mn.

PMID- 29193612
TI  - A direct role for hepatitis B virus X protein in inducing mitochondrial membrane
      permeabilization.
AB  - Hepatitis B virus X protein (HBx) acts as a multifunctional protein that
      regulates intracellular signalling pathways during HBV infection. It has mainly
      been studied in terms of its interaction with cellular proteins. Here, we show
      that HBx induces membrane permeabilization independently of the mitochondrial
      permeability transition pore complex. We generated mitochondrial outer membrane
      mimic liposomes to observe the direct effects of HBx on membranes. We found that
      HBx induced membrane permeabilization, and the region comprising the
      transmembrane domain and the mitochondrial-targeting sequence was sufficient for
      this process. Membrane permeabilization was inhibited by nonselective channel
      blockers or by N-(n-nonyl)deoxynojirimycin (NN-DNJ), a viroporin inhibitor.
      Moreover, NN-DNJ inhibited HBx-induced mitochondrial depolarization in Huh-7
      cells. Based on the results of this study, we can postulate that the HBx protein
      itself is sufficient to induce mitochondrial membrane permeabilization. Our
      finding provides important information for a strategy of HBx targeting during HBV
      treatment.

PMID- 29193613
TI  - Integrating Trauma-Informed Care Into Maternity Care Practice: Conceptual and
      Practical Issues.
AB  - Adverse childhood experiences have a strong negative impact on health and are a
      significant public health concern. Adverse childhood experiences, including
      various forms of child maltreatment, together with their mental health sequelae
      (eg, posttraumatic stress disorder, depression, dissociation) also contribute to
      adverse pregnancy outcomes (eg, preterm birth, low birth weight), poor postpartum
      mental health, and impaired or delayed bonding. Intergenerational patterns of
      maltreatment and mental health disorders have been reported that could be
      addressed in the childbearing year. Trauma-informed care is increasingly used in
      health care organizations and has the potential to assist in improving maternal
      and infant health. This article presents an overview of traumatic stress sequelae
      of childhood maltreatment and adversity, the impact of traumatic stress on
      childbearing, and technical assistance that is available from the National Center
      for Trauma-Informed Care (NCTIC) before articulating some steps to
      conceptualizing and implementing trauma-informed care into midwifery and other
      maternity care practices.

PMID- 29193615
TI  - President of the Gesellschaft Deutscher Chemiker: M. Urmann / Paul Karrer Medal:
      H. Waldmann / KCS-Wiley Young Chemist Award: Y. Lee and D.-H. Ko.

PMID- 29193614
TI  - Total Synthesis of (6R,10R,13R,14R,16R,17R,19S,20R,21R,24S,
      25S,28S,30S,32R,33R,34R,36S,37S,39R)-Azaspiracid-3 Reveals Non-Identity with the
      Natural Product.
AB  - A convergent and stereoselective total synthesis of the previously assigned
      structure of azaspiracid-3 has been achieved by a late-stage Nozaki-Hiyama-Kishi
      coupling to form the C21-C22 bond with the C20 configuration unambiguously
      established from l-(+)-tartaric acid. Postcoupling steps involved oxidation to an
      ynone, modified Stryker reduction of the alkyne, global deprotection, and
      oxidation of the resulting C1 primary alcohol to the carboxylic acid. The
      synthetic product matched naturally occurring azaspiracid-3 by mass spectrometry,
      but differed both chromatographically and spectroscopically.

PMID- 29193616
TI  - Uncatalyzed, Regioselective Oxidation of Saturated Hydrocarbons in an Ambient
      Corona Discharge.
AB  - Atmospheric pressure chemical ionization (APCI) in air or in nitrogen with just
      traces of oxygen is shown to yield regioselective oxidation, dehydrogenation, and
      fragmentation of alkanes. Ozone is produced from ambient oxygen in situ and is
      responsible for the observed ion chemistry, which includes partial oxidation to
      ketones and C-C cleavage to give aldehydes. The mechanism of oxidation is
      explored and relationships between ionic species produced from individual alkanes
      are established. Unusually, dehydrogenation occurs by water loss. Competitive
      incorporation into the hydrocarbon chain of nitrogen versus oxygen as a mode of
      ionization is also demonstrated.

PMID- 29193617
TI  - Clinical and molecular characterization of an emerging chromosome 22q13.31
      microdeletion syndrome.
AB  - Microdeletion of chromosome 22q13.31 is a very rare condition. Fourteen patients
      have been annotated in public databases but, to date, a clinical comparison has
      not been done and, consequently, a specific phenotype has not been delineated
      yet. We describe a patient showing neurodevelopmental disorders, dysmorphic
      features, and multiple congenital anomalies in which SNP array analysis revealed
      an interstitial 3.15 Mb de novo microdeletion in the 22q13.31 region encompassing
      21 RefSeq genes and seven non-coding microRNAs. To perform an accurate phenotype
      characterization, clinical features observed in previously reported cases of
      22q13.31 microdeletions were reviewed and compared to those observed in our
      patient. To the best of our knowledge, this is the first time that a comparison
      between patients carrying overlapping 22q13.31 deletions has been done. This
      comparison allowed us to identify a distinct spectrum of clinical manifestations
      suggesting that patients with a de novo interstitial microdeletion involving
      22q13.31 have an emerging syndrome characterized by developmental
      delay/intellectual disability, speech delay/language disorders, behavioral
      problems, hypotonia, urogenital, and hands/feet anomalies. The microdeletion
      identified in our patient is the smallest reported so far and, for this reason,
      useful to perform a detailed genotype-phenotype correlation. In particular, we
      propose the CELSR1, ATXN10, FBLN1, and UPK3A as candidate genes in the onset of
      the main clinical features of this contiguous gene syndrome. Thus, the patient
      reported here broadens our knowledge of the phenotypic consequences of 22q13.31
      microdeletions facilitating genotype-phenotype correlations. Additional cases are
      needed to corroborate our hypothesis and confirm genotype-phenotype correlations
      of this emerging syndrome.

PMID- 29193618
TI  - Distribution of ABO/Rh blood groups and their association with hepatitis B virus
      infection in 3.8 million Chinese adults: A population-based cross-sectional
      study.
AB  - ABO and Rh blood groups play a vital role in blood transfusion safety and
      clinical practice and are thought to be linked with disease susceptibility. The
      results from previous studies that focused on the association between blood
      groups and HBV infection remain controversial. China has the world's largest
      burden of HBV infection. We assessed the distribution of ABO/Rh blood groups in
      Chinese adults and examined the association between these groups and HBV
      infection. We did a nationwide cross-sectional study using data from a physical
      check-up programme from 31 provinces examined between 2010 and 2012. ELISA was
      used to test for HBsAg in serologic samples. Multivariable logistic regression
      was used to estimate aOR of the association between ABO and Rh blood groups and
      HBV infection. Among 3 827 125 participants, the proportion of participants with
      blood group A was highest (30.54%), followed by O (30.37%), B (29.42%) and AB
      (9.66%). A total of 38 907 (1.02%) were Rh-D negative. The prevalence of HBsAg in
      blood groups O, A, B and AB were 6.34%, 5.55%, 5.18% and 5.06%, respectively.
      HBsAg prevalence was 5.65% in Rh-D-positive and 3.96% in Rh-D-negative
      participants. After controlling for other potential risk factors, multivariate
      models showed that participants with blood group O (adjusted OR = 1.22, 95% CI:
      1.20-1.25) were at higher risk of HBV infection compared with group AB. Rh-D
      positive participants (adjusted OR = 1.44, 95% CI: 1.37-1.52) were at higher risk
      of HBV infection than Rh-D-negative participants. The associations between ABO/Rh
      blood groups and HBV infection were similar in subgroup analysis. The proportions
      of O, A, B and AB blood groups were approximately 3:3:3:1, and nearly 1 in 100
      people was Rh-D negative among Chinese adults. Blood group O and Rh-D positivity
      were both associated with increased HBV infection. The risk of HBV infection and
      blood safety should be taken into consideration in clinical practice, especially
      when transfusing those with blood group O. Awareness and prevention of HBV
      infection is of particular importance for individuals with blood group O.

PMID- 29193619
TI  - Crystal-Field Tuning of Photoluminescence in Two-Dimensional Materials with
      Embedded Lanthanide Ions.
AB  - Lanthanide (Ln) group elements have been attracting considerable attention owing
      to the distinct optical properties. The crystal-field surroundings of Ln ions in
      the host materials can determine their energy level splitting, which is of vital
      importance to tailor their optical properties. 2D MoS2 single crystals were
      utilized as the host material to embed Eu3+ and energy-level splitting was
      achieved for tuning its photoluminescence (PL). The high anisotropy of the 2D
      host materials makes them distort the degenerate orbitals of the Ln ions more
      efficiently than the symmetrical bulk host materials. A significant red-shift of
      the PL peak for Eu3+ was observed. The strategy for tailoring the energy level
      splitting of Ln ions by the highly designable 2D material crystal field provides
      a new method to extend their optical properties.

PMID- 29193620
TI  - Morphometric study of adipocytes on breast cancer by means of photonic microscopy
      and image analysis.
AB  - Worldwide, breast cancer (BrCa) is currently the leading cause of deaths
      associated to malignant lesions in adult women. Given that some studies have
      mentioned that peritumoral adipocytes may contribute to breast carcinogenesis,
      present work sought to quantitative evaluate the morphometry of these cells in a
      group of adult women. Three thousand six hundred sixty four breast adipocytes,
      that came from biopsies of a group of adult females with different types of
      breast carcinomas (ductal, lobular, and mixed) and one with normal tissues, were
      evaluated through an image analysis (IA) process regarding six morphometric
      descriptors: area (A), perimeter (P), Feret diameter (FD ), aspect ratio (AR),
      roundness factor (RF), and fractal dimension of cellular contour (FDC ). Data
      showed that the adipocytes of the normal tissues group were bigger (A: 3398 +/-
      2331 um2 , P: 239 +/- 83 um, and FD : 79.9 +/- 24.5 um) than those from BrCa
      samples (A: 2860 +/- 1933 um2 , P: 214 +/- 66 um, and FD : 73.2 +/- 22.5 um), and
      presented a more irregular contour (FDC of 1.370 +/- 0.037 for normal group and
      of 1.335 +/- 0.049 for the oncologic one). Moreover, it could be accounted that
      adipocytes of mixed carcinomas were largest (FD : 75.1 +/- 22.4 um) than those of
      lobular lesions (FD : 61.6 +/- 22.6 um), while the adipocytes of ductal
      carcinomas were the most oval (AR: 1.421 +/- 0.524) and roughest (FDC : 1.324 +/-
      0.050) cells. IA results suggest that BrCa lesions can be categorized through a
      quantitative morphometric evaluation of peritumoral adipocytes. These findings
      could let the development of an analytical tool to help the Pathologist to
      enhance the accuracy of the oncologic diagnose.

PMID- 29193622
TI  - Erratum.

PMID- 29193621
TI  - Review of the association between retinal microvascular characteristics and eye
      disease.
AB  - Computerized retinal imaging technologies enable the static and dynamic
      measurement of a range of retinal microvascular parameters. Large population
      based studies have reported associations between these microvascular indices and
      various ophthalmic diseases including diabetes, age-related macular degeneration,
      retinal artery embolism, retinal vein occlusion, glaucoma and non-glaucomatous
      optic neuropathies. Increasingly, sophisticated imaging and analysis techniques
      have the potential to provide relevant clinical information regarding disease
      risk and progression; however, further studies are required to verify
      associations and strengthen the predictive power of these techniques. We
      summarize the current state of knowledge regarding retinal microvascular
      characteristics and eye disease.

PMID- 29193623
TI  - Cognitive and behavioral phenotype of children with pseudohypoparathyroidism type
      1A.
AB  - Pseudohypoparathyroidism 1A (PHP1A) is a rare, genetic disorder. Most patients
      with PHP1A have cognitive impairment but this has not been systematically
      studied. We hypothesized that children with PHP1A would have lower intelligent
      quotient (IQ) scores than controls. To evaluate cognition and behavior, we
      prospectively enrolled children with PHP1A, one unaffected sibling (when
      available) and controls matched on BMI/age/gender/race. Evaluations included
      cognitive and executive function testing. Parents completed questionnaires on
      behavior and executive function. We enrolled 16 patients with PHP1A, 8 unaffected
      siblings, and 15 controls. Results are presented as mean (SD). The PHP1A group
      had a composite IQ of 85.9 (17.2); 25% had a composite IQ < -2 SD. The PHP1A
      group had significantly lower IQs than matched controls (composite IQ -17.3,
      95%CI -28.1 to -6.5, p < 0.01) and unaffected siblings (composite IQ -21.5, 95%CI
      -33.9 to -9.1, p < 0.01). Special education services were utilized for 93% of the
      patients with PHP1A. Deficits were observed in executive function and parents
      reported delayed adaptive behavior skills and increased rates of attention
      deficit hyperactivity disorder. In conclusion, children with PHP1A have lower
      intelligence quotient scores, poorer executive function, delayed adaptive
      behavior skills, and increased behavior problems.

PMID- 29193624
TI  - Management of childhood psoriasis in France. A national survey among general
      practitioners, pediatricians, and dermatologists.
AB  - Psoriasis affects 0.5-2% of children. Severe forms required use of systemic
      treatments. Few studies are published on efficiency and tolerance of systemic
      treatments in children. We conducted a survey in France to better understand
      management of children with psoriasis. A survey on childhood psoriasis management
      was sent by e-mail to GPs, pediatricians, and dermatologists. The survey included
      384 physicians. Respectively 53.1%, 49.8%, and 83.3% of GPs, pediatricians, and
      dermatologists declare to have seen at least one child with psoriasis during the
      3 previous months. Less than 5% of GPs and pediatricians used severity score
      versus 23.7% of dermatologists. If most of physicians declare to use local
      treatments, less than 5% of GPs and pediatricians used systemic treatments. 32.4%
      of dermatologists declared to use at least one systemic treatment, but only 2.9%
      to use the 4 systemic treatments available in France. This survey shows that only
      half of GPs and pediatricians see children with psoriasis, but most of
      dermatologists. However, the management of severe forms seems limited by the
      underuse of severity scores and systemic treatments. These results should
      stimulate dermatology societies to promote prospective studies and guidelines in
      young populations with psoriasis.

PMID- 29193625
TI  - Agreement Between Actigraphy and Diary-Recorded Measures of Sleep in Children
      With Epilepsy.
AB  - PURPOSE: To describe sleep patterns in young children with epilepsy and to
      examine levels of agreement between measurements derived from actigraphy and
      diary recordings. DESIGN: Cross-sectional study. METHODS: Eighty-nine toddlers
      and preschool-aged children with epilepsy wore an actigraph on their wrists for 7
      consecutive days. Parents and caregivers maintained a concurrent sleep diary
      while the child was wearing the monitor. Levels of agreement between actigraphy
      and diary recordings were examined using the Bland and Altman method separately
      for all recording days, weekdays, and weekends. FINDINGS: Discrepancies between
      actigraphy-derived and diary-documented sleep onset, sleep offset, actual sleep
      at night, wake after sleep onset, and daytime sleep were +/-35, +/-15, +/-82, +/
      70, and +/-29 min, respectively. Differences between actigraphy and diary-derived
      sleep variables were consistently greater for weekends than for weekdays.
      Discrepancies between actigraphy and diary-derived actual sleep at night were
      significantly greater for children who slept alone than for those who co-slept
      with a parent. CONCLUSIONS: Our study demonstrates an acceptable agreement
      between actigraphy and diary recordings for sleep onset, sleep offset, and
      daytime sleep, but insufficient agreement for actual sleep at night and wake
      after sleep onset, with parents of children sleeping alone more likely to
      misestimate child sleep behaviors. Deviation of weekend sleep from weekdays
      further decreased the accuracy of parental sleep estimates and increased the
      discrepancies between actigraphy and diary. CLINICAL RELEVANCE: Sleep in children
      with epilepsy assessed using diary recordings alone could be misleading, and
      actigraphy should be preferred over diaries when resources are available.

PMID- 29193626
TI  - Psychosocial work environment within psychiatric inpatient care in Sweden:
      Violence, stress, and value incongruence among nursing staff.

PMID- 29193627
TI  - A Vinyl Sulfone-Based Fluorogenic Probe Capable of Selective Labeling of PHGDH in
      Live Mammalian Cells.
AB  - Chemical probes are powerful tools for interrogating small molecule-target
      interactions. With additional fluorescence Turn-ON functionality, such probes
      might enable direct measurements of target engagement in live mammalian cells.
      DNS-pE (and its terminal alkyne-containing version DNS-pE2) is the first small
      molecule that can selectively label endogenous 3-phosphoglycerate dehydrogenase
      (PHGDH) from various mammalian cells. Endowed with an electrophilic vinyl sulfone
      moiety that possesses fluorescence-quenching properties, DNS-pE/DNS-pE2 became
      highly fluorescent only upon irreversible covalent modification of PHGDH. With an
      inhibitory property (in vitro Ki =7.4 MUm) comparable to that of known PHGDH
      inhibitors, our probes thus offer a promising approach to simultaneously image
      endogenous PHGDH activities and study its target engagement in live-cell
      settings.

PMID- 29193628
TI  - Integration of a faculty's ongoing research into an undergraduate laboratory
      teaching class in developmental biology.
AB  - Traditional developmental biology laboratory classes have utilized a number of
      different model organisms to allow students to be exposed to diverse biological
      phenomena in developing organisms. This traditional approach has mainly focused
      on the diverse morphological and anatomical descriptions of the developing
      organisms. However, modern developmental biology is focusing more on conserved
      genetic networks which are responsible for generating conserved body patterns in
      developing organisms. Therefore, it is necessary to develop a new pedagogical
      tool to educate undergraduate biology students in the laboratory class of
      developmental biology with the genetic principles which are responsible for
      generating and controlling the developing body patterns. A new undergraduate
      laboratory class for developmental biology was developed in order to offer
      students the opportunity to explore a wide range of experimental procedures, also
      incorporating the instructor's on-going research. Thereby the course can serve as
      a bridge between research and education by combining both into a single theme.
      The course design involves a sequence of exercises which can be easily adapted to
      the faculty's ongoing research. This style of laboratory coursework could be a
      transitional form between a regular laboratory course and a discovery-based
      laboratory course. (c) 2017 by The International Union of Biochemistry and
      Molecular Biology, 46(2):141-150, 2018.

PMID- 29193629
TI  - Relationship between the severity of cerebral white matter hyperintensities and
      sympathetic nervous activity in older adults.
AB  - AIM: White matter hyperintensities (WMH), visualized on brain magnetic resonance
      imaging, represent an abnormality related to the development of geriatric
      syndromes. Recently, it has been found that low sympathetic nervous activity
      might be associated with physical and cognitive dysfunction in older adults.
      Therefore, we investigated the relationship between the severity of cerebral WMH
      and sympathetic nervous activity, measured by the heart rate variability.
      METHODS: We carried out a cross-sectional study of 39 older patients. Holter
      recording was carried out for 30 min. From the RR intervals on the
      electrocardiogram, the standard deviation of the normal-to-normal intervals, the
      standard deviation of all normal-to-normal intervals in all the five segments of
      the entire recording, low frequency (LF), high frequency (HF) and LF/HF were
      calculated. In regard to the WMH, periventricular hyperintensities and deep white
      matter hyperintensities (DWMH) were rated according to the Fazekas
      classification. The WMH were also rated semiquantitatively according to the
      methods developed by Junque (periventricular hyperintensities) and de Groot
      (DWMH). RESULTS: The LF/HF showed significant negative correlations with the
      total and regional periventricular hyperintensities, as well as DWMH. Multiple
      regression analysis showed that the negative associations remained significant
      between the LF/HF and DWMH (total, temporal, occipital). Furthermore, fall risk
      index significantly correlated with the LF/HF, total and the occipital DWMH.
      CONCLUSIONS: The severity of the DWMH was associated with the LF/HF and the fall
      risk, one of the important geriatric syndromes, suggesting that WMH, sympathetic
      nervous dysfunction and geriatric syndrome are interrelated to each other.
      Geriatr Gerontol Int 2018; 18: 569-575.

PMID- 29193630
TI  - Cardiac function, A key component in evaluation for liver transplant.

PMID- 29193631
TI  - An audit of change in clinical practice: from oxygen-driven to air-driven
      nebulisers for prehospital patients with acute exacerbations of chronic
      obstructive pulmonary disease (AECOPD).
AB  - BACKGROUND: In developed countries, ambulances normally carry oxygen cylinders,
      but not compressed air. Treatment of acute exacerbations of chronic obstructive
      pulmonary disease (AECOPD) with oxygen-driven nebulisers can result in
      hypercapnia and acidosis. Attempts to avoid this have involved interrupted
      administration of oxygen. However, small battery-powered air nebulisers are now
      available. This study aims to compare the prehospital oxygen saturations and
      treatment of patients suffering from AECOPD before and after the introduction of
      air nebulisers. METHODS: The oxygen saturations and treatment of 200 AECOPD
      patients before and 200 AECOPD patients after the introduction of air nebulisers
      were compared. Compliance with a target saturation of 88-92% was calculated.
      RESULTS: The median final oxygen saturation was lower for the post-intervention
      category (94%) than the pre-intervention category (96%). There was an increase in
      air nebuliser use from 0 to 56% (P < 0.001) and a decrease in oxygen use from 100
      to 71.5% (P < 0.001). There was a numerical increase in the proportion of
      patients arriving at hospital with oxygen saturations of 88-92% following
      introduction of the air nebulisers (24 vs 16.5%) and a decrease in patients
      arriving with high saturations (67.5 vs 76.5%). The likelihood of achieving the
      target oxygen saturations following introduction of air nebulisers increased
      (odds ratio 1.598; 95% confidence interval 0.974, 2.621). CONCLUSION: The
      introduction of prehospital air nebulisers resulted in a reduction in oxygen
      therapy in patients with AECOPD and a lower median prehospital oxygen saturation.
      This study supports the use of air nebulisers in the prehospital setting.

PMID- 29193632
TI  - Lip repositioning for the treatment of excess gingival display: A systematic
      review.
AB  - BACKGROUND: Lip repositioning is a conservative surgical technique used to treat
      excess gingival display. An array of modifications has been introduced to the
      technique over time and as studies show the technique and its modifications to be
      successful, there is little standardized information for clinicians to make
      informed decisions when choosing this technique for the treatment of patients
      with excessive gingival display (EGD). OBJECTIVES: To review the current
      literature on the topic of lip repositioning for the treatment of excessive EGD,
      exploring outcome, and result longevity. METHODS: A structured systematic search
      was carried out using the Ovid database and Web of Science to identify published
      studies on lip repositioning technique. Search was restricted to studies in the
      English language, describing a surgical intervention. Case reports were included
      as the number of published studies was limited. RESULTS: The electronic search
      identified 93 articles, hand search identified 1 article, and reference search
      identified 1 article. After excluding duplicates and screening articles, a total
      of 22 articles met the inclusion criteria. An estimated mean improvement of 3.4
      mm (95% confidence interval, 3.0-3.8 mm) was found possible with lip
      repositioning. Data analysis was performed using only 4 studies, amounting to a
      total of 33 patients. Potential risk of bias was identified in some of the
      studies included. CONCLUSIONS: Despite the limited available studies on lip
      repositioning, an estimated mean improvement of 3.4 mm was found to be possible
      with surgical lip repositioning, suggesting that the technique could be used
      successfully to treat EGD. However, more studies are necessary to properly
      evaluate the treatment approach and stability of the technique. CLINICAL
      SIGNIFICANCE: Recently, the demand for esthetics has significantly increased,
      driven by increased patient awareness and the search for an ideal smile. Creating
      the perfect smile is an intricate process that requires a multidisciplinary
      approach, with careful consideration of the lips and the gingival outline. Excess
      gingival display results in an unaesthetic smile, lip repositioning offers a
      comparatively simple solution for this problem. While the quality literature on
      this topic is limited statistical analysis of collected studies show that an
      estimated mean improvement of 3.4 mm can be achieved with surgical lip
      repositioning.

PMID- 29193633
TI  - Evidence-based dentistry can effectively be taught to dental care professional
      students - A mixed methods study.
AB  - BACKGROUND: Little research exists in the teaching of evidence-based dentistry
      (EBD) to students in the fields of dental hygiene, dental nursing and orthodontic
      therapy. This study aims to analyse the effect of a 1-day EBD programme on
      knowledge and confidence whilst also gaining insight into students' experience of
      the intervention. METHOD: A mixed methods study was utilised with explanatory
      sequential design. The population consisted of dental hygiene (DH), dental
      nursing (DN) and orthodontic therapy (OT) students (N = 44). The intervention
      consisted of a 1-day active learning EBD programme, delivered via group projects
      and lectures. In the initial quantitative phase, a standardised questionnaire pre
      and post -intervention measured changes in confidence for all participants,
      whilst change in knowledge was measured for DH and OT students only. Following
      this, focus groups were scheduled for all members of each discipline 3 months
      post-intervention for DN and 2 months post-intervention for DH and OT students.
      Semi-structured focus group schedules were drawn up, and groups organised
      according to the outcomes of quantitative data analysis. Qualitative results were
      analysed using a deductive adaptation of Burnard's thematic content analysis.
      RESULTS: Forty-two students took part (94.45%) in this study. Median knowledge
      scores increased from zero to two of five (P < .001), whilst median confidence
      score doubled from four to eight of eight (P < .001). Results of thematic content
      analysis were coincident with quantitative results; however, it also provided
      constructive feedback regarding design and content of the course. CONCLUSIONS: A
      1-day bespoke programme in EBD increased students' confidence and knowledge in
      EBD skills. However, the findings further suggest that two successive half-day
      training sessions instead of one full-day training, tied in with coursework that
      requires the application of the acquired skills, may increase the learning
      experience further.

PMID- 29193634
TI  - Comparative study on the liquid chromatographic enantioseparation of cyclic beta
      amino acids and the related cyclic beta-aminohydroxamic acids on Cinchona
      alkaloid-based zwitterionic chiral stationary phases.
AB  - The enantiomeric pairs of cis and trans stereoisomers of cyclic beta
      aminohydroxamic acids and their related cis and trans cyclic beta-amino acids
      containing two chiral centers were directly separated on four structurally
      related chiral stationary phases derived from quinine and quinidine modified with
      (R,R)- and (S,S)-aminocyclohexanesulfonic acids. Applying these zwitterionic ion
      exchangers as chiral selectors, the effects of the composition of the bulk
      solvent, the acid and base additives, the structures of the analytes, and
      temperature on the enantioresolution were investigated. To study the effects of
      temperature and obtain thermodynamic parameters, experiments were carried out at
      constant mobile phase compositions in the temperature range 5-50 degrees C. The
      differences in the changes in standard enthalpy Delta(DeltaH degrees ), entropy
      Delta(DeltaS degrees ), and free energy Delta(DeltaG degrees ) were calculated
      from the linear van't Hoff plots derived from the ln alpha versus 1/T curves in
      the studied temperature range. Results thus obtained indicated enthalpy-driven
      separations in all cases. The sequence of elution of the enantiomers was
      determined and found to be reversed when ZWIX(-)TM was changed to ZWIX(+)TM or
      ZWIX(-A) to ZWIX(+A).

PMID- 29193636
TI  - Depression, Perceived Health, and Right-of-Return Hopefulness of Palestinian
      Refugees.
AB  - PURPOSE: Displacement is traumatic and often an unwanted social change that can
      lead to a loss of identity and socioeconomic, physical, and psychological
      livelihood. The purpose of the study was to describe the association of perceived
      health and right-of-return hopefulness to depressive symptom severity in
      Palestinian refugees, taking into consideration gender and poverty. DESIGN: The
      descriptive, correlational study was framed within a socioecological lens. Data
      collection occurred between October 2015 and November 2015 in Amman, Jordan,
      which hosts the most Palestinian refugees in the world. The participants in the
      sample (N = 177) had a mean age of 36.9 years. METHODS: Participants responded to
      the Patient Health Questionnaire for depressive symptom severity, the RAND-36
      perceived health item, and a statement about hopefulness to return to Palestine.
      Descriptive, correlation, and logistic and linear regression analyses were
      computed. FINDINGS: Results showed that 43% of participants had moderate to
      severe depressive symptoms, 42% lived in poverty, and 20% had fair or poor
      health; yet, 60% were hopeful about returning to Palestine. Participants who had
      better perceived health and right-of-return hopefulness were less likely to have
      symptoms of major depression. Perceived health was the only factor-not gender,
      poverty, or right-of-return hopefulness-that explained the variance in depressive
      symptoms. CONCLUSIONS: Palestinian adult refugees in Jordan exhibited symptoms of
      major depression that were associated with poorer perceived health and less
      hopefulness about repatriation to Palestine. CLINICAL RELEVANCE: Nurses with
      community or mental health specialization can play a major role by systematically
      screening refugees for depression using worldwide, evidence-based tools and by
      advocating for policies that can improve the health and living conditions of
      refugees.

PMID- 29193635
TI  - Inactivation of AMMECR1 is associated with growth, bone, and heart alterations.
AB  - We report five individuals with loss-of-function of the X-linked AMMECR1: a girl
      with a balanced X-autosome translocation and inactivation of the normal X
      chromosome; two boys with maternally inherited and de novo nonsense variants; and
      two half-brothers with maternally inherited microdeletion variants. They present
      with short stature, cardiac and skeletal abnormalities, and hearing loss.
      Variants of unknown significance in AMMECR1 in four male patients from two
      families with partially overlapping phenotypes were previously reported. AMMECR1
      is coexpressed with genes implicated in cell cycle regulation, five of which were
      previously associated with growth and bone alterations. Our knockdown of the
      zebrafish orthologous gene resulted in phenotypes reminiscent of patients'
      features. The increased transcript and encoded protein levels of AMMECR1L, an
      AMMECR1 paralog, in the t(X;9) patient's cells indicate a possible partial
      compensatory mechanism. AMMECR1 and AMMECR1L proteins dimerize and localize to
      the nucleus as suggested by their nucleic acid-binding RAGNYA folds. Our results
      suggest that AMMECR1 is potentially involved in cell cycle control and linked to
      a new syndrome with growth, bone, heart, and kidney alterations with or without
      elliptocytosis.

PMID- 29193637
TI  - Use of adapalene in alopecia areata: Efficacy and safety of mometasone furoate
      0.1% cream versus combination of mometasone furoate 0.1% cream and adapalene 0.1%
      gel in alopecia areata.
AB  - Alopecia areata (AA) is an autoimmune disease characterized by non-cicatricial
      hair loss. No definitive therapy currently exists for AA. To compared the
      efficacy and safety of the mometasone furoate 0.1% cream alone with the
      mometasone furoate 0.1% cream plus adapalene 0.1% gel in treatment of AA. Twenty
      patients with AA and with mean age of 27.4 +/- 9.2 years were enrolled. Patches
      with a diameter of < 5 cm were treated with mometasone furate 0.1% cream (M), and
      patches with a diameter of >=5 cm were treated with mometasone furate 0.1% cream
      plus adapalene 0.1% gel (M + D) for a period of 12 weeks. Hair regrowth was
      evaluated using a Re-growth score (RGS). Mean RGSs of M + D group were higher
      than M group for 4th week (2.60 vs. 1.45); 8th week (3.85 vs. 2.40) and 12th week
      (4.40 vs. 3.30). Mean percentages of hair re-growth in M + D group were
      statistically higher than M group for 4th (50.2% vs. 23.5%), 8th (78.5% vs.
      50.7%), and 12th week (90.5% vs. 71%). Study revealed the efficacy and safety of
      adapalene and mometasone furoate combination in AA. Adapalene can be used as a
      new therapeutic modality in AA.

PMID- 29193638
TI  - Delayed diagnosis of atrial fibrillation after first-ever stroke increases
      recurrent stroke risk: a 5-year nationwide follow-up study.
AB  - BACKGROUND: Delayed detection of atrial fibrillation (AF) is common in patients
      with stroke. However, it is not well known whether delayed identification of AF
      in patients with stroke affects the prognosis of patients. AIMS: To evaluate the
      association between the timing of AF diagnosis after stroke and clinical
      outcomes. METHODS: We identified a cohort of all patients admitted with a primary
      diagnosis of first-ever ischaemic stroke, which was categorised into three
      groups, namely, non-AF, AF presenting with stroke and delayed AF diagnosis
      groups. The study patients were individually followed for 5 years to evaluate the
      occurrence of recurrent stroke and death. RESULTS: In total, 17 399 patients were
      hospitalised with first-ever ischemic stroke, of whom 16 261 constituted the non
      AF group, 907 the AF presenting with stroke group and 231 the delayed AF
      diagnosis group. During the 5-year follow up, 2773 (17.1%), 175 (19.3%) and 68
      (29.4%) patients in the non-AF, AF presenting with stroke and delayed AF
      diagnosis groups, respectively, were hospitalised for recurrent stroke. The
      delayed AF diagnosis group exhibited a 1.57-times higher risk of recurrent stroke
      than the AF presenting with stroke group, after adjustment for the CHA2DS2-VASc
      scores (adjusted hazard ratio (HR): 1.57; 95% confidence interval (CI) = 1.19
      2.08; P = 0.002). In addition, delayed diagnosis of AF significantly increased
      the risk of recurrent stroke in men, but not in women, after adjustment for the
      CHA2DS2-VASc scores. CONCLUSION: Delayed diagnosis of AF after stroke increased
      the risk of recurrent stroke, particularly in men.

PMID- 29193639
TI  - Oligonephronia and Wolf-Hirschhorn syndrome: A further observation.
AB  - Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder caused by a partial
      deletion of chromosome 4 (4p16.3p16.2). We describe a case of a male 9 years old
      children with WHS proteinuria and hypertension. Laboratory data showed creatinine
      1.05 mg/dl, GFR 65.9 ml/min/1.73 m2 , cholesterol 280 mg/dl, triglyceride 125
      mg/dl with electrolytes in the normal range. Urine collection showed protein 2.72
      g/L with a urine protein/creatinine ratio (UP /UCr ratio) of 4.2 and diuresis of
      1,100 ml. Renal ultrasound showed reduced kidney dimensions with diffusely
      hyperechogenic cortex and poorly visualized pyramids. Renal biopsy showed
      oligonephronia with focal segmental glomerulosclerosis associated with initial
      tubulointerstitial sclerotic atrophy. The child began therapy with Angiotensin
      converting enzyme inhibitors (ACE-inhibitors) to reduce proteinuria and
      progression of chronic kidney disease. In the literature the anomalies of number
      of glomeruli oligonephronia and oligomeganephronia (OMN) are described in two
      forms, one without any associated anomalies, sporadic, and solitary and the other
      with one or more anomalies. Our review of the literature shows that the
      pathogenesis of this anomaly is unknown but the role of chromosome 4 is very
      relevant. Many cases of OMN are associated with anomalies on this chromosome, in
      the literature cases series we observed this association in 14/48 cases (29.2%)
      and in 7 of these 14 cases with WHS. Our case and the review of literature
      demonstrate how periodic urinalysis and renal ultrasound monitoring is
      recommended in patients affected by WHS and the renal biopsy must be performed
      when there is the onset of proteinuria.

PMID- 29193640
TI  - Rise of the zombie institution, the failure of mental health nursing leadership,
      and mental health nursing as a zombie category.
AB  - In this paper, we propose that mental health nursing has become a zombie
      category, at least in the Australian context. Mental health nursing is a concept
      that has lost any real explanatory or conceptual power, yet nevertheless persists
      in public discourse and the collective imagination. In recent decades, powerful
      forces have contributed to the zombification of the mental health nursing
      workforce and the academy. An increase in medical hegemony, the ascendancy of
      allied health in mental health service provision, the need for uncritical and
      servile workers, protocol-driven work practices, and a failure of leadership to
      mobilize any substantial resistance to these trends have enabled the infection to
      spread. The recognition of zombification, active resistance against the forces
      that conspire to cause it, and the cultivation of genuine conscientious critical
      thought and debate offer the only hope of survival of mental health nursing as a
      thriving specialty.

PMID- 29193641
TI  - Comparison of passive and active leisure activities and life satisfaction with
      aging.
AB  - AIM: Many older adults face limitations to participating in active leisure
      activities as a result of their physical constraints from aging. Passive leisure
      activities become alternative leisure activities for older adults as a result of
      limited physical capacity. The present study sought to determine whether there
      exists a difference in the frequency of participation in passive and active
      leisure activities, and the effect of participation in passive and active leisure
      activities on the life satisfaction level of old adults. METHODS: A total of 460
      participants aged 60-95 years were randomly selected from 21 sites in the USA.
      The Life Satisfaction Index - Z and the Meaningful Activity Participation
      Assessment were analyzed to examine older adults' life satisfaction and frequency
      of active or passive activities. RESULTS: The results showed that participation
      in passive leisure activities, such reading, talking on the telephone and
      watching TV/listening to the radio, is more frequent among older adults (P =
      0.000). The regression coefficient found that club/organization or volunteering
      (P = 0.008), homemaking/maintenance (P = 0.017) and traveling (P = 0.017) for
      active leisure activities were statistically significant predictors of Life
      Satisfaction Index - Z for older adults. CONCLUSIONS: The current study shows
      that older adults spent much more times participating in passive leisure
      activities, such as radio/watching TV, talking on the phone and reading. The
      result also showed that active leisure activities, such as club/organization or
      volunteering, home making/maintenance and traveling, were significant predictors
      of life satisfaction for older adults controlling for covariates. The current
      study suggests marketing and programming plans to overcome the constraints that
      influence older adults' life satisfaction. Geriatr Gerontol Int 2018; 18: 380
      386.

PMID- 29193642
TI  - Lessons for the monitoring of safety in clinical trials.

PMID- 29193643
TI  - Performance metrics for guidance active constraints in surgical robotics.
AB  - Active constraint (AC)/virtual fixture (VF) is among the most popular approaches
      towards the shared execution of subtasks by the surgeon and robotic systems. As
      more possibilities appear for the implementation of ACs in surgical scenarios,
      the need to introduce methods that guarantee a safe and intuitive user
      interaction increases. The presence of the human in the loop adds a layer of
      interactivity and adaptability that renders the assessment of such methods non
      trivial. In most works, guidance ACs have been evaluated mainly in terms of
      enhancement of accuracy and completion time with little regard for other aspects
      such as human factors, even though the continuous engagement of these methods can
      considerably degrade the user experience. This paper proposes a set of
      performance metrics and considerations that can help evaluate guidance ACs with
      reference to accuracy enhancement, force characteristics and subjective aspects.
      The use of these metrics is demonstrated through two sets of experiments on 12
      surgeons and 6 inexperienced users.

PMID- 29193644
TI  - The use of needle holders in CTF guided biopsies as a dose reduction tool.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of needle holders
      in reducing staff hand exposure during biopsies guided by computed tomography
      fluoroscopy (CTF), through the analysis of data acquired during a detailed
      monitoring study, undertaken in parallel with an ongoing optimization process to
      reduce hand irradiation. METHODS: Hand monitoring was performed with 11 extremity
      detectors, two per finger (base and tip) and one on the back of the wrist, for
      the left (dominant) hand, during two series of biopsies with comparable
      characteristics. The first series (47 biopsies) were performed with only quick
      check method (QC) and occasional side-handle (SH) manipulation of the needle. The
      second series (63 biopsies) were performed after introducing needle holders (NH)
      in the course of an optimization process. RESULTS: Choice of technique (QC, QC +
      NH, QC + SH) by the interventional radiologist (IR) was related to biopsy
      difficulty. Measured hand exposure was low (< 1 mSv) for all QC-only procedures,
      and for most of the QC + NH procedures. Occasional side-handle manipulation still
      occurred during challenging biopsies, so that 8% of biopsies in the second series
      accounted for ~70% of total fingertip dose (~90 mSv). The methodology used
      allowed a detailed insight into the dose reduction achievable with needle holders
      during real procedures, without the limitations of phantom measurements.
      CONCLUSIONS: Needle holders proved effective in reducing mean hand exposure
      during clinical procedures where real-time manipulation was necessary. Occasional
      side-handle manipulation was found to contribute disproportionately to hand
      exposure. This highlights the importance of individual hand monitoring during CTF
      guided procedures.

PMID- 29193645
TI  - MAPK inhibitors induce serine peptidase inhibitor Kazal type 1 (SPINK1) secretion
      in BRAF V600E-mutant colorectal adenocarcinoma.
AB  - The mitogen-activated protein kinase (MAPK) pathway plays a central role in
      colorectal cancers (CRC). In particular, BRAF V600E-mutant tumors, which
      represent around 10% of CRCs, are refractory to current therapies. Overexpression
      and secretion of serine peptidase inhibitor Kazal type 1 (SPINK1) are observed in
      around 50% of CRCs, and its serum level can be used as a biomarker for poor
      prognosis. Utilizing a recently developed extendable blocking probe assay, we
      analyzed the BRAF mutation status in a CRC patient cohort (N = 571) using tissue
      derived RNA as the starting material. From the same RNA samples, we measured the
      relative SPINK1 expression levels using a quantitative real-time PCR method.
      Expression of mutant BRAF V600E correlated with poor prognosis, as did low
      expression of SPINK1 mRNA. Further, BRAF V600E correlated negatively with SPINK1
      levels. In order to investigate the effect of MAPK pathway-targeted therapies on
      SPINK1 secretion, we conducted in vitro studies using both wild-type and V600E
      CRC cell lines. BRAF inhibitor vemurafenib, and subsequent MAPK pathway
      inhibitors trametinib and SCH772984, significantly increased SPINK1 secretion in
      V600E CRC cell lines Colo205 and HT-29 with a concomitant decrease in trypsin-1
      and -2 secretion. Notably, no SPINK1 increase or trypsin-1 decrease was observed
      in BRAF wild-type CRC cell line Caco-2 in response to MAPK pathway inhibitors. In
      further mechanistic studies, we observed that only trametinib was able to
      diminish completely both MEK and ERK phosphorylation in the V600E CRC cells.
      Furthermore, the key regulator of integrated stress response, activating
      transcription factor 4 (ATF-4), was downregulated both at mRNA and at protein
      level in response to trametinib treatment. In conclusion, these data suggest that
      sustained inhibition of not only MAPK pathway activation, but also ATF-4 and
      trypsin, might be beneficial in the therapy of BRAF V600E-mutant CRC and that
      SPINK1 levels may serve as an indicator of therapy response.

PMID- 29193646
TI  - Quantifying the hidden healthcare cost of diabetes mellitus in Australian
      hospital patients.
AB  - BACKGROUND: Diabetes mellitus in hospital inpatients is most commonly present as
      a comorbidity rather than as the primary diagnosis. In some hospitals, the
      prevalence of comorbid diabetes mellitus across all inpatients exceeds 30%, which
      could add to complexity of care and resource utilisation. However, whether and to
      what extent comorbid diabetes mellitus contributes indirectly to greater
      hospitalisation costs is ill-defined. AIM: To determine the attributable effect
      of comorbid diabetes mellitus on hospital resource utilisation in a General
      Internal Medical service in Melbourne, Australia. METHODS: We extracted data from
      a database of all General Internal Medical discharge episodes from July 2012 to
      June 2013. We fitted multivariable regression models to compare patients with
      diabetes mellitus to those without diabetes mellitus with respect to
      hospitalisation cost, length of stay, admissions per year and inpatient
      mortality. RESULTS: Of 4657 patients 1519 (33%) had diabetes mellitus, for whom
      average hospitalisation cost (AUD9910) was higher than those without diabetes
      mellitus (AUD7805). In multivariable analysis, this corresponded to a 1.22-fold
      (95% confidence interval (CI) 1.12-1.33, P < 0.001) higher cost. Mean length of
      stay for those with diabetes was 8.2 days versus 6.8 days for those without
      diabetes, with an adjusted 1.19-fold greater odds (95% CI 1.06-1.33, P = 0.001)
      of staying an additional day. Number of admissions and mortality were similar.
      CONCLUSION: Comorbid diabetes mellitus adds significantly to hospitalisation
      duration and costs in medical inpatients. Moreover, diabetes mellitus patients
      with chronic complications had a greater-still cost and hospitalisation duration
      compared to those without diabetes mellitus.

PMID- 29193647
TI  - The incidence, characteristics, management and outcomes of anaphylaxis in
      pregnancy: a population-based descriptive study.
AB  - OBJECTIVE: The aim of this study was to estimate the incidence of anaphylaxis in
      pregnancy and describe the management and outcomes in the UK. DESIGN: A
      population-based descriptive study using the UK Obstetric Surveillance System
      (UKOSS). SETTING: All consultant-led maternity units in the UK. POPULATION: All
      pregnant women who had anaphylaxis between 1 October 2012 and 30 September 2015.
      Anaphylaxis was defined as a severe, life-threatening generalised or systemic
      hypersensitivity reaction. METHODS: Prospective case notification using UKOSS.
      MAIN OUTCOME MEASURES: Maternal mortality, severe maternal morbidity, neonatal
      mortality and severe neonatal morbidity. RESULTS: There were 37 confirmed cases
      of anaphylaxis in pregnancy, giving an estimated incidence of 1.6 (95% CI: 1.1
      2.2) per 100 000 maternities. Four cases of anaphylaxis were in women with known
      penicillin allergies: two received co-amoxiclav and two cephalosporins. Twelve
      women had anaphylaxis following prophylactic use of antibiotics at the time of a
      caesarean delivery. Prophylactic use of antibiotics for Group B streptococcal
      infection accounted for anaphylaxis in one woman. Two women died (5%), 14 (38%)
      women were admitted to intensive care and seven women (19%) had one or more
      additional severe maternal morbidities, which included three haemorrhagic events,
      two cardiac arrests, one thrombotic event and one pneumonia. No infants died;
      however, in those infants whose mother had anaphylaxis before delivery (n = 18)
      there were seven (41%) neonatal intensive care unit admissions, three preterm
      births and one baby was cooled for neonatal encephalopathy. CONCLUSIONS:
      Anaphylaxis is a rare severe complication of pregnancy and frequently the result
      of a reaction to antibiotic administration. This study highlights the seriousness
      of the outcomes of this condition for the mother. The low incidence is reassuring
      given the large proportion of the pregnant population that receive prophylactic
      antibiotics during delivery. TWEETABLE ABSTRACT: Anaphylaxis is a rare severe
      complication of pregnancy and frequently the result of a reaction to antibiotic
      administration.

PMID- 29193648
TI  - The importance of trifluoromethyl pyridines in crop protection.
AB  - The pyridine ring, substituted by a trifluoromethyl substituent has been
      successfully incorporated into molecules with useful biological properties.
      During the period 1990 to September 2017, 14 crop protection products bearing a
      trifluoromethyl pyridine have been commercialized or proposed for an ISO common
      name, covering fungicides, herbicides, insecticides and nematicides. Chemical
      processes have been developed to provide trifluoromethyl pyridine intermediates,
      from non-fluorinated pyridine starting materials, at scale and with affordable
      costs of goods. These attractive starting materials were readily adopted by
      research chemists, and elaborated through simple chemical modifications into new
      active ingredients. In a second approach, substituted trifluoromethyl pyridine
      rings have been constructed from acyclic, trifluoromethyl starting materials,
      which again has served to identify new active ingredients. Molecular matched pair
      analysis reveals subtle, yet important differences in physicochemical and
      agronomic properties of trifluoromethyl pyridines compared with the phenyl
      analogues. This review focuses on the past 27 years, seeking to identify reasons
      behind the success of such research programmes, and inspire the search for new
      crop protection chemicals containing the trifluoromethyl pyridine ring. (c) 2017
      Society of Chemical Industry.

PMID- 29193649
TI  - Infantile hemangioma: pathogenesis and mechanisms of action of propranolol.
AB  - Infantile hemangioma (IH) is the most common benign tumor of childhood, with a
      prevalence of 4 % to 10 %. It is characterized by a proliferative rapid growth
      phase, which starts after a few weeks of life, followed by a slow regression
      phase. In IH cases that are potentially disfiguring or life-threatening (10 % to
      15 % of all cases), systemic therapy should be promptly initiated. Data source
      The present study reviews published scientific articles available in reliable
      electronic databases. Selected were all studies that evaluated the pathogenesis
      of IH and the mechanisms of action of propranolol. Conclusions The pathogenesis
      of IH has not been fully elucidated. Studies show that, in the proliferative
      phase of IH, there is an imbalance of angiogenic factors and an increase in the
      levels of vascular endothelial growth factor and matrix metalloproteinases 2 and
      9. In the regression phase, the levels of these factors decrease, whereas those
      of antiangiogenic factors, including tissue inhibitors of matrix
      metalloproteinases, increase. Since 2008, propranolol has become the drug of
      choice in the treatment of IH, targeting vascular tone, angiogenesis, and
      apoptosis. Current insights into the pathogenesis of IH allow for the development
      of new therapeutic strategies.

PMID- 29193650
TI  - Effect of characteristics of pharmacotherapy on non-adherence in chronic
      cardiovascular disease: A systematic review and meta-analysis of observational
      studies.
AB  - INTRODUCTION: Cardiovascular medications are effective in prevention of
      cardiovascular diseases (CVD); however, medication non-adherence contributes to
      morbidity and mortality. OBJECTIVE: This systematic review and meta-analysis aims
      to summarise the evidence regarding the relationship between characteristics of
      drug therapy (pharmacotherapy) and medication non-adherence in the CVD
      population. METHODS: Systematic searches in PubMed, LILACS, Academic Search and
      CINAHL databases for observational studies that enrolled adults with CVD were
      performed, from January 1960 to December 2015. The meta-analysis tested the
      association between characteristics of pharmacotherapy and self-reported
      medication non-adherence outcome, using a random effects model. To investigate
      heterogeneity, we performed subgroup analysis and sensitivity analysis. RESULTS:
      Twenty-four cross-sectional studies and 7 cohort studies were included in this
      review. Based on 31 studies including 27 441 participants, we performed meta
      analyses for all the characteristics of drug therapy that at least 2 studies
      evaluated, with a total of fourteen meta-analyses. The pooled results showed that
      studies which evaluate whether participants have insurance or another program
      that assists with medication costs, but not full coverage (OR = 0.63; 95% CI:
      0.53-0.74; P < .001; I2  = 0%, P = .938), and a dosing frequency of twice or more
      daily (OR = 1.38; 95% CI: 1.13-1.69; P < .001) were associated with non
      adherence. CONCLUSIONS AND RELEVANCE: The results of this review suggest that
      access to insurance or another program that assists with medication costs was a
      protection factor for non-adherence. On the other hand, a high frequency of
      dosing was a risk factor for non-adherence. Therefore, these characteristics of
      pharmacotherapy must be considered to improve medication adherence among CVD
      patients.

PMID- 29193651
TI  - Platelet-Facilitated Photothermal Therapy of Head and Neck Squamous Cell
      Carcinoma.
AB  - Here, we present a platelet-facilitated photothermal tumor therapy (PLT-PTT)
      strategy, in which PLTs act as carriers for targeted delivery of photothermal
      agents to tumor tissues and enhance the PTT effect. Gold nanorods (AuNRs) were
      first loaded into PLTs by electroporation and the resulting AuNR-loaded PLTs (PLT
      AuNRs) inherited long blood circulation and cancer targeting characteristics from
      PLTs and good photothermal property from AuNRs. Using a gene-knockout mouse
      model, we demonstrate that the administration of PLT-AuNRs and localizing laser
      irradiation could effectively inhibit the growth of head and neck squamous cell
      carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT
      AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a
      feedback manner, demonstrating the unique self-reinforcing characteristic of PLT
      PTT in cancer therapy.

PMID- 29193652
TI  - Decisions about aneuploidy screening: why women's reasons are important.

PMID- 29193653
TI  - Incidence and risk factors for deep surgical site infection after open reduction
      and internal fixation of closed tibial plateau fractures in adults.
AB  - This study aimed to investigate the incidence and risk factors of deep surgical
      site infection (DSSI) during hospitalisation after closed tibial plateau
      fractures treated with open reduction and internal fixation (ORIF). We performed
      this retrospective study at a university-affiliated hospital with an advanced
      trauma centre. The data of adult patients with closed tibial plateau fractures
      treated with ORIF from January 2012 to February 2017 were extracted from the
      electronic medical records. Demographics, injury-related and surgery-related
      variables of DSSI and non-DSSI groups were compared by univariate test.
      Multivariate logistic analysis models were used to investigate the independent
      risk factors. In total, 676 patients with complete data met the inclusion
      criteria and were included, and of them, 17 developed DSSI (2.51%) during
      hospitalisation. Approximately 60% (9/17) of DSSI was caused by Staphylococcus
      aureus. Compared to the non-DSSI group, DSSI patients had a significantly longer
      stay in hospital (25.8 vs 15.2 days). Independent risk factors of DSSI identified
      by multivariate analysis were higher BMI (>26.0) (OR, 1.58; 95% CI, 1.09 to 3.27;
      P = 0.032), prolonged surgical duration (>138 min) (OR, 4.26; 95% CI, 1.54 to
      11.19; P = 0.005) and current smoking (OR, 3.42; 95% CI, 1.47 to 8.62; P = 0.01).
      A relatively low incidence rate of DSSI (2.51%) was found in this study, and
      several significant risk factors were identified. Smoking cessation programmes
      should be implemented immediately after hospitalisation, especially for obesity
      and morbid obesity patients. Detailed and comprehensive preoperative assessment
      and a considerate operative plan should be guaranteed to reduce surgical
      duration.

PMID- 29193654
TI  - Technology Experience of Solid Organ Transplant Patients and Their Overall
      Willingness to Use Interactive Health Technology.
AB  - BACKGROUND: The use of interactive health technology (IHT) is a promising pathway
      to tackle self-management problems experienced by many chronically ill patients,
      including solid organ transplant (Tx) patients. Yet, to ensure that the IHT is
      accepted and used, a human-centered design process is needed, actively involving
      end users in all steps of the development process. A first critical,
      predevelopment step involves understanding end users' characteristics. This study
      therefore aims to (a) select an IHT platform to deliver a self-management support
      intervention most closely related to Tx patients' current use of information and
      communication technologies (ICTs), (b) understand Tx patients' overall
      willingness to use IHT for self-management support, and investigate associations
      with relevant technology acceptance variables, and (c) explore Tx patients' views
      on potential IHT features. DESIGN AND METHODS: We performed a cross-sectional,
      descriptive study between October and December 2013, enrolling a convenience
      sample of adult heart, lung, liver, and kidney Tx patients from the University
      Hospitals Leuven, Belgium. Broad inclusion criteria were applied to ensure a
      representative patient sample. We used a 35-item newly designed interview
      questionnaire to measure Tx patients' use of ICTs, their overall willingness to
      use IHT, and their views on potential IHT features, as well as relevant
      technology acceptance variables derived from the Unified Theory of Acceptance and
      Use of Technology and a literature review. Descriptive statistics were used as
      appropriate, and an ordinal logistic regression model was built to determine the
      association between Tx patients' overall willingness to use IHT, the selected
      technology acceptance variables, and patient characteristics. FINDINGS: Out of
      139 patients, 122 agreed to participate (32 heart, 30 lung, 30 liver, and 30
      kidney Tx patients; participation rate: 88%). Most patients were male (57.4%),
      married or living together (68%), and had a mean age of 55.9 +/- 13.4 years. Only
      27.9% of Tx patients possessed a smartphone, yet 72.1% owned at least one desktop
      or laptop PC with wireless Internet at home. On a 10-point numeric scale, asking
      patients whether they think IHT development is important to support them
      personally in their self-management, patients gave a median score of 7 (25th
      percentile 5 points; 75th percentile 10 points). Patients who were single or
      married or living together were more likely to give a higher rating than divorced
      or widowed patients; patients who completed only secondary education gave a
      higher rating than higher educated patients; and patients with prior ICT use gave
      a higher rating than patients without prior ICT use. Tx patients also had clear
      preferences regarding IHT features, such as automatic data transfer, as much as
      possible, visual aids (e.g., graphs) over text messages, and personally deciding
      when to access the IHT. CONCLUSIONS: By investigating Tx patients' possession and
      use of ICTs, we learned that computers and the Internet, and not smartphones, are
      the most suitable IHT platforms to deliver self-management interventions for our
      Tx patients. Moreover, Tx patients generally are open to using IHT, yet patient
      acceptance variables and their preferences for certain IHT features should be
      taken into account in the next steps of IHT development. Designers intending to
      develop or use existing IHTs should never overlook this critical first step in a
      human-centered design. CLINICAL RELEVANCE: Before considering using eHealth
      technology in clinical practice, professionals should always check whether
      patients are familiar with using information and communication technology, and
      whether they are willing to use technology for health-related purposes.

PMID- 29193655
TI  - Polygenic risk scores distinguish patients from non-affected adult relatives and
      from normal controls in schizophrenia and bipolar disorder multi-affected
      kindreds.
AB  - Recent studies have used results on SNP association with schizophrenia (SZ) and
      bipolar disorder (BD) to create polygenic risk scores (PRS) discriminating non
      familial unrelated patients from controls. Little is known about the role of PRS
      in densely affected multigenerational families. We tested PRS differences between
      affected SZ and BD family members from their non-affected adult relatives (NAARs)
      in Eastern Quebec Kindreds and from controls. We examined 1227 subjects: from 17
      SZ and BD kindreds, we studied 153 patients (57 SZ, 13 schizoaffective, and 83
      BD) and 180 NAARs, and 894 unrelated controls from the Eastern Quebec population.
      PRS were derived from published case-control association studies of SZ and BD. We
      also constructed a combined SZ and BD PRS by using SNPs from both SZ and BD PRS.
      SZ patients had higher SZ PRS than controls (p = 0.0039, R2  = 0.027) and BD
      patients had higher BD PRS than controls (p = 0.013, R2  = 0.027). Differences
      between affected subjects and NAARs and controls were significant with both SZ
      and BD PRS. Moreover, a combined SZ-BD PRS was also significantly associated with
      SZ and BD when compared to NAARs (p = 0.0019, R2  = 0.010) and controls (p =
      0.0025, R2  = 0.028), revealing a SZ-BD commonality effect in PRS at the
      diagnosis level. The SZ and the BD PRS, however, showed a degree of specificity
      regarding thought disorder symptoms. Overall, our report would confirm the
      usefulness of PRS in capturing the contribution of common genetic variants to the
      risk of SZ and BD in densely affected families.

PMID- 29193656
TI  - Peritoneal Dialysis Related Peritonitis by Sphingomonas Paucimobilis.

PMID- 29193657
TI  - Mechanical properties, corrosion, and biocompatibility of Mg-Zr-Sr-Dy alloys for
      biodegradable implant applications.
AB  - This study investigates the microstructure, mechanical properties, corrosion
      behavior, and biocompatibility of magnesium (Mg)-based Mg1Zr2SrxDy (x = 0, 1,
      1.63, 2.08 wt %) alloys for biodegradable implant applications. The corrosion
      behavior of the Mg-based alloys has been evaluated in simulated body fluid using
      an electrochemical technique and hydrogen evolution. The biocompatibility of the
      Mg-based alloys has been assessed using SaSO2 cells. Results indicate that the
      addition of Dy to Mg-Zr-Sr alloy showed a positive impact on the corrosion
      behavior and significantly decreased the degradation rates of the alloys. The
      degradation rate of Mg1Zr2Sr1.0Dy decreased from 17.61 to 12.50 mm year-1 of
      Mg1Zr2Sr2.08Dy based on the hydrogen evolution. The ultimate compressive strength
      decreased from 270.90 MPa for Mg1Zr2Sr1Dy to 236.71 MPa for Mg1Zr2Sr2.08Dy. An
      increase in the addition of Dy to the Mg-based alloys resulted in an increase in
      the volume fraction of the Mg2 Dy phase, which mitigated the galvanic effect
      between the Mg17 Sr2 phase and the Mg matrix, and led to an increase in the
      corrosion resistance of the base alloy. The biocompatibility of the Mg-based
      alloys was enhanced with decreasing corrosion rates. Mg1Zr2Sr2.08Dy exhibited the
      lowest corrosion rate and the highest biocompatibility compared with the other Mg
      based alloys. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 106B: 2425-2434, 2018.

PMID- 29193658
TI  - Downregulation of dual-specificity tyrosine-regulated kinase 2 promotes tumor
      cell proliferation and invasion by enhancing cyclin-dependent kinase 14
      expression in breast cancer.
AB  - Tumor progression is the main cause of death in patients with breast cancer.
      Accumulating evidence suggests that dual-specificity tyrosine-regulated kinase 2
      (DYRK2) functions as a tumor suppressor by regulating cell survival,
      differentiation, proliferation and apoptosis. However, little is known about the
      mechanisms of transcriptional regulation by DYRK2 in cancer progression,
      particularly with respect to cancer proliferation and invasion. Here, using a
      comprehensive expression profiling approach, we show that cyclin-dependent kinase
      14 (CDK14) is a target of DYRK2. We found that reduced DYRK2 expression increases
      CDK14 expression, which promotes cancer cell proliferation and invasion in vitro,
      in addition to tumorigenicity in vivo. CDK14 and DYRK2 expression inversely
      correlated in human breast cancer tissues. We further identified androgen
      receptor (AR) as a candidate of DYRK2-dependent transcription factors regulating
      CDK14. Taken together, our findings suggest a mechanism by which DYRK2 controls
      CDK14 expression to regulate tumor cell proliferation and invasion in breast
      cancer. Targeting of this pathway may be a promising therapeutic strategy for
      treating breast cancer.

PMID- 29193659
TI  - S2k Guidelines - Cutaneous Lymphomas Update 2016 - Part 1: Classification and
      Diagnosis (ICD10 C82 - C86).

PMID- 29193660
TI  - Preterm birth with placental evidence of malperfusion is associated with
      cardiovascular risk factors after pregnancy: a prospective cohort study.
AB  - OBJECTIVE: Preterm birth (PTB) is associated with excess maternal cardiovascular
      disease risk. We considered that women with PTB and placental evidence of
      maternal malperfusion would be particularly affected. DESIGN: Pregnancy cohort
      study. SETTING: Pittsburgh, PA, USA. POPULATION: Women with PTB (n = 115) and
      term births (n = 210) evaluated 4-12 years after pregnancy. METHODS:
      Cardiometabolic risk markers were compared in women with prior PTB versus term
      births; pre-eclampsia and growth restriction cases were excluded. Placental
      evidence of maternal vascular malperfusion (vasculopathy, infarct, advanced
      villous maturation, perivillous fibrin, intervillous fibrin deposition), acute
      infection/inflammation (chorioamnionitis, funisitis, deciduitus) and villitis of
      unknown aetiology (chronic inflammation) was used to classify PTBs. MAIN OUTCOME
      MEASURES: Carotid artery intima-media thickness (IMT), fasting lipids, blood
      pressure (BP) and inflammatory markers measured after delivery. RESULTS: Women
      with PTB and malperfusion lesions had higher total cholesterol (+13.5 mg/dl) and
      systolic BP (+4.0 mmHg) at follow up compared with women with term births,
      accounting for age, race, pre-pregnancy BMI, and smoking (P < 0.05). Women with
      PTB and malperfusion accompanied by inflammatory lesions had the most atherogenic
      profile after pregnancy (cholesterol +18.7, apolipoprotein B + 12.7 mg/dl; all P
      < 0.05), adjusted for pre-pregnancy features. Carotid IMT was higher in this
      group (+0.037 cm, P = 0.031) accounting for pre-pregnancy factors; differences
      were attenuated after adjusting for BP and atherogenic lipids at follow up
      (+0.027, P = 0.095). CONCLUSION: PTBs with placental malperfusion were associated
      with an excess maternal cardiometabolic risk burden in the decade after
      pregnancy. The placenta may offer insight into subtypes of PTB related to
      maternal cardiovascular disease. TWEETABLE ABSTRACT: Preterm births with
      placental malperfusion may mark women at higher cardiovascular disease risk.

PMID- 29193661
TI  - The C2H2 zinc-finger protein SlZF3 regulates AsA synthesis and salt tolerance by
      interacting with CSN5B.
AB  - Abiotic stresses are a major cause of crop loss. Ascorbic acid (AsA) promotes
      stress tolerance by scavenging reactive oxygen species (ROS), which accumulate
      when plants experience abiotic stress. Although the biosynthesis and metabolism
      of AsA are well established, the genes that regulate these pathways remain
      largely unexplored. Here, we report on a novel regulatory gene from tomato
      (Solanum lycopersicum) named SlZF3 that encodes a Cys2/His2-type zinc-finger
      protein with an EAR repression domain. The expression of SlZF3 was rapidly
      induced by NaCl treatments. The overexpression of SlZF3 significantly increased
      the levels of AsA in tomato and Arabidopsis. Consequently, the AsA-mediated ROS
      scavenging capacity of the SlZF3-overexpressing plants was increased, which
      enhanced the salt tolerance of these plants. Protein-protein interaction assays
      demonstrated that SlZF3 directly binds CSN5B, a key component of the COP9
      signalosome. This interaction inhibited the binding of CSN5B to VTC1, a GDP
      mannose pyrophosphorylase that contributes to AsA biosynthesis. We found that the
      EAR domain promoted the stability of SlZF3 but was not required for the
      interaction between SlZF3 and CSN5B. Our findings indicate that SlZF3
      simultaneously promotes the accumulation of AsA and enhances plant salt-stress
      tolerance.

PMID- 29193662
TI  - The beneficial effects of probiotic administration on wound healing and metabolic
      status in patients with diabetic foot ulcer: A randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: This study was conducted to evaluate the effects of probiotic
      supplementation on wound healing and metabolic status in subjects with diabetic
      foot ulcer (DFU). METHODS: This randomized, double-blind, placebo-controlled
      trial was conducted among 60 subjects (aged 40-85 years old) with grade 3
      diabetic foot ulcer. Individuals were randomly divided into 2 groups (30 subjects
      each group) to receive either probiotic or placebo daily for 12 weeks. RESULTS:
      After the 12-week intervention, compared with the placebo, probiotic
      supplementation led to significant reductions in ulcer length (-1.3 +/- 0.9 vs. 
      0.8 +/- 0.7 cm, P = .01), width (-1.1 +/- 0.7 vs. -0.7 +/- 0.7 cm, P = .02), and
      depth (-0.5 +/- 0.3 vs. -0.3 +/- 0.3 cm, P = .02). Furthermore, significant
      reductions in fasting plasma glucose (-29.6 +/- 30.3 vs. -5.8 +/- 39.8 mg/dL, P =
      .01), serum insulin concentrations (-4.3 +/- 7.9 vs. +0.4 +/- 8.5 MUIU/mL, P =
      .03), and haemoglobin A1c (-0.6 +/- 0.5 vs. -0.2 +/- 0.4%, P = .003) and a
      significant rise in the quantitative insulin sensitivity check index (+0.01 +/-
      0.01 vs. -0.01 +/- 0.02, P = .003) were seen following supplementation of
      probiotic compared with the placebo. Additionally, compared with the placebo,
      probiotic supplementation resulted in significant decreases in serum total
      cholesterol (-4.8 +/- 16.1 vs. +7.0 +/- 27.1 mg/dL, P = .04), high-sensitivity C
      reactive protein (-9.0 +/- 14.7 vs. -1.7 +/- 8.6 mg/L, P = .02), plasma
      malondialdehyde (-0.8 +/- 0.8 vs. -0.2 +/- 0.8 MUmol/L, P = .001), and
      significant increases in plasma nitric oxide (+6.2 +/- 8.2 vs. +0.8 +/- 8.0
      MUmol/L, P = .01) and total antioxidant capacity concentrations (+179.3 +/- 97.2
      vs. -85.1 +/- 203.4 mmol/L, P < .001). CONCLUSIONS: Overall, probiotic
      supplementation for 12 weeks among subjects with diabetic foot ulcer had
      beneficial effects on ulcer size, glycaemic control, total cholesterol, high
      sensitivity C-reactive protein, plasma nitric oxide, total antioxidant capacity,
      and malondialdehyde levels.

PMID- 29193663
TI  - Clinical and genetic characterization of AP4B1-associated SPG47.
AB  - The hereditary spastic paraplegias (HSPs) are a heterogeneous group of disorders
      characterized by degeneration of the corticospinal and spinocerebellar tracts
      leading to progressive spasticity. One subtype, spastic paraplegia type 47 (SPG47
      or HSP-AP4B1), is due to bi-allelic loss-of-function mutations in the AP4B1 gene.
      AP4B1 is a subunit of the adapter protein complex 4 (AP-4), a heterotetrameric
      protein complex that regulates the transport of membrane proteins. Since 2011, 11
      individuals from six families with AP4B1 mutations have been reported, nine of
      whom had homozygous mutations and were from consanguineous families. Here we
      report eight patients with AP4B1-associated SPG47, the majority born to non
      consanguineous parents and carrying compound heterozygous mutations. Core
      clinical features in this cohort and previously published patients include
      neonatal hypotonia that progresses to spasticity, early onset developmental delay
      with prominent motor delay and severely impaired or absent speech development,
      episodes of stereotypic laughter, seizures including frequent febrile seizures,
      thinning of the corpus callosum, and delayed myelination/white matter loss. Given
      that some of the features of AP-4 deficiency overlap with those of cerebral
      palsy, and the discovery of the disorder in non-consanguineous populations, we
      believe that AP-4 deficiency may be more common than previously appreciated.

PMID- 29193664
TI  - Genome-wide discovery of tissue-specific miRNAs in clusterbean (Cyamopsis
      tetragonoloba) indicates their association with galactomannan biosynthesis.
AB  - Owing to the presence of 80% soluble dietary fibre, high protein content and high
      value gum, clusterbean (Cyamopsis tetragonoloba) has recently emerged as an
      economically important legume. The developing clusterbean seeds accumulate 90%
      galactomannans in the endosperm and, therefore, can be used as a model crop to
      understand galactomannan biosynthesis and its regulation. miRNAs are tiny master
      regulators of their corresponding target genes, resulting in variations in the
      amounts of their metabolic end products. To understand the role of these
      regulators in galactomannan biosynthesis regulation, small RNA libraries were
      prepared and sequenced from five tissues of clusterbean genotype RGC-936, and
      miRanalyzer and DSAP programs were used to identify conserved miRNAs and novel
      small RNAs. A total of 187 known and 171 novel miRNAs were found to be
      differentially expressed, of which 10 miRNAs were validated. A complicated
      network topology and 35% sharing of the target mRNAs between known and novel
      miRNAs suggest random evolution of novel miRNAs. The gene ontology (GO)
      annotation of potential target genes revealed the genes coding for signalling and
      carbohydrate metabolism (50.10%), kinases and other enzymes (20.75%),
      transcription factors (10.20%), transporters (8.35%) and other targets (10.6%).
      Two novel unigenes were annotated as ManS (mannosyltransferase/mannan synthase)
      and UGE (UDP- D-glucose 4-epimerase) and validated as targets for three novel
      miRNAs, that is Ct-miR3130, Ct-miR3135 and Ct-miR3157. Our findings reveal that
      these novel miRNAs could play an important role in the regulation of the
      galactomannan pathway in C. tetragonoloba and possibly other galactomannan
      producing species.

PMID- 29193666
TI  - Shifts in air temperature and high-magnitude winter precipitation events in
      coastal North America: Implications for Environmental Assessment and Management.
AB  - This commentary examines recent shifts in air temperature data coinciding with
      high-magnitude precipitation events at climate stations spanning an elevational
      and longitudinal gradient on the south coast of British Columbia, Canada. Results
      presented show that high-magnitude winter precipitation events are occurring on
      British Columbia's south coast under progressively warmer conditions. In the
      future, proportionally more winter precipitation is anticipated to report as
      rainfall versus snow, and over time these changes will have a marked impact on
      the snowmelt-dominated hydrographs that characterize local watersheds. Robust
      preparedness strategies will be needed to balance competing interests such as the
      security of domestic water supplies, the permitting and operation of major
      projects (e.g., mines, hydrodevelopments), and the achievement of broader
      ecosystem health goals under these changing hydroclimatic conditions. Integr
      Environ Assess Manag 2018;14:185-188. (c) 2018 SETAC.

PMID- 29193665
TI  - Provitamin A biofortification of cassava enhances shelf life but reduces dry
      matter content of storage roots due to altered carbon partitioning into starch.
AB  - Storage roots of cassava (Manihot esculenta Crantz), a major subsistence crop of
      sub-Saharan Africa, are calorie rich but deficient in essential micronutrients,
      including provitamin A beta-carotene. In this study, beta-carotene concentrations
      in cassava storage roots were enhanced by co-expression of transgenes for deoxy-d
      xylulose-5-phosphate synthase (DXS) and bacterial phytoene synthase (crtB),
      mediated by the patatin-type 1 promoter. Storage roots harvested from field-grown
      plants accumulated carotenoids to <=50 MUg/g DW, 15- to 20-fold increases
      relative to roots from nontransgenic plants. Approximately 85%-90% of these
      carotenoids accumulated as all-trans-beta-carotene, the most nutritionally
      efficacious carotenoid. beta-Carotene-accumulating storage roots displayed
      delayed onset of postharvest physiological deterioration, a major constraint
      limiting utilization of cassava products. Large metabolite changes were detected
      in beta-carotene-enhanced storage roots. Most significantly, an inverse
      correlation was observed between beta-carotene and dry matter content, with
      reductions of 50%-60% of dry matter content in the highest carotenoid
      accumulating storage roots of different cultivars. Further analysis confirmed a
      concomitant reduction in starch content and increased levels of total fatty
      acids, triacylglycerols, soluble sugars and abscisic acid. Potato engineered to
      co-express DXS and crtB displayed a similar correlation between beta-carotene
      accumulation, reduced dry matter and starch content and elevated oil and soluble
      sugars in tubers. Transcriptome analyses revealed a reduced expression of genes
      involved in starch biosynthesis including ADP-glucose pyrophosphorylase genes in
      transgenic, carotene-accumulating cassava roots relative to nontransgenic roots.
      These findings highlight unintended metabolic consequences of provitamin A
      biofortification of starch-rich organs and point to strategies for redirecting
      metabolic flux to restore starch production.

PMID- 29193667
TI  - With adaptation, the WHO guidelines on calcium supplementation for prevention of
      pre-eclampsia are adopted by pregnant women.
AB  - The World Health Organization (WHO) recommends calcium supplementation for
      prevention of pre-eclampsia, but factors affecting adoption and acceptability of
      the recommendations among pregnant women have not been examined. We explored
      adoption of the WHO guidelines in Kenya, using the trials of improved practices.
      We recruited 38 pregnant women and assigned participants to three regimens
      representing potential trade-offs among daily dose, bioavailability, and
      acceptability. Participants were provided with supplements, requested to select
      preferred product type, counselled on how to take them, and interviewed 4 times
      over 6 weeks to assess their experiences. We tracked bottle opening with
      electronic monitors, as proxy for supplement consumption. We analysed interview
      transcripts thematically. All participants were willing to try the supplements.
      Average daily consumption ranged from 77 to 1,577 mg/d. Most participants (74%)
      chose the chewable product. Participants preferred its "sweet taste" and liked
      the ability to consume it without water. Women in the 2-dose regimen were least
      likely to switch; however, women assigned to the 3-dose regimen, or who switched
      to the 3-dose regimen, consumed the most calcium per day. Difficulties with the 4
      dose regimen included afternoon doses when women were likely to forget and having
      to wait hours after supper for last dose. Use of an illustrated calendar, keeping
      supplements in conspicuous locations and requesting support from relatives were
      strategies that supported adherence. Pregnant women are likely to adopt Ca
      supplementation, with appropriate programmatic adaptations. Careful attention to
      product attributes, regimen complexity, and strategies for reassuring and
      reminding women are needed to adapt the WHO guidelines.

PMID- 29193668
TI  - Longitudinal study of short-term corticosteroid use by working-age adults with
      diabetes mellitus: Risks and mitigating factors.
AB  - BACKGROUND: This study assessed the frequency of short-term oral corticosteroid
      use in adults with diabetes, examined the incidence of fractures, venous
      thromboembolism (VTE), and hospitalization for sepsis after corticosteroid use,
      and evaluated whether preventative medications mitigated adverse events. METHODS:
      A longitudinal study (2012-14) was conducted of 1 548 945 adults (aged 18-64
      years) who received healthcare coverage through a large national health insurer.
      Incidence rate ratios (IRR) were calculated using conditional Poisson regression.
      RESULTS: Short-term oral corticosteroids were used by 23.9%, 20.8%, and 20.9% of
      adults with type 2 diabetes, type 1 diabetes, and no diabetes, respectively,
      during the 3-year period (P < 0.001). Baseline risks of fracture, VTE, and sepsis
      were greater for individuals with than without diabetes (P < 0.001). The combined
      effect of having diabetes and using corticosteroids was greater than the sum of
      the individual effects (synergy indices of 1.17, 1.23, 1.30 for fracture, VTE,
      and sepsis, respectively). The IRR for VTE in the 5-30 days after corticosteroid
      use was 3.62 (95% confidence interval [CI] 2.41-5.45). Fractures increased in the
      5-30 days after corticosteroid use (IRR 2.06; 95% CI 1.52, 2.80), but concomitant
      use of ergocalciferol mitigated this risk (IRR 1.13; 95% CI 0.12, 11.07). The
      risk of hospitalization for sepsis was elevated with corticosteroid use (IRR
      3.79; 95% CI 2.05, 7.01), but was mitigated by the concomitant use of statins.
      CONCLUSIONS: Short-term oral corticosteroid use is common in adults with diabetes
      and is associated with an elevated, but low, risk of adverse events. The findings
      suggest that preventative medications may mitigate risk.

PMID- 29193669
TI  - Serial lipase for pancreatitis: not enough evidence.
AB  - BACKGROUND: Lipase is both a sensitive and specific marker for diagnosing
      pancreatitis. However, the benefit of serial lipase in both monitoring and
      defining prognosis remains undetermined. This systematic review was conducted to
      further evaluate this potential application. In addition, this review also looked
      into the benefits of serial lipase in the subgroup of traumatic pancreatitis.
      METHODS: PubMed, Cochrane Library and Google Scholar were systematically searched
      for related articles, between January 1995 and December 2015, according to
      Preferred Reporting Items for Systematic Reviews and Meta-analyses standards.
      Data was extracted and analysed by two authors. RESULTS: Seven studies were
      included in the final analysis: six retrospective and one prospective studies
      were identified. Five studies (all retrospective) concluded no benefits in serial
      lipase for prognostication, while two studies identified serial lipase as a
      beneficial prognostic factor for acute pancreatitis. Of the included studies,
      only two involved traumatic pancreatitis (both dedicated to the paediatric
      population). CONCLUSION: The evidence supporting or opposing serial lipase as a
      prognostic factor for pancreatitis is weak and consists mainly of retrospective
      analyses. The only prospective data identified suggested benefits to serial
      lipase in prognosis. Further prospective studies evaluating the prognostic value
      of serial lipase in the adult population with both traumatic and non-traumatic
      pancreatitis are required given the paucity of available evidence.

PMID- 29193670
TI  - Stable Low-Current Electrodeposition of alpha-MnO2 on Superaligned Electrospun
      Carbon Nanofibers for High-Performance Energy Storage.
AB  - Metal oxide/carbonaceous nanomaterials are promising candidates for energy
      storage applications. However, inhomogeneous mass and charge transfer across the
      electrode/electrolyte interface due to unstable metal oxide/carbonaceous
      nanomaterial synthesis limit their performance in supercapacitors. Here, it is
      shown that the above problems can be mitigated through stable low-current
      electrodeposition of MnO2 on superaligned electrospun carbon nanofibers (ECNFs).
      The key to this approach is coupling a self-designed four steel poles collector
      for aligned ECNFs and a constant low-current (40 uA) electrodeposition technique
      to form a uniform Na+ -induced alpha-MnO2 film which proceeds by a time-dependent
      growth mechanism involving cluster-"kebab" structures and ending with a compact,
      uniform MnO2 film for high-performance energy storage.

PMID- 29193671
TI  - Percutaneous transcatheter pulmonary valve replacement in children weighing less
      than 20 kg.
AB  - BACKGROUND: Since FDA approval of the Melody valve, transcatheter pulmonary valve
      replacement (TPVR) has been offered to an expanding population. Limited data
      exist regarding the safety and feasibility of TPVR in smaller patients. METHODS:
      All patients weighing <20 kg who underwent catheterization for percutaneous TPVR
      at four centers were reviewed. RESULTS: Of the 51 patients reviewed, 43 (84%) had
      successful valve implantation and 8 (16%) were found not to be candidates due to
      access veins too small (n = 3), coronary artery/aortic root compression (n = 3),
      and RVOT too large (n = 2). The 43 patients who underwent successful percutaneous
      TPVR had a median age and weight of 5.8 years (3.3-10) and 17.7 kg (13.5-19.8),
      and most had tetralogy of Fallot (TOF). TPVR was performed via femoral vein (FV)
      access in 24 patients and internal jugular vein (IJV) access in 19 patients.
      Median weight in patients with IJV implant was 1.1 kg lower than those who
      underwent transfemoral implant (17.0 vs. 18.1 kg, P = 0.05). There were four
      adverse events: one iliac vein injury, one contained MPA tear, and two patients
      with post-procedure femoral vein bleeding. All patients were alive at recent
      follow-up, a median of 2.0 years (0.1-6.0) after TPVR. There was excellent valve
      function with mean Doppler gradients of 3-20 mm Hg, and trivial or mild pulmonary
      regurgitation in all but one patient. There were no RVOT reinterventions and no
      cases of endocarditis. CONCLUSIONS: Percutaneous TPVR can be safely performed in
      patients <20 kg. The procedure frequently requires IJV access, and access
      site/bleeding complications may be more common in this cohort.

PMID- 29193672
TI  - Deforestation may increase soil carbon but it is unlikely to be continuous or
      unlimited.

PMID- 29193673
TI  - Ophthalmic features of cone-rod dystrophy caused by pathogenic variants in the
      ALMS1 gene.
AB  - PURPOSE: We aim to describe ophthalmic characteristics and systemic findings in a
      cohort of seven patients with cone-rod retinal dystrophy (CORD) caused by
      pathogenic variants in the ALMS1 gene. METHODS: Seven patients with Alstrom
      syndrome (ALMS) were included in the study. A comprehensive ophthalmological
      examination was performed, including best-corrected visual acuity (BCVA), a
      semiautomated kinetic visual field exam, colour vision testing, full-field
      electroretinography testing according to International Society for Clinical
      Electrophysiology of Vision (ISCEV) standards, spectral domain optical coherence
      tomography (SD-OCT) and fundus autofluorescence (FAF) imaging, and slit lamp and
      dilated fundus examination. DNA samples were analysed using Sanger sequencing or
      exome sequencing. RESULTS: In our cohort, the ocular phenotype presented with a
      wide variability in retinal function and disease severity. However, age of
      symptom onset (i.e. nystagmus and photophobia) was at 6-9 months in all patients.
      These symptoms mostly mislead to the diagnosis of congenital achromatopsia
      (ACHM), Leber congenital amaurosis (LCA), isolated CORD or Bardet-Biedl syndrome.
      The systemic manifestations in our cohort were highly variable. CONCLUSION: In
      summary, we can report that most of our ALMS patients primarily presented with
      nystagmus and severe photophobia since early childhood interestingly without
      night blindness in the absence of systemic symptoms. Only genetic testing
      analysing both nonsyndromic retinal disease (RD) genes and syndromic ciliopathy
      genes by comprehensive panel sequencing can result in the correct diagnosis,
      genetically and clinically, with important implication for the physical health of
      the individual.

PMID- 29193674
TI  - Potential Impact of Metabolic and Gut Microbial Response to Pregnancy and
      Lactation in Lean and Diet-Induced Obese Rats on Offspring Obesity Risk.
AB  - SCOPE: Maternal obesity programs metabolic dysfunction in offspring, increasing
      their susceptibility to obesity and metabolic diseases in later life. Moreover,
      pregnancy and lactation are associated with many metabolic adaptations, yet it is
      unclear how diet-induced maternal obesity may interrupt these processes. METHODS
      AND RESULTS: 1 H NMR serum metabolomics analysis was performed on samples
      collected pre-pregnancy and in pregnant and lactating lean and high fat/sucrose
      (HFS) diet-induced obese Sprague-Dawley rats to identify maternal metabolic
      pathways associated with developmental programming of offspring obesity. Gut
      microbial composition was assessed using qPCR. Offspring of HFS dams had nearly
      40% higher adiposity at weaning compared to offspring of lean dams. While
      pregnancy and lactation were associated with distinct maternal metabolic changes
      common to both lean and obese dams, we identified several metabolic differences,
      potentially implicating dysregulated one-carbon and mammary gland metabolism in
      the metabolic programming of obesity. Gut microbial composition was significantly
      altered with obesity, and both gestation and lactation were accompanied by
      changes in gut microbiota. CONCLUSION: Diet-induced maternal obesity and
      consumption of an obesogenic maternal diet results in differential metabolic and
      gut microbial adaptations to pregnancy and lactation; these maladaptations may be
      directly involved in maternal programming of offspring susceptibility to obesity.

PMID- 29193675
TI  - Gene expression in response to glyphosate treatment in fleabane (Conyza
      bonariensis) - glyphosate death response and candidate resistance genes.
AB  - BACKGROUND: This study takes a whole-transcriptome approach to assess gene
      expression changes in response to glyphosate treatment in glyphosate-resistant
      fleabane. We assessed gene expression changes in both susceptible and resistant
      lines so that the glyphosate death response could be quantified, and
      constitutively expressed candidate resistance genes identified. There are three
      copies of the glyphosate target site (5-enolpyruvylshikimate-3-phosphate; EPSPS)
      gene in Conyza and because Conyza bonariensis is allohexaploid, there is a
      baseline nine copies of the gene in any individual. RESULTS: Many genes were
      differentially expressed in response to glyphosate treatment. Known resistance
      mutations are present in EPSPS2 but they are present in a glyphosate-susceptible
      line as well as resistant lines and therefore not sufficient to confer
      resistance. EPSPS1 is expressed four times more than EPSPS2, further reducing the
      overall contribution of these mutations. CONCLUSION: We demonstrate that
      glyphosate resistance in C. bonariensis is not the result of EPSPS mutations or
      overexpression, but due to a non-target-site mechanism. A large number of genes
      are affected by glyphosate treatment. We present a list of candidate non-target
      site-resistance (NTSR) genes in fleabane for future studies into these
      mechanisms. (c) 2017 Society of Chemical Industry.

PMID- 29193676
TI  - Poly (amido amine) dendrimer and dental adhesive with calcium phosphate
      nanoparticles remineralized dentin in lactic acid.
AB  - Patients with dry mouth often have an acidic oral environment lacking saliva to
      provide calcium (Ca) and phosphate (P) ions. There has been no report on tooth
      remineralization in acidic pH4 and CaP ion-lacking solutions. The objective of
      this study was to develop a novel method of combining poly(amido amine) (PAMAM)
      with adhesive containing nanoparticles of amorphous calcium phosphate (NACP) for
      dentin remineralization in pH4 and CaP-lacking solution for the first time.
      Demineralized dentin was tested in four groups: (1) dentin control, (2) dentin
      with PAMAM, (3) dentin with NACP adhesive, (4) dentin with PAMAM + NACP adhesive.
      Dentin samples were examined by scanning electron microscopy (SEM), energy
      dispersive spectroscopy (EDS) and hardness testing. Increasing the NACP filler
      level in adhesive from 0 to 40 wt% did not negatively affect the dentin bond
      strength (p > 0.1). NACP adhesive released CaP ions and neutralized the acid.
      PAMAM alone failed to achieve dentin remineralization in lactic acid. NACP alone
      induced slight dentin remineralization in lactic acid (p > 0.1). In contrast, the
      novel PAMAM + NACP group in the pH4 and CaP-lacking solution completely
      remineralized the predemineralized dentin, increasing its hardness which
      approached that of healthy dentin (p > 0.1). In conclusion, dentin
      remineralization via PAMAM + NACP adhesive in pH4 and CaP-lacking acid was
      achieved for the first time, when conventional remineralization methods such as
      PAMAM or NACP did not work. The novel PAMAM + NACP method is promising to
      increase the longevity of the composite-tooth bond, inhibit caries, remineralize
      lesions and protect tooth structures, even for patients with dry mouth and an
      acidic oral environment. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part
      B: Appl Biomater, 106B: 2414-2424, 2018.

PMID- 29193677
TI  - Gallic Acid Improves Health-Associated Biochemical Parameters and Prevents
      Oxidative Damage of DNA in Type 2 Diabetes Patients: Results of a Placebo
      Controlled Pilot Study.
AB  - SCOPE: Oxidative imbalance plays a key role in cancer induction and
      cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM).
      The aim of this study is to find out if gallic acid (GA) prevents oxidative
      stress in diabetic patients. Therefore, we investigate its impact on oxidation of
      DNA bases and on other health-related macromolecules. METHODS AND RESULTS: We
      perform an intervention study (n = 19) with GA and monitored alterations of the
      DNA stability in single cell gel electrophoresis (SCGE) assays in lymphocytes.
      Furthermore, a panel of health-related biomarkers is measured before and after
      consumption of GA (15 mg p-1  d-1 ) for 7 d. Significant reduction of oxidized
      purines (by 31%, p < 0.001, effect size 0.404) and pyrimidines (by 2%, p < 0.022,
      effect size 0.089) is observed in SCGE assays. Furthermore, the plasma
      concentrations of oxidized-LDL and C-reactive protein are reduced after the
      intervention by 24% (p = 0.014, effect size 0.384) and 39% (p < 0.001, effect
      size 0.686), respectively. No alterations of other biomarkers are found.
      CONCLUSIONS: A small amount of GA (in the range of daily consumption in Central
      Europe) prevents oxidative DNA damage and reduces markers which reflect
      inflammation and increased risks of cancer and CVD.

PMID- 29193678
TI  - Total Syntheses of Daphenylline, Daphnipaxianine A, and Himalenine D.
AB  - We report the total syntheses of daphenylline (1), daphnipaxianine A (5), and
      himalenine D (6), three Daphniphyllum alkaloids from the calyciphylline A
      subfamily. A pentacyclic triketone was prepared by using atom-transfer radical
      cyclization and the Lu [3+2] cycloaddition as key steps. Inspired by the proposed
      biosynthetic relationship between 1 and another calyciphylline A type alkaloid,
      we developed a ring-expansion/aromatization/aldol cascade to construct the
      tetrasubstituted benzene moiety of 1. The versatile triketone intermediate was
      also elaborated into 5 and 6 through a C=C bond migration/aldol cyclization
      approach.

PMID- 29193679
TI  - Increased Levels of 27-Hydroxycholesterol Induced by Dietary Cholesterol in Brain
      Contribute to Learning and Memory Impairment in Rats.
AB  - SCOPE: Dietary cholesterol has been shown to play a role in the development of
      Alzheimer's disease (AD). It is proposed that oxysterol especially 27
      hydroxycholesterol (27-OHC) may play a potential role in beta-amyloid peptides
      (Abeta) production and accumulation during AD progression. METHODS AND RESULTS:
      To investigate the mechanisms of dietary cholesterol and 27-OHC on learning and
      memory impairment, male Sprague-Dawley rats are fed with cholesterol diet with or
      without 27-OHC synthetase inhibitor (anastrozole) injection. The levels of
      cholesterol, 27-OHC, 24-hydroxycholesterol (24S-OHC), 7alpha-hydroxycholesterol,
      and 7beta-hydroxycholesterol in plasma are determined; apolipoprotein A (ApoA),
      apolipoprotein B (ApoB), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) in
      plasma or brain; CYP27A1 and CYP7A1 in liver and CYP46A1 and CYP7B1 in brain;
      cathepsin B, cathepsin D, and acid phosphatase in lysosome; and Abeta1-40 and
      Abeta1-42 in brain. Results show increased levels of 27-OHC (p < 0.01), LDL-C (p
      < 0.01), and ApoB (p < 0.01), and decreased level of HDL-C (p < 0.05) in plasma,
      upregulated CYP27A1 (p < 0.01) and CYP7A1 (p < 0.01) expression in liver, altered
      lysosomal function, and increased level of Abeta in brain (p < 0.05).
      CONCLUSIONS: This study indicates that the mechanisms of dietary cholesterol on
      learning and memory impairment may be involved in cholesterol metabolism and
      lysosome function with the increase of plasma 27-OHC, thus resulting in Abeta
      formation and accumulation.

PMID- 29193680
TI  - Larvicidal and residual activity of imidazolium salts against Aedes aegypti
      (Diptera: Culicidae).
AB  - BACKGROUND: Aedes aegypti is an important mosquito species that can transmit
      several arboviruses such as dengue fever, yellow fever, chikungunya and zika.
      Because these mosquitoes are becoming resistant to most chemical insecticides
      used around the world, studies with new larvicides should be prioritized. Based
      on the known biological profile of imidazolium salts (IS), the objective of this
      study was to evaluate the potential of six IS as larvicides against Ae. aegypti,
      as tested against Ae. aegypti larvae. Larval mortality was measured after 24 and
      48 h, and residual larvicidal activity was also evaluated. RESULTS: Promising
      results were obtained with aqueous solutions of two IS: 1-n-octadecyl-3
      methylimidazolium chloride (C18 MImCl) and 1-n-hexadecyl-3-methylimidazolium
      methanesulfonate (C16 MImMeS), showing up to 90% larval mortality after 48 h
      exposure. C18 MImCl was more effective than C16 mIMeS, causing mortality until
      day 15 after exposure. An application of C18 MImCl left to dry under ambient
      conditions for at least 2 months and then dissolved in water showed a more
      pronounced residual effect (36 days with 95% mortality and 80% mortality up to 78
      days). CONCLUSION: This is the first study to show the potential of IS in the
      control of Ae. aegypti. Further studies are needed to understand the mode of
      action of these compounds in the biological development of this mosquito species.
      (c) 2017 Society of Chemical Industry.

PMID- 29193682
TI  - Stretchable and Energy-Efficient Heating Carbon Nanotube Fiber by Designing a
      Hierarchically Helical Structure.
AB  - Inspired by the hierarchically helical structure of classical thermal insulation
      material-wool, a stretchable heating carbon nanotube (CNT) fiber is created with
      excellent mechanical and heating properties. It can be stretched by up to 150%
      with high stability and reversibility, and a good thermal insulation is achieved
      from a large amount of formed hierarchically helical voids inside. Impressively,
      it exhibits ultrafast thermal response over 1000  degrees C s-1 , low operation
      voltage of several volts, and high heating stability over 5000 cycles. These
      hierarchically helical CNT fibers, for the first time, are demonstrated as
      monofilaments to produce soft and lightweight textiles at a large scale with high
      heating performances.

PMID- 29193681
TI  - Angiogenic factors: potential to change clinical practice in pre-eclampsia?
AB  - : Pre-eclampsia is a complex disease with significant maternal and fetal
      morbidity and mortality. Its syndromic nature makes diagnosis and management
      difficult. The field is rapidly evolving with the definition of pre-eclampsia
      being challenged by some organisations, with proteinuria no longer being
      essential in the presence of other features. In the last decade, angiogenic
      factors, in particular soluble fms-like tyrosine kinase 1 (sFlt-1), have emerged
      as important molecules in the pathogenesis of pre-eclampsia. Here we review the
      most recent evidence regarding the potential of these factors as biomarkers and
      therapeutic targets for pre-eclampsia. TWEETABLE ABSTRACT: A review of angiogenic
      factors, sFlt-1 and PlGF, in the diagnosis, prediction and management of pre
      eclampsia.

PMID- 29193683
TI  - Prognostic value of urinary 11-dehydro-thromboxane B2 for mortality: A cohort
      study of stable coronary artery disease patients treated with aspirin.
AB  - AIM: There is a variable cardiovascular risk reduction attributable to aspirin
      because of individual differences in the suppression of thromboxane A2 and its
      downstream metabolite 11-dehydro-thromboxane B2 (11dhTxB2 ). The aim of this
      study is to evaluate the optimal cut point of urinary 11dhTxB2 for the risk of
      mortality in aspirin-treated coronary artery disease (CAD) patients. METHODS AND
      RESULTS: This was a prospective cohort study including stable CAD patients who
      visited the Baylor Heart and Vascular Hospital in Dallas or the Texas Heart
      Hospital Baylor Plano, TX between 2010 and 2013. The outcome of all-cause
      mortality was ascertained from chart review and automated sources. The 449
      patients included in this analysis had a mean age of 66.1 +/- 10.1 years. 67
      (14.9%) patients died within 5 years; 56 (87.5%) of the 64 patients with known
      cause of death suffered a cardiovascular related mortality. Baseline ln(urinary
      11dhTxB2 /creatinine) ranged between 5.8 and 11.1 (median = 7.2) with the higher
      concentrations among those who died (median: 7.6) than those who survived (median
      = 7.2, P < 0.001). Using baseline ln(11dhTxB2 ) to predict all-cause mortality,
      the area under the curve was 0.70 (95% CI: 0.64-0.76). The optimal cut point was
      found to be ln(7.38) = 1597.8 pg/mg, which had the following decision statistics:
      sensitivity = 0.67, specificity = 0.62, positive predictive value = 0.24,
      negative predictive value = 0.92, and accuracy = 0.63. CONCLUSION: Our data
      indicate the optimal cut point for urine 11dhTxB2 is 1597.8 (pg/mg) for the risk
      prediction of mortality over five years in stable patients with CAD patients
      treated with aspirin.

PMID- 29193685
TI  - A Scandium-Stabilized Diisophosphaethynolate Ligand: [OCPPCO]4.
AB  - The first example of the OCPPCO ligand, diisophosphaethynolate, is reported via
      reductive coupling of a Sc-OCP precursor. Upon reduction with KC8 , isolation of
      the dinuclear complex, namely [K(OEt2 )]2 [(nacnac)Sc(OAr)]2 (OCPPCO), is
      observed, leading to a unique motif [OCPPCO]4- , stabilized by two scandium
      centers. Detailed NMR spectra of all complexes as well as IR and single crystal X
      ray studies were obtained to fully elucidate the nature of these complexes in
      solution as well as in the solid state. Theory is combined to probe the
      electronic structure and orbitals responsible for the bonding interactions in the
      Sc-OCPPCO-Sc skeleton but also to compare to the linear mode observed in the
      precursor.

PMID- 29193686
TI  - Genetic linkage studies for the non-geneticist.

PMID- 29193684
TI  - Identification of a novel compound targeting the nuclear export of influenza A
      virus nucleoprotein.
AB  - Although antiviral drugs are available for the treatment of influenza infection,
      it is an urgent requirement to develop new antiviral drugs regarding the
      emergence of drug-resistant viruses. The nucleoprotein (NP) is conserved among
      all influenza A viruses (IAVs) and has no cellular equivalent. Therefore, NP is
      an ideal target for the development of new IAV inhibitors. In this study, we
      identified a novel anti-influenza compound, ZBMD-1, from a library of 20,000
      compounds using cell-based influenza A infection assays. We found that ZBMD-1
      inhibited the replication of H1N1 and H3N2 influenza A virus strains in vitro,
      with an IC50 ranging from 0.41-1.14 MUM. Furthermore, ZBMD-1 inhibited the
      polymerase activity and specifically impaired the nuclear export of NP. Further
      investigation indicated that ZBMD-1 binds to the nuclear export signal 3 (NES3)
      domain and the dimer interface of the NP pocket. ZBMD-1 also protected mice that
      were challenged with lethal doses of A/PR/8/1934 (H1N1) virus, effectively
      relieving lung histopathology changes, as well as strongly inhibiting the
      expression of pro-inflammatory cytokines/chemokines, without inducing toxicity
      effects in mice. These results suggest that ZBMD-1 is a promising anti-influenza
      compound which can be further investigated as a useful strategy against IAVs in
      the future.

PMID- 29193687
TI  - In vitro and in vivo biological characterization of poly(lactic acid) fiber
      scaffolds synthesized by air jet spinning.
AB  - Poly(lactic acid) (PLA) is one of the most promising renewable and biodegradable
      polymers for mimic extracellular matrix for tissue engineering applications. In
      this work, PLA spun membrane scaffold were successfully prepared by air jet
      spinning technology. Morphology, mechanical properties, in vitro
      biocompatibility, and in vitro and in vivo degradation of PLA fibrous scaffold
      were characterized by X-ray diffraction, Fourier Transform Infrared, and scanning
      electron microscope (SEM). Morphological results assessed by SEM analyses
      indicated that PLA scaffolds possessed an average fiber diameter of approximately
      0.558 +/- 0.141 um for 7% w/v of PLA and approximately 0.647 +/- 0.137 um for 10%
      w/v. Interestingly, our results showed that the nanofiber size of PLA scaffold
      allow structural stability after 100 days of in vitro degradation in Ringer
      solution where the average fiber diameter were of approximately 0.633 +/- 0.147
      um for 7% w/v and approximately 0.645 +/- 0.140 um for 10% w/v of PLA. Mechanical
      properties of PLA fibers scaffold after in vitro degradation showed decrease in
      terms of flexibility elongation, and less energy was needed to achieve maximal
      elastic deformation. The fiber size exerts an influence on the biological
      response of human Bone Marrow Mesenchymal Stromal Cells as confirmed by MTT assay
      after 9 days of cell culture and the in vivo degradation assay of 7% w/v and 10%
      w/v of PLA scaffold, did not demonstrate evidence of toxicity with a mild
      inflammatory respond. In conclusion, airbrushing technology promises to be a
      viable and attractive alternative technique for producing a biocompatible PLA
      nanofiber scaffold that could be considered for tissue engineering regeneration.
      (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B:
      2435-2446, 2018.

PMID- 29193688
TI  - Value of ablation therapy in the treatment of lung metastases.
AB  - Tumor metastases are the basic biological characteristics of malignant tumors,
      and the lungs are the second most prominent metastatic organs in which these
      develop after the liver. Currently, with the rapid development of ablation
      technology, ablation therapy as a local treatment is playing an increasingly
      important role in the treatment of lung metastases. Whether alone or in
      combination with other treatments, ablation therapy has achieved good therapeutic
      effects for the treatment of partial lung metastases. This article briefly
      summarizes the results of current and previous ablation treatments for lung
      metastases, and focuses on the value of ablation therapy for different kinds of
      lung metastases.

PMID- 29193690
TI  - Influenza-associated mortality in Yancheng, China, 2011-15.
AB  - INTRODUCTION: The Yangtze river delta in eastern China, centered on Shanghai, is
      one of the most populated regions of the world with more than 100 million
      residents. We examined the impact of influenza on excess mortality in Yancheng, a
      prefecture-level city with 8.2 million population located 250 km north of
      Shanghai, during 2011-2015. METHODS: We obtained individual data on deaths by
      date, age, sex, and cause in Yancheng from the Chinese Centers for Disease
      Control and Prevention, and used these to derive weekly rates of mortality from
      respiratory causes, respiratory and cardiovascular causes combined, and all
      causes. We used data on influenza-like illnesses and laboratory detections of
      influenza to construct a proxy measure of the weekly incidence of influenza virus
      infections in the community. We used regression models to estimate the
      association of influenza activity with mortality and excess mortality by age,
      cause, and influenza type/subtype. RESULTS: We estimated that an annual average
      of 4.59 (95% confidence interval: 3.94, 7.41) excess respiratory deaths per 100
      000 persons were associated with influenza, which was 4.6% of all respiratory
      deaths in the years studied. Almost all influenza-associated excess deaths
      occurred in persons >=65 years. Influenza A(H3N2) had the greatest impact on
      mortality and was associated with around 50% of the influenza-associated
      respiratory deaths in the 5 years studied. CONCLUSIONS: Influenza has a
      substantial impact on respiratory mortality in Yancheng, mainly in older adults.
      Influenza vaccination has the potential to reduce disease burden, and cost
      effectiveness analysis could be used to compare policy options.

PMID- 29193691
TI  - Purple Potato Extract Promotes Intestinal Epithelial Differentiation and Barrier
      Function by Activating AMP-Activated Protein Kinase.
AB  - SCOPE: Perturbation of gut epithelial barrier function induces inflammation and
      other health problems that originate from the gut. Purple potato contains a high
      content of beneficial polyphenolic compounds. The objective of this study is to
      evaluate the effect of purple potato extract (PPE) on intestinal differentiation
      and barrier function, and explore its underlying mechanism using Caco-2 cells and
      ex vivo cultured gut tissues. METHODS AND RESULTS: PPE increases transepithelial
      electrical resistance and decreases FITC-dextran paracellular flux in Caco-2
      cells, which are associated with strengthened intestinal epithelial
      differentiation in both Caco-2 cells and ex vivo guts. Furthermore, PPE treatment
      enhances AMP-activated protein kinase (AMPK) activity, concomitant with the
      increased expression of CDX2, a key transcriptional factor regulating intestinal
      epithelial differentiation. Knocking out AMPK using CRISPR/Cas9 system abolishes
      the positive effects of PPE on intestinal epithelial differentiation and barrier
      function, in junction with the reduced expression of CDX2. CONCLUSION: PPE
      improves gut epithelial differentiation and barrier function via activating AMPK,
      indicating that PPE, as well as associated purple potato consumption, could be
      used as a supportive dietary therapeutic strategy for improving gut epithelial
      health.

PMID- 29193689
TI  - Negative regulators of platelet activation and adhesion.
AB  - Platelets are small anucleated cells that constantly patrol the cardiovascular
      system to preserve its integrity and prevent excessive blood loss where the
      vessel lining is breached. Their key challenge is to form a hemostatic plug under
      conditions of high shear forces. To do so, platelets have evolved a molecular
      machinery that enables them to sense trace amounts of signals at the site of
      damage and to rapidly shift from a non-adhesive to a pro-adhesive state. However,
      this highly efficient molecular machinery can also lead to unintended platelet
      activation and cause clinical complications such as thrombocytopenia and
      thrombosis. Thus, several checkpoints are in place to tightly control platelet
      activation and adhesiveness in space and time. In this review, we will discuss
      select negative regulators of platelet activation, which are critical to maintain
      patrolling platelets in a quiescent, non-adhesive state and/or to limit platelet
      adhesion to sites of injury.

PMID- 29193692
TI  - Impact of African traditional worldviews on climate change adaptation.
AB  - Recent studies show cultural worldviews are a key determinant of environmental
      risk perceptions; thus, they could influence climate change adaptation
      strategies. African traditional worldviews encourage harmony between humans and
      the environment through a complex metaphysical belief system transmitted through
      folklore, taboos, and traditional knowledge. However, African traditional
      worldviews hold a belief in traditional gods that was shown to have a low
      connectedness to nature and a low willingness to change. In Makueni District,
      Kenya, 45% of agropastoralists surveyed believed drought was god's plan and could
      not be changed. In contrast, traditional knowledge, which is shaped by African
      traditional worldviews, is often used to frame adaptive strategies such as
      migration, changing modes of production, and planting different crop varieties.
      Furthermore, traditional knowledge has been used as a complement to science in
      areas where meteorological data was unavailable. However, the role of African
      traditional worldviews on climate change adaption remains understudied. Hence,
      there is a need to systematically establish the influence of African traditional
      worldviews on climate change risk perception, development of adaptive strategies,
      and policy formulation and implementation. In this commentary, we discuss the
      potential impacts of African traditional worldviews on climate change adaptation.
      Integr Environ Assess Manag 2018;14:189-193. (c) 2018 SETAC.

PMID- 29193694
TI  - Association between diabetes and mortality in elderly patients admitted for a
      first episode of acute heart failure.
AB  - AIM: To examine whether the presence of a prior diagnosis of diabetes mellitus
      (DM) influences mortality risk in elderly patients experiencing a first episode
      of heart failure (HF) hospitalization. METHODS: A total of 677 consecutive
      patients aged >=75 years admitted for a first episode of acute decompensated
      heart failure were evaluated according to the presence or not of DM, and in
      hospital and 1-year mortality rates were evaluated. RESULTS: A total of 240
      patients (35.4%) had a diagnosis of DM. Overall, 42 patients (6.2%) died during
      admission; and 205 patients (30.3%) died after 1 year; however, no differences
      were observed in mortality rates between both groups. Cox univariate analysis did
      not identify prior DM diagnosis as a risk factor for 1-year mortality (HR 0.767,
      P < 0.082). Multivariate analysis identified older age (HR 1.101, P < 0.0001),
      lower preadmission Barthel Index (HR 0.987, P = 0.002), higher heart rate (HR
      1.013, P = 0.02), higher admission serum potassium (HR 1.471, P = 0.016) and non
      prescription of angiotensin-converting enzyme inhibitors or angiotensin II
      receptor antagonists (HR 1.597, P = 0.018) as independent risk factors for 1-year
      mortality. CONCLUSIONS: More than one-third of elderly patients experiencing a
      first admission because of acute heart failure decompensation had a prior
      diagnosis of DM. However, DM did not seem to be associated to a significant 1
      year mortality risk. Geriatr Gerontol Int 2018; 18: 554-560.

PMID- 29193695
TI  - Climate conditions, and changes, affect microalgae communities... should we
      worry?
AB  - Microalgae play a pivotal role in the regulation of Earth's climate and its
      cycles, but are also affected by climate change, mainly by changes in
      temperature, light, ocean acidification, water stratification, and precipitation
      induced nutrient inputs. The changes and impacts on microalgae communities are
      difficult to study, predict, and manage, but there is no doubt that there will be
      changes. These changes will have impacts beyond microalgae communities, and many
      of them will be negative. Some actions are currently ongoing for the mitigation
      of some of the negative impacts, such as harmful algal blooms and water quality,
      but global efforts for reducing CO2 emissions, temperature rises, and ocean
      acidification are paramount for reducing the impact of climate change on
      microalgae communities, and eventually, on human well-being. Integr Environ
      Assess Manag 2018;14:181-184. (c) 2018 SETAC.

PMID- 29193696
TI  - A wake-up call to quiescent cancer cells - potential use of DYRK1B inhibitors in
      cancer therapy.
AB  - Nondividing cancer cells are relatively resistant to chemotherapeutic drugs and
      environmental stress factors. Promoting cell cycle re-entry of quiescent cancer
      cells is a potential strategy to enhance the cytotoxicity of agents that target
      cycling cells. It is therefore important to elucidate the mechanisms by which
      these cells are maintained in the quiescent state. The protein kinase dual
      specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) is
      overexpressed in a subset of cancers and maintains cellular quiescence by
      counteracting G0 /G1 -S phase transition. Specifically, DYRK1B controls the S
      phase checkpoint by stabilizing the cyclin-dependent kinase (CDK) inhibitor
      p27Kip1 and inducing the degradation of cyclin D. DYRK1B also stabilizes the
      DREAM complex that represses cell cycle gene expression in G0 arrested cells. In
      addition, DYRK1B enhances cell survival by upregulating antioxidant gene
      expression and reducing intracellular levels of reactive oxygen species (ROS).
      Substantial evidence indicates that depletion or inhibition of DYRK1B drives cell
      cycle re-entry and enhances apoptosis of those quiescent cancer cells with high
      expression of DYRK1B. Furthermore, small molecule DYRK1B inhibitors sensitize
      cells to the cytotoxic effects of anticancer drugs that target proliferating
      cells. These encouraging findings justify continued efforts to investigate the
      use of DYRK1B inhibitors to disrupt the quiescent state and overturn
      chemoresistance of noncycling cancer cells.

PMID- 29193697
TI  - Response to comments on: Sarcopenia is a risk factor for falling in independently
      living Japanese older adults: A 2-year prospective cohort study of the GAINA
      study.

PMID- 29193698
TI  - Comments on "Relationship between cardiac autonomic function and cognitive
      function in Alzheimer's disease".

PMID- 29193699
TI  - Comment on: Sarcopenia is a risk factor for falling in independently-living
      Japanese older adults: A 2-year prospective cohort study of the GAINA study.

PMID- 29193700
TI  - Authors' reply to the letter by Esra et al.

PMID- 29193701
TI  - Perceived Infection Prevention Climate and Its Predictors Among Nurses in Saudi
      Arabia.
AB  - PURPOSE: This study investigated the staff nurses' perception of the infection
      prevention climate and its predictors in two hospitals. DESIGN: This is a cross
      sectional study employing a convenience sample of 224 staff nurses at two general
      hospitals in Riyadh province. METHODS: The study utilized a two-part
      questionnaire that captures respondents' characteristics and the validated tool
      on Leading a Culture of Quality for Infection Prevention (LCQ-IP). Both
      descriptive and inferential statistics were utilized accordingly. RESULTS: The
      prioritization of quality received the highest mean score among the four factors
      of the scale (mean = 3.89, SD = 0.65), followed by supportive work environment
      (mean = 3.88, SD = 0.68), psychological safety (mean = 3.85, SD = 0.65), and
      improvement orientation (mean = 3.84, SD = 0.64). Nationality, clinical
      experience, and attendance to seminars or training were identified as significant
      predictors. CONCLUSIONS: The respondents perceived the infection prevention
      climate of the two general hospitals positively. This study strengthens the idea
      that organizational context influences negatively or positively the programs on
      infection prevention being implemented in the hospitals. CLINICAL RELEVANCE: The
      result may facilitate nursing and hospital management to reflect, examine, and
      review their organizational climate, the impact of infection prevention
      initiatives and patient safety strategies, and the reason to amend related
      policies or improve procedures, including the promotion of a healthy work
      environment.

PMID- 29193702
TI  - Role of anterior segment optical coherence tomography in angle-closure disease: a
      review.
AB  - This article aims to review the published literature pertaining to the use of
      anterior segment optical coherence tomography (AS-OCT) in the evaluation of angle
      closure disease. Searches on the available published literature were last
      conducted on 15 June 2017. Rated as Level I evidence, we found that AS-OCT has
      shown good sensitivity and moderate diagnostic accuracy to detect narrow angles
      when compared with gonioscopy. AS-OCT quantitative and qualitative parameters
      demonstrated strong association with the presence of gonioscopically closed
      angles. This technology provides an objective non-contact method of assessing the
      angle that is well tolerated by the patient and correlates well with the
      information provided by gonioscopy.

PMID- 29193703
TI  - Inflammation and thrombosis: roles of neutrophils, platelets and endothelial
      cells and their interactions in thrombus formation during sepsis.
AB  - The inflammatory response and the activation of coagulation are two important
      responses in a host's defense against infection. These mechanisms do not work
      independently, but cooperate in a complex and synchronous manner. Recent research
      has also shed light on the critical role of thrombus formation, which prevents
      the dissemination of microorganisms. The cellular components of blood vessels,
      i.e. leukocytes, platelets, erythrocytes, and vascular endothelial cells, play
      significant roles in the development of thrombi in combination with activation of
      the coagulation system. In addition to the cellular components, alarmins such as
      histones and high-mobility group box 1, microparticles and secreted granule
      proteins are all important for clot formation. In this summary, we review the
      pathophysiology of sepsis-induced coagulopathy and the role of cellular
      components and critical factors released from damaged cells. In addition, we
      review important therapeutic approaches that have been developed, are under
      investigation and are currently available in certain countries, including
      antithrombin, recombinant thrombomodulin, anti-Toll-like receptor 4 therapy, anti
      damage associated molecular pattern therapy, and hemoadsorption with a polymyxin
      B-immobilized fiber column.

PMID- 29193705
TI  - Orthopaedic medical tourism.

PMID- 29193704
TI  - The calcium-dependent kinase OsCPK24 functions in cold stress responses in rice.
AB  - Calcium-dependent protein kinases (CPKs) are serine/threonine protein kinases
      that function in plant stress responses. Although CPKs are recognized as key
      messengers in signal transduction, the specific roles of CPKs and the molecular
      mechanisms underlying their activity remain largely unknown. Here, we
      characterized the function of OsCPK24, a cytosol-localized calcium-dependent
      protein kinase in rice. OsCPK24 was universally and highly expressed in rice
      plants and was induced by cold treatment. Whereas OsCPK24 knockdown plants
      exhibited increased sensitivity to cold compared to wild type (WT), OsCPK24
      overexpressing plants exhibited increased cold tolerance. Plants overexpressing
      OsCPK24 exhibited increased accumulation of proline (an osmoprotectant) and
      glutathione (an antioxidant) and maintained a higher GSH/GSSG (reduced
      glutathione to oxidized glutathione) ratio during cold stress compared to WT. In
      addition to these effects in response to cold stress, we observed the kinase
      activity of OsCPK24 varied under different calcium concentrations. Further,
      OsCPK24 phosphorylated OsGrx10, a glutathione-dependent thioltransferase, at
      rates modulated by changes in calcium concentration. Together, our results
      support the hypothesis that OsCPK24 functions as a positive regulator of cold
      stress tolerance in rice, a process mediated by calcium signaling and involving
      phosphorylation and the inhibition of OsGrx10 to sustain higher glutathione
      levels.

PMID- 29193707
TI  - Akathisia-A psychopharmacologic treatment "menu".

PMID- 29193708
TI  - Teachers of Psychiatry Meeting in Chengdu.

PMID- 29193709
TI  - Annular atrophic lichen planus as a psychiatric problem.

PMID- 29193710
TI  - Effectiveness of the repeated administration of scopolamine ointment on clozapine
      induced hypersalivation in patients with treatment-resistant schizophrenia: A
      preliminary study.
AB  - INTRODUCTION: This study investigated the efficacy of scopolamine (an
      anticholinergic agent) ointment against clozapine-induced hypersalivation.
      METHODS: The patients enrolled in this study consisted of 10 clozapine-treated
      schizophrenia patients and 10 healthy adult men. A prospective, randomized,
      double-blind, crossover, placebo-controlled clinical trial was designed. RESULTS:
      A total of 10 patients and 10 healthy adult men completed the study. No
      significant reduction in the saliva production of the clozapine-treated patients
      was observed; however, that of the healthy adult men decreased significantly.
      DISCUSSION: Scopolamine ointment was not effective against clozapine-induced
      hypersalivation. A further study is necessary for confirming its effect.

PMID- 29193711
TI  - Early improvement predicts 8-week treatment outcome in patients with generalized
      anxiety disorder treated with escitalopram or venlafaxine.
AB  - INTRODUCTION: To investigate whether early improvement can predict 8-week
      treatment outcome in generalized anxiety disorder (GAD) patients. METHODS: For 8
      weeks, 226 GAD patients were randomly treated with escitalopram or venlafaxine.
      Early improvement was defined as a ?20% reduction from baseline in Hamilton
      anxiety rating scale at week 1 or 2. The positive and negative predictive values
      were calculated. RESULTS: The positive and negative predictive values of early
      improvement in escitalopram or venlafaxine group at week 1 were (85.19%, 67.53%)
      vs (84.62%, 65.33%) DISCUSSION: The early improvement achieved within the first
      week treatment can predict a good 8-week treatment outcome in GAD patients.

PMID- 29193712
TI  - Internet addiction in college students and its relationship with cigarette
      smoking and alcohol use in Northeast China.

PMID- 29193713
TI  - Age-related clinical characteristics of major depressive disorder in Koreans:
      Results from the CRESCEND study.

PMID- 29193714
TI  - Influence of coping mechanisms on emotional problems among adolescents in
      Malaysian orphanages.

PMID- 29193715
TI  - Exploring Tetrathiafulvalene-Carbon Nanodot Conjugates in Charge Transfer
      Reactions.
AB  - Carbon nanodots (CNDs) were synthesized using low-cost and biocompatible starting
      materials such as citric acid/urea, under microwave irradiation, and constant
      pressure conditions. The obtained pressure-synthesized CNDs (pCNDs) were
      covalently modified with photo- and electroactive pi-extended tetrathiafulvalene
      (exTTF) by means of a two-step esterification reaction, affording pCND-exTTF. The
      electronic interactions between the pCNDs and exTTF were investigated in the
      ground and excited states. Ultrafast pump-probe experiments assisted in
      corroborating that charge separation governs the deactivation of photoexcited
      pCND-exTTF. These size-regular structures, as revealed by AFM, are stable
      electron donor-acceptor conjugates of interest for a better understanding of
      basic processes such as artificial photosynthesis, catalysis, and photovoltaics,
      involving readily available fluorescent nanodots.

PMID- 29193717
TI  - Is venous blood gas performed in the Emergency Department predictive of outcome
      during acute on chronic hypercarbic respiratory failure?
AB  - BACKGROUND: During acute on chronic hypercarbic respiratory failure (AHRF),
      arterial pH is associated with non-invasive ventilation (NIV) failure and
      mortality. Venous blood gas (VBG) has been proposed as a substitute for arterial
      blood gas, based on a good agreement between venous and arterial values. We
      assessed the predictive value of admission VBG on intubation rate, NIV failure
      and mortality during AHRF. METHODS: Retrospective chart review of inpatients
      admitted between 2009 and 2015 with AHRF who had VBG performed on admission.
      Demographic, clinical and biological data were collected throughout the hospital
      course. RESULTS: 196 patients were included and hospital survival was not
      significantly associated with initial venous pH, PCO2 or HCO3-. Patients
      requiring intubation had significantly lower venous pH [7.29 (7.24-7.33) vs 7.31
      (7.28-7.36), P = .04] while venous PCO2 and HCO3- did not differ as compared to
      non-intubated patients. Intubation within 48 h of admission was associated with
      significantly lower venous pH [7.28 (7.24-7.30) vs 7.32 (7.28-7.37), P = .002]
      and higher PCO2 [72 (63-92) mm Hg vs 62 (52-75) mm Hg, P = .04]. Among 69
      patients receiving NIV, there were no differences in venous pH [7.29 (7.25-7.31)
      vs 7.30 (7.27-7.35), P = .3] or PCO2 [68 (44-74) mm Hg vs 70 (55-97) mm Hg, P =
      .23] associated with subsequent intubation. Using c statistics, we observed poor
      performances of venous pH, PCO2 or HCO3- for prediction of NIV failure,
      intubation or hospital mortality. CONCLUSIONS: Our results do not support the use
      of VBG on admission as a predictor for NIV failure, intubation and mortality
      during AHRF.

PMID- 29193716
TI  - Acute inhibition of PMCA4, but not global ablation, reduces blood pressure and
      arterial contractility via a nNOS-dependent mechanism.
AB  - Cardiovascular disease is the world's leading cause of morbidity and mortality,
      with high blood pressure (BP) contributing to increased severity and number of
      adverse outcomes. Plasma membrane calcium ATPase 4 (PMCA4) has been previously
      shown to modulate systemic BP. However, published data are conflicting, with both
      overexpression and inhibition of PMCA4 in vivo shown to increase arterial
      contractility. Hence, our objective was to determine the role of PMCA4 in the
      regulation of BP and to further understand how PMCA4 functionally regulates BP
      using a novel specific inhibitor to PMCA4, aurintricarboxylic acid (ATA). Our
      approach assessed conscious BP and contractility of resistance arteries from
      PMCA4 global knockout (PMCA4KO) mice compared to wild-type animals. Global
      ablation of PMCA4 had no significant effect on BP, arterial structure or isolated
      arterial contractility. ATA treatment significantly reduced BP and arterial
      contractility in wild-type mice but had no significant effect in PMCA4KO mice.
      The effect of ATAin vivo and ex vivo was abolished by the neuronal nitric oxide
      synthase (nNOS) inhibitor Vinyl-l-NIO. Thus, this highlights differences in the
      effects of PMCA4 ablation and acute inhibition on the vasculature. Importantly,
      for doses here used, we show the vascular effects of ATA to be specific for PMCA4
      and that ATA may be a further experimental tool for elucidating the role of
      PMCA4.

PMID- 29193720
TI  - 2017 In reflection.

PMID- 29193721
TI  - Evaluation of an integrated primary care-led dementia shared care program in
      Singapore: An effectiveness and cost-effectiveness study.
AB  - AIM: With an aging Singapore population, there is an increasing demand for
      dementia care. The present study aimed to evaluate the effectiveness and cost
      effectiveness of the Primary Care Dementia Clinic (PCDC) in comparison with the
      Memory Clinic (MC; hospital-based) and other polyclinics. METHODS: A quasi
      experimental design was implemented. Effectiveness of PCDC was assessed through
      caregiver satisfaction, quality of life (caregiver-rated) and adverse events
      rates. Quality-of-Life measures using the EuroQol 5 Dimension Questionnaire (EQ
      5D) at baseline, 6 months and 12 months was assessed. Costs were calculated from
      a societal perspective. The incremental cost-effectiveness of the PCDC was
      compared with MC and other polyclinics. RESULTS: The present study showed that
      quality of life and the rate of adverse events at 12 months were similar between
      the three groups. Caregiver satisfaction at 12 months was higher in the PCDC
      group when compared with other polyclinics. There were no observed differences in
      societal cost between the three groups. At 6-month follow up, direct medical
      costs for PCDC were significantly lower that of other polyclinics. At 12-month
      follow up, PCDC patients had higher Quality Adjusted Life Years (QALYs) compared
      with the MC group. CONCLUSION: PCDC provided effective care, similar to care at
      MC and better than care at other polyclinics. Caregiver satisfaction was higher
      for the PCDC group, and PCDC patients had lower direct medical costs at 6-month
      follow up. Given these findings, adopting a PCDC model in other polyclinics in
      Singapore can be beneficial for optimal right siting of patients. Geriatr
      Gerontol Int 2018; 18: 479-486.

PMID- 29193722
TI  - F2 screen, inheritance and cross-resistance of field-derived Vip3A resistance in
      Spodoptera frugiperda (Lepidoptera: Noctuidae) collected from Louisiana, USA.
AB  - BACKGROUND: Fall armyworm, Spodoptera frugiperda, is a target pest of the Vip3A
      protein used in pyramided Bt corn and cotton in the USA. In this study, we
      provide the first documentation of a resistance allele conferring Vip3A
      resistance in a field-derived population of S. frugiperda from the USA, and
      characterize its inheritance and cross-resistance. RESULTS: An F2 screen with 104
      two-parent families generated from a field collection of S. frugiperda in
      Louisiana, USA, resulted in one family carrying a Vip3A resistance allele. The
      Vip3A-resistant strain (RR) derived from the two-parent family showed a high
      level of resistance to Vip3A in both diet and whole-plant bioassays, with a
      resistance ratio of >632.0-fold relative to a susceptible population (SS) based
      on diet-overlay bioassays. The inheritance of Vip3A resistance was monogenic,
      autosomal and recessive. Furthermore, the Vip3A resistance conferred no cross
      resistance to Cry1F, Cry2Ab2 or Cry2Ae purified proteins, with resistance ratios
      of 3.5, 5.0 and 1.1, respectively. CONCLUSION: These findings provide valuable
      information for characterizing Vip3A resistance, resistance monitoring, and
      developing effective resistance management strategies for the sustainable use of
      the Vip3A technology. (c) 2017 Society of Chemical Industry.

PMID- 29193724
TI  - Reverse Translation in Advancing Pharmacotherapy in Pediatric Rheumatology: A
      Logical Approach in Rare Diseases with Limited Resources.

PMID- 29193723
TI  - TRAF6 regulates tumour metastasis through EMT and CSC phenotypes in head and neck
      squamous cell carcinoma.
AB  - Epithelial-mesenchymal transition (EMT) is associated with metastasis formation,
      generation and maintenance of cancer stem cells (CSCs). However, the regulatory
      mechanisms of CSCs have not been clarified. This study aims to investigate the
      role of TNF receptor-associated factor 6 (TRAF6) on EMT and CSC regulation in
      squamous cell carcinoma of head and neck (SCCHN). We found TRAF6 was
      overexpressed in human SCCHN tissues, and high TRAF6 expression was associated
      with lymphatic metastasis and resulted in poor prognosis in patients with SCCHN.
      In addition, elevated TRAF6 expression was observed in several HNSCC cell lines,
      and wound healing and transwell assay results showed that TRAF6 knockdown
      inhibited the migration and invasion ability of the SCCHN cells. Moreover, the
      expression of Vimentin, Slug and N-cadherin was down-regulated and that of E
      cadherin was elevated after TRAF6 knockdown but decreased by transforming growth
      factor beta 1 (TGF-beta1) and CAL27 similar to mesenchymal cells formed after TGF
      beta1 induction. In addition, the expression levels of CD44, ALDH1, KLF4 and SOX2
      were inhibited after TRAF6 knockdown, and the anchor-dependent colony formation
      number and sphere number were remarkably reduced. Flow cytometry showed TRAF6
      knockdown reduced ALDH1-positive cancer stem cells. We also demonstrated that
      TRAF6 is closely associated with EMT process and cancer stem cells using a
      Tgfbr1/Pten 2cKO mice SCCHN model and human SCCHN tissue microarray. Our findings
      indicate that TRAF6 plays a role in EMT phenotypes, the generation and
      maintenance of CSCs in SCCHN, suggesting that TRAF6 is a potential therapeutic
      target for SCCHN.

PMID- 29193725
TI  - Opportunities and challenges for harvest weed seed control in global cropping
      systems.
AB  - The opportunity to target weed seeds during grain harvest was established many
      decades ago following the introduction of mechanical harvesting and the
      recognition of high weed-seed retention levels at crop maturity; however, this
      opportunity remained largely neglected until more recently. The introduction and
      adoption of harvest weed seed control (HWSC) systems in Australia has been in
      response to widespread occurrence of herbicide-resistant weed populations. With
      diminishing herbicide resources and the need to maintain highly productive
      reduced tillage and stubble-retention practices, growers began to develop systems
      that targeted weed seeds during crop harvest. Research and development efforts
      over the past two decades have established the efficacy of HWSC systems in
      Australian cropping systems, where widespread adoption is now occurring. With
      similarly dramatic herbicide resistance issues now present across many of the
      world's cropping regions, it is timely for HWSC systems to be considered for
      inclusion in weed-management programs in these areas. This review describes HWSC
      systems and establishing the potential for this approach to weed control in
      several cropping regions. As observed in Australia, the inclusion of HWSC systems
      can reduce weed populations substantially reducing the potential for weed
      adaptation and resistance evolution. (c) 2017 Society of Chemical Industry.

PMID- 29193726
TI  - Dihydroartemisinin up-regulates VE-cadherin expression in human renal glomerular
      endothelial cells.
AB  - The antimalarial agent dihydroartemisinin (DHA) has been shown to be anti
      inflammatory. In this study, we found that DHA increased the expression of the
      junctional protein vascular endothelial (VE)-cadherin in human renal glomerular
      endothelial cells. In addition, DHA inhibited TGF-beta RI-Smad2/3 signalling and
      its downstream effectors SNAIL and SLUG, which repress VE-cadherin gene
      transcription. Correspondingly, DHA decreased the binding of SNAIL and SLUG to
      the VE-cadherin promoter. Together, our results suggest an effect of DHA in
      regulating glomerular permeability by elevation of VE-cadherin expression.

PMID- 29193727
TI  - General and Facile Route to Isomerically Pure Tricyclic Peptides Based on
      Templated Tandem CLIPS/CuAAC Cyclizations.
AB  - We report a one-pot ligation/cyclization technology for the rapid and clean
      conversion of linear peptides into tricyclic peptides that is based on using
      tetravalent scaffolds containing two benzyl bromide and two alkyne moieties.
      These react via CLIPS/CuAAC reactions with cysteines and azides in the peptide.
      Flexibility in the scaffolds is key to the formation of isomerically pure
      products as the flexible scaffolds T41 and T42 mostly promote the formation of
      single isomeric tricycles while the rigid scaffolds T43 and T44 do not yield
      clean products. There seems to be no limitation to the number and types of amino
      acids present as 18 canonical amino acids were successfully implemented. We also
      observed that azides at the peptide termini and cysteine residues in the center
      gave better results than compounds with the functional groups placed the other
      way round.

PMID- 29193728
TI  - Cause of stillbirth reporting.

PMID- 29193729
TI  - FHL2 promotes tubular epithelial-to-mesenchymal transition through modulating
      beta-catenin signalling.
AB  - beta-Catenin signalling plays an important role in regulating tubular epithelial
      to-mesenchymal transition (EMT), an indispensable programme for driving renal
      fibrosis. As an adapter protein, four and a half LIM domain protein 2 (FHL2) acts
      as a coregulator of beta-catenin in several other cell types. To determine
      whether FHL2 affects beta-catenin signalling and thus is involved in tubular EMT,
      we examined its expression and function in the process of TGF-beta1-induced EMT.
      FHL2 mRNA and protein were induced by TGF-beta1 in rat tubular epithelial cells
      (NRK-52E), an effect that intracellular Smad signalling was required. Ectopic
      expression of FHL2 inhibited E-cadherin and enhanced alpha-smooth muscle actin
      (alpha-SMA) and fibronectin expression, whereas knockdown of FHL2 partially
      restored E-cadherin and reduced alpha-SMA and fibronectin induction stimulated by
      TGF-beta1. Overexpression of FHL2 increased beta-catenin dephosphorylation
      (Ser37/Thr41), nuclear translocation and beta-catenin-mediated transcription and
      up-regulated expression of beta-catenin target, EMT-related genes, such as Snail,
      Twist, vimentin, plasminogen activator inhibitor-1 and matrix metalloproteinase
      7. Conversely, knockdown of FHL2 increased beta-catenin phosphorylation
      (Ser33/37/Thr41), decreased its nuclear translocation and inhibited beta-catenin
      mediated transcription and target genes expression. TGF-beta1 induced a FHL2/beta
      catenin interaction in NRK-52E cells, especially in the nuclei. In a mouse model
      of obstructive nephropathy, FHL2 mRNA and protein were induced in a time
      dependent fashion, and the extent and pattern of renal beta-catenin activation
      were positively correlated with FHL2 induction. Collectively, this study suggests
      that FHL2, via modulating beta-catenin signalling, may implicate in regulation of
      TGF-beta1-mediated tubular EMT and could be a potential therapeutic target for
      fibrotic kidney disease.

PMID- 29193731
TI  - Antarctic bacteria: An annotated selection of World Wide Web sites relevant to
      the topics in environmental microbiology.

PMID- 29193730
TI  - The 3p14.2 tumour suppressor ADAMTS9 is inactivated by promoter CpG methylation
      and inhibits tumour cell growth in breast cancer.
AB  - Chromosome region 3p12-14 is an important tumour suppressor gene (TSG) locus for
      multiple cancers. ADAMTS9, a member of the metalloprotease large family, has been
      identified as a candidate 3p14.2 TSG inactivated by aberrant promoter CpG
      methylation in several carcinomas, but little known about its expression and
      function in breast cancer. In this report, ADAMTS9 expression and methylation was
      analysed in breast cancer cell lines and tissue samples. ADAMTS9 RNA was
      significantly down-regulated in breast cancer cell lines (6/8). After treating
      the cells with demethylation agent Aza and TSA, ADAMTS9 expression was
      dramatically increased. Bisulphite genomic sequencing and methylation-specific
      PCR detected promoter methylation, which was associated with decreased ADAMTS9
      expression. Hypermethylation was also detected in 130/219 (59.4%) of primary
      tumours but only in 4.5% (2/44) of paired surgical margin tissues. Ectopic
      expression of ADAMTS9 in tumor cells induced significant growth suppression, cell
      cycle arrest at the G0/G1 phase, enhanced apoptosis and reduced cell migration
      and invasion. Conditioned culture medium from ADAMTS9-transfected BT549 cells
      markedly disrupted tube formation ability of human umbilical vein endothelial
      cell (HUVEC) in Matrigel. Furthermore, ADAMTS9 inhibited AKT signaling and its
      downstream targets (MDM2, p53, p21, p27, E-cadherin, VIM, SNAIL, VEGFA, NFkappaB
      p65 and MMP2). In addition, we demonstrated, for the first time, that ADAMTS9
      inhibits AKT signaling, through suppressing its upstream activators EGFR and
      TGFbeta1/TbetaR(I/II) in breast cancer cells. Our results suggest that ADAMTS9 is
      a TSG epigenetically inactivated in breast cancer, which functions through
      blocking EGFR- and TGFbeta1/TbetaR(I/II)-activated AKT signaling.

PMID- 29193732
TI  - Energy and Optoelectronic Related Nanomaterials and Applications.

PMID- 29193734
TI  - Community intervention to increase neighborhood social network among Japanese
      older adults.
AB  - AIM: Strengthening neighborhood social networks is important for promoting health
      among older adults. However, effective intervention strategies aimed at
      increasing older adults' social networks have not yet been established. The
      present study examined whether a university-led community intervention that
      provided communication opportunities could increase older Japanese adults'
      neighborhood social networks. METHODS: The present study used a quasi
      experimental design. Before the intervention, using postal mail, we carried out a
      baseline questionnaire survey that was sent to all people living in the
      Tsurukabuto community aged >=60 years (n = 1769), of whom 1068 responded. For the
      community intervention, 18 event-based programs were provided over the course of
      1 year at Kobe University. Academic staff at Kobe University organized all the
      programs. During the program, social interactions among participants were
      promoted. A follow-up survey was distributed to those who responded to the
      baseline survey, and 710 individuals answered the question about their
      participation in the intervention programs (138 respondents were participants,
      572 were non-participants). The neighborhood social network was measured in both
      the baseline and follow-up surveys. RESULTS: Analysis of covariance showed that
      the changes in neighborhood social network among participants in the program was
      significantly higher than the changes among non-participants (P = 0.046) after
      adjusting for the baseline score of social network. CONCLUSIONS: The present
      study found that participants of the intervention expanded their neighborhood
      social network, but non-participants did not. This finding shows that community
      interventions using university resources could increase older adults'
      neighborhood social networks. Geriatr Gerontol Int 2018; 18: 462-469.

PMID- 29193733
TI  - Overexpression of the class I homeodomain transcription factor TaHDZipI-5
      increases drought and frost tolerance in transgenic wheat.
AB  - Characterization of the function of stress-related genes helps to understand the
      mechanisms of plant responses to environmental conditions. The findings of this
      work defined the role of the wheat TaHDZipI-5 gene, encoding a stress-responsive
      homeodomain-leucine zipper class I (HD-Zip I) transcription factor, during the
      development of plant tolerance to frost and drought. Strong induction of TaHDZipI
      5 expression by low temperatures, and the elevated TaHDZipI-5 levels of
      expression in flowers and early developing grains in the absence of stress,
      suggests that TaHDZipI-5 is involved in the regulation of frost tolerance at
      flowering. The TaHDZipI-5 protein behaved as an activator in a yeast
      transactivation assay, and the TaHDZipI-5 activation domain was localized to its
      C-terminus. The TaHDZipI-5 protein homo- and hetero-dimerizes with related
      TaHDZipI-3, and differences between DNA interactions in both dimers were
      specified at 3D molecular levels. The constitutive overexpression of TaHDZipI-5
      in bread wheat significantly enhanced frost and drought tolerance of transgenic
      wheat lines with the appearance of undesired phenotypic features, which included
      a reduced plant size and biomass, delayed flowering and a grain yield decrease.
      An attempt to improve the phenotype of transgenic wheat by the application of
      stress-inducible promoters with contrasting properties did not lead to the
      elimination of undesired phenotype, apparently due to strict spatial requirements
      for TaHDZipI-5 overexpression.

PMID- 29193735
TI  - Shotgun label-free proteomic analysis for identification of proteins in HaCaT
      human skin keratinocytes regulated by the administration of collagen from soft
      shelled turtle.
AB  - Soft-shelled turtles (Pelodiscus sinensis) are widely distributed in some Asian
      countries, and we previously reported that soft-shelled turtle tissue could be a
      useful material for collagen. In the present study, we performed shotgun liquid
      chromatography (LC)/mass spectrometry (MS)-based global proteomic analysis of
      collagen-administered human keratinocytes to examine the functional effects of
      collagen from soft-shelled turtle on human skin. Using a semiquantitative method
      based on spectral counting, we were able to successfully identify 187 proteins
      with expression levels that were changed more than twofold by the administration
      of collagen from soft-shelled turtle. Based on Gene Ontology analysis, the
      functions of these proteins closely correlated with cell-cell adhesion. In
      addition, epithelial-mesenchymal transition was induced by the administration of
      collagen from soft-shelled turtle through the down-regulation of E-cadherin
      expression. Moreover, collagen-administered keratinocytes significantly
      facilitated wound healing compared with nontreated cells in an in vitro scratch
      wound healing assay. These findings suggest that collagen from soft-shelled
      turtle provides significant benefits for skin wound healing and may be a useful
      material for pharmaceuticals and medical care products. (c) 2017 The Authors
      Journal of Biomedical Materials Research Part B: Applied Biomaterials Published
      by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2403
      2413, 2018.

PMID- 29193737
TI  - Laboratory testing in patients treated with direct oral anticoagulants: a
      practical guide for clinicians.
AB  - Click to hear Dr Baglin's perspective on the role of the laboratory in treatment
      with new oral anticoagulants SUMMARY: One of the key benefits of the direct oral
      anticoagulants (DOACs) is that they do not require routine laboratory monitoring.
      Nevertheless, assessment of DOAC exposure and anticoagulant effects may become
      useful in various clinical scenarios. The five approved DOACs (apixaban,
      betrixaban, dabigatran etexilate, edoxaban and rivaroxaban) have different
      characteristics impacting assay selection and the interpretation of results. This
      article provides an updated overview on (i) which test to use (and their
      advantages and limitations), (ii) when to assay DOAC levels, (iii) how to
      interpret the results relating to bleeding risk, emergency situations and
      perioperative management, and (iv) what is the impact of DOACs on routine and
      specialized coagulation assays. Assays for anti-Xa or anti-IIa activity are the
      preferred methods when quantitative information is useful, although the
      situations in which to test for DOAC levels are still debated. Different reagent
      sensitivities and variabilities in laboratory calibrations impact assay results.
      International calibration standards for all specific tests for each DOAC are
      needed to reduce the inter-laboratory variability and allow inter-study
      comparisons. The impact of the DOACs on hemostasis testing may cause false
      positive or false-negative results; however, these can be minimized by using
      specific assays and collecting blood samples at trough concentrations. Finally,
      prospective clinical trials are needed to validate the safety and efficacy of
      proposed laboratory thresholds in relation to clinical decisions. We offer
      recommendations on the tests to use for measuring DOACs and practical guidance on
      laboratory testing to help patient management and avoid diagnostic errors.

PMID- 29193736
TI  - Development of interstitial cells of Cajal in the human digestive tract as the
      result of reciprocal induction of mesenchymal and neural crest cells.
AB  - Neural crest cells (NCC) can migrate into different parts of the body and express
      their strong inductive potential. In addition, they are multipotent and are able
      to differentiate into various cell types with diverse functions. In the primitive
      gut, NCC induce differentiation of muscular structures and interstitial cells of
      Cajal (ICC), and they themselves differentiate into the elements of the enteric
      nervous system (ENS), neurons and glial cells. ICC develop by way of mesenchymal
      cell differentiation in the outer parts of the primitive gut wall around the
      myenteric plexus (MP) ganglia, with the exception of colon, where they appear
      simultaneously also at the submucosal border of the circular muscular layer
      around the submucosal plexus (SMP) ganglia. However, in a complex process of
      reciprocal induction of NCC and local mesenchyma, c-kit positive precursors are
      the first to differentiate, representing probably the common precursors of ICC
      and smooth muscle cells (SMC). C-kit positive precursors could represent a key
      impact factor regarding the final differentiation of NCC into neurons and glial
      cells with neurons subsequently excreting stem cell factor (SCF) and other
      signalling molecules. Under the impact of SCF, a portion of c-kit positive
      precursors lying immediately around the ganglia differentiate into ICC, while the
      rest differentiate into SMC.

PMID- 29193738
TI  - Cooperative role of the glucagon-like peptide-1 receptor and beta3-adrenergic
      mediated signalling on fat mass reduction through the downregulation of
      PKA/AKT/AMPK signalling in the adipose tissue and muscle of rats.
AB  - AIM: To explore the cooperation of GLP-1 receptor and beta3-adrenergic receptor
      (beta3-AR)-mediated signalling in the control of fat mass/feeding behaviour by
      studying the effects of a combined therapy composed of the GLP-1R agonist
      liraglutide and the beta3-AR agonist CL316243. METHODS: The study included the
      analysis of key mechanisms regulating lipid/cholesterol metabolism, and
      thermogenesis in brown (BAT) and epididymal white (eWAT) adipose tissues,
      abdominal muscle and liver of male rats. RESULTS: CL316243 (1 mg kg-1 ) and
      liraglutide (100 MUg kg-1 ) co-administration over 6 days potentiated an overall
      negative energy balance (reduction in food intake, body weight gain, fat/non-fat
      mass ratio, liver fat content, and circulating levels of non-essential fatty
      acids, triglycerides, very low-density lipoprotein-cholesterol and leptin). These
      effects were accompanied by increased plasma levels of insulin and IL6. We also
      observed increased gene expression of uncoupling proteins regulating
      thermogenesis in BAT/eWAT (Ucp1) and muscle (Ucp2/3). Expression of transcription
      factor and enzymes involved either in de novo lipogenesis (Chrebp, Acaca, Fasn,
      Scd1, Insig1, Srebp1) or in fatty acid beta-oxidation (Cpt1b) was enhanced in
      eWAT and/or muscle but decreased in BAT. Pparalpha and Ppargamma, essentials in
      lipid flux/storage, were decreased in BAT/eWAT but increased in the muscle and
      liver. Cholesterol synthesis regulators (Insig2, Srebp2, Hmgcr) were particularly
      over-expressed in muscle. These GLP-1R/beta3-AR-induced metabolic effects were
      associated with the downregulation of cAMP-dependent signalling pathways
      (PKA/AKT/AMPK). CONCLUSION: Combined activation of GLP-1 and beta3-ARs potentiate
      changes in peripheral pathways regulating lipid/cholesterol metabolism in a
      tissue-specific manner that favours a switch in energy availability/expenditure
      and may be useful for obesity treatment.

PMID- 29193739
TI  - Influence of no-tillage versus tillage system on common vole (Microtus arvalis)
      population density.
AB  - BACKGROUND: While the 'no-tillage' management system generally improves soil
      properties and helps to control arthropod pests, it may also intensify crop
      infestation by the common vole (Microtus arvalis Pallas). In this study, we
      evaluated the impact of soil management (no-tillage or tillage), crop and
      previous crop (winter wheat or winter rape), and season (spring or autumn) on
      common vole density using data from the Common Vole Monitoring Programme
      undertaken by the Plant Protection Service of the Czech Republic between 2000 and
      2009. RESULTS: Models predicted low mean values of vole infestation across
      management types, crops, and seasons. The untilled fields hosted significantly
      more voles than the tilled fields in spring but not in autumn. More common voles
      were found in winter rape than in winter wheat during both seasons. CONCLUSION:
      Recent studies suggest that no-tillage management is more profitable than tillage
      management as a result of its positive impact on soil properties and pest
      control. During periods of high vole infestation, however, tillage may constitute
      an alternative strategy for reducing yield losses. (c) 2017 Society of Chemical
      Industry.

PMID- 29193740
TI  - Viral internal ribosomal entry sites: four classes for one goal.
AB  - To ensure efficient propagation, viruses need to rapidly produce viral proteins
      after cell entrance. Since viral genomes do not encode any components of the
      protein biosynthesis machinery, viral proteins must be produced by the host cell.
      To hi-jack the host cellular translation, viruses use a great variety of distinct
      strategies. Many single-stranded positive-sensed RNA viruses contain so-called
      internal ribosome entry sites (IRESs). IRESs are structural RNA motifs that have
      evolved to specific folds that recruit the host ribosomes on the viral coding
      sequences in order to synthesize viral proteins. In host canonical translation,
      recruitment of the translation machinery components is essentially guided by the
      5' cap (m7 G) of mRNA. In contrast, IRESs are able to promote efficient ribosome
      assembly internally and in cap-independent manner. IRESs have been categorized
      into four classes, based on their length, nucleotide sequence, secondary and
      tertiary structures, as well as their mode of action. Classes I and II require
      the assistance of cellular auxiliary factors, the eukaryotic intiation factors
      (eIF), for efficient ribosome assembly. Class III IRESs require only a subset of
      eIFs whereas Class IV, which are the more compact, can promote translation
      without any eIFs. Extensive functional and structural investigations of IRESs
      over the past decades have allowed a better understanding of their mode of action
      for viral translation. Because viral translation has a pivotal role in the
      infectious program, IRESs are therefore attractive targets for therapeutic
      purposes. WIREs RNA 2018, 9:e1458. doi: 10.1002/wrna.1458 This article is
      categorized under: Translation > Ribosome Structure/Function Translation >
      Translation Mechanisms RNA Interactions with Proteins and Other Molecules > RNA
      Protein Complexes.

PMID- 29193742
TI  - Development of a LC-MS/MS method for the determination of isomeric glutamyl
      peptides in food ingredients.
AB  - A liquid chromatography with tandem mass spectrometry method was developed for
      the determination of 27 glutamyl di- and tripeptides in food ingredients. Such
      compounds are of importance for the food industry, as they can modulate the
      perception of basic tastes (sweet, salty, and umami). Due to their high polarity,
      the hydrophilic interaction chromatography mode was selected to have sufficient
      retention on the column and the best separation was obtained on an amide hybrid
      silica stationary phase packed with 1.7 MUm particles. Thorough optimization of
      the mobile phase was performed as the start-composition had to be free of
      ammonium to avoid on-column cis-trans isomerization of the first eluting proline
      dipeptide. A baseline separation was achieved for all alpha and gamma isomers
      whereas only a partial resolution was obtained for gamma-Glu-Leu and gamma-Glu
      Ile, for which only the position of a methyl group differs. A fast sample
      preparation, based on successive dilutions, was performed before injection into
      the liquid chromatography with tandem mass spectrometry system. The developed
      method was then applied for the semi-quantification of glutamyl di- and tri
      peptides in four different food ingredients. The methodology will further support
      the optimization of production processes to select the conditions for which the
      peptide concentrations would be the highest.

PMID- 29193741
TI  - Energy Expenditure and Hormone Responses in Humans After Overeating High-Fructose
      Corn Syrup Versus Whole-Wheat Foods.
AB  - OBJECTIVE: This study sought to understand how the dietary source of
      carbohydrates, either high-fructose corn syrup (HFCS) or complex carbohydrates,
      affects energy expenditure (EE) measures, appetitive sensations, and hormones
      during 24 hours of overfeeding. METHODS: Seventeen healthy participants with
      normal glucose regulation had 24-hour EE measures and fasting blood and 24-hour
      urine collection during four different 1-day diets, including an energy-balanced
      diet, fasting, and two 75% carbohydrate diets (5% fat) given at 200% of energy
      requirements with either HFCS or whole-wheat foods as the carbohydrate source. In
      eight volunteers, hunger was assessed with visual analog scales the morning after
      the diets. RESULTS: Compared with energy balance, 24-hour EE increased 12.8% +/-
      6.9% with carbohydrate overfeeding (P < 0.0001). No differences in 24-hour EE or
      macronutrient utilization were observed between the two high-carbohydrate diets;
      however, sleeping metabolic rate was higher after the HFCS diet (Delta = 35 +/-
      48 kcal [146 +/- 200 kJ]; P = 0.01). Insulin, ghrelin, and triglycerides
      increased the morning after both overfeeding diets. Urinary cortisol
      concentrations (82.8 +/- 35.9 vs. 107.6 +/- 46.9 nmol/24 h; P = 0.01) and morning
      after hunger scores (Delta = 2.4 +/- 2.0 cm; P = 0.01) were higher with HFCS
      overfeeding. CONCLUSIONS: The dietary carbohydrate source while overeating did
      not affect 24-hour EE, but HFCS overconsumption may predispose individuals to
      further overeating due to increased glucocorticoid release and increased hunger
      the following morning.

PMID- 29193743
TI  - Development of a fidelity scale for Danish specialized early interventions
      service.
AB  - BACKGROUND: The efficacy of the Specialized Early Intervention (SEI) treatment in
      Denmark, the OPUS treatment, has in a randomized clinical trial proved to be very
      effective compared to treatment as usual, and the dissemination of SEI services
      is increasing in Denmark. A prerequisite for upholding positive effects along
      with creating new teams and preserving critical components is to ensure fidelity
      to the model. Currently there is no Danish fidelity scale for SEI services. AIM:
      To establish a fidelity scale for SEI teams, in a brief and easily manageable
      form, for the use of evaluating and assessing the critical components in Danish
      SEI services. METHOD: We identified essential evidence-based components of SEI
      services internationally and interviewed experts from five Danish SEI teams,
      using an adapted version of the Delphi Consensus method. RESULTS: An 18-point
      fidelity scale was constructed. The scale was divided into two dimensions: one
      relating to the structure of the SEI team and one relating to the character and
      content of the SEI treatment. Each component can be rated either 1 or 0 (1 point
      = fulfilling the requirements for the components; and 0 point = the requirements
      were not met). The maximum score was a total of 18 points with 5 of the
      components being mandatory. CONCLUSION: The development of the fidelity scale is
      an important tool for securing the quality of SEI treatment in Denmark.

PMID- 29193744
TI  - What are the position and power of supermarkets in the Australian food system,
      and the implications for public health? A systematic scoping review.
AB  - Supermarkets have been described as having unprecedented and disproportionate
      power in the food system. This scoping review synthesized the literature that
      describes the position and power of supermarkets in the Australian food system,
      and the implications for public health. A systematic search of peer-reviewed and
      grey literature identified 68 documents that described supermarket power.
      Implications for public health were also recorded. Data revealed that
      supermarkets hold a powerful position in the Australian food system, acting as
      the primary gatekeepers. Supermarkets have obtained instrumental, structural and
      discursive power from many sources that overlap and reinforce each other. Few
      positive public health impacts of supermarket power were identified, providing
      many opportunities for improvement in the domains of food governance, the food
      system and public health nutrition. There is very little public health research
      examining the impact of supermarket power in Australia. More research is needed,
      and examination of supermarket own brands is of particular importance owing to
      their pivotal role as a source of power and their potential to improve public
      health outcomes, such as obesity.

PMID- 29193745
TI  - United States news media and climate change in the era of US President Trump.
AB  - The Donald J Trump administration's strategy to disengage and downplay the Paris
      Climate Agreement will likely result in a slight decrease in the already low
      levels of US news media global warming coverage. This is because significant
      limitations with the news media's ability to adequately cover climate change
      predated the administration. First, studies indicate that advertising interests
      and editors have always challenged journalists' abilities to adequately report on
      climate change issues. Instead of climate change stories, editors often prefer
      more sensational topics that garner higher ratings and approval with advertisers.
      Second, the journalistic norm of balance and the role of sourcing give climate
      skeptics exceptional media exposure, which creates a "false balance" or
      equivalency between skeptics and scientists. Third, the massive power and
      influence of the fossil fuel industry's public relations arm has also had a
      tremendous impact on public (mis)understanding of climate change. Fourth, a trend
      toward declining climate change coverage and "climate silence" in US media is
      developing. Media corporations have substantially eliminated the number of
      environmental journalists that cover climate change. The overall effect of these
      limitations distorts public understanding of climate change and delays potential
      government action. Moving away from a predominantly commercial media system to
      one with a substantial noncommercial component can improve US journalism, whereas
      using advertising to increase rates for environmentally unsound products and
      services may also help mitigate global warming. Integr Environ Assess Manag
      2018;14:202-204. (c) 2018 SETAC.

PMID- 29193746
TI  - Dual-Functional Dextran-PEG Hydrogel as an Antimicrobial Biomedical Material.
AB  - Microbial infections continually present a major worldwide public healthcare
      threat, particularly in instances of impaired wound healing and biomedical
      implant fouling. The development of new materials with the desired antimicrobial
      property to avoid and treat wound infection is urgently needed in wound care
      management. This study reports a novel dual-functional biodegradable dextran
      poly(ethylene glycol) (PEG) hydrogel covalently conjugated with antibacterial
      Polymyxin B and Vancomycin (Vanco). The hydrogel is designed as a specialized
      wound dressing that eradicates existing bacteria and inhibits further bacteria
      growth, while, ameliorating the side effects of antibiotics and accelerating
      tissue repair and regeneration. The hydrogel exhibits potent antibacterial
      activities against both gram-negative bacteria Escherichia coli (E. coli) and
      gram-positive bacteria Staphylococcus aureus (S. aureus) with no observable
      toxicity to mouse fibroblast cell line NIH 3T3. These results demonstrate the
      immense potential of dextran-PEG hydrogel as a wound dressing healthcare material
      in efficiently controlling bacteria growth in complex biological systems.

PMID- 29193747
TI  - Single-Dose Bioequivalence of Two Mini Nicotine Lozenge Formulations.
AB  - Diverse nicotine replacement therapy options may improve consumer usage. This
      study was conducted to establish the bioequivalence of a new cherry-flavored mini
      lozenge with that of a currently marketed mint-flavored mini lozenge. The rate
      (Cmax ) and extent (AUC0-t ) of plasma nicotine absorption were compared after
      administration of 2- and 4-mg doses of each lozenge in healthy adult smokers (n =
      43). The bioequivalence of each respective dose was established based on the 90%
      confidence interval for the ratio of geometric means for both Cmax and AUC0-t
      lying within the range of 0.80 to 1.25. Adverse-event profiles were similar
      between formulations.

PMID- 29193748
TI  - Modulation of cell responses to Ag-(MeO2 MA-co-OEGMA): Effects of nanoparticle
      surface hydrophobicity and serum proteins on cellular uptake and toxicity.
AB  - Nanoparticle (NP) interactions with cellular systems are influenced by both NP
      physico-chemical properties and the presence of surface-bound proteins that are
      adsorbed in biological environments. Here, we characterize cellular responses to
      silver nanoparticles (AgNPs) functionalized with poly(di(ethylene glycol) methyl
      ether methacrylate-co-oligo(ethylene glycol) methyl methacrylate) (poly(MeO2 MAx 
      co-OEGMAy )) brushes with tunable hydrophobicity and explore how these responses
      are modulated by the presence or absence of serum proteins. Poly(MeO2 MAx -co
      OEGMAy ) with variable composition (5-10% OEGMA) was fabricated to elicit
      differential hydrophobicity at 37 degrees C for AgNPs capped with these
      copolymers. The increase in Ag-(MeO2 MAx -co-OEGMAy ) surface hydrophobicity from
      (x:y) = 90:10 to (x:y) = 95:5 led to enhanced cytotoxicity of L-929 fibroblasts
      and a concomitant increase in cell uptake and reactive oxygen species generation
      in the presence of serum proteins. These responses were attenuated significantly
      in serum-free environments. Broad inhibition of PI3 kinase-mediated endocytosis
      reduced both cell uptake and cytotoxicity in the presence or absence of serum
      proteins. In contrast, selective inhibition of clathrin- and caveolae-mediated
      endocytosis markedly decreased cell uptake and cytotoxicity in response to Ag
      (MeO2 MA95 -co-OEGMA5 ) exclusively in the presence of serum proteins, whereas
      cell responses to the more hydrophilic Ag-(MeO2 MA90 -co-OEGMA10 ) were less
      affected by the inhibition of these pathways with or without serum proteins. This
      study demonstrates an important role for both NP surface hydrophobicity and the
      presence of serum proteins in directing cell uptake and subsequent cellular
      responses, which we suggest has broad application in the design of polymer
      functionalized NPs for specific biological outcomes. (c) 2017 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 1061-1071, 2018.

PMID- 29193750
TI  - Development of a high-performance liquid chromatography method for the
      simultaneous determination of chiral impurities and assay of (S)-clopidogrel
      using a cellulose-based chiral stationary phase in methanol/water mode.
AB  - A simple reversed-phase high-performance liquid chromatography method for the
      chiral separation of the active pharmaceutical ingredient (S)-clopidogrel has
      been developed on the cellulose-based Chiralcel OJ-RH chiral stationary phase.
      The S enantiomer was baseline resolved from its R impurity (impurity C) with a
      mobile phase consisting of methanol/water (100:15) without any interference
      coming from the other two potential chiral impurities A and B. The enantio- and
      chemoselective method was partially validated and compared with that reported in
      the United States Pharmacopoeia for the drug product. The versatility of the
      Chiralcel OJ-RH allowed separating the enantiomers of the impurity B also under
      normal phase and setting up an efficient strategy to convert the racemic sample
      into the enantiomeric S form on a semipreparative scale.

PMID- 29193749
TI  - Clinical Implementation of Pharmacogenetic Testing in a Hospital of the Spanish
      National Health System: Strategy and Experience Over 3 Years.
AB  - In 2014, we established a pharmacogenetics unit with the intention of
      facilitating the integration of pharmacogenetic testing into clinical practice.
      This unit was centered around two main ideas: i) individualization of clinical
      recommendations, and ii) preemptive genotyping in risk populations. Our unit is
      based on the design and validation of a single nucleotide polymorphism (SNP)
      microarray, which has allowed testing of 180 SNPs associated with drug response
      (PharmArray), and clinical consultation regarding the results. Herein, we report
      our experience in integrating pharmacogenetic testing into our hospital and we
      present the results of the 2,539 pharmacogenetic consultation requests received
      over the past 3 years in our unit. The results demonstrate the feasibility of
      implementing pharmacogenetic testing in clinical practice within a national
      health system.

PMID- 29193752
TI  - The Proteomic Response of Bacillus pumilus Cells to Glucose Starvation.
AB  - Since starvation for carbon sources is a common condition for bacteria in nature
      and it can also occur in industrial fermentation processes due to mixing zones,
      knowledge about the response of cells to carbon starvation is beneficial. The
      preferred carbon source for bacilli is glucose. The response of Bacillus pumilus
      cells to glucose starvation using metabolic labeling and quantitative proteomics
      was analyzed. Glucose starvation led to an extensive reprogramming of the protein
      expression pattern in B. pumilus. The amounts of proteins of the central carbon
      metabolic pathways (glycolysis and TCC) remained stable in starving cells.
      Proteins for gluconeogenesis were found in higher amounts during starvation.
      Furthermore, many proteins involved in acquisition and usage of alternative
      carbon sources were present in elevated amounts in starving cells. Enzymes for
      fatty acid degradation and proteases and peptidases were also found in higher
      abundance when cells entered stationary phase. Among the proteins found in lower
      amounts were many enzymes involved in amino acid and nucleotide synthesis and
      several NRPS and PKS proteins.

PMID- 29193753
TI  - Safety and efficacy of the hybrid approach in coronary chronic total occlusion
      percutaneous coronary intervention: The Hybrid Video Registry.
AB  - OBJECTIVES: The aim of the Hybrid Video Registry (HVR) is to assess the acute
      safety and efficacy of the Hybrid Approach in comparison to other contemporary
      methods of CTO-PCI. BACKGROUND: Recently, multiple techniques in Percutaneous
      Coronary Intervention (PCI) for coronary Chronic Total Occlusions (CTO) have been
      synthesized into a method referred to as the "Hybrid Approach". METHODS: About
      194 video-taped timed live cases from CTO-PCI training workshops were analyzed by
      independent data abstractors and compared to three contemporary CTO-PCI
      registries stratified by case complexity based on the J-CTO score. RESULTS:
      Overall procedural success was 95% of all cases attempted with an excellent
      safety profile. In the most complex lesion subset, which made up 45% of all HVR
      cases, success was 92.8%, which was significantly higher than either the Royal
      Bromptom (78.9%), or Japanese-CTO (73.3%) registries, P = 0.04 Hybrid vs. Royal
      Brompton, P = 0.006 Hybrid vs. Japanese-CTO). The Hybrid Approach was also
      associated with shorter procedure times and lower contrast utilization.
      CONCLUSIONS: In a real world angiographic registry of complex CTOs, the Hybrid
      Approach to CTO-PCI is safe, and may be superior to other contemporary approaches
      to CTO intervention with respect to procedural success and efficiency among a
      diverse group of operators and lesion complexity. (c) 2017 Wiley Periodicals,
      Inc.

PMID- 29193754
TI  - Development and optimisation of a novel three-way extraction technique based on a
      combination of Soxhlet extraction, membrane assisted solvent extraction and a
      molecularly imprinted polymer using sludge polycyclic aromatic hydrocarbons as
      model compounds.
AB  - A novel technique that integrates extraction and clean-up into a single step
      format is reported as part of the search for new sample preparation techniques in
      the analysis of persistent organic pollutants from complex samples. This was
      achieved by combining the extraction efficiency of the Soxhlet extractor, the
      selectivity of a size exclusion membrane and the specificity of a molecularly
      imprinted polymer for the extraction of polycyclic aromatic hydrocarbons from
      wastewater sludge followed by quantitation using gas chromatography with time-of
      flight mass spectrometry. The approach is described as the Soxhlet extraction
      membrane-assisted solvent extraction molecularly imprinted polymer technique.
      This technique was optimised for various parameters such as extraction solvent,
      reflux time and membrane acceptor phase. The applicability of the developed
      technique was optimised using a wastewater sludge certified reference material
      and then tested on real wastewater sludge samples. The method detection limits
      ranged from 0.14 to 12.86 ng/g with relative standard deviation values for the
      extraction of the 16 US-EPA priority polycyclic aromatic hydrocarbons from
      wastewater sludge samples ranging from 0.78 to 18%. The extraction process was
      therefore reproducible and showed remarkable selectivity. The developed technique
      is a promising prospect that can be applied in the analysis of organic pollutants
      from complex solid samples.

PMID- 29193751
TI  - The triune of intestinal microbiome, genetics and inflammatory status and its
      impact on the healing of lower gastrointestinal anastomoses.
AB  - Gastrointestinal resections are a common operation and most involve an
      anastomosis to rejoin the ends of the remaining bowel to restore gastrointestinal
      (GIT) continuity. While most joins heal uneventfully, in up to 26% of patients
      healing fails and an anastomotic leak (AL) develops. Despite advances in surgical
      technology and techniques, the rate of anastomotic leaks has not decreased over
      the last few decades raising the possibility that perhaps we do not yet fully
      understand the phenomenon of AL and are thus ill-equipped to prevent it. As in
      all complex conditions, it is necessary to isolate each different aspect of
      disease for interrogation of its specific role, but, as we hope to demonstrate in
      this article, it is a dangerous oversimplification to consider any single aspect
      as the full answer to the problem. Instead, consideration of important individual
      observations in parallel could illuminate the way forward towards a possibly
      simple solution amidst the complexity. This article details three aspects that we
      believe intertwine, and therefore should be considered together in wound healing
      within the GIT during postsurgical recovery: the microbiome, the host genetic
      make-up and their relationship to the perioperative inflammatory status. Each of
      these, alone or in combination, has been linked with various states of health and
      disease, and in combining these three aspects in the case of postoperative
      recovery from bowel resection, we may be nearer an answer to preventing
      anastomotic leaks than might have been thought just a few years ago.

PMID- 29193755
TI  - Relationship between kidney findings and systemic vascular damage in elderly
      hypertensive patients without overt cardiovascular disease.
AB  - Few studies have investigated the influence of age on the relationships between
      systemic vascular damage, kidney dysfunction, and intrarenal hemodynamic changes
      in patients with hypertension without overt cardiovascular disease. The authors
      enrolled 126 elderly patients with hypertension (aged >=65 years) and 350
      nonelderly patients with hypertension (aged <65 years). Carotid intima-media
      thickness, renal resistive index, and aortic pulse wave velocity were performed
      in all patients. Elderly patients with hypertension had lower estimated
      glomerular filtration rates and higher albuminuria, renal resistive index,
      carotid intima-media thickness, and aortic pulse wave velocity compared with
      nonelderly patients with hypertension (P < .001). Carotid intima-media thickness
      independently correlated with renal resistive index and estimated glomerular
      filtration rate in nonelderly patients with hypertension, whereas it was
      significantly related to renal resistive index only in elderly patients with
      hypertension. Aortic pulse wave velocity was independently associated with
      albuminuria in nonelderly patients with hypertension, whereas it did not
      independently correlate with any indexes of renal damage in elderly patients with
      hypertension. Age is an important modifier of the relationships between renal
      function and renal hemodynamics with subclinical vascular involvement in elderly
      persons without cardiovascular disease.

PMID- 29193756
TI  - Investigating the cardiac pathology of SCO2-mediated hypertrophic cardiomyopathy
      using patients induced pluripotent stem cell-derived cardiomyocytes.
AB  - Mutations in SCO2 are among the most common causes of COX deficiency, resulting
      in reduced mitochondrial oxidative ATP production capacity, often leading to
      hypertrophic cardiomyopathy (HCM). To date, none of the recent pertaining reports
      provide deep understanding of the SCO2 disease pathophysiology. To investigate
      the cardiac pathology of the disease, we were the first to generate induced
      pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) from SCO2-mutated
      patients. For iPSC generation, we reprogrammed skin fibroblasts from two SCO2
      patients and healthy controls. The first patient was a compound heterozygote to
      the common E140K mutation, and the second was homozygote for the less common
      G193S mutation. iPSC were differentiated into cardiomyocytes through embryoid
      body (EB) formation. To test the hypothesis that the SCO2 mutation is associated
      with mitochondrial abnormalities, and intracellular Ca2+ -overload resulting in
      functional derangements and arrhythmias, we investigated in SCO2-mutated iPSC-CMs
      (compared to control cardiomyocytes): (i) the ultrastructural changes; (ii) the
      inotropic responsiveness to beta-adrenergic stimulation, increased [Ca2+ ]o and
      angiotensin-II (AT-II); and (iii) the Beat Rate Variability (BRV)
      characteristics. In support of the hypothesis, we found in the mutated iPSC-CMs
      major ultrastructural abnormalities and markedly attenuated response to the
      inotropic interventions and caffeine, as well as delayed afterdepolarizations
      (DADs) and increased BRV, suggesting impaired SR Ca2+ handling due to attenuated
      SERCA activity caused by ATP shortage. Our novel results show that iPSC-CMs are
      useful for investigating the pathophysiological mechanisms underlying the SCO2
      mutation syndrome.

PMID- 29193757
TI  - Effects of the Consumption of Milk Biofortified with Selenium, Vitamin E, and
      Different Fatty Acid Profile on Immune Response in the Elderly.
AB  - SCOPE: Nutrition is a major contributing factor for immunocompetence. The aim was
      to assess the immune status of older people after consuming milk produced by
      lactating cows fed with one of the following diets: control diet (C), C + vitamin
      E + selenium (C + A), C + sunflower oil (C + O), and C + sunflower oil + vitamin
      E + selenium (A + O). METHODS AND RESULTS: Sixty elderly people received one of
      these biofortified milks for 12 weeks. Immune response was assessed by
      measurement of the expression of COX-1, COX-2, MCP-1, PPAR (delta, alpha, and
      beta/delta) genes, neutrophil production of oxygen reactive species induced by
      immune complexes, neutrophil phagocytosis and lytic activity of the alternative
      pathway of the complement system, and cytokine levels. Variables were assessed
      before and after treatment. Our findings showed stability of some inflammatory
      mediators (complement activity and neutrophils burst) in treatment groups, except
      complement activity in C + A, and an increase of these markers in C, especially
      reactive oxygen species production and phagocytic activity. TNF-alpha was
      significantly increased in all groups. In C + A, IL-4 and IL-2 increased after
      treatment, and in the group that received the milk produced by cows fed with "O"
      diet, CCL20 and IL-27 increased. CONCLUSION: Overall, as compared to C, milk
      biofortification was associated with stabilization of the activity of alternative
      complement pathway and the neutrophils burst, and modulated different cytokines
      levels.

PMID- 29193758
TI  - Hemodynamic impact of pulmonary vasodilators on single ventricle physiology.
AB  - INTRODUCTION: The Fontan procedure is the palliative procedure for single
      ventricle physiology. Pulmonary resistance plays a key role in the success of
      this operation. There are conflicting data concerning the impact of pulmonary
      vasodilators on survival and functional capacity among Fontan patients. AIM: The
      aim of this retrospective, single-center, nonrandomized study was to investigate
      the potential effect of pulmonary vasodilators on pulmonary vasculature in Fontan
      patients. METHOD: Twenty-seven patients with single ventricle physiology were
      enrolled. Eighteen patients were treated with pulmonary vasodilators: 9 patients
      after Glenn procedure or just after the Fontan completion (Group A) and 9
      patients >5 years after Fontan completion (Group B). Nine patients after Glenn
      procedure were enrolled as a control group (Group C). The primary endpoint was to
      assess changes in hemodynamic profile and pulmonary branches' diameter after 2
      right heart catheterizations. Adverse events were recorded. RESULTS: Mean age +/-
      SD was 3.2 +/- 1.5 years (Group A), 26.8 +/- 12.7 years (Group B), and 3.1 +/-
      1.0 years (Group C). Patients included in Group A had reduced arterial compliance
      (34.3 +/- 15.4 vs 52.2 +/- 24.2 mm2 /[m2 *mm Hg]; P = .03) at baseline compared
      with Group C. After treatment, Nakata index and pulmonary compliance increased in
      patients treated with pulmonary vasodilators (Group A), while remaining stable in
      the control group (Nakata index: +26 +/- 24% vs -8 +/- 17%, P = .003; pulmonary
      compliance +80 +/- 49% vs -5 +/- 30%, P = .001). Similar results were found in
      Group B (Nakata index: pre-168.6 +/- 70.7 mm2 /m2 ; post-204.9 +/- 97.5 mm2 /m2 ;
      P = .026). CONCLUSIONS: Pulmonary vasodilators reduce pulmonary artery resistance
      and increase vascular compliance, pulmonary artery diameter, and cardiac output
      in Fontan patients. Therefore, pulmonary vasodilators may be used before the
      Fontan procedure in patients at high risk of Fontan procedure failure.

PMID- 29193759
TI  - Soil and Water Assessment Tool model predictions of annual maximum pesticide
      concentrations in high vulnerability watersheds.
AB  - Recent national regulatory assessments of potential pesticide exposure of
      threatened and endangered species in aquatic habitats have led to increased need
      for watershed-scale predictions of pesticide concentrations in flowing water
      bodies. This study was conducted to assess the ability of the uncalibrated Soil
      and Water Assessment Tool (SWAT) to predict annual maximum pesticide
      concentrations in the flowing water bodies of highly vulnerable small- to medium
      sized watersheds. The SWAT was applied to 27 watersheds, largely within the
      midwest corn belt of the United States, ranging from 20 to 386 km2 , and
      evaluated using consistent input data sets and an uncalibrated parameterization
      approach. The watersheds were selected from the Atrazine Ecological Exposure
      Monitoring Program and the Heidelberg Tributary Loading Program, both of which
      contain high temporal resolution atrazine sampling data from watersheds with
      exceptionally high vulnerability to atrazine exposure. The model performance was
      assessed based upon predictions of annual maximum atrazine concentrations in 1-d
      and 60-d durations, predictions critical in pesticide-threatened and endangered
      species risk assessments when evaluating potential acute and chronic exposure to
      aquatic organisms. The simulation results showed that for nearly half of the
      watersheds simulated, the uncalibrated SWAT model was able to predict annual
      maximum pesticide concentrations within a narrow range of uncertainty resulting
      from atrazine application timing patterns. An uncalibrated model's predictive
      performance is essential for the assessment of pesticide exposure in flowing
      water bodies, the majority of which have insufficient monitoring data for direct
      calibration, even in data-rich countries. In situations in which SWAT over- or
      underpredicted the annual maximum concentrations, the magnitude of the over- or
      underprediction was commonly less than a factor of 2, indicating that the model
      and uncalibrated parameterization approach provide a capable method for
      predicting the aquatic exposure required to support pesticide regulatory decision
      making. Integr Environ Assess Manag 2018;14:358-368. (c) 2017 The Authors.
      Integrated Environmental Assessment and Management published by Wiley
      Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry
      (SETAC).

PMID- 29193760
TI  - Measles vaccination status of nurses and associated factors during community
      measles outbreaks.
AB  - AIM: To identify the measles vaccination status of nurses, their knowledge and
      health beliefs about measles, and the associated factors that influence their
      measles vaccination status during a community measles outbreak in South Korea.
      METHODS: The participants were 156 nurses from four hospitals in a region where a
      community measles outbreak occurred. RESULTS: The measles vaccination rate of the
      nurses was 73.7%. The nurses' health belief score about measles was 2.44 out of 4
      and their knowledge score was 73.85 out of 100. The associated factors that
      influenced the nurses' measles vaccination status included their experience of
      caring for patients with measles and a low level of perceived barriers to
      vaccination. CONCLUSION: In order to encourage an increased measles vaccination
      rate in nurses, hospitals should screen susceptible nurses and offer vaccination.
      Effective measles vaccination campaigns and educational programs are also
      required in hospitals.

PMID- 29193761
TI  - Bismuth Vanadate Photoelectrodes with High Photovoltage as Photoanode and
      Photocathode in Photoelectrochemical Cells for Water Splitting.
AB  - Using dual-photoelectrode photoelectrochemical (PEC) devices based on earth
      abundant metal oxides for unbiased water splitting is an attractive means of
      producing green H2 fuel, but is challenging, owing to low photovoltages generated
      by PEC cells. This problem can be solved by coupling n-type BiVO4 with n-type Bi4
      V2 O11 to create a virtual p/n junction due to the formation of a hole-inversion
      layer at the semiconductor interface. Thus, photoelectrodes with high
      photovoltage outputs were synthesized. The photoelectrodes exhibited features of
      p- and n-type semiconductors when illuminated under an applied bias, suggesting
      their use as photoanode and photocathode in a dual-photoelectrode PEC cell. This
      concept was proved by connecting a 1 mol % W-doped BiVO4 /Bi4 V2 O11 photoanode
      with an undoped BiVO4 /Bi4 V2 O11 photocathode, which produced a high
      photovoltage of 1.54 V, sufficient to drive stand-alone water splitting with 0.95
      % efficiency.

PMID- 29193762
TI  - Semiconductor-Based Photoelectrochemical Conversion of Carbon Dioxide: Stepping
      Towards Artificial Photosynthesis.
AB  - The photoelectrochemical (PEC) carbon dioxide reduction process stands out as a
      promising avenue for the conversion of solar energy into chemical feedstocks,
      among various methods available for carbon dioxide mitigation. Semiconductors
      derived from cheap and abundant elements are interesting candidates for
      catalysis. Whether employed as intrinsic semiconductors or hybridized with
      metallic cocatalysts, biocatalysts, and metal molecular complexes, semiconductor
      photocathodes exhibit good performance and low overpotential during carbon
      dioxide reduction. Apart from focusing on carbon dioxide reduction materials and
      chemistry, PEC cells towards standalone devices that use photohybrid electrodes
      or solar cells have also been a hot topic in recent research. An overview of the
      state-of-the-art progress in PEC carbon dioxide reduction is presented and a deep
      understanding of the catalysts of carbon dioxide reduction is also given.

PMID- 29193764
TI  - The interstitium conducts extrarenal storage of sodium and represents a third
      compartment essential for extracellular volume and blood pressure homeostasis.
AB  - The role of salt in the pathogenesis of arterial hypertension is not well
      understood. According to the current understanding, the central mechanism for
      blood pressure (BP) regulation relies on classical studies linking BP and Na+
      balance, placing the kidney at the very centre of long-term BP regulation. To
      maintain BP homeostasis, the effective circulating fluid volume and thereby body
      Na+ content has to be maintained within very narrow limits. From recent work in
      humans and rats, the notion has emerged that Na+ could be stored somewhere in the
      body without commensurate water retention to buffer free extracellular Na+ and
      that previously unidentified extrarenal, tissue-specific regulatory mechanisms
      are operative regulating the release and storage of Na+ from a kidney-independent
      reservoir. Moreover, immune cells from the mononuclear phagocyte system not only
      function as local on-site sensors of interstitial electrolyte concentration, but
      also, together with lymphatics, act as systemic regulators of body fluid volume
      and BP. These studies have established new and unexpected targets in studies of
      BP control and thus the pathophysiology of hypertension: the
      interstitium/extracellular matrix of the skin, its inherent interstitial fluid
      and the lymphatic vasculature forming a vessel network in the interstitium.
      Aspects of the interstitium in relation to Na+ balance and hypertension are the
      focus of this review. Taken together, observations of salt storage in the skin to
      buffer free extracellular Na+ and macrophage modulation of the extracellular
      matrix and lymphatics suggest that electrolyte homeostasis in the body cannot be
      achieved by renal excretion alone, but also relies on extrarenal regulatory
      mechanisms.

PMID- 29193763
TI  - Identification of a novel RPGRIP1 mutation in an Iranian family with leber
      congenital amaurosis by exome sequencing.
AB  - Leber congenital amaurosis (LCA) is a heterogeneous, early-onset inherited
      retinal dystrophy, which is associated with severe visual impairment. We aimed to
      determine the disease-causing variants in Iranian LCA and evaluate the clinical
      implications. Clinically, a possible LCA disease was found through diagnostic
      imaging, such as fundus photography, autofluorescence and optical coherence
      tomography. All affected patients showed typical eye symptoms associated with LCA
      including narrow arterioles, blindness, pigmentary changes and nystagmus. Target
      exome sequencing was performed to analyse the proband DNA. A homozygous novel c.
      2889delT  (p.P963 fs) mutation in the RPGRIP1 gene was identified, which was
      likely the deleterious and pathogenic mutation in the proband. Structurally, this
      mutation lost a retinitis pigmentosa GTPase regulator (RPGR)-interacting domain
      at the C-terminus which most likely impaired stability in the RPGRIP1 with the
      distribution of polarised proteins in the cilium connecting process. Sanger
      sequencing showed complete co-segregation  in this pedigree. This study provides
      compelling evidence that the c. 2889delT  (p.P963 fs) mutation in the RPGRIP1
      gene works as a pathogenic mutation that contributes to the progression of LCA.

PMID- 29193766
TI  - Negative HBcAg in immunohistochemistry assay of liver biopsy is a predictive
      factor for the treatment of patients with nucleos(t)ide analogue therapy.
AB  - The hepatitis B core antigen (HBcAg) is an important target for antiviral
      response in chronic hepatitis B (CHB) patients. However, the correlation between
      HBcAg in the hepatocyte nucleus and nucleos(t)ide analogue (NA) therapeutic
      response is unclear. We sought to evaluate the role of HBcAg by analysing liver
      biopsies for viral response in NA-naive hepatitis B e antigen (HBeAg) positive
      (+) CHB patients via immunohistochemistry (IHC). A total of 48 HBcAg-negative (-)
      patients and 48 HBcAg (+) patients with matching baseline characteristics were
      retrospectively analysed for up to 288 weeks. Virological response (VR) rates of
      patients in the HBcAg (-) group were significantly higher at week 48 and 96 than
      the HBcAg (+) group (77.1% versus 45.8% at week 48, respectively, P = 0.002 and
      95.3% versus 83.3% at week 96, respectively, P = 0.045). The serological negative
      conversion rate of HBeAg was significantly higher in the HBcAg (-) than in the
      HBcAg (+) group from week 96 to 288 (35.4 % versus 14.6% at week 96,
      respectively, P = 0.018; 60.4% versus 14.6%, respectively, P < 0.001 at week 144;
      72.9% versus 35.4%, respectively, P < 0.001 at week 288). The cumulative
      frequencies of VR and lack of HBeAg were higher in the HBcAg (-) group (both P <
      0.05). Binary logistic regression analysis showed that HBcAg (-) was the
      predictor for the lack of HBeAg (OR 4.482, 95% CI: 1.58-12.68). In summary, the
      absence of HBcAg in the hepatocyte nucleus could be an independent predictor for
      HBeAg seroconversion rates during NA-naive treatment in HBeAg (+) CHB patients.

PMID- 29193765
TI  - Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome
      Measures in Rheumatology Consensus-Based Recommendations and Research Agenda for
      Use of Composite Measures and Treatment Targets in Psoriatic Arthritis.
AB  - OBJECTIVE: A meeting was convened by the Group for Research and Assessment of
      Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology
      (OMERACT) to further the development of consensus among physicians and patients
      regarding composite disease activity measures and targets in psoriatic arthritis
      (PsA). METHODS: Prior to the meeting, physicians and patients completed surveys
      on outcome measures. A consensus meeting of 26 rheumatologists, dermatologists,
      and patient research partners reviewed evidence on composite measures and
      potential treatment targets plus results of the surveys. The meeting consisted of
      plenary presentations, breakout sessions, and group discussions. International
      experts including members of GRAPPA and OMERACT were invited to the meeting,
      including the developers of all of the measures discussed. After discussions,
      participants voted on proposals for use, and consensus was established in a
      second survey. RESULTS: Survey results from 128 health care professionals and 139
      patients were analyzed alongside a systematic literature review summarizing
      evidence. A weighted vote was cast for composite measures. For randomized
      controlled trials, the most popular measures were the PsA disease activity score
      (40 votes) and the GRAPPA composite index (28 votes). For clinical practice, the
      most popular measures were an average of scores on 3 visual analog scales (45
      votes) and the disease activity in PsA score (26 votes). After discussion, there
      was no consensus on a composite measure. The group agreed that several composite
      measures could be used and that future studies should allow further validation
      and comparison. The group unanimously agreed that remission should be the ideal
      target, with minimal disease activity (MDA)/low disease activity as a feasible
      alternative. The target should include assessment of musculoskeletal disease,
      skin disease, and health-related quality of life. The group recommended a
      treatment target of very low disease activity (VLDA) or MDA. CONCLUSION:
      Consensus was not reached on a continuous measure of disease activity. In the
      interim, the group recommended several composites. Consensus was reached on a
      treatment target of VLDA/MDA. An extensive research agenda was composed and
      recommends that data on all PsA clinical domains be collected in ongoing studies.

PMID- 29193767
TI  - Empagliflozin decreases remnant-like particle cholesterol in type 2 diabetes
      patients with insulin resistance.
AB  - AIMS/INTRODUCTION: Remnant lipoproteins are thought to be atherogenic. Remnant
      like particle cholesterol (RLP-C), which reflects the levels of various kinds of
      remnant lipoproteins in the blood, has a significant correlation with insulin
      resistance. MATERIALS AND METHODS: In the present study, we measured the effect
      of empagliflozin (EMPA) on the levels of RLP-C, and investigated whether EMPA
      mediated change in RLP-C is associated with a change in insulin resistance in
      type 2 diabetes patients who have insulin resistance. RESULTS: Patients were
      allocated to receive a placebo (n = 51) or EMPA (n = 58) as an add-on treatment.
      Fasting blood samples were collected before and 12 weeks after this intervention.
      EMPA significantly decreased glycated hemoglobin, bodyweight, systolic blood
      pressure, plasma triglycerides, liver transaminases and estimated glomerular
      filtration rate, and increased high-density lipoprotein cholesterol. Furthermore,
      EMPA decreased RLP-C and homeostatic model assessment of insulin resistance. In
      the placebo group, there were no significant changes in these factors except for
      slight increases in liver transaminases. Multiple regression analysis showed that
      the change in homeostatic model assessment of insulin resistance (P = 0.0102) and
      the change in alanine aminotransferase (P = 0.0301) were significantly associated
      with the change in RLP-C in the EMPA group. The change in RLP-C significantly
      correlated with the change in homeostatic model assessment of insulin resistance
      (Pearson correlation coefficient 0.503, 95% confidence interval 0.199-0.719; P =
      0.00241). CONCLUSION: EMPA decreases RLP-C levels, which is closely associated
      with amelioration of insulin sensitivity in diabetes patients who have insulin
      resistance.

PMID- 29193768
TI  - Initial experience of sleeve lobectomy under complete video-assisted thoracic
      surgery.
AB  - PURPOSE: Review the initial results of a single-center complete video-assisted
      thoracoscopic surgery (VATS) sleeve lobectomy and discuss the key procedure of
      this operation, in addition to its safety and feasibility. METHODS:
      Retrospectively analyze the perioperative data of 11 patients who accepted
      complete VATS sleeve lobectomy between May 2013 and Jun 2017 in Peking University
      Third Hospital, try to evaluate the safety of this procedure. All the patients
      were followed up and their oncological recurrence and metastasis were observed,
      and feasibility of VATS sleeve lobectomy for lung cancer was evaluated. RESULTS:
      All of the 11 cases underwent complete VATS sleeve lobectomy successfully and
      there is no conversion to thoracotomy. The mean operative time was 338 min (range
      from 243 to 511 min), the mean time of bronchial anastomotic was 63 min (range
      from 40 to 96 min), the mean blood loss was 205 mL (range from 50 to 400 mL), and
      the mean number of lymph nodes dissected is 22.1. There was no other complication
      except one patient suffered from high-risk pulmonary embolism, and no anastomotic
      leakage and stricture was found. The mean hospital stay postoperation was 8.7
      days. The time of follow-up was between 2 and 38 months, only one out of the 11
      cases died of bone metastasis, and the other 10 survived till now. One of these
      10 patients had local recurrence 24 months after operation, and one suffered
      adenocarcinoma of esophageal-gastric junction at 15 months postoperation. The
      rest of eight patients all survived to June 2017 and no local recurrence and
      metastasis was found. The mean survival time was 14.8 months. CONCLUSION:
      Complete VATS sleeve lobectomy is a safe and feasible procedure, but the
      advantage of perioperative and long-term survival need prospective randomized
      controlled large sample trial to be confirmed.

PMID- 29193769
TI  - Inflammatory and Physiological Consequences of Debridement of Fibrous Tissue
      after Volumetric Muscle Loss Injury.
AB  - Volumetric muscle loss (VML) injuries present chronic loss of muscle fibers
      followed by expansive fibrotic tissue deposition. Regenerative medicine therapies
      are under development to promote regeneration. However, mitigation of the
      expansive fibrous tissue is required for integration with the remaining muscle.
      Using a porcine VML model, delayed debridement of injury fibrosis was performed 3
      months post-VML and observed for an additional 4 weeks. A second group underwent
      the initial VML and was observed for 4 weeks, allowing comparison of initial
      fibrosis formation and debrided groups. The following salient observations were
      made: (i) debridement neither exacerbated nor ameliorated strength deficits; (ii)
      debridement results in recurrent fibrotic tissue deposition of a similar
      magnitude and composition as acute VML injury; and (iii) similarly upregulated
      transcriptional fibrotic and transcriptional pathways persist 4 weeks after
      initial VML or delayed debridement. This highlights the need for future studies
      to investigate adjunctive antifibrotic treatments for the fibrosed musculature.

PMID- 29193770
TI  - Development of a clinical prediction model for the postthrombotic syndrome in a
      prospective cohort of patients with proximal deep vein thrombosis.
AB  - : Essentials We developed a prediction model for postthrombotic syndrome (PTS)
      after deep vein thrombosis (DVT). High risk predictors were iliac vein DVT,
      BMI>35 and moderate-severe Villalta category. Patients with a score >=4 had an
      odds ratio of 5.9 (95% CI 2.1-16.6) for PTS. SOX-PTS score may select DVT
      patients for close monitoring or aggressive strategies to treat DVT. SUMMARY:
      Background Postthrombotic syndrome (PTS) is a chronic complication that develops
      in 20-50% of patients after deep vein thrombosis (DVT). Although individual risk
      factors for PTS have been characterized, the ability to predict which DVT
      patients are likely to develop PTS remains limited. Objective To develop a
      clinical prediction score for PTS in patients with DVT. Methods The derivation
      cohort consisted of participants in the SOX Trial, a randomized double-blind
      placebo-controlled trial of elastic compression stockings versus placebo
      stockings worn for 2 years after DVT to prevent PTS in patients with a first
      proximal DVT, enrolled in 24 community and tertiary-care hospitals from 2004 to
      2010. Multivariable logistic regression analysis of baseline characteristics was
      performed. The outcome was the occurrence of PTS, diagnosed starting from 6
      months or later according to Ginsberg's criteria. Results Seven hundred and sixty
      two patients were included in the analysis. The median follow-up was 728 days.
      The model includes three independent predictors, and has a range of possible
      scores from 0 to 5. High-risk predictors were: index DVT in the iliac vein; body
      mass index of >= 35 kg m-2 ; and moderate-severe Villalta severity category at
      DVT diagnosis. As compared with patients with a score of 0, those with a score of
      >= 4 had an odds ratio of 5.9 (95% confidence interval 2.1-16.6) for developing
      PTS. Conclusions To our knowledge, this is the first clinical prediction score
      for PTS. We identified three independent predictors that, when combined,
      predicted PTS risk after a first proximal DVT. The SOX-PTS score requires
      external validation before it can be considered for clinical use.

PMID- 29193771
TI  - Transition of Akabane virus genogroups and its association with changes in the
      nature of disease in Japan.
AB  - Akabane virus (AKAV) is teratogenic to the foetus of domestic ruminants and
      causes a significant reproduction loss in cattle in Japan. In several past
      epizootics in cattle, AKAV was also associated with post-natal encephalomyelitis,
      mainly in calves and young stock. Previously analysed AKAV isolates in East Asia
      form two major clusters, genogroups I and II, with isolates involved in
      encephalomyelitis belonging mainly to the former. Between 2007 and 2013, AKAV
      epizootics were regularly observed in Japan during the summer/autumn season, and
      abnormal deliveries and post-natal encephalomyelitis caused by the virus in
      cattle were reported. During this period, 30 AKAV isolates were obtained from
      diseased and sentinel cattle, a piglet and Culicoides biting midges throughout
      Japan and were subjected to genetic comparison and phylogenetic analysis with
      previous isolates. In 2007, 2011 and 2013, AKAV belonging to genogroup I was
      identified in the central nervous systems of calves showing neurological
      disorders. Notably, a total of 165 cases of bovine encephalomyelitis were
      reported in 2011 and the isolated viruses from affected animals shared high
      genetic identities with a South Korean isolate that was associated with a large
      outbreak in 2010, suggesting some epidemiological linkage between these
      epizootics. Epizootics of genogroup II were observed in 2008 and 2010, but bovine
      post-natal encephalomyelitis cases rarely occurred. Our findings suggest that the
      frequent incursion of genogroup I isolates has increased the frequency of post
      natal encephalomyelitis cases in Japan in recent years. Infection by genogroup I
      virus was also identified in piglets with neurological disorders or congenital
      malformations in 2011 and 2013. The aetiological role of AKAV in pigs should be
      elucidated in the future.

PMID- 29193772
TI  - Efficacy of nivolumab in a patient with systemic refractory ALK+ anaplastic large
      cell lymphoma.

PMID- 29193774
TI  - Optical effects on the surrounding structure during quantitative analysis using
      indocyanine green videoangiography: A phantom vessel study.
AB  - Various reports have been published regarding quantitative evaluations of
      intraoperative fluorescent intensity studies using indocyanine green (ICG) with
      videoangiography (VAG). The effects of scattering and point-spread functions
      (PSF) on quantitative ICG-VAG evaluations have not been investigated. Clinically,
      when ICG is administered through the peripheral vein, it reaches the tissue intra
      arterially. To achieve more reliable intraoperative quantitative intensity
      evaluations, we examined the impact of high-intensity structures on close areas.
      The study was conducted using a phantom model and surgical fluorescent
      microscope. A region of interest (ROI) was created for the vessel model and
      another ROI was created within 3 cm of that. With an ROI of 6.8 mm in the vessel
      phantom model, 10% intensity was confirmed, even though there was no fluorescent
      structure. Intensity decreased gradually as the ROI moved further from the vessel
      model. Our study results suggest that the presence of a high-intensity structure
      and the size of the ROI may affect quantitative intensity evaluations using ICG
      VAG. Results of linear regression analysis indicate that the relationship of
      intensity (Y) and distance (X) is as follows: Y(real/A) = 29 Exp(-0.062X) + 164.3
      Exp(-1.81X). The optical effect should be considered when performing an
      intraoperative intensity study with a surgical microscope.

PMID- 29193775
TI  - Application of ionic-liquid-magnetized stirring bar liquid-phase microextraction
      coupled with HPLC for the determination of naphthoquinones in Zicao.
AB  - In this study, a green, rapid, and simple method, ionic-liquid-magnetized
      stirring bar liquid-phase microextraction was developed for the determination of
      naphthoquinones, including shikonin and beta,beta'-dimethylacrylshikonin, in
      Zicao. This method permits active magnetic stirring, extraction, and pre
      enrichment in a single device simultaneously, so the extract is conveniently
      collected. The analytes were extracted from the sample to ionic liquid-magnetized
      stirring bar, then the analyte-adsorbed magnetized stirring bar can be readily
      isolated from the sample solution by a magnet. The key experimental parameters
      were investigated and optimized, including the type and volume of ionic liquid,
      extraction time, salt concentration, stirring speed, and pH. The recoveries were
      in the range of 89.47-102.38%, and good reproducibilities were obtained with
      relative standard deviation below 5.36%. Compared with the conventional
      extraction methods, the proposed method is quicker and more effective.

PMID- 29193776
TI  - Bayesian statistical approaches to evaluating cognitive models.
AB  - Cognitive models aim to explain complex human behavior in terms of hypothesized
      mechanisms of the mind. These mechanisms can be formalized in terms of
      mathematical structures containing parameters that are theoretically meaningful.
      For example, in the case of perceptual decision making, model parameters might
      correspond to theoretical constructs like response bias, evidence quality,
      response caution, and the like. Formal cognitive models go beyond verbal models
      in that cognitive mechanisms are instantiated in terms of mathematics and they go
      beyond statistical models in that cognitive model parameters are psychologically
      interpretable. We explore three key elements used to formally evaluate cognitive
      models: parameter estimation, model prediction, and model selection. We compare
      and contrast traditional approaches with Bayesian statistical approaches to
      performing each of these three elements. Traditional approaches rely on an array
      of seemingly ad hoc techniques, whereas Bayesian statistical approaches rely on a
      single, principled, internally consistent system. We illustrate the Bayesian
      statistical approach to evaluating cognitive models using a running example of
      the Linear Ballistic Accumulator model of decision making (Brown SD, Heathcote A.
      The simplest complete model of choice response time: linear ballistic
      accumulation. Cogn Psychol 2008, 57:153-178). WIREs Cogn Sci 2018, 9:e1458. doi:
      10.1002/wcs.1458 This article is categorized under: Neuroscience > Computation
      Psychology > Reasoning and Decision Making Psychology > Theory and Methods.

PMID- 29193773
TI  - Post-genomic behavioral genetics: From revolution to routine.
AB  - : What was once expensive and revolutionary-full-genome sequence-is now
      affordable and routine. Costs will continue to drop, opening up new frontiers in
      behavioral genetics. This shift in costs from the genome to the phenome is most
      notable in large clinical studies of behavior and associated diseases in cohorts
      that exceed hundreds of thousands of subjects. Examples include the Women's
      Health Initiative (www.whi.org), the Million Veterans Program (www. RESEARCH:
      va.gov/MVP), the 100 000 Genomes Project (genomicsengland.co.uk) and commercial
      efforts such as those by deCode (www.decode.com) and 23andme (www.23andme.com).
      The same transition is happening in experimental neuro- and behavioral genetics,
      and sample sizes of many hundreds of cases are becoming routine
      (www.genenetwork.org, www.mousephenotyping.org). There are two major consequences
      of this new affordability of massive omics datasets: (1) it is now far more
      practical to explore genetic modulation of behavioral differences and the key
      role of gene-by-environment interactions. Researchers are already doing the hard
      part-the quantitative analysis of behavior. Adding the omics component can
      provide powerful links to molecules, cells, circuits and even better treatment.
      (2) There is an acute need to highlight and train behavioral scientists in how
      best to exploit new omics approaches. This review addresses this second issue and
      highlights several new trends and opportunities that will be of interest to
      experts in animal and human behaviors.

PMID- 29193777
TI  - Pretreatment C-reactive protein/albumin ratio is associated with poor survival in
      patients with stage IB-IIA cervical cancer.
AB  - Previous studies have shown that the C-reactive protein/albumin ratio (CAR) is a
      prognostic indicator in multiple types of carcinomas. This study is the first to
      evaluate the prognostic significance of CAR in stage IB-IIA cervical cancer
      patients treated with radical surgery, as well as that of several other
      inflammation-based factors, including the neutrophil-to-lymphocyte ratio (NLR),
      platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI). A
      total of 235 patients were enrolled in this study. The optimal cut-off values of
      CAR and other inflammation-based factors were determined by receiver operating
      characteristic curves. The Kaplan-Meier method and Cox regression model analysis
      were performed to determine the independent predictors of progression-free
      survival (PFS) and overall survival (OS). At a cut-off value of 0.15, patients
      with a high CAR had significantly shorter PFS and OS than those with a lower CAR
      (P < 0.001). A higher CAR was significantly associated with elevated scores of
      NLR and PLR and a decreased PNI (P < 0.001). Univariate analyses showed that
      elevated CAR preoperatively was significantly associated with poor survival; a
      similar trend was also noted for the NLR, PLR, and PNI. Multivariate analyses
      demonstrated that only CAR was an independent indicator for PFS (hazard ratio
      [HR]: 5.164; 95% confidence interval [CI]: 2.495-10.687; P < 0.001) and OS (HR:
      4.729; 95% CI: 2.263-9.882; P < 0.001). In conclusion, preoperative CAR is a
      novel and superior predictor of poor survival in patients with stage IB-IIA
      cervical cancer.

PMID- 29193778
TI  - A substitution mutation in OsPELOTA confers bacterial blight resistance by
      activating the salicylic acid pathway.
AB  - We previously reported a spotted-leaf mutant pelota (originally termed HM47) in
      rice displaying arrested growth and enhanced resistance to multiple races of
      Xanthomonas oryzae pv. oryzae. Here, we report the map-based cloning of the
      causal gene OsPELOTA (originally termed splHM47 ). We identified a single base
      substitution from T to A at position 556 in the coding sequence of OsPELOTA,
      effectively mutating phenylalanine to isoleucine at position 186 in the
      translated protein sequence. Both functional complementation and over-expression
      could rescue the spotted-leaf phenotype. OsPELOTA, a paralogue to eukaryotic
      release factor 1 (eRF1), shows high sequence similarity to Drosophila Pelota and
      also localizes to the endoplasmic reticulum and plasma membrane. OsPELOTA is
      constitutively expressed in roots, leaves, sheaths, stems, and panicles. Elevated
      levels of salicylic acid and decreased level of jasmonate were detected in the
      pelota mutant. RNA-seq analysis confirmed that genes responding to salicylic acid
      were upregulated in the mutant. Our results indicate that the rice PELOTA protein
      is involved in bacterial leaf blight resistance by activating the salicylic acid
      metabolic pathway.

PMID- 29193779
TI  - Insulin Access to Skeletal Muscle is Preserved in Obesity Induced by
      Polyunsaturated Diet.
AB  - OBJECTIVE: Diets high in saturated fat induce obesity and insulin resistance and
      impair insulin access to skeletal muscle, leading to reduced insulin levels at
      the muscle cell surface available to bind insulin receptors and induce glucose
      uptake. In contrast, diets supplemented with polyunsaturated fat improve insulin
      sensitivity (SI) and reduce the risk for type 2 diabetes. It was hypothesized
      that a diet high in polyunsaturated fat would preserve SI and insulin access to
      muscle, as compared with a diet high in saturated fat. METHODS: After 12 weeks of
      control, saturated (LARD), or polyunsaturated (salmon oil [SO]) high-fat diet
      feeding, muscle SI and insulin access to skeletal muscle were measured by using
      lymph, a surrogate of skeletal muscle interstitial fluid. RESULTS: Both high-fat
      diets induced similar weight gain, yet only LARD impaired SI. Hyperinsulinemia in
      the LARD group did not induce an increase in basal interstitial insulin,
      suggesting reduced insulin access to muscle after LARD, but not after SO.
      CONCLUSIONS: A diet high in polyunsaturated fat does not impair insulin access to
      muscle interstitium or induce insulin resistance as observed with a saturated fat
      diet, despite similar weight gain. Future studies should determine whether
      dietary SO supplementation improves impairments in insulin access to skeletal
      muscle.

PMID- 29193780
TI  - Presenting characteristics and prevalence of polypoidal choroidal vasculopathy in
      Scandinavian patients with treatment-naive exudative age-related macular
      degeneration.
AB  - PURPOSE: To study presenting characteristics and prevalence of polypoidal
      choroidal vasculopathy (PCV) in Scandinavian Caucasians with treatment-naive
      exudative age-related macular degeneration (AMD). METHODS: We reviewed all
      patients referred in year 2014 and diagnosed using fundus examination, optical
      coherence tomography, and fluorescein and indocyanine green angiography (ICGA).
      Details of found PCVs and its subtypes (clinical and angiographical) were
      correlated to the baseline best-corrected visual acuity (BCVA). RESULTS: Of 299
      Caucasian patients with a tentative diagnosis of exudative AMD, 18 eyes of 17
      patients (5.7%, CI 95%: 3.5-9.1%) had PCV. Patients with PCV were 75.8 (SD: 7.5)
      years old and 11 (65%) were females. Lesions were predominantly extramacular.
      Most eyes (56%) had subretinal haemorrhage, 39% had the exudative type and one
      (6%) eye had the quiescent type. Larger lesion area and disruption of the foveal
      inner-segment/outer-segment layer correlated with worse baseline BCVA. Polypoidal
      choroidal vasculopathy (PCV) type 1 was present in 50% and PCV type 2 in the
      other 50%. Polypoidal choroidal vasculopathy (PCV) type 1 was associated with a
      worse baseline BCVA and greater lesion size. CONCLUSION: Polypoidal choroidal
      vasculopathy (PCV) is not a rare condition in Danes with exudative AMD and
      presents often extramacular and with haemorrhage. This study underscores the
      importance of ICGA as a part of the diagnostic repertoire in AMD and suggests its
      routine use in Scandinavian populations.

PMID- 29193781
TI  - Impact of tumour motion compensation and delineation methods on FDG PET-based
      dose painting plan quality for NSCLC radiation therapy.
AB  - INTRODUCTION: To quantitatively estimate the impact of different methods for both
      boost volume delineation and respiratory motion compensation of [18F] FDG PET/CT
      images on the fidelity of planned non-uniform 'dose painting' plans to the
      prescribed boost dose distribution. METHODS: Six locally advanced non-small cell
      lung cancer (NSCLC) patients were retrospectively reviewed. To assess the impact
      of respiratory motion, time-averaged (3D AVG), respiratory phase-gated (4D GATED)
      and motion-encompassing (4D MIP) PET images were used. The boost volumes were
      defined using manual contour (MANUAL), fixed threshold (FIXED) and gradient
      search algorithm (GRADIENT). The dose painting prescription of 60 Gy base dose to
      the planning target volume and an integral dose of 14 Gy (total 74 Gy) was
      discretized into seven treatment planning substructures and linearly
      redistributed according to the relative SUV at every voxel in the boost volume.
      Fifty-four dose painting plan combinations were generated and conformity was
      evaluated using quality index VQ0.95-1.05, which represents the sum of planned
      dose voxels within 5% deviation from the prescribed dose. Trends in plan quality
      and magnitude of achievable dose escalation were recorded. RESULTS: Different
      segmentation techniques produced statistically significant variations in maximum
      planned dose (P < 0.02), as well as plan quality between segmentation methods for
      4D GATED and 4D MIP PET images (P < 0.05). No statistically significant
      differences in plan quality and maximum dose were observed between motion
      compensated PET-based plans (P > 0.75). Low variability in plan quality was
      observed for FIXED threshold plans, while MANUAL and GRADIENT plans achieved
      higher dose with lower plan quality indices. CONCLUSIONS: The dose painting plans
      were more sensitive to segmentation of boost volumes than PET motion compensation
      in this study sample. Careful consideration of boost target delineation and
      motion compensation strategies should guide the design of NSCLC dose painting
      trials.

PMID- 29193782
TI  - Clinical and ex vivo laboratory comparison of the self-sealing properties and
      dimensional stability between the femtosecond laser and manual clear corneal
      incisions.
AB  - PURPOSE: To compare the self-sealing features and dimensional stability between
      the femtosecond laser (FL) and manual knife corneal incision. METHODS: For the
      clinical study, 29 consecutive eyes from 29 patients and 28 eyes from 28 patients
      who underwent cataract surgery with FL corneal incision and manual knife
      incision, respectively, were enrolled. Immediately after cataract surgery, the
      self-sealing features of the corneal incisions were evaluated. Scanning electron
      microscopy (SEM) images were obtained. For the experimental study, clear corneal
      incisions with a knife or FL with different energy settings (3, 6 and 9 MUJ) were
      created in fresh porcine eyes, followed by a stress test. The incision width was
      measured before and after the stress test. RESULTS: In the clinical study, the
      knife group had a higher self-sealing score (0.60 +/- 0.49 points) than the FL
      group (0.17 +/- 0.38 points). In the experimental study, the deformation rate in
      the knife incision (5.04 +/- 1.93) was significantly lower than that in the FL
      with any energy. The deformation rate in the 9 MUJ (12.98 +/- 2.76) was
      significantly higher than in the 3 MUJ (8.54 +/- 2.38) and 6 MUJ (8.82 +/- 2.85)
      FL energies. Scanning electron microscopy (SEM) images revealed that the corneal
      stromal surface of the knife incision was smoother than that of the FL. Higher
      energy FL showed more irregular surfaces. CONCLUSION: Higher FL energy tended to
      widen a clear corneal incision when mechanical stress was applied. The
      histological differences at the inner tunnel surface may cause differences in
      wound stability of the corneal incision.

PMID- 29193783
TI  - Blue Native/SDS-PAGE and iTRAQ-Based Chloroplasts Proteomics Analysis of
      Nicotiana tabacum Leaves Infected with M Strain of Cucumber Mosaic Virus Reveals
      Several Proteins Involved in Chlorosis Symptoms.
AB  - Virus infection in plants involves necrosis, chlorosis, and mosaic. The M strain
      of cucumber mosaic virus (M-CMV) has six distinct symptoms: vein clearing,
      mosaic, chlorosis, partial green recovery, complete green recovery, and secondary
      mosaic. Chlorosis indicates the loss of chlorophyll which is highly abundant in
      plant leaves and plays essential roles in photosynthesis. Blue native/SDS-PAGE
      combined with mass spectrum was performed to detect the location of virus, and
      proteomic analysis of chloroplast isolated from virus-infected plants was
      performed to quantify the changes of individual proteins in order to gain a
      global view of the total chloroplast protein dynamics during the virus infection.
      Among the 438 proteins quantified, 33 showed a more than twofold change in
      abundance, of which 22 are involved in the light-dependent reactions and five in
      the Calvin cycle. The dynamic change of these proteins indicates that light
      dependent reactions are down-accumulated, and the Calvin cycle was up-accumulated
      during virus infection. In addition to the proteins involved in photosynthesis,
      tubulin was up-accumulated in virus-infected plant, which might contribute to the
      autophagic process during plant infection. In conclusion, this extensive
      proteomic investigation on intact chloroplasts of virus-infected tobacco leaves
      provided some important novel information on chlorosis mechanisms induced by
      virus infection.

PMID- 29193785
TI  - Contribution of hiatal hernia to asthma in patients with gastroesophageal reflux
      disease.
AB  - BACKGROUND: To determine the correlation between asthma and hiatal hernia (HH) in
      patients with gastroesophageal reflux disease (GERD)-related asthma requiring
      laparoscopic anti-reflux surgery. METHODS: One hundred and thirty-six GERD
      patients with medically refractory asthma with (80 patients) or without HH (56
      patients) were enrolled. Gastroesophageal reflux disease was assessed by
      endoscopy, esophageal manometry, reflux monitoring and symptom questionnaires,
      and treated with laparoscopic Nissen fundoplication (LNF) or LNF with concomitant
      hiatal hernia repair (LNF-HHR). The outcome measures included patients'
      satisfaction and drug independence. RESULTS: The patients with HH had lower
      esophageal sphincters (P = .005) and higher DeMeester scores (P = .014) than
      those without HH. After an average follow-up of 24 months, symptom scores were
      significantly decreased from the preoperative values (P < .05). Compared to LNF,
      LNF-HHR showed a better improvement in both esophageal and asthmatic symptoms (P
      < .0001 and P = .016, respectively). CONCLUSIONS: The patients with GERD with
      asthma have a high prevalence of HH. The presence of HH maybe correlated with
      asthma and severe GERD. Actively treating HH not only improved reflux, but also
      controlled asthma symptoms.

PMID- 29193784
TI  - Expression of CPPED1 in human trophoblasts is associated with timing of term
      birth.
AB  - Understanding of timing of human parturition is incomplete. Therefore, we carried
      out proteomic analyses of full-term placentas from uncomplicated pregnancies to
      identify protein signatures associated with the onset of spontaneous delivery. We
      found quantitative associations of 10 proteins with spontaneous term birth,
      evident either in the basal or in the chorionic plates or in both. Additional 18
      proteins were associated according to the location within placenta indicating
      local variations in protein amounts. Calcineurin-like phosphoesterase domain
      containing 1 (CPPED1), a phosphatase previously suggested dephosphorylating
      AKT1/PKB, was one of the identified proteins. qRT-PCR revealed the mRNA level of
      CPPED1 was higher in elective caesarean deliveries than in spontaneous births,
      while immunohistochemistry showed CPPED1 in cytotrophoblasts,
      syncytiotrophoblasts and extravillous trophoblasts. Noteworthy, phosphorylation
      status of AKT1 did not differ between placentas from elective caesarean and
      spontaneous deliveries. Additionally, analyses of samples from infants indicated
      that single-nucleotide polymorphisms rs11643593 and rs8048866 of CPPED1 were
      associated with duration of term pregnancy. Finally, post-transcriptional
      silencing of CPPED1 in cultured HTR8/SVneo cells by siRNAs affected gene
      expression in pathways associated with inflammation and blood vessel development.
      We postulate that functions regulated by CPPED1 in trophoblasts at choriodecidual
      interphase have a role in the induction of term labour, but it may be independent
      of AKT1.

PMID- 29193787
TI  - Identification of the novel HLA-B*27:04:06 allele in a Chinese bone marrow donor.
AB  - HLA-B*27:04:06 differs from HLA-B*27:04:01 by a single-nucleotide substitution at
      position 396 C > A.

PMID- 29193786
TI  - Preferential atrophy of the central retinal ganglion cells in homonymous
      hemianopia due to acquired retrogeniculate lesions demonstrated using swept
      source optical coherence tomography.

PMID- 29193788
TI  - Efficacy and safety of topical depigmenting agent in healthy human fair skin
      female volunteers: A single-arm study.
AB  - BACKGROUND: Skin hyperpigmentation is the darkening of skin due to the increased
      production of melanin in the body. OBJECTIVES: To evaluate the efficacy and
      safety of a botanical-based Rosa E pigmentation serum in healthy fair skin female
      volunteers with wrinkles, skin tone, and pigmentation. METHODS: This was a single
      arm, open label study conducted in healthy Indian females; 18 subjects aged 30
      55, having fair Caucasian-like skin with at least 2 dark skin pigments with
      facial wrinkles diagnosed by dermatologist were selected. Rosa E pigmentation
      serum was applied twice a day for 84 days. Effect was evaluated by (i)
      instrumental technique (spectrophotometer(r) 2600D), (ii) clinically by
      dermatologist regarding product efficacy (skin tone, antiwrinkle, pigmentation),
      and (iii) volunteers self-evaluation. RESULTS: The L* value of spectrophotometer
      reading represents lightness in the skin pigment. Reduction in the pigment was
      reported from day 14, with significant reductions observed till day 84 compared
      with baseline. Significant (P < .0001) skin pigmentation lightening was seen on
      day 14 (1.11) vastly improving on day 84 (1.94) based on photographic
      assessments. The significant reduction in skin pigment was 76.85%, Felix von
      Luschan skin color score was 30.24% (P < .0001) with a 7.38-fold reduction in
      skin tone and 57% reduction in facial wrinkles at day 84 from baseline.
      CONCLUSIONS: Rosa E pigmentation serum was found safe and effective in
      significant reduction in skin pigments, improvement of skin tone, and antiwrinkle
      properties instrumentally, clinically, and self-evaluation by volunteers. In
      these evaluations, best results were seen the longer the Rosa E was used.

PMID- 29193789
TI  - Temporal changes in retinal vascular parameters associated with successful
      panretinal photocoagulation in proliferative diabetic retinopathy: A prospective
      clinical interventional study.
AB  - PURPOSE: We aimed to investigate changes in retinal vascular geometry over time
      after panretinal photocoagulation (PRP) in patients with proliferative diabetic
      retinopathy (PDR). METHODS: Thirty-seven eyes with PDR were included. Wide-field
      fluorescein angiography (Optomap, Optos PLC., Dunfermline, Scotland, UK) was used
      to diagnose PDR at baseline and to assess activity at follow-up month three and
      six. At each time-point, a trained grader measured retinal vessel geometry on
      optic disc (OD) centred images using semiautomated software (SIVA, Singapore I
      Vessel Assessment, National University of Singapore, Singapore) according to a
      standardized protocol. RESULTS: At baseline, the mean age and duration of
      diabetes were 52.8 and 22.3 years, and 65% were male. Mean HbA1c was 69.9
      mmol/mol, and blood pressure was 155/84 mmHg. Of the 37 eyes with PDR, eight
      (22%) eyes had progression at month three and 13 (35%) progressed over six
      months. Baseline characteristics, including age, sex, duration of diabetes,
      HbA1c, blood pressure, vessel geometric variables and total amount of laser
      energy delivered did not differ by progression status. However, compared to
      patients with progression of PDR, patients with favourable treatment outcome had
      alterations in the retinal arteriolar structures from baseline to month six
      (calibre, 154.3 MUm versus 159.5 MUm, p = 0.04, tortuosity 1.12 versus 1.10, p =
      0.04) and in venular structures from baseline to month three (fractal dimension
      1.490 versus 1.499, p = 0.04, branching coefficient (BC) 1.32 versus 1.37, p =
      0.01). CONCLUSION: In patients with PDR, successful PRP leads to alterations in
      the retinal vascular structure. However, baseline retinal vascular geometry
      characteristics did not predict treatment outcome.

PMID- 29193790
TI  - Airway inflammatory phenotypes: Making sputum cell evaluation more accessible for
      clinical use.

PMID- 29193792
TI  - RPL18aB helps maintain suspensor identity during early embryogenesis.
AB  - During embryogenesis, plants are thought to use a mechanism that allows the
      suspensor to maintain its identity. Here, we reported that RPL18aB is involved in
      this mechanism in Arabidopsis thaliana. The suspensor cells proliferated in
      rpl18aB and formed a multicellular structure rather than undergo programmed cell
      death, as in wild type. Suspensors of rpl18aB expressed the embryo proper marker,
      DRN::GFP, but not the suspensor marker, WOX8::GFP. In addition, auxin accumulated
      throughout the suspensors of rpl18aB proembryos. Suspensor-specific expression of
      RPL18aB could rescue the cell proliferation defects in rpl18aB suspensors. These
      findings supported a role for RPL18aB in maintaining suspensor identity.

PMID- 29193791
TI  - IL-35 recombinant protein reverses inflammatory bowel disease and psoriasis
      through regulation of inflammatory cytokines and immune cells.
AB  - Interleukin-35 (IL-35), a member of the IL-12 family, functions as a new anti
      inflammatory factor involved in arthritis, psoriasis, inflammatory bowel disease
      (IBD) and other immune diseases. Although IL-35 can significantly prevent the
      development of inflammation in many diseases, there have been no early studies
      accounting for the role of IL-35 recombinant protein in IBD and psoriasis. In
      this study, we assessed the therapeutic potential of IL-35 recombinant protein in
      three well-known mouse models: the dextransulfate sodium (DSS)-induced colitis
      mouse model, the keratin14 (K14)-vascular endothelial growth factor A (VEGF-A)
      transgenic (Tg) psoriasis mouse model and the imiquimod (IMQ)-induced psoriasis
      mouse model. Our results indicated that IL-35 recombinant protein can slow down
      the pathologic process in DSS-induced acute colitis mouse model by decreasing the
      infiltrations of macrophages, CD4+ T and CD8+ T cells and by promoting the
      infiltration of Treg cells. Further analysis demonstrated that IL-35 recombinant
      protein may regulate inflammation through promoting the secretion of IL-10 and
      inhibiting the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha
      and IL-17 in acute colitis model. In addition, lower dose of IL-35 recombinant
      protein could achieve long-term treatment effects as TNF-alpha monoclonal
      antibody did in the psoriasis mouse. In summary, the remarkable therapeutic
      effects of IL-35 recombinant protein in acute colitis and psoriasis mouse models
      indicated that IL-35 recombinant protein had a variety of anti-inflammatory
      effects and was expected to become an effective candidate drug for the treatment
      of inflammatory diseases.

PMID- 29193793
TI  - Nanomaterial-Enabled Wearable Sensors for Healthcare.
AB  - Highly sensitive wearable sensors that can be conformably attached to human skin
      or integrated with textiles to monitor the physiological parameters of human body
      or the surrounding environment have garnered tremendous interest. Owing to the
      large surface area and outstanding material properties, nanomaterials are
      promising building blocks for wearable sensors. Recent advances in the
      nanomaterial-enabled wearable sensors including temperature,
      electrophysiological, strain, tactile, electrochemical, and environmental sensors
      are presented in this review. Integration of multiple sensors for multimodal
      sensing and integration with other components into wearable systems are
      summarized. Representative applications of nanomaterial-enabled wearable sensors
      for healthcare, including continuous health monitoring, daily and sports activity
      tracking, and multifunctional electronic skin are highlighted. Finally,
      challenges, opportunities, and future perspectives in the field of nanomaterial
      enabled wearable sensors are discussed.

PMID- 29193794
TI  - Making stillbirths visible: a systematic review of globally reported causes of
      stillbirth.
AB  - BACKGROUND: Stillbirth is a global health problem. The World Health Organization
      (WHO) application of the International Classification of Diseases for perinatal
      mortality (ICD-PM) aims to improve data on stillbirth to enable prevention.
      OBJECTIVES: To identify globally reported causes of stillbirth, classification
      systems, and alignment with the ICD-PM. SEARCH STRATEGY: We searched CINAHL,
      EMBASE, Medline, Global Health, and Pubmed from 2009 to 2016. SELECTION CRITERIA:
      Reports of stillbirth causes in unselective cohorts. DATA COLLECTION AND
      ANALYSIS: Pooled estimates of causes were derived for country representative
      reports. Systems and causes were assessed for alignment with the ICD-PM. Data are
      presented by income setting (low, middle, and high income countries; LIC, MIC,
      HIC). MAIN RESULTS: Eighty-five reports from 50 countries (489 089 stillbirths)
      were included. The most frequent categories were Unexplained, Antepartum
      haemorrhage, and Other (all settings); Infection and Hypoxic peripartum (LIC),
      and Placental (MIC, HIC). Overall report quality was low. Only one classification
      system fully aligned with ICD-PM. All stillbirth causes mapped to ICD-PM. In a
      subset from HIC, mapping obscured major causes. CONCLUSIONS: There is a paucity
      of quality information on causes of stillbirth globally. Improving investigation
      of stillbirths and standardisation of audit and classification is urgently needed
      and should be achievable in all well-resourced settings. Implementation of the
      WHO Perinatal Mortality Audit and Review guide is needed, particularly across
      high burden settings. FUNDING: HR, SH, SHL, and AW were supported by an NHMRC-CRE
      grant (APP1116640). VF was funded by an NHMRC-CDF (APP1123611). TWEETABLE
      ABSTRACT: Urgent need to improve data on causes of stillbirths across all
      settings to meet global targets. PLAIN LANGUAGE SUMMARY: Background and methods
      Nearly three million babies are stillborn every year. These deaths have deep and
      long-lasting effects on parents, healthcare providers, and the society. One of
      the major challenges to preventing stillbirths is the lack of information about
      why they happen. In this study, we collected reports on the causes of stillbirth
      from high-, middle-, and low-income countries to: (1) Understand the causes of
      stillbirth, and (2) Understand how to improve reporting of stillbirths. Findings
      We found 85 reports from 50 different countries. The information available from
      the reports was inconsistent and often of poor quality, so it was hard to get a
      clear picture about what are the causes of stillbirth across the world. Many
      different definitions of stillbirth were used. There was also wide variation in
      what investigations of the mother and baby were undertaken to identify the cause
      of stillbirth. Stillbirths in all income settings (low-, middle-, and high-income
      countries) were most frequently reported as Unexplained, Other, and Haemorrhage
      (bleeding). Unexplained and Other are not helpful in understanding why a baby was
      stillborn. In low-income countries, stillbirths were often attributed to
      Infection and Complications during labour and birth. In middle- and high-income
      countries, stillbirths were often reported as Placental complications.
      Limitations We may have missed some reports as searches were carried out in
      English only. The available reports were of poor quality. Implications Many
      countries, particularly those where the majority of stillbirths occur, do not
      report any information about these deaths. Where there are reports, the quality
      is often poor. It is important to improve the investigation and reporting of
      stillbirth using a standardised system so that policy makers and healthcare
      workers can develop effective stillbirth prevention programs. All stillbirths
      should be investigated and reported in line with the World Health Organization
      standards.

PMID- 29193796
TI  - Visibility of an iron-containing fiducial marker in magnetic resonance imaging
      for high-precision external beam prostate radiotherapy.
AB  - INTRODUCTION: Visualization of fiducial gold markers is critical for registration
      on computed tomography (CT) and magnetic resonance imaging (MRI) for imaging
      guided radiotherapy. Although larger markers provide better visualization on MRI,
      they tend to generate artifacts on CT. MRI is strongly influenced by the presence
      of metals, such as iron, in the body. Here we compared efficacies of a 0.5% iron
      containing gold marker (GM) and a traditional non-iron-containing marker.
      METHODS: Twenty-seven patients underwent CT/MRI fusion-based intensity-modulated
      radiotherapy. Markers were placed by urologists under local anesthesia. Gold
      Anchor (GA; diameter: 0.28 mm; length: 10 mm), an iron-containing marker, was
      placed on the right side of the prostate using a 22-G needle and VISICOIL (VIS;
      diameter: 0.35 mm; length: 10 mm), a non-iron-containing marker, was placed on
      the left side using a 19-G needle. T2*-weighted images MRI sequences were
      obtained. Two radiation oncologists and a radiation technologist evaluated and
      assigned scores for visual quality on a five-point scale (1, poor; 5, best
      visibility). RESULTS: Artifact generation on CT was slightly greater with GA than
      with VIS. The mean marker visualization scores on MRI of all three observers were
      significantly superior for GA than for VIS (3.5 vs 3.2, 3.9 vs 3.2, and 4.0 vs
      2.9). The actual size of the spherical GA was about 2 mm in diameter, but the
      signal void on MRI was approximately 5 mm. CONCLUSION: Although both markers were
      well visualized and can be recommended clinically, the results suggest that GA
      has some subtle advantages for quantitative visualization that could prove useful
      in certain situations of stereotactic body radiotherapy and intensity-modulated
      radiotherapy.

PMID- 29193795
TI  - Lower mean blood glucose during short-term intensive insulin therapy is
      associated with long-term glycemic remission in patients with newly diagnosed
      type 2 diabetes: Evidence-based recommendations for standardization.
AB  - AIMS/INTRODUCTION: Optimal glycemic targets during short-term intensive insulin
      therapy in patients with newly diagnosed type 2 diabetes are not standardized.
      The present study was carried out to determine the optimal glycemic targets
      during therapy by analyzing the impacts of glucose levels on therapeutic
      outcomes. MATERIALS AND METHODS: A total of 95 individuals with newly diagnosed
      type 2 diabetes were enrolled. Short-term intensive insulin therapy was carried
      out using an insulin pump to achieve and maintain glycemic targets (fasting blood
      glucose <=6.0 mmol/L, 2-h postprandial blood glucose <=7.8 mmol/L) for 14 days,
      with daily eight-point capillary blood glucose profiles recorded. Patients were
      followed up for 1 year after discharge. RESULTS: In most participants, the mean
      blood glucose and glycemic excursion parameters during the therapy were
      controlled within the normal range. Mean blood glucose was independently
      associated with amelioration of acute insulin response (r = -0.25, P = 0.015) and
      1-year remission (odds ratio 0.12, 95% confidence interval 0.034-0.426), but
      negatively associated with more level 1 hypoglycemia (r = -0.34, P = 0.001),
      although major hypoglycemia was rare. Among mean blood glucose tertiles, patients
      in the middle (68.7%) and lower (75.0%) tertiles had a higher 1-year remission
      rate compared with the upper tertile (32.3%, both P < 0.001), whereas only the
      middle tertile did not have increased hypoglycemia compared with the upper
      tertile (8.1 +/- 5.4 vs 7.2 +/- 3.9 events/person, P = 0.48). CONCLUSIONS:
      Stricter glycemic control during short-term intensive insulin therapy produced
      more remission despite self-manageable hypoglycemia. Based on glycemic parameters
      in the middle mean tertile, we propose new glycemic targets that are
      approximately 0.4 mmol/L lower than current the targets, as long-term benefit
      outweighs short-term risks.

PMID- 29193798
TI  - HLA-A*30:125 shows a new antigen binding domain created from HLA-A*30:01 and HLA
      A*30:02.
AB  - A new HLA-A allele, A*30:125, was characterized in a Spanish individual.

PMID- 29193797
TI  - The long non-coding RNA PVT1 represses ANGPTL4 transcription through binding with
      EZH2 in trophoblast cell.
AB  - Despite progress in diagnostics and treatment for preeclampsia, it remains the
      foremost cause of maternal and foetal perinatal morbidity and mortality
      worldwide. Over recent years, various lines of evidence have emphasized long non
      coding RNAs (lncRNAs) which function as an innovative regulator of biological
      behaviour, as exemplified by proliferation, apoptosis and metastasis. However,
      the role of lncRNAs has not been well described in preeclampsia. Here, we
      identified a lncRNA, PVT1, whose expression was down-regulated in qRT-PCR
      analyses in severe preeclampsia. The effects of PVT1 on development were studied
      after suppression and overexpression of PVT1 in HTR-8/SVneo and JEG3 cells. PVT1
      knockdown notably inhibited cell proliferation and stimulated cell cycle
      accumulation and apoptosis. Exogenous PVT1 significantly increased cell
      proliferation. Based on analysis of RNAseq data, we found that PVT1 could affect
      the expression of numerous genes, and then investigated the function and
      regulatory mechanism of PVT1 in trophoblast cells. Further mechanistic analyses
      implied that the action of PVT1 is moderately attributable to its repression of
      ANGPTL4 via association with the epigenetic repressor Ezh2. Altogether, our study
      suggests that PVT1 could play an essential role in preeclampsia progression and
      probably acts as a latent therapeutic marker; thus, it might be a useful
      prognostic marker when evaluating new therapies for patients with preeclampsia.

PMID- 29193799
TI  - Preliminary Evaluation of Artemisinin-Cholesterol Conjugates as Potential Drugs
      for the Treatment of Intractable Forms of Malaria and Tuberculosis.
AB  - To evaluate the feasibility of developing drugs that may be active against both
      malaria and tuberculosis (TB) by using in part putative cholesterol transporters
      in the causative pathogens and through enhancement of passive diffusion in
      granulomatous TB, artemisinin-cholesterol conjugates were synthesized by
      connecting the component molecules through various linkers. The compounds were
      screened in vitro against Plasmodium falciparum (Pf) and Mycobacterium
      tuberculosis (Mtb). Antimalarial activities (IC50 ) against Pf drug-sensitive
      NF54, and drug-resistant K1 and W2 strains ranged from 0.03-2.6, 0.03-1.9, and
      0.02-1.7 MUm. Although the compounds are less active than the precursor
      artemisinin derivatives, the cholesterol moiety renders the compounds relatively
      insoluble in the culture medium, and variation in solubilities among the
      different compounds may reflect in the range of efficacies observed. Activities
      against Mtb H37Rv were assessed using a standardized colony-forming unit (CFU)
      assay after 24 h pretreatment of cultures with each of the compounds. Percentage
      inhibition ranged from 3-38 % and 18-52 % at 10 and 80 MUm, respectively. Thus,
      in contrast to the comparator drug artemether, the conjugates display enhanced
      activities. The immediate aims include the preparation of conjugates with
      enhanced aqueous solubilities, assays against malaria and TB in vivo, and for TB,
      assays using an infected macrophage model and assessment of granuloma influx.

PMID- 29193800
TI  - Suppression of circadian secretion of glucagon-like peptide-1 by the saturated
      fatty acid, palmitate.
AB  - AIM: Glucagon-like peptide-1 is an incretin hormone secreted by the intestinal L
      cell with a circadian rhythm that parallels expression of the core clock gene,
      Bmal1. Although feeding rats a high-fat/high-sucrose Western diet impairs
      rhythmic glucagon-like peptide-1 release, the mechanisms underlying this effect
      remain unclear. Therefore, the aim of this study was to determine the pathway(s)
      by which the saturated fat, palmitate, a major component of the Western diet,
      impairs circadian glucagon-like peptide-1 secretion. METHODS: Murine mGLUTag L
      cells were synchronized, and the effects of palmitate pre-treatment on gene
      expression and glucagon-like peptide-1 secretion were determined, in addition to
      metabolite quantification, mitochondrial function analysis and enzyme inhibition
      and activation assays. Glucagon-like peptide-1 secretion was also analysed in
      ileal crypt cultures from control and Bmal1 knockout mice. RESULTS: Pre-treatment
      with palmitate dampened Bmal1 mRNA and protein expression and glucagon-like
      peptide-1 secretion at 8 but not 20 hours after cell synchronization (P < .05
      .001). Glucagon-like peptide-1 release was also impaired in Bmal1 knockout
      cultures as compared to wild-type controls (P < .001). Palmitate pre-treatment
      reduced expression of the Bmal1 downstream target, nicotinamide
      phosphoribosyltransferase, the rate-limiting enzyme in the synthesis of NAD+ .
      This was paralleled by dampening of total NAD+ levels, as well as impaired
      mitochondrial function and ATP production (P < .05-.001). Whereas direct
      inhibition of nicotinamide phosphoribosyltransferase also decreased glucagon-like
      peptide-1 release, activation of this enzyme restored glucagon-like peptide-1
      secretion in the presence of palmitate. CONCLUSION: Palmitate impairs L-cell
      clock function at the peak of Bmal1 gene expression, thereby impairing
      mitochondrial function and ultimately rhythmic glucagon-like peptide-1 secretion.

PMID- 29193801
TI  - A design-by-treatment interaction model for network meta-analysis and meta
      regression with integrated nested Laplace approximations.
AB  - Network meta-analysis (NMA) is gaining popularity for comparing multiple
      treatments in a single analysis. Generalized linear mixed models provide a
      unifying framework for NMA, allow us to analyze datasets with dichotomous,
      continuous or count endpoints, and take into account multiarm trials, potential
      heterogeneity between trials and network inconsistency. To perform inference
      within such NMA models, the use of Bayesian methods is often advocated. The
      standard inference tool is Markov chain Monte Carlo (MCMC), which is
      computationally expensive and requires convergence diagnostics. A deterministic
      approach to do fully Bayesian inference for latent Gaussian models can be
      achieved by integrated nested Laplace approximations (INLA), which is a fast and
      accurate alternative to MCMC. We show how NMA models fit in the class of latent
      Gaussian models and how NMA models are implemented using INLA and demonstrate
      that the estimates obtained by INLA are in close agreement with the ones obtained
      by MCMC. Specifically, we emphasize the design-by-treatment interaction model
      with random inconsistency parameters (also known as the Jackson model). Also, we
      have proposed a network meta-regression model, which is constructed by
      incorporating trial-level covariates to the Jackson model to explain possible
      sources of heterogeneity and/or inconsistency in the network. A publicly
      available R package, nmaINLA, is developed to automate the INLA implementation of
      NMA models, which are considered in this paper. Three applications illustrate the
      use of INLA for a NMA.

PMID- 29193802
TI  - A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting
      Macrophages and Dendritic Cells.
AB  - A MUC1 anticancer vaccine equipped with covalently linked divalent mannose
      ligands was found to improve the antigen uptake and presentation by targeting
      mannose-receptor-positive macrophages and dendritic cells. It induced much
      stronger specific IgG immune responses in mice than the non-mannosylated
      reference vaccine. Mannose coupling also led to increased numbers of macrophages,
      dendritic cells, and CD4+ T cells in the local lymph organs. Comparison of di-
      and tetravalent mannose ligands revealed an increased binding of the tetravalent
      version, suggesting that higher valency improves binding to the mannose receptor.
      The mannose-coupled vaccine and the non-mannosylated reference vaccine induced
      IgG antibodies that exhibited similar binding to human breast tumor cells.

PMID- 29193803
TI  - Investigating the robustness and extraction performance of a matrix-compatible
      solid-phase microextraction coating in human urine and its application to assess
      2-6-ring polycyclic aromatic hydrocarbons using GC-MS/MS.
AB  - In this work, a polydimethylsiloxane/divinylbenzene fiber overcoated with a layer
      of polydimethylsiloxane was evaluated as analytical sampling tool for the first
      time in human urine. Urinary polycyclic aromatic hydrocarbons with 2-6 aromatic
      rings were considered as target compounds. The analyte uptake in kinetic and
      thermodynamic regime was evaluated and compared to the performances of
      polydimethylsiloxane/divinylbenzene and polydimethylsiloxane fibers. The
      assessment of the robustness and endurance of the overcoated fiber was carried
      out by direct immersion solid-phase microextraction in undiluted urine performing
      up to 120 consecutive extractions. The overcoated fiber was then used to develop
      a fast and easy direct immersion solid-phase microextraction with gas
      chromatography and triple quadrupole mass spectrometry protocol for the
      quantification of the target polycyclic aromatic hydrocarbons. The attained
      values of accuracy and precision were 75-114% and 2-19%, respectively, while the
      limits of quantification ranged between 0.05 and 1 ng/L. The proposed protocol
      was applied to the screening of urine samples collected from smoking and
      nonsmoking volunteers. The successful results obtained by using the overcoated
      fiber create not only new alternatives for polycyclic aromatic hydrocarbon
      exposure assessment but also new perspectives for the application of direct
      immersion solid-phase microextraction to the analysis of bioclinical matrixes.

PMID- 29193804
TI  - Primary cutaneous aspergillosis, mimicking malignancy, a rare presentation in an
      immunocompetent patient.
AB  - Aspergillus species are ubiquitous opportunistic molds that cause both allergic
      and invasive syndromes. A 65-year-old female, farmer by occupation, presented
      with left upper limb and trunk swelling for one year, associated with pain,
      tightening of skin, and vesicles with watery discharge. Local examination showed
      a diffuse swelling extending from left arm to forearm and lateral chest wall
      associated with edema, induration, and raised temperature. The swelling was firm
      to hard with superficial skin ulcers and black eschar. Hematological
      investigations of the patient showed raised total WBC count and peripheral blood
      eosinophilia. Patient had no history suggesting immunosuppression. Clinico
      radiological impression was left breast carcinoma with secondary skin
      involvement. fine-needle aspiration cytology (FNAC) from the swelling showed
      inflammatory cells, necrosis, epitheloid cell granulomas, and giant cells along
      with branching hyphae of variable thickness, confirmed on Gomori Methenamine
      Silver stain as fungal hyphae. Culture was advised which identified the species
      as Aspergillius fumigatus. Primary cutaneous infection by A. fumigatus in an
      immunocompetent patient is unheard of. FNAC has an important role in resolving
      diagnostic dilemma in primary cutaneous aspergillosis, which may mimic malignancy
      as in our case.

PMID- 29193805
TI  - Separation and determination of polyurethane amine catalysts in polyether polyols
      by using UHPLC-Q-TOF-MS on a reversed-phase/cation-exchange mixed-mode column.
AB  - A simple, selective, and accurate ultra-high performance liquid chromatography
      coupled with quadrupole time-of-flight mass spectrometry method was established
      and validated for the efficient separation and quantification of polyurethane
      amine catalysts in polyether polyols. Amine catalysts were primarily separated in
      polyether polyol-based sample by solid-phase extraction, and further baseline
      separated on a reversed-phase/cation-exchange mixed-mode column (SiELC PrimesepTM
      200) using 0.1% trifluoroacetic acid/acetonitrile as a mobile phase in gradient
      elution mode at a flow rate of 0.2 mL/min. High-resolution quadrupole time-of
      flight mass spectrometry analysis in electrospray ionization positive mode
      allowed the identification as N,N'-bis[3-(dimethylamino)propyl]urea, N-[2-(2
      dimethylaminoethoxy)ethyl]-N-methyl-1,3-propanediamine, and N,N,N',N'
      tetramethyldipropylenetriamine. The method was validated and presented good
      linearity for all the analytes in blank matrices within the concentration range
      of 0.20-5.0 or 0.1-2.0 MUg/mL with the correlation coefficients (R2 ) ranging
      from 0.986 to 0.997. Method recovery ranged within 81-105% at all three levels
      (80, 100, and 120% of the original amount) with relative standard deviations of
      1.0-6.2%. The limits of detection were in the range of 0.007-0.051 MUg/mL. Good
      precision was obtained with relative standard deviation below 3.2 and 0.72% for
      peak area and retention time of three amines, respectively.

PMID- 29193806
TI  - Inhibition of larval growth and adult fecundity in Asian long-horned beetle
      (Anoplophora glabripennis) exposed to azadirachtins under quarantine laboratory
      conditions.
AB  - BACKGROUND: The Asian long-horned beetle [ALB; Anoplophora glabripennis
      (Motschulsky)] is an invasive, wood-boring insect posing significant economic and
      ecological threats to the deciduous forests of North America. An efficacious and
      environmentally acceptable chemical control technique is a requirement of a
      comprehensive, integrated response strategy. RESULTS: Results of this study
      demonstrate statistically significant, concentration-dependent effects of
      azadirachtins, a family of natural compounds derived from the neem tree, on both
      ALB larval and adult life stages. Growth inhibitory effects on ALB larvae were
      greatest on early life stages. Significant effects on adults included inhibition
      of female feeding, oviposition effort and fecundity for adults exposed to
      azadirachtins via maturation feeding on systemically loaded twigs. CONCLUSION:
      These quarantine laboratory experiments verify multi-mechanistic, deleterious
      effects on both larval and adult life stages of ALB, an exotic, invasive insect
      pest of critical importance in North America. Field efficacy studies are required
      to further understand dose acquisition by larval and adult ALB life stages
      following systemic injections to host trees under semi-operational use scenarios.
      Such studies could also be used to test postulates regarding optimal deployment
      strategies to meet objectives such as slowing the spread of this pest and
      protection of high-value deciduous forest resources. (c) 2017 Her Majesty the
      Queen in Right of Canada Pest Management Science (c) 2017 Society of Chemical
      Industry.

PMID- 29193807
TI  - Thermal plasticity potentially mediates the interaction between host Chilo
      partellus Swinhoe (Lepidoptera: Crambidae) and endoparasitoid Cotesia flavipes
      Cameron (Hymenoptera: Braconidae) in rapidly changing environments.
AB  - BACKGROUND: Increasing climatic average temperatures and variability elicit
      various insect physiological responses that affect fitness and survival and may
      influence subsequent trophic interactions in agroecosystems. In this background,
      we investigated short- and long-term plastic responses to temperature of the
      laboratory-reared stemborer Chilo partellus and its larval endoparasitoid Cotesia
      flavipes. RESULTS: Rapid cold- and heat-hardening effects in C. partellus larvae,
      pupae and adults and C. flavipes adults were highly significant (P < 0.001). High
      temperature acclimation improved critical thermal limits and heat knockdown time
      in C. partellus larvae and C. flavipes adults, respectively. Low-temperature
      acclimation enhanced the supercooling point in C. flavipes and the chill coma
      recovery time in both C. partellus larvae and C. flavipes adults. CONCLUSION: The
      results of this study suggest that thermal plasticity may enhance the survival of
      these two species when they are subjected to lethal low and high temperatures.
      However, C. partellus appeared to be more plastic than C. flavipes. These results
      have three major implications: (1) C. partellus may inhabit slightly warmer
      environments than C. flavipes, suggesting a potential mismatch in biogeography;
      (2) host-parasitoid relationships are complex and are probably trait dependent,
      and (3) host-parasitoid differential thermal plastic responses may offset
      biocontrol efficacy. These results may help inform biocontrol decision making
      under conditions of global change. (c) 2017 Society of Chemical Industry.

PMID- 29193808
TI  - Molecular epidemiological characterization of Brucella isolates from sheep and
      yaks in northwest China.
AB  - Animal brucellosis is a re-emerging disease in China with high prevalence in the
      northwest region. A total of 66 isolates of Brucella were recovered from sheep
      and yaks in the Inner Mongolia, Xinjiang, Qinghai and Gansu provinces of
      northwest China in 2015 and 2016. Using classical biotyping and the Brucella AMOS
      PCR assay, all isolates were identified as Brucella melitensis biovar 3 (n = 58),
      B. melitensis biovar 1 (n = 1), Brucella abortus (n = 5), or Brucella suis biovar
      3 (n = 2), and B. melitensis biovar 3 was found to be mainly responsible for
      sheep brucellosis in northwest China. Multilocus variable-number tandem-repeat
      analysis (MLVA) was used to identify the epidemiological relationships among the
      isolates and to assess their genetic diversity. Multilocus variable-number tandem
      repeat analysis-16 identified 46 genotypes in these populations, including 37
      unique and nine shared genotypes. Multilocus variable-number tandem-repeat
      analysis-11 showed that 71% of the isolates (47 of 66) were genotype 116 (1-5-3
      13-2-2-3-2-4-41-8), a characteristic subgroup of the East Mediterranean group,
      showing that isolates from different geographical areas exhibit similar
      epidemiological characteristics in different regions and may be epidemiologically
      linked. Multilocus variable-number tandem-repeat analysis-11 also revealed that
      an isolate from Inner Mongolia had a novel genotype, 369 (1-5-3-13-2-2-3-2-7-41
      8). Multilocus variable-number tandem-repeat analysis-16 genotyping of northwest
      China Brucella isolates allows a better understanding of the epidemiology of
      animal brucellosis in this region. This study is the first analysis of B.
      melitensis in Gansu province, and the results confirmed that in this province,
      isolates of this species are disorderly and unsystematic.

PMID- 29193809
TI  - Enhanced headspace single drop microextraction method using deep eutectic solvent
      based magnetic bucky gels: Application to the determination of volatile aromatic
      hydrocarbons in water and urine samples.
AB  - A facile headspace single drop microextraction method was developed using deep
      eutectic solvent-based magnetic bucky gel as the extraction solvent for the first
      time. The hydrophobic magnetic bucky gel was formed by combining choline
      chloride/chlorophenol deep eutectic solvent and magnetic multiwalled carbon
      nanotube nanocomposite. Magnetic susceptibility, high viscosity, high sorbing
      ability, and tunable extractability of organic analytes are the desirable
      advantages of the prepared gel. Using a rod magnet as a suspensor in combination
      with the magnetic susceptibility of the prepared gel resulted in a highly stable
      droplet. This stable droplet eliminated the possibility of drop dislodgement. The
      prepared droplet made it possible to complete the extraction process in high
      temperatures and elevated agitation rates. Furthermore, using larger micro
      droplet volumes without any operational problems became possible. These facts
      resulted in shorter sample preparation time, higher sensitivity of the method,
      and lower detection limits. Under the optimized conditions, an enrichment factor
      of 520-587, limit of detection of 0.05-0.90 ng/mL, and linearity range of 0.2
      2000 ng/mL (coefficient of determination = 0.9982-0.9995) were obtained. Relative
      standard deviations were < 10%. This method was successfully coupled with gas
      chromatography and used for the determination of benzene, toluene, ethylbenzene,
      and xylene isomers as harmful volatile organic compounds in water and urine
      samples.

PMID- 29193811
TI  - Volume 69 Table of Contents.

PMID- 29193812
TI  - Exploring literature-based definitions of hypotony following glaucoma filtration
      surgery and the impact on clinical outcomes.
AB  - PURPOSE: To highlight the variations in published definitions of hypotony and
      their impact on reported clinical outcomes. To propose a revised definition,
      focusing on clinically significant hypotony (CH). METHODS: Literature review of
      hypotony definitions published between January 2010 and December 2015 was carried
      out. Numerical definitions for hypotony, its onset, duration and associated
      clinical signs were recorded. Each definition was applied to surgical outcomes
      data collected prospectively from a cohort of 300 glaucoma patients treated at a
      single centre. The sensitivity and specificity of each definition in identifying
      CH [defined as low intraocular pressure (IOP) with signs of maculopathy hypotony
      and choroidal detachment] were calculated. RESULTS: A total of 128 eligible
      papers were identified, and 14 different definitions for hypotony were extracted.
      In 53 (41.4%), hypotony was not defined. In the remaining 75 (58.6%), the
      numerical definitions varied between 4 and 8 mmHg, and of these, 24 (32%)
      included the onset and duration of hypotony as part of the definition. Definition
      dependent hypotony rates within the cohort varied between 1% and 59.3%. No
      statistical differences were found between the groups based on corneal thickness
      or axial length. Clinically significant hypotony (CH) was identified in 37
      (12.3%), with large differences in the sensitivity and specificity among
      published definition. CONCLUSION: Variations in defining postoperative hypotony
      can have a large impact on the reported success and failure rates among studies.
      There is a need for a more robust universal definition, focusing on clinically
      important signs, to allow better comparison between different treatment
      modalities.

PMID- 29193813
TI  - A case report of brown tumor in a patient with chronic renal failure and renal
      cell carcinoma.
AB  - We report a case of a 72 year old male with hyperparathyroidism secondary to end
      stage diabetic renal disease and coexisting bilateral chromophobe renal cell
      carcinomas. The patient presented with back and groin pain, right pelvic
      hemorrhage, and multiple lytic bone lesions concerning for metastatic renal cell
      carcinoma. Fine needle aspiration cytology demonstrated benign appearing
      osteoclasts and spindled cells. A concurrent core biopsy showed foci of spindled
      cell proliferation populated by osteoclast-like giant cells with stromal
      hemorrhage without evidence of metastatic carcinoma. The cytologic and histologic
      findings, in correlation with the clinical history, radiographic features,
      markedly increased parathyroid hormone levels and other serologic studies, were
      diagnostic of the reactive lesion seen in brown tumor of hyperparathyroidism
      secondary to chronic renal failure.

PMID- 29193814
TI  - Hospital admissions for lower respiratory tract infections in children born
      moderately/late preterm.
AB  - OBJECTIVE: To evaluate the frequency and predictors of hospital admissions for
      lower respiratory tract infections (LRTIs) in moderately preterm (MP, 32+0 to
      33+6 weeks) and late preterm (LP, 34+0 to 36+6 weeks) infants compared to term (T
      >=37 weeks) and very preterm (VP, <32+0 weeks) infants. STUDY DESIGN: This
      national register-based study covered all infants born in Finland in 1991-2008.
      Data on 1 018 256 infants were analyzed in four gestational age-based groups: VP
      (n = 6329), MP (n = 6796), LP (n = 39 928), and T (n = 965 203) groups. Data on
      hospital admissions due to bronchiolitis/bronchitis and pneumonia were collected
      up to the age of 7 years. RESULTS: Hospital admissions for LRTIs were more common
      in the MP and LP groups than in the T group but less frequent than in the VP
      group: bronchiolitis/bronchitis (VP 24.4%, MP 13.9%, LP 9.5%, and T 5.6%) and
      pneumonia (VP 8.8%, MP 4.5%, LP 3.3%, and T 2.4%). Compared to the term group, MP
      and LP birth predicted bronchiolitis/bronchitis (MP OR 1.89; 95%CI 1.75-2.03, LP
      1.51; 1.45-1.56) and pneumonia (MP 1.49; 1.32-1.67, LP 1.25; 1.18-1.33)
      admissions. Statistically significant risk factors for LRTIs included maternal
      smoking, cesarean section, male sex, admission to a neonatal unit and ventilator
      therapy. In addition, being first-born, being born SGA and neonatal antibiotic
      therapy were associated with bronchiolitis/bronchitis. CONCLUSIONS: MP and LP
      births, in addition to VP birth, have a significant impact on respiratory
      infectious morbidity and the need of hospital admissions for LRTIs.

PMID- 29193815
TI  - Introduction to special section on using pools to generate Good Laboratory
      Practice tox or other non-clinical material to accelerate development timelines.

PMID- 29193817
TI  - Isolation and purification of food-grade C-phycocyanin from Arthrospira platensis
      and its determination in confectionery by HPLC with diode array detection.
AB  - C-Phycocyanin is the major phycobiliprotein in Arthrospira platensis, also known
      as Spirulina, which is a cyanobacterium used as a dietary supplement because of
      its powerful effects on body and brain. C-phycocyanin is a blue-colored accessory
      photosynthetic pigment with multiple applications in food industry as natural dye
      or additive, and in pharmaceuticals. This study presents a simple protocol for
      the extraction and purification of food-grade C-phycocyanin from Arthrospira
      platensis. The cell lysis of cyanobacterium was performed by sonication combined
      with repeated freezing and thawing cycles. The purification of the crude extract
      of C-phycocyanin was carried out by ammonium sulfate precipitation followed by
      ion exchange chromatography resulting in 2.5 purity. The purity of
      phycocyanobilin chromophore has been tested by UV-visible spectrophotometry by
      monitoring the absorption after each stage of purification. A high-performance
      liquid chromatography method has been developed and validated for the
      determination of food-grade C-phycocyanin. Intra- and interday precision values
      less than 5.6% and recovery greater than 91.2% indicated high precision and
      accuracy of the method for analysis of C-phycocyanin. The method has been applied
      to commercial confectionery of blue color and to the purified protein obtained in
      the first stage of the study.

PMID- 29193816
TI  - Genetic Fine-Mapping and Identification of Candidate Genes and Variants for
      Adiposity Traits in Outbred Rats.
AB  - OBJECTIVE: Obesity is a major risk factor for multiple diseases and is in part
      heritable, yet the majority of causative genetic variants that drive excessive
      adiposity remain unknown. Here, outbred heterogeneous stock (HS) rats were used
      in controlled environmental conditions to fine-map novel genetic modifiers of
      adiposity. METHODS: Body weight and visceral fat pad weights were measured in
      male HS rats that were also genotyped genome-wide. Quantitative trait loci (QTL)
      were identified by genome-wide association of imputed single-nucleotide
      polymorphism (SNP) genotypes using a linear mixed effect model that accounts for
      unequal relatedness between the HS rats. Candidate genes were assessed by protein
      modeling and mediation analysis of expression for coding and noncoding variants,
      respectively. RESULTS: HS rats exhibited large variation in adiposity traits,
      which were highly heritable and correlated with metabolic health. Fine-mapping of
      fat pad weight and body weight revealed three QTL and prioritized five candidate
      genes. Fat pad weight was associated with missense SNPs in Adcy3 and Prlhr and
      altered expression of Krtcap3 and Slc30a3, whereas Grid2 was identified as a
      candidate within the body weight locus. CONCLUSIONS: These data demonstrate the
      power of HS rats for identification of known and novel heritable mediators of
      obesity traits.

PMID- 29193820
TI  - Osteology and Radiological Anatomy of the Thoracic Limbs of Temminck's Ground
      Pangolin (Smutsia temminckii).
AB  - Temminck's ground pangolin is the only pangolin present in South Africa. It is a
      myrmecophagous mammal with a bipedal gait. The thoracic limbs are used to break
      open ant nests, dig for food, and expand previously occupied burrows. This study
      describes the osteology and radiological anatomy of the thoracic limbs of this
      threatened species. Thoracic limbs from four Temminck's ground pangolins, which
      succumbed from electrocution or natural causes, were digitally radiographed in
      situ. The individual bones were then cleaned, described and digitally
      radiographed. The skeleton of the thoracic limbs revealed a similar number and
      arrangement of bones compared to that of domestic carnivores. The bones were
      robust and displayed numerous open epiphyseal lines. The latter provide an
      estimate of sexual maturity and should not be confused with fractures in injured
      ground pangolins. The scapula was broad and triangular-shaped. The humerus
      displayed a massive medial epicondyle. The radius and ulna were similarly sized,
      and displayed a broad radial trochlea and large olecranon tuber, respectively.
      The manus was composed of seven carpal bones, five short metacarpal bones and
      five digits of which the three central digits were the best developed. The
      unguicular process of the distal phalanx was bifid and elongated. The
      osteological characteristics indicate that the thoracic limbs of Temminck's
      ground pangolin are specifically adapted for protraction and retraction, strong
      elbow extension, flexion of the carpus and digits as well as pronation and
      supination of the antebrachium, as opposed to weight-bearing. These functions are
      likewise documented for other scratch-digging species. Anat Rec, 301:624-635,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29193819
TI  - Efficacy and Safety of Selexipag in Adults With Raynaud's Phenomenon Secondary to
      Systemic Sclerosis: A Randomized, Placebo-Controlled, Phase II Study.
AB  - OBJECTIVE: To determine the effect of selexipag, an oral, selective IP
      prostacyclin receptor agonist, on the frequency of attacks of Raynaud's
      phenomenon (RP) in patients with systemic sclerosis (SSc). METHODS: Patients with
      SSc-related RP were randomized 1:1 to placebo (n = 38) or selexipag (n = 36) in
      individualized doses (maximum of 1,600 MUg twice daily) during a 3-week titration
      period. The primary end point was the weekly average number of RP attacks during
      the study maintenance period, analyzed using a Bayesian approach with a negative
      binomial model adjusted for baseline number of RP attacks. Other outcome measures
      included Raynaud's Condition Score (RCS), RP attack duration, and treatment
      emergent adverse events (AEs). RESULTS: Baseline characteristics were comparable
      between treatment groups. For 83.3% of patients, the individualized maintenance
      dosage of selexipag was <=800 MUg twice daily. No significant difference was
      observed between placebo and selexipag in weekly average number of electronic
      diary (eDiary)-recorded RP attacks during the maintenance period (14.2 attacks
      during the maintenance period and 21.5 attacks during the baseline week in the
      placebo group [n = 32] versus 18.0 attacks during the maintenance period and 22.4
      attacks during the baseline week in the selexipag group [n = 27]; adjusted mean
      treatment difference of 3.4 in favor of placebo). No significant treatment effect
      was observed on RCS or RP attack duration. In the double-blind period, 86.8% of
      placebo-treated patients and 100% of selexipag-treated patients reported >=1 AE;
      55.3% and 91.7%, respectively, reported >=1 prostacyclin-associated AE.
      CONCLUSION: Treatment with selexipag did not reduce the number of RP attacks
      compared with placebo. The safety profile of selexipag was similar to that
      previously reported. This study provides important information about the
      feasibility of eDiary reporting of RP attacks in clinical trials.

PMID- 29193821
TI  - Plastic compressed collagen transplantation - a new option for corneal surface
      reconstruction?

PMID- 29193822
TI  - Evaluating refraction and visual acuity with the Nidek autorefractometer AR-360A
      in a randomized population-based screening study.
AB  - PURPOSE: The evaluation of visual acuity (VA) and refraction in the Northern
      Finland Birth Cohort Eye study was performed using the Nidek AR-360A
      autorefractometer. The accuracy of the method for this population-based screening
      study was assessed. METHODS: Measurements of the refractive error were obtained
      from the right eyes of 1238 subjects (mean age 47), first objectively with the AR
      360A and then subjectively by an optometrist. Agreement with the subjective
      refraction was calculated for sphere, cylinder, mean spherical equivalent (MSE),
      cylindrical vectors J45 and J0 and presbyopic correction (add). Visual acuity
      (VA) was measured using an ETDRS chart and the autorefractometer. RESULTS: The
      refractive error measured with the AR-360A was higher than the subjective
      refraction performed by the optometrist for sphere (0.007 D +/- 0.24 D p = 0.30)
      and also for cylinder (-0.16 D +/- 0.20 D p < 0.0005). The bias between the
      measurements of MSE, J45 and J0 was low: -0.07 D +/- 0.22 D (p = 0.002), 0.01 D
      +/- 0.43 D (p = 0.25) and -0.01 D +/- 0.42 D (p = 0.43), respectively. The amount
      of add measured by the autorefractometer was higher than the subjective 0.35 D +/
      0.29 D (p < 0.0005). There was a statistically significant correlation between
      VA (p < 0.0005) and the difference between the subjective and objective
      refraction. In 99.2% of the measurements, visual values were within one decimal
      line of each other. CONCLUSION: The Nidek AR-360A autorefractometer is an
      accurate tool for determining the refraction and VA in a clinical screening
      trial.

PMID- 29193823
TI  - Striated Perineal Muscles: Location of Somatic and Autonomic Neurons Projecting
      to the Male Pig Ischiocavernous Muscle. Neurochemical Features of the Sympathetic
      Subset.
AB  - The location, number and size of the central and peripheral neurons innervating
      the ischiocavernous muscle (ICM) were studied in male pigs by means of Fast Blue
      (FB) retrograde neuronal tracing. Moreover the immunohistochemical properties of
      the sympathetic ganglia were investigated combining the double immunolabeling
      method. After injection of FB into the left ICM, a mean number of 245.3 +/- 134.9
      labeled neurons were found in the ipsilateral ventral horn of the S1-S3 segments
      of the spinal cord (SC), 129.7 +/- 45.5 in the L6-S3 ipsilateral and S2-S3
      contralateral spinal ganglia (SGs), 2279.3 +/- 622.1 in the ipsilateral L2-S2 and
      contralateral L5-S2 sympathetic trunk ganglia (STGs), 541.7 +/- 158 in the
      bilateral caudal mesenteric ganglia (CMGs), and 78.3 +/- 35.8 in the microganglia
      of the pelvic plexus (PGs). The mean area of the ICM projecting neurons was 1217
      +/- 69.7 MUm2 in the SC, 2737.5 +/- 176.5 MUm2 in the SGs, 982.8 +/- 36.8 MUm2 in
      the STGs, 865.9 +/- 39.14 MUm2 in the CMGs and 426.2 +/- 24.72 MUm2 in the PGs.
      The FB positive neurons of autonomic ganglia contained Dopamine beta hydroxylase,
      vesicular acetylcholine transporter, neuronal nitric oxyde sinthase, calcitonine
      gene related peptide, leu-enkephaline, neuropeptide Y, substance P, vasoactive
      intestinal polypeptide, and somatostatine often colocalized with tyrosine
      hydroxylase. The particular localization of the motor somatic nucleus, the
      abundant autonomic innervation and the qualitatively different content of ICM
      projecting sympathetic neurons suggest a complex regulation of this striated
      muscle involved in involuntary functions, such as the erection, ejaculation,
      micturition and defecation. Anat Rec, 301:837-848, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29193824
TI  - Interactions between protein molecules and the virus removal membrane surface:
      Effects of immunoglobulin G adsorption and conformational changes on filter
      performance.
AB  - Membrane fouling commonly occurs in all filter types during virus filtration in
      protein-based biopharmaceutical manufacturing. Mechanisms of decline in virus
      filter performance due to membrane fouling were investigated using a cellulose
      based virus filter as a model membrane. Filter performance was critically
      dependent on solution conditions; specifically, ionic strength. To understand the
      interaction between immunoglobulin G (IgG) and cellulose, sensors coated with
      cellulose were fabricated for surface plasmon resonance and quartz crystal
      microbalance with energy dissipation measurements. The primary cause of flux
      decline appeared to be irreversible IgG adsorption on the surface of the virus
      filter membrane. In particular, post-adsorption conformational changes in the IgG
      molecules promoted further irreversible IgG adsorption, a finding that could not
      be adequately explained by DLVO theory. Analyses of adsorption and desorption and
      conformational changes in IgG molecules on cellulose surfaces mimicking cellulose
      based virus removal membranes provide an effective approach for identifying ways
      of optimizing solution conditions to maximize virus filter performance. (c) 2017
      American Institute of Chemical Engineers Biotechnol. Prog., 34:379-386, 2018.

PMID- 29193825
TI  - Quality of Life and Depression Among Mexican Americans on Hemodialysis: A
      Preliminary Report.
AB  - Health-related quality of life (QOL) and depression burden of Mexican Americans
      with end-stage renal disease (ESRD) are not known. This observational cross
      sectional study assessed QOL and depression and examined their inter-relatedness
      in Mexican Americans with type 2 diabetes and ESRD on maintenance hemodialysis
      (HD) treatment. Prevalent Mexican Americans on HD (N = 40) completed the Kidney
      Disease Quality of Life-Short Form (KDQOL-SF) and the Beck Depression Inventory
      II. The overall median scores for the mental component summary and the physical
      component summary scales in the KDQOL-SF were 40.9 and 34.0, respectively. The
      prevalence of severe depression was 40%. The most significant differences between
      depressed and non-depressed groups were symptom/problem list, cognitive function,
      and emotional well- being (P < 0.0001 for all). Mexican Americans with depression
      endure a more dismal QOL compared to non-depressed peers. Significant negative
      correlations between depression and several QOL scales underscore plausible
      interactions between the two conditions which warrants further evaluation.

PMID- 29193826
TI  - Validation of eye-tracking measures of social attention as a potential biomarker
      for autism clinical trials.
AB  - : Social communication impairments are a core feature of autism spectrum disorder
      (ASD), and this class of symptoms is a target for treatments for the disorder.
      Measures of social attention, assessed via eye-gaze tracking (EGT), have been
      proposed as an early efficacy biomarker for clinical trials targeting social
      communication skills. EGT measures have been shown to differentiate children with
      ASD from typical children; however, there is less known about their relationships
      with social communication outcome measures that are typically used in ASD
      clinical trials. In the present study, an EGT task involving viewing a videotape
      of an actor making bids for a child's attention was evaluated in 25 children with
      ASD aged 24-72 months. Children's attention to the actor during the dyadic bid
      condition measured via EGT was found to be strongly associated with five well
      validated caregiver-reported outcome measures that are commonly used to assess
      social communication in clinical trials. These results highlight the convergent
      validity of EGT measures of social attention in relation to caregiver-reported
      clinical measures. EGT holds promise as a non-invasive, quantitative, and
      objective biomarker that is associated with social communication abilities in
      children with ASD. Autism Res 2018, 11: 166-174. (c) 2017 International Society
      for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Eye-gaze tracking
      (EGT), an automated tool that tracks eye-gaze patterns, might help measure
      outcomes in clinical trials investigating interventions to treat autism spectrum
      disorders. In this study, an EGT task was evaluated in children with ASD, who
      watched a video with an actor talking directly to them. Patterns of eye-gaze were
      associated with caregiver-reported measures of social communication that are used
      in clinical trials. We show EGT may be a promising objective tool measuring
      outcomes.

PMID- 29193827
TI  - Response to the Letter to the Editor Regarding "Baclofen and Alcohol-Dependent
      Patients: A Real Risk of Severe Self-Poisoning."

PMID- 29193828
TI  - Anxiety and asthma in youth. Is a stress-induced increased cholinergic tone the
      possible link?

PMID- 29193829
TI  - Riboflavin transporter deficiency mimicking mitochondrial myopathy caused by
      complex II deficiency.
AB  - Biallelic likely pathogenic variants in SLC52A2 and SLC52A3 cause riboflavin
      transporter deficiency. It is characterized by muscle weakness, ataxia,
      progressive ponto-bulbar palsy, amyotrophy, and sensorineural hearing loss. Oral
      riboflavin halts disease progression and may reverse symptoms. We report two new
      patients whose clinical and biochemical features were mimicking mitochondrial
      myopathy. Patient 1 is an 8-year-old male with global developmental delay, axial
      and appendicular hypotonia, ataxia, and sensorineural hearing loss. His muscle
      biopsy showed complex II deficiency and ragged red fibers consistent with
      mitochondrial myopathy. Whole exome sequencing revealed a homozygous likely
      pathogenic variant in SLC52A2 (c.917G>A; p.Gly306Glu). Patient 2 is a 14-month
      old boy with global developmental delay, respiratory insufficiency requiring
      ventilator support within the first year of life. His muscle biopsy revealed
      combined complex II + III deficiency and ragged red fibers consistent with
      mitochondrial myopathy. Whole exome sequencing identified a homozygous likely
      pathogenic variant in SCL52A3 (c.1223G>A; p.Gly408Asp). We report two new
      patients with riboflavin transporter deficiency, caused by mutations in two
      different riboflavin transporter genes. Both patients presented with complex II
      deficiency. This treatable neurometabolic disorder can mimic mitochondrial
      myopathy. In patients with complex II deficiency, riboflavin transporter
      deficiency should be included in the differential diagnosis to allow early
      treatment and improve neurodevelopmental outcome.

PMID- 29193831
TI  - Mimicking corneal stroma using keratocyte-loaded photopolymerizable methacrylated
      gelatin hydrogels.
AB  - Cell-laden methacrylated gelatin (GelMA) hydrogels with high (approximately 90%)
      transparency were prepared to mimic the natural form and function of corneal
      stroma. They were synthesized from GelMA with a methacrylation degree of 70% as
      determined by nuclear magnetic resonance. Hydrogels were strong enough to
      withstand handling. Stability studies showed that 87% of the GelMA hydrogels
      remained after 21 days in phosphate buffered saline (PBS). Cell viability in the
      first 2 days was over 90% for the human keratocytes loaded in the gels as
      determined with the live-dead analysis. Cells in the hydrogel elongated and
      connected to each other as observed by confocal laser scanning microscopy (CLSM)
      images and scanning electron microscope analysis after 3 weeks in the culture
      medium and cells were seen to be distributed throughout the hydrogel bulk. Cells
      were found to synthesize collagen Types I and V, decorin, and biglycan
      (representative collagens and proteoglycans of human corneal stroma,
      respectively) showing that keratocytes maintained their functions and preserved
      their phenotypes in the hydrogels. Transparency of cell-loaded and cell-free
      hydrogels after 21 days was found to be over 90% at all time points in the
      visible light range and was comparable to the transparency of the native cornea.
      The corneal stroma equivalent produced in this study that has cells entrapped in
      it leads to a product with homogenous distribution of cells. It was transparent
      at the very beginning and is expected to allow better vision than nontransparent
      substrates. It, therefore, has a significant potential to be used as an
      alternative to the current products used to treat corneal blindness.

PMID- 29193832
TI  - Decision making for independent municipal action.
AB  - Municipalities and cities face myriad challenges with regard to planning;
      decisions that will have long-standing consequences need to be made in the
      context of pressing present concerns, constrained budgets, and uncertainty about
      the future under climate changes. Compounding the challenge may be a lack of
      clear signals from the state and federal leadership on investment priorities.
      This paper contends that existing strategies from decision science can prove
      useful for local governments as they seek actions that are robust despite
      uncertain futures and broadly beneficial across sectors and time horizons. An
      illustrative example of decision making with scenario analysis demonstrates how a
      city can prioritize funding and elevate the baseline functionality of its
      infrastructure and the well-being of its residents, regardless of when and how
      climate hazards occur. Integr Environ Assess Manag 2018;14:194-197. Published
      2017. This article is a US Government work and is in the public domain in the
      USA.

PMID- 29193830
TI  - Effects of cosmetics on the skin microbiome of facial cheeks with different
      hydration levels.
AB  - Basic cosmetics was used by volunteers belonging to high (HHG) and low (LHG)
      hydration groups for 4 weeks, and bacterial communities and biophysical
      parameters in facial skin were analyzed. Hydration level increases and
      transepidermal water loss and roughness decreases were observed in both groups
      after cosmetic use. Bacterial diversity was greater in LHG than HHG, and
      increased after cosmetic use in both groups. Bray-Curtis dissimilarities that
      were higher in LHG than HHG increased in HHG after cosmetic use, whereas they
      decreased in LHG. The phyla Actinobacteria, Proteobacteria, Firmicutes, and
      Bacteroidetes and the genera Propionibacterium, Ralstonia, Burkholderia,
      Staphylococcus, Corynebacterium, Cupriavidus, and Pelomonas were identified as
      common groups and they were not significantly different between LHG and HHG
      except for Propionibacterium that was more abundant in HHG. After cosmetic use,
      Propionibacterium, Staphylococcus, and Corynebacterium decreased, whereas
      Ralstonia, not a core genus, increased, as did KEGG categories of lipid
      metabolism and xenobiotics biodegradation and metabolism, suggesting that
      Ralstonia in skin may have the ability to metabolize cosmetics components.
      Bacterial communities after cosmetic use were different from those in both LHG
      and HHG before the cosmetic use, indicating that bacterial communities in LHG
      were not shifted to resemble those in HHG by cosmetics use.

PMID- 29193833
TI  - Diminished long-term recovery of peak flow rate (PFR) after robotic prostatectomy
      in men with baseline PFR <10 mL/s and incidental association with high-risk
      prostate cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of robot-assisted
      radical prostatectomy (RARP) on uroflowmetry (UF) parameters among men with
      baseline peak flow rates (PFR) <10 mL/s. METHODS: A single-surgeon RARP database
      of 1082 men who underwent prospective UF testing was analyzed. Men filled out
      International Prostate Symptom Score questionnaires and underwent uroflowmetry
      and post-void bladder ultrasound before surgery and at each follow-up visit.
      Patients were divided into 2 groups based on preoperative PFR: those with PFR <10
      mL/s (n = 158) and those with PFR >=10 mL/s (n = 924). Univariate and
      multivariate regression models tested the association of preoperative
      characteristics in predicting postoperative PFR improvement. Within the PFR <10
      mL/s group, preoperative variables were analyzed to predict pathologic outcomes.
      RESULTS: Three months after RARP, men with baseline PFR <10 mL/s had a 3-fold
      improvement in PFR (from mean of 7.0 to 24.2 mL/s), whereas in men with PFR >=10
      mL/s there was a 50% improvement (from mean of 19.7 to 28.9 mL/s; P < .001).
      Improvement in PFR remained stable for >5 years, but mean postoperative PFR was
      20% lower in men with baseline PFR <10 mL/s. Preoperative prostate-specific
      antigen (odds ratio [OR] 0.75; 95% confidence interval [CI] 0.59-0.95) and PFR
      (OR 0.52; 95% CI 0.34-0.80) were independent predictors of the percentage
      improvement in men with baseline PFR <10 mL/s. Preoperative PFR <=7 mL/s was an
      independent predictor of Gleason score >=8 (P = .016), seminal vesicle invasion
      (P = .010), and lymph node invasion (0.029). CONCLUSIONS: After RARP, PFR
      improved significantly, with the improvement persisting over long-term follow-up.
      However, men with baseline PFR <10 mL/s had a 20% lower postoperative PFR over 5
      years, suggesting permanent damage to the bladder and the need for early
      treatment to maintain bladder health. There appears to be an association between
      baseline PFR <=7 mL/s and adverse pathologic features.

PMID- 29193834
TI  - Supplementary search methods were more effective and offered better value than
      bibliographic database searching: A case study from public health and
      environmental enhancement.
AB  - BACKGROUND: We undertook a systematic review to evaluate the health benefits of
      environmental enhancement and conservation activities. We were concerned that a
      conventional process of study identification, focusing on exhaustive searches of
      bibliographic databases as the primary search method, would be ineffective,
      offering limited value. The focus of this study is comparing study identification
      methods. We compare (1) an approach led by searches of bibliographic databases
      with (2) an approach led by supplementary search methods. We retrospectively
      assessed the effectiveness and value of both approaches. METHODS: Effectiveness
      was determined by comparing (1) the total number of studies identified and
      screened and (2) the number of includable studies uniquely identified by each
      approach. Value was determined by comparing included study quality and by using
      qualitative sensitivity analysis to explore the contribution of studies to the
      synthesis. RESULTS: The bibliographic databases approach identified 21 409
      studies to screen and 2 included qualitative studies were uniquely identified.
      Study quality was moderate, and contribution to the synthesis was minimal. The
      supplementary search approach identified 453 studies to screen and 9 included
      studies were uniquely identified. Four quantitative studies were poor quality but
      made a substantive contribution to the synthesis; 5 studies were qualitative: 3
      studies were good quality, one was moderate quality, and 1 study was excluded
      from the synthesis due to poor quality. All 4 included qualitative studies made
      significant contributions to the synthesis. CONCLUSIONS: This case study found
      value in aligning primary methods of study identification to maximise location of
      relevant evidence.

PMID- 29193835
TI  - Incident Spine Surgery in Patients With Ankylosing Spondylitis: A Secondary
      Cohort Analysis of a Nationwide, Population-Based Health Claims Database.
AB  - OBJECTIVE: To evaluate the risk of the need for spine surgery, including cervical
      and lumbar spine surgeries in patients with ankylosing spondylitis (AS), compared
      with those without the disease. METHODS: A secondary data analysis was conducted
      using population-based claims data from the Taiwan National Health Insurance
      Research Database. Adult patients with newly diagnosed AS between January 2000
      and December 2012 were identified based on the International Classification of
      Diseases, Ninth Revision, Clinical Modification code 720.0. A comparison cohort
      was assembled using frequency-matched sex, 10-year age intervals, and index year
      with the AS cohort at a ratio of 5:1. All patients were followed until our study
      outcomes (any spine surgery, cervical spine surgery, and lumbar spine surgery),
      based on surgical codes, had occurred, or until the end of the followup period.
      Incidence rate ratios (IRRs) were calculated using Poisson regression models.
      RESULTS: We identified 3,462 patients with AS and 17,310 patients without AS. All
      3 outcome variables were seen at a significantly higher incidence in the AS
      cohort than in the comparison cohort (IRR 2.34 [95% confidence interval (95% CI)
      1.92-2.87] for any spine surgery, IRR 2.36 [95% CI 1.55-3.59] for cervical spine
      surgery, and IRR 2.33 [95% CI 1.85-2.93] for lumbar spine surgery). Moreover, the
      magnitudes of the IRRs were the largest in the youngest age group (individuals in
      their 20s and 30s). CONCLUSION: Patients with AS, particularly those in their 20s
      and 30s, had a significantly higher risk of needing any spine surgery, cervical
      spine surgery, and lumbar spine surgery, compared with patients without AS.

PMID- 29193836
TI  - Continuous vancomycin in a pediatric cystic fibrosis patient.
AB  - Continuous vancomycin has been previously reported to maximize antimicrobial
      activity while avoiding toxicities associated with dose escalation, but the
      efficacy of this dosing strategy has not been reported. This case report
      describes the successful use of continuous vancomycin, including improvement in
      lung function and avoidance of nephrotoxicity, demonstrated in a pediatric cystic
      fibrosis (CF) patient with MRSA.

PMID- 29193838
TI  - The Role of Nanomechanics in Healthcare.
AB  - Nanomechanics has played a vital role in pushing our capability to detect, probe,
      and manipulate the biological species, such as proteins, cells, and tissues,
      paving way to a deeper knowledge and superior strategies for healthcare.
      Nanomechanical characterization techniques, such as atomic force microscopy,
      nanoindentation, nanotribology, optical tweezers, and other hybrid techniques
      have been utilized to understand the mechanics and kinetics of biospecies.
      Investigation of the mechanics of cells and tissues has provided critical
      information about mechanical characteristics of host body environments. This
      information has been utilized for developing biomimetic materials and structures
      for tissue engineering and artificial implants. This review summarizes
      nanomechanical characterization techniques and their potential applications in
      healthcare research. The principles and examples of label-free detection of
      cancers and myocardial infarction by nanomechanical cantilevers are discussed.
      The vital importance of nanomechanics in regenerative medicine is highlighted
      from the perspective of material selection and design for developing
      biocompatible scaffolds. This review interconnects the advancements made in
      fundamental materials science research and biomedical technology, and therefore
      provides scientific insight that is of common interest to the researchers working
      in different disciplines of healthcare science and technology.

PMID- 29193839
TI  - Implementing noninvasive follicular thyroid neoplasm with papillary-like nuclear
      features may potentially impact the risk of malignancy for thyroid nodules
      categorized as AUS/FLUS and FN/SFN.
AB  - BACKGROUND: Noninvasive encapsulated follicular variant of papillary thyroid
      carcinoma (PTC) has recently been reclassified as noninvasive follicular thyroid
      neoplasm with papillary-like nuclear features (NIFTP). Implementation of the new
      terminology may alter the implied risk of malignancy (ROM) across the six
      categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).
      METHODS: The study cohort consisted of thyroid fine needle aspiration (FNA) cases
      which were assessed between January 2011 and June 2016 and led to surgical
      resections. For each case, patient demographics as well as cytologic and
      corresponding histologic diagnoses were recorded. The surgical specimens
      diagnosed as follicular variant of PTC (FVPTC) were re-reviewed to identify cases
      that met the diagnostic criteria for NIFTP. The ROM with and without exclusion of
      NIFTP from malignant categorization, as well as the relative change in ROM were
      calculated for individual categories of TBSRTC. RESULTS: A total of 908 FNA cases
      with surgical follow-up were retrieved and PTC was identified in 252 (27.8%)
      surgical specimens. Twenty-nine of 252 (11.5%) were initially classified as
      FVPTC, of which 17 (6.7%) were reclassified as NIFTP. The cytologic
      interpretations for the majority of NIFTP cases were atypia of undetermined
      significance/follicular lesion of undetermined significance (AUS/FLUS, n = 8) or
      follicular neoplasm/suspicious for neoplasm/(FN/SFN, n = 4). Excluding NIFTP from
      malignant categorization resulted in a relative decrease in ROM in AUS/FLUS
      (25.8%) and FN/SFN (22.3%) categories. CONCLUSION: Our institutional data
      demonstrates that eliminating NIFTP from malignant categorization may result in a
      reduction of the implied ROM for AUS/FLUS and FN/SFN categories.

PMID- 29193837
TI  - Weight Change During the Early Rheumatoid Arthritis Period and Risk of Subsequent
      Mortality in Women With Rheumatoid Arthritis and Matched Comparators.
AB  - OBJECTIVE: To investigate whether weight change during the early rheumatoid
      arthritis (RA) period is associated with subsequent mortality and to evaluate
      whether there is an RA-specific effect. METHODS: We identified patients with
      incident RA during the Nurses' Health Study (NHS; 1976-2016) and created a
      comparison cohort by matching each RA patient with up to 10 non-RA comparators by
      age and calendar year of the RA diagnosis (index date). To capture weight change
      around the early RA period ("peri-RA/index"), we used weight measurements
      collected 2-4 years before and 2-4 years after the index date. We used Cox
      regression analysis to estimate hazard ratios (HRs) for mortality according to
      peri-RA/index weight change categories, separately in each cohort and in the
      combined cohorts, evaluating for an RA-specific effect. RESULTS: Among 121,701
      women in the NHS, 902 patients with incident RA were identified and matched to
      7,884 non-RA comparators. In the RA cohort, 371 deaths (41.1%) occurred during a
      mean follow-up of 17.0 years after the early RA period, and 2,303 deaths (29.2%)
      occurred in the comparison cohort during a mean follow-up of 18.4 years. Weight
      loss of >30 pounds during the peri-RA period had a hazard ratio (HR) for
      mortality of 2.78 (95% confidence interval [95% CI] 1.58-4.89) compared to stable
      weight; results in the comparison cohort were similar (HR 2.16, 95% CI 1.61
      2.88). A weight gain of >30 pounds had no association with mortality in patients
      with RA (HR 1.45, 95% CI 0.69-3.07) or comparators (HR 1.19, 95% CI 0.89-1.59).
      For mortality, there was no statistically significant interaction between
      RA/comparator status and weight change category (P = 0.68). CONCLUSION: Severe
      weight loss during the early RA period was associated with an increased
      subsequent mortality risk for women with and those without RA. These results
      extend prior observations by including non-RA comparators and finding no
      protective association between weight gain and mortality, providing evidence
      against an RA-specific obesity paradox for mortality.

PMID- 29193840
TI  - Overweight, Obesity, and the Likelihood of Achieving Sustained Remission in Early
      Rheumatoid Arthritis: Results From a Multicenter Prospective Cohort Study.
AB  - OBJECTIVE: Obesity is implicated in rheumatoid arthritis (RA) development,
      severity, outcomes, and treatment response. We estimated the independent effects
      of overweight and obesity on ability to achieve sustained remission (sREM) in the
      3 years following RA diagnosis. METHODS: Data were from the Canadian Early
      Arthritis Cohort, a multicenter observational trial of early RA patients treated
      by rheumatologists using guideline-based care. sREM was defined as Disease
      Activity Score in 28 joints (DAS28) <2.6 for 2 consecutive visits. Patients were
      stratified by body mass index (BMI) as healthy (18.5-24.9 kg/m2 ), overweight (25
      29.9 kg/m2 ), and obese (>=30 kg/m2 ). Cox regression was used to estimate the
      effect of the BMI category on the probability of achieving sREM over the first 3
      years, controlling for age, sex, race, education, RA duration, smoking status,
      comorbidities, baseline DAS28, Health Assessment Questionnaire disability index,
      C-reactive protein level, and initial treatment. RESULTS: Of 982 patients, 315
      (32%) had a healthy BMI, 343 (35%) were overweight, and 324 (33%) were obese; 355
      (36%) achieved sREM within 3 years. Initial treatment did not differ by BMI
      category. Compared to healthy BMI, overweight patients (hazard ratio [HR] 0.75
      [95% confidence interval (95% CI) 0.58-0.98]) and obese patients (HR 0.53 [95% CI
      0.39-0.71]) were significantly less likely to achieve sREM. CONCLUSION: Rates of
      overweight and obesity were high (69%) in this early RA cohort. Overweight
      patients were 25% less likely, and obese patients were 47% less likely, to
      achieve sREM in the first 3 years, despite similar initial disease-modifying
      antirheumatic drug treatment and subsequent biologic use. This is the largest
      study demonstrating the negative impact of excess weight on RA disease activity
      and supports a call to action to better identify and address this risk in RA
      patients.

PMID- 29193841
TI  - Interfacial Engineering of Supported Liquid Membranes by Vapor Cross-Linking for
      Enhanced Separation of Carbon Dioxide.
AB  - Supported liquid membranes (SLMs) based on ionic liquids (ILs) with not only high
      gas permeability and selectivity, but also high stability under high pressure,
      are highly desired for gas separation applications. In this work, permeable and
      selective polyamide network (PN) layers are deposited on the surface of SLMs by
      utilizing the cross-linking reaction of trimesoyl chloride, which was pre
      dispersed in the SLMs, and vapor of amine linkers. The vapor cross-linking method
      makes it easy to control the growth and aggregation of PN layers, owing to the
      significantly reduced reaction rate, and thereby ensuring the good distribution
      of PN layers on the surface of SLMs. With rational choice of amine linkers and
      optimization of vapor cross-linking conditions, the prepared sandwich-like
      PN@SLMs with ILs embedded homogeneously within polymeric matrices displayed much
      improved CO2 permeability and CO2 /N2 selectivity in relation to the pristine
      SLMs. Moreover, those SLMs with ILs impregnated into porous supports physically
      displayed improved stability under high pressure after vapor cross-linking,
      because the PN layers formed on the surface of SLMs help prevent the ILs from
      being squeezed out. This interfacial engineering strategy represents a
      significant advance in the surface modification of SLMs to endow them with
      promising applications in CO2 capture.

PMID- 29193842
TI  - Determining the Risk Factors and Clinical Features Associated With Severe
      Gastrointestinal Dysmotility in Systemic Sclerosis.
AB  - OBJECTIVE: A subset of patients with systemic sclerosis (SSc) develop severe
      gastrointestinal (GI) dysmotility. We sought to determine predictors of severe
      SSc GI dysmotility and to identify distinct features associated with this
      phenotype. METHODS: Patients with SSc who required supplemental nutrition
      (enteral or parenteral tube feeding) were compared to SSc patients with mild GI
      symptoms in a cross-sectional analysis. The association between severe GI
      dysmotility and clinical and serologic features was examined using logistic
      regression. Baseline data were examined to determine predictors of developing
      severe GI dysfunction using Cox regression. RESULTS: SSc patients with severe GI
      dysmotility (n = 66) were more likely than those patients with mild GI symptoms
      (n = 1,736) to be male (odds ratio [OR] 2.47 [95% confidence interval (95% CI)
      1.34-4.56]; P = 0.004), and to have myopathy (OR 5.53 [95% CI 2.82-10.82]; P <
      0.001), and sicca symptoms (OR 2.40 [95% CI 1.30-4.42]; P = 0.005), even after
      adjustment for potential confounders. Baseline features that were associated with
      the future development of severe GI dysfunction included male sex (hazard ratio
      [HR] 2.99 [95% CI 1.53-5.84]; P = 0.001) and myopathy (HR 5.08 [95% CI 2.21
      11.67]; P < 0.001). CONCLUSION: Distinct clinical features are present in SSc
      patients who are at risk of developing severe GI dysmotility. This finding is not
      only important clinically but also suggests that a unique pathologic process is
      at work in these patients.

PMID- 29193843
TI  - Polyoxometalate and Resin-Derived P-Doped Mo2 C@N-Doped Carbon as a Highly
      Efficient Hydrogen-Evolution Reaction Catalyst at All pH Values.
AB  - A new type of P-doped Mo2 C coated by N-doped carbon (P-Mo2 C@NC) has been
      successfully prepared by calcining a mixture of H3 [PMo12 O40 ] polyoxometalates
      (POMs) and urea-formaldehyde resin under an N2 atmosphere. Urea-formaldehyde
      resin not only serves as the carbon source to ensure carbonization but also
      facilitates the uniform distribution of POM precursors, which efficiently avoid
      the aggregation of Mo2 C particles at high temperatures. TEM analysis revealed
      that the average diameter of the Mo2 C particles was about 10 nm, which is coated
      by a few-layer N-doped carbon sheet. The as-prepared P-Mo2 C@NC displayed
      excellent hydrogen-evolution reaction (HER) performance and long-term stability
      in all pH environments. To reach a current density of 10 mA cm-2 , only 109, 159,
      and 83 mV were needed for P-Mo2 C@NC in 0.5 m H2 SO4 (pH 0), 0.1 m phosphate
      buffer (pH 7), and 1 m KOH (pH 14), respectively. This could provide a high-yield
      and low-cost method to prepare uniform nanosized molybdenum carbides with highly
      efficient and stable HER performance.

PMID- 29193844
TI  - Sodium bicarbonate-gelled chitosan beads as mechanically stable carriers for the
      covalent immobilization of enzymes.
AB  - The poor mechanical stability of chitosan has long impeded its industrial
      utilization as an immobilization carrier. In this study, the mechanical
      properties of chitosan beads were greatly improved through utilizing the slow
      rate of the sodium bicarbonate-induced chitosan gelation and combining it with
      the chemical cross-linking action of glutaraldehyde (GA). The GA-treated sodium
      bicarbonate-gelled chitosan beads exhibited much better mechanical properties and
      up to 2.45-fold higher observed activity of the immobilized enzyme (beta-D
      galactosidase (beta-gal)) when compared to the GA-treated sodium tripolyphosphate
      (TPP)-gelled chitosan beads. The differences between the sodium bicarbonate
      gelled and the TPP-gelled chitosan beads were proven visually and also via
      scanning electron microscopy, elemental analysis, and differential scanning
      calorimetry. Moreover, the optimum pH, the optimum temperature, the apparent Km ,
      and the apparent Vmax of the beta-gals immobilized onto the two aforementioned
      types of chitosan beads were determined and compared. A reusability study was
      also performed. This study proved the superiority of the sodium bicarbonate
      gelled chitosan beads as they retained 72.22 +/- 4.57% of their initial observed
      activity during the 13th reusability cycle whereas the TPP-gelled beads lost
      their activity during the first four reusability cycles, owing to their
      fragmentation. (c) 2017 American Institute of Chemical Engineers Biotechnol.
      Prog., 34:347-361, 2018.

PMID- 29193845
TI  - Anticancer Properties of Halogenated Pyrrolo[3,2-d]pyrimidines with Decreased
      Toxicity via N5 Substitution.
AB  - Halogenated pyrrolo[3,2-d]pyrimidine analogues have shown antiproliferative
      activity in recent studies, with cell accumulation occurring in the G2 /M stage
      without apoptosis. However, the mechanism of action and pharmacokinetic (PK)
      profile of these compounds has yet to be determined. To investigate the PK
      profile of these compounds, a series of halogenated pyrrolo[3,2-d]pyrimidine
      compounds was synthesized and first tested for activity in various cancer cell
      lines followed by a mouse model. EC50 values ranged from 0.014 to 14.5 MUm, and
      maximum tolerated doses (MTD) in mice were between 5 and 10 mg kg-1 . This
      indicates a wide variance in activity and toxicity that necessitates further
      study. To decrease toxicity, a second series of compounds was synthesized with N5
      alkyl substitutions in an effort to slow the rate of metabolism, which was
      thought to be leading to the toxicity. The N-substituted compounds demonstrated
      comparable cell line activity (EC50 values between 0.83-7.3 MUm) with
      significantly decreased toxicity (MTD=40 mg kg-1 ). Finally, the PK profile of
      the active N5-substituted compound shows a plasma half-life of 32.7 minutes, and
      rapid conversion into the parent unsubstituted analogue. Together, these data
      indicate that halogenated pyrrolo[3,2-d]pyrimidines present a promising lead into
      potent antiproliferative agents with tunable activity and toxicity, and rapid
      metabolism.

PMID- 29193846
TI  - Microprinted Stem Cell Niches Reveal Compounding Effect of Colony Size on Stromal
      Cells-Mediated Neural Differentiation.
AB  - Microenvironmental factors have a major impact on differentiation of embryonic
      stem cells (ESCs). Here, a novel phenomenon that size of ESC colonies has a
      significant regulatory role on stromal cells induced differentiation of ESCs to
      neural cells is reported. Using a robotic cell microprinting technology, defined
      densities of ESCs are confined within aqueous nanodrops over a layer of
      supporting stromal cells immersed in a second, immiscible aqueous phase to
      generate ESC colonies of defined sizes. Temporal protein and gene expression
      studies demonstrate that larger ESC colonies generate disproportionally more
      neural cells and longer neurite processes. Unlike previous studies that attribute
      neural differentiation of ESCs solely to interactions with stromal cells, it is
      found that increased intercellular signaling of ESCs significantly enhances
      neural differentiation. This study offers an approach to generate neural cells
      with improved efficiency for potential use in translational research.

PMID- 29193847
TI  - Genetic loss of diazepam binding inhibitor in mice impairs social interest.
AB  - Neuropsychiatric disorders in which reduced social interest is a common symptom,
      such as autism, depression, and anxiety, are frequently associated with genetic
      mutations affecting gamma-aminobutyric acid (GABA)ergic transmission.
      Benzodiazepine treatment, acting via GABA type-A receptors, improves social
      interaction in male mouse models with autism-like features. The protein diazepam
      binding inhibitor (DBI) can act as an endogenous benzodiazepine, but a role for
      DBI in social behavior has not been described. Here, we investigated the role of
      DBI in the social interest and recognition behavior of mice. The responses of DBI
      wild-type and knockout male and female mice to ovariectomized female wild-type
      mice (a neutral social stimulus) were evaluated in a habituation/dishabituation
      task. Both male and female knockout mice exhibited reduced social interest, and
      DBI knockout mice lacked the sex difference in social interest levels observed in
      wild-type mice, in which males showed higher social interest levels than females.
      The ability to discriminate between familiar and novel stimulus mice (social
      recognition) was not impaired in DBI-deficient mice of either sex. DBI knockouts
      could learn a rotarod motor task, and could discriminate between social and
      nonsocial odors. Both sexes of DBI knockout mice showed increased repetitive
      grooming behavior, but not in a manner that would account for the decrease in
      social investigation time. Genetic loss of DBI did not alter seminal vesicle
      weight, indicating that the social interest phenotype of males lacking DBI is not
      due to reduced circulating testosterone. Together, these studies show a novel
      role of DBI in driving social interest and motivation.

PMID- 29193848
TI  - Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety,
      Delivery Strategies, and Biomedical Applications.
AB  - Predetermining the physico-chemical properties, biosafety, and stimuli
      responsiveness of nanomaterials in biological environments is essential for safe
      and effective biomedical applications. At the forefront of biomedical research,
      mesoporous silica nanoparticles and mesoporous organosilica nanoparticles are
      increasingly investigated to predict their biological outcome by materials
      design. In this review, it is first chronicled that how the nanomaterial design
      of pure silica, partially hybridized organosilica, and fully hybridized
      organosilica (periodic mesoporous organosilicas) governs not only the physico
      chemical properties but also the biosafety of the nanoparticles. The impact of
      the hybridization on the biocompatibility, protein corona, biodistribution,
      biodegradability, and clearance of the silica-based particles is described. Then,
      the influence of the surface engineering, the framework hybridization, as well as
      the morphology of the particles, on the ability to load and controllably deliver
      drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external
      noninvasive stimuli (e.g., light, magnetic, ultrasound) are presented. To
      conclude, trends in the biomedical applications of silica and organosilica
      nanovectors are delineated, such as unconventional bioimaging techniques, large
      cargo delivery, combination therapy, gaseous molecule delivery, antimicrobial
      protection, and Alzheimer's disease therapy.

PMID- 29193849
TI  - Apparent transverse relaxation (R2*) on MRI as a method to differentiate
      treatment effect (pseudoprogression) versus progressive disease in chemoradiation
      for malignant glioma.
AB  - INTRODUCTION: Pseudoprogression (psPD) is a transient post-treatment imaging
      change that is commonly seen when treating glioma with chemotherapy and
      radiation. The use of apparent transverse relaxation rate (R2*), which is
      calculated from a contrast-free multi-echo gradient echo Magnetic Resonance
      Imaging (MRI) sequence, may allow for quantitative identification of patients
      with suspected psPD. METHODS: We acquired a multi-echo gradient echo sequence
      using a 3T-Siemens Prisma MRI. The signal decay through the echoes was fitted to
      provide the R2* coefficient. We segmented the T1 -gadolinium enhancing the image
      to provide a contrast enhancing lesion (CEL) and the FLAIR hyperintensity to
      provide a non-enhancing lesion (NEL). These regions of interest were applied to
      the multi-echo gradient echo to acquire a mean R2* within the CEL and NEL. We
      additionally acquired ADC data to attempt to corroborate our findings. RESULTS:
      We found that patients who later exhibited PD exhibited a higher R2* within the
      CEL as well as a higher ratio of CEL to NEL. Our data correctly distinguished
      pseudoprogression from treatment effect in 9/9 patients, while ADC corrected
      identified 7/9 patients using an absolute ADC of 1200 * 10-6  mm2 /s.
      CONCLUSIONS: Our method seems promising for the accurate identification of psPD,
      and the technique is amenable to evaluation in larger, multi-centre patient
      cohorts.

PMID- 29193850
TI  - Olfactory loss in chronic rhinosinusitis is associated with neuronal activation
      of c-Jun N-terminal kinase.
AB  - BACKGROUND: Olfactory inflammation in chronic rhinosinusitis (CRS) is associated
      with cytokines that may result in the death of olfactory sensory neurons. The
      principal signaling molecules involved in the apoptotic pathway are c-Jun N
      terminal kinases (JNK). Although the JNK pathway has emerged as a key player in
      programmed cell death in neuroinflammation, its specific role in CRS-associated
      olfactory loss has not been thoroughly investigated. METHODS: JNK activation was
      studied in human tissue samples from 9 control and 11 CRS patients by
      immunohistochemical staining for phosphorylated c-Jun. A mouse model of inducible
      olfactory cytokine expression was used to experimentally control inflammation and
      assess JNK activation over time. RESULTS: In patients with CRS, activation of c
      Jun is significantly increased relative to non-CRS control subjects, and there is
      an associated loss of sensory neurons. In the olfactory inflammation mouse model,
      prolonged induction of inflammation results in elevation of c-Jun expression and
      neuronal apoptosis. CONCLUSION: Activation of neuronal JNK is a feature of
      chronic olfactory inflammation that is associated with neuronal apoptosis. Given
      that inhibition of JNK activity is neuroprotective in other settings, antagonism
      of this pathway may have therapeutic potential in the management of inflammatory
      olfactory loss or other disorders linked to olfactory neuronal apoptosis.

PMID- 29193851
TI  - Survival of corneal nerve/sheath structures in organ-cultured donor corneas.
AB  - PURPOSE: To study the morphology of human corneal nerves in eye bank organ
      cultured corneas and in corneal grafts post-transplantation. METHODS: Thirty
      seven organ-cultured corneas were divided into: Group-A, anterior 300-400 MUm of
      20 corneas used for Descemets stripping endothelial keratoplasty, and Group-B, 17
      full-thickness corneas unsuitable for transplantation. Corneas whole mounts were
      stained for nerves using acetylcholinesterase technique and examined by
      NanoZoomer digital pathology microscope. Central and sub-Bowman's stromal nerves
      and the sub-basal nerve plexus including perforation sites and terminal bulbs
      were studied. Ten eyes were imaged following penetrating keratoplasty using in
      vivo confocal microscopy (IVCM) for the presence of sub-basal and stromal nerves
      at 1, 4-5 and 7-8 weeks postoperatively (five eyes) and in all the other five
      eyes, the final follow-up was at 12 weeks. RESULTS: Fifteen of twenty (75%)
      corneas had stromal nerves in Group-A and 15 of 17 (88.2%) in Group-B. Average
      number of stromal nerves entering peripherally were 9.1 (range: 1-36). 7.5 in
      Group-A and 10.8 in Group-B. Central stromal nerves were seen in eight samples in
      Group-A and nine in Group-B. Many stromal nerves terminated abruptly without
      demonstrable continuity through Bowman's membrane. No terminal bulbs or sub-basal
      nerves were detected. In-vivo confocal microscopy (IVCM) showed 4 of 5 in 9 of 10
      (90%) donor corneas had stromal nerves 1 week postoperatively, which remained
      present in 8 of 10 (80%) corneas at 4-5 weeks and in 9 of 10 (90%) at 7-8 weeks
      postoperatively. All 5 corneas analysed at 12 weeks showed the same stromal
      nerves from 1 to 12 weeks postoperatively. Sub-basal nerves were absent in all
      corneas over the 12-week study period. CONCLUSION: This study provides further
      insight into the behaviour of corneal nerves in transplanted corneas. Corneal
      stromal nerves/nerve-sheaths are preserved in organ-cultured eye bank eyes and
      persist post-transplantation up to 3 months. These could provide directional
      guidance to regenerating nerves from host stroma.

PMID- 29193852
TI  - Frequency-Domain Response Analysis for Quantitative Systems Pharmacology Models.
AB  - Drug dosing regimen can significantly impact drug effect and, thus, the success
      of treatments. Nevertheless, trial and error is still the most commonly used
      method by conventional pharmacometric approaches to optimize dosing regimen. In
      this tutorial, we utilize four distinct classes of quantitative systems
      pharmacology models to introduce frequency-domain response analysis, a method
      widely used in electrical and control engineering that allows the analytical
      optimization of drug treatment regimen from the dynamics of the model.

PMID- 29193854
TI  - Reply.

PMID- 29193853
TI  - Malaria in India: The Need for New Targets for Diagnosis and Detection of
      Plasmodium vivax.
AB  - Plasmodium vivax is a protozoan parasite that is one of the causative agents of
      human malaria. Due to several occult features of its life cycle, P. vivax
      threatens to be a problem for the recent efforts toward elimination of malaria
      globally. With an emphasis on malaria elimination goals, the authors summarize
      the major gaps in P. vivax diagnosis and describe how proteomics technologies
      have begun to contribute toward the discovery of antigens that could be used for
      various technology platforms and applications. The authors suggest areas where,
      in the future, proteomics technologies could fill in gaps in P. vivax diagnosis
      that have proved difficult. The discovery of new parasite antigens, host
      responses, and immune signatures using proteomics technologies will be a key part
      of the global malaria elimination efforts.

PMID- 29193855
TI  - Sulfanilic acid-modified chitosan mini-spheres and their application for lysozyme
      purification from egg white.
AB  - A cation exchange matrix with zwitterionic and multimodal properties was
      synthesized by a simple reaction sequence coupling sulfanilic acid to a chitosan
      based support. The novel chromatographic matrix was physico-chemically
      characterized by ss-NMR and zeta potential, and its chromatographic performance
      was evaluated for lysozyme purification from diluted egg white. The maximum
      adsorption capacity, calculated according to Langmuir adsorption isotherm, was
      50.07 +/- 1.47 mg g-1 while the dissociation constant was 0.074 +/- 0.012 mg mL-1
      . The process for lysozyme purification from egg white was optimized, with 81.9%
      yield and a purity degree of 86.5%, according to RP-HPLC analysis. This work
      shows novel possible applications of chitosan based materials. The simple
      synthesis reactions combined with the simple mode of use of the chitosan matrix
      represents a novel method to purify proteins from raw starting materials. (c)
      2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:387-396,
      2018.

PMID- 29193857
TI  - Prenatal and postnatal development of the mammalian ear.
AB  - The ear can be subdivided into three distinct parts, each with significantly
      distinct structural and functional differences, the outer, middle, and inner ear,
      the latter housing the specialized sensory hair cells that act as transducers.
      There are numerous manuscripts documenting the anatomical development of the
      inner, middle, and outer ear in humans, rodents, chick, and zebrafish, dating
      back to the early 20th Century, and these developmental processes of these
      components are further compared in a number of review articles (Anthwal &
      Thompson, ; Basch, Brown, Jen, & Groves, ; Sai & Ladher, ). This article presents
      a review of both pre- and postnatal development of the inner ear, discusses
      recent molecular genetic advances toward our understanding of hair cells
      responsible for the sensory functions of the inner ear. Finally, a survey of
      comparative ear biology is used to pull together our understanding of the species
      differences, similarities, and key time points of definitive organ development of
      the ear.

PMID- 29193856
TI  - Physical forces modulate cell differentiation and proliferation processes.
AB  - Currently, the predominant hypothesis explains cellular differentiation and
      behaviour as an essentially genetically driven intracellular process, suggesting
      a gene-centrism paradigm. However, although many living species genetic has now
      been described, there is still a large gap between the genetic information
      interpretation and cell behaviour prediction. Indeed, the physical mechanisms
      underlying the cell differentiation and proliferation, which are now known or
      suspected to guide such as the flow of energy through cells and tissues, have
      been often overlooked. We thus here propose a complementary conceptual framework
      towards the development of an energy-oriented classification of cell properties,
      that is, a mitochondria-centrism hypothesis based on physical forces-driven
      principles. A literature review on the physical-biological interactions in a
      number of various biological processes is analysed from the point of view of the
      fluid and solid mechanics, electricity and thermodynamics. There is consistent
      evidence that physical forces control cell proliferation and differentiation. We
      propose that physical forces interfere with the cell metabolism mostly at the
      level of the mitochondria, which in turn control gene expression. The present
      perspective points towards a paradigm shift complement in biology.

PMID- 29193858
TI  - Exophiala phaeomuriformis keratitis in a subarctic climate region: a case report.
AB  - PURPOSE: To report a case of Exophiala phaeomuriformis mycotic keratitis in a
      patient from a subarctic climate region. Dematiaceous fungi (black yeasts) have
      been gaining importance as corneal keratitis and ulcer causative agents in
      certain regions, but no cases have been described in Scandinavia. METHODS: Case
      report of a patient with a persistent corneal erosion that eventually presented a
      brown-pigmented infiltrate. The patient had a history of several months of
      topical therapy comprising medication for glaucoma, corticosteroids and
      antibiotics. A therapeutic contact lens was used, and amniotic membrane
      transplantation was performed before the development of the pigmented infiltrate.
      RESULTS: Exophiala phaeomuriformis was identified on the microbiological cultures
      from the surgically obtained infiltrate scrapes. The patient responded to topical
      amphotericin and fluconazole, the erosion was cured and a stromal scar subsided.
      During follow-up, sequential slit-lamp images and anterior segment optical
      coherence tomography (OCT) scans were obtained. CONCLUSION: This is the first
      described case of keratitis caused by E. phaeomuriformis in a subarctic region,
      the first in Europe and, to our knowledge, the second reported case in the
      literature. It is important to remember that superficial corneal brown-pigmented
      infiltrates should raise the suspicion of an unusual fungal infection even in
      this climate. This is particularly important in patients with ocular surface
      disease treated with steroids and antibiotics for a long time.

PMID- 29193859
TI  - Comparative evaluation of salivary hepatocyte growth factor in smokers and non
      smokers with chronic periodontitis.
AB  - AIM: Hepatocyte growth factor (HGF) is a multifunctional cytokine with a wide
      range of actions, and plays a role in periodontal disease (PD) progression.
      Smoking significantly increases the risk for PD progression. Thus, aim of the
      present study was to estimate salivary HGF levels of non-smokers and smokers with
      chronic periodontitis (CP) and to compare its levels before and after therapy.
      METHODS: A total of 75 participants were recruited and divided into three groups:
      group 1 included 25 healthy participants, group 2 included 25 non-smokers with
      CP, and group 3 included 25 smokers with CP. Salivary HGF levels were estimated
      by enzyme-linked immunosorbent assay and correlated with clinical parameters
      before and after treatment. RESULTS: Salivary HGF levels of non-smokers and
      smokers with CP were significantly higher than the control group. There was a
      significant reduction in salivary HGF in smokers and non-smokers with CP after
      non-surgical periodontal therapy (NSPT). CONCLUSION: Salivary HGF levels
      positively correlated with PD progression and smoking status. A significant
      reduction in HGF levels was seen after NSPT. Thus, within limits, it can be
      suggested that HGF plays a role in PD progression and can be used as a diagnostic
      biomarker to detect disease activity. Salivary HGF levels could also be useful to
      monitor response to periodontal therapy.

PMID- 29193860
TI  - Higher Coronary Plaque Burden in Psoriatic Arthritis Is Independent of Metabolic
      Syndrome and Associated With Underlying Disease Severity.
AB  - OBJECTIVE: To examine the effect of metabolic syndrome and psoriatic disease
      related variables on coronary plaque burden in psoriatic arthritis (PsA)
      patients. METHODS: Fifty PsA patients without symptoms of coronary artery disease
      (CAD) (25 with metabolic syndrome and 25 without metabolic syndrome) and 50 age-
      and sex-matched controls underwent 64-slice coronary computed tomography
      angiography. Plaque localization, segment involvement score (SIS), segment
      stenosis score (SSS), and total plaque volume (TPV) were calculated. Plaques were
      classified as calcified, mixed, or noncalcified. Kruskal-Wallis test, rank
      correlations, and linear regression analyses were used to study the relationship
      between PsA, metabolic syndrome, and plaque burden. RESULTS: Plaques were found
      in 76% of PsA patients versus 44% of controls (P = 0.001), and a higher
      proportion of patients with PsA had affected coronary vessels (P = 0.007). SIS,
      SSS, and TPV were greater in PsA patients than controls (P = 0.003, P = 0.001,
      and P <= 0.001, respectively). More PsA patients had mixed plaques, and mixed
      plaque volume was higher than in controls (P < 0.001). PsA patients with
      metabolic syndrome and those without metabolic syndrome had similar plaque
      burdens and types. SIS, SSS, and TPV did not show significant relationships with
      features of metabolic syndrome, but did significantly correlate with disease
      activity measures. TPV was associated with a diagnosis of PsA (B = 0.865, P =
      0.008), but not with metabolic syndrome. Age, highest C-reactive protein level,
      highest swollen joint count, disease duration, and plasma glucose level were
      independent predictors of higher plaque burden in PsA. CONCLUSION: PsA is
      associated with accelerated coronary plaque formation, particularly mixed
      plaques, independent of metabolic disease. Psoriatic disease activity and
      severity may predict coronary plaque burden better than traditional risk factors.

PMID- 29193861
TI  - The adenosine A2A receptor agonist, CGS 21680, attenuates a probabilistic
      reversal learning deficit and elevated grooming behavior in BTBR mice.
AB  - : Restricted interests and repetitive behaviors (RRBs) are a defining feature of
      autism spectrum disorder (ASD). To date there are limited options for treating
      this core symptomology. Treatments that stimulate adenosine A2A receptors may
      represent a promising approach for reducing RRBs in ASD. This is because A2A
      receptors are expressed on striatal neurons of the basal ganglia indirect
      pathway. Under activation of this pathway has been associated with RRBs while
      activation of A2A receptors leads to increased activity of the indirect basal
      ganglia pathway. The present studies investigated whether acute, systemic
      treatment with CGS21680, an A2A receptor agonist attenuates elevated self
      grooming and a probabilistic reversal learning deficit in the BTBR T+ Itpr3tf /J
      (BTBR) mouse model of idiopathic autism. The effects of this treatment were also
      investigated in C57BL/6J (B6) mice as a comparison strain. Using a spatial
      reversal learning test with 80/20 probabilistic feedback, comparable to one in
      which ASD individuals exhibit deficits, CGS 21680 (0.005 and 0.01mg/kg)
      attenuated a reversal learning deficit in BTBR mice. Enhancement in probabilistic
      reversal learning performance resulted from CGS 21680 improving the consistent
      maintenance of new adaptive behavioral choice patterns after reversal. CGS 21680
      at 0.01 mg, but not 0.005 mg, also reduced self-grooming behavior in BTBR mice.
      CGS 21680 did not affect self-grooming or reversal learning in B6 mice. These
      findings demonstrate that A2A receptor agonists may be a promising receptor
      target in the treatment of RRBs in ASD. Autism Res 2018, 11: 223-233. (c) 2017
      International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:
      The present experiments determined whether the drug, CGS 21680, that facilitates
      activation of adenosine A2A receptors in the brain, would reduce repetitive and
      inflexible behaviors in the BTBR mouse model of idiopathic autism. CGS 21680
      treatment in BTBR mice reduced repetitive and inflexible behaviors. In the
      control C57BL/6J (B6) mouse strain, CGS 21680 did not affect performance. These
      findings suggest that stimulation of brain adenosine A2A receptors may be a
      promising therapeutic strategy in ASD.

PMID- 29193862
TI  - Lack of Effect of Teriparatide on Joint Erosions in Rheumatoid Arthritis Is an
      Expected Result: Comment on the Article by Solomon et al.

PMID- 29193863
TI  - Sublethal effects of subzero temperatures on the light brown apple moth, Epiphyas
      postvittana: fitness costs in response to partial freezing.
AB  - Population responses to environmental extremes often dictate the bounds to
      species' distributions. However, population dynamics at, or near, those range
      limits may also be affected by sublethal effects. We exposed late instars and
      pupae of an invasive leafroller, Epiphyas postvittana (Walker) (Lepidoptera:
      Tortricidae), to cold temperatures and measured the effects of exposure on
      subsequent survivorship, development, and reproduction. Cold temperature was
      applied as acute exposure to -10  degrees C (a low, but not immediately lethal
      temperature for this species) or the onset of freezing (the peak of the
      supercooling point exotherm). Survival was defined as the ability to successfully
      eclose as an adult. We measured immature development times, pupal mass, and adult
      longevity as proxies of fitness in survivors. Additionally, surviving insects
      were mated with individuals that had not been exposed to cold to measure
      fertility. There was no difference between the proportion of larvae or pupae that
      survived acute exposure to -10  degrees C and those exposed to the control
      temperature. Approximately 17% of larvae and 8% of pupae survived brief periods
      with internal ice formation and continued development to become reproductively
      viable adults. Importantly, surviving the onset of freezing came with significant
      fitness costs but not to exposure to -10  degrees C; most insects that survived
      partial freezing had lower fertility and shorter adult lifespans than either the 
      10  degrees C or control group. These results are discussed within the context of
      forecasting invasive insect distributions.

PMID- 29193864
TI  - Are the spin doctors winning?

PMID- 29193865
TI  - Maternal Chlamydia infection during pregnancy among younger mothers and risk of
      gastroschisis in singleton offspring.
AB  - BACKGROUND: Prevalence of gastroschisis has been increasing in the United States
      (US) since 1980s. Genital infection with Chlamydia has also been increasing in
      prevalence, particularly among younger women. The etiology of gastroschisis is
      unknown. Ongoing research suggests multiple causal factors may be involved,
      including Chlamydia infection in mothers during pregnancy. METHODS: Using birth
      certificate data from 2014 US vital records, we conducted a population-based case
      control study to examine the association between prenatal Chlamydia exposure in
      young women (16-25 years of age) and gastroschisis in singleton offspring. Cases
      consisted of live births with gastroschisis, and controls had no major birth
      defects reported in their birth certificate. Logistic regression analysis was
      used to estimate crude and adjusted odds ratios (cOR and aOR) and 95% confidence
      intervals (CI). RESULTS: There were 809 cases (95.6% were isolated cases) and
      1,260,293 controls. Chlamydia during pregnancy was reported in 4.5% of case and
      3.6% control mothers (p = .21). Case mothers were significantly more likely to be
      younger (16-20 years of age) at the time of delivery compared to control mothers
      (p < .0001). We found no significant association between Chlamydia infection
      during pregnancy and gastroschisis (cOR = 1.24; 95% CI = 0.89-1.73 and aOR =
      1.06; 95% CI: 0.66-1.70). CONCLUSION: With the caveat of possible
      misclassification of exposure and outcome variables in birth certificate data, we
      found no significant association between prenatal exposure to Chlamydia and
      gastroschisis in the offspring born to younger mothers. Future studies should
      refine measures by focusing on relevant risk period and biomarkers.

PMID- 29193866
TI  - Revisit the Cavernous Sinus from Fetus to Adult-New and Old Data.
AB  - This article highlighted three advances in the study of the cavernous sinus: (1)
      the initial formation of the sinus reticulum in early development of the sphenoid
      bone before ossification (2) extension of reticulum of the sinus and connection
      with other venules, and (3) the cavernous sinus and the nerves evolved inside
      this sinus during gestation, for example, the trigeminal nerve already formed
      bundles of motor and parasympathetic components during fetal development. This
      ontogenetic study further confirmed the cavernous sinus is not a single or a dual
      set of sinuses, but a group of extensions of venous sinuses or sinusoids. These
      new insights were integrated with previous understandings of the cavernous sinus
      to form this review article. Anat Rec, 301:819-824, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29193867
TI  - Improved safety margin for embryotoxicity in rats for the new endoperoxide
      artefenomel (OZ439) as compared to artesunate.
AB  - BACKGROUND: Combination medicines including an artemisinin are the mainstay of
      antimalarial therapy. Artemisinins are potent embryotoxicants in animal species
      due to their trioxane moiety. METHODS: As part of its development, the new
      synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole
      embryo culture and in rat embryo-fetal toxicity studies with dosing throughout
      organogenesis or with a single dose on Gestational Day (GD) 12. The single-dose
      studies included groups treated with artesunate to allow a direct comparison of
      the embryotoxicity of the two antimalarials and included toxicokinetics
      hematology and histological examination of embryos. In addition, the distribution
      of artefenomel-related material in plasma was determined after the administration
      of 14 C-artefenomel. RESULTS: Artefenomel and artesunate showed similar patterns
      of embryotoxicity including cardiovascular defects and resorption with a steep
      dose-response. They both also caused a depletion of circulating embryonic
      erythroblasts both in vitro and in vivo and decreases in maternal reticulocyte
      count. However, artefenomel was ~250-fold less potent than the active metabolite
      of artesunate (dihydroartemisinin) as an embryotoxicant in vitro. The safety
      margin (based on AUC) for artefenomel administered on GD 12 was approximately 100
      fold greater than that for artesunate. Also, unlike artesunate, artefenomel was
      not a selective developmental toxicant. CONCLUSIONS: The lesser embryotoxicity of
      artefenomel is likely linked to its original design which included two blocking
      side groups that had been introduced to lower the reactivity with ferrous iron.
      Our data support the hypothesis that artefenomel's improved safety margin is
      linked to a lower potential for inhibiting heme biosynthesis in embryonic
      erythroblasts.

PMID- 29193868
TI  - Xanthomonas axonopodis pv. punicae uses XopL effector to suppress pomegranate
      immunity.
AB  - Xanthomonas axonopodis pv. punicae (Xap) causing bacterial blight is an important
      pathogen that incurs significant losses to the exportability of pomegranate. Xap
      uses the Xop TTSS-effector, via the type three secretion system, to suppress
      pomegranate immunity. Here, we investigate the role of XopL during blight
      pathogenesis. We observed that XopL is essential for its in planta growth and
      full virulence. Leaves inoculated with Xap DeltaxopL produced restricted water
      soaked lesions compared to those inoculated with wild-type Xap. XopL supports Xap
      for its sustained multiplication in pomegranate by suppressing the plant cell
      death (PCD) event. We further demonstrated that XopL suppresses immune responses,
      such as callose deposition and production of reactive oxygen species (ROS). RT
      qPCR analysis revealed that immune responsive genes were upregulated when
      challenged with Xap DeltaxopL, whereas upregulation of such genes was compromised
      in the complemented strain containing the xopL gene. The transiently expressed
      XopL::EYFP fusion protein was localized to the plasma membrane, indicating the
      possible site of its action. Altogether, this study highlights that XopL is an
      important TTSS-effector of Xap that suppresses plant immune responses, including
      PCD, presumably to support the multiplication of Xap for a sufficient time-period
      during blight disease development.

PMID- 29193870
TI  - Strain engineering to reduce acetate accumulation during microaerobic growth
      conditions in Escherichia coli.
AB  - Microaerobic (oxygen limited) conditions are advantageous for several industrial
      applications since a majority of the carbon atoms can be directed for synthesis
      of desired products. Oxygen limited conditions, however, can result in high
      levels of undesirable by-products such as acetate, which subsequently can have an
      impact on biomass and product yields. The molecular mechanisms involved in
      acetate accumulation under oxygen limited conditions are not well understood. Our
      results indicate that a majority of the genetic modifications known to decrease
      acetate under aerobic conditions results in similar or even higher acetate under
      oxygen limitation. Deletion of arcA, whose gene product is a global
      transcriptional regulator, was the only modification among those evaluated that
      significantly decreased acetate under both transient and prolonged oxygen
      limitation. Transcriptome results indicate that the arcA deletion results in an
      increased expression of the operon involving acs and actP (whose gene products
      are involved in acetate assimilation and uptake respectively) and some genes in
      the TCA cycle, thereby promoting increased acetate assimilation. These results
      provide useful cues for strain design for improved manufacturing of
      biopharmaceuticals under oxygen limited conditions. (c) 2017 American Institute
      of Chemical Engineers Biotechnol. Prog., 34:303-314, 2018.

PMID- 29193869
TI  - CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk
      Loci in Patients With Untreated Early Arthritis: Implications for Causal Gene
      Identification.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a genetically complex disease of immune
      dysregulation. This study sought to gain further insight into the genetic risk
      mechanisms of RA by conducting an expression quantitative trait locus (eQTL)
      analysis of confirmed genetic risk loci in CD4+ T cells and B cells from
      carefully phenotyped patients with early arthritis who were naive to therapeutic
      immunomodulation. METHODS: RNA and DNA were isolated from purified B and/or CD4+
      T cells obtained from the peripheral blood of 344 patients with early arthritis.
      Genotyping and global gene expression measurements were carried out using
      Illumina BeadChip microarrays. Variants in linkage disequilibrium (LD) with non
      HLA RA single-nucleotide polymorphisms (defined as r2 >= 0.8) were analyzed,
      seeking evidence of cis- or trans-eQTLs according to whether the associated
      probes were or were not within 4 Mb of these LD blocks. RESULTS: Genes subject to
      cis-eQTL effects that were common to both CD4+ and B lymphocytes at RA risk loci
      were FADS1, FADS2, BLK, FCRL3, ORMDL3, PPIL3, and GSDMB. In contrast, those
      acting on METTL21B, JAZF1, IKZF3, and PADI4 were unique to CD4+ lymphocytes, with
      the latter candidate risk gene being identified for the first time in this cell
      subset. B lymphocyte-specific eQTLs for SYNGR1 and CD83 were also found. At the
      8p23 BLK-FAM167A locus, adjacent genes were subject to eQTLs whose activity
      differed markedly between cell types; in particular, the FAM167A effect displayed
      striking B lymphocyte specificity. No trans-eQTLs approached experiment-wide
      significance, and linear modeling did not identify a significant influence of
      biologic covariates on cis-eQTL effect sizes. CONCLUSION: These findings further
      refine the understanding of candidate causal genes in RA pathogenesis, thus
      providing an important platform from which downstream functional studies,
      directed toward particular cell types, may be prioritized.

PMID- 29193871
TI  - Dynamic and Responsive Growth Factor Delivery from Electrospun and Hydrogel
      Tissue Engineering Materials.
AB  - Tissue engineering scaffolds are designed to mimic physical, chemical, and
      biological features of the extracellular matrix, thereby providing a constant
      support that is crucial to improved regenerative medicine outcomes. Beyond
      mechanical and structural support, the next generation of these materials must
      also consider the more dynamic presentation and delivery of drugs or growth
      factors to guide new and regenerating tissue development. These two aspects are
      explored expansively separately, but they must interact synergistically to
      achieve optimal regeneration. This review explores common tissue engineering
      materials types, electrospun polymers and hydrogels, and strategies used for
      incorporating drug delivery systems into these scaffolds.

PMID- 29193872
TI  - The Impact of Adhesion Molecules on the In Vitro Culture and Differentiation of
      Stem Cells.
AB  - The term "cell adhesion" represents cell-cell interactions and the interaction
      between the cell and the extracellular matrix (ECM). These interactions are
      crucial for the development of the stem cells niche to determine stem cell shape.
      The ECM is considered as a natural niche for cell residence. Cell adhesion
      molecules (CAMs) enable cell-cell interactions and the interactions between the
      cell and ECM via various mechanisms, such as trans-interaction and the
      heterophilic interactions. These interactions promote a broad spectrum of cell
      signaling that directly or indirectly modulates stem cell proliferation, self
      renewal property, adhesion, and multilineage differentiation. Over many years,
      animal-derived feeder layers and culture components have been used for stem cell
      culture, which produces stem cells unsuitable for clinical applications in the
      regenerative medicine. This review briefly describes the stages of the
      development of stem cell culture toward a defined condition and the drawbacks of
      using animal-derived culture components. Stem cell niche-derived and ECM-derived
      adhesion molecules and their detailed impact on stem cell adhesion and functions
      will be discussed. Efficient and novel adhesion molecules for stem cell culture
      and differentiation are needed for further large-scale applications in tissue
      regeneration.

PMID- 29193873
TI  - Simple and accurate method for determining dissolved inorganic carbon in
      environmental water by reaction headspace gas chromatography.
AB  - We investigate a simple and accurate method for quantitatively analyzing
      dissolved inorganic carbon in environmental water by reaction headspace gas
      chromatography. The neutralization reaction between the inorganic carbon species
      (i.e. bicarbonate ions and carbonate ions) in environmental water and
      hydrochloric acid is carried out in a sealed headspace vial, and the carbon
      dioxide formed from the neutralization reaction, the self-decomposition of
      carbonic acid, and dissolved carbon dioxide in environmental water is then
      analyzed by headspace gas chromatography. The data show that the headspace gas
      chromatography method has good precision (relative standard deviation <= 1.63%)
      and accuracy (relative differences <= 5.81% compared with the coulometric
      titration technique). The headspace gas chromatography method is simple,
      reliable, and can be well applied in the dissolved inorganic carbon detection in
      environmental water.

PMID- 29193874
TI  - A factorial design to identify process parameters affecting whole mechanically
      disrupted rat pancreata in a perfusion bioreactor.
AB  - Few studies report whole pancreatic tissue culture, as it is a difficult task
      using traditional culture methods. Here, a factorial design was used to
      investigate the singular and combinational effects of flow, dissolved oxygen
      concentration (D.O.) and pulsation on whole mechanically disrupted rat pancreata
      in a perfusion bioreactor. Whole rat pancreata were cultured for 72 h under
      defined bioreactor process conditions. Secreted insulin was measured and
      histological (haematoxylin and eosin (H&E)) as well as immunofluorescent insulin
      staining were performed and quantified. The combination of flow and D.O. had the
      most significant effect on secreted insulin at 5 h and 24 h. The D.O. had the
      biggest effect on tissue histological quality, and pulsation had the biggest
      effect on the number of insulin-positive structures. Based on the factorial
      design analysis, bioreactor conditions using high flow, low D.O., and pulsation
      were selected to further study glucose-stimulated insulin secretion. Here,
      mechanically disrupted rat pancreata were cultured for 24 h under these
      bioreactor conditions and were then challenged with high glucose concentration
      for 6 h and high glucose + IBMX (an insulin secretagogue) for a further 6 h.
      These cultures secreted insulin in response to high glucose concentration in the
      first 6 h, however stimulated-insulin secretion was markedly weaker in response
      to high glucose concentration + IBMX thereafter. After this bioreactor culture
      period, higher tissue metabolic activity was found compared to that of non
      bioreacted static controls. More insulin- and glucagon-positive structures, and
      extensive intact endothelial structures were observed compared to non-bioreacted
      static cultures. H&E staining revealed more intact tissue compared to static
      cultures. (c) 2017 American Institute of Chemical Engineers Biotechnol. Prog.,
      34:432-444, 2018.

PMID- 29193875
TI  - Dabigatran inhibits intravitreal thrombin activity.
AB  - PURPOSE: Proliferative vitreoretinopathy (PVR) is a vitreoretinal disorder in
      which retinal pigment epithelial (RPE) cell activation contributes to both
      formation of fibrotic retinal membranes and inflammation. Vitreous of patients
      with PVR contains increased thrombin activity which induces profibrotic and
      proinflammatory programs in RPE cells. Inhibition of intravitreal thrombin
      activity may thus represent a therapeutic option for PVR. In this study, we
      examined the capacity of the clinically available direct thrombin inhibitor
      dabigatran to inhibit thrombin activity in vitreous fluids. METHODS: ARPE-19
      cells were cultured with the following: (i) thrombin, (ii) vitreous without
      thrombin activity and (iii) vitreous with elevated thrombin activity (PVR samples
      and thrombin spiked vitreous) either in the presence or absence of dabigatran
      (range: 10-5 to 10-7  M). Subsequently, CCL2, CXCL8, GMCSF, IL6 and PDGFB mRNA
      expression levels were determined by RQ-PCR and protein levels of 27 cytokines,
      chemokines and growth factors were detected in culture supernatants using a
      multiplex approach. In addition, the capacity of vitreous fluids obtained from
      patients after oral dabigatran intake was tested in an in vitro thrombin activity
      assay. RESULTS: Thrombin and vitreous fluids containing thrombin activity induced
      CCL2, CXCL8, GM-CSF, IL-6 and PDGF-BB expression by ARPE-19 cells, which was
      inhibited by dabigatran. In addition, dabigatran that reached the vitreous after
      repeated oral intake did inhibit thrombin activity in the in vitro activity
      assay. CONCLUSION: Proliferative vitreoretinopathy (PVR) is associated with
      increased intravitreal thrombin activity that activates profibrotic and
      proinflammatory pathways in RPE cells. Our findings provide evidence that this
      activation pathway can potentially be inhibited by dabigatran.

PMID- 29193876
TI  - Cell-Based Drug Delivery and Use of Nano-and Microcarriers for Cell
      Functionalization.
AB  - Cell functionalization with recently developed various nano- and microcarriers
      for therapeutics has significantly expanded the application of cell therapy and
      targeted drug delivery for the effective treatment of a number of diseases. The
      aim of this progress report is to review the most recent advances in cell-based
      drug vehicles designed as biological transporter platforms for the targeted
      delivery of different drugs. For the design of cell-based drug vehicles,
      different pathways of cell functionalization, such as covalent and noncovalent
      surface modifications, internalization of carriers are considered in greater
      detail together with approaches for cell visualization in vivo. In addition,
      several animal models for the study of cell-assisted drug delivery are discussed.
      Finally, possible future developments and applications of cell-assisted drug
      vehicles toward targeted transport of drugs to a designated location with no or
      minimal immune response and toxicity are addressed in light of new pathways in
      the field of nanomedicine.

PMID- 29193877
TI  - Effects of probiotics on ghrelin and lungs in children with acute lung injury: A
      double-blind randomized, controlled trial.
AB  - AIM: To assess the effects of probiotics on serum ghrelin levels and protection
      for lungs in children with acute lung injury (ALI). METHODS: This study was
      performed as a double-blind, randomized, and controlled trial in a pediatric
      intensive care unit (PICU). The eligible children with ALI were assigned to
      either probiotic treatment or an identical placebo for 10 days. Serum ghrelin, SP
      A(surfactant protein-A), TNF-alpha, and IL-6 concentrations were assessed at
      baseline and at the end of trial. Meanwhile, pulmonary function test and
      echocardiography were examined, then VPEF (volume to peak tidal expiratory flow),
      TPEF/TE (the ratio of time taken to reach peak expiratory flow to total
      expiratory time), MAP (mean arterial pressure), and PAP (pulmonary artery
      pressure) were recorded. RESULTS: Eighty participants fulfilled the study
      requirements with 40 children for each group. The groups were comparable in
      baseline characteristics. Serum SP-A, TNF-alpha, and IL-6 levels in the probiotic
      group were 212.6 +/- 52.9 ng/mL, 401.9 +/- 56.4 pg/mL, and 245.1 +/- 55.1 pg/mL
      on day 10, respectively, significantly lower levels compared to the control group
      where the same parameters were 248.2 +/- 57 ng/mL, 449.4 +/- 60.1 pg/mL, and
      308.3 +/- 92.2 pg/mL (P < 0.01). However, ghrelin concentrations were elevated in
      the intervention group (P < 0.05). On measurement of pulmonary function, the
      probiotic group demonstrated a VPEF of 26.1 +/- 4.2 mL and TPEF/TE of 29.1 +/-
      4.7%, which were higher than the control group (24.7 +/- 4.3 mL and 26.9 +/-
      4.7%, respectively) (P < 0.05). MAP and PAP also improved in the probiotic group
      (P < 0.05). Furthermore, ghrelin, SP-A, TNF-alpha, IL-6, and PAP were negatively
      correlated. Positive correlations were found between ghrelin, TPEF/TE, and MAP.
      There were no probiotic-associated adverse events during the observation.
      CONCLUSION: Probiotics administrated to children with ALI alleviates the
      inflammation of lungs, improves pulmonary function and circulation by ghrelin.

PMID- 29193878
TI  - Development of a transendothelial shuttle by macrophage modification.
AB  - One of the limiting factors in tissue regeneration, particularly in the context
      of chronic disease such as myodystrophy, motor neuron disease, sarcopenia, and
      cardiovascular disease, is limited availability of stem cells. We propose
      employing autologous macrophages to deliver stem cells, thereby facilitating
      tissue regeneration, by a novel and relatively non-invasive therapeutic
      intervention. Circulatory monocytic cells of M1 phenotype have capacity for
      transendothelial migration to infiltrate damaged tissue, making them ideal
      delivery vehicles. However, in order to deliver viable stem cells, these
      macrophages must undergo phagosome maturation arrest. Our aim was to induce
      phagosome maturation arrest in prepolarised M1 macrophages, whilst maintaining
      capacity for phagocytic engulfment (including phagosome formation) and
      transendothelial migration. Primary human M1 macrophages were treated with a
      wortmannin-concanamycin A-chloroquine cocktail to induce arrest. Modified cells
      were allowed to ingest 4.5 MUm protein-coated fluorescent latex beads (simulated
      stem cells), before migratory capacity in response to MCP-1 was assessed over a 2
      hr period in a Transwell co-culture system. Data indicate that phagosome
      acidification (as indicated by pHrodo(r)) was prevented in treated cells,
      effectively limiting digestion of ingested "cargo" (1.23 +/- 0.26% vs. 7.52 +/-
      0.98% in controls; p < .0001). Neither phagocytic engulfment capacity (68.67 +/-
      3.51% vs. 61.19 +/- 4.68%) nor migratory capacity (70.14 +/- 12.6 vs. 72.86 +/-
      16.0 migrated cells per well) was compromised. We conclude that macrophages were
      successfully modified into transendothelial delivery vehicles, without
      compromising required functionality. This delivery system can be exploited to
      develop a novel method for focussed stem cell and/or drug delivery.

PMID- 29193879
TI  - Organ Bioprinting: Are We There Yet?
AB  - About 15 years ago, bioprinting was coined as one of the ultimate solutions to
      engineer vascularized tissues, which was impossible to accomplish using the
      conventional tissue fabrication approaches. With the advances of 3D-printing
      technology during the past decades, one may expect 3D bioprinting being developed
      as much as 3D printing. Unfortunately, this is not the case. The printing
      principles of bioprinting are dramatically different from those applied in
      industrialized 3D printing, as they have to take the living components into
      account. While the conventional 3D-printing technologies are actually applied for
      biological or biomedical applications, true 3D bioprinting involving direct
      printing of cells and other biological substances for tissue reconstruction is
      still in its infancy. In this progress report, the current status of bioprinting
      in academia and industry is subjectively evaluated. The progress made is
      acknowledged, and the existing bottlenecks in bioprinting are discussed. Recent
      breakthroughs from a variety of associated fields, including mechanical
      engineering, robotic engineering, computing engineering, chemistry, material
      science, cellular biology, molecular biology, system control, and medicine may
      overcome some of these current bottlenecks. For this to happen, a convergence of
      these areas into a systemic research area "3D bioprinting" is needed to develop
      bioprinting as a viable approach for creating fully functional organs for
      standard clinical diagnosis and treatment including transplantation.

PMID- 29193880
TI  - Octyl ester of ginsenoside compound K as novel anti-hepatoma compound: Synthesis
      and evaluation on murine H22 cells in vitro and in vivo.
AB  - Ginsenoside compound K (M1) is the active form of major ginsenosides
      deglycosylated by intestinal bacteria after oral administration. However, M1 was
      reported to selectively accumulate in liver and transform to fatty acid esters.
      Ester of M1 was not excreted by bile as M1 was, which means it was accumulated in
      the liver longer than M1. This study reported a synthetic method of M1-O, a mono
      octyl ester of M1, and evaluated the anticancer property against murine H22 cell
      both in vitro and in vivo. As a result, both M1 and M1-O showed a dose-dependent
      manner in cytotoxicity assay in vitro. At lower dose of 12.5 MUm, M1-O showed
      moderate detoxification. Instead, M1-O exhibited significantly higher inhibition
      in H22-bearing mice than M1. M1-O induced murine H22 tumor cellular apoptosis in
      caspase-dependent pathway given that pan-caspase inhibitor, Z-VAD-FMK, could
      reverse the cytotoxicity induced by M1-O. Additionally, pro- and anti-apoptosis
      proteins, Bcl-2 and Bax, altered and consequently induced increased expression of
      cleaved caspase-3. Interestingly, cyclophosphamide regimen significantly induced
      atrophy of spleen and thymus, main immune organs, while M1-O treatment greatly
      alleviated this atrophy. Collectively, we propose M1-O as a candidate for live
      cancer treatment.

PMID- 29193881
TI  - Parent knowledge of disease management in cystic fibrosis: Assessing behavioral
      treatment management.
AB  - BACKGROUND: Cystic fibrosis (CF) is a life-shortening, burdensome disease
      requiring complex knowledge to manage the disease. Significant gaps in knowledge
      have been documented for parents, which may lead to unintentionally poor
      adherence and insufficient transfer of treatment responsibility from parents to
      adolescents. There are no current, validated measures of parent knowledge for
      this population and there are no measures that assess the knowledge required for
      day-to-day behavioral management of CF. We assessed the psychometric properties
      of the parent version of the Knowledge of Disease Management-Cystic Fibrosis
      measure (KDM-CF-P) using data from iCARE (I Change Adherence and Raise
      Expectations), a randomized control adherence intervention trial. METHODS: A
      total of 196 parents in the iCARE standard care/control arm completed 35 items
      assessing their knowledge of disease management at their 12-month study visit,
      prior to beginning the intervention. Items were eliminated from the measure if
      they met the threshold for ceiling effects, were deemed clinically irrelevant, or
      did not correlate well with their intended scale. Item-to-total correlations,
      confirmatory factor analysis, discriminant function, reliability, and convergent
      validity were calculated. RESULTS: The KDM-CF-P (19 items) demonstrated internal
      consistency of KR20 = 0.60 on each scale and a two-scale structure. Convergent
      validity for knowledge scores was found with maternal education, family income,
      and type of medical insurance. Parents correctly answered approximately 85% of
      items on the KDM-CF-P. CONCLUSIONS: The KDM-CF-P psychometrics support a two
      scale measure with clinical utility. It is useful for assessing gaps in knowledge
      that can be remediated through individualized, tailored interventions.

PMID- 29193882
TI  - Giant cell tumor of temporomandibular joint presenting as a parotid tumor:
      Challenges in the accurate subclassification of giant cell tumors in an unusual
      location.
AB  - Fine needle aspiration is frequently used as the initial diagnostic procedure in
      the work-up of head and neck lesions, including soft tissue masses and salivary
      gland neoplasms. Giant cell tumors (GCTs), both osseous and extraosseous, are
      benign tumors that occur, albeit rarely, in the head and neck region.
      Extraosseous GCTs may be further classified based on their tissue of origin and
      specific anatomic location. Regardless of location, giant cell tumors are
      morphologically similar and share cytologic and histologic diagnostic criteria.
      Evaluation of imaging is therefore essential to the correct classification of
      these tumors. Accurate diagnosis is crucial since the clinical behavior and
      treatment is significantly different among the subtypes of GCTs. The case
      presented herein illustrates the diagnostic dilemma between two uncommon entities
      in an unusual site: GCT of parotid gland and tenosynovial GCT.

PMID- 29193884
TI  - Morphological and clinical evaluation of prostatic urethra using modified
      sonourethrography with retrograde jelly injection.
AB  - OBJECTIVE: Using modified sonourethrography (mSUG) with retrograde jelly
      injection to precisely measure the morphological characteristics of the prostatic
      urethra, we assessed prostatic urethral morphology associated with clinical
      parameters of benign prostatic hyperplasia (BPH). METHODS: BPH patients (n = 43)
      and control patients with localized prostate cancer (PC; n = 57) were imaged by
      mSUG before surgery. Using the seminal colliculus as a landmark, prostatic
      urethral angulation (PUA), sagittal urethral diameter, and anterior or posterior
      prostatic urethral length were measured. The International Prostatic Symptoms
      Score (IPSS) was also evaluated in all patients. The Bladder Outlet Obstruction
      Index (BOOI) was measured in BPH patients that could void in a pressure-flow
      study. Parameters were compared between BPH and PC patients, and correlations
      among morphological and clinical parameters were evaluated. RESULTS: Prostatic
      urethras were clearly observed in all patients by mSUG. PUA, sagittal urethral
      diameter, and posterior urethral length were all greater in BPH than PC patients
      (P < .05). Among all parameters examined, PUA had the strongest correlation with
      IPSS (r = 0.56). Longitudinal urethral diameter showed the strongest correlation
      with BOOI, whereas PUA was not correlated with BOOI. CONCLUSIONS: Prostatic
      urethral morphology can be imaged precisely by mSUG. Morphometric measurements
      showed that increased PUA was strongly correlated with problematic urinary
      symptoms, and a flattened shape of the posterior urethra, such as extension of
      the sagittal urethral diameter, was correlated with urinary tract obstruction by
      BPH.

PMID- 29193885
TI  - AquaMMapS: An Alternative Tool to Monitor the Role of Water Molecules During
      Protein-Ligand Association.
AB  - Unquestionably, water appears to be an active player in the noncovalent protein
      ligand binding process, as it can either bridge interactions between protein and
      ligand or can be replaced by the bound ligand. Accordingly, in the last decade,
      alternative computational methodologies have been sought with the aim of
      predicting the position and thermodynamic profile of water molecules (i.e.,
      hydration sites) in the binding site using either the ligand-bound or ligand-free
      protein conformation. Herein, we present an alternative approach, named
      AquaMMapS, that provides a three-dimensional sampling of putative hydration
      sites. Interestingly, AquaMMapS can post-inspect molecular dynamics (MD)
      trajectories obtained from different MD engines using indifferently
      crystallographic or docking-driven structures as a starting point. Moreover,
      AquaMMapS is naturally integrated into supervised molecular dynamics (SuMD)
      simulations, presenting the possibility to inspect hydration sites during the
      ligand-protein association process. Finally, a penalty scoring method, named
      AquaMMapScoring(AMS), was developed to evaluate the number and nature of the
      water molecules displaced by a ligand approaching its binding site during the
      binding event, guiding a medicinal chemist to explore the most suitable regions
      of a ligand that can be decorated either with or without interfering with the
      interaction networks mediated by water molecules with specific recognition
      regions of the protein.

PMID- 29193883
TI  - Economic Evaluation of Lupus Nephritis in the Systemic Lupus International
      Collaborating Clinics Inception Cohort Using a Multistate Model Approach.
AB  - OBJECTIVE: Little is known about the long-term costs of lupus nephritis (LN). The
      costs were compared between patients with and without LN using multistate
      modeling. METHODS: Patients from 32 centers in 11 countries were enrolled in the
      Systemic Lupus International Collaborating Clinics inception cohort within 15
      months of diagnosis and provided annual data on renal function, hospitalizations,
      medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy
      or the American College of Rheumatology classification criteria. Renal function
      was assessed annually using the estimated glomerular filtration rate (GFR) or
      estimated proteinuria. A multistate model was used to predict 10-year cumulative
      costs by multiplying annual costs associated with each renal state by the
      expected state duration. RESULTS: A total of 1,545 patients participated; 89.3%
      were women, the mean +/- age at diagnosis was 35.2 +/- 13.4 years, 49% were
      white, and the mean followup duration was 6.3 +/- 3.3 years. LN developed in
      39.4% of these patients by the end of followup. Ten-year cumulative costs were
      greater in those with LN and an estimated glomerular filtration rate (GFR) <30
      ml/minute ($310,579 2015 Canadian dollars versus $19,987 if no LN and estimated
      GFR >60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus
      $20,499 if no LN and estimated proteinuria <0.25 gm/day). CONCLUSION: Patients
      with estimated GFR <30 ml/minute incurred 10-year costs 15-fold higher than those
      with normal estimated GFR. By estimating the expected duration in each renal
      state and incorporating associated annual costs, disease severity at presentation
      can be used to anticipate future health care costs. This is critical knowledge
      for cost-effectiveness evaluations of novel therapies.

PMID- 29193886
TI  - Association between severe nausea and vomiting in early pregnancy and the risk of
      neural tube defects in Northern China.
AB  - BACKGROUND: This study assessed the association between severe NVP and the risk
      of NTD in offspring compared with a population and a malformed control group. We
      also assessed whether folic acid supplements modified this association. STUDY
      DESIGN AND SETTING: A case-control study was conducted with subjects enrolled
      from June 19, 2002, to November 18, 2014, from a population-based birth defects
      surveillance system that monitors major external structural birth defects through
      active case ascertainment in Shanxi Province, China. The main comparison was
      between women with NTD-affected offspring who experienced NVP in early pregnancy
      versus those who did not. A multivariable logistic regression model was used to
      examine the associations between severe NVP and the risk of NTD while adjusting
      for potential confounding factors. The risk was estimated by calculating the odds
      ratio (OR) and 95% confidence intervals (CIs). RESULTS: The adjusted OR (AOR) of
      severe NVP for NTDs was 3.25 (95%CI 2.56, 4.12) compared with the population
      control, and 1.65 (95%CI 1.00, 2.72) compared with the malformed controls. When
      stratified by intake of folic acid supplements, the AOR for severe NVP was 3.40
      (95%CI 2.61, 4.42) in the non-intake of folic acid supplements stratum and 2.51
      (95%CI 1.42, 4.43) in the intake of folic acid supplements stratum. CONCLUSION:
      We conclude that severe NVP is associated with NTDs, and that severe NVP may be a
      consequence, rather than a cause, of NTDs.

PMID- 29193887
TI  - Systems Pharmacology of VEGF165b in Peripheral Artery Disease.
AB  - We built a whole-body computational model to study the role of the poorly
      understood vascular endothelial growth factor (VEGF)165b splice isoform in
      peripheral artery disease (PAD). This model was built and validated using
      published and new experimental data from cells, mice, and humans, and explicitly
      accounts for known properties of VEGF165b : lack of extracellular matrix (ECM)
      binding and weak phosphorylation of vascular endothelial growth factor receptor-2
      (VEGFR2) in vitro. The resulting model captures all known information about
      VEGF165b distribution and signaling in human PAD, and provides novel,
      nonintuitive insight into VEGF165b mechanism of action in vivo. Although VEGF165a
      and VEGF165b compete for VEGFR2 in vitro, simulations show that these isoforms do
      not compete for VEGFR2 at much lower physiological concentrations. Instead,
      reduced VEGF165a may drive impaired VEGFR2 signaling. The model predicts that
      VEGF165b does compete for binding to VEGFR1, supporting a VEGFR1-mediated
      response to anti-VEGF165b . The model predicts a key role for VEGF165b in PAD,
      but in a different way than previously hypothesized.

PMID- 29193888
TI  - Associations Between Slower Walking Speed and T1rho Magnetic Resonance Imaging of
      Femoral Cartilage Following Anterior Cruciate Ligament Reconstruction.
AB  - OBJECTIVE: To determine whether walking speed, collected at 6 and 12 months
      following anterior cruciate ligament reconstruction (ACLR), is associated with
      inter-extremity differences in proteoglycan density, measured via T1rho magnetic
      resonance imaging, in tibiofemoral articular cartilage 12 months following ACLR.
      METHODS: Twenty-one individuals with a unilateral patellar-tendon autograft ACLR
      (10 women and 11 men, mean +/- SD age 23.9 +/- 2.7 years, mean +/- SD body mass
      index 23.9 +/- 2.7 kg/m2 ) were recruited for participation in this study.
      Walking speed was collected using 3-dimensional motion capture at 6 and 12 months
      following ACLR. The articular cartilage of the medial femoral condyle (MFC) and
      lateral femoral condyle and medial and lateral tibial condyles was manually
      segmented and subsectioned into 3 regions of interest (anterior, central, and
      posterior) based on the location of the meniscus in the sagittal plane. Inter
      extremity mean T1rho relaxation time ratios (T1rho ACLR extremity / T1rho
      contralateral extremity) were calculated and used for analysis. Pearson product
      moment correlations were used to determine associations between walking speed and
      inter-extremity differences in T1rho relaxation time ratios. RESULTS: Slower
      walking speed 6 months post-ACLR was significantly associated with higher T1rho
      relaxation time ratios in the MFC of the ACLR extremity 12 months following ACLR
      (posterior MFC, r = -0.51, P = 0.02; central MFC, r = -0.47, P = 0.04).
      Similarly, slower walking speed at 12 months post-ACLR was significantly
      associated with higher T1rho relaxation time ratios in the posterior MFC ACLR
      extremity (r = -0.47, P = 0.04) 12 months following ACLR. CONCLUSION: Slower
      walking speed at 6 and 12 months following ACLR may be associated with early
      proteoglycan density changes in medial femoral compartment cartilage health in
      the first 12 months following ACLR.

PMID- 29193889
TI  - Cysticercosis and cytodiagnosis.

PMID- 29193891
TI  - A novel NR2E3 gene mutation in autosomal recessive retinitis pigmentosa with
      cystic maculopathy.

PMID- 29193890
TI  - Translational Biomedical Informatics and Pharmacometrics Approaches in the Drug
      Interactions Research.
AB  - Drug interaction is a leading cause of adverse drug events and a major obstacle
      for current clinical practice. Pharmacovigilance data mining, pharmacokinetic
      modeling, and text mining are computation and informatic tools on integrating
      drug interaction knowledge and generating drug interaction hypothesis. We provide
      a comprehensive overview of these translational biomedical informatics
      methodologies with related databases. We hope this review illustrates the
      complementary nature of these informatic approaches and facilitates the
      translational drug interaction research.

PMID- 29193892
TI  - Association of Defective Regulation of Autoreactive Interleukin-6-Producing
      Transitional B Lymphocytes With Disease in Patients With Systemic Sclerosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc) has the highest case-specific mortality of
      any rheumatic disease, and no effective therapy is available. A clear
      manifestation of SSc is the presence of autoantibodies. However, the origin of
      autoantibody-producing B lymphocytes, their mechanisms of activation and
      autoantibody production, and their role remain unclear. This study was undertaken
      to identify mechanisms that contribute to pathogenic B cell generation and
      involvement in SSc and to assess the altered distribution and function of B cells
      in SSc patients. METHODS: Multicolor flow cytometry was performed to determine B
      cell subset distribution, cytokine production, and tolerance induction in SSc
      patients and healthy controls. Cytokine production following stimulation of the
      cells ex vivo was determined by multiplex assay. RESULTS: A range of defects in B
      lymphocyte tolerance and cytokine production in SSc were noted. There was
      evidence of altered distribution of transitional B cell subsets, increased
      production of interleukin-6 (IL-6) and IL-8, and defective tolerance induction in
      SSc B cells. In addition, B cells from SSc patients had a reduced ability to
      produce IL-10 when stimulated through innate immune pathways. In contrast to
      healthy individuals, tolerance checkpoints in SSc patients failed to suppress the
      emergence of B cells that produce autoantibodies with specificity to the Scl-70
      antigen, which is strongly associated with SSc. These defects were paralleled by
      altered intracellular signaling and apoptosis following B cell receptor
      engagement. CONCLUSION: Our findings provide new insights into mechanisms
      underlying defective B lymphocyte responses in patients with SSc and their
      contribution to disease.

PMID- 29193893
TI  - Sex Differences in Health Care Utilization, End-Stage Renal Disease, and
      Mortality Among Medicaid Beneficiaries With Incident Lupus Nephritis.
AB  - OBJECTIVE: While systemic lupus erythematosus and lupus nephritis (LN)
      disproportionately affect females, previous studies suggest that males may
      experience poorer outcomes. We undertook this study to investigate sex
      differences in health care utilization, end-stage renal disease (ESRD), and
      mortality among patients with LN receiving Medicaid, public insurance for low
      income individuals. METHODS: Within the Medicaid Analytic eXtract (MAX) from 29
      states (from 2000 to 2010), we used billing claims to identify individuals ages 5
      65 years with incident LN (positive predictive value 80%). MAX data were linked
      to the US Renal Data System to determine ESRD and to Social Security Death Index
      files to determine death. We estimated adjusted incidence rate ratios (IRRs) by
      sex for health care utilization using Poisson regression, and we used
      multivariable proportional hazards models to compare risks of ESRD and death by
      sex. RESULTS: Of 2,750 patients with incident LN, 283 (10%) were male. The mean
      +/- SD follow-up period for both sexes was 3.1 +/- 2.3 years. The mean +/- SD age
      was 29.6 +/- 13.9 years among females and 24.7 +/- 14.1 years among males (P <
      0.01). Males had fewer outpatient visits (IRR 0.88 [95% confidence interval (95%
      CI) 0.80-0.97]) and fewer emergency department visits (IRR 0.75 [95% CI 0.63
      0.90]). The 5-year cumulative incidence of ESRD was 22.3% in males and 21.2% in
      females. The 5-year cumulative incidence of death was 9.4% in males and 9.8% in
      females. Comparing males to females, there were no sex differences in ESRD
      (subdistribution hazard ratio [HR] 1.05 [95% CI 0.76-1.45]) or death (HR 0.81
      [95% CI 0.47-1.35]). CONCLUSION: In this cohort of patients with incident LN,
      ESRD and mortality were extremely high overall but were not increased among males
      compared to females. In this vulnerable population, biologic and health care
      utilization differences by sex may not significantly affect outcomes.

PMID- 29193894
TI  - Phenotypic and genotypic comparison of salmonellae from diarrhoeic and healthy
      humans and cattle, Nigeria.
AB  - The sources and modes of transmission of non-typhoidal Salmonella particularly
      zoonotic transmission are poorly understood in Africa. This study compared
      phenotypic and genotypic characteristics of Salmonellae isolated from cattle and
      humans. Faecal samples of diarrhoeic patients (n = 234), and a healthy population
      (n = 160), beef cattle at slaughter (n = 250), farms (n = 72) and market (n =
      100) were cultured for salmonellae and serotyping and antimicrobial
      susceptibility were determined. Whole-genome sequence typing (WGST) of selected
      isolates and bioinformatic analysis were used to identify the multilocus sequence
      type (MLST), plasmid replicons, antimicrobial resistance genes and genetic
      relatedness by single nucleotide polymorphism (SNP) analysis. The Salmonella
      isolates, diarrhoeic patients (n = 17), healthy population (n = 13), cattle
      (abattoir, n = 67; farms, n = 10; market n = 5), revealed 49 serovars; some
      serovars were common to humans and cattle. Rare serovars were prevalent:
      Colindale (cattle and humans); Rubislaw and Bredeney (humans); and Dublin, Give,
      Eastbourne, Hadar, Marseille, Sundsvall, Bergen, Ekotedo, Carno and Ealing
      (cattle). The sequence types (ST) include ST 584, ST 198, ST 562 and ST 512 for
      S. Colindale, S. Kentucky S. Rubislaw and S. Urbana, respectively. Clonal cluster
      shared by cattle and human WGST isolates was not found. Antimicrobial resistance
      rates were generally low and towards only chloramphenicol, ampicillin,
      gentamicin, ciprofloxacin, tetracycline and streptomycin, range 2.7%
      (chloramphenicol) to 8.9% (streptomycin). Multiply resistant isolates included
      serovars Kentucky, 4,5,12:i:- and Typhimurium. The study presents a baseline
      description of the prevalence, serotypes, antimicrobial resistance phenotypes and
      genetic relatedness of Salmonella isolated from healthy and diarrhoeic humans,
      and cattle at harvest, on farm and at market. Cattle are a reservoir of diverse
      salmonellae with shared serovars with humans, but WGST does not support zoonotic
      transmission. Further study with larger samples is recommended to determine
      whether epidemiological link exists between cattle and humans.

PMID- 29193895
TI  - Inflammatory Cytokines Stabilize SOXC Transcription Factors to Mediate the
      Transformation of Fibroblast-Like Synoviocytes in Arthritic Disease.
AB  - OBJECTIVE: Fibroblast-like synoviocytes (FLS) produce key synovial fluid and
      tissue components to ensure joint integrity under healthy conditions, whereas
      they become cancer-like and aggressively contribute to joint degeneration in
      inflammatory arthritis. The aim of this study was to determine whether the SOXC
      transcription factors SOX4 and SOX11, whose functions are critical in joint
      development and many cancer types, contribute to FLS activities under normal and
      inflammatory conditions. METHODS: We inactivated the SOXC genes in FLS from adult
      mice and studied the effect on joint homeostasis and tumor necrosis factor (TNF)
      induced arthritis. We used primary cells and synovial biopsy specimens from
      arthritis patients to analyze the interactions between inflammatory signals and
      SOXC proteins. RESULTS: Postnatal inactivation of the SOXC genes had no major
      effect on joint integrity in otherwise healthy mice. However, it hampered
      synovial hyperplasia and joint degeneration in transgenic mice expressing human
      TNF. These effects were explained by the ability of SOX4/11 to amplify the
      pathogenic impact of TNF on FLS by increasing their survival and migration. SOXC
      RNA levels were not changed by TNF and other proinflammatory cytokines, but SOXC
      proteins were strongly stabilized and able to potentiate the TNF-induced up
      regulation of genes involved in FLS transformation. Substantiating the relevance
      of these findings in human disease, SOXC protein levels, but not RNA levels, were
      significantly higher in inflamed synovium than in noninflamed synovium from
      arthritis patients. CONCLUSION: SOXC proteins are targets and pivotal mediators
      of proinflammatory cytokines during FLS transformation in arthritic diseases.
      Targeting of these proteins could thus improve current strategies to treat
      arthritic diseases and possibly other inflammatory diseases.

PMID- 29193897
TI  - Multilineage Constructs for Scaffold-Based Tissue Engineering: A Review of Tissue
      Specific Challenges.
AB  - There is a growing interest in the regeneration of tissue in interfacial regions,
      where biological, physical, and chemical attributes vary across tissue type. The
      simultaneous use of distinct cell lineages can help in developing in vitro
      structures, analogous to native composite tissues. This literature review gathers
      the recent reports that have investigated multiple cell types of various sources
      and lineages in a coculture system for tissue-engineered constructs. Such studies
      aim at mimicking the native organization of tissues and their interfaces, and/or
      to improve the development of complex tissue substitutes. This paper thus
      distinguishes itself from those focusing on technical aspects of coculturing for
      a single specific tissue. The first part of this review is dedicated to variables
      of cocultured tissue engineering such as scaffold, cells, and in vitro culture
      environment. Next, tissue-specific coculture methods and approaches are covered
      for the most studied tissues. Finally, cross-analysis is performed to highlight
      emerging trends in coculture principles and to discuss how tissue-specific
      challenges can inspire new approaches for regeneration of different interfaces to
      improve the outcomes of various tissue engineering strategies.

PMID- 29193898
TI  - Reporting from 8th International Congress on Peer Review and Scientific
      Publication: Challenges and opportunities for China's periodical and press
      industries.

PMID- 29193896
TI  - In utero ultrasound diagnosis of corpus callosum agenesis leading to the
      identification of orofaciodigital type 1 syndrome in female fetuses.
AB  - BACKGROUND: OFD1 syndrome is a rare ciliopathy inherited on a dominant X-linked
      mode, typically lethal in males in the first or second trimester of pregnancy. It
      is characterized by oral cavity and digital anomalies possibly associated with
      cerebral and renal signs. Its prevalence is between 1/250,000 and 1/50,000
      births. It is due to heterozygous mutations of OFD1 and mutations are often de
      novo (75%). Familial forms show highly variable phenotypic expression. OFD1
      encodes a protein involved in centriole growth, distal appendix formation, and
      ciliogenesis. CASES: We report the investigation of three female fetuses in which
      corpus callosum agenesis was detected by ultrasound during the second trimester
      of pregnancy. In all three fetuses, fetopathological examination allowed the
      diagnosis of OFD1 syndrome, which was confirmed by molecular analysis.
      CONCLUSIONS: To our knowledge, these are the first case reports of antenatal
      diagnosis of OFD1 syndrome in the absence of familial history, revealed following
      detection of agenesis of the corpus callosum. They highlight the impact of fetal
      examination following termination of pregnancy for brain malformations. They also
      highlight the contribution of ciliary genes to corpus callosum development.

PMID- 29193899
TI  - Role of Cochrane Reviews in informing US private payers' policies.
AB  - AIM: To assess the use of Cochrane Reviews to inform the medical policy documents
      of major US private payers. METHODS: The publically available drug policy
      documents of the five major US private payers (covering about 50% market) namely:
      Anthem, Aetna, Cigna, Humana and United Healthcare (UHC) were assessed in
      February 2017 and reviewed to find whether they had used Cochrane Reviews. We
      extracted information such as use of Cochrane Reviews, number of Cochrane Reviews
      used, context of use and impact of Cochrane Reviews on policy, and Cochrane
      Review Group (CRG) and Cochrane Center linked to the Cochrane Review. RESULT:
      Among the selected payers, less than half of the policy documents used Cochrane
      Reviews: maximum for Aetna (52%) and minimum for Humana (2%). Three hundred and
      sixty-one Cochrane Reviews from 42 CRGs have been used to inform 118 drug policy
      documents: Aetna (221) Anthem (64), Cigna (30), and UHC (25). The highest number
      of reviews used from any Cochrane Center was 79 (UK). The most reviews used from
      any CRG were 27 (Musculoskeletal Group). The most reviews used to inform any one
      policy was 18 (Drug: Botulinum Toxin, Payer: Aetna). Overall, 66% of the Cochrane
      Reviews were used to inform the background section of the policy document and 34%
      supported the clinical usage of the drug. Furthermore, 42% of the reviews had
      cited inline in the policies they were used to inform. CONCLUSION: Cochrane
      Reviews are used to inform the US healthcare payers' policies, but there is still
      scope to encourage the further usage of Cochrane Reviews in healthcare decision
      making.

PMID- 29193900
TI  - ERRATUM.

PMID- 29193901
TI  - Hepatitis C virus infection and risk of gallstones: A meta-analysis.
AB  - BACKGROUND/OBJECTIVES: Gallstones and its complications are one of the most
      common hepatobiliary tract diseases. Several epidemiologic studies have suggested
      that patients with hepatitis C virus (HCV) infection might be at an increased
      risk of gallstones. However, the data on this relationship remain inconclusive.
      This meta-analysis was conducted with the aims to summarize all available
      evidence. METHODS: A literature search was performed using MEDLINE and EMBASE
      databases from inception to May 2016. Studies that reported relative risks, odd
      ratios, or hazard ratios comparing the risk of gallstones among HCV-infected
      patients versus subjects without HCV infection were included. Pooled odds ratio
      (OR) and 95% confidence interval (CI) were calculated using a random-effect,
      generic inverse variance method. RESULTS: Eleven studies met our eligibility
      criteria and were included in the analysis. The pooled OR of gallstones in HCV
      infected patients versus subjects without HCV infection was 1.83 (95% CI, 1.35 to
      2.48, I2  = 89%). Subgroup analysis showed that significant risk was increased
      for both male (pooled OR of 2.07, 95% CI, 1.14 to 3.76) and female (pooled OR of
      3.00, 95% CI, 2.16 to 4.17). CONCLUSIONS: Our study demonstrated a significantly
      increased risk of gallstones among HCV-infected patients. Further studies are
      required to clarify how this risk should be addressed in the clinical picture.

PMID- 29193902
TI  - Bispecific antibody process development: Assembly and purification of knob and
      hole bispecific antibodies.
AB  - Production of knob and hole dual light chain bispecific antibodies poses several
      unique challenges for development of a feasible industrial scale manufacturing
      process. We developed an efficient process for the assembly and purification of
      knob and hole dual light chain bispecific antibodies. Two distinct half
      antibodies targeting two different antigens were expressed separately in
      Escherichia coli cells and captured independently using Protein A chromatography.
      When combined, the knob and hole mutations in the CH3 domains promoted
      heterodimer formation. The hinge region disulfides were reduced and reoxidized to
      form the disulfide bridge between the two complementary half antibodies.
      Unreacted half antibodies, noncovalently linked homodimers, covalently linked
      homodimers, and noncovalently linked heterodimers are impurities closely related
      to the product of interest and are challenging to remove by standard processes.
      Characterization of the molecular properties of the half antibodies and high
      throughput screening predicted column chromatography performance and allowed for
      rapid development of downstream purification steps for removal of unique product
      related and process-related impurities. (c) 2018 American Institute of Chemical
      Engineers Biotechnol. Prog., 34:397-404, 2018.

PMID- 29193903
TI  - Genetic susceptibility to thalidomide embryopathy in humans: Study of candidate
      development genes.
AB  - Thalidomide is a drug used worldwide for several indications, but the molecular
      mechanisms of its teratogenic property are not fully understood. Studies in
      animal models suggest the oxidative stress, the inhibition of angiogenesis, and
      the binding to E3-ubiquitin ligase complex as mechanisms by which thalidomide can
      change the expression of genes important to embryonic development. In this study,
      seven polymorphisms in genes related to development (FGF8, FGF10, BMP4, SHH,
      TP53, TP63, and TP73) were analyzed in people with thalidomide embryopathy (TE)
      and compared to people without malformations. The sample consisted of 36 people
      with TE and 135 unrelated and nonsyndromic people who had their DNA genotyped by
      PCR real-time. Although no allelic or genotypic differences were observed between
      the groups, we hypothesized that other regions in these genes and related genes
      may play an important role in thalidomide teratogenesis, which is known to have a
      genetic contribution. Identifying such molecular mechanisms is essential for the
      development of a molecule that will be analogue to thalidomide but safe enough to
      avoid the emergence of new cases of TE.

PMID- 29193904
TI  - Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and
      peripheral blood cells observed in a Fanconi anemia patient leads to milder
      phenotype.
AB  - BACKGROUND: Fanconi anemia (FA) is a rare disorder characterized by congenital
      malformations, progressive bone marrow failure, and predisposition to cancer.
      Patients harboring X-linked FANCB pathogenic variants usually present with severe
      congenital malformations resembling VACTERL syndrome with hydrocephalus. METHODS:
      We employed the diepoxybutane (DEB) test for FA diagnosis, arrayCGH for detection
      of duplication, targeted capture and next-gen sequencing for defining the
      duplication breakpoint, PacBio sequencing of full-length FANCB aberrant
      transcript, FANCD2 ubiquitination and foci formation assays for the evaluation of
      FANCB protein function by viral transduction of FANCB-null cells with lentiviral
      FANCB WT and mutant expression constructs, and droplet digital PCR for
      quantitation of the duplication in the genomic DNA and cDNA. RESULTS: We describe
      here an FA-B patient with a mild phenotype. The DEB diagnostic test for FA
      revealed somatic mosaicism. We identified a 9154 bp intragenic duplication in
      FANCB, covering the first coding exon 3 and the flanking regions. A four bp
      homology (GTAG) present at both ends of the breakpoint is consistent with
      microhomology-mediated duplication mechanism. The duplicated allele gives rise to
      an aberrant transcript containing exon 3 duplication, predicted to introduce a
      stop codon in FANCB protein (p.A319*). Duplication levels in the peripheral blood
      DNA declined from 93% to 7.9% in the span of eleven years. Moreover, the patient
      fibroblasts have shown 8% of wild-type (WT) allele and his carrier mother showed
      higher than expected levels of WT allele (79% vs. 50%) in peripheral blood,
      suggesting that the duplication was highly unstable. CONCLUSION: Unlike sequence
      point variants, intragenic duplications are difficult to precisely define,
      accurately quantify, and may be very unstable, challenging the proper diagnosis.
      The reversion of genomic duplication to the WT allele results in somatic
      mosaicism and may explain the relatively milder phenotype displayed by the FA-B
      patient described here.

PMID- 29193906
TI  - Detection of Sotatercept (ACE-011) in human serum by SAR-PAGE and western single
      blotting.
AB  - A method for the detection of Sotatercept (ACE-011, ACVR2A-Fc) in human serum is
      presented. The method is a modification of a recently published protocol for
      Luspatercept (ACE-536, ACVR2B-Fc), another erythropoiesis stimulating fusion
      protein. Out of 27 tested antibodies against either the extracellular domain of
      ACVR2A or the full-length protein, only 4 antibodies bound strongly enough to
      Sotatercept for usage with immunoprecipitation followed by SAR-PAGE and Western
      single blotting. The adapted protocol allows the detection of 0.1 ng/mL
      Sotatercept in just 50 MUL human serum. None of the 3 commercial ACVR2-ELISAs was
      able to detect Sotatercept and the 2 tested surrogate proteins, even in the
      MUg/mL range. As for Luspatercept, only IPG-IEF/2D-PAGE generated discrete
      isoforms. Due to the long serum half-life, the SAR-PAGE method will be able to
      detect Sotatercept for several weeks and will be very useful in doping testing.

PMID- 29193905
TI  - Circulating myomiRs: a new class of biomarkers to monitor skeletal muscle in
      physiology and medicine.
AB  - MicroRNAs (miRNA) are small non-coding RNAs that target mRNAs and are
      consequently involved in the post-transcriptional regulation of gene expression.
      Some miRNAs are ubiquitously expressed in tissue, while others are tissue
      specific or tissue-enriched. miRNAs can be released by cells and are found in
      various biofluids, including serum and plasma. Thus, measuring miRNAs in the
      circulation may provide information on the originating tissue or cells. MyomiRs
      are described as striated muscle-specific or muscle-enriched miRNAs. Their
      circulating levels can be measured and have been proposed to be new biomarkers of
      physiological and pathological muscle processes. The aims of this review are to
      summarize the current knowledge of circulating myomiRs, to identify the types of
      information they can provide about skeletal muscle, and to determine how to apply
      that information in the fields of research and medicine.

PMID- 29193907
TI  - Tuberculosis in Pap samples with emphasis on LBC: Caught only when thought.
AB  - Despite being a commonly encountered infection, the clinical diagnosis of
      tuberculosis of the uterine cervix is elusive. Though a straightforward diagnosis
      on tissue sections, identification of typical features of tubercular infection on
      cervical Pap samples is challenging. In our experience, the infrequent pale
      staining collections of epithelioid cells are difficult to pick up on Pap stained
      smears, particularly LBC samples. In this series, 2 of the three samples were
      reported as atypical squamous cells of undetermined significance while 1 was
      reported as inflammatory at the initial diagnosis. Scattered Langhans' type giant
      cells may be seen as a subtle clue which should prompt the search for epithelioid
      cell granulomas. These cases may have a mass lesion clinically while no obvious
      signs of malignancy on the cervical samples.

PMID- 29193908
TI  - A detailed characterization of congenital defects and mortality following
      moderate X-ray doses during neurulation.
AB  - BACKGROUND: Both epidemiological and animal studies have previously indicated a
      link between in utero radiation exposure and birth defects such as
      microphthalmos, anophthalmos, and exencephaly. However, detailed knowledge on
      embryonic radiosensitivity during different stages of neurulation is limited,
      especially in terms of neural tube defect and eye defect development. METHODS: To
      assess the most radiosensitive stage during neurulation, pregnant C57BL6/J mice
      were X-irradiated (0.5 Gy or 1.0 Gy) at embryonic days (E)7, E7.5, E8, E8.5, or
      E9. Next, the fetuses were scored macroscopically for various defects and
      prenatal resorptions/deaths were counted. In addition, cranial skeletal
      development was ascertained using the alcian-alizarin method. Furthermore,
      postnatal/young adult survival was followed until 5 weeks (W5) of age, after X
      irradiation at E7.5 (0.1 Gy, 0.5 Gy, or 1.0 Gy). In addition, body and brain
      weights were registered at adult age (W10) following X-ray exposure at E7.5 (0.1
      Gy, 0.5 Gy). RESULTS: Several malformations, including microphthalmos and
      exencephaly, were most evident after irradiation at E7.5, with significance
      starting respectively at 0.5 Gy and 1.0 Gy. Prenatal mortality and weight were
      significantly affected in all irradiated groups. Long-term follow-up of E7.5
      irradiated animals revealed a reduction in survival at 5 weeks of age after high
      dose exposure (1.0 Gy), while lower doses (0.5 Gy, 0.1 Gy) did not affect brain
      and body weight at postnatal week 10. CONCLUSIONS: With this study, we gained
      more insight in radiosensitivity throughout neurulation, and offered a better
      defined model to further study radiation-induced malformations and the underlying
      mechanisms.

PMID- 29193909
TI  - Controlling Protein Adsorption through Nanostructured Polymeric Surfaces.
AB  - The initial host response to healthcare materials' surfaces after implantation is
      the adsorption of proteins from blood and interstitial fluids. This adsorbed
      protein layer modulates the biological/cellular responses to healthcare
      materials. This stresses the significance of the surface protein assembly for the
      biocompatibility and functionality of biomaterials and necessitates a profound
      fundamental understanding of the capability to control protein-surface
      interactions. This review, therefore, addresses this by systematically analyzing
      and discussing strategies to control protein adsorption on polymeric healthcare
      materials through the introduction of specific surface nanostructures. Relevant
      proteins, healthcare materials' surface properties, clinical applications of
      polymer healthcare materials, fabrication methods for nanostructured polymer
      surfaces, amorphous, semicrystalline and block copolymers are considered with a
      special emphasis on the topographical control of protein adsorption. The review
      shows that nanostructured polymer surfaces are powerful tools to control the
      amount, orientation, and order of adsorbed protein layers. It also shows that the
      understanding of the biological responses to such ordered protein adsorption is
      still in its infancy, yet it has immense potential for future healthcare
      materials. The review, which is-as far as it is known-the first one discussing
      protein adsorption on nanostructured polymer surfaces, concludes with
      highlighting important current research questions.

PMID- 29193910
TI  - Does noninvasive follicular thyroid neoplasm with papillary-like nuclear features
      have distinctive features on sonography?
AB  - BACKGROUND: The noninvasive encapsulated follicular variant of papillary
      carcinoma (nEFVPTC) has recently been reclassified to "noninvasive follicular
      thyroid neoplasm with papillary-like nuclear features (NIFTP)," removing this
      entity from the malignant category. This re-categorization has had major
      implications for clinical management. NIFTP has overlapping cytohistologic
      features with papillary thyroid carcinoma (PTC) and with follicular adenomas
      (FA), but sonographic data comparing NIFTP to PTC and FA is lacking. Our study
      examines the sonographic features of NIFTP as compared with PTC and FA. METHODS:
      Ultrasound scans and Doppler blood flow from subjects who had pre-surgical
      sonograms and fine needle aspiration biopsies with final surgical pathology
      diagnoses of NIFTP/nEFVPTC, classical PTC, and FA between 01/2013-08/2016 were
      assessed. Sonographic and Doppler features as well as Bethesda System (TBS)
      diagnoses were recorded and analyzed. RESULTS: 40 NIFTP, 58 classical PTC, and 23
      FA cases were included. The most common NIFTP pre-surgical TBS cytology diagnosis
      was Atypia of Undetermined Significance (AUS/FLUS) (40%). NIFTP cases
      predominantly displayed wider-than-tall shape (100%), smooth borders (75%),
      occurrence in multinodular glands (82.5%), heterogeneous echogenicity (50%), both
      perinodular and intranodular Doppler flow patterns (70%), minimal Doppler flow
      grade (62.5%), and no calcifications (90%). CONCLUSIONS: Our study demonstrates
      that NIFTP, PTC, and FA display several distinguishing and overlapping
      sonographic and Doppler features. Sonographic features appear to complement
      cytology findings and may help raise pre-operative concern for NIFTP in the
      proper clinical setting, potentially leading to a more conservative management
      approach.

PMID- 29193911
TI  - Bacterial Species, Susceptibility to antibiotics and characteristics of patients
      with surgicalsite infections.
AB  - Surgical site infections (SSI) are the most common healthcare
      associatedinfections. Approximately 2-5% of all surgeries develop SSI as a
      complication.These infections are responsible for significant fatality,
      morbidity, andlength of hospital stay. The purpose of this study was to describe
      characteristicsof SSI in a community hospital in Puerto Rico. This was cross
      sectionalstudy. Between July 2013 and August 2015, 5468 major operativeprocedures
      were performed and 31 SSI were reported for an overall SSIincidence rate of
      0.57%. A total of 31 cases of SSI were studied. The meanage of patients was 59.4
      years, with a range of to 29 to 89 years. The medianage was 64 years. The sex
      distribution showed 22 women (71%) and 9 men(29%). The prevalence rate of
      diabetes mellitus was 13/31 (42%). In thisstudy 90% of patients with SSI had at
      least one underlying health condition(diabetes, hypertension, obesity, age > 65
      years). Location of surgicalsite infections were: abdominal 16 (52%), orthopedic
      4 (13%), pelvic 7(22%), stump 3 (10%), and chest tube 1 (3%). A total of 12
      different bacterialpathogens were found. A single etiologic agent was identified
      in 18 patients(53%) and multiple agents were found in 13 patients (47%).
      Enterococcusfaecalis was the most common pathogen (45% of patients) followedby
      Escherichia coli (39% of patients). The majority of bacteria isolated
      fromcultures were susceptible to B-lactams and aminoglycosides.

PMID- 29193912
TI  - Bilateral Tibia Fibrous Dysplasia in a Pediatric Patient Treated with
      Intramedullary Nailing: A Case Report.
AB  - Fibrous dysplasia is benign developmental disorders of bone where normallamellar
      cancellous bone is replaced with immature fibro-osseus tissue resultingin poorly
      formed trabeculae of immature woven bone. It may affectone (monostotic) or
      multiple bones (polyostotic). Polyostotic disease is lesscommon, 20-25% of
      patients, mostly in children below 10 years old andtends to enlarge beyond bone
      maturation ration which can cause pain, progressivedamage and higher tendency of
      pathological fractures.(1) We reporta case of polyostotic fibrous dysplasia
      present on bilateral tibia diaphysis. Patientpresented with bilateral leg pain on
      examination and imaging showedbilateral tibia lytic lesion. Management consisted
      of reaming and intramedullarynailing on bilateral tibia after which patient
      presented without painand radiographs showing no evidence of lesion. Tibia x-rays
      demonstrated exuberantcortical intramedullary bone formation with disappearance
      of thescalloped osteolytic lesions on the inner wall of tibial cortex. Clinically
      the patient'ssymptoms disappeared giving the opportunity to return to contact
      sportswithout limitation.

PMID- 29193913
TI  - A Broken Heart: Takotsubo Cardiomyopathy.
AB  - This case illustrates the unusual presentation of Takotsubo cardiomyopathy inan
      elderly male patient with characteristic chest pain and dyspnea associatedwith
      electrocardiographic changes of biphasic T wave inversions and QT
      intervalprolongation on anterior segment, mimicking acute coronary
      syndrome.Takotsubo cardiomyopathy is a transient systolic dysfunction of the
      apicaland/or mid and anterior segments of left ventricle most frequently seen in
      post-menopausal women, up to 80 to 100% of cases. Often there is a history of a
      recent(within the previous two months) episode of severe emotional or
      physicalstress associated with the event.

PMID- 29193914
TI  - Secondary Resistance to dopamine agonist after thirteen months of successful
      treatmentin a 42 years old man.
AB  - Prolactinomas are the most common hormone-secreting pituitary tumorsand
      represents approximately 40% of all pituitary adenomas. Pharmacologytherapy with
      dopamine agonists is the mainstay treatment for prolactinomasUsually, patients
      respond to these drugs with decreased level of the serumprolactin and with time,
      by tumor shrinkage. Less than 10% of patientswith prolactinomas exhibit
      resistance to the action of dopamine agonists, asdefined by the lack of
      normalization of the serum prolactin levels despite long-term treatment at high
      doses of these drugs. However secondary resistanceto dopamine agonists therapy
      has also been described in patients who wereinitially responsive to treatment,
      either with Cabergoline or Bromocriptinebut later develop dopamine agonist
      resistance, with elevated prolactin levelsand sometimes an enlarging tumor volume
      several years afterwards. Wereport a case of a male patient with prolactinoma who
      developed drug resistance13 months after initial dopamine agonist therapy.

PMID- 29193915
TI  - Cervical cancer screening in Brazil according to economic income.

PMID- 29193916
TI  - Choledochal Cyst: Hepaticoduodenostomy or hepaticojejunostomy?
AB  - Choledochal cysts are cystic dilatation of the common bile duct managed
      byexcision and hepatico-intestinal reconstruction. The gold standard after
      choledochalcyst excision is reconstruction using the jejunum. With the advent
      oflaparoscopy the pendulum has changed toward hepaticoduodenostomy
      reconstruction.We review the classification, diagnosis and recent management
      ofcholedochal cyst.

PMID- 29193917
TI  - Clinical profile, bacterial isolates, and antibiotic resistance of corneal ulcers
      in Puerto Rico.

PMID- 29193918
TI  - Compliance with management guidelines in patients with suspected dengue.
AB  - Dengue is an endemic disease in Puerto Rico, with three to nine thousandsuspected
      dengue cases reported yearly. In PR, physicians are required to maintainmedical
      education courses about dengue in order to recertify their medicallicenses. The
      purpose of this study was to describe characteristics of patientsadmitted to
      Bella Vista Hospital with suspected dengue and estimate thecompliance with
      guidelines established by the CDC documented in medical records.A total of 197
      medical records of patients admitted with diagnosis of suspecteddengue during
      January 1, 2013 through December 31, 2013 were reviewed.The annual distribution
      of admitted cases showed a higher incidenceduring the months of June through
      September, with August having the higherincidence of all. Combined aches and
      pains were most commonly reported atadmission with a prevalence of 82%. In
      general there was a low prevalence ofsevere disease as per definition at
      presentation (DM, clinical fluid accumulation,hepatomegaly, pregnancy and/or
      renal insufficiency). Overall, compliancewith CDC established guidelines were
      only partially followed. The guidelinethat was followed more frequently was a
      daily CBC, with 95% of patientshaving this as part of their management.
      Prevalence of administration ofisotonic intravenous fluids was 63%, monitoring of
      vital signs was 48%),and administration of bolus of intravenous fluid was11%. No
      fatalities werereported during the period.

PMID- 29193919
TI  - Diabetes Treatment Satisfaction Questionnaire (DTSQ) of in non-ambulatory type 2
      diabetic patients.
AB  - OBJECTIVES: The aim of this work is to determine the diabetes treatment
      satisfactionin a group of hospitalized patients with type 2 diabetes. METHODS:
      observational cross research. Patients over the age of 18with diagnosed type 2
      diabetes of at least one year until the present studywere included. Those
      presenting pathologies attributed to diabetes wereexcluded. Patients should have
      responded to the DTSQ questionnaireupon admission. r Pearson regression,
      multivariate linear regressionand U Mann-Whitney tests were analyzed. RESULTS: A
      total of 102 patients were included with an average age of 63.1years. Average
      value of the DTSQs was 14.5.A significant statistic correlation was observed
      between the score of thequestionnaires and good diabetes control showed by the
      levels of HbAc1and fasting blood glucose, among other parameters. Indeed there
      wasno correlation between satisfaction and age and BMI. Women had
      lowersatisfaction score than men. CONCLUSIONS: levels of diabetes treatment
      satisfaction in the study populationcorrelated well with diabetic status. That
      is, the lower diabeticcompromise, the better satisfaction score. The degree of
      satisfaction inpatients with type 2 diabetes was lower than the observed on
      patients withthe same pathology but from primary levels of health care.

PMID- 29193920
TI  - High Output Cardiac Failure in a Patient Presenting with Acute Myeloid Leukemia
      and Leukostasis.
AB  - In this case report a patient presents with high-output cardiac failure in the
      clinicalsetting of acute leukemia and leukostasis. Case particulars are
      presented, literatureis reviewed and a potential mechanistic explanation is
      proposed to describepresentation and clinical findings.

PMID- 29193921
TI  - An Isolated Gluteus Minimus Tendon Tear with Stress Fracture of the Iliac Wing in
      a Marathon Runner:A case report.
AB  - Stress fractures and muscle strains are common in marathon runners. Moststress
      fractures occur in lower extremities and tibia stress fractures comprisealmost
      half. Iliac wing stress fractures are not commonly found in runners andare
      usually related to osteoporosis. There have been 4 previous reports of iliac
      stressfractures in marathon runners none reported an associated isolated
      gluteusminimus tendon tears. We will report a case of a female marathon runner
      withiliac wing stress fracture with associated isolated gluteus minimus tendon
      tear.

PMID- 29193922
TI  - Implementation of a pre-operative decolonization protocol of Methicillin
      Resistance Staphylococcusaureus in elective orthopedic surgery at Manati Medical
      Center: Pilot Study.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a strain of S. aureus
      thatshows resistance to multiple antibiotics. Up to 30% of S. aureus strains
      isolatedfrom nosocomial infections are MRSA, and it has become a growing
      problemfor public health. The cost of MRSA infection is also having a huge
      impactfinancially and results in considerable resource utilization. Puerto
      Rico'sLegislature passed Law # 298 on October 19, 2012 for the control and
      preventionof MRSA infections in medical installations in Puerto Rico. In order to
      complywith the law we conducted a pilot study to identify possible setbacks of
      theimplementation of the MRSA decolonization protocol as standard of care therapy
      inour institution while contributing to the process of quality improvement
      andpatient safety. Nasal swabs were taken at the Pre-admission Department
      andprocessed through a PCR-based MRSA detection assay. A protocol of
      decolonizationin patients with positive results was implemented. The study
      showedthat patients without apparent risk factors could be colonized either
      withMRSA or Methicillin-sensitive S. aureus (MSSA). The time between pre
      admission and surgery was less than the indicated for a proper
      decolonizationprocedure. Therefore, 50% of the scheduled surgeries could have
      beenpostponed in case of positive MRSA or MSSA. In our experience patient's
      educationwas crucial to guarantee compliance and adherence to treatment. Inorder
      to decrease risk of wound infection we recommend that both, screeningprocess and
      decolonization if required, be performed before the preadmissionappointment for
      elective surgery. This study provided a framework for MRSApre-admission screening
      and decolonization in our Institution.

PMID- 29193923
TI  - Intradialytic Hypertension / Hypotension and Mortality in San Juan, Puerto Rico.
AB  - End Stage Renal Disease patients undergo profound hemodynamic changesduring
      hemodialysis treatments which are now recognized as a marker forincreased risk of
      morbidity and mortality. Development of intradialytichypotension or hypertension
      are a common clinical problem in this populationwith an incidence of up to 20%.
      We performed a retrospective review of49 Hispanic patients receiving ambulatory
      hemodialysis during a period of6 months to ascertain the development of
      aforementioned intradialytic events.Clinical data examined the association of
      these events to mortality and theirrelationship to antihypertensive medications
      and cardiomegaly. The prevalenceof intradialytic hypotension was 38.78%,
      hypertension 16.33% individuallyand both taking place 16.33%. Taken together, the
      prevalence of theseintradialytic events was 71.43% in our Hispanic population. A
      significant association was found between mortality and Beta blockers
      (BB)(P=0.044),Calcium channel blockers (CCB) (P=0.023), cardiomegaly
      (P=0.044),and intradialytic events (P=0.035). Odds ratio of multiple variables
      dis-closed that dependent variable death decreased in probability with the useof
      BB by an estimate of 73% and with the use of CCB by 74.8%. On the otherhand, odds
      of developing the dependent variable death increased by 74.5% if thepatients
      developed intradialytic events. Similarly, the odds of developing cardiomegaly in
      the living group increased by 70%. A logistic regression of multiplevariables
      found that the probability of developing the dependent condition ofdeath
      increases by almost 2.896 times if intradialytic events are present andthat there
      is a 58.9% inferred causality. It is concluded that intradialytic hyper-tension
      and hypotension are major risk factors for mortality in dialysis patients.The use
      of BB and CCB may be protetive to avoid the risk of mortality inthese patients.

PMID- 29193924
TI  - Isolated Rectus Femoris Muscle Tear in a Non-Athletic Patient: A Case Report.
AB  - Quadriceps muscle injuries are common in athletes and middle age patients.Strains
      and tears of the distal portion of the muscle is the most commonpresentation of
      these injuries. Isolated rectus femoris tears are rare andfew reports are
      published that evaluate outcomes in of nonsurgical treatmentof these injuries.
      This article will described an unusual case of isolated distalrectus femoris tear
      in a patient with no associated risk factors, who initiallypresented with
      extensor mechanism weakness and limping, treated conservativelywith range of
      motion therapy and strengthening.

PMID- 29193925
TI  - Klinefelter Syndrome (49, XXXXY/48, XXXY) associated with narrow angle glaucoma:A
      case report.
AB  - INTRODUCTION: Previous studies have described Klinefelter syndrome as a
      geneticdisorder characterized by at least one extra X chromosome and at least
      47chromosomes. It is the most common sex chromosome aneuploidy among men.Patients
      may present with large height, gynecomastia, low testosterone levels,infertility,
      hypogonadism and diseases usually more common in females suchas osteoporosis,
      breast cancer and auto-immune disorders. Other rare ophthalmicassociations have
      been described, such as diffuse choroidal atrophy, microphtalmia,cataracts,
      juvenile glaucoma, choroid colobomas and goniodysgenesis. OBJECTIVES: To report
      on the ocular findings in a Puerto Rican patient withKlinefelter syndrome
      (XXXXY/XXXY). PATIENTS AND METHODS: A patient with Klinefelter syndrome with
      revious history of elevated intraocularpressure underwent a comprehensive ocular
      examination, Humphrey visualfields and Stratus optical coherence tomography (OCT)
      tests. Patient had inreased intraocular pressure, visual field loss and OCT
      findings compatible withglaucoma. After laser YAG laser iridotomies, high IOP
      persisted. Brimonidine0.2 % drops three times a day drops were prescribed to
      lower IOP. CONCLUSIONS: A patient with Klinefelter syndrome had poor visual
      acuity, high intraocular pressure, visual fields and OCT results, all compatible
      with angle closureglaucoma as part of the syndrome.

PMID- 29193926
TI  - Acute Shortening and re-lengthening in the management of open tibia fractures
      with severe boneof 14 CMS or more and extensive soft tissue loss.
AB  - INTRODUCTION: A traumatic event to the tibia with more than 14 cm of bone andsoft
      tissue loss represents a challenge to most orthopedic surgeons and is considered
      a limb-threatening condition. Few solutions are available in such clinical
      situations and among them is the acute shortening and re-lengthening ofbone and
      soft tissue. MATERIALS AND METHODS: Our study presents the management of 7
      patientswith grade III B open fractures (according to the Gustillo
      Andersonclassification) of the tibia who underwent resectionof all the
      devitalized tissues, acute limb shortening to close the defect,application of an
      external fixator, and metaphyseal osteotomy for re-lengthening. The patient
      outcomes were basedon different parameters using the evaluation system
      established by Paley et al. RESULTS: Results acquired during the study show an
      average bone loss of 19cm(with a minimum of 14 cm and a maximum of 31.50cm). The
      average timeto full recovery of all patients was 19 months with a minimum of 14
      monthsand a max of 34 months. Patient presented with excellent bony union andnone
      existent or small refractory leg length discrepancy and did not requirebone
      grafts or free flaps. Complications that the patients had were contractures,which
      required secondary procedures such as Achilles tendon re-lengtheningand recurrent
      infections. DISCUSSION: Overall patients had excellent bone union and were able
      to perform activities of their daily living. The Ilizarov technique of
      compression-dis-traction osteogenesis is an elegant treatment option that should
      be consideredin patients suffering such traumatic events providing excellent bony
      unionand good functional outcomes for the patient.

PMID- 29193927
TI  - Pheochromocytoma in pregnancy: A case Report.
AB  - This is the case of a 38 year-old female patient with an intrauterine
      pregnancy,in which a previous incidentally identified adrenal mass proved to be
      apheochromocytoma during the antenatal period. The patient was started onalpha
      and beta-adrenergic blockade to maintain hemodynamic stability, and
      surgicalremoval of the lesion was performed during the second trimester without
      majorcomplications. In view of the rarity of this disorder in pregnancy, it is
      imperativeto have a high index of suspicion for a prompt and dedicated
      management,since this tumor, if unrecognized, is associated with high fetal and
      maternalmortality.

PMID- 29193928
TI  - Secondary Resistance to dopamine agonist after thirteen months of successful
      treatment in a 42 years old man.
AB  - Prolactinomas are the most common hormone-secreting pituitary tumorsand
      represents approximately 40% of all pituitary adenomas. Pharmacologytherapy with
      dopamine agonists is the mainstay treatment for prolactinomas.Usually, patients
      respond to these drugs with decreased level of the serumprolactin and with time,
      by tumor shrinkage. Less than 10% of patientswith prolactinomas exhibit
      resistance to the action of dopamine agonists, asdefined by the lack of
      normalization of the serum prolactin levels despite long-term treatment at high
      doses of these drugs. However secondary resistanceto dopamine agonists therapy
      has also been described in patients who wereinitially responsive to treatment,
      either with Cabergoline or Bromocriptinebut later develop dopamine agonist
      resistance, with elevated prolactin levelsand sometimes an enlarging tumor volume
      several years afterwards. Wereport a case of a male patient with prolactinoma who
      developed drug resistance13 months after initial dopamine agonist therapy.

PMID- 29193929
TI  - [The evaluation of science].
AB  - The evaluation and quantification of scientific activity is an extremely complex
      task. Evaluation of research results is often difficult, and different indicators
      for the quantification and evaluation of scientific publications have been
      identified, as well as the development and success of the training programs of
      researchers.

PMID- 29193930
TI  - [Comment on article "Severe scorpionism causing acute flaccid paralysis. Case
      report"].
AB  - No Abstract.

PMID- 29193931
TI  - [Answer to comment on article "Severe scorpionism causing  acute flaccid
      paralysis. Case report"].
AB  - No abstract.

PMID- 29193932
TI  - [Comment on article "Acute appendicitis. Surgical and non surgical treatment"].
AB  - No abstract.

PMID- 29193933
TI  - [Answer to comment on article "Acute appendicitis. Surgical and non surgical
      treatment"].
AB  - No abstract.

PMID- 29193934
TI  - [About the thesis of specialization in Medicine].
AB  - No Abstract.

PMID- 29193935
TI  - [Academic communication and honesty].
AB  - No abstract.

PMID- 29193936
TI  - [Evaluation of cardiovascular risk factors in obesity before and after bariatric
      surgery].
AB  - BACKGROUND: Mexico has one of the highest prevalences of severe obesity
      worldwide. Mortality in those patients may be as high as 90% mainly due to
      cardiovascular disease. Despite Framingham score has been validated in the
      Mexican population, it only predicts cardiovascular risk at 10 years. Meanwhile
      ASCVD10 score could evaluate risk at 10 years and through lifetime. None of these
      scores have been used for cardiovascular risk assessment in Mexican patients with
      severe obesity. METHODS: We conducted a quasi-experimental (before/ after) study
      with 109 patients with severe obesity, assessed prevalence of comorbidities,
      performed anthropometric and biochemical evaluations before and a year after
      bariatric surgery. With these results we calculated Framingham and ASCVD10 scores
      and compared them. RESULTS: Patients had a mean age of 45.3 +/- 10.1 years, 70%
      female, 79% underwent laparoscopic Roux-en-Y gastric bypass. We observed weight
      decrease at each evaluation point after surgery, independently of the surgical
      procedure. All biochemical parameters improved. Framingham score decreased from
      9.4% to 5.9%, frequency of patients classified as high-risk decreased from 25% to
      11%. ASCVD10 score decreased from 4.1% to 2.5%, patients classified as high-risk
      decreased from 28% to 16%. Tobacco use was the most important factor involved in
      cardiovascular risk. CONCLUSIONS: Cardiovascular risk at 10-years and lifetime
      decreased as soon as one year after surgery as assessed through Framingham and
      ASCVD scores.

PMID- 29193937
TI  - [Tamsulosin, oxybutynin or their combination in the treatment of ureteral stent
      related symptoms].
AB  - BACKGROUND: The aim of this paper is to compare the efficacy of tamsulosin,
      oxybutynin or their combination for the treatment of symptoms related to double J
      stent (DJS). METHODS: Randomized clinical non-blinded trial with three arms
      (tamsulosin, oxybutynin or combination) to assess the improvement of ureteral
      related symptoms with DJS with the questionnaire of Ureteral Stent Symptom
      Questionnaire (USSQ) and the adverse effects of treatment. Evaluations were made
      at 7 and 21 days after the placement of DJS. The maneuvers were compared using
      Chi squared test, Kruskall-Wallis, ANOVA and Wilcoxon considering a statistically
      significant p <= 0.05. RESULTS: 170 patients with CJJ were evaluated. A
      perprotocol analysis was performed in 142 patients, 53 received tamsulosin
      (37.4%), 42 oxybutynin (29.6%) and 47 the combination of both (33%). At 7 and 21
      days the improvement was similar in all three arms. Men with tamsulosin and women
      with oxybutynin had less general symptoms. CONCLUSIONS: Tamsulosin, oxybutynin or
      its combination similarly improve ureteral stent related symptoms and this
      improvement becomes more noticeable over time. Men are less symptomatic with
      tamsulosin and women with oxybutynin.

PMID- 29193938
TI  - [Knowledge, behavior and perception of oral health in patients with type 2
      diabetes].
AB  - BACKGROUND: Periodontal disease occurs severely in patients with diabetes, also
      causes high blood glucose. The objective of this article was to determine
      knowledge, behavior and perception of oral health in patients with type 2
      diabetes. METHODS: Cross-sectional study performed at the Unidad de Medicina
      Familiar No. 26 in Acapulco, Guerrero, Mexico; 376 patients with type 2 diabetes
      were included. Sociodemographic questionnaire, knowledge, behavior and perception
      of oral health was applied. RESULTS: 21% was sent to the dental service by the
      family doctor. 86% of the patients performed dental brushing 2-3 times a day; 57%
      perceived the relationship diabetes and oral health. In signs of oral disease
      they predominated with 34% gingival bleeding and inflammation with 30%. Main
      reason was for emergency dental surgery. CONCLUSIONS: The patient suffering from
      diabetes does not recognize the dentist as the main character in the
      comprehensive healthcare; on the other hand, the family doctor does not send a
      prevention stomatology. It is necessary to develop educational strategies focused
      on the family doctor and patient in terms of importance of oral health.

PMID- 29193939
TI  - [Prevalence of subclinical hypothyroidism in pediatric patients with drug
      resistant epilepsy].
AB  - BACKGROUND: In several studies it has been reported a high prevalence of
      subclinical hypothyroidism in children with epilepsy secondary to the use of
      monotherapy with valproic acid, carbamazepine and phenytoin. The aim of this
      article is to determine the prevalence of subclinical hypothyroidism in children
      with drug-resistant epilepsy treated at the Pediatric Neurology Service of the
      Hospital de Pediatria, Centro Medico Nacional Siglo XXI in Mexico City. METHODS:
      We conducted a descriptive cross-sectional study. All pediatric patients with
      drug-resistant epilepsy and without structural alteration seen at the pediatric
      neurology service of our hospital between January 1 and June 1 2015 were
      included. Results: Prevalence of subclinical hypothyroidism in our sample was of
      25%, with most patients receiving polytherapy with valproic acid. CONCLUSIONS:
      The intentional searching for subclinical hypothyroidism in pediatric patients
      with drug-resistant epilepsy without structural alteration might be considered as
      part of routine medical care and patients receiving combination therapy with
      valproic acid they should be considered as a subgroup with an increased risk of
      developing such comorbidity.

PMID- 29193940
TI  - [Matricaria chamomilla (aqueous extract) improves atopic dermatitis-like lesions
      in a murine model].
AB  - BACKGROUND: Matricaria Chamomilla L. (Mch), popularly known as chamomile, has
      been used for centuries as an herbolary remedy due to its broad clinical
      spectrum. The aim of this study was to evaluate the effect of Mch associated to a
      vehicle with emollient function in induced atopic dermatitis (AD)-like lesions in
      a murine model. METHODS: AD was induced with dinitrochlorobenzene on 12 male
      seven-week old BALB/c mice. Animals were divided in three groups (control, GC;
      control negative, GCN; and experimental, GE). Liquid petrolatum was applied to
      the GCN and liquid petrolatum with aqueous extract of Mch at 7% to the GE.
      Induction and evolution of the lesions were verified by biopsy at 2nd and 6th
      week. Evaluation of peripheral blood cells to correlate inflammatory cells was
      made as well at the same weeks. Lesions were clinically evaluated at 2nd, 4th and
      6th week. Scratching was monitored according to the observation methodology of
      Kobayashi et al. RESULTS: Mch aqueous extract associated to a vehicle with
      emollient function improves atopic dermatitis-like lesions after two weeks.

PMID- 29193941
TI  - [Findings of thyroid nodules in autopsies in Western Mexico].
AB  - BACKGROUND: International literature reports a prevalence of 50% of thyroid
      nodules detected during autopsies of subjects without known thyroid disease.
      Currently there are no studies of this type in Mexico. The aim was to identify
      the prevalence of thyroid nodules in autopsied bodies without known thyroid
      pathology. METHODS: A series of cases of 300 cadavers without known thyroid
      pathology, from which we obtained their thyroid glands. It was analyzed the
      presence of thyroid nodules as well as their macroscopic and microscopic
      characteristics. RESULTS: 300 autopsies were included. 123 cadavers (41%)
      presented thyroid nodules; 69 were men (56%) and 54, women (44%). The mean age
      was 37 +/- 14 years. A total of 149 nodules were found, out of which 94 were
      solid nodules (63%), and 55 were cystic (37%). Histopathological diagnosis of
      malignancy was found in 12 of the analyzed thyroid glands (4%). CONCLUSIONS:
      There was a greater prevalence of thyroid nodules in men and in subjects whose
      age at the time of dying was 45 years or less, unlike what is found in the
      international literature. We consider necessary to create screening programs for
      early diagnosis of thyroid nodules.

PMID- 29193942
TI  - [Perioperative management protocol of patients undergoing microsurgical flaps in
      main healthcare centers].
AB  - Microsurgery is one of the most fertile and innovative area in reconstructive
      surgery. Today it is considered an indispensable technique in plastic surgery
      with flaps survival rates over 95% in main healthcare centers. The factors
      involved in achieving these results are: the improvement of the surgical
      technique, adequate patient selection and careful perioperative care.
      Perioperative care starts at the initial assessment of the patient where it's
      very important to consider the indications and contraindications of these
      procedures. We use this type of reconstruction when we face complex and extensive
      defects, they are mostly of the times, difficult or impossible to reconstruct
      with other techniques. Antibiotic prophylaxis should begin an hour before initial
      incision. Free flap procedures are classified as maximum risk for venous
      thromboembolism so it's essential to indicate an appropriate prophylaxis.
      Normothermia, proper fluid management and judicious use of transfusions and
      vasopressor are a fundamental part of intraoperative care. Postoperative
      monitoring of these flaps is essential for early detection of vascular thrombosis
      in order to save the transferred tissue.

PMID- 29193943
TI  - [Cost-effectiveness of local steroid combined with therapeutic exercise in
      subacromial impingement syndrome].
AB  - BACKGROUND: The most common cause of injury is shoulder impingement syndrome.
      Management includes physical therapy, analgesics, steroids and surgery. The aim
      of the study was to determine the cost-effectiveness of using steroids combined
      with therapeutic exercise at home in the chronic impingement syndrome. METHODS:
      Clinical trial randomized in 30 people with subacromial impingement syndrome
      underwent two treatments: steroid and at home rehabilitation booklet evaluated at
      the first and fourth week through UCLA Shoulder rating scale. RESULTS: We studied
      17 men (56.7 %) and 13 women (43.3 %), mean age was 42.87 years. Group 2 earned
      greater improvement in UCLA Shoulder rating scale 18.87 at baseline and 27.60 at
      the end. With 30.27 accumulated disability days for group 1, and 14.80 for group
      2. CONCLUSIONS: The combination of local steroids with therapeutic exercise is
      more effective clinically and declining disability compared to conventional
      physical therapy.

PMID- 29193944
TI  - [Atypical deletions in Williams-Beuren syndrome].
AB  - The Williams-Beuren (SWB; OMIM 194050) syndrome is an autosomal dominant
      multisystem disorder that occurs in ~ 1 in 20,000 live births and results from a
      7q11.23 deletion spanning ~ 28 genes. This deletion is caused by a nonallelic
      homologous recombination (NAHR) between low copy repeats present therein. The SWB
      phenotype is characterized by neonatal hypercalcemia, mental disability,
      distinctive personality and cognitive profile, short stature, dysmorphic facies,
      connective tissue disorders and supravalvular aortic stenosis. Ninety percent of
      the deletions are of 1.5 Mb, 8% of 1.84Mb, and only 2% are atypical. Although
      only ~ 40 atypical deletions have been described, they have contributed to
      clarify the genotype-phenotype correlation and allowed for a more integrative
      management. In this review we highlight the importance of detecting atypical
      deletions in patients with SWB.

PMID- 29193945
TI  - [The pulmonary hypertension of the chronic kidney disease].
AB  - Pulmonary hypertension in chronic kidney disease is included in the group 5 of
      the pulmonary hypertension classification of the World Health Organization. Its
      mechanism is multifactorial and little known. Its importance has increased due to
      its impact on survival according to whether they received a kidney transplant,
      the greater risk of early renal graft loss and major hospital stays. In this
      review, we analyze the panorama of chronic renal disease in Mexico and Latin
      America, the epidemiology, pathophysiological mechanisms, the diagnostic process
      and the treatment of pulmonary hypertension in chronic kidney disease.

PMID- 29193946
TI  - [Basic guidelines of the Instituto Mexicano del Seguro Social scientific research
      networks].
AB  - Scientific Research Networks of the Instituto Mexicano del Seguro Social were
      proposed as a strategy to promote collaboration between health personnel,
      following basic guidelines to include the priority health problems of the
      Institute, the multidisciplinary, interdisciplinary and multicentric cooperation
      between researchers and health care personnel leaders in each field and
      discipline of knowledge, as well as the generation of confidence among the group
      of participants through the signing of confidentiality agreements, and avoiding
      the predominance of leadership. To achieve this, the Coordination of Health
      Research accompanies the personnel in the conduction of logistic and
      administrative aspects.

PMID- 29193947
TI  - [Tuberculosis caused by Mycobacterium bovis, a re-emerging infection?]
AB  - Currently, tuberculosis (TB) is a public health problem, is present in all
      regions of the world and remains one of the most deadly communicable diseases,
      particularly associated with infection by the human immunodeficiency virus (HIV).
      Cases of TB Mycobacterium bovis more and more frequent, especially in vulnerable
      populations. TB caused by M. bovis clinical, radiological and histologically
      indistinguishable from tuberculosis caused by M. tuberculosis; however, there are
      some differences that make M. tuberculosis particular. The direct correlation
      between infection with M. bovis in cattle and human disease has been well
      documented, but the true prevalence is underestimated. Overall, the proportion of
      cases of human TB caused by M. bovis is low compared with M. tuberculosis, but
      its potential in the groups most at risk impact should not be underestimated by
      the impact on morbidity and mortality.

PMID- 29193948
TI  - [Bayesian tragedy, from clinical iatrogenesis to biotechnology].
AB  - Diagnostic algorithms, as well as the biotechnological design, require the
      calculation of conditional probability, given the presence of certain positive
      data, in the context of prevalence, sensitivity and specificity; It is necessary
      to estimate the probability that the patient has a certain disease. Sometimes,
      with a test of scrutiny, it goes from a probability of 1/1000 to 1/20,
      constituting a great diagnostic advance, reducing the uncertainty spectacularly;
      However, the tragedy is that most doctors believe that the probability changed
      from 0.1% (1/1000) to more than 90%, which is outrageously wrong. Iatrogeny
      arises from the error in answering the question: "given that the test is
      positive, what is the probability that the patient has the disease?" In other
      cases, tragedy is to apply a test to an individual belonging to a subpopulation
      for which it was not designed. In addition, it is evident that the fascination
      for the sensitivity avoids the application of less sensitive methods in
      populations that are abandoned; It is not a matter of making better tests than
      those that the State does to the patients it attends, but of making less accurate
      tests for the patients that the State does not attend.

PMID- 29193949
TI  - [Case series of Clostridium difficile NAP1/027/BI with novels treatments].
AB  - BACKGROUND: Clostridium difficile is a spore-forming bacterium, producing
      exotoxins, causing potentially fatal nosocomial diarrhea. They have recently
      reported outbreaks of C. difficile ribotype 027, which is characterized by a
      hypervirulent strain and high resistance to standard therapy. CLINICAL CASE: We
      present three cases of Clostridium difficile NAP1/027/BI associated infection,
      they were presented with different clinical manifestations. Two of the patients
      were successfully treated with the combination of vancomycin plus tigecycline.
      The other case was treated with fecal microbiota transplant, with resolution of
      the disease. CONCLUSION: in patients with Clostridium difficile NAP1/027/BI
      associated infection is a good therapeutic option to consider the use of
      tigecycline in conjunction with vancomycin, as well as fecal microbiota
      transplantation.

PMID- 29193950
TI  - [Unicentric Castleman's disease in cervical back space neck].
AB  - BACKGROUND: Castleman's disease is a rare, benign condition of lymphoid tissue.
      There are two clinical types: unicentric and multicentric with three histological
      variants, hyaline-vascular, plasma celular and mixed. The most common sites of
      this are mediastinum, adbomen and neck. Magnetic resonance imaging is well suited
      to depict the characteristics of the masses and their relationship to adjacent
      structures. The knowledge of this disease and its inclusion in the differential
      diagnosis from other neck masses will contribute to the therapeutic approach.
      CLINICAL CASE: A 21 years old female patient with a left neck mass characterized
      by magnetic resonance as solid, heterogeneous, vascularized lesion, pre
      dominantly isointensa on T1-weighted images an high signal on T2-weighted images
      and fat sat that demonstrate moderate enhancement after contraste material
      administration located in posterior space of the neck with extension at thoracic
      outlet displacing structures of carotid, anterior cervical and viceral spaces.
      She underwent complete surgical resection of the mass with histopathological
      diagnosis of hyaline-vascular type of Castleman's disease. CONCLUSION: Magnetic
      resonance is well suited to depict characteristic and the extent of mass in the
      neck contributing to narrow the differential diagnosis. Imaging findings,
      especially of magnetic resonance are very important to choose the treatment of
      Castleman's disease.

PMID- 29193951
TI  - [Disseminated tuberculosis in a patient with overlap syndrome, challenges in
      preventing].
AB  - Patients with autoimmune rheumatic diseases are at increased risk for developing
      infections and these are associated with increased morbidity and mortality from
      these diseases, especially in patients with systemic lupus erythematosus,
      rheumatoid arthritis, systemic sclerosis and autoimmune inflammatory myopathies.
      The objective of this paper is to address the challenges in detecting latent
      tuberculosis in immunosuppressed patients and the initiation of prophylactic
      treatment because currently there are no well-defined guidelines indicating what
      action to take for detection and treatment; so far the available scientific
      evidence is scarce and some methodological shortcomings.

PMID- 29193952
TI  - [Transient central diabetes insipidus associated with pregnancy. Case report and
      bibliography review].
AB  - The case of a patient affected by transient diabetes insipidus associated with
      pregnancy, in the context of eclampsia, which was presented during seizures and
      identified by polyuria important, as well as changes in the urinary density
      occurs, and improving after nasal administration of desmopressin, which confirmed
      the diagnosis and treatment served completely by sending the picture without any
      sequel.

PMID- 29193953
TI  - Clinical profile, bacterial isolates, and antibiotic resistance of corneal ulcers
      in Puerto Rico.

PMID- 29193954
TI  - Improvement of Transparent Conducting Performance on Oxygen-Activated Fluorine
      Doped Tin Oxide Electrodes Formed by Horizontal Ultrasonic Spray Pyrolysis
      Deposition.
AB  - In this study, highly transparent conducting fluorine-doped tin oxide (FTO)
      electrodes were fabricated using the horizontal ultrasonic spray pyrolysis
      deposition. In order to improve their transparent conducting performances, we
      carried out oxygen activation by adjusting the ratio of O2/(O2+N2) in the carrier
      gas (0%, 20%, and 50%) used during the deposition process. The oxygen activation
      on the FTO electrodes accelerated the substitution concentration of F (FO*) into
      the oxygen sites in the FTO electrode while the oxygen vacancy (VO**)
      concentration was reduced. In addition, due to growth of pyramid-shaped
      crystallites with (200) preferred orientations, this oxygen activation caused the
      formation of a uniform surface structure. As a result, compared to others, the
      FTO electrode prepared at 50% O2 showed excellent electrical and optical
      properties (sheet resistance of ~4.0 +/- 0.14 Omega/?, optical transmittance of
      ~85.3%, and figure of merit of ~5.09 +/- 0.19 * 10-2 Omega-1). This led to a
      superb photoconversion efficiency (~7.03 +/- 0.20%) as a result of the improved
      short-circuit current density. The photovoltaic performance improvement can be
      defined by the decreased sheet resistance of FTO used as a transparent conducting
      electrode in dye-sensitized solar cells (DSSCs), which is due to the combined
      effect of the high carrier concentration by the improved FO* concentration on the
      FTO electrodes and the fasted Hall mobility by the formation of a uniform FTO
      surface structure and distortion relaxation on the FTO lattices resulting from
      the reduced VO*** concentration.

PMID- 29193955
TI  - Polymeric Nanoparticle-Coated Pickering Emulsion-Synthesized Conducting
      Polyaniline Hybrid Particles and Their Electrorheological Study.
AB  - To produce an electric stimuli-responsive electrorheological (ER) material,
      semiconducting core/shell-type polyaniline (PANI) hybrid particles were
      fabricated through Pickering emulsion-type polymerization, using
      poly(divinylbenzene-alt-maleic anhydride) (PDVMA) particles as a solid
      surfactant. The PDVMA nanoparticles were initially polymerized using a self
      stable precipitation method. The fabricated PANI/PDVMA composite particles were
      subjected to various chemical characterizations; further, they were suspended in
      silicone oil at 10 vol % to prepare an ER fluid, and their viscoelastic behaviors
      were scrutinized using a rheometer under various input electric fields. We also
      adopted an LCR meter to evaluate its dielectric characteristics. Our results
      showed that the PANI/PDVMA composite particles display typical ER performance,
      such that both dynamic and elastic yield stresses follow a polarization mechanism
      with a slope of 2.0.

PMID- 29193956
TI  - Native-MS Analysis of Monoclonal Antibody Conjugates by Fourier Transform Ion
      Cyclotron Resonance Mass Spectrometry.
AB  - Antibody-drug conjugates (ADCs) are an important class of therapeutic molecule
      currently being used to treat HER2-positive metastatic breast cancer, relapsed or
      refractory Hodgkin lymphoma, systemic anaplastic large cell lymphoma, relapsed or
      refractory B-cell precursor acute lymphoblastic leukemia, and acute myeloid
      leukemia. An ADC typically consists of a small molecule or peptide-based
      cytotoxic moiety covalently linked, via lysine or cysteine residues, to a
      monoclonal antibody (mAb) scaffold. Mass spectrometric (MS) characterization of
      these molecules affords highly accurate molecular weight (MW) and drug-to
      antibody ratio (DAR) determination and is typically performed using orthogonal
      acceleration time-of-flight (oa-ToF) analyzers and more recently, Orbitrap
      instruments. Herein we describe for the first time the use of a 15 T solariX
      Fourier transform ion cyclotron mass spectrometer to characterize an IgG1 mAb
      molecule conjugated with biotin via native lysine and cysteine residues, under
      native-MS and solution conditions. The cysteine-biotin conjugates remained fully
      intact, demonstrating the ability of the FT-ICR to maintain the noncovalent
      interactions and efficiently transmit labile protein complexes. Native-MS was
      acquired and is displayed in magnitude mode using a symmetric Hann apodization
      function. Baseline separation is achieved on all covalent biotin additions, for
      each charge state, for both the lysine- and cysteine-biotin conjugates. Average
      DAR values obtained by native-MS for the lysine conjugate are compared to those
      derived by denaturing reversed phase liquid chromatography using an oa-ToF MS
      system (1.56 +/- 0.02 versus 2.24 +/- 0.02 for the 5 equivalent and 3.99 +/- 0.09
      versus 4.43 +/- 0.01 for the 10 equivalent, respectively). Increased DAR value
      accuracy can be obtained for the higher biotin-load when using standard ESI
      conditions as opposed to nanoESI native-MS conditions.

PMID- 29193957
TI  - Functional Characterization of Insulation Effect for Synthetic Gene Circuits in
      Mammalian Cells.
AB  - Insulators are noncoding gene regulatory elements in eukaryotic genome, which
      function as chromatin partitioning boundaries, and block interference across
      different chromatin domains. To facilitate modular construction of synthetic gene
      circuit that is usually composed of multiple transcription cassettes, unwanted
      cross-regulations between different cassettes should be avoided. Here, we
      developed a quantitative method to characterize the functional effect of three
      insulators on the cross-regulations of six promoters in mammalian cells. We
      showed that the unwanted cross-regulations displayed a threshold-like effect, and
      the threshold position varied along with the context of promoters and insulators.
      We tested the function of insulators in both cascade and sensory switch circuits
      assembled in episomal plasmid vectors, and showed that the insulation effect was
      mainly revealed on the first regulatory layer of the cascade circuit. A deviation
      on the response curve of the sensory switch circuit with or without insulators
      was observed, but response intensity of some sensory switch circuits were not
      affected. Therefore, our results provided a general guide on the selection of
      insulators with varying promoters in episomal synthetic gene circuits in
      mammalian cells, which may be useful to reduce the effect of the unwanted cross
      regulations.

PMID- 29193958
TI  - Crosstalk between Diverse Synthetic Protein Degradation Tags in Escherichia coli.
AB  - Recently, a synthetic circuit in E. coli demonstrated that two proteins
      engineered with LAA tags targeted to the native protease ClpXP are susceptible to
      crosstalk due to competition for degradation between proteins. To understand
      proteolytic crosstalk beyond the single protease regime, we investigated in E.
      coli a set of synthetic circuits designed to probe the dynamics of existing and
      novel degradation tags fused to fluorescent proteins. These circuits were tested
      using both microplate reader and single-cell assays. We first quantified the
      degradation rates of each tag in isolation. We then tested if there was crosstalk
      between two distinguishable fluorescent proteins engineered with identical or
      different degradation tags. We demonstrated that proteolytic crosstalk was indeed
      not limited to the LAA degradation tag, but was also apparent between other
      diverse tags, supporting the complexity of the E. coli protein degradation
      system.

PMID- 29193959
TI  - Sacrificial Interlayer for Promoting Charge Transport in Hematite Photoanode.
AB  - The semiconductor/electrolyte interface plays a crucial role in
      photoelectrochemical (PEC) water-splitting devices as it determines both
      thermodynamic and kinetic properties of the photoelectrode. Interfacial
      engineering is central for the device performance improvement. Taking the cheap
      and stable hematite (alpha-Fe2O3) wormlike nanostructure photoanode as a model
      system, we design a facile sacrificial interlayer approach to suppress the
      crystal overgrowth and realize Ti doping into the crystal lattice of alpha-Fe2O3
      in one annealing step as well as to avoid the consequent anodic shift of the
      photocurrent onset potential, ultimately achieving five times increase in its
      water oxidation photocurrent compared to the bare hematite by promoting the
      transport of charge carriers, including both separation of photogenerated charge
      carriers within the bulk semiconductor and transfer of holes across the
      semiconductor-electrolyte interface. Our research indicates that understanding
      the semiconductor/electrolyte interfacial engineering mechanism is pivotal for
      reconciling various strategies in a beneficial way, and this simple and cost
      effective method can be generalized into other systems aiming for efficient and
      scalable solar energy conversion.

PMID- 29193960
TI  - Continuous and High-Throughput Electromechanical Lysis of Bacterial Pathogens
      Using Ion Concentration Polarization.
AB  - Electrical lysis of mammalian cells has been a preferred method in microfluidic
      platforms because of its simple implementation and rapid recovery of lysates
      without additional reagents. However, bacterial lysis typically requires at least
      a 10-fold higher electric field (~10 kV/cm), resulting in various technical
      difficulties. Here, we present a novel, low-field-enabled electromechanical lysis
      mechanism of bacterial cells using electroconvective vortices near ion selective
      materials. The vortex-assisted lysis only requires a field strength of ~100 V/cm,
      yet it efficiently recovers proteins and nucleic acids from a variety of
      pathogenic bacteria and operates in a continuous and ultrahigh-throughput (>1
      mL/min) manner. Therefore, we believe that the electromechanical lysis will not
      only facilitate microfluidic bacterial sensing and analysis but also various high
      volume applications such as the energy-efficient recovery of valuable metabolites
      in biorefinery pharmaceutical industries and the disinfection of large-volume
      fluid for the water and food industries.

PMID- 29193961
TI  - Chemical Proteomics Reveals Soluble Epoxide Hydrolase as a Therapeutic Target for
      Ocular Neovascularization.
AB  - The standard-of-care therapeutics for the treatment of ocular neovascular
      diseases like wet age-related macular degeneration (AMD) are biologics targeting
      vascular endothelial growth factor signaling. There are currently no FDA approved
      small molecules for treating these blinding eye diseases. Therefore, therapeutic
      agents with novel mechanisms are critical to complement or combine with existing
      approaches. Here, we identified soluble epoxide hydrolase (sEH), a key enzyme for
      epoxy fatty acid metabolism, as a target of an antiangiogenic homoisoflavonoid,
      SH-11037. SH-11037 inhibits sEH in vitro and in vivo and docks to the substrate
      binding cleft in the sEH hydrolase domain. sEH levels and activity are up
      regulated in the eyes of a choroidal neovascularization (CNV) mouse model. sEH is
      overexpressed in human wet AMD eyes, suggesting that sEH is relevant to
      neovascularization. Known sEH inhibitors delivered intraocularly suppressed CNV.
      Thus, by dissecting a bioactive compound's mechanism, we identified a new
      chemotype for sEH inhibition and characterized sEH as a target for blocking the
      CNV that underlies wet AMD.

PMID- 29193962
TI  - Cell Penetrating Polymers Containing Guanidinium Trigger Apoptosis in Human
      Hepatocellular Carcinoma Cells unless Conjugated to a Targeting N-Acetyl
      Galactosamine Block.
AB  - A series of 3-guanidinopropyl methacrylamide (GPMA)-based polymeric gene delivery
      vehicles were developed via aqueous reversible addition-fragmentation chain
      transfer (RAFT) polymerization. The polymers have been evaluated for their
      cellular internalization ability, transfection efficiency, and cytotoxicity. Two
      homopolymers: P(GPMA20), P(GPMA34), were synthesized to study the effect of
      guanidium polymer length on delivery efficiency and toxicity. In addition, an N
      acetyl-d-galactosamine (GalNAc)-based hydrophilic block was incorporated to
      produce diblock polymers, which provides a neutral hydrophilic block that
      sterically protects plasmid-polymer complexes (polyplexes) from colloidal
      aggregation and aids polyplex targeting to hepatocytes via binding to
      asialoglycoprotein receptors (ASGPRs). Polyplexes formed with P(GPMAx) (x = 20,
      34) homopolymers were shown to be internalized via both energy-dependent and
      independent pathways, whereas polyplexes formed with block polymers were
      internalized through endocytosis. Notably, P(GPMAx) polyplexes enter cells very
      efficiently but are also very toxic to human hepatocellular carcinoma (HepG2)
      cells and triggered cell apoptosis. In comparison, the presence of a carbohydrate
      block in the polymer structures reduced the cytotoxicity of the polyplex
      formulations and increased gene delivery efficiency with HepG2 cells.
      Transfection efficiency and toxicity studies were also carried out with HEK 293T
      (human embryonic kidney) cells for comparison. Results showed that polyplexes
      formed with the P(GPMAx) homopolymers exhibit much higher transfection efficiency
      and lower toxicity with HEK 293T cells. The presence of the carbohydrate block
      did not further increase transfection efficiency in comparison to the
      homopolymers with HEK 293T cells, likely due to the lack of ASGPRs on the HEK
      293T cell line. This study revealed that although guanidinium-based polymers have
      high membrane permeability, their application as plasmid delivery vehicles may be
      limited by their high cytotoxicity to certain cell types. Thus, the use of cell
      penetrating structures in polyplex formulations should be used with caution and
      carefully tailored toward individual cell/tissue types.

PMID- 29193963
TI  - Aza Diels-Alder Reactions of Nitriles, N,N-Dimethylhydrazones, and Oximino
      Ethers. Application in Formal [2 + 2 + 2] Cycloadditions for the Synthesis of
      Pyridines.
AB  - Metal-free, formal [2 + 2 + 2] cycloaddition strategies for the synthesis of
      polycyclic pyridine derivatives are described. The overall transformation
      proceeds via a two-stage pericyclic cascade mechanism. In the first step, an
      intramolecular propargylic ene reaction generates a vinylallene that is
      necessarily locked in the s-cis conformation. This vinylallene exhibits
      exceptional reactivity as a Diels-Alder reaction partner and engages in [4 + 2]
      cycloadditions with normally unreactive azadienophiles including unactivated
      cyano groups and heterosubstituted imine derivatives such as dimethylhydrazones
      and oximino ethers. Few examples of oximino ether Diels-Alder reactions have been
      reported previously, and normal electron-demand [4 + 2] cycloadditions of
      unactivated dialkylhydrazones are unprecedented. Overall, this metal-free formal
      [2 + 2 + 2] cycloaddition provides access to polycyclic pyridine derivatives and
      complements transition-metal-catalyzed [2 + 2 + 2] strategies.

PMID- 29193964
TI  - Out-of-Equilibrium Aggregates and Coatings during Seeded Growth of Metallic
      Nanoparticles.
AB  - Although dissipative self-assembly is ubiquitous in nature, where it gives rise
      to structures and functions critical to life, examples of artificial systems
      featuring this mode of self-assembly are rare. Here, we identify the presence of
      ephemeral assemblies during seeded growth of gold nanoparticles. In this process,
      hydrazine reduces Au(III) ions, which attach to the existing nanoparticles
      "seeds". The attachment is accompanied by a local increase in the concentration
      of a surfactant, which therefore forms a bilayer on nanoparticle surfaces,
      inducing their assembly. The resulting aggregates gradually disassemble as the
      surfactant concentration throughout the solution equilibrates. The lifetimes of
      the out-of-equilibrium aggregates depend on and can be controlled by the size of
      the constituent nanoparticles. We demonstrate the utility of our out-of
      equilibrium aggregates to form transient reflective coatings on polar surfaces.

PMID- 29193966
TI  - A Photochemical Route to 3- and 4-Hydroxy Derivatives of 2-Aminocyclobutane-1
      carboxylic Acid with an all-cis Geometry.
AB  - Short gram-scale syntheses of both enantiomers of 2-amino-3-hydroxycyclobutane-1
      carboxylic acid and of 2-amino-4-hydroxycyclobutanecarboxylic acid with an all
      cis geometry are described. The sequences feature highly endo-selective [2 + 2]
      photocycloaddition reactions followed by fully regioselective ring
      opening/Hofmann rearrangement/nitrogen protection, in a consecutive or one-pot
      protocol, followed by efficient resolution using a chiral oxazolidinone.

PMID- 29193965
TI  - Stability and Water Accessibility of the Trimeric Membrane Anchors of the HIV-1
      Envelope Spikes.
AB  - HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral
      entry. Recent studies showed that its transmembrane domain (TMD) forms a trimer
      in lipid bilayer whose structure has several peculiar features that remain
      difficult to explain. One is the presence of an arginine R696 in the middle of
      the TM helix. Additionally, the N- and C-terminal halves of the TM helix form
      trimeric cores of opposite nature (hydrophobic and hydrophilic, respectively).
      Here we determined the membrane partition and solvent accessibility of the TMD in
      bicelles that mimic a lipid bilayer. Solvent paramagnetic relaxation enhancement
      analysis showed that the R696 is indeed positioned close to the center of the
      bilayer, but, surprisingly, can exchange rapidly with water as indicated by
      hydrogen-deuterium exchange measurements. The solvent accessibility of R696 is
      likely mediated by the hydrophilic core, which also showed fast water exchange.
      In contrast, the N-terminal hydrophobic core showed extremely slow solvent
      exchange, suggesting the trimer formed by this region is extraordinarily stable.
      Our data explain how R696 is accommodated in the middle of the membrane while
      reporting the overall stability of the Env TMD trimer in lipid bilayer.

PMID- 29193967
TI  - Structure-Guided Discovery of Novel, Potent, and Orally Bioavailable Inhibitors
      of Lipoprotein-Associated Phospholipase A2.
AB  - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a promising therapeutic
      target for atherosclerosis, Alzheimer's disease, and diabetic macular edema. Here
      we report the identification of novel sulfonamide scaffold Lp-PLA2 inhibitors
      derived from a relatively weak fragment. Similarity searching on this fragment
      followed by molecular docking leads to the discovery of a micromolar inhibitor
      with a 300-fold potency improvement. Subsequently, by the application of a
      structure-guided design strategy, a successful hit-to-lead optimization was
      achieved and a number of Lp-PLA2 inhibitors with single-digit nanomolar potency
      were obtained. After preliminary evaluation of the properties of drug-likeness in
      vitro and in vivo, compound 37 stands out from this congeneric series of
      inhibitors for good inhibitory activity and favorable oral bioavailability in
      male Sprague-Dawley rats, providing a quality candidate for further development.
      The present study thus clearly demonstrates the power and advantage of integrally
      employing fragment screening, crystal structures determination, virtual
      screening, and medicinal chemistry in an efficient lead discovery project,
      providing a good example for structure-based drug design.

PMID- 29193968
TI  - Structural Insight into the Photochemistry of Split Green Fluorescent Proteins: A
      Unique Role for a His-Tag.
AB  - Oligohistidine affinity tags (His-tags) are commonly fused to proteins to aid in
      their purification via metal affinity chromatography. These His-tags are
      generally assumed to have minimal impact on the properties of the fusion protein,
      as they have no propensity to form ordered elements, and are small enough not to
      significantly affect the solubility or size. Here we report structures of two
      variants of truncated green fluorescent protein (GFP), i.e., split GFP with a
      beta-strand removed, that were found to behave differently in the presence of
      light. In these structures, the N-terminal His-tag and several neighboring
      residues play a highly unusual structural and functional role in stabilizing the
      truncated GFP by substituting as a surrogate beta-strand in the groove vacated by
      the native strand. This finding provides an explanation for the seemingly very
      different peptide binding and photodissociation properties of split proteins
      involving beta-strands 10 and 11. We show that these truncated GFPs can bind
      other non-native sequences, and this promiscuity invites the possibility for
      rational design of sequences optimized for strand binding and photodissociation,
      both useful for optogenetic applications.

PMID- 29193969
TI  - Synthesis and Study at a Solid/Liquid Interface of Porphyrin Dimers Linked by
      Metal Ions.
AB  - Several porphyrin dimers linked by metal ions were prepared. One trimeric
      compound was also isolated and one porphyrin dimer linked by palladium(II) could
      be structurally characterized. In solution, the size of the new compounds was
      estimated by DOSY NMR techniques. These compounds all contained long aliphatic
      chains (O-C12H25), which were used to assemble them at a highly oriented
      pyrolytic graphite (HOPG)/liquid interface. The highly ordered arrays were
      visualized by scanning tunneling microscopy (STM).

PMID- 29193971
TI  - On-the-Fly Computation of Frontal Orbitals in Density Matrix Expansions.
AB  - We propose a method for computation of frontal (homo and lumo) orbitals in
      recursive polynomial expansion algorithms for the density matrix. Such algorithms
      give a computational cost that increases only linearly with system size for
      sufficiently sparse systems, but a drawback compared to the traditional
      diagonalization approach is that molecular orbitals are not readily available.
      Our method is based on the idea to use the polynomial of the density matrix
      expansion as an eigenvalue filter giving large separation between eigenvalues
      around homo and lumo [ Rubensson et al. J. Chem. Phys. 2008 , 128 , 176101 ].
      This filter is combined with a shift-and-square (folded spectrum) method to move
      the desired eigenvalue to the end of the spectrum. In this work we propose a
      transparent way to select recursive expansion iteration and shift for the
      eigenvector computation that results in a sharp eigenvalue filter. The filter is
      obtained as a byproduct of the density matrix expansion, and there is no
      significant additional cost associated either with its construction or with its
      application. This gives a clear-cut and efficient eigenvalue solver that can be
      used to compute homo and lumo orbitals with sufficient accuracy in a small
      fraction of the total recursive expansion time. Our algorithms make use of recent
      homo and lumo eigenvalue estimates that can be obtained at negligible cost [
      Rubensson et al. SIAM J. Sci. Comput . 2014 , 36 , B147 ]. We illustrate our
      method by performing self-consistent field calculations for large scale systems.

PMID- 29193972
TI  - Properties of Single-Walled Aluminosilicate Nanotube/Poly(vinyl alcohol) Aqueous
      Dispersions.
AB  - The properties of (synthesized) single-walled aluminosilicate nanotube (AlSiNT;
      light-scattering characterized length ~2000 +/- 230 nm and diameter ~35 +/- 4 nm)
      dispersed in an aqueous poly(vinyl alcohol) (PVA) solution (10 wt %) are
      systematically explored using a comprehensive combination of
      (polarized/depolarized) dynamic light scattering, rheological, rheo-optical, and
      scanning electron microscopy analysis schemes. The nanotube/polymer dispersions
      under investigation are promising for their fair nanotube dispersion in pristine
      aqueous media (e.g., without salt or acid addition), as well as for the optical
      transparency that greatly facilitates systematic exploration of structural
      features and dispersion state that are practically inaccessible for many of their
      (opaque) companions such as carbon nanotube dispersions. We provide the first in
      depth analysis revealing excellent dispersion state of (unmodified) AlSiNT in the
      PVA matrix, giving rise to (critical) gel-like features and substantially
      promoted elasticity that can be utilized, as a practical assessment, to produce
      uniform and defect-free electrospun nanofibers. Additionally, there is
      unambiguous evidence of nematic liquid crystal-like "wagging" (strain-invariant,
      periodic oscillation) under steady shear flow, a phenomenon previously unreported
      for nanotube composite materials. Overall, the present findings suggest that
      AlSiNT/PVA dispersions possess promising rheological, optical, and
      electrospinning properties that are highly desirable for current
      nanotechnological applications, and may serve as an ideal model system for
      establishing structure-performance relationships for like nanotube/polymer
      composite materials.

PMID- 29193970
TI  - Predicted Biological Activity of Purchasable Chemical Space.
AB  - Whereas 400 million distinct compounds are now purchasable within the span of a
      few weeks, the biological activities of most are unknown. To facilitate access to
      new chemistry for biology, we have combined the Similarity Ensemble Approach
      (SEA) with the maximum Tanimoto similarity to the nearest bioactive to predict
      activity for every commercially available molecule in ZINC. This method, which we
      label SEA+TC, outperforms both SEA and a naive-Bayesian classifier via predictive
      performance on a 5-fold cross-validation of ChEMBL's bioactivity data set
      (version 21). Using this method, predictions for over 40% of compounds (>160
      million) have either high significance (pSEA >= 40), high similarity (ECFP4MaxTc
      >= 0.4), or both, for one or more of 1382 targets well described by ligands in
      the literature. Using a further 1347 less-well-described targets, we predict
      activities for an additional 11 million compounds. To gauge whether these
      predictions are sensible, we investigate 75 predictions for 50 drugs lacking a
      binding affinity annotation in ChEMBL. The 535 million predictions for over 171
      million compounds at 2629 targets are linked to purchasing information and
      evidence to support each prediction and are freely available via
      https://zinc15.docking.org and https://files.docking.org .

PMID- 29193973
TI  - A Multicomponent Route to Functionalized Amides and Oxazolidinones.
AB  - An organobase-mediated multicomponent reaction of unactivated esters, epoxides,
      and amines is reported, furnishing functionalized amide derivatives. A wide range
      of substrates are tolerated under the reaction conditions, including chiral
      epoxides, which react with no erosion of enantiopurity. Facile modification of
      the method through replacing the ester derivative with dimethyl carbonate enables
      access to the corresponding oxazolidinone derivatives.

PMID- 29193974
TI  - Atomically Visualizing Elemental Segregation-Induced Surface Alloying and
      Restructuring.
AB  - Using in situ transmission electron microscopy that spatially and temporally
      resolves the evolution of the atomic structure in the surface and subsurface
      regions, we find that the surface segregation of Au atoms in a Cu(Au) solid
      solution results in the nucleation and growth of a (2 * 1) missing-row
      reconstructed, half-unit-cell thick L12 Cu3Au(110) surface alloy. Our in situ
      electron microscopy observations and atomistic simulations demonstrate that the
      (2 * 1) reconstruction of the Cu3Au(110) surface alloy remains as a stable
      surface structure as a result of the favored Cu-Au diatom configuration.

PMID- 29193975
TI  - Aqueous Lubrication, Structure and Rheological Properties of Whey Protein
      Microgel Particles.
AB  - Aqueous lubrication has emerged as an active research area in recent years due to
      its prevalence in nature in biotribological contacts and its enormous
      technological soft-matter applications. In this study, we designed aqueous
      dispersions of biocompatible whey-protein microgel particles (WPM) (10-80 vol %)
      cross-linked via disulfide bonding and focused on understanding their
      rheological, structural and biotribological properties (smooth
      polydimethylsiloxane (PDMS) contacts, Ra < 50 nm, ball-on-disk set up). The WPM
      particles (Dh = 380 nm) displayed shear-thinning behavior and good lubricating
      performance in the plateau boundary as well as the mixed lubrication regimes. The
      WPM particles facilitated lubrication between bare hydrophobic PDMS surfaces
      (water contact angle 108 degrees ), leading to a 10-fold reduction in boundary
      friction force with increased volume fraction (phi >= 65%), largely attributed to
      the close packing-mediated layer of particles between the asperity contacts
      acting as "true surface-separators", hydrophobic moieties of WPM binding to the
      nonpolar surfaces, and particles employing a rolling mechanism analogous to "ball
      bearings", the latter supported by negligible change in size and microstructure
      of the WPM particles after tribology. An ultralow boundary friction coefficient,
      MU <= 0.03 was achieved using WPM between O2 plasma-treated hydrophilic PDMS
      contacts coated with bovine submaxillary mucin (water contact angle 47 degrees ),
      and electron micrographs revealed that the WPM particles spread effectively as a
      layer of particles even at low phi~ 10%, forming a lubricating load-bearing film
      that prevented the two surfaces from true adhesive contact. However, above an
      optimum volume fraction, MU increased in HL+BSM surfaces due to the
      interpenetration of particles that possibly impeded effective rolling, explaining
      the slight increase in friction. These effects are reflected in the highly shear
      thinning nature of the WPM dispersions themselves plus the tendency for the
      apparent viscosity to fall as dispersions are forced to very high volume
      fractions. The present work demonstrates a novel approach for providing ultralow
      friction in soft polymeric surfaces using proteinaceous microgel particles that
      satisfy both load bearing and kinematic requirements. These findings hold great
      potential for designing biocompatible particles for aqueous lubrication in
      numerous soft matter applications.

PMID- 29193976
TI  - Time-Resolved Kinetic Chirped-Pulse Rotational Spectroscopy in a Room-Temperature
      Flow Reactor.
AB  - Chirped-pulse Fourier transform millimeter-wave spectroscopy is a potentially
      powerful tool for studying chemical reaction dynamics and kinetics. Branching
      ratios of multiple reaction products and intermediates can be measured with
      unprecedented chemical specificity; molecular isomers, conformers, and
      vibrational states have distinct rotational spectra. Here we demonstrate chirped
      pulse spectroscopy of vinyl cyanide photoproducts in a flow tube reactor at
      ambient temperature of 295 K and pressures of 1-10 MUbar. This in situ and time
      resolved experiment illustrates the utility of this novel approach to
      investigating chemical reaction dynamics and kinetics. Following 193 nm
      photodissociation of CH2CHCN, we observe rotational relaxation of energized HCN,
      HNC, and HCCCN photoproducts with 10 MUs time resolution and sample the
      vibrational population distribution of HCCCN. The experimental branching ratio
      HCN/HCCCN is compared with a model based on RRKM theory using high-level ab
      initio calculations, which were in turn validated by comparisons to Active
      Thermochemical Tables enthalpies.

PMID- 29193977
TI  - Comment on "In Vivo Drug Delivery Performance of Lipiodol-Based Emulsion or Drug
      Eluting Beads in Patients with Hepatocellular Carcinoma".

PMID- 29193978
TI  - Heterogenization of a [NiFe] Hydrogenase Mimic through Simple and Efficient
      Encapsulation into a Mesoporous MOF.
AB  - In the quest for new, efficient, and noble-metal-free H2-evolution catalysts,
      hydrogenase enzymes are a source of inspiration. Here, we describe the
      development of a new hybrid material based on a structural and functional [NiFe]
      hydrogenase model complex (NiFe) incorporated into the Zr-based MOF PCN-777. The
      bulk NiFe@PCN-777 material was synthesized by simple encapsulation.
      Characterization by solid-state NMR and IR spectroscopy, SEM-EDX, ICP-OES, and
      gas adsorption confirmed the inclusion of the guest. FTO-supported thin films of
      the NiFe@PCN-777 composite were obtained by electrophoretic deposition of the
      bulk material and characterized by SEM-EDX, ICP-OES, and cyclic voltammetry. The
      average surface concentration of electroactive NiFe catalyst in the film was
      found to be ~9.6 * 10-10 mol cm-2, implying that a surprisingly high fraction
      (37%) of NiFe units incorporated in the MOF are electroactive. By cyclic
      voltammetry, we showed that NiFe maintains its electrocatalytic capabilities for
      H+ reduction inside the MOF cavities, even if under controlled-potential
      electrolysis conditions the activity of NiFe cannot be discerned from that of
      free PCN-777 and FTO.

PMID- 29193980
TI  - A Randomized, Multicenter, Double-Blind, Study to Evaluate the Safety and
      Efficacy of Estradiol Vaginal Cream 0.003% in Postmenopausal Women with Vaginal
      Dryness as the Most Bothersome Symptom.
AB  - BACKGROUND: Vulvovaginal atrophy (VVA) is characterized by vaginal/vulvar
      dryness, irritation, dyspareunia, or dysuria. The objective of this study was to
      examine the efficacy and safety of a very low-dose estradiol vaginal cream
      (0.003%) applied twice per week in postmenopausal women with VVA-related vaginal
      dryness. MATERIALS AND METHODS: In this phase 3, randomized, double-blind,
      placebo-controlled, multicenter study, postmenopausal women with moderate-severe
      vaginal dryness as the most bothersome VVA symptom were randomized (1:1) to
      estradiol cream 0.003% (15 MUg estradiol; 0.5 g cream) or placebo (0.5 g cream).
      Treatments were applied vaginally once daily for 2 weeks followed by two
      applications/week for 10 weeks. Coprimary outcomes were changes in severity of
      vaginal dryness, percentage of vaginal superficial and parabasal cells, and
      vaginal pH at final assessment. Additional outcomes comprised changes in severity
      of other VVA signs and symptoms. Adverse events (AEs) were assessed. RESULTS: Of
      the 576 randomized participants, most were white and had an average age of 59
      years. At final assessment, estradiol reduced vaginal dryness severity, decreased
      vaginal pH, increased superficial cell percentage, and decreased parabasal cell
      percentage versus placebo (p <= 0.05, all). Estradiol also reduced vaginal
      dryness severity at Weeks 4-12 and dyspareunia at Week 8 versus placebo (p <=
      0.05, all). Improvements in vaginal/vulvar irritation/itching severity and
      dysuria were similar between estradiol and placebo. Estradiol had comparable
      rates of treatment-emergent AEs to placebo. No deaths occurred. CONCLUSIONS: Very
      low-dose estradiol vaginal cream (0.003%) dosed twice weekly is an effective and
      well-tolerated treatment for VVA symptoms and dryness associated with menopause.

PMID- 29193979
TI  - When Enough Is Enough: Decision Criteria for Moving a Known Drug into Clinical
      Testing for a New Indication in the Absence of Preclinical Efficacy Data.
AB  - Many animal models of disease are suboptimal in their representation of human
      diseases and lack of predictive power in the success of pivotal human trials. In
      the context of repurposing drugs with known human safety, it is sometimes
      appropriate to conduct the "last experiment first," that is, progressing directly
      to human investigations. However, there are not accepted criteria for when to
      proceed straight to humans to test a new indication. We propose a specific set of
      criteria to guide the decision-making around when to initiate human proof of
      principle without preclinical efficacy studies in animal models. This approach
      could accelerate the transition of novel therapeutic approaches to human
      applications.

PMID- 29193981
TI  - The Relationship between Structure-Related Food Parenting Practices and
      Children's Heightened Levels of Self-Regulation in Eating.
AB  - BACKGROUND: Food parenting practices influence children's eating behaviors and
      weight status. Food parenting practices also influence children's self-regulatory
      abilities around eating, which has important implications for children's eating
      behaviors. The purpose of the following study is to examine use of structure
      related food parenting practices and the potential impact on children's ability
      to self-regulate energy intake. METHODS: Parents (n = 379) of preschool age
      children (M = 4.10 years, SD = 0.92) were mostly mothers (68.6%), Non-White
      (54.5%), and overweight/obese (50.1%). Hierarchical Multiple Regression was
      conducted to predict child self-regulation in eating from structure-related food
      parenting practices (structured meal setting, structured meal timing, family meal
      setting), while accounting for child weight status, parent age, gender, BMI,
      race, and yearly income. RESULTS: Hierarchical Multiple Regression results
      indicated that structure-related feeding practices (structured meal setting and
      family meal setting, but not structured meal timing) are associated with
      children's heightened levels of self-regulation in eating. Models examining the
      relationship within children who were normal weight and overweight/obese
      indicated the following: a relationship between structured meal setting and
      heightened self-regulation in eating for normal-weight children and a
      relationship between family meal setting and heightened self-regulation in eating
      for overweight/obese children. CONCLUSIONS: Researchers should further
      investigate these potentially modifiable parent feeding behaviors as a protective
      parenting technique, which possibly contributes to a healthy weight development
      by enhancing self-regulation in eating.

PMID- 29193983
TI  - Characterization of Departures from Regulatory Requirements Identified During
      Inspections Conducted by the US Federal Select Agent Program, 2014-15.
AB  - We studied departures from regulatory requirements identified on US Federal
      Select Agent Program (FSAP) inspections to increase transparency regarding
      biosafety and security risk at FSAP-regulated entities and identify areas for
      programmatic improvement. Regulatory departures from inspections led by Centers
      for Disease Control and Prevention inspectors during 2014-15 were grouped into
      "biosafety," "security," and "other" observation categories and assigned a risk
      level and score reflecting perceived severity. The resulting 2,267 biosafety (n =
      1,153) and security (n = 1,114) observations from 296 inspections were analyzed
      by frequency and risk across entity and inspection characteristics. The greatest
      proportion of biosafety observations involved equipment and facilities (28%), and
      the greatest proportion of security observations involved access restrictions
      (33%). The greatest proportion of higher-risk observations for biosafety were
      containment issues and for security were inventory discrepancies. Commercial
      entities had the highest median cumulative risk score per inspection (17),
      followed by private (13), academic (10), federal government (10), and nonfederal
      government (8). Maximum containment (BSL-4) inspections had higher median
      biosafety risk per inspection (13) than other inspections (5) and lower security
      risk (0 vs 4). Unannounced inspections had proportionally more upper risk level
      observations than announced (biosafety, 21% vs 12%; security, 18% vs 7%).
      Possessors of select agents had higher median biosafety risk per inspection (6)
      than nonpossessors (4) and more upper risk level security observations (10% vs
      0%). Programmatic changes to balance resources according to entity risk may
      strengthen FSAP oversight. Varying inspection methods by select agent possession
      and entity type, and conducting more unannounced inspections, may be beneficial.

PMID- 29193984
TI  - Population-Based Study to Determine the Health System Costs of Using the 21-Gene
      Assay.
AB  - Purpose The 21-gene assay Oncotype Dx (Genomic Health, Redwood City, CA) test is
      used to aid the decision about chemotherapy in patients with hormone receptor
      positive breast cancer who received endocrine therapy. Economic studies to
      support test adoption used decision-analytic models with assumptions and data
      derived from disparate sources. The objective was to evaluate whether the 21-gene
      assay test resulted in an overall cost expense or saving to the health system.
      Patients and Methods One thousand participants enrolled in a field evaluation
      study, were linked to population-level health system administrative databases,
      and were observed for 20 months. The cost for the cohort, which included the cost
      of the test, subsequent treatments received, and health care encounters, was
      determined. The cost in the absence of the test was compared with the pretest
      recommendation about chemotherapy from the field study for a base case and under
      scenarios that reflected different adjuvant chemotherapy use. Overall health
      system costs and incremental costs were calculated. Results The 21-gene assay
      resulted in a net decrease in chemotherapy use of 23%. For the base case
      incremental analysis, the actual overall health system cost of this cohort,
      including the cost of 21-gene assay, was $29.2 million compared with $26.2
      million in the absence of the test-an increase of $3.1 million. For three of the
      four scenario analyses, the actual overall cost to the health system exceeded the
      estimated cost in the absence of the test. Results showed that, when at least
      half of the population received adjuvant chemotherapy, the cost increased to
      $30.2 million. Conclusion The use of real-world administrative data showed that,
      despite lower rates of chemotherapy use, the 21-gene assay test results in an
      overall incremental cost to the health care system in the short-term under most
      assumptions.

PMID- 29193982
TI  - Biodosimetry: A Future Tool for Medical Management of Radiological Emergencies.
AB  - With the threat of future radiological or nuclear events, there is a need to
      model and develop new medical countermeasures for managing large-scale population
      exposures to radiation. The field of radiation biodosimetry has advanced far
      beyond its original objectives to identify new methodologies to quantitate
      unknown levels of radiation exposure that may be applied in a mass screening
      setting. New research in the areas of genomics, proteomics, metabolomics,
      transcriptomics, and electron paramagnetic resonance (EPR) applications have
      identified novel biological indicators of radiation injury from a diverse array
      of biological sample materials, and studies continue to develop more advanced
      models of radiation exposure and injury. In this article, we identify the urgent
      need for new biodosimetry assessment technologies, describe how biodosimetry
      diagnostics work in the context of a broad range of radiation exposure types and
      scenarios, review the current state of the science, and assess how well
      integrated biodosimetry resources are in the national radiological emergency
      response framework.

PMID- 29193986
TI  - A Study on the Theory of Mind Deficits and Delusions in Schizophrenic Patients.
AB  - PURPOSE: This study was conducted to find differences between patients with
      schizophrenia and healthy control group in ToM and to examine relationships among
      intelligence, ToM, and delusion in patients with schizophrenia. METHODS: Data was
      collected from 50 patients of schizophrenia and 32 healthy subjects. Participants
      were given the psychological test form with structured questionnaire. The SPSS
      22.0 program was used for t-test, ANCOVA, and, Pearson's Correlation.
      Measurements used for this study were Korean-Wechsler intelligence scale, three
      types of Theory of Mind test (Hinting task, False belief task, and Emotional
      attribution test), and Peters delusion inventory. RESULTS: Performances of the
      ToM and intelligence in patients were lower than healthy controls. After
      controlling the impact of IQ, education level, and age, there was a difference
      between patients and healthy controls on the performance of the Hinting task
      (F(1,83) = 10.03, p =.002). Correlation analysis showed that the score of false
      belief task was correlated with delusion (r = -.360, p <.01) and intelligence (r
      =.449, p <.01). The emotional attribution task was correlated with intelligence
      (r = 0.309, p <.05). CONCLUSIONS: Through the finding of this study, theory of
      mind is highly recommended as a new target factor considering to develop nursing
      interventions for schizophrenia.

PMID- 29193988
TI  - Presidential Address of the American Orthopaedic Society for Sports Medicine: Why
      AOSSM? Diversity, Teamwork, and Passion.

PMID- 29193985
TI  - Initial germ cell to somatic cell ratio impacts the efficiency of SSC expansion
      in vitro.
AB  - : Spermatogonial Stem Cell (SSC) expansion in vitro remains a major challenge in
      efforts to preserve fertility among pubertal cancer survivor boys. The current
      study focused on innovative approaches to optimize SSC expansion. Six- to eight
      week-old CD-1 murine testicular samples were harvested by mechanical and
      enzymatic digestion. Cell suspensions were incubated for differential plating
      (DP). After DP, we established two experiments comparing single vs. repetitive DP
      (S-DP and R-DP, respectively) until passage 2 (P2) completion. Each experiment
      included a set of cultures consisting of 5 floating-to-attached cell ratios (5,
      10, 15, 20, and 25) and control cultures containing floating cells only. We found
      similar cell and colony count drops during P0 in both S- and R-DP. During P2,
      counts increased in S-DP in middle ratios (10, 15, and especially 20) relative to
      low and high ratios (5 and 25, respectively). Counts dropped extensively in R-DP
      after passage 2. The superiority of intermediate ratios was demonstrated by
      enrichment of GFRalpha1 by qPCR. The optimal ratio of 20 in S-DP contained
      significantly increased proportions of GFRalpha1-positive cells (25.8+/-5.8%) as
      measured by flow cytometry compared to after DP (1.9+/-0.7%, p<0.0001), as well
      as positive immunostaining for GFRalpha1 and UTF1, with rare Sox9-positive cells.
      This is the first report of the impact of initial floating-to-attached cell
      ratios on SSC proliferation in vitro. ABBREVIATIONS: SSC: spermatogonial stem
      cells; DP: differential plating; NOA: non-obstructive azoospermia; MACS: magnetic
      activated cells sorting; FACS: fluorescence-activated cells sorting.

PMID- 29193990
TI  - Society News and Announcements.

PMID- 29193989
TI  - The Critical Reader-Reliability.

PMID- 29193991
TI  - Diplopia after Strabismus Surgery.
AB  - Diplopia is a disappointing and, at times, unanticipated consequence of what
      might otherwise be considered anatomically successful strabismus surgery. In this
      study, we review the existing literature regarding diplopia after strabismus
      surgery in the context of the senior author's experience. We divide postoperative
      diplopia types into cases that occur in the setting of normal binocular vision
      (or "normal" suppression) vs. cases that are the consequence of rare or anomalous
      sensorial adaptations. We then discuss how to identify patients at greatest risk
      based on history and preoperative testing, and we offer strategies for managing
      these sometimes-challenging cases.

PMID- 29193992
TI  - TLRs/NLRs: Shaping the landscape of host immunity.
AB  - Innate immune system provides the first line of defense against pathogenic
      organisms. It has a varied and large collection of molecules known as pattern
      recognition receptors (PRRs) which can tackle the pathogens promptly and
      effectively. Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are members
      of the PRR family that recognize pathogen associated molecular patterns (PAMPs)
      and play pivotal roles to mediate defense against infections from bacteria,
      fungi, virus and various other pathogens. In this review, we discuss the critical
      roles of TLRs and NLRs in the regulation of host immune-effector functions such
      as cytokine production, phagosome-lysosome fusion, inflammasome activation,
      autophagy, antigen presentation, and B and T cell immune responses that are known
      to be essential for mounting a protective immune response against the pathogens.
      This review may be helpful to design TLRs/NLRs based immunotherapeutics to
      control various infections and pathophysiological disorders.

PMID- 29193993
TI  - Effects of Anthropometric Variables and Seat Height on Automobile Drivers'
      Preferred Posture With the Presence of the Clutch.
AB  - Objective The effects of seat height and anthropometric dimensions on drivers'
      preferred postures were investigated using a multiadjustable vehicle mock-up with
      a large number of adjustments and extended ranges. Background Many studies have
      been conducted on preferred driving posture under different test conditions
      showing mixed and even contradictory findings. No studies thus far have
      considered the clutch and compared Chinese and European drivers. Method Four seat
      height conditions were tested: free and three imposed heights (250, 300, and 350
      mm). Sixty-one subjects (40 French-born and 21 Chinese-born) participated in the
      experiment, covering a large range of stature and sitting height-to-stature
      ratio. The RAMSIS kinematic model was used to reconstruct postures, and main
      intersegmental angles were extracted for characterizing posture. Results Under
      the free seat height condition, no significant differences in preferred
      intersegmental angles were observed between different participant groups. Seat
      height mainly affected trunk-thigh angle, whereas it had almost no effect on
      trunk orientation and other intersegmental angles. Chinese participants sat more
      forward in the seat, leading to a more opened trunk-thigh angle and a more
      reclined trunk. Conclusions Results suggest that intersegmental angles of
      preferred posture are not dependent on anthropometric dimensions, although
      shorter drivers prefer a slightly less reclined trunk. Self-selected driving
      posture results from a compromise between maintaining the intersegmental angles
      in one's preferred range and a preferred trunk orientation in space. Applications
      The findings contribute to a better understanding of preferred driving postures
      and would be helpful for improving vehicle interior design.

PMID- 29193994
TI  - Gender Diversity in Nursing.

PMID- 29193997
TI  - Predicting Airport Screening Officers' Visual Search Competency With a Rapid
      Assessment.
AB  - Objective The study's objective was to assess a new personnel selection and
      assessment tool for aviation security screeners. A mobile app was modified to
      create a tool, and the question was whether it could predict professional
      screeners' on-job performance. Background A variety of professions (airport
      security, radiology, the military, etc.) rely on visual search performance-being
      able to detect targets. Given the importance of such professions, it is necessary
      to maximize performance, and one means to do so is to select individuals who
      excel at visual search. A critical question is whether it is possible to predict
      search competency within a professional search environment. Method Professional
      searchers from the USA Transportation Security Administration (TSA) completed a
      rapid assessment on a tablet-based X-ray simulator (XRAY Screener, derived from
      the mobile technology app Airport Scanner; Kedlin Company). The assessment
      contained 72 trials that were simulated X-ray images of bags. Participants
      searched for prohibited items and tapped on them with their finger. Results
      Performance on the assessment significantly related to on-job performance
      measures for the TSA officers such that those who were better XRAY Screener
      performers were both more accurate and faster at the actual airport checkpoint.
      Conclusion XRAY Screener successfully predicted on-job performance for
      professional aviation security officers. While questions remain about the
      underlying cognitive mechanisms, this quick assessment was found to significantly
      predict on-job success for a task that relies on visual search performance.
      Application It may be possible to quickly assess an individual's visual search
      competency, which could help organizations select new hires and assess their
      current workforce.

PMID- 29193996
TI  - Genome-wide association study of rice grain width variation.
AB  - Seed size is variable within many plant species, and understanding the underlying
      genetic factors can provide insights into mechanisms of local environmental
      adaptation. Here we make use of the abundant genomic and germplasm resources
      available for rice (Oryza sativa) to perform a large-scale genome-wide
      association study (GWAS) of grain width. Grain width varies widely within the
      crop and is also known to show climate-associated variation across populations of
      its wild progenitor. Using a filtered dataset of >1.9 million genome-wide SNPs in
      a sample of 570 cultivated and wild rice accessions, we performed GWAS with two
      complementary models, GLM and MLM. The models yielded 10 and 33 significant
      associations, respectively, and jointly yielded seven candidate locus regions,
      two of which have been previously identified. Analyses of nucleotide diversity
      and haplotype distributions at these loci revealed signatures of selection and
      patterns consistent with adaptive introgression of grain width alleles across
      rice variety groups. The results provide a 50% increase in the total number of
      rice grain width loci mapped to date and support a polygenic model whereby grain
      width is shaped by gene-by-environment interactions. These loci can potentially
      serve as candidates for studies of adaptive seed size variation in wild grass
      species.

PMID- 29193998
TI  - Relation Among Anxiety and Family Burden in Primary First-Degree Caregivers of
      Outpatients with Mental Disorders in Turkey.
AB  - The aim of this study was to determine the relation among anxiety and family
      burden in primary first-degree relative caregivers of outpatients with mental
      disorders in Turkey. Data were collected with patients' primary first-degree
      relative caregivers via the Information Form, Beck Anxiety Inventory (BAI), and
      Perceived Family Burden Scale (PFBS). In all, 481 caregivers (325 women and 156
      men) participated in this study. Based on this study's results, primary
      caregivers of patients with mental disorders had a moderate level anxiety, and as
      anxiety increased, family burden also increased. Those results suggest that
      mental health nurses should plan interventions not only for patients, but also
      for their family member or their caregivers to decrease anxiety level.

PMID- 29193995
TI  - Beck Depression Inventory-II: Factor Analyses with Three Groups of Midlife Women
      of African Descent in the Midwest, the South, and the U.S. Virgin Islands.
AB  - This research encompasses a factor analysis of the Beck Depression Inventory-II
      (BDI-II), which involves three groups of midlife women of African descent who
      reside in the Midwest, the South, and the U.S. Virgin Islands. The purpose of the
      study was to determine the factor structure of the BDI-II when administered to a
      sample of women aged 40-65 of African descent who reside in the three distinct
      geographical regions of the United States. A correlational, descriptive design
      was used, and 536 women of African descent were invited to participate in face-to
      face interviews that transpired in community settings. Results of the factor
      analysis revealed a two-factor explanation. Factor one included symptoms such as
      punishment feelings and pessimism (cognitive), and the second factor included
      symptoms such as tiredness and loss of energy (somatic-affective). The
      application of the Beck Depression Inventory-II among the three groups of women
      generated specific information about each group and common findings across the
      groups. Knowledge gained from the research could help to guide specific
      intervention programs for the three groups of women, and explicate the common
      approaches that could be used for the three groups.

PMID- 29193999
TI  - Nursing and the Emergence of Egoless Care: A Discussion on Social Engineering in
      Mental Health.
AB  - The narrowing of the diverse fields of psychiatry to just the single dimension of
      the biomedical model has resulted in a situation where professions with a focus
      on curing (psychiatrists and psychologists) are favoured over those with a focus
      on caring and encouraging near communities to care for each other (nurses). The
      social engineering of mental problems leads to a state of helplessness. This
      paper contributes to an understanding of the barriers to utilise the social
      resources of people with mental health problems and argues for forms of "indirect
      social engineering" and "egoless care," and, ultimately, a rediscovery of
      nursing, using the mental health care in the Netherlands as a case study.

PMID- 29194000
TI  - Time dependent reduction in platelet aggregation using the multiplate analyser
      and hirudin blood due to platelet clumping.
AB  - The Multiplate is a popular instrument that measures platelet function using
      whole blood. Potentially considered a point of care instrument, it is also used
      by hemostasis laboratories. The instrument is usually utilized to assess
      antiplatelet medication or as a screen of platelet function. According to the
      manufacturer, testing should be performed within 0.5-3 hours of blood collection,
      and preferably using manufacturer provided hirudin tubes. We report time
      associated reduction in platelet aggregation using the Multiplate and hirudin
      blood collection tubes, for all the major employed agonists. Blood for Multiplate
      analysis was collected into manufacturer supplied hirudin tubes, and 21
      consecutive samples assessed using manufacturer supplied agonists (ADP,
      arachidonic acid, TRAP, collagen and ristocetin), at several time-points post
      sample collection within the recommended test time period. Blood was also
      collected into EDTA as a reference method for platelet counts, with samples
      collected into sodium citrate and hirudin used for comparative counts. All
      platelet agonists showed a diminution of response with time. Depending on the
      agonist, the reduction caused 5-20% and 22-47% of responses initially in the
      normal reference range to fall below the reference range at 120min and 180min,
      respectively. Considering any agonist, 35% and 67% of initially "normal"
      responses became 'abnormal' at 120 min and 180 min, respectively. Platelet counts
      showed generally minimal changes in EDTA blood, but were markedly reduced over
      time in both citrate and hirudin blood, with up to 40% and 60% reduction,
      respectively, at 240 min. The presence of platelet clumping (micro-aggregate
      formation) was also observed in a time dependent manner, especially for hirudin.
      In conclusion, considering any platelet agonist, around two-thirds of samples
      can, within the recommended 0.5-3 hour testing window post-blood collection,
      yield a reduction in platelet aggregation that may lead to a change in
      interpretation (i.e., normal to reduced). Thus, the stability of Multiplate
      testing can more realistically be considered as being between 30-120 min of blood
      collection for samples collected into hirudin.

PMID- 29194002
TI  - Auranofin, a thioredoxin reductase inhibitor, causes platelet death through
      calcium overload.
AB  - Platelets are central to normal hemostasis and must be tightly controlled to
      prevent thrombosis. However, drug treatments that also affect platelets could
      lead to unwanted side effects on hemostasis or thrombosis. In this study, the
      effect of auranofin on platelets was tested. Auranofin, a gold-based thioredoxin
      reductase (TRXR) inhibitor, has been previously used in arthritis. Recently,
      auranofin and other inhibitors of the thioredoxin system have been proposed as
      novel anti-cancer therapies. TRXR is an important part of the antioxidant
      defenses in many cells that maintain intracellular proteins in their reduced
      state. TRXR activity in platelets could be completely inhibited by auranofin.
      Auranofin-treated platelets showed several features of cell death, including the
      inability to aggregate in response to thrombin, leakage of cytosolic lactate
      dehydrogenase, and surface exposure of procoagulant phosphatidylserine. Auranofin
      increased platelet reactive oxygen species production and intracellular calcium
      concentration. DTT, a sulfydyl reducing agent, and BAPTA-AM, which chelates
      intracellular calcium, prevented auranofin-induced phosphatidylserine exposure.
      These data suggest that TRXR is an important part of the platelet antioxidant
      defense. TRXR inhibition by auranofin triggers oxidative stress and disrupts
      intracellular calcium homeostasis, leading to platelet necrosis. The use of
      auranofin or other TRXR inhibitors could therefore lead to unwanted side effects.

PMID- 29194001
TI  - Racial Disparities in Clinically Significant Prostate Cancer Treatment: The
      Potential Health Information Technology Offers.
AB  - PURPOSE: Black men are more likely to die as a result of prostate cancer than
      white men, despite effective treatments that improve survival for clinically
      significant prostate cancer. We undertook this study to identify gaps in prostate
      cancer care quality, racial disparities in care, and underlying reasons for
      poorer quality care. METHODS: We identified all black men and random age-matched
      white men with Gleason scores >= 7 diagnosed between 2006 and 2013 at two urban
      hospitals to determine rates of treatment underuse. Underuse was defined as not
      receiving primary surgery, cryotherapy, or radiotherapy. We then interviewed
      treating physicians about the reasons for underuse. RESULTS: Of 359 black and 282
      white men, only 25 (4%) experienced treatment underuse, and 23 (92%) of these
      were black. Most (78%) cases of underuse were due to system failures, where
      treatment was recommended but not received; 38% of these men continued receiving
      care at the hospitals. All men with treatment underuse due to system failures
      were black. CONCLUSION: Treatment rates of prostate cancer are high. Yet, racial
      disparities in rates and causes of underuse remain. Only black men experienced
      system failures, a type of underuse amenable to health information technology
      based solutions. Institutions are missing opportunities to use their health
      information technology capabilities to reduce disparities in cancer care.

PMID- 29194003
TI  - Mediating effect of deviant peers on the relationship between sensation seeking
      and lifetime smoking among high school students.
AB  - BACKGROUND: Despite the greater risk of lifetime smoking among high sensation
      seekers, it is difficult to change a sensation seeking tendency through
      interventions. Therefore, it is important to identify a modifiable factor
      mediating the link between these two conditions in order to weaken or disconnect
      the association. OBJECTIVES: Based on the literature, deviant peers may play a
      pivotal role in explaining this association. Thus, we aimed to investigate the
      mediating effect of deviant peers on the association between sensation seeking
      and lifetime smoking among Korean adolescents. METHODS: We analyzed secondary
      data obtained from 876 high school students. Approximately 51% of the
      participants were male. In order to investigate the mediating effect of deviant
      peers after controlling for 16 factors, we tested an indirect effect in a simple
      mediation model using the PROCESS macro, which is a regression-based approach.
      RESULTS: We found a significant total effect of sensation seeking on lifetime
      smoking: greater risk of lifetime smoking among high sensation seekers. In
      addition, we found a significant mediating effect of deviant peers on the
      association between the two conditions. Specifically, higher sensation seeking
      successfully predicted a greater number of deviant peers, which, in turn,
      successfully predicted greater risk of lifetime smoking. CONCLUSION: Given
      difficulties in directly changing levels of sensation seeking and the significant
      mediating effect of deviant peers on the association between the two conditions,
      prevention strategies focusing on peers may be advantageous for high sensation
      seekers in reducing their risk of lifetime smoking in adolescence.

PMID- 29194004
TI  - Featured Canadian Research on Child, Adolescent, and Young Adult Psychiatry.

PMID- 29194005
TI  - Patient Characteristics, Length of Stay, and Functional Improvement for
      Schizophrenia Spectrum Disorders: A Population Study of Inpatient Care in Ontario
      2005 to 2015.
AB  - OBJECTIVES: Schizophrenia and associated illnesses account for a large proportion
      of mental illness burden and health care expenditures, with the majority of
      expense involving inpatient care. To date, the literature exploring factors
      associated with length of stay (LOS) and functional improvement during inpatient
      care is underdeveloped. In response, this study examined the association between
      patient characteristics, LOS, and functional improvement using Ontario Mental
      Health Reporting System (OMHRS) data from 2005 to 2015. METHODS: The associations
      of patient characteristics (including key demographics, psychosocial variables,
      reasons for admission, and service use history) and 2 outcome measures (LOS and
      Global Assessment of Functioning [GAF]) were analysed with generalised linear
      mixed modelling (GLMM). From 2005 to 2015, a total of 48,498 episodes for
      distinct patients from 18 psychiatric hospitals and 57 general hospitals in
      Ontario were included. RESULTS: For psychiatric and general hospitals, mean LOS
      was 96.6 and 20.5 days, and mean GAF improvement was 14.8 and 16.1, respectively.
      The majority of associations probed demonstrated a high degree of significance
      with similar patterns across general and tertiary facility contexts. Older age
      and more recent readmission following a psychiatric discharge were associated
      with longer LOS and less GAF improvement. Recent experience of adverse life
      events and substance misuse were associated with shorter LOS. CONCLUSIONS: While
      the findings of this exploratory cross-sectional analysis will require further
      inquiry with respect to validity and reliability, they suggest that a different
      service pathway is likely required for individuals with greater psychosocial
      challenge and extensive service use histories.

PMID- 29194006
TI  - Retention of functional characteristics of glutathione-S-transferase and lactate
      dehydrogenase-A in fusion protein.
AB  - A paradigm shift toward fusion proteins to render multiple functionalities and
      applications on a single platform has been incurred in enzyme based diagnosis.
      Herein, we report development and systematic characterizations of glutathione-S
      transferase (GST) and human lactate dehydrogenase A (hLDHA) in a fusion protein
      (GST-hLDHA) to achieve functional activities of GST and hLDHA simultaneously. The
      GST-pGEX-4T-2 vector system was used for cloning and purification of hLDHA,
      utilizing the affinity based interaction between GST and GSH in column
      chromatography. Bacterially purified protein was subjected to the Western blot
      analysis and structural analysis by circular dichroism spectroscopy, which
      revealed intact structural framework of the fusion construct. Kinetic
      characterization of the fusion GST-hLDHA protein toward GSH and NADH, suggested
      retention of functional activities of GST and hLDHA in fused protein as indicated
      by the kinetic parameters km and kcat/km. Further analysis of effect of
      temperature and pH on GST-hLDHA activity revealed maximum activity around human
      physiological conditions (37 degrees C and pH 8). Preservation of the structural
      and functional characteristics of the fusion enzyme paves the way for potential
      application for the detection of NADH and GSH in conjunction as biomarkers for
      cancer diagnosis.

PMID- 29194007
TI  - Product review on the Anti-PD-L1 antibody atezolizumab.
AB  - Immunotherapy as a therapeutic strategy has seized the narrative throughout
      clinical oncology over the past few years. Once considered a niche treatment for
      rare cancers, immunotherapy has quickly emerged as the standard of care for many
      common cancer types. The remarkable rise is largely due to the development of
      novel checkpoint inhibitors, specifically, antibodies targeting PD-1 and PD-L1.
      Offering promising efficacy with a favorable toxicity profile, these agents have
      been approved for use in several malignancies and are under investigation for
      many more. One of the more appealing features is the chance for meaningful,
      durable response - uncharacteristic for most cancer therapies. Atezolizumab is a
      humanized IgG1 monoclonal antibody that targets PD-L1. Atezolizumab has been
      approved for use in the treatment of advanced non-small cell lung cancer (NSCLC)
      and bladder cancer and has shown promising activity in several other types of
      cancer. Here, we provide a product review for atezolizumab.

PMID- 29194008
TI  - Removal of excess nutrients by Australian zeolite during anaerobic digestion of
      swine manure.
AB  - The objective of this study was to investigate the feasibility of using natural
      and NaCl-treated Australian zeolites to simultaneously remove excess nutrients
      from anaerobically digested swine manure. Ion adsorption and desorption
      properties of Australian zeolite during the anaerobic digestion of swine manure
      were investigated. Two experiments were conducted: the first was an adsorption
      experiment with multi-component solutions that corresponded with the ionic
      composition of swine manure digestates. The second experiment determined the
      effects of zeolite dose rates during anaerobic digestion of swine manure on the
      removal of N, P and K from solution. Adsorption isotherms confirmed selectivity
      for K+ over NH4+ by Australian natural and sodium zeolites. Therefore, NH4+
      removal was considerably reduced when there was simultaneous K+ uptake. Natural
      zeolite desorbed more Ca2+ during K+ and NH4+ adsorption than sodium zeolite. The
      ion exchange reaction was independent of the presence of P. P removal was very
      dependent on the pH of the medium. Natural Australian zeolite was shown to be a
      potential sorbent for the removal of NH4+, K+ and P during the anaerobic
      digestion of swine manure. However, the application of high concentrations of
      zeolite at higher pH values (> 7.5) might not be appropriate for anaerobic
      digestion, because zeolite desorbed more Ca2+ ions into the solution at the
      higher doses of zeolite and then availability of P for microbial growth might be
      reduced as a result of PO43- precipitation with Ca2+ at the higher pH.

PMID- 29194009
TI  - Bias in Radiology: The How and Why of Misses and Misinterpretations.
AB  - Medical errors are a leading cause of morbidity and mortality in the medical
      field and are substantial contributors to medical costs. Radiologists play an
      integral role in the diagnosis and care of patients and, given that those in this
      field interpret millions of examinations annually, may therefore contribute to
      diagnostic errors. Errors can be categorized as a "miss" when a primary or
      critical finding is not observed or as a "misinterpretation" when errors in
      interpretation lead to an incorrect diagnosis. In this article, the authors
      describe the cognitive causes of such errors in diagnostic medicine, specifically
      in radiology. Recognizing the cognitive processes that radiologists use while
      interpreting images should improve one's awareness of the inherent biases that
      can impact decision making. The authors review the common biases that impact
      clinical decisions, as well as strategies to counteract or minimize the potential
      for misdiagnosis. System-level processes that can be implemented to minimize
      cognitive errors are reviewed, as well as ways to implement personal changes to
      minimize cognitive errors in daily practice. (c)RSNA, 2017.

PMID- 29194010
TI  - Impact of serogroup A meningococcal conjugate vaccine for Africa.
AB  - The introduction of a serogroup A meningococcal conjugate vaccine in the African
      meningitis belt has been a remarkable success. Meningitis due to the serogroup A
      meningococcus, previously responsible for most epidemics, has fallen by 99% in
      vaccinated countries. Success must, however, not distract from the continuing
      burden of meningitis in this region of Africa. The number of all meningitis
      epidemics at health district level has fallen by 60% following vaccination, but
      epidemics due to other meningococcal serogroups continue and may be increasing.
      The introduction of low cost multivalent conjugate vaccines must be given high
      public health priority.

PMID- 29194011
TI  - Rapid Source-Control Laparotomy: Is There a Mortality Benefit in Septic Shock?
AB  - BACKGROUND: In the 1990s, damage control laparotomy (DCL) became a proved
      approach to treat intra-abdominal injuries caused by trauma. In the ensuing two
      decades, this approach has been applied to non-traumatic abdominal processes as
      well. Although the benefits of DCL are clear, the benefit of rapid source-control
      laparotomy (RSCL) for non-traumatic abdominal diseases is much less clear.
      However, two recent cohort analyses identified significant increases in the
      mortality rate with RCSL compared with primary fascial closure (PFC). The purpose
      of this study was to assess the efficacy of RSCL in patients with septic shock.
      METHODS: The 2015 National Surgical Quality Improvement Project (NSQIP) database
      was queried for 11 International Statistical Classifications of Diseases (ICD)-10
      codes associated with septic shock. Collected data included age, gender, body
      mass index (BMI), wound class, American Society of Anesthesiologists (ASA) class,
      operative time, number of risk factors, and presence or absence of post-operative
      pneumonia. The risk factors were diabetes mellitus, alcohol or tobacco abuse,
      blood dyscrasias, disseminated cancer, and cardiac, gastrointestinal, pulmonary,
      hepatobiliary, or renal dysfunction. The primary outcomes were rate of re
      operation, prevalence of post-operative pneumonia, hospital length of stay (LOS),
      and death by 30 days. RESULTS: The RSCL and PFC cohorts were each comprised of 56
      patients matched for propensity scores for ICD-10 code. There were no significant
      differences in wound or ASA class, BMI, gender, or number of risk factors between
      the two cohorts. The operative time for RSCL was significantly shorter than for
      PFC (median 84 vs. 128 min, respectively; p = 0.002). There was no significant
      difference in re-operation rate, prevalence of post-operative pneumonia, LOS, or
      mortality rate between the two cohorts. CONCLUSIONS: Although this analysis
      showed no clear advantage to RSCL in the management of septic shock, it may be a
      means to salvage certain patients. The best way to assess the relative value of
      RSCL is a prospective trial.

PMID- 29194012
TI  - Funding vaccines for emerging infectious diseases.
AB  - Immunization has played a large role in substantially reducing the infected and
      death tolls from infectious diseases. In the case of emerging diseases, the
      identity of the pathogen responsible, as well as the time and location for the
      next outbreak, cannot be accurately predicted using current means. Coupled with
      disjointed efforts towards the development of vaccines and a lack of funds and
      desire to advance promising products against known emerging pathogens to clinical
      trials, there has been a shortage of approved products ready for emergency use.
      Recent outbreaks have exposed these weaknesses, and the Coalition for Epidemic
      Preparedness Innovations (CEPI) was created in 2016 to address these issues. In
      this commentary, we discuss the establishment of such a global vaccine fund, and
      provide some additional points to consider for stimulating further discussion on
      this comprehensive, ambitious initiative.

PMID- 29194013
TI  - Public policy for meningococcal vaccination.
AB  - On an individual basis, meningococcal disease is consistently shown to be one of
      the most feared potential childhood infections. On a population level, any
      clustering of cases or increase in disease requires proactive health protection
      management, while epidemics can be devastating. It is therefore no surprise that
      developing protective meningococcal vaccines and effective strategies for their
      implementation has been a continuing public health priority for some decades.

PMID- 29194014
TI  - Respiratory syncytial virus seasonality and its implications on prevention
      strategies.
AB  - With maternal and infant vaccines against respiratory syncytial virus (RSV) in
      development, it is timely to consider how the deployment of these vaccines might
      vary according to local RSV disease seasonality. In temperate regions RSV
      infection is predictably limited to a period of 3 to 5 months, while in tropical
      regions disease seasonality is often both more variable and more prolonged.
      Accordingly, in tropical regions a year-round immunisation schedule for both
      maternal and infant immunisation might be appropriate. In contrast, in temperate
      regions the benefit of year-round maternal immunisation would be heavily
      dependent on the duration of protection this provided, potentially necessitating
      a strategy directed at children due to be born in the months immediately prior to
      the RSV season. This review will consider the impact of seasonality on maternal
      and infant immunisation strategies against RSV, and the potential of an
      alternative approach of passive immunisation for all infants immediately prior to
      the RSV season.

PMID- 29194015
TI  - Phytase from Citrobacter koseri PM-7: Enhanced production using statistical
      method and application in ameliorating mineral bioaccessibility and protein
      digestibility of high-phytate food.
AB  - The present study was aimed at enhancing phytase (Phy-Ck) production from
      Citrobacter koseri PM-7 using response surface methodology (RSM) and improving
      the bioaccessibility of minerals (Fe and Zn) and protein digestibility in high
      phytate food using Phy-Ck. A five-variable and three-level central composite
      design of RSM using wheat bran (6.681%, w/v), inoculum level (2.5%, v/v), and
      triton X-100 (0.2%, v/v) resulted in up to 5.57-fold (1.047 U/ml) improvement in
      Phy-Ck yield from C. koseri PM-7 when compared with fermentation media I and II.
      The model was successfully validated in the design space by taking a random set
      of variable combinations. Treatment of high-phytate food with partially purified
      Phy-Ck showed improvement in mineral bioaccessibility maximally for defatted
      sesame flour (DSF) (Fe 45.5%; Zn 50.7%) followed by wheat flour (WF) (Fe 13.5%;
      Zn 14.4%), green gram flour (GGF) (Fe 0.7%; Zn 3.8%) and defatted groundnut flour
      (DGF) (Zn 5.6%). The in vitro protein digestibility (IVPD) of WF increased from
      48.83 to 65.04%, GGF from 45.04 to 57.12%, and DSF from 47.34 to 55.7% after Phy
      Ck treatment.

PMID- 29194016
TI  - Assessment of occupational exposure to asbestos fibers: Contribution of
      analytical transmission electron microscopy analysis and comparison with phase
      contrast microscopy.
AB  - From November 2009 to October 2010, the French general directorate for labor
      organized a large field-study using analytical transmission electron microscopy
      (ATEM) to characterize occupational exposure to asbestos fibers during work on
      asbestos containing materials (ACM). The primary objective of this study was to
      establish a method and to validate the feasibility of using ATEM for the analysis
      of airborne asbestos of individual filters sampled in various occupational
      environments. For each sampling event, ATEM data were compared to those obtained
      by phase-contrast optical microscopy (PCOM), the WHO-recommended reference
      technique. A total of 265 results were obtained from 29 construction sites where
      workers were in contact with ACM. Data were sorted depending on the combination
      of the ACM type and the removal technique. For each "ACM-removal technique"
      combination, ATEM data were used to compute statistical indicators on short, fine
      and WHO asbestos fibers. Moreover, exposure was assessed taking into account the
      use of respiratory protective devices (RPD). As in previous studies, no simple
      relationship was found between results by PCOM and ATEM counting methods. Some
      ACM, such as asbestos-containing plasters, generated very high dust levels, and
      some techniques generated considerable levels of dust whatever the ACM treated.
      On the basis of these observations, recommendations were made to measure and
      control the occupational exposure limit. General prevention measures to be taken
      during work with ACM are also suggested. Finally, it is necessary to continue
      acquiring knowledge, in particular regarding RPD and the dust levels measured by
      ATEM for the activities not evaluated during this study.

PMID- 29194017
TI  - Rhizomucor miehei lipase immobilized on reinforced chitosan-chitin nanowhiskers
      support for synthesis of eugenyl benzoate.
AB  - An alternative environmentally benign support was prepared from chitosan-chitin
      nanowhiskers (CS/CNWs) for covalent immobilization of Rhizomucor miehei lipase
      (RML) to increase the operational stability and recyclability of RML in
      synthesizing eugenyl benzoate. The CS/CNWs support and RML-CS/CNWs were
      characterized using X-ray diffraction, fluorescent microscopy, and Fourier
      transform infrared spectroscopy. Efficiency of the RML-CS/CNWs was compared to
      the free RML to synthesize eugenyl benzoate for parameters: reaction temperature,
      stirring rate, reusability, and thermal stability. Under optimal experimental
      conditions (50 degrees C, 250 rpm, catalyst loading 3 mg/mL), a twofold increase
      in yield of eugenyl benzoate was observed for RML-CS/CNWs as compared to free
      RML, with the former achieving maximum yield of the ester at 62.1% after 5 hr.
      Results demonstrated that the strategy adopted to prepare RML-CS/CNWs was useful,
      producing an improved and prospectively greener biocatalyst that supported a
      sustainable process to prepare eugenyl benzoate. Moreover, RML-CS/CNWs are
      biodegradable and perform esterification reactions under ambient conditions as
      compared to the less eco-friendly conventional acid catalyst. This research
      provides a facile and promising approach for improving activity of RML in which
      the resultant RML-CS/CNWs demonstrated good operational stability for up to eight
      successive esterification cycles to synthesize eugenyl benzoate.

PMID- 29194018
TI  - Customized design and 3D printing of face seal for an N95 filtering facepiece
      respirator.
AB  - Filtering Facepiece Respirator (FFR) is the most common respirator users in the
      health care environment utilize for personal protection from outside particles.
      Comfort and fit are important while wearing an FFR. This paper proposes a novel
      technology to produce customized face seal design for improving the wearing
      comfort and fit of FFR wearers. In order to customize the design of face seals,
      we scanned the faces of three subjects using three-dimensional (3D) laser
      scanning method. A customized face seal for a 3M 8210 N95 FFR for each headform
      was designed using reverse engineering technique. Next, the face seal prototypes
      were fabricated with Acrylonitrile Butadiene Styrene (ABS) plastic using the 3D
      printing method. A force sensing system based on Arduino Uno R3 was developed,
      and the force sensor of this system was inserted between the FFR and headform to
      measure contact pressure. Experimental results showed that the newly designed FFR
      face seal provided the subjects with an improved contact pressure.

PMID- 29194019
TI  - An analysis of factors associated with influenza, pneumoccocal, Tdap, and herpes
      zoster vaccine uptake in the US adult population and corresponding inter-state
      variability.
AB  - Despite longstanding recommendations for routine vaccination against influenza;
      pneumococcal; tetanus, diphtheria, acellular pertussis (Tdap); and herpes zoster
      (HZ) among the United States general adult population, vaccine uptake remains
      low. Understanding factors that influence adult vaccination and coverage
      variability beyond the national level are important steps toward developing
      targeted strategies for increasing vaccination coverage. A retrospective analysis
      was conducted using data from the Behavioral Risk Factor Surveillance System
      (2011-2014). Multivariable logistic regression modeling was employed to identify
      individual factors associated with vaccination (socio-demographics, health
      status, healthcare utilization, state of residence) and generate adjusted
      vaccination coverage and compliance estimates nationally and by state. Results
      indicated that multiple characteristics were consistently associated with a
      higher likelihood of vaccination across all four vaccines, including female sex,
      increased educational attainment, and annual household income. Model-adjusted
      vaccination coverage estimates varied widely by state, with inter-state
      variability for the most recent year of data as follows: influenza (aged >=18
      years) 30.2-49.5%; pneumococcal (aged >=65 years) 64.0-74.7%; Tdap (aged >=18
      years) 18.7-46.6%; and HZ (aged >=60 years) 21.3-42.9%. Model-adjusted compliance
      with age-appropriate recommendations across vaccines was low and also varied by
      state: influenza+Tdap (aged 18-59 years) 7.9-24.7%; influenza+Tdap+HZ (aged 60-64
      years) 4.1-14.4%; and influenza+Tdap+HZ+pneumococcal (aged >=65 years) 3.0-18.3%.
      In summary, after adjusting for individual characteristics associated with
      vaccination, substantial heterogeneity across states remained, suggesting that
      other local factors (e.g. state policies) may be impacting adult vaccines uptake.
      Further research is needed to understand such factors, focusing on differences
      between states with high versus low vaccination coverage.

PMID- 29194020
TI  - Anaerobic detoxification fermentation by Rhodospirillum rubrum for rice straw as
      feed with moderate pretreatment.
AB  - A novel and effective process was put forward for converting rice straw into feed
      by combining diluted acid hydrolysis and ammonization with Rhodospirillum rubrum
      fermentation. After pretreatment with dilute sulfuric or phosphoric acid (1%,
      w/w) at 100 degrees C, materials were subjected to fermentation under several
      gases (N2, CO2, and air) and different light intensities in a 2-L fermentor. The
      key indexes of feed for fermented materials were estimated and several toxic
      substances were investigated during the fermentation. Following sulfuric acid
      treatment, the true protein of rice straw increased from 29 to 143 g kg-1 and the
      crude fiber decreased from 359 to 136 g kg-1 after fermentation at 0.3 L min-1 L
      1 of N2 flow and a light intensity of 3400 lux; and following phosphoric acid
      treatment, the true protein increased by 286% and the crude fiber decreased by
      52% after fermentation at 0.4 L min-1 L-1 of N2 flow and a light intensity of
      3000 lux. Other key contents were also improved for use as feed, and some toxic
      substances (i.e., furfural, hydroxymethylfurfural, acetic acid, phenol, cresol)
      produced by the pretreatments could be removed at low levels during the
      fermentations.

PMID- 29194021
TI  - A retrospective analysis of nickel exposure data at a South African base metal
      refinery.
AB  - This study aimed to analyze historical soluble nickel exposure data from a South
      African base metal refinery and to identify trends in the soluble nickel exposure
      from 1981 until 2014 in the electrowinning department. Exposure data were
      presented in an exposure matrix, which described exposure profiles for both area
      and personal exposures inside two tankhouses. Exposure data were standardized by
      converting total nickel aerosol concentrations to inhalable nickel concentrations
      (correction factor 3.0). One-way analyses of variances (ANOVA) were conducted to
      identify significant differences in log-transformed area and personal exposures
      from 1982 until 2014, and the trends were assessed with linear regression.
      Differences were evaluated in area exposure between sections inside the
      tankhouses, i.e., East, West, and Center bays and in personal exposure between
      occupations, i.e., cell workers, crane drivers, and supervisors. Area exposure in
      Tankhouse 1 declined significantly (p <= 0.0001) between 1982 and 1986 with a
      factor of 29. However, after 1986 no significant downward trend in area exposure
      was evident in Tankhouse 1. Personal exposures in Tankhouse 1 significantly (p <=
      0.0001) decreased with a factor of three between 1991 and 2014. No significant
      trends were evident in area and personal exposure in Tankhouse 2. Downward
      exposure trends were evident in Tankhouse 1 and may be ascribed to the
      implementation of various control measures and process changes, e.g., increasing
      polypropylene bead load. Limited data were available for Tankhouse 2, therefore,
      no trend in exposure could be established. Retrospective analyses may be used to
      identify trends and anomalies in exposure which might not have been identified
      during daily exposure monitoring.

PMID- 29194022
TI  - Resumes en Francais.

PMID- 29194023
TI  - Leveraging Social Capital of Persons With Intellectual Disabilities Through
      Facebook Participation: The Perspectives of Family Members and Direct Support
      Staff.
AB  - This study aimed to understand and describe the views of family members and
      direct support staff regarding the use of Facebook by persons with intellectual
      disability (ID) within the context of social capital. In-depth, semistructured
      interviews conducted with 16 family members and direct support staff of persons
      with ID who use Facebook revealed that most participants favored Facebook use by
      persons with ID for bonding and bridging social capital and for normalization.
      Most participants noted the empowering effect of online activity on persons with
      ID, yet some reported risks and usage difficulties. Although Facebook use
      enhances the well-being of persons with ID, findings highlighted the
      participants' need for formal guidelines regarding social media best-practices
      for people with ID.

PMID- 29194024
TI  - Adapting the Mullen Scales of Early Learning for a Standardized Measure of
      Development in Children With Rett Syndrome.
AB  - Rett Syndrome (RTT) is characterized by severe impairment in fine motor (FM) and
      expressive language (EL) function, making accurate evaluations of development
      difficult with standardized assessm ents. In this study, the administration and
      scoring of the Mullen Scales of Early Learning (MSEL) were adapted to eliminate
      the confounding effects of FM and EL impairments in assessing development. Forty
      seven girls with RTT were assessed with the Adapted-MSEL (MSEL-A), a subset (n =
      30) was also assessed using the Vineland Adaptive Behavior Scales-Second Edition
      (Vineland-II) and a further subset (n = 17) was assessed using an eye-tracking
      version of the MSEL (MSEL-ET). Participants performed better on the visual
      reception (VR) and receptive language (RL) domains compared to the FM and EL
      domains on the MSEL-A. Individual performance on each domain was independent of
      other domains. Corresponding MSEL-A and Vineland-II domains were significantly
      correlated. The MSEL-ET was as accurate as the MSEL-A in assessing VR and RL, yet
      took a 44% less time. Results suggested that the MSEL-A and the MSEL-ET could be
      viable measures for accurately assessing developmental domains in children with
      RTT.

PMID- 29194025
TI  - Self-Advocacy Services for People With Intellectual and Developmental
      Disabilities: A National Analysis.
AB  - Self-advocacy plays an important role in facilitating the empowerment of people
      with intellectual and developmental disabilities (IDD), and helps people with IDD
      develop the skills necessary for the participant direction of services. The
      purpose of this study was to examine Medicaid Home and Community Based Services
      (HCBS) 1915(c) waivers across the nation to determine how states were utilizing
      self-advocacy services for people with IDD. Findings revealed approximately half
      of waivers provided self-advocacy services; however, less than .01% of waiver
      spending was projected for stand-alone self-advocacy services. States need to
      expand the provision of self-advocacy services for people with IDD in order to
      strengthen their ability to direct their waiver services and exercise their
      rights.

PMID- 29194027
TI  - Resumenes al Espanol.

PMID- 29194026
TI  - Linking Staff Burnout to Family Members' Satisfaction in Centers for People With
      Intellectual Disabilities: A Service Chain Approach.
AB  - Research in centers for people with intellectual and developmental disabilities
      has somewhat neglected the relationship between workers' burnout and users'
      service evaluations. Two independent survey studies tested this connection. In
      the first study (100 centers, 714 workers, and 612 family members), results
      confirmed that burnout has a negative relationship with workers' perceptions of
      service quality. In turn, these perceptions are associated with the service
      quality perceptions of family members and their satisfaction with the service. In
      a replication sample (86 centers, 601 workers, and 819 family members), we
      reproduced these results and added situational constraints in the model. Both
      social and technical constraints correlated positively and significantly with
      burnout. These studies offer a view of the relationships between burnout and
      service quality.

PMID- 29194028
TI  - Presidential Address: Promoting Health and Wellness.

PMID- 29194029
TI  - Development of the Supported Decision Making Inventory System.
AB  - Supported decision making has received increased attention as an alternative to
      guardianship and a means to enable people with intellectual and developmental
      disabilities to exercise their right to legal capacity. Assessments are needed
      that can used by people with disabilities and their systems of supports to
      identify and plan for needed supports to enable decision making. This article
      describes the steps taken to develop such an assessment tool, the Supported
      Decision Making Inventory System (SDMIS), and initial feedback received from self
      advocates with intellectual disability. The three sections of the SDMIS
      (Supported Decision Making Personal Factors Inventory, Supported Decision Making
      Environmental Demands Inventory, and Decision Making Autonomy Inventory) are
      described and implications for future research, policy, and practice are
      discussed.

PMID- 29194031
TI  - Lies, damned lies, and statistics.

PMID- 29194030
TI  - Prevalence of Dysphagia in People With Intellectual Disability: A Systematic
      Review.
AB  - Dysphagia (feeding and swallowing disorder) is associated with serious health
      complications and psychosocial sequelae. This review summarizes international
      research relating to the prevalence of dysphagia in people with intellectual
      disability. Studies published from 1990 to July 2016 were identified using
      Medline, Cinahl, PsycINFO, Web of Science, email requests, and cross-citations.
      Twenty studies were identified. Dysphagia in people with intellectual disability
      appears to be associated with more severe levels of intellectual disability,
      comorbid cerebral palsy, and motor impairments. However, further research with
      representative samples of people with intellectual disability using adequate
      methods of assessment are required in order to provide more precise prevalence
      estimates and clarify factors that may be associated with dysphagia in this
      population.

PMID- 29194032
TI  - Phlebotomus (Paraphlebotomus) chabaudi and Phlebotomus riouxi: closely related
      species or synonyms?
AB  - Phlebotomus riouxi Depaquit, Killick-Kendrick & Leger 1998 was described as a
      species closely related to Phlebotomus chabaudi Croset, Abonnenc & Rioux 1970,
      differing mainly by the size and number of setae of the coxite basal lobe.
      Molecular studies carried out on several populations from Algeria and Tunisia and
      based on mitochondrial genes cytochrome b (Cytb) and cytochrome oxidase I (COI)
      supported the typological validity of these two species. Recently, specimens from
      a single population in southern Tunisia were morphologically identified as Ph.
      riouxi, Ph. chabaudi and intermediates, but were clustered in the same clade
      according to their Cytb and nuclear gene elongation factor-1 alpha (EF-1alpha)
      sequences. These species were thus synonymized. To further explore this synonymy,
      we carried out a molecular study on specimens from Algeria and Tunisia using the
      same molecular markers and a part of 28S rDNA. We did not find any
      morphologically intermediate specimens in our sampling. We highlighted
      differences between the genetic divergence rates within and between the two
      species for the three markers and we identified new haplotypes. The sequence
      analysis did not reveal any signature of introgression in allopatric nor in
      sympatric populations such as in the Ghomrassen population. Phylogenetic analyses
      based on our specimens revealed that the two main clades are Ph. chabaudi and Ph.
      riouxi, in agreement with the morphological identification. These results support
      the validity of Ph. riouxi and Ph. chabaudi as typological species.

PMID- 29194033
TI  - Immunoproteomic analysis of the protein repertoire of unsporulated Eimeria
      tenella oocysts.
AB  - The apicomplexan protozoans Eimeria spp. cause coccidioses, the most common
      intestinal diseases in chickens. Coccidiosis is associated with significant
      animal welfare issues and has a high economic impact on the poultry industry.
      Lack of a full understanding of immunogenic molecules and their precise functions
      involved in the Eimeria life cycles may limit development of effective vaccines
      and drug therapies. In this study, immunoproteomic approaches were used to define
      the antigenic protein repertoire from the total proteins of unsporulated Eimeria
      tenella oocysts. Approximately 101 protein spots were recognized in sera from
      chickens infected experimentally with E. tenella. Forty-six spots of unsporulated
      oocysts were excised from preparative gels and identified by matrix-assisted
      laser desorption ionization time-of-flight MS (MALDI-TOF-MS) and MALDI-TOF/TOF
      MS. For unsporulated oocysts, 13 known proteins of E. tenella and 17 homologous
      proteins to other apicomplexan or protozoan parasites were identified using the
      'Mascot' server. The remaining proteins were searched against the E. tenella
      protein sequence database using the 'Mascot in-house' search engine (version 2.1)
      in automated mode, and 12 unknown proteins were identified. The amino acid
      sequences of the unknown proteins were searched using BLAST against non-redundant
      sequence databases (NCBI), and 9 homologous proteins in unsporulated oocyst were
      found homologous to proteins of other apicomplexan parasites. These findings may
      provide useful evidence for understanding parasite biology, pathogenesis,
      immunogenicity and immune evasion mechanisms of E. tenella.

PMID- 29194034
TI  - Redescription of Cichlidogyrus philander (Monogenea, Ancyrocephalidae) using
      scanning electron microscopy (SEM) and molecular analysis.
AB  - The sclerotized structures of monogeneans have traditionally been studied by
      light microscopy and different staining techniques. Recently, enzymatic digestion
      followed by scanning electron microscopy (SEM) has enabled the examination of
      structural details not visible with light microscopy. In order to obtain better,
      and more accurate, morphological information on sclerotized structures not
      affected by mounting medium or cover slip pressure, the sclerites of
      Cichlidogyrus philander Douellou, 1993 (Monogenea, Ancyrocephalidae), collected
      from Pseudocrenilabrus philander (Weber, 1897), were redescribed using SEM.
      Parasites were collected from Padda Dam, Gauteng, South Africa and soft tissue
      was digested to release the sclerotized structures. The digested tissue also
      provided sufficient genetic material for molecular characterization of this
      species. Cichlidogyrus philander is characterised by a penis with a sharp,
      curved, lateral termination, an accessory piece with a hook-like extremity that
      may appear forked terminally, and lack of a visible vagina. The transverse bars
      have concave and convex surfaces with ribs on the concave surface. The dorsal bar
      bears fenestrations at the base of the auricles and the ventral and dorsal gripi
      are dissimilar. Furthermore, the large first pair of uncinuli shows lateral wings
      on the left side of the base. On top of this wing, a ball-like structure with a
      small fenestration is visible. Genetic characters derived from the 28S rDNA, the
      COI mitochondrial DNA and ITS1 rDNA regions distinguish C. philander from all
      other Cichlidogyrus sequenced species.

PMID- 29194035
TI  - The long non-coding RNA CRNDE promotes cervical cancer cell growth and
      metastasis.
AB  - This study was intended to analyze effects of lncRNA CRNDE on cervical cancer
      cell growth and metastasis. Fifty pairs of cervical cancer tissues and
      corresponding adjacent tissues were collected. Expressions of long non-coding
      RNAs (lncRNAs) in tissue samples were detected by microarray analysis. Expression
      levels of CRNDE in cervical cancer cells and normal cells were detected by qRT
      PCR. Cell-counting kit-8 (CCK-8) assay and clone formation assay were utilized to
      evaluate cell growth. Wound healing assay and Transwell assay were conducted to
      detect the migratory and invasive capability of cervical cancer cells. The
      expressions of CRNDE in cervical cancer tissues and cells were higher than those
      in normal tissues and cells. CCK-8 assay and clone formation assay showed that
      the knockdown of CRNDE could inhibit the cell proliferation of HeLa and C-33A
      cells. Wound healing assay indicated that the downregulation of CRNDE expression
      could suppress the cell migration. The result of a Transwell assay demonstrated
      that the number of invasion cells reduced in the CRNDE-si group in comparison
      with the Mock group. LncRNA CRNDE could promote the cell growth and stimulate the
      metastasis of cervical cancer cells.

PMID- 29194036
TI  - Prognostic and predictive value of EGFR and EGFR-ligands in blood of breast
      cancer patients: a systematic review.
AB  - Epidermal growth factor receptor (EGFR) serves as a co-target for dual/pan-EGFR
      inhibitors in breast cancer. Findings suggest that EGFR and EGFR-ligands are
      involved in resistance towards certain breast cancer treatments. The aim is to
      explore the validity of EGFR and EGFR-ligands in blood as prognostic and
      predictive biomarkers in breast cancer. The systematic review was conducted in
      accordance to the PRISMA guidelines. Literature searches were conducted to
      identify publications exploring correlations between EGFR/EGFR-ligands in
      serum/plasma of breast cancer patients and prognostic/predictive outcome
      measures. Sixteen publications were eligible for inclusion. Twelve studies
      evaluated EGFR, whereas five studies evaluated one or more of the EGFR-ligands.
      Current evidence indicates associations between low baseline serum-EGFR and
      shorter survival or reduced response to treatment in patients with advanced
      breast cancer, especially in patients with estrogen and/or progesterone receptor
      positive tumors. The prognostic and predictive value of EGFR and EGFR-ligands in
      blood has only been investigated in highly selected subsets of breast cancer
      patients and most studies were small. This is the first systematic review
      evaluating the utility of EGFR and EGFR-ligands as predictive and prognostic
      biomarkers in blood in breast cancer. Further exploration in large well-designed
      studies is needed.

PMID- 29194037
TI  - Serum prolactin levels across pregnancy and the establishment of reference
      intervals.
AB  - BACKGROUND: Reference intervals (RIs) play key roles in clinical diagnosis,
      treatment and prognosis. However, RIs for clinical testing tend to be confined to
      the general population, and RIs for pregnant women are not very comprehensive. In
      this study, we establish RIs for prolactin (PRL) in healthy pregnant and
      postpartum women in the Chinese population. METHODS: Healthy pregnant women
      (n=378) were divided into groups according to whether they were in the first,
      second or third trimester of pregnancy. Healthy postpartum women (n=493) were
      separated into four groups according to mode of delivery as follows: postvaginal
      (24 and 48 h) or postcesarean (24 and 48 h). Healthy, non-pregnant women (n=123)
      were enrolled as a control group. Serum PRL levels were measured by
      electrochemiluminescence immunoassay, and RIs were established for each group.
      RESULTS: The RIs for PRL were as follows: healthy non-pregnant women, 178.89
      757.52 MUIU/mL; first trimester, 621.20-3584.00 MUIU/mL; second trimester,
      1432.00-5349.68 MUIU/mL; third trimester, 4087.33-9733.65 MUIU/mL; 24 and 48 h
      postvaginal delivery (combined), 7865.36-10998.86 MUIU/mL; and 24 and 48 h
      postcesarean delivery, 4556.41-7675.99 and 6578.45-9980.45 MUIU/mL, respectively.
      CONCLUSIONS: PRL RIs for pregnant women were established according to trimester,
      days postpartum and mode of delivery, thus providing a clinical reference for
      medical staff.

PMID- 29194038
TI  - Commutability of control materials for external quality assessment of serum
      apolipoprotein A-I measurement.
AB  - BACKGROUND: The aim of the current study was to evaluate the commutability of
      commercial control materials and human serum pools and to investigate the
      suitability of the materials for the external quality assessment (EQA) of serum
      apolipoprotein A-I (apo A-I) measurement. METHODS: The Clinical and Laboratory
      Standards Institute (CLSI) EP14-A3 protocol was used for the commutability study.
      Apo A-I concentrations in two levels of commercial control materials used in EQA
      program, two fresh-frozen human serum pools (FSPs) and two frozen human serum
      pools prepared from residual clinical specimens (RSPs) were measured along with
      50 individual samples using nine commercial assays. Measurement results of the 50
      individual samples obtained with different assays were pairwise analyzed by
      Deming regression, and 95% prediction intervals (PIs) were calculated. The
      commutability of the processed materials was evaluated by comparing the
      measurement results of the materials with the limits of the PIs. RESULTS: The FSP
      1 was commutable for all the 36 assay pairs, and FSP-2 was commutable for 30
      pairs; RSP-1 and RSP-2 showed commutability for 27/36 and 22/36 assay pairs,
      respectively, whereas the two EQA materials were commutable only for 4/36 and
      5/36 assay pairs, respectively. CONCLUSIONS: Non-commutability of the tested EQA
      materials has been observed among current apo A-I assays. EQA programs need
      either to take into account the commutability-related biases in the
      interpretation of the EQA results or to use more commutable materials. Frozen
      human serum pools were commutable for most of the assays.

PMID- 29194039
TI  - Validation of a high-performance liquid chromatography method for thiopurine S
      methyltransferase activity in whole blood using 6-mercaptopurine as substrate.
AB  - BACKGROUND: Variation in metabolism, toxicity and therapeutic efficacy of
      thiopurine drugs is largely influenced by genetic polymorphisms in the thiopurine
      S-methyltransferase (TPMT) gene. Determination of TPMT activity is routinely
      performed in patients to adjust drug therapy. METHODS: We further optimized a
      previously established high-performance liquid chromatography (HPLC) method by
      measuring TPMT activity in whole blood instead of isolated erythrocytes, which is
      based on conversion of 6-mercaptopurine to 6-methylmercaptopurine using S
      adenosyl-methionine as methyl donor. RESULTS: The simplified TPMT whole-blood
      method showed similar or better analytical and diagnostic performance compared
      with the former erythrocyte assay. The whole-blood method was linear for TPMT
      activities between 0 and 40 nmol/(mL.h) with a quantification limit of 0.1
      nmol/(mL.h). Within-day imprecision and between-day imprecision were <=5.1% and
      <=8.5%, respectively. The optimized method determining TPMT activity in whole
      blood (y) showed agreement with the former method determining TPMT activity in
      erythrocytes (x) (n=45, y=1.218+0.882x; p>0.05). Phenotype-genotype concordance
      (n=300) of the whole-blood method was better when TPMT activity was expressed per
      volume of whole blood (specificity 92.2%), whereas correction for hematocrit
      resulted in lower genotype concordance (specificity 86.9%). A new cutoff for the
      whole-blood method to distinguish normal from reduced TPMT activity was
      determined at <=6.7 nmol/(mL.h). CONCLUSIONS: This optimized TPMT phenotyping
      assay from whole blood using 6-MP as substrate is suitable for research and
      routine clinical analysis.

PMID- 29194040
TI  - Effect of preanalytical and analytical variables on the clinical utility of mean
      platelet volume.
AB  - BACKGROUND: The study endpoint was to analyze the effect of preanalytical (time,
      temperature, anticoagulant) and analytical (imprecision, correlation between
      volume and platelet concentration) variables on mean platelet volume (MPV). A
      further aim was to calculate in an adult population the reference intervals using
      the Sysmex XE-5000 analyzer. A critical evaluation was also made of the clinical
      utility of these parameters. METHODS: Analyses of the above values were performed
      in duplicate in 170 healthy adults of both sexes: (1) within 30 min from
      collection, and (2) after 4 h. To evaluate stability over time, the value of the
      platelet parameters of 20 subjects were determined, a re-analysis being performed
      for a period of up to 24 h on samples maintained at room temperature and 4
      degrees C using either K2-EDTA or Na-citrate as anticoagulants. RESULTS: The
      stability over time of MPV closely depends on the anticoagulant used, storage
      temperature and time interval between venipuncture and analysis. An inverse, non
      linear correlation between MPV and platelet count was also found. CONCLUSIONS: In
      view of their effect on MPV and other related indices, the preanalytical and
      analytical variables make them, little more than experimental.

PMID- 29194041
TI  - Rare inclusion bodies within monocytes at accelerated phase of Chediak-Higashi
      syndrome.

PMID- 29194044
TI  - Spondyloepiphyseal or spondylometaphyseal dysplasia in ancient Greek art.

PMID- 29194043
TI  - The role of corticosteroid-binding globulin in the evaluation of adrenal
      insufficiency.
AB  - Cortisol is a hydrophobic molecule that is largely bound to corticosteroid
      binding globulin (CBG) in the circulation. In the assessment of adrenal
      insufficiency, many clinicians measure a total serum cortisol level, which
      assumes that CBG is present in normal concentrations and with a normal binding
      affinity for cortisol. CBG concentration and affinity are affected by a number of
      common factors including oral contraceptive pills (OCPs), fever and infection, as
      well as rare mutations in the serine protease inhibitor A6 (SERPINA6) gene, and
      as such, total cortisol levels might not be the ideal way to assess adrenal
      function in all clinical circumstances. This paper reviews the limitations of
      immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the
      measurement of total cortisol, the challenges of measuring free serum cortisol
      directly as well as the difficulties in calculating an estimated free cortisol
      from total cortisol, CBG and albumin concentrations. Newer approaches to the
      evaluation of adrenal insufficiency, including the measurement of cortisol and
      cortisone in the saliva, are discussed and a possible future role for these tests
      is proposed.

PMID- 29194042
TI  - A case of Riley Ruvalcaba syndrome with a novel PTEN mutation accompanied by
      diffuse testicular microlithiasis and precocious puberty.
AB  - BACKGROUND: Bannayan Riley Ruvalcaba syndrome (BRRS) is exceedingly rare, with
      only about 50 reported cases to date. CASE PRESENTATION: We report a patient with
      hypoglycemia, precocious puberty and diffuse testicular microlithiasis
      accompanying BRRS, and think that this case is important in the light of a newly
      identified mutation in the PTEN gene. CONCLUSIONS: Close attention must be paid
      in terms of PTEN mutations in cases of macrocephaly and accompanying neurological
      and dermatological findings.

PMID- 29194045
TI  - Mothering under the influence: how perinatal drugs of abuse alter the mother
      infant interaction.
AB  - Although drug-abusing women try to moderate their drug and alcohol use during
      pregnancy, they often relapse at a time when childcare needs are high and
      maternal bonding is critical to an infant's development. In the clinical setting,
      the search for the neural basis of drug-induced caregiving deficits is complex
      due to several intervening variables. Rather, the preclinical studies that
      control for drug dose and regimen, as well as for gestational and postpartum
      environment, allow a precise determination of the effects of drugs on maternal
      behaviour. Given the relevance of the issue, this review will gather reports on
      the phenotypic correlates of maternal behaviour in preclinical studies, and focus
      on the detrimental consequences on the mother-infant interaction exerted by the
      perinatal use of alcohol, nicotine, cannabis, cocaine and stimulants and opiates.
      The drug-induced disruptions of this maternal repertoire are associated with
      adverse maternal and infant outcomes. A comprehensive overview will help promote
      the refinement of the treatment approaches toward maternal drug use disorders and
      maternal misbehaviour, in favour of augmented parenting resiliency.

PMID- 29194046
TI  - Updates on the biology of serotonin and tryptophan hydroxylase.
AB  - PURPOSE OF REVIEW: To summarize the most recent findings relevant to the biology
      of serotonin (5-hydroxytryptamine; 5-HT) and the enzyme tryptophan hydroxylase
      (TPH) in human gastrointestinal disease. RECENT FINDINGS: Serotonin is
      synthesized in the central nervous system (CNS) and the gastrointestinal tract
      where it is secreted from enteroendocrine cells. Its biosynthesis is regulated by
      two isoforms of the enzyme TPH of which TPH1 is localized predominantly in
      gastrointestinal enteroendocrine cells. Serotonin activates the peristaltic
      reflexes, regulates gastrointestinal motility, and has a role in intestinal
      inflammation. Inhibition of TPH with novel molecules represents a new
      pharmacological tool in the successful management of carcinoid syndrome in
      patients with gastrointestinal neuroendocrine tumors (GI-NETs). Certain 5-HT
      receptor subtype agonists and antagonists are useful in the treatment of
      functional gastrointestinal disorders. SUMMARY: The gastrointestinal tract is the
      largest storage organ for serotonin where its biosynthesis is regulated by TPH1.
      It has several important functions in gastrointestinal motility, secretion, and
      inflammation. Furthermore, TPH represents a target for inhibitory pharmacological
      therapy of serotonin access states such as the carcinoid syndrome.

PMID- 29194047
TI  - Editorial overview: gastrointestinal regulatory peptides.

PMID- 29194048
TI  - New Swallowing Method to Improve Pharyngeal Passage of a Bolus by Creating
      Negative Pressure in the Esophagus-Vacuum Swallowing.
AB  - Herein, we present a case of a patient with Wallenberg syndrome with severe
      bulbar dysphagia who discovered a unique swallowing method: creating strong
      negative pressure in the esophagus to improve pharyngeal passage of a bolus. A 47
      yr-old man presented with a subarachnoid hemorrhage secondary to a ruptured
      aneurysm in the right vertebral artery. After coil embolization, he experienced
      severe dysphagia due to Wallenberg syndrome and required tube feeding. Eighty-one
      days after the onset of the stroke, a videofluoroscopic swallowing evaluation
      revealed that the bolus was rapidly sucked into the esophagus. High-resolution
      manometry showed weak constriction of the pharynx simultaneous with forced,
      voluntary constriction of the diaphragm before swallowing; this created negative
      pressure in the esophagus. The authors named this unique swallowing method
      "vacuum swallowing." Ultimately, the patient was able to eat an ordinary diet via
      the use of this technique. Vacuum swallowing is a unique method of improving
      pharyngeal passage of a bolus by creating strong negative pressure in the
      esophagus. Additional studies are necessary to determine whether vacuum
      swallowing can be successfully used for other forms of dysphagia.

PMID- 29194049
TI  - Preserving the Shoulder Function of an Elite Para Triathlete: A Case Report.
AB  - Shoulder pain in wheelchair users that participate in competitive adaptive sports
      can be a troublesome condition. Shoulder pain not only affects athletic
      performance, but also functional activities such as wheelchair propulsion and
      weight bearing during transfers. Managing pain in these athletes thus presents a
      unique challenge due to the difficulty in achieving relative rest and the need to
      modify athletic shoulder-focused rehabilitation strategies. In all athletes, it
      is vital to establish an early, accurate diagnosis and optimize conservative
      treatment prior to considering surgical interventions in order to avoid excessive
      shoulder-related morbidity, loss of function, and worse - loss of independence.

PMID- 29194050
TI  - Update on the management of acute heart failure.
AB  - PURPOSE OF REVIEW: We provide a concise review of recent studies focusing on the
      management of patients with acute heart failure (AHF). RECENT FINDINGS: In well
      designed randomized trials, no mortality benefit has been observed with the use
      of diuretics, ultrafiltration, inotropes and vasodilators in AHF. Recent trials
      examining the role of novel inotropes and vasodilators as well as the role of
      mineralocorticoid receptor antagonists in the AHF population, is reviewed.
      SUMMARY: The focus of therapy in AHF should be directed towards symptom
      management. No mortality benefit has been observed despite good quality studies.

PMID- 29194051
TI  - Blood, tissue and imaging biomarkers in calcific aortic valve stenosis: past,
      present and future.
AB  - PURPOSE OF REVIEW: Calcific aortic valve stenosis is the most prevalent valvular
      heart disease in the high-income countries. To this date, no medical therapy has
      been proven to prevent or to stop the progression of aortic valve stenosis. The
      physiopathology of aortic valve stenosis is highly complex and involves several
      signalling pathways, as well as genetic related factors, which delay the
      elaboration of effective pharmacotherapies. Moreover, it is difficult to predict
      accurately the progression of the valve stenosis and finding the optimal timing
      for aortic valve replacement remains challenging. Therefore, the present review
      makes an inventory of the most recent and promising circulating and imaging
      biomarkers related to the underlying mechanisms involved in the physiopathology
      of aortic valve stenosis, as well as the biomarkers associated with the left
      ventricular (LV) remodelling and subsequent dysfunction in patients with aortic
      valve stenosis. RECENT FINDINGS: Over the last decade, several blood, tissue and
      imaging biomarkers have been investigated in aortic valve stenosis patients. At
      the aortic valve level, these biomarkers are mostly associated and/or involved
      with processes such as lipid infiltration and oxidation, chronic inflammation and
      fibrocalcific remodelling of the valve. Moreover, recent findings suggest that
      aging and sex hormones might interact with these multiple processes. Several
      studies demonstrated the usefulness of circulating biomarkers such as
      lipoprotein(a), brain natriuretic peptides and high-sensitivity cardiac troponin,
      which are very close to clinical routine. Furthermore, noninvasive imaging
      biomarkers including positron emission tomography and cardiac magnetic resonance,
      which provide a detailed view of the disease activity within the aortic valve and
      its repercussion on the left ventricle, may help to improve the understanding of
      aortic valve stenosis physiopathology and enhance the risk stratification. Other
      biomarkers such as von Willebrand factor and microRNAs are promising but further
      studies are needed to prove their additive value in aortic valve stenosis.
      SUMMARY: Most of the biomarkers are used in research and thus, are still being
      investigated. However, some biomarkers including plasma level of lipoprotein(a),
      F-sodium fluoride, brain natriuretic peptides and high-sensitivity cardiac
      troponin can be or are very close to be used for the clinical management of
      patients with aortic valve stenosis. Moreover, a multibiomarker approach might
      provide a more global view of the disease activity and improve the management
      strategies of these patients.

PMID- 29194052
TI  - Machine learning in heart failure: ready for prime time.
AB  - PURPOSE OF REVIEW: The aim of this review is to present an up-to-date overview of
      the application of machine learning methods in heart failure including diagnosis,
      classification, readmissions and medication adherence. RECENT FINDINGS: Recent
      studies have shown that the application of machine learning techniques may have
      the potential to improve heart failure outcomes and management, including cost
      savings by improving existing diagnostic and treatment support systems. Recently
      developed deep learning methods are expected to yield even better performance
      than traditional machine learning techniques in performing complex tasks by
      learning the intricate patterns hidden in big medical data. SUMMARY: The review
      summarizes the recent developments in the application of machine and deep
      learning methods in heart failure management.

PMID- 29194053
TI  - Cervical Injuries in Drowning Cases: A Case Report and a Review of Literature.
AB  - Discovery of bruises in the muscles of the neck and a fracture of the hyoid bone
      in a body recovered from water makes the diagnosis and the determination of the
      manner of death difficult.The aims of this work are to report a case of a drowned
      body with cervical injuries and to highlight the importance of interpreting these
      findings accurately.A 39-year-old woman was found dead face down in a 6-m deep
      well with a 3-m water level. She was mentally disturbed and had a history of
      suicide attempts. In fact, she had previously attempted to jump into that well in
      an attempt to put an end to her life. The autopsy revealed bruises in the muscles
      of the neck and a bruise associated with a fracture of the left horn of the hyoid
      bone.The mechanism for the origin of drowning-related neck injuries will be
      discussed.

PMID- 29194054
TI  - A Rare Vehicle-Assisted Ligature Hanging: Suicide at the Wheel.
AB  - Suicide by hanging inside a motor vehicle is a rare occurrence. A 48-year-old
      woman suffering from major depression was found having agonal breathing inside
      her automobile. A 20-mm diameter blue nylon rope was wrapped tightly around her
      neck, with its other end tied to a nearby wooden fence post. Despite
      resuscitation attempts, she was declared deceased after several minutes. The
      vehicle was located in an area with a slight downward slope. The motor was off.
      It was in neutral gear, with the parking brake disengaged. Consequently, the
      gravitational forces, attributable to the mass of the vehicle and the declivity
      of the terrain, caused the rope to tighten.The dynamics fulfill the criteria for
      a partial hanging, given the difference in height between the point at which the
      rope was secured to the post and woman's neck, which in turn presented the
      typical oblique upward groove.This case, thus, represents a unique mode of
      partial hanging inside a passenger vehicle, rarely reported in the literature.
      The relative lack of internal injury is also noteworthy, along with the fact that
      the victim was discovered while still alive. The latter feature can be explained
      by the absence of the sudden or violent acceleration forces that can be generated
      with the engine on.

PMID- 29194055
TI  - Hinged Lids and Fatal Head Entrapment in Early Childhood.
AB  - Young children are at risk of head entrapment because they often do not
      understand potentially dangerous situations or have the intellectual or physical
      capabilities to self-extricate. Two cases of head entrapment due to hinged lids
      are presented to demonstrate another rare lethal situation specific to the very
      young. Case 1 was a 14-month-old boy found suspended by his neck in a
      semikneeling position under a toilet seat. A horizontal linear bruise measuring
      0.6 * 20 mm was present on the right side of the neck with petechial hemorrhages
      of the forehead. Death was due to neck compression from head entrapment with
      aspiration of gastric contents. Case 2 was a 17-month-old girl found suspended by
      her neck from the side of her crib by a hinged cover. A horizontal linear bruise
      measuring 10 * 50 mm was present immediately below the suprasternal notch with
      numerous petechial hemorrhages of the conjunctivae and face. Death was due to
      neck compression from head entrapment. Although these cases are very rare, they
      do show the potential danger that hinged lids may present to toddlers. Autopsy
      evaluations require comparisons of injuries with the structure and edges of the
      entrapping device/object.

PMID- 29194056
TI  - Neonatal Nurses Experience Unintended Consequences and Risks to Patient Safety
      With Electronic Health Records.
AB  - In this article, we examine the unintended consequences of nurses' use of
      electronic health records. We define these as unforeseen events, change in
      workflow, or an unanticipated result of implementation and use of electronic
      health records. Unintended consequences experienced by nurses while using
      electronic health records have been well researched. However, few studies have
      focused on neonatal nurses, and it is unclear to what extent unintended
      consequences threaten patient safety. A new instrument called the Carrington
      Gephart Unintended Consequences of Electronic Health Record Questionnaire has
      been validated, and secondary analysis using the tool explored the phenomena
      among neonatal nurses (N = 40). The purposes of this study were to describe
      unintended consequences of use of electronic health records for neonatal nurses
      and to explore relationships between the phenomena and characteristics of the
      nurse and the electronic health record. The most frequent unintended consequences
      of electronic health record use were due to interruptions, followed by a heavier
      workload due to the electronic health record, changes to the workflow, and
      altered communication patterns. Neonatal nurses used workarounds most often with
      motivation to better assist patients. Teamwork was moderately related to higher
      unintended consequences including patient safety risks (r = 0.427, P = .007),
      system design (r = 0.419, P = .009), and technology barriers (r = 0.431, P =
      .007). Communication about patients was reduced when patient safety risks were
      high (r = -0.437, P = .003). By determining the frequency with which neonatal
      nurses experience unintended consequences of electronic health record use, future
      research can be targeted to improve electronic health record design through
      customization, integration, and refinement to support patient safety and better
      outcomes.

PMID- 29194057
TI  - Approaches and techniques to avoid development or progression of acute
      respiratory distress syndrome.
AB  - PURPOSE OF REVIEW: Despite major improvement in ventilation strategies, hospital
      mortality and morbidity of the acute respiratory distress syndrome (ARDS) remain
      high. A lot of therapies have been shown to be ineffective for established ARDS.
      There is a growing interest in strategies aiming at avoiding development and
      progression of ARDS. RECENT FINDINGS: Recent advances in this field have explored
      identification of patients at high-risk, nonspecific measures to limit the risks
      of inflammation, infection and fluid overload, prevention strategies of
      ventilator-induced lung injury and patient self-inflicted lung injury, and
      pharmacological treatments. SUMMARY: There is potential for improvement in the
      management of patients admitted to intensive care unit to reduce ARDS incidence.
      Apart from nonspecific measures, prevention of ventilator-induced lung injury and
      patient self-inflicted lung injury are of major importance.

PMID- 29194058
TI  - Gait Deviations Associated With Concussion: A Systematic Review.
AB  - BACKGROUND: Gait deviations resulting from concussion are important to consider
      in the diagnosis, treatment progression, and return to activity after a
      concussion. OBJECTIVE: To identify quantifiable gait deviations associated with
      concussion across populations and time since injury. METHODS AND MATERIALS: Six
      electronic databases were systematically searched from January 1974 to September
      2016. Studies selected included original data, had an analytic design, and
      reported a quantifiable gait parameter in individuals who had sustained a
      concussion as defined by the American Congress of Rehabilitation Medicine or
      related definitions. Preferred Reporting Items for Systematic reviews and Meta
      Analysis guidelines were followed. Two independent authors assessed study quality
      [Downs and Black (DB) criteria] and level of evidence (Oxford Center of Evidence
      Based Medicine Model). RESULTS: Of 2650 potentially relevant articles, 21 level 4
      studies were included. The median DB score was 12/33 (range 10-16). Heterogeneity
      in gait parameters and timing of postconcussion testing precluded meta-analysis.
      There is consistent level 4 evidence of increased medial-lateral center-of-mass
      displacement, and inconsistent level 4 evidence of decreased gait velocity after
      concussion. Further, there is preliminary level 4 evidence that gait deficits may
      exist beyond the typical 10-day recovery period and return to activity.
      CONCLUSION: These findings suggest that individuals who have suffered a
      concussion may sway more in the frontal plane, and walk slower compared to
      healthy controls. Consensus about the most important gait parameters for
      concussion diagnosis and clinical management are lacking. Further, high-quality
      prospective cohort studies evaluating changes in gait from time of concussion to
      return to activity, sport, recreation and/or work are needed.

PMID- 29194059
TI  - Self-Reported Mild Traumatic Brain Injuries in Relation to Rumination and
      Depressive Symptoms: Moderating Role of Sex Differences and a Brain-Derived
      Neurotrophic Factor Gene Polymorphism.
AB  - OBJECTIVE: Mild traumatic brain injuries (mTBIs) have frequently been associated
      with the emergence and persistence of depressive symptoms. However, the factors
      which contribute to the increased risk for depression after these head injuries
      remain unclear. Accordingly, we examined the relationship between frequency of
      self-reported mTBIs and current symptoms of depression and the mediating role of
      rumination and cognitive flexibility. We also examined whether these relations
      were moderated by sex differences and the presence of the Val66Met polymorphism
      in a gene coding for brain-derived neurotrophic factor (BDNF). DESIGN:
      Retrospective, cross-sectional. SETTING: Carleton University. PARTICIPANTS: Two
      hundred nineteen Carleton University undergraduate students. MAIN OUTCOME
      MEASURES: Cognitive flexibility as assessed by the Wisconsin Card Sorting Task
      (WCST); subtypes of rumination (Ruminative Response Scale; Treynor, Gonzalez, and
      Nolen-Hoeksema, 2003); depressive symptoms (Beck Depression Inventory; Beck,
      Ward, and Mendelson, 1961). RESULTS: Greater frequency of self-reported mTBIs was
      associated with more frequent depressive rumination among women, but not men,
      which was accompanied by elevated current depressive symptoms. In addition, among
      Met allele carriers of the BDNF polymorphism, but not those who were Val
      homozygotes, greater frequency of mTBIs was related to higher levels of brooding,
      which was accompanied by heightened depressive symptoms. Brain-derived
      neurotrophic factor genotype also moderated the relationship between self
      reported mTBIs and cognitive flexibility in that more frequent mTBIs were
      associated with more perseverative errors on the WCST among Met carriers, but not
      Val homozygotes. CONCLUSIONS: The present findings raise the possibility that the
      evolution of depression after mTBIs may be dependant on a BDNF polymorphism and
      sex differences.

PMID- 29194060
TI  - Cervical Deformity and Potential Difficult Airway Management in Klippel-Feil
      Syndrome.

PMID- 29194061
TI  - Reporting of Observational Research in ANESTHESIOLOGY: The Importance of Data
      Quality: Trust but Verify.

PMID- 29194065
TI  - Delayed Respiratory Depression Secondary to Opioid Overdose After Multimodal
      Analgesia With Transversus Abdominis Plane Blocks in Postanesthesia Care Unit: A
      Case Report.
AB  - Pain control after open abdominal surgery often includes multimodal analgesia
      with thoracic epidural or transversus abdominis plane (TAP) block. After
      liposomal bupivacaine was approved for TAP blocks in 2015, it became an
      alternative to indwelling catheters. However, the pharmacokinetics and safety of
      its use during the perioperative period have not been thoroughly investigated,
      especially in conjunction with parenteral opioids. We present a case report of an
      elderly patient having urgent laparoscopic converted to open abdominal surgery,
      who experienced postoperative respiratory depression in the recovery room after
      multimodal therapy with liposomal bupivacaine TAP blocks, intravenous (IV)
      opioids, and ketorolac.

PMID- 29194062
TI  - Cost-effectiveness Analysis of Intraoperative Cell Salvage for Obstetric
      Hemorrhage.
AB  - BACKGROUND: Cost-effectiveness analyses on cell salvage for cesarean delivery to
      inform national and societal guidelines on obstetric blood management are
      lacking. This study examined the cost-effectiveness of cell salvage strategies in
      obstetric hemorrhage from a societal perspective. METHODS: Markov decision
      analysis modeling compared the cost-effectiveness of three strategies: use of
      cell salvage for every cesarean delivery, cell salvage use for high-risk cases,
      and no cell salvage. A societal perspective and lifetime horizon was assumed for
      the base case of a 26-yr-old primiparous woman presenting for cesarean delivery.
      Each strategy integrated probabilities of hemorrhage, hysterectomy, transfusion
      reactions, emergency procedures, and cell salvage utilization; utilities for
      quality of life; and costs at the societal level. One-way and Monte Carlo
      probabilistic sensitivity analyses were performed. A threshold of $100,000 per
      quality-adjusted life-year gained was used as a cost-effectiveness criterion.
      RESULTS: Cell salvage use for cases at high risk for hemorrhage was cost
      effective (incremental cost-effectiveness ratio, $34,881 per quality-adjusted
      life-year gained). Routine cell salvage use for all cesarean deliveries was not
      cost-effective, costing $415,488 per quality-adjusted life-year gained. Results
      were not sensitive to individual variation of other model parameters. The
      probabilistic sensitivity analysis showed that at the $100,000 per quality
      adjusted life-year gained threshold, there is more than 85% likelihood that cell
      salvage use for cases at high risk for hemorrhage is favorable. CONCLUSIONS: The
      use of cell salvage for cases at high risk for obstetric hemorrhage is
      economically reasonable; routine cell salvage use for all cesarean deliveries is
      not. These findings can inform the development of public policies such as
      guidelines on management of obstetric hemorrhage.

PMID- 29194066
TI  - Exercise as an Intervention to Mitigate Decreased Cognitive Function From Cancer
      and Cancer Treatment: An Integrative Review.
AB  - BACKGROUND: Decreased cognitive function associated with non-central nervous
      system cancers and cancer treatment significantly affects cancer survivors'
      quality of life. Exercise may be an effective intervention to mitigate decreased
      cognitive function. OBJECTIVE: The aim of this article is to conduct an
      integrative review to summarize and critique the available evidence related to
      the use of exercise as a potential intervention for decreased cognitive function
      from cancer and cancer treatment. METHODS: We conducted an integrative review
      through January 2016 utilizing PubMed, CINAHL, and PsycINFO. Broad inclusion
      criteria included any quantitative study in which cognitive outcomes were
      reported in relationship to any type of exercise for adult cancer survivors.
      Effect sizes were calculated when possible based on available data. RESULTS:
      Twenty-six studies were included for review. The majority of studies (including
      aerobic or resistance exercise as well as mindfulness-based exercise) were
      associated with some improved cognitive outcomes. However, studies varied
      significantly in levels of evidence, cognitive domains assessed, and types of
      cognitive measures. Less than half of the studies included objective measures of
      cognitive function. CONCLUSIONS: The evidence shows promising trends for the use
      of exercise as a potential intervention for improving cognitive function
      following cancer and cancer treatment, but questions remain concerning exercise
      type, timing of initiation, intensity, frequency, and duration. IMPLICATIONS FOR
      PRACTICE: Additional research is warranted to understand how various types of
      exercise influence cognitive function in the cancer survivor population and to
      better understand the mechanisms driving these effects. Trial designs that
      include both objective and subjective measures of cognitive function are needed.

PMID- 29194068
TI  - Polycythemia vera and essential thrombocythemia: algorithmic approach.
AB  - PURPOSE OF REVIEW: To describe an algorithm-based approach, whenever available,
      to the diagnosis, the risk stratification criteria informing therapy and the
      current management of polycythemia vera and essential thrombocythemia. RECENT
      FINDINGS: Description of recurrent genetic abnormalities in driver genes,
      including Janus Kinase 2 (JAK2), myeloproliferative leukemia and calreticulin, a
      better appreciation of the key diagnostic role of bone marrow features, results
      of large epidemiologic studies and a few but landmark controlled clinical trials
      produced in the last decade, all resulted in a reappraisal of the approach to
      polycythemia vera and essential thrombocythemia. SUMMARY: The revised 2017 WHO
      classification of polycythemia vera and essential thrombocythemia allows early
      diagnosis and accurate distinction from other chronic myeloproliferative
      neoplasms, particulary prefibrotic myelofibrosis. The prognostic value of
      selected mutations is being appreciated and JAK2V617F mutation is currently
      incorporated as risk variable in prognostic system for essential thrombocythemia.
      Risk-adjusted stratification is used to select therapeutic approaches that
      include target agents. However, there is not yet a curative approach to these
      hematologic neoplasms, and although their management has much improved in the
      last decades, the associated morbidity and mortality remains significant and may
      be worsened by toxicities of therapeutic agents. Therefore, several clinically
      relevant endpoints remain unmet.

PMID- 29194067
TI  - Personalized therapy in a GRIN1 mutated girl with intellectual disability and
      epilepsy.

PMID- 29194069
TI  - Changing patterns in treatment of angle closure glaucoma.
AB  - PURPOSE OF REVIEW: Angle closure glaucoma is a leading cause of blindness
      globally and trends of how best to treat this disease are evolving. The advent of
      anterior segment imaging aids our understanding of pathogenesis and allows more
      robust and objective measurement of treatment modalities. We will also review
      recent literature regarding the role of laser and surgical interventions for the
      treatment of primary angle closure disease. RECENT FINDINGS: Recent studies
      evaluating the efficacy of laser peripheral iridotomy (LPI) in primary angle
      closure suspects (PACs) show that while it is a safe intervention and initially
      anterior chamber angle widens following the laser treatment, the effect is lost
      with time. Only a small minority of PACs patients develop primary angle closure
      (PAC) or primary angle closure glaucoma (PACG). Trials evaluating argon laser
      peripheral iridoplasty (ALPI) have failed to show a substantial clinical benefit.
      In patients with early or moderate PACG and those with PAC with IOP over 30 mmHg,
      clear lens extraction is associated with better clinical and quality of life
      outcomes than LPI. SUMMARY: Recent evidence supports initial clear lens
      extraction in the context of PACG or primary angle closure with IOP more than 30
      mmHg.

PMID- 29194070
TI  - Changes in gut microbiota during development of compulsive checking and locomotor
      sensitization induced by chronic treatment with the dopamine agonist quinpirole.
AB  - Long-term treatment of rats with the D2/D3 dopamine agonist quinpirole induces
      compulsive checking (proposed as animal model of obsessive-compulsive disorder)
      and locomotor sensitization. The mechanisms by which long-term use of quinpirole
      produces those behavioral transformations are not known. Here we examined whether
      changes in gut microbiota play a role in these behavioral phenomena, by
      monitoring the development of compulsive checking and locomotor sensitization at
      the same time as measuring the response of gut microbiota to chronic quinpirole
      injections. Two groups of rats received nine injections of saline (n=16) or
      quinpirole (n=15; 0.25 mg/kg), at weekly intervals for the first 5 weeks and then
      two injections per week until the end of treatment. After each injection, rats
      were placed on a large open field for 55 min, and their behavior was video
      recorded for subsequent analysis. Fecal matter was collected after each trial and
      frozen for bacterial community profiling of the 16S rRNA gene, using paired-end
      reads of the V3 region. The results indicated that the induction of locomotor
      sensitization and compulsive checking was accompanied by changes in several
      communities of bacteria belonging to the order Clostridiales (class Clostridia,
      phylum Firmicutes), and predominantly in Lachnospiraceae and Ruminococcaceae
      families of bacteria. It is suggested that changes in these microbes may serve to
      support the energy use requirements of compulsive checking and obsessive
      compulsive disorder.

PMID- 29194071
TI  - Revisiting the phenotypic and genetic profiling of anergic T cells mediating long
      term transplant tolerance.
AB  - PURPOSE OF REVIEW: Herein our focus will be to revisit peripheral tolerance
      mechanisms and in particular 'active' or 'dominant' tolerance as originally
      defined and mediated by regulatory CD4FoxP3 T lymphocytes (Treg) and also T-cell
      anergy that appears as a major mainstay to support long-term allograft survival.
      RECENT FINDINGS: It is at the same time interesting and rewarding that the tool
      that recently guided our efforts along this path is the in-vivo use of CD3
      antibody, the first monoclonal introduced in the clinic (Orthoclone OKT3) about
      35 years ago to treat and prevent rejection of renal allografts. Beyond their
      immunosuppressive activity, whenever administered judiciously, CD3 antibodies
      promote robust allograft tolerance through selective purging of alloreactive
      effectors, resetting Treg-mediated active tolerance and promoting a unique subset
      of anergic CD8 T cells. SUMMARY: The new findings discussed open up new
      perspectives from both a fundamental and a clinical point of view. In basic
      research, concrete molecular signaling paths are now spotted to finely dissect
      the conditions that lead to the establishment and maintenance of robust T
      lymphocyte anergy mediating allograft tolerance. In the clinic, this may rapidly
      translate into novel biomarkers to be used in parallel to the ones already
      available, to better adapt posttransplant immunotherapy and monitor for long-term
      allograft acceptance.

PMID- 29194072
TI  - Prenatal thrombosis of renal veins and the inferior vena cava in a newborn with
      double heterozygosity for the factor V Leiden and prothrombin gene G20210A
      mutations: a case report.
AB  - : Renal vein thrombosis in a neonate is a rare but well recognized condition with
      low mortality but high morbidity. The cause has not been explained clearly yet
      but is probably a multifactorial process that includes inherited prothrombotic
      abnormalities. Antenatal onset of renal vein thrombosis is important due to the
      increased risk for permanent organ damage. We report a case of prenatal
      thrombosis of the renal veins and the inferior vena cava in a newborn with double
      heterozygosity for factor V Leiden and prothrombin gene mutations who had
      persistently impaired renal function requiring chronic peritoneal dialysis.

PMID- 29194073
TI  - Update on trends in childhood tuberculosis.
AB  - PURPOSE OF REVIEW: Although tuberculosis (TB) causes much morbidity and mortality
      in children, diagnosis and treatment remain challenging. Recently, children have
      gained increasing attention in research and clinical trials driving improved
      contact management, case identification and treatment of both drug-susceptible
      and drug-resistant TB. This review highlights some recent advances. RECENT
      FINDINGS: The tuberculin skin test is the most widely used test to distinguish
      Mycobacterium tuberculosis (M. tuberculosis) infection from active TB, however,
      using M. tuberculosis-specific, antigenic stimulation of CD4 and CD8 cells appear
      more effective. The use of Xpert MTB/RIF to identify M. tuberculosis in clinical
      samples, together with novel sampling methods have in part, overcome the
      difficulty of sampling and increased case identification capacity. Advances in
      treating both drug-susceptible and drug-resistant childhood TB show promise in
      being more paediatric friendly and improving adherence. Dosing strategies for
      drug-sensitive TB have improved with dispersible fixed drug combinations now
      available. In the treatment and prevention of drug-resistant TB, however,
      research involving the use of newer and more effective drugs currently
      recommended for adults, are still ongoing in children. SUMMARY: The World Health
      Organization aims to end the TB epidemic by 2035 whereas the United Nations'
      Sustainable Developmental Goals sets this ambitious target for 2030. Therefore,
      adequate funding and implementing effective national TB programs must be
      prioritized, particularly in high-burden, low-income settings.

PMID- 29194074
TI  - Developmental dysplasia of the hip: an update on diagnosis and management from
      birth to 6 months.
AB  - PURPOSE OF REVIEW: Our understanding of the epidemiology, diagnosis, and
      management of developmental dysplasia of the hip (DDH) is evolving. This review
      focuses on the most up-to-date literature on DDH in patients from birth to six
      months of age. RECENT FINDINGS: Well known risk factors for DDH include family
      history, female sex, and breech positioning. Recent evidence suggests higher
      birth weight is a risk, whereas prematurity may be protective. Screening includes
      physical examination of all infant hips and imaging when abnormal findings or
      risk factors are present. Treatment in the first six months consists of a
      harness, with 70-95% success. Failure risk factors include femoral nerve palsy,
      static bracing, irreducible hips, initiation after seven weeks of age, right hip
      dislocation, Graf-IV hips, and male sex. Rigid bracing may be trialed if
      reduction with a harness fails and closed reduction is indicated after failed
      bracing. If the hip is still irreducible, nonconcentric, or unstable, open
      reduction may be required following closed reduction. Evidence does not support
      delaying hip reduction until the ossific nucleus is present. SUMMARY: DDH affects
      1-7% of infants. All infants should be examined and selective screening with
      imaging should be performed for abnormal physical exams or risk factors. Early
      treatment is associated with optimal outcomes.

PMID- 29194075
TI  - Cutaneous angiosarcoma: update on biology and latest treatment.
AB  - PURPOSE OF REVIEW: The present review aims to provide readers with the latest
      updates on the biology and clinical management of cutaneous angiosarcoma (cAS).
      RECENT FINDINGS: The genomic alteration of cAS is heterogeneous. Mutations are
      enriched in the mitosis-activated kinase (MAPK) pathway. Functional analysis has
      identified molecules that may serve as potential markers and therapeutic targets
      of angiosarcoma. These molecules include survivin, HSP90, FOXM1, miR-497-5p,
      KCa3.1, and miR210.This body of knowledge has not yet transferred to clinical
      practice. The mainstay of treatment for cAS remains surgery followed by
      postoperative radiotherapy. The efficacy of paclitaxel as an adjuvant
      chemotherapy is suggested.For patients with advanced cAS, paclitaxel is the
      treatment of choice. There are also second-line treatment options that are
      supported by evidence of varying strength. A multikinase inhibitor, pazopanib,
      has been assessed in several studies, most of which support its efficacy for
      angiosarcoma. Bevacizumab monotherapy may be effective for angiosarcoma. The
      efficacy of eribulin mesylate and trabectedin for angiosarcoma is currently being
      assessed. Recent publications highlighted the role of the immune system in the
      biology of cAS. SUMMARY: Future research efforts should focus on the following
      aspects of cAS: drug development directed at recent molecular targets, clinical
      trials designed specifically for patients with cAS, and the role of immunotherapy
      for cAS.

PMID- 29194076
TI  - Morcellation equipment: past, present, and future.
AB  - PURPOSE OF REVIEW: This review was written in an effort to describe the evolution
      of power morcellation equipment from their creation to their current state. In
      addition, this review addresses the continuously evolving equipment involved with
      power morcellation and looks to describe where the field is headed in the future.
      In addition, recent professional and federal recommendations have changed the way
      power morcellation is being approached and has led to the development of
      contained morcellation systems, which, although in their infancy, are also being
      proven to be well tolerated options. RECENT FINDINGS: This article will review
      the most current research on electronic power morcellation and the multiple
      attempts to prove superiority from the many different types of equipment, and
      also the many different approaches to morcellation. In addition, with the
      adaptation to contained morcellation, this review will cover research focused on
      optimizing a containment system and the techniques involved. SUMMARY: In summary,
      this review is aimed at describing many of the currently available power
      morcellation products and contained morcellation systems in an effort to allow
      physicians to understand the different options available, and to discuss well
      tolerated, effective, and clinically proven techniques that can lead to improved
      surgical outcomes in the future.

PMID- 29194077
TI  - Advances in targeting HER2-positive breast cancer.
AB  - PURPOSE OF REVIEW: Breast cancer is the most common malignancy in women and HER2
      positive disease comprises about 15% of all breast cancer cases. Over the last
      few years, substantial advances have been made in treatment of early breast
      cancer (EBC) and advanced (ABC) HER2-positive (HER2+) breast cancer. The present
      review summarizes the major publications on HER2+ breast cancer in the year 2017
      and discusses their clinical relevance. RECENT FINDINGS: The clinically most
      relevant data in 2017 relates to the EBC setting. The St. Gallen Consensus 2017
      for the first time recommended neoadjuvant treatment as standard of care in HER2+
      EBC. Moreover, the APHINITY trial demonstrated efficacy of adjuvant dual antibody
      based HER2 blockade. Data in MBC mostly confirmed established treatment
      strategies. SUMMARY: Clinical data presented in 2017 for HER2+ breast cancer
      confirmed current guidelines and extended treatment options for patients. First
      intriguing steps were made towards de-escalation in the EBC setting.

PMID- 29194079
TI  - Compliance With Best Practice Guidelines for Neurodevelopmental Supportive Care
      in South Africa: A Situational Analysis.
AB  - Neurodevelopmental supportive care provides preterm infants with evidence-based
      care to ensure the best possible neurological outcomes. The study aimed to
      determine the compliance of current nursing care practices with best practice
      guidelines by means of a situational analysis. The situational analysis was done
      in 2 cycles in the neonatal intensive care units (n = 25) of a private healthcare
      provider in South Africa. Structured observations were done in cycle 1 using the
      Implementation of Neurodevelopmental Supportive Care checklist. Cycle 2 comprised
      focus group discussions to verify findings from cycle 1. Seventeen conclusion
      statements were formulated, which were thematically combined to be presented as 9
      categories: neonatal intensive care unit design, individualized care, family
      centered care, infant positioning, handling techniques, environmental
      manipulation, pain management, knowledge of infant behavior, and feeding. The
      conclusion statements identified improvement opportunities in current practice
      and offer suggestions, which can be used to guide an implementation strategy for
      best practice guidelines of neurodevelopmental supportive care in the neonatal
      intensive care units of the private healthcare group in future. Addressing
      improvement opportunities in all the categories will ensure that all aspects of
      the guideline requirements are met, resulting in a comprehensive strategy
      improving practice and patient outcomes.

PMID- 29194078
TI  - Stress From the Neonatal Intensive Care Unit to Home: Paternal and Maternal
      Cortisol Rhythms in Parents of Premature Infants.
AB  - To examine cortisol diurnal rhythms over the transition from the critical care
      setting to home for fathers and mothers of very low-birth-weight infants,
      including how cortisol is associated with psychosocial stress and parenting sense
      of competence. This cohort study in a level III neonatal intensive care unit and
      the general community had 86 parents complete salivary collection and self
      reported psychosocial measures. Salivary samples were collected 3 times a day on
      the day before discharge, and on 3 subsequent days at home. Self-report measures
      included the Perceived Stress Scale and the Parenting Sense of Competence Scale,
      which measure parenting satisfaction. Fathers showed increased physiologic stress
      over the transition home, reflected by flattening of slopes, lower wakeup, and
      higher bedtime cortisol. Mothers reporting increases in perceived stress over the
      transition home had higher bedtime cortisol, suggesting a link between higher
      perceived stress and higher physiologic stress. Results were significant after
      controlling for breastfeeding, insurance status, and gestational age. This study
      examined a physiologic marker of stress in parents with very low-birth-weight
      infants, finding sex disparities in diurnal cortisol patterns during the
      transition from neonatal intensive care unit to the community. Fathers may be
      especially susceptible to stressors during this transition.

PMID- 29194080
TI  - Temporal Fine Structure Processing, Pitch, and Speech Perception in Adult
      Cochlear Implant Recipients.
AB  - OBJECTIVES: The aim of the study was to investigate the link between temporal
      fine structure (TFS) processing, pitch, and speech perception performance in
      adult cochlear implant (CI) recipients, including bimodal listeners who may
      benefit better low-frequency (LF) temporal coding in the contralateral ear.
      DESIGN: The study participants were 43 adult CI recipients (23 unilateral, 6
      bilateral, and 14 bimodal listeners). Two new LF pitch perception tests-harmonic
      intonation (HI) and disharmonic intonation (DI)-were used to evaluate TFS
      sensitivity. HI and DI were designed to estimate a difference limen for
      discrimination of tone changes based on harmonic or inharmonic pitch glides.
      Speech perception was assessed using the newly developed Italian Sentence Test
      with Adaptive Randomized Roving level (STARR) test where sentences relevant to
      everyday contexts were presented at low, medium, and high levels in a fluctuating
      background noise to estimate a speech reception threshold (SRT). RESULTS:
      Although TFS and STARR performances in the majority of CI recipients were much
      poorer than those of hearing people reported in the literature, a considerable
      intersubject variability was observed. For CI listeners, median just noticeable
      differences were 27.0 and 147.0 Hz for HI and DI, respectively. HI outcomes were
      significantly better than those for DI. Median STARR score was 14.8 dB. Better
      performers with speech reception thresholds less than 20 dB had a median score of
      8.6 dB. A significant effect of age was observed for both HI/DI tests, suggesting
      that TFS sensitivity tended to worsen with increasing age. CI pure-tone
      thresholds and duration of profound deafness were significantly correlated with
      STARR performance. Bimodal users showed significantly better TFS and STARR
      performance for bimodal listening than for their CI-only condition. Median
      bimodal gains were 33.0 Hz for the HI test and 95.0 Hz for the DI test. DI
      outcomes in bimodal users revealed a significant correlation with unaided hearing
      thresholds for octave frequencies lower than 1000 Hz. Median STARR scores were
      17.3 versus 8.1 dB for CI only and bimodal listening, respectively. STARR
      performance was significantly correlated with HI findings for CI listeners and
      with those of DI for bimodal listeners. CONCLUSIONS: LF pitch perception was
      found to be abnormal in the majority of adult CI recipients, confirming poor TFS
      processing of CIs. Similarly, the STARR findings reflected a common performance
      deterioration with the HI/DI tests, suggesting the cause probably being a lack of
      access to TFS information. Contralateral hearing aid users obtained a remarkable
      bimodal benefit for all tests. Such results highlighted the importance of TFS
      cues for challenging speech perception and the relevance to everyday listening
      conditions. HI/DI and STARR tests show promise for gaining insights into how TFS
      and speech perception are being limited and may guide the customization of CI
      program parameters and support the fine tuning of bimodal listening.

PMID- 29194081
TI  - Urine RNA Processing in a Clinical Setting: Comparison of 3 Protocols.
AB  - OBJECTIVE: The objective of this study was to compare quantitative and
      qualitative RNA extraction results from clinical voided urine samples between 3
      commercially available extraction protocols. METHODS: For phase 1, fresh voided
      urine samples from 10 female subjects were collected and processed in clinic and
      transported to the laboratory with cold packs. RNA was purified with 1 of 3 RNA
      extraction protocols: (1) TRI Reagent Protocol; (2) Absolutely RNA Nanoprep Kit;
      and (3) ZR Urine RNA Isolation Kit. Real-time polymerase chain reactions (RT-PCR)
      were performed. As the ZR Urine RNA Isolation Kit provided the highest quality
      RNA in phase 1, for phase 2, RNA was extracted from 9 additional voided urine
      specimens using this kit to perform additional qualitative analyses. RESULTS:
      Median RNA yield was significantly higher with the TRI Reagent Protocol as
      compared with the other protocols (P = 0.007). However, there was a significantly
      lower median threshold cycle value from polymerase chain reaction (indicating
      improved downstream application performance) with the ZR Urine RNA Isolation Kit
      as compared with the other methods (P = 0.005). In phase 2, the median RNA
      integrity number of urine RNA was 2.5 (range, 1.6-5.9). CONCLUSIONS: Although
      other methods may provide a higher quantity of RNA, when using clinical urine
      samples, the ZR Urine RNA Isolation Kit provided the highest quality of extracted
      RNA. This kit is especially attractive for the clinical setting because it does
      not require an initial centrifugation step. The urine RNA obtained with this kit
      may be useful for polymerase chain reaction but is not likely to be of high
      enough integrity for RNA sequencing.

PMID- 29194082
TI  - From Open to MIS: Robotic Surgery Enables Surgeons to Do More With Less.

PMID- 29194083
TI  - Management of Reducible Ventral Hernias: Clinical Outcomes and Cost-effectiveness
      of Repair at Diagnosis Versus Watchful Waiting.
AB  - OBJECTIVE: To compare long-term clinical and economic outcomes associated with 3
      management strategies for reducible ventral hernia: repair at diagnosis (open or
      laparoscopic) and watchful waiting. BACKGROUND: There is variability in ventral
      hernia management. Recent data suggest watchful waiting is safe; however, long
      term clinical and economic outcomes for different management strategies remain
      unknown. METHODS: We built a state-transition microsimulation model to forecast
      outcomes for individuals with reducible ventral hernia, simulating a cohort of 1
      million individuals for each strategy. We derived cohort characteristics (mean
      age 58 years, 63% female), hospital costs, and perioperative mortality from the
      Nationwide Inpatient Sample (2003-2011), and additional probabilities, costs, and
      utilities from the literature. Outcomes included prevalence of any repair,
      emergent repair, and recurrence; lifetime costs; quality-adjusted life years
      (QALYs); and incremental cost-effectiveness ratios. We performed stochastic and
      probabilistic sensitivity analyses to identify parameter thresholds that affect
      optimal management, using a willingness-to-pay threshold of $50,000/QALY.
      RESULTS: With watchful waiting, 39% ultimately required repair (14% emergent) and
      24% recurred. Seventy per cent recurred with repair at diagnosis. Laparoscopic
      repair at diagnosis was cost-effective compared with open repair at diagnosis
      (incremental cost-effectiveness ratio $27,700/QALY). The choice of operative
      strategy (open vs laparoscopic) was sensitive to cost and postoperative quality
      of life. When perioperative mortality exceeded 5.2% or yearly recurrence exceeded
      19.2%, watchful waiting became preferred. CONCLUSIONS: Ventral hernia repair at
      diagnosis is very cost-effective. The choice between open and laparoscopic repair
      depends on surgical costs and postoperative quality of life. In patients with
      high risk of perioperative mortality or recurrence, watchful waiting is
      preferred.

PMID- 29194084
TI  - GRIT and Resilience: Keys to the Development of the Halsted Resident in the John
      Cameron Era.

PMID- 29194085
TI  - Breath Volatile Organic Compound Profiling of Colorectal Cancer Using Selected
      Ion Flow-Tube Mass Spectrometry.
AB  - OBJECTIVE: BACKGROUND:: Breath VOCs have the potential to noninvasively diagnose
      cancer. METHODS: Exhaled breath samples were collected using 2-L double-layered
      Nalophan bags, and were analyzed using selected-ion-flow-tube mass-spectrometry.
      Gold-standard test for comparison was endoscopy for luminal inspection and
      computed tomography (CT) to confirm cancer recurrence. Three studies were
      conducted: RESULTS:: CONCLUSION:: This study suggests the association of a single
      breath biomarker with the primary presence and recurrence of CRCa. Further
      multicenter validation studies are required to validate these findings.

PMID- 29194086
TI  - Roux-en-Y Gastric Bypass: Ten-year Results in a Cohort of 658 Patients.
AB  - OBJECTIVE: The aim of this paper is to report, with a high follow-up rate, 10
      year results in a large cohort of patients after Roux-en-Y gastric bypass (RYGBP)
      done essentially by laparoscopy. BACKGROUND: RYGBP has been performed for 50
      years, including 20 years by laparoscopy, yet very few long-term results have
      been reported, mostly after open surgery. METHODS: Prospective bariatric database
      established since the introduction of bariatric surgery. Retrospective data
      analysis on weight loss, long-term complications, quality of life, and
      comorbidities. RESULTS: In all, 658 consecutive patients (515 women/143 men) were
      included: 554 with primary RYGBP, 104 with reoperative RYGBP. There was 1 (0.15%)
      postoperative death. Thirty-two (5%) patients died during follow-up from causes
      unrelated to surgery. Ten years after primary RYGBP, patients lost 28.6 +/- 10.5%
      of their initial weight, corresponding to a mean of 13.2 body mass index (BMI)
      units. Among them, 72.8% achieved a BMI <35. Weight loss >=20% was seen in 80.3%
      and <10% in 3.9% of patients. Results were similar in patients undergoing primary
      or reoperative RYGBP, but were better in patients who were initially less obese
      (BMI <50 kg/m) than in superobese patients. Quality of life and comorbidities
      significantly improved with 80% resolution or improvement of metabolic
      comorbidities. All patients required supplementations, and 14.6% required long
      term reoperation. CONCLUSIONS: RYGBP provides long-term satisfactory weight loss
      up to 10 years, and significantly improves quality of life and comorbidities.
      Long-term complications requiring reoperation can develop. Mineral and vitamin
      supplementation are universally necessary. Other more effective surgical options
      should be discussed in patients with very severe obesity.

PMID- 29194087
TI  - Combining the Old With the New: The Next Journey of the Clinical Risk Score.

PMID- 29194088
TI  - The Range and Impact of Postmigration Stressors During Treatment of Trauma
      Affected Refugees.
AB  - Trauma-affected refugees commonly experience postmigration stressors, which can
      compound conflict-related emotional distress. Our study aimed to assess clinician
      rated frequency and types of postmigration stressors deemed to be interfering
      with the treatment of refugees attending a service for trauma-related mental
      distress. A total of 116 patients completed 6 months of multidisciplinary
      treatment. Clinician-rated postmigration stressors were registered at each
      session. Outcome measures were Harvard Trauma Questionnaire and Global Assessment
      of Functioning, function (GAF-F) and symptom. Postmigration stressors were deemed
      to impact on 39.1% of treatment sessions with medical personnel. Issues related
      to work, finances, and family were the most frequently identified stressors.
      Postmigration stressors interfering with treatment were more common among male
      refugees, those living alone, those from Middle Eastern origin, and persons with
      low baseline GAF-F. Explicitly identifying and, where possible, dealing with
      postmigration stressors may assist in averting their interference with the
      treatment of distress in refugees.

PMID- 29194089
TI  - Quetiapine Dose Adjustments in Pregnant and Postpartum Women With Bipolar
      Disorder.

PMID- 29194091
TI  - Menthol reduces phototoxicity pain in a mouse model of photodynamic therapy.
AB  - Phototoxicity-induced pain is a major clinical problem triggered by light acting
      on photosensitising drugs or endogenous porphyrins, notably protoporphyrin IX
      (PpIX), an intermediary in heme biosynthesis. Protoporphyrin IX accumulates in
      individuals with erythropoietic protoporphyria and is elevated during
      photodynamic therapy subsequent to application of 5-aminolevulinic acid (ALA).
      Pain occurs during irradiation of PpIX and responds poorly to conventional
      analgesics. Our objective was to develop a model of PpIX phototoxicity pain and
      investigate the potential of menthol as an analgesic. Application of ALA to the
      tails of C57 black and SWISS white mice caused PpIX accumulation and nociception
      during irradiation (630 nm at 3.7 J/cm). Despite similar PpIX accumulation, C57
      mice exhibited less pain behavior compared with SWISS mice because of light
      absorption by pigmentation. Irradiation of ALA-treated dorsal root ganglion
      neurons caused phototoxicity-evoked action potentials (APs) in both mouse
      strains. The antioxidant L-tryptophan increased the light dose required to elicit
      such APs. By contrast, the addition of keratinocytes to neuronal cultures
      decreased the threshold for APs, suggesting a requirement for proliferating
      cells. Inhibition of fatty acid amide hydrolase, selective antagonism of TRPV1 or
      the application of lidocaine or its quaternary derivative QX-314, reduced AP
      frequency, whereas antagonism of TRPA1 had no effect. These results suggest that
      products of singlet oxygen-mediated lipid peroxidation trigger nociceptor
      activation via TRPV1. Menthol inhibited phototoxicity-evoked APs and reduced pain
      behavior when applied topically to mice. These findings suggest that menthol
      might provide pain relief in patients experiencing PpIX-phototoxicity pain caused
      by photodynamic therapy or erythropoietic protoporphyria.

PMID- 29194090
TI  - The association between uric acid levels and different clinical manifestations of
      coronary artery disease.
AB  - AIMS: Uric acid (UA) has been associated with the presence and severity of
      coronary artery disease. To further assess the role of UA role in coronary artery
      disease, we investigated UA levels in both healthy asymptomatic middle-aged
      individuals and in different subgroups of hospitalized patients with suspected or
      definite myocardial infarction (MI). PATIENTS AND METHODS: The severity of
      coronary artery calcification (CAC) was examined in asymptomatic individuals
      (n=1039) using a noncontrast computed tomography scan. Hospitalized patients with
      suspected acute MI (n=772) were grouped according to troponin I (TnI)
      concentrations: (i) elevated TnI concentrations (>0.03 ug/l) with subdivision
      according to the type of MI and other clinical conditions associated with
      myocardial injury, or (ii) nonelevated TnI concentrations (<=0.03 ug/l). RESULTS:
      UA was not associated with the severity of CAC in asymptomatic individuals when
      adjusting for relevant risk factors. Patients with type 2 MI and patients with
      myocardial injury associated with conditions of myocardial ischemia showed
      significantly higher UA levels (0.390 mmol/l, P=0.002 and 0.400 mmol/l, P=0.001,
      respectively) than patients with type 1 MI (0.329 mmol/l), after adjusting for
      other risk factors. CONCLUSION: UA was not correlated with the severity of CAC in
      asymptomatic middle-aged individuals, and patients with type 2 MI or ischemic
      myocardial injury were shown to have higher UA levels than type 1 MI patients.
      This observation is concordant with the hypothesis that UA might be involved in
      the pathophysiological mechanisms leading to an imbalance in the oxygen
      supply/demand ratio in type 2 MI and ischemic myocardial injury.

PMID- 29194092
TI  - Clinicopathologic Features and Prognostic Impact of Lymph Node Involvement in
      Patients With Breast Implant-associated Anaplastic Large Cell Lymphoma.
AB  - Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T
      cell lymphoma that arises around breast implants. Most patients manifest with
      periprosthetic effusion, whereas a subset of patients develops a tumor mass or
      lymph node involvement (LNI). The aim of this study is to describe the pathologic
      features of lymph nodes from patients with BI-ALCL and assess the prognostic
      impact of LNI. Clinical findings and histopathologic features of lymph nodes were
      assessed in 70 patients with BI-ALCL. LNI was defined by the histologic
      demonstration of ALCL in lymph nodes. Fourteen (20%) patients with BI-ALCL had
      LNI, all lymph nodes involved were regional, the most frequent were axillary
      (93%). The pattern of involvement was sinusoidal in 13 (92.9%) cases, often
      associated with perifollicular, interfollicular, and diffuse patterns. Two cases
      had Hodgkin-like patterns. The 5-year overall survival was 75% for patients with
      LNI and 97.9% for patients without LNI at presentation (P=0.003). Six of 49
      (12.2%) of patients with tumor confined by the capsule had LNI, compared with LNI
      in 8/21 (38%) patients with tumor beyond the capsule. Most patients with LNI
      achieved complete remission after various therapeutic approaches. Two of 14
      (14.3%) patients with LNI died of disease compared with 0/56 (0%) patients
      without LNI. Twenty percent of patients with BI-ALCL had LNI by lymphoma, most
      often in a sinusoidal pattern. We conclude that BI-ALCL beyond capsule is
      associated with a higher risk of LNI. Involvement of lymph nodes was associated
      with decreased overall survival. Misdiagnosis as Hodgkin lymphoma is a pitfall.

PMID- 29194094
TI  - The Squamoid Cells in Biphasic Squamoid Alveolar Renal Carcinoma Present
      Cytophagocytosis (Not Emperipolesis) of Apoptotic Neutrophilic Granulocytes.

PMID- 29194093
TI  - CDKN2A/B Deletion and Double-hit Mutations of the MAPK Pathway Underlie the
      Aggressive Behavior of Langerhans Cell Tumors.
AB  - Langerhans cell histiocytosis (LCH) has a mostly favorable outcome, whereas
      Langerhans cell sarcoma (LCS) is an aggressive tumor. It is still unclear whether
      any specific molecular alterations could underlie the aggressive behavior of
      Langerhans cell proliferations. We used targeted next-generation sequencing and
      array-comparative genomic hybridization to profile 22 LCH samples from different
      patients together with 3 LCS samples corresponding to different relapses from the
      same patient. The third LCS relapse was a composite tumor including both B-cell
      chronic lymphocytic leukemia and LCS components. The 22 LCH samples were mostly
      of bone origin and showed classic histophenotypical features. Array-comparative
      genomic hybridization showed in all 3 LCS samples a similar homozygous somatic
      loss affecting the CDKN2A/B locus, whereas the 17 informative LCH samples did not
      show any detectable abnormality. In the 3 LCS samples, targeted next-generation
      sequencing of 495 cancer genes detected common mutations in KMT2D/MLL2 and in
      both MAP2K1 and NRAS genes, whereas BRAF was not mutated. A NOTCH1 mutation was
      acquired in 2 LCS samples. The composite LCS/B-cell chronic lymphocytic leukemia
      tumor showed the same genetic profile in its 2 components. LCH samples showed
      mutually exclusive mutations of BRAF (8/20) and MAP2K1 (4/19), but no mutation of
      KMT2D, NRAS nor NOTCH1. These results suggest that CDKN2A/B deletion and/or
      simultaneous mutations of MAP2K1 and NRAS may underlie the aggressive behavior of
      Langerhans cell tumors, and thus could be useful for the diagnosis of malignancy
      in histiocytic neoplasms. The MAPK pathway "double hit" profile provides a basis
      for targeted therapy in LCS patients.

PMID- 29194095
TI  - Is nonmetastatic cutaneous melanoma predictable through genomic biomarkers?
AB  - Cutaneous melanoma is a highly aggressive skin cancer whose treatment and
      prognosis are critically affected by the presence of metastasis. In this study,
      we address the following issue: which gene transcripts and what kind of
      interactions between them can allow to predict nonmetastatic from metastatic
      melanomas with a high level of accuracy? We carry out a meta-analysis on the
      first gene expression set of the Leeds melanoma cohort, as made available online
      on 11 May 2016 through the ArrayExpress platform with MicroArray Gene Expression
      number 4725. According to the authors, primary melanoma mRNA expression was
      measured in 204 tumours using an illumina DASL HT12 4 whole-genome array. The
      tumour transcripts were selected through a recently proposed predictive-based
      regression algorithm for gene-network selection. A set of 64 equivalent models,
      each including only two gene transcripts, were each sufficient to accurately
      classify primary tumours into metastatic and nonmetastatic melanomas. The
      sensitivity and specificity of the genomic-based models were, respectively, 4%
      (95% confidence interval: 0.11-21.95%) and 99% (95% confidence interval: 96.96
      99.99%). The very high specificity coupled with a significantly large positive
      likelihood ratio leads to a conclusive increase in the likelihood of disease when
      these biomarkers are present in the primary tumour. In conjunction with other
      highly sensitive methods, this approach can aspire to be part of the future
      standard diagnosis methods for the screening of metastatic cutaneous melanoma.
      The small dimension of the selected transcripts models enables easy handling of
      large-scale genomic testing procedures. Moreover, some of the selected
      transcripts have an understandable link with what is known about cutaneous
      melanoma oncogenesis, opening a window on the molecular pathways underlying the
      metastatic process of this disease.

PMID- 29194097
TI  - An Autologous Leukocyte-Reduced Platelet-Rich Plasma Therapy for Chronic Injury
      of the Medial Collateral Ligament in the Knee: A Report of 3 Successful Cases.
AB  - Some patients complain of chronic persistent medial knee pain after isolated low
      grade injuries of medial collateral ligaments (MCL). These injuries often respond
      to various conservative treatments but insufficient healing of ligaments is
      believed to be responsible for symptoms in this group of patients. We report on
      successful treatment of chronically symptomatic MCL injuries in 3 patients using
      autologous leukocyte-reduced platelet-rich plasma (PRP) injections. There were 3
      men with a mean age of 39.3 years and a mean disease duration of 10 months.
      Magnetic resonance imaging showed discontinuities of superficial layers and
      thickness of deep layers in the proximal MCL. After PRP injections, all cases
      returned to their sport activities at a previous level as without symptoms, and
      complete healing of proximal ligaments was identified on magnetic resonance
      images. The outcomes indicated that PRP injections led to successful repair for
      chronic injuries of MCL in knees.

PMID- 29194096
TI  - The Interplay between Genes and Psychosocial Home Environment on Physical
      Activity.
AB  - INTRODUCTION: Genetic factors contribute to individual differences in physical
      activity, but it remains uncertain whether the magnitude of the genetic effects
      is modified by variations in home environments. We aimed to examine to what
      extent the psychosocial home environment in childhood and adolescence modifies
      the genetic influences on leisure time physical activity in young adulthood.
      METHODS: Participants were Finnish twins (N = 3305) who reported their leisure
      time physical activity at age 24 yr. The psychosocial home environment was
      assessed by twins at ages 12, 14, and 17 yr, as well as by their parents when the
      twins were age 12 yr. Gene-environment interaction modeling was performed with
      OpenMx software. RESULTS: Parental ratings of positive home atmosphere as well as
      the twins' ratings of both positive home atmosphere at age 14 yr and lower
      relational tensions at ages 12 and 14 yr predicted higher leisure time physical
      activity levels in young adulthood (regression coefficients = 0.33-0.64).
      Parental perceptions as well as the twins' perceptions of positive home
      atmosphere at ages 14 and 17 yr increased the additive genetic variation
      (moderation effects: 0.55, 95% confidence interval [CI] = 0.29-0.80; 0.60, 95% CI
      = 0.26-1.05; and 0.52, 95% CI = 0.19-0.87, respectively). The twins' ratings of
      positive home atmosphere at age 12 yr and lower relational tensions at ages 12
      and 14 yr increased the unique environmental variation of their subsequent
      physical activity (moderation effects: 0.46, 95% CI = 0.19-0.60; 0.48, 95% CI =
      0.29-0.64; and 0.85, 95% CI = 0.12-0.95, respectively). CONCLUSIONS: A
      psychosocial home environment that is warm and supportive in childhood and
      adolescence not only increases the mean level of subsequent leisure time physical
      activity in young adulthood but also modifies the genetic and environmental
      variances in leisure time physical activity.

PMID- 29194098
TI  - Greeting From the President.

PMID- 29194099
TI  - Totally Endoscopic Robotic Management of Failed Percutaneous Atrial Septal Defect
      Closure With Tricuspid Valve Injury.
AB  - Totally endoscopic robotic surgery is a safe approach to atrial septal defect
      closure in adults. Robotic approach can be an alternative to traditional
      incisions in the management of concomitant tricuspid valve regurgitation with
      ruptured chordae tendineae. Herein, we describe a woman who presented with atrial
      septal defect and tricuspid insufficiency after an unsuccessful percutaneous
      intervention with device removal from the right ventricle. Concomitant closure of
      septal defect and tricuspid valve repair with artificial chords was successfully
      performed using robot assistance.

PMID- 29194100
TI  - Hematomas in Tiger Territory: An Endovascular Alternative to Wading In.
AB  - A 26-year-old man presented with gunshot wound to the epigastrium. At surgery, he
      was hemodynamically stable and had a tense hematoma with thrill in zone 2 (right
      side) and porta triad. After liver injury was controlled, he underwent
      percutaneous stenting of a renal artery-vena cava fistula and the hepatic artery
      injury was followed. Historically, penetrating injury to zone 2 has mandated
      operative exploration. However, with the advent of endovascular options, in
      stable patients, catheter-based options offer a reasonable alternative with less
      risk of blood loss and possible nephrectomy. Renal artery stenting has been
      advocated for renal artery cava fistulas. The role of timing, hybrid operating
      suites, and traditional operative exposure will vary based on presentation and
      institutional capabilities.

PMID- 29194101
TI  - Impact of an Ultrasonically Activated Device in Robot-Assisted Distal
      Gastrectomy.
AB  - OBJECTIVE: Robot-assisted gastrectomy is increasingly used for the treatment of
      gastric cancer, although it remains a time-consuming procedure. An ultrasonically
      activated device might be useful to shorten operation times. This study therefore
      assessed the effect of ultrasonically activated device use on procedural times
      and on other early surgical outcomes. METHODS: Consecutive patients (N = 42) who
      underwent robot-assisted distal gastrectomy for gastric cancer were included.
      Clinicopathological characteristics and early surgical outcomes were compared
      between robotic-assisted gastrectomy procedures using an ultrasonically activated
      device (U group, n = 21) and those without it (NU group, n = 21). RESULTS: There
      were no significant differences in patient characteristics between the groups;
      however, the median operation time was significantly less in the U group than in
      the NU group (291 vs 351 minutes, P = 0.006). In detail, the median duration of
      console time until dividing the duodenum was less in the U group (70 vs 102
      minutes, P < 0.001). Estimated blood loss, incidence of postoperative morbidity,
      and duration of postoperative hospital stay were not different between the
      groups. CONCLUSIONS: An ultrasonically activated device reduced the operation
      time of robot-assisted gastrectomy without increasing blood loss and morbidity.

PMID- 29194102
TI  - Neurocognitive Profiling of Adult Treatment Seekers Enrolled in a Clinical Trial
      of a Web-delivered Intervention for Substance Use Disorders.
AB  - OBJECTIVE: This study is a secondary descriptive analysis that explores and
      compares the cognitive profiles of adults entering treatment at geographically
      diverse community-based substance use disorder treatment facilities. METHODS:
      Performance on cognitive measures at baseline was compared across 5 primary
      substance subgroups of individuals (alcohol = 104; cocaine = 102; stimulants =
      69; opioids = 108; marijuana = 114) enrolled in a web-based psychosocial
      treatment study conducted within the National Drug Abuse Treatment Clinical
      Trials Network. MicroCog subtests were used to assess cognitive domains of
      attention and mental control, reasoning and cognitive flexibility, and spatial
      processing. RESULTS: The average age of onset for a substance use disorder was
      early to mid-20s, with marijuana users reporting the earliest age of onset (mean
      19.9, SD 7.5) and stimulant users reporting the latest (mean 25.2, SD 9.9). Among
      the total sample, half (49.7%) demonstrated impairment in cognitive flexibility
      and reasoning, and over one-third (37.3%) had impairment in verbal learning and
      memory. Stimulant (37.68%) and cocaine (34.31%) users showed significantly
      greater clinical impairment in attention and mental control compared with alcohol
      users (17.31%) and opioid (21.30%) users (stimulant subgroup only) (chi [4] =
      10.97, P = 0.027). Cocaine users showed the greatest overall impairment across
      total and proficiency subtest scores, although these were not statistically
      different from other subgroups. CONCLUSIONS: These findings confirmed previous
      studies, indicating a high prevalence of significant cognitive dysfunction across
      all substance use categories among treatment-seeking adults, and found that
      cocaine use appears to be associated with the most impairment. Increasing
      knowledge of similarities and differences between primary substance subgroups can
      help guide substance use disorder treatment planning.

PMID- 29194103
TI  - Concerns of Anophthalmic Patients Wearing Cryolite Glass Prosthetic Eyes.
AB  - PURPOSE: To identify the main concerns of patients experienced in wearing
      cryolite glass prosthetic eyes and to investigate how these have changed over
      time. METHODS: One hundred six patients experienced in wearing prosthetic eyes
      for at least 2 years were asked to complete an anonymous questionnaire regarding
      prosthetic eye concerns at the time of initial eye loss and at the present time.
      Main outcome measures included changes in levels of concern over time. RESULTS:
      Initially, the participants were mainly concerned about their appearance, health
      of the fellow eye, and coping with monocularity. Over time, there was a
      significant increase of the level of concern regarding the health of the
      remaining eye (p < 0.001) and regarding watering, crusting, and discharge (p <
      0.001). Loss of balance did not change significantly (p = 0.302). All other
      concerns decreased significantly over time (p < 0.001), with levels of concern
      about appearance decreasing the most. The current leading concern was the health
      of the remaining eye followed by concerns about watering, crusting, and
      discharge. Length of time since natural eye loss was the most important
      explanatory variable, with significant impact on the concerns about appearance (p
      = 0.013), retention of the prosthetic eye (p = 0.002), and eyelid contour (p =
      0.004). CONCLUSIONS: Health of the remaining eye is the most common current
      concern of anophthalmic patients, acknowledging the need of good ophthalmologic
      follow up after losing an eye. The second most important concern is with
      watering, crusting, and discharge, suggesting further research for establishing
      an evidence-based protocol for cryolite glass prosthetic eye maintenance and
      supportive treatment.

PMID- 29194104
TI  - Comparison of Outcomes of 3-Snip Punctoplasty Versus Simple Punctal Dilatation
      With Monocanalicular Intubation for Acquired Punctal Stenosis.
AB  - PURPOSE: To evaluate and compare the outcomes of invasive (rectangular 3-snip
      punctoplasty) versus minimally invasive (punctal dilatation with monocanalicular
      intubation) treatment modalities for the management of acquired punctal stenosis.
      METHODS: A retrospective, comparative, interventional case series was performed
      on 60 eyes of 36 patients with acquired punctal stenosis. Patients were
      categorized in 2 groups based on the intervention as 3-snip punctoplasty (group
      A) and punctal dilatation with monocanalicular intubation (group B). Qualitative
      and quantitative assessment for epiphora and punctal stenosis grading were
      performed preoperatively and postoperatively. Patients with associated
      canalicular and nasolacrimal duct obstructions, congenital punctal disorders,
      eyelid malpositions, and less than 6 months' follow up were excluded. Anatomical
      and functional successes were recorded following stent extubation and at 6-month
      follow up. Statistical analyses were performed using the chi-square, Fisher
      exact, and the Mann-Whitney tests. A p value of <0.05 was considered significant.
      RESULTS: Ninety-nine puncta of 62 eyes of 36 patients were analyzed. Mean age at
      presentation was 49 and 50 years in groups A and B, respectively. Bilaterality
      was noted in 67% (24/36) of the patients. Epiphora was the most common
      presentation. Involvement of upper punctum was noted in 6% (4/62), lower punctum
      in 34% (21/62), and both in 60% (35/62) of eyes. At 6-month follow up, the
      anatomical success rate was 84% (47 out of 56 puncta) in group A, whereas 93% (40
      out of 43 puncta) in group B (p = 0.29). At 6-month follow up, restenosis
      occurred in more number of puncta (n = 9) in group A and only in 3 puncta in
      group B; however, this was not statistically significant (p = 0.21). No stent
      related complications were noted. CONCLUSION: Punctal dilatation with
      monocanalicular intubation achieves comparable outcomes as that of 3-snip
      punctoplasty in patients with acquired punctal stenosis.

PMID- 29194105
TI  - Immune Reconstitution Inflammatory Syndrome in a Case of Nonspecific Orbital
      Inflammation.
AB  - The immune reconstitution inflammatory syndrome is an exaggerated abnormal immune
      response, typically seen in HIV-positive patients following restoration of a
      normal CD4 count as a result of initiation of antiretroviral therapy. It has been
      described in relation to either occult opportunistic infections or to a
      paradoxical relapse of a previously successfully treated infection with negative
      microbiological cultures. The authors report the case of a 60-year-old HIV
      positive African male who presented with 2 episodes of orbital inflammation that
      occurred in conjunction with improvements of CD4 count following Highly Active
      Antiretroviral Therapy. This phenomenon was underpinned by biopsies obtained
      following each episode. Interestingly, on both occasions, he responded well to
      corticosteroid therapy. Although the soft tissues of the orbits are a common area
      affected by other inflammatory diseases, it is rare for them to be involved in
      immune reconstitution inflammatory syndrome. To the authors' knowledge, this is
      the first case report of immune reconstitution inflammatory syndrome affecting
      the orbits exclusively. The authors believe that it is probably an underdiagnosed
      condition and may be erroneously labeled as idiopathic in many cases. This case
      report inspires us to keep an open mind when dealing with patients on
      antiretroviral therapy.

PMID- 29194106
TI  - Increasing Authenticity of Simulation-Based Assessment in Diagnostic Radiology.
AB  - INTRODUCTION: Clinical reasoning in diagnostic imaging professions is a complex
      skill that requires processing of visual information and image manipulation
      skills. We developed a digital simulation-based test method to increase
      authenticity of image interpretation skill assessment. METHODS: A digital
      application, allowing volumetric image viewing and manipulation, was used for
      three test administrations of the national Dutch Radiology Progress Test for
      residents. This study describes the development and implementation process in
      three phases. To assess authenticity of the digital tests, perceived image
      quality and correspondence to clinical practice were evaluated and compared with
      previous paper-based tests (PTs). Quantitative and qualitative evaluation results
      were used to improve subsequent tests. RESULTS: Authenticity of the first digital
      test was not rated higher than the PTs. Test characteristics and environmental
      conditions, such as image manipulation options and ambient lighting, were
      optimized based on participants' comments. After adjustments in the third digital
      test, participants favored the image quality and clinical correspondence of the
      digital image questions over paper-based image questions. CONCLUSIONS: Digital
      simulations can increase authenticity of diagnostic radiology assessments
      compared with paper-based testing. However, authenticity does not necessarily
      increase with higher fidelity. It can be challenging to simulate the image
      interpretation task of clinical practice in a large-scale assessment setting,
      because of technological limitations. Optimizing image manipulation options, the
      level of ambient light, time limits, and question types can help improve
      authenticity of simulation-based radiology assessments.

PMID- 29194107
TI  - Vestibulovaginal Sclerosis Versus Lichen Sclerosus.
AB  - To determine if vestibulovaginal sclerosis and lichen sclerosus (LS) are 2
      distinct entities. Biopsies obtained from the vagina or vulvar vestibule that
      contained abnormal subepithelial collagen were reviewed. Cases were categorized
      either as LS or vestibulovaginal sclerosis based on presence or absence of basal
      layer degeneration and lymphocytic infiltrate. Clinical data collected included
      examination findings, biopsy site and indication, previous vulvovaginal surgery,
      medications at time of biopsy, vulvar LS, treatment, and response. There were 15
      cases with a mean age of 62 yr (range: 32-86 yr); 12 (80%) specimens were from
      vestibule and 3 from vagina. Nine cases were categorized as LS because of
      lymphocytic infiltrate in combination with basal layer degeneration, of these 8
      had LS elsewhere on vulvar skin. Six cases were classified as vestibulovaginal
      sclerosis and had an absent or sparse lymphocytic infiltrate and essentially
      normal epithelium; none of these had vulvar LS. While vestibulovaginal sclerosis
      and lichen sclerosus are distinguishable clinically and histopathologically,
      further studies are needed to determine if vestibulovaginal sclerosis is a subset
      of LS or a different condition.

PMID- 29194109
TI  - Crystalline arthropathy and bone health.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide insight on the
      proposed association between crystal arthritis and bone health. Crystal arthritis
      is the most common type of inflammatory arthritis, and fractures contribute to
      significant morbidity and mortality, therefore, the relationship between the two
      is of clinical importance. RECENT FINDINGS: There have been variable findings
      regarding hyperuricemia, low bone density and risk of fracture. A recent
      systematic review and meta-analysis of available literature showed a correlation
      between increased serum uric acid and lower risk of fracture. Less is known about
      calcium pyrophosphate deposition disease and bone health, although two large
      studies have suggested an association with osteopenia. SUMMARY: A systematic
      review and meta-analysis of available data suggest a correlation between
      increased serum uric acid and lower risk of fracture. Findings support an
      association between bone health and crystal arthritis which warrants further
      study and may have implications for how we treat gout.

PMID- 29194108
TI  - Epigenetics of inflammatory arthritis.
AB  - PURPOSE OF REVIEW: Aberrant epigenetic changes in DNA methylation, histone marks,
      and noncoding RNA expression regulate the pathogenesis of many rheumatic
      diseases. The present article will review the recent advances in the epigenetic
      profile of inflammatory arthritis and discuss diagnostic biomarkers and potential
      therapeutic targets. RECENT FINDINGS: Methylation signatures of fibroblast-like
      synoviocytes not only distinguish rheumatoid arthritis (RA) and osteoarthritis
      (OA), but also early RA from late RA or juvenile idiopathic arthritis.
      Methylation patterns are also specific to individual joint locations, which might
      explain the distribution of joint involvement in some rheumatic diseases.
      Hypomethylation in systemic lupus erythematosus (SLE) T cells is, in part,
      because of active demethylation and 5-hydroxymethylation. The methylation status
      of some genes in SLE is associated with disease severity and has potential as a
      diagnostic marker. An integrative analysis of OA methylome, transcriptome, and
      proteome in chondrocytes has identified multiple-evidence genes that might be
      evaluated for therapeutic potential. Class-specific histone deacetylase
      inhibitors are being evaluated for therapy in inflammatory arthritis. SUMMARY:
      Disease pathogenesis is regulated by the interplay of genetics, environment, and
      epigenetics. Understanding how these mechanisms regulate cell function in health
      and disease has implications for individualized therapy.

PMID- 29194110
TI  - One-Year Retention Study of Adjunctive Perampanel Treatment in Epilepsy Patients.
AB  - OBJECTIVES: Perampanel is a recently introduced antiepileptic drug (AED) with a
      unique action mechanism of noncompetitive and selective alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid antagonist. Because of delayed approval of
      perampanel in most Asian countries, there is limited information on the clinical
      usefulness of perampanel in the Asian population. We performed a retrospective
      analysis of retention rate, seizure outcome, and adverse events for perampanel
      treatment in South Korea. METHODS: This was a retrospective, single-center, 1
      year observational study. A total of 137 epilepsy patients (86 men, 51 women;
      age, 17-86 years) who were treated with perampanel as an adjunctive treatment
      were included. Perampanel was administered at a starting dose of 2 mg/d, and
      optimal-dose adjustments were made according to individual clinical responses.
      Efficacy and tolerability were analyzed during a 1-year follow-up. RESULTS: The
      overall retention rate was 71.3% at the 6-month follow-up and 61.0% at the 1-year
      follow-up. Retention rates were similar between patients with 1 concomitant AED
      and those taking 2 or more concomitant AEDs. The most common adverse event was
      somnolence, followed by dullness and psychiatric reactions, and the presence of
      psychiatric comorbidity was significantly associated with the development of
      psychiatric adverse reactions. CONCLUSIONS: We showed that the retention rate and
      adverse events for adjunctive perampanel treatment in the Korean population were
      comparable with those in Western countries. Our study also suggests that adjuvant
      perampanel treatment may be effective in patients taking a higher number of
      concomitant AEDs and that psychiatric comorbidity may be a risk factor for
      perampanel-induced psychiatric reactions.

PMID- 29194111
TI  - Comment on: Selective Serotonin Reuptake Inhibitor-Induced Hyponatremia: Clinical
      Implications and Therapeutic Alternatives.

PMID- 29194112
TI  - Drug-Associated Spontaneous Orgasm: A Case Report and Systematic Review of
      Literature.
AB  - OBJECTIVES: Spontaneous orgasm is characterized by a spontaneous onset of orgasm
      without any preceding sexual or nonsexual trigger. It sheds insight on the
      mechanisms underlying orgasms and the sexual response cycle in humans. METHODS:
      We report a male patient of repetitive spontaneous orgasm under trazodone
      treatment and systematically review the literature on drug-associated spontaneous
      orgasm (DASO). RESULTS: A total of 25 patients (18 women and 7 men), including
      our reported case, experienced 27 DASO events. Over half of them were under 50
      years of age during the DASO event. Depression was the leading morbidity for
      these patients, and a limited list of antidepressants and antipsychotics were
      involved in 92.5% of all DASO events. Although offending drugs possess variable
      pharmacological properties, their common effect is an augmentation of serotonin
      1A (5HT1A) neurotransmission. Offending drugs seemingly increase personal
      susceptibility to DASO. Over half of the patients, especially men, did not
      concurrently experience sexual arousal or desire during the DASO event. In the
      remaining patients, the orgasm was accompanied by or ensued with arousal or
      desire. A reduction of dose or discontinuation of the offending drug usually
      abolished DASO. CONCLUSIONS: It appears that 5HT1A has a key role in generating
      orgasm. Orgasms may be activated through arousal-independent or arousal-dependent
      pathways, and both orgasms and sexual arousal are bidirectionally activated. This
      double-bidirectional model of sexual response cycle may promote the success of
      sexual procreation and recreation, and further research on this pathway could
      offer an innovative method to manage anorgasmia in the future.

PMID- 29194113
TI  - Anger Assessment in Patients Treated With Brivaracetam.
AB  - OBJECTIVES: To assess state and trait anger, adjusted by epilepsy type, seizure
      control, anxiety-depression status and quality of life, in patients treated with
      brivaracetam (BRV) from an open study. METHODS: We evaluated prospectively
      consecutive patients with partial onset seizures in an open-label study. Patients
      had 5 years or longer of epilepsy and were taking between 1 and 3 antiepileptic
      drugs. They were treated with BRV and compared with a control group selected from
      outpatients attending our epilepsy unit who met the following criteria: age >=16
      years and diagnosis of epilepsy with focal-onset seizures at least 1 year before
      inclusion in the study. The following tests were assessed: State-Trait Anger with
      the Expression Inventory-2, Hospital Anxiety and Depression Scale, and Quality of
      Life in Epilepsy Inventory. RESULTS: We recruited 39 patients, 17 treated with
      BRV and 22 with other drugs, including 13 with levetiracetam (LEV). Mean age was
      47.3 years, 43.6% were men. Symptomatic cases, 66% and 52% temporal lobe
      epilepsy. Antiepileptic drug polytherapy was present in 82.1% of the cases (100%
      BRV vs 68.2% control group). Demographic and clinical characteristics, as well as
      Quality of Life in Epilepsy Inventory and Hospital Anxiety and Depression Scale
      scores were similar in both groups. When compared with the subgroup of LEV groups
      did not differ significantly on their Hospital Anxiety and Depression Scale
      scores. CONCLUSIONS: This small, open study suggests that BRV increases anger
      measures less than LEV in epilepsy patients. However, larger, blinded control
      studies are required to establish whether this apparent difference can be
      confirmed.

PMID- 29194114
TI  - HIV-1 and hepatitis C virus selection bottleneck in Chinese people who inject
      drugs.
AB  - OBJECTIVES: For both HIV-1 and hepatitis C virus (HCV), assessing the stringency
      of the transmission process is a scientific priority. Enumerations of
      transmitted/founder (TF) viruses have shown a strict transmission bottleneck in
      sexual transmission of HIV-1 and a wide range in the multiplicity of infection in
      HCV. Here, we aim to determine the stringency of parenteral transmission for HIV
      1 and HCV in people who inject drugs (PWID). DESIGN: We used molecular sequencing
      and several complementary analyses to enumerate the TF HIV-1 and HCV variants in
      a well described cohort of PWID in Xinjiang, China. METHODS: We performed single
      genome sequencing of HIV-1 env and 5' half HCV genomes, then applied phylogenetic
      analysis and validated models of early virus diversification to enumerate TF
      viruses in 60 PWID. We used multivariate analysis to determine correlates of
      multivariant transmission (MVT). RESULTS: We generated 1070 env region sequences
      from 33 HIV-1 early infected individuals and 773 5' half region sequences from 27
      HCV early infected individuals. We found rates of MVT of 39 and 54%,
      respectively, for HIV-1 and HCV, with a limited range in the number of TF viruses
      in both infections. Behavioural characteristics suggested high-risk injection
      practices and lower risk sexual practices; we did not find an association between
      any specific behaviours and MVT. CONCLUSION: MVT is frequent in parenteral
      transmission of both HIV-1 and HCV in Xinjiang PWID, indicating a less stringent
      transmission process than sexual transmission.

PMID- 29194115
TI  - The validity of self-reported antiretroviral use in persons living with HIV: a
      population-based study.
AB  - OBJECTIVE: To assess the validity of self-reported antiretroviral therapy use
      (ART) using population-based cohort data. METHODS: Self-reported ART use and
      nonuse was compared with a validated laboratory assay in 557 HIV-positive
      participants in the Rakai Community Cohort Study surveyed between September and
      December 2011 in Rakai, Uganda. The study population included participants from
      seven communities, including one fishing community with high HIV prevalence
      (~41%). ART use was assayed using liquid chromatography-tandem mass spectrometry,
      which detects 20 antiretroviral drugs. HIV viral load measurements were also
      obtained. Individuals with at least two antiretroviral drugs detected were
      considered to be using ART. RESULTS: One hundred and fifty-three (27%)
      participants self-reported ART use of whom 148 (97%) had at least two
      antiretroviral drugs detected. There were at least two antiretroviral drugs
      detected in 11% (n = 44/404) of individuals with no self-reported ART use.
      Overall, the specificity of self-reported ART use was 99% (95% CI 97-100%) and
      the sensitivity was 77% (70-83%). Positive and negative predictive values were
      97% (95% CI 93-99%) and 89% (95% CI 86-92%), respectively. Nondisclosure of ART
      use was significantly more common in younger persons (<30 years) and among those
      in trading occupations. CONCLUSION: Self-reported ART use has high specificity
      and moderate sensitivity providing reasonable, but conservative estimates of
      population-based ART use. There is more under-reporting of ART use among younger
      persons and traders suggesting a need for more research on barriers to self
      reporting of ART use in these sub-groups.

PMID- 29194116
TI  - Preexposure prophylaxis guidelines have low sensitivity for identifying
      seroconverters in a sample of young Black MSM in Chicago.
AB  - BACKGROUND: Identification of clients at greatest risk of acquiring HIV is
      critical for preexposure prophylaxi (PrEP) implementation. Young black MSM
      (YBMSM) have high incidence of HIV. We examined published guidelines in
      identifying eligible PrEP candidates, including seroconverters, in a
      representative cohort of YBMSM. METHODS: The uConnect cohort included YBMSM aged
      16-29 years during PrEP roll-out in Chicago from 2013 and 2016. YBMSM with
      indications for PrEP were determined using Center for Disease Control and
      Prevention (CDC) guidelines, the HIV incidence risk index for MSM (HIRI-MSM)
      scoring tool, and Gilead recommendations with calculation of sensitivities,
      specificities, and area under the curve (AUC) for HIV seroconversion over 18
      months. Incidence rate ratios (IRRs) using Poisson regression were modeled to
      compare individual and network factors associated with seroconversion. RESULTS:
      In the study cohort, 300 HIV uninfected YBMSM contributed 390.4 person-years of
      follow-up [mean age (SD), 22.3 years (3.07)]. HIV incidence was 8.5 cases per 100
      person-years (95% confidence interval, 6.0-11.9). One network factor was
      associated with seroconversion: having partners more than 10 years older (IRR =
      4.4, 95% confidence interval, 1.6-11.8). Overall, 49% of the cohort had an
      indication for PrEP using CDC guidelines; 72% using HIRI-MSM, and 86% using
      Gilead recommendations. HIV seroconverters (n = 33) were identified as PrEP
      eligible prior to seroconversion with sensitivities/AUCs for CDC (52%/0.51), HIRI
      MSM (85%/0.57), and Gilead guidelines (94%/0.54). CONCLUSION: Low sensitivity of
      CDC guidelines and limited AUC of HIRI-MSM and Gilead screening tools are of
      concern for PrEP implementation among most at risk populations such as YBMSM.
      Consideration of demographics, local epidemiology, and network factors may better
      guide identification of clients who could benefit most from PrEP.

PMID- 29194117
TI  - Nonsmall cell lung cancer from HIV-infected patients expressed programmed cell
      death-ligand 1 with marked inflammatory infiltrates.
AB  - OBJECTIVE: Immunotherapies targeting the programmed cell death-1 (PD-1)/PD-ligand
      1 (PD-L1) checkpoint improved prognosis in lung cancer. PD-1/PD-L1 status,
      however, has not been investigated in human immunodeficiency virus (HIV)-positive
      patients. This study assessed PD-L1 status and tumor immune-cell infiltration in
      nonsmall cell lung cancer (NSCLC) in HIV patients. METHODS: Consecutive HIV
      patients treated between 1996 and 2014 were enrolled. PD-L1 tumor expression was
      assessed using immunohistochemistry with two antibodies (clones 5H1 and E1L3N),
      and tumor immune-cell infiltration with CD3, CD4, CD8, CD20, CD163, and MPO. PD
      L1 expression and immune infiltration results were compared with those of 54
      NSCLCs from unknown HIV status patients. RESULTS: Thirty-four HIV-positive
      patients were evaluated: predominantly men (88.2%) (median age: 51.1 years)
      presenting stage IV (38.2%) adenocarcinomas (76.5%). The median blood CD4 count
      was 480 cells/MUL (86-1120) and 64% exhibited undetectable viral load. The PD-L1
      score (percentage of positive cells * intensity) was higher in HIV-positive than
      HIV-undetermined patients with the E1L3N clone [median (range) 0 (0-150) versus 0
      (0-26.7), P = 0.047], yet not with the 5H1 clone [0 (0-120) versus 0 (0-26.7) P =
      0.07, respectively]. PD-L1 expression frequency did not differ between both
      cohorts (18.7 versus 9.3% using E1L3N and 10 versus 5.6% using 5H1 clone,
      respectively). There were significantly greater cytotoxic T-cell (P < 0.001), B
      lymphocyte (P = 0.005), and activated macrophage (P < 0.001) infiltrations in the
      HIV-positive patients, but no differences for CD4 T cells. CONCLUSION: Tumors in
      HIV-positive patients seem to express higher PD-L1 levels with increased immune
      infiltration, supporting their inclusion in clinical trials assessing immune
      checkpoint inhibitors.

PMID- 29194118
TI  - Trends in antiretroviral therapy prescription, durability and modification: new
      drugs, more changes, but less failure.
AB  - OBJECTIVE: To evaluate the real world durability of contemporary ART for
      treatment-naive people living with HIV (PLWH). DESIGN: A retrospective follow-up
      study in a multisite cohort. METHODS: This study of the CNICS (CFAR Network of
      Integrated Clinical Systems) cohort integrates data from eight Center for AIDS
      Research (CFARs). PLWH initiating ART between 2007 and 2014 were included.
      Durability was defined as time from the initiation until
      discontinuation/modification using Kaplan-Meier survival curves. Cox Proportional
      Hazards measured associations with various sociodemographic and clinical
      characteristics. RESULTS: Among 5373 PLWH, the initial regimen was modified in
      2285 (43%) patients. Efavirenz/emtricitabine/tenofovir (n = 2173, 40%) was the
      most commonly prescribed initial ART regimen;
      elvitegravir/cobicistat/emtricitabine/tenofovir became more common after 2012.
      Median durability for all regimens was 48.6 months. There were statistically
      significant differences in median durability for NNRTI, InSTI, and protease
      inhibitor-based regimens, which lasted 61, 44, and 32 months, respectively.
      Female sex (aHR = 1.4; 95% CI 1.2-1.6), intravenous drug use (aHR = 1.6; 95% CI
      1.3-1.9), and CD4 cell count less than 200 cells/MUl (aHR = 1.2; 95% CI 1.1-1.3)
      were significantly associated with regimen modification. Compared with InSTI,
      those receiving an InSTI/protease inhibitor (aHR = 2.7; 95% CI 2.0-3.7) or
      protease inhibitor-based ART (aHR = 1.9; 95% CI 1.6-2.2) were significantly more
      likely to be modified; but those receiving NNRTI (aHR = 1.1; 95% CI 0.9-1.3) were
      not. CONCLUSION: In treatment-naive PLWH, NNRTI and InSTI-based ART were most
      durable, relative to protease inhibitor and InSTI/protease inhibitor-based ART,
      and were least likely to be modified/discontinued. A greater understanding of
      reasons for regimen modification/discontinuation is needed to analyze
      contemporary regimen durability.

PMID- 29194119
TI  - Pulmonary disease in HIV-infected adults in the era of antiretroviral therapy.
AB  - : HIV in the antiretroviral therapy era is characterized by multimorbidity and
      the frequent occurrence of HIV-associated non-AIDS chronic health conditions.
      Respiratory symptoms and chronic pulmonary diseases, including chronic
      obstructive pulmonary disease, asthma, and cardiopulmonary dysfunction, are among
      the conditions that may present in persons living with HIV. Tobacco smoking,
      which is disproportionately high among persons living HIV, strongly contributes
      to the risk of pulmonary disease. Additionally, features associated with and at
      times unique to HIV, including persistent inflammation, immune cell activation,
      oxidative stress, and dysbiosis, may also contribute. This review summarizes the
      available literature regarding epidemiology of and risk factors for respiratory
      symptoms and chronic pulmonary disease in the current era.

PMID- 29194120
TI  - Experiences using and organizing HIV self-testing.
AB  - OBJECTIVE: HIV self-testing (HIVST) is now officially recommended by the WHO, yet
      much of HIVST evidence to date has focused on quantitative data and hypothetical
      concerns. Effective scale-up of HIVST in diverse local contexts requires
      qualitative data from experiences using and organizing HIVST. This qualitative
      systematic review aims to appraise and synthesize research evidence on
      experiences using and organizing HIVST. METHODS: We conducted a systematic search
      of seven primary literature databases, four gray literature sources, and
      reference lists reporting qualitative evidence on HIVST. Data extraction and
      thematic analysis were used to synthesize findings. Quality of studies was
      assessed using the Critical Appraisal Skills Programme tool. Confidence in review
      findings was evaluated using the Confidence in the Evidence from Reviews of
      Qualitative Research approach. The review protocol was registered
      (CRD42015027607). RESULTS: From 1266 potential articles, we included 18. Four
      studies were conducted in low-income countries, three in middle-income countries,
      10 in high-income countries, and one in multiple countries. Generally, HIVST
      increased capacity to reach priority populations and expanded opportunities for
      service delivery. Self-testing was preferred to facility-based testing due to
      increased convenience and confidentiality, especially among stigmatized
      populations. HIVST decreased test-associated stigma compared with facility-based
      testing. HIVST generally empowered people because it provided greater control
      over individual testing needs. At the same time, HIVST rarely allowed husbands to
      coerce their wives to test. CONCLUSIONS: This review suggests that HIVST should
      be offered as an additional HIV testing option to expand testing and empower
      testers. Adapting national policies to incorporate HIVST will be necessary to
      guide scale-up.

PMID- 29194121
TI  - HIV-infected cannabis users have lower circulating CD16+ monocytes and IFN-gamma
      inducible protein 10 levels compared with nonusing HIV patients.
AB  - OBJECTIVE: Chronic immune activation and elevated numbers of circulating
      activated monocytes (CD16) are implicated in HIV-associated neuroinflammation.
      The objective was to compare the level of circulating CD16 monocytes and IFN
      gamma-inducible protein 10 (IP-10) between HIV-infected cannabis users (HIV+MJ+)
      and noncannabis users (HIV+MJ-) and determine whether in-vitro Delta
      Tetrahydrocannabinol (THC), a constituent of cannabis, affected CD16 expression
      as well as IP-10 production by monocytes. DESIGN: The levels of circulating CD16
      monocytes and IP-10 from HIV+MJ- and HIV+MJ+ donors were examined. In-vitro
      experimentation using THC was performed on primary leukocytes isolated from HIV
      MJ-, HIV+MJ- and HIV+MJ+ donors to determine if THC has an impact on CD16
      monocyte and IP-10 levels. METHODS: Flow cytometry was used to measure the number
      of blood CD16 monocytes and plasma IP-10 from HIV+MJ- and HIV+MJ+ donors.
      Peripheral blood mononuclear cells were isolated from HIV-MJ- and HIV+ (MJ- and
      MJ+) donors for in-vitro THC and IFNalpha treatment, and CD16 monocytes and
      supernatant IP-10 were quantified. RESULTS: HIV+MJ+ donors possessed a lower
      level of circulating CD16 monocytes and plasma IP-10, compared with HIV+MJ-
      donors. Further, monocytes from HIV+MJ+ donors were unable to induce CD16
      expression when treated with in-vitro IFNalpha, whereas HIV-MJ- and HIV+MJ-
      donors displayed pronounced CD16 induction, suggesting anti-inflammatory effects
      by cannabis. Lastly, in-vitro THC treatment impaired CD16 monocyte transition to
      CD16 and monocyte-derived IP-10. CONCLUSION: Components of cannabis, including
      THC, may decelerate peripheral monocyte processes that are implicated in HIV
      associated neuroinflammation.

PMID- 29194123
TI  - Anti-HIV-1 antibody-dependent cellular cytotoxicity: is there more to antibodies
      than neutralization?
AB  - PURPOSE OF REVIEW: An increasing body of evidence suggests that nonneutralizing
      Fc effector functions including antibody-dependent cellular cytotoxicity (ADCC)
      contribute to protection against HIV-1 acquisition. We discuss recent advances in
      anti-HIV-1 ADCC research with a particular focus on ADCC mediated by Env-specific
      antibodies in vitro and in vivo, the curative potential of HIV-1-specific ADCC
      antibodies and the mechanisms of HIV-1 resistance to ADCC. RECENT FINDINGS: ADCC
      activities of broadly neutralizing and nonneutralizing monoclonal antibody panels
      were recently characterized in vitro against several lab-adapted and primary
      isolates of HIV-1. ADCC activity of these monoclonal antibodies generally
      correlated with binding to infected cells and were greater against the lab
      adapted strains compared with primary HIV-1 isolates. Several recent studies in
      mouse and macaque models of HIV-1 infection suggest Fc-mediated effector
      functions contribute to the protective efficacy of broadly neutralizing
      antibodies and exert immune pressure on HIV-1 in vivo. SUMMARY: An increasing
      body of evidence suggests that ADCC-mediating antibodies, particularly when
      combined with neutralizing functions, can facilitate prevention and control of
      HIV-1. The precise mechanisms of partial protection conferred by nonneutralizing
      antibodies in vivo remain unclear and will need to be fully investigated in order
      to realize their full potential for HIV-1 vaccines.

PMID- 29194122
TI  - Improving postpartum retention in care for women living with HIV in the United
      States.
AB  - : Research findings have consistently demonstrated that women living with HIV in
      the United States and globally experience declines in medication adherence and
      retention in care after giving birth. A number of studies have identified factors
      associated with postpartum retention in care, but the evidence base for
      interventions to address the problem and close this gap in the HIV care continuum
      is limited. Furthermore, the majority of studies have been conducted in low
      resource or moderate-resource countries and may be less applicable or require
      adaptation for use in high resource countries. In the United States, up to two
      thirds of women drop out of care after delivery and are unable to maintain or
      achieve viral suppression postpartum, at a time when maternal and pediatric
      health are closely linked. We conducted a critical review of the literature to
      identify existing gaps regarding maternal retention in the United States and
      conceptualize the problem through the lens of the integrated and ecological
      models of health behavior. This review describes existing barriers and
      facilitators to retention in HIV care postpartum from published studies and
      suggests steps that can be taken, using a multilevel approach, to improve
      maternal retention. We propose five core action steps related to increasing
      awareness of the problem of poor postpartum retention, addressing needs for
      improved care coordination and case management, and using novel approaches to
      adapt and implement peer support and technology-based interventions to improve
      postpartum retention and clinical outcomes of women living with HIV.

PMID- 29194124
TI  - Humanized mouse models to study pathophysiology and treatment of HIV infection.
AB  - PURPOSE OF REVIEW: Immunodeficient mice that lack all lymphocyte subsets and have
      phagocytic cells that are tolerant of human cells can be stably xenografted with
      human hematopoietic stem cell as well as other human tissues (fetal liver and
      thymus) creating 'human immune system' (HIS) mice. HIS mice develop all major
      human lymphocyte classes (B, T, natural killer, and innate lymphoid cell) and
      their specialized subsets as well as a variety of myeloid cells (dendritic cell,
      monocytes, and macrophages) thereby providing a small animal model in which to
      interrogate human immune responses to infection. RECENT FINDINGS: HIS mouse
      models have been successfully used to study several aspects of HIV-1 biology,
      including viral life cycle (entry, restriction, replication, and spread) as well
      as virus-induced immunopathology (CD4 T-cell depletion, immune activation, and
      mucosal inflammation). Recent work has shown that HIV reservoirs can be
      established in HIV-infected HIS mice after treatment with combinations of
      antiretroviral drugs thereby providing a model to test new approaches to
      eliminate latently infected cells. SUMMARY: HIS mice provide cost-effective
      preclinical platform to assess combination immunotherapies that can target HIV
      reservoirs. Therapeutic strategies validated in HIS mice should be considered in
      designing the roadmap toward HIV 'cure'.

PMID- 29194125
TI  - NaV1.7 and pain: contribution of peripheral nerves.
AB  - The sodium channel NaV1.7 contributes to action potential (AP) generation and
      propagation. Loss-of-function mutations in patients lead to congenital
      indifference to pain, though it remains unclear where on the way from sensory
      terminals to central nervous system the signalling is disrupted. We confirm that
      conditional deletion of NaV1.7 in advillin-expressing sensory neurons leads to
      impaired heat and mechanical nociception in behavioural tests. With single-fiber
      recordings from isolated skin, we found (1) a significantly lower prevalence of
      heat responsiveness to normally mechanosensitive C-fibers, although (2) the rare
      heat responses seemed quite vigorous, and (3) heat-induced calcitonin gene
      related peptide release was normal. In biophysical respects, although electrical
      excitability, rheobase, and chronaxy were normal, (4) axonal conduction velocity
      was 20% slower than in congenic wild-type mice (5) and when challenged with
      double pulses (<100 milliseconds interval), the second AP showed more pronounced
      latency increase (6). On prolonged electrical stimulation at 2 Hz, (7) activity
      dependent slowing of nerve fiber conduction was markedly less, and (8) was less
      likely to result in conduction failure of the mutant single fibers. Finally,
      recording of compound APs from the whole saphenous nerve confirmed slower
      conduction and less activity-dependent slowing as well as the functional absence
      of a large subpopulation of C-fibers (9) in conditional NaV1.7 knockouts. In
      conclusion, the clear deficits in somatic primary afferent functions shown in our
      study may be complemented by previously reported synaptic dysfunction and
      opioidergic inhibition, together accounting for the complete insensitivity to
      pain in the human mutants lacking NaV1.7.

PMID- 29194126
TI  - Machine learning in pain research.

PMID- 29194128
TI  - The Connected Age of Health Care: Will Nurse Educators Rise to the Challenge?
AB  - : As a leader in nursing education reform, the NLN strives to be at the forefront
      of the issues affecting the lives of nurse educators. Our ultimate goal is to
      advance the health of the nation and the global community.

PMID- 29194129
TI  - Peer Review: The Science of Nursing Education Depends on It.
AB  - : In my three years as editor of the Research Briefs section of Nursing Education
      Perspectives, I have worked with many stellar reviewers and have learned a
      significant amount about peer review.

PMID- 29194127
TI  - Core outcome measurement instruments for clinical trials in nonspecific low back
      pain.
AB  - To standardize outcome reporting in clinical trials of patients with nonspecific
      low back pain, an international multidisciplinary panel recommended physical
      functioning, pain intensity, and health-related quality of life (HRQoL) as core
      outcome domains. Given the lack of a consensus on measurement instruments for
      these 3 domains in patients with low back pain, this study aimed to generate such
      consensus. The measurement properties of 17 patient-reported outcome measures for
      physical functioning, 3 for pain intensity, and 5 for HRQoL were appraised in 3
      systematic reviews following the COSMIN methodology. Researchers, clinicians, and
      patients (n = 207) were invited in a 2-round Delphi survey to generate consensus
      (>=67% agreement among participants) on which instruments to endorse. Response
      rates were 44% and 41%, respectively. In round 1, consensus was achieved on the
      Oswestry Disability Index version 2.1a for physical functioning (78% agreement)
      and the Numeric Rating Scale (NRS) for pain intensity (75% agreement). No
      consensus was achieved on any HRQoL instrument, although the Short Form 12 (SF12)
      approached the consensus threshold (64% agreement). In round 2, a consensus was
      reached on an NRS version with a 1-week recall period (96% agreement). Various
      participants requested 1 free-to-use instrument per domain. Considering all
      issues together, recommendations on core instruments were formulated: Oswestry
      Disability Index version 2.1a or 24-item Roland-Morris Disability Questionnaire
      for physical functioning, NRS for pain intensity, and SF12 or 10-item PROMIS
      Global Health form for HRQoL. Further studies need to fill the evidence gaps on
      the measurement properties of these and other instruments.

PMID- 29194130
TI  - Competencies for Leaders in Nursing Education.
AB  - AIM: The study purpose was to identify and describe the competencies that
      educators need to be leaders in nursing education. BACKGROUND: Leadership is
      inherent within the role of the nurse educator; however, many lack formal
      education in leadership and are underprepared to fully embrace the faculty
      leadership role. there exists a dearth of research on the competencies necessary
      for leaders in nursing education. METHOD: Fifteen leaders in nursing education
      were interviewed. Data were analyzed using an inductive iterative process.
      trustworthiness was established. FINDINGS: Four competencies emerged: articulate
      and promote a vision for nursing education, function as a steward for the
      organization and nursing education, embrace professional values in the context of
      higher education, develop and nurture relationships. CONCLUSION: Leadership is an
      essential component of the nurse educator role. The findings provide evidence to
      support best practices in nursing education and to advance the science of nursing
      education.

PMID- 29194131
TI  - Narrative Pedagogy: Transforming Nursing Education Through 15 Years of Research
      in Nursing Education.
AB  - AIM: This article provides a review of current disciplinary understanding of
      Narrative Pedagogy and describes the implications for ongoing transformation in
      nursing education. BACKGROUND: Narrative Pedagogy has been enacted and
      investigated by teachers around the world for more than 15 years. Few nursing
      educational innovations or pedagogies in nursing have been adopted in such an
      array of settings/levels. METHOD: A review of the nursing literature was
      conducted to locate reports of research on and teaching innovations derived from
      Narrative Pedagogy. RESULTS: Narrative Pedagogy has an extensive and longitudinal
      body of research describing how the approach contributes to the educational
      transformation the discipline seeks. CONCLUSION: Narrative Pedagogy and the
      growing literature describing how it is enacted provides a way for teachers and
      students to persist in questioning their current understanding of nursing, the
      ways they think about the situations they encounter, and how their practice can
      best be learned.

PMID- 29194132
TI  - Reflections of Evidence-Based Practice in Nurse Educators' Teaching Philosophy
      Statements.
AB  - AIM: This article focuses on the nature and importance of evidence-based practice
      (EBP) as described in the teaching philosophy statements of academic nurse
      educators (ANEs). BACKGROUND: EBP is a core competency identified by the
      Institute of Medicine. Its incorporation into teaching philosophies expresses
      ANEs' ideas, values, and practices. METHOD: A mixed-method design using an online
      survey was used to collect and analyze demographic data and teaching philosophy
      statements from 375 ANEs. Coding was done via direct correct analysis. Themes
      were identified to capture the essence of the coded statements. RESULTS: EBP and
      its components were mentioned 275 times collectively; 44 ANEs specifically
      mentioned EBP in their teaching philosophies. other components were mentioned
      more frequently. three themes emerged: keeping up-to-date, setting up student
      success with EBP, and EBP as a teaching approach. CONCLUSION: The incorporation
      of EBP and its components was not widely acknowledged by ANEs.

PMID- 29194133
TI  - Nurse Residency Programs: An integrative Review of the Literature.
AB  - AIM: The aim is to explore nurse residency programs described in the literature
      and evaluate the evidence supporting their use. BACKGROUND: The Institute of
      medicine and the Joint Commission recommend that organizations provide nurse
      residency programs for newly licensed nurses. METHOD: An integrative review was
      conducted of empirical and program development articles published from 2006 to
      july 2013. RESULTS: Most articles included in this study had limitations, which
      are discussed. CONCLUSION: The literature demonstrates benefits associated with
      NRPs. More evidence is needed to determine if NRPs contribute to nurse-sensitive
      patient outcomes, thereby influencing quality of nursing care.

PMID- 29194134
TI  - Competence Acquisition Using Simulated Learning Experiences: A Concept Analysis.
AB  - AIM: To report the findings of an analysis of the concept of competence
      acquisition when determined using simulated learning experiences. BACKGROUND:
      Competence of nursing students prior to entry into practice has been stressed by
      the Institute of Medicine. Competence can be evaluated via simulation; however,
      evaluation practices vary among schools of nursing. The link between competence
      acquisition in simulation and clinical competence has not been determined.
      METHOD: Employing the methodology of , articles included in this analysis were
      published in english in peer-reviewed journals from 2002 to 2012 and contained
      information on simulation outcomes related to competence. Thirty-five articles
      and one text were included in the final analysis. RESULTS: Essential elements of
      competence acquisition identified included authentic environment, demonstration,
      and evaluation. CONCLUSION: Use of a consistent language and framework to
      evaluate competence acquisition in simulation is recommended, as is future
      research to test the constructs.

PMID- 29194135
TI  - Complexity of Care: A Concept Analysis of Older Adult Health Care Experiences.
AB  - PURPOSE: To define the term complexity of care. BACKGROUND: The aging population
      and lack of gerontological preparation in pre-licensure nursing programs are
      pressing issues. The NLN Advancing Care Excellence for Seniors (ACE.S) project
      developed a framework to facilitate faculty and student understanding of older
      adults' care needs. Integral to the framework is the concept of complexity of
      care. METHOD: Rogers and Knafl's evolutionary method of concept analysis was
      used. RESULTS: The analysis identified three antecedents (focus on treatment and
      cure of disease, multiple comorbidities, and life experiences and culture), five
      attributes (polypharmacy, use of advanced technologies, novel care models, a
      fragmented health care system, and the relational nature of caregiving), and two
      consequences (impact on quality of life and impact on quality of care).
      CONCLUSION: Defining the concept of complexity of care will facilitate student
      understanding of the unique health care needs of older adults.

PMID- 29194136
TI  - Flipped Versus Traditional Instruction and Achievement in a Baccalaureate Nursing
      Pharmacology Course.
AB  - : The researchers used a quantitative pretest-posttest nonequivalent control
      group quasi-experimental design to determine if there is a significant difference
      in content knowledge acquisition between traditional and flipped classroom
      methods. Analysis revealed that the flipped classroom approach was significantly
      different for three unit exams. The results did not show a significant difference
      in the means for the final exam. Knowledge gains on tests and students' positive
      responses support the use of the flipped classroom method.

PMID- 29194137
TI  - Measuring Confidence in Nursing Graduates Within the Framework of the AACN
      Essentials.
AB  - : The American Association of Colleges of Nursing (AACN) Essentials of
      Baccalaureate Education provide a framework for assessment of nursing programs.
      The purpose of this pilot study was to determine if there was a difference in
      self-perceived confidence in meeting the AACN essentials between senior students
      who completed a traditional clinical course and those in a preceptorship course.
      A descriptive, comparative design was used. The results indicate that students
      who completed both course models had similarly high levels of perceived
      confidence in meeting the majority of the AACN essentials.

PMID- 29194138
TI  - Learner Perception, Expected Competence, and Satisfaction of Team-Based Learning
      in Korean Nursing Students.
AB  - : The purpose of this study was to describe learner perception, expected
      competence, and factors influencing satisfaction with team-based learning in a
      nursing course. Four-hour TBL sessions were given in a structured three-phase
      sequence for a cohort of 139 second-year nursing students. TBL was found to be an
      effective instructional strategy inducing team learning and self-directed
      learning. Nursing educators should improve TBL quality by focusing on the student
      team learning process.

PMID- 29194139
TI  - Nursing as an Additional Language and Culture (NALC): Supporting Student Success
      in a Second-Degree Nursing Program.
AB  - : The nursing workforce does not represent the diversity of the United States
      population and while recruitment of diverse nursing students is high, so are
      their rates of attrition. The Nursing as an Additional Language and Culture
      Program (NALC) was implemented in an accelerated, second-degree baccalaureate
      nursing program to enhance retention by minimizing barriers and supporting
      activities to enhance student success. Results suggest that the NALC program was
      successful in decreasing the attrition rate of nursing students, including
      minority students.

PMID- 29194140
TI  - High-Fidelity Simulation for Senior Maternity Nursing Students.
AB  - : This retrospective study examined the effectiveness of high-fidelity simulation
      (HFS) in a senior maternity baccalaureate nursing program. The study specifically
      focused on whether students who received instruction through HFS in addition to
      traditional hospital-based clinical instruction achieved greater practical
      learning, critical thinking skills, and NCLEX performance potential. Bandura's
      theory of self-efficacy guided the study. Simulation students (n = 132) were
      found to score significantly better than nonsimulation students (n = 147) in each
      area. Use of HFS may foster the development of competent and clinically prepared
      nurses.

PMID- 29194141
TI  - Navigating Evidence-Based Practice Projects: The Faculty Role.
AB  - : An innovative way to facilitate evidence-based practice (EBP) learning and to
      get evidence into practice is through academic-clinical agency projects involving
      faculty, undergraduate students, and agency staff. The central role of the
      faculty is key to successful academic-clinical agency partnerships. Faculty
      navigate the often difficult process of focusing students and engaging busy staff
      through initiating, maintaining, and evaluating projects. Students learn valuable
      EBP skills, staff become engaged in EBP, and the projects are rated highly by
      agency administrators.

PMID- 29194142
TI  - Connected Health 2015: The Year of Virtual Patient Visits.

PMID- 29194143
TI  - NLN Releases A Vision for the Changing Faculty Role: Preparing Students for the
      Technological World of Health Care.

PMID- 29194144
TI  - Thoracic Epidural Analgesia and Mortality in Acute Pancreatitis: A Multicenter
      Propensity Analysis.
AB  - OBJECTIVE: Recent preclinical and clinical data suggest that thoracic epidural
      analgesia, a technique primarily aimed at decreasing pain, might exert anti
      inflammatory effects, enhance splanchnic and pancreatic blood flow during acute
      pancreatitis; however, the influence of epidural analgesia on mortality remains
      under investigated in this setting. This study was therefore designed to assess
      the impact of epidural analgesia on mortality in ICU patients with acute
      pancreatitis. DESIGN: Multicenter retrospective, observational, cohort study.
      SETTING: Seventeen French and Belgian ICUs. PATIENTS: All patients admitted to
      with acute pancreatitis between June 2009 and March 2014. INTERVENTIONS: The
      primary exposure was thoracic epidural analgesia versus standard care without
      epidural analgesia. The primary outcome was 30-day mortality. Propensity analyses
      were used to control for bias in treatment assignment and prognostic imbalances.
      MEASUREMENTS AND MAIN RESULTS: One thousand three ICU patients with acute
      pancreatitis were enrolled, of whom 212 died within 30 days. Epidural analgesia
      was used in 46 patients and was associated with reduced mortality in unadjusted
      analyses (4% vs. 22%; p = 0.003). After adjustment for baseline variables
      associated with mortality, epidural analgesia was still an independent predictor
      of 30-day mortality (adjusted odds ratio, 0.10; [95% CI, 0.02-0.49]; p = 0.004).
      Using propensity score analysis, the risk of all-cause 30-day mortality in
      patients with acute pancreatitis receiving epidural analgesia was significantly
      lower than that in matched patients who did not receive epidural analgesia (2%
      vs. 17%; p = 0.01). CONCLUSIONS: Among critically ill patients with acute
      pancreatitis, mortality at 30 days was lower in patients who received epidural
      analgesia than in comparable patients who did not. These findings support ongoing
      research on the use of epidural analgesia as a therapeutic intervention in acute
      pancreatitis.

PMID- 29194145
TI  - Continuous Infusion of Low-Dose Iohexol Measures Changing Glomerular Filtration
      Rate in Critically Ill Patients.
AB  - OBJECTIVE: Measurement of changing glomerular filtration rate in acute kidney
      injury remains problematic. We have previously used a continuous infusion of low
      dose Iohexol to measure glomerular filtration rate in stable subjects and
      postulate that changes greater than 10.3% in critically ill patients indicate
      acute kidney injury. Our objective is to explore the extent to which continuous
      infusion of low-dose Iohexol can be a measure of changing glomerular filtration
      rate during acute kidney injury. DESIGN: Clinical observational exploratory
      study. SETTING: Adult ICU. PATIENTS: Three patient groups were recruited:
      nephrectomy group: predictable onset of acute kidney injury and outcome (n = 10);
      surgery group: predictable onset of acute kidney injury, unpredictable outcome (n
      = 11); and acute kidney injury group: unpredictable onset of acute kidney injury
      and outcome (n = 13). INTERVENTIONS: Continuous infusion of low-dose Iohexol was
      administered for 24-80 hours. Plasma (ClP) and renal (ClR) Iohexol clearances
      were measured at timed intervals. MEASUREMENTS AND MAIN RESULTS: Kidney Disease:
      Improved Global Outcomes acute kidney injury criteria were fulfilled in 22
      patients (nephrectomy = 5, surgery = 4, and acute kidney injury = 13); continuous
      infusion of low-dose Iohexol demonstrated acute kidney injury in 29 patients
      (nephrectomy = 10, surgery = 8, acute kidney injury = 11). Dynamic changes in
      glomerular filtration rate were tracked in all patients. In the nephrectomy
      group, ClR decreased by an expected 50% (50.8% +/- 11.0%). Agreement between ClP
      and ClR improved with increasing duration of infusion: bias of ClP versus ClR at
      48 hours was -0.1 +/- 3.6 mL/min/1.73 m (limits of agreement: -7.2 to 7.1
      mL/min/1.73 m). Coefficient of variation of laboratory sample analysis was 2.4%.
      CONCLUSIONS: Continuous infusion of low-dose Iohexol is accurate and precise when
      measuring glomerular filtration rate and tracks changes in patients with
      differing risks of acute kidney injury. Continuous infusion of low-dose Iohexol
      may provide a useful standard against which to test novel biomarkers for the
      diagnosis of acute kidney injury.

PMID- 29194146
TI  - Risk Factors of Impaired Neuropsychologic Outcome in School-Aged Survivors of
      Neonatal Critical Illness.
AB  - OBJECTIVE: Until now, long-term outcome studies have focused on general cognitive
      functioning and its risk factors following neonatal extracorporeal membrane
      oxygenation and/or congenital diaphragmatic hernia. However, it is currently
      unknown which neuropsychological domains are most affected in these patients and
      which clinical variables can be used to predict specific neuropsychological
      problems. This study aimed to identify affected neuropsychological domains and
      its clinical determinants in survivors of neonatal extracorporeal membrane
      oxygenation and/or congenital diaphragmatic hernia. DESIGN: Prospective follow-up
      study. SETTING: Tertiary university hospital. PATIENTS: Sixty-five 8-year-old
      survivors of neonatal extracorporeal membrane oxygenation and/or congenital
      diaphragmatic hernia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Intelligence, attention, memory, executive functioning and visuospatial
      processing were evaluated using validated tests and compared with Dutch reference
      data. Assessed risk factors of outcome were illness severity indicators, number
      of anesthetic procedures in the first year of life, and growth at 1 year.
      Patients had average intelligence (mean intelligence quotient +/- SD, 95 +/- 16),
      but significantly poorer sustained attention (mean z score +/- SD, -2.73 +/-
      2.57), verbal (immediate, -1.09 +/- 1.27; delayed, -1.14 +/- 1.86), and
      visuospatial memory (immediate, -1.48 +/- 1.02; delayed, -1.57 +/- 1.01;
      recognition, -1.07 +/- 3.10) than the norm. Extracorporeal membrane oxygenation
      treated congenital diaphragmatic hernia patients had significantly lower mean
      intelligence quotient (84 +/- 12) than other neonatal extracorporeal membrane
      oxygenation patients (94 +/- 10) and congenital diaphragmatic hernia patients not
      treated with extracorporeal membrane oxygenation (100 +/- 20). Maximum vasoactive
      inotropic score was negatively associated with delayed verbal (B = -0.02; 95% CI,
      -0.03 to -0.002; p = 0.026) and visuospatial memory (B = -0.01; 95% CI, -0.02 to 
      0.001; p = 0.024). CONCLUSIONS: We found memory and attention deficits in 8-year
      old neonatal extracorporeal membrane oxygenation and congenital diaphragmatic
      hernia survivors. The maximum dose of vasoactive medication was negatively
      associated with verbal and visuospatial memory, which may suggest an effect of
      early cerebral hypoperfusion in determining these abnormalities.

PMID- 29194147
TI  - Severity of Illness Scores May Misclassify Critically Ill Obese Patients.
AB  - OBJECTIVE: Severity of illness scores rest on the assumption that patients have
      normal physiologic values at baseline and that patients with similar severity of
      illness scores have the same degree of deviation from their usual state. Prior
      studies have reported differences in baseline physiology, including laboratory
      markers, between obese and normal weight individuals, but these differences have
      not been analyzed in the ICU. We compared deviation from baseline of pertinent
      ICU laboratory test results between obese and normal weight patients, adjusted
      for the severity of illness. DESIGN: Retrospective cohort study in a large ICU
      database. SETTING: Tertiary teaching hospital. PATIENTS: Obese and normal weight
      patients who had laboratory results documented between 3 days and 1 year prior to
      hospital admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seven
      hundred sixty-nine normal weight patients were compared with 1,258 obese
      patients. After adjusting for the severity of illness score, age, comorbidity
      index, baseline laboratory result, and ICU type, the following deviations were
      found to be statistically significant: WBC 0.80 (95% CI, 0.27-1.33) * 10/L; p =
      0.003; log (blood urea nitrogen) 0.01 (95% CI, 0.00-0.02); p = 0.014; log
      (creatinine) 0.03 (95% CI, 0.02-0.05), p < 0.001; with all deviations higher in
      obese patients. A logistic regression analysis suggested that after adjusting for
      age and severity of illness at least one of these deviations had a statistically
      significant effect on hospital mortality (p = 0.009). CONCLUSIONS: Among patients
      with the same severity of illness score, we detected clinically small but
      significant deviations in WBC, creatinine, and blood urea nitrogen from baseline
      in obese compared with normal weight patients. These small deviations are likely
      to be increasingly important as bigger data are analyzed in increasingly precise
      ways. Recognition of the extent to which all critically ill patients may deviate
      from their own baseline may improve the objectivity, precision, and
      generalizability of ICU mortality prediction and severity adjustment models.

PMID- 29194148
TI  - Moving Beyond Our Comfort Zone to Propel Nursing Education Toward Reform and
      Transformation.
AB  - : Happy New Year, colleagues. As 2015 begins and we contemplate reform in nursing
      education, it is instructive to reflect on events of our recent past.

PMID- 29194149
TI  - Predatory Journals: What Nurse Educators Need to Know.
AB  - : At the 2014 annual meeting of the International Academy of Nurse Editors,
      journal editors agreed to collectively address the issue of predatory journals,
      especially those in nursing, in order to better inform our authors, readers, and
      reviewers.

PMID- 29194150
TI  - English-Language Proficiency, Academic Networks, and Academic Performance of
      Mexican American Baccalaureate Nursing Students.
AB  - AIM: We examine how academic networks mediate between English-language
      proficiency and academic performance. BACKGROUND: The relationship between
      English-language proficiency and academic performance remains inconclusive; it is
      possible that academic networks play a role in this relationship. Filling this
      knowledge gap is central to building best practices in teaching, and to
      evaluating the impact of networks on success. METHOD: Data were analyzed from 164
      Mexican American nursing students. We used English Language Acculturation Scale
      (ELAS) items as predictors, interaction with academic networks as the mediating
      variable, and course grade as the outcome; regression analyses were performed.
      RESULTS: Interaction with academic networks correlated with grades; ELAS was not
      significant. Instead, academic networks mediated between entrance GPA and grades,
      an unexpected finding. CONCLUSION: Academic networks are critical in academic
      performance. However, only those students who have a history of high performance
      are likely to have or to activate academic networks.

PMID- 29194151
TI  - A Correlational Study of a Reading Comprehension Program and Attrition Rates of
      ESL Nursing Students in Texas.
AB  - AIM: The purpose of this study was to examine the associations between English as
      a second language (ESL), a reading comprehension program, and attrition rates of
      nursing students. BACKGROUND: Higher attrition rates of ESL nursing students are
      an assumption, seemingly based on anecdotal evidence. Data reflecting ESL student
      attrition should be measured and analyzed so that students can be identified
      prior to attrition. METHOD: A secondary analysis of a large database of 27
      initial licensure programs in Texas was completed. RESULTS: Data analysis
      identified that ESL students who used a reading comprehension program were almost
      twice as likely to be off track or out of the program as ESL students who did not
      use the program. CONCLUSION: Nurse educators need to evaluate student profile
      characteristics in a comprehensive way when determining risk of attrition.

PMID- 29194153
TI  - Nursing Student Satisfaction with an Associate Nursing Program.
AB  - PURPOSE: The purpose of this study was to conduct a nationwide survey to
      understand the satisfaction of associate of science in nursing (ASN) students
      with a nursing program as a whole. BACKGROUND: Student satisfaction is viewed as
      an indicator of program success. Yet, nursing student satisfaction has not been
      sufficiently studied in the United States. METHOD: The Curriculum, Faculty,
      Social Interaction, and Environment model was used to support this nationwide
      study. Stratified random sampling was used to recruit 56 ASN programs from 31 US
      states for participation. RESULTS: The students rated their satisfaction with the
      nursing program as close to "satisfied." The faculty, curriculum, and social
      interaction significantly and positively predicted overall student satisfaction
      with a nursing program. CONCLUSION: A nursing program can evaluate students'
      satisfaction periodically to determine the impact of the educational experience
      on the program's performance.

PMID- 29194152
TI  - Cultural Competence in Rural Nursing Education: Are We There Yet?
AB  - AIM: This multimethod study assessed the capacity of nursing education programs
      to promote culturally congruent practice in a single rural state. BACKGROUND: An
      important objective of our HRSA-funded Advanced Education in Nursing grant was to
      increase nurse educator proficiency in teaching cultural concepts. This study
      served as a statewide baseline assessment to inform future faculty development
      efforts. METHOD: Subjects included faculty, graduate students, and clinical
      educators representing all levels of nursing education programs. Self-report
      cultural proficiency data were collected via survey while focus groups and
      electronic surveys were utilized to assess curricula. RESULTS: No significant
      differences in proficiency were found by faculty age or education. Qualitative
      data indicated that concepts of culture are not easily identified across the
      curriculum. CONCLUSION: There is need for increased and explicit focus on
      concepts of culture in nursing education programs to prepare nurses for
      culturally congruent practice with potential to reduce health disparities.

PMID- 29194154
TI  - Facilitating Educational Advancement of RNs to the Baccalaureate: What Are They
      Telling Us?
AB  - AIM: This metasynthesis assists in the interpretation of qualitative research
      performed to explore the experience of registered nurses who return to school to
      pursue a baccalaureate degree. Understanding these experiences is necessary to
      achieve the national goal of 80 percent of RNs having BSNs by 2020. BACKGROUND:
      As few as 21 percent of all RNs prepared at the associate or diploma level earn a
      baccalaureate degree. Experts believe that enhanced academic-clinical
      partnerships can result in an improvement. METHOD: Noblit and Hare's method was
      followed to increase understanding of the phenomena. RESULTS: Seven overarching
      themes are presented in the words of the 324 nurses included in the 13
      qualitative studies in the sample. CONCLUSION: The experiences of these nurses
      provide information to inform partnerships for the development of effective,
      efficient, and meaningful educational pathways that acknowledge the challenges
      and needs of these professionals.

PMID- 29194155
TI  - Factors Influencing Retention Among Part-Time Clinical Nursing Faculty.
AB  - AIM: This study sought to determine job characteristics influencing retention of
      part-time clinical nurse faculty teaching in pre-licensure nursing education.
      BACKGROUND: Large numbers of part-time faculty are needed to educate students in
      the clinical setting. Faculty retention helps maintain consistency and may
      positively influence student learning. METHOD: A national sample of part-time
      clinical nurse faculty teaching in baccalaureate programs responded to a web
      based survey. Respondents were asked to identify the primary reason for wanting
      or not wanting to continue working for a school of nursing (SON). RESULTS:
      Affinity for students, pay and benefits, support, and feeling valued were the top
      three reasons given for continuing to work at an SON. Conflicts with life and
      other job responsibilities, low pay, and workload were the top three reasons
      given for not continuing. CONCLUSION: Results from this study can assist nursing
      programs in finding strategies to help reduce attrition among part-time clinical
      faculty.

PMID- 29194156
TI  - Graduate-Entry Non-Nursing Students: Is Emotional Intelligence the Difference?
AB  - : Despite numerous measures of their success, nurses from graduate nursing
      programs for non-nurses (GPNNN) often struggle to find acceptance in the
      workplace. Employers frequently describe these nurses' superior psycho/social
      capabilities when compared to traditionally educated nurses, but little
      substantiating quantitative data exist to support this. This study explored
      nursing students' psycho/social ability by comparing measured emotional
      intelligence (EI) ability among students from four nursing schools, including one
      GPNNN program. Findings included significantly higher scores in the EI subscore
      "understanding emotions" for GPNNN students over two of the three comparison
      nursing programs, even when data were controlled for age.

PMID- 29194157
TI  - The Effect of Simulation Training on Baccalaureate Nursing Students' Competency
      in Performing Intramuscular Injection.
AB  - : This research study addressed BSN student competency in administering
      intramuscular injections with and without simulation training, and ability to
      transfer the skill from learning laboratory to patient care. There is a dearth of
      empirical evidence supporting simulation in psychomotor skill learning and
      transfer of these skills to patient care. A two-group repeated measures
      pretest/posttest design with three measurement times was used. Scenario-based
      simulation served as the intervention. All subjects were posttested in the
      learning laboratory and clinical settings. The experimental group had higher
      adjusted means at both posttesting times, though these results were not
      statistically significant.

PMID- 29194158
TI  - Doing Learning Knowing Speaking: How Beginning Nursing Students Develop Their
      Identity as Nurses.
AB  - : The purpose of this pilot study was to analyze beginning nursing students'
      stories to understand how students develop a sense of being a nurse while
      pursuing a nursing degree. The study was a secondary analysis with a
      nonexperimental descriptive design. The setting was a rural private liberal arts
      campus. The sample was a purposive sample of 10 sophomore nursing students
      enrolled in an introductory nursing class. One major theme was identified. Doing
      Learning Knowing Speaking emerged as the way students begin to develop their
      professional nursing identity and feel like a nurse.

PMID- 29194159
TI  - Evaluating Nurse Practitioner Students Through Objective Structured Clinical
      Examination.
AB  - : Medical schools' use of Objective Structured Clinical Examination (OSCE) for
      over 30 years proves the OSCE is an objective way to assess a variety of clinical
      skills. This pilot study determined the feasibility of using OSCE, together with
      a checklist tool, to evaluate nurse practitioner (NP) students' competency in
      obtaining a patient's health history and performing a complete physical
      examination. In this descriptive study, four NP faculty viewed a prerecorded OSCE
      video of a student/ patient encounter and scored it using a checklist to
      determine the student's competency. Faculty showed a strong degree of agreement
      in grading competence. Findings suggest OSCEs could be an effective means of
      student evaluation, but revising the checklist to align with NP national
      competencies would make it meaningful for NP evaluation specifically.

PMID- 29194160
TI  - Improving NCLeX-RN First-Time Pass Rates with a Balanced Curriculum.
AB  - : The comprehensive changes made to the school of nursing's curriculum have
      allowed the educators and students to experience several positive outcomes. This
      article describes the challenges faced by the school of nursing in the past four
      years and the collaborative practices that the faculty and students have engaged
      in that have culminated in an improved NCLEX-RN first-time pass rate.

PMID- 29194161
TI  - BSN Admission Group Interviews: Perceptions of Students, Faculty, and Community
      Nurses.
AB  - : To assist in the selection students for a baccalaureate program, a school of
      nursing instituted a group interview process. An exploratory qualitative design
      was used to assess faculty, community nurse, and student perceptions of the
      process. Faculty, community nurses, and students who participated in interviews
      were asked to complete a five-item, open-ended survey. Data analysis revealed
      that they enjoyed the process and identified it as beneficial. A positive aspect
      included students' getting to present themselves as more than a GPA. The use of
      group interviews provides additional information for faculty who are challenged
      with selecting students for enrollment in programs of nursing.

PMID- 29194162
TI  - Implementing a Pediatric Camp Clinical for Pre-Licensure Education.
AB  - : This article describes the implementation and outcomes of a pediatric clinical
      education pilot project at a weekend overnight camp for children with special
      needs. Nine junior-level baccalaureate students participated in the immersion
      experience. The course skill inventory, an instructor-led postconference, a focus
      group session, and online forum entries were used to evaluate the experience. The
      evidence suggests that students gained a wide variety of psychomotor skills and
      patient-centered care attitudes. Although scheduling was challenging, we
      concluded the camp clinical was an enlightening and positive experience that
      offered opportunities not readily available in the hospital setting.

PMID- 29194163
TI  - Health Technology Predictions for 2015:Ringing in the New.

PMID- 29194164
TI  - Grant from Independence Blue Cross Foundation Expands NLN's Advancing Care
      Excellence for Seniors (Ace.s) Resources to Practice Environments.

PMID- 29194165
TI  - Clinical Characteristics and Risk Factors of Long-term Central Venous Catheter
      associated Bloodstream Infections in Children.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) account for
      significant morbidity and mortality in patients with long-term central venous
      catheters (CVCs). This study was performed to identify the characteristics and
      risk factors of CLABSIs among children with long-term CVCs. METHODS: A
      retrospective review of children who had a long-term CVC in Seoul National
      University Children's Hospital between 2011 and 2015 was performed. Data on
      patient demographics, the isolated pathogens and the status of CVC placement were
      collected. Clinical variables were compared between subjects with and without
      CLABSIs to determine the risk factors for CLABSIs. RESULTS: A total of 629 CVCs
      were inserted in 499 children during the 5-year period. The median age at
      insertion was 6.0 years (14 days-17.9 years), and hemato-oncologic disease was
      the most common underlying condition (n = 497, 79.0%). A total of 235 CLABSI
      episodes occurred in 155 children, with a rate of 0.93 per 1,000 catheter days.
      The most common pathogens were Klebsiella pneumoniae (n = 64, 27.2%), coagulase
      negative staphylococci (n = 40, 17.0%) and Staphylococcus aureus (n = 28, 12.0%).
      In the univariate analysis, the gender, underlying disease, catheter
      characteristics and insertion technique did not increase the risk for CLABSI. In
      both the univariate and logistic regression analyses, patients with prior BSIs
      (odds ratio 1.66; 95% confidence interval: 1.090-2.531; P = 0.018) were more
      likely to have a CLABSI. CONCLUSIONS: CLABSI prevention is of particular concern
      for children with a prior BSI. Furthermore, the antimicrobial resistance of major
      pathogens should be monitored to enable the empiric selection of appropriate
      antibiotics in patients with long-term CVCs.

PMID- 29194166
TI  - Gun Violence-Make It Stop.

PMID- 29194167
TI  - Critical-Care Nurses' Pain Experiences and the Prognostic Factors.
AB  - OBJECTIVE: The objective of this study was to determine the emergence of pain in
      critical-care nurses and the prognostic risk factors. DESIGN: This study is a
      cross-sectional descriptive research. SETTING AND SUBJECTS: This study was
      conducted with the participation of 111 critical-care nurses in Zonguldak
      province, Turkey. INTERVENTIONS: The data were collected using a survey form and
      the Cornell Musculoskeletal Discomfort Questionnaire between August and November
      2015. The data were evaluated using frequency, average, Pearson correlation
      analysis, chi, logistic regression, and odds ratio tests. RESULTS: The critical
      care nurses were found to experience pain mostly in their lower backs (88.3%),
      upper backs (77.5%), right (76.6%) and left (78.4%) feet, necks (73.9%), and most
      infrequently in the right (28.8%) and left (28.8%) lower arms. Changing bed
      linens while the patient remained in bed and lifting, pulling, or pushing heavy
      materials caused those nurses who felt despondent and tired to feel significant
      pain in the shoulder, neck, upper arm, wrist, and knee (P < .05). CONCLUSIONS:
      These results were significant for placing emphasis on maintaining body mechanics
      while caring for patients, providing appropriate environmental conditions, and
      ensuring ergonomics to preserve the health of critical-care nurses who work in
      hospitals.

PMID- 29194169
TI  - Quality of Life of Adult Survivors After Extra Corporeal Membrane Oxygenation
      (ECMO): A Quantitative Study.
AB  - INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) is a technique used in
      the treatment of patients with severe respiratory failure. A lot of studies in
      the literature investigated the survival rate of patients treated with ECMO, but
      few are those that assess the long-term outcomes and the quality of life (QoL) of
      survivors. MATERIALS AND METHODS: A retrospective observational study with
      prospective QoL assessment through administration of the questionnaire EuroQol-5
      Dimension was conducted in acute respiratory distress syndrome patients who h ad
      ECMO as a rescue therapy for reversible refractory hypoxemia from January 2013
      until December 2015 in an Italian referral ECMO center. RESULTS: Forty patients
      were enrolled, but the telephone interview was possible only in 17. The
      interviewed patients presented a reduction in QoL in the items concerning pain
      (59%), followed by problems regarding mobility (47%) and anxiety (47%). The
      patients' perceived QoL, showed in a 0 to100 scale (0 being the worst, 100 being
      the best value), is of 75% (interquartile range, 70-80). DISCUSSION: The problems
      found are in agreement with the literature about this particular type of
      patients. CONCLUSION: Most ECMO patients have good physical and social
      functioning after hospital discharge.

PMID- 29194170
TI  - Collaborating With Hospital Chaplains to Meet the Spiritual Needs of Critical
      Care Patients.
AB  - There are many opportunities for critical-care nurses to collaborate with
      chaplains in an effort to provide spiritual care for patients and their families.
      By recognizing the educational requirements as well as the unique roles of board
      certified chaplains (BCCs), the critical-care nurse will view them as respected
      members of the health care team. This collaboration positively impacts the work
      environment and creates a holistic space for healing for patients, as well as the
      health care team. As nurses, we must educate and inform novice nurses about the
      important role of BCCs on the interdisciplinary health care team. Critical-care
      nurses need to incorporate the BCCs' contributions into the patient plan of care
      during bedside report in a way that helps the nurse understand the connection
      between the patient's spiritual health and his/her experience as a patient.

PMID- 29194171
TI  - Improving the Accuracy of Delirium Assessments in Neuroscience Patients: Scaling
      a Quality Improvement Program to Improve Nurses' Skill, Compliance, and Accuracy
      in the Use of the Confusion Assessment Method in the Intensive Care Unit Tool.
AB  - BACKGROUND: Delirium affects up to 80% of critically ill patients; however, many
      cases of delirium go unrecognized because of inaccurate assessments. The
      effectiveness of interventions to improve assessment accuracy among the general
      population has been established, but assessments among neuroscience patients are
      uniquely complicated due to the presence of structural neurologic changes.
      OBJECTIVES: The purposes of this quality improvement project were to improve the
      accuracy of nurse's delirium assessments among neuroscience patients and to
      determine the comparative effectiveness of the intervention between medical and
      neuroscience patients. METHODS: A multifaceted nurse-led intervention was
      implemented, and a retrospective analysis of preintervention and postintervention
      data on assessment accuracy was completed. Results were stratified by population,
      level of sedation, and level of care. Differences were analyzed using Fisher
      exact test. RESULTS: Data from 1052 delirium assessments were analyzed and
      demonstrated improvement in assessment accuracy from 56.82% to 95.07% among all
      patients and from 29.79% to 92.98% among sedate or agitated patients. Although
      baseline accuracy was significantly lower among neuroscience patients versus
      medical intensive care unit patients, no significant differences in
      postintervention accuracy were noted between groups. CONCLUSION: Results from
      this project demonstrate the effectiveness of the nurse-led intervention among
      neuroscience patients. Future research is needed to explore the effectiveness of
      this nurse-led intervention across other institutions and to describe the
      effectiveness of new interventions to improve outcomes at the patient and
      organizational levels.

PMID- 29194173
TI  - Unit-Level Changes in Central Line-Associated Bloodstream Infection Before and
      After Implementation of the Affordable Care Act and Mandatory Reporting
      Legislation.
AB  - BACKGROUND: Central line-associated bloodstream infection (CLABSI) prevention
      efforts have increased over the past decade because of implications of the
      Affordable Care Act and mandatory reporting laws. These legislative measures
      allow for reduced reimbursement to hospitals with high level of CLABSIs and other
      health care-associated infections. OBJECTIVE: The aim of this study was to
      explore the impact of legislation and mandatory reporting on CLABSI rates and
      reporting. METHODS: The study team performed a retrospective review of medical
      intensive care unit patients in January 2008, 2012, and 2015 to examine changes
      in CLABSI reporting by 2 methods (International Classification of Diseases [ICD]
      by providers and Centers for Disease Control by infection prevention [IP]), as
      well as changes in central line use over time. Data were summarized and compared.
      Percent agreement and kappa statistics were calculated for ICD- and IP-coded
      CLABSIs. RESULTS: Among 465 intensive care unit patients, most were white
      (89.9%), males (52.0%), aged 58.7 +/- 17.1 years. Only 3 new CLABSIs were
      reported during the study period: 2 by ICD and IP in 2008, 1 by ICD in 2012, and
      0 by either method in 2015. The percent agreement (99.6%) and kappa (0.799)
      represent excellent agreement. Central line usage was similar for each time
      period. DISCUSSION: The number of CLABSIs decreased over time; however, the
      findings were limited, and a larger sample over a longer period is needed to draw
      conclusions about the influence of legislative changes. One discrepancy was
      observed between the 2 reporting methods, which is consistent with other studies.
      More research is needed to understand the complexity of provider coding practices
      and changes in central line use (eg, duration, type, location) over time.

PMID- 29194174
TI  - The Effects of Endotracheal Suctioning in the Pediatric Population: An
      Integrative Review.
AB  - BACKGROUND: Critically ill pediatric patients with endotracheal tubes routinely
      receive endotracheal tube suctioning to clear secretions and ensure tube patency.
      This common practice can result in adverse effects. OBJECTIVES: The aim of this
      study was to evaluate the research literature on the stressors of endotracheal
      suctioning and consequent effect on the pediatric patient. METHODS: An
      integrative review was conducted using the Whittemore and Knafl modified
      framework for integrative reviews, and article selection was guided by the
      Preferred Reporting Items for Systematic Reviews and Meta-analyses flow diagram.
      A literature search was conducted via PubMed, the Cumulative Index to Nursing and
      Allied Health Literature, and Scopus. Selected articles were evaluated to present
      the current evidence on the stressors of endotracheal suctioning in the pediatric
      population. RESULTS: This review includes 14 articles, with a total of 849
      patients, ranging in age from premature neonates to 17 years of age. The
      available literature aligned into 3 categories: neurovascular effects,
      respiratory systems effects, and pain related to endotracheal tube suctioning.
      Pain was the most prevalent category, with half of the studies using endotracheal
      suctioning as a painful procedure to validate pain assessment tools rather than
      examining the effect of suctioning. A majority of the studies (67%) were
      conducted in the premature neonate population. Children with congenital cardiac
      or pulmonary defects, genetic syndromes, or neurological injuries were frequently
      excluded. CONCLUSIONS: Literature regarding the effects of endotracheal
      suctioning in children is limited. There are many extrapersonal, interpersonal,
      and intrapersonal stressors associated with endotracheal suctioning that merit
      future research.

PMID- 29194177
TI  - Efficacy of a Micro-Prompting Technology in Reducing Support Needed by People
      With Severe Acquired Brain Injury in Activities of Daily Living: A Randomized
      Control Trial.
AB  - OBJECTIVE: To evaluate the effectiveness of an automated interactive prompting
      technology in supporting the morning routine of persons with acquired brain
      injury. The morning routine included maintaining personal hygiene and dressing.
      SETTING: An inpatient neurorehabilitation hospital. PARTICIPANTS: Persons with
      acquired brain injury who required prompting when following their morning routine
      (n = 24), but were not limited by physical disability or dysphasia, took part in
      the study. Participants (67% with traumatic brain injury) had impairment on
      indices of memory and executive function. DESIGN: A randomized control trial
      evaluated the effect of an automated interactive micro-prompting device on the
      number of prompts by trained staff required for successful completion of the
      morning routine. MAIN MEASURES: Study-specific checklists assessed sequence
      performance, errors, and verbal prompts required over baseline, rehabilitation as
      usual, intervention, and return to baseline conditions. RESULTS: The intervention
      significantly reduced the support required to complete the task compared with
      usual rehabilitation. CONCLUSIONS: Micro-prompting technology is an effective
      assistive technology for cognition, which reduces support needs in people with
      significant cognitive impairments.

PMID- 29194176
TI  - Racial Disparities in Outpatient Mental Health Service Use Among Children
      Hospitalized for Traumatic Brain Injury.
AB  - OBJECTIVE: To examine racial differences in mental health service utilization
      after hospitalization for traumatic brain injury (TBI) among children with
      Medicaid insurance. DESIGN AND MAIN MEASURES: Retrospective analysis of the
      MarketScan Multi-State Medicaid database from 2007 to 2012 was performed.
      Outpatient mental health service utilization (psychiatric and psychological
      individual and group services) was compared at TBI hospitalization, from
      discharge to 3 months and from 4 to 12 months after discharge, between children
      of non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and "Other"
      racial groups. Multivariable mixed-effects Poisson regression models with robust
      standard errors were utilized. RESULTS: A total of 5674 children (aged <21 years)
      were included in the study. There were no differences by race/ethnicity in mental
      health service utilization during hospitalization. At 3 months postdischarge, NHB
      children and children in the "Other" racial category were significantly less
      likely to receive outpatient mental health services than NHW children (NHB
      relative risk [RR] = 0.84; 95% confidence interval [CI], 0.72-0.98; Other RR =
      0.72; 95% CI, 0.57-0.90). At 12 months, all racial minority children were
      significantly less likely to receive outpatient mental health services than NHW
      children (NHB RR = 0.84; 95% CI, 0.75-0.94; Hispanic RR = 0.72; 95% CI, 0.55
      0.94; Other RR = 0.71; 95% CI, 0.60-0.84). CONCLUSIONS: Racial disparities in
      utilization of outpatient mental health services exist for minority children
      hospitalized for TBI and insured by Medicaid. Future research should focus on
      improving transitions of care from inpatient to outpatient services for these
      children.

PMID- 29194178
TI  - Relationship Between Neurocognitive Function and Self-Discrepancy After Severe
      Traumatic Brain Injury.
AB  - OBJECTIVE: Individuals with traumatic brain injury (TBI) often make unfavorable
      comparisons between their preinjury and postinjury selves. Although it is known
      that negative "self-discrepancy" is related to poorer emotional adjustment, the
      impact of neurocognitive function on self-discrepancy is unclear. This study
      aimed to investigate the relationship between current neurocognitive function
      (attention, memory, executive function, and self-awareness) and self-discrepancy
      after severe TBI. DESIGN: Fifty-four adults with severe TBI were recruited from
      outpatient and community rehabilitation services and completed measures of self
      discrepancy (Head Injury Semantic Differential Scale-III) and self-awareness
      (Awareness Questionnaire) and a battery of standardized tests of attention,
      memory, and executive functions. RESULTS: More negative self-discrepancy was
      significantly associated with greater self-awareness (r = -0.40, P < .001) and
      better performance on tests of immediate memory (r = -0.43, P < .01), working
      memory (r = -0.35, P < .05), and verbal fluency (r = -0.34, P < .05). Self
      awareness was the only neurocognitive factor significantly and uniquely related
      to self-discrepancy, accounting for 8.6% of the variance (P < .05). Furthermore,
      self-awareness was found to partially mediate the relationship between immediate
      memory and self-discrepancy. CONCLUSION: Better neurocognitive function is
      related to more negative self-discrepancy. These findings improve understanding
      of the process of identity reconstruction following TBI.

PMID- 29194179
TI  - Correspondence of the Boston Assessment of Traumatic Brain Injury-Lifetime and
      the VA Comprehensive TBI Evaluation.
AB  - OBJECTIVE: To compare the diagnosis of positive versus negative for mild
      traumatic brain injury (mTBI) using the Boston Assessment of TBI-Lifetime (BAT
      L), a validated forensic clinical interview used to identify TBI in research, to
      the diagnosis of mTBI in the clinical polytrauma service using the Comprehensive
      TBI Evaluation (CTBIE). PARTICIPANTS: Operation Enduring Freedom/Operation Iraqi
      Freedom/Operation New Dawn Veterans who were enrolled in the Translational
      Research Center for TBI and Stress Disorders longitudinal cohort study and
      received a CTBIE at a Veterans Health Administration healthcare facility (n =
      104). MAIN MEASURES: The BAT-L, CTBIE, and Neurobehavioral Symptom Inventory.
      RESULTS: There was poor correspondence between the BAT-L and CTBIE mTBI diagnoses
      (kappa = 0.283). The CTBIE showed moderate sensitivity but poor specificity
      relative to the BAT-L. The agreement did not improve after removing individuals
      who had failed symptom validity measures, as assessed by the Validity-10 scale of
      the Neurobehavioral Symptom Inventory. CONCLUSIONS: This lack of correspondence
      highlights the difficulties in diagnosing mTBI in Veterans using retrospective
      self-report. Future work is needed to establish a reliable and valid method for
      identifying military mTBI both for the care of our Veterans and for appropriate
      distribution of benefits.

PMID- 29194180
TI  - Agitated Behavior and Activities of Daily Living Retraining During Posttraumatic
      Amnesia.
AB  - BACKGROUND: Patients in posttraumatic amnesia (PTA) may receive limited
      rehabilitation due to the risk of overstimulation and agitation. This assumption
      has not been tested. OBJECTIVE: To examine the relationship between agitated
      behavior and participation in therapy for retraining of activities of daily
      living (ADL) while in PTA. SETTING: Inpatient rehabilitation center.
      PARTICIPANTS: A total of 104 participants with severe traumatic brain injury,
      admitted to rehabilitation, in PTA of more than 7 days. INTERVENTION: ADL
      retraining during PTA followed errorless and procedural learning principles.
      DESIGN: Group comparison and regression modeling of patient agitation data from a
      randomized controlled trial comparing ADL retraining in PTA (treatment) versus no
      ADL retraining in PTA (treatment as usual, TAU). OUTCOME MEASURES: Agitation
      using the Agitated Behavior Scale. Therapy participation measured in minutes and
      missed sessions. RESULTS: There were no group differences in agitated behavior
      (average scores, peak scores, or number of clinically agitated days) between the
      treatment and TAU groups. For treated patients, there was no significant
      relationship between agitation and therapy participation (therapy minutes or
      missed ADL treatment sessions). CONCLUSIONS: This study demonstrated that
      agitation is not increased by delivery of structured ADL retraining during PTA
      and agitation did not limit therapy participation. This supports the
      consideration of active therapy during PTA.

PMID- 29194181
TI  - Feasibility of a Skills-Based Group Reintegration Workshop for OEF/OIF Veterans:
      STEP-Home.
AB  - OBJECTIVE: To evaluate the feasibility of a newly developed reintegration
      workshop for Operation Iraqi Freedom/Operation Enduring Freedom (OEF/OIF)
      Veterans that is based on an evidence-based rehabilitation program shown to be
      effective in treating mild traumatic brain injury-related symptoms in civilians.
      Underutilization and resistance to mental health treatment remain a significant
      problem for OEF/OIF Veterans. Innovative, integrative, transdiagnostic, and
      acceptable interventions are needed, particularly for this heterogeneous group.
      PARTICIPANTS: Eighty-four OEF/OIF/Operation New Dawn Veterans (74 male and 10
      female)-mean age = 35; standard deviation = 7.4. SETTING: VA Healthcare System.
      INTERVENTION: A 12-week, 2-hour/wk, group skills-based workshop with individual
      skill building to assist all OEF/OIF Veterans (with and without psychiatric
      and/or traumatic brain injury) in reintegration after military service. MAIN
      MEASURES: Primary outcomes were feasibility measures including treatment
      fidelity, acceptability, tolerability/adherence, and treatment-related skill
      acquisition. Secondary outcomes were interest and engagement in future treatment
      and reintegration status. RESULTS: Veterans' enrollment, adherence, and attrition
      data indicated that Short-Term Executive Plus adapted for Veteran civilian
      reintegration (STEP-Home) was acceptable and tolerable. Pre-/postintervention
      differences in attention, problem-solving, and emotional regulation skills
      demonstrated treatment-related skills acquisition. Secondary outcome data
      demonstrated Veterans who were hesitant to participate in mental health
      treatments before enrollment were more open to treatment engagement after STEP
      Home, and reintegration status improved. CONCLUSIONS: This study demonstrated
      that the STEP-Home workshop is feasible in OEF/OIF Veterans and changes in
      treatment-related skill acquisition and reintegration status were observed. STEP
      Home has potential to facilitate readjustment and serves as a gateway to
      additional, critically needed Veterans Administration services.

PMID- 29194182
TI  - Effect of Postactivation Potentiation Induced by Elastic Resistance on Kinematics
      and Performance in a Roundhouse Kick of Trained Martial Arts Practitioners.
AB  - Aandahl, HS, Von Heimburg, E, and Van den Tillaar, R. Effect of postactivation
      potentiation induced by elastic resistance on kinematics and performance in a
      roundhouse kick of trained martial arts practitioners. J Strength Cond Res 32(4):
      990-996, 2018-The aim of this study was to examine whether kicking with elastic
      resistance during warm-up could initiate postactivation potentiation (PAP), and
      thereby positively influence kinematics and performance on subsequent explosive
      roundhouse kicking. Five women and 11 men (n = 16) with a background in
      kickboxing (n = 10) or taekwondo (n = 6) performed 2 warm-up strategies with 3
      subsequent test kicks 5-8 minutes after a PAP-inducing exercise. Kicking
      performance, defined as roundhouse kicking velocity with the foot, was measured
      using 3D motion capture (500 Hz) with a 15 marker lower-body 3D model. In
      addition, electromyography of the prime movers-vastus lateralis, vastus medialis,
      and rectus femoris muscles-was measured to confirm the presence of PAP. Kicking
      velocity of the foot increased by 3.3% after performing a warming-up strategy
      including kicking with elastic resistance (p = 0.009, eta = 0.32). Increases were
      also recorded in muscle activity in vastus medialis (35.2%, p = 0.05, eta = 0.18)
      and rectus femoris (43.9%, p = 0.04, eta = 0.20). These findings indicate that
      performing a warm-up strategy including kicking with elastic resistance can have
      a positive effect on kicking performance in a roundhouse kick.

PMID- 29194184
TI  - Biomechanical Comparison of Loaded Countermovement Jumps Performed on Land and in
      Water.
AB  - Researchers have observed physical improvements following the completion of
      aquatic-based jump training. However, there is a lack of research on the
      biomechanical specificity of aquatic-based movement. Therefore, the purpose of
      this investigation was to evaluate the kinetics and kinematics of loaded
      countermovement jumps performed in water versus land. Twenty young males and
      twenty-four NCAA division I women's soccer and gymnastics athletes were asked to
      perform unloaded and loaded countermovement jumps on land and in chest-deep water
      immersion. A tri-axial force platform and two dimensional videography produced
      various kinetic and kinematic measures of jump performance. Peak and mean
      mechanical power outputs (W) were 88% (8919+/-3744W vs. 4734+/-1418W; p<0.001)
      and 81% (3640+/-1807W vs. 2011+/-736W; p<0.001) greater for jumps performed in
      water versus land. Peak dorsiflexion velocity was 688% faster (44+/-39 degrees /s
      vs. 5.6+/-5.4 degrees /s; p<0.001) for jumps performed in water and tended to
      model similarly with measures of mechanical power and amortization rate.
      Bodyweight normalized peak and mean mechanical power outputs decreased by 23.6+/
      2.7% and 23.8+/-1.9% when load was added in the water. The addition of load on
      land was associated with an 8.7+/-2.3% and 10.5+/-4.4% decrease in bodyweight
      normalized peak and mean mechanical power. Results suggest that the aquatic
      environment alters movement primarily at amortization and may provide a unique
      training stimulus. Also, it can be concluded that fluid resistance and buoyancy
      combine to influence the mechanics of jumping movements performed in the water.

PMID- 29194183
TI  - Hyperactivity of the Sympatho-Adrenomedullary System Without Any Modification of
      the Hypothalamic-Pituitary-Adrenal Axis After Food Restriction Among High-Level
      Weightlifters.
AB  - Durguerian, A, Filaire, E, Drogou, C, Sauvet, F, Bougard, C, and Chennaoui, M.
      Hyperactivity of the sympatho-adrenomedullary system without any modification of
      the hypothalamic-pituitary-adrenal axis after food restriction among high-level
      weightlifters. J Strength Cond Res 32(6): 1643-1655, 2018-We examined the effects
      of 6 days of food restriction on salivary alpha-amylase (sAA), cortisol and
      dehydroepiandrostenedione (DHEA) awakening responses, psychological parameters
      and performance among 11 international weightlifters. Assessments were made at
      baseline (T1) and 6 days after a normal period of training while maintaining body
      weight (T2). Then, participants were assigned to 2 groups depending on whether
      they lost (Diet group) or maintained (Control group) their body mass.
      Anthropometric, psychological, physical, and physiological assessments were also
      realized 6 days (T3) after the restricted dietary period for the Diet group. Food
      restriction (T3) induced a significant rise of sAA awakening response (364.6%, p
      <= 0.05), whereas no significant variations were observed among the hypothalamic
      pituitary-adrenal axis (cortisol and DHEA). Significant alterations of the
      general Recovery Score and General stress Score, evaluated through the Recovery
      Stress Questionnaire for athletes, were noted after food restriction.
      Weightlifting performance, evaluated during a simulated weightlifting
      competition, was maintained after the 6-day food restriction; we even noted an
      increased weightlifting performance related to body mass (Sinclair coefficient).
      Our findings support the hypothesis that food restriction induces a challenging
      situation to the organism, resulting in an asymmetry between the 2 stress systems
      activation. These results reinforce the necessity to cautiously plan and monitor
      the weight regulation process before competition to avoid potential negative
      outcomes on psychophysiological parameters. In this regard, the psychobiological
      approach, especially the awakening responses, seems a useful tool.

PMID- 29194185
TI  - Does Maturity Status Affect The Relationship Between Anaerobic Speed Reserve And
      Multiple Sprints Sets Performance in Young Soccer Players?
AB  - The purpose of this study is to examine the relationship between repeated-sprint
      sets (RSS) performance indices and anaerobic speed reserve (ASR) in young soccer
      players of different maturity status. One hundred and seventy nine young male
      soccer players (11.1 to 17.8 years) classified as pre- (n=50), circum- (n=60), or
      post- (n=69) peak height velocity (PHV) performed multi-stage shuttle run test
      (MRST) to measure maximal aerobic speed (MAS), 30-m sprint with 10-m splits to
      estimate maximal anaerobic speed (MAnS), and RSS test. ASR was calculated as the
      difference between MAS and MAnS. The RSS indices, MAS, MAnS and ASR were
      significantly different in the three maturity groups (p< 0.001; ES =0.12-0.64).
      Correlations between RSS performance indices and ASR varied considerably
      depending on maturity status. Very large correlations between ASR and RSS indices
      expressed as sum sprint time (SST) and best sprint time (BST) were found for pre-
      and circum-PHV groups (r=-0.76, -0.79 and r=-0.82, -0.86, respectively). In the
      post-PHV group, ASR was moderately associated with both SST (r=-0.45) and BST (r=
      0.46). To sum up, these results highlighted that the ASR is more related to
      factors of RSS performance in pre- and circum-PHV male soccer players compared
      with post-PHV ones. These findings could help coaches and strength and
      conditioning professionals to better understand how the relationship between ASR
      and RSS evolve across the maturity and may be considered, therefore, useful in
      youth soccer selection/training process.

PMID- 29194186
TI  - The Impact of Different Cross-Training Modalities on Performance and Injury
      Related Variables in High School Cross Country Runners.
AB  - Paquette, MR, Peel, SA, Smith, RE, Temme, M, and Dwyer, JN. The impact of
      different cross-training modalities on performance and injury-related variables
      in high school cross country runners. J Strength Cond Res 32(6): 1745-1753, 2018
      There are many different types of aerobic cross-training modalities currently
      available. It is important to consider the effects that these different
      modalities have on running performance and injury risks. The purpose of this
      study was to compare movement quality, running economy (RE) and performance,
      injury-related biomechanical variables, and hip muscle strength before and after
      training with different cross-training modalities in high school runners. Thirty
      one high school male runners trained for 4 weeks in 1 of 3 cross-training
      modalities, in addition to a running-only (n = 9) group, for which training
      sessions replaced 2 easy runs per week: cycling (CYCLE; n = 6), indoor elliptical
      (n = 7), and outdoor elliptical bike (EBIKE; n = 9). Functional movement screen
      (FMS), RE, 3,000-m performance, hip kinematics, and hip muscle strength were
      assessed. Paired t-tests and Cohen's d effect sizes were used to assess mean
      differences for each variable before and after training within each group.
      Elliptical bike training was the only modality that improved FMS scores (d =
      1.36) and RE before and after training (d = 0.48). All groups showed improvements
      in 3,000-m performance, but large effects were found only for the CYCLE (d =
      1.50) and EBIKE (d = 1.41) groups. Running-only (d = 1.25), CYCLE (d = 1.17), and
      EBIKE (d = 0.82) groups showed improvements in maximal hip extensor strength.
      Outdoor cycling and EBIKE cross-training may be the most effective cross-training
      modalities to incorporate in early season training to improve running performance
      in high school runners.

PMID- 29194187
TI  - The prevalence of coronary artery disease in patients with liver cirrhosis: a
      meta-analysis.

PMID- 29194189
TI  - Ovarian Yolk Sac Tumors; Does Age Matter?
AB  - BACKGROUND: Whereas among pediatric oncologists, ovarian yolk sac tumor (O-YST)
      is considered a chemosensitive tumor, it is often cited as an adverse prognostic
      factor in adult women with ovarian germ cell tumors. METHODS: The Malignant Germ
      Cell International Consortium data set included 6 pediatric clinical trials
      (United States, United Kingdom, and France) and 2 adult gynecology clinical
      trials (United States). Any patient with an O-YST that was International
      Federation of Gynecology and Obstetrics stage IC or higher and treated with a
      platinum-based chemotherapy was eligible. Age was modeled as a continuous and a
      categorical variable (children, 0-10 years; adolescents, 11-17 years; and adults,
      >=18 years). In addition, analyses to establish the optimal cut point for age
      were conducted. Tumors were coded as pure YST (YST +/- teratoma), mixed YST (YST
      + other malignant germ cell component), or putative YST ("mixed" germ cell tumor
      + alpha-fetoprotein >1000 ng/mL). Histology, stage (II/III vs IV), preoperative
      alpha-fetoprotein levels (<1000; 1000-10,000, or >10,000 ng/mL), and
      chemotherapeutic regimen (carboplatin vs cisplatin) were analyzed as covariates.
      RESULTS: Two hundred fifty-one patients (median age, 13 years; range, 0-38 years)
      were identified (78 children, 139 adolescents, and 34 adults). Histology was
      pure, mixed, and putative in 129, 56, and 66 cases, respectively. Twenty-six
      patients had stage IV disease, similarly distributed in the 3 age groups. Median
      follow-up was 5.8 years. The overall 5-year event-free survival and overall
      survival was 91% (95% confidence interval, 87%-94%) and 96% (92%-98%),
      respectively. Age did not affect risk of event or death, modeled either as a
      categorical or continuous variable. Analysis failed to identify an age cut point
      that affected risk. None of the other covariates investigated had a prognostic
      impact on event-free survival or overall survival. CONCLUSIONS: Ovarian yolk sac
      tumors have an excellent outcome across all age-groups. Age has no apparent
      impact on the probability of event or death, allowing pediatric and gynecologic
      oncologists to enroll patients onto joint pediatric and adult trials.

PMID- 29194190
TI  - An Evaluation of Frozen Section and Lymph Node Dissection Results for Mucinous
      Ovarian Tumors.
AB  - OBJECTIVES: Intraoperative frozen section has greater than 90% accuracy for
      ovarian tumors; however, mucinous histology has been shown to be associated with
      increased frozen section inaccuracy. Recent data demonstrate that primary ovarian
      mucinous carcinomas have no lymph node involvement, even when extraovarian
      disease is present, and therefore may not require lymph node dissection. Our
      primary objective is to evaluate the accuracy of identifying mucinous histology
      on frozen section. METHODS/MATERIALS: A cross-sectional review of mucinous
      ovarian tumors in surgical patients at one institution from 2006 to 2016 was
      performed. Cases reporting a mucinous ovarian tumor on frozen section or final
      pathology were identified. Frozen section results were compared with final
      diagnosis to calculate concordance rates. Analyses with chi and t tests were
      performed to identify variables associated with pathology discordance. RESULTS: A
      total of 126 mucinous ovarian tumors were identified. Of these, 106 were reported
      as mucinous on frozen section and 103 (97.2%) were concordant on final pathology.
      Discordant cases included 2 serous and 1 clear cell tumor. Among the 103 mucinous
      tumors, classification as malignant, borderline, or benign was concordant in 74
      (71.8%) of 103 cases, whereas 22 (21.4%) of 103 were discordant and 7 (6.8%) were
      deferred to final pathology. Lymph node dissection was performed in 33 cases; the
      only case with lymph node metastasis was a gastrointestinal mucinous
      adenocarcinoma. Discordance between frozen section and final pathology was
      associated with larger tumor size and diagnosis other than benign: discordant
      cases had a mean tumor size of 21.7 cm compared with 14.4 cm for concordant cases
      (P < 0.001), and 93.5% of discordant cases were borderline or malignant, compared
      with 30.5% of concordant cases (P < 0.001). CONCLUSIONS: Intraoperative
      identification of mucinous histology by frozen section is reliable with a
      concordance rate to final pathology of 97.2%. No lymph node metastases were
      present in any malignant or borderline primary ovarian cases.

PMID- 29194191
TI  - BRCA Mutation Status Is Not Associated With Increased Hematologic Toxicity Among
      Patients Undergoing Platinum-Based Chemotherapy for Ovarian Cancer.
AB  - OBJECTIVE: Women with an inherited BRCA1 or BRCA2 mutation may have an impaired
      ability to repair chemotherapy-induced damage as a result of a state of
      haploinsufficiency and may experience greater treatment-related toxicity. The
      objective of this study was to compare the hematologic adverse effect profiles
      associated with platinum-based chemotherapy in ovarian cancer patients with and
      without germline BRCA mutations. METHODS: We conducted a retrospective analysis
      of patients treated for high-grade serous ovarian cancer at Princess Margaret
      Cancer Center, Toronto, Ontario between January 2000 and December 2015. We
      included only women with known BRCA mutation status and who received first-line
      platinum-based chemotherapy. We compared 3 primary measures of myelosuppression
      (ie, hemoglobin levels, platelet counts, and neutrophil counts) before each cycle
      of chemotherapy in patients with and without a BRCA mutation. RESULTS: We
      included 130 BRCA mutation carriers and 302 noncarriers who met the eligibility
      criteria. There were no significant differences in baseline hemoglobin levels,
      neutrophil counts, or platelet counts between the groups (P >= 0.31). We found no
      significant difference in 3 measures of hematologic toxicity (ie, neutropenia,
      anemia, or thrombocytopenia) based on BRCA mutation status across all
      chemotherapy cycles (P >= 0.06). Although BRCA mutation carriers were more likely
      to experience an absolute neutrophil count below 1.0 * 10/L than noncarriers (P =
      0.02), this did not translate to an increased frequency of dose reduction or dose
      delay. DISCUSSION: Among women with ovarian cancer, hematologic toxicity does not
      appear to be more frequent in BRCA mutation carriers than in noncarriers. This is
      reassuring for clinicians treating ovarian cancer patients with respect to dosing
      regimens. These findings do not support the hypothesis that a haploinsufficiency
      phenotype exists with respect to the repair of chemotherapy-induced double-strand
      DNA breaks in this high-risk population.

PMID- 29194192
TI  - Sentinel Node Biopsy in Endometrial Cancer With Dual Cervical and Fundal
      Indocyanine Green Injection.
AB  - PURPOSE: The aim of this study was describe a novel sentinel lymph node (SLN)
      tracer injection procedure featuring dual cervical and fundal indocyanine green
      (ICG) injection for endometrial cancer and results of SLN biopsy. METHODS:
      Between June 26, 2014 and October 31, 2016, 111 patients underwent laparoscopic
      surgery for endometrial cancer at our institution. In all cases, we performed SLN
      biopsy with dual cervical and fundal ICG injection. All SLNs were processed with
      an ultrastaging technique. A total of 69 patients also underwent total pelvic and
      paraaortic lymphadenectomy. RESULTS: The detection rates were as follows: 92.79%
      (103/111) overall for SLNs; 89.19% (99/111) overall for pelvic SLNs; 61.26%
      (68/111) for bilateral SLNs; 59.46% (66/111) for paraaortic SLNs, and 4% (4/111)
      for isolated paraaortic SLNs. We found macroscopic lymph node metastasis in 11
      patients (9.9%) and microdisease in lymph nodes in another 10 patients, raising
      the overall rate of lymph node involvement to 18.92%. There was 1 false-negative
      (negative SLN biopsy but positive aortic lymphadenectomy) and another positive
      case in 1 undetected SLN. The sensitivity of detection was 94.44%, specificity
      100%, negative predictive value 97.83%, and negative likelihood ratio 0.06 for
      intermediate and high-risk endometrial cancer groups. CONCLUSIONS: The SLN biopsy
      with both cervical and fundal ICG injection offers good overall detection rates
      and improved mapping of the aortic area. The SLN ultrastaging increases the
      number of nodes considered positive.

PMID- 29194193
TI  - Clinical Predictors of Recurrence and Prognostic Value of Lymph Node Involvement
      in the Serous Borderline Ovarian Tumor.
AB  - AIM: This study was aimed to evaluate the risk factors of recurrence and the
      value of nodal involvement in patients with serous borderline ovarian tumors
      (SBOT). METHODS: Two hundred twenty-five patients who underwent surgery and were
      diagnosed with SBOT were retrospectively studied. Univariate and multivariate
      analyses were used to assess the risk factors for recurrence. Patients' clinical
      pathologic characteristics were compared between the patients who presented lymph
      node involvement and those who did not. The significant values of lymph condition
      influencing 5-year disease-free survival were also evaluated by statistical
      analysis. RESULTS: Both univariate and multivariate analyses showed that risk
      factors for recurrence were micropapillary (P = 0.021), fertility-preserving
      surgery (P = 0.014), and laparoscopic approach (P = 0.009). Of these 112 patients
      on whom lymphadenectomy was performed, 17 cases showed lymph node positive,
      whereas the remaining 95 patients did not. Significant differences in terms of
      lymph node numbers (P < 0.0001), invasive implant (P = 0.022), and International
      Federation of Gynecology and Obstetrics staging (P < 0.0001) were observed
      between the 2 groups of lymphatic node involved or not. Kaplan-Meier curves of 5
      year disease-free survival revealed that there were no significant differences
      either between groups of lymphatic node involved or not (P = 0.778) and groups of
      removed nodes whether more than 10 or not (P = 0.549). CONCLUSIONS:
      Micropapillary, fertility-preserving, and laparoscopic approach were factors
      significantly affecting the recurrence of SBOT by both univariate and
      multivariate analysis. Lymph node metastasis did not seem to be correlated to a
      worse prognosis of SBOT.

PMID- 29194194
TI  - Feasibility of Sentinel Node Mapping in Ovarian Tumors: What Is the Evidence?

PMID- 29194195
TI  - Gene Expression Signature-Based Prediction of Lymph Node Metastasis in Patients
      With Endometrioid Endometrial Cancer.
AB  - OBJECTIVE: This study aimed to develop a prediction model for lymph node
      metastasis using a gene expression signature in patients with endometrioid-type
      endometrial cancer. METHODS: Newly diagnosed endometrioid-type endometrial cancer
      cases in which the patients had undergone lymphadenectomy during a surgical
      staging procedure were identified from a national dataset (N = 330). Clinical and
      pathologic data were extracted from patient medical records, and gene expression
      datasets of their tumors were used to create a 12-gene predictive model for lymph
      node metastasis. We used principal components analysis on a training set (n =
      110) to develop multivariate logistic models to predict low-risk patients having
      a probability of lymph node metastasis of less than 4%. The model with the
      highest prediction performance was selected for an evaluation set (n = 112),
      which, in turn, was validated in an independent validation set (n = 108).
      RESULTS: The model applied to the evaluation set showed 100% sensitivity (90%
      confidence interval [CI], 74%-100%) and 42% specificity (90% CI, 34%-51%), which
      resulted in 100% negative predictive value (90% CI, 89%-100%). In the validation
      set, we confirmed that the model consistently showed 100% sensitivity (90% CI,
      88%-100%), 42% specificity (90% CI, 32%-50%), and 100% negative predictive value
      (90% CI, 88%-100%). CONCLUSIONS: Our 12-gene signature model is a useful tool for
      the identification of patients with endometrioid-type endometrial cancer at low
      risk of lymph node metastasis, particularly given that it can be used to analyze
      histologic tissue before surgery and used to tailor surgical options.

PMID- 29194196
TI  - Use of Optical Coherence Tomography by Nonexpert Personnel as a Screening
      Approach for Glaucoma.
AB  - PURPOSE: This pilot study was conducted to assess optical coherence tomography
      (OCT) as a screening tool for glaucoma when used by nonexpert personnel. METHODS:
      This prospective case-control study included 54 patients with open-angle glaucoma
      and 54 age-matched comparison individuals. Optovue iVue SD-OCT imaging was
      performed by nonprofessional photographers on undilated patients. The
      sensitivity, specificity, negative predictive value, and positive predictive
      value of iVue scan parameters for detecting open-angle glaucoma were evaluated.
      RESULTS: The iVue cup to disc vertical ratio had a sensitivity of 0.96 [95%
      confidence interval (CI), 0.90-1.00] at 90% specificity and was strongly
      correlated with both the Cirrus HD-OCT cup to disc vertical ratio (Pearson
      coefficient=0.84) and the cup to disc ratio observed on dilated clinical
      examination by faculty ophthalmologists (Pearson coefficient=0.80). The retinal
      nerve fiber layer (RNFL) parameters performed robustly, but the ganglion cell
      complex parameters showed limited diagnostic value. The inferior quadrant
      thickness was among the best performing RNFL parameters, with a sensitivity of
      0.87 (95% CI, 0.78-0.96) and a specificity of 0.88 (95% CI, 0.80-0.97) using the
      iVue normative database thresholds for abnormality. CONCLUSIONS: OCT imaging may
      be performed by nonprofessional photographers on undilated patients, and
      quantitative parameters derived from the resultant images, particularly the
      vertical cup to disc ratio and the RNFL inferior quadrant thickness, demonstrate
      sensitivities and specificities that may be adequately robust for glaucoma
      screening in the community setting.

PMID- 29194197
TI  - Diurnal Variation of Optical Coherence Tomography Measurements of Static and
      Dynamic Anterior Segment Parameters.
AB  - PURPOSE: To examine the diurnal variation of static and dynamic anterior segment
      parameters in young, healthy eyes by comparing anterior segment optical coherence
      tomography (AS-OCT) measurements obtained in the morning and evening and also in
      the light and dark. METHODS: Twenty-two subjects ranging from 19 to 47 years of
      age with no past ocular history were selected. Imaging was performed with the
      Tomey CASIA2 AS-OCT device in 2 fixed lighting environments, light and dark,
      between the hours of 08:30 to 10:00 and 17:30 to 19:00. Four AS-OCT images were
      analyzed per eye. Pupil diameter (PD), iris area (IA), iris curvature (IC),
      anterior chamber depth (ACD), lens vault (LV), anterior chamber width (ACW),
      anterior chamber area (ACA), angle opening distance (AOD), angle recess area
      (ARA), trabecular iris space area (TISA), and trabecular iris angle (TIA) were
      measured. RESULTS: Pupil diameter was similar between the AM and PM groups in the
      light (P=0.89) and dark (P=0.51). There was no significant difference between AM
      and PM measurement values for any of the static or dynamic parameters in the
      light (P>0.39) and dark (P>0.31). Intraclass correlation coefficients (ICC)
      demonstrated excellent agreement between AM and PM measurement values in the
      light (ICC>0.81) and dark (ICC>0.93). In addition, there was no significant
      difference between AM and PM angle opening distance at 500 um measurement values
      in the light (P>0.34) and dark (P>0.40) when each of 8 angle sectors was analyzed
      individually. CONCLUSIONS: No significant diurnal variation of static or dynamic
      anterior segment parameter measurements was detected in the light and dark.
      Diurnal variation of these parameters does not regularly occur in young, healthy
      eyes.

PMID- 29194198
TI  - Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular
      Hypertension: Pooled Phase 3 Study Findings.
AB  - PURPOSE: To compare the diurnal intraocular pressure (IOP)-lowering effect of
      latanoprostene bunod (LBN) 0.024% with timolol maleate 0.5% in subjects with open
      angle glaucoma (OAG) or ocular hypertension (OHT). PATIENTS AND METHODS: Pooled
      analysis of two phase 3, randomized, multicenter, double-masked, parallel-group,
      noninferiority trials (APOLLO and LUNAR), each with open-label safety extension
      phases. Adults with OAG or OHT were randomized 2:1 to double-masked treatment
      with LBN once daily (qd) or timolol twice daily (bid) for 3 months followed by
      open-label LBN treatment for 3 (LUNAR) or 9 (APOLLO) months. IOP was measured at
      8 AM, 12 PM, and 4 PM at week 2, week 6, and months 3, 6, 9, and 12. RESULTS: Of
      the 840 subjects randomized, 774 (LBN, n=523; timolol crossover to LBN, n=251)
      completed the efficacy phase, and 738 completed the safety extension phase. Mean
      IOP was significantly lower with LBN versus timolol at all 9 evaluation
      timepoints during the efficacy phase (P<0.001). A significantly greater
      proportion of LBN-treated subjects attained a mean IOP <=18 mm Hg and IOP
      reduction >=25% from baseline versus timolol-treated subjects (P<0.001). The IOP
      reduction with LBN was sustained through the safety phase; subjects crossed over
      from timolol to LBN experienced additional significant IOP lowering (P<=0.009).
      Both treatments were well tolerated, and there were no safety concerns with long
      term LBN treatment. CONCLUSIONS: In this pooled analysis of subjects with OAG and
      OHT, LBN 0.024% qd provided greater IOP-lowering compared with timolol 0.5% bid
      and maintained lowered IOP through 12 months. LBN demonstrated a safety profile
      comparable to that of prostaglandin analogs.

PMID- 29194199
TI  - Evaluation of a Trabecular Microbypass Stent With Cataract Extraction in Severe
      Primary Open-angle Glaucoma.
AB  - PURPOSE: To evaluate the safety and efficacy of a trabecular microbypass stent
      combined with cataract surgery in patients with severe open-angle glaucoma.
      PATIENTS: The series included 59 eyes with severe primary open-angle glaucoma and
      severe visual field loss as defined by American Academy of Ophthalmology
      preferred practice pattern criteria. MATERIALS AND METHODS: Retrospective case
      series. Patients were implanted with 1 trabecular microbypass stent with
      concomitant cataract surgery. Primary outcome measures were intraocular pressure
      (IOP) and number of glaucoma medications. Safety measures included postoperative
      IOP pressure spikes >=15 mm Hg or IOP<6 mm Hg at any time point, and the need for
      additional surgery. RESULTS: The mean preoperative IOP was 19.25+/-6.97 mm Hg.
      Postoperatively, the mean IOP was 14.38+/-3.63 mm Hg (P<0.01) at 12 months and
      14.92+/-3.86 mm Hg (P<0.01) at 24 months. The mean number of glaucoma medications
      was 2.27+/-1.06 preoperatively and 1.63+/-1.17 (P<0.01) at 24 months
      postoperative, indicating a 28% reduction in medication use. In total, 4 (7%)
      eyes required additional surgery. In total, 5 eyes (8%) experienced IOP spikes
      >=15 mm Hg, 14 (24%) eyes had IOP spikes >=10 mm Hg. Overall 55% of eyes had a
      20% IOP reduction after 24 months of surgery. Eyes with baseline IOP<=19 had a
      mean reduction of 2.24 mm Hg 36 months after surgery. CONCLUSIONS: Trabecular
      microbypass stent implantation during cataract surgery safely and effectively
      lowers IOP and medication use in patients with severe primary open-angle
      glaucoma.

PMID- 29194200
TI  - Evaluation of Angle Closure as a Risk Factor for Reduced Corneal Endothelial Cell
      Density: Comment.

PMID- 29194201
TI  - Evaluation of Long-term Anatomic Changes Following Canaloplasty With Anterior
      Segment Spectral-domain Optical Coherence Tomography and Ultrasound
      Biomicroscopy.
AB  - BACKGROUND: To analyze long-term structural changes in conjunctiva, sclera and
      Schlemm canal (SC) with anterior segment optical coherence tomography (AS-OCT)
      and ultrasound biomicroscopy (UBM) following uncomplicated canaloplasty.
      MATERIALS AND METHODS: Fifteen patients with planned canaloplasty and no
      intraoperative complications were included in this prospective study. AS-OCT
      images were acquired at 1, 3, 6 months and at a long-term time point (20+/-4.9
      mo) postsurgery. UBM images were acquired at 3, 6 months and long-term after
      canaloplasty. The surgical site was evaluated for the presence of SC,
      transscleral filtration, a scleral lake, and the visibility of intra-Schlemm
      sutures. The SC's height and width were measured at the 3 and 9 o'clock limbus
      position. RESULTS: Following canaloplasty, the intraocular pressure was
      successfully reduced from 23.43+/-5.52 to 12.6+/-1.78 mm Hg (P<0.0001) at the
      final control visit. Topical medication was reduced from 2.9+/-1.1 to 0.4+/-0.6
      over the same period. SC's increase in height was higher than that in width at
      the last visit (height: +351%, P=0.0004, width: +144%, P=0.002). With the UBM the
      SC was easily identifiable by the reflection of the tractions sutures in 75% of
      the patients at the last visit. Transscleral filtration was detectable in 42% of
      the patients at the last visit using AS-OCT and a scleral lake was still
      detectable by OCT in 25% of the patients and even in 42% of the patients by UBM.
      CONCLUSIONS: Persisting anatomic changes of SC, a transscleral filtration and a
      scleral lake can be recorded by AS-OCT and UBM long-term after successful
      canaloplasty.

PMID- 29194202
TI  - Evaluation of Angle Closure as a Risk Factor for Reduced Corneal Endothelial Cell
      Density.

PMID- 29194203
TI  - Relationship Between Open-angle Glaucoma and Stroke: A 2010 to 2012 Korea
      National Health and Nutrition Examination Survey.
AB  - PURPOSE: To determine the relationship between open-angle glaucoma (OAG) and
      stroke in the Korean population. MATERIALS AND METHODS: This study was a
      population-based, cross-sectional study that used data from the Korea National
      Health and Nutrition Examination Survey (KNHANES), a complex, stratified,
      multistage, probability-cluster survey. We analyzed a total of 11,959
      participants who were above 40 years old and were included in the fifth KNHANES
      database (2010 to 2012 data). Weighted prevalence of OAG and stroke in various
      populations were estimated. Univariate and multivariate logistic regressions were
      performed to examine potential risk factors for stroke, including OAG.
      Multivariate adjusted odds ratios (OR) for stroke were examined in subjects with
      and without OAG. Subjects were also examined by hypertension and diabetes status.
      RESULTS: Stroke patients had a significantly higher OAG prevalence (8.5%) than
      nonstroke patients (3.8%; P<0.001). After adjusting for selected risk factors,
      the presence of OAG tended to be associated with stroke (adjusted OR=1.629), but
      this result was not statistically significant (P=0.053). Stroke and OAG were
      significantly associated with each other in subjects with hypertension (OR=2.059;
      P=0.010) and diabetes (OR=2.649; P=0.040). In addition, the associations of
      stroke and other systemic diseases were stronger when OAG was a comorbid
      condition. CONCLUSIONS: Although there was no overall statistical significance,
      patients with OAG had an increased risk of stroke, among those with systemic
      comorbidities, including hypertension and diabetes. Our results may provide
      insight on the underlying mechanisms of OAG and their association with stroke
      development.

PMID- 29194204
TI  - A Retrospective Review Comparing the Safety and Efficacy of 120 Versus 160
      Applications of Selective Laser Trabeculoplasty.
AB  - PURPOSE: To compare the effectiveness and safety of 120 applications versus 160
      applications of selective laser trabeculoplasty (SLT) at reducing intraocular
      pressure (IOP) from baseline in glaucoma patients over a 1-year period. METHODS:
      A retrospective chart review was conducted, comprising 376 eyes from 199 patients
      who underwent SLT treatment performed by the same glaucoma subspecialist from
      2014 to 2015. Data were obtained on patients' clinical features, management, and
      outcomes. Patients were treated with either 120 applications or 160 applications
      of SLT per 360 degrees of trabecular meshwork over 2 sessions. Statistical
      analyses were performed comparing baseline IOP with IOP at 6 weeks and 1-year
      follow-up after completion of treatment. The incidence and severity of transient
      IOP rises immediately post-SLT was also recorded. RESULTS: Both SLT regimes were
      effective at reducing IOP. Univariate t tests showed that the 160 applications
      group had significantly greater mean reduction of IOP from baseline at both 6
      weeks (4.6 vs. 3.6 mm Hg, P=0.015) and 1-year time points (4.1 vs. 2.8 mm Hg,
      P=0.019). However, when multivariate analyses were used to account for the
      effects of clustering and include other covariates such as age, baseline IOP,
      history of previous SLT there was no significant difference between success rates
      of the 2 treatment groups at either time points. Higher baseline IOP was
      associated with greater IOP reduction at 6 weeks (P<0.001) and 1 year (P<0.001)
      for both treatment groups. There was no statistical difference in incidence and
      severity of IOP spikes at 1-hour post-SLT between the 2 treatment groups.
      CONCLUSIONS: SLT produces a significant IOP-lowering effect and treatment with
      160 applications per 360 degrees may be more effective than 120 applications per
      360 degrees. Furthermore, 160 applications of SLT does not increase the risk of
      transient IOP spikes.

PMID- 29194205
TI  - A Protective Eye Shield Reduces Limbal Strain and Its Variability During
      Simulated Sleep in Adults With Glaucoma.
AB  - PURPOSE: To determine the effect of wearing a protective eye shield (mask) on
      limbal strain magnitude and variability in glaucoma eyes when sleeping with 1
      side of the face down (FD) against a pillow. METHODS: A prospective, randomized,
      interventional trial was conducted at the Wilmer Eye Institute with 36 glaucoma
      patients. A contact lens sensor measured limbal strain (output in equivalent
      millivolts) during intervals of up to 60 minutes in lateral decubitus, FD, and
      supine positions. Eighteen subjects wore a mask during 1 of 2 FD intervals, with
      randomized assignment of the interval. Data from additional trials with no mask
      were included in some analyses. In addition, some facial-feature dimensions from
      3D scanned images of 23 subjects were compared with limbal strain data. RESULTS:
      Wearing a mask trends toward a reduced mean change in contact lens sensor output
      (limbal strain) on moving to a FD positions [+34.1 mVeq, P=0.01 reduced by -22.3
      mVeq, P=0.09 (n=36)]. Mask wearing reduced variability in strain while FD [-22.8
      mVeq, P=0.04 (n=18)]. In eyes with past progressive visual field loss, the effect
      of the mask reduced mean strain change when moving to FD [-44.8 mVeq, P=0.02
      (n=31)]. Longer corneal apex to nose-tip and to temple lengths were associated
      with reduced variability while FD [P=0.02 and 0.04, respectively (n=23)].
      Treating both lengths as confounding factors increased statistical significance,
      particularly for analysis of the no-mask change in strain data moving to and from
      the FD position [P=0.004 to 0.002 and P=0.03 to 0.01 (n=23)]. CONCLUSION AND
      RELEVANCE: Wearing a mask reduced limbal strain and variation in limbal strain
      during simulated FD sleep, particularly in eyes with past field worsening, as did
      some facial features.

PMID- 29194206
TI  - Predictive Factors for Visual Field Conversion: Comparison of Scanning Laser
      Polarimetry and Optical Coherence Tomography.
AB  - PURPOSE: The purpose of this study was to compare the ability of scanning laser
      polarimetry (SLP) and spectral-domain optical coherence tomography (SD-OCT) to
      predict future visual field conversion of subjects with ocular hypertension and
      early glaucoma. METHODS: All patients were recruited from the Erlangen glaucoma
      registry and examined using standard automated perimetry, 24-hour intraocular
      pressure profile, and optic disc photography. Peripapillary retinal nerve fiber
      layer thickness (RNFL) measurements were obtained by SLP (GDx-VCC) and SD-OCT
      (Spectralis OCT). Positive and negative predictive values (PPV, NPV) were
      calculated for morphologic parameters of SLP and SD-OCT. Kaplan-Meier survival
      curves were plotted and log-rank tests were performed to compare the survival
      distributions. Contingency tables and Venn-diagrams were calculated to compare
      the predictive ability. RESULTS: The study included 207 patients-75 with ocular
      hypertension, 85 with early glaucoma, and 47 controls. Median follow-up was 4.5
      years. A total of 29 patients (14.0%) developed visual field conversion during
      follow-up. SLP temporal-inferior RNFL [0.667; 95% confidence interval (CI), 0.281
      0.935] and SD-OCT temporal-inferior RNFL (0.571; 95% CI, 0.317-0.802) achieved
      the highest PPV; nerve fiber indicator (0.923; 95% CI, 0.876-0.957) and SD-OCT
      mean (0.898; 95% CI, 0.847-0.937) achieved the highest NPV of all investigated
      parameters. The Kaplan-Meier curves confirmed significantly higher survival for
      subjects within normal limits of measurements of both devices (P<0.001). Venn
      diagrams tested with McNemar test statistics showed no significant difference for
      PPV (P=0.219) or NPV (P=0.678). CONCLUSIONS: Both GDx-VCC and SD-OCT demonstrate
      comparable results in predicting future visual field conversion if taking typical
      scans for GDx-VCC. In addition, the likelihood ratios suggest that GDx-VCC's
      nerve fiber indicator<30 may be the most useful parameter to confirm future
      nonconversion. (http://www.ClinicalTrials.gov number, NTC00494923; Erlangen
      Glaucoma Registry).

PMID- 29194208
TI  - Can You Hear Me Now? Communication Among Physicians and Nursing Students.

PMID- 29194207
TI  - Planning Assignments in Nursing Courses: Be Strategic.

PMID- 29194209
TI  - Connecting With Students Through Creative Teaching.

PMID- 29194210
TI  - Lesbian, Gay, Bisexual, and Transgender Education in Nursing.

PMID- 29194211
TI  - Publishing Trends in Otology and Neurotology.
AB  - OBJECTIVES: 1) Describe publishing trends for otologic/neurotologic disorders
      over a 35-year span. 2) Compare trends in publishing with disease prevalence. 3)
      Evaluate changes in topic and journal specific ranking scores over time. METHODS:
      PubMed searches were performed on 35 otologic/neurotologic disorders using
      medical subject headings (MeSH) terms from 1980 to 2015. Searches were limited in
      scope to the English language. A Mann-Kendall trend analysis evaluated changes in
      publication frequency as a discrete variable while correcting for total number of
      articles published per year. Scopus was used to identify SCImago Country and
      Journal Rank (SJR) indicator scores and weighted-averages used to calculate
      changes over time. RESULTS: The total number of publications on the 35 topics
      increased from 853 in 1980 to a peak of 3,068 in 2013. Otitis media (tau = 
      0.799, p < 0.001) and Meniere's disease (tau = -0.724, p < 0.001) showed strong
      decreasing publication trends. Temporal bone encephaloceles (tau = 0.743, p <
      0.001) and cochlear implants (tau = 0.740, p < 0.001) showed strong increasing
      publication trends. Rapid rise in publications on superior canal dehiscence and
      vestibular migraine illustrate novel diagnoses. The weighted-average SJR score
      increased from 0.816 in 2000 to 1.160 in 2015 (p < 0.001). CONCLUSION: This study
      displays trends in the literature over the past 35 years that are often
      inconsistent with common disorders seen by otologists/neurotologists. Certain
      diagnoses that are currently being researched less commonly continue to impact
      patients with the same regularity. Quality of otologic/neurotologic literature
      has become more reputable with regards to SJR scores.

PMID- 29194213
TI  - Ollier Disease of the Lateral Skull Base.

PMID- 29194212
TI  - Evaluation of Mitoquinone for Protecting Against Amikacin-Induced Ototoxicity in
      Guinea Pigs.
AB  - HYPOTHESIS: Mitoquinone (MitoQ) attenuates amikacin ototoxicity in guinea pigs.
      BACKGROUND: MitoQ, a mitochondria-targeted derivative of the antioxidant
      ubiquinone, has improved bioavailability and demonstrated safety in humans. Thus,
      MitoQ is a promising therapeutic approach for protecting against amikacin-induced
      ototoxicity. METHODS: Both oral and subcutaneous administrations of MitoQ were
      tested. Amikacin-treated guinea pigs (n = 12-18 per group) received water alone
      (control) or MitoQ 30 mg/l-supplemented drinking water; or injected
      subcutaneously with 3 to 5 mg/kg MitoQ or saline (control). Auditory brainstem
      responses and distortion product otoacoustic emissions were measured before MitoQ
      or control solution administration and after amikacin injections. Cochlear hair
      cell damage was assessed using scanning electron microscopy and Western blotting.
      RESULTS: With oral administration, animals that received 30 mg/l MitoQ had better
      hearing than controls at only 24 kHz at 3-week (p = 0.017) and 6-week (p = 0.027)
      post-amikacin. With subcutaneous administration, MitoQ-injected guinea pigs had
      better hearing than controls at only 24 kHz, 2-week post-amikacin (p = 0.013).
      Distortion product otoacoustic emission (DPOAE) amplitudes were decreased after
      amikacin injections, but were not different between treatments (p > 0.05).
      Electron microscopy showed minor difference in outer hair cell loss between
      treatments. Western blotting demonstrated limited attenuation of oxidative stress
      in the cochlea of MitoQ-supplemented guinea pigs. CONCLUSIONS: Oral or
      subcutaneous MitoQ provided limited protection against amikacin-induced hearing
      loss and cochlear damage in guinea pigs. Other strategies for attenuating
      aminoglycoside-induced ototoxicity should be explored.

PMID- 29194214
TI  - Prediction of Vestibular Imbalance in Acute Peripheral Vestibulopathy by
      Measuring Horizontal Ocular Deviation on Magnetic Resonance Imaging.
AB  - OBJECTIVES: The aim of the study is to evaluate whether horizontal ocular
      deviation (OD) from MR imaging in the emergency room (ER) reflects vestibular
      imbalance, by comparing the horizontal OD in patients with acute vestibulopathy
      to controls. STUDY DESIGN: Retrospective review. PATIENTS AND METHODS: A total of
      69 patients with acute unilateral peripheral vestibulopathy and 30 healthy
      subjects were included. Horizontal OD was quantified by using the axial T2
      weighted fast-spin echo (FSE) images of the brain at 1.5 T. In the study group,
      the results of VFTs (videonystagmography [VNG], caloric test, rotary chair test,
      and cervical vestibular evoked myogenic potentials [cVEMP]) were also reviewed.
      The averaged angle of right and left horizontal ODs was compared between patients
      with acute unilateral vestibulopathy and healthy controls. Also, the correlation
      between horizontal OD and results of VFTs was analyzed in the study group.
      RESULTS: The averaged angle of horizontal OD in study group (23.7 degrees  +/-
      11.6 degrees ) was significantly greater than that of control group (4.27 degrees
      +/- 3.7 degrees ) (p < 0.05). Horizontal OD significantly correlated with slow
      phase velocity of spontaneous nystagmus (SN), the value of caloric paresis (CP)
      on caloric testing, rotary chair gain, asymmetry ratio of rotary chair test and
      interaural difference (IAD) of cVEMP, regardless of time intervals between
      magnetic resonance imaging (MRI) and VFTs. CONCLUSIONS: Horizontal OD
      significantly correlated with parameters of VFT which reflect the vestibular
      imbalance. Therefore, horizontal OD can be used as an indicator of unilateral
      peripheral vestibular weakness.

PMID- 29194215
TI  - Cochlear Implant Insertion Axis Into the Basal Turn: A Critical Factor in
      Electrode Array Translocation.
AB  - HYPOTHESIS: An inappropriate insertion axis leads to intracochlear trauma during
      cochlear implantation (CI). BACKGROUND: Few studies assessed the relationship
      between the insertion axis and the electrode scalar location. METHODS:
      Preimplantation cone-beam CT (CBCT) was performed on 12 human temporal bones. In
      five temporal bones, an optimal insertion axis was planned, due to the
      impossibility to attain the ST centerline from the posterior tympanotomy, because
      of facial canal position. In the seven other temporal bones, an inaccurate
      insertion axis was intentionally planned (optimal axis+15 degrees). Automated CI
      array insertion according to the planned axis was performed with a motorized
      insertion tool driven by a navigated robot-based arm. The cochlea and basilar
      membrane were segmented from the preimplantation CBCT and the array segmented
      from the postimplantation CBCT to construct a merged final three-dimensional (3D)
      model. Microscopical and 3D analysis were performed to determine the
      intracochlear trauma at the level of each electrode. RESULTS: A good agreement
      was observed in determining electrode position between microscopic analysis and
      the 3D model (Cohen's kappa k = 0.67). The angle of approach to the ST centerline
      was associated with the number of electrodes inserted into the ST (r = -0.65, p =
      0.02, [95% CI -0.90 to -0.11] Spearman's rank correlation). CONCLUSION: A 3D
      reconstruction model was effective in determining the array position in the
      cochlea scalae. Our data indicate that the angle of approach to the ST centerline
      is a critical factor in intracochlear trauma. Additional studies should be
      conducted to assess the importance of the insertion axis with other array
      designs.

PMID- 29194216
TI  - Gastrostomy Tubes: Care and Feeding.
AB  - Parents often bring their children to the emergency department for adverse events
      with their child's gastrostomy tube or button. This review will discuss the
      possible complications and the methods to handle them.

PMID- 29194217
TI  - CME Review Article.

PMID- 29194218
TI  - Pediatric Emergency Medicine: Legal Briefs.

PMID- 29194219
TI  - Skull Bone/Calvarial Infarction and Spontaneous Epidural Hematoma as Cause of
      Severe Headache in the Emergency Department.

PMID- 29194220
TI  - An (Un)Fortune Cookie: A 2-Year-Old With Altered Mental Status.

PMID- 29194221
TI  - ECGs in the ED.

PMID- 29194222
TI  - Risk Factors for Admission and Prolonged Length of Stay in Pediatric Isolated
      Skull Fractures.
AB  - OBJECTIVES: This study aimed to assess management of pediatric isolated skull
      fracture (ISF) patients by determining frequency of admission and describing
      characteristics associated with patients admitted for observation compared with
      patients discharged directly from the emergency department (ED) and those
      requiring a prolonged hospitalization. METHODS: We evaluated children younger
      than 5 years who presented with ISF using the South Carolina Traumatic Brain
      Injury Surveillance and Registry System data from 2001 to 2011. Outcomes analyzed
      included discharged from ED, admitted for less than 24 hours, and admitted for
      more than 24 hours (prolonged hospitalization). Bivariate analyses and a
      polytomous logistic regression model identified factors associated with patient
      disposition. RESULTS: Five hundred twenty-seven patients met the study criteria
      (ED discharge = 283 [53%]; inpatient <24 hours = 156 [29%]; inpatient >24 hours =
      88 [18%]). The mean length of stay for admissions was 1.9 (SD, 1.5) days. In the
      regression model, ED discharges had greater odds of presenting to levels 2 to 3
      hospitals (level 2: odds ratio [OR], 6.16; 95% confidence interval [CI], 3.66
      10.39; level 3: OR, 30.98; 95% CI, 10.92-87.91) and lower odds of a high poverty
      status (OR, 0.20; 95% CI, 0.10-0.40). Prolonged hospitalizations had greater odds
      of concomitant injuries (OR, 2.21; 95% CI, 1.12-4.36). CONCLUSIONS: Admission
      after ISF is high despite a low risk of deterioration. High-poverty patients
      presenting to high-acuity medical centers are more commonly admitted for
      observation. Only presence of concomitant injuries was clinically predictive of
      prolonged hospitalization. The ability to better stratify risk after pediatric
      ISF would help providers make more informed decisions regarding ED disposition.

PMID- 29194224
TI  - A Population Based Analysis of Melanoma of the External Ear.
AB  - OBJECTIVE: Malignant melanoma accounts for nearly 75% of all skin cancer deaths,
      and the incidence is on the rise in the United States. External ear melanoma
      (EEM) is rare, and there is little long-term data regarding the clinical behavior
      of this melanoma site. This study analyzes the demographic, clinicopathologic,
      and survival characteristics of EEM. METHODS: The SEER database was queried for
      EEM cases from 1973 to 2012 (8,982 cases). Data analyzed included patient
      demographics, incidence trends, and survival outcomes. RESULTS: External ear
      melanoma occurred most frequently in the sixth and seventh decades of life. Mean
      age at diagnosis was 65.5 (+/-16.8) years. However, the incidence of EEM in
      adolescents and young adults (ages 15-39 yr) has increased by 111.9% from 1973 to
      2012. There was a strong male predilection with a male-to-female ratio of 6.40:1.
      The most common histologic subtype was malignant melanoma, NOS (46.8%), followed
      by superficial spreading melanoma (21.4%), and lentigo maligna melanoma (17.9%).
      The majority of cases were localized at the time of presentation (88.0%), with
      rare distant metastasis (1.9%). The most common treatment modality was surgery
      alone (97.6%), followed by surgery with radiotherapy (2.3%). Ten-year disease
      specific survival was better among those treated with surgery alone (90.7%), than
      those treated with surgery with radiotherapy (37.1%) (p < 0.0001). Increasing
      Breslow's thickness and presence of an ulcerating lesion were both associated
      with poorer survival (p < 0.0001). CONCLUSION: This study represents the largest
      cohort of EEM. It has an excellent survival outcome with surgery being the
      treatment of choice.

PMID- 29194225
TI  - Hearing Outcomes After Stereotactic Radiosurgery for Jugular Paraganglioma.
AB  - OBJECTIVE: To describe audiometric outcomes following stereotactic radiosurgery
      (SRS) for jugular paraganglioma (JP). STUDY DESIGN: Retrospective review.
      SETTING: Tertiary referral center. PATIENTS: Patients with pretreatment
      serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery
      [AAO-HNS] Class A or B) and serial post-SRS audiometric follow-up who underwent
      Gamma Knife SRS for JP between 1990 and 2017. INTERVENTION(S): Gamma Knife SRS.
      MAIN OUTCOME MEASURES: Progression to nonserviceable hearing; correlation between
      baseline hearing and treatment parameters with audiometric outcomes. RESULTS: Of
      85 patients with JP who underwent SRS during the study period, 35 (66% female,
      median age 53) had pretreatment serviceable hearing and serial post-treatment
      audiometry available for review. Median tumor volume at the time of treatment was
      7,080 mm, median cochlear point dose was 5.8 Gy (interquartile range [IQR] 4.1 to
      7.3 Gy), and median marginal and maximum tumor doses were 16 and 32 Gy,
      respectively. After a median follow-up of 37 months (IQR 16 to 77 mo), the median
      change in pure-tone average and speech discrimination score in the treated ear
      was -1.2 dB HL/yr (IQR -4.5 to 0.3) and 0%/yr (IQR 0-3.5%), compared with 0.07 dB
      HL/yr (IQR -0.03 to 0.12) and 0 %/yr (IQR 0 to 0%) in the contralateral untreated
      ear. Seven patients developed nonserviceable hearing (AAO-HNS Class C or D) at a
      median of 13.2 months following SRS (IQR 4.8 to 24 mo). Among those who
      maintained serviceable hearing, median audiometric follow-up was 42 months (IQR
      18 to 77 mo). The Kaplan-Meier estimated rates of serviceable hearing at 1, 3,
      and 5 years following SRS were 91%, 80%, and 80%, respectively. Sixty percent of
      patients with pulsatile tinnitus who underwent SRS experienced varying levels of
      symptomatic improvement following treatment. CONCLUSION: The short- and
      intermediate-term risk of progression to nonserviceable hearing following SRS for
      JP is low. Data regarding the impact of cochlear dose from the vestibular
      schwannoma literature should not be freely applied to JP, since the impact of SRS
      parameters on hearing preservation seems to be less significant.

PMID- 29194226
TI  - Success Rate of Tympanic Membrane Closure in the Elderly Compared to Younger
      Adults.
AB  - OBJECTIVE: To assess the effectiveness and safety of tympanoplasty in elderly
      patients and the effect of frailty on the results. STUDY DESIGN: Retrospective
      chart review. SETTING: Tertiary referral center. PATIENTS: Thirty-one ears in 30
      patients aged 65 years and older were included and matched with 31 controls,
      based on the type of surgery, of a pool of 133 patients aged 35 to 55 years.
      INTERVENTION: Therapeutic. MAIN OUTCOME MEASURE: Success was defined as tympanic
      membrane closure and resolution of presenting complaints. Complications were
      assessed. Frailty was defined by assessing multimorbidity and polypharmacy.
      Fisher's exact test was used to compare success and complication rates between
      the age groups. Linear logistic regression analysis using generalized linear
      models was performed on success and complication rate. RESULTS: Success rates in
      both the groups were 84%. Complication rate in the elderly group was 16% versus
      6% in the control group. This difference was not statistically significant in the
      Fisher's exact test. In the generalized linear model analysis age group,
      multimorbidity and polypharmacy had no significant influence on both success and
      complication rate. CONCLUSION: There was no difference in success and
      complication rate in elderly undergoing tympanoplasty compared with younger
      adults. Having multimorbidity or polypharmacy did not correlate with failure of
      the tympanic membrane closure or a higher complication rate.

PMID- 29194227
TI  - Oesophageal or transgastric views for estimating mean pulmonary artery pressure
      with transoesophageal echocardiography: A prospective observational study.
AB  - BACKGROUND: Recent data suggest that in cardiac surgical patients, the pulmonary
      artery acceleration time (PAT) is useful for estimating mean pulmonary artery
      pressure (MPAP) noninvasively with transoesophageal echocardiography (TOE). The
      pulmonary valve can be visualised from multiple echocardiographic windows, but it
      is unclear which, if any, view correlates best with MPAP. OBJECTIVE(S): To
      compare the PAT measured with TOE from oesophageal and transgastric views with
      MPAP obtained invasively with a pulmonary artery catheter. DESIGN: A prospective
      observational study. SETTING: St. Vincent's Hospital, Melbourne, a university
      tertiary referral centre in Australia. PATIENTS: Sixty-three patients having
      cardiac surgery were included in our study. All patients had insertion of both a
      TOE probe and pulmonary artery catheter; this is the routine standard of care in
      our centre. INTERVENTION(S): Nil. MAIN OUTCOME MEASURES: During a period of
      haemodynamic stability, the PAT was measured first from an oesophageal view and
      then immediately after from a transgastric view. The results were then compared
      with the invasively measured MPAP. RESULTS: Simultaneous measurements of MPAP and
      PAT were taken in 63 patients. In two patients, these measurements were not
      possible in the transgastric position due to an inability to visualise the right
      ventricular outflow tract and pulmonary valve. A Bland-Altman analysis of the PAT
      measured from the upper oesophageal and transgastric views showed a mean
      difference of 1 ms and limits of agreement of -18 to 16 ms. The area under the
      receiver operating curves for predicting pulmonary hypertension with PAT were
      upper oesophageal view 0.99 [95% confidence interval (CI), 0.98 to 1.00] and
      transgastric view 0.99 (95% CI, 0.97 to 1.00). The agreement between the results
      from these two views in the diagnosis of pulmonary hypertension (defined as PAT <
      107 ms) was 93.4% with a kappa of 0.85 (95% CI, 0.59 to 1.00). There is an
      inverse curvilinear relationship between PAT and MPAP. Using a cut-off of 107 ms,
      the upper oesophageal view predicted pulmonary hypertension (defined as MPAP > 25
      mmHg) with a sensitivity of 94.7% and specificity of 97.6%. The transgastric view
      predicted pulmonary hypertension with a sensitivity of 89.4% and specificity of
      95.2%. CONCLUSION: Oesophageal and transgastric measurements of PAT have close
      agreement and a similar high ability to discriminate between people with and
      without pulmonary hypertension. The transgastric measurement was unobtainable in
      a small percentage of patients and required more probe manipulation. We would
      recommend PAT measurement in the upper oesophageal view.

PMID- 29194230
TI  - 2017 American Academy of Optometry Ocular Photography Contest.

PMID- 29194229
TI  - Patient-Physician Communication on Medication Cost during Glaucoma Visits.
AB  - SIGNIFICANCE: This article is the first to investigate the nature of medication
      cost discussions between ophthalmologists and glaucoma patients. Only 87 of the
      275 office visits analyzed had a discussion of medication cost. Providers should
      consider discussing medication cost with patients to identify potential cost
      related barriers to medication use. PURPOSE: Glaucoma is an incurable chronic eye
      disease affecting a growing portion of the aging population. Some of the most
      commonly utilized treatments require lifelong use, requiring high patient
      adherence to ensure effectiveness. There are numerous barriers to glaucoma
      treatment adherence in the literature, including cost. The aim of this secondary
      analysis was to describe the frequency and nature of patient-physician
      communication regarding medication cost during glaucoma office visits. METHODS:
      This was a mixed-methods secondary analysis of video-recorded participant office
      visits (n = 275) from a larger observational study of glaucoma communication. We
      analyzed medical information, demographic characteristics, and interviewer
      administrated questionnaires, as well as verbatim transcripts of interviews.
      RESULTS: Only 87 participants discussed medication cost during their glaucoma
      office visit. The majority of the subjects who discussed cost had mild disease
      severity (51%), took one glaucoma medication (63%), and had Medicare (49%) as
      well as a form of prescription insurance (78%). The majority of glaucoma office
      visits did not discuss medication cost, and providers often did not ask about
      cost problems. Of the few conversations related to cost, most focused on
      providers offering potential solutions (n = 50), medical and prescription service
      coverage (n = 41), and brand or generic medication choices (n = 41). CONCLUSIONS:
      Our findings are similar to previous studies showing few patients have
      conversations with providers about the cost of glaucoma medications. Providers
      should consider bringing up medication cost during glaucoma office visits to
      prompt a discussion of potential cost-related barriers to medication use.

PMID- 29194231
TI  - Mechanisms, diagnosis and therapy of hypertension.

PMID- 29194232
TI  - Diverse correlations between fibrosis-related factors and liver stiffness
      measurement by transient elastography in chronic hepatitis B.
AB  - BACKGROUND: Several fibrosis-related factors influence liver stiffness
      measurements (LSM); however, these changes have not been investigated in the
      context of the various disease stages of chronic hepatitis B (CHB). AIM: The aim
      of this study was to assess the correlations between fibrosis-related factors and
      LSM in different disease stages of CHB. PATIENTS AND METHODS: Patients with mild
      CHB (n=305) and cirrhotic hepatitis B (cirrhotic HB) (n=137) were compared with
      determine the relationship between LSM and fibrosis-related factors including
      parameters of liver inflammation [aminotransferase (ALT), aspartate transaminase
      (AST), total bilirubin (Tbil)], albumin, globulin, peripheral blood cells
      (neutrophil granulocytes, red blood cells, platelets), abdominal ultrasound B
      scan parameters including right liver thickness, portal vein inradium, diameter
      of spleen (DS), thickness of spleen (TS), and splenic vein inradium (SV).
      RESULTS: In patients with mild CHB, LSM was correlated strongly with ALT
      (r=0.3534, P<0.0001), AST (r=0.3976, P<0.0001), and ALT+AST (r=0.3760, P<0.0001).
      LSM was correlated closely with Tbil (r=0.2237, P<0.0001), albumin (r=-0.3126,
      P<0.0001), albumin/globulin (r=-0.3086, P<0.0001), SV (r=0.3317, P<0.0001), DS
      (r=0.4157, P<0.0001), and spleen volume (DS*TS) (r=-0.4399, P<0.0001). Red blood
      cells were correlated negatively with LSM in both mild CHB and cirrhotic HB
      patients (r=-0.1981, P=0.0203; r=-0.1593, P=0.0053). LSM was not correlated with
      age, peripheral blood cell parameters, right liver thickness, portal vein
      inradium, or TS in mild CHB or cirrhosis HB patients. However, in patients with
      cirrhotic HB, LSM values were not correlated significantly with other fibrosis
      related factors, except for Tbil (r=0.2272, P=0.0076). CONCLUSION: Our findings
      suggest that the magnitude of these correlations differs significantly between
      mild CHB and cirrhotic HB patients.

PMID- 29194233
TI  - Quality of life related to oral, subcutaneous, and intravenous biologic treatment
      of inflammatory bowel disease: a time trade-off study.
AB  - OBJECTIVES: Novel oral treatments (including biologics) of inflammatory bowel
      disease (IBD) are emerging. Apart from improvement of health, treatment
      convenience may be of value to patients. This 'process utility' can be estimated
      under the quality-of-life framework. We investigated the process utility
      associated with subcutaneous and intravenous biologic treatments compared with a
      hypothetical oral biologic treatment of IBD. MATERIALS AND METHODS: A time trade
      off study to estimate utilities for health states among adult patients with IBD
      was carried out. Respondents rated the anchor state (no description of the route
      of administration; the reference) and three states described: the once-daily
      oral, 2-weekly subcutaneous, and 8-weekly intravenous administration of biologic
      treatment for advanced IBD. RESULTS: Data from 127 respondents (age, 34.4 years;
      women, 52.9%) were collected. The oral state was valuated higher than the anchor
      state more frequently than subcutaneous and intravenous states (P=0.001). The
      process utility of the oral state adjusted for confounders was estimated at 0.147
      (95% confidence interval: 0.087-0.208) and 0.164 (95% confidence interval: 0.096
      0.233) in comparison with subcutaneous and intravenous states, respectively. The
      results were consistent across the respondents irrespective of their
      characteristics and unaffected by the change in the assumptions of data analysis.
      CONCLUSION: Oral administration is preferred over the available routes of
      administration of biologics by patients with IBD. The utility gains from oral
      treatment were significant, indicating higher value of that treatment within a
      cost-utilitarian approach. The additional process-related benefit can justify
      higher expenditures for the research of oral biologics.

PMID- 29194234
TI  - Beyond Admission: Enrollment Management.

PMID- 29194235
TI  - Are You an Original?

PMID- 29194236
TI  - Health Information Technology Scholars Program: From Implementation to Outcomes.
AB  - AIM: This article reports the development, implementation, and outcomes of the
      Health Information Technology Scholars (HITS) program. BACKGROUND: HITS is one of
      nine faculty development collaborative projects funded by the Health Resource
      Service Administration to integrate information and other technologies in nursing
      education and practice. METHOD: In addition to evaluating the content and context
      of the program, the evaluation includes descriptive statistics, goal attainment
      scaling, diffusion of innovation index, utilization of knowledge survey, and
      exemplars from scholars. RESULTS: The HITS program developed 265 faculty across
      132 nursing programs in 43 states over 5 years. HITS scholars impacted more than
      59,000 students and 9,000 other faculty. These technology leaders have numerous
      presentations, publications, and awards. CONCLUSION: Success of the HITS program
      is attributed to the strength of the faculty development collaborative
      partnership, the applicant selection process, and the program design.

PMID- 29194237
TI  - Will BSN Students Consider a Future Nursing Faculty Role?
AB  - AIM: The aim of the study was to determine the intent of baccalaureate nursing
      students to pursue a future nursing faculty role. BACKGROUND: An impending
      nursing faculty shortage negatively affects the capacity to meet the need for
      nurses. METHOD: Using the constructs of social cognitive career theory, a
      prospective correlational research design was used to survey prelicensure BSN
      nursing students regarding their intent for a future nursing faculty role.
      RESULTS: Twenty-five percent of the students intend to pursue a future faculty
      role. The six statistically significant predictors for a future faculty role were
      type of nursing program (OR = 2.0), interest in the activities of a faculty role
      (OR = 2.3), outcome expectations-advantages (OR = 1.9), previous teaching
      experiences (OR = 1.7), encouragement (OR = 1.5), and outcome expectations
      disadvantages (OR = 0.8). CONCLUSION: Providing students with knowledge of the
      faculty role, teaching experiences, and encouragement may inspire them to pursue
      a future faculty role.

PMID- 29194238
TI  - The Effect of a Formal Mentoring Program on Career Satisfaction and Intent to
      Stay in the Faculty Role for Novice Nurse Faculty.
AB  - AIM: The purpose of this mixed-method study was to explore the influence of a
      formal mentoring program on career satisfaction of novice full-time nurse faculty
      in academia. BACKGROUND: The transition from the role of clinician to faculty in
      an academic setting can be challenging for novice nurse faculty. METHOD: A link
      to an electronic survey with open-ended questions was emailed to 1435
      participants. RESULTS: The response rate was 17.6 percent (N = 124). Mean scores
      were obtained, and independent t-test were computed to compare scores of faculty
      who had participated in a mentoring program with scores of nonparticipants.
      Content analysis of the open-ended answers was conducted, and common themes were
      identified. CONCLUSION: By examining characteristics that contribute to the
      success of novice nursing faculty, recruitment and retention of faculty may
      improve, which is essential due to the worsening nursing faculty shortage.

PMID- 29194239
TI  - Traditional and Accelerated Baccalaureate Nursing Students' Self-Efficacy for
      Interprofessional Learning.
AB  - AIM: The aim of the study was to examine self-efficacy among traditional and
      accelerated nursing students with regard to interprofessional learning.
      BACKGROUND: The World Health Organization and other organizations recognize the
      need for interprofessional education to prepare health care providers for
      collaborative practice. Graduates of baccalaureate nursing programs require
      competence in interprofessional collaboration and communication. METHOD:
      Traditional (n = 239) and accelerated (n = 114) nursing students' self-efficacy
      was measured utilizing Mann et al.'s Self-Efficacy for Interprofessional
      Experiential Learning Scale. RESULTS: Accelerated students averaged significantly
      higher than traditional students on the interprofessional team evaluation and
      feedback subscale (p = .006) and overall self-efficacy (p = .041). CONCLUSION:
      Awareness of possible differences between traditional and accelerated nursing
      students with regard to self-efficacy may help faculty develop effective
      interprofessional learning experiences for students in each cohort. Although
      results cannot be generalized, findings from this study provide evidence to guide
      the selection of learning strategies.

PMID- 29194240
TI  - A Literature Review of Research on What Has Become of Accelerated Second-Degree
      Baccalaureate Nursing Graduates.
AB  - BACKGROUND: Accelerated second-degree baccalaureate nursing (ASDBN) programs have
      become popular in the United States as a solution to meet the demand for BSN
      nurses. The research conducted on ASDBN graduates is limited and focuses on
      educational experience or early career outcomes, such as NCLEX-RN pass rates or
      first-year job performance. AIM: This research is designed to provide a better
      understanding of the status of ASDBN graduates two years after completion of the
      BSN program. METHOD: A literature review was conducted focusing on research into
      ASDBN graduates beyond their student experiences or early significant career
      events or outcomes. RESULTS: Surprisingly, only two articles met the interest
      criteria used in this literature review. CONCLUSION: There are clear and
      significant gaps in areas that examine ASDBN graduates beyond the immediate
      postgraduation period.

PMID- 29194241
TI  - Nursing Student Perceptions of Structural Empowerment.
AB  - To meet role expectations for nurses, nurses must feel empowered. Faculty
      contributions to the learning environment for nursing students are critical. A
      descriptive analysis of student perceptions of empowerment within the learning
      environment was conducted using a form of Kanter's Conditions of Work
      Effectiveness Questionnaire; 203 participants from schools in 17 different states
      completed surveys. Subjects demonstrated moderate degrees of structural
      empowerment in their learning environment. This positive finding can be further
      investigated and used to fully prepare future nurses.

PMID- 29194242
TI  - Experiential Teaching Increases Medication Calculation Accuracy Among
      Baccalaureate Nursing Students.
AB  - Safe medication administration is an international goal. Calculation errors cause
      patient harm despite education. The research purpose was to evaluate the
      effectiveness of an experiential teaching strategy to reduce errors in a sample
      of 78 baccalaureate nursing students at a Northeastern college. A pretest
      posttest design with random assignment into equal-sized groups was used. The
      experiential strategy was more effective than the traditional method (t = -0.312,
      df = 37, p = .004, 95% CI) with a reduction in calculation errors. Evaluations of
      error type and teaching strategies are indicated to facilitate course and program
      changes.

PMID- 29194243
TI  - Simulation in an Undergraduate Nursing Pharmacology Course: A Pilot Study.
AB  - This study examined the effectiveness of simulation as a method of teaching
      pharmacological concepts to nursing students; perceptions of satisfaction with
      simulation as a teaching strategy were also evaluated. Second-semester juniors
      participated in three simulations and completed the National League for Nursing
      Student Satisfaction and Self-Confidence in Learning Questionnaire and the
      Student Evaluation of Educational Quality Survey; a control group received
      traditional lectures. A unit exam on anticoagulant therapy content was
      administered to measure effectiveness. Findings support that simulation is as
      effective as traditional lecture for an undergraduate pharmacology course.

PMID- 29194244
TI  - Using Simulation to Enhance Education in an Obstetrical Nursing Course.
AB  - This pilot study describes the effects of a simulation experience on students'
      confidence level and performance in the clinical lab setting. Seven groups of
      students in an obstetrical rotation participated in a postpartum hemorrhage
      scenario. Roles were blindly chosen, and interventions were performed and
      evaluated. The confidence level of the students was assessed prior to and
      following the simulation. Overall confidence levels increased. The best
      performances included placing a Foley catheter and inserting an intravenous
      catheter; the worst performances were documentation and safety.

PMID- 29194245
TI  - Reality Check: Preparing Nursing Students to Respond to Ebola and Other
      Infectious Diseases.
AB  - Escalating uncertainty regarding the international impact of Ebola virus disease
      and other infectious diseases prompted educators to develop interactive,
      multidisciplinary training for senior-level baccalaureate nursing students. A
      three-hour clinical learning session was scheduled within the curriculum. Nurse
      faculty utilized 11 activities to increase students' awareness and understanding
      of the potential and actual impact of Ebola virus disease and other infectious
      diseases. Feedback reflected a positive student experience highlighting several
      key areas related to increased knowledge and confidence. This session highlighted
      the importance of adjusting focus and priorities within curricula to meet core
      baccalaureate essentials and address current public health needs.

PMID- 29194246
TI  - Using National Measures of Patients' Perceptions of Health Care to Design and
      Debrief Clinical Simulations.
AB  - This article describes an innovative approach to using national measures of
      patients' perspectives of quality health care. Nurses from a regional simulation
      consortium designed and executed a simulation using the Hospital Consumer
      Assessment of Healthcare Providers and Systems (HCAHPS) survey to prepare nurses
      to improve care and, in turn, enhance patients' perceptions of care. The
      consortium is currently revising the reporting mechanism to collect data about
      specific learning objectives based on national quality indicator benchmarks,
      specifically HCAHPS. This revision reflects the changing needs of health care to
      include quality metrics in simulation.

PMID- 29194247
TI  - Benefits of Simulation and Role-Playing to Teach Performance of Functional
      Assessments.
AB  - The use of simulation is an innovative teaching strategy that has proven to be
      valuable in nursing education. This article describes the benefits of a
      simulation lab involving faculty role-play to teach baccalaureate nursing
      students how to properly assess the functional status of older adults. Details
      about the simulation lab, which involved functional assessments of two elderly
      community-dwelling residents, are presented, along with student and faculty
      evaluations of this teaching modality.

PMID- 29194249
TI  - Students, Technology, and Teaching: Findings from the 2016 ECAR Report.

PMID- 29194248
TI  - Student Developed and Led Simulation Scenarios.
AB  - Use of simulation in teaching is well established as a viable educational
      technique. Flipped classroom techniques using technology have been shown to
      enhance and deepen knowledge of content. This educational innovation utilized
      both techniques in a second-semester prelicensure nursing course to allow
      students to gain a broader focus on complex patient scenarios and a better
      understanding of simulation as a teaching/learning tool. The project was an
      assigned simulation expectation for a medical-surgical nursing course. Students
      developed a simulation based on the care of patients from their clinical site.

PMID- 29194250
TI  - NLN CNEA Achieves Milestone in Accreditation Services.

PMID- 29194251
TI  - CE Test for "Traditional and Accelerated Baccalaureate Nursing Students' Self
      Efficacy for Interprofessional Learning".

PMID- 29194252
TI  - Cranioplasty With Mandibular Outer Cortex Bone Grafts.
AB  - BACKGROUND: Autologous bone grafts are still the best materials for calvarial
      reconstruction. In the past, rib, iliac crest, and cranial bone have been used
      for the reconstruction of the calvarial defects. However, the use of mandibular
      outer cortex bone graft in calvarial defects reconstruction is poorly reported in
      literature. This study focused on using the mandibular outer cortex bone grafts
      for calvarial defects. METHODS: From October 2004 to July 2016, there were a
      total of 13 patients in this study who underwent cranioplasty with mandibular
      outer cortex bone grafts to reconstruction calvarial defects. All the patients
      were followed up for at least 6 months. RESULTS: The majority of the patients
      were satisfied with the reconstructive outcome. CONCLUSION: The authors consider
      the mandibular outer cortex bone graft can achieve excellent esthetic results in
      selected cranioplasty reconstructions.

PMID- 29194253
TI  - Temporal Flap as an Option for Buconasal Fistula Closure.
AB  - Maxillary defects with buconasal/businusal communications are situations
      difficult to manage and solve. Several treatment options are available on the
      literature, each one with its indication. Temporal muscle flap is one of these
      options, being a technique that requires more experience of the surgeon to be
      properly performed and that is mainly indicated for difficult cases, large
      defects and those nonresponsive to simpler techniques. The main purpose of this
      paper is to report 3 clinical patients of the application of the temporal muscle
      flap for the closure of extensive oral defects. None of the patients had
      necrosis, nervous deficits, or any long-term changes. The authors conclude that
      the use of this flap was shown to be a viable, safe technique with low
      complication and high success rates, which may contribute to the rehabilitation
      of well-indicated patients.

PMID- 29194254
TI  - Anterior Skull Base Tumors: The Role of Transfacial Approaches in the Endoscopic
      Era.
AB  - The basis of craniofacial tumor surgery is complete surgical extirpation,
      preferably en bloc or with free borders. Craniofacial techniques are the gold
      standard and primary strategies in the treatment of anterior skull base tumors.
      In the last decade, the reports favoring results of endoscopic techniques have
      increased. One could conclude that the classical transfacial approaches might
      become useless, but, in fact, there is little research comparing these
      techniques.In this article, the authors present their experience with combined
      craniofacial resection of anterior craniofacial skull base tumors in 9
      consecutive patients between January 2013 and July 2015. This article aims to
      review some of the traditional transfacial approaches, illustrating them with
      this series of surgical patients. Benefits and drawbacks of these approaches are
      discussed.

PMID- 29194255
TI  - The Modified Caldwell-Luc Approach in Retrieval of Accidentally Displaced Root
      into the Maxillary Sinus.
AB  - This clinical study presents a case of root displacement into the maxillary sinus
      that is associated with oroantral communication. A modified Caldwell-Luc
      procedure was performed successfully for the retrieval of the displaced root from
      the maxillary sinus. The aim of this article was to highlight the principles and
      advantages of the modified approach in the management of such a case compared
      with the standard Caldwell-Luc approach.

PMID- 29194256
TI  - Repair of the Nasal Floor by the Cleft Margin Flap in Bilateral Complete Cleft
      Lip.
AB  - Bilateral complete cleft lip deformity has been the most challenging to plastic
      surgeons, and lots of methods of repair have been described in the literature.
      The basic principles are to achieve continuity of the orbicularis oris muscle, a
      balanced Cupid's bow with nasal ala, and a complete reconstruction of the nasal
      floor. The last one is, however, easily neglected. A well-reconstructed nasal
      floor serves as a good support of the nasal cartilage, which minimizes secondary
      deformity. In addition, a nasal floor with sufficient soft tissue and minimal
      contracture makes bone grafting easier in the future. The cleft margin flap was
      first introduced by Tajima in 1983 and used for the nasal floor repair in the
      unilateral complete cleft lip. The authors have used this technique in bilateral
      complete cleft lip repair, and from our practice, tension-free repairs of the
      nasal floors could easily be achieved by the cleft margin flaps. The results were
      satisfying and no significant scar contracture or deformity of the nasal floor
      was observed during follow-up. The authors conclude that the cleft margin flaps
      are viable and alternative choices for the repair of the nasal floors in
      bilateral complete cleft lip without major complications.

PMID- 29194257
TI  - Clinical Significance of Biofilm on Silicone Tubes Removed From Patients With
      Nasolacrimal Duct Stenosis.
AB  - PURPOSE: To determine the relationship between the optical density of biofilms on
      silicone tubes and surgical outcomes. METHODS: A total of 43 silicone tubes from
      33 patients with nasolacrimal duct stenosis were enrolled at 6 months after
      bicanalicular silicone tube intubation. The removed silicone tubes were divided
      into 2 segments. One segment of silicone tube was cultured while the other
      segment was used to measure optical density of biofilm. Each segment was divided
      into 3 pieces according to average normal human nasolacrimal anatomy. The first
      piece was located from puncta to lacrimal sac. The second piece was inside the
      nasolacrimal duct. The third piece was in the nasal cavity. Surgical outcome was
      evaluated at postoperative 12 months based on Munk score and fluorescein dye
      disappearance test. RESULTS: A total of 31 (72.1%) patients were surgically
      successful while 12 (27.9%) patients had surgical failure with persistent
      epiphora. In the second piece of silicone tube, the mean optical density of
      biofilm was 0.2654 nm in the surgical success group and 0.4472 nm in the surgical
      failure group. These results showed statistically significant (P < 0.01)
      difference. The most frequently isolated organism was Staphylococcus aureus in
      the surgical success group (7 of 31 patients, 22.6%). It was Pseudomonas
      aeruginosa in the surgical failure group (6 of 12 patients, 50%). CONCLUSION:
      This is the first study that determines the relationship between biofilm on
      silicone tube and surgical outcome. Biofilm formed on silicone tubes in
      nasolacrimal duct might cause surgical failure.

PMID- 29194258
TI  - Management of Nonsyndromic Skeletal Dysgnathia by Distraction Osteogenesis Long
      Term Follow-Up.
AB  - Distraction osteogenesis has been a paradigm shift in the field of orthognathic
      surgery. Majority of the published cases are those of syndromic patients that
      have been managed using varying treatment protocols. This communication describes
      a patient of 18-year-old male diagnosed with skeletal Class II malocclusion due
      to mandibular retognathism. The patient was taken up for mandibular corpus
      distraction of 10 mm. By this approach the patient was benefitted with good
      esthetic result and functional occlusion. Distraction protocol followed in this
      patient for lengthening of mandibular corpus has resulted in a stable outcome.
      The 2-year follow-up photographs show a stable result both esthetically and
      functionally.

PMID- 29194259
TI  - A Clinical Photographic Method to Evaluate the Need for Helmet Therapy in
      Deformational Plagiocephaly.
AB  - PURPOSE: With an increase in positional plagiocephaly patients, various therapy
      methods have been researched and helmet therapy is the most widely used and
      effective treatment method. To devise a method that would allow medical
      professionals and patients' parents to more easily identify the shape and
      outcomes before and after the therapy. METHODS: This study included 399 patients
      who had helmet therapy from November 2014 to February 2016. Patients wore a cast
      helmet for more than 20 hours per day. A cranial caliper was used to measure
      their head before they wore the helmet (prehelmet), once a month during
      outpatient visits, and 6 months after they stopped wearing the helmet
      (posthelmet). Clinical photographs were taken on a transparent acrylic sheet with
      a grid of 5-mm intervals to measure cranial vault asymmetry (CVA), cranial vault
      asymmetry index (CVAI), and symmetry ration (SR). The patients' photographs were
      then measured twice: first against the background without the grid and then
      against the background with the grid. RESULTS: Average age at prehelmet was 20
      weeks while their average therapy period was 12 weeks. Patients' prehelmet CVA
      was 13.3 mm, and their posthelmet CVA was 3.1 mm. Their prehelmet CVAI was 10.1%,
      and their posthelmet CVAI was 2.1% (P < 0.001). Their overall prehelmet and
      posthelmet SRs were 0.820 and 0.969, respectively (P < 0.001). In addition, the
      measurements based on clinical photographs with and without the grid were
      compared using Fleiss kappa. The results showed kappa = 0.847 and 0.956 when the
      patient was mild, kappa = 0.744 and 0.919 when it was moderate, and kappa = 0.767
      and 0.924 when it was severe (P < 0.001). In all 3 patients, the consistency was
      higher with the grid. CONCLUSION: Since cast helmet manufacturing for positional
      plagiocephaly therapy does not require computed tomography scanning, there is no
      need to administer a sedative, nor does it pose any radiation exposure risk.
      Since the cast helmet is easier to manufacture and operate and is more cost
      effective, it could be used to treat more people. In addition, it would be useful
      for both medical professionals and patients' guardians to use clinical
      photographs with the acrylic sheet with the grid as a method to analyze shapes
      and outcomes before and after therapy, along with traditional CVA and CVAI.

PMID- 29194260
TI  - Facial Anthropometric Evaluation of Unilateral Cleft Lip and Palate Patients:
      Infancy Through Adolescence.
AB  - INTRODUCTION: Craniofacial anthropometric studies measure the differences in
      humans' craniofacial dimensions. The aim of this study was to determine facial
      anthropometric dimensions of newborn to 12-year-old girls with nonsyndromic
      unilateral cleft lip and palate (UCLP). METHODS: In this cross-sectional
      analytical study, data was collected from 65 infant to 12-year old girls with
      UCLP. Digital frontal and profile facial photographs were transferred to a
      computer and desired anthropometric landmarks were traced on each image. Fifteen
      anthropometric parameters were measured which were the angles of facial,
      nasofacial, nasomental, Z, nasolabial, inclination of nasal base and labial
      fissure, nasal deviation, mentocervical, facial convexity and also ratios of
      nasal prominence relative to nasal height, middle to lower facial third, upper
      lip to lower lip height, columellar length relative to upper lip, and incisal
      show relative to incisal width. Pearson coefficient and linear regression were
      used for statistical analysis. RESULTS: Upper lip to lower lip height ratio and
      angles of nasofacial, nasolabial, and facial convexity decreased with the age of
      the patients. In contrast, nasomental angle and the ratios of columellar length
      to upper lip length, middle facial height to lower facial height, and incisal
      show relative to incisal width increased. Other parameters studied did not appear
      to have any significant correlation with age. CONCLUSION: In the girls with UCLP,
      various craniofacial dimensions have different growth rates with some parts
      growing slower than others. Some of the parameters studied were significantly
      correlated with age, thus growth-related curves and equations were obtained and
      presented.

PMID- 29194262
TI  - Application of YL-1 Needle in Chronic Subdural Hematoma Treatment for Super-Aged
      Patients.
AB  - OBJECTIVE: The proportion of the super-aged population (at the age of 80 or
      above) in patients with chronic subdural hematoma (CSDH) and the incidence of
      CSDH of the population have been increasing. Since it is widely accepted that YL
      1 needle is effective in CSDH treatment, this paper aimed to probe into the
      efficacy of YL-1 needle in minimally invasive surgery for super-aged (at the age
      of 80-90) CSDH patients. METHODS: A retrospective analysis on the clinical
      information of 17 super-aged CSDH patients having received the YL-1 needle
      puncture treatment provided by the hospital from May 2012 to December 2016 was
      performed. At the same time, another 19 CSDH patients (ages 60-79) who were
      hospitalized during the same period were randomly selected to form a control
      group. The same surgical treatment was provided for both groups to observe and
      compare the treatment efficacy. RESULTS: The patients of both groups were cured
      and discharged. Among the super-aged patients, there was 1 patient with
      postoperative hematoma recurrence, 1 patient with pneumocephalus, and 1 patient
      with wound infection; among the aged patients, 1 reported postoperative
      recurrence and 2 had pneumocephalus; The average length of stay of the super-aged
      group was 9.235 +/- 2.948 days while that of the aged group was 7.316 +/- 3.660
      days, which showed no statistical difference. CONCLUSION: The YL-1 needle
      puncture treatment is safe and efficacious for both the super-aged and the aged
      CSDH patients.

PMID- 29194263
TI  - The Value of a Photobook in Informing Families About the Cosmetic Results of
      Surgery in Craniosynostosis.
AB  - This paper outlines the development and evaluation of a photobook resource to
      support parents' decision making regarding potential craniofacial surgery for
      their child. The photobook was developed at a UK Craniofacial Unit and consisted
      of preoperative and postoperative photographs of patients with craniosynostosis.
      It was intended to act as a visual adjunct to detailed verbal discussion of
      surgical treatment options. No changes in the uptake rate of surgery were
      detected following the introduction of the photobook. An evaluation of parents'
      views of the photobook indicates that families generally welcomed the resource
      and did not report any adverse responses. Ethical considerations of the use of
      such a resource cannot be discounted, and careful presentation of such a resource
      in the context of a specialist team is recommended.

PMID- 29194264
TI  - Navigation-Assisted Nasal Bone Osteotomy for Malunited Fracture.
AB  - BACKGROUND: Nasal bone osteotomy subjectively judges the position for osteotomy
      by visual inspection and by manual feel using the fingertip. Therefore, the
      outcome depends on the surgeon's experience and mastery of the procedure is
      technically challenging. METHODS: The authors applied a navigation system for the
      intraoperative evaluation of the osteotomy line and reduction position in 5
      patients with malunited nasal bone fracture. The authors performed the operation
      with a temporal bone post developed for otologic surgery using Stealth Station S7
      System (Medtronic, Minneapolis, MN). The suretrack is attached to the bone
      chisel. The authors performed the osteotomies while visualizing the tip of the
      chisel on the monitor.In addition, evaluation of the reduction position was
      performed by insertion of a 23G needle syringe with the suretrack to the nasal
      bone surface. RESULTS: The tip of the bone chisel was visible on the monitor, and
      the authors could perform osteotomies while confirming the position and direction
      of osteotomy. In addition, the reduction position could be visualized clearly on
      the monitor. CONCLUSION: Navigation systems can confirm the 3-dimensional spatial
      relationship around the fracture site in real time, requiring only comparatively
      simple preoperative preparation and intraoperative operation without radiation
      exposure. Therefore, the advantage is that even an inexperienced surgeon can
      perform an accurate evaluation. This would be useful as a guide for young doctors
      and medical students as it would be possible to perform safe and accurate
      osteotomy for old nasal bone fractures.

PMID- 29194265
TI  - Computed Tomographic Artifacts in Maxillofacial Surgery.
AB  - OBJECTIVES: The present study aimed to present 4 cases and to undertake a
      systematic review on the current knowledge of the impact of cone beam computed
      tomographic (CBCT) artifacts on oral and maxillofacial surgical planning and
      follow-up. METHODS: The MEDLINE (PubMed) database was searched for the period
      from February 2004 to February 2017, for studies on the impact of CBCT artifacts
      on surgical planning of oral and maxillofacial surgeries. The PRISMA statement
      was followed during data assessment and extraction. As a result, data extraction
      included information regarding: the use of CBCT to plan or follow-up oral and
      maxillofacial surgeries, presence and type identification of a CBCT artifact, and
      details on the impact of artifacts on image quality and/or surgical planning.
      Four cases were selected to illustrate the topic. RESULTS: The search strategy
      yielded 408 publications in MEDLINE (PubMed). An initial screening of the
      publications was performed using abstracts and key words. After application of
      exclusion criteria, a total of 11 studies were finally identified as eligible to
      be discussed. Studies revealed 3 main types of artifact: beam hardening, streak,
      and motion artifacts. Most of the studies suggest that artifacts significantly
      affect oral and maxillofacial surgical planning and follow-up, despite of
      allowing for identification of metal projectiles in cases of maxillofacial
      trauma. CONCLUSION: CBCT artifacts have a significant impact on oral and
      maxillofacial surgical planning and follow-up.

PMID- 29194266
TI  - Total Cheek Reconstruction Using the Pre-Expanded Medial Arm Flap With Functional
      and Aesthetic Donor Site Closure.
AB  - This clinical study aimed at introducing a reconstructive method for total cheek
      soft tissue defects using the pre-expanded medial arm flap and to maximally
      reduce donor site morbidities simultaneously. A retrospective review of data was
      performed for 3 patients requiring the pre-expanded medial arm flap to
      reconstruct total cheek defects. The donor site in the medial arm was primarily
      closed using a pedicle parascapular or thoracodorsal artery perforator flap. All
      patients had a total unilateral cheek defect after lesion removal. Three pre
      expanded medial arm flaps measuring 17 * 11 cm, 22 * 15 cm, and 20 * 15 cm were
      separately used for cheek defect reconstruction. The donor sites in the medial
      arm were closed using a pedicle parascapular flap, measuring 22 * 9.5 cm, and 2
      pedicle thoracodorsal artery perforator flaps, measuring 22 * 10 cm and 23 * 10
      cm. No major complications occurred in any patient. Patients were followed up for
      3, 12, and 18 months. Patients (and/or their family members) were satisfied with
      the final outcomes. Total cheek defect reconstruction using a pre-expanded medial
      arm flap, with the donor site closed using a pedicle axial back flap, can not
      only provide sufficient tissue for cheek resurfacing, but also guarantee primary
      donor site closure and could be an alternative reconstructive option for patients
      who have a total cheek defect.

PMID- 29194267
TI  - Evaluating of Platelet-Rich Fibrin in the Treatment of Alveolar Cleft With Iliac
      Bone Graft By Means of Volumetric Analysis.
AB  - The purpose of this study was to evaluate the efficiency of platelet-rich fibrin
      usage in the treatment of alveolar cleft with iliac bone graft by means of
      volumetric analysis. In this study, 22 patients with alveolar clefts-including 13
      unilateral and 9 bilateral-were treated with anterior iliac crest bone grafts.
      Patients were divided into 2 groups as control (group A) and platelet-rich fibrin
      (group B) groups. Cone beam computed tomography (CBCT) scans were obtained
      preoperatively and 6 months postoperatively. Three-dimensional reconstructions of
      CBCT images were created by using Mimics software. Preoperative alveolar cleft
      volume and postoperative newly formed bone volume were assessed volumetrically.
      The percentages of preoperative alveolar cleft volume ranged from 0.51 to 2.04
      cm, with a mean volume of 0.98 +/- 0.33 cm. The percentages of newly formed bone
      in group B ranged from 50.70% to 80.09%, with a mean percentage of 68.21 +/-
      10.80%. In Group A, the percentages of bone formation ranged from 47.02% to
      79.23%, with a mean percentage of 64.62 +/- 9.49%. Platelet-rich fibrin can be
      used in the treatment of alveolar cleft with corticocancellous bone graft
      harvested from the anterior iliac crest, but in this study, there was no
      statistically significant difference between the groups for postoperative newly
      formed bone volume (P > 0.05).

PMID- 29194268
TI  - Rapid Anterior Segmental Maxillary Retraction by Compression Osteogenesis.
AB  - Maxillary protrusion is one of the deformities of the upper jaw. Orthodontics and
      orthodontics combined with anterior segmental osteotomy are the common treatment
      strategies for this deformity. The hypothesis of this study was that the
      maxillary bone segment could be gradually moved backward safely by using a tooth
      borne-specific compression device that causes bone compression at the bony
      segment interface after performance of surgical bone cuts in cases of anterior
      maxillary protrusion. Ten patients with skeletal maxillary protrusion were
      treated by modified subapical maxillary osteotomy. Then the protrusion was
      gradually set back and fixed in a new position through the use of a compression
      device. After 8 weeks, the device was removed, and soft and hard tissue was
      evaluated. The average setback of the anterior maxillary segment was found to be
      6.8 mm. The ratio of the upper lip to the maxillary incisor retraction was
      0.52:1. The nasolabial angle increased with a change of 13.5 degrees . The
      mentolabial angle increased with a change of 12.5 degrees . This study is the
      first clinical study in using compression osteogenesis aided by a modified
      anterior subapical maxillary osteotomy technique in the management of skeletal
      maxillary protrusion that considered as an alternative to traditional surgical
      methods and to avoid its complications. It can be used successfully and safely,
      leading to rapid maximum setback of the anterior maxillary segment with great
      contact between bone segment, better and gradual hard and soft tissue remodeling,
      short treatment duration, and avoid using plates and screws with its
      complications.

PMID- 29194269
TI  - Bibliometric Analysis of Journals in the Field of Endoscopic Endonasal Surgery
      for Pituitary Adenomas.
AB  - Endoscopic endonasal surgery for pituitary adenomas is being performed more
      frequently worldwide in the recent years. This first bibliometric analysis was
      conducted aiming to have a microscopic view of research activities about
      endoscopic endonasal surgery for pituitary adenomas. The original articles about
      endoscopic endonasal surgery for pituitary adenomas were extracted from the Web
      of Science (WoS) and analyzed concerning their distributions. We also explored
      the potential correlations between publications of different countries and their
      gross domestic product (GDP) via Pearson correlation test. The total number of
      original articles retrieved from WoS was 307 from 1997 to 2017. The number of
      original articles published in the last decade has increased by 530.95% compared
      with that published in the former decade. The United States has published 124
      articles (40.391%), followed by Italy with 40 (13.029%) and Japan with 27
      articles (8.795%). The journal that published the highest number of original
      articles was Journal of Neurosurgery with 31 (10.098%), followed by Neurosurgery
      (n = 23, 7.492%), World Neurosurgery (n = 23, 7.492%), and Neurosurgical Focus (n
      = 15, 4.886%). There was a strong correlation between publication numbers and GDP
      of different countries (r = 0.889, P < 0.001). There is a skyrocket trend of
      endoscopic endonasal surgery for pituitary adenomas during the last 2 decades,
      and countries with high GDP tend to make more contributions to this field.

PMID- 29194271
TI  - Severe Retrobulbar Pain in an Undiagnosed Patient of Atypical Fracture of
      Sphenozygomatic Region.

PMID- 29194270
TI  - Trend and Demographic Characteristics of Maxillofacial Fractures in Level I
      Trauma Center.
AB  - AIM: The aim of this study was to analyze the pattern and treatment of
      craniomaxillofacial injuries in the northern part of Israel, within a Jewish
      majority and large Arab minority population. PATIENTS AND METHODS: A 5-year
      retrospective study evaluated patients treated for craniomaxillofacial fractures.
      Fracture cause, type, site, and patient demographics were evaluated. RESULTS:
      Patient age ranged from 1 to 94 years with an average age of 36.7 years; 52% of
      the victims were Jews and 48% Arabs. There was male predilection in both sectors
      (78.3% vs 21.7%). The main site of injury was the zygomatic bone (33.5%) followed
      by nasal bone, orbital, mandible, frontal sinus, and maxillary fractures. The
      main etiology of injuries was falls (45.4%) with significantly more falls
      reported by females (52.1% vs 43.2% in males). Motor vehicle accidents caused
      injuries more frequent in males. Arabs experienced CMF fractures at a younger age
      compared to Jews (27.8 and 44.8 average age, respectively). In the elderly, the
      trend reversed where Jews were more prone to craniomaxillofacial fractures.
      CONCLUSIONS: Compared to their weight in the population, the Arab sector
      experiences more craniomaxillofacial injuries. The Jewish elderly population
      tends to reside in nursing homes where they are more susceptible to accidental
      falls, whereas young Arab males are more exposed to motor vehicle accidents and
      interpersonal violence. Falls were the main cause of injuries particularly in
      women. This may reflect the women's fear of reporting domestic violence. We
      believe that increased government investments in infrastructures and education
      will lower the incidence of craniomaxillofacial trauma and balance the gap
      between both sectors and sexes.

PMID- 29194272
TI  - Comparison of Complication Rate Between LeFort III and Monobloc Advancement With
      or Without Distraction Osteogenesis.
AB  - BACKGROUND: LeFort III osteotomies or monobloc advancements, with or without
      distraction, can be used to treat mid-facial hypoplasia causing exorbitism and
      obstructive sleep apnea in syndromic patients. This report is a meta-analysis of
      the complication rates following LeFort III osteotomies or monobloc advancement
      with or without distraction. METHODS: Triple database search was conducted to
      identify articles addressing mid-facial hypoplasia treated with LeFort III or
      monobloc in which complications were detailed. Complications were considered
      major if they required a second operation or were potentially life threatening.
      Statistical analysis was performed with Student t test. RESULTS: Fifteen studies
      fit inclusion criteria. This yielded 363 total patients. In patients treated with
      a monobloc advancement, there was a statistically higher rate of major (P <
      0.0001) and minor (P < 0.0001) complications, death (P = 0.02), cerebrospinal
      fluid (CSF) leaks (P < 0.0001), and meningitis/abscess (P < 0.0001) when
      distraction was used. In patients treated with a LeFort III, there was a
      statistically higher rate of reoperation when distraction was used (P = 0.001).
      In patients treated without distraction, there was a statistically higher rate of
      major (P < 0.0001) complications, death (P = 0.008), CSF leaks (P = 0.003), and
      reoperation (P < 0.0001) with a monobloc and a statistically higher rate of minor
      complications (P < 0.001) with a LeFort III. CONCLUSION: LeFort III proved to be
      a safer technique for the treatment of mid-facial hypoplasia. Although
      distraction was initially introduced to reduce complications, in this review,
      monobloc with distraction had the highest rate of major complications. There are
      multiple confounding factors that influence success of mid-face surgery and every
      patient must be evaluated and treated individually.

PMID- 29194273
TI  - Is Osteoplasty With Unilateral Osteotomy Effective in the Correction of the
      Crooked Nose?
AB  - OBJECTIVE: The crooked nose is frequently observed, and a significant number of
      correction methods have previously been described. Nevertheless, the condition
      remains a challenging problem for rhinoplastic surgeons. Here, the authors
      present a technique that the authors have used to correct a crooked nose in
      selected patients. METHODS: A total of 23 patients underwent surgery for a C
      shaped crooked nose, and were followed up for an average of 11.4 months. Pre- and
      postoperative photographs were taken, and these were analyzed to evaluate the
      results. RESULTS: Osteoplasty and unilateral osteotomy were carried out in all 23
      patients and a spreader graft was contralaterally placed. Unilateral osteoplasty
      was conducted in 17 patients, while bilateral osteoplasty was performed in 6
      patients. In 19 patients, a single spreader graft was sufficient, but it was
      necessary to use a double spreader graft in 4 patients. In summary, 23 C-shaped
      crooked noses were corrected with osteoplasty plus unilateral osteotomy.
      CONCLUSIONS: Osteoplasty plus unilateral osteotomy, combined with a contralateral
      spreader graft, is an efficient method that can be safely used in the correction
      of a C-shaped crooked nose.

PMID- 29194274
TI  - A Stratified Algorithm for Skull Base Reconstruction With Endoscopic Endonasal
      Approach.
AB  - The authors presented our institutional experience with skull base reconstruction
      techniques and developed a stratified algorithm for different causes of
      cerebrospinal fluid (CSF) leak. This is a retrospective review of patients who
      were diagnosed as CSF leak treated with skull base reconstruction or who
      underwent endoscopic transsphenoidal surgery for sellar and parasellar lesions at
      our department from August 2012 to April 2017. The authors totally identified 57
      (59 operations in total) patients who were divided into 3 groups according to the
      causes of CSF leak and different reconstruction techniques. All patients
      underwent skull base reconstruction with specific focus on diagnosis,
      reconstruction techniques and strategies, and clinical outcome. The
      reconstruction technique we adopted was the classical multiple-layer technique,
      as known as "sandwich" technique, with combination of fat tissue, septal bone,
      autologous fascia lata, artificial dura, and nasoseptal flap (NSF). The NSF was
      selectively harvested for large defects according to our protocol. The
      reconstruction failure rate is 4.4% (2 of 45) in patients underwent endoscopic
      surgery for sellar and parasellar lesions. Reconstruction for postoperative
      iatrogenic, traumatic, and spontaneous CSF leak achieved 100% success rate; 54.2%
      (32 of 59) operations were done with "sandwich" plus NSF. The overall failure
      rate of all reconstructions was 3.4% (2 of 59). A stratified approach with
      multiple-layer technique and NSF is reliable for skull base reconstruction.

PMID- 29194275
TI  - Preoperative Exposure of Sigmoid Sinus Trajectory in Posterolateral Cranial Base
      Approaches Using a New Landmark Through a Neurosurgical Perspective.
AB  - The location of burr holes in posterolateral cranial base approaches should be
      appropriate to provide an adequate operative field, and surgical freedom is
      crucial for bone window opening. The aim of this study was to search for more
      convenient and easily detectable landmarks in comparison with current landmarks
      in posterolateral cranial base surgery. Twenty 3-dimensional reconstructed head
      and neck computed tomography angiography images (group 1) and 20 cadaver heads
      (group 2) were evaluated. An imaginary line connecting the angle of the mandible
      and the mastoid tip was extended upward. A second line passing through the
      lateral edge of the zygomatic arch was also extended posteriorly. The authors
      examined if the first line met with the sigmoid sinus throughout its course and
      determined the location of the intersection point of these 2 lines relative to
      the sigmoid-transverse sinus junction. The intersection point did not correspond
      to the sinus region in 3 images from group 1 and 4 specimens from group 2. The
      matching of the mandibula-mastoid line trajectory with the sigmoid sinus course
      was unacceptable in 4 images and 5 cadavers. For venous anatomy preservation and
      anatomic skull base fossa orientation during posterolateral cranial base
      approaches, upward extension of the mandibula-mastoid line can be a proper
      landmark for surgical planning in this region. The authors' proposed superficial
      anatomical line and intersection point over the skull could be used as a reliable
      indicator for the external projection of the sigmoid sinus and an appropriate
      initial burr-hole location.

PMID- 29194276
TI  - Modified Backward Avulsion Used in the Treatment of Third-Branch Primary
      Trigeminal Neuralgia.
AB  - OBJECTIVE: A clinical retrospective study was performed to observe the clinical
      effect of a modified surgical treatment for third-branch primary trigeminal
      neuralgia. METHOD: Thirty patients who had suffered from neuralgia for several
      years underwent modified backward avulsion of the inferior alveolar nerve and
      were followed for 3 to 5 years. In this technique, the inferior alveolar nerve
      was cut off through the mandibular wisdom tooth extraction socket or the
      corresponding alveolar ridge window and was avulsed from the mental foramen.
      Simultaneously, the neural foramen was packed with autogenous bone fragments to
      prevent recurrence. RESULTS: After a 3- to 5-years follow-up, 19 patients were
      cured, 8 patients reported a partial effect of treatment, and 3 patients
      exhibited recurrence. The efficacy rate was 90%. Postoperatively, the patients
      had different degrees of numbness in the area innervated by the third branch of
      the trigeminal nerve but did not have any other complications. CONCLUSIONS: This
      study proved that modified backward avulsion is a simple, effective, and safe
      method that can be applied in the clinical setting to treat third-branch primary
      trigeminal neuralgia.

PMID- 29194278
TI  - Craniosynostosis Surgery and the Impact of Tranexamic Acid Dosing.
AB  - Consensus does not exist regarding the best dosage regimen for using tranexamic
      acid (TXA) for patients undergoing open calvarial vault remodeling in
      craniosynostosis surgery. The purpose of this study was to evaluate 2 dosing
      protocols, as well as the cost of using TXA. Previously, the institutional
      protocol was to give patients undergoing open calvarial vault remodeling a
      loading infusion of TXA (10 mg/kg) at the start of their procedure, after which
      intravenous TXA (5 mg/kg/h) was given throughout surgery and for 24 hours
      postoperatively. In July 2015, the protocol changed to a reduced postoperative
      infusion time of 4 hours. A retrospective review was conducted of records of 30
      patients who had surgery before the protocol change (24-hour group) and 23
      patients whose surgery occurred after the protocol change (4-hour group). The
      following data were collected: blood volume transfused, hemoglobin levels,
      estimated blood loss, and intensive care days; and costs of TXA and blood
      transfusion. Results showed a 4-hour infusion was as effective as a 24-hour
      infusion for reducing blood loss in patients undergoing craniosynostosis.
      Transfusion requirements, hemoglobin and hematocrit levels, and estimated blood
      loss were not significantly different for the groups. The cost of TXA and
      transfusion in the 4-hour group was significantly less (P < 0.001) than in the 24
      hour group. No significant difference in cost existed for patients who received
      blood transfusion alone versus patients who received the 4-hour TXA infusion.

PMID- 29194279
TI  - Cutaneous Metastases of the Glioma.
AB  - Low grade glioma (LGG) is a very common primary brain neoplasm with a very good
      prognosis and the median survival of patients is approximately 8 years. With the
      development of current treatments such as surgery resection, radiotherapy, and
      chemotherapy, the recurrence rate and the distant metastasis rate of LGGs are
      largely decreased. Extracranial metastases are seldom happened. However, the
      authors present a pathologically proven patient with scalp metastasis, which was
      metastasized from LGG occurring site to the surgical scar 8 months following
      initial craniotomy and chemotherapy. The histopathologic examination of the
      primary site and the recurrent under the scalp are exactly similar. This grade of
      glioma was increased along with cutaneous metastases. A discussion of a series of
      the extracranial metastases of the glioma, especially for the surgical
      considerations, is also provided advice for the cutaneous metastases of the
      glioma.

PMID- 29194280
TI  - Conization and healthcare use: a population-based register study.
AB  - The aim of this study was to assess whether negative psychological consequences
      of conization reported in questionnaire studies translated into increased use of
      the healthcare services that could relieve such symptoms. This was a population
      based register study comparing women undergoing conization with a control group
      of women with normal cytology results. Data were derived from Danish registers.
      Using the difference-in-differences method, we measured contacts with general
      practitioners (GPs), hospitals, psychiatrist/psychologists, and use of anxiolytic
      and antidepressant prescription drugs over 5 years 'before' and 'after' the
      conization in the study group, and in comparable periods in the control group.
      During the 'before' period, women who later had a conization had greater contact
      with GPs and hospitals, and slightly more contact with
      psychiatrist/psychologists, than control women. In both groups, healthcare use
      increased significantly from the 'before' to the 'after' period. For contacts
      with GPs and hospitals, the increase was significantly larger for the conization
      group than for the control group, but this could be attributed to the standard
      postconization follow-up process. In the 'before' period, women who later had a
      conization used fewer drugs than women of the control-group, but their drug use
      increased similarly over time. The conization event did not result in an
      increased use of the healthcare services that could relieve potential negative
      side effects. However, women who underwent a conization seemed to constitute a
      select group as they already used GPs and hospitals more frequently, and
      anxiolytic and antidepressant drugs less frequently, than other women in the
      years 'before' the conization event.This is an open-access article distributed
      under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives
      License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work
      provided it is properly cited. The work cannot be changed in any way or used
      commercially without permission from the journal.
      http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 29194282
TI  - Frequency and Characterization of Tracheal Intubation Adverse Events in Pediatric
      Sepsis.
AB  - OBJECTIVES: Intubation in critically ill pediatric patients is associated with
      approximately 20% rate of adverse events, but rates in the high-risk condition of
      sepsis are unknown. Our objectives were to describe the frequency and
      characteristics of tracheal intubation adverse events in pediatric sepsis.
      DESIGN: Retrospective cohort study of a sepsis registry. SETTING: Two tertiary
      care academic emergency departments and four affiliated urgent cares within a
      single children's hospital health system. PATIENTS: Children 60 days and older to
      18 years and younger who required nonelective intubation within 24 hours of
      emergency department arrival. Exclusion criteria included elective intubation,
      intubation prior to emergency department arrival, presence of tracheostomy, or
      missing intubation chart data. INTERVENTIONS: Not applicable. MEASUREMENTS AND
      MAIN RESULTS: The outcome was tracheal intubation adverse event as defined by the
      National Emergency Airway Registry Tool 4 KIDS. During the study period, 118 of
      2,395 registry patients met inclusion criteria; 100% of intubations were
      successful. First attempt success rate was 57% (95% CI, 48-65%); 59% were
      intubated in the emergency department, and 28% were intubated in the PICU. First
      attempts were by a resident (30%), a fellow (42%), attending (6%), and
      anesthesiologist (13%). Tracheal intubation adverse events were reported in 61
      (43%; 95% 43-61%) intubations with severe tracheal intubation adverse events in
      22 (17%; 95 CI, 13-27%) intubations. Hypotension was the most common severe event
      (n = 20 [17%]) with 14 novel occurrences during intubation. Mainstem bronchial
      intubation was the most common nonsevere event (n = 28 [24%]). Residents,
      advanced practice providers, and general pediatricians in urgent care settings
      had the lowest rates of first-pass success. CONCLUSIONS: The rates of tracheal
      intubation adverse events in this study are higher than in nonelective pediatric
      intubations in all conditions and highlight the high-risk nature of intubations
      in pediatric sepsis. Further research is needed to identify optimal practices for
      intubation in pediatric sepsis.

PMID- 29194281
TI  - RBC Transfusions Are Associated With Prolonged Mechanical Ventilation in
      Pediatric Acute Respiratory Distress Syndrome.
AB  - OBJECTIVES: Blood products are often transfused in critically ill children,
      although recent studies have recognized their potential for harm. Translatability
      to pediatric acute respiratory distress syndrome is unknown given that hypoxemia
      has excluded pediatric acute respiratory distress syndrome patients from clinical
      trials. We aimed to determine whether an association exists between blood product
      transfusion and survival or duration of ventilation in pediatric acute
      respiratory distress syndrome. DESIGN: Retrospective analysis of prospectively
      enrolled cohort. SETTING: Large, academic PICU. PATIENTS: Invasively ventilated
      children meeting Berlin Acute Respiratory Distress Syndrome and Pediatric Acute
      Lung Injury Consensus Conference Pediatric Acute Respiratory Distress Syndrome
      criteria from 2011 to 2015. INTERVENTIONS: We recorded transfusion of RBC, fresh
      frozen plasma, and platelets within the first 3 days of pediatric acute
      respiratory distress syndrome onset. Each product was tested for independent
      association with survival (Cox) and duration of mechanical ventilation (competing
      risk regression with extubation as primary outcome and death as competing risk).
      A sensitivity analysis using 1:1 propensity matching was also performed.
      MEASUREMENTS AND MAIN RESULTS: Of 357 pediatric acute respiratory distress
      syndrome patients, 155 (43%) received RBC, 82 (23%) received fresh frozen plasma,
      and 92 (26%) received platelets. Patients who received RBC, fresh frozen plasma,
      or platelets had higher severity of illness score, lower PaO2/FIO2, and were more
      often immunocompromised (all p < 0.05). Patients who received RBC, fresh frozen
      plasma, or platelets had worse survival and longer duration of ventilation by
      univariate analysis (all p < 0.05). After multivariate adjustment for above
      confounders, no blood product was associated with survival. After adjustment for
      the same confounders, RBC were associated with decreased probability of
      extubation (subdistribution hazard ratio, 0.65; 95% CI, 0.51-0.83). The
      association between RBC and prolonged ventilation was confirmed in propensity
      matched subgroup analysis. CONCLUSIONS: RBC transfusion was independently
      associated with longer duration of mechanical ventilation in pediatric acute
      respiratory distress syndrome. Hemoglobin transfusion thresholds should be tested
      specifically within pediatric acute respiratory distress syndrome to establish
      whether a more restrictive transfusion strategy would improve outcomes.

PMID- 29194283
TI  - Cosmetic Adolescent Filler: An Innovative Treatment of the "Selfie" Complex.
AB  - PURPOSE: "Selfie" photography is increasing among teenagers, accentuates
      congenital anomalies, and impacts self-confidence. Tear trough deformity is most
      commonly due to aging, but also occurs as a congenital anomaly and can be a major
      source of insecurity and embarrassment. OBJECTIVE: The purpose of this study is
      to show the efficacy and safety of hyaluronic acid gel filler in a teenage
      patient with congenital tear trough deformity. MATERIAL AND METHOD: We describe
      the case of a teenager who underwent hyaluronic acid gel filling to the tear
      trough deformity at age 14 years. Prospective follow up was assessed for 5 years.
      RESULTS: The patient improved clinical appearance and self confidence. Her
      satisfaction level was high, and no complication occurred during entire follow
      up. CONCLUSION: In this case, hyaluronic gel acid filler was safe and effective
      for augmentation of congenital tear trough. The patient was satisfied and
      experienced increased self-esteem.

PMID- 29194284
TI  - Koebner Phenomenon Triggered by External Dacryocystorhinostomy Scar in a Patient
      With Psoriasis: A Case Report and Literature Review.
AB  - Koebner phenomenon is the development of isomorphic pathologic lesions on a wound
      of a patient with preexisting cutaneous disease, most commonly psoriasis. An
      elderly male with palmoplantar psoriasis developed periocular psoriasis in the
      form of blepharitis and conjunctivitis following an external
      dacryocystorhinostomy as a manifestation of Koebner phenomenon. Immediate
      diagnosis and treatment with topical steroids led to complete recovery. Thus, the
      authors report the first case of Koebner phenomenon in ophthalmic literature,
      with a review of previously published postsurgical cases of Koebnerization in
      psoriasis patients. All surgeons should be aware of its existence and warn
      susceptible patients regarding its occurrence.

PMID- 29194285
TI  - Endoscopic Corneal Neurotization: Technique and Initial Experience.
AB  - PURPOSE: The authors describe a minimally invasive surgical technique to re
      establish corneal sensibility in a patient with neurotrophic keratopathy with the
      supraorbital nerve harvested endoscopically. METHODS: Pedicled contralateral
      supraorbital nerve was harvested endoscopically through small eyelid crease and
      scalp incisions and transferred to the affected eye. RESULTS: Endoscopic corneal
      neurotization was successfully performed with restoration of corneal sensibility
      and corneal epithelial integrity. CONCLUSIONS: The use of an endoscope allows for
      a minimally invasive approach to successful corneal neurotization with the
      supraorbital nerve.

PMID- 29194286
TI  - Desmoplastic Melanoma of the Periorbital Region.
AB  - Desmoplastic melanoma (DM) is a rare subtype of melanoma and an even smaller
      proportion of periocular melanomas. Here, the authors report 2 cases of DM in the
      periocular region. Staged according to the American Joint Committee on Cancer
      (AJCC) eighth edition classification, patient 1 presented with a stage IIIC
      (pT4apN1cM0) DM in the left lateral canthus with upper and lower eyelid and
      patient 2 presented with a stage IIIB (T4aN1bM0) DM in the left brow and
      supraorbital region with a parotid lymph node metastasis. In both patients, the
      lesions were amelanotic, with inflammatory appearance, and had been noted for
      several years before the correct diagnosis was made. In both patients, wide
      excision led to large surgical defects, and perineural invasion prompted adjuvant
      radiation therapy postoperatively. Patient 2 was treated with an immune
      checkpoint inhibitor for his parotid metastasis. Ophthalmologists should be aware
      of DM, its neurotrophic nature, and potential to metastasize with locally
      advanced lesions.

PMID- 29194287
TI  - Expression of ADAMTS2 and ADAMTS5 in the salivary gland of rats after radioiodine
      therapy.
AB  - OBJECTIVE: The aim of this study was to investigate the presence of ADAMTS2 and
      ADAMTS5 in the salivary gland (SG) of rats after high-dose radioiodine therapy.
      METHODS: A total of 36 male Wistar albino rats were used for this study. Thirty
      six male rats were divided randomly into six groups: control and five radioactive
      iodine (RAI) treatment groups of six rats each. All animals were killed. The
      evaluation of biodistribution and histopathological studies were carried out on
      the SGs removed. Real-time PCR and immunohistochemical analysis were carried out
      to determine mRNA and protein expression levels of ADAMTS genes. Differences
      between the groups were evaluated statistically. RESULTS: In RAI-treated groups,
      ADAMTS2 and ADAMTS5 gene expression was observed to increase, whereas there was
      no mRNA or protein expression in the control group. There were statistically
      significant increases in the mRNA expression of ADAMTS2 (all RAI-administered
      groups in parathyroid gland and at 4, 24, and 48 h in submandibular gland) and
      ADAMTS5 (all RAI-administered groups, except on the 30th day in the parathyroid
      gland and all RAI groups in submandibular gland). Through immunohistochemical
      analysis, the staining pattern in the extracellular source was also observed in
      the overexpressed ADAMTS2 and ADAMTS5 groups. Nuclear coarsening and partial
      focal subnuclei vacuolization were determined in all RAI-administered groups with
      histopathological examinations. CONCLUSION: An increase in the mRNA expression
      levels of ADAMTS2 and ADAMTS5 genes was detected in the RAI-administered groups.
      These results suggested that ADAMTS2 and ADAMTS5 genes might play a role in
      radiation exposure and radioiodine-induced SG changes.

PMID- 29194288
TI  - Area at risk can be assessed by iodine-123-meta-iodobenzylguanidine single-photon
      emission computed tomography after myocardial infarction: a prospective study.
AB  - BACKGROUND: Myocardial salvage is an important surrogate endpoint to estimate the
      impact of treatments in patients with ST-segment elevation myocardial infarction
      (STEMI). AIM: The aim of this study was to evaluate the correlation between
      cardiac sympathetic denervation area assessed by single-photon emission computed
      tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and
      myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold
      standard). PATIENTS AND METHODS: A total of 35 postprimary reperfusion STEMI
      patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates
      cardiac sympathetic denervation) and thallium-201 (evaluates myocardial
      necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion
      recovery for AAR and postgadolinium T1-weighted phase sensitive inversion
      recovery for scar assessment. RESULTS: I-MIBG imaging showed a wider denervated
      area (51.1+/-16.0% of left ventricular area) in comparison with the necrosis area
      on thallium-201 imaging (16.1+/-14.4% of left ventricular area, P<0.0001). CMR
      and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a
      good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with
      the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002).
      Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable
      myocardium) was significantly higher than by CMR (P=0.02). CONCLUSION: In
      patients with STEMI, I-MIBG SPECT, assessing cardiac sympathetic denervation may
      precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

PMID- 29194289
TI  - Lack of Detection of New Amphetamine-Like Drugs Using Conventional Urinary
      Immunoassays.
AB  - BACKGROUND: The number of reports of serious adverse effects and intoxication
      after the use of the new drug 4-fluoroamphetamine (4-FA) increases. At the
      Emergency Department of the OLVG-Oost Hospital in Amsterdam, an on-site drug
      test, the Triage TOX Drug Screen, is available to assist in a rapid diagnosis. In
      less urgent cases, an EMIT II Plus immunoassay is used to determine
      semiquantitatively the presence of drugs of abuse (DOA). The antibodies in these
      immunoassays are designed to detect classic DOA and its urinary metabolites.
      Amphetamine-like drugs that may cause serious toxicity or impairment may not
      cross-react with the available immunoassay kits, and therefore may stay
      undetected. The question arises as to whether 4-FA and paramethoxymethamphetamine
      (PMMA) are detectable in the toxicological screening procedures commonly used for
      testing in urine. METHODS: Synthetic urine was spiked with the drug under
      investigation to create spiking standards of 50, 100, 250, 500, 2500, and 5000
      ng/mL. Urine drug screens were performed on the automated analyzer Biosite Triage
      MeterPro using the Triage TOX Drug Screen test and on a Siemens Drug Testing
      System Viva-E using the EMIT II Plus Ecstasy Assay and the EMIT II Plus
      Amphetamines Assay. RESULTS: In this concentration range, the EMIT II Plus did
      not screen positive for PMMA, but there was some cross-reactivity for PMMA on the
      EMIT II Plus Ecstasy assay. The Triage TOX Drug Screen did test positive for PMMA
      at a concentration of 2500 ng/mL. The EMIT II Plus Amphetamines did test positive
      for 4-FA at a concentration of 5000 ng/mL, whereas the Ecstasy [3,4
      methylenedioxymethamphetamine (MDMA)] assay only showed low cross-reactivity for
      4-FA. The Triage TOX Drug Screen did not test positive for 4-FA. CONCLUSIONS: The
      available immunoassays lack sensitivity to detect 4-FA and PMMA in lower urine
      concentrations. Awareness of the fact that novel DOA may lead to false-negative
      urinary drug tests is of great importance.

PMID- 29194290
TI  - Ultrasound Identifies Broken Drainage Tube Postthyroidectomy.
AB  - Drains are routinely used after thyroidectomy and lateral neck dissection. In
      rare cases, the drainage tube is broken and retained in the neck. It is difficult
      to identify the sonographic features of the remnant tube due to variable reasons.
      However, through comparative and phantom observations, we noticed the double
      tract sign of the tube wall and drainage holes as the key points to solving this
      problem. We report such a case of the ultrasound-guided localization of a broken
      drainage tube that was retained in the patient.

PMID- 29194291
TI  - The Great Mimicker: Pseudo-Meig Syndrome in a Pregnant Patient. A Review.
AB  - Meig syndrome is the triad of benign ovarian tumor, ascites, and pleural
      effusion. Pseudo-Meig syndrome mimics the Meig syndrome triad; however, in pseudo
      Meig syndrome, the ovarian tumor usually represents a primary malignancy or
      metastases. Differentiating Meig from pseudo-Meig syndrome is challenging both
      clinically and with diagnostic imaging but is important because prognoses for
      these distinct entities are drastically different. Evidence-based sonographic
      prediction models are valuable because they can aid in this distinction. Here, we
      present the first reported case of pseudo-Meig syndrome secondary to large,
      bilateral Krukenberg tumors of unknown origin, in a gravid 30-year-old woman at
      24 weeks' gestation, discovered initially by ultrasound.

PMID- 29194292
TI  - Fetal Splenomegaly: A Review.
AB  - Enlargement of the fetal spleen is usually found secondary to systemic diseases
      and is frequently associated with hepatomegaly. By far, the most common causes of
      fetal splenomegaly are infectious. Other etiologies responsible for this sign are
      hemolytic anemia, congestive cardiac failure, metabolic disorders, and rarely,
      leukemia, lymphoma, and histiocytosis.We report a case of prenatal splenomegaly
      diagnosed at 35 weeks, confirmed in the postnatal period. The postnatal workup
      showed the newborn had a familial type 3 form of hemophagocytic
      lymphohistiocytosis (HLH).Hemophagocytic lymphohistiocytosis is an aggressive and
      life-threatening syndrome of excessive immune activation. The genes implicated in
      the hereditary forms of the disease act in an autosomal recessive fashion.

PMID- 29194293
TI  - Multiple pathological mechanisms contribute to hippocampal damage in the
      experimental autoimmune encephalomyelitis model of multiple sclerosis.
AB  - Emotional and cognitive deficits and associated hippocampal damage observed in
      multiple sclerosis (MS) are now recognized as primary disease manifestations.
      However, the pathological substrate of these dysfunctions is unclear. In the
      experimental autoimmune encephalomyelitis (EAE) MS model, impaired hippocampal
      dependent functions are concomitant with severe microglial reactivity and
      neurodegeneration, but reports vary with respect to evidence of lymphocytic
      infiltration, raising questions as to the nature of the underlying
      neurodegenerative mechanisms. Our investigations of EAE-induced inflammation
      across the hippocampal formation showed CD3 infiltration only in regions adjacent
      to inflamed meningeal membranes interposed between the ventral aspect of the
      hippocampus and the dorsal aspect of the mid-brain, but widespread microglial
      reactivity across the structure. Regions that contact the lateral ventricles do
      not show inflammation, but CD3 cells are observed in the adjacent ventricular
      space and choroid plexus, suggesting that microglial reactivity in these regions
      results from exposure to proinflammatory mediators released into the ventricles.
      These data indicate that multiple pathophysiological mechanisms underlie
      hippocampal damage during EAE. Treatment with the immunomodulator FTY720
      eliminates microglial reactivity across the whole structure, suggesting potential
      benefit for neuropsychological symptoms in MS.

PMID- 29194294
TI  - Task switching following 24 h of total sleep deprivation: a functional MRI study.
AB  - Task switching is a ubiquitous feature of many human activities that involve
      multitasking. In addition, owing to occupational demands, many individuals are
      required to engage in task switching under various levels of sleep deprivation,
      such as those who work in military and medical contexts. Nevertheless, little is
      known about the effects that sleep loss has on the neural bases of task
      switching. To address this shortcoming, we administered a cued switching task to
      participants following a night of normal sleep and also following a night of
      total sleep deprivation - in counterbalanced order. The behavioral results
      demonstrated a cost (i.e. longer reaction time) both as a function of sleep
      deprivation and task switching. Sleep deprivation resulted in greater activation
      in the frontoparietal network, whereas task switching was correlated with greater
      activation in the thalamus and superior temporal gyrus. However, despite
      increases in fatigue and sleepiness and a reduction in cognitive effectiveness
      (computed from actigraphic data), the reaction time cost associated with
      switching (i.e. switch cost) was not exacerbated by sleep deprivation. The
      results are discussed in terms of the involvement of executive functions in
      mitigating the effects of sleep deprivation on task switching.

PMID- 29194295
TI  - The Art of Faculty Searches.

PMID- 29194296
TI  - The Homeless Manuscript.

PMID- 29194297
TI  - A Crisis in Competency: The Strategic and Ethical Imperative to Assessing New
      Graduate Nurses' Clinical Reasoning.
AB  - AIM: The aim of the study was to assess entry-level competency and practice
      readiness of newly graduated nurses. BACKGROUND: Literature on success of new
      graduates focuses primarily on National Council of State Boards of Nursing
      Licensure Examination (NCLEX-RN) pass rates, creating a false and incomplete
      picture of practice readiness. METHOD: Posthire and prestart Performance-Based
      Development System assessments were administered to more than 5,000 newly
      graduated nurses at a large midwestern academic medical center between July 2010
      and July 2015. RESULTS: Aggregate baseline data indicate that only 23 percent of
      newly graduated nurses demonstrate entry-level competencies and practice
      readiness. CONCLUSION: New data suggest that we are losing ground in the quest
      for entry-level competency. Graduates often are underprepared to operate in the
      complex field of professional practice where increased patient acuity and
      decreased length of stay, coupled with a lack of deep learning in our academic
      nursing programs, have exacerbated a crisis in competency.

PMID- 29194298
TI  - Establishing Inter- and Intrarater Reliability for High-Stakes Testing Using
      Simulation.
AB  - AIM: This article reports one method to develop a standardized training method to
      establish the inter- and intrarater reliability of a group of raters for high
      stakes testing. BACKGROUND: Simulation is used increasingly for high-stakes
      testing, but without research into the development of inter- and intrarater
      reliability for raters. METHOD: Eleven raters were trained using a standardized
      methodology. Raters scored 28 student videos over a six-week period. Raters then
      rescored all videos over a two-day period to establish both intra- and interrater
      reliability. RESULTS: One rater demonstrated poor intrarater reliability; a
      second rater failed all students. Kappa statistics improved from the moderate to
      substantial agreement range with the exclusion of the two outlier raters' scores.
      CONCLUSION: There may be faculty who, for different reasons, should not be
      included in high-stakes testing evaluations. All faculty are content experts, but
      not all are expert evaluators.

PMID- 29194299
TI  - Academic Support Programs Utilized for Nursing Students at Risk of Academic
      Failure: A Review of the Literature.
AB  - AIM: The purpose of the literature review is to evaluate and discuss the various
      types of academic support programs used for at-risk nursing students to identify
      those that are most effective. BACKGROUND: Nurse educators are concerned about
      students admitted to nursing programs who are unable to successfully complete the
      program. METHOD: To determine the format and efficacy of academic support
      programs, the literature review addressed the identification of at-risk students
      and academic support programs applicable to all student groups. RESULTS: Nurse
      educators need to develop and implement plans to support and retain students in
      order to address the impending nursing shortage. CONCLUSION: Replacing a student
      lost to academic failure is difficult. Although utilized in different manners,
      academic support programs are an effective retention strategy.

PMID- 29194300
TI  - Nursing Living-Learning Communities and Student Retention: A Qualitative Study.
AB  - BACKGROUND: Living-learning communities have been known to promote student
      performance and a sense of collegiality. Most studies on this topic have utilized
      quantitative methods. AIM: This qualitative comparison case study examined
      personal experiences associated with residing in a living-learning community. The
      study was conducted to explore findings associated with promoting student
      retention. A secondary goal was to explore student experiences with mentoring.
      METHOD: Data were collected using taped recordings of live interviews at two
      universities that have nursing-themed housing. The targeted sample size was 14.
      RESULTS: Themes that emerged from the data were mutual support, importance of the
      resident assistant, and self-determination. CONCLUSION: Nursing students enjoy
      themed housing and especially desire the resident assistant to be a nursing
      student.

PMID- 29194301
TI  - Administrator Perspectives of Advantages and Challenges of Employing Part-Time
      Faculty in Nursing Education Programs: Two Sides of the Same Coin.
AB  - AIM: The purpose of this qualitative research was to explore perspectives of
      administrators (n = 581) regarding advantages and challenges of employing part
      time nurse faculty (PTNF) in schools of nursing in the United States. BACKGROUND:
      The nursing faculty shortage has resulted in increased reliance on PTNF who are
      clinical experts but often inexperienced as educators. A broader evidence base is
      necessary to develop effective strategies to support and retain these faculty
      members. METHOD: Deans and directors of schools of nursing were invited to
      complete an online survey with two open-ended questions about the use of PTNF.
      RESULTS: Five themes emerged from the qualitative descriptive analysis: clinical
      practice as primary role, diversity of educational approaches, effects on full
      time faculty role, economic impact, and contracted educator role. Both positive
      and negative aspects of each theme were identified. CONCLUSION: Results of this
      study support specific efforts to provide professional development and support to
      PTNF.

PMID- 29194302
TI  - Clinical Judgment During Simulation: A Comparison of Student and Faculty Scores.
AB  - This study utilized the Lasater Clinical Judgment Rubric (LCJR) to investigate
      the relationship between the student's self-assessment of clinical judgment
      skills and the faculty's assessment during a human patient simulation. The study
      used a quantitative design with baccalaureate nursing students (n = 94) enrolled
      in an adult health course as participants. The data revealed a positive
      correlation between evaluator and student scores on the LCJR. The findings
      support the use of the LCJR in combination with simulation to evaluate nursing
      students' clinical judgment skills and to quantify competency levels.

PMID- 29194304
TI  - Fostering Student Success: Turning Off Practice Assessment Rationales to Improve
      Proctored Assessment Scores.
AB  - Preparing students with opportunities to practice critical thinking skills is
      essential to success on the National Council Licensure Examination. This pilot
      study was conducted to explore the effectiveness of turning off practice
      assessment answers and rationales on a standardized examination. A retrospective
      study compared students' scores when rationales were turned on and turned off.
      Eighty-one percent of the students were able to achieve the benchmark when the
      answers and rationales were turned off as compared to 71 percent when turned on.
      Faculty can utilize these findings to inform remediation strategies.

PMID- 29194303
TI  - The Effect of Autogenic Training on Self-Efficacy, Anxiety, and Performance on
      Nursing Student Simulation.
AB  - The increased anxiety experienced by nursing students during simulations can
      serve as a significant barrier to learning. The use of anxiety-reducing
      techniques such as autogenic training (AT) can mitigate the negative effects of
      anxiety and improve the overall learning experience. The investigators in this
      study sought to understand the effect of AT on student performance and self
      efficacy during simulation experiences. The use of AT was an effective technique
      to decrease anxiety and increase performance among nursing students during
      nursing simulations. Reducing anxiety during simulations can improve the student
      learning experience.

PMID- 29194305
TI  - Impact of a Simulated Clinical Day With Peer Coaching and Deliberate Practice:
      Promoting a Culture of Safety.
AB  - Nursing education is challenged to shift from task-based proficiencies to higher
      level competencies with patient safety as a priority. Using a quasi-experimental
      pretest/posttest design, a simulation-based, peer-coached, deliberate practice
      clinical substitution was implemented to compare nursing students' knowledge,
      skills, and attitudes for promoting safety. Our findings demonstrated improved
      knowledge and skill acquisition in the intervention and control groups. The
      former trended toward improved team communication attitudes and enteral
      medication skill performance. Additional research with larger samples is needed
      to further investigate this innovative strategy.

PMID- 29194306
TI  - An Innovative and Successful Simulation Day.
AB  - This article discusses the development of a creative and innovative plan to
      incorporate independent activities, including skill reviews and scenarios, into a
      single eight-hour day, using small student groups to enhance the learning process
      for pediatric nursing students. The simulation day consists of skills activities
      and pediatric simulation scenarios using the human patient simulator. Using small
      student groups in simulation captures the students' attention and enhances
      motivation to learn. The simulation day is a work in progress; appropriate
      changes are continually being made to improve the simulation experience for
      students.

PMID- 29194307
TI  - Use of Mindful Observer to Extend Simulation Learning Experience.
AB  - Simulation is a teaching strategy that allows students to experience patient care
      situations in a safe environment. After these experiences, students will
      understand and respond more readily when exposed in clinical practice. An
      increase in student enrollment meant incorporating larger numbers of students
      into simulations. Faculty at an associate degree nursing program decided to use
      the observer role. At the time, mindfulness was being integrated throughout the
      curriculum. Use of a mindful observer during simulations resulted in an effective
      learning strategy as reported by students.

PMID- 29194308
TI  - Active Learning Strategies to Enhance Nursing Students' Knowledge of
      Pharmacology.
AB  - This article presents the author's experience using gaming and social media to
      enhance undergraduate nursing students' pharmacology knowledge. Although gaming
      may help with rote learning, active participation in gaming was not associated
      with higher exam or final course grades. Active participation in social media, on
      the other hand, was associated with higher exam and final course grades.

PMID- 29194309
TI  - Care of the Older Adult With Postoperative Delirium: An Interprofessional
      Simulation for Undergraduate Nursing Students.
AB  - Because of the expanding older adult population, undergraduate nursing students
      need to be introduced to the unique challenges of taking care of older adults.
      Using simulation to demonstrate some of these challenges allows these entry-level
      students to learn in a nonthreatening environment. By focusing on an older adult
      patient who is experiencing postoperative delirium in a simulation, students can
      practice not only how to complete a safety assessment but also effective
      communication skills with the patient, family, and members of the
      interprofessional health care team.

PMID- 29194310
TI  - Dual Enrollment Nursing Partnerships: Steps to Successful Implementation.
AB  - This article discusses the planning and implementation of a dual enrollment
      initiative between an associate degree and baccalaureate nursing program. This
      type of endeavor offers an advantage to nursing students by allowing them to
      enroll concurrently in both academic programs, avoiding academic breaks and
      creating a streamlined educational progression toward the BSN degree. Dual
      enrollment programs are a transformational way to meet Institute of Medicine
      recommendations for increasing the number of BSN-prepared nurses while
      strengthening ties between associate degree and baccalaureate nursing programs.

PMID- 29194311
TI  - Augmented Intelligence and Nursing.

PMID- 29194312
TI  - The NLN's Certified Nurse Educator (CNE) Program Has Surpassed 5,000 and Gone
      Global.

PMID- 29194313
TI  - A Crisis in Competency: The Strategic and Ethical Imperative to Assessing New
      Graduate Nurses' Clinical Reasoning.

PMID- 29194314
TI  - Preliminary results of a novel hay-hole fall prevention initiative.
AB  - BACKGROUND: Hay-hole falls are a prevalent source of trauma among Anabaptists
      particularly Anabaptist youth. We sought to decrease hay-hole falls in South
      Central Pennsylvania through the development and distribution of all-weather hay
      hole covers to members of the at-risk Anabaptist community. METHODS: Following
      the creation of a rural trauma prevention syndicate, hay-hole cover prototypes co
      designed and endorsed by the Pennsylvania Amish Safety Committee were developed
      and distributed throughout South Central Pennsylvania. Preintervention and
      postintervention surveys were distributed to recipients to gain an understanding
      of the hay-hole fall problem in this population, to provide insight into the
      acceptance of the cover within the community, and to determine the efficacy of
      the cover in preventing falls. RESULTS: A total of 231 hay-hole covers were
      distributed throughout eight rural trauma-prone counties in Pennsylvania.
      According to preintervention survey data, 52% of cover recipients reported at
      least one hay-hole fall on their property, with 46% reporting multiple falls
      (median fall rate, 1.00 [1.00-2.00] hay-hole falls per respondent). The median
      self-reported distance from hay-hole to ground floor was 10.0 (8.00-12.0) feet,
      and the median number of hay-holes present on-property was 3.00 (2.00-4.00) per
      respondent. Postintervention survey data found 98% compliance with hay-hole cover
      installation and no subsequent reported hay-hole falls. CONCLUSION: With the
      support of the Pennsylvania Amish Safety Committee, we developed a well-received
      hay-hole cover which could effectively reduce fall trauma across other rural
      communities in the United States. LEVEL OF EVIDENCE: Epidemiological study, Level
      III.

PMID- 29194315
TI  - Hereditary thrombophilia in trauma patients with venous thromboembolism: Is
      routine screening necessary?
AB  - BACKGROUND: Venous thromboembolism (VTE), including deep venous thrombosis (DVT)
      and pulmonary embolism (PE), remains a common complication following trauma. The
      role of hereditary thrombophilia (HT) in posttraumatic VTE is unknown. In the
      general population with a first-time DVT, Factor V Leiden (FVL) and prothrombin
      G20210A mutation (PGM) are the most common types of HT with an incidence of 20%
      to 25% and 6% to 18%, respectively. The objective of this study was to identify
      the incidence of FVL and PGM in posttraumatic VTE to determine whether routine
      screening for HT in trauma should be performed. METHODS: We conducted a
      prospective observational study at our Level I trauma center from 2013 to 2016
      when 70 patients with posttraumatic DVT and PE were screened for FVL and PGM.
      Demographics, injury characteristics, and established risk factors for VTE were
      collected for each patient. Statistical analysis was performed to compare
      patients with and without HT. RESULTS: The incidence of FVL and PGM in
      posttraumatic VTE was 1.4% and 5.7%, respectively. All HT-positive patients had a
      DVT and one had an associated PE. Both the individual risk factors and the total
      number of risk factors for VTE were similar between the HT-positive group and the
      HT-negative group. CONCLUSION: There was a lower incidence of FVL and PGM in
      patients with posttraumatic DVT than in patients with a first-time DVT in the
      general population. HT does not appear to significantly contribute to
      posttraumatic VTE in our trauma population. Further research is warranted to
      determine whether routine screening for HT in trauma should be performed. LEVEL
      OF EVIDENCE: Epidemiological study, level III; Care management/therapeutic study,
      level IV.

PMID- 29194317
TI  - Gut epithelial cell-derived exosomes trigger posttrauma immune dysfunction.
AB  - BACKGROUND: Exosomes are extracellular vesicles that act as endogenous mediators
      of the immune response. We have previously shown that exosomes released into
      mesenteric lymph (ML) following trauma (T)/hemorrhagic shock (HS) induce
      proinflammatory cytokine production in macrophages and are involved in the
      pathogenesis of postshock acute lung injury. However, the cellular origin of ML
      exosomes and their role in the posttrauma immune response remains unclear. We
      hypothesized that exosomes released from damaged-intestinal epithelial cells
      contribute to posttrauma immune dysfunction by altering the function of dendritic
      cells (DCs), key regulators of the adaptive immunity. METHODS: Male rats
      underwent cannulation of the femoral artery, jugular vein and ML duct. T/HS was
      induced by laparotomy and 60 minutes of hemorrhagic shock followed by
      resuscitation. The ML was collected before (preshock) and after T/HS (post-T/HS)
      for isolation of exosomes. Surface epitopes of exosomes isolated from ML were
      assessed by flow cytometry to determine their cellular origin and phenotypic
      changes. The immunomodulatory effects of ML exosomes on DCs were assessed by
      Annexin V apoptosis assay, expression of costimulatory molecules, and antigen
      presenting capacity to lymphocytes. RESULTS: Exosomes isolated from ML highly
      expressed CD63 (exosome marker) and epithelial cell-specific marker, suggesting
      their derivation from intestinal epithelial cells. The expression of
      immunomodulatory molecules, such as major histocompatibility complex class II and
      Fas ligand on ML exosomes, was significantly increased after T/HS. Coincubation
      of DCs with exosomes isolated from ML after T/HS increased DC apoptosis twofold
      compared with preshock ML exosomes. Furthermore, post-T/HS ML exosomes
      significantly suppressed lipopolysaccharide-mediated expression of CD80 and CD86
      on DCs as well as decreased their antigen-presenting capacity to induce
      lymphocytes proliferation. CONCLUSION: Gut epithelial cells release
      immunomodulatory exosomes into the ML after T/HS and resuscitation. Mesenteric
      lymph exosomes may be critical mediators of posttraumatic immunosuppression
      causing depletion and dysfunction of DCs.

PMID- 29194316
TI  - Tubastatin A prevents hemorrhage-induced endothelial barrier dysfunction.
AB  - BACKGROUND: Microvascular hyperpermeability resulting from endothelial barrier
      dysfunction (EBD) is associated with worse clinical outcomes in trauma-induced
      hemorrhagic shock. We have previously shown that treatment with Tubastatin A
      (TubA), a histone deacetylase 6 inhibitor, improves outcomes in animal models of
      shock. In this study, we investigate whether TubA treatment may prevent trauma
      related EBD. METHODS: Wistar-Kyoto rats subjected to 40% hemorrhage were treated
      with TubA or vehicle control. Acute lung injury (ALI) was assessed histologically
      from tissues harvested 6 hours posthemorrhage. In vitro, human umbilical vein
      endothelial cells (HUVECs) were cultured in EGM BulletKit medium. Medium was
      exchanged for glucose-free Dulbecco's Modified Eagle Medium (0.5% fetal bovine
      serum) with or without TubA, and cells were placed in an anoxic chamber (5% CO2,
      95% N2, 20-48 hours). Expression of acetylated tubulin and hypoxia-inducible
      factor 1alpha was measured by Western blot. Soluble Intercellular Adhesion
      Molecule-1 concentration within the medium, a marker of endothelial integrity,
      was determined using enzyme-linked immunosorbent assay. Monolayers were assessed
      for permeability via transwell assays using fluorescein isothiocyanate-labeled
      albumin. RESULTS: Rats treated with TubA had significantly reduced ALI relative
      to vehicle control. In vitro, TubA significantly attenuated anoxia-induced
      hyperpermeability, hypoxia-inducible factor 1alpha expression, and glycocalyx
      shedding. CONCLUSIONS: Our findings demonstrate that TubA prevents hemorrhage
      induced ALI in rats. Additionally, we have shown that TubA prevents anoxia
      induced EBD in vitro. Taken together, these results suggest that TubA could
      attenuate microvascular hyperpermeability related to hemorrhagic shock.

PMID- 29194318
TI  - Non-compliance with ACS-COT recommended criteria for full trauma team activation
      is associated with undertriage deaths.
AB  - BACKGROUND: The appropriate triage of acutely injured patients within a trauma
      system is associated with improved rates of mortality and optimal resource
      utilization. The American College of Surgeons Committee on Trauma (ACS-COT) put
      forward six minimum criteria (ACS-6) for full trauma team activation (TTA). We
      hypothesized that ACS-COT verified trauma center compliance with these criteria
      is associated with low under-triage rates and improved overall mortality.
      METHODS: Data from a state-wide collaborative quality initiative was utilized. We
      used data collected from 2014 through 2016 at 29 ACS verified level 1 and 2
      trauma centers. Inclusion criteria were: adult patients (>=16 years) and ISS >=5.
      Quantitative data existed to analyze four of the ACS-6 criteria (ED SBP<=90 mmHg,
      respiratory compromise/intubation, central GSW, and GCS<9). Patients were
      considered to be under-triaged if they had major trauma (ISS>15) and did not
      receive a full TTA. RESULTS: 51,792 patients were included in the study.
      Compliance with ACS-6 minimum criteria for full TTA varied from 51% to 82%.
      Presence of any ACS-6 criteria was associated with a high intervention rate and
      significant risk of mortality (OR 16.7, 95% CI 15.2-18.3, p<0.001). Of the 1004
      deaths that were not a full activation, 433 (43%) were classified as under
      triaged, and 301 (30%) had at least one ACS-6 criteria present. Under-triaged
      patients with any ACS-6 criteria were more likely to die than those who were not
      under-triaged (30% vs 21%, p=0.001). GCS<9 and need for emergent intubation were
      the ACS-6 criteria most frequently associated with under-triage mortality.
      CONCLUSIONS: Compliance with ACS-COT minimum criteria for full TTA remains sub
      optimal and undertriage is associated with increased mortality. This data
      suggests that the most efficient quality improvement measure around triage should
      be ensuring compliance with the ACS-6 criteria. This study suggests that practice
      pattern modification to more strictly adhere to the minimum ACS-COT criteria for
      full TTA will save lives. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria, Level
      III.

PMID- 29194319
TI  - Variations in outcomes of emergency general surgery patients across hospitals: A
      call to establish emergency general surgery quality improvement program.
AB  - BACKGROUND: National Surgical Quality Improvement Program and Trauma Quality
      Improvement Program have shown variations in risk-adjusted outcomes across
      hospitals. Our study hypothesis was that there would be similar variation in risk
      adjusted outcomes of emergency general surgery (EGS) patients. METHODS: We
      undertook a retrospective analysis of the National Inpatient Sample database for
      2010. Patients with EGS diseases were identified using American Association for
      the Surgery of Trauma definitions. A hierarchical logistic regression model was
      used to model in-hospital mortality, accounting for patient characteristics,
      including age, sex, race, ethnicity, insurance type, and comorbidities. Predicted
      to-expected mortality ratios with 90% confidence intervals were used to identify
      hospitals as low mortality (ratio significantly lower than 1), high mortality
      (ratio significantly higher than 1), or average mortality (ratio overlapping 1).
      RESULTS: Nationwide, 2,640,725 patients with EGS diseases were treated at 943
      hospitals in 2010. About one-sixth of the hospitals (139, 15%) were low
      mortality, a quarter were high mortality (221, 23%), and the rest were average
      mortality. Mortality ratio at low mortality hospitals was almost four times lower
      than that of high mortality hospitals (0.57 vs. 2.03, p < 0.0001). If high and
      average mortality hospitals performed at the same level as low mortality
      hospitals, we estimate 16,812 (55%) more deaths than expected. CONCLUSION: There
      are significant variations in risk-adjusted outcomes of EGS patients across
      hospitals, with several thousand higher than expected number of deaths
      nationwide. Based on the success of National Surgical Quality Improvement Program
      and Trauma Quality Improvement Program, we recommend establishing EGS quality
      improvement program for risk-adjusted benchmarking of hospitals for EGS patients.
      LEVEL OF EVIDENCE: Care management, level III.

PMID- 29194320
TI  - No intravenous access, no problem: Intraosseous administration of tranexamic acid
      is as effective as intravenous in a porcine hemorrhage model.
AB  - BACKGROUND: The acute coagulopathy of trauma is often accompanied by
      hyperfibrinolysis. Tranexamic acid (TXA) can reverse this phenomenon, and, when
      given early, decreases mortality from bleeding. Establishing intravenous (IV)
      access can be difficult in trauma and intraosseous (IO) access is often preferred
      for drug administration. Currently, there are no data on the efficacy of IO
      administered TXA. Our objectives were to compare serum concentrations of TXA when
      given IV and IO and to compare the efficacy of IO administered TXA to IV at
      reversing hyperfibrinolysis. METHODS: Using a porcine hemorrhage and ischemia
      reperfusion model, 18 swine underwent hemorrhagic shock followed by a tissue
      plasminogen activator infusion to induce hyperfibrinolysis. Animals then received
      an IV or tibial IO infusion of TXA over 10 minutes. Blood was then analyzed using
      rotational thromboelastometry to monitor reversal of hyperfibrinolysis. Serum was
      analyzed for drug concentrations. RESULTS: After hemorrhage and ischemia
      reperfusion, there were no significant differences in mean arterial pressure (48
      vs. 49.5), lactate (11.1 vs. 10.8), and pH (7.20 vs. 7.22) between groups.
      Intraosseous TXA corrected the lysis index at 30 minutes in EX-TEM and IN-TEM,
      like IV infusion. Peak serum levels of TXA after IV and IO administration show
      concentrations of 160.9 MUg/mL and 132.57 MUg/mL respectively (p = 0.053). Peak
      levels occurred at the completion of infusion. Drug levels were tracked for four
      hours. At the end of monitoring, plasma concentrations of TXA were equivalent.
      CONCLUSION: Intraosseous administration of TXA is as effective as IV in reversing
      hyperfibrinolysis in a porcine model of hemorrhagic shock. Intraosseous
      administration was associated with a similar peak levels, pharmacokinetics, and
      clearance. Intraosseous administration of TXA can be considered in hemorrhagic
      shock when IV access cannot be established.

PMID- 29194321
TI  - Variability in management of blunt liver trauma and contribution of level of
      American College of Surgeons Committee on Trauma verification status on
      mortality.
AB  - BACKGROUND: Patients who sustain blunt liver trauma and are treated at an
      American College of Surgeons Committee on Trauma-verified Level I trauma center
      have an overall lower risk of mortality compared with patients admitted to a
      level II trauma center. However, elements contributing to these differences are
      unknown. We hypothesize that practice variation exists between trauma centers in
      management of blunt liver injury. Our objective is to identify practice
      variations and their effect on clinical outcomes. METHODS: Data from a statewide
      collaborative quality initiative for trauma were used. The data set contains
      information from 29 American College of Surgeons Committee on Trauma verified
      Levels I and II trauma centers from 2011 to 2016. Propensity score matching was
      used to create cohorts of patients treated at Levels I or II trauma centers. The
      1:1 matched cohorts were used to compare in-hospital mortality, management
      strategy, complications, intensive care unit (ICU) and hospital length of stay,
      and failure to rescue. RESULTS: Four hundred fifty-four patients with grade 3 or
      higher blunt liver injury were included. Patients treated at level II trauma
      centers had higher in-hospital mortality than those treated at Level I trauma
      centers (15.4% vs 8.8%, p = 0.03). Level II trauma centers used angiography less
      compared with Level I centers (p = 0.007) and admitted significantly fewer
      patients to the ICU (p = 0.002). The ICU status was associated with reduced
      mortality (7.2% vs 23.9%, p < 0.001). Despite a lower rate of overall
      complications, Level II trauma centers were more likely to fail in rescuing their
      patients (p = 0.045). CONCLUSION: Admission with a high-grade liver injury to a
      Level II trauma center is associated with increased in-hospital mortality. Level
      II trauma centers were less likely to use angiography or admit high-grade liver
      injuries to the ICU. This variation in practice may lead to the inability to
      rescue critically ill patients. Future research should investigate contributors
      to underutilization of resources for patients with high-grade liver injuries.
      LEVEL OF EVIDENCE: Care management, level IV.

PMID- 29194322
TI  - Direct peritoneal resuscitation reduces intestinal permeability after brain
      death.
AB  - BACKGROUND: The profound inflammatory response associated with brain death is
      frequently cited as the reason organs procured from brain dead donors are
      associated with worse graft function. The intestine releases inflammatory
      mediators in other types of shock, but its role is brain death has not been well
      studied. Direct peritoneal resuscitation (DPR) improves visceral organ blood flow
      and reduces inflammation after hemorrhagic shock. We hypothesized that use of DPR
      would maintain intestinal integrity and reduce circulating inflammatory mediators
      after brain death. METHODS: Brain death was induced in male Sprague-Dawley rats
      by inserting a 4F Fogarty catheter into the epidural space and slowly inflating
      it. After herniation, rats were resuscitated with normal saline to maintain a
      mean arterial pressure of 80 mm Hg and killed with tissue collected immediately
      (time 0), or 2 hours, 4 hours, or 6 hours after brain death. Randomly selected
      animals received DPR via an intraperitoneal injection of 30-mL commercial
      peritoneal dialysis solution. RESULTS: Levels of proinflammatory cytokines,
      including IL-1beta and IL-6, as well as high-mobility group box 1 protein and
      heat shock protein 70, were all increased after brain death and decreased with
      DPR. Fatty acid binding protein and lipopolysaccharide, both markers of
      intestinal injury, were increased in the serum after brain death and decreased
      with DPR. Immunohistochemistry staining for zona occludin-1 showed decreased
      intestinal tight junction integrity after brain death, which improved with DPR.
      CONCLUSIONS: Intestinal permeability increases after brain death, and this
      contributes to the increased inflammation seen throughout the body. Using DPR
      prevents intestinal ischemia and helps preserve intestinal integrity. This
      suggests that using this novel therapy as an adjunct to the resuscitation of
      brain dead donors has the potential to reduce inflammation and potentially
      improve the quality of transplanted organs.

PMID- 29194323
TI  - Unconscious cognitive dysfunction in emotion dysregulation and psychopathology of
      panic disorder: evidence from the late positive potential.

PMID- 29194325
TI  - TO THE EDITOR.

PMID- 29194326
TI  - From the Editor.

PMID- 29194327
TI  - Guest Editorial.

PMID- 29194328
TI  - The Power of the Frame: Systems Transformation Framework for Health Care Leaders.
AB  - Health care leaders are responsible for oversight of multiple and competing
      change interventions. These interventions regularly fail to achieve the desired
      outcomes and/or sustainable results. This often occurs because of the mental
      models and approaches that are used to plan, design, implement, and evaluate the
      system. These do not account for inherent characteristics that determine the
      system's likely ability to innovate while maintaining operational effectiveness.
      Theories exist on how to assess a system's readiness to change, but the
      definitions, constructs, and assessments are diverse and often look at facets of
      systems in isolation. The Systems Transformation Framework prescriptively defines
      and characterizes system domains on the basis of complex adaptive systems theory
      so that domains can be assessed in tandem. As a result, strengths and challenges
      to implementation are recognized before implementation begins. The Systems
      Transformation Framework defines 8 major domains: vision, leadership,
      organizational culture, organizational behavior, organizational structure,
      performance measurements, internal learning, and external learning. Each domain
      has principles that are critical for creating the conditions that lead to
      successful organizational adaptation and change. The Systems Transformation
      Framework can serve as a guide for health care leaders at all levels of the
      organization to (1) create environments that are change ready and (2) plan,
      design, implement, and evaluate change within complex adaptive systems.

PMID- 29194329
TI  - Buildings, Barriers, and Breakthroughs: Bridging Gaps in the Health Care
      Enterprise.
AB  - Health care architecture and design are critical resources that are often
      underestimated and overlooked. As we seek to extract every available resource at
      our disposal to serve patients and sustain the bottom line, it is vital that we
      consider the influence the building imposes on the patient and caregiver
      experiences. Buildings impact both caregiver behaviors and the economic
      enterprise and are, therefore, the business of health care executives. This
      understanding is not only an executive obligation, it is an executive
      opportunity. Furthermore, the built environment can be a source for innovation in
      an industry whose future depends on nurse leaders to champion ingenuity with
      simplicity and relevance. Nurse leaders are ideally positioned to bridge health
      care building design and best practice.

PMID- 29194330
TI  - Accelerating Innovation Through Coopetition: The Innovation Learning Network
      Experience.
AB  - Coopetition, the simultaneous pursuit of cooperation and competition, is a
      growing force in the innovation landscape. For some organizations, the primary
      mode of innovation continues to be deeply secretive and highly competitive, but
      for others, a new style of shared challenges, shared purpose, and shared
      development has become a superior, more efficient way of working to accelerate
      innovation capabilities and capacity. Over the last 2 decades, the literature
      base devoted to coopetition has gradually expanded. However, the field is still
      in its infancy. The majority of coopetition research is qualitative, primarily
      consisting of case studies. Few studies have addressed the nonprofit sector or
      service industries such as health care. The authors believe that this article may
      offer a unique perspective on coopetition in the context of a US-based national
      health care learning alliance designed to accelerate innovation, the Innovation
      Learning Network or ILN. The mission of the ILN is to "Share the joy and pain of
      innovation," accelerating innovation by sharing solutions, teaching techniques,
      and cultivating friendships. These 3 pillars (sharing, teaching, and cultivating)
      form the foundation for coopetition within the ILN. Through the lens of
      coopetition, we examine the experience of the ILN over the last 10 years and
      provide case examples that illustrate the benefits and challenges of coopetition
      in accelerating innovation in health care.

PMID- 29194331
TI  - Kaiser's School of Nursing: A 70-Year Legacy of Disruptive Innovation.
AB  - A legacy project was launched in 2016 to research, capture, and record the
      history and voice of Kaiser Foundation School of Nursing alumni. The
      inspirational stories of these early nursing pioneers emerged within a disruptive
      and innovative health care system known as Kaiser Permanente. Led by a doctorally
      prepared nurse director, the new school boldly rejected the dominant social norms
      of the 1940s by welcoming minorities and offering an unprecedented curriculum
      that prioritized prevention, health promotion, and wellness over conventional
      institutionalized sick care models. Kaiser Foundation School of Nursing alumni
      became Kaiser Permanente's earliest nurse leaders, educators, and care advocates.
      They helped revolutionize the key concepts of integrated patient care. As early
      innovators, many graduates pursued advanced degrees and were instrumental in
      defining expanded nursing roles, including the introduction of nurse
      practitioners in California. How Kaiser Foundation School of Nursing transcended
      the traditions and cultural norms of the day offers a reflective narrative on the
      enduring leadership attributes of disruptive innovation and the nurse executive's
      role in reimagining care for future generations.

PMID- 29194332
TI  - Operationalizing a Nursing Innovation Center Within a Health Care System.
AB  - In nursing, the terms "innovation" and "innovative" are used freely, especially
      when individuals or groups either develop something new or improve upon current
      practice. Innovation is often considered adjunct work, not part of foundational
      work that aims to meet the vision, mission, and values of the organization. Nurse
      leaders must include innovation as an important theme of this foundational work.
      Innovation must become a core expectation of all nurses and nursing team members.
      Team members can provide ideas that lead to innovations. They can also carry out
      roles that enhance or cultivate ideas, promote prototyping, ensure innovative
      ideas are efficacious and effective, and facilitate dissemination and diffusion
      into practice. To ensure that innovation is incorporated as part of nursing
      practice and then sustained over time, horizontal (elemental) and vertical
      (global) infrastructure and processes are needed. In this article,
      operationalization of a Nursing Innovation Center is described and rationale for
      specific horizontal and vertical services and features is discussed.

PMID- 29194333
TI  - Nursing Integration and Innovation Across a Multisystem Enterprise: Priorities
      for Nurse Leaders.
AB  - There is no escaping the fact that the ability to skillfully influence change is
      a requirement for nurse leaders. This need is intensified as the national health
      care system reforms and as the morphology of health care systems continues to
      change, especially in academic health care systems. The purpose of this article
      was 2-fold. The first objective was to relay the experience of the integration of
      nursing practice, education, and research within an academic health care system.
      The second was to, through this story of integration, expose the uniqueness and
      importance of nurse leader roles influencing innovation across a multisystem
      enterprise to fulfill the organization's mission.

PMID- 29194334
TI  - Creativity and Innovation in Health Care: Tapping Into Organizational Enablers
      Through Human-Centered Design.
AB  - There is an increasing drive in health care for creativity and innovation to
      tackle key health challenges, improve quality and access, and reduce harm and
      costs. Human-centered design (HCD) is a potential approach to achieving
      organizational innovation. However, research suggests the nursing workforce feels
      unsupported to take the risks needed for innovation, and leaders may not
      understand the conditions required to fully support them. The aim of this study
      was to identify enabling conditions that support frontline nurses in their
      attempts to behave as champions of innovation and change. An HCD workshop was
      undertaken with 125 nurses employed in clinical practice at Kaiser Permanente.
      The workshop included empathy mapping and semistructured questions that probed
      participant experiences with innovation and change. The data were collated and
      thematic analysis undertaken through a Grounded Theory approach. The data were
      analyzed to identify key enabling conditions. Seven enablers emerged: personal
      need for a solution; challenges that have meaningful purpose; clarity of goal and
      control of resources; active experimentation; experiences indicating progress;
      positive encouragement and confidence; and provision of psychological safety.
      These enablers were then translated into pragmatic guidelines for leaders on how
      the tools of HCD may be leveraged for innovation and change in health care.

PMID- 29194335
TI  - The CNO and Leading Innovation: Competencies for the Future.
AB  - Although innovation is critical to success in today's tumultuous environment,
      health care is slow to embrace it, and there is significant variability in
      strategic adoption of innovation across organizations. Nurse leaders do not need
      to be innovators themselves but must engage in, and have the ability to create,
      an organizational culture of innovation. Twenty-six leadership behaviors specific
      to innovation leadership were identified through a Delphi study to develop
      competencies as well as the knowledge, skills, and attitudes that support nurse
      leaders in acquiring or expanding the capability of nurse leaders to create a
      culture of innovation. It was demonstrated that nursing innovation experts were
      able to differentiate between general leadership behaviors and innovation leader
      behaviors. In addition, the need to acquire basic leadership competencies before
      mastering innovation leader competencies was identified. Five strategies to
      initiate or expand a culture of innovation in organizations were identified,
      including (1) assessment of organizational capacity for innovation; (2)
      acknowledgement of the responsibility of all leaders to create an innovation-rich
      environment; (3) provision of education, skill building, and coaching; (4)
      encouragement of an ongoing practice of innovation, even in the face of failure;
      and (5) development of a sustainable culture of innovation.

PMID- 29194336
TI  - International Nursing: Constructing an Advanced Practice Registered Nurse
      Practice Model in the UAE: Using Innovation to Address Cultural Implications and
      Challenges in an International Enterprise.
AB  - Despite utilization of the advanced practice registered nurse (APRN) in the
      United States health care system, there is little information about the
      introduction, utilization, and challenges of the APRN role globally, especially
      in the Middle East. This article will look at how one hospital in the United Arab
      Emirates introduced the APRN role to a health care environment of a country where
      it has not been recognized historically. Cultural challenges and barriers for the
      implementation of the role include regulatory, societal, and institutional.
      Innovation and collaboration are necessary to address these challenges and
      barriers and to pave the way for a successful advanced practice model pilot, as
      well as for the future use of the role. Innovation is also one of the key
      performance indicators for the country's health care. However, the idea of
      advanced practice is a new concept that has been outside the mainstream health
      care practice for the United Arab Emirates. To help with the implementation, a
      road map was developed to outline the steps necessary to provide a safe practice
      environment. The plan included aligning with the ministry of health nursing and
      midwifery council, as well as the Health Authority of Abu Dhabi, to help them
      learn more about the US model of advanced practice, along with benefits, and
      outcomes of the role. Developing the role of the APRN will benefit the future
      state of the health care infrastructure for not only the United Arab Emirates but
      throughout the Middle East.

PMID- 29194337
TI  - NCH Healthcare System, Naples, Florida: Philanthropy Targeted for Nursing
      Innovation.

PMID- 29194338
TI  - Nurses' Use of Positive Deviance When Encountering Electronic Health Records
      Related Unintended Consequences.
AB  - As organizations adopt electronic health records (EHRs), nurses frequently
      encounter system barriers and difficulty performing role expectations. This
      article describes nurses' experiences with unintended consequences emerging from
      the use of an EHR. In some situations, nurses were positively deviant when
      encountering unintended consequences relating to EHRs to accomplish patient care
      or protect patient safety. Nurses engaged in work-arounds to provide patient care
      when the EHR did not meet their needs, sometimes in positively deviant ways.
      Qualitative data were collected from 5 open-ended questions at the end of a
      quantitative survey. Analysis included coding of responses and organization of
      processes in line with the triangle model, a human factors framework, to identify
      overarching themes. Five themes emerged: (1) User support after implementation of
      EHR; (2) User satisfaction with EHR; (3) Communication for patient care, quality,
      and safety; (4) Effort to complete tasks; and (5) Areas for improvement. Nurses'
      ability to adopt positive deviance as they experience unintended consequences
      offers opportunities for organizations to engage nursing perspectives in
      improving the EHR and engineer it to be more resilient to nursing work.

PMID- 29194340
TI  - Heat Shock Factor 1 Inhibits the Expression of Suppressor of Cytokine Signaling 3
      in Cerulein-Induced Acute Pancreatitis.
AB  - BACKGROUND: Heat shock factor 1 (HSF1), an important transcriptional molecule in
      the heat shock process, can regulate the expression of a lot of inflammatory
      mediators in addition to heat shock proteins. This study evaluated the inhibitive
      function of HSF1 on the expression of suppressor of cytokine signaling 3 in
      cerulein-induced acute pancreatitis. METHODS: After HSF1 mice, HSF1 mice, and
      AR42J cells were treated with cerulein, histopathological score, expression of
      SOCS3 mRNA, and protein levels were analyzed by using RT-PCR, quantitative real
      time RT-PCR, and western blotting, respectively. DNA binding and transcription
      activity of HSF1 to the SOCS3 promoter were detected by chromatin
      immunoprecipitation and luciferase reporter assays. RESULTS: The
      histopathological scores of the pancreas decreased significantly in the cerulein
      induced HSF1 mice compared with the cerulein-induced HSF1 mice. SOCS3 mRNA and
      protein level decreased in the pancreas of the unstimulated HSF1 and HSF1 mice,
      whereas increased in the pancreas of the cerulein-induced HSF1 and HSF1 mice,
      with higher in the pancreas of cerulein-induced HSF1mice. In the pcDNA3.1
      transfected AR42J cells, SOCS3 protein decreased and was upregulated after the
      cerulein stimulation, whereas HSF1 overexpression inhibited the upregulation. In
      the scramble-transfected AR42J cells, SOCS3 protein decreased and was upregulated
      after the cerulein stimulation, whereas HSF1-RNAi further promoted the
      upregulation. EMSA and chromatin immunoprecipition showed that HSF1 could
      directly bind to SOCS3 promoter region. Reporter assays showed that HSF1 could
      inhibit the transcriptional activity on SOCS3 promoter. CONCLUSIONS: HSF1 can
      protect AR42J cells from cerulein-induced pancreatitis through inhibiting the
      expression of SOCS3.

PMID- 29194339
TI  - Risk Factors for the Development of Acute Respiratory Distress Syndrome Following
      Hemorrhage.
AB  - BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR)
      study evaluated the effects of plasma and platelets on hemostasis and mortality
      after hemorrhage. The pulmonary consequences of resuscitation strategies that
      mimic whole blood, remain unknown. METHODS: A secondary analysis of the PROPPR
      study was performed. Injured patients predicted to receive a massive transfusion
      were randomized to 1:1:1 versus 1:1:2 plasma-platelet-red blood cell ratios at 12
      Level I North American trauma centers. Patients with survival >24 h, an intensive
      care unit (ICU) stay, and a recorded PaO2/FiO2 (P/F) ratio were included. Acute
      respiratory distress syndrome (ARDS) was defined as a P/F ratio < 200, with
      bilateral pulmonary infiltrates, and adjudicated by investigators. RESULTS: Four
      hundred fifty-four patients were reviewed (230 received 1:1:1, 224 1:1:2). Age,
      sex, injury mechanism, and regional abbreviated injury scale (AIS) scores did not
      differ between cohorts. Tidal volume, positive end-expiratory pressure, and
      lowest P/F ratio did not differ. No significant differences in ARDS rates (14.8%
      vs. 18.4%), ventilator-free (24 vs. 24) or ICU-free days (17.5 vs. 18), hospital
      length of stay (22 days vs. 18 days), or 30-day mortality were found (28% vs.
      28%). ARDS was associated with blunt injury (OR 3.61 [1.53-8.81] P < 0.01) and
      increasing chest AIS (OR 1.40 [1.15-1.71] P < 0.01). Each 500 mL of crystalloid
      infused during hours 0 to 6 was associated with a 9% increase in the rate of ARDS
      (OR 1.09 [1.04-1.14] P < 0.01). Blood given at 0 to 6 or 7 to 24 h were not risk
      factors for lung injury. CONCLUSION: Acute crystalloid exposure, but not blood
      products, is a potentially modifiable risk factor for the prevention of ARDS
      following hemorrhage.

PMID- 29194341
TI  - Applying Positive End-Expiratory Pressure During Mechanical Ventilation Causes
      Pulmonary Redox Imbalance and Inflammation in Rats.
AB  - BACKGROUND: Mechanical ventilation (MV) may induce or aggravate lung injury
      through the production of cytokines, inflammatory infiltration of neutrophils,
      and changes in the permeability of the alveolar-capillary barrier. The use of
      positive end-expiratory pressure (PEEP) helps improve gas exchanges avoiding
      alveolar collapse at the end of expiration. The present study aimed to analyze
      inflammatory response and redox imbalance in lungs of rats submitted to MV with
      and without PEEP. METHODS: Eighteen Wistar rats were divided into three groups:
      control (CG), PEEP group (PG), and zero PEEP (ZEEP) group (ZG). PG and ZG were
      submitted to MV for 60 min with or without PEEP, respectively. Subsequently, the
      animals were euthanized, and blood, bronchoalveolar lavage fluid, and lungs were
      collected for analyses. RESULTS: The number of neutrophils was higher in PG
      compared with CG. Leucocyte and neutrophil influx in bronchoalveolar lavage fluid
      was higher in PG compared with CG. PG showed an increase in alveolar area
      compared with the other groups. There were increases in the levels of chemokines,
      CCL3 and CCL5, in PG compared with CG. There were increases in oxidation of
      lipids and proteins in PG compared with other groups. There were increases in the
      activity of superoxide dismutase and catalase in PG compared with CG and ZG.
      However, there was a decrease in the ratio of glutathione to glutathione
      disulfide in PG compared with other groups. CONCLUSIONS: MV with PEEP caused
      redox imbalance and inflammation in lungs of healthy rats.

PMID- 29194342
TI  - Tim-3 Regulates Tregs' Ability to Resolve the Inflammation and Proliferation of
      Acute Lung Injury by Modulating Macrophages Polarization.
AB  - We recently reported that CD4CD25 regulatory T cells (Tregs) contributed to the
      recovery of patients with acute lung injury (ALI) by upregulating T cell
      immunoglobulin and mucin-domain containing-3 (Tim-3). However, the molecular
      mechanism by which Tim-3 regulates Tregs' function in the resolution and
      fibroproliferation after ALI remains unknown. In this study, we adoptively
      transferred Tim-3Tregs or Tim-3Tregs into lipopolysaccharide -induced ALI mice
      model. Data demonstrated that Tim-3Tregs not only decreased indices of lung
      inflammation and injury but also mitigated lung fibrosis after ALI. Furthermore,
      we observed that the transfer of Tim-3Tregs led to M2-like macrophage
      differentiation as demonstrated by significantly upregulated levels of M2
      associated phenotypic markers as well as downregulated expressions of M1-related
      markers in both the profibrotic lung tissue and sorted pulmonary monocytes after
      ALI. In addition, cytokines such as interleukin (IL)-10 and IL-4 were also
      upregulated in lung tissues after Tim-3Tregs transferring. In vitro experiments
      further demonstrated that cell-contact cocultures with Tregs lacking Tim-3
      presented decreased polarization of M2-like macrophages partially mediated by a
      decreased expression and function of STAT-3. Therefore, these data demonstrate a
      previously unrecognized function of Tim-3 on Tregs in their ability to repress
      the fibroproliferation of ALI by inducing alternative macrophages polarization.
      Moreover, the data highlight that Tim-3Tregs-mediated induction of M2-like
      macrophages may be a novel treatment modality with transitional potential.

PMID- 29194343
TI  - Blood Mixing Upregulates Platelet Membrane-Bound CD40 Ligand Expression In Vitro
      Independent of Abo Compatibility.
AB  - Platelets play a central role in the inflammation response via CD40 ligand
      (CD40L) expression, which may lead to transfusion reactions. The precise role of
      platelet CD40L-mediated inflammation in transfusion reactions is unclear.
      Therefore, we assessed the effects of in vitro blood mixing on platelet CD40L
      expression. In addition, we examined the effect of ABO compatibility on CD40L
      expression. Donor-packed red blood cells were acquired from a blood bank, and
      recipient blood was obtained from patients undergoing cardiac surgery and
      prepared as washed platelets. Donor blood was mixed with suspended, washed
      recipient platelets to obtain a final mixing ratio of 1%, 5%, or 10% (vol/vol).
      The blood mixtures were divided into three groups: group M, cross-matched blood
      type mixing (n = 20); group S, ABO type-specific uncross-matched blood (n = 20);
      and group I, ABO incompatibility (not ABO type-specific blood and not process
      cross-matched) mixing (n = 20). The blood mixtures were used to detect platelet
      membrane-bound CD40L expression by flow cytometry. Blood mixing resulted in an
      increase in CD40L expression in group M (P < 0.001), group S (P < 0.001), and
      group I (P < 0.001). CD40L expression after blood mixing potentially led to a
      transfusion reaction in each of the groups. There were no differences in CD40L
      expression among the three groups (P = 0.988) correlated with ABO compatibility
      or incompatibility. This indicates that the reactions between red blood cell
      surface antigens and plasma antibodies do not play a role in the induction of
      CD40L expression.

PMID- 29194344
TI  - Direct Peritoneal Resuscitation Alters Leukocyte Infiltration in the Lung After
      Acute Brain Death.
AB  - BACKGROUND: Brain death is associated with significant lung injury and
      inflammation. This has been associated with worse long-term outcomes for
      transplanted lungs. Direct peritoneal resuscitation (DPR) reduces systemic
      inflammation in brain death and improves lung procurement rate. The effect of DPR
      on macrophage and neutrophil infiltration in the lungs is not known. METHODS:
      Male Sprague-Dawley rats had a 4F Fogarty catheter inserted into the skull and
      the balloon inflated until brain death was achieved. Rats were resuscitated with
      normal saline to maintain a mean arterial pressure of 80 mmHg (targeted
      intravenous fluid, TIVF) and DPR animals received an intraperitoneal injection of
      commercial peritoneal dialysis solution. Rats were sacrificed at 0, 2, 4, and 6 h
      after brain death. Protein levels were assessed using quantitative ELISA.
      Leukocytes were quantified using flow cytometry and immunohistochemistry.
      RESULTS: At all time points, DPR downregulated multiple inflammatory cytokines
      including IFN-gamma, TNF-alpha, IL-1alpha, and IL-6. Adhesion molecules ICAM, E
      selectin, and P-selectin were increased above sham at 4 and 6 h after brain death
      and reduced with DPR, whereas VCAM was reduced at 2 and 6 h. Infiltration of
      macrophages and neutrophils were trended downward at 6 h with DPR, though this
      difference was not statistically significant. CONCLUSIONS: Animals that received
      TIVF alone had significant increases in inflammatory cytokines within the lung
      tissue, leading to adhesion molecule expression and ultimately leukocyte
      infiltration. Each stage of inflammation was affected by DPR. Using DPR in brain
      dead organ donors shows promise as a way to reduce lung injury and inflammation.

PMID- 29194345
TI  - Embryonic Ethanol Exposure Affects Early- and Late-Added Cardiac Precursors and
      Produces Long-Lasting Heart Chamber Defects in Zebrafish.
AB  - Drinking mothers expose their fetuses to ethanol, which produces birth defects:
      craniofacial defects, cognitive impairment, sensorimotor disabilities and organ
      deformities, collectively termed as fetal alcohol spectrum disorder (FASD).
      Various congenital heart defects (CHDs) are present in FASD patients, but the
      mechanisms of alcohol-induced cardiogenesis defects are not completely
      understood. This study utilized zebrafish embryos and older larvae to understand
      FASD-associated CHDs. Ethanol-induced cardiac chamber defects initiated during
      embryonic cardiogenesis persisted in later zebrafish life. In addition,
      myocardial damage was recognizable in the ventricle of the larvae that were
      exposed to ethanol during embryogenesis. Our studies of the pathogenesis revealed
      that ethanol exposure delayed differentiation of first and second heart fields
      and reduced the number of early- and late-added cardiomyocytes in the heart.
      Ethanol exposure also reduced the number of endocardial cells. Together, this
      study showed that ethanol-induced heart defects were present in late-stage
      zebrafish larvae. Reduced numbers of cardiomyocytes partly accounts for the
      ethanol-induced zebrafish heart defects.

PMID- 29194346
TI  - Dental Procedures in Primary Health Care of the Brazilian National Health System.
AB  - The aim of this study was to examine the procedures of primary dental health care
      performed by oral health teams (OHTs) adhering to the second cycle of the
      'National Programme for Improving Access and Quality of Primary Care' (PMAQ-AB)
      in Brazil. A cross-sectional descriptive analysis was performed, across 23 dental
      procedures comprising preventive, restorative/prosthetic, surgical, endodontic
      and oral cancer monitoring. Descriptive analysis shows that most of the oral
      health teams carry out basic dental procedures. However, most of the time, they
      do not keep adequate records of suspected cases of oral cancer, diagnosis tests
      or follow-ups, and do not perform dental prosthetic procedures. Data also showed
      disparities in the average number of procedures performed in each Brazilian
      geographical region in 2013-2014, ranging from 13.9 in the northern to 16.5 in
      the southern and south-eastern regions, reinforcing the great social disparities
      between them. Brazilian regions with the highest volume of dental needs deliver
      the lowest number of dental procedures. The need to expand the supply of
      prostheses and the early diagnosis of oral cancer in primary health care (PHC) is
      evident.

PMID- 29194347
TI  - In Vivo and In Vitro Activities and ADME-Tox Profile of a Quinolizidine-Modified
      4-Aminoquinoline: A Potent Anti-P. falciparum and Anti-P. vivax Blood-Stage
      Antimalarial.
AB  - Natural products are a prolific source for the identification of new biologically
      active compounds. In the present work, we studied the in vitro and in vivo
      antimalarial efficacy and ADME-Tox profile of a molecular hybrid (AM1) between 4
      aminoquinoline and a quinolizidine moiety derived from lupinine (Lupinus luteus).
      The aim was to find a compound endowed with the target product profile-1 (TCP-1:
      molecules that clear asexual blood-stage parasitaemia), proposed by the Medicine
      for Malaria Venture to accomplish the goal of malaria elimination/eradication.
      AM1 displayed a very attractive profile in terms of both in vitro and in vivo
      activity. By using standard in vitro antimalarial assays, AM1 showed low
      nanomolar inhibitory activity against chloroquine-sensitive and resistant P.
      falciparum strains (range IC50 16-53 nM), matched with a high potency against P.
      vivax field isolates (Mean IC50 29 nM). Low toxicity and additivity with
      artemisinin derivatives were also demonstrated in vitro. High in vivo oral
      efficacy was observed in both P.berghei and P. yoelii mouse models with IC50
      values comparable or better than those of chloroquine. The metabolic stability in
      different species and the pharmacokinetic profile in the mouse model makes AM1 a
      compound worth further investigation as a potential novel schizonticidal agent.

PMID- 29194349
TI  - Polymorphism Analysis of Ch1 and Ch2 Genes in the Siberian Cat.
AB  - Cats are usually spreaders of allergens that are critical for sensitive people;
      the Siberian cat is a breed supposed to be low level allergenic, according to
      some breeders' statements. The sequence of the two genes, namely Ch1 and Ch2,
      that code for the allergen Fel d 1, the major allergen responsible for outbreaks
      of allergy symptoms, is not yet known in the Siberian cat, and finding this was
      the aim of our investigation. Notably, our work is the first survey of the
      genetic structure of these genes in Siberian cats. The comparison of the
      sequences of Siberian cats, non-Siberian cats, and sequences present in the
      National Center for Biotechnology Information database revealed a considerable
      number of mutations; some of those detected in the Siberian cat, due to their
      position in exon regions, could affect the Fel d 1 allergenic properties.
      Therefore, further investigations are recommended to assess if the identified
      mutations can be responsible for a reduced-allergen synthesis and can be used as
      markers for selection of low level allergenic cats.

PMID- 29194348
TI  - alpha-Glucosidase and Protein Tyrosine Phosphatase 1B Inhibitory Activity of
      Plastoquinones from Marine Brown Alga Sargassum serratifolium.
AB  - Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales) is a marine brown alga
      that belongs to the family Sargassaceae. It is widely distributed throughout
      coastal areas of Korea and Japan. S. serratifolium has been found to contain high
      concentrations of plastoquinones, which have strong anti-cancer, anti
      inflammatory, antioxidant, and neuroprotective activity. This study aims to
      investigate the anti-diabetic activity of S. serratifolium and its major
      constituents through inhibition of protein tyrosine phosphatase 1B (PTP1B), alpha
      glucosidase, and ONOO--mediated albumin nitration. S. serratifolium ethanolic
      extract and fractions exhibited broad PTP1B and alpha-glucosidase inhibitory
      activity (IC50, 1.83~7.04 and 3.16~24.16 ug/mL for PTP1B and alpha-glucosidase,
      respectively). In an attempt to identify bioactive compounds, three
      plastoquinones (sargahydroquinoic acid, sargachromenol and sargaquinoic acid)
      were isolated from the active n-hexane fraction of S. serratifolium. All three
      plastoquinones exhibited dose-dependent inhibitory activity against PTP1B in the
      IC50 range of 5.14-14.15 uM, while sargachromenol and sargaquinoic acid showed
      dose-dependent inhibitory activity against alpha-glucosidase (IC50 42.41 +/- 3.09
      and 96.17 +/- 3.48 uM, respectively). In the kinetic study of PTP1B enzyme
      inhibition, sargahydroquinoic acid and sargaquinoic acid led to mixed-type
      inhibition, whereas sargachromenol displayed noncompetitive-type inhibition.
      Moreover, plastoquinones dose-dependently inhibited ONOO--mediated albumin
      nitration. Docking simulations of these plastoquinones demonstrated negative
      binding energies and close proximity to residues in the binding pocket of PTP1B
      and alpha-glucosidase, indicating that these plastoquinones have high affinity
      and tight binding capacity towards the active site of the enzymes. These results
      demonstrate that S. serratifolium and its major plastoquinones may have the
      potential as functional food ingredients for the prevention and treatment of type
      2 diabetes.

PMID- 29194350
TI  - The Marine Fungi Rhodotorula sp. (Strain CNYC4007) as a Potential Feed Source for
      Fish Larvae Nutrition.
AB  - Fish oil is used in the production of feed for cultured fish owing to its high
      polyunsaturated fatty acid content (PUFA). The over-exploitation of fisheries and
      events like "El Nino" are reducing the fish oil supply. Some marine
      microorganisms are considered potentially as alternative fatty acid sources. This
      study assesses a strain of Rhodotorula sp. (strain CNYC4007; 27% docosahexaenoic
      acid (DHA) of total fatty acids), as feed for fish larvae. The total length and
      ribonucleic acid (RNA)/deoxyribonucleic acid (DNA) ratio of Danio rerio larvae
      was determined at first feeding at six and 12 days old (post-yolk absorption
      larvae). Larvae fed with microencapsulated Rhodotorula sp. CNYC4007 had a
      significantly higher RNA/DNA ratio than control group (C1). At six days post-yolk
      absorption group, the RNA/DNA ratio of larvae fed with Rhodotorula sp.
      bioencapsulated in Brachionus sp. was significantly higher than control group fed
      with a commercial diet high in DHA (C2-DHA). Finally, at 12 days post-yolk
      absorption, the RNA/DNA ratio was significantly higher in larvae fed with
      Rhodotorula sp. CNYC4007 and C2-DHA (both bioencapsulated in Artemia sp. nauplii)
      than in control group (C1). These results suggest that Rhodotorula sp. CNYC4007
      can be an alternative source of DHA for feeding fish at larval stage, providing a
      sustainable source of fatty acids.

PMID- 29194351
TI  - Identification of a Raloxifene Analog That Promotes AhR-Mediated Apoptosis in
      Cancer Cells.
AB  - We previously reported that raloxifene, an estrogen receptor modulator, is also a
      ligand for the aryl hydrocarbon receptor (AhR). Raloxifene induces apoptosis in
      estrogen receptor-negative human cancer cells through the AhR. We performed
      structure-activity studies with seven raloxifene analogs to better understand the
      structural requirements of raloxifene for induction of AhR-mediated
      transcriptional activity and apoptosis. We identified Y134 as a raloxifene analog
      that activates AhR-mediated transcriptional activity and induces apoptosis in MDA
      MB-231 human triple negative breast cancer cells. Suppression of AhR expression
      strongly reduced apoptosis induced by Y134, indicating the requirement of AhR for
      Y134-induced apoptosis. Y134 also induced apoptosis in hepatoma cells without
      having an effect on cell cycle regulation. Toxicity testing on zebrafish embryos
      revealed that Y134 has a significantly better safety profile than raloxifene. Our
      studies also identified an analog of raloxifene that acts as a partial antagonist
      of the AhR, and is capable of inhibiting AhR agonist-induced transcriptional
      activity. We conclude that Y134 is a promising raloxifene analog for further
      optimization as an anti-cancer agent targeting the AhR.

PMID- 29194353
TI  - Reproductive Disorders and Leptospirosis: A Case Study in a Mixed-Species Farm
      (Cattle and Swine).
AB  - Animal leptospirosis, exempt in rodents, manifests as peculiar biology where the
      animal can function, simultaneously or not, as a susceptible host or reservoir.
      In the first case, clinical symptoms are likely. In the second case, infection is
      subclinical and manifestations are mild or absent. Mild clinical symptoms
      encompass reproductive failure in production animals for host-adapted Leptospira
      sp. serovars. This work presents a study on Leptospira sp. infection in a mixed
      species (bovine and swine) farm with documented reproductive disorders in the
      cattle unit. A long calving interval (above 450 days) was the hallmark observed
      in cows. Some cows (2/26 tested) presented a high titre of antibodies against
      Leptospira sp. serogroup Sejroe, but the overall within-herd prevalence was low
      (11.5% and 7.7% for cut-off titres of 1:30 and 1:100, respectively). The in-herd
      prevalence of leptospirosis in the sow unit (determined for 113/140 animals) was
      high when using a lowered cut-off threshold (32.7% vs. 1.8% for cut-off titre of
      1:30 and 1:100, respectively). In this unit, the most prevalent serogroup was
      Autumnalis. The final diagnostic confirmation of Leptospira sp. maintenance
      within the farm was obtained through detection by PCR of Leptospira sp. DNA in an
      aborted swine litter. Despite the fact that a common causative infective agent
      was diagnosed in both species, the direct link between the two animal units was
      not found. Factors such as drinking from the same water source and the use of
      manure prepared with the swine slurry might raise suspicion of a possible cross
      contamination between the two units. In conclusion, this work suggests that
      leptospirosis be included in the differential diagnosis of reproductive disorders
      and spontaneous abortions in production animals and provides data that justify
      the use of a lowered threshold cut-off for herd diagnosis.

PMID- 29194352
TI  - Structural Insights into the Cytotoxic Mechanism of Vibrio parahaemolyticus
      PirAvp and PirBvp Toxins.
AB  - In aquaculture, shrimp farming is a popular field. The benefits of shrimp farming
      include a relatively short grow-out time, high sale price, and good cost
      recovery. However, outbreaks of serious diseases inflict serious losses, and
      acute hepatopancreatic necrosis disease (AHPND) is an emerging challenge to this
      industry. In South American white shrimp (Penaeus vannamei) and grass shrimp
      (Penaeus monodon), this disease has a 70-100% mortality. The pathogenic agent of
      AHPND is a specific strain of Vibrio parahaemolyticus which contains PirAvp and
      PirBvp toxins encoded in the pVA1 plasmid. PirAvp and PirBvp have been shown to
      cause the typical histological symptoms of AHPND in infected shrimps, and in this
      review, we will focus on our structural understanding of these toxins. By
      analyzing their structures, a possible cytotoxic mechanism, as well as strategies
      for anti-AHPND drug design, is proposed.

PMID- 29194354
TI  - Assessment of GF-3 Polarimetric SAR Data for Physical Scattering Mechanism
      Analysis and Terrain Classification.
AB  - On 10 August 2016 China launched the GF-3, its first C-band polarimetric
      synthetic aperture radar (SAR) satellite, which was put into operation at the end
      of January, 2017. GF-3 polarimetric SAR has many advantages such as high
      resolution and multi-polarization imaging capabilities. Polarimetric SAR can
      fully characterize the backscatter property of targets, and thus it is of great
      interest to explore the physical scattering mechanisms of terrain types, which is
      very important in interpreting polarimetric SAR imagery and for its further
      usages in Earth observations. In this paper, focusing on target scattering
      characterization and feature extraction, we generalize the Delta alpha B / alpha
      B method, which was proposed under the reflection symmetric assumption, for the
      general backscatter process to account for both the reflection symmetry and
      asymmetry cases. Then, we evaluate the performances of physical scattering
      mechanism analysis methods for GF-3 polarimetric SAR imagery. Radarsat-2 data
      acquired over the same area is used for cross validation. Results show that GF-3
      polarimetric SAR data has great potential for target characterization, especially
      for ocean area observation.

PMID- 29194356
TI  - A Pseudorange Measurement Scheme Based on Snapshot for Base Station Positioning
      Receivers.
AB  - Digital multimedia broadcasting signal is promised to be a wireless positioning
      signal. This paper mainly studies a multimedia broadcasting technology, named
      China mobile multimedia broadcasting (CMMB), in the context of positioning.
      Theoretical and practical analysis on the CMMB signal suggests that the existing
      CMMB signal does not have the meter positioning capability. So, the CMMB system
      has been modified to achieve meter positioning capability by multiplexing the
      CMMB signal and pseudo codes in the same frequency band. The time difference of
      arrival (TDOA) estimation method is used in base station positioning receivers.
      Due to the influence of a complex fading channel and the limited bandwidth of
      receivers, the regular tracking method based on pseudo code ranging is difficult
      to provide continuous and accurate TDOA estimations. A pseudorange measurement
      scheme based on snapshot is proposed to solve the problem. This algorithm
      extracts the TDOA estimation from the stored signal fragments, and utilizes the
      Taylor expansion of the autocorrelation function to improve the TDOA estimation
      accuracy. Monte Carlo simulations and real data tests show that the proposed
      algorithm can significantly reduce the TDOA estimation error for base station
      positioning receivers, and then the modified CMMB system achieves meter
      positioning accuracy.

PMID- 29194355
TI  - Characterization of the EBV-Induced Persistent DNA Damage Response.
AB  - Epstein-Barr virus (EBV) is an oncogenic herpesvirus that is ubiquitous in the
      human population. Early after EBV infection in vitro, primary human B cells
      undergo a transient period of hyper-proliferation, which results in replicative
      stress and DNA damage, activation of the DNA damage response (DDR) pathway and,
      ultimately, senescence. In this study, we investigated DDR-mediated senescence in
      early arrested EBV-infected B cells and characterized the establishment of
      persistent DNA damage foci. We found that arrested EBV-infected B cells exhibited
      an increase in promyelocytic leukemia nuclear bodies (PML NBs), which
      predominantly localized to markers of DNA damage, as well as telomeric DNA.
      Furthermore, arrested EBV-infected B cells exhibited an increase in the presence
      of telomere dysfunction-induced foci. Importantly, we found that increasing human
      telomerase reverse transcriptase (hTERT) expression with danazol, a drug used to
      treat telomere diseases, permitted early EBV-infected B cells to overcome
      cellular senescence and enhanced transformation. Finally, we report that EBV
      infected B cells undergoing hyper-proliferation are more sensitive than
      lymphoblastoid cell lines (LCLs) to inhibition of Bloom syndrome-associated
      helicase, which facilitates telomere replication. Together, our results describe
      the composition of persistent DNA damage foci in the early stages of EBV
      infection and define key regulators of this barrier to long-term outgrowth.

PMID- 29194357
TI  - A Direct Bicarbonate Detection Method Based on a Near-Concentric Cavity-Enhanced
      Raman Spectroscopy System.
AB  - Raman spectroscopy has great potential as a tool in a variety of hydrothermal
      science applications. However, its low sensitivity has limited its use in common
      sea areas. In this paper, we develop a near-concentric cavity-enhanced Raman
      spectroscopy system to directly detect bicarbonate in seawater for the first
      time. With the aid of this near-concentric cavity-enhanced Raman spectroscopy
      system, a significant enhancement in HCO3- detection has been achieved. The
      obtained limit of detection (LOD) is determined to be 0.37 mmol/L-much lower than
      the typical concentration of HCO3- in seawater. By introducing a specially
      developed data processing scheme, the weak HCO3- signal is extracted from the
      strong sulfate signal background, hence a quantitative analysis with R2 of 0.951
      is made possible. Based on the spectra taken from deep sea seawater sampling, the
      concentration of HCO3- has been determined to be 1.91 mmol/L, with a relative
      error of 2.1% from the reported value (1.95 mmol/L) of seawater in the ocean. It
      is expected that the near-concentric cavity-enhanced Raman spectroscopy system
      could be developed and used for in-situ ocean observation in the near future.

PMID- 29194358
TI  - Automated Ecological Assessment of Physical Activity: Advancing Direct
      Observation.
AB  - Technological advances provide opportunities for automating direct observations
      of physical activity, which allow for continuous monitoring and feedback. This
      pilot study evaluated the initial validity of computer vision algorithms for
      ecological assessment of physical activity. The sample comprised 6630 seconds per
      camera (three cameras in total) of video capturing up to nine participants
      engaged in sitting, standing, walking, and jogging in an open outdoor space while
      wearing accelerometers. Computer vision algorithms were developed to assess the
      number and proportion of people in sedentary, light, moderate, and vigorous
      activity, and group-based metabolic equivalents of tasks (MET)-minutes. Means and
      standard deviations (SD) of bias/difference values, and intraclass correlation
      coefficients (ICC) assessed the criterion validity compared to accelerometry
      separately for each camera. The number and proportion of participants sedentary
      and in moderate-to-vigorous physical activity (MVPA) had small biases (within 20%
      of the criterion mean) and the ICCs were excellent (0.82-0.98). Total MET-minutes
      were slightly underestimated by 9.3-17.1% and the ICCs were good (0.68-0.79). The
      standard deviations of the bias estimates were moderate-to-large relative to the
      means. The computer vision algorithms appeared to have acceptable sample-level
      validity (i.e., across a sample of time intervals) and are promising for
      automated ecological assessment of activity in open outdoor settings, but further
      development and testing is needed before such tools can be used in a diverse
      range of settings.

PMID- 29194359
TI  - Chikungunya Virus: Pathophysiology, Mechanism, and Modeling.
AB  - Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, is recurring in
      epidemic waves. In the past decade and a half, the disease has resurged in
      several countries around the globe, with outbreaks becoming increasingly severe.
      Though CHIKV was first isolated in 1952, there remain significant gaps in
      knowledge of CHIKV biology, pathogenesis, transmission, and mechanism. Diagnosis
      is largely simplified and based on symptoms, while treatment is supportive rather
      than curative. Here we present an overview of the disease, the challenges that
      lie ahead for future research, and what directions current studies are headed
      towards, with emphasis on improvement of current animal models and potential use
      of 3D models.

PMID- 29194360
TI  - The Modulation of NMDA and AMPA/Kainate Receptors by Tocotrienol-Rich Fraction
      and Alpha-Tocopherol in Glutamate-Induced Injury of Primary Astrocytes.
AB  - Astrocytes are known as structural and supporting cells in the central nervous
      system (CNS). Glutamate, as a main excitatory amino acid neurotransmitter in the
      mammalian central nervous system, can be excitotoxic, playing a key role in many
      chronic neurodegenerative diseases. The aim of the current study was to elucidate
      the potential of vitamin E in protecting glutamate-injured primary astrocytes.
      Hence, primary astrocytes were isolated from mixed glial cells of C57BL/6 mice by
      applying the EasySep(r) Mouse CD11b Positive Selection Kit, cultured in
      Dulbecco's modified Eagle medium (DMEM) and supplemented with special nutrients.
      The IC20 and IC50 values of glutamate, as well as the cell viability of primary
      astrocytes, were assessed with 100 ng/mL, 200 ng/mL, and 300 ng/mL of tocotrienol
      rich fraction (TRF) and alpha-tocopherol (alpha-TCP), as determined by an 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The
      mitochondrial membrane potential (MMP) detected in primary astrocytes was
      assessed with the same concentrations of TRF and alpha-TCP. The expression levels
      of the ionotropic glutamate receptor genes (Gria2, Grin2A, GRIK1) were
      independently determined using RT-PCR. The purification rate of astrocytes was
      measured by a flow-cytometer as circa 79.4%. The IC20 and IC50 values of
      glutamate were determined as 10 mM and 100 mM, respectively. Exposure to 100 mM
      of glutamate in primary astrocytes caused the inhibition of cell viability of
      approximately 64.75% and 61.10% in pre- and post-study, respectively (p < 0.05).
      Both TRF and alpha-TCP (at the lowest and highest concentrations, respectively)
      were able to increase the MMP to 88.46% and 93.31% pre-treatment, and 78.43% and
      81.22% post-treatment, respectively. Additionally, the findings showed a similar
      pattern for the expression level of the ionotropic glutamate receptor genes.
      Increased extracellular calcium concentrations were also observed, indicating
      that the presence of vitamin E altered the polarization of astrocytes. In
      conclusion, alpha-TCP showed better recovery and prophylactic effects as compared
      to TRF in the pre-treatment of glutamate-injured primary astrocytes.

PMID- 29194361
TI  - Social Networks, Engagement and Resilience in University Students.
AB  - Analysis of social networks may be a useful tool for understanding the
      relationship between resilience and engagement, and this could be applied to
      educational methodologies, not only to improve academic performance, but also to
      create emotionally sustainable networks. This descriptive study was carried out
      on 134 university students. We collected the network structural variables, degree
      of resilience (CD-RISC 10), and engagement (UWES-S). The computer programs used
      were excel, UCINET for network analysis, and SPSS for statistical analysis. The
      analysis revealed results of means of 28.61 for resilience, 2.98 for absorption,
      4.82 for dedication, and 3.13 for vigour. The students had two preferred places
      for sharing information: the classroom and WhatsApp. The greater the value for
      engagement, the greater the degree of centrality in the friendship network among
      students who are beginning their university studies. This relationship becomes
      reversed as the students move to later academic years. In terms of resilience,
      the highest values correspond to greater centrality in the friendship networks.
      The variables of engagement and resilience influenced the university students'
      support networks.

PMID- 29194362
TI  - The Small Regulatory RNA Spot42 Inhibits Indole Biosynthesis to Negatively
      Regulate the Locus of Enterocyte Effacement of Enteropathogenic Escherichia coli.
AB  - The locus of enterocyte effacement is necessary for enteropathogenic Escherichia
      coli (EPEC) to form attaching and effacing (A/E) lesions. A/E lesions are
      characterized by intimate bacterial adherence to intestinal cells and destruction
      of microvilli, which leads to diarrhea. Therefore, studies interrogating the
      regulation of the locus of enterocyte effacement (LEE) are critical for
      understanding the molecular epidemiology of EPEC infections and developing
      interventional strategies. Hitherto, most studies have centered on protein-based
      regulators, whereas the role of small regulatory RNAs remains underappreciated.
      Previously, we identified the first sRNAs-MgrR, RyhB, and McaS-that regulate the
      LEE of EPEC. This study was undertaken to identify additional sRNAs that impact
      the LEE. Our results suggest that the catabolite-responsive sRNA, Spot42,
      indirectly controls the LEE by inhibiting synthesis of its inducer, indole.
      Spot42 base-pairs with the tnaCAB mRNA and presumably destabilizes the
      transcript, thereby preventing expression of the regulatory and structural
      proteins that are involved in the import and hydrolysis of tryptophan into
      indole. The absence of intracellular indole leads to reduced transcription of the
      LEE1-encoded master transcriptional activator Ler, thereby maintaining the LEE in
      its silenced state and delaying A/E lesion morphogenesis. Our results highlight
      the importance of riboregulators that synchronize metabolic and virulence
      pathways in bacterial infection.

PMID- 29194363
TI  - The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling.
AB  - The three CARD-containing MAGUK (CARMA) proteins function as scaffolding
      molecules that regulate activation of the pro-inflammatory transcription factor
      NF-kappaB. Recently, mutations in CARMA2 have been linked to psoriasis
      susceptibility due to their acquired altered capacity to activate NF-kappaB. By
      means of two-hybrid screening with yeast, we identified RING finger protein 7
      (RNF7) as an interactor of CARMA2. We present evidence that RNF7 functions as a
      negative regulator of the NF-kappaB-activating capacity of CARMA2.
      Mechanistically, RNF7 influences CARMA2 signaling by regulating the
      ubiquitination state of MALT1 and the NF-kappaB-regulatory molecule NEMO.
      Interestingly, CARMA2short (CARMA2sh) mutants associated with psoriasis
      susceptibility escape the negative control exerted by RNF7. In conclusion, our
      findings identify a new mechanism through which the ability of CARMA2 to activate
      NF-kappaB is regulated, which could have significant implications for our
      understanding of why mutations of this protein trigger human psoriasis.

PMID- 29194364
TI  - Resveratrol Role in Autoimmune Disease-A Mini-Review.
AB  - Autoimmune diseases are still considered to be pressing concerns due the fact
      that they are leaders in death and disability causes worldwide. Resveratrol is a
      polyphenol derived from a variety of foods and beverages, including red grapes
      and red wine. Anti-inflammatory, antioxidant, and antiaging properties of
      resveratrol have been reported, and in some animal and human studies this
      compound reduced and ameliorated the progression of autoimmune diseases, such as
      rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel
      disease, and type 1 diabetes mellitus. Thus, this review aims to summarize and
      critically analyze the role of resveratrol in the modulation of several organ
      specific or systemic autoimmune diseases.

PMID- 29194366
TI  - Exploring the Impact of Food on the Gut Ecosystem Based on the Combination of
      Machine Learning and Network Visualization.
AB  - Prebiotics and probiotics strongly impact the gut ecosystem by changing the
      composition and/or metabolism of the microbiota to improve the health of the
      host. However, the composition of the microbiota constantly changes due to the
      intake of daily diet. This shift in the microbiota composition has a considerable
      impact; however, non-pre/probiotic foods that have a low impact are ignored
      because of the lack of a highly sensitive evaluation method. We performed
      comprehensive acquisition of data using existing measurements (nuclear magnetic
      resonance, next-generation DNA sequencing, and inductively coupled plasma-optical
      emission spectroscopy) and analyses based on a combination of machine learning
      and network visualization, which extracted important factors by the Random Forest
      approach, and applied these factors to a network module. We used two
      pteridophytes, Pteridium aquilinum and Matteuccia struthiopteris, for the
      representative daily diet. This novel analytical method could detect the impact
      of a small but significant shift associated with Matteuccia struthiopteris but
      not Pteridium aquilinum intake, using the functional network module. In this
      study, we proposed a novel method that is useful to explore a new valuable food
      to improve the health of the host as pre/probiotics.

PMID- 29194367
TI  - Safety Aspects of Bio-Based Nanomaterials.
AB  - Moving towards a bio-based and circular economy implies a major focus on the
      responsible and sustainable utilization of bio-resources. The emergence of
      nanotechnology has opened multiple possibilities, not only in the existing
      industrial sectors, but also for completely novel applications of nanoscale bio
      materials, the commercial exploitation of which has only begun during the last
      few years. Bio-based materials are often assumed not to be toxic. However, this
      pre-assumption is not necessarily true. Here, we provide a short overview on
      health and environmental aspects associated with bio-based nanomaterials, and on
      the relevant regulatory requirements. We also discuss testing strategies that may
      be used for screening purposes at pre-commercial stages. Although the tests
      presently used to reveal hazards are still evolving, regarding modifi-cations
      required for nanomaterials, their application is needed before the upscaling or
      commercialization of bio-based nanomaterials, to ensure the market potential of
      the nanomaterials is not delayed by uncertainties about safety issues.

PMID- 29194368
TI  - Vitamin D: Moving Forward to Address Emerging Science.
AB  - The science surrounding vitamin D presents both challenges and opportunities.
      Although many uncertainties are associated with the understandings concerning
      vitamin D, including its physiological function, the effects of excessive intake,
      and its role in health, it is at the same time a major interest in the research
      and health communities. The approach to evaluating and interpreting the available
      evidence about vitamin D should be founded on the quality of the data and on the
      conclusions that take into account the totality of the evidence. In addition,
      these activities can be used to identify critical data gaps and to help structure
      future research. The Office of Dietary Supplements (ODS) at the National
      Institutes of Health has as part of its mission the goal of supporting research
      and dialogues for topics with uncertain data, including vitamin D. This review
      considers vitamin D in the context of systematically addressing the uncertainty
      and in identifying research needs through the filter of the work of ODS. The
      focus includes the role of systematic reviews, activities that encompass
      considerations of the totality of the evidence, and collaborative activities to
      clarify unknowns or to fix methodological problems, as well as a case study using
      the relationship between cancer and vitamin D.

PMID- 29194365
TI  - The Role of Resveratrol in Cancer Therapy.
AB  - Abstract: Natural product compounds have recently attracted significant attention
      from the scientific community for their potent effects against inflammation
      driven diseases, including cancer. A significant amount of research, including
      preclinical, clinical, and epidemiological studies, has indicated that dietary
      consumption of polyphenols, found at high levels in cereals, pulses, vegetables,
      and fruits, may prevent the evolution of an array of diseases, including cancer.
      Cancer development is a carefully orchestrated progression where normal cells
      acquires mutations in their genetic makeup, which cause the cells to continuously
      grow, colonize, and metastasize to other organs such as the liver, lungs, colon,
      and brain. Compounds that modulate these oncogenic processes can be considered as
      potential anti-cancer agents that may ultimately make it to clinical application.
      Resveratrol, a natural stilbene and a non-flavonoid polyphenol, is a
      phytoestrogen that possesses anti-oxidant, anti-inflammatory, cardioprotective,
      and anti-cancer properties. It has been reported that resveratrol can reverse
      multidrug resistance in cancer cells, and, when used in combination with
      clinically used drugs, it can sensitize cancer cells to standard chemotherapeutic
      agents. Several novel analogs of resveratrol have been developed with improved
      anti-cancer activity, bioavailability, and pharmacokinetic profile. The current
      focus of this review is resveratrol's in vivo and in vitro effects in a variety
      of cancers, and intracellular molecular targets modulated by this polyphenol.
      This is also accompanied by a comprehensive update of the various clinical trials
      that have demonstrated it to be a promising therapeutic and chemopreventive
      agent.

PMID- 29194369
TI  - Elevated Systemic IL-6 Levels in Patients with Aneurysmal Subarachnoid Hemorrhage
      Is an Unspecific Marker for Post-SAH Complications.
AB  - Background: Aneurysmal subarachnoid hemorrhage (aSAH) is still a fatal and morbid
      disease, although bleeding aneurysms can be secured in almost all cases.
      Occurrence of post-SAH complications including cerebral vasospasm, delayed
      cerebral ischemia, hydrocephalus, epilepsy, and infections are the main
      determinants of clinical outcome. Hence, it is important to search for early
      predictors for specific post-SAH complications to treat these complications
      properly. Both cellular and molecular (cytokines) inflammation play a key role
      after aSAH during the phase of occurrence of post-SAH complications. Interleukin
      6 (IL-6) is a well-known cytokine that has been extensively analyzed in
      cerebrospinal fluid (CSF) of patients after aSAH, but detailed studies exploring
      the role of systemic IL-6 in aSAH associated complications and its impact on
      early clinical outcome prediction are lacking. The current study aims to analyze
      the systemic IL-6 levels over two weeks after bleeding and its role in post-SAH
      complications. Methods: We recruited 80 aSAH patients prospectively who underwent
      peripheral venous blood withdrawal in serum gel tubes. The blood was centrifuged
      to harvest the serum, which was immediately frozen at -80  degrees C until
      analysis. Serum IL-6 levels were quantified using Immulite immunoassay system.
      Patient records including age, gender, post-SAH complications, aneurysm
      treatment, and clinical outcome (modified Rankin scale and Glasgow outcome scale)
      were retrieved to allow different subgroup analysis. Results: Serum IL-6 levels
      were significantly raised after aSAH compared to healthy controls over the first
      two weeks after hemorrhage. Serum IL-6 levels were found to be significantly
      elevated in aSAH patients presenting with higher Hunt and Hess grades, increasing
      age, and both intraventricular and intracerebral hemorrhage. Interestingly, serum
      IL-6 was also significantly raised in aSAH patients who developed seizures,
      cerebral vasospasm (CVS), and chronic hydrocephalus. IL-6 levels were sensitive
      to the development of infections and showed an increase in patients who developed
      pneumoniae. Intriguingly, we found a delayed increase in serum IL-6 in patients
      developing cerebral infarction. Finally, IL-6 levels were significantly higher in
      patients presenting with poor clinical outcome in comparison to good clinical
      outcome at discharge from hospital. Conclusion: Serum IL-6 levels were elevated
      early after aSAH and remained high over the two weeks after initial bleeding.
      Serum IL-6 was elevated in different aSAH associated complications, acting as a
      non-specific marker for post-SAH complications and an important biomarker for
      clinical outcome at discharge.

PMID- 29194371
TI  - In Vivo Imaging of Prostate Cancer Tumors and Metastasis Using Non-Specific
      Fluorescent Nanoparticles in Mice.
AB  - With the growing interest in the use of nanoparticles (NPs) in nanomedicine,
      there is a crucial need for imaging and targeted therapies to determine NP
      distribution in the body after systemic administration, and to achieve strong
      accumulation in tumors with low background in other tissues. Accumulation of NPs
      in tumors results from different mechanisms, and appears extremely heterogeneous
      in mice models and rather limited in humans. Developing new tumor models in mice,
      with their low spontaneous NP accumulation, is thus necessary for screening
      imaging probes and for testing new targeting strategies. In the present work,
      accumulation of LipImageTM 815, a non-specific nanosized fluorescent imaging
      agent, was compared in subcutaneous, orthotopic and metastatic tumors of RM1
      cells (murine prostate cancer cell line) by in vivo and ex vivo fluorescence
      imaging techniques. LipImageTM 815 mainly accumulated in liver at 24 h but also
      in orthotopic tumors. Limited accumulation occurred in subcutaneous tumors, and
      very low fluorescence was detected in metastasis. Altogether, these different
      tumor models in mice offered a wide range of NP accumulation levels, and a panel
      of in vivo models that may be useful to further challenge NP targeting
      properties.

PMID- 29194370
TI  - Alternative Oral Agents in Prophylaxis and Therapy of Uterine Fibroids-An Up-to
      Date Review.
AB  - Uterine fibroids (UFs) are the most common tumors of the female genital tract.
      The effect of UFs on the quality of life and the overall cost of treatment are
      significant issues worldwide. Tumor size and location are the two specific
      factors which influence the occurrence of symptoms, the need for, and method of,
      treatment (some tumors require surgery while some can be treated with selected
      drugs). Primary prevention and treatment of early UF disease are worthy goals
      that might have a great impact on health care systems. Several treatments and
      prophylactic methods can be used in this endeavor. This publication presents
      current data about lesser-known substances which may have a beneficial effect on
      the treatment or prophylaxis of UFs and can be administered orally, serving as an
      alternative to (or complement of) surgery or selective progesterone receptor
      modulators (SPRMs). Early prevention and treatment of UFs in women from high-risk
      groups should be our priority. Innovative forms of UF management are under
      intensive investigation and may be promising options in the near future. Many of
      them evaluated vitamin D, paricalcitol, epigallocatechin gallate (EGCG),
      elagolix, aromatase inhibitors (AIs), and cabergoline and deemed them to be safe
      and effective. The next step in such projects should be properly constructed
      randomized control trials (RCTs), carried out by successive phases.

PMID- 29194373
TI  - Anti-Proliferative Activity of Triterpenoids and Sterols Isolated from Alstonia
      scholaris against Non-Small-Cell Lung Carcinoma Cells.
AB  - (1) Background: In China and South Asia, Alstonia scholaris (Apocynaceae) is an
      important medicinal plant that has been historically used in traditional
      ethnopharmacy to treat infectious diseases. Although various pharmacological
      activities have been reported, the anti-lung cancer components of A. scholaris
      have not yet been identified. The objective of this study is to evaluate the
      active components of the leaf extract of A. scholaris, and assess the anti
      proliferation effects of isolated compounds against non-small-cell lung carcinoma
      cells; (2) Methods: NMR was used to identify the chemical constitutes isolated
      from the leaf extract of A. scholaris. The anti-proliferative activity of
      compounds against non-small-cell lung carcinoma cells was assessed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (3) Results:
      Eight triterpenoids and five sterols were isolated from the hexane portion of A.
      scholaris, and structurally identified as: (1) ursolic acid, (2) oleanolic acid,
      (3) betulinic acid, (4) betulin, (5) 2beta,3beta,28-lup-20(29)-ene-triol, (6)
      lupeol, (7) beta-amyrin, (8) alpha-amyrin, (9) poriferasterol, (10)
      epicampesterol, (11) beta-sitosterol, (12) 6beta-hydroxy-4-stigmasten-3-one, and
      (13) ergosta-7,22-diene-3beta,5alpha,6beta-triol. Compound 5 was isolated from a
      plant source for the first time. In addition, compounds 9, 10, 12, and 13 were
      also isolated from A. scholaris for the first time. Ursolic acid, betulinic acid,
      betulin, and 2beta,3beta,28-lup-20(29)-ene-triol showed anti-proliferative
      activity against NSCLC, with IC50 of 39.8, 40.1, 240.5 and 172.6 MUM,
      respectively.; (4) Conclusion: These findings reflect that pentacyclic
      triterpenoids are the anti-lung cancer chemicals in A. scholaris. The ability of
      ursolic acid, betulinic acid, betulin, and 2beta,3beta,28-lup-20(29)-ene-triol to
      inhibit the proliferative activity of NSCLC can constitute a valuable group of
      therapeutic agents in the future.

PMID- 29194372
TI  - What Is Our Current Understanding of PrPSc-Associated Neurotoxicity and Its
      Molecular Underpinnings?
AB  - The prion diseases are a collection of fatal, transmissible neurodegenerative
      diseases that cause rapid onset dementia and ultimately death. Uniquely, the
      infectious agent is a misfolded form of the endogenous cellular prion protein,
      termed PrPSc. Despite the identity of the molecular agent remaining the same,
      PrPSc can cause a range of diseases with hereditary, spontaneous or iatrogenic
      aetiologies. However, the link between PrPSc and toxicity is complex, with
      subclinical cases of prion disease discovered, and prion neurodegeneration
      without obvious PrPSc deposition. The toxic mechanisms by which PrPSc causes the
      extensive neuropathology are still poorly understood, although recent advances
      are beginning to unravel the molecular underpinnings, including oxidative stress,
      disruption of proteostasis and induction of the unfolded protein response. This
      review will discuss the diseases caused by PrPSc toxicity, the nature of the
      toxicity of PrPSc, and our current understanding of the downstream toxic
      signaling events triggered by the presence of PrPSc.

PMID- 29194374
TI  - Subcellular Interactions during Vascular Morphogenesis in 3D Cocultures between
      Endothelial Cells and Fibroblasts.
AB  - BACKGROUND: Increasing the complexity of in vitro systems to mimic three
      dimensional tissues and the cellular interactions within them will increase the
      reliability of data that were previously collected with in vitro systems. In vivo
      vascularization is based on complex and clearly defined cell-matrix and cell-cell
      interactions, where the extracellular matrix (ECM) seems to play a very important
      role. The aim of this study was to monitor and visualize the subcellular and
      molecular interactions between endothelial cells (ECs), fibroblasts, and their
      surrounding microenvironment during vascular morphogenesis in a three-dimensional
      coculture model. METHODS: Quantitative and qualitative analyses during the
      generation of a coculture tissue construct consisting of endothelial cells and
      fibroblasts were done using transmission electron microscopy and
      immunohistochemistry. RESULTS: Dynamic interactions were found in cocultures
      between ECs, between fibroblasts (FBs), between ECs and FBs, and between the
      cells and the ECM. Microvesicles were involved in intercellular information
      transfer. FBs took an active and physical part in the angiogenesis process. The
      ECM deposited by the cells triggered endothelial angiogenic activity. Capillary
      like tubular structures developed and matured. Moreover, some ECM assembled into
      a basement membrane (BM) having three different layers equivalent to those seen
      in vivo. Finally, the three-dimensional in vitro construct mirrored the
      topography of histological tissue sections. CONCLUSION: Our results visualize the
      importance of the physical contact between all cellular and acellular components
      of the cocultures.

PMID- 29194376
TI  - Research and Development of a DNDC Online Model for Farmland Carbon Sequestration
      and GHG Emissions Mitigation in China.
AB  - Appropriate agricultural practices for carbon sequestration and emission
      mitigation have a significant influence on global climate change. However,
      various agricultural practices on farmland carbon sequestration usually have a
      major impact on greenhouse gas (GHG) emissions. It is very important to
      accurately quantify the effect of agricultural practices. This study developed a
      platform-the Denitrification Decomposition (DNDC) online model-for simulating and
      evaluating the agricultural carbon sequestration and emission mitigation based on
      the scientific process of the DNDC model, which is widely used in the simulation
      of soil carbon and nitrogen dynamics. After testing the adaptability of the
      platform on two sampling fields, it turned out that the simulated values matched
      the measured values well for crop yields and GHG emissions. We used the platform
      to estimate the effect of three carbon sequestration practices in a sampling
      field: nitrogen fertilization reduction, straw residue and midseason drainage.
      The results indicated the following: (1) moderate decrement of the nitrogen
      fertilization in the sampling field was able to decrease the N2O emission while
      maintaining the paddy rice yield; (2) ground straw residue had almost no
      influence on paddy rice yield, but the CH4 emission and the surface SOC
      concentration increased along with the quantity of the straw residue; (3)
      compared to continuous flooding, midseason drainage would not decrease the paddy
      rice yield and could lead to a drop in CH4 emission. Thus, this study established
      the DNDC online model, which is able to serve as a reference and support for the
      study and evaluation of the effects of agricultural practices on agricultural
      carbon sequestration and GHG emissions mitigation in China.

PMID- 29194375
TI  - Cognitive and Behavioral Consequences of Sleep Disordered Breathing in Children.
AB  - There is now a plethora of evidence that children with sleep disordered breathing
      (SDB) show deficits in neurocognitive performance, behavioral impairments, and
      school performance. The following review will focus on the neurobehavioral
      impacts of SDB, pediatric sleep investigation challenges, potential mechanisms of
      behavioral and cognitive deficits in children with SDB, and the impact of SDB
      treatment.

PMID- 29194377
TI  - Optimization of Bioactive Polyphenols Extraction from Picea Mariana Bark.
AB  - Reported for its antioxidant, anti-inflammatory and non-toxicity properties, the
      hot water extract of Picea mariana bark was demonstrated to contain highly
      valuable bioactive polyphenols. In order to improve the recovery of these
      molecules, an optimization of the extraction was performed using water. Several
      extraction parameters were tested and extracts obtained analyzed both in terms of
      relative amounts of different phytochemical families and of individual molecules
      concentrations. As a result, low temperature (80  degrees C) and low ratio of
      bark/water (50 mg/mL) were determined to be the best parameters for an efficient
      polyphenol extraction and that especially for low molecular mass polyphenols.
      These were identified as stilbene monomers and derivatives, mainly stilbene
      glucoside isorhapontin (up to 12.0% of the dry extract), astringin (up to 4.6%),
      resveratrol (up to 0.3%), isorhapontigenin (up to 3.7%) and resveratrol glucoside
      piceid (up to 3.1%) which is here reported for the first time for Picea mariana.
      New stilbene derivatives, piceasides O and P were also characterized herein as
      new isorhapontin dimers. This study provides novel information about the optimal
      extraction of polyphenols from black spruce bark, especially for highly bioactive
      stilbenes including the trans-resveratrol.

PMID- 29194378
TI  - Chitosan Nanoparticles as a Mucoadhesive Drug Delivery System for Ocular
      Administration.
AB  - Pharmaceutical approaches based on nanotechnologies and the development of eye
      drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are
      emerging strategies for the efficient treatment of ocular diseases. These
      innovative nanoparticulate systems aim to increase drugs' bioavailability at the
      ocular surface. For the successful development of these systems, the evaluation
      of mucoahesiveness (the interaction between the ocular delivery system and mucins
      present on the eye) is of utmost importance. In this context, the aim of the
      present work was to investigate the mucoadhesivity of a novel nanoparticle eye
      drop formulation containing an antibiotic (ceftazidime) intended to treat eye
      infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl
      cellulose (HPMC) 0.75% (w/v) in an isotonic solution incorporating
      chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles
      containing ceftazidime. The viscosity of the nanoparticles, and the gels
      incorporating the nanoparticles were characterized in contact with mucin at
      different mass ratios, allowing the calculation of the rheological synergism
      parameter (?eta). Results showed that at different nanoparticle eye
      formulation:mucin weight ratios, a minimum in viscosity occurred which resulted
      in a negative rheological synergism. Additionally, the results highlighted the
      mucoadhesivity of the novel ocular formulation and its ability to interact with
      the ocular surface, thus increasing the drug residence time in the eye. Moreover,
      the in vitro release and permeation studies showed a prolonged drug release
      profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation.
      Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell
      lines, evaluated by the metabolic and membrane integrity tests. The formulation
      was stable and the drug active, as shown by microbiological studies. In
      conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a
      promising platform for ocular drug delivery with enhanced mucoadhesive
      properties.

PMID- 29194379
TI  - Isolation and Characterization of Serum Extracellular Vesicles (EVs) from
      Atlantic Salmon Infected with Piscirickettsia Salmonis.
AB  - Secretion of extracellular vesicles (EVs) is a common feature of both eukaryotic
      and prokaryotic cells. Isolated EVs have been shown to contain different types of
      molecules, including proteins and nucleic acids, and are reported to be key
      players in intercellular communication. Little is known, however, of EV secretion
      in fish, or the effect of infection on EV release and content. In the present
      study, EVs were isolated from the serum of healthy and Piscirickettsia salmonis
      infected Atlantic salmon in order to evaluate the effect of infection on EV
      secretion. P. salmonis is facultative intracellular bacterium that causes a
      systemic infection disease in farmed salmonids. EVs isolated from both infected
      and non-infected fish had an average diameter of 230-300 nm, as confirmed by
      transmission electron microscopy, nanoparticle tracking, and flow cytometry. Mass
      spectrometry identified 180 proteins in serum EVs from both groups of fish.
      Interestingly, 35 unique proteins were identified in serum EVs isolated from the
      fish infected with P. salmonis. These unique proteins included proteasomes
      subunits, granulins, and major histocompatibility class I and II. Our results
      suggest that EV release could be part of a mechanism in which host stimulatory
      molecules are released from infected cells to promote an immune response.

PMID- 29194380
TI  - Effect of Marine-Derived Ice-Binding Proteins on the Cryopreservation of Marine
      Microalgae.
AB  - Ice-binding protein (IBPs) protect cells from cryo-injury during cryopreservation
      by inhibiting ice recrystallization (IR), which is a main cause of cell death. In
      the present study, we employed two IBPs, one, designated LeIBP from Arctic yeast,
      and the other, designated FfIBP from Antarctic sea ice bacterium, in the
      cryopreservation of three economically valuable marine microalgae, Isochrysis
      galbana, Pavlova viridis, and Chlamydomonas coccoides. Both of the IBPs showed IR
      inhibition in f/2 medium containing 10% DMSO, indicating that they retain their
      function in freezing media. Microalgal cells were frozen in 10% DMSO with or
      without IBP. Post-thaw viability exhibited that the supplementation of IBPs
      increased the viability of all cryopreserved cells. LeIBP was effective in P.
      viridis and C. coccoides, while FfIBP was in I. galbana. The cryopreservative
      effect was more drastic with P. viridis when 0.05 mg/mL LeIBP was used. These
      results clearly demonstrate that IBPs could improve the viability of
      cryopreserved microalgal cells.

PMID- 29194381
TI  - Chemical Diversity from a Chinese Marine Red Alga, Symphyocladia latiuscula.
AB  - This study describes an investigation into secondary metabolites that are
      produced by a marine red alga, Symphyocladia latiuscula, which was collected from
      coastal waters off Qingdao, China. A combination of normal, reversed phase, and
      gel chromatography was used to isolate six citric acid derived natural products,
      aconitates A-F (1-6), together with two known and ten new polybrominated phenols,
      symphyocladins C/D (7a/b), and symphyocladins H-Q (8a/b, 9a/b and 10-15),
      respectively. Structure elucidation was achieved by detailed spectroscopic
      (including X-ray crystallographic) analysis. We propose a plausible and
      convergent biosynthetic pathway involving a key quinone methide intermediate,
      linking aconitates and symphyocladins.

PMID- 29194383
TI  - A Facile Approach to Tune the Electrical and Thermal Properties of Graphene
      Aerogels by Including Bulk MoS2.
AB  - Graphene aerogels (GAs) have attracted extensive interest in diverse fields,
      owing to their ultrahigh surface area, low density and decent electrical
      conductivity. However, the undesirable thermal conductivity of GAs may limit
      their applications in energy storage devices. Here, we report a facile
      hydrothermal method to modulate both the electrical and thermal properties of GAs
      by including bulk molybdenum disulfide (MoS2). It was found that MoS2 can help to
      reduce the size of graphene sheets and improve their dispersion, leading to the
      uniform porous micro-structure of GAs. The electrical measurement showed that the
      electrical conductivity of GAs could be decreased by 87% by adding 0.132 vol % of
      MoS2. On the contrary, the thermal conductivity of GAs could be increased by ~51%
      by including 0.2 vol % of MoS2. The quantitative investigation demonstrated that
      the effective medium theories (EMTs) could be applied to predict the thermal
      conductivity of composite GAs. Our findings indicated that the electrical and
      thermal properties of GAs can be tuned for the applications in various fields.

PMID- 29194382
TI  - Liposomal and Deoxycholate Amphotericin B Formulations: Effectiveness against
      Biofilm Infections of Candida spp.
AB  - BACKGROUND: candidiasis is the primary fungal infection encountered in patients
      undergoing prolonged hospitalization, and the fourth leading cause of nosocomial
      bloodstream infections. One of the most important Candida spp. virulence factors
      is the ability to form biofilms, which are extremely refractory to antimicrobial
      therapy and very difficult to treat with the traditional antifungal therapies. It
      is known that the prophylaxis or treatment of a systemic candidiasis are
      recurrently taken without considering the possibility of a Candida spp. biofilm
      related infections. Therefore, it is important to assess the effectiveness of the
      available drugs and which formulations have the best performance in these
      specific infections. METHODS: 24-h-biofilms of four Candida spp. and their
      response to two amphotericin B (AmB) pharmaceutical formulations (liposomal and
      deoxycholate) were evaluated. RESULTS: generally, Candida glabrata was the less
      susceptible yeast species to both AmBs. MBECs revealed that it is therapeutically
      more appealing to use AmB-L than AmB-Deox for all Candida spp. biofilms, since
      none of the determined concentrations of AmB-L reached 10% of the maximum daily
      dose, but both formulations showed a very good capacity in the biomass reduction.
      CONCLUSIONS: the liposomal formulation presents better performance in the
      eradication of the biofilm cells for all the species in comparison with the
      deoxycholate formulation.

PMID- 29194384
TI  - PCA Based Stress Monitoring of Cylindrical Specimens Using PZTs and Guided Waves.
AB  - Since mechanical stress in structures affects issues such as strength, expected
      operational life and dimensional stability, a continuous stress monitoring scheme
      is necessary for a complete integrity assessment. Consequently, this paper
      proposes a stress monitoring scheme for cylindrical specimens, which are widely
      used in structures such as pipelines, wind turbines or bridges. The approach
      consists of tracking guided wave variations due to load changes, by comparing
      wave statistical patterns via Principal Component Analysis (PCA). Each load
      scenario is projected to the PCA space by means of a baseline model and
      represented using the Q-statistical indices. Experimental validation of the
      proposed methodology is conducted on two specimens: (i) a 12.7 mm ( 1 / 2 " )
      diameter, 0.4 m length, AISI 1020 steel rod, and (ii) a 25.4 mm ( 1 " ) diameter,
      6m length, schedule 40, A-106, hollow cylinder. Specimen 1 was subjected to axial
      loads, meanwhile specimen 2 to flexion. In both cases, simultaneous longitudinal
      and flexural guided waves were generated via piezoelectric devices (PZTs) in a
      pitch-catch configuration. Experimental results show the feasibility of the
      approach and its potential use as in-situ continuous stress monitoring
      application.

PMID- 29194385
TI  - Improvement of High-Temperature Stability of Al2O3/Pt/ZnO/Al2O3 Film Electrode
      for SAW Devices by Using Al2O3 Barrier Layer.
AB  - In order to develop film electrodes for the surface acoustic wave (SAW) devices
      operating in harsh high-temperature environments, novel Al2O3/Pt/ZnO/Al2O3
      multilayered film electrodes were prepared by laser molecular beam epitaxy (LMBE)
      at 150  degrees C. The first Al2O3 layer was used as a barrier layer to prevent
      the diffusion of Ga, La, and Si atoms from the La3Ga5SiO14 (LGS) substrate to the
      film electrode and thus improved the crystalline quality of ZnO and Pt films. It
      was found that the resistance of the Al2O3/Pt/ZnO/Al2O3 electrode did not vary up
      to a temperature of 1150  degrees C, suggesting a high reliability of electrode
      under harsh high-temperature environments. The mechanism of the stable resistance
      of the Al2O3/Pt/ZnO/Al2O3 film electrodes at high temperature was investigated by
      analyzing its microstructure. The proposed Al2O3/Pt/ZnO/Al2O3 film electrode has
      great potential for application in high-temperature SAW devices.

PMID- 29194386
TI  - Hierarchical Control of Nitrite Respiration by Transcription Factors Encoded
      within Mobile Gene Clusters of Thermus thermophilus.
AB  - Denitrification in Thermus thermophilus is encoded by the nitrate respiration
      conjugative element (NCE) and nitrite and nitric oxide respiration (nic) gene
      clusters. A tight coordination of each cluster's expression is required to
      maximize anaerobic growth, and to avoid toxicity by intermediates, especially
      nitric oxides (NO). Here, we study the control of the nitrite reductases (Nir)
      and NO reductases (Nor) upon horizontal acquisition of the NCE and nic clusters
      by a formerly aerobic host. Expression of the nic promoters PnirS, PnirJ, and
      PnorC, depends on the oxygen sensor DnrS and on the DnrT protein, both NCE
      encoded. NsrR, a nic-encoded transcription factor with an iron-sulfur cluster, is
      also involved in Nir and Nor control. Deletion of nsrR decreased PnorC and PnirJ
      transcription, and activated PnirS under denitrification conditions, exhibiting a
      dual regulatory role never described before for members of the NsrR family. On
      the basis of these results, a regulatory hierarchy is proposed, in which under
      anoxia, there is a pre-activation of the nic promoters by DnrS and DnrT, and then
      NsrR leads to Nor induction and Nir repression, likely as a second stage of
      regulation that would require NO detection, thus avoiding accumulation of toxic
      levels of NO. The whole system appears to work in remarkable coordination to
      function only when the relevant nitrogen species are present inside the cell.

PMID- 29194387
TI  - Preparation and Characterization of Cabamazepine Cocrystal in Polymer Solution.
AB  - In this study, we attempted to prepare carbamazepine (CBZ) cocrystal through the
      solution method in ethanol-water solvent mixture (volume ratio 1:1) and polyvinyl
      pyrrolidone (PVP) solution. Nicotinamide (NIC) and saccharin (SAC) were selected
      as cocrystal coformers. Cocrystal screening products were characterized by
      Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry
      (DSC), and Powder X-ray Diffraction (PXRD) techniques. Characterization results
      show that in ethanol-water solvent mixture, pure CBZ-NIC cocrystal can be
      prepared, while CBZ-SAC cocrystal cannot be obtained. The addition of PVP can
      inhibit CBZ-NIC cocrystal formation and facilitate CBZ-SAC cocrystal formation.

PMID- 29194388
TI  - Antinociceptive Activity of Macaranga denticulata Muell. Arg. (Family:
      Euphorbiaceae): In Vivo and In Silico Studies.
AB  - Background: The present study was conducted to investigate the antinociceptive
      activity of methanol extract of Macaranga denticulata (Met.MD) in an animal
      model, followed by molecular docking analysis. Methods: Antinociceptive activity
      was determined by acetic acid-induced writhing and formalin-induced licking test
      in mice. Then, molecular docking study was performed to identify compounds having
      maximum activity against the COX-1 enzyme using Schrodinger Maestro (version
      10.1) to determine docking fitness. Results: A preliminary phytochemical analysis
      of Met.MD revealed that it contained alkaloids, carbohydrates, phenols,
      flavonoids, tannins, and terpenoids. Met.MD exhibited a dose-dependent and
      statistically significant antinociceptive activity in the acetic acid and
      formalin test at the doses of 200 and 400 mg/kg. In addition, our docking study
      showed that macarangin had the best fitness score of -5.81 with COX-1 enzyme
      among six major compounds of M. denticulata. Conclusions: Results of the present
      study confirmed the potential antinociceptive activity of M. denticulata leaf
      extract in both in vivo and in silico models.

PMID- 29194389
TI  - Variation in CYP2A6 Activity and Personalized Medicine.
AB  - The cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several clinically relevant
      substrates, including nicotine-the primary psychoactive component in cigarette
      smoke. The gene that encodes the CYP2A6 enzyme is highly polymorphic, resulting
      in extensive interindividual variation in CYP2A6 enzyme activity and the rate of
      metabolism of nicotine and other CYP2A6 substrates including cotinine, tegafur,
      letrozole, efavirenz, valproic acid, pilocarpine, artemisinin, artesunate, SM
      12502, caffeine, and tyrosol. CYP2A6 expression and activity are also impacted by
      non-genetic factors, including induction or inhibition by pharmacological,
      endogenous, and dietary substances, as well as age-related changes, or
      interactions with other hepatic enzymes, co-enzymes, and co-factors. As variation
      in CYP2A6 activity is associated with smoking behavior, smoking cessation,
      tobacco-related lung cancer risk, and with altered metabolism and resulting
      clinical responses for several therapeutics, CYP2A6 expression and enzyme
      activity is an important clinical consideration. This review will discuss sources
      of variation in CYP2A6 enzyme activity, with a focus on the impact of CYP2A6
      genetic variation on metabolism of the CYP2A6 substrates.

PMID- 29194390
TI  - Thyroid Disrupting Chemicals.
AB  - Endocrine disruptor compounds are exogenous agents able to interfere with a gland
      function, exerting their action across different functional passages, from the
      synthesis to the metabolism and binding to receptors of the hormone produced.
      Several issues, such as different levels and time of exposure and different
      action across different ages as well as gender, make the study of endocrine
      disruptors still a challenge. The thyroid is very sensitive to the action of
      disruptors, and considering the importance of a correct thyroid function for
      physical and cognitive functioning, addressing this topic should be considered a
      priority. In this review, we examined the most recent studies, many of them
      concentrating on maternal and child exposure, conducted to assess the impact of
      industrial chemicals which showed an influence on thyroid function. So far, the
      number of studies conducted on that topic is not sufficient to provide solid
      conclusions and lead to homogeneous guidelines. The lack of uniformity is
      certainly due to differences in areas and populations examined, the different
      conditions of exposures and the remarkable inter-subject variability.
      Nonetheless, the European Commission for Health and Food Safety is implementing
      recommendations to ensure that substances identified as endocrine disruptors will
      be withdrawn from the market.

PMID- 29194391
TI  - Impaired Osteogenesis of Disease-Specific Induced Pluripotent Stem Cells Derived
      from a CFC Syndrome Patient.
AB  - Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder caused by
      mutations in the extracellular signal-regulated kinase (ERK) signaling. However,
      little is known about how aberrant ERK signaling is associated with the defective
      bone development manifested in most CFC syndrome patients. In this study, induced
      pluripotent stem cells (iPSCs) were generated from dermal fibroblasts of a CFC
      syndrome patient having rapidly accelerated fibrosarcoma kinase B (BRAF) gain-of
      function mutation. CFC-iPSCs were differentiated into mesenchymal stem cells (CFC
      MSCs) and further induced to osteoblasts in vitro. The osteogenic defects of CFC
      MSCs were revealed by alkaline phosphatase activity assay, mineralization assay,
      quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting.
      Osteogenesis of CFC-MSCs was attenuated compared to wild-type (WT)-MSCs. In
      addition to activated ERK signaling, increased p-SMAD2 and decreased p-SMAD1 were
      observed in CFC-MSCs during osteogenesis. The defective osteogenesis of CFC-MSCs
      was rescued by inhibition of ERK signaling and SMAD2 signaling or activation of
      SMAD1 signaling. Importantly, activation of ERK signaling and SMAD2 signaling or
      inhibition of SMAD1 signaling recapitulated the impaired osteogenesis in WT-MSCs.
      Our findings indicate that SMAD2 signaling and SMAD1 signaling as well as ERK
      signaling are responsible for defective early bone development in CFC syndrome,
      providing a novel insight on the pathological mechanism and therapeutic targets.

PMID- 29194392
TI  - A Cluster Randomized Trial to Promote Healthy Menu Items for Children: The Kids'
      Choice Restaurant Program.
AB  - Evidence indicates that restaurant-based interventions have the potential to
      promote healthier purchasing and improve the nutrients consumed. This study adds
      to this body of research by reporting the results of a trial focused on promoting
      the sale of healthy child menu items in independently owned restaurants. Eight
      pair-matched restaurants that met the eligibility criteria were randomized to a
      menu-only versus a menu-plus intervention condition. Both of the conditions
      implemented new healthy child menu items and received support for implementation
      for eight weeks. The menu-plus condition also conducted a marketing campaign
      involving employee trainings and promotional materials. Process evaluation data
      captured intervention implementation. Sales of new and existing child menu items
      were tracked for 16 weeks. Results indicated that the interventions were
      implemented with moderate to high fidelity depending on the component. Sales of
      new healthy child menu items occurred immediately, but decreased during the post
      intervention period in both conditions. Sales of existing child menu items
      demonstrated a time by condition effect with restaurants in the menu-plus
      condition observing significant decreases and menu-only restaurants observing
      significant increases in sales of existing child menu items. Additional efforts
      are needed to inform sustainable methods for improving access to healthy foods
      and beverages in restaurants.

PMID- 29194393
TI  - Developing a Novel Parameter Estimation Method for Agent-Based Model in Immune
      System Simulation under the Framework of History Matching: A Case Study on
      Influenza A Virus Infection.
AB  - Since they can provide a natural and flexible description of nonlinear dynamic
      behavior of complex system, Agent-based models (ABM) have been commonly used for
      immune system simulation. However, it is crucial for ABM to obtain an appropriate
      estimation for the key parameters of the model by incorporating experimental
      data. In this paper, a systematic procedure for immune system simulation by
      integrating the ABM and regression method under the framework of history matching
      is developed. A novel parameter estimation method by incorporating the experiment
      data for the simulator ABM during the procedure is proposed. First, we employ ABM
      as simulator to simulate the immune system. Then, the dimension-reduced type
      generalized additive model (GAM) is employed to train a statistical regression
      model by using the input and output data of ABM and play a role as an emulator
      during history matching. Next, we reduce the input space of parameters by
      introducing an implausible measure to discard the implausible input values. At
      last, the estimation of model parameters is obtained using the particle swarm
      optimization algorithm (PSO) by fitting the experiment data among the non
      implausible input values. The real Influeza A Virus (IAV) data set is employed to
      demonstrate the performance of our proposed method, and the results show that the
      proposed method not only has good fitting and predicting accuracy, but it also
      owns favorable computational efficiency.

PMID- 29194394
TI  - Theoretical Study of ClOO + NO Reaction: Mechanism and Kinetics.
AB  - Theoretical investigations are performed on mechanism and kinetics of the
      reaction of halogen peroxy radical ClOO with NO radical. The electronic structure
      information for both of the singlet and triplet potential energy surfaces (PESs)
      is obtained at the MP2/6-311 + G(2df) level of theory, and the single-point
      energies are refined by the CCSD(T)/6-311 + G(2df) level. The rate constants for
      various product channels of the reaction in the pressure range of 1-7600 Torr are
      predicted. The main results are as follows: On the singlet surface, the addition
      elimination mechanism is the most important. First, the N atom of the NO radical
      can attack the O atom of the ClOO radical to form an energy-riched intermediate
      IM1 ClOONOtp (21.3 kcal/mol) barrierlessly, then IM1 could isomerizes to IM2
      ClOONOcp (22.1 kcal/mol) via a low energy barrier. Both IM1 and IM2 can
      dissociate to the primary product P1 ClNO + 1O2 and the secondary product P2 ClO
      + NO2. On the triplet surface, the direct Cl-abstraction reaction is the most
      feasible pathway. The Cl-abstraction can take place via a van der Waals complex,
      3IM1 ONClOO (4.1 kcal/mol), then it fragments readily to give P1' ClNO + 3O2 with
      a small barrier. The kinetic calculations show that at low temperatures, the
      singlet bimolecular product P1 is the primary product, while at high
      temperatures, the triplet product P1' becomes the primary one; only at high
      pressures and low temperatures, the unimolecular products IM1 and IM2 can be
      found with quite small yields. At experimentally measured temperature 213 K, ClNO
      is the primary product in the whole pressure range, which is consistent with the
      previous experiment. The present study may be useful for further experimental
      studies for the title reaction.

PMID- 29194395
TI  - Efficient Removal of Tetracycline from Aqueous Media with a Fe3O4
      Nanoparticles@graphene Oxide Nanosheets Assembly.
AB  - A readily separated composite was prepared via direct assembly of Fe3O4 magnetic
      nanoparticles onto the surface of graphene oxide (GO) (labeled as Fe3O4@GO) and
      used as an adsorbent for the removal of tetracycline (TC) from wastewater. The
      effects of external environmental conditions, such as pH, ionic strength, humic
      acid (HA), TC concentration, and temperature, on the adsorption process were
      studied. The adsorption data were analyzed by kinetics and isothermal models. The
      results show that the Fe3O4@GO composite has excellent sorptive properties and
      can efficiently remove TC. At low pH, the adsorption capacity of Fe3O4@GO toward
      TC decreases slowly with increasing pH value, while the adsorption capacity
      decreases rapidly at higher pH values. The ionic strength has insignificant
      effect on TC adsorption. The presence of HA affects the affinity of Fe3O4@GO to
      TC. The pseudo-second-order kinetics model and Langmuir model fit the adsorption
      data well. When the initial concentration of TC is 100 mg/L, a slow adsorption
      process dominates. Film diffusion is the rate limiting step of the adsorption.
      Importantly, Fe3O4@GO has good regeneration performance. The above results are of
      great significance to promote the application of Fe3O4@GO in the treatment of
      antibiotic wastewater.

PMID- 29194396
TI  - Aquaporins during Pregnancy: Their Function and Significance.
AB  - Water is the major component of cells and tissues, and the movement of water
      across the cell membrane is a fundamental property of life. Until the discovery
      of the first water channel, aquaporin, it was long assumed that the transport of
      water was due to simple diffusion through the lipid bilayer membrane that
      encloses cells. Aquaporin (AQP) molecules were first discovered in the human
      uterus in 1994, and since then several studies have investigated these channels
      in the female reproductive system. The expressions of AQPs have been proven in
      the reproductive system. Their levels are altered during the implantation
      process, both in the uterus and the fetal cells, and participate in the control
      of the flow of amniotic fluid. They seem to be very important for the normal
      placental functions. AQPs are present during parturition, participating in the
      control of pregnant myometrial contractions and cervical ripening. However, most
      of the physiological and regulatory roles of AQPs are not clarified in the
      reproductive tract. Furthermore, no satisfactory knowledge is available about
      their sensitivities to different drugs. AQP-selective ligands may contribute to
      the development of new drug candidates and the therapy of several reproductive
      disorders.

PMID- 29194397
TI  - Comparative Evaluation of Chemical Profiles of Pyrrosiae Folium Originating from
      Three Pyrrosia Species by HPLC-DAD Combined with Multivariate Statistical
      Analysis.
AB  - Pyrrosiae Folium (PF) is a commonly used Chinese herb medicine originating from
      three Pyrrosia species for the treatment of urinary infection and urolithiasis.
      According to Chinese medicine practice, different specie origins led to some
      variations in the therapeutic effects of PF. To ensure the safety and efficacy of
      PF in clinical practice, it is necessary to establish a reliable and integrative
      method to distinguish PF occurring from the three species. In the present paper,
      a HPLC-DAD method was developed and applied to simultaneously analyze five major
      compounds in PF. Afterwards, multivariate statistical analyses including
      principal component analysis (PCA) and partial least squares discriminant
      analysis (PLS-DA) were applied for specie discrimination and integrative quality
      evaluation based on quantitative data. The chemical determination and pattern
      recognition results of 35 batches of PF samples indicated that PF samples from
      three species showed different chemical profiles and could be discriminated
      clearly. In conclusion, the present method is rapid and reliable for the quality
      assessment and species discrimination of PF.

PMID- 29194399
TI  - QNA-Based Prediction of Sites of Metabolism.
AB  - Metabolism of xenobiotics (Greek xenos: exogenous substances) plays an essential
      role in the prediction of biological activity and testing for the subsequent
      research and development of new drug candidates. Integration of various methods
      and techniques using different computational and experimental approaches is one
      of the keys to a successful metabolism prediction. While multiple structure-based
      and ligand-based approaches to metabolism prediction exist, the most important
      problem arises at the first stage of metabolism prediction: detection of the
      sites of metabolism (SOMs). In this paper, we describe the application of
      Quantitative Neighborhoods of Atoms (QNA) descriptors for prediction of the SOMs
      using potential function method, as well as several different machine learning
      techniques: naive Bayes, random forest classifier, multilayer perceptron with
      back propagation and convolutional neural networks, and deep neural networks.

PMID- 29194398
TI  - Synthesis of Rhizobial Exopolysaccharides and Their Importance for Symbiosis with
      Legume Plants.
AB  - Rhizobia dwell and multiply in the soil and represent a unique group of bacteria
      able to enter into a symbiotic interaction with plants from the Fabaceae family
      and fix atmospheric nitrogen inside de novo created plant organs, called nodules.
      One of the key determinants of the successful interaction between these bacteria
      and plants are exopolysaccharides, which represent species-specific homo- and
      heteropolymers of different carbohydrate units frequently decorated by non
      carbohydrate substituents. Exopolysaccharides are typically built from repeat
      units assembled by the Wzx/Wzy-dependent pathway, where individual subunits are
      synthesized in conjunction with the lipid anchor undecaprenylphosphate (und-PP),
      due to the activity of glycosyltransferases. Complete oligosaccharide repeat
      units are transferred to the periplasmic space by the activity of the Wzx
      flippase, and, while still being anchored in the membrane, they are joined by the
      polymerase Wzy. Here we have focused on the genetic control over the process of
      exopolysaccharides (EPS) biosynthesis in rhizobia, with emphasis put on the
      recent advancements in understanding the mode of action of the key proteins
      operating in the pathway. A role played by exopolysaccharide in Rhizobium-legume
      symbiosis, including recent data confirming the signaling function of EPS, is
      also discussed.

PMID- 29194400
TI  - Evidence of Biomass Smoke Exposure as a Causative Factor for the Development of
      COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive disease of the
      lungs characterised by chronic inflammation, obstruction of airways, and
      destruction of the parenchyma (emphysema). These changes gradually impair lung
      function and prevent normal breathing. In 2002, COPD was the fifth leading cause
      of death, and is estimated by the World Health Organisation (WHO) to become the
      third by 2020. Cigarette smokers are thought to be the most at risk of developing
      COPD. However, recent studies have shown that people with life-long exposure to
      biomass smoke are also at high risk of developing COPD. Most common in developing
      countries, biomass fuels such as wood and coal are used for cooking and heating
      indoors on a daily basis. Women and children have the highest amounts of
      exposures and are therefore more likely to develop the disease. Despite
      epidemiological studies providing evidence of the causative relationship between
      biomass smoke and COPD, there are still limited mechanistic studies on how
      biomass smoke causes, and contributes to the progression of COPD. This review
      will focus upon why biomass fuels are used, and their relationship to COPD. It
      will also suggest methodological approaches to model biomass exposure in vitro
      and in vivo.

PMID- 29194402
TI  - Nutrition in the First 1000 Days: Ten Practices to Minimize Obesity Emerging from
      Published Science.
AB  - The prevalence of childhood overweight and obesity has increased in most
      countries the last decades. Considering this in a simplistic way, we can say that
      obesity is the result of an imbalance between energy intake and energy
      expenditure. Moreover, the environment from conception to childhood could
      influence the child's future health. The first 1000 days of life start with
      woman's pregnancy, and offer a unique window of opportunity to contribute to
      obesity prevention. In light of the actual literature, the aim of our article is
      to discuss a proposal of 10 good practices to minimize obesity in the first 1000
      days emerging from published science. (1) Both the mother's and the father's
      behaviors are important. A balanced diet with appropriate fat and protein intake,
      and favoring fruits and vegetables, is recommended for both parents during the
      conception period and pregnancy. Furthermore, overweight/obese women who are
      planning to become pregnant should reduce their weight before conception. (2)
      During pregnancy, at birth, and during early life, body composition measurements
      are crucial to monitor the baby's growth. (3) Exclusive breastfeeding is
      recommended at the beginning of life until six months of age. (4) Four to six
      months of age is the optimal window to introduce complementary feeding. Until one
      year of age, breast milk or follow-on/commercial formula is the main recommended
      feeding source, and cow's milk should be avoided until one year of age. (5) Fruit
      and vegetable introduction should begin early. Daily variety, diversity in a
      meal, and repeated exposure to the food, up to eight times, are efficient
      strategies to increase acceptance of food not well accepted at first. There is no
      need to add sugar, salt, or sugary fluids to the diet. (6) Respect the child's
      appetite and avoid coercive "clean your plate" feeding practices. Adapt the
      portion of food and don't use food as reward for good behavior. (7) Limit animal
      protein intake in early life to reduce the risk of an early adiposity rebound.
      Growing-up milk for children between one and three years of age should be
      preferred to cow's milk, in order to limit intake and meet essential fatty acid
      and iron needs. (8) The intake of adequate fat containing essential fatty acids
      should be promoted. (9) Parents should be role models when feeding, with TV and
      other screens turned-off during meals. (10) Preventive interventions consisting
      of promoting physical activity and sufficient time dedicated to sleep should be
      employed. In fact, short sleep duration may be associated with increased risk of
      developing obesity. Based on literature reviews, and given the suggestions
      described in this manuscript, concerted public health efforts are needed to
      achieve the healthy objectives for obesity and nutrition, and to fight the
      childhood obesity epidemic.

PMID- 29194403
TI  - Inhibitors of Serine Proteases from a Microcystis sp. Bloom Material Collected
      from Timurim Reservoir, Israel.
AB  - Two new natural products, micropeptin TR1058 (1) and aeruginosin TR642 (2), were
      isolated from the hydrophilic extract of bloom material of Microcystis sp.
      collected from the Timurim water reservoir in Israel. The structures of compounds
      1 and 2 were determined using 1D and 2D NMR spectroscopy and HR ESI MS and MS/MS
      techniques. Micropeptin TR1058 (1) was extremely unstable under the isolation
      conditions, and several degradation products were identified. NMR analysis of
      aeruginosin TR642 (2) revealed a mixture of eight isomers, and elucidation of its
      structure was challenging. Aeruginosin TR642 contains a 4,5-didehydroaraginal
      subunit that has not been described before. Micropeptin TR1058 (1) inhibited
      chymotrypsin with an IC50 of 6.78 uM, and aeruginosin TR642 (2) inhibited trypsin
      and thrombin with inhibition concentration (IC50) values of 3.80 and 0.85 uM,
      respectively. The structures and biological activities of the new compounds are
      discussed.

PMID- 29194401
TI  - Drug Resistance Driven by Cancer Stem Cells and Their Niche.
AB  - Drug resistance represents one of the greatest challenges in cancer treatment.
      Cancer stem cells (CSCs), a subset of cells within the tumor with the potential
      for self-renewal, differentiation and tumorigenicity, are thought to be the major
      cause of cancer therapy failure due to their considerable chemo- and
      radioresistance, resulting in tumor recurrence and eventually metastasis. CSCs
      are situated in a specialized microenvironment termed the niche, mainly composed
      of fibroblasts and endothelial, mesenchymal and immune cells, which also play
      pivotal roles in drug resistance. These neighboring cells promote the molecular
      signaling pathways required for CSC maintenance and survival and also trigger
      endogenous drug resistance in CSCs. In addition, tumor niche components such as
      the extracellular matrix also physically shelter CSCs from therapeutic agents.
      Interestingly, CSCs contribute directly to the niche in a bilateral feedback loop
      manner. Here, we review the recent advances in the study of CSCs, the niche and
      especially their collective contribution to resistance, since increasingly
      studies suggest that this interaction should be considered as a target for
      therapeutic strategies.

PMID- 29194405
TI  - Quantitative Properties of the Macro Supply and Demand Structure for Care
      Facilities for Elderly in Japan.
AB  - As the Asian country with the most aged population, Japan, has been modifying its
      social welfare system. In 2000, the Japanese social care vision turned towards
      meeting the elderly's care needs in their own homes with proper formal care
      services. This study aims to understand the quantitative properties of the macro
      supply and demand structure for facilities for the elderly who require support or
      long-term care throughout Japan and present them as index values. Additionally,
      this study compares the targets for establishing long-term care facilities set by
      Japan's Ministry of Health, Labor and Welfare for 2025. In 2014, approximately
      90% of all the people who were certified as requiring support and long-term care
      and those receiving preventive long-term care or long-term care services, were 75
      years or older. The target increases in the number of established facilities by
      2025 (for the 75-years-or-older population) were calculated to be 3.3% for
      nursing homes; 2.71% for long-term-care health facilities; 1.7% for group living
      facilities; and, 1.84% for community-based multi-care facilities. It was revealed
      that the establishment targets for 2025 also increase over current projections
      with the expected increase of the absolute number of users of group living
      facilities and community-based multi-care facilities. On the other hand, the
      establishment target for nursing homes remains almost the same as the current
      projection, whereas that for long-term-care health facilities decreases. These
      changes of facility ratios reveal that the Japanese social care system is
      shifting to realize 'Ageing in Place'. When considering households' tendencies,
      the target ratios for established facilities are expected to be applied to the
      other countries in Asia.

PMID- 29194404
TI  - Recent Advances in our Understanding of Tocopherol Biosynthesis in Plants: An
      Overview of Key Genes, Functions, and Breeding of Vitamin E Improved Crops.
AB  - Tocopherols, together with tocotrienols and plastochromanols belong to a group of
      lipophilic compounds also called tocochromanols or vitamin E. Considered to be
      one of the most powerful antioxidants, tocochromanols are solely synthesized by
      photosynthetic organisms including plants, algae, and cyanobacteria and,
      therefore, are an essential component in the human diet. Tocochromanols potent
      antioxidative properties are due to their ability to interact with
      polyunsaturated acyl groups and scavenge lipid peroxyl radicals and quench
      reactive oxygen species (ROS), thus protecting fatty acids from lipid
      peroxidation. In the plant model species Arabidopsis thaliana, the required genes
      for tocopherol biosynthesis and functional roles of tocopherols were elucidated
      in mutant and transgenic plants. Recent research efforts have led to new outcomes
      for the vitamin E biosynthetic and related pathways, and new possible
      alternatives for the biofortification of important crops have been suggested.
      Here, we review 30 years of research on tocopherols in model and crop species,
      with emphasis on the improvement of vitamin E content using transgenic approaches
      and classical breeding. We will discuss future prospects to further improve the
      nutritional value of our food.

PMID- 29194406
TI  - Whole Body and CNS Biodistribution of rhHNS in Cynomolgus Monkeys after
      Intrathecal Lumbar Administration: Treatment Implications for Patients with MPS
      IIIA.
AB  - Mucopolysaccharidosis III type A (MPS IIIA; Sanfilippo syndrome), a genetic
      lysosomal disorder causing a deficiency of heparan N-sulfatase (HNS), leads to
      progressive cognitive decline from an early age. An effective enzyme replacement
      therapy (ERT) for MPS IIIA requires central nervous system (CNS) biodistribution.
      Recombinant human heparan N-sulfatase (rhHNS), an investigatory ERT for MPS IIIA,
      has been formulated for intrathecal (IT) administration since intravenous (IV)
      administration cannot cross the blood brain barrier (BBB) in sufficient amounts
      to have a therapeutic effect. In this study, systemic and CNS distribution of
      rhHNS in cynomolgus monkeys following IV and IT administration was evaluated by
      quantitation of rhHNS in serum, cerebral spinal fluid (CSF) and various tissues,
      and positron emission tomography (PET) imaging of live animals. Following IV
      administration, rhHNS levels were low to non-detectable in the CSF, and systemic
      clearance was rapid (<=2 h). With IT administration, rhHNS was observable in CNS
      tissues in <=1 h, with varying Tmax (1-24 h). Appreciable systemic distribution
      was observed up to 7 days. This provides evidence that in this animal model,
      intrathecal administration of rhHNS delivers the replacement enzyme to
      therapeutically relevant tissues for the treatment of Sanfilippo Syndrome type A.
      Penetration into grey matter and cortex was 3-4 times greater than concentrations
      in white matter and deeper parenchymal regions, suggesting some limitations of
      this ERT strategy.

PMID- 29194407
TI  - Adaptive Residual Interpolation for Color and Multispectral Image Demosaicking.
AB  - Color image demosaicking for the Bayer color filter array is an essential image
      processing operation for acquiring high-quality color images. Recently, residual
      interpolation (RI)-based algorithms have demonstrated superior demosaicking
      performance over conventional color difference interpolation-based algorithms. In
      this paper, we propose adaptive residual interpolation (ARI) that improves
      existing RI-based algorithms by adaptively combining two RI-based algorithms and
      selecting a suitable iteration number at each pixel. These are performed based on
      a unified criterion that evaluates the validity of an RI-based algorithm.
      Experimental comparisons using standard color image datasets demonstrate that ARI
      can improve existing RI-based algorithms by more than 0.6 dB in the color peak
      signal-to-noise ratio and can outperform state-of-the-art algorithms based on
      training images. We further extend ARI for a multispectral filter array, in which
      more than three spectral bands are arrayed, and demonstrate that ARI can achieve
      state-of-the-art performance also for the task of multispectral image
      demosaicking.

PMID- 29194408
TI  - Exposure to Night-Time Traffic Noise, Melatonin-Regulating Gene Variants and
      Change in Glycemia in Adults.
AB  - Traffic noise has been linked to diabetes, with limited understanding of its
      mechanisms. We hypothesize that night-time road traffic noise (RTN) may impair
      glucose homeostasis through circadian rhythm disturbances. We prospectively
      investigated the relationship between residential night-time RTN and subsequent
      eight-year change in glycosylated hemoglobin (DeltaHbA1c) in 3350 participants of
      the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults
      (SAPALDIA), adjusting for diabetes risk factors and air pollution levels. Annual
      average RTN (Lnight) was assigned to participants in 2001 using validated Swiss
      noise models. HbA1c was measured in 2002 and 2011 using liquid chromatography. We
      applied mixed linear models to explore RTN-DeltaHbA1c association and its
      modification by a genetic risk score of six common circadian-related MTNR1B
      variants (MGRS). A 10 dB difference in RTN was associated with a 0.02% (0.003
      0.04%) increase in mean DeltaHbA1c in 2142 non-movers. RTN-DeltaHbA1c association
      was modified by MGRS among diabetic participants (Pinteraction = 0.001). A
      similar trend in non-diabetic participants was non-significant. Among the single
      variants, we observed strongest interactions with rs10830963, an acknowledged
      diabetes risk variant also implicated in melatonin profile dysregulation. Night
      time RTN may impair glycemic control, especially in diabetic individuals, through
      circadian rhythm disturbances. Experimental sleep studies are needed to test
      whether noise control may help individuals to attain optimal glycemic levels.

PMID- 29194411
TI  - Incentive Policy Options for Product Remanufacturing: Subsidizing Donations or
      Resales?
AB  - Remanufactured products offer better environmental benefits, and governments
      encourage manufacturers to remanufacture through various subsidy policies. This
      practice has shown that, in addition to product sales, remanufactured product can
      also achieve its value through social donation. Based on the remanufactured
      product value realization approaches, governments provide two kinds of incentive
      policies, which are remanufactured product sales subsidies and remanufactured
      product donation subsidies. This paper constructs a two-stage Stackelberg game
      model including a government and a manufacturer under two different policies,
      which can be solved by backward induction. By comparing the optimal decision of
      the two policies, our results show that, compared with the remanufacturing sales
      subsidy, donation subsidy weakens the cannibalization of remanufactured products
      for new products and increases the quantity of new products. It reduces the sales
      quantity of remanufactured products, but increases their total quantity. Under
      certain conditions of low subsidy, the manufacturer adopting sales subsidy
      provides better economic and environmental benefits. Under certain conditions of
      high subsidy, the manufacturer adopting donation subsidy offers better economic
      and environmental benefits. When untreated product environmental impact is large
      enough, donation subsidy policy has a better social welfare. Otherwise, the
      choice of social welfare of these two different policies depends on the social
      impact of remanufactured product donated.

PMID- 29194409
TI  - Auxin Information Processing; Partners and Interactions beyond the Usual
      Suspects.
AB  - Auxin plays a major role in a variety of processes involved in plant
      developmental patterning and its adaptation to environmental conditions.
      Therefore, an important question is how specificity in auxin signalling is
      achieved, that is, how a single signalling molecule can carry so many different
      types of information. In recent years, many studies on auxin specificity have
      been published, unravelling increasingly more details on differential auxin
      sensitivity, expression domains and downstream partners of the auxin receptors
      (transport inhibitor response 1 (TIR1) and other auxin signaling F-box proteins
      (AFB)), transcriptional repressors that are degraded in response to auxin
      (AUX/IAA) and downstream auxin response factors (ARF) that together constitute
      the plant's major auxin response pathways. These data are critical to explain
      how, in the same cells, different auxin levels may trigger different responses,
      as well as how in different spatial or temporal contexts similar auxin signals
      converge to different responses. However, these insights do not yet answer more
      complex questions regarding auxin specificity. As an example, they leave open the
      question of how similar sized auxin changes at similar locations result in
      different responses depending on the duration and spatial extent of the
      fluctuation in auxin levels. Similarly, it leaves unanswered how, in the case of
      certain tropisms, small differences in signal strength at both sides of a plant
      organ are converted into an instructive auxin asymmetry that enables a robust
      tropic response. Finally, it does not explain how, in certain cases,
      substantially different auxin levels become translated into similar cellular
      responses, while in other cases similar auxin levels, even when combined with
      similar auxin response machinery, may trigger different responses. In this
      review, we illustrate how considering the regulatory networks and contexts in
      which auxin signalling takes place helps answer these types of fundamental
      questions.

PMID- 29194410
TI  - Multi Component Reactions under Increased Pressure: On the Mechanism of Formation
      of Pyridazino[5,4,3-de][1,6]naphthyridine Derivatives by the Reaction of
      Malononitrile, Aldehydes and 2-Oxoglyoxalarylhydrazones in Q-Tubes.
AB  - Efficient synthesis of phenanthridin-6(5H)-one derivatives 12a-n in a four
      component reaction of aldehyde hydrazone, aromatic aldehydes and malononitrile in
      Q-Tubes is reported. The results showed that the methodology has the advantage of
      being a one-pot synthesis of tricyclic systems in good yields. Potential routes
      leading to formation of compounds 12 are discussed. The structures of the
      synthesized compounds could be unequivocally established via X-ray crystal
      structure determination and spectroscopic methods.

PMID- 29194413
TI  - An Interface for Biomedical Big Data Processing on the Tianhe-2 Supercomputer.
AB  - Big data, cloud computing, and high-performance computing (HPC) are at the verge
      of convergence. Cloud computing is already playing an active part in big data
      processing with the help of big data frameworks like Hadoop and Spark. The recent
      upsurge of high-performance computing in China provides extra possibilities and
      capacity to address the challenges associated with big data. In this paper, we
      propose Orion-a big data interface on the Tianhe-2 supercomputer-to enable big
      data applications to run on Tianhe-2 via a single command or a shell script.
      Orion supports multiple users, and each user can launch multiple tasks. It
      minimizes the effort needed to initiate big data applications on the Tianhe-2
      supercomputer via automated configuration. Orion follows the "allocate-when
      needed" paradigm, and it avoids the idle occupation of computational resources.
      We tested the utility and performance of Orion using a big genomic dataset and
      achieved a satisfactory performance on Tianhe-2 with very few modifications to
      existing applications that were implemented in Hadoop/Spark. In summary, Orion
      provides a practical and economical interface for big data processing on Tianhe
      2.

PMID- 29194412
TI  - A New Dihydrochromone Dimer and Other Secondary Metabolites from Cultures of the
      Marine Sponge-Associated Fungi Neosartorya fennelliae KUFA 0811 and Neosartorya
      tsunodae KUFC 9213.
AB  - A previously unreported dihydrochromone dimer, paecilin E (1), was isolated,
      together with eleven known compounds: beta-sitostenone, ergosta-4,6,8 (14), 22
      tetraen-3-one, cyathisterone, byssochlamic acid, dehydromevalonic acid lactone,
      chevalone B, aszonalenin, dankasterone A (2), helvolic acid, secalonic acid A and
      fellutanine A, from the culture filtrate extract of the marine sponge-associated
      fungus Neosartorya fennelliae KUFA 0811. Nine previously reported metabolites,
      including a chromanol derivative (3), (3beta, 5alpha, 22E), 3,5-dihydroxyergosta
      7,22-dien-6-one (4), byssochlamic acid, hopan-3beta,22-diol, chevalone C,
      sartorypyrone B, helvolic acid, lumichrome and the alkaloid harmane were isolated
      from the culture of the marine-sponge associated fungus Neosartorya tsunodae KUFC
      9213. Paecilin E (1), dankasterone A (2), a chromanol derivative (3), (3beta,
      5alpha, 22E)-3,5-dihydroxyergosta-7,22-dien-6-one (4), hopan-3beta,22-diol (5),
      lumichrome (6), and harmane (7) were tested for their antibacterial activity
      against Gram-positive and Gram-negative reference and multidrug-resistant strains
      isolated from the environment. While paecilin E (1) was active against S. aureus
      ATCC 29213 and E. faecalis ATCC 29212, dankastetrone A (2) was only effective
      against E. faecalis ATCC 29212 and the multidrug-resistant VRE E. faecalis
      A5/102. Both compounds neither inhibit biofilm mass production in any of the
      strains at the concentrations tested nor exhibit synergistic association with
      antibiotics.

PMID- 29194414
TI  - Marked Object Recognition Multitouch Screen Printed Touchpad for Interactive
      Applications.
AB  - The market for interactive platforms is rapidly growing, and touchscreens have
      been incorporated in an increasing number of devices. Thus, the area of smart
      objects and devices is strongly increasing by adding interactive touch and
      multimedia content, leading to new uses and capabilities. In this work, a
      flexible screen printed sensor matrix is fabricated based on silver ink in a
      polyethylene terephthalate (PET) substrate. Diamond shaped capacitive electrodes
      coupled with conventional capacitive reading electronics enables fabrication of a
      highly functional capacitive touchpad, and also allows for the identification of
      marked objects. For the latter, the capacitive signatures are identified by
      intersecting points and distances between them. Thus, this work demonstrates the
      applicability of a low cost method using royalty-free geometries and technologies
      for the development of flexible multitouch touchpads for the implementation of
      interactive and object recognition applications.

PMID- 29194415
TI  - Efficient Background Segmentation and Seed Point Generation for a Single-Shot
      Stereo System.
AB  - Single-shot stereo 3D shape measurement is becoming more popular due to its
      advantages of noise robustness and short acquisition period. One of the key
      problems is stereo matching, which is related to the efficiency of background
      segmentation and seed point generation, etc. In this paper, a more efficient and
      automated matching algorithm based on digital image correlation (DIC) is
      proposed. The standard deviation of image gradients and an adaptive threshold are
      employed to segment the background. Scale-invariant feature transform (SIFT)
      based feature matching and two-dimensional triangulation are combined to estimate
      accurate initial parameters for seed point generation. The efficiency of
      background segmentation and seed point generation, as well as the measuring
      precision, are evaluated by experimental simulation and real tests. Experimental
      results show that the average segmentation time for an image with a resolution of
      1280 * 960 pixels is 240 milliseconds. The efficiency of seed point generation is
      verified to be high with different convergence criteria.

PMID- 29194416
TI  - Melatonin Pharmacokinetics Following Oral Administration in Preterm Neonates.
AB  - Melatonin possesses potential efficacy in perinatal brain injuries, and has been
      proposed as adjunctive pharmacological therapy in combination with hypothermia in
      the clinical setting. However, the pharmacokinetics of melatonin in preterm and
      term newborns is still unknown. The aim of this study was to analyze the
      pharmacokinetics of melatonin after intragastric administration in preterm
      infants. Preterm newborns were enrolled 24-72 h after birth, and randomly
      assigned to three groups receiving a single bolus of 0.5 mg.kg-1 melatonin, or 3
      boluses of 1 or 5 mg.kg-1 of melatonin at 24-h intervals. Blood samples were
      collected before and at selective times after melatonin administration. The half
      life of melatonin in plasma ranged from 7.98 to 10.94 h, and the area under the
      curve (AUC) from 10.48 to 118.17 ug.mL-1.h-1. Our results indicate a different
      pharmacokinetic profile in premature newborns, compared to adults and
      experimental animals. The high peak plasma concentrations and the long half-life
      indicate that in the neonatal clinical setting, it is possible to obtain and
      maintain high serum concentrations using a single administration of melatonin
      repeated every 12/24 h.

PMID- 29194418
TI  - Controlled Synthesis of Monodisperse Hexagonal NaYF4:Yb/Er Nanocrystals with
      Ultrasmall Size and Enhanced Upconversion Luminescence.
AB  - The ability to synthesize upconversion nanocrystals (UCNCs) with tailored
      upconversion luminescence and controlled size is of great importance for
      biophotonic applications. However, until now, limited success has been met to
      prepare bright, ultrasmall, and monodispersed beta-NaYF4:Yb3+/Er3+ UCNCs. In this
      work, we report on a synthetic method to produce monodisperse hexagonal
      NaYF4:Yb3+/Er3+ nanocrystals of ultrasmall size (5.4 nm) through a precise
      control of the reaction temperature and the ratio of Na+/Ln3+/F-. We determined
      the optimum activator concentration of Er3+ to be 6.5 mol % for these UCNCs,
      yielding about a 5-fold higher upconversion luminescence (UCL) intensity than the
      commonly used formula of NaYF4:30% Yb3+/2% Er3+. Moreover, a thin epitaxial shell
      (thickness, 1.9 nm) of NaLnF4 (Ln = Y, Gd, Lu) was grown onto these ultrasmall
      NaYF4:Yb3+/Er3+ NCs, enhancing its UCL by about 85-, 70- and 50-fold,
      respectively. The achieved sub-10-nm core and core-shell hexagonal
      NaYF4:Yb3+/Er3+ UCNCs with enhanced UCL have strong potential applications in
      bioapplications such as bioimaging and biosensing.

PMID- 29194417
TI  - Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging in the
      Study of Gastric Cancer: A Mini Review.
AB  - Gastric cancer (GC) is one of the leading causes of cancer-related deaths
      worldwide and the disease outcome commonly depends upon the tumour stage at the
      time of diagnosis. However, this cancer can often be asymptomatic during the
      early stages and remain undetected until the later stages of tumour development,
      having a significant impact on patient prognosis. However, our comprehension of
      the mechanisms underlying the development of gastric malignancies is still
      lacking. For these reasons, the search for new diagnostic and prognostic markers
      for gastric cancer is an ongoing pursuit. Modern mass spectrometry imaging (MSI)
      techniques, in particular matrix-assisted laser desorption/ionisation (MALDI),
      have emerged as a plausible tool in clinical pathology as a whole. More
      specifically, MALDI-MSI is being increasingly employed in the study of gastric
      cancer and has already elucidated some important disease checkpoints that may
      help us to better understand the molecular mechanisms underpinning this
      aggressive cancer. Here we report the state of the art of MALDI-MSI approaches,
      ranging from sample preparation to statistical analysis, and provide a complete
      review of the key findings that have been reported in the literature thus far.

PMID- 29194420
TI  - Early Detection and Intervention of ASD: A European Overview.
AB  - Over the last several years there has been an increasing focus on early detection
      of Autism Spectrum Disorder (ASD), not only from the scientific field but also
      from professional associations and public health systems all across Europe. Not
      surprisingly, in order to offer better services and quality of life for both
      children with ASD and their families, different screening procedures and tools
      have been developed for early assessment and intervention. However, current
      evidence is needed for healthcare providers and policy makers to be able to
      implement specific measures and increase autism awareness in European
      communities. The general aim of this review is to address the latest and most
      relevant issues related to early detection and treatments. The specific
      objectives are (1) analyse the impact, describing advantages and drawbacks, of
      screening procedures based on standardized tests, surveillance programmes, or
      other observational measures; and (2) provide a European framework of early
      intervention programmes and practices and what has been learnt from implementing
      them in public or private settings. This analysis is then discussed and best
      practices are suggested to help professionals, health systems and policy makers
      to improve their local procedures or to develop new proposals for early detection
      and intervention programmes.

PMID- 29194421
TI  - Comparative Studies on Ultraviolet-Light-Derived Photoresponse Properties of ZnO,
      AZO, and GZO Transparent Semiconductor Thin Films.
AB  - ZnO, Al-doped ZnO (AZO), and Ga-doped ZnO (GZO) semiconductor thin films were
      deposited on glass substrates via a sol-gel spin-coating process for application
      in a photoconductive ultraviolet (UV) detector. The doping concentrations of Al
      and Ga were 1.0 at % in the precursor solutions. In this study, the
      microstructural features and the optical and electrical properties of sol-gel
      derived ZnO, AZO, and GZO thin films were compared, and the performance of ZnO
      based UV photodetectors under ultraviolet A (UVA) light were measured.
      Experimental results confirmed the synthesis of single-phase nanocrystalline ZnO
      based thin films and the successful substitution of Al and Ga into Zn sites in
      ZnO crystals. The results also demonstrated that the optical transmittance and
      electrical properties of ZnO thin films could be improved by Al and Ga doping. UV
      photodetectors based on ZnO-based thin films, having a metal-semiconductor-metal
      (MSM) configuration, were fabricated with Al inter-digitated electrodes. All
      photodetectors showed an ohmic nature between semiconductor and electrode
      contacts and exhibited a sharp increase in photocurrent under illumination with
      UVA light. We found that the MSM UV photodetector based on the GZO semiconductor
      thin film exhibited the best UV response (IUVA/Idark) of 73.3 and the highest
      photocurrent responsivity of 46.2 A/W under UVA light (power density ~0.825
      mW/cm2) at 5 V bias.

PMID- 29194419
TI  - The Interplay between Natural Killer Cells and Human Herpesvirus-6.
AB  - Human Herpesvirus 6 (HHV-6) is a set of two closely related herpes viruses known
      as HHV-6A and HHV-6B. Both are lymphotropic viruses that establish latency in the
      host. The ability to evade the immune responses of effector cells is likely a
      major factor contributing to the development of a persistent HHV-6A/B
      (collectively termed HHV-6) infection. Natural killer (NK) cells are lymphocytes
      that, along with neutrophils and monocytes/macrophages, participate in the
      critical innate immune response during viral infections, but can also mediate the
      antigen-specific memory responses generally associated with adaptive immunity. NK
      cells compose the first barrier that viruses must break through to continue
      replication and dissemination, and a weak NK cell response may predispose an
      individual to chronic viral infections. Both HHV-6A and HHV-6B can interfere with
      NK cell-mediated anti-viral responses but the mechanisms by which each of these
      viruses affect NK cell activity differs. In this review, we will explore the
      nuanced relationships between the two viruses and NK cells, discussing, in
      addition, relevant disease associations.

PMID- 29194422
TI  - Food and Nutrient Intake and Nutrient Sources in 1-Year-Old Infants in Finland: A
      Cross-Sectional Analysis.
AB  - The infant diet has short- and long-term health consequences. Updated data
      regarding the dietary intake of Finnish infants are lacking. The objectives of
      this study were to describe infant food and nutrient intake and to identify food
      sources of the nutrients. Altogether, 739 healthy infants were studied. Dietary
      intake and breastfeeding frequency were assessed with a three-day food record at
      1 year of age. Dietary intake was calculated separately for non-breastfed and
      breastfed infants. One-third (36%) of the infants were partially breastfed and
      95% consumed mass-produced baby foods. The infants' diet consisted mainly of
      infant formula, dairy milk, porridges, fruit and berry foods, and meat dishes.
      The mean vegetable, fruit and berry consumption was 199 g/day. Most nutrient
      intakes were adequate except for fat, linoleic acid, vitamin D and iron from
      food. Mean sucrose intake, as a percentage of total energy intake (E%), was 5-6
      E%. High protein intake (>20 E%) was observed in 19% of non-breastfed infants.
      Overall, the infants' diet was favorable since vegetable and fruit consumption
      was reasonably high and nutrient intake was mostly adequate. However, the fat
      intake was lower, and protein intake higher than recommended. Increasing the
      consumption of vegetable oils and reducing the intake of red meat and dairy milk
      may further improve the diet of 1-year-olds.

PMID- 29194423
TI  - The Anti-Inflammatory Effect and Structure of EPCP1-2 from Crypthecodinium cohnii
      via Modulation of TLR4-NF-kappaB Pathways in LPS-Induced RAW 264.7 Cells.
AB  - Exopolysaccharide from Crypthecodinium cohnii (EPCP1-2) is a marine
      exopolysaccharide that evidences a variety of biological activities. We isolated
      a neutral polysaccharide from the fermentation liquid of Crypthecodinium cohnii
      (CP). In this study, a polysaccharide that is derived from Crypthecodinium cohnii
      were analyzed and its anti-inflammatory effect was evaluated on protein
      expression of toll-like receptor 4 and nuclear factor kappaB pathways in
      macrophages. The structural characteristics of EPCP1-2 were characterized by GC
      (gas chromatography) and GC-MS (gas Chromatography-Mass Spectrometer) analyses.
      The molecular weight was about 82.5 kDa. The main chain of EPCP1-2 consisted of
      (1->6)-linked mannopyranosyl, (1->6)-linked glucopyranosyl, branched-chain
      consisted of (1->3,6)-linked galactopyranosyl and terminal consisted of t-l
      Rhapyranosyl. The in vitro anti-inflammatory activity was representated through
      assay of proliferation rate, pro-inflammatory factor (NO) and expressions of
      proteins on RAW 264.7, the macrophage cell line. The results revealed that EPCP1
      2 exhibited significant anti-inflammatory activity by regulating the expression
      of toll-like receptor 4, mitogen-activated protein kinases, and Nuclear Factor
      kappaB protein.

PMID- 29194425
TI  - Contribution of Discretionary Foods and Drinks to Australian Children's Intake of
      Energy, Saturated Fat, Added Sugars and Salt.
AB  - Interventions are required to reduce children's consumption of discretionary
      foods and drinks. To intervene we need to identify appropriate discretionary
      choice targets. This study aimed to determine the main discretionary choice
      contributors to energy and key nutrient intakes in children aged 2-18 years.
      Secondary analyses were performed with population weighted, single 24 h dietary
      recall data from the 2011-2012 National Nutrition and Physical Activity Survey.
      Cakes, muffins, and slices; sweet biscuits; potato crisps and similar snacks;
      and, processed meats and sugar-sweetened drinks were relatively commonly consumed
      and were within the top three to five contributors to per capita energy,
      saturated fat, sodium, and/or added sugars. Per consumer intake identified cereal
      based takeaway foods; cakes, muffins and slices; meat pies and other savoury
      pastries; and, processed meats as top contributors to energy, saturated fat, and
      sodium across most age groups. Subgroups of sugar-sweetened drinks and cakes,
      muffins and slices were consistently key contributors to added sugars intake.
      This study identified optimal targets for interventions to reduce discretionary
      choices intake, likely to have the biggest impact on moderating energy intake
      while also reducing intakes of saturated fat, sodium and/or added sugars.

PMID- 29194424
TI  - Functional Foods and Lifestyle Approaches for Diabetes Prevention and Management.
AB  - Functional foods contain biologically active ingredients associated with
      physiological health benefits for preventing and managing chronic diseases, such
      as type 2 diabetes mellitus (T2DM). A regular consumption of functional foods may
      be associated with enhanced anti-oxidant, anti-inflammatory, insulin sensitivity,
      and anti-cholesterol functions, which are considered integral to prevent and
      manage T2DM. Components of the Mediterranean diet (MD)-such as fruits,
      vegetables, oily fish, olive oil, and tree nuts-serve as a model for functional
      foods based on their natural contents of nutraceuticals, including polyphenols,
      terpenoids, flavonoids, alkaloids, sterols, pigments, and unsaturated fatty
      acids. Polyphenols within MD and polyphenol-rich herbs-such as coffee, green tea,
      black tea, and yerba mate-have shown clinically-meaningful benefits on metabolic
      and microvascular activities, cholesterol and fasting glucose lowering, and anti
      inflammation and anti-oxidation in high-risk and T2DM patients. However,
      combining exercise with functional food consumption can trigger and augment
      several metabolic and cardiovascular protective benefits, but it is under
      investigated in people with T2DM and bariatric surgery patients. Detecting
      functional food benefits can now rely on an "omics" biological profiling of
      individuals' molecular, genetics, transcriptomics, proteomics, and metabolomics,
      but is under-investigated in multi-component interventions. A personalized
      approach for preventing and managing T2DM should consider biological and
      behavioral models, and embed nutrition education as part of lifestyle diabetes
      prevention studies. Functional foods may provide additional benefits in such an
      approach.

PMID- 29194426
TI  - Strategies to Achieve High-Performance White Organic Light-Emitting Diodes.
AB  - As one of the most promising technologies for next-generation lighting and
      displays, white organic light-emitting diodes (WOLEDs) have received enormous
      worldwide interest due to their outstanding properties, including high
      efficiency, bright luminance, wide viewing angle, fast switching, lower power
      consumption, ultralight and ultrathin characteristics, and flexibility. In this
      invited review, the main parameters which are used to characterize the
      performance of WOLEDs are introduced. Subsequently, the state-of-the-art
      strategies to achieve high-performance WOLEDs in recent years are summarized.
      Specifically, the manipulation of charges and excitons distribution in the four
      types of WOLEDs (fluorescent WOLEDs, phosphorescent WOLEDs, thermally activated
      delayed fluorescent WOLEDs, and fluorescent/phosphorescent hybrid WOLEDs) are
      comprehensively highlighted. Moreover, doping-free WOLEDs are described. Finally,
      issues and ways to further enhance the performance of WOLEDs are briefly
      clarified.

PMID- 29194428
TI  - Correction: Nabeshima, Y., et al. Analysis of Japanese Articles about Suicides
      Involving Charcoal Burning or Hydrogen Sulfide Gas. Int. J. Environ. Res. Public
      Health 2016, 13, 1013.
AB  - We wish to make the following three corrections to the published paper [...].

PMID- 29194429
TI  - Hazard Ranking Method for Populations Exposed to Arsenic in Private Water
      Supplies: Relation to Bedrock Geology.
AB  - Approximately one million people in the UK are served by private water supplies
      (PWS) where main municipal water supply system connection is not practical or
      where PWS is the preferred option. Chronic exposure to contaminants in PWS may
      have adverse effects on health. South West England is an area with elevated
      arsenic concentrations in groundwater and over 9000 domestic dwellings here are
      supplied by PWS. There remains uncertainty as to the extent of the population
      exposed to arsenic (As), and the factors predicting such exposure. We describe a
      hazard assessment model based on simplified geology with the potential to predict
      exposure to As in PWS. Households with a recorded PWS in Cornwall were recruited
      to take part in a water sampling programme from 2011 to 2013. Bedrock geologies
      were aggregated and classified into nine Simplified Bedrock Geological Categories
      (SBGC), plus a cross-cutting "mineralized" area. PWS were sampled by random
      selection within SBGCs and some 508 households volunteered for the study.
      Transformations of the data were explored to estimate the distribution of As
      concentrations for PWS by SBGC. Using the distribution per SBGC, we predict the
      proportion of dwellings that would be affected by high concentrations and rank
      the geologies according to hazard. Within most SBGCs, As concentrations were
      found to have log-normal distributions. Across these areas, the proportion of
      dwellings predicted to have drinking water over the prescribed concentration
      value (PCV) for As ranged from 0% to 20%. From these results, a pilot predictive
      model was developed calculating the proportion of PWS above the PCV for As and
      hazard ranking supports local decision making and prioritization. With further
      development and testing, this can help local authorities predict the number of
      dwellings that might fail the PCV for As, based on bedrock geology. The model
      presented here for Cornwall could be applied in areas with similar geologies.
      Application of the method requires independent validation and further groundwater
      derived PWS sampling on other geological formations.

PMID- 29194430
TI  - Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated
      Early Antiviral Response.
AB  - Cellular receptor-mediated signaling pathways play critical roles during the
      initial immune response to Human Cytomegalovirus (HCMV) infection. However, the
      involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular
      matrix metalloproteinase inducer) in the antiviral response to HCMV infection is
      still unknown. Here, we demonstrated the specific knockdown of CD147
      significantly decreased HCMV-induced activation of NF-kappaB and Interferon-beta
      (IFN-beta), which contribute to the cellular antiviral responses. Next, we
      confirmed that HCMV-encoded miR-US25-1-5p could target the 3' UTR (Untranslated
      Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low
      multiplicity of infection (MOI). The expression and secretion of Cyclophilin A
      (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated
      in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV
      triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated
      protein kinases)/NF-kappaB axis signaling pathway. These findings reveal an
      important HCMV mechanism for evading antiviral innate immunity through its
      encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential
      cause of HCMV inflammatory disorders due to the secretion of proinflammatory
      cytokine CyPA.

PMID- 29194431
TI  - Characteristics of Plantar Loads During Walking in Patients with Knee
      Osteoarthritis.
AB  - BACKGROUND Knee osteoarthritis (KOA) is a common disease that can change the load
      on lower limbs during walking. Plantar loads in patients with KOA may provide a
      basis for clinical decisions regarding footwear and foot orthoses. This study
      aimed to compare plantar loads in females with and without KOA during gait.
      MATERIAL AND METHODS Plantar pressure during walking was recorded in 23 females
      with KOA and 23 females without KOA. Maximum force (MF), contact area (CA), and
      peak pressure (PP) were measured at 7 different regions underneath the foot,
      named heel (M1), midfoot (M2), first metatarsophalangeal joint (MPJ) (M3), second
      MPJ (M4), third to fifth MPJ (M5), hallux (M6), and lesser toes (M7). RESULTS PPs
      for M2 and (M3) in females with KOA were higher than those in females without
      KOA. High PPs were also found in females with KOA for M2, M3, and M4. CONCLUSIONS
      Increased plantar loading in females with KOA may lead to foot pronation and gait
      changes during walking. Plantar loading may be offered to patients with KOA when
      considering footwear and foot orthoses.

PMID- 29194427
TI  - Control of Endogenous Auxin Levels in Plant Root Development.
AB  - In this review, we summarize the different biosynthesis-related pathways that
      contribute to the regulation of endogenous auxin in plants. We demonstrate that
      all known genes involved in auxin biosynthesis also have a role in root
      formation, from the initiation of a root meristem during embryogenesis to the
      generation of a functional root system with a primary root, secondary lateral
      root branches and adventitious roots. Furthermore, the versatile adaptation of
      root development in response to environmental challenges is mediated by both
      local and distant control of auxin biosynthesis. In conclusion, auxin homeostasis
      mediated by spatial and temporal regulation of auxin biosynthesis plays a central
      role in determining root architecture.

PMID- 29194432
TI  - Do cannabinoids constitute a therapeutic alternative for anorexia nervosa?
AB  - INTRODUCTION: Cannabinoids have been postulated as an alternative for anorexia
      nervosa. However, their actual clinical efficacy and safety are still discussed.
      METHODS: To answer this question we used Epistemonikos, the largest database of
      systematic reviews in health, which is maintained by screening multiple
      information sources, including MEDLINE, EMBASE, Cochrane, among others. We
      extracted data from the systematic reviews, reanalyzed data of primary studies
      and generated a summary of findings table using the GRADE approach. RESULTS AND
      CONCLUSIONS: We identified four systematic reviews including two primary studies,
      both corresponding to randomized trials. We concluded cannabinoids might not
      increase weight or improve symptoms in anorexia nervosa, and are probably
      associated to frequent adverse effects.

PMID- 29194433
TI  - Health inequalities and the impact on the prevalence of cardiovascular risk
      factors and chronic complications in Argentina: a study on national risk factors
      surveys.
AB  - BACKGROUND: In Argentina, there is evidence of health inequalities, measured both
      at the general level and also using income as a parameter of social status.
      However, few studies address the issue of health equality in chronic diseases
      such as cardiovascular risk factors. OBJECTIVE: To describe health inequalities,
      using cardiovascular risk factors as a tracer for chronic diseases in different
      areas of the country and over time. In addition, we aim to identify differences
      in the quality of care provided to people with cardiovascular risk factors,
      between 2005 and 2009. METHODS: This is an observational study, which used
      descriptive and quantitative methods. Data from the National Risk Factors Survey
      from 2005 and 2009 in the cohorts who have chronic diseases (hypertension,
      diabetes, dyslipidemia and overweight/obesity) were analyzed to assess
      associations between health status and several demographic, epidemiological and
      socioeconomic variables. Additionally, clinical and metabolic characteristics of
      people with diabetes and other cardiovascular risks factors were analyzed in 2005
      and 2009 using the database Quality of Diabetes Care (QUALIDIAB). RESULTS:
      Cardiovascular risk factors are more frequent in people with lower socioeconomic
      status, regardless of the indicator. The inequalities detected showed the worst
      indicators in strata with lower education and income, with the same results both
      nationwide and separated by region. This inequalities were more pronounced in
      2009, and their magnitude changed by region and cardiovascular risk factor. From
      2005 to 2009, body mass index, blood glucose and HbA1c value increased. In
      contrast, both systolic blood pressure and triglycerides decreased, with no
      significant changes in total cholesterol and diastolic blood pressure.
      CONCLUSION: Cardiovascular risk factors present inequalities attributed to social
      status manifesting at both national and regional levels.

PMID- 29194434
TI  - Metabomatching: Using genetic association to identify metabolites in proton NMR
      spectroscopy.
AB  - A metabolome-wide genome-wide association study (mGWAS) aims to discover the
      effects of genetic variants on metabolome phenotypes. Most mGWASes use as
      phenotypes concentrations of limited sets of metabolites that can be identified
      and quantified from spectral information. In contrast, in an untargeted mGWAS
      both identification and quantification are forgone and, instead, all measured
      metabolome features are tested for association with genetic variants. While the
      untargeted approach does not discard data that may have eluded identification,
      the interpretation of associated features remains a challenge. To address this
      issue, we developed metabomatching to identify the metabolites underlying
      significant associations observed in untargeted mGWASes on proton NMR metabolome
      data. Metabomatching capitalizes on genetic spiking, the concept that because
      metabolome features associated with a genetic variant tend to correspond to the
      peaks of the NMR spectrum of the underlying metabolite, genetic association can
      allow for identification. Applied to the untargeted mGWASes in the SHIP and
      CoLaus cohorts and using 180 reference NMR spectra of the urine metabolome
      database, metabomatching successfully identified the underlying metabolite in 14
      of 19, and 8 of 9 associations, respectively. The accuracy and efficiency of our
      method make it a strong contender for facilitating or complementing metabolomics
      analyses in large cohorts, where the availability of genetic, or other data,
      enables our approach, but targeted quantification is limited.

PMID- 29194435
TI  - Adiposity QTL Adip20 decomposes into at least four loci when dissected using
      congenic strains.
AB  - An average mouse in midlife weighs between 25 and 30 g, with about a gram of
      tissue in the largest adipose depot (gonadal), and the weight of this depot
      differs between inbred strains. Specifically, C57BL/6ByJ mice have heavier
      gonadal depots on average than do 129P3/J mice. To understand the genetic
      contributions to this trait, we mapped several quantitative trait loci (QTLs) for
      gonadal depot weight in an F2 intercross population. Our goal here was to fine
      map one of these QTLs, Adip20 (formerly Adip5), on mouse chromosome 9. To that
      end, we analyzed the weight of the gonadal adipose depot from newly created
      congenic strains. Results from the sequential comparison method indicated at
      least four rather than one QTL; two of the QTLs were less than 0.5 Mb apart, with
      opposing directions of allelic effect. Different types of evidence (missense and
      regulatory genetic variation, human adiposity/body mass index orthologues, and
      differential gene expression) implicated numerous candidate genes from the four
      QTL regions. These results highlight the value of mouse congenic strains and the
      value of this sequential method to dissect challenging genetic architecture.

PMID- 29194436
TI  - Characterisation of the pathogenic effects of the in vivo expression of an ALS
      linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor
      neurons.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular
      disorder characterised by selective loss of motor neurons leading to fatal
      paralysis. Current therapeutic approaches are limited in their effectiveness.
      Substantial advances in understanding ALS disease mechanisms has come from the
      identification of pathogenic mutations in dominantly inherited familial ALS
      (FALS). We previously reported a coding mutation in D-amino acid oxidase
      (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co
      agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using
      primary motor neuron cultures or motor neuron cell lines we demonstrated that
      expression of DAOR199W, promoted the formation of ubiquitinated protein
      aggregates, activated autophagy and increased apoptosis. The aim of this study
      was to characterise the effects of DAOR199W in vivo, using transgenic mice
      overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were
      evident in mice expressing DAOR199W, which were associated with a significant
      loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When
      separated by gender, this effect was greater in females (26%; p< 0.0132). In
      addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse
      model of ALS to determine whether the effects of SOD1G93A were potentiated in the
      double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not
      affected, onset of neurological signs was significantly earlier in female double
      transgenic animals than their female SOD1G93A littermates (125 days vs 131 days,
      P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor
      neuron function (i.e. kyphosis and loss of motor neurons) were detected which
      were most marked in females and could contribute to the earlier onset of
      neurological signs in double transgenic females compared to SOD1G93A littermates,
      highlighting the importance of recognizing gender effects present in animal
      models of ALS.

PMID- 29194437
TI  - An introduction to the 'Psycho-Physiological-Stress-Test' (PPST)-A standardized
      instrument for evaluating stress reactions.
AB  - Using a standardized instrument to evaluate patients' stress reactions has become
      more important in daily clinical routines. Different signs or symptoms of stress
      are often unilaterally explored: the physiological, psychological or social
      aspects of stress disorders are each viewed on a single dimension. However, all
      dimensions afflict patients who have persistent health problems due to chronic
      stress. Therefore, it is important to use a multidimensional approach to acquire
      data. The 'Psycho-Physiological-Stress-Test' (PPST) was established to achieve a
      comprehensive understanding of stress and was further developed at the Charite
      Universitatsmedizin Berlin in collaboration with the Psychological Department of
      Freie Universitat Berlin. The PPST includes a series of varying stress phases,
      embedded in two periods of rest. Physiological and psychological parameters are
      simultaneously measured throughout the test session. Specifically, the PPST
      activates the sympathetic stress axis, which is measured by heart rate, blood
      pressure, respiration depth and rate, electro dermal activation and muscle
      tension (frontalis, masseter, trapezius). Psychological data are simultaneously
      collected, and include performance, motivation, emotion and behavior. After
      conducting this diagnostic test, it is possible to identify individual stress
      patterns that can be discussed with the individual patient to develop and
      recommend (outpatient) treatment strategies. This paper introduces the PPST as a
      standardized way to evaluate stress reactions by presenting the results from a
      sample of psychosomatic inpatients (n = 139) who were treated in Charite
      Universitatsmedizin Berlin, Germany. We observed that the varying testing
      conditions provoked adjusted changes in the different physiological parameters
      and psychological levels.

PMID- 29194438
TI  - A temporal comparison of sex-aggregation pheromone gland content and dynamics of
      release in three members of the Lutzomyia longipalpis (Diptera: Psychodidae)
      species complex.
AB  - BACKGROUND: Lutzomyia longipalpis is the South American vector of Leishmania
      infantum, the etiologic agent of visceral leishmaniasis (VL). Male L. longipalpis
      produce a sex-aggregation pheromone that is critical in mating, yet very little
      is known about its accumulation over time or factors involved in release. This
      laboratory study aimed to compare accumulation of pheromone over time and
      determine factors that might influence release in three members of the L.
      longipalpis species complex. METHODOLOGY/PRINCIPAL FINDINGS: We investigated male
      sex-aggregation pheromone gland content at different ages and the release rate of
      pheromone in the presence or absence of females under different light conditions
      by gas chromatography-mass spectrometry (GC-MS). Pheromone gland content was
      determined by extraction of whole males and pheromone release rate was determined
      by collection of headspace volatiles. Pheromone gland content appeared age
      related and pheromone began to accumulate between 6 to 12 h post eclosion and
      gradually increased until males were 7-9 days old. The greatest amount was
      detected in 9-day old Campo Grande males ((S)-9-methylgermacrene-B; X +/- SE:
      203.5 +/- 57.4 ng/male) followed by Sobral 2S males (diterpene; 199.9 +/- 34.3)
      and Jacobina males ((1S,3S,7R)-3-methyl-alpha-himachalene; 128.8 +/- 30.3) at 7
      days old. Pheromone release was not continuous over time. During a 4-hour period,
      the greatest quantities of pheromone were released during the first hour, when
      wing beating activity was most intense. It was then substantially diminished for
      the remainder of the time. During a 24 h period, 4-5 day old male sand flies
      released approximately 63 +/- 11% of the pheromone content of their glands,
      depending on the chemotype. The presence of females significantly increased
      pheromone release rate. The light regime under which the sand flies were held had
      little influence on pheromone release except on Sobral 2S chemotype.
      CONCLUSIONS/SIGNIFICANCE: Accumulation of pheromone appears to occur at different
      rates in the different chemotypes examined and results in differing amounts being
      present in glands over time. Release of accumulated pheromone is not passive, but
      depends on biotic (presence of females) and abiotic (light) circumstances. There
      are marked differences in content and release between the members of the complex
      suggesting important behavioural, biosynthetic and ecological differences between
      them.

PMID- 29194439
TI  - Genetic drift and selection in many-allele range expansions.
AB  - We experimentally and numerically investigate the evolutionary dynamics of four
      competing strains of E. coli with differing expansion velocities in radially
      expanding colonies. We compare experimental measurements of the average fraction,
      correlation functions between strains, and the relative rates of genetic domain
      wall annihilations and coalescences to simulations modeling the population as a
      one-dimensional ring of annihilating and coalescing random walkers with
      deterministic biases due to selection. The simulations reveal that the
      evolutionary dynamics can be collapsed onto master curves governed by three
      essential parameters: (1) an expansion length beyond which selection dominates
      over genetic drift; (2) a characteristic angular correlation describing the size
      of genetic domains; and (3) a dimensionless constant quantifying the interplay
      between a colony's curvature at the frontier and its selection length scale. We
      measure these parameters with a new technique that precisely measures small
      selective differences between spatially competing strains and show that our
      simulations accurately predict the dynamics without additional fitting. Our
      results suggest that the random walk model can act as a useful predictive tool
      for describing the evolutionary dynamics of range expansions composed of an
      arbitrary number of genotypes with different fitnesses.

PMID- 29194440
TI  - Attacking the mosquito on multiple fronts: Insights from the Vector Control
      Optimization Model (VCOM) for malaria elimination.
AB  - BACKGROUND: Despite great achievements by insecticide-treated nets (ITNs) and
      indoor residual spraying (IRS) in reducing malaria transmission, it is unlikely
      these tools will be sufficient to eliminate malaria transmission on their own in
      many settings today. Fortunately, field experiments indicate that there are many
      promising vector control interventions that can be used to complement ITNs and/or
      IRS by targeting a wide range of biological and environmental mosquito resources.
      The majority of these experiments were performed to test a single vector control
      intervention in isolation; however, there is growing evidence and consensus that
      effective vector control with the goal of malaria elimination will require a
      combination of interventions. METHOD AND FINDINGS: We have developed a model of
      mosquito population dynamic to describe the mosquito life and feeding cycles and
      to optimize the impact of vector control intervention combinations at suppressing
      mosquito populations. The model simulations were performed for the main three
      malaria vectors in sub-Saharan Africa, Anopheles gambiae s.s, An. arabiensis and
      An. funestus. We considered areas having low, moderate and high malaria
      transmission, corresponding to entomological inoculation rates of 10, 50 and 100
      infective bites per person per year, respectively. In all settings, we considered
      baseline ITN coverage of 50% or 80% in addition to a range of other vector
      control tools to interrupt malaria transmission. The model was used to sweep
      through parameters space to select the best optimal intervention packages. Sample
      model simulations indicate that, starting with ITNs at a coverage of 50% (An.
      gambiae s.s. and An. funestus) or 80% (An. arabiensis) and adding interventions
      that do not require human participation (e.g. larviciding at 80% coverage,
      endectocide treated cattle at 50% coverage and attractive toxic sugar baits at
      50% coverage) may be sufficient to suppress all the three species to an extent
      required to achieve local malaria elimination. CONCLUSION: The Vector Control
      Optimization Model (VCOM) is a computational tool to predict the impact of
      combined vector control interventions at the mosquito population level in a range
      of eco-epidemiological settings. The model predicts specific combinations of
      vector control tools to achieve local malaria elimination in a range of eco
      epidemiological settings and can assist researchers and program decision-makers
      on the design of experimental or operational research to test vector control
      interventions. A corresponding graphical user interface is available for national
      malaria control programs and other end users.

PMID- 29194441
TI  - Candida albicans FRE8 encodes a member of the NADPH oxidase family that produces
      a burst of ROS during fungal morphogenesis.
AB  - Until recently, NADPH oxidase (NOX) enzymes were thought to be a property of
      multicellularity, where the reactive oxygen species (ROS) produced by NOX acts in
      signaling processes or in attacking invading microbes through oxidative damage.
      We demonstrate here that the unicellular yeast and opportunistic fungal pathogen
      Candida albicans is capable of a ROS burst using a member of the NOX enzyme
      family, which we identify as Fre8. C. albicans can exist in either a unicellular
      yeast-like budding form or as filamentous multicellular hyphae or pseudohyphae,
      and the ROS burst of Fre8 begins as cells transition to the hyphal state. Fre8 is
      induced during hyphal morphogenesis and specifically produces ROS at the growing
      tip of the polarized cell. The superoxide dismutase Sod5 is co-induced with Fre8
      and our findings are consistent with a model in which extracellular Sod5 acts as
      partner for Fre8, converting Fre8-derived superoxide to the diffusible H2O2
      molecule. Mutants of fre8Delta/Delta exhibit a morphogenesis defect in vitro and
      are specifically impaired in development or maintenance of elongated hyphae, a
      defect that is rescued by exogenous sources of H2O2. A fre8Delta/Delta deficiency
      in hyphal development was similarly observed in vivo during C. albicans invasion
      of the kidney in a mouse model for disseminated candidiasis. Moreover C. albicans
      fre8Delta/Delta mutants showed defects in a rat catheter model for biofilms.
      Together these studies demonstrate that like multicellular organisms, C. albicans
      expresses NOX to produce ROS and this ROS helps drive fungal morphogenesis in the
      animal host.

PMID- 29194442
TI  - Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes
      revealed by molecular simulations.
AB  - While nucleosome positioning on eukaryotic genome play important roles for
      genetic regulation, molecular mechanisms of nucleosome positioning and sliding
      along DNA are not well understood. Here we investigated thermally-activated
      spontaneous nucleosome sliding mechanisms developing and applying a coarse
      grained molecular simulation method that incorporates both long-range
      electrostatic and short-range hydrogen-bond interactions between histone octamer
      and DNA. The simulations revealed two distinct sliding modes depending on the
      nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one
      base pair step in a rotation-coupled manner, akin to screw-like motions. On the
      contrary, a strong positioning sequence, the so-called 601 sequence, exhibits
      rare, abrupt transitions of five and ten base pair steps without rotation.
      Moreover, we evaluated the importance of hydrogen bond interactions on the
      sliding mode, finding that strong and weak bonds favor respectively the rotation
      coupled and -uncoupled sliding movements.

PMID- 29194443
TI  - Considering the ethics of big data research: A case of Twitter and ISIS/ISIL.
AB  - This is a formal commentary, responding to Matthew Curran Benigni, Kenneth
      Joseph, and Kathleen Carley's contribution, "Online extremism and the communities
      that sustain it: Detecting the ISIS supporting community on Twitter". This brief
      review reflects on the ethics of big data research methodologies, and how novel
      methods complicate long-standing principles of research ethics. Specifically, the
      concept of the "data subject" as a corollary, or replacement, of "human subject"
      is considered.

PMID- 29194444
TI  - Behavioral stress alters corticolimbic microglia in a sex- and brain region
      specific manner.
AB  - Women are more susceptible to numerous stress-linked psychological disorders
      (e.g., depression) characterized by dysfunction of corticolimbic brain regions
      critical for emotion regulation and cognitive function. Although sparsely
      investigated, a number of studies indicate sex differences in stress effects on
      neuronal structure, function, and behaviors associated with these regions. We
      recently demonstrated a basal sex difference in- and differential effects of
      stress on- microglial activation in medial prefrontal cortex (mPFC). The resident
      immune cells of the brain, microglia are implicated in synaptic and dendritic
      plasticity, and cognitive-behavioral function. Here, we examined the effects of
      acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on
      microglial density and morphology, as well as immune factor expression in
      orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus
      (DHC) in male and female rats. Microglia were visualized, classified based on
      their morphology, and stereologically counted. Microglia-associated transcripts
      (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain
      punches from each region. Expression of genes linked with cellular stress,
      neuroimmune state, and neuron-microglia communication varied between unstressed
      male and female rats in a region-specific manner. In OFC, chronic stress
      upregulated a wider variety of immune factors in females than in males. Acute
      stress increased microglia-associated transcripts in BLA in males, whereas
      chronic stress altered immune factor expression in BLA more broadly in females.
      In DHC, chronic stress increased immune factor expression in males but not
      females. Moreover, acute and chronic stress differentially affected microglial
      morphological activation state in male and female rats across all brain regions
      investigated. In males, chronic stress altered microglial activation in a pattern
      consistent with microglial involvement in stress-induced dendritic remodeling
      across OFC, BLA, and DHC. Together, these data suggest the potential for
      microglia-mediated sex differences in stress effects on neural structure,
      function, and behavior.

PMID- 29194446
TI  - Online extremism and the communities that sustain it: Detecting the ISIS
      supporting community on Twitter.
AB  - The Islamic State of Iraq and ash-Sham (ISIS) continues to use social media as an
      essential element of its campaign to motivate support. On Twitter, ISIS' unique
      ability to leverage unaffiliated sympathizers that simply retweet propaganda has
      been identified as a primary mechanism in their success in motivating both
      recruitment and "lone wolf" attacks. The present work explores a large community
      of Twitter users whose activity supports ISIS propaganda diffusion in varying
      degrees. Within this ISIS supporting community, we observe a diverse range of
      actor types, including fighters, propagandists, recruiters, religious scholars,
      and unaffiliated sympathizers. The interaction between these users offers unique
      insight into the people and narratives critical to ISIS' sustainment. In their
      entirety, we refer to this diverse set of users as an online extremist community
      or OEC. We present Iterative Vertex Clustering and Classification (IVCC), a
      scalable analytic approach for OEC detection in annotated heterogeneous networks,
      and provide an illustrative case study of an online community of over 22,000
      Twitter users whose online behavior directly advocates support for ISIS or
      contibutes to the group's propaganda dissemination through retweets.

PMID- 29194445
TI  - Safety and efficacy of an oxycodone vaccine: Addressing some of the unique
      considerations posed by opioid abuse.
AB  - Among vaccines aimed at treating substance use disorders, those targeting opioids
      present several unique medication development challenges. 1) Opioid overdose is a
      common complication of abuse, so it is desirable for an opioid vaccine to block
      the toxic as well as the addictive effects of opioids. 2) It is important that an
      opioid vaccine not interfere with the action of opioid antagonists used to
      reverse opioid overdose or treat addiction. 3) Some opioids are immunosuppressive
      and chronic ongoing opioid use could interfere with vaccine immunogenicity. 4)
      Although antibody-bound oxycodone is unable to enter the brain because of its
      size, it might still be able to activate peripheral opioid receptors. To assess
      vaccine impact on opioid toxicity, rats vaccinated with oxycodone conjugated to
      keyhole limpet hemocyanin subunit dimer (OXY-dKLH) adsorbed to alum or controls
      vaccinated with dKLH were compared with regard to oxycodone-induced hotplate
      analgesia and oxycodone-induced respiratory depression and bradycardia.
      Vaccination shifted the dose-response curves to the right, representing
      protection, for each of these endpoints. Naloxone was equally effective in both
      OXY-dKLH and control groups, providing complete and rapid reversal of respiratory
      depression. The administration of a long-acting naltrexone formulation during
      vaccination did not impair vaccine immunogenicity in mice. Similarly, serum anti
      oxycodone antibody titers were not altered by continuous morphine infusion during
      vaccination compared to opioid-naive controls. Competitive ELISA assay showed
      negligible or low affinity of immune antiserum for endogenous opioids or opioid
      antagonists. In vitro receptor binding assays showed that antibody-bound
      oxycodone does not activate mu opioid receptors. These data support further study
      of OXY-dKLH as a potential treatment for oxycodone abuse and suggest that
      vaccination might also reduce the severity of oxycodone overdose.

PMID- 29194447
TI  - Sevoflurane causes greater QTc interval prolongation in chronically hyperglycemic
      patients than in normoglycemic patients.
AB  - QTc interval prolongation is a serious diabetic complication and increases
      mortality rate. Hyperglycemia inhibits the rapid component of delayed rectifier
      potassium channel currents (Ikr) and prolongs the QTc interval on
      electrocardiograms. Sevoflurane also inhibits the Ikr and causes QTc interval
      prolongation. In fact, torsade de pointes occurred in a patient with poorly
      controlled diabetes mellitus during sevoflurane anesthesia. We enrolled 74
      patients, including 37 normoglycemic patients (glycated hemoglobin [HbA1c]:
      <6.5%) (NG group) and 37 chronically hyperglycemic patients (HbA1c: >=6.5%) (HG
      group). Anesthesia was induced with 2 mg/kg propofol and 0.3 MUg/kg/min
      remifentanil, and maintained with 2% sevoflurane in 40% O2 and 0.2-0.3 MUg/kg/min
      remifentanil. The QT interval and Tp-e interval (from the peak to the end of the
      T wave) were measured before and at 5, 10, 30, 60, 90, and 120 min after the
      administration of sevoflurane and adjusted for the patient's heart rate (QTc and
      Tp-ec, respectively). P-values of <0.05 were considered statistically
      significant. The QTc and the Tp-ec intervals of the two groups did not differ
      significantly before the administration of sevoflurane. The QTc interval
      gradually increased with time in both groups and was significantly longer than
      the baseline value at 10 min after the administration of sevoflurane in both
      groups. The QTc interval of the HG group was significantly longer than that of
      the NG group at 90 min and 120 min after the administration of sevoflurane. The
      Tp-ec interval was not affected by sevoflurane in either group.We have
      demonstrated that sevoflurane significantly prolongs the QTc interval, and that
      the extent of the prolongation is significantly greater in chronically
      hyperglycemic patients than in normoglycemic patients. Although Tp-ec is not
      affected by sevoflurane, it should be noted that the simultaneous blockade of
      potassium channels would increase the risk of arrhythmias.

PMID- 29194448
TI  - Interleukin-1beta (IL-1beta)-induced Notch ligand Jagged1 suppresses mitogenic
      action of IL-1beta on human dystrophic myogenic cells.
AB  - Duchenne muscular dystrophy (DMD) is a severe X-linked recessive muscle disorder
      caused by mutations in the dystrophin gene. Nonetheless, secondary processes
      involving perturbation of muscle regeneration probably exacerbate disease
      progression, resulting in the fatal loss of muscle in DMD patients. A dysfunction
      of undifferentiated myogenic cells is the most likely cause for the reduction of
      regenerative capacity of muscle. To clarify molecular mechanisms in perturbation
      of the regenerative capacity of DMD muscle, we have established several NCAM
      (CD56)-positive immortalized human dystrophic and non-dystrophic myogenic cell
      lines from DMD and healthy muscles. A pro-inflammatory cytokine, IL-1beta,
      promoted cell cycle progression of non-dystrophic myogenic cells but not DMD
      myogenic cells. In contrast, IL-1beta upregulated the Notch ligand Jagged1 gene
      in DMD myogenic cells but not in non-dystrophic myogenic cells. Knockdown of
      Jagged1 in DMD myogenic cells restored the IL-1beta-promoted cell cycle
      progression. Conversely, enforced expression of Jagged1-blocked IL-1beta promoted
      proliferation of non-dystrophic myogenic cells. In addition, IL-1beta prevented
      myogenic differentiation of DMD myogenic cells depending on Jagged1 but not of
      non-dystrophic myogenic cells. These results demonstrate that Jagged1 induced by
      IL-1beta in DMD myogenic cells modified the action of IL-1beta and reduced the
      ability to proliferate and differentiate. IL-1beta induced Jagged1 gene
      expression may be a feedback response to excess stimulation with this cytokine
      because high IL-1beta (200-1000 pg/ml) induced Jagged1 gene expression even in
      non-dystrophic myogenic cells. DMD myogenic cells are likely to acquire the
      susceptibility of the Jagged1 gene to IL-1beta under the microcircumstances in
      DMD muscles. The present results suggest that Jagged1 induced by IL-1beta plays a
      crucial role in the loss of muscle regeneration capacity of DMD muscles. The IL
      1beta/Jagged1 pathway may be a new therapeutic target to ameliorate exacerbation
      of muscular dystrophy in a dystrophin-independent manner.

PMID- 29194450
TI  - Risk of infertility following pelvic angiographic embolization in female patients
      with pelvic fractures: A nationwide population-based cohort study in Taiwan.
AB  - Pelvic angiographic embolization is an effective procedure to provide haemostasis
      in patients with pelvic fractures. However, management with repeated follow-up
      radiographs may result in infertility. The study aimed to evaluate the risk of
      infertility following pelvic fracture treated with pelvic angiographic
      embolization in female patients. We used data from the National Health Insurance
      Research Database (NHIRD) provided by the Bureau of National Health Insurance of
      the Department of Health in Taiwan from the period of 1997-2010. A total of 36
      and 18,029 patients were included in the case and control cohorts, respectively.
      The risk estimations for the case and control cohorts were compared using a Cox's
      proportional hazards regression model. The significance level was set at <0.05.
      After adjusting for possible confounding factors, the incidence of infertility in
      the case cohort was nearly 30.7-fold higher than that in the control cohort
      (adjust hazard ratio [HR] = 30.7, 95% confidence interval [CI] = 10.643-70.109).
      Patients between 15-35 years of age had a much higher incidence of infertility in
      the case cohort than in the control cohort (adjusted HR = 49.9, 95% CI = 15.177
      64.099). Taken together, pelvic fractures in female patients treated with
      arterioembolization for haemostasis might be associated with a higher risk of
      infertility in Taiwan. Physicians should be aware of the link and inform patients
      of this risk prior to arterioembolization.

PMID- 29194449
TI  - Reported selection criteria for adult acquired flatfoot deformity and posterior
      tibial tendon dysfunction: Are they one and the same? A systematic review.
AB  - BACKGROUND: Posterior tibial tendon dysfunction (PTTD) and adult acquired
      flatfoot deformity (AAFD) are used interchangeably, although both suggest quite
      different pathological processes. OBJECTIVE: To investigate key differences in
      selection criteria used for inclusion into research studies. METHODS: An
      electronic database search was performed from inception to June 2016. All primary
      research articles with clear inclusion/diagnostic criteria for PTTD or AAFD were
      included in the review. All criteria were extracted and synthesised into one
      aggregate list. Frequencies of recurring criteria were calculated and reported
      for each stage of the conditions. RESULTS: Of the potentially eligible papers,
      148 (65%) did not specify inclusion/selection criteria for PTTD or AAFD and were
      excluded. Eligibility criteria were reported 82 times in the 80 included papers,
      with 69 descriptions for PTTD and 13 for AAFD. After synthesis of criteria from
      all papers, there were 18 key signs and symptoms. Signs and symptoms were
      considered to be those relating to tendon pathology and those relating to
      structural deformity. The total number of individual inclusion/diagnostic
      criteria ranged from 2 to 9. The majority of articles required signs of both
      tendon dysfunction and structural deformity (84% for AAFD and 81% for PTTD).
      Across both groups, the most frequently reported criteria were abduction of the
      forefoot (11.5% of total criteria used), the presence of a flexible deformity
      (10.2%) and difficulty performing a single leg heel raise (10.0%). This was
      largely the case for the PTTD articles, whereas the AAFD articles were more
      focused on postural issues such as forefoot abduction, medial arch collapse, and
      hindfoot valgus (each 16.7%). CONCLUSION: As well as synthesising the available
      literature and providing reporting recommendations, this review has identified
      that many papers investigating PTTD/AAFD do not state condition-specific
      selection criteria and that this limits their clinical applicability. Key signs
      and symptoms of PTTD and AAFD appear similar, except in early PTTD where no
      structural deformity is present. We recommend that PTTD is the preferred
      terminology for the condition associated with signs of local tendon dysfunction
      with pain and/or swelling along the tendon and difficulty with inversion and/or
      single leg heel raise characterising stage I and difficulty with single leg heel
      raise and a flexible flatfoot deformity characterizing stage II PTTD. While AAFD
      may be useful as an umbrella term for acquired flatfoot deformities, the specific
      associated aetiology should be reported in studies to aid consolidation and
      implementation of research into practice. TRIAL REGISTRATION: Prospero ID:
      42016046943.

PMID- 29194451
TI  - Adiponectin receptor 1 resists the decline of serum osteocalcin and GPRC6A
      expression in ovariectomized mice.
AB  - Hormonal changes that cause metabolic complications are a common problem in
      postmenopausal women. Adiponectin and osteocalcin are cytokines associated with
      glucose regulatory and insulin sensitized function in postmenopausal stages. The
      current study investigated the role of adiponectin signaling and osteocalcin
      mediated function in glucose metabolism in ovariectomized mice. In a mouse
      menopausal-related metabolic disorder model, overexpression of adiponectin
      receptor 1 improved glucose tolerance and caused resistance to body weight
      increase and decline of serum osteocalcin. Furthermore, adiponectin receptor 1
      transgenic ovariectomized mice had higher GPRC6A (the putative osteocalcin
      receptor) expression in muscle tissue. Immunofluorescence indicated that GPRC6A
      and adiponectin receptor 1 were co-localized in mouse muscle tissues. The present
      finding suggested adiponectin receptor 1 can mediate the improvement of glucose
      metabolism by osteocalcin in ovariectomized mice. Our findings imply the
      possibility to ameliorate menopause-induced metabolic disorder by GPRC6A and
      adiponectin signaling.

PMID- 29194453
TI  - Neural correlates of processing sentences and compound words in Chinese.
AB  - Sentence reading involves multiple linguistic operations including processing of
      lexical and compositional semantics, and determining structural and grammatical
      relationships among words. Previous studies on Indo-European languages have
      associated left anterior temporal lobe (aTL) and left interior frontal gyrus
      (IFG) with reading sentences compared to reading unstructured word lists. To
      examine whether these brain regions are also involved in reading a typologically
      distinct language with limited morphosyntax and lack of agreement between
      sentential arguments, an FMRI study was conducted to compare passive reading of
      Chinese sentences, unstructured word lists and disconnected character lists that
      are created by only changing the order of an identical set of characters. Similar
      to previous findings from other languages, stronger activation was found in
      mainly left-lateralized anterior temporal regions (including aTL) for reading
      sentences compared to unstructured word and character lists. On the other hand,
      stronger activation was identified in left posterior temporal sulcus for reading
      unstructured words compared to unstructured characters. Furthermore, reading
      unstructured word lists compared to sentences evoked stronger activation in left
      IFG and left inferior parietal lobule. Consistent with the literature on Indo
      European languages, the present results suggest that left anterior temporal
      regions subserve sentence-level integration, while left IFG supports restoration
      of sentence structure. In addition, left posterior temporal sulcus is associated
      with morphological compounding. Taken together, reading Chinese sentences engages
      a common network as reading other languages, with particular reliance on
      integration of semantic constituents.

PMID- 29194452
TI  - Hyperthyroidism, but not hypertension, impairs PITX2 expression leading to Wnt
      microRNA-ion channel remodeling.
AB  - PITX2 is a homeobox transcription factor involved in embryonic left/right
      signaling and more recently has been associated to cardiac arrhythmias. Genome
      wide association studies have pinpointed PITX2 as a major player underlying
      atrial fibrillation (AF). We have previously described that PITX2 expression is
      impaired in AF patients. Furthermore, distinct studies demonstrate that Pitx2
      insufficiency leads to complex gene regulatory network remodeling, i.e.
      Wnt>microRNAs, leading to ion channel impairment and thus to arrhythmogenic
      events in mice. Whereas large body of evidences has been provided in recent years
      on PITX2 downstream signaling pathways, scarce information is available on
      upstream pathways influencing PITX2 in the context of AF. Multiple risk factors
      are associated to the onset of AF, such as e.g. hypertension (HTN),
      hyperthyroidism (HTD) and redox homeostasis impairment. In this study we have
      analyzed whether HTN, HTD and/or redox homeostasis impact on PITX2 and its
      downstream signaling pathways. Using rat models for spontaneous HTN (SHR) and
      experimentally-induced HTD we have observed that both cardiovascular risk factors
      lead to severe Pitx2 downregulation. Interesting HTD, but not SHR, leads to up
      regulation of Wnt signaling as well as deregulation of multiple microRNAs and ion
      channels as previously described in Pitx2 insufficiency models. In addition,
      redox signaling is impaired in HTD but not SHR, in line with similar findings in
      atrial-specific Pitx2 deficient mice. In vitro cell culture analyses using gain-
      and loss-of-function strategies demonstrate that Pitx2, Zfhx3 and Wnt signaling
      influence redox homeostasis in cardiomyocytes. Thus, redox homeostasis seems to
      play a pivotal role in this setting, providing a regulatory feedback loop.
      Overall these data demonstrate that HTD, but not HTN, can impair Pitx2>>Wnt
      pathway providing thus a molecular link to AF.

PMID- 29194455
TI  - Correction: Dynamics and impact of homologous recombination on the evolution of
      Legionella pneumophila.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1006855.].

PMID- 29194456
TI  - Tools for retargeting proteins within Aspergillus nidulans.
AB  - Endogenously tagging proteins with green fluorescent protein (GFP) enables the
      visualization of the tagged protein using live cell microscopy. GFP-tagging is
      widely utilized to study biological processes in model experimental organisms
      including filamentous fungi such as Aspergillus nidulans. Many strains of A.
      nidulans have therefore been generated with different proteins endogenously
      tagged with GFP. To further enhance experimental approaches based upon GFP
      tagging, we have adapted the GFP Binding Protein (GBP) system for A. nidulans.
      GBP is a genetically encoded Llama single chain antibody against GFP which binds
      GFP with high affinity. Using gene replacement approaches, it is therefore
      possible to link GBP to anchor proteins, which will then retarget GFP-tagged
      proteins away from their normal location to the location of the anchor-GBP
      protein. To facilitate this approach in A. nidulans, we made four base plasmid
      cassettes that can be used to generate gene replacement GBP-tagging constructs by
      utilizing fusion PCR. Using these base cassettes, fusion PCR, and gene targeting
      approaches, we generated strains with SPA10-GBP and Tom20-GBP gene replacements.
      These strains enabled test targeting of GFP-tagged proteins to septa or to the
      surface of mitochondria respectively. SPA10-GBP is shown to effectively target
      GFP-tagged proteins to both forming and mature septa. Tom20-GBP has a higher
      capacity to retarget GFP-tagged proteins being able to relocate all Nup49-GFP
      from its location within nuclear pore complexes (NPCs) to the cytoplasm in
      association with mitochondria. Notably, removal of Nup49-GFP from NPCs causes
      cold sensitivity as does deletion of the nup49 gene. The cassette constructs
      described facilitate experimental approaches to generate precise protein-protein
      linkages in fungi. The A. nidulans SPA10-GBP and Tom20-GBP strains can be
      utilized to modulate other GFP-tagged proteins of interest.

PMID- 29194454
TI  - Development of a tissue-specific ribosome profiling approach in Drosophila
      enables genome-wide evaluation of translational adaptations.
AB  - Recent advances in next-generation sequencing approaches have revolutionized our
      understanding of transcriptional expression in diverse systems. However,
      measurements of transcription do not necessarily reflect gene translation, the
      process of ultimate importance in understanding cellular function. To circumvent
      this limitation, biochemical tagging of ribosome subunits to isolate ribosome
      associated mRNA has been developed. However, this approach, called TRAP, lacks
      quantitative resolution compared to a superior technology, ribosome profiling.
      Here, we report the development of an optimized ribosome profiling approach in
      Drosophila. We first demonstrate successful ribosome profiling from a specific
      tissue, larval muscle, with enhanced resolution compared to conventional TRAP
      approaches. We next validate the ability of this technology to define genome-wide
      translational regulation. This technology is leveraged to test the relative
      contributions of transcriptional and translational mechanisms in the postsynaptic
      muscle that orchestrate the retrograde control of presynaptic function at the
      neuromuscular junction. Surprisingly, we find no evidence that significant
      changes in the transcription or translation of specific genes are necessary to
      enable retrograde homeostatic signaling, implying that post-translational
      mechanisms ultimately gate instructive retrograde communication. Finally, we show
      that a global increase in translation induces adaptive responses in both
      transcription and translation of protein chaperones and degradation factors to
      promote cellular proteostasis. Together, this development and validation of
      tissue-specific ribosome profiling enables sensitive and specific analysis of
      translation in Drosophila.

PMID- 29194457
TI  - Olfactory coding in the turbulent realm.
AB  - Long-distance olfactory search behaviors depend on odor detection dynamics. Due
      to turbulence, olfactory signals travel as bursts of variable concentration and
      spacing and are characterized by long-tail distributions of odor/no-odor events,
      challenging the computing capacities of olfactory systems. How animals encode
      complex olfactory scenes to track the plume far from the source remains unclear.
      Here we focus on the coding of the plume temporal dynamics in moths. We compare
      responses of olfactory receptor neurons (ORNs) and antennal lobe projection
      neurons (PNs) to sequences of pheromone stimuli either with white-noise patterns
      or with realistic turbulent temporal structures simulating a large range of
      distances (8 to 64 m) from the odor source. For the first time, we analyze what
      information is extracted by the olfactory system at large distances from the
      source. Neuronal responses are analyzed using linear-nonlinear models fitted with
      white-noise stimuli and used for predicting responses to turbulent stimuli. We
      found that neuronal firing rate is less correlated with the dynamic odor time
      course when distance to the source increases because of improper coding during
      long odor and no-odor events that characterize large distances. Rapid adaptation
      during long puffs does not preclude however the detection of puff transitions in
      PNs. Individual PNs but not individual ORNs encode the onset and offset of odor
      puffs for any temporal structure of stimuli. A higher spontaneous firing rate
      coupled to an inhibition phase at the end of PN responses contributes to this
      coding property. This allows PNs to decode the temporal structure of the odor
      plume at any distance to the source, an essential piece of information moths can
      use in their tracking behavior.

PMID- 29194459
TI  - Correction: Correction: The World Health Organization Fetal Growth Charts: A
      Multinational Longitudinal Study of Ultrasound Biometric Measurements and
      Estimated Fetal Weight.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1002284.].

PMID- 29194458
TI  - Evidence of increasing sedentarism in Mexico City during the last decade: Sitting
      time prevalence, trends, and associations with obesity and diabetes.
AB  - INTRODUCTION: Sedentary behaviors such as sitting time are associated with
      obesity and diabetes independently of total reported physical activity. This
      study aimed to describe the current sitting time/day prevalence and trends and to
      examine the association of sitting time with sociodemographic and clinical
      variables in Mexico City. METHODS: Two cross-sectional representative surveys in
      Mexico City were used for this analysis (2006: n = 1148 and 2015: n = 1329).
      Sedentary behavior questions from the International Physical Activity
      Questionnaire included time spent sitting on a weekday in the last week or on a
      Wednesday. Sitting time /day was divided into deciles, and participants in the
      highest decile (>= 420 minutes/day) were classified within the high sitting
      category; others were classified in the low sitting time category. Multivariate
      logistic regression was used to evaluate the associations of sitting time with
      sociodemographic and clinical indicators, controlling for confounders and testing
      for potential interactions. RESULTS: A total of 13.7% (2006) and 14.8% (2015)
      adults were classified in the highest sitting time category (>= 420 minutes/day).
      There was a significant increase in the average sitting time/day between the
      surveys (216.0 minutes in 2006 vs. 233.3 minutes in 2015, p < 0.001). In 2015,
      men, those aged 20-49 years, those in low-intensity jobs, students, and those
      with a high socioeconomic level were more likely to be in the highest sitting
      time category. Participants with overweight/obesity (OR = 2.37, 95% CI: 1.11,
      5.09) and those with high glucose levels (survey finding) (OR = 2.34, 95% CI:
      1.04, 5.25) were more likely to report sitting time in the highest category.
      DISCUSSION: Sitting time/day prevalence increased 8%, and average daily sitting
      minutes significantly increased by 8.2% (18 minutes) in the nine-year study
      period (2006-2015). Current public health policies should consider strategies not
      only for increasing physical activity levels, but also for reducing sitting
      time/day among the population as a measure to fight the growing epidemic of
      obesity and diabetes in Mexico.

PMID- 29194460
TI  - Dynamical system modeling to simulate donor T cell response to whole exome
      sequencing-derived recipient peptides: Understanding randomness in alloreactivity
      incidence following stem cell transplantation.
AB  - Quantitative relationship between the magnitude of variation in minor
      histocompatibility antigens (mHA) and graft versus host disease (GVHD)
      pathophysiology in stem cell transplant (SCT) donor-recipient pairs (DRP) is not
      established. In order to elucidate this relationship, whole exome sequencing
      (WES) was performed on 27 HLA matched related (MRD), & 50 unrelated donors (URD),
      to identify nonsynonymous single nucleotide polymorphisms (SNPs). An average
      2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0.01); resulting
      peptide antigens that may be presented on HLA class I molecules in each DRP were
      derived in silico (NetMHCpan ver2.0) and the tissue expression of proteins these
      were derived from determined (GTex). MRD DRP had an average 3,670 HLA-binding
      alloreactive peptides, putative mHA (pmHA) with an IC50 of <500 nM, and URD, had
      5,386 (p<0.01). To simulate an alloreactive donor cytotoxic T cell response, the
      array of pmHA in each patient was considered as an operator matrix modifying a
      hypothetical cytotoxic T cell clonal vector matrix; each responding T cell
      clone's proliferation was determined by the logistic equation of growth,
      accounting for HLA binding affinity and tissue expression of each alloreactive
      peptide. The resulting simulated organ-specific alloreactive T cell clonal growth
      revealed marked variability, with the T cell count differences spanning orders of
      magnitude between different DRP. Despite an estimated, uniform set of constants
      used in the model for all DRP, and a heterogeneously treated group of patients,
      higher total and organ-specific T cell counts were associated with cumulative
      incidence of moderate to severe GVHD in recipients. In conclusion, exome wide
      sequence differences and the variable alloreactive peptide binding to HLA in each
      DRP yields a large range of possible alloreactive donor T cell responses. Our
      findings also help understand the apparent randomness observed in the development
      of alloimmune responses.

PMID- 29194461
TI  - Evaluation and validation of commercial antibodies for the detection of Shb.
AB  - Antibodies are among the most important tools for protein detection but, prior to
      their usage, proper validation of their appropriateness for given applications is
      required. The utility of an antibody depends on its sensitivity and specificity.
      We studied these two aspects in a panel of commercial antibodies against Shb, a
      platform protein involved in receptor tyrosine kinase signalling, but the
      function of which is still incompletely understood. Several of the antibodies
      showed shortcomings or were not acceptable for detection of the endogenous
      protein. The few that could detect Shb were doing so in either western blotting
      or immunoprecipitation experiments but a given antibody could not work in both
      applications. This article provides a resource for the available molecular tools
      that can be used in future research on Shb.

PMID- 29194462
TI  - New strategies for the development of lipid-lowering therapies to reduce
      cardiovascular risk.
AB  - The very high occurrence of cardiovascular events presents a major public health
      issue, because treatment remains suboptimal. Lowering LDL cholesterol (LDL-C)
      with statins or ezetimibe in combination with a statin reduces major adverse
      cardiovascular events. The cardiovascular risk reduction in relation to the
      absolute LDL-C reduction is linear for most interventions without evidence of
      attenuation or increase in risk at low LDL-C levels. Opportunities for innovation
      in dyslipidaemia treatment should address the substantial risk of lipid
      associated cardiovascular events among patients optimally treated per guidelines
      but who cannot achieve LDL-C goals and who could benefit from additional LDL-C
      lowering therapy or experience side effects of statins. Fresh approaches are
      needed to identify promising drug targets early and develop them efficiently. The
      Cardiovascular Round Table of the European Society of Cardiology (ESC) convened a
      workshop to discuss new lipid-lowering strategies for cardiovascular risk
      reduction. Opportunities to improve treatment approaches and the efficient study
      of new therapies were explored. Circulating biomarkers may not be fully reliable
      proxy indicators of the relationship between treatment effect and clinical
      outcome. Mendelian randomization studies may better inform development strategies
      and refine treatment targets before Phase 3. Trials should match the drug to
      appropriate lipid and patient profile, and guidelines may move towards a
      precision-based approach to individual patient management. Stakeholder
      collaboration is needed to ensure continued innovation and better international
      coordination of both regulatory aspects and guidelines. It should be noted that
      risk may also be addressed through increased attention to other risk factors such
      as smoking, hypertension, overweight, and inactivity.

PMID- 29194464
TI  - Computer-aided biomarker discovery for precision medicine: data resources, models
      and applications.
AB  - Biomarkers are a class of measurable and evaluable indicators with the potential
      to predict disease initiation and progression. In contrast to disease-associated
      factors, biomarkers hold the promise to capture the changeable signatures of
      biological states. With methodological advances, computer-aided biomarker
      discovery has now become a burgeoning paradigm in the field of biomedical
      science. In recent years, the 'big data' term has accumulated for the
      systematical investigation of complex biological phenomena and promoted the
      flourishing of computational methods for systems-level biomarker screening.
      Compared with routine wet-lab experiments, bioinformatics approaches are more
      efficient to decode disease pathogenesis under a holistic framework, which is
      propitious to identify biomarkers ranging from single molecules to molecular
      networks for disease diagnosis, prognosis and therapy. In this review, the
      concept and characteristics of typical biomarker types, e.g. single molecular
      biomarkers, module/network biomarkers, cross-level biomarkers, etc., are
      explicated on the guidance of systems biology. Then, publicly available data
      resources together with some well-constructed biomarker databases and knowledge
      bases are introduced. Biomarker identification models using mathematical, network
      and machine learning theories are sequentially discussed. Based on network
      substructural and functional evidences, a novel bioinformatics model is
      particularly highlighted for microRNA biomarker discovery. This article aims to
      give deep insights into the advantages and challenges of current computational
      approaches for biomarker detection, and to light up the future wisdom toward
      precision medicine and nation-wide healthcare.

PMID- 29194463
TI  - Efficacy of Endoscopic Balloon Dilation for Small Bowel Strictures in Patients
      With Crohn's Disease: A Nationwide, Multi-centre, Open-label, Prospective Cohort
      Study.
AB  - Background and Aims: Endoscopic balloon dilation [EBD] is an alternative to
      surgery for Crohn's strictures. However, there have been no prospective studies
      of EBD for small bowel strictures in patients with Crohn's disease [CD]. The aim
      of this study was to clarify the efficacy and safety of EBD using balloon
      assisted enteroscopy for small bowel strictures in CD. Methods: This was a
      nationwide, multi-centre, open-label, prospective cohort study. The subjects were
      CD patients with at least one symptom [abdominal pain, abdominal bloating,
      nausea] attributable to small bowel stricture. The primary endpoint related to
      short-term outcomes was the level of improvement of symptoms evaluated using a 10
      cm visual analogue scale [VAS]. Cases in which VAS scores for all symptoms
      improved 4 weeks after EBD compared with baseline were considered to have short
      term symptomatic improvement. Factors related to short-term treatment outcomes
      and safety were investigated as secondary endpoints. Results: A total of 112
      patients were enrolled. Seventeen were later excluded because they did not meet
      the criteria, and the analysis was conducted with the remaining 95 patients. Of
      these 95 patients, procedure failure occurred in six [6.3%], and short-term
      symptomatic improvement was achieved in 66 patients [69.5%]. Adverse events were
      seen in five patients [5%] and all of these improved with conservative treatment.
      A large dilation diameter of the balloon was a factor contributing to the success
      of EBD. Conclusions: EBD using balloon-assisted enteroscopy for small bowel
      strictures in CD patients was shown to be an effective and safe procedure.
      Clinical trial registry: UMIN000005946.

PMID- 29194465
TI  - Rehabilitation in dementia care.
AB  - Multidisciplinary rehabilitation is increasingly accepted as valuable in the
      management of chronic disease. Whereas traditional rehabilitation models focussed
      on recovery, maintaining independence and delaying functional decline are now
      considered worthwhile aims even where full recovery is not feasible. Despite
      this, rehabilitation is notably absent from dementia care literature and
      practice. People with dementia report frustration with the lack of availability
      of structured post-diagnosis pathways like those offered for other conditions.
      Alternative terms such as 're-ablement' are used to refer to rehabilitation-like
      services, but lack an evidence-base to guide care. This commentary will discuss
      possible reasons for the resistance to accept multidisciplinary rehabilitation as
      part of dementia care, and identifies the value of doing so for people with
      dementia, their families, and for health professionals.

PMID- 29194466
TI  - Genome Context Viewer: visual exploration of multiple annotated genomes using
      microsynteny.
AB  - Summary: The Genome Context Viewer is a visual data-mining tool that allows users
      to search across multiple providers of genome data for regions with similarly
      annotated content that may be aligned and visualized at the level of their shared
      functional elements. By handling ordered sequences of gene family memberships as
      a unit of search and comparison, the user interface enables quick and intuitive
      assessment of the degree of gene content divergence and the presence of various
      types of structural events within syntenic contexts. Insights into functionally
      significant differences seen at this level of abstraction can then serve to
      direct the user to more detailed explorations of the underlying data in other
      interconnected, provider-specific tools. Availability and implementation: GCV is
      provided under the GNU General Public License version 3 (GPL-3.0). Source code is
      available at https://github.com/legumeinfo/lis_context_viewer. Contact:
      adf@ncgr.org. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29194467
TI  - Sleep hygiene education as a treatment of insomnia: a systematic review and meta
      analysis.
AB  - Background: Sleep hygiene education (SHE) is commonly used as a treatment of
      insomnia in general practice. Whether SHE or cognitive-behavioural therapy for
      insomnia (CBT-I), a treatment with stronger evidence base, should be provided
      first remains unclear. Objective: To review the efficacy of SHE for poor sleep or
      insomnia. Methods: We systematically searched six key electronic databases up
      until May 2017. Two researchers independently selected relevant publications,
      extracted data and evaluated methodological quality according to the Cochrane
      criteria. Results: Twelve of 15 studies compared SHE with CBT-I, three with
      mindfulness-based therapy, but none with sham or no treatment. General knowledge
      about sleep, substance use, regular exercise and bedroom arrangement were
      commonly covered; sleep-wake regularity and avoidance of daytime naps in seven
      programs, but stress management in only five programs. Major findings include (i)
      there were significant pre- to post-treatment improvements following SHE, with
      small to medium effect size; (ii) SHE was significantly less efficacious than CBT
      I, with difference in effect size ranging from medium to large; (iii) pre- to
      post-treatment improvement and SHE-CBT-I difference averaged at 5% and 8% in
      sleep-diary-derived sleep efficiency, respectively, and two points in Pittsburgh
      Sleep Quality Index; (iv) only subjective measures were significant and (v) no
      data on acceptability, adherence, understanding and cost-effectiveness.
      Conclusions: Although SHE is less effective than CBT-I, unanswered methodological
      and implementation issues prevent a firm conclusion to be made on whether SHE has
      a role in a stepped-care model for insomnia in primary care.

PMID- 29194468
TI  - Characteristics of Faecal Microbiota in Paediatric Crohn's Disease and Their
      Dynamic Changes During Infliximab Therapy.
AB  - Background: Crohn's disease [CD] is known to be associated with gut microbial
      dysbiosis. Infliximab [IFX] is increasingly used to treat paediatric CD; however,
      it is not clear how the gut microbiota is modified during IFX treatment. The aim
      of this study was to characterise the faecal microbiota community composition in
      paediatric CD patients and to assess its dynamic changes during IFX therapy.
      Methods: A 16S rRNA sequencing approach was applied to determine the compositions
      of microbial communities in faecal samples. The composition and function of the
      faecal microbiota were compared between CD patients and healthy controls.
      Results: Characteristics of faecal microbiome composition in paediatric CD
      patients before IFX treatment were represented by a lower biodiversity, a gain in
      Enterococcus, and a significant loss in multiple short-chain fatty acid [SCFA]
      producing bacteria, including Anaerostipes, Blautia, Coprococcus,
      Faecalibacterium, Lachnospira, Odoribacter, Roseburia, Ruminococcus, and
      Sutterella. Additionally, alterations were observed in metabolic functions of the
      gut microbial community in CD. IFX treatment increased the biodiversity of gut
      microbiota and shifted its composition as well as its functional capabilities in
      the paediatric CD patients toward a healthy status. However, multiple SCFA
      producing taxa were not significantly expanded. The sustained response of
      paediatric CD patients to IFX was associated with abundance of SCFA-producing
      bacteria. Conclusions: A lower biodiversity with alterations in the composition
      and function of faecal microbial community, characterising gut microbial
      dysbiosis, was observed in Chinese paediatric CD patients. IFX diminished the CD
      associated gut microbial dysbiosis but was deficient in increasing certain SCFA
      producing taxa.

PMID- 29194469
TI  - bioBakery: a meta'omic analysis environment.
AB  - Summary: bioBakery is a meta'omic analysis environment and collection of
      individual software tools with the capacity to process raw shotgun sequencing
      data into actionable microbial community feature profiles, summary reports, and
      publication-ready figures. It includes a collection of pre-configured analysis
      modules also joined into workflows for reproducibility. Availability and
      implementation: bioBakery (http://huttenhower.sph.harvard.edu/biobakery) is
      publicly available for local installation as individual modules and as a virtual
      machine image. Each individual module has been developed to perform a particular
      task (e.g. quantitative taxonomic profiling or statistical analysis), and they
      are provided with source code, tutorials, demonstration data, and validation
      results; the bioBakery virtual image includes the entire suite of modules and
      their dependencies pre-installed. Images are available for both Amazon EC2 and
      Google Compute Engine. All software is open source under the MIT license.
      bioBakery is actively maintained with a support group at biobakery
      users@googlegroups.com and new tools being added upon their release. Contact:
      chuttenh@hsph.harvard.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29194471
TI  - Atrial septal defects: even simple congenital heart diseases can be complicated.

PMID- 29194470
TI  - iDINGO-integrative differential network analysis in genomics with Shiny
      application.
AB  - Motivation: Differential network analysis is an important way to understand
      network rewiring involved in disease progression and development. Building
      differential networks from multiple 'omics data provides insight into the
      holistic differences of the interactive system under different patient-specific
      groups. DINGO was developed to infer group-specific dependencies and build
      differential networks. However, DINGO and other existing tools are limited to
      analyze data arising from a single platform, and modeling each of the multiple
      'omics data independently does not account for the hierarchical structure of the
      data. Results: We developed the iDINGO R package to estimate group-specific
      dependencies and make inferences on the integrative differential networks,
      considering the biological hierarchy among the platforms. A Shiny application has
      also been developed to facilitate easier analysis and visualization of results,
      including integrative differential networks and hub gene identification across
      platforms. Availability and implementation: R package is available on CRAN
      (https://cran.r-project.org/web/packages/iDINGO) and Shiny application at
      https://github.com/MinJinHa/iDINGO. Contact: mjha@mdanderson.org. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29194472
TI  - ThetaMater: Bayesian estimation of population size parameter theta from genomic
      data.
AB  - Summary: We describe ThetaMater, an open source R package comprising a suite of
      functions for efficient and scalable Bayesian estimation of the population size
      parameter theta from genomic data. Availability and implementation: ThetaMater is
      available at GitHub (https://github.com/radamsRHA/ThetaMater). Contact:
      todd.castoe@uta.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29194473
TI  - ESMO Consensus Conference on malignant lymphoma: general perspectives and
      recommendations for the clinical management of the elderly patient with malignant
      lymphoma.
AB  - The European Society for Medical Oncology (ESMO) consensus conference on mature B
      cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015
      in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading
      experts. The aim of the conference was to develop recommendations on critical
      subjects difficult to consider in detail in the ESMO Clinical Practice
      Guidelines. The following areas were identified: (1) the elderly patient, (2)
      prognostic factors suitable for clinical use, and (3) the 'ultra-high-risk'
      group. Before the conference, the expert panel was divided into three working
      groups; each group focused on one of these areas in order to address clinically
      relevant questions relating to that topic. All relevant scientific literature, as
      identified by the experts, was reviewed in advance. During the consensus
      conference, each working group developed recommendations to address each of the
      four questions assigned to their group. These recommendations were presented to
      the entire panel and a consensus was reached. This consensus, which was further
      developed in continuous post-meeting discussions, formed the basis of three
      manuscripts, each covering one of the three key areas identified. This manuscript
      presents the consensus recommendations regarding the clinical management of
      elderly patients diagnosed with malignant lymphoma. Four clinically-relevant
      topics identified by the panel were: 1) how to define patient fitness, 2)
      assessing quality of life, 3) diagnostic work-up and 4) clinical management of
      elderly patients with lymphoma. Each of these key topics is addressed in the
      context of five different lymphoma entities, namely: CLL, follicular lymphoma,
      mantle cell lymphoma, peripheral T-cell lymphoma and diffuse large B-cell
      lymphoma. Results, including a summary of evidence supporting each
      recommendation, are detailed in this manuscript.

PMID- 29194475
TI  - Analysis of the Strength of Legal Firearms Restrictions for Perpetrators of
      Domestic Violence and Their Associations With Intimate Partner Homicide.
AB  - In this research, we estimate the association of firearm restrictions for
      domestic violence offenders with intimate partner homicides (IPHs) on the basis
      of the strength of the policies. We posit that the association of firearm laws
      with IPHs depends on the following characteristics of the laws: 1) breadth of
      coverage of high-risk individuals and situations restricted; 2) power to compel
      firearm surrender or removal from persons prohibited from having firearms; and 3)
      systems of accountability that prevent those prohibited from doing so from
      obtaining guns. We conducted a quantitative policy evaluation using annual state
      level data from 1980 through 2013 for 45 US states. Based on the results of a
      series of robust, negative binomial regression models with state fixed effects,
      domestic violence restraining order firearm-prohibition laws are associated with
      10% reductions in IPH. Statistically significant protective associations were
      evident only when restraining order prohibitions covered dating partners (-11%)
      and ex parte orders (-12%). Laws prohibiting access to those convicted of
      nonspecific violent misdemeanors were associated with a 24% reduction in IPH
      rates; there was no association when prohibitions were limited to domestic
      violence. Permit-to-purchase laws were associated with 10% reductions in IPHs.
      These findings should inform policymakers considering laws to maximize
      protections against IPH.

PMID- 29194474
TI  - Power Analysis for Genetic Association Test (PAGEANT) provides insights to
      challenges for rare variant association studies.
AB  - Motivation: Genome-wide association studies are now shifting focus from analysis
      of common to rare variants. As power for association testing for individual rare
      variants may often be low, various aggregate level association tests have been
      proposed to detect genetic loci. Typically, power calculations for such tests
      require specification of large number of parameters, including effect sizes and
      allele frequencies of individual variants, making them difficult to use in
      practice. We propose to approximate power to a varying degree of accuracy using a
      smaller number of key parameters, including the total genetic variance explained
      by multiple variants within a locus. Results: We perform extensive simulation
      studies to assess the accuracy of the proposed approximations in realistic
      settings. Using these simplified power calculations, we develop an analytic
      framework to obtain bounds on genetic architecture of an underlying trait given
      results from genome-wide association studies with rare variants. Finally, we
      provide insights into the required quality of annotation/functional information
      for identification of likely causal variants to make meaningful improvement in
      power. Availability and implementation: A shiny application that allows a variety
      of Power Analysis of GEnetic AssociatioN Tests (PAGEANT), in R is made publicly
      available at https://andrewhaoyu.shinyapps.io/PAGEANT/. Contact:
      nilanjan@jhu.edu. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29194477
TI  - Regulatory feedback loops bridge the human gene regulatory network and regulate
      carcinogenesis.
AB  - The development of disease involves a systematic disturbance inside cells and is
      associated with changes in the interactions or regulations among genes forming
      biological networks. The bridges inside a network are critical in shortening the
      distances between nodes. We observed that, inside the human gene regulatory
      network, one strongly connected core bridged the whole network. Other regulations
      outside the core formed a weakly connected component surrounding the core like a
      peripheral structure. Furthermore, the regulatory feedback loops (FBLs) inside
      the core compose an interface-like structure between the core and periphery. We
      then denoted the regulatory FBLs as the interface core. Notably, both the cancer
      associated and essential biomolecules and regulations were significantly
      overrepresented in the interface core. These results implied that the interface
      core is not only critical for the network structure but central in cellular
      systems. Furthermore, the enrichment of the cancer-associated and essential
      regulations in the interface core might be attributed to its bridgeness in the
      network. More importantly, we identified one regulatory FBL between HNF4A and
      NR2F2 that possesses the highest bridgeness in the interface core. Further
      investigation suggested that the disturbance of the HNF4A-NR2F2 FBL might protect
      tumor cells from apoptotic processes. Our results emphasize the relevance of the
      regulatory network properties to cellular systems and might reveal a critical
      role of the interface core in cancer.

PMID- 29194476
TI  - RecoverY: k-mer-based read classification for Y-chromosome-specific sequencing
      and assembly.
AB  - Motivation: The haploid mammalian Y chromosome is usually under-represented in
      genome assemblies due to high repeat content and low depth due to its haploid
      nature. One strategy to ameliorate the low coverage of Y sequences is to
      experimentally enrich Y-specific material before assembly. As the enrichment
      process is imperfect, algorithms are needed to identify putative Y-specific reads
      prior to downstream assembly. A strategy that uses k-mer abundances to identify
      such reads was used to assemble the gorilla Y. However, the strategy required the
      manual setting of key parameters, a time-consuming process leading to sub-optimal
      assemblies. Results: We develop a method, RecoverY, that selects Y-specific reads
      by automatically choosing the abundance level at which a k-mer is deemed to
      originate from the Y. This algorithm uses prior knowledge about the Y chromosome
      of a related species or known Y transcript sequences. We evaluate RecoverY on
      both simulated and real data, for human and gorilla, and investigate its
      robustness to important parameters. We show that RecoverY leads to a vastly
      superior assembly compared to alternate strategies of filtering the reads or
      contigs. Compared to the preliminary strategy used by Tomaszkiewicz et al., we
      achieve a 33% improvement in assembly size and a 20% improvement in the NG50,
      demonstrating the power of automatic parameter selection. Availability and
      implementation: Our tool RecoverY is freely available at
      https://github.com/makovalab-psu/RecoverY. Contact: kmakova@bx.psu.edu or
      pashadag@cse.psu.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29194478
TI  - Male Neonate with Legionellosis.
AB  - Legionellaceae are composed of a single genus, Legionella, which is currently
      comprised of over 52 species. L. pneumophila, L. micdadei, L. longbeachae, and L.
      dumoffi are clinically considered the most important, with L. pneumophila causing
      >90%1,7 of cases of legionnaires disease (LD). Since LD's recognition in 1976
      following an outbreak of pneumonia involving delegates of an American Legion
      convention in Philadelphia, there has been increased awareness and importance of
      the isolation, detection, and reporting of these cases. Herein we describe the
      unfortunate case of a 7 month old boy with undiagnosed LD that lead to
      respiratory insufficiency, sepsis, multisystem organ failure and death.
      Laboratory investigation methods, and clinical and pathological findings are
      discussed.

PMID- 29194479
TI  - Emergence of an MDR Klebsiella pneumoniae ST231 producing OXA-232 and RmtF in
      Switzerland.

PMID- 29194480
TI  - Clinical trial registry alone is not adequate: on the perception of possible
      endpoint switching and P-hacking.

PMID- 29194481
TI  - fusionDB: assessing microbial diversity and environmental preferences via
      functional similarity networks.

PMID- 29194482
TI  - TIMP-1: is surrogate testing for extracellular matrix remodelling ready for
      clinical translation or only an Icelandic phenomenon?

PMID- 29194484
TI  - Robotic pericardial patch repair of the bronchus intermedius after bronchogenic
      cyst removal.
AB  - Bronchogenic cysts are often asymptomatic mediastinal masses that are usually
      diagnosed as incidental findings. Surgical resection can be performed with
      robotic surgery, and if repair of the airway is needed, this can be achieved by
      direct closure or by applying a pericardial patch. We present a case of a 45-year
      old woman diagnosed with a mass in the visceral mediastinum. She had undergone
      resection adopting a 4-armed, completely portal robotic technique. However, the
      removal of the cyst had led to a large tear in the bronchus intermedius. The
      bronchus was then repaired with a 2.4-cm-long pericardial patch sutured with the
      V-lock sutures. The entire procedure was performed in a total span of 189 min,
      and the patient was discharged on postoperative Day 2. The robotic platform, with
      articulated instruments, allowed complex suturing while conversion was not
      required. To our knowledge, the robotic surgery has not been applied in bronchial
      repairs by pericardial patches, and this case is the first of its kind.

PMID- 29194483
TI  - BmILF and i-motif structure are involved in transcriptional regulation of BmPOUM2
      in Bombyx mori.
AB  - Guanine-rich and cytosine-rich DNA can form four-stranded DNA secondary
      structures called G-quadruplex (G4) and i-motif, respectively. These structures
      widely exist in genomes and play important roles in transcription, replication,
      translation and protection of telomeres. In this study, G4 and i-motif structures
      were identified in the promoter of the transcription factor gene BmPOUM2, which
      regulates the expression of the wing disc cuticle protein gene (BmWCP4) during
      metamorphosis. Disruption of the i-motif structure by base mutation, anti-sense
      oligonucleotides (ASOs) or inhibitory ligands resulted in significant decrease in
      the activity of the BmPOUM2 promoter. A novel i-motif binding protein (BmILF) was
      identified by pull-down experiment. BmILF specifically bound to the i-motif and
      activated the transcription of BmPOUM2. The promoter activity of BmPOUM2 was
      enhanced when BmILF was over-expressed and decreased when BmILF was knocked-down
      by RNA interference. This study for the first time demonstrated that BmILF and
      the i-motif structure participated in the regulation of gene transcription in
      insect metamorphosis and provides new insights into the molecular mechanism of
      the secondary structures in epigenetic regulation of gene transcription.

PMID- 29194485
TI  - Self-protection of cytosolic malate dehydrogenase against oxidative stress in
      Arabidopsis.
AB  - Plant malate dehydrogenase (MDH) isoforms are found in different cell
      compartments and function in key metabolic pathways. It is well known that the
      chloroplastic NADP-dependent MDH activities are strictly redox regulated and
      controlled by light. However, redox dependence of other NAD-dependent MDH
      isoforms have been less studied. Here, we show by in vitro biochemical
      characterization that the major cytosolic MDH isoform (cytMDH1) is sensitive to
      H2O2 through sulfur oxidation of cysteines and methionines. CytMDH1 oxidation
      affects the kinetics, secondary structure, and thermodynamic stability of
      cytMDH1. Moreover, MS analyses and comparison of crystal structures between the
      reduced and H2O2-treated cytMDH1 further show that thioredoxin-reversible
      homodimerization of cytMDH1 through Cys330 disulfide formation protects the
      protein from overoxidation. Consistently, we found that cytosolic thioredoxins
      interact specifically with cytMDH in a yeast two-hybrid system. Importantly, we
      also show that cytosolic and chloroplastic, but not mitochondrial NAD-MDH
      activities are sensitive to H2O2 stress in Arabidopsis. NAD-MDH activities
      decreased both in a catalase2 mutant and in an NADP-thioredoxin reductase mutant,
      emphasizing the importance of the thioredoxin-reducing system to protect MDH from
      oxidation in vivo. We propose that the redox switch of the MDH activity
      contributes to adapt the cell metabolism to environmental constraints.

PMID- 29194486
TI  - Cortical Auditory-Evoked Responses in Preterm Neonates: Revisited by Spectral and
      Temporal Analyses.
AB  - Characteristic preterm EEG patterns of "Delta-brushes" (DBs) have been reported
      in the temporal cortex following auditory stimuli, but their spatio-temporal
      dynamics remains elusive. Using 32-electrode EEG recordings and co-registration
      of electrodes' position to 3D-MRI of age-matched neonates, we explored the
      cortical auditory-evoked responses (AERs) after 'click' stimuli in 30 healthy
      neonates aged 30-38 post-menstrual weeks (PMW). (1) We visually identified
      auditory-evoked DBs within AERs in all the babies between 30 and 33 PMW and a
      decreasing response rate afterwards. (2) The AERs showed an increase in EEG power
      from delta to gamma frequency bands over the middle and posterior temporal
      regions with higher values in quiet sleep and on the right. (3) Time-frequency
      and averaging analyses showed that the delta component of DBs, which negatively
      peaked around 550 and 750 ms over the middle and posterior temporal regions,
      respectively, was superimposed with fast (alpha-gamma) oscillations and
      corresponded to the late part of the cortical auditory-evoked potential (CAEP), a
      feature missed when using classical CAEP processing. As evoked DBs rate and AERs
      delta to alpha frequency power decreased until full term, auditory-evoked DBs are
      thus associated with the prenatal development of auditory processing and may
      suggest an early emerging hemispheric specialization.

PMID- 29194488
TI  - Impact of unresolved neutropenia in patients with neutropenia and invasive
      aspergillosis: a post hoc analysis of the SECURE trial.
AB  - Background: Historically, baseline neutropenia and lack of neutrophil recovery
      have been associated with poor outcomes in invasive aspergillosis (IA). It is
      unclear how treatment with the new Aspergillus-active triazoles isavuconazole and
      voriconazole affects outcomes in neutropenic patients with IA. Methods: A post
      hoc analysis of the Phase 3 SECURE trial assessed patients with neutropenia
      (neutrophil count <0.5 * 109/L for >10 days at baseline) with IA
      (proven/probable) who had received either isavuconazole or voriconazole. The
      primary endpoint was all-cause mortality (ACM) through day 42. ACM in patients
      with resolved versus unresolved neutropenia at day 7 and overall success at end
      of treatment (EOT) were also assessed. Results: One hundred and forty-two
      patients with neutropenia and IA were included (isavuconazole n = 78,
      voriconazole n = 64). ACM through day 42 (primary endpoint), day 7 and EOT were
      higher for patients with unresolved versus resolved neutropenia at each timepoint
      (day 42, unresolved: 45.0% isavuconazole, 45.2% voriconazole; resolved: 5.0%
      isavuconazole, 5.9% voriconazole; day 7, unresolved: 31.0% isavuconazole, 29.8%
      voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; EOT, unresolved:
      48.6% isavuconazole, 36.4% voriconazole; resolved: 5.0% isavuconazole, 14.3%
      voriconazole). ACM was significantly higher for isavuconazole-treated patients
      with unresolved versus resolved neutropenia (day 7, P = 0.031; day 42, P < 0.001;
      EOT, P < 0.001). In voriconazole-treated patients, ACM was significantly higher
      among patients with unresolved versus resolved neutropenia at day 42 (P = 0.002)
      and numerically higher at day 7 and EOT (P > 0.05 for both). Conclusions:
      Isavuconazole had comparable efficacy and safety to voriconazole in neutropenic
      patients with IA. Resolution of neutropenia was associated with improved
      outcomes.

PMID- 29194487
TI  - Comparative Genomics of an Unusual Biogeographic Disjunction in the Cotton Tribe
      (Gossypieae) Yields Insights into Genome Downsizing.
AB  - Long-distance insular dispersal is associated with divergence and speciation
      because of founder effects and strong genetic drift. The cotton tribe
      (Gossypieae) has experienced multiple transoceanic dispersals, generating an
      aggregate geographic range that encompasses much of the tropics and subtropics
      worldwide. Two genera in the Gossypieae, Kokia and Gossypioides, exhibit a
      remarkable geographic disjunction, being restricted to the Hawaiian Islands and
      Madagascar/East Africa, respectively. We assembled and use de novo genome
      sequences to address questions regarding the divergence of these two genera from
      each other and from their sister-group, Gossypium. In addition, we explore
      processes underlying the genome downsizing that characterizes Kokia and
      Gossypioides relative to other genera in the tribe. Using 13,000 gene orthologs
      and synonymous substitution rates, we show that the two disjuncts last shared a
      common ancestor ~5 Ma, or half as long ago as their divergence from Gossypium. We
      report relative stasis in the transposable element fraction. In comparison to
      Gossypium, there is loss of ~30% of the gene content in the two disjunct genera
      and a history of genome-wide accumulation of deletions. In both genera, there is
      a genome-wide bias toward deletions over insertions, and the number of gene
      losses exceeds the number of gains by ~2- to 4-fold. The genomic analyses
      presented here elucidate genomic consequences of the demographic and
      biogeographic history of these closest relatives of Gossypium, and enhance their
      value as phylogenetic outgroups.

PMID- 29194490
TI  - The Response of Prostate Smooth Muscle Cells to Testosterone Is Determined by the
      Subcellular Distribution of the Androgen Receptor.
AB  - Androgen signaling in prostate smooth muscle cells (pSMCs) is critical for the
      maintenance of prostate homeostasis, the alterations of which are a central
      aspect in the development of pathological conditions. Testosterone can act
      through the classic androgen receptor (AR) in the cytoplasm, eliciting genomic
      signaling, or through different types of receptors located at the plasma membrane
      for nongenomic signaling. We aimed to find evidence of nongenomic testosterone
      signaling mechanisms in pSMCs and their participation in cell proliferation,
      differentiation, and the modulation of the response to lipopolysaccharide. We
      demonstrated that pSMCs can respond to testosterone by a rapid activation of
      ERK1/2 and Akt. Furthermore, a pool of ARs localized at the cell surface of pSMCs
      is responsible for a nongenomic testosterone-induced increase in cell
      proliferation. Through membrane receptor stimulation, testosterone favors a
      muscle phenotype, indicated by an increase in smooth muscle markers. We also
      showed that the anti-inflammatory effects of testosterone, capable of attenuating
      lipopolysaccharide-induced proinflammatory actions, are promoted only by
      receptors located inside the cell. We postulate that testosterone might perform
      prohomeostatic effects through intracellular-initiated mechanisms by modulating
      cell proliferation and inflammation, whereas some pathological,
      hyperproliferative actions would be induced by membrane-initiated nongenomic
      signaling in pSMCs.

PMID- 29194489
TI  - mirDIP 4.1-integrative database of human microRNA target predictions.
AB  - MicroRNAs are important regulators of gene expression, achieved by binding to the
      gene to be regulated. Even with modern high-throughput technologies, it is
      laborious and expensive to detect all possible microRNA targets. For this reason,
      several computational microRNA-target prediction tools have been developed, each
      with its own strengths and limitations. Integration of different tools has been a
      successful approach to minimize the shortcomings of individual databases. Here,
      we present mirDIP v4.1, providing nearly 152 million human microRNA-target
      predictions, which were collected across 30 different resources. We also
      introduce an integrative score, which was statistically inferred from the
      obtained predictions, and was assigned to each unique microRNA-target interaction
      to provide a unified measure of confidence. We demonstrate that integrating
      predictions across multiple resources does not cumulate prediction bias toward
      biological processes or pathways. mirDIP v4.1 is freely available at
      http://ophid.utoronto.ca/mirDIP/.

PMID- 29194492
TI  - Commentary on: Cannula vs Sharp Needle for Placement of Soft Tissue Fillers: An
      Observational Cadaver Study.

PMID- 29194491
TI  - Healthcare providers' perceptions of a situational awareness display for
      emergency department resuscitation: a simulation qualitative study.
AB  - Importance: Emergency resuscitation of critically ill patients can challenge team
      communication and situational awareness. Tools facilitating team performance may
      enhance patient safety. Objectives: To determine resuscitation team members'
      perceptions of the Situational Awareness Display's utility. Design: We conducted
      focus groups with healthcare providers during Situational Awareness Display
      development. After simulations assessing the display, we conducted debriefs with
      participants. Setting: Dual site tertiary care level 1 trauma centre in Ottawa,
      Canada. Participants: We recruited by email physicians, nurses and respiratory
      therapist. Intervention: Situational Awareness Display, a visual cognitive aid
      that provides key clinical information to enhance resuscitation team
      communication and situational awareness. Main outcomes and measures: Themes
      emerging from focus groups and simulation debriefs. Three reviewers independently
      coded and analysed transcripts using content qualitative analysis. Results: We
      recruited a total of 33 participants in two focus groups (n = 20) and six
      simulation debriefs with three 4-5 member teams (n = 13). Majority of
      participants (10/13) strongly endorsed the Situational Awareness Display's
      utility in simulation (very or extremely useful). Focus groups and debrief themes
      included improved perception of patient data, comprehension of context and
      ability to project to future decisions. Participants described potentially
      positive and negative impacts on patient safety and positive impacts on provider
      performance and team communication. Participants expressed a need for easy data
      entry incorporated into clinical workflow and training on how to use the display.
      Conclusion: Emergency resuscitation team participants felt the Situational
      Awareness Display has potential to improve provider performance, team
      communication and situational awareness, ultimately enhancing quality of care.

PMID- 29194493
TI  - Not Your Garden-Variety Bacteremia: Gardnerella in an Immunocompromised Man.
AB  - Systemic Gardnerella infections are rare and usually associated with surgical
      instrumentation of the genitourinary tract. We present a case of symptomatic and
      transient Gardnerella bacteremia in a man with AIDS after a traumatic urinary
      catheter insertion.

PMID- 29194494
TI  - Impact of bundled payments on hip fracture outcomes: a nationwide population
      based study.
AB  - Objective: Establishing one price for all bundled services for a particular
      illness, which has become the key to healthcare reform efforts, is designed to
      encourage health professionals to coordinate their care for patients. Limited
      information is available, however, concerning whether bundled payments are
      associated with changes in patient outcomes. Nationwide longitudinal population
      based data were used to examine the effect of bundled payments on hip fracture
      outcomes. Design: An interrupted time series design with a comparison group.
      Setting: General acute care hospitals throughout Taiwan. Participants: A total of
      178 586 hip fracture patients admitted over the period 2007-12 identified from
      the Taiwan's National Health Insurance Research Database. Intervention: Bundled
      payments for hip fractures were implemented in Taiwan in January 2010. Main
      Outcome Measures: The 30-day unplanned readmission and postdischarge mortality.
      Segmented generalized estimating equation regression models were used after
      adjustment for trends, patient, physician and hospital characteristics to assess
      the effect of bundled payments on 30-day outcomes for hip fracture compared with
      a reference condition. Results: The 30-day unplanned readmission rate for hip
      fracture showed a relative decreasing trend after the implementation of bundled
      payments compared with the trend before the implementation relative to that of
      the reference condition. Conclusions: This finding might imply that the
      implementation of bundled payments encourages health professionals to coordinate
      their care, leading to reduced readmission for hip fracture.

PMID- 29194495
TI  - Reply: Clinical trial registry alone is not adequate: on the perception of
      possible endpoint switching and P-hacking.

PMID- 29194496
TI  - Cambial pinning relates wood anatomy to ecophysiology in the African tropical
      tree Maesopsis eminii.
AB  - A better understanding and prediction of the impact of changing climate on tree
      stem growth could greatly benefit from the combination of anatomical and
      ecophysiological knowledge, yet the majority of studies focus on one research
      field only. We propose an approach that combines the method of pinning (cambial
      wounding) to timestamp anatomical X-ray computed microtomography images with
      continuous measurements of sap flow and stem diameter variations. By pinning the
      cambium of well-watered and drought-treated young African tropical trees of the
      species Maesopsis eminii Engl. we could quantify wood formation during a specific
      period of time and relate it to tree physiology and prevailing microclimate.
      Integrating continuous plant measurements and high-frequency pinning proved very
      useful to visualize and quantify the effects on stem growth of drought in M.
      eminii. Wood formation completely stopped during drought, and was associated with
      a strong shrinkage in stem diameter. Next, an unexpected increase in stem
      diameter was observed during drought, probably caused by root pressure, but not
      accompanied by wood formation. Our proposed approach of combining continuous
      plant measurements with cambial pinning is very promising to relate ecophysiology
      to stem anatomy and to understand the mechanisms underlying tree stem growth and
      bridge the gaps between the two research fields.

PMID- 29194497
TI  - Comment on: Patients' preferences for anti-osteoporosis drug treatment: a cross
      European discrete choice experiment: reply.

PMID- 29194498
TI  - Commentary on: Modified Levator Muscle Resection Using Putterman Muller's Muscle
      Conjunctival Resection-Ptosis Clamp.

PMID- 29194501
TI  - Gene3D: Extensive prediction of globular domains in proteins.

PMID- 29194502
TI  - The secret dream laboratory.

PMID- 29194503
TI  - Distinct influence of specific versus global connectivity on the different
      Alzheimer's disease biomarkers.

PMID- 29194499
TI  - Emotion recognition associated with polymorphism in oxytocinergic pathway gene
      ARNT2.
AB  - The ability to correctly understand the emotional expression of another person is
      essential for social relationships and appears to be a partly inherited trait.
      The neuropeptides oxytocin and vasopressin have been shown to influence this
      ability as well as face processing in humans. Here, recognition of the emotional
      content of faces and voices, separately and combined, was investigated in 492
      subjects, genotyped for 25 single nucleotide polymorphisms (SNPs) in eight genes
      encoding proteins important for oxytocin and vasopressin neurotransmission. The
      SNP rs4778599 in the gene encoding aryl hydrocarbon receptor nuclear translocator
      2 (ARNT2), a transcription factor that participates in the development of
      hypothalamic oxytocin and vasopressin neurons, showed an association that
      survived correction for multiple testing with emotion recognition of audio-visual
      stimuli in women (n = 309). This study demonstrates evidence for an association
      that further expands previous findings of oxytocin and vasopressin involvement in
      emotion recognition.

PMID- 29194500
TI  - EANO guidelines for the diagnosis and treatment of ependymal tumors.
AB  - Ependymal tumors are rare CNS tumors and may occur at any age, but their
      proportion among primary brain tumors is highest in children and young adults.
      Thus, the level of evidence of diagnostic and therapeutic interventions is higher
      in the pediatric compared with the adult patient population.The diagnosis and
      disease staging is performed by craniospinal MRI. Tumor classification is
      achieved by histological and molecular diagnostic assessment of tissue specimens
      according to the World Health Organization (WHO) classification 2016. Surgery is
      the crucial initial treatment in both children and adults. In pediatric patients
      with intracranial ependymomas of WHO grades II or III, surgery is followed by
      local radiotherapy regardless of residual tumor volume. In adults, radiotherapy
      is employed in patients with anaplastic ependymoma WHO grade III, and in case of
      incomplete resection of WHO grade II ependymoma. Chemotherapy alone is reserved
      for young children <12 months and for adults with recurrent disease when further
      surgery and irradiation are no longer feasible. A gross total resection is the
      mainstay of treatment in spinal ependymomas, and radiotherapy is reserved for
      incompletely resected tumors. Nine subgroups of ependymal tumors across different
      anatomical compartments (supratentorial, posterior fossa, spinal) and patient
      ages have been identified with distinct genetic and epigenetic alterations, and
      with distinct outcomes. These findings may lead to more precise diagnostic and
      prognostic assessments, molecular subgroup-adapted therapies, and eventually new
      recommendations pending validation in prospective studies.

PMID- 29194504
TI  - MOG-antibody neuromyelitis optica spectrum disorder: is it a separate disease?

PMID- 29194505
TI  - Functional brain network architecture may route progression of Alzheimer's
      disease pathology.

PMID- 29194506
TI  - Imbalance of the direct and indirect pathways in focal dystonia: a balanced view.

PMID- 29194507
TI  - How far can biomarkers take us in neurodegenerative disorders?

PMID- 29194508
TI  - TMEM106B and myelination: rare leukodystrophy families reveal unexpected
      connections.

PMID- 29194509
TI  - The influence of increasing temperature and CO2 concentration on recent growth of
      old-growth larch: contrasting responses at leaf and stem processes derived from
      tree-ring width and stable isotopes.
AB  - Time series of tree-ring growth show significant increases since the early 1970s
      at the alpine tree line, with simultaneously increasing temperatures and
      atmospheric CO2 concentration. For a comprehensive understanding of this growth
      change, the physiological response patterns at both the leaf and stem level need
      to be separately analyzed and identified, and can be retrieved from tree-ring
      growth and isotope (delta13C, delta18O) series. In this study, we assessed the
      relative contribution of environmental factors to interannual tree-ring
      variability by multivariate linear mixed-effects models and the dual isotope
      approach on a dataset of tree-ring records of ~400-year-old larch (Larix decidua
      Mill.) from a non-water-limited high-elevation site in the Swiss Alps. The models
      suggest that summer temperatures and the recent lack of larch budmoth outbreaks
      were most important for explaining growth variations and trends, while a
      significant direct effect of the continuously increasing CO2 concentration could
      not be confirmed. In contrast, delta13C and delta18O, which are strongly
      influenced by fractionation changes in the leaf, clearly reflected the impact of
      air humidity (precipitation and vapor pressure deficit) and CO2 concentration:
      the increase in (delta13C-derived) intrinsic water-use efficiency over the second
      half of the 20th century suggests an increase in carbon assimilation as a result
      of enhanced CO2 concentration. The tree-ring delta18O largely reflected recent
      precipitation as source water, thus indicating a low variability in stomatal
      conductance, which was confirmed by the dual isotope approach. These leaf-level
      effects were not reflected in stem growth as they may have been masked by the
      temperature-caused growth limitation controlling the allocation of increased
      amounts of photosynthates into wood growth. Our approach demonstrates that the
      identification of different roles of environmental factors on leaf and stem
      processes helps to improve the assessment of site-specific changes of carbon
      fluxes and growth performance under future environmental conditions.

PMID- 29194510
TI  - Correlation of biologically effective dose and the tumor control in Stage I (<5
      cm) non-small cell lung cancer with stereotactic ablative radiotherapy: a single
      institutional cohort study.
AB  - Backgrounds: Stereotactic ablative radiotherapy (SABR) is one of the newly
      developed innovative radiotherapy and of which optimal dose prescription needs to
      be standardized. We aimed to investigate the dose-response relationship for
      patients with SABR. Methods: Fifty-three patients with Stage I non-small cell
      lung cancer patients, who underwent SABR between November 2006 and January 2015,
      were evaluated retrospectively. Thirteen patients (24.5%), who refused the
      surgery were included and 40 patients (75.5%) were medically inoperable at
      diagnosis. The median age was 74 years. The median SABR dose was 50 Gy in 3-8
      fractions and the median biologically effective dose (BED;alpha/beta = 10) was
      105.6 Gy (range: 60-160.53 Gy). Results: The median follow-up was 37.1 months.
      The 1 and 3 year local control rates were 91.7% and 85.1%. The 3 year overall and
      progression-free survival rate were 63.3% and 47.5%, respectively, and freedom
      from progression was 62.2%. Local control rate and 3-year overall survival
      according to tumor size was 100% and 79.4% in T1 tumors in a while 61.8% and 45%
      in T2a tumors. The 3-year local and regional control by BED10 was 79.4% and 69.4%
      in <=100 Gy vs. 89.1% and 100% in >100 Gy (P = 0.526, 0.004). Dyspnea more than
      Grade 3 was reported in six (11.3%) patients and Grade 1 chest pain was shown in
      five (9.4%) patients. Conclusions: The excellent regional control was conferred
      with a prescription of more than BED10 of 100 Gy, which also might be needed to
      achieve better local tumor control in T2a patients with tolerable lung function.

PMID- 29194511
TI  - Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in
      fission yeast.
AB  - Centromeric identity and chromosome segregation are determined by the precise
      centromeric targeting of CENP-A, the centromere-specific histone H3 variant. The
      significance of the amino-terminal domain (NTD) of CENP-A in this process remains
      unclear. Here, we assessed the functional significance of each residue within the
      NTD of CENP-A from Schizosaccharomyces pombe (SpCENP-A) and identified a proline
      rich 'GRANT' (Genomic stability-Regulating site within CENP-A N-Terminus) motif
      that is important for CENP-A function. Through sequential mutagenesis, we show
      that GRANT proline residues are essential for coordinating SpCENP-A centromeric
      targeting. GRANT proline-15 (P15), in particular, undergoes cis-trans
      isomerization to regulate chromosome segregation fidelity, which appears to be
      carried out by two FK506-binding protein (FKBP) family prolyl cis-trans
      isomerases. Using proteomics analysis, we further identified the SpCENP-A
      localizing chaperone Sim3 as a SpCENP-A NTD interacting protein that is dependent
      on GRANT proline residues. Ectopic expression of sim3+ complemented the
      chromosome segregation defect arising from the loss of these proline residues.
      Overall, cis-trans proline isomerization is a post-translational modification of
      the SpCENP-A NTD that confers precise propagation of centromeric integrity in
      fission yeast, presumably via targeting SpCENP-A to the centromere.

PMID- 29194512
TI  - Alcohol Relapse After Liver Transplantation for Alcoholic Cirrhosis-Impact on
      Liver Graft and Patient Survival: A Meta-analysis.
AB  - Aim: We performed meta-analysis to determine effect of alcohol relapse after
      liver transplantation (LT) for alcoholic cirrhosis on graft histology and
      survival. Methods: Studies were selected using following criteria: (a) LT for
      alcoholic cirrhosis, (b) reporting data on liver histology and/or patient
      survival among relapsers and abstainers, (c) minimum follow-up of 3 years. Random
      effects model was used to pool data to compare relapsers and abstainers on liver
      histology and patient survival. Results: On analysis of seven studies, pooled
      prevalence of self-reported alcohol relapse was 26.3% (18.0-36.7%) over median
      (range) follow-up of 6.0 (3.7-8.3) years, with annual alcohol relapse rate of
      4.7% (3.0-6.4%) for any alcohol use and 2.9% (0.5-5.3%) for heavy alcohol use.
      Relapsers compared to abstainers had higher odds for graft steatosis [4.1 (2.4
      6.9)], steatohepatitis [4.5 (1.4-14.2)], alcoholic hepatitis [9.3 (1.01-85)],
      advanced fibrosis or cirrhosis [8.4 (3.5-20)]. Relapsers were over 3-fold more
      likely to die at 10 years of follow-up: [3.67 (1.42-9.50)] without differences in
      overall or 5-year survival. Recurrent alcoholic cirrhosis occurring in 9% of
      biopsied patients and 2% of all transplants was responsible for about 20% of all
      deaths on follow-up after LT. Extra-hepatic malignancy, and cardiovascular events
      were common causes for patient mortality. Conclusion: Alcohol relapse after LT
      for alcoholic cirrhosis negatively impacts the graft and long-term patient
      survival. Studies are needed to develop strategies to reduce alcohol relapse
      after LT for alcoholic cirrhosis. Short Summary: Alcohol relapse in liver
      transplant recipients can negatively affect graft histology and patient survival.
      Strategies to reduce alcohol relapse are needed to preserve graft function?

PMID- 29194513
TI  - Composition of Anopheline (Diptera: Culicidae) Community and Its Seasonal
      Variation in Three Environments of the City of Puerto Iguazu, Misiones,
      Argentina.
AB  - In order to extend the knowledge of the composition of the anopheline community
      and the seasonal variation related to anthropogenic modifications in the city of
      Puerto Iguazu, adult females were captured between 2009 and 2012. Samples were
      collected in three environments with different degrees of anthropogenic
      modification: urban, periurban, and wild. Alpha diversity was evaluated as the
      'true' diversity of the species in each environment. Among environments, range
      abundance curves were used to compare the composition, abundance, and uniformity
      of species and cluster analysis was used to analyze the similarities and
      differences. The temporal distribution was analyzed and the relative abundance of
      the species captured was correlated with meteorological variables. A total of
      4,565 females, belonging to seven species: Anopheles albitarsis s.s. (Lynch
      Arribalzaga), Anopheles argyritarsis (Robineau-Desvoidy), Anopheles deaneorum
      (Rosa-Freitas), Anopheles fluminensis (Root), Anopheles mediopunctatus
      (Theobald), Anopheles strodei s.l. (Root), and Anopheles triannulatus s.l. (Neiva
      and Pinto) were captured. The wild environment showed higher abundance,
      diversity, and greater uniformity reflected on the less sharp area of the range
      abundance curve. Species richness was the same in the wild and periurban
      environments. Higher abundances were observed in summer during the months with
      higher temperatures. Although the wild environment showed greater Anopheles
      abundances and diversity, specific richness and species complementarity were
      similar among the three environments studied. Thus, the periurban environment
      would turn into a transition zone of great epidemiological importance due to the
      introduction of people in this environment, which represents a potential risk of
      malaria transmission in the area.

PMID- 29194515
TI  - State of The Art of Instrumentation in Experimental Nanodosimetry.
AB  - Nanodosimetry is a branch of dosimetry for investigation and modeling of the
      interaction pattern of ionizing radiation in nanometre site-sizes (at unit
      density), which dates back to the 1970's (Pszona S. A track ion counter.
      Proceedings of Fifth Symposium on Microdosimetry EUR 5452 d-e-f, Published by the
      Commission of the European Communities, Luxemburg, pp. 1107-1122 (1976)). To
      date, the different experimental approaches have lead to developing of three
      fully functional nanodosimeters: the Jet Counter operated at NCBJ, the Ion
      Counter operated at PTB and Startrack Counter operated at INFN-LNL. Descriptions
      of each nanodosimeter as well as of the techniques used to investigate the track
      structure of ionizing particles are presented.

PMID- 29194514
TI  - Mouse models of two missense mutations in actin-binding domain 1 of dystrophin
      associated with Duchenne or Becker muscular dystrophy.
AB  - Missense mutations in the dystrophin protein can cause Duchenne muscular
      dystrophy (DMD) or Becker muscular dystrophy (BMD) through an undefined
      pathomechanism. In vitro studies suggest that missense mutations in the N
      terminal actin-binding domain (ABD1) cause protein instability, and cultured
      myoblast studies reveal decreased expression levels that can be restored to wild
      type with proteasome inhibitors. To further elucidate the pathophysiology of
      missense dystrophin in vivo, we generated two transgenic mdx mouse lines
      expressing L54R or L172H mutant dystrophin, which correspond to missense
      mutations identified in human patients with DMD or BMD, respectively. Our
      biochemical, histologic and physiologic analysis of the L54R and L172H mice show
      decreased levels of dystrophin which are proportional to the phenotypic severity.
      Proteasome inhibitors were ineffective in both the L54R and L172H mice, yet mice
      homozygous for the L172H transgene were able to express even higher levels of
      dystrophin which caused further improvements in muscle histology and physiology.
      Given that missense dystrophin is likely being degraded by the proteasome but
      whole body proteasome inhibition was not possible, we screened for ubiquitin
      conjugating enzymes involved in targeting dystrophin to the proteasome. A
      myoblast cell line expressing L54R mutant dystrophin was screened with an siRNA
      library targeting E1, E2 and E3 ligases which identified Amn1, FBXO33, Zfand5 and
      Trim75. Our study establishes new mouse models of dystrophinopathy and identifies
      candidate E3 ligases that may specifically regulate dystrophin protein turnover
      in vivo.

PMID- 29194516
TI  - Deficits in Cortical Suppression During Vocalization are Associated With
      Structural Abnormalities in the Arcuate Fasciculus in Early Illness Schizophrenia
      and Clinical High Risk for Psychosis.
AB  - Self-generated speech produces a smaller N1 amplitude in the auditory-evoked
      potential than externally generated speech; this phenomenon is known as N1
      suppression. Schizophrenia patients show less N1-suppression than healthy
      controls. This failure to self-suppress may underlie patients' characteristic
      tendency to misattribute self-generated thoughts and actions to external sources.
      While the cause of N1-suppression deficits to speech in schizophrenia remains
      unclear, structural damage to the arcuate fasciculus is a candidate, due to its
      ostensible role in transmitting the efference copy of the motor plan to speak.
      Fifty-one patients with early illness schizophrenia (ESZ), 40 individuals at
      clinical high-risk for psychosis (CHR), and 59 healthy control (HC) participants
      underwent an electroencephalogram while they spoke and then listened to a
      recording of their speech. N1-suppression to the spoken sounds was calculated.
      Participants also underwent a diffusion-tensor imaging (DTI) scan, from which the
      arcuate fasciculus and pyramidal tract were extracted with deterministic
      tractography. ESZ patients exhibited significantly less N1-suppression to self
      generated speech than HC participants, with CHR participants exhibiting
      intermediate levels. ESZ patients also exhibited structural abnormalities in the
      arcuate fasciculus-specifically, reduced fractional anisotropy and increased
      radial diffusivity-relative to both HC and CHR. There were no between-group
      differences in the structural integrity of the pyramidal tract. Finally, level of
      N1-suppression was linearly related to the structural integrity of the arcuate
      fasciculus, but not the pyramidal tract, across groups. These results suggest
      that the self-suppression deficits to willed speech consistently observed in
      schizophrenia patients may be caused, at least in part, by structural damage to
      the arcuate fasciculus.

PMID- 29194517
TI  - A Switch and Wave of Neuronal Activity in the Cerebral Cortex During the First
      Second of Conscious Perception.
AB  - Conscious perception occurs within less than 1 s. To study events on this time
      scale we used direct electrical recordings from the human cerebral cortex during
      a conscious visual perception task. Faces were presented at individually titrated
      visual threshold for 9 subjects while measuring broadband 40-115 Hz gamma power
      in a total of 1621 intracranial electrodes widely distributed in both
      hemispheres. Surface maps and k-means clustering analysis showed initial
      activation of visual cortex for both perceived and non-perceived stimuli.
      However, only stimuli reported as perceived then elicited a forward-sweeping wave
      of activity throughout the cerebral cortex accompanied by large-scale network
      switching. Specifically, a monophasic wave of broadband gamma activation moves
      through bilateral association cortex at a rate of approximately 150 mm/s and
      eventually reenters visual cortex for perceived but not for non-perceived
      stimuli. Meanwhile, the default mode network and the initial visual cortex and
      higher association cortex networks are switched off for the duration of conscious
      stimulus processing. Based on these findings, we propose a new "switch-and-wave"
      model for the processing of consciously perceived stimuli. These findings are
      important for understanding normal conscious perception and may also shed light
      on its vulnerability to disruption by brain disorders.

PMID- 29194518
TI  - Coincidental ganglionated plexus modification during radiofrequency pulmonary
      vein isolation and post-ablation arrhythmia recurrence.
AB  - Aims: Vagal responses (VR) during left atrial ablation for atrial fibrillation
      (AF) treatment have been reported to be associated with less recurrences,
      presumably because they are a sign of ganglionated plexi modification. Our
      objective was to evaluate whether coincidentally elicited VR during left atrial
      ablation are associated with lower AF recurrence rates. Methods and results: This
      is a post hoc analysis of a prospective study of 291 patients with paroxysmal AF
      undergoing radiofrequency pulmonary vein isolation (PVI). Vagal responses were
      defined as episodes of heart rate <40 bpm or asystole lasting >5 s elicited
      during energy application. Sixty-eight patients (23.4%) had a VR during ablation.
      In Kaplan-Meier analysis, mean recurrence-free survival was 449 days (95%
      confidence interval 411-488) in patients with VR when compared with 435 days (95%
      confidence interval 415-455) in those without (P = 0.310). The 12-month
      recurrence rate estimates were 25 and 27%, respectively. In an unadjusted Cox
      model, VR was associated with an odds ratio for recurrence of 0.77 (95%
      confidence interval 0.46-1.28). Conclusion: Coincidentally elicited VR during
      radiofrequency PVI in patients with paroxysmal AF do not appear to be related to
      lower risk of arrhythmia recurrence. This may mean that, even if a VR is truly a
      sign of coincidental ablation of a ganglionated plexus, this does not necessarily
      mean that a therapeutic modification has been effected, at least to a degree
      associated with clinical benefit.

PMID- 29194519
TI  - Development of an Analytical Procedure for the Determination of Multiclass
      Compounds for Forensic Veterinary Toxicology.
AB  - Reported here is a new analytical multiclass method based on QuEChERS technique,
      which has proven to be effective in diagnosing fatal poisoning cases in animals.
      This method has been developed for the determination of analytes in liver samples
      comprising rodenticides, carbamate and organophosphorus pesticides, coccidiostats
      and mycotoxins. The procedure entails addition of acetonitrile and sodium acetate
      to 2 g of homogenized liver sample. The mixture was shaken intensively and
      centrifuged for phase separation, which was followed by an organic phase transfer
      into a tube containing sorbents (PSA and C18) and magnesium sulfate, then it was
      centrifuged, the supernatant was filtered and analyzed by liquid chromatography
      tandem mass spectrometry. A validation of the procedure was performed.
      Repeatability variation coefficients <15% have been achieved for most of the
      analyzed substances. Analytical conditions allowed for a successful separation of
      variety of poisons with the typical screening detection limit at <=10 MUg/kg
      levels. The method was used to investigate more than 100 animals poisoning
      incidents and proved that is useful to be used in animal forensic toxicology
      cases.

PMID- 29194521
TI  - Chylopericardium.

PMID- 29194522
TI  - Morphology and Polytene Chromosomes of a New Species of Simulium (Trichodagmia)
      (Diptera: Simuliidae) from the Espinhaco Mountains of Brazil.
AB  - The species richness of black flies in the Simulium (Trichodagmia) orbitale
      (Diptera: Simuliidae) species group is greatest in southern Brazil, where 9 of 19
      species are found. A new species in the S. orbitale group was collected during a
      survey of black flies in Minas Gerais state, Brazil, in the Espinhaco Mountains,
      an area rich in endemic taxa. The new species is morphologically similar to
      Simulium guianense Wise (Diptera: Simuliidae), the main vector of the causal
      agent of onchocerciasis in Brazil and Venezuela. It can be identified in the male
      by the unpatterned scutum and slightly concave ventral plate with a prominent
      median projection, in the female by the bilobate anal lobe, in the pupa by the 12
      slender gill filaments with nonsclerotized apices, branching in a rake-like
      pattern, and in the larva by the elongated abdominal segments V-VIII and
      ventrolaterally lobulate segment IX. The polytene chromosomes have one unique
      fixed inversion in the IS arm, relative to all other Brazilian members of the
      group, confirming the morphological evidence of a distinct species.

PMID- 29194520
TI  - Trajectories and Drivers of Genome Evolution in Surface-Associated Marine
      Phaeobacter.
AB  - The extent of genome divergence and the evolutionary events leading to speciation
      of marine bacteria have mostly been studied for (locally) abundant, free-living
      groups. The genus Phaeobacter is found on different marine surfaces, seems to
      occupy geographically disjunct habitats, and is involved in different biotic
      interactions, and was therefore targeted in the present study. The analysis of
      the chromosomes of 32 closely related but geographically spread Phaeobacter
      strains revealed an exceptionally large, highly syntenic core genome. The
      flexible gene pool is constantly but slightly expanding across all Phaeobacter
      lineages. The horizontally transferred genes mostly originated from bacteria of
      the Roseobacter group and horizontal transfer most likely was mediated by gene
      transfer agents. No evidence for geographic isolation and habitat specificity of
      the different phylogenomic Phaeobacter clades was detected based on the sources
      of isolation. In contrast, the functional gene repertoire and physiological
      traits of different phylogenomic Phaeobacter clades were sufficiently distinct to
      suggest an adaptation to an associated lifestyle with algae, to additional
      nutrient sources, or toxic heavy metals. Our study reveals that the evolutionary
      trajectories of surface-associated marine bacteria can differ significantly from
      free-living marine bacteria or marine generalists.

PMID- 29194523
TI  - Modified Levator Muscle Resection Using Putterman Muller's Muscle-Conjunctival
      Resection-Ptosis Clamp.
AB  - Background: The traditional technique for levator muscle resection includes a
      time-consuming dissection procedure that causes tissue trauma and swelling. The
      Putterman ptosis clamp has been popularly used in recent years for conjunctival
      mullerectomy. In this paper, we describe a modified surgical technique for ptosis
      treatment using the Putterman ptosis clamp. The modified technique improves the
      surgical results of levator muscle resection. Objectives: We performed a
      retrospective case-series study to determine the outcomes and complications
      associated with the use of the Putterman ptosis clamp in levator muscle
      resection. Methods: Adults aged >=18 years with moderate-to-severe ptosis
      underwent the modified technique for levator muscle resection. We first performed
      dissection to expose the aponeurosis and tarsus. Then, we placed the Putterman
      ptosis clamp to measure redundant aponeurotic and septal tissues and to perform
      the resection. Following the adjustment of the eyelid fissure, we refixed the
      levator muscle to the tarsus with 4-0 vicryl stitches. Results: Seventeen
      patients (34 eyes) were included in the study. Of the 34 eyes, 31 (91.2%)
      experienced the complete resolution of ptosis after the surgery. One patient (2
      eyes, 5.9%) had mild bilateral dermatochalasis and received revision surgery 6
      months postoperative. One patient (1 eye, 2.9%) lost the crease of the left eye
      and received revision surgeries 2 and 6 months after the first surgery. No
      residual ptosis or severe adverse events were noted in the patients. Conclusions:
      Modified levator muscle resection using the Putterman ptosis clamp is an
      effective procedure for ptosis treatment. Level of Evidence 4: 

PMID- 29194524
TI  - Functional sequencing read annotation for high precision microbiome analysis.
AB  - The vast majority of microorganisms on Earth reside in often-inseparable
      environment-specific communities-microbiomes. Meta-genomic/-transcriptomic
      sequencing could reveal the otherwise inaccessible functionality of microbiomes.
      However, existing analytical approaches focus on attributing sequencing reads to
      known genes/genomes, often failing to make maximal use of available data. We
      created faser (functional annotation of sequencing reads), an algorithm that is
      optimized to map reads to molecular functions encoded by the read-correspondent
      genes. The mi-faser microbiome analysis pipeline, combining faser with our
      manually curated reference database of protein functions, accurately annotates
      microbiome molecular functionality. mi-faser's minutes-per-microbiome processing
      speed is significantly faster than that of other methods, allowing for large
      scale comparisons. Microbiome function vectors can be compared between different
      conditions to highlight environment-specific and/or time-dependent changes in
      functionality. Here, we identified previously unseen oil degradation-specific
      functions in BP oil-spill data, as well as functional signatures of individual
      specific gut microbiome responses to a dietary intervention in children with
      Prader-Willi syndrome. Our method also revealed variability in Crohn's Disease
      patient microbiomes and clearly distinguished them from those of related healthy
      individuals. Our analysis highlighted the microbiome role in CD pathogenicity,
      demonstrating enrichment of patient microbiomes in functions that promote
      inflammation and that help bacteria survive it.

PMID- 29194525
TI  - Hematophagous Ectoparasites of Cliff Swallows Invade a Hospital and Feed on
      Humans.
AB  - We describe a hospital infestation by 2 hematophagous ectoparasites of cliff
      swallows that nested in the window eaves. Breaks in window seals allowed entry of
      swallow ticks and swallow bugs. These pests emerged in large numbers in patient
      rooms, hallways, and stairwells; 17% of the ticks fed on humans.

PMID- 29194529
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- 29194526
TI  - Bacterial Infections After Burn Injuries: Impact of Multidrug Resistance.
AB  - Patients who are admitted to the hospital after sustaining a large burn injury
      are at high risk for developing hospital-associated infections. If patients
      survive the initial 72 hours after a burn injury, infections are the most common
      cause of death. Ventilator-associated pneumonia is the most important infection
      in this patient population. The risk of infections caused by multidrug-resistant
      bacterial pathogens increases with hospital length of stay in burn patients. In
      the first days of the postburn hospitalization, more susceptible, Gram-positive
      organisms predominate, whereas later more resistant Gram-negative organisms are
      found. These findings impact the choice of empiric antibiotics in critically ill
      burn patients. A proactive infection control approach is essential in burn units.
      Furthermore, a multidisciplinary approach to burn patients with a team that
      includes an infectious disease specialist and a pharmacist in addition to the
      burn surgeon is highly recommended.

PMID- 29194530
TI  - A review of computational approaches for analysis of hepatitis C virus-mediated
      liver diseases.
AB  - Chronic infection of hepatitis C virus (HCV) leads to severe life-threatening
      liver diseases such as cirrhosis of liver, fibrosis and hepatocellular carcinoma
      (HCC). Severity of the disease infects >180 million people worldwide. In recent
      years, many computational approaches have been proposed to study and analyze the
      progression of liver fibrosis, HCC and other liver diseases developed from
      chronic HCV infection. In this article, we review the literature published in
      this area of study. Here we categorize all the approaches into two basic groups:
      analyzing gene expression and studying protein-protein interaction network among
      HCV-infected human proteins. We also review functional and pathway-enrichment
      analysis of HCV-interacted human proteins, which gives a clear understanding of
      functional perturbations leading to hepatocarcinogenesis. Topological analysis of
      HCV-human protein interaction network and HCV-HCC association network reveals
      important information of hepatocarcinogenesis progression in liver tissue. We
      compare the results of topological analysis performed in different studies.
      Moreover we observe that the HCV-interacted human proteins, which are also
      responsible for HCC progression, have relatively higher degree and betweenness
      centrality than that of the other HCV-interacted proteins.

PMID- 29194531
TI  - Conservative surgery versus colorectal resection in deep endometriosis
      infiltrating the rectum: a randomized trial.
AB  - STUDY QUESTION: Is there a difference in functional outcome between conservative
      versus radical rectal surgery in patients with large deep endometriosis
      infiltrating the rectum 2 years postoperatively? SUMMARY ANSWER: No evidence was
      found that functional outcomes differed when conservative surgery was compared to
      radical rectal surgery for deeply invasive endometriosis involving the bowel.
      WHAT IS KNOWN ALREADY: Adopting a conservative approach to the surgical
      management of deep endometriosis infiltrating the rectum, by employing shaving or
      disc excision, appears to yield improved digestive functional outcomes. However,
      previous comparative studies were not randomized, introducing a possible bias
      regarding the presumed superiority of conservative techniques due to the
      inclusion of patients with more severe deep endometriosis who underwent
      colorectal resection. STUDY DESIGN SIZE, DURATION: From March 2011 to August
      2013, we performed a 2-arm randomized trial, enroling 60 patients with deep
      endometriosis infiltrating the rectum up to 15 cm from the anus, measuring more
      than 20 mm in length, involving at least the muscular layer in depth and up to
      50% of rectal circumference. No women were lost to follow-up.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were enroled in three French
      university hospitals and had either conservative surgery, by shaving or disc
      excision, or radical rectal surgery, by segmental resection. Randomization was
      performed preoperatively using sequentially numbered, opaque, sealed envelopes,
      and patients were informed of the results of randomization. The primary endpoint
      was the proportion of patients experiencing one of the following symptoms:
      constipation (1 stool/>5 consecutive days), frequent bowel movements (>=3
      stools/day), defecation pain, anal incontinence, dysuria or bladder atony
      requiring self-catheterization 24 months postoperatively. Secondary endpoints
      were the values of the Visual Analog Scale (VAS), Knowles-Eccersley-Scott-Symptom
      Questionnaire (KESS), the Gastrointestinal Quality of Life Index (GIQLI), the
      Wexner scale, the Urinary Symptom Profile (USP) and the Short Form 36 Health
      Survey (SF36). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 60 patients were
      enroled. Among the 27 patients in the conservative surgery arm, two were
      converted to segmental resection (7.4%). In each group, 13 presented with at
      least one functional problem at 24 months after surgery (48.1 versus 39.4%, OR =
      0.70, 95% CI 0.22-2.21). The intention-to-treat comparison of the overall scores
      on KESS, GIQLI, Wexner, USP and SF36 did not reveal significant differences
      between the two arms. Segmental resection was associated with a significant risk
      of bowel stenosis. LIMITATIONS REASONS FOR CAUTION: The inclusion of only large
      infiltrations of the rectum does not allow the extrapolation of conclusions to
      small nodules of <20 mm in length. The presumption of a 40% difference favourable
      to conservative surgery in terms of postoperative functional outcomes resulted in
      a lack of power to demonstrate a difference for the primary endpoint. WIDER
      IMPLICATIONS OF THE FINDINGS: Conservative surgery is feasible in patients
      managed for large deep rectal endometriosis. The trial does not show a
      statistically significant superiority of conservative surgery for mid-term
      functional digestive and urinary outcomes in this specific population of women
      with large involvement of the rectum. There is a higher risk of rectal stenosis
      after segmental resection, requiring additional endoscopic or surgical
      procedures. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a
      grant from the clinical research programme for hospitals (PHRC) in France. The
      authors declare no competing interests related to this study. TRIAL REGISTRATION
      NUMBER: This study is registered with ClinicalTrials.gov, number NCT 01291576.
      TRIAL REGISTRATION DATE: 31 January 2011. DATE OF FIRST PATIENT'S ENROLMENT: 7
      March 2011.

PMID- 29194533
TI  - Corrigendum.

PMID- 29194532
TI  - Identification of more than 100 structurally unique DNA-phosphate adducts formed
      during rat lung carcinogenesis by the tobacco-specific nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone.
AB  - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) is a powerful lung carcinogen in animal models and is considered a
      causative factor for lung cancer in people who use tobacco products. NNK
      undergoes metabolic activation-a critical step in its mechanism of carcinogenesis
      to an intermediate which reacts with DNA to form pyridyloxobutyl DNA base and
      phosphate adducts. Another important metabolic pathway of NNK is its conversion
      to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which similarly forms
      pyridylhydroxybutyl DNA base adducts that have been characterized previously. In
      this study, we investigated the potential formation of pyridylhydroxybutyl DNA
      phosphate adducts. We report the characterization and quantitation of 107
      structurally unique pyridylhydroxybutyl DNA phosphate adducts in the lungs of
      rats treated chronically with a carcinogenic dose of 5 ppm of NNK in their
      drinking water for up to 70 weeks, by using a novel liquid chromatography
      nanoelectrospray ionization-high-resolution tandem mass spectrometry method. Our
      findings demonstrate that pyridylhydroxybutyl phosphate adducts account for 38-55
      and 34-40% of all the measured pyridine-containing DNA adducts in rat lung and
      liver, respectively, upon treatment with NNK. Some of the pyridylhydroxybutyl DNA
      phosphate adducts persisted in both tissues for over 70 weeks, suggesting that
      they could be potential biomarkers of chronic exposure to NNK and NNAL. This
      study provides comprehensive characterization and relative quantitation of a
      panel of NNK/NNAL-derived DNA phosphate adducts, thus identifying NNK as the
      source of the most structurally diverse set of DNA adducts identified to date
      from any carcinogen.

PMID- 29194534
TI  - Why not try harder? Computational approach to motivation deficits in neuro
      psychiatric diseases.
AB  - Motivation deficits, such as apathy, are pervasive in both neurological and
      psychiatric diseases. Even when they are not the core symptom, they reduce
      quality of life, compromise functional outcome and increase the burden for
      caregivers. They are currently assessed with clinical scales that do not give any
      mechanistic insight susceptible to guide therapeutic intervention. Here, we
      present another approach that consists of phenotyping the behaviour of patients
      in motivation tests, using computational models. These formal models impose a
      precise and operational definition of motivation that is embedded in decision
      theory. Motivation can be defined as the function that orients and activates the
      behaviour according to two attributes: a content (the goal) and a quantity (the
      goal value). Decision theory offers a way to quantify motivation, as the cost
      that patients would accept to endure in order to get the benefit of achieving
      their goal. We then review basic and clinical studies that have investigated the
      trade-off between the expected cost entailed by potential actions and the
      expected benefit associated with potential rewards. These studies have shown that
      the trade-off between effort and reward involves specific cortical, subcortical
      and neuromodulatory systems, such that it may be shifted in particular clinical
      conditions, and reinstated by appropriate treatments. Finally, we emphasize the
      promises of computational phenotyping for clinical purposes. Ideally, there would
      be a one-to-one mapping between specific neural components and distinct
      computational variables and processes of the decision model. Thus, fitting
      computational models to patients' behaviour would allow inferring of the
      dysfunctional mechanism in both cognitive terms (e.g. hyposensitivity to reward)
      and neural terms (e.g. lack of dopamine). This computational approach may
      therefore not only give insight into the motivation deficit but also help
      personalize treatment.

PMID- 29194535
TI  - Formation of Protein Disulfide Bonds Catalyzed by OsPDIL1;1 is Mediated by
      MicroRNA5144-3p in Rice.
AB  - Correct folding of proteins in the endoplasmic reticulum is important for their
      stability and function under stress. The protein disulfide isomerase (PDI)
      OsPDIL1;1 is a key protein-folding catalyst in rice (Oryza sativa L.). Here,
      microRNA5144 (osa-miR5144-3p) is reported to mediate the formation of protein
      disulfide bonds via targeting OsPDIL1;1 mRNA in rice seeds and seedlings during
      development and under conditions of abiotic stress, respectively. Expression
      analysis of transgenic rice and identification of cleavage sites showed that
      OsPDIL1;1 mRNA is a target of osa-miR5144-3p. Expression of osa-miR5144-3p and
      OsPDIL1;1 was shown to be inversely regulated in developing organs and under
      abiotic stress. The down-regulation of osa-miR5144-3p or overexpression of
      OsPDIL1;1 in transgenic rice showed increased total protein-disulfide bond
      content, compared with the wild type. This indicates that protein-disulfide bond
      formation is enhanced by down-regulation of osa-miR5144-3p or overexpression of
      OsPDIL1;1. These transgenic rice plants also displayed strong resistance to
      salinity and mercury stress, in comparison with the wild type. In contrast, the
      transgenic rice plants overexpressing osa-miR5144-3p or down-regulating OsPDIL1;1
      had a lower protein-disulfide bond content; they were susceptible to abiotic
      stress and produced abnormal grains with small and loosely packed starch
      granules. These results indicate that protein-disulfide bond formation catalyzed
      by OsPDIL1;1 is modulated by osa-miR5144-3p in rice during development and is
      involved in resistance to abiotic stress.

PMID- 29194537
TI  - Complex Effects of Superior Competitors and Resources on Culex restuans (Diptera:
      Culicidae) Oviposition.
AB  - A growing body of literature on mosquito oviposition behavior supports the
      hypothesis that females place eggs in habitats that provide best available
      opportunity for growth, development, and maturation of their offspring. We
      conducted a field experiment to evaluate Culex oviposition behavior in response
      to the interspecific competitor Aedes triseriatus (Say) (Diptera: Culicidae)
      larvae, and resources in the form of quantity of plant detritus, and dissolved
      nitrogen (TN) and phosphorus (TP) derived from that detritus. We tested a set of
      specific predictions: 1) As a poorer competitor, Culex will avoid ovipositing in
      containers with superior interspecific competitors; 2) Culex choose oviposition
      habitats that contain greater amount of resources for the microbial food of their
      offspring; 3) Sufficiently high resource abundance can override avoidance of
      oviposition in containers with interspecific competitors. Culex restuans Theobald
      (Diptera: Culicidae) was the only species ovipositing, and the oviposition
      responses changed over time. The effect of resources was more important in
      driving oviposition decisions at the beginning and end of the experiment. The
      amount of resources, as manifest by TN and TP concentrations, had differential
      effects on oviposition. At the beginning females laid more eggs in containers
      with low detritus, which had the highest TN. After that, females preferred those
      containers with high detritus, which had low TN and high TP. The effect of
      competitors was important only during the middle of the experiment.
      Paradoxically, even as a poorer competitor Cx. restuans preferentially oviposited
      in containers with late-instar Ae. triseriatus, suggesting that the presence of
      successful heterospecifics indicates a good quality larval habitat.

PMID- 29194536
TI  - circlncRNAnet: an integrated web-based resource for mapping functional networks
      of long or circular forms of noncoding RNAs.
AB  - Background: Despite their lack of protein-coding potential, long noncoding RNAs
      (lncRNAs) and circular RNAs (circRNAs) have emerged as key determinants in gene
      regulation, acting to fine-tune transcriptional and signaling output. These
      noncoding RNA transcripts are known to affect expression of messenger RNAs
      (mRNAs) via epigenetic and post-transcriptional regulation. Given their
      widespread target spectrum, as well as extensive modes of action, a complete
      understanding of their biological relevance will depend on integrative analyses
      of systems data at various levels. Findings: While a handful of publicly
      available databases have been reported, existing tools do not fully capture, from
      a network perspective, the functional implications of lncRNAs or circRNAs of
      interest. Through an integrated and streamlined design, circlncRNAnet aims to
      broaden the understanding of ncRNA candidates by testing in silico several
      hypotheses of ncRNA-based functions, on the basis of large-scale RNA-seq data.
      This web server is implemented with several features that represent advances in
      the bioinformatics of ncRNAs: (1) a flexible framework that accepts and processes
      user-defined next-generation sequencing-based expression data; (2) multiple
      analytic modules that assign and productively assess the regulatory networks of
      user-selected ncRNAs by cross-referencing extensively curated databases; (3) an
      all-purpose, information-rich workflow design that is tailored to all types of
      ncRNAs. Outputs on expression profiles, co-expression networks and pathways, and
      molecular interactomes, are dynamically and interactively displayed according to
      user-defined criteria. Conclusions: In short, users may apply circlncRNAnet to
      obtain, in real time, multiple lines of functionally relevant information on
      circRNAs/lncRNAs of their interest. In summary, circlncRNAnet provides a "one
      stop" resource for in-depth analyses of ncRNA biology. circlncRNAnet is freely
      available at http://app.cgu.edu.tw/circlnc/.

PMID- 29194539
TI  - A 10-year review of health care reform on Family Practice Integrated Care Project
      Taiwan experience.
AB  - Objective: Taiwan has launched a Family Practice Integrated Care Project (FPICP)
      to develop an accountable family doctor system since March 2003. We aim to report
      the effectiveness of this nationwide demonstration programme over a 10-year
      period. Methods: Papers and reports related to the FPICP published both in
      English and in Chinese from 2003 to 2015 were collected systematically based on
      keywords including 'family doctor', 'primary care', 'integrated care' and
      'Taiwan'. Also collected and reviewed were national health insurance
      administration annual reports and related publications from Taiwan Association of
      Family Medicine. Quality care indicators including structure, process and outcome
      for programme monitoring were reported. Results: Up to June 2015, the project had
      enrolled a total of 10.5% of Taiwan's population. Approximately 24.9% of primary
      care physicians and 29.7% of community clinics joined the project to serve the
      members of 426 community health care groups (CHCGs). Compared to non-members,
      CHCG members received more preventive care services, especially in adult health
      examination (49% versus 19%), Pap smear (29% versus 22%), elderly influenza
      vaccination (42% versus 28%) and immunochemical faecal occult blood test (43%
      versus 31%) (P < 0.01). Members showed a markedly high level of satisfaction
      (>95%), especially in overall satisfaction, provision of health consultation and
      information, and improvement in understanding personal health condition.
      Conclusions: In the future, through the support of family physicians and CHCGs, a
      person-centred integrated health care delivery system can be an effective
      solution to the current barriers in the medical care system.

PMID- 29194538
TI  - Mitochondrial abnormalities and disruption of the neuromuscular junction precede
      the clinical phenotype and motor neuron loss in hFUSWT transgenic mice.
AB  - FUS (fused in sarcoma) mislocalization and cytoplasmic aggregation are hallmark
      pathologies in FUS-related amyotrophic lateral sclerosis and frontotemporal
      dementia. Many of the mechanistic hypotheses have focused on a loss of nuclear
      function in the FUS-opathies, implicating dysregulated RNA transcription and
      splicing in driving neurodegeneration. Recent studies describe an additional
      somato-dendritic localization for FUS in the cerebral cortex implying a
      regulatory role in mRNA transport and local translation at the synapse. Here, we
      report that FUS is also abundant at the pre-synaptic terminal of the
      neuromuscular junction (NMJ), suggesting an important function for this protein
      at peripheral synapses. We have previously reported dose and age-dependent motor
      neuron degeneration in transgenic mice overexpressing human wild-type FUS,
      resulting in a motor phenotype detected by ~28 days and death by ~100 days. Now,
      we report the earliest structural events using electron microscopy and
      quantitative immunohistochemistry. Mitochondrial abnormalities in the pre
      synaptic motor nerve terminals are detected at postnatal day 6, which are more
      pronounced at P15 and accompanied by a loss of synaptic vesicles and
      synaptophysin protein coupled with NMJs of a smaller size at a time when there is
      no detectable motor neuron loss. These changes occur in the presence of abundant
      FUS and support a peripheral toxic gain of function. This appearance is typical
      of a 'dying-back' axonopathy, with the earliest manifestation being mitochondrial
      disruption. These findings support our hypothesis that FUS has an important
      function at the NMJ, and challenge the 'loss of nuclear function' hypothesis for
      disease pathogenesis in the FUS-opathies.

PMID- 29194540
TI  - How linked are national HIV and SRHR strategies? A review of SRHR and HIV
      strategies in 60 countries.
AB  - The connection between HIV and sexual and reproductive health and rights (SRHR)
      is widely recognised along with the benefits of linking them at the legal/policy,
      health systems, and service delivery levels. However, despite increased rhetoric
      about the need for this three-tiered approach, integrated service delivery has
      not been fully addressed at the legal/policy level through national strategies.
      Thus a review of HIV and SRHR strategies was conducted for 60 countries,
      determining the extent to which they reflected the intersections between HIV and
      SRHR. Each HIV strategy was scored on whether five key SRHR components were
      incorporated and had an associated measurable target. SRHR strategies were
      similarly assessed for incorporation of five HIV components and associated
      targets. HIV strategies had a higher level of inclusion of SRHR components with a
      global average of 6.6/10 compared to 3.7/10 for SRHR strategies. The highest
      scoring component was the elimination of mother-to-child transmission of HIV
      (EMTCT) and the lowest was SRHR of people living with HIV. Countries with higher
      scores in one strategy tended to have higher scores in the other but there was no
      difference over time. Whilst there has been increased global commitment since
      2004 to link SRHR and HIV, insufficient headway has been made in linking related
      national strategies. Although EMTCT is included with targets in the majority of
      HIV and SRHR strategies, the broader SRHR needs of women living with HIV are not.
      Also, condoms are not being considered an effective triple protection tool. HIV
      and SRHR strategies provide direction and targets which ultimately may influence
      funding and vice versa. Therefore, it is essential that these strategies are
      right-based and incorporate the key connections between SRHR and HIV with
      measurable targets to realise the full benefits of a joint response.

PMID- 29194541
TI  - Integrated care: learning between high-income, and low- and middle-income country
      health systems.
AB  - Over the past decade, discussion of integrated care has become more widespread
      and prominent in both high- and low-income health care systems (LMICs). The trend
      reflects the mismatch between an increasing burden of chronic disease and local
      health care systems which are still largely focused on hospital-based treatment
      of individual clinical episodes and also the long-standing proliferation of
      vertical donor-funded disease-specific programmes in LMICs which have disrupted
      horizontal, or integrated, care. Integration is a challenging concept to define,
      in part because of its multiple dimensions and varied scope: from integrated
      clinical care for individual patients to broader systems integration-or linkage
      involving a wide range of interconnected services (e.g. social services and
      health care). In this commentary, we compare integrated care in high- and lower
      income countries. Although contexts may differ significantly between these
      settings, there are many common features of how integration has been understood
      and common challenges in its implementation. We discuss the different approaches
      to, scope of, and impacts of, integration including barriers and facilitators to
      the processes of implementation. With the burden of disease becoming more alike
      across settings, we consider what gains there could be from comparative learning
      between these settings which have constituted two separate strands of research
      until now.

PMID- 29194542
TI  - Health systems and the SDGs: lessons from a joint HIV and sexual and reproductive
      health and rights response.

PMID- 29194543
TI  - Does service integration improve technical quality of care in low-resource
      settings? An evaluation of a model integrating HIV care into family planning
      services in Kenya.
AB  - The aim of this study was to investigate association between HIV and family
      planning integration and technical quality of care. The study focused on
      technical quality of client-provider consultation sessions. The cross-sectional
      study observed 366 client-provider consultation sessions and interviewed 37
      health care providers in 12 public health facilities in Kenya. Multilevel random
      intercept and linear regression models were fitted to the matched data to
      investigate relationships between service integration and technical quality of
      care as well as associations between facility-level structural and provider
      factors and technical quality of care. A sensitivity analysis was performed to
      test for hidden bias. After adjusting for facility-level structural factors,
      HIV/family planning integration was found to have significant positive effect on
      technical quality of the consultation session, with average treatment effect 0.44
      (95% CI: 0.63-0.82). Three of the 12 structural factors were significantly
      positively associated with technical quality of consultation session including:
      availability of family planning commodities (9.64; 95% CI: 5.07-14.21), adequate
      infrastructure (5.29; 95% CI: 2.89-7.69) and reagents (1.48; 95% CI: 1.02-1.93).
      Three of the nine provider factors were significantly positively associated with
      technical quality of consultation session: appropriate provider clinical
      knowledge (3.14; 95% CI: 1.92-4.36), job satisfaction (2.02; 95% CI: 1.21-2.83)
      and supervision (1.01; 95% CI: 0.35-1.68), while workload (-0.88; 95% CI: -1.75
      to - 0.01) was negatively associated. Technical quality of the client-provider
      consultation session was also determined by duration of the consultation and type
      of clinic visit and appeared to depend on whether the clinic visit occurred early
      or later in the week. Integration of HIV care into family planning services can
      improve the technical quality of client-provider consultation sessions as
      measured by both health facility structural and provider factors.

PMID- 29194545
TI  - Impact of integration of sexual and reproductive health services on consultation
      duration times: results from the Integra Initiative.
AB  - The lack of human resources is a key challenge in scaling up of HIV services in
      Africa's health care system. Integrating HIV services could potentially increase
      their effectiveness and optimize the use of limited resources and clinical staff
      time. We examined the impact of integration of provider initiated HIV counselling
      and testing (PITC) and family planning (FP counselling and FP provision) services
      on duration of consultation to assess the impact of PITC and FP integration on
      staff workload. This study was conducted in 24 health facilities in Kenya under
      the Integra Initiative, a non-randomized, pre/post intervention trial to evaluate
      the impact of integrated HIV and sexual and reproductive health services on
      health and service outcomes. We compared the time spent providing PITC-only
      services, FP-only services and integrated PITC/FP services. We used log-linear
      regression to assess the impact of plausible determinants on the duration of
      clients' consultation times. Median consultation duration times were highest for
      PITC-only services (30 min), followed by integrated services (10 min) and FP-only
      services (8 min). Times for PITC-only and FP-only services were 69.7% higher (95%
      Confidence Intervals (CIs) 35.8-112.0) and 43.9% lower (95% CIs -55.4 to - 29.6)
      than times spent on these services when delivered as an integrated service,
      respectively. The reduction in consultation times with integration suggests a
      potential reduction in workload. The higher consultation time for PITC-only could
      be because more pre- and post-counselling is provided at these stand-alone
      services. In integrated PITC/FP services, the duration of the visit fell below
      that required by HIV testing guidelines, and service mix between counselling and
      testing substantially changed. Integration of HIV with FP services may compromise
      the quality of services delivered and care must be taken to clearly specify and
      monitor appropriate consultation duration times and procedures during the process
      of integrating HIV and FP services.

PMID- 29194544
TI  - Numbers, systems, people: how interactions influence integration. Insights from
      case studies of HIV and reproductive health services delivery in Kenya.
AB  - Drawing on rich data from the Integra evaluation of integrated HIV and
      reproductive-health services, we explored the interaction of systems hardware and
      software factors to explain why some facilities were able to implement and
      sustain integrated service delivery while others were not. This article draws on
      detailed mixed-methods data for four case-study facilities offering reproductive
      health and HIV services between 2009 and 2013 in Kenya: (i) time-series client
      flow, tracking service uptake for 8841 clients; (ii) structured questionnaires
      with 24 providers; (iii) in-depth interviews with 17 providers; (iv) workload and
      facility data using a periodic activity review and cost-instruments; and (v)
      contextual data on external activities related to integration in study sites.
      Overall, our findings suggested that although structural factors like stock-outs,
      distribution of staffing and workload, rotation of staff can affect how
      integrated care is provided, all these factors can be influenced by staff
      themselves: both frontline and management. Facilities where staff displayed
      agency of decision making, worked as a team to share workload and had management
      that supported this, showed better integration delivery and staff were able to
      overcome some structural deficiencies to enable integrated care. Poor-performing
      facilities had good structural integration, but staff were unable to utilize this
      because they were poorly organized, unsupported or teams were dysfunctional.
      Conscientious objection and moralistic attitudes were also barriers.Integra has
      demonstrated that structural integration is not sufficient for integrated service
      delivery. Rather, our case studies show that in some cases excellent leadership
      and peer-teamwork enabled facilities to perform well despite resource shortages.
      The ability to provide support for staff to work flexibly to deliver integrated
      services and build resilient health systems to meet changing needs is
      particularly relevant as health systems face challenges of changing burdens of
      disease, climate change, epidemic outbreaks and more.

PMID- 29194546
TI  - Building integrated health systems: lessons from HIV, sexual and reproductive
      health integration.

PMID- 29194548
TI  - DETERMINATION OF THE BACKGROUND OF 3He-FILLED PROPORTIONAL COUNTERS USED FOR LOW
      LEVEL NEUTRON MEASUREMENTS.
AB  - Low-level neutron measurements are required for applications such as
      environmental monitoring, measurements of weak sources and the determination of
      neutron fluxes at underground laboratories. When analyzing low-level neutron
      measurements, it is important to be able to distinguish the signal due to
      neutrons from any background term that may originate within the detector. A
      solution to this problem has been developed for the case of measurements carried
      out with 3He spherical proportional counters of the type which are often used in
      Bonner sphere spectrometers. To determine this background, measurements were
      carried out in the former UDO underground laboratory of the Physikalisch
      Technische Bundesanstalt located in the Asse salt mine. The analysis of the data
      was carried out using Bayesian parameter estimation. The result of the analysis
      is a very general parameterised function that can be used to describe the pulse
      height spectrum due to the background of the proportional counters.

PMID- 29194547
TI  - Neutralizing Antibody Correlates Analysis of Tetravalent Dengue Vaccine Efficacy
      Trials in Asia and Latin America.
AB  - Background: In the CYD14 and CYD15 Phase 3 trials of the CYD-TDV dengue vaccine,
      estimated vaccine efficacy (VE) against symptomatic, virologically confirmed
      dengue (VCD) occurring between months 13 and 25 was 56.5% and 60.8%,
      respectively. Methods: Neutralizing antibody titers to the 4 dengue serotypes in
      the CYD-TDV vaccine insert were measured at month 13 in a randomly sampled
      immunogenicity subcohort and in all VCD cases through month 25 (2848 vaccine,
      1574 placebo) and studied for their association with VCD and with the level of VE
      to prevent VCD. Results: For each trial and serotype, vaccinees with higher month
      13 titer to the serotype had significantly lower risk of VCD with that serotype
      (hazard ratios, 0.19-0.43 per 10-fold increase). Moreover, for each trial,
      vaccinees with higher month 13 average titer to the 4 serotypes had significantly
      higher VE against VCD of any serotype (P < .001). Conclusions: Neutralizing
      antibody titers postdose 3 correlate with CYD-TDV VE to prevent dengue. High
      titers associate with high VE for all serotypes, baseline serostatus groups, age
      groups, and both trials. However, lowest titers do not fully correspond to zero
      VE, indicating that other factors influence VE.

PMID- 29194549
TI  - Stability of Synthetic Cathinones in Urine.
AB  - In this report, we evaluate the concentration, pH, temperature and analyte
      dependent effects on cathinone stability in preserved human urine. A total of 22
      synthetic cathinones were evaluated at 100 ng/mL and 1,000 ng/mL in pH 4 and pH 8
      urine over 6 months. Specimens were stored at -20 degrees C, 4 degrees C, 20
      degrees C and 32 degrees C. The stability of synthetic cathinones was highly
      dependent on urine pH and storage temperature. Cathinones were considerably more
      stable in acidic urine (pH 4) at low temperature. In alkaline urine (pH 8) at 32
      degrees C, significant losses (>20%) were observed within hours for the majority
      of drugs. In contrast, all drugs were stable in frozen and refrigerated urine at
      pH 4 for the duration of the study. These results highlight the importance of
      sample storage and the potential for pre-analytical changes in concentration
      during routine shipping and handling of specimens. Significant structural
      influence was also observed. Cathinones bearing a tertiary amine (pyrrolidine
      group) were significantly more stable than their secondary amine counterparts.
      The methylenedioxy group also exerted a significant stabilizing effect on both
      the tertiary and secondary amines. In the absence of the methylenedioxy group, no
      significant differences in stability were observed between the unsubstituted and
      ring substituted secondary amines. Half-lives at ambient temperature in pH 8
      urine ranged from 9 h (3-fluoromethcathinone) to 4.3 months
      (methylenedioxypyrovalerone and 3,4-methylenedioxy-alpha
      pyrrolidinobutiophenone), demonstrating the importance of analyte dependence, and
      the dual stabilizing effect of both the pyrollidine and methylenedioxy groups.
      Biological evidence may be subjected to a variety of environmental conditions
      prior to, and during transport to the forensic laboratory. These findings
      demonstrate the inherent instability of certain cathinone species in biological
      evidence under some conditions. Moreover, this study highlights the need for
      quantitative drug findings in toxicological investigations to be interpreted
      cautiously, and within the context of specimen storage and integrity.

PMID- 29194550
TI  - Comment on: Patients' preferences for anti-osteoporosis drug treatment: a cross
      European discrete choice experiment.

PMID- 29194551
TI  - Bypassing bacterial infection in phage display by sequencing DNA released from
      phage particles.
AB  - Phage display relies on a bacterial infection step in which the phage particles
      are replicated to perform multiple affinity selection rounds and to enable the
      identification of isolated clones by DNA sequencing. While this process is
      efficient for wild-type phage, the bacterial infection rate of phage with mutant
      or chemically modified coat proteins can be low. For example, a phage mutant with
      a disulfide-free p3 coat protein, used for the selection of bicyclic peptides,
      has a more than 100-fold reduced infection rate compared to the wild-type. A
      potential strategy for bypassing the bacterial infection step is to directly
      sequence DNA extracted from phage particles after a single round of phage panning
      using high-throughput sequencing. In this work, we have quantified the fraction
      of phage clones that can be identified by directly sequencing DNA from phage
      particles. The results show that the DNA of essentially all of the phage
      particles can be 'decoded', and that the sequence coverage for mutants equals
      that of amplified DNA extracted from cells infected with wild-type phage. This
      procedure is particularly attractive for selections with phage that have a
      compromised infection capacity, and it may allow phage display to be performed
      with particles that are not infective at all.

PMID- 29194553
TI  - Clinical signs in hypothyroidism-myoedema and Woltman sign.

PMID- 29194552
TI  - Structural basis of DNA duplex distortion induced by thiazole-containing hairpin
      polyamides.
AB  - This manuscript reports the molecular basis for double-stranded DNA (dsDNA)
      binding of hairpin polyamides incorporating a 5-alkyl thiazole (Nt) unit. Hairpin
      polyamides containing an N-terminal Nt unit induce higher melting stabilisation
      of target dsDNA sequences relative to an archetypical hairpin polyamide
      incorporating an N-terminal imidazole (Im) unit. However, modification of the N
      terminus from Im to Nt-building blocks results in an increase in dsDNA binding
      affinity but lower G-selectivity. A general G-selectivity trend is observed for
      Nt-containing polyamide analogues. G-selectivity increases as the steric bulk in
      the Nt 5-position increases. Solution-based NMR structural studies reveal
      differences in the modulation of the target DNA duplex of Nt-containing hairpin
      polyamides relative to the Im-containing archetype. A structural hallmark of an
      Nt polyamide*dsDNA complex is a more significant degree of major groove
      compression of the target dsDNA sequence relative to the Im-containing hairpin
      polyamide.

PMID- 29194554
TI  - "Grapes" by Deena Sackman.

PMID- 29194555
TI  - Three Simple Mindfulness Practices to Manage Holiday Stress.

PMID- 29194556
TI  - FDA-Approved Drugs to Treat Schizophrenia.

PMID- 29194557
TI  - Caution is Key When Prescribing for Older Adults.
AB  - The end of the year can trigger the recognition that aging adults are no longer
      as independent as they once were. Psychiatric nurses and other mental health
      professionals may see an increase in older adults being referred for treatment.
      As the most appropriate psychosocial/psychotherapeutic and psychopharmacological
      treatments are identified for older adults, there are some unique challenges
      inherent in coordinating the care of this population. It is especially important
      for prescribing psychiatric advanced practice nurses to update, review, and cross
      reference older patients' lists of medications at every appointment. Although the
      obstacles to treating older adults may appear daunting, prudent, responsible,
      cautious practice should be exercised to ensure they achieve improved
      functionality, maintain safety, reduce risks, and enhance their quality of life.
      [Journal of Psychosocial Nursing and Mental Health Services, 55(12), 7-10.].

PMID- 29194558
TI  - Nurses With Substance Use Disorders: Where We Are and What Needs To Be Done.
AB  - Nurses have the same rate of substance use disorders (SUDs) as the general
      public. Management of nurses with SUDs is moving from being punitive, including
      public license suspension or revocation, to alternative-to-discipline (ATD)
      programs that focus on early intervention and non-punitive, confidential help,
      which often involve continued employment. These programs have good retention
      rates, and nurses who complete them have fewer criminal convictions and are able
      to retain their nursing licenses and maintain successful careers in nursing.
      Barriers to nurses receiving care for SUDs include wide variability in ATD
      programs, inconsistent funding for treatment, and lack of policies and support
      for nursing students. Recommendations include changes to nurse practice acts to
      make ATD programs more uniform, provide adequate funding for all nurses and
      nursing students, and allow nurses to seek and obtain care without disclosing
      directly to Boards of Nurses. Colleges of nursing should implement policies to
      encourage early identification and treatment in nursing students, including ATD
      and dismissal programs. [Journal of Psychosocial Nursing and Mental Health
      Services, 55(12), 11-14.].

PMID- 29194559
TI  - The limits of the decentred state: the case of policing insurance claims fraud.
AB  - Existing research clearly shows that the public-private divide is continuously
      being challenged, recast and transformed. However, this article argues that a
      sharp distinction between public and private continues to operate as an important
      norm for professionals involved in the investigation of insurance claims fraud in
      Sweden. It shows how power within private insurance companies and the police
      authority is organized around the public-private divide, which is in turn
      mobilized to justify repression and to give investigations legitimacy. The
      article indicates that the formal public-private distinction is far more
      thoroughly maintained than is suggested by the existing literature. Rather than
      challenging the centrality of state power, private insurers and the police
      construct, maintain and have a stake in the reproduction of a state-centric
      monopoly of crime control.

PMID- 29194560
TI  - Individualized treatment approaches for Langerhans cell histiocytosis.

PMID- 29194561
TI  - Gestational diabetes in primiparous women-impact of age and adiposity: a register
      based cohort study.
AB  - INTRODUCTION: Data on risk factors for gestational diabetes mellitus (GDM) in
      primiparous women is limited. The aim of this study was to assess the prevalence
      of GDM and simultaneously evaluate the impact of age and adiposity in primiparous
      women at risk of GDM risk. MATERIAL AND METHODS: This observational register
      based cohort study from the city of Vantaa, Finland, included all 7750
      primiparous women giving birth between 2009 and 2015 without previously diagnosed
      diabetes mellitus. RESULTS: In primiparous women the prevalence of GDM was 16.5%
      and mean age was 28.2 years (5.2 SD). Primiparous women aged >=35 years had a
      significantly higher risk for GDM than women aged <25 years [odds ratio (OR)
      2.67, 95% confidence interval (CI) 2.13-3.34]. Primiparous women with a pre
      pregnancy body mass index (BMI) >=30.0 kg/m2 had a significantly higher risk for
      GDM than women with a pre-pregnancy BMI <25 kg/m2 (OR 5.36, 95% CI 4.53-6.36).
      The risk of developing GDM showed an increasing trend with increasing age in all
      BMI categories except the category BMI >=35 kg/m2 . Normal weight women (BMI 20.0
      24.9 kg/m2 ) aged 40 years had a significantly higher risk for GDM than normal
      weight women aged 28 years (OR 1.48, 95% CI 1.01-2.19). CONCLUSIONS: The
      prevalence of GDM is high in primiparous women. Both age and degree of adiposity
      influenced the risk for GDM. To reduce GDM risk, adiposity should be prevented
      already in childhood and primiparity should be encouraged at a younger age.

PMID- 29194562
TI  - A risk score including microdeletions improves relapse prediction for standard
      and medium risk precursor B-cell acute lymphoblastic leukaemia in children.
AB  - To prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is
      treated very intensively. However, most patients who eventually relapse have
      standard or medium risk ALL with low minimal residual disease (MRD) levels. We
      analysed recurrent microdeletions and other clinical prognostic factors in a
      cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with
      the aim of better predicting relapse and refining risk stratification. Lower
      relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic
      deletions (P < 0.0001); P2RY8-CRLF2 gene fusion (P < 0.0004); Day 33 MRD>5 * 10-5
      (P < 0.0001) and High National Cancer Institute (NCI) risk (P < 0.0001). We
      created a predictive model based on a risk score (RS) for deletions, MRD and NCI
      risk, extending from an RS of 0 (RS0) for patients with no unfavourable factors
      to RS2 +  for patients with 2 or 3 high risk factors. RS0, RS1, and RS2 +  groups
      had RFS of 93%, 78% and 49%, respectively, and overall survival (OS) of 99%, 91%
      and 71%. The RS provided greater discrimination than MRD-based risk
      stratification into standard (89% RFS, 96% OS) and medium risk groups (79% RFS,
      91% OS). We conclude that this RS may enable better early therapeutic
      stratification and thus improve cure rates for childhood ALL.

PMID- 29194563
TI  - Cyclic analogues of alpha-conotoxin Vc1.1 inhibit colonic nociceptors and provide
      analgesia in a mouse model of chronic abdominal pain.
AB  - BACKGROUND AND PURPOSE: Patients with irritable bowel syndrome suffer from
      chronic visceral pain (CVP) and limited analgesic therapeutic options are
      currently available. We have shown that alpha-conotoxin Vc1.1 induced activation
      of GABAB receptors on the peripheral endings of colonic afferents and reduced
      nociceptive signalling from the viscera. However, the analgesic efficacy of more
      stable, cyclized versions of Vc1.1 on CVP remains to be determined. EXPERIMENTAL
      APPROACH: Using ex vivo colonic afferent preparations from mice, we determined
      the inhibitory actions of cyclized Vc1.1 (cVc1.1) and two cVc1.1 analogues on
      mouse colonic nociceptors in healthy and chronic visceral hypersensitivity (CVH)
      states. Using whole-cell patch clamp recordings, we also assessed the inhibitory
      actions of these peptides on the neuronal excitability of colonic innervating
      dorsal root ganglion neurons. In vivo, the analgesic efficacy of these analogues
      was assessed by determining the visceromotor response to colorectal distension in
      healthy and CVH mice. KEY RESULTS: cVc1.1 and the cVc1.1 analogues,
      [C2H,C8F]cVc1.1 and [N9W]cVc1.1, all caused concentration-dependent inhibition of
      colonic nociceptors from healthy mice. Inhibition by these peptides was greater
      than those evoked by linear Vc1.1 and was substantially greater in colonic
      nociceptors from CVH mice. cVc1.1 also reduced excitability of colonic dorsal
      root ganglion neurons, with greater effect in CVH neurons. CVH mice treated with
      cVc1.1 intra-colonically displayed reduced pain responses to noxious colorectal
      distension compared with vehicle-treated CVH mice. CONCLUSIONS AND IMPLICATIONS:
      Cyclic versions of Vc1.1 evoked significant anti-nociceptive actions in CVH
      states, suggesting that they could be novel candidates for treatment of CVP.
      LINKED ARTICLES: This article is part of a themed section on Recent Advances in
      Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this
      section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

PMID- 29194565
TI  - Impaired Langerhans cell migration in psoriasis is due to an altered keratinocyte
      phenotype induced by interleukin-17.
AB  - BACKGROUND: Psoriasis is a common skin condition driven by increased expression
      of interleukin (IL)-17. Langerhans cells (LCs) are epidermal dendritic cells that
      regulate cutaneous immune responses. Within the uninvolved skin of patients with
      psoriasis, LCs display impaired migration from the epidermis. OBJECTIVES: To
      investigate the role of keratinocytes (KCs) in the regulation of LC function and
      the response of KCs to IL-17. METHODS: KCs were cultured from the uninvolved skin
      of patients with psoriasis and healthy individuals with or without IL-17
      treatment and the conditioned medium examined for its ability to alter LC
      function in an ex vivo human skin explant model. Furthermore, we examined the
      effect of IL-17 on LC mobilization in psoriasis by neutralizing IL-17 in the same
      skin explant model. RESULTS: Conditioned medium from psoriasis KCs inhibited LC
      migration in healthy skin. Moreover, conditioned medium from healthy KCs treated
      with IL-17 also inhibited healthy LC migration. Finally, neutralizing IL-17 in
      psoriasis skin resulted in enhanced LC migration. CONCLUSIONS: Collectively,
      these data suggest that an altered KC secretome, driven by increased expression
      of IL-17, is responsible for impaired LC migration in the uninvolved skin of
      patients with psoriasis.

PMID- 29194567
TI  - Low vs high haemoglobin trigger for transfusion in vascular surgery: protocol for
      a randomised trial.

PMID- 29194566
TI  - National screening guidelines and developments in prenatal diagnoses and live
      births of Down syndrome in 1973-2016 in Denmark.
AB  - INTRODUCTION: Denmark was the first country in the world to implement a national,
      free-for-all offer of prenatal screening for Down syndrome to all pregnant women.
      It has a high uptake (>90%) compared to other countries. Thus, Denmark offers an
      interesting case for investigating the consequences of implementing
      comprehensive, national prenatal screening guidelines. The aim of this study was
      to describe the historical developments in invasive procedures, pre-/postnatal
      diagnoses of Down syndrome and Down syndrome live births in the period 1973-2016
      in Denmark. MATERIAL AND METHODS: Data on invasive procedures, pre- and postnatal
      Down syndrome diagnoses were retrieved from the Danish Cytogenetic Central
      Registry. RESULTS: From 1973 to 1993, screening based on maternal age and high
      risk indications resulted in a constant increase in invasive procedures. After
      the introduction of the triple test in 1994, invasive procedures decreased for
      the first time in 20 years. Following the introduction of an offer of combined
      screening to all pregnant women in 2004, the number of invasive procedures
      decreased markedly, while there was a concurrent increase in prenatal diagnoses
      of Down syndrome. Additionally, the number of Down syndrome live births decreased
      suddenly and significantly, but subsequently stabilized at 23-35 annual live
      births. Of these, the majority were diagnosed postnatally. CONCLUSION: Though
      prenatal screening technologies constantly improve, it was the introduction of
      and adherence to national guidelines that resulted in marked shifts in screening
      procedures and outcome in Denmark.

PMID- 29194568
TI  - Clarification of methodology and further results from the pivotal phase 3 study
      of crisaborole for mild-moderate atopic dermatitis.

PMID- 29194564
TI  - Oxaliplatin-induced enteric neuronal loss and intestinal dysfunction is prevented
      by co-treatment with BGP-15.
AB  - BACKGROUND AND PURPOSE: Gastrointestinal side effects of chemotherapy are an
      under-recognized clinical problem, leading to dose reduction, delays and
      cessation of treatment, presenting a constant challenge for efficient and
      tolerated anti-cancer treatment. We have found that oxaliplatin treatment results
      in intestinal dysfunction, oxidative stress and loss of enteric neurons. BGP-15
      is a novel cytoprotective compound with potential HSP72 co-inducing and PARP
      inhibiting properties. In this study, we investigated the potential of BGP-15 to
      alleviate oxaliplatin-induced enteric neuropathy and intestinal dysfunction.
      EXPERIMENTAL APPROACH: Balb/c mice received oxaliplatin (3 mg.kg-1 .day-1 ) with
      and without BGP-15 (15 mg.kg-1 .day-1 : i.p.) tri-weekly for 14 days.
      Gastrointestinal transit was analysed via in vivo X-ray imaging, before and after
      treatment. Colons were collected to assess ex vivo motility, neuronal
      mitochondrial superoxide and cytochrome c levels and for immunohistochemical
      analysis of myenteric neurons. KEY RESULTS: Oxaliplatin-induced neuronal loss
      increased the proportion of neuronal NO synthase-immunoreactive neurons and
      increased levels of mitochondrial superoxide and cytochrome c in the myenteric
      plexus. These changes were correlated with an increase in PARP-2 immunoreactivity
      in the colonic mucosa and were attenuated by BGP-15 co-treatment. Significant
      delays in gastrointestinal transit, intestinal emptying and pellet formation,
      impaired colonic motor activity, reduced faecal water content and lack of weight
      gain associated with oxaliplatin treatment were restored to sham levels in mice
      co-treated with BGP-15. CONCLUSION AND IMPLICATIONS: Our results showed that BGP
      15 ameliorated oxidative stress, increased enteric neuronal survival and
      alleviated oxaliplatin-induced intestinal dysfunction, suggesting that BGP-15 may
      relieve the gastrointestinal side effects of chemotherapy.

PMID- 29194569
TI  - Cohort studies in the context of obstetric and gynecologic research: a
      methodologic overview.
AB  - Observational cohort studies represent one of the most powerful designs in
      epidemiology. They are also the basis of evidence in many areas of obstetric and
      gynecologic research, given that randomization of women, couples or pregnancies
      is often impossible or unethical. Indeed, well-conceived cohort studies have led
      to a better understanding of many important clinical and public health questions
      over time, including the impact of different exposures on perinatal and pediatric
      outcomes in pregnant women and their children. In this paper, we describe the
      main features, challenges, and limitations of cohort studies in the context of
      obstetric and gynecologic research. As with all epidemiologic studies, cohort
      studies present numerous challenges and are vulnerable to bias. However, as we
      describe throughout this review, careful design - from formulating the study
      question to planning statistical analysis - can reduce the potential for bias.
      When possible, we also provide examples from the gynecological and obstetrical
      literature to illustrate the epidemiological challenge and suggest specific
      readings.

PMID- 29194570
TI  - Characterization of CD45RO+ memory T lymphocytes in keloid disease.
AB  - BACKGROUND: Memory T cells, a highly effective subset of T lymphocytes, have been
      reported to be involved in many inflammatory skin disorders. However, the
      potential role of memory T cells in keloid disease (KD) remains unclear.
      OBJECTIVES: Due to their important role in regulating inflammation, we
      investigated the characteristics of CD45RO+ memory T cells in KD. METHODS:
      Primary cutaneous cells were isolated from keloid scars and normal skin by
      enzymic digestion. Peripheral blood mononuclear cells were isolated from a
      related blood sample, and flow cytometry was applied to identify the phenotypic
      and functional abnormalities of memory T cells in KD. RESULTS: We observed that
      the majority of T lymphocytes in keloid scars had the memory phenotype, and a
      greater number of the CD8+ memory T cells in keloid scars produced lower levels
      of tumour necrosis factor (TNF)-alpha. This abnormal cytokine production was even
      more distinct in Forkhead box (FOX)P3-  CD8- memory T cells, with lower TNF-alpha
      production and enhanced interferon-gamma production. Furthermore, FOXP3+  CD8-
      memory T cells in keloid scars were abnormal, including showing reduced CD25 and
      cytotoxic T-lymphocyte-associated antigen 4 expression and interleukin-10
      production. In addition, a significant decrease in the number of CD4+  CD25high 
      FOXP3+ regulatory T cells was identified in patients with multiple keloid scars.
      We also found that there was significantly increased infiltration of CD103+  CD8+
      memory T cells in keloid scars. CONCLUSIONS: Our findings preliminarily elucidate
      the abnormalities of CD45RO+ memory T cells in keloid scars and provide early
      evidence that a disrupted T-cell response contributes to the progression of KD.

PMID- 29194571
TI  - The transfusion trigger in major surgery.

PMID- 29194572
TI  - IgG response against Staphylococcus aureus is associated with severe atopic
      dermatitis in children.
AB  - BACKGROUND: An altered immune response against Staphylococcus aureus might
      contribute to inflammation and barrier damage in atopic dermatitis (AD).
      OBJECTIVES: To profile IgG antibodies against 55 S. aureus antigens in sera of
      children with mild-to-severe AD and to evaluate the association between IgG
      levels and disease severity. METHODS: In this cross-sectional study, we included
      children with AD from two interventional study cohorts, the Shared Medical
      Appointment (SMA) cohort (n = 131) and the older DAVOS cohort (n = 76). AD
      severity was assessed using the Self-Administered Eczema Area and Severity Index
      (SA-EASI) and levels of thymus and activation-regulated chemokine (TARC) in
      serum. IgG antibody levels against 55 S. aureus antigens were quantified
      simultaneously using a Luminex assay. Pair-wise correlations were calculated
      between the 55 IgG levels using the Spearman rank correlation test. Linear
      regression analysis was performed to test for associations between 55 IgG levels
      and SA-EASI and TARC, adjusting for age, sex and S. aureus colonization. RESULTS:
      In the SMA cohort, 16 antigens were associated with SA-EASI and 12 with TARC (10
      overlapping antigens; P-values 0.001-0.044). The associated IgG antibodies
      targeted mainly secreted proteins with immunomodulatory functions. In the DAVOS
      study, IgG levels against only four and one S. aureus antigen(s) were associated
      with SA-EASI and TARC, respectively (no overlap). CONCLUSIONS: In young children,
      severity of AD is associated with an IgG response directed against S. aureus
      antigens with mainly immunomodulatory functions. These findings encourage further
      evaluation of the role of S. aureus in the pathogenesis of AD.

PMID- 29194573
TI  - Stability and Change in Cognitive Status Classification of Black Older Adults.
AB  - OBJECTIVES: The purpose of this study was to determine whether stability and
      change in cognitive status are associated with sociodemographic characteristics
      and health function. DESIGN: Secondary analysis of data. SETTING: Baltimore Study
      of Black Aging-Patterns of Cognitive Aging. PARTICIPANTS: Community-dwelling
      black adults (N = 407; mean age 68.6 +/- 9.1). MEASUREMENTS: Baseline (n = 602)
      and 33-month follow-up (n = 450) assessments of cognition, health, and
      psychosocial function. RESULTS: For the present analyses, participants were
      grouped as being cognitively normal (n = 249), having stable mild cognitive
      impairment (MCI) (n = 32), or being MCI converters (n = 72; normal at baseline,
      MCI at follow-up) or reverters (n = 54; MCI at baseline, normal at follow-up).
      Multivariate analysis of variance showed that the groups differed significantly
      in education and lung function (P < .010). Post hoc analyses indicated that
      converters had fewer years of education than the other groups, whereas those who
      were cognitively normal had better lung function than converters and reverters (P
      < .050). CONCLUSION: These results suggest that education and lung health are
      associated with patterns of cognitive status change and stability. Future
      research should account for sociodemographic and health factors when examining
      stability of cognitive status classifications.

PMID- 29194574
TI  - Opioid use among cancer survivors: A call to action for oncology and primary care
      providers.

PMID- 29194575
TI  - The adjuvant system AS01 up-regulates neutrophil CD14 expression and neutrophil
      associated antigen transport in the local lymphatic network.
AB  - The liposome-based adjuvant system AS01 is under evaluation for use in several
      vaccines in clinical development. We have shown previously that AS01 injected
      with hepatitis B surface antigen (HBsAg) induces a distinct cellular signature
      within the draining lymphatics that enhances local lymphocyte recruitment and
      antigen-specific humoral immunity. Here, we show that AS01-induced neutrophil
      recruitment is associated with increased expression of CD14 and enhanced antigen
      uptake capacity in neutrophils from both afferent and efferent lymphatic
      compartments during the first 48 h after vaccination. Significant and transient
      increases in CD14 expression on systemic neutrophils were also observed following
      primary and boost vaccination with HBsAg-AS01; however, they were not observed
      following additional encounter with HBsAg-alone or HBsAg-alum. These results show
      that following immunization with AS01, neutrophils expressing higher levels of
      CD14 are both more abundant and efficient at antigen uptake, warranting further
      investigation into the role of neutrophil-associated CD14 in the adjuvanticity of
      AS01.

PMID- 29194576
TI  - NMR analysis of the backbone dynamics of the small GTPase Rheb and its
      interaction with the regulatory protein FKBP38.
AB  - Ras homolog enriched in brain (Rheb) is a small GTPase that regulates
      mammalian/mechanistic target of rapamycin complex 1 (mTORC1) and, thereby, cell
      growth and metabolism. Here we show that cycling between the inactive GDP- and
      the active GTP-bound state modulates the backbone dynamics of a C-terminal
      truncated form, RhebDeltaCT, which is suggested to influence its interactions. We
      further investigated the interactions between RhebDeltaCT and the proposed Rheb
      binding domain of the regulatory protein FKBP38. The observed weak interactions
      with the GTP-analogue- (GppNHp-) but not the GDP-bound state, appear to
      accelerate the GDP to GTP exchange, but only very weakly compared to a genuine
      GEF. Thus, FKBP38 is most likely not a GEF but a Rheb effector that may function
      in membrane targeting of Rheb.

PMID- 29194577
TI  - Cerebral cortex development: an outside-in perspective.
AB  - The cerebral cortex is a complex structure that contains different classes of
      neurons distributed within six layers and regionally organized into highly
      specialized areas. Cortical layering arises during embryonic development in an
      inside-out manner as forebrain progenitors proliferate and generate distinct
      waves of interneurons and projection neurons. Radial glial cells (RGCs) derive
      from neuroepithelial cells and are the founding cortical progenitors. At the
      onset of corticogenesis, RGCs expand their pool by proliferative divisions. As
      corticogenesis proceeds, they gradually undergo differentiative divisions to
      either generate neurons directly (direct neurogenesis) or indirectly via
      production of intermediate progenitors that further divide to generate pairs of
      neurons (indirect neurogenesis). The fate of RGCs is finely regulated during all
      the corticogenesis process and depends on time-scaled perception of external
      signals and expression of intrinsic factors. The present Review focuses on the
      role of physiological extracellular cues arising from the vicinity of neural
      progenitors on the regulation of dorsal neurogenesis and cerebral cortex
      patterning. It further discusses how pathogenic viral factors influence RGC
      behaviour and disrupt cerebral cortex development.

PMID- 29194578
TI  - Long-term effects of corpus callosotomy for therapy-resistant epileptic seizures.

PMID- 29194579
TI  - Targeted gene sequencing and whole-exome sequencing in autopsied fetuses with
      prenatally diagnosed kidney anomalies.
AB  - Identification of fetal kidney anomalies invites questions about underlying
      causes and recurrence risk in future pregnancies. We therefore investigated the
      diagnostic yield of next-generation sequencing in fetuses with bilateral kidney
      anomalies and the correlation between disrupted genes and fetal phenotypes.
      Fetuses with bilateral kidney anomalies were screened using an in-house-designed
      kidney-gene panel. In families where candidate variants were not identified,
      whole-exome sequencing was performed. Genes uncovered by this analysis were added
      to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%)
      families. The kidney-gene analysis revealed likely deleterious variants in known
      kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated
      fetuses. Kidney histology was similar in the latter 2 fetuses-presenting a
      distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1
      variants in one family and a GREB1L variant in another family. GREB1L and ROBO1
      were added to our kidney-gene panel and additional variants were identified. Next
      generation sequencing substantially contributes to identifying causes of fetal
      kidney anomalies. Genetic causes may be supported by histological examination of
      the kidneys. This is the first time that SLIT-ROBO signaling is implicated in
      human bilateral kidney agenesis.

PMID- 29194580
TI  - A systems medicine approach reveals disordered immune system and lipid metabolism
      in multiple sclerosis patients.
AB  - Identification of autoimmune processes and introduction of new autoantigens
      involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the
      design of new drugs to prevent unresponsiveness and side effects in patients. To
      find significant changes, we evaluated the autoantibody repertoires in newly
      diagnosed relapsing-remitting MS patients (NDP) and those receiving disease
      modifying therapy (RP). Through a random peptide phage library, a panel of NDP-
      and RP-specific peptides was identified, producing two protein data sets
      visualized using Gephi, based on protein--protein interactions in the STRING
      database. The top modules of NDP and RP networks were assessed using Enrichr.
      Based on the findings, a set of proteins, including ATP binding cassette
      subfamily C member 1 (ABCC1), neurogenic locus notch homologue protein 1
      (NOTCH1), hepatocyte growth factor receptor (MET), RAF proto-oncogene
      serine/threonine-protein kinase (RAF1) and proto-oncogene vav (VAV1) was found in
      NDP and was involved in over-represented terms correlated with cell-mediated
      immunity and cancer. In contrast, transcription factor RelB (RELB), histone
      acetyltransferase p300 (EP300), acetyl-CoA carboxylase 2 (ACACB), adiponectin
      (ADIPOQ) and phosphoenolpyruvate carboxykinase 2 mitochondrial (PCK2) had major
      contributions to viral infections and lipid metabolism as significant events in
      RP. According to these findings, further research is required to demonstrate the
      pathogenic roles of such proteins and autoantibodies targeting them in MS and to
      develop therapeutic agents which can ameliorate disease severity.

PMID- 29194582
TI  - Is there predictive value in early magnetic resonance imaging of the brain in
      infants born preterm?

PMID- 29194583
TI  - PharmCAT: A Pharmacogenomics Clinical Annotation Tool.
AB  - Implementation of genomic medicine into clinical care continues to increase in
      prevalence in medical centers worldwide. As defined by the National Human Genome
      Research Institute, "Genomic medicine is an emerging medical discipline that
      involves using genomic information about an individual as part of their clinical
      care...." The genomic information utilized falls broadly into two categories: 1)
      highly penetrant genetic disorders and 2) pharmacogenomics. Herein, we focus on
      pharmacogenomics, although the Pharmacogenomics Clinical Annotation Tool
      (PharmCAT) tool could be extended to include other types of genetic variation.

PMID- 29194581
TI  - Hodgkin lymphoma: A review and update on recent progress.
AB  - Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by
      cancerous Reed-Sternberg cells in an inflammatory background. Patients are
      commonly diagnosed with HL in their 20s and 30s, and they present with
      supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in
      advanced-stage disease, HL is highly curable with combination chemotherapy,
      radiation, or combined-modality treatment. Although the same doxorubicin,
      bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the
      mainstay of therapy over the last 30 years, risk-adapted approaches have helped
      de-escalate therapy in low-risk patients while intensifying treatment for higher
      risk patients. Even patients who are not cured with initial therapy can often be
      salvaged with alternate chemotherapy combinations, the novel antibody-drug
      conjugate brentuximab, or high-dose autologous or allogeneic hematopoietic stem
      cell transplantation. The programmed death-1 inhibitors nivolumab and
      pembrolizumab have both demonstrated high response rates and durable remissions
      in patients with relapsed/refractory HL. Alternate donor sources and reduced
      intensity conditioning have made allogeneic hematopoietic stem cell
      transplantation a viable option for more patients. Future research will look to
      integrate novel strategies into earlier lines of therapy to improve the HL cure
      rate and minimize long-term treatment toxicities. CA Cancer J Clin 2018;68:116
      132. (c) 2017 American Cancer Society.

PMID- 29194584
TI  - Model-Informed Reverse and Forward Translation of Safety Risks in Drug
      Development.
AB  - Despite major scientific investments, safety accounts for significant pipeline
      attrition, especially in late preclinical and early clinical development. Many
      failures are due to difficulty interpreting safety signals or difficulty
      optimizing schedules of compounds with narrow therapeutic margins. Model-informed
      translation can address these challenges, both through "forward" translation of
      early signals to future scenarios, as well as through "reverse" translation of
      safety data into mechanistic insight.

PMID- 29194586
TI  - Intraindividual Pharmacokinetic Variability: Focus on Small-Molecule Kinase
      Inhibitors.
AB  - The magnitude of interindividual pharmacokinetic variability (IIV) of a drug and
      the factors responsible for this variability are intensively studied before-and
      sometimes after-registration as crucial information in anticipating and
      understanding variability in toxicity and efficacy. However, there has been much
      less attention paid to intraindividual variability, reflecting random or
      systematic changes in an individual's pharmacokinetics over time. We have chosen
      to focus on small-molecule kinase inhibitors (SMKIs).

PMID- 29194585
TI  - Complex interactions between hypoxia-ischemia and inflammation in preterm brain
      injury.
AB  - : Children surviving preterm birth have a high risk of disability, particularly
      cognitive and learning problems. There is extensive clinical and experimental
      evidence that disability is now primarily related to dysmaturation of white and
      gray matter, defined by failure of oligodendrocyte maturation and neuronal
      dendritic arborization, rather than cell death alone. The etiology of this
      dysmaturation is multifactorial, with contributions from hypoxia-ischemia,
      infection/inflammation and barotrauma. Intriguingly, these factors can interact
      to both increase and decrease damage. In this review we summarize preclinical and
      clinical evidence that all of these factors trigger secondary or chronic
      inflammation and gliosis. Thus, we hypothesize that these shared pathological
      features play a key role in a final common pathway that leads to the impaired
      neural maturation and connectivity and cognitive/motor impairments that are
      commonly observed in infants born preterm. This raises the possibility that
      secondary or chronic inflammation may be a viable therapeutic target for delayed
      interventions to improve neurodevelopmental outcomes after preterm birth. WHAT
      THIS PAPER ADDS: Hypoxia-ischemia, infection/inflammation, and
      barotrauma/volutrauma all contribute to preterm brain injury. Multiple different
      triggers of preterm brain injury are associated with central nervous system
      dysmaturation. Secondary brain inflammation may be a viable target to improve
      neurodevelopment after preterm birth.

PMID- 29194587
TI  - Genetic association of molecular traits: A help to identify causative variants in
      complex diseases.
AB  - In the past 15 years, major progresses have been made in the understanding of the
      genetic basis of regulation of gene expression. These new insights have
      revolutionized our approach to resolve the genetic variation underlying complex
      diseases. Gene transcript levels were the first expression phenotypes that were
      studied. They are heritable and therefore amenable to genome-wide association
      studies. The genetic variants that modulate them are called expression
      quantitative trait loci. Their study has been extended to other molecular
      quantitative trait loci (molQTLs) that regulate gene expression at the various
      levels, from chromatin state to cellular responses. Altogether, these studies
      have generated a wealth of basic information on the genome-wide patterns of gene
      expression and their inter-individual variation. Most importantly, molQTLs have
      become an invaluable asset in the genetic study of complex diseases. Although the
      identification of the disease-causing variants on the basis of their overlap with
      molQTLs requires caution, molQTLs can help to prioritize the relevant candidate
      gene(s) in the disease-associated regions and bring a functional interpretation
      of the associated variants, therefore, bridging the gap between genotypes and
      clinical phenotypes.

PMID- 29194588
TI  - Reply to Opioid use among cancer survivors: A call to action for oncology and
      primary care providers.

PMID- 29194589
TI  - Pathological integration, or, how East Europeans use racism to become British.
AB  - East Europeans are integrating into life in the UK. This entails learning to get
      along with their new neighbours, but it also involves not getting along with
      certain neighbours. Integration is not confined to benevolent forms of everyday
      cosmopolitanism, multiculturalism and conviviality; it can also include more
      pathological forms, like racism. Whilst integration is generally seen as
      desirable, the learning that it entails necessarily includes less desirable
      practices and norms. The aim of this article is to show how East Europeans in the
      UK have been acquiring specifically British competencies of racism. This doesn't
      mean all East Europeans are racist or they always use racism; it does mean,
      however, that racism is a part of the integration equation. We focus on the
      racist and racializing practices of Poles, Hungarians and Romanians in Bristol in
      the UK. These East Europeans are using racism to insert themselves more
      favourably into Britain's racialized status hierarchies. This is a kind of
      integration.

PMID- 29194590
TI  - Effectiveness of Statins as Primary Prevention in People With Different
      Cardiovascular Risk: A Population-Based Cohort Study.
AB  - The purpose was to analyze statin effectiveness in a general population with
      differing levels of coronary heart disease (CHD) risk. Patients (35-74 years)
      without previous cardiovascular disease were included and stratified according to
      10-year CHD risk (<5%, 5-7.4%, 7.5-9.9%, and 10-19.9%). New users were
      categorized according to their medical possession ratio (MPR). The main outcome
      was atherosclerotic cardiovascular disease (ASCVD) (myocardial infarction and
      ischemic stroke). In adherent patients (MPR 70%), statin treatment decreased
      ASCVD risk across the range of coronary risk (from 16-30%). The 5-year number
      needed to treat (NNT) was 470 and 204 in the risk categories <5% and 5-7.4%,
      respectively, and 75 and 62 in the 7.5-9.9% category than in the 10-19.9%
      category, respectively. Statin therapy should remain a priority in patients at
      high 10-year CHD risk (10-19.9%). Most patients with intermediate risk could
      benefit from statin treatment, but the treatment decision should focus on the net
      benefit, safety, and patient preference, given the higher NNT.

PMID- 29194591
TI  - A mutational comparison of adult and adolescent and young adult (AYA) colon
      cancer.
AB  - BACKGROUND: It is possible that the relative lack of progress in treatment
      outcomes among adolescent and young adult (AYA) patients with cancer is caused by
      a difference in disease biology compared with the corresponding diseases in
      younger and older individuals. There is evidence that colon cancer is more
      aggressive and has a poorer prognosis in AYA patients than in older adult
      patients. METHODS: To further understand the molecular basis for this difference,
      whole-exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2
      pediatric colon cancers. RESULTS: A statistically significant difference in
      mutational frequency was observed between AYA and adult samples in 43 genes,
      including ROBO1, MYC binding protein 2 (MYCBP2), breast cancer 2 (early onset)
      (BRCA2), MAP3K3, MCPH1, RASGRP3, PTCH1, RAD9B, CTNND1, ATM, NF1; KIT, PTEN, and
      FBXW7. Many of these mutations were nonsynonymous, missense, stop-gain, or
      frameshift mutations that were damaging. Next, RNA sequencing was performed on a
      subset of the samples to confirm the mutations identified by exome sequencing.
      This confirmation study verified the presence of a significantly greater
      frequency of damaging mutations in AYA compared with adult colon cancers for 5 of
      the 43 genes (MYCBP2, BRCA2, PHLPP1, TOPORS, and ATR). CONCLUSIONS: The current
      results provide the rationale for a more comprehensive study with a larger sample
      set and experimental validation of the functional impact of the identified
      variants along with their contribution to the biologic and clinical
      characteristics of AYA colon cancer. Cancer 2018;124:1070-82. (c) 2017 American
      Cancer Society.

PMID- 29194592
TI  - Immunoglobulin free light chains in saliva: a potential marker for disease
      activity in multiple sclerosis.
AB  - A new procedure was developed and applied to study immunoglobulin free light
      chains (FLC) in saliva of healthy subjects and patients with multiple sclerosis
      (MS). The procedure was based on a Western blot analysis for detection and
      semiquantitative evaluation of monomeric and dimeric FLCs. The FLC indices
      accounting for the total FLC levels and for the monomer/dimer ratios of kappa and
      lambda FLC were calculated, and the cut-off values of the FLC indices were
      determined to distinguish healthy state from MS disease. The obtained FLC index
      values were statistically different in the saliva of three groups: active MS
      patients, MS patients in remission and healthy subjects groups. Our FLC monomer
      dimer analysis allowed differentiation between healthy state and active MS with
      specificity of 100% and a sensitivity of 88.5%. The developed technique may serve
      as a new non-invasive complementary tool to evaluate the disease state by
      differentiating active MS from remission with sensitivity of 89% and specificity
      of 80%.

PMID- 29194593
TI  - JAK3 and PI3K mediate bovine Interferon-tau stimulated gene expression in the
      blood neutrophils.
AB  - Interferon tau, a 23 kDa trophoblast derived protein diffuses out from the uterus
      into the circulation and leads to the expression of IFNtau stimulated genes viz.
      ISG15 and OAS1 in blood neutrophils. The IFNtau pathway is species as well as
      tissue specific. To unsnarl the IFNtau downstream signaling pathway, the blood
      neutrophils were incubated simultaneously with 10 ng/ml of recombinant bovine
      interferon tau and the inhibitors of JAK2 (AG490), JAK3 (CP690550), p38
      (SB202190), PI3K/Akt (LY294002), and MAPK/Erk (U0126) at specific doses for 4-hr
      duration. The IFNtau pathway was determined through real-time gene expression of
      ISG15 and OAS1; immunocytochemistry of ISG15; and Western blotting of ISG15,
      OAS1, pJAK3 and PI3K. The ISG15 and OAS1 expression decreased significantly (p <
      0.001) in the presence of pJAK3 and PI3K inhibitors as compared to a positive
      control where only interferon tau was used. Immunocytochemistry revealed an
      attenuated ISG15 response while stimulating blood neutrophils with pJAK3
      inhibitor (CP690550) and PI3K inhibitor (LY294002). Similarly, Western blot
      analysis of neutrophil protein fraction showed weak signals of ISG15, OAS1, pJAK3
      and PI3K in the presence of pJAK3 and PI3K inhibitors. The expression profile,
      immunocytochemistry and western blot analysis revealed a JAK3 and PI3K mediated
      interferon-tau stimulated gene expression in blood neutrophils.

PMID- 29194594
TI  - Development and Validation of a Short-Form Safety Net Medical Home Scale.
AB  - OBJECTIVE: To develop a short-form Safety Net Medical Home Scale (SNMHS) for
      assessing patient-centered medical home (PCMH) capability in safety net clinics.
      DATA SOURCES/STUDY SETTING: National surveys of federally qualified health
      centers (FQHCs). Interviews with FQHC directors. STUDY DESIGN: We constructed
      three short-form SNMHS versions and examined correlations with full SNMHS and
      related primary care assessments. We tested usability with FQHC directors and
      reviewed scale development with an advisory group. DATA COLLECTION: Federally
      qualified health center surveys were administered in 2009 and 2013, by mail and
      online. Usability testing was conducted through telephone interviews with FQHC
      directors in 2013. PRINCIPAL FINDINGS: Six-, 12-, and 18-question short-form
      SNMHS versions had Pearson correlations with full scale of 0.84, 0.92, and 0.96,
      respectively. All versions showed a level of convergent validity with other
      primary care assessment scales comparable to the full SNMHS. User testers found
      short forms to be low-burden, though missing some PCMH concepts. Advisory group
      members expressed caution over missing concepts and appropriate use of short-form
      self-assessments. CONCLUSIONS: Short-form versions of SNMHS showed strong
      correlations with full scale and may be useful for brief assessment of safety net
      PCMH capability. Each short-form SNMHS version may be appropriate for different
      research, quality improvement, and assessment purposes.

PMID- 29194595
TI  - The Roles of Participants' Differing Background Information in the Evaluation of
      Evidence.

PMID- 29194597
TI  - Re: Think before you leap.

PMID- 29194596
TI  - Truncated isoform Vav3.1 is highly expressed in ovarian cancer stem cells and
      clinically relevant in predicting prognosis and platinum-response.
AB  - Vav3 is a key modulator of GTP-hydrolases of the Rho/Rac family, which are
      crucially involved in cell proliferation. Vav3 is alternatively spliced in full
      length Vav3-alpha and N-terminal truncated Vav3.1 lacking its self-regulatory
      domains. The aim of our study was to estimate the clinical impact of Vav3 and all
      other Vav family members in ovarian cancer. Purification of a stem-cell like side
      population (SP) from ovarian cancer cell lines was performed by flow
      cytometry/FACS. Differences in gene expression between SP and NSP were assessed
      by Gene Array analysis and confirmed by RT-PCR and immunoblot. In addition, Vav
      mRNA expression was determined in 150 epithelial ovarian cancers.
      Clinicopathological parameters, platinum-sensitivity and survival were analyzed
      and associated with Vav expression. SP fractions of ovarian cancer cell lines
      exhibited marked overexpression of Vav3.1 (p < 0.001). Vav1 and Vav2 did not
      prove to be of clinicopathologic relevance in ovarian cancer. High Vav3.1
      expression correlated with higher FIGO stage and residual disease. Furthermore,
      Vav3.1 overexpression was associated with poor progression-free (HR = 2.820, p =
      0.0001) and overall survival (HR = 2.842, p = 0.0001). Subgroup analyses revealed
      an impact of Vav3.1 on survival in Type-II but not in Type-I cancers. Notably,
      platinum-refractory cancers showed marked overexpression of Vav3.1 compared to
      other subsets of platinum-sensitivity (15.848 vs. 6.653, p = 0.0001). In
      conclusion, Vav3.1 is over-expressed in stem-cell like SP fractions and is
      clinically relevant in the pathophysiology of ovarian cancer. The N-terminal
      truncated Vav3.1 may be decisively involved in mechanisms causing genuine multi
      drug resistance.

PMID- 29194598
TI  - Composition, Granular Structure, and Pasting Properties of Native Starch
      Extracted from Plectranthus edulis (Oromo dinich) Tubers.
AB  - : Chemical composition, granular morphology and pasting properties of native
      starch extracted from tubers of Plectranthus edulis were analyzed. Starch was
      extracted from tubers of 6 accessions collected from 4 different areas in
      Ethiopia. Particle size analysis (PSA) and cryo-scanning electron microscope
      (cryo-SEM) imaging were used to examine the granular morphology and visualize the
      starch paste, respectively. Pasting properties, water absorption, and gelation
      capacity were compared. A wide range was found for the amylose (14.2% to 23.9%),
      calcium (216 to 599), potassium (131 to 878), and phosphorus (1337 to 2090)
      contents (parts per million per dry matter). PSA showed a bimodal distribution
      containing small spherical (14.6 MUm) and large ellipse-shaped (190.4 MUm)
      granules. Major differences were found for the pasting with peak viscosities
      differing from 3184 to 7312 mPa?s. Starch from accessions Chencha and Inuka
      showed a difference in packing density as clearly seen through cryo-SEM image at
      75% of the peak viscosity (PV), and the granular integrity was mainly responsible
      for the significant difference in their PV and breakdown. Principal component
      analysis revealed 2 distinct groups: native starch extracted from accessions at
      the Wolayta zone (Inuka, Lofua, and Chenqoua) and other accessions (Jarmet, Arjo
      white, and Chencha). The study revealed the potential of P. edulis starch for its
      application in food industries. However, the inherent variation due to
      environmental conditions on physicochemical properties of the starch needs
      further investigation. PRACTICAL APPLICATION: Plectranthus edulis is cultivated
      in considerable amounts throughout Ethiopia, which makes it a valuable starch
      source. Due to its low tendency to retrograde, it could be applied in food
      industry as an equivalent for the current starch sources. Moreover, the low
      amylose content makes it preferable for an application in refrigerated foods as
      this unique quality trait prevents syneresis in end products during storage.
      Based on the significantly higher pasting temperature of the studied P. edulis
      starch extracts, it can form an alternative for potato starch, which is less
      suitable for its use in pasteurized foods.

PMID- 29194599
TI  - Teens and Spice: A Review of Adolescent Fatalities Associated with Synthetic
      Cannabinoid Use.
AB  - Synthetic cannabinoids (SCs) are commonly abused by adolescents with reported
      past year (2013) use in high school students between 3 and 10%. Standard
      adolescent postmortem toxicology does not include routine SC analysis, and thus,
      the true burden of fatalities related to SCs is unknown. A retrospective case
      review of two cases included scene investigation, interviews, autopsy, and
      toxicology. SCs were confirmed by liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). Review of the eight adolescent SC-associated fatalities in the
      literature revealed five of eight cases had no other discernible cause of death
      on autopsy. Compounds detected included PB-22 (1.1 ng/mL), JWH-210 (12 ng/mL),
      XLR-11 (1.3 ng/mL), JWH-122, AB-CHMINACA (8.2 ng/mL), UR-144 (12.3 ng/mL), and
      JWH-022 (3 ng/mL). With synthetic drug use on the rise, forensic experts should
      have a high index of suspicion for the possibility of SC intoxication in
      adolescent fatalities with no other discernible cause of death.

PMID- 29194600
TI  - First record of non-native hybrid catfish Pseudoplatystoma reticulatum * Leiarius
      marmoratus in the Upper Parana River basin, Brazil.
AB  - The aim of this study is to report the presence of a three non-native hybrid long
      whiskered catfishes (family Pimelodidae) in the Upper Parana River basin, Brazil.
      Genetic analyses demonstrated that the three presumptive hybrids were a result of
      the crossbreeding of Pseudoplatystoma reticulatum (central Amazonas River basin
      and Lower Parana River) and Leiarius marmoratus (Amazonas, Essequibo and Orinoco
      rivers), producing a hybrid commonly known in Brazil as cachandia. The potential
      threat to biodiversity, due to possible genetic contamination, competition and
      predation of wild stocks, of such artificially produced hybrid fishes is
      discussed.

PMID- 29194601
TI  - Idiopathic Intracranial Hypertension in Children and Adolescents: An Update.
AB  - PREMISE: Idiopathic intracranial hypertension (IIH), previously known as
      pseudotumor cerebri syndrome (PTC) is a serious neurological disorder that can
      lead to irreversible visual loss. Predominantly a disorder affecting women in
      reproductive years, the pediatric population is not spared. PROBLEM: In the past
      few years, the condition has been redefined, due to new accepted values for
      opening pressure in children and advances in neuroimaging. Emerging techniques in
      ophthalmology are being increasingly used to monitor disease in these patients.
      And, although the treatment tools have not changed in several years, important
      evidence for efficacy for acetazolamide finally came to light in recent years in
      the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). POTENTIAL
      SOLUTION: This review article provides an overview on recent advances in
      diagnosis, evaluation and treatment of IIH.

PMID- 29194602
TI  - Think before you leap.

PMID- 29194603
TI  - How to analyse the spatiotemporal tumour samples needed to investigate cancer
      evolution: A case study using paired primary and recurrent glioblastoma.
AB  - Many traits of cancer progression (e.g., development of metastases or resistance
      to therapy) are facilitated by tumour evolution: Darwinian selection of subclones
      with distinct genotypes or phenotypes that enable such progression.
      Characterising these subclones provide an opportunity to develop drugs to better
      target their specific properties but requires the accurate identification of
      somatic mutations shared across multiple spatiotemporal tumours from the same
      patient. Current best practices for calling somatic mutations are optimised for
      single samples, and risk being too conservative to identify shared mutations with
      low prevalence in some samples. We reasoned that datasets from multiple matched
      tumours can be used for mutual validation and thus propose an adapted two-stage
      approach: (1) low-stringency mutation calling to identify mutations shared across
      samples irrespective of the weight of evidence in a single sample; (2) high
      stringency mutation calling to further characterise mutations present in a single
      sample. We applied our approach to three-independent cohorts of paired primary
      and recurrent glioblastoma tumours, two of which have previously been analysed
      using existing approaches, and found that it significantly increased the amount
      of biologically relevant shared somatic mutations identified. We also found that
      duplicate removal was detrimental when identifying shared somatic mutations. Our
      approach is also applicable when multiple datasets e.g. DNA and RNA are available
      for the same tumour.

PMID- 29194604
TI  - Effects of microRNA-129 and its target gene c-Fos on proliferation and apoptosis
      of hippocampal neurons in rats with epilepsy via the MAPK signaling pathway.
AB  - This study aims to investigate the effect of microRNA-129 (miR-129) on
      proliferation and apoptosis of hippocampal neurons in epilepsy rats by targeting
      c-Fos via the MAPK signaling pathway. Thirty rats were equally classified into a
      model group (successfully established as chronic epilepsy models) and a normal
      group. Expression of miR-129, c-Fos, bax, and MAPK was detected by RT-qPCR and
      Western blotting. Hippocampal neurons were assigned into normal, blank, negative
      control (NC), miR-129 mimic, miR-129 inhibitor, siRNA-c-Fos, miR-129
      inhibitor+siRNA-c-Fos groups. The targeting relationship between miR-129 and c
      Fos was predicted and verified by bioinformatics websites and dual-luciferase
      reporter gene assay. Cell proliferation after transfection was measured by MTT
      assay, and cell cycle and apoptosis by flow cytometry. c-Fos is a potential
      target gene of miR-129. Compared with the normal group, the other six groups
      showed a decreased miR-129 expression; increased expression of expression of c
      Fos, Bax, and MAPK; decreased proliferation; accelerated apoptosis; more cells
      arrested in the G1 phase; and fewer cells arrested in the S phase. Compared with
      the blank and NC groups, the miR-129 mimic group and the siRNA-c-Fos group showed
      decreased expression of c-Fos, Bax, and MAPK, increased cells proliferation, and
      decreased cell apoptosis, fewer cells arrested in the G1 phase and more cells
      arrested in the S phase. However, the miR-129 inhibitor groups showed reverse
      consequences. This study suggests that miR-129 could inhibit the occurrence and
      development of epilepsy by repressing c-Fos expression through inhibiting the
      MAPK signaling pathway.

PMID- 29194605
TI  - How the expression of green fluorescent protein and human cardiac actin in the
      heart influences cardiac function and aerobic performance in zebrafish Danio
      rerio.
AB  - The present study examined how the expression of enhanced green fluorescent
      protein (eGFP) and human cardiac actin (ACTC) in zebrafish Danio rerio influences
      embryonic heart rate (RH ) and the swim performance and metabolic rate of adult
      fish. Experiments with the adults involved determining the critical swimming
      speed (Ucrit , the highest speed sustainable and measure of aerobic capacity)
      while measuring oxygen consumption. Two different transgenic D. rerio lines were
      examined: one expressed eGFP in the heart (tg(cmlc:egfp)), while the second
      expressed ACTC in the heart and eGFP throughout the body (tg(cmlc:actc,ba:egfp)).
      It was found that RH was significantly lower in the tg(cmlc:actc,ba:egfp) embryos
      4 days post-fertilization compared to wild-type (WT) and tg(cmlc:egfp). The swim
      experiments demonstrated that there was no significant difference in Ucrit
      between the transgenic lines and the wild-type fish, but metabolic rate and cost
      of transport (oxygen used to travel a set distance) was nearly two-fold higher in
      the tg(cmlc:actc,ba:egfp) fish compared to WT at their respective Ucrit . These
      results suggest that the expression of ACTC in the D. rerio heart and the
      expression of eGFP throughout the animal, alters cardiac function in the embryo
      and reduces the aerobic efficiency of the animal at high levels of activity.

PMID- 29194606
TI  - Induced mutation and epigenetics modification in plants for crop improvement by
      targeting CRISPR/Cas9 technology.
AB  - Clustered regularly interspaced palindromic repeats associated protein Cas9
      (CRISPR-Cas9), originally an adaptive immunity system of prokaryotes, is
      revolutionizing genome editing technologies with minimal off-targets in the
      present era. The CRISPR/Cas9 is now highly emergent, advanced, and highly
      specific tool for genome engineering. The technology is widely used to animal and
      plant genomes to achieve desirable results. The present review will encompass how
      CRISPR-Cas9 is revealing its beneficial role in characterizing plant genetic
      functions, genomic rearrangement, how it advances the site-specific mutagenesis,
      and epigenetics modification in plants to improve the yield of field crops with
      minimal side-effects. The possible pitfalls of using and designing CRISPR-Cas9
      for plant genome editing are also discussed for its more appropriate applications
      in plant biology. Therefore, CRISPR/Cas9 system has multiple benefits that mostly
      scientists select for genome editing in several biological systems.

PMID- 29194607
TI  - Contribution of Histidine and Lysine to the Generation of Volatile Compounds in
      Jinhua Ham Exposed to Ripening Conditions Via Maillard Reaction.
AB  - : To evaluate the role of Maillard reactions in the generation of flavor
      compounds in Jinhua ham, the reactions of glucose and ethanal with histidine and
      lysine, respectively, were studied by simulating the ripening conditions of
      Jinhua ham. The volatile products produced were analyzed using solid phase
      microextraction-gas chromatography/mass spectrometry. The results showed that 8
      volatile compounds were generated by the reaction of glucose and histidine and 10
      volatile compounds were generated by the reaction of glucose and lysine.
      Reactions of ethanal with lysine and with histidine both generated 31 volatile
      compounds that contributed to the flavor of Jinhua ham. This indicates that
      histidine and lysine related to Maillard reactions possibly play important roles
      in the generation of the unique flavor compounds in Jinhua ham. This research
      demonstrates that free amino acids participate in the generation of volatile
      compounds from Jinhua ham via the Maillard reaction and provides a basic
      mechanism to explain flavor formation in Jinhua ham. PRACTICAL APPLICATION:
      Jinhua ham is a well-known traditional Chinese dry-cured meat product. However,
      the formation of the compounds comprising its special flavor is not well
      understood. Our results indicate that Maillard reactions occur in Jinhua ham
      under ripening conditions. This work illustrates the contribution of Maillard
      reactions to the flavor of Jinhua ham.

PMID- 29194608
TI  - STR Genotyping from a Dry-Cleaned Skirt in a Sexual Assault Case.
AB  - In this sexual assault case, the standard preliminary semen examinations could
      not confirm physically or biochemically whether the accused's semen had stained
      the victim's skirt because the skirt had been dry-cleaned for stain removal and
      had been worn for more than a year after the assault. Fortunately, however, a
      photograph taken just after the assault was found in the court records that
      showed white stains on the checkered skirt. The locations of the stains were
      estimated based on the checkered pattern of the fabric, and microscopic
      examination using Baecchi's staining revealed the presence of spermatozoa.
      Further analysis indicated the male DNA profile generated from the sperm cells
      was consistent with the suspect's DNA using three multiplex STR typing systems
      for a total of 21 autosomal and 17 Y chromosomal short tandem repeats (STRs).
      Ultimately, the result of the DNA profile played a very useful role as additional
      evidence.

PMID- 29194609
TI  - Using the Connectivity Map to discover compounds influencing human osteoblast
      differentiation.
AB  - Osteoporosis is a common skeletal disorder characterized by low bone mass leading
      to increased bone fragility and fracture susceptibility. Identification of
      factors influencing osteoblast differentiation and bone formation is very
      important. Previously, we identified parbendazole to be a novel compound that
      stimulates osteogenic differentiation of human mesenchymal stromal cells (hMSCs),
      using gene expression profiling and bioinformatic analyzes, including the
      Connectivity Map (CMap), as an in-silico approach. The aim for this paper is to
      identify additional compounds affecting osteoblast differentiation using the
      CMap. Gene expression profiling was performed on hMSCs differentiated to
      osteoblasts using Illumina microarrays. Our osteoblast gene signature, the top
      regulated genes 6 hr after induction by dexamethasone, was uploaded into CMap
      (www.broadinstitute.org/cmap/). Through this approach we identified compounds
      with gene signatures positively correlating (withaferin-A, calcium folinate,
      amylocaine) or negatively correlating (salbutamol, metaraminol, diprophylline) to
      our osteoblast gene signature. All positively correlating compounds stimulated
      osteogenic differentiation, as indicated by increased mineralization compared to
      control treated cells. One of three negatively correlating compounds, salbutamol,
      inhibited dexamethasone-induced osteoblastic differentiation, while the other two
      had no effect. Based on gene expression data of withaferin-A and salbutamol, we
      identified HMOX1 and STC1 as being strongly differentially expressed . shRNA
      knockdown of HMOX1 or STC1 in hMSCs inhibited osteoblast differentiation. These
      results confirm that the CMap is a powerful approach to identify positively
      compounds that stimulate osteogenesis of hMSCs, and through this approach we can
      identify genes that play an important role in osteoblast differentiation and
      could be targets for novel bone anabolic therapies.

PMID- 29194611
TI  - TGFbeta signaling controls intrahepatic bile duct development may through
      regulating the Jagged1-Notch-Sox9 signaling axis.
AB  - Due to the inherent limitations of the mouse models, the molecular mechanism of
      TGFbeta signaling involved in the development of intrahepatic bile ducts (IHBDs)
      has been investigated little. Here, we investigated the role of TGFbeta signaling
      and its regulatory mechanism in IHBDs development. We demonstrate that TGFbeta
      signaling pathway activity is essential for IHBDs development. When blocking
      TGFbeta signaling at E10.5, the number of bile ducts in hilum was reduced more
      than two fold and number of CK19 positive chlangiocytes in periphery was reduced
      more than 3.5-fold compared with controls. We also show that alpha-smooth muscle
      actin (alpha-SMA)-immunoreactive cells are located in the portal vein mesenchyme
      (PVM) adjacent to the bile ducts during IHBDs development and identify the alpha
      SMA positive cells expressing the Notch ligand Jagged1 in the periportal area.
      Importantly, after blocking TGFbeta signaling, the expression of Jagged1 was
      selectively decreased in the PVM but not in biliary epithelial cells (BECs),
      which is associated with the transformation of portal mesenchyme cells (PMCs)
      into portal myofibroblasts (PMFs). In addition, Sox9, which is downstream of
      Notch, is decreased after blocking the TGFbeta signaling pathway in the liver.
      Our findings uncover a novel mechanism of TGFbeta signaling in controlling the
      development of IHBDs may through regulating the Jagged1-Notch-Sox9 signaling
      axis.

PMID- 29194610
TI  - Estimating the Cost Savings of Preventive Dental Services Delivered to Medicaid
      Enrolled Children in Six Southeastern States.
AB  - OBJECTIVE: To quantify the impact of multiyear utilization of preventive dental
      services on downstream dental care utilization and expenditures for children.
      DATA SOURCES/STUDY SETTING: We followed 0.93 million Medicaid-enrolled children
      who were 3-6 years old in 2005 from 2005 to 2011. We used Medicaid claims data of
      Alabama, Georgia, Mississippi, North Carolina, South Carolina, and Texas. STUDY
      DESIGN: We clustered each state's study population into four groups based on
      utilization of topical fluoride and dental sealants before caries-related
      treatment using machine learning algorithms. We evaluated utilization rates and
      expenditures across the four groups and quantified cost savings of preventive
      care for different levels of penetration. DATA EXTRACTION METHOD: We extracted
      all dental-related claims using CDT codes. PRINCIPAL FINDINGS: In all states,
      Medicaid expenditures were much lower for children who received topical fluoride
      and dental sealants before caries development than for all other children, with a
      per-member per-year difference ranging from $88 for Alabama to $156 for
      Mississippi. CONCLUSIONS: The cost savings from topical fluoride and sealants
      across the six states ranged from $1.1M/year in Mississippi to $12.9M/year in
      Texas at a 10 percent penetration level. Preventive dental care for children not
      only improves oral health outcomes but is also cost saving.

PMID- 29194612
TI  - Nanocurcumin restores aberrant miRNA expression profile in multiple sclerosis,
      randomized, double-blind, placebo-controlled trial.
AB  - In the current study, we aimed to identify nanocurcumin effects on microRNAs
      (miRNAs) in the peripheral blood of patients with relapsing-remitting multiple
      sclerosis (RRMS). We intended to investigate the expression pattern of these
      miRNAs in experimental settings in vivo. The expression levels of the selected 27
      miRNAs known to be involved in the regulation of immune responses were analyzed
      in 50 RRMS patients and 35 healthy controls. The miRNA expression profiles were
      investigated by quantitative PCR (qPCR) at baseline and after 6 months of
      nanocurcumin therapy. Our data revealed that the expression of a number of
      microRNAs including miR-16, miR-17-92, miR-27, miR-29b, miR-126, miR-128, miR
      132, miR-155, miR-326, miR-550, miR-15a, miR-19b, miR-106b, miR-320a, miR-363,
      miR-31, miR-150, and miR-340 is regulated by nanocurcumin. The results of the
      current work indicate that nanocurcumin is able to restore the expression pattern
      of dysregulated miRNAs in MS patients. We discovered that some miRNAs are
      deregulated in untreated patients compared with healthy controls and nanocurcumin
      treated patients. This is a new finding that might represent the potential
      contribution of these miRNAs to MS pathogenesis. Taken together, these data
      provide novel insights into miRNA-dependent regulation of the function of B and T
      cells in MS disease and enrich our understanding of the effects mediated by a
      therapeutic approach that targets B and T cells.

PMID- 29194613
TI  - Comparison of vegetable shortening and cocoa butter as vehicles for cortisol
      manipulation in Salmo trutta.
AB  - This study demonstrates that vegetable shortening and cocoa butter are two
      effective vehicles for intraperitoneal cortisol implants in juvenile teleosts,
      specifically brown trout Salmo trutta, residing in north temperate freshwater
      environments. Each vehicle showed a different pattern of cortisol elevation.
      Vegetable shortening was found to be a more suitable vehicle for long-term
      cortisol elevation [elevated at 3, 6 and 9 days post treatment (dpt)], while
      cocoa butter may be better suited for short-term cortisol elevation (only
      elevated at 3 dpt). Additionally, plasma cortisol levels were higher with
      cortisol-vegetable shortening than with cortisol-cocoa butter implants. Plasma
      glucose levels were elevated 6 and 9 dpt for fishes injected with cortisol
      vegetable shortening, but did not change relative to controls and shams in
      cortisol-cocoa butter fishes. In conclusion, vegetable shortening and cocoa
      butter are both viable techniques for cortisol manipulation in fishes in
      temperate climates, providing researchers with different options depending on
      study objectives.

PMID- 29194614
TI  - Immunomodulatory effects of foreskin mesenchymal stromal cells on natural killer
      cells.
AB  - Foreskin-mesenchymal stromal cells (FSK-MSCs) are immune-privileged thus making
      them valuable immunotherapeutic cell product. Characterization of the
      relationship between FSK-MSCs and natural killer (NK) cells is essential to
      improve cell-based therapy. In the present study, we studied for the first time
      FSK-MSCs-NK interaction and showed that the result of such cross talk was
      robustly dependent on the type of cytokines (IL-2, IL-12, IL-15, and IL-21)
      employed to activate NK cells. Distinctly activated-NK cells showed uneven
      cytotoxicity against FSK-MSCs, triggering their death in fine. The expression of
      different cell-surface ligands (CD112, CD155, ULPB-3) and receptors (LAIR, KIRs)
      ensuring such interaction was altered following co-culture of both populations.
      Despite their partial negative effect on NK cell proliferation, FSK-MSCs boosted
      the capacity of activated NK-cells to secrete IFN-gamma and TNF-alpha. Moreover,
      FSK-MSCs enhanced degranulation of NK cells, reinforced secretion of perforin and
      granzymes, while only modestly increased ROS production. On the other hand, FSK
      MSCs-mediated expression of C1 and B9 serpins was significantly lowered in the
      presence of activated NK cells. Altogether, our results highlight major
      immunological changes following FSK-MSCs-NK interaction. Understanding these
      outcomes will therefore enhance the value of the therapeutic strategy.

PMID- 29194615
TI  - The Impact of WIC on Infant Immunizations and Health Care Utilization.
AB  - OBJECTIVE: To test how prenatal participation in the Special Supplemental
      Nutrition Program for Women, Infants and Children (WIC) impacts health care
      utilization and immunizations within the first year of an infant's life. DATA
      SOURCE: We utilize comprehensive South Carolina Medicaid claims data from 2004 to
      2013 linked with birth certificates data from 2004 to 2012. These data contain
      information on WIC participation and all health care utilization within the first
      year of an infant's life. STUDY DESIGN: We employ a maternal fixed-effects
      empirical design to control for unobserved factors that influence WIC
      participation and health care utilization. PRINCIPAL FINDINGS: We estimate that
      WIC participation increases infant health care utilization within the first year
      of life by 0.20 well-child visits (95 percent CI 0.16-0.23), by 0.22 vaccinations
      (95 percent CI 0.17-0.27), and by increasing the probability of receiving care in
      an emergency room by 2.9 percentage points (95 percent CI 2.0-3.8). Additionally,
      our results show that WIC participation decreases the average number of days an
      infant spends in the hospital within his or her first year of life by 0.41 days
      (95 percent CI 0.22-0.60). CONCLUSIONS: These findings suggest that WIC may
      increase health care costs in some dimensions while reducing it in others, and
      more work is needed to fully evaluate the impact of the program on future
      expenditures.

PMID- 29194616
TI  - Comparative analysis of single-cell RNA sequencing data from mouse spermatogonial
      and mesenchymal stem cells to identify differentially expressed genes and
      transcriptional regulators of germline cells.
AB  - Identifying effective internal factors for regulating germline commitment during
      development and for maintaining spermatogonial stem cells (SSCs) self-renewal is
      important to understand the molecular basis of spermatogenesis process, and to
      develop new protocols for the production of the germline cells from other cell
      sources. Therefore, this study was designed to investigate single-cell RNA
      sequencing data for identification of differentially expressed genes (DEGs) in 12
      mouse-derived single SSCs (mSSCs) in compare with 16 mouse-derived single
      mesenchymal stem cells. We also aimed to find transcriptional regulators of DEGs.
      Collectively, 1,584 up-regulated DEGs were identified that are associated with 32
      biological processes. Moreover, investigation of the expression profiles of genes
      including in spermatogenesis process revealed that Dazl, Ddx4, Sall4, Fkbp6,
      Tex15, Tex19.1, Rnf17, Piwil2, Taf7l, Zbtb16, and Cadm1 are presented in the
      first 30 up-regulated DEGs. We also found 12 basal transcription factors (TFs)
      and three sequence-specific TFs that control the expression of DEGs. Our findings
      also indicated that MEIS1, SMC3, TAF1, KAT2A, STAT3, GTF3C2, SIN3A, BDP1, PHC1,
      and EGR1 are the main central regulators of DEGs in mSSCs. In addition, we
      collectively detected two significant protein complexes in the protein-protein
      interactions network for DEGs regulators. Finally, this study introduces the
      major upstream kinases for the main central regulators of DEGs and the components
      of core protein complexes. In conclusion, this study provides a molecular
      blueprint to uncover the molecular mechanisms behind the biology of SSCs and
      offers a list of candidate factors for cell type conversion approaches and
      production of germ cells.

PMID- 29194617
TI  - A clinico-pathologic study of placenta percreta.
AB  - OBJECTIVE: To review a single-center case series of placenta percreta and to
      evaluate risk factors and the impact of surgical techniques used in previous
      cesarean delivery. METHODS: The present retrospective cohort study included
      pregnancies with placenta percreta managed between January 1, 2002, and March 31,
      2017, at Saint Luc University Hospital, Brussels, Belgium. The data reviewed
      included demographics, outcomes, inter-pregnancy interval, and surgical
      techniques used for uterine closure in previous cesarean delivery. A cases series
      of non-accreta placenta previa was used as a control group. RESULTS: There were
      19 pregnancies included in the study. The most common ultrasonography signs in
      the study group were loss of the clear zone (14/17; 82%), placental lacunae
      (17/17; 100%), and subplacental hypervascularity (11/14; 79%). Median gravidity,
      parity, and number of previous cesarean deliveries were higher (P<0.05) and inter
      pregnancy interval was longer (P<0.05) in the study group than the control group.
      There was no difference between the groups in the surgical techniques used for
      previous cesarean deliveries. CONCLUSION: The prenatal ultrasonography diagnosis
      of placenta percreta is accurate and facilitates optimal management by a
      specialized multidisciplinary team. Multicenter studies are required to further
      evaluate the impact of the surgical techniques used for prior cesarean delivery
      on the risks of placenta percreta in subsequent pregnancies.

PMID- 29194618
TI  - Narrower insight to SIRT1 role in cancer: A potential therapeutic target to
      control epithelial-mesenchymal transition in cancer cells.
AB  - The epithelial-mesenchymal transition (EMT) is a highly networked cellular
      process which involves cell transition from the immotile epithelial to the motile
      mesenchymal phenotype, whereby cells lose their cell-cell adhesion and cell
      polarity. This important process is one of the underlying mechanisms for enabling
      invasion and metastasis of cancer cells which is considered as malignant phase of
      tumor progression. However, the molecular mechanisms of this process are not
      fully clarified. It is reported that Sirtuin1 (SIRT1), a NAD+ dependent class III
      histone deacetylase is associated with tumor metastasis through positive
      regulation of EMT in several types of cancers. Recent studies confirmed that up
      and down regulation of SIRT1 expression remarkably change the migration ability
      of different cancer cells in vitro and tumor metastasis in vivo. Also, according
      to this fact that carcinomas as the main human solid tumors, originate from
      different epithelial cell types, SIRT1 role in EMT has received a great attention
      due to its potential role in tumor development and metastasis. Therefore, SIRT1
      has been proposed as a key regulator of cancer metastasis by promoting EMT,
      although little is known about the cleared effect of SIRT1 in this transition.
      Our aim in this review is to explain in more detail the role of SIRT1 in various
      signaling pathways related to carcinogenesis, with the focus on the promoting
      role of SIRT1 in EMT as a potential therapeutic target to control EMT and to
      prevent cancer progression.

PMID- 29194619
TI  - Direct Conservative Domain in the Continuous Galerkin Method for Groundwater
      Models.
AB  - The continuous Galerkin finite element method is commonly considered locally
      nonconservative because a single element with fluxes computed directly from its
      potential distribution is unable to conserve its mass and fluxes across edges
      that are discontinuous. Some literature sources have demonstrated that the
      continuous Galerkin method can be locally conservative with postprocessed fluxes.
      This paper proposes the concept of a direct conservative domain (DCD), which
      could conserve mass when fluxes are computed directly from the potential
      distribution. Also presented here is a method for modifying the advection fluxes
      to obtain different conservative domains from the DCDs. Furthermore, DCDs are
      used to analyze the local conservation of several postprocessing algorithms, for
      which DCDs provide the theoretical basis. The local conservation of DCDs and the
      proposed method are illustrated and verified by using a hypothetical 2-D model.

PMID- 29194620
TI  - Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases.
AB  - For many years, a considerable number of patients with autoimmune diseases (ADs)
      have suffered from a lack of drug response and drug-related toxicity. Despite the
      emergence of new therapeutic options such as biological agents, patients continue
      to struggle with these problems. Unfortunately, new challenges, including the
      paradoxical effects of biological drugs, have complicated the situation. In
      recent decades, efforts have been made to predict drug response as well as drug
      related side effects. Thanks to the many advances in genetics, evaluation of
      markers to predict drug response/toxicity before the initiation of treatment may
      be an avenue toward personalizing treatments. Implementing pharmacogenetics and
      pharmacogenomics in the clinic could improve clinical care; however, obstacles
      remain to effective personalized medicine for ADs. The present study attempted to
      clarify the concept of pharmacogenetics/pharmacogenomics for ADs. After an
      overview on the pathogenesis of the most common types of treatments, this paper
      focuses on pharmacogenetic studies related to the selected ADs. Bridging the gap
      between pharmacogenetics and personalized medicine is also discussed. Moreover,
      the advantages, disadvantages and recommendations related to making personalized
      medicine practical for ADs have been addressed.

PMID- 29194621
TI  - Effects of the Medicare Modernization Act on Spending for Outpatient Surgery.
AB  - OBJECTIVES: To examine the effects of Medicare's revised ambulatory surgery
      center (ASC) payment schedule on overall payments for outpatient surgery. DATA
      SOURCES: Twenty percent sample of national Medicare beneficiaries. STUDY DESIGN:
      We conducted a pre-post study of Medicare beneficiaries who underwent outpatient
      surgery in a hospital outpatient department (HOPD), ASC, or physician office
      between 2004 and 2011. Specifically, we used multivariable regression to compare
      temporal trends in outpatient surgery before and after implementation of
      Medicare's revised payment schedule in 2008, which reduced ASC facility payments
      to roughly two-thirds that of HOPDs. Our outcome measures included overall
      Medicare payments, utilization rates, per beneficiary spending, and average
      episode payments for outpatient surgery. PRINCIPAL FINDINGS: Between the last
      quarters of 2007 and 2008, overall Medicare payments for outpatient surgery grew
      by $334 million-an amount nearly three times higher than would have been expected
      without the policy change (p < .001 for the difference). While utilization rates
      of outpatient surgery were attenuated, per beneficiary spending and average
      surgical episode payments increased by 10.4 percent and 7.8 percent,
      respectively, over the same period. By the end of 2011, Medicare payments for
      outpatient surgery reached $5.1 billion. Without the policy change, they would
      have totaled only $4.1 billion. CONCLUSIONS: Despite lessening demand, reduced
      ASC facility payments did not curb spending for outpatient surgery. In fact,
      overall payments actually increased following the policy change, driven by higher
      average episode payments.

PMID- 29194622
TI  - Ceratocorys mariaovidiorum sp. nov. (Gonyaulacales), a new dinoflagellate species
      previously reported as Protoceratium reticulatum.
AB  - The family Ceratocoryaceae includes the genera Ceratocorys, Protoceratium, and
      Schuettiella, whose phylogenetic relationships are poorly known. Here, the new
      non-yessotoxin-producing species of the genus Ceratocorys, Ceratocorys
      mariaovidiorum sp. nov., previously reported as the toxic Protoceratium
      reticulatum, is described from examinations by light and scanning electron
      microscopy, molecular phylogeny, and toxin analyses. The species description is
      made from culture samples of strains CCMP1740 and CCMP404 from USA waters.
      Ceratocorys mariaovidiorum is globular and has thick and strongly reticulated
      plates with one pore within each reticule, just like P. reticulatum, but the key
      difference between the two species is the presence of five precingular plates in
      C. mariaovidiorum instead of six as in P. reticulatum. The thecal plate formula
      is Po, 4', 0a, 5", 6c, ~7s, 5''', 0p, 2''''. The apical pore plate is oval with a
      lambda-shaped pore. The first apical plate is narrow with a ventral pore on the
      right anterior side; it contacts the apical pore plate and its contact with the
      anterior sulcal plate is slight or absent. The fourth precingular plate of other
      Gonyaulacales is absent. Ceratocorys mariaovidiorum may have small spines on the
      second antapical plate. A phylogenetic study based on internal transcribed
      spacer/5.8SrDNA supports the morphological classification of C. mariaovidiorum as
      a new species of Ceratocorys and in a different clade from P. reticulatum.

PMID- 29194623
TI  - Phase II trial of preoperative chemoradiation plus perioperative SOX chemotherapy
      in patients with locally advanced gastric cancer.
AB  - BACKGROUND AND PURPOSE: The ideal treatment strategy of patients with locally
      advanced gastric adenocarcinoma is unclear. The aim of this study is to evaluate
      the efficacy and feasibility of preoperative chemoradiation in these patients.
      PATIENTS AND METHODS: All patients underwent laparoscopic exploration or
      exploratory laparotomy before chemoradiation. Patients received one cycle of S-1
      and oxalipatin followed by concurrent radiation and chemotherapy, then underwent
      another cycle of S-1 and oxalipatin. Surgery was performed 6-8 weeks after
      completing radiochemotherapy. The rate of curative gastrectomy and survival were
      investigated. This trial was registered with ClinicalTrial.gov, number
      NCT02024217. RESULTS: From April 2012 to August 2014, 40 patients were enrolled
      in the trial, and 36 patients were assessable. The most common hematologic toxic
      effects were leukopenia (80.6%), neutropenia (69.4%), and thrombocytopenia (50%);
      the most common nonhematologic toxic effects were anorexia (50%), nausea (22.3%),
      and vomiting (13.9%). There were no treatment related deaths. A total of 33
      patients underwent second exploratory laparotomy after preoperative
      chemoradiation, and 24 (67%) patients received curative gastrectomy. The rates of
      pathological complete response (pCR) were 13.9%. The medial survival time (MST)
      was 30.3 months. CONCLUSION: Preoperative chemoradiation may be an effective
      treatment strategy among patients with locally advanced gastric adenocarcinoma.

PMID- 29194624
TI  - A Three-Locus, PCR-based Method for Forensic Identification of Plant Material.
AB  - Plant residue is currently an underutilized resource in forensic investigations
      despite the fact that many crime scenes, as well as suspects and victims, harbor
      plant-derived residue that could be recovered and analyzed. Notwithstanding the
      considerable skill of forensic botanists, current methods of species
      determination could benefit from tools for DNA-based species identification.
      However, DNA barcoding in plants has been hampered by sequence complications in
      the plant genome. Following a database search for usable barcodes, broad-spectrum
      primers were designed and utilized to amplify and sequence the rbcL, trnL-F, and
      rrn18 genetic loci from a variety of household plants. Once obtained, these DNA
      sequences were used to design species-targeted primers that could successfully
      discriminate the source of plant residue from among the 21 species tested.

PMID- 29194625
TI  - Laryngeal chondronecrosis after radiation therapy in a dog.
AB  - A 5-year-old pug presented with a soft tissue swelling on the ventral neck and
      moderate stridor with associated respiratory effort. This patient received
      hypofractionated radiotherapy for metastatic upper lip mast cell tumour and to
      the submandibular lymph nodes 6 months before presentation. Oral examination
      showed moderate elongation of the soft palate, stage III laryngeal collapse with
      only the right laryngeal saccule mildly everted and exuberant pale epiglottal and
      left pharyngeal mucosa. Staphylectomy, resection of the epiglottal mucosa and
      left arytenoid lateralisation were performed. One day after surgery, temporary
      tracheostomy was performed after respiratory distress due to the severe laryngeal
      and pharyngeal oedema. A third oral exam showed pale and redundant caudal
      pharyngeal mucosa obstructing the rima glottis, soft and collapsible arytenoid
      cartilage with pale mucosa and bilateral everted laryngeal saccules. Permanent
      tracheostomy was elected and laryngeal cartilage biopsies were taken. Histologic
      diagnosis showed cartilage necrosis and abundant tissue oedema. The patient was
      euthanased 1 week later.

PMID- 29194626
TI  - Using proprioception to get a better grasp on embodiment.

PMID- 29194627
TI  - Heading in the right direction: the importance of direction selectivity for
      cerebellar motor learning.

PMID- 29194629
TI  - UbiGate: a synthetic biology toolbox to analyse ubiquitination.
AB  - Ubiquitination is mediated by an enzymatic cascade that results in the
      modification of substrate proteins, redefining their fate. This post
      translational modification is involved in most cellular processes, yet its
      analysis faces manifold obstacles due to its complex and ubiquitous nature.
      Reconstitution of the ubiquitination cascade in bacterial systems circumvents
      several of these problems and was shown to faithfully recapitulate the process.
      Here, we present UbiGate - a synthetic biology toolbox, together with an
      inducible bacterial expression system - to enable the straightforward
      reconstitution of the ubiquitination cascades of different organisms in
      Escherichia coli by 'Golden Gate' cloning. This inclusive toolbox uses a
      hierarchical modular cloning system to assemble complex DNA molecules encoding
      the multiple genetic elements of the ubiquitination cascade in a predefined
      order, to generate polycistronic operons for expression. We demonstrate the
      efficiency of UbiGate in generating a variety of expression elements to
      reconstitute autoubiquitination by different E3 ligases and the modification of
      their substrates, as well as its usefulness for dissecting the process in a time-
      and cost-effective manner.

PMID- 29194628
TI  - The presynaptic scaffolding protein Piccolo organizes the readily releasable pool
      at the calyx of Held.
AB  - KEY POINTS: Bassoon and Piccolo do not mediate basal synaptic vesicle release at
      a high-frequency synapse. Knockdown of Bassoon increases short-term depression at
      the calyx of Held. Both Bassoon and Piccolo have shared functions in synaptic
      vesicle replenishment during high-frequency synaptic transmission. Piccolo
      organizes the readily releasable pool of synaptic vesicles. It safeguards a
      fraction of them to be not immediately available for action potential-induced
      release. This enables the synapse to sustain high-frequency synaptic transmission
      over long periods. ABSTRACT: Synaptic vesicles (SVs) are released at the active
      zone (AZ), a specialized region of the presynaptic plasma membrane organized by a
      highly interconnected network of multidomain proteins called the cytomatrix of
      the active zone (CAZ). Two core components of the CAZ are the large, highly
      homologous scaffolding proteins Bassoon and Piccolo, whose function is not well
      understood. To investigate their role in synaptic transmission, we established
      the small hairpin RNA (shRNA)-mediated in vivo knockdown (KD) of Bassoon and
      Piccolo at the rat calyx of Held synapse. KD of Bassoon and Piccolo, separately
      or simultaneously, did not affect basic SV release. However, short-term
      depression (STD) was prominently increased by the KD of Bassoon, whereas KD of
      Piccolo only had a minor effect. The observed alterations in STD were readily
      explained by reduced SV replenishment in synapses deficient in either of the
      proteins. Thus, the regulation of SV refilling during ongoing synaptic activity
      is a shared function of Bassoon and Piccolo, although Bassoon appears to be more
      efficient. Moreover, we observed the recruitment of slowly-releasing SVs of the
      readily-releasable pool (RRP), which are normally not available for action
      potential-induced release, during high-frequency stimulation in Piccolo-deficient
      calyces. Therefore, the results obtained in the present study suggest a novel and
      specific role for Piccolo in the organization of the subpools of the RRP.

PMID- 29194630
TI  - Major vascular resections in retroperitoneal sarcoma.
AB  - Retroperitoneal sarcomas (RPS) frequently involve major vessels, which either
      originate from them or secondarily encase or invade them. In this field, major
      vascular resections result in increased morbidity. However, survival does not
      seem to be affected by the need for vascular resection or by this higher
      morbidity. This paper aims to provide descriptions of the surgical strategy and
      outcomes for retroperitoneal sarcomas involving major vessels.

PMID- 29194631
TI  - Rapid authentication of edible bird's nest by FTIR spectroscopy combined with
      chemometrics.
AB  - BACKGROUND: Edible bird's nests (EBNs) have been traditionally regarded as a kind
      of medicinal and healthy food in China. For economic reasons, they are frequently
      subjected to adulteration with some cheaper substitutes, such as Tremella fungus,
      agar, fried pigskin, and egg white. As a kind of precious and functional product,
      it is necessary to establish a robust method for the rapid authentication of EBNs
      with small amounts of samples by simple processes. In this study, the Fourier
      transform infrared spectroscopy (FTIR) system was utilized and its feasibility
      for identification of EBNs was verified. RESULTS: FTIR spectra data of authentic
      and adulterated EBNs were analyzed by chemometrics analyses including principal
      component analysis, linear discriminant analysis (LDA), support vector machine
      (SVM) and one-class partial least squares (OCPLS). The results showed that the
      established LDA and SVM models performed well and had satisfactory classification
      ability, with the former 94.12% and the latter 100%. The OCPLS model was
      developed with prediction sensitivity of 0.937 and specificity of 0.886. Further
      detection of commercial EBN samples confirmed these results. CONCLUSION: FTIR is
      applicable in the scene of rapid authentication of EBNs, especially for quality
      supervision departments, entry-exit inspection and quarantine, and customs
      administration. (c) 2017 Society of Chemical Industry.

PMID- 29194632
TI  - Endothelial Piezo1 channels as sensors of exercise.
AB  - Piezo1 channels are newly discovered ion channels which have come to the fore as
      players in endothelial biology. They have a key role as sensors of shear stress,
      a frictional force which arises in vascular biology because of blood flow.
      Endothelial Piezo1 channels are critical in murine embryonic development, just
      after the heart starts to beat and drive blood into the nascent endothelial
      network. In contrast they are not critical at the adult stage but they are
      important for performance in whole body physical activity where they have a
      vascular bed-specific effect to cause mesenteric resistance artery
      vasoconstriction, achieved through opposition to the vasodilatory mechanism of
      endothelium-derived hyperpolarization. These are our first insights into the
      relevance of endothelial Piezo1 channels and there is clearly much more to be
      done to understand the significance and underlying molecular mechanisms. The
      suggestion that they constitute an exercise sensor by virtue of their shear
      stress-sensing capability is intriguing and could open the way to better
      understanding of the molecular basis of the response to exercise and
      determination of how the health benefits of exercise arise. Enhanced Piezo1
      channel activity has been demonstrated in response to the Yoda1 molecule and this
      suggests the possibility for developing tools which probe and manipulate this
      aspect of the exercise system. Whether such agents might progress to 'exercise
      pills' and whether the existence of such pills would be desirable are matters for
      further work and debate.

PMID- 29194633
TI  - Systemic therapy in retroperitoneal sarcoma management.
AB  - There is paucity of randomized controlled data on the role of systemic therapy in
      retroperitoneal sarcomas. The type of systemic therapy used is guided by the
      histological subtype. The majority of retroperitoneal sarcomas comprising
      liposarcomas and leiomyosarcomas are by and large chemotherapy insensitive. There
      is an urgent need for more efficacious systemic therapies in the management of
      early and advanced stage retroperitoneal sarcomas.

PMID- 29194634
TI  - Proteasome-independent functions of lysine-63 polyubiquitination in plants.
AB  - Contents Summary 995 I. Introduction 995 II. The plant Ub machinery 996 III. From
      Ub to Ub linkage types in plants 997 IV. Increasing analytical resolution for K63
      polyUb in plants 998 V. How to build K63 polyUb chains? 998 VI. Cellular roles of
      K63 polyUb in plants 999 VII. Physiological roles of K63 polyUb in plants 1004
      VIII. Future perspectives: towards the next level of the Ub code 1006
      Acknowledgements 1006 References 1007 SUMMARY: Ubiquitination is a post
      translational modification essential for the regulation of eukaryotic proteins,
      having an impact on protein fate, function, localization or activity. What
      originally appeared to be a simple system to regulate protein turnover by the 26S
      proteasome is now known to be the most intricate regulatory process cells have
      evolved. Ubiquitin can be arranged in countless chain assemblies, triggering
      various cellular outcomes. Polyubiquitin chains using lysine-63 from ubiquitin
      represent the second most abundant type of ubiquitin modification. Recent studies
      have exposed their common function in proteasome-independent functions in non
      plant model organisms. The existence of lysine-63 polyubiquitination in plants
      is, however, only just emerging. In this review, we discuss the recent advances
      on the characterization of ubiquitin chains and the molecular mechanisms driving
      the formation of lysine-63-linked ubiquitin modifications. We provide an overview
      of the roles associated with lysine-63 polyubiquitination in plant cells in the
      light of what is known in non-plant models. Finally, we review the crucial roles
      of lysine-63 polyubiquitin-dependent processes in plant growth, development and
      responses to environmental conditions.

PMID- 29194635
TI  - OsCERK1 plays a crucial role in the lipopolysaccharide-induced immune response of
      rice.
AB  - Plant cell surface receptor-like kinases (RLKs) mediate the signals from microbe
      associated molecular patterns (MAMPs) that induce immune responses.
      Lipopolysaccharide (LPS), the major constituent of the outer membrane of gram
      negative bacteria, is a common MAMP perceived by animals and plants; however, the
      plant receptors/co-receptors are unknown except for LORE, a bulb-type lectin S
      domain RLK (B-lectin SD1-RLK) in Arabidopsis. OsCERK1 is a multifunctional RLK in
      rice that contains lysin motifs (LysMs) and is essential for the perception of
      chitin, a fungal MAMP, and peptidoglycan, a bacterial MAMP. Here, we analyzed the
      relevance of OsCERK1 to LPS perception in rice. Using OsCERK1-knockout mutants
      (oscerk1), we evaluated hydrogen peroxide (H2 O2 ) production and gene expression
      after LPS treatment. We also examined the LPS response in knockout mutants for
      the B-lectin SD1-RLK genes in rice and for all LysM-protein genes in Arabidopsis.
      Compared with wild-type rice cells, LPS responses in oscerk1 cells were mostly
      diminished. By contrast, rice lines mutated in either of three B-lectin SD1-RLK
      genes and Arabidopsis lines mutated in the LysM-protein genes responded normally
      to LPS. From these results, we conclude that OsCERK1 is an LPS receptor/co
      receptor and that the LPS perception systems of rice and Arabidopsis are
      significantly different.

PMID- 29194636
TI  - Benthic flattened cells of the phylogenetically related marine dinoflagellates
      Protoceratium reticulatum and Ceratocorys mariaovidiorum (Gonyaulacales): a new
      type of cyst?
AB  - A planktonic-benthic relationship has been described for many dinoflagellate
      species as part of their ecological strategy to overcome highly variable aquatic
      environments. Here, the phylogenetically and morphologically related marine
      dinoflagellates Protoceratium reticulatum and Ceratocorys mariaovidiorum were
      studied in relation to an unknown benthic life form. In vivo and fixed samples
      from cultures were analyzed in detail by light and scanning electron microscopy.
      In both species, a cell type with a morphology different from that of vegetative
      cells was observed in cultures grown until stationary phase. This cell type was
      always benthic, swimming sporadically only when it was disturbed. Its main
      feature included a strong dorsoventral compression. These cells originated from
      vegetative cells whose protoplasm underwent a progressive flattening, resulting
      in a gradual detachment of the reticulate and thick thecal plates and the
      formation of very thin non-reticulated new plates with pores. When returned to
      fresh full-strength medium, the cells recovered their spherical vegetative-like
      morphology, including new reticulated thick plates and subsequent cell divisions.
      The kinetics of flattened cell formation showed that in both species, this cell
      type increased exponentially until the onset of the culture stationary phase and
      then decreased. The results of this study are discussed in the context of the
      planktonic-benthic coupling in dinoflagellate life cycles, including those newly
      appreciated to be well adapted to the benthic environment.

PMID- 29194638
TI  - Divided stimulus control: Which key did you peck, or what color was it?
AB  - Responding on concurrent schedules produced a conditional discrimination (Phases
      1 and 2), asking either which peck produced the event, or which color the keys
      were when the event was produced. In Phases 3 and 4, reinforcer delivery or a
      delay in blackout was interpolated between responding and the conditional
      discrimination. In Phase 1, location versus color discrimination accuracy was
      controlled by the relative reinforcer frequency for correct responses to these
      questions (divided stimulus control). In Phases 2 to 4, relative reinforcer
      frequency for correct responses to these questions was .5, and the relative
      frequency with which concurrent-schedule responses produced the questions was
      varied. This variation had no clear effect on the accuracy of reporting Location
      or Color. These results are consistent with the model of divided control
      suggested by Davison and Elliffe (2010). Arranging a 3-s reinforcer between
      responding and choice decreased both color and location accuracy, but a 3-s delay
      only decreased location accuracy. Thus, in concurrent-schedule performance, both
      ambient stimuli prior to a reinforcer and the location of the just-reinforced
      response are available as discriminative stimuli following the reinforcer.
      Control of postreinforcer responding is divided between these according to their
      association with the relative frequency of subsequent reinforcers.

PMID- 29194637
TI  - Antioxidant and anti-inflammatory activities of freeze-dried grapefruit phenolics
      as affected by gum arabic and bamboo fibre addition and microwave pretreatment.
AB  - BACKGROUND: Recent epidemiological studies have suggested that phenolic compounds
      present in grapefruit play an important role in the bioactive properties of this
      fruit. However, the consumption of fresh grapefruit is low. Freeze-dried powdered
      grapefruit can be an alternative to promote this fruit consumption. To improve
      the quality and stability of the powdered fruit, encapsulating and anticaking
      agents can be added. In the present study, different grapefruit powders obtained
      by freeze-drying with the addition of gum arabic (1.27 g per 100 g) and bamboo
      fibre (0.76 g per 100 g) with and without a pre-drying microwave treatment were
      compared with the fresh and freeze-dried fruit with no carriers added, aiming to
      evaluate the effect of these preservation processes on phenolics content and on
      its antioxidant [1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing ability of
      plasma (FRAP)] and anti-inflamatory (evaluated in RAW 264.7 macrophages)
      capacities. RESULTS: Freeze-drying and gum arabic and bamboo fibre addition
      significantly increased total phenolics, as well as the antioxidant and anti
      inflammatory activities (by inhibiting nitric oxide production of
      lipopolysaccharide activated RAW 264.7 macrophages), of grapefruit. An additional
      increase in these parameters was obtained with microwave pretreatment before
      freeze-drying. CONCLUSIONS: The combined addition of gum arabic and bamboo fibre
      to grapefruit puree and the application of a microwave pretreatment improve the
      functional properties of the fruit without showing cytotoxicity in vitro. (c)
      2017 Society of Chemical Industry.

PMID- 29194639
TI  - Effect of fermentation on anthocyanin stability and in vitro bioaccessibility
      during shalgam (salgam) beverage production.
AB  - BACKGROUND: Shalgam is a traditional lactic acid fermented beverage highly
      popular in southern Turkey. The main raw material, black carrot, contains a
      significant amount of anthocyanins. In this study, changes in polyphenols,
      including anthocyanins, related total antioxidant capacity (TAC), and in vitro
      bioaccessibility during shalgam fermentation and main raw material were
      evaluated. RESULTS: Compared with the last 12 days of the fermentation, a higher
      increase in total phenolic content (TPC), anthocyanins content (AC), and TAC was
      observed in the first 12 days of the fermentation during shalgam production.
      Although black carrot exhibited the highest total flavonoid content (TFC), TPC,
      AC, and TAC values before bioaccessibility tests, the recovery of shalgam
      beverage was found to be mostly identical with black carrot results in terms of
      flavonoids, phenolics, and anthocyanins and antioxidant capacity after in vitro
      digestion. In vitro digestion significantly reduced the recovery of initial
      samples in terms of TFC, TPC, AC, and TAC analysis. The amount of beneficial
      compound in the early fermentation stage was significantly lower than with end
      product. Sixteen different phenolics were detected from shalgam beverage samples
      in high-performance liquid chromatography analysis. After performing
      bioaccessibility tests, only five phenolics were detected. As anthocyanins, only
      cyanidin content was identified. CONCLUSION: The degradation of phenolics and
      anthocyanins was observed after bioaccessibility tests. (c) 2017 Society of
      Chemical Industry.

PMID- 29194640
TI  - The Microvine, a plant model to study the effect of vine-shoot extract on the
      accumulation of glycosylated aroma precursors in grapes.
AB  - BACKGROUND: The Microvine plant model displays unique reproductive organ behavior
      and is suitable for grapevine fruit physiological studies, allowing one to
      undertake studies up to five times more rapidly than the current situation with
      grapevines. Recently, vine-shoot aqueous extracts, which have an interesting
      phenolic and aroma composition, have been proposed as viticultural biostimulants,
      since their post-veraison foliar application to grapevines impacts the wine aroma
      profile. Using Microvines, the aim of this study was to determine the effect of
      vine-shoot extract foliar application on 21 stages of grape development. The
      application was carried out from BBCH 53 (inflorescences clearly visible) to BBCH
      85 (softening of berries) to reveal stage-specific responses of the accumulation
      of glycosylated aroma precursors at BBCH 89 (berries ripe for harvest), the
      phenological stage selected to study the treatment effect. RESULTS: Microvine use
      made it possible to carry out 15 sampling time points during 86 days of the
      experiment, which were established by the cumulative degree days (CDD) parameter.
      The results confirmed that vine-shoot extract treatment had a positive impact on
      total glycosylated compounds, especially aglycones such as alcohols, terpenes and
      C13 -norisoprenoids, with a higher effect when the treatment was applied during
      ripening. CONCLUSION: Extrapolation of the results to grapevines suggests that
      vine-shoot extract treatment could modulate the synthesis of grape glycosylated
      aroma precursors. (c) 2017 Society of Chemical Industry.

PMID- 29194641
TI  - Chemometric analysis of minerals in gluten-free products.
AB  - BACKGROUND: Numerous studies indicate mineral deficiencies in people on a gluten
      free (GF) diet. These deficiencies may indicate that GF products are a less
      valuable source of minerals than gluten-containing products. In the study, the
      nutritional quality of 50 GF products is discussed taking into account the
      nutritional requirements for minerals expressed as percentage of recommended
      daily allowance (%RDA) or percentage of adequate intake (%AI) for a model celiac
      patient. Elements analyzed were calcium, potassium, magnesium, sodium, copper,
      iron, manganese, and zinc. Analysis of %RDA or %AI was performed using principal
      component analysis (PCA) and hierarchical cluster analysis (HCA). RESULTS: Using
      PCA, the differentiation between products based on rice, corn, potato, GF wheat
      starch and based on buckwheat, chickpea, millet, oats, amaranth, teff, quinoa,
      chestnut, and acorn was possible. In the HCA, four clusters were created. The
      main criterion determining the adherence of the sample to the cluster was the
      content of all minerals included to HCA (K, Mg, Cu, Fe, Mn); however, only the Mn
      content differentiated four formed groups. CONCLUSION: GF products made of
      buckwheat, chickpea, millet, oats, amaranth, teff, quinoa, chestnut, and acorn
      are better source of minerals than based on other GF raw materials, what was
      confirmed by PCA and HCA. (c) 2017 Society of Chemical Industry.

PMID- 29194642
TI  - Gene analysis and structure prediction for the cold-adaption mechanism of trypsin
      from the krill Euphausia superba (Dana, 1852).
AB  - BACKGROUND: The ability of Antarctic krill, Euphausia superba (Dana, 1852), to
      thrive in a cold environment comes from its capacity to synthesize cold-adapted
      enzymes. Its trypsin, as a main substance in the metabolic reactions, plays a key
      role in the adaption to low temperatures. However, the progress of research on
      its cold-adaption mechanism is being influenced due to the limited information on
      its gene and spatial structure. RESULTS: We studied the gene of E. superba
      trypsin with transcriptome sequencing first, and then discussed its cold-adaption
      mechanism with the full gene and predicted structure basing on bioinformatics.
      The results showed the proportion of certain residues played important roles in
      the cold-adaptation behavior for trypsin. Furthermore, a higher proportion of
      random coils and reduced steric hindrance might also be key factors promoting its
      cold adaption. CONCLUSION: This research aimed to reveal the cold-adaption
      mechanism of E. superba trypsin and provide support for basic research on
      molecular modification by site-directed mutagenesis of complementary DNA used to
      produce new and improved recombinant variants with cold adaption. Furthermore, it
      may broaden its commercial application on minimizing undesirable changes elevated
      at higher temperature in food processing and in treatment of trauma and
      inflammation in medicine. (c) 2017 Society of Chemical Industry.

PMID- 29194643
TI  - Quantification of Tetradesmus obliquus (Chlorophyceae) cell size and lipid
      content heterogeneity at single-cell level.
AB  - Much of our current knowledge of microbial growth is obtained from studies at a
      population level. Driven by the realization that processes that operate within a
      population might influence a population's behavior, we sought to better
      understand Tetradesmus obliquus (formerly Scenedesmus obliquus) physiology at the
      cellular level. In this work, an accurate pretreatment method to quantitatively
      obtain single cells of T. obliquus, a coenobia-forming alga, is described. These
      single cells were examined by flow cytometry for triacylglycerol (TAG),
      chlorophyll, and protein content, and their cell sizes were recorded by coulter
      counter. We quantified heterogeneity of size and TAG content at single-cell level
      for a population of T. obliquus during a controlled standard batch cultivation.
      Unexpectedly, variability of TAG content per cell within the population increased
      throughout the batch run, up to 400 times in the final stage of the batch run,
      with values ranging from 0.25 to 99 pg . cell-1 . Two subpopulations, classified
      as having low or high TAG content per cell, were identified. Cell size also
      increased during batch growth with average values from 36 to 70 MUm3  . cell-1 ;
      yet cell size variability increased only up to 16 times. Cell size and cellular
      TAG content were not correlated at the single-cell level. Our data show clearly
      that TAG production is affected by cell-to-cell variation, which suggests that
      its control and better understanding of the underlying processes may improve the
      productivity of T. obliquus for industrial processes such as biodiesel
      production.

PMID- 29194644
TI  - Independent signalling cues underpin arbuscular mycorrhizal symbiosis and large
      lateral root induction in rice.
AB  - Perception of arbuscular mycorrhizal fungi (AMF) triggers distinct plant
      signalling responses for parallel establishment of symbiosis and induction of
      lateral root formation. Rice receptor kinase CHITIN ELICITOR RECEPTOR KINASE 1
      (CERK1) and alpha/beta-fold hydrolase DWARF14-LIKE (D14L) are involved in pre
      symbiotic fungal perception. After 6 wk post-inoculation with Rhizophagus
      irregularis, root developmental responses, fungal colonization and
      transcriptional responses were monitored in two independent cerk1 null mutants; a
      deletion mutant lacking D14L, and with D14L complemented as well as their
      respective wild-type cultivars (cv Nipponbare and Nihonmasari). Here we show that
      although essential for symbiosis, D14L is dispensable for AMF-induced root
      architectural modulation, which conversely relies on CERK1. Our results
      demonstrate uncoupling of symbiosis and the symbiotic root developmental
      signalling during pre-symbiosis with CERK1 required for AMF-induced root
      architectural changes.

PMID- 29194645
TI  - Detection and Identification of Psilocybe cubensis DNA Using a Real-Time
      Polymerase Chain Reaction High Resolution Melt Assay.
AB  - Psilocybe cubensis, or "magic mushroom," is the most common species of fungus
      with psychedelic characteristics. Two primer sets were designed to target
      Psilocybe DNA using web-based software and NBCI gene sequences. DNA was extracted
      from eighteen samples, including twelve mushroom species, using the Qiagen
      DNeasy(r) Plant Mini Kit. The DNA was amplified by the polymerase chain reaction
      (PCR) using the primers and a master mix containing either a SYBR(r) Green I,
      RadiantTM Green, or LCGreen Plus(r) intercalating dye; amplicon size was
      determined using agarose gel electrophoresis. The PCR assays were tested for
      amplifiability, specificity, reproducibility, robustness, sensitivity, and
      multiplexing with primers that target marijuana. The observed high resolution
      melt (HRM) temperatures for primer sets 1 and 7 were 78.85 +/- 0.31 degrees C and
      73.22 +/- 0.61 degrees C, respectively, using SYBR(r) Green I dye and 81.67 +/-
      0.06 degrees C and 76.04 +/- 0.11 degrees C, respectively, using RadiantTM Green
      dye.

PMID- 29194646
TI  - Conservative management of placenta percreta.
AB  - BACKGROUND: Maternal outcomes after conservative management of placenta percreta
      are poorly understood. OBJECTIVE: To assess the success and complication rates of
      conservative management of placenta percreta. SEARCH STRATEGY: The PubMed,
      MEDLINE, and Scopus databases were searched for English-language articles
      published between January 1990 and December 2016, using combinations of search
      terms related to conservative management of placenta percreta. SELECTION
      CRITERIA: Only studies describing conservative treatment for placenta percreta
      (without placental removal) were included in the systematic review. DATA
      COLLECTION AND ANALYSIS: There were 44 studies included and maternal outcomes
      were reviewed and categorized among 72 patients. MAIN RESULTS: The uterus was
      preserved among 42 (58%) patients and severe complications developed among 40
      (56%). Prophylactic uterine artery embolization (UAE) did not improve success
      rates (P=0.807); however, the mean time for complete placental resorption was
      lower in the UAE group than in the non-UAE group (22.4 weeks vs 35.3 weeks;
      P=0.014). Hysterectomy was performed at a mean of 44.6 days after cesarean
      delivery. Among the 23 patients with hysterectomy-related complications, 18 (78%)
      experienced bladder injury, intraoperative bleeding (>2000 mL), or both. The use
      of chemotherapy did not improve success rates (P=0.064). CONCLUSIONS: The present
      systematic review revealed high maternal morbidity during conservative management
      of placenta percreta.

PMID- 29194647
TI  - The RAS mutation status predicts survival in patients undergoing hepatic
      resection for colorectal liver metastases: The results from a genetic analysis of
      all-RAS.
AB  - INTRODUCTION: We investigated the impact of mutations in KRAS exons 3-4 and NRAS
      exons 2-3 in addition to KRAS exon 2, so-called all-RAS mutations, in patients
      with colorectal liver metastasis (CLM) undergoing hepatic resection. METHODS: We
      analyzed 421 samples from CLM patients for their all-RAS mutation status to
      compare the overall survival rate (OS), recurrence-free survival rate (RFS), and
      the pattern of recurrence between the patients with and without RAS mutations.
      RESULTS: RAS mutations were detected in 191 (43.8%). Thirty-two rare mutations
      (12.2%) were detected in 262 patients with KRAS exon 2 wild-type. After excluding
      79 patients who received anti-EGFR antibody therapy, 168 were classified as all
      RAS wild-type, and 174 as RAS mutant-type. A multivariate analysis of factors
      associated with OS and RFS identified the RAS status as an independent factor
      (OS; hazard ratio [HR] = 1.672, P = 0.0031, RFS; HR = 1.703, P = 0.0024).
      Recurrence with lung metastasis was observed significantly more frequent in
      patients with RAS mutations than in patients with RAS wild-type (P = 0.0005).
      CONCLUSIONS: Approximately half of CLM patients may have a RAS mutation. CLM
      patients with RAS mutations had a significantly worse survival rate in comparison
      to patients with RAS wild-type, regardless of the administration of anti-EGFR
      antibody therapy.

PMID- 29194648
TI  - High-performance serial block-face SEM of nonconductive biological samples
      enabled by focal gas injection-based charge compensation.
AB  - A longstanding limitation of imaging with serial block-face scanning electron
      microscopy is specimen surface charging. This charging is largely due to the
      difficulties in making biological specimens and the resins in which they are
      embedded sufficiently conductive. Local accumulation of charge on the specimen
      surface can result in poor image quality and distortions. Even minor charging can
      lead to misalignments between sequential images of the block-face due to image
      jitter. Typically, variable-pressure SEM is used to reduce specimen charging, but
      this results in a significant reduction to spatial resolution, signal-to-noise
      ratio and overall image quality. Here we show the development and application of
      a simple system that effectively mitigates specimen charging by using focal gas
      injection of nitrogen over the sample block-face during imaging. A standard gas
      injection valve is paired with a precisely positioned but retractable application
      nozzle, which is mechanically coupled to the reciprocating action of the serial
      block-face ultramicrotome. This system enables the application of nitrogen gas
      precisely over the block-face during imaging while allowing the specimen chamber
      to be maintained under high vacuum to maximise achievable SEM image resolution.
      The action of the ultramicrotome drives the nozzle retraction, automatically
      moving it away from the specimen area during the cutting cycle of the knife. The
      device described was added to a Gatan 3View system with minimal modifications,
      allowing high-resolution block-face imaging of even the most charge prone of
      epoxy-embedded biological samples.

PMID- 29194650
TI  - Evolution on the bright side of life: microorganisms and the evolution of
      mutualism.
AB  - Mutualistic interactions, where two interacting species have a net beneficial
      effect on each other's fitness, play a crucial role in the survival and evolution
      of many species. Despite substantial empirical and theoretical work in past
      decades, the impact of these interactions on natural selection is not fully
      understood. In addition, mutualisms between microorganisms have been largely
      ignored, even though they are ecologically important and can be used as tools to
      bridge the gap between theory and empirical work. Here, I describe two problems
      with our current understanding of natural selection in mutualism and highlight
      the properties of microbial mutualisms that could help solve them. One problem is
      that bias and methodological problems have limited our understanding of the
      variety of mechanisms by which species may adapt to mutualism. Another problem is
      that it is rare for experiments testing coevolution in mutualism to address
      whether each species has adapted to evolutionary changes in its partner. These
      problems can be addressed with genome resequencing and time-shift experiments,
      techniques that are easier to perform in microorganisms. In addition, microbial
      mutualisms may inspire novel insights and hypotheses about natural selection in
      mutualism.

PMID- 29194649
TI  - Localization of the glucosinolate biosynthetic enzymes reveals distinct spatial
      patterns for the biosynthesis of indole and aliphatic glucosinolates.
AB  - Glucosinolates constitute the primary defense metabolites in Arabidopsis thaliana
      (Arabidopsis). Indole and aliphatic glucosinolates, biosynthesized from
      tryptophan and methionine, respectively, are known to serve distinct biological
      functions. Although all genes in the biosynthetic pathways are identified, and it
      is known where glucosinolates are stored, it has remained elusive where
      glucosinolates are produced at the cellular and tissue level. To understand how
      the spatial organization of the different glucosinolate biosynthetic pathways
      contributes to their distinct biological functions, we investigated the
      localization of enzymes of the pathways under constitutive conditions and, for
      indole glucosinolates, also under induced conditions, by analyzing the spatial
      distribution of several fluorophore-tagged enzymes at the whole plant and the
      cellular level. We show that key steps in the biosynthesis of the different types
      of glucosinolates are localized in distinct cells in separate as well as
      overlapping vascular tissues. The presence of glucosinolate biosynthetic enzymes
      in parenchyma cells of the vasculature may assign new defense-related functions
      to these cell types. The knowledge gained in this study is an important
      prerequisite for understanding the orchestration of chemical defenses from site
      of synthesis to site of storage and potential (re)mobilization upon attack.

PMID- 29194651
TI  - Antenatal anemia increases the risk of receiving postpartum red blood cell
      transfusions although the overall risk of transfusion is low.
AB  - BACKGROUND: The objective was to determine if antenatal anemia is associated with
      postpartum red blood cell (RBC) transfusion. STUDY DESIGN AND METHODS: Women who
      gave birth at a regional, tertiary care maternity hospital between December 1,
      2015, and September 31, 2016, with a documented antenatal hemoglobin (Hb)
      concentration were included. Women were grouped into those who were either anemic
      (Hb < 11.0 g/dL) or nonanemic. The change in Hb concentration and RBC transfusion
      rates were compared between the anemic and nonanemic women, as well as by the
      mode of delivery (vaginal vs. Cesarean). To estimate the volume of blood loss in
      a normal delivery, the mean postpartum Hb concentration decrease for the not
      transfused women was calculated by subtracting the nadir postpartum Hb
      concentration from the antenatal Hb concentration and averaging these
      concentrations according to delivery route. RESULTS: Of 8039 cases analyzed, 1562
      (19%) had antenatal anemia and 6477 (81%) were nonanemic. Of the anemic women, 57
      (3.6%) received an RBC transfusion compared to 49 (0.76%) of the nonanemic women
      (p = 0.0001; odds ratio, 4.97; 95% confidence interval, 3.38-7.31). Antenatal
      anemia was significantly associated with receiving an RBC transfusion regardless
      of mode of delivery for those who delivered vaginally (p = 0.0001) or by Cesarean
      (p = 0.0001) compared to those who were nonanemic. The mean postpartum Hb
      concentration decrease was 1.12 +/- 1.12 g/dL for vaginal deliveries and 1.34 +/-
      0.21 g/dL for Cesarean deliveries in the not transfused women (p = 0.0001).
      CONCLUSION: Although the overall rate of transfusion was low, antenatal anemia
      was significantly associated with receiving a postpartum RBC transfusion.

PMID- 29194652
TI  - Outcomes of red blood cell transfusions prescribed in organ donors by the Digital
      Intern, an electronic decision support algorithm.
AB  - BACKGROUND: The Digital Intern (DI) is an electronic decision support tool for
      the management of organ donors. One algorithm determines the dose, in units of
      red blood cells to be transfused, based on hematocrit (Hct) thresholds and
      targets. The effectiveness of the transfusion dose calculated by the DI in terms
      of achieving the selected Hct target and the duration of the targeted dose is not
      known. STUDY DESIGN AND METHODS: This was a retrospective study to describe the
      outcomes of transfusions prescribed by the DI. Pre- and posttransfusion Hct
      levels were compared to define response and all posttransfusion Hct values were
      plotted to evaluate the duration of the prescribed dose. RESULTS: A total of 120
      organ donors were studied and 22 donors had 28 transfusions (six were transfused
      twice). The transfused donors were a mix of trauma and medical admissions and
      brain death and cardiac death donors. The transfusion target of 24% Hct was
      attained in 96% of transfusions. The mean number of units transfused was 1.4 and
      the mean time from transfusion to procurement was 19.8 hours. There was a decline
      in Hct over time after transfusion in all but one case with a mean decline of
      1.9% Hct over 13 hours. Six donors were transfused twice, likely due to a longer
      donor time period (41.7 hr vs. 27 hr). CONCLUSIONS: The DI provided transfusion
      dosing that achieved the desired threshold in the majority of organ donors
      transfused. Ongoing work focuses on application of this technology to
      transfusions in general patient populations.

PMID- 29194653
TI  - Electrophysiological markers predicting impeding AV-block during ablation of
      atrioventricular nodal reentry tachycardia.
AB  - BACKGROUND: Radiofrequency (RF) ablation of the slow pathway (SP) in
      atrioventricular nodal reentry tachycardia (AVNRT) is occasionally complicated
      with atrioventricular block (AVB) often predicted by junctional beats (JB) with
      loss of ventriculo-atrial (VA) conduction. METHODS: We analyzed retrospectively
      153 patients undergoing ablation of SP for typical AVNRT. Patients were divided
      into two age groups: 127 <= 70 years and 26 > 70 years. We analyzed the interval
      between the atrial electrogram in the His-bundle position and the distal ablation
      catheter [A(H)-A(RFd)] and between the distal ablation catheter and the proximal
      coronary sinus catheter [A(RFd)-A(CS)] before RF applications with and without
      JB. We evaluated if these intervals can be used as predictors of JB incidence and
      also of JB with loss of VA conduction. We also assessed if age influences the
      risk of loss of VA conduction. RESULTS: The A(H)-A(RFd) and A(RFd)-A(CS)
      intervals were significantly shorter in RF applications causing JB than those
      without JB (33 +/- 11 ms vs 39 +/- 9 ms, P < 0.001, 14 +/- 9 ms vs 20 +/- 7 ms, P
      < 0.001, respectively). The A(H)-A(RFd) and A(RFd)-A(CS) intervals were also
      significantly shorter in RFs causing JB with VA block than those with VA
      conduction (29 +/- 11 ms vs 35 +/- 11 ms, P < 0.001, 8 +/- 8 ms vs 17 +/- 8 ms, P
      < 0.001, respectively). Patients > 70 years had shorter intervals (36 +/- 11 ms
      vs 29 +/- 8 ms, P  =  0.012, 17 +/- 8 ms vs 13 +/- 7 ms, P  =  0.027,
      respectively), while VA block was more common in this age group. CONCLUSIONS: The
      A(H)-A(RFd) and A(RFd)-A(CS) intervals can be used as markers for predicting JB
      occurrence as well as impending AVB. JB with loss of VA conduction occur more
      often in older patients possibly due to a higher position of SP.

PMID- 29194654
TI  - Safety and efficacy analysis of one-stop intervention for treating nonvalvular
      atrial fibrillation.
AB  - BACKGROUND: Nonvalvular atrial fibrillation (AF) is a common arrhythmia. The
      treatment strategy for AF mainly includes controlling symptoms and decreasing the
      rate of complications. Our study aimed to evaluate the safety and efficacy of
      combination treatment of catheter ablation and left atrial appendage (LAA)
      closure (one-stop intervention) in patients with nonvalvular AF. METHODS AND
      RESULTS: Thirty-four patients with symptomatic AF (mean CHA2 DS2 -VASc score 4.1
      +/- 1.3, mean HAS-BLED score 3.8 +/- 1.2) were included. Patients first received
      radiofrequency-based left atrial ablation, and then the Watchman device (Boston
      Scientific, Natick, MA, USA) or AMPLATZER Cardiac Plug (ACP) (St. Jude Medical,
      Inc., St. Paul, MN, USA) was implanted for LAA closure. Follow-up was performed
      at 45 days and 3 months after LAA closure to assess for recurrence of AF and
      prevent stroke. Radiofrequency ablation and LAA closure were successful in 100%
      of patients without evidence of residual flow at the final transesophageal
      echocardiography evaluation. A Watchman device was implanted in 29 (85.3%)
      patients, and an ACP was implanted in five (14.7%) patients. No device-related
      thrombus formation or embolization was identified at the 45-day or 3-month follow
      up. Serious complications, including death, transient ischemic attack, ischemic
      or hemorrhagic stroke, or major bleeding, were also not identified during the
      follow-ups. CONCLUSION: For symptomatic patients with nonvalvular AF and a high
      risk of stroke, the one-stop intervention is feasible, safe, and efficacious.

PMID- 29194655
TI  - A classic textbook flutter.

PMID- 29194656
TI  - Head motion correction based on filtered backprojection for x-ray CT imaging.
AB  - PURPOSE: For head x-ray CT imaging, the head needs to remain motionless during
      the scan. In clinical practice, however, head motion is sometimes unavoidable
      depending on the patient. The motion can occur abruptly during the scan and can
      be unpredictable. It thereby causes motion artifacts such as tissue blurring or
      doubled edges around the skull area. To mitigate this problem, we propose a 3D
      head motion estimation (ME) and compensation algorithm based on filtered
      backprojection. METHODS: If a patient moves his or her head during the scan, a
      motion-corrupted sinogram is obtained. Modeling the head motion as a 3D rigid
      transformation, we develop a motion-compensated (MC) reconstruction algorithm
      based on the FDK algorithm. To determine the head motion of a rigid
      transformation, we propose two optimization-based ME schemes depending on the
      degree of head motion, both of which are performed by updating motion parameters
      and the corresponding MC reconstructed image alternatively until the proposed
      cost function is minimized for the MC reconstructed image. In particular, to
      improve the robustness in the case of large motion, we propose attaching a
      fiducial marker to the head so that more reliable motion parameters can be
      initialized by determining the marker position, before the optimization. To
      evaluate the proposed algorithm, a numerical phantom with realistic, continuous,
      and smoothly varying motion, and a moving physical phantom are used with a gantry
      rotation time of 1 s. RESULTS: In the simulation using a numerical phantom and in
      the experiment using a physical phantom, the proposed algorithm provides well
      restored 3D motion-compensated images in both cases of small and large motion. In
      particular, in the case of large motion of the physical phantom, using a fiducial
      marker, we obtain remarkable improvement of image quality in cerebral arteries
      and a lesion as well as the skull. Quantitative evaluations using the image
      sharpness and root-mean-square error also show noticeable improvement of image
      quality in both simulations and experiments. CONCLUSIONS: We propose a framework
      for head motion correction in an axial CT scan, which consists of motion
      estimation and compensation steps. Two image-based ME algorithms for rigid motion
      tracking are developed according to the degree of head motion. The estimated
      motion information is then used for MC image reconstruction. Both motion
      estimation and compensation algorithms are based on computationally efficient
      filtered backprojection. Excellent performance of the proposed framework is
      illustrated by means of simulations using a numerical phantom and experiments
      using a physical phantom.

PMID- 29194657
TI  - A proposal to create an extension to the European baseline series.
AB  - BACKGROUND: The current European baseline series consists of 30 allergens, and
      was last updated in 2015. OBJECTIVES: To use data from the European Surveillance
      System on Contact Allergies (ESSCA) to propose an extension to the European
      baseline series in response to changes in environmental exposures. METHODS: Data
      from departmental and national extensions to the baseline series, together with
      some temporary additions from departments contributing to the ESSCA, were
      collated during 2013-2014. RESULTS: In total, 31689 patients were patch tested in
      46 European departments. Many departments and national groups already consider
      the current European baseline series to be a suboptimal screen, and use their own
      extensions to it. The haptens tested are heterogeneous, although there are some
      consistent themes. Potential haptens to include in an extension to the European
      baseline series comprise sodium metabisulfite, formaldehyde-releasing
      preservatives, additional markers of fragrance allergy, propolis, Compositae mix,
      and 2-hydroxyethyl methacrylate. CONCLUSION: In combination with other published
      work from the ESSCA, changes to the current European baseline series are proposed
      for discussion. As well as addition of the allergens listed above, it is
      suggested that primin and clioquinol should be deleted from the series, owing to
      reduced environmental exposure.

PMID- 29194658
TI  - Mycorrhizal tomato plants fine tunes the growth-defence balance upon N depleted
      root environments.
AB  - In low nutritive environments, the uptake of N by arbuscular mycorrhizal (AM)
      fungi may confer competitive advantages for the host. The present study aims to
      understand how mycorrhizal tomato plants perceive and then prepare for an N
      depletion in the root environment. Plants colonized by Rhizophagus irregularis
      displayed improved responses to a lack of N than nonmycorrhizal (NM) plants.
      These responses were accomplished by a complex metabolic and transcriptional
      rearrangement that mostly affected the gibberellic acid and jasmonic acid
      pathways involving DELLA and JAZ1 genes, which were responsive to changes in the
      C/N imbalance of the plant. N starved mycorrhizal plants showed lower C/N
      equilibrium in the shoots than starved NM plants and concomitantly a
      downregulation of the JAZ1 repressor and the increased expression of the DELLA
      gene, which translated into a more active oxylipin pathway in mycorrhizal plants.
      In addition, the results support a priorization in AM plants of stress responses
      over growth. Therefore, these plants were better prepared for an expected stress.
      Furthermore, most metabolites that were severely reduced in NM plants following
      the N depletion remained unaltered in starved AM plants compared with those
      normally fertilized, suggesting that the symbiosis buffered the stress, improving
      plant development in a stressed environment.

PMID- 29194659
TI  - A stress-associated protein, AtSAP13, from Arabidopsis thaliana provides
      tolerance to multiple abiotic stresses.
AB  - Members of Stress-Associated Protein (SAP) family in plants have been shown to
      impart tolerance to multiple abiotic stresses, however, their mode of action in
      providing tolerance to multiple abiotic stresses is largely unknown. There are 14
      SAP genes in Arabidopsis thaliana containing A20, AN1, and Cys2-His2 zinc finger
      domains. AtSAP13, a member of the SAP family, carries two AN1 zinc finger domains
      and an additional Cys2-His2 domain. AtSAP13 transcripts showed upregulation in
      response to Cd, ABA, and salt stresses. AtSAP13 overexpression lines showed
      strong tolerance to toxic metals (AsIII, Cd, and Zn), drought, and salt stress.
      Further, transgenic lines accumulated significantly higher amounts of Zn, but
      less As and Cd accumulation in shoots and roots. AtSAP13 promoter-GUS fusion
      studies showed GUS expression predominantly in the vascular tissue, hydathodes,
      and the apical meristem and region of root maturation and elongation as well as
      the root hairs. At the subcellular level, the AtSAP13-eGFP fusion protein was
      found to localize in both nucleus and cytoplasm. Through yeast one-hybrid assay,
      we identified several AP2/EREBP family transcription factors that interacted with
      the AtSAP13 promoter. AtSAP13 and its homologues will be highly useful for
      developing climate resilient crops.

PMID- 29194661
TI  - Solar UV-B radiation and ethylene play a key role in modulating effective
      defenses against Anticarsia gemmatalis larvae in field-grown soybean.
AB  - Solar UV-B radiation has been reported to enhance plant defenses against
      herbivore insects in many species. However, the mechanism and traits involved in
      the UV-B mediated increment of plant resistance are unknown in crops species,
      such as soybean. Here, we studied defense-related responses in undamaged and
      Anticarsia gemmatalis larvae-damaged leaves of two soybean cultivars grown under
      attenuated or full solar UV-B radiation. We determined changes in jasmonates,
      ethylene (ET), salicylic acid, trypsin protease inhibitor activity, flavonoids,
      and mRNA expression of genes related with defenses. ET emission induced by
      Anticarsia gemmatalis damage was synergistically increased in plants grown under
      solar UV-B radiation and was positively correlated with malonyl genistin
      concentration, trypsin proteinase inhibitor activity and expression of IFS2, and
      the pathogenesis protein PR2, while was negatively correlated with leaf
      consumption. The precursor of ET, aminocyclopropane-carboxylic acid, applied
      exogenously to soybean was sufficient to strongly induce leaf isoflavonoids. Our
      results showed that in field-grown soybean isoflavonoids were regulated by both
      herbivory and solar UV-B inducible ET, whereas flavonols were regulated by solar
      UV-B radiation only and not by herbivory or ET. Our study suggests that, although
      ET can modulate UV-B-mediated priming of inducible plant defenses, some plant
      defenses, such as isoflavonoids, are regulated by ET alone.

PMID- 29194662
TI  - Quantitative Predictive Models for the Degree of Disability After Acute Ischemic
      Stroke.
AB  - Although stroke is a leading cause of disability, the quantitative relationship
      between baseline clinical and imaging characteristics and long-term disability
      outcomes has rarely been studied. Prospectively collected clinical data from 405
      patients with acute ischemic stroke including brain magnetic resonance images
      (MRIs) and disability outcomes assessed using the modified Rankin Scale (mRS) 3
      month after the onset of disease were analyzed using a proportional odds
      cumulative logit model implemented in NONMEM. The relationship between the
      difference in lesion volume (DLV) - lesion volume measured by brain MRI 5 days
      later - lesion volume at the onset of the disease, and the mRS measured at 3
      months (mRS3) was modeled first, and the potential covariates were tested. The
      Emax model best described the relationship between DLV and the logit probability
      of each mRS3. DLV, baseline stroke severity, age, and diabetes mellitus were
      identified as significant predictors of the probabilities of mRS3. The
      quantitative model constructed in the current analysis will enable us to predict
      the long-term disabilities of the patients with acute ischemic stroke using the
      patient-specific MRI and other clinical information, which will be useful for
      individualizing therapies and for making the clinical development of a novel drug
      more efficient.

PMID- 29194660
TI  - Dietary exposure assessment of cyadox based on tissue depletion of cyadox and its
      major metabolites in pigs, chickens, and carp.
AB  - The tissue kinetics of cyadox, an antibacterial agent used in food animals, and
      its major metabolites in pigs, chickens, and carp were investigated followed by a
      complete dietary exposure assessment to evaluate the food safety of cyadox.
      Cyadox and its major metabolites, bisdeoxycyadox (Cy1), 4-desoxycyadox (Cy2), N
      (quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), quinoxaline-2-carboxylic
      acid (Cy6), and 2-hydromethyl-3-hydroxy-quinoxaline (Cy12), were simultaneously
      quantitated with a high-performance liquid chromatography-ultraviolet (HPLC-UV)
      method. Pigs, chickens, and carp were fed with 150 mg/kg cyadox in feed for
      consecutive 60, 40, and 30 days, respectively. The residue amount of cyadox and
      its major metabolites in liver, kidney, muscle, and fat (skin) tissues was
      determined. Cy2 was below the limit of quantitation even at the withdrawal time
      of 6 hr, cyadox, Cy4, Cy6, and Cy12 could be detected at 6-24 hr with low level
      less than 50 MUg/kg. By contrast, Cy1 persisted for 3 days in the kidney of pigs
      and chickens, and in the liver of carp. Based on these residue depletion data and
      previous toxicology results, the global estimated chronic dietary exposure
      assessment of cyadox for general population was conducted, indicating a zero
      withdrawal time (WDT) may be appropriate for cyadox in food animals when used in
      feed for prolonged administration. These results provide analytical techniques
      and safety standards suitable for residue monitoring of cyadox in food animals.

PMID- 29194663
TI  - Nanoemulsion from essential oil of Pterodon emarginatus (Fabaceae) shows in vitro
      efficacy against monogeneans of Colossoma macropomum (Pisces: Serrasalmidae).
AB  - Outbreaks of diseases pose a major threat to sustainable aquaculture development
      worldwide. Application of herbal products to combat parasitic diseases provides
      an alternative approach for sustainable aquaculture. This study investigated the
      in vitro antiparasitic effects of an oil-in-water nanoemulsion prepared using the
      essential oil from Pterodon emarginatus, against monogeneans infesting Colossoma
      macropomum. Gill arches from C. macropomum (47.6 +/- 14.5 g and 13.5 +/- 1.4 cm)
      that were naturally parasitized by Anacanthorus spathulatus, Notozothecium
      janauachensis and Mymarothecium boegeri were immersed in different dispersions of
      the P. emarginatus nanoemulsions (0, 50, 100, 200, 400 and 600 mg/L). The major
      compounds presented in the essential oil of P. emarginatus were beta-elemene,
      beta-caryophyllene and alpha-humulene. Characterization of these nanoemulsions
      showed that they have a small mean droplet size and low polydispersity index,
      which is concordant with stable systems. In this in vitro trial, the P.
      emarginatus nanoemulsion concentrations of 100, 200, 400 and 600 mg/L presented
      100% helminthic efficacy against monogeneans of the gills of C. macropomum. The
      highest two concentrations used (400 and 600 mg/L) were seen to immobilize the
      parasites after only 15 min. Therefore, it would be worthwhile testing these
      concentrations in therapeutic baths against monogeneans of C. macropomum.

PMID- 29194664
TI  - The plant hormone salicylic acid interacts with the mechanism of anti-herbivory
      conferred by fungal endophytes in grasses.
AB  - The plant hormone salicylic acid (SA) is recognized as an effective defence
      against biotrophic pathogens, but its role as regulator of beneficial plant
      symbionts has received little attention. We studied the relationship between the
      SA hormone and leaf fungal endophytes on herbivore defences in symbiotic grasses.
      We hypothesize that the SA exposure suppresses the endophyte reducing the fungal
      produced alkaloids. Because of the role that alkaloids play in anti-herbivore
      defences, any reduction in their production should make host plants more
      susceptible to herbivores. Lolium multiflorum plants symbiotic and nonsymbiotic
      with the endophyte Epichloe occultans were exposed to SA followed by a challenge
      with the aphid Rhopalosiphum padi. We measured the level of plant resistance to
      aphids, and the defences conferred by endophytes and host plants. Symbiotic
      plants had lower concentrations of SA than did the nonsymbiotic counterparts.
      Consistent with our prediction, the hormonal treatment reduced the concentration
      of loline alkaloids (i.e., N-formyllolines and N-acetylnorlolines) and
      consequently decreased the endophyte-conferred resistance against aphids. Our
      study highlights the importance of the interaction between the plant immune
      system and endophytes for the stability of the defensive mutualism. Our results
      indicate that the SA plays a critical role in regulating the endophyte-conferred
      resistance against herbivores.

PMID- 29194665
TI  - Efficacy and safety of a new human fibrinogen concentrate in patients with
      congenital fibrinogen deficiency: an interim analysis of a Phase III trial.
AB  - BACKGROUND: Fibrinogen concentrate is the preferred choice for fibrinogen
      replacement in congenital fibrinogen deficiency. This study investigated
      hemostatic efficacy of a new plasma-derived, double virus-inactivated (using two
      dedicated virus inactivation/elimination steps) human fibrinogen concentrate for
      on-demand treatment of bleeding episodes (BEs) and surgical prophylaxis. STUDY
      DESIGN AND METHODS: In this planned interim analysis of a prospective,
      multinational Phase III study (NCT02267226), 13 patients with afibrinogenemia
      (>=12 years) received fibrinogen concentrate (FIBRYGA, Octapharma AG). Hemostatic
      efficacy was assessed by investigators and an independent data monitoring and
      endpoint adjudication committee (IDMEAC) using objective four-point criteria and
      by thromboelastometry maximum clot firmness (MCF). RESULTS: Fibrinogen
      concentrate was used on-demand to treat 23 BEs in 11 patients, with 21 (91.3%)
      requiring a single infusion only. Treatment success was 95.7% (90% confidence
      interval [CI], 0.81-1.00; assessment missing for one BE) by investigators and
      100% (90% CI, 0.88-1.00) by IDMEAC. Mean MCF increased significantly from 0.0 to
      6.5 mm (95% CI, 5.65-7.40; p < 0.0001) at 1 hour postinfusion of a median (range)
      dose of 58.8 (33.9-101.7) mg/kg per BE. Four patients received fibrinogen
      concentrate as surgical prophylaxis, with intraoperative and postoperative
      treatment success rated 100% (90% CI, 0.50-1.00) by investigators and IDMEAC
      (median [range] dose per surgery 93.5 [34.1-225.4] mg/kg). No additional
      hemostatic interventions were required. No deaths, thromboses, or seroconversions
      were reported. CONCLUSION: These data showed that the new fibrinogen concentrate
      was efficacious for on-demand treatment of acute bleeding and surgical
      prophylaxis in congenital afibrinogenemia patients.

PMID- 29194666
TI  - Feasibility of Implementation of a Parenting Intervention with Karen Refugees
      Resettled from Burma.
AB  - Parents and children exposed to war and relocation have high rates of negative
      relational and mental health outcomes. This study tested the feasibility of
      implementing an adapted evidence-based parenting intervention for contexts of
      trauma and relocation stress. Eleven Karen refugee caregivers from Burma
      participated in the intervention. Participants and a focal child completed
      ethnographic interviews as well as structured assessments at baseline and follow
      up. Caregivers reported changes in their teaching, directions, emotional
      regulation, discipline, and child compliance. Children reported changes in these
      areas and in positive parent involvement. Caregivers reported higher mental
      health distress immediately after the intervention, potentially due to increased
      awareness. Researchers made personalized referrals for counseling services as
      needed. Children reported a decrease in mental health symptoms.

PMID- 29194667
TI  - Evaluation of the impact of banking umbilical cord blood units with high cell
      dose for ethnically diverse patients.
AB  - BACKGROUND: Umbilical cord blood units provide an important stem cell source for
      transplantation, particularly for patients of ethnic diversity who may not have
      suitably matched available, adult-unrelated donors. However, with the cost of
      cord blood unit acquisition from public banks significantly higher than that for
      adult-unrelated donors, attention is focused on decreasing cost yet still
      providing cord blood units to patients in need. Historical practices of banking
      units with low total nucleated cell counts, including units with approximately 90
      * 107 total nucleated cells, indicates that most banked cord blood units have
      much lower total nucleated cell counts than are required for transplant. STUDY
      DESIGN AND METHODS: The objective of this study was to determine the impact on
      the ability to identify suitable cord blood units for transplantation if the
      minimum total nucleated cell count for banking were increased from 90 * 107 to
      124 or 149 * 107 . We analyzed ethnically diverse patients (median age, 3 years)
      who underwent transplantation of a single cord blood unit in 2005 to 2016. A cord
      blood unit search was evaluated to identify units with equal or greater human
      leukocyte antigen matching and a greater total nucleated cell count than that of
      the transplanted cord blood unit (the replacement cord blood unit). RESULTS: If
      the minimum total nucleated cell count for banking increased to 124 or 149 * 107
      , then from 75 to 80% of patients would still have at least 1 replacement cord
      blood unit in the current (2016) cord blood unit inventory. The best replacement
      cord blood units were often found among cords with the same ethnic background as
      the patient. CONCLUSION: The current data suggest that, if the minimum total
      nucleated cell count were increased for banking, then it would likely lead to an
      inventory of more desirable cord blood units while having minimal impact on the
      identification of suitable cord blood units for transplantation.

PMID- 29194668
TI  - Is an endoscopic examination associated with transfusion-transmissible
      infections? A systematic review and meta-analysis.
AB  - BACKGROUND: The purpose of a donor medical questionnaire is to identify the blood
      donor's history relative to the current known blood-safety risks. A temporary
      deferral from blood donation after an endoscopic examination is enforced because
      of the reusable nature of the endoscope and close contact with the inner body.
      The objective of this systematic review was to find the best available evidence
      on the association between an endoscopic examination and the risk of transfusion
      transmissible infections. METHODS: Studies from five databases investigating the
      link between an endoscopic examination and transfusion-transmissible infections
      (hepatitis B virus, hepatitis C virus, human immunodeficiency virus infection,
      Treponema pallidum) were retained and assessed independently by two reviewers.
      The association between endoscopy and transfusion-transmissible infections was
      identified by conducting meta-analyses and calculating pooled effect measures
      (odds ratios and 95% confidence intervals). The Grading of Recommendations,
      Assessment, Development, and Evaluation methodology was used to assess the
      quality of evidence. RESULTS: We identified 7571 references and finally included
      29 observational studies. A significant association between an endoscopic
      examination and hepatitis B virus infection (pooled odds ratio [OR], 2.21; 95%
      confidence interval [CI], 1.26-3.86; p = 0.005) or hepatitis C virus infection
      (pooled OR 1.76, 95% CI, 1.45-2.14; p < 0.00001) was found. The level of evidence
      was considered as "very low" due to the type of study design (i.e.,
      observational) and indirect study populations (i.e., no blood donor populations).
      CONCLUSION: An endoscopic examination is associated with an increased hepatitis B
      virus or hepatitis C virus infection risk. Further high-quality trials are
      required to formulate stronger evidence-based recommendations on endoscopic
      examination as a blood donor deferral criterion.

PMID- 29194669
TI  - Red blood cell transfusion in adult palliative care: a systematic review.
AB  - BACKGROUND: The risks and benefits of red blood cell (RBC) transfusion in
      palliative care patients remain poorly understood. We reviewed the literature to
      summarize available information on RBC transfusion in this population. STUDY
      DESIGN AND METHODS: We searched electronic databases (MEDLINE, Embase, PsycINFO,
      CINAHL) from inception through September 2016 to identify studies reporting data
      on palliative patients receiving RBC transfusion. Original studies that assessed
      RBC transfusion as an intervention and reported at least one clinical outcome
      were included. Study characteristics, results on transfusion-related outcomes,
      and authors' conclusions on the value of transfusion in palliative patients were
      abstracted and reported. RESULTS: We identified 1839 studies, of which 137 were
      selected for data extraction and 13 were included (11 case series, one
      prospective cohort, and one retrospective cohort). Nine studies addressed symptom
      relief following transfusion using subjective symptom scales, of which eight
      (89%) indicated some degree of short-term benefit and one study (11%) showed no
      benefit. Posttransfusion survival was reported in four studies-one demonstrated
      prolonged survival in patients receiving RBC transfusion; three had no comparison
      group. Other outcomes reported included hemoglobin values posttransfusion in four
      studies and adverse events following transfusion in three studies. CONCLUSIONS:
      In palliative care, RBC transfusion may provide symptom relief and improve
      subjective well-being, though the duration and magnitude of this effect, and
      transfusion-associated risks specific to this population remain unclear.
      Currently, no high quality evidence exists to support or guide the use of RBC
      transfusion in this population. Moreover, the clinical heterogeneity within the
      palliative population limits the interpretation of most studies.

PMID- 29194670
TI  - Endoscopic and surgical removal of oesophageal and gastric fishhook foreign
      bodies in 33 animals.
AB  - OBJECTIVES: To describe the location, retrieval, frequency of surgery and
      complications associated with fishhook foreign bodies. MATERIALS AND METHODS:
      Retrospective evaluation of the medical records of cats and dogs admitted between
      2010 and 2016 after fishhook ingestion. RESULTS: A total of 33 cases (2 cats and
      31 dogs) were included. The most common locations were the proximal oesophagus
      [12/33 (36%)] and stomach [11/33 (33%)]. Endoscopic retrieval was successful in
      27 of 33 cases (82%); oesophageal perforation was the only recorded complication,
      occurring in six of 33 (18%) cases. Surgery was performed in six cases (18%), and
      no early complications were recorded. The survival rate was 100%. CLINICAL
      SIGNIFICANCE: The endoscopic removal of ingested fishhooks is highly successful.
      In the present study, survival to discharge was 100%, even in cases of
      oesophageal perforation or in cases requiring surgery.

PMID- 29194671
TI  - Chronic hepatitis E in patients with indolent lymphoma after treatment with
      rituximab and bendamustine.

PMID- 29194672
TI  - Letter response: Reporting of mitotic rate in cutaneous melanoma.

PMID- 29194673
TI  - Transected thin melanoma: Implications for sentinel lymph node staging.
AB  - BACKGROUND AND OBJECTIVES: Indications for sentinel lymph node (SLN) biopsy in
      patients with thin melanoma (<=1 mm thick) are controversial. We asked whether
      deep margin (DM) positivity at initial biopsy of thin melanoma is associated with
      SLN positivity. METHODS: Cases were identified using prospectively maintained
      databases at two melanoma centers. Patients who had undergone SLN biopsy for
      melanoma <=1 mm were included. DM status was assessed for association with SLN
      metastasis in univariate and multivariate analyses. RESULTS: 1413 cases were
      identified, but only 1129 with known DM status were included. 39% of patients had
      a positive DM on original biopsy. DM-positive and DM-negative patients did not
      differ significantly in primary thickness, ulceration, or mitotic activity. DM
      positive and DM-negative patients had similar incidence of SLN metastasis (5.7%
      vs 3.5%; P = 0.07). Positive DM was not associated with SLN metastasis on
      univariate analysis (OR 1.69, 95% CI: 0.95-3.00, P = 0.07) or on multivariate
      analysis adjusted for Breslow depth, Clark level, mitotic rate, and ulceration
      (OR = 1.59, 95% CI: 0.89-2.85; P = 0.12). CONCLUSIONS: For patients with thin
      melanoma, a positive DM on initial biopsy is not associated with risk of SLN
      metastasis, so DM positivity should not be considered an indication for SLN
      staging in an otherwise low-risk patient.

PMID- 29194674
TI  - A whole genome sequence association study for puberty in a large Duroc *
      Erhualian F2 population.
AB  - A large proportion of gilts and sows are culled from reproduction populations
      because of anestrus and pubertal reproductive failure. Selecting early onset of
      puberty gilts has a favorable effect on sows' reproductivity. However, age at
      puberty is hard to be routinely measured in commercial herds. With molecular
      genetic predictors, identifying individuals that have a propensity for early
      onset of puberty can be simplified. We previously performed genome scanning and a
      genome-wide association study for puberty in an F2 resource population using 183
      microsatellites and 62 125 SNPs respectively. The detection power and resolution
      of identified quantitative trait loci were very low. Herein, we re-sequenced 19
      founders of the F2 resource population in high coverage, and whole genome
      sequences of F2 individuals were imputed to perform an association study for
      reproductive traits. A total of 2339 SNPs associated with pubertal reproductive
      failure were identified in the region of 30.94-40.74 Mb on SSC7, with the top
      one, positioned at 33.36 Mb, explaining 16% of the phenotypic variances. We
      improved the magnitude of the P-value by 10E+5 to 10E+7 using the whole genome
      sequence rather than using low/middle density markers as in previous studies, and
      we narrowed down the QTL confidence interval to 5.25 Mb. Combining the annotation
      of gene function, RAB23 and BAK1 were perceived as the most compelling candidate
      genes. The identified loci may be useful in culling sows failing to show estrus
      by marker-assisted selection to increase reproductive efficiency of swine herds.

PMID- 29194675
TI  - Peacekeepers are cross-dressed in the liver land.

PMID- 29194676
TI  - Extremely high-frequency electromagnetic radiation enhances neutrophil response
      to particulate agonists.
AB  - The growing use of extremely high-frequency electromagnetic radiation (EHF EMR)
      in information and communication technology and in biomedical applications has
      raised concerns regarding the potential biological impact of millimeter waves
      (MMWs). Here, we elucidated the effects of MMW radiation on neutrophil activation
      induced by opsonized zymosan or E. coli in whole blood ex vivo. After agonist
      addition to blood, two samples were prepared. A control sample was incubated at
      ambient conditions without any treatment, and a test sample was exposed to EHF
      EMR (32.9-39.6 GHz, 100 W/m2 ). We used methods that allowed us to assess the
      functional status of neutrophils immediately after exposure: oxidant production
      levels were measured by luminol-dependent chemiluminescence, and morphofunctional
      changes to neutrophils were observed in blood smears. Results revealed that the
      response of neutrophils to both agonists was intensified if blood was exposed to
      MMW radiation for 15 min. Neutrophils were intact in both the control and
      irradiated samples if no agonist was added to blood before incubation. Similarly,
      exposing suspensions of isolated neutrophils in plasma to MMW radiation enhanced
      cell response to both zymosan and E. coli. Heating blood samples was shown to be
      the primary mechanism underlying enhanced EHF EMR-induced oxidant production by
      neutrophils in response to particulate agonists. Bioelectromagnetics. 39:144-155,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29194677
TI  - Chronic inflammatory demyelinating polyneuropathy and malignancy: A systematic
      review.
AB  - A systematic review of the literature was performed on the association of chronic
      inflammatory demyelinating polyneuropathy (CIDP) with malignancy. Hematological
      disorders are the most common association, particulalry non-Hodgkin lymphoma.
      CIDP frequently precedes the malignancy diagnosis, and there is a favorable CIDP
      response to treatment more than 70% of the time. Melanoma is the second most
      common association and may be accompanied by antiganglioside antibodies; CIDP
      shows a good response to immunotherapy. Other cancers are rare, with variable
      timings and presentations but good responses to immunomodulation and/or cancer
      therapy. Unusual neurological features such as ataxia, distal/upper limb
      predominance, or cranial/respiratory/autonomic involvement may suggest associated
      malignancy as may abdominal pain, diarrhea/constipation, poor appetite/weight
      loss, dermatological lesions, and lymphadenopathy. In the appropriate clinical
      and electrophysiological setting, CIDP associated with cancer should be
      considered. Immunomodulatory therapy, cancer treatment alone, or a combination
      may be effective. Muscle Nerve 57: 875-883, 2018.

PMID- 29194679
TI  - Bringing the cell nucleus in the focus of NAFLD.

PMID- 29194678
TI  - Bleeding complications in acute liver failure.
AB  - : In patients with acute liver failure (ALF), elevated prothrombin time and
      thrombocytopenia can fuel a perception of a bleeding tendency. However, the
      incidence, site, risk factors, and clinical significance of bleeding
      complications have not been quantified in a large cohort of patients with ALF. We
      studied 1,770 adult patients enrolled in the ALF Study Group Registry between
      1998 and 2016. Bleeding complications and blood component transfusions were
      collected for 7 days after admission. The relationship of bleeding complications
      to 21-day mortality was assessed. Despite a median international normalized ratio
      of 2.7 and platelet count of 96 * 109 /L on admission, bleeding complications
      were observed in only 187 patients (11%), including 173 spontaneous and 22
      postprocedural bleeding episodes. Eighty-four percent of spontaneous bleeding
      episodes were from an upper gastrointestinal source and rarely resulted in red
      blood cell transfusion. Twenty patients experienced an intracranial bleed; half
      of these occurred spontaneously and half after intracranial pressure monitor
      placement, and this was the proximate cause of death in 20% and 50%,
      respectively. Bleeders and patients who received red blood cell transfusions were
      more acutely ill from extrahepatic organ system failure but not from
      hepatocellular failure. Consistent with this observation, bleeding complications
      were associated with lower platelet counts but not higher international
      normalized ratio. Transfusion of any blood component was associated with nearly 2
      fold increased death or need for liver transplantation at day 21, but bleeding
      complications were the proximate cause of death in only 5% of cases. CONCLUSIONS:
      Despite a perceived bleeding diathesis, clinically significant bleeding is
      uncommon in patients with ALF; bleeding complications in patients with ALF are
      markers of severe systemic inflammation rather than of coagulopathy and so
      portend a poor prognosis. (Hepatology 2018;67:1931-1942).

PMID- 29194680
TI  - Who gets the gametes? An argument for a points system for fertility patients.
AB  - This paper argues that the convention of allocating donated gametes on a 'first
      come, first served' basis should be replaced with an allocation system that takes
      into account more morally relevant criteria than waiting time. This conclusion
      was developed using an empirical bioethics methodology, which involved a study of
      the views of 18 staff members from seven U.K. fertility clinics, and 20
      academics, policy-makers, representatives of patient groups, and other relevant
      professionals, on the allocation of donated sperm and eggs. Against these views,
      we consider some nuanced ways of including criteria in a points allocation
      system. We argue that such a system is more ethically robust than 'first come,
      first served', but we acknowledge that our results suggest that a points system
      will meet with resistance from those working in the field. We conclude that
      criteria such as a patient's age, potentially damaging substance use, and
      parental status should be used to allocate points and determine which patients
      receive treatment and in what order. These and other factors should be applied
      according to how they bear on considerations like child welfare, patient welfare,
      and the effectiveness of the proposed treatment.

PMID- 29194682
TI  - Impact of hepatitis C virus polymorphisms on direct-acting antiviral treatment
      efficacy: Regulatory analyses and perspectives.
AB  - : Several highly effective, interferon-free, direct-acting antiviral (DAA)-based
      regimens are available for the treatment of chronic hepatitis C virus (HCV)
      infection. Despite impressive efficacy overall, a small proportion of patients in
      registrational trials experienced treatment failure, which in some cases was
      associated with the detection of HCV resistance-associated substitutions (RASs)
      at baseline. In this article, we describe methods and key findings from
      independent regulatory analyses investigating the impact of baseline
      nonstructural (NS) 3 Q80K and NS5A RASs on the efficacy of current United States
      Food and Drug Administration (FDA)-approved regimens for patients with HCV
      genotype (GT) 1 or GT3 infection. These analyses focused on clinical trials that
      included patients who were previously naive to the DAA class(es) in their
      investigational regimen and characterized the impact of baseline RASs that were
      enriched in the viral population as natural or transmitted polymorphisms (i.e.,
      not drug-selected RASs). We used a consistent approach to optimize comparability
      of results across different DAA regimens and patient populations, including the
      use of a 15% sensitivity cutoff for next-generation sequencing results and
      standardized lists of NS5A RASs. These analyses confirmed that detection of NS3
      Q80K or NS5A baseline RASs was associated with reduced treatment efficacy for
      multiple DAA regimens, but their impact was often minimized with the use of an
      intensified treatment regimen, such as a longer treatment duration and/or
      addition of ribavirin. We discuss the drug resistance-related considerations that
      contributed to pretreatment resistance testing and treatment recommendations in
      drug labeling for FDA-approved DAA regimens. CONCLUSION: Independent regulatory
      analyses confirmed that baseline HCV RASs can reduce the efficacy of certain DAA
      based regimens in selected patient groups. However, highly effective treatment
      options are available for patients with or without baseline RASs. (Hepatology
      2018;67:2430-2448).

PMID- 29194683
TI  - Leadless pacemaker extraction from a single-center perspective.
AB  - BACKGROUND: Leadless pacemaker can be considered as a technical revolution in
      cardiac pacing devices, with clear advantages over conventional pacemakers in
      overcoming all lead-related complications. However, the management of these
      devices once they reach the end of life (EOL) of the battery is still
      controversial. In the next years, there will be an increase in the need to define
      a clear strategy in the management of leadless PM once they reach their EOL. Safe
      extraction of these devices will define in a great manner this strategy METHODS:
      We performed the extraction of three functioning Nanostim leadless pacemaker
      prophylactically in two females and one male patients as part of the Nanostim
      battery depletion field action recommendation. All patients had a prior
      transesophageal 3D echocardiography to determine the device intracardiac mobility
      and the extent of possible endothelialization. For the extractions, we used the
      Nanostim Retrieval Catheter S1RSIN (St. Jude Medical, St. Paul, MN, USA), which
      is a proprietary catheter provided by the manufacturing company based on a lasso.
      RESULTS: Complete extraction of the devices was achieved in all patients using a
      relatively short fluoroscopic time (16, 19, and 12 minutes). CONCLUSIONS: The
      extraction of leadless pacemakers can be considered as a safe and feasible
      procedure using the tools provided by the manufacturer and designed for the
      extraction. However, a very low threshold must be maintained to avoid any risk to
      the patients. Our extraction time ranges are between 983 and 1,070 days,
      nevertheless it is necessary to gather more long-term data to assess the
      feasibility and safety of these procedures.

PMID- 29194681
TI  - A Population-based Study of Perinatal Infection Risk in Women with and without
      Systemic Lupus Erythematosus and their Infants.
AB  - BACKGROUND: Increased risk of adverse birth outcomes is well described in women
      with systemic lupus erythematosus (SLE), but risk of maternal or infant infection
      in the peripartum period has not been well studied. We conducted a population
      based cohort study of infection risk in women with and without SLE and their
      infants. METHODS: Linked birth-hospital discharge data identified 1297 deliveries
      to women with SLE and a 4:1 comparison cohort of deliveries to women without SLE
      in Washington State, 1987-2013. Maternal and infant infections during the first
      30 days after delivery were identified. Relative risks (RR) and 95% confidence
      intervals (CI) were estimated. RESULTS: Women with SLE were 1.7 times more likely
      (95% CI 1.4, 2.0) to have an infection during the birth hospitalisation and more
      likely to receive antibiotics during labour (RR 1.3, 95% CI 1.1, 1.5), though
      there was no increased risk of chorioamnionitis in women with SLE. Infants of
      women with SLE had an increased risk for an infection during the birth
      hospitalisation (RR 2.2, 95% CI 1.3, 3.5), although the size of the difference
      was smaller when adjusted for gestational age (RR 1.4, 95% CI 0.9, 2.1). Risks of
      neonatal infection, sepsis, receipt of antibiotics, and admission to neonatal
      intensive care were also increased, and were also attenuated after adjustment for
      gestational age. CONCLUSIONS: Women with SLE have an increased risk of peripartum
      infections and antibiotic exposure. Their neonates have a greater likelihood of
      infection, much of which is attributable to preterm birth.

PMID- 29194684
TI  - Global microRNA expression profiling in the liver biopsies of hepatitis B virus
      infected patients suggests specific microRNA signatures for viral persistence and
      hepatocellular injury.
AB  - : Hepatitis B virus (HBV) can manipulate the microRNA (miRNA) regulatory networks
      in infected cells to create a permissive environment for viral replication,
      cellular injury, disease onset, and its progression. The aim of the present study
      was to understand the miRNA networks and their target genes in the liver of
      hepatitis B patients involved in HBV replication, liver injury, and liver
      fibrosis. We investigated differentially expressed miRNAs by microarray in liver
      biopsy samples from different stages of HBV infection and liver disease (immune
      tolerant [n = 8], acute viral hepatitis [n = 8], no fibrosis [n = 16], early
      [F1+F2, n = 19] or late [F3+F4, n = 14] fibrosis, and healthy controls [n = 7]).
      miRNA expression levels were analyzed by unsupervised principal component
      analysis and hierarchical clustering. Analysis of miRNA-mRNA regulatory networks
      identified 17 miRNAs and 18 target gene interactions with four distinct nodes,
      each representing a stage-specific gene regulation during disease progression.
      The immune-tolerant group showed elevated miR-199a-5p, miR-221-3p, and Let-7a-3p
      levels, which could target genes involved in innate immune response and viral
      replication. In the acute viral hepatitis group, miR-125b-5p and miR-3613-3p were
      up, whereas miR-940 was down, which might affect cell proliferation through the
      signal transducer and activator of transcription 3 pathway. In early fibrosis,
      miR-34b-3p, miR-1224-3p, and miR-1227-3p were up, while miR-499a-5p was down,
      which together possibly mediate chronic inflammation. In advanced fibrosis, miR
      1, miR-10b-5p, miR-96-5p, miR-133b, and miR-671-5p were up, while miR-20b-5p and
      miR-455-3p were down, possibly allowing chronic disease progression.
      Interestingly, only 8 of 17 liver-specific miRNAs exhibited a similar expression
      pattern in patient sera. CONCLUSION: miRNA signatures identified in this study
      corroborate previous findings and provide fresh insight into the understanding of
      HBV-associated liver diseases which may be helpful in developing early-stage
      disease diagnostics and targeted therapeutics. (Hepatology 2018;67:1695-1709).

PMID- 29194685
TI  - Checkpoint modulation in chronic hepatitis B: From hypothesis to approval.

PMID- 29194686
TI  - New insights into the role and mechanism of c-Jun-N-terminal kinase signaling in
      the pathobiology of liver diseases.
AB  - The c-Jun-N-terminal-kinase (JNK) family is highly conserved across species such
      as Drosophila, C. elegans, zebrafish and mammals, and plays a central role in
      hepatic physiologic and pathophysiologic responses. These responses range from
      cell death to cell proliferation and carcinogenesis, as well as metabolism and
      survival, depending on the specific context and duration of activation of the JNK
      signaling pathway. Recently, several investigators identified the key molecules
      in the JNK activation loop which include apoptosis signal-regulating kinase
      (ASK1) and SH3-domain binding protein 5 (Sab) and their involvement in acute or
      chronic liver disease models. Thus, regulating JNK activation through modulating
      the JNK activation loop may represent an important new strategy in the prevention
      and treatment of acute and chronic liver diseases. In this review, we will
      discuss the molecular pathophysiology of the JNK activation loop and its role in
      the pathogenesis of liver diseases. (Hepatology 2018;67:2013-2024).

PMID- 29194687
TI  - Serum-free complete medium, an alternative medium to mimic androgen deprivation
      in human prostate cancer cell line models.
AB  - BACKGROUND: Almost all men who present with advanced prostate cancer (CaP) and
      some men who fail therapy for clinically localized CaP are treated with androgen
      deprivation therapy (ADT). CaP cell lines are used to identify and characterize
      new agents for ADT or investigate mechanisms of ADT resistance. CaP cell lines
      are maintained in culture medium that contains fetal bovine serum, which contains
      testosterone (T). Androgen deprivation experiments are performed using media
      supplemented with androgen-free serum, such as charcoal stripped fetal bovine
      serum (CS-FBS). However, CS-FBS composition varies from batch-to-batch and
      variations may impact experimental reproducibility. Serum free media (SFM) may
      provide a better defined alternative to media supplemented with CS-FBS (CSM).
      METHODS: Cell growth of six human CaP cell lines was assessed using 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Androgen levels were
      measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      RESULTS: MTT assays showed 5 of 6 CaP cell lines grew after 6 days of culture in
      androgen- deprived SFM or CSM. LNCaP and VCaP growth was stimulated when cells
      were cultured in SFM or CSM supplemented with T. LNCaP, C4-2, LAPC-4, and VCaP
      cell growth was inhibited when cultured in SFM or CSM with T and bicalutamide. LC
      MS/MS data showed LAPC-4 cells produced similar DHT levels when cultured in T
      supplemented SFM or CSM. Dutasteride impaired T to DHT metabolism in LAPC-4.
      CONCLUSIONS: Media composition contributed to growth differences observed between
      CaP cells cultured in SFM or CSM. However, the differences in media composition
      did not impair CaP cell response to T-stimulated growth, bicalutamide growth
      inhibition, metabolism of T, or dutasteride efficiency. SFM can be used as a
      better defined alternative to CSM for androgen deprivation experiments.

PMID- 29194688
TI  - The genetic diversity and population structures of indigenous pig breeds in
      Zhejiang Province revealed by GGRS sequencing.
AB  - Chinese indigenous pigs in Zhejiang Province are well known for their high
      fecundity. In order to verify breed subdivision at the genomic level, we
      investigated genetic diversity and population structure of seven breeds and made
      comparisons with three Western pig breeds using next-generation sequencing data.
      Parameters obtained from allelic richness and proportion of polymorphic markers
      indicated that the genetic diversity of the Chinese indigenous pigs was higher
      than that of the Western pigs, with the highest and lowest values found in the
      Chaluand and the Landrace pigs respectively. Both neighbor-joining tree and
      principal components analysis could distinguish breeds from one another and
      structure analysis showed less differentiation among Western pigs than among the
      Chinese pigs. The average linkage disequilibrium decay over distance was
      significantly less in the Chinese pigs compared with the Western pigs, ranging
      from 188.2 to 280.6 kb for the Chinese pigs and 680.3 to 752.8 kb for the Western
      breeds and showing an average r2 threshold value of 0.3. Results obtained from
      high-density SNP comparison over the whole genome on genetic diversity and
      population structure were in agreement with the current breed classification of
      the pigs in Zhejiang Province. More importantly, the results presented here
      advances our current understanding of the genomic biology of Chinese indigenous
      pigs in Zhejiang Province and allows for implementation of conservation
      strategies in additional breeds.

PMID- 29194689
TI  - New device for nonvolitional evaluation of quadriceps force in ventilated
      patients.
AB  - INTRODUCTION: In mechanically ventilated patients, nonvolitional assessment of
      quadriceps weakness using femoral-nerve stimulation (twitch force) while the leg
      rests on a right-angle trapezoid or dangles from the bed edge is impractical.
      Accordingly, we developed a knee-support apparatus for use in ventilated
      patients. METHODS: Ninety subjects (12 ventilated patients, 28 ambulatory
      patients, and 50 healthy subjects) were enrolled. Twitches with leg-dangling,
      trapezoid, and knee-support setups were compared. RESULTS: Knee-support twitches
      were similar to trapezoid twitches but smaller than leg-dangling twitches (P <
      0.0001). Inter- and intraoperator agreement was high for knee-support twitches at
      1 week and 1 month. In ventilated patients, knee-support twitches were smaller
      than in healthy subjects and ambulatory patients (P < 0.004). DISCUSSION: The new
      knee-support apparatus allows accurate recording of quadriceps twitches. The ease
      of use in ventilated patients and excellent inter- and intraoperator agreement
      suggest that this technique is suitable for cross-sectional and longitudinal
      studies in critically ill patients. Muscle Nerve 57: 784-791, 2018.

PMID- 29194690
TI  - A carbon 21 steroidal metabolite from progestin, 20beta-hydroxy-5alpha
      dihydroprogesterone, stimulates the androgen receptor in prostate cancer cells.
AB  - BACKGROUND: Clarifying the mechanisms underlying prostate cancer (PC) progression
      and resistance to androgen deprivation therapy (ADT) is an urgent clinical issue.
      ADT influences steroidal metabolism in patients with PC and promotes the
      accumulation of carbon 21 steroids (C21s), such as progestin. Because the enzymes
      responsible for C21s metabolism are similar to those for androgen metabolism, PC
      cells may be able to metabolize C21s intracellularly. Therefore, there is a
      possibility that intracrine C21s are implicated in PC progression and resistance
      to ADT, and the influence of C21s on PC cells is yet to be elucidated. In the
      present study, we focused on 20beta-hydroxy-5alpha-dihydroprogesterone (20beta
      OHDHP), a C21s metabolized from progestin, and showed that 20beta-OHDHP is
      synthesized in PC cells and is able to directly stimulate the androgen receptor
      (AR). METHODS: LNCaP, VCaP, and DU145 cells, which express a mutant AR (mAR),
      wild-type AR (wAR), and glucocorticoid receptor (GR), respectively, were
      incubated in the presence of several agents. After incubation, cell growth was
      determined by the MTS assay. PSA levels were determined by an enzyme immunoassay,
      and C21s and androgen levels were measured using liquid chromatography-mass
      spectrometry. Gene expression was analyzed by quantitative real-time polymerase
      chain reaction, and steroidal-receptor-related signaling was determined by a
      reporter assay. RESULTS: We affirmed that 20beta-OHDHP was synthesized from
      pregnenolone intracellularly in LNCaP and VCaP cells, and 20beta-OHDHP
      significantly promoted the growth of both cell lines without androgen conversion.
      20beta-OHDHP directly stimulated both mAR and wAR. The presence of 20beta-OHDHP
      was sufficient for the proliferation and survival of LNCaP or VCaP cells, and
      20beta-OHDHP promoted cell growth even in the presence of abiraterone. Using
      DU145 cells, we affirmed that 20beta-OHDHP did not stimulate GR, which has a
      potential to bypass AR signaling in PC cells promote PC cell growth. CONCLUSIONS:
      Under ADT, 20beta-OHDHP synthesized intracellularly from accumulated progestin in
      PC cells may accelerate cell growth via stimulation of both wAR and mAR. This
      pathway may represent an interesting candidate for targeted therapy.

PMID- 29194692
TI  - From Private Practice to Academia: Integrating social and political advocacy into
      every MFT Identity.
AB  - While advocacy was essential to establishing the field of marriage and family
      therapy, at present a social and political advocacy skill set is lacking for the
      typical marriage and family therapist (MFT). This article reviews the importance
      of being active in social and political advocacy and highlights the attributes of
      MFTs' professional identity that uniquely position us for success in these areas.
      Other mental health fields' pedagogical approaches to training and education are
      explored, and recommendations are made for how MFTs can begin to increase their
      competency in advocacy. Ideas for incorporating advocacy into a professional
      identity are presented for MFTs at every level of professional experience.
      Finally, the concept self-of-the-advocate is introduced and discussed.

PMID- 29194691
TI  - Mediterranean diet after prostate cancer diagnosis and urinary and sexual
      functioning: The health professionals follow-up study.
AB  - BACKGROUND: Men with prostate cancer often experience urinary and sexual
      dysfunction after treatment. Previous studies have demonstrated a relationship
      between dietary factors and these symptoms among men with diabetes or metabolic
      syndrome. However, there are limited data on whether diet after prostate cancer
      diagnosis, including a Mediterranean dietary pattern, affects urinary and sexual
      function among prostate cancer survivors. METHODS: Men diagnosed with non
      metastatic prostate cancer in the Health Professionals Follow-up Study (n = 2960)
      from 1986 to 2012 were prospectively followed for a median of 8.3 years after
      treatment. Participants completed validated dietary questionnaires every 4 years
      and a health-related quality of life assessment in 2010 or 2012. We used
      generalized linear models to examine associations between post-diagnosis
      Mediterranean Diet Score (including individual score components and dietary fat
      subtypes) and quality of life domains (sexual functioning, urinary
      irritation/obstruction, urinary incontinence) assessed using the Expanded
      Prostate Cancer Index Composite Short Form (score 0-100; higher scores indicate
      better function). RESULTS: No statistically significant relationships were
      observed between the Mediterranean Diet Score after prostate cancer diagnosis and
      urinary or sexual function. However, the associations did vary depending on pre
      diagnosis urinary and sexual dysfunction for urinary irritation/obstruction and
      sexual function scores, respectively (P-interactions < 0.0001). Men with higher
      post-diagnosis vegetable intake reported higher urinary incontinence scores (72
      vs 76 comparing lowest to highest quintile; P-trend = 0.003). Similarly, higher
      vegetable intake and lower polyunsaturated fat intake were associated with higher
      urinary irritation/obstruction scores (vegetable: 80 vs 84 comparing lowest to
      highest quintile, P-trend = 0.01; polyunsaturated fat: 84 vs 78 comparing lowest
      to highest quintile, P-trend = 0.005), however these associations were observed
      only among men with urinary symptoms prior to their prostate cancer diagnosis.
      CONCLUSIONS: Among men with prostate cancer, diet intake after diagnosis was not
      significantly associated with urinary or sexual function, although some
      relationships appeared to differ among men with and without symptoms prior to
      their prostate cancer diagnosis. Higher vegetable intake and lower
      polyunsaturated fat intake after prostate cancer diagnosis may be associated with
      better urinary function. However, this analysis was exploratory, and further
      research is needed to better delineate these relationships and guide dietary
      recommendations for men with prostate cancer.

PMID- 29194693
TI  - The Development and Implementation of a Multi-Couple Therapy Model with Torture
      Survivors in the Democratic Republic of the Congo.
AB  - In this article, we present development and feasibility of implementation of a
      multi-couple group for use with torture-surviving couples. The model was
      developed in the Democratic Republic of the Congo in a community that experienced
      widespread torture during the wars from 1998 to 2004. The Torture-Surviving
      Couple Group model is a short-term intervention designed to use few human
      resources to address relational difficulties resulting from exposure to traumatic
      stressors. The model was guided by critical and feminist epistemologies and
      employed an ecological lens to incorporate neurobiology and attachment processes
      along with narrative therapy techniques. An existing multi-couple group model for
      addressing violence (Stith, Rosen, McCollum, & Thomsen, ), and a stage model for
      healing trauma (Herman, ) also informed the structural development of the Torture
      Surviving Couple Group model. Couple groups were conducted using a 10-session
      program with 13 couples who met weekly. Session themes were incorporated into
      four phases emphasizing: (a) preparation; (b) safety and stabilization; (c)
      processing the relationship effects of trauma and grief; and (d) reintegration
      and rebuilding couple and family life. Couples reported and showed remarkable
      progress in their relationships after participating in the groups. Clinical and
      research implications and discussed along with the feasibility of developing and
      testing the model in a post-conflict low income setting.

PMID- 29194695
TI  - A Grounded Theory Study of How Couples Desist from Intimate Partner Violence.
AB  - Intimate partner violence is a common and damaging experience for many couples,
      and therapists struggle to address it adequately (Johnson, 2008). Despite its
      negative effects, many violent couples stay together, with some stopping their
      violent behaviors. Unfortunately, we know little about the systemic factors
      affecting violence desistance. This study used grounded theory methods to analyze
      the process of desistance in formerly violent couples. A model of desistance
      consisting of three categories was developed, which for most couples included a
      (a) Turning Point, (b) Decision to Change, and (c) Doing Things Differently.
      Therapists are encouraged to use the model to better understand the varied and
      systemic nature of violence and desistance, and to make more sophisticated
      decisions about referral and treatment.

PMID- 29194694
TI  - Hepatocellular carcinoma decreases the effectiveness of hepatitis C antiviral
      treatment: Do direct-acting antiviral regimens matter?

PMID- 29194696
TI  - Family Focused Care for Refugees and Displaced Populations: Global Opportunities
      for Family Therapists.
AB  - Recent global crises have created a significant increase in the number of people
      leaving their countries. Distress experienced by these refugees often leads to
      posttraumatic stress disorder and depression and can also result in psychotic
      disorders, substance abuse, and interpersonal violence. The World Health
      Organization leads the organizing of refugee services as part of a larger
      initiative to provide mental health services to citizens in low- and middle
      income countries. The World Health Organization has identified challenges in
      providing care, including a provider shortage, issues with how refugees access
      and receive care and a lack of uniformity in mental health services. By applying
      the values and systemic orientation of the profession, family therapists can
      address some of the challenges in treating mental health concerns of these at
      risk populations.

PMID- 29194697
TI  - Observed Interactions in Families of Adolescent Suicide Attempters.
AB  - Family interactions of 71 adolescents hospitalized following a suicide attempt
      were compared with those of 29 psychiatric controls, using observational methods
      and a 2-year prospective, longitudinal design. Parent-adolescent dyadic
      interactions were coded for emotional validation and invalidation, and problem
      solving constructiveness. There were no between-group differences for parents.
      However, adolescents who had attempted suicide displayed more emotional
      invalidation than controls. Within the suicide attempt group, maternal
      constructive problem solving predicted greater declines in youth suicide
      ideation, and a similar trend was observed for fathers. Adolescents who displayed
      more unconstructive problem solving with fathers were more likely to reattempt
      suicide during the follow up.

PMID- 29194698
TI  - Impaired Rivaroxaban Clearance in Mild Renal Insufficiency With Verapamil
      Coadministration: Potential Implications for Bleeding Risk and Dose Selection.
AB  - Pharmacokinetics and antithrombotic effects of the Factor Xa inhibitor
      rivaroxaban were studied in subjects with mild renal insufficiency concurrently
      taking the P-glycoprotein and moderate CYP3A inhibitor verapamil, a drug commonly
      administered to patients with hypertension, ischemic heart disease, or atrial
      fibrillation. Age-matched controls with normal renal function were studied
      concurrently. Subjects' overall mean age was 59 years. Mean creatinine clearance
      values in the 2 groups were 105 and 71 mL/min. After single 20-mg oral doses,
      rivaroxaban area under the curve (AUC) was increased by a factor of 1.11 (ratio
      of geometric means [RGM]) in mild renal insufficiency compared to controls.
      Verapamil coadministration independently increased AUC to the same extent in both
      the mild renal insufficiency and control groups (RGM, 1.39 and 1.43). Concurrent
      mild renal insufficiency and verapamil produced additive inhibition compared to
      controls without verapamil (RGM, 1.58). Prothrombin time (PT) prolongation and
      Factor Xa inhibition tracked plasma rivaroxaban, and were enhanced by verapamil.
      Concentration-response relationships for PT (linear) and Factor Xa inhibition
      (hyperbolic) were unaffected by renal function or verapamil. The absolute and
      relative increases in rivaroxaban AUC caused by verapamil in mild renal
      insufficiency subjects are potentially associated with an increased bleeding
      risk. Modification of recommended dosage may be required in this combination of
      circumstances to reduce risk to patients.

PMID- 29194699
TI  - Ultrasonographic Findings of 1385 Adrenal Masses: A Retrospective Study of 1319
      Benign and 66 Malignant Masses.
AB  - OBJECTIVES: To evaluate the features of adrenal masses on ultrasonography and
      correlate the findings with the pathologic diagnoses to help distinguish benign
      from malignant adrenal lesions. METHODS: Ultrasonography was performed in 1363
      patients with adrenal lesions. The following ultrasonographic parameters were
      recorded: size, shape, margin, echogenicity, echo texture, cystic necrosis,
      calcifications, and blood supply. The sensitivity and specificity of aggressive
      features for predicting malignancy were calculated. RESULTS: Of 1385 adrenal
      lesions, 66 (4.8%) were malignant: 33 malignant pheochromocytomas, 20 adrenal
      cortical carcinomas, 10 metastases, 2 leiomyosarcomas, and 1 primitive
      neuroectodermal tumor. The remaining 1319 (95.2%) lesions were benign: 832
      adenomas, 182 pheochromocytomas, 153 nodular adrenal hyperplasia, 54
      myelolipomas, 42 cysts, 23 ganglioneuromas, 10 schwannomas, 8 cortical tumor
      eosinophils, 4 teratomas, 4 tuberculosis, 4 primary pigmented nodular
      adrenocortical disease, and 3 Castleman disease. Most of the tumors were regular
      and hypoechoic. The malignant lesions were significantly larger than the benign
      lesions (mean +/- SD, 6.3 +/- 2.4 versus 4.6 +/- 1.7 cm; P < .01). Significant
      differences between malignant and benign tumors were observed when comparing the
      shape, margins, echo texture and vascularization of the analyzed lesions (P <
      .01). An irregular shape, poor definition of margins, heterogeneous echo texture,
      and vascularization indicated malignancy, with sensitivity and specificity of
      45.5% and 97.0%, 34.8% and 99.2%, 92.4% and 97.3%, and 15.2% and 97.5%,
      respectively. CONCLUSIONS: Ultrasonography could be an effective diagnostic
      supplementary tool for adrenal tumors. A large size, irregular shape, poorly
      defined margins, heterogeneous echo texture, and vascularization of adrenal
      lesions could be effective indicators of malignancy.

PMID- 29194700
TI  - Metastatic laryngeal large cell neuroendocrine carcinoma: A rare case of
      presentation and extreme tumor burden.
AB  - Large cell neuroendocrine carcinoma (LCNEC) of the larynx is an aggressive form
      of neuroendocrine carcinoma that affects smokers at an average age of 60 years.
      LCNEC is characterized by large cells with round to ovoid nuclei distributed in a
      trabecular or nested growth pattern. Previously, laryngeal LCNEC and atypical
      carcinoid tumors were considered identical; however, laryngeal LCNEC has been
      shown to have higher mitotic rates and worse prognosis, which has led to
      laryngeal LCNEC's being separated from atypical carcinoid and classified as a
      poorly differentiated neuroendocrine carcinoma in the most recent World Health
      Organization classification. We present a case of a 56-year-old female who
      presented with painful subcutaneous skin lesions that were diagnosed as
      metastatic carcinoma at an outside facility. Subsequent workup revealed a primary
      epiglottic lesion. Over the next 4 years, she continued to develop over 100
      similar subcutaneous nodules. Additional workup confirmed neuroendocrine
      differentiation, thus clarifying the diagnosis of metastatic LCNEC. Review of
      literature has revealed only 1 reported case of LCNEC with skin metastasis. This
      is the first reported case in which skin metastasis was the initial presenting
      symptom; moreover, our case is unique with regard to the heavy metastatic burden
      to the skin.

PMID- 29194701
TI  - Repeatability of Female Midurethral Measurement Using High-Frequency 3
      Dimensional Transvaginal Ultrasonography.
AB  - OBJECTIVES: Imaging assessment of the female urethra is critical for diagnosis
      and treatment of urinary incontinence. High-frequency 3-dimensional (3D)
      transvaginal ultrasonography (TVUS) is a novel technique for evaluating the
      female urethra. The aim of this study was to test the repeatability of 3D TVUS
      between examiners without prior experience with TVUS. METHODS: Fifty women
      underwent 3D TVUS. Two examiners without prior experience analyzed the urethral
      volumes and measured the urethral parameters. Two-dimensional (2D) parameters
      included urethral sphincter length and urethral sphincter thickness; 3D
      parameters included urethral sphincter volume, midurethral complex volume, and
      inner core volume. One of the examiners repeated the evaluations 1 month later.
      Subsequently, the measurements were compared. RESULTS: The mean age of the
      patients +/- SD was 34.1 +/- 8.1 (range, 23-55) years; the mean height, weight,
      and body mass index were 160.44 +/- 5.12 (range, 150-173) cm, 61.80 +/- 13.64
      (range, 45-110) kg, and 23.98 +/- 4.91 (range, 17.53-39.92) kg/m2 , respectively.
      The results of our study showed excellent to good intraobserver repeatability
      (intraclass correlation coefficient [ICC], 0.75-0.87) for the evaluations of all
      parameters but urethral sphincter length (moderate ICC, 0.53), whereas they
      showed good to moderate interobserver repeatability (ICC, 0.44-0.77) for all
      parameters. The repeatability of 3D volumes (ICC, 0.59-0.87) tended to be better
      than that of 2D parameters (ICC, 0.44-0.76). CONCLUSIONS: The intraobserver and
      interobserver repeatability of high-frequency 3D TVUS measurements of the female
      urethra was excellent to moderate between examiners without previous experience.
      The repeatability of 3D measurements tended to be better than that of 2D
      parameters.

PMID- 29194702
TI  - The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease.
AB  - We investigated the role of HFE C282Y, H63D, and TMPRSS6 A736V variants in the
      pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at
      diagnosis and after 1 year of gluten-free diet (GFD). Demographic and clinical
      features were prospectively recorded for all CD patients between 2013 and 2017.
      C282Y, H63D, and A736V variants were evaluated for CD patients and controls.
      Finally, 505 consecutive CD patients and 539 age-matched control subjects were
      enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of
      anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele
      frequency was significantly increased in CD compared with controls (1.1% vs 0.2%,
      P = .001), whereas H63D and A736V allele frequencies were similar among patients
      and controls (P = .92 and .84, respectively). At diagnosis, C282Y variant in
      anemic CD patients was significantly increased compared to nonanemic group (2%
      and 0.5%, P = .04). At follow-up, A736V was significantly increased in IDA
      persistent than in IDA not persistent (57.7% vs 35.2%, P < .0001). CD patients
      with H63D mutation showed higher Hb, MCV, serum iron, and ferritin levels than
      subjects without HFE mutations. Decreased hepcidin values were observed in anemic
      compared to nonanemic subjects at follow-up (1.22 +/- 1.14 vs 2.08 +/- 2.15, P <
      .001). This study suggests a protective role of HFE in IDA CD patients and
      confirms the role of TMPRSS6 in predicting oral iron response modulating hepcidin
      action on iron absorption. Iron supplementation therapeutic management in CD
      could depend on TMPRSS6 genotype that could predict persistent IDA despite iron
      supplementation and GFD.

PMID- 29194703
TI  - Development and psychometric evaluation of a rapid intimate partner violence
      perpetration screening tool.
AB  - Current methods of identifying intimate partner violence (IPV) perpetration rely
      upon lengthy screening instruments, partner injury, and legal involvement. There
      exist no viable, brief screening tools to facilitate the rapid and early
      identification of IPV perpetration. The development of a brief IPV screening tool
      would reduce participant burden and compensation in research as well as aid in
      self-identification and appropriate consultation for treatment. Three samples
      were recruited and administered an IPV assessment measure. Receiver Operating
      Characteristic (ROC) curve analyses were used to determine a critical subset of
      items that could be rapidly administered and used to accurately detect physical
      IPV perpetrators. A set of four items emerged that were capable of
      differentiating between partner violent and nonviolent participants in Samples 1
      (the Area Under the ROC Curve (AUC) = .95, SE = .02), 2 (AUC = .98, SE =.01), and
      3 (AUC = .94, SE = .04). Internal consistency of the screening items was
      acceptable across samples and the scores on the screening tool were significantly
      associated in the expected direction with all assessed risk factors for IPV.
      Initial evaluation of the rapid IPV perpetration screening tool suggests that it
      may help satisfy the growing need to quickly determine research eligibility and
      to help college students self-identify risk, offering objective data upon which
      to base the decision for follow-up consultation.

PMID- 29194704
TI  - Social play among juvenile wild Japanese macaques (Macaca fuscata) strengthens
      their social bonds.
AB  - Social play and grooming are typical affiliative interactions for many primate
      species, and are thought to have similar biological functions. However, grooming
      increases with age, whereas social play decreases. We proposed the hypothesis
      that both social grooming and social play in juveniles strengthen their social
      bonds in daily activities. We carried out field research on the social
      relationships among juvenile wild Japanese macaques in a troop in Kinkazan,
      Miyagi Prefecture, Japan, from fall 2007 to spring 2008 to investigate this
      hypothesis. We evaluated three relationships among juveniles, play indices (PI),
      grooming indices (GI), and 3-m-proximity indices (3mI) of each dyad (i.e.,
      interacting pair), and compared these social networks based on the matrices of
      the indices. The play and grooming networks were correlated with the association
      network throughout the two research periods. The multiple network level
      measurements of the play network, but not the grooming network, resembled those
      of the association network. Using a causal step approach, we showed that social
      play and grooming interactions in fall seem to predict associations in the
      following spring, controlling for the PI and GI matrix in spring, respectively.
      Social play and grooming for each juvenile were negatively correlated. The
      results partially support our predictions; therefore, the hypothesis that the
      biological function of social play among immature Japanese macaques is to
      strengthen their social bonds in the near future and develop their social life
      appears to be correct. For juvenile macaques, social play, rather than grooming,
      functions as an important social mechanism to strengthen affiliative
      relationships.

PMID- 29194705
TI  - Reply.

PMID- 29194706
TI  - Vectorial status of the Asian tiger mosquito Aedes albopictus of La Reunion
      Island for Zika virus.
AB  - La Reunion Island has been the scene of unusually large epidemics of dengue and
      chikungunya viruses with Aedes albopictus as the sole vector. After experimental
      oral infection, Ae. albopictus from La Reunion Island can disseminate both dengue
      and chikungunya viruses but not the Asian genotype of Zika virus, suggesting a
      strong midgut barrier to dissemination. Autochthonous transmission of the Asian
      genotype of Zika virus is improbable on La Reunion Island.

PMID- 29194707
TI  - Splanchnic vein thrombosis in patients with myeloproliferative neoplasms: The
      Mayo clinic experience with 84 consecutive cases.

PMID- 29194708
TI  - Metastatic serous carcinoma presenting as inflammatory carcinoma over the breast
      Report of two cases and literature review.
AB  - Non-mammary metastases involving breast are rare and most commonly involve the
      breast parenchyma. Infrequently, metastasis from an extramammary primary site
      presents as inflammatory carcinoma over the breast. Diagnosis of such lesions can
      be challenging, especially in patients with coexisting primary breast carcinoma.
      Few such cases have been described in literature; however, none of the previously
      reported cases had a prior history of primary breast carcinoma. We present 2
      patients with history of breast carcinoma and serous carcinoma of
      ovarian/peritoneal origin that presented with inflammatory carcinoma over the
      breast. Biopsies from breast tissue showed atypical cells in the dermis forming
      cords and papillary structures. Histopathologic differential diagnosis included
      infiltrating ductal carcinoma of breast origin and metastatic serous carcinoma.
      Immunohistochemical studies showed that the tumor cells were positive for markers
      of ovarian origin such as PAX-8 and CA-125 and negative for breast markers such
      as GATA-3, thus supporting the diagnosis. In summary, we describe the unusual
      presentation of metastatic serous carcinoma as inflammatory carcinoma over breast
      and discuss the diagnostic challenges in patients with coexisting primary breast
      and ovarian malignancies. We also review the morphologic features of tumors of
      breast and ovarian origin and the immunohistochemical stains to differentiate
      these 2 entities.

PMID- 29194709
TI  - Low-grade spindle cell proliferation in clear cell renal cell carcinoma is
      unlikely to be an initial step in sarcomatoid differentiation.
AB  - AIMS: Spindle cell proliferation within clear cell renal cell carcinoma (ccRCC)
      is usually considered as a sarcomatoid differentiation. Low-grade spindle cell
      proliferation (LG-SCP) in ccRCC was first described in 2001. This phenomenon is
      not common and can pose diagnostic challenges, particularly in core biopsies. The
      aim of this study was to describe morphological, immunohistochemical and
      molecular characteristics of ccRCCs with LG-SCP. METHODS AND RESULTS: Eleven
      cases of ccRCC with LG-SCP were retrieved from approximately 21 000 renal tumours
      in our registry. Ten cases of conventional ccRCC and 10 cases of typical
      sarcomatoid ccRCC were included as control groups. Morphological and
      immunohistochemical characteristics of epithelial-mesenchymal transition (EMT)
      were analysed. Von Hippel-Lindau syndrome gene abnormalities were also analysed
      using molecular genetics. Among ccRCC with LG-SCP cases, there were five males
      and five females (clinical information was not available in one case) with a
      median age of 67 years (mean: 68.5, range: 60-81 years). Average tumour size was
      7.1 cm (median:7.5, range:1.7-12 cm). Follow-up data were available in nine cases
      (mean: 44.78 months), with no aggressive behaviour seen. On average, LG-SCP areas
      constituted 5-80% of tumour volume (mean: 32.3%). Necrotic/regressed areas were
      seen in all cases ranging from 5% to 30%. LG-SCP was clearly epithelial, with no
      mitoses or any evidence of mesenchymal differentiation. Immunohistochemical
      profile of LG-SCP was consistent with 'conventional' ccRCC. Compared with
      sarcomatoid ccRCC, some EMT markers showed alteration in LG-SCP, including lower
      expression of N-cadherin and Zeb1 as well as higher expression of E-cadherin.
      However, there were no significant differences in EMT markers between LG-SCP and
      conventional ccRCC. Abnormalities in VHL (mutations, LOH3p) were found in six of
      11 cases. CONCLUSIONS: Our findings showed that LG-SCP in ccRCC have comparable
      immunohistochemical and molecular characteristics to those seen in 'conventional'
      ccRCC. Further, immunohistochemical analysis of EMT markers showed that LG-SCP
      did not differ from 'conventional' ccRCC. We believe that LG-SCP is a part of
      morphological heterogeneity in ccRCCs and that they may not represent an initial
      stage of sarcomatoid differentiation. This is supported further by the fact that
      ccRCC with LG-SCP did not display more aggressive behaviour than 'conventional'
      ccRCC.

PMID- 29194710
TI  - Links between the discovery of primates and anatomical comparisons with humans,
      the chain of being, our place in nature, and racism.
AB  - I focus on the crucial links between the discovery of nonhuman primates by
      Westerners, discussions on our place in nature, the chain of being, racism, and
      the history of primate comparative anatomy and of so-called "anatomical human
      racial studies." Strikingly, for more than a millennium humans knew more about
      the internal anatomy of a single monkey species than about that of their own
      bodies. This is because Galen used monkeys to infer human anatomy, in line with
      the human-animal continuity implied by the Greek notion of scala naturae. With
      the rise of Christianity, nonhuman primates were increasingly seen in a negative
      way. A more positive view emerged in the 14th century when nonhuman primates were
      directly studied/seen by Europeans, culminating in Tyson's 1699 work showing that
      chimps share more gross anatomical similarities with humans than with monkeys.
      However, the discomfort caused by this human-chimp similarity then led to a new
      idea of animal-human discontinuity, now related not to anatomy but to
      "civilization": between Europeans vs. non-Europeans + other primates. Moreover,
      Linnaeus' Systema Naturae and the emergence of "anatomical racial studies"
      influenced by Camper's craniology then led to even more extreme ideas, such as
      the notion that Europeans were both mentally and morphologically "ideal."
      Unfortunately the biased and often incorrect "results" of such studies, combined
      with ideas based on Darwin's "struggle for survival", became crucial in
      propaganda that lead to the rise of eugenics in the end of the 19th/first half of
      20th centuries and that culminated in Nazism. Since the 1950s there has been an
      emphasis on the continuity/unity between all human groups and other primates, in
      great part influenced by what happened during World War 2. Reviews such as this
      one are, therefore, particularly necessary to illuminate and guard against
      attitudes against "the Other" and racist ideologies that are re-emerging in
      modern political discourse across the globe.

PMID- 29194711
TI  - Institutional decision to adopt Y90 as primary treatment for hepatocellular
      carcinoma informed by a 1,000-patient 15-year experience.
AB  - : Yttrium-90 transarterial radioembolization (TARE) is a locoregional therapy
      (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall
      survival (OS) outcomes in a 1,000-patient cohort acquired over a 15-year period.
      Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated
      with TARE as part of a prospective cohort study. A comprehensive review of
      toxicity and survival outcomes was performed. Outcomes were stratified by
      baseline Child-Pugh (CP) class, United Network for Organ Sharing (UNOS), and
      Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin
      laboratory toxicities were compared to baseline. OS outcomes were reported using
      censoring and intention-to-treat methodologies. All treatments were outpatient,
      with a median one treatment per patient. Five hundred six (51%) were CP A, 450
      (45%) CP B, and 44 (4%) CP C. Two hundred sixty-three (26%) patients were BCLC A,
      152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty-eight (37%) were
      UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A
      patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5-80.3)
      months, BCLC B 25.0 (CI, 17.3-30.5) months, and BCLC C 15.0 (CI, 13.8-17.7)
      months. In CP B patients, censored OS for BCLC A was 27 (CI, 21-30.2) months,
      BCLC B 15.0 (CI, 12.3-19.0) months, and BCLC C 8.0 (CI, 6.8-9.5) months. Forty
      nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin
      toxicities, respectively. CONCLUSION: Based on our experience with 1,000 patients
      over 15 years, we have made a decision to adopt TARE as the first-line
      transarterial LRT for patients with HCC. Our decision was informed by prospective
      data and incrementally reported demonstrating outcomes stratified by BCLC,
      applied as either neoadjuvant or definitive treatment. (Hepatology 2017).

PMID- 29194712
TI  - Anthracycline-induced acute myocarditis and ventricular fibrillation arrest.

PMID- 29194713
TI  - Intraspecific variation in the domestic cat bony labyrinth revealed by different
      measurement techniques.
AB  - The knowledge of intraspecific variation is important to make assumptions on an
      interspecific level. To study intraspecific variation in the bony labyrinth
      morphology of the domestic cat, eleven specimens of Felis silvestris catus and
      two additional subspecies (F. s. lybica, F. s. ornata) were investigated. The
      sample comprises skulls of adult males and females, as well as juvenile cats.
      Each bony labyrinth endocast was virtually reconstructed based on uCT scans. To
      estimate the radius of curvature of each inner ear semicircular canal, three
      different approaches were tested. The comparison of the different methods
      resulted in different absolute values for the measured radii. The assumed best
      structure to precisely characterize the size of a semicircular canal is the inner
      perimeter. Within the tested sample, the anterior semicircular canal is always
      the largest, while the posterior semicircular canal is the second largest and the
      lateral semicircular canal the smallest in most cases. The coefficient of
      variation lies below 10% for all bony labyrinth measurements within the sample.
      The inner perimeter values of each semicircular canal are similar within all
      investigated specimens, even though the skull length of adult cats is twice as
      long as that of juvenile cats. Thus, inner ear biometry of the domestic cat seems
      stable throughout growth series and can therefore be used for systematic and
      ecological studies and the inclusion of juvenile individuals is reasonable. It is
      noteworthy that the inner perimeter values of the semicircular canals do not vary
      as much as the values of the angles spanned between the three canals within the
      sample. The inner ear within the cat skull is oriented about 25 degrees  to 31
      degrees  to the palate (angle between the plane anchored to the lateral
      semicircular canals (SC) and the plane anchored to the palate). The cochlea coils
      between 3.00 and 3.25 turns in the investigated sample.

PMID- 29194714
TI  - Survival following salvage therapy for primary refractory peripheral T-cell
      lymphomas (PTCL).
AB  - Optimal salvage therapy for primary refractory peripheral T-cell lymphomas (PTCL)
      and the role of hematopoietic stem cell transplant (SCT) remain poorly defined.
      We conducted a retrospective review of clinical outcomes and prognostic factors
      in a single-center cohort of 93 patients with primary refractory PTCL, defined as
      progression during first-line therapy or relapse within 6 months of its
      completion. Clinical outcomes were poor in this population, with median event
      free survival (EFS) of 3.5 months, median overall survival (OS) of 9.1 months,
      and 34% 3-year survival. Outcomes were comparable in patients who progressed
      through first-line therapy and patients who achieved CR/PR and subsequently
      relapsed within 6 months. A majority exhibited high-risk features and had
      intermediate to high risk IPI, which correlated with inferior outcomes. There was
      no difference in outcomes between patients who received single-agent salvage
      regimens and patients who underwent traditional, multi-agent salvage regimens.
      Thus, participation in well-designed clinical trials should be encouraged in this
      population. Additionally, there may be a trend toward improved EFS and OS in
      patients who underwent autologous or allogeneic SCT compared to patients who
      achieved CR or PR but were not transplanted.

PMID- 29194715
TI  - Estimating the DINA model parameters using the No-U-Turn Sampler.
AB  - The deterministic inputs, noisy, "and" gate (DINA) model is a popular cognitive
      diagnosis model (CDM) in psychology and psychometrics used to identify test
      takers' profiles with respect to a set of latent attributes or skills. In this
      work, we propose an estimation method for the DINA model with the No-U-Turn
      Sampler (NUTS) algorithm, an extension to Hamiltonian Monte Carlo (HMC) method.
      We conduct a simulation study in order to evaluate the parameter recovery and
      efficiency of this new Markov chain Monte Carlo method and to compare it with two
      other Bayesian methods, the Metropolis Hastings and Gibbs sampling algorithms,
      and with a frequentist method, using the Expectation-Maximization (EM) algorithm.
      The results indicated that NUTS algorithm employed in the DINA model properly
      recovers all parameters and is accurate for all simulated scenarios. We apply
      this methodology in the mental health area in order to develop a new method of
      classification for respondents to the Beck Depression Inventory. The
      implementation of this method for the DINA model applied to other psychological
      tests has the potential to improve the medical diagnostic process.

PMID- 29194716
TI  - Scratching the surface of cholestatic itch treatments.

PMID- 29194717
TI  - Validity of Ultrasound Lung Comets for Assessment of the Severity of Interstitial
      Pneumonia.
AB  - OBJECTIVES: Ultrasound (US) lung comets are often observed in patients with
      interstitial lung disease or congestive heart failure, but few studies have
      explored the clinical importance of US lung comets in patients with the former
      condition. We explored whether the US lung comet number could be used to assess
      the severity of interstitial pneumonia. METHODS: Forty stable patients with
      interstitial pneumonia were examined. Lung comets evident on transthoracic US
      imaging in 12 selected regions of the posterior chest wall were analyzed. We
      defined lung comets accompanied by thickened and irregular pleural lines as
      interstitial US lung comets; these predominated in patients with interstitial
      pneumonia. The total number of interstitial US lung comets was correlated with
      the data from chest high-resolution computed tomography, pulmonary function
      tests, serologic tests, and the 6-minute walk test. RESULTS: The 40 patients
      included 16 with idiopathic pulmonary fibrosis and 24 with nonspecific
      interstitial pneumonia. Thirty-four patients had interstitial US lung comets,
      which were more common in the lower than the upper lung area. Good correlations
      were evident between the lung comet number and the extent of the reticular
      pattern on chest high-resolution computed tomography (r = 0.710; P < .01),
      predicted forced vital capacity (r = -0.614; P < .01), and lung diffusion
      capacity for carbon monoxide (r = -0.577; P < .01). Notably, the lung comet
      number had a strong negative correlation with the percutaneous oxygen saturation
      level after the 6-minute walk test (r = -0.751; P < .01). CONCLUSIONS: The number
      of interstitial US lung comets evident on transthoracic US imaging may be a
      valuable marker of disease severity in patients with interstitial pneumonia.

PMID- 29194719
TI  - Combined loss of HLA I and HLA II expression is more common in the non-GCB type
      of diffuse large B cell lymphoma.

PMID- 29194720
TI  - A report on the oral health status of children with cerebral palsy in Dubai,
      United Arab Emirates.

PMID- 29194718
TI  - Prediction of olanzapine exposure in individual patients using physiologically
      based pharmacokinetic modelling and simulation.
AB  - AIM: The aim of the present study was to predict olanzapine (OLZ) exposure in
      individual patients using physiologically based pharmacokinetic modelling and
      simulation (PBPK M&S). METHODS: A 'bottom-up' PBPK model for OLZ was constructed
      in Simcyp(r) (V14.1) and validated against pharmacokinetic studies and data from
      therapeutic drug monitoring (TDM). The physiological, demographic and genetic
      attributes of the 'healthy volunteer population' file in Simcyp(r) were then
      individualized to create 'virtual twins' of 14 patients. The predicted systemic
      exposure of OLZ in virtual twins was compared with measured concentration in
      corresponding patients. Predicted exposures were used to calculate a hypothetical
      decrease in exposure variability after OLZ dose adjustment. RESULTS: The
      pharmacokinetic parameters of OLZ from single-dose studies were accurately
      predicted in healthy Caucasians [mean-fold errors (MFEs) ranged from 0.68 to
      1.14], healthy Chinese (MFEs 0.82 to 1.18) and geriatric Caucasians (MFEs 0.55 to
      1.30). Cumulative frequency plots of trough OLZ concentration were comparable
      between the virtual population and patients in a TDM database. After creating
      virtual twins in Simcyp(r), the R2 values for predicted vs. observed trough OLZ
      concentrations were 0.833 for the full cohort of 14 patients and 0.884 for the 7
      patients who had additional cytochrome P450 2C8 genotyping. The variability in
      OLZ exposure following hypothetical dose adjustment guided by PBPK M&S was
      twofold lower compared with a fixed-dose regimen - coefficient of variation
      values were 0.18 and 0.37, respectively. CONCLUSIONS: Olanzapine exposure in
      individual patients was predicted using PBPK M&S. Repurposing of available PBPK
      M&S platforms is an option for model-informed precision dosing and requires
      further study to examine clinical potential.

PMID- 29194721
TI  - Initial experiences with NAM-assisted primary repair of the BCLP deformity.
AB  - BACKGROUND: Primary surgical repair of the bilateral cleft lip and palate (BCLP)
      deformity is challenging. Infant Orthopedic (IO) procedures are often used to
      assist surgical reconstruction of normal anatomy. Nasoalveolar molding (NAM) is a
      presurgical infant orthopedic procedure that attempts to reduce the cleft nasal
      deformity, in addition to the lip and alveolus, leading to an esthetic primary
      surgical repair. OBJECTIVE: NAM provides the surgical team with a better
      foundation for an easier and more esthetic single stage repair at the level of
      nose in addition to the lip and alveolus. METHOD: Infant nasal cartilages are
      amenable to correction with NAM in the first few weeks of infancy when they
      retain their plasticity. NAM-assisted surgical repair of a complete BCLP infant
      is discussed. Postoperatively nasal stents were used to retain results and
      minimize relapse. RESULTS: NAM helped correct premaxillary deviation and
      protrusion, reduce alveolar cleft width and improve the nasal morphology prior to
      surgery in the BCLP infant. CONCLUSIONS: NAM helped reduce the severity of the
      cleft deformity in the BCLP infant and facilitated an easier and esthetic single
      stage primary surgical repair.

PMID- 29194722
TI  - The RNA genome of hepatitis E virus robustly triggers an antiviral interferon
      response.
AB  - : The outcomes of hepatitis E virus (HEV) infection are diverse, ranging from
      asymptomatic carrier, self-limiting acute infection, and fulminant hepatitis to
      persistent infection. This is closely associated with the immunological status of
      the host. This study aimed to understand the innate cellular immunity as the
      first-line defense mechanism in response to HEV infection. Phosphorylation of
      signal transducer and activator of transcription 1, a hallmark of the activation
      of antiviral interferon (IFN) response, was observed in the liver tissues of the
      majority of HEV-infected patients but not in the liver of uninfected individuals.
      In cultured cell lines and primary liver organoids, we found that HEV RNA genome
      potently induced IFN production and antiviral response. This mechanism is
      conserved among different HEV strains, including genotypes 1, 3, and 7 as tested.
      Interestingly, single-stranded HEV RNA is sufficient to trigger the antiviral
      response, without the requirement of viral RNA synthesis and the generation of an
      RNA replicative form or replicative intermediate. Surprisingly, the m7 G cap and
      poly A tail are not required, although both are key features of the HEV genome.
      Mechanistically, this antiviral response occurs in a retinoic acid-inducible gene
      I-independent, melanoma differentiation-associated protein 5-independent,
      mitochondrial antiviral signaling protein-independent, and beta-catenin
      independent but IRF3-dependent and IRF7-dependent manner. Furthermore, the
      integrity of the Janus kinase-signal transducer and activator of transcription
      pathway is essentially required. CONCLUSION: HEV infection elicits an active IFN
      related antiviral response in vitro and in patients, triggered by the viral RNA
      and mediated by IFN regulatory factors 3 and 7 and the Janus kinase-signal
      transducer and activator of transcription cascade; these findings have revealed
      new insights into HEV-host interactions and provided the basis for understanding
      the pathogenesis and outcome of HEV infection. (Hepatology 2018;67:2096-2112).

PMID- 29194723
TI  - Long-term clinical efficacy and safety of secukinumab for Japanese patients with
      psoriasis: A single-center experience.
AB  - Secukinumab is a fully human monoclonal antibody that can selectively neutralize
      interleukin-17A, and its excellent efficacy has been demonstrated in clinical
      trials for psoriasis. The aim of our study is to assess long-term efficacy and
      safety of secukinumab for 52 weeks in real-world clinical practise in our
      facility. A total of 83 patients (71 with psoriasis vulgaris and 12 with
      psoriatic arthritis) were included, and 49 of them were bio-switched patients.
      Psoriasis Area and Severity Index (PASI) 75 and PASI-90 responses were 80% and
      64% at week 12, 77% and 65% at week 24, and 76% and 58% at week 52, respectively.
      No significant differences were observed in efficacy between bio-naive and bio
      switched patients. Arthralgia showed improvement by week 12 in all patients with
      psoriatic arthritis with a reduction of serum C-reactive protein level. Treatment
      was discontinued in 22% (18/83), including eight patients with no improvement or
      exacerbation of cutaneous manifestations, one patient with new onset of arthritis
      and two patients with transient infection. Overall, secukinumab showed a
      sustained clinical response with an acceptable safety profile through week 52 in
      Japanese psoriatic patients.

PMID- 29194724
TI  - Reply.

PMID- 29194725
TI  - Levels of serum sclerostin, metabolic parameters, and periodontitis in 
      postmenopausal women with diabetes.
AB  - Diabetes mellitus (DM) is a metabolic disease defined by hyperglycemia, which is
      associated with periodontal disease and exerts an effect on bone metabolism. The
      aim of this study was to determine serum levels of sclerostin in postmenopausal
      women with diabetes and determine a possible association with periodontal
      disease. Sixty-one postmenopausal women (32 with diabetes and 29 without
      diabetes) were evaluated. Blood was collected for biochemical analysis and the
      determination of serum sclerostin. The participants were also submitted to a
      clinical examination for the evaluation of periodontal status. A total of 75.4%
      of the volunteers had periodontal disease and levels serum sclerostin were
      altered in 48.7% of the patients with diabetes. In the diabetic population, mean
      levels of LDL (p = 0.035) and urea (p = 0.032) were higher in the patients
      without periodontal disease and the plaque index was higher in those with
      periodontal disease (p = 0.039). The prevalence of periodontal disease and the
      levels serum sclerostin were high in the postmenopausal women analyzed, but the
      data do not allow the determination of whether periodontal disease is related to
      high levels of this peptide.

PMID- 29194726
TI  - The effects of acaricide treatment of sheep on red grouse Lagopus lagopus scotica
      tick burdens and productivity in a multi-host system.
AB  - Ixodes ricinus (Ixodida: Ixodidae) ticks are of economic and pathogenic
      importance across Europe. Within the uplands of the U.K., management to reduce
      ticks is undertaken to benefit red grouse Lagopus lagopus scotica (Galliformes:
      Phasianidae). Management strategies focus on the acaricide treatment of domestic
      sheep Ovis aries (Artiodactyla: Bovidae), but the effectiveness of this is less
      certain in the presence of wild hosts, particularly red deer Cervus elaphus
      (Artiodactyla: Cervidae) and mountain hare Lepus timidus (Lagomorpha: Leporidae).
      This study examines the effects of sheep management on grouse tick burdens and
      productivity using sites with a range of wild host densities. Sites at which
      applications of acaricide were more frequent had lower tick burdens; this
      relationship was similar on sites with a range of deer densities. However, no
      direct link was detected between acaricide treatment interval and grouse
      productivity. Sites with higher deer densities had higher grouse tick burdens and
      lower productivity [mean +/- standard error (SE) young : adult ratio: 1.2 +/-
      0.2] compared with sites with lower deer densities (mean +/- SE young : adult
      ratio: 1.8 +/- 0.1). Sites with higher grouse brood sizes and higher proportions
      of hens with broods were also those with higher mountain hare abundance indices.
      This study highlights the importance of the frequent treatment of sheep with
      acaricide to reduce tick burdens on grouse, even in the presence of wild hosts.

PMID- 29194727
TI  - Diminished cerebral oxygen extraction and metabolic rate in sickle cell disease
      using T2 relaxation under spin tagging MRI.
AB  - PURPOSE: T2 MRI oximetry can noninvasively determine oxygen saturation (Y) but
      requires empirical MR calibration models to convert the measured blood transverse
      relaxation (T2b ) into Y. The accuracy of existing T2b models in the presence of
      blood disorders such as sickle cell disease (SCD) remains unknown. METHODS: A
      Carr Purcell Meiboom Gill T2 preparation sequence was used to make 83 whole blood
      measurements from 11 subjects with SCD to derive an ex vivo sickle hemoglobin
      (HbS) T2b model. Forearm venous blood gas, sagittal sinus T2 (T2 Relaxation Under
      Spin Tagging) and total brain blood flow (phase contrast MRI) were measured in 37
      healthy controls and 33 SCD subjects (age 24.6 +/- 10.2 years). Cerebral oxygen
      saturation, extraction fraction, and metabolic rate estimates were calculated
      using three separate T2b models. Cerebral and forearm oxygen extraction fraction
      were compared. RESULTS: Ex vivo, SCD blood had greater saturation dependent
      relaxivity than control blood, with a weak dependence on HbS and no dependence on
      hematocrit. In vivo, the HbS T2b model predicted Yv values with lowest
      coefficient of variation (compared with existing T2b models) and the strongest
      correlation with peripheral venous oximetry (r2  = .29). The HbS T2b model
      predicted systematically higher Yv measurements in SCD patients (73 +/- 5 and 61
      +/- 6; P < 0.0001) which was mirrored by peripheral venous measurements (75 +/-
      20 and 45 +/- 20; P < 0.0001). CONCLUSION: Cerebral and peripheral oxygen
      extraction are decreased in SCD patients, suggesting either blood flow is
      increased beyond metabolic demands or the presence of physiological arterial
      venous shunting. Magn Reson Med 80:294-303, 2018. (c) 2017 International Society
      for Magnetic Resonance in Medicine.

PMID- 29194728
TI  - CDK4 expression in chordoma: A potential therapeutic target.
AB  - Chordomas are rare bone tumors and treatment is commonly based on a combination
      of surgery and radiotherapy. There is no standard chemotherapy treatment for
      chordoma. The aim of this study was to determine the expression of cyclin
      dependent kinase 4 (CDK4) in chordoma and its therapeutic implications. We
      evaluated CDK4 expression both in chordoma cell lines and in chordoma tissues.
      Also, we investigated the functional roles of CDK4 in chordoma cell growth and
      proliferation. Furthermore, the therapeutic implications of targeting CDK4 in
      chordoma were evaluated. We found CDK4 highly expressed in chordoma cell lines
      and in a majority (97.7%) of chordoma tissues. Higher CDK4 expression correlated
      with metastasis and recurrence of chordoma. Treatment of chordoma cells using
      CDK4 inhibitor palbociclib could efficiently inhibit chordoma cells growth and
      proliferation. These data demonstrate that targeting CDK4 may be useful as a
      novel strategy in the treatment of chordoma. (c) 2017 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1581-1589, 2018.

PMID- 29194729
TI  - How to Improve Information on Medication Exposure during Pregnancy.

PMID- 29194730
TI  - Novel pyridine-2,4,6-tricarbohydrazide thiourea compounds as small key organic
      molecules for the potential treatment of type-2 diabetes mellitus: In vitro
      studies against yeast alpha- and beta-glucosidase and in silico molecular
      modeling.
AB  - A range of novel pyridine-2,4,6-tricarbohydrazide thiourea compounds (4a-i) were
      synthesized in good to excellent yields (63-92%). The enzyme inhibitory
      potentials of these compounds were investigated against alpha- and beta
      glucosidases because these enzymes play a crucial role in treating type-2
      diabetes mellitus (T2DM). As compared to the reference compound acarbose (IC50
      38.22 +/- 0.12 MUM), compounds 4i (IC50 25.49 +/- 0.67 MUM), 4f (IC50 28.91 +/-
      0.43 MUM), 4h (IC50 30.66 +/- 0.52 MUM), and 4e (IC50 35.01 +/- 0.45 MUM)
      delivered better inhibition against alpha-glucosidase and were quite
      inactive/completely inactive against beta-glucosidase. The structure-activity
      relationship of these compounds was developed and elaborated with the help of
      molecular docking studies.

PMID- 29194731
TI  - Human mesenchymal stem cells induced to differentiate as chondrocytes follow a
      biphasic pattern of extracellular matrix production.
AB  - Regenerative medicine and tissue engineering studies are actively developing
      novel means to repair adult articular cartilage defects using biological
      approaches. One such approach is the harnessing of adult human therapeutic cells
      such as those referred to as mesenchymal stem cells. Upon exposure to
      chondrogenic signals, these cells differentiate and initiate the production of a
      complex and voluminous cartilaginous matrix that is crucial to both the structure
      and function of cartilage. Furthermore, this complexity requires the time
      sensitive activation of a large number of genes to produce the components of this
      matrix. The current study analyzed the kinetics of matrix production in an
      aggregate culture model where adult human mesenchymal stem cells were induced to
      differentiate as chondrocytes. The results indicate the existence of a biphasic
      mode of differentiation and maturation during which matrix genes and molecules
      are differentially activated and secreted. These results have important
      implications for developing novel approaches for the creation of tissue
      engineered articular cartilage. (c) 2017 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 36:1757-1766, 2018.

PMID- 29194732
TI  - Doppler ultrasound triggering for cardiac MRI at 7T.
AB  - PURPOSE: A prerequisite for cardiac MR (CMR) imaging is adequate synchronization
      of image acquisition with the cardiac cycle. Electrocardiogram triggering may be
      hampered by electromagnetic interferences at high field strength. The purpose of
      this work is to evaluate the feasibility of Doppler ultrasound triggering for CMR
      image synchronization at 7T ultra-high-field MRI. METHODS: A custom-built Doppler
      ultrasound (DUS) trigger device was developed. Magnetic resonance compatibility
      was evaluated using E- and H-field probes and flip angle maps prior to the study.
      Cardiac MR was performed at 7T in 13 healthy subjects using DUS and pulse
      oximetry for triggering. For validation of the trigger signal, the
      electrocardiogram, pulse, and DUS signals were compared outside of the MR room.
      Breath-hold cine fast low-angle-shot sequences were acquired in short-axis and
      four-chamber view. Image quality was assessed by two senior radiologists and by
      measurement of endocardial blurring. RESULTS: The maximal change in E- and H
      field distributions with and without transducer was 5%. No interferences were
      observed between DUS and MRI in the B1 maps and during CMR imaging. Validation of
      the DUS trigger signal resulted in a high correlation to the electrocardiographic
      signal of r = 0.99. Analysis of image and trigger quality revealed no significant
      differences. CONCLUSION: Doppler ultrasound was applied as a new trigger method
      in CMR at 7T. The transmission line and transducer were locally approved as 7T MR
      conditional, and were successfully tested for image synchronization at 7T. In the
      future, this method needs to be evaluated in a larger patient population. Magn
      Reson Med 80:239-247, 2018. (c) 2017 International Society for Magnetic Resonance
      in Medicine.

PMID- 29194733
TI  - Activity of Group 2 Innate Lymphoid Cells is Associated with Chronic Inflammation
      and Dysregulated Metabolic Homoeostasis in Type 2 Diabetic Nephropathy.
AB  - The metabolic syndrome (MS) is an independent risk factor for type 2 diabetic
      nephropathy and accompanied by subclinical inflammation which involves immune
      deriving factors. Emerging studies indicate that group 2 innate lymphoid cells
      (ILC2s) can regulate adipose metabolism, but much less is known about the
      activity of ILC2s in metabolic imbalance in obesity and diabetes. This study
      explored the effect of ILC2s-related molecules on the occurrence of MS in type 2
      diabetic nephropathy. Thirty patients with type 2 diabetic nephropathy were
      included in the study; the mRNA expression of ILC2s-associated molecules from
      peripheral blood mononuclear cell and the correlation of the ILC2s activity and
      the MS-related indicators were analysed. The results indicated that the waist
      circumference, fasting blood glucose, systolic blood pressure, diastolic blood
      pressure and triglyceride in patients with simple diabetes and diabetic
      nephropathy were increased, and the incidence of MS was 46.67% and 86.67%,
      respectively. The ILC2s-associated factors RORalpha, T1/ST2 and IL-5/IL-13 mRNA
      were increased in diabetic nephropathy. There was a positive correlation between
      the expression level of IL-13 or T1/ST2 mRNA and some MS indexes. In addition,
      the levels of plasma sTNFR, eotaxin-2 and I-309 were also increased in patients
      with type 2 diabetic nephropathy. It suggested that the patients with type 2
      diabetic nephropathy were more likely to have multiple components of MS than
      those with simple type 2 diabetes mellitus, and enhanced ILC2s activity might be
      involved in the formation of MS in diabetic nephropathy via influencing blood
      pressure and lipid metabolism.

PMID- 29194734
TI  - In vivo characterization of brain ultrashort-T2 components.
AB  - PURPOSE: Recent nuclear magnetic resonance and MRI studies have measured a fast
      relaxing signal component with T2*<1 ms in white matter and myelin extracts. In
      ex vivo studies, evidence suggests that a large fraction of this component
      directly arises from bound protons in the myelin phospholipid membranes. Based on
      these results, this ultrashort-T2 component in nervous tissue is a new potential
      imaging biomarker of myelination, which plays a critical role in neuronal signal
      conduction across the brain and loss or degradation of myelin is a key feature of
      many neurological disorders. The goal of this work was to characterize the
      relaxation times and frequency shifts of ultrashort-T2 components in the human
      brain. METHODS: This required development of an ultrashort echo time relaxometry
      acquisition strategy and fitting procedure for robust measurements in the
      presence of ultrashort T2* relaxation times and large frequency shifts. RESULTS:
      We measured an ultrashort-T2 component in healthy volunteers with a median T2*
      between 0.5-0.7 ms at 3T and 0.2-0.3 ms at 7T as well as an approximately -3 ppm
      frequency shift from water. CONCLUSION: To our knowledge, this is the first time
      a chemical shift of the ultrashort-T2 brain component has been measured in vivo.
      This chemical shift, at around 1.7 ppm, is similar to the primary resonance of
      most lipids, indicating that much of the ultrashort-T2 component observed in vivo
      arises from bound protons in the myelin phospholipid membranes. Magn Reson Med
      80:726-735, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 29194735
TI  - Paradoxic eczema in infants after heart transplantation.
AB  - New-onset psoriasis in patients receiving tumor necrosis factor inhibitors is
      well recognized in children and adults. We describe three children who underwent
      cardiac transplantation and developed an analogous form of paradoxic eczema
      occurring 2-48 months after starting systemic tacrolimus, a drug widely used
      topically to treat eczema. Anecdotal reports and our experience suggest that
      tacrolimus taper with alternative systemic antirejection immunosuppressant may
      lead to skin clearance. Pending additional insight, treatment should include
      optimizing skin barrier function, minimizing microbial and allergic triggers, and
      coordinating care to choose the best-tolerated systemic immunosuppressant regimen
      at the lowest effective dose.

PMID- 29194737
TI  - Differential expression of a fructose receptor gene in honey bee workers
      according to age and behavioral role.
AB  - Honey bee (Apis mellifera) workers contribute to the maintenance of colonies in
      various ways. The primary functions of workers are divided into two types
      depending on age: young workers (nurses) primarily engage in such behaviors as
      cleaning and food handling within the hive, whereas older workers (foragers)
      acquire floral nutrients beyond the colony. Concomitant with this age-dependent
      change in activity, physiological changes occur in the tissues and organs of
      workers. Nurses supply younger larvae with honey containing high levels of
      glucose and supply older larvae with honey containing high levels of fructose.
      Given that nurses must determine both the concentration and type of sugar used in
      honey, gustatory receptors (Gr) expressed in the chemosensory organs likely play
      a role in distinguishing between sugars. Glucose is recognized by Gr1 in honey
      bees (AmGr1); however, it remains unclear which Gr are responsible for fructose
      recognition. This study aimed to identify fructose receptors in honey bees and
      reported that AmGr3, when transiently expressed in Xenopus oocytes, responded
      only to fructose, and to no other sugars. We analyzed expression levels of AmGr3
      to identify which tissues and organs of workers are involved in fructose
      recognition and determined that expression of AmGr3 was particularly high in the
      antennae and legs of nurses. Our results suggest that nurses use their antennae
      and legs to recognize fructose, and that AmGr3 functions as an accurate nutrient
      sensor used to maintain food quality in honey bee hives.

PMID- 29194739
TI  - Transverse signal decay under the weak field approximation: Theory and
      validation.
AB  - PURPOSE: To derive an expression for the transverse signal time course from
      systems in the motional narrowing regime, such as water diffusing in blood. This
      was validated in silico and experimentally with ex vivo blood samples. METHODS: A
      closed-form solution (CFS) for transverse signal decay under any train of
      refocusing pulses was derived using the weak field approximation. The CFS was
      validated via simulations of water molecules diffusing in the presence of
      spherical perturbers, with a range of sizes and under various pulse sequences.
      The CFS was compared with more conventional fits assuming monoexponential decay,
      including chemical exchange, using ex vivo blood Carr-Purcell-Meiboom-Gill data.
      RESULTS: From simulations, the CFS was shown to be valid in the motional
      narrowing regime and partially into the intermediate dephasing regime, with
      increased accuracy with increasing Carr-Purcell-Meiboom-Gill refocusing rate. In
      theoretical calculations of the CFS, fitting for the transverse relaxation rate
      (R2 ) gave excellent agreement with the weak field approximation expression for
      R2 for Carr-Purcell-Meiboom-Gill sequences, but diverged for free induction
      decay. These same results were confirmed in the ex vivo analysis. CONCLUSION:
      Transverse signal decay in the motional narrowing regime can be accurately
      described analytically. This theory has applications in areas such as tissue iron
      imaging, relaxometry of blood, and contrast agent imaging. Magn Reson Med 80:341
      350, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 29194738
TI  - Cardiac MR elastography using reduced-FOV, single-shot, spin-echo EPI.
AB  - PURPOSE: To implement a reduced field of view (rFOV) technique for cardiac MR
      elastography (MRE) and to demonstrate the improvement in image quality of both
      magnitude images and post-processed MRE stiffness maps compared to the
      conventional full field of view (full-FOV) acquisition. METHODS: With
      Institutional Review Board approval, 17 healthy volunteers underwent both full
      FOV and rFOV cardiac MRE scans using 140-Hz vibrations. Two cardiac radiologists
      blindly compared the magnitude images and stiffness maps and graded the images
      based on several image quality attributes using a 5-point ordinal scale. Fisher's
      combined probability test was performed to assess the overall evaluation. The
      octahedral shear strain-based signal-to-noise ratio (OSS-SNR) and median
      stiffness over the left ventricular myocardium were also compared. RESULTS: One
      volunteer was excluded because of an inconsistent imaging resolution during the
      exam. In the remaining 16 volunteers (9 males, 7 females), the rFOV scans
      outperformed the full-FOV scans in terms of subjective image quality and ghosting
      artifacts in the magnitude images and stiffness maps, as well as the overall
      preference. The quantitative measurements showed that rFOV had significantly
      higher OSS-SNR (median: 1.4 [95% confidence interval (CI): 1.2-1.5] vs. 2.1 [95%
      CI: 1.8-2.4]), P < 0.05) compared to full-FOV. Although no significant change was
      found in the median myocardial stiffness between the 2 scans, we observed a
      decrease in the stiffness variation within the myocardium from 2.1 kPa (95% CI:
      [1.9, 2.3]) to 1.9 kPa (95% CI: [1.7, 2.0]) for full-FOV and rFOV, respectively
      (P < 0.05) in a subgroup of 7 subjects with ghosting present in the myocardium.
      CONCLUSION: This pilot volunteer study demonstrated that rFOV cardiac MRE has the
      capability to reduce ghosting and to improve image quality in both MRE magnitude
      images and stiffness maps. Magn Reson Med 80:231-238, 2018. (c) 2017 The Authors
      Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of
      International Society for Magnetic Resonance in Medicine. 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- 29194736
TI  - MicroRNAs in orthopaedic research: Disease associations, potential therapeutic
      applications, and perspectives.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that function to control many
      cellular processes by their ability to suppress expression of specific target
      genes. Tens to hundreds of target genes may be affected by one miRNA, thereby
      resulting in modulation of multiple pathways in any given cell type. Therefore,
      altered expression of miRNAs (i.e., during tissue development or in scenarios of
      disease or cellular stress) can have a profound impact on processes regulating
      cell differentiation, metabolism, proliferation, or apoptosis, for example. Over
      the past 5-10 years, thousands of reports have been published on miRNAs in
      cartilage and bone biology or disease, thus highlighting the significance of
      these non-coding RNAs in regulating skeletal development and homeostasis. For the
      purpose of this review, we will focus on miRNAs or miRNA families that have
      demonstrated function in vivo within the context of cartilage, bone or other
      orthopaedic-related tissues (excluding muscle). Specifically, we will discuss
      studies that have utilized miRNA transgenic mouse models or in vivo approaches to
      target a miRNA with the aim of altering conditions such as osteoarthritis,
      osteoporosis and bone fractures in rodents. We will not discuss miRNAs in the
      context skeletal cancers since this topic is worthy of a review of its own.
      Overall, we aim to provide a comprehensive description of where the field
      currently stands with respect to the therapeutic potential of specific miRNAs to
      treat orthopaedic conditions and current technologies to target and modify miRNA
      function in vivo. (c) 2017 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 36:33-51, 2018.

PMID- 29194740
TI  - Stereotype Threat Effects on Learning From a Cognitively Demanding Mathematics
      Lesson.
AB  - Stereotype threat-a situational context in which individuals are concerned about
      confirming a negative stereotype-is often shown to impact test performance, with
      one hypothesized mechanism being that cognitive resources are temporarily co
      opted by intrusive thoughts and worries, leading individuals to underperform
      despite high content knowledge and ability (see Schmader & Beilock, ). We test
      here whether stereotype threat may also impact initial student learning and
      knowledge formation when experienced prior to instruction. Predominantly African
      American fifth-grade students provided either their race or the date before a
      videotaped, conceptually demanding mathematics lesson. Students who gave their
      race retained less learning over time, enjoyed the lesson less, reported a
      diminished desire to learn more, and were less likely to choose to engage in an
      optional math activity. The detrimental impact was greatest among students with
      high baseline cognitive resources. While stereotype threat has been well
      documented to harm test performance, the finding that effects extend to initial
      learning suggests that stereotype threat's contribution to achievement gaps may
      be greatly underestimated.

PMID- 29194741
TI  - "Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p
      deletion and 8q24 gain.
AB  - Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a
      lack of response to standard treatment and thus the worst possible clinical
      outcome. Various chromosomal abnormalities (including unbalanced translocations,
      deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one
      copy of the TP53 gene. The objective of the present study was to determine
      whether the type of chromosomal abnormality leading to 17p- and the additional
      aberrations influenced the prognosis in a series of 195 patients with 17p-CLL.
      Loss of 17p resulted primarily from an unbalanced translocation (70%) with
      several chromosome partners (the most frequent being chromosome 18q), followed by
      deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring
      chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex
      karyotype (>=5 abnormalities), and 8q24 gain were associated with poor treatment
      free survival, and i(17q) (P = .04), unbalanced translocations (P = .03) and 8q24
      gain (P = .001) were significantly associated with poor overall survival. In a
      multivariate analysis, 8q24 gain remained a significant predictor of poor overall
      survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact
      on outcome, and so patients with this "double-hit" CLL have a particularly poor
      prognosis. Systematic, targeting screening for 8q24 gain should therefore be
      considered in cases of 17p- CLL.

PMID- 29194742
TI  - Highly variable clinical feature and course of aggressive digital papillary
      adenocarcinoma.
AB  - Aggressive digital papillary adenocarcinoma (ADPA) is a rare cutaneous tumor with
      sweat gland differentiation. Due to the high risk of local recurrence and delayed
      metastasis, the wide local resection of the primary lesion and long-term follow
      up are recommended for ADPA. Here, we report two cases of ADPA. Case 1 had a blue
      gray nodule on the tip of the right middle finger. Case 2 had had a papule on the
      dorsal side of the left ring finger for 13 years. In both cases, papillary
      proliferations of the tumor cells showed multilobular adenomatous structures with
      back-to-back patterns characteristic of ADPA. We amputated the finger at the
      proximal interphalangeal joint and performed a wide resection of the primary
      tumor in Case 1 and 2, respectively. Sentinel lymph node biopsy in the axilla was
      performed, and no sentinel lymph node metastasis was found in either case. Among
      the previously reported ADPA cases, clinically, most lesions were skin-colored or
      tan-brown to gray. The blue-gray color in Case 1 is thought to be extraordinary
      for ADPA. In Case 2, the patient had had the small lesion for more than 13 years
      and the tumor size had been stable during that long period. The present two cases
      suggest that ADPA shows a prominent variety of both clinical features and disease
      courses, and that we cannot exclude the possibility of ADPA even in cases of blue
      gray nodules or small, stable, non-progressive papules.

PMID- 29194743
TI  - Optimizing venous outflow in reconstruction of Gustilo IIIB lower extremity
      traumas with soft tissue free flap coverage: Are two veins better than one?
AB  - PURPOSE: The dependent nature of the lower extremity predisposes to venous
      congestion, especially following significant trauma. The benefit of a second
      venous anastomosis, however, remains unclear in lower extremity trauma free flap
      reconstruction. This study investigated the effect of an additional venous
      anastomosis on flap outcomes in lower extremity trauma reconstruction. METHODS:
      Retrospective review between 1979 and 2016 identified 361 soft tissue flaps
      performed for Gustilo IIIB/C coverage meeting inclusion criteria. Muscle flaps
      were performed in 287 cases (79.9%) and fasciocutaneous flaps in 72 cases
      (20.1%). Single-vein anastomosis was performed in 76% of cases and dual-vein
      anastmoses in 24% of cases. Patient demographics, flap characteristics, and
      outcomes were examined. RESULTS: Fasciocutaneous flaps were more likely to have
      two veins performed (P < .001). Complications occurred in 143 flaps (39.8%): 45
      take-backs (12.4%), 37 partial losses (10.3%), 31 complete losses (8.6%).
      Compared to single-vein flaps, two veins reduced major complications (P = .005),
      partial flap failures (P = .008), and any flap failure (P = .018). Multivariable
      regression analysis demonstrated two veins to be protective against complications
      (RR = 2.58, P = .009). Subset regression analysis by flap type demonstrated an
      even more significant reduction in complications among muscle flaps (RR = 3.92, P
      = .005). Additionally, a >1 mm vein size mismatch was predictive of total flap
      failure (RR = 3.02, P = .038). CONCLUSION: Lower extremity trauma free flaps with
      two venous anastomoses demonstrated a fourfold reduction in complication rates
      compared to single-vein flaps. Additionally, venous size mismatch >1 mm was an
      independent predictor of total flap failure, suggesting beneficial effects of
      both two-vein outflow and matched vessel diameter.

PMID- 29194744
TI  - Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals.
AB  - BACKGROUND: Seizures are a common manifestation of neurological disease in the
      neonatal foal and are an important cause of morbidity and mortality in this
      population. Current antiepileptic options are effective, but often have
      undesirable adverse effects, short duration of action and high cost.
      Levetiracetam has an ideal safety and pharmacokinetic profile in multiple
      species, including the adult horse, and may be a safe and cost-effective
      alternative anticonvulsant in neonatal foals. Due to differences in drug
      disposition and clearance dosages in neonates, dosing recommendations in other
      species or adult horses cannot be extrapolated to foals. OBJECTIVE: To establish
      the pharmacokinetic profile of single-dose i.v. and intragastric administration
      of levetiracetam in healthy neonatal foals. STUDY DESIGN: Randomised crossover
      experimental study. METHODS: Levetiracetam was administered as a single dose to
      six healthy foals (ages 1-10 days) at a dose of 32 mg/kg bwt i.v. or
      intragastrically. Plasma levetiracetam concentrations were measured using a
      validated HPLC protocol. RESULTS: After i.v. administration to healthy foals,
      levetiracetam had a mean (+/-s.d.) elimination half-life of 7.76 +/- 0.51 h, a
      mean systemic clearance of 61.67 +/- 10.96 (mL/h/kg) and a mean apparent volume
      of distribution at steady state of 0.670 +/- 0.124 (L/kg). Following intragastric
      administration, levetiracetam had a peak concentration of 38.34 +/- 7.42 mg/L and
      time to achieve peak concentration was 0.875 (0.5-1.5) h. Mean bioavailability
      for IG administration was excellent (103.04 +/- 14.51%). No significant
      differences in pharmacokinetic variables between routes and order of
      administration were observed. MAIN LIMITATIONS: Small sample size and single-dose
      administration. CONCLUSIONS: Levetiracetam has excellent intragastric
      bioavailability in foals and is predicted to maintain plasma concentrations at or
      above the proposed target concentration with twice daily i.v. or oral
      administration. Once-daily administration may be possible in some foals based on
      the therapeutic range recommended in other species.

PMID- 29194745
TI  - Biomechanical tolerance of whole lumbar spines in straightened posture subjected
      to axial acceleration.
AB  - Quantification of biomechanical tolerance is necessary for injury prediction and
      protection of vehicular occupants. This study experimentally quantified lumbar
      spine axial tolerance during accelerative environments simulating a variety of
      military and civilian scenarios. Intact human lumbar spines (T12-L5) were
      dynamically loaded using a custom-built drop tower. Twenty-three specimens were
      tested at sub-failure and failure levels consisting of peak axial forces between
      2.6 and 7.9 kN and corresponding peak accelerations between 7 and 57 g. Military
      aircraft ejection and helicopter crashes fall within these high axial
      acceleration ranges. Testing was stopped following injury detection. Both peak
      force and acceleration were significant (p < 0.0001) injury predictors. Injury
      probability curves using parametric survival analysis were created for peak
      acceleration and peak force. Fifty-percent probability of injury (95%CI) for
      force and acceleration were 4.5 (3.9-5.2 kN), and 16 (13-19 g). A majority of
      injuries affected the L1 spinal level. Peak axial forces and accelerations were
      greater for specimens that sustained multiple injuries or injuries at L2-L5
      spinal levels. In general, force-based tolerance was consistent with previous
      shorter-segment lumbar spine testing (3-5 vertebrae), although studies
      incorporating isolated vertebral bodies reported higher tolerance attributable to
      a different injury mechanism involving structural failure of the cortical shell.
      This study identified novel outcomes with regard to injury patterns, wherein more
      violent exposures produced more injuries in the caudal lumbar spine. This caudal
      migration was likely attributable to increased injury tolerance at lower lumbar
      spinal levels and a faster inertial mass recruitment process for high rate load
      application. Published 2017. This article is a U.S. Government work and is in the
      public domain in the USA. J Orthop Res 36:1747-1756, 2018.

PMID- 29194746
TI  - Pharmacokinetics of tiludronate in horses: A field population study.
AB  - BACKGROUND: Tiludronate is a bisphosphonate drug marketed to treat different bone
      conditions in horses. OBJECTIVES: The goal of this study was to measure the
      plasma concentrations of tiludronate in a population of race and sport horses
      under field conditions, and using pharmacokinetic population modelling, to
      estimate detection times for doping control. STUDY DESIGN: Prospective cohort.
      METHODS: This study was conducted under field conditions on 39 race or sport
      horses diagnosed with bone conditions based on a lameness examination and treated
      with tiludronate. Each horse received 1 mg/kg of tiludronate (Tildren(r) )
      intravenously (i.v.). Blood samples (from 1 to 4 per horse with a total of 93
      samples) were collected around 10, 20, 30, 40 and 50 days after tiludronate
      administration. Tiludronate was quantified by HPLC/ESI-MSn . Tiludronate
      concentrations were analysed using nonlinear mixed-effects modelling (population
      approach). Monte Carlo simulations were then used to compute a prediction
      interval to estimate the corresponding quantile of horses predicted to have
      concentrations below some potential screening limits. RESULTS: This study
      highlighted pharmacokinetic differences between healthy experimental horses and
      the population of horses being treated in the field as well as the effect of
      level of training on plasma tiludronate. Different detection times were computed
      corresponding to different possible screening limits. MAIN LIMITATIONS: The
      number of horses in each group was limited, and the specific disease being
      treated with tiludronate is unknown. CONCLUSIONS: This population pharmacokinetic
      study on tiludronate will enable racing and other sports authorities to provide a
      detection time reflecting field conditions for the medication control of
      tiludronate. More generally, our study design and the data modelling serve as an
      example of how to generate detection times directly from the target horse
      population rather than from experimental horses.

PMID- 29194747
TI  - Standardization of hemipelvis alignment for in vitro biomechanical testing.
AB  - Although in vitro biomechanical tests are regularly performed, the definition of
      a suitable reference frame for hemipelvic specimens is still a challenge. The
      aims of the present study were to: (i) define a reference frame for the human
      hemipelvis suitable for in vitro applications, based on robust anatomical
      landmarks; (ii) identify the alignment of a hemipelvis based on the alignment of
      a whole pelvis (including right/left and male/female differences); (iii) identify
      the relative alignment of the proposed in vitro reference frame with respect to a
      reference frame commonly used in gait analysis; (iv) create an in vitro alignment
      procedure easy, robust and inexpensive; (v) quantify the intra-operator
      repeatability and inter-operator reproducibility of the procedure. A procedure to
      univocally identify the anatomical landmarks was created, exploiting the in vitro
      accessibility of the specimen's surface. Through the analysis on 53 CT scans (106
      hemipelvises), the alignment of the hemipelvis based on the alignment of a whole
      pelvis was analyzed: differences between male/female and right/left hemipelvises
      were not statistically significant To overcome the uncertainty in the
      identification of the acetabular rim, a standard acetabular plane was defined. An
      alignment procedure was developed to implement such anatomical reference frame.
      The intra-operator repeatability and the inter-operator reproducibility were
      quantified with four operators, on male and female hemipelvises. The intra
      operator repeatability was better than 1.5 degrees . The inter-operator
      reproducibility was better than 2.0 degrees . Alignment in the transverse plane
      was the most repeatable. The presented procedure to align hemipelvic specimens is
      sufficiently robust, standardized, and accessible. (c) 2017 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1645-1652, 2018.

PMID- 29194748
TI  - Interleukin-17 and Toll-like Receptor 10 genetic polymorphisms and susceptibility
      to large joint osteoarthritis.
AB  - Primary osteoarthritis (OA) is the most common type of a joint disease. It has a
      polygenic risk inheritance pattern and affects older people. The etiology of this
      disease is not fully understood. The aim of this study was to investigate the
      associations between polymorphisms in pro-inflammatory interleukin-17 (IL17A and
      IL17F) and anti-inflammatory Toll-like Receptor 10 (TLR10) genes with the risk
      for development of advanced stage hip and knee primary OA in the Croatian
      population. A total of 500 OA patients and 597 controls were genotyped for IL17A
      SNP (rs2275913), IL17F SNPs (rs763780 and rs1889570), and TLR10 (rs11096957)
      genes. The allelic and genotypic frequencies of IL17F SNP (rs763780) showed
      statistically significant differences in comparisons of controls with hip-but not
      knee-OA patients. The major allele (T) of rs763780 was associated with the lower
      risk for developing hip OA (p = 7.9 * 10-4 , OR = 0.45, 95%CI = 0.27-0.74),
      whereas the minor allele (C) was associated with susceptibility to hip OA (p =
      7.9 * 10-4 , OR = 2.24, 95%CI = 1.35-3.72). The genotype T/T was associated with
      the protection to hip OA (p = 3.9 * 10-4 , OR = 0.41, 95%CI = 0.24-0.70), and,
      lastly, the genotype T/C was associated with the higher risk to acquiring hip OA
      (p = 2.6 * 10-4 , OR = 2.50, 95%CI = 1.47-4.25). TLR10 SNP rs11096957 was found
      significantly associated with predisposition to hip OA (p = 0.04, OR = 1.41,
      95%CI = 1.02-1.94) but not knee OA. Our findings suggest that hip OA in Croatian
      population might have a different genetic risk regarding the IL17 and TLR10 gene
      locus than knee OA. (c) 2017 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 36:1684-1693, 2018.

PMID- 29194749
TI  - Longitudinal Effects of Teriparatide or Zoledronic Acid on Bone Modeling- and
      Remodeling-Based Formation in the SHOTZ Study.
AB  - Previously, we reported on bone histomorphometry, biochemical markers, and bone
      mineral density distribution after 6 and 24 months of treatment with teriparatide
      (TPTD) or zoledronic acid (ZOL) in the SHOTZ study. The study included a 12-month
      primary study period, with treatment (TPTD 20 MUg/d by subcutaneous injection or
      ZOL 5 mg/yr by intravenous infusion) randomized and double-blind until the month
      6 biopsy (TPTD, n = 28; ZOL, n = 30 evaluable), then open-label, with an optional
      12-month extension receiving the original treatment. A second biopsy (TPTD, n =
      10; ZOL, n = 9) was collected from the contralateral side at month 24. Here we
      present data on remodeling-based bone formation (RBF), modeling-based bone
      formation (MBF), and overflow modeling-based bone formation (oMBF, modeling
      overflow adjacent to RBF sites) in the cancellous, endocortical, and periosteal
      envelopes. RBF was significantly greater after TPTD versus ZOL in all envelopes
      at 6 and 24 months, except the periosteal envelope at 24 months. MBF was
      significantly greater with TPTD in all envelopes at 6 months but not at 24
      months. oMBF was significantly greater at 6 months in the cancellous and
      endocortical envelopes with TPTD, with no significant differences at 24 months.
      At 6 months, total bone formation surface was also significantly greater in each
      envelope with TPTD treatment (all p < 0.001). For within-group comparisons from 6
      to 24 months, no statistically significant changes were observed in RBF, MBF, or
      oMBF in any envelope for either the TPTD or ZOL treatment groups. Overall, TPTD
      treatment was associated with greater bone formation than ZOL. Taken together the
      data support the view that ZOL is a traditional antiremodeling agent, wheareas
      TPTD is a proremodeling anabolic agent that increases bone formation, especially
      that associated with bone remodeling, including related overflow modeling, with
      substantial modeling-based bone formation early in the course of treatment. (c)
      2017 American Society for Bone and Mineral Research.

PMID- 29194750
TI  - How Basic Science Discoveries Have Shaped the Treatment of Bone and Mineral
      Disorders.

PMID- 29194751
TI  - Reply to: Macrophages Driving Heterotopic Ossification: Convergence of
      Genetically-Driven and Trauma-Driven Mechanisms.

PMID- 29194752
TI  - The Regulatory Role of the Oral Commensal Streptococcus mitis on Human Monocytes.
AB  - Streptococcus mitis colonizes all niches of the human oral cavity from early
      infancy and throughout life. Monocytes patrol blood vessels, lymphoid and non
      lymphoid tissues and migrate into infected tissue where they participate in the
      inflammatory cascade and immune regulation. Here, we studied the effect of S.
      mitis on monocytes. Transcriptome analysis of monocytes exposed to S. mitis
      (SmMo) revealed increased transcription of chemotactic factors (CCL2, CCL3,
      CCL20, CXCL1, CXCL2) and cytokines (IL1A, IL1B, IL6, IL23, IL36G, TNF),
      indicating that S. mitis may trigger recruitment of leucocytes and initiate
      inflammation. Increased transcription in SmMo of IL1B, IL6 and IL23 indicated
      that S. mitis may participate in the induction of Th17 responses and agreed with
      our earlier findings of S. mitis-mediated memory Th17 reactivity. Furthermore, S.
      mitis inhibited tetanus toxoid-specific CD4 T cell proliferation. This can be due
      to the increased secretion of IL-10 and expression of PD-L1 that was observed in
      SmMo. PGE2 can modulate IL-10 and PD-L1 expression, concomitant with that of
      CCR7, IL-12 and IL-23 that also were changed. This, along with increased SmMo
      transcription of PTGS2 (COX2) and PTGER4 (EP4), pointed to a role of PGE2.
      Measurement of PGE2 secretion by SmMo showed indeed a marked increase, and
      chemical inhibition of PGE2 production lowered the PD-L1 expression on SmMo. In
      conclusion, our findings show that S. mitis may trigger immune modulation by
      recruiting immune cells to the site of infection, while at the same time
      dampening the severity of the response through expression of IL-10, PGE2 and PD
      L1.

PMID- 29194753
TI  - Immunogenicity of recombinant measles vaccine expressing fusion protein of
      respiratory syncytial virus in cynomolgus monkeys.
AB  - Respiratory syncytial virus (RSV) is a common cause of respiratory infections in
      infants. Effective vaccines are currently being sought, but no vaccine is thus
      far available. In our previous study, recombinant AIK-C measles vaccine
      expressing the RSV fusion protein (MVAIK/RSV/F) was developed and protective
      immunity against RSV demonstrated in cotton rats. In the present study, the
      immunogenicity and protective effects were investigated in three cynomolgus
      monkeys immunized with MVAIK/RSV/F. Neutralizing test antibodies against RSV were
      detected and no infectious virus was recovered from the lungs of monkeys
      immunized with MVAIK/RSV/F after challenge. MVAIK/RSV/F has the potential to
      inhibit RSV infection.

PMID- 29194754
TI  - The mechanism of nucleotide-binding domain dimerization in the intact maltose
      transporter as studied by all-atom molecular dynamics simulations.
AB  - The Escherichia coli maltose transporter MalFGK2 -E belongs to the protein
      superfamily of ATP-binding cassette (ABC) transporters. This protein is composed
      of heterodimeric transmembrane domains (TMDs) MalF and MalG, and the homodimeric
      nucleotide-binding domains (NBDs) MalK2 . In addition to the TMDs and NBDs, the
      periplasmic maltose binding protein MalE captures maltose and shuttle it to the
      transporter. In this study, we performed all-atom molecular dynamics (MD)
      simulations on the maltose transporter and found that both the binding of MalE to
      the periplasmic side of the TMDs and binding of ATP to the MalK2 are necessary to
      facilitate the conformational change from the inward-facing state to the occluded
      state, in which MalK2 is completely dimerized. MalE binding suppressed the
      fluctuation of the TMDs and MalF periplasmic region (MalF-P2), and thus prevented
      the incorrect arrangement of the MalF C-terminal (TM8) helix. Without MalE
      binding, the MalF TM8 helix showed a tendency to intrude into the substrate
      translocation pathway, hindering the closure of the MalK2 . This observation is
      consistent with previous mutagenesis experimental results on MalF and provides a
      new point of view regarding the understanding of the substrate translocation
      mechanism of the maltose transporter.

PMID- 29194755
TI  - Boron neutron capture therapy using reactor epithermal neutron beams could
      effectively control in-transit and lymph node metastases originating from a
      cutaneous malignant melanoma.

PMID- 29194756
TI  - A higher level of ketonaemia does not predict oral rehydration failure in
      vomiting paediatric patients and routine measurement is unnecessary.
AB  - AIM: This study determined if blood levels of beta-hydroxybutyrate were
      associated with the rate of failure in oral rehydration in paediatric patients
      with vomiting. METHODS: This was a prospective observational study that was
      carried out from December 1, 2015 to November 30, 2016 in the Rio Hortega
      University Hospital, Valladolid, Spain. The study cohort were patients up to 14
      years old who attended the emergency department with three or more vomiting
      episodes in the last four hours and glycaemia higher than 45 mg/dL. Blood was
      measured for beta-hydroxybutyrate levels prior to the administration of oral
      rehydration solution for 90 minutes. Two or more vomiting episodes during this
      period were considered failed oral rehydration. RESULTS: We analysed 248
      patients, with a median age of four years and 7.5 months and 233 (94%) of the
      parents took part. The median number of vomiting episodes in the previous four
      hours was five and oral rehydration was successful in 183 (78.5%) patients. The
      multivariate analysis showed that the initial beta-hydroxybutyrate blood level
      was not associated with the failure of oral rehydration. CONCLUSION: Blood levels
      of beta-hydroxybutyrate had no predictive value for oral rehydration failure in
      young patients with vomiting and this routine measurement is unnecessary.

PMID- 29194757
TI  - Response to Renz and Diaz "The impact of adult-to-adult living donor liver
      transplantation on transplant center outcomes reporting".

PMID- 29194758
TI  - Utility of transthoracic needle biopsy after lung transplantation.
AB  - The purpose of this study was to assess the diagnostic yield and complications of
      CT-guided transthoracic needle biopsy (TTNB) after lung transplantation. A
      database search identified all TTNB performed in lung transplant patients over a
      14-year period. Forty-two biopsies in transplant patients (transplant group) were
      identified and matched to the next biopsy performed in native lungs by the same
      operator (nontransplant group) as a control. Primary outcomes recorded were
      diagnosis, diagnostic yield, pneumothorax requiring intervention, and symptomatic
      pulmonary hemorrhage. Biopsy outcomes were classified as diagnostic, not
      specifically diagnostic, and nondiagnostic. Patients in the transplant group were
      younger (P < .002). Emphysema along the biopsy trajectory was more commonly seen
      in the nontransplant group (P < .0006). Needle gauge, size of lesion, pleural
      punctures, lesion depth, and number of passes were not significantly different.
      Diagnostic yield was 71% in the transplant group and 91% in the nontransplant
      group. There were 20 of 42 (48%) malignant nodules in the transplant group
      compared to 31 of 44 (70%) nodules in the nontransplant group (P = .05). There
      were no complications in the transplant group. The nontransplant group had two
      pneumothoraces requiring intervention. TTNB after lung transplant is safe with a
      moderate diagnostic yield. Nonmalignant lesions are more common after lung
      transplantation.

PMID- 29194759
TI  - Association between urine retinol-binding protein levels and nonalcoholic fatty
      liver disease: A cross-sectional study in Chinese population.
AB  - OBJECTIVE: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been
      rapidly increased, becoming a public health problem worldwide. Our objective was
      to investigate the association between urine retinol-binding protein (RBP) and
      NAFLD in a Chinese population and develop a multivariate logistic regression
      model for NAFLD prediction. METHODS: A total of 317 NAFLD patients and 391
      healthy controls were enrolled in this cross-sectional study based on inclusion
      and exclusion criteria, from whom fasting urine and blood were collected for
      further study. Urine RBP level and other parameters were measured and compared
      between NAFLD subjects and controls. RESULTS: Urine RBP levels (expressed by
      RBP/creatinine ratio) in NAFLD patients were significantly higher than controls
      (median 133.1 mg/g vs 110.7 mg/g; P < .001). Urine RBP/creatinine ratio was
      verified as an independent factor for NAFLD prediction after adjustment in
      multivariate logistic regression. The area under curve (AUC) of receiver
      operating characteristic (ROC) was 0.889 with the 95% confidence interval from
      0.867 to 0.912.With a cutoff point of 0.215, the sensitivity and specificity of
      urine RBP/creatinine ratio in NAFLD prediction were 81.1% and 84.5%,
      respectively. CONCLUSION: Our results demonstrated that urine RBP/creatinine
      ratio was an independent risk factor for NAFLD while the predictive model for
      NAFLD diagnosis is noninvasive with high sensitivity and specificity.

PMID- 29194761
TI  - Development and use of a piggyBac-based jumpstarter system in Drosophila suzukii.
AB  - Spotted wing drosophila, Drosophila suzukii, is an invasive pest that primarily
      attacks fresh, soft-skinned fruit. Although others have reported successful
      integration of marked piggyBac elements into the D. suzukii genome, with a very
      respectable transgenesis rate of ~16%, here we take this work a step further by
      creating D. suzukii jumpstarter strains. These were generated through integration
      of a fluorescent-marked Minos element carrying a heat shock protein 70-driven
      piggyBac transposase gene. We demonstrate that there is a dramatic increase in
      transformation rates when germline transformation is performed in a transposase
      expressing background. For example, we achieved transformation rates as high as
      80% when microinjecting piggyBac-based plasmids into embryos derived from one of
      these D. suzukii jumpstarter strains. We also investigate the effect of insert
      size on transformation efficiency by testing the ability of the most efficient
      jumpstarter strain to catalyze integration of differently-sized piggyBac
      elements. Finally, we demonstrate the ability of a jumpstarter strain to
      remobilize an already-integrated piggyBac element to a new location,
      demonstrating that our jumpstarter strains could be used in conjunction with a
      piggyBac-based donor strain for genome-wide mutagenesis of D. suzukii.

PMID- 29194762
TI  - Cholinesterase levels predict exercise capacity in cardiac recipients early after
      transplantation.
AB  - PURPOSE: Although cardiac rehabilitation is recommended for patients early after
      heart transplantation (HTx), adequate exercise effect cannot always be obtained,
      partly because in patients with chronic heart failure, exercise capacity is
      reduced due to malnutrition while waiting for HTx. This study aimed to
      investigate the relationships between exercise capacity and clinical variables,
      including nutritional indicators, early after HTx. PATIENTS AND METHODS: Forty
      three HTx recipients were studied. The mean age at HTx was 38 +/- 14 years, and
      86% were male. We assessed the relationships between peak oxygen uptake (VO2 )
      and clinical variables, including plasma B-type natriuretic peptide (BNP),
      isometric knee extensor muscle strength (KEMS), and nutritional indicators within
      1 week of their respective discharges. RESULTS: Peak VO2 correlated positively
      with isometric KEMS (r = .63, P < .0001) and negatively with BNP level (r = -.37,
      P = .015). Of the nutritional indicators, only cholinesterase levels had a
      significant relationship with peak VO2 (r = .34, P = .028), whereas the Geriatric
      Nutritional Risk Index and the Controlling Nutritional Status scores did not. In
      multiple linear regression analysis, cholinesterase levels and isometric KEMS
      were independent predictors of peak VO2 . CONCLUSION: Cholinesterase levels
      predicted exercise capacity early after HTx.

PMID- 29194763
TI  - Posttraumatic Stress, Somatization, and Quality of Life Among Ivorian Refugees.
AB  - The present study examined the relationship between peritraumatic reactions,
      posttraumatic stress disorder (PTSD) symptoms, somatization, and quality of life
      (QoL) in a sample of refugees, two years after the 2011 Ivory Coast
      sociopolitical crisis. Participants were 101 Ivorian adult refugees (mean age =
      31.61 years, SD = 7.84; 45.5% women) who completed several questionnaires
      relating to peritraumatic reactions, PTSD symptoms, somatization, and QoL. Most
      participants (86.1%) scored above the cutoff for probable PTSD. Peritraumatic
      dissociation and peritraumatic distress were significantly associated with PTSD
      symptoms, (r = .64, p < .001) and (r = .60, p < .001), respectively, and
      somatization, (r = .21, p = .038) and (r = .35, p < .001), respectively, as well
      as with QoL, (r = -.20, p = .045) and (r = -.21, p = .037), respectively.
      Similarly, QoL was significantly negatively correlated with PTSD symptoms (r = 
      .33, p < .001) and somatization (r = -.39, p < .001). In multivariate analyses,
      somatization was the strongest predictor of QoL (beta = -.31, p = .003). Finally,
      somatization statistically mediated the association between peritraumatic
      distress and QoL. These findings suggest that PTSD may be frequent among Ivorian
      refugees, and that somatization may be an important feature of the traumatic
      experiences. Targeting somatization in conjunction with trauma-centered therapy
      may improve outcomes in sub-Saharan Africans with PTSD.

PMID- 29194760
TI  - Hepatic Fibrosis in Dogs.
AB  - Hepatic fibrosis is commonly diagnosed in dogs, often as a sequela to chronic
      hepatitis (CH). The development of fibrosis is a crucial event in the progression
      of hepatic disease that is of prognostic value. The pathophysiology of hepatic
      fibrosis in human patients and rodent models has been studied extensively.
      Although less is known about this process in dogs, evidence suggests that
      fibrogenic mechanisms are similar between species and that activation of hepatic
      stellate cells is a key step. Diagnosis and staging of hepatic fibrosis in dogs
      requires histopathological examination of a liver biopsy specimen. However,
      performing a liver biopsy is invasive and assessment of fibrotic stage is
      complicated by the absence of a universally accepted staging scheme in veterinary
      medicine. Serum biomarkers that can discriminate among different fibrosis stages
      are used in human patients, but such markers must be more completely evaluated in
      dogs before clinical use. When successful treatment of its underlying cause is
      feasible, reversal of hepatic fibrosis has been shown to be possible in rodent
      models and human patients. Reversal of fibrosis has not been well documented in
      dogs, but successful treatment of CH is possible. In human medicine, better
      understanding of the pathomechanisms of hepatic fibrosis is leading to the
      development of novel treatment strategies. In time, these may be applied to dogs.
      This article comparatively reviews the pathogenesis of hepatic fibrosis, its
      diagnosis, and its treatment in dogs.

PMID- 29194764
TI  - A comparative study found that a seven-year school-based exercise programme
      increased physical activity levels in both sexes.
AB  - AIM: This study assessed whether a Swedish school-based exercise intervention
      programme could increase total physical activity. METHODS: We followed up 228
      children who started school in 1998-2000 seven years later, when they had reached
      a mean age of 14.8. The 152 children (59% boys) at the intervention school did
      200 minutes of physical education per week during that period, and the 76
      children (50% boys) in the three control schools did the standard 60 minutes.
      Questionnaires assessed the durations of total and leisure-time physical activity
      and screen-time activity at baseline and after five and seven years. RESULTS:
      Physical activity and screen-time activity were similar between the two groups
      before the study started. The intervention group then achieved higher durations
      of total physical activity than the controls (p < 0.001) and these levels
      remained in the sex-specific evaluations. There were no differences between the
      groups in the durations of leisure-time activity (p 0.08-0.77) or screen-time
      activity (p 0.31-0.91). CONCLUSION: A school-based exercise intervention
      programme increased the total duration of physical activity in both sexes without
      any compensatory increase in screen-time activity. The findings contradict the
      activity-stat theory, which stated that the duration of physical activity in
      children is constant.

PMID- 29194765
TI  - c-Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors
      in Dogs Treated with Prednisone and Toceranib or Vinblastine.
AB  - BACKGROUND: KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have
      not been prospectively compared in the treatment of macroscopic mast cell tumors
      (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT
      without c-kit mutations. HYPOTHESIS/OBJECTIVES: To determine the value of KIT
      genotyping and localization in treatment decisions for dogs with macroscopic MCT.
      We hypothesized that c-kit mutated MCT would have a better response to TOC than
      VBL. ANIMALS: Eighty-eight client-owned dogs with macroscopic MCT. METHODS:
      Prospective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or
      VBL (2.5 mg/m2 weekly * 4 then EOW) by KIT localization and c-kit mutation status
      using an adaptive randomization scheme. RESULTS: Sixty dogs were allocated to TOC
      and 28 to VBL. Of the dogs receiving TOC, 20% had c-kit mutations, compared to
      30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL)
      (odds ratio = 1.56 [0.62-3.92]; P = 0.28). Median progression-free survival (PFS)
      for dogs receiving VBL was 78 days (7-1,521) and for TOC 95.5 (14-990); hazard
      ratio (HR) = 1.34 [0.72-2.50]; P = 0.36. Median overall survival (OS) was 241.5
      days (10-1,521) for the VBL group and 159 (20-990) for the TOC group; HR = 0.80
      ([0.45-1.41]; P = 0.44). CONCLUSIONS AND CLINICAL IMPORTANCE: Neither PFS nor OS
      was significantly different between treatment groups. As the proportion of dogs
      with c-kit mutations was not different between treatment groups in this
      population of dogs, c-kit mutation status did not predict treatment response.

PMID- 29194767
TI  - Evolution of lung and kidney allograft function in patients receiving kidney
      after lung transplantation.
AB  - Calcineurin inhibitor (CNI) toxicity leads to end-stage renal disease in almost
      half of long-term survivors after lung transplantation, some of them receiving
      kidney transplants. Little is known about the outcomes of kidney and lung
      allograft function following kidney after lung transplantation (KALTPL) in the
      modern era. We retrospectively analyzed a group of 13 consecutive patients who
      received a KALTPL with respect to their renal and pulmonary function and
      immunological evolution over 2 years. We documented a stable evolution of forced
      expiratory volume in 1 second (FEV1) after KALTPL in most patients as well as an
      excellent kidney graft during the 2-year follow-up period. In our small cohort,
      living donations showed a significantly higher estimated glomerular filtration
      rate compared to deceased donation (75.7 compared to 41.6 mL/min). Patients who
      received a preemptive KALTPL were more likely to improve their lung function
      after KALTPL. Four patients developed de novo donor-specific antibodies (DSA)
      against the kidney graft. There were no DSA against shared antigens from the lung
      allograft. De novo DSA did not lead to graft loss in any patient. All 13 patients
      survived the first 24 months after KALTPL.

PMID- 29194766
TI  - Absence Seizures as a Feature of Juvenile Myoclonic Epilepsy in Rhodesian
      Ridgeback Dogs.
AB  - Myoclonic epilepsy in Rhodesian Ridgeback (RR) dogs is characterized by myoclonic
      seizures occurring mainly during relaxation periods, a juvenile age of onset and
      generalized tonic-clonic seizures in one-third of patients. An 8-month-old female
      intact RR was presented for myoclonic seizures and staring episodes that both
      started at 10 weeks of age. Testing for the DIRAS1 variant indicated a homozygous
      mutant genotype. Unsedated wireless video-electroencephalography (EEG) identified
      frequent, bilaterally synchronous, generalized 4 Hz spike-and-wave complexes
      (SWC) during the staring episodes in addition to the characteristic myoclonic
      seizures with generalized 4-5 Hz SWC or 4-5 Hz slowing. Photic stimulation did
      not evoke a photoparoxysmal response. Repeat video-EEG 2 months after initiation
      of levetiracetam treatment disclosed a >95% decrease in frequency of myoclonic
      seizures, and absence seizures were no longer evident. Absence seizures represent
      another seizure type in juvenile myoclonic epilepsy (JME) in RR dogs, which
      reinforces its parallels to JME in humans.

PMID- 29194768
TI  - Jeffrey Lima Hayes O'Riordan: March 27, 1931 - October 9, 2017.

PMID- 29194769
TI  - Intravascular ultrasound of the proximal left anterior descending artery is
      sufficient to detect early cardiac allograft vasculopathy.
AB  - OBJECTIVE: Cardiac allograft vasculopathy (CAV) can be detected early with
      intravascular ultrasound (IVUS), but there is limited information on the most
      efficient imaging protocol. METHODS: Coronary angiography and IVUS of the three
      coronary arteries were performed. Volumetric IVUS analysis was performed, and a
      Stanford grade determined for each vessel. RESULTS: Eighteen patients were
      included 18 (range 12-24) months after transplantation. Angiographic CAV severity
      ranged from none (CAV0) to mild (CAV1), whereas IVUS CAV severity ranged from
      none (Stanford grade I) to severe (grade IV). Maximal intimal thickness measured
      with IVUS was significantly greater in the LAD (0.84 +/- 0.48 mm) than in the LCX
      (0.46 +/- 0.32 mm) or the RCA (0.53 +/- 0.41 mm, P = .005). Diagnostic accuracy
      of IVUS in the left anterior descending artery was 100% (18 of 18 Stanford grades
      matched the patient's highest overall Stanford grade), 66% in the right coronary
      artery (12 of 18), and 56% in the left circumflex artery (11 of 18). The minimal
      required length of left anterior descending artery pullbacks to attain 100%
      accuracy was 36 mm (range 3-36 mm) distal from the guide catheter ostium.
      CONCLUSIONS: These data suggest that focal IVUS imaging of the proximal LAD
      followed by volumetric analysis may suffice when screening for transplant
      vasculopathy.

PMID- 29194771
TI  - Outcomes of indwelling metallic stents for malignant extrinsic ureteral
      obstruction.
AB  - OBJECTIVES: To report the treatment outcomes of patients with extrinsic ureteral
      obstruction treated with metallic stents and to identify the factors predicting
      stent failure. METHODS: A total of 52 patients with extrinsic ureteral
      obstruction as a result of malignancy (66 ureters) were treated with metallic
      stents (Resonance(r) ) and included in the study. The median observation period
      was 118 days. RESULTS: The median survival time of these patients was 210 days,
      and the stent patency rate was 86.0% at 6 months and 60.0% at 1 year. Eight
      (15.4%) patients underwent nephrostomy as a result of stent failure. The
      occlusion rate of bilateral ureteral obstructed cases was significantly higher
      than that of unilateral cases. There was no correlation between the preoperative
      serum creatinine level, causes of ureteral occlusions (compression by tumor,
      lymph node metastasis, peritoneal dissemination), obstructed site (upper, middle,
      lower ureter) and stent failure. CONCLUSIONS: Metallic stents are excellent in
      maintaining patency compared with the conventional stents. Therefore, they can be
      used as first-line treatment of malignant ureteral obstructions.

PMID- 29194770
TI  - Differences in Epidural Pathology between Cervical and Thoracolumbar
      Intervertebral Disk Extrusions in Dogs.
AB  - BACKGROUND: Although the basic pathophysiology is the same in both cervical and
      thoracolumbar intervertebral disk (IVD) extrusions, there are considerable
      clinical differences that have only been partially explained.
      HYPOTHESIS/OBJECTIVES: The epidural inflammatory response differs between
      cervical and thoracolumbar IVD extrusions. ANIMALS: Fifty-five dogs with cervical
      and 80 dogs with thoracolumbar IVD extrusions. METHODS: Clinical data and
      histopathologic variables were investigated. Associations between severity of
      epidural inflammation and clinical and pathologic variables, impact of
      chondrodystrophic phenotype, and localization (cervical versus thoracolumbar)
      were evaluated statistically. RESULTS: Dogs with cervical IVD extrusion were
      significantly older (P < 0.001), had less severe and longer duration of
      neurologic signs (both P < 0.001), were more painful (P = 0.038), and had a
      better outcome (P = 0.005) than dogs with a thoracolumbar IVD extrusion. On
      histopathology, cervical epidural material had less severe calcification (P =
      0.002) and inflammation (P < 0.001). No significant differences regarding
      chondrodystrophic phenotype were found. CONCLUSION AND CLINICAL IMPORTANCE: There
      was significantly less intensive inflammatory response in the cervical epidural
      space. This observation correlated positively with less nucleus pulposus
      calcification in cervical extrusions indicating biochemical, metabolic, and
      biomechanical differences between the 2 locations, which remain to be
      characterized in future studies.

PMID- 29194772
TI  - Comparison of Multiplate, Platelet Function Analyzer-200, and Plateletworks in
      Healthy Dogs Treated with Aspirin and Clopidogrel.
AB  - BACKGROUND: Platelet function testing may be warranted to assess response to
      aspirin and clopidogrel. HYPOTHESIS/OBJECTIVES: To evaluate the effects of
      aspirin, clopidogrel, or combination therapy using 3 platelet function tests:
      Multiplate Analyzer (MP), Platelet Function Analyzer-200 (PFA), and Plateletworks
      (PW). ANIMALS: Six healthy laboratory Beagles. METHODS: Randomized double-blind
      placebo-controlled study (crossover design). Dogs were given aspirin 1 mg/kg,
      clopidogrel 2 mg/kg, or combination therapy for 1 week each, with a washout
      period of 2 weeks. Platelet function was assessed on days 0 and 7 of each phase
      using MP (adenosine diphosphate [ADP], arachidonic acid [AA], collagen [COL]
      agonists), PFA (P2Y, COL-ADP [CADP], COL-Epinephrine [CEPI] cartridges), and PW
      (ADP, AA, COL agonists). Platelet counts were obtained with impedance and optical
      counters. RESULTS: For MP, mean aggregation was decreased for COL and AA with
      combination therapy and for ADP with all treatments. For PFA, mean CT was
      increased for the CEPI cartridge with aspirin; and for the P2Y and CADP
      cartridges with clopidogrel or combination therapy. More dogs receiving
      clopidogrel showed an increase in PFA CT using the P2Y than the CADP cartridge.
      For PW, mean aggregation was decreased for AA with all treatments; for ADP with
      clopidogrel or combination therapy; and for COL with clopidogrel. The PW results
      with the 2 hematology counters showed almost perfect agreement. CONCLUSION AND
      CLINICAL IMPORTANCE: All platelet function tests detected treatment effects in
      some dogs and may have utility for monitoring therapy.

PMID- 29194773
TI  - Plasma IL-8 signature correlates with pain and depressive symptomatology in
      patients with burning mouth syndrome: Results from a pilot study.
AB  - BACKGROUND: Burning mouth syndrome (BMS) is a neuropathic orofacial pain
      condition of unknown aetiology that encompasses intra-oral burning pain without
      abnormal clinical findings. Psychological, neural and inflammatory processes are
      associated with BMS pathogenesis. Currently, studies characterising plasma
      cytokine/chemokine profiles with pain and depression in patients with BMS are
      lacking. Considering that inflammation is associated with the pathophysiology of
      BMS, and that inflammation is closely associated with pain and depression, we
      aimed to correlate depressive symptomatology and oral cavity pain with plasma
      cytokine/chemokine signatures in a cohort of patients with BMS. METHODS: In this
      study, plasma protein levels of Th1 cytokines (IFN-gamma, IL-2, IL-12p70, TNF
      alpha), Th2 cytokines (IL-4, IL-10, IL-6, IL-13) and the chemokine IL-8 were
      assessed in patients with BMS (n = 10) and healthy volunteers (n = 10), using pro
      inflammatory-10-plex assays. Clinical histories, alongside self-rated oral cavity
      pain intensities and depressive symptomatology were assessed using a visual
      analogue scale and the 16-item Quick Inventory of Depressive Symptomatology
      questionnaires, respectively. RESULTS: We present evidence that BMS is associated
      with increased depressive symptomatology and enhanced oral cavity pain. Plasma
      isolated from BMS patients display enhanced expression of the pro-inflammatory
      chemokine IL-8, when compared to plasma from healthy individuals. Plasma IL-8
      signature correlates with pain and depressive symptomatology in the study cohort.
      CONCLUSIONS: Overall, these findings indicate that plasma IL-8 profiles are
      dysregulated in BMS and that modulation of IL-8 production in the disorder may be
      a tool in the management of BMS symptomatology.

PMID- 29194774
TI  - Current clinical algorithms for predicting common bile duct stones have only
      moderate accuracy.
AB  - BACKGROUND AND AIM: A risk-stratified approach for selecting patients likely to
      harbor common bile duct (CBD) stones to proceed directly to endoscopic or
      surgical stone clearance, rather than undergo less invasive testing, has been
      proposed. We assessed the performance of three clinical algorithms used to
      predict CBD stones. METHODS: All patients undergoing first-time endoscopic
      retrograde cholangiopancreatography (ERCP) in 2011-2012 as a result of suspected
      CBD stones were enrolled prospectively in a clinical database. Data such as
      imaging test findings and liver function tests (LFTs) were collected 48 h prior
      to and on the day of ERCP. Patients were stratified into different risk groups
      for harboring CBD stones according to three clinical algorithms using imaging and
      laboratory data. Findings on ERCP were used as gold standard. Performance
      characteristics of each algorithm were separately calculated for each time point
      of LFT assessment. RESULTS: Overall, 186 patients were analyzed, 75% of whom
      presented CBD stones on ERCP. Proportion of patients categorized as high-risk for
      harboring CBD stones varied among the three algorithms (67% vs 73% vs 56%). Also,
      the algorithms showed only moderate, albeit comparable, accuracy for predicting
      the presence of CBD stones (0.65, 95% confidence interval [CI] 0.62-0.68 vs 0.68,
      95% CI 0.63-0.67 vs 0.59, 95% CI 0.57-0.61). Similar results were obtained when
      performance characteristics were recalculated using LFT from 48 h prior to ERCP
      (data not shown). CONCLUSION: Three diagnostic algorithms commonly used for
      predicting CBD stones have comparable but only moderate accuracy. Further
      research is warranted to improve risk stratification of patients with suspected
      CBD stones.

PMID- 29194775
TI  - Involvement of shared mucosal-associated microbiota in the duodenum and rectum in
      diarrhea-predominant irritable bowel syndrome.
AB  - BACKGROUND AND AIM: Most studies of diarrhea-predominant irritable bowel syndrome
      (IBS-D) focused on microbiota dysbiosis in a single segment of the intestine such
      as the colon. However, the intestine as a whole is involved in IBS-D and
      knowledge about the role of microbiota shared by the duodenum and rectum in IBS-D
      is limited. Here, we investigated the characteristics of mucosal microbiota
      shared by the duodenum and rectum in IBS-D patients. METHODS: We collected
      duodenal and rectal mucosal samples from 33 adult IBS-D patients and 15 healthy
      control (HC) subjects. The 454 pyrosequencing method and multiple bioinformatics
      analyses were used to examine bacterial 16S rRNA. Clinical data including
      symptoms and Bristol Stool Form were analyzed. RESULTS: Mucosal microbiota in
      duodenal samples differed from rectal samples in HC, while less difference was
      shown in IBS-D. More numbers in terms of shared operational taxonomic units and
      genera found in IBS-D compared with HC. The frequency of genera in the duodenum
      and rectum of HC differed from that of IBS-D. We identified 24 genera shared in
      the duodenum and rectum, which both changed dramatically in IBS-D. Among these 24
      genera, half had similar trends in frequency differences, and the other half had
      opposite trends. The frequency of Faecalibacterium and Hyphomicrobium were
      associated with clinical data of IBS-D patients. CONCLUSIONS: Shared mucosal
      associated microbiota in the duodenum and rectum appear to contribute to the
      etiology and pathophysiology of whole intestine of IBS-D and to be potential
      therapeutic targets.

PMID- 29194776
TI  - Endosymbiosis and its significance in dermatology.
AB  - Proposed at the beginning of the twentieth century to explain the origin of
      eukaryotic organelles from prokaryotes, endosymbiosis is now medically defined by
      various interaction patterns between microorganisms and their residing hosts,
      best exemplified by the bacterial endosymbiont Wolbachia identified in arthropods
      and filarial nematodes, which can influence normal development, reproduction,
      survival and transmission of the hosts. Based on the transmission modes, vertical
      or horizontal, and the function of the endosymbionts, the host-symbiont
      dependence can be divided into primary or secondary. In dermatology, the role of
      endosymbionts in skin ectoparasitosis has aroused great interests in the past
      years. Riesia pediculicola is a primary bacterial endosymbiont in body lice
      Pediculus humanus, and supplement their hosts with vitamin B, especially
      pantothenic acid. In cimicosis, the Gram-negative Wolbachia can synthesize biotin
      and riboflavin, which are crucial for the growth and reproduction of the bedbug
      Cimex lectularius. In human demodicosis and rosacea, further study is required to
      prove the pathogenic role of the Gram-negative bacteria Bacillus oleronius or the
      Gram-positive bacteria Bacillus cereus demonstrated in the Demodex mites. The
      high infection rate of adult female ticks Ixodes ricinus with the Gram-negative
      bacteria Midichloria mitochondrii present in the mitochondria in diverse ovarian
      cells, with the high seroprevalence rate in tick-exposed subjects, raises the
      possibility that this non-pathogenic endosymbiont may play a role in immune
      response and successful transmission of the tick-borne pathogen. The anaerobic
      protozoan Trichomonas vaginalis and bacteria Mycoplasma hominis are two obligate
      parasites in the urogenital epithelium, with partially overlapping symptoms.
      Intracellular localization of Mycoplasma hominis can avoid host immune response
      and penetration of antibiotics, while Trichomonas vaginalis infected with
      Mycoplasma hominis seems to have a higher cytopathic activity and amoeboid
      transformation rate. Further study on the biology and pathogenesis of different
      endosymbionts in dermatological parasitosis will help for the development of new
      treatment modalities.

PMID- 29194777
TI  - Thermodynamics and Kinetics of Sulfur Cathode during Discharge in MgTFSI2 -DME
      Electrolyte.
AB  - Rechargeable magnesium/sulfur battery is of significant interest because its
      energy density (1700 Wh kg-1 and 3200 Wh L-1 ) is among the highest of all
      battery chemistries (lower than Li/O2 and Mg/O2 but comparable to Li/S), and Mg
      metal allows reversible operation (100% Coulombic efficiency) with no dendrite
      formation. This great promise is already justified in some early reports.
      However, lack of mechanistic study of sulfur reaction in the Mg cation
      environment has severely hindered our understanding and prevents effective
      measures for performance improvement. In this work, the very first systematic
      fundamental study on Mg/S system is conducted by combining experimental methods
      with computational approach. The thermodynamics and reaction pathway of sulfur
      cathode in MgTFSI2 -DME electrolyte, as well as the associated kinetics are
      thoroughly investigated. The results here reveal that sulfur undergoes a
      consecutive staging pathway in which the formation and chain-shortening of
      polysulfide occur at early stage accompanied by the dissolution of long-chain
      polysulfide, and solid-state transition from short-chain polysulfide to magnesium
      sulfide occurs at late stage. The former process is much faster than the latter
      due to the synergetic effect of the mediating effect of dissolved polysulfide and
      the fast diffusion of Mg ion in the amorphous intermediate.

PMID- 29194778
TI  - A historical perspective on milestones in multiple myeloma research.
AB  - The first well-documented case of multiple myeloma was reported in 1844 by Samuel
      Solly. In this article, the author presents a historical review of the disease.
      In particular, the review is focused on the main steps, including the definition
      of Bence Jones proteinuria, the characterization of tumoral plasma cells and
      serum globulins, and the fundamental contribution of Jan Waldenstrom. Finally,
      treatment of multiple myeloma, as well as the development of new agents, is
      discussed.

PMID- 29194779
TI  - The pathological kinematic patterns of the tarsal complex in stage II adult
      acquired flatfoot deformity.
AB  - The in vivo kinematic characteristics of the tarsal joints during gait stance
      phase were still unclear in adult-acquired foot deformity (AAFD). This study
      included seven healthy subjects (fourteen feet) and twelve stage II AAFD patients
      (fourteen feet). The 3D models of tarsal bones were reconstructed based on CT
      scan. Each subject took standard gait on the single fluoroscopy system.
      Continuous lateral fluoroscopic images were collected. The key postures during
      the stance phase were selected. The 2D-3D registration technique was applied to
      explore the spatial motions of the tarsal joints in 6 degrees of freedom (DOF).
      During the whole stance phase, the AAFD talo-navicular joint (TNJ) exhibited ROM
      of 13+/-6 degrees  in the sagittal plane while the normal subjects showed ROM of
      7+/-3 degrees  (P=0.004). In AAFD, the subtalar joint (STJ) demonstrated 19+/-8
      degrees  and 7+/-3 degrees  of motion in coronal and horizontal plane
      respectively while the normal subjects showed 14+/-4 degrees (p=0.031) and 11+/-3
      degrees (p=0.014) of motion respectively. Additionally STJ of AAFD patients
      showed significantly less dorsiflexion during the weight acceptance and showed
      significantly less external rotation both during the weight acceptance and single
      limb support of stance phase. In conclusion, for stage II AAFD patients, the
      talonavicular joint and the subtalar joint showed hypermobility in
      dorsi/planterflexion and inversion/eversion respectively during the gait stance
      phase while the internal/external rotation of the subtalar joint was reduced. The
      current study improves our understanding of the pathological kinematics of the
      tarsal complex in AAFD patients. Notice should be taken about these tarsal joints
      mobility in AAFD during clinical practice. This article is protected by
      copyright. All rights reserved.

PMID- 29194780
TI  - Black Phosphorus Nanosheets as a Neuroprotective Nanomedicine for
      Neurodegenerative Disorder Therapy.
AB  - Transition-metal dyshomeostasis is recognized as a critical pathogenic factor at
      the onset and progression of neurodegenerative disorder (ND). Excess transition
      metal ions such as Cu2+ can catalyze the generation of cytotoxic reactive oxygen
      species and thereafter induce neuronal cell apoptosis. Exploring new chelating
      agents, which are not only capable of capturing excess redox-active metal, but
      can also cross the blood-brain barrier (BBB), are highly desired for ND therapy.
      Herein, it is demonstrated that 2D black phosphorus (BP) nanosheets can capture
      Cu2+ efficiently and selectively to protect neuronal cells from Cu2+ -induced
      neurotoxicity. Moreover, both in vitro and in vivo studies show that the BBB
      permeability of BP nanosheets is significantly improved under near-infrared laser
      irradiation due to their strong photothermal effect, which overcomes the drawback
      of conventional chelating agents. Furthermore, the excellent biocompatibility and
      stability guarantee the biosafety of BP in future clinical applications.
      Therefore, these features make BP nanosheets have the great potential to work as
      an efficient neuroprotective nanodrug for ND therapy.

PMID- 29194781
TI  - Toward Customized Extracellular Niche Engineering: Progress in Cell-Entrapment
      Technologies.
AB  - The primary aim in tissue engineering is to repair, replace, and regenerate
      dysfunctional tissues to restore homeostasis. Cell delivery for repair and
      regeneration is gaining impetus with our understanding of constructing tissue
      like environments. However, the perpetual challenge is to identify innovative
      materials or re-engineer natural materials to model cell-specific tissue-like 3D
      modules, which can seamlessly integrate and restore functions of the target
      organ. To devise an optimal functional microenvironment, it is essential to
      define how simple is complex enough to trigger tissue regeneration or restore
      cellular function. Here, the purposeful transition of cell immobilization from a
      cytoprotection point of view to that of a cell-instructive approach is examined,
      with advances in the understanding of cell-material interactions in a 3D context,
      and with a view to further application of the knowledge for the development of
      newer and complex hierarchical tissue assemblies for better examination of cell
      behavior and offering customized cell-based therapies for tissue engineering.

PMID- 29194782
TI  - Acral lamellar Ichthyosis - expanding the phenotype of temperature-sensitive
      keratinization disorders.

PMID- 29194783
TI  - Assessing dutasteride-associated sexual dysfunction using the U.S. Food and Drug
      Administration Adverse Event Reporting System.
AB  - BACKGROUND: Incidences of sexual dysfunction due to the use of 5 alpha-reductase
      inhibitors have been suggested. Despite low sexual dysfunction reported in
      clinical trials, an analysis of the U.S. Food and Drug Administration Adverse
      Event Reporting System (FAERS) database revealed a significant disproportionality
      in the reporting of sexual dysfunction with the use of finasteride. Therefore, it
      is likely that a similar relationship with dutasteride may exist. OBJECTIVE: To
      determine whether dutasteride use leads to a higher risk of sexual dysfunction
      compared to a baseline risk for all other drugs using the FAERS database.
      METHODS: A case by non-case disproportionality approach was used whereby a
      reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated.
      Cases of dutasteride-associated sexual dysfunction were compared to a reference
      risk of sexual dysfunction for all other drugs in the database. RESULTS: A
      significant disproportionality in reporting of sexual dysfunction with the use of
      dutasteride was observed. The disproportionality was present for all age ranges
      except for 31-45 years where there were few overall reports of adverse events.
      LIMITATIONS: Adverse events can be underreported, and selection bias is inherent
      in the FAERS. CONCLUSION: Dutasteride use is associated with an increase in
      reports of sexual dysfunction.

PMID- 29194784
TI  - Inflammatory disseminated superficial porokeratosis successfully controlled with
      a combination of topical diclofenac gel and systemic etretinate.

PMID- 29194785
TI  - Molecular basis for immunohistochemical and inflammatory changes during
      progression of gingivitis to periodontitis.
AB  - Two common diseases - gingivitis and periodontitis - affect the periodontium.
      Symptoms of disease entities are used for distinguishing various forms of
      gingivitis and periodontitis. Gingivitis follows a linear and progressive course
      when a healthy individual stops oral care, as shown by the experimental
      gingivitis model. It is not known if and when gingivitis transforms into
      periodontitis. A very limited number of studies present direct evidence regarding
      the histological changes over time and how they correlate to the clinical
      transition from gingivitis to periodontitis. This review focuses on the
      pathological changes that occur during the progression of gingivitis into
      periodontitis through discussing the molecular, cellular and immunohistochemical
      aspects of the inflammatory process. Molecular pathways regulating periodontal
      inflammation also determine the outcomes of disease and healing. Treatment of
      inflammatory diseases, particularly periodontitis in which extensive tissue
      damage could result from the inflammatory process, needs to target full
      restoration of the lost tissues. This can only be accomplished by a thorough
      understanding of the activation and resolution of periodontal disease and of the
      molecular events that occur during these phases.

PMID- 29194786
TI  - Microneedling for the treatment of hair loss?
AB  - Microneedling is a minimally invasive dermatological procedure in which fine
      needles are rolled over the skin to puncture the stratum corneum. This therapy is
      used to induce collagen formation, neovascularization and growth factor
      production of treated areas. It has been used in a wide range of dermatologic
      conditions, including androgenetic alopecia (AGA) and alopecia areata, among
      others. While there are a limited number of studies examining this therapy in the
      use of hair loss, microneedling has been successfully paired with other hair
      growth promoting therapies, such as minoxidil, platelet-rich plasma and topical
      steroids, and shown to stimulate hair follicle growth. It is thought that
      microneedling facilitates penetration of such first-line medications, and this is
      one mechanism by which it promotes hair growth. To date, the area most studied
      and with the most success has been microneedling treatment of AGA. While the
      current evidence does not allow one to conclude superiority of microneedling over
      existing standard therapies for hair loss, microneedling shows some promise in
      improving hair growth, especially in combination with existing techniques. This
      review summarizes the current literature regarding microneedling in the treatment
      of alopecia and calls for further studies to define a standard treatment
      protocol.

PMID- 29194787
TI  - Photonic Crystal Phosphors Integrated on a Blue LED Chip for Efficient White
      Light Generation.
AB  - Following the proof-of-concept experiment in the unit structure level, photonic
      crystal (PhC) phosphors-structurally engineered phosphor materials based on the
      nanophotonics principles-are integrated with a blue light-emitting diode (LED)
      chip to demonstrate a compact and efficient white light source. Red- or green
      emitting CdSe-based colloidal quantum dots (CQDs) are coated on a Si3 N4 thin
      film grating to fabricate PhC phosphors. The underlying PhC structure is designed
      such that the photonic band-edge modes at the zone center (k?? = 0) are tuned to
      the energy of the blue excitation photons. By progressively stacking the PhC
      phosphor plates on a blue LED chip, the blue, green, and red emission intensities
      can be tightly controlled to obtain white light with the desired properties. The
      chromaticity coordinates, (0.332, 0.341), and correlated color temperature, 5500
      K, are obtained from a stack of 3 red and 11 green PhC phosphor plates; in
      contrast, a stack of 5 red and 16 green reference phosphor plates are required to
      generate a similar white light. Overall, the PhC phosphors produce 8% higher
      total emission intensity out of 33% less amount of CQDs than the reference
      phosphors.

PMID- 29194788
TI  - A cross-sectional study of clinical factors associated with acne facial scarring
      in patients with active acne.

PMID- 29194789
TI  - Dermoscopic features and patterns of poromas: a multicentre observational case
      control study conducted by the International Dermoscopy Society.
AB  - BACKGROUND: Poromas are benign cutaneous sweat gland tumours that are challenging
      to identify. The dermoscopic features of poromas are not well characterized.
      OBJECTIVE: To determine the clinical-dermoscopic features of poromas. METHODS:
      Cross-sectional, observational study of 113 poromas and 106 matched control
      lesions from 16 contributors and eight countries. Blinded reviewers evaluated the
      clinical and dermoscopic features present in each clinical and dermoscopic image.
      RESULTS: Poromas were most commonly non-pigmented (85.8%), papules (35.4%) and
      located on non-acral sites (65.5%). In multivariate analysis, dermoscopic
      features associated with poroma included white interlacing areas around vessels
      (OR: 7.9, 95% CI: 1.9-32.5, P = 0.004), yellow structureless areas (OR: 2.5, 95%
      CI: 1.1-6.0, P = 0.04), milky-red globules (OR: 3.9, 95% CI: 1.4-11.1, P = 0.01)
      and poorly visualized vessels (OR: 33.3, 95% CI: 1.9-586.5, P = 0.02). The
      presence of branched vessels with rounded endings was positively associated with
      poromas but did not reach statistical significance (OR: 2.4, 95% CI: 0.8-6.5, P =
      0.10). The presence of any of these five features was associated with a
      sensitivity and specificity of 62.8% and 82.0%, respectively. CONCLUSION: We
      identified dermoscopic features that are specific to the diagnosis of poroma.
      Overall, however, the prevalence of these features was low. Significant clinical
      and dermoscopic variability is a hallmark of these uncommon tumours, which are
      most prevalent on non-acral sites.

PMID- 29194790
TI  - Associations between air pollution, climate factors and outpatient visits for
      eczema in West China Hospital, Chengdu, south-western China: a time series
      analysis.
AB  - BACKGROUND: Eczema is one of the most common inflammatory dermatoses that can be
      provoked as a result of external and internal factors. With dense population and
      rapid economic development of China, air pollution is still a serious problem and
      the prevalence of eczema has been elevating. OBJECTIVE: To determine the
      association and lagged effects between environmental factors and the outpatient
      visits for eczema. METHODS: Data of daily outpatient visits for eczema at the
      clinics of dermatology in West China Hospital within the last 5 years were
      collected. Data of environmental factors of Chengdu during the same period,
      including temperature, relative humidity, barometric pressure, wind speed and air
      pollutants concentrations like sulphur dioxide (SO2 ), nitrogen dioxide (NO2 )
      and particular matter (PM10 ), were gathered. The distributed lag nonlinear model
      was used to statistically examine the relationship between eczema and
      environmental factors and their lagged effects. RESULTS: Correlation analysis
      showed that eczema outpatient visits were positively correlated with the air
      pollutants and were negatively correlated with relative humidity. The barometric
      pressure and wind speed influenced the outpatient visits in association with air
      pollutants. CONCLUSION: This study provides evidence that environmental factors
      like relative humidity and multiple air pollutants influence the incidence and
      prevalence of eczema and have lagged effects.

PMID- 29194791
TI  - Eczema-like fish tank granuloma: a new clinical presentation of Mycobacterium
      marinum infection.

PMID- 29194792
TI  - Mucocutaneous manifestations of inflammatory bowel disease in central China -a
      single-centre study.

PMID- 29194793
TI  - Dry Etching with Nanoparticles: Formation of High Aspect-Ratio Pores and Channels
      Using Magnetic Gold Nanoclusters.
AB  - Methods for generating nanopores in substrates typically involve one or more wet
      etching steps. Here a fundamentally different approach to produce nanopores in
      sheet substrates under dry, ambient conditions, using nanosecond-pulsed laser
      irradiation and magnetic gold nanoclusters (MGNCs) as the etching agents is
      described. Thermoplastic films (50-75 um thickness) are coated with MGNCs then
      exposed to laser pulses with a coaxial magnetic field gradient, resulting in high
      aspect ratio channels with tapered cross sections as characterized by confocal
      fluorescence tomography. The dry-etching process is applicable to a wide variety
      of substrates ranging from fluoropolymers to borosilicate glass, with etch rates
      in excess of 1 um s-1 . Finite-element modeling suggests that the absorption of
      laser pulses by MGNCs can produce temperature spikes of nearly 1000  degrees C,
      which is sufficient for generating photoacoustic responses that can drive
      particles into the medium, guided by magnetomotive force.

PMID- 29194794
TI  - The periodontal pocket.
AB  - Periodontal disease is synonymous with the presence of periodontal pockets, and
      very often the clinical success of periodontal therapy is based on periodontal
      pocket depth reduction. Therefore, in the fields of periodontology and implant
      dentistry, significant research effort has been placed on the etiopathogenesis,
      diagnosis and treatment of periodontal/peri-implant disease and as a consequence
      on pocket pathology. In this volume of Periodontology 2000, the in-depth reviews
      include topics ranging from preclinical models, anatomy and structure of tissues,
      and molecular and bacterial components, to treatments of pockets around teeth and
      implants. These reviews aim to provide the readers with current and future
      perspectives on the different areas of research into the periodontal pocket.

PMID- 29194795
TI  - Description of the periodontal pocket in preclinical models: limitations and
      considerations.
AB  - Establishment of periodontal health and regeneration of the lost periodontal
      tissues are always the ultimate goal of periodontal treatment. The development of
      new therapeutic approaches raises the necessity for appropriate experimental
      models that present periodontal structures and healing capability comparable to
      humans. Preclinical research and extrapolation of the data to human conditions
      remains a stage of great importance before the clinical application of the new
      biomaterials and techniques. Periodontal pockets/defects in preclinical models
      can be induced experimentally through acute or chronic or a combination of both
      (induced) modalities. The features of the created defects and those of humans
      vary greatly mostly due to the nature of the periodontal disease. This is an
      important point to take into account, since it is well recognized that the
      potential of periodontal therapy may be dependent on both the biological
      background and the defect morphology. This review provides insight into the
      commonly used preclinical models for the reproduction of the periodontal pocket
      and discusses the advantages and disadvantages of each model in terms of
      similarity to human conditions, standardization and reproducibility.

PMID- 29194796
TI  - The periodontal pocket: pathogenesis, histopathology and consequences.
AB  - The conversion of junctional epithelium to pocket epithelium is regarded as a
      hallmark in the development of periodontitis. Knowledge of factors contributing
      to the initiation and progression of pocket formation is important and may result
      in the development of better preventive measures and improve healing outcomes
      after therapeutic interventions. The periodontal pocket is a pathologically
      deepened gingival sulcus. In healthy periodontal conditions, the defense
      mechanisms are generally sufficient to control the constant microbiological
      challenge through a normally functioning junctional epithelium and the
      concentrated powerful mass of inflammatory and immune cells and macromolecules
      transmigrating through this epithelium. In contrast, destruction of the
      structural integrity of the junctional epithelium, which includes disruption of
      cell-to-cell contacts and detachment from the tooth surface, consequently leading
      to pocket formation, disequilibrates this delicate defense system. Deepening of
      the pocket apically, and also horizontal expansion of the biofilm on the tooth
      root, puts this system to a grueling test. There is no more this powerful
      concentration of defense cells and macromolecules that are discharged at the
      sulcus bottom and that face a relatively small biofilm surface in the gingival
      sulcus. In a pocket situation, the defense cells and the macromolecules are
      directly discharged into the periodontal pocket and the majority of epithelial
      cells directly face the biofilm. The thinning of the epithelium and its
      ulceration increase the chance for invasion of microorganisms and their products
      into the soft connective tissue and this aggravates the situation. Depending on
      the severity and duration of disease, a vicious circle may develop in the pocket
      environment, which is difficult or impossible to break without therapeutic
      intervention.

PMID- 29194797
TI  - Dental calculus: the calcified biofilm and its role in disease development.
AB  - Dental calculus represents the first fossilized record of bacterial communities
      as a testimony of evolutionary biology. The development of dental calculus is a
      dynamic process that starts with a nonmineralized biofilm which eventually
      calcifies. Nonmineralized dental biofilm entraps particles from the oral cavity,
      including large amounts of oral bacteria, human proteins, viruses and food
      remnants, and preserves their DNA. The process of mineralization involves
      metabolic activities of the bacterial colonies and strengthens the attachment of
      nonmineralized biofilms to the tooth surface. From a clinical point of view,
      dental calculus always harbors a living, nonmineralized biofilm, jeopardizing the
      integrity of the dento-gingival or implanto-mucosal unit. This narrative review
      presents a brief historical overview of dental calculus formation and its
      clinical relevance in modern periodontal practice.

PMID- 29194798
TI  - Efficacy and tolerance of GELOXD/P-GEMOXD in newly diagnosed nasal-type
      extranodal NK/T-cell lymphoma: A multicenter retrospective study.
AB  - OBJECTIVES: Nasal-type extranodal natural killer NK/T-cell lymphoma (ENKTCL) is a
      distinct type of non-Hodgkin lymphoma with poor prognosis. This research aimed to
      evaluate the efficacy and safety of the GELOXD or P-GEMOXD regimens in patients
      with ENKTCL. METHODS: Newly diagnosed ENKTCL patients treated with either the
      GELOXD or the P-GEMOXD regimen were identified from three cancer centers between
      January 2010 and December 2016. Kaplan-Meier and Cox regression analyses were
      used to calculate overall survival (OS) and progression-free survival (PFS) and
      to investigate prognostic factors. RESULTS: One hundred and eighty-four cases
      were identified from three cancer centers. After 1-5 treatment cycles of GELOXD
      or P-GEMOXD chemotherapy, 155 (84%) patients showed a complete response (CR). The
      3-year OS (73.0% vs 38.2%, P = .001) and PFS (72.8% vs 32.4%, P = .000) rates
      were significantly higher in early-stage patients compared with advanced-stage
      patients. A multivariate analysis revealed that patient CR status was a
      significant independent factor in disease prognosis. Grade 3/4 leukopenia
      occurred in 43 (23.4%) patients. Major non-hematological toxicities included
      nausea (n = 117, 63.6%) and vomiting (n = 66, 35.9%). CONCLUSIONS: The GELOXD and
      P-GEMOXD chemotherapy regimens are well tolerated and provide favorable survival
      outcomes in patients with ENKTCL.

PMID- 29194799
TI  - Hyperstage Graphite: Electrochemical Synthesis and Spontaneous Reactive
      Exfoliation.
AB  - Covalent modification of the pi-electron basal planes of graphene enables the
      formation of new materials with enhanced functionality. An electrochemical method
      is reported for the formation of what is referred to as a Hyperstage-1 graphite
      intercalation compound (GIC), which has a very large interlayer spacing d001 >
      15.3 A and contains disordered interstitial molecules/ions. This material is
      highly activated and undergoes spontaneous exfoliation when reacted with
      diazonium ions to produce soluble graphenes with high functionalization densities
      of one pendant aromatic ring for every 12 graphene carbons. Critical to achieving
      high functionalization density is the Hyperstage-1 GIC state, a weakening of the
      van der Waals coupling between adjacent graphene layers, and the ability of
      reactants to diffuse into the disordered intercalate phase between the layers.
      Graphene functionalization with 3,5-dinitrophenyl groups provides for exceptional
      dispersibility (0.24 mg mL-1 ) in N,N-dimethylformamide and for conjugation with
      amines.

PMID- 29194800
TI  - Expression of IFNAR1 and IFNAR2 in cattle placenta during early pregnancy.
AB  - Interferon-tau (IFNT), a type I interferon, is an antiluteolytic factor secreted
      by trophoderm during pregnancy. IFNT transmitted signals or stimulated the
      expression of some factors to build maternal recognition and keep pregnancy by
      binding its receptors, IFNT receptor 1(IFNAR1) and IFNT receptor 2 (IFNAR2). Up
      to now, the expression model and roles of IFNAR1 and IFNAR2 in placenta have not
      been investigated in cattle. In this study, the localization and expression of
      IFNAR1 and IFNAR2 in the cattle placenta at days 18-50 of pregnancy were detected
      by histological examination, immunofluorescence staining and real-time qPCR. The
      results showed that IFNAR1 mainly distributed in chorioallantoic membrane,
      endometrial epithelium, cotyledon and caruncle during the early pregnancy of
      cattle with change in time- and position-dependent. IFNAR1 and IFNAR2 mRNA
      expression were mainly detected in chorioallantoic membrane and cotyledon, and
      markedly increased along with pregnancy process. Moreover, the mRNA expression
      level of IFNAR1 in chorioallantoic membrane and cotyledon was higher than that of
      IFNAR2. IFNAR mRNA was also expressed in caruncle tissues, which experienced a
      tendency of decrease from days 21 to 36, followed by increase after days 36.
      These results provide morphological basis and quantitative data for investigating
      the roles of IFNAR1 and IFNAR2 on development of cattle placenta and pregnancy
      maintenance.

PMID- 29194801
TI  - Measurement of HE4 and CA125 and establishment of reference intervals for the
      ROMA index in the sera of pregnant women.
AB  - INTRODUCTION: Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are
      biomarkers for ovarian cancer. Their specificity and sensitivity are often
      limited during pregnancy as a result of great fluctuations. The risk of ovarian
      malignancy algorithm (ROMA) score, which combines CA125, HE4, and menopausal
      status, may improve diagnostic performance. There are no reports regarding the
      ROMA index in pregnant women. Therefore, the aim of our study was to establish
      appropriate reference intervals (RIs) for the ROMA index in pregnant Chinese
      women and compare them with those of CA125 and HE4 during pregnancy. METHODS:
      Serum concentrations of CA125 and HE4 were simultaneously measured in healthy
      pregnant women via electrochemiluminescence immunoassay (ECLIA). The ROMA index
      was calculated using premenopausal algorithms. RESULTS: The RIs for the ROMA
      index calculated by premenopausal algorithms were substantially closer to the
      normal range in the first 2 trimesters. For pregnant women, the great
      misclassifications identified in CA125 may be reversed by the use of ROMA index.
      CONCLUSIONS: We established the RIs for HE4 and CA125, as well as the ROMA index,
      in pregnant women at different gestational periods. The ROMA index is suggested
      to be a more promising tumor marker for pregnant women diagnosed with malignance.

PMID- 29194802
TI  - Acne across Europe: an online survey on perceptions and management of acne.
AB  - BACKGROUND: Acne is common among young people. OBJECTIVE: To describe the burden,
      management and sources of advice of acne in a representative sample of young
      people in Europe. METHODS: This cross-sectional survey was conducted in a
      representative sample of individuals aged 15-24 years from Belgium, Czech and
      Slovak Republics, France, Italy, Poland and Spain (n = 3099). RESULTS: Most
      individuals considered their acne (all severity stages) to be no/minor problem,
      although 29.7% considered it a major problem/burden. Over-the-counter (OTC)
      topical treatments were used more frequently than prescribed treatments. Acne was
      diagnosed by physicians in 47.6% of cases; other health professionals (nurses,
      pharmacists) or patients accounted for the remainder of diagnoses. Physicians
      were the source of acne information in just over one-quarter of cases (27.0%).
      The vast majority of advice was from friends/family and the Internet. CONCLUSION:
      Almost one-third of young people consider acne to be a major problem/burden.
      Fewer than half of acne diagnoses are made by a physician, and acne is often self
      managed using OTC treatments.

PMID- 29194803
TI  - A Li-Air Battery with Ultralong Cycle Life in Ambient Air.
AB  - The Li-air battery represents a promising power candidate for future electronics
      due to its extremely high energy density. However, the use of Li-air batteries is
      largely limited by their poor cyclability in ambient air. Herein, Li-air
      batteries with ultralong 610 cycles in ambient air are created by combination of
      low-density polyethylene film that prevents water erosion and gel electrolyte
      that contains a redox mediator of LiI. The low-density polyethylene film can
      restrain the side reactions of the discharge product of Li2 O2 to Li2 CO3 in
      ambient air, while the LiI can facilitate the electrochemical decomposition of
      Li2 O2 during charging, which improves the reversibility of the Li-air battery.
      All the components of the Li-air battery are flexible, which is particularly
      desirable for portable and wearable electronic devices.

PMID- 29194804
TI  - The use of ultrasonography in the reproductive evaluation of boars.
AB  - The objective was to study the use of ultrasound as a complementary test in the
      breeding soundness evaluation in male pigs and study the pattern of echogenicity
      of the testicular parenchyma in boars of different racial groups. Twenty-six
      adult boars from four different racial groups were used, 10 from the Piau breed
      (group 1), four from the commercial and finishing group (group 2), six Pietrain
      breed (group 3) and six from the Duroc breed (group 4). All animals were
      evaluated for breeding soundness evaluation and the ultrasound examination of the
      testicles. The groups of animals that were evaluated showed no difference in the
      main semen parameters that were evaluated, except for the sperm volume,
      concentration of the ejaculated sperm and the supravital staining; the lowest
      figures were for the animals from the Piau breed (group 1). In relation to the
      testicular biometrics, Duroc animals (group 4) had a greater scrotal width
      compared to the other groups. But when we assessed the intensity of pixels of the
      testicles, there was a difference between groups. The groups 2 (finishing
      animals), 3 (Pietrain) and 4 had no difference between themselves. Group 3 had
      greater pixel intensity in relation to group 1. Of the 26 animals studied, five
      showed an abnormality during ultrasound evaluation, like hydrocele, hyperechoic
      mass in the testicular parenchyma, cyst in the head of the epididymis and the
      presence of fluid in the head and tail of the epididymis. The various animal
      groups studied did not differ in the principal reproductive parameters evaluated,
      showing that despite the great variability of reproductive traits between breeds
      and within the same breed, the breeding soundness evaluation, the more complete
      it is, is essential for the selection of breeders and the ultrasonography of the
      reproductive system becomes an important addition in this examination.

PMID- 29194805
TI  - Efficacy of ustekinumab in palmoplantar pustulosis.

PMID- 29194806
TI  - A Direct Prebiotic Synthesis of Nicotinamide Nucleotide.
AB  - The "RNA World" hypothesis proposes an early episode of the natural history of
      Earth, where RNA was used as the only genetically encoded molecule to catalyze
      steps in its metabolism. This, according to the hypothesis, included RNA
      catalysts that used RNA cofactors. However, the RNA World hypothesis places
      special demands on prebiotic chemistry, which must now deliver not only four
      ribonucleosides, but also must deliver the "functional" portion of these RNA
      cofactors. While some (e.g., methionine) present no particular challenges,
      nicotinamide ribose is special. Essential to its role in biological oxidations
      and reductions, its glycosidic bond that holds a positively charged heterocycle
      is especially unstable with respect to cleavage. Nevertheless, we are able to
      report here a prebiotic synthesis of phosphorylated nicotinamide ribose under
      conditions that also conveniently lead to the adenosine phosphate components of
      this and other RNA cofactors.

PMID- 29194808
TI  - The changing landscape of surgery for Parkinson's Disease.
AB  - Neurosurgical interventions have been used to treat PD for over a century. We
      examined the changing landscape of surgery for PD to appraise the value of
      various procedures in the context of advances in our understanding and
      technology. We assessed the number of articles published on neurosurgical
      procedures for PD over time as an albeit imprecise surrogate for their usage
      level. We identified over 8,000 publications associated with PD surgery. Over
      half the publications were on DBS. The field of DBS for PD showed a rapid rise in
      articles, but is now in a steady state. Thalamotomy and, to a lesser extent,
      pallidotomy follow a biphasic publication distribution with peaks approximately
      30 years apart. Articles on gene therapy and transplantation experienced initial
      rapid rises and significant recent declines. Procedures using novel technologies,
      including gamma knife and focused ultrasound, are emerging, but are yet to have
      significant impact as measured by publication numbers. Pallidotomy and
      thalamotomy are prominent examples of procedures that were popular, declined, and
      re-emerged and redeclined. Transplantation and gene therapy have never broken
      into clinical practice. DBS overtook all procedures as the dominant surgical
      intervention and drove widespread use of surgery for PD. Notwithstanding, the
      number of DBS articles appears to have plateaued. As advances continue, emerging
      treatments may compete with DBS in the future. (c) 2017 International Parkinson
      and Movement Disorder Society.

PMID- 29194807
TI  - Prevalence of the AMHR2 mutation in Miniature Schnauzers and genetic
      investigation of a Belgian Malinois with persistent Mullerian duct syndrome.
AB  - Persistent Mullerian duct syndrome (PMDS) is a sex-limited disorder in which
      males develop portions of the female reproductive tract. Important consequences
      of PMDS are cryptorchidism and its sequelae of infertility and increased risk of
      testicular cancer. Anti-Mullerian hormone (AMH) and its receptor (AMHR2) induce
      the regression of the Mullerian ducts in male embryos. In Miniature Schnauzer
      dogs, the genetic basis has been identified as an autosomal recessive nonsense
      mutation in AMHR2, but the allele frequency of the mutation is unknown. Thus, the
      primary objective of this study was to estimate the prevalence of the AMHR2
      mutation in North American Miniature Schnauzers, in order to ascertain the value
      of genetic testing in this breed. An additional objective was to determine
      whether mutations in AMH or AMHR2 were responsible for PMDS in a Belgian
      Malinois; this would aid development of a genetic test for the Belgian Malinois
      breed. Genomic DNA from 216 Miniature Schnauzers (including one known PMDS case)
      was genotyped for the AMHR2 mutation, and DNA from a single PMDS-affected Belgian
      Malinois was sequenced for all coding exons of AMH and AMHR2. The Miniature
      Schnauzer cohort had an AMHR2 mutation allele frequency of 0.16 and a carrier
      genotypic frequency of 0.27. The genetic basis for PMDS in the Belgian Malinois
      was not determined, as no coding or splicing mutations were identified in either
      AMH or AMHR2. These findings support a benefit to AMHR2 mutation testing
      Miniature Schnauzers used for breeding or with cryptorchidism.

PMID- 29194809
TI  - Methylsemicarbazide as a Ligand in Late 3d Transition Metal Complexes.
AB  - Most ignition and initiation systems nowadays still contain poisonous chemicals
      such as lead styphnate and lead azide but also chromates and other compounds of
      high concern. Therefore, methylsemicarbazide (1, MSC), which can be prepared in a
      one-step reaction and in an extraordinary high yield of 95 %, has been evaluated
      as ligand in energetic coordination compounds. For the first time 25 new
      transition metal complexes (Mn2+ , Ni2+ , Co2+ , Cu2+ , and Zn2+ ) using
      methylsemicarbazide (1) as the ligand were prepared and comprehensively analyzed
      by, for example, XRD, IR, EA, UV/Vis and DSC/DTA/TGA. Many show a strong
      energetic character, which can be tuned by using different anions such as Cl- ,
      SO42- , NO3- , ClO4- , picrate or styphnate. Selected compounds were additionally
      evaluated as lead-free primary explosives in initiation tests (nitropenta filled
      detonators) and in laser ignition systems. Especially compound 7 showed very
      promising results during these tests and could be a potential candidate for
      future applications.

PMID- 29194810
TI  - Highly Multiplexed Single-Cell Protein Analysis.
AB  - Single-cell proteomic analysis is crucial to advance our understanding of normal
      physiology and disease pathogenesis. The comprehensive protein profiling in
      individual cells of a heterogeneous sample can provide new insights into many
      important biological issues, such as the regulation of inter- and intracellular
      signaling pathways or the varied cellular compositions of normal and diseased
      tissues. With highly multiplexed molecular imaging of many different protein
      biomarkers in patient biopsies, diseases can be accurately diagnosed to guide the
      selection of the ideal treatment. In this Minireview, we will describe the recent
      technological advances of single-cell proteomic assays, discuss their advantages
      and limitations, highlight their applications in biology and precision medicine,
      and present the current challenges and potential solutions.

PMID- 29194811
TI  - Organic-Inorganic Hybrid Materials: Multi-Functional Solids for Multi-Step
      Reaction Processes.
AB  - The design of new hybrid materials with tailored properties at the nano-, meso-,
      and macro-scale, with the use of structural functional nanobuilding units, is
      carried out to obtain specific multi-functional materials. Organization into
      controlled 1D, 2D, and 3D architectures with selected functionalities is key for
      developing advanced catalysts, but this is hardly accomplished using conventional
      synthesis procedures. The use of pre-formed nanostructures, derived either from
      known materials or made with specific innovative synthetic methodologies, has
      enormous potential in the generation of multi-site catalytic materials for one
      pot processes. The present concept article introduces a new archetype wherein
      self-assembled nanostructured builder units are the base for the design of
      multifunctional catalysts, which combine catalytic efficiency with fast reactant
      and product diffusion. The article addresses a new generation of versatile hybrid
      organic-inorganic multi-site catalytic materials for their use in the production
      of (chiral) high-added-value products within the scope of chemicals and fine
      chemicals production. The use of those multi-reactive solids for more
      nanotechnological applications, such as sensors, due to the inclusion of electron
      donor-acceptor structural arrays is also considered, together with the adsorption
      desorption capacities due to the combination of hydrophobic and hydrophilic sub
      domains. The innovative structured hybrid materials for multipurpose processes
      here considered, can allow the development of multi-stage one-pot reactions with
      industrial applications, using the materials as one nanoreactor systems, favoring
      more sustainable production pathways with economic, environmental and energetic
      advantages.

PMID- 29194812
TI  - Versatile cell surface structures of archaea.
AB  - Archaea are ubiquitously present in nature and colonize environments with broadly
      varying growth conditions. Several surface appendages support their colonization
      of new habitats. A hallmark of archaea seems to be the high abundance of type IV
      pili (T4P). However, some unique non T4 filaments are present in a number of
      archaeal species. Archaeal surface structures can mediate different processes
      such as cellular surface adhesion, DNA exchange, motility and biofilm formation
      and represent an initial attachment site for infecting viruses. In addition to
      the functionally characterized archaeal T4P, archaeal genomes encode a large
      number of T4P components that might form yet undiscovered surface structures with
      novel functions. In this review, we summarize recent advancement in structural
      and functional characterizations of known archaeal surface structures and
      highlight the diverse processes in which they play a role.

PMID- 29194813
TI  - Green Photo-Organocatalytic C-H Activation of Aldehydes: Selective Hydroacylation
      of Electron-Deficient Alkenes.
AB  - Selective C-H activation is an area of growing importance. Metal-free C-H
      activation of branched aldehydes mediating the hydroacylation of electron
      deficient alkenes is an attractive transformation, but is limited by selectivity
      issues, especially in the case of alpha,alpha-disubstituted aldehydes. Herein, we
      report a green, cheap, versatile, and easily reproducible selective
      hydroacylation of alkenes utilizing phenylglyoxylic acid as the photocatalyst and
      common household bulbs for irradiation, leading to products in excellent yields
      and selectivities. The reaction mechanism was also studied to account for the
      high selectivity.

PMID- 29194815
TI  - The new Pan-American Neuroendocrine Society.

PMID- 29194814
TI  - How sildenafil (Viagra(r) ) may cause melanoma: a histopathologic study providing
      a potential physiological/etiopathological mechanism.

PMID- 29194816
TI  - Programming Recognition Arrays through Double Chalcogen-Bonding Interactions.
AB  - In this work, we have programmed and synthesized a recognition motif constructed
      around a chalcogenazolo-pyridine scaffold (CGP) that, through the formation of
      frontal double chalcogen-bonding interactions, associates into dimeric EX-type
      complexes. The reliability of the double chalcogen-bonding interaction has been
      shown at the solid-state by X-ray analysis, depicting the strongest recognition
      persistence for a Te-congener. The high recognition fidelity, chemical and
      thermal stability and easy derivatization at the 2-position makes CGP a
      convenient motif for constructing supramolecular architectures through programmed
      chalcogen-bonding interactions.

PMID- 29194817
TI  - Porphyrin-Based Air-Stable Helical Radicals.
AB  - Stable helical radicals are promising multi-functional molecules in light of
      intriguing magnetic and chiroptical properties. Attempts were made to extend
      diphenylmethyl-fused NiII porphyrin radical to helical system as the first air
      stable organic neutral helical radicals. Intramolecular Pd-catalyzed twofold C-H
      arylation of methyl- or methoxy-introduced meso-diphenylmethyl NiII porphyrins
      gave a mixture of the target and rearranged radicals. Oxidative fusion reaction
      of meso-(bis(1-naphthyl)methyl) NiII porphyrins provided doubly fused NiII
      porphyrin radicals. One of the helical radicals was separated into enantiomers
      that showed mirror-image circular dichroism (CD) spectra up to 1300 nm. The
      helical dinaphthylmethyl-fused NiII porphyrin radical displayed solid-state
      magnetic property mostly arising from monomeric radicals, different from the
      parent diphenylmethyl-fused NiII porphyrin radical that showed antiferromagnetic
      coupling due to pi-stacked pairing.

PMID- 29194818
TI  - Rapid nongenomic modulation by neurosteroids of dendritic spines in the
      hippocampus: Androgen, oestrogen and corticosteroid.
AB  - Memories are stored in synapses that consist of axon terminals and dendritic
      spines. Dendritic spines are postsynaptic structures of synapses and are
      essential for synaptic plasticity and cognition. Therefore, extensive
      investigations concerning the functions and structures of spines have been
      performed. Sex steroids and stress steroids have been shown to modulate
      hippocampal synapses. Although the rapid modulatory action of sex steroids on
      synapses has been studied in hippocampal neurones over several decades, the
      essential molecular mechanisms have not been fully understood. Here, a
      description of kinase-dependent signalling mechanisms is provided that can
      explain the rapid nongenomic modulation of dendritic spinogenesis in rat and
      mouse hippocampal slices by the application of sex steroids, including
      dihydrotestosterone, testosterone, oestradiol and progesterone. We also indicate
      the role of synaptic (classic) sex steroid receptors that trigger these rapid
      synaptic modulations. Moreover, we describe rapid nongenomic spine modulation by
      applying corticosterone, which is an acute stress model of the hippocampus. The
      explanations for the results obtained are mainly based on the optical imaging of
      dendritic spines. Comparisons are also performed with results obtained from other
      types of imaging, including electron microscopic imaging. Relationships between
      spine modulation and modulation of cognition are discussed. We recognise that
      most of rapid effects of exogenously applied oestrogen and androgen were observed
      in steroid-depleted conditions, including acute slices of the hippocampus,
      castrated male animals and ovariectomised female animals. Therefore, the
      previously observed effects can be considered as a type of recovery event, which
      may be essentially similar to hormone replacement therapy under hormone-decreased
      conditions. On the other hand, in gonadally intact young animals with high levels
      of endogenous sex hormones, further supplementation of sex hormones might not be
      effective, whereas the infusion of blockers for steroid receptors or kinases may
      be effective, with respect to suppressing sex hormone functions, thus providing
      useful information regarding molecular mechanisms.

PMID- 29194819
TI  - Optical Properties and Sequence Information of Tin-Centered Conjugated
      Microporous Polymers.
AB  - We synthesized conjugated microporous polymers (CMPs) based on tetrakis(4
      ethynylphenyl)stannane and diiodobenzene as tectons, using Sonogashira couplings
      under different conditions. Through variation of the reaction conditions
      (catalysts, bases and solvents), appearance, surface area and emission properties
      of the formed CMPs were significantly altered. Wet-chemical, acid-mediated
      digestion and analysis of the resulting struts of these otherwise insoluble
      networks give insight into the molecular setup.

PMID- 29194820
TI  - Evidence for Iron-Catalyzed alpha-Phosphinidene Elimination with Phenylphosphine.
AB  - The ubiquitous half-sandwich iron complex [CpFe(CO)2 Me] (Cp=eta5 -C5 H5 )
      appears to be a catalyst for alpha-phosphinidene elimination from primary
      phosphines. Dehydrocoupling reactions provided initial insight into this unusual
      reaction mechanism, and trapping reactions with organic substrates gave products
      consistent with an alpha elimination mechanism, including a rare example of a
      three-component reaction. The substrate scope of this reaction is consistent with
      generation of a triplet phosphinidene. In all, this study presents catalytic
      phosphinidene transfer to unsaturated organic substrates.

PMID- 29194822
TI  - De Novo Synthesis of Benzannelated Heterocycles.
AB  - Benzannelated heterocycles such as indoles and indazoles are prominent structural
      motifs found in natural products, pharmaceuticals and agrochemicals. For their
      synthesis, chemists traditionally either functionalize commercially available
      heterocycles or resort to transformations that make use of benzene-derived
      building blocks. Here, we report a powerful cascade reaction that enables the de
      novo construction of variously substituted indoles, indazoles, benzofurans and
      benzothiophenes from readily available bicyclo[3.1.0]hexan-2-ones. The
      transformation can be conducted under mild, non-anhydrous conditions. For the
      synthesis of indoles, mechanistic studies revealed that the electrocyclic ring
      opening of the bicyclic ring-system and aromatization precedes the 3,3
      sigmatropic rearrangement.

PMID- 29194823
TI  - A Macroporous Metal-Organic Framework with Enhanced Hydrophobicity for Efficient
      Oil Adsorption.
AB  - The applications of three-dimensional superstructures that consist of metal
      organic framework (MOF) crystals are promising, but limited by spatial control
      over the crystallization process. Here a hydrophobic hierarchical metal-organic
      framework (HZIF-8) containing unusual micro-, meso-, and macropores was designed
      and synthesized by a template strategy, in which the polystyrene (PS) not only
      acted as the template to construct the macropores, but also modified the
      hydrophilic crystal surface of ZIF-8. When used as adsorbent for liquid oil/water
      separation, HZIF-8 demonstrated significantly enhanced oil adsorption performance
      while maintaining very low water uptake.

PMID- 29194824
TI  - Preparation of a Si/SiO2 -Ordered-Mesoporous-Carbon Nanocomposite as an Anode for
      High-Performance Lithium-Ion and Sodium-Ion Batteries.
AB  - In this work, an Si/SiO2 -ordered-mesoporous carbon (Si/SiO2 -OMC) nanocomposite
      was initially fabricated through a magnesiothermic reduction strategy by using a
      two-dimensional bicontinuous mesochannel of SiO2 -OMC as a precursor, combined
      with an NaOH etching process, in which crystal Si/amorphous SiO2 nanoparticles
      were encapsulated into the OMC matrix. Not only can such unique porous crystal
      Si/amorphous SiO2 nanoparticles uniformly dispersed in the OMC matrix mitigate
      the volume change of active materials during the cycling process, but they can
      also improve electrical conductivity of Si/SiO2 and facilitate the Li+ /Na+
      diffusion. When applied as an anode for lithium-ion batteries (LIBs), the Si/SiO2
      -OMC composite displayed superior reversible capacity (958 mA h g-1 at 0.2 A g-1
      after 100 cycles) and good cycling life (retaining a capacity of 459 mA h g-1 at
      2 A g-1 after 1000 cycles). For sodium-ion batteries (SIBs), the composite
      maintained a high capacity of 423 mA h g-1 after 100 cycles at 0.05 A g-1 and an
      extremely stable reversible capacity of 190 mA h g-1 was retained even after 500
      cycles at 1 A g-1 . This performance is one of the best long-term cycling
      properties of Si-based SIB anode materials. The Si/SiO2 -OMC composites exhibited
      great potential as an alternative material for both lithium- and sodium-ion
      battery anodes.

PMID- 29194825
TI  - Drastic Effect of the Peptide Sequence on the Copper-Binding Properties of
      Tripeptides and the Electrochemical Behaviour of Their Copper(II) Complexes.
AB  - The binding and electrochemical properties of the complexes CuII -HAH, CuII -HWH,
      CuII -Ac-HWH, CuII -HHW, and CuII -WHH have been studied by using NMR and UV/Vis
      spectroscopies, CV, and density functional calculations. The results obtained
      highlight the importance of the peptidic sequence on the coordination properties
      and, consequently, on the redox properties of their CuII complexes. For CuII -HAH
      and CuII -HWH, no cathodic processes are observed up to -1.2 V; that is, the
      complexes exhibit very high stability towards copper reduction. This behaviour is
      associated with the formation of very stable square-planar (5,5,6)-membered
      chelate rings (ATCUN motif), which enclose two deprotonated amides. In contrast,
      for non-ATCUN CuII -Ac-HWH, CuII -HHW complexes, simulations seem to indicate
      that only one deprotonated amide is enclosed in the coordination sphere. In these
      cases, the main electrochemical feature is a reductive irreversible one electron
      transfer process from CuII to CuI , accompanied with structural changes of the
      metal coordination sphere and reprotonation of the amide. Finally, for CuII -WHH,
      two major species have been detected: one at low pH (<5), with no deprotonated
      amides, and another one at high pH (>10) with an ATCUN motif, both species
      coexisting at intermediate pH. The present study shows that the use of CV, using
      glassy carbon as a working electrode, is an ideal and rapid tool for the
      determination of the redox properties of CuII metallopeptides.

PMID- 29194826
TI  - Disentangling sex allocation in a viviparous reptile with temperature-dependent
      sex determination: a multifactorial approach.
AB  - Females are predicted to alter sex allocation when ecological, physiological and
      behavioural variables have different consequences on the fitness of male and
      female offspring. Traditionally, tests of sex allocation have examined single
      causative factors, often ignoring possible interactions between multiple factors.
      Here, we used a multifactorial approach to examine sex allocation in the
      viviparous skink, Niveoscincus ocellatus. We integrated a 16-year observational
      field study with a manipulative laboratory experiment to explore whether the
      effects of the maternal thermal environment interact with the resources available
      to females for reproduction to affect sex allocation decisions. We found strong
      effects of temperature on sex allocation in the field, with females born in warm
      conditions and males in cold conditions; however, this was not replicated in the
      laboratory. In contrast, we found no effect of female resource availability on
      sex allocation, either independently, or in interaction with temperature. These
      results corresponded with an overall lack of an effect of resource availability
      on any of the life history traits that we predicted would mediate the benefits of
      differential sex allocation in this system, suggesting that selection for sex
      allocation in response to resource availability may be relatively weak. Combined,
      these results suggest that temperature may be the predominant factor driving sex
      allocation in this system.

PMID- 29194827
TI  - Downregulation of lncRNA CASC2 facilitates osteosarcoma growth and invasion
      through miR-181a.
AB  - OBJECTIVES: Long non-coding RNA cancer susceptibility candidate 2 (CASC2) is a
      novel lncRNA and has been indicated as playing tumour suppressor gene in several
      tumours. However, the role of CASC2 in osteosarcoma is still uncovered. MATERIALS
      AND METHODS: The CASC2 and miR-181a expressions were measured via qRT-PCR. CCK-8
      assay and colony formation assay were performed to determine the cell growth, and
      transwell assay was performed to assess the cell invasion. RESULTS: We showed
      that CASC2 expression was downregulated in osteosarcoma samples and cell lines.
      Moreover, we showed that downregulated expression of CASC2 was correlated with
      advanced TNM stage. Furthermore, overexpression of CASC2 inhibited osteosarcoma
      cell proliferation, colony formation, and invasion. In addition, we indicated
      that ectopic expression of CASC2 suppressed miR-181a expression and enhanced the
      expression of Ras association domain family member 6 (RASSF6), PTEN and ATM in
      osteosarcoma cell, which were the direct target gene of miR-181a. Moreover, we
      indicated that RASSF6 expression was downregulated in osteosarcoma samples and
      cell lines and downregulated expression of RASSF6 was correlated with advanced
      TNM stage. We found that the expression of RASSF6 was positively correlated with
      the expression of CASC2 in osteosarcoma tissues. Ectopic expression of CASC2
      suppressed the osteosarcoma cell proliferation, colony formation and invasion
      through regulating RASSF6 expression. CONCLUSIONS: Our data illuminated that
      CASC2 acted as a tumour suppressor in osteosarcoma progression.

PMID- 29194828
TI  - Caught between a rock and a hard place: An intrinsic single case study of nurse
      researchers' experiences of the presence of a nursing research culture in
      clinical practice.
AB  - AIMS AND OBJECTIVES: To explore how nurse researchers in clinical positions
      experience the presence of a nursing research culture in clinical practice.
      BACKGROUND: Higher demands in the hospitals for increasing the quality of patient
      care engender a higher demand for the skills of health professionals and evidence
      based practice. However, the utilisation of nursing research in clinical practice
      is still limited. DESIGN: Intrinsic single case study design underlined by a
      constructivist perspective. METHODS: Data were produced through a focus group
      interview with seven nurse researchers employed in clinical practice in two
      university hospitals in Zealand, Denmark, to capture the intrinsic aspects of the
      concept of nursing research culture in the context of clinical practice. A
      thematic analysis was conducted based on Braun and Clarke's theoretical
      guideline. RESULTS: "Caught between a rock and a hard place" was constructed as
      the main theme describing how nurse researchers in clinical positions experience
      the presence of a nursing research culture in clinical practice. The main theme
      was supported by three subthemes: Minimal academic tradition affects nursing
      research; Minimal recognition from physicians affects nursing research; and
      Moving towards a research culture. CONCLUSIONS: The nurse researchers in this
      study did not experience the presence of a nursing research culture in clinical
      practice, however; they called for more attention on removing barriers against
      research utilisation, promotion of applied research and interdisciplinary
      research collaboration, and passionate management support. RELEVANCE TO CLINICAL
      PRACTICE: The results of this case study show the pressure which nurse
      researchers employed in clinical practice are exposed to, and give examples on
      how to accommodate the further development of a nursing research culture in
      clinical practice.

PMID- 29194829
TI  - On the helical arrangements of protein molecules.
AB  - Helical structures are prevalent in biology. In the PDB, there are many examples
      where protein molecules are helically arranged, not only according to strict
      crystallographic screw axes but also according to approximate noncrystallographic
      screws. The preponderance of such screws is rather striking as helical
      arrangements in crystals must preserve an integer number of subunits per turn,
      while intuition and simple packing arguments would seem to favor fractional
      helices. The article provides insights into such questions, based on
      stereochemistry, trigonometry, and topology, and illustrates the findings with
      concrete PDB structures. Updated statistics of Sohncke space groups in the PDB
      are also presented.

PMID- 29194830
TI  - Effect of Intraoral Mechanical Cleaning Techniques on Bond Strength of Cast
      Crowns to Metal Cores.
AB  - PURPOSE: To evaluate the effect of cleaning of metal cores from provisional
      cement, using an intraoral airborne-particle abrasion method, on the bond
      strength of permanent resin cement with cast crowns to cores. MATERIALS AND
      METHODS: Thirty stainless steel models of a standard complete crown tooth
      preparation were fabricated. Thirty Type III gold crowns were fabricated. Each
      cast crown corresponded to one stainless steel crown preparation model. All
      crowns were cemented with noneugenol zinc oxide cement and stored for 7 days at
      37 degrees C. All crowns were debonded, and the cement was cleaned with airborne
      particle abrasion using 50 MUm aluminum oxide at 4.1 bar (0.41 MPa) followed by
      ultrasonic cleaning. Based on the mechanical cleaning technique of the remaining
      provisional cement on surfaces of cast cores, specimens were equally divided into
      3 groups: hand cleaning (HC) with a dental excavator, hand cleaning followed by
      polishing using a brush and pumice (BP), and hand cleaning followed by intraoral
      airborne-particle abrasion (APA). All crowns were then cemented to their
      corresponding cores using universal resin cement. All crowns were stored for 7
      days at 37 degrees C. An Instron universal testing machine was used to record the
      bond strength of crowns. RESULTS: Airborne-particle abrasion method for intraoral
      mechanical cleaning revealed a statistically significantly higher bond strength
      compared to the other two methods. CONCLUSIONS: When comparing the three methods
      of provisional cement cleaning from metal cores, airborne-particle abrasion
      resulted in the highest bond strength for cast crowns.

PMID- 29194831
TI  - Analysis of arrhythmic events is useful to detect lead failure earlier in
      patients followed by remote monitoring.
AB  - BACKGROUND: Remote monitoring (RM) has been advocated as the new standard of care
      for patients with cardiovascular implantable electronic devices (CIEDs). RM has
      allowed the early detection of adverse clinical events, such as arrhythmia, lead
      failure, and battery depletion. However, lead failure was often identified only
      by arrhythmic events, but not impedance abnormalities. OBJECTIVE: To compare the
      usefulness of arrhythmic events with conventional impedance abnormalities for
      identifying lead failure in CIED patients followed by RM. METHODS: CIED patients
      in 12 hospitals have been followed by the RM center in Okayama University
      Hospital. All transmitted data have been analyzed and summarized. RESULTS: From
      April 2009 to March 2016, 1,873 patients have been followed by the RM center.
      During the mean follow-up period of 775 days, 42 lead failure events (atrial lead
      22, right ventricular pacemaker lead 5, implantable cardioverter defibrillator
      [ICD] lead 15) were detected. The proportion of lead failures detected only by
      arrhythmic events, which were not detected by conventional impedance
      abnormalities, was significantly higher than that detected by impedance
      abnormalities (arrhythmic event 76.2%, 95% CI: 60.5-87.9%; impedance
      abnormalities 23.8%, 95% CI: 12.1-39.5%). Twenty-seven events (64.7%) were
      detected without any alert. Of 15 patients with ICD lead failure, none has
      experienced inappropriate therapy. CONCLUSIONS: RM can detect lead failure
      earlier, before clinical adverse events. However, CIEDs often diagnose lead
      failure as just arrhythmic events without any warning. Thus, to detect lead
      failure earlier, careful human analysis of arrhythmic events is useful.

PMID- 29194832
TI  - The pathogenesis of paraesophageal empyema in dogs and constancy of radiographic
      and computed tomography signs are linked to involvement of the mediastinal serous
      cavity.
AB  - The mediastinal serous cavity is a normal anatomic space in the caudal
      mediastinum. Aims of this anatomic and case series study were to describe the
      signs of pathologic expansion of the mediastinal serous cavity observed during
      computed tomography (CT), review the underlying anatomy, perform a literature
      review, and evaluate the medical records of several dogs with mediastinal serous
      cavity empyema (paraesophageal empyema). The mesothelial lined mediastinal serous
      cavity is a cranial extension of the omental bursa, separated from the peritoneal
      cavity by the diaphragm, in the dorsal part of the caudal mediastinum, to the
      right of the esophagus, between the heart base and diaphragm. In five adult,
      large-breed dogs with surgically and histologically confirmed paraesophageal
      empyema, macroscopic plant material was found at surgery in two dogs, adherence
      to adjacent lung was present in three different dogs, accessory lobectomy was
      performed in two dogs with subacute-chronic pyogranulomatous pneumonia, and one
      dog had concurrent pyothorax and mediastinitis, but none had esophageal
      abnormalities. This study expands our understanding of the pathogenesis and basis
      for the imaging appearance of paraesophageal empyema in dogs by clarifying the
      underlying anatomic structures that direct development of this condition. The
      term empyema accurately describes this condition because the purulent material
      accumulates within an existing body cavity. The study also provides initial
      evidence that the development of paraesophageal empyema might be due to local
      extension of lung disease, such as foreign body migration or pneumonia. Computed
      tomography was helpful for diagnosis, assessing size, and determining the spread
      of disease.

PMID- 29194833
TI  - Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic
      syndrome alter COQ8B function.
AB  - Mutations in COQ8B cause steroid-resistant nephrotic syndrome with variable
      neurological involvement. In yeast, COQ8 encodes a protein required for coenzyme
      Q (CoQ) biosynthesis, whose precise role is not clear. Humans harbor two paralog
      genes: COQ8A and COQ8B (previously termed ADCK3 and ADCK4). We have found that
      COQ8B is a mitochondrial matrix protein peripherally associated with the inner
      membrane. COQ8B can complement a DeltaCOQ8 yeast strain when its mitochondrial
      targeting sequence (MTS) is replaced by a yeast MTS. This model was employed to
      validate COQ8B mutations, and to establish genotype-phenotype correlations. All
      mutations affected respiratory growth, but there was no correlation between
      mutation type and the severity of the phenotype. In fact, contrary to the case of
      COQ2, where residual CoQ biosynthesis correlates with clinical severity, patients
      harboring hypomorphic COQ8B alleles did not display a different phenotype
      compared with those with null mutations. These data also suggest that the system
      is redundant, and that other proteins (probably COQ8A) may partially compensate
      for the absence of COQ8B. Finally, a COQ8B polymorphism, present in 50% of the
      European population (NM_024876.3:c.521A > G, p.His174Arg), affects stability of
      the protein and could represent a risk factor for secondary CoQ deficiencies or
      for other complex traits.

PMID- 29194834
TI  - Lipid-DNAs as Solubilizers of mTHPC.
AB  - Hydrophobic drug candidates require innovative formulation agents. We designed
      and synthesized lipid-DNA polymers containing varying numbers of hydrophobic
      alkyl chains. The hydrophobicity of these amphiphiles is easily tunable by
      introducing a defined number of alkyl chain-modified nucleotides during standard
      solid-phase synthesis of DNA using an automated DNA synthesizer. We observed that
      the resulting self-assembled micelles solubilize the poorly water-soluble drug,
      meta-tetra-hydroxyphenyl-chlorin (mTHPC) used in photodynamic therapy (PDT) with
      high loading concentrations and loading capacities. A cell viability study showed
      that mTHPC-loaded micelles exhibit good biocompatibility without irradiation, and
      high PDT efficacy upon irradiation. Lipid-DNAs provide a novel class of drug
      delivery vehicle, and hybridization of DNA offers a potentially facile route for
      further functionalization of the drug-delivery system with, for instance,
      targeting or imaging moieties.

PMID- 29194836
TI  - A Digital Approach to Retrofitting a Post and Core Restoration to an Existing
      Crown.
AB  - One problem that may arise in full-coverage restorations is clinical crown
      fracture. Fracture of an endodontically treated and crowned tooth in the esthetic
      zone may be embarrassing to both the patient and clinician. If a completely sound
      margin and at least 2 mm of coronal structure remain, a fractured tooth may
      possibly be retreated by a repair. Several methods have been introduced to
      reproduce the original contour of the tooth for retrofitting an existing crown.
      If an existing crown is used as a template, excessive core material may remain
      over the margin, as loading the proper amount of core material is difficult, and
      making vent holes on the existing crown is not feasible. This article presents a
      repair technique to reuse an existing crown with computer-aided design and
      computer-aided manufacturing (CAD/CAM) technology. By using a milled
      poly(methylmethacrylate) matrix, the mentioned limitations are eliminated, and
      the original contour of the tooth can be effectively restored with minimal
      intervention. As an existing crown is reused, the issues of additional time and
      cost for repreparation, reimpression, and new crown are eliminated.

PMID- 29194837
TI  - Substantial effects of empowerment case management on physical health of type 2
      diabetic patients.
AB  - AIMS AND OBJECTIVES: To evaluate the effects of empowerment case management on
      the physical health of patients with type 2 diabetes. BACKGROUND: Diabetes is a
      global health issue. Case management is often used on diabetes management at
      various levels. Empowerment has been used for chronic situation management, but
      its effects have not been widely studied in diabetic populations. DESIGN:
      Purposive sampling was used to recruit 125 participants with type 2 diabetes aged
      18 years or older from a regional teaching hospital in Taiwan. METHODS:
      Empowerment case management was applied for 42 participants, while the other 83
      received normal case management. Survey items included demographics, preprandial
      (AC) and postprandial (PC) blood sugar levels, glycated haemoglobin (HbA1C),
      systolic and diastolic blood pressure, total cholesterol, and the presence or
      absence of acute and chronic complications. Descriptive statistics and a
      generalised estimating equation were used to analyse the model's effects on the
      two groups. RESULTS: The PC blood sugar levels of patients receiving empowerment
      case management declined at 3 months (B = -34.26, p < .01), and this decrease was
      maintained at 6 months (B = -83.66, p < .001). As of 6 months after starting the
      intervention, patients receiving empowerment case management enjoyed better
      physical health. These patients' AC blood sugar levels (B = -50.16, p < .001),
      HbA1C (B = -0.98, p < .001), systolic blood pressure (B = -8.24, p < .001),
      diastolic blood pressure (B = -5.73, p < .01) and total cholesterol (B = -13.74,
      p < .05) all experienced a continuous drop and were controlled well, and no
      diabetes-related acute or chronic complications were observed either. Patients
      with type 2 diabetes who received empowerment case management managed their
      physical health better. Moreover, its greatest effect was that patients were able
      to form exercise groups and continue to maintain their health. CONCLUSIONS:
      Empowerment case management was shown to have a substantial effect on the
      physical health and self-care of patients with diabetes, thus making it a
      suitable intervention tool for managing diabetes cases. RELEVANCE TO CLINICAL
      PRACTICE: The study results showed that empowerment case management is suitable
      for managing diabetes cases. It has a substantial effect on the maintenance of
      physical health, occurrence of complications and effectiveness of self-care among
      patients with diabetes. For better care outcomes, empowerment case management
      should be integrated into the guidelines of diabetes management.

PMID- 29194835
TI  - Oxidative stress diseases unique to the perinatal period: A window into the
      developing innate immune response.
AB  - The innate immune system has evolved to play an integral role in the normally
      developing lung and brain. However, in response to oxidative stress, innate
      immunity, mediated by specific cellular and molecular programs and signaling,
      contributes to pathology in these same organ systems. Despite opposing drivers of
      oxidative stress, namely hyperoxia in neonatal lung injury and hypoxia/ischemia
      in neonatal brain injury, similar pathways-including toll-like receptors,
      NFkappaB and MAPK cascades-have been implicated in tissue damage. In this review,
      we consider recent insights into the innate immune response to oxidative stress
      in both neonatal and adult models to better understand hyperoxic lung injury and
      hypoxic-ischemic brain injury across development and aging. These insights
      support the development of targeted immunotherapeutic strategies to address the
      challenge of harnessing the innate immune system in oxidative stress diseases of
      the neonate.

PMID- 29194838
TI  - Reversible Modulation of Elasticity in Fluoroazobenzene-Containing Hydrogels
      Using Green and Blue Light.
AB  - Hydrogels are soft materials that have found multiple applications in biomedicine
      and represent a good platform for the introduction of molecular switches and
      synthetic machines into macromolecular networks. Tuning their mechanical
      properties reversibly with light is appealing for a variety of advanced
      applications and has been demonstrated in the past; however, their activation
      typically requires the use of UV light, which displays several drawbacks related
      to its damaging character and limited penetration in tissues and materials. This
      study circumvents this limitation by introducing all-visible ortho
      fluoroazobenzene switches into a hydrophilic network, which, as a result, can be
      activated with green or blue light. Photoisomerization of the photochromic
      moieties is accompanied by a reversible tuning of the elastic modulus. The
      translation of molecular isomerization within the network into macroscopic
      modulation of its mechanical properties is attributed to different aggregation
      tendencies of the E and Z isomers of the azobenzene derivatives.

PMID- 29194839
TI  - Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of
      ovarian endometriomas as candidate biomarkers of endometriosis.
AB  - PROBLEM: The diagnosis of endometriosis, a prevalent chronic disease with a
      strong inflammatory component, is usually delayed due to the lack of noninvasive
      diagnostic tests. Purinergic signaling, a key cell pathway, is altered in many
      inflammatory disorders. The aim of the present work was to evaluate the levels of
      adenosine deaminase (ADA), alkaline phosphatase (ALP), ecto-nucleotide
      pyrophosphatase/phosphodiesterase 1 (ENPP1), and ENPP3, elements of purinergic
      signaling, as biomarker candidates for endometriosis. METHOD OF STUDY: A case
      control comparative study was conducted to determine ADA, ALP, ENPP1 and ENPP3
      levels in echo-guided aspirated fluids of endometriomas (case group) and simple
      ovarian cysts (control group) using the ELISA technique. RESULTS: Adenosine
      deaminase, ALP, ENPP1, and ENPP3 were present and quantifiable in the contents of
      endometriomas and simple cysts. There were significant differences in ADA and
      ENPP1 levels in endometriomas in comparison with simple cysts (2787 U/L and 103.9
      ng/mL more in endometriomas, for ADA and ENPP1, respectively). Comparisons of ALP
      and ENPP3 levels between the two groups did not reveal significant differences.
      CONCLUSION: The ectoenzymes ADA and ENPP1 are biomarker candidates for
      endometriosis.

PMID- 29194841
TI  - Marginal and Internal Fit of CAD/CAM Crowns Fabricated Over Reverse Tapered
      Preparations.
AB  - PURPOSE: Intraoral digital scanning can accurately record single abutment tooth
      preparations despite their geometry, and the algorithms of the CAD software can
      be set to manage different abutment forms. The purpose of this in vitro study was
      to evaluate the marginal and internal fit of CAD/CAM zirconia crowns fabricated
      over conventional and reverse-tapered preparations. MATERIALS AND METHODS: Crown
      preparations with known total occlusal convergence (TOC) angles (-8 degrees , -4
      degrees , 0 degrees , 8 degrees , 12 degrees , 16 degrees , and 22 degrees ) were
      digitally created from a maxillary left central incisor and printed in acrylic
      resin. Next, casts were scanned with a TRIOS intraoral scanner, and crowns were
      designed with KaVo multiCAD software using default parameters (50 MUm cement
      space) on abutments with positive TOC angles, whereas reverse-tapered abutments
      (negative TOC angles) were digitally blocked out at 0 degrees  and had an extra
      mesiodistal gap set to 50 MUm. Then, zirconia crowns were fabricated, and their
      marginal and internal discrepancies were recorded with the silicone replica
      technique. All replicas were examined under a stereomicroscope at 50*
      magnification. Collected data were analyzed with one-way ANOVA and post hoc Tukey
      test for marginal fit. For the axial and incisal fit, measured values did not
      follow a normal distribution; therefore, the Kruskal-Wallis and the
      Dunn/Bonferroni multiple comparison tests were applied (p = 0.05). RESULTS: The
      mean marginal fit of -8 degrees  crowns (58.2 +/- 6.0 MUm) was statistically
      different (p < 0.0001) from all the remaining crowns (range 42.1-47.3 MUm). Also,
      the internal fit was statistically significant when comparing crowns fabricated
      over abutments with positive and negative TOC angles (p < 0.0001). The largest
      median axial discrepancies were found in the -8 degrees  (165.5 MUm) and -4
      degrees  (130.8 MUm) groups; however, when evaluating the incisal fit, they
      showed the smallest discrepancies (67.3 and 81.8 MUm, respectively). CONCLUSIONS:
      Under the conditions of this study, the marginal and internal fit of zirconia
      crowns fabricated over inverse-tapered preparations is within clinically accepted
      values.

PMID- 29194840
TI  - Parasites favour intermediate nestling mass and brood size in cliff swallows.
AB  - A challenge of life-history theory is to explain why animal body size does not
      continue to increase, given various advantages of larger size. In birds, body
      size of nestlings and the number of nestlings produced (brood size) have
      occasionally been shown to be constrained by higher predation on larger nestlings
      and those from larger broods. Parasites also are known to have strong effects on
      life-history traits in birds, but whether parasitism can be a driver for
      stabilizing selection on nestling body size or brood size is unknown. We studied
      patterns of first-year survival in cliff swallows (Petrochelidon pyrrhonota) in
      western Nebraska in relation to brood size and nestling body mass in nests under
      natural conditions and in those in which hematophagous ectoparasites had been
      removed by fumigation. Birds from parasitized nests showed highest first-year
      survival at the most common, intermediate brood-size and nestling-mass
      categories, but cliff swallows from nonparasitized nests had highest survival at
      the heaviest nestling masses and no relationship with brood size. A survival
      analysis suggested stabilizing selection on brood size and nestling mass in the
      presence (but not in the absence) of parasites. Parasites apparently favour
      intermediate offspring size and number in cliff swallows and produce the observed
      distributions of these traits, although the mechanisms are unclear. Our results
      emphasize the importance of parasites in life-history evolution.

PMID- 29194842
TI  - Mother's level of confidence in caring for her late preterm infant: A mixed
      methods study.
AB  - AIM AND OBJECTIVES: To examine what it means to be a mother of a late preterm
      infant including a mother's level of confidence in caring for her late preterm
      infant over time and the effect of maternal depression of this experience.
      BACKGROUND: Little is known about mothers' experiences of caring for their late
      preterm infants in the community, including their level of confidence and
      parenting stress within the context of a supported care environment by public
      health nurses. DESIGN: A mixed methods study, sequential explanatory quantitative
      and qualitative study. METHODS: A convenience sample of mothers with LPIs (n =
      71) completed questionnaires on maternal confidence (3-4 weeks and 6-8 weeks),
      parenting stress (6-8 weeks), social support (6-8 weeks) and postpartum
      depression (6-8 weeks). A purposive sample of mothers (n = 11) underwent in
      depth, semi-structured interviews. RESULTS: Maternal confidence decreased from 3
      4 weeks-6-8 weeks after delivery, and similar results were found for mothers who
      reported depressive symptoms. Narratives of the mothers suggested the decrease in
      maternal confidence over time was influenced by the demanding characteristics of
      the late preterm infant, the prospect of their rehospitalisation and the mother's
      reported interactions with public health nurses. Depression had an effect on
      maternal confidence; that is, the depressed mothers demonstrated less confidence
      about their caretaking role than the nondepressed mothers at 6-8 weeks. Mothers
      did not discuss mental health issues, which may reflect the protective effects of
      social support on emotional instability or an inability to recognise postpartum
      depression. CONCLUSION: The confidence of mothers with LPIs decreased over the
      first 2 months following delivery and being home with their infants. Assisting
      mothers to meet their personal needs and the needs of their infant should promote
      maternal skills, which will likely increase maternal confidence related to the
      care of their late preterm infant. RELEVANCE FOR CLINICAL PRACTICE:
      Characteristics of LPIs contributed more to parenting stress score than parent
      characteristics; mothers however attempted to normalise the late preterm infant
      in order to minimise the parenting stress. Evidence-informed brief interventions
      tailored based on late preterm infant and parent characteristics may improve
      maternal confidence over time. Healthcare professional should provide education
      and anticipatory guidance prior to discharge, consistent care in hospital and
      postdischarge as this may impact maternal level of confidence. Future research
      needs to examine standards of care for discharge of LPIs and adherence to these
      standards.

PMID- 29194843
TI  - Discovery of Potent EGFR Inhibitors through the Incorporation of a 3D-Aromatic
      Boron-Rich-Cluster into the 4-Anilinoquinazoline Scaffold: Potential Drugs for
      Glioma Treatment.
AB  - New 1,7-closo-carboranylanilinoquinazoline hybrids have been identified as EGFR
      inhibitors, one of them with higher affinity than the parent compound erlotinib.
      The comparative docking analysis with compounds bearing bioisoster-substructures,
      demonstrated the relevance of the 3D aromatic-boron-rich moiety for interacting
      into the EGFR ATP binding region. The capability to accumulate in glioma cells,
      the ability to cross the blood-brain barrier and the stability on simulated
      biological conditions, render these molecules as lead compounds for further
      structural modifications to obtain dual action drugs to treat glioblastoma.

PMID- 29194845
TI  - Weight loss in obese patients with longstanding persistent atrial fibrillation
      undergoing catheter ablation: Is it worth the trouble?

PMID- 29194844
TI  - Older Brazilian caregivers and their lived experiences of caring-A hermeneutic
      phenomenological study.
AB  - AIMS AND OBJECTIVES: To understand the lived experiences of older Brazilian
      carers. BACKGROUND: For many caregivers, the practice of caregiving becomes their
      daily lives, embedding in their care and the experiences, beliefs, learning and
      techniques that contribute to the meanings these caregivers attach to their
      world. Studies have reported on the experiences of caregivers in general;
      however, few studies have addressed the unique characteristics of older
      caregivers. METHOD: Phenomenological research was conducted in the homes of these
      persons who were registered in a public programme of home care. This study
      utilised recorded interviews with a guiding question and roadmap for
      characterisation. The transcribed interviews were analysed based on philosophical
      hermeneutics and on the understanding of the hermeneutic circle. The units of
      meaning were discussed from the perspective of Heidegger's phenomenology.
      RESULTS: Six older primary caregivers participated, aged between 62-84 years. The
      following units of meaning were developed: the daily life of being in the world
      as an older person caring for another older person, the historicity and their
      disclosedness to the world of care. CONCLUSIONS: The worldliness of these people
      is influenced by a taxing routine and being overloaded and lonely, which renders
      these caregivers vulnerable because of this routine and because of the inherent
      weaknesses induced by the ageing process. RELEVANCE TO CLINICAL PRACTICE: This
      research can help health professionals better understand the worldliness of older
      caregivers. Such understanding will enhance the assistance available to
      caregivers, which must extend beyond the care of the sick person: interventions
      can reduce their overburden and risk of illness, improving their experiences as
      caregivers and their quality of life.

PMID- 29194846
TI  - Supply-side effects from public insurance expansions: Evidence from physician
      labor markets.
AB  - Medicaid and the Child Health Insurance Programs (CHIP) are key sources of
      coverage for U.S. children. Established in 1997, CHIP allocated $40 billion of
      federal funds across the first 10 years but continued support required
      reauthorization. After 2 failed attempts in Congress, CHIP was finally
      reauthorized and significantly expanded in 2009. Although much is known about the
      demand-side policy effects, much less is understood about the policy's impact on
      providers. In this paper, we leverage a unique physician dataset to examine if
      and how pediatricians responded to the expansion of the public insurance program.
      We find that newly trained pediatricians are 8 percentage points more likely to
      subspecialize and as much as 17 percentage points more likely to enter private
      practice after the law passed. There is also suggestive evidence of greater
      private practice growth in more rural locations. The sharp supply-side changes
      that we observe indicate that expanding public insurance can have important
      spillover effects on provider training and practice choices.

PMID- 29194847
TI  - Clinical evaluation of the multifunctional suprapubic catheter in patients
      requiring permanent suprapubic cystostomy: a prospective randomized trial in a
      single center.
AB  - AIMS AND OBJECTIVES: To assess the clinical effect of the multifunctional
      suprapubic catheter (MSC) on occurrence of cystospasm, catheter occlusion, the
      catheter-related urinary tract infection and remission of over-activity bladder,
      by comparing with the conventional suprapubic catheter (CSC) in patients with
      permanent suprapubic cystostomy. BACKGROUND: The conventional suprapubic catheter
      usually presents with high incidence of catheter-associated complications.
      DESIGN: A prospective randomized clinical trial in a single-center. METHODS:
      Between Jan 2014 and Jan 2015, a total of 91 consecutive patients with permanent
      suprapubic cystostomy were prospectively randomized into two groups: the MSC
      group (n = 43) and CSC group (n = 48). RESULTS: Our results showed that the total
      times of cystospasm in the MSC group were significantly less than that in the CSC
      group during the follow-up time (p < 0.001). In addition, the mean spasmodic
      duration per time in the MSC group was significantly shorter than that in the CSC
      group (p < 0.001). Besides, catheter occlusions were observed in 23 (25.27%)
      patients, including 5 (11.63%) in the MSC group and 18 (37.50%) in the CSC group
      (p = 0.005). The lower rate of positive urine culture was also found in the MSC
      group but with no significant difference (p = 0.540). Furthermore, the urodynamic
      measurement data demonstrated that the patients in the MSC group had a greater
      remission rate of over-activity bladder after catheter change (p < 0.001).
      CONCLUSIONS: The present data showed that the multifunctional suprapubic catheter
      could significantly reduce the incidence of catheter occlusion, ameliorate the
      symptom of cystospasm and relieve the over-activity bladder, but have no
      influence on the catheter-related urinary tract infection. This article is
      protected by copyright. All rights reserved.

PMID- 29194848
TI  - Natural regulatory IgM-mediated autoimmune responses directed against
      malondialdehyde regulate oxidative and nitrosative pathways and coupled with IgM
      responses to nitroso adducts attenuate depressive and physiosomatic symptoms at
      the end of term pregnancy.
AB  - AIM: We aimed to delineate the effects of immunoglobulin (Ig)M-mediated
      autoimmune responses directed against malondialdehyde (MDA) and nitroso (SNO)
      adducts on nitro-oxidative stress and depressive and physiosomatic symptoms
      (DPSS) at the end of term. METHODS: IgM responses to MDA, NO (nitroso) adducts
      formed by nitrosylation, and NO2 tyrosine formed by nitration were measured as
      well as hydroperoxides (ferrous oxidation xylenol orange), advanced protein
      oxidation products (AOPP), and NO metabolite (NOx) levels in women at the end of
      term pregnancy and in normal controls. RESULTS: IgM responses to MDA were
      significantly and inversely associated with AOPP, ferrous oxidation xylenol
      orange, and NOx and DPSS. IgM responses to NO adducts were significantly and
      inversely associated with DPSS and positively with NOx levels. There were
      significant associations between IgM responses to MDA, NO adducts, and NO2
      tyrosine. The DPSS score was predicted by AOPP and a lifetime history of
      premenstrual syndrome (both positively) and IgM responses to NO adducts
      (inversely). Furthermore, 71.8% of the variance in the index of nitro-oxidative
      stress was explained by lowered IgM responses to MDA, antioxidant levels (zinc,
      total radical trapping parameter), and inflammatory mediators. CONCLUSION:
      Lowered levels of IgM responses to MDA during pregnancy are accompanied by a
      reduced regulation of nitro-oxidative processes thereby explaining increased
      oxidative and nitrosative stress biomarkers in association with DPSS. IgM
      responses to NO adducts, which reflect nitrosylation as a consequence of
      increased NO production, regulate DPSS symptoms at the end of term and are a
      trait marker of major depression. IgM responses to MDA are a key part of the
      compensatory anti-inflammatory responses system.

PMID- 29194849
TI  - Somatotopic effects of rTMS in neuropathic pain? A comparison between stimulation
      over hand and face motor areas.
AB  - BACKGROUND: The therapeutic influence of somatotopic matching between pain
      topography and motor cortex stimulation site for neuropathic pain (NP) remains
      controversial. METHODS: Thirty-two patients suffering from NP involving the upper
      limb (n = 20) or the face (n = 12) received two high-frequency rTMS
      neuronavigated sessions targeting hand and face motor cortical areas, versus
      placebo. The cortical target was defined by anatomical MRI and EMG responses in
      all patients, completed in 19 of them by functional MRI. Sessions were separated
      by at least 2 weeks and applied in random order. Pain relief was assessed using
      numerical rating scale (NRS). RESULTS: In terms of percentage of pain relief,
      rTMS over the hand motor area was significantly superior to both face rTMS and
      placebo. When comparing pre- and post-NRS scores, a significant decrease in pain
      was observed after hand area rTMS for the two pain localizations, while
      stimulation of the face area induced a slight but nonsignificant effect on upper
      limb pain after correction. Sham-rTMS did not exert any effect. The percentage of
      patients with clinically significant (>30%) or mild (15-30%) pain relief did not
      differ, however, between rTMS addressed to the hand or face area. CONCLUSIONS:
      The results do not support a somatotopic effect of motor rTMS for NP. Lack of
      clinically relevant somatotopic effects in upper limb or face pain suggests that
      much of the rTMS analgesic effect may depend on high-order mechanisms involving
      cognitive and affective appraisal of pain, rather than on a sensory effect
      related to the specific motor area stimulated. SIGNIFICANCE: Strict somatotopic
      targeting of rTMS does not appear warranted for the treatment of upper limb or
      face NP. Since the hand motor area is easier to target and provides better
      results, it might be privileged for both types of pain.

PMID- 29194850
TI  - The third person in the room: The needs of care partners of older people in home
      care services-A systematic review from a person-centred perspective.
AB  - AIMS AND OBJECTIVES: To identify and synthesise the needs of care partners of
      older people living at home with assistance from home care services. BACKGROUND:
      "Ageing in place" is a promoted concept where care partners and home care
      services play significant roles. Identifying the needs of care partners and
      finding systematic ways of meeting them can help care partners to cope with their
      role. DESIGN/METHODS: This study is based on the PRISMA reporting guidelines. The
      systematic review of qualitative and quantitative studies was guided by the
      Joanna Briggs Institute methodology. RESULTS: In total, 16 studies were included
      in the review, eleven qualitative and five quantitative. Three main categories
      were revealed in the analysis: the need for quality interaction, the need for a
      shared approach to care and the need to feel empowered. CONCLUSION: Care partners
      of older people have several, continuously unmet needs. A person-centred
      perspective can contribute new understandings of how to meet these needs. A
      knowledge gap has been identified regarding the needs of care partners of older
      people with mental health problems. There is a need to develop a tool for
      systematic collaboration between home care services and care partners, so that
      the identified needs can be met in a more thorough, systematic and person-centred
      way. RELEVANCE TO CLINICAL PRACTICE: The carers in home care services need
      competence to identify and meet the needs of care partners. The implementation of
      person-centred values in home care services can contribute to meet the needs of
      care partners to a greater extent than today. Future research on the needs of
      care partners of older people with mental health problems needs to be undertaken.

PMID- 29194851
TI  - Superiority of capsaicin 8% patch versus oral pregabalin on dynamic mechanical
      allodynia in patients with peripheral neuropathic pain.
AB  - BACKGROUND: Dynamic Mechanical Allodynia (DMA) is a typical symptom of
      neuropathic pain (NP). In a recent study, the capsaicin 8% patch was noninferior
      to pregabalin in overall peripheral NP relief. In this study, we report the
      comparison of the two treatments in relieving DMA. METHODS: In a randomized, open
      label, head-to-head, 8-week study, 488 patients with peripheral NP were treated
      with the capsaicin 8% patch (one application) or an optimized dose of pregabalin.
      Assessments included the area and intensity of DMA, and the number of patients
      achieving complete resolution of DMA. RESULTS: At baseline, 253 patients in the
      capsaicin 8% patch group and 235 patients in the pregabalin group had DMA. From
      baseline to end of study, the change in DMA intensity was significantly in favour
      of the capsaicin 8% patch versus pregabalin [-0.63 (95% CI: -1.04, -0.23; p =
      0.002)]. Similarly, the capsaicin 8% patch was superior to pregabalin in reducing
      the area of DMA [-39.5 cm2 (95% CI: -69.1, -10.0; p = 0.009)] from baseline to
      end of study. Overall, a greater proportion of patients had a complete resolution
      of allodynia with capsaicin 8% patch treatment compared with pregabalin treatment
      (24.1% vs. 12.3%; p = 0.001) at end of study. CONCLUSION: Capsaicin 8% treatment
      was superior to pregabalin in reducing the intensity and area of DMA, and in the
      number of patients with complete resolution of DMA. SIGNIFICANCE: The superiority
      of a topical treatment over pregabalin in relieving DMA supports the view that
      both peripheral and central sensitization can mediate allodynia.

PMID- 29194852
TI  - The role of sclerostin/dickkopf-1 and receptor activator of nuclear factor kB
      ligand/osteoprotegerin signalling pathways in the development of osteoporosis in
      patients with haemophilia A and B: A cross-sectional study.
AB  - AIM: Haemophilia A and B are associated with reduced bone mineral density (BMD).
      The aim of this study was to assess circulating sclerostin and dickkopf-1 (Dkk
      1), (inhibitors of osteoblastic differentiation), as well as the receptor
      activator of nuclear factor kB ligand (RANKL)/osteoprotegerin (OPG) system (the
      major regulator of osteoclastogenesis), in patients with haemophilia (PWH), their
      possible correlations with clinical risk factors and the effect of ibandronate on
      these markers. METHODS: Eighty-nine male PWH (mean age 45.9 +/- 15.3 years) and
      30 age-matched healthy male controls participated. BMD was assessed by DXA.
      Sclerostin, Dkk-1, RANKL and OPG were measured in serum of patients, controls, as
      well as in ten patients receiving oral ibandronate (150 mg/mo), at baseline and
      after 12 months. RESULTS: Patients with haemophilia had lower circulating
      sclerostin (median +/- IQR: 47.4 +/- 26.93 vs 250 +/- 250 pmol/L, P < .001), Dkk
      1 (21.24 +/- 17.18 vs 26.16 +/- 15.32pg/mL, P = .04) and higher levels of RANKL
      (0.23 +/- 0.03 vs 0.04 +/- 0.03 pmol/L, P = .001), RANKL/OPG ratio (0.063 +/-
      0.25 vs 0.005 +/- 0.11, P = .001) compared with controls. Patients with low BMD
      had higher OPG concentrations compared to those with normal BMD. Sclerostin and
      RANKL/OPG correlated positively with BMD. Patients with severe haemophilia had
      lower sclerostin concentrations compared with those with mild or moderate
      disease. The degree of arthropathy negatively correlated with sclerostin and Dkk
      1 levels. PWH who received ibandronate showed a decrease in serum Dkk-1 without
      any significant effect on sclerostin and RANKL/OPG. CONCLUSIONS: Patients with
      haemophilia present increased osteoclastic activity coupled with compensatory
      increased osteoblastic activity. Ibandronate did not affect RANKL/OPG ratio, but
      it decreased Dkk-1.

PMID- 29194853
TI  - Report on the 2nd European Tissue Repair Society summer school, Brussels,
      September 11-12th, 2017.

PMID- 29194854
TI  - Vessel noise cuts down communication space for vocalizing fish and marine
      mammals.
AB  - Anthropogenic noise across the world's oceans threatens the ability of vocalizing
      marine species to communicate. Some species vocalize at key life stages or whilst
      foraging, and disruption to the acoustic habitat at these times could lead to
      adverse consequences at the population level. To investigate the risk of these
      impacts, we investigated the effect of vessel noise on the communication space of
      the Bryde's whale Balaenoptera edeni, an endangered species which vocalizes at
      low frequencies, and bigeye Pempheris adspersa, a nocturnal fish species which
      uses contact calls to maintain group cohesion while foraging. By combining long
      term acoustic monitoring data with AIS vessel-tracking data and acoustic
      propagation modelling, the impact of vessel noise on their communication space
      was determined. Routine vessel passages cut down communication space by up to
      61.5% for bigeyes and 87.4% for Bryde's whales. This influence of vessel noise on
      communication space exceeded natural variability for between 3.9 and 18.9% of the
      monitoring period. Additionally, during the closest point of approach of a large
      commercial vessel, <10 km from the listening station, the communication space of
      both species was reduced by a maximum of 99% compared to the ambient soundscape.
      These results suggest that vessel noise reduces communication space beyond the
      evolutionary context of these species and may have chronic effects on these
      populations. To combat this risk, we propose the application or extension of ship
      speed restrictions in ecologically significant areas, since our results indicate
      a reduction in sound source levels for vessels transiting at lower speeds.

PMID- 29194855
TI  - Regarding Wellness and Burnout Initiatives in Emergency Medicine.

PMID- 29194856
TI  - Toronto Clinical Neuropathy Score is valid for a wide spectrum of
      polyneuropathies.
AB  - BACKGROUND AND PURPOSE: The Toronto Clinical Neuropathy Score (TCNS) is a valid
      and reliable scale for the diagnosis and staging of diabetic sensorimotor
      polyneuropathy. In this study, we aimed to explore the performance of the TCNS in
      non-diabetic polyneuropathies. METHODS: We performed a prospective study from
      November 2016 to May 2017 of patients with non-diabetic polyneuropathy. Patients
      had clinical, electrophysiological and functional assessments of their
      polyneuropathy, and the findings were correlated with the TCNS. RESULTS: The TCNS
      correlated with all clinical, electrophysiological and disability measures of
      polyneuropathy, mostly at a moderate level (e.g. r = -0.58 for sural nerve action
      potential amplitude). Higher TCNS severity grades were associated with worse
      polyneuropathy on all measures in the lower limbs, and with worse
      electrophysiological parameters and vibration perception thresholds in the upper
      limbs. The scale also showed excellent reliability and accuracy (kappa, 0.92-0.93
      for inter- and intra-observer reliability; area under the receiver operating
      characteristics curve, 0.93). CONCLUSION: The TCNS is a valid and reliable scale
      for a wide spectrum of polyneuropathies, and might be useful in clinical practise
      and research for the diagnosis and staging of polyneuropathy.

PMID- 29194857
TI  - Computed tomographic characteristics of pneumolabyrinth in a French bulldog with
      otitis media and externa.
AB  - A four-year-old female French bulldog was presented for evaluation of acute, left
      sided peripheral vestibular syndrome. Computed tomographic (CT) examination of
      the head revealed the presence of air within the left cochlea and vestibule,
      consistent with pneumolabyrinth. This was concurrent with ipsilateral otitis
      media and externa. Pneumolabyrinth is an uncommon finding in humans and is most
      frequently due to head trauma and temporal bone fracture. This is the first
      report describing pneumolabyrinth in a dog, apparently of nontraumatic origin in
      this case.

PMID- 29194859
TI  - A nationwide epidemiological study of myasthenia gravis in Latvia.
AB  - BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disorder
      characterized by fatigable muscle weakness due to antibody-mediated impairment of
      neuromuscular transmission. The aim of this study was to investigate the
      incidence and prevalence of MG in Latvia, and to characterize this population by
      well-established clinical parameters such as age at onset, presence of associated
      antibodies and thymus pathology. METHODS: All prevalent cases on 1 January 2015
      and cases of patients newly presenting with MG symptoms from 1 January 2010 to 31
      December 2014 were selected from the database of the Neuromuscular Disease Clinic
      of Pauls Stradins Clinical University Hospital and Children's Clinical University
      Hospital. Crude rates were calculated based on population data. These were
      directly age-standardized to the European and World Health Organization world
      standard populations. The analysis of clinical characteristics was carried out in
      a cohort of patients who had undergone a complete set of electrophysiological,
      serological and radiological investigations (n = 153; 68%). RESULTS: During the
      study period 99 incident and 226 prevalent cases were identified. The total crude
      MG incidence was 9.7 per million person-years. The prevalence of MG on 1 January
      2015 was 113.8 per million. 54.2% of patients tested positive for acetylcholine
      receptor antibodies, 7.8% for muscle specific kinase antibodies and 1.3% for
      lipoprotein related protein 4 antibodies. CONCLUSIONS: This is the first study of
      MG in Latvia and the second population-based study of MG in Eastern Europe. Our
      epidemiological results are similar to those in some other European and Northern
      American countries, and show high prevalence and increasing incidence of late
      onset MG.

PMID- 29194858
TI  - Low incidence of hepatitis B virus reactivation and subsequent hepatitis in
      patients with chronic hepatitis C receiving direct-acting antiviral therapy.
AB  - To determine the clinical characteristics of hepatitis B virus (HBV) reactivation
      in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we
      examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved
      HBV infection during and after treatment with direct-acting antiviral agents
      (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was
      administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients
      and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167
      patients with genotype 2 were treated with SOF plus ribavirin. Three patients
      with an HBV DNA level >=2000 IU/mL were treated with entecavir before anti-HCV
      therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen
      (HBsAg)-positive patients with an HBV DNA level <2000 IU/mL, the viral load
      increased during treatment. However, hepatitis flare did not occur in these
      patients. There was no significant difference in clinical history between
      patients with and without HBV reactivation. Among 765 patients with resolved HBV
      infection, HBV reactivation occurred in 1 (0.1%) patient after initial
      resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We
      compared anti-HBs titres at baseline with those at post-DAA therapy in 123
      patients without HBsAg. There was no significant difference in anti-HBs levels
      between the two points (P = .79). In conclusion, HBV reactivation was rare in
      HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not
      occur in HBV-reactivated patients with a baseline HBV DNA level <2000 IU/mL
      before DAA therapy.

PMID- 29194860
TI  - Cobalt-Catalyzed Enantioselective Negishi Cross-Coupling of Racemic alpha-Bromo
      Esters with Arylzincs.
AB  - The first cobalt-catalyzed enantioselective Negishi cross-coupling reaction, and
      the first arylation of alpha-halo esters with arylzinc halides, are disclosed.
      Employing a cobalt-bisoxazoline catalyst, various alpha-arylalkanoic esters were
      synthesized in excellent enantioselectivities and yields (up to 97 % ee and 98 %
      yield). A diverse range of functional groups, including ether, halide, thioether,
      silyl, amine, ester, acetal, amide, olefin and heteroaromatics is tolerated by
      this method. This method was suitable for gram-scale reactions, enabling the
      synthesis of (R)-xanthorrhizol with high enantiopurity. Radical clock experiments
      support the intermediacy of radicals.

PMID- 29194862
TI  - A case report: Is mexiletine usage effective in the shortening of QTC interval
      and improving the T-wave alternans in Timothy syndrome?
AB  - Timothy syndrome (TS) is a multisystemic disease that occurs because of a
      mutation in CACN1C gene and is characterized by prolonged QT interval. Mexiletine
      is a Class 1B antiarrhythmic drug that causes the disappearance of T-wave
      alternans by shortening QTc and peak-to-end of the T wave. It may block the
      development of torsades de pointes in a prolonged QT. This study presented the
      case of a patient diagnosed with TS and had a cardiac arrest history, prolonged
      QT, and T-wave alternans. After mexiletine treatment, the QTc interval shortened
      and T-wave alternans disappeared. Such a case has rarely been seen in the
      literature, and hence considered rare. This case presentation was of particular
      importance because it highlighted the use of mexiletine besides an initial beta
      blocker treatment in the cases with TS.

PMID- 29194861
TI  - Trends in hepatocellular carcinoma incidence and survival among people with
      hepatitis C: An international study.
AB  - This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular
      carcinoma (HCC) incidence and survival in three settings, prior to introduction
      of direct-acting antiviral (DAA) therapies. HCV notifications from British
      Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995
      2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital
      admissions (2001-2012/2013/2014, respectively) and mortality (1995
      2013/2014/2015, respectively). Age-standardized HCC incidence rates were
      evaluated, associated factors were assessed using Cox regression, and median
      survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924
      people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%)
      had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all
      jurisdictions. Age-standardized HCC incidence rates remained stable in BC and
      Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older
      age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93,
      10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis
      remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years
      in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to
      1.5 years in 2007-2014). Across the settings, HCC burden increased, individual
      level risk of HCC remained stable or increased, and HCC survival remained
      extremely low. These findings highlight the minimal impact of HCC prevention and
      management strategies during the interferon-based HCV treatment era and form the
      basis for evaluating the impact of DAA therapy in the coming years.

PMID- 29194863
TI  - Associations of stream geomorphic conditions and prevalence of alternative
      reproductive tactics among sockeye salmon populations.
AB  - In many species, males may exhibit alternative life histories to circumvent the
      costs of intrasexual competition and female courtship. While the evolution and
      underlying genetic and physiological mechanisms behind alternative reproductive
      tactics are well studied, there has been less consideration of the ecological
      factors that regulate their prevalence. Here, we examine six decades of age
      composition records from thirty-six populations of sockeye salmon (Oncorhynchus
      nerka) to quantify associations between spawning habitat characteristics and the
      prevalence of precocious sneakers known as 'jacks'. Jack prevalence was
      independent of neutral genetic structure among stream populations, but varied
      among habitat types and as a function of continuous geomorphic characteristics.
      Jacks were more common in streams relative to beaches and rivers, and their
      prevalence was negatively associated with stream width, depth, elevation, slope
      and area, but positively related to bank cover. Behavioural observations showed
      that jacks made greater use of banks, wood and shallows than guard males,
      indicating that their reproductive success depends on the availability of such
      refuges. Our results emphasize the role of the physical habitat in shaping
      reproductive tactic frequencies among populations, likely through local
      adaptation in response to variable fitness expectations under different
      geomorphic conditions.

PMID- 29194864
TI  - Comparison of outpatient and home-based exercise training programmes for COPD: A
      systematic review and meta-analysis.
AB  - Chronic obstructive pulmonary disease is a common, preventable and treatable
      disease. Exercise training programmes (ETPs) improve symptoms, health-related
      quality of life (HRQoL) and exercise capacity, but the optimal setting is
      unknown. In this review, we compared the effects of ETPs in different settings on
      HRQoL and exercise capacity. We searched (5 July 2016) the Cochrane Airways Group
      Specialised Register, ClinicalTrials.gov and World Health Organization trials
      portal. We selected studies, extracted data and assessed risk of bias with two
      independent reviewers. We calculated mean differences (MD) with 95% CI. We
      assessed the quality of evidence using Grades of Recommendation, Assessment,
      Development and Evaluation. Ten trials (934 participants) were included. Hospital
      (outpatient) and home-based ETPs (seven trials) were equally effective at
      improving HRQoL on the Chronic Respiratory Questionnaire (CRQ) (dyspnoea: MD 
      0.09, 95% CI: -0.28 to 0.10; fatigue: MD -0.00, 95% CI: -0.18 to 0.17; emotional:
      MD 0.10, 95% CI: -0.24 to 0.45; and mastery: MD -0.02, 95% CI: -0.28 to 0.25;
      moderate quality) and on the St George's Respiratory Questionnaire (SGRQ) (MD 
      0.82, 95% CI: -7.47 to 5.83, low quality). Hospital (outpatient) and community
      based ETPs (three trials) were equally effective at improving HRQoL (CRQ
      dyspnoea: MD 0.29, 95% CI: -0.05 to 0.62, moderate quality; fatigue: MD -0.02,
      95% CI: -1.09 to 1.05, low quality; emotional: MD 0.10, 95% CI: -0.40 to 0.59,
      moderate quality; and mastery: MD -0.08, 95% CI: -0.45 to 0.28, moderate
      quality). There was no difference in exercise capacity. There was low to moderate
      evidence that outpatient and home-based ETPs are equally effective. See related
      Editorial.

PMID- 29194865
TI  - Finasteride accelerates prostate wound healing after thulium laser resection
      through DHT and AR signalling.
AB  - OBJECTIVES: Urinary tract infection, urinary frequency, urgency, urodynia and
      haemorrhage are common post-operative complications of thulium laser resection of
      the prostate (TmLRP). Our study mainly focuses on the role of finasteride in
      prostate wound healing through AR signalling. MATERIALS AND METHODS: TmLRP
      beagles were randomly distributed into different treatment groups. Serum and
      intra-prostatic testosterone and DHT level were determined. Histological analysis
      was conducted to study the re-epithelialization and inflammatory response of the
      prostatic urethra in each group. We investigated the role of androgen in
      proliferation and inflammatory response in prostate. In addition, the effects of
      TNF-alpha on prostate epithelium and stromal cells were also investigated.
      RESULTS: Testosterone and DHT level increased in testosterone group and DHT
      decreased in finasteride group. Accelerated wound healing of prostatic urethra
      was observed in the finasteride group. DHT suppressed proliferation of prostate
      epithelium and enhanced inflammatory response in prostate. We confirmed that DHT
      enhanced macrophages TNF-alpha secretion through AR signalling. TNF-alpha
      suppressed proliferation of prostate epithelial cells and retarded cell
      migration. TNF-alpha also played a pivotal role in suppressing fibroblasts
      activation and contraction. CONCLUSION: Testosterone treatment repressed re
      epithelialization and wound healing of prostatic urethra. Finasteride treatment
      may be an effective way to promote prostate re-epithelialization.

PMID- 29194866
TI  - Break-through bleeding in relation to pharmacokinetics of Factor VIII in
      paediatric patients with severe haemophilia A.
AB  - INTRODUCTION: As the pharmacokinetics (PK) of factor VIII (FVIII) is
      individualized in children with haemophilia A (HA), PK parameters may be
      indicators of patients' bleeding phenotype and instruction for their personalized
      replacement program. AIM: The aim of this study was to investigate the possible
      relationship between PK/FVIII level and bleeding frequency in Chinese paediatric
      patients with severe (HA). METHODS: A total of 24 patients were enrolled in
      Beijing Children's Hospital from February to October 2015, all of whom were given
      50 IU/kg of FVIII concentrates after a 72-hours washout period. Samples'
      activities (FVIII:C) were tested at 5 time points, using WinNonlin software for
      PK testing, and then the individual half-life(t1/2 ) and the time (h) of FVIII
      concentrations <1 IU/dL within a week during prophylaxis were calculated.
      Baseline and the annual bleeding rate (ABR), annual joint bleeding rate (AJBR)
      were recorded and analyzed. RESULTS: The mean t1/2 of FVIII was 10.20 +/- 2.72
      hours and the mean time of FVIII <1 IU/dL in 1 week was 44.7 hours (-38.56 to
      102.33 hours). A significant relationship between t1/2 of FVIII and ABR0 /AJBR0
      (baseline bleeding) was found (R2  = 0.75 and 0.62, P < .001). Besides, baseline
      and the annual bleeding rate during prophylactic treatment of haemophilia had a
      positive correlation with the time (hours) of FVIII <1 IU/dL in 1 week (R2  =
      0.67 and 0.52, P < .001). CONCLUSION: t1/2 was an important indicator to prevent
      bleeding in severe HA; the frequency of bleeding will be reduced with the
      increased of t1/2 of FVIII. The data also demonstrates that increasing the time
      with a FVIII<1 IU/dL is associated with an increased rate of bleeding during
      prophylaxis.

PMID- 29194867
TI  - Relationship between Hammett's parameters and in silico density functional with
      tandem mass ESI-CID fragmentation: Dihydropyridines as prototypes.
AB  - Over the years, with the instrumental analysis evolution, the relationships
      between the carried-out results with the data of theoretical analysis in silico
      and the Hammett's parameters have been reported. They have been very useful for
      chemical characterization of small organic molecules. Thus, this work aims at
      showing the feasibility and limitations for Hammett's and density functional
      theory applications in electrospray ionization-collision-induced dissociation
      (ESI-CID) fragmentation provision. For this, 13 dihydropyrimidinones para, meta,
      and orto monosubstituted were studied using ESI and CID in positive mode. As a
      result, it was observed that the main fragmentation includes the isocyanate and
      ethanol loses at low energy. Nevertheless, at higher energies, radical ions
      formed by McLafferty rearrangement were observed. The Hammett plots were
      correlated fragmentation profiles, showing good linearity for the [M + H]+ ,
      which does not occur to radical ions and carbocation's. These tendencies had
      demonstrated that the stability of protonate and activation energy of secondary
      ions changes with the pKa. The density functional theory studies indicated that,
      both nitrogen atoms in the dihydropyrimidinone's prototypes are capable of being
      protonated. However, the activation energy of fragmentation products is not
      changed. Therefore, this work has shown information, which can be useful to
      understand tandem mass spectrometry in ESI-CID conditions for small organic
      molecules series. This is the first step for normalization of fragmentation
      pathway.

PMID- 29194868
TI  - Narrowing filtered QRS duration on signal-averaged electrocardiogram predicts
      outcomes in cardiac resynchronization therapy patients with nonischemic heart
      failure.
AB  - BACKGROUND: To evaluate the impact of changes in the filtered QRS duration (fQRS)
      on signal-averaged electrocardiograms (SAECGs) from pre- to postimplantation on
      the clinical outcomes in nonischemic heart failure (HF) patients under cardiac
      resynchronization therapy (CRT). METHODS: We studied 103 patients with
      nonischemic HF and sinus rhythm who underwent CRT implantation. SAECGs were
      obtained within 1 week before and 1 week after implantation and narrowing fQRS
      was defined as a decrease in fQRS from pre- to postimplantation. Echocardiography
      was performed before and 6 months after CRT implantation. The primary outcome was
      death from any cause. The secondary outcomes were hospitalization due to worsened
      HF and occurrence of ventricular tachyarrhythmias. RESULTS: Of the 103 CRT
      patients, 53 (51%) showed narrowing fQRS. Left ventricular end-diastolic volume
      and end-systolic volume were significantly reduced (both p < .001), and the left
      ventricular ejection fraction was significantly increased (p < .001) after CRT in
      patients with narrowing fQRS, but not in patients with nonnarrowing fQRS. During
      a median follow-up period of 33 months, patients with narrowing fQRS exhibited
      better survival than patients with nonnarrowing fQRS (p = .007). A lower
      incidence of hospitalization due to worsened HF (p < .001) and a lower occurrence
      of ventricular tachyarrhythmias (p = .071) were obtained in patients with
      narrowing fQRS. After adjusting for confounding variables, narrowing fQRS was
      associated with a low risk of mortality (HR 0.27, p = .006). CONCLUSION: Our
      results suggested that narrowing fQRS on SAECG after CRT implantation predicts LV
      reverse remodeling and long-term outcomes in nonischemic HF patients.

PMID- 29194869
TI  - Muscle strength and motor function throughout life in a cross-sectional cohort of
      180 patients with spinal muscular atrophy types 1c-4.
AB  - BACKGROUND AND PURPOSE: Natural history studies in spinal muscular atrophy (SMA)
      have primarily focused on infants and children. Natural history studies
      encompassing all age groups and SMA types are important for the interpretation of
      treatment effects of recently introduced survival motor neuron gene-augmenting
      therapies. METHODS: We conducted a cross-sectional study to investigate muscle
      strength, Hammersmith Functional Motor Scale (Expanded) score and the patterns of
      muscle weakness in relation to age and SMA type. RESULTS: We included 180
      patients with SMA types 1-4 in the age range 1-77.5 years with median disease
      duration of 18 (range 0-65.8) years. With the exception of the early phases of
      disease in which children with SMA types 2 and 3 may achieve new motor skills and
      show a temporary increase in muscle strength, cross-sectional data suggested that
      declining muscle strength and loss of motor skills over time are characteristic
      of all SMA types. Mean loss of strength was at least 1 point on the Medical
      Research Council score and 0.5 point on the Hammersmith Functional Motor Scale
      (Expanded) score per year. Trend lines compatible with deterioration of motor
      function and muscle strength started in childhood and continued into adulthood.
      The age at loss of specific motor skills was associated with disease severity.
      Triceps, deltoid, iliopsoas and quadriceps were the weakest muscles in all
      patients. Hierarchical cluster analysis did not show a segmental distribution of
      muscle weakness as suggested previously. CONCLUSIONS: Progressive muscle weakness
      and loss of motor function are characteristic of all SMA types and all ages.

PMID- 29194870
TI  - Delayed viral suppression during antiviral therapy is associated with increased
      hepatocellular carcinoma rates in HBeAg-positive high viral load chronic
      hepatitis B.
AB  - The treatment option in chronic hepatitis B (CHB) patients with persistent low
      level viremia despite entecavir or tenofovir monotherapy is unclear. This study
      investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in
      hepatitis B e antigen (HBeAg)-positive high viral load CHB patients, according to
      the time needed to achieve complete viral suppression. A total of 325 HBeAg
      positive CHB patients with high viral load who were recently started on antiviral
      therapy with entecavir or tenofovir were included. The enrolled patients were
      divided into 2 groups with 4 separate criteria based on the time needed to
      achieve complete viral suppression: within 1, 2, 3 or 4 years of therapy
      initiation. The outcomes were development of HCC and cirrhosis. The cumulative
      incidence of HCC was significantly higher in patients failing complete viral
      suppression within 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI),
      1.03-19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24-9.23; P = .018), than
      patients who achieved complete viral suppression within 1 or 2 years,
      respectively. Cumulative incidence of cirrhosis was also significantly higher in
      patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04-3.66; P =
      .037) or 2 years (HR, 2.44; 95% CI, 1.41-4.22; P = .001). When the time for
      achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or
      cirrhosis was not different regardless of viral suppression. Complete hepatitis B
      virus suppression within 2 years of antiviral therapy initiation is associated
      with risk reduction in HCC or cirrhosis development.

PMID- 29194871
TI  - Are you better? A multi-centre study of patient-defined recovery from Complex
      Regional Pain Syndrome.
AB  - BACKGROUND: Complex Regional Pain Syndrome (CRPS) symptoms can significantly
      differ between patients, fluctuate over time, disappear or persist. This leads to
      problems in defining recovery and in evaluating the efficacy of therapeutic
      interventions. OBJECTIVES: To define recovery from the patients' perspective and
      better understand their priorities for treatment approaches. METHODS:
      Establishing an international consortium, we used a 2-Round Delphi-based study in
      eight countries across Europe and North America. Participants >=18 years who met,
      or had met, Budapest clinical criteria were included. Round 1 participants
      completed the statement: 'I would/do consider myself recovered from CRPS
      if/because...' alongside demographic and health questionnaires. Data were
      thematically organised and represented as 62 statements, from which participants
      identified and ranked their recovery priorities in Round 2. RESULTS: Round 1 (N =
      347, 80% female, 91% non-recovered) dominant ICF themes were: activities of daily
      living; bodily functions; external factors; participation and personal factors.
      The top five priority statements in Round 2 (N = 252) were: no longer having (1)
      CRPS-related pain, (2) generalised pain and discomfort, (3) restricted range of
      movement, (4) need for medication, (5) stiffness in the affected limb. With very
      few exceptions, priorities were consistent, irrespective of patient
      demographics/geography. Symptoms affecting daily activities were among those most
      frequently reported. CONCLUSIONS: Our data showed a small number of themes are of
      highest importance to CRPS patients' definition of recovery. Patients want their
      pain, movement restriction and reliance on medication to be addressed, above all
      other factors. These factors should therefore be foremost concerns for future
      treatment and rehabilitation programmes. SIGNIFICANCE: Those with longstanding
      CRPS may no longer meet diagnostic criteria but still be symptomatic. Defining
      recovery is therefore problematic in CRPS. Our study has identified patients'
      definition of recovery from CRPS, in order of priority, as relief from: their
      CRPS-related pain, generalised pain, movement restriction, reliance on
      medication, and stiffness.

PMID- 29194872
TI  - Renal function up to the 5th decade of life after nephrectomy in childhood: A
      literature review.
AB  - The aim of the present study was to find out if in children ablation of 50% of
      renal mass may be associated with a progressive renal damage (Brenner's
      hypothesis). We collected 1035 adult or adolescent survivors who underwent
      nephrectomy for unilateral oncological or non-oncological causes during
      childhood. Stratification of all survivors for age revealed that the number of
      subjects with blood hypertension and/or renal dysfunction (glomerular filtration
      rate < 90 mL/min per 1.73 m2 ) to be significantly higher in survivors >=30 years
      old in comparison with younger patients. Available data on long-term renal
      function after nephrectomy during childhood support the Brenner's hypothesis.

PMID- 29194873
TI  - Stable NCNgNSi (Ng=Kr, Xe, Rn) Compounds with Covalently Bound C-Ng-N Unit:
      Possible Isomerization of NCNSi through the Release of the Noble Gas Atom.
AB  - Although the noble gas (Ng) compounds with either Ng-C or Ng-N bonds have been
      reported in the literature, compounds containing both bonds are not known. The
      first set of systems having a C-Ng-N bonding unit is predicted herein through the
      analysis of stability and bonding in the NCNgNSi (Ng=Kr-Rn) family. While the Xe
      and Rn inserted analogues are thermochemically stable with respect to all
      dissociation channels, but for the one producing CNSiN and free Ng, NCKrNSi has
      another additional three-body dissociation channel, NCKrNSi->CN+Kr+NSi, which is
      exergonic by -9.8 kcal mol-1 at 298 K. This latter dissociation can be hindered
      by lowering the temperature. Moreover, the NCNgNSi->Ng+CNSiN dissociation is also
      kinetically prohibited by a quite high free energy barrier ranging from 25.2 to
      39.3 kcal mol-1 , with a gradual increase in going from Kr to Rn. Therefore,
      these compounds are appropriate candidates for experimental realization. A
      detailed bonding analysis by employing natural bond orbital, electron density,
      energy decomposition, and adaptive natural density partitioning analyses
      indicates that both Ng-N and C-Ng bonds in the title compounds are covalent in
      nature. In fact, the latter analysis indicates the presence of delocalized 3c-3e
      sigma-bond within the C-Ng-N moiety and a totally delocalized 5c-2e sigma-bond in
      these compounds. This is an unprecedented bonding characteristic in the sense
      that the bonding pattern in Ng inserted compounds is generally represented as the
      presence of covalent bond in one side of Ng, and the ionic interaction in the
      other side. Further, the dissociation of Ng from NCNgNSi facilitates the
      formation of a higher energy isomer of NCNSi, CNSiN, which cannot be formed from
      bare NCNSi as such, because of the very high free energy barrier associated with
      the isomeric transformation. Therefore, in the presence of Ng atoms it might be
      possible to detect the high energy isomer.

PMID- 29194874
TI  - Late-onset severe long QT syndrome.
AB  - We report a case of torsades de pointes arrhythmia as the first manifestation of
      congenital Long QT syndrome in a 77-year-old man with family history of sudden
      unexplained death. This case illustrates the importance of vigilant clinical
      assessment and genetic counseling in families with sudden death in order to
      identify properly asymptomatic relatives at risk for cardiac events. It also
      demonstrates that Long QT syndrome can still manifest with potentially fatal
      arrhythmias late in life in previously asymptomatic elderly patients.

PMID- 29194875
TI  - Heterologous Expression, Biosynthetic Studies, and Ecological Function of the
      Selective Gq-Signaling Inhibitor FR900359.
AB  - The cyclic depsipeptide FR900359 (FR), isolated from the tropical plant Ardisia
      crenata, is a strong and selective inhibitor of Gq proteins, making it an
      indispensable pharmacological tool to study Gq-related processes, as well as a
      promising drug candidate. Gq inhibition is a novel mode of action for defense
      chemicals and crucial for the ecological function of FR, as shown by in vivo
      experiments in mice, its affinity to insect Gq proteins, and insect toxicity
      studies. The uncultured endosymbiont of A. crenata was sequenced, revealing the
      FR nonribosomal peptide synthetase (frs) gene cluster. We here provide a detailed
      model of FR biosynthesis, supported by in vitro enzymatic and bioinformatic
      studies, and the novel analogue AC-1, which demonstrates the flexibility of the
      FR starter condensation domains. Finally, expression of the frs genes in E. coli
      led to heterologous FR production in a cultivable, bacterial host for the first
      time.

PMID- 29194877
TI  - Tachycardia with varying atrio-ventricular relationships: What is the mechanism?

PMID- 29194876
TI  - Rational decision making in medicine: Implications for overuse and underuse.
AB  - In spite of substantial spending and resource utilization, today's health care
      remains characterized by poor outcomes, largely due to overuse
      (overtesting/overtreatment) or underuse (undertesting/undertreatment) of health
      services. To a significant extent, this is a consequence of low-quality decision
      making that appears to violate various rationality criteria. Such suboptimal
      decision making is considered a leading cause of death and is responsible for
      more than 80% of health expenses. In this paper, we address the issue of overuse
      or underuse of health care interventions from the perspective of rational choice
      theory. We show that what is considered rational under one decision theory may
      not be considered rational under a different theory. We posit that the questions
      and concerns regarding both underuse and overuse have to be addressed within a
      specific theoretical framework. The applicable rationality criterion, and thus
      the "appropriateness" of health care delivery choices, depends on theory
      selection that is appropriate to specific clinical situations. We provide a
      number of illustrations showing how the choice of theoretical framework
      influences both our policy and individual decision making. We also highlight the
      practical implications of our analysis for the current efforts to measure the
      quality of care and link such measurements to the financing of health care
      services.

PMID- 29194879
TI  - Environmental heterogeneity and biotic interactions mediate climate impacts on
      tropical forest regeneration.
AB  - Predicting the fate of tropical forests under a changing climate requires
      understanding species responses to climatic variability and extremes. Seedlings
      may be particularly vulnerable to climatic stress given low stored resources and
      undeveloped roots; they also portend the potential effects of climate change on
      future forest composition. Here we use data for ca. 50,000 tropical seedlings
      representing 25 woody species to assess (i) the effects of interannual variation
      in rainfall and solar radiation between 2007 and 2016 on seedling survival over 9
      years in a subtropical forest; and (ii) how spatial heterogeneity in three
      environmental factors-soil moisture, understory light, and conspecific
      neighborhood density-modulate these responses. Community-wide seedling survival
      was not sensitive to interannual rainfall variability but interspecific variation
      in these responses was large, overwhelming the average community response. In
      contrast, community-wide responses to solar radiation were predominantly
      positive. Spatial heterogeneity in soil moisture and conspecific density were the
      predominant and most consistent drivers of seedling survival, with the majority
      of species exhibiting greater survival at low conspecific densities and positive
      or nonlinear responses to soil moisture. This environmental heterogeneity
      modulated impacts of rainfall and solar radiation. Negative conspecific effects
      were amplified during rainy years and at dry sites, whereas the positive effects
      of radiation on survival were more pronounced for seedlings existing at high
      understory light levels. These results demonstrate that environmental
      heterogeneity is not only the main driver of seedling survival in this forest but
      also plays a central role in buffering or exacerbating impacts of climate
      fluctuations on forest regeneration. Since seedlings represent a key bottleneck
      in the demographic cycle of trees, efforts to predict the long-term effects of a
      changing climate on tropical forests must take into account this environmental
      heterogeneity and how its effects on regeneration dynamics play out in long-term
      stand dynamics.

PMID- 29194878
TI  - Knowledge regarding hepatitis B mother-to-child transmission among healthcare
      workers in South China.
AB  - To determine the knowledge regarding hepatitis B virus (HBV) mother-to-child
      transmission (MTCT) and its prevention and treatment among healthcare workers
      (HCWs) in Guangdong Province, China, an HBV endemic area. An HBV knowledge
      questionnaire was administered to 900 HCWs from the 3rd Affiliated Hospital of
      Sun Yat-Sen University and 2 rural hospitals in Guangdong Province. The 27 items
      in the questionnaire fell into 3 sections: HBV MTCT general knowledge,
      respondents' practices of preventing HBV MTCT and awareness of the resources of
      preventing HBV MTCT. The data collected were coded and analysed using SPSS
      software version 20. In total, 503 of 900 HCWs responded to the survey (response
      rate: 55.9%). Eighty-four individuals responded correctly to all of the knowledge
      questions: 58 were doctors, and 26 were nurses (P < .05). Doctors more often
      performed practices than nurses (t = 3.591, P < .01). Participants from the
      infectious disease department demonstrated a significantly higher proportion of
      correct answers and resource utilization than other specialties (chi2  = 14.052,
      7.998, P < .01). In terms of the average knowledge score, t test or ANOVA showed
      that there were significant differences between the specialty groups (t = 3.110,
      P < .01), hospital level groups (t = 2.337, P < .05) and age groups (F = 3.020, P
      < .05). Respondents' initiative increased with hospital level and age (t = 2.993,
      7.493, P < .01). A considerable percentage of HCWs has misconceptions about HBV
      MTCT. Healthcare workers, in particular nurses, those working in noninfectious
      disease departments or township hospitals and younger medical staff, lack
      systematic and comprehensive knowledge about HBV MTCT and are in urgent need of
      HBV-related training.

PMID- 29194880
TI  - Zika virus dynamics in body fluids and risk of sexual transmission in a non
      endemic area.
AB  - OBJECTIVE: To understand Zika virus (ZIKV) dynamics in fluids of infected
      individuals and the risk of sexual transmission. METHODS: Prospective study at
      two centres in Spain. Patients with probable or confirmed diagnosis of ZIKV
      infection were clinically followed up, and fluid samples were collected from
      saliva, serum, urine and semen or vaginal secretion following the study protocol.
      Non-traveller-sexual partners were offered to participate. RESULTS: From January
      2016 to December 2016, we included a total of 11 traveller patients and six
      sexual contacts. Six patients were male, with a median age of 38 years (IQR 30
      45). We performed 61 RT-PCR determinations, seven of which were positive.
      Positive results were retrieved from serum, urine, semen and vaginal tract. One
      of four women tested positive for ZIKV RNA in vaginal swabs collected during the
      first 45 days after symptoms onset. Clearance occurred between day 37 and day 69
      after symptoms onset. One of five men tested positive for ZIKV RNA in semen
      collected during the first 45 days after symptoms onset. Clearance occurred
      between day 23 and 107 after symptoms onset. Six patients had sexual relations
      during the defined period. All tested patients were negative for ZIKV infection
      by serological testing. CONCLUSION: ZIKV shedding persistence in genital fluids
      occurs in a significant number of symptomatic patients after visiting an endemic
      area. We did not find any ZIKV seroconversion among the three male contacts who
      were investigated. Diagnostic algorithms may be updated to include genital tract
      fluid specimens in the diagnostic process.

PMID- 29194881
TI  - Ultrasensitive Chemiluminescent Detection of Cathepsin B: Insights into the New
      Frontier of Chemiluminescent Imaging.
AB  - Let there be light: Chemiluminescence provides a bright detection signal against
      a dark background and offers an excellent signal-to-noise ratio for analysis.
      Now, a chemiluminescent probe for cathepsin B has been developed that provides a
      16,000-fold improvement in sensitivity for detecting protease activity.

PMID- 29194882
TI  - Burchard Franck (1926-2017).

PMID- 29194883
TI  - Total Synthesis of (+)-Sarcophytin.
AB  - A total synthesis of the cembranoid (+)-sarcophytin is presented, featuring a
      Diels-Alder cycloaddition of an enone as the dienophile with an ester-derived
      dienoate. The study highlights a peculiar geometric preference for the Z dienoate
      to furnish the cycloadduct. The endgame involves a reaction cascade, including
      lactone opening, alcohol oxidation, and ketone epimerization to complete an
      efficient synthesis. A salient feature of the synthesis is the resulting
      reassignment of the absolute configuration, which corrects the previously
      reported nominal structure.

PMID- 29194884
TI  - Noncovalent Interactions of pi Systems with Sulfur: The Atomic Chameleon of
      Molecular Recognition.
AB  - The relative strength of noncovalent interactions between a thioether sulfur atom
      and various pi systems in designed top pan molecular balances was determined by
      NMR spectroscopy. Compared to its oxygen counterpart, the sulfur atom displays a
      remarkable ability to interact with almost equal facility over the entire range
      of pi systems studied, with the simple alkene emerging as the most powerful
      partner. With the exception of the O???heteroarene interaction, all noncovalent
      interactions of sulfur with pi systems are favoured over oxygen.

PMID- 29194885
TI  - Evaluating effectiveness in adolescent mental health inpatient units: A
      systematic review.
AB  - Adolescent mental health research is a developing area. Inpatient units are the
      most widely used acute element of adolescent mental health services
      internationally. Little is known about inpatient units, particularly when it
      comes to measuring improvement for adolescents. Clinical outcome measurement in
      the broad context has gathered momentum in recent years, driven by the need to
      assess services. The measurement of outcomes for adolescents who access inpatient
      care is critical, as they are particularly vulnerable and are often considered
      the most difficult to treat. Following the PRISMA guidelines, the aim of this
      review was to assess whether adolescent inpatient units are effective and
      understand how outcomes are measured. CINAHL, MEDLINE with Full Text, ERIC,
      PsycINFO, and Cochrane databases were systematically searched. Studies were
      included if the inpatient units were generic and adolescents were between the
      mean age of 12-25 years. Furthermore, studies published in English within the
      last ten years were included. Exclusions were outpatient and disorder-specific
      inpatient settings. A total of 16 studies were identified. Each study
      demonstrated effectiveness on at least one outcome measure in terms of symptom
      stabilization. However, several outcome measures were used and therefore
      inpatient units lack consistency in how they measure improvement. Inpatient units
      are effective for the majority of young people as they result in symptom
      stabilization. Whilst symptom stabilization can be achieved, future research
      examining the mechanism of change is needed.

PMID- 29194886
TI  - How I do hanging manoeuvres to facilitate portal vein resection during
      pancreaticoduodenectomy for borderline tumours.

PMID- 29194887
TI  - The pi-Tetrel Bond and its Influence on Hydrogen Bonding and Proton Transfer.
AB  - The positive region that lies above the plane of F2 TO (T=C and Si) interacts
      with malondialdehyde (MDA), which contains an intramolecular H-bond. The T atom
      of F2 TO can lie either in the MDA molecular plane, forming a T???O tetrel bond,
      or F2 TO can stack directly above MDA in a parallel arrangement. The former
      structure is more stable than the latter, and in either case, F2 SiO engages in a
      much stronger interaction than does F2 CO, reaching nearly 200 kJ mol-1 . The pi
      tetrel bond strengthens/weakens the MDA H-bond when the bond is formed to the
      hydroxyl/carbonyl group of MDA, and causes an accompanying inhibition/promotion
      of proton transfer within this H-bond; this effect is stronger for F2 SiO. These
      same aspects can be tuned by substituents placed on any of the C atoms of MDA,
      although their effects are not fully correlated with the electron-withdrawing or
      electron-releasing properties of the substituent. A new type of pi-pi tetrel bond
      occurs when the pi-hole on the T atom of F2 TO approaches the middle carbon atom
      of MDA from above, and a similar configuration is also found between F2 TO and
      benzene. Evidence for extensive C???C pi-pi tetrel bonding in crystal materials
      is presented.

PMID- 29194888
TI  - Diverged Plant Terpene Synthases Reroute the Carbocation Cyclization Path towards
      the Formation of Unprecedented 6/11/5 and 6/6/7/5 Sesterterpene Scaffolds.
AB  - Sesterterpenoids are a relatively rare class of plant terpenes. Sesterterpene
      synthase (STS)-mediated cyclization of the linear C25 isoprenoid precursor
      geranylfarnesyl diphosphate (GFPP) defines sesterterpene scaffolds. So far only a
      very limited number of STSs have been characterized. The discovery of three new
      plant STSs is reported that produce a suite of sesterterpenes with unprecedented
      6/11/5 and 6/6/7/5 fused ring systems when transiently co-expressed with a GFPP
      synthase in Nicotiana benthamiana. Structural elucidation, feeding experiments,
      and quantum chemical calculations suggest that these STSs catalyze an unusual
      cyclization path involving reprotonation, intramolecular 1,6 proton transfer, and
      concerted but asynchronous bicyclization events. The cyclization is diverted from
      those catalyzed by the characterized plant STSs by forming unified 15/5 bicyclic
      sesterterpene intermediates. Mutagenesis further revealed a conserved amino acid
      residue implicated in reprotonation.

PMID- 29194890
TI  - Ultra-late recurrence of gastrointestinal stromal tumour: case report and
      literature review.

PMID- 29194889
TI  - Spectroscopic Evidence for Ligand Substitution Reactions at the Solid-Liquid
      Interface of a Sub-micrometer Gold(I) Carbene Complex.
AB  - Colloidal coordination compounds in the sub-micrometer range were synthesized
      from a chloro gold(I) carbene complex via the anti-solvent procedure and
      stabilized by a surfactant shell of Tween 20. This compound was successfully
      applied as model system to monitor heterogeneous multiphase ligand substitution
      reactions at the solid-liquid interface.

PMID- 29194891
TI  - Utero-cutaneous fistula following Caesarean section.

PMID- 29194892
TI  - Robust Chemistry: The Importance of Data and Methods Sharing.
AB  - "... Robustness in chemistry can be enhanced by increasing the adoption of best
      data-sharing practices and the use of photos and videos for sharing methods and
      practical knowledge. Journals are an integral part of the foundation of
      scientific endeavor, and methods and data sharing are complementary practices
      that could lead to a step change in how we conduct and report research ..." Read
      more in the Editorial by Mattias Bjornmalm and Frank Caruso.

PMID- 29194893
TI  - Mesenteric cyst: an uncommon cause of acute abdomen.

PMID- 29194894
TI  - Oesophageal adenocarcinoma associated with a right-sided aortic arch.

PMID- 29194895
TI  - Circular Photoinduced Electron Transfer in a Donor-Acceptor-Acceptor Triad.
AB  - An electron-donor-acceptor-acceptor (D-A1 -A2 ) triad has been developed that
      provides the first proof-of-concept for a photoinitiated molecular circuit. After
      photoexcitation into an optical charge-transfer transition between D and A1 ,
      subsequent thermal electron-transfer from A1.- to A2 is followed by geometric
      rearrangement in the D.+ -A1 -A2.- charge-separated state to form an ion-pair
      contact. This facilitates "forward" charge recombination between A2.- and D.+ to
      complete the molecular circuit with an estimated quantum efficiency of 4 % in
      toluene at 298 K.

PMID- 29194896
TI  - Bio-inspired Photocatalytic Ruthenium Complexes: Synthesis, Optical Properties,
      and Solvatochromic Effect.
AB  - We report the synthesis, characterization, and photo-physical properties of two
      new rutheniumII -phenol-imidazole complexes. These bio-mimetic complexes have
      potential as photocatalysts for water splitting. Owing to their multiple phenol
      imidazole groups, they have a higher probability of light-induced radical
      formation than existing complexes. The newly synthesized complexes show improved
      overlap with the solar spectrum compared to other rutheniumII -phenol-imidazole
      complexes, and their measured lifetimes are suitable for light-induced radical
      formation. In addition, we conducted solvatochromic absorption measurements,
      which elegantly follow Marcus theory, and demonstrate the symmetry differences
      between the two complexes. The solvatochromic measurements further imply electron
      localization onto one of the ligands. The new complexes may find applications in
      photocatalysis, dye-sensitized solar cells, biomedicine, and sensing. Moreover,
      their multiple chelating units make them promising candidates for light-activated
      metal organic radical frameworks, i.e. metal-organic frameworks that contain
      organic radicals activated by light.

PMID- 29194897
TI  - A Six-Oxidase Cascade for Tandem C-H Bond Activation Revealed by Reconstitution
      of Bicyclomycin Biosynthesis.
AB  - As a commercial antibiotic, bicyclomycin (BCM) is currently the only known
      natural product targeting the transcription termination factor rho. It belongs to
      a family of highly functionalized diketopiperazine (DKP) alkaloids and bears a
      unique O-bridged bicyclo[4.2.2]piperazinedione ring system, a C1 triol, and
      terminal exo-methylene groups. We have identified and characterized the BCM
      biosynthetic pathway by heterologous biotransformations, in vitro biochemical
      assays, and one-pot enzymatic synthesis. A tRNA-dependent cyclodipeptide synthase
      guides the heterodimerization of leucine and isoleucine to afford the DKP
      precursor; subsequently, six redox enzymes, including five alpha
      ketoglutarate/Fe2+ -dependent dioxygenases and one cytochrome P450 monooxygenase,
      regio- and stereoselectively install four hydroxy groups (primary, secondary, and
      two tertiary), an exo-methylene moiety, and a medium-sized bridged ring through
      the functionalization of eight unactivated C-H bonds.

PMID- 29194898
TI  - Perioperative albumin ratio is associated with post-operative pancreatic fistula.
AB  - BACKGROUND: Despite improvements in surgical techniques and perioperative
      management, post-operative pancreatic fistula (POPF) remains a serious
      complication after pancreaticoduodenectomy (PD). The aim of this study was to
      evaluate the role of perioperative clinical variables of patients, including
      albumin level, in predicting pancreatic fistula. METHODS: A total of 86 patients
      underwent PD for pancreas cancer between 2011 and 2017 at our institution. We
      prospectively investigated the relation between patient's characteristics and the
      incidence of clinically relevant (CR)-POPF. Perioperative albumin ratio was
      defined as post-operative day 1 (POD1) albumin level/preoperative albumin level.
      RESULTS: A total of 23 patients (26.7%) developed CR-POPF. At univariate analysis
      POPF correlated with soft pancreas (P = 0.045), low POD1 albumin (P = 0.02), POD1
      and POD3 amylase levels in drainage fluid (P = 0.003 and P = 0.014, respectively)
      and perioperative albumin ratio (0.58 +/- 0.10 versus 0.69 +/- 0.12 in patients
      without POPF; P = 0.003). No significant correlations with POPF were demonstrated
      for surgical time, serum amylase levels and preoperative albumin levels. At
      multivariate analysis POD3 amylase level in drainage fluid and perioperative
      albumin ratio were the only significant independent parameters (P = 0.027 and P =
      0.047, respectively). CONCLUSIONS: Perioperative albumin ratio can predict POPF
      after PD.

PMID- 29194900
TI  - Jejunogastric intussusception: shall we think about it?

PMID- 29194899
TI  - Improving screening and brief intervention activities in primary health care:
      Secondary analysis of professional accuracy based on the AUDIT-C.
AB  - INTRODUCTION AND OBJECTIVE: The ODHIN trial found that training and support and
      financial reimbursement increased the proportion of patients that were screened
      and given advice for their heavy drinking in primary health care. However, the
      impact of these strategies on professional accuracy in delivering screening and
      brief advice is underresearched and is the focus of this paper. METHOD: From 120
      primary health care units (24 in each jurisdiction: Catalonia, England, the
      Netherlands, Poland, and Sweden), 746 providers participated in the baseline and
      the 12-week implementation periods. Accuracy was measured in 2 ways: correctness
      in completing and scoring the screening instrument, AUDIT-C; the proportion of
      screen-negative patients given advice, and the proportion of screen-positive
      patients not given advice. Odds ratios of accuracy were calculated for type of
      profession and for intervention group: training and support, financial
      reimbursement, and internet-based counselling. RESULTS: Thirty-two of 36 711
      questionnaires were incorrectly completed, and 65 of 29 641 screen-negative
      patients were falsely classified. At baseline, 27% of screen-negative patients
      were given advice, and 22.5% screen-positive patients were not given advice.
      These proportions halved during the 12-week implementation period, unaffected by
      training. Financial reimbursement reduced the proportion of screen-positive
      patients not given advice (OR = 0.56; 95% CI, 0.31-0.99; P < .05). CONCLUSION:
      Although the use of AUDIT-C as a screening tool was accurate, a considerable
      proportion of risky drinkers did not receive advice, which was reduced with
      financial incentives.

PMID- 29194901
TI  - Photobiocatalysis: Activating Redox Enzymes by Direct or Indirect Transfer of
      Photoinduced Electrons.
AB  - Biocatalytic transformation has received increasing attention in the green
      synthesis of chemicals because of the diversity of enzymes, their high catalytic
      activities and specificities, and mild reaction conditions. The idea of solar
      energy utilization in chemical synthesis through the combination of
      photocatalysis and biocatalysis provides an opportunity to make the "green"
      process greener. Oxidoreductases catalyze redox transformation of substrates by
      exchanging electrons at the enzyme's active site, often with the aid of electron
      mediator(s) as a counterpart. Recent progress indicates that photoinduced
      electron transfer using organic (or inorganic) photosensitizers can activate a
      wide spectrum of redox enzymes to catalyze fuel-forming reactions (e.g., H2
      evolution, CO2 reduction) and synthetically useful reductions (e.g., asymmetric
      reduction, oxygenation, hydroxylation, epoxidation, Baeyer-Villiger oxidation).
      This Review provides an overview of recent advances in light-driven activation of
      redox enzymes through direct or indirect transfer of photoinduced electrons.

PMID- 29194902
TI  - Metastatic prostate cancer incidence in Australia after amendment to prostate
      specific antigen screening guidelines.
AB  - BACKGROUND: To compare the incidence of newly diagnosed metastatic prostate
      cancer at an Australian facility pre- and post-publication of the United States
      Preventive Services Task Force (USPSTF) guidelines and subsequent amendment of
      the Royal Australian College of General Practitioners Preventive Activities in
      General Practice guidelines. METHODS: A retrospective analysis was undertaken by
      patients with newly diagnosed prostate cancer following transrectal ultrasound
      guided biopsy between 2009 and 2014. Patients were divided into two even groups
      based on whether they had undergone their transrectal ultrasound biopsy pre-
      (2009-2011) or post- (2013-2014) publication of USPSTF guidelines. Metastatic
      disease was determined by computed tomography chest, abdomen, pelvis as well as
      nuclear medicine bone scan. A comparison in the incidence of newly diagnosed
      metastatic prostate cancer was made. RESULTS: A total of 130 patients were
      allocated into each group. In the pre-USPSTF group, 23 out of 130 patients had
      newly diagnosed metastatic prostatic cancer (17.7%). In the post-USPSTF group, 41
      out of 130 (31.5%) had newly diagnosed metastatic prostate cancer (P < 0.05). The
      mean and median prostate-specific antigen was 15.9 and 9.4 (pre-guideline group)
      and 33.0 and 9.8 (post-guideline group), respectively (P = 0.02). The post
      guidelines group had a higher incidence of low-grade disease (Gleason <7), a
      decreased incidence of intermediate grade disease (Gleason 7) and a relatively
      unchanged incidence in high-risk disease (Gleason >7). CONCLUSION: The incidence
      of newly diagnosed metastatic prostate cancer nearly doubled in patients referred
      to our Urology Department post-release of the USPSTF guidelines.

PMID- 29194903
TI  - The Hydrogen Evolution Reaction in Alkaline Solution: From Theory, Single Crystal
      Models, to Practical Electrocatalysts.
AB  - The hydrogen evolution reaction (HER) is a fundamental process in
      electrocatalysis and plays an important role in energy conversion for the
      development of hydrogen-based energy sources. However, the considerably slow rate
      of the HER in alkaline conditions has hindered advances in water splitting
      techniques for high-purity hydrogen production. Differing from well documented
      acidic HER, the mechanistic aspects of alkaline HER are yet to be settled. A
      critical appraisal of alkaline HER electrocatalysis is presented, with a special
      emphasis on the connection between fundamental surface electrochemistry on single
      crystal models and the derived molecular design principle for real-world
      electrocatalysts. By presenting some typical examples across theoretical
      calculations, surface characterization, and electrochemical experiments, we try
      to address some key ongoing debates to deliver a better understanding of alkaline
      HER at the atomic level.

PMID- 29194904
TI  - Investigating the Conformation of the Bridged Monosaccharide Levoglucosan.
AB  - Levoglucosan is one of the main products of the thermal degradation of glucose
      and cellulose and is commonly used as a tracer for biomass burning. Herein we
      report a conformational analysis of levoglucosan under isolation conditions, by
      means of microwave spectroscopy coupled with ultrafast laser vaporization in
      supersonic expansions. We observed three different conformations of levoglucosan
      in the gas phase. They all share a common heavy atom rigid bicyclic structure.
      The difference between the three of them lies in the network of intramolecular
      hydrogen bonds that arises from the OH groups at positions 2, 3 and 4. The
      different combinations of H-bonds give richness to the conformational landscape
      of levoglucosan. The gas phase conformers obtained in this work are compared to
      the crystal structure of levoglucosan previously reported. Although the heavy
      atom frame remains unchanged, there are significant differences in the positions
      of the H-atoms. In addition, the levoglucosan structure can be compared to the
      related glucose, for which gas phase conformational studies exist in the
      literature. In this case, in going from glucose to levoglucosan, there is an
      inversion in the chair conformation of the pyranose ring. This forces the OH
      groups to adopt axial positions (instead of the more favorable equatorial
      positions in glucose) and completely changes the pattern of intramolecular H
      bonds.

PMID- 29194905
TI  - Mental health nurses and mental health peer workers: Self-perceptions of role
      related clinical competences.
AB  - In a mental healthcare that embraces a recovery-oriented practice, the employment
      of mental health peer workers is encouraged. Although peer workers are
      increasingly working together with nurses, there is a lack of research that
      explores how nurses and peer workers perceive their role-related competences in
      clinical practice. The aim of this study was to clarify and understand these self
      perceptions in order to identify the specificity and potential complementarity of
      both roles. This insight is needed to underpin a successful partnership between
      both vocations. A qualitative descriptive research design based on principles of
      critical incident methodology was used. Twelve nurses and eight peer workers from
      different mental healthcare organizations participated. A total of 132 reported
      cases were analysed. Rigour was achieved through thick description, audit trail,
      investigator triangulation and peer review. Nurses relate their role-related
      competences predominantly with being compliant with instructions, being a team
      player and ensuring security and control. Peer workers relate their role-related
      competences with being able to maintain themselves as a peer worker, building up
      a relationship that is supportive for both the patient and themselves, and to
      utilize their lived experience. Both nurses and peer workers assign a major role
      to the team in determining their satisfaction with their competences.
      Consequently, what is perceived as important for the team appears to overshadow
      their self-assessment of competences. The findings highlighted the importance of
      paying more attention to identity construction, empowerment and role competence
      development of nurses and peer workers in their respective education and ongoing
      training.

PMID- 29194906
TI  - Radical gastric cancer surgery results in widespread upregulation of pro
      tumourigenic intraperitoneal cytokines.
AB  - BACKGROUND: Radical surgical resection is the mainstay of curative treatment for
      oesophagogastric malignancy. However, survival and recurrence rates remain poor.
      Theoretical data suggests that the inflammatory response to surgery can promote
      tumour recurrence. The local and systemic inflammatory response to radical
      oesophagogastric cancer surgery has not been fully characterized. We aimed to
      measure this response, particularly factors associated with tumour implantation.
      METHODS: Consecutive patients undergoing radical junctional or gastric cancer
      resection over 12 months were recruited. Repeated serum and adipose tissue were
      collected intra-operatively. Adipose tissue was collected adjacent and remote to
      the tumour, and cytokine messenger RNA (mRNA) expression was measured. Post
      operatively, daily serum was collected for 7 days, and analysed for inflammatory
      cell profile and cytokine concentration. RESULTS: There were nine patients
      recruited (67.1 +/- 2.1 years). mRNA expression of interleukin-6 (IL-6), CC
      chemokine ligand-2 and IL-1beta increased in adipose tissue intra-operatively (P
      < 0.05), equally both adjacent and remote from the tumour site. Serum IL-6
      concentration increased from 23.3 pg/mL to 161.8 pg/mL intra-operatively (P <
      0.05) before falling steadily to 35.7 pg/mL post-operatively (P < 0.05). Serum
      tumour necrosis factor-alpha was elevated throughout, and IL-1beta levels were
      unaffected. Leukocyte and neutrophil populations increased, while T-cell and
      dendritic cell populations decreased intra-operatively (P < 0.05). CONCLUSION:
      Radical surgery dramatically upregulates the expression of pro-tumourigenic
      cytokines in the peritoneum. There is also a marked systemic immune and
      inflammatory response to surgery, including downregulation of T-cell and
      dendritic cell populations. This offers two potential pathways that may
      facilitate tumour progression - local inflammation promoting peritoneal adherence
      and implantation, and secondary suppression of immunosurveillance due to
      circulating inflammatory response.

PMID- 29194908
TI  - Artificial beta-Double Helices from Achiral gamma-Peptides.
AB  - Double helices are not common in polypeptides and proteins except in the peptide
      antibiotic gramicidin A and analogous l,d-peptides. In contrast to natural
      polypeptides, remarkable beta-double-helical structures from achiral gamma
      peptides built from alpha,beta-unsaturated gamma-amino acids have been observed.
      The crystal structures suggest that they adopted parallel beta-double helical
      structures and these structures are stabilized by the interstrand backbone amide
      H-bonds. Furthermore, both NMR spectroscopy and fluorescence studies support the
      existence of double-helical conformations in solution. Although a variety of
      folded architectures featuring distinct H-bonds have been discovered from the
      beta- and gamma-peptide foldamers, this is the first report to show that achiral
      gamma-peptides can spontaneously intertwine into beta-double helical structures.

PMID- 29194907
TI  - 100 Days of marine Synechococcus-Ruegeria pomeroyi interaction: A detailed
      analysis of the exoproteome.
AB  - Marine phototroph and heterotroph interactions are vital in maintaining the
      nutrient balance in the oceans as essential nutrients need to be rapidly cycled
      before sinking to aphotic layers. The aim of this study was to highlight the
      molecular mechanisms that drive these interactions. For this, we generated a
      detailed exoproteomic time-course analysis of a 100-day co-culture between the
      model marine picocyanobacterium Synechococcus sp. WH7803 and the Roseobacter
      strain Ruegeria pomeroyi DSS-3, both in nutrient-enriched and natural
      oligotrophic seawater. The proteomic data showed a transition between the initial
      growth phase and stable-state phase that, in the case of the heterotroph, was
      caused by a switch in motility attributed to organic matter availability. The
      phototroph adapted to seawater oligotrophy by reducing its selective leakiness,
      increasing the acquisition of essential nutrients and secreting conserved
      proteins of unknown function. We also report a surprisingly high abundance of
      extracellular superoxide dismutase produced by Synechococcus and a dynamic
      secretion of potential hydrolytic enzyme candidates used by the heterotroph to
      cleave organic groups and hydrolase polymeric organic matter produced by the
      cyanobacterium. The time course dataset we present here will become a reference
      for understanding the molecular processes underpinning marine phototroph
      heterotroph interactions.

PMID- 29194909
TI  - Dominant forest tree mycorrhizal type mediates understory plant invasions.
AB  - Forest mycorrhizal type mediates nutrient dynamics, which in turn can influence
      forest community structure and processes. Using forest inventory data, we
      explored how dominant forest tree mycorrhizal type affects understory plant
      invasions with consideration of forest structure and soil properties. We found
      that arbuscular mycorrhizal (AM) dominant forests, which are characterised by
      thin forest floors and low soil C : N ratio, were invaded to a greater extent by
      non-native invasive species than ectomycorrhizal (ECM) dominant forests.
      Understory native species cover and richness had no strong associations with AM
      tree dominance. We also found no difference in the mycorrhizal type composition
      of understory invaders between AM and ECM dominant forests. Our results indicate
      that dominant forest tree mycorrhizal type is closely linked with understory
      invasions. The increased invader abundance in AM dominant forests can further
      facilitate nutrient cycling, leading to the alteration of ecosystem structure and
      functions.

PMID- 29194910
TI  - Moniliophthora roreri, causal agent of cacao frosty pod rot.
AB  - : Taxonomy: Moniliophthora roreri (Cif.) H.C. Evans et al. ; Phylum
      Basidiomycota; Class Agaricomycetes; Order Agaricales; Family Marasmiaceae; Genus
      Moniliophthora. Biology: Moniliophthora roreri attacks Theobroma and Herrania
      species causing frosty pod rot. Theobroma cacao (cacao) is the host of major
      economic concern. Moniliophthora roreri is a hemibiotroph with a long biotrophic
      phase (45-90 days). Spore masses, of apparent asexual origin, are produced on the
      pod surface after initiation of the necrotrophic phase. Spores are spread by
      wind, rain and human activity. Symptoms of the biotrophic phase can include
      necrotic flecks and, in some cases, pod malformation, but pods otherwise remain
      asymptomatic. Relationship to Moniliophthora perniciosa: Moniliophthora roreri
      and Moniliophthora perniciosa, causal agent of witches' broom disease of cacao,
      are closely related. Their genomes are similar, including many of the genes they
      carry which are considered to be important in the disease process. Moniliophthora
      perniciosa, also a hemibiotroph, has a typical basidiomycete lifestyle and
      morphology, forming clamp connections and producing mushrooms. Basidiospores
      infect meristematic tissues including flower cushions, stem tips and pods.
      Moniliophthora roreri does not form clamp connections or mushrooms and infects
      pods only. Both pathogens are limited to the Western Hemisphere and are a threat
      to cacao production around the world. Agronomic importance: Disease losses caused
      by frosty pod rot can reach 90% and result in field abandonment. Moniliophthora
      roreri remains in the invasive phase in the Western Hemisphere, not having
      reached Brazil, some islands within the Caribbean and a few specific regions
      within otherwise invaded countries. DISEASE MANAGEMENT: The disease can be
      managed by a combination of cultural (for example, maintenance of tree height and
      removal of infected pods) and chemical methods. These methods benefit from
      regional application, but can be cost prohibitive. Breeding for disease
      resistance offers the greatest potential for frosty pod rot management and new
      tolerant materials are becoming available.

PMID- 29194911
TI  - Solubility-Parameter-Guided Solvent Selection to Initiate Ostwald Ripening for
      Interior Space-Tunable Structures with Architecture-Dependent Electrochemical
      Performance.
AB  - Despite significant advancement in preparing various hollow structures by Ostwald
      ripening, one common problem is the intractable uncontrollability of initiating
      Ostwald ripening due to the complexity of the reaction processes. Here, a new
      strategy on Hansen solubility parameter (HSP)-guided solvent selection to
      initiate Ostwald ripening is proposed. Based on this comprehensive principle for
      solvent optimization, N,N-dimethylformamide (DMF) was screened out, achieving
      accurate synthesis of interior space-tunable MoSe2 spherical structures (solid,
      core-shell, yolk-shell and hollow spheres). The resultant MoSe2 structures
      exhibit architecture-dependent electrochemical performances towards hydrogen
      evolution reaction and sodium-ion batteries. This pre-solvent selection strategy
      can effectively provide researchers great possibility in efficiently synthesizing
      various hollow structures. This work paves a new pathway for deeply understanding
      Ostwald ripening.

PMID- 29194912
TI  - Sharing of prescription analgesics amongst patients in family practice: Frequency
      and associated factors.
AB  - OBJECTIVE: To analyse the frequency of nonrecreational prescription analgesic
      sharing, associated factors and differences between lenders and borrowers.
      METHODS: A cross-sectional study was conducted in 10 outpatient family medicine
      practices in Croatia amongst 1000 patients to whom their physicians have
      prescribed analgesics at least once in their lives. A questionnaire was used to
      collect data about patients' pain intensity, prescription analgesic sharing
      habits, factors associated with this behaviour, perception of risks associated
      with the conduct and demographic data. Logistic regression was conducted to
      analyse independent factors associated with lending and borrowing prescription
      analgesics. RESULTS: We found that 61% of patients in family medicine practices
      engage in sharing prescription analgesics, whether it was lending (42%) and/or
      borrowing (54%). Independent predictors of lending prescription analgesics were
      as follows: history of sharing prescription medication other than analgesics,
      providing information regarding the medication alongside the prescription
      medication itself, not reading package insert that accompanies medication,
      subjective perception of personal health and decreased awareness of personal harm
      associated with prescription analgesic sharing. Independent predictors of
      prescription analgesic borrowing were as follows: younger age, communicating
      details regarding the medication that was given, scanning of package insert
      accompanying the medication, biased subjective perception of personal health and
      perceiving alternative medicine as a safer option over conventional medicine.
      CONCLUSIONS: Sharing prescription analgesics is highly prevalent amongst patients
      in family medicine. Healthcare providers should remain alert by routinely
      questioning patients regarding such behaviours. Preventive interventions should
      be conceived and established. SIGNIFICANCE: Sharing of prescription analgesics is
      a highly prevalent behaviour amongst pain patients, and there exist independent
      factors associated with such conduct. This information can be useful in the
      design of interventions aimed at mitigating analgesic sharing behaviour in the
      future.

PMID- 29194913
TI  - Regulation of Nod factor biosynthesis by alternative NodD proteins at distinct
      stages of symbiosis provides additional compatibility scrutiny.
AB  - The Lotus japonicus symbiont Mesorhizobium loti R7A encodes two copies of nodD
      and here we identify striking differences in Nod factor biosynthesis gene
      induction by NodD1 and NodD2 both in vitro and in planta. We demonstrate that
      induction of Nod factor biosynthesis genes is preferentially controlled by NodD1
      and NodD2 at specific stages of symbiotic infection. NodD2 is primarily
      responsible for induction in the rhizosphere and within nodules, while NodD1 is
      primarily responsible for induction within root hair infection threads. nodD1 and
      nodD2 mutants showed significant symbiotic phenotypes and competition studies
      establish that nodD1 and nodD2 mutants were severely outcompeted by wild-type
      R7A, indicating that both proteins are required for proficient symbiotic
      infection. These results suggest preferential activation of NodD1 and NodD2 by
      different inducing compounds produced at defined stages of symbiotic infection.
      We identified Lotus chalcone isomerase CHI4 as a root hair induced candidate
      involved in the biosynthesis of an inducer compound that may be preferentially
      recognized by NodD1 within root hair infection threads. We propose an alternative
      explanation for the function of multiple copies of nodD that provides the host
      plant with another level of compatibility scrutiny at the stage of infection
      thread development.

PMID- 29194915
TI  - Factors influencing lymph node skip metastasis in colorectal cancer: a
      retrospective study.
AB  - BACKGROUND: The risk factors for lymph node skip metastasis (LNSM) have not been
      thoroughly clarified in patients with advanced colorectal cancer (CRC). This
      study aimed to identify the risk factors for LNSM in CRC patients who underwent
      laparoscopic radical resection with D3 lymphadenectomy. METHODS: This
      retrospective cohort study included a total of 167 consecutive patients who
      underwent laparoscopic radical resection with D3 lymphadenectomy for CRC between
      April 2005 and June 2017. The patients were sorted into the LNSM-positive (skip+
      group) and LNSM-negative (skip- group) groups. Logistic regression was used to
      identify the risk factors for LNSM. RESULTS: Compared with the skip- group, the
      frequency of tumour size <5 cm, pT1-2 stage, and pN1 stage were significantly
      higher in the skip+ group (tumour size <5 cm: 68.8 versus 46.7%, P = 0.025; pT1-2
      stage: 18.8 versus 4.4%, P = 0.012; pN1 stage: 78.1 versus 57.0%, P = 0.028),
      respectively. Multivariate logistic regression analysis revealed that pT1-2 stage
      (odds ratio (OR) = 4.3, 95% confidence interval (CI): 1.1-16.6, P = 0.034) and
      pN1 stage (OR = 2.6, 95% CI: 1.1-6.8, P = 0.047) were independent risk factors
      for LNSM. CONCLUSIONS: pT1-2 stage and pN1 stage are significantly associated
      with LNSM. Radical D3 lymphadenectomy should remain standard practice for CRC.

PMID- 29194914
TI  - Cell-cell recognition and social networking in bacteria.
AB  - The ability to recognize self and to recognize partnering cells allows
      microorganisms to build social networks that perform functions beyond the
      capabilities of the individual. In bacteria, recognition typically involves
      genetic determinants that provide cell surface receptors or diffusible signalling
      chemicals to identify proximal cells at the molecular level that can participate
      in cooperative processes. Social networks also rely on discriminating mechanisms
      to exclude competing cells from joining and exploiting their groups. In addition
      to their appropriate genotypes, cell-cell recognition also requires compatible
      phenotypes, which vary according to environmental cues or exposures as well as
      stochastic processes that lead to heterogeneity and potential disharmony in the
      population. Understanding how bacteria identify their social partners and how
      they synchronize their behaviours to conduct multicellular functions is an
      expanding field of research. Here, we review recent progress in the field and
      contrast the various strategies used in recognition and behavioural networking.

PMID- 29194917
TI  - Treatment of clozapine-associated obesity and diabetes with exenatide in adults
      with schizophrenia: A randomized controlled trial (CODEX).
AB  - Clozapine causes obesity and type 2 diabetes (T2DM). Glucagon-like peptide-1 (GLP
      1) receptor agonists (e.g. exenatide) can counter clozapine-associated GLP-1
      dysregulation in animals, and may be beneficial in people on clozapine. This
      randomized, controlled, open-label, pilot trial evaluated weekly exenatide for
      weight loss among clozapine-treated obese adults with schizophrenia, with or
      without T2DM. A total of 28 outpatients were randomized to once-weekly extended
      release subcutaneous exenatide or usual care for 24 weeks. The primary outcome
      was proportion of participants with >5% weight loss. All 28 participants
      completed the study; 3/14 in the exenatide group and 2/14 in the usual care group
      had T2DM. Six people on exenatide achieved >5% weight loss vs one receiving usual
      care (P = .029). Compared with usual care, participants on exenatide had greater
      mean weight loss (-5.29 vs -1.12 kg; P = .015) and body mass index reduction (
      1.78 vs -0.39 kg/m2 ; P = .019), and reduced fasting glucose (-0.34 vs 0.39
      mmol/L; P = .036) and glycated haemoglobin levels (-0.21% vs 0.03%; P = .004).
      There were no significant differences in other metabolic syndrome components.
      Exenatide may be a promising therapeutic agent for glycaemic control and weight
      loss in clozapine-treated people with obesity, and could assist in reducing
      clozapine-associated cardio-metabolic morbidity and mortality.

PMID- 29194916
TI  - The impact of obesity in cirrhotic patients with septic shock: A retrospective
      cohort study.
AB  - BACKGROUND & AIMS: The prevalence of obesity in cirrhosis is rising. The impact
      of obesity in critically ill cirrhotic patients with sepsis/septic shock has not
      been evaluated. This study aimed to examine the relationship between obesity and
      mortality in cirrhotic patients admitted to the intensive care unit with septic
      shock. METHODS: A retrospective cohort study of all cirrhotic patients with
      septic shock (n = 362) and a recorded body mass index (BMI) from an
      international, multicentre (CATSS) database (1996-2015) was performed. Patients
      were classified by BMI as per WHO categories. Primary outcome was in-hospital
      mortality. Multivariate logistic regression analyses were carried out to
      determine independent associations with outcome. RESULTS: In this analysis, mean
      age was 56.4 years, and 62% were male. Median BMI was 26.3%, and 57.7% were
      overweight/obese. In-hospital mortality was 71%. Obese patients were more likely
      to have comorbidities of cardiac disease, lung disease and diabetes. Compared to
      survivors (n = 105), non-survivors (n = 257) had significantly higher MELD and
      APACHEII scores and higher requirements for renal replacement therapy and
      mechanical ventilation (P < .03 for all). Using multivariable logistic
      regression, increase in BMI (OR 1.07, P = .034), time delay to appropriate
      antimicrobials (OR 1.16 per hour, P = .003), APACHEII (OR 1.12 per unit, P =
      .008) and peak lactate (OR 1.15, P = .028) were independently associated with in
      hospital mortality. CONCLUSIONS: Septic shock in cirrhosis carries a high
      mortality. Increased BMI is common in critically ill cirrhotic patients and
      independently associated with increased in-hospital mortality.

PMID- 29194918
TI  - Using connectivity to identify climatic drivers of local adaptation.
AB  - Understanding the climatic drivers of local adaptation is vital. Such knowledge
      is not only of theoretical interest but is critical to inform management actions
      under climate change, such as assisted translocation and targeted gene flow.
      Unfortunately, there are a vast number of potential trait-environment
      combinations, and simple relationships between trait and environment are
      ambiguous: representing either plastic or evolved variation. Here, we show that
      by incorporating connectivity as an index of gene flow, we can differentiate
      trait-environment relationships reflecting genetic variation vs. phenotypic
      plasticity. In this way, we rapidly shorten the list of trait-environment
      combinations that are of significance. Our analysis of an existing data set on
      geographic variation in a tropical lizard shows that we can effectively rank
      climatic variables by the strength of their role in local adaptation. The promise
      of our method is a rapid and general approach to identifying the environmental
      drivers of local adaptation.

PMID- 29194920
TI  - para-Xylene Ultra-selective Zeolite MFI Membranes Fabricated from Nanosheet
      Monolayers at the Air-Water Interface.
AB  - The control of membrane morphology and microstructure is crucial to improve the
      separation performance of molecular-sieve membranes. This can be enabled by
      making thin, dense, and uniform seed-crystal coatings, which are then intergrown
      into continuous membranes. Herein, we show a novel and simple floating particle
      coating method can give closely packed monolayers of zeolite nanosheets on
      nonporous or porous supports. The zeolite nanosheet monolayer is formed at the
      air-water interface in a conical Teflon trough. As the water in the trough is
      drained, the monolayer is deposited on a support placed below. Membranes prepared
      by gel-free secondary growth of the nanosheets deposited by this method show
      unprecedented ultra-selective performance for separation of para- from ortho
      xylene (separation factor >10 000).

PMID- 29194919
TI  - A novel Chromatiales bacterium is a potential sulfide oxidizer in multiple orders
      of marine sponges.
AB  - Sponges are benthic filter feeders that play pivotal roles in coupling benthic
      pelagic processes in the oceans that involve transformation of dissolved and
      particulate organic carbon and nitrogen into biomass. While the contribution of
      sponge holobionts to the nitrogen cycle has been recognized in past years, their
      importance in the sulfur cycle, both oceanic and physiological, has only recently
      gained attention. Sponges in general, and Theonella swinhoei in particular,
      harbour a multitude of associated microorganisms that could affect sulfur cycling
      within the holobiont. We reconstructed the genome of a Chromatiales (class
      Gammaproteobacteria) bacterium from a metagenomic sequence dataset of a T.
      swinhoei-associated microbial community. This relatively abundant bacterium has
      the metabolic capability to oxidize sulfide yet displays reduced metabolic
      potential suggestive of its lifestyle as an obligatory symbiont. This bacterium
      was detected in multiple sponge orders, according to similarities in key genes
      such as 16S rRNA and polyketide synthase genes. Due to its sulfide oxidation
      metabolism and occurrence in many members of the Porifera phylum, we suggest
      naming the newly described taxon Candidatus Porisulfidus.

PMID- 29194921
TI  - Causal beliefs in people experiencing psychosis: The relationship to treatment
      accessed and the perceived helpfulness of treatment.
AB  - PURPOSE: Research suggests that the way an individual understands a health
      difficulty can influence their subsequent behaviour. The aim of this study was to
      explore the psychometric properties of a new causal belief questionnaire for
      people who have experience of psychosis. We also planned to provide an overview
      of current causal beliefs within this group and to explore the relationship
      between these beliefs and the perceived helpfulness of treatment and the
      treatment accessed. METHODS: Three hundred and eleven service-users with
      experience of psychosis completed a questionnaire designed to explore how they
      understand the cause of their difficulties. Additional information was collected
      about different aspects of treatment. RESULTS: The results of the exploratory
      factor analysis indicated a two-factor solution comprising a psychosocial and
      biogenetic scale. Individuals in this study endorsed a variety of different
      causes, with an overall preference for psychosocial explanations. No
      relationships were established between beliefs and perceptions about the
      helpfulness of treatment. Individuals who had accessed cognitive behavioural
      therapy were more likely to endorse the psychosocial factor. CONCLUSIONS:
      Individuals with psychosis consider a number of factors to be important in
      relation to the development of their experiences. These beliefs should be
      explored as part of the therapeutic process as this appears to be important to
      the individual and could potentially help inform treatment decisions.
      PRACTITIONER POINTS: The causal belief questionnaire captured two underlying
      constructs relating to psychosocial and biogenetic causes. Individuals within
      this group endorsed a range of factors; however, they prefer psychosocial causes
      overall. There was an indication that some aspects of an individual's beliefs
      were associated with the treatment they accessed.

PMID- 29194922
TI  - Material properties determining the insecticidal activity of highly divided
      porous materials on the pharaoh ant (Monomorium pharaonis).
AB  - BACKGROUND: Historically, inert insecticidal powders such as diatomaceous earth
      were researched for pest management applications, and it was revealed that these
      types of powders killed insects by desiccation. However, data on the critical
      material properties that affect their efficacy are sparse. The present study
      investigated the insecticidal effect of powdered materials on the pharaoh ant, a
      notorious domestic pest. RESULTS: The insecticidal activity of 24 porous
      materials was tested. Eight of these materials performed better than the
      benchmark, diatomaceous earth. Zeolite Y and carbon black II performed best,
      inducing 50% mortality within 40 and 55 minutes, respectively. Statistical
      analysis of seven material properties revealed that macroporous surface area and
      Brunauer-Emmett-Teller (BET) specific surface area were most predictive of
      insecticidal activity. For zeolites and ordered mesoporous silica materials, the
      most important parameters were, respectively, BET and large mesopore surface
      area. Finally, gas chromatography-mass spectrometry (GC-MS) analysis confirmed
      the adsorption of epicuticular hydrocarbons onto the zeolite powders. CONCLUSION:
      This study shows clear potential for the use of environmentally friendly, inert
      porous materials as insecticides against the pharaoh ant and identified the key
      material properties influencing insecticidal activity. The GC-MS data support the
      hypothesis that the mortality was caused by the removal of the protective
      epicuticular hydrocarbons. (c) 2017 Society of Chemical Industry.

PMID- 29194923
TI  - Tracking active groundwater microbes with D2 O labelling to understand their
      ecosystem function.
AB  - Microbial activity is key in understanding the contribution of microbial
      communities to ecosystem functions. Metabolic labelling with heavy water (D2 O)
      leads to the formation of carbon-deuterium bonds in active microorganisms. We
      illustrated how D2 O labelling allows monitoring of metabolic activity combined
      with a functional characterization of active populations in complex microbial
      communities. First, we demonstrated by single cell Raman microspectroscopy that
      all measured bacterial cells from groundwater isolates growing in complex medium
      with D2 O were labelled. Next, we conducted a labelling approach with the total
      groundwater microbiome in D2 O amended microcosms. Deuterium was incorporated in
      most measured cells, indicating metabolic activity in the oligotrophic
      groundwater. Moreover, we spiked the groundwater microbiome with organic model
      compounds. We discovered that heterotrophs assimilating veratric acid, a lignin
      derivative, showed higher labelling than heterotrophs assimilating methylamine, a
      degradation product of biomass. This difference can be explained by dilution of
      the deuterium through hydrogen from the organic compounds. Metaproteomics
      identified Sphingomonadaceae and Microbacteriaceae as key players in veratric
      acid degradation, and the metabolic pathways employed. Methylamine, in contrast,
      stimulated various proteobacterial genera. We propose this combined approach of
      Raman microspectroscopy and metaproteomics for elucidating the complex metabolic
      response of microbial populations to different stimuli.

PMID- 29194924
TI  - Microleakage around zirconia crown margins after ultrasonic scaling with self
      adhesive resin or resin modified glass ionomer cement.
AB  - OBJECTIVES: To measure microleakage around zirconia crown margins cemented with
      self-adhesive resin or resin modified glass ionomer (RMGI) cement after
      ultrasonic scaling. METHODS: 16 molars were prepared for crowns (margin 0.5 mm
      coronal of cementum-enamel junction). Preparations were digitally scanned and
      zirconia crowns milled. Specimens were divided into two groups (n = 8): self
      adhesive resin (RelyX Unicem 2) or resin modified glass ionomer (RMGI) (RelyX
      Luting Plus) cements. After cementation, specimens were ultrasonic scaled with a
      piezoelectric device (60 s, hand pressure). After thermocycling (20,000 cycles/5
      55 degrees C), specimens were immersed in 5 wt% fuchsine dye before sectioning
      bucco-lingually. Microleakage was examined under 40* light magnification.
      Statistical comparisons were made using a paired t test and a two-sample t test
      (alpha = .05). RESULTS: Ultrasonic scaling did not alter microleakage at the
      margins of crowns (P = .31). There was no significant difference in microleakage
      of scaled and untreated margins with the use of different cements (P = .21). The
      amount of microleakage around margins that were scaled was not significantly
      different between cements (P = .14). Untreated margins of crowns cemented with
      RelyX Luting Plus showed a significantly higher microleakage than those cemented
      with RelyX Unicem 2 (P = .005). CONCLUSIONS: Piezoelectric ultrasonic scaling did
      not increase microleakage at the margin of zirconia crowns cemented with self
      adhesive resin or RMGI cements. CLINICAL SIGNIFICANCE: Piezoelectric ultrasonic
      scaling around zirconia crowns did not impact marginal microleakage cemented with
      self-adhesive resin or RMGI cements.

PMID- 29194925
TI  - Heart Rate Variability and Sensitivity to Experimentally Induced Pain: A
      Replication.

PMID- 29194926
TI  - Survivors of Child Maltreatment and Postpartum Depression: An Integrative Review.
AB  - INTRODUCTION: An integrative review was performed to explore the relationship
      between a maternal history of child maltreatment and subsequent postpartum
      depression (PPD) symptoms. METHODS: Six electronic databases were used to explore
      the literature, including PubMed, CINAHL, MEDLINE, PsycINFO, Embase, and Scopus.
      Studies were included that used victims of child maltreatment as one of the
      independent variables and PPD symptoms as one of the dependent variables. Studies
      were excluded if they focused only on women with adult intimate partner violence
      or women with PPD who were perpetrators of child abuse rather than survivors. The
      studies were required to be original research, and there was no limit to years or
      language. The search yielded 589 studies, 16 of which were included in the final
      sample. These studies were assessed for quality, and a data display matrix was
      developed to extract the sample, design, methods, operational definitions for
      independent and dependent variables of interest, major findings with effect
      sizes, and limitations. Using the data display matrix, the studies' methods and
      findings were synthesized for divergent and convergent patterns. RESULTS: Studies
      were varied in their designs, samples, and operational definitions of child
      maltreatment and PPD, and were low to moderate in quality. Results were
      inconsistent, but a majority suggest a positive association between a maternal
      history of child maltreatment and subsequent symptoms of PPD. DISCUSSION: Child
      maltreatment and PPD are complex issues that require careful screening by women's
      health care providers and clearly defined operational definitions in future
      research. Implications for clinical practice and research are discussed.

PMID- 29194927
TI  - Computer guided sinus floor elevation through lateral window approach with
      simultaneous implant placement.
AB  - BACKGROUND: The introduction of CAD/CAM technology in implant dentistry has
      marked a new era, allowing various procedures to be carried out with a level of
      great precision and accuracy. PURPOSE: The aim of the present study is to compare
      the efficacy of a CAD/CAM generated surgical cutting guide in the reduction of
      incidence of membrane perforation during maxillary sinus floor elevation in
      relation to the standard lateral window approach technique. MATERIALS AND
      METHODS: Twenty cases of maxillary sinus elevation were randomly divided into 2
      groups. The first group received computer guided sinus floor elevation through
      lateral window approach and simultaneous implant placement while the second group
      received standard sinus elevation procedure through lateral window approach with
      simultaneous implant placement. RESULTS: In the computer guided group, 3 out of
      10 cases presented with sinus septa, only 1 case suffered from membrane
      perforation during the elevation process. In the non-guided group, 3 cases
      suffered from membrane perforation, 2 of which were complicated by sinus septa.
      CONCLUSION: Within the limits of this study, computer guided sinus floor
      elevation showed promising results in accurately modifying the lateral window
      osteotomy and presents as a safe alternative to the standard technique.

PMID- 29194928
TI  - Clinical pathway improves implementation of evidence-based strategies for the
      management of androgen deprivation therapy-induced side effects in men with
      prostate cancer.
AB  - OBJECTIVES: To assess the effects of a prostate cancer (PCa) clinical pathway on
      the implementation of evidence-based strategies for the management of androgen
      deprivation therapy (ADT)-induced side effects. PATIENTS AND METHODS: A clinical
      pathway was introduced at hospital level in 2015. The pathway consists of
      evidence-based strategies for the management of ADT-induced side effects. All
      patients with PCa receiving ADT for >6 months were eligible to enter the clinical
      pathway. Data on recommended evidence-based strategies were retrospectively
      extracted from the electronic health records of all eligible patients in the year
      before (2014) and the year of implementation of the pathway (2015). Descriptive
      statistics were used for patient characteristics. The chi-squared test (or
      Fisher's exact test) and Mann-Whitney U-test were used to compare results in the
      control group with those in the intervention group. RESULTS: In total, 126
      patients were included in the control group and 132 patients in the intervention
      group. Baseline patient characteristics were well balanced. After implementation
      of the pathway, metabolic, bone and cardiac risk assessment screenings were more
      frequently applied in the intervention group (metabolic 46% vs 4%; bone 58% vs
      10%; cardiac 61% vs 16%; P < 0.001). Advice on strategies preventing ADT-induced
      side effects was more frequently provided in the intervention group (exercise 62%
      vs 11%; nutrition 58% vs 10%; psycho-education 54% vs 13%; P < 0.001).
      CONCLUSION: A clinical pathway for patients with PCa improved the implementation
      of evidence-based strategies for the management of ADT-induced side effects. A
      clinical pathway could serve as a method to bridge the gap between evidence-based
      guidelines and daily clinical practice.

PMID- 29194929
TI  - Procarboxypeptidase U (proCPU, TAFI, proCPB2) in cerebrospinal fluid during
      ischemic stroke is associated with stroke progression, outcome and blood-brain
      barrier dysfunction.
AB  - : Essentials Little is known of procarboxypeptidase U (proCPU) in cerebrospinal
      fluid (CSF) of stroke patients. ProCPU levels were studied in CSF of controls and
      non-thrombolyzed acute ischemic stroke patients. ProCPU is elevated in CSF of
      stroke patients compared with controls. ProCPU in CSF correlates with stroke
      progression, outcome, and blood-brain barrier dysfunction. SUMMARY: Background
      Procarboxypeptidase U (proCPU, TAFI, proCPB2), the zymogen of CPU, which is a
      potent antifibrinolytic enzyme and a modulator of inflammation, has previously
      been investigated in plasma of stroke patients, but so far, no information on the
      proCPU levels in cerebrospinal fluid (CSF) during acute ischemic stroke (AIS) is
      available. Objectives This case-control observational study investigates proCPU
      in CSF of AIS patients compared with controls with an intact blood-brain barrier
      (BBB) and evaluates the relationship of CSF/plasma proCPU ratios with stroke
      parameters. Methods A sensitive HPLC-based enzymatic assay was used to determine
      proCPU levels in CSF of non-thrombolyzed patients in the hyperacute phase (< 24 h
      after onset) of AIS (n = 72). Individuals (n = 32) without stroke, an intact BBB
      and no apparent abnormalities in biochemical and microbiological tests, served as
      controls. Relations between the CSF/plasma proCPU ratio and (i) stroke severity,
      (ii) stroke progression/recurrence, (iii) stroke outcome and (iv) BBB dysfunction
      (CSF/serum albumin ratio) were assessed. Results Mean (SEM) proCPU levels were
      elevated in the CSF of stroke patients compared with controls (4.36 (0.23) U L-1
      vs. 3.50 (0.23) U L-1 ). Higher median [IQR] CSF/plasma proCPU ratios were found
      in patients with stroke progression ((6.0 [4.2-6.9]) * 10-3 ) and poor outcome
      ((6.4 [3.9-7.0]) * 10-3 ) after 3 months (modified Rankin Scale; mRS > 3)
      compared with patients without progression ((3.9 [2.7-5.4]) * 10-3 ) or better
      outcome ((4.0 [2.8-5.0]) * 10-3 ). In stroke patients with a disrupted BBB,
      proCPU ratios were higher compared with stroke patients with an intact BBB ((6.4
      [5.8-9.0]) * 10-3 vs. (3.7 [2.8-5.0]) * 10-3 ). Conclusions ProCPU is increased
      in CSF during hyperacute ischemic stroke and is associated with stroke
      progression and outcome after 3 months, most likely due to BBB dysfunction in the
      hyperacute phase of ischemic stroke.

PMID- 29194930
TI  - Metabolic versatility of a novel N2 -fixing Alphaproteobacterium isolated from a
      marine oxygen minimum zone.
AB  - The N2 -fixing (diazotrophic) community in marine ecosystems is dominated by non
      cyanobacterial microorganisms. Yet, very little is known about their identity,
      function and ecological relevance due to a lack of cultured representatives. Here
      we report a novel heterotrophic diazotroph isolated from the oxygen minimum zone
      (OMZ) off Peru. The new species belongs to the genus Sagittula (Rhodobacteraceae,
      Alphaproteobacteria) and its capability to fix N2 was confirmed in laboratory
      experiments. Genome sequencing revealed that it is a strict heterotroph with a
      high versatility in substrate utilization and energy acquisition mechanisms.
      Pathways for sulfide oxidation and nitrite reduction to nitrous oxide are encoded
      in the genome and might explain the presence throughout the Peruvian OMZ. The
      genome further indicates that this novel organism could be in direct interaction
      with other microbes or particles. NanoSIMS analyses were used to compare the
      metabolic potential of S. castanea with single-cell activity in situ; however, N2
      fixation by this diazotroph could not be detected at the isolation site. While
      the biogeochemical impact of S. castanea is yet to be resolved, its abundance and
      widespread distribution suggests that its potential to contribute to the marine N
      input could be significant at a larger geographical scale.

PMID- 29194931
TI  - Antibiotic resistome in a large-scale healthy human gut microbiota deciphered by
      metagenomic and network analyses.
AB  - The human gut microbiota is an important reservoir of antibiotic resistance genes
      (ARGs). A metagenomic approach and network analysis were used to establish a
      comprehensive antibiotic resistome catalog and to obtain co-occurrence patterns
      between ARGs and microbial taxa in fecal samples from 180 healthy individuals
      from 11 different countries. In total, 507 ARG subtypes belonging to 20 ARG types
      were detected with abundances ranging from 7.12 * 10-7 to 2.72 * 10-1 copy of
      ARG/copy of 16S-rRNA gene. Tetracycline, multidrug, macrolide-lincosamide
      streptogramin, bacitracin, vancomycin, beta-lactam and aminoglycoside resistance
      genes were the top seven most abundant ARG types. The multidrug ABC transporter,
      aadE, bacA, acrB, tetM, tetW, vanR and vanS were shared by all 180 individuals,
      suggesting their common occurrence in the human gut. Compared to populations from
      the other 10 countries, the Chinese population harboured the most abundant ARGs.
      Moreover, LEfSe analysis suggested that the MLS resistance type and its subtype
      'ermF' were representative ARGs of the Chinese population. Antibiotic
      inactivation, antibiotic target alteration and antibiotic efflux were the
      dominant resistance mechanism categories in all populations. Procrustes analysis
      revealed that microbial phylogeny structured the antibiotic resistome. Co
      occurrence patterns obtained via network analysis implied that 12 species might
      be potential hosts of 58 ARG subtypes.

PMID- 29194932
TI  - Paper-Based Polymer Electrodes for Bioanalysis and Electrochemistry of
      Neurotransmitters.
AB  - This article describes the preparation and characterization of PEDOT-coated paper
      electrodes. Their specific behavior was investigated, especially the impact of
      electrode shape on the electrochemical properties. It was found that different
      electrode geometries promote different results, largely because of a potential
      drop in the bulk of the electrode material. More importantly, the suitability of
      these substrates for bio- and neurochemical analyses was investigated. The paper
      electrodes were found to offer better resistance to both protein and
      neurotransmitter foulings, in comparison to a planar electrode. Interestingly,
      long paper electrodes were more stable during sustained oxidation of dopamine and
      serotonin than short ones, possibly because of the conjunction of surface
      passivation and potential drop allowing for the site of oxidation to move along
      the electrode as fouling progresses.

PMID- 29194933
TI  - Association of metabolic syndrome with carotid thickening and plaque in the
      general population: A meta-analysis.
AB  - We performed a meta-analysis of population studies reporting data on carotid
      intima-media thickness and plaque in patients with and without metabolic syndrome
      (MetS) to provide a new piece of information on the relationship of MetS with
      both phenotypes of vascular damage. The Ovid MEDLINE, PubMed, and Cochrane
      CENTRAL databases were searched without time restriction up to December 31, 2016.
      Overall, 19 696 patients (22.2% with MetS) were included in eight studies. Common
      carotid intima-media thickness was greater in patients with MetS compared with
      those without it (788 +/- 47 MUm vs 727 +/- 44 MUm), with a standard means
      difference of 0.28 +/- 0.06 (P = .00003). Increased intima-media thickness in
      patients with MetS was paralleled by a higher prevalence of plaques. The present
      meta-analysis shows that MetS is associated with both ultrasonographic phenotypes
      of carotid damage. This finding is consistent with the view of MetS as a cluster
      of hemodynamic and nonhemodynamic factors promoting vascular hypertrophy and
      plaque.

PMID- 29194934
TI  - Hypergammaglobulinemia is a strong predictor of disease progression,
      hepatocellular carcinoma, and death in patients with compensated cirrhosis.
AB  - BACKGROUND & AIMS: The outcome of compensated cirrhosis may vary considerably and
      cannot be predicted by routinely performed tests at present. The aim of this
      study was to evaluate possible predictors of clinical evolution in patients with
      Child-Pugh (C-P) class A cirrhosis because of untreatable causes by analysing
      clinical/biochemical/instrumental parameters evaluated at the time of diagnosis
      and during the subsequent long-lasting follow-up. METHODS: Two hundred and
      seventy-two consecutive C-P class A cirrhotic patients (155 males; median age 63
      years, range 34-81) were analysed. All patients were followed up for a median
      time of 96 months (range 21-144) through periodically performed
      clinical/biochemical/ultrasonographic and esophagogastroduodenoscopic
      examinations. RESULTS: During the follow-up, 97 individuals (36%) were clinically
      stable, 104 (38%) developed hepatocellular carcinoma (HCC) and 71 (26%)
      progressed towards C-P class B/C without developing cancer. One hundred and
      thirty-one patients (48%) died or underwent liver transplantation. Multivariate
      regression analysis showed that clinical stability was significantly associated
      with older age (P < .001), the absence of diabetes (P = .04) and of oesophageal
      varices (P < .001), serum albumin >3.5 gr/dL (P = .01) and gamma globulin <1.8
      gr/dL (P = .01). HCC development was significantly associated with younger age (P
      = .01) and serum gamma globulin values >=1.8 gr/dL (P < .001). C-P score
      progression was associated with oesophageal varices (P < .001), lower serum
      albumin (P = .03) and cholesterol (P = .01) values, and hypergammaglobulinemia (P
      = .02). Death was associated with younger age (P < .001) and
      hypergammaglobulinemia (P = .01). Multivariate Cox regression analysis and Kaplan
      Meier's survival test confirmed that gammaglobulinemia >=1.8 g/dL was a
      significant predictor of death (P < .02, and P < .01 respectively). CONCLUSIONS:
      Hypergammaglobulinemia identifies C-P class A cirrhotic patients at higher risk
      of disease progression, HCC development and death.

PMID- 29194935
TI  - Node self-connections in network metrics.
AB  - Zamborain-Mason et al. (Ecol. Lett., 20, 2017, 815-831) state that they have
      newly proposed network metrics that account for node self-connections. Network
      metrics incorporating node self-connections, also referred to as intranode
      (intrapatch) connectivity, were however already proposed before and have been
      widely used in a variety of conservation planning applications.

PMID- 29194936
TI  - Spinosad-mediated effects on the walking ability, midgut, and Malpighian tubules
      of Africanized honey bee workers.
AB  - BACKGROUND: The global decline in Apis mellifera colonies is attributed to
      multiple factors, including pesticides. The bioinsecticide spinosad was initially
      recognized as safe for non-target organisms; however, its toxicity has been
      changing this view. Here, we investigated the survival, behavioral changes, and
      structural changes in the midgut and Malpighian tubules of A. mellifera treated
      orally with a spinosad formulation. RESULTS: The field-recommended concentration
      of spinosad killed 100% of the bees. The 5% and 50% lethal concentrations (LC5
      and LC50 , respectively) of spinosad altered the behavioral activity, reducing
      the walking distance and velocity, and increased the resting time in comparison
      to the control. The LC50 caused disorganization of the epithelia of tested organs
      and induced oxidative stress and cell death. CONCLUSIONS: The present work
      provides new insights into the debate about the role of bioinsecticides in the
      mortality of Africanized honey bees. Even at very low concentrations, the
      spinosad formulation was toxic to the vital organs midgut and Malpighian tubules
      and adversely affected walking behavior. This detailed evaluation of the impact
      of the bioinsecticide on A. mellifera will contribute to the clarification of
      disturbances probably caused by spinosad formulations, which can be used to
      develop more sustainable protocols in agriculture. (c) 2017 Society of Chemical
      Industry.

PMID- 29194937
TI  - Age-related new bone formation following the use of cancellous bone-block
      allografts for reconstruction of atrophic alveolar ridges.
AB  - BACKGROUND: An age-related decrease in the number of osteogenic progenitor cells
      may compromise bone augmentation. PURPOSE: Histomorphometrical assessment of age
      related new bone formation, following atrophic alveolar ridge reconstruction,
      using cancellous bone-block allografts. MATERIAL AND METHODS: Ninety-three
      consecutive patients (58 females and 35 males) were referred for implant
      supported restoration of 122 severe atrophic alveolar ridges. Alveolar ridge
      deficiency locations were classified as anterior maxilla (n = 58), posterior
      maxilla (n= 32), and posterior mandible (n = 32). A bony deficiency of at least 3
      mm horizontally and up to 3 mm vertically according to computerized tomography
      (CT) in the posterior mandible and anterior maxilla, served as inclusion
      criteria. In the posterior maxilla, a residual alveolar ridge up to 4 mm
      vertically according to CT served as inclusion criteria. Augmentation was
      performed by the use of cancellous bone-block allografts. Bone biopsies (9-month
      posterior maxilla, 4 months anterior maxilla and posterior mandible) of young
      (<=40 years) versus older (>40 years) patients were histomorphometrically
      evaluated. RESULTS: In the posterior maxilla, no statistically significant
      histomorphometric differences were noted. While at the anterior maxilla and
      posterior mandible, statistically significant more newly formed bone was found in
      young versus older individuals, respectively (38.6% vs 19.8%, P = 0.04 and 69% vs
      31%, P = .05). CONCLUSION: New bone formation following residual alveolar ridge
      bone grafting is age-related. Longer bone consolidation and healing time may be
      recommended for older individuals.

PMID- 29194938
TI  - Inorganic, Hybridized and Living Macrocellular Foams: "Out of the Box"
      Heterogeneous Catalysis.
AB  - With this personal account we show how the Integrative Chemistry, when combining
      the sol-gel process and concentrated emulsions, allows to trigger inorganic,
      hybrid or living materials when dedicated toward heterogeneous catalysis
      applications. In here we focus on 3D-macrocellular monolithic foams bearing
      hierarchical porosities and applications thereof toward heterogeneous catalysis
      where both activities and mass transport are enhanced. We thereby first depict
      the general background of emulsions, focusing on concentrated ones, acting as
      soft templates for the design of solid (HIPE) foams, HIPE being the acronym for
      High Internal Phase Emulsions while encompassing both sol-gel and polymer
      chemistry. Secondly we extend this approach toward the design of inorganic
      cellular materials labeled Si(HIPE) and hybrid organic-inorganic foams, labeled
      Organo-Si(HIPE), where heterogeneous catalysis applications are addressed
      considering acidic, metallic, enzymatic and bacterial-based modified Si-HIPE.
      Along, we will show how the fluid hydrodynamic within the macrocellular foams is
      offering advanced "out of the box" heterogeneous catalytic capabilities.

PMID- 29194941
TI  - Response to: "Renal allograft histology at 10 years after transplantation in the
      tacrolimus era: Evidence of pervasive chronic injury".

PMID- 29194940
TI  - The development of a 4D treatment planning methodology to simulate the tracking
      of central lung tumors in an MRI-linac.
AB  - PURPOSE: Targeting and tracking of central lung tumors may be feasible on the
      Elekta MRI-linac (MRL) due to the soft-tissue visualization capabilities of MRI.
      The purpose of this work is to develop a novel treatment planning methodology to
      simulate tracking of central lung tumors with the MRL and to quantify the
      benefits in OAR sparing compared with the ITV approach. METHODS: Full 4D-CT
      datasets for five central lung cancer patients were selected to simulate the
      condition of having 4D-pseudo-CTs derived from 4D-MRI data available on the MRL
      with real-time tracking capabilities. We used the MRL treatment planning system
      to generate two plans: (a) with a set of MLC-defined apertures around the target
      at each phase of the breathing ("4D-MRL" method); (b) with a fixed set of fields
      encompassing the maximum inhale and exhale of the breathing cycle ("ITV" method).
      For both plans, dose accumulation was performed onto a reference phase. To
      further study the potential benefits of a 4D-MRL method, the results were
      stratified by tumor motion amplitude, OAR-to-tumor proximity, and the relative
      OAR motion (ROM). RESULTS: With the 4D-MRL method, the reduction in mean doses
      was up to 3.0 Gy and 1.9 Gy for the heart and the lung. Moreover, the lung's
      V12.5 Gy was spared by a maximum of 300 cc. Maximum doses to serial organs were
      reduced by up to 6.1 Gy, 1.5 Gy, and 9.0 Gy for the esophagus, spinal cord, and
      the trachea, respectively. OAR dose reduction with our method depended on the
      tumor motion amplitude and the ROM. Some OARs with large ROMs and in close
      proximity to the tumor benefited from tracking despite small tumor amplitudes.
      CONCLUSIONS: We developed a novel 4D tracking methodology for the MRL for central
      lung tumors and quantified the potential dosimetric benefits compared with our
      current ITV approach.

PMID- 29194942
TI  - RNA interference technology in crop protection against arthropod pests, pathogens
      and nematodes.
AB  - Scientists have made significant progress in understanding and unraveling several
      aspects of double-stranded RNA (dsRNA)-mediated gene silencing during the last
      two decades. Now that the RNA interference (RNAi) mechanism is well understood,
      it is time to consider how to apply the acquired knowledge to agriculture and
      crop protection. Some RNAi-based products are already available for farmers and
      more are expected to reach the market soon. Tailor-made dsRNA as an active
      ingredient for biopesticide formulations is considered a raw material that can be
      used for diverse purposes, from pest control and bee protection against viruses
      to pesticide resistance management. The RNAi mechanism works at the messenger RNA
      (mRNA) level, exploiting a sequence-dependent mode of action, which makes it
      unique in potency and selectivity compared with conventional agrochemicals.
      Furthermore, the use of RNAi in crop protection can be achieved by employing
      plant-incorporated protectants through plant transformation, but also by non
      transformative strategies such as the use of formulations of sprayable RNAs as
      direct control agents, resistance factor repressors or developmental disruptors.
      In this review, RNAi is presented in an agricultural context (discussing products
      that have been launched on the market or will soon be available), and we go
      beyond the classical presentation of successful examples of RNAi in pest-insect
      control and comprehensively explore its potential for the control of plant
      pathogens, nematodes and mites, and to fight against diseases and parasites in
      beneficial insects. Moreover, we also discuss its use as a repressor for the
      management of pesticide-resistant weeds and insects. Finally, this review reports
      on the advances in non-transformative dsRNA delivery and the production costs of
      dsRNA, and discusses environmental considerations. (c) 2017 Society of Chemical
      Industry.

PMID- 29194943
TI  - Understanding of hypertension and heart failure in patients with type 2 diabetes
      by studying effects of sodium-glucose cotransporter 2 inhibitors on plasma B-type
      natriuretic peptide levels.

PMID- 29194944
TI  - Relationship between implant stability measurements obtained by insertion torque
      and resonance frequency analysis: A systematic review.
AB  - BACKGROUND: The primary stability of dental implants can be evaluated by
      insertion torque (IT) and resonance frequency analysis (RFA). OBJECTIVE: Assess
      the supposed relationship between the IT and RFA. MATERIALS AND METHODS: A
      systematic review was performed based on the PRISMA. The electronic search was
      performed in the PubMed, Web of Science, SCOPUS, Cochrane Library electronic,
      OVID, and Scielo databases. Manual searches were also performed. There was no
      restrictions regarding year of publication or language. The articles identified
      were assessed independently by 3 trained researchers. Clinical trials reporting
      the RFA values by means of implant stability quotient (ISQ) and IT were included.
      RESULTS: The electronic and manual searches yielded 2017 studies. Twelve studies
      were included in the systematic review. There was no statistically significant
      correlation between ISQ and IT (rs  = .366; P = .079). The quality of the
      evidence was downgraded by risk of bias and indirectness; and the certainty of
      the evidence was low. CONCLUSION: IT and RFA are independent and incomparable
      methods of measuring primary stability. Is important for clinicians to define
      only one method of evaluation for each implant.

PMID- 29194945
TI  - Generalized Synthesis of Ultrathin Cobalt-Based Nanosheets from
      Metallophthalocyanine-Modulated Self-Assemblies for Complementary Water
      Electrolysis.
AB  - The development of effective approaches for preparing large-area, self-standing,
      ultrathin metal-based nanosheets, which have proved to be favorable for catalytic
      applications such as water electrolysis, is highly desirable but remains a great
      challenge. Reported herein is a simple and versatile strategy to synthesize
      ultrathin Co3 O4 and CoP NSs consisting of close-packed nanoparticles by
      pyrolyzing cobalt(II) phthalocyanine/graphene oxide (CoPc/GO) assemblies in air
      and subsequent topotactic phosphidation while preserving the graphene-like
      morphology. The strong pi-pi stacking interactions between CoPc and GO, and the
      inhibiting effect of the tetrapyrrole-derived macrocycle for grain growth during
      the catalytic carbon gasification contribute to the NSs forming. The resulting
      homologous Co3 O4 and CoP NSs display outstanding catalytic activity in alkaline
      media toward the oxygen evolution reaction and the hydrogen evolution reaction,
      respectively, ascribed to the richly exposed active sites, and the expedited
      electrolyte/ion transmission path. The integrated asymmetrical two-electrode
      configuration also presents a superior cell voltage of 1.63 V at 10 mA cm-2 for
      overall water splitting, accompanied with the excellent durability during long
      term cycling. Further evidences validate that this strategy is appropriate to
      fabricate graphene-like ultrathin NSs of many other metal oxides, such as Fe2 O3
      , NiO, MoO3 , and mixed-metal oxides, for various applications.

PMID- 29194946
TI  - Greetings from the endoplasmic reticulum (ER): escaping ER thiol isomerases
      regulate thrombosis.

PMID- 29194947
TI  - FHBC, a Hexa-peri-hexabenzocoronene-Fluorene Hybrid: A Platform for Highly
      Soluble, Easily Functionalizable HBCs with an Expanded Graphitic Core.
AB  - Materials based upon hexa-peri-hexabenzocoronenes (HBCs) show significant promise
      in a variety of photovoltaic applications. There remains the need, however, for a
      soluble, versatile, HBC-based platform, which can be tailored by incorporation of
      electroactive groups or groups that can prompt self-assembly. The synthesis of a
      HBC-fluorene hybrid is presented that contains an expanded graphitic core that is
      highly soluble, resists aggregation, and can be readily functionalized at its
      vertices. This new HBC platform can be tailored to incorporate six electroactive
      groups at its vertices, as exemplified by a facile synthesis of a representative
      hexaaryl derivative of FHBC. Synthesis of new FHBC derivatives, containing
      electroactive functional groups that can allow controlled self-assembly, may
      serve as potential long-range charge-transfer materials for photovoltaic
      applications.

PMID- 29194939
TI  - Management of drug interactions with direct-acting antivirals in Dutch
      HIV/hepatitis C virus-coinfected patients: adequate but not perfect.
AB  - OBJECTIVES: Direct-acting antivirals (DAAs) for treatment of chronic hepatitis C
      virus (HCV) infection can cause drug-drug interactions (DDIs) with combination
      antiretroviral therapy (cART) and non-cART co-medication. We mapped how
      physicians manage DDIs between DAAs and co-medication and analysed treatment
      outcomes. METHODS: Data were prospectively collected as part of the ATHENA HIV
      observational cohort and retrospectively analysed. Dutch patients with HIV/HCV
      coinfection who initiated treatment with DAAs between January 2015 and May 2016
      were included. Co-medication 3 months prior to and during DAA therapy was
      identified. Potential DDIs with the DAAs were checked using http://hep
      druginteractions.org. DDIs were categorized as: (1) no interaction expected; (2)
      potential interaction; (3) contra-indication; (4) no recommendation. These
      categories were used to determine which patients switched or had a DDI during DAA
      therapy with co-medication. RESULTS: A total of 423 patients were treated with
      DAAs, of whom 418 (99%) used cART and 251 (59%) used non-cART co-medication.
      Before commencing DAA treatment, in 17 of 84 (20%) patients the non-cART co
      medication which could result in a category 2/3 DDI was discontinued before DAA
      initiation, including two of six (33%) prescriptions of category 3 drugs. A total
      of 196 of 418 (47%) patients had a category 2/3 DDI between their DAA regimen and
      cART. Category 2/3 DDIs were prevented by switching cART in 78 of 147 (53%) and
      47 of 49 (98%) patients. Overall, 367 of 423 (87%) patients have achieved a
      sustained virological response (33 in follow-up). CONCLUSIONS: Prescription
      patterns suggest that physicians are aware of potential DDIs between co
      medication and DAAs, in particular potential DDIs with cART. Greater awareness is
      needed concerning category 3 interactions between non-cART co-medication and
      DAAs.

PMID- 29194948
TI  - Chagosendines A - C, New Metal Complexes of Imidazole Alkaloids from the
      Calcareous Sponge Leucetta chagosensis.
AB  - Chemical examination of the bright yellow sponge Leucetta chagosensis resulted in
      the isolation of three new imidazole-based alkaloid complexes namely
      chagosendines A - C (1 - 3), together with known analogues pyronaamidine,
      naamidine J, and naamine C. Their structures were determined on the basis of
      extensive spectroscopic (IR, MS, NMR, and single-crystal X-ray diffraction)
      analysis in association with the chemical conversion. The isolated alkaloids
      together with three synthesized new homodimer complexes were evaluated for the
      cytotoxic activities against a panel of tumor cell lines. The copper complexes of
      imidazole alkaloids 2 and 3, as found from nature for the first time, exerted
      selective and remarkable activities against the tumor cell lines K562, HepG2, and
      HeLa.

PMID- 29194949
TI  - Metabolism of 2,4-dichlorophenoxyacetic acid contributes to resistance in a
      common waterhemp (Amaranthus tuberculatus) population.
AB  - BACKGROUND: Synthetic auxins such as 2,4-dichlorophenoxyacetic acid (2,4-D) have
      been widely used for selective control of broadleaf weeds since the mid-1940s. In
      2009, an Amaranthus tuberculatus (common waterhemp) population with 10-fold
      resistance to 2,4-D was found in Nebraska, USA. The 2,4-D resistance mechanism
      was examined by conducting [14 C] 2,4-D absorption, translocation and metabolism
      experiments. RESULTS: No differences were found in 2,4-D absorption or
      translocation between resistant and susceptible A. tuberculatus plants. Resistant
      plants metabolized [14 C] 2,4-D more rapidly than did susceptible plants. The
      half-life of [14 C] 2,4-D in susceptible plants was 105 h, compared with 22 h in
      resistant plants. Pretreatment with the cytochrome P450 inhibitor malathion
      inhibited [14 C] 2,4-D metabolism in resistant plants and reduced the 2,4-D dose
      required for 50% growth inhibition (GR50 ) of resistant plants by 7-fold to 27 g
      ha-1 , similar to the GR50 for susceptible plants in the absence of malathion.
      CONCLUSION: Our results demonstrate that rapid 2,4-D metabolism is a contributing
      factor to resistance in A. tuberculatus, potentially mediated by cytochrome P450.
      Metabolism-based resistance to 2,4-D could pose a serious challenge for A.
      tuberculatus control because of the potential for cross-resistance to other
      herbicides. (c) 2017 Society of Chemical Industry.

PMID- 29194953
TI  - Reptile embryos are not capable of behavioral thermoregulation in the egg.
AB  - Reptile embryos have recently been observed moving within the egg in response to
      temperature, raising the exciting possibility that embryos might behaviorally
      thermoregulate analogous to adults. However, the conjecture that reptile embryos
      have ample opportunity and capacity to adaptively control their body temperature
      warrants further discussion. Using turtles as a model, we discuss the
      spatiotemporal constraints to movement in reptile embryos. We demonstrate that,
      as embryos grow, the internal egg space rapidly diminishes such that the temporal
      window for appreciable displacement is confined to stages that feature incomplete
      neuromuscular differentiation. During this time, muscles are insufficiently
      developed to actively and consistently control movement. These constraints are
      well illustrated by the Chinese softshelled turtle (Pelodiscus sinensis), the
      first reptile reported to behaviorally thermoregulate. Furthermore, sporadic
      embryo activity peaks after the temperature-sensitive period in species with
      temperature-dependent sex determination, thus nullifying the opportunity for
      embryos to exhibit control over this important phenotype. These embryonic
      constraints add to previously-identified environmental constraints on behavioral
      thermoregulation by reptile embryos. We discuss alternative hypotheses to explain
      previously reported patterns of behavioral thermoregulation. Based on a holistic
      consideration of embryonic limitations, we conclude that reptile embryos are
      generally unable to adaptively behaviorally thermoregulate within the egg.

PMID- 29194951
TI  - Quantification of large scale DNA organization for predicting prostate cancer
      recurrence.
AB  - This study investigates whether Genomic Organization at Large Scales (which we
      propose to call GOALS) as quantified via nuclear phenotype characteristics and
      cell sociology features (describing cell organization within tissue) collected
      from prostate tissue microarrays (TMAs) can separate biochemical failure from
      biochemical nonevidence of disease (BNED) after radical prostatectomy (RP). Of
      the 78 prostate cancer tissue cores collected from patients treated with RP, 16
      who developed biochemical relapse (failure group) and 16 who were BNED patients
      (nonfailure group) were included in the analyses (36 cores from 32 patients). A
      section from this TMA was stained stoichiometrically for DNA using the Feulgen
      Thionin methodology, and scanned with a Pannoramic MIDI scanner. Approximately
      110 nuclear phenotypic features, predominately quantifying large scale DNA
      organization (GOALS), were extracted from each segmented nuclei. In addition, the
      centers of these segmented nuclei defined a Voronoi tessellation and subsequent
      architectural analysis. Prostate TMA core classification as biochemical failure
      or BNED after RP using GOALS features was conducted (a) based on cell type and
      cell position within the epithelium (all cells, all epithelial cells, epithelial
      >2 cell layers away from basement membrane) from all cores, and (b) based on
      epithelial cells more than two cell layers from the basement membrane using a
      Classifier trained on Gleason 6, 8, 9 (16 cores) only and applied to a Test set
      consisting of the Gleason 7 cores (20 cores). Successful core classification as
      biochemical failure or BNED after RP by a linear classifier was 75% using all
      cells, 83% using all epithelial cells, and 86% using epithelial >2 layers.
      Overall success of predicted classification by the linear Classifier of (b) was
      87.5% using the Training Set and 80% using the Test Set. Overall success of
      predicted progression using Gleason score alone was 75% for Gleason >7 as
      failures and 69% for Gleason >6 as failures. (c) 2017 International Society for
      Advancement of Cytometry.

PMID- 29194952
TI  - Deltamethrin is metabolized by CYP6FU1, a cytochrome P450 associated with
      pyrethroid resistance, in Laodelphax striatellus.
AB  - BACKGROUND: Cytochrome P450s (CYPs) are known to play a major role in
      metabolizing a wide range compounds. CYP6FU1 has been found to be over-expressed
      in a deltamethrin-resistant strain of Laodelphax striatellus. This study was
      conducted to express CYP6FU1 in Sf9 cells as a recombinant protein, to confirm
      its ability to degrade deltamethrin, chlorpyrifos, imidacloprid and traditional
      P450 probing substrates. RESULTS: Carbon monoxide difference spectrum analysis
      indicated that the intact CYP6FU1 protein was expressed in insect Sf9 cells.
      Catalytic activity tests with four traditional P450 probing substrates revealed
      that the expressed CYP6FU1 preferentially metabolized p-nitroanisole and
      ethoxyresorufin, but not ethoxycoumarin and luciferin-HEGE. The enzyme kinetic
      parameters were tested using p-nitroanisole. The michaelis constant (Km ) and
      catalytic constant (Kcat ) values were 17.51 +/- 4.29 um and 0.218 +/- 0.001 pmol
      min-1 mg-1 protein, respectively. Furthermore, CYP6FU1 activity for degradation
      of insecticides was tested by measuring substrate depletion and metabolite
      formation. The chromatogram analysis showed obvious nicotinamide-adenine
      dinucleotide phosphate (NADPH)-dependent depletion of deltamethrin, and formation
      of the unknown metabolite. Mass spectra and the molecular docking model showed
      that the metabolite was 4-hydroxy-deltamethrin. However, the recombinant CYP6FU1
      could not metabolize imidacloprid and chlorpyrifos. CONCLUSION: These results
      confirmed that the over-expressed CYP6FU1 contributes to deltamethrin resistance
      in L. striatellus, and p-nitroanisole might be a potential diagnostic probe for
      deltamethrin metabolic resistance detection and monitoring. (c) 2017 Society of
      Chemical Industry.

PMID- 29194956
TI  - At the MERcy of platelet primers.

PMID- 29194955
TI  - Incomplete penetrance, variable expressivity, or dosage insensitivity in four
      families with directly transmitted unbalanced chromosome abnormalities.
AB  - The direct transmission of microscopically visible unbalanced chromosome
      abnormalities (UBCAs) is rare and usually has phenotypic consequences. Here we
      report four families in which a normal phenotype was initially found in one or
      more family members. Each UBCA was interpreted with regard to overlapping
      examples and factors previously associated with transmitted imbalances including
      incidental ascertainment, low gene density, benign copy number variation (CNV)
      content, and gene relatedness. A 4.56 Mb deletion of 8p23.1-p23.2 was thought to
      be causal in the affected proband but showed incomplete penetrance in her mother
      and sibling (Family 1). Incomplete penetrance was also associated with a 10.88 Mb
      duplication of 13q21.31-q22.1 (Family 3) and dosage insensitivity with a 17.6 Mb
      deletion of 22pter-q11.21 (Family 4) that were both ascertained at prenatal
      diagnosis and each found in 4 unaffected family members. The 22pter-q11.21
      deletion is part of a region with high benign CNV content and supports the
      mapping of cat eye syndrome to a 600 kb interval of 22q11.1-q11.21. Low gene
      densities of less than 2.0 genes/Mb were found in each of these three families
      but only after segmentally duplicated genes were excluded from the deletions of
      8p and 22q. In contrast, gene density was average and variable expressivity
      associated with a 3.59 Mb duplication of 8p23.1 incidentally ascertained for
      paternal infertility (Family 2). Our results indicate that a greater degree of
      direct parental transmission, incomplete penetrance, and variable expression are
      features of both sub-microscopic CNVs and UBCAs with relatively low gene and high
      benign CNV content.

PMID- 29194950
TI  - Multiplex quantitative SILAC for analysis of archaeal proteomes: a case study of
      oxidative stress responses.
AB  - Stable isotope labelling of amino acids in cell culture (SILAC) is a quantitative
      proteomic method that can illuminate new pathways used by cells to adapt to
      different lifestyles and niches. Archaea, while thriving in extreme environments
      and accounting for ~20%-40% of the Earth's biomass, have not been analyzed with
      the full potential of SILAC. Here, we report SILAC for quantitative comparison of
      archaeal proteomes, using Haloferax volcanii as a model. A double auxotroph was
      generated that allowed for complete incorporation of 13 C/15 N-lysine and 13 C
      arginine such that each peptide derived from trypsin digestion was labelled. This
      strain was found amenable to multiplex SILAC by case study of responses to
      oxidative stress by hypochlorite. A total of 2565 proteins was identified by LC
      MS/MS analysis (q-value <= 0.01) that accounted for 64% of the theoretical
      proteome. Of these, 176 proteins were altered at least 1.5-fold (p-value < 0.05)
      in abundance during hypochlorite stress. Many of the differential proteins were
      of unknown function. Those of known function included transcription factor
      homologs related to oxidative stress by 3D-homology modelling and orthologous
      group comparisons. Thus, SILAC is found to be an ideal method for quantitative
      proteomics of archaea that holds promise to unravel gene function.

PMID- 29194954
TI  - COMT Val158 Met moderates the link between rank and aggression in a non-human
      primate.
AB  - The COMT Val158 Met polymorphism is one of the most widely studied genetic
      polymorphisms in humans implicated in aggression and the moderation of stressful
      life event effects. We screened a wild primate population for polymorphisms at
      the COMT Val158 Met site and phenotyped them for aggression to test whether the
      human polymorphism exists and is associated with variation in aggressive
      behavior. Subjects were all adults from 4 study groups (37 males, 40 females) of
      Assamese macaques (Macaca assamensis) in their natural habitat (Phu Khieo
      Wildlife Sanctuary, Thailand). We collected focal animal behavioral data (27
      males, 36 females, 5964 focal hours) and fecal samples for non-invasive DNA
      analysis. We identified the human COMT Val158 Met polymorphism (14 Met/Met, 41
      Val/Met and 22 Val/Val). Preliminary results suggest that COMT genotype and
      dominance rank interact to influence aggression rates. Aggression rates increased
      with rank in Val/Val, but decreased in Met/Met and Val/Met individuals, with no
      significant main effect of COMT genotype on aggression. Further support for the
      interaction effect comes from time series analyses revealing that when changing
      from lower to higher rank position Val/Val individuals decreased, whereas Met/Met
      individuals increased their aggression rate. Contradicting the interpretation of
      earlier studies, we show that the widely studied Val158 Met polymorphism in COMT
      is not unique to humans and yields similar behavioral phenotypes in a non-human
      primate. This study represents an important step towards understanding individual
      variation in aggression in a wild primate population and may inform human
      behavioral geneticists about the evolutionary roots of inter-individual variation
      in aggression.

PMID- 29194957
TI  - Improving medication adherence: The proof of the pudding will be in the eating.

PMID- 29194958
TI  - Biodegradable Nanoagents with Short Biological Half-Life for SPECT/PAI/MRI
      Multimodality Imaging and PTT Therapy of Tumors.
AB  - Rapid clearance of nanoagents is a critical criterion for their clinical
      translation. Herein, it is reported that biodegradable and renal clearable
      nanoparticles are potentially useful for image-guided photothermal therapy of
      tumors. The multifunctional nanoparticles with excellent colloidal stability are
      synthesized through coordination reactions between Fe3+ ions and gallic acid
      (GA)/polyvinyl pyrrolidone (PVP) in aqueous solution. Detailed characterization
      reveals that the resulting Fe3+ /GA/PVP complex nanoparticles (FGPNs) integrate
      strong near-infrared absorption with paramagnetism well. As a result, the FGPNs
      present outstanding performance for photoacoustic imaging and magnetic resonance
      imaging of tumors, and outstanding photothermal ablation effect for tumor therapy
      owing to their high photothermal conversion efficiency. More importantly, the
      pharmacokinetic behaviors of the FGPNs determined through 125 I labeling suggest
      that the FGPNs are readily degraded in vivo showing a short biological half-life,
      and the decomposition products are excreted through either renal clearance
      pathway or bowel elimination pathway via stomach, which highlights the
      characteristics of the current multifunctional theranostic agent and their
      potential in clinical translation.

PMID- 29194960
TI  - Toward Wearable Self-Charging Power Systems: The Integration of Energy-Harvesting
      and Storage Devices.
AB  - One major challenge for wearable electronics is that the state-of-the-art
      batteries are inadequate to provide sufficient energy for long-term operations,
      leading to inconvenient battery replacement or frequent recharging. Other than
      the pursuit of high energy density of secondary batteries, an alternative
      approach recently drawing intensive attention from the research community, is to
      integrate energy-generation and energy-storage devices into self-charging power
      systems (SCPSs), so that the scavenged energy can be simultaneously stored for
      sustainable power supply. This paper reviews recent developments in SCPSs with
      the integration of various energy-harvesting devices (including piezoelectric
      nanogenerators, triboelectric nanogenerators, solar cells, and thermoelectric
      nanogenerators) and energy-storage devices, such as batteries and
      supercapacitors. SCPSs with multiple energy-harvesting devices are also included.
      Emphasis is placed on integrated flexible or wearable SCPSs. Remaining challenges
      and perspectives are also examined to suggest how to bring the appealing SCPSs
      into practical applications in the near future.

PMID- 29194961
TI  - Computational simulation of postoperative pulmonary flow distribution in Alagille
      patients with peripheral pulmonary artery stenosis.
AB  - BACKGROUND: Up to 90% of individuals with Alagille syndrome have congenital heart
      diseases. Peripheral pulmonary artery stenosis (PPS), resulting in right
      ventricular hypertension and pulmonary flow disparity, is one of the most common
      abnormalities, yet the hemodynamic effects are ill-defined, and optimal patient
      management and treatment strategies are not well established. The purpose of this
      pilot study is to use recently refined computational simulation in the setting of
      multiple surgical strategies, to examine the influence of pulmonary artery
      reconstruction on hemodynamics in this population. MATERIALS AND METHODS: Based
      on computed tomography angiography and cardiac catheterization data, preoperative
      pulmonary artery models were constructed for 4 patients with Alagille syndrome
      with PPS (all male, age range: 0.6-2.9 years), and flow simulations with
      deformable walls were performed. Surgeon directed virtual surgery, mimicking the
      surgical procedure, was then performed to derive postoperative models.
      Postoperative simulation-derived hemodynamics and blood flow distribution were
      then compared with the clinical results. RESULTS: Simulations confirmed
      substantial resistance, resulting from preoperative severe ostial stenoses, and
      the use of newly developed adaptive outflow boundary conditions led to excellent
      agreement with in vivo measurements. Relief of PPS decreased pulmonary artery
      pressures and improved pulmonary flow distribution both in vivo and in silico
      with good correlation. CONCLUSIONS: Using adaptive outflow boundary conditions,
      computational simulations can estimate postoperative overall pulmonary flow
      distribution in patients with Alagille syndrome after pulmonary artery
      reconstruction. Obstruction relief along with pulmonary artery vasodilation
      determines postoperative pulmonary flow distribution and newer methods can
      incorporate these physiologic changes. Evolving blood flow simulations may be
      useful in surgical or transcatheter planning and in understanding the complex
      interplay among various obstructions in patients with peripheral pulmonary
      stenosis.

PMID- 29194959
TI  - Standardized hybrid living donor hemihepatectomy in adult-to-adult living donor
      liver transplantation.
AB  - The aim of this study was to analyze the outcomes of the most updated version and
      largest group of our standardized hybrid (laparoscopic mobilization and
      hepatectomy through midline incision) living donor (LD) hemihepatectomy compared
      with those from a conventional laparotomy in adult-to-adult living donor liver
      transplantation (LDLT). Of 237 adult-to-adult LDLTs from August 1997 to March
      2017, 110 LDs underwent the hybrid procedure. Preoperative and operative factors
      were analyzed and compared with conventional laparotomy (n = 126). The median
      duration of laparoscopic usage was 26 minutes in the hybrid group. Although there
      was improvement in applying this procedure over time from the beginning of the
      series of cases studied, blood loss and operative duration were still smaller and
      shorter in the hybrid group. There was no significant difference between the
      groups in the incidence of postoperative complications greater than or equal to
      Clavien-Dindo class III. There was no difference in recipient outcome between the
      groups. Our standardized procedure of hybrid LD hepatectomy is applicable and
      safe for all types of LD hepatectomies, and it enables the benefit of both the
      laparoscopic and the open approach in a transplant center without a laparoscopic
      expert. Liver Transplantation 24 363-368 2018 AASLD.

PMID- 29194962
TI  - Diagnostic Testing for Zika: Observing Rapid Translation During a Public Health
      Emergency.

PMID- 29194963
TI  - Simultaneous Detection of Protein and mRNA in Jurkat and KG-1a Cells by Mass
      Cytometry.
AB  - Mass cytometry uniquely enables high-dimensional single-cell analysis of complex
      populations. This recently developed technology is based on inductively coupled
      time-of-flight mass spectrometry for multiplex proteomic analysis of more than 40
      markers per cell. The ability to characterize the transcriptome is critical for
      the understanding of disease pathophysiology, medical diagnostics, and drug
      discovery. Current techniques allowing the in situ detection of transcripts in
      single cells are limited to a small number of simultaneous targets and are
      generally tedious and labor-intensive. In this report, we present the development
      of a multiplex method for targeted RNA detection by combining the mass cytometry
      and RNAscope(r) platforms. This novel assay, called Metal In Situ Hybridization
      (MISH), includes the hybridization of RNA-specific target probes followed by
      signal amplification achieved through a cascade of hybridization events, ending
      with the binding of amplifier-specific detector probes. The detector probes are
      tagged with isotopically pure metal atoms used for detection by mass cytometry.
      Proof-of-principle experiments show the simultaneous detection of three mRNA
      targets in Jurkat cells in suspension cell assay mode. The localization of
      transcripts was also investigated using the imaging mass cytometry platform in
      Jurkat and KG-1a cells. In addition, we optimized the antibody staining procedure
      to allow the co-detection of mRNA and cell surface markers. Our data demonstrate
      that MISH can be used to complement protein detection by mass cytometry as well
      as to investigate gene transcription and translation in single cells. (c) 2017
      International Society for Advancement of Cytometry.

PMID- 29194965
TI  - A denitrifying community associated with a major, marine nitrogen fixer.
AB  - The diazotrophic cyanobacterium, Trichodesmium, is an integral component of the
      marine nitrogen cycle and contributes significant amounts of new nitrogen to
      oligotrophic, tropical/subtropical ocean surface waters. Trichodesmium forms
      macroscopic, fusiform (tufts), spherical (puffs) and raft-like colonies that
      provide a pseudobenthic habitat for a host of other organisms including marine
      invertebrates, microeukaryotes and numerous other microbes. The diversity and
      activity of denitrifying bacteria found in association with the colonies was
      interrogated using a series of molecular-based methodologies targeting the gene
      encoding the terminal step in the denitrification pathway, nitrous oxide
      reductase (nosZ). Trichodesmium spp. sampled from geographically isolated ocean
      provinces (the Atlantic Ocean, the Red Sea and the Indian Ocean) were shown to
      harbor highly similar, taxonomically related communities of denitrifiers whose
      members are affiliated with the Roseobacter clade within the Rhodobacteraceae
      (Alphaproteobacteria). These organisms were actively expressing nosZ in samples
      taken from the mid-Atlantic Ocean and Red Sea implying that Trichodesmium
      colonies are potential sites of nitrous oxide consumption and perhaps earlier
      steps in the denitrification pathway also. It is proposed that coupled
      nitrification of newly fixed N is the most likely source of nitrogen oxides
      supporting nitrous oxide cycling within Trichodesmium colonies.

PMID- 29194964
TI  - The bridge between transplantation and regenerative medicine: Beginning a new
      Banff classification of tissue engineering pathology.
AB  - The science of regenerative medicine is arguably older than transplantation-the
      first major textbook was published in 1901-and a major regenerative medicine
      meeting took place in 1988, three years before the first Banff transplant
      pathology meeting. However, the subject of regenerative medicine/tissue
      engineering pathology has never received focused attention. Defining and
      classifying tissue engineering pathology is long overdue. In the next decades,
      the field of transplantation will enlarge at least tenfold, through a hybrid of
      tissue engineering combined with existing approaches to lessening the organ
      shortage. Gradually, transplantation pathologists will become tissue-(re-)
      engineering pathologists with enhanced skill sets to address concerns involving
      the use of bioengineered organs. We outline ways of categorizing abnormalities in
      tissue-engineered organs through traditional light microscopy or other modalities
      including biomarkers. We propose creating a new Banff classification of tissue
      engineering pathology to standardize and assess de novo bioengineered solid
      organs transplantable success in vivo. We recommend constructing a framework for
      a classification of tissue engineering pathology now with interdisciplinary
      consensus discussions to further develop and finalize the classification at
      future Banff Transplant Pathology meetings, in collaboration with the human cell
      atlas project. A possible nosology of pathologic abnormalities in tissue
      engineered organs is suggested.

PMID- 29194966
TI  - The use of custom-made dental splints for robotic and rigid endoscopic surgery of
      the upper aerodigestive tract.

PMID- 29194967
TI  - A New Facile Synthesis of Tungsten Oxide from Tungsten Disulfide: Structure
      Dependent Supercapacitor and Negative Differential Resistance Properties.
AB  - Tungsten oxide (WO3 ) is an emerging 2D nanomaterial possessing unique
      physicochemical properties extending a wide spectrum of novel applications which
      are limited due to lack of efficient synthesis of high-quality WO3 . Here, a
      facile new synthetic method of forming WO3 from tungsten sulfide, WS2 is
      reported. Spectroscopic, microscopic, and X-ray studies indicate formation of
      flower like aggregated nanosized WO3 plates of highly crystalline cubic phase via
      intermediate orthorhombic tungstite, WO3. H2 O phase. The charge storage ability
      of WO3 is extremely high (508 F g-1 at current density of 1 A g-1 ) at negative
      potential range compared to tungstite (194 F g-1 at 1 A g-1 ). Moreover, high
      (97%) capacity retention after 1000 cycles and capacitive charge storage nature
      of WO3 electrode suggest its supremacy as a negative electrode of
      supercapacitors. The asymmetric supercapacitor, based on the WO3 as a negative
      electrode and mildly reduced graphene oxide as a positive electrode, manifests
      high energy density of 218.3 mWhm-2 at power density 1750 mWm-2 , and
      exceptionally high power density, 17 500 mW m-2 , with energy density of 121.5
      mWh m-2 . Furthermore, the negative differential resistance (NDR) property of
      both WO3 and WO3 .H2 O are reported for the first time and NDR is explained with
      density of state approach.

PMID- 29194970
TI  - Headspace solid-phase microextraction and gas chromatographic analysis of low
      molecular-weight sulfur volatiles with pulsed flame photometric detection and
      quantification by a stable isotope dilution assay.
AB  - Low-molecular-weight volatile sulfur compounds such as thiols, sulfides,
      disulfides as well as thioacetates cause a sulfidic off-flavor in wines even at
      low concentration levels. The proposed analytical method for quantification of
      these compounds in wine is based on headspace solid-phase microextraction,
      followed by gas chromatographic analysis with sulfur-specific detection using a
      pulsed flame photometric detector. Robust quantification was achieved via a
      stable isotope dilution assay using commercial and synthesized deuterated
      isotopic standards. The necessary chromatographic separation of analytes and
      isotopic standards benefits from the inverse isotope effect realized on an apolar
      polydimethylsiloxane stationary phase of increased film thickness. Interferences
      with sulfur-specific detection in wine caused by sulfur dioxide were minimized by
      addition of propanal. The method provides adequate validation data, with good
      repeatability and limits of detection and quantification. It suits the
      requirements of wine quality management, allowing the control of oenological
      treatments to counteract an eventual formation of excessively high concentration
      of such malodorous compounds.

PMID- 29194969
TI  - Sex-based disparities in delisting for being "too sick" for liver
      transplantation.
AB  - Women with cirrhosis awaiting liver transplantation (LT) experience higher rates
      of waitlist mortality than men; it is unknown whether practices surrounding
      delisting for being "too sick" for LT contribute to this disparity beyond death
      alone. We conducted an analysis of patients listed for LT in the United Network
      for Organ Sharing/Organ Procurement and Transplantation Network not receiving
      exception points from May 1, 2007 to July 1, 2014 with a primary outcome of
      delisting with removal codes of "too sick" or "medically unsuitable." A total of
      44 388 patients were included; 4458 were delisted for being "too sick" for LT.
      Delisting was more frequent in women (11% vs 9%, P < .001). Compared to delisted
      men, delisted women differed in age (58 vs 57), non-hepatitis C virus listing
      diagnoses (69% vs 56%), hepatic encephalopathy (36% vs 31%), height (161.9 vs
      177.0 cm), private insurance (47% vs 52%), and Karnofsky performance status (60
      vs 70) (P < .001 for all). There were no differences in Model for End-Stage Liver
      Disease including serum sodium and Child Pugh Scores. A competing risk analysis
      demonstrated that female sex was independently associated with a 10% (confidence
      interval 2%-18%) higher risk of delisting when accounting for rates of death and
      transplantation and adjusting for confounders. This study demonstrates a
      significant disparity in delisting practices by sex, highlighting the need for
      better assessments of sickness, particularly in women.

PMID- 29194968
TI  - Overexpression of cytochrome P450 CYP6BG1 may contribute to chlorantraniliprole
      resistance in Plutella xylostella (L.).
AB  - BACKGROUND: The diamondback moth Plutella xylostella (L.) is the most widely
      distributed pest of cruciferous crops and has developed resistance to most
      commonly used insecticides, including chlorantraniliprole. Resistance to
      chlorantraniliprole is likely caused by mutations of the target, the ryanodine
      receptor, and/or mediated by an increase in detoxification enzyme activities.
      Although target-site resistance is documented in detail, resistance mediated by
      increased metabolism has rarely been reported. RESULTS: The activity of
      cytochrome P450 was significantly higher in two resistant P. xylostella
      populations than in a susceptible one. Among ten detected cytochrome P450 genes,
      CYP6BG1 was significantly overexpressed (over 80-fold) in a field-resistant
      population compared with expression in a susceptible one. Knockdown of CYP6BG1 by
      RNA interference dramatically reduced the 7-ethoxycoumarin-O-deethylase (7-ECOD)
      activity of P450 by 45.5% and increased the toxicity of chlorantraniliprole
      toward P. xylostella by 26.8% at 48 h postinjection of double-stranded RNA. By
      contrast, overexpression of CYP6BG1 in a transgenic Drosophila melanogaster line
      significantly decreased the toxicity of the insecticide to the transgenic flies.
      CONCLUSIONS: Overexpression of CYP6BG1 may contribute to chlorantraniliprole
      resistance in P. xylostella. Our findings will provide new insights into the
      mechanisms of resistance to diamide insecticides in other insect pests. (c) 2017
      Society of Chemical Industry.

PMID- 29194971
TI  - The causes, significance and consequences of inflammatory fibrosis in kidney
      transplantation: The Banff i-IFTA lesion.
AB  - Inflammation within areas of interstitial fibrosis and tubular atrophy (i-IFTA)
      is associated with adverse outcomes in kidney transplantation. We evaluated i
      IFTA in 429 indication- and 2052 protocol-driven biopsy samples from a
      longitudinal cohort of 362 kidney-pancreas recipients to determine its
      prevalence, time course, and relationships with T cell-mediated rejection (TCMR),
      immunosuppression, and outcome. Sequential histology demonstrated that i-IFTA was
      preceded by cellular interstitial inflammation and followed by IF/TA. The
      prevalence and intensity of i-IFTA increased with developing chronic fibrosis and
      correlated with inflammation, tubulitis, and immunosuppression era (P < .001).
      Tacrolimus era-based immunosuppression was associated with reduced histologic
      inflammation in unscarred and scarred i-IFTA compartments, ameliorated
      progression of IF, and increased conversion to inactive IF/TA (compared with
      cyclosporine era, P < .001). Prior acute (including borderline) TCMR and
      subclinical TCMR were followed by greater 1-year i-IFTA, remaining predictive by
      multivariate analysis and independent of humoral markers. One-year i-IFTA was
      associated with accelerated IF/TA, arterial fibrointimal hyperplasia, and chronic
      glomerulopathy and with reduced renal function (P < .001 versus no i-IFTA). In
      summary, i-IFTA is the histologic consequence of active T cell-mediated
      alloimmunity, representing the interface between inflammation and tubular injury
      with fibrotic healing. Uncontrolled i-IFTA is associated with adverse structural
      and functional outcomes.

PMID- 29194972
TI  - A composite noninvasive index correlates with liver fibrosis scores in post
      Fontan patients: Preliminary findings.
AB  - OBJECTIVE: We hypothesized that clinic-based, hepatic-ultrasound, elastography
      measurements, either alone or in combination with other noninvasive variables,
      might correlate with liver-biopsy fibrosis scores in patients post-Fontan.
      METHODS: Between March 2012 and February 2017, we identified patients post-Fontan
      that underwent elective cardiac catheterization and simultaneous transvenous
      hepatic biopsy. From this group, we selected patients that met inclusion criteria
      for liver-ultrasound, shear-wave elastography. Utilizing the results of
      elastography, laboratory testing, and time post-Fontan, we constructed a
      composite Fontan hepatic index as a sum of elastography measurements in
      kilopascals, model for end-stage liver disease excluding INR scores, and the
      square root of the number of years post-Fontan. Further, we analyzed correlations
      between Fontan hepatic index values and fibrosis scores from hepatic biopsy.
      RESULTS: We identified a total of 79 post-Fontan patients that underwent cardiac
      catheterization and liver biopsy. Of the 79 patients, 53 met inclusion criteria,
      and 32 consented to undergo hepatic-ultrasound elastography. Of the 32 that
      underwent elastography, data from 30 patients was used for analysis. We found no
      statistically significant differences in demographics, laboratory values, or
      cardiac catheterization data between the 30 included patients and the 21 that did
      not participate. Utilizing data from the 30 included patients, we found a strong,
      highly statistically significant correlation between the Fontan hepatic index
      values and total fibrosis scores (R = 0.8, P < .00001). However, the cohort size
      prevented reliable discriminating cut-off values for the range of total fibrosis
      scores. CONCLUSIONS: In a small cohort of patients post-Fontan, preliminary
      findings suggest that the composite Fontan hepatic index might be a clinically
      useful, noninvasive method of serially monitoring for hepatic fibrosis. Further
      studies, with large patient cohorts, are necessary to validate our findings and
      develop clinically useful discriminatory cutoff values.

PMID- 29194973
TI  - Perovskite Quantum Dots and Their Application in Light-Emitting Diodes.
AB  - Perovskite quantum dots (PQDs) attract significant interest in recent years
      because of their unique optical properties, such as tunable wavelength, narrow
      emission, and high photoluminescence quantum efficiency (PLQY). Recent studies
      report new types of formamidinium (FA) PbBr3 PQDs, PQDs with organic-inorganic
      mixed cations, divalent cation doped colloidal CsPb1-x Mx Br3 PQDs (M = Sn2+ ,
      Cd2+ , Zn2+ , Mn2+ ) featuring partial cation exchange, and heterovalent cation
      doped into PQDs (Bi3+ ). These PQD analogs open new possibilities for
      optoelectronic devices. For commercial applications in lighting and backlight
      displays, stability of PQDs requires further improvement to prevent their
      degradation by temperature, oxygen, moisture, and light. Oxygen and moisture
      facilitated ion migration may easily etch unstable PQDs. Easy ion migration may
      result in crystal growth, which lowers PLQY of PQDs. Surface coating and
      treatment are important procedures for overcoming such factors. In this study,
      new types of PQDs and a strategy of improving their stabilities are introduced.
      Finally, this paper discusses future applications of PQDs in light-emitting
      diodes.

PMID- 29194975
TI  - Biofilm recruitment under nanofiltration conditions: the influence of resident
      biofilm structural parameters on planktonic cell invasion.
AB  - It is now generally accepted that biofouling is inevitable in pressure-driven
      membrane processes for water purification. A large number of published articles
      describe the development of novel membranes in an effort to address biofouling in
      such systems. It is reasonable to assume that such membranes, even those with
      antimicrobial properties, when applied in industrial-scale systems will
      experience some degree of biofouling. In such a scenario, an understanding of the
      fate of planktonic cells, such as those entering with the feed water, has
      important implications with respect to contact killing particularly for membranes
      with antimicrobial properties. This study thus sought to investigate the fate of
      planktonic cells in a model nanofiltration biofouling system. Here, the
      interaction between auto-fluorescent Pseudomonas putida planktonic cells and 7
      day-old Pseudomonas fluorescens resident biofilms was studied under permeate flux
      conditions in a nanofiltration cross flow system. We demonstrate that biofilm
      cell recruitment during nanofiltration is affected by distinctive biofilm
      structural parameters such as biofilm depth.

PMID- 29194976
TI  - The effect of adjuvant radiotherapy on radial forearm free flap volume after soft
      palate reconstruction in 13 patients.

PMID- 29194977
TI  - Coffee-Waste Templating of Metal Ion-Substituted Cobalt Oxides for the Oxygen
      Evolution Reaction.
AB  - A facile and scalable method using coffee waste grounds as a hard template has
      been developed to fabricate nanostructured Co3 O4 for the oxygen evolution
      reaction (OER). Co3 O4 incorporating metals with different valences (M/Co=1:4;
      M=Cu, Ni, Fe, Cr, and W) were also prepared with similar sheet-like structures
      comprising nanosized crystallites. After detailed characterization by X-ray
      diffraction, electron microscopy, and nitrogen sorption, the oxides were employed
      as OER electrocatalysts. Substitution of octahedral and tetrahedral sites of the
      spinel structure with divalent and trivalent transition metals (Cu, Ni, Fe, and
      Cr) increased the activity of Co3 O4 for the OER, whereas incorporation of
      hexavalent W led to formation of a second crystal phase and significantly higher
      electrocatalytic performance. Furthermore, this method is easily scaled up for
      mass production of Co3 O4 with the same nanostructure, which is highly desirable
      for large-scale application.

PMID- 29194974
TI  - Serum fetuin-B is positively associated with intrahepatic triglyceride content
      and increases the risk of insulin resistance in obese Chinese adults: A cross
      sectional study.
AB  - BACKGROUND: Fetuin-B impairs insulin action in myotubes and hepatocytes and
      causes glucose intolerance in mice. This study explored the correlation between
      serum fetuin-B and intrahepatic triglyceride (IHTG) content, and the association
      between fetuin-B and the risk of insulin resistance in the general adult
      population. METHODS: A cross-sectional study of 1318 obese adults who underwent
      serum fetuin-B testing and hepatic ultrasonography was conducted in Xiamen,
      China. The IHTG content was determined in 428 subjects by magnetic resonance
      spectroscopy. RESULTS: Non-alcoholic fatty liver disease prevalence was
      significantly higher in those with the highest serum fetuin-B concentrations and
      the highest IHTC content (Tertile 3) than in subjects in Tertiles 1 and 2 (62.6%
      vs 60.7% and 54.3%, respectively [P = 0.032], and 15.3% vs 12.8% and 12.7%,
      respectively [P = 0.049]). There was a significant association between increasing
      serum fetuin-B tertiles and both increasing fasting insulin concentrations (mean
      [+/- SD] 11.9 +/- 6.8, 12.7 +/- 7.6, and 13.3 +/- 6.4 mIU/L in Tertiles 1, 2 and
      3, respectively; P = 0.006) and prevalence of insulin resistance (54.4%, 58.9%,
      and 64.5% in Tertiles 1, 2 and 3, respectively; P = 0.010). In linear regression
      analysis, IHTG content was independently and positively correlated with serum
      fetuin-B (regression coefficient 0.015; P = 0.045). With adjustment for potential
      confounders, serum fetuin-B was independently associated with increased risk of
      insulin resistance, with an adjusted odds ratio per standard deviation increase
      in fetuin-B of 1.14 (95% confidence interval 1.01-1.30; P = 0.031). CONCLUSIONS:
      The results demonstrate the role of fetuin-B linking liver fat accumulation to
      insulin resistance in humans.

PMID- 29194978
TI  - A Novel Regulatory Mechanism for Differentiation of Mesenchymal Stem Cell: Redox
      State of DJ-1 Matters.
AB  - Reactive oxygen species (ROS) are multifunctional gas transmitters with diverse
      biological actions (adverse vs beneficial) dependent on their level. The
      differentiation of vascular stem cells into smooth muscle cells (SMCs) might be
      involved in the pathogenesis of cardiovascular disorders including hypertension
      and atherosclerosis. Therefore, controlling the differentiation of vascular stem
      cells is a potential strategy for the treatment of vascular diseases.
      Nonetheless, it remains to be revealed whether ROS could mediate the
      differentiation of mesenchymal stem cells (MSCs) into SMCs. In addition, there
      are no redox (reduction-oxidation)-sensitive molecules identified, which are
      responsible for the ROS-induced differentiation of MSCs. In article number
      1700208, Baek et al. [Proteomics 2017, 17, Issue 21] found that ROS mediate the
      differentiation of MSCs into SMCs through the modification of redox states of a
      multifunctional ROS-responsive protein, DJ-1, revealing a novel regulatory
      mechanism for differentiation of MSCs into SMCs and shedding light into the
      future development of stem-cell-targeted pharmacotherapy.

PMID- 29194980
TI  - Polar solar panels: Arctic and Antarctic microbiomes display similar taxonomic
      profiles.
AB  - Solar panels located on high (Arctic and Antarctic) latitudes combine the
      harshness of the climate with that of the solar exposure. We report here that
      these polar solar panels are inhabited by similar microbial communities in
      taxonomic terms, dominated by Hymenobacter spp., Sphingomonas spp. and
      Ascomycota. Our results suggest that solar panels, even on high latitudes, can
      shape a microbial ecosystem adapted to irradiation and desiccation.

PMID- 29194982
TI  - Synthesis of Monofunctionalized Silsesquioxanes (RSiMe2 O)(iBu)7 Si8 O12 via
      Alkene Hydrosilylation.
AB  - The research presented in this work comprehensively describes hydrosilylation of
      a wide spectrum of alkenes which contain one or more reactive groups with (HSiMe2
      O)(iBu)7 Si8 O12 , in the presence of different types of catalysts. Special
      attention is paid to the influence of alkene, catalyst, and reaction conditions
      on process effectiveness and selectivity by the precise monitoring of the
      experiments with in situ FTIR and NMR spectroscopies. More than twenty
      silsesquioxanes bearing reactive groups (OH, Br, NR2 , CO, COOR, NCO, epoxy, SiR3
      ) commonly used in organic and polymer chemistry, were obtained, isolated and
      characterized by 1 H, 13 C, 29 Si NMR and MALDI TOF. Importantly, in the
      presented syntheses, commercially available reagents and catalysts were used,
      meaning that the presented methods could be easily repeated, rapidly scaled up,
      and widely applied.

PMID- 29194981
TI  - ddrage: A data set generator to evaluate ddRADseq analysis software.
AB  - High-throughput sequencing makes it possible to evaluate thousands of genetic
      markers across genomes and populations. Reduced-representation sequencing
      approaches, like double-digest restriction site-associated DNA sequencing
      (ddRADseq), are frequently applied to screen for genetic variation. In particular
      in nonmodel organisms where whole-genome sequencing is not yet feasible, ddRADseq
      has become popular as it allows genomewide assessment of variation patterns even
      in the absence of other genomic resources. However, while many tools are
      available for the analysis of ddRADseq data, few options exist to simulate
      ddRADseq data in order to evaluate the accuracy of downstream tools. The
      available tools either focus on the optimization of ddRAD experiment design or do
      not provide the information necessary for a detailed evaluation of different
      ddRAD analysis tools. For this task, a ground truth, that is, the underlying
      information of all effects in the data set, is required. Therefore, we here
      present ddrage, the ddRAD Data Set Generator, that allows both developers and
      users to evaluate their ddRAD analysis software. ddrage allows the user to adjust
      many parameters such as coverage and rates of mutations, sequencing errors or
      allelic dropouts, in order to generate a realistic simulated ddRADseq data set
      for given experimental scenarios and organisms. The simulated reads can be easily
      processed with available analysis software such as stacks or pyrad and evaluated
      against the underlying parameters used to generate the data to gauge the impact
      of different parameter values used during downstream data processing.

PMID- 29194984
TI  - A gene encoding a DUF523 domain protein is involved in the conversion of 2
      thiouracil into uracil.
AB  - Modified nucleotides are present in many RNA species in all Domains of Life.
      While the biosynthetic pathways of such nucleotides are well studied, much less
      is known about the degradation of RNAs and the return to the metabolism of
      modified nucleotides, their respective nucleosides or heterocyclic bases. Using
      an E. coli uracil auxotroph, we screened the metagenomic libraries for genes,
      which would allow the conversion of 2-thiouracil to uracil and thereby lead to
      the growth on a defined synthetic medium. We show that a gene encoding a protein
      consisting of previously uncharacterized Domain of Unknown Function 523 (DUF523)
      is responsible for such phenotype. We have purified this recombinant protein and
      demonstrated that it contains a Fe?S cluster. The substitution of cysteines,
      which have been predicted to form such clusters, with alanines abolished the
      growth phenotype. We conclude that DUF523 is involved in the conversion of 2
      thiouracil into uracil in vivo.

PMID- 29194979
TI  - Synthesis, adenosine receptor binding and molecular modelling studies of novel
      thieno[2,3-d]pyrimidine derivatives.
AB  - A series of new molecules containing a thieno[2,3-d]pyrimidine scaffold was
      synthesized and characterized by adopting an efficient synthetic scheme. The
      effect of a free or substituted amino group at 2-position as well as an oxo
      group, imidazole or 1,2,4-triazole ring at 4-position of the scaffold on the
      affinity and selectivity towards adenosine receptors (ARs) was evaluated.
      Compounds 17-19 with a free amino group at 2-position along with the presence of
      an imidazole/1,2,4-triazole ring at 4-position of the scaffold showed selective
      binding affinities for hA2A AR, whereas carbamoylation of the amino group at 2
      position (in the presence of an oxo-group at 4-position of the scaffold)
      increased the affinity and selectivity of certain compounds (7-10) for hA3 AR.
      Molecular dynamic simulation study of one of the most active compound 8 (Ki hA1 
      > 30 MUm, hA2A  = 0.65 MUm, and hA3  = 0.124 MUm) revealed the role of important
      amino acid residues for imparting good affinity towards hA3 and hA2A ARs.
      Molecular docking studies were carried out for other compounds using the crystal
      structure of hA2A AR and a homology model of hA3 AR to rationalize their
      structure-activity relationships. The molecular docking results were in agreement
      with the experimental binding affinity data of ARs.

PMID- 29194983
TI  - Translational Development of Microbiome-Based Therapeutics: Kinetics of E. coli
      Nissle and Engineered Strains in Humans and Nonhuman Primates.
AB  - Understanding the pharmacology of microbiome-based therapeutics is required to
      support the development of new medicines. Strains of E. coli Nissle (EcN) were
      genetically modified and administered to cynomolgus monkeys at doses of 1 * 109
      and 1 * 1012 colony-forming units (CFU)/day for 28 days. A clinical study to
      evaluate the exposure and clearance of EcN in healthy volunteers was also
      performed. Healthy subjects received oral doses of EcN, 2.5 to 25 * 109 CFU 3
      times daily for 28 days or a single day. In cynomolgus monkeys, replicating
      strains yielded higher fecal concentrations than nonreplicating strains and
      persisted for longer following cessation of dosing. In the clinical study, all
      subjects cleared EcN following cessation of dosing with median clearance of 1
      week. Quantitative methodology can be applied to microbiome-based therapeutics,
      and similar kinetics and clearance were observed for EcN in cynomolgus monkeys
      and humans.

PMID- 29194987
TI  - Coexistence of poribacterial phylotypes among geographically widespread and
      phylogenetically divergent sponge hosts.
AB  - Marine sponges are benthic 'filter-feeding' invertebrates that can host dense and
      diverse bacterial, archaeal and eukaryotic communities. Due to the finding of
      several genes encoding symbiosis factors, such as adhesins, ankyrin repeats and
      tetratricopeptide repeats, the candidate phylum 'Poribacteria' is considered as a
      promising model microorganism for studying the origin of host-symbiont
      interactions in sponges. However, relatively little is known about its global
      diversity and phylogenetic distribution among different sponge hosts. Therefore,
      in this study we investigated phylogenetic relationships among poribacterial
      phylotypes and generated a phylogenetic network to examine the distribution and
      intraspecific diversity of the phylotypes between phylogenetically divergent host
      sponges at a global scale. For this study 361 poribacterial 16S rRNA gene
      sequences obtained by Sanger sequencing from 15 different countries and 8 marine
      regions were gathered. We could demonstrate that the candidate phylum
      'Poribacteria' is composed of diverse phylotypes, which are distributed among a
      wide range of phylogenetically divergent sponge hosts. The current phylogenetic
      analyses found neither conclusive evidence for co-speciation with its hosts, nor
      biogeographical correlation. Moreover, we identified a novel poribacterial clade,
      which might represent a link between the previously established four
      'Poribacteria' clades.

PMID- 29194988
TI  - Selective Electrogenerative Oxidation of 5-Hydroxymethylfurfural to 2,5
      Furandialdehyde.
AB  - 2,5-furandialdehyde (DFF) was synthesized by electrogenerative oxidation of 5
      hydroxymethylfurfural (HMF) over a PtRu catalyst with 89 % selectivity at 50 
      degrees C after 17 h. This approach opens an avenue for a selective, energy
      efficient and green oxidation of biomass-derived platform alcohols to added-value
      chemicals.

PMID- 29194985
TI  - A multiplex reverse transcription PCR and automated electronic microarray assay
      for detection and differentiation of seven viruses affecting swine.
AB  - Microarray technology can be useful for pathogen detection as it allows
      simultaneous interrogation of the presence or absence of a large number of
      genetic signatures. However, most microarray assays are labour-intensive and time
      consuming to perform. This study describes the development and initial evaluation
      of a multiplex reverse transcription (RT)-PCR and novel accompanying automated
      electronic microarray assay for simultaneous detection and differentiation of
      seven important viruses that affect swine (foot-and-mouth disease virus [FMDV],
      swine vesicular disease virus [SVDV], vesicular exanthema of swine virus [VESV],
      African swine fever virus [ASFV], classical swine fever virus [CSFV], porcine
      respiratory and reproductive syndrome virus [PRRSV] and porcine circovirus type 2
      [PCV2]). The novel electronic microarray assay utilizes a single, user-friendly
      instrument that integrates and automates capture probe printing, hybridization,
      washing and reporting on a disposable electronic microarray cartridge with 400
      features. This assay accurately detected and identified a total of 68 isolates of
      the seven targeted virus species including 23 samples of FMDV, representing all
      seven serotypes, and 10 CSFV strains, representing all three genotypes. The assay
      successfully detected viruses in clinical samples from the field, experimentally
      infected animals (as early as 1 day post-infection (dpi) for FMDV and SVDV, 4 dpi
      for ASFV, 5 dpi for CSFV), as well as in biological material that were spiked
      with target viruses. The limit of detection was 10 copies/MUl for ASFV, PCV2 and
      PRRSV, 100 copies/MUl for SVDV, CSFV, VESV and 1,000 copies/MUl for FMDV. The
      electronic microarray component had reduced analytical sensitivity for several of
      the target viruses when compared with the multiplex RT-PCR. The integration of
      capture probe printing allows custom onsite array printing as needed, while
      electrophoretically driven hybridization generates results faster than
      conventional microarrays that rely on passive hybridization. With further
      refinement, this novel, rapid, highly automated microarray technology has
      potential applications in multipathogen surveillance of livestock diseases.

PMID- 29194986
TI  - Alga-Made Anti-Hepatitis B Antibody Binds to Human Fcgamma Receptors.
AB  - Microalgae are unicellular eukaryotic organisms which represent an emerging
      alternative to other cell biofactories commonly used to produce monoclonal
      antibodies. Microalgae display several biotechnological advantages such as their
      rapid growth rate and their phototrophic lifestyle allowing low production costs
      as protein expression is solar-fueled. Recently, a fully assembled recombinant
      IgG antibody directed against Hepatitis B surface antigen is produced and
      secreted in the culture medium of the diatom Phaeodactylum tricornutum. A
      biochemical characterization of this recombinant antibody demonstrated that the
      Asn-297 is N-glycosylated by oligomannosides. In the immune system, antibodies
      interact with effector molecules and cells through their Fc part and the
      recognition of Fcgamma receptors (FcgammaR) which are important for inducing
      phagocytosis of opsonized microbes. Interactions between IgG and FcgammaR are
      influenced by the N-glycan structures present on the Asn-297. In this study, the
      authors characterized the binding capacity of the anti-hepatitis B recombinant
      IgG produced in P. tricornutum to two human Fcgamma receptors (FcgammaRI and
      IIIa) using a cellular binding assay and surface plasmon resonance (SPR). This
      allowed us to demonstrate that the alga-made antibody is able to bind FcgammaRI
      with a reduced affinity and engages FcyRIIIa with 3-times higher affinity
      compared to a control human IgG1.

PMID- 29194989
TI  - Contralateral neck metastases in lateralised, resectable advanced stage
      oropharyngeal squamous cell carcinoma-Results of 57 patients undergoing bilateral
      selective neck dissection.

PMID- 29194990
TI  - Effect of testosterone supplementation on nitroso-redox imbalance, cardiac
      metabolism markers, and S100 proteins expression in the heart of castrated male
      rats.
AB  - The aim of this study was to investigate the effects of castration and
      testosterone supplementation on nitroso-redox status, cardiac metabolism markers,
      and S100 proteins expression in the heart of male rats. 50 male Wistar rats were
      randomized into five groups with ten animals each: group 1: control intact (CON);
      group 2: sham operated (Sh-O); group 3: sesame oil-treated rats (S-oil); group 4:
      gonadoectomized (GDX); and group 5: gonadoectomized rats treated with
      testosterone (GDX-T) for 8 weeks. Our results showed myofibrillar weaving,
      apoptosis, inflammation, and fibrosis (as reflected by increased activity of MMP
      9 and MMP 2) in the heart of gonadoectomized rats. Testosterone supplementation
      restored the normal structure of the heart. In addition, a state of nitroso-redox
      imbalance was observed in the heart of castrated rats with increased NO (425.1 +/
      322.8 vs. 208 +/- 67.06, p ? 0.05) and MDA (33.18 +/- 9.45 vs. 22.04 +/- 7.13, p
      ? 0.05) and decreased GSH levels (0.71 +/- 0.13 vs. 1.09 +/- 0.19, p = 0.001).
      Testosterone treatment leads to a re-establish of only NO levels (425.1 +/- 322.8
      vs. 210.4 +/- 114.3, p > 0.05). Markers of cardiac metabolism showed an
      enhancement of LDH activity (12725 +/- 4604 vs. 5381 +/- 3122, p ? 0.05) in the
      heart of castrated rats. This was inversed by testosterone replacement (12725 +/-
      4604 vs. 5781 +/- 5187, p ? 0.05). Furthermore, castration induced heart's
      accumulation of triglycerides (37.24 +/- 6.17 vs. 27.88 +/- 6.47, p ? 0.05) and
      total cholesterol (61.44 +/- 3.59 vs. 54.11 +/- 7.55, p ? 0.05), which were
      significantly reduced by testosterone supplementation (29.03 +/- 2.47 vs. 37.24
      +/- 6.17, p ? 0.05) and (47.9 +/- 4.15 vs. 61.44 +/- 3.59, p ? 0.001).
      Cardiomyocytes of castrated rats showed a decreased immunoexpression of S100
      proteins compared to control animals. A restoration of S100 proteins
      immunostaining in cardiomyocyte cytoplasm was observed after testosterone
      supplementation. These findings confirm the deleterious effects of testosterone
      deficiency on cardiac function and highlight the involvement of nitric oxide,
      metalloproteinases 2 and 9, and S100 proteins.

PMID- 29194992
TI  - Monosaccharide Derivatives with Low-Nanomolar Lectin Affinity and High
      Selectivity Based on Combined Fluorine-Amide, Phenyl-Arginine, Sulfur-pi, and
      Halogen Bond Interactions.
AB  - The design of small and high-affinity lectin inhibitors remains a major challenge
      because the natural ligand binding sites of lectin are often shallow and have
      polar character. Herein we report that derivatizing galactose with un-natural
      structural elements that form multiple non-natural lectin-ligand interactions
      (orthogonal multipolar fluorine-amide, phenyl-arginine, sulfur-pi, and halogen
      bond) can provide inhibitors with extraordinary affinity (low nanomolar) for the
      model lectin, galectin-3, which is more than five orders of magnitude higher than
      the parent galactose; moreover, is selective over other galectins.

PMID- 29194991
TI  - Haemorrhage following transoral robotic surgery.
AB  - BACKGROUND: To report our experience of postoperative haemorrhage in patients
      following transoral robotic surgery (TORS). METHODS: Data were collected on
      patients having TORS. Postoperative haemorrhage within 30 days was graded using
      the Mayo Clinic grading system. RESULTS: Transoral robotic surgery operations
      were performed on 122 patients. There were 23 bleeding events classified as minor
      to severe following 19 operations (16%). Haemorrhage requiring a return to the
      operating room occurred after 7 operations (6%). The odds of an emergent
      haemorrhage were 5.19 times greater in patients who had a staged neck dissection
      after TORS (P = .05). The odds of a postoperative bleeding event were 2.6 times
      greater in patients receiving a larger resection (P = .107). There were no
      haemorrhage events in the 36 patients who received a synchronous neck dissection
      with transcervical ligation of the external carotid artery. CONCLUSIONS: Surgical
      intervention for TORS haemorrhage occurred in 6% patients. No haemorrhage
      occurred in patients who had ligation of the external carotid artery.

PMID- 29194993
TI  - Nonstoichiometric Cux Iny S Quantum Dots for Efficient Photocatalytic Hydrogen
      Evolution.
AB  - Unlike their bulk counterpart, Cux Iny S quantum dots (QDs) prepared by an
      aqueous synthetic approach, show promising activity for photocatalytic hydrogen
      evolution, which is competitive with the state-of-the-art Cd chalcogen QDs.
      Moreover, the as-prepared Cux Iny S QDs with In-rich composition show much better
      efficiency than the stoichiometric ones (Cu/In=1:1).

PMID- 29194997
TI  - Piecing together cis-regulatory networks: insights from epigenomics studies in
      plants.
AB  - 5-Methylcytosine, a chemical modification of DNA, is a covalent modification
      found in the genomes of both plants and animals. Epigenetic inheritance of
      phenotypes mediated by DNA methylation is well established in plants. Most of the
      known mechanisms of establishing, maintaining and modifying DNA methylation have
      been worked out in the reference plant Arabidopsis thaliana. Major functions of
      DNA methylation in plants include regulation of gene expression and silencing of
      transposable elements (TEs) and repetitive sequences, both of which have
      parallels in mammalian biology, involve interaction with the transcriptional
      machinery, and may have profound effects on the regulatory networks in the cell.
      Methylome and transcriptome dynamics have been investigated in development and
      environmental responses in Arabidopsis and agriculturally and ecologically
      important plants, revealing the interdependent relationship among genomic
      context, methylation patterns, and expression of TE and protein coding genes.
      Analyses of methylome variation among plant natural populations and species have
      begun to quantify the extent of genetic control of methylome variation vs. true
      epimutation, and model the evolutionary forces driving methylome evolution in
      both short and long time scales. The ability of DNA methylation to positively or
      negatively modulate binding affinity of transcription factors (TFs) provides a
      natural link from genome sequence and methylation changes to transcription.
      Technologies that allow systematic determination of methylation sensitivities of
      TFs, in native genomic and methylation context without confounding factors such
      as histone modifications, will provide baseline datasets for building cell-type-
      and individual-specific regulatory networks that underlie the establishment and
      inheritance of complex traits. This article is categorized under: Laboratory
      Methods and Technologies > Genetic/Genomic Methods Biological Mechanisms >
      Regulatory Biology.

PMID- 29194995
TI  - The dynamic metabolomic changes throughout mouse epididymal lumen fluid
      potentially contribute to sperm maturation.
AB  - Epididymal lumen fluids are directly responsible for sperm maturation. However,
      very little is known about the molecular details of small molecule metabolites in
      the epididymal lumen fluids until now. Here we identified and compared the
      metabolic profiles of mouse caput and cauda epididymal lumen fluids using GC-MS
      technique. Among 236 metabolites identified in caput and cauda epididymis, 36
      were significantly enriched in caput epididymis while 18 were significantly
      enriched in cauda epididymis. Pathway analysis identified ascorbate and aldarate
      metabolism and beta-alanine metabolism as most relevant pathways in caput and
      cauda epididymis, respectively. Ascorbate, dehydroascorbic acid and beta-alanine
      associated with these two pathways were firstly reported in mouse epididymal
      lumen fluids and might play important roles in sperm maturation.

PMID- 29194996
TI  - Effects of pioglitazone treatment on blood leptin levels in patients with type 2
      diabetes.
AB  - AIMS/INTRODUCTION: The aim of the present study was to carry out a meta-analysis
      of randomized controlled trials (RCTs) that investigated the effects of
      pioglitazone on blood leptin levels in patients with type 2 diabetes. MATERIALS
      AND METHODS: Literature searches were carried out using Medline, the Cochrane
      Controlled Trials Registry and ClinicalTrials.gov, and RCTs that investigated the
      effects of pioglitazone on blood leptin levels in patients with type 2 diabetes
      were selected. Standardized mean differences and 95% confidence intervals were
      calculated. RESULTS: A total of 10 RCTs met the eligibility criteria and were
      included in the meta-analysis. Significantly lower blood leptin levels were
      observed in the pioglitazone group (standardized mean difference -0.58, 95%
      confidence interval -1.12 to -0.05%, P = 0.03) than in the placebo group. There
      was no significant difference in blood leptin levels observed between the
      pioglitazone and oral antidiabetic drug groups (standardized mean difference 
      0.01, 95% confidence interval -0.20 to 0.19%, P = 0.93). CONCLUSIONS: There was a
      significant difference in blood leptin levels between the pioglitazone and
      placebo groups. However, relatively few RCTs were included in the study, and
      there was a high level of statistical heterogeneity; we believe that this could
      have affected the results.

PMID- 29194994
TI  - The inner-rod component of Shigella flexneri type 3 secretion system, MxiI, is
      involved in the transmission of the secretion activation signal by its
      interaction with MxiC.
AB  - The virulence of Shigella mainly resides in the use of a Type 3 Secretion System
      (T3SS) to inject several proteins inside the host cell. Three categories of
      proteins are hierarchically secreted: (1) the needle components (MxiH and MxiI),
      (2) the translocator proteins which form a pore (translocon) inside the host cell
      membrane, and (3) the effectors interfering with the host cell signaling
      pathways. In the absence of host cell contact, the T3SS is maintained in an "off"
      state by the presence of a tip complex. We have previously identified a
      gatekeeper protein, MxiC, which sequesters effectors inside the bacteria probably
      by interacting with MxiI, the inner-rod component. Upon cell contact and
      translocon insertion, a signal is most likely transmitted from the top of the
      needle to the base, passing through the needle and allowing effectors release.
      However, the molecular mechanism underlying the transmission of the activation
      signal through the needle is still poorly understood. In this work, we
      investigate the role of MxiI in the activation of the T3SS by performing a
      mutational study. Interestingly we have shown that mutations of a single residue
      in MxiI (T82) induce an mxiC-like phenotype and prevent the interaction with
      MxiC. Moreover, we have shown that the L26A mutation significantly reduces T3
      secretion. The L26A mutation impairs the interaction between MxiI and Spa40, a
      keystone component of the switch between needle assembly and translocators
      secretion. The L26A mutation also sequesters MxiC. All these results highlight
      the crucial role of MxiI in regulating the secretion and transmitting the
      activation signal of the T3SS.

PMID- 29194998
TI  - Emerging technologies for home-based semen analysis.
AB  - With about 70 million cases of infertility worldwide, half of which are caused by
      male factors, sperm analysis is critical to determine male fertility potential.
      Conventional semen analysis methods involve complex and manual inspection with a
      microscope, and these methods are labor intensive and can take several days. Due
      to unavailability of rapid, convenient, and user-friendly semen analysis tools,
      many men do not seek medical evaluation, especially in resource-constrained
      settings. Furthermore, as conventional methods have to be conducted in the
      laboratories, many men are unwilling to be tested as a result of social stigma in
      certain regions of the world. One solution can be found in at-home sperm
      analysis, which allows men to test their semen without the hassle of going to and
      paying for a clinic. Herein, we examine current at-home sperm analysis
      technologies and compare them to the traditional laboratory-based methods. In
      addition, we discuss emerging sperm analysis approaches and describe their
      limitations and future directions.

PMID- 29194999
TI  - Computational Screening of Doped alpha-MnO2 Catalysts for the Oxygen Evolution
      Reaction.
AB  - Minimizing energy and materials costs for driving the oxygen evolution reaction
      (OER) is paramount for the commercialization of water electrolysis cells and
      rechargeable metal-air batteries. Structural stability, catalytic activity, and
      electronic conductivity of pure and doped alpha-MnO2 for the OER are studied
      using density functional theory calculations. As model surfaces, we investigate
      the (110) and (100) facets, on which three possible active sites are identified:
      a coordination unsaturated, a bridge, and a bulk site. For pure and Cr-, Fe-, Co
      , Ni-, Cu-, Zn-, Cd-, Mg-, Al-, Ga-, In-, Sc-, Ru-, Rh-, Ir-, Pd-, Pt-, Ti-, Zr-,
      Nb-, and Sn-doped alpha-MnO2 , the preferred valence at each site is imposed by
      adding/subtracting electron donors (hydrogen atoms) and electron acceptors
      (hydroxy groups). From a subset of stable dopants, Pd-doped alpha-MnO2 is
      identified as the best catalyst and the only material that can outperform
      pristine alpha-MnO2 . Different approaches to increase the bulk electron
      conductivity of semiconducting alpha-MnO2 are discussed.

PMID- 29195001
TI  - Foot Barriers in Patients With Early Rheumatoid Arthritis: An Interview Study
      Among Swedish Women and Men.
AB  - OBJECTIVE: Foot impairments are related to reduced mobility and participation
      restrictions in daily activities in patients with established rheumatoid
      arthritis (RA). The new biologic medications are effective and reduce disease
      activity, but not disability to the same extent. Foot impairments are assumed to
      be related to participation restrictions also in patients with early RA,
      diagnosed after the introduction of biologic medications. Knowledge of foot
      impairments needs to be explored further after the introduction of biologic
      disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to
      explore the patients' perspective of foot impairments related to early RA.
      METHODS: The sample included 59 patients (ages 20-63 years) who were interviewed
      about participation dilemmas in daily life using the critical incident technique.
      The interviews were audio-recorded and transcribed. Data related to foot
      impairments were extracted and analyzed thematically. A research partner
      validated the analysis. RESULTS: Patients with early RA described a variety of
      participation restrictions related to foot impairments: foot hindrances in
      domestic life, foot impairments influencing work, leisure activities restricted
      by one's feet, struggling to be mobile, and foot impairments as an early sign of
      rheumatic disease. CONCLUSION: There is a need to focus on foot impairments
      related to early RA, and for health care professionals to understand these signs.
      A suggestion for future research is to conduct a longitudinal followup of foot
      impairment related to medication, disease activity, and disability in patients
      diagnosed after the introduction of bDMARDs.

PMID- 29195000
TI  - Internal Ophthalmic Arteries Within the Brain-Base Arterial System in Guinea Pig.
AB  - In situ vascular specimens of the arterial circle were collected from 15 adult
      guinea pigs, both male and female. After specimen preparation, the vessels were
      filled with synthetic latex and subjected to analysis. Similar as in the case of
      other rodents, vertebral arteries were merged into basilar artery, further
      dividing into two short terminal branches. Distally, the terminal branches extend
      into caudal cerebral arteries. Rostral part of the arterial circle of brain is
      supplied with blood from maxillary arteries via external and internal ophthalmic
      arteries connected by a short anastomosis. This type of vascularity may probably
      be considered a functional analogy to the internal carotid arteries observed in
      other species. Rostral and caudal parts of the arterial circle of brain are
      connected by exceptionally long caudal communicating arteries. In author's
      opinion, the disputable contribution of internal carotid artery and the
      exceptional contribution of internal ophthalmic arteries in the cerebral blood
      supply in guinea pigs as compared to other rodents, warrants further research on
      the subject. Anat Rec, 301:887-891, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29195003
TI  - Teaching pediatric cardiology with meaning and sense.
AB  - Pediatric cardiologists teach complicated concepts to a diverse group of learners
      that include medical students, nurses, residents, fellows, patients, and parents.
      Unfortunately, much of what is taught is not retained. In order to increase the
      likelihood of long-term retention, a cardiologist should teach with both meaning
      and sense. The authors provide a review of these concepts and give specific
      examples of how to teach in ways that both make sense and are meaningful to a
      cardiologist's leaners.

PMID- 29195002
TI  - Validation of Classification Criteria of Macrophage Activation Syndrome in
      Japanese Patients With Systemic Juvenile Idiopathic Arthritis.
AB  - OBJECTIVE: To validate whether the 2016 American College of Rheumatology/European
      League Against Rheumatism classification criteria of macrophage activation
      syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA) is
      practical in the real world. METHODS: A combination of expert consensus and
      analysis of real patient data was conducted by a panel of 15 pediatric
      rheumatologists. A total of 65 profiles comprised 18 patients with systemic JIA
      associated MAS and 47 patients with active systemic JIA without evidence of MAS.
      From these profiles, 10 patient data points for full-blown MAS, 11 patient data
      points for MAS onset, and 47 patient data points for acute systemic JIA without
      MAS were evaluated. RESULTS: Evaluation of the classification criteria to
      discriminate full-blown MAS from acute systemic JIA without MAS showed a
      sensitivity of 1.000 and specificity of 1.000 at the time of full-blown MAS.
      Sensitivity was 0.636 and specificity was 1.000 at the time of MAS onset. The
      number of measurement items that fulfilled the criteria increased in full-blown
      MAS compared to that at MAS onset. At MAS onset, the positive rates of patients
      who met the criteria for platelet counts and triglycerides were low, whereas
      those for aspartate aminotransferase were relatively high. At full-blown MAS, the
      number of patients who met the criteria for each measurement item increased.
      CONCLUSION: The classification criteria for MAS complicating systemic JIA had a
      very high diagnostic performance. However, the diagnostic sensitivity for MAS
      onset was relatively low. For the early diagnosis of MAS in systemic JIA, the
      dynamics of laboratory values during the course of MAS should be further
      investigated.

PMID- 29195004
TI  - Optimized fluorescent proteins for the rhizosphere-associated bacterium Bacillus
      mycoides with endophytic and biocontrol agent potential.
AB  - Tracking of fluorescent protein (FP)-labelled rhizobacteria is a key prerequisite
      to gain insights into plant-bacteria interaction mechanisms. However, the
      performance of FPs mostly has to be optimized for the bacterial host and for the
      environment of intended application. We report on the construction of mutational
      libraries of the superfolder green fluorescent protein sfGFP and the red
      fluorescent protein mKate2 in the bacterium B. mycoides, which next to its
      potential as plant-biocontrol agent occasionally enters an endophytic lifestyle.
      By fluorescence-activated cell sorting and comparison of signal intensities at
      the colony and single-cell level, the variants sfGFP(SPS6) and mKate (KPS12) with
      significantly increased brightness were isolated. Their high applicability for
      plant-bacteria interaction studies was shown by confocal laser scanning
      microscopy tracking of FP-tagged B. mycoides strains after inoculation to Chinese
      cabbage plants in a hydroponic system. During the process of colonization, strain
      EC18 rapidly attached to plant roots and formed a multicellular matrix,
      especially at the branching regions of the root hair, which probably constitute
      entrance sites to establish an endophytic lifestyle. The universal applicability
      of the novels FPs was proven by expression from a weak promoter, dual-labelling
      of B. mycoides, and by excellent expression and detectability in additional soil-
      and rhizosphere-associated Bacillus species.

PMID- 29195006
TI  - Actin biophysics in the tradition of Fumio Oosawa: A special issue with
      contributions from participants at the 2016 "Now in Actin" meeting in Nagoya.

PMID- 29195007
TI  - Systemic vasculitis developed after immune checkpoint inhibition: comment on the
      article by Cappelli et al.

PMID- 29195005
TI  - Synthetic Indolactam V Analogues as Inhibitors of PAR2-Induced Calcium
      Mobilization in Triple-Negative Breast Cancer Cells.
AB  - Human proteinase-activated receptor 2 (PAR2), a transmembrane G-protein-coupled
      receptor (GPCR), is an attractive target for a novel anticancer therapy, as it
      plays a critical role in cell migration and invasion. Selective PAR2 inhibitors
      therefore have potential as anti-metastatic drugs. Knowing that the natural
      product teleocidin A2 is able to inhibit PAR2 in tumor cells, the goal of the
      present study was to elaborate structure-activity relationships and to identify
      potent PAR2 inhibitors with lower activity against the adverse target, protein
      kinase C (PKC). For this purpose, an efficient gram-scale total synthesis of
      indolactam V (i.e., the parent structure of all teleocidins) was developed, and a
      library of derivatives was prepared. Some compounds were indeed found to exhibit
      high potency as PAR2 inhibitors at low nanomolar concentrations with improved
      selectivity (relative to teleocidin A2). The pseudopeptidic fragment bridging the
      C3 and C4 positions of the indole core proved to be essential for target binding,
      whereas activity and target selectivity depends on the substituents at N1 or C7.
      This study revealed novel derivatives that show high efficacy in PAR2 antagonism
      combined with increased selectivity.

PMID- 29195009
TI  - Ontogeny of Surface Texture of Limb Bones in Modern Aquatic Birds and
      Applicability of Textural Ageing.
AB  - Despite its importance in various disciplines, a general method to assess
      ontogenetic ages of skeletal and fossil specimens has been lacking for birds.
      Although the textural ageing method was formulated to assess relative ontogenetic
      ages of specimens from inspection of bone surface textures, the exact
      correspondence of surface textures to ontogenetic stages has not yet been clear.
      In this study, bone surface textures of six major limb bones (humerus, ulna,
      carpometacarpus, femur, tibiotarsus, and tarsometatarsus) were described in
      postnatal ontogenies of four species of modern birds (Calonectris leucomelas,
      Phalacrocorax capillatus, Larus crassirostris, and Cerorhinca monocerata) from 14
      to 28 individuals of known ontogenetic stages for each species. Consistently with
      the previous postulation, it was found that bones of chicks were characterized by
      rough surface textures with numerous grooves/depressions that host minute
      foramina. Bones of fledglings/juveniles, which are generally as large as those of
      adults but more slender, were characterized by the occasional presence of
      depressions and foramina. Histological observations confirmed that these rough
      surface textures were underlain by fibrolamellar bone tissue which is associated
      with active periosteal ossification. These results indicate that the smooth
      surface texture in adults is formed after the cessation of circumferential bone
      growth, which probably takes place between fledging and the attainment of sexual
      maturity. The available evidence suggests that the textural ageing is probably
      applicable to the entire Neognathae, a clade containing most crown-group birds.
      Anat Rec, 301:1026-1045, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29195008
TI  - Consensus Predictive Model for Human K562 Cell Growth Inhibition through Enalos
      Cloud Platform.
AB  - beta-Thalassemia is an inherited hematologic disorder caused by various mutations
      of the beta-globin gene, thus resulting in a significant decrease in adult
      hemoglobin (HbA) production. An increase in fetal hemoglobin (HbF) levels by drug
      molecules is considered of great potential in beta-thalassemia treatment and is
      expected to counterbalance the impaired production of HbA. In this work, based on
      a set of 129 experimentally tested biological inhibitors, we developed and
      validated a computational model for the prediction of K562 functional inhibition,
      possibly associated with HbF induction. To facilitate future advancements in the
      field, we incorporated our model into Enalos Cloud Platform, which enabled online
      access to our computational scheme (http://enalos.insilicotox.com/K562) through a
      user-friendly interface. This web service is offered to the wider community to
      promote in silico drug discovery through fast and reliable predictions.

PMID- 29195010
TI  - A Library of Multipurpose Supramolecular Supergelators: Fabrication of Structured
      Silica, Porous Plastics, and Fluorescent Gels.
AB  - Supramolecular gels find applications in various fields. Usually, a specific
      gelator is useful only for a specific application. This one-gelator-one
      application format is one factor that limits the usefulness of supramolecular
      gels. We report the synthesis of a library of gelators from a common core by
      using a click-chemistry approach. Thus, the click reaction of beta-azido-4,6-O
      benzylidene-galactopyranoside (1) with various alkynes gave 11 different gelators
      having varying gelation abilities. Whereas gelators having alkyl-chain
      substituents congealed alkanes and tetraethylorthosilicate (TEOS), the gelators
      having aromatic substituents congealed aromatic solvents. We exploited this
      difference in gelling behavior in the templated synthesis of silica rods and
      porous plastics. The styrene gel of gelator 2 j was polymerized, and the gelator
      was removed by washing to obtain porous polystyrene. The TEOS gel of gelator 2 b
      was polymerized to silica, and the gelator template was removed by calcination to
      give microstructured silica rods. We also developed fluorescent gelator 2 f by
      this method, which might find applications by virtue of its fluorescence in the
      assembled state.

PMID- 29195011
TI  - Experiences With Telehealth Followup in Patients With Rheumatoid Arthritis: A
      Qualitative Interview Study.
AB  - OBJECTIVE: To explore the experiences of a patient-reported outcome (PRO)-based
      telehealth followup from the perspective of patients with rheumatoid arthritis
      (RA) and their experiences of increasing their active role, and responsibility
      for disease control in particular. METHODS: Adopting a strategy of interpretive
      description, we conducted individual, semistructured interviews with 15 RA
      patients participating in a telehealth followup. Participants were selected
      purposively and consecutively from both sexes and with various ages, disease
      durations, and disease severity. The analysis was inductive, with a constant
      comparative approach. First, we identified the main themes conveying the
      participants' experiences. Then we constructed patient typologies to explain
      different perspectives on the telehealth followup. RESULTS: Five themes covered
      the participants' experiences: a flexible solution, responsibility, knowledge of
      RA, communication and involvement, and continuity. Two typologies, the keen
      patient and the reluctant patient, represented opposite perspectives and
      preferences regarding the core value of and approach to the telehealth followup.
      CONCLUSION: The participants had positive perceptions of the PRO-based telehealth
      followup and saw it as a flexible and resource-saving solution. They reported
      disadvantages related to missing face-to-face contact with health professionals.
      The 2 typologies, the keen and the reluctant patient, help us understand the
      patients' different needs, wishes, and abilities to take part in telehealth
      followup. Our findings reveal a need for more insight into how telehealth
      followup could be integrated in routine clinical practice, paying special
      attention to how reluctant patients may be supported.

PMID- 29195015
TI  - Does using testicular sperm retrieval rather than ejaculated spermatozoa improve
      reproductive outcomes in couples with previous ART failure and poor ovarian
      response? A case-controlled study.
AB  - The objective of this study was to assess whether testicular-retrieved
      spermatozoa improve reproductive outcomes compared to fresh ejaculate in women
      with poor ovarian response and a history of previous ART failure. The study was
      performed as a retrospective case-control study at a university-based
      reproductive center in Montreal, Quebec, Canada. Eighteen poor-responder patients
      were matched 3 : 1 with 54 controls. Poor responders were defined as those with
      <=3 oocytes retrieved at oocyte pickup. Cases were identified as poor responders,
      and only those with previous IVF failure(s) as an indication for testicular
      retrieved spermatozoa were included. Controls were age and cycle attempt number
      matched. All patients were included only once. From January 1, 2009 to December
      31, 2015, all patients and controls underwent an IVF cycle using ICSI with either
      testicular spermatozoa or ejaculated spermatozoa, respectively. Outcomes included
      live birth rate, pregnancy rate, miscarriage rate, oocyte number, and embryo
      transfer (ET) day. The results showed live birth rates, pregnancy rates, and
      miscarriage rates were similar. There were fewer day 2 ETs (8.5% vs. 48.6%, p =
      0.01) and more day 5 blastocyst transfers (25.0% vs. 5.4%, p = 0.05) in the
      testicular sperm retrieval group compared to controls and thus an overall
      suggestion of better embryo quality in the testicular sperm group. Overall,
      however, the use of testicular sperm retrieval appears to add little. Women with
      poor ovarian response typically have a poor prognosis with respect to live birth
      rates, and this is further supported in this study. The suggestion of better
      embryo quality in the testicular-retrieved sperm group would need to be further
      assessed in a larger multicentered study.

PMID- 29195012
TI  - The association between varicocoeles and vascular disease: an analysis of U.S.
      claims data.
AB  - S?tudies have suggested an association between varicocele, hypogonadism, and
      elevated oxidative stress markers, but no other health risks have been associated
      with varicoceles. ????We sought to determine the association between varicocele
      and incident medical comorbidities.
      ?????????????????????????????????????????????Using the Truven Health
      MarketScan(r) claims database from 2001 to 2009, we identified 4459 men with
      varicoceles, and 100,066 controls based on ICD-9 and CPT codes, with an average
      follow-up of 3.1 person years. Men with varicoceles were classified as
      symptomatic or asymptomatic based on co-existing diagnoses. Men with medical
      comorbidities present before or within 1 year of index diagnosis were excluded.
      Metabolic and cardiovascular outcome variables were identified via ICD-9 codes. A
      Cox regression analysis was used to assess incident risk of metabolic and
      cardiovascular disease amongst the different groups. Men with varicoceles had a
      higher incidence of heart disease compared to men who underwent infertility
      testing (HR 1.22, 95% CI: 1.03-1.45), and men who underwent vasectomy (HR 1.32,
      95% CI 1.13-1.54). The varicoceles group also had a higher risk of diabetes (HR
      1.73, 95% CI: 1.37-2.18) and hyperlipidemia (HR 1.15, 95% CI: 1.03-1.28) compared
      to the vasectomy group. Furthermore, men with symptomatic varicoceles (n = 3442)
      had a higher risk of heart disease, diabetes, and hyperlipidemia following
      diagnosis, while men with asymptomatic varicoceles (n = 1017) did not. Given the
      prevalence of varicoceles, further research is needed to understand the
      implications of a varicocele to a man's overall health.

PMID- 29195018
TI  - Dendron-Grafted Polylysine-Based Dual-Modal Nanoprobe for Ultra-Early Diagnosis
      of Pancreatic Precancerosis via Targeting a Urokinase-Type Plasminogen Activator
      Receptor.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer
      death. Early detection of precancerous pancreatic intraepithelial neoplasia
      (PanIN) tissues is an urgent challenge to improve the PDAC prognosis. Here, a
      urokinase-type plasminogen activator receptor (uPAR)-targeted magnetic resonance
      (MR)/near-infrared fluorescence (NIRF) dual-modal nanoprobe dendron-grafted
      polylysine (DGL)-U11 for ultra-early detection of pancreatic precancerosis is
      reported. Because of its good biocompatibility and biodegradability, globular
      architecture, and well-defined reactive groups, the DGL is chosen as the platform
      to load with a pancreatic tumor-targeting peptide U11, a magnetic resonance
      contrast agent Gd3+ -diethylene triamine pentaacetic acid, and a near-infrared
      fluorescent cyanine dye Cy5.5. The nanoprobe DGL-U11 has several preferable
      characteristics, such as active peptide targeting to activator receptor, good
      biocompatibility, dual-modal imaging diagnosis, and well controlled diameter in a
      range of 15-25 nm. Upon incorporation of the active U11 peptide target to the
      overexpressed activator receptor uPAR, the targeted nanoprobe DGL-U11 can
      increase to the earlier PanIN-II stage through in vivo NIRF imaging. Labeled with
      both MR and NIRF bioimaging reporters, the uPAR-targeted dual-modal nanoprobe is
      very effective in the targeted imaging of precancerous PanINs and PDAC lesions
      with high sensitivity and spatial resolution, providing a promising platform to
      the ultra-early detection of PDAC.

PMID- 29195014
TI  - Long-term penile morphometric alterations in patients treated with robot-assisted
      versus open radical prostatectomy.
AB  - Neglected side effects after radical prostatectomy have been previously reported.
      In this context, the prevalence of penile morphometric alterations has never been
      assessed in robot-assisted radical prostatectomy series. We aimed to assess
      prevalence of and predictors of penile morphometric alterations (i.e. penile
      shortening or penile morphometric deformation) at long-term follow-up in patients
      submitted to either robot-assisted (robot-assisted radical prostatectomy) or open
      radical prostatectomy. Sexually active patients after either robot-assisted
      radical prostatectomy or open radical prostatectomy prospectively completed a 28
      item questionnaire, with sensitive issues regarding sexual function, namely
      orgasmic functioning, climacturia and changes in morphometric characteristics of
      the penis. Only patients with a post-operative follow-up >= 24 months were
      included. Patients submitted to either adjuvant or salvage therapies or those who
      refused to comprehensively complete the questionnaire were excluded from the
      analyses. A propensity-score matching analysis was implemented to control for
      baseline differences between groups. Logistic regression models tested potential
      predictors of penile morphometric alterations at long-term post-operative follow
      up. Overall, 67 (50%) and 67 (50%) patients were included after open radical
      prostatectomy or robot-assisted radical prostatectomy, respectively. Self-rated
      post-operative penile shortening and penile morphometric deformation were
      reported by 75 (56%) and 29 (22.8%) patients, respectively. Rates of penile
      shortening and penile morphometric deformation were not different after open
      radical prostatectomy and robot-assisted radical prostatectomy [all p > 0.5]. At
      univariable analysis, self-reported penile morphometric alterations (either
      penile shortening or penile morphometric deformation) were significantly
      associated with baseline international index of erectile function-erectile
      function scores, body mass index, post-operative erectile function recovery, year
      of surgery and type of surgery (all p < 0.05). At multivariable analysis, robot
      assisted radical prostatectomy was independently associated with a lower risk of
      post-operative penile morphometric alterations (OR: 0.38; 95% CI: 0.16-0.93).
      Self-perceived penile morphometric alterations were reported in one of two
      patients after radical prostatectomy at long-term follow-up, with open surgery
      associated with a potential higher risk of this self-perception.

PMID- 29195016
TI  - Association of high cost sharing and targeted therapy initiation among elderly
      Medicare patients with metastatic renal cell carcinoma.
AB  - High out-of-pocket costs may limit access to oral therapies covered by patients'
      prescription drug benefits. We explored financial barriers to treatment
      initiation in patients newly diagnosed with metastatic renal cell carcinoma
      (mRCC) by comparing Medicare Part D patients with low out-of-pocket costs due to
      receipt of full low-income subsidies (LIS beneficiaries) to their counterparts
      who were responsible for more than 25% cost sharing during Medicare's initial
      coverage phase (non-LIS beneficiaries). We used 2011-2013 100% Medicare claims
      for non-LIS and LIS beneficiaries newly diagnosed with metastases in the liver,
      lung, or bone to examine targeted therapy treatment initiation rates and time to
      initiation for (1) oral medications (sorafenib, sunitinib, everolimus, pazopanib,
      or axitinib) covered under Medicare's prescription drug benefit (Part D); (2)
      injected or infused medications (temsirolimus or bevacizumab) covered by
      Medicare's medical benefit (Part B); and (3) any (Part D or Part B) targeted
      therapy. The final sample included 1721 patients. On average, non-LIS patients
      were responsible for out-of-pocket costs of >=$2,800 for their initial oral
      prescription, as compared to <=$6.60 for LIS patients. Compared to LIS patients,
      a lower percentage of non-LIS patients initiated oral therapies (risk-adjusted
      rates, 20.7% vs. 33.9%; odds ratio [OR] = 0.49, 95% CI: 0.36-0.67, P < 0.001) and
      any targeted therapies (26.7% vs. 40.4%, OR = 0.52, 95% CI: 0.38-0.71, P <
      0.001). Non-LIS patients were also slower to access therapy. High cost sharing
      was associated with reduced and/or delayed access to targeted therapies under
      Medicare Part D, suggesting that financial barriers play a role in treatment
      decisions.

PMID- 29195019
TI  - Is immunosuppression, induced by neonatal thymectomy, compatible with poor
      reproductive performance in adult male rats?
AB  - With increasing knowledge that the immune system has a major impact on
      reproductive health, the potential for cells arising in organs such as the thymus
      to alleviate oxidative stress has been revealed. This study addresses the impact
      of neonatal thymectomy on male reproductive function in pubertal and adult
      animals. Neonatal Sprague Dawley rats were allotted to four treatments consisting
      of fully thymectomized, partially thymectomized, intact, and sham-operated rats.
      Half of the rats in each treatment were sacrificed at 40 and the other half at 80
      days of age. Testicular volume, ventral prostate and spleen weight, several sperm
      attributes (concentration, motility, livability, membrane integrity, sperm
      penetration into mucus, total antioxidant capacity, mitochondrial dehydrogenase
      activity), plasma superoxide dismutase, glutathione, and testosterone level as
      well as fertility decreased in thymectomized rats. Adrenal gland weight, sperm
      malondialdehyde level, indices of oxidative stress, sperm abnormality, testicular
      and sperm lipid peroxidation, protein carbonylation, and sperm reactive oxygen
      species generation increased in thymectomized rats. In thymectomized rats, the
      testes contained high levels of malondialdehyde but low levels of glutathione and
      ferric-reducing antioxidant power. Epididymal sperm reactive oxygen species,
      blood lipid peroxidation, and oxidative stress indices in blood and spermatozoa
      were highest in fully thymectomized, intermediate in partially thymectomized, and
      lowest in both pubertal and mature control rats. Blood levels of superoxide
      dismutase, lipid peroxidation indices, and testosterone, and mitochondrial
      adenosine triphosphate and dehydrogenase activities in epididymal spermatozoa
      were lowest in fully thymectomized, intermediate in partially thymectomized, and
      highest in both pubertal and mature control rats. The data indicated that
      increased oxidative stress and mitochondrial dysfunction might play a role in the
      mechanism of immunosuppression-induced testicular and sperm abnormalities.

PMID- 29195017
TI  - High Health Care Utilization Preceding Diagnosis of Systemic Lupus Erythematosus
      in Youth.
AB  - OBJECTIVE: Childhood-onset systemic lupus erythematosus (SLE) is associated with
      high risk for organ damage, which may be mitigated by early diagnosis and
      treatment. We characterized health care utilization for youth in the year
      preceding SLE diagnosis compared to controls. METHODS: Using Clinformatics
      DataMart (OptumInsight) de-identified administrative data from 2000 to 2013, we
      identified 682 youth ages 10-24 years with new-onset SLE (>=3 International
      Classification of Diseases, Ninth Revision codes for SLE 710.0, each >30 days
      apart), and 1,364 age- and sex-matched healthy controls. We compared the
      incidence of ambulatory, emergency, and inpatient visits 12 months before SLE
      diagnosis and frequency of primary diagnoses. We examined subject characteristics
      associated with utilization preceding SLE diagnosis. RESULTS: Youth with SLE had
      significantly more visits in the year preceding diagnosis than controls across
      ambulatory (incidence rate ratio [IRR] 2.48, P < 0.001), emergency (IRR 3.42, P <
      0.001), and inpatient settings (IRR 3.02, P < 0.001). The most frequent acute
      care diagnoses and median days to SLE diagnosis were: venous thromboembolism
      (313, interquartile range [IQR] 18-356), thrombocytopenia (278, IQR 39-354),
      chest pain (73, IQR 29.5-168), fever (52, IQR 17-166), and acute kidney failure
      (14, IQR 5-168). Having a psychiatric diagnosis prior to SLE diagnosis was
      strongly associated with increased utilization across all settings. CONCLUSION:
      Youth with SLE have high health care utilization throughout the year preceding
      SLE diagnosis. Examining variable diagnostic trajectories of youth requiring
      acute care preceding SLE diagnosis, and increased attention to psychiatric
      morbidity, may help improve care for youth with new-onset SLE.

PMID- 29195013
TI  - Effect of bacterial growth rate on bacteriophage population growth rate.
AB  - It is important to understand how physiological state of the host influence
      propagation of bacteriophages (phages), due to the potential higher phage
      production needs in the future. In our study, we tried to elucidate the effect of
      bacterial growth rate on adsorption constant (delta), latent period (L), burst
      size (b), and bacteriophage population growth rate (lambda). As a model system, a
      well-studied phage T4 and Escherichia coli K-12 as a host was used. Bacteria were
      grown in a continuous culture operating at dilution rates in the range between
      0.06 and 0.98 hr-1 . It was found that the burst size increases linearly from 8
      PFU.cell-1 to 89 PFU.cell-1 with increase in bacteria growth rate. On the other
      hand, adsorption constant and latent period were both decreasing from 2.6?10-9 
      ml.min-1 and 80 min to reach limiting values of 0.5 * 10-9  ml.min-1 and 27 min
      at higher growth rates, respectively. Both trends were mathematically described
      with Michaelis-Menten based type of equation and reasons for such form are
      discussed. By applying selected equations, a mathematical equation for prediction
      of bacteriophage population growth rate as a function of dilution rate was
      derived, reaching values around 8 hr-1 at highest dilution rate. Interestingly,
      almost identical description can be obtained using much simpler Monod type
      equation and possible reasons for this finding are discussed.

PMID- 29195022
TI  - Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities.
AB  - Structured macroporous hydrogels that have controllable porosities on both the
      nanoscale and the microscale offer both the swelling and interfacial properties
      of bulk hydrogels as well as the transport properties of "hard" macroporous
      materials. While a variety of techniques such as solvent casting, freeze drying,
      gas foaming, and phase separation have been developed to fabricate structured
      macroporous hydrogels, the typically weak mechanics and isotropic pore structures
      achieved as well as the required use of solvent/additives in the preparation
      process all limit the potential applications of these materials, particularly in
      biomedical contexts. This review highlights recent developments in the field of
      structured macroporous hydrogels aiming to increase network strength, create
      anisotropy and directionality within the networks, and utilize solvent-free or
      additive-free fabrication methods. Such functional materials are well suited for
      not only biomedical applications like tissue engineering and drug delivery but
      also selective filtration, environmental sorption, and the physical templating of
      secondary networks.

PMID- 29195020
TI  - In Vivo FRET Imaging to Predict the Risk Associated with Hepatic Accumulation of
      Squalene-Based Prodrug Nanoparticles.
AB  - Forster resonance energy transfer (FRET) is used here for the first time to
      monitor the in vivo fate of nanoparticles made of the squalene-gemcitabine
      prodrug and two novel derivatives of squalene with the cyanine dyes 5.5 and 7.5,
      which behave as efficient FRET pair in the NIR region. Following intravenous
      administration, nanoparticles initially accumulate in the liver, then they show
      loss of their integrity within 2 h and clearance of the squalene bioconjugates is
      observed within 24 h. Such awareness is a key prerequisite before introduction
      into clinical settings.

PMID- 29195021
TI  - Association Between Marginal Jawbone Loss and Onset of Rheumatoid Arthritis and
      Relationship to Plasma Levels of RANKL.
AB  - OBJECTIVE: To investigate whether periodontitis, characterized by marginal
      jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to
      analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption)
      and anti-citrullinated peptide antibodies (ACPAs) in presymptomatic individuals
      compared with matched referent controls. METHODS: Marginal jawbone loss was
      measured on dental radiographs of the premolar/molar regions in the jaws in 176
      subjects, 93 of whom subsequently developed RA. Among these participating
      subjects, 46 had documented radiographs predating symptom onset, and 45 cases
      could be matched to controls, according to sex, age, and smoking status. Plasma
      RANKL concentrations were analyzed using enzyme-linked immunosorbent assay. A
      receiver operating characteristic curve was used to define the cutoff value for
      RANKL positivity. RESULTS: Bone loss was significantly greater in presymptomatic
      subjects classified as never smokers compared with that in controls, and
      increasing levels of bone loss were associated with a higher risk of the
      subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01
      1.05). No association between jawbone loss and RA was observed in smokers. A
      significantly greater extent of marginal jawbone loss was detected in RANKL
      positive presymptomatic subjects, and even more pronounced jawbone loss was
      observed in those who were positive for both RANKL and ACPA. CONCLUSION: Marginal
      jawbone loss preceded the clinical onset of RA symptoms, but this was observed
      only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in
      RANKL-positive presymptomatic subjects compared with RANKL-negative
      presymptomatic subjects and was highest in presymptomatic subjects positive for
      both ACPA and RANKL.

PMID- 29195025
TI  - Lack of additional effects of long-term, low-dose clarithromycin combined
      treatment compared with topical steroids alone for chronic rhinosinusitis in
      China: a randomized, controlled trial.
AB  - BACKGROUND: In China, clarithromycin is considered an effective treatment option
      for chronic rhinosinusitis (CRS) due to its unique immunopathologic
      characteristics. Our study's aim was to determine whether a topical steroid and
      clarithromycin combination is better than a single topical steroid for Chinese
      patients with CRS. METHODS: Patients with CRS with/without nasal polyps were
      included in this study and randomly assigned to a clarithromycin plus budesonide
      aqua nasal spray group (CLM + BUD, clarithromycin 0.25 g/d and budesonide 256
      MUg/d) or a budesonide-alone group (BUD, budesonide 256 MUg/d). The treatment
      period was 3 months. The primary outcome was visual analog scale (VAS) score for
      5 major symptoms and a general nasal symptom. Other assessments included the 22
      item Sino-Nasal Outcome Test (SNOT-22), computed tomography scan (Lund-Mackay
      score), and rigid nasal endoscopy (Lund-Kennedy score). Nasal secretion
      evaluation was the secondary outcome. RESULTS: Seventy-four patients were
      included and randomly assigned to the CLM + BUD group (n = 38) or the BUD group
      (n = 36). VAS scores for nasal obstruction, rhinorrhea, smell reduction,
      headache, nasal pain, and general nasal symptom were markedly improved in both
      treatment arms, but the differences between groups were not significant.
      Furthermore, SNOT-22, Lund-Mackay, and Lund-Kennedy scores improved significantly
      after treatment in both groups, and were slightly better in the CLM + BUD group.
      For the responders in the CLM + BUD group, interleukin (IL)-6 and IL-8 were
      markedly reduced. CONCLUSION: The combination of CLM + BUD for the treatment of
      first-time-diagnosed CRS in this Chinese population cohort did not show a better
      effect compared with a single BUD regimen, but it may have a better effect in
      some patients with increased IL-6 or IL-8.

PMID- 29195027
TI  - Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging:
      Structural Requirements for Improved in vivo Stability in Tracer Design.
AB  - Diagnosis and localization of bacterial infections remains a significant clinical
      challenge. Harnessing bacteria-specific metabolic pathways, such as the
      maltodextrin transport mechanism, may allow specific localization and imaging of
      small or hidden colonies. This requires that the intrabacterial tracer
      accumulation provided by the transporter is matched by high serum stability of
      the tracer molecule. Herein, radiolabeled maltodextrins of varying chain lengths
      and with free nonreducing/reducing ends are reported and their behavior against
      starch-degrading enzymes in the blood, which compromise their serum stability, is
      evaluated. Successful single-photon emission computed tomography (SPECT) imaging
      is shown in a footpad infection model in vivo by using the newly developed model
      tracer, [99m Tc]MB1143, and the signal is compared with that of 18 F
      fluorodeoxyglucose positron emission tomography ([18 F]FDG-PET) as a nonbacterial
      specific marker for inflammation. Although the [99m Tc]MB1143 imaging signal is
      highly specific, it is low, most probably due to insufficient serum stability of
      the tracer. A series of stability tests with different 18 F-labeled maltodextrins
      finally yielded clear structural guidelines regarding substitution patterns and
      chain lengths of maltodextrin-based tracers for nuclear imaging of bacterial
      infections.

PMID- 29195026
TI  - Effects of the insulin-like growth factor system on testicular differentiation
      and function: a review of the literature.
AB  - We recently described the occurrence of cryptorchidism,
      oligoasthenoteratozoospermia, and genital abnormalities in patients with distal
      15q chromosome structural abnormalities. This observation brought us to
      hypothesize that insulin-like growth factor (IGF) receptor (IGF1R), mapping on
      the 15q 26.3 chromosomal band, may be involved in testicular function. To further
      evaluate this topic, we reviewed in vitro and in vivo studies exploring the role
      of the IGF system [IGF1, IGF2, IGF1R, insulin receptor substrates (IRS)] at the
      testicular level both in animals and in humans. In animals, IGF1/IGF1R has been
      found to be involved in testicular development during embryogenesis, in Sertoli
      cell (SC) proliferation, and in germ cell (GS) proliferation and differentiation.
      Interestingly, IGF1R seems to mediate follicle-stimulating hormone (FSH) effects
      through the PI3K/AKT pathway. In humans, IGF1 directly increases testicular
      volume. The molecular pathways responsible for testicular differentiation and
      IGF1/IGF1R signaling are highly conserved among species; therefore, the IGF
      system may be involved in FSH signaling also in humans. We suggest a possible
      molecular pathway occurring in human SCs, which involves both IGF1 and FSH
      through the PI3K/AKT pathway. The acknowledgment of an IGF1 mediation of the FSH
      induced effects may open new ways for a targeted therapy in idiopathic non-FSH
      responder oligoasthenoteratozoospermia.

PMID- 29195031
TI  - Surgical correction of Peyronie's disease via tunica albuginea plication: long
      term follow-up.
AB  - Peyronie's disease (PD) is an acquired connective tissue disorder of the tunica
      albuginea with fibrosis and inflammation that lead to palpable plaques formation,
      penile curvature, and pain during erection. Patients report negative effects on
      main domains such as physical appearance and self-image, sexual function, and
      performance. The aim of this study was to evaluate plication of the albuginea
      outcomes after a long-term follow-up period. Between 1998 and 2006, a total of
      204 patients with PD underwent surgical correction with albuginea plication
      technique. We obtained complete long-term follow-up data in 187 cases. The follow
      up data included evaluation of curvature correction, penile shortening, sexual
      function, complications, and patient satisfaction. After a mean follow-up of 141
      months, the most common postoperative complications were: loss of length (150
      patients had a minimal penile shortening <=1.5 cm, 37 patient between 1.5, and 3
      cm, none >3 cm), recurrent or residual penile curvature (15 patients, without
      impairing sexual intercourse), erectile dysfunction (15 patients had IIEF-5 < 10
      at 5 years of follow-up vs. 28 patients at 10 years), change in penile sensation
      (37 patients experienced paresthesia of the glans 1 year after surgery, 28 at 5
      years, and 15 at 10 years); painful or palpable suture knots (in 20 cases)
      spontaneously healed in 3 months. Overall, 77% of the patients and partners were
      completely satisfied, 14% partially satisfied, and 9% unsatisfied. Plication
      procedure is safe and simple to be performed compared with the classical Nesbit's
      procedure. It has a shorter surgical time, lower costs, and could be successfully
      performed by less experienced surgeons too. It has a minimal risk of de novo
      erectile dysfunction, injury to the dorsal neurovascular bundle. Results are good
      in terms of patient satisfaction according to anatomical outcome and functional
      correction.

PMID- 29195030
TI  - Accuracy of birth certificate head circumference measurements: Massachusetts,
      2012-2013.
AB  - BACKGROUND: Zika virus has recently emerged as a novel cause of microcephaly. CDC
      has asked states to rapidly ascertain and report cases of Zika-linked birth
      defects, including microcephaly. Massachusetts added head circumference to its
      birth certificate (BC) in 2011. The accuracy of head circumference measurements
      from state vital records data has not been reported. METHODS: We sought to assess
      the accuracy of Massachusetts BC head circumference measurements by comparing
      them to measurements for 2,217 infants born during 2012-2013 captured in the
      Massachusetts Birth Defects Monitoring Program (BDMP) data system. BDMP contains
      information abstracted directly from infant medical records and served as the
      true head circumference value (i.e., gold standard) for analysis. We calculated
      the proportion of head circumference measurements in agreement between the BC and
      BDMP data. We assigned growth chart head circumference percentile categories to
      each BC and BDMP measurement, and calculated the sensitivity and specificity of
      BC-based categories to predict BDMP-based categories. RESULTS: No difference was
      found in head circumference measurements between the two sources in 77.9% (n =
      1,727) of study infants. The sensitivity of BC-based head circumference
      percentile categories ranged from 85.6% (<3rd percentile) to 92.7% (>=90th
      percentile) and the specificity ranged from 97.6% (>=90th percentile) to 99.3%
      (<3rd percentile). CONCLUSIONS: BC head circumference measurements agreed with
      those abstracted from the medical chart the majority of the time. Head
      circumference measurements on the BC were more specific than sensitive across all
      standardized growth chart percentile categories.

PMID- 29195035
TI  - Obstructive Sleep Apnea as a Complication of Bipolar Disorder and Its Treatment:
      A Review and Approach to Management.

PMID- 29195033
TI  - Total prevention of folic acid-preventable spina bifida and anencephaly would
      reduce child mortality in India: Implications in achieving Target 3.2 of the
      Sustainable Development Goals.
AB  - BACKGROUND: The potential to reduce child mortality by preventing folic acid
      preventable spina bifida and anencephaly (FAP SBA) is inadequately appreciated.
      To quantify possible reduction in FAP SBA-associated child mortality in low- and
      middle-income countries, we conducted an analysis to demonstrate in India, a
      country with more than 25 million births and 1.2 million under-five deaths each
      year, the decrease in neonatal, infant, and under-five mortality that would occur
      through total prevention of FAP SBA. METHODS: We estimated the percent reductions
      in neonatal, infant, and under-five mortality that would have occurred in India
      in 2015 had all of FAP SBA been prevented. We also estimated the contributions of
      these reductions toward India's Sustainable Development Goals on child mortality
      indicators. We considered the overall prevalence of spina bifida and anencephaly
      in India as 5 per 1,000 live births, of which 90% were preventable with effective
      folic acid intervention. RESULTS: In the year 2015, folic acid interventions
      would have prevented about 116,070 cases of FAP SBA and 101,565 under-five deaths
      associated with FAP SBA. Prevention of FAP SBA would have reduced annually,
      neonatal, infant, and under-five mortality by 10.2%, 8.9%, and 8.3%,
      respectively. These reductions would have contributed 18.5% and 17.2% to the
      reductions in neonatal and under-five mortality, respectively, needed by India to
      achieve its 2030 Sustainable Developmental Goal Target 3.2 addressing preventable
      child mortality. CONCLUSIONS: Total prevention of FAP SBA clearly has a
      significant potential for immediate reductions in neonatal, infant, and under
      five mortality in India, and similarly other countries.

PMID- 29195024
TI  - Tuberculosis Risk in Ankylosing Spondylitis, Other Spondyloarthritis, and
      Psoriatic Arthritis in Sweden: A Population-Based Cohort Study.
AB  - OBJECTIVE: Rheumatoid arthritis is a risk factor for tuberculosis (TB),
      particularly following treatment with biologic agents. Since these therapies are
      increasingly used in ankylosing spondylitis (AS), other types of
      spondyloarthritis (SpA), and psoriatic arthritis (PsA), we investigated the
      corresponding TB risks in these patients. METHODS: We identified individuals with
      AS/SpA/PsA, and non-AS/SpA/PsA comparators by linking Swedish national patient,
      population, TB, and rheumatology registers, and followed them for TB occurrence.
      Incidence rates were estimated for biologic-naive and biologic-exposed patients
      and the comparators. We calculated hazard ratios (HRs), adjusted for age, sex,
      and country of birth. RESULTS: Included in this study were 38,702 patients with
      AS/SpA/PsA, and 200,417 persons from the general population. Among the patients,
      11 active TB cases were identified, with an incidence rate (per 105 ) of 22 (95%
      confidence interval [95% CI] 8.3-59.2) for biologic-exposed patients, 2.7 (95% CI
      1.3-5.6) for biologic-naive patients, and 2.4 (95% CI 1.8-3.3) for non-AS/SpA/PsA
      comparators. The adjusted HR comparing biologic-naive patients to the general
      population was 1.2 (95% CI 0.5-2.7), and 7.5 (95% CI 1.9-29) comparing biologic
      exposed to biologic-naive patients. CONCLUSION: Biologic-naive AS/SpA/PsA
      patients are not at an increased TB risk in Sweden. Following treatment with
      biologic agents, the risk increased, but the absolute TB risk was low.

PMID- 29195032
TI  - Ultrasensitive NIR-SERRS Probes with Multiplexed Ratiometric Quantification for
      In Vivo Antibody Leads Validation.
AB  - Immunotargeting ability of antibodies may show significant difference between in
      vitro and in vivo. To select antibody leads with high affinity and specificity,
      it is necessary to perform in vivo validation of antibody candidates following in
      vitro antibody screening. Herein, a robust in vivo validation of anti-tetraspanin
      8 antibody candidates against human colon cancer using ratiometric quantification
      method is reported. The validation is performed on a single mouse and analyzed by
      multiplexed surface-enhanced Raman scattering using ultrasensitive and near
      infrared (NIR)-active surface-enhanced resonance Raman scattering nanoprobes (NIR
      SERRS dots). The NIR-SERRS dots are composed of NIR-active labels and Au/Ag
      hollow-shell assembled silica nanospheres. A 93% of NIR-SERRS dots is detectable
      at a single-particle level and signal intensity is 100-fold stronger than that
      from nonresonant molecule-labeled spherical Au NPs (80 nm). The result of SERRS
      based antibody validation is comparable to that of the conventional method using
      single-photon-emission computed tomography. The NIR-SERRS-based strategy is an
      alternate validation method which provides cost-effective and accurate
      multiplexing measurements for antibody-based drug development.

PMID- 29195028
TI  - Effect of varicocelectomy and/or mast cells stabilizer on sperm DNA fragmentation
      in infertile patients with varicocele.
AB  - This study aimed to assess the effect of varicocelectomy and/or mast cells (MCs)
      stabilizer on sperm DNA fragmentation in infertile men with varicocele (Vx).
      Overall, 120 infertile patients were randomized to three equal treatment arms;
      patients that underwent varicocelectomy, patients on 1 mg ketotifen twice daily
      for three months, and patients that underwent varicocelectomy followed with 1 mg
      ketotifen twice daily for three months. These patients were subjected to history
      taking, clinical examination, semen analysis, and estimation of sperm DNA
      fragmentation index (DFI). After 3 months, all investigated groups showed
      significant improvement regarding the mean total sperm count, sperm
      concentration, total sperm motility, and sperm normal forms percentage compared
      with the pre-treatment data. As well, the mean sperm DFI was significantly
      improved compared with the pre-treatment data; in men that underwent
      varicocelectomy (34.6% vs. 28.3%), in men on MC stabilizer only (33.4% vs.
      27.8%), and in men that underwent varicocelectomy followed by MC stabilizer
      (34.3% vs. 25.1%). Sperm DFI improvement percentages showed the highest
      improvement in men that underwent varicocelectomy followed with MC stabilizer
      compared with the other two groups (26.8% vs. 18.2%, 16.8%). Sperm DFI
      improvement percentages showed significant increases in the infertile patients
      with Vx grade III compared to Vx grade II in all investigated groups. It is
      concluded that in infertile men associated with Vx and high sperm DFI, surgical
      repair followed with MCs stabilizer significantly improve sperm DFI compared with
      either surgical repair or MCs stabilizer alone.

PMID- 29195029
TI  - Association of MGMT promoter methylation with tumorigenesis features in patients
      with ovarian cancer: A systematic meta-analysis.
AB  - BACKGROUND: The MGMT is a key tumor suppressor gene and aberrant promoter
      methylation has been reported in many cancers. However, the relationship between
      MGMT promoter methylation and ovarian cancer remains controversial. This meta
      analysis was first conducted to estimate the clinical significance of MGMT
      promoter methylation in ovarian carcinoma. METHODS: Literature search was
      performed in the PubMed, Embase, EBSCO and Cochrane Library databases. The pooled
      odds ratio (OR) and their corresponding 95% confidence interval (95% CI) were
      summarized. RESULTS: Final 10 studies with 910 ovarian tissue samples were
      included in this meta-analysis. MGMT promoter methylation was significantly
      higher in ovarian cancer than in normal ovarian tissues (OR = 4.13, 95% CI = 2.32
      7.33, p < .001). The MGMT had a similar methylation status in cancer versus
      benign lesions and low malignant potential (LMP) samples (OR = 2.01, 95% CI =
      0.67-6.04, p = .212; OR = 1.42, 95% CI = 0.46-4.40, p = .543; respectively). MGMT
      promoter methylation was correlated with pathological types in which it was
      significantly lower in serous cancer than in nonserous cancer (OR = 0.29, 95% CI
      = 0.14-0.59, p = .001). The methylation of the MGMT promoter was not associated
      with clinical stage and tumor grade (OR = 1.46, 95% CI = 0.71-3.02, p = .301; OR
      = 1.13, 95% CI = 0.51-2.46, p = .767; respectively). CONCLUSIONS: MGMT promoter
      methylation may be correlated with the tumorigenesis of ovarian cancer. It was
      associated with tumor histotypes, but not correlated with clinical stage and
      tumor grade. More prospective studies with lager sample sizes are necessary in
      the future.

PMID- 29195034
TI  - Birth defect survival for Hispanic subgroups.
AB  - BACKGROUND: Previous studies demonstrate that infant and childhood mortality
      differ among children with birth defects by maternal race/ethnicity, but limited
      mortality information is published for Hispanic ethnic subgroups. METHODS: We
      performed a retrospective cohort study using data for children with birth defects
      born to Hispanic mothers during 1999-2007 from 12 population-based state birth
      defects surveillance programs. Deaths were ascertained through multiple sources.
      Survival probabilities were estimated by the Kaplan-Meier method. Cox
      proportional hazards regression was used to examine the effect of clinical and
      demographic factors on mortality risk. RESULTS: Among 28,497 Hispanic infants and
      children with major birth defects, 1-year survival was highest for infants born
      to Cuban mothers at 94.6% (95% confidence intervals [CI] 92.7-96.0) and the
      lowest for Mexicans at 90.2% (95% CI 89.7-90.6; p < .0001). For children aged up
      to 8 years, survival remained highest for Cuban Americans at 94.1% (95% CI 91.8
      95.7) and lowest for Mexican Americans at 89.2% (95% CI 88.7-89.7; p = .0002). In
      the multivariable analysis using non-Hispanic White as the reference group, only
      infants and children born to Mexican mothers were noted to have a higher risk of
      mortality for cardiovascular defects. CONCLUSIONS: This analysis provides a
      better understanding of survival and mortality for Hispanic infants and children
      with selected birth defects. The differences found in survival, particularly the
      highest survival rates for Cuban American children and lowest for Mexican
      American children with birth defects, underscores the importance of assessing
      Hispanic ethnic subgroups, as differences among subgroups appear to exist.

PMID- 29195036
TI  - Neuroleptic Malignant Syndrome After Early Administration of Risperidone Long
      Acting Injection.

PMID- 29195040
TI  - Correction to Fragment-Based Identification of Influenza Endonuclease Inhibitors.

PMID- 29195038
TI  - Well-Defined Cationic N-[3-(Dimethylamino)propyl]methacrylamide Hydrochloride
      Based (Co)polymers for siRNA Delivery.
AB  - Cationic glycopolymers have shown to be excellent candidates for the fabrication
      of gene delivery devices due to their ability to electrostatically interact with
      negatively charged nucleic acids and the carbohydrate residues ensure enhanced
      stability and low toxicity of the polyplexes. The ability to engineer the
      polymers for optimized compositions, molecular weights, and architectures is
      critical in the design of effective gene delivery vehicles. Therefore, in this
      study, the aqueous reversible addition-fragmentation chain transfer
      polymerization (RAFT) was used to synthesize well-defined cationic glycopolymers
      with various cationic segments. For the preparation of cationic parts, N-[3
      (dimethylamino)propyl]methacrylamide hydrochloride (DMAPMA.HCl), water-soluble
      methacrylamide monomer containing tertiary amine, was polymerized to produce
      DMAPMA.HCl homopolymer, which was then used as macroCTA in the block
      copolymerization with two other methacrylamide monomers containing different
      pendant groups, namely, 2-aminoethyl methacrylamide hydrochloride (AEMA) (with
      primary amine) and N-(3-aminopropyl) morpholine methacrylamide (MPMA) (with
      morpholine ring). In addition, statistical copolymers of DMAPMA.HCl with either
      AEMA or MPMA were also synthesized. All resulting cationic polymers were utilized
      as macroCTA for the RAFT copolymerization with 2-lactobionamidoethyl
      methacrylamide (LAEMA), which consists of the pendent galactose residues to
      achieve DMAPMA.HCl-based glycopolymers. From the in vitro cytotoxicity study, the
      cationic glycopolymers showed better cell viabilities than the corresponding
      cationic homopolymers. Furthermore, complexation of the cationic polymers with
      siRNA, cellular uptake of the resulting polyplexes, and gene knockdown
      efficiencies were evaluated. All cationic polymers/glycopolymers demonstrated
      good complexation ability with siRNA at low weight ratios. Among these cationic
      polymer-siRNA polyplexes, the polyplexes prepared from the two glycopolymers,
      P(DMAPMA65-b-LAEMA15) and P[(DMAPMA65-b-MPMA63)-b-LAEMA16], showed outstanding
      results in the cellular uptake, high EGFR knockdown, and low post-transfection
      toxicity, suggesting the great potential in siRNA delivery of these novel
      glycopolymers.

PMID- 29195023
TI  - Computational modeling of single-cell mechanics and cytoskeletal mechanobiology.
AB  - Cellular cytoskeletal mechanics plays a major role in many aspects of human
      health from organ development to wound healing, tissue homeostasis and cancer
      metastasis. We summarize the state-of-the-art techniques for mathematically
      modeling cellular stiffness and mechanics and the cytoskeletal components and
      factors that regulate them. We highlight key experiments that have assisted model
      parameterization and compare the advantages of different models that have been
      used to recapitulate these experiments. An overview of feed-forward mechanisms
      from signaling to cytoskeleton remodeling is provided, followed by a discussion
      of the rapidly growing niche of encapsulating feedback mechanisms from
      cytoskeletal and cell mechanics to signaling. We discuss broad areas of
      advancement that could accelerate research and understanding of cellular
      mechanobiology. A precise understanding of the molecular mechanisms that affect
      cell and tissue mechanics and function will underpin innovations in medical
      device technologies of the future. WIREs Syst Biol Med 2018, 10:e1407. doi:
      10.1002/wsbm.1407 This article is categorized under: Models of Systems Properties
      and Processes > Mechanistic Models Physiology > Mammalian Physiology in Health
      and Disease Models of Systems Properties and Processes > Cellular Models.

PMID- 29195039
TI  - Variability of Greenhouse Gas Footprints of Field Tomatoes Grown for Processing:
      Interyear and Intercountry Assessment.
AB  - Our study provides an integrated analysis of the variability of greenhouse gas
      (GHG) footprints of field-grown tomatoes for processing. The global farm-specific
      data set of 890 observations across 14 countries over a three-year period (2013
      2015) was obtained from farms grown under Unilever's sustainable agricultural
      code. It represents on average 3% of the annual global production of processing
      tomatoes: insights can be used to help inform corporate sourcing strategies and
      certification schemes. The median GHG footprint ranged from 18 in Chile to 61 kg
      CO2-equiv per tonne of tomatoes in India, lower than results reported in other
      studies. We found that footprints are more consistent within countries than
      between them. Using linear mixed effect models, we quantified the relative
      influence of environmental conditions and farm management factors. Key variables
      were area of production and the method of fertilizer application. GHG footprints
      decreased with increasing area of production to a threshold of 17.4 ha. Farms
      using single fertilizer application methods in general had a larger GHG footprint
      than those using a combination of methods. We conclude that farm management
      factors should be prioritized for future data collection, and more stringent
      guidance on acceptable practices is required if greater comparability of outcomes
      is needed either within a scheme, such as the Unilever's sustainable agriculture
      code, or between schemes.

PMID- 29195042
TI  - pH Switchable Nanoassembly for Imaging a Broad Range of Malignant Tumors.
AB  - Polymer-based fluorescent nanomaterials have proven to universally image various
      tumors based on their extremely sharp responsiveness to pH change. Such a
      property has never been realized in supramolecular systems. We herein design a
      small molecule (DPP-thiophene-4) that is composed of a diketopyrrolopyrrole (DPP)
      core and two alkyl chains terminated with quaternary ammonium. DPP-thiophene-4
      can self-assemble into a nonfluorescent nanoassembly when the pH is >7.0 but
      reversibly disassembles back to fluorescent monomers when the pH is <6.8.
      Meanwhile, its fluorescence emission increases by 10-fold within a 0.2 pH unit
      change. Such a fluorogenic nanoassembly can precisely differentiate a number of
      malignant tumors among normal tissues in vivo due to the slight acidity within
      tumor microenvironments. Further the nanoassembly shows satisfactory
      biocompatibility and an effective clearance from the body. Overall, this
      supramolecular fluorogenic nanoassembly exhibits an immense potential for
      realizing broad range tumor diagnosis.

PMID- 29195041
TI  - Direct Asymmetric Ruthenium-Catalyzed Reductive Amination of Alkyl-Aryl Ketones
      with Ammonia and Hydrogen.
AB  - The asymmetric ruthenium-catalyzed reductive amination employing ammonia and
      hydrogen to primary amines is described. Here we demonstrate the capability of
      our catalyst to perform a chemo- and enantioselective process while using simple
      ammonia gas as a reagent, one of the most attractive and industrially relevant
      nitrogen sources. The presence of a catalytic amount of ammonium iodide was
      essential for obtaining good yields and enantioselectivities. The mechanism of
      this reaction was investigated by DFT and we found a viable pathway that also
      explains the trend and magnitude of enantioselectivity through the halide series
      in good agreement with the experimental data. The in-depth investigation of
      substrate conformers during the reaction turned out to be crucial in obtaining an
      accurate prediction of the enantioselectivity. Furthermore, we report the
      crystallographic data of the chiral [Ru(I)H(CO)((S,S)-f-binaphane)(PPh3)]
      complex, which we identified as the most efficient catalyst in our investigation.

PMID- 29195044
TI  - Biomimetic Oxygen-Evolving Photobacteria Based on Amino Acid and Porphyrin
      Hierarchical Self-Organization.
AB  - Biomimetic organization provides a promising strategy to develop functional
      materials and understand biological processes. However, how to mimic complex
      biological systems using simple biomolecular units remains a great challenge.
      Herein, we design and fabricate a biomimetic cyanobacteria model based on self
      integration of small bioinspired molecules, including amphiphilic amino acid, 3,4
      dihydroxyphenylalanine (DOPA), and metalloporphyrin and cobalt oxide
      nanoparticles (Co3O4 NPs), with the assistance of chemical conjugation and
      molecular self-assembly. The assembled amino acid fiber can be modified by DOPA
      to form covalently bound DOPA melanin containing hydroxyl and quinone species via
      Schiff base reaction. The adhering template can further tune the self-assembly of
      metalloporphyrin and Co3O4 NPs into J-aggregation and dispersive distribution,
      respectively, mainly via coordination binding. Metalloporphyrin molecules in the
      resulting hybrid fibers capture light; quinone species accept the excited
      electrons, and Co3O4 NPs catalyze water oxidation. Thus, the essential components
      of the photosystem-II protein complex in cyanobacteria are simplified and
      engineered into a simple framework, still retaining a similar photosynthetic
      mechanism. In addition, this architecture leads to efficient coupling of antenna,
      quinone-type reaction center, and photocatalyst, which increases the flux of
      light energy from antenna to reaction center for charge separation, resulting in
      enhanced oxygen evolution rate with excellent sustainability.

PMID- 29195047
TI  - Fluorescence Enhancement of Terminal Amine Assembled on Gold Nanoclusters and Its
      Application to Ratiometric Lysine Detection.
AB  - Ratiometric fluorescent sensors have emerged as an attractive tool for analytical
      sensing and optical imaging due to their providing a built-in self-calibration
      for environmental effects. However, cumbersome processes of nanoparticles
      modified with fluorophores for constructing traditional ratiometric sensors limit
      their further application. Herein, we report a facile and label-free strategy for
      constructing a ratiometric sensor based on an aggregation-induced-emission (AIE)
      active amine-terminated small molecule on the surface of gold nanoclusters
      (AuNCs). Intrinsic fluorescence of the terminal primary amine of the small
      molecule lysine resulting from AIE was first observed in the presence of
      glutathione-stabilized gold nanoclusters (GSH-AuNCs). Using lysine as both the
      fluorophore and the analyte, the synthesized GSH-AuNCs showed a good lysine
      responsive ratiometric property. The AIE-active dual-emitting fluorescence
      property of the GSH-AuNCs/lysine complex made it feasible to achieve
      ratiometrically detection of the analyte without conjugated fluorogen. This AIE
      active GSH-AuNC-based biosensor possesses high selectivity, rapid response, and
      excellent photostability. Moreover, the strategy opens a new pathway for the
      construction of a label-free ratiometric fluorescent sensor with various
      applications.

PMID- 29195043
TI  - Grotthuss Transport of Iodide in EMIM/I3 Ionic Crystal.
AB  - Highly ionic environments can mediate unusual chemical reactions that would
      otherwise be considered impossible based on chemical intuition. For example, the
      formation of a chemical bond between two iodide anions to form a divalent
      polyiodide anion is seemingly prohibited due to Coulombic repulsion. Using ab
      initio molecular dynamics simulations, we show that in the 1-ethyl-3
      methylimidazolium (EMIM)/I3 ionic crystal, the reactive formation of divalent and
      even trivalent polyiodide anions occurs with extremely small energetic barriers,
      due to the electrostatic field of the ionic lattice. A practical consequence of
      this anomalous reactivity is that iodide anions are efficiently transported
      within the crystal through a "Grotthuss-exchange" mechanism involving bond
      breaking and forming events. We characterize two distinct transport pathways,
      involving both I42- and I73- intermediates, with fast transport of iodide
      resulting from the release of an I- anion on the opposite side of the
      intermediate species from the initial bond formation. The ordered cation
      arrangement in the crystal provides the necessary electrostatic screening for
      close approach of anions, suggesting a new counterintuitive approach to obtain
      high ionic conductivity. This new design principle could be used to develop
      better solid-state electrolytes for batteries, fuel cells, and supercapacitors.

PMID- 29195037
TI  - Intrabilayer 64Cu Labeling of Photoactivatable, Doxorubicin-Loaded Stealth
      Liposomes.
AB  - Doxorubicin (Dox)-loaded stealth liposomes (similar to those in clinical use) can
      incorporate small amounts of porphyrin-phospholipid (PoP) to enable
      chemophototherapy (CPT). PoP is also an intrinsic and intrabilayer 64Cu chelator,
      although how radiolabeling impacts drug delivery has not yet been assessed. Here,
      we show that 64Cu can radiolabel the stable bilayer of preformed Dox-loaded PoP
      liposomes with inclusion of 1% ethanol without inducing drug leakage. Dox-PoP
      liposomes labeled with intrabilayer copper behaved nearly identically to
      unlabeled ones in vitro and in vivo with respect to physical parameters,
      pharmacokinetics, and CPT efficacy. Positron emission tomography and near
      infrared fluorescence imaging visualized orthotopic mammary tumors in mice with
      passive liposome accumulation following administration. A single CPT treatment
      with 665 nm light (200 J/cm2) strongly inhibited primary tumor growth. Liposomes
      accumulated in lung metastases, based on NIR imaging. These results establish the
      feasibility of CPT interventions guided by intrinsic multimodal imaging of Dox
      loaded stealth PoP liposomes.

PMID- 29195045
TI  - Divergent Spatiotemporal Interaction of Angiotensin Receptor Blocking Drugs with
      Angiotensin Type 1 Receptor.
AB  - Crystal structures of the human angiotensin II type 1 receptor (AT1R) complex
      with the antihypertensive agent ZD7155 (PDB id: 4YAY ) and the blood pressure
      medication Benicar (PDB id: 4ZUD ) showed that binding poses of both antagonists
      are similar. This finding implies that clinically used angiotensin receptor
      blocking (ARB) drugs may interact in a similar fashion. However, clinically
      observed differences in pharmacological and therapeutic efficacies of ARBs lead
      to the question of whether the dynamic interactions of AT1R with ARBs vary. To
      address this, we performed induced-fit docking (IFD) of eight clinically used
      ARBs to AT1R followed by 200 ns molecular dynamic (MD) simulation. The
      experimental Ki values for ARBs correlated remarkably well with calculated free
      energy with R2 = 0.95 and 0.70 for AT1R-ARB models generated respectively by IFD
      and MD simulation. The eight ARB-AT1R complexes share a common set of binding
      residues. In addition, MD simulation results validated by mutagenesis data
      discovered distinctive spatiotemporal interactions that display unique bonding
      between an individual ARB and AT1R. These findings provide a reasonably broader
      picture reconciling the structure-based observations with clinical studies
      reporting efficacy variations for ARBs. The unique differences unraveled for ARBs
      in this study will be useful for structure-based design of the next generation of
      more potent and selective ARBs.

PMID- 29195046
TI  - Rapid Ordering in "Wet Brush" Block Copolymer/Homopolymer Ternary Blends.
AB  - The ubiquitous presence of thermodynamically unfavored but kinetically trapped
      topological defects in nanopatterns formed via self-assembly of block copolymer
      thin films may prevent their use for many envisioned applications. Here, we
      demonstrate that lamellae patterns formed by symmetric polystyrene-block
      poly(methyl methacrylate) diblock copolymers self-assemble and order extremely
      rapidly when the diblock copolymers are blended with low molecular weight
      homopolymers of the constituent blocks. Being in the "wet brush" regime, the
      homopolymers uniformly distribute within their respective self-assembled
      microdomains, preventing increases in domain widths. An order-of-magnitude
      increase in topological grain size in blends over the neat (unblended) diblock
      copolymer is achieved within minutes of thermal annealing as a result of the
      significantly higher power law exponent for ordering kinetics in the blends.
      Moreover, the blends are demonstrated to be capable of rapid and robust domain
      alignment within micrometer-scale trenches, in contrast to the corresponding neat
      diblock copolymer. These results can be attributed to the lowering of energy
      barriers associated with domain boundaries by bringing the system closer to an
      order-disorder transition through low molecular weight homopolymer blending.

PMID- 29195054
TI  - Bacterial Mechanosensors.
AB  - Bacteria represent one of the most evolutionarily successful groups of organisms
      to inhabit Earth. Their world is awash with mechanical cues, probably the most
      ancient form of which are osmotic forces. As a result, they have developed highly
      robust mechanosensors in the form of bacterial mechanosensitive (MS) channels.
      These channels are essential in osmoregulation, and in this setting, provide one
      of the simplest paradigms for the study of mechanosensory transduction. We
      explore the past, present, and future of bacterial MS channels, including the
      alternate mechanosensory roles that they may play in complex microbial
      communities. Central to all of these functions is their ability to change
      conformation in response to mechanical stimuli. We discuss their gating according
      to the force-from-lipids principle and its applicability to eukaryotic MS
      channels. This includes the new paradigms emerging for bilayer-mediated channel
      mechanosensitivity and how this molecular detail may provide advances in both
      industry and medicine.

PMID- 29195049
TI  - A Solid-State Conceptualization of Information Transfer from Gene to Message to
      Protein.
AB  - In this review, we describe speculative ideas and early stage research concerning
      the flow of genetic information from the nuclear residence of genes to the
      disparate, cytoplasmic sites of protein synthesis. We propose that this process
      of information transfer is meticulously guided by transient structures formed
      from protein segments of low sequence complexity/intrinsic disorder. These low
      complexity domains are ubiquitously associated with regulatory proteins that
      control gene expression and RNA biogenesis, but they are also found in the
      central channel of nuclear pores, the nexus points of intermediate filament
      assembly, and the locations of action of other well-studied cellular proteins and
      pathways. Upon being organized into localized cellular positions via mechanisms
      utilizing properly folded protein domains, thereby facilitating elevated local
      concentration, certain low complexity domains adopt cross-beta interactions that
      are both structurally specific and labile to disassembly. These weakly tethered
      assemblies, we propose, are built to relay the passage of genetic information
      from one site to another within a cell, ensuring that the process is of extreme
      fidelity.

PMID- 29195050
TI  - Resilience of the Oral Microbiota in Health: Mechanisms That Prevent Dysbiosis.
AB  - Dental diseases are now viewed as a consequence of a deleterious shift in the
      balance of the normally stable resident oral microbiome. It is known that
      frequent carbohydrate consumption or reduced saliva flow can lead to caries, and
      excessive plaque accumulation increases the risk of periodontal diseases.
      However, when these "disease drivers" are present, while some individuals appear
      to be susceptible, others are more tolerant or resilient to suffering from
      undesirable changes in their oral microbiome. Health-maintaining mechanisms that
      limit the effect of disease drivers include the complex set of metabolic and
      functional interrelationships that develop within dental biofilms and between
      biofilms and the host. In contrast, "positive feedback loops" can develop within
      these microbial communities that disrupt resilience and provoke a large and
      abrupt change in function and structure of the ecosystem (a microbial "regime
      shift"), which promotes dysbiosis and oral disease. For instance, acidification
      due to carbohydrate fermentation or inflammation in response to accumulated
      plaque select for a cariogenic or periopathogenic microbiota, respectively, in a
      chain of self-reinforcing events. Conversely, in tolerant individuals, health
      maintaining mechanisms, including negative feedback to the drivers, can maintain
      resilience and promote resistance to and recovery from disease drivers. Recently
      studied health-maintaining mechanisms include ammonia production, limiting a drop
      in pH that can lead to caries, and denitrification, which could inhibit several
      stages of disease-associated positive feedback loops. Omics studies comparing the
      microbiome of, and its interaction with, susceptible and tolerant hosts can
      detect markers of resilience. The neutralization or inhibition of disease
      drivers, together with the identification and promotion of health-promoting
      species and functions, for example, by pre- and probiotics, could enhance
      microbiome resilience and lead to new strategies to prevent disease.

PMID- 29195055
TI  - Neuromuscular Junction Formation, Aging, and Disorders.
AB  - Synapses, the fundamental unit in neuronal circuits, are critical for learning
      and memory, perception, thinking, and reaction. The neuromuscular junction (NMJ)
      is a synapse formed between motoneurons and skeletal muscle fibers that is
      covered by Schwann cells (SCs). It is essential for controlling muscle
      contraction. NMJ formation requires intimate interactions among motoneurons,
      muscles, and SCs. Deficits in NMJ formation and maintenance cause neuromuscular
      disorders, including congenital myasthenic syndrome and myasthenia gravis. NMJ
      decline occurs in aged animals and may appear before clinical presentation of
      motoneuron disorders such as amyotrophic lateral sclerosis. We review recent
      findings in NMJ formation, maintenance, neuromuscular disorders, and aging of the
      NMJ, focusing on communications among motoneurons, muscles and SCs, and
      underlying mechanisms.

PMID- 29195056
TI  - RNA Interference-Mediated Gene Silencing by Branched Tripodal RNAs Does Not
      Require Dicer Processing.
AB  - Specific gene silencing through RNA interference (RNAi) holds great promise as
      the next-generation therapeutic development platform. Previously, we have shown
      that branched, tripodal interfering RNA (tiRNA) structures could simultaneously
      trigger RNAi-mediated gene silencing of three target genes with 38 nt-long guide
      strands associated with Argonaute 2. Herein, we show that the branched RNA
      structure can trigger effective gene silencing in Dicer knockout cell line,
      demonstrating that the Dicer-mediated processing is not required for tiRNA
      activity. The finding of this study confirms the flexibility of the structure of
      RNAi triggers as well as the length of the guide strand in RNAi-mediated gene
      silencing.

PMID- 29195052
TI  - Accountability for Community-Based Programs for the Seriously Ill.
AB  - Innovation is needed to improve care of the seriously ill, and there are
      important opportunities as we transition from a volume- to value-based payment
      system. Not all seriously ill are dying; some recover, while others are
      persistently functionally impaired. While we innovate in service delivery and
      payment models for the seriously ill, it is important that we concurrently
      develop accountability that ensures a focus on high-quality care rather than
      narrowly focusing on cost containment. The Gordon and Betty Moore Foundation
      convened a meeting of 45 experts to arrive at guiding principles for measurement,
      create a starter measurement set, specify a proposed definition of the
      denominator and its refinement, and identify research priorities for future
      implementation of the accountability system. A series of articles written by
      experts provided the basis for debate and guidance in formulating a path forward
      to develop an accountability system for community-based programs for the
      seriously ill, outlined in this article. As we innovate in existing population
      based payment programs such as Medicare Advantage and develop new alternative
      payment models, it is important and urgent that we develop the foundation for
      accountability along with actionable measures so that the healthcare system
      ensures high-quality person- and family-centered care for persons who are
      seriously ill.

PMID- 29195057
TI  - Novel Radiotherapy Techniques for Breast Cancer.
AB  - During the early decades of radiation therapy for breast cancer, local control of
      disease was documented consistently but, enigmatically, an anticipated impact on
      breast cancer survival was not observed, leading to confusion in our
      understanding of the natural history of breast cancer and radiation effects. Now,
      almost 90 years after its first use in breast cancer, technology developments in
      diagnostic imaging and radiation therapy have elucidated parts of this enigma.
      The data now available demonstrate a significant impact of radiation therapy on
      survival as well as disease control and treatment-related mortality, opening a
      doorway to understanding the powerful impact of radiation therapy on both breast
      cancer and critical organs. Efforts are focused on leveraging novel techniques to
      maximize the benefits of radiation for breast cancer patients.

PMID- 29195058
TI  - Essential Role of IFT140 in Promoting Dentinogenesis.
AB  - Primary cilia, with highly regulated cellular sensory functions, play key roles
      in tissue development and function maintenance. Intraflagellar transport 140
      (IFT140) is a subunit of IFT complex A, which is specialized for retrograde
      transportation in cilia. Mutations of Ift140 are usually associated with
      syndromic ciliopathy and may cause isolated diseases such as retinal dystrophy,
      short ribs, and polycystic kidney. However, the role of IFT140 in tooth
      development has not been well investigated. In this study, a close relationship
      between IFT140 and dentin formation is disclosed. During tooth development,
      IFT140 was highly expressed in odontoblasts. To further understand the role of
      IFT140 in dentinogenesis, Ift140flox/flox/Osx-Cre mouse was generated. The dentin
      thickness of Ift140flox/flox/Osx-Cre mouse is thinner and the dentin formation is
      slower than that in control. In vitro, deletion of IFT140 in odontoblasts led to
      poor odontogenic differentiation, abnormal primary cilia, and decreased Sonic
      hedgehog signaling molecules. More important, due to loss of primary cilia in
      odontoblasts by IFT140 deletion, reparative dentin formation was impaired in a
      tooth-drilling model. These results suggest that cilia gene IFT140 is essential
      in promoting dentin formation and reparation.

PMID- 29195053
TI  - PBP2a in beta-Lactam-Resistant Laboratory Mutants and Clinical Isolates:
      Disruption Versus Reduced Penicillin Affinity.
AB  - Alterations in PBP2a have been recognized in cefotaxime-resistant laboratory
      mutants and beta-lactam-resistant clinical isolates of Streptococcus pneumoniae.
      DNA sequencing revealed fundamental differences between these two settings.
      Internal stop codons in pbp2a occurred in all three laboratory mutants analyzed,
      caused by a mutation in pbp2a of mutant C604, and tandem duplications within
      pbp2a resulting in premature stop codons in another two mutants C403 and C406. In
      contrast, mosaic PBP2a genes were observed in several penicillin-resistant
      clinical isolates from South Africa, the Czech Republic, Hungary, and in the
      clone Poland23F-16, with sequence blocks diverging from sensitive strains by over
      4%. Most of these pbp2a variants except pbp2a from the South African strain
      contained sequences related to pbp2a of Streptococcus mitis B6, confirming that
      this species serves as reservoir for penicillin-resistance determinants.

PMID- 29195051
TI  - The Glymphatic System in Central Nervous System Health and Disease: Past,
      Present, and Future.
AB  - The central nervous system (CNS) is unique in being the only organ system lacking
      lymphatic vessels to assist in the removal of interstitial metabolic waste
      products. Recent work has led to the discovery of the glymphatic system, a glial
      dependent perivascular network that subserves a pseudolymphatic function in the
      brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain
      via periarterial spaces, passes into the interstitium via perivascular astrocytic
      aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF)
      and its solute. Here, we review the role of the glymphatic pathway in CNS
      physiology, the factors known to regulate glymphatic flow, and the pathologic
      processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated
      in disease initiation and progression. Important areas of future research,
      including manipulation of glymphatic activity aiming to improve waste clearance
      and therapeutic agent delivery, are also discussed.

PMID- 29195059
TI  - Retraction of: Tumor Protein D52-Like 2 Accelerates Gastric Cancer Cell
      Proliferation; 10.1089/cbr.2014.1766.

PMID- 29195061
TI  - Retraction of: Tumor Protein D52-Like 2 Contributes to Proliferation of Breast
      Cancer Cells; 10.1089/cbr.2014.1723.

PMID- 29195060
TI  - Structural Studies and Gene Silencing Activity of siRNAs Containing Cationic
      Phosphoramidate Linkages.
AB  - A series of siRNA duplexes containing cationic non-bridging 3',5'-linked
      phosphoramidate (PN) linkages was designed and synthesized using a combination of
      phosphoramidite and H-phosphonate chemistries. Modified oligonucleotides were
      assayed for their thermal stability, helical structure, and ability to modulate
      the expression of firefly luciferase. We demonstrate that PN modifications of
      siRNAs are, in general, minimally destabilizing with respect to duplex thermal
      stability; destabilization can be mitigated through the incorporation of 2'
      modified RNA-like residues or PN conjugates containing ionizable pendant
      moieties. We also demonstrate that single cationic dimethylethylenediamine PN
      linkages have little effect on siRNA potency, whether located in the passenger or
      guide strand of the duplex. Highly modified siRNA passenger strands were further
      modified with up to four cationic PN linkages, with little effect on duplex
      potency or helical structure. We envision that PN modifications could be useful
      in the production of therapeutic siRNAs with optimal biological properties.

PMID- 29195048
TI  - Bendamustine-PAMAM Conjugates for Improved Apoptosis, Efficacy, and in Vivo
      Pharmacokinetics: A Sustainable Delivery Tactic.
AB  - Successful delivery of a chemotherapeutic agent like bendamustine still remains a
      challenge in clinical conditions like chronic lymphatic leukemia (CLL), non
      Hodgkin lymphoma (NHL), and multiple myeloma. We have conjugated bendamustine to
      polyamidoamine (PAMAM) dendrimers after conjugating with N
      (hydroxyethyl)maleimide (spacer) via an ester bond. The particle size of PAMAM
      bendamustine conjugate was 49.8 +/- 2.5 nm. In vitro drug release resulted in
      sustained release with improved solution stability of drug up to 72 h. In a 24 h
      cytotoxicity study by MTT assay against human monoblastic leukemia cells (THP-1),
      the IC50 value for PAMAM-bendamustine was 32.1 +/- 4.8 MUM compared to 50.42 +/-
      3.4 MUM and 2303 +/- 106.5 MUM for bendamustine and PAMAM dendrimer,
      respectively. Significantly higher cell uptake and apoptosis were observed in THP
      1 cells by PAMAM-bendamustine conjugate which was confirmed by flow cytometry and
      confocal laser scanning microscopy. Preliminary in vivo studies undertaken
      included pharmacokinetics studies, organ distribution studies, and tumor
      inhibition studies. In healthy Wistar rat model (1CBM IV push model), the
      pharmacokinetic studies revealed that bioavailability and t1/2 increased
      significantly, i.e., almost 8.5-fold (193.8 +/- 1.116 vs 22.8 +/- 0.158 MUg mL
      1/h) and 5.1-fold (0.75 +/- 0.005 vs 3.85 +/- 0.015 h), respectively, for PAMAM
      bendamustine conjugate compared to pure bendamustine ( p < 0.05), however,
      clearance and volume of distribution were found to be decreased compared to those
      of free drug. The study suggests that PAMAM-bendamustine conjugate was not only
      stable for the longer period but also least toxic and highly taken up by THP-1
      cells to exert an anticancer effect at the reduced dose. Tumor inhibition and
      biodistribution studies in tumor-bearing BALB/c mice revealed that PAMAM
      bendamustine conjugate was more effective than the pure drug and showed higher
      accumulation in the tumor.

PMID- 29195063
TI  - Metabolic and Endocrine Role of Adipose Tissue During Lactation.
AB  - The adipose tissue serves an essential role for survival and reproduction in
      mammals, especially females. It serves primarily as an energy storage organ and
      is directly linked to the reproductive success of mammals. In wild animals,
      adipose tissue function is linked to seasonality of the food supply to support
      fetal growth and milk production. Adipose tissue depots in ruminants and non
      ruminants can secrete many signal molecules (adipokines) that act as hormones and
      as pro- and anti-inflammatory cytokines. The visceral adipose tissue especially
      appears to be more endocrinologically active than other adipose depots. The
      endocrine function is important for the overall long-term regulation of energy
      metabolism and plays an important role in the adaptation to lactation in many
      mammalian species, including humans. Furthermore, endocrine signals from adipose
      tissue depots contribute to fertility modulation, immune function, and
      inflammatory response. Energy homeostasis is modulated by changes in feed intake,
      insulin sensitivity, and energy expenditure, processes that can be influenced by
      adipokines in the brain and in peripheral tissues.

PMID- 29195064
TI  - The Ferrous Awakens.
AB  - Recent discoveries provide a new hope that relapses of several types of cancer
      can be prevented by inducing ferroptosis.

PMID- 29195062
TI  - Compressive Stockings After Hindfoot and Ankle Surgery.
AB  - BACKGROUND: Swelling and pain are common after foot and ankle procedures. We
      hypothesized that compressive stockings (CS) treatment after hindfoot surgery
      would positively influence patient outcomes. METHODS: We undertook this
      randomized controlled trial in 87 consecutive patients to analyze the clinical
      effect of CS after hindfoot and ankle surgery and evaluate CS-wearing compliance
      using sensors that were implanted into CS. Ankle swelling, pain status, quality
      of life (SF-36 score), and the American Orthopaedic Foot & Ankle Score (AOFAS)
      were set as the primary end points. The CS wearing time in hours and percentage
      were investigated as the secondary end points. All participants with CS (group I)
      were informed about the implanted sensor after the CS were taken off. A subgroup
      analysis of group I was performed to detect differences between patients with
      high vs low compliance. RESULTS: At 12 weeks, the results of ankle swelling (mean
      234 mm in group I and 232 mm in group II), pain in the visual analog scale (1.7
      group I vs 1.9 in group II), the SF-36 score (38 points in group I vs 30 points
      in group II), and the AOFAS score (a mean of 76 points in both groups) showed no
      statistical differences between the 2 groups. The mean wearing time was 136
      (range, 0-470) hours, which corresponds to a compliance rate of 65%. Sixteen
      participants had high compliance (>80%, >170 hours), and 21 patients had low or
      noncompliance. The clinical results of patients with high wearing compliance were
      not significantly better compared to the results of patients with low compliance.
      CONCLUSION: CS therapy after ankle and hindfoot surgery was associated with a low
      wearing compliance and did not influence ankle swelling, function, pain, and the
      quality of life compared to the control group. Furthermore, the clinical results
      of patients with high compliance were not better compared to the results of
      patients with low or noncompliance wearing behavior. LEVEL OF EVIDENCE: Level II,
      prospective randomized study of lower quality.

PMID- 29195066
TI  - Physiology Flies with Time.
AB  - The 2017 Nobel Prize in Medicine or Physiology has been awarded to Jeffrey Hall,
      Michael Rosbash, and Michael Young for elucidating molecular mechanisms of the
      circadian clock. From studies beginning in fruit flies, we now know that
      circadian regulation pervades most biological processes and has strong ties to
      human health and disease.

PMID- 29195065
TI  - How Cryo-EM Became so Hot.
AB  - The Royal Swedish Academy of Sciences awarded the 2017 Nobel Prize for Chemistry
      to Jacques Dubochet, Joachim Frank, and Richard Henderson for "developing
      cryoelectron microscopy for the high-resolution structure determination of
      biomolecules in solution." Achieving this goal, which required innovation,
      persistence, and uncommon physical insight, has broadened horizons for structural
      studies in molecular and cell biology.

PMID- 29195067
TI  - As Time Flew By.

PMID- 29195068
TI  - Life Is an N of 1.

PMID- 29195069
TI  - A Nobel Pursuit May Not Run like Clockwork.
AB  - Living in rural Maine, Jeffrey Hall's own rhythm has been thrown upside down
      after he received a very unexpected call one morning on the award of this year's
      Nobel Prize in Physiology or Medicine. Together with Michael Rosbash and Mike
      Young, they were recognized "for their discoveries of molecular mechanisms
      controlling the circadian rhythm." Cell editor Marta Koch caught up with Jeff on
      a calm Sunday morning, when electricity at his house had just returned after
      recent storms. Annotated excerpts from their chat about behavior, misbehavior,
      and the challenges and joys of working with fruit flies, are presented below.

PMID- 29195070
TI  - Tumor Evolution: A Problem of Histocompatibility.
AB  - In this issue of Cell, two articles show that tumor-specific changes in HLA
      mediated antigen presentation affect tumor immunogenicity and may play a role in
      shaping cancer cell survival.

PMID- 29195071
TI  - Phytochromes: Where to Start?
AB  - Phytochrome signaling allows plants to sense and respond to light through gene
      regulation. Ushijima et al. (2017) demonstrate a role for phytochromes in
      widespread regulation of alternative promoter usage, resulting in light-dependent
      protein isoforms with altered subcellular localization that help the plant
      respond metabolically to fluctuating light conditions.

PMID- 29195072
TI  - Platelets, On Your Marks, Get Set, Migrate!
AB  - The idea that anucleate platelets display autonomous migration has long been
      viewed with skepticism. Gaertner et al. provide in vivo evidence that platelets
      undergo active migration at sites of thrombus formation and in inflamed liver
      sinusoids. Integrin-dependent migration allows platelets to scavenge and bundle
      fibrin-bound material, including intravascular bacteria.

PMID- 29195073
TI  - Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating
      Lung Cancer.
AB  - Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis])
      with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer
      immune therapy. Herein, pharmacologic and isoform specificity of HDACis are
      investigated to guide their addition to a DNMTi, thus devising a new, low-dose,
      sequential regimen that imparts a robust anti-tumor effect for non-small-cell
      lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an
      interferon alpha/beta-based transcriptional program with accompanying
      upregulation of antigen presentation machinery, mediated in part through double
      stranded RNA (dsRNA) induction. This is accompanied by suppression of MYC
      signaling and an increase in the T cell chemoattractant CCL5. Use of this
      combination treatment schema in mouse models of NSCLC reverses tumor immune
      evasion and modulates T cell exhaustion state towards memory and effector T cell
      phenotypes. Key correlative science metrics emerge for an upcoming clinical
      trial, testing enhancement of immune checkpoint therapy for NSCLC.

PMID- 29195074
TI  - Myc Cooperates with Ras by Programming Inflammation and Immune Suppression.
AB  - The two oncogenes KRas and Myc cooperate to drive tumorigenesis, but the
      mechanism underlying this remains unclear. In a mouse lung model of KRasG12D
      driven adenomas, we find that co-activation of Myc drives the immediate
      transition to highly proliferative and invasive adenocarcinomas marked by highly
      inflammatory, angiogenic, and immune-suppressed stroma. We identify epithelial
      derived signaling molecules CCL9 and IL-23 as the principal instructing signals
      for stromal reprogramming. CCL9 mediates recruitment of macrophages,
      angiogenesis, and PD-L1-dependent expulsion of T and B cells. IL-23 orchestrates
      exclusion of adaptive T and B cells and innate immune NK cells. Co-blockade of
      both CCL9 and IL-23 abrogates Myc-induced tumor progression. Subsequent
      deactivation of Myc in established adenocarcinomas triggers immediate reversal of
      all stromal changes and tumor regression, which are independent of CD4+CD8+ T
      cells but substantially dependent on returning NK cells. We show that Myc
      extensively programs an immune suppressive stroma that is obligatory for tumor
      progression.

PMID- 29195075
TI  - An Unexpectedly Complex Architecture for Skin Pigmentation in Africans.
AB  - Approximately 15 genes have been directly associated with skin pigmentation
      variation in humans, leading to its characterization as a relatively simple
      trait. However, by assembling a global survey of quantitative skin pigmentation
      phenotypes, we demonstrate that pigmentation is more complex than previously
      assumed, with genetic architecture varying by latitude. We investigate
      polygenicity in the KhoeSan populations indigenous to southern Africa who have
      considerably lighter skin than equatorial Africans. We demonstrate that skin
      pigmentation is highly heritable, but known pigmentation loci explain only a
      small fraction of the variance. Rather, baseline skin pigmentation is a complex,
      polygenic trait in the KhoeSan. Despite this, we identify canonical and non
      canonical skin pigmentation loci, including near SLC24A5, TYRP1, SMARCA2/VLDLR,
      and SNX13, using a genome-wide association approach complemented by targeted
      resequencing. By considering diverse, under-studied African populations, we show
      how the architecture of skin pigmentation can vary across humans subject to
      different local evolutionary pressures.

PMID- 29195076
TI  - Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria.
AB  - Blood platelets are critical for hemostasis and thrombosis and play diverse roles
      during immune responses. Despite these versatile tasks in mammalian biology,
      their skills on a cellular level are deemed limited, mainly consisting in
      rolling, adhesion, and aggregate formation. Here, we identify an unappreciated
      asset of platelets and show that adherent platelets use adhesion receptors to
      mechanically probe the adhesive substrate in their local microenvironment. When
      actomyosin-dependent traction forces overcome substrate resistance, platelets
      migrate and pile up the adhesive substrate together with any bound particulate
      material. They use this ability to act as cellular scavengers, scanning the
      vascular surface for potential invaders and collecting deposited bacteria.
      Microbe collection by migrating platelets boosts the activity of professional
      phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns
      platelets a central role in innate immune responses and identifies them as
      potential targets to dampen inflammatory tissue damage in clinical scenarios of
      severe systemic infection.

PMID- 29195077
TI  - Epsin-Dependent Ligand Endocytosis Activates Notch by Force.
AB  - DSL ligands activate Notch by inducing proteolytic cleavage of the receptor
      ectodomain, an event that requires ligand to be endocytosed in signal-sending
      cells by the adaptor protein Epsin. Two classes of explanation for this unusual
      requirement are (1) recycling models, in which the ligand must be endocytosed to
      be modified or repositioned before it binds Notch and (2) pulling models, in
      which the ligand must be endocytosed after it binds Notch to exert force that
      exposes an otherwise buried site for cleavage. We demonstrate in vivo that
      ligands that cannot enter the Epsin pathway nevertheless bind Notch but fail to
      activate the receptor because they cannot exert sufficient force. This argues
      against recycling models and in favor of pulling models. Our results also suggest
      that once ligand binds receptor, activation depends on a competition between
      Epsin-mediated ligand endocytosis, which induces cleavage, and transendocytosis
      of the ligand by the receptor, which aborts the incipient signal.

PMID- 29195079
TI  - SnapShot: Circadian Clock.
AB  - Most creatures on this planet possess an ability to anticipate upcoming events in
      the environment, courtesy of their circadian clocks. This allows them to prepare
      for those changes instead of being caught by surprise, which could mean the
      difference between life and death. In this SnapShot, we describe the basics of
      how the clock ticks.

PMID- 29195080
TI  - In-Continuity Neck Dissection: Long-Term Oncological Outcomes in Squamous Cell
      Carcinoma of the Buccal Mucosa.
AB  - PURPOSE: To introduce in-continuity neck dissection (ND) in squamous cell
      carcinoma of the buccal mucosa (BMSCC) and to determine its impact on the
      oncologic outcomes of these patients. MATERIALS AND METHODS: A retrospective
      review of patients treated for BMSCC from 2006 through 2016 was performed. Kaplan
      Meier analysis and log-rank test were used to evaluate local control, regional
      control (RC), distant metastasis (DM), and disease-specific survival (DSS) of in
      continuity ND versus discontinuous ND in 220 previously untreated patients with
      BMSCC, followed by a multivariate Cox regression that included all relevant
      variables. RESULTS: Fifty-three patients received discontinuous ND and 167
      patients received in-continuity ND. The 2 groups were comparable. Univariate
      Kaplan-Meier analysis showed that 5-year DSS rates for the discontinuous ND and
      in-continuity ND groups were 38 and 62% (P = .023), respectively. The 5-year RC
      rate for the in-continuity ND group (81%) was significantly better (P = .004)
      than for the discontinuous ND group (54%). At Cox regression analysis, in
      continuity ND meaningfully contributed to a higher RC rate and subsequently
      better DSS. CONCLUSION: Compared with discontinuous ND, in-continuity ND
      predicted favorable oncologic outcomes in patients with BMSCC. In-continuity ND
      could be a practical approach in the surgical management of BMSCC.

PMID- 29195078
TI  - A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000
      Profiles.
AB  - We previously piloted the concept of a Connectivity Map (CMap), whereby genes,
      drugs, and disease states are connected by virtue of common gene-expression
      signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part
      of the NIH LINCS Consortium, made possible by a new, low-cost, high-throughput
      reduced representation expression profiling method that we term L1000. We show
      that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for
      computational inference of the expression levels of 81% of non-measured
      transcripts. We further show that the expanded CMap can be used to discover
      mechanism of action of small molecules, functionally annotate genetic variants of
      disease genes, and inform clinical trials. The 1.3 million L1000 profiles
      described here, as well as tools for their analysis, are available at
      https://clue.io.

PMID- 29195081
TI  - Corrigendum to "Klinefelter's syndrome (47,XXY) is in excess among men with
      Sjogren's syndrome" [Clin. Immunol. 168 (2016) 25-29].

PMID- 29195083
TI  - Evaluation of respiratory dynamics by volumetric capnography during submaximal
      exercise protocol of six minutes on treadmill in cystic fibrosis patients.
AB  - OBJECTIVES: Volumetric capnography provides the standard CO2 elimination by the
      volume expired per respiratory cycle and is a measure to assess pulmonary
      involvement. Thus, the objective of this study was to evaluate the respiratory
      dynamics of healthy control subjects and those with cystic fibrosis in a
      submaximal exercise protocol for six minutes on the treadmill, using volumetric
      capnography parameters (slope 3 [Slp3], Slp3/tidal volume [Slp3/TV], and slope 2
      [Slp2]). METHODS: This was a cross-sectional study with 128 subjects (cystic
      fibrosis, 64 subjects; controls, 64 subjects]. Participants underwent volumetric
      capnography before, during, and after six minutes on the treadmill. Statistical
      analysis was performed using the Friedman, Mann-Whitney, and Kruskal-Wallis
      tests, considering age and sex. An alpha=0.05 was considered. RESULTS: Six
      minutes on the treadmill evaluation: in cystic fibrosis, volumetric capnography
      parameters were different before, during, and after six minutes on the treadmill;
      the same was observed for the controls, except for Slp2. Regarding age, an Slp3
      difference was observed in cystic fibrosis patients regardless of age, at all
      moments, and in controls for age>=12 years; a difference in Slp3/TV was observed
      in cystic fibrosis and controls, regardless of age; and an Slp2 difference in the
      cystic fibrosis, regardless of age. Regarding sex, Slp3 and Slp3/TV differences
      were observed in cystic fibrosis regardless of sex, and in controls in male
      participants; an Slp2 difference was observed in the cystic fibrosis and female
      participants. The analysis between groups (cystic fibrosis and controls)
      indicated that Slp3 and Slp3/TV has identified the CF, regardless of age and sex,
      while the Slp2 showed the CF considering age. CONCLUSIONS: Cystic fibrosis showed
      greater values of the parameters before, during, and after exercise, even when
      stratified by age and sex, which may indicate ventilation inhomogeneity in the
      peripheral pathways in the cystic fibrosis.

PMID- 29195084
TI  - Who needs what and when, and how do we sort that out?

PMID- 29195082
TI  - A cell culture platform for Cryptosporidium that enables long-term cultivation
      and new tools for the systematic investigation of its biology.
AB  - Cryptosporidium parasites are a major cause of diarrhoea that pose a particular
      threat to children in developing areas and immunocompromised individuals.
      Curative therapies and vaccines are lacking, mainly due to lack of a long-term
      culturing system of this parasite. Here, we show that COLO-680N cells infected
      with two different Cryptosporidium parvum strains produce sufficient infectious
      oocysts to infect subsequent cultures, showing a substantial fold increase in
      production, depending on the experiment, over the most optimistic HCT-8 models.
      Oocyst identity was confirmed using a variety of microscopic- and molecular-based
      methods. This culturing system will accelerate research on Cryptosporidium and
      the development of anti-Cryptosporidium drugs.

PMID- 29195085
TI  - Clinical and hematological profile in a newborn cohort with hemoglobin SC.
AB  - OBJECTIVES: Hemoglobin SC is the second most common variant of sickle-cell
      disease worldwide, after hemoglobin SS. The objectives of the study were to
      describe the clinical and laboratory characteristics of hemoglobin SC disease in
      children from a newborn screening program and treated at a blood center.
      METHODOLOGY: This study assessed a cohort of 461 infants born between 01/01/1999
      and 12/31/2012 and followed-up until 12/31/2014. Clinical events were expressed
      as rates for 100 patient-years, with 95% confidence intervals. Kaplan-Meier
      survival curves were created. RESULTS: The median age of patients was 9.2 years;
      47.5% were female. Mean values of blood tests were: hemoglobin, 10.5g/dL;
      reticulocytes, 3.4%; white blood cells, 11.24*109/L; platelets, 337.1*109/L; and
      fetal hemoglobin, 6.3%. Clinical events: acute splenic sequestration in 14.8%,
      blood transfusion 23.4%, overt stroke in 0.2%. The incidence of painful vaso
      occlusive episodes was 51 (48.9-53.4) per 100 patient-years and that of
      infections, 62.2 episodes (59.8-64.8) per 100 patient-years. Transcranial Doppler
      ultrasonography (n=71) was normal given the current reference values for SS
      patients. Hydroxyurea was given to ten children, all of whom improvement of
      painful crises. Retinopathy was observed in 20.3% of 59 children who underwent
      ophthalmoscopy. Avascular necrosis was detected in seven of 12 patients
      evaluated, predominantly in the left femur. Echocardiogram compatible with
      pulmonary hypertension was recorded in 4.6% of 130 children, with an estimated
      average systolic pulmonary artery pressure of 33.5mmHg. The mortality rate from
      all causes was 4.3%. CONCLUSIONS: Clinical severity is variable in SC
      hemoglobinopathy. Several children have severe manifestations similar to those
      with SS disease.

PMID- 29195087
TI  - From ancestral peptides to designed proteins.
AB  - The diversity of modern proteins arose through the combinatorial shuffling and
      differentiation of a limited number of autonomously folding domain prototypes,
      but the origin of these prototypes themselves has long remained poorly
      understood. In recent years, the proposal that they originated by repetition,
      accretion, and recombination from an ancestral set of peptides, which evolved as
      cofactors of RNA-based replication and catalysis, has gained wide acceptance,
      supported by the systematic identification of such ancestral peptides and the
      experimental recapitulation of the mechanisms by which they could have yielded
      the first folded proteins. Inspired by this evolutionary process, protein
      engineers have seized on design from pre-optimized peptide components as a
      powerful approach to generating proteins with novel topology and functionality.

PMID- 29195086
TI  - Postmortem MRI and histology demonstrate differential iron accumulation and
      cortical myelin organization in early- and late-onset Alzheimer's disease.
AB  - Previous MRI studies reported cortical iron accumulation in early-onset (EOAD)
      compared to late-onset (LOAD) Alzheimer disease patients. However, the pattern
      and origin of iron accumulation is poorly understood. This study investigated the
      histopathological correlates of MRI contrast in both EOAD and LOAD. T2*-weighted
      MRI was performed on postmortem frontal cortex of controls, EOAD, and LOAD.
      Images were ordinally scored using predefined criteria followed by histology.
      Nonlinear histology-MRI registration was used to calculate pixel-wise spatial
      correlations based on the signal intensity. EOAD and LOAD were distinguishable
      based on 7T MRI from controls and from each other. Histology-MRI correlation
      analysis of the pixel intensities showed that the MRI contrast is best explained
      by increased iron accumulation and changes in cortical myelin, whereas amyloid
      and tau showed less spatial correspondence with T2*-weighted MRI.
      Neuropathologically, subtypes of Alzheimer's disease showed different patterns of
      iron accumulation and cortical myelin changes independent of amyloid and tau that
      may be detected by high-field susceptibility-based MRI.

PMID- 29195088
TI  - Early inhibitory control and working memory abilities of children prenatally
      exposed to methadone.
AB  - BACKGROUND: Methadone maintenance is the most common method of treating opioid
      dependent pregnant women. However, little is known about the impact of prenatal
      methadone exposure on child neurocognitive development. AIMS: To examine the
      early executive functioning of children born to methadone-maintained mothers, and
      to assess relations between executive functioning and later emotional and
      behavioral adjustment. STUDY DESIGN: Prospective longitudinal study.
      PARTICIPANTS: The sample consisted of 68 methadone-exposed children and 88 non
      methadone-exposed children. OUTCOME MEASURES: At age 2years, children's
      inhibitory control and working memory were assessed using the Snack Delay and
      Three Boxes tasks. At 2 and 4.5years, their emotional and behavioral adjustment
      was assessed using the caregiver-completed Strengths and Difficulties
      Questionnaire. RESULTS: Methadone-exposed children had poorer inhibitory control
      than non-exposed children (p<0.0001). These differences were explained by
      maternal education and prenatal benzodiazepine use. With respect to working
      memory, although both groups performed similarly on the first trial set, non
      exposed children significantly improved their performance on the second trial set
      (p=0.002), while methadone-exposed children did not (p=0.92). Inhibitory control
      at age 2years was predictive of higher conduct (p=0.001), hyperactivity
      (p=0.0001), peer relationship (p=0.02), and total (p<0.0001) problems at 4.5years
      even after adjustment for behavioral problems at 2years. CONCLUSIONS: Methadone
      exposed children demonstrate difficulties with inhibitory control and possibly
      sustained attention/learning. These difficulties were explained by factors
      correlated with maternal prenatal methadone use. Longer-term follow-up of these
      children is needed to understand the effects of prenatal methadone exposure and
      related maternal factors on executive functioning and behavioral adjustment.

PMID- 29195089
TI  - Immunotoxicity of bisphenol S and F are similar to that of bisphenol A during
      zebrafish early development.
AB  - Bisphenol S (BPS) and bisphenol F (BPF) have been increasingly used as
      alternatives to bisphenol A (BPA) owing to health concerns. The present study
      aims to evaluate the impact of these two BPA analogs on oxidative stress and the
      immune system during zebrafish embryonic and larval development. Environmentally
      relevant levels of BPS and BPF exposure could increase reactive oxygen species
      (ROS) content, nitric oxide (NO) content, nitric oxide synthase (NOS) activity,
      and the expression of immunity-related genes in concentration dependent manners
      during the early developmental stages in zebrafish. At a concentration of 100
      MUg/L, BPS and BPF showed similar effects on the immune toxicity of zebrafish as
      that of BPA. Moreover, BPS and BPF induced both eralpha and nf-kappab expression,
      and antagonists of estrogen receptor and NF-kappaB blocked the effects on
      immunity-related gene expression, providing evidence that the two pathways
      mediate the actions of BPS and BPF on fish immune response and functions. Thus we
      conclude that the presence of BPS and BPF in the environment, similar to BPA, may
      also pose risks to ecosystem and human health and cannot be widely used without
      limitations and precautions.

PMID- 29195091
TI  - Iodinated X-ray contrast media in aquatic environment in general and in drinking
      water in particular: A possible source for the primary sensitization of patients.

PMID- 29195090
TI  - Effects of imidazolium-based ionic liquids with different anions on wheat
      seedlings.
AB  - The effects of five imidazolium ionic liquids with different anions were studied
      in hydroponically grown wheat seedlings at concentrations of 50, 100, 150, 200,
      250, and 300 mg L-1. The results showed that shoots and roots grew shorter and
      dry weight decreased with increasing concentrations of ionic liquids. Moreover,
      the antioxidant enzyme activities decreased and malondialdehyde (MDA) content was
      greater in the leaves of wheat seedlings subjected to ionic liquid (IL)
      treatments. The order of influence of ionic liquids on these indexes was
      [C4mim][TfO]> [C4mim][Cl]> [C4mim][BF4]> [C4mim][Lact]> [C4mim][Ala]. A
      transmission electron microscope (TEM) was used to observe leaf and root cellular
      structures, such as chloroplast, nucleus, mitochondria, and rough endoplasmic
      reticulum, in wheat exposed to ionic liquids at a concentration of 150 mg L-1.
      The results showed that the cellular structures of wheat were affected, and the
      degree of the effect of five ILs was consistent with the general trend of the
      measured indexes in this study. Ionic liquids influence the growth of plants by
      impeding growth, disrupting metabolic physiology and changing cellular
      structures. The degree of toxicity of imidazolium-based ionic liquids with
      different anions varies.

PMID- 29195092
TI  - Dechlorinating performance of Dehalococcoides spp. mixed culture enhanced by
      tourmaline.
AB  - Dehalococcoides spp. were extensively studied and applied to in-situ
      trichloroethylene (TCE) remediation since it is the only genus that can reduce
      TCE to harmless ethene completely. However, this technology was hindered because
      of the requirement of electron donor (i.e. hydrogen or fermentable organic
      substrate). Considering the spontaneous electric field and in-situ hydrogen
      production capacity of tourmaline, this mineral was used as an environmental
      friendly bio-promoter for dechlorinating mixed culture containing Dehalococcoides
      spp. in this work. Research results showed that biodegradation of TCE and the
      intermediates were both significantly improved by tourmaline. The first-order TCE
      degradation rate coefficient increased from 0.0125 h-1 for the tourmaline-free
      system to 0.0306 h-1 for the system combined with 5 g L-1 tourmaline, and ethene
      production increased by 36%. The outstanding TCE-degrading ability in the
      tourmaline-bacteria system without the addition of fermentative electron donor
      (i.e. methanol) indicated that tourmaline could also produce electron donor to
      support dechlorinating bacteria. Tourmaline could have direct electric
      biostimulatory effect and indirect enhanced effect associated with water-derived
      H2 production in the electric field of tourmaline. Meanwhile, PCR-DGGE analysis
      exhibited that tourmaline could accelerate the succession of a bacterial,
      dechlorinating community. The distinctive effects of tourmaline on bacteria were
      related to its stable electric properties. Therefore, tourmaline could be
      continuously used in the bioremediation. The present study provided a safe,
      convenient and persistent alternative to the commonly used enhancement approaches
      for anaerobic reductive dechlorination process.

PMID- 29195093
TI  - Synthesis of derivatives of cleistopholine and their anti-acetylcholinesterase
      and anti-beta-amyloid aggregation activity.
AB  - A series of 6- and 9-substituted cleistopholine derivatives has been designed,
      synthesized and investigated to inhibit the aggregation of acetylcholinesterase
      (AChE), butyrylcholinesterase (BChE) and beta-myloid (A beta). Results showed
      that these synthetic compounds had excellent AChE inhibitory activity and a
      significant in vitro inhibitory potency toward the self-induced A beta
      aggregation. When SH-SY5Y cells were treated with these substituted
      cleistopholine derivatives during they overexpressed the Swedish mutant form of
      human beta -amyloid precursor protein (APPsw), A beta 42 secretion levels were
      significantly reduced. According to a parallel artificial membrane permeation
      assay for BBB, seven out of these sixteen synthetic compounds probably could
      cross the blood-brain barrier (BBB) to reach their targets in the central nervous
      system (CNS).

PMID- 29195095
TI  - Uniquely high turnover of nickel in contaminated oysters Crassostrea
      hongkongensis: Biokinetics and subcellular distribution.
AB  - Despite the environmental concerns regarding nickel (Ni) especially in China, it
      has received little attention in aquatic animals due to its comparatively weak
      toxicity. In the present study, we explored the bioaccumulation, biokinetics, and
      subcellular distribution of Ni in an estuarine oyster Crassostrea hongkongensis.
      We demonstrated that Ni represented a new pattern of bioaccumulation in oysters
      characterized by rapid elimination and low dissolved uptake. The waterborne
      uptake rate constant and dietary assimilation efficiency were 0.036L/g/h and 28%,
      respectively, and dissolved uptake was the predominant exposure route. The efflux
      rate constant was positively related to tissue Ni concentration, with the highest
      efflux of 0.155d-1. Such high elimination resulted in a high Ni turnover and
      steady-state condition reached rapidly, as shown with a 4-week waterborne
      exposure experiment at different Ni concentrations. Ni in oysters was mainly
      sequestered in metallothionein-like protein (MTLP), metal-rich granule, and
      cellular debris. MTLP was the most important binding fraction during accumulation
      and depuration, and played a dynamic role leading to rapid Ni elimination. Pre
      exposure to Ni significantly reduced the dissolved uptake, probably accompanied
      by depressed filtration activity. Overall, the high turnover and regulation of Ni
      in oysters were achieved by enhanced efflux, suppressed uptake, and sequestration
      of most Ni into the detoxified pool.

PMID- 29195094
TI  - Increases in the competitive fitness of West Nile virus isolates after
      introduction into California.
AB  - To investigate the phenotypic evolution of West Nile virus (WNV) in California,
      we competed sixteen isolates made during 2007-08 against COAV997-5nt, a
      genetically marked clone from the founding 2003 California isolate COAV997-2003.
      Using in vivo fitness competitions in House Finches (HOFI) and Culex tarsalis
      mosquitoes, we found that the majority of WNV WN02 and SW03 genotype isolates
      exhibited elevated replicative fitness in both hosts compared to COAV997-5nt.
      Increased replicative capacity in HOFIs was not associated with increased
      mortality, indicating that these isolates had not gained avian virulence. One
      WN02 isolate from Coachella Valley, a region geographically close to the
      isolation of COAV997, showed neutral fitness in HOFIs and reduced fitness in Cx.
      tarsalis. Two isolates from Kern County and Sacramento/Yolo County out-competed
      COAV997-nt in HOFIs, but were transmitted less efficiently by Cx. tarsalis.
      Competition demonstrated neutral or increased fitness that appeared independent
      of both WN02 and SW03 genotypes.

PMID- 29195096
TI  - Role of neurexin2a in lead-induced locomotor defect in developing zebrafish.
AB  - Low-dose chronic lead (Pb) exposure interferes with the development of the
      nervous system, which may lead to learning disabilities, behavioral
      abnormalities, and mental retardation. Neurexins (Nrxns) are synaptic cell
      adhesion molecules associated with neurological disorders. We hypothesized that
      Pb can affect the expression of nrxns during synapse formation and alter the
      phenotype behavior. Here, apoptosis, nrxns mRNA expression, and alterations of
      locomotion were examined after exposure to Pb in zebrafish embryos/larvae. To
      confirm the function of nrxn2a, rescue experiments were performed using beta
      nrxn2a mRNA microinjection. Pb exposure increased apoptosis and altered locomotor
      behavior in zebrafish larvae. Quantitative PCR showed that among several synaptic
      adhesion molecules, only nrxn2a were affected by Pb exposure. Moreover, exposure
      to Pb at 10MUmol/L upregulated mRNA expression of nrxn1a and nrxn3a at 24h post
      fertilization (hpf) and downregulated expression at 48 hpf, whereas the
      expression remained unchanged at 72 hpf. Only the two isoforms of nrxn2a were
      downregulated by Pb at 10MUmol/L at all three time points. Rescue experiments
      showed that beta-nrxn2a mRNA injection recovered the decreased locomotor activity
      and the increased apoptosis induced by Pb. In addition, overexpression of beta
      nrxn2a mRNA upregulated alpha-nrxn2a. These data indicated that Pb inhibited the
      expression of nrxn2a genes, which play a critical role in neural development, and
      further altered the behavior of zebrafish embryos/larvae.

PMID- 29195097
TI  - Emergency insertion of the LMA protector airway in patients in the lateral
      position.

PMID- 29195098
TI  - Respiratory effect of interscalene brachial plexus block vs combined
      infraclavicular plexus block with suprascapular nerve block for arthroscopic
      shoulder surgery.

PMID- 29195100
TI  - Clinical experiences of unilateral anterior sub-costal quadratus lumborum block
      for a nephrectomy.

PMID- 29195099
TI  - Clinical effects of prophylactic use of phentolamine in patients undergoing
      pheochromocytoma surgery.

PMID- 29195101
TI  - Inhibition of aluminum dust explosion by NaHCO3 with different particle size
      distributions.
AB  - NaHCO3 with three particle size distributions was employed to determine the
      minimum inerting concentration (MIC, g/m3) for the explosion of 5MUm and 30MUm
      aluminum dust in a standard 20L spherical chamber and thus examine the effect of
      particle size on the inhibition efficiency. Results showed that the MIC
      significantly increases as the aluminum particle size decreases from 30MUm to
      5MUm. For 30MUm aluminum, the MIC dramatically decreased with the reduction in
      the NaHCO3 particle size. By contrast, for 5MUm aluminum, the MIC was nearly
      independent of the particle size of NaHCO3 in the range studied. Time-scale
      analysis indicated that the decomposition of NaHCO3 must be faster than the
      aluminum combustion reaction for effective chemical inhibition. Scanning electron
      microscopy showed that the particles of the explosion residues of a NaHCO3/Al
      mixture were considerably larger than those of pure aluminum explosion residues.
      A diameter ratio betamix was defined to evaluate the degree of incomplete
      reaction promoted by NaHCO3. The composition of the explosion products was
      analyzed by X-ray photoelectron spectroscopy, and the data revealed that Na2CO3
      and Al2O3 are the major species of the products. An inhibition mechanism was
      proposed based on these results.

PMID- 29195102
TI  - Impact of alkali cations on properties of metakaolin and metakaolin/slag
      geopolymers: Microstructures in relation to sorption of 134Cs radionuclide.
AB  - Radio-cesium constitutes major environmental threats. Sorption of hazardous
      species onto geopolymeric sorbents is relatively recent and may give information
      about the retention mechanisms when geopolymers are applied to immobilize
      radwastes. Here, Na-MK, K-MK, Na-MKBFS, and K-MKBFS geopolymeric sorbents were
      synthesized from metakaolin (MK) and blast furnace slag (BFS) and were
      characterized using XRD, XRF, FT-IR, DTA/TGA and SEM. FT-IR/XRF results clarified
      the impact of mono-valent alkali cation (M+) in dividing the sorbents into Al
      rich (sodium-based) and Si-rich (potassium-based). All sorbents were amorphous to
      semi-crystalline containing mica-phyllosilicates (greater in Si-rich),
      tobermorites (greater in MKBFS-based), gehlenite, calcite, quartz, hematite and
      hydrotalcite. Isotherms of 134Cs radionuclide sorption were constructed, being
      regular with a positive temperature effect. Al-rich sorbents gave higher sorption
      capacities than Si-rich ones. Na-MK sorbent recorded the more distinctive
      sorption capacity (74.95mg/g; at 333K). Langmuir, Freundlich and D-R models were
      used to disclose the capacities and mechanisms governing the sorption processes.
      Sorption of Cs+ onto the examined sorbents was favorable. All systems were
      controlled by ion exchange mechanism, except 134Cs/K-MK system which was
      controlled by physi- sorption mechanism. 134Cs/Na-MK GP system was the only
      spontaneous among all. The endothermic natures were the common denominator
      between the tested systems.

PMID- 29195103
TI  - Chromium-zinc ferrite nanocomposites for the catalytic abatement of toxic
      environmental pollutants under ambient conditions.
AB  - Catalytic abatement of 4-chlorophenol, 2,4-dichlorophenol and 2,4-dichlorophenoxy
      acetic acid in water was investigated by peroxide oxidation over chromium
      substituted zinc ferrite nanocomposites at ambient conditions. The structural and
      chemical properties of composites synthesized by sol-gel auto combustion method
      was studied by X-ray diffraction, Fourier Transform Infra-Red spectroscopy,
      Transmission Electron Microscopy, surface area, X-ray Fluorescence spectroscopy,
      Temperature Programmed Reduction and Desorption techniques. Complete removal of 4
      CP, DCP and 2,4-D was achieved within 60, 75 and 90min with 96.7/90.5%,
      93.88/77.23% and 88.55/62.1% of COD/TOC removal respectively at 298K and 343K.
      Influence of reaction variables including reaction temperature, oxidant
      concentration, substrate concentration, catalyst dosage and its composition on
      the removal efficiency was studied. Kinetic study revealed that wet peroxide
      oxidation followed a first order kinetic model with rate constant and activation
      energy of 3.5*10-2min-1/10.7kJ/mole, 9.5*10-3min-1/12.9kJ/mole and 2.29*10-2min
      1/17.7kJ/mole respectively for 4-CP, DCP and 2,4-D. The results of five
      consecutive catalytic runs from X-ray diffraction, Brunauer Emmet Teller surface
      area and leaching studies from Atomic Absorption Spectrophotometry (AAS) revealed
      the excellent stability of the catalyst. Scavenging effect of n-butanol on
      hydroxyl radical indicated a heterogeneous free radical mechanism.

PMID- 29195104
TI  - Initial psychometrics, outcomes, and correlates of the Repetitive Body Focused
      Behavior Scale: Examination in a sample of youth with anxiety and/or obsessive
      compulsive disorder.
AB  - BACKGROUND: Body-Focused Repetitive Behaviors (BFRBs), including skin-picking,
      hair-pulling, and nail-biting, commonly occur in youth, even at
      elevated/problematic levels, and are associated with a number of other
      psychiatric symptoms. The present study examined the internal consistency of a
      brief screening tool for BFRBs as well as the prevalence, severity, and
      correlates of BFRBs in a sample of youth with a primary anxiety or obsessive
      compulsive disorder (OCD). METHODS: Ninety-three youth-parent dyads presenting
      for treatment for anxiety or OCD completed study measures including the
      Repetitive Body Focused Behavior Scale - Parent (RBFBS), which includes subscales
      for skin-picking, hair-pulling, and nail-biting, as well as a number of
      additional clinician-, parent-, and child-rated scales. RESULTS: The RBFBS
      demonstrated good to excellent internal consistency. BFRBs were endorsed in 55%
      of youths, with elevated levels in 27%. Skin-picking was the most common BFRB
      (38%), followed by nail-biting (34%) and hair-pulling (4%). Youth with BFRBs, as
      compared to those without, were rated as more avoidant by their parents. Among
      those with BFRBs, more avoidant tendencies, anxiety sensitivity, and child-rated
      panic, separation, and generalized anxiety symptoms were associated with elevated
      BFRB severity. BFRBs were equally common but more likely to be elevated among
      youth with a primary anxiety, than OCD, diagnosis. DISCUSSION: Results provide
      initial support for the RBFBS as a brief screening tool for the three common
      BFRBs. In addition, the results suggest avoidant tendencies and physical
      manifestations of distress may be particularly relevant to the escalation of BFRB
      symptoms in youth.

PMID- 29195105
TI  - LGI1 antibody encephalitis - Detailed clinical, laboratory and radiological
      description of 13 cases in China.
AB  - BACKGROUND AND PURPOSE: LGI1 antibody encephalitis is a synaptic autoimmune
      disorder that was first reported in 2010. To date, LGI1 antibody encephalitis is
      a widely-recognized disease in neurology and psychiatry. In order to aid clinical
      recognition of the condition, we analyze the clinical characteristics of 13
      Chinese LGI1 antibody encephalitis patients. METHODS: We analyzed clinical
      features of patients admitted to the West China Hospital who had been diagnosed
      with LGI1 antibody encephalitis from 2015 to 2017. RESULTS: The median age of the
      13 patients was 40.5years. There were 8 female patients, and 1 patient younger
      than 20years. The initial symptoms in 6 patients (46%) were psychiatric in
      nature. After treatment, 10 patients (77%) recovered gradually, and 11 patients
      (85%) showed improvement of psychiatric symptoms. CONCLUSIONS: LGI1 antibody
      encephalitis should be suspected in patients who developed a rapid change in
      behavior or psychosis, seizures, or cognition. Timely diagnosis and treatment may
      yield favorable prognosis.

PMID- 29195106
TI  - Mental health of caregivers of individuals with disabilities: Relation to
      Suicidal Ideation.
AB  - OBJECTIVE: The mental health of caregivers of individuals with disabilities is
      frequently neglected. This study investigated mental health status and Suicidal
      Ideation (SI) among caregivers and examined the predictive factors for SI.
      METHOD: Caregivers of individuals with physical or mental disabilities in a
      tertiary hospital in southern Taiwan were recruited through snowball sampling.
      They were assessed by self-report questionnaires, consisting of the Taiwanese
      Depression Questionnaire and a subset of the three-item Chinese Health
      Questionnaire, to assess probable depression and common mental disorders (CMDs),
      with cutoff points of 19 and 3, respectively. RESULTS: Among 255 caregivers,
      32.9% had probable depression, 37.6% had probable CMDs, and 18.8% experienced SI.
      The level of SI was correlated with primary caregivers (p=0.015), lack of support
      from co-caregivers (p=0.023), caring for younger patients (p=0.010), caring for
      patients with mental disability (p=0.019) or catastrophic diseases (p=0.005), and
      caregivers' probable depression (p<0.001) and CMDs (p<0.001). Regression analysis
      predicted the greatest SI among caregivers caring for younger patients (odds
      ratio [OR]=0.98, p=0.048) and for patients with catastrophic diseases (OR=3.15,
      p=0.008), as well as for caregivers with probable depression (OR=3.90, p=0.010)
      or CMDs (OR=9.40, p<0.001). CONCLUSIONS: When examining SI, clinicians should be
      aware of the mental health of caregivers who are responsible for people with
      disability. In particular, they should be vigilant regarding caregivers of
      individuals who are of younger age or have catastrophic diseases and regarding
      caregivers who exhibit probable depression and CMDs.

PMID- 29195107
TI  - A cross-national study to objectively evaluate the quality of diverse simulation
      approaches for undergraduate nursing students.
AB  - The aim of this paper is to report the results of a cross-national study that
      evaluated a range of simulation sessions using an observation schedule developed
      from evidence-based quality indicators. Observational data were collected from 17
      simulation sessions conducted for undergraduate nursing students at three
      universities in Australia and the United Kingdom. The observation schedule
      contained 27 questions that rated simulation quality. Data were collected by
      direct observation and from video recordings of the simulation sessions. Results
      indicated that the highest quality scores were for provision of learning
      objectives prior to the simulation session (90%) and debriefing (72%). Student
      preparatiosn and orientation (67%) and perceived realism and fidelity (67%) were
      scored lower than other components of the simulation sessions. This observational
      study proved to be an effective strategy to identify areas of strength and those
      needing further development to improve simulation sessions.

PMID- 29195108
TI  - Novel combined index of cardiometabolic risk related to periarterial fat improves
      the clinical prediction for coronary artery disease complexity.
AB  - BACKGROUND AND AIMS: Cardiovascular (CV) risk assessment based on conventional
      risk factors has a limited performance in the prediction of obstructive coronary
      artery disease (CAD). Therefore, our aim was to provide a complete assessment on
      the associations between single or combined cardiovascular ultrasound indexes and
      the complexity of CAD in high and very-high risk patients. METHODS: Two hundred
      fifteen patients scheduled for elective coronary angiography were enrolled in the
      study (F/M: 80/135 pts; age: 61.8 +/- 7.9 years). Detailed clinical
      characteristics, including several obesity parameters, and the following
      ultrasound indexes were obtained: carotid intima-media thickness (IMT) and extra
      media thickness (EMT), epicardial fat thickness (EFT) and intra-abdominal fat
      thickness (IAT). CAD severity and complexity were assessed based on the well
      evidenced SYNTAX score (SS) algorithm. RESULTS: The study patients (79% with a
      very high CV risk) had central obesity (77%), and arterial hypertension (81%),
      one-third (37%) had diabetes and most of the individuals (74%) were current or
      previous smokers. In the study group, male sex, higher number of CV risk factors,
      diabetes and increased carotid vascular indexes (IMT or EMT >= 900 MUm) were
      associated with significantly higher SS (p < 0.05). Paradoxically, obese patients
      revealed a significantly lower SS compared to non-obese individuals (3.65 +/-
      6.66 vs. 5.93 +/- 8.8; p < 0.01), which was not explained by the number of CV
      risk factors or age. All the ultrasound indexes (except for visceral fat - IAT)
      revealed significant associations with the SS and the highest correlation
      coefficient was found for PATIMA combined index (r = 0.45; p < 0.01). Hence, none
      of the obesity-related clinical indexes showed any associations with CAD
      complexity. Multivariate regression analysis showed that male sex, chronic kidney
      disease and the PATIMA index were independently associated with the Syntax Score.
      The ROC analysis showed that the highest sensitivity (71% and 82%) and
      specificity (77% and 72%) in prediction of either SS > 1 or SS > 7 were found for
      the combined PATIMA index (negative predictive value = 92% for SS > 7).
      CONCLUSIONS: We present the first study showing that a combination of ultrasound
      indexes related to periarterial fat and vascular wall (PATIMA index) is
      associated with more complex CAD in high and very-high risk patients. PATIMA
      index revealed improved predictive value compared to other single ultrasound
      indexes and clinical risk assessment.

PMID- 29195109
TI  - Association of alcohol consumption and aortic calcification in healthy men aged
      40-49 years for the ERA JUMP Study.
AB  - BACKGROUND AND AIMS: Several studies have reported a significant inverse
      association of light to moderate alcohol consumption with coronary heart disease
      (CHD). However, studies assessing the relationship between alcohol consumption
      and atherosclerosis have reported inconsistent results. The current study was
      conducted to determine the relationship between alcohol consumption and aortic
      calcification. METHODS: We addressed the research question using data from the
      population-based ERA-JUMP Study, comprising of 1006 healthy men aged 40-49 years,
      without clinical cardiovascular diseases, from four race/ethnicities: 301 Whites,
      103 African American, 292 Japanese American, and 310 Japanese in Japan. Aortic
      calcification was assessed by electron-beam computed tomography and quantified
      using the Agatston method. Alcohol consumption was categorized into four groups:
      0 (non-drinkers), <=1 (light drinkers), >1 to <=3 (moderate drinkers) and >3
      drinks per day (heavy drinkers) (1 drink = 12.5 g of ethanol). Tobit conditional
      regression and ordinal logistic regression were used to investigate the
      association of alcohol consumption with aortic calcification after adjusting for
      cardiovascular risk factors and potential confounders. RESULTS: The study
      participants consisted of 25.6% nondrinkers, 35.3% light drinkers, 23.5% moderate
      drinkers, and 15.6% heavy drinkers. Heavy drinkers [Tobit ratio (95% CI) = 2.34
      (1.10, 4.97); odds ratio (95% CI) = 1.67 (1.11, 2.52)] had significantly higher
      expected aortic calcification score compared to nondrinkers, after adjusting for
      socio-demographic and confounding variables. There was no significant interaction
      between alcohol consumption and race/ethnicity on aortic calcification.
      CONCLUSIONS: Our findings suggest that heavy alcohol consumption may be an
      independent risk factor for atherosclerosis.

PMID- 29195111
TI  - The role of awareness in the cognitive control of single-prime negative priming.
AB  - Single-prime negative priming refers to a phenomenon whereby repeating a single
      prime as a probe target slows responses to that target. This phenomenon is
      modulated by cognitive control when the contingency between the prime and probe
      target is higher than chance. The present study investigated the role of prime
      awareness and awareness of the contingency within the control mechanism during
      single-prime negative priming. Results showed that while single-prime negative
      priming occurred regardless of participant awareness, the control mechanism was
      modulated by prime awareness and perceived contingency.

PMID- 29195110
TI  - Brachial artery diameter as a marker for cardiovascular risk assessment: FMD-J
      study.
AB  - BACKGROUND AND AIMS: Baseline brachial artery (BBA) diameter has been reported to
      be a potential confounding factor of flow-mediated vasodilation (FMD). The
      purpose of this study was to evaluate the relationships between BBA diameter and
      cardiovascular risk factors and compare the diagnostic accuracy of BBA diameter
      in subjects without cardiovascular risk factors and patients with cardiovascular
      disease (CVD) with that of FMD. METHODS: We measured BBA diameter and FMD in 5695
      male subjects. In addition, we retrospectively investigated the incidence of
      cardiovascular events using another population sample consisting of 440 male
      subjects, to compare the accuracy of BBA diameter with that of FMD in predicting
      cardiovascular events. RESULTS: BBA diameter and FMD significantly correlated
      with age, body mass index, systolic blood pressure, diastolic blood pressure,
      triglycerides, high-density lipoprotein cholesterol, and glucose as well as
      Framingham risk score. The prevalence of cardiovascular risk factors and CVD
      increased with the increase in BBA diameter and FMD. Area under the curve (AUC)
      value of the receiver operating characteristic (ROC) curve for BBA diameter to
      diagnose subjects without cardiovascular risk factors (0.59 vs. 0.62, p = 0.001)
      or patients with CVD (0.58 vs. 0.64, p < 0.001) was significantly lower than that
      for FMD. In the retrospective study, the AUC value of the ROC curve for BBA
      diameter to predict first major cardiovascular events was significantly lower
      than that of FMD (0.50 vs. 0.62, p = 0.03). CONCLUSIONS: In men, BBA diameter was
      inferior to FMD for assessment of cardiovascular risk.

PMID- 29195112
TI  - Promoting honesty in young children through observational learning.
AB  - The observational learning approach, developed more than a half century ago,
      suggests that it is possible to promote desirable social behaviors through peer
      observation. However, this idea has yet to be put to a rigorous empirical test.
      The current research sought to fill this gap by examining whether honesty can be
      promoted in children by allowing them to observe a peer's display of honest
      behavior. The dependent measure was whether 5-year-old children who had cheated
      by peeking in a guessing game would confess to it. Study 1 showed that simply
      observing a classmate confess to peeking did not promote honesty. However,
      children who observed a classmate confess to peeking and receive praise and a
      small prize from an experimenter did became more honest. Study 2 replicated the
      effect with a weaker manipulation that involved praise for the confessing peer
      but no prize, which suggests that verbal feedback alone was a sufficient benefit.
      These findings point to new strategies for promoting honesty in young children
      and demonstrate that young children's observations of the social consequences of
      others' sociomoral behavior can help them to guide their own behavior.

PMID- 29195113
TI  - A case of multiple sclerosis and necrotizing autoimmune myopathy with anti-SRP
      antibodies.
AB  - Only few reports exist regarding the coexistence of multiple sclerosis (MS) and
      autoimmune myopathies. We describe the case of a man with a long history of
      undiagnosed left lower limb motor impairment who was hospitalized for subacute
      onset of a myopathic syndrome. In addition, neurological examination revealed
      sensory impairment and pyramidal signs in the left limbs. Muscle biopsy revealed
      a necrotizing myopathy and serum anti-signal recognition particle (SRP)
      antibodies were found. Brain and spinal cord MRI displayed several non-enhancing
      demyelinating lesions, and CSF-restricted oligoclonal bands were detected.
      Multimodal evoked potentials showed increased latency of central conduction.
      Total body PET-CT did not reveal malignancies. A final diagnosis of anti-SRP
      necrotizing autoimmune myopathy (NAM) and MS was made, and subsequent therapy
      with azathioprine resulted in a complete stability for both diseases during the
      follow up. To the best of our knowledge this is the first reported case of
      concomitant NAM and MS.

PMID- 29195114
TI  - Cutaneous anaplastic large cell lymphoma in a multiple sclerosis patient
      receiving Fingolimod.
AB  - BACKGROUND: Previous reports of cutaneous neoplastic lesions secondary to
      Fingolimod treatment among multiple sclerosis patients. OBJECTIVE: Reporting a
      case of cutaneous large cell lymphoma in a multiple sclerosis patient during
      Fingolimod treatment. METHOD: Case study. RESULT: Our patient developed CD30+
      cutaneous large cell lymphoma two years after initiation of Fingolimod treatment
      and her symptoms regressed following the cessation of treatment. CONCLUSION: This
      report indicates that cutaneous lymphoid neoplasms should be considered a
      possible side effect among patients receiving Fingolimod.

PMID- 29195115
TI  - Effect of dietary carbohydrates and time of year on ACTH and cortisol
      concentrations in adult and aged horses.
AB  - Diagnosis of equine pituitary pars intermedia dysfunction (PPID) remains a
      challenge as multiple factors (stress, exercise, and time of year) influence ACTH
      and cortisol concentrations. To assess endocrine status in a study designed to
      evaluate the effects of age and diet on glucose and insulin dynamics, we
      performed thyrotropin-releasing hormone (TRH) stimulation tests and overnight
      dexamethasone suppression tests in March, May, August, and October on 16 healthy
      Thoroughbred and Standardbred mares and geldings. Horses were grouped by age:
      adult (mean +/- SD; 8.8 +/- 2.9 yr; n = 8) and aged (20.6 +/- 2.1 yr; n = 8).
      None of the horses showed clinical signs (hypertrichosis, regional adiposity,
      skeletal muscle atrophy, lethargy) of pituitary pars intermedia dysfunction.
      Horses were randomly assigned to groups of 4, blocked for age, and fed grass hay
      plus 4 isocaloric concentrate diets (control, starch-rich, fiber-rich, and sugar
      rich) using a balanced Latin square design. Data were analyzed using a
      multivariable linear mixed regression model. Baseline ACTH was significantly
      higher in aged horses (mean +/- standard error of the mean; 60.0 +/- 10.7 pg/mL)
      adapted to the starch-rich diet compared to adult horses (15.7 +/- 12.0 pg/mL) on
      the same diet (P = 0.017). After controlling for age and diet, baseline ACTH
      concentrations were significantly increased in October (57.7 +/- 7.1 pg/mL)
      compared to March (13.2 +/- 7.1 pg/mL; P < 0.001), May (12.4 +/- 7.1 pg/mL; P <
      0.001), and August (24.2 +/- 7.1 pg/mL; P < 0.001), whereas post-TRH ACTH was
      higher in August (376.6 +/- 57.6 pg/mL) and October (370.9 +/- 57.5 pg/mL)
      compared to March (101.9 +/- 57.3 pg/mL; P < 0.001) and May (74.5 +/- 57.1 pg/mL;
      P < 0.001). Aged horses had significantly higher post-dexamethasone cortisol on
      the starch-rich diet (0.6 +/- 0.1 MUg/dL) compared to the sugar-rich diet (0.2 +/
      0.1 MUg/dL; P = 0.021). Post-dexamethasone cortisol was significantly higher in
      October (0.6 +/- 0.1 MUg/dL) compared to March (0.3 +/- 0.1 MUg/dL; P = 0.005),
      May (0.2 +/- 0.1 MUg/dL; P < 0.001), and August (0.3 +/- 0.1 MUg/dL; P = 0.004).
      Breed did not influence ACTH or cortisol measurements. In conclusion, in addition
      to age and time of year, diet is a potential confounder as animals on a starch
      rich diet may be incorrectly diagnosed with pituitary pars intermedia
      dysfunction.

PMID- 29195116
TI  - PD-L1 status does not predict the outcome of BRAF inhibitor therapy in metastatic
      melanoma.
AB  - BACKGROUND: Targeted therapies with BRAF plus MEK inhibitors (BRAFi; MEKi)
      represent the major treatment strategy for patients with BRAF-mutated metastatic
      melanoma (MM). Previous analyses suggested a correlation between programmed death
      ligand 1 (PD-L1) expression in tumour tissues and the outcome of targeted
      therapies. This study investigated PD-L1 as a potential predictive biomarker of
      BRAFi-based targeted therapies in MM patients. PATIENTS AND METHODS: We analysed
      two independent cohorts of BRAF V600-mutated MM patients undergoing BRAFi-based
      therapies for PD-L1 expression in pre-treatment tumour tissues. The oligocentre
      cohort 1 included 83 patients whose tumour tissues were analysed retrospectively
      with the anti-PD-L1 antibody clone E1L3N. The multicentre cohort 2 included 58
      patients whose tumour tissues were analysed prospectively within the framework of
      the "Registry of the Arbeitsgemeinschaft Dermatologische Onkologie" (ADOREG) and
      "Tissue Registry in Melanoma" (TRIM) project using the anti-PD-L1 antibody clone
      28-8. RESULTS: PD-L1 expression in pre-treatment tumour tissue did not correlate
      with response or survival to BRAFi-based therapies in both MM patient cohorts.
      This finding was not influenced by retrospective versus prospective
      immunohistochemistry analyses, oligocentre versus multicentre cohorts or the
      different anti-PD-L1 antibody clones used. In cohort 1, PD-L1 positivity was
      detected in tumour tissue of 41.0% and 18.1% of patients (cut-off 1% and 5%,
      respectively). In cohort 2, 58.6% and 39.7% of patients showed PD-L1 positivity
      (cut-off 1% and 5%, respectively). CONCLUSION: In two independent cohorts
      including a total of 141 MM patients, PD-L1 expression in tumour tissue did not
      correlate with the outcome of BRAFi-based treatment. Therefore, PD-L1 cannot be
      recommended for the use as a predictive biomarker of BRAFi-based therapy in BRAF
      V600-mutated MM.

PMID- 29195117
TI  - Surgical treatment options following chemotherapy plus cetuximab or bevacizumab
      in metastatic colorectal cancer-central evaluation of FIRE-3.
AB  - BACKGROUND: The FIRE-3 trial investigated combination chemotherapy plus either
      cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer
      (mCRC) not scheduled for upfront surgery. We aimed to determine the number of
      patients who present with potentially resectable disease during systemic first
      line therapy and to compare the findings with study reports concerning resections
      and outcome. PATIENTS AND METHODS: This evaluation of 448 patients was performed
      as central review blinded for treatment, other reviewers' evaluations and
      conducted interventions. Resectability was defined if at least 50% of the
      reviewers recommended surgical-based intervention. Overall survival was assessed
      by Kaplan-Meier method. RESULTS: Resectability increased from 22% (97/448) at
      baseline before treatment to 53% (238/448) at best response (P < 0.001), compared
      with an actual secondary resection rate for metastases of 16% (72/448). At
      baseline (23% versus 20%) and best response (53% versus 53%), potential
      resectability of metastases in this molecular unselected population was similar
      in cetuximab-treated patients versus bevacizumab-treated patients and not limited
      to patients with one-organ disease. The actual resection rate of metastases was
      significantly associated with treatment setting (P = 0.02; university hospital
      versus hospital/practice). Overall survival was 51.3 months (95% confidence
      interval [CI] 35.9-66.7) in patients with resectable disease who received
      surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease
      without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable
      disease (P < 0.001). CONCLUSIONS: Our findings illustrate the potential for
      conversion to resectability in mCRC, certain reluctance towards metastatic
      resections in clinical practice and the need for pre-planned and continuous
      evaluation for metastatic resection in high-volume centres. CLINICALTRIALS. GOV
      IDENTIFIER: NCT00433927.

PMID- 29195118
TI  - Deciphering p53 signaling in tumor suppression.
AB  - The p53 transcription factor is mutated in over half of human cancers, and p53
      null mice are highly predisposed to cancer, highlighting p53s essential role in
      tumor suppression. Studies in mouse models have revealed that p53 cell cycle
      arrest and apoptosis responses to acute DNA damage signals are dispensable for
      tumor suppression, prompting a search for new mechanisms underlying p53-mediated
      cancer suppression. p53 responds to other types of stress signals and regulates a
      host other cellular processes, including maintenance of genomic stability,
      metabolism, stemness, non-apoptotic cell death, migration/invasion, and cell
      signaling, any or all of which could be fundamental for suppressing
      carcinogenesis. The ability of p53 to govern numerous transcriptional programs
      and cellular functions likely explains its potent tumor suppressor activity.

PMID- 29195119
TI  - Interleukin 11 is upregulated in preeclampsia and leads to inflammation and
      preeclampsia features in mice.
AB  - Preeclampsia is a dangerous pregnancy complication, which is often associated
      with fetal growth restriction and can have serious life-long effects for both
      mother and baby. While the establishment of the placenta in the first trimester
      is the sentinel event in the development of preeclampsia little is known of the
      critical mechanisms of placentation that lead to the syndrome. Locally produced
      inflammatory cytokines are thought to play a role in the development of
      preeclampsia. This review summarizes the evidence that interleukin 11 is
      dysregulated in preeclampsia and contributes to the initiation of preeclampsia
      via effects on placentation. It discusses the benefits and drawbacks of targeting
      IL11 as a novel treatment option for preeclampsia.

PMID- 29195120
TI  - Advances in cellulosic conversion to fuels: engineering yeasts for cellulosic
      bioethanol and biodiesel production.
AB  - Cellulosic fuels are expected to have great potential industrial applications in
      the near future, but they still face technical challenges to become cost
      competitive fuels, thus presenting many opportunities for improvement. The
      economical production of viable biofuels requires metabolic engineering of
      microbial platforms to convert cellulosic biomass into biofuels with high titers
      and yields. Fortunately, integrating traditional and novel engineering strategies
      with advanced engineering toolboxes has allowed the development of more robust
      microbial platforms, thus expanding substrate ranges. This review highlights
      recent trends in the metabolic engineering of microbial platforms, such as the
      industrial yeasts Saccharomyces cerevisiae and Yarrowia lipolytica, for the
      production of renewable fuels.

PMID- 29195121
TI  - Timing of CRISPR/Cas9-related mRNA microinjection after activation as an
      important factor affecting genome editing efficiency in porcine oocytes.
AB  - Recently, successful one-step genome editing by microinjection of CRISPR/Cas9
      related mRNA components into the porcine zygote has been described. Given the
      relatively long gestational period and the high cost of housing swine, the
      establishment of an effective microinjection-based porcine genome editing method
      is urgently required. Previously, we have attempted to disrupt a gene encoding
      alpha-1,3-galactosyltransferase (GGTA1), which synthesizes the alpha-Gal epitope,
      by microinjecting CRISPR/Cas9-related nucleic acids and enhanced green
      fluorescent protein (EGFP) mRNA into porcine oocytes immediately after electrical
      activation. We found that genome editing was indeed induced, although the
      resulting blastocysts were mosaic and the frequency of modified cells appeared to
      be low (50%). To improve genome editing efficiency in porcine oocytes,
      cytoplasmic injection was performed 6 h after electrical activation, a stage
      wherein the pronucleus is formed. The developing blastocysts exhibited higher
      levels of EGFP. Furthermore, the T7 endonuclease 1 assay and subsequent
      sequencing demonstrated that these embryos exhibited increased genome editing
      efficiencies (69%), although a high degree of mosaicism for the induced mutation
      was still observed. Single blastocyst-based cytochemical staining with
      fluorescently labeled isolectin BS-I-B4 also confirmed this mosaicism. Thus, the
      development of a technique that avoids or reduces such mosaicism would be a key
      factor for efficient knock out piglet production via microinjection.

PMID- 29195122
TI  - Norwegian monitoring (1990-2015) of the marine environment around the sunken
      nuclear submarine Komsomolets.
AB  - Norway has monitored the marine environment around the sunken Russian nuclear
      submarine Komsomolets since 1990. This study presents an overview of 25 years of
      Norwegian monitoring data (1990-2015). Komsomolets sank in 1989 at a depth of
      1680 m in the Norwegian Sea while carrying two nuclear torpedoes in its armament.
      Subsequent Soviet and Russian expeditions to Komsomolets have shown that releases
      from the reactor have occurred and that the submarine has suffered considerable
      damage to its hulls. Norwegian monitoring detected 134Cs in surface sediments
      around Komsomolets in 1993 and 1994 and elevated activity concentrations of 137Cs
      in bottom seawater between 1991 and 1993. Since then and up to 2015, no increased
      activity concentrations of radionuclides above values typical for the Norwegian
      Sea have been observed in any environmental sample collected by Norwegian
      monitoring. In 2013 and 2015, Norwegian monitoring was carried out using an
      acoustic transponder on the sampling gear that allowed samples to be collected at
      precise locations, ~20 m from the hull of Komsomolets. The observed
      238Pu/239,240Pu activity ratios and 240Pu/239Pu atom ratios in surface sediments
      sampled close to Komsomolets in 2013 did not indicate any releases of Pu isotopes
      from reactor or the torpedo warheads. Rather, these values probably reflect the
      overprinting of global fallout ratios with fluxes of these Pu isotopes from long
      range transport of authorised discharges from nuclear reprocessing facilities in
      Northern Europe. However, due to the depth at which Komsomolets lies, the
      collection of seawater and sediment samples in the immediate area around the
      submarine using traditional sampling techniques from surface vessels is not
      possible, even with the use of acoustic transponders. Further monitoring is
      required in order to have a clear understanding of the current status of
      Komsomolets as a potential source of radioactive contamination to the Norwegian
      marine environment. Such monitoring should involve the use of ROVs or
      submersibles in order to obtain samples next to and within the different
      compartments of the submarine.

PMID- 29195123
TI  - Uranium(VI) sorption complexes on silica in the presence of calcium and
      carbonate.
AB  - Uranium sorption on minerals and related solids depends to a large degree on its
      aqueous speciation. The present work attempts to understand the U(VI) sorption
      behavior on silica under environmentally relevant conditions, i.e. at neutral to
      weakly alkaline pH and in the presence of dissolved calcium and carbonate. Under
      these conditions, Ca(UO2)(CO3)32- and Ca2(UO2)(CO3)3(aq) complexes emerge as the
      dominant aqueous U(VI) species. The U(VI) sorption affinity was measured as a
      function of contact time, solution pH, and humic acid. The U(VI) sorption
      decreased with increase of pH and was not affected by the addition of 50 mg/L
      humic acid. On the other hand, nitric acid was more effective than EDTA and
      carbonate at desorbing U(VI). Generally, the U(VI) sorbed on silica at neutral pH
      was less readily desorbed than that sorbed at higher pH values. Therefore, the
      U(VI) complex favorably sorbed on silica at the neutral pH is more strongly bound
      to the silica surface than that sorbed at higher pH values. Time-resolved laser
      fluorescence spectroscopy confirmed the results of the batch sorption experiments
      and revealed the presence of two surface U(VI) complexes with fluorescence
      lifetimes 251 +/- 8 MUs and 807 +/- 24 MUs.

PMID- 29195124
TI  - Corrigendum to "The external gate of the human and Drosophila serotonin
      transporters requires a basic/acidic amino acid pair for 3,4
      methylenedioxymethamphetamine (MDMA) translocation and the induction of substrate
      efflux" [Biochem. Pharmacol. 120 (2016) 46-55].

PMID- 29195125
TI  - Effects of continuation electroconvulsive therapy on quality of life in elderly
      depressed patients: A randomized clinical trial.
AB  - We examined whether electroconvulsive therapy (ECT) plus medications ("STABLE +
      PHARM" group) had superior HRQOL compared with medications alone ("PHARM" group)
      as continuation strategy after successful acute right unilateral ECT for major
      depressive disorder (MDD). We hypothesized that scores from the Medical Outcomes
      Study Short Form-36 (SF-36) would be higher during continuation treatment in the
      "STABLE + PHARM" group versus the "PHARM" group. The overall study design was
      called "Prolonging Remission in Depressed Elderly" (PRIDE). Remitters to the
      acute course of ECT were re-consented to enter a 6 month RCT of "STABLE + PHARM"
      versus "PHARM". Measures of depressive symptoms and cognitive function were
      completed by blind raters; SF-36 measurements were patient self-report every 4
      weeks. Participants were 120 patients >60 years old. Patients with dementia,
      schizophrenia, bipolar disorder, or substance abuse were excluded. The "PHARM"
      group received venlafaxine and lithium. The "STABLE + PHARM" received the same
      medications, plus 4 weekly outpatient ECT sessions, with additional ECT session
      as needed. Participants were mostly female (61.7%) with a mean age of 70.5 +/-
      7.2 years. "STABLE + PHARM" patients received 4.5 +/- 2.5 ECT sessions during
      Phase 2. "STABLE + PHARM" group had 7 point advantage (3.5-10.4, 95% CI) for
      Physical Component Score of SF-36 (P < 0.0001), and 8.2 point advantage (4.2
      12.2, 95% CI) for Mental Component Score (P < 0.0001). Additional ECT resulted in
      overall net health benefit. Consideration should be given to administration of
      additional ECT to prevent relapse during the continuation phase of treatment of
      MDD. CLINICAL TRIALS.GOV: NCT01028508.

PMID- 29195128
TI  - Monitoring city wide patterns of cycling safety.
AB  - Many cities are making significant financial investments in cycling
      infrastructure with the aim of making cycling safer for riders of all ages and
      abilities. Methods for evaluating cycling safety tend to summarize average change
      for a city or emphasize change on a single road segment. Few spatially explicit
      approaches are available to evaluate how patterns of safety change throughout a
      city due to cycling infrastructure investments or other changes. Our goal is to
      demonstrate a method for monitoring changes in the spatial-temporal distribution
      of cycling incidents across a city. Using cycling incident data provided by the
      Insurance Corporation of British Columbia, we first compare planar versus network
      constrained kernel density estimation for visualizing incident intensity across
      the street network of Vancouver, Canada. Second, we apply a change detection
      algorithm explicitly designed for detecting statistically significant change in
      kernel density estimates. The utility of network kernel density change detection
      is demonstrated through the comparison of cycling incident densities following
      the construction of two cycle tracks in the downtown core of Vancouver. The
      methods developed and demonstrated for this study provide city planners,
      transportation engineers and researchers a means of monitoring city-wide change
      in the intensity of cycling incidents following enhancements to cycling
      infrastructure or other significant changes to the transportation network.

PMID- 29195126
TI  - Stimulation of Interferon-Stimulated Gene 20 by Thyroid Hormone Enhances
      Angiogenesis in Liver Cancer.
AB  - Thyroid hormone, 3,3',5-triiodo-l-thyronine (T3), mediates several physiological
      processes, including embryonic development, cellular differentiation and cell
      proliferation, via binding to its nuclear thyroid receptors (TR). Previous
      microarray and Chromatin immunoprecipitation (ChIP)-on-ChIP analyses have
      revealed that interferon-stimulated gene 20 kDa (ISG20), an exoribonuclease
      involved in the antiviral function of interferon, is up-regulated by T3 in HepG2
      TR cells. However, the underlying mechanisms of ISG20 action in tumor progression
      remain unknown to date. Here, we verified induction of ISG20 mRNA and protein
      expression by T3 in HepG2-TR cells. Based on the ChIP-on-ChIP database, potential
      thyroid hormone responsive element of the ISG20 promoter region was predicted,
      and the result confirmed with the ChIP assay. Functional assays showed that
      forced expression of ISG20 leads to significant promotion of metastasis and
      angiogenesis, both in vitro and in vivo. Furthermore, the angiogenic-related
      protein, interleukin-8 (IL-8), was up-regulated through a T3-mediated increase in
      ISG20, as determined using a human angiogenesis array kit. Induction of IL-8
      signaling activated the p-JAK2/p-STAT3 pathway, in turn, leading to promotion of
      tumor metastasis and angiogenesis. Furthermore, ISG20 overexpression in
      hepatocellular carcinoma (HCC) specimens was positively correlated with clinical
      parameters, including vascular invasion, alpha-fetoprotein and tumor size. Higher
      ISG20 expression was significantly correlated with poorer recurrence-free
      survival in HCC patients. Our results collectively indicate higher TR-dependent
      expression of ISG20 in a subset of HCC, supporting an oncogenic role in HCC
      progression.

PMID- 29195127
TI  - Rapamycin Synergizes with Cisplatin in Antiendometrial Cancer Activation by
      Improving IL-27-Stimulated Cytotoxicity of NK Cells.
AB  - Natural killer (NK) cell function is critical for controlling initial tumor
      growth and determining chemosensitivity of the tumor. A synergistic relationship
      between rapamycin and cisplatin in uterine endometrial cancer (UEC) in vitro has
      been reported, but the mechanism and the combined therapeutic strategy for
      endometrial cancer (EC) are still unknown. We found a positive correlation
      between the level of IL-27 and the differentiated stage of UEC. The increase of
      IL-27 in uterine endometrial cancer cell (UECC) lines (Ishikawa, RL95-2 and KLE)
      led to a high cytotoxic activity of NK cells to UECC in the co-culture system.
      Exposure with rapamycin enhanced the cytotoxicity of NK cells by upregulating the
      expression of IL-27 in UECC and IL-27 receptors (IL-27Rs: WSX-1 and gp130) on NK
      cells and further restricted the growth of UEC in Ishikawa-xenografted nude mice.
      In addition, treatment with rapamycin resulted in an increased autophagy level of
      UECC, and IL-27 enhanced this ability of rapamycin. Cisplatin-mediated NK cells'
      cytotoxic activity and anti-UEC activation were independent of IL-27; however,
      the combination of rapamycin and cisplatin led to a higher cytotoxic activity of
      NK cells, smaller UEC volume and longer survival rate in vivo. These results
      suggest that rapamycin and cisplatin synergistically activate the cytotoxicity of
      NK cells and inhibit the progression of UEC in both an IL-27-dependent and 
      independent manner. This provides a scientific basis for potential rapamycin
      cisplatin combined therapeutic strategies targeted to UEC, especially for the
      patients with low differentiated stage or abnormally low level of IL-27.

PMID- 29195129
TI  - Risk factors for crash involvement in older motorcycle riders.
AB  - A prospective cohort study was conducted to identify risk and protective factors
      for crash involvement in older motorcyclists. Over a 1-year study period from
      August 2013 to July 2014, study participants were recruited from local community
      centers of five cities in Taiwan. People aged >=60 years who rode a motorcycle at
      least once per week were eligible and were invited to participate in the study.
      Among 256 older riders who completed the baseline assessment and at least one of
      the four follow-up assessments, 79 (33.7%) experienced a motorcycle crash over
      the study period. Results of the proportional hazards model showed that after
      controlling for age, gender, and riding distance, older riders who had sustained
      hearing impairment (hazard ratio (HR)=2.58; 95% confidence interval (CI), 1.30
      5.15), rode a motorcycle at speeds of >=41km/h (HR=2.31; 95% CI, 1.26-4.23), and
      had experienced a motorcycle crash in the past year (HR=1.81; 95% CI, 1.06-3.09)
      were more likely to be involved in a crash, compared to their counterparts.
      Conversely, older riders who were obese (HR=0.43; 95% CI, 0.22-0.82) were less
      likely to be involved in a crash than those with a normal weight, while longer
      functional reach distances (HR=0.96; 95% CI, 0.93-0.99) and higher Tinetti
      balance scores (HR=0.79; 95% CI, 0.69-0.91) were associated with a reduced risk
      of crash involvement. Among older people riding a motorcycle as their primary
      source of transportation, several factors associated with the occurrence of
      motorcycle crashes were identified. Restrictions and modifications of these risk
      factors may help design effective safety interventions for reducing crash and
      injury risks of this increasing riding population.

PMID- 29195130
TI  - Analyzing crash frequency in freeway tunnels: A correlated random parameters
      approach.
AB  - The majority of past road safety studies focused on open road segments while only
      a few focused on tunnels. Moreover, the past tunnel studies produced some
      inconsistent results about the safety effects of the traffic patterns, the tunnel
      design, and the pavement conditions. The effects of these conditions therefore
      remain unknown, especially for freeway tunnels in China. The study presented in
      this paper investigated the safety effects of these various factors utilizing a
      four-year period (2009-2012) of data as well as three models: 1) a random effects
      negative binomial model (RENB), 2) an uncorrelated random parameters negative
      binomial model (URPNB), and 3) a correlated random parameters negative binomial
      model (CRPNB). Of these three, the results showed that the CRPNB model provided
      better goodness-of-fit and offered more insights into the factors that contribute
      to tunnel safety. The CRPNB was not only able to allocate the part of the
      otherwise unobserved heterogeneity to the individual model parameters but also
      was able to estimate the cross-correlations between these parameters.
      Furthermore, the study results showed that traffic volume, tunnel length,
      proportion of heavy trucks, curvature, and pavement rutting were associated with
      higher frequencies of traffic crashes, while the distance to the tunnel wall,
      distance to the adjacent tunnel, distress ratio, International Roughness Index
      (IRI), and friction coefficient were associated with lower crash frequencies. In
      addition, the effects of the heterogeneity of the proportion of heavy trucks, the
      curvature, the rutting depth, and the friction coefficient were identified and
      their inter-correlations were analyzed.

PMID- 29195131
TI  - Motor priming by movement observation with contralateral concurrent action
      execution.
AB  - In the present study, the influence of simultaneous action execution on motor
      priming was investigated during movement observation using a simple-reaction
      task. Although previous studies have reported various effects of priming on motor
      performance, it has not yet been clarified how an additional source conveying
      kinetic information would modulate the priming effects. In the experiment,
      participants were asked to respond to an auditory cue by flexing their wrist
      while observing a line movement, which was slowly swinging like an inverted
      pendulum. In addition to the observation of line movement, the participants
      executed wrist flexion-extension actions synchronizing with line movement. The
      hand involved in pre-response wrist action varied with the priming condition: no
      movement execution (observation only), contralateral hand, and ipsilateral hand.
      In the contralateral condition, the stimulus-response congruency of movement
      direction was conflicted depending on the frame of reference (visual vs.
      anatomical coordinates). We found that all three priming conditions produced the
      compatibility effect, and the effect size did not differ between them.
      Importantly, in the contralateral condition, participants responded faster when
      the direction of line movement was congruent with the response movement in the
      anatomical coordinates. That is, the reaction time was shorter when pre-response
      action execution was in the flexion phase, even though the direction of observed
      movement and the response action were incongruent from the participants' view.
      These results suggest that kinetic information has a great contribution to the
      motor priming system, which can reverse the vision-based compatibility effect.

PMID- 29195132
TI  - Lycopene mitigates beta-amyloid induced inflammatory response and inhibits NF
      kappaB signaling at the choroid plexus in early stages of Alzheimer's disease
      rats.
AB  - The choroid plexus is able to modulate the cognitive function, through changes in
      the neuroinflammatory response and in brain immune surveillance. However, whether
      lycopene is involved in inflammatory responses at the choroid plexus in the early
      stages of Alzheimer's disease, and its molecular underpinnings are elusive. In
      this rat study, lycopene was used to investigate its protective effects on
      inflammation caused by beta-amyloid. We characterized the learning and memory
      abilities, cytokine profiles of circulating TNF-alpha, IL-1beta and IL-6beta in
      the serum and the expressions of Toll like receptor 4 and nuclear factor-kappaB
      p65 mRNA and protein at the choroid plexus. The results showed that functional
      deficits of learning and memory in lycopene treatment groups were significantly
      improved compared to the control group without lycopene treatment in water maze
      test. The levels of serum TNF-alpha, IL-1beta and IL-6beta were significantly
      increased, and the expressions of TLR4 and NF-kappaB p65 mRNA and protein at the
      choroid plexus were up-regulated, indicating inflammation response was initiated
      following administration of Abeta1-42. After intragastric pretreatment with
      lycopene, inflammatory cytokines were significantly reduced and lycopene also
      reversed the Abeta1-42 induced up-regulation of TLR4 and NF-kappaB p65 mRNA and
      protein expressions at the choroid plexus. These results provided a novel
      evidence that lycopene significantly improved cognitive deficits and were
      accompanied by the attenuation of inflammatory injury via blocking the activation
      of NF-kappaB p65 and TLR4 expressions and production of cytokines, thereby
      endorsing its usefulness for diminishing beta-amyloid deposition in the
      hippocampus tissues.

PMID- 29195134
TI  - Developing cellulosic waste products as platform chemicals: protecting group
      chemistry of alpha-glucoisosaccharinic acid.
AB  - Alpha and beta-glucoisosaccharinic acids ((2S,4S)-2,4,5-trihydroxy-2
      (hydroxymethyl)pentanoic acid and (2R,4S)-2,4,5-trihydroxy-2
      (hydroxymethyl)pentanoic acid) which are produced when cellulosic materials are
      treated with aqueous alkali are potentially valuable platform chemicals. Their
      highly functionalised carbon skeleton, with fixed chirality at C-2 and C-4, makes
      them ideal starting materials for use in synthesis. In order to assess the
      potential of these saccharinic acids as platform chemicals we have explored the
      protecting group chemistry of the lactone form of alpha-glucoisosaccharinic acid
      (alpha-GISAL). We report here the use of single and multiple step reaction
      pathways leading to the regioselective protection of the three different hydroxyl
      groups of alpha-GISAL. We report strategies for protecting the three different
      hydroxyl groups individually or in pairs. We also report the synthesis of a range
      of tri-O-protected alpha-GISAL derivatives where a number of the products contain
      orthogonal protecting groups.

PMID- 29195133
TI  - Effects of fish oils on ex vivo B-cell responses of obese subjects upon BCR/TLR
      stimulation: a pilot study.
AB  - The long-chain n-3 polyunsaturated fatty acids (LC-PUFAs) eicosapentaenoic (EPA)
      and docosahexaenoic acid (DHA) in fish oil have immunomodulatory properties. B
      cells are a poorly studied target of EPA/DHA in humans. Therefore, in this pilot
      study, we tested how n-3 LC-PUFAs influence B-cell responses of obese humans.
      Obese men and women were assigned to consume four 1-g capsules per day of olive
      oil (OO, n=12), fish oil (FO, n=12) concentrate or high-DHA-FO concentrate (n=10)
      for 12 weeks in a parallel design. Relative to baseline, FO (n=9) lowered the
      percentage of circulating memory and plasma B cells, whereas the other
      supplements had no effect. There were no postintervention differences between the
      three supplements. Next, ex vivo B-cell cytokines were assayed after stimulation
      of Toll-like receptors (TLRs) and/or the B-cell receptor (BCR) to determine if
      the effects of n-3 LC-PUFAs were pathway-dependent. B-cell IL-10 and TNFalpha
      secretion was respectively increased with high DHA-FO (n=10), relative to
      baseline, with respective TLR9 and TLR9+BCR stimulation. OO (n=12) and FO (n=12)
      had no influence on B-cell cytokines compared to baseline, and there were no
      differences in postintervention cytokine levels between treatment groups.
      Finally, ex vivo antibody levels were assayed with FO (n=7) after TLR9+BCR
      stimulation. Compared to baseline, FO lowered IgM but not IgG levels accompanied
      by select modifications to the plasma lipidome. Altogether, the results suggest
      that n-3 LC-PUFAs could modulate B-cell activity in humans, which will require
      further testing in a larger cohort.

PMID- 29195135
TI  - Urinary metabolites of organophosphate esters: Concentrations and age trends in
      Australian children.
AB  - There is growing concern around the use of organophosphate esters (OPEs) due to
      their suspected reproductive toxicity, carcinogenicity, and neurotoxicity. OPEs
      are used as flame retardants and plasticizers, and due to their extensive
      application in consumer products, are found globally in the indoor environment.
      Early life exposure to OPEs is an important risk factor for children's health,
      but poorly understood. To study age and sex trends of OPE exposures in infants
      and young children, we collected, pooled, and analysed urine samples from
      children aged 0-5years from Queensland, Australia for 9 parent OPEs and 11
      metabolites. Individual urine samples (n=400) were stratified by age and sex, and
      combined into 20 pools. Three individual breast milk samples were also analysed
      to provide a preliminary estimate on the contribution of breast milk to the
      intake of OPEs. Bis(1-chloroisopropyl) phosphate (BCIPP), 1-hydroxy-2-propyl
      bis(1-chloro-2-propyl) phosphate (BCIPHIPP), bis(1,3-dichloroisopropyl) phosphate
      (BDCIPP), dibutyl phosphate (DBP), diphenyl phosphate (DPHP), bis(2-butoxyethyl)
      phosphate (BBOEP), bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate (3OH
      TBOEP), and bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) were detected in
      all urine samples, followed by bis(methylphenyl) phosphate (80%), and bis(2
      ethylhexyl) phosphate (BEHP, 20%), and bis(2-chloroethyl) phosphate (BCEP, 15%).
      Concentrations of tris(2-chloroethyl) phosphate (TCEP), BCEP, tris(2-ethylhexyl)
      phosphate (TEHP), and DBP decreased with age, while bis(methylphenyl) phosphate
      (BMPP) increased with age. Significantly higher concentrations of DPHP (p=0.039),
      and significantly lower concentrations of TEHP (p=0.006) were found in female
      samples compared to males. The estimated daily intakes (EDIs) via breastfeeding,
      were 4.6, 26 and 76ng/kg/day for TCEP, TBP and TEHP, respectively, and were
      higher than that via air and dust, suggesting higher exposure through consumption
      of breast milk.

PMID- 29195138
TI  - Mechanisms of head stability during gait initiation in young and older women: A
      neuro-mechanical analysis.
AB  - Decreased head stability has been reported in older women during locomotor
      transitions such as the initiation of gait. The aim of the study was to
      investigate the neuro-mechanical mechanisms underpinning head stabilisation in
      young and older women during gait initiation. Eleven young (23.1 +/- 1.1 yrs) and
      12 older (73.9 +/- 2.4 yrs) women initiated walking at comfortable speed while
      focussing on a fixed visual target at eye level. A stereophotogrammetric system
      was used to assess variability of angular displacement and RMS acceleration of
      the pelvis, trunk and head, and dynamic stability in the anteroposterior and
      mediolateral directions. Latency of muscle activation in the sternocleidomastoid,
      and upper and lower trunk muscles were determined by surface electromyography.
      Older displayed higher variability of head angular displacement, and a decreased
      ability to attenuate accelerations from trunk to head, compared to young in the
      anteroposterior but not mediolateral direction. Moreover, older displayed a
      delayed onset of sternocleidomastoid activation than young. In conclusion, the
      age-related decrease in head stability could be attributed to an impaired ability
      to attenuate accelerations from trunk to head along with delayed onset of neck
      muscles activation.

PMID- 29195136
TI  - Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in
      human macrophages.
AB  - Oxidized low-density lipoprotein (oxLDL) is a well-recognized proatherogenic
      particle that functions in atherosclerosis. In this study, we established
      conditions to generate human oxLDL, characterized according to the grade of lipid
      and protein oxidation, particle size and oxylipin content. The induction effect
      of the cellular proatherogenic response was assessed in foam cells by using an
      oxLDL-macrophage interaction model. Uptake of oxLDL, reactive oxygen species
      production and expression of oxLDL receptors (CD36, SR-A and LOX-1) were
      significantly increased in THP-1 macrophages. Analyses of 35 oxylipins revealed
      that isoprostanes (IsoP) and prostaglandins (PGs) derived from the oxidation of
      arachidonic, dihomo gamma-linolenic and eicosapentaenoic acids were strongly and
      significantly induced in macrophages stimulated with oxLDL. Importantly, the main
      metabolites responsible for the THP1-macrophage response to oxLDL exposure were
      the oxidative stress markers 5-epi-5-F2t-IsoP, 15-E1t-IsoP, 8-F3t-IsoP and 15
      keto-15-F2t-IsoP as well as inflammatory markers PGDM, 17-trans-PGF3alpha, and
      11beta-PGF2alpha, all of which are reported here, for the first time, to function
      in the interaction of oxLDL with THP-1 macrophages. By contrast, a salvage
      pathway mediated by anti-inflammatory PGs (PGE1 and 17-trans-PGF3alpha) was also
      identified, suggesting a response to oxLDL-induced injury. In conclusion, when
      THP-1 macrophages were treated with oxLDL, a specific induction of biomarkers
      related to oxidative stress and inflammation was triggered. This work contributes
      to our understanding of initial atherogenic events mediated by oxLDL-macrophage
      interactions and helps to generate new approaches for their modulation.

PMID- 29195137
TI  - The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced
      vascular dysfunction in mice.
AB  - AIM: NADPH oxidases are important sources of reactive oxygen species (ROS).
      Several Nox homologues are present together in the vascular system but whether
      they exhibit crosstalk at the activity level is unknown. To address this, vessel
      function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1
      and a p47phox-NoxO1-double knockout were studied under normal condition and
      during streptozotocin-induced diabetes. RESULTS: In the mouse aorta, mRNA
      expression for NoxO1 was predominant in smooth muscle and endothelial cells,
      whereas p47phox was markedly expressed in adventitial cells comprising leukocytes
      and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in
      lower basal blood pressure. Deletion of any of the two subunits also prevented
      diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive
      Analysis of cDNA ends) identified substantial gene expression differences between
      the mouse lines and in response to diabetes. Deletion of p47phox induced
      inflammatory activation with increased markers of myeloid cells and cytokine and
      chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated
      interferon gamma signature and reduced expression of genes related to antigen
      presentation. This aspect was also reflected by a reduced number of circulating
      lymphocytes in NoxO1-/- mice. INNOVATION AND CONCLUSION: ROS production
      stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and
      maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute
      each other despite their similar effect on vascular function. Deletion of NoxO1
      induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited
      a hyper-inflammatory response.

PMID- 29195139
TI  - Electron-beam broadening in amorphous carbon films in low-energy scanning
      transmission electron microscopy.
AB  - Resolution in scanning transmission electron microscopy (STEM) is ultimately
      limited by the diameter of the electron beam. The electron beam diameter is not
      only determined by the properties of the condenser lens system but also by
      electron scattering in the specimen which leads to electron-beam broadening and
      degradation of the resolution with increasing specimen thickness. In this work we
      introduce a new method to measure electron-beam broadening which is based on STEM
      imaging with a multi-segmented STEM detector. We focus on STEM at low electron
      energies between 10 and 30 keV and use an amorphous carbon film with known
      thickness as test object. The experimental results are compared with calculated
      beam diameters using different analytical models and Monte-Carlo simulations. We
      find excellent agreement of the experimental data with the recently published
      model by Gauvin and Rudinsky [1] for small t/lambdael (thickness to elastic mean
      free path) values which are considered in our study.

PMID- 29195140
TI  - Are the decrease in circulating anti-alpha1,3-Gal IgG and the lower content of
      galactosyl transferase A1 in the microbiota of patients with multiple sclerosis a
      novel environmental risk factor for the disease?
AB  - The etiology of multiple sclerosis (MS), particularly the environmental component
      of the disease, remains speculative. Recent reports have suggested that
      alterations in the gut microbiota of MS patients could contribute to the etiology
      or pathophysiology of the disease. In this Viewpoint, using PICRUSt (Phylogenetic
      Investigation of Communities by Reconstruction of Unobserved States) to infer the
      functional content of the gut microbiota, we show that the gut microbiota of MS
      patients is characterized by a significant decrease in the relative abundance of
      the enzyme EC 2.4.1.87, which corresponds to the GGTA1 gene (which codes for the
      alpha1,3-Gal epitope and is lacking in humans), against which MS patients also
      have low levels of IgG antibodies. The decrease in circulating anti-alpha1,3-Gal
      IgG and lower content of galactosyl transferase A1 in the microbiota of patients
      with multiple sclerosis could be a novel environmental risk factor for the
      disease.

PMID- 29195142
TI  - Quantification of glycerophospholipids and sphingomyelin in human milk and infant
      formula by high performance liquid chromatography coupled with mass spectrometer
      detector.
AB  - Phospholipids and sphingomyelin have a central role in infant nutrition,
      phospholipid acting as a nutrient carrier of long chain polyunsaturated fatty
      acids and sphingomyelin having an important role in cognitive function. However,
      analytical methods to precisely characterize and quantify these compounds in
      maternal milk are needed. Phospholipids and sphingomyelin were extracted using
      chloroform and methanol and separated on Polaris 3 Si column 250*2.0mm from
      Varian and analyzed by high performance liquid chromatography (HPLC) coupled with
      mass spectrometer detector (MS). The analytical method was validated and
      repeatability, intermediate reproducibility, and recovery values were calculated.
      The relative standard deviation of repeatability (CV(r)) and intermediate
      reproducibility (CV(iR)) values ranged between 2.3 and 7.2% and 9.5 and 17.8%,
      respectively and the recovery values between 96 and 109%. Finally, the validated
      method was tested on human milk samples and on infant formula which were analysed
      also by HPLC coupled with evaporative light scattering detector (ELSD). In human
      milk, sphingomyelin (9.28mg100mL-1) was the most abundant compound, followed by
      phosphatidylcholine (5.39mg100mL-1), phosphatidylethanolamine (2.85mg100mL-1) and
      phosphatidylinositol (1.82mg100mL-1).

PMID- 29195141
TI  - IL-17 is a protection effector against the adherent-invasive Escherichia coli in
      murine colitis.
AB  - Inflammatory bowel disease (IBD) is caused by aberrant immune responses to the
      gut microbiota. Among the gut microbiota, adherent-invasive Escherichia Coli
      (AIEC) is thought to be the pathogen through invading the intestinal epithelial
      cells and causing inflammation. IL-17 secretion increase, induced by enhanced
      bacterial adhesion to the intestine epithelium, could on one hand protect the
      mucosa, but on the other hand, over amount of IL-17 initializes inflammation
      reactions that in turn damages the mucosa. The relationship between IL-17 and
      AIEC is still unclear. In this study, we tried to elucidate the function of IL-17
      in AIEC-mediated colitis. Wild type (WT) and IL-17 knockout (IL-17 KO) mice were
      inoculated with AIEC strain E. coli LF82 and treated with dextran sodium sulphate
      (DSS). Histological examination of the colon was performed. Mucosa damage was
      assessed and scored. IL-22 and IL-17 in colon tissues were detected by ELISA,
      qPCR and immunohistochemistry methods. Transient AIEC colonization in IL-17 KO
      mice resulted in increased intestinal epithelial damage, systemic bacterial
      burden and mortality compared with WT controls. Moreover, IL-17 is required for
      the induction of IL-22 in the experimental animal models during AIEC strain E.
      coli LF82 colonization. These results indicate IL-17 plays a protective role in
      AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion.

PMID- 29195143
TI  - Metabolite identification and pharmacokinetic profiling of PP242, an ATP
      competitive inhibitor of mTOR using ultra high-performance liquid chromatography
      and mass spectrometry.
AB  - PP242 is a second generation novel selective ATP-competitive inhibitor of mTOR
      that displayed promising anti-cancer activity over several cancer types by
      inhibiting both the complexes of mTOR (mTORC1 and mTORC2). The purpose of this
      study is to identify the possible metabolites and to evaluate the pharmacokinetic
      profile of PP242 after a single oral administration to Sprague-Dawley (SD) rats.
      Two metabolites, including one phase I and one phase II, were identified by in
      vitro and in vivo studies using rat liver microsomes (RLMs) as well as rat
      plasma, urine and feces, respectively, through ultra high-performance liquid
      chromatography-linear ion trap quadrupole-orbitrap-mass spectrometry (UHPLC-LTQ
      Orbitrap-MS). The major biotransformation pathways of PP242 were hydroxylation
      and glucuronide conjugation. Additionally, a simple and rapid quantification
      method was developed and validated. The method recovery was within 79.7-84.6%,
      whereas the matrix effect was 78.1-96.0% in all three quality control (QC)
      concentrations (low, medium and high) including the LLOQ. Other parameters showed
      acceptable results according to the US food and drug administration (FDA)
      guidelines for bioanalytical method validation. Afterwards, pharmacokinetic
      parameters were evaluated in rat plasma by successfully applying the validated
      method using liquid chromatography-tandem mass spectrometry (LC-MS/MS). After a
      single oral administration at a dose of 5mg/kg, the maximum plasma concentration
      (Cmax) of PP242 was 0.17+/-0.08MUg/mL, while the elimination was moderately fast
      (T1/2: 172.18+/-45.54min). All of the obtained information on the metabolite
      identification and pharmacokinetic parameter elucidation could facilitate the
      further development of PP242.

PMID- 29195144
TI  - Quantification of amlodipine in dried blood spot samples by high performance
      liquid chromatography tandem mass spectrometry.
AB  - A sensitive and specific method, utilising high performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) was developed for the quantitative
      determination of amlodipine in dried blood spot (DBS) samples. Chromatographic
      separation was achieved using a Waters XBridge C18 column with gradient elution
      of a mixture of water and acetonitrile containing 0.1% formic acid (v/v).
      Amlodipine was quantified using a Waters Quattro Premier mass spectrometer
      coupled with an electro-spray ionization (ESI) source in positive ion mode. The
      MRM transitions of 408.9 m/z->238.1m/z and 408.9->294.0 m/z were used to quantify
      and qualify amlodipine, respectively. The method was validated across the
      concentration range of 0.5-30ng/mL by assessing specificity, sensitivity,
      linearity, precision, accuracy, recovery and matrix effect according to the Food
      and Drug Administration (FDA) guidelines. This method was also validated
      clinically within a large pharmacoepidemiological study in which amlodipine blood
      concentration was determined in patients who had been prescribed this medication.

PMID- 29195145
TI  - Simultaneous quantification of succinylacetone and nitisinone for therapeutic
      drug monitoring in the treatment of Tyrosinemia type 1.
AB  - We present a straightforward and robust method for simultaneous quantification of
      succinylacetone and nitisinone in plasma using LC-ESI-MS/MS. The method has been
      developed for routine therapeutic drug monitoring in hepatorenal tyrosinemia type
      1 (HT1) patients undergoing nitisinone treatment. Previous methods are based on
      separate analyses of succinylacetone and nitisinone, often using the potentially
      harmful compound hydrazine for derivatization of the former. In the present
      procedure, succinylacetone is derivatized in a single-step using butanolic HCl.
      Analyte extraction and sample clean-up is carried out by simple protein
      precipitation. The linear range for both analytes is 0.1 up to 125MUM, covering
      the vast majority of encountered levels in real-life samples. The sensitivity and
      limit of quantification allows measurement of succinylacetone in the
      therapeutical range for HT1 patients. Stability studies show that succinylacetone
      is highly sensitive to storage conditions, whereas nitisinone shows little to no
      degradation. Correct sample handling is therefore important for reliable results
      when monitoring succinylacetone concentrations.

PMID- 29195146
TI  - Fast and quantitative determination of saxitoxin and neosaxitoxin in urine by
      ultra performance liquid chromatography-triple quadrupole mass spectrometry based
      on the cleanup of solid phase extraction with hydrophilic interaction mechanism.
AB  - Saxitoxin (STX) and neosaxitoxin (NEO) are water-soluble toxins and their cleanup
      in bio-matrix is a hot topic but difficult problem. A fast and quantitative
      determination method for STX and NEO in urine was developed using ultra
      performance liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS)
      based on the cleanup of solid phase extraction (SPE) with hydrophilic interaction
      (HILIC) mechanism. Acetonitrile/methanol/water mixture was used to extract the
      toxins in urine. Polyamide (PA) was used as HILIC SPE material to clean the
      toxins in sample matrix. The limits of detection were 0.2ngmL-1 for STX and 1ngmL
      1 for NEO in urine. The linear ranges were 0.5ngmL-1-99.2ngmL-1 with the
      correlation coefficient of r=0.9992 for STX and 2.1ngmL-1-207ngmL-1 with r=0.997
      for NEO in urine matrix. The recoveries at three spiking levels were 81.5%-117%
      with the relative standard deviations (RSDs) of 5.4%-8.5% for STX and 89.0%-118%
      with the RSDs of 6.7%-9.1% for NEO. STX was found in all the 6 patients' urines
      while NEO was only found in one sample from an intoxication case.

PMID- 29195147
TI  - Young adult e-cigarette use outcome expectancies: Validity of a revised scale and
      a short scale.
AB  - The revised youth e-cigarette outcome expectancies measure adds new items
      informed by recent qualitative research with young adult e-cigarette users,
      especially in the domain of positive "smoking" experience. Positive "smoking"
      experience represents beliefs that use of e-cigarettes provides outcomes
      associated with a better "smoking" alternative: for example, an alternative that
      is more socially approved, more suitable for indoor use, and that provides a
      safer means of enjoying nicotine. In addition, we tested a short, 8-item version
      of the measure which may be more easily incorporated into surveys. We tested the
      validity of the revised measure, both long and short versions, in terms of factor
      structure and associations of the expectancy factors with current e-cigarette
      use, e-cigarette use susceptibility, and e-cigarette use dependence. Participants
      were young adults (N=470; 65% women; mean age=20.9, SD=2.1). Results replicated
      the findings of the previous study as well as highlighted the importance of the
      added domain of positive "smoking" experience and the validity of the short
      scale. Furthermore, results showed that positive outcome expectancies are
      strongly associated with e-cigarette use dependence. The long and short versions
      of the revised youth e-cigarette outcome expectancies scale appear to be valid
      and useful for application not only among cigarette smokers and e-cigarette users
      but also among never smokers and never e-cigarette users.

PMID- 29195148
TI  - When do arrows start to compete? A developmental mouse-tracking study.
AB  - Recent work in adults has suggested that the strength of social and symbolic cues
      not presented at fixation (but allowing eye movements to the cue) may be
      determined less by their biological relevance and more by the distinctiveness of
      the shape of the cue. The present study examines whether these results extend to
      children, who may differ in their relative exposure to symbolic cues (arrows)
      compared to social cues. Children aged 3 to 11 were presented with congruent or
      incongruent pairs of cues (line drawings of gazing eyes, pointing hands, and
      arrows) and were asked to indicate the direction of the target cue (indicated at
      the start of the block) by moving the mouse towards the response box indicating
      its direction. Results show a similar advantage for arrows and pointing hands in
      young children as previously found in adults, suggesting that cue shape trumps
      biological relevance for cues away from fixation from an early age.

PMID- 29195149
TI  - Enhanced production of biosynthesized lycopene via heterogenous MVA pathway based
      on chromosomal multiple position integration strategy plus plasmid systems in
      Escherichia coli.
AB  - The multiple plasmid system, mostly relied, for heterogeneous gene expression,
      results in genetic instability and low mean productivity. To address this, an
      integration method was employed for investigating expression of heterogenous
      pathway in E. coli cells; where mevalonate upper pathway was found efficiently
      expressed. Subsequently, to improve lycopene production, chromosomal multiple
      position integration strategy was used to strengthen mevalonate upper pathway.
      Meanwhile, the plasmid system was employed for mevalonate lower pathway and
      lycopene pathway expression to finally generate the mutant D711 strain.
      Comparatively, highest level of 68.5 mg/L lycopene was produced by D711
      outperforming its maximum average productivity of 2.85 mg/L/h with over 2-folds
      enhancement. In addition, lycopene level was almost 224 mg/L after optimization
      of induction time, which was 3.3-fold higher than standard control condition.
      Finally, expression Performance Parameter was developed for scoring mutants and
      evaluating these two strategies, indicating chromosomal multiple position
      integration strategy as more efficient approach.

PMID- 29195150
TI  - Effect of different ammonia sources on aceticlastic and hydrogenotrophic
      methanogens.
AB  - Ammonium chloride (NH4Cl) was usually used as a model ammonia source to simulate
      ammonia inhibition during anaerobic digestion (AD) of nitrogen-rich feedstocks.
      However, ammonia in AD originates mainly from degradation of proteins, urea and
      nucleic acids, which is distinct from NH4Cl. Thus, in this study, the inhibitory
      effect of a "natural" ammonia source (urea) and NH4Cl, on four pure methanogenic
      strains (aceticlastic: Methanosarcina thermophila, Methanosarcina barkeri;
      hydrogenotrophic: Methanoculleus bourgensis, Methanoculleus thermophilus), was
      assessed under mesophilic (37  degrees C) and thermophilic (55  degrees C)
      conditions. The results showed that urea hydrolysis increased pH significantly to
      unsuitable levels for methanogenic growth, while NH4Cl had a negligible effect on
      pH. After adjusting initial pH to 7 and 8, urea was significantly stronger
      inhibitor with longer lag phases to methanogenesis compared to NH4Cl. Overall,
      urea seems to be more toxic on both aceticlastic and hydrogenotrophic methanogens
      compared to NH4Cl under the same total and free ammonia levels.

PMID- 29195151
TI  - Membrane fouling mechanism of biofilm-membrane bioreactor (BF-MBR): Pore blocking
      model and membrane cleaning.
AB  - Biofilm membrane bioreactor (BF-MBR) is considered as an important wastewater
      treatment technology that incorporates advantages of both biofilm and MBR
      process, as well as can alleviate membrane fouling, with respect to the
      conventional activated sludge MBR. But, to be efficient, it necessitates the
      establishment of proper methods for the assessment of membrane fouling. Four
      Hermia membrane blocking models were adopted to quantify and evaluate the
      membrane fouling of BF-MBR. The experiments were conducted with various
      operational conditions, including membrane types, agitation speeds and
      transmembrane pressure (TMP). Good agreement between cake formation model and
      experimental data was found, confirming the validity of the Hermia models for
      assessing the membrane fouling of BF-MBR and that cake layer deposits on
      membrane. Moreover, the influences of membrane types, agitation speeds and
      transmembrane pressure on the Hermia pore blocking coefficient of cake layer were
      investigated. In addition, the permeability recovery after membrane cleaning at
      various operational conditions was studied. This work confirms that, unlike
      conventional activated sludge MBR, BF-MBR possesses a low degree of membrane
      fouling and a higher membrane permeability recovery after cleaning.

PMID- 29195152
TI  - d-1,2,4-Butanetriol production from renewable biomass with optimization of
      synthetic pathway in engineered Escherichia coli.
AB  - Bio-based production of d-1,2,4-butanetriol (BT) from renewable substrates is
      increasingly attracting attention. Here, the BT biosynthetic pathway was
      constructed and optimized in Escherichia coli to produce BT from pure d-xylose or
      corncob hydrolysates. First, E. coli BL21(DE3) was identified as a more proper
      host for BT production through host screening. Then, BT pathway was
      systematically optimized with gene homolog screening strategy, mainly targeting
      three key steps from xylonic acid to BT catalyzed by d-xylonate dehydratase (XD),
      2-keto acid decarboxylase (KDC) and aldehyde reductase (ALR). After screening six
      ALRs, four KDCs and four XDs, AdhP from E. coli, KdcA from Lactococcus lactis and
      XylD from Caulobacter crescentus were identified more efficiently for BT
      production. The co-expression of these enzymes in recombinant strain BL21-14 led
      to BT production of 5.1 g/L under the optimized cultivation conditions. Finally,
      BT production from corncob hydrolysates was achieved with a titer of 3.4 g/L.

PMID- 29195153
TI  - Composition characterization and transformation mechanism of refractory dissolved
      organic matter from an ANAMMOX reactor fed with mature landfill leachate.
AB  - This study applied combined spectroscopy techniques to assess rDOM compositional
      characteristic and investigated its transformation mechanisms during the
      treatment of mature landfill leachate by ANAMMOX process. A novel rDOM metabolism
      mechanism was proposed in this study for the first time. A stable, high nitrogen
      removal rate of 5.95 kg N/m3/day and a rDOM conversion efficiency of 51% were
      achieved in ANAMMOX reactor (AR). In additionally, the initial rDOM removal was
      closely related to sludge adsorption, with the adsorption force mainly
      originating from electrostatic interaction and hydrophobicity. As the operating
      time increased, the removal mechanism of rDOM in the AR changed from adsorption
      to adsorption-biodegradation and finally stabilized. Furthermore,
      Anaerolineaceae, associated with the hydrophobic reaction, were the primary
      degraders for the rDOM and Candidatus Kuenenia dominated the nitrogen
      consumption. rDOM removal efficiency was suggested to be increased by a moderate
      enhancement of Anaerolineaceae content in the AR.

PMID- 29195154
TI  - Pyrolysis kinetics and thermodynamic parameters of castor (Ricinus communis)
      residue using thermogravimetric analysis.
AB  - Castor plant is a fast-growing, perennial shrub from Euphorbiaceae family. More
      than 50% of the residue is generated from its stems and leaves. The main aim of
      this work is to study the pyrolytic characteristics, kinetics and thermodynamic
      properties of castor residue. The TGA experiments were carried out from room
      temperature to 900  degrees C under an inert atmosphere at different heating
      rates of 5, 10, 15, 20, 30 and 40  degrees C/min. The kinetic analysis was
      carried using different models namely Kissinger, Flynn-Wall-Ozawa (FWO) and
      Kissinger-Akahira-Sunose (KAS). The average Ealpha calculated by FWO and KAS
      methods were 167.10 and 165.86 kJ/mole respectively. Gibbs free energy varied
      from 150.62-154.33 to 150.59-154.65 kJ/mol for FWO and KAS respectively. The HHV
      of castor residue was 14.43 MJ/kg, considered as potential feedstock for bio
      energy production. Kinetic and thermodynamic results will be useful input for the
      design of pyrolytic process using castor residue as feedstock.

PMID- 29195155
TI  - Complex effect of lignocellulosic biomass pretreatment with 1-butyl-3
      methylimidazolium chloride ionic liquid on various aspects of ethanol and fumaric
      acid production by immobilized cells within SSF.
AB  - The pretreatment of softwood and hardwood samples (spruce and hornbeam wood) with
      1-butyl-3-methylimidazolium chloride ([Bmim]Cl) was undertaken for further
      simultaneous enzymatic saccharification of renewable non-food lignocellulosic
      biomass and microbial fermentation of obtained sugars to ethanol and fumaric
      acid. A multienzyme cocktail based on cellulases and yeast or fungus cells
      producing ethanol and fumaric acid were the main objects of [Bmim]Cl influence
      studies. A complex effect of lignocellulosic biomass pretreatment with [Bmim]Cl
      on various aspects of the process (both action of cellulases and microbial
      conversion of hydrolysates to target products) was revealed. Positive effects of
      the pretreatment with [Bmim]Cl included decreasing the lignin content in the
      biomass, and increasing the effectiveness of enzymatic hydrolysis and microbial
      transformation of pretreated biomass. Immobilized cells of both yeasts and fungi
      possessed improved productive characteristics in the biotransformation of biomass
      pretreated with [Bmim]Cl to ethanol and fumaric acid.

PMID- 29195156
TI  - The transformation from anammox granules to deammonification granules in micro
      aerobic system by facilitating indigenous ammonia oxidizing bacteria.
AB  - Granular deammonification process is a good way to retain aerobic and anaerobic
      ammonia oxidizing bacteria (AOB and anammox bacteria) and exhaust flocculent
      nitrite oxidizing bacteria (NOB). In this study, to facilitate indigenous AOB
      growth on anammox granules, by stepwise reducing influent nitrite, anammox
      granules were effectively transformed into deammonification granules in a micro
      aerobic EGSB in 100 days. Total nitrogen removal efficiency of 90% and nitrogen
      removal rate of 2.3 g N/L/d were reached at stable deammonification stage. High
      influent FA and limited oxygen supply contributed suppression for Nitrospira-like
      NOB. In transition stages, Proteobacteria and Chloroflexi were always dominated.
      Anammox abundance decreased, while AOB abundance grew fast. Anammox bacteria and
      AOB were dominated by Brocadia fulgida and Nitrosomonas europaea, respectively.
      Denitrification activity and bacteria existed although without influent organic.
      The final AOB abundance was about 4.55-13.8 times more than anammox bacteria
      abundance, with almost equal potential activities.

PMID- 29195157
TI  - A meta-analysis of the association between vocalizations and expressive language
      in children with autism spectrum disorder.
AB  - BACKGROUND: Targeting the frequency or complexity of prelinguistic vocalizations
      might improve the language trajectory of children with autism spectrum disorder
      (ASD) who exhibit continued expressive language deficits. AIMS: This meta
      analysis evaluates the strength of the association between various measures of
      vocalizations and expressive language in young children with ASD and five
      putative moderators of that association to inform prelinguistic intervention
      development: consonant-centricity, communicativeness, concurrent versus
      longitudinal research design, risk for correlated measurement error, and
      publication status. METHODS AND PROCEDURES: We systematically searched databases
      and other sources for correlations between vocalizations and expressive language
      in children with ASD less than 9 years old. Using robust variance estimation, we
      calculated the weighted mean effect size and conducted moderator analyses.
      OUTCOMES AND RESULTS: Nine studies (19 reports), which included 362 participants
      and 109 unique effect sizes, met inclusion criteria. The weighted mean effect
      size between vocalizations and expressive language was significant (r=0.50, 95%
      CI [0.23, 0.76]). As predicted, concurrent correlations were significantly
      stronger than longitudinal correlations. Other moderator effects were not
      detected. CONCLUSIONS AND IMPLICATIONS: Young children with ASD demonstrate a
      strong association between vocalizations and expressive language skills. Future
      experimental studies should investigate causal relations to guide intervention
      development.

PMID- 29195158
TI  - Corticospinal excitability during motor imagery is reduced in young adults with
      developmental coordination disorder.
AB  - While a compelling body of behavioral research suggests that individuals with
      developmental coordination disorder (DCD) experience difficulties engaging motor
      imagery (MI), very little is known about the neural correlates of this deficit.
      Since corticospinal excitability is a predictor of MI proficiency in healthy
      adults, we reasoned that decreased MI efficiency in DCD may be paralleled by
      atypical primary motor cortex (PMC) activity. Participants were 29 young adults
      aged 18- 36 years: 8 with DCD (DCD) and 21 controls. Six participants with DCD
      and 15 controls showed behavioral profiles consistent with the use of a MI
      strategy (MI users) while performing a novel adaptation of the classic hand
      laterality task (HLT). Single-pulse transcranial magnetic stimulation (TMS) was
      administered to the hand node of the left PMC (hPMC) at 50ms, 400ms or 650ms post
      stimulus presentation during the HLT. Motor-evoked potentials (MEPs) were
      recorded from the right first dorsal interosseous (FDI) via electromyography. As
      predicted, MI users with DCD were significantly less efficient than MI using
      controls, shown by poorer performance on the HLT. Importantly, unlike healthy
      controls, no evidence of enhanced hPMC activity during MI was detected in our DCD
      group. Our data are consistent with the view that inefficient MI in DCD may be
      subserved by decreased hPMC activity. These findings are an important step
      towards clarifying the neuro-cognitive correlates of poor MI ability and motor
      skill in individuals with DCD.

PMID- 29195159
TI  - Inactivation kinetics and efficiencies of UV-LEDs against Pseudomonas aeruginosa,
      Legionella pneumophila, and surrogate microorganisms.
AB  - To demonstrate the effectiveness of UV light-emitting diodes (UV-LEDs) to
      disinfect water, UV-LEDs at peak emission wavelengths of 265, 280, and 300 nm
      were adopted to inactivate pathogenic species, including Pseudomonas aeruginosa
      and Legionella pneumophila, and surrogate species, including Escherichia coli,
      Bacillus subtilis spores, and bacteriophage Qbeta in water, compared to
      conventional low-pressure UV lamp emitting at 254 nm. The inactivation profiles
      of each species showed either a linear or sigmoidal survival curve, which both
      fit well with the Geeraerd's model. Based on the inactivation rate constant, the
      265-nm UV-LED showed most effective fluence, except for with E. coli which showed
      similar inactivation rates at 265 and 254 nm. Electrical energy consumption
      required for 3-log10 inactivation (EE,3) was lowest for the 280-nm UV-LED for all
      microbial species tested. Taken together, the findings of this study determined
      the inactivation profiles and kinetics of both pathogenic bacteria and surrogate
      species under UV-LED exposure at different wavelengths. We also demonstrated that
      not only inactivation rate constants, but also energy efficiency should be
      considered when selecting an emission wavelength for UV-LEDs.

PMID- 29195160
TI  - Modulation of the anticonvulsant effect of swim stress by agmatine.
AB  - Agmatine is an endogenous l-arginine metabolite with neuroprotective effects in
      the stress-response system. It exerts anticonvulsant effects against several
      seizure paradigms. Swim stress induces an anticonvulsant effect by activation of
      endogenous antiseizure mechanisms. In this study, we investigated the interaction
      of agmatine with the anticonvulsant effect of swim stress in mice on
      pentylenetetrazole (PTZ)-induced seizure threshold. Then we studied the
      involvement of nitric oxide (NO) pathway and endogenous opioid system in that
      interaction. Swim stress induced an anticonvulsant effect on PTZ seizures which
      was opioid-independent in shorter than 1-min swim durations and opioid-dependent
      with longer swims, as it was completely reversed by pretreatment with naltrexone
      (NTX) (10mg/kg), an opioid receptor antagonist. Agmatine significantly enhanced
      the anticonvulsant effect of opioid-independent shorter swim stress, in which a
      combination of subthreshold swim stress duration (45s) and subeffective dose of
      agmatine (1mg/kg) revealed a significantly higher seizure threshold compared with
      either one. This effect was significantly reversed by NO synthase inhibitor NG
      nitro-l-arginine (L-NAME (Nomega-Nitro-L-arginine methyl ester), 5mg/kg),
      suggesting an NO-dependent mechanism, and was unaffected by NTX (10mg/kg),
      proving little role for endogenous opioids in the interaction. Our data suggest
      that pretreatment of animals with agmatine acts additively with short swim stress
      to exert anticonvulsant responses, possibly by mediating NO pathway.

PMID- 29195161
TI  - Prenatal and pubertal testosterone affect brain lateralization.
AB  - After decades of research, the influence of prenatal testosterone on brain
      lateralization is still elusive, whereas the influence of pubertal testosterone
      on functional brain lateralization has not been investigated, although there is
      increasing evidence that testosterone affects the brain in puberty. We performed
      a longitudinal study, investigating the relationship between prenatal
      testosterone concentrations in amniotic fluid, pubertal testosterone
      concentrations in saliva, and brain lateralization (measured with functional
      Transcranial Doppler ultrasonography (fTCD)) of the Mental Rotation, Chimeric
      Faces and Word Generation tasks. Thirty boys and 30 girls participated in this
      study at the age of 15 years. For boys, we found a significant interaction effect
      between prenatal and pubertal testosterone on lateralization of Mental Rotation
      and Chimeric Faces. In the boys with low prenatal testosterone levels, pubertal
      testosterone was positively related to the strength of lateralization in the
      right hemisphere, while in the boys with high prenatal testosterone levels,
      pubertal testosterone was negatively related to the strength of lateralization.
      For Word Generation, pubertal testosterone was negatively related to the strength
      of lateralization in the left hemisphere in boys. For girls, we did not find any
      significant effects, possibly because their pubertal testosterone levels were in
      many cases below quantification limit. To conclude, prenatal and pubertal
      testosterone affect lateralization in a task-specific way. Our findings cannot be
      explained by simple models of prenatal testosterone affecting brain
      lateralization in a similar way for all tasks. We discuss alternative models
      involving age dependent effects of testosterone, with a role for androgen
      receptor distribution and efficiency.

PMID- 29195162
TI  - Effects of adolescent social stress and antidepressant treatment on cognitive
      inflexibility and Bdnf epigenetic modifications in the mPFC of adult mice.
AB  - Adolescent social stress (ASS) can increase susceptibility to depression in
      adulthood. However, the underlying psychological and neural mechanisms remain
      unclear. Cortically mediated cognitive dysfunctions are increasingly recognized
      as an independent and important risk factor of depression. Using social defeat
      stress, a classical animal model of depression, our previous studies found that
      mice subjected to this form of stress during early adolescence displayed
      cognitive inflexibility (CI) in adulthood. This change was accompanied by a down
      regulation of Bdnf gene expression in the medial prefrontal cortex (mPFC); this
      gene encodes a key molecule involved in depression and antidepressant action. In
      the present paper, we identified epigenetic modification of Bdnf as a possible
      mechanism underlying the behavioral and molecular changes. ASS induced a set of
      depressive phenotypes, including increased social avoidance and CI, as well as
      reduced levels of total Bdnf and isoform IV but not isoform I or VI transcripts
      in the mPFC. In parallel with changes in Bdnf gene expression, previously
      stressed adult mice showed increased levels of dimethylation of histone H3 at
      lysine K9 (H3K9me2) immediately downstream of the Bdnf IV promoter. On the other
      hand, no differences were found in trimethylation of histone H3 at lysine K4
      (H3K4me3) or in acetylation of histone H3 at lysine K9 (H3K9ac) or at K4 (H3K4ac)
      in the Bdnf IV promoter. Likewise, no alterations were found in DNA methylation
      of the Bdnf IV promoter. Additionally, treatment with the chronic antidepressant
      tranylcypromine reversed Bdnf epigenetic changes and related gene transcription
      while also reversing CI, but not social avoidance, in previously stressed adult
      mice. These results suggest that epigenetic changes to the Bdnf gene in the mPFC
      after adolescent social adversity may be involved in the regulation of cognitive
      dysfunction in depression and antidepressant action in adulthood.

PMID- 29195163
TI  - Environmental impacts of heavy metals, rare earth elements and natural
      radionuclides in marine sediment from Ras Tanura, Saudi Arabia along the Arabian
      Gulf.
AB  - Ras Tanura city is one of the most important cities in Saudi Arabia because of
      the presence of the largest and oldest oil refinery in the Middle East which was
      began operations in September 1945. Also its contains gas plant and two ports.
      The concentration of natural radionuclides, heavy metals and rare earth elements
      were measured in marine sediment samples collected from Ras Tanura. The specific
      activities of 238U, 226Ra, 232Th, 40K and 137Cs (Bq/kg) were measured using A
      hyper-pure Germanium detector (HPGe), and ranged from (20.4 +/- 4.0-55.1 +/-
      9.9), (6.71 +/- 0.7-46.1 +/- 4.5), (3.51 +/- 0.5-18.2 +/- 1.5), (105 +/- 4.4-492
      +/- 13) and from (0.33 +/- 0.04-2.10 +/- 0.4) for 238U, 226Ra, 232Th, 40K and
      137Cs respectively. Heavy metals and rare earth elements were measured using ICPE
      9820 Plasma Atomic Emission Spectrometer. Also the frequency distributions for
      all radioactive variables in sediment samples were analyzed. Finally the
      radiological hazards due to natural radionuclides in marine sediment were
      calculated to the public and it's diagramed by Surfer program in maps. Comparing
      with the international recommended values, its values found to be within the
      international level.

PMID- 29195165
TI  - Psychometric evaluation of the Temporal Experience of Pleasure Scale (TEPS) in a
      German sample.
AB  - Anhedonia, or the inability to experience pleasure, is commonly observed in
      schizophrenia. It has been suggested that patients with schizophrenia are unable
      to predict future pleasurable events, but show intact experience of in-the-moment
      pleasure. Therefore, the Temporal Experience of Pleasure Scale (TEPS), a self
      report measure allowing the assessment of anticipatory and consummatory pleasure,
      has been developed. To validate the German version of the TEPS, we recruited 59
      healthy control participants and 51 patients with schizophrenia or
      schizoaffective disorder who completed the TEPS as well as a battery of
      psychometric tests to assess psychopathology, in particular self-rated anhedonia
      and clinician-rated apathy as well as overall measures of negative symptoms. We
      found acceptable to good internal consistency and a factor structure comparable
      to the original version. Scores of the TEPS were related to measures of anhedonia
      and apathy, but not with other measures of psychopathology. The present results
      suggest that the German version of the TEPS shows adequate reliability and
      validity to assess the construct of anhedonia. However, differential aspects of
      anticipatory and consummatory pleasure should be further investigated in clinical
      samples.

PMID- 29195164
TI  - Elderly migrants in outpatient and inpatient care services in Baden
      Wurttemberg/Germany.
AB  - OBJECTIVE: Given the expected underrepresentation of elderly migrant populations
      in healthcare utilization we examined their proportion in nursing homes and care
      services for the elderly. We expected that cultural aspects were rarely addressed
      in the services' concepts. METHODS: A questionnaire was administered to all care
      providers; 66.3% of 2724 in- and outpatient services in Baden-Wurttemberg,
      Germany participated. RESULTS: 78% of the services provided healthcare to
      migrants, who accounted for 14.1% of the clientele. This proportion was higher in
      urban (e.g. Heilbronn: 16.1%) than in rural areas (e.g. Lake Constance: 7.7%) and
      was significantly (r = 0.545, p < .05) correlated with the proportion of migrants
      in the general population. 39.1% of the migrants came from Russia, Poland and
      Turkey. Migrants from Turkey preferred outpatients' rather than inpatients'
      services. While 87.4% of services employed migrants, only 20% of services
      provided measures to increase intercultural competency to their employees.
      CONCLUSIONS: Migrants utilize inpatient and outpatient services regularly as
      their proportion was closely associated to that of the general population.
      Although their number will likely increase in the near future, the vast majority
      of nursing facilities did not provide specialized measures to better meet the
      demands of residents with a migration background.

PMID- 29195166
TI  - Cognitive abilities and theory of mind in explaining communicative-pragmatic
      disorders in patients with schizophrenia.
AB  - Patients with schizophrenia usually show an impairment in their communicative
      pragmatic performance; they also have difficulties in cognitive functioning and
      Theory of Mind (ToM). In the literature it has been proposed that ToM and
      cognitive deficits have a role in explaining the communicative-pragmatic
      difficulties of patients with schizophrenia. However, the exact interplay of
      these functions is still not completely clear. The present research investigates
      the relationship between communicative-pragmatic, ToM and cognitive impairments
      (i.e. general intelligence, selective attention, speed processing and EF -working
      memory, inhibition and flexibility-) in a sample of 26 individuals with
      schizophrenia and matched controls. The linguistic and extralinguistic scales of
      the Assessment Battery of Communication (ABaCo), and a series of ToM and
      cognitive tasks were administered to patients and healthy controls. The results
      showed that individuals with schizophrenia performed less well than controls in
      all the tasks investigated. However, a hierarchical regression analysis showed
      that only ToM, and not cognitive functions, seems to be a predictive variable of
      patients' performance. Finally, a Fisher's exact test showed that there was not a
      stable significant relationship between ToM or EF and pragmatic impairment.

PMID- 29195167
TI  - Effects of short- and long-term aripiprazole treatment on Group I mGluRs in the
      nucleus accumbens: Comparison with haloperidol.
AB  - The D2 receptor partial agonist, aripiprazole, has shown increased therapeutic
      efficacy for schizophrenia, autism and Tourette's syndrome compared to
      traditional antipsychotics such as the D2 receptor antagonist, haloperidol.
      Recent evidence suggests this superior profile may be associated with downstream
      effects on glutamatergic synapses. Group 1 metabotropic glutamate receptors
      (mGluRs) and their endogenous modulators, Norbin and Homer1, are regulated by D2
      receptor activity, particularly within the nucleus accumbens (NAc), a target
      region of aripiprazole and haloperidol. This study sought to evaluate the effects
      of aripiprazole on Group 1 mGluRs, Norbin and Homer1 in the NAc, in comparison to
      haloperidol. Sprague-Dawley rats were orally administered daily doses of
      aripiprazole (2.25mg/kg), haloperidol (0.3mg/kg) or vehicle for 1 or 10-weeks.
      Immunoblot analyses revealed Group 1 mGluR protein levels were not altered
      following 1-week and 10-week aripiprazole or haloperidol treatment, compared to
      vehicle treated rodents. However, 1-week aripiprazole and haloperidol treatment
      significantly elevated Homer1a and Norbin protein expression, respectively. After
      10 weeks of treatment, aripiprazole, but not haloperidol, significantly increased
      Norbin expression. These findings indicate the antipsychotics, aripiprazole and
      haloperidol, exert differential temporal effects on Norbin and Homer1 expression
      that may have consequences on synaptic glutamatergic transmission underlying
      their therapeutic profile.

PMID- 29195168
TI  - Stochastic optimal generation bid to electricity markets with emissions risk
      constraints.
AB  - There are many factors that influence the day-ahead market bidding strategies of
      a generation company (GenCo) within the framework of the current energy market.
      Environmental policy issues are giving rise to emission limitation that are
      becoming more and more important for fossil-fueled power plants, and these must
      be considered in their management. This work investigates the influence of the
      emissions reduction plan and the incorporation of the medium-term derivative
      commitments in the optimal generation bidding strategy for the day-ahead
      electricity market. Two different technologies have been considered: the high
      emission technology of thermal coal units and the low-emission technology of
      combined cycle gas turbine units. The Iberian Electricity Market (MIBEL) and the
      Spanish National Emissions Reduction Plan (NERP) defines the environmental
      framework for dealing with the day-ahead market bidding strategies. To address
      emission limitations, we have extended some of the standard risk management
      methodologies developed for financial markets, such as Value-at-Risk (VaR) and
      Conditional Value-at-Risk (CVaR), thus leading to the new concept of Conditional
      Emission at Risk (CEaR). This study offers electricity generation utilities a
      mathematical model for determining the unit's optimal generation bid to the
      wholesale electricity market such that it maximizes the long-term profits of the
      utility while allowing it to abide by the Iberian Electricity Market rules as
      well as the environmental restrictions set by the Spanish National Emissions
      Reduction Plan. We analyze the economic implications for a GenCo that includes
      the environmental restrictions of this National Plan as well as the NERP's
      effects on the expected profits and the optimal generation bid.

PMID- 29195169
TI  - Modelling interactive effects of multiple disturbances on a coastal lake
      ecosystem: Implications for management.
AB  - Coastal lakes, also known as temporarily open/closed estuaries or intermittently
      closed and open lakes and lagoons, are common worldwide, are typically sites of
      high biodiversity and often contain abundant macrophyte populations.
      Anthropogenic stressors such as increased nutrient and sediment loading have
      adverse effects on submerged macrophytes, and when closed, the lack of tidal
      flushing makes coastal lakes highly susceptible to eutrophication. Lake openings
      to the sea may occur naturally, but many coastal lakes are also opened
      artificially, often to reduce inundation of surrounding land. Here we used a
      coupled hydrodynamic-ecological model (DYRESM-CAEDYM), modified to include
      dynamic feedback between submerged macrophyte biomass and sediment resuspension,
      to explore the interactive effects of multiple disturbances (openings,
      eutrophication and climate change) on the dynamics of primary producers in a
      coastal lake (Waituna Lagoon) in South Island, New Zealand. Our results indicate
      that with exposure to high external nutrient loads, the frequent disturbances
      caused by artificial openings prevent sustained dominance by algae (algal biomass
      averaged 192 g C m-2 with artificial openings compared to 453 g C m-2 with no
      openings). However, under current nutrient loading, climate change is likely to
      enhance the effects of eutrophication on the system (algal biomass averaged 227 g
      C m-2 with climate change compared with 192 g C m-2 for current climate). The
      model provides a decision-support tool to guide lake management in setting limits
      for nutrient loads and managing the opening regime, in order to prevent
      eutrophication and the potential collapse of the macrophyte community.

PMID- 29195170
TI  - Risk of maltreatment for siblings: Factors associated with similar and different
      childhood experiences in a dyadic sample of adult siblings.
AB  - Siblings share the same environment and thus potentially a substantial number of
      risk factors for child maltreatment. Furthermore, the number of siblings and the
      sibling constellation itself might pose a risk for child maltreatment. Little is
      known about the likelihood that more than one child in a family is maltreated and
      which factors increase the risk. This study sought to investigate similarities
      and differences in maltreatment in siblings and risk factors associated with the
      maltreatment of more than one child from the same family. Data on maltreatment
      during childhood and adolescence, family background, and sibling constellation
      were collected from 870 pairs of siblings. In the dyadic analyses, siblings
      reported similar maltreatment experiences, especially when any type of
      maltreatment was considered. Parents' mental health problems were significant
      predictors for maltreatment of at least one sibling. Father's mental health
      problems were predictive of maltreatment of both or only the younger sibling,
      mother's mental health problems of both or only the older sibling. Closeness in
      age and same gender of siblings did not emerge as a consistent predictor. The
      increasing number of siblings was a risk factor for any type of maltreatment of
      both siblings. The results highlight the need for preventive measures for
      families with a large number of children and with parents with mental health
      problems as well as a repeated risk assessment of all siblings in a family when
      one sibling was maltreated.

PMID- 29195172
TI  - Exposure to school violence at school and mental health of victimized
      adolescents: The mediation role of social support.
AB  - The purpose of the current study is to examine the mediation role of social
      support in the relationship between exposure to violence at school and mental
      health among adolescents within the framework of two structured models via
      structural equation model (SEM). The participants consist of a total of 1420 9th,
      10th, and 11th grades high school students (54.5% girls and 45.5% boys). The
      students' ages ranged from 14 to 18 years with a mean of 16.11 (SD=0.91) for
      total sample. 38 percent of the participants are in the 9th grade, 34.1 percent
      are in the 10th grade, and 28 percent are in the 11th grade. Findings from both
      models indicated that social support mediated the relationships between exposure
      to violence and mental health among adolescents. Additionally, both models showed
      that the associations between exposure to violence, social support and mental
      health varied by gender. Contributions and implications of the current findings
      are discussed in detail.

PMID- 29195171
TI  - Commercially sexually exploited youths' health care experiences, barriers, and
      recommendations: A qualitative analysis.
AB  - The current study sought to understand commercially sexually exploited (CSE)
      youths' health care experiences, barriers to care, and recommendations for
      improving health care services. We conducted focus groups (N=5) with 18 CSE youth
      from February 2015 through May 2016 at two group homes serving CSE youth in
      Southern California. We performed thematic content analysis to identify emergent
      themes about CSE youths' perspectives on health care. Youth described
      facilitators to care, including availability of services such as screening for
      sexually transmitted infections, knowledge about sexual health, and a strong
      motivation to stay healthy. Barriers included feeling judged, concerns about
      confidentiality, fear, perceived low quality of services, and self-reliance.
      Overall, youth emphasized self-reliance and "street smarts" for survival and de
      emphasized "victimhood," which shaped their interactions with health care, and
      recommended that health providers develop increased understanding of CSE youth.
      Our findings suggest that providers and community agencies can play an essential
      role in raising awareness of the needs of CSE youth and meet their health needs
      through creating a non-judgmental environment in health care settings that
      validates the experiences of these youth.

PMID- 29195173
TI  - Developmental trajectories and longitudinal mediation effects of self-esteem,
      peer attachment, child maltreatment and depression on early adolescents.
AB  - OBJECTIVES: The purpose of this study is to identify the developmental
      trajectories of peer attachment, self-esteem, depression, and child maltreatment,
      and to understand the longitudinal mediation effects that peer attachment and
      self-esteem have on the influence of perceived abuse on early adolescent
      depression. METHODS: This study uses Year 1 to Year 5 data of the 4th grader
      panel of the Korea Youth Panel Survey (KYPS) and utilizes a multivariate latent
      growth model to analyze the main variables in the applicable data between 5th
      (i.e., Year 2) and 8th (i.e., Year 5) grades. RESULTS: The results indicate that
      from the 5th to the 8th grade, the degree of abuse and depression increases while
      self-esteem gradually decreases with slowly lowering peer attachment. A
      significant distribution of the initial values and the rate of change were
      present for all main variables of the study, confirming individual differences in
      time wise changes. Further, more exposure to abuse correlated with a decrease in
      self-esteem, while an increase in self-esteem greatly reduced depression. The
      initial value of self-esteem showed a partial mediation effect, whereas the rate
      of change indicated a full mediation effect with a significant longitudinal
      mediation effect. More experience of abuse during early adolescence indicated a
      lower degree of peer attachment, and a higher peer attachment was related to
      decreased depression. A significant partial mediation effect was present for both
      the initial value and the rate of change of peer attachment, and a longitudinal
      mediation effect was present. PRACTICE IMPLICATIONS: This study confirmed that
      self-esteem in early adolescents is an important protective factor that can
      greatly reduce the degree of depression, and suggests continuous interventions
      conducted to increase self-esteem in adolescence. Furthermore, by determining
      that peer attachment decreases the degree of depression in children at risk, the
      study emphasizes the healing aspect of adolescent peer attachment.

PMID- 29195174
TI  - Abusive fracture incidence over three decades at a level 1 pediatric trauma
      center.
AB  - Few studies have examined the incidence of abusive fractures in children. Only
      one study to date, from a single pediatric trauma center,has reported on the
      incidence of abusive fractures over time. That study showed a decrease in abusive
      fractures over a 24-year period. Our objective for this current study was to
      compare these published data with recent data from this same trauma center,
      allowing for a detailed comparison of the incidence of abusive fractures over a
      30-year period. We included children <36months of age who presented to the
      emergency department of a level 1 pediatric trauma center (2007-2010) with>=1
      fracture. Six experts from 3 different fields rated each case on the likelihood
      the fracture(s) was caused by abuse using an established 7- point scale, and a
      consensus rating was agreed upon for each case. The incidence of abusive
      fractures was calculated per 10,000 children <36months of age living in the
      geographic region and per 10,000 ED visits and was compared to previously
      published data for three prior time periods (1979-1983, 1991-1994, and 1999-2002)
      at the same pediatric trauma center. From 2007-2010, 551 children were
      identified, including 31 children who were rated as abused. The incidence of a
      child presenting with an abusive fracture in the county per year was 2.7/10,000
      children <36months of age. The previous three time periods showed a countywide
      incidence of 3.2/10,000 (1979-1983), 1.7/10,000 (1991-1994), and 2.0/10,000 (1999
      2002) (p for trend 0.34). The incidence per ED visit was 2.5/10,000 in the recent
      time period compared to 6.0/10,000 (1979-1983), 3.4/10,000 (1991-1994), and
      2.5/10,000 (1999-2002) (p for trend <0.001). In this single institution review of
      fractures in children <36months of age, the incidence of abusive fractures has
      remained relatively constant over a 30-year period.

PMID- 29195175
TI  - Distribution of ARGs and MGEs among glacial soil, permafrost, and sediment using
      metagenomic analysis.
AB  - Antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) can be
      identified with metagenomic analyses comparing relatively pristine and human
      impacted environments. We collected samples from 3 different environments:
      glacial soil little affected by anthropogenic activity, deep permafrost dated to
      5821 BP (before human antibiotics), and sediment from the Pearl River.
      Sulfonamides, tetracyclines, and fluoroquinolones were common in the sediment
      samples. Sulfonamides and tetracycline were not found in permafrost; tetracycline
      was also not found in glacial soil. ARGs from the sediment were more abundant and
      diverse than those from glacial soil and permafrost. More types of resistance
      mechanisms were also present in the sediment. The diversity of MGEs was
      significantly correlated with the abundance and diversity of ARGs. The result
      will help future workers to better understand the distribution of ARGs among
      environments more or less impacted by anthropogenic activities.

PMID- 29195176
TI  - Using the Asian clam as an indicator of microplastic pollution in freshwater
      ecosystems.
AB  - Bioindicators play an important role in understanding pollution levels,
      bioavailability and the ecological risks of contaminants. Several bioindicators
      have been suggested for understanding microplastic in the marine environment. A
      bioindicator for microplastics in the freshwater environment does not exist. In
      our previous studies, we found a high frequency of microplastic pollution in the
      Asian clam (Corbicula fluminea) in Taihu Lake, China. In the present study, we
      conducted a large-scale survey of microplastic pollution in Asian clams, water
      and sediment from 21 sites in the Middle-Lower Yangtze River Basin from August to
      October of 2016. The Asian clam was available in all sites, which included
      diverse freshwater systems such as lakes, rivers and estuaries. Microplastics
      were found at concentrations ranging from 0.3-4.9 items/g (or 0.4-5.0
      items/individual) in clams, 0.5-3.1 items/L in water and 15-160 items/kg in
      sediment. Microfibers were the most dominant types of microplastics found,
      accounting for 60-100% in clams across all sampling sites. The size of
      microplastics ranged from 0.021-4.83 mm, and microplastics in the range of 0.25-1
      mm were dominant. The abundance, size distribution and color patterns of
      microplastics in clams more closely resembled those in sediment than in water.
      Because microplastic pollution in the Asian clam reflected the variability of
      microplastic pollution in the freshwater environments, we demonstrated the Asian
      clam as an bioindicator of microplastic pollution in freshwater systems,
      particularly for sediments.

PMID- 29195177
TI  - Mean and turbulent mass flux measurements in an idealised street network.
AB  - Pollutant mass fluxes are rarely measured in the laboratory, especially their
      turbulent component. They play a major role in the dispersion of gases in urban
      areas and modern mathematical models often attempt some sort of parametrisation.
      An experimental technique to measure mean and turbulent fluxes in an idealised
      urban array was developed and applied to improve our understanding of how the
      fluxes are distributed in a dense street canyon network. As expected, horizontal
      advective scalar fluxes were found to be dominant compared with the turbulent
      components. This is an important result because it reduces the complexity in
      developing parametrisations for street network models. On the other hand,
      vertical mean and turbulent fluxes appear to be approximately of the same order
      of magnitude. Building height variability does not appear to affect the exchange
      process significantly, while the presence of isolated taller buildings upwind of
      the area of interest does. One of the most interesting results, again, is the
      fact that even very simple and regular geometries lead to complex advective
      patterns at intersections: parametrisations derived from measurements in simpler
      geometries are unlikely to capture the full complexity of a real urban area.

PMID- 29195178
TI  - Short-term intraindividual variability of the posterior dominant alpha frequency
      in the electroencephalogram.

PMID- 29195179
TI  - Fe-polyaniline composite nanofiber catalyst for chemoselective hydrolysis of
      oxime.
AB  - A facile chemoselective one-pot strategy for the deprotection of oxime has been
      developed using Fe0-polyaniline composite nanofiber (Fe0-PANI), as a catalyst.
      Nano material based Fe0-PANI catalyst has been synthesized via in-situ
      polymerization of ANI monomer and followed by reductive deposition of Fe0 onto
      PANI matrix. The catalyst was characterized by FE-SEM, HR-TEM, BET, XRD, ATR
      FTIR, XPS and VSM techniques. The scope of the transformation was studied for
      aryl, alkyl and heteroarylketoxime with excellent chemoselectivity (>99%).
      Mechanistic investigations suggested the involvement of a cationic intermediate
      with Fe3+ active catalytic species. Substituent effect showed a linear free
      energy relationship. The activation energy (Ea) was calculated to be 17.46 kJ mol
      1 for acetophenone oxime to acetophenone conversion. The recyclability of the
      catalyst demonstrated up to 10 cycles without any significant loss of efficiency.
      Based on the preliminary experiments a plausible mechanism has been proposed
      involving a carbocationic intermediate.

PMID- 29195180
TI  - Mechanistic insights into the role of glycosaminoglycans in delivery of polymeric
      nucleic acid nanoparticles by molecular dynamics simulations.
AB  - Delivery of polynucleotide-based therapeutics into target cells involves
      interactions with glycosaminoglycan chains that are located on cell membrane
      milieu. Mechanisms governing glycosaminoglycan-mediated changes in the
      nanoparticulate structures of polymer-polynucleotide complexes are unknown, and
      cannot be fully elucidated without atomistic level details of molecular
      interactions. We selected a representative nanoparticulate system consisting of a
      short interfering RNA (siRNA)-polyethylenimine complex, and performed all-atom
      molecular dynamics simulations with the prototypical glycosaminoglycan heparin.
      We monitored the binding between the complex constituents and the heparin, and
      identified key features contributing to the response of the siRNA nanoparticles
      to heparin. We observed three main metastable states that the siRNA nanoparticles
      might visit in the presence of heparin, which can be translated into different
      functional outcomes. By correlating our data with the widely different and
      seemingly contradictory roles previously assigned to glycosaminoglycans, this
      study provides unique insights into the discrepancies in the experimental
      literature concerning the role of glycosaminoglycans in the polymeric
      nanoparticle delivery.

PMID- 29195181
TI  - One-pot synthesis of pH-responsive charge-switchable PEGylated nanoscale
      coordination polymers for improved cancer therapy.
AB  - Nanoscale coordination polymers (NCPs) are promising nanomedicine platforms
      featured with biodegradability and versatile functionalities. However, multi-step
      post-synthesis surface modification is usually required to functionalize as-made
      NCPs before their biomedical applications. Moreover, efforts are still required
      to design therapeutic NCPs responsive to the unique tumor microenvironment to
      achieve more specific and effective therapy. Herein, we uncover a simple yet
      general strategy to synthesize a series of polyethylene glycol (PEG) modified
      NCPs via a one-step method by adding poly-histidine-PEG co-polymer into the
      mixture of metal ions and organic ligands during NCPs formation. With NCPs
      consisting Ca2+/dicarboxylic cisplatin (IV) prodrug as the example, we show that
      such Ca/Pt(IV)@pHis-PEG NCPs are highly sensitive to pH changes. With slightly
      negative charges and compact structure under pH 7.4 during blood circulation,
      those NCPs exhibit efficient passive accumulation in the tumor, in which the
      reduced pH (c.a. 6.5) would trigger charge conversion and size expansion to
      enhance their tumor retention and cell internationalization. After cellular
      uptake, NCPs within cell endo-/lysosomes with further reduced pH would then lead
      to decomposition of those NCPs and thus drug release. Chemotherapy with
      Ca/Pt(IV)@pHis-PEG NCPs in our animal tumor model demonstrates great efficacy
      under low drug doses, and is found to be particularly effective towards solid
      tumors with reduced pH.

PMID- 29195182
TI  - A mitochondrial-targeting near-infrared fluorescent probe for bioimaging and
      evaluating endogenous superoxide anion changes during ischemia/reperfusion
      injury.
AB  - The outburst of superoxide anion (O2-) in mitochondrial during
      ischemia/reperfusion (I/R) process will cause a series of oxidative damage
      including polarity loss of mitochondrial membrane potential, overload of
      secondary cellular calcium, and cascade apoptosis. To monitor the O2- level
      fluctuations as well as to evaluate the relationship between O2- concentration
      and the degree of cell apoptosis during I/R process, we propose a ratiometric
      near-infrared mitochondrial targeting fluorescent probe Mito-Cy-Tfs for the
      detection of level changes of O2- in cells and in vivo. The probe Mito-Cy-Tfs is
      composed of three moieties: near-infrared heptamethine cyanine as fluorescence
      signal transducer, trifluoromethanesulfonamide as fluorescence modulator, and
      lipophilic triphenylphosphonium cation as mitochondrial guider. The probe can
      well locate in mitochondria and respond the concentration changes of endogenous
      O2- selectively and sensitively. The probe has been successfully utilized to
      image the endogenous O2- fluctuations in four kinds of cell I/R models (glucose
      deprivation/reperfusion, serum deprivation/reperfusion, oxygen
      deprivation/reperfusion and glucose-serum-oxygen deprivation/reperfusion). The
      probe also exhibits deep tissue penetration for real-time imaging of O2
      concentration in liver of I/R mice model. We confirm that the adoption of
      ischemic preconditioning (IPC) and postconditioning (IPTC) can protect liver from
      I/R injury. The probe can be employed to accurately indicate and evaluate the
      mutual relationship between the levels of O2- and the degrees of organ damage
      during I/R, IPC and IPTC processes. The above applications make our new probe a
      potential candidate for the clinical surgery assessment.

PMID- 29195183
TI  - Impacts of exposure to black carbon, elemental carbon, and ultrafine particles
      from indoor and outdoor sources on blood pressure in adults: A review of
      epidemiological evidence.
AB  - INTRODUCTION: Ambient particulate air pollution is known to have detrimental
      effects on cardiovascular health but less is known about the specific effects of
      black carbon or elemental carbon (BC/EC) and ultrafine particles (UFP). METHODS:
      We present a narrative review of the epidemiological evidence related to the
      impact of exposure to BC/EC and UFP on blood pressure in adults. We searched
      PubMed and EMBASE in September 2017, using a predefined search strategy.
      Abstracts were screened using predefined inclusion criteria. Data collection was
      completed using a standard data extraction form. We focused on main effect
      estimates for associations between short (<=7 days) and long-term exposures to
      BC/EC and UFP and systolic (SBP) and diastolic blood pressure (DBP). Effect
      estimates were rescaled to enable direct comparisons between studies. RESULTS:
      Thirty publications were included in the review: 19 studies examined outdoor
      exposure to BC/EC, 11 examined outdoor UFP, three studies examined indoor BC and
      one study examined indoor UFP. In general, existing evidence supports a positive
      association between BC/EC and blood pressure. Evidence for outdoor UFP exposures
      were less clear as effect estimates were small in magnitude and confidence
      intervals often included the null. CONCLUSIONS: Existing evidence supports a
      positive association between BC/EC and blood pressure in adults, whereas UFPs do
      not appear to have a meaningful impact on blood pressure.

PMID- 29195184
TI  - Bioaccumulation of persistent and emerging pollutants in wild sea urchin
      Paracentrotus lividus.
AB  - Marine pollution has been increasing as a consequence of anthropogenic
      activities. The preservation of marine ecosystems, as well as the safety of
      harvested seafood, are nowadays a global concern. Here, we report for the first
      time the contamination levels of a large set of 99 emerging and persistent
      organic contaminants (butyltins (BTs), polycyclic aromatic hydrocarbons (PAHs),
      pesticides including pyrethroids, pharmaceuticals and personal care products
      (PCPs) and flame retardants) in roe/gonads of sea urchin Paracentrotus lividus.
      Sea urchins are a highly prized worldwide delicacy, and the harvesting of this
      seafood has increased over the last decades, particularly in South West Atlantic
      coast, where this organism is harvested mainly for exportation. Sampling was
      performed in three harvesting sites of the NW Portuguese coast subjected to
      distinct anthropogenic pressures: Carreco, Praia Norte and Vila Cha, with sea
      urchins being collected in the north and south areas of each site. Butyltins and
      pharmaceuticals were not found at measurable levels. Several PAHs, four
      pyrethroids insecticides, four PCPs and eleven flame retardants were found in
      roe/gonads of sea urchins, though in general at low levels. Differences among
      harvesting sites and between areas within each site were found, the lowest levels
      of contaminants being registered in Carreco. The accumulation of contaminants in
      sea urchins' roe/gonads seemed to reflect the low anthropogenic pressure felt in
      the sampling sites. Nevertheless, taking into account the low accumulated levels
      of chemicals, results indicate that sea urchins collected in South West Atlantic
      coast are safe for human consumption.

PMID- 29195185
TI  - Fine particulate matters: The impact of air quality standards on cardiovascular
      mortality.
AB  - BACKGROUND: In 1997 the U.S. Environmental Protection Agency set the first annual
      National Ambient Air Quality Standard (NAAQS) for fine particulate matter
      (PM2.5). Although the weight of scientific evidence has determined that a causal
      relationship exists between PM2.5 exposures and cardiovascular effects, few
      studies have concluded whether NAAQS-related reductions in PM2.5 led to
      improvements in public health. METHODS: We examined the change in cardiovascular
      (CV) mortality rate and the association between change in PM2.5 and change in CV
      mortality rate before (2000-2004) and after implementation of the 1997 annual
      PM2.5 NAAQS (2005-2010) among U.S. counties. We further examined how the
      association varied with respect to two factors related to NAAQS compliance:
      attainment status and design values (DV). We used difference-in-differences and
      linear regression models, adjusted for sociodemographic confounders. FINDINGS:
      Across 619 counties, there were 1.10 (95% CI: 0.37, 1.82) fewer CV-deaths per
      year per 100,000 people for each 1ug/m3 decrease in PM2.5. Nonattainment counties
      had a twofold larger reduction in mean annual PM2.5, 2.1ug/m3, compared to
      attainment counties, 0.97ug/m3. CV-mortality rate decreased by 0.59 (95% CI: 
      0.54, 1.71) in nonattainment and 1.96 (95% CI: 0.77, 3.15) deaths per 100,000
      people for each 1ug/m3 decrease in PM2.5 in attainment counties. When stratifying
      counties by DV, results were similar: counties with DV greater than 15ug/m3
      experienced the greatest decrease in mean annual PM2.5 (2.29ug/m3) but the
      smallest decrease in CV-mortality rate per unit decrease in PM2.5, 0.73 (95% CI: 
      0.57, 2.02). INTERPRETATION: We report a significant association between the
      change in PM2.5 and the change in CV-mortality rate before and after the
      implementation of NAAQS and note that the health benefits per 1ug/m3 decrease in
      PM2.5 persist at levels below the current national standard. FUNDING: US EPA
      intermural research.

PMID- 29195186
TI  - Medium shapes the microbial community of water filters with implications for
      effluent quality.
AB  - Little is known about the forces that determine the assembly of diverse bacterial
      communities inhabiting drinking water treatment filters and how this affects
      drinking water quality. Two contrasting ecological theories can help to
      understand how natural microbial communities assemble; niche theory and neutral
      theory, where environmental deterministic factors or stochastic factors
      predominate respectively. This study investigates the development of the
      microbial community on two common contrasting filter materials (quartz sand and
      granular activated carbon-GAC), to elucidate the main factors governing their
      assembly, through the evaluation of environmental (i.e. filter medium type) and
      stochastic forces (random deaths, births and immigration). Laboratory-scale
      filter columns were used to mimic a rapid gravity filter; the microbiome of the
      filter materials, and of the filter influent and effluent, was characterised
      using next generation 16S rRNA gene amplicon sequencing and flow-cytometry.
      Chemical parameters (i.e. dissolved organic carbon, trihalomethanes formation)
      were also monitored to assess the final effluent quality. The filter communities
      seemed to be strongly assembled by selection rather than neutral processes, with
      only 28% of those OTUs shared with the source water detected on the filter medium
      following predictions using a neutral community model. GAC hosted a
      phylogenetically more diverse community than sand. The two filter media
      communities seeded the effluent water, triggering differences in both water
      quality and community composition of the effluents. Overall, GAC proved to be
      better than sand in controlling microbial growth, by promoting higher bacterial
      decay rates and hosting less bacterial cells, and showed better performance for
      putative pathogen control by leaking less Legionella cells into the effluent
      water.

PMID- 29195187
TI  - Do worry and its associated cognitive variables alter following CBT treatment in
      a youth population with Social Anxiety Disorder? Results from a randomized
      controlled trial.

PMID- 29195188
TI  - Long-term effectiveness of cognitive behavioral therapy for youth with anxiety
      disorders.
AB  - Cognitive behavioral therapy (CBT) has demonstrated favorable long-term outcomes
      in youth with anxiety disorders in efficacy trials. However, long-term outcomes
      of CBT delivered in a community setting are uncertain. This study examined the
      long-term outcomes of individual (ICBT) and group CBT (GCBT) in youth with
      anxiety disorders treated in community mental health clinics. A total of 139
      youth (mean age at assessment 15.5 years, range 11-21 years) with a principal
      diagnosis of separation anxiety disorder (SAD), social anxiety disorder (SOP),
      and/or generalized anxiety disorder (GAD) were evaluated, on average, 3.9 years
      post-treatment (range 2.2-5.9 years). Outcomes included loss of all inclusion
      anxiety diagnoses, loss of the principal anxiety diagnosis and changes in youth-
      and parent-rated youth anxiety symptoms. At long-term follow-up, there was loss
      of all inclusion anxiety diagnoses in 53%, loss of the principal anxiety
      diagnosis in 63% of participants as well as significant reductions in all anxiety
      symptom measures. No statistical significant differences in outcome were obtained
      between ICBT and GCBT. Participants with a principal diagnosis of SOP had lower
      odds for recovery, compared to those with a principal diagnosis of SAD or GAD. In
      conclusion, outcomes of CBT for youth anxiety disorders delivered in community
      mental health clinics were improved at nearly 4 years post-treatment, and
      recovery rates at long-term follow-up were similar to efficacy trials.

PMID- 29195189
TI  - "One of the greatest medical success stories:" Physicians and nurses' small
      stories about vaccine knowledge and anxieties.
AB  - In recent years, the Canadian province of Alberta experienced outbreaks of
      measles, mumps, pertussis, and influenza. Even so, the dominant cultural
      narrative maintains that vaccines are safe, effective, and necessary to maintain
      population health. Many vaccine supporters have expressed anxieties that stories
      contradicting this narrative have lowered herd immunity levels because they
      frighten the public into avoiding vaccination. As such, vaccine policies often
      emphasize educating parents and the public about the importance and safety of
      vaccination. These policies rely on health professionals to encourage vaccine
      uptake and assume that all professionals support vaccination. Health
      professionals, however, are socially positioned between vaccine experts (such as
      immunologists) and non-experts (the wider public). In this article, I discuss
      health professionals' anxieties about the potential risks associated with
      vaccination and with the limitations of Alberta's immunisation program.
      Specifically, I address the question: If medical knowledge overwhelmingly
      supports vaccination, then why do some professionals continue to question certain
      vaccines? To investigate this topic, I interviewed twenty-seven physicians and
      seven nurses. With stock images and small stories that interviewees shared about
      their vaccine anxieties, I challenge the common assumption that all health
      professionals support vaccines uncritically. All interviewees provided generic
      statements that supported vaccination and Alberta's immunisation program, but
      they expressed anxieties when I asked for details. I found that their anxieties
      reflected nuances that the culturally dominant vaccine narrative overlooks.
      Particularly, they critiqued the influence that pharmaceutical companies, the
      perceived newness of specific vaccines, and the limitations of medical knowledge
      and vaccine schedules.

PMID- 29195190
TI  - Courtesy stigma: A concealed consternation among caregivers of people affected by
      leprosy.
AB  - This study explored experiences of courtesy stigma among caregivers of people
      affected by leprosy. Using a qualitative research approach, twenty participants
      were purposively selected and in-depth interviews conducted. The interviews were
      audio-recorded, transcribed, and analyzed to identify emerging themes that
      addressed objectives of the study. The findings indicated that caregivers of
      people affected by leprosy experienced courtesy stigma. Evidence showed that fear
      of contagion underpinned caregivers' experiences, especially in employment and
      romantic relationships. In addition, participants adopted different strategies
      (disregarding, concealment, education, faith-based trust) to handle courtesy
      stigma. The findings demonstrate that psychosocial support and financial
      assistance to caregivers are necessary considerations for attainment of effective
      care for people affected by leprosy.

PMID- 29195191
TI  - Self-disturbances, cognitive biases and insecure attachment as mechanisms of the
      relationship between traumatic life events and psychotic-like experiences in non
      clinical adults - A path analysis.
AB  - Although traumatic life events have been linked to psychotic-like experiences,
      the mechanisms of the relationship remain unclear. We investigated whether
      insecure (anxious and avoidant) attachment styles, cognitive biases and self
      disturbances serve as significant mediators in the relationship between traumatic
      life events and psychotic-like experiences in non-clinical sample. Six-hundred
      and ninety healthy participants (522 females) who have not ever been diagnosed
      with psychiatric disorders took part in the study. Participants completed self
      report scales that measure traumatic life events, psychotic-like experiences,
      cognitive biases, attachment styles and self-disturbances. Our model was tested
      with path analysis. Our integrated model fit to the data with excellent goodness
      of-fit indices. The direct effect was significantly reduced after the mediators
      were included. Significant pathways from traumatic life events to psychotic-like
      experiences were found through self-disturbances and cognitive biases. Traumatic
      life events were associated with anxious attachment through cognitive biases.
      Self-disturbances, cognitive biases and anxious attachment had a direct effect on
      psychotic-like experiences. The results of our study tentatively suggest that
      traumatic life events are related with psychotic-like experiences through
      cognitive biases and self-disturbances. Further studies in clinical samples are
      required to verify our model.

PMID- 29195192
TI  - Spectroscopic profiling and computational study of the binding of tschimgine: A
      natural monoterpene derivative, with calf thymus DNA.
AB  - DNA is a major target for a number of anticancer substances. Interaction studies
      between small molecules and DNA are essential for rational drug designing to
      influence main biological processes and also introducing new probes for the assay
      of DNA. Tschimgine (TMG) is a monoterpene derivative with anticancer properties.
      In the present study we tried to elucidate the interaction of TMG with calf
      thymus DNA (CT-DNA) using different spectroscopic methods. UV-visible absorption
      spectrophotometry, fluorescence and circular dichroism (CD) spectroscopies as
      well as molecular docking study revealed formation of complex between TMG and CT
      DNA. Binding constant (Kb) between TMG and DNA was 2.27*104M-1, that is
      comparable to groove binding agents. The fluorescence spectroscopic data revealed
      that the quenching mechanism of fluorescence of TMG by CT-DNA is static
      quenching. Thermodynamic parameters (DeltaH<0 and DeltaS<0) at different
      temperatures indicated that van der Waals forces and hydrogen bonds were involved
      in the binding process of TMG with CT-DNA. Competitive binding assay with
      methylene blue (MB) and Hoechst 33258 using fluorescence spectroscopy displayed
      that TMG possibly binds to the minor groove of CT-DNA. These observations were
      further confirmed by CD spectral analysis, viscosity measurements and molecular
      docking.

PMID- 29195193
TI  - Vibrational spectroscopic characterization of cyclic and acyclic molecular rotors
      with 1,4-diethynylphenylene-d4 rotators.
AB  - The synthesis and characterization of acyclic and cyclic molecular rotors with
      1,4-diethynylphenylene-d4 rotators are described. The ATR-FTIR and Raman spectra
      of acyclic rotor 3 and cyclic rotor 5E were measured and interpreted. A feature
      of ATR-FTIR spectrum of rotor 5E is a strong two-component band around 1730cm-1
      attributed to symmetric and asymmetric stretching vibration of the carbonyl
      group, while this is not observed in rotor 3. Raman investigation in the wide
      temperature range of 350 - 10K was carried out. The splitting of Raman bands in
      the region of stretching vibration of CC double and triple bonds at 170 and 260K
      for rotor 5E is observed. The splitting of bands is due to changes in molecular
      structure.

PMID- 29195194
TI  - Oxygenic denitrification for nitrogen removal with less greenhouse gas emissions:
      Microbiology and potential applications.
AB  - Nitrogen pollution is a worldwide problem and has been extensively treated by
      canonical denitrification (CDN) process. However, the CDN process generates
      several issues such as intensive greenhouse gas (GHG) emissions. In the past
      years, a novel biological nitrogen removal (BNR) process of oxygenic
      denitrification (O2DN) has been proposed as a promising alternative to the CDN
      process. The classic denitrification four steps are simplified to three steps by
      O2DN bacteria without producing and releasing the intermediate nitrous oxide
      (N2O), a potent GHG. In this article, we summarized the findings in previous
      literatures as well as our results, including involved microorganisms and
      metabolic mechanisms, functional genes and microbial detection, kinetics and
      influencing factors and their potential applications in wastewater treatment.
      Based on our knowledge and experience, the benefits and limitations of the
      current O2DN process were analyzed. Since O2DN is a new field in wastewater
      treatment, more research and application is required, especially the development
      of integrated processes and the quantitative assessment of the contribution of
      O2DN process in natural habitats and engineered systems.

PMID- 29195195
TI  - Economic impacts of urban flooding in South Florida: Potential consequences of
      managing groundwater to prevent salt water intrusion.
AB  - High-value urban zones in coastal South Florida are considered particularly
      vulnerable to salt water intrusion into the groundwater-based, public water
      supplies caused by sea level rise (SLR) in combination with the low topography,
      existing high water table, and permeable karst substrate. Managers in the region
      closely regulate water depths in the extensive South Florida canal network to
      control closely coupled groundwater levels and thereby reduce the risk of
      saltwater intrusion into the karst aquifer. Potential SLR adaptation strategies
      developed by local managers suggest canal and groundwater levels may have to be
      increased over time to prevent the increased salt water intrusion risk to
      groundwater resources. However, higher canal and groundwater levels cause the
      loss of unsaturated zone storage and lead to an increased risk of inland flooding
      when the recharge from rainfall exceeds the capacity of the unsaturated zone to
      absorb it and the water table reaches the surface. Consequently, higher canal and
      groundwater levels are also associated with increased risk of economic losses,
      especially during the annual wet seasons. To help water managers and urban
      planners in this region better understand this trade-off, this study models the
      relationships between flood insurance claims and groundwater levels in Miami-Dade
      County. Via regression analyses, we relate the incurred number of monthly flood
      claims in 16 Miami-Dade County watersheds to monthly groundwater levels over the
      period from 1996 to 2010. We utilize these estimated statistical relationships to
      further illustrate various monthly flood loss scenarios that could plausibly
      result, thereby providing an economic quantification of a "too much water" trade
      off. Importantly, this understanding is the first of its kind in South Florida
      and is exceedingly useful for regional-scale hydro-economic optimization models
      analyzing trade-offs associated with high water levels.

PMID- 29195196
TI  - Adaptation of Gammarus pulex to agricultural insecticide contamination in
      streams.
AB  - Exposure to pesticides affects non-target aquatic communities, with substantial
      consequences on ecosystem services. Adaptation of exposed populations may reduce
      the effects of pesticides. However, it is not known under which conditions
      adaptation occurs when only a low toxic pressure from pesticides is present.
      Here, we show that Gammarus pulex, a dominant macroinvertebrate species in many
      agricultural streams, acquires increased tolerance to pesticides when
      recolonization from non-contaminated refuge areas is low. Populations in the
      field that were exposed to pesticides at concentrations several orders of
      magnitude below considerable acute effects showed almost 3-fold higher tolerance
      to the neonicotinoid insecticide clothianidin (mean EC50 218MUgL-1) compared with
      non-exposed populations (mean EC50 81MUgL-1). This tolerance of exposed
      populations increased from 2- to 4-fold with increasing distance to the next
      refuge area (0 to 10km). We conclude that the development of tolerance for non
      target species may occur at very low concentrations, much below those affecting
      sensitive test organisms and also lower than those predicted to be safe by
      governmental risk assessment frameworks.

PMID- 29195197
TI  - Microbial decomposition is highly sensitive to leaf litter emersion in a
      permanent temperate stream.
AB  - Drought frequency and intensity in some temperate regions are forecasted to
      increase under the ongoing global change, which might expose permanent streams to
      intermittence and have severe repercussions on stream communities and ecosystem
      processes. In this study, we investigated the effect of drought duration on
      microbial decomposition of Populus nigra leaf litter in a temperate permanent
      stream (Oliveira, NW Portugal). Specifically, we measured the response of the
      structural (assemblage composition, bacterial and fungal biomass) and functional
      (leaf litter decomposition, extracellular enzyme activities (EEA), and fungal
      sporulation) parameters of fungal and bacterial communities on leaf litter
      exposed to emersion during different time periods (7, 14 and 21d). Emersion time
      affected microbial assemblages and litter decomposition, but the response
      differed among variables. Leaf decomposition rates and the activity of beta
      glucosidase, cellobiohydrolase and phosphatase were gradually reduced with
      increasing emersion time, while beta-xylosidase reduction was similar when
      emersion last for 7 or more days, and the phenol oxidase reduction was similar at
      14 and 21days of leaf emersion. Microbial biomass and fungal sporulation were
      reduced after 21days of emersion. The structure of microbial assemblages was
      affected by the duration of the emersion period. The shifts in fungal assemblages
      were correlated with a decreased microbial capacity to degrade lignin and
      hemicellulose in leaf litter exposed to emersion. Additionally, some resilience
      was observed in leaf litter mass loss, bacterial biomass, some enzyme activities
      and structure of fungal assemblages. Our study shows that drought can strongly
      alter structural and functional aspects of microbial decomposers. Therefore, the
      exposure of leaf litter to increasing emersion periods in temperate streams is
      expected to affect decomposer communities and overall decomposition of plant
      material by decelerating carbon cycling in streams.

PMID- 29195198
TI  - Single microbial fuel cell reactor for coking wastewater treatment: Simultaneous
      carbon and nitrogen removal with zero alkaline consumption.
AB  - The use of several individual reactors for sequential removal of organic
      compounds and nitrogen, in addition to the required alkaline addition in aerobic
      reactors, remain outstanding technical challenges to the traditional biological
      treatment of coking wastewater. Here, we report the utilization of a single
      microbial fuel cell (MFC) reactor that performs simultaneous carbon and nitrogen
      removal with zero alkaline consumption, as evidenced by the results of the batch
      fed and continuous-flow experiments. The MFC exhibited faster reaction kinetics
      for COD and total nitrogen (TN) removal than the same configured reactor
      analogous to the traditional aerobic biological reactor (ABR). At a hydraulic
      retention time (HRT) of 125 h, the efficiencies of COD and TN removal in the MFC
      reached 83.8+/-3.6% and 97.9+/-2.1%, respectively, much higher than the values of
      73.8+/-2.9% and 50.2+/-5.0% obtained in the ABR. Furthermore, the degradation in
      the MFC of the main organic components, including phenolic compounds (such as
      phenol, 2-methylphenol, 3-methylphenol, 4-methylphenol, and 2,4-dimethlyphenol)
      and nitrogenous heterocyclic compounds (such as quinolone, pyridine, indole, and
      isoquinolone) was greater than that in the ABR. The enhancing effect was
      attributed to the ability of the MFC to self-adjust the pH. It was also
      manifested by the increased abundances of heterotrophs, nitrifiers, and
      denitrifiers in the MFC. The correlations between the current density and the
      rates of COD and TN removal suggest that the extent of the current from the anode
      to the cathode is a critical parameter for the overall performance of MFCs in the
      treatment of coking wastewater.

PMID- 29195199
TI  - Comparison of parameterizations for the atmospheric extinction coefficient in
      Lin'an, China.
AB  - A more precise atmospheric extinction coefficient would be advantageous for
      improving air quality (visibility) forecasting. In this study, the size
      distribution, chemical composition and relative humidity were measured in Lin'an
      from January 9 to 31, 2015. The merits and weaknesses of three parameterization
      schemes are discussed in this paper, including the non-linear fitting scheme, the
      IMPROVE (Interagency Monitoring of Protected Visual Environment) algorithm and
      the kappa-elemental carbon (EC)-Mie model. Comparing the three schemes mentioned
      above, we find that the non-linear fitting equation requires the least amount of
      data, and its calculation process is the simplest. However, its calculated values
      are significantly influenced by specific data and fitting formulas. The
      uncertainty of the variable coefficients makes it difficult to directly implement
      this method for other datasets. The calculated values of the three versions of
      the IMPROVE algorithm strongly correlate with the measured values, with slopes
      near 1.0 and statistical indexes (R2) of 0.848, 0.858 and 0.866. However, this
      method is affected by the chemical compositions of the particles in different
      regions; for example, when the quality of PM2.5 is reconstructed from the
      measured data, the coefficients of different components change, thus affecting
      the final results. The kappa-EC-Mie model objectively reflects the changes in the
      law of visibility, as the model considers both the chemical composition and size
      distribution of particles, and its predominant merit is derived from the fact
      that it is calculated without an empirical formula, which may eliminate the
      computational errors caused by the uncertainties of coefficients.

PMID- 29195200
TI  - Spatial distribution and seasonal variation of four current-use pesticides (CUPs)
      in air and surface water of the Bohai Sea, China.
AB  - Current-use pesticides (CUPs) are widely used in agriculture, and some are listed
      as persistent organic pollutants (POPs) due to their bioaccumulative and toxic
      properties. China is one of the largest producers and users of pesticides in the
      world. However, very limited data are available about the environmental fates of
      CUPs. Four CUPs (trifluralin, chlorothalonil, chlorpyrifos, and dicofol) in
      surface seawater and low atmospheric samples taken during research cruises on the
      Bohai Sea in August and December 2016 and February 2017 were analyzed, we added
      the spring data sampled in May 2012 to the discussion of seasonal variation. In
      our study, chlorpyrifos was the most abundant CUPs in the gas phase with a mean
      abundance of 59.06+/-126.94pgm-3, and dicofol had the highest concentration
      dissolved in seawater (mean: 115.94+/-123.16pgL-1). The concentrations of all
      target compounds were higher during May and August due to intensive use and
      relatively high temperatures in the spring and summer. Backward trajectories
      indicated that air masses passing through the eastern coast of the Bohai Sea
      contained high concentrations of pollutants, while the air masses from the Bohai
      and Yellow Seas were less polluted. The high concentration of pollutants in
      seawater was not only influenced by high yields from the source region of
      production or usage, but also by input from polluted rivers. Volatilization from
      surface water was found to be an important source of trifluralin and chlorpyrifos
      in the air. Air-sea gas exchange of chlorothalonil underwent strong net
      deposition (mean FRs: 51.67), which was driven by higher concentrations in air
      and indicates that the Bohai Sea acted as a sink for chlorothalonil.

PMID- 29195201
TI  - A fuzzy multicriteria categorization of the GALDIT method to assess seawater
      intrusion vulnerability of coastal aquifers.
AB  - Groundwater constitutes the primary source of fresh water for >1.2 billion people
      living in coastal zones. However, the threat of seawater intrusion is widespread
      in coastal aquifers mainly due to overexploitation of groundwater. In the present
      study, a modified fuzzy multicriteria categorization into non-ordered categories
      method was developed in order to modify the standard GALDIT method and assess
      seawater intrusion vulnerability in a coastal aquifer of northern Greece. The
      method is based on six parameters: groundwater occurrence, aquifer hydraulic
      conductivity, groundwater level, distance from the shore, impact of the existing
      status of seawater intrusion, and aquifer thickness. Initially, the original
      method was applied and revealed a zone of high vulnerability running parallel to
      the coastline and covering an area of 8.6km2. The modified GALDIT-F method
      achieved higher discretization of vulnerability zones which is essential to build
      a rational management plan to prevent seawater intrusion. The GALDIT-F approach
      also distinguished an area of the aquifer that is influenced by geothermal
      fluids. In total, twenty-five categories were produced corresponding to different
      vulnerability degrees according to the initial method (High, Moderate, Low) as
      well as the area influenced by geothermal fluids. Finally, a road map was
      developed in order to adapt management strategies to GALDIT-F categories and
      prevent and mitigate seawater intrusion. The proposed management strategies of
      the coastal aquifer include managed aquifer recharge (MAR) implementation,
      reallocation of existing wells, optimization of pumping rates during the
      hydrological year, and a detailed monitoring plan.

PMID- 29195202
TI  - Exportation of dissolved (inorganic and organic) and particulate carbon from
      mangroves and its implication to the carbon budget in the Indian Sundarbans.
AB  - Mangroves are known for exchanging organic and inorganic carbon with estuaries
      and oceans but studies that have estimated their contribution to the global
      budget are limited to a few mangrove ecosystems which exclude world's largest the
      Sundarbans. Here, we worked in the Indian Sundarbans and in the Hooghly
      river/estuary in May (pre-monsoon) and December (post-monsoon), 2014. Aims were,
      i) to quantify the riverine export of particulate organic carbon (POC) and
      dissolved organic and inorganic carbon (DOC, DIC)) of the Hooghly into the Bay of
      Bengal (BoB), ii) to estimate the C export (DOC, DIC, POC) from the Sundarbans
      into the BoB by using a simple mixing model, as well as iii) to revise the
      existing C budget constructed for the mangroves. The riverine exports of POC, DOC
      and DIC account for 0.07TgCyr-1, 0.34TgCyr-1 and 4.14TgCyr-1, respectively, and
      were largest during the monsoon period. Results revealed that mangrove plant
      derived organic matter and its subsequent degradation is the primary source of
      DIC and DOC in the Hooghly estuary whereas POC is linked to soil erosion.
      Mangroves are identified as a major source of carbon (POC, DOC, DIC) transported
      from the Sundarbans into the BoB, with export rates of 0.58 TgCyr-1, 3.03TgCyr-1,
      and 3.69TgCyr-1 respectively, altogether amounting to 7.3TgCyr-1. This C export
      from the Indian Sundarbans exceeds the 'missing C' of the previous budget, thus
      necessitating further research to finally resolve the mangrove C budget. However,
      these first baseline data on C exports from the world's largest deltaic mangrove
      improves limited global data inventory and signifies the need of acquiring more
      data from different mangrove settings to reduce uncertainties.

PMID- 29195203
TI  - Environmental forcing on the flux of organic-walled dinoflagellate cysts in
      recent sediments from a subtropical lagoon in the Gulf of California.
AB  - To evaluate the relationship of changes in organic-walled dinoflagellate cyst
      (dinocyst) fluxes to sediments with environmental variables (air and sea surface
      temperatures, El Nino conditions, rainfall, and terrigenous index), cyst
      assemblages were analyzed in a 210Pb-dated sediment core (~100years) from the
      pristine San Jose Lagoon (San Jose Island, SW Gulf of California). The dinocyst
      abundance ranged from 3784 to 25,108cystsg-1 and fluxes were of the order of 103
      104cystscm-2yr-1. Lingulodinium machaerophorum, Polysphaeridium zoharyi and
      Spiniferites taxa accounted for 96% of the total dinocyst assemblages, and the
      abundances of these species increased towards the core surface. P. zoharyi fluxes
      increased from about 1965 onwards. Redundancy analyses, showed that mean minimum
      air temperature and terrigenous index were the key factors governing dinocyst
      fluxes. In this study, dinocyst fluxes of dominant taxa had responded to changes
      in climate-dependent environmental variables during the past ~20years; this may
      also be the case in other subtropical coastal lagoons.

PMID- 29195204
TI  - Trace elements in PM2.5 in Shandong Province: Source identification and health
      risk assessment.
AB  - The chemical compositions in PM2.5 in metropolitan areas have obtained lots of
      attentions, of which concerns of airborne trace elements are relatively lacking.
      Here, PM2.5 samples were collected simultaneously in one year at four urban sites
      (Zibo (ZB), Zaozhuang (ZZ), Qingdao (QD) and Jinan (JN (Shandong University)),
      and a rural site (JN (Miaopu)) in Shandong province. 25 elements (Al, Na, Cl, Mg,
      Si, S, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br, Sr, Cd, Ba and
      Pb) in PM2.5 were measured by wavelength dispersive X-ray fluorescence
      spectrometer (WDXRF). Most trace elements (Al, Na, Cl, Mg, Si, Ca, Ti, Mn, Fe,
      Co, Ni, As, Se, Br, Cd, Ba and Pb) exhibited the highest levels at ZB and the
      lowest at QD. Meanwhile, they presented obvious seasonal variations with the
      highest concentrations in winter or spring and the lowest in summer. S and K were
      the most abundant elements in the area. In the non-crustal trace metal elements,
      Zn, Pb and Mn presented the highest concentrations. Positive matrix factorization
      (PMF) modeling revealed that secondary formation, coal combustion and industry
      emissions were the main sources in the region. The health risk assessments
      suggested that at the five sites Cd (diet) for adults, Pb and Co for children,
      and Mn (diet) for both adults and children (at ZB and SDU sites) had non
      carcinogenic risks. As and Pb for adults and children existed carcinogenic risks,
      especially Pb for children. The sources of these elements with health risks were
      further explored. Notably, Cd, As and Pb should be paid special attention in the
      area due to their high concentrations in aerosol water exceeding the acceptable
      health risks, especially Pb.

PMID- 29195205
TI  - Distribution of phthalates in Marseille Bay (NW Mediterranean Sea).
AB  - Phthalic Acid Esters (PAEs) are a group of emerging organic contaminants that
      have become a serious issue because of their ubiquitous presence and hazardous
      impact on the marine environment worldwide. Seawater samples were collected
      monthly from December 2013 to November 2014 in the northwestern Mediterranean Sea
      (Marseille Bay). The samples were analyzed for dissolved organic carbon (DOC) as
      well as the molecular distribution of dissolved PAEs by using solid phase
      extraction followed by gas chromatography and mass spectrometry (GC/MS) analyses.
      The results demonstrated the occurrence of six PAEs, including dimethyl phthalate
      (DMP), diethyl phthalate (DEP), di-isobutyl phthalate (DiBP), di-n-butyl
      phthalate (DnBP), benzylbutyl phthalate (BzBP) and diethylhexyl phthalate (DEHP),
      with total concentrations ranging from 130 to 1330ngL-1 (av. 522ngL-1). In
      Marseille Bay, the highest concentrations were detected in the bottom water from
      June to November 2014 and in the whole water column during the winter mixing
      period. This result suggests that resuspension of PAE-rich sediment, in relation
      to the accumulation of plastic debris above the seabed, or the higher degradation
      rate in the upper layer of the water column, plays a significant role in the PAE
      dynamics in coastal water. DEHP was the most abundant PAE in all of the surface
      samples and the summer bottom samples, followed by DiBP and DnBP, which also
      represent the largest fractions in the other bottom samples.

PMID- 29195206
TI  - Effects of changing climate on European stream invertebrate communities: A long
      term data analysis.
AB  - Long-term observations on riverine benthic invertebrate communities enable
      assessments of the potential impacts of global change on stream ecosystems.
      Besides increasing average temperatures, many studies predict greater temperature
      extremes and intense precipitation events as a consequence of climate change. In
      this study we examined long-term observation data (10-32years) of 26 streams and
      rivers from four ecoregions in the European Long-Term Ecological Research (LTER)
      network, to investigate invertebrate community responses to changing climatic
      conditions. We used functional trait and multi-taxonomic analyses and combined
      examinations of general long-term changes in communities with detailed analyses
      of the impact of different climatic drivers (i.e., various temperature and
      precipitation variables) by focusing on the response of communities to climatic
      conditions of the previous year. Taxa and ecoregions differed substantially in
      their response to climate change conditions. We did not observe any trend of
      changes in total taxonomic richness or overall abundance over time or with
      increasing temperatures, which reflects a compensatory turnover in the
      composition of communities; sensitive Plecoptera decreased in response to warmer
      years and Ephemeroptera increased in northern regions. Invasive species increased
      with an increasing number of extreme days which also caused an apparent upstream
      community movement. The observed changes in functional feeding group diversity
      indicate that climate change may be associated with changes in trophic
      interactions within aquatic food webs. These findings highlight the vulnerability
      of riverine ecosystems to climate change and emphasize the need to further
      explore the interactive effects of climate change variables with other local
      stressors to develop appropriate conservation measures.

PMID- 29195207
TI  - Spatial diversification of agroecosystems to enhance biological control and other
      regulating services: An agroecological perspective.
AB  - Spatial diversification of crop and non-crop habitats in farming systems is
      promising for enhancing natural regulation of insect pests. Nevertheless, results
      from recent syntheses show variable effects. One explanation is that the
      abundance and diversity of pests and natural enemies are affected by the
      composition, design and management of crop and non-crop habitats. Moreover,
      interactions between both local and landscape elements and practices carried out
      at different spatial scales may affect the regulation of insect pests. Hence,
      research is being conducted to understand these interdependencies. However,
      insects are not the only pests and pests are not the only elements to regulate in
      agroecosystems. Broadening the scope could allow addressing multiple issues
      simultaneously, but also solving them together by enhancing synergies. Indeed,
      spatial diversification of crop and non-crop habitats can allow addressing the
      issues of weeds and pathogens, along with being beneficial to several other
      regulating services like pollination, soil conservation and nutrient cycling.
      Although calls rise to develop multifunctional landscapes that optimize the
      delivery of multiple ecosystem services, it still represents a scientific
      challenge today. Enhancing interdisciplinarity in research institutions and
      building interrelations between scientists and stakeholders may help reach this
      goal. Despite obstacles, positive results from research based on such innovative
      approaches are encouraging for engaging science in this path. Hence, the aim of
      the present paper is to offer an update on these issues by exploring the most
      recent findings and discussing these results to highlight needs for future
      research.

PMID- 29195208
TI  - Validation of Arxula Yeast Estrogen Screen assay for detection of estrogenic
      activity in water samples: Results of an international interlaboratory study.
AB  - Endocrine-active substances can adversely impact the aquatic ecosystems. A
      special emphasis is laid, among others, on the effects of estrogens and estrogen
      mimicking compounds. Effect-based screening methods like in vitro bioassays are
      suitable tools to detect and quantify endocrine activities of known and unknown
      mixtures. This study describes the validation of the Arxula-Yeast Estrogen Screen
      (A-YES(r)) assay, an effect-based method for the detection of the estrogenic
      potential of water and waste water. This reporter gene assay, provided in ready
      to use format, is based on the activation of the human estrogen receptor alpha.
      The user-friendly A-YES(r) enables inexperienced operators to rapidly become
      competent with the assay. Fourteen laboratories from four countries with
      different training levels analyzed 17beta-estradiol equivalent concentrations
      (EEQ) in spiked and unspiked waste water effluent and surface water samples, in
      waste water influent and spiked salt water samples and in a mixture of three
      bisphenols. The limit of detection (LOD) for untreated samples was 1.8ng/L 17beta
      estradiol (E2). Relative repeatability and reproducibility standard deviation for
      samples with EEQ above the LOD (mean EEQ values between 6.3 and 20.4ng/L) ranged
      from 7.5 to 21.4% and 16.6 to 28.0%, respectively. Precision results are
      comparable to other frequently used analytical methods for estrogens. The A
      YES(r) has been demonstrated to be an accurate, precise and robust bioassay. The
      results have been included in the ISO draft standard. The assay was shown to be
      applicable for testing of typical waste water influent, effluent and saline
      water. Other studies have shown that the assay can be used with enriched samples,
      which lower the LOD to the pg/L range. The validation of the A-YES(r) and the
      development of a corresponding international standard constitute a step further
      towards harmonized and reliable bioassays for the effect-based analysis of
      estrogens and estrogen-like compounds in water samples.

PMID- 29195209
TI  - Daphnia magna filtration efficiency and mobility in laminar to turbulent flows.
AB  - Daphnia are filter feeder organisms that prey on small particles suspended in the
      water column. Since Daphnia individuals can feed on wastewater particles, they
      have been recently proposed as potential organisms for tertiary wastewater
      treatment. However, analysing the effects of hydrodynamics on Daphnia individuals
      has scarcely been studied. This study focuses then, on quantifying the filtration
      and swimming velocities of D. magna individuals under different hydrodynamic
      conditions. Both D. magna filtration and movement responded differently if the
      flow was laminar or if it was turbulent. In a laminar-dominated flow regime
      Daphnia filtration was enhanced up to 2.6 times that of a steady flow, but in the
      turbulent-dominated flow regime D. magna filtration was inhibited. In the laminar
      flow regime D. magna individuals moved freely in all directions, whereas in the
      turbulent flow regime they were driven by the streamlines of the flow. A model
      based on Daphnia-particle encountering revealed that the filtration efficiency in
      the laminar regime was driven by the length of the D. magna individuals and the
      shear rate imposed by the system.

PMID- 29195210
TI  - Influence of undergraduate nursing student teaching methods on learning standard
      precautions and transmission-based precautions: Experimental research.
AB  - OBJECTIVES: An experimental study was performed with undergraduate nursing
      students in order to determine, between two methodologies, which is the best for
      learning standard precautions and precautions based on disease transmission
      mechanisms. METHODS: Students in the sample are stratified by performance, with
      the experimental group (49 students) being exposed to self-instruction and
      clinical simulation on the topic of standard precautions and special precautions
      according to disease transmission mechanisms. Conventional classes on the same
      topics were provided to the control group (49 students). RESULTS: The
      experimental group showed the best performance in the multiple-choice post-test
      of knowledge (p=0.002) and in the assessment of essay questions (p=0.043), as
      well as in the evaluation of a simulated scenario, in relation to the control
      group. CONCLUSIONS: This study demonstrates that it is possible to transfer some
      teaching subjects on the prevention of Healthcare Associated Infections (HAIs) to
      self-learning by means of virtual teaching strategies with good results. This
      allows greater efficiency in the allocation of teachers to clinical simulation or
      learning situations in the laboratory, where students can apply what they have
      learned in the self-instruction module.

PMID- 29195211
TI  - Supporting those who work and learn: A phenomenological research study.
AB  - AIM: With a shift in the United Kingdom's National Health Service to
      organisational learning and the local introduction of the Assistant Practitioner
      role to support the nursing workforce there was a broad need to understand the
      lived experiences of those who work and learn. METHOD: Hermeneutic phenomenology
      was the chosen methodology. A purposive sample of eight trainee assistant
      practitioners, four matrons, seven mentors and the practice development nurse
      participated in conversational interviews at intermittent points in the journey.
      RESULTS: A stepped process of analysis produced three over-arching super-ordinate
      themes which indicated that the transition to assistant practitioner is non
      linear and complex necessitating a change in knowledge and behaviour and the
      workplace culture must enable learning and role development. This paper focuses
      on supporting the journey which encompassed learning at university and learning
      in the workplace. CONCLUSION: Participants' stories demonstrated the presence of
      knowledgeable mentors and a learning culture enabled new roles to be supported.

PMID- 29195212
TI  - An evaluation into the impact of undergraduate nursing students classroom
      attendance and engagement with online tasks on overall academic achievement.

PMID- 29195213
TI  - Nursing students' emotional intelligence, coping styles and learning satisfaction
      in clinically simulated palliative care scenarios: An observational study.
AB  - BACKGROUND: Emotional intelligence is highly relevant in palliative care
      training, considering the coping styles used by nursing students. Clinical
      simulation provides the opportunity to evaluate these variables in a realistic
      and natural context. OBJECTIVES: To analyze the possible relation between
      emotional intelligence, coping styles and satisfaction with one's own self
      learning in nursing students participating in simulated scenarios related to
      palliative care at the end of life. METHODS: A descriptive, observational and
      correlational study of students in their second year of nursing at a Spanish
      University during the 2015/2016 academic year. Three variables were measured:
      emotional intelligence (Trait Meta-Mood Scale-24), coping styles (the
      Questionnaire for Dealing with Stress) and satisfaction with students' own
      learning (Student Satisfaction and Self-Confidence in Learning Scale, Spanish
      version CSLS-Sv). RESULTS: In total, 74 students participated in this study (ME:
      20.3years). An association was found between satisfaction with learning,
      according to the EI attention subscale (in which the highest scores were
      registered) and two specific coping styles (FSP, with high scores and open
      emotional expression). CONCLUSIONS: Emotional intelligence and coping styles are
      desirable qualities in students, especially as they have a relevant role in
      satisfaction with one's own learning. Nonetheless, in part, these results depend
      on the characteristics of the educational activities designed, which is
      especially relevant in simulation applied to palliative care.

PMID- 29195214
TI  - Photoluminescent reduced graphene oxide quantum dots from latex of Calotropis
      gigantea for metal sensing, radical scavenging, cytotoxicity, and bioimaging in
      Artemia salina: A greener route.
AB  - In this work, we report the fabrication of green fluorescent reduced graphene
      oxide quantum dots (rGOQDs) from the latex of Calotropis gigantea by simple one
      step microwave assisted greener route. The latex of Calotropis gigantea calcined
      at 300 degrees C and its ethanolic extract is used for the synthesis of QDs, The
      rGOQDs showed particle size ranging from 2 to 8nm and it exhibited green
      fluorescent in longer UV region at 360-520nm. The rGOQDs graphitic nature was
      confirmed by RAMAN and XRD analysis. The FTIR, XPS demonstrate that presence of
      functional groups such as CO, COC, -OH, hence it's addressing them as rGOQDs. It
      is used to design the greener and economically adopted fluorescent probe for the
      detection of Pb2+ ions. It provides simple and appropriate for the selective and
      sensitive detection of Pb2+ ions in water purification process. It also trapped
      the free radicals and neutralized that and act as an excellent radical scavenger
      in DPPH radical scavenging assessment. These rGOQDs showed excellent
      biocompatibility on brine shrimp nauplii (Artemia salina) up to 160MUg/mL for 24h
      incubation. Furthermore, rGOQDS were demonstrated as fluorescent bioimaging probe
      selectively in the inner digestion part of Artemia salina. In summary, stable,
      economically viable, highly biocompatible, greener method based rGOQDs were
      prepared for heavy metal ion detecting, radical scavenging, bioimaging
      applications which can play a vital role in the future nanotechnology-based
      biomedical field.

PMID- 29195215
TI  - Amberlite IR-120 (H) mediated "on water" synthesis of fluorescent Ruthenium(II)
      arene 8-hydroxyquinoline complexes for cancer therapy and live cell imaging.
AB  - A series of Ruthenium-Quinolinol complexes (3a-d &4a-d) has been synthesized by
      employing a simple, efficient and environmental friendly condition. Catalytic
      role of Amberlite IRA-120(H) has been demonstrated. The structures of the new
      compounds were elucidated by the analysis of spectroscopic data. The stability of
      these complexes was measured by UV spectroscopy & time dependent NMR
      spectroscopy. These newly developed complexes were represented as potential
      anticancer agent against human breast carcinoma cell line (MCF-7), human
      Epitheloid Cervix Carcinoma (HeLa), human lung adenocarcinoma epithelial cell
      line (A549) and human colon cancer cell line (Caco-2). Most of the ruthenium
      complexes showed higher anticancer activity in MCF-7, HeLa and Caco-2 cell lines
      than cisplatin. A high selectivity (9-28 folds) was observed with these newly
      developed organoruthenium compounds in human cancer cell lines (MCF-7, HeLa and
      Caco-2) with respect to normal fibroblast cell line (MRC-5). Complex [(eta6
      hexamethylbenzene)RuCl(kappa2-O,N-5-chloro-HyQ)].Cl (4b), [(eta6
      hexamethylbenzene)RuCl(kappa2-O,N-5,7-dibromo-HyQ)].Cl (4c) and [(eta6
      hexamethylbenzene)RuCl(kappa2-O,N-5-chloro-7-iodo-HyQ)].Cl (4d) exhibited best
      cytotoxicity profiles in three reported human cancer cell lines (MCF-7, HeLa,
      Caco-2). Cellular imaging study was also performed with these newly developed
      organoruthenium compounds. Compound 4c might be utilized for cancer theranostic
      agents because of its significant quantum yield in water, high potency,
      selectivity and high cellular uptake in cancer cell lines.

PMID- 29195216
TI  - Photo-induced toxicity of tungsten oxide photochromic nanoparticles.
AB  - We synthesised a new type of photochromic tungsten oxide nanoparticles, analysed
      their photocatalytic activity and carried out a thorough analysis of their effect
      on prokaryotic and eukaryotic organisms. Ultrasmall hydrated tungsten oxide
      nanoparticles were prepared by means of hydrothermal treatment of tungstic acid
      in the presence of polyvinylpyrrolidone as a template, stabiliser and growth
      regulator. Tungstic acid was synthesised through an ion-exchange method using
      sodium tungstate solution and a strongly acidic cation exchange resin. Upon
      illumination, photochromic nanoparticles of WO3 were shown to increase greatly
      their toxicity against both bacterial (both gram-positive and gram-negative - P.
      aeruginosa, E. coli and S. aureus) and mammalian cells (primary mouse embryonic
      fibroblasts); under the same conditions, fungi (C. albicans) were less sensitive
      to the action of tungsten oxide nanoparticles. UV irradiation of primary mouse
      fibroblasts in the presence of WO3 nanoparticles demonstrated a time- and dose
      dependent toxic effect, the latter leading to a significant decrease in
      dehydrogenase activity and an increase in the number of dead cells. WO3
      nanoparticles were photocatalytically active under both UV light and even
      diffused daylight filtered through a window glass, leading to indigo carmine
      organic dye discolouration. The obtained experimental data not only show good
      prospects for biomedical applications of tungsten trioxide, but also demonstrate
      the need for clear control of biosafety when it is used in various household
      materials and appliances.

PMID- 29195217
TI  - Effects of posture and anatomical location on inter-recti distance measured using
      ultrasound imaging in parous women.
AB  - STUDY DESIGN: Cross-sectional repeated measures. OBJECTIVES: To quantify the
      effects of posture and measurement site on the inter-recti distance (IRD) and
      investigate the reliability of IRD measurement using ultrasound imaging in
      different postures. BACKGROUND: The linea alba connects the rectus abdominis
      muscles anteriorly and the width is known as the IRD. The IRD is usually measured
      in crook-lying and is the primary outcome measure to assess for a divarication of
      recti abdominis (DRA). The effects of posture and measurement site on the IRD
      have not been investigated. METHODS: Ultrasound imaging was used to measure IRD
      in 41 women >=8 weeks postpartum. The IRD was measured at three sites (superior
      umbilicus, umbilicus and inferior-umbilicus), in three postures (crook-lying,
      sitting and standing), and repeated one-week later. The effects of posture and
      site were investigated using one-way ANOVAs. Reliability was analysed using
      Intraclass correlation coefficients (ICCs), Bland Altman analyses, standard error
      of measurement and minimal detectable change. RESULTS: The IRD was wider when
      standing vs. lying at both the superior-umbilicus and umbilicus by 0.30 cm (95%
      CI 0.21 to 0.39) and 0.20 cm (0.11-0.30) respectively (p < 0.001). Measurements
      at the inferior-umbilicus were, on average, 1.6 and 2.1 cm narrower than superior
      umbilicus and umbilicus sites, respectively (p < 0.001). There was high intra
      rater reliability within-session (ICC3.3) and between-session (ICC3.1) at all
      sites measured. CONCLUSION: The IRD can be measured reliably at all sites and
      postures. The IRD is wider at superior-umbilicus and umbilicus when upright
      compared with lying. There is a difference in IRD between all sites measured.

PMID- 29195218
TI  - Nucleic acid-based electrochemical nanobiosensors.
AB  - The detection of biomarkers using sensitive and selective analytical devices is
      critically important for the early stage diagnosis and treatment of diseases. The
      synergy between the high specificity of nucleic acid recognition units and the
      great sensitivity of electrochemical signal transductions has already shown
      promise for the development of efficient biosensing platforms. Yet nucleic-acid
      based electrochemical biosensors often rely on target amplification strategies
      (e.g., polymerase chain reactions) to detect analytes at clinically relevant
      concentration ranges. The complexity and time-consuming nature of these
      amplification methods impede moving nucleic acid-based electrochemical biosensors
      from laboratory-based to point-of-care test settings. Fortunately, advancements
      in nanotechnology have provided growing evidence that the recruitment of
      nanoscaled materials and structures can enhance the biosensing performance
      (particularly in terms of sensitivity and response time) to the level suitable
      for use in point-of-care diagnostic tools. This Review highlights the significant
      progress in the field of nucleic acid-based electrochemical nanobiosensing with
      the focus on the works published during the last five years.

PMID- 29195219
TI  - Nanoconjugates of ferrocene and carbon-encapsulated iron nanoparticles as sensing
      platforms for voltammetric determination of ceruloplasmin in blood.
AB  - The nanoparticles comprising of iron core and carbon shell were decorated with
      ferrocene derivatives: ferrocenecarboxaldehyde (Fc-1) and ferrocenecarboxaldehyde
      oxime (Fc-2). A microdrop of suspension of the nanoconjugate was placed on a
      glassy-carbon electrode to prepare the recognition/sensing layer. Drying and
      purification of the sensing layer resulted in a well-defined and stable square
      wave voltammogram of the ferrocene moiety. The height of the voltammetric peak
      increased in the presence of ceruloplasmin. That increase was linearly dependent
      on the logarithmic concentration of ceruloplasmin in blood. The applied external
      magnetic field was a factor which yielded better sensitivity and repeatability of
      the sensor response. The linearity of sensor response was found to be between
      0.001 and 10MUgdL-1 and 0.05-10MUgdL-1 for both nanoconjugates: Fe@C-Fc-1 and
      Fe@C-Fc-2, in the presence and absence of the magnet, respectively. The obtained
      detection limit (LOD) for Fe@C-Fc-1 was found to be 0.60 and 0.10MUgdL-1 in the
      absence and presence of magnetic field, respectively, whilst for Fe@C-Fc-2 was
      0.4 and 0.07MUgdL-1 in the absence and presence of a magnet, respectively. The
      proposed method is selective because the presence of common antioxidants in blood
      did not interfere significantly with the determination of the concentration of
      ceruloplasmin.

PMID- 29195220
TI  - A comprehensive combined experimental and computational framework for pre
      clinical wear simulation of total knee replacements.
AB  - A more robust pre-clinical wear simulation framework is required in order to
      simulate wider and higher ranges of activities, observed in different patient
      populations such as younger more active patients. Such a framework will help to
      understand and address the reported higher failure rates for younger and more
      active patients (National_Joint_Registry, 2016). The current study has developed
      and validated a comprehensive combined experimental and computational framework
      for pre-clinical wear simulation of total knee replacements (TKR). The input
      mechanical (elastic modulus and Poisson's ratio) and wear parameters of the
      moderately cross-linked ultra-high molecular weight polyethylene (UHMWPE) bearing
      material were independently measured from experimental studies under realistic
      test conditions, similar to the loading conditions found in the total knee
      replacements. The wear predictions from the computational wear simulation were
      validated against the direct experimental wear measurements for size 3 Sigma
      curved total knee replacements (DePuy, UK) in an independent experimental wear
      simulation study under three different daily activities; walking, deep squat, and
      stairs ascending kinematic conditions. The measured compressive mechanical
      properties of the moderately cross-linked UHMWPE material were more than 20%
      lower than that reported in the literature under tensile test conditions. The pin
      on-plate wear coefficient of moderately cross-linked UHMWPE was significantly
      dependant of the contact stress and the degree of cross-shear at the articulating
      surfaces. The computational wear predictions for the TKR from the current
      framework were consistent and in a good agreement with the independent full TKR
      experimental wear simulation measurements, with 0.94 coefficient of determination
      of the framework. In addition, the comprehensive combined experimental and
      computational framework was able to explain the complex experimental wear trends
      from the three different daily activities investigated. Therefore, such a
      framework can be adopted as a pre-clinical simulation approach to optimise
      different designs, materials, as well as patient's specific total knee
      replacements for a range of activities.

PMID- 29195221
TI  - Comparison of ballistic impact effects between biological tissue and gelatin.
AB  - Gelatin is commonly used in ballistic testing as substitute for biological
      tissue. Comparison of ballistic impact effects produced in the gelatin and living
      tissue is lacking. The work in this paper was aimed to compare the typical
      ballistic impact effects (penetration trajectory, energy transfer, temporary
      cavity) caused by 4.8mm steel ball penetrating the 60kg porcine hind limbs and
      10wt% gelatin. The impact event in the biological tissue was recorded by high
      speed flash X-ray machine at different delay time, while the event in the gelatin
      continuously recorded by high speed video was compared to that in the biological
      tissue. The collected results clearly displayed that the ballistic impact effects
      in the muscle and gelatin were similar for the steel ball test; as for instance,
      the projectile trajectory in the two targets was basically similar, the process
      of energy transfer was highly coincident, and the expansion of temporary cavity
      followed the same pattern. This study fully demonstrated that choosing gelatin as
      muscle simulant was reasonable. However, the maximum temporary cavity diameter in
      the gelatin was a little larger than that in the muscle, and the expansion period
      of temporary cavity was longer in the gelatin. Additionally, the temporary cavity
      collapse process in the two targets followed different patterns, and the collapse
      period in the gelatin was two times as long as that in the muscle.

PMID- 29195222
TI  - PAH (Polycyclic Aromatic Hydrocarbon) bioaccumulation and PAHs/shell weight index
      in Ruditapes philippinarum (Adams & Reeve, 1850) from the Vallona lagoon
      (northern Adriatic Sea, NE Italy).
AB  - The Vallona lagoon is a transitional area located in the Po River delta (NE,
      ITALY) traditionally exploited for Manila clam (Ruditapes philippinarum) farming.
      During 2007-2008, a pipeline was buried in the middle of the lagoon to connect an
      off-shore structure to facilities on land. PAH levels were monitored in Manila
      clams and sediments before, during and after the pipeline construction to assess
      the impact of the activities through the pattern of distribution of the PAH
      compounds. PAH bioaccumulation in clams displayed seasonal fluctuations with
      higher levels in autumnal and wintry surveys than in spring-summer. Principal
      component analysis applied to PAHs in clams highlighted a petrogenic input during
      ante operam period and a pyrolytic origin during the burying activities. On the
      contrary, sediment PAH concentrations resulted quite similar both among sites and
      periods. Biota-Sediment-Accumulation-Factor values also confirmed that sediments
      were not the major source of PAH pollution for clams in this study. The welfare
      of clams was examined through two physiological indices (condition index and
      survival in air) to check the effects of the activities on a commercial resource.
      Both physiological indices exhibited seasonal variations connected to natural
      endogenous and exogenous factors; however survival in air was the most sensitive
      index in highlighting the effects of the pipeline burying activities. Finally, to
      ensure that PAH bioavailability assessment was not affected by seasonal variation
      of soft tissues of molluscs, PAHs/shell weight index was applied. Higher levels
      of this index were observed before and during the burying activities, whilst,
      after that, values significantly lowered. Moreover, the normalization enabled us
      to highlight the PAH uptake from clams in some particular periods and to compare
      different populations in a long-term biomonitoring program with data obtained
      from different periods of the year.

PMID- 29195223
TI  - Dissipation behaviour, residue distribution and dietary risk assessment of
      tetraconazole and kresoxim-methyl in greenhouse strawberry via RRLC-QqQ-MS/MS
      technique.
AB  - 20% commercial suspension emulsion (SE) of (8% tetraconazole + 12% kresoxim
      methyl), as a pre-registered product in China, was firstly investigated under
      Chinese greenhouse-field conditions. A MWCNTs-based QuEChERS method for
      simultaneous determination of tetraconazole and kresoxim-methyl in strawberry was
      developed and validated via RRLC-QqQ-MS/MS. On basis of this method, the
      dissipation behaviours, residue distributions and dietary risk probability of
      these fungicides in strawberry were further investigated for food safety. The
      dissipations of tetraconazole and kresoxim-methyl followed first-order kinetics
      with the half-lives of 8.0-18.2 days. The highest residues (HRs) of these
      fungicides in the supervised trials at the pre-harvest interval (PHI, 3 days)
      were below 0.8970mgkg-1. The total national estimated daily intake (NEDI) of
      tetraconazole and kresoxim-methy in strawberry at the PHI 3day was 0.2784mg and
      0.4031mg, respectively, based on Chinese dietary pattern and terminal residue
      distributions under good agricultural practices (GAP) conditions. The risk
      quotients (RQs) of tetraconazole and kresoxim-methy at PHI 3 days were below
      82.7% and 1.6%, respectively, showing that the evaluated strawberry exhibited an
      acceptably low dietary risk to consumers. The current study could not only guide
      reasonable usage of the formulation, but also facilitate the setting of maximum
      residue limits (MRLs) of tetraconazole in strawberry.

PMID- 29195224
TI  - Combined application of compost and Bacillus sp. CIK-512 ameliorated the lead
      toxicity in radish by regulating the homeostasis of antioxidants and lead.
AB  - Lead (Pb) contamination is ubiquitous and usually causes toxicity to plants.
      Nevertheless, application of compost and plant growth promoting rhizobacteria
      synergistically may ameliorate the Pb toxicity in radish. The present study
      assessed the effects of compost and Bacillus sp. CIK-512 on growth, physiology,
      antioxidants and uptake of Pb in contaminated soil and explored the possible
      mechanism for Pb phytotoxicity amelioration. Treatments comprised of un
      inoculated control, compost, CIK-512, and compost + CIK-512; plants were grown in
      soil contaminated with Pb (500mgkg-1) and without Pb in pot culture. Lead caused
      reduction in shoot dry biomass, photosynthetic rate, stomatal conductance,
      relative water contents, whereas enhanced root dry biomass, ascorbate peroxidase,
      catalase, malondialdehyde and electrolyte leakage in comparison with non
      contaminated control. Plants inoculated with strain CIK-512 and compost produced
      significantly higher dry biomass, photosynthetic rate and stomatal conductance in
      normal and contaminated soils. Bacterial strain CIK-512 and compost synergy
      improved growth and physiology of radish in contaminated soil possibly through
      homeostasis of antioxidant activities, reduced membrane leakage and Pb
      accumulation in shoot. Possibly, Pb-induced production of reactive oxygen species
      resulted in increased electrolyte leakage and malondialdehyde contents (r = 0.88
      0.92), which led to reduction in growth (r = -0.97) and physiology (r = -0.38 to 
      0.80), however, such negative effects were ameliorated by the regulation of
      antioxidants (r = 0.78-0.87). The decreased activity of antioxidants coupled with
      Pb accumulation in aerial part of the radish indicates the Pb-phytotoxicity
      amelioration through synergistic application of compost and Bacillus sp. CIK-512.

PMID- 29195225
TI  - Stigma and functional disability in relation to marriage and employment in young
      people with epilepsy in rural Tanzania.
AB  - PURPOSE: To assess the impact of childhood epilepsy on social transitioning
      outcomes for young people with epilepsy (YPWE) living in Tanzania, and to explore
      influences on these outcomes. METHODS: At six years from baseline, we followed up
      84 YPWE and 79 age- sex- and village- matched controls recruited into a case
      control study of childhood epilepsy in rural northern Tanzania. Data were
      collected from interviews with young people and their carers using a structured
      questionnaire. Perceived stigma was evaluated using the Kilifi Stigma Score and
      functional disability using the Barthel Index (BI). The effects of age, gender,
      functional disability and stigma on selected markers of social transitioning
      (education, employment and relationships) were estimated using multivariable
      modelling. RESULTS: Fewer YPWE than controls were in an intimate relationship
      (42.3% vs. 76.9%) or in education or paid employment (33.3% vs. 91.1%) and they
      reported elevated perceived stigma scores (27.4% vs. 3.8%). Among YPWE, a
      positive education or employment outcome was predicted by a lower seizure
      frequency (adjusted OR 3.79) and a higher BI score (adj. OR 12.12); a positive
      relationship outcome was predicted by a higher BI score (adj. OR 45.86) and being
      male (adj. OR 8.55). CONCLUSION: YPWE were more likely to experience adverse
      employment, educational and relationship outcomes in the transition to adult life
      than controls, with the greatest disadvantage experienced by females, those with
      greater functional disability and those with poorer seizure control. Markers of
      social transitioning should be included in any prospective evaluation of
      interventions designed to support these groups.

PMID- 29195226
TI  - The Viral Hypothesis of Mesial Temporal Lobe Epilepsy - Is Human Herpes Virus-6
      the Missing Link? A systematic review and meta-analysis.
AB  - PURPOSE: Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder.
      Although likely multifactorial, the mechanisms underlying the etiology and
      pathogenesis of the disease remains unknown in majority of patients. Viruses,
      particularly Human Herpes Virus 6A and B (HHV-6), two neurotropic herpes viruses,
      have been implicated in MTLE due to their ubiquitous nature and ability to
      establish lifelong latency with risk of reactivation. However, the results of
      studies investigating this relationship are conflicting. This systematic review
      and meta-analysis was conducted to determine the relationship between HHV-6 DNA
      (not specifying if A or B) in brain tissue and MTLE based on the current
      evidence. METHOD: Two independent assessors carried out a comprehensive
      electronic search to identify all relevant studies. Both fixed- and random
      effects models were used to determine the overall odds ratio. RESULTS: A total of
      10 studies met the inclusion criteria for the systematic review and eight for the
      meta-analysis. In 19.6% of all MTLE patients HHV-6 DNA was detected in brain
      tissue compared to 10.3% of all controls (p >0.05). The pooled odds ratio of HHV
      6 positive cases in MTLE patients was 2.016 [95%-CI: 1.16-3.50] in the fixed
      effect model. CONCLUSION: The results of this meta-analysis indicate an
      association between HHV-6 DNA and MTLE surgically resected tissue samples,
      unspecified if A or B or both. However, the casual relationship and possible
      pathological role of HHV-6 in MTLE are yet to be elucidated. This study's results
      provide a basis for future studies continuing the investigation into pathological
      implications of HHV-6.

PMID- 29195227
TI  - Catestatin, vasostatin, cortisol, and visual analog scale scoring for stress
      assessment in healthy dogs.
AB  - The neuroendocrine glycoprotein chromogranin A is a useful biomarker for stress
      in humans. Chromogranin A epitopes catestatin and vasostatin can be measured in
      dogs using radioimmunoassays. The objective of this study was to evaluate
      catestatin and vasostatin as canine stress biomarkers in a clinical setting.
      Blood and saliva were collected from 33 healthy dogs that were familiar with
      sampling procedures and the animal hospital environment (control group) and 30
      healthy dogs that were unacquainted (stress group). During sampling, stress
      behavior was scored by the same observer using visual analog scale (VAS). Plasma
      was analyzed for catestatin and vasostatin, serum for cortisol, and saliva for
      catestatin. Differences between groups were analyzed using two-sample t-tests and
      P<0.05 was considered significant. Stress behavior VAS score in the control group
      was significantly lower than in the stress group during blood (P=0.002) and
      saliva (P=0.0009) sampling. Serum cortisol and saliva catestatin concentrations
      in the stress group were higher than the control group (P=0.003 and P<0.0001,
      respectively). Serum cortisol concentrations were correlated with those of saliva
      (r=0.34, P=0.04) and plasma catestatin (r=0.29, P=0.03). Plasma catestatin and
      vasostatin did not differ significantly between groups. In conclusion,
      concentrations of saliva catestatin, and serum cortisol, and stress behavior VAS
      scores were significantly higher in the stress group. The results indicate that
      saliva catestatin may be useful as a biomarker for acute psychological stress in
      dogs.

PMID- 29195228
TI  - Potential role of wolf (Canis lupus) as passive carrier of European brown hare
      syndrome virus (EBHSV).
AB  - European brown hare syndrome virus (EBHSV) was detected in a faecal swab
      collected from a wolf carcass in Northern Italy. The full-length genome of the
      EBHSV WOLF/17/2016/ITA strain was determined. In the VP60 capsid gene, the wolf
      strain displayed the highest genetic identity (99.2-99.1% nucleotide and 99.6
      99.7% amino acid) with two EBHSV strains recently found in the intestinal content
      of a red fox and in the spleen and liver of a hare in Northern Italy. This
      finding poses interrogatives on the potential role of carnivores as EBHSV passive
      carriers, favoring the introduction and spread of the virus among different hare
      populations.

PMID- 29195229
TI  - Photo-triggered destabilization of nanoscopic vehicles by dihydroindolizine for
      enhanced anticancer drug delivery in cervical carcinoma.
AB  - The efficacy and toxicity of drugs depend not only on their potency but also on
      their ability to reach the target sites in preference to non-target sites. In
      this regards destabilization of delivery vehicles induced by light can be an
      effective strategy for enhancing drug delivery with spatial and temporal control.
      Herein we demonstrate that the photoinduced isomerization from closed
      (hydrophobic) to open isomeric form (hydrophilic) of a novel DHI encapsulated in
      liposome leads to potential light-controlled drug delivery vehicles. We have used
      steady state and picosecond resolved dynamics of a drug 8-anilino-1
      naphthalenesulfonic acid ammonium salt (ANS) incorporated in liposome to monitor
      the efficacy of destabilization of liposome in absence and presence UVA
      irradiation. Steady state and picosecond resolved polarization gated spectroscopy
      including the well-known strategy of solvation dynamics and Forster resonance
      energy transfer; reveal the possible mechanism out of various phenomena involved
      in destabilization of liposome. We have also investigated the therapeutic
      efficacy of doxorubicin (DOX) delivery from liposome to cervical cancer cell line
      HeLa. The FACS, confocal fluorescence microscopic and MTT assay studies reveal an
      enhanced cellular uptake of DOX leading to significant reduction in cell
      viability (~40%) of HeLa followed by photoresponsive destabilization of liposome.
      Our studies successfully demonstrate that these DHI encapsulated liposomes have
      potential application as a smart photosensitive drug delivery system.

PMID- 29195230
TI  - When stem cells meet graphene: Opportunities and challenges in regenerative
      medicine.
AB  - Recent advances in stem cell research and nanotechnology have significantly
      influenced the landscape of tissue engineering and regenerative medicine. Precise
      and reproducible control of the fate of stem cells and their lineage
      specification have, therefore, become more crucial than ever for the success of
      stem cell-based technologies. Extensive research has been geared towards
      developing materials that are capable of mimicking the physiological
      microenvironment of stem cells and at the same time, controlling their eventual
      fate. An interesting example of these materials is two-dimensional graphene and
      its related derivatives. A high specific surface area coupled with superior
      chemical stability, biocompatibility, and flexibility in functionalization render
      graphene-based nanomaterials one of the most exciting platforms for tissue
      engineering and regenerative medicine applications, especially for stem cell
      growth, proliferation, and differentiation. In this review, we discuss the love
      hate relationship between stem cells and graphene-based nanomaterials in tissue
      engineering and regenerative medicine. We first discuss the role and importance
      of stem cells in tissue engineering and regenerative medicine. We then highlight
      the use of nanomaterials for stem cell control, the interaction between stem
      cells and graphene nanomaterials as well as their biocompatibility,
      biodistribution, and biodegradability considerations. We also offer our
      perspectives on the various challenges and opportunities facing the use of
      graphene and its derivatives for stem cell growth and differentiation.

PMID- 29195231
TI  - Early response to salt ions in maize (Zea mays L.).
AB  - Abscisic acid (ABA) regulates leaf growth and transpiration rate of plants
      exposed to salt stress. Despite the known fact that cell dehydration is
      instrumental for the modulation of ABA concentrations when NaCl is high in the
      external environment, it was never tested as to whether sodium (Na) or chlorine
      (Cl) also modulate ABA concentrations. To answer this question, a hydroponic
      study on maize (Zea mays) was established, by exposing plants to 50mM of sodium
      glucosamide or glucosamine chloride. The effect of both ions on ABA was
      investigated in an early stage before (i) the salt ions accumulated to toxic
      tissue concentrations and before (ii) cells dehydrated. This allowed studying
      early responses to Na and Cl separately, well before plants were stressed by
      these ions. Gas chromatography-mass spectrometry analysis was used to quantify
      ABA concentrations in roots and in leaves after a period of 2h after ion
      application. The transcript abundance of the key regulatory enzyme of the
      biosynthesis of ABA in maize, the 9-cis-epoxycarotenoid dioxygenase gene
      viviparous 14, was quantified via real-time quantitative-reverse-transcriptase
      polymerase-chain-reaction. The results reveal that Cl and Na induce the increase
      of leaf tissue ABA concentrations at two hours after plants were exposed to 50mM
      of the ions. Surprisingly, this effect was more pronounced in response to the Cl
      component. The increase in the guard-cell regulating ABA concentration correlated
      with a reduced transpiration. Mainly because of this result we suggest that the
      early accumulation of ABA is useful in maintaining cell turgor.

PMID- 29195232
TI  - Kaolin modulates ABA and IAA dynamics and physiology of grapevine under
      Mediterranean summer stress.
AB  - The foliar exogenous application of kaolin, a radiation-reflecting inert mineral,
      has proven to be an effective short-term climate change mitigation strategy for
      Mediterranean vineyards. In this work, we address the hypothesis that kaolin
      could improve both the hormonal dynamics and physiological responses of
      grapevines growing in Douro Region, northern Portugal. For this purpose, the leaf
      water potential, gas exchange and chlorophyll a fluorescence parameters were
      monitored, as well as the abscisic acid (ABA) and indole-3-acetic acid (IAA)
      quantification and immunolocalization were assessed. The study revealed a slight
      decrease in ABA and an increase in IAA in the kaolin treatment, which in turn
      were associated with the improvement of physiological performance. A month after
      spraying, kaolin improves the water potential respectively, 30% and 17% in the
      predawn and midday periods. Besides, plants treated with kaolin showed higher
      values of stomatal conductance, net CO2 assimilation rate and intrinsic water use
      efficiency. Kaolin also ameliorates the effective PSII efficiency (67%), as well
      as the maximum quantum efficiency of photosystem II and the photosynthetic
      electron transport rate (>73%). These results were consistent with the higher
      photochemical quenching and the lower non-photochemical quenching observed in
      treated leaves and with the better performance obtained by the JIP test
      parameters. Physiological and hormonal analysis confirmed that kaolin effectively
      enhance grapevine summer stress tolerance.

PMID- 29195234
TI  - Aesthetic Management of Upper and Midface Trauma.

PMID- 29195233
TI  - Therapeutic effect of bone marrow mesenchymal stem cells pretreated with
      acetylsalicylic acid on experimental periodontitis in rats.
AB  - Periodontitis is a local inflammatory environment with dysregulation of host
      responses, which results in destruction of periodontal tissues. Mesenchymal stem
      cells (MSCs) have been proven to play important roles in tissue regeneration by
      serving as progenitor cells, but its therapeutic outcomes are yet, evaluated
      variable and unpredictable because of the influence of local inflammation.
      Acetylsalicylic acid (ASA) has been reported to benefit for MSCs in terms of
      inflammation control and tissue regeneration. In this study, we aimed to explore
      the effect of bone marrow mesenchymal stem cells (BMMSCs) pretreated with ASA
      (ASA-BMMSCs) on periodontal bone repair in a ligature and bacteria-induced
      periodontitis model in rats. We show herein that, ASA-BMMSCs treatment reduced
      inflammatory infiltration and alveolar bone loss in periodontitis rats, reflected
      by immunohistochemistry staining of OPG/RANK-L and Micro-CT. Levels of TNF-alpha
      and IL-17 decreased while IL-10 increased after the treatment of ASA-BMMSCs in
      periodontitis rats. In addition, less osteoclasts number was detected in ASA
      BMMSCs treated group. In vitro study showed that ASA facilitated BMMSCs
      proliferation and differentiation, which might explain the reduced bone loss in
      periodontitis. These results together suggest that local application of ASA
      BMMSCs in periodontal lesion sites is capable of improving inflammatory
      microenvironment, promoting alveolar bone regeneration, thus leading to a
      recovery of periodontal homeostasis. Besides, this study also provides us a new
      idea that a combined application of ASA and BMMSCs may be a novel approach for
      periodontitis treatment and periodontal bone regeneration.

PMID- 29195235
TI  - Complications of Midface Fractures.

PMID- 29195236
TI  - Management of Malocclusion after Maxillofacial Trauma.

PMID- 29195237
TI  - Secondary Repair of the Zygoma.

PMID- 29195238
TI  - Complications of Facial Trauma of the Fronto-orbital Region.

PMID- 29195239
TI  - Secondary Treatment of Naso-orbital Ethmoid Injuries.

PMID- 29195240
TI  - Repair of the Malpositioned Lower Lid.

PMID- 29195241
TI  - Secondary Repair of Posttraumatic Enophthalmos and Extraocular Movement
      Disorders.

PMID- 29195242
TI  - The Role of Hair Transplantation for Managing Facial Trauma.

PMID- 29195243
TI  - Scar Revision: Surgical and Nonsurgical Options.

PMID- 29195244
TI  - Options in Repositioning the Asymmetric Brow from Paralysis and Trauma.

PMID- 29195245
TI  - Prophylactic Measures to Prevent Soft Tissue Abnormalities after Trauma.

PMID- 29195246
TI  - Role of Camouflage in Management of Facial Trauma Deformities.

PMID- 29195247
TI  - Modern Approaches to Skin Care.

PMID- 29195248
TI  - Comparison of Absorbable and Nonabsorbable Sutures in Columellar Incision Closure
      in Rhinoplasty and Their Effects to Postoperative Scar.

PMID- 29195249
TI  - Search Engine Optimization: An Analysis of Rhinoplasty Web sites.

PMID- 29195250
TI  - Optimal Costal Cartilage Graft Selection According to Cartilage Shape: Anatomical
      Considerations for Rhinoplasty.

PMID- 29195251
TI  - Broken-Line Template for Revision of Facial Scars.

PMID- 29195253
TI  - Erratum: Oblique Turnover Flap for Repositioning and Flattening of the Lateral
      Crura: A Novel Technique to Manage Cephalic Malposition of Lower Lateral
      Cartilage.

PMID- 29195254
TI  - On Patience.

PMID- 29195255
TI  - The Right Heart: Ignored and Almost Forgotten.

PMID- 29195256
TI  - Increased postprandial glucagon-like peptide-1 (GLP-1) production after
      endoscopic gastrointestinal bypass using the Cousin lumen-apposing stent in a
      porcine model.
AB  - : BACKGROUND AND STUDY AIMS : Endoscopic techniques have demonstrated their
      effectiveness in metabolic surgery, notably through a gastrointestinal (GI)
      liner, with a less invasive approach than conventional surgery. Our study
      evaluates the safety and efficacy of endoscopic GI anastomosis (EGIA) using a
      lumen-apposing stent to secure the anastomosis. MATERIALS AND METHODS : EGIA was
      performed using the transgastric approach with a two-channel endoscope with a
      novel stent (Cousin Biotech). First, a safety study with a follow-up of 12 months
      was performed on five piglets. Then, metabolic changes were investigated in a
      minipig model (n = 10) before and after EGIA or open GIA (OGIA). RESULTS: EGIA
      was technically successful with no complications observed during clinical
      monitoring. Endoscopic and postmortem examinations during the second part of
      study showed a secure anastomosis between the stomach and the intestinal limb in
      all except one minipig. Both minipigs subjected to EGIA and those in the control
      group (OGIA) exhibited increased postprandial glucagon-like peptide-1 (GLP-1)
      production (incretin secretion) and impaired D-xylose absorption (malabsorption
      effect). CONCLUSION : Performing EGIA with this dedicated stent appears safe,
      technically feasible, durable, and reproducible in providing a simple and
      effective endoscopic GI bypass capable of ensuring metabolic effect.

PMID- 29195257
TI  - [Editor's Comment].

PMID- 29195258
TI  - ?

PMID- 29195259
TI  - ?

PMID- 29195260
TI  - ?

PMID- 29195261
TI  - ?

PMID- 29195262
TI  - [Biosimilars and the efficiency principle].
AB  - Biosimilars are subject to the efficiency evaluation according to section 106
      Social Code Book Five (SGB V). The specific evaluation method influences the
      physician's prescription behaviour. In the case of an individual prescription
      limit evaluation (Richtgrobetaenprufung), the prescription of biosimilars would
      usually not result in recourse but, as a start, in the initiation of the
      evaluation proceedings. Starting from 2017, the individual prescription limit
      evaluation will be cancelled. The active ingredient evaluation (Wirkstoffprufung)
      expected instead at a regional level may provide for biosimilar to original drug
      ratios and result in recourses if these ratios are missed. First agreements on
      specific evaluation proceedings at a regional level are expected for this year.

PMID- 29195263
TI  - ?

PMID- 29195264
TI  - ?

PMID- 29195265
TI  - ?

PMID- 29195266
TI  - ?

PMID- 29195267
TI  - Do Brazilian Pregnant Women Need Iodine Supplementation? A Commentary on the
      Latest American Thyroid Association Guideline.

PMID- 29195268
TI  - Endoscopic and Microscopic Transsphenoidal Surgery of Craniopharyngiomas: A
      Systematic Review of Surgical Outcomes Over Two Decades.
AB  - OBJECTIVE:  Few studies have compared transsphenoidal endoscopic (TE) and
      transsphenoidal microscopic (TM) techniques for the treatment of
      craniopharyngiomas. DESIGN:  We performed a systematic review of published
      series. The results were stratified in two time periods from 1995 to 2016.
      RESULTS:  A total of 48 articles and 1,186 patients met the inclusion criteria.
      Overall, 60% of endoscopic cases were supradiaphragmatic, and 76% of
      microsurgical cases were infradiaphragmatic. Mean tumor size was 3 cm and 2.4 cm
      in the TE and TM series, respectively (p = 0.008). Total resection rate was
      similar (66%) between TE and TM. Considering the surgical outcome for different
      tumor locations, total resection rate was slightly higher in the TE for
      supradiaphragmatic lesions (59% versus 42.5%; p = 0.26). Recurrence rate was
      higher in the endoscopic series (21.7% versus 12%). Mortality and the overall
      complication rates were similar (p = 0.84). However, hydrocephalus (7.6%) and
      cognitive dysfunction (15.8%) were more common in TE, and meningitis (6%) and
      endocrinologic complications were more common in the TM series. In the past 6
      years, the rate of cerebrospinal fluid leak in TE was significantly lower (13%)
      and was comparable between TE and TM. CONCLUSION:  Both techniques appear
      comparable for infradiaphragmatic lesions; however, TE seems to yield better
      results for supradiaphragmatic tumors. In conclusion, more complex lesions with
      difficult locations can be effectively treated with endoscopic surgery.

PMID- 29195269
TI  - [The revised version of standard terminology in gastroenterological endoscopy -
      result of a consensus project of the german society for gastroenterology,
      digestive and metabolic diseases].

PMID- 29195270
TI  - Compositional Proteomics: Effects of Spatial Constraints on Protein
      Quantification Utilizing Isobaric Tags.
AB  - Mass spectrometry (MS) has become an accessible tool for whole proteome
      quantitation with the ability to characterize protein expression across thousands
      of proteins within a single experiment. A subset of MS quantification methods
      (e.g., SILAC and label-free) monitor the relative intensity of intact peptides,
      where thousands of measurements can be made from a single mass spectrum. An
      alternative approach, isobaric labeling, enables precise quantification of
      multiple samples simultaneously through unique and sample specific mass reporter
      ions. Consequently, in a single scan, the quantitative signal comes from a
      limited number of spectral features (<=11). The signal observed for these
      features is constrained by automatic gain control, forcing codependence of
      concurrent signals. The study of constrained outcomes primarily belongs to the
      field of compositional data analysis. We show experimentally that isobaric tag
      proteomics data are inherently compositional and highlight the implications for
      data analysis and interpretation. We present a new statistical model and
      accompanying software that improves estimation accuracy and the ability to detect
      changes in protein abundance. Finally, we demonstrate a unique compositional
      effect on proteins with infinite changes. We conclude that many infinite changes
      will appear small and that the magnitude of these estimates is highly dependent
      on experimental design.

PMID- 29195271
TI  - Distinctive Three-Step Hysteretic Sorption of Ethane with In Situ
      Crystallographic Visualization of the Pore Forms in a Soft Porous Crystal.
AB  - A soft porous Zn(II)-MOF (1) displays distinctive three-step hysteretic breathing
      behavior under ethane gas pressure at ambient temperatures. In situ single
      crystal X-ray diffraction analysis was carried out at 298 K using an
      environmental gas cell in order to elucidate the different porous forms of the
      breathing framework under ethane gas. The three different phases were further
      characterized by pressure-gradient differential scanning calorimetry and variable
      pressure powder X-ray diffraction analysis.

PMID- 29195272
TI  - Multivalent Antimicrobial Polymer Nanoparticles Target Mycobacteria and Gram
      Negative Bacteria by Distinct Mechanisms.
AB  - Because of the emergence of antimicrobial resistance to traditional small
      molecule drugs, cationic antimicrobial polymers are appealing targets.
      Mycobacterium tuberculosis is a particular problem, with multi- and total drug
      resistance spreading and more than a billion latent infections globally. This
      study reports nanoparticles bearing variable densities of poly(dimethylaminoethyl
      methacrylate) and the unexpected and distinct mechanisms of action this
      multivalent presentation imparts against Escherichia coli versus Mycobacterium
      smegmatis (model of M. tuberculosis), leading to killing or growth inhibition,
      respectively. A convergent "grafting to" synthetic strategy was used to assemble
      a 50-member nanoparticle library, and using a high-throughput screen identified
      that only the smallest (2 nm) particles were stable in both saline and complex
      cell media. Compared with the linear polymers, the nanoparticles displayed two-
      and eight-fold enhancements in antimicrobial activity against M. smegmatis and E.
      coli, respectively. Mechanistic studies demonstrated that the antimicrobial
      particles were bactericidal against E. coli due to rapid disruption of the cell
      membranes. Conversely, against M. smegmatis the particles did not lyse the cell
      membrane but rather had a bacteriostatic effect. These results demonstrate that
      to develop new polymeric antituberculars the widely assumed, broad spectrum,
      membrane-disrupting mechanism of polycations must be re-evaluated. It is clear
      that synthetic nanomaterials can engage in more complex interactions with
      mycobacteria, which we hypothesize is due to the unique cell envelope at the
      surface of these bacteria.

PMID- 29195273
TI  - Proteoform Suite: Software for Constructing, Quantifying, and Visualizing
      Proteoform Families.
AB  - We present an open-source, interactive program named Proteoform Suite that uses
      proteoform mass and intensity measurements from complex biological samples to
      identify and quantify proteoforms. It constructs families of proteoforms derived
      from the same gene, assesses proteoform function using gene ontology (GO)
      analysis, and enables visualization of quantified proteoform families and their
      changes. It is applied here to reveal systemic proteoform variations in the yeast
      response to salt stress.

PMID- 29195274
TI  - Self-Assembly of Telechelic Tyrosine End-Capped PEO Star Polymers in Aqueous
      Solution.
AB  - We investigate the self-assembly of two telechelic star polymer-peptide
      conjugates based on poly(ethylene oxide) (PEO) four-arm star polymers capped with
      oligotyrosine. The conjugates were prepared via N-carboxy anhydride-mediated ring
      opening polymerization from PEO star polymer macroinitiators. Self-assembly
      occurs above a critical aggregation concentration determined via fluorescence
      probe assays. Peptide conformation was examined using circular dichroism
      spectroscopy. The structure of self-assembled aggregates was probed using small
      angle X-ray scattering and cryogenic transmission electron microscopy. In
      contrast to previous studies on linear telechelic PEO-oligotyrosine conjugates
      that show self-assembly into beta-sheet fibrils, the star architecture suppresses
      fibril formation and micelles are generally observed instead, a small population
      of fibrils only being observed upon pH adjustment. Hydrogelation is also
      suppressed by the polymer star architecture. These peptide-functionalized star
      polymer solutions are cytocompatible at sufficiently low concentration. These
      systems present tyrosine at high density and may be useful in the development of
      future enzyme or pH-responsive biomaterials.

PMID- 29195276
TI  - Short-range second order screened exchange correction to RPA correlation
      energies.
AB  - Direct random phase approximation (RPA) correlation energies have become
      increasingly popular as a post-Kohn-Sham correction, due to significant
      improvements over DFT calculations for properties such as long-range dispersion
      effects, which are problematic in conventional density functional theory. On the
      other hand, RPA still has various weaknesses, such as unsatisfactory results for
      non-isogyric processes. This can in parts be attributed to the self-correlation
      present in RPA correlation energies, leading to significant self-interaction
      errors. Therefore a variety of schemes have been devised to include exchange in
      the calculation of RPA correlation energies in order to correct this shortcoming.
      One of the most popular RPA plus exchange schemes is the second order screened
      exchange (SOSEX) correction. RPA + SOSEX delivers more accurate absolute
      correlation energies and also improves upon RPA for non-isogyric processes. On
      the other hand, RPA + SOSEX barrier heights are worse than those obtained from
      plain RPA calculations. To combine the benefits of RPA correlation energies and
      the SOSEX correction, we introduce a short-range RPA + SOSEX correction. Proof of
      concept calculations and benchmarks showing the advantages of our method are
      presented.

PMID- 29195277
TI  - Sub-500 fs electronically nonadiabatic chemical dynamics of energetic molecules
      from the S1 excited state: Ab initio multiple spawning study.
AB  - Energetic materials store a large amount of chemical energy. Different ignition
      processes, including laser ignition and shock or compression wave, initiate the
      energy release process by first promoting energetic molecules to the
      electronically excited states. This is why a full understanding of initial steps
      of the chemical dynamics of energetic molecules from the excited electronic
      states is highly desirable. In general, conical intersection (CI), which is the
      crossing point of multidimensional electronic potential energy surfaces, is well
      established as a controlling factor in the initial steps of chemical dynamics of
      energetic molecules following their electronic excitations. In this article, we
      have presented different aspects of the ultrafast unimolecular relaxation
      dynamics of energetic molecules through CIs. For this task, we have employed ab
      initio multiple spawning (AIMS) simulation using the complete active space self
      consistent field (CASSCF) electronic wavefunction and frozen Gaussian-based
      nuclear wavefunction. The AIMS simulation results collectively reveal that the
      ultrafast relaxation step of the best energetic molecules (which are known to
      exhibit very good detonation properties) is completed in less than 500 fs. Many,
      however, exhibit sub-50 fs dynamics. For example, nitro-containing molecules
      (including C-NO2, N-NO2, and O-NO2 active moieties) relax back to the ground
      state in approximately 40 fs through similar (S1/S0)CI conical intersections. The
      N3-based energetic molecule undergoes the N2 elimination process in 40 fs through
      the (S1/S0)CI conical intersection. Nitramine-Fe complexes exhibit sub-50 fs Fe-O
      and N-O bond dissociation through the respective (S1/S0)CI conical intersection.
      On the other hand, tetrazine-N-oxides, which are known to exhibit better
      detonation properties than tetrazines, undergo internal conversion in a 400-fs
      time scale, while the relaxation time of tetrazine is very long (about 100 ns).
      Many other characteristics of sub-500 fs nonadiabatic decay of energetic
      molecules are discussed. In the end, many unresolved issues associated with the
      ultrafast nonadiabatic chemical dynamics of energetic molecules are presented.

PMID- 29195278
TI  - Localization switching of a large object in a crowded cavity: A rigid/soft object
      prefers surface/inner positioning.
AB  - For living cells in the real world, a large organelle is commonly positioned in
      the inner region away from membranes, such as the nucleus of eukaryotic cells,
      the nucleolus of nuclei, mitochondria, chloroplast, Golgi body, etc. It
      contradicts the expectation by the current depletion-force theory in that the
      larger particle should be excluded from the inner cell space onto cell boundaries
      in a crowding media. Here we simply model a sizable organelle as a soft-boundary
      large particle allowing crowders, which are smaller hard spheres in the model, to
      intrude across its boundary. The results of Monte Carlo simulation indicate that
      the preferential location of the larger particle switches from the periphery into
      the inner region of the cavity by increasing its softness. An integral equation
      theory is further developed to account for the structural features of the model,
      and the theoretical predictions are found consistent with our simulation results.

PMID- 29195279
TI  - Measurement of the Na2 51Sigmag+->A1Sigmau+ and 61Sigmag+->A1Sigmau+ transition
      dipole moments using optical-optical double resonance and Autler-Townes
      spectroscopy.
AB  - Accurate knowledge of transition dipole moment matrix elements is crucial since
      important parameters associated with the interaction of light with matter, such
      as emission and absorption line intensities, lifetimes, and Einstein
      coefficients, depend on these matrix elements. We report here an experimental
      study of the Na2 51Sigmag+<->A1Sigmau+ and 61Sigmag+<->A1Sigmau+ electronic
      transition dipole moments and their dependence on internuclear distance. We have
      measured absolute transition dipole matrix elements for ro-vibrational
      transitions of the Na2 51Sigmag+<->A1Sigmau+ and 61Sigmag+<->A1Sigmau+ electronic
      transitions using Autler-Townes and optical-optical double resonance
      spectroscopy, and we compare the results to ab initio theoretical values [A.
      Sanli et al., J. Chem. Phys. 143, 104304 (2015)].

PMID- 29195275
TI  - Functional Modification of Silica through Enhanced Adsorption of Elastin-Like
      Polypeptide Block Copolymers.
AB  - A powerful tool for controlling interfacial properties and molecular architecture
      relies on the tailored adsorption of stimuli-responsive block copolymers onto
      surfaces. Here, we use computational and experimental approaches to investigate
      the adsorption behavior of thermally responsive polypeptide block copolymers
      (elastin-like polypeptides, ELPs) onto silica surfaces, and to explore the
      effects of surface affinity and micellization on the adsorption kinetics and the
      resultant polypeptide layers. We demonstrate that genetic incorporation of a
      silica-binding peptide (silaffin R5) results in enhanced adsorption of these
      block copolymers onto silica surfaces as measured by quartz crystal microbalance
      and ellipsometry. We find that the silaffin peptide can also direct micelle
      adsorption, leading to close-packed micellar arrangements that are distinct from
      the sparse, patchy arrangements observed for ELP micelles lacking a silaffin tag,
      as evidenced by atomic force microscopy measurements. These experimental findings
      are consistent with results of dissipative particle dynamics simulations.
      Wettability measurements suggest that surface immobilization hampers the
      temperature-dependent conformational change of ELP micelles, while adsorbed ELP
      unimers (i.e., unmicellized block copolymers) retain their thermally responsive
      property at interfaces. These observations provide guidance on the use of ELP
      block copolymers as building blocks for fabricating smart surfaces and interfaces
      with programmable architecture and functionality.

PMID- 29195280
TI  - Anomalous phase behavior of first-order fluid-liquid phase transition in
      phosphorus.
AB  - Although the existence of liquid-liquid phase transition has become more and more
      convincing, whether it will terminate at a critical point and what is the order
      parameter are still open. To explore these questions, we revisit the fluid-liquid
      phase transition (FLPT) in phosphorus (P) and study its phase behavior by
      performing extensive first-principles molecular dynamics simulations. The FLPT
      observed in experiments is well reproduced, and a fluid-liquid critical point
      (FLCP) at T = 3000 ~ 3500 K, P = 1.5-2.0 Kbar is found. With decreasing
      temperature from the FLCP along the transition line, the density difference
      (Deltarho) between two coexisting phases first increases from zero and then
      anomalously decreases; however, the entropy difference (DeltaS) continuously
      increases from zero. These features suggest that an order parameter containing
      contributions from both the density and the entropy is needed to describe the
      FLPT in P, and at least at low temperatures, the entropy, instead of the density,
      governs the FLPT.

PMID- 29195281
TI  - Thermodynamic framework for information in nanoscale systems with memory.
AB  - Information is represented by linear strings of symbols with memory that carry
      errors as a result of their stochastic nature. Proofreading and edition are
      assumed to improve certainty although such processes may not be effective. Here,
      we develop a thermodynamic theory for material chains made up of nanoscopic
      subunits with symbolic meaning in the presence of memory. This framework is based
      on the characterization of single sequences of symbols constructed under a
      protocol and is used to derive the behavior of ensembles of sequences similarly
      constructed. We then analyze the role of proofreading and edition in the presence
      of memory finding conditions to make revision an effective process, namely, to
      decrease the entropy of the chain. Finally, we apply our formalism to DNA
      replication and RNA transcription finding that Watson and Crick hybridization
      energies with which nucleotides are branched to the template strand during the
      copying process are optimal to regulate the fidelity in proofreading. These
      results are important in applications of information theory to a variety of solid
      state physical systems and other biomolecular processes.

PMID- 29195282
TI  - Virial coefficients of anisotropic hard solids of revolution: The detailed
      influence of the particle geometry.
AB  - We provide analytical expressions for the second virial coefficients of
      differently shaped hard solids of revolution in dependence on their aspect ratio.
      The second virial coefficients of convex hard solids, which are the orientational
      averages of the mutual excluded volume, are derived from volume, surface, and
      mean radii of curvature employing the Isihara-Hadwiger theorem. Virial
      coefficients of both prolate and oblate hard solids of revolution are
      investigated in dependence on their aspect ratio. The influence of one- and two
      dimensional removable singularities of the surface curvature to the mutual
      excluded volume is analyzed. The virial coefficients of infinitely thin oblate
      and infinitely long prolate particles are compared, and analytical expressions
      for their ratios are derived. Beyond their dependence on the aspect ratio, the
      second virial coefficients are influenced by the detailed geometry of the
      particles.

PMID- 29195283
TI  - Multiple-trapping model of dielectric relaxation of the ice Ih.
AB  - A microscopic theory of dielectric relaxation of the hexagonal ice (Ih) is
      proposed based on the multiple-trapping model. The theory explains the
      distinctive peculiarities of the relaxation time temperature behavior and the
      peak broadening parameter in a wide temperature range from the unified positions.

PMID- 29195284
TI  - Dynamic principle for ensemble control tools.
AB  - Dynamical equations describing physical systems in contact with a thermal bath
      are commonly extended by mathematical tools called "thermostats." These tools are
      designed for sampling ensembles in statistical mechanics. Here we propose a
      dynamic principle underlying a range of thermostats which is derived using
      fundamental laws of statistical physics and ensures invariance of the canonical
      measure. The principle covers both stochastic and deterministic thermostat
      schemes. Our method has a clear advantage over a range of proposed and widely
      used thermostat schemes that are based on formal mathematical reasoning.
      Following the derivation of the proposed principle, we show its generality and
      illustrate its applications including design of temperature control tools that
      differ from the Nose-Hoover-Langevin scheme.

PMID- 29195285
TI  - Communication: Diverse nanoscale cluster dynamics: Diffusion of 2D epitaxial
      clusters.
AB  - The dynamics of nanoscale clusters can be distinct from macroscale behavior
      described by continuum formalisms. For diffusion of 2D clusters of N atoms in
      homoepitaxial systems mediated by edge atom hopping, macroscale theory predicts
      simple monotonic size scaling of the diffusion coefficient, DN ~ N-beta, with
      beta = 3/2. However, modeling for nanoclusters on metal(100) surfaces reveals
      that slow nucleation-mediated diffusion displaying weak size scaling beta < 1
      occurs for "perfect" sizes Np = L2 and L(L+1) for integer L = 3,4,... (with
      unique square or near-square ground state shapes), and also for Np+3, Np+4,....
      In contrast, fast facile nucleation-free diffusion displaying strong size scaling
      beta ~ 2.5 occurs for sizes Np+1 and Np+2. DN versus N oscillates strongly
      between the slowest branch (for Np+3) and the fastest branch (for Np+1). All
      branches merge for N = O(102), but macroscale behavior is only achieved for much
      larger N = O(103). This analysis reveals the unprecedented diversity of behavior
      on the nanoscale.

PMID- 29195286
TI  - Combining extrapolation with ghost interaction correction in range-separated
      ensemble density functional theory for excited states.
AB  - The extrapolation technique of Savin [J. Chem. Phys. 140, 18A509 (2014)], which
      was initially applied to range-separated ground-state-density-functional
      Hamiltonians, is adapted in this work to ghost-interaction-corrected (GIC) range
      separated ensemble density-functional theory (eDFT) for excited states. While
      standard extrapolations rely on energies that decay as MU-2 in the large range
      separation-parameter MU limit, we show analytically that (approximate) range
      separated GIC ensemble energies converge more rapidly (as MU-3) towards their
      pure wavefunction theory values (MU -> +infinity limit), thus requiring a
      different extrapolation correction. The purpose of such a correction is to
      further improve on the convergence and, consequently, to obtain more accurate
      excitation energies for a finite (and, in practice, relatively small) MU value.
      As a proof of concept, we apply the extrapolation method to He and small
      molecular systems (viz., H2, HeH+, and LiH), thus considering different types of
      excitations such as Rydberg, charge transfer, and double excitations. Potential
      energy profiles of the first three and four singlet Sigma+ excitation energies in
      HeH+ and H2, respectively, are studied with a particular focus on avoided
      crossings for the latter. Finally, the extraction of individual state energies
      from the ensemble energy is discussed in the context of range-separated eDFT, as
      a perspective.

PMID- 29195287
TI  - A note on the accuracy of KS-DFT densities.
AB  - The accuracy of the density of wave function methods and Kohn-Sham (KS) density
      functionals is studied using moments of the density, ?rn?=? rho
      rrndtau=?0infinity4pir2rho(r)rndr,where n=-1,-2,0,1,2,and 3 provides information
      about the short- and long-range behavior of the density. Coupled cluster (CC)
      singles, doubles, and perturbative triples (CCSD(T)) is considered as the
      reference density. Three test sets are considered: boron through neon neutral
      atoms, two and four electron cations, and 3d transition metals. The total density
      and valence only density are distinguished by dropping appropriate core orbitals.
      Among density functionals tested, CAMQTP00 and omegaB97x show the least deviation
      for boron through neon neutral atoms. They also show accurate eigenvalues for the
      HOMO indicating that they should have a more correct long-range behavior for the
      density. For transition metals, some density functional approximations outperform
      some wave function methods, suggesting that the KS determinant could be a better
      starting point for some kinds of correlated calculations. By using generalized
      many-body perturbation theory (MBPT), the convergence of second-, third-, and
      fourth-order KS-MBPT for the density is addressed as it converges to the infinite
      order coupled cluster result. For the transition metal test set, the deviations
      in the KS density functional theory methods depend on the amount of exact
      exchange the functional uses. Functionals with exact exchange close to 25% show
      smaller deviations from the CCSD(T) density.

PMID- 29195288
TI  - Nucleation mechanism of clathrate hydrates of water-soluble guest molecules.
AB  - The mechanism of nucleation of clathrate hydrates of a water-soluble guest
      molecule is rigorously investigated with molecular dynamics (MD) simulations.
      Results from forward flux sampling, committor probability analysis, and twenty
      straightforward MD trajectories were combined to create a comprehensive
      understanding of the nucleation mechanism. Seven different classes of order
      parameters with a total of 33 individual variants were studied. We rank and
      evaluate the efficacy of prospective reaction coordinate models built from these
      order parameters and linear combinations thereof. Order parameters based upon
      water structuring provide a better approximation of the reaction coordinate than
      those based upon guest structuring. Our calculations suggest that the transition
      state is characterized by 2-3 partial, face-sharing 512 cages that form a
      structural motif observed in the structure II crystal. Further simulations show
      that once formed, this structure significantly affects the ordering of vicinal
      guest molecules, likely leading to hydrate nucleation. Our results contribute to
      the current understanding of the water-guest interplay involved in hydrate
      nucleation and have relevance to hydrate-based technologies that use water
      soluble guest molecules (e.g., tetrahydrofuran) in mixed hydrate systems.

PMID- 29195289
TI  - A variational conformational dynamics approach to the selection of collective
      variables in metadynamics.
AB  - In this paper, we combine two powerful computational techniques, well-tempered
      metadynamics and time-lagged independent component analysis. The aim is to
      develop a new tool for studying rare events and exploring complex free energy
      landscapes. Metadynamics is a well-established and widely used enhanced sampling
      method whose efficiency depends on an appropriate choice of collective variables.
      Often the initial choice is not optimal leading to slow convergence. However by
      analyzing the dynamics generated in one such run with a time-lagged independent
      component analysis and the techniques recently developed in the area of
      conformational dynamics, we obtain much more efficient collective variables that
      are also better capable of illuminating the physics of the system. We demonstrate
      the power of this approach in two paradigmatic examples.

PMID- 29195290
TI  - Static field-gradient polarizabilities of small atoms and molecules at finite
      temperature.
AB  - In this work, we propose new field-free estimators of static field-gradient
      polarizabilities for finite temperature path-integral Monte Carlo method. Namely,
      dipole-quadrupole polarizability A, dipole-dipole-quadrupole polarizability B,
      and quadrupole-quadrupole polarizability C are computed for several up to two
      electron systems: H, H-, He, Li+, Be2+, Ps2, PsH, H2+, H2, H3+, and HeH+. We
      provide complementary data for ground state electronic properties within the
      adiabatic approximation and demonstrate good agreement with available values in
      the literature. More importantly, we present fully non-adiabatic results from 50
      K to 1600 K, which allow us to analyze and discuss strong thermal coupling and
      rovibrational effects in total field-gradient polarizabilities. These phenomena
      are most relevant but clearly overlooked, e.g., in the construction of modern
      polarizable force field models. However, our main purpose is demonstrating the
      accuracy and simplicity of our approach in a problem that is generally
      challenging.

PMID- 29195291
TI  - Communication: Coordinate-dependent diffusivity from single molecule
      trajectories.
AB  - Single-molecule observations of biomolecular folding are commonly interpreted
      using the model of one-dimensional diffusion along a reaction coordinate, with a
      coordinate-independent diffusion coefficient. Recent analysis, however, suggests
      that more general models are required to account for single-molecule measurements
      performed with high temporal resolution. Here, we consider one such
      generalization: a model where the diffusion coefficient can be an arbitrary
      function of the reaction coordinate. Assuming Brownian dynamics along this
      coordinate, we derive an exact expression for the coordinate-dependent
      diffusivity in terms of the splitting probability within an arbitrarily chosen
      interval and the mean transition path time between the interval boundaries. This
      formula can be used to estimate the effective diffusion coefficient along a
      reaction coordinate directly from single-molecule trajectories.

PMID- 29195292
TI  - Water liquid-vapor interface subjected to various electric fields: A molecular
      dynamics study.
AB  - Investigation of the effects of E-fields on the liquid-vapor interface is
      essential for the study of floating water bridge and wetting phenomena. The
      present study employs the molecular dynamics method to investigate the effects of
      parallel and perpendicular E-fields on the water liquid-vapor interface. For this
      purpose, density distribution, number of hydrogen bonds, molecular orientation,
      and surface tension are examined to gain a better understanding of the interface
      structure. Results indicate enhancements in parallel E-field decrease the
      interface width and number of hydrogen bonds, while the opposite holds true in
      the case of perpendicular E-fields. Moreover, perpendicular fields disturb the
      water structure at the interface. Given that water molecules tend to be parallel
      to the interface plane, it is observed that perpendicular E-fields fail to
      realign water molecules in the field direction while the parallel ones easily do
      so. It is also shown that surface tension rises with increasing strength of
      parallel E-fields, while it reduces in the case of perpendicular E-fields.
      Enhancement of surface tension in the parallel field direction demonstrates how
      the floating water bridge forms between the beakers. Finally, it is found that
      application of external E-fields to the liquid-vapor interface does not lead to
      uniform changes in surface tension and that the liquid-vapor interfacial tension
      term in Young's equation should be calculated near the triple-line of the
      droplet. This is attributed to the multi-directional nature of the droplet
      surface, indicating that no constant value can be assigned to a droplet's surface
      tension in the presence of large electric fields.

PMID- 29195293
TI  - Erratum: "Accurate potential energy, dipole moment curves, and lifetimes of
      vibrational states of heteronuclear alkali dimers" [J. Chem. Phys. 140, 184315
      (2014)].

PMID- 29195294
TI  - Correlation effects beyond coupled cluster singles and doubles approximation
      through Fock matrix dressing.
AB  - We present an accurate single reference coupled cluster theory in which the
      conventional Fock operator matrix is suitably dressed to simulate the effect of
      triple and higher excitations within a singles and doubles framework. The
      dressing thus invoked originates from a second-order perturbative approximation
      of a similarity transformed Hamiltonian and induces higher rank excitations
      through local renormalization of individual occupied and unoccupied orbital
      lines. Such a dressing is able to recover a significant amount of correlation
      effects beyond singles and doubles approximation, but only with an economic n5
      additional cost. Due to the inclusion of higher rank excitations via the Fock
      matrix dressing, this method is a natural improvement over conventional coupled
      cluster theory with singles and doubles approximation, and this method would be
      demonstrated via applications on some challenging systems. This highly promising
      scheme has a conceptually simple structure which is also easily generalizable to
      a multi-reference coupled cluster scheme for treating strong degeneracy. We shall
      demonstrate that this method is a natural lowest order perturbative approximation
      to the recently developed iterative n-body excitation inclusive coupled cluster
      singles and doubles scheme [R. Maitra et al., J. Chem. Phys. 147, 074103 (2017)].

PMID- 29195295
TI  - Methods to locate saddle points in complex landscapes.
AB  - We present a class of simple algorithms that allows us to find the reaction path
      in systems with a complex potential energy landscape. The approach does not need
      any knowledge on the product state and does not require the calculation of any
      second derivatives. The underlying idea is to use two nearby points in the
      configuration space to locate the path of the slowest ascent. By introducing a
      weak noise term, the algorithm is able to find even low-lying saddle points that
      are not directly reachable by means of the slowest ascent path. Since the
      algorithm only makes use of the value of the potential and its gradient, the
      computational effort to find saddle points is linear in the number of degrees of
      freedom if the potential is short-ranged. We test the performance of the
      algorithm for three potential energy landscapes. For the Muller-Brown surface, we
      find that the algorithm always finds the correct saddle point. For the modified
      Muller-Brown surface, which has a saddle point that is not reachable by means of
      the slowest ascent path, the algorithm is still able to find this saddle point
      with high probability. For the case of a three-dimensional Lennard-Jones cluster,
      the algorithm is able to find the lowest energy barrier with high probability,
      showing that the method is also efficient in landscapes with many dimensions.

PMID- 29195296
TI  - Time delay in XUV/IR photoionization of H2O.
AB  - We solve the time-dependent Schrodinger equation describing a water molecule
      driven by a superposition of the extreme ultraviolet and IR pulses typical for a
      reconstruction of attosecond beating by interference of two-photon transitions
      experiment. This solution is obtained by a combination of the time-dependent
      coordinate scaling and the density functional theory with self-interaction
      correction. Results of this solution are used to determine the time delay in
      photoionization of the water and hydrogen molecules.

PMID- 29195297
TI  - Random number generator based on an integrated laser with on-chip optical
      feedback.
AB  - We discuss the design and testing of a laser integrated with a long on-chip
      optical feedback section. The device and feedback section have been fabricated on
      a generic photonic integration platform using only standard building blocks. We
      have been able to integrate a 10 cm feedback length on a footprint of 5.5 mm2. By
      controlling the amount of feedback, we achieve chaotic dynamics in the long
      cavity regime and show that the resulting dynamics is sufficiently complex in
      order to generate random bits based on the chaotic intensity fluctuation at a
      rate of 500 Mbits/s.

PMID- 29195298
TI  - New type of chimera and mutual synchronization of spatiotemporal structures in
      two coupled ensembles of nonlocally interacting chaotic maps.
AB  - We study numerically the dynamics of a network made of two coupled one
      dimensional ensembles of discrete-time systems. The first ensemble is represented
      by a ring of nonlocally coupled Henon maps and the second one by a ring of
      nonlocally coupled Lozi maps. We find that the network of coupled ensembles can
      realize all the spatio-temporal structures which are observed both in the Henon
      map ensemble and in the Lozi map ensemble while uncoupled. Moreover, we reveal a
      new type of spatiotemporal structure, a solitary state chimera, in the considered
      network. We also establish and describe the effect of mutual synchronization of
      various complex spatiotemporal patterns in the system of two coupled ensembles of
      Henon and Lozi maps.

PMID- 29195299
TI  - Noise activated bistable sensor based on chaotic system with output defined by
      temporal coding and firing rate.
AB  - Traditional bistable sensors use external bias signal to drive its response
      between states and their detection strategy is based on the output power spectral
      density or the residence time difference (RTD) in two sensor states. Recently,
      the noise activated nonlinear dynamic sensors driven only by noise based on RTD
      technique have been proposed. Here, we present experimental results of dc voltage
      measurements by noise-driven bistable sensor based on electronic Chua's circuit
      operating in a chaotic regime where two single scroll attractors coexist. The
      output of the sensor is quantified by the proportion of the time the sensor stays
      in one state to the total observation time and by the spike-count rate with
      spikes defined by crossings between attractors. The relationship between the
      stimuli and particular observable for different noise intensities is obtained,
      the usefulness of each coding scheme is discussed, and the optimal noise
      intensity for detection is indicated. It is shown that the obtained relationship
      is the same for any observation time when population coding is used. The optimal
      time window for both detection and the number of units in population coding is
      found. Our results may be useful for analyses and understanding of the neural
      activity and in designing bistable storage elements at length scales where
      thermal fluctuations drastically increase and the effect of noise must be taken
      into consideration.

PMID- 29195300
TI  - Pseudo-spatial coherence resonance in an excitable laser with long delayed
      feedback.
AB  - The effect of noise in an excitable semiconductor laser with feedback is studied
      in the framework of the spatio-temporal representation of long delayed systems.
      Propagation, noise-induced creation, and destruction of excitable pulses in the
      pseudo time are observed. The addition of a variable quantity of noise leads to
      the occurrence of a phenomenon that we term "pseudo-spatial coherence resonance."
      A phenomenological model well describes the system and allows for a comparison
      with the experimental observations. A simple Monte Carlo approach is also
      introduced and permits to explain the features observed in terms of the key
      dynamical ingredients of the physical system.

PMID- 29195301
TI  - Drifting cavity solitons and dissipative rogue waves induced by time-delayed
      feedback in Kerr optical frequency comb and in all fiber cavities.
AB  - Time-delayed feedback plays an important role in the dynamics of spatially
      extended systems. In this contribution, we consider the generic Lugiato-Lefever
      model with delay feedback that describes Kerr optical frequency comb in all fiber
      cavities. We show that the delay feedback strongly impacts the spatiotemporal
      dynamical behavior resulting from modulational instability by (i) reducing the
      threshold associated with modulational instability and by (ii) decreasing the
      critical frequency at the onset of this instability. We show that for moderate
      input intensities it is possible to generate drifting cavity solitons with an
      asymmetric radiation emitted from the soliton tails. Finally, we characterize the
      formation of rogue waves induced by the delay feedback.

PMID- 29195302
TI  - Transient behavior between multi-cell flow states in ferrofluidic Taylor-Couette
      flow.
AB  - We investigate transient behaviors induced by magnetic fields on the dynamics of
      the flow of a ferrofluid in the gap between two concentric, independently
      rotating cylinders. Without applying any magnetic fields, we uncover emergence of
      flow states constituted by a combination of a localized spiral state in the top
      and bottom of the annulus and different multi-cell flow states with toroidally
      closed vortices in the interior of the bulk. However, when a magnetic field is
      presented, we observe the transient behaviors between multi-cell states passing
      through two critical thresholds in a strength of an axial (transverse) magnetic
      field. Before the first critical threshold of a magnetic field strength, multi
      stable states with different number of cells could be observed. After the first
      critical threshold, we find the transient behavior between the three- and two
      cell flow states. For more strength of magnetic field or after the second
      critical threshold, we discover that multi-cell states are disappeared and a
      localized spiral state remains to be stimulated. The studied transient behavior
      could be understood by the investigation of various quantities including a modal
      kinetic energy, a mode amplitude of the radial velocity, wavenumber, angular
      momentum, and torque. In addition, the emergence of new flow states and the
      transient behavior between their states in ferrofluidic flows indicate that
      richer and potentially controllable dynamics through magnetic fields could be
      possible in ferrofluic flow.

PMID- 29195303
TI  - The influence of parametric and external noise in act-and-wait control with
      delayed feedback.
AB  - We apply several novel semi-analytic approaches for characterizing and
      calculating the effects of noise in a system with act-and-wait control. For
      concrete illustration, we apply these to a canonical balance model for an
      inverted pendulum to study the combined effect of delay and noise within the act
      and-wait setting. While the act-and-wait control facilitates strong stabilization
      through deadbeat control, a comparison of different models with continuous vs.
      discrete updating of the control strategy in the active period illustrates how
      delays combined with the imprecise application of the control can seriously
      degrade the performance. We give several novel analyses of a generalized act-and
      wait control strategy, allowing flexibility in the updating of the control
      strategy, in order to understand the sensitivities to delays and random
      fluctuations. In both the deterministic and stochastic settings, we give
      analytical and semi-analytical results that characterize and quantify the
      dynamics of the system. These results include the size and shape of stability
      regions, densities for the critical eigenvalues that capture the rate of reaching
      the desired stable equilibrium, and amplification factors for sustained
      fluctuations in the context of external noise. They also provide the dependence
      of these quantities on the length of the delay and the active period. In
      particular, we see that the combined influence of delay, parametric error, or
      external noise and on-off control can qualitatively change the dynamics, thus
      reducing the robustness of the control strategy. We also capture the dependence
      on how frequently the control is updated, allowing an interpolation between
      continuous and frequent updating. In addition to providing insights for these
      specific models, the methods we propose are generalizable to other settings with
      noise, delay, and on-off control, where analytical techniques are otherwise
      severely scarce.

PMID- 29195304
TI  - Role of dynamical injection locking and characteristic pulse events for low
      frequency fluctuations in semiconductor lasers.
AB  - We investigate the dynamics of semiconductor lasers subject to time-delayed
      optical feedback from the perspective of dynamical self-injection locking. Based
      on the Lang-Kobayashi model, we perform an analysis of the well-known Low
      Frequency Fluctuations (LFFs) in the frequency-intensity plane. Moreover, we
      investigate a recently found dynamical regime of fragmented LFFs by means of a
      locking-range analysis, spectral comparison and precursor pulse identification.
      We show that LFF dynamics can be explained by dynamical optical injection locking
      due to the delayed optical feedback. Moreover, the fragmented LFFs occur due to a
      re-injection locking induced by a particular optical pulse structure in the
      chaotic feedback dynamics. This is corroborated by experiments with a
      semiconductor laser experiencing delayed feedback from an optical fiber loop. The
      dynamical nature of the feedback injection results in an eventual loss, but also
      possible regaining, of the locking, explaining the recently observed phenomenon
      of fragmented LFFs.

PMID- 29195305
TI  - Opinion evolution in different social acquaintance networks.
AB  - Social acquaintance networks influenced by social culture and social policy have
      a great impact on public opinion evolution in daily life. Based on the
      differences between socio-culture and social policy, three different social
      acquaintance networks (kinship-priority acquaintance network, independence
      priority acquaintance network, and hybrid acquaintance network) incorporating
      heredity proportion ph and variation proportion pv are proposed in this paper.
      Numerical experiments are conducted to investigate network topology and different
      phenomena during opinion evolution, using the Deffuant model. We found that in
      kinship-priority acquaintance networks, similar to the Chinese traditional
      acquaintance networks, opinions always achieve fragmentation, resulting in the
      formation of multiple large clusters and many small clusters due to the fact that
      individuals believe more in their relatives and live in a relatively closed
      environment. In independence-priority acquaintance networks, similar to Western
      acquaintance networks, the results are similar to those in the kinship-priority
      acquaintance network. In hybrid acquaintance networks, similar to the Chinese
      modern acquaintance networks, only a few clusters are formed indicating that in
      modern China, opinions are more likely to reach consensus on a large scale. These
      results are similar to the opinion evolution phenomena in modern society, proving
      the rationality and applicability of network models combined with social culture
      and policy. We also found a threshold curve pv+2ph=2.05 in the results for the
      final opinion clusters and evolution time. Above the threshold curve, opinions
      could easily reach consensus. Based on the above experimental results, a culture
      policy-driven mechanism for the opinion dynamic is worth promoting in this paper,
      that is, opinion dynamics can be driven by different social cultures and policies
      through the influence of heredity and variation in interpersonal relationship
      networks. This finding is of great significance for predicting opinion evolution
      under different acquaintance networks and formulating reasonable policies based
      on cultural characteristics to guide public opinion.

PMID- 29195306
TI  - Exploring the route to measure synchronization in non-linearly coupled
      Hamiltonian systems.
AB  - Measure Synchronization is a general term used for weak synchronization in
      Hamiltonian systems. Route to measure synchronization in a system of two non
      linearly coupled one-dimensional oscillators, the potential of which is
      represented by the Pullen-Edmonds Potential is investigated on the basis of
      numerical computation. Transitions to measure synchronization and
      unsynchronization, both quasiperiodic and chaotic, are investigated and
      distinguished on the basis of the variation of average bare energies, average
      interaction energy, root-mean-square value of oscillations, phase difference, and
      frequencies with the coupling strength. A suitable order parameter to identify
      and characterize both quasiperiodic and chaotic measure synchronous states is
      sought, and drawbacks of the various order parameters, suggested previously, are
      discussed.

PMID- 29195307
TI  - Mean, covariance, and effective dimension of stochastic distributed delay
      dynamics.
AB  - Dynamical models are often required to incorporate both delays and noise.
      However, the inherently infinite-dimensional nature of delay equations makes
      formal solutions to stochastic delay differential equations (SDDEs) challenging.
      Here, we present an approach, similar in spirit to the analysis of functional
      differential equations, but based on finite-dimensional matrix operators. This
      results in a method for obtaining both transient and stationary solutions that is
      directly amenable to computation, and applicable to first order differential
      systems with either discrete or distributed delays. With fewer assumptions on the
      system's parameters than other current solution methods and no need to be near a
      bifurcation, we decompose the solution to a linear SDDE with arbitrary
      distributed delays into natural modes, in effect the eigenfunctions of the
      differential operator, and show that relatively few modes can suffice to
      approximate the probability density of solutions. Thus, we are led to conclude
      that noise makes these SDDEs effectively low dimensional, which opens the
      possibility of practical definitions of probability densities over their solution
      space.

PMID- 29195308
TI  - Oscillatory dynamics of an intravenous glucose tolerance test model with delay
      interval.
AB  - Type 2 diabetes mellitus (T2DM) has become prevalent pandemic disease in view of
      the modern life style. Both diabetic population and health expenses grow rapidly
      according to American Diabetes Association. Detecting the potential onset of T2DM
      is an essential focal point in the research of diabetes mellitus. The intravenous
      glucose tolerance test (IVGTT) is an effective protocol to determine the insulin
      sensitivity, glucose effectiveness, and pancreatic beta-cell functionality,
      through the analysis and parameter estimation of a proper differential equation
      model. Delay differential equations have been used to study the complex
      physiological phenomena including the glucose and insulin regulations. In this
      paper, we propose a novel approach to model the time delay in IVGTT modeling.
      This novel approach uses two parameters to simulate not only both discrete time
      delay and distributed time delay in the past interval, but also the time delay
      distributed in a past sub-interval. Normally, larger time delay, either a
      discrete or a distributed delay, will destabilize the system. However, we find
      that time delay over a sub-interval might not. We present analytically some basic
      model properties, which are desirable biologically and mathematically. We show
      that this relatively simple model provides good fit to fluctuating patient data
      sets and reveals some intriguing dynamics. Moreover, our numerical simulation
      results indicate that our model may remove the defect in well known Minimal
      Model, which often overestimates the glucose effectiveness index.

PMID- 29195309
TI  - Class-A mode-locked lasers: Fundamental solutions.
AB  - We consider a delay differential equation (DDE) model for mode-locked operation
      in class-A semiconductor lasers containing both gain and absorber sections. The
      material processes are adiabatically eliminated as these are considered fast in
      comparison to the delay time for a long cavity device. We determine the steady
      states and analyze their bifurcations using DDE-BIFTOOL [Engelborghs et al., ACM
      Trans. Math. Software 28, 1 (2002)]. Multiple forms of coexistence,
      transformation, and hysteretic behavior of stable steady states and fundamental
      periodic regimes are discussed in bifurcation diagrams.

PMID- 29195310
TI  - Delay dynamics of neuromorphic optoelectronic nanoscale resonators: Perspectives
      and applications.
AB  - With the recent exponential growth of applications using artificial intelligence
      (AI), the development of efficient and ultrafast brain-like (neuromorphic)
      systems is crucial for future information and communication technologies. While
      the implementation of AI systems using computer algorithms of neural networks is
      emerging rapidly, scientists are just taking the very first steps in the
      development of the hardware elements of an artificial brain, specifically
      neuromorphic microchips. In this review article, we present the current state of
      the art of neuromorphic photonic circuits based on solid-state optoelectronic
      oscillators formed by nanoscale double barrier quantum well resonant tunneling
      diodes. We address, both experimentally and theoretically, the key dynamic
      properties of recently developed artificial solid-state neuron microchips with
      delayed perturbations and describe their role in the study of neural activity and
      regenerative memory. This review covers our recent research work on excitable and
      delay dynamic characteristics of both single and autaptic (delayed) artificial
      neurons including all-or-none response, spike-based data encoding, storage,
      signal regeneration and signal healing. Furthermore, the neural responses of
      these neuromorphic microchips display all the signatures of extended spatio
      temporal localized structures (LSs) of light, which are reviewed here in detail.
      By taking advantage of the dissipative nature of LSs, we demonstrate potential
      applications in optical data reconfiguration and clock and timing at high-speeds
      and with short transients. The results reviewed in this article are a key enabler
      for the development of high-performance optoelectronic devices in future high
      speed brain-inspired optical memories and neuromorphic computing.

PMID- 29195311
TI  - Chimera states in multi-strain epidemic models with temporary immunity.
AB  - We investigate a time-delayed epidemic model for multi-strain diseases with
      temporary immunity. In the absence of cross-immunity between strains, dynamics of
      each individual strain exhibit emergence and annihilation of limit cycles due to
      a Hopf bifurcation of the endemic equilibrium, and a saddle-node bifurcation of
      limit cycles depending on the time delay associated with duration of temporary
      immunity. Effects of all-to-all and non-local coupling topologies are
      systematically investigated by means of numerical simulations, and they suggest
      that cross-immunity is able to induce a diverse range of complex dynamical
      behaviors and synchronization patterns, including discrete traveling waves,
      solitary states, and amplitude chimeras. Interestingly, chimera states are
      observed for narrower cross-immunity kernels, which can have profound
      implications for understanding the dynamics of multi-strain diseases.

PMID- 29195312
TI  - Introduction to Focus Issue: Time-delay dynamics.
AB  - The field of dynamical systems with time delay is an active research area that
      connects practically all scientific disciplines including mathematics, physics,
      engineering, biology, neuroscience, physiology, economics, and many others. This
      Focus Issue brings together contributions from both experimental and theoretical
      groups and emphasizes a large variety of applications. In particular, lasers and
      optoelectronic oscillators subject to time-delayed feedbacks have been explored
      by several authors for their specific dynamical output, but also because they are
      ideal test-beds for experimental studies of delay induced phenomena. Topics
      include the control of cavity solitons, as light spots in spatially extended
      systems, new devices for chaos communication or random number generation, higher
      order locking phenomena between delay and laser oscillation period, and
      systematic bifurcation studies of mode-locked laser systems. Moreover, two
      original theoretical approaches are explored for the so-called Low Frequency
      Fluctuations, a particular chaotical regime in laser output which has attracted a
      lot of interest for more than 30 years. Current hot problems such as the
      synchronization properties of networks of delay-coupled units, novel
      stabilization techniques, and the large delay limit of a delay differential
      equation are also addressed in this special issue. In addition, analytical and
      numerical tools for bifurcation problems with or without noise and two reviews on
      concrete questions are proposed. The first review deals with the rich dynamics of
      simple delay climate models for El Nino Southern Oscillations, and the second
      review concentrates on neuromorphic photonic circuits where optical elements are
      used to emulate spiking neurons. Finally, two interesting biological problems are
      considered in this Focus Issue, namely, multi-strain epidemic models and the
      interaction of glucose and insulin for more effective treatment.

PMID- 29195313
TI  - Chaotic bursting in semiconductor lasers.
AB  - We investigate the dynamic mechanisms for low frequency fluctuations in
      semiconductor lasers subjected to delayed optical feedback, using the Lang
      Kobayashi model. This system of delay differential equations displays pronounced
      envelope dynamics, ranging from erratic, so called low frequency fluctuations to
      regular pulse packages, if the time scales of fast oscillations and envelope
      dynamics are well separated. We investigate the parameter regions where low
      frequency fluctuations occur and compute their Lyapunov spectra. Using the
      geometric singular perturbation theory, we study this intermittent chaotic
      behavior and characterize these solutions as bursting slow-fast oscillations.

PMID- 29195314
TI  - Time-delayed feedback control of coherence resonance chimeras.
AB  - Using the model of a FitzHugh-Nagumo system in the excitable regime, we
      investigate the influence of time-delayed feedback on noise-induced chimera
      states in a network with nonlocal coupling, i.e., coherence resonance chimeras.
      It is shown that time-delayed feedback allows for the control of the range of
      parameter values where these chimera states occur. Moreover, for the feedback
      delay close to the intrinsic period of the system, we find a novel regime which
      we call period-two coherence resonance chimera.

PMID- 29195315
TI  - The impact of propagation and processing delays on amplitude and oscillation
      deaths in the presence of symmetry-breaking coupling.
AB  - We numerically investigate the impacts of both propagation and processing delays
      on the emergences of amplitude death (AD) and oscillation death (OD) in one
      system of two Stuart-Landau oscillators with symmetry-breaking coupling. In
      either the absence of or the presence of propagation delay, the processing delay
      destabilizes both AD and OD by revoking the stability of the stable homogenous
      and inhomogenous steady states. In the AD to OD transition, the processing delay
      destabilizes first OD from large values of coupling strength until its stable
      regime completely disappears and then AD from both the upper and lower bounds of
      the stable coupling interval. Our numerical study sheds new insight lights on the
      understanding of nontrivial effects of time delays on dynamic activity of coupled
      nonlinear systems.

PMID- 29195316
TI  - Computing aggregate properties of preimages for 2D cellular automata.
AB  - Computing properties of the set of precursors of a given configuration is a
      common problem underlying many important questions about cellular automata.
      Unfortunately, such computations quickly become intractable in dimension greater
      than one. This paper presents an algorithm-incremental aggregation-that can
      compute aggregate properties of the set of precursors exponentially faster than
      naive approaches. The incremental aggregation algorithm is demonstrated on two
      problems from the two-dimensional binary Game of Life cellular automaton:
      precursor count distributions and higher-order mean field theory coefficients. In
      both cases, incremental aggregation allows us to obtain new results that were
      previously beyond reach.

PMID- 29195317
TI  - Climate models with delay differential equations.
AB  - A fundamental challenge in mathematical modelling is to find a model that
      embodies the essential underlying physics of a system, while at the same time
      being simple enough to allow for mathematical analysis. Delay differential
      equations (DDEs) can often assist in this goal because, in some cases, only the
      delayed effects of complex processes need to be described and not the processes
      themselves. This is true for some climate systems, whose dynamics are driven in
      part by delayed feedback loops associated with transport times of mass or energy
      from one location of the globe to another. The infinite-dimensional nature of
      DDEs allows them to be sufficiently complex to reproduce realistic dynamics
      accurately with a small number of variables and parameters. In this paper, we
      review how DDEs have been used to model climate systems at a conceptual level.
      Most studies of DDE climate models have focused on gaining insights into either
      the global energy balance or the fundamental workings of the El Nino Southern
      Oscillation (ENSO) system. For example, studies of DDEs have led to proposed
      mechanisms for the interannual oscillations in sea-surface temperature that is
      characteristic of ENSO, the irregular behaviour that makes ENSO difficult to
      forecast and the tendency of El Nino events to occur near Christmas. We also
      discuss the tools used to analyse such DDE models. In particular, the recent
      development of continuation software for DDEs makes it possible to explore large
      regions of parameter space in an efficient manner in order to provide a "global
      picture" of the possible dynamics. We also point out some directions for future
      research, including the incorporation of non-constant delays, which we believe
      could improve the descriptive power of DDE climate models.

PMID- 29195318
TI  - Experimental characterization of the transition to coherence collapse in a
      semiconductor laser with optical feedback.
AB  - Semiconductor lasers with time-delayed optical feedback display a wide range of
      dynamical regimes, which have found various practical applications. They also
      provide excellent testbeds for data analysis tools for characterizing complex
      signals. Recently, several of us have analyzed experimental intensity time-traces
      and quantitatively identified the onset of different dynamical regimes, as the
      laser current increases. Specifically, we identified the onset of low-frequency
      fluctuations (LFFs), where the laser intensity displays abrupt dropouts, and the
      onset of coherence collapse (CC), where the intensity fluctuations are highly
      irregular. Here we map these regimes when both, the laser current and the
      feedback strength vary. We show that the shape of the distribution of intensity
      fluctuations (characterized by the standard deviation, the skewness, and the
      kurtosis) allows to distinguish among noise, LFFs and CC, and to quantitatively
      determine (in spite of the gradual nature of the transitions) the boundaries of
      the three regimes. Ordinal analysis of the inter-dropout time intervals
      consistently identifies the three regimes occurring in the same parameter regions
      as the analysis of the intensity distribution. Simulations of the well-known time
      delayed Lang-Kobayashi model are in good qualitative agreement with the
      observations.

PMID- 29195319
TI  - Controlling Mackey-Glass chaos.
AB  - The Mackey-Glass equation is the representative example of delay induced chaotic
      behavior. Here, we propose various control mechanisms so that otherwise erratic
      solutions are forced to converge to the positive equilibrium or to a periodic
      orbit oscillating around that equilibrium. We take advantage of some recent
      results of the delay differential literature, when a sufficiently large domain of
      the phase space has been shown to be attractive and invariant, where the system
      is governed by monotone delayed feedback and chaos is not possible due to some
      Poincare-Bendixson type results. We systematically investigate what control
      mechanisms are suitable to drive the system into such a situation and prove that
      constant perturbation, proportional feedback control, Pyragas control, and state
      dependent delay control can all be efficient to control Mackey-Glass chaos with
      properly chosen control parameters.

PMID- 29195320
TI  - Symmetry, Hopf bifurcation, and the emergence of cluster solutions in time
      delayed neural networks.
AB  - We consider the networks of N identical oscillators with time delayed, global
      circulant coupling, modeled by a system of delay differential equations with ZN
      symmetry. We first study the existence of Hopf bifurcations induced by the
      coupling time delay and then use symmetric Hopf bifurcation theory to determine
      how these bifurcations lead to different patterns of symmetric cluster
      oscillations. We apply our results to a case study: a network of FitzHugh-Nagumo
      neurons with diffusive coupling. For this model, we derive the asymptotic
      stability, global asymptotic stability, absolute instability, and stability
      switches of the equilibrium point in the plane of coupling time delay (tau) and
      excitability parameter (a). We investigate the patterns of cluster oscillations
      induced by the time delay and determine the direction and stability of the
      bifurcating periodic orbits by employing the multiple timescales method and
      normal form theory. We find that in the region where stability switching occurs,
      the dynamics of the system can be switched from the equilibrium point to any
      symmetric cluster oscillation, and back to equilibrium point as the time delay is
      increased.

PMID- 29195321
TI  - Anticipated and zero-lag synchronization in motifs of delay-coupled systems.
AB  - Anticipated and zero-lag synchronization have been observed in different
      scientific fields. In the brain, they might play a fundamental role in
      information processing, temporal coding and spatial attention. Recent numerical
      work on anticipated and zero-lag synchronization studied the role of delays.
      However, an analytical understanding of the conditions for these phenomena
      remains elusive. In this paper, we study both phenomena in systems with small
      delays. By performing a phase reduction and studying phase locked solutions, we
      uncover the functional relation between the delay, excitation and inhibition for
      the onset of anticipated synchronization in a sender-receiver-interneuron motif.
      In the case of zero-lag synchronization in a chain motif, we determine the
      stability conditions. These analytical solutions provide an excellent prediction
      of the phase-locked regimes of Hodgkin-Huxley models and Roessler oscillators.

PMID- 29195322
TI  - Reduced alpha-stable dynamics for multiple time scale systems forced with
      correlated additive and multiplicative Gaussian white noise.
AB  - Stochastic averaging problems with Gaussian forcing have been the subject of
      numerous studies, but far less attention has been paid to problems with infinite
      variance stochastic forcing, such as an alpha-stable noise process. It has been
      shown that simple linear systems driven by correlated additive and multiplicative
      (CAM) Gaussian noise, which emerge in the context of reduced atmosphere and ocean
      dynamics, have infinite variance in certain parameter regimes. In this study, we
      consider the stochastic averaging of systems where a linear CAM noise process in
      the infinite variance parameter regime drives a comparatively slow process. We
      use (semi)-analytical approximations combined with numerical illustrations to
      compare the averaged process to one that is forced by a white alpha-stable
      process, demonstrating consistent properties in the case of large time-scale
      separation. We identify the conditions required for the fast linear CAM process
      to have such an influence in driving a slower process and then derive an
      (effectively) equivalent fast, infinite-variance process for which an existing
      stochastic averaging approximation is readily applied. The results are
      illustrated using numerical simulations of a set of example systems.

PMID- 29195323
TI  - Small-world networks exhibit pronounced intermittent synchronization.
AB  - We report the phenomenon of temporally intermittently synchronized and
      desynchronized dynamics in Watts-Strogatz networks of chaotic Rossler
      oscillators. We consider topologies for which the master stability function (MSF)
      predicts stable synchronized behaviour, as the rewiring probability (p) is tuned
      from 0 to 1. MSF essentially utilizes the largest non-zero Lyapunov exponent
      transversal to the synchronization manifold in making stability considerations,
      thereby ignoring the other Lyapunov exponents. However, for an N-node networked
      dynamical system, we observe that the difference in its Lyapunov spectra
      (corresponding to the N - 1 directions transversal to the synchronization
      manifold) is crucial and serves as an indicator of the presence of intermittently
      synchronized behaviour. In addition to the linear stability-based (MSF) analysis,
      we further provide global stability estimate in terms of the fraction of state
      space volume shared by the intermittently synchronized state, as p is varied from
      0 to 1. This fraction becomes appreciably large in the small-world regime, which
      is surprising, since this limit has been otherwise considered optimal for
      synchronized dynamics. Finally, we characterize the nature of the observed
      intermittency and its dominance in state-space as network rewiring probability
      (p) is varied.

PMID- 29195324
TI  - Using periodic orbits to compute chaotic transport rates between resonance zones.
AB  - Transport properties of chaotic systems are computable from data extracted from
      periodic orbits. Given a sufficient number of periodic orbits, the escape rate
      can be computed using the spectral determinant, a function that incorporates the
      eigenvalues and periods of periodic orbits. The escape rate computed from
      periodic orbits converges to the true value as more and more periodic orbits are
      included. Escape from a given region of phase space can be computed by
      considering only periodic orbits that lie within the region. An accurate symbolic
      dynamics along with a corresponding partitioning of phase space is useful for
      systematically obtaining all periodic orbits up to a given period, to ensure that
      no important periodic orbits are missing in the computation. Homotopic lobe
      dynamics (HLD) is an automated technique for computing accurate partitions and
      symbolic dynamics for maps using the topological forcing of intersections of
      stable and unstable manifolds of a few periodic anchor orbits. In this study, we
      apply the HLD technique to compute symbolic dynamics and periodic orbits, which
      are then used to find escape rates from different regions of phase space for the
      Henon map. We focus on computing escape rates in parameter ranges spanning
      hyperbolic plateaus, which are parameter intervals where the dynamics is
      hyperbolic and the symbolic dynamics does not change. After the periodic orbits
      are computed for a single parameter value within a hyperbolic plateau, periodic
      orbit continuation is used to compute periodic orbits over an interval that spans
      the hyperbolic plateau. The escape rates computed from a few thousand periodic
      orbits agree with escape rates computed from Monte Carlo simulations requiring
      hundreds of billions of orbits.

PMID- 29195325
TI  - Stochastic resonance in a delayed triple-well potential driven by correlated
      noises.
AB  - In this paper, we investigate stochastic resonance (SR) in a delayed triple-well
      potential subject to correlated noises and a harmonic signal. The stationary
      probability density, together with the response amplitude of the system, is
      obtained by using the small time delay approximation. It is found that the time
      delay, noise intensities, and the cross-correlation between noises can induce the
      occurrence of the transition. Moreover, the appropriate choice of noise
      intensities and time delay can improve the output of the system, enhance the SR
      effect, and lead to the phenomenon of noise enhanced stability. Especially, the
      stochastic multi-resonance phenomenon is observed when the multiplicative and
      additive noises are correlated. Finally, the theoretical results are well
      verified through numerical simulations.

PMID- 29195326
TI  - Multipulse dynamics of a passively mode-locked semiconductor laser with delayed
      optical feedback.
AB  - Passively mode-locked semiconductor lasers are compact, inexpensive sources of
      short light pulses of high repetition rates. In this work, we investigate the
      dynamics and bifurcations arising in such a device under the influence of time
      delayed optical feedback. This laser system is modelled by a system of delay
      differential equations, which includes delay terms associated with the laser
      cavity and feedback loop. We make use of specialised path continuation software
      for delay differential equations to analyse the regime of short feedback delays.
      Specifically, we consider how the dynamics and bifurcations depend on the pump
      current of the laser, the feedback strength, and the feedback delay time. We show
      that an important role is played by resonances between the mode-locking
      frequencies and the feedback delay time. We find feedback-induced harmonic mode
      locking and show that a mismatch between the fundamental frequency of the laser
      and that of the feedback cavity can lead to multi-pulse or quasiperiodic
      dynamics. The quasiperiodic dynamics exhibit a slow modulation, on the time scale
      of the gain recovery rate, which results from a beating with the frequency
      introduced in the associated torus bifurcations and leads to gain competition
      between multiple pulse trains within the laser cavity. Our results also have
      implications for the case of large feedback delay times, where a complete
      bifurcation analysis is not practical. Namely, for increasing delay, there is an
      ever-increasing degree of multistability between mode-locked solutions due to the
      frequency pulling effect.

PMID- 29195327
TI  - Stochastic modelling of non-stationary financial assets.
AB  - We model non-stationary volume-price distributions with a log-normal distribution
      and collect the time series of its two parameters. The time series of the two
      parameters are shown to be stationary and Markov-like and consequently can be
      modelled with Langevin equations, which are derived directly from their series of
      values. Having the evolution equations of the log-normal parameters, we
      reconstruct the statistics of the first moments of volume-price distributions
      which fit well the empirical data. Finally, the proposed framework is general
      enough to study other non-stationary stochastic variables in other research
      fields, namely, biology, medicine, and geology.

PMID- 29195328
TI  - Delayed feedback control of self-mobile cavity solitons in a wide-aperture laser
      with a saturable absorber.
AB  - We investigate the spatiotemporal dynamics of cavity solitons in a broad area
      vertical-cavity surface-emitting laser with saturable absorption subjected to
      time-delayed optical feedback. Using a combination of analytical, numerical, and
      path continuation methods, we analyze the bifurcation structure of stationary and
      moving cavity solitons and identify two different types of traveling localized
      solutions, corresponding to slow and fast motion. We show that the delay impacts
      both stationary and moving solutions either causing drifting and wiggling
      dynamics of initially stationary cavity solitons or leading to stabilization of
      intrinsically moving solutions. Finally, we demonstrate that the fast cavity
      solitons can be associated with a lateral mode-locking regime in a broad-area
      laser with a single longitudinal mode.

PMID- 29195329
TI  - Delay induced high order locking effects in semiconductor lasers.
AB  - Multiple time scales appear in many nonlinear dynamical systems. Semiconductor
      lasers, in particular, provide a fertile testing ground for multiple time scale
      dynamics. For solitary semiconductor lasers, the two fundamental time scales are
      the cavity repetition rate and the relaxation oscillation frequency which is a
      characteristic of the field-matter interaction in the cavity. Typically, these
      two time scales are of very different orders, and mutual resonances do not occur.
      Optical feedback endows the system with a third time scale: the external cavity
      repetition rate. This is typically much longer than the device cavity repetition
      rate and suggests the possibility of resonances with the relaxation oscillations.
      We show that for lasers with highly damped relaxation oscillations, such
      resonances can be obtained and lead to spontaneous mode-locking. Two different
      laser types--a quantum dot based device and a quantum well based device-are
      analysed experimentally yielding qualitatively identical dynamics. A rate
      equation model is also employed showing an excellent agreement with the
      experimental results.

PMID- 29195330
TI  - Nonlinear dynamics of an elliptic vortex embedded in an oscillatory shear flow.
AB  - The nonlinear dynamics of an elliptic vortex subjected to a time-periodic linear
      external shear flow is studied numerically. Making use of the ideas from the
      theory of nonlinear resonance overlaps, the study focuses on the appearance of
      chaotic regimes in the ellipse dynamics. When the superimposed flow is
      stationary, two general types of the steady-state phase portrait are considered:
      one that features a homoclinic separatrix delineating bounded and unbounded phase
      trajectories and one without a separatrix (all the phase trajectories are bounded
      in a periodic domain). When the external flow is time-periodic, the ensuing
      nonlinear dynamics differs significantly in both cases. For the case with a
      separatrix and two distinct types of phase trajectories: bounded and unbounded,
      the effect of the most influential nonlinear resonance with the winding number of
      1:1 is analyzed in detail. Namely, the process of occupying the central stability
      region associated with the steady-state elliptic critical point by the stability
      region associated with the nonlinear resonance of 1:1 as the perturbation
      frequency gradually varies is investigated. A stark increase in the persistence
      of the central regular dynamics region against perturbation when the resonance of
      1:1 associated stability region occupies the region associated with the steady
      state elliptic critical point is observed. An analogous persistence of the
      regular motion occurs for higher perturbation frequencies when the corresponding
      stability islands reach the central stability region associated with the steady
      state elliptic point. An analysis for the case with the resonance of 1:2 is
      presented. For the second case with only bounded phase trajectories and,
      therefore, no separatrix, the appearance of much bigger stability islands
      associated with nonlinear resonances compared with the case with a separatrix is
      reported.

PMID- 29195331
TI  - Solitons of the coupled Schrodinger-Korteweg-de Vries system with arbitrary
      strengths of the nonlinearity and dispersion.
AB  - New two-component soliton solutions of the coupled high-frequency (HF)-low
      frequency (LF) system, based on Schrodinger-Korteweg-de Vries (KdV) system with
      the Zakharov's coupling, are obtained for arbitrary relative strengths of the
      nonlinearity and dispersion in the LF component. The complex HF field is governed
      by the linear Schrodinger equation with a potential generated by the real LF
      component, which, in turn, is governed by the KdV equation including the
      ponderomotive coupling term, representing the feedback of the HF field onto the
      LF component. First, we study the evolution of pulse-shaped pulses by means of
      direct simulations. In the case when the dispersion of the LF component is weak
      in comparison to its nonlinearity, the input gives rise to several solitons in
      which the HF component is much broader than its LF counterpart. In the opposite
      case, the system creates a single soliton with approximately equal widths of both
      components. Collisions between stable solitons are studied too, with a conclusion
      that the collisions are inelastic, with a greater soliton getting still stronger,
      and the smaller one suffering further attenuation. Robust intrinsic modes are
      excited in the colliding solitons. A new family of approximate analytical two
      component soliton solutions with two free parameters is found for an arbitrary
      relative strength of the nonlinearity and dispersion of the LF component,
      assuming weak feedback of the HF field onto the LF component. Further, a one
      parameter (non-generic) family of exact bright-soliton solutions, with mutually
      proportional HF and LF components, is produced too. Intrinsic dynamics of the two
      component solitons, induced by a shift of their HF component against the LF one,
      is also studied, by means of numerical simulations, demonstrating excitation of a
      robust intrinsic mode. In addition to the above-mentioned results for LF
      dominated two-component solitons, which always run in one (positive) velocities,
      we produce HF-dominated soliton complexes, which travel in the opposite
      (negative) direction. They are obtained in a numerical form and by means of a
      quasi-adiabatic analytical approximation. The solutions with positive and
      negative velocities correspond, respectively, to super- and subsonic Davydov
      Scott solitons.

PMID- 29195332
TI  - Models of spin-orbit-coupled oligomers.
AB  - We address the stability and dynamics of eigenmodes in linearly shaped strings
      (dimers, trimers, tetramers, and pentamers) built of droplets in a binary Bose
      Einstein condensate (BEC). The binary BEC is composed of atoms in two pseudo-spin
      states with attractive interactions, dressed by properly arranged laser fields,
      which induce the (pseudo-) spin-orbit (SO) coupling. We demonstrate that the SO
      coupling terms help to create eigenmodes of particular types in the strings.
      Dimer, trimer, and pentamer eigenmodes of the linear system, which correspond to
      the zero eigenvalue (EV, alias chemical potential) extend into the nonlinear
      ones, keeping an exact analytical form, while tetramers do not admit such a
      continuation, because the respective spectrum does not contain a zero EV.
      Stability areas of these modes shrink with the increasing nonlinearity. Besides
      these modes, other types of nonlinear states, which are produced by the
      continuation of their linear counterparts corresponding to some nonzero EVs, are
      found in a numerical form (including ones for the tetramer system). They are
      stable in nearly entire existence regions in trimer and pentamer systems, but
      only in a very small area for the tetramers. Similar results are also obtained,
      but not displayed in detail, for hexa- and septamers.

PMID- 29195334
TI  - Local bifurcations in differential equations with state-dependent delay.
AB  - A common task when analysing dynamical systems is the determination of normal
      forms near local bifurcations of equilibria. As most of these normal forms have
      been classified and analysed, finding which particular class of normal form one
      encounters in a numerical bifurcation study guides follow-up computations. This
      paper builds on normal form algorithms for equilibria of delay differential
      equations with constant delay that were developed and implemented in DDE-Biftool
      recently. We show how one can extend these methods to delay-differential
      equations with state-dependent delay (sd-DDEs). Since higher degrees of
      regularity of local center manifolds are still open for sd-DDEs, we give an
      independent (still only partial) argument which phenomena from the truncated
      normal must persist in the full sd-DDE. In particular, we show that all invariant
      manifolds with a sufficient degree of normal hyperbolicity predicted by the
      normal form exist also in the full sd-DDE.

PMID- 29195333
TI  - Synchronization stability and pattern selection in a memristive neuronal network.
AB  - Spatial pattern formation and selection depend on the intrinsic self-organization
      and cooperation between nodes in spatiotemporal systems. Based on a memory neuron
      model, a regular network with electromagnetic induction is proposed to
      investigate the synchronization and pattern selection. In our model, the
      memristor is used to bridge the coupling between the magnetic flux and the
      membrane potential, and the induction current results from the time-varying
      electromagnetic field contributed by the exchange of ion currents and the
      distribution of charged ions. The statistical factor of synchronization predicts
      the transition of synchronization and pattern stability. The bifurcation analysis
      of the sampled time series for the membrane potential reveals the mode transition
      in electrical activity and pattern selection. A formation mechanism is outlined
      to account for the emergence of target waves. Although an external stimulus is
      imposed on each neuron uniformly, the diversity in the magnetic flux and the
      induction current leads to emergence of target waves in the studied network.

PMID- 29195335
TI  - Mapping of external cavity modes for a laser diode subject to phase-conjugate
      feedback.
AB  - We numerically investigate the dynamics of a semiconductor laser subject to phase
      conjugate optical feedback. We explore the effects of the laser model and
      feedback parameters for the generation of time-periodic oscillations of the
      output power at harmonics of the external cavity frequency, i.e., dynamical
      solutions that have been named external cavity modes. We point out that both the
      experimentally tunable and other parameters have an influence on the frequency of
      such dynamics. Since the delay has to exist, it is not the relevant parameter as
      we show that the feedback rate fixes the frequency of the periodic self
      pulsations. The interaction length of the crystal and the ratio between carrier
      and photon lifetimes tend to filter out high frequencies as they increase.
      Finally, the linewidth enhancement factor unlocks high frequencies as it
      increases. We conclude by providing a situation which leads to periodic solutions
      with higher frequencies using a set of realistic values of parameters.

PMID- 29195336
TI  - Control of electrical turbulence by periodic excitation of cardiac tissue.
AB  - Electrical turbulence in cardiac tissue is associated with arrhythmias such as
      life-threatening ventricular fibrillation. Recent experimental studies have shown
      that a sequence of low-energy electrical far-field pulses is able to terminate
      fibrillation more gently than a single high-energy pulse which causes severe side
      effects. During this low-energy antifibrillation pacing (LEAP), only tissue near
      sufficiently large conduction heterogeneities, such as large coronary arteries,
      is activated. In order to optimize LEAP, we performed extensive simulations of
      cardiac tissue perforated by blood vessels, employing two alternative cellular
      models that exhibit electrical turbulence at a similar length scale. Moreover,
      the scale of blood vessels in our two-dimensional simulations was chosen such
      that the threshold for single pulse defibrillation matches experimental values.
      For each of the 100 initial conditions, we tested different electrical field
      strengths, pulse shapes, numbers of pulses, and periods between the pulses. LEAP
      is successful for both models, albeit with substantial differences. One model
      exhibits a spectrum of chaotic activity featuring a narrow peak around a dominant
      frequency. In this case, the optimal period between low-energy pulses matches
      this frequency and LEAP greatly reduces the required energy for successful
      defibrillation. For pulses with larger energies, the system is perturbed such
      that underdrive pacing becomes advantageous. The spectrum of the second model
      features a broader peak, resulting in a less pronounced optimal pacing period and
      a decreased energy reduction. In both cases, pacing with five or six pulses which
      are separated by the dominant period maximizes the energy reduction.

PMID- 29195337
TI  - Multi-Gbit/s optical phase chaos communications using a time-delayed
      optoelectronic oscillator with a three-wave interferometer nonlinearity.
AB  - We propose a chaos communication scheme based on a chaotic optical phase carrier
      generated with an optoelectronic oscillator with nonlinear time-delay feedback.
      The system includes a dedicated non-local nonlinearity, which is a customized
      three-wave imbalanced interferometer. This particular feature increases the
      complexity of the chaotic waveform and thus the security of the transmitted
      information, as these interferometers are characterized by four independent
      parameters which are part of the secret key for the chaos encryption scheme. We
      first analyze the route to chaos in the system, and evidence a sequence of period
      doubling bifurcations from the steady-state to fully developed chaos. Then, in
      the chaotic regime, we study the synchronization between the emitter and the
      receiver, and achieve chaotic carrier cancellation with a signal-to-noise ratio
      up to 20 dB. We finally demonstrate error-free chaos communications at a data
      rate of 3 Gbit/s.

PMID- 29195338
TI  - Interactions and collisions of topological solitons in a semiconductor laser with
      optical injection and feedback.
AB  - We present experimental and numerical results about dynamical interactions of
      topological solitons in a semiconductor laser with coherent injection and
      feedback. We show different kind of interactions such as repulsion, annihilation,
      or formation of soliton bound states, depending on laser parameters. Collisions
      between single structures and bound states conserve momentum and charge.

PMID- 29195339
TI  - Quantization improves stabilization of dynamical systems with delayed feedback.
AB  - We show that an unstable scalar dynamical system with time-delayed feedback can
      be stabilized by quantizing the feedback. The discrete time model corresponds to
      a previously unrecognized case of the microchaotic map in which the fixed point
      is both locally and globally repelling. In the continuous-time model,
      stabilization by quantization is possible when the fixed point in the absence of
      feedback is an unstable node, and in the presence of feedback, it is an unstable
      focus (spiral). The results are illustrated with numerical simulation of the
      unstable Hayes equation. The solutions of the quantized Hayes equation take the
      form of oscillations in which the amplitude is a function of the size of the
      quantization step. If the quantization step is sufficiently small, the amplitude
      of the oscillations can be small enough to practically approximate the dynamics
      around a stable fixed point.

PMID- 29195340
TI  - Note: Wide-operating-range control for thermoelectric coolers.
AB  - A new algorithm for controlling the temperature of a thermoelectric cooler is
      proposed. Unlike a classic proportional-integral-derivative (PID) control, which
      computes the bias voltage from the temperature error, the proposed algorithm
      exploits the linear relation that exists between the cold side's temperature and
      the amount of heat that is removed per unit time. Since this control is based on
      an existing linear relation, it is insensitive to changes in the operating point
      that are instead crucial in classic PID control of a non-linear system.

PMID- 29195341
TI  - The effect of laser wavelength on the delay time of laser triggered vacuum
      switch.
AB  - The study on the influence of laser wavelength on the initial plasma properties
      of laser-triggered vacuum switch (LTVS) is not only beneficial to understanding
      the trigger mechanism but also to optimizing its design for miniaturization and
      generalization. In this paper, the one-dimensional heat conduction model of the
      target was developed and then the effect of laser wavelength on the depth of
      laser ablation and the quantity of initial plasma were investigated
      experimentally and theoretically with the laser absorption rate. The theoretical
      analysis was in good agreement with experimental measurement of the delay time of
      the LTVS. It is clear that the shorter the wavelength, the shorter the delay time
      will be after the LTVS is triggered.

PMID- 29195342
TI  - Grasping force hysteresis compensation of a piezoelectric-actuated wire clamp
      with a modified inverse Prandtl-Ishlinskii model.
AB  - This paper presents the grasping force hysteresis compensation of a piezoelectric
      actuated wire clamp with a modified hysteresis model. Considering dynamic
      characteristics of the wire clamp, a modified inverse Prandtl-Ishlinskii (MIPI)
      hysteresis model is developed to improve the hysteresis modeling accuracy. The
      proposed MIPI model is composed of a P-I model and a dynamic model which are
      connected in parallel. The proposed hysteresis model has the advantage of high
      modeling accuracy with a concise identification process, which means the step by
      step identification is not needed here. Experiments on grasping force hysteresis
      compensation with a feedforward controller are carried out based on the developed
      MIPI model. The grasping force error in steady state lies in +/-8.17 mN, while
      the maximum percentage and root mean square percentage of the grasping force
      error are 2.93% and 0.92%, respectively. The results show that the proposed
      hysteresis model is efficient and the wire clamp exhibits good performance with
      the feedforward controller. Therefore high frequency grasping operations can be
      realized based on the proposed MIPI hysteresis model.

PMID- 29195343
TI  - In situ ultraviolet shock radiance measurements using GaN-on-sapphire
      photodetectors.
AB  - Gallium nitride (GaN)-on-sapphire photodetectors are used to measure the
      ultraviolet (UV) radiance behind a shock wave in support of atmospheric entry
      sensing technologies. DC spectral response characterization of the GaN-based
      photodetectors shows a peak response around 365 nm with an UV/visible rejection
      of an order of magnitude. To conduct in situ measurements of UV shock-layer
      radiation, the GaN-based photodetectors were installed, without protective
      packaging, in the test section of a shock tube. The measured UV radiation, in
      terms of incident optical power on the photodetectors, is in excellent agreement
      with average UV radiation measured by the shock tube facility spectrometers.
      Furthermore, the device response after being subjected to the shock wave is
      unaltered, suggesting that the GaN-based material platform is suitable for
      implementation in aerospace and other harsh environment sensing applications.

PMID- 29195344
TI  - True randomness from an incoherent source.
AB  - Quantum random number generators (QRNGs) harness the intrinsic randomness in
      measurement processes: the measurement outputs are truly random, given the input
      state is a superposition of the eigenstates of the measurement operators. In the
      case of trusted devices, true randomness could be generated from a mixed state
      rho so long as the system entangled with rho is well protected. We propose a
      random number generation scheme based on measuring the quadrature fluctuations of
      a single mode thermal state using an optical homodyne detector. By mixing the
      output of a broadband amplified spontaneous emission (ASE) source with a single
      mode local oscillator (LO) at a beam splitter and performing differential photo
      detection, we can selectively detect the quadrature fluctuation of a single mode
      output of the ASE source, thanks to the filtering function of the LO.
      Experimentally, a quadrature variance about three orders of magnitude larger than
      the vacuum noise has been observed, suggesting this scheme can tolerate much
      higher detector noise in comparison with QRNGs based on measuring the vacuum
      noise. The high quality of this entropy source is evidenced by the small
      correlation coefficients of the acquired data. A Toeplitz-hashing extractor is
      applied to generate unbiased random bits from the Gaussian distributed raw data,
      achieving an efficiency of 5.12 bits per sample. The output of the Toeplitz
      extractor successfully passes all the NIST statistical tests for random numbers.

PMID- 29195345
TI  - Application of surface coil in nuclear magnetic resonance studies of physical
      properties of quasi-2D materials.
AB  - We conduct a comprehensive set of tests of performance of surface coils used for
      nuclear magnetic resonance (NMR) study of quasi-2-dimensional samples. We report
      115In and 31P NMR measurements on InP, semi-conducting thin substrate samples.
      Surface coils of both zig-zag meander-line and concentric spiral geometries were
      used. We compare reception sensitivity and signal-to-noise ratio of the NMR
      signal obtained by using surface-type coils to that obtained by standard solenoid
      type coils. As expected, we find that surface-type coils provide better
      sensitivity for NMR study of thin film samples. Moreover, we compare the
      reception sensitivity of different types of the surface coils. We identify the
      optimal geometry of the surface coils for a given application and/or direction of
      the applied magnetic field.

PMID- 29195346
TI  - Experimental setup for the growth of solid crystals of inert gases for particle
      detection.
AB  - Low energy threshold detectors are necessary in many frontier fields of the
      experimental physics. In this work, we present a novel detection approach based
      on pure or doped matrices of inert gases solidified at cryogenic temperatures.
      The small energy release of the incident particle can be transferred directly (in
      pure crystals) or through a laser-driven ionization (in doped materials) to the
      electrons of the medium that are then converted into free electrons. The charge
      collection process of the electrons that consists in their drift within the
      crystal and their extraction through the solid-vacuum interface gives rise to an
      electric signal that we exploit for preliminary tests of charge collection and
      crystal quality. Such tests are carried out in different matrices of neon and
      methane using an UV-assisted apparatus for electron injection in crystals.

PMID- 29195347
TI  - Technique for insulated and non-insulated metal liner X-pinch radiography on a 1
      MA pulsed power machine.
AB  - Broadband, high resolution X-pinch radiography has been demonstrated as a method
      to view the instability induced small scale structure that develops in near solid
      density regions of both insulated and non-insulated cylindrical metallic liners.
      In experiments carried out on a 1-1.2 MA 100-200 ns rise time pulsed power
      generator, MUm scale features were imaged in initially 16 MUm thick Al foil
      cylindrical liners. Better resolution and contrast were obtained using an X-ray
      sensitive film than with image plate detectors because of the properties of the X
      pinch X-ray source. We also discuss configuration variations that were made to
      the simple cylindrical liner geometry that appeared to maintain validity of the
      small-scale structure measurements while improving measurement quality.

PMID- 29195348
TI  - Simultaneous measurement of temperature, stress, and electric field in GaN HEMTs
      with micro-Raman spectroscopy.
AB  - As semiconductor devices based on silicon reach their intrinsic material limits,
      compound semiconductors, such as gallium nitride (GaN), are gaining increasing
      interest for high performance, solid-state transistor applications.
      Unfortunately, higher voltage, current, and/or power levels in GaN high electron
      mobility transistors (HEMTs) often result in elevated device temperatures,
      degraded performance, and shorter lifetimes. Although micro-Raman spectroscopy
      has become one of the most popular techniques for measuring localized temperature
      rise in GaN HEMTs for reliability assessment, decoupling the effects of
      temperature, mechanical stress, and electric field on the optical phonon
      frequencies measured by micro-Raman spectroscopy is challenging. In this work, we
      demonstrate the simultaneous measurement of temperature rise, inverse
      piezoelectric stress, thermoelastic stress, and vertical electric field via micro
      Raman spectroscopy from the shifts of the E2 (high), A1 longitudinal optical
      (LO), and E2 (low) optical phonon frequencies in wurtzite GaN. We also validate
      experimentally that the pinched OFF state as the unpowered reference accurately
      measures the temperature rise by removing the effect of the vertical electric
      field on the Raman spectrum and that the vertical electric field is approximately
      the same whether the channel is open or closed. Our experimental results are in
      good quantitative agreement with a 3D electro-thermo-mechanical model of the HEMT
      we tested and indicate that the GaN buffer acts as a semi-insulating, p-type
      material due to the presence of deep acceptors in the lower half of the bandgap.
      This implementation of micro-Raman spectroscopy offers an exciting opportunity to
      simultaneously probe thermal, mechanical, and electrical phenomena in
      semiconductor devices under bias, providing unique insight into the complex
      physics that describes device behavior and reliability. Although GaN HEMTs have
      been specifically used in this study to demonstrate its viability, this technique
      is applicable to any solid-state material with a suitable Raman response and will
      likely enable new measurement capabilities in a wide variety of scientific and
      engineering applications.

PMID- 29195349
TI  - Comparison of cryogenic low-pass filters.
AB  - Low-temperature electronic transport measurements with high energy resolution
      require both effective low-pass filtering of high-frequency input noise and an
      optimized thermalization of the electronic system of the experiment. In recent
      years, elaborate filter designs have been developed for cryogenic low-level
      measurements, driven by the growing interest in fundamental quantum-physical
      phenomena at energy scales corresponding to temperatures in the few millikelvin
      regime. However, a single filter concept is often insufficient to thermalize the
      electronic system to the cryogenic bath and eliminate spurious high frequency
      noise. Moreover, the available concepts often provide inadequate filtering to
      operate at temperatures below 10 mK, which are routinely available now in
      dilution cryogenic systems. Herein we provide a comprehensive analysis of
      commonly used filter types, introduce a novel compact filter type based on
      ferrite compounds optimized for the frequency range above 20 GHz, and develop an
      improved filtering scheme providing adaptable broad-band low-pass characteristic
      for cryogenic low-level and quantum measurement applications at temperatures down
      to few millikelvin.

PMID- 29195350
TI  - Coincidence velocity map imaging using Tpx3Cam, a time stamping optical camera
      with 1.5 ns timing resolution.
AB  - We demonstrate a coincidence velocity map imaging apparatus equipped with a novel
      time-stamping fast optical camera, Tpx3Cam, whose high sensitivity and nanosecond
      timing resolution allow for simultaneous position and time-of-flight detection.
      This single detector design is simple, flexible, and capable of highly
      differential measurements. We show detailed characterization of the camera and
      its application in strong field ionization experiments.

PMID- 29195351
TI  - OMNY PIN-A versatile sample holder for tomographic measurements at room and
      cryogenic temperatures.
AB  - Nowadays ptychographic tomography in the hard x-ray regime, i.e., at energies
      above about 2 keV, is a well-established measurement technique. At the Paul
      Scherrer Institut, currently two instruments are available: one is measuring at
      room temperature and atmospheric pressure, and the other, the so-called OMNY
      (tOMography Nano crYo) instrument, is operating at ultra-high vacuum and offering
      cryogenic sample temperatures down to 10 K. In this manuscript, we present the
      sample mounts that were developed for these instruments. Aside from excellent
      mechanical stability and thermal conductivity, they also offer highly
      reproducible mounting. Various types were developed for different kinds of
      samples and are presented in detail, including examples of how specimens can be
      mounted on these holders. We also show the first hard x-ray ptychographic
      tomography measurements of high-pressure frozen biological samples, in the
      present case Chlamydomonas cells, the related sample pins and preparation steps.
      For completeness, we present accessories such as transportation containers for
      both room temperature and cryogenic samples and a gripper mechanism for automatic
      sample changing. The sample mounts are not limited to x-ray tomography or hard x
      ray energies, and we believe that they can be very useful for other
      instrumentation projects.

PMID- 29195352
TI  - Reaction-time-resolved measurements of laser-induced fluorescence in a shock tube
      with a single laser pulse.
AB  - Shock tubes allow for the study of ultra-fast gas-phase reactions on the
      microsecond time scale. Because the repetition rate of the experiments is low, it
      is crucial to gain as much information as possible from each individual
      measurement. While reaction-time-resolved species concentration and temperature
      measurements with fast absorption methods are established, conventional laser
      induced fluorescence (LIF) measurements with pulsed lasers provide data only at a
      single reaction time. Therefore, fluorescence methods have rarely been used in
      shock-tube diagnostics. In this paper, a novel experimental concept is presented
      that allows reaction-time-resolved LIF measurements with one single laser pulse
      using a test section that is equipped with several optical ports. After the
      passage of the shock wave, the reactive mixture is excited along the center of
      the tube with a 266-nm laser beam directed through a window in the end wall of
      the shock tube. The emitted LIF signal is collected through elongated sidewall
      windows and focused onto the entrance slit of an imaging spectrometer coupled to
      an intensified CCD camera. The one-dimensional spatial resolution of the
      measurement translates into a reaction-time-resolved measurement while the
      species information can be gained from the spectral axis of the detected two
      dimensional image. Anisole pyrolysis was selected as the benchmark reaction to
      demonstrate the new apparatus.

PMID- 29195353
TI  - An optically referenced inclinometer with sub-microradian repeatability.
AB  - A pendulum inclinometer has been built and tested, suitable for measuring the
      deflection of the gravitational vertical to an accuracy of 1 MUrad. The design is
      based on measuring the differential capacitance between a pendulum bob and two
      closely spaced parallel electrodes. Two independent pendulums are oriented
      orthogonally to measure both coordinates. A collimated optical beam is stably
      attached to the inclinometer pair and provides a means for making stellar
      measurements relative to the gravitational vertical. For optimum performance, the
      inclinometer is operated at its null position by supporting the entire assembly
      on a rigid tilting plate. Good repeatability is a key feature of this
      inclinometer.

PMID- 29195354
TI  - Phase noise measurements with a cryogenic power-splitter to minimize the cross
      spectral collapse effect.
AB  - The cross-spectrum noise measurement technique enables enhanced resolution of
      spectral measurements. However, it has disadvantages, namely, increased
      complexity, inability of making real-time measurements, and bias due to the
      "cross-spectral collapse" (CSC) effect. The CSC can occur when the spectral
      density of a random process under investigation approaches the thermal noise of
      the power splitter. This effect can severely bias results due to a differential
      measurement between the investigated noise and the anti-correlated (phase
      inverted) noise of the power splitter. In this paper, we report an accurate
      measurement of the phase noise of a thermally limited electronic oscillator
      operating at room temperature (300 K) without significant CSC bias. We mitigated
      the problem by cooling the power splitter to liquid helium temperature (4 K). We
      quantify errors of greater than 1 dB that occur when the thermal noise of the
      oscillator at room temperature is measured with the power splitter at
      temperatures above 77 K.

PMID- 29195355
TI  - Aspheric optical surface profiling based on laser scanning and auto-collimation.
AB  - Nowadays the utilization of aspheric lenses has become more and more popular,
      enabling highly increased degree of freedom for optical design and simultaneously
      improving the performance of optical systems. Fast and accurate surface profiling
      of these aspheric components is a real demand in characterization and
      optimization of the optical systems. In this paper, a novel and simple surface
      profiler instrument is designed and developed to fulfill the ever increasing need
      of testing the axially symmetric aspheric surface. The proposed instrument is
      implemented based on a unique mapping between the position and rotation angle of
      the reflective mirror in optical path and the coordinate of reflection point on
      the surface during rapid laser beam scanning. High accuracy of the proposed
      surface profiling method is ensured by a high-resolution grating guide rail,
      indexing plate, and position sensitive detector based on laser auto-collimation
      and beam center-fitting. Testing the meridian line of both convex and concave
      surfaces has been experimentally demonstrated using the developed instrument. In
      comparison to tested results from conventional image measuring instruments and
      coordinate measuring machines, coefficient of determination better than 0.999 99
      and RMS less than 1.5 MUm have been achieved, which validates the feasibility of
      this method. Analysis on the systematic error is beneficial to further improve
      its measurement accuracy. The presented instrument-essentially builds on the
      geometrical optics technique-provides a powerful tool to measure the aspheric
      surfaces quickly and accurately with stable structure and simple algorithm.

PMID- 29195356
TI  - A new instrument of VUV laser desorption/ionization mass spectrometry imaging
      with micrometer spatial resolution and low level of molecular fragmentation.
AB  - Mass spectrometry imaging (MSI) has important applications in material research,
      biology, and medicine. The MSI method based on UV laser desorption/ionization
      (UVLDI) can obtain images of intact samples, but has a high level of molecular
      fragmentation. In this work, we report a new MSI instrument that uses a VUV laser
      (125.3 nm) as a desorption/ionization source to exploit its advantages of high
      single photon energy and small focus size. The new instrument was tested by the
      mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass
      spectrometric images of a fly brain section. For the tested samples, the VUVDI
      method offers lower levels of molecular fragmentations and higher sensitivities
      than those of the UVLDI method and second ion mass spectrometry imaging method
      using a Bi3+ beam. The ablation crater produced by the focused VUV laser on a
      quartz plate has an area of 10 MUm2. The VUV laser is prepared based on the four
      wave mixing method using three collimated laser beams and a heated Hg cell.

PMID- 29195357
TI  - Calibration of imaging plate detectors to mono-energetic protons in the range 1
      200 MeV.
AB  - Responses of Fuji Imaging Plates (IPs) to proton have been measured in the range
      1-200 MeV. Mono-energetic protons were produced with the 15 MV ALTO-Tandem
      accelerator of the Institute of Nuclear Physics (Orsay, France) and, at higher
      energies, with the 200-MeV isochronous cyclotron of the Institut Curie-Centre de
      Protontherapie d'Orsay (Orsay, France). The experimental setups are described and
      the measured photo-stimulated luminescence responses for MS, SR, and TR IPs are
      presented and compared to existing data. For the interpretation of the results, a
      sensitivity model based on the Monte Carlo GEANT4 code has been developed. It
      enables the calculation of the response functions in a large energy range, from
      0.1 to 200 MeV. Finally, we show that our model reproduces accurately the
      response of more complex detectors, i.e., stack of high-Z filters and IPs, which
      could be of great interest for diagnostics of Petawatt laser accelerated
      particles.

PMID- 29195358
TI  - Novel single-cell mega-size chambers for electrochemical etching of panorama
      position-sensitive polycarbonate ion image detectors.
AB  - A novel development is made here by inventing panorama single-cell mega-size
      electrochemical etching (MS-ECE) chamber systems for processing panorama position
      sensitive mega-size polycarbonate ion image detectors (MS-PCIDs) of potential for
      many neutron and ion detection applications in particular hydrogen ions or proton
      tracks and images detected for the first time in polycarbonates in this study.
      The MS-PCID is simply a large polycarbonate sheet of a desired size. The single
      cell MS-ECE invented consists of two large equally sized transparent Plexiglas
      sheets as chamber walls holding a MS-PCID and the ECE chamber components tightly
      together. One wall has a large flat stainless steel electrode (dry cell) attached
      to it which is directly in contact with the MS-PCID and the other wall has a rod
      electrode with two holes to facilitate feeding and draining out the etching
      solution from the wet cell. A silicon rubber washer plays the role of the wet
      cell to hold the etchant and the electrical insulator to isolate the dry cell
      from the wet cell. A simple 50 Hz-HV home-made generator provides an adequate
      field strength through the two electrodes across the MS-ECE chamber. Two panorama
      single-cell MS-ECE chamber systems (circular and rectangular shapes) constructed
      were efficiently applied to processing the MS-PCIDs for 4pi ion emission image
      detection of different gases in particular hydrogen ions or protons in a 3.5 kJ
      plasma focus device (PFD as uniquely observed by the unaided eyes). The panorama
      MS-PCID/MS-ECE image detection systems invented are novel with high potential for
      many applications in particular as applied to 4pi panorama ion emission angular
      distribution image detection studies in PFD space, some results of which are
      presented and discussed.

PMID- 29195359
TI  - Improved accuracy of capacitive sensor-based micro-angle measurement with angular
      to-linear displacement conversion.
AB  - This paper presents a capacitive sensor-based micro-angle measurement (CSMAM)
      method that uses an angular-to-linear displacement conversion to achieve high
      accuracy. The principal and secondary error components of CSMAMs are modeled and
      analyzed to reveal their impacts on the measurement accuracy. The theoretical
      accuracies of six types of commonly used CSMAMs are analyzed to determine the
      optimum configuration of capacitive sensors for 1D and 2D micro-angle
      measurements. An angular-to-linear displacement conversion method with a linear
      motional stage and a hemisphere decoupler is used to eliminate the principal
      error of CSMAM. Experimental results indicate that the optimized CSMAM can
      achieve accuracies of 0.157 arc sec and 0.052 arc sec in the ranges of +/-900 arc
      sec and +/-300 arc sec, respectively, in the case that the effective length of
      the rotation arm is 100 mm and the linear displacement measurement accuracy of
      the capacitive sensor is 2 nm. These results can be used as a reference to
      further improve CSMAM designs and achieve high accuracy in a large measurement
      range, for use in a wide range of precision engineering applications including
      angle metrology, micro- and nano-radian angle generators, beam steering
      mechanisms, and high-performance precision stages.

PMID- 29195360
TI  - Biased four-point probe resistance.
AB  - The implications of switching the current polarity in a four-point probe
      resistance measurement are presented. We demonstrate that, during the inversion
      of the applied current, any change in the voltage V produced by a continuous drop
      of the sample temperature T will induce a bias in the temperature-dependent DC
      resistance. The analytical expression for the bias is deduced and written in
      terms of the variations of the measured voltages with respect to T and by the
      variations of T with respect to time t. Experimental data measured on a
      superconducting Nb thin film confirm that the bias of the normal-state resistance
      monotonically increases with the cooling rate dT/dt while keeping fixed dV/dT; on
      the other hand, the bias increases with dV/dT, reaching values up to 13% with
      respect to the unbiased resistance obtained at room temperature.

PMID- 29195361
TI  - Modular injector integrated linear apparatus with motion profile optimization for
      spatial atomic layer deposition.
AB  - A spatial atomic layer deposition apparatus integrated with a modular injector
      and a linear motor has been designed. It consists of four parts: a precursor
      delivery manifold, a modular injector, a reaction zone, and a driving unit. An
      injector with multi-layer structured channels is designed to help improve
      precursor distribution homogeneity. During the back and forth movement of the
      substrate at high speed, the inertial impact caused by jerk and sudden changes of
      acceleration will degrade the film deposition quality. Such residual vibration
      caused by inertial impact will aggravate the fluctuation of the gap distance
      between the injector and the substrate in the deposition process. Thus, an S
      curve motion profile is implemented to reduce the large inertial impact, and the
      maximum position error could be reduced by 84%. The microstructure of the film
      under the S-curve motion profile shows smaller root-mean-square and scanning
      voltage amplitude under an atomic force microscope, which verifies the
      effectiveness of the S-curve motion profile in reducing the residual vibration
      and stabilizing the gap distance between the injector and the substrate. The film
      deposition rate could reach 100 nm/min while maintaining good uniformity without
      obvious periodic patterns on the surface.

PMID- 29195362
TI  - A novel optical rotary encoder with eccentricity self-detection ability.
AB  - Eccentricity error is the main error source of optical rotary encoders. Real-time
      detection and compensation of the eccentricity error is an effective way of
      improving the accuracy of rotary optical encoders. In this paper, a novel rotary
      optical encoder is presented to realize eccentricity self-detection. The proposed
      encoder adopts a spider-web-patterned scale grating as a measuring standard which
      is scanned by a dual-head scanning unit. Two scanning heads of the dual-head
      scanning unit, which are arranged orthogonally, have the function of scanning the
      periodic pattern of the scale grating along the angular and radial directions,
      respectively. By this means, synchronous measurement of angular and radial
      displacements of the scale grating is realized. This paper gives the details of
      the operating principle of the rotary optical encoder, developing and testing
      work of a prototype. The eccentricity self-detection result agrees well with the
      result measured by an optical microscope. The experimental result preliminarily
      proves the feasibility and effectiveness of the proposed optical encoder.

PMID- 29195363
TI  - Hyperspectral imaging with deformable gratings fabricated with metal-elastomer
      nanocomposites.
AB  - We report the fabrication and characterization of a simple and compact
      hyperspectral imaging setup based on a stretchable diffraction grating made with
      a metal-polymer nanocomposite. The nanocomposite is produced by implanting Ag
      clusters in a poly(dimethylsiloxane) film by supersonic cluster beam
      implantation. The deformable grating has curved grooves and is imposed on a
      concave cylindrical surface, thus obtaining optical power in two orthogonal
      directions. Both diffractive and optical powers are obtained by reflection, thus
      realizing a diffractive-catoptric optical device. This makes it easier to
      minimize aberrations. We prove that, despite the extended spectral range and the
      simplified optical scheme, it is actually possible to work with a traditional CCD
      sensor and achieve a good spectral and spatial resolution.

PMID- 29195364
TI  - Injector design for liner-on-target gas-puff experiments.
AB  - We present the design of a gas-puff injector for liner-on-target experiments. The
      injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and
      an on-axis plasma gun that delivers an ionized deuterium target. The annular
      supersonic nozzle injector has been studied using Computational Fluid Dynamics
      (CFD) simulations to produce a highly collimated (M > 5), ~1 cm radius gas
      profile that satisfies the theoretical requirement for best performance on ~1-MA
      current generators. The CFD simulations allowed us to study output density
      profiles as a function of the nozzle shape, gas pressure, and gas composition. We
      have performed line-integrated density measurements using a continuous wave (CW)
      He-Ne laser to characterize the liner gas density. The measurements agree well
      with the CFD values. We have used a simple snowplow model to study the plasma
      sheath acceleration in a coaxial plasma gun to help us properly design the target
      injector.

PMID- 29195365
TI  - A burn depth detection system based on near infrared spectroscopy and ensemble
      learning.
AB  - Near infrared (NIR) spectroscopy can effectively detect the changes in the burned
      tissue. However, due to the complex relationship between the spectral signals and
      the burn depth, simple methods of data analysis are difficult to solve this
      problem effectively. Therefore, in this paper, a machine learning method is
      introduced into the NIR spectral signal analysis, which is used to establish the
      relationship between NIR spectral signals and burn depth. First, based on the
      intensity of the spectral signal and the diffuse reflection theory, the optical
      properties that can reflect the change of burned tissue are extracted. And then
      the chained-agent genetic algorithm (CAGA) optimized support vector regression
      (SVR) is applied to establish a regression model between the optical property
      parameters and burn depth. Finally, the porcine model was used for verification.
      The experimental results demonstrate that the proposed CAGA-SVR integrated
      inversion model with optical properties can perform accurate inversion of burn
      depth and provide a reference for doctors.

PMID- 29195366
TI  - Design and experiment of a small-scale walking robot employing stick-slip motion
      principle.
AB  - We describe the design and control of a four legged walking robot, 45 g in weight
      and 130 mm * 105 mm * 25 mm in size. Each leg consists of two piezoelectric
      bimorph actuators that are bonded at the free end by a flexure and an end
      effector. The robot generates stick-slip locomotion when applying sawtooth shaped
      voltage signals. Friction between legs and a contact surface is analyzed by using
      the Coulomb friction model. Locomotion characteristics are measured in several
      experiments. The robot was driven with frequencies up to 75 Hz, and a maximum
      velocity of 65 mm/s was obtained at two frequencies: 45 Hz with 190 Vpp driving
      voltage and 60 Hz with 170 Vpp driving voltage, respectively.

PMID- 29195367
TI  - A versatile apparatus for two-dimensional atomtronic quantum simulation.
AB  - We report on the implementation of a novel optical setup for generating high
      resolution customizable potentials to address ultracold bosonic atoms in two
      dimensions. Two key features are developed for this purpose. The customizable
      potential is produced with a direct image of a spatial light modulator, conducted
      with an in-vacuum imaging system of high numerical aperture. Custom potentials
      are drawn over an area of 600*400 MUm with a resolution of 0.9 MUm. The second
      development is a two-dimensional planar trap for atoms with an aspect ratio of
      900 and spatial extent of Rayleigh range 1.6 * 1.6 mm, providing near-ballistic
      in-planar movement. We characterize the setup and present a brief catalog of
      experiments to highlight the versatility of the system.

PMID- 29195368
TI  - Simple measuring rod method for the coaxiality of serial holes.
AB  - Aiming at the rapid coaxiality measurement of serial hole part with a small
      diameter, a coaxiality measuring rod for each layer hole with a single LDS (laser
      displacement sensor) is proposed. This method does not require the rotation angle
      information of the rod, and the coaxiality of serial holes can be calculated from
      the measured values of LDSs after randomly rotating the measuring rod several
      times. With the mathematical model of the coaxiality measuring rod, each factor
      affecting the accuracy of coaxiality measurement is analyzed by simulation, and
      the installation accuracy requirements of the measuring rod and LDSs are
      presented. In the tolerance of a certain installation error of the measuring rod,
      the relative center of the hole is calculated by setting the over-determined
      nonlinear equations of the fitting circles of the multi-layer holes. In
      experiment, coaxiality measurement accuracy is realized by a 16 MUm precision
      LDS, and the validity of the measurement method is verified. The manufacture and
      measurement requirements of the coaxiality measuring rod are low, by changing the
      position of LDSs in the measuring rod, the serial holes with different sizes and
      numbers can be measured. The rapid coaxiality measurement of parts can be easily
      implemented in industrial sites.

PMID- 29195370
TI  - Note: Retrofitting an analog spectrometer for high resolving power in NUV-NIR.
AB  - We demonstrate how an older spectrometer designed for photographic films can be
      efficiently retrofitted with a narrow laser-cut slit and a modern MUm-pixel-size
      imaging CMOS camera, yielding sub-pm resolution in the broad near ultraviolet to
      near infrared (NUV-NIR) spectral range. Resolving power approaching 106 is
      achieved. Such digital retrofitting of an analog instrument is practical for
      research and teaching laboratories.

PMID- 29195371
TI  - CAT-ACT-A new highly versatile x-ray spectroscopy beamline for catalysis and
      radionuclide science at the KIT synchrotron light facility ANKA.
AB  - CAT-ACT-the hard X-ray beamline for CATalysis and ACTinide/radionuclide research
      at the KIT synchrotron radiation facility ANKA-is dedicated to X-ray
      spectroscopy, including "flux hungry" photon-in/photon-out and correlative
      techniques and combines state-of-the-art optics with a unique infrastructure for
      radionuclide and catalysis research. Measurements can be performed at photon
      energies varying between 3.4 keV and 55 keV, thus encompassing the actinide M-
      and L-edge or potassium K-edge up to the K-edges of the lanthanide series such as
      cerium. Well-established X-ray absorption fine structure spectroscopy in
      transmission and fluorescence detection modes is available in combination with
      high energy-resolution X-ray emission spectroscopy or X-ray diffraction
      techniques. The modular beamline design with two alternately operated in-line
      experimental stations enables sufficient flexibility to adapt sample environments
      and detection systems to many scientific challenges. The ACT experimental station
      focuses on various aspects of nuclear waste disposal within the mission of the
      Helmholtz association to contribute to the solution of one of the greatest
      scientific and social challenges of our time-the safe disposal of heat producing,
      highly radioactive waste forms from nuclear energy production. It augments
      present capabilities at the INE-Beamline by increasing the flux and extending the
      energy range into the hard X-ray regime. The CAT experimental station focuses on
      catalytic materials, e.g., for energy-related and exhaust gas catalysis.
      Characterization of catalytically active materials under realistic reaction
      conditions and the development of in situ and operando cells for sample
      environments close to industrial reactors are essential aspects at CAT.

PMID- 29195372
TI  - The nanopore mass spectrometer.
AB  - We report the design of a mass spectrometer featuring an ion source that delivers
      ions directly into high vacuum from liquid inside a capillary with a sub
      micrometer-diameter tip. The surface tension of water and formamide is sufficient
      to maintain a stable interface with high vacuum at the tip, and the gas load from
      the interface is negligible, even during electrospray. These conditions lifted
      the usual requirement of a differentially pumped system. The absence of a
      background gas also opened up the possibility of designing ion optics to collect
      and focus ions in order to achieve high overall transmission and detection
      efficiencies. We describe the operation and performance of the instrument and
      present mass spectra from solutions of salt ions and DNA bases in formamide and
      salt ions in water. The spectra show singly charged solute ions clustered with a
      small number of solvent molecules.

PMID- 29195373
TI  - Air sampling unit for breath analyzers.
AB  - The paper presents a portable breath sampling unit (BSU) for human breath
      analyzers. The developed unit can be used to probe air from the upper airway and
      alveolar for clinical and science studies. The BSU is able to operate as a
      patient interface device for most types of breath analyzers. Its main task is to
      separate and to collect the selected phases of the exhaled air. To monitor the so
      called I, II, or III phase and to identify the airflow from the upper and lower
      parts of the human respiratory system, the unit performs measurements of the
      exhaled CO2 (ECO2) in the concentration range of 0%-20% (0-150 mm Hg). It can
      work in both on-line and off-line modes according to American Thoracic
      Society/European Respiratory Society standards. A Tedlar bag with a volume of 5
      dm3 is mounted as a BSU sample container. This volume allows us to collect ca. 1
      25 selected breath phases. At the user panel, each step of the unit operation is
      visualized by LED indicators. This helps us to regulate the natural breathing
      cycle of the patient. There is also an operator's panel to ensure monitoring and
      configuration setup of the unit parameters. The operation of the breath sampling
      unit was preliminarily verified using the gas chromatography/mass spectrometry
      (GC/MS) laboratory setup. At this setup, volatile organic compounds were
      extracted by solid phase microextraction. The tests were performed by the
      comparison of GC/MS signals from both exhaled nitric oxide and isoprene analyses
      for three breath phases. The functionality of the unit was proven because there
      was an observed increase in the signal level in the case of the III phase
      (approximately 40%). The described work made it possible to construct a prototype
      of a very efficient breath sampling unit dedicated to breath sample analyzers.

PMID- 29195374
TI  - Huddle test measurement of a near Johnson noise limited geophone.
AB  - In this paper, the sensor noise of two geophone configurations (L-22D and L-4C
      geophones from Sercel with custom built amplifiers) was measured by performing
      two huddle tests. It is shown that the accuracy of the results can be
      significantly improved by performing the huddle test in a seismically quiet
      environment and by using a large number of reference sensors to remove the
      seismic foreground signal from the data. Using these two techniques, the measured
      sensor noise of the two geophone configurations matched the calculated
      predictions remarkably well in the bandwidth of interest (0.01 Hz-100 Hz). Low
      noise operational amplifiers OPA188 were utilized to amplify the L-4C geophone to
      give a sensor that was characterized to be near Johnson noise limited in the
      bandwidth of interest with a noise value of 10-11 m/Hz at 1 Hz.

PMID- 29195375
TI  - Sensor fault diagnosis of aero-engine based on divided flight status.
AB  - Fault diagnosis and safety analysis of an aero-engine have attracted more and
      more attention in modern society, whose safety directly affects the flight safety
      of an aircraft. In this paper, the problem concerning sensor fault diagnosis is
      investigated for an aero-engine during the whole flight process. Considering that
      the aero-engine is always working in different status through the whole flight
      process, a flight status division-based sensor fault diagnosis method is
      presented to improve fault diagnosis precision for the aero-engine. First, aero
      engine status is partitioned according to normal sensor data during the whole
      flight process through the clustering algorithm. Based on that, a diagnosis model
      is built for each status using the principal component analysis algorithm.
      Finally, the sensors are monitored using the built diagnosis models by
      identifying the aero-engine status. The simulation result illustrates the
      effectiveness of the proposed method.

PMID- 29195376
TI  - Measurement of contact angles at room temperature in high magnetic field.
AB  - The contact angle (CA) goniometer adaptable to a superconducting magnet was
      developed based on the sessile drop method. The goniometer mainly consisted of
      the sampling system, the supporting system, and the image acquisition system.
      Some improvements were taken to avoid the effects of the magnetic field (MF) on
      the CA measurement. As an example, the CAs of water on two substrates of silica
      and polymethyl methacrylate (PMMA) were measured using the goniometer. The
      results with and without a MF showed a good repeatability and reliability.
      Additionally, the MF was found to reduce the CA of water, which probably stemmed
      from the change of the surface tension in the MF. The CA goniometer will become
      an important tool which is used to study the wettability of liquids on a solid in
      the MF.

PMID- 29195377
TI  - Portable device for generation of ultra-pure water vapor feeds.
AB  - A portable device for the generation of co-feeds of water vapor has been
      designed, constructed, and evaluated for flexible use as an add-on component to
      laboratory chemical reactors. The vapor is formed by catalytic oxidation of
      hydrogen, which benefits the formation of well-controlled minute concentrations
      of ultra-pure water. Analysis of the effluent stream by on-line mass spectrometry
      and Fourier transform infrared spectroscopy confirms that water vapor can be,
      with high precision, generated both rapidly and steadily over extended periods in
      the range of 100 ppm to 3 vol. % (limited by safety considerations) using a total
      flow of 100 to 1500 ml/min at normal temperature and pressure. Further, the
      device has been used complementary to a commercial water evaporator and mixing
      system to span water concentrations up to 12 vol. %. Finally, an operando diffuse
      reflective infrared Fourier transform spectroscopic measurement of palladium
      catalysed methane oxidation in the absence and presence of up to 1.0 vol. % water
      has been carried out to demonstrate the applicability of the device for co
      feeding well-controlled low concentrations of water vapor to a common type of
      spectroscopic experiment. The possibilities of creating isotopically labeled
      water vapor as well as using tracer gases for dynamic experiments are discussed.

PMID- 29195378
TI  - Neutron and X-ray Tomography (NeXT) system for simultaneous, dual modality
      tomography.
AB  - Dual mode tomography using neutrons and X-rays offers the potential of improved
      estimation of the composition of a sample from the complementary interaction of
      the two probes with the sample. We have developed a simultaneous neutron and 90
      keV X-ray tomography system that is well suited to the study of porous media
      systems such as fuel cells, concrete, unconventional reservoir geologies,
      limestones, and other geological media. We present the characteristic performance
      of both the neutron and X-ray modalities. We illustrate the use of the
      simultaneous acquisition through improved phase identification in a concrete
      core.

PMID- 29195379
TI  - A tomography diagnostic in the visible spectrum to investigate turbulence and
      coherent modes in the linear plasma column Mistral.
AB  - In this paper, we describe a newly installed tomography diagnostic on the linear
      magnetized plasma device Mistral. The diagnostic is composed of 128 lines of
      sight covering a 20 cm diameter section and an acquisition rate up to 1 MHz. The
      measurements are done in the visible spectrum using silicon photomultiplier
      arrays that require a lower amplification voltage than photomultiplier tubes for
      similar gains and have a fast response. Tomographic reconstruction of a rotating
      plasma mode is shown to illustrate the capabilities of the diagnostic.

PMID- 29195380
TI  - Signal processing and analysis for copper layer thickness measurement within a
      large variation range in the CMP process.
AB  - In the copper (Cu) chemical mechanical planarization (CMP) process, accurate
      determination of a process reaching the end point is of great importance. Based
      on the eddy current technology, the in situ thickness measurement of the Cu layer
      is feasible. Previous research studies focus on the application of the eddy
      current method to the metal layer thickness measurement or endpoint detection. In
      this paper, an in situ measurement system, which is independently developed by
      using the eddy current method, is applied to the actual Cu CMP process. A series
      of experiments are done for further analyzing the dynamic response characteristic
      of the output signal within different thickness variation ranges. In this study,
      the voltage difference of the output signal is used to represent the thickness of
      the Cu layer, and we can extract the voltage difference variations from the
      output signal fast by using the proposed data processing algorithm. The results
      show that the voltage difference decreases as thickness decreases in the
      conventional measurement range and the sensitivity increases at the same time.
      However, it is also found that there exists a thickness threshold, and the
      correlation is negative, when the thickness is more than the threshold.
      Furthermore, it is possible that the in situ measurement system can be used
      within a larger Cu layer thickness variation range by creating two calibration
      tables.

PMID- 29195381
TI  - In situ calibration of neutron activation system on the large helical device.
AB  - In situ calibration of the neutron activation system on the Large Helical Device
      (LHD) was performed by using an intense 252Cf neutron source. To simulate a ring
      shaped neutron source, we installed a railway inside the LHD vacuum vessel and
      made a train loaded with the 252Cf source run along a typical magnetic axis
      position. Three activation capsules loaded with thirty pieces of indium foils
      stacked with total mass of approximately 18 g were prepared. Each capsule was
      irradiated over 15 h while the train was circulating. The activation response
      coefficient (9.4 +/- 1.2) * 10-8 of 115In(n, n')115mIn reaction obtained from the
      experiment is in good agreement with results from three-dimensional neutron
      transport calculations using the Monte Carlo neutron transport simulation code 6.
      The activation response coefficients of 2.45 MeV birth neutron and secondary 14.1
      MeV neutron from deuterium plasma were evaluated from the activation response
      coefficient obtained in this calibration experiment with results from three
      dimensional neutron calculations using the Monte Carlo neutron transport
      simulation code 6.

PMID- 29195382
TI  - A dynamic monitoring approach for the surface morphology evolution measurement of
      plasma facing components by means of speckle interferometry.
AB  - Plasma Facing Components (PFCs) in a magnetically confined fusion plasma device
      will be exposed to high heat load and particle fluxes, and it would cause PFCs'
      surface morphology to change due to material erosion and redeposition from plasma
      wall interactions. The state of PFCs' surface condition will seriously affect the
      performance of long-pulse or steady state plasma discharge in a tokamak; it will
      even constitute an enormous threat to the operation and the safety of fusion
      plasma devices. The PFCs' surface morphology evolution measurement could provide
      important information about PFCs' real-time status or damage situation and it
      would help to a better understanding of the plasma wall interaction process and
      mechanism. Meanwhile through monitoring the distribution of dust deposition in a
      tokamak and providing an upper limit on the amount of loose dust, the PFCs'
      surface morphology measurement could indirectly contribute to keep fusion
      operational limits and fusion device safety. Aiming at in situ dynamic monitoring
      PFCs' surface morphology evolution, a laboratory experimental platform DUT-SIEP
      (Dalian University of Technology-speckle interferometry experimental platform)
      based on the speckle interferometry technique has been constructed at Dalian
      University of Technology (DUT) in China. With directional specific designing and
      focusing on the real detection condition of EAST (Experimental Advanced
      Superconducting Tokamak), the DUT-SIEP could realize a variable measurement
      range, widely increased from 0.1 MUm to 300 MUm, with high spatial resolution (<1
      mm) and ultra-high time resolution (<2 s for EAST measuring conditions). Three
      main components of the DUT-SIEP are all integrated and synchronized by a time
      schedule control and data acquisition terminal and coupled with a three
      dimensional phase unwrapping algorithm, the surface morphology information of
      target samples can be obtained and reconstructed in real-time. A local surface
      morphology of the real divertor tiles adopted from EAST has been measured, and
      the feasibility and reliability of this new experimental platform have been
      demonstrated.

PMID- 29195383
TI  - A sensor for vector electric field measurements through a nonlinear anisotropic
      optical crystal.
AB  - Electrical applications require the development of electric field sensors that
      can reproduce vector electric field waveforms with a very large spectral width
      ranging from 50 Hz to at least 70 MHz. This makes it possible to measure both the
      normal operation modes of electrical components and abnormal behaviors such as
      the corona emission and partial discharges. In this work, we aim to develop a
      fully dielectric sensor capable of measuring two components of the electric field
      using a wide class of optical crystals including anisotropic ones, whereas most
      of the efforts in this field have been devoted to isotropic crystals. We report
      the results of the measurements performed at 50 Hz and with a lightning impulse,
      to validate the sensor.

PMID- 29195384
TI  - THz-pump and X-ray-probe sources based on an electron linac.
AB  - We describe a compact THz-pump and X-ray-probe beamline, based on an electron
      linac, for ultrafast time-resolved diffraction applications. Two high-energy
      electron (gamma > 50) bunches, 5 ns apart, impinge upon a single-foil or
      multifoil radiator and generate THz radiation and X-rays simultaneously. The THz
      pulse from the first bunch is synchronized to the X-ray beam of the second bunch
      by using an adjustable optical delay of a THz pulse. The peak power of THz
      radiation from the multifoil radiator is estimated to be 0.14 GW for a 200 pC
      well-optimized electron bunch. GEANT4 simulations show that a carbon foil with a
      thickness of 0.5-1.0 mm has the highest yield of 10-20 keV hard X-rays for a 25
      MeV beam, which is approximately 103 photons/(keV pC-electrons) within a few
      degrees of the polar angle. A carbon multifoil radiator with 35 foils (25 MUm
      thick each) can generate close to 103 hard X-rays/(keV pC-electrons) within a 2
      degrees  acceptance angle. With 200 pC charge and a 100 Hz repetition rate, we
      can generate 107 X-rays per 1 keV energy bin per second or 105 X-rays per 1 keV
      energy bin per pulse. The longitudinal time profile of an X-ray pulse ranges from
      400 to 600 fs depending on the acceptance angle. The broadening of the time
      duration of an X-ray pulse is observed owing to its diverging effect. A double
      crystal monochromator will be used to select and transport the desired X-rays to
      the sample. The heating of the radiators by an electron beam is negligible
      because of the low beam current.

PMID- 29195385
TI  - Design and numerical simulation on an auto-cumulative flowmeter in horizontal oil
      water two-phase flow.
AB  - In order to accurately measure the flow rate under the low yield horizontal well
      conditions, an auto-cumulative flowmeter (ACF) was proposed. Using the proposed
      flowmeter, the oil flow rate in horizontal oil-water two-phase segregated flow
      can be finely extracted. The computational fluid dynamics software Fluent was
      used to simulate the fluid of the ACF in oil-water two-phase flow. In order to
      calibrate the simulation measurement of the ACF, a novel oil flow rate
      measurement method was further proposed. The models of the ACF were simulated to
      obtain and calibrate the oil flow rate under different total flow rates and oil
      cuts. Using the finite-element method, the structure of the seven conductance
      probes in the ACF was simulated. The response values for the probes of the ACF
      under the conditions of oil-water segregated flow were obtained. The experiments
      for oil-water segregated flow under different heights of the oil accumulation in
      horizontal oil-water two-phase flow were carried out to calibrate the ACF. The
      validity of the oil flow rate measurement in horizontal oil-water two-phase flow
      was verified by simulation and experimental results.

PMID- 29195386
TI  - Fitting a defect non-linear model with or without prior, distinguishing nuclear
      reaction products as an example.
AB  - Fitting a parametrized function to data is important for many researchers and
      scientists. If the model is non-linear and/or defect, it is not trivial to do
      correctly and to include an adequate uncertainty analysis. This work presents how
      the Levenberg-Marquardt algorithm for non-linear generalized least squares
      fitting can be used with a prior distribution for the parameters and how it can
      be combined with Gaussian processes to treat model defects. An example, where
      three peaks in a histogram are to be distinguished, is carefully studied. In
      particular, the probability r1 for a nuclear reaction to end up in one out of two
      overlapping peaks is studied. Synthetic data are used to investigate effects of
      linearizations and other assumptions. For perfect Gaussian peaks, it is seen that
      the estimated parameters are distributed close to the truth with good covariance
      estimates. This assumes that the method is applied correctly; for example, prior
      knowledge should be implemented using a prior distribution and not by assuming
      that some parameters are perfectly known (if they are not). It is also important
      to update the data covariance matrix using the fit if the uncertainties depend on
      the expected value of the data (e.g., for Poisson counting statistics or relative
      uncertainties). If a model defect is added to the peaks, such that their shape is
      unknown, a fit which assumes perfect Gaussian peaks becomes unable to reproduce
      the data, and the results for r1 become biased. It is, however, seen that it is
      possible to treat the model defect with a Gaussian process with a covariance
      function tailored for the situation, with hyper-parameters determined by leave
      one-out cross validation. The resulting estimates for r1 are virtually unbiased,
      and the uncertainty estimates agree very well with the underlying uncertainty.

PMID- 29195387
TI  - An in situ simultaneous measurement system combining photoelasticity and caustics
      methods for blast-induced dynamic fracture.
AB  - Photoelasticity and caustics methods are extensively used in the history of
      dynamic fracture mechanics. However, there is little work for the combination of
      them in the same experiment associated with high loading rate in extreme
      conditions. In the present work, it is the first time to build a simultaneous
      measurement system which can use photoelasticity and caustics methods at the same
      instant for in situ optical investigations of blast-induced dynamic fracture. To
      illustrate the capability of this system, an explosion experiment using a 2D
      epoxy plate is conducted, yielding consistent results between two methods. This
      novel system provides rich experimental data including local-field information
      for the crack tip and full-field information for blasting waves.

PMID- 29195388
TI  - Saturation of the photoneutralization of a H- beam in continuous operation.
AB  - An unprecedented, greater than 50%, photodetachment rate is obtained on a H- beam
      in the continuous regime. The key element of the experimental setup is a medium
      finesse optical cavity, suspended around the anion beam, which makes it possible
      to recycle the photon flux in the interaction region, at the crossing between the
      anion and laser beams. The cavity is injected by a narrow-linewidth ytterbium
      doped fibre laser, at the wavelength 1064 nm. The light power stored in the
      cavity is about 14 kW for 24 W of input light power. Similar greater-than-50%
      photo-neutralization efficiencies can be contemplated for beams with kinetic
      energies much larger than 1.2 keV of the presently used H- beam, given the fact
      that the stored light power can be increased, for larger beam diameters, by
      several orders of magnitude. The technique can thus be relied on to design novel
      D0 injectors, for fusion reactors, with a much better efficiency than the
      molecular-collision based injectors presently developed for ITER. It can also be
      applied to the production of neutral beams of any species that can be
      conveniently prepared in the form of an anion beam, provided that efficient light
      power storage can be achieved for the corresponding photodetachment wavelength.

PMID- 29195389
TI  - Multiplexed fluctuation-dissipation-theorem calibration of optical tweezers
      inside living cells.
AB  - In order to apply optical tweezers-based force measurements within an
      uncharacterized viscoelastic medium such as the cytoplasm of a living cell, a
      quantitative calibration method that may be applied in this complex environment
      is needed. We describe an improved version of the fluctuation-dissipation-theorem
      calibration method, which has been developed to perform in situ calibration in
      viscoelastic media without prior knowledge of the trapped object. Using this
      calibration procedure, it is possible to extract values of the medium's
      viscoelastic moduli as well as the force constant describing the optical trap. To
      demonstrate our method, we calibrate an optical trap in water, in polyethylene
      oxide solutions of different concentrations, and inside living fission yeast (S.
      pombe).

PMID- 29195390
TI  - An embeddable optical strain gauge based on a buckled beam.
AB  - We report, for the first time, a low cost, compact, and novel mechanically
      designed extrinsic Fabry-Perot interferometer (EFPI)-based optical fiber sensor
      with a strain amplification mechanism for strain measurement. The fundamental
      design principle includes a buckled beam with a coated gold layer, mounted on two
      grips. A Fabry-Perot cavity is produced between the buckled beam and the endface
      of a single mode fiber (SMF). A ceramic ferrule is applied for supporting and
      orienting the SMF. The principal sensor elements are packaged and protected by
      two designed metal shells. The midpoint of the buckled beam will experience a
      deflection vertically when the beam is subjected to a horizontally/axially
      compressive displacement. It has been found that the vertical deflection of the
      beam at midpoint can be 6-17 times larger than the horizontal/axial displacement,
      which forms the basis of a strain amplification mechanism. The user-configurable
      buckling beam geometry-based strain amplification mechanism enables the strain
      sensor to achieve a wide range of strain measurement sensitivities. The designed
      EFPI was used to monitor shrinkage of a square brick of mortar. The strain was
      measured during the drying/curing stage. We envision that it could be a good
      strain sensor to be embedded in civil materials/structures under a harsh
      environment for a prolonged period of time.

PMID- 29195391
TI  - Micro-view-cell for phase behaviour and in situ Raman analysis of heterogeneously
      catalysed CO2 hydrogenation.
AB  - The operando study of CO2 hydrogenation is fundamental for a more rational
      optimisation of heterogeneous catalyst and reactor designs. To further complement
      the established efficiency of microreactors in reaction screening and bridge the
      operating and optical gaps, a micro-view-cell is presented for Raman microscopy
      at extreme conditions with minimum flow interference for genuine reaction
      analysis. Based on a flat sapphire window unit sealed in a plug flow-type
      enclosure holding the sample, the cell features unique 14 mm working distance and
      0.36 numerical aperture and resists 400  degrees C and 500 bars. The use of the
      cell as an in situ tool for fast process monitoring and surface catalyst
      characterisation is demonstrated with phase behaviour and chemical analysis of
      the methanol synthesis over a commercial Cu/ZnO/Al2O3 catalyst.

PMID- 29195392
TI  - A millimeter magnetic trap for a dual (85Rb and 87Rb) species atom
      interferometer.
AB  - We present a magnetic trap for cold atoms near a surface of a millimeter-sized
      atom chip. The trap allows us to capture a large number of atoms with modest
      electrical currents (40 A) and to generate large magnetic gradients (>300 G cm
      1). Here we report a mixture containing 6 * 109 atoms for the two rubidium
      isotopes 87Rb and 85Rb. This device does not require cleanroom facilities nor
      micro-machining technologies which makes its construction easier. In addition our
      design allows the implementation of an optical dipole trap with a laser beam
      passing through the chip.

PMID- 29195393
TI  - 1 MUs broadband frequency sweeping reflectometry for plasma density and
      fluctuation profile measurements.
AB  - Frequency swept reflectometry has reached the symbolic value of 1 MUs sweeping
      time; this performance has been made possible, thanks to an improved control of
      the ramp voltage driving the frequency source. In parallel, the memory depth of
      the acquisition system has been upgraded and can provide up to 200 000 signals
      during a plasma discharge. Additional improvements regarding the trigger delay
      determination of the acquisition and the voltage ramp linearity required by this
      ultra-fast technique have been set. While this diagnostic is traditionally
      dedicated to the plasma electron density profile measurement, such a fast
      sweeping rate can provide the study of fast plasma events and turbulence with
      unprecedented time and radial resolution from the edge to the core. Experimental
      results obtained on ASDEX Upgrade plasmas are presented to demonstrate the
      performances of the diagnostic.

PMID- 29195394
TI  - Note: A NDIR instrument for multicomponent gas detection using the galvanometer
      modulation.
AB  - The non-dispersive infrared (NDIR) instruments are widely applied to
      multicomponent gas detection in many fields. In this paper, a NDIR instrument
      using the galvanometer modulation is proposed, which has a common optical path
      for multicomponent gas detection. Compared with the conventional NDIR instrument
      using the chopper modulation, the proposed instrument with a simpler
      configuration has better detection efficiency and stability. The proposed
      instrument has been successfully used to measure the main gas components of
      vehicle emissions. The NDIR instrument using the galvanometer modulation has
      great potential for remote sensing application, where multicomponent gas is
      always spatially inhomogeneous.

PMID- 29195395
TI  - Simultaneous excitation of 85Rb and 87Rb isotopes inside a microfabricated vapor
      cell with double-RF fields for a chip-scale MZ magnetometer.
AB  - We report a novel method adopting two RF fields to simultaneously excite 85Rb and
      87Rb isotopes for an MZ type atomic magnetometer. The MZ magnetometer adopts a 6
      mm3 microfabricated vapor cell with natural abundance rubidium and 0.74 amagat
      nitrogen as buffer gas inside. The excessively broadened magnetic resonance
      signals of the two rubidium isotopes overlap with each other and cause
      deterioration in accuracy and sensitivity performance. To solve this problem, a
      Double-RF Field Method (DRFM) is proposed, which adopts two RF fields with a
      central frequency ratio of 2:3. Compared with traditional Single-RF Field Method
      (SRFM), the DRFM reduces the detection error by over 50% and improves the
      sensitivity by more than 10%. The experiments are conducted at three temperatures
      and under various static magnetic fields. Theoretical models are also built to
      discuss the performance improvement of the magnetometer by the DRFM against the
      SRFM. This method provides a way to improve the performance of chip-scale MZ
      atomic magnetometers with low cost natural abundance rubidium.

PMID- 29195397
TI  - Howland current source for high impedance load applications.
AB  - For Electrical Impedance Spectroscopy (EIS) applications, the Enhanced Howland
      Current Source (EHCS) is a popular choice as an excitation circuit due to its
      simplicity, reliability, and safety. However, its output impedance degradation at
      high frequency leads to errors that are unacceptable for high load impedance
      applications, such as the ones which use dry or microelectrodes. Based on a
      proposed mathematical model, this work designed an EHCS circuit which includes an
      output current buffer and frequency compensation. PSpice simulations were
      performed as proof of concept, and then the measured data were collected for
      comparison. For the proposed circuit, called here Load-in-the-Loop Compensated
      Enhanced Howland Source (LLC-EHCS), the results showed that the output current
      errors are lower than 1% up to 3.7 MHz over the load range of 560-2200 Omega and
      1.2 MHz with 5.6 kOmega. On the other hand, for the case of the standard EHCS
      circuit, these frequencies are 170 and 80 kHz, respectively. Also, the output
      linear swing was found to be 3 times higher than the EHCS. It can be concluded
      that the proposed LLC-EHCS may be widely used as an excitation circuit for high
      load and wide bandwidth EIS applications.

PMID- 29195396
TI  - Note: A highly symmetrical piezoelectric motor with self-matching friction and
      large output force.
AB  - We present a new stacked TunaDrive motor with two intact piezoelectric stacks
      being spring-clamped by a pair of parallel highly polished zirconia ceramic rods.
      Compared with the earlier version we presented with five stacks, it has a simpler
      and more compact structure and is much easier to build. Although the usage of
      piezoelectric material is cut by ~35%, the motor can still provide a large output
      force of ~1.92 N, which is nearly the same as that of the earlier version. The
      simple and symmetrical structure, high rigidity, and large output force make the
      new motor an ideal tool for coarse approach with nanometer precision.

PMID- 29195398
TI  - Automatic emissive probe apparatus for efficient plasma potential measurements.
AB  - The improved inflection point method of emissive probe is the most accurate
      method for plasma potential measurements, but its manual operation is quite
      cumbersome and time-consuming. This paper describes the design and test of an
      automatic emissive probe apparatus for efficient plasma potential measurements.
      The apparatus consists of a computer controlled data acquisition (DAQ) card, a
      working circuit composed of a biasing unit and a heating unit, as well as the
      emissive probe. The main feature of the apparatus is that both the biasing scan
      and the heating scan of the probe are controlled by the computer program through
      analog outputs of the DAQ card, which easily realizes the required timing between
      the biasing and heating scans of the probe. The apparatus can automatically
      execute the improved inflection point method of emissive probe and give the
      plasma potential result. The advantages of high-accuracy, high-efficiency, and
      durability of probe filament make the apparatus promising for extensive use in
      plasma potential measurements.

PMID- 29195399
TI  - A pinhole camera for ultrahigh-intensity laser plasma experiments.
AB  - A pinhole camera is an important instrument for the detection of radiation in
      laser plasmas. It can monitor the laser focus directly and assist in the analysis
      of the experimental data. However, conventional pinhole cameras are difficult to
      use when the target is irradiated by an ultrahigh-power laser because of the high
      background of hard X-ray emission generated in the laser/target region.
      Therefore, an improved pinhole camera has been developed that uses a grazing
      incidence mirror that enables soft X-ray imaging while avoiding the effect of
      hard X-ray from hot dense plasmas.

PMID- 29195400
TI  - A novel AFM-based 5-axis nanoscale machine tool for fabrication of nanostructures
      on a micro ball.
AB  - This paper presents a novel atomic force microscopy (AFM)-based 5-axis nanoscale
      machine tool developed to fabricate nanostructures on different annuli of the
      micro ball. Different nanostructures can be obtained by combining the scratching
      trajectory of the AFM tip with the movement of the high precision air-bearing
      spindle. The center of the micro ball is aligned to be coincided with the
      gyration center of the high precision to guarantee the machining process during
      the rotating of the air-bearing spindle. Processing on different annuli of the
      micro ball is achieved by controlling the distance between the center of the
      micro ball and the rotation center of the AFM head. Nanostructures including
      square cavities, circular cavities, triangular cavities, and an annular
      nanochannel are machined successfully on the three different circumferences of a
      micro ball with a diameter of 1500 MUm. Moreover, the influences of the error
      motions of the high precision air-bearing spindle and the eccentric between the
      micro ball and the gyration center of the high precision air-bearing spindle on
      the processing position error on the micro ball are also investigated. This
      proposed machining method has the potential to prepare the inertial confinement
      fusion target with the expected dimension defects, which would advance the
      application of the AFM tip-based nanomachining approach.

PMID- 29195401
TI  - High speed displacement measurement based on electro-magnetic induction applied
      to electromagnetically driven ring expansion.
AB  - Investigating the mechanism of electromagnetic forming (EMF) becomes a hot topic
      in the field of metal forming. The high speed up to 200 m/s in EMF makes it a
      real challenge to capture the forming process. To this end, a new method for
      measuring displacement at high speed based on electromagnetic induction has been
      developed. Specifically this is used to measure the displacement of an expanding
      metal ring driven by a pulsed magnetic field; this is one of the basic EMF
      processes. The new method is simple and practical, and it combines high-speed
      response with adequate precision. The new measurement system consists of a
      printed circuit board (PCB) and a Rogowski probe. Eleven coaxial annular
      detecting probes are arranged in the PCB plate to acquire induced voltage at
      different positions, and a Rogowski probe is used to measure the current in the
      driving coil. The displacement of the ring is deduced by analyzing the output
      voltages of the detecting probes and the Rogowski probe. The feasibility of the
      method is verified by comparing the results with pictures from a high speed
      camera taken simultaneously.

PMID- 29195402
TI  - Flame exposure time on Langmuir probe degradation, ion density, and thermionic
      emission for flame temperature.
AB  - The paper examines the effect of exposure time of Langmuir probes in an
      atmospheric premixed methane-air flame. The effects of probe size and material
      composition on current measurements were investigated, with molybdenum and
      tungsten probe tips ranging in diameter from 0.0508 to 0.1651 mm. Repeated
      prolonged exposures to the flame, with five runs of 60 s, resulted in gradual
      probe degradations (-6% to -62% area loss) which affected the measurements. Due
      to long flame exposures, two ion saturation currents were observed, resulting in
      significantly different ion densities ranging from 1.16 * 1016 to 2.71 * 1019 m
      3. The difference between the saturation currents is caused by thermionic
      emissions from the probe tip. As thermionic emission is temperature dependent,
      the flame temperature could thus be estimated from the change in current. The
      flame temperatures calculated from the difference in saturation currents (1734
      1887 K) were compared to those from a conventional thermocouple (1580-1908 K).
      Temperature measurements obtained from tungsten probes placed in rich flames
      yielded the highest percent error (9.66%-18.70%) due to smaller emission current
      densities at lower temperatures. The molybdenum probe yielded an accurate
      temperature value with only 1.29% error. Molybdenum also demonstrated very low
      probe degradation in comparison to the tungsten probe tips (area reductions of 6%
      vs. 58%, respectively). The results also show that very little exposure time (<5
      s) is needed to obtain a valid ion density measurement and that prolonged flame
      exposures can yield the flame temperature but also risks damage to the Langmuir
      probe tip.

PMID- 29195403
TI  - A dynamic point-load test for quantifying rock dynamic strength parameters.
AB  - The point-load test (PLT) has been widely used in the field and in the laboratory
      to estimate the strength of rock materials. The PLT is easy and quick to perform
      and it is suitable for samples with irregular shapes and therefore has found wide
      applications. The measured point-load strength (PLS) is considered as a strength
      index and it has been correlated to the rock compressive strength. To address the
      engineering applications where the loading is dynamic, the PLT is extended to its
      dynamic version in this study. The dynamic loading is exerted to the rock
      specimen using a split Hopkinson pressure bar system. Two conical steel platens
      are attached to the incident bar and transmitted bar, respectively, to apply the
      point load to the disc specimen. To enable quasi-static analysis, the pulse
      shaper technique is utilized to achieve the dynamic force balance. The
      flexibility of the dynamic PLT method is demonstrated by the application to a
      well-studied granitic rock-Laurentian granite. The correlation between the
      dynamic PLS and the dynamic strength of the same rock is established.

PMID- 29195404
TI  - Noise spectra in balanced optical detectors based on transimpedance amplifiers.
AB  - We present a thorough theoretical analysis and experimental study of the shot and
      electronic noise spectra of a balanced optical detector based on an operational
      amplifier connected in a transimpedance scheme. We identify and quantify the
      primary parameters responsible for the limitations of the circuit, in particular,
      the bandwidth and shot-to-electronic noise clearance. We find that the shot noise
      spectrum can be made consistent with the second-order Butterworth filter, while
      the electronic noise grows linearly with the second power of the frequency. Good
      agreement between the theory and experiment is observed; however, the
      capacitances of the operational amplifier input and the photodiodes appear
      significantly higher than those specified in manufacturers' datasheets. This
      observation is confirmed by independent tests.

PMID- 29195405
TI  - A polarization converting device for an interfering enhanced CPT atomic clock.
AB  - With interfering enhanced coherent population trapping (CPT) signals, a CPT
      atomic clock with improved frequency stability performance can be realized. We
      explore an optical device that converts single-polarized bichromatic light to
      left and right circularly polarized superposed bichromatic light to generate
      interfering enhanced CPT resonance with atoms. We have experimentally studied a
      tabletop CPT atomic clock apparatus with a microfabricated 87Rb atomic chip-scale
      cell, and the study results show that it is promising to realize a compact CPT
      atomic clock, even a chip-scale CPT atomic clock through microfabrication, with
      improved frequency stability performance.

PMID- 29195406
TI  - Semiconductor sharpeners providing a subnanosecond voltage rise time of GW-range
      pulses.
AB  - The article describes semiconductor sharpeners providing a subnanosecond voltage
      rise time of GW-range pulses. The sharpeners are made as stacks of series
      connected dynistor structures built into an oil-filled coaxial line with 48 Omega
      wave impedance at the place of an inner conductor. Two sequential sections of
      pulse sharpening are used. An input voltage pulse has the amplitude of 540 kV
      with the rise time of ~1.2 ns at 0.2-0.9 level from the amplitude and voltage
      rise rate of ~0.3 MV/ns. After pulse propagation through the sharpening sections,
      its rise time is reduced down to 360 ps, and the voltage rise rate is increased
      up to ~0.95 MV/ns. Peak power of the sharpened pulse is within the range of 4.5
      5.5 GW. The sharpeners are tested at a pulse repetition frequency of up to 1 kHz.
      Sharpener operation is studied by numerical simulation methods. Experimental
      waveforms of output pulses and the corresponding calculated voltage-time
      dependences are in statistical agreement.

PMID- 29195407
TI  - A large ion beam device for laboratory solar wind studies.
AB  - The Colorado Solar Wind Experiment is a new device constructed at the Institute
      for Modeling Plasma, Atmospheres, and Cosmic Dust at the University of Colorado.
      A large cross-sectional Kaufman ion source is used to create steady state plasma
      flow to model the solar wind in an experimental vacuum chamber. The plasma beam
      has a diameter of 12 cm at the source, ion energies of up to 1 keV, and ion flows
      of up to 0.1 mA/cm2. Chamber pressure can be reduced to 4 * 10-5 Torr under
      operating conditions to suppress ion-neutral collisions and create a
      monoenergetic ion beam. The beam profile has been characterized by a Langmuir
      probe and an ion energy analyzer mounted on a two-dimensional translation stage.
      The beam profile meets the requirements for planned experiments that will study
      solar wind interaction with lunar magnetic anomalies, the charging and dynamics
      of dust in the solar wind, plasma wakes and refilling, and the wakes of
      topographic features such as craters or boulders. This article describes the
      technical details of the device, initial operation and beam characterization, and
      the planned experiments.

PMID- 29195408
TI  - A microfluidic sub-critical water extraction instrument.
AB  - This article discusses a microfluidic subcritical water extraction (SCWE) chip
      for autonomous extraction of amino acids from astrobiologically interesting
      samples. The microfluidic instrument is composed of three major components. These
      include a mixing chamber where the soil sample is mixed and agitated with the
      solvent (water), a subcritical water extraction chamber where the sample is
      sealed with a freeze valve at the chip inlet after a vapor bubble is injected
      into the inlet channels to ensure the pressure in the chip is in equilibrium with
      the vapor pressure and the slurry is then heated to <=200  degrees C in the SCWE
      chamber, and a filter or settling chamber where the slurry is pumped to after
      extraction. The extraction yield of the microfluidic SCWE chip process ranged
      from 50% compared to acid hydrolysis and 80%-100% compared to a benchtop
      microwave SCWE for low biomass samples.

PMID- 29195409
TI  - Triggering breakdown voltage of a high-current, two-electrode graphite gas switch
      assisted by ultraviolet pre-ionization.
AB  - A simple ultraviolet pre-ionization device designed to extend the lifetime of a
      high current, two-electrode graphite gas switch is described in this paper. The
      effects of UV-illumination on decreasing the triggering breakdown voltage were
      studied in theory and experiments. The results showed that UV-illumination can
      provide extra initial electrons on the cathode surface and make more air
      molecules in the excited state, which resulted in positive effects in reducing
      the triggering breakdown voltage and jitter. However, the effects became weak as
      the pressure increased; the reason of this phenomenon was that the ultraviolet
      absorption rate of the air molecules increased with the rising pressure, leading
      to a reduction of the ultraviolet intensity on the discharge gap. The largest
      value of the triggering breakdown voltage decreased was 13.5 kV under 100 kPa,
      and the reliable operation gap distance can extend another 1.2 mm, which was
      equivalent to 500 shots in our experiments.

PMID- 29195410
TI  - Invited Review Article: Measurements of the Newtonian constant of gravitation, G.
AB  - By many accounts, the Newtonian constant of gravitation G is the fundamental
      constant that is most difficult to measure accurately. Over the past three
      decades, more than a dozen precision measurements of this constant have been
      performed. However, the scatter of the data points is much larger than the
      uncertainties assigned to each individual measurement, yielding a Birge ratio of
      about five. Today, G is known with a relative standard uncertainty of 4.7 * 10-5,
      which is several orders of magnitudes greater than the relative uncertainties of
      other fundamental constants. In this article, various methods to measure G are
      discussed. A large array of different instruments ranging from the simple torsion
      balance to the sophisticated atom interferometer can be used to determine G. Some
      instruments, such as the torsion balance can be used in several different ways.
      In this article, the advantages and disadvantages of different instruments as
      well as different methods are discussed. A narrative arc from the historical
      beginnings of the different methods to their modern implementation is given.
      Finally, the article ends with a brief overview of the current state of the art
      and an outlook.

PMID- 29195411
TI  - Hand-held synchronous scan spectrometer for in situ and immediate detection of
      live/dead bacteria ratio.
AB  - The design, construction, and operation of a hand-held synchronously scanned,
      excitation-emission, double monochromator spectrometer is described. Data show
      that it is possible to record and display within minutes the fluorescence spectra
      and ratio of live/dead bacteria in situ. Excitation emission matrix contour plots
      display clearly bacteria fluorescence spectra before and after UV inactivation,
      respectively. The separation of the fluorescence band maxima of molecular
      components, such as tryptophan, tyrosine, and DNA, may be distinguished in the
      diffused fluorescence spectra of bacteria and mixtures.

PMID- 29195412
TI  - Radiation resistance of elastomeric O-rings in mixed neutron and gamma fields:
      Testing methodology and experimental results.
AB  - Materials and components employed in the presence of intense neutron and gamma
      fields are expected to absorb high dose levels that may induce deep modifications
      of their physical and mechanical properties, possibly causing loss of their
      function. A protocol for irradiating elastomeric materials in reactor mixed
      neutron and gamma fields and for testing the evolution of their main mechanical
      and physical properties with absorbed dose has been developed. Four elastomeric
      compounds used for vacuum O-rings, one fluoroelastomer polymer (FPM) based and
      three ethylene propylene diene monomer rubber (EPDM) based, presently available
      on the market have been selected for the test. One EPDM is rated as radiation
      resistant in gamma fields, while the other elastomers are general purpose
      products. Particular care has been devoted to dosimetry calculations, since
      absorbed dose in neutron fields, unlike pure gamma fields, is strongly dependent
      on the material composition and, in particular, on the hydrogen content. The
      products have been tested up to about 2 MGy absorbed dose. The FPM based
      elastomer, in spite of its lower dose absorption in fast neutron fields, features
      the largest variations of properties, with a dramatic increase in stiffness and
      brittleness. Out of the three EPDM based compounds, one shows large and rapid
      changes in the main mechanical properties, whereas the other two feature more
      stable behaviors. The performance of the EPDM rated as radiation resistant in
      pure gamma fields does not appear significantly better than that of the standard
      product. The predictive capability of the accelerated irradiation tests performed
      as well as the applicable concepts of threshold of radiation damage is discussed
      in view of the use of the examined products in the selective production of exotic
      species facility, now under construction at the Legnaro National Laboratories of
      the Italian Istituto Nazionale di Fisica Nucleare. It results that a careful
      account of dose rate effects and oxygen penetration in the material, both during
      test irradiations and in operating conditions, is needed to obtain reliable
      predictions.

PMID- 29195413
TI  - Control system of neoclassical tearing modes in real time on HL-2A tokamak.
AB  - The stability and performance of tokamak plasmas are routinely limited by various
      magneto-hydrodynamic instabilities, such as neoclassical tearing modes (NTMs).
      This paper presents a rather simple method to control the NTMs in real time (RT)
      on a tokamak, including the control principle of a feedback approach for RT
      suppression and stabilization for the NTMs. The control system combines Mirnov,
      electron cyclotron emission, and soft X-ray diagnostics used for determining the
      NTM positions. A methodology for fast detection of 2/1 or 3/2 NTM positions with
      129 * 129 grid reconstruction is elucidated. The forty poloidal angles for
      steering the electron cyclotron resonance heating (ECRH)/electron cyclotron
      current drive launcher are used to establish the alignment of antenna mirrors
      with the center of the NTM and to ensure launcher emission intersecting with the
      rational surface of a magnetic island. Pilot experiments demonstrate the RT
      control capability to trace the conventional tearing modes (CTMs) in the HL-2A
      tokamak. The 2/1 CTMs have been suppressed or stabilized by the ECRH power
      deposition on site or with the steerable launcher.

PMID- 29195414
TI  - A high precision flat crystal spectrometer compatible for ultra-high vacuum light
      source.
AB  - We report on a flat crystal spectrometer (FCS) featuring a differently pumped
      rotary feedthrough and double detectors connected to a crystal chamber by
      extendable bellows built at the Shanghai EBIT Laboratory. It was designed to
      overcome defects such as oil contamination, little distance from the detector to
      the crystal and others of an early FCS equipped at the same laboratory, but still
      keeps a large detectable angle range of detectors and brings new features and
      functions such as the Bond method measurement and double-crystal measurement
      which are based on the two-detector and large bellow design. This new FCS could
      cover an energy range of measurable photons from 570 eV to 10 keV and reach a
      vacuum better than 6 * 10-10 Torr and thus is compatible for coupling directly to
      ultra-high vacuum light sources. Off-line tests of the FCS were undertaken where
      Kalpha x-rays from solid titanium were measured and analyzed. Measurements of
      transitions in He-like argon ions were performed when the spectrometer was
      directly connected to Shanghai EBIT, and the width of the x-ray source was
      monitored simultaneously using an x-ray slit imaging system. An observed spectral
      line broadening was 0.869 eV corresponding to a resolving power of 3600,
      including Doppler broadening of the x-ray source. Taking account of the measured
      source width, we made simulations using the SHADOW 3 code and got a nominal
      resolving power of 6500 for the spectrometer. This high nominal resolving power
      is due to a longer distance from the crystal to the detector, comparing with that
      in the early FCS.

PMID- 29195415
TI  - A micro-CL system and its applications.
AB  - The computed laminography (CL) method is preferable to computed tomography for
      the non-destructive testing of plate-like objects. A micro-CL system is developed
      for three-dimensional imaging of plate-like objects. The details of the micro-CL
      system are described, including the system architecture, scanning modes, and
      reconstruction algorithm. The experiment results of plate-like fossils, insulated
      gate bipolar translator module, ball grid array packaging, and printed circuit
      board are also presented to demonstrate micro-CL's ability for 3D imaging of flat
      specimens and universal applicability in various fields.

PMID- 29195416
TI  - Non-native phonetic learning is destabilized by exposure to phonological
      variability before and after training.
AB  - Phonological variability is a key factor in many phonetic training studies, but
      it is unclear whether variability is universally helpful for learners. The
      current study explored variability and sleep consolidation in non-native phonetic
      learning. Two groups of participants were trained on a non-native contrast in one
      vowel context (/u/) and differed in whether they were also tested on an untrained
      context (/i/). Participants exposed to two vowels during the test were less
      accurate in perception of trained speech sounds and showed no overnight
      improvement. These findings suggest that introducing variability even in test
      phases may destabilize learning and prevent consolidation-based performance
      improvements.

PMID- 29195417
TI  - Quantification of stiffness measurement errors in resonant ultrasound
      spectroscopy of human cortical bone.
AB  - Resonant ultrasound spectroscopy (RUS) is the state-of-the-art method used to
      investigate the elastic properties of anisotropic solids. Recently, RUS was
      applied to measure human cortical bone, an anisotropic material with low Q-factor
      (20), which is challenging due to the difficulty in retrieving resonant
      frequencies. Determining the precision of the estimated stiffness constants is
      not straightforward because RUS is an indirect method involving minimizing the
      distance between measured and calculated resonant frequencies using a model. This
      work was motivated by the need to quantify the errors on stiffness constants due
      to different error sources in RUS, including uncertainties on the resonant
      frequencies and specimen dimensions and imperfect rectangular parallelepiped (RP)
      specimen geometry. The errors were first investigated using Monte Carlo
      simulations with typical uncertainty values of experimentally measured resonant
      frequencies and dimensions assuming a perfect RP geometry. Second, the exact
      specimen geometry of a set of bone specimens were recorded by synchrotron
      radiation micro-computed tomography. Then, a "virtual" RUS experiment is proposed
      to quantify the errors induced by imperfect geometry. Results show that for a
      bone specimen of ~1 degrees  perpendicularity and parallelism errors, an accuracy
      of a few percent ( <6.2%) for all the stiffness constants and engineering moduli
      is achievable.

PMID- 29195418
TI  - Poro-acoustoelastic constants based on Pade approximation.
AB  - Stress-induced velocity variations for porous rocks are generally characterized
      by a strong nonlinear dependence on stress associated with complex deformations
      under loading. The classical theory of poro-acoustoelasticity with high-order
      elastic constants is based on the Taylor expansion of the strain energy function,
      encountering problems of divergence and limitless elastic wave velocities in
      describing stress-associated velocity variations, especially for high effective
      stresses. The extension of the theory beyond the high-order elastic constants
      based on the Pade approximation to the strain energy function is addressed in
      this article. The resultant acoustoelastic constants are characteristics of a
      reasonable theoretical limit in elastic wave velocities with increasing effective
      stresses, avoiding some of the problems associated with high-order elastic
      constants such as decreasing moduli with increasing effective pressure at high
      effective pressure, possibly implying the microstructural dependence of elastic
      constants. That is, the loading stress increases strain energy and wave velocity,
      but also induces frame-related attenuation, which in turn reduces stiffness and
      elastic constants. The Pade nonlinear constants can be reduced for low effective
      stresses to the conventional acoustoelastic constants based on the Taylor
      expansion. Theoretical results are compared with ultrasonic measurements for a
      perfectly elastic crystal, topaz (Al2SiO4F2), and a porous rock, demonstrating
      that the Pade-approximation-based acoustoelasticity gives a more accurate
      description of stress-associated velocity variations, especially for higher
      effective stresses.

PMID- 29195419
TI  - Finite difference time domain modelling of a point-excited elastic plate
      radiating into an acoustic cavity.
AB  - Finite difference time domain (FDTD) models are developed to solve the
      vibroacoustic problem of a thin elastic plate undergoing point force excitation
      and radiating into an acoustic cavity. Vibroacoustic modelling using FDTD can be
      computationally expensive because structure-borne sound wavespeeds are relatively
      high and a fine spatial resolution is often required. In this paper a scaling
      approach is proposed and validated to overcome this problem through modifications
      to the geometry and physical properties. This allows much larger time steps to be
      used in the model which significantly reduces the computation time. Additional
      reductions in computation time are achieved by introducing an alternative
      approach to model the boundaries between the air and the solid media.
      Experimental validation is carried out using a thin metal plate inside a small
      reverberant room. The agreement between FDTD and measurements confirms the
      validity of both approaches as well as the FDTD implementation of a thin plate as
      a three-dimensional solid that can support multiple wave types. Below the lowest
      room mode, there are large spatial variations in the sound field within the
      cavity due to the radiating plate; this indicates the importance of having a
      validated FDTD model for low-frequency vibroacoustic problems.

PMID- 29195420
TI  - Toward clinical application of landmark-based speech analysis: Landmark
      expression in normal adult speech.
AB  - The goal of clinical speech analysis is to describe abnormalities in speech
      production that affect a speaker's intelligibility. Landmark analysis identifies
      abrupt changes in a speech signal and classifies them according to their acoustic
      profiles. These acoustic markers, called landmarks, may help describe
      intelligibility deficits in disordered speech. As a first step toward clinical
      application of landmark analysis, the present study describes expression of
      landmarks in normal speech. Results of the study revealed that syllabic, glottal,
      and burst landmarks consist of 94% of all landmarks, and suggest the effect of
      gender needs to be considered for the analysis.

PMID- 29195421
TI  - Noise interference with echo delay discrimination in bat biosonar.
AB  - Echolocating big brown bats (Eptesicus fuscus) were trained in a two-choice task
      to discriminate differences in the delay of electronic echoes at 1.7 ms delay (30
      cm simulated range). Difference thresholds (~45 MUs) were comparable to
      previously published results. At selected above-threshold differences (116 and
      232 MUs delay), performance was measured in the presence of wideband random noise
      at increasing amplitudes in 10-dB steps to determine the noise level that
      prevented discrimination. Performance eventually failed, but the bats increased
      the amplitude and duration of their broadcasts to compensate for increasing
      noise, which allowed performance to persist at noise levels about 25 dB higher
      than without compensation. In the 232-MUs delay discrimination condition, echo
      signal-to-noise ratio (2E/N0) was 8-10 dB at the noise level that depressed
      performance to chance. Predicted echo-delay accuracy using big brown bat signals
      follows the Cramer-Rao bound for signal-to-noise ratios above 15 dB, but worsens
      below 15 dB due to side-peak ambiguity. At 2E/N0 = 7-10 dB, predicted Cramer-Rao
      delay accuracy would be about 1 MUs; considering side-peak ambiguity it would be
      about 200-300 MUs. The bats' 232 MUs performance reflects the intrusion of side
      peak ambiguity into delay accuracy at low signal-to-noise ratios.

PMID- 29195422
TI  - A transfer learning approach to goodness of pronunciation based automatic
      mispronunciation detection.
AB  - Goodness of pronunciation (GOP) is the most widely used method for automatic
      mispronunciation detection. In this paper, a transfer learning approach to GOP
      based mispronunciation detection when applying maximum F1-score criterion (MFC)
      training to deep neural network (DNN)-hidden Markov model based acoustic models
      is proposed. Rather than train the whole network using MFC, a DNN is used, whose
      hidden layers are borrowed from native speech recognition with only the softmax
      layer trained according to the MFC objective function. As a result, significant
      mispronunciation detection improvement is obtained. In light of this, the two
      stage transfer learning based GOP is investigated in depth. The first stage
      exploits the hidden layer(s) to extract phonetic-discriminating features. The
      second stage uses a trainable softmax layer to learn the human standard for
      judgment. The validation is carried out by experimenting with different
      mispronunciation detection architectures using acoustic models trained by
      different criteria. It is found that it is preferable to use frame-level cross
      entropy to train the hidden layer parameters. Classifier based mispronunciation
      detection is further experimented with using features computed by transfer
      learning based GOP and it is shown that it also helps to achieve better results.

PMID- 29195423
TI  - Evaluation of an experimental electrohydraulic discharge device for
      extracorporeal shock wave lithotripsy: Pressure field of sparker array.
AB  - In this paper, an extracorporeal shock wave source composed of small ellipsoidal
      sparker units is described. The sparker units were arranged in an array designed
      to produce a coherent shock wave of sufficient strength to fracture kidney
      stones. The objective of this paper was to measure the acoustical output of this
      array of 18 individual sparker units and compare this array to commercial
      lithotripters. Representative waveforms acquired with a fiber-optic probe
      hydrophone at the geometric focus of the sparker array indicated that the sparker
      array produces a shock wave (P+ ~40-47 MPa, P- ~2.5-5.0 MPa) similar to shock
      waves produced by a Dornier HM-3 or Dornier Compact S. The sparker array's
      pressure field map also appeared similar to the measurements from a HM-3 and
      Compact S. Compared to the HM-3, the electrohydraulic technology of the sparker
      array produced a more consistent SW pulse (shot-to-shot positive pressure value
      standard deviation of +/-4.7 MPa vs +/-3.3 MPa).

PMID- 29195424
TI  - Absorption, scattering, and radiation force efficiencies in the longitudinal wave
      scattering by a small viscoelastic particle in an isotropic solid.
AB  - Analytical expressions of the absorption, scattering, and elastic radiation force
      efficiency factors are derived for the longitudinal plane wave scattering by a
      small viscoelastic particle in a lossless solid matrix. The particle is assumed
      to be much smaller than the incident wavelength, i.e., the so-called long
      wavelength (Rayleigh) approximation. The efficiencies are dimensionless
      quantities that represent the absorbed and scattering powers and the elastic
      radiation force on the particle. In the quadrupole approximation, they are
      expressed in terms of contrast functions (bulk and shear moduli, and density)
      between the particle and solid matrix. The results for a high-density
      polyethylene particle embedded in an aluminum matrix agree with those obtained
      with the partial wave expansion method. Additionally, the connection between the
      elastic radiation force and forward scattering function is established through
      the optical theorem. The present results should be useful for ultrasound
      characterization of particulate composites, and the development of implanted
      devices activated by radiation force.

PMID- 29195426
TI  - Acoustic realization of Mandarin neutral tone and tone sandhi in infant-directed
      speech and Lombard speech.
AB  - Mandarin lexical tones are modified in both infant-directed speech (IDS) and
      Lombard speech, resulting in tone hyperarticulation. However, it is unclear if
      these registers also alter contextual tones (neutral tone and tone sandhi) and if
      such phonetic modification might affect acquisition of these tones. This study
      therefore examined how neutral tone and tone sandhi are realized in IDS, and how
      their acoustic manifestations compare with those in Lombard speech, where the
      communicative needs of listeners differ. Neutral tone and tone sandhi productions
      were elicited from 15 Mandarin-speaking mothers during (1) interactions with
      their 12-month-old infants (IDS), (2) in conversation with a Mandarin-speaking
      adult in a noisy environment (Lombard speech), and (3) in conversation with a
      Mandarin-speaking adult in a quiet environment (adult-directed speech). The
      results showed that, although both contextual tones were modified in IDS and
      Lombard speech, their key tone features were maintained. In addition, IDS and
      Lombard speech modified these tones differently: IDS increased pitch height and
      modified pitch contour, while Lombard speech increased pitch height only. The
      realization of neutral tone and tone sandhi across registers is discussed with
      reference to listeners' different communicative needs.

PMID- 29195427
TI  - Pitch matching in bimodal cochlear implant patients: Effects of frequency,
      spectral envelope, and level.
AB  - This study systematically investigated the effects of frequency, level, and
      spectral envelope on pitch matching in twelve bimodal cochlear implant (CI)
      users. The participants were asked to vary the frequency and level of a pure or
      complex tone (adjustable sounds) presented in the non-implanted ear to match the
      pitch and loudness of different reference stimuli presented to the implanted ear.
      Three reference sounds were used: single electrode pulse trains, pure tones, and
      piano notes. The data showed a significant effect of the frequency and complexity
      of the reference sounds. No significant effect of the level of the reference
      sounds was found. The magnitude of effect of frequency was compressed in the
      implanted ear: on average a difference of seven semitones in the non-implanted
      ear induced the same pitch change as a difference of 19 to 24 semitones for a
      stimulus presented to the implanted ear. The spectral envelope of the adjustable
      sound presented to the non-implanted ear also had a significant effect. The
      matched frequencies were higher by an average of six semitones for the pure tone
      compared to a complex tone. Overall, the CI listeners might have matched the
      stimuli based on timbre characteristics such as brightness.

PMID- 29195428
TI  - Temporal effects in interaural and sequential level difference perception.
AB  - Temporal effects in interaural level difference (ILD) perception are not well
      understood. While it is often assumed that ILD sensitivity is independent of the
      temporal stimulus properties, a reduction of ILD sensitivity for stimuli with a
      high modulation rate has been reported (known under the term binaural
      adaptation). Experiment 1 compared ILD thresholds and sequential-level-difference
      (SLD) thresholds using 300-ms bandpass-filtered pulse trains (centered at 4 kHz)
      with rates of 100, 400, and 800 pulses per second (pps). In contrast to the SLD
      thresholds, ILD thresholds were elevated at 800 pps, consistent with literature
      data that had previously been attributed to binaural adaptation. Experiment 2
      showed better ILD sensitivity for pulse trains than for pure tones, suggesting
      that amplitude modulation enhances ILD sensitivity. The present ILD data and
      binaural adaptation data from the literature were predicted by a model combining
      well-established auditory periphery front-ends with an interaural comparison
      stage. The model also accounted for other published ILD data, including target
      ILD thresholds in diotic forward and backward fringes and ILD thresholds with
      different amounts of interaural correlation. Overall, a variety of temporal
      effects in ILD perception, including binaural adaptation, appear to be largely
      attributable to monaural peripheral auditory processing.

PMID- 29195429
TI  - Stochastic sediment property inversion in Shallow Water 06.
AB  - Received time-series at a short distance from the source allow the identification
      of distinct paths; four of these are direct, surface and bottom reflections, and
      sediment reflection. In this work, a Gibbs sampling method is used for the
      estimation of the arrival times of these paths and the corresponding probability
      density functions. The arrival times for the first three paths are then employed
      along with linearization for the estimation of source range and depth, water
      column depth, and sound speed in the water. Propagating densities of arrival
      times through the linearized inverse problem, densities are also obtained for the
      above parameters, providing maximum a posteriori estimates. These estimates are
      employed to calculate densities and point estimates of sediment sound speed and
      thickness using a non-linear, grid-based model. Density computation is an
      important aspect of this work, because those densities express the uncertainty in
      the inversion for sediment properties.

PMID- 29195430
TI  - Comparing the effect of aperture extension on the peak sidelobe level of sparse
      arrays.
AB  - The reduced number of sensors in sparse arrays create high peak sidelobe levels
      (PSLs). This letter compares the PSLs of minimum redundancy arrays (MRAs),
      minimum hole arrays (MHAs), and co-prime sensor arrays (CSAs) (conventionally
      beamformed and product processed) with fully populated uniform linear arrays
      (ULAs) as a function of aperture using both numerical simulations and
      experimental data. This letter finds that PSLs of MRAs, MHAs, and conventionally
      processed CSAs are much higher than the ULA PSL and are largely insensitive to
      aperture extension. In contrast, CSA product processing decreases the PSL with
      increasing aperture, eventually matching the ULA PSL.

PMID- 29195431
TI  - Two laboratory methods of assessing annoyance due to railway noise and vibration.
AB  - In laboratory experiments, total annoyance due to combined noise and vibration
      and partial annoyances due to each source in the presence of the other can be
      assessed in two ways: during separate sessions dedicated to the evaluation of
      each kind of annoyance, and during the same session. This letter examines the
      difference between annoyance responses provided by the two methods. No
      differences were found between partial (respectively, total) annoyance responses
      measured during separate sessions and those measured during the same session. The
      latter procedure allows reducing the number of stimuli to which the participants
      are subjected.

PMID- 29195432
TI  - Dynamic temporal behaviour of the keyboard action on the Hammond organ and its
      perceptual significance.
AB  - The Hammond organ is one of earliest electronic instruments and is still used
      widely in contemporary popular music. One of its main sonic features is the "key
      click," a transient that occurs upon note onset, caused by the mechanical
      bouncing of the nine electric contacts actuated during each key press. A study of
      the dynamic mechanical behaviour of the contact bounces is presented, showing
      that the velocity, the type of touch and, more in general, the temporal evolution
      of the key position, all affect different characteristics of the contact bounces.
      A second study focuses on the listener's perception of the generated sound and
      finds that listeners can classify sounds produced on the Hammond organ according
      to the type of touch and velocity used. It is concluded that the Hammond organ is
      a touch-responsive instrument and that the gesture used to produce a note affects
      the generated sound across multiple dimensions. The control available at the
      fingertips of the musician is therefore such that it cannot be easily reduced to
      a single scalar velocity parameter, as is common practice in modern digital
      emulations of the instrument.

PMID- 29195433
TI  - Reliability of individual differences in degraded speech perception.
AB  - Listeners' speech perception abilities vary extensively in challenging listening
      conditions. There is little evidence as to whether this variability is a result
      of true, stable individual differences or just variability arising from
      measurement error. This study examines listeners' word recognition abilities
      across multiple sessions and a variety of degraded speech tasks (noise-vocoded,
      time-compressed, and speech in babble noise). Participants transcribed isolated
      single syllable words presented in all three degradation types and repeated these
      tasks (with different words) on a separate day. Correlations of transcription
      accuracy demonstrate that individual differences in performance are reliable
      across sessions. In addition, performance on all three degradation types was
      correlated. These results suggest that differences in performance on degraded
      speech perception tasks for normal hearing listeners are robust and that there
      are underlying factors that promote the ability to understand degraded speech
      regardless of the specific manner of degradation. Uncovering these general
      performance factors may provide insight into the salient performance variance
      observed in listeners with hearing impairment.

PMID- 29195434
TI  - Last call: Passive acoustic monitoring shows continued rapid decline of
      critically endangered vaquita.
AB  - The vaquita is a critically endangered species of porpoise. It produces
      echolocation clicks, making it a good candidate for passive acoustic monitoring.
      A systematic grid of sensors has been deployed for 3 months annually since 2011;
      results from 2016 are reported here. Statistical models (to compensate for non
      uniform data loss) show an overall decline in the acoustic detection rate between
      2015 and 2016 of 49% (95% credible interval 82% decline to 8% increase), and
      total decline between 2011 and 2016 of over 90%. Assuming the acoustic detection
      rate is proportional to population size, approximately 30 vaquita (95% credible
      interval 8-96) remained in November 2016.

PMID- 29195435
TI  - Consistent modelling of wind turbine noise propagation from source to receiver.
AB  - The unsteady nature of wind turbine noise is a major reason for annoyance. The
      variation of far-field sound pressure levels is not only caused by the continuous
      change in wind turbine noise source levels but also by the unsteady flow field
      and the ground characteristics between the turbine and receiver. To take these
      phenomena into account, a consistent numerical technique that models the sound
      propagation from the source to receiver is developed. Large eddy simulation with
      an actuator line technique is employed for the flow modelling and the
      corresponding flow fields are used to simulate sound generation and propagation.
      The local blade relative velocity, angle of attack, and turbulence
      characteristics are input to the sound generation model. Time-dependent blade
      locations and the velocity between the noise source and receiver are considered
      within a quasi-3D propagation model. Long-range noise propagation of a 5 MW wind
      turbine is investigated. Sound pressure level time series evaluated at the source
      time are studied for varying wind speeds, surface roughness, and ground
      impedances within a 2000 m radius from the turbine.

PMID- 29195436
TI  - Band structure analysis of phononic crystals based on the Chebyshev interval
      method.
AB  - Due to environmental changes and manufacturing errors, uncertainties inherently
      exist in phononic crystals, especially in the material properties and geometric
      parameters. To handle the uncertainties with limited information, two different
      methods are proposed for band structure analysis of phononic crystals with
      uncertainties. One is the Monte Carlo method (MCM). The main shortcoming of it is
      the high computational cost. The other is the simplex Chebyshev polynomial
      expansion (SPCE) method. In addition, the computational efficiency of the SPCE
      method is much higher. In the SPCE method, the simplex Chebyshev is employed to
      estimate the band structures of phononic crystals. Meanwhile, the simplified
      incremental sampling strategy is introduced for the simplex Chebyshev to retain
      calculation accuracy and improve computational efficiency simultaneously. In the
      Chebyshev surrogate model, the samples yielded with the MCM are used to calculate
      the interval ranges of the band structures in phononic crystals. Three numerical
      examples, including a two-dimensional (2D) Helmholtz resonator phononic crystal,
      a 2D solid-solid phononic crystal, and a three-dimensional phononic crystal, are
      introduced to verify the effectiveness and efficiency of the proposed method.

PMID- 29195437
TI  - A revised metric for calculating acoustic dispersion applied to stop inventories.
AB  - Dispersion Theory [DT; Liljencrants and Lindblom (1972). Language 12(1), 839-862]
      claims that acoustically dispersed vowel inventories should be typologically
      common. Dispersion is often quantified using triangle area between three mean
      vowel formant points. This approach is problematic; it ignores distributions,
      which affect speech perception [Clayards, Tanenhaus, Aslin, and Jacobs (2008).
      Cognition 108, 804-809]. This letter proposes a revised metric for calculating
      dispersion which incorporates covariance. As a test case, modeled vocal tract
      articulatory-acoustic data of stop consonants [Schwartz, Boe, Badin, and Sawallis
      (2012). J. Phonetics 40, 20-36] are examined. Although the revised metric does
      not recover DT predictions for stop inventories, it changes results, showing that
      dispersion results depend on metric choice, which is often overlooked. The metric
      can be used in any acoustic space to include information about within-category
      variation when calculating dispersion.

PMID- 29195438
TI  - L2 voice recognition: The role of speaker-, listener-, and stimulus-related
      factors.
AB  - Previous studies examined various factors influencing voice recognition and
      learning with mixed results. The present study investigates the separate and
      combined contribution of these various speaker-, stimulus-, and listener-related
      factors to voice recognition. Dutch listeners, with arguably incomplete
      phonological and lexical knowledge in the target language, English, learned to
      recognize the voice of four native English speakers, speaking in English, during
      four-day training. Training was successful and listeners' accuracy was shown to
      be influenced by the acoustic characteristics of speakers and the sound
      composition of the words used in the training, but not by lexical frequency of
      the words, nor the lexical knowledge of the listeners or their phonological
      aptitude. Although not conclusive, listeners with a lower working memory capacity
      seemed to be slower in learning voices than listeners with a higher working
      memory capacity. The results reveal that speaker-related, listener-related, and
      stimulus-related factors accumulate in voice recognition, while lexical
      information turns out not to play a role in successful voice learning and
      recognition. This implies that voice recognition operates at the prelexical
      processing level.

PMID- 29195439
TI  - The spatial coherence of noise fields evoked by continuous source distributions.
AB  - In this work, analytic expressions for the spatial coherence of noise fields are
      derived in the modal domain with the aim of providing a sparse representation.
      For this purpose, the sound field in a region of interest is expressed in terms
      of a given pressure distribution on a virtual surrounding cylindrical or
      spherical surface. According to the Huygens-Fresnel principle, the sound pressure
      on this surface is represented by a continuous distribution of elementary line or
      point sources, where orthogonal basis functions characterize the spatial
      properties. To describe spatially windowed pressure distributions with arbitrary
      angular extensions, orthogonal basis functions of limited angular support are
      proposed. As special cases, circular and spherical pressure distributions with
      uncorrelated source modes of equal power are investigated. It is shown that these
      distributions result, respectively, in cylindrically isotropic and spherically
      isotropic, i.e., diffuse noise fields. The analytic expressions derived in this
      work allow for a prediction of the spatial coherence between arbitrary positions
      within the region of interest, such that no microphones need to be placed at the
      actual points of interest. Simulation results are presented to validate the
      derived relations.

PMID- 29195440
TI  - Ambient noise forecasting with a large acoustic array in a complex shallow water
      environment.
AB  - Forecasting ambient noise levels in the ocean can be a useful way of
      characterizing the detection performance of sonar systems and projecting bounds
      on performance into the near future. The assertion is that noise forecasting can
      be improved with a priori knowledge of source positions coupled with the ability
      to resolve closely separated sources in bearing. One example of such a system is
      the large aperture research array located at the South Florida Test Facility.
      Given radar and Automatic Identification System defined source positions and
      environmental information, transmission loss (TL) is computed from known source
      positions to the array. Source levels (SLs) of individual ships are then
      estimated from computed TL and the pre-determined beam response of the array
      using a non-negative least squares algorithm. Ambient noise forecasts are formed
      by projecting the estimated SLs along known ship tracks. Ambient noise forecast
      estimates are compared to measured beam level data and mean-squared error is
      computed. A mean squared error as low as 3.5 dB is demonstrated in 30 min
      forecast estimates when compared to ground truth.

PMID- 29195441
TI  - A time-domain model for seafloor scattering.
AB  - Bottom scattering is important for a number of underwater applications: it is a
      source of noise in target detection and a source of information for sediment
      classification and geoacoustic inversion. While current models can predict the
      effective interface scattering strength for layered sediments, these models
      cannot directly compute the ensemble averaged mean-square pressure. A model for
      bottom scattering due to a point source is introduced which provides a full-wave
      solution for mean-square scattered pressure as a function of time under first
      order perturbation theory. Examples of backscatter time series from various types
      of seafloors will be shown, and the advantages and limitations of this model will
      be discussed.

PMID- 29195442
TI  - Sound production patterns of big-clawed snapping shrimp (Alpheus spp.) are
      influenced by time-of-day and social context.
AB  - Snapping shrimp are perhaps the most pervasive sources of biological sound in the
      ocean. The snapping sounds of cryptic shrimp colonies in shallow coastal habitats
      worldwide create a near-continuous crackling with high spatiotemporal
      variability, yet the underlying acoustic ecology is not well understood. This
      study investigated sound production rates and acoustic behavior of snapping
      shrimp species common in the Western Atlantic Ocean and Gulf of Mexico (Alpheus
      heterochaelis and Alpheus angulosus). Snap rates were measured in a controlled
      laboratory setting under natural light, temperature, and substrate conditions for
      shrimp held individually, in pairs, and in a ten-shrimp mesocosm, to test
      hypotheses that acoustic activity varies with time-of-day and social context.
      Spontaneous snapping was observed for 81 out of 84 solitary shrimp monitored.
      Time-of-day influenced snap output for individuals and same-sex pairs-higher
      rates occurred during dusk and night, compared to daylight hours, but this
      pattern was inconsistent for opposite-sex pairs and a mixed-sex group. These
      laboratory results provide insight into behavioral rhythms that may influence
      snapping patterns in natural populations, and underscore the limited
      understanding of a major sound source in marine environments.

PMID- 29195443
TI  - Sequential dependencies in pitch judgments.
AB  - Studies that measure pitch discrimination relate a subject's response on each
      trial to the stimuli presented on that trial, but there is evidence that behavior
      depends also on earlier stimulation. Here, listeners heard a sequence of tones
      and reported after each tone whether it was higher or lower in pitch than the
      previous tone. Frequencies were determined by an adaptive staircase targeting 75%
      correct, with interleaved tracks to ensure independence between consecutive
      frequency changes. Responses for this specific task were predicted by a model
      that took into account the frequency interval on the current trial, as well as
      the interval and response on the previous trial. This model was superior to
      simpler models. The dependence on the previous interval was positive
      (assimilative) for all subjects, consistent with persistence of the sensory
      trace. The dependence on the previous response was either positive or negative,
      depending on the subject, consistent with a subject-specific suboptimal response
      strategy. It is argued that a full stimulus + response model is necessary to
      account for effects of stimulus history and obtain an accurate estimate of
      sensory noise.

PMID- 29195444
TI  - Detection of keyboard vibrations and effects on perceived piano quality.
AB  - Two experiments were conducted on an upright and a grand piano, both either
      producing string vibrations or conversely being silent after the initial
      keypress, while pianists were listening to the feedback from a synthesizer
      through insulating headphones. In a quality experiment, participants unaware of
      the silent mode were asked to play freely and then rate the instrument according
      to a set of attributes and general preference. Participants preferred the
      vibrating over the silent setup, and preference ratings were associated to
      auditory attributes of richness and naturalness in the low and middle ranges.
      Another experiment on the same setup measured the detection of vibrations at the
      keyboard, while pianists played notes and chords of varying dynamics and
      duration. Sensitivity to string vibrations was highest in the lowest register and
      gradually decreased up to note D5. After the percussive transient, the tactile
      stimuli exhibited spectral peaks of acceleration whose perceptibility was
      demonstrated by tests conducted in active touch conditions. The two experiments
      confirm that piano performers perceive vibratory cues of strings mediated by
      spectral and spatial summations occurring in the Pacinian system in their
      fingertips, and suggest that such cues play a role in the evaluation of quality
      of the musical instrument.

PMID- 29195445
TI  - Cochlear implant simulator with independent representation of the full spiral
      ganglion.
AB  - In cochlear implant simulation with vocoders, narrow-band carriers deliver the
      envelopes from each analysis band to the cochlear positions of the simulated
      electrodes. However, this approach does not faithfully represent the continuous
      nature of the spiral ganglion. The proposed "SPIRAL" vocoder simulates current
      spread by mixing all envelopes across many tonal carriers. SPIRAL demonstrated
      that the classic finding of reduced speech-intelligibility benefit with
      additional electrodes could be due to current spread. SPIRAL produced lower
      speech reception thresholds than an equivalent noise vocoder. These thresholds
      are stable for between 20 and 160 carriers.

PMID- 29195447
TI  - Using reciprocity to derive the far field displacements due to buried sources and
      scatterers.
AB  - It is shown that elastodynamic reciprocity provides a simpler approach for
      deriving the far-field displacements due to buried (sub-surface) sources in a
      half-space, compared with integral transform techniques. The auxiliary fields
      employed in this approach are the fields associated with the reflection of plane
      waves of the three possible polarisations, and the required far field can be
      expressed in terms of these well-known auxiliary fields. The crucial step in this
      approach is to evaluate a surface integral involving cross-work terms between an
      outgoing spherical wavefront and the auxiliary fields consisting of incident and
      reflected plane waves. This integral can be evaluated by the stationary phase
      approximation for the two-dimensional case, or by a generalisation of this
      approximation for the three-dimensional case. Although this evaluation involves
      several distinct contributions, the final result is shown to be very simple, and
      it can be interpreted as a generalisation of a known result for the one
      dimensional case, whereby the net contribution arises only from counter
      propagating waves of the same mode. The results derived for a buried force are
      extended to the case of buried cracks by exploiting the body force equivalents
      for displacement discontinuities across a surface.

PMID- 29195448
TI  - The influence of visual distance on the room-acoustic experience of
      auralizations.
AB  - Auralizations have become more prevalent in architectural acoustics and virtual
      reality. Studies have shown that by employing a methodical calibration procedure,
      ecologically/perceptually valid auralizations can be obtained. Another study
      demonstrated a manner to include dynamic voice directivity with results
      indicating these auralizations were judged significantly more plausible than
      auralizations with static source orientations. With the increased plausibility of
      auralizations, it is possible to study room-acoustic experience employing virtual
      reality, having confidence that the results also apply to real-life situations.
      Limited studies have examined the influence of visuals on room-acoustic
      experience. Using a virtual reality framework, this study investigated the
      influence of visuals on the room-acoustic experience of auralizations.
      Evaluations compared dynamic voice auralizations coherently matched with
      visualization positions to incoherently matched audio-visual pairs. Based on the
      results, the test population could be divided into three subgroups: (1) those who
      judged auralizations more acoustically distant with increased visual distance,
      (2) those who judged auralizations louder with increased visual distance, and (3)
      those whose audio judgment was uninfluenced by the visual stimulus.

PMID- 29195446
TI  - A common microstructure in behavioral hearing thresholds and stimulus-frequency
      otoacoustic emissions.
AB  - Behavioral hearing thresholds and otoacoustic emission (OAE) spectra often
      exhibit quasiperiodic fluctuations with frequency. For behavioral and OAE
      responses to single tones-the latter referred to as stimulus-frequency
      otoacoustic emissions (SFOAEs)-this microstructure has been attributed to
      intracochlear reflections of SFOAE energy between its region of generation and
      the middle ear boundary. However, the relationship between behavioral and SFOAE
      microstructures, as well as their presumed dependence on the properties of the
      SFOAE-generation mechanism, have yet to be adequately examined. To address this,
      behavioral thresholds and SFOAEs evoked by near-threshold tones were compared in
      12 normal-hearing female subjects. The microstructures observed in thresholds and
      both SFOAE amplitudes and delays were found to be strikingly similar. SFOAE phase
      accumulated an integer number of cycles between the frequencies of microstructure
      maxima, consistent with a dependence of microstructure periodicity on SFOAE
      propagation delays. Additionally, microstructure depth was correlated with SFOAE
      magnitude in a manner resembling that predicted by the intracochlear reflection
      framework, after assuming reasonable values of parameters related to middle ear
      transmission. Further exploration of this framework may yield more precise
      estimates of such parameters and provide insight into their frequency dependence.

PMID- 29195449
TI  - Ship localization in Santa Barbara Channel using machine learning classifiers.
AB  - Machine learning classifiers are shown to outperform conventional matched field
      processing for a deep water (600 m depth) ocean acoustic-based ship range
      estimation problem in the Santa Barbara Channel Experiment when limited
      environmental information is known. Recordings of three different ships of
      opportunity on a vertical array were used as training and test data for the feed
      forward neural network and support vector machine classifiers, demonstrating the
      feasibility of machine learning methods to locate unseen sources. The classifiers
      perform well up to 10 km range whereas the conventional matched field processing
      fails at about 4 km range without accurate environmental information.

PMID- 29195450
TI  - Generation of 1/f noise from a broken-symmetry model for the arbitrary absolute
      pitch of musical melodies.
AB  - A model is presented to generate power spectrum noise with intensity proportional
      to 1/f  as a function of frequency f. The model arises from a broken-symmetry
      variable, which corresponds to absolute pitch, where fluctuations occur in an
      attempt to restore that symmetry, influenced by interactions in the creation of
      musical melodies.

PMID- 29195451
TI  - Why orchestral musicians are bound to wear earplugs: About the ineffectiveness of
      physical measures to reduce sound exposure.
AB  - Symphony orchestra musicians are exposed to noise levels that put them at risk of
      developing hearing damage. This study evaluates the potential effectivity of
      common control measures used in orchestras on open stages with a typical
      symphonic setup. A validated acoustic prediction model is used that calculates
      binaural sound exposure levels at the ears of all musicians in the orchestra. The
      model calculates the equivalent sound levels for a performance of the first 2 min
      of the 4th movement of Mahler's 1st symphony, which can be considered
      representative for loud orchestral music. Calculated results indicate that
      risers, available space, and screens at typical positions do not significantly
      influence sound exposure. A hypothetical scenario with surround screens shows
      that, even when shielding all direct sound from others, sound exposure is reduced
      moderately with the largest effect on players in loud sections. In contrast, a
      dramatic change in room acoustic conditions only leads to considerable reductions
      for soft players. It can be concluded that significant reductions are only
      reached with extreme measures that are unrealistic. It seems impossible for the
      studied physical measures to be effective enough to replace hearing protection
      devices such as ear plugs.

PMID- 29195452
TI  - Evaluation and calibration of mobile phones for noise monitoring application.
AB  - The increasing number and quality of sensors integrated in mobile phones have
      paved the way for sensing schemes driven by city dwellers. The sensing quality
      can drastically depend on the mobile phone, and appropriate calibration
      strategies are needed. This paper evaluates the quality of noise measurements
      acquired by a variety of Android phones. The Ambiciti application was developed
      so as to acquire a larger control over the acquisition process. Pink and
      narrowband noises were used to evaluate the phones' accuracy at levels ranging
      from background noise to 90 dB(A) inside the lab. Conclusions of this evaluation
      lead to the proposition of a calibration strategy that has been embedded in
      Ambiciti and applied to more than 50 devices during public events. A performance
      analysis addressed the range, accuracy, precision, and reproducibility of
      measurements. After identification and removal of a bias, the measurement error
      standard deviation is below 1.2 dB(A) within a wide range of noise levels [45 to
      75 dB(A)], for 12 out of 15 phones calibrated in the lab. In the perspective of
      citizens-driven noise sensing, in situ experiments were carried out, while
      additional tests helped to produce recommendations regarding the sensing context
      (grip, orientation, moving speed, mitigation, frictions, wind).

PMID- 29195453
TI  - A hybrid phononic crystal for roof application.
AB  - Phononic crystal is a type of acoustic material, and the study of phononic
      crystals has attracted great attention from national research institutions.
      Meanwhile, noise reduction in the low-frequency range has always encountered
      difficulties and troubles in the engineering field. In order to obtain a unique
      and effective low-frequency noise reduction method, in this paper a low frequency
      noise attenuation system based on phononic crystal structure is proposed and
      demonstrated. The finite element simulation of the band gap is consistent with
      the final test results. The effects of structure parameters on the band gaps were
      studied by changing the structure parameters and the band gaps can be controlled
      by suitably tuning structure parameters. The structure and results provide a good
      support for phononic crystal structures engineering application.

PMID- 29195454
TI  - Broadband ship noise and its potential impacts on Indo-Pacific humpback dolphins:
      Implications for conservation and management.
AB  - Ship noise pollution has raised considerable concerns among regulatory agencies
      and cetacean researchers worldwide. There is an urgent need to quantify ship
      noise in coastal areas and assess its potential biological impacts. In this
      study, underwater broadband noise from commercial ships in a critical habitat of
      Indo-Pacific humpback dolphins was recorded and analyzed. Data analysis indicated
      that the ship noise caused by the investigated commercial ships with an average
      length of 134 +/- 81 m, traveling at 18.8 +/- 2.5 km/h [mean +/- standard
      deviation (SD), n = 21] comprises mid-to-high components with frequencies
      approaching and exceeding 100 kHz, and the ship noise could be sensed auditorily
      by Indo-Pacific humpback dolphins within most of their sensitive frequency range.
      The contributions of ship noise to ambient noise were highest in two third-octave
      bands with center frequencies of 8 and 50 kHz, which are within the sensitive
      hearing range of Indo-Pacific humpback dolphins and overlap the frequency of
      sounds that are biologically significant to the dolphins. It is estimated that
      ship noise in these third-octave bands can be auditorily sensed by and
      potentially affect the dolphins within 2290 +/- 1172 m and 848 +/- 358 m (mean +/
      SD, n = 21), respectively.

PMID- 29195455
TI  - Ontogeny of individual and litter identity signaling in grunts of piglets.
AB  - Many studies have shown that animal vocalizations can signal individual identity
      and group/family membership. However, much less is known about the ontogeny of
      identity information-when and how this individual/group distinctiveness in
      vocalizations arises and how it changes during the animal's life. Recent findings
      suggest that even species that were thought to have limited vocal plasticity
      could adjust their calls to sound more similar to each other within a group. It
      has already been shown that sows can acoustically distinguish their own offspring
      from alien piglets and that litters differ in their calls. Surprisingly,
      individual identity in piglet calls has not been reported yet. In this paper,
      this gap is filled, and it is shown that there is information about piglet
      identity. Information about litter identity is confirmed as well. Individual
      identity increased with age, but litter vocal identity did not increase with age.
      The results were robust as a similar pattern was apparent in two situations
      differing in arousal: isolation and back-test. This paper argues that, in
      piglets, increased individual discrimination results from the rapid growth of
      piglets, which is likely to be associated with growth and diversification of the
      vocal tract rather than from social effects and vocal plasticity.

PMID- 29195456
TI  - Monitoring ice thickness and elastic properties from the measurement of leaky
      guided waves: A laboratory experiment.
AB  - The decline of Arctic sea ice extent is one of the most spectacular signatures of
      global warming, and studies converge to show that this decline has been
      accelerating over the last four decades, with a rate that is not reproduced by
      climate models. To improve these models, relying on comprehensive and accurate
      field data is essential. While sea ice extent and concentration are accurately
      monitored from microwave imagery, an accurate measure of its thickness is still
      lacking. Moreover, measuring observables related to the mechanical behavior of
      the ice (such as Young's modulus, Poisson's ratio, etc.) could provide better
      insights in the understanding of sea ice decline, by completing current knowledge
      so far acquired mostly from radar and sonar data. This paper aims at
      demonstrating on the laboratory scale that these can all be estimated
      simultaneously by measuring seismic waves guided in the ice layer. The experiment
      consisted of leaving a water tank in a cold room in order to grow an ice layer at
      its surface. While its thickness was increasing, ultrasonic guided waves were
      generated with a piezoelectric source, and measurements were subsequently
      inverted to infer the thickness and mechanical properties of the ice with very
      good accuracy.

PMID- 29195457
TI  - Cylindrical heat conduction and structural acoustic models for enclosed fiber
      array thermophones.
AB  - Calculation of the heat loss for thermophone heating elements is a function of
      their geometry and the thermodynamics of their surroundings. Steady-state
      behavior is difficult to establish or evaluate as heat is only flowing in one
      direction in the device. However, for a heating element made from an array of
      carbon fibers in a planar enclosure, several assumptions can be made, leading to
      simple solutions of the heat equation. These solutions can be used to more
      carefully determine the efficiency of thermophones of this geometry. Acoustic
      response is predicted with the application of a Helmholtz resonator and thin
      plate structural acoustics models. A laboratory thermophone utilizing a sparse
      horizontal array of fine (6.7 MUm diameter) carbon fibers is designed and tested.
      Experimental results are compared with the model. The model is also used to
      examine the optimal array density for maximal efficiency.

PMID- 29195458
TI  - Predicting effects of hearing-instrument signal processing on consonant
      perception.
AB  - This study investigated the influence of hearing-aid (HA) and cochlear-implant
      (CI) processing on consonant perception in normal-hearing (NH) listeners.
      Measured data were compared to predictions obtained with a speech perception
      model [Zaar and Dau (2017). J. Acoust. Soc. Am. 141, 1051-1064] that combines an
      auditory processing front end with a correlation-based template-matching back
      end. In terms of HA processing, effects of strong nonlinear frequency compression
      and impulse-noise suppression were measured in 10 NH listeners using consonant
      vowel stimuli. Regarding CI processing, the consonant perception data from DiNino
      et al. [(2016). J. Acoust. Soc. Am. 140, 4404-4418] were considered, which were
      obtained with noise-vocoded vowel-consonant-vowel stimuli in 12 NH listeners. The
      inputs to the model were the same stimuli as were used in the corresponding
      experiments. The model predictions obtained for the two data sets showed a large
      agreement with the perceptual data both in terms of consonant recognition and
      confusions, demonstrating the model's sensitivity to supra-threshold effects of
      hearing-instrument signal processing on consonant perception. The results could
      be useful for the evaluation of hearing-instrument processing strategies,
      particularly when combined with simulations of individual hearing impairment.

PMID- 29195459
TI  - Subcortical amplitude modulation encoding deficits suggest evidence of cochlear
      synaptopathy in normal-hearing 18-19 year olds with higher lifetime noise
      exposure.
AB  - Noise exposure and aging can damage cochlear synapses required for suprathreshold
      listening, even when cochlear structures needed for hearing at threshold remain
      unaffected. To control for effects of aging, behavioral amplitude modulation (AM)
      detection and subcortical envelope following responses (EFRs) to AM tones in 25
      age-restricted (18-19 years) participants with normal thresholds, but different
      self-reported noise exposure histories were studied. Participants with more noise
      exposure had smaller EFRs and tended to have poorer AM detection than less
      exposed individuals. Simulations of the EFR using a well-established cochlear
      model were consistent with more synaptopathy in participants reporting greater
      noise exposure.

PMID- 29195460
TI  - Multilevel modeling and regression of community annoyance to transportation
      noise.
AB  - A multilevel (hierarchical) model is devised that separates noise tolerance into
      variations occurring at the levels of individual listeners and communities. This
      approach successfully describes the characteristics of real community
      transportation noise surveys, with the individual- and community-level variations
      producing distinct statistical signatures, both of which are evident in the
      surveys. Predictions are provided for quantities such as the probability of
      annoyance based on the observed noise level and statistical parameters
      characterizing the community tolerance. Regression analyses are performed using a
      multilevel, generalized linear model, which provides an appropriate
      generalization encompassing both no pooling (separate community-by-community
      analysis) and full pooling (all communities together) of survey data, and enables
      noise tolerances and their variations at the individual and community levels to
      be distinguished and quantified. Variations in individual tolerance and sound
      exposure within communities are found to be larger than variations in tolerance
      between communities; however, the variations between communities are still
      significant and observable. Analysis of multiple types of transportation noise
      with the multilevel model indicates that tolerance is highest for railway noise
      with low vibrations, followed by roadway noise, airport noise, and railway noise
      with high vibrations, as consistent with previous studies.

PMID- 29195461
TI  - Using the trapped energy ratio for source depth discrimination with a horizontal
      line array: Theory and experimental results.
AB  - The problem of acoustic source depth discrimination was introduced as a way to
      get basic information on source depth in configurations where accurate depth
      estimation is not feasible. It is a binary classification problem, aiming to
      evaluate whether the source is near the surface or submerged. Herein, the
      classification relies on a signal measured with a horizontal line array in
      shallow water. Knowing the source-array distance is not required but the source
      bearing has to be close to the array endfire. Signal processing relies on a
      normal-mode propagation model, and thus requires prior knowledge of the mode
      characteristics. The decision relies on an estimation of the trapped energy ratio
      in mode space. The performance is predicted with simulations and Monte Carlo
      methods, allowing one to compare several estimators based on different mode
      filters, and to choose an appropriate decision threshold. The impact on
      performance of frequency, noise level, horizontal aperture, and environmental
      mismatch is numerically studied. Finally, the approach is validated on
      experimental data acquired with a horizontal line array deployed off the coast of
      New Jersey, and the impact of errors in the environmental model is illustrated.
      The investigated approach successfully identifies a surface ship and a submerged
      towed source.

PMID- 29195462
TI  - Cross-beam coherence of infrasonic signals at local and regional ranges.
AB  - Signals collected by infrasound arrays require continuous analysis by skilled
      personnel or by automatic algorithms in order to extract useable information.
      Typical pieces of information gained by analysis of infrasonic signals collected
      by multiple sensor arrays are arrival time, line of bearing, amplitude, and
      duration. These can all be used, often with significant accuracy, to locate
      sources. A very important part of this chain is associating collected signals
      across multiple arrays. Here, a pairwise, cross-beam coherence method of signal
      association is described that allows rapid signal association for high signal-to
      noise ratio events captured by multiple infrasound arrays at ranges exceeding 150
      km. Methods, test cases, and results are described.

PMID- 29195463
TI  - ACOUSTICAL STANDARDS NEWS.
AB  - American National Standards (ANSI Standards) developed by Accredited Standards
      Committees S1, S2, S3, S3/SC 1, and S12 in the areas of acoustics, mechanical
      vibration and shock, bioacoustics, animal bioacoustics, and noise, respectively,
      are published by the Acoustical Society of America (ASA). In addition to these
      standards, ASA publishes a catalog of Acoustical American National Standards. To
      receive a copy of the latest Standards catalog, please contact Neil
      Stremmel.Comments are welcomed on all material in Acoustical Standards News.This
      Acoustical Standards News section in JASA and other information on the Standards
      Program of the Acoustical Society of America are available via the ASA home page:
      http://acousticalsociety.org.

PMID- 29195464
TI  - Wind noise spectra in small Reynolds number turbulent flows.
AB  - Wind noise spectra caused by wind from fans in indoor environments have been
      found to be different from those measured in outdoor atmospheric conditions.
      Although many models have been developed to predict outdoor wind noise spectra
      under the assumption of large Reynolds number [Zhao, Cheng, Qiu, Burnett, and Liu
      (2016). J. Acoust. Soc. Am. 140, 4178-4182, and the references therein], they
      cannot be applied directly to the indoor situations because the Reynolds number
      of wind from fans in indoor environments is usually much smaller than that
      experienced in atmospheric turbulence. This paper proposes a pressure structure
      function model that combines the energy-containing and dissipation ranges so that
      the pressure spectrum for small Reynolds number turbulent flows can be
      calculated. The proposed pressure structure function model is validated with the
      experimental results in the literature, and then the obtained pressure spectrum
      is verified with the numerical simulation and experiment results. It is
      demonstrated that the pressure spectrum obtained from the proposed pressure
      structure function model can be utilized to estimate wind noise spectra caused by
      turbulent flows with small Reynolds numbers.

PMID- 29195465
TI  - Extracting the time domain Green's function from ocean ambient noise using
      acoustic vector sensors.
AB  - A function that closely resembles the two-point time-domain Green's function
      (TDGF) representing the time delays associated with multipath between the two
      sensors can be recovered by correlating the noise field measured by two sensors.
      Here, a technique for extracting the TDGF from ambient ocean noise using acoustic
      vector sensors is presented. Experimental results suggest that the averaging time
      to extract TDGF is greatly reduced if sound pressure sensors (hydrophones) are
      replaced by acoustic vector sensors. The direct arrival and bottom bounce arrival
      were extracted successfully with only 1 min of vertical velocity data, while the
      bottom bounce arrival was not extracted with even 10 min of sound pressure data.

PMID- 29195466
TI  - Doppler spectra of airborne ultrasound forward scattered by the rough surface of
      open channel turbulent water flows.
AB  - Experimental data are presented on the Doppler spectra of airborne ultrasound
      forward scattered by the rough dynamic surface of an open channel turbulent flow.
      The data are numerically interpreted based on a Kirchhoff approximation for a
      stationary random water surface roughness. The results show a clear link between
      the Doppler spectra and the characteristic spatial and temporal scales of the
      water surface. The decay of the Doppler spectra is proportional to the velocity
      of the flow near the surface. At higher Doppler frequencies the measurements show
      a less steep decrease of the Doppler spectra with the frequency compared to the
      numerical simulations. A semi-empirical equation for the spectrum of the surface
      elevation in open channel turbulent flows over a rough bed is provided. The
      results of this study suggest that the dynamic surface of open channel turbulent
      flows can be characterized remotely based on the Doppler spectra of forward
      scattered airborne ultrasound. The method does not require any equipment to be
      submerged in the flow and works remotely with a very high signal to noise ratio.

PMID- 29195467
TI  - Characterization of gain and directivity of exponential horn receivers.
AB  - It is difficult and expensive to match the sensitivity of the most sensitive
      vertebrate ears with off-the-shelf microphones due to the self-noise of the
      sensor. The extremely small apertures of microelectromechanical microphones
      create options to use horn waveguides to amplify sound prior to transduction
      without resulting in an unacceptably narrow directivity. Substantial gain can be
      achieved at wavelengths larger than the horn. An analytical model of an
      exponential horn embedded in a rigid spherical housing was formulated to describe
      the gain relative to a free-field receiver as a function of frequency and angle
      of arrival. For waves incident on-axis, the analytical model provided an accurate
      estimate of gain at high frequencies as validated by experimental measurement.
      Numerical models, using the equivalent source method, can account for higher
      order modes and comprehensively describe the acoustic scattering within and
      around the horn for waves arriving from any direction. Results show the
      directivity of horn receivers were adequately described by the analytical model
      up to a critical wavelength, and the mechanisms of deviation in gain at high
      frequencies and large angles of arrival were identified.

PMID- 29195468
TI  - Incorporating evanescent modes and flow losses into reference impedances in
      acoustic Thevenin calibration.
AB  - This paper proposes an alternative approach to acoustic Thevenin calibration of
      an ear probe. An existing methodology derives the Thevenin-equivalent source
      parameters from the measured probe pressures in a number of short waveguides by
      solving an overdetermined system of equations. This existing methodology is
      affected by errors caused by evanescent modes when the waveguide model lengths
      are estimated. These errors introduce a parallel acoustic compliance into the
      source parameters. The proposed methodology takes into account evanescent modes
      and flow losses in the transition between the probe tube and waveguides during
      calibration. This is achieved by positioning the probe tube, without an ear tip,
      flush with the input plane in waveguides of well-defined dimensions and utilizing
      the physical rather than estimated lengths to calculate the analytical waveguide
      models. Terms that model evanescent modes and flow losses are added to the plane
      wave impedance and adjusted to minimize the calibration error. It is shown that
      this method can reduce the calibration error across a wide frequency range and
      remove the parallel compliance from the source parameters. This approach leads to
      an independence of the source parameters on the calibration waveguide radius,
      though subsequent impedance measurements are still affected by evanescent modes.

PMID- 29195469
TI  - Comparison of a target-equalization-cancellation approach and a localization
      approach to source separation.
AB  - Interaural differences are important for listeners to be able to maintain focus
      on a sound source of interest in the presence of multiple sources. Because
      interaural differences are sound localization cues, most binaural-cue-based
      source separation algorithms attempt separation by localizing each time-frequency
      (T-F) unit to one of the possible source directions using interaural differences.
      By assembling T-F units that are assigned to one direction, the sound stream from
      that direction is enhanced. In this paper, a different type of binaural cue for
      source-separation purposes is proposed. For each T-F unit, the target-direction
      signal is cancelled by applying the equalization-cancellation (EC) operation to
      cancel the signal from the target direction; then, the dominance of the target in
      each T-F unit is determined by the effectiveness of the cancellation.
      Specifically, the energy change from cancellation is used as the criterion for
      target dominance for each T-F unit. Source-separation performance using the
      target-EC cue is compared with performance using localization cues. With
      simulated multi-talker and diffuse-babble interferers, the algorithm based on
      target-EC cues yields better source-separation performance than the algorithm
      based on localization cues, both in direct comparison with the ideal binary mask
      and in measured speech intelligibility for the separated target streams.

PMID- 29195470
TI  - Acoustic occurrence detection of a newly recorded Indo-Pacific humpback dolphin
      population in waters southwest of Hainan Island, China.
AB  - In 2014, Indo-Pacific humpback dolphins were recorded for the first time in
      waters southwest of Hainan Island, China. In this paper, the temporal occurrence
      of Indo-Pacific humpback dolphins in this region was detected by stationary
      passive acoustic monitoring. During the 130-day observation period (from January
      to July 2016), 1969 click trains produced by Indo-Pacific humpback dolphins were
      identified, and 262 ten-minute recording bins contained echolocation click trains
      of dolphins, of which 70.9% were at night and 29.1% were during the day. A
      diurnal rhythm with a nighttime peak in acoustic detections was found. Passive
      acoustic detections indicated that the Indo-Pacific humpback dolphins frequently
      occurred in this area and were detected mainly at night. This information may be
      relevant to conservation efforts for these dolphins in the near future.

PMID- 29195471
TI  - Analysis of the transient surface wave propagation in soft-solid elastic plates.
AB  - In dynamic elastography, the goal is to estimate the Young's modulus from audio
      frequency wave propagation in soft-tissues. Within this frequency range, the
      shear wavelength is centimeter-sized while the compressional wavelength is meter
      sized. Thus, the experimental data are usually collected in the near-field of the
      source. Near-field effects have been widely studied for bulk wave propagation.
      However, the near- and transient-fields of surface and guided waves have received
      less attention. In this work, the transient surface displacement field in soft
      solid elastic plates in vacuum is analyzed. Due to the high Poisson's ratio, mode
      conversion has special characteristics in soft-solids. They are analyzed through
      this work where it is shown that the transient-field over the surface can be
      interpreted by tracing a few reflections. The authors show the existence of a
      critical distance needed for the formation of Rayleigh-Lamb modes. Below this
      distance, only direct surface waves propagate without contribution from reflected
      waves. Thus, the dispersion curve differs from that predicted by Rayleigh-Lamb
      modes. Instead, the authors propose a model based on the interference of surface
      waves, which agree with the experimental data. In addition, the conditions needed
      in order to retrieve the shear wave phase velocity from the surface field are
      given.

PMID- 29195472
TI  - Simulating alveolar trills using a two-mass model of the tongue tip.
AB  - This paper investigates the possibility of reproducing the self-sustained
      oscillation of the tongue tip in alveolar trills. The interest is to study the
      articulatory and phonatory configurations that are required to produce alveolar
      trills. Using a realistic geometry of the vocal tract, derived from cineMRI data
      of a real speaker, the paper studies the mechanical behavior of a lumped two-mass
      model of the tongue tip. Then, the paper proposes a solution to simulate the
      incomplete occlusion of the vocal tract during linguopalatal contacts by adding a
      lateral acoustic waveguide. Finally, the simulation framework is used to study
      the impact of a set of parameters on the characteristic features of the produced
      alveolar trills. It shows that the production of trills is favored when the
      distance between the equilibrium position of the tongue tip and the hard palate
      in the alveolar zone is less than 1 mm, but without linguopalatal contact, and
      when the glottis is fully adducted.

PMID- 29195473
TI  - Clustering dynamics of microbubbles exposed to low-pressure 1-MHz ultrasound.
AB  - Ultrasound-driven microbubbles have been used in therapeutic applications to
      deliver drugs across capillaries and into cells or to dissolve blood clots. Yet
      the performance and safety of these applications have been difficult to control.
      Microbubbles exposed to ultrasound not only volumetrically oscillate, but also
      move due to acoustic radiation, or Bjerknes, forces. The purpose of this work was
      to understand the extent to which microbubbles moved and clustered due to
      secondary Bjerknes forces. A microbubble population was exposed to a 1-MHz
      ultrasound pulse with a peak-rarefactional pressure of 50-100 kPa and a pulse
      length of 20 ms. Microbubbles exposed to low-pressure therapeutic ultrasound were
      observed to cluster at clustering rates of 0.01-0.02 microbubbles per duration
      (in ms) per initial average inter-bubble distance (in MUm), resulting in 1 to 3
      clustered microbubbles per initial average inter-bubble distance (in MUm). Higher
      pressures caused faster clustering rates and a larger number of clustered
      microbubbles. Experimental data revealed clustering time scales, cluster
      localizations, and cluster sizes that were in reasonable agreement with
      simulations using a time-averaged model at low pressures. This study demonstrates
      that clustering of microbubbles occurs within a few milliseconds and is likely to
      influence the distribution of stimuli produced in therapeutic applications.

PMID- 29195474
TI  - Optimal bounds for attenuation of elastic waves in porous fluid-saturated media.
AB  - Explicit expressions for bounds on the effective bulk and shear moduli of mixture
      of an elastic solid and Newtonian fluid are derived. Since in frequency domain
      the shear modulus of the Newtonian fluid is complex valued, the effective mixture
      moduli are, in general, also complex valued and, hence, the bounds are curves in
      the complex plane. From the general expressions for bounds of effective moduli of
      viscoelastic mixtures, it is shown that effective bulk and shear moduli of such
      mixtures must lie between the real axis and a semicircle in the upper half-plane
      connecting formal lower and upper Hashin-Shtrikman bounds of the mixture of the
      solid and inviscid fluid of the same compressibility as the Newtonian fluid.
      Furthermore, it is shown that the bounds on the effective complex bulk and shear
      moduli of the mixture are optimal; that is, the moduli corresponding to any point
      on the bounding curves can be attained by the Hashin sphere assemblage penetrated
      by a random distribution of thin cracks. The results are applicable to a variety
      of solid/fluid mixtures such as fluid-saturated porous materials and particle
      suspensions.

PMID- 29195475
TI  - Measurement of acoustic properties for passive-material samples using
      multichannel inverse filter.
AB  - The measurement of acoustic properties for passive-material samples is strongly
      interfered by reverberations in a limited space. A multichannel inverse filter
      (MIF) can achieve spatio-temporal focusing by retransmitting the optimal signal
      estimated from multichannel impulse responses of the transmitter channel and the
      underwater acoustic channel. To decrease the influence of reverberations on
      measurements and improve the measurement precision, a MIF is employed to measure
      the echo reduction and insertion loss, respectively. The method is demonstrated
      by simulations and experiments, which were performed in a cylindrical tank to
      measure the two acoustic parameters for a steel plate sample.

PMID- 29195476
TI  - Scattering of flexural waves from an N-beam resonator in a thin plate.
AB  - The impedance matrix method is applied to study the scattering of flexural waves
      propagating in an infinite thin plate containing an N-beam resonator. The
      resonator consists of a circular hole containing a smaller plate connected to the
      background plate by a number N of rectangular beams. After representing the
      boundary conditions in a modal multipole expansion form, a compact expression is
      obtained for the T-matrix, which relates the incident and the scattered
      transverse (out-of-plane) waves. The analysis of the scattering cross-section
      reveals interesting scattering features, like resonances and anisotropy,
      associated to this type of resonators. Numerical experiments performed within the
      framework of the finite element method support the accuracy of the model here
      developed.

PMID- 29195477
TI  - Ultrawide band gaps in beams with double-leaf acoustic black hole indentations.
AB  - Band gaps in conventional phononic crystals (PCs) are attractive for applications
      such as vibration control, wave manipulation, and sound absorption. Their
      practical implementations, however, are hampered by several factors, among which
      the large number of cells required and their impractically large size to ensure
      the stopbands at reasonably low frequencies are on the top of the list. This
      paper reports a type of beam carved inside with two double-leaf acoustic black
      hole indentations. By incorporating the local resonance effect and the Bragg
      scattering effect generated by a strengthening stud connecting the two branches
      of the indentations, ultrawide band gaps are achieved. Increasing the length of
      the stud or reducing the residual thickness of the indentation allows the tuning
      of the band gaps to significantly enlarge the band gaps, which can exceed 90% of
      the entire frequency range of interest. Experimental results show that with only
      three cells, the proposed beam allows considerable vibration energy attenuation
      within an ultra-broad frequency range including the low frequency range, which
      conventional PCs can hardly reach. Meanwhile, the proposed configuration also
      enhances the structural integrity, thus pointing at promising applications in
      vibration control and a high performance wave filter design.

PMID- 29195478
TI  - Wave characteristics of a cylinder with periodic ribs.
AB  - This paper deals with wave characteristics of a cylinder with periodic ribs. The
      equation of motion of the stiffened cylinder is first derived using a receptance
      coupling method. The dispersion diagrams of the stiffened cylinder are then
      obtained in order to figure out the effects of the ribs on the wave propagation.
      Due to the effect of the ribs, the dispersion curves are found to be repeated
      along the axis of the wavenumber with the repetition period of 2pi/d, where d is
      the rib distance. Also, dispersion curves are found to show a pass and stop band
      of the waves. The stop bands appeared at the wavenumber of half of the wavenumber
      periodicity. The stop band becomes wider as the increase of the circumferential
      order. The waves in the pass bands are propagating well through the ribs without
      decay. In contrast, the waves in the stop bands are not propagating, but decaying
      the magnitudes. The decay of the responses in the stop band increases as the
      circumferential order increase. The change of the rib stiffness causes the cut-on
      frequency to change and the modal order to jumble. The change of the rib
      stiffness also leads to generate a wave whose phase velocity is positive, while
      group velocity is negative.

PMID- 29195479
TI  - Level-weighted averaging in elevation to synchronous amplitude-modulated sounds.
AB  - To program a goal-directed response in the presence of multiple sounds, the
      audiomotor system should separate the sound sources. The authors examined whether
      the brain can segregate synchronous broadband sounds in the midsagittal plane,
      using amplitude modulations as an acoustic discrimination cue. To succeed in this
      task, the brain has to use pinna-induced spectral-shape cues and temporal
      envelope information. The authors tested spatial segregation performance in the
      midsagittal plane in two paradigms in which human listeners were required to
      localize, or distinguish, a target amplitude-modulated broadband sound when a non
      modulated broadband distractor was played simultaneously at another location. The
      level difference between the amplitude-modulated and distractor stimuli was
      systematically varied, as well as the modulation frequency of the target sound.
      The authors found that participants were unable to segregate, or localize, the
      synchronous sounds. Instead, they invariably responded toward a level-weighted
      average of both sound locations, irrespective of the modulation frequency. An
      increased variance in the response distributions for double sounds of equal level
      was also observed, which cannot be accounted for by a segregation model, or by a
      probabilistic averaging model.

PMID- 29195480
TI  - Scattering of a longitudinal Bessel beam by a sphere embedded in an isotropic
      elastic solid.
AB  - The scattering of a longitudinal Bessel beam of arbitrary order by a sphere
      embedded in an isotropic solid matrix is theoretically analyzed. The spherical
      inclusion can be made of a viscoelastic, elastic, or fluid-filled isotropic
      material. In the analysis, the absorbing, scattering, and extinction efficiency
      factors are obtained, e.g., the corresponding power per characteristic beam
      intensity per sphere's cross-section area. Furthermore, the extended optical
      theorem, which expresses the extinction efficiency in terms of an integral of the
      longitudinal scattering function is derived. Several features of zeroth- and
      first-order Bessel beams scattering in solids are illustrated considering a
      polymer adhesive (cured) sphere embedded in a stainless steel matrix. For
      instance, omnidirectional scattering can be achieved by choosing specific values
      of the half-cone angle of the Bessel beam, which is the beam's geometrical
      parameter. Additionally, it is demonstrated that mode suppression leads to lower
      absorption inside the inclusion when compared to plane wave scattering results.

PMID- 29195481
TI  - Underwater vocal complexity of Arctic seal Erignathus barbatus in Kongsfjorden
      (Svalbard).
AB  - In this study the description of underwater vocal repertoire of bearded seal in
      Svalbard (Norway) was extended. Two autonomous passive acoustic recorders were
      deployed for one year (August 2014-July 2015) in the inner and outer parts of the
      Kongsfjorden, and 1728 h were recorded and 17 220 vocalizations were found. Nine
      different vocalization classes were identified and characterized using ten
      acoustic parameters. The calls showed heterogeneous spectral features, but share
      the descending trend of frequency modulation. The different classes emerged were
      discriminated primarily by bandwidth and duration, and then by minimum frequency,
      central frequency, and maximum frequency in this order. This study represents a
      step forward to improve the understanding of the acoustic behaviour and the
      social function of these calls, and identified long passive acoustic monitoring
      as an effective method to assess vocal complexity and the ecology of marine
      species producing sounds.

PMID- 29195483
TI  - Temporal characteristics of contextual effects in sound localization.
AB  - Two experiments examined plasticity induced by context in a simple target
      localization task. The context was represented by interleaved localization trials
      with the target preceded by a distractor. In a previous study, the context
      induced large response shifts when the target and distractor stimuli were
      identical 2-ms-noise clicks [Kopco, Best, and Shinn-Cunningham (2007). J. Acoust.
      Soc. Am. 121, 420-432]. Here, the temporal characteristics of the contextual
      effect were examined for the same stimuli. Experiment 1 manipulated the context
      presentation rate and the distractor-target inter-stimulus interval (ISI).
      Experiment 2 manipulated the temporal structure of the context stimulus,
      replacing the one-click distractor either by a distractor consisting of eight
      sequentially presented clicks or by a noise burst with total energy and duration
      identical to the eight-click distractor. In experiment 1, the contextual shift
      size increased with increasing context rate while being largely independent of
      ISI. In experiment 2, the eight-click-distractor induced a stronger shift than
      the one-click-distractor context, while the noise-distractor context induced a
      very small shift. These results suggest that contextual plasticity is an
      adaptation driven both by low-level factors like spatiotemporal context
      distribution and higher-level factors like perceptual similarity between the
      stimuli, possibly related to precedence buildup.

PMID- 29195482
TI  - The effects of varying tympanic-membrane material properties on human middle-ear
      sound transmission in a three-dimensional finite-element model.
AB  - An anatomically based three-dimensional finite-element human middle-ear (ME)
      model is used to test the sensitivity of ME sound transmission to tympanic
      membrane (TM) material properties. The baseline properties produce responses
      comparable to published measurements of ear-canal input impedance and power
      reflectance, stapes velocity normalized by ear-canal pressure (PEC), and middle
      ear pressure gain (MEG), i.e., cochlear-vestibule pressure (PV) normalized by
      PEC. The mass, Young's modulus (ETM), and shear modulus (GTM) of the TM are
      varied, independently and in combination, over a wide range of values, with soft
      and bony TM-annulus boundary conditions. MEG is recomputed and plotted for each
      case, along with summaries of the magnitude and group-delay deviations from the
      baseline over low (below 0.75 kHz), mid (0.75-5 kHz), and high (above 5 kHz)
      frequencies. The MEG magnitude varies inversely with increasing TM mass at high
      frequencies. Increasing ETM boosts high frequencies and attenuates low and mid
      frequencies, especially with a bony TM annulus and when GTM varies in proportion
      to ETM, as for an isotropic material. Increasing GTM on its own attenuates low
      and mid frequencies and boosts high frequencies. The sensitivity of MEG to TM
      material properties has implications for model development and the interpretation
      of experimental observations.

PMID- 29195484
TI  - Targeted delivery of garcinia glycosides by reconstituted high-density
      lipoprotein nano-complexes.
AB  - Scavenger receptor class B type 1 (SR-B1) is over-expressed in tumour cells where
      it mediates the uptake of drug payload of reconstituted high density lipoprotein
      (rHDL) via the process of reverse cholesterol transport. In this study, rHDL was
      prepared to determine its function as a drug delivery carrier for targeting
      hepatocellular carcinoma by incorporating the anti-tumour drug garcinia
      glycosides (GG) into rHDL to yield rHDL/GG nano-complexes. Structural analysis
      indicated that the rHDL/GG nano-complex was similar to HDL in size. HepG2 cells
      treated with fluorescent-labelled rHDL/GG exhibited a time-dependent increase in
      cell death. Further experiment in which HepG2 cells were treated with rHDL/GG
      plus plasma-derived HDL showed reduction in cell death compared to treatment with
      rHDL/GG alone, suggesting that plasma-derived HDL compete with rHDL/GG for
      binding to the SR-B1 on the cell. We concluded that rHDL could not only
      incorporate GG but could also serve as a carrier, targeting the drug to HepG2
      cells via SR-B1.

PMID- 29195485
TI  - Post-allograft relapse of acute lymphoblastic leukemia: rational use of the new
      targeted therapies.

PMID- 29195486
TI  - A safety review of the medications used to treat atopic dermatitis.
AB  - INTRODUCTION: Atopic dermatitis (AD) is a common disease in children and adults
      which causes severe physical discomfort and psychosocial distress. Recently novel
      therapies for AD have been FDA approved for use which creates the need to review
      the safety surrounding current FDA approved AD medications. Areas covered:
      Published clinical studies involving topical and oral FDA approved medications
      for AD are included in this review. Authors used PubMed research database to
      search for clinical trials involving AD patients. Expert opinion: AD is a common
      disease which currently has limited FDA approved medications. Given the
      chronicity of this disease, medications are needed which control disease while
      minimizing side effects to allow for long term use. Newer approved medications
      show promise but safety data is limited given their relatively new utilization
      for AD.

PMID- 29195487
TI  - Efficacy of levomilnacipran extended release in treating major depressive
      disorder.
AB  - INTRODUCTION: Major depressive disorder (MDD) is the leading cause of disability
      worldwide with a heterogeneous symptom profile. Levomilnacipran extended release
      (ER) (Fetzima), a SNRI, has been approved by the Food and Drug Administration for
      treatment of MDD. While categorized as a SNRI, in contradistinction to other
      approved SNRIs, levomilnacipran exhibits differential affinity for the
      norepinephrine reuptake transporter when compared to the serotonin reuptake
      transporter. Areas covered: Completed clinical trials which focused on
      levomilnacipran ER administered in those with MDD were included in this drug
      evaluation. Expert opinion: Levomilnacipran ER, like all other first-line
      antidepressants exhibits significant efficacy in reducing total symptom severity.
      Levomilnacipran ER is particularly effective at improving measures of motivation,
      energy, and interest. Head to head comparative trials are not available with
      other antidepressants, and consequently, there are no claims of superior efficacy
      when compared to alternative antidepressants. Notwithstanding, it would be a
      viable and testable hypothesis that differential efficacy in favor of
      levomilnacipran may be obtained across select dimensions of depressive symptoms
      (e.g., fatigue and lack of motivation). Unfortunately, rigorous studies
      evaluating levomilnacipran for cognitive function in MDD have not been conducted.
      Levomilnacipran ER is generally well tolerated with minimal propensity for
      metabolic and weight disturbance.

PMID- 29195488
TI  - Improving the attrition rate of Lanthipeptide discovery for commercial
      applications.
AB  - INTRODUCTION: Lanthipeptides are a class of ribosomally synthesized and post
      translationally modified peptides. Lanthipeptides with antimicrobial activity are
      referred to as lantibiotics. Lantibiotics are generally active against Gram
      positive bacteria. However, some modifications have expanded their activity
      toward Gram-negative bacteria. Furthermore, additional functions aside from
      antibacterial activities have been reported for lanthipeptides. Areas covered:
      This review provides a synopsis of current anthipeptide research for potential
      therapeutics. The review highlights the current tools used for identifying
      lanthipeptides from genomic sequencing data. It also describes the current
      approaches that have been used to overcome the limitations in the purification
      and isolation of lanthipeptides. The status of lanthipeptides in terms of
      potential applications and approaches that are currently being done to promote
      the development of lanthipeptides as novel therapeutics are also discussed.
      Expert opinion: Significant improvements have been made to promote the discovery
      of new lanthipeptides, while, simultaneously, tools have been developed to
      promote their production and isolation. Lanthipeptides are showing significant
      promise for treating bacterial infections, as well as for new applications as
      anticancer and antiviral agents, or as a novel treatment for pain management. At
      the current rate of lanthipeptide discovery and isolation of the products, it is
      likely several new applications will be discovered.

PMID- 29195490
TI  - Marginal decision-making in the treatment of refractory epilepsy.
AB  - OBJECTIVE: Epilepsy surgery is one of the most effective treatments in modern
      medicine. Yet, it remains largely under-utilized, in spite of its proven
      efficacy. The referrals for epilepsy surgery are often delayed until it is too
      late to prevent the detrimental psychosocial effects of refractory seizures. The
      reluctance towards epilepsy surgery is influenced by the perceived risks of the
      procedure by practitioners and patients. This review discusses how, in general
      decision-making processes, one faces a natural tendency towards emphasizing the
      risks of the most immediate and operational decision (surgery), at times without
      contrasting these risks with the alternative (uncontrolled epilepsy). METHODS: In
      the field of economics, this bias is well recognized and can be overcome through
      marginal analysis, formally defined as focusing on incremental changes as opposed
      to absolute levels. RESULTS: Regarding epilepsy surgery, the risks and benefits
      of surgery are considered separately from the risks of uncontrolled epilepsy. For
      instance, even though surgery carries an ~0.1-0.5% risk of perioperative
      mortality, the chance of sudden unexpected death with refractory epilepsy can be
      as high as 0.6-0.9% per year. It is suggested that the inadequate way of phrasing
      clinical questions can be a crucial contributing factor for the under-utilization
      of epilepsy surgery. SIGNIFICANCE: It is proposed that examining decision-making
      for epilepsy surgery in the context of marginal analysis may enable providers and
      patients to make more accurate informed decisions.

PMID- 29195489
TI  - Secondary sex ratio in relation to exposures to polychlorinated biphenyls,
      dichlorodiphenyl dichloroethylene and methylmercury.
AB  - This study was undertaken to assess the potential impact of maternal exposures to
      polychlorinated biphenyl (PCB), dichlorodiphenyl dichloroethylene (DDE) and
      methylmercury on the secondary sex ratios (the ratio of male to female live
      births) over a span of 23 years. The study includes prospective data from three
      Faroese birth cohorts, with a total of 2,152 healthy mother-child dyads recruited
      between 1986 and 2009. The Faroe Islands is a subarctic fishing community, where
      pilot whale meat and blubber are part of the traditional marine diet. Exposures
      were measured in maternal hair, serum or umbilical cord blood. Confounder
      adjusted logistic regression models were used to assess the associations between
      maternal exposures and the secondary sex ratio. A doubling in SigmaPCB, p,p'-DDE
      and mercury concentrations were associated with increased odds by 8% (95% CI = 0
      16%), 7% (95% CI = 0-14%) and 9% (95% CI = 2-17%), respectively, of giving birth
      to a boy. In conclusion, maternal exposure to SigmaPCB, DDE and methylmercury was
      associated with a slightly increased secondary sex ratio. The impact of paternal
      exposures could not be taken into account and deserves attention.

PMID- 29195491
TI  - ROS-mediated heme degradation and cytotoxicity induced by iron nanoparticles:
      hemoglobin and lymphocyte cells as targets.
AB  - Nanoparticles (NPs) due to their small size and high surface area induce
      remarkable adverse effects on the biological systems. However, the exact
      mechanism by which NPs interacted with biological system and induce their adverse
      effects is still an enigma. Herein, the interaction of zero valent iron NPs (ZVFe
      NPs) with human hemoglobin (Hb) was evaluated using a variety of techniques
      including circular dichroism, fluorescence, and UV-visible (UV-vis) spectroscopy
      methods. Also, the cytotoxicity of ZVFe NPs on the human lymphocyte cell line as
      a model of blood system cell line was investigated by reactive oxygen species
      (ROS), caspase-9, and caspase-3 activities assays. It was revealed that ZVFe NP
      interaction resulted in heme displacement and degradation and induction of
      protein cabonylation. It was also shown that ZVFe NPs impaired the complexity of
      lymphocyte cells through ROS generation and apoptotic pathway. Together, these
      data suggest that NPs influence the biological system and induce adverse effects
      through ROS generation.

PMID- 29195492
TI  - Correction to: Exposure to a community-wide campaign is associated with physical
      activity and sedentary behavior among Hispanic adults on the Texas-Mexico border.
AB  - CORRECTION: After publication of the article [1], it has been brought to our
      attention that there is an acknowledgement missing. The authors would like to add
      the following - "The authors would like to thank the staff and community partners
      who work to implement the activities of the community wide campaign. In
      particular we would like to thank Lisa Mitchell-Bennett, Vanessa Saldana,
      Jennifer Mota, Sister Phylis Peters and the team of community health workers at
      UT Health and Proyecto Juan Diego who were involved in planning and gathering
      data."

PMID- 29195493
TI  - Adiponectin, biomarkers of inflammation and changes in cardiac autonomic
      function: Whitehall II study.
AB  - BACKGROUND: Biomarkers of inflammation and adiponectin are associated with
      cardiovascular autonomic neuropathy (CAN) in cross-sectional studies, but
      prospective data are scarce. This study aimed to assess the associations of
      biomarkers of subclinical inflammation and adiponectin with subsequent changes in
      heart rate (HR) and heart rate variability (HRV) in non-diabetic and diabetic
      individuals. METHODS: Data are based on up to 25,050 person-examinations for 8469
      study participants of the Whitehall II cohort study. Measures of CAN included HR
      and several HRV indices. Associations between baseline serum levels of high
      sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-1 receptor
      antagonist (IL-1Ra) and adiponectin and 5-year changes in HR and six HRV indices
      were estimated using mixed-effects models adjusting for age, sex, ethnicity, body
      mass index (BMI), metabolic covariates and medication. A modifying effect of
      diabetes was tested. RESULTS: Higher levels of IL-1Ra were associated with higher
      increases in HR. Additional associations with measures of HRV were observed for
      hsCRP, IL-6 and IL-1Ra, but these associations were explained by BMI and other
      confounders. Associations between adiponectin, HR and HRV differed depending on
      diabetes status. Higher adiponectin levels were associated with more pronounced
      decreases in HR and increases in three measures of HRV reflecting both
      sympathetic and vagal activity, but these findings were limited to individuals
      with type 2 diabetes. CONCLUSIONS: Higher IL-1Ra levels appeared as novel risk
      marker for increases in HR. Higher adiponectin levels were associated with a more
      favourable development of cardiovascular autonomic function in individuals with
      type 2 diabetes independently of multiple confounders.

PMID- 29195494
TI  - Implementation of a workplace intervention using financial rewards to promote
      adherence to physical activity guidelines: a feasibility study.
AB  - BACKGROUND: We designed and implemented the Brigham and Women's Wellness
      Initiative (B-Well), a single-arm study to examine the feasibility of a workplace
      program that used individual and team-based financial incentives to increase
      physical activity among sedentary hospital employees. METHODS: We enrolled
      sedentary, non-clinician employees of a tertiary medical center who self-reported
      low physical activity. Eligible participants formed or joined teams of three
      members and wore Fitbit Flex activity monitors for two pre-intervention weeks
      followed by 24 weeks during which they could earn monetary rewards. Participants
      were rewarded for increasing their moderate-to-vigorous physical activity (MVPA)
      by 10% from the previous week or for meeting the Centers for Disease Control and
      Prevention (CDC) physical activity guidelines (150 min of MVPA per week). Our
      primary outcome was the proportion of participants meeting weekly MVPA goals and
      CDC physical activity guidelines. Secondary outcomes included Fitbit-wear
      adherence and factors associated with meeting CDC guidelines more consistently.
      RESULTS: B-Well included 292 hospital employees. Participants had a mean age of
      38 years (SD 11), 83% were female, 38% were obese, and 62% were non-Hispanic
      White. Sixty-three percent of participants wore the Fitbit >=4 days per week for
      >=20 weeks. Two-thirds were satisfied with the B-Well program, with 79%
      indicating that they would participate again. Eighty-six percent met either their
      personal weekly goal or CDC physical activity guidelines for at least 6 out of 24
      weeks, and 52% met their goals or CDC physical activity guidelines for at least
      12 weeks. African Americans, non-obese subjects, and those with lower impulsivity
      scores reached CDC guidelines more consistently. CONCLUSIONS: Our data suggest
      that a financial incentives-based workplace wellness program can increase MVPA
      among sedentary employees. These results should be reproduced in a randomized
      controlled trial. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02850094 .
      Registered July 27, 2016 [retrospectively registered].

PMID- 29195495
TI  - The effectiveness of vibrational stimulus to accelerate orthodontic tooth
      movement: a systematic review.
AB  - BACKGROUND: In recent years, it has been a hot research topic to accelerate
      orthodontic tooth movement (OTM) through vibration. This review was therefore
      aimed to systematically evaluate the available evidences on the efficacy of
      vibrational stimulus to accelerate OTM. METHODS: Randomized controlled trials and
      controlled clinical trials that evaluated the efficacy of vibration on OTM
      acceleration were searched through electronic and manual search. Two review
      authors independently conducted the study inclusion, quality assessment and data
      extraction. The quality of synthesized evidence was assessed according to GRADE
      system. RESULTS: Eight clinical trials were included in this systematic review.
      Four studies found that vibration did not enhance the rate of OTM during
      alignment phase. Two studies revealed that the use of vibratory stimulation
      accelerated canine retraction. No deleterious effects including pain perceptions
      and root resorptions were reported. CONCLUSIONS: Within the limitations of this
      review, weak evidence indicates that vibrational stimulus is effective for
      accelerating canine retraction but not for alignment. The effects of vibration on
      pain intensity and root resorption during orthodontic treatment are inconclusive.
      Future high-quality clinical trials are needed before warranting recommendations
      to clinical application.

PMID- 29195496
TI  - "Does the Salmonella Genomic Island 1 (SGI1) confer invasiveness properties to
      human isolates?"
AB  - BACKGROUND: In the eighties, a multidrug resistant clone of Salmonella
      Typhimurium DT104 emerged in UK and disseminated worldwide. This clone harbored a
      Salmonella genomic island 1 (SGI1) that consists of a backbone and a multidrug
      resistant region encoding for penta-resistance (ampicillin,
      chloramphenicol/florfenicol, streptomycin/spectinomycin, sulphonamides and
      tetracycline (ACSSuT)). Several authors suggested that SGI1 might have a
      potential role in enhancement of virulence properties of Salmonella enterica. The
      aim of this study was to investigate whether nontyphoidal S. enterica isolates
      carrying SGI1 cause more severe illness than SGI1 free ones in humans. METHODS:
      From 2011 to 2016, all patients infected with nontyphoidal S. enterica in our
      hospital were retrospectively included. All nontyphoidal S. enterica isolates
      preserved in our University Hospital (Dijon, France) were screened for the
      presence of SGI1. Clinical and biological data of patients were retrospectively
      collected to evaluate illness severity. Statistical analysis of data was
      performed by Kruskal-Wallis test or Fisher's exact test for univariate analysis,
      and by logistic regression for multivariate analysis. RESULTS: A total of 100
      isolates of S. enterica (22 serovars) were collected. Twelve isolates (12%)
      belonging to 4 serovars harbored SGI1: S. Typhimurium, S. Infantis, S. Kentucky,
      S. St Paul. The severity of the disease was age-related (for invasive infection,
      sepsis and inflammatory response) and was associated with immunosuppression (for
      invasive infection, sepsis and bacteremia) but not with the presence of SGI1 or
      with antimicrobial resistance. CONCLUSION: A rather high proportion (12%) of
      human clinical isolates belonging to various serovars (for the first time serovar
      St Paul) and harboring various antimicrobial resistance profile carried SGI1.
      Diseases due to SGI1-positive S. enterica or to antimicrobial resistant isolates
      were not more severe than the others. This first clinical observation should be
      confirmed by a multicenter and prospective study.

PMID- 29195497
TI  - Bilateral uveitis and macular edema induced by Nivolumab: a case report.
AB  - BACKGROUND: Nivolumab is a fully human antibody which is routinely used at first
      therapy for metastatic melanoma. Usually, side effects are immune-related adverse
      events. We report a case of a man who developed bilateral anterior uveitis and
      macular serous retinal detachment during nivolumab treatment for metastatic
      melanoma. CASE PRESENTATION: A man on nivolumab treatment for a leg melanoma with
      duodenal and lymph nodes metastases developed a sudden bilateral visual acuity
      impairment and bilateral non-painfull redness eyes several days after the third
      infusion. The clinical examination showed a significant decreased of the visual
      acuity. Slit lamp examination revealed the presence of bilateral granulomatous
      keratic precipitates, anterior chamber cells +++, bilateral synechiae, bilateral
      papilledema and macular edema associated with serous retinal detachment in the
      left eye. The anti-Programmed cells Death-1 was stopped and a topical
      corticosteroid treatment was administrated. After 8 days of topical
      corticosteroid treatment visual acuity was worsening with similar optical
      coherence tomography examination. An oral corticosteroid treatment was started.
      Evolution was favorable with a decrease of ocular inflammation and a complete
      visual acuity recovery after 3 weeks. Nivolumab was re-initiated. CONCLUSIONS:
      This is the second clinical report of bilateral anterior uveitis associated with
      macular serous retinal detachment related to anti-PD-1 treatment, and the first
      with nivolumab. Cases of uveitis were reported several times. Although rare,
      ophthalmologic manifestations that are rapidly recognized and adequately managed
      can be treated.

PMID- 29195498
TI  - Correction to: Risk management of emergency service vehicle crashes in the United
      States fire service: process, outputs, and recommendations.
AB  - CORRECTION: After publication of the article [1], it has been brought to our
      attention that the second author's name was published incorrectly. Previously
      included as "Keshia P. Porter", the full and correct name should be "Keshia
      Pollack Porter". This has now been corrected in the original version of the
      article.

PMID- 29195499
TI  - Adjuvant chemotherapy improves survival of patients with high-risk upper urinary
      tract urothelial carcinoma: a propensity score-matched analysis.
AB  - BACKGROUND: The purposes of this study were to determine whether adjuvant
      chemotherapy (AC) improved the prognosis of patients with high-risk upper urinary
      tract urothelial carcinoma (UTUC)and to identify the patients who benefited from
      AC. METHODS: Among a multi-center database of 1014 patients who underwent RNU for
      UTUC, 344 patients with >= pT3 or the presence of lymphovascular invasion (LVI)
      were included. Cancer-specific survival (CSS) estimates were calculated by the
      Kaplan-Meier method, and groups were compared by the log-rank test. Each
      patient's probability of receiving AC depending on the covariates in each group
      was estimated by logistic regression models. Propensity score matching was used
      to adjust the confounding factors for selecting patients for AC, and log-rank
      tests were applied to these propensity score-matched cohorts. Cox proportional
      hazards regression modeling was used to identify the variables with significant
      interaction with AC. Variables included age, pT category, LVI, tumor grade, ECOG
      performance status and low sodium or hemoglobin score, which we reported to be a
      prognostic factor of UTUC. RESULTS: Of the 344 patients, 241 (70%) had received
      RNU only and 103 (30%) had received RNU+AC. The median follow-up period was 32
      (range 1-184) months. Overall, AC did not improve CSS (P = 0.12). After
      propensity score matching, the 5-year CSS was 69.0% in patients with RNU+AC
      versus 58.9% in patients with RNU alone (P = 0.030). Subgroup analyses of
      survival were performed to identify the patients who benefitted from AC.
      Subgroups of patients with low preoperative serum sodium (<= 140 mEq/ml) or
      hemoglobin levels below the normal limit benefitted from AC (HR 0.34, 95% CI 0.15
      0.61, P = 0.001). In the subgroup of patients with normal sodium and normal
      hemoglobin levels, 5-year CSS was 77.7% in patients with RNU+AC versus 80.2% in
      patients with RNU alone (P = 0.84). In contrast, in the subgroup of patients with
      low sodium or low hemoglobin levels, 5-year CSS was 71.0% in patients with RNU+AC
      versus 38.5% in patients with RNU alone (P < 0.001). CONCLUSIONS: High-risk UTUC
      patients, especially subgroups of patients with lower sodium and hemoglobin
      levels, could benefit from AC after RNU.

PMID- 29195500
TI  - An implantable pump Lenus pro(r) in the treatment of pulmonary arterial
      hypertension with intravenous treprostinil.
AB  - BACKGROUND: Subcutaneous treprostinil is a prostacyclin analogue used to treat
      pulmonary arterial hypertension (PAH). Due to local pain it can cause a
      deterioration of heart related quality of life (HRQoL) or even abandonment of
      treatment. The aim of this paper was to assess the feasibility of treatment with
      intravenous treprostinil administered by means of the Lenus Pro(r) implantable
      pump. METHODS: This was a retrospective, multi-center study involving 12 patients
      (8 females) with PAH treated with a subcutaneous infusion of treprostinil with
      intolerable pain at the infusion site. Clinical evaluation, including HRQoL
      assessment with SF-36 questionnaire was performed, before pump implantation and 2
      9 months after. The median time of follow-up time was 14 months (4-29 months).
      RESULTS: After implantation of the Lenus Pro(r) pump, no statistically
      significant changes were observed in the 6-min walking distance and NT-proBNP.
      After implantation 50% of patients were in II WHO functional class (33% before, p
      = 0,59). There was a significant improvement in HRQoL within the Physical
      Component Score (28 +/- 7 vs 38 +/- 8 pts., p < 0,001) and in specific domains of
      SF-36 form: physical role (31 +/- 7 pts. vs. 41 +/- 12 pts., p = 0,03), bodily
      pain (31 +/- 12 vs. 50 +/- 14 pts., p = 0,02), and vitality (37 +/- 8 pts. vs. 50
      +/- 14 pts., p = 0,03). During the periprocedural period, one patient developed a
      recurrent haematoma at the implantation site. During follow-up in one patient,
      the drug delivering cannula slipped out of the subclavian vein, what required
      repositioning repeated twice, and in another patient an unexpected increase in
      the drug administration rate was observed. CONCLUSIONS: In patients with PAH who
      do not tolerate subcutaneous infusion of treprostinil, the use of the Lenus
      Pro(r) implantable pump results in significant subjective improvement of vitality
      and physical aspect of the HRQoL with acceptable safety profile.

PMID- 29195501
TI  - COMT genotype and non-recovery after a whiplash injury in a Northern European
      population.
AB  - BACKGROUND: The COMT (Catechol-O-Methyl Transferase) gene may influence a
      person's vulnerability to develop long-term pain and some COMT single nucleotide
      polymorphisms (SNPs) may associate with patterns of acute or chronic pain. Many
      patients with whiplash-associated disorders (WADs) suffer from long-term pain and
      other related symptoms, but it is less known if genetic factors play a role in
      the recovery process. The primary aim of this study was to evaluate whether self
      reported non-recovery, including pain, was related to COMT genotype in patients
      with WAD. The secondary aim was to investigate whether or not background factors,
      including mental health, were related to genotype and non-recovery. METHODS: A
      total of 133 patients with neck pain after a whiplash trauma were included.
      Background factors were collected and blood samples were taken during the acute
      phase after the accident. DNA was isolated from blood and used to genotype the
      SNPs rs6269, rs4633, rs4818 and rs4680 in the COMT gene; additionally haplotypes
      were estimated and haplogenotypes inferred. The patients were followed up after
      12 months and asked to rate their recovery including pain, mental health and
      quality of life. RESULTS: The overall reported non-recovery rate at 12 months was
      44% with no significant differences in distribution of the COMT haplotypes. High
      levels of self-reported pain (OR 7.2) and anxiety (OR 4.4) after the accident
      were associated with non-recovery, but not related to the haplotypes. None of the
      other background factors were related to the haplotypes or non-recovery.
      CONCLUSION: No association between self-reported non-recovery or pain levels and
      COMT haplotypes in patients with acute whiplash injuries could be detected.
      Independent replications are necessary to discard the hypothesis that COMT
      haplotypes do not influence non-recovery or pain levels in patients with acute
      whiplash injuries. High levels of initial pain and anxiety were associated with
      non-recovery, thereby confirming previously published reports.

PMID- 29195502
TI  - OMSV enables accurate and comprehensive identification of large structural
      variations from nanochannel-based single-molecule optical maps.
AB  - We present a new method, OMSV, for accurately and comprehensively identifying
      structural variations (SVs) from optical maps. OMSV detects both homozygous and
      heterozygous SVs, SVs of various types and sizes, and SVs with or without
      creating or destroying restriction sites. We show that OMSV has high sensitivity
      and specificity, with clear performance gains over the latest method. Applying
      OMSV to a human cell line, we identified hundreds of SVs >2 kbp, with 68 % of
      them missed by sequencing-based callers. Independent experimental validation
      confirmed the high accuracy of these SVs. The OMSV software is available at
      http://yiplab.cse.cuhk.edu.hk/omsv/ .

PMID- 29195503
TI  - Recent development in clinical applications of PD-1 and PD-L1 antibodies for
      cancer immunotherapy.
AB  - Antibodies against programmed death (PD) pathway are revolutionizing cancer
      immunotherapy. Currently five antibodies against PD-1/PD-L1 have been approved.
      The clinical use of these antibodies is rapidly expanding. Incorporation of PD
      antibodies into chemotherapy regimens is in active clinical investigations. The
      combination of pembrolizumab with carboplatin and pemetrexed has been approved
      for the first line therapy of metastatic non-squamous non-small cell lung cancer.
      Combination of PD-1/PD-L1 antibodies with small molecule inhibitors such as
      tyrosine kinase inhibitors and IDO inhibitors are in active clinical trials. This
      review summarized recent development in clinical trials of PD-1 and PD-L1
      antibodies for cancer immunotherapy.

PMID- 29195504
TI  - Blinded by Zika? A missed HIV diagnosis that resulted in optic neuropathy and
      blindness: a case report.
AB  - BACKGROUND: Typical symptoms of an acute human immunodeficiency virus (HIV)
      infections like fever and rash are not specific and can be caused by a multitude
      of other pathogens, such as Zika or rickettsiosis. Up to 30% of primary HIV
      infection do not present with the typical flu-like symptoms and thus represent a
      diagnostic challenge. In this report, we describe a rare case of optic neuropathy
      as the initial presentation of primary HIV infection, which resulted in
      irreversible blindness. To our knowledge, only four cases of optic neuropathy
      resulting from a recent HIV seroconversion have been reported. CASE PRESENTATION:
      In January 2015, a 72-year-old man presented with a rash, fever and diffuse
      myalgias after returning from a fortnight in Cuba. In the context of the current
      polemic, Zika was considered likely. A diagnostic work-up, including dengue fever
      and Zika, was negative. Symptoms resolved spontaneously. In March, the patient
      experienced a sudden loss of vision first on one, a few days later on the other
      eye. Magnetic resonance imaging showed optic nerve enhancement suggesting
      neuritis. Numerous infective causes were sought and the patient was diagnosed
      with HIV. Corticosteroids and antiretroviral therapy were initiated but vision
      did not improve. Four weeks later an optic atrophy developed. After more than a
      year of follow-up the patient remains blind. Stored serum from January revealed a
      detectable viremia with a negative Western blot assay, typical of acute HIV
      infection. CONCLUSIONS: Optic neuritis is a rare complication of early HIV
      infection. Only four others cases have been described, some of which recovered
      their vision after the administration of corticosteroids and/or ARV treatment.
      The balance between ischemic and neuroimmune processes may play a role in
      recovery. Delayed diagnosis, due to an unjustified focus on the Zika virus may
      have contributed to the tragic outcome.

PMID- 29195505
TI  - Type 2 diabetes mellitus is associated with a lower fibrous cap thickness but has
      no impact on calcification morphology: an intracoronary optical coherence
      tomography study.
AB  - BACKGROUND: Patients with type 2 diabetes (T2DM) are at high risk for
      cardiovascular events, which usually arise from the rupture of a vulnerable
      coronary plaque. The minimal fibrous cap thickness (FCT) overlying a necrotic
      lipid core is an established predictor for plaque rupture. Recently, coronary
      calcification has emerged as a relevant feature of plaque vulnerability. However,
      the impact of T2DM on these morphological plaque parameters is largely
      unexplored. Therefore, this study aimed to compare differences of coronary plaque
      morphology in patients with and without T2DM with a particular focus on coronary
      calcification. METHODS: In 91 patients (T2DM = 56, non-T2DM = 35) with 105
      coronary de novo lesions (T2DM = 56, non-T2DM = 49) plaque morphology and
      calcification were analyzed using optical coherence tomography (OCT) prior to
      coronary intervention. RESULTS: Patients with T2DM had a lower minimal FCT (80.4
      +/- 27.0 um vs. 106.8 +/- 27.8 um, p < 0.001) and a higher percent area stenosis
      (77.9 +/- 8.1% vs. 71.7 +/- 11.2%, p = 0.001) compared to non-diabetic subjects.
      However, patients with and without T2DM had a similar total number of
      calcifications (4.0 +/- 2.6 vs. 4.2 +/- 3.1, p = ns) and no significant
      difference was detected in the number of micro- (0.34 +/- 0.79 vs. 0.31 +/-
      0.71), spotty (2.11 +/- 1.77 vs. 2.37 +/- 1.89) or macro-calcifications (1.55 +/-
      1.13 vs. 1.53 +/- 0.71, all p = ns). The mean calcium arc (82.3 +/- 44.8 degrees 
      vs. 73.7 +/- 31.6), the mean thickness of calcification (0.54 +/- 0.13 mm vs.
      0.51 +/- 0.15 mm), the mean calcified area (0.99 +/- 0.72 mm2 vs. 0.78 +/- 0.49
      mm2), the mean depth of calcification (172 +/- 192 MUm vs. 160 +/- 76 MUm) and
      the cap thickness overlying the calcification (50 +/- 71 MUm vs. 62 +/- 61 MUm)
      did not differ between the diabetic and non-diabetic groups (all p = ns).
      CONCLUSION: T2DM has an impact on the minimal FCT of the coronary target lesion,
      but not on localization, size, shape or extent of calcification. Thus, the
      minimal FCT overlying the necrotic lipid core but not calcification is likely to
      contribute to the increased plaque vulnerability observed in patients with T2DM.

PMID- 29195506
TI  - Treatment of meningioma and glioma with protons and carbon ions.
AB  - The rapid rise of particle therapy across the world necessitates evidence to
      justify its ever-increasing utilization. This narrative review summarizes the
      current status of these technologies on treatment of both meningiomas and
      gliomas, the most common benign and malignant primary brain tumors, respectively.
      Proton beam therapy (PBT) for meningiomas displays high rates of long-term local
      control, low rates of symptomatic deterioration, along with the potential for
      safe dose-escalation in select (but not necessarily routine) cases. PBT is also
      associated with low adverse events and maintenance of functional outcomes, which
      have implications for quality of life and cost-effectiveness measures going
      forward. Data on carbon ion radiation therapy (CIRT) are limited; existing series
      describe virtually no high-grade toxicities and high local control. Regarding the
      few available data on low-grade gliomas, PBT provides opportunities to dose
      escalate while affording no increase of severe toxicities, along with maintaining
      appropriate quality of life. Although dose-escalation for low-grade disease has
      been less frequently performed than for glioblastoma, PBT and CIRT continue to be
      utilized for the latter, and also have potential for safer re-irradiation of high
      grade gliomas. For both neoplasms, the impact of superior dosimetric profiles
      with endpoints such as neurocognitive decline and neurologic funcionality, are
      also discussed to the extent of requiring more data to support the utility of
      particle therapy. Caveats to these data are also described, such as the largely
      retrospective nature of the available studies, patient selection, and
      heterogeneity in patient population as well as treatment (including mixed
      photon/particle treatment). Nevertheless, multiple prospective trials (which may
      partially attenuate those concerns) are also discussed. In light of the low
      quantity and quality of available data, major questions remain regarding economic
      concerns as well.

PMID- 29195507
TI  - Expert consensus on re-irradiation for recurrent glioma.
AB  - PURPOSE: To investigate radiation oncologists' opinions on important
      considerations to offering re-irradiation (re-RT) as a treatment option for
      recurrent glioma. MATERIALS AND METHODS: A survey was conducted with 13 radiation
      oncologists involved in the care of central nervous system tumor patients. The
      survey was comprised of 49 questions divided into 2 domains: a demographic
      section (10 questions) and a case section (5 re-RT cases with 5 to 6 questions
      representing one or several re-RT treatment dilemmas as may be encountered in the
      clinic). Respondents were asked to rate the relevance of various factors to
      offering re-RT, respond to the cases with a decision to offer re-RT vs. not,
      volume to be treated, margins to be employed, dose/fractionation suggested and
      any additional comments with respect to rationale in each scenario. RESULTS:
      Sixty nine percent of responders have been practicing for greater than 10 years
      and 61% have re-RT 20 to 100 patients to date, with 54% seeing 2-5 re-RT cases
      per month and retreating 1-2 patients per month. Recurrent tumor volume, time
      since previous radiation therapy, previously administered dose to organs at risk
      and patient performance status were rated by the majority of responders (85%,
      92%, 77%, and 69% respectively) as extremely relevant or very relevant to
      offering re-RT as an option. CONCLUSION: The experts' practice of re-RT is still
      heterogeneous, reflecting the paucity of high-quality prospective data available
      for decision-making. Nevertheless, practicing radiation oncologists can support
      own decisions by referring to the cases found suitable for re-RT in this survey.

PMID- 29195508
TI  - THBD sequence variants potentially related to recurrent pregnancy loss.
AB  - Recurrent pregnancy loss (RPL) is a frequently occurring disease, which is
      classified as idiopathic in more than 50% of cases. THBD, the endothelial cell
      receptor for thrombin, has been associated with distinct biological processes and
      considered a coherent RPL-related candidate gene. In the present study, we have
      sequenced the complete coding region of THBD in 262 patients affected by RPL.
      Bioinformatics analysis and screening of controls strongly suggested that the
      THBD-p.Trp153Gly mutation might be related to RPL aetiology. It could be used,
      after its validation by functional assays, as a molecular marker for
      diagnostic/prognostic purposes.

PMID- 29195509
TI  - DPP-4 inhibition with linagliptin ameliorates the progression of premature aging
      in klotho-/- mice.
AB  - BACKGROUND: The potential of anti-aging effect of DPP-4 inhibitors is unknown.
      This study was performed to determine whether linagliptin, a DPP-4 inhibitor,
      could protect against premature aging in klotho-/- mice. METHODS: Klotho-/- mice
      exhibit multiple phenotypes resembling human premature aging, including extremely
      shortened life span, cognitive impairment, hippocampal neurodegeneration, hair
      loss, muscle atrophy, hypoglycemia, etc. To investigate the effect of linagliptin
      on these aging-related phenotypes, male klotho-/- mice were divided into two
      groups: (1) control group fed the standard diet, and (2) linagliptin group fed
      the standard diet containing linagliptin. Treatment with linagliptin was
      performed for 4 weeks. The effect of linagliptin on the above mentioned aging
      related phenotypes was examined. RESULTS: Body weight of klotho-/- mice was
      greater in linagliptin group than in control group (11.1 +/- 0.3 vs 9.9 +/- 0.3
      g; P < 0.01), which was associated with greater gastrocnemius muscle weight (P <
      0.01) and greater kidney weight (P < 0.05) in linagliptin group. Thus,
      linagliptin significantly prevented body weight loss in klotho-/- mice. Survival
      rate of klotho-/- mice was greater in linagliptin group (93%) compared to control
      group (67%), although the difference did not reach statistical significance (P =
      0.08). None of linagliptin-treated klotho-/- mice had alopecia during the
      treatment (P < 0.05 vs control klotho-/- mice). Latency of klotho-/- mice in
      passive avoidance test was larger in linagliptin group than in control group (P <
      0.05), indicating the amelioration of cognitive impairment by linagliptin.
      Cerebral blood flow of klotho-/- mice was larger in linagliptin group than in
      control group (P < 0.01), being associated with greater cerebral phospho-eNOS
      levels (P < 0.05) in linagliptin group. Neuronal cell number in hippocampal CA1
      region was greater in linagliptin group than in control group (P < 0.05).
      Linagliptin group had greater cerebral phospho-Akt (P < 0.05) and phospho-CREB (P
      < 0.05) than control group. Thus, linagliptin ameliorated brain aging in klotho-/
      mice. The degree of hypoglycemia in klotho-/- mice was less in linagliptin group
      than in control group, as estimated by the findings of OGTT. CONCLUSIONS: Out
      work provided the evidence that DPP-4 inhibition with linagliptin slowed the
      progression of premature aging in klotho-/- mice, and provided a novel insight
      into the potential role of DPP-4 in the mechanism of premature aging.

PMID- 29195511
TI  - Orthodontic management by functional activator treatment: a case report.
AB  - BACKGROUND: Managing orthodontic treatment is often very difficult for the
      orthodontist. Many devices are used during the orthopedic phase of orthodontic
      treatment, always with different functions. We describe a case of orthodontic
      management treated with the Equilibrator O.S.A. device (equilibrator designed by
      Ovidi, Santi, and Aprile for Eptamed SRL; Cesena, Italy; www.eptamed.com ). CASE
      PRESENTATION: A healthy 10-year-old white boy presented with a skeletal class II,
      division 1 malocclusion, molar class II, exhibiting an overjet of 7 mm prior to
      treatment. For treatment, we only used the Equilibrator O.S.A. device.
      CONCLUSIONS: We successfully treated an orthopedic/orthodontic case with a
      particular device that we describe here.

PMID- 29195510
TI  - Cerebrovascular pathology in Down syndrome and Alzheimer disease.
AB  - People with Down syndrome (DS) are at high risk for developing Alzheimer disease
      (AD) with age. Typically, by age 40 years, most people with DS have sufficient
      neuropathology for an AD diagnosis. Interestingly, atherosclerosis and
      hypertension are atypical in DS with age, suggesting the lack of these vascular
      risk factors may be associated with reduced cerebrovascular pathology. However,
      because the extra copy of APP leads to increased beta-amyloid peptide (Abeta)
      accumulation in DS, we hypothesized that there would be more extensive and
      widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic
      AD. To test this hypothesis CAA, atherosclerosis and arteriolosclerosis were used
      as measures of cerebrovascular pathology and compared in post mortem tissue from
      individuals with DS (n = 32), sporadic AD (n = 80) and controls (n = 37). CAA was
      observed with significantly higher frequencies in brains of individuals with DS
      compared to sporadic AD and controls. Atherosclerosis and arteriolosclerosis were
      rare in the cases with DS. CAA in DS may be a target for future interventional
      clinical trials.

PMID- 29195513
TI  - Factors Related to Co-Offending and Coerced Offending Among Female Sex Offenders:
      The Role of Childhood and Adult Trauma Histories.
AB  - Research suggests two important domains of women's sexual offending: co
      offending, in which additional perpetrators are present with the woman during the
      crime, and coerced offending, in which the woman feels pressured by someone else
      to commit the crime. This exploratory analysis examines these 2 domains using
      self-report data from 60 incarcerated female sex offenders (FSOs) in a Midwestern
      state. In addition to indicating whether a co-offender was present and whether
      they felt pressure to commit the sex offense for which they were incarcerated,
      participants provided demographic information about themselves, the victim, and
      the offense, as well as about their own trauma, substance abuse, and mental
      illness histories. Results indicate that childhood and adult trauma histories are
      related to both co-offending and coerced offending among FSOs. Implications for
      theory, policy and practice, and future research are discussed.

PMID- 29195514
TI  - College Students' Perspectives on Campus Health Centers as a Sexual Assault
      Resource: A Qualitative Analysis.
AB  - Students' perspectives of student health centers as a resource for sexual
      violence were examined. A qualitative, descriptive research design was used. Data
      were collected from 37 female undergraduate students in March 2016. Four focus
      groups were conducted and analyzed using thematic analysis techniques. Three
      themes emerged: (a) supports and barriers to using student health centers for
      sexual violence; (b) student health centers' responsibility to educate students
      about sexual violence; and (c) student health centers' responsibility to use
      campus-wide, comprehensive sexual violence efforts. Participants provided several
      recommendations to assist student health centers with addressing sexual violence.
      To maximize utility as an on-campus sexual violence resource, student health
      centers should foster a climate that is supportive of students' use of the
      facility and tailor their efforts to address students' needs. Student health
      center recommendations and suggestions for future research are provided.

PMID- 29195512
TI  - Blood-brain barrier hyperpermeability precedes demyelination in the cuprizone
      model.
AB  - In neuroinflammatory disorders such as multiple sclerosis, the physiological
      function of the blood-brain barrier (BBB) is perturbed, particularly in
      demyelinating lesions and supposedly secondary to acute demyelinating pathology.
      Using the toxic non-inflammatory cuprizone model of demyelination, we
      demonstrate, however, that the onset of persistent BBB impairment precedes
      demyelination. In addition to a direct effect of cuprizone on endothelial cells,
      a plethora of inflammatory mediators, which are mainly of astroglial origin
      during the initial disease phase, likely contribute to the destabilization of
      endothelial barrier function in vivo. Our study reveals that, at different time
      points of pathology and in different CNS regions, the level of gliosis correlates
      with the extent of BBB hyperpermeability and edema. Furthermore, in mutant mice
      with abolished type 3 CXC chemokine receptor (CXCR3) signaling, inflammatory
      responses are dampened and BBB dysfunction ameliorated. Together, these data have
      implications for understanding the role of BBB permeability in the pathogenesis
      of demyelinating disease.

PMID- 29195515
TI  - The Role of Objectification in the Victimization and Perpetration of Intimate
      Partner Violence.
AB  - Intimate partner violence (IPV) is a substantial health concern and identifying
      risk factors for IPV is a research priority. We examined the relationship between
      severe IPV and objectification of the self and other sex across participant sex.
      A sample of 1,005 male and female university students completed a series of
      online questionnaires that measure levels of self-objectification,
      objectification of the other sex, and histories of severe IPV victimization and
      perpetration. Self-objectification was associated with severe psychological
      aggression, physical assault, and sexual coercion victimization in females, but
      not in males. Objectification of the other sex was associated with severe
      psychological aggression and physical assault perpetration in males, but not in
      females. These findings contribute to our understanding of gender similarities
      and differences in IPV.

PMID- 29195516
TI  - Economic Abuse Within Intimate Partner Violence: A Review of the Literature.
AB  - This article reviews the literature on the measurement of, impact of, and
      interventions for economic abuse within intimate partner relationships. Current
      assessment measures for economic abuse, along with estimates of the prevalence of
      economic abuse, are reviewed and critiqued. Research exploring the impact of
      economic abuse on the victim's mental health and psychological well-being, family
      formations and parenting practices, and children's behaviors and youth outcomes
      are presented. Recently developed interventions, including financial literacy
      program models, are discussed and emphasized as a critical service to increase
      victims' economic self-efficacy, financial literacy, and financial behaviors.
      Finally, the review provides detailed recommendations on incorporating economic
      abuse as a central component of domestic violence research, practice, and
      policies.

PMID- 29195517
TI  - Organized Activity Participation and Relational Aggression: The Role of Positive
      Youth Development.
AB  - Relational aggression among early adolescents is a pervasive problem that
      negatively influences the health and well-being of youth. Strength-based
      approaches such as positive youth development (PYD) are a promising way to reduce
      risk of detrimental outcomes such as relational aggression. Participation in
      organized activities is a key way that youth build assets related to PYD. Yet,
      few researchers have examined empirically assets related to PYD as a mechanism by
      which organized activity participation may help reduce risk of relational
      aggression. In this study, we used structural equation modeling to investigate if
      assets associated with PYD mediate the relationship between organized activity
      participation and relational aggression using survey data from a diverse, school
      based sample of early adolescents (N = 196; mean age = 12.39 years; SD = 0.52;
      60% female; 45% African American, 27% White, 21% multiracial, and 7% other, 71%
      economically disadvantaged). We tested 2 competing models, 1 with decomposed PYD
      factors and 1 with an integrated PYD factor. Our results suggest that PYD better
      fit as an integrated versus decomposed construct, providing support for the
      notion that youth benefit most from assets related to PYD when they operate
      collectively. Our results also provide support for PYD-related factors as a
      mechanism by which participation may reduce risk of relational aggression.
      Limitations of this study, and implications for prevention are discussed.

PMID- 29195518
TI  - Characteristics of Intimate Partner Violence Victimization Experienced by a
      Sample of Portuguese Men.
AB  - International research has established that men can be victims of intimate
      partner violence (IPV). In Portugal, this phenomenon has not yet received
      scientific or social attention, although since the 1990s, IPV has been
      acknowledged as a notable problem. An online cross-sectional study was conducted
      with 89 heterosexual men who, after completing the Revised Conflict Tactics
      Scales, identified themselves as victims of IPV. We examined the prevalence of
      IPV, its context, its perceived impact, men's reactions after an episode of
      violence, men's perceived motives for the partner's aggressive behavior, and
      reasons that prevented men from leaving the abusive relationship. The results
      revealed many similarities to the findings in the literature on female victims
      and are discussed in terms of their practical implications. Increased knowledge
      of this underreported phenomenon is vital to the development of suitable policies
      and support services.

PMID- 29195519
TI  - Reducing Violence in Correctional Institutions: Revalidation of the Inmate Risk
      Assessment for Violent, Nonsexual Victimization.
AB  - Jail and prison administrators are responsible for ensuring institutional safety
      and order. Recent estimates indicate violence in correctional institutions is
      pervasive. One promising approach to reduce institutional violence is using a
      risk assessment to predict the likelihood of victimization. Once corrections
      officials identify high victimization risk offenders, these authorities can take
      steps to triage interventions to mitigate such risks. This strategy, however,
      requires a classification instrument that is available and predictively valid. In
      2014, Labrecque, Smith, and Wooldredge created one such tool-the Inmate Risk
      Assessment for Violent, Nonsexual Victimization (RVNSV). This study reassesses
      the predictive validity of the RVNSV on a sample of adult inmates in the United
      States. The results indicate the RVNSV is a valid predictor of inmate
      victimization, among males and females.

PMID- 29195520
TI  - Police Officers' Rape Myth Acceptance: Examining the Role of Officer
      Characteristics, Estimates of False Reporting, and Social Desirability Bias.
AB  - This study examines police officers' perceptions of sexual assault and those who
      report sexual assault to the police, using a revised version of the Rape Myth
      Acceptance Scale along with a measure of social desirability bias. The study
      includes survey responses from 174 officers from 1 mid-sized police department in
      the Great Lakes region. Results show low to moderate levels of rape myth
      acceptance scores on the Rape Myth Acceptance Scale, with highest scores related
      to victim lying. Officers report very high estimates of false reporting,
      indicating some rape myth acceptance. Officer level of education, rank, and
      estimates of false reporting influence rape myth acceptance; however, social
      desirability bias is an important explanatory factor. Implications for
      measurement and training are discussed.

PMID- 29195521
TI  - Caring Is Social.

PMID- 29195522
TI  - Our Capacity to Care.
AB  - Caring is meaningful work. Unfortunately, the conditions under which health care
      personnel work can reduce caring to an abstract principle that we name rather
      than an everyday practice that we do. Several factors curtail our ability to
      care, including the social construction of caring as feminine and thus less
      worthwhile; the churn of patients through clinics and hospitals; and associated
      responsibilities, such as those that have developed with greater use of
      electronic health records. Work-related stress can activate implicit biases,
      which unconsciously distance personnel from members of stigmatized groups and
      contribute to health care disparities. To improve our capacity to care, we must
      tackle the barriers to caring that exist both within and external to clinics and
      hospitals.

PMID- 29195523
TI  - Painful Reality: Inappropriate Provider Management of Pain as a Determinant of
      Health Care Avoidance.
AB  - Although pain is often characterized as a subjective, highly individualized
      phenomenon, in fact, numerous elements which are simply biological in nature
      underlie interpersonal differences in pain experience that influence the
      effectiveness of provider pain management. Elements acting at the level of
      tissues and cells include signal-transmitting molecules in pain pathways;
      elements acting at the level of the whole person comprise entire brain networks
      and anatomic elements fostering pain vulnerability. However, knowledge of these
      elements and translation of such knowledge into practical means for relieving
      patient pain is dismayingly sparse across the total spectrum of health care
      professionals. A serious consequence of this knowledge and action gap is that
      isolated, or worse yet, repeated, pain experiences may lead to profound mistrust
      of the health care system and its providers and to health care avoidance (e.g.,
      mammography). This article outlines a biologic knowledge base and proposed
      remedies to improve pain management across the entire domain of health care. Key
      components of this approach include enhanced education for providers and
      informational outreach to health care consumers, clarifying pain mechanisms to
      both constituencies. Moreover, increased accountability within the health care
      system is needed, both in knowing and applying well-established biomedical
      knowledge and in best using technical and interpersonal skills necessary for
      effective pain management.

PMID- 29195524
TI  - Race, Racism, and Health Disparities: What Can I Do About It?
AB  - Disparities based on race that target communities of color are consistently
      reported in the management of many diseases. Barriers to health care equity
      include the health care system, the patient, the community, and health care
      providers. This article focuses on the health care system as well as health care
      providers and how racism and our implicit biases affect our medical decision
      making. Health care providers receive little or no training on issues of race and
      racism. As a result, awareness of racism and its impact on health care delivery
      is low. I will discuss a training module that helps improve awareness around
      these issues. Until racial issues are honestly addressed by members of the health
      care team, it is unlikely that we will see significant improvements in racial
      health care disparities for Americans.

PMID- 29195525
TI  - Second Life Patient Scenarios: Enhancing the Diversity of the Nursing Profession.
AB  - Despite the current transformation of the U.S. population to one of increased
      diversity, the majority of nurses employed are from White backgrounds. In
      addition, few secondary school students from ethnically diverse backgrounds or
      from rural regions in the nation are encouraged to pursue a collegiate education
      or to consider nursing as a career. This article describes an innovative 3-year
      program in which one rural university in the southeast used a virtual
      environment, Second Life, to expose secondary students to nursing through role
      playing as avatars interacting with patient case scenarios. Secondary school
      science and health occupations teachers developed patient and environmental
      scenarios under the direction of the nursing program director and the information
      technology director from the university. Throughout the 3 years, 300 rural and
      multicultural students were exposed to virtual world health care learning through
      quizzes with five patient case and environmental scenarios. Student and teacher
      evaluations were positive about their interest in learning obtained through the
      patient case examinations. Technical difficulties during Year 1 were eliminated
      by Year 3. This program demonstrates that use of virtual technologies such as
      Second Life may increase the interest of secondary rural and multicultural
      students in careers in nursing and in pursuing a collegiate education.

PMID- 29195527
TI  - Servant Leadership, Emotional Intelligence: Essential for Baccalaureate Nursing
      Students.
AB  - Baker University Bachelor of Science in Nursing students study servant leadership
      and emotional intelligence in a Leadership and Management in Professional Nursing
      course. The acquisition of these skills increases collaboration with clients and
      colleagues. Servant leadership improves care through encouragement and
      facilitation rather than power (Waterman, 2011). Emotional intelligence allows
      individuals to deal effectively with emotions and is associated with better
      health (Por, Barriball, Fitzpatrick, & Roberts, 2011). Knowledge of servant
      leadership, combined with emotional intelligence, creates a relationship with
      self; encourages relationships with others, clients, and providers; allows
      teamwork participation; and impacts the entire community.

PMID- 29195526
TI  - Use of Simulated Psychosocial Role-Playing to Enhance Nursing Students'
      Development of Soft Skills.
AB  - Effective communication and interaction enable nurses to develop caring,
      empathetic, and respectful relationships with patients and families. However,
      most nurses feel a lack of preparation in the "soft" skills of communication,
      professionalism, and leadership. Nurse managers are seeking graduates with strong
      emotional quotient characteristics such as self-awareness, motivation, self
      regulation, empathy, and social skills. Assisting nursing students to develop
      these intangible, high-level skills presents an ongoing challenge to nurse
      educators. This creative teaching learning strategy examines the use of
      psychosocial role-playing skits to enhance nursing student development of the
      soft skills of nursing. In this strategy, senior level nursing students work in
      small groups to develop and present realistic 3- to 5-minute skits based on
      common nurse-patient, nurse-family, or nurse-health care team interactions that
      incorporate the concepts of therapeutic communication, interpersonal interaction,
      empathy, active listening, teamwork, delegation, and/or professionalism, followed
      by a debriefing session. Student feedback suggests that confidence and competence
      related to the skills of therapeutic communication, interpersonal interaction,
      empathy, active listening, teamwork, delegation, and professionalism may improve
      by incorporating soft skill psychosocial role-playing into a nursing education
      course of study.

PMID- 29195528
TI  - Empowering Nursing Students: Fourteen Golden Rules for Clinical Day.
AB  - Few nursing school experiences are as intimidating as starting a clinical
      rotation. By providing adequate scaffolding, clinical instructors can help
      empower nursing students as they begin to provide care in a variety of clinical
      settings. This article presents the 14 golden rules for clinical day, a unique
      form of scaffolding based on my own experience as a nursing clinical instructor.
      The right scaffolding can help students to overcome the sense of otherness they
      often experience at clinical sites and to blossom into competent, confident
      nurses who put their patients first.

PMID- 29195529
TI  - Building Relationship-Based Care Among Nurses: A Holistic, Exploratory Project.
AB  - In this exploratory project, efforts were made to strengthen a relationship
      centered, caring milieu to improve communication among nursing staff and to help
      nurses identify and constructively resolve conflicts. Eighteen interactive
      workshops addressed communication patterns and helped participants identify
      causes of conflict, facilitate dialogue, improve collaboration, and resolve
      workplace conflict. The experiential workshops were analyzed with pre- and post
      surveys. Participants perceived as individual and team members that it was less
      important to like one's colleagues and more important to be committed to the same
      purpose/goals. Individuals noted the value of respect for each other, regardless
      of title or position. They reported feeling more hopeful regarding work and that
      practicing tactics to address conflicts made it easier to confront others when
      the team goal was clear and shared. They indicated a desire to continue to build
      on conflict resolution, mediation, stress management, and mindfulness skills.

PMID- 29195530
TI  - Desired Destinations of Homeless Women: Realizing Aspirations Within the Context
      of Homelessness.
AB  - Despite recent decreases, homelessness remains a substantial problem in the
      United States. Homelessness is associated with poor health, and homeless women
      experience earlier mortality than their housed counterparts. Understanding the
      aspirations of homeless women may offer service providers avenues for
      intervention to increase well-being among this vulnerable population. This study,
      a secondary analysis of transcribed interviews (n = 20), provides insight into
      the aspirations of homeless women. Opportunities for service providers to
      intervene on these aspirations within the context of homelessness are offered.

PMID- 29195531
TI  - Workplace Violence Against Nurses: Making It Safe to Care.
AB  - This article explores the topic of workplace violence in the health care setting.
      A definition of workplace violence and those who are most vulnerable is provided.
      National and state legislation that addresses the topic of workplace violence
      will be discussed. Other organizations such as the American Nurses Association
      and The Joint Commission and their position statements will be explored. Lastly,
      strategies targeting workplace violence prevention and the barriers to
      implementing identified strategies will be discussed. Workplace violence is a
      rapidly growing concern for those working in health care. This article provides
      recommendations for legislative and workplace actions to protect health care
      workers.

PMID- 29195532
TI  - Article Review.

PMID- 29195533
TI  - Global Determinants: Our Human Interconnectedness.

PMID- 29195534
TI  - Identifying Indicators of Healthy Work Environments in Nursing as Determinants of
      Health in the 21st Century.
AB  - A paradigm shift is occurring in the definition of health and therefore also in
      the determinants of health. Social determinants of health, considered by many to
      be the premises of good health and a purposeful life, are now the focus of
      attention in determinants of health. These determinants of health bring attention
      to the conditions in which people are born and live and work. This article
      proposes that indicators of healthy work environments in nursing can be
      identified as determinants of health. Study findings from around the world
      confirm that the health and well-being of nurses and their patients is related to
      nurses' work and work environments. Therefore, the working lives of nurses should
      be identified as an inseparable part of their personal lives, leading to
      consideration of work environments and thereby the quality of nurse's work lives
      as determinants of health in the 21st century.

PMID- 29195535
TI  - Supporting Health and Well-Being for Resettled Refugee Women: The Global Women's
      Group.
AB  - Women refugees arrive in the United States often having experienced extreme
      levels of poverty, deprivation, and violence, including gender-based violence,
      which can severely affect their physical and psychological health and well-being.
      A women's group was initiated to improve the health and well-being of refugee
      women in Durham, North Carolina, through a collaboratively designed, culturally
      appropriate health literacy intervention for women based on mutually identified
      needs; to empower them to seek preventive health services and screening through
      knowledge and skills about health needs and access to care; and to create an
      environment for the development of a supportive social/peer network for the
      prevention of social isolation and mental health issues related to the refugee
      experience.

PMID- 29195536
TI  - Mountains, Melting Pot, and Microcosm: Health Care Delay and Dengue/Zika
      Interplay on Hawaii Island.
AB  - Human history in the Hawaiian Islands offers a sobering study in the population
      dynamics of infectious disease. The indigenous population numbering an estimated
      half million people prior to Western contact in 1778 was reduced to less than
      24,000 by 1920. Much of the decline occurred in the earliest decades after
      contact with Western diseases including measles, chicken pox, polio,
      tuberculosis, and venereal disease. A recent outbreak on the Island of Hawaii
      (also called the Big Island) of imported dengue fever, an illness endemic in 100
      countries affecting an estimated 100-400 million people worldwide, provides
      insights into the problems and prospects for health care policy in managing
      mosquito-borne disease in a multicultural setting of geographic isolation and
      health care provider shortage. This incident represents in microcosm a practice
      run, applicable in many contexts, for an initial localized appearance of Zika
      virus infection, with important lessons for effective health care management in a
      rapidly moving and fluid arena.

PMID- 29195537
TI  - Nurses See "The Big Picture": Addressing Climate Change as a Social Determinant
      of Global Health.
AB  - Although it is well known that health is influenced by social determinants,
      climate change is an underrepresented determinant of health within nursing and
      health care literature, curriculum, and practice. There is urgent need to
      recognize climate change as a current and future threat to human and
      environmental health. This article describes the role of nursing in taking action
      on climate change now and in the future. The profession of nursing, with its
      ongoing commitment to social justice and its unique position to collaborate with
      patients and other health care professionals, is particularly well situated to
      activate change to protect and promote the health of individuals, populations,
      and future generations.

PMID- 29195538
TI  - Hidden Grief and Lasting Emotions in Emergency Department Nurses.
AB  - The emergency department (ED) environment poses unique risks to developing moral
      distress and posttraumatic stress disorder (PTSD) in nurses. This impacts ED
      registered nurses' (RNs') ability to remain resilient. The purpose of this
      article is to explore the benefit of recognizing the signs and symptoms of
      burnout, introduce interventions to combat PTSD, and improve resiliency in ED
      RNs. The use of the wounded healer theory provides a framework to help nurse
      managers develop strategies such as critical incident stress debriefing (CISD) to
      address emotional distress.

PMID- 29195539
TI  - Barriers to Teaching Social Determinants of Health: Nursing Study-Abroad Programs
      in a Digital Age.
AB  - The social determinants of health are the conditions in which humans are born,
      grow up, live, work, and age (World Health Organization [WHO], 2012). In nursing
      programs, this content is typically taught in community health courses. Another
      strategy for teaching students how to understand the social determinants of
      health is study-abroad courses. Budding nurses can learn how to assess conditions
      that influence the health of a community. Conducting this assessment in a culture
      that differs from the student's own can help highlight what factors impact one's
      own health. For the past eight years, the author has been teaching the social and
      cultural determinants of health to nursing students by taking them on 3-week
      cultural immersion/community health studyabroad programs. Destinations have
      included Ghana, Austria, the Netherlands, and Thailand. This article presents
      observations on how the teaching of social determinants of health has changed
      during the period 2008-2016.

PMID- 29195540
TI  - The Impact of the Primary Nursing Model on Cultural Improvement: A Mixed-Method
      Study.
AB  - Evaluating the implementation of care models such as Primary Nursing requires
      assessment of both short-term and long-term outcomes. In a hospital in Piemonte,
      Italy, a mixedmethod time-series study was conducted to assess if and how the
      organizational culture of nurses changed in relation to the implementation of a
      new organizational model of care. Instruments used included the Condition of Work
      Effectiveness Questionnaire (CWEQ II) and an investigator-developed questionnaire
      to evaluate perceptions of dimensions consistent with Primary Nursing. Results
      showed a significant culture change over time related to the implementation of
      Primary Nursing, mainly in terms of nurses' understanding of their professional
      role specifications. In addition, the results supported a relationship between
      being involved in the project implementation and the procedural and cultural
      approach adopted.

PMID- 29195542
TI  - Communication With Patients and Families as a Global Determinant of Health:
      Lessons From Care of Children With Special Health Care Needs.
AB  - Until recently, patients and families were not considered by all providers to be
      valued members of the health care team. Many providers made decisions away from
      the bedside and then told the patient and family what they could expect from the
      plan of care. This top-down approach is not limited to one country or culture but
      reflects an attitude prevalent in biomedicine around the globe. However, the
      paradigm is beginning to shift. Skyrocketing health care costs have prompted
      value-based purchasing, in which third-party payment is linked to patient
      outcomes and satisfaction. Providers and health care organizations are scrambling
      for evidence-based models to improve communication and other satisfaction-related
      criteria. This article proposes that teaching patients and families use of the
      Situation/Background/Assessment/Recommendations (SBAR) tool, traditionally used
      among health care professionals, will improve communication, enhance patient and
      family satisfaction, and potentially improve patient outcomes overall. The
      SBAR4Patients project demonstrates the positive impact SBAR can have on parents
      of chronically ill children.

PMID- 29195541
TI  - Walking for Heart Health: A Study of Adult Women in Rural New York.
AB  - PURPOSE: The study was undertaken to partially address the number one priority
      for Delaware County for 2013-2017: reducing chronic illness including heart
      disease and obesity (Delaware County Public Health, 2013). Thus, the purpose was
      to examine the effects of a 10-week walking program on outcomes, such as blood
      pressure (BP), total cholesterol (TC), high-density lipoprotein (HDL) levels,
      body mass index (BMI), 10-year cardiovascular risk, and results of a 6-minute
      walk test, for adult women in a rural community in New York. METHODS: A quasi
      experimental study conducted 8 paired t tests of pre- and postdata using
      Bonferroni correction for multiple t tests. A convenience sample of 70 retained
      62 to completion. Pre- and post-BMI, TC, HDL, BP, and a 6-minute walk test data
      were collected for each participant. Pedometer activity was collected throughout
      the program with computer downloads at 5 and 10 weeks. Sociodemographic variables
      including age, self-reported ethnicity, and educational level were used to
      describe the sample and trends in the data. FINDINGS: Age range was 29-79 years
      (M = 55) years. Mean pretest weight was 181 lb; mean BMI was 30.7 kg/m2. There
      was a statistically significant improvement (p < .05) in weight, BMI, TC,
      systolic blood pressure (SBP), and 6-minute walk test. All comparisons retained
      significance except TC after the Bonferroni correction. There was also a
      statistically significant increase (p < .05) in aerobic steps from midway to end
      of study after an incentive raffle challenge was introduced. CONCLUSIONS: The
      data suggest that a community walking program using pedometers with tracking
      capabilities was successful in increasing steps and improving select
      cardiovascular disease (CVD) risk factors in a group of women in a rural
      community in New York.

PMID- 29195543
TI  - Reflections From the Other Side: The Refugee Journey to Health and Well-Being.
AB  - The refugee crisis is an urgent global health issue; the number of displaced
      people has escalated to its worst point in recorded history. To explore the
      refugee phenomenon as a social determinant of health, this article examines the
      experience of Somali refugees in Minnesota. Health care barriers unique to
      refugees are explored through the firstperson perspective of one Somali woman who
      ultimately became a nurse.

PMID- 29195544
TI  - Identifying Health Needs in Peru Through Use of a Community Survey.
AB  - Students and faculty from a Midwestern college conducted a neighborhood community
      needs assessment in an impoverished area of a Peruvian city to identify health
      needs of residents. Students interviewed residents in their homes, asking about
      the need for medical, dental, and ophthalmic care and screening for chronic
      conditions such as diabetes, heart disease, and tuberculosis. The survey provided
      necessary information to medical mission workers and allowed students to directly
      observe family living conditions while assessing psychosocial needs of the
      families interviewed. The challenges of this survey included differing
      expectations, language barriers, recruiting neighborhood volunteers, safety risks
      to students, and mistrust by neighborhood residents.

PMID- 29195545
TI  - The White Book of Skin Cancer of the Spanish Academy of Dermatology and
      Venereology (AEDV).

PMID- 29195546
TI  - HRS is a global society.

PMID- 29195547
TI  - The role of interventricular conduction delay to predict clinical response with
      cardiac resynchronization therapy.
AB  - BACKGROUND: Pacing at sites with late electrical activation or greater
      interventricular delay is associated with improvement in measures of cardiac
      resynchronization therapy (CRT) response, primarily reverse remodeling. However,
      little is known about whether such lead positions improve heart failure (HF)
      clinical outcomes. OBJECTIVE: The purpose of this study was to assess the
      association between interventricular electrical delay and HF clinical outcomes.
      METHODS: The Pacing Evaluation-Atrial SUpport Study was a multicenter randomized
      trial of patients undergoing CRT-defibrillator implantation. Interventricular
      delay was measured as the unpaced right ventricle-left ventricle (RV-LV) interval
      in sinus rhythm. The HF clinical composite score was the primary end point. In
      addition, the time to first HF hospitalization or death was measured and events
      were adjudicated by a blinded core laboratory. The cohort was divided at the
      median RV-LV interval into short (<67 ms) and long (>=67 ms) subgroups. In
      addition, receiver operating characteristic curves were constructed to identify
      the optimal cutoff of the RV-LV interval and spline analysis was performed to
      assess RV-LV interval as a continuous variable. RESULTS: A total of 1342 patients
      were included in this study. The clinical composite score at 1 year differed
      between groups, with more patients improving and fewer patients worsening in the
      long RV-LV group (P = .014). The time to first HF hospitalization or mortality
      also differed with a lower risk of an event in the long RV-LV group (hazard ratio
      0.62; P = .002). Multivariate analysis showed that RV-LV time (hazard ratio 0.71;
      P = .038) and sex were independent predictors of this outcome. CONCLUSION:
      Baseline interventricular delay is a strong independent predictor of clinical
      response to CRT.

PMID- 29195548
TI  - When and how to target atrial fibrillation sources outside the pulmonary veins: A
      practical approach.

PMID- 29195549
TI  - A supraventricular tachycardia with atrioventricular block in a patient with a
      previous anteroseptal myocardial infarction.

PMID- 29195550
TI  - A three-time-point method for assessing kinetic parameters of 64Cu-labeled
      Ramucirumab trapping in VEGFR-2 positive lung tumors.
AB  - OBJECTIVE: To describe a three-time-point method for estimating kinetic
      parameters involved in 64Cu-labeled Ramucirumab (64Cu-NOTA-RamAb) trapping of
      VEGFR-2 positive lung tumors. MATERIALS AND METHODS: Positron emission tomography
      (microPET) data of tumor-bearing mice for 64Cu-NOTA-RamAb trapping in VEGFR-2
      positive HCC4006 tumor were used, involving tissue activity measurements acquired
      at 3, 24 and 48 h post-injection, without and with administration of RamAb
      blocking dose. A kinetic model provided an analytical formula describing the
      tissue time-activity-curve, involving 64Cu-NOTA-RamAb uptake (Ki), release rate
      constant (kR) and fraction of free tracer in blood and interstitial volume (F).
      RESULTS: Fitting analytical formula outcomes on mean microPET data yielded values
      of the kinetic parameters: Ki = 0.0314/0.0123 gram of blood per hour per gram of
      tissue, kR = 0.0387/0.0313 h-1 and F = 0.2075/0.2007 gram of blood per gram of
      tissue, without/with RamAb blocking dose, respectively (R = 0.99999 for the graph
      displaying microPET versus theoretical data; P < .01). CONCLUSIONS: Three
      independent kinetic parameters (Ki, kR and F) can be assessed from three data
      points acquired at early, mid and late imaging, i.e., at 3, 24 and 48 h post
      injection, for further characterization of 64Cu-NOTA-RamAb trapping in VEGFR-2
      positive lung tumors.

PMID- 29195551
TI  - Effectiveness of a simple and real-time baseline shift monitoring system during
      stereotactic body radiation therapy of lung tumors.
AB  - PURPOSE: This study aimed to clinically validate a simple real-time baseline
      shift monitoring system in a prospective study of consecutive patients undergoing
      stereotactic body radiation therapy (SBRT) of lung tumors, and to investigate
      baseline shift due to intrafraction motion of the patient's body during lung
      SBRT. METHODS: Ten consecutive patients with peripheral lung tumors were treated
      by SBRT consisting of four fractions of 12 Gy each, with a total dose of 48 Gy.
      During treatment, each patient's geometric displacement in the anterior-posterior
      and left-right directions (the baseline shift) was measured using a real-time
      monitoring webcam system. Displacement between the start and end of treatment was
      measured using an X-ray fluoroscopic imaging system. The displacement
      measurements of the two systems were compared, and the measurements of baseline
      shift acquired by the monitoring system during treatment were analyzed for all
      patients. RESULTS: There was no significant deviation between the monitoring
      system and the X-ray imaging system, with the accuracy of measurement being
      within 1 mm. Measurements using the monitoring system showed that 7 min of
      treatment generated displacements of more than 1 mm in 50% of the patients.
      CONCLUSIONS: Baseline shift of a patient's body may be measured accurately in
      real time, using a monitoring system without X-ray exposure. The manubrium of the
      sternum is a good location for measuring the baseline shift of a patient's body
      at all times. The real-time monitoring system may be useful for measuring the
      baseline shift of a patient's body independently of a gating system.

PMID- 29195552
TI  - Geometric and dosimetric quality assurance using logfiles and a 3D helical diode
      detector for Dynamic WaveArc.
AB  - PURPOSE: To conduct patient-specific geometric and dosimetric quality assurance
      (QA) for the Dynamic WaveArc (DWA) using logfiles and ArcCHECK (Sun Nuclear Inc.,
      Melbourne, FL, USA). METHODS: Twenty DWA plans, 10 for pituitary adenoma and 10
      for prostate cancer, were created using RayStation version 4.7 (RaySearch
      Laboratories, Stockholm, Sweden). Root mean square errors (RMSEs) between the
      actual and planned values in the logfiles were evaluated. Next, the dose
      distributions were reconstructed based on the logfiles. The differences between
      dose-volumetric parameters in the reconstructed plans and those in the original
      plans were calculated. Finally, dose distributions were assessed using ArcCHECK.
      In addition, the reconstructed dose distributions were compared with planned
      ones. RESULTS: The means of RMSEs for the gantry, O-ring, MLC position, and MU
      for all plans were 0.2 degrees , 0.1 degrees , 0.1 mm, and 0.4 MU, respectively.
      Absolute means of the change in PTV D99% were 0.4 +/- 0.4% and 0.1 +/- 0.1%
      points between the original and reconstructed plans for pituitary adenoma and
      prostate cancer, respectively. The mean of the gamma passing rate (3%/3 mm)
      between the measured and planned dose distributions was 97.7%. In addition, that
      between the reconstructed and planned dose distributions was 99.6%. CONCLUSIONS:
      We have demonstrated that the geometric accuracy and gamma passing rates were
      within AAPM 119 and 142 criteria during DWA. Dose differences in the dose
      volumetric parameters using the logfile-based dose reconstruction method were
      also clinically acceptable in DWA.

PMID- 29195553
TI  - Impact of a monolithic silicon detector operating in transmission mode on
      clinical photon beams.
AB  - PURPOSE: To investigate the effect on surface dose, as a function of different
      field sizes and distances from the solid water phantom to transmission detector
      (Dsd), of using the monolithic silicon detector MP512T in transmission mode.
      METHODS: The influence of operating the MP512T in transmission mode on the
      surface dose of a phantom for SSD 100cm was evaluated by using a Markus IC. The
      MP512T was fixed to an adjustable stand holder and was positioned at different
      Dsd, ranging from 0.3 to 24 cm. For each Dsd, measurements were carried out for
      irradiation field sizes of 5 * 5cm2, 8 * 8 cm2 and 10 * 10 cm2. Measurements were
      obtained under two different operational setups, (i) with the MP512T face-up and
      (ii) with the MP512T face-down. In addition, the transmission factors for the
      MP512T and the printed circuit board were only evaluated using a Farmer IC.
      RESULTS: For all Dsd and all field sizes, the MP512T led to the surface dose
      increasing by less than 25% when in the beam. For Dsd >18 cm the surface dose
      increase is less than 5%, and negligible for field size 5 * 5 cm2. The difference
      in the surface dose perturbation for the MP512T operating face up or operating
      face down is negligible (<2%) for all field sizes. The transmission factor of the
      MP512T ranged from 1.020 to 0.9950 for all measured Dsd and field sizes.
      CONCLUSION: The study demonstrated that positioning the MP512T in air between the
      Linac head and the phantom produced negligible perturbation of the surface dose
      for Dsd >18 cm, and was completely transparent for 6 MV photon beams.

PMID- 29195554
TI  - Numerical insight into the Dual Radiation Action Theory.
AB  - This work studies the first and second order mechanisms for the induction of
      lethal lesions in DNA after irradiation with protons and alpha-particles. The
      purpose is to numerically study the mechanisms behind the Dual Radiation Action
      Theory (DRAT) for these heavy particles. A genetic material geometrical model
      with atomic resolution is used. It accounts for the explicit position of 5.47 *
      109 base pairs, organized up to the chromatin level. The GEANT4-DNA Monte Carlo
      code was employed to simulate the interaction of these ions with the genetic
      material model. The number of lethal lesions induced by one- and two-track
      mechanisms was determined as a function of dose. Values of the alpha/beta ratio
      were estimated as well as corresponding relative biological effectiveness (RBE).
      The number of lethal lesions produced by one-track and two-track mechanisms
      depends on the dose and squared dose, respectively, as predicted by the DRAT. RBE
      values consistent with experimental results were found, at least for LET below
      ~100 keV/MUm. Double strand break spatial distributions are qualitatively
      analyzed. According to this work, the alpha parameter determined from cellular
      surviving curves depends on both the physical alpha and beta parameters
      introduced here, and on the specific energy deposited by a single track into the
      region of interest. We found an increment of the beta parameter with LET, yet at
      a slower rate than alpha so that the alpha/beta ratio increases with LET. In
      addition, we observed and explained the saturation of the alpha parameter as the
      dose increases above ~6 Gy.

PMID- 29195555
TI  - Feasibility of beta-particle radioguided surgery for a variety of "nuclear
      medicine" radionuclides.
AB  - PURPOSE: Beta-particle radioguided tumor resection may potentially overcome the
      limitations of conventional gamma-ray guided surgery by eliminating, or at least
      minimizing, the confounding effect of counts contributed by activity in adjacent
      normal tissues. The current study evaluates the clinical feasibility of this
      approach for a variety of radionuclides. Nowadays, the only beta- radioisotope
      suited to radioguided surgery is 90Y. Here, we study the beta- probe prototype
      capability to different radionuclides chosen among those used in nuclear
      medicine. METHODS: The counting efficiency of our probe prototype was evaluated
      for sources of electrons and photons of different energies. Such measurements
      were used to benchmark the Monte Carlo (MC) simulation of the probe behavior,
      especially the parameters related to the simulation of the optical photon
      propagation in the scintillation crystal. Then, the MC simulation was used to
      derive the signal and the background we would measure from a small tumor embedded
      in the patient body if one of the selected radionuclides is used. RESULTS: Based
      on the criterion of detectability of a 0.1 ml tumor for a counting interval of 1
      s and an administered activity of 3 MBq/kg, the current probe yields a detectable
      signal over a wide range of Standard Uptake Values (SUVs) and tumor-to-non-tumor
      activity-concentration ratios (TNRs) for 31Si, 32P, 97Zr, and 188Re. Although
      efficient counting of 83Br, 133I, and 153Sm proved somewhat more problematic, the
      foregoing criterion can be satisfied for these isotopes as well for sufficiently
      high SUVs and TNRs.

PMID- 29195556
TI  - Immobilization for carbon ion beam ablation of cardiac structures in a porcine
      model.
AB  - INTRODUCTION: Whereas hadron therapy of static targets is clinically established,
      treatment of moving organs remains a challenge. One strategy is to minimize
      motion of surrounding tissue mechanically and to mitigate residual motion with an
      appropriate irradiation technique. In this technical note, we present and
      characterize such an immobilization technique for a novel noncancerous
      application: the irradiation of small targets in hearts with scanned carbon ion
      beams in a porcine model for elimination of arrhythmias. MATERIAL AND METHODS: A
      device for immobilization was custom-built. Both for the treatment planning 4D-CT
      scan and for irradiation, breath-hold at end-exhale was enforced using a remotely
      controlled respirator. Target motion was thus reduced to heartbeat only.
      Positioning was verified by orthogonal X-rays followed by couch shift if
      necessary. Reproducibility of bony anatomy, diaphragm, and heart position after
      repositioning and between repeated breath-hold maneuvers was evaluated on X-rays
      and cardiac-gated 4D-CTs. Treatment was post hoc simulated on sequential 4D-CTs
      for a subset of animals, after immediate repositioning and after a delay of one
      week, similar to the delay between imaging and irradiation. RESULTS: Breath-hold
      without repositioning was highly reproducible with an RMS deviation of at most
      one millimeter. 4D-CTs showed larger deformations in soft tissue, but treatment
      simulation on sequential images resulted in full target coverage (V95 >95%).
      CONCLUSION: The method of immobilization permitted reproducible positioning of
      mobile, thoracic targets for range-sensitive particle therapy. The presented
      immobilization strategy could be a reasonable approach for future animal
      investigations with the ultimate goal of translation to therapy in men.

PMID- 29195557
TI  - Eye lens radiation exposure of the medical staff performing interventional
      urology procedures with an over-couch X-ray tube.
AB  - The purpose of this work was to estimate the eye lens radiation exposure of the
      medical staff during interventional urology procedures. The measurements were
      carried out for six medical staff members performing 33 fluoroscopically-guided
      procedures. All procedures were performed with the X-ray tube positioned over the
      couch. The dose equivalents (Hp(0.07)) were measured at the eye level using
      optically stimulated luminescent (OSL) dosimeters and at the chest level with OSL
      dosimeters placed over the protective apron. The ratio of the dose measured close
      to the eye lens and on the chest was determined. The annual eye lens dose was
      estimated based on the workload in the service. For the physician and the
      instrumentalist nurse, the eye to chest dose ratios were 0.9+/-0.4 and 2.6+/-1.6
      (k = 2), respectively. The average doses per procedure received by the eye lens
      were 78+/-24 MUSv and 38+/-18 MUSv, respectively. The eye lens dose per DAP was
      8.4+/-17.5 MUSv/(Gy.cm2) for the physician and 4.1+/-8.7 MUSv/(Gy.cm2) for the
      instrumentalist nurse. The results indicate that the eye lens to chest dose ratio
      greatly varies according to the staff function and that the dose equivalent
      measured by the personal dosimeter worn on the chest may underestimate the eye
      lens dose of some medical staff members.

PMID- 29195558
TI  - Comprehensive clinical commissioning and validation of the RayStation treatment
      planning system for proton therapy with active scanning and passive treatment
      techniques.
AB  - PURPOSE: To commission the treatment planning system (TPS) RayStation for proton
      therapy including beam models for spot scanning and for uniform scanning.
      METHODS: Tests consist of procedures from ESTRO booklet number 7, the German DIN
      for constancy checks of TPSs, and extra tests checking the dose perturbation
      function. The dose distributions within patients were verified in silico by a
      comparison of 65 clinical treatment plans with the TPS XiO. Dose-volume
      parameters, dose differences, and three-dimensional gamma-indices serve as
      measures of similarity. The monthly constancy checks of Raystation have been
      automatized with a script. RESULTS: The basic functionality of the software
      complies with ESTRO booklet number 7. For a few features minor enhancements are
      suggested. The dose distribution in RayStation agrees with the calculation in
      XiO. This is supported by a gamma-index (3mm/3%) pass rate of >98.9% (median over
      59 plans) for the volume within the 20% isodose line and a difference of <0.3% of
      V95 of the PTV (median over 59 plans). If spot scanning is used together with a
      range shifter, the dose level calculated by RayStation can be off by a few
      percent. CONCLUSIONS: RayStation can be used for the creation of clinical proton
      treatment plans. Compared to XiO RayStation has an improved modelling of the
      lateral dose fall-off in passively delivered fields. For spot scanning fields
      with range shifter blocks an empirical adjustment of monitor units is required.
      The computation of perturbed doses also allows the evaluation of the robustness
      of a treatment plan.

PMID- 29195559
TI  - Phase-contrast imaging for body composition measurement.
AB  - PURPOSE: In this paper, we propose a novel method for human body composition
      measurement, especially for the bone mineral density (BMD) measurement. The
      proposed method, using the absorption and differential phase information
      retrieved from X-ray grating-based interferometer (XGBI) to measure the BMD, has
      potential to replace dual-energy X-ray absorptiometry (DEXA), which is currently
      widely used for body composition measurement. METHODS: The DEXA method employs
      two absorption images acquired at two different X-ray spectra (high energy and
      low energy) to calculate the human body composition. In this paper, a new method
      to calculate BMD using a single X-ray measurement is proposed. XGBI is a
      relatively new X-ray technique that provides absorption, phase and scattering
      information simultaneously using a single X-ray spectrum. With the absorption and
      differential phase information retrieved from XGBI, BMD can be measured using
      only one single X-ray spectrum. Numerical simulations are performed with a body
      phantom of bone (Cortical, ICRU-44) surrounded by soft tissue (Soft, ICRU-44).
      BMD is calculated with both the DEXA method and the proposed method. RESULTS:
      Results show that BMD can be measured accurately with the proposed method;
      moreover, better signal-to-noise ratio (SNR) is obtained compared to DEXA.
      CONCLUSION: With the proposed method, BMD can be measured with XGBI setup.
      Further, the proposed method can be realized using current X-ray phase-contrast
      imaging (XPCI) apparatus without any hardware modification, suggesting that this
      technique can be a promising supplementary function to current XPCI equipment.

PMID- 29195560
TI  - gammaTools: A modular multifunction phantom for quality assurance in GammaKnife
      treatments.
AB  - PURPOSE: We present the gammaTools, a new phantom designed to assess geometric
      and dosimetric accuracy in Gamma Knife treatments, together with first tests and
      results of applications. METHODS: The phantom is composed of two modules: the
      imaging module, a regular grid of 1660 control points to evaluate image
      distortions and image registration result and the dosimetry module for delivered
      dose distribution measurements. The phantom is accompanied by a MatLab routine
      for image distortions quantification. Dose measurement are performed with
      Gafchromic films fixed between two inserts and placed in various positions and
      orientations inside the dosimetry module thus covering a volume comparable to the
      full volume of a head. RESULTS: Tests performed to assess the accuracy and
      precision of the imaging module demonstrated sub-millimetric values. As an
      example of possible applications, the phantom was employed to measure image
      distortions of two MRI scanners and to perform dosimetric studies of single shots
      delivered to homogeneous and heterogeneous materials. Due to the phantom
      material, the measured absolute dose do not correspond to the planned dose; doses
      comparisons are thus carried out between normalized dose distributions. Finally,
      an end-to-end test was carried out in the treatment of a neuroma-like target
      which resulted in a 100% gamma passing rate (2% local, 2 mm) and a distance
      between the real target perimeter and the prescription isodose centroids of about
      1 mm. CONCLUSIONS: The tests demonstrate that the proposed phantom is suitable to
      assess both the geometrical and relative dosimetric accuracy of Gamma Knife
      radiosurgery treatments.

PMID- 29195561
TI  - Dose accumulation of multiple high dose rate prostate brachytherapy treatments in
      two commercially available image registration systems.
AB  - PURPOSE: The purpose of this study was to assess whether deformable image
      registration (DIR) is required for dose accumulation of multiple high dose rate
      prostate brachytherapy (HDRPBT) plans treated with the same catheter pattern on
      two different CT datasets. METHOD: DIR was applied to 20 HDRPBT patients'
      planning CT images who received two treatment fractions on sequential days, on
      two different CT datasets, with the same implant. Quality of DIR in Velocity and
      MIM image registration systems was assessed by calculating the Dice Similarity
      Coefficient (DSC) and mean distance to agreement (MDA) for the prostate, urethra
      and rectum contours. Accumulated doses from each system were then calculated
      using the same DIR technique and dose volume histogram (DVH) parameters compared
      to manual addition with no DIR. RESULTS: The average DSC was found to be 0.83
      (Velocity) and 0.84 (MIM), 0.80 (Velocity) and 0.80 (MIM), 0.80 (Velocity) and
      0.81 (MIM), for the prostate, rectum and urethra contours, respectively. The
      average difference in calculated DVH parameters between the two systems using
      dose accumulation was less than 1%, and there was no statistically significant
      difference found between deformably accumulated doses in the two systems versus
      manual DVH addition with no DIR. CONCLUSION: Contour propagation using DIR in
      velocity and MIM was shown to be at least equivalent to inter-observer contouring
      variability on CT. The results also indicate that dose accumulation through
      manual addition of DVH parameters may be sufficient for HDRPBT treatments treated
      with the same catheter pattern on two different CT datasets.

PMID- 29195562
TI  - Abdominal imaging dose in radiology and radiotherapy - Phantom point dose
      measurements, effective dose and secondary cancer risk.
AB  - PURPOSE: To compare abdominal imaging dose from 3D imaging in radiology
      (standard/low-dose/dual-energy CT) and radiotherapy (planning CT, kV cone-beam CT
      (CBCT)). METHODS: Dose was measured by thermoluminescent dosimeters (TLD's)
      placed at 86 positions in an anthropomorphic phantom. Point, organ and effective
      dose were assessed, and secondary cancer risk from imaging was estimated.
      RESULTS: Overall dose and mean organ dose comparisons yield significantly lower
      dose for the optimized radiology protocols (dual-source and care kV), with an
      average dose of 0.34+/-0.01 mGy and 0.54+/-0.01 mGy (average +/- standard
      deviation), respectively. Standard abdominal CT and planning CT involve
      considerably higher dose (13.58 +/- 0.18 mGy and 18.78+/-0.27 mGy, respectively).
      The CBCT dose show a dose fall-off near the field edges. On average, dose is
      reduced as compared with the planning or standard CT (3.79 +/- 0.21 mGy for 220
      degrees  rotation and 7.76 +/- 0.37 mGy for 360 degrees ), unless the high
      quality setting is chosen (20.30 +/- 0.96 mGy). The mean organ doses show a
      similar behavior, which translates to the estimated secondary cancer risk. The
      modelled risk is in the range between 0.4 cases per million patient years (PY)
      for the radiological scans dual-energy and care kV, and 300 cases per million PY
      for the high-quality CBCT setting. CONCLUSIONS: Modern radiotherapy imaging
      techniques (while much lower in dose than radiotherapy), involve considerably
      more dose to the patient than modern radiology techniques. Given the frequency of
      radiotherapy imaging, a further reduction in radiotherapy imaging dose appears to
      be both desirable and technically feasible.

PMID- 29195563
TI  - Awareness of medical radiation exposure among patients: A patient survey as a
      first step for effective communication of ionizing radiation risks.
AB  - INTRODUCTION: The European Directive 2013/59/EURATOM requires patient radiation
      dose information to be included in the medical report of radiological procedures.
      To provide effective communication to the patient, it is necessary to first
      assess the patient's level of knowledge regarding medical exposure. The goal of
      this work is to survey patients' current knowledge level of both medical exposure
      to ionizing radiation and professional disciplines and communication means used
      by patients to garner information. MATERIAL AND METHODS: A questionnaire was
      designed comprised of thirteen questions: 737 patients participated in the
      survey. The data were analysed based on population age, education, and number of
      radiological procedures received in the three years prior to survey. RESULTS: A
      majority of respondents (56.4%) did not know which modality uses ionizing
      radiation. 74.7% had never discussed with healthcare professionals the risk
      concerning their medical radiological procedures. 70.1% were not aware of the
      professionals that have expertise to discuss the use of ionizing radiation for
      medical purposes, and 84.7% believe it is important to have the radiation dose
      information stated in the medical report. CONCLUSION: Patients agree with new
      regulations that it is important to know the radiation level related to the
      medical exposure, but there is little awareness in terms of which modalities use
      X-Rays and the professionals and channels that can help them to better understand
      the exposure information. To plan effective communication, it is essential to
      devise methods and adequate resources for key professionals (medical physicists,
      radiologists, referring physicians) to convey correct and effective information.

PMID- 29195564
TI  - Adapted estimate of neural activity based on blood-oxygen-level dependent signal
      by a model-free spatio-temporal clustering analysis.
AB  - In this study, we detected brain activity by comparing the overall temporal
      response of the blood oxygen level referring to hemodynamic response with a
      modeled hemodynamic response (MHR). However, in a conventional analysis by
      statistical parametric mapping (SPM) method, the MHR is assumed to be a fixed
      response function, which may bias the conclusions about brain activation, such as
      the shapes of the response curve or the different response delays to stimuli.
      Therefore, to improve detection efficacy, we applied a spatio-temporal clustering
      analysis (sTCA) to determine the MHR, which is calculated from the prospective
      voxels with no a priori information about the experiment design. With the sTCA
      method, these prospective voxels are detected by the feature with the largest
      temporal clustering within which these voxels react simultaneously, irrespective
      of where the variant hemodynamic response occurs. This estimated MHR (eMHR) is
      then applied to search for brain activation. Preliminary results show that the
      eMHR signal response closely resembles the real signal response of the target
      area. Moreover, the activation detection using eMHR method is more sensitive for
      the human visual and motor tasks than that with the canonical hemodynamic
      response embedded in the SPM analysis as the default MHR (dMHR). The more precise
      location of brain activation made possible by the improved sensitivity should
      provide helpful information about the stimulation of neuron activity.

PMID- 29195565
TI  - Usefulness of a new online patient-specific quality assurance system for
      respiratory-gated radiotherapy.
AB  - PURPOSE: The accuracy of gated irradiation may decrease when treatment is
      performed with short "beam-on" times. Also, the dose is subject to variation
      between treatment sessions if the respiratory rate is irregular. We therefore
      evaluated the impact of the differences between gated and non-gated treatment on
      doses using a new online quality assurance (QA) system for respiratory-gated
      radiotherapy. METHODS: We generated dose estimation models to associate dose and
      pulse information using a 0.6 cc Farmer chamber and our QA system. During gated
      irradiation with each of seven regular and irregular respiratory patterns, with
      the Farmer chamber readings as references, we evaluated our QA system's accuracy.
      We then used the QA system to assess the impact of respiratory patterns on dose
      distribution for three lung and three liver radiotherapy plans. Gated and non
      gated plans were generated and compared. RESULTS: There was agreement within 1.7%
      between the ionization chamber and our system for several regular and irregular
      motion patterns. For dose distributions with measured errors, there were larger
      differences between gated and non-gated treatment for high-dose regions within
      the planned treatment volume (PTV). Compared with a non-gated plan, PTV D95% for
      a gated plan decreased by -1.5% to -2.6%. Doses to organs at risk were similar
      with both plans. CONCLUSIONS: Our simple system estimated the radiation dose to
      the patient using only pulse information from the linac, even during irregular
      respiration. The quality of gated irradiation for each patient can be verified
      fraction by fraction.

PMID- 29195566
TI  - Radiotherapy for non-malignant shoulder syndrome: Is there a risk for radiation
      induced carcinogenesis?
AB  - PURPOSE: To estimate the organ-specific probability for carcinogenesis following
      radiotherapy for non-malignant shoulder syndrome. METHODS: Photon-beam radiation
      therapy to 6 Gy for shoulder syndrome was simulated with a Monte Carlo code. An
      androgynous computational phantom representing a typical adult was used to
      calculate the radiation dose to out-of-field organs having a predilection for
      carcinogenesis. The organ-specific lifetime attributable risk (LAR) for out-of
      field cancer induction was estimated by the organ dose calculations and the
      proper risk factors introduced by the BEIR-VII report. The average dose (Dav) and
      organ equivalent dose (OED) of lung, which was partially included within the
      treatment volume, was found from 3d-conformal radiotherapy plans. The Dav and OED
      were used to estimate the lung cancer risk with a linear and mechanistic models,
      respectively. All risk assessments were made for 50- and 60-year-old male and
      female patients. RESULTS: Monte Carlo simulations resulted in an out-of-field
      organ dose range of 0.7-48.4 mGy. The LARs for out-of-field cancer induction were
      (1.4 * 10-4)% to (2.8 * 10-2)%. These probabilities were at least 403 times lower
      than the respective lifetime intrinsic risk (LIR) values. The Dav and OED of lung
      was up to 164.9 and 142.3 mGy, respectively. The LAR for developing lung
      malignancies varied from 0.11 to 0.18% by the model used and the patient's age
      and gender. The lung cancer risks were 36-64 times smaller than the LIRs.
      CONCLUSIONS: The estimated probabilities for developing malignancies due to
      radiotherapy for non-malignant shoulder syndrome are minor relative to the
      natural cancer occurrence rates.

PMID- 29195567
TI  - Review of technologies and procedures of clinical dosimetry for scanned ion beam
      radiotherapy.
AB  - In the last few years, the use of ions in radiation therapy is gaining interest
      and it is being considered medically necessary for a growing subset of tumours.
      Concurrently, the technologies involved in a particle therapy treatment are
      rapidly evolving, as well as the accuracy in the dose delivery in spite of the
      increased complexity. Since nowadays, the pencil beam scanning technique is
      showing very interesting features in terms of dose conformation and overall
      treatment outcome, the present review is intended to summarize the main
      procedures, detectors and tools adopted for the clinical dose verification. A
      list of dose measurements is provided, with the aim of being a valuable guidance
      for starting and future particle therapy facilities. Absorbed dose to water,
      relative dose, fluence and surrogates of the delivered dose are the main
      quantities measured by means of different detectors, specifically developed for
      point-like, 1D or 2D measurements. The dosimetric procedures are here categorized
      according to their purpose, distinguishing between system commissioning and
      clinical quality assurance. A separate discussion is dedicated to patient
      specific, in vivo and 4D dose verification, which aim at assessing the actual
      delivered dose. Together with the description of the currently used methods,
      challenges and perspectives toward an increasingly accurate and fast dose
      verification strategy are discussed.

PMID- 29195568
TI  - Editorial.

PMID- 29195570
TI  - Worldwide Trends in Multi-arterial Coronary Artery Bypass Grafting Surgery 2004
      2014: A Tale of 2 Continents.
AB  - Recent evidence shows that multi-arterial coronary artery bypass grafting (MABG)
      based on bilateral internal thoracic (BITA) or left internal thoracic (LITA) and
      radial artery (RA) improves long-term outcomes compared with single arterial
      coronary artery bypass grafting (SABG) (LITA + saphenous vein graft). How this
      evidence affected the worldwide use of MABG, if at all, is not well defined.
      Accordingly, we report 10-year temporal trends of MABG utilization from 2
      continents. A study population of 1,683,434 non-emergent, primary, isolated LITA
      based coronary artery bypass grafting (CABG) (>=2 grafts) patients was derived
      from the Society of Thoracic Surgeons (STS) (1,307,528 (79.5%) of 1,644,388
      isolated CABG; total 1179 centers) and the Australia New Zealand Cardiothoracic
      (ANZ) Databases (34,213 (87%) of 39,046 isolated CABG; 24 centers) between 2004
      and 2014. Patients were excluded based on the following: (1) no LITA, (2) if
      arterial grafts were other than RA or ITA, or (3) if grafting data were missing.
      The 3 MABG groups were LITA + RA, BITA, and BITA + RA, each with or without
      supplemental vein grafts. Grafting trends and their associated patient
      demographics were analyzed. SABG (89.3% STS, 51.4% ANZ) was the most common
      grafting strategy. MABG was most frequently accomplished by LITA + RA: (STS:
      6.1%; ANZ: 42.6%), followed by BITA: (STS: 4.1%; ANZ: 4.3%), while >=3 (BITA +
      RA) was rare in the STS (0.5%), but more common in ANZ (5.9%). In the STS,
      between 2004 and 2014, SABG rates systematically increased from 85.2% to 91.7%,
      BITA grafting was essentially unchanged from 3.6% to 4.3%, while RA use decreased
      systematically from 10.5% to 3.7%. In the ANZ, SABG rates increased from 17.3% to
      51.4%, BITA grafting decreased from 6.3% to 3.6%, while RA grafting decreased
      from 65.8% to 39.0%. Compared with SABG patients, BITA patients were younger
      (STS: median age 59 vs 66, P < 0.001; ANZ: mean age 62 vs 68, P < 0.001),
      predominately male (STS: 84% vs 73%, P < 0.001; ANZ: 86% vs 79%, P < 0.001), less
      obese (body mass index >30 kg/m2) in STS (37% vs 42%, P < 0.001), more obese in
      ANZ (33% vs 32%, P = 0.001), and less diabetic (STS: 26% vs 43%, P < 0.001; ANZ:
      25% vs 37%, P < 0.001), whereas RA patients were intermediate in age (STS: 61;
      ANZ: 65), in male sex (STS: 82%; ANZ: 81%), in the prevalence of diabetes (STS:
      40%; ANZ: 34%), and were most obese (STS: 47%; ANZ: 34%). A decade-long analysis
      of STS data reveals a counterintuitive decline in the use (driven by decreasing
      RA use) of MABG: a potentially superior grafting strategy compared with SABG. In
      contra distinction, the smaller but growing ANZ data document a distinctly
      different CABG practice pattern, with a higher MABG utilization rate, but a
      similarly declining RA use. The reasons for these practice patterns and declining
      MABG are likely diverse and require further assessment.

PMID- 29195571
TI  - Impact of Discordant Views in the Management of Descending Thoracic Aortic
      Aneurysm.
AB  - Thoracic endovascular aortic repair has a lower perceived risk than open surgical
      repair and has become an increasingly popular alternative. Whether general
      consensus exists regarding candidacy for either operation among open and
      endovascular specialists is unknown. A retrospective review of isolated
      descending thoracic aortic aneurysm at our institution between January 2005 and
      October 2015 was performed, excluding trauma and dissection. Two cardiac
      surgeons, 2 cardiovascular surgeons, 1 vascular surgeon, and 1 interventional
      radiologist gave their preference for open vs endovascular repair. Interobserver
      agreement was assessed with the kappa coefficient. k-means clustering
      agnostically grouped various patterns of agreement. The mean rating was predicted
      using least absolute shrinkage and selection operator regression. Negative
      binomial regression predicted the discrepancy between our panel of raters and the
      historical operation. Generalized estimating equation modeling was then used to
      evaluate the association between the extent of discrepancy and the adverse
      perioperative outcome. There were 77 patients with preoperative imaging studies.
      Pairwise interobserver agreement was only fair (median weighted kappa 0.270
      [interquartile range 0.211-0.404]). Increasing age and proximal neck length
      predicted an increasing preference for thoracic endovascular aortic repair in our
      panel; larger proximal neck diameter predicted a general preference for open
      surgical repair. Increasing proximal neck diameter predicted a larger discrepancy
      between our panel and the historical operation. Greater discrepancy was
      associated with adverse outcome. Substantial disagreement existed among our
      panel, and an exploratory analysis of the effect of increasing discrepancy
      demonstrated an association with adverse perioperative outcome. An investigation
      of the effect of a thoracic aortic team with open and endovascular specialists is
      warranted.

PMID- 29195572
TI  - Carbon Dioxide Insufflation During Cardiac Surgery: A Meta-analysis of Randomized
      Controlled Trials.
AB  - Despite the widespread use of carbon dioxide insufflation (CDI) in cardiac
      surgery, there is still paucity of evidence to prove its benefit in terms of
      neurologic protection. Therefore, we conducted a meta-analysis of available
      randomized controlled trials comparing CDI vs standard de-airing maneuvers.
      Electronic searches were performed to identify relevant randomized controlled
      trials. Primary outcomes investigated were postoperative stroke, neurocognitive
      deterioration, and in-hospital mortality. Risk difference (RD) was used as
      summary statistic. Pooled estimates were obtained by means of random-effects
      model to account for possible clinical diversity and methodological variation
      between studies. Eight studies were identified with 668 patients randomized to
      CDI (n = 332) vs standard de-airing maneuvers (n = 336). In-hospital mortality
      was 2.1% vs 3.0% in the CDI and control group, respectively (RD 0%; 95%
      confidence interval [CI] -2% to 2%; P = 0.87; I2 = 0%). Incidence of stroke was
      similar between the 2 groups (1.0% vs 1.2% in the CDI and control group,
      respectively; RD 0%; 95% CI -1% to 2%; P = 0.62; I2 = 0%). Neurocognitive
      deterioration rate was 12% vs 21% in the CDI and control group, respectively, but
      this difference was not statistically significant (RD: -7%; 95% CI -0.22% to 8%;
      P = 0.35; I2 = 0%). The present meta-analysis did not find any significant
      protective effect from the use of CDI when compared with manual de-airing
      maneuvers in terms of clinical outcomes, including postoperative neurocognitive
      decline.

PMID- 29195573
TI  - Complications After Self-expanding Transcatheter or Surgical Aortic Valve
      Replacement.
AB  - Procedural complications following transcatheter aortic valve replacement (TAVR)
      or surgical aortic valve replacement (SAVR) are usually reported as retrospective
      analyses. We report the first comparison of complications following SAVR or self
      expanding TAVR from a prospectively randomized study of high-risk SAVR patients.
      Three hundred ninety-five TAVR and 402 SAVR patients were prospectively enrolled
      and randomized 1:1 to TAVR with a CoreValve bioprosthesis or a surgical
      bioprosthetic valve. The rates of major procedural and vascular complications
      occurring (periprocedurally (0-3 days) and early (4-30 days)) were compared for
      TAVR vs SAVR patients. All-cause mortality, stroke, myocardial infarction, and
      major infection were similar in both periods post procedure. Within 0-3 days, the
      major vascular complication rate was significantly higher with TAVR (P = 0.003).
      Life-threatening or disabling bleeding (P < 0.001), encephalopathy (P = 0.02),
      atrial fibrillation (P < 0.001), and acute kidney injury (P < 0.001) were
      significantly higher with SAVR. Non-iliofemoral TAVR approaches had a higher
      incidence of major or life-threatening or disabling bleeding at 0-3days (P <
      0.05). Procedural complications unique to TAVR included coronary occlusion 0.5%
      (2) and TAVR pop outs 2.8% (11) with no valve embolizations. Pop outs were
      similar between iliofemoral 2.8% (9/324) and non-iliofemoral approaches 3.0%
      (2/66). Procedural complications unique to SAVR included aortic dissection 0.8%
      (3/357) and injury to other heart structures 2.0% (7/357). The procedural
      complication profiles of TAVR and SAVR are unique. Intraoperative deaths were
      seen in TAVR only. Mortality at 3 and 30 days was similar. The higher incidence
      of some complications likely reflects the greater invasiveness of SAVR in this
      aged high-risk population.

PMID- 29195574
TI  - Outcomes of Surgery for Mixed Total Anomalous Pulmonary Venous Drainage in
      Children.
AB  - Total anomalous pulmonary venous drainage (TAPVD) is an uncommon cardiac defect
      in children. The mixed subset accounts for 5%-10% of the TAPVD and is variable in
      its anatomy. The outcomes associated with this subset of patients are rarely
      reported. A retrospective review of all patients with mixed TAPVD undergoing
      repair at a single institution (1984-2014) was conducted. A descriptive analysis
      was performed. Twenty-four patients underwent repair for mixed TAPVD (6
      univentricular physiology, 18 biventricular physiology). The mixed TAPVD anatomy
      included 8 patients in group I (2 + 2 veins), 11 patients in group II (3 + 1
      veins), and 5 patients in group III (atypical). Preoperative pulmonary venous
      obstruction occurred in 8 patients (33%). The median age at repair was 2.2 months
      (range 2 days to 3 years) and median weight was 4.2 kg (range 1.9 to 12.5 kg).
      Operative mortality was 13% (3 of 24), 33.3% (2 of 6) for patients with
      univentricular physiology, and 5.6% (1 of 18) for patients with biventricular
      physiology. There have been no operative deaths in the biventricular group since
      1997 (n = 11). Survival at 30-days was 83% +/- 15% (95% confidence interval: 27%
      97%) and 94% +/- 5% (95% confidence interval: 67%-99%) for the univentricular and
      biventricular groups, respectively. Reoperation for recurrent pulmonary venous
      obstruction was required in 2 patients (8.3%) where the sutureless technique was
      used. The average follow-up after surgery was 9.3 +/- 6.4 years (5 months to 21
      years), and all surviving patients were asymptomatic. Mixed TAPVD can be repaired
      with good results in children, particularly in those undergoing biventricular
      repair.

PMID- 29195575
TI  - Twenty-Five Year Outcomes of the Lateral Tunnel Fontan Procedure.
AB  - The objective of this study was to characterize late outcomes of the lateral
      tunnel (LT) Fontan procedure. The outcomes of all patients who underwent an LT
      Fontan procedure in Australia and in New Zealand were analyzed. Original files
      were reviewed and outcomes data were obtained through a binational registry.
      Between 1980 and 2014, a total of 301 patients underwent an LT Fontan procedure
      across 6 major centers. There were 13 hospital mortalities, 21 late deaths, 8
      Fontan conversions and revisions, 8 Fontan takedowns, and 4 heart
      transplantations. Overall survival at 15 and 25 years was 90% (95% confidence
      interval [CI]: 86%-93%) and 80% (95% CI: 69%-91%), respectively. Protein-losing
      enteropathy or plastic bronchitis was observed in 14 patients (5%). Freedom from
      late failure at 15 and 25 years was 88% (95% CI: 84%-92%) and 82% (95% CI: 76%
      87%), respectively. Independent predictors of late Fontan failure were prolonged
      pleural effusions post Fontan operations (hazard ratio [HR] 3.06, 1.05-8.95, P =
      0.041), age >7 years at Fontan (vs 3-5 years, HR 9.7, 2.46-38.21, P = 0.001) and
      development of supraventricular tachycardia (HR 4.67, 2.07-10.58, P < 0.001).
      Freedom from tachy- or bradyarrhythmias at 10 and 20 years was 87% (95% CI: 83%
      91%) and 72% (95% CI: 66%-79%), respectively. Thromboembolic events occurred in
      45 patients (16%, 26 strokes), and freedom from symptomatic thromboembolism at 10
      and 20 years was 93% (95% CI: 89%-96%) and 80% (95% CI: 74%-86%), respectively.
      Over a 25-year period, the LT technique has achieved excellent late survival. As
      this population ages, it is at an increasing risk of failure and adverse events.
      We are likely to see an increasing proportion requiring heart transplantation and
      late reintervention.

PMID- 29195576
TI  - Histologic Evaluation of Explanted Tissue-Engineered Bovine Pericardium
      (CardioCel).
AB  - CardioCel is a bovine pericardium that is subjected to a novel anticalcification
      tissue-engineering process. We present the histopathologic findings of human
      explants of CardioCel that were used in operations for congenital heart disease
      in children. Six explants were identified from 140 patients undergoing CardioCel
      implants from October 2012 to March 2015. CardioCel explants were evaluated
      histologically using hematoxylin and eosin, Masson trichrome, and
      immunohistochemical staining. A variable inflammatory response was seen in the
      surrounding native tissue, but not within the CardioCel graft in any of the
      explants. A neointimal layer of varying thickness developed on the visceral
      surface of 5 CardioCel explants with endothelialization of the longest duration
      explant. A granulation tissue layer developed on the parietal surface of the
      graft (consistently thicker than the neointima). Maintained collagen fiber
      architecture (laminated) and variable fibroblastic invasion (which increased with
      the age of the implant) were identified in all 6 cases. Scattered capillary
      vessels were noted in the majority of the explants with new collagen fibers in
      one, suggesting early remodeling. Calcium was seen in 1 explant at the interface
      of the graft and inflammatory response on its parietal surface. Evidence of graft
      remodeling was noted in the majority of the explants without inflammatory cells
      or calcification within the explanted graft material. A noticeable feature was
      the differential thickness of the host reaction to the parietal compared with the
      visceral surface of the graft. We will continue to evaluate CardioCel as a
      cardiovascular substitute for extracardiac and intracardiac reconstructions.

PMID- 29195577
TI  - Perspectives on Managing Solitary Pulmonary Nodules: A Survey of Primary Care
      Physicians.
AB  - Primary care physicians (PCPs) may be involved in the evaluation of solitary
      pulmonary nodules (SPNs) detected through lung cancer screening. Little is known
      about their perspectives on the management or the referral of SPN. Using the
      American Medical Association's Physician Masterfile, we randomly surveyed 1384
      PCPs between January and October 2015 with an 18% response rate. A subset
      analysis was performed on SPN management and referral practices of PCP. These
      results and those relating to practice characteristics were compared between
      family practice and internal medicine physicians. Responders and nonresponders
      did not differ by demographic characteristics. A total of 137 (55.5%) PCPs
      reported feeling confident in managing the workup of imaging-detected SPN.
      However, only 53 PCPs (21.3%) were inclined to manage the evaluation and follow
      up of SPN. There was no significant difference between family practice and
      internal medicine physicians with regard to years in practice, size of practice,
      or referral to specialists. Family practitioners and internists similarly
      disagreed or were neutral to self-managing SPN (P = 0.60). Internists were twice
      as likely to express confidence as family practitioners (odds ratio 1.95, 95%
      confidence interval 1.09-3.48). Among all PCPs, 75.4% would refer management of
      these patients to a pulmonologist, 28.9% to a surgeon, and 24.2% to an
      oncologist. Confidence did not predict lung cancer screening practices. Although
      more than half of PCPs expressed confidence in the workup of SPN, most preferred
      referral to specialists. Additional research is needed to understand barriers to
      PCP management of incidental SPN in the effort to facilitate lung cancer
      screening.

PMID- 29195579
TI  - Primary Pulmonary Vein Leiomyosarcoma With Left Atrial Extension.
AB  - Leiomyosarcoma (LMS) is a mesenchymal tumor originating from the smooth muscle
      cells. LMS of the great vessels accounts for 60% of cases, with inferior vena
      cava being the most common site. Pulmonary vein LMS is an extremely rare subset
      that was first reported in 1939. LMS is an aggressive tumor, making surgical
      resection the treatment of choice. Herein, we present a rare case of pulmonary
      vein LMS extending into the left atrium, which was resected.

PMID- 29195578
TI  - Programmed Death Cell Ligand 1 (PD-L1) Is Associated With Survival in Stage I Non
      Small Cell Lung Cancer.
AB  - Programmed cell death ligand (PD-L1) has been studied as a predictive
      immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and
      in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically
      resected pathologic stage I non-small cell lung cancer. Pathologic specimen from
      113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79
      adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in
      the tumor and in the TIMs using immunohistochemistry and image analysis.
      Statistics included recursive partitioning, univariable, multivariable, and
      Kaplan-Meier analyses. Patients whose tumors expressed <4.7% PD-L1 (N = 87)
      experienced significantly better overall survival (OS) (P = 0.001) than patients
      with PD-L1 >4.7% (N = 26). Patients with PD-L1 expression in macrophages <6.3% (N
      = 24) also experienced significantly better (P = 0.005) OS than patients with
      >6.3% (N = 89). The best outcomes were observed in patients with low PD-L1
      expression in both tumor and macrophages with 5-year OS of 94% (N = 17).
      Contrarily, patients with high PD-L1 expression in both tumor and macrophages
      experienced 5-year OS of 20% (N = 19). Low PD-L1 expression in the tumor and in
      the TIMs was independently associated with survival in multivariable analysis (P
      = 0.000 and P = 0.030, respectively). Lower PD-L1 % expression in the tumor and
      in the TIMs seems to be associated with significantly better OS in surgically
      resected stage I lung cancer. Additional studies are needed to validate PD-L1 as
      a prognostic biomarker in lung cancer and to study the mechanisms of intratumoral
      immune response.

PMID- 29195581
TI  - APIC's strategic partners: Committed to transformational change.

PMID- 29195580
TI  - Thoracoscopic Surgery for a Congenital Bronchoesophageal Fistula With Pulmonary
      Sequestration in an Adult Woman.
AB  - A congenital bronchoesophageal fistula with pulmonary sequestration is rare in
      adults. Here, we report the case of an adult woman having congenital
      bronchoesophageal fistula with intralobar pulmonary sequestration who
      successfully underwent thoracoscopic resection and showed a good postoperative
      course.

PMID- 29195582
TI  - Microbial profile and characterization of blue bulb manual suction devices used
      to promote airway clearance in newborns in intrapartum and postpartum units.
AB  - BACKGROUND: Newborns are suctioned with a blue bulb manual suction device to
      remove naso-oropharyngeal secretions and promote airway clearance. This study
      identifies and discusses the microbial profile and characterization of the bulb
      used in newborns on intrapartum and postpartum units. METHODS: This was a
      descriptive study with convenience sampling of a total of 50 bulbs used in
      cesarean births, vaginal births, and on the postpartum unit. The bulbs were
      tested for microbial growth, and the percentages of contaminated bulbs were
      calculated. The chi2 test was used to compare the proportion of bulbs with
      microbial growth by route of birth among bulbs sampled from the intrapartum unit.
      RESULTS: Microbial profile and characterization identified a total of 57
      different gram-positive cocci and rods and gram-negative rods. Among 50 bulbs
      cultured, bacterial growth was present in 42% of the bulbs, and Escherichia coli
      was identified in 55% of the gram-negative rod isolates. The chi2 test comparing
      vaginal and cesarean bulbs showed a statistically significant difference in the
      percentages of contaminated bulbs for any growth (P = .023) and for any
      Staphylococcus spp (P = .050). CONCLUSIONS: New empirical evidence confirms the
      bulb is a potential bacterial reservoir and poses a potential health risk for
      nosocomial infections for newborns. Further studies are needed to identify
      bacterial transmission, newborn outcomes, bactericidal bulb cleaning methods, and
      quality and safe suction practices.

PMID- 29195583
TI  - Risk factors for methicillin-resistant Staphylococcus aureus colonization in the
      neonatal intensive care unit: A systematic review and meta-analysis.
AB  - CONTEXT: Methicillin-resistant Staphylococcus aureus (MRSA) causes a significant
      burden of illness in neonatal intensive care units (NICUs) worldwide. Identifying
      infants colonized with MRSA has become an important infection control strategy to
      interrupt nosocomial transmission. OBJECTIVE: Assess risk factors for MRSA
      colonization in NICUs via a systematic review and meta-analysis. DATA SOURCES:
      MEDLINE, Embase, Web of Science, and The Cochrane Library databases were searched
      from inception through September 2015. STUDY SELECTION: Studies reporting risk
      factors for MRSA colonization using noncolonized controls in subspecialty level
      III or IV NICUs were included. DATA EXTRACTION: Two authors independently
      extracted data on MRSA colonization risk factors, study design, and MRSA
      screening methodology. RESULTS: Eleven articles were included in the systematic
      review, with 10 articles analyzed via meta-analysis. MRSA colonization was
      associated with gestational age <32 weeks (odds ratio [OR], 2.67; 95% confidence
      interval [CI], 1.35-5.27; P = .01) and birth weight <1,500 g (OR, 2.63; 95% CI,
      1.25-5.55; P = .01). Infant sex (P = .21), race (P = .06), inborn status (P =
      .09), and delivery type (P = .24) were not significantly associated with
      colonization. CONCLUSIONS: Very preterm and very-low birth weight infants were
      identified as having an increased risk for MRSA colonization on meta-analysis.
      Multifaceted infection prevention strategies should target these high-risk
      infants to reduce MRSA colonization rates in NICUs.

PMID- 29195584
TI  - Health care-associated infections studies project: An American Journal of
      Infection Control and National Healthcare Safety Network data quality
      collaboration.
AB  - This case study is part of a series centered on the Centers for Disease Control
      and Prevention/National Healthcare Safety Network (NHSN) health care-associated
      infection (HAI) surveillance definitions. This specific case study focuses on the
      definitions and protocols used to make HAI infection determinations, such as the
      infection window period and secondary bloodstream infection attribution period.
      The case reflects the real-life and complex patient scenarios that infection
      preventionists (IPs) face when identifying and reporting HAIs to NHSN. The intent
      of the case study series is to foster standardized application of the NHSN HAI
      surveillance definitions among IPs and encourage accurate determination of HAI
      events. An online survey link is provided where participants may confidentially
      answer questions related to the case study and receive immediate feedback in the
      form of correct answers and explanations and rationales. Details of the case
      study, answers, and explanations have been reviewed and approved by NHSN staff.
      We hope that participants take advantage of this educational offering and thereby
      gain a greater understanding of NHSN HAI surveillance definitions.

PMID- 29195585
TI  - Journal Club: Commentary on "Risk factors for MRSA colonization in the neonatal
      ICU: A systematic review and meta-analysis".

PMID- 29195586
TI  - The heroic fictional microbe and the real heroic vaccine.

PMID- 29195587
TI  - Risk factors for bacteremia with extended-spectrum beta-lactamase production in
      positive Escherichia coli bacteremia in a pediatric setting.

PMID- 29195588
TI  - Characteristics and clinical treatment of tobacco smokers enrolled in a VA
      substance use disorders clinic.
AB  - Individuals with a substance use disorder (SUD) diagnosis are more than twice as
      likely to smoke cigarettes as the general population. Emerging research has
      suggested that treating a substance use disorder simultaneously with tobacco use
      leads to a higher rate of treatment success for both substances. Despite this,
      substance use treatment protocols tend not to focus on tobacco use; in fact,
      traditional substance use treatments often discourage patients from attempting to
      quit smoking. One rationale is that patients may not be motivated to quit
      smoking. In the current study, data from veterans enrolled in outpatient
      treatment for a SUD were examined to assess for general characteristics of
      smokers as compared to non-smokers as well as to examine motivation to quit
      smoking. Baseline (i.e., pre-treatment) data from 277 Veterans were used. Charts
      of smokers in the SUD clinic (SUDC) were reviewed to assess how smoking is
      handled by SUDC providers, and if smokers attempt cessation. Of 277, 163 (59%)
      SUDC patients reported that they currently smoke cigarettes (M=16.3 cigarettes
      per day, SD=11.1). Smokers in the clinic reported greater general impairment than
      nonsmokers on the Short Index of Problems, F(1248)=8.9, p=0.003, as well as
      greater specific impairment: Physical Problems, F(1258)=13.5, p=0.000;
      Interpersonal Problems, F(1262)=5.6, p=0.019; Intrapersonal Problems,
      F(1260)=6.5, p=0.011, and Social Responsibility, F(1262)=14.7, p=0.000. Smokers
      in the sample were marginally more anxious than their non-smoking counterparts as
      measured by the GAD-7, F(1254)=4.6, p=0.053, though they were not significantly
      more depressed (p=0.19). On a 1-10 scale, smokers reported moderate levels of
      importance (M=5.4, SD=3.1), readiness (M=5.6, SD=3.2), and confidence (M=5.0,
      SD=3.0) regarding quitting smoking. Review of smokers' medical records reveal
      that while SUDC providers assess tobacco use at intake (90%) and offer treatment
      (86.5%), a substantially small portion of smokers attempt cessation (41.1%) while
      enrolled in SUDC. Moreover, no patients were enrolled in smoking-specific
      behavioral interventions while in SUDC, though 78 patients did obtain nicotine
      replacement or another smoking cessation medication (41% were prescribed by a
      SUDC provider). Contrary to the belief that treatment-seeking substance users are
      not motivated to quit smoking, these preliminary analyses demonstrate that
      Veterans were at least contemplating quitting smoking while they were enrolled in
      substance use treatment. Further, there is evidence that cigarette smokers have
      greater impairment caused by substance use, suggesting that this subgroup is of
      particular high need. Specific treatment recommendations are discussed, including
      how behavioral health providers in SUD clinics may be better able to capitalize
      on patients' moderate motivation to quit at intake.

PMID- 29195589
TI  - Factors associated with naloxone administration in an opioid dependent sample.
AB  - INTRODUCTION: Naloxone is a safe and effective antidote for reversing opioid
      overdose. Layperson administration of naloxone is increasingly common, yet little
      is known about demographic and clinical factors associated with opioid users'
      likelihood of having administered naloxone to another opioid user who had
      overdosed. We examined predictors of reported naloxone administration in the past
      year. METHODS: Four hundred and sixty-eight patients were interviewed upon
      admission to brief, inpatient opioid detoxification between May and December of
      2015. Between group differences were tested using t-tests for differences in
      means and chi2-tests for differences in counts. RESULTS: Participants averaged
      32years of age, 28.9% were female, and 86.8% were White. Most (86.8%) reported
      detoxifying from heroin, 69.0% had injected drugs in the last 30days. One sixth
      (n=68) of those detoxifying from heroin, but none of those detoxifying from other
      opioids (n=62) had administered naloxone in the past year. Among the small number
      of Black/African American participants (n=20), none had administered naloxone,
      although 90% were heroin users. Respondents were more likely to have administered
      naloxone if they reported recent injection drug use (IDU), had a history of
      overdose, or witnessed an overdose in the past year (ps<0.05), even though less
      than one-third of bystanders of overdose reported administering naloxone.
      CONCLUSIONS: Higher opioid-related mortality risk (heroin use, IDU, past
      overdose) was associated with greater likelihood of reported naloxone
      administration in the past year. The non-use of naloxone among certain groups
      prescription pill users and Blacks-was unexpected.

PMID- 29195590
TI  - Age differences in outcomes among patients in the "Stimulant Abuser Groups to
      Engage in 12-Step" (STAGE-12) intervention.
AB  - : Emerging adults (roughly 18-29years) with substance use disorders can benefit
      from participation in twelve-step mutual-help organizations (TSMHO), however
      their attendance and participation in such groups is relatively low. Twelve-step
      facilitation therapies, such as the Stimulant Abuser Groups to Engage in 12-Step
      (STAGE-12), may increase attendance and involvement, and lead to decreased
      substance use. AIMS: Analyses examined whether age moderated the STAGE-12 effects
      on substance use and TSMHO meeting attendance and participation. DESIGN: We
      utilized data from a multisite randomized controlled trial, with assessments at
      baseline, mid-treatment (week 4), end-of-treatment (week 8), and 3- and 6- months
      post-randomization. PARTICIPANTS: Participants were adults with DSM-IV diagnosed
      stimulant abuse or dependence (N=450) enrolling in 10 intensive outpatient
      substance use treatment programs across the U.S. ANALYSIS: A zero-inflated
      negative binomial random-effects regression model was utilized to examine age-by
      treatment interactions on substance use and meeting attendance and involvement.
      FINDINGS: Younger age was associated with larger treatment effects for stimulant
      use. Specifically, younger age was associated with greater odds of remaining
      abstinent from stimulants in STAGE-12 versus Treatment-as-Usual; however, among
      those who were not abstinent during treatment, younger age was related to greater
      rates of stimulant use at follow-up for those in STAGE-12 compared to TAU. There
      was no main effect of age on stimulant use. Younger age was also related to
      somewhat greater active involvement in different types of TSMHO activities among
      those in STAGE-12 versus TAU. There were no age-by-treatment interactions for
      other types of substance use or for treatment attendance, however, in contrast to
      stimulant use; younger age was associated with lower odds of abstinence from non
      stimulant drugs at follow-up, regardless of treatment condition. These results
      suggest that STAGE-12 can be beneficial for some emerging adults with stimulant
      use disorder, and ongoing assessment of continued use is of particular
      importance.

PMID- 29195591
TI  - Variability in motivational interviewing adherence across sessions, providers,
      sites, and research contexts.
AB  - Providers' adherence in the delivery of behavioral interventions for substance
      use disorders is not fixed, but instead can vary across sessions, providers, and
      intervention sites. This variability can substantially impact the quality of
      intervention that clients receive. However, there has been limited work to
      systematically evaluate the extent to which substance use intervention adherence
      varies from session-to-session, provider-to-provider, and site-to-site. The
      present study quantifies the extent to which adherence to Motivational
      Interviewing (MI) for alcohol and drug use varies across sessions, providers, and
      intervention sites and compares the extent of this variability across three
      common MI research contexts that evaluate MI efficacy, MI effectiveness, and MI
      training. Independent raters coded intervention adherence to MI from 1275
      sessions delivered by 216 providers at 15 intervention sites. Multilevel models
      indicated that 57%-94% of the variance in MI adherence was attributable to
      variability between sessions (i.e., within providers), while smaller proportions
      of variance were attributable to variability between providers (3%-26%) and
      between intervention sites (0.1%-28%). MI adherence was typically lowest and most
      variable within contexts evaluating MI training (i.e., where MI was not protocol
      guided and delivered by community treatment providers) and, conversely, adherence
      was typically highest and least variable in contexts evaluating MI efficacy and
      effectiveness (i.e., where MI was highly protocolized and delivered by trained
      therapists). These results suggest that MI adherence in efficacy and
      effectiveness trials may be substantially different from that obtained in
      community treatment settings, where adherence is likely to be far more
      heterogeneous.

PMID- 29195592
TI  - Understanding abuse of buprenorphine/naloxone film versus tablet products using
      data from ASI-MV(r) substance use disorder treatment centers and RADARS(r) System
      Poison Centers.
AB  - OBJECTIVES: The objectives were to examine the abuse prevalence and route-of
      administration (ROA) profiles of sublingual buprenorphine/naloxone combination
      (BNX) film in comparison with the BNX tablet and to identify clinically-relevant
      subgroups of patients or geographic patterns. METHODS: Between Q1 2015 through Q3
      2015, data were collected from two major surveillance systems: (1) assessment of
      individuals in substance use disorder (SUD) treatment collected from the National
      Addictions Vigilance Intervention and Prevention Program (NAVIPPRO(r)) ASI-MV(r)
      system and (2) intentional abuse/misuse exposures in the RADARS(r) System Poison
      Center Program. Poisson regression models were tailored to each system's data
      characteristics by population (all SUD treatment patients, US census) and
      adjusted for prescription volume. Effects of gender, race, age and US region as
      well as ROA profile were examined. RESULTS: For the ASI-MV study, 45,695
      assessments of unique adults evaluated for substance use problems were collected.
      The abuse rate unadjusted for prescription volume of BNX tablet formulation was
      2.64 cases/100 ASI-MV respondents versus 7.01 cases for the film formulation
      (RR=0.390, p<0.001). Prescription-adjusted abuse, however, was greater for the
      tablet version (0.47 abuse cases/100 ASI-MV respondents/100,000 dosage units
      compared with 0.38 for the film) (RR=1.25, p<0.001). Results among the US
      population from the RADARS System Poison Center Program data revealed a similar
      pattern; population rates for film abuse (0.0364) were greater than for tablet
      (0.0161), while prescription-adjusted rates were greater for tablet (0.2114) than
      for film (0.1703) per 100,000 prescriptions. ASI-MV ROA analyses indicated less
      abuse of the film by any alternate route, insufflation or injection than the
      tablet. Poison center data found more injection of tablets than film, although
      insufflation was not significantly different. CONCLUSIONS: On a prescription
      adjusted basis, overall abuse of the BNX tablet is greater than that of the
      sublingual film formulation. For those who continue to abuse BNX, use by
      alternate ROAs was, in general, lower for the film.

PMID- 29195594
TI  - Duration of therapy - Does it matter?: A systematic review and meta-regression of
      the duration of psychosocial treatments for alcohol use disorder.
AB  - BACKGROUND: The recommendations in clinical guidelines for duration of therapy
      for alcohol use disorder (AUD) are based on consensus decisions. In reality, we
      do not know the optimal duration of an alcohol treatment course. METHODS: A
      systematic review and meta-regression of randomized controlled trials of
      psychosocial treatment in alcohol outpatient treatment centers. The population
      consisted of adults suffering from AUD, treated in an outpatient facility with at
      least two sessions of therapy. Meta-regression analysis was performed with
      treatment outcome as a function of duration of therapy across studies. Treatment
      outcome was defined as long-term alcohol use measured in percentage of days
      abstinent (PDA), percentage of heavy days drinking (PHD), and/or proportion of
      participants abstinent (ABS). RESULTS: 48 studies encompassing 8984 participants.
      Mean planned duration of therapy: 18 (8-82) weeks and 14 (2-36) sessions. Mean
      actual attended sessions: 9 (1-26). Mean follow-up time: 43 (8-104) weeks with a
      mean of 6 (2-18) research assessments. Neither planned weeks, duration of
      sessions, frequency of sessions per week, nor actual attended sessions were
      associated with long-term alcohol use outcomes. However, frequency of research
      assessments was positively associated with PDA and PHD. CONCLUSION: No
      associations between long-term alcohol use outcomes and planned or actual
      attended duration of psychosocial treatment in outpatient care. Research
      assessments and, accordingly, the research project in itself may influence
      outcome in studies of psychosocial treatment for alcohol use disorder.

PMID- 29195593
TI  - Gender and ethnic differences in primary care patients' response to computerized
      vs. in-person brief intervention for illicit drug misuse.
AB  - This study is a secondary analysis from a randomized clinical trial of
      computerized vs. in-person brief intervention (BI) for illicit drug misuse among
      adult primary care patients (N=359; 45% Female; 47% Hispanic) with moderate-risk
      illicit drug misuse as measured by the World Health Organization's Alcohol,
      Smoking, and Substance Involvement Screening Test (ASSIST). This study examined
      differences in response to the two brief intervention strategies (both based on
      motivational interviewing) on the basis of gender and ethnicity, comparing non
      Hispanic males, non-Hispanic females, Hispanic males, and Hispanic females.
      Participants were assessed at baseline, 3-, 6-, and 12-month follow-up with the
      ASSIST. Trajectories in Global Continuum of Illicit Drug Risk Scores were
      examined using a generalized linear mixed model. There were significant
      differences in response to computerized vs. in-person BI over time on the basis
      of gender-ethnic subgroups (Gender*Ethnicity*Condition*Time interaction; p=0.03),
      with Hispanic males tending to respond more favorably to the computerized BI and
      Hispanic females tending to respond more favorably to the in-person BI. There was
      no clear differentiation in response to the two BIs among non-Hispanic males,
      while among non-Hispanic females the pattern of change converged following
      baseline differences. Consideration of gender and ethnic differences in future
      studies of BI is warranted.

PMID- 29195596
TI  - Group-based treatment of opioid use disorder with buprenorphine: A systematic
      review.
AB  - BACKGROUND: Opioid use disorder (OUD) has become a public health crisis in the
      U.S., and there is a need to develop effective clinical treatment strategies.
      Coupling buprenorphine/naloxone (B/N) maintenance with counseling is encouraged
      as a best practice, yet the efficacy research on individual counseling in B/N
      based Office-Based Opioid Treatment (OBOT) has been equivocal to date. In
      contrast, models for integrating B/N prescribing through group-based counseling
      could potentially have a differential impact, yet no systematic reviews have
      focused on examining the extent of the literature on group-based models of B/N
      delivery. METHODS: We conducted a systematic literature review to identify
      existing studies characterizing the different formats of Group-Based Opioid
      Treatment (GBOT), which we defined as the coupling of B/N prescribing with
      required office-based group counseling. Using this definition of GBOT, B/N
      prescribing could occur either concurrently during a medical visit with group
      counseling (i.e., Shared Medical Appointment) or asynchronously (i.e., Group
      Psychotherapy). We assessed for all available scientific literature reporting on
      the feasibility, acceptability and/or efficacy of these different forms of GBOT.
      The systematic review protocol used PRISMA standards. RESULTS: We included 10
      peer-reviewed, full-text articles and 5 conference abstracts of office-based
      opioid use disorder treatment that reported data on the feasibility,
      acceptability, and efficacy of Group-Based Opioid Treatment with B/N. Of the ten
      full-text articles we included 4 studies describing a shared medical appointment
      (SMA) model and 6 studies describing a group psychotherapy model. Of these
      studies, all were low in quality due to study design and only three were
      randomized controlled trials. No studies were appropriately designed to
      rigorously compare the efficacy of a GBOT approach (i.e., B/N prescribing with
      required group-based counseling) versus B/N prescribing with required individual
      counseling; nor were they designed for rigorous comparison with medication
      management alone. Nevertheless, most studies reported on the feasibility and
      acceptability of various models representative of a GBOT approach. CONCLUSION:
      The small number of studies and study design limited the conclusions that could
      be drawn about the feasibility, acceptability, and efficacy of group-based B/N
      treatment. More research is needed to determine whether benefits exist of GBOT
      with B/N.

PMID- 29195595
TI  - Factors associated with victimization in dual diagnosis patients.
AB  - BACKGROUND: Patients with a substance use disorder and co-occurring mental
      disorder are prone to victimization. There is a lack of research identifying
      variables related to violent and property victimization in this high risk group.
      The aim of this study was to identify factors associated with violent and
      property victimization in male and female dual diagnosis patients in order to
      identify targets for prevention. METHODS: In a cross-sectional study,
      victimization and demographic, clinical and psychological characteristics were
      assessed in 243 treatment-seeking patients with dual diagnosis. Patients were
      recruited in an addiction-psychiatry clinic and an allied outpatient care
      facility in Amsterdam, The Netherlands. RESULTS: In a multiple logistic
      regression analysis, violent victimization was independently associated with
      younger age, female gender, violent offending and a self-sacrificing and overly
      accommodating interpersonal style (p<0.001; chi2=108.83, d.f.=8, R2=0.49) in dual
      diagnosis patients. In male patients, violent victimization was independently
      associated with younger age, violent offending and a self-sacrificing and overly
      accommodating interpersonal style (p<0.001; chi2=91.90, d.f.=7, R2=0.56). In
      female patients, violent victimization was independently positively associated
      with homelessness, violent offending, a domineering/controlling interpersonal
      style, and negatively associated with being socially inhibited and cold/distant
      (p<0.001; chi2=34.08, d.f.=4, R2=0.53). Property victimization was independently
      associated with theft offending (p<0.001, chi2=26.99, d.f.=5, R2=0.14).
      CONCLUSIONS: Given the high prevalence of victimization in dual diagnosis
      patients and its related problems, preventive interventions should be developed.
      Interventions should target interpersonal skills to decrease vulnerability to
      victimization, address the overlap between victimization and offending and
      incorporate gender-specific elements.

PMID- 29195597
TI  - Organizational Readiness for Change (ORC) test used in the implementation of
      assessment instruments and treatment methods in a Swedish National study.
AB  - : Organizational climate and related factors are associated with outcome and are
      as such of vital interest for healthcare organizations. Organizational Readiness
      for Change (ORC) is the questionnaire used in the present study to assess the
      influence of organizational factors on implementation success. The respondents
      were employed in one of 203 Swedish municipalities within social work and
      psychiatric substance/abuse treatment services. They took part in a nationwide
      implementation project organized by the Swedish Association of Local Authorities
      and Regions (SALAR), commissioned by the Swedish National Board of Health and
      Welfare. AIM: The aims were: (a) to identify classes (clusters) of employees with
      different ORC profiles on the basis of data collected in 2011 and (b) to
      investigate ORC profiles which predicted the use of assessment instruments,
      therapy methods and collaborative activities in 2011 and 2013. DESIGN AND
      RECRUITMENT: The evaluation study applied a naturalistic design with registration
      of outcome at consecutive assessments. The participants were contacted via
      official e-mail addresses in their respective healthcare units and were
      encouraged by their officials to participate on a voluntary basis. STATISTICS:
      Descriptive statistics were obtained using SPSS version 23. A latent profile
      analysis (LPA) using Mplus 7.3 was performed with a robust maximum likelihood
      estimator (MLR) to identify subgroups (clusters) based on the 18 ORC indexes.
      RESULTS: A total of 2402 employees responded to the survey, of whom 1794 (74.7%)
      completed the ORC scores. Descriptive analysis indicated that the respondents
      were a homogenous group of employees, where women (72.0%) formed the majority.
      Cronbach's alpha for the 18 ORC indexes ranged from alpha=0.67 to alpha=0.78. A
      principal component analysis yielded a four-factor solution explaining 62% of the
      variance in total ORC scores. The factors were: motivational readiness
      (alpha=0.64), institutional resources (alpha=0.52), staff attributes
      (alpha=0.76), and organizational climate (alpha=0.74). An LPA analysis of the
      four factors with their three distinct profiles provided the best data fit:
      Profile 3 (n=614), Profile 2 (n=934), and Profile 1 (n=246). Respondents with the
      most favorable ORC scores (Profile 3) used significantly more instruments and
      more treatment methods and had a better collaborating network in 2011 as well as
      in 2013 compared to members in Profile 1, the least successful profile.
      CONCLUSION: In a large sample of social work and healthcare professionals, ORC
      scores reflecting higher institutional resources, staff attributes and
      organizational climate and lower motivational readiness for change were
      associated with a successful implementation of good practice guidelines for the
      care and treatment of substance users in Sweden. Low motivational readiness as a
      construct may indicate satisfaction with the present situation. As ORC proved to
      be an indicator of successful dissemination of evidence-based guidelines into
      routine and specialist healthcare, it can be used to tailor interventions to
      individual employees or services and to improve the dissemination of and
      compliance with guidelines for the treatment of substance users.

PMID- 29195598
TI  - Orphan drug approval for Erdheim-Chester disease.

PMID- 29195599
TI  - A step towards precision medicine in management of fever and neutropenia in
      haematology.

PMID- 29195600
TI  - Serum protein markers of clonal heterogeneity in myeloma.

PMID- 29195601
TI  - Should we treat individuals homozygous for HFE p.Cys282Tyr with ferritin 300-1000
      MUg/L?

PMID- 29195603
TI  - Science, ethics and kindness.

PMID- 29195602
TI  - Reduction of body iron in HFE-related haemochromatosis and moderate iron overload
      (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial.
AB  - BACKGROUND: The iron overload disorder hereditary haemochromatosis is most
      commonly caused by HFE p.Cys282Tyr homozygosity. In the absence of results from
      any randomised trials, current evidence is insufficient to determine whether
      individuals with hereditary haemochromatosis and moderately elevated serum
      ferritin, should undergo iron reduction treatment. This trial aimed to establish
      whether serum ferritin normalisation in this population improved symptoms and
      surrogate biomarkers. METHODS: This study was a multicentre, participant-blinded,
      randomised controlled trial done at three centres in Australia. We enrolled
      people who were homozygous for HFE p.Cys282Tyr, aged between 18 and 70 years,
      with moderately elevated serum ferritin, defined as 300-1000 MUg/L, and raised
      transferrin saturation. Participants were randomly assigned, via a computer
      generated random number, to undergo either iron reduction by erythrocytapheresis
      (treatment group) or sham treatment by plasmapheresis (control group).
      Randomisation was stratified by baseline serum ferritin (<600 MUg/L or >=600
      MUg/L), sex, and study site. Erythrocytapheresis and plasmapheresis were done
      every 3 weeks, the number of procedures and volume of red cells or plasma removed
      determined on the basis of each patient's haemoglobin, haematocrit, and serum
      ferritin concentration, as well their height and weight. In the
      erythrocytapheresis group, the target was to reduce serum ferritin to less than
      300 MUg/L. The number of procedures for the control group was based on the
      initial serum ferritin and prediction of decrease in serum ferritin of
      approximately 120 MUg/L per treatment. The primary outcome was patient-reported
      Modified Fatigue Impact Scale (MFIS) score, measured at baseline and before
      unblinding. Analyses were by intention to treat, including the safety analysis.
      The trial is registered with ClinicalTrials.gov, number NCT01631708, and has been
      completed. FINDINGS: Between Aug 15, 2012, and June 9, 2016, 104 participants
      were randomly assigned to the treatment (n=54) and control (n=50) groups, of whom
      94 completed the study (50 in the treatment group and 44 in the control group).
      Improvement in MFIS score was greater in the treatment group than in the control
      group (mean difference -6.3, 95% CI -11.1 to -1.4, p=0.013). There was a
      significant difference in the cognitive subcomponent (-3.6, -5.9 to -1.3,
      p=0.0030), but not in the physical (-1.90 -4.5 to 0.63, p=0.14) and psychosocial
      (-0.54, -1.2 to 0.11, p=0.10) subcomponents. No serious adverse events occurred
      in either group. One participant in the control group had a vasovagal event and
      17 participants (14 in the treatment group and three in the control group) had
      transient symptoms assessed as related to hypovolaemia. Mild citrate reactions
      were more common in the treatment group (32 events [25%] in 129 procedures)
      compared with the control group (one event [1%] in 93 procedures).
      INTERPRETATION: To our knowledge, this study is the first to objectively assess
      the consequences of iron removal in individuals with hereditary haemochromatosis
      and moderately elevated serum ferritin. Our results suggest that serum ferritin
      normalisation by iron depletion could be of benefit for all individuals with
      hereditary haemochromatosis and elevated serum ferritin levels. FUNDING: National
      Health and Medical Research Council (Australia).

PMID- 29195604
TI  - OPERA, an overview of the organisation of day-case surgery in France.

PMID- 29195605
TI  - Prevention of eye injuries in anaesthesia and intensive care: New expert
      guidelines.

PMID- 29195606
TI  - CAPiTA: The urine antigen detection (SSUAD) was not validated for PCV13
      vaccinated patients.

PMID- 29195607
TI  - Exploratory efficacy endpoints in the Community-Acquired Pneumonia Immunization
      Trial in Adults (CAPiTA).

PMID- 29195608
TI  - Response to publication by Hoshi SL et al.: Cost-effectiveness of varicella
      vaccine against herpes zoster and post-herpetic neuralgia for elderly in Japan.

PMID- 29195609
TI  - Response to Curran and Mrkvan, Letter to the Editor: Response to publication by
      Hoshi SL et al.: Cost-effectiveness of varicella vaccine against herpes zoster
      and post-herpetic neuralgia for elderly in Japan.

PMID- 29195610
TI  - Conflicting results in article describing "HPV-vaccination and risk of chronic
      fatigue syndrome/myalgic encephalomyelitis".

PMID- 29195611
TI  - No conflicting results in the article "HPV vaccination and risk of chronic
      fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study
      from Norway".

PMID- 29195612
TI  - Letter from the Editors.

PMID- 29195613
TI  - Interim FDG-PET Imaging in Lymphoma.
AB  - In the present article, the authors reviewed the rationale of FDG-PET/CT
      performed at an interim time point during therapy (iPET), focusing on the
      transition from standard, anatomical assessment of tumor shrinkage with CT to
      document a chemotherapy response, to the use of functional imaging with PET to
      assess chemosensitivity of the individual tumor. The prognostic or predictive
      role of iPET in different lymphoma subsets has been reviewed, with particular
      emphasis on early and advanced-stage Hodgkin lymphoma, diffuse large B-cell
      lymphoma, peripheral T-cell lymphoma, extranodal natural killer/T-cell lymphoma,
      and primary mediastinal B-cell lymphoma. A large body of evidence exists in most
      lymphoma subtypes stressing the role of iPET for early chemotherapy response
      during first-line chemotherapy treatment, but an increased number of reports have
      recently been published focusing on the role of iPET in relapsed or refractory
      lymphoma to predict treatment outcome. Varying patterns of FDG uptake was
      observed across various lymphoma entities; hence, interpretation of FDG-PET scans
      should be in the context of the tumor architecture and the prevalence of cellular
      population, in particular, neoplastic vs non-neoplastic inflammatory cells
      present in tissue microenvironment. In the second part of the article, the
      authors reviewed the iPET-response adapted clinical trials and the clinical
      benefits of this strategy compared to standard non-PET adapted therapy. In
      particular, the authors extrapolated the reproducibility of FDG-PET image
      interpretation and the feasibility of a timely treatment adaptation based on FDG
      PET results in daily clinical practice. This is essential for the reader, as the
      iPET-adapted strategy has become the standard of care in both early- and advanced
      stage Hodgkin lymphoma, and, in the future, probably this strategy will be
      expanded to primary mediastinal B-cell lymphoma, follicular lymphoma, and
      peripheral T-cell lymphoma.

PMID- 29195614
TI  - Guest Editorial.

PMID- 29195615
TI  - PET/CT for Lymphoma Post-therapy Response Assessment in Hodgkin Lymphoma and
      Diffuse Large B-cell Lymphoma.
AB  - Over the course of many decades, combined chemotherapy and radiotherapy adapted
      to the stage of disease have become the optimal and standard treatment for
      Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma. Besides achieving
      optimized cure rates of the underlying disease, reduction of toxicity has become
      a major goal. Since the introduction of FDG-PET for the staging and restaging of
      patients with lymphoma, a high predictive value of F-18-FDG-PET in response
      assessment has been observed. Several PET-response-guided therapy regimens have
      already been established, and even more PET-adapted study designs are being
      tested in large study groups. PET has a very high negative predictive value
      following chemotherapy, and radiotherapy can be safely omitted in PET-negative
      patients with HL after effective chemotherapy with regimens such as bleomycin,
      etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and
      prednisone in advanced stages. As "state-of-the-art" PET-guided therapy is based
      on the results of large clinical trials, the reliability of end-of-treatment PET
      as a basis for abandoning radiotherapy in early and intermediate HL stages
      remains to be shown. As in HL, the predictive value of FDG-PET after induction
      therapy of diffuse large B-cell lymphoma is higher than that of CT alone so that
      we obtain relevant prognostic information unavailable through anatomical imaging.
      Recent results from trials in aggressive non-HL with a de-escalating strategy
      suggest that radiotherapy may be safely omitted if FDG-PET is negative after
      standard chemoimmunotherapy. Since 2007, FDG-PET at end of treatment is
      integrated into the International Working Group criteria and became the imaging
      tool of choice for response assessment in aggressive lymphoma. Robust and
      reproducible interpretation criteria are being used both in the ongoing clinical
      trials and in daily routine. The recommended five-point scale has become the
      standard in PET response assessment, with the caveat that the consequence of a
      PET scan may be influenced by foregoing and following treatments.

PMID- 29195616
TI  - PET/CT for Lymphoma Post-therapy Response Assessment in Other Lymphomas, Response
      Assessment for Autologous Stem Cell Transplant, and Lymphoma Follow-up.
AB  - FDG-PET/CT is an established first-line diagnostic imaging tool used in the
      staging of most lymphomas and for post-therapy response assessment in Hodgkin
      lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Many of the subtypes of
      lymphoid neoplasms classified by the World Health Organization demonstrate
      significant FDG-avidity or uptake; however, many guidelines and Lugano
      classification do not recommend the use of FDG-PET/CT in assessing response to
      therapy for these non-HL, non-DLBCL subtypes as a first-line diagnostic tool.
      This article reviews the role of FDG-PET/CT in the evaluation of the other most
      common "FDG-avid" lymphomas than HL and DLBCL, the role of FDG-PET/CT before
      autologous stem cell transplant, and for post-treatment follow-up. Follicular
      lymphoma is most commonly FDG-avid with a wide range of uptake that generally
      correlates with the histologic grade, a major determinant of aggressiveness and
      prognosis. FDG-PET/CT is more sensitive and specific than CT for detecting
      residual disease post therapy for both aggressive and indolent follicular
      lymphoma. Post-treatment FDG-PET/CT for follicular lymphoma has significant
      prognostic value, that is, better predicts progression-free and overall survival
      than does conventional post-treatment assessment with CT. FDG-PET/CT is useful in
      the staging of mantle cell lymphoma, a very aggressive, incurable subtype of
      lymphoma; however, data show mixed results on the benefits of FDG-PET/CT over
      conventional CT assessment in post-therapy response evaluation. Peripheral T-cell
      lymphomas, a rare aggressive group of T-cell lymphomas, are often FDG-avid. Post
      therapy FDG-PET/CT results have major prognostic value and therapeutic
      implications in many subtypes of peripheral T-cell lymphomas. Post-treatment FDG
      PET/CT is superior to conventional CT for determining chemosensitivity of
      lymphoma, and therefore is better able to predict which patients will have a
      greater benefit or outcome with autologous stem cell transplant. There are mixed
      data on the value of FDG-PET/CT for surveillance after treatment because of high
      reported false-positive rates and accuracy that depends on the duration or timing
      of surveillance and the subtype of lymphoma.

PMID- 29195617
TI  - PET/CT for Staging; Past, Present, and Future.
AB  - Accurate and reproducible staging is crucial for management of malignant
      lymphomas. Disease stage influences treatment decisions more significantly than
      any other clinical information in most lymphoma subtypes, and contributes with
      important prognostic information on its own or as part of clinical prognostic
      scores. Information derived from medical imaging is the single most important
      determinant of disease stage, and the introduction PET/CT for lymphoma has led to
      substantial changes in the concept as well as practice of lymphoma staging. Over
      time, the most important change in lymphoma staging has been the abandonment of
      extensive pathologic staging intended in the original Ann Arbor classification.
      The 2014 Lugano Classification represents the most recent expert recommendation
      for staging of lymphoma. This revision recognizes the improved diagnostic
      accuracy of PET/CT over stand-alone CT and recommended PET/CT for routine staging
      of all FDG-avid lymphomas. Routine bone marrow biopsies are also discouraged in
      Hodgkin lymphoma as well as in selected cases of diffuse large B-cell lymphoma.
      The scope of this review is to give the reader insight into the history of
      staging, the purpose of lymphoma staging in the context of contemporary treatment
      strategies, and the advantages of PET/CT staging over conventional staging. We
      also discuss the controversies of PET/CT replacing conventional bone marrow
      biopsies in different lymphoma subtypes and summarize recommendations by the
      recent Lugano classification.

PMID- 29195618
TI  - Metabolic Tumor Volume Metrics in Lymphoma.
AB  - Although visual assessment using the Deauville criteria is strongly recommended
      by guidelines for treatment response monitoring in all FDG-avid lymphoma
      histologies, the high rate of false-positives and concerns about interobserver
      variability have motivated the development of quantitative tools to facilitate
      objective measurement of tumor response in both routine and clinical trial
      settings. Imaging studies using functional quantitative measures play a
      significant role in profiling oncologic processes. These quantitative metrics
      allow for objective end points in multicenter clinical trials. However, the
      standardization of imaging procedures including image acquisition parameters,
      reconstruction and analytic measures, and validation of these methods are
      essential to enable an individualized treatment approach. A robust quality
      control program associated with the inclusion of proper scanner calibration,
      cross-calibration with dose calibrators and across other scanners is required for
      accurate quantitative measurements. In this section, we will review the technical
      and methodological considerations related to PET-derived quantitative metrics and
      the relevant published data to emphasize the potential value of these metrics in
      the prediction of patient prognosis in lymphoma.

PMID- 29195619
TI  - PET/CT in Radiation Therapy Planning.
AB  - Radiation therapy (RT) is an important component of the management of lymphoma
      patients. Most lymphomas are metabolically active and accumulate 18F
      fluorodeoxyglucose (FDG). Positron emission tomography with computer tomography
      (PET/CT) imaging using FDG is used routinely in staging and treatment evaluation.
      FDG-PET/CT imaging is now also used routinely for contouring the target for RT,
      and has been shown to change the irradiated volume significantly compared with CT
      imaging alone. Modern advanced imaging techniques with image fusion and motion
      management in combination with modern highly conformal RT techniques have
      increased the precision of RT, and have made it possible to reduce dramatically
      the risks of long-term side effects of treatment while maintaining the high cure
      rates for these diseases.

PMID- 29195620
TI  - PET/CT in Lymphoma: Current Overview and Future Directions.
AB  - Over the past several decades, PET has emerged as critical to accurate staging
      and restaging of lymphomas. Nonetheless, a number of critical issues regarding
      its optimal use remain. Whereas risk-adapted strategies appear to improve the
      outcome of patients with Hodgkin lymphoma, results are less convincing in non
      Hodgkin lymphoma. Assessment of metabolic tumor volume before treatment may
      permit novel induction strategies. New drugs that may induce an immune response
      may result in a false-positive FDG/PET scan, mandating modifications of current
      criteria to consider tumor flare reactions. Application of PET may be improved by
      integration of biomarker studies and a better understanding of the role of the
      microenvironment. Methods to improve the integration of FDG/PET enhance its role
      in the management of patients with lymphoma, leading to improved patient outcome.

PMID- 29195622
TI  - PREFACE ENPE-2017: International conference on Ecotechnologies for Controlling
      Non-point Source Pollution and Protecting Aquatic Ecosystem.

PMID- 29195621
TI  - Giants in Obstetrics and Gynecology Series: A profile of Jennifer Niebyl, MD.

PMID- 29195623
TI  - Clinical utility of self-disclosure for adults who stutter: Apologetic versus
      informative statements.
AB  - PURPOSE: The purpose of the present study was to explore the clinical utility of
      self-disclosure, particularly, whether disclosing in an informative manner would
      result in more positive observer ratings of the speaker who stutters than either
      disclosing in an apologetic manner or choosing not to self-disclose at all.
      METHOD: Observers (N=338) were randomly assigned to view one of six possible
      videos (i.e., adult male informative self-disclosure, adult male apologetic self
      disclosure, adult male no self-disclosure, adult female informative self
      disclosure, adult female apologetic self-disclosure, adult female no self
      disclosure). Observers completed a survey assessing their perceptions of the
      speaker they viewed immediately after watching the video. RESULTS: Results
      suggest that self-disclosing in an informative manner leads to significantly more
      positive observer ratings than choosing not to self-disclose. In contrast, use of
      an apologetic statement, for the most part, does not yield significantly more
      positive ratings than choosing not to self-disclose. CONCLUSION: Clinicians
      should recommend their clients self-disclose in an informative manner to
      facilitate more positive observer perceptions.

PMID- 29195624
TI  - Self-efficacy and quality of life in adults who stutter.
AB  - PURPOSE: Self-efficacy has emerged as a potential predictor of quality of life
      for adults who stutter. Research has focused primarily on the positive
      relationship self-efficacy has to treatment outcomes, but little is known about
      the relationship between self-efficacy and quality of life for adults who
      stutter. The purpose of this mixed- methods study is to determine the predictive
      value of self-efficacy and its relationship to quality of life for adults who
      stutter. METHOD: The Self-Efficacy Scale for Adult Stutterers and the Overall
      Assessment of the Speaker's Experience with Stuttering were administered to 39
      adults who stutter, aged 18- 77. Percentage of syllables stuttered was calculated
      from a conversational speech sample as a measure of stuttered speech frequency.
      Qualitative interviews with semi-structured probes were conducted with 10 adults
      and analyzed using thematic analysis to explore the lived experience of adults
      who stutter. RESULTS: Self-efficacy emerged as a strong positive predictor of
      quality of life for adults living with a stuttered speech disorder. Stuttered
      speech frequency was a moderate negative predictor of self-efficacy. Major
      qualitative themes identified from the interviews with the participants were:
      encumbrance, self-concept, confidence, acceptance, life-long journey, treatment,
      and support. CONCLUSION: Results provide clarity on the predictive value of self
      efficacy and its relationship to quality of life and stuttered speech frequency.
      Findings highlight that the unique life experiences of adults who stutter require
      a multidimensional approach to the assessment and treatment of stuttered speech
      disorders.

PMID- 29195625
TI  - The experience of stuttering among Ultra-Orthodox and Secular/Traditional Jews.
AB  - PURPOSE: This groundbreaking research compares the experience of stuttering among
      adult male People Who Stutter (PWS) from the ultra-Orthodox (UO) Jewish community
      in Israel to those from Secular/Traditional (ST) backgrounds. METHODS:
      Participants were 32 UO and 31 ST PWS, aged 18-67 years. Self-report
      questionnaires utilized: Perceived Stuttering Severity (PSS); Overall Assessment
      of the Speaker's Experience of Stuttering (OASES-A); Students' Life Satisfaction
      Scale (SLSS); Situation Avoidance Behavior Checklist (SABC). Demographic,
      religious, and stuttering information was collected. Groups were compared on
      scales, and correlations between scales and the PSS. RESULTS: Subjective
      stuttering severity ratings were significantly higher among the UO. A significant
      group effect was found for the OASES-A quality of life subscale, but not other
      subscales. Significant positive correlations were found between: 1) PSS and OASES
      A Total Impact; 2) PSS and 3 OASES subscales; and 3) PSS and SABC (indicating
      increased avoidance with increased stuttering severity rating). A significant
      negative correlation was found between the PSS and SLSS, indicating lower life
      satisfaction with higher rates of stuttering severity among the ST.
      Interestingly, when tested by group, significant correlations between the PSS and
      all other study measures were observed only among the ST. CONCLUSION: UO
      participants showed higher subjective stuttering severity ratings, yet less
      impact on quality of life, and no correlation between subjective stuttering and
      other measures of stuttering experience. These novel findings may result from the
      combined protective effect of religiosity and socio-cultural characteristics on
      UO PWS' well-being, despite heightened concern about social consequences of
      stuttering within UO society.

PMID- 29195626
TI  - Effects of emotion on the acoustic parameters in adults who stutter: An
      exploratory study.

PMID- 29195627
TI  - Ethyl pyruvate is renoprotective against ischemia-reperfusion injury under
      hyperglycemia.
AB  - BACKGROUND: Hyperglycemia (HG) is common in cardiovascular surgeries due to
      diabetes, inflammation, and the neuroendocrine stress response. HG aggravates
      renal ischemia-reperfusion (I/R) injury through an increased inflammatory
      response, and blunts the protective effect of various measures. Ethyl pyruvate
      (EP) provides anti-inflammatory effects against I/R injury via inhibition of high
      mobility group box 1 protein (HMGB1) release. This study aimed to determine the
      renoprotective effect of EP against I/R injury under HG. METHODS: Sprague-Dawley
      rats were randomly assigned at random to 8 groups: normoglycemia (NG)-sham, NG
      I/R-control, NG-EP-I/R (pretreatment), NG-I/R-EP (posttreatment), HG-sham, HG-I/R
      control, HG-EP-I/R, and HG-I/R-EP. Renal I/R was induced by 45 minutes of
      ischemia (clamping of renal arteries), followed by 24 hours of reperfusion. EP
      (50 mg/kg) was administered intraperitoneally at 1 h before ischemia
      (pretreatment) or on reperfusion (posttreatment). RESULTS: I/R injury under HG
      significantly aggravated the degree of renal tubular apoptosis and damage
      compared with the NG groups, which could be attenuated by both pretreatment and
      posttreatment of EP. I/R-induced increases in HMGB1 and Toll-like receptors
      (TLRs), activation of NF-kB, and resultant alterations in interleukin-1beta,
      tumor necrosis factor-alpha, proapoptotic Bax, and antiapoptotic Bcl-2 were all
      favorably modulated by EP treatment in both the NG and HG groups compared with
      their corresponding control groups. CONCLUSIONS: Despite aggravation of renal I/R
      injury by HG through amplified inflammation, EP administration showed similar
      suppression of the HMGB1-TLR-NF-kB pathway in the HG and NG groups. EP retained
      anti-inflammatory, antiapoptotic, and renoprotective effects in the HG groups,
      whether administered before ischemia or on reperfusion.

PMID- 29195628
TI  - Family planning decisions for parents of children with a rare genetic condition:
      A scoping review.
AB  - Expansion of newborn screening programmes increases the complexity around
      reproductive choices, both in terms of the increased number of parents faced with
      making reproductive decisions from the earliest days of their affected child's
      life, and the number of conditions for which such decisions have to be made. We
      conducted a scoping review to explore: (i) reproductive decision-making among
      parents of children with recessive genetic conditions; and, (ii) the involvement
      of healthcare services in facilitating and supporting those decisions. Systematic
      search processes involved seven bibliographic databases, citation, and grey
      literature searches. From an initial total of 311 identified articles, seven met
      the inclusion criteria and were included in the review. The extracted data were
      organised around three themes: factors influencing reproductive decisions taken
      by parents, how those factors changed over time, and the involvement of
      healthcare services in supporting and facilitating reproductive decisions. Most
      studies focused on attitudes towards, and uptake of, pre-natal diagnosis (PND)
      and termination. None of the studies considered the wider range of reproductive
      choices facing all parents, including those of children with conditions for whom
      PND and termination is not available or where good health outcomes make these
      options less justifiable. The literature provided little insight into the role of
      healthcare staff in providing family planning support for these parents. There is
      a need to better understand the support parents need in their decision-making,
      and who is best placed to provide that support.

PMID- 29195629
TI  - Decline in contraceptive use in India: A call for action.
AB  - Select estimates of contraceptive use in the 2015-16 National Family Health
      Survey (NFHS is equivalent to the Demographic and Health Survey in India) have
      come under the scrutiny of researchers and policy makers globally. Using four
      waves (1992-93, 1998-99, 2005-06, and 2015-16) of published NFHS reports, this
      article aims to highlight the change in Contraceptive Prevalence Rate (CPR) and
      initiate a discussion to help investigate the reasons for the recent decline of
      CPR.

PMID- 29195630
TI  - Influence of intimate partner violence during pregnancy on fear of childbirth.
AB  - OBJECTIVE: Women are at increased risk of intimate partner violence (IPV) during
      pregnancy. This may impact women's positive anticipation for birth. Negative
      feelings around birth often translate to a fear of childbirth. Our aim was to
      examine the prevalence IPV and whether physical, sexual, psychological IPV during
      pregnancy predicts fear of childbirth among Iranian pregnant women. METHOD: A
      population-based cross sectional study was conducted in North-East Iran. Pregnant
      women (n=174) at least 14weeks gestation attending health centers were selected
      for inclusion through a stratified sampling method. IPV, fear of birth, state and
      trait anxiety and socio-demographic variables were collected using validated
      instruments. To achieve the final models the Bayesian information criterion was
      used. A p value of <0.05 was considered statistically significant. RESULTS:
      Seventy-three percent of women reported experiencing IPV at least once within
      their current pregnancy. Fear of birth was prevalent (61.5%). Logistic regression
      analysis revealed that after adjusting for confounding factors, in nulliparous
      physical IPV significantly predicted fear of birth (adjusted OR=12.15; 95% CI,
      1.33, 110.96) while, in multiparous psychological IPV associated inversely with
      fear of birth (adjusted OR=0.18; 95% CI, 0.04, 0.73). For all participants,
      physical IPV increased the chance of fear of birth, (adjusted OR=2.47; 95% CI,
      1.01, 6.02). CONCLUSION: All pregnant women experiencing physical violence had a
      higher chance of fear of birth. Screening programs for fear of birth and IPV need
      to be implemented in particular for nulliparous women. Providing continuity of
      midwifery care and family therapy may be strategies for early support to reduce
      IPV to pregnant women.

PMID- 29195631
TI  - Preconception health care interventions: A scoping review.
AB  - Pregnancy is often framed as a "window of opportunity" for intervening on a
      variety of health practices such as alcohol and tobacco use. However, there is
      evidence that interventions focusing solely on the time of pregnancy can be too
      narrow and potentially stigmatizing. Indeed, health risks observed in the
      preconception period often continue during pregnancy. Using a scoping review
      methodology, this study consolidates knowledge and information related to current
      preconception and interconception health care interventions published in the
      academic literature. We identified a total of 29 intervention evaluations, and
      summarized these narratively. Findings suggest that there has been some progress
      in intervening on preconception health, with the majority of interventions
      offering assessment or screening followed by brief intervention or counselling.
      Overall, these interventions demonstrated improvements in at least some of the
      outcomes measured. However, further preconception care research and intervention
      design is needed. In particular, the integration of gender transformative
      principles into preconception care is needed, along with further intervention
      design for partners/ men, and more investigation on how best to deliver
      preconception care.

PMID- 29195632
TI  - Parents' involvement in the human papillomavirus vaccination decision for their
      sons.
AB  - OBJECTIVES: Parents are critical to ensure sufficient human papillomavirus (HPV)
      vaccine coverage. No studies to date have examined how mothers and fathers
      perceive their own, their partners' and their sons' involvement in HPV
      vaccination decision-making process. METHODS: An online survey methodology was
      used to collect data from a national sample of Canadian parents (33% fathers, 67%
      mothers, Mage=44) who had a 9-16years old son (n=3117). MAIN OUTCOME MEASURES:
      Parent's perception of their self-involvement, partner-involvement and son's
      involvement in the decision to get their son the HPV vaccine were measured on a
      Likert scale and were classified as 'no involvement', 'moderate involvement' and
      'high involvement'. RESULTS: Mothers and fathers both perceive that they
      themselves and their partners should be highly involved in their son's HPV
      vaccination decision. Son's involvement was reported as moderate and influenced
      by age. Significant gender differences were found for self and partner
      involvement, but the effect sizes were small. CONCLUSION: Mothers and fathers
      both perceive that they themselves and their partners should be significantly
      involved in their son's HPV vaccination decision. A dyad decision-making model
      involving both parents for HPV vaccine decision-making is suggested with a
      stronger recommendation for a triad decision-making model involving both parents
      as well as the child/adolescent. Gender stereotypes of females perceiving
      themselves as the sole decision-maker or fathers not wanting to be involved in
      their children's health decision were not supported.

PMID- 29195633
TI  - Effects of women's autonomy on maternal healthcare utilization in Bangladesh:
      Evidence from a national survey.
AB  - OBJECTIVES: This study aims to construct an index of women's autonomy to analyze
      its effect on maternal healthcare utilization in Bangladesh. Empirical modeling
      of the study used instrumental variable (IV) approach to correct for possible
      endogeneity of women's autonomy variable. METHODS: Data from the Bangladesh
      Demographic and Health Survey (BDHS) 2011 was used for the study. Women's
      autonomy variable was obtained through factor analysis of variables related to
      autonomy in decision making regarding healthcare, financial autonomy and freedom
      of movement. Conditional mixed process (CMP) models were fitted for three
      maternal healthcare indicators: at least four antenatal care (ANC) by trained
      personnel, institutional delivery and postnatal care (PNC) by trained personnel.
      RESULTS: Study sample consisted of 8753 women with 5.5 mean years of schooling.
      Women with no formal education, of Islamic faith, from poorest wealth quintile,
      residing in rural areas and with low autonomy used the maternal healthcare least.
      Marginal effect shows that if women's autonomy score is increased by one unit,
      probability of maternal healthcare utilization will increase by 0.14 for ANC,
      0.14 for institutional delivery, and 0.13 for PNC. CONCLUSIONS: Women's autonomy
      is an important driver of maternal healthcare utilization in Bangladesh. Results
      suggest that women participating in social and economic activities enhances their
      autonomy. Other factors affecting women's autonomy are female literacy,
      educational attainment and households' economic status.

PMID- 29195634
TI  - Choice of contraceptive methods by women's status: Evidence from large-scale
      microdata in Nepal.
AB  - OBJECTIVE: We aimed to investigate how improvement in women's status affects the
      choice of contraceptive methods in Nepal. STUDY DESIGN: We regressed the choice
      of contraceptive methods on women's status and other controlling variables by
      employing large-scale microdata representing over 12,000 married women aged 15-49
      years in Nepal. Years of schooling and literacy were defined as women's status
      variables. We estimated how educational attainment affects the choice of
      contraceptive methods. We also analyzed how fear of their partners affected
      women's choices. RESULTS: Female sterilization was the most common choice among
      the contraceptive methods (25.5% of contraceptive users) in Nepal, followed by
      injections (19.9%). However, our estimation results showed that these options
      change with an improvement in women's status. An additional year of education
      increased the probability that women would choose condoms by 1.2 percentage
      points (95% confidence interval [CI]: 0.7, 1.6) and decreased the probability of
      choosing female sterilization by 1.4 percentage points (95% CI: -1.9, -0.8). For
      the well-educated women, injections and condoms became the first and second
      choices (29.5% and 21.5%), respectively, while female sterilization was the third
      option (17.9%) for contraceptive methods. Women's fear of their partners also
      affected the choice of contraceptive methods. The women who feared their partners
      were 7.0 percentage points more likely to choose female sterilization than
      condoms. CONCLUSION: Improvement in women's status (more education and less fear
      of their partners) changed their contraceptive behaviors by increasing the
      probability of choosing condoms and decreasing the probability of choosing female
      sterilization in Nepal.

PMID- 29195635
TI  - Impact of men's perception on family planning demand and uptake in Nigeria.
AB  - OBJECTIVE: Evidence from the last three Demographic and Health Surveys (DHS) in
      Nigeria shows slow progress in family planning (FP) uptake, despite programmatic
      interventions. While socioeconomic and religious barriers continue to exist,
      psychosocial factors such as negative contraceptive perceptions by male partners
      may influence both spousal FP demand and use. Therefore, this research
      investigates the influence of male partners' contraceptive perceptions on spousal
      FP demand and use. METHODS: We analysed the couple dataset from the 2013 Nigeria
      DHS. RESULTS: One in five men held the perception that contraceptive use is
      women's business whereas two in five men reported that women who use family
      planning may become promiscuous, especially older men, those with no formal
      education, Muslims and residents in rural areas and northern region. Results from
      regression models, controlling for relevant sociodemographic characteristics,
      show that men's perception that contraception is women's business did not
      significantly influence FP demand. However, their fear that women who use family
      planning may become promiscuous was associated with lower odds of FP demand (AOR:
      0.86; 95% CI: 0.76-0.97) and increased the odds of traditional methods use (AOR:
      1.34; 95% CI: 1.01-1.79). CONCLUSION: The findings direct the need to adopt
      targeted approach focusing on couples, and reorient policy and program efforts
      for FP counselling and behavioural changes in men.

PMID- 29195636
TI  - Attitudes of physicians providing family planning services in Egypt about
      recommending intrauterine device for family planning clients.
AB  - OBJECTIVES: To assess the attitudes of physicians providing family planning
      services at the public sector in Egypt about recommending intrauterine device
      (IUD) for family planning clients, and to identify the factors that could affect
      their attitudes. METHODS: A descriptive cross sectional study, in which all the
      physicians providing family planning services in Assiut Governorate were invited
      to complete self-administered questionnaires. The study participants were
      recruited at the family planning sector monthly meetings of the 13 health
      directorates of Assiut Governorate, Upper Egypt. 250 physicians accepted to
      participate in the study. Bivariate and Multivariate regression analyses were
      performed to identify the most important predictors of recommending IUD to family
      planning clients when appropriate. RESULTS: Less than 50% of physicians would
      recommend IUD for clients with proper eligibility criteria; women younger than 20
      years old (49.2%), women with history of ectopic pregnancy (34%), history of
      pelvic inflammatory diseases (40%) or sexually transmitted diseases (18.4%) and
      nulliparous women (22.8%). Receiving family planning formal training within the
      year preceding data collection and working in urban areas were the significant
      predictors of recommending IUD insertion for appropriate clients. CONCLUSION:
      Physicians providing family planning services in Upper Egypt have negative
      attitudes about recommending IUD for family planning clients. Continuous
      education and in-service training about the updated medical eligibility criteria,
      especially for physicians working in rural areas may reduce the unfounded medical
      restrictions for IUD use.

PMID- 29195637
TI  - Professional confidence among Swedish final year midwifery students - A cross
      sectional study.
AB  - OBJECTIVE: Previous international studies have shown that midwifery students do
      not feel confident in many areas where they are supposed to practice
      independently. The knowledge about Swedish midwifery students' confidence is
      fairly under investigated. The purpose of the present study was to explore final
      years' midwifery students' professional confidence in basic midwifery skills
      according to ICM competencies and associated factors. METHODS: A cross-sectional
      survey where all midwifery programs in Sweden were invited to participate. Data
      was collected by a questionnaire that measured midwifery students self-reported
      assessment of confidence against four selected domains of ICM competencies;
      antenatal, intrapartum, postpartum and new-born care. RESULT: The main findings
      of this study showed that Swedish midwifery students were confident in managing
      normal pregnancy, labour and birth. Midwifery students at a school with a medical
      faculty were more confident in handling obstetric emergency situations. Some
      background variables were also associated with confidence. CONCLUSION: This study
      highlighted some midwifery skills that needs further training and reflection.
      More training and developing confidence in complicated and emergency situations
      are needed. There seem to be a need of midwifery education reforms if we believe
      that high levels of confidence at the time of graduation is equal to competent
      and skilled midwives in the future.

PMID- 29195638
TI  - Cause-specific mortality among women of reproductive age: Results from a
      population-based study in an Iranian community.
AB  - PURPOSE OF STUDY: This study was conducted to evaluate the levels, patterns, and
      causes of mortality among women of reproductive age in Northwestern Iran.
      METHODS: Deaths were determined for females resident in West Azerbaijan Province
      of Iran and who died between March 2013 to February 2014 using reproductive age
      mortality survey (RAMOS). Causes of death were ascertained by verbal autopsy (VA)
      and classified based on the International Classification of Diseases, tenth
      revision (ICD-10). Overall and cause-specific mortality rates (MRs) per 100,000
      women with 95% confidence intervals were calculated. RESULTS: A total of 510
      deaths were detected, and VA interviews were conducted with the relatives of the
      deceased Cases; overall MR was 56.59 per 100,000 women (95% CI: 56.49-56.69). The
      highest MR was observed in suicide cases (MR=10.21per 100,000women, 95% CI: 10.15
      10.27), accounting for 18% of all deaths. The most common method of suicide was
      self-inflicted burns (45.6%), followed by deaths due to breast cancer (MR=4.22per
      100,000women, 95% CI: 4.18-4.26), which accounted for the most cancer-related
      mortality. All-cause mortality was associated with age, area of residence,
      marital status, level of education, and ethnic (religious) status relationship
      (P<0.001). CONCLUSION: Suicide, especially self-immolation, was the main cause of
      death among women of reproductive age, and both suicides and breast cancer are
      major public health problems for this group of women.

PMID- 29195639
TI  - Married women's negotiation for safer sexual intercourse in Kenya: Does
      experience of female genital mutilation matter?
AB  - OBJECTIVE: Married women's ability to negotiate for safer sex is important for
      HIV prevention in sub-Saharan Africa, including Kenya. Yet, its relationship to
      female genital mutilation is rarely explored, although female genital mutilation
      has been described as a social norm and marker of womanhood that can control
      women's sexuality. Drawing on the social normative influence theory, this study
      addressed this void in the literature. METHODS: We analysed data from the 2014
      Kenya Demographic and Health Survey using logistic regression. Our sample
      included 8,602 married women. Two indicators of safer sex, namely the ability to
      refuse sex and the ability to ask for condom use, were explored. RESULTS: We
      found that women who had undergone genital mutilation were significantly less
      likely to report that they can refuse sex (OR=0.87; p<.05) and that they can ask
      for condom use during sexual intercourse (OR=0.62; p<.001) than their
      counterparts who had not undergone genital mutilation, while controlling for
      theoretically relevant variables. CONCLUSION: Our findings indicate that the
      experience of female genital mutilation may influence married women's ability to
      negotiate for safer sex through gendered socialization and expectations. Based on
      these findings, several policy implications are suggested. For instance,
      culturally sensitive programmes are needed that target both married women who
      have undergone genital mutilation and their husbands to understand the importance
      of safer sexual practices within marriage.

PMID- 29195640
TI  - "We should be experts, but we're not": Sexual counselling at the antenatal care
      clinic.
AB  - OBJECTIVE: Several studies show that nurses don't meet patients' needs in
      addressing issues around sexuality and sexual health. However, little attention
      has been paid to midwives' views on sexual counselling. This study explores
      midwives' views and experiences on sexual counselling during antenatal care.
      STUDY DESIGN: Semi-structured interviews were conducted with nine midwives at
      seven different antenatal care clinics in southern Sweden. The interviews were
      analysed with qualitative content analysis, and script theory was used as a
      theoretical perspective. RESULTS: The result showed that the midwives considered
      sexuality important but hard to address. Lack of time, knowledge, and
      encouragement from the managerial level and/or lack of counselling tools were
      given as reasons for not bringing it up. In addition, midwives' insecurity turned
      out to be even greater with patients that deviated from the heterosexual norm or
      had another cultural background. CONCLUSION: There are cultural and interpersonal
      scripts in the workplace in which sexuality is not expected to be addressed. As
      long as these are in place, only education will not help to change issues in
      addressing patients' sexuality. Organizational and managerial support along with
      education and opportunities for reflection and dialogue regarding sexual issues
      might help midwives to approach sexuality and change the cultural and
      interpersonal scripts.

PMID- 29195641
TI  - Violence against women - an unacceptable global burden.

PMID- 29195642
TI  - A snapshot on the progress of in vitro toxicology for safety assessment.

PMID- 29195643
TI  - The making of measurement: Editors' introduction.
AB  - This special issue consists of selected papers arising from the interdisciplinary
      conference "The Making of Measurement" held at the University of Cambridge on 23
      24 July 2015. In this introduction, we seek ways to further productive
      interactions among historical, philosophical, and sociological approaches to the
      study of measurement without attempting to lay out a prescriptive program for a
      field of "measurement studies." We ask where science studies has led us, and
      answer: from the function to the making of measurement. We discuss whether there
      is anything privileged or exemplary about physical measurement, and alight upon
      models and metrology, two particular focuses of enquiry that emerge from our
      selection of papers. Those papers with a historical dimension complement an
      already well-developed body of historiography applied to measurement and
      metrology.

PMID- 29195644
TI  - Magnitude, moment, and measurement: The seismic mechanism controversy and its
      resolution.
AB  - This paper examines the history of two related problems concerning earthquakes,
      and the way in which a theoretical advance was involved in their resolution. The
      first problem is the development of a physical, as opposed to empirical, scale
      for measuring the size of earthquakes. The second problem is that of
      understanding what happens at the source of an earthquake. There was a
      controversy about what the proper model for the seismic source mechanism is,
      which was finally resolved through advances in the theory of elastic
      dislocations. These two problems are linked, because the development of a
      physically-based magnitude scale requires an understanding of what goes on at the
      seismic source. I will show how the theoretical advances allowed seismologists to
      re-frame the questions they were trying to answer, so that the data they gathered
      could be brought to bear on the problem of seismic sources in new ways.

PMID- 29195645
TI  - Acidity: Modes of characterization and quantification.
AB  - This paper provides an account of early historical developments in the
      characterization and quantification of acidity, which may be considered
      preliminary steps leading to the measurement of acidity. In this "pre-history" of
      acidity measurement, emphasis is laid on the relative independence of the rich
      empirical knowledge about acids from theories of acidity. Many attempts were made
      to compare and assess the strengths of various acids, based on concrete
      laboratory operations. However, at least until the arrival of the pH measure, the
      quantification attempts failed to produce anything qualifying as a measurement
      scale of a recognizable type. It is doubtful whether even pH qualifies as a true
      measure of acidity, when the full meaning of acidity is taken into account.

PMID- 29195646
TI  - The evaluation of measurement uncertainties and its epistemological
      ramifications.
AB  - The way metrologists conceive of measurement has undergone a major shift in the
      last two decades. This shift can in great part be traced to a change in the
      statistical methods used to deal with the expression of measurement results, and,
      more particularly, with the calculation of measurement uncertainties. Indeed, as
      we show, the incapacity of the frequentist approach to the calculus of
      uncertainty to deal with systematic errors has prompted the replacement of the
      customary frequentist methods by fully Bayesian procedures. The epistemological
      ramifications of the Bayesian approach merge with a deep empiricist mood
      tantamount to an "epistemic turn": measurement results are analysed in terms of
      degrees of belief, and central concepts such as error and accuracy are called
      into question. We challenge the perspective entailed by this epistemic turn: we
      insist on the centrality of the concepts of error and accuracy by underlining the
      intentional character of measurement that is intimately linked to the process of
      correction of experimental data. We further circumvent the difficulties posed by
      the classical analysis of measurement by stressing the social rather than the
      epistemic dimension of measurement activities.

PMID- 29195647
TI  - Calibration: Modelling the measurement process.
AB  - Calibration procedures establish a reliable relation between the final states
      ('indications') of a measurement process and features of the objects being
      measured ('outcomes'). This article analyzes the inferential structure of
      calibration procedures. I show that calibration is a modelling activity, namely
      the activity of constructing, deriving predictions from, and testing theoretical
      and statistical models of a measurement process. Measurement outcomes are
      parameter value ranges that maximize the predictive accuracy and mutual coherence
      of such models, among other desiderata. This model-based view of calibration
      clarifies the source of objectivity of measurement outcomes, the nature of
      measurement accuracy, and the close relationship between measurement and
      prediction. Contrary to commonly held views, I argue that measurement standards
      are not necessary for calibration, although they are useful in maintaining
      coherence across large networks of measurement procedures.

PMID- 29195648
TI  - A structural interpretation of measurement and some related epistemological
      issues.
AB  - Measurement is widely applied because its results are assumed to be more reliable
      than opinions and guesses, but this reliability is sometimes justified in a
      stereotyped way. After a critical analysis of such stereotypes, a structural
      characterization of measurement is proposed, as partly empirical and partly
      theoretical process, by showing that it is in fact the structure of the process
      that guarantees the reliability of its results. On this basis the role and the
      structure of background knowledge in measurement and the justification of the
      conditions of object-relatedness ("objectivity") and subject-independence
      ("intersubjectivity") of measurement are specifically discussed.

PMID- 29195649
TI  - The appeal to robustness in measurement practice.
AB  - This paper distinguishes between two arguments based on measurement robustness
      and defends the epistemic value of robustness for the assessment of measurement
      reliability. I argue that the appeal to measurement robustness in the assessment
      of measurement is based on a different inferential pattern and is not exposed to
      the same objections as the no-coincidence argument which is commonly associated
      with the use of robustness to corroborate individual results. This investigation
      sheds light on the precise meaning of reliability that emerges from measurement
      assessment practice. In addition, by arguing that the measurement assessment
      robustness argument has similar characteristics across the physical, social and
      behavioural sciences, I defend the idea that there is continuity in the notion of
      measurement reliability across sciences.

PMID- 29195650
TI  - Clinical outcome measurement: Models, theory, psychometrics and practice.
AB  - In the last decade much has been made of the role that models play in the
      epistemology of measurement. Specifically, philosophers have been interested in
      the role of models in producing measurement outcomes. This discussion has
      proceeded largely within the context of the physical sciences, with notable
      exceptions considering measurement in economics. However, models also play a
      central role in the methods used to develop instruments that purport to quantify
      psychological phenomena. These methods fall under the umbrella term
      'psychometrics'. In this paper, we focus on Clinical Outcome Assessments (COAs)
      and discuss two measurement theories and their associated models: Classical Test
      Theory (CTT) and Rasch Measurement Theory. We argue that models have an important
      role to play in coordinating theoretical terms with empirical content, but to do
      so they must serve: 1) as a representation of the measurement interaction; and 2)
      in conjunction with a theory of the attribute in which we are interested. We
      conclude that Rasch Measurement Theory is a more promising approach than CTT in
      these regards despite the latter's popularity with health outcomes researchers.

PMID- 29195651
TI  - No actual measurement ... was required: Maxwell and Cavendish's null method for
      the inverse square law of electrostatics.
AB  - In 1877 James Clerk Maxwell and his student Donald MacAlister refined Henry
      Cavendish's 1773 null experiment demonstrating the absence of electricity inside
      a charged conductor. This null result was a mathematical prediction of the
      inverse square law of electrostatics, and both Cavendish and Maxwell took the
      experiment as verifying the law. However, Maxwell had already expressed absolute
      conviction in the law, based on results of Michael Faraday's. So, what was the
      value to him of repeating Cavendish's experiment? After assessing whether the law
      was as secure as he claimed, this paper explores its central importance to the
      electrical programme that Maxwell was pursuing. It traces the historical and
      conceptual re-orderings through which Maxwell established the law by constructing
      a tradition of null tests and asserting the superior accuracy of the method.
      Maxwell drew on his developing 'doctrine of method' to identify Cavendish's
      experiment as a member of a wider class of null methods. By doing so, he appealed
      to the null practices of telegraph engineers, diverted attention from the flawed
      logic of the method, and sought to localise issues around the mapping of numbers
      onto instrumental indications, on the grounds that 'no actual measurement ... was
      required'.

PMID- 29195652
TI  - From artefacts to atoms - A new SI for 2018 to be based on fundamental constants.
AB  - At the 26th General Conference on Weights and Measures (CGPM) in November 2018,
      it is planned to adopt a new definition of the International System of Units, SI,
      based on the fixed numerical values of seven defining constants, broadly the
      fundamental constants of physics. This will be the culmination of more than two
      hundred years of metrology, instantiating for the first time the original ideas
      of the creators of the metric system. The key is the replacement of the present
      definition of the unit of mass, the kilogram artefact of platinum-iridium, by one
      based on a fixed numerical value of the Planck constant. This article outlines
      how this has come about, how it will work, why we need a system of measurement
      that is uniform, accessible world-wide and stable in the long term, and the
      international structures that now exist to achieve it.

PMID- 29195653
TI  - What's nu? A re-examination of Maxwell's 'ratio-of-units' argument, from the
      mechanical theory of the electromagnetic field to 'On the elementary relations
      between electrical measurements'.
AB  - This re-examination of the earliest version of Maxwell's most important argument
      for the electromagnetic theory of light-the equality between the speed of wave
      propagation in the electromagnetic ether and the ratio of electrostatic to
      electromagnetic measures of electrical quantity-establishes unforeseen
      connections between Maxwell's theoretical electrical metrology and his mechanical
      theory of the electromagnetic field. Electrical metrology was not neutral with
      respect to field-theoretic versus action-at-a-distance conceptions of electro
      magnetic interaction. Mutual accommodation between these conceptions was reached
      by Maxwell on the British Association for the Advancement of Science (BAAS)
      Committee on Electrical Standards by exploiting the measurement of the medium
      parameters-electric inductive capacity and magnetic permeability-on an arbitrary
      scale. While he always worked within this constraint in developing the 'ratio-of
      units' argument mathematically, I maintain that Maxwell came to conceive of the
      ratio 'as a velocity' by treating the medium parameters as physical quantities
      that could be measured absolutely, which was only possible via the
      correspondences between electrical and mechanical quantities established in the
      mechanical theory. I thereby correct two closely-related misconceptions of the
      ratio-of-units argument-the counterintuitive but widespread notion that the ratio
      is naturally a speed, and the supposition that Maxwell either inferred or proved
      this from its dimensional formula.

PMID- 29195654
TI  - Hubris to humility: Tonal volume and the fundamentality of psychophysical
      quantities.
AB  - Psychophysics measures the attributes of perceptual experience. The question of
      whether some of these attributes should be interpreted as more fundamental, or
      "real," than others has been answered differently throughout its history. The
      operationism of Stevens and Boring answers "no," reacting to the perceived
      vacuity of earlier debates about fundamentality. The subsequent rise of
      multidimensional scaling (MDS) implicitly answers "yes" in its insistence that
      psychophysical data be represented in spaces of low dimensionality. I argue the
      return of fundamentality follows from a trend toward increasing epistemic
      humility. Operationism exhibited a kind of hubris in the constitutive role it
      assigned to the experimenter's presuppositions that is abandoned by the
      algorithmic methods of MDS. This broad epistemic trend is illustrated by
      following the trajectory of research on a particular candidate attribute: tonal
      volume.

PMID- 29195655
TI  - Twenty years of the Journal of Science and Medicine in Sport.

PMID- 29195656
TI  - Reflecting on 20 years of the Journal of Science and Medicine in Sport.

PMID- 29195657
TI  - Twenty articles for twenty years.

PMID- 29195658
TI  - A Typical Case of Lipoblastoma on the Lower Limb of an Infant.

PMID- 29195659
TI  - Validation of cardiac magnetic resonance tissue tracking in the rapid assessment
      of RV function: a comparative study to echocardiography.
AB  - AIM: To investigate the accuracy of cardiac magnetic resonance (CMR) tissue
      tracking (CMR-TT) and speckle tracking echocardiography (STE) against CMR
      determined right ventricular (RV) ejection fraction (RVEF) and to identify an
      optimal cut-off value for STE and CMR-TT to determine RVEF <45% and compare this
      to other conventional methods for estimating RVEF in dilated cardiomyopathy (DCM)
      patients. MATERIALS AND METHODS: Twenty-nine DCM patients were recruited
      prospectively. CMR and echocardiography were performed within 48 hours and four
      chamber views were used for strain analysis. Contoured CMR short axis images
      provided RVEF. Intraclass correlation coefficient (ICC), bias, levels of
      agreement, and receiver operating characteristic (ROC) curve analyses were
      performed. RESULTS: CMR-TT RV free-wall longitudinal strain (FLS) and STE RV
      global longitudinal strain (GLS) showed the best correlation with RVEF (r=-0.68,
      r=-0.82, p<0.001 respectively). There was moderate correlation between
      echocardiography RV GLS and CMR RV FLS (r=0.64, p<0.001). CMR-TT FLS showed
      excellent intra-observer and interobserver reliability (ICC=0.980; ICC=0.968
      respectively). STE GLS correlated better with RVEF than with peak systolic
      annular velocity (S'; r=0.45), tricuspid annular plane systolic excursion (TAPSE;
      r=0.56), and fractional area change (FAC; r=0.78). CMR-TT RV FLS had better
      correlation with RVEF than CMR TAPSE (r=0.69 versus 0.40). ROC analysis
      demonstrated the optimal cut-off value for CMR-TT RV FLS and STE GLS in detection
      of RVEF <45% was >=-24.4% (area under the curve=0.87, 100% sensitivity, 66.7%
      specificity) and >=-20.9% (area under the curve=0.88, 100% sensitivity, 60%
      specificity) respectively. CONCLUSION: CMR-TT FLS and STE GLS showed potential to
      provide rapid assessment of RV function and had superior correlation with RVEF
      compared to conventional parameters.

PMID- 29195660
TI  - Detection of clinically occult primary tumours in patients with cervical
      metastases of unknown primary tumours: comparison of three-dimensional THRIVE
      MRI, two-dimensional spin-echo MRI, and contrast-enhanced CT.
AB  - AIM: To evaluate and compare the utility of contrast-enhanced three-dimensional
      (3D) T1-weighted high-resolution isotropic volume examination (THRIVE), spin-echo
      (SE) T1-weighted magnetic resonance imaging (MRI), and computed tomography (CT)
      for detecting clinically occult primary tumours in patients with cervical lymph
      node metastases. MATERIALS AND METHODS: Seventy-three consecutive patients with
      tumours that went undetected during endoscopic or physical examinations underwent
      preoperative contrast-enhanced CT and MRI (SE and 3D THRIVE) after gadolinium
      injection. Guided biopsy results served as reference standards. The diagnostic
      performances of the imaging techniques were compared with McNemar's tests.
      RESULTS: Primary tumours were identified in 59 (80.8%) of the 73 patients after
      surgery. Of these, 36 were found in the palatine tonsil, 11 in the base of the
      tongue, seven in the nasopharynx, and five in the pyriform sinus. The sensitivity
      (72.9%) and accuracy (71.2%) of 3D THRIVE for detecting primary tumours were
      higher than were those of SE T1-weighted MRI (49.2% and 53.4%, p<=0.002) or CT
      (36.4% and 46.4%, p<=0.001). The specificities of these techniques did not
      differ. The diagnostic performance of 3D THRIVE (area under the curve
      [AUC]=0.681) for detecting tumours did not differ from that of SE T1-weighted MRI
      or CT (AUC=0.671 and 0.608, p>0.05). CONCLUSION: 3D THRIVE was more sensitive at
      detecting primary tumours than was SE T1-weighted MRI or CT in patients with
      cervical metastases of unknown primary tumours. This sequence may improve biopsy
      and therapeutic planning in these patients.

PMID- 29195661
TI  - A study on the onset of turbulent conditions with supercritical fluid
      chromatography mobile-phases.
AB  - Following a recent publication [1], the topic of turbulent flow in SFC has
      generated both interest and questions. Liquid-like density, coupled with
      significantly low viscosity of CO2-based mobile-phases may result in high
      Reynolds number (Re) - higher than what represents laminar flow conditions,
      reaching the so-called turbulent regions. Although such turbulent flows can form
      only in the connecting tubings, thus not directly affecting the chromatographic
      process, it is important to know under many situations, whether the flow inside
      the tubing is laminar or turbulent. In this report a comprehensive guideline to
      identify the possibilities of turbulent flow conditions is provided through a
      series of charts. Flow properties depend on state conditions (composition,
      pressure and temperature) and also on the tubing material and geometry. Here
      guidelines to detect the onset of turbulent conditions is provided for
      cylindrical stainless-steel tubings of different internal diameters (i.d.) under
      a wide range of SFC mobile-phase conditions.

PMID- 29195662
TI  - Differentiation of modern and ancient varieties of common wheat by quantitative
      capillary electrophoretic profile of phenolic acids.
AB  - Phenolic compounds have received great attention among the health promoting
      phytochemicals in common wheat (Triticum aestivum L.), mainly because of their
      strong antioxidant properties. In the present study a simple Capillary Zone
      Electrophoresis (CZE) method with UV detection was optimized and validated for
      the quantitation of six of the most important phenolic acids in whole grain i.e.,
      sinapic, ferulic, syringic, p-coumaric, vanillic and p-hydroxybenzoic acid. The
      separation was achieved in a running buffer composed of sodium phosphate solution
      (50 mM) in water/methanol 80:20 (v/v) at pH 6.0 and using a fused-silica
      capillary at the temperature of 30  degrees C under application of 27 kV. By
      means of diode array detector, and made possible by the favorable characteristic
      UV spectra, the quantitation of the solutes was carried out at 200, 220 and 300
      nm, in the complex matrices represented by the soluble and bound fractions of
      wheat flours. The validation parameters of the method i.e., linearity,
      sensitivity, precision, accuracy and robustness were in line with those obtained
      by consolidated separation techniques applied for the same purposes (e.g., HPLC
      UV), with a significant advantage in term of analysis time (less than 12 min).
      Ten varieties of soft wheat (five modern Italian and five old Italian genotypes)
      were analysed and the data were subjected to Principal Components Analysis (PCA).
      Interestingly, significant differences of the quantitative phenolic acids profile
      were observed between the modern and the ancient genotypes, with the latter
      showing higher amount of the main represented phenolic acids.

PMID- 29195663
TI  - Forensic age-at-death estimation from the sternum in a black South African
      population.
AB  - Age-at-death estimation is a crucial component of any forensic anthropological
      analysis. Despite a variety of research in this field, uncertainties still exist
      when estimating adult age. The sternum is an under-considered element in terms of
      adult age estimation. Previous research on an Indian population suggested that
      this may be a usable region of the skeleton, although results were ambivalent.
      This study observed the fusion phases of 461 sterna from a black South African
      population in an attempt to match true age of an individual with the different
      phases of synostosis of the manubrio-sternal and the sterno-xiphoidal junctions.
      The results demonstrated that the majority of sterna remain unfused throughout
      adult life, with complete fusion observed both in young (25 year-old) and old
      individuals. Significant differences were identified amongst male and female
      sterna, with males presenting no transitional fusion of the segments, while
      female sterna demonstrated fusion to a lesser extent. Overall, logistic
      regression results demonstrated low accuracies (62.5%) for age estimation even
      when the two sexes were considered separately (male=63.9%; female=61.8%). The
      synostosis of both junctions is hence considered highly variable and deemed
      unreliable for adult age-at-death estimation in the black South African
      population.

PMID- 29195664
TI  - [Actinomycosis revealed by ulceration of the palate and gingiva].
AB  - BACKGROUND: Actinomycosis is a chronic and extensive granulomatous, bacterial
      infection. Revelation by oral ulceration is rare. PATIENTS AND METHODS: A 76-year
      old patient with diabetes was treated with dabrafenib for stage IV melanoma. A
      follow-up visit revealed two ulcerated, infiltrated and hyperalgesic lesions of
      the palate and gingiva. There were no associated signs. The laboratory findings
      were normal. The possibility of squamous cell carcinoma occurring with BRAF
      inhibitors was discussed, despite the rarity of such cases in the literature.
      Histological examination showed an actinomycotic grain. A scan of the facial mass
      showed no osteitis. Antimicrobial therapy was initiated with amoxicillin for four
      months, with a favorable outcome. DISCUSSION: Actinomycetes are Gram-positive
      filamentous saprophytic bacteria of the oral cavity and the gastrointestinal
      tract. They can become pathogenic under the influence of several factors.
      Cervicofacial involvement in the form of a peri-mandibular inflammatory nodule
      with secondary fistulation on the skin or in the mouth is the classic
      presentation. To our knowledge, no cases of opportunistic infection under BRAF
      inhibitors have been described. Only two cases of tuberculosis have been reported
      with sorafenib. The initial presentation led to suspicion of squamous cell
      carcinoma. In our patient, poor oral hygiene and diabetes were the two key
      factors considered. Moreover, this is the first case reported under dabrafenib,
      which does not appear to be a favoring factor. We would stress the importance of
      mucosal examination in patients treated with BRAF inhibitors.

PMID- 29195666
TI  - Mind the gap - Why is implementing research into practice so challenging?

PMID- 29195665
TI  - Wearing of examination gloves and hygiene practice among dermatologists: A
      national survey.
AB  - INTRODUCTION: Touch is essential for dermatologists. Differences in practice,
      such as whether or not to wear examination gloves, may be seen among
      dermatologists. To investigate this approach and its associated factors, we
      conducted a national survey to study hygiene measures and the wearing of gloves
      among dermatologists, e.g. wearing a coat, hand washing between patient visits,
      hand shaking and past history of infectious disease transmitted by patients. The
      context and circumstances in which gloves were worn was studied. RESULTS: Four
      hundred and seventy-four dermatologists responded to the survey (median age: 52
      years). Most dermatologists reported wearing examination gloves as follows:
      always (21%, n=99), occasionally (76%, n=359), never (3%, n=13). Most physicians
      reported wearing a coat (91%, n=419) and routinely washing their hands after
      examination (53%, n=241). A minority of physicians reported shaking hands (36%,
      n=163). A significant number of dermatologists reporting that they wore
      examination gloves were younger and female, and these practitioners also washed
      their hands more frequently. The most common reason cited by dermatologists
      wearing gloves "occasionally" was patient hygiene (71%, n=256) rather than
      infectious skin disease (52%, n=186). This practice was ascribable more to
      concerns by dermatologists about protecting themselves (78%, n=270) rather than
      protecting patients (51%, n=169). Finally, it was felt that wearing gloves
      impaired neither the quality of clinical examination (52%, n=173) nor relations
      with patients (49%, n=160). CONCLUSION: Although wearing gloves is not
      recommended for examining unbroken skin, most of the respondents reported wearing
      examination gloves during their consultations. Wearing of gloves was associated
      with more frequent hygiene measures (hand washing, no handshaking) and was based
      on concern for self-protection.

PMID- 29195667
TI  - Alcohol, smoking and the GI tract.

PMID- 29195668
TI  - Key role of local acetaldehyde in upper GI tract carcinogenesis.
AB  - Ethanol is neither genotoxic nor mutagenic. Its first metabolite acetaldehyde,
      however, is a powerful local carcinogen. Point mutation in ALDH2 gene proves the
      causal relationship between acetaldehyde and upper digestive tract cancer in
      humans. Salivary acetaldehyde concentration and exposure time are the two major
      and quantifiable factors regulating the degree of local acetaldehyde exposure in
      the ideal target organ, oropharynx. Instant microbial acetaldehyde formation from
      alcohol represents >70% of total ethanol associated acetaldehyde exposure in the
      mouth. In the oropharynx and achlorhydric stomach acetaldehyde is not metabolized
      to safe products, instead in the presence of alcohol it accumulates in saliva and
      gastric juice in mutagenic concentrations. A common denominator in alcohol,
      tobacco and food associated upper digestive tract carcinogenesis is acetaldehyde.
      Epidemiological studies on upper GI tract cancer are biased, since they miss
      information on acetaldehyde exposure derived from alcohol and acetaldehyde
      present in 'non-alcoholic' beverages and food.

PMID- 29195669
TI  - Tobacco smoking, alcohol consumption and gastro-oesophageal reflux disease.
AB  - Gastro-oesophageal reflux disease (GORD) develops when reflux of gastric content
      causes troublesome symptoms or complications. The main symptoms are heartburn and
      acid regurgitation and complications include oesophagitis, strictures, Barrett's
      oesophagus and oesophageal adenocarcinoma. In addition to hereditary influence,
      GORD is associated with lifestyle factors, mainly obesity. Tobacco smoking is
      regarded as an aetiological factor of GORD, while alcohol consumption is
      considered a triggering factor of reflux episodes and not a causal factor. Yet,
      both tobacco smoking and alcohol consumption can reduce the lower oesophageal
      sphincter pressure, facilitating reflux. In addition, tobacco smoking reduces the
      production of saliva rich in bicarbonate, which is important for buffering and
      clearance of acid in the oesophagus. Alcohol also has a direct noxious effect on
      the oesophageal mucosa, which predisposes to acidic injury. Tobacco smoking
      cessation reduces the risk of GORD symptoms and avoidance of alcohol is
      encouraged in individuals where alcohol consumption triggers reflux.

PMID- 29195670
TI  - Alcohol, smoking and risk of oesophago-gastric cancer.
AB  - Oesophago-gastric cancers (oesophageal and gastric cancers) are common, highly
      fatal cancers. Oesophageal squamous cell carcinoma (OSCC) and oesophageal
      adenocarcinoma (OAC) are the two main histological subtypes of oesophageal
      cancer. Globally, OSCC remains the most common histological subtype of
      oesophageal cancer, with the highest burden occurring along two geographic belts,
      one from north central China through the central Asian republics to northern
      Iran, and one from eastern to southern Africa. In Western countries, the
      incidence of OAC has increased dramatically over the past 40 years. OAC is now
      the most common subtype of oesophageal cancer in the United States, United
      Kingdom, and Australia. Approximately 90% of gastric cancers are adenocarcinoma,
      with the majority of cases diagnosed in Eastern Asia, Eastern Europe, and some
      Latin American countries. Smoking is an established risk factor for both
      oesophageal (OSCC and OAC) and gastric cancers. Alcohol consumption, however, is
      strongly associated with increased risk of OSCC and probably increases the risk
      of gastric cancer, but is not associated with OAC. Here, we review the current
      epidemiological evidence on associations between alcohol consumption, smoking and
      the risk of developing oesophago-gastric cancer, and emphasize the importance of
      focusing efforts on controlling the worldwide burden of oesophago-gastric cancer
      by reducing alcohol and tobacco use.

PMID- 29195671
TI  - Alcohol, smoking and benign hepato-biliary disease.
AB  - Gallstone disease and pancreatitis are the most frequent benign hepato-biliary
      causes of hospital admissions. Gallstone disease is prevalent, but symptomatic
      disease develops only in about one out of five carriers. Alcohol intake seems to
      protect gallstone formation in cohort studies possibly through effects on bile
      cholesterol metabolism, the enterohepatic circulation, and gallbladder function.
      The impact of smoking on gallstone formation seems minor. Both alcohol intake and
      smoking do not alter the clinical course of gallstone disease carriers.
      Cholecystectomy is the preferred treatment for symptomatic gallstone disease.
      Studies about the impact of alcohol and smoking on the post-cholecystectomy state
      are few and future studies should be performed. Pancreatitis is associated with
      both excessive alcohol intake and smoking in observational studies.
      Interpretation of associations with pancreatitis is hampered by an incomplete
      understanding of underlying mechanisms and by the co-existence of excessive
      alcohol intake and smoking. Smoking cessation and alcohol abstinence is
      recommended in the treatment of pancreatitis, but higher-level evidence is
      needed.

PMID- 29195673
TI  - Alcohol, smoking and the liver disease patient.
AB  - Alcohol is an established risk factor for cirrhosis. Current recommendations for
      a "safe" limit for alcohol consumption are usually set to around 30 g of alcohol
      per day for men and 20 g per day for women, but evidence is mounting that these
      cut-offs might be set too high. Also, inter-individual differences in the hepatic
      sensitivity for alcohol likely play into the risk of development of cirrhosis. In
      patients with concomitant liver diseases, a synergistic effect on fibrosis
      progression and high consumption of alcohol is evident. The role of low to
      moderate consumption is less clear. Alcohol can also lead to a specific
      inflammatory state in the liver, alcoholic hepatitis (AH). Treatment of severe AH
      consists of corticosteroids, which are at best moderately effective, and new
      treatments are needed. Liver transplantation is an option in severe alcoholic
      liver disease, although selection of patients that are at a very low risk of post
      transplantation alcohol consumption is paramount. There is some evidence to
      suggest an increased risk for fibrosis progression and development of
      hepatocellular carcinoma specifically for smoking.

PMID- 29195672
TI  - Tobacco and alcohol as risk factors for pancreatic cancer.
AB  - Pancreatic cancer is projected to become the leading cause of cancer deaths by
      2050. The risk for pancreatic cancer may be reduced by up to 27% by modifying
      lifestyle risk factors, most notably tobacco smoking. Based on analysis of more
      than 2 million unselected individuals from general population, this article
      quantified the risk of pancreatic cancer in relation to lifelong tobacco smoking
      and alcohol consumption status, both alone and in combination. It also provided a
      state-of-the-art review of animal studies on the effect of tobacco smoke and
      alcohol on genetically engineered mouse models of pancreatic precursor lesions,
      as well as the role of immune microenvironment in pancreatic carcinogenesis
      activated by tobacco and alcohol.

PMID- 29195674
TI  - The role of smoking and alcohol behaviour in management of functional
      gastrointestinal disorders.
AB  - Functional gastrointestinal disorders (FGIDs) are common disorders in the
      population. Lifestyle habits have been suspected to influence the presence and
      degree of symptoms, and many studies have examined the role of food components
      and physical activity on the disease development. The role of smoking and alcohol
      intake on FGID has been less thoroughly examined. This systematic literature
      review, of a large amount of studies from different countries around the world
      with different design and application of FGID criteria, shows that smoking seems
      to be associated with a significant 50% increased risk of FD for current compared
      with never smokers. The associations between smoking and other FGIDs are weak, if
      present at all. A moderate alcohol intake is not associated with FGIDs. On the
      other hand, a high alcohol intake may lead to development and aggravation of FGID
      symptoms, especially functional dyspepsia.

PMID- 29195675
TI  - The role of smoking and alcohol behaviour in the management of inflammatory bowel
      disease.
AB  - In the era of increasing use of immunosuppressive and biologic therapy for
      inflammatory bowel disease, environmental influences remain important independent
      risk factors to modify the course of the disease, affect the need for surgery and
      recurrence rates post-surgical resection. The effect of smoking on inflammatory
      bowel disease has been established over the decades, however the exact mechanism
      of how smoking affects remains as area of research. Alcohol is also among the
      socio-environmental factors which has been recognised to cause a flare of
      symptoms in inflammatory bowel disease patients. Nonetheless, the exact relation
      to date is not fully understood, and various paradoxical results from different
      studies are still a point of controversy.

PMID- 29195676
TI  - Alcohol, smoking and the risk of premalignant and malignant colorectal neoplasms.
AB  - Colorectal cancer (CRC) is the third most common cancer worldwide and has a
      complex aetiology consisting of environmental and genetic factors. In this
      review, we evaluate the roles of alcohol and tobacco smoking in colorectal
      neoplasia. Alcohol intake and tobacco smoking are associated with modest, but
      significantly, increased risks of CRC, adenomatous and serrated polyps. There is
      consistent evidence of dose-response relationships for both alcohol and smoking,
      and risk of these neoplasms. Alcohol and smoking appear to be more strongly
      associated with colorectal polyp than CRC development, suggesting roles in the
      initiation of neoplastic growths. These lifestyle factors also seem more strongly
      related to adenomas and sessile serrated lesions than hyperplastic polyps, but
      further confirmation is required. The gastroenterology community has an
      important, yet currently underexploited, role to play addressing the modifiable
      factors associated with CRC and polyps. These behaviours include, but are not
      limited to, alcohol and smoking.

PMID- 29195677
TI  - Do smoking and alcohol behaviours influence GI cancer survival?
AB  - Little is known about the role of alcohol and smoking in GI cancer survival
      compared to GI cancer development. We systematically reviewed the evidence for a
      role of smoking and alcohol in prognosis among GI cancer patients and inform
      whether smoking or alcohol cessation interventions or guidelines for GI cancer
      patients are likely to improve prognosis. A total of 84 relevant studies were
      identified. Continued smokers, particularly heavy smokers, had worse prognosis
      than never smokers in most GI cancers. However, more evidence is needed to
      establish the likely impact of smoking cessation interventions amongst GI cancer
      patients. Heavy alcohol drinkers had worse prognosis in oesophageal squamous cell
      carcinoma and hepatocellular carcinoma patients. Light alcohol consumption was
      not associated with worse prognosis from any GI cancer, though further studies
      are needed. UK guidelines for the general population recommending under 14 units
      (~7 drinks) per week may be sufficient for GI cancer patients, until further
      evidence is available.

PMID- 29195678
TI  - The interaction between smoking, alcohol and the gut microbiome.
AB  - The gastrointestinal microbiome is a complex echosystem that establishes a
      symbiotic, mutually beneficial relation with the host, being rather stable in
      health, but affected by age, drugs, diet, alcohol, and smoking. Alcohol and
      smoking contribute to changes in the stomach and affect H pylori-related
      disorders including the risk of gastric cancer. In the small intestine and in the
      colon alcohol causes depletion of bacteria with anti-inflammatory activity,
      eventually resulting in intestinal damage with "leaky gut". These changes
      contribute to hepatic damage in both alcoholic and non-alcoholic liver disease
      and have been associated with other disorders. Lactobacillus GG and A.
      muciniphila exert a protective effect in this setting. Smoking leads to
      modifications of the gut microbiome linked with a protective effect toward
      ulcerative colitis and deleterious for Crohn's disease. The exact cause-effect
      relation between alcohol and smoking and changes of the gastrointestinal
      microbiome needs further exploration with high throughput methodologies, and
      controlled studies are necessary to define the role of microbiome modulation on
      the immune response and systemic activation of pro-inflammatory pathways.

PMID- 29195679
TI  - Impact of alcohol & smoking on the surgical management of gastrointestinal
      patients.
AB  - Alcohol and smoking are repeatedly described as modifiable risk factors in
      clinical studies across all surgical specialities. These lifestyle choices impart
      a sub-optimal physiology via multiple processes and play an important role in the
      surgical management of the gastrointestinal patient. Cessation is imperative to
      optimise the patient's fitness for surgery with surgery itself being a prime
      opportunity for sustained cessation. A consistent, planned and integrated
      management involving surgical, anaesthetic, medical, and primary care facets will
      aid in successful cessation and perioperative care. This review highlights the
      pathological processes which contribute to perioperative complications and
      details the current practices to detect, predict and appropriately manage the
      perioperative gastrointestinal patient who smokes and consumes alcohol.

PMID- 29195680
TI  - Communication of alcohol and smoking lifestyle advice to the gastroenterological
      patient.
AB  - Effective communication between healthcare staff and patients is central to
      development of the patient-professional relationship. Many barriers influence
      this communication, often resulting in patients' lack of understanding and
      retention of information, particularly affecting advice regarding lifestyle
      habits, such as alcohol consumption and smoking. Alcohol and smoking misuse are
      potentially modifiable risk factors known to adversely affect a variety of
      gastroenterological conditions and improvements in communication with patients
      regarding this is an important management component. This review discusses the
      clinical impact of these factors and how healthcare professionals can improve
      communication. We discuss how enhancing verbal communication skills through
      medical training leads to greater outcomes in patient satisfaction and adherence
      to treatment and advice. In addition, with the rapid digitalisation of society,
      platforms such as social media and smartphone applications may be considered as
      adjuncts to traditional forms of communication.

PMID- 29195681
TI  - Compression sonography for non-invasive measurement of lower leg compartment
      pressure in an animal model.
AB  - INTRODUCTION: Compression ultrasound is a non-invasive technique allowing for
      qualitative visualization and quantitative measurements of mechanical tissue
      properties. In acute compartment syndrome (ACS), cadaver studies have proven that
      the intra-compartmental pressure (ICP) measured by compression sonography
      correlates with the ICP measured invasively. This study aimed to evaluate
      compression sonography for compartment pressure measurements in an animal model.
      MATERIAL AND METHODS: The pressure in the anterior tibial compartment of 6
      domestic pig legs was increased from baseline to 40mmHg in 5mmHg steps. Using
      compression sonography, the compartment diameter was measured without external
      pressure and during manual application of five levels of external pressure. The
      elasticity ratio (ER) was computed as the ratio of the compartment diameter with
      and without external pressure. At 40mmHg of external pressure the ERs at
      different ICP levels were compared using repeated ANOVA measurements. Post-hoc
      comparisons evaluated the lowest detectable ICP fulfilling the definition of ACS
      (ICP>=30mmHg) by starting from each pressure below 30mmHg (baseline, 20mmHg and
      25mmHg, respectively). Receiver operator characteristic analyses defined ER
      limits with appropriate sensitivity and specificity to detect ACS. RESULTS: The
      ER increased from 79.0% at baseline ICP to 89.3% at 40mmHg ICP. The ER at
      baseline and at 20mmHg ICP significantly differed from the ER at 30mmHg ICP
      (p=0.007 and 0.002, respectively); the ER at 25mmHg ICP significantly differed
      from the ER at 40mmHg ICP (p=0.001). An ER less than 87.1% had a sensitivity of
      94.4% and a specificity of 88.9% to proper diagnosis of ACS. CONCLUSION:
      Compression sonography might offer a non-invasive technique to guide treatment in
      cases of uncertain acute compartment syndrome. Further studies are needed to
      collect elasticity ratio data in humans and to clinically validate compression
      sonography for compartment pressure measurements.

PMID- 29195682
TI  - Development of a heat vulnerability index for New York State.
AB  - OBJECTIVES: The frequency and intensity of extreme heat events are increasing in
      New York State (NYS) and have been linked with increased heat-related morbidity
      and mortality. But these effects are not uniform across the state and can vary
      across large regions due to regional sociodemographic and environmental factors
      which impact an individual's response or adaptive capacity to heat and in turn
      contribute to vulnerability among certain populations. We developed a heat
      vulnerability index (HVI) to identify heat-vulnerable populations and regions in
      NYS. STUDY DESIGN: Census tract level environmental and sociodemographic heat
      vulnerability variables were used to develop the HVI to identify heat-vulnerable
      populations and areas. METHODS: Variables were identified from a comprehensive
      literature review and climate-health research in NYS. We obtained data from 2010
      US Census Bureau and 2011 National Land Cover Database. We used principal
      component analysis to reduce correlated variables to fewer uncorrelated
      components, and then calculated the cumulative HVI for each census tract by
      summing up the scores across the components. The HVI was then mapped across NYS
      (excluding New York City) to display spatial vulnerability. The prevalence rates
      of heat stress were compared across HVI score categories. RESULTS: Thirteen
      variables were reduced to four meaningful components representing 1)
      social/language vulnerability; 2) socioeconomic vulnerability; 3)
      environmental/urban vulnerability; and 4) elderly/ social isolation.
      Vulnerability to heat varied spatially in NYS with the HVI showing that
      metropolitan areas were most vulnerable, with language barriers and socioeconomic
      disadvantage contributing to the most vulnerability. Reliability of the HVI was
      supported by preliminary results where higher rates of heat stress were
      collocated in the regions with the highest HVI. CONCLUSIONS: The NYS HVI showed
      spatial variability in heat vulnerability across the state. Mapping the HVI
      allows quick identification of regions in NYS that could benefit from targeted
      interventions. The HVI will be used as a planning tool to help allocate
      appropriate adaptation measures like cooling centers and issue heat alerts to
      mitigate effects of heat in vulnerable areas.

PMID- 29195683
TI  - Re: Letter to the Editor in response to 'The effect of smoking on the risk of
      primary open-angle glaucoma: an updated meta-analysis of six observational
      studies'.

PMID- 29195684
TI  - Mice lacking interleukin-18 gene display behavioral changes in animal models of
      psychiatric disorders: Possible involvement of immunological mechanisms.
AB  - Preclinical and clinical evidence suggests pro-inflammatory cytokines might play
      an important role in the neurobiology of schizophrenia and stress-related
      psychiatric disorders. Interleukin-18 (IL-18) is a member of the IL-1 family of
      cytokines and it is widely expressed in brain regions involved in emotional
      regulation. Since IL-18 involvement in the neurobiology of mental illnesses,
      including schizophrenia, remains unknown, this work aimed at investigating the
      behavior of IL-18 null mice (KO) in different preclinical models: 1. the prepulse
      inhibition test (PPI), which provides an operational measure of sensorimotor
      gating and schizophrenic-like phenotypes; 2. amphetamine-induced hyperlocomotion,
      a model predictive of antipsychotic activity; 3. resident-intruder test, a model
      predictive of aggressive behavior. Furthermore, the animals were submitted to
      models used to assess depressive- and anxiety-like behavior. IL-18KO mice showed
      impaired baseline PPI response, which was attenuated by d-amphetamine at a dose
      that did not modify PPI response in wild-type (WT) mice, suggesting a
      hypodopaminergic prefrontal cortex function in those mice. d-Amphetamine,
      however, induced hyperlocomotion in IL-18KO mice compared to their WT
      counterparts, suggesting hyperdopaminergic activity in the midbrain. Moreover, IL
      18KO mice presented increased basal levels of IL-1beta levels in the hippocampus
      and TNF-alpha in the prefrontal cortex, suggesting an overcompensation of IL-18
      absence by increased levels of other proinflammatory cytokines. Although no
      alteration was observed in the forced swimming or in the elevated plus maze tests
      in naive IL-18KO mice, these mice presented anxiogenic-like behavior after
      exposure to repeated forced swimming stress. In conclusion, deletion of the IL-18
      gene resembled features similar to symptoms observed in schizophrenia (positive
      and cognitive symptoms, aggressive behavior), in addition to increased
      susceptibility to stress. The IL-18KO model, therefore, could provide new
      insights into how changes in brain immunological homeostasis induce behavioral
      changes related to psychiatric disorders, such as schizophrenia.

PMID- 29195685
TI  - Corrigendum to "Tectonics of a K+ channel: The importance of the N-terminus for
      channel gating" [Biochim. Biophys. Acta 1848 (12) (2015) 3197-3204].

PMID- 29195686
TI  - Role of Bile Acids in Metabolic Control.
AB  - Bile acids are endocrine molecules that in addition to facilitating the
      absorption of fat-soluble nutrients regulate numerous metabolic processes,
      including glucose, lipid, and energy homeostasis. The signaling actions of bile
      acids are mediated through specific bile-acid-activated nuclear and membrane
      bound receptors. These receptors are not only expressed by tissues within the
      enterohepatic circulation such as the liver and the intestine, but also in other
      organs where bile acids mediate their systemic actions. In this review, we
      discuss bile acid signaling and the interplay with the gut microbiota in the
      pathophysiology of obesity, type 2 diabetes, and non-alcoholic fatty liver
      disease, and the role of surgical and pharmacological interventions on bile acid
      profiles and metabolism.

PMID- 29195687
TI  - Mobilising experience from Ebola to address plague in Madagascar and future
      epidemics.

PMID- 29195688
TI  - The global fight against malaria is at crossroads.

PMID- 29195689
TI  - [Primary care and detection of colorectal cancer].

PMID- 29195690
TI  - Completed FDA feasibility trial of surgically placed temporary diaphragm pacing
      electrodes: A promising option to prevent and treat respiratory failure.
AB  - BACKGROUND: Etiologies contributing to failure to wean from mechanical
      ventilation (MV) are multiple, resulting in morbid and costly outcomes. Diaphragm
      pacing (DP) is used in spinal cord injury to replace MV. Temporary DP could be
      utilized in acute respiratory failure to reduce MV. METHODS: A prospective FDA
      feasibility trial evaluated temporary DP electrodes implanted in each hemi
      diaphragm during a subject's primary procedure. Objectives included: ability to
      provide ventilation, stability analysis with diaphragm electromyography, and
      adverse event monitoring. RESULTS: Twelve patients underwent successful
      implantation via median sternotomy, laparoscopy or laparotomy. Electrode
      stimulation exceeded ideal tidal volumes by an average of 37% (0%-95%) confirming
      ability to prevent atrophy. Daily electromyography confirmed stability of
      placement and was useful in evaluating hypoventilation. There were no
      complications and all 48 study electrodes remained intact until complete removal.
      CONCLUSION: This trial demonstrates ease of placement, removal, functionality and
      safety of temporary DP electrodes which therapeutically decreases diaphragm
      atrophy.

PMID- 29195691
TI  - Endoscopic and histopathological analysis of incidental focal colorectal 18 F
      fluorodeoxyglucose uptake in PET/CT scan: Colonoscopic evaluation is warranted.
AB  - BACKGROUND: Unexpected focal colorectal 18 F-fluorodeoxyglucose uptake has become
      a common clinical dilemma. The aim of this study was to identify the clinical
      significance of incidentally detected colorectal lesions on PET/CT scans by
      comparing positive PET/CT findings with endoscopic and histopathological
      analysis. METHODS: A retrospective analysis of a colonoscopy database was
      reviewed. All patients that underwent colonoscopy secondary to focal incidental
      uptake on PET/CT were evaluated. PET/CT findings were correlated with endoscopic
      and histopathological results. RESULTS: 84 patients underwent colonoscopy
      secondary to incidental focal colorectal uptake on PET/CT. A total of 63 patients
      had an endoscopic and histological confirmation of the area of abnormality, for a
      positive predictive value of 75%. Newly diagnosed colorectal carcinoma was
      discovered in 13 patients (15.4%) and forty-four patients (52.3%) were discovered
      to have a premalignant lesion. CONCLUSION: Incidental focal colorectal uptake of
      18 F-fluorodeoxyglucose is associated with a substantial risk of underlying
      neoplastic colorectal lesions. Early identification of these lesions may alter
      patient management and treatment plans.

PMID- 29195692
TI  - Evaluation of Medical Students' Perception of an Ophthalmology Career.

PMID- 29195693
TI  - Why is genetics education so important?

PMID- 29195694
TI  - Citation for the 2016 Down Surgical Prize - Michael Thomas Simpson.

PMID- 29195696
TI  - Insufficient evidence about benefits of socket preservation after tooth
      extraction in outcomes important to patients.

PMID- 29195695
TI  - The diagnosis and management of morbidly adherent placenta.
AB  - The incidence of morbidly adherent placenta (MAP) has risen 13-fold since the
      early 1900s and is directly correlated with the rising rate of cesarean delivery.
      It is important for clinicians to screen all pregnancies for MAP at the time of
      routine second-trimester ultrasonography. In addition, patients with risk factors
      (e.g., multiple prior cesarean deliveries) should undergo targeted screening for
      MAP. Optimal maternal and fetal outcomes for these high-risk pregnancies result
      from accurate prenatal diagnosis and comprehensive multidisciplinary preparation
      and delivery between 34 and 36 weeks of gestation. There continue to be large
      knowledge gaps with respect to the optimal management of this condition
      especially around diagnosis, obstetric care, timing of delivery, and surgical
      management. Accordingly, most recommendations are based on expert opinion rather
      than on high-quality evidence. Prospective clinical trials are needed to address
      knowledge gaps and to continue to improve outcomes.

PMID- 29195697
TI  - Uncertainty about marginal adaptation of computer-aided design and computer-aided
      manufacturing-fabricated fixed dental prostheses and whether it compares with
      other techniques or depends on restorative material.

PMID- 29195698
TI  - Local anesthetic administered with a pressure syringe system probably results in
      less successful and insufficient anesthesia than an inferior alveolar nerve block
      in patients undergoing mandibular posterior tooth extractions.

PMID- 29195699
TI  - There seem to be no differences in enamel wear among natural teeth opposing
      monolithic zirconia crowns, porcelain fused-to-metal crowns, and other natural
      teeth.

PMID- 29195700
TI  - Effectiveness of a clinical knowledge support system for reducing diagnostic
      errors in outpatient care in Japan: A retrospective study.
AB  - Clinical evidence has indicated the effectiveness of computer-based systems for
      preventing and reducing diagnostic errors. Our study aimed to evaluate the
      effectiveness of UpToDate, a computer-based clinical knowledge management system,
      for reducing diagnostic errors. We retrospectively identified 100 patients who
      visited an outpatient department in a community-based hospital from July 2014 to
      June 2015. Fifty patients (exposure group) were seen by UpToDate-equipped
      physicians and another 50 (control group) were seen by UpToDate-unequipped
      physicians. We extracted data on patient sex, age, primary diagnosis, and case
      difficulty that could potentially affect diagnostic outcomes. We compared the two
      groups regarding diagnostic error rate and performed logistic regression analysis
      to analyze the concurrent effects of various factors affecting diagnostic error.
      The diagnostic error rate was 2% in the exposure group, while the error rate was
      24% in the control group. Multivariate logistic regression analysis showed that
      error rate reduction was significantly associated with exposure to UpToDate with
      an odds ratio of 15.21 (95% CI 1.86-124.36). Our results demonstrated the
      effectiveness of UpToDate for the prevention and reduction of diagnostic error.

PMID- 29195701
TI  - Adequacy of UTAUT in clinician adoption of health information systems in
      developing countries: The case of Cameroon.
AB  - PURPOSE: Despite the great potential Health Information Systems (HIS) have in
      improving the quality of healthcare delivery services, very few studies have been
      carried out on the adoption of such systems in developing countries. This article
      is concerned with investigating the adequacy of UTAUT1 in determining factors
      that influence the adoption of HIS by clinicians in developing countries, based
      on the case of Cameroon. METHODS: A paper-based questionnaire was distributed to
      clinicians in 4 out of 7 major public hospitals in Cameroon. A modified UTAUT was
      tested using structural equation modeling (SEM) method to identify the
      determinants of clinicians' intention to use HIS. Self-efficacy and cost
      effectiveness were determinants used to extend the original UTAUT. RESULTS: 228
      out of 286 questionnaires were validated for this study. The original UTAUT
      performed poorly, explaining 12% of the variance in clinicians' intention to use
      HIS. Age was the only significant moderating factor, improving the model to 46%.
      Self-efficacy and cost effectiveness has no direct significant effect on HIS
      adoption in the context of this study. CONCLUSIONS: The original UTAUT is not
      adequate in identifying factors that influence the adoption of HIS by clinicians
      in developing countries. Simplifying the model by using age as the only
      moderating factor significantly increases the model's ability to predict HIS
      adoption in this context. Thus, the younger clinicians are more likely and ready
      to adopt HIS than the older ones. Context-specific should also be used to
      increase the explanatory power of UTAUT in any given context.

PMID- 29195702
TI  - Site readiness assessment preceding the implementation of a HIV care and
      treatment electronic medical record system in Kenya.
AB  - INTRODUCTION: Electronic medical record (EMR) systems can yield many benefit;
      however, facilities need to meet certain requirements before they are able to
      successfully implement an EMR. We evaluated the feasibility and utility of
      conducting EMR readiness assessments (ERAs) to assess readiness of public
      facilities in Kenya for deployment of an EMR. METHOD: I-TECH supported the
      Ministry of Health to deploy KenyaEMR, an HIV/AIDS care and treatment EMR
      developed using the OpenMRS platform, at over 300 healthcare facilities in Kenya.
      The ERA tool was designed to assess site readiness for KenyaEMR deployment. The
      assessments measured health facility internal environment in terms of available
      resources, security, technical infrastructure, and leadership buy-in and support
      from MOH and stakeholders for EMR implementation. RESULTS: From September 2012 to
      September 2014, a total of 381facilities received at least one ERA. Of these,
      343facilities were rated as highly or moderately prepared to adopt an EMR system
      and proceeded to EMR deployment. 61% of these sites were set up to implement
      KenyaEMR at point of care, while 39% were set up to implement KenyaEMR for
      retrospective data entry. Across 38facilities not implemented with an EMR, common
      reasons that prevented the implementation were lack of reliable power, security
      issues such as lack of grills on the windows and un-lockable doors, and existence
      of another EMR system at the site. CONCLUSIONS: ERAs conducted in a single day
      site visit were feasible and were instrumental in determining facilities' EMR
      implementation decision. Performing ERAs stimulated engagement of facility-level
      personnel to cultivate a fertile environment for EMR adoption and ownership. The
      assessments further assisted in resource mobilization, remediation of barriers to
      deployment, and increased buy-in from Ministry of Health leadership to support
      EMR implementation work.

PMID- 29195703
TI  - Supervised learning methods for pathological arterial pulse wave differentiation:
      A SVM and neural networks approach.
AB  - OBJECTIVE: The main goal of this study was to develop an automatic method based
      on supervised learning methods, able to distinguish healthy from pathologic
      arterial pulse wave (APW), and those two from noisy waveforms (non-relevant
      segments of the signal), from the data acquired during a clinical examination
      with a novel optical system. MATERIALS AND METHODS: The APW dataset analysed was
      composed by signals acquired in a clinical environment from a total of 213
      subjects, including healthy volunteers and non-healthy patients. The signals were
      parameterised by means of 39pulse features: morphologic, time domain statistics,
      cross-correlation features, wavelet features. Multiclass Support Vector Machine
      Recursive Feature Elimination (SVM RFE) method was used to select the most
      relevant features. A comparative study was performed in order to evaluate the
      performance of the two classifiers: Support Vector Machine (SVM) and Artificial
      Neural Network (ANN). RESULTS AND DISCUSSION: SVM achieved a statistically
      significant better performance for this problem with an average accuracy of
      0.9917+/-0.0024 and a F-Measure of 0.9925+/-0.0019, in comparison with ANN, which
      reached the values of 0.9847+/-0.0032 and 0.9852+/-0.0031 for Accuracy and F
      Measure, respectively. A significant difference was observed between the
      performances obtained with SVM classifier using a different number of features
      from the original set available. CONCLUSION: The comparison between SVM and NN
      allowed reassert the higher performance of SVM. The results obtained in this
      study showed the potential of the proposed method to differentiate those three
      important signal outcomes (healthy, pathologic and noise) and to reduce bias
      associated with clinical diagnosis of cardiovascular disease using APW.

PMID- 29195704
TI  - Stakeholder influence in public sector information systems strategy
      implementation-The case of public hospitals in South Africa.
AB  - Recent literature on organisational strategy has called for greater emphasis on
      individuals (stakeholders) and what they do in the process of strategizing.
      Public sector organisations have to engage with an array of heterogeneous
      stakeholders in fulfilling their mandate. The public health sector in particular
      needs to engage with a diversity of stakeholders at local, regional and national
      levels when strategising. The purpose of this study is to investigate the
      influence of stakeholder relations on the implementation of Information Systems
      (IS) strategy in public hospitals in South Africa. An interpretive approach using
      two provinces was employed. The Activity Analysis and Development (ActAD)
      framework, an enhanced form of activity theory, was used as the theoretical
      framework. Data was collected using semi-structured interviews, meetings,
      documents analysis, physical artefacts and observation. The collected data was
      analysed using thematic analysis. Findings reveal that IS strategy implementation
      in public hospitals involves a large and complex network of stakeholder groups at
      different levels, and over different time periods. These stakeholder groups act
      in accordance with formal and informal roles, rules and modalities. Various
      contextual conditions together with the actions of, and interactions between
      stakeholder groups give rise to the situationality of stakeholder relations
      dynamics and strategy implementation. The multiple actions and interactions over
      time lead to the realisation of some aspects of the IS strategy in public
      hospitals. Given the complexity and dynamism of the context there are also
      certain unplanned implementations as well. These relationships are captured in a
      Stakeholder Relations Influence (SRI) framework. The SRI framework can be
      assistive in the assessment and mapping of stakeholders and stakeholder
      relations, and the assessment of the implications of these relations for
      effective IS strategy implementation in public hospitals. The framework can also
      provide the basis for the development of appropriate corrective measures in the
      implementation of strategies and policies in public institutions such as public
      hospitals.

PMID- 29195705
TI  - Schedule-based metrics for the evaluation of clinic performance and potential
      recovery of cancelled appointments.
AB  - BACKGROUND: Assessment of outpatient clinic performance is important to optimize
      patient access. Metrics based on schedule data may assist with assessment of
      operational efficiency and recovering cancelled appointments. OBJECTIVES: To
      define schedule-based characteristics of clinic operations and to evaluate
      potential for recovery of cancelled appointments. METHODS: Sixty-seven weekly
      cardiology clinics from a single provider over 18 months at an academic medical
      center were analyzed. Parameters included clinic slots eligible to have patients
      scheduled (available), slots occupied by appointments (scheduled), and slots for
      which patients attended the associated visit (appeared). Rates of usage
      (scheduled/available), appearance (appeared/scheduled), and utilization
      (appeared/available=usage rate*appearance rate) were calculated. Surplus slots
      were defined as the difference between available slots and slots occupied by
      patients that appeared. Cancellation lag-time was defined as the interval between
      a cancellation and the appointment time. If a patient did not notify the clinic
      regarding a non-appearance, cancellation lag-time was set to zero. To quantify
      the impact of a change in clinic operations on efficiency, these metrics were
      used to evaluate a different cardiologist's clinic before and after its physical
      location moved. RESULTS: For approximately 900 patient visits, usage and
      appearance rates were~80%, yielding a utilization rate of ~2/3. On average, there
      were nearly 8 surplus slots per clinic. Approximately 30% of cancellation lag
      times had positive values and nearly half of positive cancellation lag-times were
      >3h, indicating potential for recovery of those appointments. The intervention
      analysis showed that usage rate decreased and surplus slots per clinic increased
      significantly after a change in clinic location. CONCLUSIONS: Schedule-based
      analysis provides a framework to assess changes to clinic operations, identify
      mechanisms underlying inefficiency, and suggest solutions for improving clinic
      performance (i.e. more schedulers in response to low usage rates). Cancellation
      lag-time analysis suggests recovering a portion of same-day cancellations is
      plausible.

PMID- 29195706
TI  - Longitudinal study of user experiences of a CPOE system in a pediatric hospital.
AB  - OBJECTIVE: To explore the views of nurses and doctors during the early stages of
      implementation of a computerized provider order entry (CPOE) system in a
      pediatric hospital and to examine changes in perceptions and reported behaviors
      as use of the CPOE system became routine. METHODS: Semi-structured interviews
      were undertaken at four time points following CPOE implementation: during week
      one, week three, week six and then six months following implementation. In total,
      122 users were interviewed. Interviews were audio-recorded and transcribed
      verbatim. Emergent themes were mapped to the Extended Technology Acceptance Model
      (e-TAM). RESULTS: Initial perceptions were driven by unfamiliarity with the
      system. As users became more proficient and efficient in using the CPOE system,
      additional safety benefits become apparent. However, accompanying increased
      reports of benefits were reports of usability problems and new types of errors
      arising from CPOE use. Reports of workarounds appeared for the first time at 6
      month interviews. These workarounds were adopted to allow routine work to
      continue and to attenuate some of the perceived negative consequences of CPOE,
      including delayed medications and reduced patient interaction. CONCLUSION: This
      study is one of the first to examine changes in perceptions of CPOE at multiple
      points, demonstrating the trajectory of changes in views over time. It provides
      new information about the time point at which workarounds begin to be embedded in
      practice and are potentially most receptive to identification and remediation. It
      suggests an adaptive implementation and support program would be beneficial, as
      reported difficulties and concerns change during the first six months of use.

PMID- 29195707
TI  - iCBLS: An interactive case-based learning system for medical education.
AB  - Medical students should be able to actively apply clinical reasoning skills to
      further their interpretative, diagnostic, and treatment skills in a non-obtrusive
      and scalable way. Case-Based Learning (CBL) approach has been receiving attention
      in medical education as it is a student-centered teaching methodology that
      exposes students to real-world scenarios that need to be solved using their
      reasoning skills and existing theoretical knowledge. In this paper, we propose an
      interactive CBL System, called iCBLS, which supports the development of
      collaborative clinical reasoning skills for medical students in an online
      environment. The iCBLS consists of three modules: (i) system administration (SA),
      (ii) clinical case creation (CCC) with an innovative semi-automatic approach, and
      (iii) case formulation (CF) through intervention of medical students' and
      teachers' knowledge. Two evaluations under the umbrella of the
      context/input/process/product (CIPP) model have been performed with a Glycemia
      study. The first focused on the system satisfaction, evaluated by 54 students.
      The latter aimed to evaluate the system effectiveness, simulated by 155 students.
      The results show a high success rate of 70% for students' interaction, 76.4% for
      group learning, 72.8% for solo learning, and 74.6% for improved clinical skills.

PMID- 29195708
TI  - A new computationally efficient algorithm for record linkage with field
      dependency and missing data imputation.
AB  - Record linkage algorithms aim to identify pairs of records that correspond to the
      same individual from two or more datasets. In general, fields that are common to
      both datasets are compared to determine which record-pairs to link. The classic
      model for probabilistic linkage was proposed by Fellegi and Sunter and assumes
      that individual fields common to both datasets are completely observed, and that
      the field agreement indicators are conditionally independent within the subsets
      of record pairs corresponding to the same and differing individuals. Herein, we
      propose a novel record linkage algorithm that is independent of these two
      baseline assumptions. We demonstrate improved performance of the algorithm in the
      presence of missing data and correlation patterns between the agreement
      indicators. The algorithm is computationally efficient and can be used to link
      large databases consisting of millions of record pairs. An R-package, corlink,
      has been developed to implement the new algorithm and can be downloaded from the
      CRAN repository.

PMID- 29195709
TI  - Tracking word semantic change in biomedical literature.
AB  - Up to this point, research on written scholarly communication has focused
      primarily on syntactic, rather than semantic, analyses. Consequently, we have yet
      to understand semantic change as it applies to disciplinary discourse. The
      objective of this study is to illustrate word semantic change in biomedical
      literature. To that end, we identify a set of representative words in biomedical
      literature based on word frequency and word-topic probability distributions. A
      word2vec language model is then applied to the identified words in order to
      measure word- and topic-level semantic changes. We find that for the selected
      words in PubMed, overall, meanings are becoming more stable in the 2000s than
      they were in the 1980s and 1990s. At the topic level, the global distance of most
      topics (19 out of 20 tested) is declining, suggesting that the words used to
      discuss these topics are stabilizing semantically. Similarly, the local distance
      of most topics (19 out of 20) is also declining, showing that the meanings of
      words from these topics are becoming more consistent with those of their semantic
      neighbors. At the word level, this paper identifies two different trends in word
      semantics, as measured by the aforementioned distance metrics: on the one hand,
      words can form clusters with their semantic neighbors, and these words, as a
      cluster, coevolve semantically; on the other hand, words can drift apart from
      their semantic neighbors while nonetheless stabilizing in the global context. In
      relating our work to language laws on semantic change, we find no overwhelming
      evidence to support either the law of parallel change or the law of conformity.

PMID- 29195710
TI  - Health IT and inappropriate utilization of outpatient imaging: A cross-sectional
      study of U.S. hospitals.
AB  - OBJECTIVE: To determine whether the use of information technology (IT), measured
      by Meaningful Use capability, is associated with lower rates of inappropriate
      utilization of imaging services in hospital outpatient settings. RESEARCH DESIGN:
      A retrospective cross-sectional analysis of 3332 nonfederal U.S. hospitals using
      data from: Hospital Compare (2011 outpatient imaging efficiency measures), HIMSS
      Analytics (2009 health IT), and Health Indicator Warehouse (market
      characteristics). Hospitals were categorized for their health IT infrastructure
      including EHR Stage-1 capability, and three advanced imaging
      functionalities/systems including integrated picture archiving and communication
      system, Web-based image distribution, and clinical decision support (CDS) with
      physician pathways. Three imaging efficiency measures suggesting inappropriate
      utilization during 2011 included: percentage of "combined" (with and without
      contrast) computed tomography (CT) studies out of all CT studies for abdomen and
      chest respectively, and percentage of magnetic resonance imaging (MRI) studies of
      lumbar spine without antecedent conservative therapy within 60days. For each
      measure, three separate regression models (GLM with gamma-log link function, and
      denominator of imaging measure as exposure) were estimated adjusting for hospital
      characteristics, market characteristics, and state fixed effects. Additionally,
      Heckman's Inverse Mills Ratio and propensity for Stage-1 EHR capability were used
      to account for selection bias. PRINCIPAL FINDINGS: We find support for
      association of each of the four health IT capabilities with inappropriate
      utilization rates of one or more imaging modality. Stage-1 EHR capability is
      associated with lower inappropriate utilization rates for chest CT (incidence
      rate ratio IRR=0.72, p-value <0.01) and lumbar MRI (IRR=0.87, p-value <0.05).
      Integrated PACS is associated with lower inappropriate utilization rate of
      abdomen CT (IRR=0.84, p-value <0.05). Imaging distribution over Web capability is
      associated with lower inappropriate utilization rates for chest CT (IRR=0.66, p
      value <0.05) and lumbar MRI (IRR=0.86, p-value <0.05). CDS with physician
      pathways is associated with lower inappropriate utilization rates for abdomen CT
      (IRR=0.87, p-value <0.01) and lumbar MRI (IRR=0.90, p-value <0.05). All other
      cases showed no association. CONCLUSIONS: The study offers mixed results. Taken
      together, the results suggest that the use of Stage-1 Meaningful Use capable EHR
      systems along with advanced imaging related functionalities could have a
      beneficial impact on reducing some of the inappropriate utilization of outpatient
      imaging.

PMID- 29195711
TI  - Better specification of triggers to reduce the number of drug interaction alerts
      in primary care.
AB  - OBJECTIVE: Drug interaction alerts (drug-drug and drug-disease interaction
      alerts) for chronic medications substantially contribute to alert fatigue in
      primary care. The aim of this study was to determine which events require
      (re)assessment of a drug interaction and whether using these events as triggers
      in clinical decision support systems (CDSSs) would affect the alert rate.
      METHODS: Two random 5% data samples from the CDSSs of 123 community pharmacies
      were used: dataset 1 and 2. The top 10 of most frequent drug interaction alerts
      not involving laboratory values were selected. To reach consensus on events that
      should trigger alerts (e.g. first time dispensing, dose modification) for these
      drug interactions, a two-step consensus process was used. An expert panel of
      community pharmacists participated in an online survey and a subsequent consensus
      meeting. A CDSS with alerts based on the consensus was simulated in both
      datasets. RESULTS: Dataset 1 and 2 together contained 1,672,169 prescriptions
      which led to 591,073 alerts. Consensus on events requiring alerts was reached for
      the ten selected drug interactions. The simulation showed a reduction of the
      alert rate of 93.0% for the ten selected drug interactions (comparable for
      dataset 1 and 2), corresponding with a 28.3% decrease of the overall drug
      interaction alert rate. CONCLUSION: By consensus-based better specification of
      the events that trigger drug interaction alerts in primary care, the alert rate
      for these drug interactions was reduced by over 90%. This promising approach
      deserves further investigation to assess its consequences and applicability in
      daily practice.

PMID- 29195712
TI  - Arthrodesis Versus Carpometacarpal Preservation in Key-Grip Procedures in
      Tetraplegic Patients: A Comparative Study of 40 Cases.
AB  - PURPOSE: Constructing a lateral key pinch (KP) is a universal aim of any
      functional upper limb surgery program for tetraplegia. Three stages are required:
      (1) activating the pinch mechanism by flexor pollicis longus tenodesis to the
      radius or by tendon transfer to the flexor pollicis longus, (2) simplifying the
      polyarticular chain, and (3) positioning the thumb column. We compared 2
      techniques for accomplishing the latter stage, 1 utilizing arthrodesis of the
      carpometacarpal joint (CMC) and 1 that did not require arthrodesis of the CMC.
      MATERIALS AND METHODS: We reviewed 40 cases of KP reconstruction at a mean follow
      up of 7.4 years: 17 who had undergone CMC arthrodesis and 23 without CMC
      arthrodesis. In this group, an abductor pollicis longus tenodesis was necessary
      to properly position the thumb column in 17 patients. RESULTS: Active KP cases
      with CMC arthrodesis were significantly stronger than those without an
      arthrodesis. For passive KP cases, the difference between those cases with CMC
      arthrodesis and those without was not significant. Regarding opening, for active
      KP cases with CMC preservation alone, the mean distance between the thumb pulp
      and the index finger was 4.0 cm at rest and 5.8 cm when passively grasping large
      objects; for active KP cases without arthrodesis, these values were 3.4 and 6.8
      cm, respectively, with the wrist in flexion. For passive KP cases, these values
      were 2.2 and 3.5 cm with CMC arthrodesis compared with 2.4 and 6.9 cm without
      arthrodesis. Overall, 23.5% of patients with CMC arthrodesis could not maintain
      contact between the thumb and the index finger compared with 30.4% without
      arthrodesis. CONCLUSIONS: Active KP is stronger with than without CMC
      arthrodesis; however, the KP reconstruction does not open as far when grasping
      large objects. For passive KP, CMC arthrodesis significantly limits passive
      opening, with no gain in strength. Neither technique is superior in terms of KP
      stability. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 29195713
TI  - Generic antiretroviral drug use in HIV-infected patients: A cohort study from the
      French health insurance database.
AB  - OBJECTIVE: This study aimed to estimate the rate of generic users among HIV
      infected patients treated by antiretroviral (ARV) drugs potentially substitutable
      and to determine factors associated with switch from brand to generic ARV in real
      life settings in a French region. METHODS: Cohort of HIV-infected patients aged
      of >=18 years, exposed to at least one of the generic of lamivudine (3TC
      150mg/300mg), zidovudine/lamivudine (AZT-200mg/3TC-150mg), nevirapine (NVP
      200mg), efavirenz (EFV-600mg) and those exposed to brand 3TC, AZT/3TC, NVP, EFV,
      the fixed-dose combination abacavir/lamivudine (ABC/3TC) or the single-tablet
      regimen efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF) as recorded in the French
      health insurance database between January 2012 and May 2015 were included.
      Factors associated with switch (for each generic versus its brand drug; and for
      situation requiring breaking the combination) were investigated through a
      logistic regression. RESULTS: Among the 1539 patients likely to switch from brand
      ARV drugs, only 165 (11%) were exposed to generics. For EFV users, switch from
      brand to generic was associated with age (aOR=1.04 [CI: 1.00-1.08]). For ABC/3TC
      users, switch was significantly more frequent in patients receiving a monthly
      average of more than two non-ARV drugs (3.08 [1.42-6.68]) and whose regimen
      contained a non-nucleoside reverse transcriptase inhibitor (NNRTI) as index
      medication (3rd agent) (5.68 [2.68-11.39]). By contrast, switch was less frequent
      in AZT/3TC users exposed to drugs used in digestive disorders (0.39 [0.18-0.88])
      or analgesics (0.42 [0.20-0.90]). CONCLUSION: Treatment-experienced HIV patients
      whose disease has been stabilized (less comorbidities) are more likely to switch
      to generic antiretroviral drugs.

PMID- 29195714
TI  - [Gastric acid rebound after a proton pump inhibitor: Narrative review of
      literature].
AB  - BACKGROUND: Since the introduction of the first proton pump inhibitor (PPI) 20
      years ago, studies have examined the presence of a rebound effect when this
      treatment is discontinued. These studies are heterogeneous and contradictory: the
      last literature review on the rebound in gastric acidity dates from 2006 and did
      not allow to conclude on the subject. Our objective was to carry out an up-to
      date literature review on the existence and characteristics of this gastric acid
      rebound at the end of PPIs. METHODS: We conducted a review of the literature on
      the gastric acid rebound, without excluding the design of the studies. The
      Medline(r) databases (PubMed), ISI (Web Of Science) and Google Scholar were
      queried using the following equation: ("inhibitor proton pump" OR omeprazole OR
      esomeprazole OR lansoprazole OR pantoprazole OR rabeprazole) AND "rebound" AND
      "Acid hypersecretion". Only studies with a measure (whatever it was) before and
      after treatment were analyzed. RESULTS: Of the 131 publications identified, 10
      were selected. The design of the studies was very heterogeneous. Five studies
      concluded a rebound effect. Studies with a treatment duration of less than 4
      weeks did not demonstrate a rebound effect. The colonization with Helicobacter
      pylori masked the appearance of the rebound. CONCLUSION: Daily PPI exposure for
      more than 4 weeks is likely to trigger a rebound of acid hypersecretion about 15
      days after discontinuation, and lasting from a few days to several weeks
      depending on the duration of the exposure.

PMID- 29195715
TI  - Utilization of a lateral flow colloidal gold immunoassay strip based on surface
      enhanced Raman spectroscopy for ultrasensitive detection of antibiotics in milk.
AB  - An ultrasensitive method for the detection of antibiotics in milk is developed
      based on inexpensive, simple, rapid and portable lateral flow immunoassay (LFI)
      strip, in combination with high sensitivity surface-enhanced Raman spectroscopy
      (SERS). In our strategy, an immunoprobe was prepared from colloidal gold (AuNPs)
      conjugated with both a monoclonal antibody against neomycin (NEO-mAb) and a Raman
      probe molecule 4-aminothiophenol (PATP). The competitive interaction with
      immunoprobe between free NEO and the coated antigen (NEO-OVA) resulted in the
      change of the amount of the immobilized immunoprobe on the paper substrate. The
      LFI procedure was completed within 15min. The Raman intensity of PATP on the test
      line of the LFI strip was measured for the quantitative determination of NEO. The
      IC50 and the limit of detection (LOD) of this assay are 0.04ng/mL and 0.216pg/mL
      of NEO, respectively. There is no cross-reactivity (CR) of the assay with other
      compounds, showing high specificity of the assay. The recoveries for milk samples
      with added NEO are in the range of 89.7%-105.6% with the relative standard
      deviations (RSD) of 2.4%-5.3% (n=3). The result reveals that this method
      possesses high specificity, sensitivity, reproducibility and stability, and can
      be used to detect a variety of antibiotic residues in milk samples.

PMID- 29195716
TI  - The impact of the recommendation of routine rotavirus vaccination in Germany: An
      interrupted time-series analysis.
AB  - BACKGROUND: Rotavirus is a highly contagious virus causing gastroenteritis,
      mostly in children under the age of 5. Since 2006, two vaccines are available in
      Germany. In 2013, these were included into the German national vaccination
      schedule. The aim of this intervention is to reduce the incidence and
      hospitalization among children under 5 years caused by rotavirus. The
      effectiveness of the intervention was analyzed in this study. METHODS: National
      surveillance data of laboratory confirmed rotavirus infections among children
      under the age of 5 were analyzed using interrupted time-series analysis. Weekly
      incidence from 2011 to 2017 and monthly hospital discharge rates from 2005 to
      2015 were analyzed using a segmented generalized linear model with Poisson
      distribution. RESULTS: After adjusting for seasonal effects the incidence were
      approximately 22% (95% CI: 13.2-30.1) lower than expected following the
      intervention. The hospitalizations were approximately 27% (95% CI: 14.9-39.7)
      lower than expected following the intervention. The long-term effects of the
      intervention were nearly zero. The incidence changed in trend by -0.2% (95% CI: 
      0.1 to (-0.3)) and the hospitalizations by +0.2% (95% CI: 1.2-(-0.8)) following
      the intervention. CONCLUSION: After the inclusion of the vaccines into the
      national vaccination schedule significant immediate effects of this intervention
      were found. The weekly incidences and monthly hospitalization caused by the
      rotavirus were more than 20% lower than expected. The long-term effects of the
      intervention however were found to be nearly zero. This could be caused by a low
      vaccination rate in the German population.

PMID- 29195717
TI  - The efficacy of two different dosages of hepatitis B immunoglobulin combined with
      hepatitis B vaccine in preventing mother-to-child transmission of hepatitis B
      virus: A prospective cohort study.
AB  - BACKGROUND/AIMS: A birth dose of hepatitis B immunoglobulin (HBIG), in
      combination with hepatitis B vaccine (HepB), is recommended for infants born to
      hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage
      of HBIG remains to be resolved. This prospective cohort study aimed to compare
      the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child
      transmission (MTCT) of HBV. METHODS: From 2009 to 2011, we prospectively enrolled
      mother-infant pairs with positive maternal HBsAg in China. Infants were assigned
      to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to
      maternal numbering, followed by completion of the 3-dose 10 MUg HepB series. At 7
      months, post-vaccination serologic testing (PVST) was performed in 545 and 632
      infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529
      were followed up to 12 months. RESULTS: Maternal and birth characteristics were
      comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the
      rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and
      200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU
      HBIG group became newly infected at 12 months. The antibody to hepatitis B
      surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2%
      (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704),
      and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12
      months (p = .266). The anti-HBs geometric mean concentrations were comparable
      between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12
      months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407). CONCLUSIONS: One birth dose
      of 100 IU HBIG, combined with the HepB series, might be enough for preventing
      MTCT of HBV in infants born to HBsAg-positive mothers.

PMID- 29195719
TI  - What do health coaches do? Direct observation of health coach activities during
      medical and patient-health coach visits at 3 federally qualified health centers.
AB  - OBJECTIVE: To examine activities of health coaches during patient medical visits
      and when meeting one-on-one with patients at 3 urban federally qualified health
      centers. METHODS: Encounters were videotaped and transcribed. Data was analyzed
      using a matrix analysis approach that allowed a priori identification of expected
      categories of activity, based on the health coach training model and previously
      developed conceptual framework, which were modified based on activities observed.
      RESULTS: A total of 10 medical visits (patient, clinician and health coach), and
      8 patient-coach visits were recorded. We identified 9 categories common to both
      medical and patient-coach visits and 2 categories unique to the medical visit.
      While observed activities were generally consistent with expected categories,
      some activities were observed infrequently or not at all. We also observed
      additional activity categories, including information gathering and personal
      conversation. The average amount of time spent on some categories of coaching
      activities differed substantially between medical visits and patient-coach
      visits. CONCLUSIONS: Health coaching activities observed differed in several
      respects to those expected, and differed between medical visits and coaching only
      visits. PRACTICE IMPLICATIONS: These results provide insights into health
      coaching behaviors that can be used to inform training and improve utilization of
      health coaches in practice.

PMID- 29195718
TI  - Patient, caregiver and physician perspectives on participating in a thoracic
      rapid tissue donation program.
AB  - OBJECTIVE: The collection of posthumous tissue from advanced stage lung cancer
      patients is beneficial to medical science. Recruiting living patients to a Rapid
      Tissue Donation Program (RTD) poses several psychosocial challenges and little is
      known about perceptions of joining this type of program. This study qualitatively
      examined perceptions of advanced stage lung cancer patients (n=14) participating
      in a lung cancer RTD program, their NoK (n=11), and physicians (n=6) at the
      Thoracic Oncology Clinic at H. Lee Moffitt Cancer Center & Research Institute,
      Tampa, Florida USA. METHODS: Semi-structured interviews were conducted with
      participants and interview transcripts were analyzed using the constant
      comparison method. RESULTS: Majority of patients joined to give back to research,
      discussed participation with family members, and desired for family to receive
      information about the use of the tissue after their death. All participating NoK
      were supportive of their family member's decision. Physicians described the
      program as running smoothly, but provided suggestions for process improvements.
      CONCLUSION: Participants joined with intention to give back to research community
      and families were supportive of loved one's participation in RTD. Physicians
      agreed with overall process. PRACTICE IMPLICATIONS: Key factors for a successful
      RTD program is tailoring to institutional and individual needs.

PMID- 29195720
TI  - Letter to the Editor: Serum surfactant protein D predicts the outcome of patients
      with idiopathic pulmonary fibrosis treated with pirfenidone.

PMID- 29195721
TI  - Port-a-CathTM partial rupture in a low-grade pinch-off syndrome.

PMID- 29195722
TI  - Autologous dermis - Fat grafts as primary and secondary orbital transplants
      before rehabilitation with artificial eyes.
AB  - OBJECTIVE: The aim of this study was to examine the role of autologous dermis-fat
      grafts in the reconstruction of orbital soft-tissue defects. PATIENTS: Thirty-six
      patients (3-84 years) were enrolled in this retrospective study from 2002 to
      2014. The dermis-fat graft was primarily transplanted in seven cases, and
      secondarily in 29 patients. All the patients were evaluated for complications,
      adequate prosthetic cavity, possibility of artificial eye supply and movement, as
      well as cosmetic results. Follow-up periods ranged from 25 to 144 months.
      RESULTS: All the patients could be supplied with an artificial eye in the long
      term after dermis-fat transplantation. The clinical evaluation revealed 17
      complications allocated to 11 patients. A major complication occurred in three
      patients (8.3%) so that a surgical correction was necessary. Thirty-three
      patients (91.7%) showed an aesthetically stable long-term outcome. CONCLUSION:
      Dermis-fat grafts for reconstruction of anophthalmic orbit represent a reliable
      method with a low complication rate and good cosmetic and functional results. The
      graft can be used as primary and secondary transplants. The stable long-term
      results and high aesthetic satisfaction lead us to recommend this method as a
      routine operation.

PMID- 29195723
TI  - A non-language-specific speech test to evaluate the speech of cleft patients from
      different language and cultural backgrounds - A pilot study.
AB  - Cleft speech tests are not universally available. We developed a tool to fill
      this gap, especially in the context of a cleft mission setting. We performed a
      pilot study to evaluate the test's ability to differentiate between the speech of
      cleft patients and healthy individuals from three different language backgrounds.
      We used 78 made-up, nonsensical syllables to evaluate hypernasality, nasal
      emissions, and consonant errors. Cleft (n = 41) and non-cleft (n = 39)
      individuals from three countries were included in this study. Two speech and
      language pathologists, blinded to the examination, rated the audio recording
      independently. Patients from Germany (n = 12; mean age 15.2), Iran (n = 14; mean
      age 7), and India (n = 15; mean age 14.7 years) were evaluated. We observed a
      significant difference in each category (p < 0.05) between patients and control
      subjects of the same language and cultural background. Hypernasality was affected
      the most. The test proved to possess the correct phonetic characteristics to
      reveal and provoke relevant cleft speech pathologies independent of cultural and
      language backgrounds. The test sounds posed no articulatory difficulties to non
      cleft individuals, with some exceptions regarding non-specific consonant errors.
      A comparison with other existing tests will further illuminate its value as a
      speech test.

PMID- 29195724
TI  - Sensing of Cytoskeletal Forces by Asymmetric Adherens Junctions.
AB  - Within tissues, key cellular adaptations occur via mechanotransduction responses
      at cell-cell junctions. Adherens junctions (AJs) typically form between cells as
      a result of the binding of cadherin receptors of the same type (homotypic), and
      are linked to the force-propagating and -generating actomyosin cytoskeleton.
      Recent studies have found that AJs maintain monolayer integrity in dynamic
      tissues and drive collective cell behavior by converting into asymmetric
      remodeling entities. Here, we overview the molecular processes that may explain
      how asymmetric cell-cell junctions sense differences in cytoskeletal geometry
      between cells. We discuss the link between cadherin-complex dynamics and the
      actomyosin cytoskeleton at asymmetric cell-cell junctions. We then outline the
      role of Bin/Amphiphysin/Rvs (BAR) proteins, cytoplasmic regulators of endocytosis
      and cytoskeletal dynamics that sense force-induced membrane curvature, at AJs
      undergoing asymmetric remodeling. Lastly, we highlight the physiological
      importance of junctional asymmetry for epithelial and vascular tissue and discuss
      its potential role in disease.

PMID- 29195725
TI  - Benefits of a bedtime routine in young children: Sleep, development, and beyond.
AB  - This paper presents a conceptual model and reviews the empirical evidence to
      support a nightly bedtime routine as a key factor in the promotion of not only
      healthy sleep, but also of broad development and wellbeing in early childhood. A
      bedtime routine embodies the characteristics of nurturing care and early child
      stimulation, which are deemed to be essential for positive outcomes, especially
      for at-risk children. Furthermore, common, adaptive components of a bedtime
      routine can contribute to an array of positive developmental outcomes beyond
      improved sleep, inclusive of language development, literacy, child emotional and
      behavioral regulation, parent-child attachment, and family functioning, among
      other outcomes. These bedtime routine components include activities in the broad
      domains of nutrition (e.g., feeding, healthy snack), hygiene (e.g., bathing, oral
      care), communication (e.g., reading, singing/lullabies) and physical contact
      (e.g., massage, cuddling/rocking). A bedtime routine can provide multiple
      benefits to child and family functioning at a time of day that many parents are
      present with their children. Although additional research on hypothesized routine
      related child outcomes and mechanisms of action are needed, promoting a bedtime
      routine may be a feasible and cost-effective method to promote positive early
      childhood development worldwide, particularly for socioeconomically disadvantaged
      and other at-risk young children.

PMID- 29195726
TI  - Cardiovascular effects of oral appliance therapy in obstructive sleep apnea: A
      systematic review and meta-analysis.
AB  - Obstructive sleep apnea (OSA) is associated with increased cardiovascular
      morbidity and mortality. This study systematically reviews the effects of oral
      appliance therapy (OAT) on a broad spectrum of cardiovascular outcomes. A
      literature search was performed up to December 31st 2016. Twenty-five relevant
      full-text articles were retrieved. Sixteen articles were considered
      methodologically sufficient, including 11 randomized controlled trials. Pooled
      data of the RCTs showed significant reductions in daytime systolic and diastolic
      blood pressure compared to baseline, but no significant reductions in heart rate,
      except for daytime heart rate when compared to inactive/placebo OAT. OAT and
      continuous positive airway pressure (CPAP) were equally effective in reducing
      blood pressure. Studies assessing the effect of OAT on heart rate variability,
      circulating cardiovascular biomarkers, and endothelial function and arterial
      stiffness, generally involved small numbers of patients, and were heterogeneous
      and inconclusive. Studies assessing the effect of OAT on cardiac function showed
      no effects on echocardiographic outcomes. One observational study showed that OAT
      was as effective as CPAP in reducing cardiovascular death. It could be speculated
      that OAT may lead to a reduction in long-term cardiovascular morbidity and
      mortality in OSA patients. However, further methodologically high quality,
      longitudinal studies are warranted to address this key question.

PMID- 29195728
TI  - Old journal, new media.

PMID- 29195727
TI  - Clinical and imaging findings of pattern dystrophy subtypes; Diagnostic errors
      and unnecessary treatment in clinical practice.
AB  - PURPOSE: To evaluate the clinical and multimodal imaging findings of various
      pattern dystrophy (PD) subtypes and report the initial misdiagnosis rate of PD
      patients resulting in unnecessary treatment in actual clinical practice. METHODS:
      Retrospective, observational study. Forty eyes of 24 patients with PD were
      included. The distribution of PD subtypes, optical coherence tomography (OCT) and
      fundus autofluorescence (FAF) findings, initial misdiagnoses, revised diagnoses,
      duration between misdiagnosis and revised diagnosis, and unnecessary treatments
      administered were evaluated over this time-period. RESULTS: Twenty-eight eyes
      (70%) showed adult-onset foveomacular vitelliform dystrophy, 6 eyes (15%) showed
      butterfly PD (BPD), 4 eyes (10%) showed reticular PD, and 2 eyes (5%) showed PD
      simulating fundus flavimaculatus and BPD mixed type PD. Most of the patients
      showed various types of hyperreflective material in the subretinal space on OCT,
      and hyperautofluorescence on FAF imaging. Eighteen eyes (45%) had a true PD
      diagnosis initially, whereas 22 (55%) of them were misdiagnosed as age-related
      macular degeneration, central serous chorioretinopathy, or non-specific RPE
      change. The mean duration between the initial and revised diagnosis was 18.7+/
      16.8 months. In addition, 5 eyes in the misdiagnosed group underwent intravitreal
      anti-vascular endothelial growth factor treatment during this period. CONCLUSION:
      Pattern dystrophies are a heterogeneous group of macular disorders which may
      mimic several macular diseases. By knowing the multimodal imaging findings,
      especially the distinctive FAF findings of the PDs, we may easily diagnose the
      disease and save our patients from unnecessary treatments.

PMID- 29195729
TI  - Orthostatic hypotension in Parkinson disease: Impact on health care utilization.
AB  - INTRODUCTION: Orthostatic hypotension (OH) represents a frequent yet overlooked
      source of disability in Parkinson disease (PD). In particular, its impact on
      health care utilization has been insufficiently examined. We sought to determine
      the differential health care utilization in PD patients with (PDOH+) and without
      OH (PDOH-). METHODS: We quantified the emergency room (ER) visits,
      hospitalizations, outpatient clinic evaluations, phone calls, and e-mails from PD
      patients on whom supine and orthostatic blood pressure (BP) measurements were
      obtained during routine clinical practice between June 2013 and July 2016.
      Comparative costs between PDOH+ and PDOH- were adjusted for age, disease
      duration, motor severity, levodopa equivalent daily dose, and Montreal Cognitive
      Assessment. RESULTS: From a total of 317 PD patients, 29.3% were classified as
      PDOH+ (n = 93) and 70.6% as PDOH- (n = 224) over 30.2 +/- 11.0 months, in which
      there were 247 hospitalizations, 170 ER visits, 2386 outpatient evaluations, and
      4747 telephone calls/e-mails. After-adjusting for relevant covariates, PDOH+ was
      associated with more hospitalization days (+285%; p = 0.041), ER visits (+152%; p
      = 0.045), and telephone calls/e-mails than PDOH- (+142%; p = 0.009). The overall
      health care-related cost in PDOH+ was 2.5-fold higher than for PDOH- ($25,205 +/-
      $6546 vs. $9831 +/- $4167/person/year; p = 0.037). CONCLUSION: OH increases
      health care utilization in PD independently from age, disease duration, motor
      severity, dopaminergic treatment, and cognitive function.

PMID- 29195730
TI  - Tobacco smoking and electronic cigarette: two sides of the same coin?

PMID- 29195731
TI  - Pharmaceutical interventions in mental health: A review of the literature to
      support evidence-informed policymaking.
AB  - BACKGROUND: Pharmaceutical interventions may have an impact on different
      treatment aspects, such as therapy adherence, reducing the number of different
      medications in use and lowering treatment costs. OBJECTIVE: Identify
      pharmaceutical interventions in the mental health field and their possible
      application in Brazilian public mental health services, considering the evidence
      based model to establish implementation options. METHODS: A structured search of
      the literature was performed in the Pubmed (Medline), Cochrane, PsycINFO and
      Lilacs databases to identify the main pharmaceutical intervention studies
      conducted in the mental health area. The articles selected were evaluated
      according to the quality of the evidence. The current laws and public database
      were researched to collect information on services and procedures provided by the
      Brazilian units, known as CAPS, and the number the pharmacists allocated to them.
      The proposal to synthesize the results of pharmaceutical interventions in Brazil
      was based on SUPPORT methodology items to prepare evidence-based policies.
      RESULTS: A total of 1442 studies were identified, 18 of which were included.
      Several interventions are reported in the literature, educational interventions
      being frequently cited. However, there is a need for further studies with more
      methodological rigor. The number of pharmacists working in the CAPS is
      insufficient to cover all the services, since only 26.5% of CAPS employ
      pharmacists, who work an average of 29 (+/-11.1) hours a week. Three options were
      formulated to implement interventions in the Brazilian context that consider
      including pharmacists on the basic team of CAPS professionals and educational
      interventions through pharmacist training. CONCLUSIONS: The present study could
      support the establishment of health policies, based on a synthesis of the
      evidence, contextualization of the current situation, given the absence of local
      evidence, and a discussion of the options available to implement pharmaceutical
      interventions in the Brazilian health system. Organizational changes in CAPS are
      needed to broaden pharmacist participation on the multidisciplinary team.

PMID- 29195732
TI  - Does Treatment of the Tibia Matter in Bipolar Chondral Defects of the Knee?
      Clinical Outcomes with Greater Than 2 Years Follow-up.
AB  - PURPOSE: To compare the osteochondral allograft (OCA) outcomes of bipolar defects
      with isolated femoral defects and to investigate the optimal treatment of bipolar
      defects by comparing femoral OCA with tibial debridement to femoral OCA and
      tibial microfracture. METHODS: A series of patients with 2-year follow-up from
      March 2004 to September 2015 after femoral OCA for bipolar chondral defects was
      identified. Group 1 contained patients with tibial defects treated with
      debridement and group 2 contained patients with microfractured tibial defects. A
      third group (group 3) with isolated femoral defects treated with OCA was
      identified and matched by gender, body mass index (BMI), laterality, and OCA size
      to groups 1 and 2. Patient-specific, defect-specific, intraoperative, and
      postoperative data including patient-reported outcomes were collected on all
      patients. The study groups were compared using analyses of variance, paired
      sample t tests, and chi-square analyses. RESULTS: Thirty-six patients who had
      femoral OCA for bipolar lesions were identified with 20 patients in group 1 and
      16 patients in group 2. Group 3 had 20 patients. There were no differences
      between the 3 groups in terms of gender (P = .616), BMI (P = .271), number of
      previous surgeries (P = .451), femoral or tibial defect size (P = .296), and OCA
      size (P = .981). Preoperative to postoperative patient-reported clinical outcomes
      (PROs) revealed statistical and clinically meaningful improvement in all 3
      groups, but did not differ between groups. Patient-specific and defect-specific
      factors did not correlate with PROs. The graft survivorship for group 1 was 85%
      at 4.5 years, 100% for group 2 at 2.5 years, and 95% for group 3 at 3.8 years.
      CONCLUSIONS: Regardless of tibial treatment, patients with bipolar defects
      treated with femoral OCA have clinically meaningful improvements in PROs and
      excellent graft survivorship comparable to isolated femoral OCAs at more than 2
      years. LEVEL OF EVIDENCE: Level III, case-control study.

PMID- 29195733
TI  - Changes in body mass index and mid-upper arm circumference in relation to all
      cause mortality in older adults.
AB  - BACKGROUND & AIMS: The assessment of weight loss as an indicator of poor
      nutritional status in older persons is currently widely applied to establish risk
      of mortality. Little is known about the relationship between changes in mid-upper
      arm circumference (MUAC) and mortality in older individuals. The aim of the
      present study was to examine the association between 3-year change in MUAC and 20
      year mortality in community-dwelling older adults and compare this to the
      association between body mass index (BMI) change and mortality. METHODS: Data on
      changes in MUAC (cm) and BMI (kg/m2), covariates, and mortality were available
      for 1307 Dutch older adults (49.7% men) aged 65 years and older in 1995/96 (mean
      75.6 years, SD 6.5) from Longitudinal Aging Study Amsterdam (LASA).
      Anthropometric measurements were performed in 1992/93 with repeated measurements
      in 1995/96 (baseline), and a mortality follow up until July 2015. BMI and MUAC
      change were divided into quintiles, with the quintile including zero defined as
      the reference category. Cox regression analyses were performed to examine the
      associations of 3-year changes in MUAC and BMI with subsequent 20-year all-cause
      mortality, adjusted for demographic and health factors. Age, sex and initial
      measurement of BMI and MUAC (1992/93) were tested for effect modification (P =
      <0.10). RESULTS: Mean baseline BMI was 26.7 kg/m2 (SD 4.2) with a 3-year change
      of -0.2 (SD 1.5). Mean baseline MUAC was 30.5 cm (SD 3.5) with a 3-year change of
      -0.8 (SD 1.6). Age, sex, and BMI and MUAC 3 years prior were effect modifiers in
      the associations between change in anthropometric measurement and mortality.
      Decrease in MUAC was not associated with mortality in persons with a higher
      initial MUAC (>=31 cm), while for persons with a lower initial MUAC, a decrease
      in MUAC of <=-2.15 was associated with increased mortality risk (HR 1.54; 95% CI:
      1.14-2.09), also when further stratified on median age and sex. In stratified
      analysis of BMI change for median initial BMI (26.5) and additionally stratified
      for median age and sex, the associations between a BMI decrease of <=-1.19 and
      mortality fluctuated, mostly statistically not significant. No associations were
      found for gain in MUAC or BMI. CONCLUSIONS: Given that MUAC loss is more strongly
      and consistently associated with an increased mortality risk in older individuals
      with a low initial MUAC compared to BMI loss, this may be a more recommendable
      measure to use in clinical practice for assessing poor nutritional status,
      instead of weight loss.

PMID- 29195734
TI  - Discussion.

PMID- 29195735
TI  - Benefit of social media on patient engagement and satisfaction: Results of a 9
      month, qualitative pilot study using Facebook.
AB  - BACKGROUND: Despite the potential benefits of social media, health care providers
      are often hesitant to engage patients through these sites. Our aim was to explore
      how implementation of social media may affect patient engagement and
      satisfaction. METHODS: In September 2016 a Facebook support group was created for
      liver transplant patients to use as a virtual community forum. Data including
      user demographics and group activity were reviewed. A survey was conducted
      evaluating users' perceptions regarding participation in the group. RESULTS: Over
      9 months, 350 unique users (50% liver transplant patients, 36%
      caregivers/friends, 14% health care providers) contributed 339 posts, 2,338
      comments, and 6,274 reactions to the group; 98% of posts were reacted to or
      commented on by other group members. Patients were the most active users compared
      with health care providers and caregivers. A total of 95% of survey respondents
      reported that joining the group had a positive impact on their care; and 97%
      reported that their main motivation for joining was to provide or receive support
      from other patients. CONCLUSION: This pilot study indicates that the integration
      of social media into clinical practice can empower surgeons to synthesize
      effectively a patient support community that augments patient engagement and
      satisfaction.

PMID- 29195737
TI  - Ex-vivo tissue determination of water fraction in associating liver partition
      with portal vein ligation for staged hepatectomy.

PMID- 29195736
TI  - A novel reproducible model of aortic aneurysm rupture.
AB  - INTRODUCTION: Given the unknown biologic antecedents before aortic aneurysm
      rupture, the purpose of this study was to establish a reproducible model of
      aortic aneurysm rupture. METHODS: We fed 7-week-old apolipoprotein E deficient
      mice a high-fat diet for 4 weeks and osmotic infusion pumps containing
      Angiotensin II were implanted. Angiotensin II was delivered continuously for 4
      weeks at either 1,000 ng/kg/min (n = 25) or 2,000 ng/kg/min (n = 29). A third
      group (n = 14) were given Angiotensin II at 2,000 ng/kg/min and 0.2% beta
      aminopropionitrile dissolved in drinking water. Surviving mice were killed 28
      days after pump placement, aortic diameters were measured, and molecular analyses
      were performed. RESULTS: Survival at 28 days was significantly different among
      groups with 80% survival in the 1,000 ng/kg/min group, 52% in the 2,000 ng/kg/min
      group, and only 14% in the Angiotensin II/beta-aminopropionitrile group (P =
      .0001). Concordantly, rupture rates were statistically different among groups (8%
      versus 38% versus 79%, P < .0001). Rates of abdominal aortic aneurysm were 48%,
      55%, and 93%, respectively, with statistically higher rates in the Angiotensin
      II/beta-aminopropionitrile group compared with both the 1,000 ng and 2,000 ng
      Angiotensin II groups (P = .006 and P = .0165, respectively). Rates of thoracic
      aortic aneurysm formation were 12%, 52%, and 79% in the 3 groups with a
      statistically higher rate in the Angiotensin II/beta-aminopropionitrile group
      compared with 1,000 ng group (P < .0001). CONCLUSIONS: A reproducible model of
      aortic aneurysm rupture was developed with a high incidence of abdominal and
      thoracic aortic aneurysm. This model should enable further studies investigating
      the pathogenesis of aortic rupture, as well as allow for targeted strategies to
      prevent human aortic aneurysm rupture.

PMID- 29195738
TI  - A perioperative care map improves outcomes in patients with morbid obesity
      undergoing major surgery.
AB  - BACKGROUND: The surgical management of patients with morbid obesity (body mass
      index >= 40) is notable for a relatively high risk of complications. To address
      this problem, a perioperative care map was developed using precautions and best
      practices commonly employed in bariatric surgery. It requires additional medical
      assessments, sleep apnea surveillance, more stringent guidelines for anesthetic
      management, and readily available bariatric operating room equipment, among other
      items. This care map was implemented in 2013 at 4 major urban teaching hospitals
      for use in patients undergoing all types of nonambulatory surgery with a body
      mass index greater than 40 kg/m2. The impact on patient outcomes was evaluated.
      METHODS: The American College of Surgeons National Surgical Quality Improvement
      Program database was used to compare 30-day outcomes of morbidly obese patients
      before the year 2013 and after the years 2015 care-map implementation. In
      addition, trends in 30-day outcomes for morbidly obese patients were compared
      with those for non-obese patients. RESULTS: Morbidly obese patients, between 2013
      and 2015, saw an adjusted decrease in the rate of unplanned return to the
      operating room (OR = 0.49; P = .039), unplanned readmission (OR = 0.57; P =
      .006), total duration of stay (-0.87 days; P = .009), and postoperative duration
      of stay (-0.69 days; P = .007). Of these, total duration of stay (-0.86 days; P =
      .015), and postoperative duration of stay (-0.69 days; P = .012) improved
      significantly more for morbidly obese patients than for nonmorbidly obese
      patients. CONCLUSION: Outcomes in morbidly obese patients improved from 2013 to
      2015. Implementation of a perioperative care map may have contributed to these
      improvements. The care map should be further investigated and considered for more
      widespread use.

PMID- 29195739
TI  - Comparison of 3D laparoscopic gastrectomy with a 2D procedure for gastric cancer:
      A phase 3 randomized controlled trial.
AB  - OBJECTIVE: To determine the relative safety and efficacy of 3D laparoscopic
      gastrectomy and 2D laparoscopic surgery in patients with gastric cancer.
      BACKGROUND: There is still a lack of randomized controlled trials regarding the
      safety and efficacy of 3D versus 2D laparoscopic surgery for gastric cancer.
      METHODS: A large-scale, phase 3, prospective, randomized controlled trial was
      conducted. (ClinicalTrials.gov number NCT02327481). RESULTS: A total of 438
      patients were randomized (3D group: 219 cases; 2D group: 219 cases) between
      January 1, 2015, and April 1, 2016; 19 patients were excluded. Finally, data from
      419 patients were analyzed (3D group: 211 cases; 2D group: 208 cases). There were
      no differences between the 2 groups regarding the operation time (3D versus 2D,
      176 +/- 35 min vs. 174 +/- 33 min, P = .562). The intraoperative blood loss in
      the 3D group was somewhat less than in the 2D group (61 +/- 83 mL vs. 82 +/- 119
      mL, P = .045). Further analysis suggested that the use of 3D laparoscopic surgery
      was a protective factor against excessive blood loss (>=200 mL). CONCLUSION: 3D
      laparoscopic gastrectomy did not shorten the operation time compared with 2D
      laparoscopic gastrectomy, but provided the benefit of less intraoperative blood
      loss and a lesser occurrence of excessive bleeding than the conventional 2D
      laparoscopic gastrectomy; the clinical value of the difference is limited.

PMID- 29195741
TI  - Ebola virus secreted glycoprotein decreases the anti-viral immunity of
      macrophages in early inflammatory responses.
AB  - During Ebola virus (EBOV) infection, secreted glycoprotein (sGP) is found in
      large quantities in the serum of both patients and infected animal models. It is
      thought to serve as a decoy for anti-EBOV antibodies. Using an in vitro model
      incorporating treatment of non-infected human THP-1 macrophages with recombinant
      EBOV sGP, this study sought to examine the impact of sGP upon key macrophage
      functions. Macrophage polarization and phagocytic capacity of activated
      macrophages were found to be unaltered by sGP treatment. However, treatment with
      sGP inhibited macrophage production of the pro-inflammatory cytokines TNFalpha
      and IL-6 while the yield of anti-inflammatory cytokine, IL-10, remained intact.
      Interestingly, the migratory ability of macrophages was also diminished by sGP,
      potentially due to a decrease in expression of CD11b, a vital macrophage
      integrin. Thus, EBOV sGP may operate to diminish functional contributions of non
      infected macrophages to increase the potential viral dissemination.

PMID- 29195740
TI  - Validation of fragility fractures in primary care electronic medical records: A
      population-based study.
AB  - PURPOSE: Electronic medical records databases use pre-specified lists of
      diagnostic codes to identify fractures. These codes, however, are not specific
      enough to disentangle traumatic from fragility-related fractures. We report on
      the proportion of fragility fractures identified in a random sample of coded
      fractures in SIDIAP. METHODS: Patients>=50 years old with any fracture recorded
      in 2012 (as per pre-specified ICD-10 codes) and alive at the time of recruitment
      were eligible for this retrospective observational study in 6 primary care
      centres contributing to the SIDIAP database (www.sidiap.org). Those with previous
      fracture/s, non-responders, and those with dementia or a serious psychiatric
      disease were excluded. Data on fracture type (traumatic vs fragility), skeletal
      site, and basic patient characteristics were collected. RESULTS: Of 491/616
      (79.7%) patients with a registered fracture in 2012 who were contacted, 331 (349
      fractures) were included. The most common fractures were forearm (82), ribs (38),
      and humerus (32), and 225/349 (64.5%) were fragility fractures, with higher
      proportions for classic osteoporotic sites: hip, 91.7%; spine, 87.7%; and major
      fractures, 80.5%. This proportion was higher in women, the elderly, and patients
      with a previously coded diagnosis of osteoporosis. CONCLUSIONS: More than 4 in 5
      major fractures recorded in SIDIAP are due to fragility (non-traumatic), with
      higher proportions for hip (92%) and vertebral (88%) fracture, and a lower
      proportion for fractures other than major ones. Our data support the validity of
      SIDIAP for the study of the epidemiology of osteoporotic fractures.

PMID- 29195742
TI  - Preclinical models to assess the immunogenicity of AAV vectors.
AB  - Although gene transfer using adeno-associated virus (AAV) vectors has made
      tremendous progress in recent years, challenges remain due to vector-specific
      adaptive immune responses. Specifically, AAV-neutralizing antibodies reduce AAV
      transduction rates, while CD8+ T cells directed to AAV capsid antigens cause
      rejection of AAV-transduced cells. This has been addressed clinically by
      excluding humans with pre-existing AAV-neutralizing antibodies from gene transfer
      trials or by using immunosuppression or reduced doses of vectors expressing
      improved transgene products to blunt or circumvent destructive T cell responses.
      Although these approaches have met with success for treatment of some diseases,
      most notably hemophilia B, they may not be suitable for others. Pre-clinical
      models are thus needed to test alternative options to sidestep pre-existing AAV
      neutralizing antibodies, to prevent their induction following gene transfer and
      to block the detrimental effects of CD8+ T cells directed to AAV capsid antigens.
      This chapter describes some of the available, although not yet perfect, models
      that can assess immune responses to AAV gene transfer.

PMID- 29195743
TI  - Factors Associated With HIV Testing in U.S. Latinos When Language Preference is
      Spanish.

PMID- 29195744
TI  - Discrimination of atypical parkinsonisms with transcranial magnetic stimulation.
AB  - BACKGROUND: Differential diagnosis of atypical parkinsonian disorders, i.e.
      dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) or
      corticobasal syndrome (CBS) still remains problematic. Furthermore, DLB may
      overlap with Alzheimer's disease (AD) in the early stages of disease. OBJECTIVE:
      To determine whether transcranial magnetic stimulation (TMS) can be used to
      classify atypical parkinsonian disorders and AD. METHODS: A paired-pulse TMS
      multi-paradigm approach assessing multiple intracortical circuits, as short
      interval intracortical inhibition-facilitation and short latency afferent
      inhibition, was used to model a decision tree analysis and determine diagnostic
      accuracy in classifying different neurodegenerative disorders. RESULTS: We
      observed a significant impairment in short latency afferent inhibition in AD and
      DLB and a significant impairment in short interval intracortical inhibition
      facilitation in DLB, PSP and CBS patients. These parameters were used to model a
      decision tree analysis which yielded an overall diagnostic accuracy of 88.3%,
      with 90.5% for AD, 85.2% for DLB, 76.0% for CBS-PSP, and 94.9% for healthy
      controls. CONCLUSIONS: The assessment of intracortical connectivity with TMS may
      aid in the differential diagnosis of AD and the atypical parkinsonian disorders.

PMID- 29195745
TI  - Localized Tacrolimus Delivery Repairs the Damaged Central Nervous System.

PMID- 29195747
TI  - Somatic mosaicism for SLC1A1 mutation supports threshold effect and familial
      aggregation in schizophrenia spectrum disorders.

PMID- 29195746
TI  - Association between migrant worker experience, limitations on insurance coverage,
      and hospitalization for schizophrenia in Hunan Province, China.
AB  - BACKGROUND: While transnational migration has been shown to be a risk factor for
      schizophrenia, studies have not examined whether massive internal rural-to-urban
      migration in China in recent years has increased the risk of hospitalization for
      schizophrenia, or schizophrenia symptom severity among migrants. METHOD: In a
      sample of patients acutely hospitalized with schizophrenia in Changsha, Hunan
      Province, China (N=334), the proportion of past migrant workers among patients
      was compared to the proportion of past migrant workers in the general adult
      population of Hunan. Past migrants were also compared to non-migrants on age of
      onset, and on symptom severity using the Positive and Negative Syndrome Scale
      (PANSS). The risk ratio for being a migrant among those hospitalized for
      schizophrenia was stratified by age and gender subgroups. Multiple regression
      analysis was used to evaluate group differences in age of onset and symptoms.
      RESULTS: Of 334 patients diagnosed with schizophrenia hospitalized for <180days,
      150 (44.9%) were identified as having been migrant workers compared to 31.0% in
      the general adult population of Hunan for a risk ratio of 1.45, a risk that was
      higher for women (2.19) than for men (1.09). Migrant workers also had higher
      scores than others on total PANSS symptoms. CONCLUSION: Migrant workers appear to
      be at greater risk of hospitalization for schizophrenia than other residents of
      Hunan and showed more severe psychopathology. These findings may reflect specific
      lack of health insurance coverage for workers migrating to non-native provinces
      in China, thereby delaying access to treatment.

PMID- 29195748
TI  - Hallucinations in Indigenous and non-Indigenous Australians: Findings from the
      second Australian national survey of psychosis.

PMID- 29195749
TI  - Acute colonic distension in a patient with severe muscular dystrophy receiving
      non-invasive positive pressure ventilation.

PMID- 29195750
TI  - Partnership HealthPlan of California: Addressing opioid overuse with behavioral
      design principles.

PMID- 29195751
TI  - Development and Validation of a Phase-Filtered Moving Ensemble Correlation for
      Echocardiographic Particle Image Velocimetry.
AB  - A new processing method for echocardiographic particle image velocimetry
      (EchoPIV) using moving ensemble (ME) correlation with dynamic phase correlation
      filtering was developed to improve velocity measurement accuracy for routine
      clinical evaluation of cardiac function. The proposed method was tested using
      computationally generated echocardiogram images. Error analysis indicated that ME
      EchoPIV yields a twofold improvement in bias and random error over the current
      standard correlation method (betaPairwise = -0.15 vs. betaME = -0.06;
      sigmaPairwise = 1.00 vs. sigmaME = 0.49). Subsequently a cohort of eight patients
      with impaired diastolic filling underwent similar evaluation. Comparison of
      patient EchoPIV velocity time series with corresponding color M-mode velocity
      time series revealed better agreement for ME EchoPIV compared with standard PIV
      processing (RME = 0.90 vs. RPairwise = 0.70). Further time series analysis was
      performed to measure filling propagation velocity and 1-D intraventricular
      pressure gradients. Comparison against CMM values indicated that both
      measurements are completely decorrelated for pairwise processing (R2Vp = 0.15,
      R2IVPD = 0.07), whereas ME processing correlates decently (R2Vp = 0.69, R2IVPD =
      0.69). This new approach enables more robust processing of routine clinical scans
      and can increase the utility of EchoPIV for the assessment of left ventricular
      function.

PMID- 29195752
TI  - A Novel Method of Synovitis Stratification in Ultrasound Using Machine Learning
      Algorithms: Results From Clinical Validation of the MEDUSA Project.
AB  - Ultrasound is widely used in the diagnosis and follow-up of chronic arthritis. We
      present an evaluation of a novel automatic ultrasound diagnostic tool based on
      image recognition technology. Methods used in developing the algorithm are
      described elsewhere. For the purpose of evaluation, we collected 140 ultrasound
      images of metacarpophalangeal and proximal interphalangeal joints from patients
      with chronic arthritis. They were classified, according to hypertrophy size, into
      four stages (0-3) by three independent human observers and the algorithm. An
      agreement ratio was calculated between all observers and the standard derived
      from results of human staging using kappa statistics. Results was significant in
      all pairs, with the highest p value of 3.9 * 10-6. kappa coefficients were lower
      in algorithm/human pairs than between human assessors. The algorithm is effective
      in staging synovitis hypertrophy. It is, however, not mature enough to use in a
      daily practice because of limited accuracy and lack of color Doppler recognition.
      These limitations will be addressed in the future.

PMID- 29195753
TI  - Ultrasound Determination of the Femoral Head-Neck Alpha Angle.
AB  - The femoral head-neck alpha angle is used to quantify the degree of femoral head
      asphericity in patients suspected of cam-type femoroacetabular impingement. The
      measurement was first performed using magnetic resonance imaging and, more
      recently, three-dimensional computed tomography (CT). We set out to determine
      whether the alpha angle could be reliably measured using ultrasound. Patients
      were recruited from a cohort presenting for CT of the hip. Alpha angles were
      calculated following the departmental protocol by institutionally accredited
      radiographers. After the CT, patients were imaged with ultrasound and the alpha
      angle calculated from the ultrasound image by a sonographer blinded to the CT
      result. Statistical comparison of the two methods was performed with the Bland
      Altman test using SPSS (version 21.0, Chicago, USA), and a p < 0.05 afforded
      significance. Twenty-eight patients were recruited. Eleven patients were
      bilateral examinations, providing 39 hips for analysis. There were 15 females and
      13 males, with 21 right and 18 left hips examined. Average patient age (+/
      standard deviation) was 40 y (+/-13.9 y). Mean (+/-standard deviation)
      measurements for CT and ultrasound were 62.5 degrees  (+/-14.2 degrees ) and 64.5
      degrees  (+/-12.6 degrees ), respectively. The mean absolute difference between
      the two methods was 10.5 degrees  (95% confidence interval 6.9 degrees -14.0
      degrees ). Sensitivity of each individual ultrasound measurement was 91.3%. The
      specificity of ultrasound was 43.75%. The positive predictive value was 0.7, and
      the negative predictive value was 0.78. Overall accuracy of the ultrasound
      derived alpha angle was calculated at 0.718. Ultrasound demonstrates good
      sensitivity and good negative predictive value in calculation of the femoral head
      neck alpha angle compared with CT; however, specificity is low. Ultrasound
      measurement of the alpha angle can provide objective evidence of cam-type
      femoroacetabular impingement in symptomatic patients and can direct patients to
      more established imaging techniques where appropriate.

PMID- 29195754
TI  - Determination of Acoustic Cavitation Probabilities and Thresholds Using a Single
      Focusing Transducer to Induce and Detect Acoustic Cavitation Events: I. Method
      and Terminology.
AB  - A method to determine acoustic cavitation probabilities in tissue-mimicking
      materials (TMMs) is described that uses a high-intensity focused ultrasound
      (HIFU) transducer for both inducing and detecting the acoustic cavitation events.
      The method was evaluated by studying acoustic cavitation probabilities in agar
      based TMMs with and without scatterers and for different sonication modes like
      continuous wave, single pulses (microseconds to milliseconds) and repeated burst
      signals. Acoustic cavitation thresholds (defined here as the peak rarefactional
      in situ pressure at which the acoustic cavitation probability reaches 50%) at a
      frequency of 1.06 MHz were observed between 1.1 MPa (for 1 s of continuous wave
      sonication) and 4.6 MPa (for 1 s of a repeated burst signal with 25-cycle burst
      length and 10-ms burst period) in a 3% (by weight) agar phantom without
      scatterers. The method and its evaluation are described, and general terminology
      useful for standardizing the description of insonation conditions and comparing
      results is provided. In the accompanying second part, the presented method is
      used to systematically study the acoustic cavitation thresholds in the same
      material for a range of sonication modes.

PMID- 29195755
TI  - Determination of Acoustic Cavitation Probabilities and Thresholds Using a Single
      Focusing Transducer to Induce and Detect Acoustic Cavitation Events: II.
      Systematic Investigation in an Agar Material.
AB  - In the accompanying article (Part I), a method is described to determine acoustic
      cavitation probabilities in tissue-mimicking materials (TMMs) using a high
      intensity focused ultrasound (HIFU) transducer for both inducing and detecting
      the acoustic cavitation events, and its suitability for different sonication
      modes like continuous wave, single pulses (with pulse lengths from microseconds
      to milliseconds) and repeated burst signals is discussed. In Part II, the use of
      the method for a systematic study of the dependence of the acoustic cavitation
      thresholds in 3% (by weight) agar phantoms on the temporal sonication parameters
      is discussed. The values obtained at a frequency of 1.06 MHz, ranging from (0.58
      +/- 0.12) MPa for a 3-s continuous wave mode sonication to (5.2 +/- 1.0) MPa for
      single shots with a length of 10 wave cycles, are discussed and interpreted on
      the basis of literature values and their self-consistency.

PMID- 29195757
TI  - Bowel Sonoelastography in Patients with Crohn's Disease: A Systematic Review.
AB  - Sonoelastography is an ultrasound-based method for evaluating the biological
      properties of a target tissue. It is commonly used in the diagnosis of liver and
      thyroid disease, but recently its use for monitoring the characteristics of bowel
      wall in patients affected by Crohn's disease (CD) has been proposed. Our aim was
      a systematic review of the use of sonoelastography in patients with CD. An
      initial database search retrieved 32 possible articles. On initial screening, 7
      articles, concerning a total of 129 patients and 154 lesions of the small and
      large bowel, were finally included in the review. The age range varied between 6
      and 53 y, and disease duration ranged between 1 and 623 mo. We collected data on
      the examinations performed (type and time), bowel area considered and parameters
      evaluated. All authors found that elastography correlates well with the degree of
      fibrosis, as wall strain significantly decreases in segments affected by fibrotic
      stenosis. Even though the endpoints proposed in the various articles are
      relatively inhomogeneous and scarcely comparable, we found that sonoelastography
      is a promising tool in the evaluation of patients with CD as it can differentiate
      inflammatory and fibrotic strictures in small case series.

PMID- 29195756
TI  - An Ultrasound Surface Wave Technique for Assessing Skin and Lung Diseases.
AB  - Systemic sclerosis (SSc) is a multi-organ connective tissue disease characterized
      by immune dysregulation and organ fibrosis. Severe organ involvement, especially
      of the skin and lung, is the cause of morbidity and mortality in SSc.
      Interstitial lung disease (ILD) includes multiple lung disorders in which the
      lung tissue is fibrotic and stiffened. The purpose of this study was to translate
      ultrasound surface wave elastography (USWE) for assessing patients with SSc
      and/or ILD via measuring surface wave speeds of both skin and superficial lung
      tissue. Forty-one patients with both SSc and ILD and 30 healthy patients were
      enrolled in this study. An external harmonic vibration was used to generate the
      wave propagation on the skin or lung. Three excitation frequencies of 100, 150
      and 200 Hz were used. An ultrasound probe was used to measure the wave
      propagation in the tissue non-invasively. Surface wave speeds were measured on
      the forearm and upper arm of both left and right arm, as well as the upper and
      lower lungs, through six intercostal spaces of patients and healthy patients.
      Viscoelasticity of the skin was calculated by the wave speed dispersion with
      frequency using the Voigt model. The magnitudes of surface wave speed and
      viscoelasticity of patients' skin were significantly higher than those of healthy
      patients (p <0.0001) for each location and each frequency. The surface wave
      speeds of patients' lung were significantly higher than those of healthy patients
      (p <0.0001) for each location and each frequency. USWE is a non-invasive and non
      ionizing technique for measuring both skin and lung surface wave speed and may be
      useful for quantitative assessment of SSc and/or ILD.

PMID- 29195758
TI  - Light up ADHD: I. Cortical hemodynamic responses measured by functional Near
      Infrared Spectroscopy (fNIRS): Special Section on "Translational and Neuroscience
      Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD. This
      Section of JAD focuses on the relevance of translational and neuroscience studies
      in providing a better understanding of the neural basis of affective disorders.
      The main aim is to briefly summarise relevant research findings in clinical
      neuroscience with particular regards to specific innovative topics in mood and
      anxiety disorders.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a
      neurodevelopmental disorder characterized by deficits in cognitive and emotional
      self-control. Optical technique acquisitions, such as near infrared spectroscopy
      (NIRS), seem to be very promising during developmental ages, as they are non-
      invasive techniques and less influenced by body movements than other neuroimaging
      methods. Recently, these new techniques are being widely used to measure neural
      correlates underlying neuropsychological deficits in children with ADHD. METHODS:
      In a short series of articles, we will review the results of functional NIRS
      (fNIRS) studies in children with ADHD. The present brief review will focus on the
      results of the fNIRS studies that investigate cortical activity during
      neuropsychological and/or emotional tasks. RESULTS: According to the reviewed
      studies, children and adolescents with ADHD show peculiar cortical activation
      both during neurological and emotional tasks, and the majority of the reviewed
      studies revealed lower prefrontal cortex activation in patients compared to
      typically developmental controls. LIMITATIONS: a consistent interpretation of
      these results is limited by the substantial methodological heterogeneity
      including patients' medication status and washout period, explored cerebral
      regions, neuropsychological tasks, number of channels and sampling temporal
      resolutions. CONCLUSIONS: fNIRS seems to be a promising tool for investigating
      neural substrates of emotional dysregulation and executive function deficits in
      individuals with ADHD during developmental ages.

PMID- 29195760
TI  - Disparities in knowledge about the health effects of smoking among adolescents
      following the release of new pictorial health warning labels.
AB  - This paper examined knowledge about the health effects of smoking among health
      equity groups following the 2012 introduction of refreshed pictorial health
      warning labels (HWLs) in Canada. Data are from the 2012/2013 Youth Smoking Survey
      a representative school-based survey of 47,203 adolescents in Grades 6-12 in nine
      provinces. Regression models examined overall knowledge about eight health
      effects of smoking included in the HWLs. Less than one-third of adolescents
      (32.2%) knew that smoking causes vision loss/blindness and 33.7% knew that
      smoking causes bladder cancer. Whereas knowledge was high for lung cancer
      (93.9%), knowledge about other health effects ranged from 52.9% for chronic
      bronchitis/emphysema to 77.6% for gum or mouth disease. Non-smoking adolescents
      who were: susceptible to future smoking, male, ethnic minorities, and who had
      less spending money were significantly less likely to be knowledgeable of the
      health effects of smoking. There were fewer disparities in knowledge about the
      health effects of smoking among smokers. Smokers who bought loose or bagged
      cigarettes rather than cigarettes in packages or cartons were significantly less
      likely to be knowledgeable about the health effects of smoking. There are
      significant disparities in knowledge about the health effects of smoking by
      health equity groups particularly among non-smoking adolescents. Warning labels
      have the potential to reduce disparities in knowledge about the health effects of
      smoking when exposure to the warning labels is universal. Complementary
      strategies such as mass media campaigns are needed to address disparities in
      knowledge.

PMID- 29195761
TI  - Neighbourhood typologies and associations with body mass index and obesity: A
      cross-sectional study.
AB  - Little research has investigated associations between a combined measure of the
      food and physical activity (PA) environment, BMI (body-mass-index) and obesity.
      Cross-sectional data (n=22,889, age 18-86years) from the Yorkshire Health Study
      were used [2010-2013]. BMI was calculated using self-reported height and weight;
      obesity=BMI>=30. Neighbourhood was defined as a 2km radial buffer. Food outlets
      and PA facilities were sourced from Ordnance Survey Points of Interest (PoI) and
      categorised into 'fast-food', 'large supermarkets', 'convenience and other food
      retail outlets' and 'physical activity facilities'. Parks were sourced from Open
      Street Map. Latent class analysis was conducted on these five environmental
      variables and availability was defined by quartiles of exposure. Linear and
      logistic regressions were then conducted for BMI and obesity respectively for
      different neighbourhood types. Models adjusted for age, gender, ethnicity, area
      level deprivation, and rural/urban classification. A five-class solution
      demonstrated best fit and was interpretable. Neighbourhood typologies were
      defined as; 'low availability', 'moderate availability', 'moderate PA, limited
      food', 'saturated' and 'moderate PA, ample food'. Compared to low availability,
      one typology demonstrated lower BMI (saturated, b=-0.50, [95% CI=-0.76, -0.23]),
      while three showed higher BMI (moderate availability, b=0.49 [0.27, 0.72];
      moderate PA, limited food, b=0.30 [0.01, 0.59]; moderate PA, ample food, b=0.32
      [0.08, 0.57]). Furthermore, compared to the low availability, saturated
      neighbourhoods showed lower odds of obesity (OR=0.86 [0.75, 0.99]) while moderate
      availability showed greater odds of obesity (OR=1.18 [1.05, 1.32]). This study
      supports population-level approaches to tackling obesity however neighbourhoods
      contained features that were health-promoting and -constraining.

PMID- 29195762
TI  - Institutionalizing Sex Education in Diverse U.S. School Districts.
AB  - PURPOSE: This paper describes the Working to Institutionalize Sex Education
      (WISE) Initiative, a privately funded effort to support ready public school
      districts to advance and sustain comprehensive sexuality programs, and examines
      the degree to which WISE has been successful in increasing access to sex
      education, removing barriers, and highlighting best practices. METHODS: The data
      for this study come from a set of performance indicators, guidance documents, and
      tools designed for the WISE Initiative to capture changes in sex education
      institutionalization at WISE school districts. The evaluation includes the
      analysis of 186 school districts across 12 states in the U.S. RESULTS: As a
      result of the WISE Initiative, 788,865 unique students received new or enhanced
      sex education in school classrooms and 88 school districts reached their sex
      education institutionalization goals. In addition to these school district
      successes, WISE codified the WISE Method and toolkit-a practical guide to help
      schools implement sex education. CONCLUSIONS: Barriers to implementing sexuality
      education can be overcome with administrative support and focused technical
      assistance and training, resulting in significant student reach in diverse school
      districts nationwide.

PMID- 29195759
TI  - Circadian regulation of glucose, lipid, and energy metabolism in humans.
AB  - The circadian system orchestrates metabolism in daily 24-hour cycles. Such
      rhythms organize metabolism by temporally separating opposing metabolic processes
      and by anticipating recurring feeding-fasting cycles to increase metabolic
      efficiency. Although animal studies demonstrate that the circadian system plays a
      pervasive role in regulating metabolism, it is unclear how, and to what degree,
      circadian research in rodents translates into humans. Here, we review evidence
      that the circadian system regulates glucose, lipid, and energy metabolism in
      humans. Using a range of experimental protocols, studies in humans report
      circadian rhythms in glucose, insulin, glucose tolerance, lipid levels, energy
      expenditure, and appetite. Several of these rhythms peak in the biological
      morning or around noon, implicating earlier in the daytime is optimal for food
      intake. Importantly, disruptions in these rhythms impair metabolism and influence
      the pathogenesis of metabolic diseases. We therefore also review evidence that
      circadian misalignment induced by mistimed light exposure, sleep, or food intake
      adversely affects metabolic health in humans. These interconnections among the
      circadian system, metabolism, and behavior underscore the importance of
      chronobiology for preventing and treating type 2 diabetes, obesity, and
      hyperlipidemia.

PMID- 29195763
TI  - Revisiting the Link Between Depression Symptoms and High School Dropout: Timing
      of Exposure Matters.
AB  - PURPOSE: Recent reviews concluded that past depression symptoms are not
      independently associated with high school dropout, a conclusion that could induce
      schools with high dropout rates and limited resources to consider depression
      screening, prevention, and treatment as low-priority. Even if past symptoms are
      not associated with dropout, however, it is possible that recent symptoms are.
      The goal of this study was to examine this hypothesis. METHODS: In 12
      disadvantaged high schools in Montreal (Canada), all students at least 14 years
      of age were first screened between 2012 and 2015 (Nscreened = 6,773). Students
      who dropped out of school afterward (according to school records) were then
      invited for interviews about their mental health in the past year. Also
      interviewed were matched controls with similar risk profiles but who remained in
      school, along with average not at-risk schoolmates (Ninterviewed = 545).
      Interviews were conducted by trained graduate students. RESULTS: Almost one
      dropout out of four had clinically significant depressive symptoms in the 3
      months before leaving school. Adolescents with recent symptoms had an odd of
      dropping out more than twice as high as their peers without such symptoms
      (adjusted odds ratio = 2.17; 95% confidence interval = 1.14-4.12). In line with
      previous findings, adolescents who had recovered from earlier symptoms were not
      particularly at risk. CONCLUSIONS: These findings suggest that to improve
      disadvantaged youths' educational outcomes, investments in comprehensive mental
      health services are needed in schools struggling with high dropout rates, the
      very places where adolescents with unmet mental health needs tend to concentrate.

PMID- 29195764
TI  - Suicide Screening in Primary Care: Use of an Electronic Screener to Assess
      Suicidality and Improve Provider Follow-Up for Adolescents.
AB  - PURPOSE: The purpose of this study was to assess the feasibility of using an
      existing computer decision support system to screen adolescent patients for
      suicidality and provide follow-up guidance to clinicians in a primary care
      setting. Predictors of patient endorsement of suicidality and provider
      documentation of follow-up were examined. METHODS: A prospective cohort study was
      conducted to examine the implementation of a CDSS that screened adolescent
      patients for suicidality and provided follow-up recommendations to providers. The
      intervention was implemented for patients aged 12-20 years in two primary care
      clinics in Indianapolis, Indiana. RESULTS: The sample included 2,134 adolescent
      patients (51% female; 60% black; mean age = 14.6 years [standard deviation =
      2.1]). Just over 6% of patients screened positive for suicidality. A positive
      endorsement of suicidality was more common among patients who were female,
      depressed, and seen by an adolescent-medicine board-certified provider as opposed
      to general pediatric provider. Providers documented follow-up action for 83% of
      patients who screened positive for suicidality. Documentation of follow-up action
      was correlated with clinic site and Hispanic race. The majority of patients who
      endorsed suicidality (71%) were deemed not actively suicidal after assessment by
      their provider. CONCLUSIONS: Incorporating adolescent suicide screening and
      provider follow-up guidance into an existing computer decision support system in
      primary care is feasible and well utilized by providers. Female gender and
      depressive symptoms are consistently associated with suicidality among
      adolescents, although not all suicidal adolescents are depressed. Universal use
      of a multi-item suicide screener that assesses recency might more effectively
      identify suicidal adolescents.

PMID- 29195765
TI  - Central nervous system blastomycosis diagnosed using the MVista(r) Blastomyces
      quantitative antigen enzyme immunoassay test on cerebrospinal fluid: A case
      report and review of the literature.
AB  - Blastomyces dermatitidis is a thermally dimorphic fungus that is capable of
      causing pulmonary and extra-pulmonary disease, including infections of the
      central nervous system (CNS). Diagnosis of CNS blastomycosis with non-invasive
      testing can be difficult, and a surgical biopsy may ultimately be required for
      microbiological and/or histopathological confirmation. A case of B. dermatitidis
      meningitis is presented where the diagnosis was made by testing cerebrospinal
      fluid (CSF) using the MVista(r) Blastomyces Quantitative Antigen Enzyme
      Immunoassay test. The utility of performing this test on CSF for diagnosis of CNS
      mass lesions/abscesses caused by B. dermatitidis in the absence of associated
      meningitis remains unclear. Cross reaction of the Blastomyces antigen test with
      other dimorphic fungi is a concern, necessitating that positive test results are
      interpreted in the context of the patient's exposure and travel history.

PMID- 29195766
TI  - Dalbavancin is active in vitro against biofilms formed by dalbavancin-susceptible
      enterococci.
AB  - We tested the in vitro activity of dalbavancin, vancomycin and daptomycin against
      83 enterococcal isolates in planktonic and biofilm states. The MIC90 for
      vancomycin-susceptible Enterococcus faecalis was 0.125 and 4MUg/mL for
      dalbavancin and daptomycin, respectively. For vancomycin-resistant Enterococcus
      faecium, the MIC90 was >16 and 2MUg/mL for dalbavancin and daptomycin,
      respectively. Dalbavancin minimum biofilm inhibitory concentrations (MBICs) for
      vancomycin-susceptible and -resistant isolates were <=0.25 and >16MUg/mL,
      respectively. The daptomycin MBIC90 for all isolates was 4MUg/mL. For E. faecalis
      and E. faecium, dalbavancin minimum biofilm bactericidal concentrations (MBBCs)
      for vancomycin-susceptible and -resistant isolates were <=4 and >16MUg/mL,
      respectively, whereas vancomycin MBBCs were >128MUg/mL for all isolates, and
      daptomycin MBBC90 values for both species were 128MUg/mL. In summary, dalbavancin
      exhibited in vitro activity against all tested isolates of vancomycin
      susceptible, but not against vancomycin-resistant enterococci; activity was
      observed in both the planktonic and biofilm states.

PMID- 29195767
TI  - NDM-1 encoded by a pNDM-HN380-like plasmid pNDM-BJ03 in clinical Enterobacter
      cloacae.
AB  - A carbapenemase-producing Enterobacter cloacae hhy03 with a blaNDM-1 and blaSHV
      12-coharboring plasmid was isolated from a sputum specimen of a patient. This is
      the third nucleotide sequence report of blaNDM-1-harboring plasmid from
      Enterobacter cloacae that have caused lethal infections in China, indicating the
      spread of NDM-1 by IncX3 plasmid between Enterobacteriaceae.

PMID- 29195768
TI  - Failure of daptomycin beta-Lactam combination therapy to prevent resistance
      emergence in Enterococcus faecium.
AB  - Daptomycin beta-Lactam combination therapy offers "protection" against daptomycin
      non-susceptibility (DNS) development in Enterococcus faecium. We report failure
      of this strategy and the importance of source control. Mutations were detected in
      the LiaF and cls genes in DNS isolates. A single DNS isolate contained an
      unrecognized mutation, which requires confirmation.

PMID- 29195769
TI  - Mucormycete Infiltration in the Cardiac Conduction System.

PMID- 29195770
TI  - Comparability of Automated Office Blood Pressure to Daytime 24-Hour Ambulatory
      Blood Pressure-Reply to Editorial from Dr Myers.

PMID- 29195771
TI  - [Sedimentary cutaneous lesions].

PMID- 29195772
TI  - The evolution of toxicant resistance in daphniids and its role on surrogate
      species.
AB  - Prolonged exposure to a disturbance such as a toxicant has the potential to
      result in rapid evolution to toxicant resistance in many short-lived species such
      as daphniids. This evolution may allow a population to persist at higher levels
      of the toxicant than is possible without evolution. Here we apply evolutionary
      game theory to a Leslie matrix model for a daphniid population to obtain a
      Darwinian model that couples population dynamics with the dynamics of an evolving
      trait. We use the Darwinian model to consider how the evolution of resistance to
      the lethal or sublethal effects of a disturbance may change the population
      dynamics. In particular, we determine the conditions under which a daphniid
      population can persist by evolving toxicant resistance. We then consider the
      implications of this evolution in terms of the use of daphniids as surrogate
      species. We show for three species of daphniids that evolution of toxicant
      resistance means that one species may persist while another does not. These
      results suggest that toxicant studies that do not consider the potential of a
      species (or its surrogate) to develop toxicant resistance may not accurately
      predict the long term persistence of the species.

PMID- 29195773
TI  - Cognitive deficits in bipolar disorders: Implications for emotion.
AB  - Prominent cognitive deficits have been documented in bipolar disorder, and
      multiple studies suggest that these deficits can be observed among non-affected
      first-degree relatives of those with bipolar disorder. Although there is
      variability in the degree of cognitive deficits, these deficits are robustly
      relevant for functional outcomes. A separate literature documents clear
      difficulties in emotionality, emotion regulation, and emotion-relevant
      impulsivity within bipolar disorder, and demonstrates that these emotion-relevant
      variables are also central to outcome. Although cognitive and emotion domains are
      typically studied independently, basic research and emergent findings in bipolar
      disorder suggest that there are important ties between cognitive deficits and the
      emotion disturbances observed in bipolar disorder. Understanding these
      relationships has relevance for fostering more integrative research, for
      clarifying relevant aspects related to functionality and vulnerability within
      bipolar disorder, and for the development of novel treatment interventions.
      Bipolar disorder (BD) is a severe psychiatric illness that has been ranked as one
      of the 20 leading medical causes of disability (WHO, 2011). BD has been shown to
      be the psychiatric disorder with the highest rates of completed suicide across
      two major cohort studies (Ilgen et al., 2010; Nordentoft, Mortensen, & Pedersen,
      2011). In a cross-national representative sample, one in four persons diagnosed
      with bipolar I disorder reported a suicide attempt (Merikangas et al., 2011).
      Rates of relapse remain high despite available treatments (Gitlin, Swendsen,
      Heller, & Hammen, 1995), and in the year after hospitalization for manic episode,
      two-thirds of patients do not return to work (Strakowski et al., 1998). Poverty,
      homelessness, and incarceration are all too common (Copeland et al., 2009).
      Despite the often poor outcomes, there is also evidence for outstanding
      accomplishments and creativity among those with milder forms of the disorder and
      their family members (Coryell et al., 1989; Jamison, 1993; Murray & Johnson,
      2010). Some individuals appear to achieve more than the general population,
      suggesting the importance of understanding the variables that predict
      differential outcome within bipolar disorder. Within this paper, we focus on two
      key predictors of outcomes within bipolar disorder: cognition and emotionality.
      We review evidence that problems in cognition and emotionality are prominent
      among those diagnosed with the disorder, are not artifacts of symptom state, and
      relate substantively to poorer outcomes. Although traditionally studied
      separately, new work points toward the idea that cognition and emotionality are
      intricately linked within bipolar disorder. Drawing from research within bipolar
      disorder as well as outside of bipolar disorder, we build a model of how
      cognition and emotionality might be tied within bipolar disorder. We then provide
      suggestions for future research. Before considering findings, it is worth noting
      that there are several forms of the disorder, defined by varying degrees and
      duration of manic symptoms (APA, 2013; WHO, 1993). Manic episodes are defined by
      abnormally elevated or irritable mood, accompanied by increased activity and at
      least three symptoms (four if mood is only irritable) such as decreased need for
      sleep, increased self-confidence, racing thoughts or flight of ideas, rapid
      speech, distractibility, goal-directed activity, and engagement in pleasurable
      activities without regard to potential negative consequences. To meet criteria
      for mania, these symptoms must persist for at least one week or require
      hospitalization, and must lead to difficulties with functioning. If functional
      impairment is not more than mild and duration is between 4 and 6 days, the
      episode is considered a hypomanic episode. Bipolar I disorder (BD I) is diagnosed
      on the basis of at least one lifetime manic episode within the DSM-5 and by at
      least two episodes within the ICD, whereas bipolar II disorder is diagnosed on
      the basis of at least one hypomanic episode (and no manic episodes) as well as
      major depressive episodes. Cyclothymic disorder is defined by chronic but milder
      fluctuations between manic and depressive symptoms. Most research focuses on BD
      I. In addition to diagnosed samples, research has focused on those at high risk
      for bipolar disorder, including first-degree relatives of those with BD. This
      work draws on the evidence for extremely high heritability of BD I, with
      estimates from community-based twin studies of 0.85 (Kieseppa, Partonen, Haukka,
      Kaprio, & Lonnqvist, 2014). Other research has considered high risk for BD by
      virtue of lifetime subsyndromal symptoms, as measured by scales such as the
      Hypomanic Personality Scale (Eckblad & Chapman, 1986) or the General Behavior
      Inventory (Depue, Krauss, Spoont, & Arbisi, 1989). The study of high-risk
      individuals provides a way to decipher whether deficits are present before the
      onset of the disorder, of importance given models suggesting that episodes of the
      disorder may change brain function (Chang, Steiner, & Ketter, 2000; Strakowski,
      2012) as well as individuals' perceptions of their emotion regulation. Beyond
      defining BD, it is worth defining some of the many different neuropsychological
      tasks that have been widely studied in BD. Perhaps no area has received more
      attention than executive function. Executive function is related to three core
      functions: 1) inhibition, the ability to suppress irrelevant information in
      working memory in order to accomplish an established goal; 2) working memory, the
      ability to hold and manipulate information in mind; and 3) cognitive flexibility,
      the ability to shift strategies in response to feedback (Diamond, 2013; Miyake et
      al., 2000). Attention (defined as the process of selecting information reception
      from internal or external cues) is implicated in all three of these aspects of
      executive function. Much of the literature we will discuss focuses on response
      inhibition, or the ability to suppress a prepotent response, which is considered
      a subtype of inhibition. Some tests measure multiple facets of executive
      function; for example the Trails B test likely requires working memory and
      cognitive flexibility (Sanchez-Cubillo et al., 2009). Aside from executive
      function, multiple other facets of cognition have been widely studied in bipolar
      disorder. Verbal and non-verbal memory are related to the ability to register,
      store and retrieve verbal or visual information (Lezak, 1995). Verbal fluency is
      measured as the number of verbal responses a person can generate to a given
      target, such as a specific semantic category (e.g., animals, furniture) or
      phonetic category (e.g., words that begin with letter F) (Diamond, 2013).
      Although cognitive tasks have been designed to evaluate these specific functions,
      it is important to note that most measures are highly inter-correlated and may
      assess multiple overlapping functions to some extent (for example, the Trails B
      test is often described as an "executive function" task, although this task
      likely involves both working memory and cognitive flexibility. Not surprisingly,
      then, some authors label the function of certain tests differently, and this is
      particularly evident in meta-analyses of cognition. As we describe findings in
      this paper, we will use the terms proposed by the authors but will also identify
      key tests used to define a cognitive construct. With this background in mind, we
      turn to a discussion of cognitive deficits, then of emotion-related traits. Our
      hope is that those concise summaries provide evidence for the importance of both
      domains, but also specificity regarding the facets of emotion and cognition that
      are most impaired in BD. This specificity then guides our consideration of models
      that integrate cognition and emotion.

PMID- 29195775
TI  - Re: Follow-up of Prostatectomy Versus Observation for Early Prostate Cancer.

PMID- 29195774
TI  - Paving TRAIL's Path with Ubiquitin.
AB  - Despite its name, signalling induced by the tumour necrosis factor (TNF)-related
      apoptosis-inducing ligand (TRAIL) is versatile. Besides eliciting cell death by
      both apoptosis and necroptosis, TRAIL can also induce migration, proliferation,
      and cytokine production in cancerous and non-cancerous cells. Unravelling the
      mechanisms regulating the intricate balance between these different outputs could
      therefore facilitate our understanding of the role of TRAIL in tissue
      homeostasis, immunity, and cancer. Ubiquitination and its reversal,
      deubiquitination, are crucial modulators of immune receptor signalling. This
      review discusses recent progress on the orchestration of TRAIL signalling
      outcomes by ubiquitination of various components of the signalling complexes, our
      understanding of the molecular switches that decide between cell death and gene
      activation, and what remains to be discovered.

PMID- 29195776
TI  - Diagnostic Pathways for Screen-detected Prostate Cancer: The Plot Thickens.

PMID- 29195777
TI  - Multiparametric Magnetic Resonance Imaging Is an Independent Predictor of Salvage
      Radiotherapy Outcomes After Radical Prostatectomy.
AB  - BACKGROUND: The Stephenson nomogram is widely used to estimate the success of
      salvage radiotherapy (sXRT) for prostate cancer (PCa) recurrence after radical
      prostatectomy (RP). OBJECTIVE: To determine whether multiparametric pelvic
      magnetic resonance imaging (mpMRI) performed for biochemical recurrence after RP
      improves prognostication of sXRT relative to the Stephenson nomogram. DESIGN,
      SETTING, AND PARTICIPANTS: Men undergoing RP at our institution from 2003 to 2012
      who had biochemical recurrence evaluated by mpMRI within 12 mo of sXRT were
      retrospectively reviewed. Exclusion criteria included PCa treatment prior to RP,
      adjuvant XRT after RP, salvage cryotherapy before sXRT, and hormone refractory
      disease prior to sXRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Multivariable Cox regression analyses (adjusting for Stephenson nomogram
      covariates) associated mpMRI findings with prostate-specific antigen (PSA)
      recurrence and metastasis after sXRT. The mpMR images were compared in a binary
      fashion: no lesion versus vesicourethral/seminal vesical bed/prostate fossa
      lesions. RESULTS AND LIMITATIONS: Among 473 sXRT patients, 57%(204) had lesions
      on mpMRI: 26%(124) vesicourethral, 28%(135) seminal vesical bed/prostatic fossa,
      7%(34) nodal, and 1%(3) bone. Median PSA at mpMRI with lesions was 0.46 versus
      0.40ng/ml without lesions. After excluding nodal/bone lesions, 29% of men
      developed PSA recurrence and 14% metastasis (median follow-up 45 mo after sXRT).
      For patients with a pre-sXRT PSA of <=0.5ng/ml, negative mpMRI was associated
      with increased PSA recurrence (39% vs 12%, p<0.01) and metastasis (16% vs 2%,
      p<0.01) at 4 yr after sXRT. For patients with a PSA of <=0.5ng/ml, the addition
      of mpMRI to the propensity score (created using variables from the original
      Stephenson nomogram) improved the c-statistic from 0.71 to 0.77 for PSA
      recurrence (hazard ratio [HR] 3.60, p<0.01) and from 0.66 to 0.77 for metastasis
      (HR 6.68, p<0.01). Limitations include evolutions in MRI technique and lack of a
      cohort of men undergoing mpMRI electing against sXRT. CONCLUSIONS: Pre-sXRT mpMRI
      improves clinicopathologic variables to estimate sXRT success, particularly in
      the early sXRT setting. PATIENT SUMMARY: Men who have biochemically recurrent
      prostate cancer after radical prostatectomy often receive salvage radiotherapy.
      In our study, multiparametric pelvic magnetic resonance imaging prior to salvage
      radiotherapy was a significant predictor of prostate-specific antigen failure and
      metastasis after radiotherapy.

PMID- 29195778
TI  - Epidemiology and risk factors for Clostridium difficile-associated diarrhea in
      adult inpatients in a university hospital in China.
AB  - BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is an important
      disease with rising incidence and mortality in western countries. However,
      studies about CDAD in China are limited. The aims of this study are to
      investigate the epidemiology and risk factors of CDAD in a university hospital
      located in Eastern China. METHODS: Diarrhea samples of all adult inpatients were
      collected for C difficile culture prospectively from August 2013-April 2014.
      Suspected colonies were identified by biochemical identification cards. Confirmed
      C difficile isolates were further analyzed for the presence of toxin genes and
      typed by polymerase chain reaction ribotyping. Patient demographics, presumed
      risk factors, clinical manifestations, and laboratory findings were collected
      through inpatient medical record systems retrospectively. RESULTS: In total, 45
      stains of toxigenic C difficile were isolated from 315 nonrepetitive diarrhea
      samples. The isolation rate was 14.29% (45/315). No RT027/ST1 strain was found.
      An outbreak of CDAD occurred in the digestive ward and was finally found to be
      caused by ST35 strains during this study. Coloclysis and diabetes were found to
      be independent risk factors of CDAD, besides the common risk factors previously
      reported. CONCLUSIONS: CDAD is not uncommon in Chinese hospitals. C difficile
      ST35 as a new strain causing outbreaks should be noticed. Coloclysis and diabetes
      are new independent risk factors for CDAD, and further study is needed.

PMID- 29195779
TI  - Implementation of remote video auditing with feedback and compliance for manual
      cleaning protocols of endoscopic retrograde cholangiopancreatography endoscopes.
AB  - A pilot initiative to assess the use of remote video auditing in monitoring
      compliance with manual-cleaning protocols for endoscopic retrograde
      cholangiopancreatography (ERCP) endoscopes was performed. Compliance with manual
      cleaning steps following the initiation of feedback was measured. A video feed of
      the ERCP reprocessing room was provided to remote auditors who scored items of an
      ERCP endoscope manual-cleaning checklist. Compliance feedback was provided in the
      form of reports and reeducation. Outcomes were reported as checklist compliance.
      The use of remote video auditing to document manual processing is a feasible
      approach and feedback and reeducation increased manual-cleaning compliance from
      53.1% (95% confidence interval, 34.7-71.6) to 98.9% (95.0% confidence interval,
      98.1-99.6).

PMID- 29195780
TI  - Waterborne Pseudomonas aeruginosa transmission in a hematology unit?
AB  - BACKGROUND: Pseudomonas aeruginosa is an important nosocomial pathogen that
      commonly colonizes hospital water supplies, including in taps and sinks. We
      report the transmission of P. aeruginosa from water to patients in a clinical
      hematology setting. METHODS: P. aeruginosa from water samples were compared to
      clinical isolates from hematology ward patients, via molecular typing (pulsed
      field gel electrophoresis). RESULTS: P. aeruginosa cultured from blood cultures
      from 3 patients was indistinguishable from water strains, by molecular typing.
      Based on infection control inspections, the transmission event was surmised to be
      due to cleaning of equipment, specifically an infusion therapy procedure tray
      used to transport intravenous drugs to patients, with water from an outlet
      colonized by P. aeruginosa. CONCLUSION: We show the importance of holistic
      factors, such as disposal of patient waste water, cleaning of tap outlets, and
      cleaning of medical equipment, in the transmission of P. aeruginosa, and
      demonstrate that the role of waterborne transmission of this organism in a
      hematology setting cannot be overlooked. We suggest that appropriate management
      of water, including both holistic and engineering interventions, is needed to
      stop transmission of P. aeruginosa from water to patients.

PMID- 29195781
TI  - Effect of hand hygiene on infectious diseases in the office workplace: A
      systematic review.
AB  - BACKGROUND: Extensive data suggests that hand hygiene is a critical intervention
      for reducing infectious disease transmission in the clinical setting. However, it
      is unclear whether hand hygiene is effective at cutting down on infectious
      illnesses in non-clinical workplaces. The aim of this review is to assess the
      current literature concerning the effects of hand-washing interventions on
      infectious disease prevention among employees in nonclinical, office-based
      workplaces. METHODS: In compiling this review, PubMed, Scopus, and Business
      Source Premier were examined for studies published from 1960 through 2016.
      RESULTS: Eleven studies (eight experimental, two observational, one a simulation)
      were identified as eligible for inclusion. Hand-hygiene interventions at various
      levels of rigor were shown to reduce self-reported illness symptoms. CONCLUSIONS:
      Hand hygiene is thought to be more effective against gastrointestinal illness
      than it is against respiratory illness, but no clear consensus has been reached
      on this point. Minimal hand-hygiene interventions seem to be effective at
      reducing the incidence of employee illness. Along with reducing infections among
      employees, hand-hygiene programs in the workplace may provide additional benefits
      to employers by reducing the number of employee health insurance claims and
      improving employee morale. Future research should use objective measures of hand
      hygiene and illness, and explore economic impacts on employers more fully.

PMID- 29195782
TI  - HMGB1 mediates depressive behavior induced by chronic stress through activating
      the kynurenine pathway.
AB  - Our previous study has reported that the proactive secretion and role of central
      high mobility group box 1 (HMGB1) in lipopolysaccharide-induced depressive
      behavior. Here, the potential mechanism of HMGB1 mediating chronic-stress-induced
      depression through the kynurenine pathway (KP) was further explored both in vivo
      and in vitro. Depression model was established with the 4-week chronic
      unpredictable mild stress (CUMS). Sucrose preference and Barnes maze test were
      performed to reflect depressive behaviors. The ratio of kynurenine
      (KYN)/tryptophan (Trp) represented the enzyme activity of indoleamine-2,3
      dioxygenase (IDO). Gene transcription and protein expression were assayed by real
      time RT-PCR and western-blot or ELISA kit respectively. Along with depressive
      behaviors, HMGB1 concentrations in the hippocampus and serum substantially
      increased post 4-week CUMS exposure. Concurrent with the upregulated HMGB1
      protein, the regulator of translocation of HMGB1, sirtuin 1 (SIRT1) concentration
      in the hippocampus remarkably increased. In addition to HMGB1 and SIRT1, IDO, the
      rate limiting enzyme of KP, was upregulated at the level of mRNA expression and
      enzyme activity in stressed hippocampi and LPS/HMGB1-treated hippocampal slices.
      The gene transcription of kynurenine monooxygenase (KMO) and kynureninase (KYNU)
      in the downstream of KP also increased both in vivo and in vitro. Mice treated
      with ethyl pyruvate (EP), the inhibitor of HMGB1 releasing, were observed with
      lower tendency of developing depressive behaviors and reduced activation of
      enzymes in KP. All of these experiments demonstrate that the role of HMGB1 on the
      induction of depressive behavior is mediated by KP activation.

PMID- 29195783
TI  - Platelet glycoprotein receptor Ib blockade ameliorates experimental cerebral
      ischemia-reperfusion injury by strengthening the blood-brain barrier function and
      anti-thrombo-inflammatory property.
AB  - Blood-brain barrier (BBB) disruption, thrombus formation and immune-mediated
      inflammation are important steps in the pathophysiology of cerebral ischemia
      reperfusion injury but are still inaccessible to therapeutic interventions.
      Recent studies have provided increasing evidence that blocking of platelet
      glycoprotein (GP) receptor Ib might represent a novel target in treating acute
      ischemic stroke. This research was conducted to explore the therapeutic efficacy
      and potential mechanisms of GPIbalpha inhibitor (anfibatide) in a model of brain
      ischemia-reperfusion injury in mice. Male mice underwent 90 min of right middle
      cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. Anfibatide (1,
      2, 4 ug/kg) or tirofiban were administered intravenously 1 h after reperfusion.
      The results showed that anfibatide could significantly reduce infarct volumes,
      increase the number of intact neuronal cells and improve neurobehavioral
      function. Moreover, anfibatide could reduce post ischemic BBB damage by
      attenuating increased paracellular permeability in the ischemia hemisphere
      significantly. Stroke-induced increases in activity and protein expression of
      macrophage-1 antigen (MAC-1) and P-selectin were also reduced by anfibatide
      intervention. Finally, anfibatide exerted antithrombotic effects upon stroke by
      decreased the number of microthrombi formation. This is the first demonstration
      of anfibatide's efficacy in protecting the BBB integrity and decreasing
      neutrophil inflammation response mediated by MAC-1 besides microthrombus
      formation inhibition in the brain during reperfusion. Anfibatide, as a promising
      anti-thrombo-inflammation agent, could be beneficial for the treatment of
      ischemic stroke.

PMID- 29195784
TI  - A novel in silico minigene vaccine based on CD4+ T-helper and B-cell epitopes of
      EG95 isolates for vaccination against cystic echinococcosis.
AB  - EG95 oncospheral antigen plays a crucial role in Echinococcus granulosus
      pathogenicity. Considering the diversity of antigen among different EG95
      isolates, it seems to be an ideal antigen for designing a universal multivalent
      minigene vaccine, so-called multi-epitope vaccine. This is the first in silico
      study to design a construct for the development of global EG95-based hydatid
      vaccine against E. granulosus in intermediate hosts. After antigen sequence
      selection, the three-dimensional structure of EG95 was modeled and multilaterally
      validated. The preliminary parameters for B-cell epitope prediction were
      implemented such as the possible transmembrane helix, signal peptide, post
      translational modifications and allergenicity. The high ranked linear and
      conformational B-cell epitopes derived from several online web-servers (e.g.,
      ElliPro, BepiPred v1.0, BcePred, ABCpred, SVMTrip, IEDB algorithms, SEPPA v2.0
      and Discotope v2.0) were utilized for multiple sequence alignment and then for
      engineering the vaccine construct. T-helper based epitopes were predicted by
      molecular docking between the high frequent ovar class II allele (Ovar-DRB1*1202)
      and hexadecamer fragments of the EG95 protein. Having used the immune-informatics
      tools, we formulated the first EG95-based minigene vaccine based on T-helper
      epitope with high-binding affinity to the ovar MHC allele. This designed
      construct was analyzed for different physicochemical properties. It was also
      codon-optimized for high-level expression in Escherichia coli k12. Taken all, we
      propose the present in silico vaccine constructs as a promising platform for the
      generation of broadly protective vaccines for species and genus-specific
      immunization of the natural hosts of the parasite.

PMID- 29195785
TI  - Chest High-resolution Computed Tomography Findings in 601 Patients with
      Inflammatory Bowel Diseases.
AB  - RATIONALE AND OBJECTIVES: Pulmonary involvement in inflammatory bowel disease may
      reflect the common embryonic origin of the gastrointestinal tract and the
      bronchial tree. No studies have compared pulmonary high-resolution computed
      tomography (HRCT) findings between ulcerative colitis (UC) and Crohn disease
      (CD). This study aimed to assess the relationship between pulmonary HRCT findings
      and inflammatory bowel disease activity and to compare HRCT findings between UC
      and CD. MATERIALS AND METHODS: We retrospectively identified 601 consecutive
      patients (350 with UC and 251 with CD) who had undergone chest HRCT examinations
      at our institutions between April 2004 and April 2016. Parenchymal abnormalities,
      enlarged lymph nodes, and pleural effusion were evaluated on HRCT. RESULTS: One
      hundred sixty-seven patients (94 men, 73 women; aged 12-86 years, mean: 47.2
      years) with UC and 93 patients (61 men, 32 women; aged 12-71 years, mean: 37.9
      years) with CD had abnormal findings on chest HRCT. The HRCT findings of UC and
      CD mainly consisted of centrilobular nodules (in 49.1% and 45.2% of cases,
      respectively) and bronchial wall thickening (in 31.7% and 54.8%, respectively).
      There was no relationship between HRCT findings and disease activity. Bronchial
      wall thickening was significantly more frequent in patients with CD than in those
      with UC (P < .001). CONCLUSION: The main chest HRCT findings in UC and CD are
      centrilobular nodules and bronchial wall thickening. There are differences in
      HRCT findings between UC and CD.

PMID- 29195786
TI  - Normal Axillary Lymph Node Variability Between White and Black Women on Breast
      MRI.
AB  - RATIONALE AND OBJECTIVES: This study aimed to determine if there were differences
      in the imaging features of normal lymph nodes between white and black women using
      magnetic resonance imaging. MATERIALS AND METHODS: Following institutional review
      board approval, we identified white and black women who underwent breast magnetic
      resonance imaging from November 1, 2008 to December 31, 2013 at our institution.
      To identify normal lymph nodes for measurement, patients with any benign or
      malignant causes for lymph node enlargement and patients with any subsequent
      breast cancer in the following 2 years were excluded. Black and white women were
      age matched at a 1:2 ratio. The largest lymph node in each axilla was measured
      for the long-axis length and maximal cortical thickness. Comparisons were made
      between white and black women using a conditional logistic regression to control
      for matching. RESULTS: There were 55 black women and 110 white women for
      analysis. The mean lymph node long-axis length was 14.7 +/- 5.3 mm for black
      women and 14.4 +/- 6.4 mm for white women (P = .678). The mean maximum cortical
      thickness was 3.3 +/- 1.6 mm for black women and 2.6 +/- 1.4 mm for Caucasian
      women (P < .001). A significantly higher percentage of black than white women had
      cortical thicknesses greater than threshold values of 3, 4, 5, 6, and 7 mm (P <
      .01 for all). CONCLUSIONS: The normal lymph node cortical thickness in black
      women is significantly greater than in white women, which should be considered
      when deciding to recommend a lymph node biopsy.

PMID- 29195787
TI  - High-risk Plaque and Calcification Detected by Coronary CT Angiography to Predict
      Future Cardiovascular Events After Percutaneous Coronary Intervention.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to investigate whether
      high-risk plaque (HRP) and calcium assessed by coronary computed tomography (CT)
      could predict future cardiovascular events after second-generation drug-eluting
      stent (DES) placement. MATERIALS AND METHODS: We analyzed 317 patients from
      December 2012 to April 2015 who underwent coronary CT followed by DES placement.
      HRP was defined as a plaque with positive remodeling and low attenuation or a
      plaque with a napkin-ring sign. Coronary calcium was assessed by Agatston score
      (AS). Patients were divided into three groups: low risk, HRP negative and AS
      <400; intermediate risk, HRP positive and AS >=400; high risk, HRP positive and
      AS >=400. The primary end point was a composite of all-cause mortality,
      myocardial infarction, fatal arrhythmia, or repeated revascularization. Kaplan
      Meier analysis was used to estimate the distribution of time to events. RESULTS:
      A total of 74 events (23%) occurred during a median follow-up of 25.8 months.
      Patients with primary end points had HRP more frequently (70% vs 51%, P = 0.003)
      and were more calcified (AS, 471 [interquartile range, 143-1614] vs 289
      [interquartile range, 63-787]; P = 0.01) than patients without primary end
      points. The frequency of primary end point increased significantly in the
      intermediate- and high-risk patients (P = 0.0011). Multivariate analysis showed
      that the hazard ratio of the intermediate- and high-risk groups was 1.91 (95%
      confidence interval, 1.04-3.77; P = 0.037) and 2.66 (95% confidence interval,
      1.27-5.73; P = 0.009), respectively. CONCLUSION: Plaque and calcification
      analysis by coronary CT could predict future cardiovascular events after second
      generation DES placement.

PMID- 29195788
TI  - Transcatheter aortic valve replacement: Suitable for all?

PMID- 29195789
TI  - Responses of PKCepsilon to cardiac overloads on myocardial sympathetic
      innervation and NET expression.
AB  - Protein kinase C (PKC) is a key mediator of many diverse physiological and
      pathological responses. PKC activation play an important regulatory role of
      cardiac function. The present study was performed to investigate whether there
      were differential activations of the PKCepsilon and how the activation coupled
      with norepinephrine transporter (NET) surface expression, sympathetic innervation
      pattern and extracellular matrix remodeling in different cardiac hemodynamic
      overloads induced by abdominal aortic constriction or aortocaval fistula. At
      8weeks after the operations, heart failure were induced, accompanied with
      myocardial hypertrophy, which was more pronounced in pressure overload (POL) than
      that of volume overload (VOL) rats, left ventricular dysfunction and increased
      plasma norepinephrine (NE). In POL rats there was an increase in myocardial
      collagen deposition, in contrast, the amount decreased in VOL as compared with
      the sham rats. POL remarkably upregulated PKCepsilon membrane-cytosol ratio and
      downregulated NET membrane fraction, whereas, in VOL induced opposite changes.
      Accompanied with the PKCepsilon activation, nerve sprouting, evidenced by
      myocardial GAP43 protein increased, and different nerve phenotypes were found, in
      POL tyrosine hydroxylase (TH) positive nerve density increased with NET and
      choline acetyltransferase (ChAT) immunoreactivity density decreased, in contrast,
      in VOL NET and ChAT increased, TH did not change. The overloads did not induce
      alteration of NET mRNA expression, but resulted in different myocardial beta1-AR
      mRNA expression, in POL beta1-AR mRNAwas significantly downregulated, while in
      VOL rats unaltered. Conclusion, the present results suggested that the different
      cardiac hemodynamic overload could differentially activate a common signaling,
      PKCepsilon intermediate and thereby generate biological diversity.

PMID- 29195790
TI  - Myocardial Infarction During Pregnancy; Not Only Coronary Artery Dissections:
      Comment on Rose et al., Pregnancy-Related Spontaneous Coronary Artery Dissection:
      A Case Series and Literature Review.

PMID- 29195791
TI  - Reply to Dr. Lameijer.

PMID- 29195792
TI  - Response to van der Vrande et al.: adenocarcinoma of the gastric pouch after Roux
      en-Y gastric bypass: a new technique for en bloc resection and reconstruction.

PMID- 29195793
TI  - Comment on: qualifying for bariatric surgery: is preoperative weight loss a
      reliable predictor of postoperative weight loss?

PMID- 29195794
TI  - Design, synthesis and pharmacological evaluation of some novel indanone
      derivatives as acetylcholinesterase inhibitors for the management of cognitive
      dysfunction.
AB  - The present study reports the effect of indanone derivatives on scopolamine
      induced deficit cholinergic neurotransmission serving as promising leads for the
      therapeutics of cognitive dysfunction. Eleven compounds 54-64 have been designed,
      synthesised and evaluated against behavioural alterations using step down passive
      avoidance protocol at a dose of 0.5 mg/kg with Donepezil (1) as the reference
      standard. All the synthesised compounds were evaluated for their in vitro
      acetylcholinesterase (AChE) inhibition at five different concentrations using
      mice brain homogenate as the source of the enzyme. Compounds 54, 56, 59 and 64
      displayed appreciable activity with an IC50 value of 14.06 uM, 12.30 uM, 14.06 uM
      and 12.01 uM, respectively towards acetylcholinesterase inhibition. The molecular
      docking study performed to predict the binding mode of the compounds suggested
      that these compounds could bind appreciably to the amino acids present at the
      active site of recombinant human acetylcholinesterase (rhAChE). The behavioural,
      biochemical and in silico pharmacokinetic studies were in concordance with each
      other.

PMID- 29195795
TI  - 7-Methylguanosine monophosphate analogues with 5'-(1,2,3-triazoyl) moiety:
      Synthesis and evaluation as the inhibitors of cNIIIB nucleotidase.
AB  - The hydrolysis of nucleoside 5'-monophosphates to the corresponding nucleosides
      and inorganic phosphate is catalysed by 5'-nucleotidases, thereby contributing to
      the control of endogenous nucleotide turnover and affecting the fate of
      exogenously delivered nucleotide- and nucleoside-derived therapeutics in cells. A
      recently identified nucleotidase cNIIIB shows preference towards 7
      methylguanosine monophosphate (m7GMP) as a substrate, which suggests its
      potential involvement in mRNA degradation. However, the extent of biological
      functions and the significance of cNIIIB remains to be elucidated. Here, we
      synthesised a series of m7GMP analogues carrying a 1,2,3-triazole moiety at the
      5' position as the potential inhibitors of human cNIIIB. The compounds were
      synthesised by using the copper-catalysed azide-alkyne cycloaddition (CuAAC)
      between 5'-azido-5'-deoxy-7-methylguanosine and different phosphate or
      phosphonate derivatives carrying terminal alkyne. The analogues were evaluated as
      cNIIIB inhibitors using HPLC and malachite green assays, demonstrating that
      compound 1a, carrying a 1,2,3-triazoylphosphonate moiety, inhibits cNIIIB
      activity at micromolar concentrations (IC50 87.8 +/- 7.5 uM), while other
      analogues showed no activity. In addition, compound 1d was identified as an
      artifical substrate for HscNIIIB. Further characterization of inhibitor 1a
      revealed that it is poorly recognised by other m7G-binding proteins, eIF4E and
      DcpS, indicating its selectivity towards cNIIIB. The first inhibitor (1a) and
      unnatural substrate (1d) of cNIIIB, identified here, can be used as molecular
      probes for the elucidation of biological roles of cNIIIB, including the
      verification of its proposed function in mRNA metabolism.

PMID- 29195796
TI  - A low gradient junction technique of craniospinal irradiation using volumetric
      modulated arc therapy and its advantages over the conventional therapy.
AB  - A technique using volumetric-modulated arc therapy (VMAT) fields for craniospinal
      irradiation with low dose gradients at the field junction was tested for its
      sensitivity to positional inaccuracy. It was compared against the conventional
      three-dimensional (3D) conformal radiotherapy in terms of dose uniformity at the
      junction. Treatment plans generated for ten patients who received craniospinal
      irradiation (35Gy in 21 fractions) by VMAT technique at our centre were included
      in this study. For these patients, 3D conformal radiotherapy plans were also
      generated in addition to the VMAT treatment plans. Intentional shifting of the
      cranial field in the superior and then in the inferior directions was done,
      creating a gap or overlap between the fields. Consequent changes in dose
      distributions in these two plans to positional inaccuracies were studied. The 3D
      conformal radiotherapy plans showed large dose variations at the junction due to
      positional shifts as compared to the VMAT plans. With a 5mm superior shift of the
      cranial field isocentre creating a gap between the cranial and spinal fields, the
      magnitudes of under-dosing were 13.9+/-3.6Gy and 4.8+/-2.0Gy for 3D conformal
      radiotherapy and VMAT respectively. When the cranial field was moved by 5mm
      inferiorly creating an overlap between the fields, overdose to the effects of
      10.3+/-4.0Gy and 4.9+/-1.3Gy were observed for the 3D conformal radiotherapy
      plans and VMAT plans respectively. The VMAT technique is insensitive to
      longitudinal setup errors (1-3mm) in patients because of the existence of low
      dose gradients at the junction between fields. This is unlike the 3D conformal
      radiotherapy plans which have steep dose gradients at the field edges and thus
      are highly sensitive to setup errors. Such an advantage for VMAT circumvents the
      need for dose feathering often practiced with the 3D conformal radiotherapy
      technique and makes the technique simpler to follow.

PMID- 29195797
TI  - Laparoscopic Ureteroneocystostomy with a Vesicopsoas Hitch in 10 Steps.
AB  - STUDY OBJECTIVE: Laparoscopic ureteroneocystostomy with a vesicopsoas hitch has
      the advantages of a minimally invasive approach. The standardization and
      description of the technique are the main objectives of this video. We described
      this procedure in 10 steps, which could help to understand and perform this
      procedure. METHODS: This video presents an approach to laparoscopic
      ureteroneocystostomy with a vesicopsoas hitch, which was clearly divided into 10
      steps. The local institutional review board was consulted and ruled that approval
      was not required for this video article because the video describes a technique
      and does not report a clinical case. The patient cannot be identified, and she
      gave informed consent. RESULTS: The 10 steps are as follows: step 1,
      identification of the healthy ureter; step 2, identification of the stenotic
      part; step 3, section of the ureter; step 4, bladder mobilization; step 5,
      anterior cystostomy; step 6, psoas hitch; step 7, closure of the anterior
      cystostomy; step 8, posterior spatulation of the ureter; step 9, cystostomy of
      the superolateral bladder dome; and step 10, ureteral suture to the bladder.
      CONCLUSION: Laparoscopic ureteroneocystostomy with a vesicopsoas hitch is an
      effective technique for intrinsic ureteral endometriosis; it usually needs
      ureteral resection with end-to-end reanastomosis or reimplantation if the
      anastomosis is in tension. The 10 steps help to perform each part of surgery in
      logical sequence, making the procedure faster to adopt and learn. The
      standardization of laparoscopic techniques could help to reduce the learning
      curve.

PMID- 29195798
TI  - Transarterial Embolization of a Bartholin Cyst before Resection.

PMID- 29195799
TI  - Fabrication of carboxylated cellulose nanocrystal/sodium alginate hydrogel beads
      for adsorption of Pb(II) from aqueous solution.
AB  - Carboxylated cellulose nanocrystal-sodium alginate (CCN-Alg) hydrogel beads were
      easily prepared through a cross-linking method. The structure and properties of
      the composite beads were characterized by TEM, FTIR, SEM, XPS, thermogravimetric
      analysis (TGA), and zeta potential measurement. A high ratio of 76% of the Pb(II)
      ion was adsorbed within the first 2h, and the adsorption equilibrium was nearly
      reached after 3h. The experimental isotherm could be fitted by the Langmuir
      model, yielding an extreme adsorption capacity of 338.98mgg-1. The adsorption
      process followed a pseudo-second-order kinetic model, and thermodynamic analyses
      confirmed that the adsorption is a spontaneous and endothermic process.
      Regeneration tests with acid treatment indicated that the CCN-Alg beads performed
      well in repeated Pb(II) adsorptions, as they could maintain an adsorption
      capacity of 223.2mgg-1 after five repeated cycles. These results indicate that
      these CCN-Alg beads are a potentially effective and sustainable adsorbent for
      application in wastewater treatment.

PMID- 29195800
TI  - NIR triggered liposome gold nanoparticles entrapping curcumin as in situ adjuvant
      for photothermal treatment of skin cancer.
AB  - We report the synthesis of a biodegradable liposome gold nanoparticles for
      curcumin (Au-Lipos Cur NPs) delivery. This entrapped curcumin served as an in
      situ adjuvant for photothermal therapy. Curcumin was loaded in Au-Lipos NPs with
      an encapsulation efficiency of ~70%. The gold coating enabled the NPs to
      specifically absorb NIR light (780nm) by virtue of Surface Plasmon Resonance
      (SPR) and this light energy was converted to heat. The generated heat
      destabilized the liposomal core enhancing the release of encapsulated curcumin.
      Photothermal transduction efficacy of Au-Lipos NPs (loaded with curcumin) showed
      a significant temperature rise upon laser irradiation causing irreversible
      cellular damage. In vitro photothermal effect and intracellular uptake was
      evaluated in B16 F10 (melanoma) cell line. Au-Lipos Cur NPs showed significantly
      enhanced uptake when compared with free curcumin. Enhancement in cancer cell
      cytotoxicity was observed in Au-Lipos Cur NPs treated group upon laser
      irradiation owing to curcumin. Our findings indicate that curcumin could serve as
      a potential in situ adjuvant for photothermal therapy of melanoma.

PMID- 29195802
TI  - Comments on prediction of lymph node metastasis in pancreatic neuroendocrine
      tumors by contrast enhancement characteristics.

PMID- 29195801
TI  - Discovery of potent and reversible MAO-B inhibitors as furanochalcones.
AB  - A series of twelve furanochalcones (F1-F12) was synthesized and investigated for
      their human monoamine oxidase inhibitory activities. Among the series, compound
      (2E, 4E)-1-(furan-2-yl)-5-phenylpenta-2, 4-dien-1-one (F1), which was analyzed by
      single-crystal X-ray diffraction, showed potent and selective MAO-B inhibitory
      activity with an inhibition constant (Ki) value of 0.0041 MUM and selectivity
      index of (SI) 172.4, and exhibited competitive inhibition. Introduction of a
      cinnamyl group to the furanochalcone significantly increased the inhibitory
      activity. In the dilution-recovery experiments, the residual activities of MAO-A
      and MAO-B by F1 under the diluted condition fully recovered as compared with the
      undiluted condition, indicating F1 is a reversible inhibitor. The Ki value of F1
      is the lowest among the values of chalcone derivatives and furthermore lower than
      that (0.0079 MUM) of the reversible MAO-B inhibitor, lazabemide, a marketed drug.
      Molecular docking study against hMAO-B provided the binding site interactions of
      the lead compound, including strong pi-pi stacking between the phenyl system and
      FAD nucleus.

PMID- 29195803
TI  - [Validation of the French version of the self-evaluation of negative symptoms
      (SNS)].
AB  - INTRODUCTION: Schizophrenia is a disorder affecting 1% of the population and is
      associated with severe functional impairment. Negative symptoms are responsible
      for the majority of this impairment, and many patients with schizophrenia have
      negative symptoms. However, their evaluation is still a challenge. Thus,
      standardized assessments are needed to facilitate identification of these
      symptoms. Many tools have been developed, but most are based on observer ratings.
      Self-evaluation can provide an additional outcome measure and allow patients to
      be more engaged in their treatment. The Self-evaluation of Negative Symptoms
      (SNS) has been developed recently. This is a remarkably understandable instrument
      for patients with schizophrenia as it allows them to readily complete it without
      assistance, providing information with respect to their own perception of
      negative symptoms. The SNS is a self-assessment that permits patients to evaluate
      themselves in 5 dimensions of negative symptoms. This validation study for the
      SNS revealed good psychometric properties alongside satisfactory acceptance by
      patients. AIM: This study was to confirm the validation of the French version of
      the self-evaluation of negative symptoms (SNS). METHODS: Patients with
      schizophrenia or schizoaffective disorder according to the DSM-IV-R, with a
      stable regimen of anti-psychotic drugs for the last two months, aged more than 18
      years old were eligible for the study. Symptoms were rated using the SNS, the
      Scale for the Assessment of Negative Symptoms (SANS), the Calgary Depression
      Scale for Schizophrenics (CDSS), the Brief Psychiatric Rating Scale (BPRS) and
      the Clinical Global Impression and Parkinsonism. Patients were asked to fulfill
      the SNS twice, 6 weeks apart. RESULTS: Sixty patients were evaluated. Cronbach's
      coefficient (alpha=0.8) showed good internal consistency. The SNS significantly
      correlated with the SANS (r=0.6), the negative sub-score of the BPRS (r=0.6) and
      the Clinician Global Impression on the severity of negative symptoms (r=0.7). SNS
      scores did not correlate with level of insight (r=0.08) or Brief Psychiatric
      Rating Scale positive sub-scores (r=0.2). SNS scores correlated with CDSS scores.
      However, we did not find correlation between the first item of the CDSS which
      evaluates depression and the "diminished emotional range" sub-score of SNS. The
      test-retest of SNS revealed no changes of scores at two evaluations 6 weeks
      apart. CONCLUSION: The acceptance by patients of the SNS was excellent. The
      French version of the SNS demonstrated a good internal consistency, good
      convergent validity and good discriminant validity. The study demonstrates the
      ability of patients with schizophrenia to accurately report their own
      experiences. Self-assessments of negative symptoms should be more widely employed
      in clinical practice because they may allow patients with schizophrenia to
      develop appropriate coping strategies.

PMID- 29195804
TI  - [Psychostimulants for late life depression].
AB  - OBJECTIVES: The use of psychostimulants in the treatment of depressive disorders
      is receiving renewed interest. Recent publications suggest a particular interest
      of psychostimulants in the treatment of depression in the elderly. The aim of
      this article is to review the literature on the role of psychostimulants in the
      treatment of depression in older adults. METHODS: The literature review focused
      on efficacy and tolerability studies of psychostimulants in the treatment of
      depression for the elderly that were published between 1980 and 2016. The only
      inclusion criterion applied was an average age of the sample studied greater than
      or equal to 60 years. RESULTS: Overall, 12 trials were selected: 3 controlled
      trials and 9 uncontrolled trials. Of the 3 controlled trials, one compared
      parallel groups and the other two were cross-tests. Among the psychostimulants,
      methylphenidate was the most studied molecule. The trials demonstrate an efficacy
      of this molecule in particular as an add-on therapy in old-age depression but for
      the most part with a level of proof that remains insufficient. CONCLUSIONS: The
      small size of the samples and the methodological limitations of the studies
      obviate the possibility of extracting definitive conclusions concerning the place
      of psychostimulants in the treatment of depression in the elderly. Further
      studies are required in particular in the treatment of resistant depressive
      episodes.

PMID- 29195805
TI  - [Symptomatic remission and its relationship to social functioning in Tunisian out
      patients with schizophrenia].
AB  - INTRODUCTION: The concept of symptomatic and functional remission represents an
      important challenge in the care of the mentally ill, particularly in patients
      with schizophrenia. Operational criteria for symptomatic remission in
      schizophrenia have been proposed by Andreasen et al. (2005). Over the last
      decade, these criteria have been widely validated; however few studies have been
      conducted outside developed countries. Moreover, the association of symptomatic
      remission with functional outcome has not yet been established in developing
      countries including Tunisia, as there may be variability in the social and
      familial environment. OBJECTIVES: To determine the frequency and associated
      factors of symptomatic remission in a sample of Tunisian out-patients with
      schizophrenia and to explore the relationship between symptomatic remission and
      some indicators of social functioning. METHODS: A cross-sectional study was
      carried-out on 115 out-patients with schizophrenia (87 males, 28 females, mean
      age=37.56+/-10.2 years) in the psychiatry department of the university hospital
      in Monastir (Tunisia). Nearly all of the patients (98.26%) had been hospitalized
      at least once in a psychiatric unit. The last hospitalization dated back to 39
      months on average (range=6 months to 16 years). Symptomatic remission was
      assessed by the eight core items of the positive and negative syndrome scale
      (PANSS). These are the items P1 "Delusions"; P3 "Hallucinatory behavior" and G9
      "Unusual thought content" for the positive dimension, the items P2 "Conceptual
      disorganization" and G5 "Mannerism and disorders of posture" for the
      disorganization dimension and the items N1 "Blunted affect", N4 "Social
      withdrawal" and N6 "Lack of spontaneity and flow of conversation" for the
      negative dimension. A score of mild or less on all eight-core symptoms
      constitutes symptomatic remission. This symptom level should have been maintained
      for six months. The social functioning was assessed by the Social and
      Occupational Functioning Assessment Scale (SOFAS) and the Social Autonomy Scale
      (SAS) exploring personal care, management of daily life, resource management, the
      relationship with the outside and the emotional life and relationships social. A
      multivariate analysis using a binary logistic regression was conducted with as a
      dependent variable "symptomatic remission" and as explanatory variables the
      associated variables with symptomatic remission in bivariate analysis with age
      and gender. RESULTS: The symptomatic remission was observed in 50.4% of patients.
      The items corresponding to positive dimension (P1, P3 and G9) and the item P2
      "conceptual disorganization" had a better predictive value of symptomatic
      remission. After multivariate analysis, the associated factors of symptomatic
      remission were the acute of onset (P=0.026), the low score of negative symptoms
      during the last hospitalization (P=0.017) and the episodic course (P<0.0001).
      However, age or gender of the patients, educational or socioeconomic level,
      psychiatric family history, age of onset, duration of untreated psychosis, number
      and duration of previous hospitalizations, antipsychotic treatment dosage were
      not associated with symptomatic remission in our sample. The mean score of the
      SOFAS was 48.47+/-14.44, and the mean score of the SAS was 56.6+/-16.84. A
      significant association was shown between the SOFAS score and the symptomatic
      remission (P<0.0001) and between the SAS score and the symptomatic remission
      (P<0.0001). Moreover, a significant association was found between symptomatic
      remission and occupational activity (P=0.03). CONCLUSION: The frequency of
      symptomatic remission according the PANSS criteria in our sample is above the
      average of the reported rates in literature (30 to 60%). This can be explained by
      the frequency of symptomatic remission in outpatient versus inpatients, or in
      relation to the notion of a more favorable course of schizophrenia in developing
      countries, although this notion is controversial. Remitter patients had
      significantly an acute onset of disorders, a low score of negative symptoms
      during the last hospitalization and an episodic course. They also showed a
      significant trend for better social functioning. In fact, a significant
      association was shown in our sample between symptomatic remission and social
      functioning. These results suggest that the concept of remission has important
      implications for the treatment of patients with schizophrenia.

PMID- 29195806
TI  - [Evolution of suicide attempts in a Tunisian clinical population between 2005 and
      2015: New modalities for young people to commit suicide?]
AB  - INTRODUCTION: Suicide and suicide attempts represent a worldwide health priority.
      The aim of our study was to describe the epidemiological and clinical
      characteristics of young suicide attempters among a clinical population and to
      assess their potential evolution over a period of11 years. METHODS: We conducted
      a descriptive retrospective study among a clinical population of suicide
      attempters referred to the child psychiatric department of the Razi hospital, the
      inpatient reference department in the north and center of Tunisia, between
      January 2005 and December 2015. Based on the WHO definition we considered as
      suicide attempts, "any deliberate act, without any fatal outcome, aimed at
      performing a gesture of violence on one's own person or to ingest a toxic
      substance or drugs at a dose higher than the dose recognized as therapeutic". We
      conducted collection of data from patient records based on a pre-established
      record with the following parameters: clinical study of patients including: socio
      demographic data, clinical characteristics based on DSM 4 criteria and
      environmental factors including family history of psychiatric disorder, abuse,
      school difficulties and failure. RESULTS: The sample was composed of 159 patients
      having a mean age of 12.8 years with extremes from 5.8 to 17 years. It was
      composed of 74.2% girls and 25.8% boys. Medical intoxication was the most common
      mean (68.6%) followed by physical means (20.1%) and toxic products ingestion
      (12.6%). The suicide attempts were mainly non-premeditated (83.1%). Our patients
      reported a previous suicide attempt in 25.8% of cases. Chronic somatic disorders
      were found among 24.5% of our sample. Psychiatric disorders among children,
      parents, abuse, and school failure were found in respectively 48.4%, 50.6%, 37.1%
      and 13.4% of suicidal patients. Psychiatric disorders were dominated by
      depressive disorders and oppositional defiant disorders associated with conduct
      disorder. The chronological study highlighted significant modifications starting
      from 2013/2014, reflecting a recent trend: a significant decrease in suicidal age
      was found since the year 2015: children under 10 years of age, who constituted
      8.4 % (n=10) of suicides during the period from (n=119), accounted for 20 %
      (n=32) of the patients enumerated in the year 2015 (P=0.045). We also found that
      the percentage of suicidal attempts committed in winter was higher from 2013 than
      in previous years (P=0.019). We also noted a significant increase in 2014 in the
      proportion of patients with a personal history of suicidal attempt when compared
      to previous years (P=0.045). The use of physical means became more frequent from
      2013 (P=0.019). This is confirmed by comparing the suicide attempts prior to and
      from 2014 (P=0.007) or by comparing the suiced attempts committed in 2015 to the
      ones committed during the previous ten years (P=0.007). Finally, there was a
      statistically significant distribution of serious organic effects (coma) as a
      function of years: such complications were more frequent in the course of
      suicidal attempts committed after 2013 (P=0.009). CONCLUSIONS: Since 2013/2014 we
      found a recent trend characterized by more children among suicidals, more
      patients reporting a previous suicide attempt, more frequent use of physical
      means and a greater proportion of suicide attempts realized in winter. This
      raises the challenge for more research on the topic as well as new therapeutic
      interventions.

PMID- 29195807
TI  - Parallel Evaluation of Circulating Tumor DNA and Circulating Tumor Cells in
      Metastatic Colorectal Cancer.
AB  - BACKGROUND: Tissue biopsy is the gold standard for tumor genotyping, but it is an
      invasive procedure providing a single snapshot into tumor heterogeneity. Liquid
      biopsy approaches, encompassing the analysis of circulating tumor DNA (ctDNA) or
      circulating tumor cells (CTCs), have been proposed as an alternative, with the
      potential of providing a comprehensive portrait of the tumor molecular landscape.
      In metastatic colorectal cancer (mCRC), both CTCs and ctDNA analysis have been
      investigated, but comparative analyses are limited. METHODS: We collected blood
      samples from 20 consecutive patients with mCRC with at least 1 of the following
      inclusion criteria: high tumor burden (> 1 metastasis), intact colonic primary
      tumor, disease progression at the time of sampling, <= 2 cycles of cytotoxic
      chemotherapy of current treatment course, and time between last chemotherapy
      cycle >= 4 weeks. RESULTS: Nineteen of 20 samples displayed the appropriate
      quality for CTC analysis. CTCs could be isolated in 7 (36.8%) of 19 evaluable
      patients. The median number of CTCs was 0 (range, 0-73). In 2 patients, we
      isolated > 1 CTC, and in five, we found 1 CTC. We retrieved ctDNA in all samples,
      with a median amount of 732,573 GE/mL (range, 174,774-174,078,615 GE/mL).
      Concordance between ctDNA and tissue for RAS, BRAF, and ERBB2 alterations was
      found in 11 (84.6%) of 13 cases. CONCLUSIONS: In this cohort, we show that ctDNA
      was detectable in all cases, whereas CTCs were detectable in one-third of the
      cases. ctDNA analysis was achieved with a smaller amount of blood sampling and
      allowed molecular characterization. Our data indicate that ctDNA is a readily
      available candidate for clinical application in mCRC.

PMID- 29195808
TI  - Excellent prognosis of patients with intermediate-risk neuroblastoma and residual
      tumor postchemotherapy.
AB  - BACKGROUND/PURPOSE: The prognosis of patients with intermediate-risk
      neuroblastoma is favorable; therefore, a reduction therapy is desired. However,
      the long-term prognosis of those with residual tumor is unclear. The aim of this
      study was to clarify the necessity of residual tumor resection. METHODS: We
      retrospectively reviewed the records of patients diagnosed with intermediate-risk
      neuroblastoma who either were treated by chemotherapy only (nonresection group;
      n=16), or received postchemotherapy tumor resection (resection group; n=9).
      RESULTS: In the nonresection group, tumor size decreased in 14 patients; 5 had no
      detectable local tumor at the end of the follow-up period. Tumor size increased
      in 2 patients 1.5-2.5years postchemotherapy. Both patients received additional
      treatment and survived. All patients survived during the median follow-up time of
      127months. In the resection group, 5 patients received complete resections and 4
      patients received nearly complete resections. All patients survived during the
      median follow-up time of 84months. In 8 out of 9 resected tumors, regression or
      maturation was pathologically induced by chemotherapy-only treatment. CONCLUSION:
      Patients with intermediate-risk neuroblastoma with or without postchemotherapy
      residual tumor resection had an excellent long-term outcome. The tumor pathology
      with intermediate-risk neuroblastoma might be susceptible to change to regression
      or maturation by chemotherapy. LEVEL OF EVIDENCE: IV.

PMID- 29195809
TI  - Reduced psychological distress in familial chylomicronemia syndrome after patient
      support group intervention.
AB  - Familial chylomicronemia syndrome (FCS) is a rare genetic disorder that is
      associated with severe hypertriglyceridemia and complications that often include
      recurrent pancreatitis beginning in childhood. Patients with FCS frequently
      struggle to maintain normality in their lives as a consequence of the necessity
      to severely restrict their intake of dietary fat coupled with the constant threat
      of recurrent pancreatitis. Patients typically face a high level of psychological
      stress and anxiety in association with reduced measures of quality of life.
      Routine medical care for affected patients usually does not adequately address
      the day-to-day struggles that accompany a diagnosis of FCS, resulting in ongoing
      suffering for many patients. We describe herein the highly beneficial effects of
      a support group interaction for a patient with FCS.

PMID- 29195811
TI  - The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from
      Living Macrophages.
AB  - The interleukin-1 (IL-1) family cytokines are cytosolic proteins that exhibit
      inflammatory activity upon release into the extracellular space. These factors
      are released following various cell death processes, with pyroptosis being a
      common mechanism. Recently, it was recognized that phagocytes can achieve a state
      of hyperactivation, which is defined by their ability to secrete IL-1 while
      retaining viability, yet it is unclear how IL-1 can be secreted from living
      cells. Herein, we report that the pyroptosis regulator gasdermin D (GSDMD) was
      necessary for IL-1beta secretion from living macrophages that have been exposed
      to inflammasome activators, such as bacteria and their products or host-derived
      oxidized lipids. Cell- and liposome-based assays demonstrated that GSDMD pores
      were required for IL-1beta transport across an intact lipid bilayer. These
      findings identify a non-pyroptotic function for GSDMD, and raise the possibility
      that GSDMD pores represent conduits for the secretion of cytosolic cytokines
      under conditions of cell hyperactivation.

PMID- 29195812
TI  - Effects of a single condylar neck fracture without condylar cartilage injury on
      traumatic heterotopic ossification around the temporomandibular joint in mice.
AB  - OBJECTIVES: In this study, we tried to explore the effects of a single condylar
      neck fracture without condylar cartilage injury during the pathogenesis process
      of traumatic heterotopic ossification around the temporomandibular joint (THO
      TMJ). STUDY DESIGN: One-month-old C57 BL/6 J male mice were divided into 2
      groups. In group 1, condylar cartilage was partially removed in the right joint
      to induce THO. In group 2, a single fracture on the condylar neck was created
      using small scissors. The condylar head was repositioned to its original place if
      any displacement occurred. The phenotypes were observed using gross observation,
      micro-computed tomography, and histologic examination. RESULTS: The results
      showed obvious hyperplasia in the right condyle in group 1, with ectopic bones
      and cartilage in the periarticular region. In group 2, the surface of condyle was
      smooth, but the size of the right condylar head became smaller. CONCLUSIONS:
      Taking these findings together, we concluded that it is condylar cartilage
      injury, and not a single condylar neck fracture without condylar cartilage
      injury, that contributes to the development of THO-TMJ.

PMID- 29195813
TI  - Clinical pathologic conference: diffuse papillomatous lesions of the gingiva with
      posterolateral neck skin tags.

PMID- 29195810
TI  - Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies.
AB  - Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major
      surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from
      malaria in animal models but protective humoral immunity is difficult to induce
      in humans. Here we cloned and characterized rare affinity-matured human NANP
      reactive memory B cell antibodies elicited by natural Pf exposure that potently
      inhibited parasite transmission and development in vivo. We unveiled the
      molecular details of antibody binding to two distinct protective epitopes within
      the NANP repeat. NANP repeat recognition was largely mediated by germline encoded
      and immunoglobulin (Ig) heavy-chain complementarity determining region 3 (HCDR3)
      residues, whereas affinity maturation contributed predominantly to stabilizing
      the antigen-binding site conformation. Combined, our findings illustrate the
      power of exploring human anti-CSP antibody responses to develop tools for malaria
      control in the mammalian and the mosquito vector and provide a molecular basis
      for the structure-based design of next-generation CSP malaria vaccines.

PMID- 29195814
TI  - Single-arch digital removable complete denture: A workflow that starts from the
      intraoral scan.
AB  - The production of removable dentures from intraoral scans has been problematic.
      In addition, the digital design and fabrication of a single-arch denture cannot
      be routinely managed. The workflow presented provides a proof of concept that an
      optical intraoral scan of the edentulous maxilla is feasible and that a
      functional single-arch maxillary denture can be designed and fabricated using a
      digital protocol.

PMID- 29195815
TI  - Polyetherketoneketone (PEKK), a framework material for complete fixed and
      removable dental prostheses: A clinical report.
AB  - This clinical report demonstrates the use of polyetherketoneketone (PEKK) as a
      framework material with individually luted heat-pressed lithium disilicate glass
      ceramic crowns for an implant-supported complete fixed dental prosthesis (ICFDP)
      and a conventional complete removable dental prosthesis (CRDP). This prosthesis
      design provides a non-computer-aided design and computer-aided manufacturing (CAD
      CAM) option for the fabrication of ICFDPs and CRDPs with individualized ceramic
      crowns for optimal esthetics. The performance of PEKK as a framework material
      needs to be assessed in clinical trials.

PMID- 29195816
TI  - Mechanical properties of resin-ceramic CAD-CAM materials after accelerated aging.
AB  - STATEMENT OF PROBLEM: The development of polymer-based computer-aided design and
      computer-aided manufacturing (CAD-CAM) milling bocks and the limited availability
      of independent studies on these materials make it pertinent to evaluate changes
      in their mechanical properties after simulated aging to identify strengths and
      limitations. PURPOSE: The purpose of this in vitro study was to measure the
      effect of thermocycling on the flexural properties of ceramic, resin, and resin
      ceramic CAD-CAM materials. MATERIAL AND METHODS: Studied materials included Lava
      Ultimate Restorative (LVU; 3M ESPE), Enamic (ENA; VITA Zahnfabrik), Vitablocs
      Mark II (VM2; VITA Zahnfabrik), and Paradigm MZ100 (MZ1; 3M ESPE). Polished
      4*1.2*14 mm bars (n=45 per material) were prepared from standard-size milling
      blocks. The 2 distilled water baths of the thermocycling apparatus were set to 5
      degrees C and 55 degrees C, with a specimen immersion time of 15 seconds and
      transfer time of 4 seconds. Fifteen specimens from each material group were
      subjected to a 3-point flexural test at 3 different thermocycling intervals: 0
      (control), 5000, and 10 000 cycles. The flexural test was performed over a 12-mm
      span with a crosshead speed of 0.5 mm/min. Data were subjected to multiple
      analyses of variance and the Tukey HSD post hoc tests (alpha=.05). RESULTS: Mean
      flexural strength values for 0, 5000, and 10 000 cycles were 133, 130, and 128
      MPa for VM2; 175, 139, and 134 MPa for LVU; 154, 144, and 138 MPa for MZ1; and
      149, 136, and 132 MPa for ENA. Mean flexural modulus values were 51, 52, and 54
      GPa for VM2; 14, 13, and 13 GPa for LVU; 16, 15, and 15 GPa for MZ1; and 31, 30,
      and 31 GPa for ENA. Mean modulus of resilience values were 0.17, 0.16, and 0.15
      MPa for VM2; 10.1, 0.76, and 0.72 MPa for LVU; 0.77, 0.69, and 0.62 MPa for MZ1;
      and 0.42, 0.31, and 0.28 MPa for ENA. A significant difference was found among
      the materials in the mean change of flexural strength (P<.001) and modulus of
      resilience (P<.05) after thermocycling. No significant difference was found among
      the materials in the mean change of flexural modulus after thermocycling
      (P=.113). CONCLUSIONS: The mean flexural strength of resin-ceramics is
      significantly different from that of the feldspathic ceramic control at 0 and
      5000 cycles, but not at 10 000 cycles. The mean modulus of resilience of resin
      ceramics varies significantly after thermocycling, unlike the feldspathic ceramic
      control. Conversely, the mean flexural modulus of tested materials did not vary
      significantly after thermocycling.

PMID- 29195817
TI  - Radial plane tooth position and bone wall dimensions in the anterior maxilla: A
      CBCT classification for immediate implant placement.
AB  - STATEMENT OF PROBLEM: The biological and esthetic challenge of the post
      extraction ridge is relevant to restorative implant dentistry, most significantly
      in the anterior esthetic zone. Previous authors have discussed facial bone wall
      dimensions and classified their variations. A reclassification may be pertinent.
      PURPOSE: The purpose of this observational, clinical study was to introduce a new
      classification system for anterior maxilla tooth position with guidelines for
      immediate implant placement. Data for facial and palatal bone wall height and
      thickness are also presented. MATERIAL AND METHODS: Maxillary anterior teeth
      (n=591) were analyzed as viewed in the radial plane of cone beam computed
      tomography (CBCT) scans from 150 patients. Each tooth was classified according to
      its position and inclination within its alveolus (class I, middle of the
      alveolus; IA, thick facial bone; IB, thin facial bone; class II, retroclined;
      IIA, thick crestal bone; IIB, thin crestal bone; class III, proclined; class IV,
      facially outside bone envelope; class V, both thin facial and palatal bone with
      apical isthmus). Bone thickness was measured for both facial and palatal walls at
      the following points: crestal (A), mid-root (B), apex (C), and 4 mm beyond the
      apex. Bone wall height was also evaluated. RESULTS: A thin facial bone wall
      predominated (<=1 mm) at the crest (83%) and the mid-root point (92%). Most
      palatal walls were thin (<1 mm) at the crest (63%) and thick (>=2 mm) at the mid
      root point (98%) and apex (99%). Class I tooth position accounted for 6.1%, class
      II for 76.5%, class III for 9.5%, class IV for 7.3%, and class V for 0.7%.
      CONCLUSIONS: Maxillary anterior teeth have predominantly thin facial bones,
      making palatal bone thickness a crucial variable. The new classification system
      for radial plane tooth position is a pragmatic clinical analysis for immediate
      implant treatment planning.

PMID- 29195818
TI  - Defining the ascending ramus: A search.
AB  - STATEMENT OF PROBLEM: Lack of an accepted definition for the ascending ramus of
      the mandible means no common reference point is available for clinical or
      research dialogue. PURPOSE: The purpose of this review was to determine whether
      the ascending ramus has been defined, by using a search of published studies.
      MATERIAL AND METHODS: PubMed was searched, using terms "ascending ramus" and
      "mandible." RESULTS: The search found no acceptable definition of the ascending
      ramus of the mandible. CONCLUSIONS: An acceptable definition for the ascending
      ramus of the mandible is lacking, and one is proposed here.

PMID- 29195819
TI  - A modified technique for the intraoral assessment of static occlusal contacts.
AB  - This article describes a procedure in which articulating paper is modified for
      the intraoral assessment of static occlusal contacts. The rectangular-shaped
      articulating paper is modified by creating parallel cuts at 2- to 3-mm intervals
      perpendicular to its long side without completely separating the paper. This
      modification may improve the accuracy in determining occlusal contacts and
      therefore facilitate an occlusal adjustment procedure.

PMID- 29195820
TI  - Modified retention and stability criteria for complete denture wearers: A risk
      assessment tool for impaired masticatory ability and oral health-related quality
      of life.
AB  - STATEMENT OF PROBLEM: Some complete denture wearers report difficulty with daily
      activities, especially activities related to denture retention and stability.
      However, no standard criteria are available for professionally based assessment
      of complete denture quality. PURPOSE: The purpose of this clinical study was to
      determine the association between professionally based assessment of complete
      denture quality, evaluated by conventional and Chulalongkorn University (CU)
      modified Kapur criteria and multiple patient-based outcomes: oral health-related
      quality of life (OHRQoL), eating satisfaction, and masticatory performance. The
      sensitivity and specificity of these criteria in estimating the outcomes were
      investigated. MATERIAL AND METHODS: The participants were 126 individuals with
      removable acrylic resin complete dentures. Denture retention and stability were
      scored based on the Kapur method, with excellent intraobserver reliability
      indicated by a Kappa score of 0.91 to 0.99. The clinical quality of the complete
      denture was classified according to conventional and CU-modified Kapur criteria.
      The participants were interviewed for OHRQoL by using the Thai version of the
      Oral Impacts on Daily Performances (OIDP) index and responses were reported as
      the absence or presence of oral impacts. Participants' satisfaction eating with
      their dentures was determined by using a 5-point Likert scale and dichotomized
      into satisfied and dissatisfied categories. Masticatory performance was evaluated
      by the multiple sieve method of peanut mastication. After adjusting for
      covariates, the associations between denture quality and overall and condition
      specific (CS) impacts on eating and on eating satisfaction were analyzed by using
      binary logistic regression, while its association with masticatory performance
      was determined using linear regression. Goodness-of-fit post estimation was
      conducted to determine the sensitivity and specificity of each denture quality
      criterion in estimating patient-based outcomes. RESULTS: Complete denture
      retention and stability, evaluated by conventional and CU-modified Kapur
      criteria, were associated with multiple patient-based outcomes. However, denture
      stability showed a stronger association than retention. The CU-modified criteria
      assessed the quality of maxillary and mandibular dentures individually and
      revealed a higher sensitivity in estimating all patient-based outcomes.
      CONCLUSIONS: Retention and stability were important indicators in estimating the
      masticatory ability and OHRQoL of complete denture wearers. The CU-modified Kapur
      criteria can identify impaired masticatory ability and OHRQoL in complete denture
      wearers better than conventional criteria.

PMID- 29195821
TI  - Early implant placement for a patient with ectodermal dysplasia: Thirteen years
      of clinical care.
AB  - Patients with ectodermal dysplasia have abnormalities of 2 or more structures
      that originate from the ectoderm. The oral manifestations often include the
      congenital absence of teeth and malformed teeth. This clinical report describes
      the interdisciplinary care from childhood through the definitive dental
      rehabilitation completed at skeletal maturation to replace the missing teeth in a
      patient with ectodermal dysplasia. Treatment began at 9 years of age with an
      implant-assisted mandibular overdenture to improve function and replace the
      missing mandibular teeth. Orthodontic treatment for the consolidation of space,
      composite resin restorations, and interim removable dental prostheses were
      provided to improve esthetics and replace the missing maxillary teeth. Skeletal
      growth was monitored, and orthognathic surgery was performed at the cessation of
      growth. The definitive rehabilitation consisted of a mandibular fixed dental
      prosthesis supported by dental implants and a maxillary removable dental
      prosthesis to restore the patient to esthetics and function.

PMID- 29195822
TI  - Effect of crosslinkers on bond strength stability of fiber posts to root canal
      dentin and in situ proteolytic activity.
AB  - STATEMENT OF PROBLEM: Improved stability of the adhesive interface can be
      obtained using crosslinkers. However, research on the use of crosslinkers in root
      dentin is lacking. PURPOSE: The purpose of this in vitro study was to evaluate
      the effect of crosslinkers on the proteolytic activity of root dentin and on the
      bond strength of resin-cemented fiber posts. MATERIAL AND METHODS: Single root
      canals were obtained from premolars (n=48) and endodontically treated before
      being divided into 4 groups: deionized water (control), 0.5 mol/L carbodiimide,
      5% proanthocyanidin, or 5% glutaraldehyde. After removing the canal sealer, the
      dentin was etched with phosphoric acid, followed by water rinsing and the
      application of the crosslinkers for 60 seconds. Fiber posts were cemented using
      an adhesive (Single Bond 2) and resin cement (RelyX ARC). The roots were then
      transversally sectioned to obtain 1 mm thick specimens from the cervical, middle,
      and apical thirds and then aged for 24 hours or 9 months. Nine roots per group
      were used for the push-out test and 3 for determining the proteolytic activity of
      the root dentin by in situ zymography. Bond strength data were submitted to a
      mixed-model ANOVA and Bonferroni tests (alpha=.05). RESULTS: Only
      proanthocyanidin negatively affected the 24-hour bond strength. After 9 months, a
      significant decrease in bond strength was seen for all groups, except for the
      crosslinked treated specimens from the cervical third of the root canal. Intense
      gelatinolytic activity was detected in the control group after 24 hours but was
      inhibited in the crosslinker-treated groups. Proteolytic activity was also not
      detected after 9 months for the groups treated with the crosslinkers,
      irrespective of the root canal third. Conversely, proteolytic activity increased
      for the specimens from the control group. CONCLUSIONS: Although no proteolytic
      activity was detected in the hybrid layers along the entire root canal, dentin
      biomodification with crosslinkers was effective in preventing bond strength loss
      only in the cervical third.

PMID- 29195823
TI  - Quantitative percussion diagnostics as an indicator of the level of the
      structural pathology of teeth: Retrospective follow-up investigation of high-risk
      sites that remained pathological after restorative treatment.
AB  - STATEMENT OF PROBLEM: Structural damage may remain even after a tooth is
      restored. Conventional diagnostic aids do not quantify the severity of structural
      damage or allow the monitoring of structural changes after restoration. PURPOSE:
      The purpose of this retrospective clinical study was to provide an in-depth
      analysis of 9 high-risk sites after restoration. The analysis followed structural
      defects found upon disassembly, restorative materials used, therapeutic
      procedures provided, current longevity, and long-term quantitative percussion
      diagnostics (QPD) to monitor results. The hypothesis was that QPD can be used to
      quantify positive and negative changes in structural stability. MATERIAL AND
      METHODS: Sixty sites requiring restoration were part of an institutional review
      board-approved clinical study. Each participant was examined comprehensively,
      including QPD testing, at each follow-up. Long-term changes in normal fit error
      (NFE) values after restoration were evaluated according to a pathology rating
      system established in an earlier publication. Nine highly compromised sites were
      chosen for further analysis and monitored for an additional 6 years. RESULTS: Of
      the 9 high-risk sites (NFE>0.04), 7 sites improved and 2 sites deteriorated.
      Potential causes for each trend were documented. CONCLUSIONS: The data support
      the hypothesis that QPD can be used to monitor changes in structural stability
      after restoration. Knowledge of changes in advance of any symptoms allows further
      preventive or therapeutic intervention before serious structural damage can
      occur. Follow-up QPD indications of site improvement can also assure the
      clinician of the desired structural outcome.

PMID- 29195824
TI  - Pseudotumor cerebri syndrome in a patient with narcolepsy type 1.
AB  - Type 1 narcolepsy (NT1) is a chronic primary disorder of hypersomnolence
      characterized by excessive daytime sleepiness, cataplexy, sleep paralysis,
      hypnagogic hallucinations and disrupted nocturnal sleep. NT1 is linked to
      hypothalamic hypocretin deficiency, strongly associated with Human Leukocyte
      Antigen (HLA) marker DQB1*06:02 and of probable autoimmune origin. NT1 is usually
      associated with increased rates of overweight and obesity, and sometimes with
      increases in overnight blood pressure and increased rates of hypoventilation with
      raised CO2 levels overnight. Many of these are predisposing factors for
      pseudotumor cerebri syndrome (PTCS). We present a case of a young girl with both
      NT1 and PTCS that responded well to treatment with acetazolamide after early
      identification, with improvement of headache and resolution of hypoventilation.

PMID- 29195825
TI  - Meta-Analysis of the Safety and Efficacy of the Oral Anticoagulant Agents
      (Apixaban, Rivaroxaban, Dabigatran) in Patients With Acute Coronary Syndrome.
AB  - The significance of adding new oral anticoagulants (NOACs) to antiplatelet
      therapy in patients with acute coronary syndrome (ACS) is unclear. We conducted a
      meta-analysis to assess the safety and efficacy of adding NOACs (apixaban,
      rivaroxaban, and dabigatran) to single antiplatelet agent (SAP) or dual
      antiplatelet therapy (DAPT) in patients with ACS. Seven randomized controlled
      trials were selected using PubMed or MEDLINE, Scopus, and Cochrane library
      (inception to August 2017). The summary measure was random effects hazard ratio
      (HR) with 95% confidence interval (CI). The primary safety outcome was clinically
      significant bleeding. The secondary efficacy outcome was major adverse
      cardiovascular events (MACE; composite of myocardial infarction, stroke, and all
      cause mortality). In 31,574 patients, addition of NOAC to SAP did not increase
      the risk of clinically significant bleeding (HR 0.82, 95% CI 0.56 to 1.20, p =
      0.31); however, the risk of clinically significant bleeding was significantly
      increased with NOAC plus DAPT (HR 2.24, 95% CI 1.75 to 2.87, p < 0.001). NOACs
      had no statistically beneficial effect on MACE when used with SAP (HR 0.82, 95%
      CI 0.66 to 1.04, p = 0.10); however, a modest reduction in MACE was observed when
      NOACs were combined with DAPT (HR 0.86, 95% CI 0.78 to 0.93, p < 0.001). In
      conclusion, in patients with ACS, the addition of NOAC to DAPT resulted in
      increased risk of clinically significant bleeding, whereas only a modest
      reduction in MACE was achieved. The addition of NOACs to SAP did not result in
      significant reduction of MACE or increase in clinically significant bleeding.

PMID- 29195826
TI  - Some Cardiologists' Perspective on Past, Current, and Future of Sleep Medicine.
AB  - An accumulating body of evidence has highlighted the importance of sleep in
      cardiovascular health. Sleep apnea (SA) is a highly common condition in patients
      with cardiovascular comorbidities. Although awareness about the importance of
      diagnosis and treatment of SA among cardiologists has increased, incorporating it
      into daily practice has been challenging. We briefly review the current state of
      sleep medicine in the United States and provide views on how the cardiology
      community can more actively participate in SA care to deliver higher quality of
      care. We propose a cardiology-led patient-centered SA collaborative care model to
      effectively achieve this.

PMID- 29195827
TI  - Usefulness of a Rounding Cardiologist in a Skilled Nursing Facility to Reduce
      Hospital Readmissions and Costs.

PMID- 29195828
TI  - Blood Pressure Control in Patients Presenting With Type B Aortic Dissection.

PMID- 29195829
TI  - Importance of vancomycin loading doses in intermittent infusion regimens.
AB  - PURPOSE: Delayed achievement of target vancomycin serum concentrations may
      adversely affect clinical outcomes. The objective of this retrospective study was
      to explore the real frequency of loading dose use and to evaluate the impact of
      loading dose for the achievement of vancomycin PK/PD target in adult patients
      treated with intermittent vancomycin. As a secondary aim we determined optimal
      vancomycin loading dose based on individual pharmacokinetic calculations.
      METHODS: Vancomycin pharmacokinetic models were computed using two-compartmental
      analysis. Based on these models AUC24 were calculated. Unpaired t-test was used
      to compare AUC24 achieved in patients treated with and without vancomycin loading
      dose. RESULTS: Vancomycin loading dose was administered only in 17.8% patients.
      Volume of distribution and clearance median values (interquartile range) for
      vancomycin in whole study population (n = 45) were 0.69 (0.55-0.87) L/kg and
      0.0304 (0.0217-0.0501) L/h/kg, respectively. The AUC24 was significantly higher
      in patients taking loading dose compared with the group without loading dose:
      mean (SD) AUC24 was 496 (101) vs. 341 (77) mg h/L. Proportion of patients
      reaching PK/PD goal was 87.5% and 24.3% with and without loading dose
      administration, respectively. Considering individual pharmacokinetic parameters
      optimal vancomycin loading dose was 27.5 mg/kg of body weight. CONCLUSIONS:
      Loading dose administration plays crucial part in rapid attainment of vancomycin
      PK/PD target in adult patient treated with intermittent vancomycin, although it
      is not frequently used in clinical practise. The optimal loading dose of 25-30
      mg/kg of body weight should be routinely administered to adult patients treated
      with intermittent vancomycin.

PMID- 29195830
TI  - Retrograde intrarenal surgery using ureteral access sheaths is a safe and
      effective treatment for renal stones in children weighing <20 kg.
AB  - INTRODUCTION: Surgical treatment of pediatric kidney stones has changed
      dramatically in recent years because of the miniaturization of surgical
      instruments and the availability of intracorporeal lithotripters. The retrograde
      intrarenal surgery (RIRS) technique is nowadays considered an effective and safe
      procedure but studies in very young children are lacking and use of a ureteral
      access sheath (UAS) has also been debated. OBJECTIVE: To assess safety and
      efficacy of RIRS using UAS in children weighing < 20 kg. MATERIALS AND METHODS:
      Data from 13 children weighing <20 kg who underwent RIRS for renal stones were
      collected. A Double-J stent was positioned 14 days before surgery. Demographics,
      stone location, stone number and composition, stone-free status (SFS) and
      complications were evaluated. Descriptive statistics were applied to describe the
      cohort. RESULTS: Thirteen patients, age 3.91 +/- 1.8 years (mean +/- SD),
      underwent 16 RIRS. Mean patient weight and stone burden were 14.88 +/- 3.81 kg
      (range 10-20 kg) and 15.5 +/- 3.8 mm (median 16 mm), respectively. A UAS was used
      in 15 out of 16 (93.8%) procedures. SFS was achieved in 81.3% of cases after the
      first procedure and 100% after auxiliary procedures. Postoperative urinary tract
      infections with fever (Clavien II) were observed in two (12.5%) patients.
      Hydrocalyx (Clavien IIIb) was noted in one (6.3%) patient. Patients with stones
      located in the lower polar calices (p = 0.024) and with mixed composition (p =
      0.036) had a greater prevalence of complications than those with calculi of other
      compositions located in other sites. After a mean follow-up of 22.4 months no
      cases of ureteral strictures or vesicoureteral reflux were observed (Table).
      DISCUSSION: The current findings support previous evidence showing safety and
      efficacy of RIRS with use of the UAS in pre-stented very young children. In our
      experience RIRS seems to be an effective and safe option with a stone-free rate
      of 81.3% and only 1 severe complication (Clavien-Dindo grade IIIb) and no long
      term complications. This study is, to date, the first to examine the safety and
      efficacy of RIRS using UAS for the treatment of intrarenal stones in a selected
      cohort of pre-school patients weighing <20 kg. CONCLUSIONS: RIRS using UAS is an
      effective and safe procedure for treating kidney stones in pre-school patients
      weighing <20 kg without complications at both short and long term follow up.
      Stones of mixed composition located in the lower polar calices are associated
      with a greater risk of postoperative complications.

PMID- 29195831
TI  - Bladder exstrophy closure in the newborn period with external pelvic fixation
      performed without osteotomy: A preliminary report.
AB  - BACKGROUND: Successful primary bladder closure is the most crucial element for
      urinary continence in patients with classic bladder exstrophy (CBE). In the
      newborn period, bladder closure can be performed in the first 48 h without pelvic
      osteotomy or external fixation, but requires postoperative lower extremity
      immobilization (i.e., spica cast, Bryant's or Buck's traction). OBJECTIVE: To
      present a novel surgical approach for primary bladder closure for CBE using two
      pin external fixation without pelvic osteotomy, and without postoperative lower
      extremity immobilization. STUDY DESIGN: A retrospective chart review of patients
      with CBE was performed at the current institution from 2000 to 2016, including
      all primary bladder closures with external fixation and without osteotomy or
      lower extremity immobilization. Patients were discharged with the external
      fixator in place, which was later removed in clinic. Baseline clinical and
      demographic variables, and follow-up data were recorded. RESULTS: Thirteen
      patients were analyzed; eight (61.5%) were male. Pre-operative intersymphysial
      distance was 3.68 +/- 1.0 cm (2.0-5.0). Mean follow-up was 56.8 +/- 40.3 months
      (10-131). One patient had a partial bladder neck dehiscence, due to pin
      displacement on postoperative day 1: he had the lowest gestational age of 34
      weeks (Summary table). DISCUSSION: This approach used external fixation to bring
      the pubic bones together intra-operatively, and to decrease the tension in
      closing the pelvic ring and abdominal wall without osteotomy. External fixation
      with osteotomy and long-term immobilization, or using a spica cast without
      osteotomy offered the added advantage of improved wound care, due to lack of
      lower limb immobilization, less patient discomfort, and facilitation of
      mother/caregiver and newborn bonding. CONCLUSION: The two-pin external fixator
      without osteotomy as an adjunct to primary bladder closure in CBE patients was
      technically feasible. At the current institution this approach had an equivalent
      success rate to previous reports in the literature for primary bladder closure,
      decreased the length of hospital stay, and precluded the need for lower extremity
      immobilization. Early data for bladder capacity were encouraging.

PMID- 29195832
TI  - Variation in the use of laparoscopy with inguinal hernia repairs in a sample of
      pediatric patients at children's hospitals.
AB  - INTRODUCTION/BACKGROUND: Metachronous contralateral inguinal hernias (MCH) occur
      in approximately 10% of pediatric patients following unilateral inguinal hernia
      repairs (UIHR). Laparoscopic evaluation of the contralateral internal ring is a
      method of identifying high-risk individuals for prophylactic contralateral
      exploration and repair. OBJECTIVE: The objective of this study was to assess
      variation in utilization of diagnostic laparoscopy, and report costs associated
      with the evaluation of a contralateral patent processus vaginalis during hernia
      repair in pediatric hospitals. STUDY DESIGN: The Pediatric Health Information
      System database was searched to identify outpatient surgical encounters for
      pediatric patients with a diagnosis of inguinal hernia during a 1-year period
      (2014). Records were identified that contained diagnostic codes for unilateral or
      bilateral inguinal hernia in combination with a procedure code for open hernia
      repair with or without diagnostic laparoscopy. RESULTS: After exclusions there
      were 3952 hernia repairs performed at 30 hospitals; median age was 4 years (IQR 1
      7), 78.8% were male, and 64.9% Caucasian. Three-quarters (76.7%) had UIHR, 8.6%
      had unilateral repairs with laparoscopy (UIHRL), 12.2% had bilateral inguinal
      hernia repairs (BIHR), and 2.4% had bilateral repairs with laparoscopy (BIHRL).
      Where laparoscopy was used, 78% resulted in a unilateral repair and 22% in a
      bilateral procedure. The percent of patients undergoing laparoscopy varied from 0
      to 57% among hospitals, and 0-100% among surgeons. Pediatric surgeons were more
      than three times more likely to perform a diagnostic laparoscopy compared with
      pediatric urologists. Median adjusted costs were $2298 (IQR 1659-2955) for UIHR,
      $2713 (IQR 1873-3409) for UIHRL, $2752 (IQR 2230-3411) for BIHR, and $2783 (IQR
      2233-3453) for BIHRL. Median costs varied over two-fold among hospitals ($1310
      4434), and over four-fold among surgeons ($948-5040). DISCUSSION: Data suggested
      that <10% of patients with clinically unilateral inguinal hernias developed MCH.
      A negative diagnostic laparoscopy ensured that 0.9-1.31% developed MCH. However,
      up to 30% of patients underwent contralateral exploration/repair when diagnostic
      laparoscopy was used. The current study found increased costs associated with the
      use of laparoscopy, with considerable variation in costs among surgeons and
      hospitals. These data elucidate competing financial and clinical consequences
      associated with the use of diagnostic laparoscopy with clinically unilateral
      hernias. CONCLUSIONS: Variation existed in the use of laparoscopy during inguinal
      hernia repairs and associated costs within the current sample from children's
      hospitals in the United States. The additional costs of laparoscopic evaluation
      must be considered against the clinical utility and therapeutic consequences of
      identifying individuals with a higher risk of metachronous contralateral inguinal
      hernia.

PMID- 29195833
TI  - Lutein levels in arterial cord blood correlate with neuroprotein activin A in
      healthy preterm and term newborns: A trophic role for lutein?
AB  - BACKGROUND: Lutein (LT) is a naturally occurring xanthophyll carotenoid most
      predominant in the central nervous system (CNS), but its neurotrophic role is
      still debated. We therefore investigated whether cord blood concentrations
      correlated with a well-established neurobiomarker, namely activin A. METHODS: We
      conducted a prospective study on the distribution of LT and activin A in arterial
      cord blood of healthy preterm (n=50) and term (n=82) newborns according to weeks
      of gestational age (wGA) and gender. RESULTS: LT and activin A showed a pattern
      of concentration characterized by higher levels (P<0.01, for all) at 33-36 wGA
      followed by a progressive decrease (P<0.01, for all) from 37 onwards with a dip
      at term. Both LT and activin A were gender-dependent with significantly (P<0.01,
      for all) higher levels in all recruited females and after sub-grouping for
      preterm and term births. LT (R=0.33; P<0.001) correlated with wGA at sampling.
      There were significant positive correlations between lutein and activin A in male
      (R=0.93; P<0.001) and female (R=0.89; P<0.001) groups. CONCLUSIONS: The present
      data showing a correlation between LT and activin A support the notion of a
      neurotrophic role gender-dependent for LT and open the way to further
      investigations correlating LT with well-established biochemical markers of CNS
      development/damage.

PMID- 29195834
TI  - Diacerein alleviates kidney injury through attenuating inflammation and oxidative
      stress in obese insulin-resistant rats.
AB  - A link between inflammation with obesity and metabolic syndrome has been found in
      patients with chronic kidney disease (CKD). Diacerein is an anthraquinone used to
      treat osteoarthritis that exerts anti-inflammatory action by inhibiting the
      synthesis and activity of proinflammatory cytokines. This study aimed to
      investigate the protective effect of diacerein on renal function and renal
      organic anion transporter 3 (Oat3) function in obese insulin-resistant condition.
      Obese insulin-resistant rats were induced by feeding a high-fat diet in male
      Wistar rats for 16 weeks. Diacerein or metformin (positive control) (30mg/kg/day)
      was administered orally for 4 weeks after insulin resistance had been confirmed.
      Obese insulin-resistant rats showed an impaired renal function as indicated by
      the increased serum creatinine and microalbuminuria along with the decreased
      renal Oat3 function and expression. Importantly, diacerein treatment not only
      improved insulin resistance but also restored renal function. The decreased renal
      malondialdehyde level, expressions of PKCalpha, angiotensin 1 receptor (AT1R),
      Nrf2, and HO-1, and increased expression of SOD2 were observed in diacerein
      treatment group, indicating the attenuation of renal oxidative stress condition.
      Moreover, renal inflammation and renal damage were also alleviated in diacerein
      treated rats. Our results demonstrated for the first time that diacerein was
      effective to improve renal function and renal Oat3 function in obese insulin
      resistance condition mediated by suppressing renal oxidative stress and
      inflammation. These findings suggest that anti-inflammatory agents can be used
      therapeutically to improve metabolic disorder and prevent organ dysfunctions in
      pre-diabetic condition.

PMID- 29195835
TI  - Absence of the biliverdin reductase-a gene is associated with increased
      endogenous oxidative stress.
AB  - Bilirubin, a byproduct of heme catabolism, has been shown to be an effective
      lipid-soluble antioxidant in vitro. Bilirubin is able to inhibit free radical
      chain reactions and protects against oxidant-induced damage in vitro and ex vivo.
      However, direct evidence for bilirubin's antioxidant effects in vivo remains
      limited. As bilirubin is formed from biliverdin by biliverdin reductase, we
      generated global biliverdin reductase-a gene knockout (Bvra-/-) mice to assess
      the contribution of bilirubin as an endogenous antioxidant. Bvra-/- mice appear
      normal and are born at the expected Mendelian ratio from Bvra+/- x Bvra+/-
      matings. Compared with corresponding littermate Bvra+/+ and Bvra+/- animals, Bvra
      /- mice have green gall bladders and their plasma concentrations of biliverdin
      and bilirubin are approximately 25-fold higher and 100-fold lower, respectively.
      Naive Bvra-/- and Bvra+/+ mice have comparable plasma lipid profiles and low
      molecular weight antioxidants, i.e., ascorbic acid, alpha-tocopherol and
      ubiquinol-9. Compared with wild-type littermates, however, plasma from Bvra-/-
      mice contains higher concentrations of cholesteryl ester hydroperoxides (CE-OOH),
      and their peroxiredoxin 2 (Prx2) in erythrocytes is more oxidized as assessed by
      the extent of Prx2 dimerization. These data show that Bvra-/- mice experience
      higher oxidative stress in blood, implying that plasma bilirubin attenuates
      endogenous oxidative stress.

PMID- 29195836
TI  - Is the risk of antipsychotic polypharmacy discontinuation dependent on the agents
      used?
AB  - This study assesses the risks and benefits of switching from two to one
      antipsychotic among participants on two non-clozapine oral antipsychotics, and
      among those on combinations involving either clozapine or an injectable
      antipsychotic. Ninety adult participants with schizophrenia or schizoaffective
      disorder were assigned to stay on polypharmacy or to switch to monotherapy. Half
      of these participants were receiving combinations of non-clozapine oral
      antipsychotics and half were receiving combinations involving either clozapine or
      an injectable antipsychotic. Participants were assessed every 60 days for one
      year. We examined differences in symptom and side effect trajectories as a
      function of group assignment and time for both medication groups. Participants
      who switched from two to one non-clozapine oral antipsychotic experienced
      significant increases in symptoms relative to stay participants. They also saw
      significant side effect benefits. Switch participants on combinations involving
      clozapine or an injectable antipsychotic did not differ over time from stay
      participants on either symptom or side effect measures. It appears that patients
      on these combinations can be safely switched to monotherapy. While there may be
      symptom related risks associated with switching patients on combinations of non
      clozapine oral antipsychotics, there are significant health related benefits.
      Clozapine or injectable antipsychotic monotherapy are recommended options.

PMID- 29195837
TI  - Evaluation of the efficacy of tongue-lip adhesion in Pierre Robin sequence.
AB  - OBJECTIVE: Tongue-lip adhesion may be used to relieve obstructive sleep apnoea in
      infants with Pierre Robin sequence (PRS), but only a few studies have objectively
      evaluated its efficacy. The purpose of this study was to evaluate the results of
      tongue-lip adhesion by polysomnography. MATERIEL AND METHODS: A single-centre
      retrospective study was conducted in infants with PRS treated by tongue-lip
      adhesion from 2004 to 2015, in whom at least laryngotracheal endoscopy and
      polysomnography were performed. The variables collected were the syndromic
      diagnosis, demographic data, respiratory management before tongue-lip adhesion,
      symptoms, and additional airway interventions. Obstructive sleep apnoea was
      classified into 3 groups according to severity. Polysomnography was performed one
      month after tongue-lip adhesion. Statistical analysis was performed with Wilcoxon
      signed-rank test with a limit of statistical significance of P<0.005. RESULTS:
      Thirty-seven subjects in whom tongue-lip adhesion was performed at a mean age of
      45 days (8 to 210 days) were included. Thirty-one patients had isolated PRS and 6
      patients had associated anomalies. All patients had confirmed severe obstructive
      sleep apnoea. All patients required respiratory support prior to surgery: 8
      intubated patients, 15 patients with noninvasive ventilation and 14 patients with
      nasopharyngeal airways. Eight patients had bradycardia before tongue-lip
      adhesion. All parameters were improved on postoperative polysomnography: oxygen
      saturation, hypercapnia, apnoea-hypopnoea index, bradycardia (P<0.005). Only 8
      patients had persistent severe obstructive sleep apnoea and required tracheostomy
      (n=5) or noninvasive ventilation (n=3). No significant correlation was observed
      between treatment success and any predictive variables. CONCLUSION: Tongue-lip
      adhesion improved airway obstruction in all infants with PRS and resolved
      obstructive sleep apnoea in 29 patients. However, 8 patients required additional
      airway interventions.

PMID- 29195838
TI  - A phenomenological analysis of eco-evolutionary coupling under dilution.
AB  - Evolutionary dynamics experienced by mixed microbial populations of cooperators
      and cheaters has been examined in experiments in the literature using a protocol
      of periodic dilution to investigate the properties of resilience and adaptability
      to environmental changes. Data depicted on an appropriate phase diagram indicate,
      among other features, a stable equilibrium point at which cooperators and
      cheaters coexist (Sanchez and Gore, 2013). We present here a phenomenological
      analysis of these data focusing on an eco-evolutionary-game perspective. To that
      end, we work on an extension of the model proposed in Tao and Cressman (2007).
      It's original version takes into account changes of the total population density
      while the individuals experience a pairwise Prisoners Dilemma game. The extension
      devised here contains a dilution parameter to conform with the experimental
      procedure, in addition to a term accounting for Allee effects. In contrast to
      other descriptions proposed in similar contexts, however, the model here does not
      account for assortative encounters, group or kin selection. Nonetheless, it
      describes surprisingly well both qualitatively and quantitatively the features of
      the observed phase diagram. We discuss these results in terms of the behavior of
      an effective payoff matrix defined accordingly.

PMID- 29195839
TI  - The ventromedial hypothalamic nucleus plays an important role in anxiolytic-like
      effect of neuropeptide S.
AB  - Neuropeptide S (NPS), the endogenous neuropeptide ligand of NPSR, has been
      reported to regulate anxiety-related behavior involved in multiple brain regions,
      including amygdale, locus coeruleus and Barrington's nucleus. However, little
      research has been conducted on the anxiolytic-like behaviors of NPS on the
      hypothalamus, which was an important area in defensive behavior. Here, we
      investigated a role of hypothalamus in anxiolytic-like behaviors of NPS. We found
      that NPSR protein of mouse distributed mainly in the ventromedial hypothalamus
      (VMH). And in the single prolonged stress model (SPS), the results showed that
      NPS mRNA of the mice exposed to SPS was significantly higher than control, while
      NPSR mRNA was remarkable lower than control in hypothalamus. Further studies
      found that NPS intra-VMH infusion dose-dependently (1, 10 and 100pmol) induced
      anxiolytic effects, using elevated plus maze and open field tests. These
      anxiolytic effects could be blocked by NPSR antagonist (SHA68), but not by
      picrotoxin (a GABAA receptor antagonist) and sacolfen (a GABAB receptor
      antagonist). Meanwhile, our data showed that the expression of c-Fos was
      significantly increased in VMH after NPS delivered into the lateral ventricles.
      These results cast a new light on the hypothalamic nucleus in the anxiolytic-like
      effect of NPS system.

PMID- 29195842
TI  - Stent in false versus true lumen of left anterior descending artery identified on
      cardiac computed tomography.

PMID- 29195841
TI  - Incidental pulmonary nodules in emergent coronary CT angiography for suspected
      acute coronary syndrome: Impact of revised 2017 Fleischner Society Guidelines.
AB  - BACKGROUND: Pulmonary nodules (PN) are frequently detected incidentally during
      coronary computed tomography angiography (CTA). We evaluated whether the 2017
      Fleischner Society guidelines may result in a decrease of follow-up testing of
      incidental PN as compared to prior guidelines in patients undergoing coronary
      CTA. METHODS: We conducted a retrospective study of a registry of emergency
      department patients who underwent coronary CTA for acute coronary syndrome
      assessment between 2012 and 2017. Based on guidelines, patients <35 years,
      history of cancer, or prior exams showing stability of PN were excluded. Patients
      >60 years, history of smoking, irregular/spiculated PN morphology, or PN size >20
      mm were classified as high-risk for lung cancer. Radiological findings pertaining
      to PN were identified (PN size, morphology, quantity) through review of radiology
      reports. PN follow-up recommendations were established using 2017 Fleischner
      Society Guidelines and compared with prior guidelines for solid (2005) and
      subsolid (2013) PN. Data were analyzed with Student's t-test. RESULTS: The
      registry included 2066 patients (female 45.1%, 52.9 +/- 11.0 years), of which 578
      (28.0%) reported PN. 438 of those (21.2%) were eligible for guideline-based
      follow-up evaluation. 205 (4 6.8%) were classified as high-risk for lung cancer.
      2017 guidelines reduced the number of individuals requiring follow-up by 64.5%,
      from 264 (12.8%) to 94 patients (4.5%) when compared to prior guidelines (p <
      0.001). The minimum number of follow-up chest CTs decreased by 55.8% from 430 to
      190 (p < 0.001). CONCLUSION: Application of the 2017 Fleischner Society
      Guidelines resulted in a significant decrease of follow-up testing for incidental
      PN in patients undergoing coronary CTA for suspected acute coronary syndrome.

PMID- 29195840
TI  - Membrane estrogen receptor signaling impacts the reward circuitry of the female
      brain to influence motivated behaviors.
AB  - Within the adult female, estrogen signaling is well-described as an integral
      component of the physiologically significant hypothalamic-pituitary-gonadal axis.
      In rodents, the timing of ovulation is intrinsically entwined with the display of
      sexual receptivity. For decades, the importance of estradiol activating
      intracellular estrogen receptors within the hypothalamus and midbrain/spinal cord
      lordosis circuits has been appreciated. These signaling pathways primarily
      account for the ability of the female to reproduce. Yet, often overlooked is that
      the desire to reproduce is also tightly regulated by estrogen receptor signaling.
      This lack of emphasis can be attributed to an absence of nuclear estrogen
      receptors in brain regions associated with reward, such as the nucleus accumbens,
      which are associated with motivated behaviors. This review outlines how membrane
      localized estrogen receptors affect metabotropic glutamate receptor signaling
      within the rodent nucleus accumbens. In addition, we discuss how, as estrogens
      drive increased motivation for reproduction, they also produce the untoward side
      effect of heightening female vulnerability to drug addiction.

PMID- 29195843
TI  - Influence of irregular heart rhythm on radiation exposure, image quality and
      diagnostic impact of cardiac computed tomography angiography in 4,339 patients.
      Data from the German Cardiac Computed Tomography Registry.
AB  - BACKGROUND: Coronary computed tomography angiography (coronary CTA) provides non
      invasive evaluation of the coronary arteries with high precision for the
      detection of significant coronary artery disease (CAD). AIM: To investigate
      whether irregular heart rhythm including atrial fibrillation and premature beats
      during data acquisition influences (i) radiation and contrast media exposure,
      (ii) number of non-evaluable coronary segments and (iii) diagnostic impact of
      coronary CTA. METHODS: Twelve tertiary care centers with >=64 slice CT scanners
      and >=5 years of experience with cardiovascular imaging participated in this
      registry. Between 2009 and 2014, 4339 examinations were analysed in patients who
      underwent clinically indicated coronary CTA for suspected CAD. Clinical and
      epidemiologic data were gathered from all patients. In addition, clinical
      presentation, heart rate and rhythm during the scan, Agatston score, radiation
      and contrast media exposure and the diagnostic impact of coronary CTA were
      systematically analysed. RESULTS: Of 4339 patients in total, 260 (6.0%) had
      irregular heart rhythm, whereas the remaining 4079 (94.0%) had stable sinus
      rhythm. Patients with irregular heart rhythm were older (63.2 +/- 12.5yrs versus
      58.6 +/- 11.4yrs. p < 0.001), exhibited a higher rate of pathologic stress tests
      before CTA (37.1% versus 26.1%, p < 0.01) and higher heart rates during CTA
      compared to those with sinus rhythm (62.5 +/- 11.6bpm versus 58.9 +/- 8.5bpm, p <
      0.001). Both contrast media exposure and radiation exposure were significantly
      higher in patients with irregular heart rhythm (90 mL (95%CI = 80-110 mL) versus
      80 mL (95%CI = 70-90 mL) and 6.2 mSv (95%CI = 2.5-11.7) versus 3.3 mSv (95%CI =
      1.7-6.9), p < 0.001 for both). Coronary CTA excluded significant CAD less
      frequently in patients with irregular heart rhythm (32.9% versus 44.8%, p <
      0.001). This was attributed to the higher rate of examinations with at least one
      non-diagnostic coronary segment in patients with irregular heart rhythm (10.8%
      versus 4.6%, p < 0.001). Subsequent invasive angiography could be avoided in
      47.2% of patients with irregular heart rhythm compared to 52.9% of patients with
      sinus rhythm (p = NS), whereas downstream stress testing was recommended in 3.2%
      of patients with irregular heart rhythm versus 4.0% of patients with sinus rhythm
      (p = NS). CONCLUSION: A significant number of patients scheduled for coronary CTA
      have irregular heart rhythm in a real-world clinical setting. In such patients,
      heart rate during coronary CTA is higher, possibly resulting in (i) higher
      radiation and contrast agent exposure and (ii) more frequent coronary CTA
      examinations with at least one non-diagnostic coronary artery segment. However,
      this does not seem to lead to increased downstream stress testing or subsequent
      invasive procedures.

PMID- 29195844
TI  - Leaflet thrombosis following transcatheter aortic valve implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly being
      offered to high-risk patients with symptomatic aortic valve stenosis. Recent
      reports have suggested a high incidence of subclinical leaflet thrombosis
      following bioprosthestic aortic valve replacement. We report the frequency and
      clinical presentation of leaflet thrombosis identified by cardiac CT in patients
      referred for follow-up contrast enhanced CT angiography following TAVI. METHODS:
      91 consecutive patients referred for follow-up contrast-enhanced CT angiography
      following TAVI were screened for inclusion in this analysis. Out of these, 13
      patients were excluded. All CT examinations were performed using a 2nd or a 3rd
      generation dual-source system (Somatom Definition Flash/Force, Forchheim,
      Germany). In all patients, retrospectively ECG-gated spiral acquisition with tube
      modulation was performed to allow for assessment of leaflet motion. All
      prostheses were analyzed for presence of leaflet thrombosis defined as hypo
      attenuated leaflet thickening with or without leaflet restriction. Post
      procedural antithrombotic regimen as well as symptom status was documented in all
      patients. RESULTS: 78 consecutive patients (35 males, 81 +/- 4 years) were
      analyzed. TAVI had been performed in all patients (76 transfemoral access, 2
      transapical access) with either balloon-expandable prostheses (4 Sapien XT, 64
      Sapien 3) or self-expandable prostheses (5 SJM Portico, 5 Symetis Acurate).
      Follow-up CT angiography was performed at a median of 4 months following index
      procedure (Interquartile range 1 month). Leaflet thrombosis was detected in 18
      patients (23%, 14 Sapien 3, 1 Sapien XT, 2 SJM Portico, 1 Symetis Acurate). In
      patients with leaflet thickening on CT, only 11% were on either oral
      anticoagulation or new oral anticoagulants versus 50% for patients with no
      leaflet thickening (p 0.002). In patients with leaflet thrombosis, 3 leaflets
      were affected in 5 patients, 2 leaflets in 5 patients and in 8 patient only 1
      leaflet was affected. Clinical symptoms (angina, dyspnea or both) were reported
      in 2/18 patients with leaflet thrombosis (11%) and in both patients a significant
      increase of the mean echocardiographic gradient over the prosthesis was
      documented. The peak and mean echocardiographic gradients obtained at the day of
      CT examination was significantly higher in symptomatic patients versus
      asymptomatic patients (peak 46 +/- 7 vs. 23 +/- 11 mmHg, mean 29 +/- 7 vs. 12 +/-
      6 mmHg, p = 0.01 and 0.002, respectively). Follow-up CT was available for 4
      patients with complete resolution of the hypo-attenuated leaflet thickening
      following treatment. CONCLUSION: Leaflet thrombosis following TAVI is a
      relatively frequent finding in patients referred for contrast enhanced CT
      angiography following TAVI. In the majority of patients it follows a subclinical
      course and is substantially more frequent in individuals who are not on oral
      anticoagulation. However, in patients with relevant increase in prosthetic
      gradients, symptomatic presentations are possible.

PMID- 29195845
TI  - December 2017.

PMID- 29195846
TI  - Association of fibulin-3 concentrations with the presence and severity of knee
      osteoarthritis: A cross-sectional study.
AB  - BACKGROUND: Fibulin-3, a member of the extracellular matrix glycoproteins family,
      negatively regulates chondrocyte differentiation. This study aims to assess the
      correlation of fibulin-3 concentrations with the presence and severity of knee
      osteoarthritis. METHODS: This cross-sectional study was performed in a population
      of 209 knee osteoarthritis subjects who received hyaluronic acid treatment and
      165 healthy controls. Knee osteoarthritis diagnosis was made according to the
      criteria of the American College of Rheumatology. Osteoarthritis severity was
      scored by the Kellgren-Lawrence grading method. Synovial fluid was obtained from
      the knees of osteoarthritis subjects who received the treatment of hyaluronic
      acid injection for the first time. Serum and synovial fluid fibulin-3
      concentrations were examined by enzyme-linked immunosorbent assay method.
      RESULTS: Mann-Whitney U-test showed that there were higher serum fibulin-3
      concentrations in the case group compared with the controls. Higher serum and
      synovial fluid fibulin-3 concentrations were found in knee osteoarthritis
      subjects compared with those with Kellgren-Lawrence grades 2 and 3. Knee
      osteoarthritis subjects with Kellgren-Lawrence grade 3 had higher serum and
      synovial fluid fibulin-3 concentrations compared with those with Kellgren
      Lawrence grade 2. Serum and synovial fluid fibulin-3 concentrations were
      significantly correlated with Kellgren-Lawrence grading after Pearson correlation
      analysis (r=0.532, P<0.001 and r=0.613, P<0.001). Multinomial logistic regression
      analysis demonstrated a significant association between serum and synovial fluid
      fibulin-3 concentrations with Kellgren-Lawrence grades (P<0.001 and P<0.001).
      CONCLUSION: Serum and synovial fluid fibulin-3 concentrations were correlated
      with the presence and severity of knee osteoarthritis.

PMID- 29195847
TI  - Trochanteric Bursitis Following Primary Total Hip Arthroplasty: Incidence,
      Predictors, and Treatment.
AB  - BACKGROUND: Trochanteric bursitis (TB) remains a common complication after total
      hip arthroplasty (THA), with an incidence between 3% and 17%, depending on the
      surgical approach, with the posterior approach (PA) being relatively protective
      compared to the lateral approach. The purposes of this study were to determine
      the incidence of TB after primary THA, identify potential risk factors for TB,
      and examine the utility of different modes of treatment. METHODS: Retrospective
      cohort data of 990 primary THAs performed in a single institution, including 613
      PAs and 377 direct anterior approaches (DAAs), were analyzed. Data abstracted
      included demographic data, operative diagnosis, comorbidities, radiographic
      assessment, and other specific predictors of interest that were compared between
      patients diagnosed with TB following THA and controls. RESULTS: The incidence of
      TB following primary THA was 5.4% (54/990) for the entire cohort. The incidence
      did not differ significantly between the PA and DAA (5% vs 6.1%, respectively; P
      = .47). Charlson comorbidity index and American Society of Anesthesiology did not
      differ significantly in the TB group. Lumbar spinal stenosis and history of past
      smoking were significantly more common in patients who developed TB (P = .03, P =
      .01, respectively), but did not continue to be significant risk factors on
      multivariate analysis. All patients were treated nonoperatively by the time of
      final follow-up. Seventy-four percent required a local steroid injection and 30%
      required treatment with more than one modality. CONCLUSION: The occurrence of TB
      is not influenced by the surgical approach (PA or DAA), and could not be
      predicted by specific comorbidities or radiographic measurements. However, it can
      be effectively treated conservatively in most cases.

PMID- 29195848
TI  - Does Surgical Approach Affect Outcomes in Total Hip Arthroplasty Through 90 Days
      of Follow-Up? A Systematic Review With Meta-Analysis.
AB  - BACKGROUND: The choice between anterior approach (AA) and posterior approach (PA)
      in primary total hip arthroplasty (THA) is controversial. Previous reviews have
      predominantly relied on data from retrospective studies. METHODS: This systematic
      review included prospective studies comparing postoperative outcomes through 90
      days of AA vs PA in primary THA. Outcomes were pain severity, narcotic usage, hip
      function using Harris Hip Score, and complications. Random effects meta-analysis
      was performed for all outcomes. Efficacy data were reported as standardized mean
      difference (SMD) where values of 0.2, 0.5, 0.8, and 1.0 were defined as small,
      medium, large, and very large effect sizes, respectively. Complications were
      reported as the absolute risk difference (RD) where a positive value implied
      higher risk with AA and a lower value implied lower risk with AA. RESULTS: A
      total of 13 prospective comparative studies (7 randomized) with patients treated
      with AA (n = 524) or PA (n = 520) were included. The AA was associated with lower
      pain severity (SMD = -0.37, P < .001), lower narcotic usage (SMD = -0.36, P =
      .002), and improved hip function (SMD = 0.31, P = .002) compared to PA. No
      differences between surgical approaches were observed for dislocation (RD = 0.2%,
      P = .87), fracture (RD = 0.2%, P = .87), hematoma (RD = 0%, P = .99), infection
      (RD = 0.2%, P = .85), thromboembolic event (RD = -0.9%, P = .42), or reoperation
      (RD = 1.3%, P = .26). Conclusions of this study were unchanged when subjected to
      sensitivity analyses. CONCLUSION: In this systematic review and meta-analysis of
      prospective studies comparing postoperative outcomes through 90 days of AA vs PA
      in primary THA, patients treated with AA reported less pain, consumed fewer
      narcotics, and reported better hip function. No statistical differences in
      complication rates were detected between AA and PA. Ultimately, the choice of
      surgical approach in primary THA should consider preference and experience of the
      surgeon as well as preference and anatomy of the patient.

PMID- 29195849
TI  - Cementless Posteriorly Stabilized Total Knee Arthroplasty: Seven-Year Minimum
      Follow-Up Report.
AB  - BACKGROUND: The purpose of this study is to evaluate (1) implant survivorship;
      (2) patient outcomes; (3) complications; and to (4) perform a radiographic
      analysis of cementless posteriorly stabilized total knee arthroplasty (TKA)
      patients at a minimum of 7-year follow-up. METHODS: Our original cohort was
      composed of 114 consecutive cementless posteriorly stabilized total knee
      arthroplasties (110 patients) performed by a single surgeon between 2008 and
      2010. Since our original report, 4 (1 bilateral) patients died and 2 were lost to
      follow-up. Therefore, there were 104 patients who had 107 knees available for
      final follow-up. The final cohort included 43 men and 61 women, who had a mean
      age of 69 years (range 47-87) and were followed from 7 to 9 years (mean 8 years).
      Patient outcomes and complications were obtained from electronic medical records.
      Radiographic assessment was done using the Knee Society Radiographic Evaluation
      System. RESULTS: The all-cause survivorship was 98% (95% confidence interval 1.01
      0.96). Since the original report, there has been 1 post-traumatic loosening of
      the tibial baseplate, and 1 revision for instability. There were no femoral
      revisions or patella revisions. The mean Knee Society pain score was 93 points
      (range 80-100) and the function score was 78 points (range 68-95). Excluding
      revisions, there was no evidence of progressive loosening of any implant
      components. CONCLUSION: Based on these 7-year minimum follow-ups, femoral,
      tibial, and patellar cementless hydroxylapatite-coated beaded implants perform
      well at up to 9 years postoperatively and offer surgeons and patients a
      cementless option that may provide long-lasting biological fixation.

PMID- 29195850
TI  - Letter to the Editor on "Serum and Wound Vancomycin Levels Following Intrawound
      Administration in Primary Total Joint Arthroplasty".

PMID- 29195851
TI  - Effect of the Referencing System on the Posterior Condylar Offset and Anterior
      Flange-Bone Contact in Posterior Cruciate-Substituting Total Knee Arthroplasty.
AB  - BACKGROUND: The effect of referencing system on posterior condylar offset (PCO)
      after total knee arthroplasty (TKA) is still controversial. Moreover, there is a
      lack of concern about the anterior flange-bone contact according to the
      referencing system. METHODS: One hundred four TKAs using the anterior referencing
      (AR) system and 107 TKAs using the posterior referencing (PR) system were
      analyzed with 2-year follow-up. The PCO, PCO ratio (PCOR), and contact at the
      anterior flange-bone interface were compared between the 2 groups. The flexion
      and extension gaps and the degree of medial release were measured, and clinical
      outcomes were evaluated. Finally, the correlation between changes in PCO and knee
      flexion angle was analyzed. RESULTS: The mean postoperative PCO and PCOR were
      significantly larger in the PR group than in the AR group. Incomplete contact
      between the anterior flange and anterior femur occurred more frequently in the AR
      group than in the PR group (48.1% vs 13.1%, P < .001). The medial and lateral
      flexion gaps were significantly larger in the AR group than in the PR group. The
      groups showed no differences in soft tissue release, degree of flexion, and
      clinical scores. In both groups, there was no correlation between postoperative
      change of PCO and improvement in flexion. CONCLUSION: The PR system produced
      larger PCO and PCOR, and smaller flexion gap compared to the AR system.
      Additionally, the PR group showed more favorable contact between the anterior
      flange and anterior femur. However, these differences were not related to the
      degree of soft tissue release and clinical outcomes.

PMID- 29195852
TI  - Response to Letter to the Editor on "Arthrofibrosis Associated With Total Knee
      Arthroplasty".

PMID- 29195853
TI  - Erratum to "A Comparative Study on the Long-Term Outcome of Total Knee
      Arthroplasty Performed for Knees Stiff in Extension and Those Stiff in Flexion"
      [Journal of Arthroplasty 32 (2017) 3396-3403].

PMID- 29195854
TI  - Hypothermia in Total Joint Arthroplasty: A Wake-Up Call.
AB  - BACKGROUND: Total joint patients are particularly vulnerable to perioperative
      hypothermia (PH) (combined effects of anesthesia, radiation, and convective heat
      loss from exposed skin surfaces and cool temperatures in the operating room).
      There are limited studies on PH in these patients. METHODS: In a retrospective
      review of 204 patients undergoing primary hip and 179 undergoing primary knee
      replacement surgeries, time and temperature parameters were collected from the
      electronic health records from preoperative and postoperative recovery room
      nursing assessments, intraoperative anesthesia records, and floor nursing notes.
      Basic patient demographic data was recorded. Chi-squared and paired t-tests were
      used to compare between hypothermic and normothermic groups. RESULTS: At the time
      of incision, 60 of 179 (34%) total knee arthroplasty (TKA) patients and 80 of 204
      (39%) total hip arthroplasty (THA) patients were hypothermic. In THA patients,
      65% remained hypothermic for the duration of anesthesia compared to 33% of TKA
      patients. The largest drop in core body temperature in both THA and TKA patients
      occurred between preoperative holding and induction of anesthesia. In THA
      patients, spinal anesthesia had a significantly higher occurrence of PH. No
      significant patient factor was found to increase risk. CONCLUSION: Emphasis on
      preoperative holding protocols, decreasing time from operating room entry to
      incision, and increasing ambient room temperature could reduce risk of
      hypothermia in total joint replacement patients.

PMID- 29195855
TI  - Modeling of the effects of IL-17 and TNF-alpha on endothelial cells and thrombus
      growth.
AB  - Rheumatoid and psoriatic arthritis are chronic inflammatory diseases, with
      massive increase of cardiovascular events (CVE), and contribution of the
      cytokines TNF-alpha and IL-17. Chronic inflammation inside the joint membrane or
      synovium results from the activation of fibroblasts/synoviocytes, and leads to
      the release of cytokines from monocytes (Tumor Necrosis Factor or TNF) and from T
      lymphocytes (Interleukin-17 or IL-17). At the systemic level, the very same
      cytokines affect endothelial cells and vessel wall. We have previously shown
      [1,2] that IL-17 and TNF-alpha, specifically when combined, increase
      procoagulation, decrease anticoagulation and increase platelet aggregation,
      leading to thrombosis. These results are the basis for the models of interactions
      between IL-17 and TNF, and genes expressed by activated endothelial cells. This
      work is devoted to mathematical modeling and numerical simulations of blood
      coagulation and clot growth under the influence of IL-17 and TNF-alpha. We show
      that they can provoke thrombosis, leading to the complete or partial occlusion of
      blood vessels. The regimes of blood coagulation and conditions of occlusion are
      investigated in numerical simulations and in approximate analytical models. The
      results of mathematical modeling allow us to predict thrombosis development for
      an individual patient.

PMID- 29195856
TI  - Codon usage and expression level of human mitochondrial 13 protein coding genes
      across six continents.
AB  - The study of codon usage coupled with phylogenetic analysis is an important tool
      to understand the genetic and evolutionary relationship of a gene. The 13 protein
      coding genes of human mitochondria are involved in electron transport chain for
      the generation of energy currency (ATP). However, no work has yet been reported
      on the codon usage of the mitochondrial protein coding genes across six
      continents. To understand the patterns of codon usage in mitochondrial genes
      across six different continents, we used bioinformatic analyses to analyze the
      protein coding genes. The codon usage bias was low as revealed from high ENC
      value. Correlation between codon usage and GC3 suggested that all the codons
      ending with G/C were positively correlated with GC3 but vice versa for A/T ending
      codons with the exception of ND4L and ND5 genes. Neutrality plot revealed that
      for the genes ATP6, COI, COIII, CYB, ND4 and ND4L, natural selection might have
      played a major role while mutation pressure might have played a dominant role in
      the codon usage bias of ATP8, COII, ND1, ND2, ND3, ND5 and ND6 genes.
      Phylogenetic analysis indicated that evolutionary relationships in each of 13
      protein coding genes of human mitochondria were different across six continents
      and further suggested that geographical distance was an important factor for the
      origin and evolution of 13 protein coding genes of human mitochondria.

PMID- 29195857
TI  - Evaluating acarological risk for exposure to Ixodes scapularis and Ixodes
      scapularis-borne pathogens in recreational and residential settings in Washington
      County, Minnesota.
AB  - The distribution of I. scapularis, the tick vector of the bacteria that cause
      Lyme disease, has been expanding over the last two decades in the north-central
      United States in parallel with increasing incidence of human cases of Lyme
      disease in that region. However, assessments of residential risk for exposure to
      ticks are lacking from this region. Here, we measured the density of host-seeking
      I. scapularis nymphs in two suburban and two rural public recreational sites
      located in Washington County, Minnesota as well as in nearby residential
      properties. We sought to compare tick densities across land use types and to
      identify environmental factors that might impact nymphal density. We also
      assessed the prevalence of infection in the collected ticks with Lyme disease
      spirochetes (Borrelia burgdorferi sensu stricto, B. mayonii), and other I.
      scapularis-borne pathogens including B. miyamotoi, Babesia microti and Anaplasma
      phagocytophilum. Similar to studies from the eastern United States, on
      residential properties, I. scapularis nymphal densities were highest in the
      ecotonal areas between the forest edge and the lawn. Residences with the highest
      densities of nymphs were more likely to have a higher percentage of forest cover,
      log piles, and signs of deer on their property. In recreational areas, we found
      the highest nymphal densities both in the wooded areas next to trails as well as
      on mowed trails. Among the 303 host-seeking I. scapularis nymphs tested for
      pathogens, B. burgdorferi sensu stricto, A. phagocytophilum and B. miyamotoi were
      detected in 42 (13.8%), 14 (4.6%), and 2 (0.6%) nymphs, respectively.

PMID- 29195858
TI  - Phosphate-Binder Use in US Dialysis Patients: Prevalence, Costs, Evidence, and
      Policies.
AB  - Medicare costs for phosphate binders for US dialysis patients and patients with
      chronic kidney disease enrolled in Medicare Part D exceeded $1.5 billion in 2015.
      Previous data have shown that Part D costs for mineral and bone disorder
      medications increased faster than costs for all Part D medications for dialysis
      patients. Despite extensive use of phosphate binders and escalating costs,
      conclusive evidence is lacking that they improve important clinical end points in
      dialysis patients or non-dialysis-dependent patients with chronic kidney disease.
      Using dialysis patient data from the US Renal Data System and laboratory
      information from the Centers for Medicare & Medicaid Services (CMS) CROWNWeb
      data, we update information on trends in phosphate-binder use, calcium and
      phosphorus values, and costs for Medicare-covered dialysis patients. We discuss
      these results in the context of evidence from clinical trials, meta-analyses, and
      observational studies evaluating phosphate-binder efficacy, safety, comparative
      effectiveness, and cost-effectiveness. Based on our analysis, we note a need for
      US Food and Drug Administration guidance regarding clinical evaluation of new
      phosphate binders, and we suggest that it would be in CMS' best interest to fund
      a clinical trial to assess whether lower versus higher phosphate concentrations
      improve hard clinical outcomes, and if so, whether particular phosphate binders
      are superior to placebo or other binders in improving these outcomes.

PMID- 29195859
TI  - ImageJ-based semiautomatic method to analyze senescence in cell culture.
AB  - beta-Galactosidase accumulates in the lysosomes of senescent cells of certain
      tissues. Cell staining with X-gal is a common procedure to detect senescent cells
      in culture. However, the organelle nature of the staining makes automatic count
      impossible, requiring time-consuming manual counting or expensive alternative
      techniques such as flow cytometry to effectively determine the amount of stained
      cells. Here we present an analysis strategy for images of X-gal stained cells
      which can be implemented into a macro for the ImageJ software overcoming some of
      the drawbacks of computational analysis of organelle staining.

PMID- 29195860
TI  - GDF15-From Biomarker to Allostatic Hormone.
AB  - With the identification of its receptor in a highly specific region of the brain,
      interesting issues come to light regarding the normal physiological functions of
      GDF15, a secreted protein long identified as a biomarker of diverse disease
      states.

PMID- 29195861
TI  - The effect of Cytochalasin B and Jasplakinolide on depolymerization of actin
      filaments in goose muscles during postmortem conditioning.
AB  - Breast muscles of twenty-four Eastern Zhejiang White Geese were randomly divided
      into three groups: control, Cytochalasin B (Cyt B) and Jasplakinolide (Jasp)
      treatments during postmortem conditioning. The myofibrillar fraction index (MFI),
      actin filaments and the levels of F-actin, G-actin and actin associated proteins
      (cofilins and tropomodulins) during conditioning were investigated. In control,
      the degraded tropomodulins, increased G-actin and disrupted actin filaments were
      observed at 4 and 7days; the increase of MFI and decrease of F-actin content were
      shown during conditioning. Cyt B treatments accelerated the transformation from F
      actin to G-actin, weakened actin filaments and increased MFI compared to the
      control, while Jasp gained the opposite effect against Cyt B. We concluded that
      depolymerization of actin filaments regulated by tropomodulins contributed to
      myofibrillar fraction during conditioning. This work provided a new pathway of
      tenderization by the depolymerization of actin filaments.

PMID- 29195862
TI  - Spray-dried extract from the Amazonian adaptogenic plant Ampelozizyphus
      amazonicus Ducke (Saracura-mira): Chemical composition and immunomodulatory
      properties.
AB  - Ampelozizyphus amazonicus Ducke is a medicinal plant used in the Amazon region to
      prepare a drink with tonic, immunomodulatory and adaptogenic properties. Due to
      the growing interest in dietary supplements with these properties and, to provide
      a new functional ingredient, barks from A. amazonicus were extracted. The extract
      was spray dried without drying adjuvants, resulting in a powder (SARF), which was
      characterized by its physico-chemical properties and proximate, mineral and
      saponin contents. The SARF saponins were characterized by ultra-high-performance
      liquid chromatography/high resolution accurate mass spectrometry (HPLC-HRMSn)
      analysis. The SARF particles tended to have a spherical shape and a unimodal size
      distribution. The particles also had good rehydration characteristics and high
      saponin content (33%). The effect of SARF on antibody production was
      investigated, and we found that SARF increased the basal levels of anti
      ovalbumin, anti-LPS and anti-dextran IgM antibodies, and the anti-dextran IgG
      antibodies in unimmunized mice. No increase in antibody titers was observed after
      SARF treatment in immunized mice. These results suggest that SARF could be an
      interesting new functional ingredient for food applications or pharmaceutical
      products.

PMID- 29195863
TI  - An investigation into the structure, morphology and thermal properties of
      amylomaize starch-fatty acid complexes prepared at different temperatures.
AB  - Amylomaize (Hylon VII) starch-fatty acid (capric, myristic, palmitic, stearic,
      oleic) complexes prepared at 30, 50 or 70 degrees C were studied using XRD, DSC,
      SEM, TGA and FTIR techniques. XRD diffractograms displayed the typical V-form of
      complexed amylose regardless the temperature of preparing the complexes. The
      degree of crystallinity of the complexes increased while the size of the crystals
      formed decreased as the preparation temperature of the complexes increased. DSC
      thermograms showed that the dissociation temperature of the complexes was
      increased proportionally to the chain length increase of the fatty acid. TGA
      indicated that oleic acid was adequately protected in the form of complexes. SEM
      micrographs showed the presence of crystals of the complexes either in the form
      of spherulites or in the form of lamellae. Enzymatic hydrolysis of the complexes
      led to quantitative recovery of the guest molecules. Hylon VII proved to be a
      suitable prospective complexing agent for the production of complexes of lipids.

PMID- 29195864
TI  - Development of an immobilization system for in situ micronutrients release.
AB  - An immobilization system constituted by coated microcapsules was developed aiming
      at immobilizing probiotic bacteria capable of producing folate and release it in
      a sustained manner into the intestine. Despite no probiotic folate-producers have
      been immobilized so far, the system has been developed with this goal and this
      work reports its stability and ability to release folate under gastro-intestinal
      conditions. Microcapsules were made of alginate with three consecutive coatings
      of poly-l-lysine, sodium alginate and chitosan. Turbidity experiments showed a
      strong electrostatic interaction between these polymers. Fourier transform
      infrared spectroscopy (FTIR) and confocal analysis showed the stability of the
      coating materials when applied on the microcapsules, even after they were
      immersed in solutions simulating conditions in the stomach and small intestine
      (i.e. pH2, 60min and pH7.2, 120min, respectively). Coated microcapsules have an
      average diameter size ranged from 20 and 40MUm, and swelled upon exposure to a
      neutral medium, without dissolution as showed by microscopy analyses. Release
      experiments proved the ability of the coated microcapsules to release folic acid,
      at different rates, depending on the applied coating. Release experiments showed
      that the first coating (E-PLL) is characterized by Fickian diffusion as the main
      release mechanism of folic acid. Fickian rate constant (kF) decreased with the
      number of consequent coatings, reflecting the decrease of predominance of Fick's
      behavior. Results showed that the developed coated microcapsules have suitable
      characteristics for encapsulation of folic acid aiming in situ release in the
      intestine.

PMID- 29195865
TI  - Differentiation of cocoa nibs from distinct origins using comprehensive two
      dimensional gas chromatography and multivariate analysis.
AB  - Headspace solid-phase microextraction (HS-SPME) combined with comprehensive two
      dimensional gas chromatography was used for identification of volatiles compounds
      responsible for differentiation between cocoa nibs from Brazil and Ivory Coast.
      The unfolded GC*GC with Flame Ionization Detector (FID) chromatograms were first
      aligned using the correlation optimization warping (COW) algorithm and
      normalized. After that, Fisher ratio was calculated for each variable, and a
      threshold value was chosen to select the variables that best promote a separation
      of nibs samples from different sources in a principal component analysis (PCA)
      model. To identify the relevant compounds for the separation, representative
      samples of each source were analyzed in the same conditions by GC*GC with
      detection by quadrupole mass spectrometry. Finally, the average peak volumes for
      each key compound obtained for both classes were compared using a Student t-test
      and it was possible to identify 15 volatile compounds responsible for
      differentiation between cocoa nibs from Brazil and Ivory Coast.

PMID- 29195866
TI  - beta-Carotene-loaded nanostructured lipid carriers produced by solvent
      displacement method.
AB  - Tristearin solid lipid nanoparticles and tristearin/high oleic sunflower oil
      nanostructured lipid carriers were produced by solvent displacement method. All
      conditions allowed forming polydisperse particles within nanometric range and the
      presence of high oleic sunflower oil did not affect the particles mean size.
      Nevertheless, incorporation of beta-carotene reduced the particles
      polydispersity. Thermograms of solid lipid nanoparticles and nanostructured lipid
      carriers showed that sunflower oil generated a crystal order disturbance, since
      nanoparticles with less-organized lipid matrix were produced. Nanostructured
      lipid carriers exhibited an improvement of beta-carotene loading capacity when
      compared with solid lipid nanoparticles, which enhanced with the increasing of
      high oleic sunflower oil content. Although total beta-carotene degradation was
      similar for all systems, color analysis showed that the degradation of
      encapsulated beta-carotene was lower for high sunflower oil content.
      Nanostructured lipid carriers exhibited advantages over the solid lipid
      nanoparticles, such as enhanced drug loading capacity and prevention of drug
      expulsion, which makes this a versatile delivery system for food applications.

PMID- 29195867
TI  - Lactococcus lactis subsp. cremoris strain JFR1 attenuates Salmonella adhesion to
      human intestinal cells in vitro.
AB  - Lactococcus lactis subsp. cremoris JFR1 has been studied in reduced fat cheese
      due to its ability to produce exopolysaccharides (EPS) in situ, contributing to
      improved textural and organoleptic properties. In this study, the effect of
      strain JFR1 on virulence gene expression and attachment of Salmonella to HT-29
      human colon carcinoma cells was investigated. Overnight cultures of L. lactis
      subsp. cremoris JFR1 containing EPS, grown in M17 media with 0.5% glucose
      supplementation, decreased attachment as well as down regulated virulence gene
      expression in Salmonella enterica subsp. enterica when tested on HT-29 cells.
      However, EPS isolated from milk fermented with L. lactis subsp. cremoris JFR1 did
      not affect Salmonella virulence gene expression or attachment to HT-29 cells.
      These results suggest that EPS does not contribute to the attachment of
      Salmonella to human intestinal cells. However, the possibility that the isolation
      process may have affected the structural features of EPS cannot be ruled out.

PMID- 29195868
TI  - Mitigation strategies of acrylamide, furans, heterocyclic amines and browning
      during the Maillard reaction in foods.
AB  - The Maillard reaction (MR) occurs widely during food manufacture and storage,
      through controlled or uncontrolled pathways. Its consequences are ambiguous
      depending on the nature and processing of the food products. The MR is often used
      by food manufacturer to develop appealing aromas, colour or texture in food
      products (cereal based food, coffee, meat...). However, despite some positive
      aspects, the MR could decrease the nutritional value of food, generate
      potentially harmful compounds (e.g. acrylamide, furans, heterocyclic amines) or
      modify aroma or colour although it is not desired (milk, fruit juice). This paper
      presents a review of the different solutions available to control or moderate the
      MR in various food products from preventive to removal methods. A brief reminder
      of the role and influence of the MR on food quality and safety is also provided.

PMID- 29195869
TI  - Lactoferrin-based nanoparticles as a vehicle for iron in food applications -
      Development and release profile.
AB  - This study aims at developing and characterizing bovine lactoferrin (bLf)
      nanoparticles as an iron carrier. bLf nanoparticles were characterized in terms
      of size, polydispersity index (PdI), electric charge (zeta-potential),
      morphology, structure and stability over time. Subsequently, iron release
      experiments were performed at different pH values (2.0 and 7.0) at 37 degrees C,
      in order to understand the release mechanism. bLf (0.2%, w/v) nanoparticles were
      successfully produced by thermal gelation (75 degrees C for 20min). bLf
      nanoparticles with 35mM FeCl3 showed an iron binding efficiency value of
      approximately 20%. The nanoparticles were stable (i.e. no significant variation
      of size and PdI of the nanoparticles) for 76days at 4 degrees C and showed to be
      stable between 4 and 60 degrees C and pH2 and 11. Release experiments at pH2
      showed that iron release could be described by the linear superposition model
      (explained by Fick and relaxation phenomenon). On the contrary, the release
      mechanism at pH7 cannot be described by either Fick or polymer relaxation
      behaviour. In general, results suggested that bLf nanoparticles could be used as
      an iron delivery system for future food applications.

PMID- 29195870
TI  - Influence of reuterin-producing Lactobacillus reuteri coupled with glycerol on
      biochemical, physical and sensory properties of semi-hard ewe milk cheese.
AB  - The biochemical, physical and sensory characteristics of ewe milk cheeses made
      with reuterin-producing Lactobacillus reuteri and glycerol (substrate for
      reuterin production) were assessed. Cheese made with lactococci starter (CTRL),
      cheese made with starter and L. reuteri (SLR), and cheese made with starter, L.
      reuteri and 30mM glycerol (SLR-G) were manufactured. L. reuteri reached counts
      above 7logcfu/g on day 1. Lactococci survival was enhanced in SLR cheese without
      affecting cheese pH, dry matter, proteolysis, concentration of most free amino
      acids (FAA), textural and most color parameters, or sensory characteristics. In
      situ production of reuterin by L. reuteri was only detected in SLR-G cheese,
      decreasing LAB counts although acidification remained unaffected. SLR-G cheese
      showed higher values of cell free aminopeptidase activity, overall proteolysis
      and FAA, particularly glutamic acid, than CTRL and SLR cheeses. The addition of
      L. reuteri-glycerol resulted in lower hardness and elasticity values in SLR-G
      cheese and influenced its L*, a* and b* color parameters. However, these changes,
      which were detected by instrumental analysis, did not affect the sensory scores
      for texture and color quality of SLR-G cheese, and it received the highest scores
      for taste quality. Our results suggest that L. reuteri-glycerol may provide a
      suitable system to release the antimicrobial reuterin in cheese without affecting
      negatively its sensory characteristics.

PMID- 29195871
TI  - 3-Chlorotyrosine formation in ready-to-eat vegetables due to hypochlorite
      treatment and its dietary exposure and risk assessment.
AB  - Washing of iceberg lettuce with HOCl solutions in concentrations ranging from
      1.41 to 141mg/L resulted in 0.69 to 2.05MUg3-chlorotyrosine/g vegetable. As also
      six commercial ready-to-eat iceberg lettuces from different producers contained 3
      chlorotyrosine from 1.00 to 2.24MUg/g vegetable, a total of 122 ready-to-eat
      vegetable samples purchased in Belgian supermarkets were further screened for
      their 3-chlorotyrosine content. 3-chlorotyrosine was detected above the detection
      limit (0.19MUg/g sample) in 97, 24 and 14% of the lettuce mixes, vegetable mixes
      and frozen vegetables, respectively. In combination with consumption data of
      ready-to-eat vegetables by Belgian and Spanish consumers, a quantitative exposure
      assessment was performed, exemplifying a lower and higher ready-to-eat vegetables
      consuming population. Exposure to 3-chlorotyrosine from the frozen vegetables and
      vegetable mixes was lower compared to the lettuce mixes due to the combination of
      lower contamination and lower consumption. 3-chlorotyrosine exposure via lettuce
      mixes could be considered as a public health concern, especially in higher
      consuming populations represented by the Spanish population, with 17% of
      consumers (>4.2 million people) and 8.5% of the total population (>2,6 million
      people) exceeding the threshold of toxicological concern.

PMID- 29195872
TI  - Multivariate analyses of a wide selection of orange varieties based on carotenoid
      contents, color and in vitro antioxidant capacity.
AB  - Carotenoids, color and in vitro antioxidant capacity were analyzed in twenty-two
      genotypes of oranges produced in Spain in two consecutive seasons. The colorless
      carotenoids phytoene and phytofluene were also analyzed. An important influence
      of the genotype on the carotenoid profile was observed. In most genotypes, such
      profile was characterized by the predominance of xanthophylls (82.7-93.0%),
      except in Cara Cara, with a higher proportion of carotenes (around 70.0%). beta
      cryptoxanthin was the predominant carotenoid in Rohde late and Ambersweet. The
      samples with the lowest carotenoid contents were the ones exhibiting the lowest
      Trolox Equivalent Antioxidant Capacity (TEAC) and vice versa. A formula obtained
      by multiple regression is proposed to estimate the TEAC value from the carotenoid
      content. No significant correlation between TEAC values and color coordinates
      were obtained, suggesting that color parameters are not good predictors of TEAC
      values. Lastly, the samples could be classify with a high rate of success (>90%)
      by Linear Discriminant Analysis based on color and carotenoids.

PMID- 29195873
TI  - Kunitz trypsin inhibitor in addition to Bowman-Birk inhibitor influence stability
      of lunasin against pepsin-pancreatin hydrolysis.
AB  - Soybean contains several biologically active components and one of this belongs
      to the bioactive peptide group. The objectives of this study were to produce
      different lunasin-enriched preparations (LEP) and determine the effect of Bowman
      Birk inhibitor (BBI) and Kunitz trypsin inhibitor (KTI) concentrations on the
      stability of lunasin against pepsin-pancreatin hydrolysis (PPH). In addition, the
      effect of KTI mutation on lunasin stability against PPH was determined. LEP were
      produced by calcium and pH precipitation methods of 30% aqueous ethanol extract
      from defatted soybean flour. LEP, lunasin-enriched commercially available
      products and KTI control and mutant flours underwent PPH and samples were taken
      after pepsin and pepsin-pancreatin hydrolysis. The concentrations of BBI, KTI,
      and lunasin all decreased after hydrolysis, but they had varying results. BBI
      concentration ranged from 167.5 to 655.8MUg/g pre-hydrolysis and 171.5 to
      250.1MUg/g after hydrolysis. KTI concentrations ranged from 0.3 to 122.3MUg/g pre
      hydrolysis and 9.0 to 18.7MUg/g after hydrolysis. Lunasin concentrations ranged
      from 8.5 to 71.0MUg/g pre-hydrolysis and 4.0 to 13.2MUg/g after hydrolysis. In
      all products tested, lunasin concentration after PPH significantly correlated
      with BBI and KTI concentrations. Mutation in two KTI isoforms led to a lower
      concentration of lunasin after PPH. This is the first report on the potential
      role of KTI in lunasin stability against PPH and must be considered in designing
      lunasin-enriched products that could potentially survive digestion after oral
      ingestion.

PMID- 29195874
TI  - Development of an in vitro mechanical gastric system (IMGS) with realistic
      peristalsis to assess lipid digestibility.
AB  - A new in vitro mechanical gastric system (IMGS) was fabricated which
      incorporates: a J-shaped stomach, a mechanical system with realistic peristaltic
      frequency and force magnitude, and a reproduction of the gastric pH curve. To
      evaluate the impact of a more realistic gastric peristalsis on the intestinal
      lipolysis of protein-stabilized O/W emulsions, the emulsions were subjected to
      two different in vitro digestion methodologies: (i) gastric digestion in the IMGS
      and intestinal digestion in a stirred beaker (SB), and (ii) gastric and
      intestinal digestion assays carried out in SBs. At the end of the intestinal
      digestion, the total amount of free fatty acids released was significantly higher
      for the first methodology (IMGS-SB) in comparison with the second one (27.5% vs.
      23.0%), probably due to the higher physical instability induced by the IMGS in
      the gastric contents. These results reaffirm that O/W emulsion stability plays a
      crucial role in controlling the final extent of lipolysis of this kind of food
      grade emulsions.

PMID- 29195876
TI  - Front of package symbols as a tool to promote healthier food choices in Slovenia:
      Accompanying explanatory claim can considerably influence the consumer's
      preferences.
AB  - Many nutrition and/or health symbols were introduced in different countries in
      the past years and Slovenia is no exception. The objective of our study was to
      examine familiarity with and perception of the Protective Food symbol (PF symbol)
      in Slovenia and to investigate consumers' associations related to the symbol, and
      the influence of symbols' appearance on their preferences. The study was
      conducted through online questionnaire with incorporated word-association tasks
      and conjoint analysis; GfK consumer panel and social media (Facebook) were used
      for recruitment of Slovenian adults (n=1050; 534 men, 516 women). The majority
      (78%) of the participants reported they had previously seen the PF symbol, and
      64% declared familiarity with it. Familiarity was verified using a word
      association task in which we analysed the nature of the symbol's description,
      distinguishing the description of symbol's visual appearance or its meaning. In
      this task, 73% of the participants described the symbol's meaning with reference
      to health or a healthy lifestyle, confirming their familiarity with it. Women and
      those responsible for grocery shopping were significantly more familiar with the
      symbol. The impact of the symbol's appearance on consumers' preferences was
      investigated using conjoint analysis consisting of two attributes - three
      different symbols found on foods in Slovenia (PF symbol, Choices Programme symbol
      and Keyhole symbol), and accompanying worded claims. Although worded claims had
      less relative importance (29.5%) than the symbols (70.5%), we show that careful
      choice of the wording can affect consumers' preferences considerably. The lowest
      part-worth utility was observed without an accompanying claim, and the highest
      for the claim directly communicating health ("Protects your health"). The fact
      that most participants are well familiar with the PF symbol indicates the
      symbol's potential to promote healthier food choices, which could be further
      improved by an accompanying worded claim that clearly describes its meaning. In
      addition, the use of Facebook ads is shown to be a useful alternative recruitment
      method for research with consumers.

PMID- 29195875
TI  - Exploring the protective effects of calcium-containing carrier against drying
      induced cellular injuries of probiotics using single droplet drying technique.
AB  - Protective carriers that encapsulate probiotics in spray drying could improve the
      survival ratio of dried cells through different mechanisms. Unveiling the
      protective mechanism of each carrier will contribute to a rational design of high
      performance carrier formulation. This study utilized single droplet drying (SDD)
      technique to investigate the effects of calcium cation in varied carrier
      formulation. Inactivation histories of Lactobacillus rhamnosus GG (LGG) in
      different carriers were compared, and cellular injury history of probiotics
      during droplet drying was studied for the first time. Adding 1mM CaCl2 to lactose
      carrier protected cell viability, mitigated cellular injuries, and enhanced
      regrowth capability as drying progressed, demonstrating the positive effect of
      Ca2+ with possible mechanism of stabilizing sub-cellular structures. At later
      drying stages, cell survival in Lac/Ca carrier was increased by 0.5-1.5 log on
      selective media compared to lactose carrier. Supplementing calcium-binding agents
      lowered the protective effect, shortening the initiation of rapid cell
      inactivation down to 120s of drying. Adding CaCl2 to trehalose carrier barely
      improved cell survival, indicating that the protective effect could be influenced
      by carrier formulation. Pure trehalose carrier exerted excellent protection on
      LGG, supporting cells to regrow in liquid rich medium even after 180s of drying.
      The protection of trehalose may stem from stabilization of sub-cellular
      structures, which possibly overlap the effect of Ca2+. The findings suggested
      that high performance carrier formulation might be developed by combining carrier
      materials with different protective mechanisms, for maximizing the survival of
      active dry probiotics in industrial spray drying operation.

PMID- 29195877
TI  - Does a time constraint modify results from rating-based conjoint analysis? Case
      study with orange/pomegranate juice bottles.
AB  - People do not usually process all the available information on packages for
      making their food choices and rely on heuristics for making their decisions,
      particularly when having limited time. However, in most consumer studies
      encourage participants to invest a lot of time for making their choices.
      Therefore, imposing a time-constraint in consumer studies may increase their
      ecological validity. In this context, the aim of the present work was to evaluate
      the influence of a time-constraint on consumer evaluation of pomegranate/orange
      juice bottles using rating-based conjoint task. A consumer study with 100
      participants was carried out, in which they had to evaluate 16 pomegranate/orange
      fruit juice bottles, differing in bottle design, front-of-pack nutritional
      information, nutrition claim and processing claim, and to rate their intention to
      purchase. Half of the participants evaluated the bottle images without time
      constraint and the other half had a time-constraint of 3s for evaluating each
      image. Eye-movements were recorded during the evaluation. Results showed that
      time-constraint when evaluating intention to purchase did not largely modify the
      way in which consumers visually processed bottle images. Regardless of the
      experimental condition (with or without time constraint), they tended to evaluate
      the same product characteristics and to give them the same relative importance.
      However, a trend towards a more superficial evaluation of the bottles that
      skipped complex information was observed. Regarding the influence of product
      characteristics on consumer intention to purchase, bottle design was the variable
      with the largest relative importance in both conditions, overriding the influence
      of nutritional or processing characteristics, which stresses the importance of
      graphic design in shaping consumer perception.

PMID- 29195878
TI  - Probiotic-loaded microcapsule system for human in situ folate production:
      Encapsulation and system validation.
AB  - This study focused on the use of a new system, an alginate|E-poly-l
      lysine|alginate|chitosan microcapsule (APACM), able to immobilize a folate
      producing probiotic, Lactococcus lactis ssp. cremoris (LLC), which provides a new
      approach to the utilization of capsules and probiotics for in situ production of
      vitamins. LLC is able to produce 95.25+/-26MUg.L-1 of folate, during 10h, and was
      encapsulated in the APACM. APACM proved its capacity to protect LLC against the
      harsh conditions of a simulated digestion maintaining a viable concentration of
      6logCFU.mL-1of LLC. A nutrients exchange capacity test, was performed using
      Lactobacillus plantarum UM7, a high lactic acid producer was used here to avoid
      false negative results. The production and release of 2g.L-1 of lactic acid was
      achieved through encapsulation of L. plantarum, after 20h. The adhesion of APACM
      to epithelial cells was also quantified, yielding 38% and 33% of capsules adhered
      to HT-29 cells and Caco-2 cells, respectively.

PMID- 29195879
TI  - Role of mono- and oligosaccharides from FOS as stabilizing agents during freeze
      drying and storage of Lactobacillus delbrueckii subsp. bulgaricus.
AB  - The aim of this work was to assess the role of mono- and oligosaccharides present
      in fructo-oligosaccharides (FOS) mixtures as protective agents during freeze
      drying and storage of Lactobacillus delbrueckii subsp. bulgaricus CIDCA 333.
      Different FOS mixtures were enzymatically obtained from sucrose and further
      purified by removing the monosaccharides produced as secondary products. Their
      glass transition temperatures (Tg) were determined at 11, 22 and 33% relative
      humidity (RH). Bacterial cultures were freeze-dried in the presence of 20% w/v
      solutions of the studied FOS. Their protective effect during freeze-drying was
      assessed by bacterial plate counting, and by determining the lag time from growth
      kinetics and the uptake of propidium iodide (PI). Plate counting during bacterial
      storage at 4 degrees C, and 11, 22 and 33% RH for 80days completed this rational
      analysis of the protective effect of FOS. Purification of FOS led to an increase
      of Tg in all the conditions assayed. Microorganisms freeze-dried in the presence
      of non-purified FOS were those with the shortest lag times. Bacteria freeze-dried
      with pure or commercial FOS (92% of total FOS) showed larger lag times (8.9
      12.6h). The cultivability of microorganisms freeze-dried with non-purified FOS
      and with sucrose was not significantly different from that of bacteria before
      freeze-drying (8.74+/-0.14logCFU/mL). Pure or commercial FOS were less efficient
      in protecting bacteria during freeze-drying. All the protectants prevented
      membrane damage. The cultivability of bacteria freeze-dried with FOS decayed
      <1logarithmicunit after 80days of storage at 11% RH. When storing at 22 and 33%
      RH, pure and commercial FOS were those that best protected bacteria, and FOS
      containing monosaccharides were less efficient. The effect of FOS on bacterial
      protection is the result of a balance between monosaccharides, sucrose and larger
      FOS in the mixtures: the smallest sugars are more efficient in protecting lipid
      membranes, and the larger ones favor the formation of vitreous states.

PMID- 29195880
TI  - Technological, rheological and sensory characterizations of a yogurt containing
      an exopolysaccharide extract from Lactobacillus fermentum Lf2, a new food
      additive.
AB  - Lactobacillus fermentum Lf2, an autochthonous strain isolated as a non starter
      culture in Cremoso cheese, produces high EPS levels (~1g/L) in optimized
      conditions (SDM broth, pH6.0, 30 degrees C, 72h). Technological (texture profile
      and rheological analysis) and sensory properties of non-fat yogurts with 300 and
      600mg EPS/L were studied at 3 and 25days after manufacture. Yogurts with
      different EPS concentrations showed higher hardness values than the control group
      at both periods of time, being the only significant difference that remained
      stable during time. The consistency index was also higher for the treated samples
      at both times evaluated, being significantly different for samples with 300mg/L
      of EPS extract, while the flow behavior index was lower for EPS-added yogurts.
      The thixotropic index was lower (P<0.05) for samples with the highest EPS extract
      concentration at the end of the storage time. Regarding the sensory analysis,
      those yogurts with 600mg/L of EPS extract presented the highest values of
      consistency at 3days of storage. No considerable differences for defects (milk
      powder, acid, bitter and cooked milk flavors) were perceived between treated and
      control samples at both times evaluated. Syneresis was also studied and samples
      with 600mg/L of EPS extract presented the lowest syneresis values at 25days of
      storage, which considerably decreased with the time of storage. In conclusion,
      the EPS from L. fermentum Lf2, used as an additive, provided yogurt with creamy
      consistency and increased hardness, without the presence of unwanted defects and
      improving the water holding capacity of the product. All the analysis done showed
      the potential of this extract to be used as a technofunctional natural
      ingredient, and it should be considered its positive impact on health, according
      to previous studies.

PMID- 29195881
TI  - Identification, characterization, and initial epitope mapping of pine nut
      allergen Pin k 2.
AB  - The aims of this study were to predict, identify and characterize pine nut
      allergens. Korean pine (Pinus koraiensis) vicilin was predicted to be a pine nut
      allergen. Recombinant Korean pine vicilin was expressed in E. coli and purified.
      Natural Korean pine vicilin isolated from pine nuts (which displayed multiple
      bands in SDS-gels due to posttranslational digestion) and its full length
      recombinant counterpart were used to test whether it is a food allergen. The
      recognition of the protein (and its fragments) by patient serum IgE was analyzed
      by Western blot. The study included fourteen patients diagnosed with clinical
      pine nut allergy. Twenty nine percent of the patient sera recognized both the
      natural and recombinant pine nut vicilin, indicating that Korean pine vicilin is
      a bona fide food allergen. The serum recognition patterns of the naturally
      occurring protein fragments suggested that some of linear IgE epitopes may be
      mapped to the fragment boundaries. The chemical and thermal stability of the
      recombinant protein was investigated. It underwent a thermal transition with a
      Tm=76.6 degrees C. The transition was accompanied by an increase in the amplitude
      of the circular dichroism signal at 220nm. Urea induced unfolding of the
      recombinant protein had a Cm of 4.6M.

PMID- 29195882
TI  - Assessment of antioxidant activity, lipid profile, general biochemical and immune
      system responses of Wistar rats fed with dairy dessert containing Lactobacillus
      acidophilus La-5.
AB  - The viability and survival of Lactobacillus acidophilus La5 under in vitro
      simulated gastrointestinal in probiotic dairy dessert was assessed. In addition,
      the effects of regular consumption of the dessert (5g/day) on the lipid profile,
      immune system, and antioxidant/biochemical status of Wistar rats were also
      evaluated after 2weeks of treatment. Adequate counts of L. acidophilus La-5 were
      observed regards the viability and gastrointestinal conditions. The probiotic
      dairy dessert was efficient in reducing the LDL-cholesterol, triacylglycerol and
      increased the HDL-cholesterol in serum. Aspartate amino transferase, alanine
      aminotransferase, total protein, albumin, heat shock proteins, immune system
      responses, and blood-cells counts (monocyte, lymphocyte, neutrophil and
      leucocyte) were not affected (p>0.05) after 15days of treatment. Overall, the
      probiotic dairy dessert may be a viable alternative to enhance the blood lipid
      profile and could be used to improve the antioxidant defenses.

PMID- 29195883
TI  - Metabolic profile comparison of fruit juice from certified sweet cherry trees
      (Prunus avium L.) of Ferrovia and Giorgia cultivars: A preliminary study.
AB  - Sweet cherries are widely appreciated for fresh consumption as well as for
      production of juices, jams, jelly fruits and alcoholic beverages. The sweet
      cherry intake (as fresh fruit and related products) is extensively encouraged for
      their taste and nutritional qualities, due to the presence of water-soluble (C,
      B) and fat-soluble (A, E and K) vitamins, carotenoids, polyphenols and minerals,
      as well as glucose and fructose. However the market often endorses the
      consumption of a particular sweet cherry cultivar (as for most of vegetables)
      essentially for organoleptic and/or external appearance rather than nutraceutical
      qualities. In order to evaluate the potential difference in the nutritional
      quality of fruits, 56 sweet cherry juice samples from certified trees (Prunus
      avium L.) of two cultivars (30 from Ferrovia and 26 from Giorgia), grown in the
      same pedoclimatic Apulian region, were analyzed by 1H NMR spectroscopy and
      Multivariate Analysis (MVA). Interestingly, despite the usually lower commercial
      value with respect to the Ferrovia, Giorgia cultivar shows higher content of
      malic acid and phenolic compounds with important well known nutraceutical
      properties such as antioxidant activity and stimulating metabolism.

PMID- 29195884
TI  - Study of the polysemic term of minerality in wine: Segmentation of consumers
      based on their textual responses to an open-ended survey.
AB  - Over the past 20years, the word "minerality" has been increasingly used in the
      description of wines. However, a precise definition of the concept of minerality
      appears to be inexistent, and no consensual meaning, even among wine
      professionals, can be identified. Although this word usage seems to spread out
      from wine professionals to consumers, research on what consumers assume about
      minerality is scarce. This paper aims to study the various concepts about
      minerality held by consumers by using an open-ended questionnaire. A total of
      1697 French-speaking consumers responded to an online survey and their free
      answers were analysed using statistical textual methods. The clustering around
      latent variables (CLV) method was used, taking into account both the lexicon used
      and the personal characteristics of consumers to classify them. Word
      associativities were then computed by means of renormalized Markov
      associativities, generating textual networks associated to each group, as well as
      to personal characteristics of the consumers. Typically, the most inexperienced
      consumers confess to have never heard about minerality in wine. Then, young
      women, also endowed with little wine competences, mainly associate minerality to
      mineral ions as those found in bottled water. Slightly older consumers embed the
      concept of minerality into the idea of terroir. Finally, the most experienced
      consumers refer to sensory perceptions such as gunflint or acidity. Those
      findings are consistent with a lexical innovation process, diffusing from wine
      professionals to consumers, referring to the mineral kingdom (as opposed to
      animal or vegetal), and aiming to stress that the style of their wines has
      changed towards more subtlety. Beyond the specific minerality issue investigated
      in this paper, the methodology (CLV approach used in conjunction with
      renormalized Markov associativities) demonstrates its ability to generate
      informative clusters of textual networks, highlighting the cores of prototypical
      sentences, and apt to investigate the meaning of new concepts.

PMID- 29195885
TI  - Differentiation of commercial ground beef products and correlation between
      metabolites and sensory attributes: A metabolomic approach.
AB  - Three traditional grinds (commodity products) and 7 non-traditional grinds
      (branded products) were obtained to investigate the metabolites in ground beef
      associated with beef flavor or off-flavor. Three packaging methods were used:
      traditional overwrap, modified atmosphere package, and clear plastic retail chub.
      Samples were collected for sensory evaluation and metabolic profiling utilizing
      LC/MS. Principal component analysis was conducted for classification of grind
      source or packaging method. Partial least squares regression was applied to
      investigate the relationship between metabolic data and sensory data. Grass-fed
      beef and natural beef products were clearly separated from the other grinds. A
      total of 576 metabolites were registered. Thirty-three compounds were selected as
      the most important ones differentiating beef grinds. Twenty-two compounds were
      selected as the most important ones associated with beef flavor and off-flavor.
      In conclusion, metabolomic approach was effective to determine the most important
      compounds associated with certain quality characteristics of beef.

PMID- 29195886
TI  - LC-MSn study of the chemical transformations of hydroxycinnamates during yerba
      mate (Ilex paraguariensis) tea brewing.
AB  - Yerba mate is one of the most popular beverages in South American countries and
      its consumption is associated with a wide array of health effects. In this study,
      we used advanced HPLC-ESI-MSn and HPLC-ESI-HRMS methods for the identification
      and characterization of hydroxycinnamates and their derivatives formed during the
      brewing process of yerba mate. We report on the hydroxylation of the
      hydroxycinnamates cinnamoyl substituent by conjugate addition of water to form 3
      hydroxy-dihydrocinnamic acid derivatives using a series of model compounds,
      including caffeoylglucoses, dicaffeoylquinic acids, methyl caffeoylquinate and
      mono caffeoylquinic acids. The regiochemistry of conjugate addition was
      determined by targeted tandem MS experiments performed on authentic standards. It
      was interesting to note that hydroxylation of hydroxycinnamates produced cis and
      acyl-migration isomers, which is in line with previously reported data.

PMID- 29195887
TI  - Antioxidant capacity of cocoa beans and chocolate assessed by FTIR.
AB  - The total antioxidant capacity (TAC) and total phenolic compounds (TPC) of cocoa
      beans and chocolate produced from spontaneous and inoculated fermentations of
      different cocoa varieties were evaluated. Fourier transform infrared spectroscopy
      (FTIR), as well as conventional methods: 2,2-diphenyl-1-picrylhydrazyl (DPPH) and
      2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), was used to
      determine TAC and TPC. Chocolate showed higher (p<0.05) TPC (47.17-57.16mgGAE/g)
      and TAC (1.66-2.33mMTE/g and 8.86-11.35mMTE/g as measured by DPPH and ABTS,
      respectively) than cocoa beans (6.30-26.05mgGAE/g, 0.24-1.17mMTE/g and 1.29
      4.83mMTE/g for TPC, DPPH and ABTS, respectively). Partial least square (PLS)
      model for infrared data showed a good calibration coefficient (R2cal>0.94),
      indicating that the FTIR technique represents a fast and reliable tool to
      evaluate TPC and TAC in cocoa beans and chocolate.

PMID- 29195888
TI  - Formulation and stability assessment of ergocalciferol loaded oil-in-water
      nanoemulsions: Insights of emulsifiers effect on stabilization mechanism.
AB  - In the study, we investigated the effect of emulsifiers with different
      stabilizing mechanisms on the formulation and stability of ergocalciferol loaded
      oil-in-water (O/W) emulsions. O/W emulsion stabilized by modified lecithin (ML;
      electrostatic stabilization), sodium caseinate (SC; electrosteric stabilization)
      or decaglycerol monooleate (MO-7S; steric stabilization) were formulated using
      high-pressure homogenization. The Sauter mean diameter (d3,2) of emulsions
      produced by ML, SC and MO-7S were 126+/-1, 127+/-4 and 138+/-3nm, respectively.
      The stability of resulting emulsions was evaluated when they exposed to different
      environmental stresses and during 30days of storage at 25 and 55 degrees C.
      Results showed that the emulsions prepared by MO-7S or ML were stable against a
      wide range of pH (2-8), while SC-stabilized emulsions showed instability with
      extensive droplet aggregation at pH4 or and 5. Only ML-stabilized emulsions
      showed droplet growth due to coalescence when treated at high NaCl concentration
      (300-500mM). In the absence of glucose, SC-stabilized O/W emulsions showed better
      freeze-thaw stability, in comparison to those formed with ML or MO-7S
      emulsifiers. The emulsion produced by ML was found to be stable to droplet
      aggregation at heating temperatures (80-120 degrees C) for 1h. All the O/W
      emulsions stored at 25 degrees C showed good physical and chemical stability.
      However, the chemical stability of ergocalciferol in emulsion system decreased in
      order of ML>MO-7S?SC during storage at 55 degrees C for a period of 30days. These
      findings provide valuable information for the development of nanoemulsion-based
      delivery system applied in food and beverage products.

PMID- 29195889
TI  - Intracellular ROS scavenging and antioxidant enzyme regulating capacities of corn
      gluten meal-derived antioxidant peptides in HepG2 cells.
AB  - The objective of this study was to investigate the intracellular reactive oxygen
      species (ROS) scavenging activities and antioxidant enzyme regulating capacities
      of corn gluten peptide fractions (CPFs) in HepG2 cells. A cellular antioxidant
      activity (CAA) assay was used to assess their antioxidant activities and revealed
      that both CPF1 (molecular weight <1kDa) and CPF2 (molecular weight between 1 and
      3kDa) exhibited high cellular antioxidant activities with EC50 values of 2.85+/
      0.19mg/mL and 5.05+/-0.32mg/mL, respectively. Both CPFs also exhibited
      cytoprotective effects and intracellular ROS scavenging activities in HepG2 cells
      subjected to oxidative stress by oxidation with H2O2. In addition, at
      concentrations of 2.50mg/mL, the CPFs increased the activity levels of superoxide
      dismutase (SOD), catalase (CAT), and glutathione reductase (GR), as well as the
      total glutathione (GSH) levels in oxidized HepG2 cells (from 86.54% to 114.14%
      (CPF1) or 109.72% (CPF2) for SOD activity; from 71.91% to 107.64% (CPF1) or
      106.50% (CPF2) for CAT activity; from 70.52% to 103.01% (CPF1) or 104.10% (CPF2)
      for GR activity; and from 81.39% to 114.00% (CPF1) or 108.82% (CPF2) for total
      GSH levels). These results suggested that both CPF1 and CPF2 exhibited positive
      effects on the activities of the intracellular antioxidant enzymes SOD, CAT and
      GR, as well as on the total GSH levels in HepG2 cells under conditions of
      oxidative stress. Furthermore, size exclusion gel chromatography and MALDI
      TOF/TOF mass spectrometry revealed that the molecular weights of the antioxidant
      peptides in CPF1 were between 500Da to 900Da, and a novel antioxidant peptide
      consisting of GLLLPH (Gly-Leu-Leu-Leu-Pro-His) was identified in CPF1.

PMID- 29195890
TI  - Probiotics and their potential applications in active edible films and coatings.
AB  - The global market for probiotics has been increasingly growing in recent years
      guided by the rising consumers' demand for healthy diets and wellness. This has
      caused food industries to develop new probiotic-containing food products as well
      as researchers to study specific characteristics of probiotics as well as their
      effects on human health. Probiotics are defined as live microorganisms that
      confer a health benefit to the host when administered in adequate quantities.
      Probiotics have been added to several food products as well as incorporated into
      biopolymeric matrices to develop active food packaging as an alternative method
      for controlling foodborne microorganisms, improving food safety, and providing
      health benefits. This review includes definition of probiotics, description of
      their effects on human health, discussion on their applications in edible
      biopolymeric matrices to develop active edible films and coatings, as well as the
      probiotics-related legislation.

PMID- 29195891
TI  - Biochemical fate of vicilin storage protein during fermentation and drying of
      cocoa beans.
AB  - Key cocoa-specific aroma precursors are generated during the fermentation of
      cocoa beans via the proteolysis of the vicilin-like globulin. Previous studies
      had shown that degradation of this particular 566 amino acid-long storage protein
      leads to three distinct subunits with different molecular masses. Although
      oligopeptides generated from the proteolysis of vicilin-like globulin have been
      studied previously, changes occurring to vicilin at different stages of
      fermentation have not yet been explored in detail. The aim of this study was to
      investigate the fate of vicilin protein from the non-fermented stage up to the
      dried cocoa beans. Our results showed a remarkable shift in the electrophoretic
      mobility of vicilin towards higher pI during the onset of fermentation. The pI
      shifted subunit was found susceptible to further degradation into a lower
      molecular-weight vicilin subunit. The observed pI shift correlated with, but did
      not depend on protein phosphorylation. Glycosylation of some but not all vicilin
      subunits occurred at different stages of the fermentation process. Peptides
      generated from vicilin throughout fermentation were analyzed by UHPLC-ESI-MS/MS
      revealing an initial increase and subsequent decrease in the diversity of
      peptides with an increasing degree of fermentation. We furthermore describe the
      rate of degradation of different vicilin subunits. The detected diversity and
      dynamics of vicilin peptides will help to define biochemical markers of distinct
      steps of the fermentation process.

PMID- 29195892
TI  - A consumer-based approach to salt reduction: Case study with bread.
AB  - In recent years high sodium intake has raised growing concern worldwide. A
      widespread reduction of salt concentration in processed foods has been claimed as
      one of the most effective strategies to achieve a short-term impact on global
      health. However, one of the major challenges in reducing salt in food products is
      its potential negative impact on consumer perception. For this reason, gradual
      salt reduction has been recommended. In this context, the aim of the present work
      was to present a consumer-based approach to salt reduction, using bread as case
      study. Two consumer studies with a total of 303 consumers were carried out. In
      the first study, four sequential difference thresholds were determined through
      paired-comparison tests, starting at a salt concentration of 2%. In the second
      study, 99 consumers performed a two-bite evaluation of their sensory and hedonic
      perception of five bread samples: a control bread containing 2% salt and four
      samples with reduced salt content according to the difference thresholds
      determined in the first study. Survival analysis was used to determine average
      difference thresholds, which ranged from 9.4% to 14.3% of the salt concentration
      of the control bread. Results showed that salt concentration significantly
      influenced consumer overall liking of the bread samples. However, large
      heterogeneity was found in consumer hedonic reaction towards salt reduction: two
      groups of consumers with different preference and hedonic sensitivity to salt
      reduction were found. Results from the present work confirm that cumulative
      series of small salt reductions may be a feasible strategy for reducing the
      sodium content of bread without affecting consumer hedonic perception and stress
      the importance of considering consumer perception in the design of gradual salt
      reduction programmes.

PMID- 29195893
TI  - Application of bacteriophages during depuration reduces the load of Salmonella
      Typhimurium in cockles.
AB  - As bivalve molluscs are filter feeder, often consumed raw or lightly cooked and
      are frequently cultivated in contaminated waters, they are implicated in food
      borne disease transmission to human. The present study investigated the potential
      application of bacteriophage (or phage) phSE-2, phage phSE-5 and phage cocktail
      phSE-2/phSE-5 to decrease the concentration of Salmonella enterica serovar
      Typhimurium (Salmonella Typhimurium) during the depuration of natural and
      artificially contaminated cockles (Cerastoderma edule). Cockles were artificially
      infected with 105 and 106colony-forming units (CFU)/mL of S. Typhimurium in
      static seawater and infected group were treated with phages at four different MOI
      values: 0.1, 1, 10 and 100. Depuration in static seawater at multiplicity of
      infection (MOI) of 0.1 with single phage suspensions of phSE-2 and phSE-5
      provided the best results, as it decreased by ~1.3 and 1.7 logCFU/g,
      respectively, the concentration of Salmonella spp. after a 4h treatment. At a MOI
      of 0.1, the rate of inactivation with single phage suspensions was higher when
      compared with the results obtained using the phage cocktail. However, in
      naturally contaminated cockles treated in static seawater with single phage
      suspensions and phage cocktail phSE-2/phSE-5, similar decreases in cultivable
      bacteria concentration (~0.7-0.9 logCFU/g) were achieved after 6h of treatment.
      When artificially contaminated cockles were depurated with phage phSE-5 in a
      recirculated seawater system (mimicking industrial depuration conditions), a 0.9
      and 2.0 logCFU/g reduction of Salmonella spp. was reached after 4 and 6h
      treatment. Once the depuration process was performed without phage, a 6h
      treatment was needed to obtain a 1.1 logCFU/g reduction of Salmonella spp.
      Results indicated that combining phage biocontrol with depuration procedures
      enhance bivalve microbial safety for human consumption by improving
      decontamination efficiency, proving that this technology can be transposed to the
      bivalves industry. Moreover, this approach also displays the advantage of
      reducing the time required for depuration and consequently its associated costs.

PMID- 29195894
TI  - Protective role of glutathione addition against wine-related stress in Oenococcus
      oeni.
AB  - Oenococcus oeni is the main species responsible for the malolactic fermentation
      (MLF) of wine due to its ability to survive in this environment. Some wine
      related stress factors, such as ethanol and low pH, may alter the cell redox
      balance of O. oeni. For the first time, the ability to uptake glutathione (GSH),
      an almost universal tripeptide with antioxidant properties, has been associated
      to the improvement of stress response in O. oeni. Despite the inability of O.
      oeni to synthesize GSH, this bacterium can capture it from the media. The ability
      of 30 O. oeni strains to uptake GSH was assessed in this study. Although all of
      the strains tested were able to import GSH, substantial variability among them
      was detected. To assess the physiological function of GSH, three strains with
      different GSH-import capacities were selected. Significant changes in membrane
      fatty acids composition were observed due to GSH addition. The most relevant was
      the increase of cyclopropane fatty acids in cell membrane, in both the
      exponential and the stationary phases. Cells grown with GSH showed an improved
      survival against ethanol shock (14% v/v). GSH addition also increased biomass
      production during the adaptation to wine stress conditions (pH4, pH3.4 and 6%
      ethanol). The results suggest that GSH enrichment could improve the resistance to
      stress to O. oeni, which could be useful for the adaptation of MLF starter
      cultures.

PMID- 29195895
TI  - Structural and rheological properties of xanthan gum/lysozyme system induced by
      in situ acidification.
AB  - Structural and rheological properties of xanthan gum/lysozyme (XG/Ly) system
      induced by electrostatic interaction through in situ acidification were
      investigated. The two biopolymers transited from co-solubility state to form
      soluble complexes, and finally produced tenuous network as the pH further
      decreased. The fluorescent images indicated that the network was cross-linked of
      XG chains by Ly, liking a polymerization process which resulted in the sol-gel
      transition by electrostatic interactions. High Ly content could accelerate the
      phase transition at the same pH condition, while XG played a contrary role. XG
      addition could enhance the thermal stability of Ly. The phase transition was also
      illustrated by zeta-potential at different pHs. The boundary parameters were
      determined to distinguish the phase transition regions. At the pH higher than
      pHphi, the negatively liked XG and Ly were in co-soluble state. They formed
      soluble complexes at the pH between pHphi and pHg, and gel was obtained with net
      microstructure as the pH continuously decreased (lower than pHg). The paper
      provides practical parameters that may be applicable in controlling the
      structure, texture, and stability of polysaccharide/protein system, as well as in
      food and medicinal application with various purposes.

PMID- 29195896
TI  - An itinerant sensory approach to investigate consumers' perception and
      acceptability at a food exhibition.
AB  - In a food exhibition where several producers of the same product category are
      present at the same time, consumers usually have the opportunity to taste several
      free samples of the same product type, thus they can experience and compare the
      sensory characteristics of each and evaluate their liking for each sample tasted.
      This study assessed the potential of an itinerant sensory data collection in
      understanding the consumers' perception and acceptance of cheese during a
      multiple tasting experience at a food exhibition. Subjects tasted seven samples
      of Parmigiano Reggiano cheese aged for different times (24 and 36months) at seven
      producer stands and recorded their evaluations using tablets, on which an
      application specifically developed for this study was installed. This evaluation
      situation was defined as "pseudo-natural," in opposition to the "natural" and the
      "naturalistic" settings. The itinerant sensory session comprised a liking test, a
      rate-all-that-apply (RATA) test using a just about right (JAR) scale, a food
      pairing test, and a questionnaire. Consumers significantly (p<0.05) discriminated
      the cheeses as a function of the aging time, describing with different attributes
      the 24months (sweetness, fresh fruit, grass, yogurt, butter flavors, elasticity,
      and humidity) and the 36months (saltiness, bitterness, sourness, spicy, aromatic
      herbs, cheese rind flavors, crumbliness, granularity, hardness, and hotness) aged
      products. The combined application of regression models, Penalty-Lift analysis,
      and decision tree models in investigating the relationships between liking and
      the RATA data, provided results revealing that the attributes elasticity,
      sweetness, humidity, fresh fruit, and butter were the main drivers of liking.
      Whereas, the attributes sourness, bitterness, and hardness were the main drivers
      of dislike. Therefore, even though no significant differences in terms of liking
      were observed among the tested cheeses, consumers preferred the attributes more
      frequently perceived in the least aged products. In conclusion, the presented
      itinerant sensory approach had provided meaningful information to understand the
      consumers' cheese perception and acceptability. In the future, it could
      advantageously be applied for studying food perception in other situations in
      which subjects naturally choose or consume several products while freely moving
      from one to another (e.g. self-service restaurant).

PMID- 29195897
TI  - An inflammatory environment containing TNFalpha favors Tet2-mutant clonal
      hematopoiesis.
AB  - Clonal hematopoiesis of aging and indeterminate potential (ARCH or CHIP), driven
      mainly by mutations in DNMT3A and TET2, is an emerging public health issue,
      affecting at least 10-15% of adults older than 65 years. CHIP is associated with
      increased risks of de novo and therapy-related hematological neoplasms and serves
      as a reservoir for leukemic relapse. CHIP is also associated with increased all
      cause mortality and risk of cardio-metabolic disease. The latter association may
      be explained, at least in part, by the effects of inactivating mutations in TET2
      on progeny macrophages. We and others have shown recently that TET2-deficient
      macrophages are hyperinflammatory and this may exacerbate processes such as
      atherosclerosis. We postulated an inflammatory state associated with TET2
      inactivation and/or unhealthy aging may also favor TET2-mutant hematopoietic stem
      and progenitor cell (HSPC) expansion. Herein, we demonstrate a clonogenic
      advantage for Tet2-knockout murine and TET2-mutant human HSPCs in an in vitro
      environment that contains the proinflammatory cytokine tumor necrosis factor
      alpha (TNFalpha). This phenotype emerges on chronic TNFalpha exposure and is
      associated with myeloid skewing and resistance to apoptosis. To our knowledge,
      this is the first evidence to suggest that TET2 mutations promote clonal
      dominance with aging by conferring TNFalpha resistance to sensitive bone marrow
      progenitors while also propagating such an inflammatory environment. Normalizing
      the immune environment may present a novel strategy to control or eradicate
      mutant CHIP clones.

PMID- 29195898
TI  - Outcomes of displaced olecranon fractures treated with the Olecranon Sled.
AB  - BACKGROUND: Tension-band wiring is largely considered the gold standard for
      fixation of displaced olecranon fractures despite high rates of hardware
      complications. The purpose of this study was to report the outcomes of displaced
      olecranon fractures treated with the Olecranon Sled. METHODS: We retrospectively
      reviewed all displaced olecranon fractures from 2011-2015 treated with the
      Olecranon Sled. Inclusion was limited to functionally independent patients with
      Mayo type II fractures and minimum 12-month follow-up. We assessed clinical
      outcomes including range of motion; Disabilities of the Arm, Shoulder and Hand
      score; and Mayo Elbow Performance Score. RESULTS: Twenty-two patients with a mean
      follow-up period of 31.8 months (range, 12-71 months) were included in the study.
      All patients indicated satisfactory outcomes. The mean Mayo Elbow Performance
      Score was 95.5 (range, 70-100), and the mean Disabilities of the Arm, Shoulder
      and Hand score was 3.1 (range, 0-18.3). The mean total arc of elbow flexion was
      145 degrees  (range, 134 degrees -158 degrees ), and the mean total arc of
      forearm rotation was 175 degrees  (range, 160 degrees -180 degrees ). There were
      no hardware-related complications. The overall complication rate was 4.5% (1 of
      22) as significant heterotopic ossification developed in 1 patient, requiring
      contracture release. CONCLUSION: The Olecranon Sled is a reliable and well
      tolerated implant for the treatment of olecranon fractures. This device results
      in excellent functional outcomes and may obviate hardware removal.

PMID- 29195899
TI  - Ibuprofen impairs capsulolabral healing in a rat model of anterior glenohumeral
      instability.
AB  - BACKGROUND: Failure of glenoid labrum and capsular healing after glenohumeral
      dislocation can lead to persistent shoulder instability. The purpose of this
      study was to determine the effect of nonsteroidal anti-inflammatory drugs
      (NSAIDs) on the healing glenoid labrum and capsule after glenohumeral dislocation
      in a rat model. METHODS: Sixty-six rats had surgically induced anterior-inferior
      labral tears and anterior glenohumeral dislocation. Postoperatively, the animals
      were assigned to either normal (n = 32) or ibuprofen drinking water (n = 31).
      Animals were euthanized at 2 and 4 weeks postoperatively for biomechanical
      testing and histologic analysis. RESULTS: The maximum load increased from 2 to 4
      weeks after injury in the NSAID groups but not in the control groups. At 2 weeks,
      the maximum load was lower in the NSAID group compared with the control group. In
      a matched comparison between injured and uninjured limbs, the maximum load was
      significantly decreased in the injured limb of the 2-week NSAID group. At 4
      weeks, the NSAID group had decreased stiffness compared with the 4-week control
      group. CONCLUSIONS: In a new rat model of glenohumeral instability, the
      postinjury administration of ibuprofen resulted in decreased capsulolabral
      healing. A matched pair analysis of injured to uninjured limbs supported the
      findings of impaired healing in the NSAID-treated animals. These findings
      demonstrate that the use of NSAIDs after glenohumeral dislocation may impair
      capsulolabral healing and should be limited or avoided to optimize glenohumeral
      stability.

PMID- 29195900
TI  - Outcomes for subscapularis management techniques in shoulder arthroplasty: a
      systematic review.
AB  - BACKGROUND: This systematic review aims to synthesize published data for the most
      common subscapularis takedown and repair to compare outcomes in the setting of
      shoulder arthroplasty. METHODS: Searches of MEDLINE and Cochrane Library
      databases identified studies that reported clinical or radiologic outcomes for
      subscapularis management in the setting of shoulder arthroplasty. Comparisons
      included musculotendinous integrity, subscapularis testing and strength, shoulder
      range of motion, and functional outcome scores. RESULTS: The 14 included studies
      reported considerable variability in techniques, outcomes, and musculotendinous
      integrity. Lesser tuberosity osteotomy (LTO) demonstrated better healing rates
      (93.1%) than subscapularis peel (SP; 84.1%) and midsubstance tenotomy (ST;
      75.7%), although not significantly different. A statistically significant
      increase in fatty infiltration was found after surgery across techniques, and
      range of motion and strength were similar. Mean rates of normal results for belly
      press and lift-off tests were uniformly better for LTO (79.1% and 80.7%) over ST
      (66.7% and 65.6%), although multiple studies showed poor correlation between
      subscapularis functional testing and musculotendinous integrity. Mean total
      Constant and Western Ontario Osteoarthritis of the Shoulder Index outcome scores
      were slightly better for LTO (77.6, 84.2) than for SP (71.8 and 82.7). Mean
      American Shoulder and Elbow Surgeons scores favored the ST group (80.8) over the
      SP (79.1) and LTO (73) groups. CONCLUSIONS: The data suggest no significant
      differences exist for postoperative musculotendinous integrity or clinical
      outcomes among the subscapularis management techniques in shoulder arthroplasty.
      Subscapularis healing and integrity appear to favor the lesser tuberosity
      takedown method. Additional randomized controlled comparisons with long-term
      follow-up are needed to more effectively compare these surgical approaches.

PMID- 29195901
TI  - Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by
      inhibiting TGFB1-dependent epithelial mesenchymal transition.
AB  - Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell
      proliferation that damages the body. This malignant cell evolution in a stressful
      environment closely resembles that of epithelial-mesenchymal transition (EMT). As
      a popular EMT-inducing factor, TGFbeta plays an important role in the progression
      of multiple diseases. However, the drugs that target TGFB1 are limited. In this
      study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti
      lung fibrosis effect by inhibiting the EMT of lung epithelial cells. In addition,
      triptolide directly binds to TGFbeta and subsequently increase E-cadherin
      expression and decrease vimentin expression. In in vivo studies, TPL improves the
      survival state and inhibits lung fibrosis in mice. In summary, this study
      revealed the potential therapeutic effect of paraquat induced TPL in lung
      fibrosis by regulating TGFbeta-dependent EMT progression.

PMID- 29195902
TI  - Indoxyl sulfate accelerates vascular smooth muscle cell calcification via
      microRNA-29b dependent regulation of Wnt/beta-catenin signaling.
AB  - Vascular calcification (VC) is a very common phenomenon in patients with chronic
      kidney disease(CKD) and it increases the incidence of cardiovascular disease and
      leads to high mortality in CKD patients. It has been reported that some microRNAs
      (miRs) play roles in vascular calcification as an epigenetic regulator. Indoxyl
      sulfate (IS) is a protein-bound uremic toxin which has been proven as one of the
      major risk factors of cardiovascular disease in CKD. Here we investigated whether
      microRNA-29b (miR-29b) is involved in IS-induced vascular calcification. We found
      that vascular miR-29b was down-regulated in radial arteries of patients with end
      stage renal disease. Consistently, IS also decreased miR-29b expression in human
      aortic smooth muscle cells (HASMCs) and potentiated their calcification. MiR-29b
      mimics significantly suppressed, while miR-29b anti-miR markedly enhanced, IS
      induced runt-related transcription factor 2 and osteopontin expression. The
      expression of Wnt7b/beta-catenin in radial arteries was higher in end stage renal
      disease than in control group, and IS increased Wnt7b/beta-catenin expression in
      HASMCs as early as 3days after stimulation. Furthermore, miR-29b mimics potently
      repressed Wnt7b/beta-catenin protein expression in HASMCs, whereas miR-29b anti
      miR increased their expression, indicating miR-29b indeed negatively regulates
      Wnt7b/beta-catenin signaling. Dickkopf-1 protein, the Wnt/beta-catenin signaling
      inhibitor, suppressed anti-miR-29b-enhanced HASMCs calcification. Our data thus
      indicate that miR-29b downregulation and Wnt/beta-catenin signaling activation
      may be the key mechanism of IS induced vascular calcification in chronic kidney
      disease.

PMID- 29195903
TI  - Reply to Foley et al., "Acute myeloid leukemia with t(14;21) involving RUNX1 and
      SYNE2: A novel favorable-risk translocation?"

PMID- 29195904
TI  - Worldwide burden of cancer attributable to diabetes and high body-mass index: a
      comparative risk assessment.
AB  - BACKGROUND: Diabetes and high body-mass index (BMI) are associated with increased
      risk of several cancers, and are increasing in prevalence in most countries. We
      estimated the cancer incidence attributable to diabetes and high BMI as
      individual risk factors and in combination, by country and sex. METHODS: We
      estimated population attributable fractions for 12 cancers by age and sex for 175
      countries in 2012. We defined high BMI as a BMI greater than or equal to 25
      kg/m2. We used comprehensive prevalence estimates of diabetes and BMI categories
      in 2002, assuming a 10-year lag between exposure to diabetes or high BMI and
      incidence of cancer, combined with relative risks from published estimates, to
      quantify contribution of diabetes and high BMI to site-specific cancers,
      individually and combined as independent risk factors and in a conservative
      scenario in which we assumed full overlap of risk of diabetes and high BMI. We
      then used GLOBOCAN cancer incidence data to estimate the number of cancer cases
      attributable to the two risk factors. We also estimated the number of cancer
      cases in 2012 that were attributable to increases in the prevalence of diabetes
      and high BMI from 1980 to 2002. All analyses were done at individual country
      level and grouped by region for reporting. FINDINGS: We estimated that 5.6% of
      all incident cancers in 2012 were attributable to the combined effects of
      diabetes and high BMI as independent risk factors, corresponding to 792 600 new
      cases. 187 600 (24.5%) of 766 000 cases of liver cancer and 121 700 (38.4%) of
      317 000 cases of endometrial cancer were attributable to these risk factors. In
      the conservative scenario, about 4.5% (626 900 new cases) of all incident cancers
      assessed were attributable to diabetes and high BMI combined. Individually, high
      BMI (544 300 cases) was responsible for twice as many cancer cases as diabetes
      (280 100 cases). 26.1% of diabetes-related cancers (equating to 77 000 new cases)
      and 31.9% of high BMI-related cancers (174 040 new cases) were attributable to
      increases in the prevalence of these risk factors from 1980 to 2002.
      INTERPRETATION: A substantial number of cancer cases are attributable to diabetes
      and high BMI. As the prevalence of these cancer risk factors increases, clinical
      and public health efforts should focus on identifying optimal preventive and
      screening measures for whole populations and individual patients. FUNDING: NIHR
      and Wellcome Trust.

PMID- 29195905
TI  - Diabetes and adiposity: a heavy load for cancer.

PMID- 29195906
TI  - Patterns and predictors of emergency department visits among older patients after
      breast cancer surgery: A population-based cohort study.
AB  - OBJECTIVES: To characterize rates, reasons for, and associated predictors for
      emergency department (ED) visits after breast cancer (BC) surgery. METHODS: All
      women over 65 years undergoing curative surgery for non-metastatic incident BC
      (1998-2012) were identified using Quebec's universal healthcare administrative
      databases. Reasons for ED visits within 45days of operation were reported.
      Associated factors were estimated using Cox regression. RESULTS: Of 24,463
      patients, 12.8% had postoperative ED visits. Most frequent reasons were:
      superficial infection, noninfectious gastrointestinal, trauma or wound (other
      than breast), noninfectious respiratory, and breast wound disruption. Significant
      predictors included localized (aHR, 1.24, CI 1.04-1.49) or regional disease (aHR
      1.64, CI 1.41-1.92), mastectomy (aHR 1.22, CI 1.10-1.34), each operation before
      definitive oncologic control (aHR 1.12, CI 1.03-1.21), lower institutional volume
      (aHR 1.23, CI 1.09-1.38), having 6-10 prescriptions (aHR 1.23, CI 1.15-1.31) or
      >10 (aHR 1.53, CI 1.33-1.77), benzodiazepine use (aHR 1.09, CI 1.01-1.18),
      anticoagulant use (aHR 1.29, CI 1.13-1.46), cardiovascular disease (aHR 1.15, CI
      1.05-1.26), diabetes (aHR 1.11, CI 1.00-1.24), past hospitalization (aHR 1.25, CI
      1.17-1.34), and lower income (aHR 1.12, CI 1.04-1.20). CONCLUSION: Identification
      of risk factors in older patients before BC surgery could help prevent
      postoperative ED visits.

PMID- 29195907
TI  - Presynaptic alpha2-adrenoceptor modulates glutamatergic synaptic transmission in
      rat nucleus accumbens in vitro.
AB  - The nucleus accumbens (NAc), integrating information from the prefrontal cortex
      and limbic structures, plays a critical role in reward and emotion regulation.
      Previous studies have reported that the NAc shell receives direct noradrenergic
      projections, and activation of alpha2-adrenoceptor (alpha2-AR) in the NAc shell
      decreases the fear or anxiety level of rats. However, the underlying mechanism is
      still little known. Intriguingly, glutamatergic neurotransmission in the NAc
      shell is closely related to reward and emotion. Here, using brain slice
      preparations and whole-cell patch clamp recordings, we examined the effect of
      activation of alpha2-AR on glutamatergic neurotransmission in the NAc shell.
      Perfusing slice with alpha2-AR selective agonist clonidine (CLON) reduced the
      evoked excitatory postsynaptic currents (EPSCs) on the NAc shell neurons. This
      inhibitory effect on AMPA-mediated glutamatergic EPSCs was blocked by the alpha2
      AR selective antagonist yohimbine (YOH). Notably, CLON reduced the frequency but
      not the amplitude of miniature EPSCs. Furthermore, CLON decreased the first EPSC
      amplitude but increased the paired-pulse facilitation on the NAc shell neurons,
      and it did not affect postsynaptic AMPA/NMDA ratio, revealing a presynaptic
      mechanism of alpha2-AR-mediated inhibition on glutamatergic transmission. In
      addition, the modulation on glutamatergic transmission by alpha2-AR was
      independent of presynaptic NMDA receptor. These results suggest that
      noradrenergic afferent inputs may suppress glutamatergic synaptic transmission
      via presynaptic alpha2-AR in the NAc shell, and actively participate in rewarding
      and emotional processes via the NAc.

PMID- 29195908
TI  - Analysis of long non-coding RNA expression profiles following focal cerebral
      ischemia in mice.
AB  - Long noncoding RNAs (lncRNAs) have a variety of biological functions and play key
      roles in many diseases. However, the knowledge of lncRNA function during a stroke
      is limited. We analyzed the expression profiles of lncRNAs in the brain ischemic
      region of mice after a 45min middle cerebral artery occlusion (MCAO) with a 48h
      reperfusion. Gene ontology and pathway analysis were used to elucidate the
      potential functions of the differentially expressed mRNAs. A total of 255 lncRNAs
      (217 up-regulated and 38 down-regulated) and 894 mRNAs (870 up-regulated and 24
      down-regulated) showed significantly altered expression in the ischemic brain
      compared to the sham controls (fold change ?>2, P?0.05). The gene ontology terms
      were mainly associated with neutrophil chemotaxis, positive regulation of
      inflammatory response, cell cycle, positive regulation of apoptotic process, and
      apoptotic process. The pathway analysis indicated that the mRNAs were mainly
      associated with inflammatory pathways. Additionally, the interactions between the
      differentially expressed lncRNAs and mRNAs are revealed by a dynamic lncRNA-mRNA
      network. Our findings provide an overview of aberrantly expressed lncRNAs in
      stroke and further broaden the understanding of stroke pathogenesis.

PMID- 29195910
TI  - Dispelling myths about connexins, pannexins and P2X7 in hypoxic-ischemic central
      nervous system.
AB  - In membrane physiology, as in other fields, myths or speculations may be repeated
      so often and so widely that they are perceived as facts. To some extent, this has
      occurred with regard to gap junctions, hemichannels, pannexin channels and P2X7
      (ionotropic receptors), especially concerning the interpretation of the
      individual role of these channels in hypoxic-ischemic CNS since these channels
      may be closed by the same pharmacological blockers. Significance of existing
      controversial data are highlighted and contradictory views from different groups
      are critically discussed herein.

PMID- 29195909
TI  - Protective effects of gamma-mangostin on 6-OHDA-induced toxicity in SH-SY5Y
      cells.
AB  - gamma-Mangostin is a xanthone with hydroxyl groups that confer the substance-free
      radical scavenging effects. As opposed to the other more extensively studied
      mangostins, scarce research has been conducted on neuroprotective effects of
      gamma-mangostin on models of Parkinson's disease (PD). Therefore, this
      investigation aimed to elucidate its antioxidant and neuroprotective effects on 6
      OHDA-induced toxicity in SH-SY5Y cells. 6-OHDA treatment, an inducer of PD
      pathology in vitro studies, decreased cell viability and increased the level of
      intracellular ROS production. Furthermore, the substance-induced the expression
      of phosphorylated p38 MAPK, negatively affected the Bax/Bcl-2 ratio and increased
      caspase-3 activity; all of which were factors that are associated with apoptosis.
      Pretreatment of cells with gamma-mangostin at concentrations of 0.5, 1, and
      2.5MUM markedly increased cell survival and reduced the level of intracellular
      ROS formation as shown by DPPH radical scavenging activity of the compound.
      Furthermore, a significant suppression of p-p38, improved Bax/Bcl-2 ratio
      expression, and reduced caspase-3 activity was exhibited in the cells after gamma
      mangostin pretreatment. The reduction of apoptosis was further supported by the
      reduction of pyknotic nuclei indicated by Hoescht 33342 staining. These findings
      indicate that gamma-mangostin could attenuate 6-OHDA-induced neuronal cell death
      and that the protective effect of gamma-mangostin is associated with its
      antioxidative potential and through the modulation of the apoptotic signalling
      pathway. Therefore, gamma-mangostin may be an effective xanthone among other
      mangostins for preventing neurodegeneration in PD caused by oxidative stress.

PMID- 29195912
TI  - Procedure-Specific Trends in Surgical Outcomes.
AB  - BACKGROUND: Quality improvement efforts have generally focused on hospital
      benchmarking, and processes and outcomes shared among all operations. However,
      quality improvement could be inconsistent across different types of operations.
      The objective of this study was to identify operations needing additional
      concerted quality improvement efforts by examining their outcomes trends. STUDY
      DESIGN: Ten procedures (colectomy, esophagectomy, hepatectomy, hysterectomy,
      pancreatectomy, proctectomy, total hip arthroplasty, total knee arthroplasty,
      thyroidectomy, and ventral hernia repair) commonly accrued into the American
      College of Surgeons NSQIP between 2008 and 2015 were included. Trends in risk
      adjusted, standardized, smoothed rates were constructed for each procedure across
      6 outcomes (mortality, pneumonia, renal failure, surgical site infection,
      unplanned intubation, and urinary tract infection [UTI]). RESULTS: Of 1,255,575
      operations analyzed, the overall unadjusted rate for mortality across all 10
      procedures was 1.08%, for pneumonia 1.44%, for renal failure 0.67%, for surgical
      site infection 5.28%, for unplanned intubation 1.11%, and for UTI 1.86%.
      Hepatectomy demonstrated the greatest improvement across outcomes (4 of 6
      outcomes; 362 adverse events avoided out of 10,000 procedures), and UTI
      demonstrated the greatest improvement across procedures (8 of 10 procedures; 989
      adverse events avoided out of 10,000). For pancreatectomy, rates of mortality,
      unplanned intubation, and UTI improved, but surgical site infection rates were
      detected to have significantly increased (p < 0.05). CONCLUSIONS: Hepatectomy was
      detected to have improved across the greatest number of outcomes, and UTI rates
      improved significantly across the greatest number of procedures. Surgical site
      infection rates after pancreatectomy, however, were detected to have increased,
      identifying an urgent need for additional concerted quality improvement efforts.

PMID- 29195913
TI  - Association of office and ambulatory blood pressure with blood lead in workers
      before occupational exposure.
AB  - In view of decreasing lead exposure and guidelines endorsing ambulatory above
      office blood pressure (BP) measurement, we reassessed association of BP with
      blood lead (BL) in 236 newly employed men (mean age, 28.6 years) without previous
      lead exposure not treated for hypertension. Office BP was the mean of five
      auscultatory readings at one visit. Twenty-four-hour BP was recorded at 15- and
      30-minute intervals during wakefulness and sleep. BL was determined by
      inductively coupled plasma mass spectrometry. Systolic/diastolic office BP
      averaged 120.0/80.7 mm Hg, and the 24-hour, awake, and asleep BP 125.5/73.6,
      129.3/77.9, and 117.6/65.0 mm Hg, respectively. The geometric mean of blood lead
      was 4.5 MUg/dL (interquartile range, 2.60-9.15 MUg/dL). In multivariable-adjusted
      analyses, effect sizes associated with BL doubling were 0.79/0.87 mm Hg (P =
      .11/.043) for office BP and 0.29/-0.25, 0.60/-0.10, and -0.40/-0.43 mm Hg for 24
      hour, awake, and asleep BP (P >= .33). Neither office nor 24-hour ambulatory
      hypertension was related to BL (P >= .14). A clinically relevant white coat
      effect (WCE; office minus awake BP, >=20/>=10 mm Hg) was attributable to
      exceeding the systolic or diastolic threshold in 1 and 45 workers, respectively.
      With BL doubling, the systolic/diastolic WCE increased by 0.20/0.97 mm Hg (P =
      .57/.046). Accounting for the presence of a diastolic WCE, reduced the
      association size of office diastolic BP with BL to 0.39 mm Hg (95% confidence
      interval, -0.20 to 1.33; P = .15). In conclusion, a cross-sectional analysis of
      newly hired workers before lead exposure identified the WCE as confounder of the
      association between office BP and BL and did not reveal any association between
      ambulatory BP and BL.

PMID- 29195911
TI  - The central extended amygdala in fear and anxiety: Closing the gap between
      mechanistic and neuroimaging research.
AB  - Anxiety disorders impose a staggering burden on public health, underscoring the
      need to develop a deeper understanding of the distributed neural circuits
      underlying extreme fear and anxiety. Recent work highlights the importance of the
      central extended amygdala, including the central nucleus of the amygdala (Ce) and
      neighboring bed nucleus of the stria terminalis (BST). Anatomical data indicate
      that the Ce and BST form a tightly interconnected unit, where different kinds of
      threat-relevant information can be integrated to assemble states of fear and
      anxiety. Neuroimaging studies show that the Ce and BST are engaged by a broad
      spectrum of potentially threat-relevant cues. Mechanistic work demonstrates that
      the Ce and BST are critically involved in organizing defensive responses to a
      wide range of threats. Studies in rodents have begun to reveal the specific
      molecules, cells, and microcircuits within the central extended amygdala that
      underlie signs of fear and anxiety, but the relevance of these tantalizing
      discoveries to human experience and disease remains unclear. Using a combination
      of focal perturbations and whole-brain imaging, a new generation of nonhuman
      primate studies is beginning to close this gap. This work opens the door to
      discovering the mechanisms underlying neuroimaging measures linked to
      pathological fear and anxiety, to understanding how the Ce and BST interact with
      one another and with distal brain regions to govern defensive responses to
      threat, and to developing improved intervention strategies.

PMID- 29195914
TI  - Early fluid loading for septic patients: Any safety limit needed?
AB  - Early adequate fluid loading was the corner stone of hemodynamic optimization for
      sepsis and septic shock. Meanwhile, recent recommended protocol for fluid
      resuscitation was increasingly debated on hemodynamic stability vs risk of
      overloading. In recent publications, it was found that a priority was often given
      to hemodynamic stability rather than organ function alternation in the early
      fluid resuscitation of sepsis. However, no safety limits were used at all in most
      of these reports. In this article, the rationality and safety of early aggressive
      fluid loading for septic patients were discussed. It was concluded that early
      aggressive fluid loading improved hemodynamics transitorily, but was probably
      traded off with a follow-up organ function impairment, such as worsening
      oxygenation by reduction of lung aeration, in a part of septic patients at least.
      Thus, a safeguard is needed against unnecessary excessive fluids in early
      aggressive fluid loading for septic patients.

PMID- 29195915
TI  - Development and in-vitro characterization of nanoemulsions loaded with
      paclitaxel/gamma-tocotrienol lipid conjugates.
AB  - Vitamin E TPGS is a tocopherol (alpha-T) based nonionic surfactant that was used
      in the formulation of the TocosolTM paclitaxel nanoemulsion, which was withdrawn
      from phase III clinical trials. Unlike tocopherols, however, the tocotrienol (T3)
      isomers of vitamin E were found to have innate anticancer activity and were shown
      to potentiate the antitumor activity of paclitaxel. The primary objective of the
      present study was therefore to develop a paclitaxel nanoemulsions by substituting
      alpha-T oil core of TocosolTM with gamma-T3 in, and vitamin E TPGS with PEGylated
      gamma-T3 as the shell, and test the nanoemulsions against Bx-PC-3 and PANC-1
      pancreatic tumor cells. A secondary objective was to test the activity of
      paclitaxel when directly conjugated with the gamma-T3 isomer of vitamin E. The
      synthesis of the conjugates was confirmed by NMR and mass spectroscopy. Developed
      nanoemulsions were loaded with free or lipid conjugated paclitaxel. Nanoemulsions
      droplets were <300 nm with fastest release observed with formulations loaded with
      free paclitaxel when gamma-T3 was used as the core. Substituting alpha-T with
      gamma-T3 was also found to potentiate the anticancer activity of the
      nanoemulsions. Although marginal increase in activity was observed when
      nanoemulsions were loaded with free paclitaxel, a significant increase in
      activity was observed when lipid conjugates were used. The results from this
      study suggest that the developed paclitaxel nanoemulsions with either gamma-T3,
      PEGylated gamma-T3, or paclitaxel lipid conjugates may represent a more promising
      option for paclitaxel delivery in cancer chemotherapy.

PMID- 29195916
TI  - Novel sulforaphane-enabled self-microemulsifying delivery systems (SFN-SMEDDS) of
      taxanes: Formulation development and in vitro cytotoxicity against breast cancer
      cells.
AB  - Paclitaxel (PTX) and docetaxel (DTX) are highly effective chemotherapeutic agents
      against breast cancer cells. Existing PTX and DTX formulations, however, contain
      excipients that result in a multitude of side-effects. The objective of the
      present study was to develop novel self-microemulsifying formulations of PTX and
      DTX with significantly lower excipient content by utilizing the high solubility
      of taxanes in sulforaphane (SFN). SFN-enabled microemulsions were developed by a
      screening process in which optical microscopy and absorbance data were used to
      monitor the physical stability of the dispersions. Optimized formulations
      contained vitamin E TPGS and transcutol to aid in taxane dissolution in water and
      the formation of transparent microemulsions (< 20 nm). SFN microemulsions were
      stable in different dilution media and storage temperatures and had no hemolytic
      effect on RBCs. When tested in vitro against MDA-MB-231 and MCF7 cancer cells by
      IncuCyte(r) live cell analysis and CellTiter-Blue(r) assay, taxanes/SFN
      microemulsions showed similar activity as the commercial taxanes injection
      solutions. SFN was only found to potentiate the activity of taxanes when used at
      high concentrations. This study highlighted the unique properties of SFN and its
      potential use in reformulating taxanes with high drug load and significantly
      lower excipient content than the commercial products.

PMID- 29195917
TI  - Conductive vancomycin-loaded mesoporous silica polypyrrole-based scaffolds for
      bone regeneration.
AB  - Bone tissue engineering is considered an alternative approach for conventional
      strategies available to treat bone defects. In this study, we have developed bone
      scaffolds composed of hydroxyapaptite (HAp), gelatin and mesoporous silica, all
      recognized as promising materials in bone tissue engineering due to favorable
      biocompatibility, osteoconductivity and drug delivery potential, respectively.
      These materials were coupled with conductive polypyrrole (PPy) polymer to create
      a novel bone scaffold for regenerative medicine. Conductive and non-conductive
      scaffolds were made by slurry casting method and loaded with a model antibiotic,
      vancomycin (VCM). Their properties were compared in different experiments in
      which scaffolds containing PPy showed good mechanical properties, higher protein
      adsorption and higher percentage of VCM release over a long duration of time
      compared to non-conductive scaffolds. Osteoblast cells were perfectly immersed
      into the gelatin matrix and remained viable for 14 days. Overall, new conductive
      composite bone scaffolds were created and the obtained results strongly verified
      the applicability of this conductive scaffold in drug delivery, encouraging its
      further development in tissue engineering applications.

PMID- 29195918
TI  - Characterization and in vivo efficacy of a heptapeptide ODT formulation for the
      treatment of neurogenic bladder dysfunction.
AB  - The objective of this study was to develop oral disintegrating tablet (ODT)
      formulations of a heptapeptide, [Lys5,MeLeu9,Nle10]-NKA(4-10), for the treatment
      of neurogenic bladder dysfunction. A design of experiment approach was applied to
      determine the optimal ratio of chosen excipients: gelatin (X1), glycine (X2), and
      sorbitol (X3). These formulations were optimized for efficacy studies to produce
      ODTs exhibiting rapid disintegration times (Y1) and appropriate structural
      integrity (Y2) using JMP(r) 12.0.1 software. Based on theoretically predicted
      values from 12 experimental runs, the optimal ODT formulation was determined to
      be 3% (w/v) gelatin, 2% (w/v) glycine, and 1% (w/v) sorbitol in deionized water.
      Using this formulation, blank and drug-loaded ODTs containing 1.5 mg or 5 mg of
      [Lys5,MeLeu9,Nle10]-NKA(4-10) were manufactured by a lyophilization process. The
      peptide-loaded tablets disintegrated in less than 30 s and released 97% of the
      peptide within 15 min. The peptide was stable for 90 days under 25  degrees C/60%
      relative humidity (RH) and 40  degrees C/75% RH. In vivo efficacy of the peptide
      loaded ODTs was confirmed in a rat acute spinal cord injury model under
      isovolumetric bladder pressure recording conditions, concluding that sublingual
      administration of peptide-containing ODTs evoke a rapid dose-related neurokinin 2
      mediated increase in bladder pressure.

PMID- 29195920
TI  - Loss of Lypd6 leads to reduced anxiety-like behaviour and enhanced responses to
      nicotine.
AB  - Nicotine consumption through smoking affects anxious states in humans. However,
      the precise role of nicotinic acetylcholine receptor (nAChR) circuitry in the
      regulation of anxiety remains elusive. The Lynx protein Lypd6 is highly enriched
      in synaptic loci and has been previously identified as an endogenous inhibitor of
      neuronal nAChR function in vitro. Here, we investigate the effect of Lypd6 in
      anxiety-related behaviour and examine the molecular underpinnings of its function
      in the brain. We employ the marble burying (MB) and elevated zero maze (EZM)
      tests in Lypd6 knock-out (KO) and wild-type (WT) mice and find that loss of Lypd6
      leads to decreased digging behaviour in the MB test and increased time spent in
      the open area in the EZM test. Moreover, we demonstrate that acute nicotine
      administration reduces digging in the MB test in both KO and WT mice and further
      accentuates the inherent genotype difference. Using in vitro electrophysiology in
      dorsal raphe nuclei (DRN) neurons from Lypd6 KO mice, we show that nicotine
      evoked whole-cell currents are enhanced in the absence of Lypd6. Collectively,
      these data are the first to indicate the involvement of Lypd6 in circuits
      associated with anxiety and suggest that a possible underlying neurobiological
      mechanism is the modulation of cholinergic responses in the DRN.

PMID- 29195919
TI  - S-Glutathionylation of p47phox sustains superoxide generation in activated
      neutrophils.
AB  - Post-translational modifications (PTMs) induced conformational changes of
      proteins can cause their activation or inactivation. Neutrophils clear pathogen
      through phagocytosis and oxidative burst generation, while participate in
      inflammation through sustained and uncontrolled generation of ROS. In activated
      PMNs, cytosolic NOX-2 subunit p47phox following phosphorylation interacts with
      p67phox, p40phox and along with Rac2 translocate to the membrane. Phosphorylation
      of p47phox subunit occurs in both short spurts as well as sustained ROS
      generation, suggesting towards the unidentified molecular mechanism(s) driving
      these two diverse outcomes by various stimuli. The present study demonstrates
      that in PMA or NO treated neutrophils a subunit of NOX2, p47phox gets
      glutathionylated to sustain ROS generation along with a decrease in catalase, Grx
      1 activity and change in GSH/GSSG ratio. Surprisingly, fMLP treated cells neither
      showed sustained ROS production nor glutathionylation of p47phox. S
      Glutathionylation was always secondary to phosphorylation of p47phox and
      inhibition of glutathionylation did not alter phosphorylation but specifically
      impaired sustained ROS production. Interestingly, forced S-glutathionylation of
      p47phox converted the fMLP induced ROS generation into sustained release of ROS.
      We then identified the glutathionylation susceptible cysteine residues of p47phox
      by LC-MS/MS with IAM switch mapping. Site-directed mutagenesis of cysteine
      residues further mitigated p47phox S-glutathionylation. Thus, we demonstrate that
      p47phox S-glutathionylation plays an essential key role in the sustained ROS
      generation by human neutrophils.

PMID- 29195921
TI  - Social cognition and self-other distinctions in neuropsychiatry: Insights from
      schizophrenia and Tourette syndrome.
AB  - Impairments in social cognition may reflect dysfunction of disorder specific or
      disorder general mechanisms. Although cross-disorder comparison may prove
      insightful, few studies have compared social cognition in different
      neuropsychiatric disorders. Parallel investigation of schizophrenia and Tourette
      syndrome (TS) is encouraged by similarities including the presence of problematic
      social behavior, echophenomena, emotional dysregulation and dopamine dysfunction.
      Focusing on tests of social cognition administered in both disorders, this review
      aims to summarize behavioral, neurophysiological and neuroimaging findings,
      before exploring how these may contribute to clinical symptoms. Studies
      investigating social cognition (imitation, emotion recognition, and understanding
      of beliefs or intentions) in patients with schizophrenia or TS were identified
      through Web of Science and PubMed searches. Although findings indicate that
      social cognitive deficits are more apparent in schizophrenia, adults with TS can
      exhibit similar task performance to patients with paranoia. In both disorders,
      behavioral and neuroimaging findings raise the possibility of increased internal
      simulation of others' actions and emotions, in combination with a relative under
      application of mentalizing. More specifically, dysfunction in neurobiological
      substrates such as temporo-parietal junction and inferior frontal gyrus may
      underlie problems with self-other distinctions in both schizophrenia and TS.
      Difficulties in distinguishing between actions and mental states linked to the
      self and other may contribute to a range of psychiatric symptoms, including
      emotional dysregulation, paranoia, social anhedonia and socially disruptive
      urges. Comparing different patient populations could therefore reveal common
      neuro-cognitive risk factors for the development of problematic social behaviors,
      in addition to markers of resilience, coping strategies and potential neuro
      compensation mechanisms.

PMID- 29195922
TI  - Association Between Cardiorespiratory Fitness and Health Care Costs: The Veterans
      Exercise Testing Study.
AB  - OBJECTIVE: To determine the association between cardiorespiratory fitness (CRF)
      and annual health care costs in Veterans. PATIENTS AND METHODS: The sample
      included 9942 subjects (mean age, 59+/-11 years) undergoing a maximal exercise
      test for clinical reasons between January 2005 and December 2012.
      Cardiorespiratory fitness, expressed as a percentage of age-predicted peak
      metabolic equivalents (METs) achieved, was categorized in quartiles. Total and
      annualized health care costs, derived from the Veterans Administration Allocated
      Resource Center, were compared using multiple regression, controlling for
      demographic and clinical characteristics. RESULTS: A gradient for reduced health
      care costs was observed as CRF increased, with subjects in the least-fit quartile
      having approximately $14,662 (P<.001) higher overall costs per patient per year
      compared with those in the fittest quartile, after controlling for potential
      confounding variables. Each 1-MET higher increment in fitness was associated with
      a $1592 annual reduction in health care costs (5.6% lower cost per MET), and each
      higher quartile of fitness was associated with a $4163 annual cost reduction per
      patient. The effect of CRF was more pronounced among subjects without
      cardiovascular disease (CVD), suggesting that the results were not driven by the
      possibility that less-fit individuals had greater CVD. Cost savings attributable
      to higher fitness were greatest in overweight and obese subjects, with lower
      savings observed among those individuals with a body mass index less than 25
      kg/m2. In a model including historical, clinical, and exercise test responses,
      heart failure was the strongest predictor of health care costs, followed by CRF
      (P<.01). CONCLUSION: Low CRF is associated with higher health care costs. Efforts
      to improve CRF may not only improve health but also result in lower health care
      costs.

PMID- 29195923
TI  - Calcific tendonitis of the rotator cuff: From formation to resorption.
AB  - Calcific tendonitis of the rotator cuff is due to apatite deposits in the
      shoulder tendons. Patients affected by calcific tendonitis have chronic shoulder
      pain and disability. Although the disease is frequent, about 10 to 42% of painful
      shoulders, mechanisms leading to this pathological mineralization are still
      largely unknown. Research reported in the 1990s suggested that the formation of
      calcific deposits is linked to cells looking like chondrocytes identified around
      calcium deposits within a fibrocartilage area. They were considered to be derived
      from tenocytes but more recently, tendon stem cells, able to differentiate into
      chondrocytes, were isolated. The pro-mineralizing properties of these
      chondrocytes-like cells, especially the role of alkaline phosphatase, are not
      currently clarified. The calcium deposits contain poorly crystalline carbonated
      apatite associated with protein. Among these proteins, only osteopontin has been
      consistently identified as a potential regulating factor. During the disease,
      spontaneous resorption can occur with migration of apatite crystals into the
      subacromial bursa causing severe pain and restriction of movement. In in vivo and
      in vitro experiments, apatite crystals were able to induce an influx of
      leucocytes and a release of IL-1beta and IL-18 through the activation of the
      NLRP3 inflammasome. However, mechanisms leading to spontaneous resolution of this
      inflammation and disappearance of the calcification still need to be elucidated.

PMID- 29195924
TI  - Adverse Reactions to Vaccination: From Anaphylaxis to Autoimmunity.
AB  - Vaccines are important for providing protection from infectious diseases.
      Vaccination initiates a process that stimulates development of a robust and long
      lived immune response to the disease agents in the vaccine. Side effects are
      sometimes associated with vaccination. These vary from development of acute
      hypersensitivity responses to vaccine components to local tissue reactions that
      are annoying but not significantly detrimental to the patient. The pathogenesis
      of these responses and the consequent clinical outcomes are discussed.
      Overstimulation of the immune response and the potential relationship to
      autoimmunity is evaluated in relation to genetic predisposition.

PMID- 29195925
TI  - Another Look at the "Dismal Science" and Jenner's Experiment.
AB  - The follow-up to Jenner's experiment, routine vaccination, has reduced more
      disease and saved more vertebrate lives than any other iatrogenic procedure by
      orders of magnitude. The unassailability of that potentially provocative cliche
      has been ciphered in human medicine, even if it is more difficult in our
      profession. Most public relations headaches concerning vaccines are a failure to
      communicate, often resulting in overly great expectations. Even in the throes of
      a tight appointment schedule remembering and synopsizing (for clients), some
      details of the dismal science can make practice great again.

PMID- 29195927
TI  - Effect of fish gelatin-gum arabic interactions on structural and functional
      properties of concentrated emulsions.
AB  - Concentrated emulsions containing both proteins and polysaccharides are the basis
      for many commercial products; however, the effects of protein-polysaccharide
      interactions on the functional properties of these complex systems are often
      poorly understood from a fundamental standpoint. Hence, the objective of this
      study was to determine the effects of fish gelatin (FG)-gum arabic (GA)
      complexation at different aqueous phase pH (3.6, 5.0, and 9.0) on concentrated
      emulsion structure-function relationships. Concentrated emulsions were prepared
      using FG-GA mixtures and characterized by rheometry and confocal scanning laser
      microscopy (CSLM). CSLM images showed that all samples were O/W emulsions;
      emulsions with lower pH showed smaller oil droplets, greater homogeneity in size
      distribution, and higher stability. This was attributed to an increased number of
      FG-GA complexes in the emulsification. Electrostatic attractive interactions and
      charge neutralization created biopolymer associations with increased
      emulsification capacity. Samples with FG-GA mixtures at lower pH showed higher
      elastic moduli under small deformation and exhibited greater deviation between
      apparent and complex viscosities under the Cox-Merz rule, indicating increased
      gel network extension and greater intermolecular connectivity between adsorbed
      layers of adjacent oil droplets. These results can be used to incorporate protein
      polysaccharide complexes as a suitable emulsifier in materials comprising
      concentrated emulsions.

PMID- 29195926
TI  - Clinicopathologic characteristics associated with long-term survival in advanced
      epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary
      data study.
AB  - OBJECTIVE: To identify clinicopathologic factors associated with 10-year overall
      survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC),
      and to develop a predictive model identifying long-term survivors. METHODS:
      Demographic, surgical, and clinicopathologic data were abstracted from GOG 182
      records. The association between clinical variables and long-term survival (LTS)
      (>10years) was assessed using multivariable regression analysis. Bootstrap
      methods were used to develop predictive models from known prognostic clinical
      factors and predictive accuracy was quantified using optimism-adjusted area under
      the receiver operating characteristic curve (AUC). RESULTS: The analysis dataset
      included 3010 evaluable patients, of whom 195 survived greater than ten years.
      These patients were more likely to have better performance status, endometrioid
      histology, stage III (rather than stage IV) disease, absence of ascites, less
      extensive preoperative disease distribution, microscopic disease residual
      following cyoreduction (R0), and decreased complexity of surgery (p<0.01).
      Multivariable regression analysis revealed that lower CA-125 levels, absence of
      ascites, stage, and R0 were significant independent predictors of LTS. A
      predictive model created using these variables had an AUC=0.729, which
      outperformed any of the individual predictors. CONCLUSIONS: The absence of
      ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors
      associated with LTS when controlling for other confounders. An extensively
      annotated clinicopathologic prediction model for LTS fell short of clinical
      utility suggesting that prognostic molecular profiles are needed to better
      predict which patients are likely to be long-term survivors.

PMID- 29195928
TI  - Acoustic cavitation assisted extraction of pectin from waste grapefruit peels: A
      green two-stage approach and its general mechanism.
AB  - In the present study, acoustic cavitation assisted extraction (ACAE) which is a
      green approach was used for two-stage extraction of pectin from waste grapefruit
      peels regarding the specific two stages and different peel particle sizes. The
      yields, physicochemical properties and structure prediction of pectin from
      different peel particle sizes and different stages by two methods were compared.
      Highest pectin yield of 23.49% was achieved at the peel size of 0.9mm and was
      slightly higher than the yield of 23.44% at finer particle size. ACAE achieved
      four times higher yield compared with conventional heating method (CHE) at the
      second stage. ACAE pectin which had lower molecular weight and degree of
      methoxylation was richer in rhamnogalacturonan-I (RG-I) region with long side
      chains compared with CHE pectin from chemical and FT-IR analysis. Based on the
      results, a potential general mechanism for ACAE of plant cell wall viscous
      polysaccharides was discussed in terms of the effects of cavitation on the
      swelling index and morphological study of residue to reveal the "barrier effect"
      during the process. Furthermore, the energy consumption for ACAE was
      significantly lower than the conventional method, indicating its promising
      application in industrial scale.

PMID- 29195929
TI  - Foam-stabilizing properties of the yeast protein PAU5 and evaluation of factors
      that can influence its concentration in must and wine.
AB  - The absence of the yeast protein seripauperin 5 (PAU5) from Saccharomyces
      cerevisiae has been suggested as a biomarker for the occurrence of gushing in
      sparkling wine as samples lacking PAU5 were found to be more susceptible to
      gushing. In this study, further characterization of PAU5 regarding its foam
      stabilizing properties was performed to elucidate whether PAU5 has foam
      stabilizing properties and therefore, to elucidate a direct influence on the
      gushing potential of sparkling wines. PAU5 was successfully purified from non
      gushing sparkling wine using reversed-phase high-performance liquid
      chromatography (RP-HPLC). Pure protein was added to grape juice as a model system
      for grape must prior to foam stability testing. The results revealed that the
      protein PAU5 has foam-stabilizing properties. Furthermore, the influence of heat
      and sulfur treatment in the presence of Botrytis cinerea was analyzed with regard
      to the amount of PAU5 produced by S. cerevisiae fermented in grape juice.
      Fermentation experiments using two different S. cerevisiae strains were
      performed, and the concentration of PAU5 in the samples was compared by RP-HPLC
      analysis. Unlike sulfur treatment, heat treatment prevented the protein
      degradation induced by B. cinerea and resulted in even higher amounts of PAU5
      compared to the juice fermented with yeast without a previous botrytization. The
      two different yeast strains applied secreted PAU5 into the surrounding medium in
      different amounts. In further experiments, the fining process of the wine with
      bentonite was examined for its potential to remove PAU5 from the wine. RP-HPLC of
      wines processed with different fining agents revealed that bentonite treatment
      affected PAU5 concentrations in the final product. The extent of PAU5 removal
      depended on the type of bentonite applied and on the time of addition during the
      production process.

PMID- 29195930
TI  - Chilean berry Ugni molinae Turcz. fruit and leaves extracts with interesting
      antioxidant, antimicrobial and tyrosinase inhibitory properties.
AB  - The knowledge of the biological properties of fruits and leaves of murta (Ugni
      molinae Turcz.) has been owned by native Chilean culture. The present study
      investigated the phenolic content, the antioxidant, antimicrobial and anti
      tyrosinase activities of different murta fruit and leaves extracts to approach
      their uses on future food, pharmaceutical and cosmetic applications. Extractions
      of murta fruit and leaves were carried out under water, ethanol and ethanol 50%.
      Phenolic content of these extracts was measured through Folin Ciocalteu test and
      the antioxidant power by four different antioxidant systems (ORAC, FRAP, DPPH and
      TEAC assays) owing to elucidate the main mechanism of antioxidant. Some
      flavonoids, such as rutin, isoquercitrin and quercitrin hydrate were identified
      and quantified through HPLC analysis. Antimicrobial activity was determined
      measuring minimum inhibition concentration (MIC) and minimum bactericidal
      concentration (MBC) values against Escherichia coli and Listeria monocytogenes,
      and the effect of these extracts on L. monocytogenes was confirmed by flow
      cytometry. Highest contents of polyphenol compounds were obtained in
      hydroalcoholic extracts (28+/-1mggallicacid/g dry fruit, and 128+/
      6mggallicacid/g dry leaves). The same trend was found for the values of
      biological properties: hydroalcoholic extracts showed the strongest activities.
      Leaves presented higher antioxidant, antimicrobial and anti-tyrosinase properties
      than murta fruit. Highest antioxidant activity values according to ORAC, FRAP,
      TEAC and DPPH were 80+/-8mgTrolox/g, 70+/-2mgTrolox/g, 87+/-8mgTrolox/g and 110+/
      12mgTrolox/g, respectively, for murta fruit samples, and 280+/-10mgTrolox/g,
      192+/-4mgTrolox/g, 286+/-13mgTrolox/g and 361+/-13mgTrolox/g, respectively, for
      murta leaves. These activities were confirmed by HPLC analysis that revealed
      highest presence of analyzed compounds on leaves hydroalcoholic extract.
      Regarding to antimicrobial analysis, hydroalcoholic leaves extract presented the
      highest activity presenting the lowest MIC value for L. monocytogenes
      (0.07mg/mL). This extract also performed the highest anti-tyrosinase activity
      (CE50 values of 1.6+/-0.3 (g/L) and 8.9+/-1.2 (g/L) for leaves and fruit,
      respectively).

PMID- 29195931
TI  - Effect of temperature in domestic refrigerators on fresh-cut Iceberg salad
      quality and waste.
AB  - The evolution of different quality parameters (firmness, weight loss, colour
      changes, microbial counts, consumer rejection) of packed fresh-cut Iceberg salad
      was assessed at 4, 8 and 12 degrees C to simulate domestic refrigerators running
      at different conditions. The increase in storage temperature did not affect salad
      firmness and weight loss but increased colour changes, microbial growth and
      consumer rejection. A survey among Italian consumers was also carried out and
      demonstrated that fresh-cut salad was mainly consumed within the first 5days
      after purchasing. Consumer rejection data were combined with data relevant to the
      distribution of salad consumption over the days following product purchase, to
      estimate salad wasting risk. When salad was stored at 4 and 8 degrees C,
      estimated wasted packages within the expiration date (7days) were <1%. By
      contrast, 13% of the packages was estimated to be wasted within 7days of storage
      at 12 degrees C. Quantification of wasting risk is a necessary information to
      identify efficient and sustainable interventions to tackle food waste.

PMID- 29195932
TI  - Effect of processing on phenolic acids composition and radical scavenging
      capacity of barley pasta.
AB  - Phenolic acids, total phenolics content and DPPH radical scavenging capacity in
      raw ingredients, fresh and dried spaghetti, and in uncooked and cooked spaghetti
      were evaluated and compared with semolina spaghetti as a reference. Ferulic acid
      was the major phenolic acid found in the free and bound phenolic extracts in all
      the investigated pasta samples. The addition of barley flour into pasta at
      incorporation levels of 30, 50 and 100% increased phenolic acids and total
      phenolics content. Pasta processing did not significantly affect the total
      phenolics content and free radical scavenging capacity, but a significant
      reduction in total phenolic acids measured by HPLC was found. Drying process
      differently affected individual phenolic compounds in the free and bound
      fractions, and thus, the total phenolic acids content. Free vanillic, caffeic and
      p-coumaric acids did not significantly change, while p-hydroxybenzoic and ferulic
      acids of the free extracts showed higher values compared to the corresponding
      fresh pasta. Cooking did not greatly affect total phenolic acids, more leading to
      conserving free and bound phenolic compounds.

PMID- 29195933
TI  - Effect of the molecular weight of a neutral polysaccharide on soy protein
      gelation.
AB  - The effects of galactomannans with different molecular weights on the heat
      induced gelation characteristics of soybean protein were investigated using
      dynamic small-strain rheometry, under conditions where the proteins carry a net
      negative charge (pH7). Microstructure of the resulting gels was investigated by
      confocal laser scanning microscopy. Phase-separated systems were obtained with
      different morphologies and degree of phase separation, depending on both
      biopolymer concentrations and polysaccharide molecular weight. In general, a
      gelling enhancing effect on soy proteins was verified, despite extensive phase
      separation processes observed at the higher polysaccharide molecular weight. This
      effect was demonstrated by an increase of the gelation rate, a decrease in the
      temperature at the onset of gelation, and an increase of gel stiffness and
      elastic character, with the length of polysaccharide chains. Overall, the results
      obtained established that the judicious selection of the galactomannan molecular
      weight may be used to modify the structure and gelation properties of soy
      proteins, originating a diversity of rheological characteristics and
      microstructures that will impact on the design of novel food formulations.

PMID- 29195934
TI  - Photocrosslinker technology: An antimicrobial efficacy of cinnamaldehyde cross
      linked low-density polyethylene (Cin-C-LDPE) as a novel food wrapper.
AB  - In recent years much attention has been devoted to active packaging technologies
      that offer new opportunities for the food industry and food preservation. The
      spoilage of food products during post process handling leads to food
      contamination and causes life-threatening food-borne illness. The methicillin
      resistant Staphylococcus aureus (MRSA) 090 is one of the food-borne pathogens
      associated with food poisoning that leads to an outbreak of perilous human
      infections worldwide. The development of resistance in bacteria and diffusion of
      coated synthetic preservatives into food are the major problem in food packaging
      industries. In the present work, we have developed a new food wrap method by
      cross-linking cinnamaldehyde on low-density polyethylene (Cin-C-LDPE) using novel
      photocrosslinker technology. The cinnamaldehyde showed potent antimicrobial
      activity (145mg/mL of MIC) against MRSA 090 and radical scavenging activity
      (RSA). The cinnamaldehyde was successfully cross-linked to LDPE and exhibited
      excellent antibiofilm properties against MRSA090 compared to bare LDPE. This
      positive interaction of developed Cin-C-LDPE against MRSA090 biofilm was
      confirmed by SEM and FT-IR studies, and results showed the damaged cell membrane
      architecture, inturn abridged adherence of MRSA090. The Cin-C-LDPE wrapped
      chicken, mutton, cheese, and grapes showed 2.5+/-0.15 log MRSA 090 reduction at
      the end of 10th day compared to the bare LDPE wrapped food samples. This clearly
      concludes that for the first time we have developed a novel Cin-C-LDPE food wrap
      technology effectively involved in biocidal activity against MRSA090. Applying
      this new strategy to develop food wrap containing nontoxic natural antimicrobial
      to target cell membrane components is the upcoming challenging and promising
      research gap remains in the food packaging industry for the future world.

PMID- 29195935
TI  - Effect of in vitro simulated gastrointestinal digestion on polyphenol and
      polysaccharide content and their biological activities among 22 fruit juices.
AB  - Polyphenols and polysaccharides, as natural bioactive compounds from common fresh
      fruits, are concerned in reducing risk of developing obesity and diabetes for
      human in recent years. The content of polyphenol and polysaccharide, their
      bioactivities among 22 fruit juices were investigated before and after in vitro
      gastrointestinal digestion in present study. After digestion, contents of
      polyphenol, polysaccharide and their antioxidant activity, the inhibitory
      activity of alpha-amylase and alpha-glucosidase significantly increased. Punica
      granatum Linn and Actinidia globosa C. F. Liang displayed maximal increment up to
      2, 0.25 and 1.6 fold in contents of polyphenols and polysaccharides, and the
      inhibitory activity of alpha-amylase, respectively. The correlation coefficient
      between contents and inhibitory activity of alpha-amylase increased in range of
      0.002 to 0.485. Lycopersicon esculentum Mill and Pyrus bretschneideri Rehd
      exhibited maximum increase in the inhibitory activity of alpha-glucosidase with
      lowest contents of polyphenols and polysaccharides. The results indicated that
      polyphenols and polysaccharides digested synergistically contributing to the
      inhibitory alpha-amylase activity, and other responsibly bioactive ingredients
      for inhibitory alpha-glucosidase activity would be worthy discussed future. The
      findings above highlighted some potential application of common fruit juices in
      controlling hyperglycemia and obesity.

PMID- 29195936
TI  - 1H NMR-based metabolomic fingerprinting to determine metabolite levels in serrano
      peppers (Capsicum annum L.) grown in two different regions.
AB  - Chili pepper (Capsicum annuum) is the most important and emblematic condiment in
      Mexican food. Serrano pepper is a variety of C. annuum that is traditionally
      cultivated in Mexico and commercialized in local markets. The aim of this study
      was to describe the 1H NMR metabolomic profiling of the aqueous phase of serrano
      peppers harvested from two distinct regions, in the states of Veracruz and
      Oaxaca, Mexico. According to the current results, aspartate citrate, lactate,
      leucine and sucrose were found at higher amount in the serrano peppers from
      Veracruz. On the other hand, acetate, formate, fumarate, malonate,
      phosphocholine, pyruvate and succinate showed the highest abundance in this
      product from Oaxaca. These are the main metabolites that distinguish one group
      from the other. The spectrometric method reported presently is characterized by
      great simplicity, robustness and reproducibility. Thus, this technique can be
      used for establishing reliable metabolomic fingerprints of serrano peppers grown
      under different environmental conditions.

PMID- 29195937
TI  - The French, German, and Spanish sound of eating fresh fruits and vegetables.
AB  - A set of onomatopoeic expressions for eating fruits and vegetables is compared
      across subjects whose native language is Spanish, French, or German. Subjects
      chose the onomatopoeia that best represented the sound of eating a fruit or
      vegetable (celery, banana, strawberry, passion fruit, mango, apple, orange, and
      tomato). Results show there are onomatopoeias that have a higher frequency of
      response in one language compared to the others. Thus, it is possible to assume
      that depending on the language there is a better way to express haptic and
      auditory information associated to fruit and vegetable consumption. Moreover, and
      considering the three languages, results show there are three categories of
      responses based on the relative strength of the material (strong and medium
      strength, and soft). Thus, there is some consistency in the onomatopoeias that
      represent the sound of eating a fruit or a vegetable. To conclude, results differ
      by language, but they are consistent within a category of sound.

PMID- 29195938
TI  - Technological aspects of horse meat products - A review.
AB  - Horse meat and its products can be considered as a food with a high nutritional
      value. However, due to cases of economically motivated food adulteration by the
      intentional addition of horse meat beef products in recent years, horse meat has
      become a controversial issue. Consumer confidence in meat products and the meat
      industry has diminished, although consumers consider the differences between the
      food content and the label as the major issue rather than the safety and
      nutritional characteristics of horse meat. The elaboration of meat products from
      horse meat (e.g. "cecina", dry-cured loin, salami, bressaola and pate) is also an
      interesting alternative to other traditional meat products such as dry-cured pork
      hams, pork sausages and liver pates. In this review, the technological aspects,
      safety and storage stability of meat products elaborated from horse meat will be
      addressed by highlighting the nutritional and sensory aspects of these meat
      products. We aim to improve the existing knowledge about horse meat in the view
      of recent scandals.

PMID- 29195939
TI  - Profiling and quantification of phenolic compounds in Camellia seed oils: Natural
      tea polyphenols in vegetable oil.
AB  - In Asia, tea seed oils (seed oils from Camellia oleifera, C. chekiangoleosa, and
      C. sinensis) are used in edible, medicinal, and cosmetic applications. However,
      these oils differ in their fatty acid contents, and there is little known about
      their phenolic compounds. Here we analyzed the phenolic compounds of seed oils
      from three species gathered from 15 regions of China. Twenty-four phenolic
      compounds were characterized by HPLC-Q-TOF-MS, including benzoic acids (6),
      cinnamic acids (6), a hydroxyphenylacetic acid, flavanols (4), flavonols (3),
      flavones (2), and dihydroflavonoids (2). Some of these phenolic compounds had not
      previously been reported from C. sinensis (20), C. oleifera (15), and C.
      chekiangoleosa (24) seed oils. Quantification was done by HPLC-QqQ-MS using 24
      chemical standards. The total concentrations in the studied samples ranged from
      20.56 to 88.56MUg/g. Phenolic acids were the most abundant class, accounting for
      76.2-90.4%, with benzoic acid, found at up to 18.87MUg/g. The concentration of
      catechins, typical of tea polyphenols, ranged between 2.1% and 9.7%, while the
      other flavonoids varied from 4.2% to 17.8%. Although the cultivation region
      affected the phenolic composition of the Camellia seed oils, in our hierarchical
      clustering analysis, the samples clustered according to species. The phenolic
      composition of the seed oils from C. oleifera and C. chekiangoelosa were similar.
      We found that the phenolic categories in Camellia seed oils were similar to tea
      polyphenols, thereby identifying a source of liposoluble tea polyphenols and
      potentially accounting for some of the reported activities of these oils. In
      addition, this work provides basic data that allows distinction of various
      Camellia seed oils, as well as improvements to be made in their quality
      standards.

PMID- 29195940
TI  - Formation of complexes between tannic acid with bovine serum albumin, egg
      ovalbumin and bovine beta-lactoglobulin.
AB  - Tannic acid (TA) shows strong interactions with proteins and the resulting
      complexes can be utilized as delivery systems for oral drugs. The complexation of
      TA with three proteins including bovine serum albumin (BSA), egg ovalbumin (EA)
      and bovine beta-lactoglobulin (BLG) at pH 7.4 was studied. The tryptophan (Trp)
      fluorescence of all three proteins was quenched by TA in a static quenching
      mechanism. BLG showed the highest binding affinity and a smallest binding
      distance with TA which may suggest that BLG-TA is the most stable complex. The
      results of circular dichroism, synchronous and three-dimensional fluorescence
      spectra suggested that the protein structures have been changed at different
      levels and helix structure was affected more significant than beta-strand. Zeta
      potential of all three proteins was more negative after binding with TA, which is
      favorable for the stabilization of protein based nanoparticles. Information
      derived from this work could be important to potentially use TA-protein complexes
      as nanoencapsulation systems for oral drug delivery.

PMID- 29195941
TI  - A new method to determine the water activity and the net isosteric heats of
      sorption for low moisture foods at elevated temperatures.
AB  - In recent years, research studies have shown that the thermal resistance of
      foodborne pathogens in the low moisture foods is greatly influenced by the water
      activity (aw) at temperatures relevant to thermal treatments for pathogen
      control. Yet, there has been a lack of an effective method for accurate
      measurement of aw at those temperatures. Thus, the main aim of this study was to
      evaluate a new method for measuring aw of food samples at elevated temperatures.
      An improved thermal cell with a relative humidity and temperature sensor was used
      to measure the aw of the three different food samples, namely, organic wheat
      flour, almond flour, and non-fat milk powder, over the temperature range between
      20 and 80 degrees C. For a constant moisture content, the aw data was used to
      estimate the net isosteric heat of sorption (qst). The qst values were then used
      in the Clausius Clapeyron equation (CCE) equation to estimate the moisture
      sorption isotherm for all test food samples at different temperatures. For all
      the tested samples of any fixed moisture content, aw value generally increased
      with the temperature. The energy for sorption decreased with increasing moisture
      content. With the experimentally determined qst value, CCE describes well about
      the changes in aw of the food samples between 20 and 80 degrees C. This study
      presents a method to obtain aw of a food sample for a specific moisture content
      at different temperatures which could be extended to obtain qst values for
      different moisture contents and hence, the moisture sorption isotherm of a food
      sample at different temperatures.

PMID- 29195942
TI  - Protective effect of mulberry fruit anthocyanin on human hepatocyte cells (LO2)
      and Caenorhabditis elegans under hyperglycemic conditions.
AB  - Type 2 diabetes is a chronic disease and hyperglycemia is important in the
      pathogenesis of diabetic complications. Exposure of LO2 cells to high glucose
      resulted in cellular glucose consumption and uptake decreases, reactive oxygen
      species (ROS) and superoxide anion (O2-) accumulation and mitochondrial
      dysfunction, which could be partly recovered by mulberry anthocyanin extract
      (MAE). And these protective effects were partly associated with regulation of
      nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets. As
      the insulin-signaling pathway is evolutionarily well conserved from
      Caenorhabditis elegans to mammals, C. elegans has been considered as a model
      system to study effects of glucose toxicity. Glucose shortened the lifespan of C.
      elegans, while MAE suppressed the damage, accompanied by malondialdehyde (MDA)
      and triglyceride accumulation reduction as well as total superoxide dismutase
      (SOD) and glutathione peroxidase (GPx) activity recovery and PMK-1/p38 expression
      promotion. In contrast, MAE failed to recover shortened longevity, glucose and
      triglyceride accumulation in daf-2 (-) mutants fed a glucose-supplemented diet.
      Transcriptional profile revealed MAE intervention led to 92 genes alteration
      compared with the glucose-treatment. Interestingly, expressions of DAF-2/insulin
      receptor related genes were increased by glucose but impaired by MAE in
      nematodes. Our studies suggested that MAE might help to improve the antioxidant
      defense system, resulting in prevention of glucose-induced damage both in vitro
      and in vivo.

PMID- 29195943
TI  - Interaction mode of calcium-binding peptides and Caco-2 cell membrane.
AB  - In our previous studies, soluble soybean protein hydrolysate (SPH)-calcium
      complexes were shown to promote the calcium uptake of Caco-2 cells. However, the
      calcium transport mode involved remains unknown. In this article, several
      experiments were carried out via cytological analysis to investigate the calcium
      transport mode of peptides with low calcium binding capacities (F1), peptides
      with high calcium-binding capacities (F2), and their separate calcium complexes
      (F1-Ca and F2-Ca) when interacting with cell membranes. The interaction between
      one of them and a cell membrane is the first step in intracellular transport, as
      indicated by fluorescence blue shift experiments and acrylamide quenching
      experiments. The results of zeta potential experiments showed that only the
      "charge neutralization" phenomenon occurs when the F1 peptide or F1-Ca complex
      interacts with cell membranes and thus cannot be transported into cells. On the
      contrary, in an F2 at high concentrations or F2-Ca complex, a "charge recovery"
      phenomenon occurs apart from "charge neutralization" and can thus be transported
      into cells through endocytosis.

PMID- 29195944
TI  - Fresh produce and their soils accumulate cyanotoxins from irrigation water:
      Implications for public health and food security.
AB  - Microcystin (MC), a hepatotoxin that can adversely affect human health, has
      become more prevalent in freshwater ecosystems worldwide, owing to an increase in
      toxic cyanobacteria blooms. While consumption of water and fish are well
      documented exposure pathways of MCs to humans, less is known about the potential
      transfer to humans through consumption of vegetables that have been irrigated
      with MC-contaminated water. Likewise, the impact of MC on the performance of food
      crops is understudied. To help fill these information gaps, we conducted a
      controlled laboratory experiment in which we exposed lettuce, carrots, and green
      beans to environmentally relevant concentrations of MC-LR (0, 1, 5, and 10MUg/L)
      via two irrigation methods (drip and spray). We used ELISA and LC-MS/MS to
      quantify MC-LR concentrations and in different parts of the plant (edible vs.
      inedible fractions), measured plant performance (e.g., size, mass, edible leaves,
      color), and calculated human exposure risk based on accumulation patterns. MC-LR
      accumulation was positively dose-dependent, with it being greater in the plants
      (2.2-209.2MUg/kg) than in soil (0-19.4MUg/kg). MC-LR accumulation varied among
      vegetable types, between plant parts, and between irrigation methods. MC-LR
      accumulation led to reduced crop growth and quality, with MC-LR persisting in the
      soil after harvest. Observed toxin accumulation patterns in edible fractions of
      plants also led to estimates of daily MC-LR intake that exceeded both the chronic
      reference dose (0.003MUg/kg of body weight) and total daily intake guidelines
      (0.04MUg/kg of body weight). Because the use of MC-contaminated water is common
      in many parts of the world, our collective findings highlight the need for
      guidelines concerning the use of MC-contaminated water in irrigation, as well as
      consumption of these crops.

PMID- 29195945
TI  - Theoretical study of aerobic vitamin C loss kinetics during commercial heat
      preservation and storage.
AB  - The non-isothermal aerobic degradation of ascorbic acid (AA), and the formation
      and subsequent degradation of the dehydroascorbic acid (DHAA) are described by
      two simultaneous rate equations, assuming that all three underlying reactions
      follow first or other fixed order kinetics. Also assumed is that the temperature
      dependence of these three reactions' rate-constants follows the exponential
      model, a simpler substitute for the traditional Arrhenius equation. The effective
      momentary vitamin C's concentration is assumed to be the sum of the AA's and
      DHAA's momentary concentrations. Plots of the rate equations' numerical solutions
      for non-isothermal temperature histories, such as those that exist in actual heat
      preservation processes and commercial storage of foods, allow examining the
      temperature regime's role in the vitamin C's retention, at least qualitatively,
      and to evaluate its loss pattern when DHAA is initially absent or already present
      in the food. The temperature profile can be expressed algebraically or as an
      interpolating function constructed for digitized data. With the generalized
      model's version, characterization of the vitamin loss kinetics may require at
      least nine independent parameters, which ought to be known a priori, assumed on
      the basis of literature reports or determined experimentally. However, for many
      practical applications the number of kinetic parameters can be reduced to six.
      Isothermal loss is a special case, which can be used to test the calculation
      procedure by comparing the numerical solutions for quasi-isothermal temperature
      histories with the analytical solutions for truly isothermal temperature
      profiles. A version of the calculation and simulation procedure has been posted
      on the Internet as a freely downloadable interactive Wolfram Demonstration, which
      can be used as a tool to examine the effect of actual and hypothetical
      temperature histories on the vitamin's retention during heat processing and
      storage. It can also be used to assess the impact of deviations from the assumed
      kinetic order and variability in the model's kinetic parameters on the vitamin's
      retention pattern.

PMID- 29195946
TI  - Rennet-induced coagulation properties of yak casein micelles: A comparison with
      cow casein micelles.
AB  - It is essential for yak cheese processing to understand the rennet-induced
      coagulation properties of gel formation from casein micelles. We have previously
      discovered that yak milk requires a longer incubation time but forms stronger
      gels compared with cow milk. In this study, we are aiming to understand the
      rennet-induced coagulation properties of yak casein micelles comparing with cow
      casein micelles. Rheological analyses revealed that the gelling times of yak and
      cow casein micelles were 11.6+/-0.5 and 8.7+/-0.4min (P<0.05) respectively, but
      yak casein gel had a higher elastic modulus G' (6.5+/-0.2Pa) than cow casein gel
      (2.5+/-0.2Pa; P<0.05). This is consistent with the results obtained by micro
      rheology. Confocal laser scanning microscopic images (CLSM) and cryo-scanning
      electron microscopic images (cryo-SEM) showed that yak casein gel was more
      homogeneous and had smaller pore size than cow casein gels. Yak casein micelles
      had higher calcium (26.00mM), phosphate (19.90mM) and beta-casein (relative 32%)
      concentrations. In addition, yak casein micelles were larger (Z-average 218.6nm)
      than cow casein micelles, and contained lower kappa-casein (relative 13%). By
      comparison with cow casein micelles, yak casein micelle composition corresponding
      to their micellar calcium phosphate and kappa-casein content may greatly
      contribute to the longer coagulation time and denser gel structure. An initial
      slower caseinomacropeptide (CMP) release rate and the slower rate of aggregation
      between para-casein micelles contributed to a more homogeneous yak gel network.
      Higher colloidal calcium phosphate is crucial for yak casein micelle aggregation
      and gel firmness because sufficient colloidal calcium phosphates can firmly glue
      sub-micelles and links casein micelles. This study provides valuable information
      for yak cheese production.

PMID- 29195947
TI  - Solubilization of industrial grade plant protein by enzymatic hydrolysis
      monitored by vibrational and nuclear magnetic resonance spectroscopy: A
      feasibility study.
AB  - Protein hydrolysates are of great interest in the food industry due to their
      nutritional and functional properties, but their use often implies solubilization
      in water and therefore hamper the use of plant proteins with inherent low water
      solubility. Protein solubility in water can be modified by enzymatic hydrolysis,
      but during this process several collateral properties of the protein hydrolysates
      changes. It is therefore important to determine the end-point of the process and
      to monitor its development. In this feasibility study, we demonstrated the
      potential of different spectroscopic techniques (1H NMR and IR) coupled with
      chemometrics analysis in monitoring the hydrolysis of five different industrial
      grade plant proteins by the enzyme Alcalase. Logarithmic modeling of the PCA
      (Principal Component Analysis) scores confirmed that they can represent a
      measurement of the solubilized protein material released and resulted in kinetic
      parameters describing the suitability of protein sources as substrates for the
      hydrolysis. This way, we showed that a qualitative evaluation of the degree of
      hydrolysis is possible using fast at-line technologies and PCA.

PMID- 29195948
TI  - Effects of soil type and organic fertilizers on fatty acids and vitamin E in
      Korean ginseng (Panax ginseng Meyer).
AB  - This study examined the effects of soil type and fertilizer regimes on variations
      in fatty acids (FAs) and vitamin E (Vit-E) in 6-year-old ginseng roots. We
      observed significant variation in both FA and Vit-E contents owing to the type
      and quantity of organic fertilizer used in each soil type during cultivation.
      Unsaturated FAs were approximately 2.7-fold higher in ginseng than in saturated
      FAs. Linoleic, palmitic, and oleic acids were the most abundant FAs detected in
      ginseng roots. Additionally, alpha-tocopherol was the major Vit-E detected. In
      particular, the increased application of rice straw compost or food waste
      fertilizer elevated the quantity of nutritionally desirable FAs and bioactive Vit
      E in ginseng root. Partial least square-discriminant analysis (PLS-DA) score
      plots showed that soil type might be the main cause of differences in FA and Vit
      E levels in ginseng. Specifically, the PLS-DA model indicated that palmitic acid
      is a suitable FA marker in determining whether ginseng plants were grown in a
      paddy-converted field or an upland field. Moreover, linoleic acid levels were
      highly correlated with alpha-linolenic acid (r=0.8374; p<0.0001) according to
      Pearson's correlations and hierarchical clustering analysis. Hence, these
      preliminary results should prove useful for the reliable production of ginseng
      containing high phytonutrient quantities according to cultivation conditions.

PMID- 29195949
TI  - Characterization of binding interaction between rice glutelin and gallic acid:
      Multi-spectroscopic analyses and computational docking simulation.
AB  - Many foods contain mixtures of plant dietary proteins and polyphenols, but there
      is currently a relatively poor understanding of the nature of the interactions
      between these components. In this study, the interaction of rice glutelin (RG)
      and gallic acid (GA) was characterized by spectroscopic and molecular docking
      techniques. The intrinsic fluorescence of RG quenched after the addition of GA,
      indicating that an interaction occurred. Thermodynamic analyses indicated that
      the binding process was spontaneous and the main driving forces were hydrogen
      bonds and van der Waals forces. The surface hydrophobicity of RG decreased with
      increasing GA. Furthermore, synchronous fluorescence and circular dichroism
      spectra provided insights into micro-environmental and conformational changes of
      RG. In particular, there was a reduction of alpha-helix structure and an increase
      of beta-sheet structure present in RG after the binding interaction. Finally,
      molecular docking analysis provided a visual representation of a single binding
      site where GA interacted with specific amino acid residues located in the active
      site of the RG.

PMID- 29195950
TI  - Fructooligosaccharides integrity after atmospheric cold plasma and high-pressure
      processing of a functional orange juice.
AB  - In this study, the effect of atmospheric pressure cold plasma and high-pressure
      processing on the prebiotic orange juice was evaluated. Orange juice containing
      7g/100g of commercial fructooligosaccharides (FOS) was directly and indirectly
      exposed to a plasma discharge at 70kV with processing times of 15, 30, 45 and
      60s. For high-pressure processing, the juice containing the same concentration of
      FOS was treated at 450MPa for 5min at 11.5 degrees C in an industrial equipment
      (Hyperbaric, model: 300). After the treatments, the fructooligosaccharides were
      qualified and quantified by thin layer chromatography. The organic acids and
      color analysis were also evaluated. The maximal overall fructooligosaccharides
      degradation was found after high-pressure processing. The total color difference
      was <3.0 for high-pressure and plasma processing. citric and ascorbic acid
      (Vitamin C) showed increased content after plasma and high-pressure treatment.
      Thus, atmospheric pressure cold plasma and high-pressure processing can be used
      as non-thermal alternatives to process prebiotic orange juice.

PMID- 29195951
TI  - Aggregation and rheological behavior of soluble dietary fibers from wheat bran.
AB  - The present study assesses the aggregation behavior of wheat bran arabinoxylan
      rich soluble dietary fiber (SDF) fractions with diverse molecular weight and
      substitution in order to provide useful information to prevent the formation of a
      block network. In the present work, dynamic and static light scattering,
      diffusing wave spectroscopy, small amplitude dynamic rheology, atomic force
      microscopy, and the water-holding and swelling capacities were evaluated to
      assess the SDF aggregation behavior induced by intrinsic and extrinsic factors.
      Furthermore, the rheological behavior was explained by the physically cross
      linked or interpenetrating hydrocolloid network established during SDF self
      aggregation, dependent on its molecular structure. The results indicated that the
      SDF fractions exhibiting a high molecular weight and a lower substitution degree
      and di-substituted ratio led to more significant aggregation due to the formation
      of disordered tangles coupled with a more solid-like behavior. The obtained
      information will prove useful for the development of more stable and compatible
      SDF fractions.

PMID- 29195952
TI  - The impact of cultivar on polyphenol and biogenic amine profiles in Calabrian red
      grapes during winemaking.
AB  - In this study, during winemaking, was evaluated the influence of cultivar on
      bioactive compounds (organic acids, d-(+)-glucose, d-(-)-fructose, biogenic
      amines (BAs), anthocyanins, polyphenols and flavonoids) and antioxidant activity
      of Calabrian (Southern Italy) autochthonous grapes (Arvino, Gaglioppo, Greco
      Nero, Magliocco Canino, Magliocco Dolce and Nocera). Phenolic compounds increased
      from grapes to wine for all varieties. Arvino grapevine showed the highest DPPH
      radical scavenging activity, while a promising inhibition of the lipid
      peroxidation was observed with Greco Nero grapes. BAs were mostly formed during
      alcoholic fermentation and Arvino always showed the lowest BAs amounts, while
      Magliocco Canino generally exhibited the highest. Collectively, the results
      demonstrated that Calabrian autochthonous grapevines were rich in sugars, organic
      acids and phenolic compounds thus allowing the production of high quality wines.

PMID- 29195953
TI  - Effect of glycation derived from alpha-dicarbonyl compounds on the in vitro
      digestibility of beta-casein and beta-lactoglobulin: A model study with glyoxal,
      methylglyoxal and butanedione.
AB  - alpha-Dicarbonyl compounds, which are widely found in common consumed food, are
      one of the precursors of advanced glycation end products (AGEs). In this study,
      the effect of glycation derived from glyoxal (GO), methylglyoxal (MGO) or
      butanedione (BU) on the in vitro digestibility of beta-casein (beta-CN) and beta
      lactoglobulin (beta-Lg) was investigated. Glycation from alpha-dicarbonyl
      compounds reduced the in vitro digestibility of studied proteins in both gastric
      and intestinal stage. In addition, glycation substantially altered the peptides
      released through gastric and gastrointestinal digestion, as detected by liquid
      chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-MS/MS).
      Crosslinked glycation structures derived from BU considerably reduced the
      sensitivity of glycated beta-Lg towards digestive proteases, albeit to a lesser
      degree in glycated beta-CN due to its intrinsic unordered structure. By contrast,
      non-crosslinked AGEs that formed adjacent to enzymatic cleavage sites did not
      block the enzymatic reaction in several cases, as evidenced by the corresponding
      digested peptides modified with glycation structures. These findings expand our
      understanding of the nutritional influence of alpha-dicarbonyl compounds and
      health impact of relevant dietary AGEs.

PMID- 29195954
TI  - Dehydration of jambolan [Syzygium cumini (L.)] juice during foam mat drying:
      Quantitative and qualitative changes of the phenolic compounds.
AB  - Jambolan [Syzygium cumini (L.)] berries are a popular fruit in Brazil, renowned
      for their high phenolic compound (PC) content. These PCs have antioxidant,
      antibacterial, and other characteristics that may be beneficial to human health.
      The objective of the study was to evaluate the quantitative and qualitative
      changes of the main phenolic compounds (PCs) (anthocyanins, flavonols, and
      hydrolysable tannins) in the jambolan fruit, the produced fruit juice, and in the
      corresponding dehydrated powders obtained by foam mat drying (60, 70, and 80
      degrees C) and lyophilization (control). The PCs were analyzed using high
      performance liquid chromatography with a diode array detection coupled with an
      electrospray ionization mass spectrometry (HPLC-DAD-ESI-MSn). Juice production
      resulted in a more pronounced degradation of anthocyanins than flavonols, and
      facilitated the extraction of hydrolysable tannins. Elevation of the dehydration
      temperature negatively impacted the anthocyanin content of the products; on the
      other hand, the flavonols and hydrolysable tannins were more sensitive to
      oxidation and heating time during dehydration, respectively, than dehydration
      temperature. In summary, it can be concluded that processing at 70 degrees C is
      most suitable, in light of the least loss of nutritional quality of the product
      with processing time. This study directly informs further investigations into
      preparation of high-quality jambolan fruit products.

PMID- 29195955
TI  - New insights in integrated response mechanism of Lactobacillus plantarum under
      excessive manganese stress.
AB  - As a natural inhabitant of gastrointestinal tract, Lactobacillus plantarum is
      well known for its health-promoting effects, especially in heavy metal-removal
      function. The response mechanism integrated physiology and proteomics of
      Lactobacillus plantarum under excessive manganese stress was systematically
      performed. More extracellular polymeric substance was secreted, whereas cells
      preferred to aggregate for resisting manganese stress. The stability of the
      membrane was maintained by up-regulating the proportion of unsaturated fatty
      acids, especially cyclopropane fatty acids. The contents of intracellular Asp and
      Arg, closely related with energy metabolism, decreased under excessive manganese
      stress. Comparative 2-DE proteomic analysis identified 52 proteins that
      significantly differed under different levels of manganese stress. The
      differentially expressed proteins, involved in the carbohydrate, amino acid,
      stress response and nucleotide metabolisms, were categorized as the crucial
      components during resisting manganese stress. Moreover, MntH 4 and MntH 5 were
      identified as the functional elements in regulation of manganese transportation
      model. The differential expression of six key transporter proteins under
      different manganese stresses indicated that the MntH 1, 2 and 3 was negatively
      regulated by MntR, while the regulation of MntH 4 and 5 presented the contrary
      model. Taken altogether, the study provides new insights into the response
      mechanism of probiotics to similar environmental stress.

PMID- 29195956
TI  - Different inoculation methods for semi-dry processed coffee using yeasts as
      starter cultures.
AB  - This study evaluates the behavior of Saccharomyces (S.) cerevisiae (CCMA 0543),
      Candida (C.) parapsilosis (CCMA 0544), and Torulaspora (T.) delbrueckii (CCMA
      0684) as starter cultures for semi-dry processed coffee using two inoculation
      methods: (1) direct inoculation and (2) bucket inoculation. The microbial
      population was evaluated by plating and real-time polymerase chain reaction
      (qPCR). The microbial metabolic changes of both bucket and direct inoculation
      methods during fermentation were evaluated using high performance liquid
      chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS). A
      sensorial test was also carried out. Citric and succinic acids were detected
      throughout the fermentation period. Chlorogenic acid concentration levels were
      higher for the bucket method after roasting. Roasted coffee beans also had a
      higher caffeine concentration, with the exception of the T. delbrueckii
      (CCMA0684) assay. Acids, pyrazines and pyridines were the main volatile compounds
      in both green and roasted coffee beans. Coffee cupping results proved that both
      inoculation methods scored well in terms of coffee quality. The bucket method
      favored the permanence of the microorganisms during coffee processing, especially
      the treatment inoculated with S. cerevisiae.

PMID- 29195957
TI  - Effect of a commercial tannin on the sensorial temporality of astringency.
AB  - Astringency is a tactile sensation that is generated by a reduction in
      lubrication in the oral cavity and is generally attributed to the interaction of
      procyanidins or condensed tannins with salivary proteins. Several factors
      influence tannin-protein interactions, such as pH, alcohol, sweetness, oxygen and
      polyphenol content. A scarcely studied factor is the effect of the tannin content
      on the perception of astringency. The objective of this study was to evaluate the
      effect of different concentrations of commercial oenological tannin (COT) on the
      timing of the perception of astringency. For this model, a vinous solution
      enriched with three concentrations of COT was used. The samples were subjected to
      a storage period of three months. Additionally, a panel was trained in the
      perception of astringency in red wines using a method of temporal dominance of
      sensations (TDS). Astringency descriptors were selected, and the TDS method was
      used to characterize the astringency. The samples were evaluated using
      traditional descriptors in TDS and astringency descriptors in TDS. In traditional
      TDS curves, treatments with higher concentrations of COT showed a higher and more
      persistent dominance index in the descriptor astringency. Moreover, the stimulus
      duration variable increased as the COT level increased. Likewise, temporary
      astringency was dominant over alcohol. For astringency TDS, at low concentrations
      of COT, the soft and adhesive descriptors were dominant, whereas at high COT
      concentrations, aggressive and drying were perceived as the dominant descriptors.
      An increasing concentration of tannin in the vinous solution generated an
      increased duration and dominance of astringency and reduced the duration of the
      sensation of alcohol. Finally, the type of perceived astringency was closely
      related to the tannin concentration.

PMID- 29195958
TI  - Chlorogenic acids and flavonoid extraction during the preparation of yerba mate
      based beverages.
AB  - This study determined the content of chlorogenic acids (CA) and rutin during
      successive aqueous extraction of yerba mate for terere and chimarrao from four
      yerba mate types (smooth, native, traditional and coarse ground). Aqueous
      extracts were prepared aiming to simulate homemade procedure by partially
      (chimarrao) or completely (terere) immersing the herb into hot (chimarrao) or
      cold (terere) water (30 times consecutively). The content of CA and rutin in the
      aqueous extracts was compared to those in methanolic extracts (exhaustive
      extraction). Terere aqueous extracts gave higher amounts of all phenolic
      compounds (2.5 to 6 times higher than chimarrao). Among chimarrao, course-ground
      aqueous extracts had on average 15% more PC (phenolic compounds). By comparing
      the content in aqueous and methanolic extracts, after 30 successive extractions,
      on average 14% of the total amount of CA in yerba mate leaves and 9% of rutin
      were transferred to the chimarrao extracts, whereas terere achieved between 40%
      and 100% of transference. Thus, this study shows that CA and rutin are
      continuously extracted during the preparation of aqueous extracts of chimarrao
      and terere, favoring a high intake of these antioxidant species by consumers.

PMID- 29195959
TI  - Identifying and modeling meteorological risk factors associated with pre-harvest
      contamination of Listeria species in a mixed produce and dairy farm.
AB  - This study sought to investigate the prevalence of Listeria species (including L.
      monocytogenes) in a mixed produce and dairy farm and to identify specific
      meteorological factors affecting Listeria spp. presence. Environmental samples
      were collected monthly from locations within the mixed farm over 14months and
      were analyzed for Listeria spp. Meteorological factors were evaluated for their
      association with the presence of Listeria spp. by using logistic regression (LR)
      and random forest (RF). The developed LR model identified wind speed and
      precipitation as significant risk factors (P<0.05), indicating higher wind speed
      at day 2 prior to sampling and higher average precipitation over the previous
      25days before sampling increased the probability of isolation of Listeria spp.
      from the mixed farm. Results from RF revealed that average wind speed at day 2
      prior to sampling and average precipitation in the previous 25days before
      sampling were the most important factors influencing the presence of Listeria
      spp., which supported the findings from LR. These findings indicate that the
      occurrence of Listeria spp. was influenced by wind speed and precipitation,
      suggesting run-off and wind-driven dust might be possible routes of pathogen
      transmission in mixed farms. The developed LR and RF models, with robust
      predictive performances as measured by the area under the receiver operating
      characteristic curves, can be used to predict Listeria spp. contamination risk in
      a mixed farm under different weather conditions and can help with the evaluation
      of farm management practices and the development of control strategies aimed at
      reducing pre-harvest microbial contamination in a mixed farming system.

PMID- 29195960
TI  - Formulation and characterization of O/W nanoemulsions encapsulating high
      concentration of astaxanthin.
AB  - This study evaluates the effect of modified lecithin (ML) and sodium caseinate
      (SC) on the formulation, stability and bioaccessibility of astaxanthin (AXT)
      loaded oil-in-water (O/W) nanoemulsions. These nanoemulsions were formulated
      using high-pressure homogenization in four passes at 100MPa. The volume mean
      diameter (d4,3) of nanoemulsions produced by ML and SC were 163+/-5 and 144+/-12
      nm, respectively. The physiochemical stability of nanoemulsions was recorded at
      25 degrees C. The nanoemulsions prepared by ML were stable for 30 minutes against
      a wide range of pH and heating temperatures (60-120  degrees C). However, ML
      stabilized nanoemulsions showed droplet growth when treated at high NaCl
      concentrations. In comparison, droplet growth was observed in SC-stabilized
      nanoemulsions at pH4 and at high temperature treatment. However, SC-stabilized
      nanoemulsions were stable at high NaCl concentration (500 mM). The SC-stabilized
      nanoemulsions showed good physical and chemical stability (>70%) after 30 days of
      storage. The bioaccessibility of AXT in nanoemulsions was significantly higher in
      ML (33%) than in SC-stabilized nanoemulsions (6%), indicating a strong influence
      of emulsifier on bioaccessibility. These findings provide valuable information in
      designing nutritional products such as aqueous based AXT fortified beverages.

PMID- 29195961
TI  - Encapsulation of the therapeutic microbe Akkermansia muciniphila in a double
      emulsion enhances survival in simulated gastric conditions.
AB  - There is considerable attention for developing Akkermansia muciniphila as a new
      therapeutic microbe since it has shown to prevent diet-induced obesity and type 2
      diabetes in mice. However, A. muciniphila is sensitive to gastric conditions such
      as low pH and oxygen. Therefore, we explored the possibility of encapsulating A.
      muciniphila in a water-in-oil-in-water (W/O/W) double emulsion, to allow for
      protection during gastric passage and subsequent release in the small intestine.
      The bacteria were efficiently encapsulated in the inner emulsion droplets and
      remained entrapped during in vitro gastric digestion. The cells were then
      released in the simulated intestinal phase of the in vitro system. The viability
      of encapsulated cells was found to be higher when compared to cells dispersed in
      buffer, that had been subjected to similar mechanical process as the one
      conducted to prepare the emulsion systems. Surprisingly, the viability of the
      processed cells was even higher than that of the cells dispersed in buffer
      without processing, likely due to shear-induced stress tolerance. To conclude,
      encapsulation in a double emulsion seems to be a promising strategy to protect A.
      muciniphila during gastric passage in oral formulations.

PMID- 29195962
TI  - Safety evaluations and lipid-lowering activity of an Arthrospira platensis
      enriched diet: A 1-month study in rats.
AB  - Arthrospira platensis (A. platensis) is worldwide consumed as dietary supplement,
      but its use in the form of whole biomass for food purposes may raise toxicity
      concerns. The aim of this study was to preliminarily evaluate the safety of an A.
      platensis F&M-C256-enriched diet (20% (weight/weight) corresponding to 12g/kg
      body weight/day), administered to rats for 1month. A. platensis F&M-C256-enriched
      diet was well tolerated: behavior, body weight, food consumption and growth
      curves were not affected; no discomfort, no deaths and no physical signs related
      to the treatment were observed during the administration period; food daily
      consumption and apparent digestibility were comparable to those of the standard
      laboratory AIN-76 control diet. Daily water consumption and urine excretion were,
      on the contrary, significantly higher (27.18+/-1.24 vs 21.53+/-1.68ml and 12.63+/
      0.99 vs 7.00+/-1.29ml respectively), probably because of a slight increase in
      sodium intake in rats fed A. platensis F&M-C256-enriched diet. Biochemical
      markers of kidney and liver function were not varied but a significant increase
      in cholesterol-HDL and a decreased plasma triglycerides level was observed in
      rats fed A. platensis F&M-C256-enriched diet. These last changes were associated
      with an increased fecal lipids excretion and liver PPAR-alpha gene expression.
      These results indicate that A. platensis F&M-C256 is likely safe and well
      tolerated even at a high dosage in rodents and suggest that it may represent a
      promising functional food for preventing or even for managing dyslipidemias.

PMID- 29195963
TI  - Order and session size effects on treatment discrimination: Case study liking for
      Dulce de Leche.
AB  - This study aimed to evaluate the implications of the number of samples per
      panelist in experimental precision and relative efficiency of treatment
      comparisons when modelling order effects for Dulce de Leche samples using a
      Sudoku design. Precision is defined as small variance and relative efficiency is
      defined as smaller variance than other alternative. Both are related to
      increasing discrimination power. A series of 8 Sudoku 16*16 squares being 4
      randomized independently and 4 others in the reverse order, was designed to allow
      a linear model fitting to experiments of different sizes (orders 1 to 4, 1 to 8,
      1 to 12 and 1 to 16). Data from 112 panelists were kept. Responses were recorded
      using a nine-point hedonic scale. Data was analyzed using a mixed linear model
      panelist, order and treatment (sample) effects. Analysis has shown a pronounced
      order effect, showing a first sample effect overestimation. Moreover, it was
      noted that order effect was rather evidenced in the first four orders, making for
      a relatively more precise experiment than the ones using remaining samples.
      Therefore, the use of Sudoku can be a convenient strategy to organize smaller
      testing sessions that could result in efficient experiments, with small variance
      of the estimated averages or effects and needing a lot less panelists to make a
      design as efficient as the large one used. Moreover, Sudoku can also inspire an
      efficient design that allows different test sessions.

PMID- 29195964
TI  - Phenolics content, fruit flesh colour and browning in cultivated eggplant, wild
      relatives and interspecific hybrids and implications for fruit quality breeding.
AB  - Increasing the content in bioactive phenolics in the eggplant (Solanum melongena)
      fruit is of interest, but may result in enhanced browning. We evaluated six
      varieties of S. melongena, 22 accessions of wild related species and 42
      interspecific hybrids between cultivated eggplant and wild relatives for
      phenolics content, fruit flesh colour, polyphenol oxidase (PPO) activity, and
      fruit flesh browning. Wild relatives generally had a higher content in phenolics
      and a broader range of variation than cultivated eggplant. Chlorogenic acid was
      the predominant (>65.0%) phenolic acid in cultivated eggplant and its primary
      genepool wild ancestor S. insanum, while for the other wild species on average
      represented <50% of the chromatogram peak area. Fruit flesh colour was lighter in
      S. melongena than in the wild species, while PPO activity and browning was much
      higher in wild species of the secondary and tertiary genepools. Interspecific
      hybrids between S. melongena and S. insanum were intermediate in their
      characteristics, while those with secondary and tertiary genepool species were
      more similar to the wild species. No significant correlations were found between
      total phenolics or chlorogenic acid contents and fruit flesh browning, but PPO
      activity was correlated to both the degree of browning (r=0.404) and colour
      difference (r=0.458). The results indicate that wild species can contribute to
      improving the bioactive properties of eggplant without affecting negatively fruit
      flesh colour and browning.

PMID- 29195965
TI  - Effect of atmospheric cold plasma (ACP) with its extended storage on the
      inactivation of Escherichia coli inoculated on tomato.
AB  - The study investigated the efficacy of atmospheric cold plasma (ACP) treatment on
      inactivation of E. coli load during extended storage period of 48h at both the
      temperatures of refrigeration (4 degrees C) as well as room (25 degrees C). The
      tomato samples were spot inoculated with E. coli and exposed to ACP at 15 and
      60kV for 5, 10, 15, and 30min followed by their storage at 4 degrees C and 25
      degrees C. The highest log reduction of 6logCFUmL-1 was achieved in population of
      E. coli after 15min of ACP treatment at 60kV, which was sustained up to storage
      duration of 48h at both the temperatures. Furthermore, significant reduction in
      E. coli was found at plasma treatment of 60kV in comparison to 15kV. The
      inactivation of E. coli was significantly (p<0.01) affected by combination of
      treatment higher voltage at extended treatment time, however, treatment time with
      prolonged storage of sealed ACP treated tomato was observed as a key factor in
      reduction of E. coli. In addition, investigation of E. coli exposed tomato
      surface was done using scanning electron microscopy that clearly showed the
      breakdown of cell cover of E. coli as a consequence of ACP. The study predicts
      the promising potential of the technique in sanitization of vegetables that are
      eaten raw like tomato.

PMID- 29195966
TI  - Thermal stability of reconstituted milk protein concentrates: Effect of partial
      calcium depletion during membrane filtration.
AB  - Milk protein concentrate (MPC) powders are increasingly utilized in manufacturing
      of protein fortified beverages. Thermal stability of the protein dispersions is
      of significant importance in such applications. It is known that a decrease in pH
      can induce partial dissociation of casein micelles and modify the natural
      equilibrium of calcium and phosphate between the micelles and the serum phase.
      The presence of soluble casein may improve the rehydration properties of MPC
      powders, and may impact their thermal stability. The objective of this work was
      to investigate the effects of partial acidification of milk prior to
      ultrafiltration on the heat stability of reconstituted MPC dispersions. Milk
      protein concentrate powders were prepared from skim milk acidified to pH6.0 by
      addition of glucono-delta-lactone, and then concentrated using ultrafiltration
      (UF) and diafiltration (DF). The heat stability of the reconstituted MPC
      dispersions was studied, by determining heat coagulation time, particle size,
      turbidity, viscosity, soluble and colloidal calcium and phosphate, and non
      sedimentable casein both before and after heating at 120 degrees C. Reconstituted
      MPC powders made with partially acidified skim milk contained lower soluble
      calcium and phosphate and exhibited very poor thermal stability compared to MPC
      powders made with skim milk at its natural pH. The thermal stability of the
      acidified MPC dispersions was not only recovered by restoration of pH and the
      serum composition through dialysis against skim milk, but it was improved
      compared to control MPC dispersions. All dialyzed samples had comparable pH,
      protein content and calcium and phosphate concentration, but the structure of the
      casein micelles was altered, causing differences in the type of soluble
      aggregates. It was concluded that the integrity of the casein micelles and the
      amount of dissociated, non-sedimentable caseins play a major role in determining
      the thermal stability of the MPC dispersions.

PMID- 29195967
TI  - Thermal effusivity measurement of conventional and organic coffee oils via
      photopyroelectric technique.
AB  - In this work, oil samples extracted from organic and conventional coffee beans
      were studied. A fatty acids profile analysis was done using gas chromatography
      and physicochemical analysis of density and acidity index to verify the oil
      purity. Additionally, Mid-Infrared Fourier Transform Photoacoustic Spectroscopy
      (FTIR-PAS) aided by Principal Component Analysis (PCA) was used to identify
      differences between the intensities of the absorption bands related to functional
      groups. Thermal effusivity values between 592+/-3 and 610+/-4Ws1/2m-2K-1 were
      measured using the photopyroelectric technique in a front detection
      configuration. The acidity index was between 1.11 and 1.27% and the density
      changed between 0.921 and 0.94g/mL. These variables, as well as the extraction
      yield between 12,6 and 14,4%, showed a similar behavior than that observed for
      the thermal effusivity, demonstrating that this parameter can be used as a
      criterion for discrimination between oil samples extracted from organic and
      conventional coffee beans.

PMID- 29195968
TI  - Sensory characterization of the astringency of commercial Uruguayan Tannat wines.
AB  - Astringency is one of the most important characteristics that define the quality
      of red wine, and is of particular relevance for Tannat, Uruguayan emblematic red
      wine variety. Astringency is a time-dependant and complex sensory characteristic,
      related to several sensations, or sub-qualities, that can be simultaneously
      perceived. The aim of the present study was to obtain a sensory characterization
      of the astringency of commercial Uruguayan Tannat wines. Forty samples with
      different characteristics in terms of vintage, price segment and aging in oak
      barrels were assessed by a panel of 9 trained assessors. Total astringency
      intensity was evaluated using time-intensity (TI), while astringency sub
      qualities were described using a check-all-that-apply (CATA) question composed of
      sixteen terms. TI and the CATA question provided different information on the
      astringency of Tannat wines. Regarding global astringency, samples mainly
      differed in intensity-related parameters rather than in the development of
      astringency over time, although the variability was moderate. A wide range of sub
      qualities, from silky and velvety to harsh and aggressive were used to describe
      the astringency of the evaluated wines. Four groups of samples with different
      astringency characteristics were identified, but this sorting was not related to
      vintage, price segment or aging in oak barrels. Further research is necessary to
      better understand how astringency characteristics are influenced by production
      variables, and to understand their relationship to consumers' and experts'
      perceived quality of Tannat wines.

PMID- 29195969
TI  - Rapid methodology via mass spectrometry to quantify addition of soybean oil in
      extra virgin olive oil: A comparison with traditional methods adopted by food
      industry to identify fraud.
AB  - Fast and innovative methodology to monitors the addition of soybean oil in extra
      virgin olive oil was developed employing ESI-MS with ionization operating in
      positive mode. A certified extra virgin olive oil and refined soybean oil samples
      were analyzed by direct infusion, the identification of a natural lipid marker
      present only in soybean oil (m/z 886.68 [TAG+NH4]+) was possible. The certified
      extra virgin olive oil was purposely adulterated with soybean oil in different
      levels (1, 5, 10, 20, 50, 70, 90%) being possible to observe that the new
      methodology is able to detect even small fraud concentration, such as 1% (v/v).
      Additionally, commercial samples were analyzed and were observed the addition of
      soybean oil as a common fraud in this segment. This powerful analytical method
      proposed could be applied as routine analysis by control organization, as well as
      food industries, considering its pronounced advantages; simplicity, rapidity,
      elevated detectability and minor amounts of sample and solvent consumed.

PMID- 29195970
TI  - Protection of resveratrol against the photodecomposition of folic acid and
      photodecomposition-induced structural change of beta-lactoglobulin.
AB  - Folic acid is a synthetic form of the B-group vitamin known as folate and
      essential for a variety of physiological processes. However, it decomposes under
      UV irradiation, causing indirect oxidation and structural change of protein. In
      this study, the protective effect of resveratrol against the photodecomposition
      of folic acid and its caused protein structural change was investigated by using
      fluorescence and absorbance spectroscopy, high performance liquid chromatography
      and ABTS assay. It was found that resveratrol could inhibit the folic acid
      decomposition and control the decomposition process, depending on the polyphenol
      concentration and addition time. Transformation of resveratrol was accelerated by
      photodecomposition of folic acid. Antioxidant activity of resveratrol was
      important for the protective effect. Moreover, resveratrol could also inhibit the
      unfolding of beta-lactoglobulin caused by the folic acid decomposition by using
      circular dichroism.

PMID- 29195971
TI  - Effects of dietary replacement of fishmeal by mealworm meal on muscle quality of
      farmed shrimp Litopenaeus vannamei.
AB  - This study investigated the muscle quality of the shrimp Litopenaeus vannamei fed
      on a diet containing different proportions of mealworm meal (MW) (0, 25, 50, 75
      and 100%) as a substitute for fishmeal, which is the normal diet used in shrimp
      commercial production. The proximate composition, fatty acid profile, colour and
      texture of the shrimps were evaluated. Moisture, protein, and ash content of
      shrimp muscle were not significantly altered when fishmeal was replaced by MW
      (p>0.05). However, the replacement resulted in a linear increase in lipid content
      (p<0.05). The fatty acid composition of the experimental diets directly mirrored
      the fatty acid composition of shrimp muscle. The absence of long-chain
      polyunsaturated fatty acids in MW composition resulted in a linear decrease in
      eicosapentaenoic and docosahexaenoic fatty acids in shrimp muscle with increasing
      levels of MW in the diet. The n-3/n-6 ratio ranged from 0.50 to 0.67. Colour and
      firmness were unchanged between the treatments. Although the use of MW as a
      fishmeal substitute in L. vannamei diets has affected the lipid and fatty acid
      composition of shrimp muscle, from a human nutritional perspective, the lipid
      content of the shrimps is considered low and the n-3/n-6 ratio remained within
      the human dietary requirements. Therefore the use of a mealworm diet for shrimp
      production is a viable alternative to increasingly expensive fishmeal based
      diets.

PMID- 29195972
TI  - Impact of phenylalanine and urea applications to Tempranillo and Monastrell
      vineyards on grape amino acid content during two consecutive vintages.
AB  - Nitrogen plays a key role in the fermentation and secondary metabolites
      formation. The aim was to study the influence of vine nitrogen applications on
      grape amino acid composition. Nitrogen sources applied to Tempranillo and
      Monastrell grapevines were phenylalanine and urea, during two seasons. Results
      showed that the application of these compounds had little effect on grape amino
      acid composition, regardless of variety and vintage. This could be due to the
      fact that vineyards did not present nitrogenous requirements. Thus, variety was
      the determining factor in Asp, Glu, Gln, Cit, Met, Gly, Gaba, Val, Ile, and Leu
      while season was the factor that most affected Thr, Arg, Ala, and Lys due its
      implication on berry ripening. The concentration of the remaining amino acids was
      influenced by two or three of the factors studied. Therefore, when the vineyard
      has adequate nitrogen nutritional status, grape amino acid content was determined
      by variety and vintage.

PMID- 29195973
TI  - Microstructure and physicochemical properties reveal differences between high
      moisture buffalo and bovine Mozzarella cheeses.
AB  - Mozzarella cheese is a classical dairy product but most research to date has
      focused on low moisture products. In this study, the microstructure and
      physicochemical properties of both laboratory and commercially produced high
      moisture buffalo Mozzarella cheeses were investigated and compared to high
      moisture bovine products. Buffalo and bovine Mozzarella cheeses were found to
      significantly differ in their microstructure, chemical composition, organic acid
      and proteolytic profiles but had similar hardness and meltability. The buffalo
      cheeses exhibited a significantly higher ratio of fat to protein and a
      microstructure containing larger fat patches and a less dense protein network.
      Liquid chromatography mass spectrometry detected the presence of only beta-casein
      variant A2 and a single beta-lactoglobulin variant in buffalo products compared
      to the presence of both beta-casein variants A1 and A2 and beta-lactoglobulin
      variants A and B in bovine cheese. These differences arise from the different
      milk composition and processing conditions. The differences in microstructure and
      physicochemical properties observed here offer a new approach to identify the
      sources of milk used in commercial cheese products.

PMID- 29195974
TI  - Colorimetric study of malvidin-3-O-glucoside copigmented by phenolic compounds:
      The effect of molar ratio, temperature, pH, and ethanol content on color
      expression of red wine model solutions.
AB  - In the recent research, the copigmentations of malvidin-3-O-glucoside with eight
      types of phenolic copigments have been investigated. The influence of the
      pigment/copigment molar ratio, the reaction temperature, the pH and the ethanol
      content of solutions has been examined. The results showed that the
      copigmentation effect was dependent on not only the particular structures of the
      phenolic compounds but also the factors of the reaction systems. The increase of
      the copigment concentration can strengthen the copigmentation effect, improve the
      solution color, and enhance the red-purple features. Different temperatures had
      different influences on the copigmentation reactions. The destruction of the
      copigmentation complexes can result in the hypsochromic shift of the reaction
      solution when the temperature was higher than 20 degrees C. The bathochromic
      shift of the solution gradually progressed with the increase of the pH value. A
      significant copigmentation feature was spotted when pH reached 3.0, which
      demonstrates obvious red-purple characterization. The addition of the ethanol
      weakened the copigmentation effect. According to measurement through color
      analysis, it was found that the color differences caused by ethanol in red wine
      were typically attributed to quantitative changes. Remarkably, all of the above
      delicate color deviations caused by the structural or environmental factors can
      be precisely and conveniently depicted via the CIELAB space analysis.

PMID- 29195975
TI  - Exploring mouthfeel in model wines: Sensory-to-instrumental approaches.
AB  - Wine creates a group of oral-tactile stimulations not related to taste or aroma,
      such as astringency or fullness; better known as mouthfeel. During wine
      consumption, mouthfeel is affected by ethanol content, phenolic compounds and
      their interactions with the oral components. Mouthfeel arises through changes in
      the salivary film when wine is consumed. In order to understand the role of each
      wine component, eight different model wines with/without ethanol (8%), glycerol
      (10g/L) and commercial tannins (1g/L) were described using a trained panel.
      Descriptive analysis techniques were used to train the panel and measure the
      intensity of the mouthfeel attributes. Alongside, the suitability of different
      instrumental techniques (rheology, particle size, tribology and microstructure,
      using Transmission Electron Microscopy (TEM)) to measure wine mouthfeel sensation
      was investigated. Panelists discriminated samples based on their tactile-related
      components (ethanol, glycerol and tannins) at the levels found naturally in wine.
      Higher scores were found for all sensory attributes in the samples containing
      ethanol. Sensory astringency was associated mainly with the addition of tannins
      to the wine model and glycerol did not seem to play a discriminating role at the
      levels found in red wines. Visual viscosity was correlated with instrumental
      viscosity (R=0.815, p=0.014). Hydrodynamic diameter of saliva showed an increase
      in presence of tannins (almost 2.5-3-folds). However, presence of ethanol or
      glycerol decreased hydrodynamic diameter. These results were related with the
      sensory astringency and earthiness as well as with the formation of nano
      complexes as observed by TEM. Rheologically, the most viscous samples were those
      containing glycerol or tannins. Tribology results showed that at a boundary
      lubrication regime, differences in traction coefficient lubrication were due by
      the presence of glycerol. However, no differences in traction coefficients were
      observed in presence/absence of tannins. It is therefore necessary to use an
      integrative approach that combines complementary instrumental techniques for
      mouthfeel perception characterization.

PMID- 29195976
TI  - The effect of CaCl2 marination on the tenderizing pathway of goose meat during
      conditioning.
AB  - In order to figure out the effect of CaCl2 on the tenderizing pathway of goose
      meat, breast muscles of thirty-two Eastern Zhejiang White Geese were divided into
      three treatments: the control, 150 and 300mM CaCl2. Shear force, myofibrillar
      fraction index (MFI), actin filaments and F-actin, G-actin and tropomodulins
      (Tmods) levels were investigated during 168h. Results showed that 300mM treatment
      had lower shear force at 48, 96 and 168h and higher MFI at 24, 48, 96 and 168h
      than the control. The rate of actin filaments disruption, the decrease of F
      actin, the degradation of Tmods, the increase of G-actin in 300mM treatment was
      faster than 150mM treatment; the rate in the control was the slowest among
      treatments. CaCl2 accelerated the transformation of F-actin into G-actin. We
      concluded that CaCl2 tenderized goose meat by depolymerizing actin filaments and
      cleaving Tmods.

PMID- 29195977
TI  - Study the effects of drying processes on chemical compositions in daylily flowers
      using flow injection mass spectrometric fingerprinting method and chemometrics.
AB  - Daylily flowers is an important vegetable in eastern Asia, widely used in many
      dishes. Daylily flowers are usually sold in dried forms in the supermarkets.
      There are a few method for processing fresh daylily flowers, however, no study
      has been conducted to analyze the effects of the processing methods in the
      composition of final products. In the present study, a flow-injection mass
      spectrometric fingerprinting (FIMS) method in combination with principal
      component analysis (PCA) was used to differentiate two species of daylily flowers
      (Mengzi and Chongli) with three different treatments (vacuum freeze drying, solar
      drying and hot-air drying treatments) for each. The results showed the fast and
      simple FIMS method could successfully differentiate between species (raw
      material) and treatments among each species. However, the two species could not
      be discriminated very well after being processed in hot-air drying treatment. The
      difference in chemical profiles of species and treatments were discussed.

PMID- 29195978
TI  - Merging vibrational spectroscopic data for wine classification according to the
      geographic origin.
AB  - The wine making procedure is no longer a secret and it is nowadays well described
      and repeated around the world. Nevertheless, wines present unique features,
      strongly associated with their geographic origin. Classification systems were
      developed to catalogue wines according to the provenance, and are currently
      established by official authorities in order to ensure wine authenticity. The use
      of near-infrared (NIR), mid-infrared (MIR) and Raman spectroscopy for tracing the
      origin of wine samples, has been reported with different levels of success. This
      work evaluated and compared the performance of these techniques, as well as their
      joint use, in terms of geographic origin classification. NIR, MIR and Raman
      spectra of wine samples belonging to four Portuguese wine regions (Vinhos Verdes,
      Lisboa, Acores and Tavora-Varosa) were analyzed by partial least squares
      discriminant analysis (PLS-DA). Results revealed the better suitability of MIR
      spectroscopy (87.7% of correct predictions) over NIR (60.4%) and Raman (60.8%).
      The joint use of spectral sets did not improve the predictive ability of the
      models. The best models were achieved by combining MIR and NIR spectra resulting
      in 86.7% of correct predictions. Multiblock partial least squares (MB-PLS) models
      were developed to further explore the combination of spectral data. Although
      these models did not improve the percentage of correct predictions, they
      demonstrated the higher contribution of MIR spectroscopic data, in the
      development of the models.

PMID- 29195979
TI  - Analysis of the bacterial microbiome in the small octopus, Octopus variabilis,
      from South Korea to detect the potential risk of foodborne illness and to improve
      product management.
AB  - The small octopus (Octopus variabilis) is a popular seafood in many countries
      including South Korea. Because it is often consumed uncooked, the microorganisms
      in it often cause food poisoning. Therefore, analyzing the microbiome of the
      small octopus can help to understand the risk of food poisoning and manage
      octopus products better. A total of 40 small octopuses were collected from four
      sites in November and August. The microbiota was analyzed using Illumina Miseq
      sequencing, and the amount of bacteria was quantified by real-time PCR. In
      addition, we analyzed the influence of Vibrio vulnificus infection on the
      microbiome of the small octopus through artificial infection experiments.
      Bacteroidetes was the predominant phylum in August, and Proteobacteria was
      predominant in November. The composition of the microbiota in octopus depended on
      sampling region and season. The potential risk of foodborne illness from small
      octopus consumption might be higher in August than in November due to the
      abundance of potential pathogens. In the infection experiment, the proportion of
      V. vulnificus increased only at 27 degrees C. The composition and functional gene
      profiles of the microbiota varied in a similar manner between non-infected and
      infected samples over time at the same temperature. These results indicated that
      the indigenous microbiota in small octopus could inhibit colonization by V.
      vulnificus during storage. Although further studies are necessary to clarify
      these results, our results could help us better understand food poisoning through
      octopus ingestion and manage products.

PMID- 29195980
TI  - Comparative stability and efficacy of selected chlorine-based biocides against
      Escherichia coli in planktonic and biofilm states.
AB  - Microbial contamination is an unavoidable problem in industrial processes. Sodium
      hypochlorite (SH) is the most common biocide used for industrial disinfection.
      However, in view of the current societal concerns on environmental and public
      health aspects, there is a trend to reduce the use of this biocide as it can lead
      to the formation of organochlorinated carcinogenic compounds. In this work the
      efficacy of SH was assessed against Escherichia coli in planktonic and biofilm
      states and compared with three alternative chlorine-based biocides: neutral
      electrolyzed oxidizing water (NEOW), chlorine dioxide (CD) and sodium
      dichloroisocyanurate (NaDCC). The planktonic tests revealed that SH had the
      fastest antimicrobial action, NaDCC exhibited the highest antimicrobial rate and
      NEOW caused the highest antimicrobial effects. Additionally, NEOW was the biocide
      that allowed the highest formation of reactive oxygen species (ROS). In biofilm
      control, NEOW and CD were the most efficient biocides causing 3.26 and 3.20 log
      CFU.cm-2 reduction, respectively. In terms of stability for chlorine depletion,
      NEOW had the longest decay time for chlorine loss (70days at 5 degrees C) and the
      lowest chlorine loss rate (0.013ppm.min-1 at 5 degrees C). CD and NaDCC had
      equivalent stability. The overall results demonstrated NEOW as a good alternative
      to SH due to its higher antimicrobial effects and lower chlorine depletion over
      time.

PMID- 29195981
TI  - Stress adaptation has a minor impact on the effectivity of Non-Thermal
      Atmospheric Plasma (NTAP) against Salmonella spp.
AB  - This study was aimed at studying the influence of gas composition (air and
      nitrogen) at different flow rates (5, 10 and 15Lm-1) and stress adaptation
      (growth under a wide range of temperatures [10-45 degrees C] and acid conditions
      [up to pH4.5, using different organic acids] or short-term exposure to acid, cold
      or heat stress shocks) on the inactivation by Non-Thermal Atmospheric Plasma
      (NTAP) of S. Typhimurium CECT 443 and S. Enteritidis CECT 4300. Results obtained
      evidence that microbial inactivation was significantly higher when air was used
      for NTAP treatments. D-values obtained using air ranged from 0.86 to 2.43min and
      0.90 to 1.69min for S. Typhimurium and S. Enteritidis, respectively, while those
      obtained using nitrogen ranged from 3.08 to 5.75min and 2.28 to 5.54min,
      respectively. Microbial inactivation also increased with increasing flow rates,
      although differences were not statistically significant in all cases. Growth
      temperature and pH or exposure to acid, cold or heat stress shocks had a minor
      impact on NTAP resistance. Indeed, D-values obtained under the different stress
      adaptation scenarios were not significantly different from those obtained for non
      adapted control cultures (1.38+/-0.39 for S. Typhimurium and 1.23+/-0.36 for S.
      Enteritidis), with the exception of cells grown at 10 degrees C, which were
      significantly more sensitive to NTAP, with D-values of 0.68+/-0.11 and 0.45+/
      0.10min, respectively, for S. Typhimurium and S. Enteritidis. These findings
      suggest that adaptive responses triggered by exposure to acid, cold or heat
      stresses, already described in the past for these two Salmonella strains, do not
      provide protection against NTAP treatments, which allows us to conclude that NTAP
      may be a first-choice technology to be included into food processing schemes
      following a hurdles technology approach in combination with acidification, mild
      heating or refrigeration.

PMID- 29195982
TI  - High resolution mass approach to characterize refrigerated black truffles stored
      under different storage atmospheres.
AB  - Freshly harvested Tuber melanosporum samples were packed and stored at 4 degrees
      C under reduced atmospheric pressure or modified atmosphere for four weeks.
      Multivariate analysis was employed to correlate the antioxidant power of the
      ethanolic extracts of the samples with the chemical composition determined by
      high resolution mass spectrometry. High performance liquid chromatography coupled
      with a coularray detector was applied to select the chemical species associated
      with the antioxidant power. Four classes of chemical compounds were investigated
      in more detail by a targeted approach: derivatives of glutathione, adenine (such
      as S-adenosyl-homocysteine), oxidized linoleic acid and ergosterol. Adducts
      containing glutathione and adenine with oxidized linoleic acid were observed in
      TM for the first time and can be considered markers of freshness of the product.
      S-adenosyl-homocysteine, the acetyl-carnitine adduct with cysteinyl-glycine and
      several oxidized linoleic acid derivatives were among the markers of degradation.

PMID- 29195983
TI  - Comparative analysis of the volatile composition of honeys from Brazilian
      stingless bees by static headspace GC-MS.
AB  - The volatile composition of honeys produced by eight species of stingless bees
      collected in three municipalities in the state of Parana (Brazil) was compared by
      combining static headspace GC-MS and chemometrics methods. Forty-four compounds
      were identified using NIST library and linear retention index relative to n
      alkanes (C8-C40). Linalool derivatives were the most abundant peaks in most
      honeys regardless geographical or entomological origin. However, Principal
      Component Analysis discriminated honeys from different geographical origins
      considering their distinctive minor volatile components. Honey samples from
      Guaraquecaba were characterized by the presence of hotrienol while those from
      Cambara showed epoxylinalol, benzaldehyde and TDN as minor discriminating
      compounds. Punctual species such as Bora showed similar fingerprints regardless
      geographical origin, with ethyl octanoate and ethyl decanoate as characteristic
      intense chromatographic peaks, which may suggest a specialized behavior for
      nectar collection. Discriminant Analysis allowed correct geographic
      discrimination of most honeys produced in the three spots tested. We concluded
      that volatile profile of stingless bee honeys can be used to attest authenticity
      related to regional origin of honeys.

PMID- 29195984
TI  - Spatial (cap & stipe) metabolomic variations affect functional components between
      brown and white beech mushrooms.
AB  - The beech mushrooms have customarily been revered by oriental societies for their
      nutritional and health benefits. We explored the mass spectrometry (MS) based
      spatial metabolomic variations between parts (cap and stipe) of two beech
      mushroom strains (brown and white). The principal component analysis (PCA)
      revealed their distinct primary (cap and stipe: PC1, 25.5%; strains: PC2, 12.5%)
      and secondary (cap and stipe: PC1, 10.3%; strains: PC2, 7.6%) metabolite
      patterns. The caps were rich in amino acids, fatty acids, and N-acetylglucosamine
      with higher protein and nitrogen contents. The stipes had abundant beta-glucans,
      malic acid, and fructose. The discriminant secondary metabolites, especially,
      hypsiziprenols were higher in caps from brown strains. A fatty acid derivative,
      azelaic acid, was abundant in white strains (cap>stipe). We established a
      positive correlation for the cytotoxic activities of hypsiziprenols against ACHN
      cells. These spatial inter-strain metabolomic distinctions are potentially
      helpful for mushroom selection and improvement.

PMID- 29195985
TI  - What are the cultural effects on consumers' perceptions? A case study covering
      coalho cheese in the Brazilian northeast and southeast area using word
      association.
AB  - The aim of this study was to investigate the effects of regional diversity
      aspects related to consumers' perceptions of coalho cheese, with Brazilian
      Northeast and Southeast consumers (n=400, divided equally in each area) using
      Word Association (WA) task. Different perceptions were detected for both
      Northeast and Southeast consumers, and among 17 categories elicited for
      describing coalho cheese, only 7 categories (positive feeling, social aspects,
      sensory characteristic, dairy product technology, negative feeling, and lack of
      quality standard) presented significant differences in the frequency of mention
      according to chi-square per cell approach. The application of the discriminant
      technique Partial Least Square Discriminant Analysis (PLS-DA) indicated that the
      categories "Social", "Accompaniment", "Manufacturing method" were the main
      responsible for differentiating consumers' perceptions of both areas. Overall,
      the main dimensions involved in the consumers' perceptions of coalho cheese from
      different Brazilian regions were identified, thus obtaining comprehensive
      insights that can be used as a guideline for coalho cheese producers to develop
      marketing strategies considering the intra-cultural differences.

PMID- 29195986
TI  - Comparison of non-volatile umami components in chicken soup and chicken enzymatic
      hydrolysate.
AB  - Umami taste is an important part to the taste of chicken. To isolate and identify
      non-volatile umami compounds, fractions from chicken soup and hydrolysate were
      prepared and analyzed. Amino acids were analyzed by amino acid analyzer. Organic
      acids and nucleotides were determined by ultra-performance liquid chromatography.
      Separation procedures utilizing ultrafiltration, Sephadex G-15 and reversed-phase
      high-performance liquid chromatography were used to isolate umami taste peptides.
      Combined with sensory evaluation and LC-Q-TOF-MS, the amino acid sequences of 12
      oligopeptides were determined. The amount of taste compounds was higher in
      chicken enzymatic hydrolysate than that of chicken soup. Eight oligopeptides from
      chicken enzymatic hydrolysate were identified, including Ala-Asp, Ala-Met, His
      Ser, Val-Glu, Ala-Glu, Asp-Ala-Gly, Glu-Asp and Ala-Glu-Ala. Four oligopeptides
      from chicken soup were identified, including Val-Thr, Ala-His, Ala-Phe and Thr
      Glu.

PMID- 29195987
TI  - Physiological comparability of the harmonized INFOGEST in vitro digestion method
      to in vivo pig digestion.
AB  - Recently, a static in vitro digestion (IVD) protocol was published by Minekus and
      coworkers (Minekus et al., 2014) within the COST INFOGEST network. The protocol,
      concentrating on physiological enzyme activities had the main goal to improve the
      comparability of experimental data between labs. The protocol was validated in
      several inter-laboratory studies using skim milk powder (SMP) and indeed
      demonstrated improved harmonization compared with previous experiments with
      individual IVD protocols (Egger et al., 2016). Although the enzyme activities and
      salt concentrations of the harmonized protocol are based on available human in
      vivo data, confirmation of the protocol's physiological relevance has been
      lacking until now. The main goal of the study was therefore to compare the
      harmonized IVD protocol with data from in vivo digestion. Towards this aim, an in
      vivo pig experiment with the same SMP as used for the validation of the IVD
      protocol was performed followed by a comparison of protein hydrolysis between in
      vivo and in vitro results. Protein hydrolysis at different levels was analyzed
      with gel electrophoresis, mass spectrometry, high performance liquid
      chromatography, and spectrophotometric o-phthaldialdehyde determination of free
      amino acids. Principle component analysis was used for graphical data comparison.
      Milk proteins detected after gastric IVD corresponded to gastric and duodenal in
      vivo samples and intestinal IVD samples corresponded to distal jejunal in vivo
      samples. Peptides identified after the gastric phase of IVD, correlated with in
      vivo gastric samples (r=0.8) and intestinal IVD peptides correlated best with in
      vivo samples collected from the median jejunum (r=0.57). Free amino acids were in
      both systems mainly released during the intestinal phase of digestion. Protein
      hydrolysis in the harmonized IVD was similar to in vivo protein hydrolysis in
      pigs at the gastric and intestinal endpoints. Therefore, the harmonized static in
      vitro protocol is suited to study protein hydrolysis at these endpoints.

PMID- 29195988
TI  - Recent advances in microencapsulation of natural sources of antimicrobial
      compounds used in food - A review.
AB  - Food safety and microbiological quality are major priorities in the food
      industry. In recent years, there has been an increasing interest in the use of
      natural antimicrobials in food products. An ongoing challenge with natural
      antimicrobials is their degradation during food storage and/or processing, which
      reduces their antimicrobial activity. This creates the necessity for treatments
      that maintain their stability and/or activity when applied to food.
      Microencapsulation of natural antimicrobial compounds is a promising alternative
      once this technique consists of producing microparticles, which protect the
      encapsulated active substances. In other words, the material to be protected is
      embedded inside another material or system known as wall material. There are few
      reports in the literature about microencapsulation of antimicrobial compounds.
      These published articles report evidence of increased antimicrobial stability and
      activity when the antimicrobials are microencapsulated when compared to
      unprotected ones during storage. This review focuses mainly on natural sources of
      antimicrobial compounds and the methodological approach for encapsulating these
      natural compounds. Current data on the microencapsulation of antimicrobial
      compounds and their incorporation into food suggests that 1) encapsulation
      increases compound stability during storage and 2) encapsulation of antimicrobial
      compounds reduces their interaction with food components, preventing their
      inactivation.

PMID- 29195989
TI  - The influence of sweet pepper pectin structural characteristics on cytokine
      secretion by THP-1 macrophages.
AB  - Pectins can modulate the biological responses interacting directly with immune
      cells. The observed responses can strongly be affected by polysaccharide
      structural features. We analyzed the intrinsic activation capacity of native and
      modified sweet pepper pectin on cytokine secretion by THP-1 macrophages as well
      as compare their effects in the presence of lipopolysaccharide. Modified pectin
      was obtained by partial acid hydrolysis which promoted the removal of side chains
      as well as the reduction of molecular weight and the degree of methyl
      esterification of native pectin. The results showed that both fractions had no
      effect on THP-1 viability. Native pectin at 300MUg/mL increased TNF-alpha, IL
      1beta and IL-10 cytokine secretion by THP-1 macrophages. However, in the presence
      of lipopolysaccharide, it can attenuate the inflammatory response by reducing the
      production of the pro-inflammatory cytokines TNF-alpha and IL-1beta and
      increasing the anti-inflammatory cytokine IL-10, as well as decreasing the TNF
      alpha/IL-10 and IL-1beta/IL-10 ratios. The structural modifications caused by
      acid hydrolysis affected the intrinsic activation capacity of native pectin to
      modulate the cytokines secretion. These results indicate that degree of methyl
      esterification, molecular weight and presence of side chains are important
      structural features of pectins involved in the modulation of cytokine secretion
      by THP-1 macrophages.

PMID- 29195990
TI  - Extraction of bioactive compounds from genipap (Genipa americana L.) by
      pressurized ethanol: Iridoids, phenolic content and antioxidant activity.
AB  - The search for compounds with functional properties from natural sources has
      grown in recent years as people have developed healthier habits. Therefore, the
      aim of this study was to evaluate the extraction of bioactive compounds from
      various parts of unripe genipap fruit (Genipa americana L.) by using pressurized
      ethanol to verify which part of the fruit provides the greatest recovery of the
      iridoids genipin and geniposide. Two process variables were studied: temperature
      (50 and 80 degrees C) and pressure (2, 12 and 20 bar). The whole fruit and the
      peel, mesocarp, endocarp, endocarp+seeds and seeds of the fruit were studied. The
      endocarp presented with the highest recovery of genipin (48.6+/-0.6mg/g raw
      material) and the extraction from the mesocarp allowed a greater recovery of
      geniposide (59+/-1mg/g raw material). The highest values of total phenolic
      content were obtained with mesocarp extracts. The endocarp and mesocarp extracts
      presented the highest antioxidant activity as measured by FRAP and DPPH. These
      results are promising and support the use of unripe genipap fruit as a source of
      iridoids and natural antioxidants.

PMID- 29195991
TI  - Molecular identification and technological characterization of lactic acid
      bacteria isolated from fermented kidney beans flours (Phaseolus vulgaris L. and
      P. coccineus) in northwestern Argentina.
AB  - Legumes are an important protein source in developing countries and their flours
      represent an attractive alternative for the manufacture of gluten free products.
      In the present study, 4 kidney bean varieties (Alubia, Pallar, Black and Red
      beans) commonly cultivated in northwestern Argentina, were milled and
      spontaneously fermented in order to isolate and select autochthonous lactic acid
      bacteria (LAB) with relevant technological and functional properties for usage as
      starter cultures. Twelve doughs were fermented with daily back-slopping at 37
      degrees C for 6days and evolution of total mesophiles, lactic acid bacteria, and
      yeasts and molds populations were followed by plate counting. A combination of
      phenotypic and genotypic methods including (GTG)5-based PCR fingerprinting and
      16S rRNA gene sequencing were used to differentiate and identify the isolated LAB
      to species level. LAB counts ranged from around 0.89+/-0.81 to 8.74+/
      0.03logcfu/g with a pH decline from 6.4 to 3.9 throughout fermentation. Four
      genera and nine species of LAB: Enterococcus durans, E. faecium, E. mundtii, E.
      casseliflavus; Lactobacillus rhamnosus, Lactococcus garvieae, Weissella cibaria
      and W. paramesenteroides were found on kidney beans. Twenty five LAB strains were
      assessed for their abilities to grow on kidney bean extracts, acidifying
      capacities (pH and acidification rates), amylolytic, proteolytic, tannase and
      gallate decarboxylase activities as well as pathogens inhibition by
      antimicrobials. Based on these properties E. durans CRL 2178 and W.
      paramesenteroides CRL 2182 were inoculated singly and combined in Alubia kidney
      bean flour and fermented for 24h at 37 degrees C. LAB strains were beneficial for
      removing trypsin inhibitors and tannins from sourdoughs and for improving amino
      acids and phenolics contents, increasing the antioxidant activities of kidney
      bean matrices. Selected strains have potential as starter cultures for obtaining
      fermented bean products with high nutritional and functional quality.

PMID- 29195992
TI  - Phenotypic characterization of Cronobacter spp. strains isolated from foods and
      clinical specimens in Brazil.
AB  - Several Cronobacter species are opportunistic pathogens that cause infections in
      humans. This study evaluated the phenotypic characteristics of 57 Cronobacter
      strains (C. sakazakii n=41, C. malonaticus n=10, C. dublinensis n=4, and C.
      muytjensii n=2) isolated from food (n=54) and clinical specimens (n=3) in Brazil.
      These strains included sequence types (ST): ST395-ST398, ST402, ST413 and ST433
      ST439, isolated from food samples, and three C. malonaticus clinical strains
      previous isolated from an outbreak which were ST394 (n=1) and ST440 (n=2).
      Strains were tested for capsule production, biofilm formation, protease activity,
      hemolytic activity, cell-cell aggregation, and desiccation resistance. Capsule
      formation was observed with all Cronobacter strains. Forty-four (77.2%) strains
      showed proteolytic activity on milk agar. All strains showed beta-hemolysis
      against erythrocytes from guinea pig, horse and rabbit. Using erythrocytes from
      sheep, the majority of strains (53/57; 92.9%) showed alpha-hemolysis and the
      remaining, beta-hemolysis. All Cronobacter strains produced weak biofilms in
      microtiters polystyrene plates, which were independent of temperature (4, 25 and
      37 degrees C) and/or growth conditions. In glass tubes, formation of either a
      moderate or strong biofilm was observed in 15/57 (26.3%), 19/57 (33.3%) and 27/57
      (47.4%), at 4, 25 and 37 degrees C, respectively. Desiccation treatment decreased
      Cronobacter viability by 1.55 to >3.87Log10CFU/mL. Cell-cell aggregation was
      observed in 17 (29.8%) strains. This study showed that the Cronobacter species
      evaluated showed differing phenotypes, independent of their origin (clinical or
      not) and ST. Further studies are necessary to elucidate the factors affecting
      phenotype expression. This may identify novel bacterial targets that could be
      useful in the development of strategies to control Cronobacter in food chain and
      to prevent cases of infections.

PMID- 29195993
TI  - Influence of solution properties and pH on the fabrication of electrospun lentil
      flour/HPMC blend nanofibers.
AB  - Electrospinning is a method used in fiber production in which an electric force
      is applied to create jets of charged polymer solutions. The objective of this
      study was to obtain homogeneous nanofibers from lentil flour and hydroxypropyl
      methylcellulose (HPMC) blend by using electrospinning method. Distilled water was
      used as solvent. The effects of pH (7, 10 and 12), lentil flour concentration (1%
      and 2% (w/v)) and HPMC concentration (0.25%, 0.5% and 1% (w/v)) on solution
      properties and fiber morphology were investigated. When the pH was increased, the
      viscosity of the solutions containing 1% and 2% lentil flour decreased.
      Increasing the pH values caused an increase in the electrical conductivity. At pH
      value of 7, homogeneous nanofibers could not be obtained whereas fibers were
      perfectly homogeneous at alkaline pH values. Nanofiber diameter decreased with
      increase in pH when 2% lentil flour was used. On the other hand, diameter of
      fibers did not show any significant change with pH for 1% lentil flour. When the
      lentil flour concentration was increased, viscosity and fiber diameter increased
      at pH10. When HPMC concentration was increased, both viscosity and fiber diameter
      increased but electrical conductivity did not show any significant change.
      Average fiber diameters ranged between 198+/-4 and 254+/-5nm for solutions
      prepared with different lentil flour and HPMC concentrations at different pH
      values.

PMID- 29195994
TI  - Identification of variable genomic regions related to stress response in
      Oenococcus oeni.
AB  - The lactic acid bacterium Oenococcus oeni is the most important species involved
      in malolactic fermentation due to its capability to survive in presence of
      ethanol and in the acidic environment of wine. In order to identify novel genes
      involved in adaptation to wine, a new approach using genome-wide analysis based
      on stress-related genes was performed in strain O. oeni PSU-1, and 106 annotated
      stress genes were identified. The in silico analysis revealed the high similarity
      of all those genes through 57 O. oeni genomes; however, seven variable regions of
      genomic plasticity could be determined for their different presence observed
      among these strains. Regions 3 and 5 had the typical hallmarks of horizontal
      transfer, suggesting that the strategy of acquiring genes from other bacteria
      enhanced the fitness of O. oeni strains. Certain genes related to stress
      resistance were described in these regions, and similarities of putative acquired
      regions with other lactic acid bacteria species were found. Some genomic
      fragments present in all the strains were described and another new genomic
      island harbouring a threonine dehydrogenase was found. The association of
      selected sequences with adaptation to wine was assessed by screening 31 O. oeni
      strains using PCR of single genes, but no sequences were found to be exclusive to
      highly performing malolactic fermentation strains. This study provides new
      information about the genomic variability of O. oeni strains contributing to a
      further understanding of this species and the relationship of its genomic traits
      with the ability to adapt to stress conditions.

PMID- 29195995
TI  - Anchovy mince (Engraulis ringens) enriched with polyphenol-rich grape pomace
      dietary fibre: In vitro polyphenols bioaccessibility, antioxidant and physico
      chemical properties.
AB  - The aim of this study was to evaluate technological and antioxidant properties,
      including in vitro bioaccessibility of polyphenols, conferred on raw anchovy
      mince by the addition of polyphenol-rich grape pomace dietary fibre at different
      concentrations. For this purpose, headed and gutted anchovy was heat-flayed,
      deboned and mixed with 0%, 2%, 3%, 4% grape pomace dietary fibre. A significant
      increase (P<0.05) in the concentration of polyphenols and associated antioxidant
      capacity was detected when grape pomace dietary fibre was incorporated in a
      proportion of at least 2% of the final mixture. In vitro digestion showed that
      the higher the grape pomace dietary fibre content, the higher was the proportion
      of polyphenols reaching the large intestine. Additionally, it was observed that
      the ABTS (2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) assay seems to
      be more suitable for evaluating antioxidant capacity in this kind of samples than
      FRAP (Ferric Reducing Antioxidant Power) assay. Technological properties such as
      mechanical and water holding, as well as sensory scores, indicated excellent
      qualities and acceptability of all samples. Hence, given the good acceptance of
      these samples, it should be feasible to make fish products based on mince anchovy
      as a means of increasing dietary intake of polyphenols with antioxidant capacity,
      especially considering the high concentration of polyphenols bioaccessible in the
      large intestine.

PMID- 29195996
TI  - Evaluation of Tempranillo and Albarino SO2-free wines produced by different
      chemical alternatives and winemaking procedures.
AB  - In this work physical and chemical alternatives to produce SO2 free wines are
      shown. The use of inactive yeast strains enriched in glutathione, chitosan,
      dimethyldicarbonate and different hydrolysable and condensed tannins were
      assessed in Tempranillo and Albarino wines. The time of addition, mixtures of
      additives and the use of inert gases were evaluated. In general, no significant
      differences on the sensory quality were shown when compared sulphited and non
      sulphited wines. Both physical and chemical treatments were more effective for
      Tempranillo wines. In the two studied vintages, non-sulphited Tempranillo wines
      were better valuated than controls, even when wines were produced only using the
      application of inert gases. No differences were observed when argon was used
      instead of carbon dioxide as inert gas. Mixtures of seed and skin tannins with
      inactive dry yeast enriched in glutathione were the most effective treatments.
      This work may help winemakers to elaborate healthier wines meeting the current
      consumer demands.

PMID- 29195997
TI  - Instrumental and sensory properties of pea protein-fortified extruded rice
      snacks.
AB  - Characteristic attributes of pea-protein fortified, extruded rice snacks were
      evaluated by mechanical, acoustic and descriptive sensory analysis. The addition
      of pea protein isolate (0 to 45% (w/w)) to rice flour and extruder screw speed
      strongly affected the expansion behaviour and therefore, textural attributes of
      extruded snack products. The sensory panel described the texture of highly
      expanded extrudates as crisp, while low expanded extrudates were perceived as
      hard, crunchy and non-crisp. Results of the instrumental and sensory analysis
      were compared and showed a high correlation between mechanical and sensory
      hardness (r=0.98), as well as acoustic and sensory crispness (r=0.88). However,
      poor and/or negative correlations between acoustic and sensory hardness and
      crunchiness were observed (r=-0.35 and -0.84, respectively).

PMID- 29195998
TI  - Transcriptome analysis reveals the effect of pre-harvest CPPU treatment on the
      volatile compounds emitted by kiwifruit stored at room temperature.
AB  - Kiwifruits are rich in nutrients beneficial to humans. Because forchlorfenuron
      (CPPU)-treatment after full bloom can enlarge fruit size, and significantly
      increase the income of farmers, it has been extensively used. However, CPPU might
      also influence fruit sugar and acid content, and storage performance. This study
      analyzed the differences in volatile emissions between CPPU-treated and water
      treated kiwifruits after two, four, six, or eight days of storage, and
      differential gene expression related to these compounds using high-throughput
      sequencing. The number of volatile compounds was relatively high at the first two
      days of storage for both treated and control fruits, decreased in the following
      days, and increased again, although less significantly in CPPU-treated than in
      control fruits. Aldehydes in the control and treated groups showed a trend of
      stability vs. down-regulation, alcohols or terpenes showed high-low-high vs. down
      regulation, and esters showed up-regulation vs. high-low-high, respectively. Only
      60.12-66.68% of the genes obtained were mapped and 3370 new genes were annotated.
      Genes related to terpene biosynthesis were enriched, and, in CPPU-treated fruits,
      several genes related to hormone signal transduction were found in aldehydes,
      alcohols, and terpenes biosynthetic pathways. Although CPPU might influence the
      expression of genes encoding the core complex proteins in photosynthesis, its
      relationship with terpene synthesis is still unclear. Our results provided
      resources for the genetic annotation of kiwifruits, and revealed the impact of
      CPPU on the metabolism of their volatile compounds, laying the theoretical
      foundation for investigating the use of molecular techniques to inhibit the CPPU
      related reduction of fruit quality.

PMID- 29195999
TI  - The effect of raisins on biomarkers of endothelial function and oxidant damage;
      an open-label and randomized controlled intervention.
AB  - Based on the existing data in grapes and wine, the aim of the present study was
      to investigate the probability that raisins improve clinical features and markers
      of oxidative stress, inflammation and arterial function in healthy smokers.
      Thirty-six apparently healthy smokers were recruited to an open-label and
      randomized, controlled, 4-week prospective intervention. All participants were
      reported to consume less than the recommended amount of five servings fruits and
      vegetables daily. Participants in the intervention were instructed to consume
      raisins equal to five fruit servings (90g/d). Anthropometric and blood pressure
      (BP) measurements, assessment of dietary intake, and fasting blood draws were
      conducted at baseline and at week 4. Biochemical (glucose, lipids, liver
      enzymes), inflammation [C-reactive protein (CRP), leptin], oxidative stress
      [Malondialdehyde (MDA), Advanced oxidation protein products (AOPPs)] and arterial
      function markers [Flow-mediated dilatation (FMD), Pulse wave velocity (PWV),
      Intercellular adhesion molecule-1 (ICAM-1), Nitric oxide (NO)] were assessed pre-
      and post-intervention. Baseline characteristics did not differ between the
      intervention and control arm. No effect of daily raisin consumption was observed
      on markers assessed between baseline and week 4 in either arm. Regarding
      vegetable consumption, no difference was observed in either group between
      baseline and post-intervention; however, as expected, a significant increase was
      reported in the intervention arm in fruit consumption between baseline and end
      point (p<0.001) and between two arms post-intervention (p<0.001). When analyzing
      according to age, ICAM-1 levels significantly decreased in subjects >30years
      (n=8) in intervention arm (390.1+/-17.6 to 302.2+/-11ng/mL, p=0.004). After
      analysis of the data for sex, women in intervention (n=5) decreased significantly
      diastolic BP (74.6+/-4.2 to 67.4+/-2.6mg/dL, p=0.043), total cholesterol (175.8+/
      7 to 166.6+/-6.6mg/dL, p<0.001) and LDL-cholesterol (96.2+/-9.6 to 89+/
      10.5mg/dL, p=0.012). However, due to the small sample size in the above, no safe
      conclusions can be exported.

PMID- 29196000
TI  - Deep sequencing reveals high bacterial diversity and phylogenetic novelty in pit
      mud from Luzhou Laojiao cellars for Chinese strong-flavor Baijiu.
AB  - The pit mud (PM) in fermentation cellar is a complex ecosystem that hosts diverse
      microbial communities that contribute to the production of Chinese strong-flavor
      Baijiu (CSFB). However, the microbial ecology of PM, particularly the extent of
      their phylogenetic novelty remains poorly understood. Here we conducted Illumina
      MiSeq sequencing to explore the diversity and novelty patterns of PM bacterial
      communities from Luzhou Laojiao cellars in use for 40 and 400years. High
      diversity indices were found in the PM with 16 phyla and 105 genera.
      Interestingly, the compositions of dominant genera of the PM were significantly
      different than that reported previously for PM sampled from other geographic
      sites, suggesting greater microbial diversity of PM. The dominant genus of
      Caproiciproducens, a caproic acid-producing bacterium, is the first reported for
      Chinese Baijiu production. Our results demonstrate that the PM hosts a large
      number of novel taxa, with 26% of the total OTUs (operational taxonomic units)
      distant to cultured counterparts. The class Clostridia within Firmicutes
      presented the highest proportion of novel OTUs. Most novel OTUs were initially
      isolated from diverse environments, the most abundant of which came from Chinese
      Baijiu brewing ecosystems, highlighting the huge culturing gap within the PM, but
      at the same time suggesting the importance of these OTUs in CSFB production. The
      data presented in this study significantly increases the number of bacteria known
      to be associated with CSFB production and should help guide the future
      exploration of microbial resources for biotechnological applications.

PMID- 29196001
TI  - Allium tuberosum: Antidiabetic and hepatoprotective activities.
AB  - Allium tuberosum (AT) is traditionally used for treating nocturnal emissions,
      abdominal pain, diarrhea, sexual dysfunction and asthma. This study aimed at
      investigating the antidiabetic and hepatoprotective activities of the butyl
      alcohol fraction from the methanolic extract of A. tuberosum. For the
      antidiabetic activity, rats were induced with diabetes by intraperitoneal
      injection of 150mg/kg alloxan and treated for 30days with AT extract (100, 200
      and 400mg/kg). Animals were sacrificed after the study and the fasting blood
      glucose (FBG), triglyceride (TG), total cholesterol (TC), HDL, malondialdehyde
      (MDA) catalase, superoxide dismutase and glutathione levels were determined. The
      hepatoprotective assay, mice were pretreated for seven days with AT (100, 200 and
      400mg/kg) and silymarin (100mg/kg or). Thereafter 10ml/kg of 2% v/v CCl4 was
      administered intraperitoneally on the 7th day to induce acute liver injury. Blood
      and liver samples were obtained and serum enzymes ALT, AST, ALP, SOD, GSH, CAT,
      MDA and pro-inflammatory mediators were assessed. AT significantly decrease FBG,
      serum TG, TC, MDA levels and significant increased HDL, SOD, GSH and CAT
      activities in the diabetic rats. In addition, AT significantly inhibited MDA, IL
      1b, IL-6 and TNF-alpha levels and prevented the depletion of the antioxidant
      enzymes GSH, SOD and CAT activities in CCl4 induced liver damage. Furthermore, AT
      markedly reduced AST, ALT and ALP levels in the CCl4 treated mice groups. In
      conclusion, the antidiabetic and hepatoprotective effect of AT may be associated
      with its antioxidant and its ability to inhibit the pro-inflammatory mediators.

PMID- 29196002
TI  - In vitro and in vivo assessment of anti-hyperglycemic and antioxidant effects of
      Oak leaves (Quercus convallata and Quercus arizonica) infusions and fermented
      beverages.
AB  - The aim of this study was to evaluate the anti-hyperglycemic and antioxidant
      effects of oak leaves infusions and fermented beverages from Quercus convallata
      and Q. arizonica in vitro and in vivo. Female C57BL/6 mice fed with high
      saturated fat and fructose diet-induced obesity were treated with oak leaves
      beverages (200 MUL/per day equivalent to 15mg of lyophilized sample/Kg of body
      weight for infusions and 31mg of lyophilized sample/Kg of body weight for
      fermented beverages) for 3months and an oral glucose tolerance test (OGTT) was
      performed. Blood plasma was obtained for determination of glucose, lipid profile,
      and oxidative stress markers (ABTS, nitric oxide, and ORAC assays). Insulin
      resistance was estimated using the product of triglycerides and glucose (TyG).
      Oak leaves infusions and fermented beverages exhibited exerted inhibition of
      alpha-amylase (8-15% and 5-9%, respectively) and alpha-glucosidase (98% and 99%,
      respectively) enzymes. After OGTT, the groups treated with either oak leaves
      infusions or fermented beverages showed lower glucose levels compared with the
      obesity control group (18%) and a similar glucose tolerance to healthy control
      group. On long-term evaluation, intervention groups showed a significant
      reduction in fasting glucose concentrations (41-50% for oak leaves infusions and
      52-66% for fermented beverages) and TyG index (4.2-4.6% for oak leaves infusions
      and 5.9-7.5% for fermented beverages) compared with the obese control group. Oak
      leaves infusions and fermented beverages had antioxidant potential in vitro and
      scavenging activity for radicals such as peroxyl and peroxynitrite anions. Our
      results suggest anti-hyperglycemic and antioxidant effects of beverages prepared
      with leaves of Quercus species in vitro and in vivo.

PMID- 29196003
TI  - Chemical profiling of guarana seeds (Paullinia cupana) from different
      geographical origins using UPLC-QTOF-MS combined with chemometrics.
AB  - Paullinia cupana, commonly known as guarana, is an Amazonian fruit whose seeds
      are used to produce the powdered guarana, which is rich in caffeine and consumed
      for its stimulating activity. The metabolic profile of guarana from the two
      largest producing regions was investigated using UPLC-MS combined with
      multivariate statistical analysis. The principal component analysis (PCA) showed
      significant differences between samples produced in the states of Bahia and
      Amazonas. The metabolites responsible for the differentiation were identified by
      orthogonal partial least squares discriminant analysis (OPLS-DA). Fourteen
      phenolic compounds were characterized in guarana powder samples, and catechin,
      epicatechin, B-type procyanidin dimer, A-type procyanidin trimer and A-type
      procyanidin dimer were the main compounds responsible for the geographical
      variation of the samples.

PMID- 29196004
TI  - Anti-inflammatory effect of dietary pork extract on proliferation and cytokine
      secretion using mouse primary splenocytes.
AB  - The anti-inflammatory effects of boiled pork meat (BPM) and hot water extracts of
      pork meat (WPM) on splenocyte proliferation and T cell cytokine regulation in
      BALB/c mice were evaluated. The proliferation of splenocytes in high
      concentration WPM groups was significantly higher than the control stimulated by
      LPS and Con A. In the white blood cells, WPM groups had significantly higher
      counts of lymphocytes and lower counts of neutrophils than the control (p<0.05).
      The Th1 (IFN-gamma, TNF-alpha, IL-2) and Th2 (IL-4, IL-5, IL-10) cytokine levels
      in high-concentration WPM groups were higher than those in the control. In
      addition, TNF-alpha/IL-10 and IL-2/IL-4 secretions of splenocytes in the high
      concentration WPM group with LPS or Con A treatment was significantly lower than
      the control (p<0.05). Therefore, this study suggested that high concentration of
      WPM had anti-inflammatory effects on the primary splenocyte, which indicating
      that water extracts of pork meat can enhance the immune system of mice.

PMID- 29196005
TI  - Inactivation of Escherichia coli O157:H7 and Bacillus cereus by power ultrasound
      during the curing processing in brining liquid and beef.
AB  - The objective of this study was to evaluate the effects of ultrasound on the
      number of Escherichia coli O157:H7 and vegetative cells of Bacillus cereus in
      brining and beef during the curing processing. The mechanisms of the inactivation
      for the pathogens were preliminarily explored. The ultrasound intensity (2.39,
      6.23, 11.32 and 20.96Wcm-2) and sonication time (30, 60, 90 and 120min) at 10
      degrees C were assessed in brine and meat. Plate count data indicated that
      20.96Wcm-2 for 120min was the optimal treatment for bacterial reductions. E. coli
      O157:H7 was more susceptible to ultrasonic treatment in the first 30min than B.
      cereus in brine. However, a similar reduction percentage with around 40% in both
      cultures could be achieved when sonicated for 120min. Good fitness of Weibull
      model (R2>0.98; RMSE<0.12) was obtained with the distinct shape of the curves
      which predicted microbial inactivation by ultrasound in salt solution (6%). The
      production of hydrogen peroxide in brine by ultrasound confirmed the effects of
      ultrasound on the inactivation of microorganisms during the curing processing.
      The particle size distribution of bacterial and cell fluorescence staining
      analysis showed that ultrasound could result in the formation of cell fragments
      through destroying the integrality of the membrane of E. coli O157:H7 and B.
      cereus. However, the promoting effect of ultrasound on the number of bacteria in
      beef suggested that the sanitation conditions of equipment and raw meat must be
      paid attention when applying ultrasound for curing procedure.

PMID- 29196006
TI  - Understanding the influence of buckwheat bran on wheat dough baking performance:
      Mechanistic insights from molecular and material science approaches.
AB  - A molecular and material science approach is used to describe the influence of
      coarse and fine buckwheat bran on wheat dough properties and bread textural
      quality. Focus is given on (i) gluten solvation and structural arrangements in
      presence of bran as studied by front-face fluorescence; (ii) thermo-mechanical
      behavior of dough during heating studied by dynamic mechanical thermal analysis
      and (iii) texture of bread crumb analyzed in terms of a cellular solid. The
      thermo-mechanical behavior of dough was found to be largely related to starch
      phase transitions during heating. The use of thermodynamic approaches to
      biopolymer melting revealed that key transitions such as the onset of starch
      gelatinization were function of the interplay of water and bran volume fractions
      in the dough. Front-face fluorescence studies in wheat dough revealed that gluten
      solvation and structural arrangements were delayed by increasing bran addition
      level and reduction in particle size, as indicated by the drastic decrease in the
      protein surface hydrophobicity index. Variations in gluten structure could be
      strongly related to dough baking performance, i.e. specific volume. With regards
      to texture, the approach revealed that crumb texture was controlled by variations
      in density, moisture and bran volume fractions. Overall, this study elucidates a
      number of physical mechanisms describing the influence of buckwheat bran addition
      to dough and bread quality. These mechanisms strongly pointed at the influence of
      bran on water partitioning among the main polymeric components. In the future,
      these mechanisms should be investigated with bran material of varying source,
      composition and structure.

PMID- 29196007
TI  - Postharvest UV-C irradiation stimulates the non-enzymatic and enzymatic
      antioxidant system of 'Isabel' hybrid grapes (Vitis labrusca*Vitis vinifera L.).
AB  - Ultraviolet light type C (UV-C) was studied as a tool to increase enzymatic and
      non-enzymatic antioxidant defenses and phytochemical levels in 'Isabel' grapes
      (Vitis labrusca*Vitis vinifera L.). Grapes were exposed to 0, 0.5, 1.0, 2.0, or
      4.0kJm-2 UV-C and stored for 1, 3, or 5days post-treatment. One day after UV-C
      irradiation, the activities of grape antioxidant enzymes and thiols were
      increased, especially at 1.0 and 2.0kJm-2. These doses increased total phenolic
      content by almost 20%, while 0.5 and 4.0kJm-2 had no effects. Total monomeric
      anthocyanin content was increased by >35% by UV-C at 1.0kJm-2; however,
      anthocyanin profile was unchanged. Grape skin antioxidant capacity was also
      improved by UV-C irradiation. The 1.0kJm-2 UV-C was considered the hormetic dose.
      Postharvest UV-C had an elicitor effect on 'Isabel' grapes, positively impacting
      the antioxidant capacity and phytochemical content.

PMID- 29196008
TI  - Influence of buttermilk powder or buttermilk addition on phospholipid content,
      chemical and bio-chemical composition and bacterial viability in Cheddar style
      cheese.
AB  - The effect of buttermilk powder addition post-curd formation or buttermilk
      addition to cheese milk on total and individual phospholipid content, chemical
      composition, enzyme activity, microbial populations and microstructure within
      Cheddar-style cheese was investigated. Buttermilk or buttermilk powder addition
      resulted in significant increases in total phospholipid content and their
      distribution throughout the cheese matrix. Addition of 10% buttermilk powder
      resulted in higher phospholipid content, moisture, pH and salt in moisture
      levels, and lower fat, fat in dry matter, L. helveticus and non-starter bacteria
      levels in cheeses. Buttermilk powder inclusion resulted in lower pH4.6/Soluble
      Nitrogen (SN) levels and significantly lower free amino acid levels in 10%
      buttermilk powder cheeses. Buttermilk addition provided a more porous cheese
      microstructure with greater fat globule coalescence and increased free fat pools,
      while also increasing moisture and decreasing protein, fat and pH levels.
      Addition of buttermilk in liquid or powdered form offers potential for new
      cheeses with associated health benefits.

PMID- 29196009
TI  - Stability of curcumin encapsulated in solid lipid microparticles incorporated in
      cold-set emulsion filled gels of soy protein isolate and xanthan gum.
AB  - The objective of this study was to investigate the feasibility of producing cold
      set emulsion filled gels (EFG), using soy protein isolate (SPI) and xanthan gum
      (XG) and incorporating curcumin-loaded solid lipid microparticles (SLM). For this
      purpose, the formulation GXG (15%, w/v SPI, 0.1%, w/v XG and 5mM CaCl2) was
      selected for the production of EFG. A comparative study on the rheological and
      microstructural properties of non-filled gels and EFG revealed that SLM
      stabilized with Tween 80-Span 80 behaved as active fillers in the gel matrix,
      increasing the Young's modulus from 1.1 to 2.3kPa, and also increasing the values
      of storage and loss moduli. The incorporation of SLM also affected the
      microstructural organization of the systems. Whereas unfilled gels presented a
      microstructural organization similar to that of interpenetrated networks, EFG
      exhibited a microstructure with clear phase separation. The stability of
      encapsulated curcumin in EFG was monitored using a colorimetric test and it was
      confirmed that the bioactive component showed a high stability for 15days. After
      that period, the color started to change, indicating a decrease in curcumin
      concentration. The instability of curcumin was probably related to structural
      alterations of the EFG, which led to decreases of hardness after 7days of storage
      at 10 degrees C, and to the collapse of the structures after 30days. Although
      formulation improvements are required, the results indicate that the
      encapsulation of curcumin in SLM incorporated in EFG is a potential alternative
      for the replacement of yellow artificial dyes in gelled food products.

PMID- 29196010
TI  - Evaluation of the heat damage of whey and whey proteins using multivariate
      analysis.
AB  - Maillard reaction (MR) was assessed in 10 powdered whey samples. Initial stages
      of MR were evaluated using furosine, intermediate stages with
      hydroxymethylfurfural (HMF) and absorbance at 284nm, advanced stages with color
      parameters (CIELab color) and final stages with browning index; additionally,
      insolubility, pH and water activity (Aw) were measured. Principal component
      analysis (PCA) and cluster analysis (CA) were used to establish the heat damage
      of samples based on relations between variables. Three principal components were
      found which explained 79.0% of the total variance and they were the basis for
      cluster analysis where 5 clusters were formed. PCA and CA can separate samples
      according to their heat damage and they help in a clearer interpretation of the
      information from indicators which shows that samples with high lactose content
      exhibited the higher heat damage.

PMID- 29196011
TI  - Investigation of epigallocatechin-3-O-caffeoate and epigallocatechin-3-O-p
      coumaroate in tea leaves by LC/MS-MS analysis.
AB  - (-)-Epigallocatechin-3-O-gallate (EGCG), the major catechin present in green tea,
      exhibits potent antioxidant activity. We thereby investigated the presence of
      unknown components bearing the (-)-epigallocatechin (EGC) moiety in fresh tea
      leaf samples. Initially, liquid chromatography tandem mass spectrometry (LC
      MS/MS) was employed to examine fresh tea leaves of the Yabukita, the most popular
      tea cultivar in Japan, which suggested the presence of the EGC phenylpropanoid
      derivatives, (-)-epigallocatechin-3-O-p-coumaroate (EGCpCA) and (-)
      epigallocatechin-3-O-caffeoate (EGCCA). The structures of the detected EGCpCA and
      EGCCA were then confirmed by LC-MS/MS using synthesized EGCpCA and EGCCA as
      standards. In addition, EGCpCA and EGCCA were evaluated for their antioxidant
      activity in the ORAC (oxygen radical antioxidant capacity) and DPPH (2,2-diphenyl
      1-picrylhydrazyl) radical scavenging assays, where EGCCA (8.60MUmolTE/MUmol,
      TE=Trolox equivalents) exhibited a stronger antioxidant activity than EGCG
      (5.52MUmolTE/MUmol) in the ORAC assay. Finally, EGCpCA and EGCCA were quantitated
      in several tea leaf samples using LC-MS/MS, and it was found that these compounds
      were present in lower quantities (EGCpCA, 16.8-345.8MUg/g, EGCCA, 4.3-75.1MUg/g
      in the dry tea leaves) than the major catechins. In this study, we found the
      potent antioxidant EGCCA using LC-MS/MS and revealed its wide existence in
      various tea leaves.

PMID- 29196012
TI  - Repeated heat-moisture treatment exhibits superiorities in modification of
      structural, physicochemical and digestibility properties of red adzuki bean
      starch compared to continuous heat-moisture way.
AB  - The effects of repeated heat-moisture treatment (RHMT) and continuous heat
      moisture treatment (CHMT) on structural, physicochemical and digestibility
      properties of red adzuki bean starch have been investigated and compared. The
      results showed that the starch granules had many rupture and scallops and some of
      the polarization cross disappeared after CHMT and RHMT. The crystal type of CHMT
      and RHMT starches changed from C-type to A-type. The pasting temperatures and
      gelatinization transition temperatures of CHMT and RHMT starches increased, while
      the pasting viscosities (peak, trough, breakdown, final and setback viscosity),
      solubility and swelling power of CHMT and RHMT starches decreased compare to
      native starch. The RDS and SDS contents of starch samples were higher than native
      starch, which indicate that the digestibility was improved by CHMT and RHMT. On
      the whole, the RHMT measures have more advantages in the changes of starch
      structural, physicochemical and digestibility properties compared to CHMT ones.

PMID- 29196013
TI  - The potential of herbs and spices to reduce lipid oxidation during heating and
      gastrointestinal digestion of a beef product.
AB  - Here we tested the potential of ten culinary herbs (basil, oregano, rosemary and
      thyme) and spices (black pepper, cayenne pepper, cumin, curcuma, garlic and sweet
      paprika) to limit oxidation during cooking of a high-fat beef product, and during
      its subsequent in vitro gastrointestinal digestion. The herbs and spices were
      added separately at 0.5% and 1% (w/w), either during meat processing before
      heating of the product or after heating of the meat as a seasoning. Lipid
      oxidation was evaluated by malondialdehyde, 4-hydroxy-2-nonenal and hexanal
      quantification in the meat products and gastrointestinal digests. In general,
      adding the herbs and spices before heating of the meat was more effective at
      limiting oxidation during digestion, compared to adding these compounds after
      heating. Doses of 1% were more effective than 0.5%. The four herbs and curcuma
      displayed antioxidant activity in all treatments and were more effective in
      limiting oxidation than the other culinary compounds, resulting in negligible
      concentrations of 4-hydroxy-2-nonenal and hexanal in the meat and digests. Black
      pepper, cayenne pepper and cumin moderately reduced or had no effect on oxidation
      during digestion when added following heating of the meat, but had a more
      pronounced antioxidant effect when added before heating. Sweet paprika and garlic
      exerted some pro-oxidant effects during cooking. During digestion, sweet paprika
      had an antioxidant effect, but garlic did not. The extent to which the herbs and
      spices limited oxidation, showed a strong correlation with their phenolic
      content, and lower correlations with alpha-tocopherol and chlorophyll.

PMID- 29196014
TI  - Erratum to ' The immune-enhancing activity of Cervus nippon mantchuricus extract
      (NGE) in RAW264.7 macrophage cells and immunosuppressed mice' [Food Research
      International 99 (2017) start 623-629].

PMID- 29196015
TI  - Antimicrobial peptide AMPNT-6 from Bacillus subtilis inhibits biofilm formation
      by Shewanella putrefaciens and disrupts its preformed biofilms on both abiotic
      and shrimp shell surfaces.
AB  - Shewanella putrefaciens biofilm formation is of great concern for the shrimp
      industry because it adheres easily to food and food-contact surfaces and is a
      source of persistent and unseen contamination that causes shrimp spoilage and
      economic losses to the shrimp industry. Different concentrations of an
      antimicrobial lipopeptide, the fermentation product of Bacillus subtilis, AMPNT
      6, were tested for the ability to reduce adhesion and disrupt S. putrefaciens
      preformed biofilms on two different contact surfaces (shrimp shell, stainless
      steel sheet). AMPNT-6 displayed a marked dose- and time-dependent anti-adhesive
      effect>biofilm removal. 3MIC AMPNT-6 was able both to remove biofilm and prevent
      bacteria from forming biofilm in a 96-well polystyrene microplate used as the
      model surface. 2MIC AMPNT-6 prevented bacteria from adhering to the microplate
      surface to form biofilm for 3h and removed already existing biofilm within 24h.
      Secretion of extracellular polymeric substances incubated in LB broth for 24h by
      S. putrefaciens was minimal at 3* MIC AMPNT-6. Scanning electron microscopy
      showed that damage to S. putrefaciens bacteria by AMPNT-6 possibly contributed to
      the non-adherence to the surfaces. Disruption of the mature biofilm structure by
      AMPNT-6 contributed to biofilm removal. It is concluded that AMPNT-6 can be used
      effectively to prevent attachment and also detach S. putrefaciens biofilms from
      shrimp shells, stainless steel sheets and polystyrene surfaces.

PMID- 29196016
TI  - Evaluation of bioactive compounds potential and antioxidant activity in some
      Brazilian exotic fruit residues.
AB  - The agroindustrial residues have been recognized as important sources of some
      prominent chemical compounds and hence a viable strategy of obtaining bioactive
      compounds could be applied to them. The present study was aimed to investigate
      the presence of bioactive compounds and the antioxidant activity of some
      Brazilian exotic fruits (achachairu, araca-boi, bacaba) residues. The antioxidant
      capacity of fruit residues was evaluated by ORAC, FRAP and ABTS assays. The
      contents of total phenolic compounds, flavonoids, chlorophylls and carotenoids
      were determined. The identification and quantification of the phenolic compounds
      were performed by using the UHPLC-QqQ-MS/MS system. The compounds cinnamic acid,
      p-coumaric acid, epicatechin and quercetin were identified and quantified in all
      fruits residues. The residue with the highest antioxidant capacity was bacaba for
      ORAC (15,285.51+/-20.38MUmolTE/100g) and FRAP (16,916.37+/-10.01MUmolTE/100g)
      assays, as well as total phenolic compounds in its methanolic extract (1537.45+/
      73.35mgGAE/100g).

PMID- 29196017
TI  - Traditional fermentation of tef injera: Impact on in vitro iron and zinc
      dialysability.
AB  - Tef [Eragrostis tef (Zucc.) Trotter], an ancient cereal mainly produced in
      Ethiopia, is increasingly getting higher acceptance in the global market because
      it is gluten free and has high iron content. The aim of this study was to
      evaluate the in vitro dialysability of Fe and Zn in a backslop fermented gluten
      free flat bread known as injera. The traditional fermentation caused up to 49-66%
      reduction of phytic acid (PA). Molar ratios of PA:Fe and PA:Zn decreased from 14
      to 1 and from 63 to 19, respectively, after 120h of fermentation. The total
      soluble fractions of Fe and Zn ranged between 11 and 38% and between 11 and 29%,
      respectively, after 120h of fermentation. The dialyzable Fe content of the white
      varieties ranged between 3 and 9% after 120h fermentation while no effect was
      observed for the brown varieties. The dialyzable Zn ranged between 2 and 11%,
      with only a clear effect of fermentation in one white variety. Consumption of tef
      could be a good source of Fe and Zn, but may not provide the absolute recommended
      daily Fe and Zn intakes.

PMID- 29196019
TI  - Modeling take-over performance in level 3 conditionally automated vehicles.
AB  - Taking over vehicle control from a Level 3 conditionally automated vehicle can be
      a demanding task for a driver. The take-over determines the controllability of
      automated vehicle functions and thereby also traffic safety. This paper presents
      models predicting the main take-over performance variables take-over time,
      minimum time-to-collision, brake application and crash probability. These
      variables are considered in relation to the situational and driver-related
      factors time-budget, traffic density, non-driving-related task, repetition, the
      current lane and driver's age. Regression models were developed using 753 take
      over situations recorded in a series of driving simulator experiments. The models
      were validated with data from five other driving simulator experiments of mostly
      unrelated authors with another 729 take-over situations. The models accurately
      captured take-over time, time-to-collision and crash probability, and moderately
      predicted the brake application. Especially the time-budget, traffic density and
      the repetition strongly influenced the take-over performance, while the non
      driving-related tasks, the lane and drivers' age explained a minor portion of the
      variance in the take-over performances.

PMID- 29196018
TI  - Differentiating the influence of incidental anger and fear on risk decision
      making.
AB  - Previous research has revealed that incidental emotions of different valence
      (positive/negative/neutral) produce distinct impacts on risk decision-making.
      This study went on to compare the effects of different emotions of which the
      valence are identical. We focused on anger and fear, both of which are negative
      emotions but differ in motivational and appraisal dimensions. Participants
      finished a forced-choice gambling task, during which incidental emotions
      (anger/fear/happy) were elicited by facial stimuli selected from the Chinese
      Facial Affective Picture System. Behavioral and event-related potential (ERP)
      data were recorded in the experiment, which showed that anger and fear were
      different in their influence on behavioral risk preference and the relationship
      between outcome processing and subsequent risk decisions. Regarding the
      behavioral results, risk preference in the anger condition was higher than the
      fear condition, but lower than the happy condition. Regarding the ERP results
      elicited by outcome feedback (gain/loss), in the fear condition, the feedback
      related negativity (FRN) was positively correlated with risk preference; in the
      anger condition, the gain-related P3 component was positively correlated with
      risk preference; in the happy condition, both the FRN and the loss-related P3 was
      negatively correlated with risk preference. The current findings provide novel
      insight into distinguishing the effect of different incidental emotions on risk
      preference.

PMID- 29196020
TI  - Evaluation of Multifocality and Multicentricity With Breast Magnetic Resonance
      Imaging in Each Breast Cancer Subtype.
AB  - INTRODUCTION: The purpose of this study was to evaluate whether diagnostic
      performance of breast magnetic resonance imaging (MRI) for detection of
      multifocality and multicentricity (MFMC) of breast cancer (BC) can be influenced
      by different histotypes or immunophenotypes in newly diagnosed patients with
      breast cancer. MATERIALS AND METHODS: In this institutional review board-approved
      retrospective study, 289 patients who underwent both preoperative breast MRI and
      radical or modified mastectomy in our institution because of primary BCs were
      selected. Patients were stratified based on the pathologic report in 2 main
      histotypes and 5 immunophenotypes. By matching the radiologic report with the
      corresponding pathologic report for each patient, breast MRI performance for
      detection of MFMC were obtained in each histotype and immunophenotype and
      subsequently compared. RESULTS: Overall breast MRI sensitivity for MFMC detection
      was 88.1%, specificity was 80.0%, positive predictive value 82.1%, negative
      predictive value 85.8%, diagnostic accuracy 83.7%, and area under the curve
      0.835. Breast MRI sensitivity for MFMC detection in triple-negative BC was 84.6%
      (P = .88), specificity 70.8% (P = .63), positive predictive value 61.1% (P =
      .02), negative predictive value 89.5% (P = .20), diagnostic accuracy 75.7% (P =
      .65), and area under the curve 0.777 (P = .87). CONCLUSION: Performance of breast
      MRI for the detection of MFMC are not influenced by the BC histotypes, in
      accordance with published literature. Conversely, the triple-negative
      immunophenotypes demonstrated lower performance, statistically significant only
      for positive predictive value (P = .02), for the detection of MFMC.

PMID- 29196021
TI  - Advanced imaging to predict response to chemotherapy in colorectal liver
      metastases - a systematic review.
AB  - BACKGROUND: The assessment of colorectal liver metastases (CRLM) after treatment
      with chemotherapy is challenging due to morphological and/or functional change
      without changes in size. The aim of this review was to assess the value of FDG
      PET, FDG-PET-CT, CT and MRI in predicting response to chemotherapy in CRLM.
      METHODS: A systematic review was undertaken based on PRISMA statement. PubMed and
      Embase were searched up to October 2016 for studies on the accuracy of PET, PET
      CT, CT and MRI in predicting RECIST or metabolic response to chemotherapy and/or
      survival in patients with CRLM. Articles evaluating the assessment of response
      after chemotherapy were excluded. RESULTS: Sixteen studies met the inclusion
      criteria and were included for further analysis. Study results were available for
      6 studies for FDG-PET(-CT), 6 studies for CT and 9 studies for MRI. Generally,
      features predicting RECIST or metabolic response often predicted shorter
      survival. The ADC (apparent diffusion coefficient, on MRI) seems to be the most
      promising predictor of response and survival. In CT-related studies, few
      attenuation-related parameters and texture features show promising results. In
      FDG-PET(-CT), findings were ambiguous. CONCLUSION: Radiological data on the
      prediction of response to chemotherapy for CRLM is relatively sparse and
      heterogeneous. Despite that, a promising parameter might be ADC. Second, there
      seems to be a seemingly counterintuitive correlation between parameters that
      predict a good response and also predict poor survival.

PMID- 29196022
TI  - A Systematic review and meta-analysis on the role of palliative primary resection
      for pancreatic neuroendocrine neoplasm with liver metastases.
AB  - BACKGROUND: Role of palliative pancreatic neuroendocrine neoplasm (PanNEN)
      resection (pPanNEN-R) is controversial. This study was designed as a meta
      analysis of studies which allow a comparison of pPanNEN-R and non-surgical
      management (PanNEN-nR). METHODS: All published studies until 2017 allowing for
      the comparison of pPanNEN-R and PanNEN-nR were reviewed. Primary outcome was
      overall survival (OS). Secondary outcomes measures included postoperative
      morbidity, reoperation, readmission, length of hospital stay (LOS), and quality
      of life (QoL). Risk of death was compared by computing the odds-ratio (OR), while
      5- and 10-year OS using weighted mean differences. RESULTS: Seven studies were
      included. A total of 885 patients were included, of whom 252 (28%) underwent
      pPanNEN-R and 633 (72%) underwent PanNEN-nR. Overall quality of included studies
      was fair. The risk of death was significantly reduced in patients who underwent
      pPanNEN-R compared to those who underwent PanNEN-nR (OR = 0.38, 95% CI 0.23
      0.65). Data on postoperative morbidity, reoperation, readmission, LOS, and QoL
      were not adequately reported therefore a meta-analysis for the secondary outcomes
      was not performed. DISCUSSION: pPanNEN-R in patients with unresectable LM seems
      to be associated with a better OS compared to non-surgical management but the
      limitations of included studies does not allow firm conclusions.

PMID- 29196023
TI  - Zataria multiflora would attenuate the hepatotoxicity of long-term albendazole
      treatment in mice with cystic echinococcosis.
AB  - Hepatic injury is the major limitation of long-term albendazole administration in
      patients with cystic echinococcosis (CE), which could give rise to cessation of
      treatment. The objective of the present study was to evaluate the protective
      effects of Zataria multiflora aromatic water (AW) against the hepatic injury
      induced by long-term albendazole treatment in mice with CE. Fifty healthy BALB/c
      female mice were infected intraperitoneally by injection of 1500 protoscoleces
      per animal. Five months after infection, the infected animals were divided into
      five treatment groups including Z. multiflora (40ml/l in drinking water for
      90days), albendazole (200mg/kg/day for 90days), Z. multiflora+albendazole 200
      (40ml/l Z. multiflora and 200mg/kg/day albendazole for 90days), Z.
      multiflora+albendazole100 (40ml/l Z. multiflora and 100mg/kg/day albendazole for
      90days), and untreated (control) group. At the end of the treatment period,
      anesthesia was performed and blood samples were collected directly from the heart
      prior to euthanasia. Liver variables and oxidative stress markers were measured
      in the blood serum samples. A decrease in serum liver enzyme activity in the both
      Z. multiflora+albendazole groups was observed when compared to control, Z.
      multiflora and albendazole groups; however, the results for Z.
      multiflora+albendazole 100 were significant (p<0.007) and superior compared to
      those for Z. multiflora+albendazole 200. No significant differences for oxidative
      stress markers were observed between the different groups. The results of the
      present study revealed that a combined therapy with Z. multiflora AW and
      albendazole is effective against hepatic injury induced by CE and/or long term
      albendazole administration in mice with cystic echinococcosis.

PMID- 29196024
TI  - Poly(methyl vinyl ether-co-maleic acid) for enhancement of solubility, oral
      bioavailability and anti-osteoporotic effects of raloxifene hydrochloride.
AB  - Raloxifene HCl (RH) has poor water solubility and due to its extensive first pass
      metabolism; its bioavailability is only 2%. The purpose of the present study was
      to enhance the aqueous solubility, oral bioavailability and anti-osteoporotic
      effects of RH by electro-sprayed nanoparticles (NPs) in ovariectomized rats. NPs
      containing RH and different ratio of poly(methyl vinyl ether-co-maleic acid)
      (PMVEMA) were electrosprayed. The voltage, distance of needle to the collector,
      flow rate of the solution and polymeric percentage were optimized according to
      the size of NPs and drug solubility. The optimized formulation was characterized
      by SEM, XRD, DSC, and FTIR. The pharmacokinetic parameters were studies by oral
      administration of a single dose of 15mg/kg in Wistar rats. The anti-osteoporotic
      effects were studied in female ovariectomized rats. Animals were treated with
      6mg/kg/day for 2months then serum calcium, phosphorous and alkaline phosphatase
      levels were measured. RH loaded electrosprayed NPs showed 10-fold enhanced
      solubility compared to the free drug. Moreover, the XRD and SEM tests displayed
      an amorphous state of drug in the NPs. FTIR and DSC tests revealed no interaction
      between the polymer and the drug. Serum calcium, phosphorous and alkaline
      phosphatase levels were significantly decreased in ovariectomized rats receiving
      oral RH NPs (P<0.05). No significant difference was detected between RH NPs and
      estradiol groups (P>0.05). Oral bioavailability of NPs showed 7.5-fold increase
      compared to the pure drug. The electrosprayed PMVEMA nanoparticles can enhance
      solubility, bioavailability and antiosteoporotic effects of RH.

PMID- 29196025
TI  - Pharmacological variability of insulins degludec and glargine 300U/mL: Equivalent
      or not?

PMID- 29196026
TI  - Long-term Changes in the Nigrostriatal Pathway in the MPTP Mouse Model of
      Parkinson's Disease.
AB  - Parkinson's disease (PD) is a common and progressive neurodegenerative disorder.
      The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD is
      widely used to study the progression of this disease. Behavior impairment is
      closely related to the damage of the dopaminergic system in the basal ganglia.
      Here, MPTP-induced changes in mouse behavior and glial activation were evaluated
      at different time points after the treatment and the long-term changes in the
      nigrostriatal pathway were analyzed. We found that mice exposed to MPTP displayed
      a full recovery in the rotarod test and the pole test but not in the wire hanging
      test at 65 days post-injection. A biphasic activation of microglial cells was
      revealed in the nigrostriatal pathway of MPTP-treated mice. However, activation
      of astrocytes displayed an approximately bell-shaped kinetics and an
      approximately S-shaped kinetics in the striatum and the substantia nigra,
      respectively. In addition, the numbers of complement component 3 (C3)-positive
      neurotoxic astrocytes in the substantia nigra of MPTP-treated mice increased with
      time and reached a maximum at 42 days, and declined at 74 days, after the
      treatment. Three months later, the dopaminergic system was partially recovered
      from the lesion of MPTP. The time course of pathophysiological events has
      important implications for the interventions or treatment of PD.

PMID- 29196027
TI  - Cancer Chemotherapy in Early Life Significantly Alters the Maturation of Pain
      Processing.
AB  - Advances in pediatric cancer treatment have led to a ten year survival rate
      greater than 75%. Platinum-based chemotherapies (e.g. cisplatin) induce
      peripheral sensory neuropathy in adult and pediatric cancer patients. The period
      from birth through to adulthood represents a period of maturation within
      nociceptive systems. Here we investigated how cisplatin impacts upon postnatal
      maturation of nociceptive systems. Neonatal Wistar rats (Postnatal day (P) 7)
      were injected (i.p.) daily with either vehicle (PBS) or cisplatin (1mg/kg) for
      five consecutive days. Neither group developed mechanical or thermal
      hypersensitivity immediately during or after treatment. At P22 the cisplatin
      group developed mechanical (P < 0.05) and thermal (P < 0.0001) hypersensitivity
      versus vehicle group. Total DRG or dorsal horn neuronal number did not differ at
      P45, however there was an increase in intraepidermal nerve fiber density in
      cisplatin-treated animals at this age. The percentage of IB4+ve, CGRP+ve and
      NF200+ve DRG neurons was not different between groups at P45. There was an
      increase in TrkA+ve DRG neurons in the cisplatin group at P45, in addition to
      increased TrkA, NF200 and vGLUT2 immunoreactivity in the lumbar dorsal horn
      versus controls. These data highlight the impact pediatric cancer chemotherapy
      has upon the maturation of pain pathways and later life pain experience.

PMID- 29196028
TI  - Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of
      Beclin 1-Dependent Autophagy.
AB  - Serum response factor (SRF), a transcription factor highly expressed in neurons,
      is involved in neuronal survival and the pathogenesis of some neurodegenerative
      disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons
      vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity,
      however, the underlying mechanisms remain poorly understood. Here, we report
      decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that
      was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF
      expression was also reduced in rotenone-treated PC12 cells in vitro. In addition,
      Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast,
      overexpression of Srf attenuated the cells' sensitivity to rotenone and
      alleviated rotenone-induced alpha-synuclein accumulation. The protective effect
      of SRF was abolished when the expression of autophagy-related proteins Beclin 1
      and Atg5 was suppressed. These results suggested that SRF may promote DA neuron
      survival by regulating autophagy, and thus serves as a critical molecule in PD
      progression.

PMID- 29196029
TI  - Assessment of phototoxicity in pigmented Long-Evans rat: sparfloxacin and 8
      methoxypsoralen.
AB  - The aim of the present work was to evaluate the effects of photo-activated
      toxicity induced after administration of two known melanin-binding phototoxic
      compounds, sparfloxacin (SPX) and 8-methoxypsoralen (8-MOP), followed or not by
      UVA/Vis exposure, in pigmented rats (Long Evans: LE) and albino rats (Sprague
      Dawley: SD). Groups of three rats were treated with SPX or 8-MOP by oral gavage
      for six consecutive days. Irradiated animals were submitted to a UVA/Vis light
      dose standardized to 10 J/cm2 UVA daily. Clinical signs, cutaneous reactions and
      body weight were monitored throughout the study period. Ear biopsy weight, lymph
      node weight and lymph node cell count were determined at necropsy. Ophthalmologic
      examinations were performed before the first treatment and on the day of
      sacrifice. Microscopic examinations were performed on skin biopsies and eyes.
      Phototoxicity was demonstrated for both SPX and 8-MOP in the pigmented and albino
      strains, in terms of auricular irritation, lymph node weight and proliferation
      index, cutaneous reactions and ocular histopathology. LE rats were less sensitive
      than SD rats, especially at the ocular level, supporting the notion that
      pigmentation may provide protection against photo-activation. The pigmented rat
      may be a more relevant model than the albino rat for human safety evaluation.

PMID- 29196030
TI  - Expert opinions on the acceptance of alternative methods in food safety
      evaluations: Formulating recommendations to increase acceptance of non-animal
      methods for kinetics.
AB  - Inclusion of alternative methods that replace, reduce, or refine (3R) animal
      testing within regulatory safety evaluations of chemicals generally faces many
      hurdles. The goal of the current work is to i) collect responses from key
      stakeholders involved in food safety evaluations on what they consider the most
      relevant factors that influence the acceptance and use of 3R methods and to ii)
      use these responses to formulate activities needed to increase the acceptance and
      use of 3R methods, particularly for kinetics. The stakeholders were contacted by
      e-mail for their opinions, asking the respondents to write down three barriers
      and/or drivers and scoring these by distributing 5 points over the three factors.
      The main barriers that obtained the highest aggregated scores were i) uncertain
      predictability 3R methods/lack of validation, ii) insufficient guidance
      regulators/industry and iii) insufficient harmonization of legislation. The major
      driver identified was the possibility of 3R methods to provide more mechanistic
      information. Based on the results, recommendations are given to enhance the
      acceptance and application of 3R toxicokinetic methods in food safety
      evaluations. These include steering of regulatory data requirements as well as
      creating (funding) opportunities for development and validation of alternative
      methods for kinetics and development of guidances.

PMID- 29196031
TI  - Effects of various feeding patterns of Bacillus coagulans on growth performance,
      antioxidant response and Nrf2-Keap1 signaling pathway in juvenile gibel carp
      (Carassius auratus gibelio).
AB  - The present study was conducted to evaluate the effects of various Bacillus
      coagulans feeding patterns on growth, antioxidant parameter and Nrf2 pathway in
      juvenile gibel carp. The similar size of gibel carp (initial weight: 14.33 +/-
      0.15 g) were subjected to three levels of B. coagulans supplementation (0, 500,
      and 1000 mg/kg) and two feeding modes (supplementing B. coagulans continuously or
      for two days of B. coagulans after 5 days of a basal diet) according to a 3 * 2
      factorial design. The fish that were continuously fed 500 mg/kg B. coagulans (P2)
      and those fed the first basal diet for 5 days followed by 500 mg/kg or 1000 mg/kg
      B.coagulans for 2 days (P4 or P5) showed higher weight gain rate and specific
      growth rate than the other groups. Blood respiratory burst (RB), myeloperoxidase
      (MPO), and anti-superoxide anion free radical (AFASER) activities in the P4 group
      were higher than those of the control. White blood cell count (WBC), RB activity,
      MPO activity, and glutathione (GSH) content in the P5 group were also higher than
      those of the control. A similar higher trend was observed in the gene expressions
      of NADPH oxidase 2 (NOX2), NFE2-related factor (Nrf2), Kelch-like-ECH-associated
      protein(Keap1) in the P4 and NOX2, NRF2, CNC homolog 1 (Bach1), peroxiredoxin 2
      (Prx2) in the P5 group compared with the control. Additionally, we observed a
      significantly lower level of plasma aspartate aminotransferase (AST), lower
      activity of alanine aminotransferase (ALT), a higher level of MPO, higher GPX
      activity, and increased NRF2 and Prx2 expression were all observed in the P2
      treatment group compared with the control. Furthermore, the malondialdehyde (MDA)
      content in the P2, P3, and P4 groups was lower than that of the control. These
      results indicate that a diet supplemented with appropriate levels of B.coagulans
      could improve the growth, immune response, and antioxidant capability of gibel
      carp. We concluded that the pattern of two days of 500 or 1000 mg/kg B. coagulans
      after 5 days of a basal diet was recommended for gibel carp.

PMID- 29196033
TI  - Sedation with midazolam without neurotoxic effects.

PMID- 29196032
TI  - Current methods and limitations for longitudinal fMRI analysis across
      development.
AB  - The human brain is remarkably plastic. The brain changes dramatically across
      development, with ongoing functional development continuing well into the third
      decade of life and substantial changes occurring again in older age. Dynamic
      changes in brain function are thought to underlie the innumerable changes in
      cognition, emotion, and behavior that occur across development. The brain also
      changes in response to experience, which raises important questions about how the
      environment influences the developing brain. Longitudinal functional magnetic
      resonance imaging (fMRI) studies are an essential means of understanding these
      developmental changes and their cognitive, emotional, and behavioral correlates.
      This paper provides an overview of common statistical models of longitudinal
      change applicable to developmental cognitive neuroscience, and a review of the
      functionality provided by major software packages for longitudinal fMRI analysis.
      We demonstrate that there are important developmental questions that cannot be
      answered using available software. We propose alternative approaches for
      addressing problems that are commonly faced in modeling developmental change with
      fMRI data.

PMID- 29196034
TI  - Adie pupil. Pilocarpine test.

PMID- 29196035
TI  - Is it time to discuss on low-intervention clinical trials without participants'
      informed consent?

PMID- 29196037
TI  - Analysis of severe cases of epidemic influenza and its lethality in the last 5
      flu seasons.

PMID- 29196036
TI  - Severe myopericarditis following induction therapy with idarubicin and
      transretinoic acid in a patient with acute promyelocytic leukemia.

PMID- 29196038
TI  - Diabetic ketoacidosis by empaglifozin and intestinal obstruction. The importance
      of arterial blood gas analysis.

PMID- 29196039
TI  - Alzheimer's disease: An ignored condition.

PMID- 29196040
TI  - Non-oncological applications of PET/CT.

PMID- 29196041
TI  - Nose-to-brain delivery of insulin enhanced by a nanogel carrier.
AB  - Recent evidences suggest that insulin delivery to the brain can be an important
      pharmacological therapy for some neurodegenerative pathologies, including
      Alzheimer disease (AD). Due to the presence of the Blood Brain Barrier, a
      suitable carrier and an appropriate route of administration are required to
      increase the efficacy and safety of the treatment. Here, poly(N-vinyl
      pyrrolidone)-based nanogels (NG), synthetized by e-beam irradiation, alone and
      with covalently attached insulin (NG-In) were characterized for biocompatibility
      and brain delivery features in a mouse model. Preliminarily, the biodistribution
      of the "empty" nanocarrier after intraperitoneal (i.p.) injection was
      investigated by using a fluorescent-labeled NG. By fluorescence spectroscopy, SEM
      and dynamic light scattering analyses we established that urine clearance occurs
      in 24h. Histological liver and kidneys inspections indicated that no
      morphological alterations of tissues occurred and no immunological response was
      activated after NG injection. Furthermore, after administration of the insulin
      conjugated nanogels (NG-In) through the intranasal route (i.n.) no alteration or
      immunogenic response of the nasal mucosa was observed, suggesting that the
      formulation is well tolerated in mouse. Moreover, an enhancement of NG-In
      delivery to the different brain areas and of its biological activity, measured as
      Akt activation levels, with reference to free insulin administration was
      demonstrated. Taken together, these results indicate that the synthesized NG-In
      enhances brain insulin delivery upon i.n. administration and strongly encourage
      its further evaluation as therapeutic agent against some neurodegenerative
      diseases.

PMID- 29196042
TI  - Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute
      spinal cord injury.
AB  - As one of the most devastating forms of trauma, spinal cord injury (SCI) remains
      a challenging clinical problem. The secondary processes associated with the
      primary injury, such as overproduction of reactive oxygen species (ROS) and
      inflammation, lead to concomitant compression of the injured spinal cord and
      neuronal death. Delivery of copper-zinc superoxide dismutase (SOD1), an efficient
      ROS scavenger, to the site of injury can mitigate SCI-induced oxidative stress
      and tissue damage. Towards this goal catalytically active nanoformulations of
      SOD1 ("nanozymes") are developed as a modality for treatment of SCI. Along with
      the cross-linked polyion complex of SOD1 with polycation poly(ethylene glycol)
      (PEG)-polylysine (single-coat (SC) nanozyme), we introduce for the first time the
      chemically cross-linked multilayer polyion complex in which SOD1 is first
      incorporated into a polyion complex with polycation, then coated by anionic block
      copolymer, PEG-polyglutamic acid (double-coat (DC) nanozyme). We developed DC
      nanozymes with high enzymatic activity and ability to retain and protect SOD1
      under physiological conditions. Pharmacokinetic study revealed that DC nanozymes
      significantly prolonged circulation of active SOD1 in the blood stream compared
      to free SOD1 or SC nanozymes (half-life was 60 vs 6min). Single intravenous
      injection of DC nanozymes (5kU of SOD1/kg) improved the recovery of locomotor
      functions in rats with moderate SCI, along with reduction of swelling,
      concomitant compression of the spinal cord and formation of post-traumatic cysts.
      Thus, based on the testing in a rodent model the SOD1 DC nanozymes are promising
      modality for scavenging ROS, decreasing inflammation and edema, and improving
      recovery after SCI.

PMID- 29196044
TI  - Epithelia transmembrane transport of orally administered ultrafine drug particles
      evidenced by environment sensitive fluorophores in cellular and animal studies.
AB  - Little is known about the in vivo fate of drug particles taken orally, in
      particular, the drug release kinetics and interaction with the gastrointestinal
      (GI) membrane. Lacking is analytical means that can reliably identify the
      integrity of drug particles under the complexity of biological environment.
      Herein, we explored fluorescent probes whose signals become quenched upon being
      released from drug carriers. Taking advantage of so-called the aggregation caused
      quenching (ACQ), particles may be identified by the integrated fluorophores,
      which are "turned off" when the particles become destructed and dyes are
      released. In the current study, ultrafine amorphous particles (UAPs) of
      cyclosporin A (CsA) were prepared with synthesized ACQ dyes physically entrapped.
      The fluorescence intensity of suspension of these UAPs was found correlated well
      with the dissolution of the particles. When given to rats orally, it was found
      that some of the administered UAPs could survive the animal's GI tracts for as
      long as 18h. Whole-body fluorescence imaging detected fluorescent signals in the
      liver and lungs. Particularly noticed in sections of jejunum and ileum, the
      detection suggested the possibility of direct absorption of UAPs through
      epithelial membranes. Moreover, 250nm particles were absorbed faster via
      transepithelia than larger ones (550nm), while the latter were preferably taken
      up by M cells in the follicle-associated epithelium (FAE) region of Peyer's
      patches. In vitro permeation studies with Caco-2 cells confirmed the
      transmembrane transport of the dye-integrated UAPs. Our study supports the idea
      of using ACQ fluorophores for imaging and characterizing the fate of intact
      particles in a biological environment.

PMID- 29196045
TI  - Cystic fibrosis: a call for papers for ECFS 2018.

PMID- 29196043
TI  - Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38
      targeted nanoparticles in multiple myeloma.
AB  - The establishment of more effective treatments that can circumvent
      chemoresistance in Multiple Myeloma (MM) is a priority. Although bortezomib (BTZ)
      is one of the most potent proteasome inhibitors available, still possesses
      limitations related to dose limiting side effects. Several strategies have been
      developed to improve the delivery of chemotherapies to MM by targeting different
      moieties expressed on MM cells to nanoparticle delivery systems (NPs), which have
      failed mainly due to their heterogeneous expression on these cells. Our goal was
      to test CD38 targeted chitosan NPs as novel targeting moiety for MM to improve
      the potency and efficacy of BTZ in MM cells and reduce the side effects in
      healthy tissue. We have showed preferential BTZ release in tumor
      microenvironment, specific binding to MM cells, and an improved drug cellular
      uptake through BTZ diffusion from the surface and endocytosed NPs, which
      translated in enhanced proteasome inhibition and robust cytotoxic effect on MM
      cells when BTZ was administered through anti-CD38 chitosan NPs. Furthermore, the
      anti-CD38 chitosan NPs specifically delivered therapeutic agents to MM cells
      improving therapeutic efficacy and reducing side effects in vivo. The anti-CD38
      chitosan NPs showed low toxicity profile allowing enhancement of proteasome
      inhibitory activity and specificity of BTZ by endocytosis-mediated uptake of CD38
      representing a promising therapy in MM.

PMID- 29196047
TI  - Antibiotic administration in the ambulance?

PMID- 29196049
TI  - Chronic glucocorticoid treatment induced circadian clock disorder leads to lipid
      metabolism and gut microbiota alterations in rats.
AB  - AIM: Glucocorticoids (GCs), steroid hormones synthetized by the adrenal gland,
      are regulated by circadian cycles, and dysregulation of GC signaling can lead to
      the development of metabolic syndrome. The effects and potential mechanism of GCs
      in physiology were investigated in the present study. MAIN METHODS: Male Wistar
      rats were orally administered dexamethasone sodium phosphate (DEX, 0.01 and
      0.05mg/kg body weight per day) for 7weeks. KEY FINDING: DEX treatment attenuated
      body weight gain and reduced food intake, whereas it induced the accumulation of
      fat. Administration of DEX induced dysregulation of the expression of lipogenic
      genes in both fat and liver. Moreover, the mRNA levels of genes related to
      mitochondrial biogenesis and function were significantly downregulated in the
      liver and fat of DEX-treated rats. Furthermore, DEX treatment caused a
      significant reduction in the richness and diversity of the microbiota in the
      colon, as assessed using high-throughput sequencing of the 16s rRNA gene V3-V4
      region, an increase in inflammatory cell infiltration, and a decrease in mucus
      secretion in the colon. Additionally, DEX administration induced phase shift or
      loss of circadian rhythmicity of clock-related genes in peripheral tissues. These
      results were associated with higher serum corticosterone levels and upregulation
      of GC receptor (GR) expression in peripheral tissues. SIGNIFICANCE: Our findings
      indicate that long-term administration of GC caused lipid accumulation, changes
      in the structure of the intestinal flora, and reduced colonic mucus secretion in
      vivo. The mechanism of these physiological changes may involve a circadian rhythm
      disorder and dysregulation of GR expression.

PMID- 29196046
TI  - Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label,
      randomised trial.
AB  - BACKGROUND: Emergency medical services (EMS) personnel have already made
      substantial contributions to improving care for patients with time-dependent
      illnesses, such as trauma and myocardial infarction. Patients with sepsis could
      also benefit from timely prehospital care. METHODS: After training EMS personnel
      in recognising sepsis, we did a randomised controlled open-label trial in ten
      large regional ambulance services serving 34 secondary and tertiary care
      hospitals in the Netherlands. We compared the effects of early administration of
      antibiotics in the ambulance with usual care. Eligible patients were randomly
      assigned (1:1) using block-randomisation with blocks of size 4 to the
      intervention (open-label intravenous ceftriaxone 2000 mg in addition to usual
      care) or usual care (fluid resuscitation and supplementary oxygen). Randomisation
      was stratified per region. The primary outcome was all-cause mortality at 28 days
      and analysis was by intention to treat. To assess the effect of training, we
      determined the average time to antibiotics (TTA) in the emergency department and
      recognition of sepsis by EMS personnel before and after training. The trial is
      registered at ClinicalTrials.gov, number NCT01988428. FINDINGS: 2698 patients
      were enrolled between June 30, 2014, and June 26, 2016. 2672 patients were
      included in the intention-to-treat analysis: 1535 in the intervention group and
      1137 in the usual care group. The intervention group received antibiotics a
      median of 26 min (IQR 19-34) before arriving at the emergency department. In the
      usual care group, median TTA after arriving at the emergency department was 70
      min (IQR 36-128), compared with 93 min (IQR 39-140) before EMS personnel training
      (p=0.142). At day 28, 120 (8%) patients had died in the intervention group and 93
      (8%) had died in the usual care group (relative risk 0.95, 95% CI 0.74-1.24). 102
      (7%) patients in the intervention group and 119 (10%) in the usual care group
      were re-admitted to hospital within 28 days (p=0.0004). Seven mild allergic
      reactions occurred, none of which could be attributed to ceftriaxone.
      INTERPRETATION: In patients with varying severity of sepsis, EMS personnel
      training improved early recognition and care in the whole acute care chain.
      However, giving antibiotics in the ambulance did not lead to improved survival,
      regardless of illness severity. FUNDING: The NutsOhra Foundation, Netherlands
      Society of Internal Medicine (NIV).

PMID- 29196048
TI  - Developmental competence and apoptotic gene expression patterns of mature and
      immature human oocytes retrieved from controlled ovarian stimulation cycles.
AB  - The purpose was to assess the developmental competence of the in vitro or in vivo
      matured human oocytes as well as the apoptotic genes expression of cumulus cells
      (CCs) regarding nuclear maturity status of associated oocytes retrieved from
      stimulated ICSI cycles. A total of 590 oocytes and the associated CCs were
      retrieved and divided into groups of test and control according to the nuclear
      maturity status in order to the developmental evaluation as well as expression
      patterns of apoptosis-related genes using real time PCR. The fertilization and
      embryo formation rates were 60.3% and 87.5% vs.69.1% and 92.8% in test and
      control groups, respectively. Good quality embryos on day 3 were 62.2% in test
      and 69.1% in control groups. There were significant differences in the rates of
      normal fertilized as well as unfertilized oocytes between the groups. Also, mRNA
      levels of some apoptotic genes were significantly higher in the CCs obtained from
      immature oocytes among patients with premature ovarian factors (POF) rather than
      other infertility etiologies (p < 0.001). The data demonstrated the developmental
      competence of in vitro matured oocytes -even to good quality cleavage embryos- is
      not completely consistent with molecular integrity and well-mannered gene
      expression patterns resulting to ICSI success. It seems that using immature
      oocytes could be helpful for patients at risk of ovarian hyperstimulation
      syndrome (OHSS) as the same as patients with diminished ovarian reserve.

PMID- 29196050
TI  - Alpha-tocopherol succinate increases cyclooxygenase-2 activity: Tissue-specific
      action in pregnant rat uterus in vitro.
AB  - AIMS: Lipid soluble vitamin E plays a role in several physiological mechanisms,
      however, the mechanism of this action is controversial. We investigated how
      tocopherol (alpha-tocopherol acid succinate) influences the effects of
      cyclooxygenase inhibitors (COXi) in the smooth muscles. MAIN METHODS: The
      contractility of the samples from 22-day-pregnant myometrium and non-pregnant
      myometrium and trachea was determined in an isolated organ bath in vitro. The
      activity of cyclooxygenase enzymes (COX) was also measured in the tissues. KEY
      FINDINGS: Diclofenac (10-9-10-5M) and rofecoxib (10-10-10-5M) decreased the
      contractions in non-pregnant and 22-day-pregnant uteri. Tocopherol (10-7M)
      increased the relaxant effect only in pregnant uteri. Both diclofenac (10-9-10
      5M) and rofecoxib (10-10-10-5M) reduced the tracheal tones, while they were
      slightly intensified by pretreatment with tocopherol (10-7M). Tocopherol enhanced
      the contractions of pregnant uteri. Tocopherol (10-7M) itself can induce the
      cyclooxygenase activity and shift the COX-1 and COX-2 ratio to COX-2. The lowest
      COX activity was found in non-pregnant uteri, while the highest one was in the
      trachea. SIGNIFICANCE: The COX enzymes, especially COX-2, play an important role
      in the contraction of pregnant uteri in rat. Tocopherol has a tissue specific COX
      2 activity increasing effect in pregnant rat uterus but has no such action in non
      pregnant uteri or tracheal tissue. Hereby, tocopherol may intensify selectively
      the uterine relaxing effect of COX-2 inhibitors in preterm contractions. However,
      tocopherol can enhance the contractile response of pregnant uterus that may
      increase the risk of premature contractions.

PMID- 29196051
TI  - Lycium barbarum polysaccharides improve CCl4-induced liver fibrosis, inflammatory
      response and TLRs/NF-kB signaling pathway expression in wistar rats.
AB  - Lycium barbarum polysaccharides (LBPs) have multiple biological and
      pharmacological functions, including antioxidant, anti-inflammatory and
      anticancer activities. This research was conducted to evaluate whether LBPs could
      alleviate carbon tetrachloride (CCl4)-induced liver fibrosis and the underlying
      signaling pathway mechanism. Fifty male wistar rats were randomly allocated to
      five groups (n=10): control, CCl4 and CCl4 with 400, 800 or 1600mg/kg LBPs,
      respectively. Each wistar rat from each group was used for blood and tissue
      collections at the end of experiment. The results showed that CCl4 induced liver
      fibrosis as demonstrated by increasing histopathological damage, alpha-smooth
      muscle actin expression, aspartate transaminase activities, alkaline phosphatase
      activities and alanine aminotransferase activities. LBPs supplementation
      alleviated CCl4-induced liver fibrosis as demonstrated by reversing the above
      parameters. In addition, CCl4 treatment induced the oxidative injury, increased
      the mRNA levels of tumor necrosis factor-alpha, monocyte chemoattractant protein
      1 and interleukin-1beta, and up-regulated the protein expressions of toll-like
      receptor 4 (TLR4), TLR2, myeloid differentiation factor 88, nuclear factor-kappa
      B (NF-kB) and p-p65. LBPs supplementation alleviated CCl4-induced oxidative
      injury, inflammatory response and TLRs/NF-kB signaling pathway expression by
      reversing the above some parameters. These results suggest that the alleviating
      effects of LBPs on CCl4-induced liver fibrosis in wistar rats may be through
      inhibiting the TLRs/NF-kB signaling pathway expression.

PMID- 29196052
TI  - Ferulic acid-loaded nanostructured lipid carriers: A promising nanoformulation
      against the ischemic neural injuries.
AB  - AIMS: Treatment of the ischemic stroke has remained a major healthcare challenge.
      The phenolic compound, ferulic acid (FA), has shown promising antioxidant and
      neuroprotective effects, however, low bioavailability may negatively affect its
      efficiency. This, prompted us to incorporate FA into the nanostructured lipid
      carriers (FA-NLCs) and evaluate its therapeutic potential in in vitro and in vivo
      models of ischemic stroke. MAIN METHODS: FA-NLCs were prepared by high-pressure
      homogenization followed by physicochemical characterization, evaluation of the
      bioactivity of FA-NLCs in oxygen-glucose deprivation (OGD) and global cerebral
      ischemia/reperfusion (I/R) injury and implication of phosphatidylinositol 3
      kinase (PI3K) pathway in this regard. KEY FINDINGS: Formation of FA-NLCs which
      exhibited a controlled release profile, was confirmed by scanning electron
      microscope and differential scanning calorimetry. 1- and 8-h OGD followed by 24h
      re-oxygenation significantly reduced PC12 cell viability, increased lactate
      dehydrogenase activity and number of condensed nuclei, and induced oxidative
      stress as revealed by increased malondialdehyde and decreased glutathione content
      and superoxide dismutase and catalase activities. FA (80 and 100MUM) reduced the
      cytotoxicity, oxidative stress, and cellular damage only after 1-h OGD, while, FA
      NLCs (containing 80 and 100MUM of FA) were effective at both time points.
      Intravenous injections of FA-NLCs (20 and 25mg/kg) into rats significantly
      attenuated I/R-induced neurobehavioural deficits, cellular damage, and oxidative
      stress, while, FA failed. Pre-treatment with PI3K inhibitor, LY294002, abolished
      the protective effects against OGD or I/R. SIGNIFICANCE: FA-NLCs by improving the
      pharmacological profile of FA and activating PI3K pathway might be of therapeutic
      value in cerebral stroke.

PMID- 29196053
TI  - Centchroman regulates breast cancer angiogenesis via inhibition of HIF
      1alpha/VEGFR2 signalling axis.
AB  - AIMS: Angiogenesis is a recognized hallmark of cancer which promotes cancer cell
      progression and metastasis. Inhibition of angiogenesis to attenuate cancer growth
      is becoming desirable strategy for breast cancer management. The present study is
      aimed to investigate the antiangiogenic efficacy of a novel selective estrogen
      receptor modulator Centchroman (CC) on human breast cancer cells. MAIN METHODS:
      Effect of CC on cell viability was evaluated using Sulforhodamine B assay.
      Endothelial cell proliferation, wound healing, Boyden chamber cell invasion, tube
      formation and chorioallantoic membrane (CAM) assays were performed to assess the
      effect of CC on migration, invasion and angiogenesis. Apoptosis, reactive oxygen
      species generation, caspase-3/7 and intracellular calcium ion level were measured
      through flow cytometry. Expression levels of HIF-1alpha, VEGF, VEGFR2, AKT and
      ERK were assessed by western blot analysis. KEY FINDINGS: CC selectively induces
      apoptosis in human breast cancer cells without affecting non-tumorigenic breast
      epithelial cells MCF-10A. Moreover, it inhibits migratory, invasive and
      mammosphere forming potential of breast cancer. Furthermore, CC also inhibited
      VEGF-induced migration, invasion and tube formation of HUVECs in vitro. CC
      effectively inhibited neovasculature formation in chicken CAM. Western blot
      analysis demonstrated that CC inhibited expression of HIF-1alpha and its
      downstream target VEGF. Interestingly, CC also suppressed VEGFR2 phosphorylation
      and consequently attenuated AKT and ERK phosphorylation. SIGNIFICANCE: Our
      findings suggest that CC downregulates VEGF-induced angiogenesis by modulating
      HIF-1alpha/VEGFR2 pathway and recommend it (CC) as a potential therapeutic drug
      for breast cancer treatment.

PMID- 29196054
TI  - Circular economy of plastic packaging: Current practice and perspectives in
      Austria.
AB  - Plastics, especially from packaging, have gained increasing attention in waste
      management, driving many policy initiatives to improve the circularity of these
      materials in the economy to increase resource efficiency. In this context, the EU
      has proposed increasing targets to encourage the recycling of (plastic)
      packaging. To accurately calculate the recycling rates, detailed information on
      the flows of plastic packaging is needed. Therefore, the aim of this paper is to
      quantitatively and qualitatively investigate the waste management system for
      plastic packaging in Austria in 2013 using material flow analysis, taking into
      account the used product types and the polymer composition. The results show that
      300,000 +/- 3% t/a (35 kg/cap.a) of waste plastic packaging were produced, mainly
      composed of large and small films and small hollow bodies, including PET bottles.
      Correspondingly, the polymer composition of the waste stream was dominated by
      LDPE (46% +/- 6%), PET (19% +/- 4%) and PP (14% +/- 6%). 58% +/- 3% was collected
      separately, and regarding the final treatment, 26% +/- 7% of the total waste
      stream was recovered as re-granulates, whereas the rest was thermally recovered
      in waste-to-energy plants (40% +/- 3%) and the cement industry (33% +/- 6%). The
      targets set by the EU and Austria were reached comfortably, although to reach the
      proposed future target major technological steps regarding collection and sorting
      will be needed. However, the current calculation point of the targets, i.e. on
      the input side of the recycling plant, is not deemed to be fully in line with the
      overall objective of the circular economy, namely to keep materials in the
      economy and prevent losses. It is therefore recommended that the targets be
      calculated with respect to the actual output of the recycling process, provided
      that the quality of the output products is maintained, to accurately assess the
      performance of the waste management system.

PMID- 29196055
TI  - Pyrolysis kinetic evaluation by single-step for waste wood from reforestation.
AB  - The objective of this study was to evaluate the kinetic parameters of pyrolysis
      of waste wood from reforestation: Eucalyptus benthamii (EB), Eucalyptus dunnii
      (ED) and Pinus elliottii (PN). The kinetic study was performed using the
      Friedman, Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS), Starink, and
      Vyazovkin methods from the experimental data at four heating rates (5, 10, 20 and
      30  degrees C min-1). The Friedman method presented higher activation energy
      values (Ea) when compared to the other methods (EaEB = 142.98 kJ mol-1, EaED =
      147.71 kJ mol-1, EaPN = 155.46 kJ mol-1). The KAS, Starink and Vyazovkin methods
      resulted in approximate values of activation energy (EaEB = 132.83-133.31 kJ mol
      1, EaED = 137.51-137.98 kJ mol-1, EaPN = 145.24-145.70 kJ mol-1) due to the
      approximation equations with lowest relative errors. The simulation of curves
      using the kinetic parameters obtained with the Vyazovkin method showed that the
      decomposition process of EB and ED occurs as a multi-step process resulting in an
      unsatisfactory result for the simulation. On the other hand, for PN a
      satisfactory fit to the experimental data was obtained, which demonstrates its
      suitability for application to the modeling of thermochemical systems.

PMID- 29196056
TI  - Modeling the fate and end-of-life phase of engineered nanomaterials in the
      Japanese construction sector.
AB  - To date construction materials that contain engineered nanomaterials (ENMs) are
      available at the markets, but at the same time very little is known about their
      environmental fate. Therefore, this study aimed at modeling the potential fate of
      ENMs by using the example of the Japanese construction sector and by conducting a
      dynamic material flow analysis. Expert interviews and national reports revealed
      that about 3920-4660 tons of ENMs are annually used for construction materials in
      Japan. Nanoscale TiO2, SiO2, Al2O3 and carbon black have already been applied for
      decades to wall paints, road markings or concrete. The dynamic material flow
      model indicates that in 2016 about 95% of ENMs, which have been used since their
      year of market penetration, remained in buildings, whereas only 5% ended up in
      the Japanese waste management system or were diffusely released into the
      environment. Considering the current Japanese waste management system, ENMs were
      predicted to end up in recycled materials (40-47%) or in landfills (36-41%). It
      was estimated that only a small proportion was used in agriculture (5-7%, as ENM
      containing sewage sludges) or was diffusely released into soils, surface waters
      or the atmosphere (5-19%). The results indicate that ENM release predominantly
      depend on their specific applications and characteristics. The model also
      highlights the importance of adequate collection and treatment of ENM-containing
      wastes. In future, similar dynamic flow models for other countries should
      consider, inasmuch as available, historical data on ENM production (e.g. like
      declaration reports that are annually published by relevant public authorities or
      associations), as such input data is very important regarding data reliability in
      order to decrease uncertainties and to continuously improve model accuracy. In
      addition, more environmental monitoring studies that aim at the quantification of
      ENM release and inadvertent transfer, particularly triggered by waste treatment
      processes, would be needed in order to validate such models.

PMID- 29196057
TI  - Organic Electronics for Point-of-Care Metabolite Monitoring.
AB  - In this review we focus on demonstrating how organic electronic materials can
      solve key problems in biosensing thanks to their unique material properties and
      implementation in innovative device configurations. We highlight specific
      examples where these materials solve multiple issues related to complex sensing
      environments, and we benchmark these examples by comparing them to state-of-the
      art commercially available sensing using alternative technologies. We have
      categorized our examples by sample type, focusing on sensing from body fluids in
      vitro and on wearable sensors, which have attracted significant interest owing to
      their integration with everyday life activities. We finish by describing a future
      trend for in vivo, implantable sensors, which aims to build on current progress
      from sensing in biological fluids ex vivo.

PMID- 29196058
TI  - Comparison of dystonia between Parkinson's disease and atypical parkinsonism: The
      clinical usefulness of dystonia distribution and characteristics in the
      differential diagnosis of parkinsonism.
AB  - OBJECTIVE: Dystonia is occasionally found in patients with Parkinson's disease
      (PD) and atypical parkinsonisms. However, systematic comparative analysis of the
      association between dystonia and parkinsonism have seldom been reported. The
      goals of this study are to compare the clinical characteristics and distributions
      of dystonia between PD, multiple system atrophy (MSA), progressive supranuclear
      palsy (PSP) and corticobasal degeneration (CBD). METHODS: We prospectively
      enrolled 176 patients who presented with dystonia and parkinsonism out of 1278
      patients with parkinsonism. We analyzed the clinical features of dystonia and
      parkinsonism. RESULTS: The frequencies of dystonia were 11.0% in PD, 20.9% in
      MSA, 40.7% in PSP and 66.7% in CBD. Dystonia symptoms were most frequent in CBD
      and relatively more frequent in PSP and MSA (p<0.001). Moreover, multiple types
      of dystonia occurred most frequently in MSA (p=0.034). According to the
      distribution of dystonia, cranio-facial dystonia (CFD) and cervical dystonia (CD)
      were more frequently observed in atypical parkinsonism (p=0.001). In contrast,
      limb dystonia (LD) was more frequently observed in both PD and CBD, and truncal
      dystonia (TD) was more frequently detected in PD (p<0.001). Levodopa medication
      related dystonia was markedly more frequent in PD than in atypical parkinsonism
      (p=0.030). CONCLUSIONS: In this long-term, observational, prospective study, we
      concluded that levodopa medication related LD and TD were more frequently
      observed in PD than in atypical parkinsonism. Conversely, levodopa medication non
      related CFD and CD were more frequently observed in atypical parkinsonism, and
      coexisting of some types of multiple dystonia may be unique features of atypical
      parkinsonism. TD or multiple types of LD, might be representative of PD rather
      than atypical parkinsonism.

PMID- 29196059
TI  - Importance rating of risk factors of ischemic stroke in patients over 85 years
      old in the polish population.
AB  - INTRODUCTION: The European population is aging and the number of elderly patients
      suffering from ischemic brain stroke increases. A better knowledge of the
      correlation between the risk factors and the course of the disease in old people
      may be useful for planning medical care and prophylactic strategies. AIM: This
      prospective study aimed to perform a demographic and clinical analysis of the
      etiology of ischemic stroke, survival rate and severity of post-stroke disability
      in patients who developed ischemic stroke at the age of over 85 years in the
      Polish population. METHOD: The study group consisted of 159 patients over 85
      years old with ischemic stroke. The prevalence of risk factors such as sex,
      hypertension, hyperlipidemia, atrial fibrillation, heart failure and diabetes was
      evaluated. The outcome was assessed using the Barthel scale and the National
      Institutes of Health Stroke Scale. RESULTS: The most common risk factors of
      ischemic stroke were hypertension and atrial fibrillation. Patients with atrial
      fibrillation had a more severe course of ischemic stroke. CONCLUSION: The course
      of brain stroke in the Polish population is more severe in patients over 85 years
      old than in younger ones. The key risk factor in this group is atrial
      fibrillation.

PMID- 29196060
TI  - miR-365 promotes diabetic retinopathy through inhibiting Timp3 and increasing
      oxidative stress.
AB  - miRs play critical roles in oxidative stress-related retinopathy pathogenesis.
      miR-365 was identified in a previously constructed library from glyoxal-treated
      rat Muller cell. This report explores epigenetic alterations in Muller cells
      under oxidative stress to develop a novel therapeutic strategy. To examine the
      miR-365 expression pattern, in situ hybridization and quantitative RT-PCR were
      performed. Bioinformatical analysis and dual luciferase report assay were applied
      to identify and confirm target genes. Streptozotocin (STZ)-treated rats were used
      as the diabetic retinopathy (DR) model. Lentivirus-mediated anti-miR-365 was
      delivered subretinally and intravitreally into the rats' eyes. The functional and
      structural changes were evaluated by electroretinogram (ERG), histologically, and
      through examination of expression levels of metallopeptidase inhibitor 3 (Timp3),
      glial fibrillary acidic protein (Gfap), recoverin (Rcvrn) and vascular endothelia
      growth factor A (Vegfa). Oxidative stress factors and pro-inflammatory cytokines
      were analyzed. miR-365 expression was confirmed in the glyoxal-treated rat Muller
      cell line (glyoxal-treated rMC-1). In the retina, miR-365 mainly localized in the
      inner nuclear layer (INL). The increased miR-365 participated in Muller cell
      gliosis through oxidative stress aggravation, as observed in glyoxal-treated rMC
      1 and DR rats before 6 weeks. Timp3 was a target and negatively regulated by miR
      365. When miR-365 was inhibited, Timp3 expression was upregulated, Muller cell
      gliosis was alleviated, and retinal oxidative stress was attenuated. Visual
      function was also partially rescued as detected by ERG. miR-365 was found to be
      highly expressed in the retina and the abnormality of miR-365/Timp3 pathway is
      closely related to the pathology, like Muller gliosis, and the visual injury in
      DR. The mechanism might be through oxidative stress, and miR-365/Timp3 could be a
      potential therapeutic target for treating DR.

PMID- 29196061
TI  - Direct regulation of p190RhoGEF by activated Rho and Rac GTPases.
AB  - Rho family GTPases regulate a wide range of cellular processes. This includes
      cellular dynamics where three subfamilies, Rho, Rac, and Cdc42, are known to
      regulate cell shape and migration though coordinate action. Activation of Rho
      proteins largely depends on Rho Guanine nucleotide Exchange Factors (RhoGEFs)
      through a catalytic Dbl homology (DH) domain linked to a pleckstrin homology (PH)
      domain that subserves various functions. The PH domains from Lbc RhoGEFs, which
      specifically activate RhoA, have been shown to bind to activated RhoA. Here,
      p190RhoGEF is shown to also bind Rac1.GTP. Crystal structures reveal that
      activated Rac1 and RhoA use their effector-binding surfaces to associate with the
      same hydrophobic surface on the PH domain. Both activated RhoA and Rac1 can
      stimulate exchange of nucleotide on RhoA by localization of p190RhoGEF to its
      substrate, RhoA.GDP, in vitro. The binding of activated RhoA provides a mechanism
      for positive feedback regulation as previously proposed for the family of Lbc
      RhoGEFs. In contrast, the novel interaction between activated Rac1 and p190RhoGEF
      reveals a potential mechanism for cross-talk regulation where Rac can directly
      effect stimulation of RhoA. The greater capacity of Rac1 to stimulate p190RhoGEF
      among the Lbc RhoGEFs suggests functional specialization.

PMID- 29196063
TI  - Childhood maltreatment and non-suicidal self-injury: clinical implications.

PMID- 29196062
TI  - Childhood maltreatment and non-suicidal self-injury: a systematic review and meta
      analysis.
AB  - BACKGROUND: Non-suicidal self-injury is being increasingly recognised as a
      prominent public health concern. Identification of early and modifiable risk
      factors is necessary to advance the screening and intervention efforts,
      particularly early detection of at-risk individuals. We aimed to examine
      childhood maltreatment, including its specific subtypes, in relation to non
      suicidal self-injury. METHODS: We did a comprehensive meta-analysis of childhood
      maltreatment (overall, sexual abuse, physical abuse and neglect, and emotional
      abuse and neglect) in association with non-suicidal self-injury. We also provided
      a qualitative review of mediators and moderators of this association. We
      identified relevant articles published from inception to Sept 25, 2017, through a
      systematic search of Embase, MEDLINE, and PsycINFO. We extracted continuous and
      categorical data and assessed for potential moderators using ten study
      characteristics. We generated random-effects models for analysis and evaluated
      for publication bias. FINDINGS: We identified 71 publications that met
      eligibility criteria. Overall childhood maltreatment was associated with non
      suicidal self-injury (odds ratio 3.42, 95% CI 2.74-4.26), and effect sizes for
      maltreatment subtypes ranged from 1.84 (1.45-2.34) for childhood emotional
      neglect to 3.03 (2.56-3.54) for childhood emotional abuse. Publication bias was
      not evident, except in the case of childhood emotional neglect. Across multiple
      maltreatment subtypes, we found stronger associations with non-suicidal self
      injury in non-clinical samples. INTERPRETATION: With the exception of childhood
      emotional neglect, childhood maltreatment and its subtypes are associated with
      non-suicidal self-injury. Screening of childhood maltreatment history in non
      suicidal self-injury risk assessments might hold particular value in community
      settings, and increased attention to childhood emotional abuse is warranted.
      FUNDING: National Institute of Mental Health.

PMID- 29196064
TI  - Acute Management of Tension Pneumocephalus in a Pediatric Patient: A Case Report.
AB  - BACKGROUND: Tension pneumocephalus is a rare but life-threatening condition in
      which air gains entry into the cranium and exerts mass effect on the brain,
      resulting in increased intracranial pressure. It occurs most frequently secondary
      to head trauma, particularly to the orbits or sinuses. CASE REPORT: A 13-year-old
      male sustained facial trauma from a motor vehicle collision and was found to have
      tension pneumocephalus on computer tomography. The patient underwent immediate
      rapid sequence intubation without preceding positive pressure ventilation in the
      emergency department. At the time of his craniotomy, the tension pneumocephalus
      was found to have resolved and he went on to have a complete recovery. WHY SHOULD
      AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Any patient with facial or head trauma
      and pneumocephalus is at risk for the potential development of tension
      pneumocephalus. When present, we advocate that aggressive definitive airway
      management by rapid sequence intubation without preceding positive pressure
      ventilation and early surgical management should be prioritized.

PMID- 29196065
TI  - Steroidogenic enzymes, their products and sex steroid receptors during testis
      development and spermatogenesis in the domestic cat (Felis catus).
AB  - In the present study we comprehensively characterize intratesticular sex steroid
      production, metabolism and receptors in the domestic cat to elucidate the role of
      testosterone, estradiol and progesterone in testis development, steroid synthesis
      and spermatogenesis. There is a great demand for new concepts of fertility
      control in domestic (feral) cats and wild felids. The acquired knowledge will
      help to understand the regulation of spermatogenesis in felids, and may reveal
      new target points for male contraception. Progesterone and androgens are produced
      throughout all stages of testicular development; their synthesizing enzymes are
      mainly expressed in Leydig cells, and to a much lesser extent also in tubular
      cells. Aromatase (CYP19A1), the estrogen synthesizing enzyme, is only present in
      the tubuli and is first detectable in spermatocytes and round spermatids at
      puberty. As shown by elevated expression of the enzymes steroid 5-alpha-reductase
      type 1 (SRD5A) and aldo-keto-reductase family 1 member C3 (AKR1C3), the capacity
      to metabolize particular steroids increases during testis development.
      Apparently, this refers to a decreasing intra-testicular testosterone
      concentration per mg tissue with increasing testis weight during postpuberty. The
      increasing potential of sulfation of E2 by estrogen sulfotransferase (SULT1E1)
      with ongoing development might be responsible for the low level of unconjugated
      intratesticular estradiol in all stages of development probably due to
      facilitated excretion of conjugated estrogens. For the first time, expression of
      the progesterone membrane receptor components 1 and 2 (PGRMC1, PGRMC2) was
      studied in mammalian testis tissue. Both of these and also the progesterone
      receptor (PGR) are expressed depending on the developmental stage and cell type,
      suggesting an important regulatory role of progesterone in the testis. Androgen
      receptor (AR) is present in almost all cell types except for some spermatogenic
      cells. The co-localization of aromatase with estrogen receptor alpha (ESR1) in
      spermatocytes and round spermatids of domestic cat testis indicates an auto
      /paracrine function of estrogen in spermatogenesis. In summary, the testis of the
      domestic cat is an important source of sex steroids. All of them could act within
      the testis but additionally, at least androgens and estrogens are likely secreted
      by the testis, partly as conjugated steroids.

PMID- 29196067
TI  - Margin Assessment in Renal Surgery Using a Handheld Optical Coherence Tomography
      Probe.
AB  - OBJECTIVE: To assess the use of a handheld optical coherence tomography (OCT)
      probe for the evaluation of intraoperative surgical margins during partial
      nephrectomy (PN). METHODS: In an initial feasibility study, a radical nephrectomy
      specimen with a 9-cm tumor was cut into 19 sections, exposing 0 mm (n = 8), 1 mm
      (n = 6), and 2 mm (n = 5) gross margins. OCT was used to determine the margin
      width in each specimen. Second, a prospective ex vivo assessment of 15 PN tumor
      specimens was performed with OCT to determine margin status and to measure the
      attenuation coefficient of tumor and renal parenchyma. RESULTS: Median OCT margin
      width measurements for sectioned samples were 0 mm, 0.9 mm (range 0.7-2.9 mm),
      and 2.7 (range 1.65-2.8 mm) for grossly 0 mm (positive), 1 mm, and 2 mm margins,
      respectively. The difference between measurements from all margin groups was
      statistically significant (P <.04). The sensitivity and specificity for
      identifying positive margins were both 100%. In the PN specimens, OCT correctly
      found that all specimens had negative margins (within <.0001). CONCLUSION: We
      have demonstrated the feasibility of using a handheld OCT probe to assess margins
      ex vivo during PN. OCT may reduce the need for intraoperative frozen section and
      aid in minimizing parenchymal excision.

PMID- 29196066
TI  - Cough Due to TB and Other Chronic Infections: CHEST Guideline and Expert Panel
      Report.
AB  - BACKGROUND: Cough is common in pulmonary TB and other chronic respiratory
      infections. Identifying features that predict whether pulmonary TB is the cause
      would help target appropriate individuals for rapid and cost-effective screening,
      potentially limiting disease progression and preventing transmission to others.
      METHODS: A systematic literature search for individual studies to answer eight
      key questions (KQs) was conducted according to established Chest Organization
      methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and
      the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014.
      Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search
      was undertaken in March 2017. RESULTS: Even where TB prevalence is greatest, most
      individuals with cough do not have pulmonary TB. There was no evidence that 1, 3,
      or 4 weeks' duration were better predictors than cough lasting >= 2 weeks to
      screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever,
      night sweats, hemoptysis, and/or weight loss in addition to cough (any World
      Health Organization [WHO]-endorsed symptom) increases the diagnostic sensitivity
      for TB. Although the diagnostic accuracy of symptom-based screening remains low,
      the negative predictive value of the WHO-endorsed symptom screen in PLWHIV may
      help to risk-stratify individuals who are not close TB contacts and who do not
      require further testing for pulmonary TB in resource-limited settings. However,
      pregnant PLWHIV are more likely to be asymptomatic, and the WHO-endorsed symptom
      screen is not sensitive enough to be reliable. Combined with passive case finding
      (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and
      possibly when less advanced. Whether outcomes are improved or transmission is
      reduced is unclear. Screening asymptomatic patients is cost-effective only in
      populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is
      more cost-effective than clinical diagnosis. To our knowledge, no published
      comparative studies addressed whether the rate of cough resolution is a reliable
      determinant of the response to treatment or whether the rate of cough resolution
      was faster in the absence of cavitary lung disease. All studies on cough
      prevalence in Mycobacterium avium complex (MAC) lung disease, other
      nontuberculous mycobacterial infections, fungal lung disease, and paragonimiasis
      were of poor quality and were excluded from the evidence review. CONCLUSIONS: On
      the basis of relatively few studies of fair to good quality, we conclude that
      most individuals at high risk and household contacts with cough >= 2 weeks do not
      have pulmonary TB, but we suggest screening them regardless of cough duration. In
      PLWHIV, the addition of the other WHO-endorsed symptoms increases the diagnostic
      sensitivity of cough. Earlier screening of patients with cough will help diagnose
      pulmonary TB sooner but will increase the cost of screening. The addition of ACF
      to PCF will increase the number of pulmonary TB cases identified. Screening
      asymptomatic individuals is cost-effective only in groups with a very high TB
      prevalence. Data are insufficient to determine whether cough resolution is
      delayed in individuals with cavitary lung disease or in those for whom treatment
      fails because of drug resistance, poor adherence, and/or drug malabsorption
      compared with results in other individuals with pulmonary TB. Cough is common in
      patients with lung infections due to MAC, other nontuberculous mycobacteria,
      fungal diseases, and paragonimiasis.

PMID- 29196068
TI  - Incidental Discovery of Adenocarcinoma of an Augmented Bladder in a Patient With
      Myelomenigocele Undergoing Cystolithotomy.
AB  - Bladder malignancy in patients with congenital bladder anomalies who have
      undergone bladder augmentation is a rare but well-recognized condition. These
      patients present with locally advanced or metastatic disease and have poor
      survival. We report a case of a patient with myelomeningocele who was
      incidentally found to have a high-grade intestinal type adenocarcinoma of her
      bladder augment at the time of cystolithotomy. This case highlights the need to
      continue to follow patients with congenital bladder anomalies and highlights the
      lack of adequate screening methods available.

PMID- 29196069
TI  - Impact of Allergy and Resistance on Antibiotic Selection for Recurrent Urinary
      Tract Infections in Older Women.
AB  - OBJECTIVES: To review the impact of antibiotic allergy and resistance in older
      women with recurrent urinary tract infections (RUTIs) as determinants for a
      suitable oral antibiotic treatment choice. METHODS: A prospectively maintained
      database of women 65 years old and older with documented RUTIs (>=3 UTI/y) and
      trigonitis on cystoscopy was reviewed. Demographic data, known drug allergies,
      renal function, antibiotic susceptibility of most recent urine culture, allergy,
      or resistance to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones, and
      nitrofurantoin were obtained. RESULTS: From 2006 to 2014, 86 women with RUTIs met
      study criteria. Mean age was 77.9 +/- 7.8, with 94% being Caucasian. An estimated
      glomerular filtration rate >30 mL/min was noted in 94%. The percentage of women
      allergic, resistant, or both allergic and resistant to TMP-SMX was 33%, 29%, and
      15%, to fluoroquinolones was 14%, 34%, and 8.1%, or nitrofurantoin was 16%, 14%,
      and 5%, respectively. Twenty-eight percent (24 of 86) of women who were allergic
      and/or resistant to TMP-SMX and fluoroquinolones were sensitive to
      nitrofurantoin. Twenty percent (17 of 86) were allergic and/or resistant to all 3
      antibiotics. Women who were allergic or resistant to TMP-SMX had a significantly
      higher number of other antibiotic resistances compared with women sensitive to
      TMP-SMX (4.9 +/- 3.6 vs 2.1 +/- 2.3; P < .0001). Similarly, women with
      fluoroquinolone allergy or resistance had significantly more antibiotic
      resistances than those who were fluoroquinolone sensitive (5.8 +/- 3.5 vs 2.3 +/-
      2.5; P < .0001). CONCLUSION: Because of allergy and/or antibiotic resistance,
      several first-line antibiotics are not available for many older women with RUTIs.
      In nearly a third of women, nitrofurantoin was the only viable alternative.

PMID- 29196070
TI  - Evaluation of Urinary DNA Methylation as a Marker for Recurrent Bladder Cancer: A
      2-Center Prospective Study.
AB  - OBJECTIVE: To clarify the clinical utility of urinary DNA methylation for
      detection of intravesical recurrence of non-muscle invasive BCa (NMIBC), we
      performed a 2-center prospective study. PATIENTS AND METHODS: A series of 207
      self-voided urine samples were prospectively collected from 132 patients with
      NMIBC who had undergone transurethral resection of BCa. Methylation of miRNA
      genes (miR-9-3, miR-124-2, miR-124-3, and miR-137) was analyzed using bisulfite
      pyrosequencing. The primary end point was detection of intravesical recurrence;
      the secondary end point was prediction of late recurrence. The number of
      methylated genes (M-score) or quantitative level of methylation were compared
      with outcomes. RESULTS: Twenty-six urine specimens were collected on the same day
      intravesical recurrence was detected, and 14 were collected from patients whose
      recurrences were found during the subsequent follow-up period (0-632 days, mean,
      342.2 days). For detection of current recurrence, M-scores achieved 61.5%
      sensitivity and 74.0% specificity, and the area under the ROC curve was 0.71.
      Regarding prediction of late recurrence, patients with a high M-score (>=3)
      showed worse recurrence-free survival (P <.01). Multivariate analysis revealed
      that high M-scores were independently associated with current (P = .028) and late
      recurrence (P = .026). Elevated levels of urinary DNA methylation were also
      strongly associated with recurrence and radical cystectomy. CONCLUSION: Our data
      suggest that urinary methylation of miRNA genes may be a useful marker for
      detecting and predicting BCa recurrence.

PMID- 29196071
TI  - Percutaneous Tibial Nerve Stimulation in the Office Setting: Real-world
      Experience of Over 100 Patients.
AB  - OBJECTIVE: To examine the outcomes and compliance with percutaneous tibial nerve
      stimulation (PTNS) for overactive bladder (OAB) symptoms. METHODS: Adults who had
      PTNS from June 30, 2011, to October 8, 2015, were retrospectively reviewed for
      demographics, copay, travel distance, employment status, history, symptoms, and
      treatments used before, during, and after PTNS. Pearson chi-square test, Fisher
      exact test, Wilcoxon rank and paired t test were performed. RESULTS: Of 113
      patients (mean age 75 +/- 12 years), most were women (65.5%), married (78.1%),
      and retired or unemployed (80.2%). The median distance to the clinic was 8.1 mi,
      and the median copay was $0. The most common indication for PTNS was nocturia
      (92.9%) followed by OAB with urgency urinary incontinence (75.2%) and urinary
      urgency and/or frequency (24.8%). Prior treatments included anticholinergics
      (75.2%), mirabegron (36.6%), behavioral modification (29.2%), pelvic floor
      physical therapy (18.6%), and others (19.5%). Patients completed a mean of 10.5
      +/- 3 of 12 planned weekly PTNS treatments. Of 105 patients, 40 (38.1%) used
      concomitant treatments (most commonly anticholinergics). Of 87 patients, 62
      (71.3%) had decreased symptoms at 6 weeks, and of 85 patients, 60 (70.6%) had
      decreased symptoms at 12 weeks. The majority (82; 75.6%) completed all 12 weekly
      treatments and 45 (54.9%) completed 3 (median) monthly maintenance treatments.
      The most common reason for noncompliance was lack of efficacy. Visit copay,
      employment status, and distance to the clinic were not associated with failure to
      complete weekly treatments or progression to monthly maintenance. CONCLUSION:
      Although most patients' symptoms decreased after weekly PTNS, nonadherence to
      maintenance and lack of efficacy may limit long-term feasibility. Copay and
      distance traveled were not associated with noncompliance.

PMID- 29196073
TI  - Antithymocyte Globulin: Steps Toward Individualized Dosing.

PMID- 29196072
TI  - Social involvement issues in patients with Becker muscular dystrophy: A
      questionnaire survey of subjects from a patient registry.
AB  - BACKGROUND: Little is known about the relationship between Becker Muscular
      Dystrophy (BMD) and developmental problems, school life, employment, and mental
      problems. We aimed to clarify whether BMD is a risk factor for developmental
      disorders, problematic behavior, psychiatric diseases, and other social
      difficulties in school life and employment. METHODS: Adults with genetically or
      immunohistochemically confirmed BMD from the Registry of Muscular Dystrophy in
      Japan (REMUDY) were asked to complete a questionnaire regarding patient history,
      school life, employment, and mental problems. RESULTS: In total, 125 (68.3%) of
      183 participants with BMD (median age, 37.2 years) completed the questionnaire.
      Of these, ten had developmental disorders (mental retardation, autism, and speech
      disturbance). Fifty-eight (44%) experienced bullying in school, and 39 felt the
      reason for bullying was physical handicap. Sixteen participants experienced
      problematic behavior such as cutting class, domestic violence, violent incidents,
      suicide attempts, or self-mutilation. Employment histories were noted by 92
      (73%), of whom 15 could not continue to work due to physical handicaps. Fifteen
      participants had psychiatric disorders, with 5, 3 and 1 having neurosis,
      depression, and bipolar disorder, respectively. The other 6 participants with
      psychiatric disorders did not specify their diagnoses. Patients carrying a Dp140
      expression change had significantly more incidences of developmental disorders,
      but not bullying, problematic behavior, workplace difficulties, or psychiatric
      disorders. CONCLUSIONS: Patients with BMD risk bullying and workplace
      difficulties, as well as developing psychiatric disorders. Parents, teachers, and
      supporters should be mindful of the daily environment of BMD patients and provide
      support to help them cope with stress.

PMID- 29196074
TI  - Acute Kidney Injury in Pediatric Patients Receiving Allogeneic Hematopoietic Cell
      Transplantation: Incidence, Risk Factors, and Outcomes.
AB  - Acute kidney injury (AKI) is a common adverse event after hematopoietic cell
      transplantation (HCT). AKI is associated with early death or chronic kidney
      disease among transplant survivors. However, large-scale pediatric studies based
      on standardized criteria are lacking. We performed a retrospective analysis of
      1057 pediatric patients who received allogeneic HCT to evaluate the incidence and
      risk factors of AKI according to AKI Network criteria within the first 100 days
      of HCT. We also determined the effect of AKI on patient survival. The 100-day
      cumulative incidences of all stages of AKI, stage 3 AKI, and AKI requiring renal
      replacement therapy (RRT) were 68.2% +/- 1.4%, 25.0% +/- 1.3%, and 7.6% +/- .8%,
      respectively. Overall survival at 1 year was not different between patients
      without AKI and those with stage 1 or 2 AKI (66.1% versus 73.4% versus 63.9%,
      respectively) but was significantly different between patients without AKI and
      patients with stage 3 AKI with or without RRT requirement (66.1% versus 47.3%
      versus 7.5%, respectively; P < .001). Age, year of transplantation, donor type,
      sinusoidal obstruction syndrome (SOS), and acute graft-versus-host disease (GVHD)
      were independent risk factors for stages 1 through 3 AKI. Age, donor,
      conditioning regimen, number of HCTs, SOS, and acute GVHD were independent risk
      factors for AKI requiring RRT. Our study revealed that AKI was a prevalent
      adverse event, and severe stage 3 AKI, which was associated with reduced
      survival, was common after pediatric allogeneic HCT. All patients receiving
      allogeneic HCT, especially those with multiple risk factors, require careful
      renal monitoring according to standardized criteria to minimize nephrotoxic
      insults.

PMID- 29196075
TI  - Outcomes after Allogeneic Transplant in Patients with Wiskott-Aldrich Syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a
      triad of immunodeficiency, eczema, and thrombocytopenia. Currently, hematopoietic
      stem cell transplantation (HSCT) is the most reliable curative treatment with
      excellent results for patients with HLA-matched family or unrelated donors.
      However, even after fully myeloablative preparative regimens, mixed donor
      chimerism is a potential concern. We performed a retrospective chart review of 12
      children who underwent allogeneic HSCT for WAS to report our experience. The
      median age at transplant was 10.5 months (range, 3 to 39). The median nucleated
      cell dose from the marrow was 4.55 * 109/kg (range, .3 to 7.9). The median times
      to neutrophil and platelet engraftment were 19 days (range, 13 to 27) and 18.5
      days (range, 12 to 31), respectively. The rate of overall survival was 92% with
      median follow-up of 67 months (range, 3 to 146). Two patients developed grade IV
      acute graft-versus-host disease, and 1 died on day +99. Five of 12 patient's
      (42%) had mixed donor chimerism (range, 12% to 85%) at day +180. None of the
      pretransplant patient parameters was predictive of mixed chimerism. Nonetheless,
      of these 5 patients, 2 had normalization of the platelet count despite the mixed
      chimerism, 2 had full donor chimerism after receiving a second transplant with
      the same donor, and 1 remains transfusion dependent awaiting a second transplant.
      Hence, even with a significant rate of mixed chimerism, HSCT provides substantial
      benefit to WAS patients, with excellent overall survival.

PMID- 29196076
TI  - Experiences and Decision Making in Hematopoietic Stem Cell Transplant in Sickle
      Cell Disease: Patients' and Caregivers' Perspectives.
AB  - Sickle cell disease (SCD) is one of the most commonly inherited hemoglobin
      disorders that has a significant impact on quality of life, increased childhood
      morbidity, and premature mortality. Currently, hematopoietic stem cell transplant
      (HSCT) is the only treatment with a curative intent. The objective of this study
      was to determine patients' and caregivers' knowledge of HSCT, the factors
      influencing the decision to pursue HSCT, their experiences, and the impact of a
      successful HSCT on their daily living. At Children's Healthcare of Atlanta, we
      conducted a qualitative study using a semistructured interview guide of patient
      caregiver dyads and 2 focus-group sessions of adult long-term survivors of HSCT
      to elicit key factors in decision making, their experiences with HSCT, and the
      impact of HSCT. Interviews and focus-group sessions were recorded and transcribed
      verbatim. Transcripts were coded and analyzed for emerging themes using NVivo
      10.0. We enrolled 11 patient-caregiver dyads (n = 6, female patients; n = 10,
      mothers) in the qualitative interviews and 2 focus groups with 5 (n = 2, females)
      and 7 (n = 3, females) participants in each group, respectively. Our analysis
      revealed 3 prominent themes: (1) factors and concerns influencing HSCT decision
      making; (2) HSCT experiences; and (3) impact of HSCT on daily life. Participants
      reported that progression of disease-related complications and availability of a
      matched donor strongly influenced the decision to pursue HSCT. Although patients
      and caregivers had to deal with the arduous process of HSCT and transplant
      related morbidities, participants were satisfied with their decision and
      expressed no decisional regrets. Decision making for HSCT for patients with SCD
      is a complex process. Understanding the key influential factors in decision
      making and the impact HSCT has on these patients and their families will generate
      crucial insights that can guide the care of future patients and research studies.

PMID- 29196077
TI  - Impact of a Low CD34+ Cell Dose on Allogeneic Peripheral Blood Stem Cell
      Transplantation.
AB  - Although the CD34+ cell dose in allogeneic peripheral blood stem cell
      transplantation (PBSCT) is considered to be associated with transplantation
      outcomes, a lower acceptable threshold has not been defined. We retrospectively
      analyzed 2919 adult patients with hematologic malignancies who underwent related
      PBSCT in Japan between 2001 and 2014. According to the number of CD34+ cells in
      the graft, we categorized 2494 patients in the standard group (2 to 5 * 106
      cells/kg), 377 patient in the low group (1 to 2 * 106 cells/kg), and 48 patients
      in the very low group (<1 * 106 cells/kg). Compared with the standard group, the
      low and very low groups showed delayed neutrophil recovery (93.8%, 89.5%, and
      78.3%, respectively at day +28; P < .001) and platelet recovery (69.3%, 53.0%,
      and 45.5%, respectively at day +28; P < .001). The 2-year overall survival (OS)
      in the 3 groups was 45.5%, 45.3%, and 29.8%, respectively, with inferior survival
      in the very low group. However, a higher percentage of high-risk patients may
      account for the inferior survival in the very low group, and no significant
      difference in OS was found in a multivariate analysis. There were no differences
      in relapse, nonrelapse mortality, or the development of graft-versus-host disease
      among the 3 groups. In conclusion, allogeneic PBSCT with low CD34+ cell doses of
      1 to 2 * 106 cells/kg gives acceptable results, whereas further investigations
      are needed to evaluate the effects of lower doses of <1 * 106 cells/kg owing to
      the smaller number and the higher percentage of patients with adverse prognostic
      factors in this cohort.

PMID- 29196078
TI  - Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome Patients with a
      5q Deletion.
AB  - The deletion (5q) karyotype (del [5q]) in patients with myelodysplastic syndrome
      (MDS) is the most common karyotypic abnormality in de novo MDS. An increased
      number of blasts and additional karyotypic abnormalities (del [5q]+) are
      associated with a poor outcome. We analyzed the outcome of allogeneic
      hematopoietic cell transplants (HCT) in patients suffering from MDS with only del
      (5q) or del (5q)+ . A total of 162 patients, of median age 54 years (range, 9 to
      73), having MDS and del (5q) abnormalities received HCT from identical siblings
      (n = 87) or unrelated donors (n = 75). The cumulative incidence of nonrelapse
      mortality and relapse incidence at 4 years was 29% (95% CI, 22 to 36) and 46%
      (95% CI, 38 to 54), whereas the estimated 4 year survival, relapse-free and
      overall, was 25% (95% CI, 18 to 33) and 30% (95% CI, 23 to 38), respectively. In
      a multivariate analysis patients with del (5q) and a blast excess displayed
      poorer survival (hazard ratio, 2.38; 95% CI, 1.44 to 3.93; P < .001), whereas
      female recipient sex resulted in improved survival (hazard ratio, .61; 95% CI,
      .41 to .90; P = .01). We conclude that allogeneic HCT can cure a subset of
      patients with MDS and a del (5q) abnormality.

PMID- 29196079
TI  - Burnout, Moral Distress, Work-Life Balance, and Career Satisfaction among
      Hematopoietic Cell Transplantation Professionals.
AB  - A projected shortage of hematopoietic cell transplantation (HCT) health
      professionals was identified as a major issue during the National Marrow Donor
      Program/Be The Match System Capacity Initiative. Work-related distress and work
      life balance were noted to be potential barriers to recruitment/retention. This
      study examined these barriers and their association with career satisfaction
      across HCT disciplines. A cross-sectional, 90-item, web-based survey was
      administered to advanced practice providers, nurses, physicians, pharmacists, and
      social workers in 2015. Participants were recruited from membership lists of 6
      professional groups. Burnout (measured with the Maslach Burnout Inventory
      subscales of emotional exhaustion and depersonalization) and moral distress
      (measured by Moral Distress Scale-Revised) were examined to identify work-related
      distress. Additional questions addressed demographics, work-life balance, and
      career satisfaction. Of 5759 HCT providers who received an individualized
      invitation to participate, 914 (16%) responded; 627 additional participants
      responded to an open link survey. Significant differences in demographic and
      practice characteristics existed across disciplines (P < .05). The prevalence of
      burnout differed across disciplines (P < .05) with an overall prevalence of 40%.
      Over one-half of pharmacists had burnout, whereas social workers had the lowest
      prevalence at less than one-third. Moral distress scores ranged from 0 to 336 and
      varied by discipline (P < .05); pharmacists had the highest mean score (62.9 +/-
      34.8) and social workers the lowest (42.7 +/- 24.4). In multivariate and
      univariate analyses, variables contributing to burnout varied by discipline;
      however, moral distress was a significant contributing factor for all providers.
      Those with burnout were more likely to report inadequate work-life balance and a
      low level of career satisfaction; however, overall there was a high level of
      career satisfaction across disciplines. Burnout, moral distress, and inadequate
      work-life balance existed at a variable rate in all HCT disciplines, yet career
      satisfaction was high. These results suggest specific areas to address in the
      work environment for HCT health professionals, especially the need for relief of
      moral distress and a greater degree of personal time. As the creation of healthy
      work environments is increasingly emphasized to improve quality care and decrease
      costs, these findings should be used by HCT leadership to develop interventions
      that mitigate work-related distress and in turn foster recruitment and retention
      of HCT providers.

PMID- 29196082
TI  - Feasible Optimization of Stereotactic Ablative Radiotherapy Dose by Tumor Size
      for Stage I Non-small-cell Lung Cancer.
AB  - INTRODUCTION: The purpose of this study was to assess the effect of dose
      escalation of stereotactic ablative radiotherapy (SABR) by investigating the long
      term clinical outcomes of SABR for stage I non-small-cell lung cancer (NSCLC).
      METHODS: A retrospective analysis was performed on a total of 169 patients with
      178 lesions of stage I NSCLC treated with SABR at a single institution from June
      2000 to May 2015. The standard dose scheme for SABR was 48 Gy in 4 fractions
      during the early period of the analysis, but it was escalated to 60 Gy in 4
      fractions from June 2009. All failures were recorded over the follow-up period.
      RESULTS: Median follow-up time was 32 months. The 5-year overall survival rate
      was 46.7%, and the actuarial local control rate was 79.3%. Tumor size was an
      independent prognostic factor for survival. No relapse occurred in tumors <= 2 cm
      irrespective of SABR dose. Escalated doses of approximately 60 Gy in 4 fractions
      (biologically effective dose [BED] = 150 Gy10) achieved higher local control
      compared with 48 Gy in 4 fractions (BED = 106 Gy10) (76.2% vs. 60.6%) at 5-year
      follow-up (P = .022) in tumors > 2 cm. There were no differences in treatment
      related toxicities between the dose groups. Major failures consisted of distant
      metastasis to another lung parenchyma. CONCLUSION: SABR provides satisfactory
      long-term local control and high overall survival in medically inoperable stage I
      NSCLC. Tumors <= 2 cm had no local recurrence regardless of dose; whereas for
      tumors > 2 cm, an escalated BED of approximately 150 Gy10 provided significantly
      higher local tumor control.

PMID- 29196081
TI  - Prognostic Impact of Donor Source on Allogeneic Hematopoietic Stem Cell
      Transplantation Outcomes in Adults with Chronic Myelomonocytic Leukemia: A
      Nationwide Retrospective Analysis in Japan.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative
      therapeutic option for patients with chronic myelomonocytic leukemia (CMML). We
      retrospectively compared the post-transplantation outcomes of 159 patients with
      CMML who underwent allo-HSCT using 4 types of donor sources: HLA-matched related
      donor graft, unrelated bone marrow (U-BM), unrelated cord blood (U-CB), and HLA
      mismatched related donor graft. The median patient age at allo-HSCT was 54 years
      (range, 16 to 75 years). In multivariate analyses, the use of HLA-matched related
      donor grafts correlated with better overall survival than U-BM (hazard ratio
      [HR], 2.05; 95% confidence interval [CI], 1.21 to 3.48; P = .008), U-CB (HR,
      3.80; 95% CI, 2.07 to 6.95; P < .001), or HLA-mismatched related donor grafts
      (HR, 6.18; 95% CI, 2.70 to 14.15; P < .001). Mortality after the relapse or
      progression of CMML did not significantly differ among the 4 types of donor
      source. Transplantation-related mortality was highest in recipients of U-CB (HR,
      3.32; 95% CI, 1.33 to 8.26; P = .010). In patients with CMML, allo-HSCT using an
      alternative donor may contribute to durable remission; however, further
      improvements in transplantation-related mortality are required for this type of
      transplantation.

PMID- 29196083
TI  - The Good and the Bad About the 2017 American College of Physicians Osteoporosis
      Guidelines.
AB  - PURPOSE: The American College of Physicians (ACP) published a set of guidelines
      on how to prevent fractures in men and women with low bone density or
      osteoporosis. As the population ages, the overall risk of fractures increases,
      thus burdening the health care system. These guidelines review current evidence
      for osteoporosis management, providing an update to the previous 2008 ACP's
      guidelines. METHODS: The ACP put forth 6 recommendations addressing the
      complexities in osteoporosis management based on evidence available through
      October 2016 with a focus on bisphosphonates, calcium, vitamin D, and estrogen.
      Evidence was graded according to recommended strength by using the ACP standard
      methods. FINDINGS: The ACP recommends anti-osteoporosis therapy with 1 of 3
      bisphosphonates (alendronate, risedronate, or zoledronic acid) or denosumab in
      patients with osteoporosis, while excluding anabolic therapies, and recommends
      against raloxifene. Although bisphosphonates are the mainstay of treatment,
      anabolic therapy and raloxifene may be used in specific situations. Pharmacologic
      therapy is recommended for 5 years, oversimplifying length of therapy and failing
      to promote an individualized patient-centered care approach. Moreover, abrupt
      discontinuation of denosumab is associated with a decline in bone mineral density
      (BMD), which must be addressed. Routine monitoring of BMD by dual x-ray
      absorptiometry is not endorsed during treatment, which leads to underrecognition
      of management issues. Pharmacologic treatment with bisphosphonates for male
      osteoporosis is recommended, although therapies such as denosumab and
      teriparatide are excluded. Finally, the ACP recommends treatment for women aged
      >=65 years at high risk for fracture with osteopenia after a discussion of
      patient preferences, fracture risk profile, and medications. IMPLICATIONS:
      Osteoporosis management is complex. The 2017 ACP guidelines address challenges
      faced by clinicians but oversimplify more complex issues. These are among a
      number of guidelines that are available for osteoporosis management, which may be
      used in combination with other sources to assist clinicians with diagnostic and
      management strategies.

PMID- 29196080
TI  - Outcomes after Allogeneic Stem Cell Transplantation in Patients with Double-Hit
      and Double-Expressor Lymphoma.
AB  - Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are associated
      with resistance to frontline and salvage immunochemotherapy, as well as
      autologous stem cell transplantation (SCT). We hypothesized that allogeneic SCT
      (alloSCT) could overcome the chemoresistance associated with DEL/DHL. We
      retrospectively studied the impact of DEL/DHL status in a multicenter cohort of
      patients who underwent alloSCT for relapsed/refractory (rel/ref) aggressive B
      cell non-Hodgkin lymphoma (B-NHL). Seventy-eight patients transplanted at 3
      centers in whom tumor tissue was available for immunohistochemistry and
      fluorescence in situ hybridization were enrolled; 47% had DEL and 13% had DHL.
      There were no significant differences in 4-year progression-free (PFS) or overall
      survival (OS) between patients with DEL compared with patients without DEL (PFS
      30% versus 39%, P = .24; OS 31% versus 49%, P = .17) or between patients with DHL
      compared with patients without DHL (PFS 40% versus 34%, P = .62; OS 50% versus
      38%, P = .46). The lack of association between DEL or DHL and outcome was
      confirmed in multivariable models, although inadequate sample size may have
      limited our ability to detect significant differences. In our cohort alloSCT
      produced durable remissions in patients with rel/ref aggressive B-NHL
      irrespective of DEL and DHL status, justifying its consideration in the treatment
      of patients with rel/ref DEL/DHL.

PMID- 29196084
TI  - Characteristics Associated with the Choice of First Injectable Therapy Among US
      Patients With Type 2 Diabetes.
AB  - PURPOSE: The objective of this retrospective observational study was to describe
      and identify clinical and demographic characteristics associated with the choice
      of first injectable therapy (glucagon-like peptide-1 receptor agonist [GLP-1-RA]
      or basal insulin) among patients with type 2 diabetes mellitus (T2DM). METHODS:
      This analysis included adults naive to injectable therapy with T2DM who initiated
      a GLP-1-RA or basal insulin (index date) between November 2014 and February 2016
      using data from the Practice Fusion Electronic Health Record database. Patients
      with T2DM, >=1 office visit between 6 and 18 months before the index date, and
      with >=1 glycosylated hemoglobin (HbA1c) result in the 6-month preindex
      (baseline) period were included. A generalized boosted regression model was used
      to determine the patient characteristics most influential in the selection of a
      GLP-1-RA or basal insulin as first injectable therapy. Sensitivity analysis was
      performed by using bootstrapped logistic regression. FINDINGS: The study included
      3546 and 7507 GLP-1-RA and basal insulin initiators, respectively. At baseline,
      GLP-1-RA initiators were significantly younger (mean, 58 vs 63 years), had lower
      HbA1c values (mean, 8.2% vs 9.1%), lower Diabetes Complications Severity Index
      (DCSI) scores (mean, 1.0 vs 1.7), and a higher body mass index (BMI) (mean, 36 vs
      33 kg/m2) compared with basal insulin initiators. Variables selected by using the
      generalized boosted regression model with the highest relative importance (>=5%)
      in the selection of GLP-1-RA or basal insulin were HbA1c level (20.43%), BMI
      (17.73%), age (12.21%), prior prescription of a sodium-glucose cotransporter-2
      inhibitor (9.17%), and DCSI score (8.39%). The same variables, as well as race,
      were selected by using stepwise logistic regression in all the bootstrapped
      samples. Patients who were older (adjusted odds ratio [OR], 0.975 [95% CI, 0.971
      0.979]) and had higher HbA1c values (OR, 0.741 [95% CI, 0.721-0.761]) and DCSI
      scores (OR, 0.870 [95% CI, 0.848-0.892]) were significantly less likely to be
      prescribed a GLP-1-RA compared with basal insulin. Patients with higher BMI (OR,
      1.046 [95% CI, 1.040-1.053]) and previous prescription of sodium-glucose
      cotransporter-2 inhibitors (OR, 2.633 [95% CI, 2.224-2.982]) were significantly
      more likely to be prescribed a GLP-1-RA. IMPLICATIONS: The clinically relevant
      differences observed between the 2 patient populations suggest that GLP-1-RAs and
      basal insulin are prescribed to different types of patients with T2DM. Examining
      patients' demographic and clinical characteristics may be important in assisting
      physicians in the choice of patient-centered injectable treatment regimens.

PMID- 29196085
TI  - Technology Interventions for Nonadherence: New Approaches to an Old Problem.
AB  - Nonadherence to asthma medications is well recognized. Interventions to improve
      adherence, however, have been only moderately successful and are not often
      adopted because of limited provider time, training, or institutional support. The
      potential for mobile communication technology to improve adherence has gathered
      sharply growing interest. Technology-based adherence tracking devices have been
      in existence for almost 3 decades, but have only recently reached a level of
      reliability and utility to be considered in allergy practice. Adherence
      intervention technology includes smartphones, apps, and a growing number of
      potential new asthma uses such as inhaler technique assessment, portable
      fractional exhaled nitric oxide devices, and GPS activity trackers with
      environmental contaminant alerts. As technology has advanced, new capability has
      emerged including drawing information from electronic health records to tailor
      automated interventions, give real-time feedback to patients, leverage
      incentives, utilize predictive logarithms that identify patients at exacerbation
      risk, and initiate an intervention. Technology development moves faster than
      clinical trial tests of these new interventions, and gaps in evidence will need
      to be closed. As researchers establish cost effectiveness, sustainability, and
      patient and provider acceptance, technology-based adherence intervention systems
      are likely to be increasingly adopted into small and large practice settings.

PMID- 29196086
TI  - Use of the Internet by patients attending allergy clinics and its potential as a
      tool that better meets patients' needs.

PMID- 29196087
TI  - A patient with anaphylaxis to diphenhydramine without cross-reactivity to
      loratadine.

PMID- 29196088
TI  - Ivabradine improves left ventricular twist and untwist during chronic
      hypertension.
AB  - BACKGROUND: Left ventricular (LV) dysfunction develops during LV hypertrophy and
      particularly during tachycardia. Thus we investigated the effects of heart rate
      (HR) reduction with ivabradine, an If-channel blocker, on LV twist and untwist
      which represents myocardial deformation occurring during the overall systole and
      diastole and therefore provide valuable evaluation of global LV systolic and
      diastolic function. METHODS: Eight chronically instrumented pigs receiving
      continuous angiotensin II infusion during 28days to induce chronic hypertension
      and LV hypertrophy. Measurements were performed at Days 0 and 28 after stopping
      angiotensin II infusion in the presence and absence of ivabradine. RESULTS: At
      Day 0, reducing HR from 75+/-3 to 55+/-2beats/min with ivabradine did not affect
      LV twist but slowed LV untwist along with an increase in LV end-diastolic
      pressure. At Day 28, LV posterior and septal wall thickness as well as the
      estimated LV mass increased, indicating LV hypertrophy. LV twist and untwist were
      significantly reduced by 33+/-4% from 16+/-1 degrees  and 32+/-6% from -154+/-9
      degrees /s, respectively, showing global LV systolic and diastolic dysfunction.
      In this context, ivabradine decreased HR by 25% from 86+/-5beats/min and
      significantly improved LV twist from 11+/-1 to 14+/-1 degrees  and LV untwist
      from -104+/-8 to -146+/-5 degrees /s. CONCLUSIONS: Administration of ivabradine
      during chronic hypertension and LV hypertrophy improved LV twist and untwist.
      This further supports the beneficial effect of this drug on both LV systolic and
      diastolic function during the development of LV hypertrophy.

PMID- 29196089
TI  - Atrial fibrillation ablation with the second generation cryoballoon: Multicenter
      propensity score matched comparison between freezing strategies.
AB  - BACKGROUND: Second generation cryoballoon (CB-A) ablation is highly effective in
      achieving pulmonary vein (PV) isolation and freedom from atrial fibrillation
      (AF). However, the ideal freezing strategy is still under debate. Our objective
      was to investigate the efficacy and outcome between different freezing strategies
      used with the CB-A in a multicenter, matched population. METHODS: From a total
      cohort of 1018 patients having undergone CB-A ablation for drug-refractory AF,
      673 patients with follow-up >=6months were included and stratified according to
      the applied freezing strategy: bonus freeze (BF) versus single freeze (SF). Final
      population of 256 BF patients was compared with 256 propensity-score matched SF
      patients. RESULTS: BF strategy consisted of 3 different protocols: 3cycles of
      180s; 2cycles of 240s; and cycles of 240s followed by 180s in 99/256 (39%);
      42/256 (16%); and 115/256 (45%) patients, respectively. SF approach included
      cycles of 240s in 23/256 (9%), and 180s in 233/256 (91%) patients. Electrical
      isolation could be achieved in all PVs by both protocols, with shorter procedure
      and fluoroscopy times in the SF group (mean 106 vs 65min, and 18 vs 14min,
      respectively, P<0.001). Phrenic nerve palsy persisted after discharge in a total
      of 11 patients (2.1%): 4 (1.6%) in the BF group vs 7 (2.7%) in the SF group,
      P=0.5. AF-free survival was similar between the 2 groups during follow-up (mean
      18+/-10months) (log rank, P=0.6). CONCLUSIONS: CB-A ablation showed equal
      efficacy and outcome between SF and BF strategy.

PMID- 29196090
TI  - Diagnostic performance of stress perfusion cardiac magnetic resonance for the
      detection of coronary artery disease: A systematic review and meta-analysis.
AB  - INTRODUCTION: The purpose of this study was to investigate the accuracy of
      qualitative stress perfusion cardiac magnetic resonance (CMR) to diagnose
      ischemia-causing lesions according to different definitions of significant
      coronary artery disease (CAD), and magnetic field strength. METHODS: We searched
      PubMed, Web of Science, and the Cochrane Library for studies evaluating
      diagnostic performance of qualitative stress perfusion CMR for diagnosis of CAD
      versus coronary angiography or fractional flow reserve (FFR) from inception to 10
      September 2017. We used hierarchical models to synthesize the available data.
      RESULTS: Sixty-seven studies (7113 patients) met the inclusion criteria. The
      patient-based analysis of studies using FFR as the reference standard
      demonstrated a mean sensitivity of 0.90 (95% confidence interval [CI], 0.85-0.93)
      and a mean specificity of 0.85 (95% CI, 0.80-0.89). The patient-based analyses
      for detecting coronary stenosis >=50% and coronary stenosis >=70% at 1.5T and for
      detecting coronary stenosis >=50% and coronary stenosis >=70%, at 3T,
      demonstrated a mean sensitivity of 0.82 (95% CI, 0.79-0.84), 0.86 (95% CI, 0.83
      0.89), 0.90 (95% CI, 0.82-0.95), and 0.91 (95% CI, 0.79-0.96), respectively; with
      a mean specificity of 0.75 (95% CI, 0.71-0.80), 0.77 (95% CI, 0.71-0.81), 0.79
      (95% CI, 0.69-0.86), and 0.74 (95% CI, 0.59-0.85). CONCLUSION: Qualitative stress
      perfusion CMR has high accuracy for the diagnosis of CAD, irrespective of the
      reference standard and the magnet strength. Studies using FFR as the reference
      standard had higher diagnostic accuracy on a patient level compared to studies
      using coronary angiography, with a notable difference in specificity.

PMID- 29196091
TI  - Minimally invasive percutaneous transluminal renal artery stenting.
AB  - BACKGROUND: Minimally invasive percutaneous transluminal renal artery stenting
      (MIPTRS) is a method that prevents complications to the greatest extent possible.
      The present study aimed to investigate the safety and efficacy of MIPTRS
      performed in cases of renal artery stenosis with an estimated glomerular
      filtration rate (eGFR)<=45mL/min. METHODS: Cases of patients who underwent MIPTRS
      at our hospital between December 2010 and June 2015 in whom eGFR was <=45mL/min
      were retrospectively analysed. MIPTRS was performed as follows: 1) using a 4Fr
      sheathless guiding catheter in a trans-radial approach and 2) using a guiding
      catheter non-touch technique. The amount of contrast agent used was maintained at
      <=10mL with 3) carbon dioxide enhancement and 4) intravascular ultrasound guide
      stenting, and 5) a distal protection device was used. RESULTS: MIPTRS was
      performed in 22 patients (32 lesions). The pre-MIPTRS creatinine level and eGFR
      were 2.01+/-0.88mg/dL and 29.2+/-9.0mL/min/1.73m2, respectively. On postoperative
      day 2, they were 1.78+/-0.73mg/dL and 35.1+/-12.3mL/min/1.73m2; at 1month after
      the procedure, they were 1.80+/-0.74mg/dL and 33.3+/-12.3mL/min/1.73m2.
      Creatinine level did not change significantly, but eGFR was significantly
      elevated after versus before the procedure, both 2days later (p<0.01) and 1month
      later (p<0.05). CONCLUSION: The results of this study demonstrated the usefulness
      of MIPTRS for protecting renal function. This method can be safely used in
      patients with decreased renal function.

PMID- 29196092
TI  - Neurocognitive and developmental perspectives of obesity.

PMID- 29196093
TI  - Sonic hedgehog regulates the pathfinding of descending serotonergic axons in
      hindbrain in collaboration with Wnt5a and secreted frizzled-related protein 1.
AB  - Previous studies have demonstrated that both Wnt5a and Sonic hedgehog (Shh) are
      involved in regulating the pathfinding of descending serotonergic (5-HT, 5
      hydroxytryptamine) axons in an opposite manner in the brainstem. Shh and Wnt
      signaling pathways interact to guide post-crossing commissural axons, where Shh
      acts as a repellent directly and shaping the Wnt gradient indirectly by
      regulating the gradient expression of the frizzled-related protein 1 (Sfrp1).
      Whether such a mechanism functions in descending 5-HT axon guidance remains
      unknown. Here, we found that the core components of the Shh and Wnt planar cell
      polarity signaling pathways are expressed in caudal 5-HT neurons, and the
      expression gradients of Shh, Sfrp1, and Wnt5a exist simultaneously in hindbrain.
      Dunn chamber assays revealed that Sfrp1 suppressed the attractive Wnt gradient.
      Moreover, we found that Shh overexpression led to pathfinding defects in 5-HT
      axon descending, and the axonal pathfinding defects could be partially rescued by
      administration of an Sfrp1 antagonist in vivo. Biochemical evidence showed Shh
      overexpression upregulated the expression of the Sfrp1 gene and interrupted Wnt5a
      binding to Frizzled-3. Taken together, our results indicate that Shh, Sfrp1, and
      Wnt5a collaborate to direct the pathfinding of descending 5-HT axons in the
      brainstem.

PMID- 29196094
TI  - [FREGAT: French clinico-biological database dedicated to esogastric cancers].
AB  - Even though esogastric cancers are estimated at 1.5 million new cases worldwide
      with an expected 2.11 million new cases by 2025, prognosis remains poor and
      research is unsatisfactory compared to other cancers. There is an urgent need to
      intensify research via innovative and ambitious programs to improve patient's
      survival and quality of life. Incidence of esogastric cancers is particularly
      high in France, and the creation of a national clinicobiological database
      prospectively collecting epidemiological, human and social, clinical,
      pathological, biological data, sustained by biobanks of blood and tissues, is a
      critical point to improve research and care for these cancers considering all
      determinants of the disease with a more integrated approach. FREGAT
      clinicobiological database, funded and labeled by the French NCI in 2012, gathers
      the vast majority of university hospitals and cancer centers in France. This
      research relies on preexisting networks ensuring its efficacy and quality. Beyond
      significant increase of inclusions opened since January 2015, the establishment
      of public multiprivate industrial partnerships and creation of numerous French
      and European scientific projects, make FREGAT a decisive tool for research on
      esogastric cancers.

PMID- 29196095
TI  - Prognostic value of combining a quantitative image feature from positron emission
      tomography with clinical factors in oligometastatic non-small cell lung cancer.
AB  - BACKGROUND AND PURPOSE: Oligometastatic non-small cell lung cancer (NSCLC) is a
      heterogeneous condition with few known risk stratification factors. A
      quantitative imaging feature (QIF) on positron emission tomography (PET), gray
      level co-occurrence matrix energy, has been linked with outcome of nonmetastatic
      NSCLC. We hypothesized that GLCM energy would enhance the ability of models
      comprising standard clinical prognostic factors (CPFs) to stratify
      oligometastatic patients based on overall survival (OS). MATERIALS AND METHODS:
      We assessed 79 patients with oligometastatic NSCLC (<=3 metastases) diagnosed in
      2007-2015. The primary and largest metastases at diagnosis were delineated on
      pretreatment scans with GLCM energy extracted using imaging biomarker explorer
      (IBEX) software. Iterative stepwise elimination feature selection based on the
      Akaike information criterion identified the optimal model comprising CPFs for
      predicting OS in a multivariate Cox proportional hazards model. GLCM energy was
      tested for improving prediction accuracy. RESULTS: Energy was a significant
      predictor of OS (P = 0.028) in addition to the selected CPFs. The c-indexes for
      the CPF-only and CPF + Energy models were 0.720 and 0.739. CONCLUSIONS:
      Incorporating Energy strengthened a CPF model for predicting OS. These findings
      support further exploration of QIFs, including markers of the primary tumor vs.
      those of the metastatic sites.

PMID- 29196096
TI  - Effects of isolated tobacco alkaloids and tobacco products on deprivation-induced
      food intake and meal patterns in rats.
AB  - The ability of smoking to reduce body weight serves as motivation for continued
      smoking. It is unclear to what extent non-nicotine constituents in cigarettes are
      contributing to the weight-reducing effect of smoking. The purpose of the current
      study was to examine the effects of nicotine and four minor tobacco alkaloids
      (nornicotine, cotinine, anatabine, and anabasine) on food intake, one of the key
      regulators of body weight. In addition, a smokeless tobacco extract (STE) and e
      cigarette (EC) refill liquid were used to model the effects of actual tobacco
      product exposure on food intake. Male Holztman rats were trained to lever press
      for food pellets during daily 2h sessions in operant chambers. In Experiment 1,
      the effects of subcutaneous injections of saline, nicotine (0.25-1.00mg/kg),
      nornicotine (0.50-6.00mg/kg), cotinine (1.00-100.00mg/kg), anatabine (0.25
      3.00mg/kg), and anabasine (0.50-4.00mg/kg) were assessed. In Experiment 2, rats
      from Experiment 1 were used to examine the effects of nicotine, STE, and EC
      liquid. All alkaloids, except cotinine, produced a dose-dependent reduction in
      overall food intake. The highest doses of all drugs significantly reduced latency
      and response rate to obtain the first pellet. At some doses, nicotine, anatabine,
      and nornicotine reduced food intake within the first 45min without compensatory
      increases in intake later in the session. STE and EC liquid produced dose
      dependent decreases in food intake similar to nicotine alone. These data suggest
      that minor tobacco alkaloids have appetite suppressant effects and warrant
      further investigation into their effects on body weight, energy intake, and
      energy expenditure under free-feeding conditions. However, findings with STE and
      EC liquid suggest that nicotine is the primary constituent in these products to
      affect food intake, whereas levels of minor alkaloids in these products may be
      too low to influence food intake.

PMID- 29196098
TI  - Exosomes and their role in the intercellular trafficking of normal and disease
      associated prion proteins.
AB  - Over the past decade, small extracellular vesicles called exosomes have been
      observed to harbour protein and genetic cargo that can assist in health and also
      cause disease. Many groups are extensively investigating the mechanisms involved
      that regulate the trafficking and packaging of exosomal contents and how these
      processes may be deregulated in disease. Prion diseases are transmissible
      neurodegenerative disorders and are characterized by the presence of detectable
      misfolded prion proteins. The disease associated form of the prion protein can be
      found in exosomes and its transmissible properties have provided a reliable
      experimental read out that can be used to understand how exosomes and their cargo
      are involved in cell-cell communication and in the spread of prion diseases. This
      review reports on the current understanding of how exosomes are involved in the
      intercellular spread of infectious prions. Furthermore, we discuss how these
      principles are leading future investigations in developing new exosome based
      diagnostic tools and therapeutic drugs that could be applied to other
      neurodegenerative diseases.

PMID- 29196099
TI  - DKK3 overexpression attenuates cardiac hypertrophy and fibrosis in an angiotensin
      perfused animal model by regulating the ADAM17/ACE2 and GSK-3beta/beta-catenin
      pathways.
AB  - AIMS: Cardiac pressure and humoral factors induce cardiac hypertrophy and
      fibrosis, which are characterized by increased stiffness, reduced contractility
      and altered perfusion. Angiotensin II (AngII) is well known to promote this
      pathology. Angiotensin-converting enzyme (ACE) 2, which cleaves AngII and forms
      Ang-(1-7), exerts protective anti-hypertrophy and anti-fibrosis effects. A
      disintegrin and metalloproteinase 17 (ADAM17), a membrane-bound enzyme reported
      to cleave ACE2, may participate in the pathological process of AngII perfusion
      induced heart damage. However, researchers have not clearly determined whether
      dickkopf-3 (DKK3) regulates the ADAM17/ACE2 pathway and, if so, whether DKK3
      mediated regulation is related to the glycogen synthase kinase-3beta (GSK
      3beta)/beta-catenin pathway. In this study, we explored whether DKK3
      overexpression ameliorates the development of AngII-induced cardiac fibrosis and
      hypertrophy through the ADAM17/ACE2 and GSK-3beta/beta-catenin pathways. METHODS:
      Mice were injected with a DKK3-overexpressing adenovirus or vehicle and then
      infused with AngII or saline using subcutaneously implanted mini-pumps for four
      weeks. Hearts were stained with hematoxylin-eosin, Masson's trichrome and
      immunohistochemical markers for histology. Primary fibroblasts were treated with
      the adenovirus and AngII and then examined using western blotting, EdU (5-ethynyl
      2'-deoxyuridine) assays and immunofluorescence. Additionally, siRNA silencing was
      performed to study the role of DKK3 and the involved pathways. RESULTS: AngII
      induced cardiac hypertrophy and interstitial and perivascular fibrosis were less
      severe in DKK3-overexpressing mice than in control mice. Moreover, the expression
      levels of fibrotic genes, such as collagen I and III, and the hypertrophic genes
      atrial natriuretic peptide (ANP) and beta-myosin heavy chain (beta-MHC) were
      decreased. DKK3 overexpression also exerted a protective effect by inhibiting
      ADAM17 phosphorylation, thus increasing ACE2 expression and subsequently
      promoting AngII degradation. Furthermore, this process was mediated by the
      inhibition of GSK-3beta and beta-catenin and decreased translocation of beta
      catenin to the nucleus. On the other hand, the DKK3 knockdown by siRNA achieved
      opposite results. CONCLUSION: DKK3 overexpression substantially alleviated AngII
      infusion-induced cardiac hypertrophy and fibrosis by regulating ADAM17/ACE2
      pathway activity and inhibiting the GSK-3beta/beta-catenin pathway.

PMID- 29196100
TI  - Mathematical calculation of lifespan of transfused RBCs in sickle cell disease
      patients.
AB  - BACKGROUND: Transfusion of donor red blood cells (RBCs) remains an important part
      of management of sickle cell disease (SCD). However, the survival characteristics
      of transfused donor RBCs in SCD patients have not been well studied. We sought to
      calculate survival kinetics of transfused RBCs in SCD patients since it is
      unclear whether transfused RBCs get destroyed at faster rate as innocent
      bystander or persist longer due to decreased destruction capacity such as
      functional splenectomy. STUDY DESIGN: and methods Forty-one SCD patients who had
      undergone at least 3 RBC exchange procedures were inlcuded. Interval between the
      procedures, both pre-procedure and post procedure hematocrits, HbA% and HbS% were
      collected. We developed a mathematical model to calculate RBC lifespan for donor
      RBCs. RESULTS: Donor RBCs exhibited average lifespan of about 120days (121.1+/
      13.9 days), which was similar to reported survival of RBCs in normal recipients.
      However, significant variation between patients were observed with lifespan
      ranging from 75.6-148.5 days. Intrapersonal variations were small in most cases.
      CONCLUSION: The calculated survival of donor RBCs in SCD recipient, based on
      certain laboratory values, appears to be similar to that of normal recipient.
      However, inter-personal variations were large, suggesting different RBC kinetics
      in a subset of patients, which calls for further research to better understand
      underlying pathophysiology. This knowledge of RBC survival would be very helpful
      in individualized management of patients on chronic RBCx.

PMID- 29196097
TI  - The influence of tumour-derived extracellular vesicles on local and distal
      metastatic dissemination.
AB  - Extracellular vesicles (EVs) are key mediators of intercellular communication
      that have been ignored for decades. Tumour cells benefit from the secretion of
      vesicles as they can influence the behaviour of neighbouring tumour cells within
      the tumour microenvironment. Several studies have shown that extracellular
      vesicles play an active role in pre-metastatic niche formation and importantly,
      they are involved in the metastatic organotropism of different tumour types.
      Tumour-derived EVs carry and transfer molecules to recipient cells, modifying
      their behaviour through a process defined as "EV-driven education". EVs favour
      metastasis to sentinel lymph nodes and distal organs by reinforcing angiogenesis,
      inflammation and lymphangiogenesis. Hence, in this review we will summarize the
      main mechanisms by which tumour-derived EVs regulate lymph node and distal organ
      metastasis. Moreover, since some cancers metastasize through the lymphatic
      system, we will discuss recent discoveries about the presence and function of
      tumour EVs in the lymph. Finally, we will address the potential value of tumour
      EVs as prognostic biomarkers in liquid biopsies, specially blood and lymphatic
      fluid, and the use of these tools as early detectors of metastases.

PMID- 29196101
TI  - miR-135b-5p Promotes migration, invasion and EMT of pancreatic cancer cells by
      targeting NR3C2.
AB  - The exact mechanisms of metastasis for pancreatic cancer remain to be uncovered.
      This study aimed to elucidate the potential functional mechanism of miR-135b-5p
      in migration, invasion and epithelial-to-mesenchymal transition (EMT) of
      pancreatic cancer cells. By real-time PCR and analysis of GEO database, we
      determined the up-regulated expression of miR-135b-5p in pancreatic cancer
      tissues and cell lines. Clinically, highly expressed miR-135b-5p was closely
      related to advanced TNM stage, more lymph node metastasis, more distant
      metastasis and worse overall survival (OS) and disease-free survival (DFS).
      Functionally, Transwell assays indicated that miR-135b-5p was a promoter for
      migration and invasion of pancreatic cancer cells. Additionally,
      immunohistochemistry staining and Western blot showed that highly expressed miR
      135b-5p accelerated EMT process of pancreatic cancer cells. Furthermore, a series
      of experiments and rescue experiments revealed that Nuclear Receptor Subfamily 3
      Group C Member 2 (NR3C2) was the target of miR-135b-5p in pancreatic cancer
      cells, mediating the promotion effects of miR-135b-5p on the tumor cells
      migration, invasion and EMT. In conclusion, miR-135b-5p, maybe a novel
      therapeutic target for pancreatic cancer, promoted migration, invasion and EMT of
      pancreatic cancer cells by targeting NR3C2.

PMID- 29196102
TI  - Selective anticancer activity of the novel steroidal dihydropyridine
      spirooxindoles against human esophageal EC109 cells.
AB  - A series of small-molecule compounds built on steroidal dihydropyridine
      spirooxindoles has been reported previously. In this study, the compound 5l
      showed strong anti-cancer activity, especially in the esophageal cancer. Three
      esophageal squamous cell lines and paclitaxel-resistant cell line were
      investigated. The results demonstrated that compound 5l was most efficient in the
      EC109 cells, induced cell apoptosis through elevation of cellular ROS levels,
      caused G2/M phase arrest and mitochondrial dysfunction. Further study confirmed
      that the mechanism of 5l in esophageal cancer treatment was related to the Bcl-2
      family and caspase receptor-mediated apoptotic pathway.

PMID- 29196103
TI  - Cyclin-dependent kinase inhibitor 3 (CDKN3) plays a critical role in prostate
      cancer via regulating cell cycle and DNA replication signaling.
AB  - Cyclin-dependent kinase inhibitor 3 (CDKN3) is proved to be associated with the
      progressing of many cancers. Whereas, its biological effects on prostate cancer
      (PC) are less understood. To investigate the functional mechanism of CDKN3 in PC,
      we examined the expression of CDKN3 in PC tissues and analyzed the disease free
      survival time of patients. We then transfected LNCaP and PC3 cells with siRNA
      CDKN3 to silence CDKN3, and transfected 22RV1 and VCaP cells with full length
      CDKN3 cDNA for CDKN3 over-expression. Cell growth of these transfected cells were
      analyzed using CCK-8 assay. And transfected LNCaP and PC3 cells were further
      submitted to cell cycle, apoptosis, invasion and endogenous protein expression
      assays. We found that CDKN3 was highly expressed in PC and negatively correlated
      with disease relapse. And CDKN3 positively control the cell proliferation in
      prostate carcinoma cell lines. Knockdown of CDKN3 significantly promoted G1 phase
      arrest, elevated apoptosis rates, and suppressed cell invasion in both LNCaP and
      PC3 cells. Moreover, in vivo data showed that knockdown of CDKN3 expression
      dramatically inhibited the PC3 tumor growth in nude mouse model. Gene set
      enrichment analysis (GSEA) showed that cell cycle and DNA replication signaling
      were related with elevated CDKN3 expression. And results of western blot showed
      that the depletion of CDKN3 down-regulated the expression levels of cell cycle-
      and DNA replication-related proteins. In conclusion, our results highlight the
      importance of CDKN3 in PC and provide new insights into diagnostics and
      therapeutics of the PC.

PMID- 29196104
TI  - Up-regulation of long noncoding RNA FALEC predicts poor prognosis and promotes
      melanoma cell proliferation through epigenetically silencing p21.
AB  - Accumulating evidences have suggested that focally amplified lncRNA on chromosome
      1 (FALEC) serves as an oncogenic long non-coding RNA (lncRNA) and has been
      identified to be dysregulated in various tumors. However, the expression,
      clinical values, and biological function of FALEC in melanoma are still unknown.
      In this study we detected the expression level of FALEC in tumor tissues and cell
      lines and measured the prognostic value of FALEC for melanoma patients and the
      biological effects of FALEC on melanoma cell proliferation, cell cycle, and
      apoptosis. Our results indicated that FALEC was more highly expressed in melanoma
      tissues and cell lines than in non-neoplastic nevi tissues and normal cell lines.
      Moreover, functional assays showed that silenced FALEC suppressed the
      proliferation of melanoma cells, resulted in cell cycle arrest, and induced
      apoptosis. Mechanically, we discovered that FALEC boosted melanoma progression
      via epigenetically repressing p21 through recruiting EZH2 to the promoter of p21.
      Generally, our results suggested that FALEC acted as an oncogene in melanoma and
      had the potential to be a prognostic biomarker and therapeutic target for
      melanoma.

PMID- 29196105
TI  - Asiatic acid ameliorates hepatic ischemia/reperfusion injury in rats via
      mitochondria-targeted protective mechanism.
AB  - It has been proved that asiatic acid (AA) directly targets mitochondria and acts
      as a mild mitochondrial uncoupler. In this study, we aim to investigate the
      protective effects of AA against ischemia/reperfusion (I/R)-induced liver injury
      in rats and some underlying mechanisms involved were elucidated. The results
      showed that 50mg/kg AA pre-treatment significantly reduced I/R-induced liver
      damage, characterized by the decreased release of aspartate aminotransferase
      (AST) and TNF-alpha. Furthermore, AA pre-treatment dramatically inhibited the
      production of MDA and increased the hepatic SOD, catalase activities and GSH
      levels in liver tissue of I/R rats which indicated that AA ameliorated I/R
      induced liver damage by reducing oxidative stress. In isolated liver mitochondria
      in I/R rats, AA improved mitochondrial respiration, decreased mitochondrial MDA
      level, prevented I/R-induced drop of mitochondrial membrane potential (MMP) and
      increased ATP content, indicating the protective effect of AA against I/R-induced
      mitochondrial oxidative damage. In isolated liver mitochondria from normal rats,
      AA was found to effectively block succinate-driven H2O2 production no matter of
      the presence or absence of rotenone. In addition, AA showed a clear protective
      effect against anoxia/reoxygenation (A/R)-induced injury in isolated rat liver
      mitochondria when malate/glutamate were used as respiratory substrates. After AA
      treatment, mitochondrial respiratory dysfunction induced by A/R was ameliorated.
      Also, A/R-induced mitochondrial ROS generation was significantly inhibited by AA.
      In conclusion, AA can attenuate I/R-induced liver damage in rats and A/R-induced
      mitochondrial injury in isolated rat liver mitochondria by inhibiting oxidative
      stress and restoring mitochondrial function. Therefore, AA might have potential
      as a mitochondrial protective agent for use in clinical treatment of hepatic I/R
      injury.

PMID- 29196106
TI  - Xylose transport in yeast for lignocellulosic ethanol production: Current status.
AB  - Lignocellulosic ethanol has been considered as an alternative transportation
      fuel. Utilization of hemicellulosic fraction in lignocelluloses is crucial in
      economical production of lignocellulosic ethanol. However, this fraction has not
      efficiently been utilized by traditional yeast Saccharomyces cerevisiae.
      Genetically modified S. cerevisiae, which can utilize xylose, has several
      limitations including low ethanol yield, redox imbalance, and undesired
      metabolite formation similar to native xylose utilizing yeasts. Besides, xylose
      uptake is a major issue, where sugar transport system plays an important role.
      These genetically modified and wild-type yeast strains have further been
      engineered for improved xylose uptake. Various techniques have been employed to
      facilitate the xylose transportation in these strains. The present review is
      focused on the sugar transport machineries, mechanisms of xylose transport,
      limitations and how to deal with xylose transport for xylose assimilation in
      yeast cells. The recent advances in different techniques to facilitate the xylose
      transportation have also been discussed.

PMID- 29196107
TI  - Distribution of Smad mRNA and proteins in the rat brain.
AB  - Smad proteins are known to transduce the action of TGF-beta superfamily proteins
      including TGF-betas, activins, and bone morphogenetic proteins (BMPs). In this
      study, we examined the expression of Smad1, -2, -3, -4, -5, and -8 mRNA in the
      rat brain by means of RT-PCR and in situ hybridization (ISH). In addition, we
      examined the nuclear accumulation of Smad1, -2, -3, -5, and -8 proteins after
      intracerebroventricular injection of TGF-beta1, activin A, or BMP6 with
      immunohistochemistry to investigate whether TGF-beta, activin, and/or BMP
      activate Smads in the rat brain. RT-PCR analysis revealed that Smad1, -2, -3, -4,
      -5, and -8 mRNA was expressed in the brain and that the Smad3 and Smad8 mRNA
      differed in the expression level between brain regions. For example, there were
      high levels of expression of Smad3 mRNA in the cerebral cortex, caudate
      putamen/globus pallidus, and cerebellum, but low levels in the thalamus and
      midbrain. Expression of Smad8 mRNA was higher in the midbrain, cerebellum, and
      pons/medulla oblongata in comparison to the olfactory bulb, cerebral cortex,
      caudate putamen/globus pallidus, hippocampus/dentate gyrus, and thalamus. ISH
      signals for Smad1 mRNA were widely detected in the brain except for a small
      number of regions including the olfactory tubercle, posterior region of
      hypothalamus, and cerebellar nuclei. ISH signals for Smad2 mRNA were abundantly
      observed in several brain regions including the olfactory bulb, piriform cortex,
      basal ganglia, cingulate cortex, epithalamus, including the pineal gland and
      medial habenular nuclei, hypothalamus, inferior colliculi of the midbrain, and
      some nuclei in the pons, cerebellar cortex, and choroid plexus. ISH signals for
      Smad3 mRNA were also abundantly observed in several brain regions. Especially
      strong signals for Smad3 mRNA were observed in the olfactory tubercle, piriform
      cortex, basal ganglia, dentate gyrus, and cingulate cortex. ISH signals for Smad5
      and Smad8 mRNA were restricted to a small number of brain regions, the signal
      intensity of which was weak. ISH signals for Smad4 mRNA were detected in all
      regions examined. Intracerebroventricular injection of activin A induced nuclear
      accumulation of Smad2 and Smad3 immunoreactivity in neurons. In contrast,
      intracerebroventricular injection of TGF-beta1 or BMP6 did not induce nuclear
      accumulation of the immunoreactivity for any Smad in neurons. These results
      suggest that activin-Smad signaling plays an important role in brain homeostasis.

PMID- 29196108
TI  - Leaflets and continual educational offerings led to increased coverage rate of
      newborn hearing screening in Akita.
AB  - OBJECTIVE: Newborn hearing screening (NHS) has been actively performed in Japan
      since 2001. The NHS coverage rate has increased each year in Akita Prefecture. We
      analyzed the details of the NHS program and how the Akita leaflets and the many
      educational offerings about the importance of NHS led to the high NHS coverage
      rate. METHODS: A retrospective study was conducted in liveborn newborns in
      hospitals and in clinics where hearing screening was performed from the program's
      beginning in 2001 through the end of 2015. We describe the chronological history
      of NHS. The outcome data of NHS were collected from our department and analyzed.
      RESULTS: From the founding of the program in 2001 to 2015, the live birth rate in
      Akita continually declined. Nevertheless, the number of infants receiving NHS
      rose each year. Since 2012, the coverage rate of NHS has been over 90%. From 2001
      to 2015, 75,331 newborns constituted the eligible population for the NHS program.
      Since 2012, the number of NHS tests has stabilized. We prepared educational
      leaflets for Akita Prefecture early in 2002. We also provided many educational
      classes about the importance of NHS for not only pregnant women but also
      professionals including obstetricians and gynecologists, pediatricians and
      municipal staff members. The NHS program received the complete endorsement of the
      Akita Association of Obstetricians and Gynecologists in 2010. The largest
      increase in the NHS coverage rate occurred from 2001 to 2002, and the second
      largest increase occurred from 2009 to 2010. The number of participating
      institutions increased the coverage rate. The coverage rate is strongly
      correlated with the number of participating institutions (rs=0.843, p<0.001,
      Spearman's rank correlation coefficient). Comparing the coverage rate for 5 years
      before and after the Akita Association of Obstetricians and Gynecologists reached
      their consensus on the importance of NHS, the coverage rate after 2010 was
      significantly higher than before 2010 (p<0.001, paired sample t-test).
      CONCLUSION: The NHS coverage rate ultimately reached 95.4% without need for
      legislation or subsidization. The number of participating institutions increased
      each year, and the number of NHS tests and the coverage rate increased
      proportionately. The number of participating institutions statistically has a
      strong correlation with the number of NHS tests and the coverage rate. Our
      research indicates that the Akita leaflets and the provision of educational
      sessions about the importance of NHS were the most significant factors in
      establishing the high NHS coverage rate.

PMID- 29196109
TI  - Molecular Detection of the Frequent Allele F52del in Alpha 1 Antitrypsin
      Deficiency.

PMID- 29196110
TI  - Degradation of tropoelastin and skin elastin by neprilysin.
AB  - Neprilysin is also known as skin fibroblast-derived elastase, and its up
      regulation during aging is associated with impairments of the elastic fiber
      network, loss of skin elasticity and wrinkle formation. However, information on
      its elastase activity is still limited. The aim of this study was to investigate
      the degradation of fibrillar skin elastin by neprilysin and the influence of the
      donor's age on the degradation process using mass spectrometry and bioinformatics
      approaches. The results showed that cleavage by neprilysin is dependent on
      previous damage of elastin. While neprilysin does not cleave young and intact
      skin elastin well, it degrades elastin fibers from older donors, which may
      further promote aging processes. With regards to the cleavage behavior of
      neprilysin, a strong preference for Gly at P1 was found, while Gly, Ala and Val
      were well accepted at P1' upon cleavage of tropoelastin and skin elastin. The
      results of the study indicate that the progressive release of bioactive elastin
      peptides by neprilysin upon skin aging may enhance local tissue damage and
      accelerate extracellular matrix aging processes.

PMID- 29196111
TI  - The effect of early urine alkalinization on occurrence rhabdomyolysis and
      hospital stay in high dose doxylamine ingestion.

PMID- 29196112
TI  - Long-term outcomes and prognostic factors in patients with mild hemoptysis.
AB  - OBJECTIVE: The aim of this retrospective study was to observe the long-term
      outcomes of conservative treatment and bronchial artery embolization (BAE) in
      patients with mild hemoptysis and to analyze the risk factors associated with
      hemoptysis recurrence. METHODS: Patients with mild hemoptysis from January 2005
      to January 2016 were enrolled in this study. The patients' medical records,
      including smoking history, etiologic diseases, bronchoscopic findings, mortality,
      BAE information, and follow-up data of recurrent hemoptysis, were reviewed and
      analyzed. RESULTS: A total of 288 patients with mild hemoptysis were included in
      this study. Of them, 71 patients (24.7%) underwent BAE and 217 patients (75.3%)
      were treated conservatively. The clinical success rate of BAE was 98.6%, with a
      low minor complication rate of 5.6%. Bronchoscopy before treatments was performed
      in 237 patients (82.3%). Fifty-five patients (19.1%) experienced recurrent
      hemoptysis during a median follow-up period of 2.4years (interquartile range: 1.0
      4.4years). Patients who showed active bleeding or blood clots on bronchoscopy had
      a significantly lower recurrence-free survival rate than patients with no
      bronchoscopic evidence of bleeding or blood clots (p=0.012). The risk factors
      affecting recurrence were heavy smoking (p=0.002, hazard ratio [HR]: 3.57),
      aspergillosis (p=0.035, HR: 6.01), and bronchoscopic findings of active bleeding
      (p=0.016, HR: 3.29) or blood clots (p=0.012, HR: 2.77). CONCLUSIONS: The
      recurrence rate of hemoptysis was not negligible in patients with mild
      hemoptysis. BAE can be considered in patients with a high risk of recurrence.

PMID- 29196113
TI  - The impact of a CPRezyTM feedback device on the quality of chest compressions
      performed by nurses.

PMID- 29196114
TI  - Flexible, cluster-based analysis of the electronic medical record of sepsis with
      composite mixture models.
AB  - The widespread adoption of electronic medical records (EMRs) in healthcare has
      provided vast new amounts of data for statistical machine learning researchers in
      their efforts to model and predict patient health status, potentially enabling
      novel advances in treatment. In the case of sepsis, a debilitating, dysregulated
      host response to infection, extracting subtle, uncataloged clinical phenotypes
      from the EMR with statistical machine learning methods has the potential to
      impact patient diagnosis and treatment early in the course of their
      hospitalization. However, there are significant barriers that must be overcome to
      extract these insights from EMR data. First, EMR datasets consist of both static
      and dynamic observations of discrete and continuous-valued variables, many of
      which may be missing, precluding the application of standard multivariate
      analysis techniques. Second, clinical populations observed via EMRs and relevant
      to the study and management of conditions like sepsis are often heterogeneous;
      properly accounting for this heterogeneity is critical. Here, we describe an
      unsupervised, probabilistic framework called a composite mixture model that can
      simultaneously accommodate the wide variety of observations frequently observed
      in EMR datasets, characterize heterogeneous clinical populations, and handle
      missing observations. We demonstrate the efficacy of our approach on a large
      scale sepsis cohort, developing novel techniques built on our model-based
      clusters to track patient mortality risk over time and identify physiological
      trends and distinct subgroups of the dataset associated with elevated risk of
      mortality during hospitalization.

PMID- 29196115
TI  - Imaging manifestations of Behcet's disease: Key considerations and major
      features.
AB  - Behcet's disease is an autoimmune disease most commonly seen in the Middle East.
      Although primarily known with painful oral and genital ulcers, it can lead to
      vasculitis. Therefore, several associated complications such as thrombotic
      syndromes, aneurysmal arterial disease may arise. In many cases, it might be
      difficult to make the diagnosis purely based on clinical grounds; however,
      imaging plays an important role for both diagnosis and assessment of the
      disease's complications. We provide a comprehensive review of the most notable
      imaging findings of Behcet's disease.

PMID- 29196117
TI  - Magnetic alginate microfibers as scaffolding elements for the fabrication of
      microvascular-like structures.
AB  - : Traditional cell-encapsulating scaffolds may elicit adverse host responses and
      inhomogeneity in cellular distribution. Thus, fabrication techniques for cellular
      self-assembly with micro-scaffold incorporation have been used recently to
      generate toroidal cellular modules for the bottom-up construction of vascular
      like structures. The micro-scaffolds show advantage in promoting tissue
      formation. However, owing to the lack of annular cell micro-scaffolds, it remains
      a challenge to engineer micro-scale toroidal cellular modules (micro-TCMs) to
      fabricate microvascular-like structures. Here, magnetic alginate microfibers
      (MAMs) are used as scaffolding elements, where a winding strategy enables them to
      be formed into micro-rings as annular cell micro-scaffolds. These micro-rings
      were investigated for NIH/3T3 fibroblast growth as a function of surface
      chemistry and MAM size. Afterwards, micro-TCMs were successfully fabricated with
      the formation of NIH/3T3 fibroblasts and extracellular matrix layers on the three
      dimensional micro-ring surfaces. Simple non-contact magnetic assembly was used to
      stack the micro-TCMs along a micro-pillar, after which cell fusion rapidly
      connected the assembled micro-TCMs into a microvascular-like structure.
      Endothelial cells or drugs encapsulated in the MAMs could be included in the
      microvascular-like structures as in vitro cellular models for vascular tissue
      engineering, or as miniaturization platforms for pharmaceutical drug testing in
      the future. STATEMENT OF SIGNIFICANCE: Magnetic alginate microfibers functioned
      as scaffolding elements for guiding cell growth in micro-scale toroidal cellular
      modules (micro-TCMs) and provided a magnetic functionality to the micro-TCMs for
      non-contact 3D assembly in external magnetic fields. By using the liquid/air
      interface, the non-contact spatial manipulation of the micro-TCMs in the liquid
      environment was performed with a cost-effective motorized electromagnetic needle.
      A new biofabrication paradigm of construct of microvascular-like structure. The
      micro-tubal-shaped structures allowed direct cell-to-cell contact that solved
      problems of cell-encapsulating scaffolds.

PMID- 29196118
TI  - Intestinal obstruction caused by appendiceal knot.

PMID- 29196116
TI  - Contact guidance diversity in rotationally aligned collagen matrices.
AB  - : Cancer cell metastasis is responsible for approximately 90% of deaths related
      to cancer. The migration of cancer cells away from the primary tumor and into
      healthy tissue is driven in part by contact guidance, or directed migration in
      response to aligned extracellular matrix. While contact guidance has been a focus
      of many studies, much of this research has explored environments that present 2D
      contact guidance structures. Contact guidance environments in 3D more closely
      resemble in vivo conditions and model cell-ECM interactions better than 2D
      environments. While most cells engage in directed migration on potent 2D contact
      guidance cues, there is diversity in response to contact guidance cues based on
      whether the cell migrates with a mesenchymal or amoeboid migration mode. In this
      paper, rotational alignment of collagen gels was used to study the differences in
      contact guidance between MDA-MB-231 (mesenchymal) and MTLn3 (amoeboid) cells. MDA
      MB-231 cells migrate with high directional fidelity in aligned collagen gels,
      while MTLn3 cells show no directional migration. The collagen stiffness was
      increased through glycation, resulting in decreased MDA-MB-231 directionality in
      aligned collagen gels. Interestingly, partial inhibition of cell contractility
      dramatically decreased directionality in MDA-MB-231 cells. The directionality of
      MDA-MB-231 cells was most sensitive to ROCK inhibition, but unlike in 2D contact
      guidance environments, cell directionality and speed are more tightly coupled.
      Modulation of the contractile apparatus appears to more potently affect contact
      guidance than modulation of extracellular mechanical properties of the contact
      guidance cue. STATEMENT OF SIGNIFICANCE: Collagen fiber alignment in the tumor
      microenvironment directs migration, a process called contact guidance, enhancing
      the efficiency of cancer invasion and metastasis. 3D systems that assess contact
      guidance by locally orienting collagen fiber alignment are lacking. Furthermore,
      cell type differences and the role of extracellular matrix stiffness in tuning
      contact guidance fidelity are not well characterized. In this paper rotational
      alignment of collagen fibers is used as a 3D contact guidance cue to illuminate
      cell type differences and the role of extracellular matrix stiffness in guiding
      cell migration along aligned fibers of collagen. This local alignment offers a
      simple approach by which to couple collagen alignment with gradients in other
      directional cues in devices such as microfluidic chambers.

PMID- 29196119
TI  - Bone mineral density and markers of bone turnover and inflammation in diabetes
      patients with or without a Charcot foot: An 8.5-year prospective case-control
      study.
AB  - BACKGROUND AND AIMS: Charcot foot is a rare but severe complication to diabetes
      and peripheral neuropathy. It is still unclear if an acute Charcot foot has long
      term effects on the bone metabolism. To investigate this, we conducted a follow
      up study to examine if a previously acute Charcot foot has any long-term effects
      on bone mineral density (BMD) or local or systemic bone metabolism. METHODS: An
      8.5-year follow-up case-control study of 44 individuals with diabetes mellitus,
      24 of whom also had acute or chronic Charcot foot at the baseline visit in 2005
      2007, who were followed up in 2015 with DXA scans and blood samples. RESULTS: 21
      of the 44 baseline participants participated in the follow-up. There were no
      difference in the change in total hip BMD from baseline to follow-up in either
      the Charcot or the control group (p = 0.402 and 0.517), and no increased risk of
      osteoporosis in the previous Charcot feet either. From baseline to follow-up,
      there was a significant difference in the change in levels of fsRANK-L in the
      Charcot group, but not in the control group (p = 0.002 and 0.232, respectively).
      At follow-up, there were no differences in fsRANK-L between the groups. The
      fsRANK-L/OPG ratio also significantly decreased from baseline to follow-up in the
      Charcot group (3.4 versus 0.5) (p = 0.009), but not in the control group (1.3
      versus 1.1) (p = 0.302). CONCLUSION: We found that diabetes patients with an
      acute Charcot foot have an elevated fsRANK-L/OPG ratio, and that the level
      decreased from baseline to follow-up to be comparable to the level in diabetes
      patients without previous or current Charcot foot. We found no permanent effect
      of an acute Charcot foot on hip or foot BMD.

PMID- 29196120
TI  - Severe hypoglycemia is a risk factor for atrial fibrillation in type 2 diabetes
      mellitus: Nationwide population-based cohort study.
AB  - AIMS: This study investigated the association between severe hypoglycemia (SH)
      and new onset atrial fibrillation (AF) and all-cause mortality in adult patients
      with type 2 diabetes mellitus (T2DM). METHODS: Retrospective data on patients
      with T2DM aged between 30 and 75years who received healthcare checkups from
      January 1, 2005 to December 31, 2008 were analyzed using the National Health
      Insurance Database in Korea. The primary outcome was newly diagnosed non-valvular
      AF occurring after SH episode using ICD-10 codes. RESULTS: Among 1,509,280
      subjects, 10,864 (0.72%) patients had experienced SH events in the three years
      prior to health examination, and a total of 48,916 (3.24%) first-time AF episodes
      occurred during the follow-up period of 8.5years. The incidence of AF was
      significantly higher in the group with SH than the group without SH. After
      multivariable adjustment, previous SH was a significant risk factor for the
      development of AF (HR 1.10, 95% CI 1.01-1.19). All-cause mortality was also
      significantly increased in patients with previous SH events and prior SH with
      subsequent AF occurrence, compared to patients without SH events. CONCLUSIONS:
      Prior SH events were associated with a higher risk of new onset AF and all-cause
      mortality in patients with T2DM.

PMID- 29196121
TI  - Liquid chromatography-ultraviolet detection and quantification of heat-labile
      toxin produced by enterotoxigenic E. coli cultured under different conditions.
AB  - Enterotoxigenic Escherichia coli (ETEC) is the main bacterial cause of
      dehydrating infant diarrhoea in less-developed countries. Labile toxin (LT) is
      the major virulent factor of ETEC. Easy diagnostic tests are necessary to reduce
      the number of cases. Immunological methods have some drawbacks and also have
      important limitations. For that reason, a Liquid Chromatography coupled to UV
      detector technique (LC-UV) has been optimize to a rapid identification and
      quantification of LT from bacteria cultures. It is also important to know optimal
      conditions for LT and with this purpose several enterotoxigenic E. coli strains
      have been studied to determine the influence of glucose concentration and
      different culture media on LT production. LC-UV technique demonstrated to be a
      good method for LT quantification showing values of 15 ng/mL and 45 ng/mL for
      limits of detection and quantification respectively. LT quantification revealed
      that toxin production is directly related to the concentration of glucose added
      in the broth medium. Tryptic Soy Broth is the most efficient culture medium for
      E. coli growth and enterotoxin production.

PMID- 29196122
TI  - Venoms of Centruroides and Tityus species from Panama and their main toxic
      fractions.
AB  - The scorpionism in Panama is notorious for the confluence and coexistence of
      buthid scorpions from the genera Centruroides and Tityus. This communication
      describes an overview of the larger representative toxic venom fractions from
      eight dangerous buthid scorpion species of Panama: Centruroides (C. granosus, C.
      bicolor, C. limbatus and C. panamensis) and Tityus (T. (A.) asthenes, T. (A.)
      festae, T. (T.) cerroazul and T. (A.) pachyurus). Their venoms were separated by
      HPLC and the corresponding sub-fractions were tested for lethality effects on
      mice and insects. Many fractions toxic to either mice or insects, or both, were
      found and have had their molecular masses determined by mass spectrometry
      analysis. The great majority of the lethal components had a molecular mass close
      to 7000 Da, assumed to be peptides that recognize Na+-channels, responsible for
      the toxicity symptoms observed in other buthids scorpion venoms. A toxic peptide
      isolated from the venom of T. pachyurus was sequenced by Edman degradation,
      allowing the synthesis of nucleotide probe for cloning the correspondent gene.
      The mature toxin based on the cDNA sequencing has the C-terminal residue
      amidated, contains 62 amino acid packed by 4 disulfide linkages, with molecular
      mass of 7099.1 Da. This same toxic peptide seems to be present in scorpions of
      the species T. pachyurus collected in 5 different regions of Panama, although the
      overall HPLC profile is quite different. The most diverse neurotoxic venom
      components from the genus Centruroides were found in the species C. panamensis,
      whereas T. cerroazul was the one from the genus Tityus. The most common
      neurotoxins were observed in the venoms of T. festae, T. asthenes and T.
      pachyurus with closely related molecular masses of 7099.1 and 7332 Da. The
      information reported here is considered very important for future generation of a
      neutralizing antivenom against scorpions from Panama. Furthermore, it will
      contribute to the growing interest in using bioactive toxins from scorpions for
      drug discovery purposes.

PMID- 29196123
TI  - Boosting 11-oxo-beta-amyrin and glycyrrhetinic acid synthesis in Saccharomyces
      cerevisiae via pairing novel oxidation and reduction system from legume plants.
AB  - Glycyrrhetinic acid (GA) and its precursor, 11-oxo-beta-amyrin, are typical
      triterpenoids found in the roots of licorice, a traditional Chinese medicinal
      herb that exhibits diverse functions and physiological effects. In this study, we
      developed a novel and highly efficient pathway for the synthesis of GA and 11-oxo
      beta-amyrin in Saccharomyces cerevisiae by introducing efficient cytochrome P450s
      (CYP450s: Uni25647 and CYP72A63) and pairing their reduction systems from legume
      plants through transcriptome and genome-wide screening and identification. By
      increasing the copy number of Uni25647 and pairing cytochrome P450 reductases
      (CPRs) from various plant sources, the titers of 11-oxo-beta-amyrin and GA were
      increased to 108.1 +/- 4.6mg/L and 18.9 +/- 2.0mg/L, which were nearly 1422-fold
      and 946.5-fold higher, respectively, compared with previously reported data. To
      the best of our knowledge, these are the highest titers reported for GA and 11
      oxo-beta-amyrin from S. cerevisiae, indicating an encouraging and promising
      approach for obtaining increased GA and its related triterpenoids without
      destroying the licorice plant or the soil ecosystem.

PMID- 29196124
TI  - Combined engineering of disaccharide transport and phosphorolysis for enhanced
      ATP yield from sucrose fermentation in Saccharomyces cerevisiae.
AB  - Anaerobic industrial fermentation processes do not require aeration and intensive
      mixing and the accompanying cost savings are beneficial for production of
      chemicals and fuels. However, the free-energy conservation of fermentative
      pathways is often insufficient for the production and export of the desired
      compounds and/or for cellular growth and maintenance. To increase free-energy
      conservation during fermentation of the industrially relevant disaccharide
      sucrose by Saccharomyces cerevisiae, we first replaced the native yeast alpha
      glucosidases by an intracellular sucrose phosphorylase from Leuconostoc
      mesenteroides (LmSPase). Subsequently, we replaced the native proton-coupled
      sucrose uptake system by a putative sucrose facilitator from Phaseolus vulgaris
      (PvSUF1). The resulting strains grew anaerobically on sucrose at specific growth
      rates of 0.09 +/- 0.02h-1 (LmSPase) and 0.06 +/- 0.01h-1 (PvSUF1, LmSPase).
      Overexpression of the yeast PGM2 gene, which encodes phosphoglucomutase,
      increased anaerobic growth rates on sucrose of these strains to 0.23 +/- 0.01h-1
      and 0.08 +/- 0.00h-1, respectively. Determination of the biomass yield in
      anaerobic sucrose-limited chemostat cultures was used to assess the free-energy
      conservation of the engineered strains. Replacement of intracellular hydrolase
      with a phosphorylase increased the biomass yield on sucrose by 31%. Additional
      replacement of the native proton-coupled sucrose uptake system by PvSUF1
      increased the anaerobic biomass yield by a further 8%, resulting in an overall
      increase of 41%. By experimentally demonstrating an energetic benefit of the
      combined engineering of disaccharide uptake and cleavage, this study represents a
      first step towards anaerobic production of compounds whose metabolic pathways
      currently do not conserve sufficient free-energy.

PMID- 29196125
TI  - Prescription patterns and costs of antidiabetic medications in a large group of
      patients.
AB  - AIMS: To determine the prescription patterns of antidiabetic medications and the
      variables associated with their use in a Colombian population. METHODS: A cross
      sectional study using a systematized database of approximately 3.5 million
      affiliates of the Colombian Health System. Patients of both genders and all ages
      treated uninterruptedly with antidiabetic medications for three months (June
      August 2015) were included. A database was designed that included
      sociodemographic, pharmacological, comedication, and cost variables. RESULTS: A
      total of 47,532 patients were identified; the mean age was 65.5 years, and 56.3%
      were women. Among the patients, 56.2% (n=26,691) received medication as
      monotherapy. The most prescribed medications were metformin, 81.3% (n=38,664),
      insulins, 33.3% (n=15,848), and sulfonylureas, 21.8% (n=10,370). Among the
      patients, 92.8% received comedications, including antihypertensives (79.7%),
      hypolipemiants (65.5%), antiplatelet drugs (56.3%), analgesics (33.9%),
      antiulcerants (33.1%), and thyroid hormone (17.3%). The cost per 1000
      inhabitants/day was $1.21 USD for metformin, $3.89 USD for insulins, and $0.02
      USD for glibenclamide. CONCLUSIONS: Generally, rational prescription habits
      predominated, however in some cases an overuse of comedications (such as
      antiulcer drugs) and a large group of patients with high cost formulations were
      observed. Subsequent effectiveness and cost-benefit analyzes are required.

PMID- 29196127
TI  - LncRNAs and CircRNAs from the same gene: Masterpieces of RNA splicing.
AB  - Accumulating evidence has shown that lncRNAs and circRNAs are novel regulators of
      gene expression. The discovery of numerous lncRNAs and circRNAs, and
      investigation into their structures and functions will contribute to our
      understanding of the pathogenesis of diseases as well as better prevention,
      diagnosis, and treatment of diseases. There is a close relationship between
      circRNAs and lncRNAs regarding their origins and functions. Recent studies have
      shown that non-coding linear and circular transcripts can be transcribed from the
      same gene and are potential super-enhancers modulating gene transcription. In
      this review, we summarize the categories, characteristics, biological functions
      and databases of both lncRNAs and circRNAs, focusing on their transcriptions
      derived from the same gene, which might give us a deeper understanding of and
      enable us to better recognize and distinguish their physiological roles.

PMID- 29196128
TI  - Maintenance of stemness by miR-589-5p in hepatocellular carcinoma cells promotes
      chemoresistance via STAT3 signaling.
AB  - The strength and duration of STAT3 signaling are tightly controlled by multiple
      negative feedback mechanisms under physical conditions. However, how these serial
      feedback loops are simultaneously disrupted in cancers, leading to constitutive
      activation of STAT3 signaling in hepatocellular carcinoma (HCC), remains obscure.
      Here we report that miR-589-5p is elevated in HCC tissues, which is caused by
      recurrent gains. Overexpression of miR-589-5p correlates with poor overall and
      relapse-free survival in HCC patients. Upregulating miR-589-5p enhances spheroid
      formation ability, fraction of CD133 positive and side population cells,
      expression of cancer stem cell factors and the mitochondrial potential, and
      represses the apoptosis induced by doxorubicin in vitro and tumorigenicity in
      vivo in HCC cells; conversely, silencing miR-589-5p yields an opposite effect.
      Our findings further demonstrate miR-589-5p promotes the cancer stem cell
      characteristics and chemoresistance via targeting multiple negative regulators of
      STAT3 signaling pathway, including SOCS2, SOCS5, PTPN1 and PTPN11, leading to
      constitutive activation of STAT3 signaling. Collectively, our results unravel a
      novel mechanism by which miR-589-5p promotes the maintenance of stemness and
      chemoresistance in HCC, providing a potential rational registry of anti-miR-589
      5p combining with conventional chemotherapy against HCC.

PMID- 29196126
TI  - Oncogenic Kit signalling on the Golgi is suppressed by blocking secretory
      trafficking with M-COPA in gastrointestinal stromal tumours.
AB  - Most gastrointestinal stromal tumours (GISTs) are caused by constitutively active
      mutations in Kit tyrosine kinase. The drug imatinib, a specific Kit inhibitor,
      improves the prognosis of metastatic GIST patients, but these patients become
      resistant to the drug by acquiring secondary mutations in the Kit kinase domain.
      We recently reported that a Kit mutant causes oncogenic signals only on the Golgi
      apparatus in GISTs. In this study, we show that in GIST, 2-methylcoprophilinamide
      (M-COPA, also known as "AMF-26"), an inhibitor of biosynthetic protein
      trafficking from the endoplasmic reticulum (ER) to the Golgi, suppresses Kit
      autophosphorylation at Y703/Y721/Y730/Y936, resulting in blockade of oncogenic
      signalling. Results of our M-COPA treatment assay show that Kit Y703/Y730/Y936 in
      the ER are dephosphorylated by protein tyrosine phosphatases (PTPs), thus the ER
      retained Kit is unable to activate downstream molecules. ER-localized Kit Y721 is
      not phosphorylated, but not due to PTPs. Importantly, M-COPA can inhibit the
      activation of the Kit kinase domain mutant, resulting in suppression of imatinib
      resistant GIST proliferation. Our study demonstrates that Kit autophosphorylation
      is spatio-temporally regulated and may offer a new strategy for treating imatinib
      resistant GISTs.

PMID- 29196129
TI  - Stanniocalcin-1 augments stem-like traits of glioblastoma cells through binding
      and activating NOTCH1.
AB  - Glioblastoma (GBM) is a fatal tumor and comprises heterogeneous cells in which a
      subpopulation with stem cell-like properties is included. Cancer cells with stem
      cell-like properties account for tumor initiation, drug resistance and
      recurrence. To identify and characterize specific factors in regulating stem-like
      traits is critical for GBM therapeutic. Here, we showed that Stanniocalcin-1
      (STC1), a secretory glycoprotein, functions as a novel stimulator for stem-like
      traits of GBM cells. We found STC1 was prominently expressed in glioma spheres
      which are mainly comprised of glioma stem-like cells. The stem-like traits of GBM
      cells, as determined by the expression of stem cell markers, tumor-sphere
      formation efficiency and colony-forming ability, were enhanced by STC1
      overexpression and inhibited by STC1 knockdown. Furthermore, introduction of STC1
      enhanced tumorigenesis in vivo while knockdown of STC1 showed reverse effect.
      Finally, we demonstrated that STC1 interacted with the extracellular domain of
      NOTCH1 to activate NOTCH1-SOX2 signaling pathway, by which STC1 augmented the
      stem-like traits of GBM cells. Taken together, our data herein indicate that STC1
      is a novel non-canonical NOTCH ligand and acts as a crucial regulator of stemness
      in GBM.

PMID- 29196130
TI  - Subtype distribution and genetic characterizations of Blastocystis in pigs,
      cattle, sheep and goats in northeastern China's Heilongjiang Province.
AB  - Blastocystis is a common protozoan found in the surveys of human and animal fecal
      specimens. Extensive genetic diversity has been observed within the genus
      Blastocystis. At least 17 subtypes (ST) have been identified in mammals and
      birds, nine of which (ST1 to ST9) have been identified in humans. In China,
      although there have been a few reports on Blastocystis infection in humans and
      many animal species, no epidemiological data are available in either humans or
      animals in northeastern China's Heilongjiang Province. To determine infection
      rates and subtype distributions of Blastocystis in pigs, cattle, sheep and goats,
      to understand genetic characterizations and to assess zoonotic possibility of
      Blastocystis isolates, 337 fecal specimens from livestock (68 from pigs, 147 from
      cattle, 109 from sheep and 13 from goats) were collected in northeastern China's
      Heilongjiang Province. Each of them was detected for Blastocystis by PCR
      amplification of the partial SSU rRNA gene. An average infection rate of
      Blastocystis was 7.7% (26/337), and the highest infection rate was found in 9.5%
      (14/147) in cattle, followed by 8.8% (6/68) in pigs and 5.5% (6/109) in sheep.
      There was an absence of Blastocystis in goats. Five Blastocystis subtypes were
      identified: ST5 (n=6) in pigs; ST3 (n=2), ST10 (n=10) and ST14 (n=2) in cattle;
      ST1 (n=1), ST5 (n=1), ST10 (n=3) and ST14 (n=1) in sheep. 38.5% (10/26) of
      Blastocystis isolates belong to potentially zoonotic subtypes based on the
      previous findings of ST1, ST3 and ST5 in humans. This is the first report of
      Blastocystis in pigs, cattle and sheep in northeastern China's Heilongjiang
      Province. ST1, ST5 and ST14 were identified in sheep for the first time. Due to
      the low infection rate of Blastocystis and the small percentage of potentially
      zoonotic subtypes in these livestock, there is a minimal risk of zoonotic
      transmission of Blastocystis.

PMID- 29196131
TI  - Differential involvement of synovial adipokines in pain and physical function in
      female patients with knee osteoarthritis. A cross-sectional study.
AB  - OBJECTIVE: Adipokines have been reported to play a role in the development,
      progression and severity of knee osteoarthritis but the influence of the
      different adipokines are not well known. The aim of this study was to evaluate
      the association between different synovial fluid adipokines with pain and
      disability knee osteoarthritis patients. METHODS: Cross-sectional study with
      systematic inclusion of 115 symptomatic primary knee osteoarthritis female
      patients with ultrasound-confirmed joint effusion. Age, physical exercise,
      symptoms duration and different anthropometric measurements were collected.
      Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain
      and disability were assessed by WOMAC-total, -pain, -function subscales and Knee
      injury and Osteoarthritis Outcome Score (KOOS) pain and function scales. Seven
      adipokines and three inflammatory markers were measured by ELISA in synovial
      fluid. Partial Correlation Coefficient (PCC) and corresponding 95% confidence
      interval were used as a measure of association. RESULTS: Leptin, osteopontin and
      inflammatory factors, especially TNF-alpha, were associated to pain and function.
      After adjustment for potential confounders including inflammatory factors and all
      adipokines, an association was found for adiponectin with pain (PCC 0.240 [0.012,
      0.444]) and for resistin and visfatin with function (PCC 0.336 [0.117, 0.524] and
      -0.262 [-0.463, -0.036]). No other adipokines or inflammatory markers were
      statistically and independently associated. An association between physical
      exercise and pain and disability remained after adjustment, whereas an
      attenuation of the influence of anthropometric measurements was observed.
      CONCLUSIONS: Different patterns of association between synovial fluid adipokines
      were observed regarding pain and disability in knee osteoarthritis patients.
      Specifically, adiponectin was associated to pain while resistin and visfatin were
      mainly related to function.

PMID- 29196132
TI  - Association of TNF-alpha (-308 A/G) and IFN-gamma (+874 A/T) gene polymorphisms
      in response to spontaneous and treatment induced viral clearance in HCV infected
      multitransfused thalassemic patients.
AB  - BACKGROUND: Multitransfused thalassemic individuals are at high risk of
      developing transfusion transmitted Hepatitis C virus (HCV) infection. The aim of
      the study was to correlate the effects of host cytokine single nucleotide
      polymorphisms of TNF-alpha (-308 A/G) and IFN-gamma (+874 A/T) in spontaneous or
      IFN induced treatment response in the HCV infected thalassemic individuals.
      METHODS: A total of 427 HCV sero-reactive thalassemic individuals were processed
      for HCV viral genomic diversity and host gene polymorphisms analysis of TNF-alpha
      (-308 A/G) and IFN-gamma (+874 A/T). RESULTS: Out of 427 HCV sero-reactive
      individuals, 69.09% were found to be HCV RNA positive with genotype 3 as the
      predominant infecting strain (94.29%). Study highlighted that, A allele was
      significantly associated with (p < .05) spontaneous clearance of HCV infection
      and G allele was correlated with viral persistence at TNF-alpha (-308) gene
      polymorphism. Whereas in case of IFN-gamma (+874) SNPs, A allele was
      significantly responsible (p < .05) for spontaneous clearance than T allele. Our
      study also indicated that in relapsed cases, IFN-gamma (+874) T allele is more
      responsible than A allele. Though no significant correlation was found at both
      TNF-alpha (-308) and IFN-gamma (+874) gene polymorphism among SVR and relapsed
      thalassemic patients. CONCLUSION: A allele at both TNF-alpha (-308) and IFN-gamma
      (+874) were strongly associated with spontaneous clearance among this population.
      But in case of SVR and relapsed cases no significant association was found. This
      cytokine gene polymorphisms pattern will help clinicians to take an informed
      decision about therapeutic management of HCV infected thalassemic individuals.

PMID- 29196133
TI  - Rapid negative inotropic effect induced by TNF-alpha in rat heart perfused
      related to PKC activation.
AB  - Myocardial depression, frequently observed in septic shock, is mediated by
      circulating molecules such as cytokines. TNF-alpha appears to be the most
      important pro-inflammatory cytokine released during the early phase of a septic
      shock. It was previously shown that TNF-alpha had a negative inotropic effect on
      myocardium. Now, the aim of this study was to investigate the effects of the
      activation of PKC by TNF-alpha on heart function, and to determine if this
      cytokine could induce a decrease of membrane excitability. Isolated rat hearts (n
      = 6) were perfused with Tyrode solution containing TNF-alpha at 20 ng/ml during
      30 min by using a Langendorff technique. Expressions of PKC-alpha and PKC-epsilon
      were analysed by western blot on membrane and cytosol proteins extracted from
      ventricular myocardium. Patch clamp was performed on freshly isolated
      cardiomyocytes (n = 8). Compared to control situation, 30 min of TNF-alpha
      perfusion led to cardiac dysfunction with a decrease of the heart rate (-83%),
      the force (-20%) and speed of relaxation (-18%) and the coronary flow (-25%).
      This is associated with an activation and a membrane targeting of both PKC-alpha
      and PKC-epsilon isoforms in ventricle with respectively +123% and +54% compared
      to control hearts. Nevertheless, TNF-alpha had no significant effect on voltage
      gated sodium current (109.0%+/- 12.5) after addition of the cytokine when
      compared to control. These results showed that TNF-alpha had a negative inotropic
      effect on the isolated rat heart and can induce PKC activation leading to an
      impaired contractility of the heart. However the early heart dysfunction induced
      by the cytokine was not associated to a decrease of cardiomyocytes membrane
      excitability as it has been evidenced in skeletal muscle fibres.

PMID- 29196135
TI  - ESGCT 2017 in Berlin: Clear Steps Forward.

PMID- 29196134
TI  - A review of the traditional and modern uses of Salvadora persica L. (Miswak):
      Toothbrush tree of Prophet Muhammad.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvadora persica L., also known as Arak (in
      Arabic) and Peelu (in Urdu), is the most common traditional source of tooth or
      chewing stick (miswak) highly recommended by Prophet Muhammad. To date, extensive
      studies have probed primarily into the validation of its traditional uses in oral
      care. Nonetheless, there is still a dearth of updated compilation and critical
      analysis of other potential ethnopharmacological properties of S. persica. This
      review therefore aims to provide an up-to-date detailed structured description of
      the traditional uses of S. persica and a critical analysis of its modern uses,
      highlighting its phytochemistry, pharmacological properties, and bioapplications.
      MATERIALS AND METHODS: Various databases (Science Direct, PubMed, Wiley Online
      Library, and Google Scholar), books, and relevant primary sources were probed,
      surveyed, analysed, and included in this review. The literature cited in this
      review dated from 1979 to 2017. RESULTS: S. persica was found to possess a
      plethora of bioactive compounds and broad pharmacological properties, including
      antimicrobial, antioxidant, enzyme inhibitory activity, antiulcer,
      anticonvulsant, sedative, analgesic, anti-inflammatory, hypoglycemic,
      hypolipidemic, antiosteoporosis, and antitumor activities. Studies also revealed
      the potential use of S. persica as a natural food preservative and a novel
      functional food ingredient. In addition, improvement in growth and reproductive
      performances have been observed by the introduction of S. persica in animal feed.
      Lastly, S. persica has also been used in the green synthesis of nanoparticles
      showing potential biotechnological applications. CONCLUSION: S. persica showed a
      wide scope of application and its uses have been extended far beyond the initial
      traditional uses of its roots, stems, and twigs in oral care. We found a number
      of other ethnopharmacological uses and potential bioapplications of different
      parts of S. persica that warrants further investigations. Though widely studied
      using several in vitro and in vivo models, and tested clinically for oral hygiene
      mainly, several gaps and research priorities have been identified which needs to
      be addressed in future.

PMID- 29196137
TI  - Transesophageal Echocardiography for Guidance of Endovascular Stent Exclusion of
      Thoracic Aortic Thrombi: A Case Series.

PMID- 29196136
TI  - Discovery of molecular mechanism of a clinical herbal formula upregulating serum
      HDL-c levels in treatment of metabolic syndrome by in vivo and computational
      studies.
AB  - Decreased HDL cholesterol (HDL-c) is considered as an independent risk factor of
      cardiovascular disease in metabolic syndrome (Mets). Wendan decoction (WDD), a
      famous clinical traditional Chinese medicine formula in Mets in China, which can
      obviously up-regulate serum HDL-c levels in Mets. However, till now, the
      molecular mechanism of up-regulation still remained unclear. In this study, an
      integrated approach that combined serum ABCA1 in vivo assay, QSAR modeling and
      molecular docking was developed to explore the molecular mechanism and chemical
      substance basis of WDD upregulating HDL-c levels. Compared with Mets model group,
      serum ABCA1 and HDL-c levels intervened by two different doses of WDD for two
      weeks were significantly up-regulated. Then, kohonen and LDA were applied to
      develop QSAR models for ABCA1 up-regulators based flavonoids. The derived QSAR
      model produced the overall accuracy of 100%, a very powerful tool for screening
      ABCA1 up-regulators. The QSAR model prediction revealed 67 flavonoids in WDD were
      ABCA1 up-regulators. Finally, they were subjected to the molecular docking to
      understand their roles in up-regulating ABCA1 expression, which led to discovery
      of 23 ABCA1 up-regulators targeting LXR beta. Overall, QSAR modeling and docking
      studies well accounted for the observed in vivo activities of ABCA1 affected by
      WDD.

PMID- 29196138
TI  - Fifty Years: Reflections Since the First Successful Heart Transplant.

PMID- 29196139
TI  - A Rare Cause of Intermittent Dyspnea, Occasional Palpitations, and Atypical Chest
      Discomfort.

PMID- 29196140
TI  - How to Write a Research Proposal in Vascular Surgery: The Basics and Details Not
      to Forget.

PMID- 29196141
TI  - Effect of resistance training on muscle strength and rate of force development in
      healthy older adults: A systematic review and meta-analysis.
AB  - Rapid force capacity, identified by rate of rise in contractile force at the
      onset of contraction, i.e., the rate of force development (RFD), has been
      considered an important neuromuscular parameter of physical fitness in elderly
      individuals. Randomized control studies conducted in adults have found that
      resistance training may elicit different outcomes in terms of RFD and muscle
      strength. Thus, the main purpose of this study was to review systematically the
      literature for studies regarding the influence of resistance training on muscle
      strength and RFD in elderly persons. A literature search was performed in major
      electronic databases from inception to March 2017. Studies including health
      individuals with a mean age>=60years, describing the effect of resistance
      training on RFD and muscle strength were found eligible. The outcomes were
      calculated as the difference in percentage change between control and
      experimental groups (% change) and data were presented as mean+/-95% confidence
      limits. Meta-analyses were performed using a random-effects model and, in
      addition, simple and multiple meta-regression analyses were used to identify
      effects of age, training type, sessions per week and training duration on %
      change in RFD and muscle strength. Thirteen training effects were collected from
      10 studies included in the meta-analysis. The resistance training program had a
      moderate beneficial effect on both muscle strength (% change=18.40%, 95% CL 13.69
      23.30, p<0.001) and RFD (% change=26.68, 95% CL 14.41-35.52, p<0.001). Results of
      the meta-regression revealed that the variables age, training type (i.e.,
      strength and explosive), training duration (4-16weeks) and sessions per week had
      no significant effects on muscle strength and RFD improvement. Moreover, there
      was no significant relationship (p=0.073) between the changes in muscle strength
      and RFD. It can be concluded that explosive training and heavy strength training
      are effective resistance training methods aiming to improve both muscle strength
      and RFD after short-to-medium training period. However, muscle strength and RFD
      seem to adapt differently to resistance training programs, suggesting caution for
      their interchangeable use in clinical assessments of the elderly.

PMID- 29196142
TI  - New transgenic models of Parkinson's disease using genome editing technology.
AB  - INTRODUCTION: Parkinson's disease (PD) is the second most common
      neurodegenerative disorder. It is characterised by selective loss of dopaminergic
      neurons in the substantia nigra pars compacta, which results in dopamine
      depletion, leading to a number of motor and non-motor symptoms. DEVELOPMENT: In
      recent years, the development of new animal models using nuclease-based genome
      editing technology (ZFN, TALEN, and CRISPR/Cas9 nucleases) has enabled the
      introduction of custom-made modifications into the genome to replicate key
      features of PD, leading to significant advances in our understanding of the
      pathophysiology of the disease. CONCLUSIONS: We review the most recent studies on
      this new generation of in vitro and in vivo PD models, which replicate the most
      relevant symptoms of the disease and enable better understanding of the aetiology
      and mechanisms of PD. This may be helpful in the future development of effective
      treatments to halt or slow disease progression.

PMID- 29196143
TI  - Intravenous immunoglobulin G as adjuvant treatment in drug-resistant childhood
      epilepsy.
AB  - BACKGROUND: Epilepsy is the most common neurological disease in childhood;
      depending on the definition of drug-resistant epilepsy, incidence varies from 10%
      to 23% in the paediatric population. The objective of this study was to account
      for the decrease in the frequency and/or monthly duration of epileptic seizures
      in paediatric patients with drug-resistant epilepsy treated with antiepileptic
      drugs, before and after adding intravenous immunoglobulin G (iIV IgG). METHODS:
      This is an analytic, observational, retrospective case-control study. We studied
      paediatric patients with drug-resistant epilepsy who were treated with IV IgG at
      the Centro Medico Nacional 20 de Noviembre, in Mexico City, from 2003 to 2013.
      RESULTS: One hundred and sixty seven patients (19.5%) had drug-resistant epilepsy
      and 44 (5.1%) started adjuvant treatment with IV IgG. The mean age of patients at
      the beginning of treatment was 6.12 years+/-5.14); aetiology was structural
      acquired in 28 patients (73.6%), genetic in 5 (13.1%), immune in 1 (2.6%), and
      unknown in 4 (10.5%). At 2 months from starting IV IgG, seizure duration had
      reduced to 66.66%; the frequency of seizures was reduced by 64% at 4 months after
      starting treatment (P<.001). CONCLUSIONS: According to the results of this study,
      intravenous immunoglobulin may be an effective therapy for reducing the frequency
      and duration of seizures in paediatric patients with drug-resistant epilepsy.

PMID- 29196144
TI  - Spatio-temporal expression of Hexokinase-3 in the injured female rat spinal
      cords.
AB  - Hexokinase-3 (HK3) is a member of hexokinase family, which can catalyze the first
      step of glucose metabolism. It can increase ATP levels, reduce the production of
      reactive oxygen species, increase mitochondrial biogenesis, protect mitochondrial
      membrane potential and play an antioxidant role. However, the change of its
      expression in spinal cord after injury is still unknown. In this study, we
      investigated the spatio-temporal expression of HK3 in the spinal cords by using a
      spinal cord injury (SCI) model in adult female Sprague-Dawley rats. Quantitative
      reverse transcription-PCR and western blot analysis revealed that HK3 could be
      detected in sham-opened spinal cords. After SCI, it gradually increased, reached
      a peak at 7 days post-injury (dpi), and then gradually decreased with the
      prolonging of injury time, but still maintained at a higher level for up to 28
      dpi (the longest time evaluated in this study). Immunofluorescence staining
      showed that HK3 was found in GFAP+, beta-tubulin III+ and IBA-1+ cells in sham
      opened spinal cords. After SCI, in addition to the above-mentioned cells, it
      could also be found in CD45+ and CD68+ cells. These results demonstrate that HK3
      is mainly expressed in astrocytes, neurons and microglia in normal spinal cords,
      and could rapidly increase in infiltrated leukocytes, activated
      microglia/macrophages and astrocytes after SCI. These data suggest that HK3 may
      be involved in the pathologic process of SCI by promoting glucose metabolism.

PMID- 29196145
TI  - Effects of imipramine on cytokines panel in the rats serum during the drug
      treatment and discontinuation.
AB  - Time dependent sensitization (TDS) - phenomenon described originally by Chiodo
      and Antelman (1980) in context of dopamine receptors, refers to cascade of events
      that continue to develop in the organism, after the initiating stimulus is no
      longer available. Treatment could be recognized as such a initiating stimulus (in
      case of depression, example of electroconvulsive therapy would be obvious, but
      some aspects of pharmacotherapy too). The process leads to improvement, but, on
      the other hand, phenomena of kindling in recurrent depression is well known (more
      relapses and therapies make heavier and longer lasting subsequent episodes).
      Hence our interest in delayed effects of treatment. Here we report alterations in
      rat immune system after Imipramine (IMI) treatment cessation. Wistar male rats
      were treated with IMI (10 mg/kg i.p. in 2 ml/kg of saline) repeatedly for 21 days
      or once - on the last day of drug administration period. Then the 3 weeks
      discontinuation phase begun, during which, at certain time points (3 h, 72 h,
      7days, 21days) the trunk blood was collected. Tissue concentrations of IMI and
      its metabolite desipramine (DMI), as well as ACTH and various cytokines were
      measured. The IMI and DMI was detectable only 3 h after the last i.p. injection
      of the drug. Ever since the second time point (72 h of discontinuation) the
      levels of either compound were below detection threshold.There was no significant
      changes in ACTH levels between rat groups, although IMI seemed to attenuate
      alterations of the hormone level comparing to control groups. We observed
      differences between groups regarding certain cytokines at certain time points.
      Namely: at 72 h of discontinuation IL-2 and IL-4 were elevated in sera of rats
      treated with IMI acutely; at 7d of discontinuation levels of IL-1alpha, IL-5, IL
      10 and IL-12 were affected in both acutely and chronically treated animals.
      Presented data support, regarding some cytokines in serum, the TDS theory.
      Furthermore they refer to important aspect of antidepressants (ADs) action -
      antidepressant discontinuation syndrome (ADS). The most frequently, ADS has been
      described in context of ADs-disrupted monoamine homeostasis. Here, the other
      principle (i.e. immunomodulation) of the syndrome is proposed.

PMID- 29196146
TI  - A non-synaptic mechanism of complex learning: Modulation of intrinsic neuronal
      excitability.
AB  - Training rats in a particularly difficult olfactory discrimination task initiates
      a period of accelerated learning of other odors, manifested as a dramatic
      increase in the rats' capacity to acquire memories for new odors once they have
      learned the first discrimination task, implying that rule learning has taken
      place. At the cellular level, pyramidal neurons in the piriform cortex,
      hippocampus and bsolateral amygdala of olfactory-discrimination trained rats show
      enhanced intrinsic neuronal excitability that lasts for several days after rule
      learning. Such enhanced intrinsic excitability is mediated by long-term reduction
      in the post-burst after-hyperpolarization (AHP) which is generated by repetitive
      spike firing, and is maintained by persistent activation of key second messenger
      systems. Much like late-LTP, the induction of long-term modulation of intrinsic
      excitability is protein synthesis dependent. Learning-induced modulation of
      intrinsic excitability can be bi-directional, pending of the valance of the
      outcome of the learned task. In this review we describe the physiological and
      molecular mechanisms underlying the rule learning-induced long-term enhancement
      in neuronal excitability and discuss the functional significance of such a wide
      spread modulation of the neurons' ability to sustain repetitive spike generation.

PMID- 29196147
TI  - Mast Cells as Drivers of Disease and Therapeutic Targets.
AB  - Mast cells (MCs) contribute to the pathogenesis of a multitude of diseases that
      include MC-driven disorders such as urticaria, type I allergies, and mastocytosis
      as well as autoimmune and other inflammatory disorders and malignant tumors.
      Here, we review and discuss the results of studies that identified and
      characterized how MCs contribute to disease and, importantly, what strategies may
      be used to target MCs and MC effects therapeutically. Specifically, we discuss
      the most common approaches for investigating the role and relevance of MCs in
      various diseases. We also review current therapeutic approaches aimed at
      modulating MC numbers, inhibiting MCs and/or preventing MC activation, modulating
      MC signal transduction and protection from the effects of MC mediators.

PMID- 29196148
TI  - Circulating IL-17-producing mucosal-associated invariant T cells (MAIT) are
      associated with symptoms in children with asthma.
AB  - IL-17 and mucosal-associated invariant T (MAIT) cells have been involved in
      asthma pathogenesis. However, IL-17-producing MAIT cells (MAIT-17) were not
      evidenced. We aimed to determine whether circulating MAIT-17 were detectable in
      children with asthma, and whether they correlated with asthma symptoms or lung
      function. Children from the SPASM cohort of preschoolers with severe wheeze were
      reassessed for asthma at school age, and categorized as exacerbators (1 or more
      severe exacerbations in the previous 12months) or non-exacerbators. Nineteen
      children (10.9years) were included (9 non-exacerbators, 10 exacerbators).
      Circulating MAIT-17 were detected by flow cytometry. Their frequency was higher
      in exacerbators than in non-exacerbators (1.9 [1.01-3.55] vs 0.58 [0.46-1.15],
      p<0.01). MAIT-17 correlated with the number of severe exacerbations (r=0.68,
      p<0.001), and correlated negatively with the ACT score (r=-0.55, p=0.01). In
      summary, MAIT-17 are present in children with asthma and associated with asthma
      symptoms.

PMID- 29196149
TI  - Continuous positive airway pressure treatment with nasal pillows in obstructive
      sleep apnea: long-term effectiveness and adherence.
AB  - BACKGROUNDS: Mask-related side effects can negatively influence adherence to
      continuous positive airway pressure (CPAP). Nasal pillows (P) can be an
      alternative to the standard nasal masks (N), although there are no data about
      their long-term efficacy. This study aimed to assess long-term effectiveness and
      adherence to CPAP therapy delivered with nasal pillows in obstructive sleep apnea
      syndrome (OSAS) patients. METHODS: A retrospective observational design involving
      a series of consecutive CPAP-naive patients affected by OSAS. After an initial
      mask fitting session all patients were allowed to choose the type of nasal
      interface (N or P) they preferred. Outcomes were assessed 5 days after CPAP
      titration, and after 2 and 12 months. Patients were offered the option of
      switching to an alternative mask if needed. RESULTS: Data from 144 patients were
      analyzed. Subjects were predominantly male (76%), middle aged (58.14 +/- 12.86),
      moderately obese (body mass index: 33.89 +/- 7.56), and affected by severe OSAS
      (apnea-hypopnea index: 47.60 +/- 21.31). A total of 102 patients (70.8%) chose P,
      and 42 (29.2%) chose N. Clinical and polygraphic features, and CPAP pressure
      levels were similar in P and N groups, both at baseline and at 12 months. A good
      adherence to treatment was observed in both groups (P, 5.5 +/- 1.8 h; N, 5.3 +/-
      1.5 h). Seventy-six patients (53%) reported at least one side effect during the
      whole study period, without statistically significant between-group differences.
      Nostril pain was the most frequent side effect in P. CONCLUSIONS: Nasal pillows
      showed equal long-term effectiveness and objective adherence as standard nasal
      masks.

PMID- 29196150
TI  - SGLT2 inhibitors with cardiovascular benefits: Transforming clinical care in Type
      2 diabetes mellitus.
AB  - Cardiovascular risk reduction in individuals with Type 2 diabetes mellitus (T2DM)
      is a key part of clinical management. Sodium-glucose co-transporter (SGLT2)
      inhibitors improve glycaemic control, reduce body weight and decrease blood
      pressure. In addition, the SGLT2 inhibitors empagliflozin and canagliflozin
      reduced the risk of composite cardiovascular events in high-risk individuals with
      T2DM in the EMPA-REG OUTCOME trial and the CANVAS Program, respectively.
      Empagliflozin also reduced cardiovascular deaths and improved renal outcomes.
      This class of agents should be considered in people with established
      cardiovascular disease, usually in combination with other glucose lowering
      medications, when satisfactory glycaemic control has not been achieved. The dose
      of insulin or sulfonylureas may need to be lowered when used with SGLT2
      inhibitors, to reduce the risk of hypoglycaemia. Genitourinary infections can
      occur with SGLT2 inhibitors in a small proportion of people. In people with
      osteoporosis or prior amputation, it may be prudent to use empagliflozin rather
      than canagliflozin, based on the increased risk for bone fractures and
      amputations observed with canagliflozin in the CANVAS Program. SGLT2 inhibitors
      have the potential to transform the clinical care of persons with T2DM by not
      only improving glycaemic control but also reducing blood pressure, body weight
      and diabetes-related end-organ complications.

PMID- 29196151
TI  - Effect of vitamin K2 on type 2 diabetes mellitus: A review.
AB  - Type 2 diabetes mellitus (T2DM) continue to be a major public health problem
      around the world that frequently presents with microvascular and macrovascular
      complications. Individuals with T2DM are not only suffering from significant
      emotional and physical misery, but also at increased risk of dying from severe
      complications. In recent years, evidence from prospective observational studies
      and clinical trials has shown T2DM risk reduction with vitamin K2
      supplementation. We thus did an overview of currently available studies to assess
      the effect of vitamin K2 supplementation on insulin sensitivity, glycaemic
      control and reviewed the underlying mechanisms. We proposed that vitamin K2
      improved insulin sensitivity through involvement of vitamin K-dependent-protein
      osteocalcin, anti-inflammatory properties, and lipid-lowering effects. Vitamin K2
      had a better effect than vitamin K1 on T2DM. The interpretation of this review
      will increase comprehension of the development of a therapeutic strategy to
      prevent and treat T2DM.

PMID- 29196152
TI  - Nanotechnology based approaches for anti-diabetic drugs delivery.
AB  - Nanotechnology science has been diverged its application in several fields with
      the advantages to operate with nanometric range of objects. Emerging field of
      nanotechnology has been also being approached and applied in medical biology for
      improved efficacy and safety. Increased success in therapeutic field has focused
      several approaches in the treatment of the common metabolic disorder, diabetes.
      The development of nanocarriers for improved delivery of different oral
      hypoglycemic agents compared to conventional therapies includes nanoparticles
      (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control
      over the increased blood glucose level and thus becoming an eye catching and most
      promising technology now-a-days. Besides, embellishment of nanocarriers with
      several ligands makes it more targeted delivery with the protection of entrapped
      hypoglycaemic agents against degradation, thereby optimizing prolonged blood
      glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the
      aim towards improved diabetes management with minimized risk of acute and chronic
      complications. In this review, we provide an overview on distinctive features of
      each nano-based drug delivery system for diabetic treatment and current NPs
      applications in diabetes management.

PMID- 29196153
TI  - Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus
      IP 174178 in the prevention of bacterial vaginosis recurrence.
AB  - BACKGROUND: Bacterial vaginosis (BV) is a recurrent disease in women despite
      treatment by antibiotics. This study investigated the impact of a vaginal
      probiotic, Lactobacillus crispatus IP174178* (Lc), on the rate of recurrence and
      time to recurrence. METHODS: A prospective, multi-centre, double blind,
      randomised phase III trial in women with at least two documented episodes of BV
      in the previous year (diagnosis confirmed by presence of three Amsel criteria and
      a Nugent score>=7), and who had been clinically cured (i.e., no Amsel criteria)
      after oral metronidazole treatment (1g/day*7 days). The patients were randomised
      to receive vaginal capsules of either Lc or placebo, once a day, for 14 days over
      the first two menstrual cycles and another 14 days of the same treatment for the
      following two menstrual cycles. The primary efficacy endpoint was the number of
      patients with at least one bacteriologically confirmed recurrence of BV. RESULTS:
      Out of 98 assessable patients (mean age 35.7 years), 78 women were evaluated (20
      patients had missing data). During the treatment period, 16/39 patients (41%) had
      at least one recurrence in the placebo group versus 8/39 patients (20.5%) in the
      Lc group (P=0.0497). The time to recurrence was longer by 28% in the Lc group
      (3.75+/-0.16 months) vs. the placebo group (2.93+/-0.18 months) (P=0.0298).
      Tolerability and safety were good in both groups. CONCLUSION: In women with
      recurrent BV after antibiotics, treatment with Lc IP 174178 administered over
      four menstrual cycles, could significantly reduce the rate of recurrence and
      increase the time to recurrence.

PMID- 29196154
TI  - Labour induction practices in France: A population-based declarative survey in 94
      maternity units.
AB  - INTRODUCTION: In 2016, 22.0% of deliveries in France were induced. The current
      lack of high level of evidence data about the methods and indications for
      induction of labour has promoted heterogeneous and non-recommended practices. The
      extent of these different practices is not adequately known in France today,
      although they may influence perinatal outcomes. The objective of this study was
      to report current practices of induction of labour in France. MATERIAL AND
      METHODS: This study surveyed 94 maternity units in seven perinatal networks. A
      questionnaire was sent by email to either the department head or delivery room
      supervisor of these units to ask about their methods for induction and their
      attitudes in specific obstetric situations. RESULTS: The rate of induction varied
      between maternity units from 7.7% to 33% of deliveries. Most units used two
      (39.4%) or three or more (35.1%) agents for cervical ripening. In all, 87 (92.6%)
      units reported using dinoprostone as a vaginal slow-released insert, 59 units
      dinosprostone as a vaginal gel (62.8%) and 46 units a balloon catheter (48.9%).
      Only three units reported using vaginal misoprostol. Inductions without medical
      indication were reported by 71 (75.5%) maternity units, and 22 (23.4%) units even
      when the cervix was unfavourable. Obstetric attitudes in cases of breech
      presentation, previous caesareans, fetal growth restriction or macrosomia and
      prelabour rupture of the membranes varied widely. DISCUSSION: The variability of
      practices for induction of labour and the persistence of disapproved practices
      call for an assessment of the effectiveness and the safety of the different
      strategies.

PMID- 29196155
TI  - Assessment of liver function in pregnant anemic women upon oral iron and folic
      acid supplementation.
AB  - Oral iron therapy is the most widely prescribed treatment for iron deficiency
      anemia. However, oral iron supplementation may also lead to various health
      problems. The recognition of these physiological variations is essential for the
      diagnosis of liver diseases during the course of pregnancy. Therefore, the
      objective of this study was to assess the variations in levels of routine liver
      function tests (LFTs) in pregnant women before and after iron and folic acid
      treatment. Iron and folic acid was supplemented to 500 normal pregnant anemic
      women (mild=200, moderate=200 and severe=100) and 100 age matched normal pregnant
      non-anemic as controls daily for 100 days. Blood index values and liver function
      parameters were precisely monitored. Hemoglobin (Hb), total protein (TP), iron
      (Fe), albumin and alkaline phosphatase (ALP) levels were found increased
      (P<0.001; P<0.01; P<0.05) after treatment in mild, moderate, severe and control,
      respectively. Lipid peroxidation (LPx), aspartate transaminase (AST) and alanine
      transaminase (ALT) were increased in pretreated mild, moderate and severe groups
      and further increased after all treated subjects. Moreover, gamma-glutamyl
      transpeptidase (GGT) was found to decrease in pre and posttreated subjects.
      Treatment with iron and folic acid although has remarkable efficacy for Hb and
      body iron stores although for the cost of increasing the associated compartment
      of total bilirubin, AST and ALT concomitant with decreased GGT levels. Data
      obtained from the present study provide new insights into the mandatory
      application of liver function tests likely to be monitored at regular and
      specific intervals during the course of pregnancy.

PMID- 29196156
TI  - Leiomyomatosis peritonealisis disseminata: Two unusual cases with literature
      review.
AB  - BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is a rare benign
      disease characterized by numerous smooth muscle-like cell nodules disseminated
      among the abdominal cavity. The pathogenesis of LPD is not well-known; one
      hypothesis, widely reported, is parasitic LPD (after uterine myoma surgery). The
      role of hormonal status has been raised without any evidence yet confirmed.
      Lesions of LPD can mimic carcinomatosis and lead to an inappropriate treatment.
      Total and spontaneous regression of the nodules is sometimes reported. This
      benign disease is also associated with leiomyosarcoma or invasive lesions,
      leading to mechanical complication or death. CASES AND REVIEW: We report two
      additional cases. The first case occurred in a 78-year-old woman with a history
      of total hysterectomy for uterine myoma, and was revealed by a small bowel
      obstruction. Second case occurred in a 50-year-old non-menopausal woman suffering
      from obesity (BMI 61,7), with an incidental diagnostic of LPD during a surgical
      procedure and spontaneous full regression of the disease. We analyzed 165
      articles. We fond 16 menopausal women with LPD, 5 patients with intestinal
      obstruction or peritonitis due to LPD and 5 cases with spontaneous regression of
      LPD lesions. Six cases of recurrence as leiomyosarcoma were found. CONCLUSION:
      Cases of LPD have been reported without uterine myoma history and could be from
      extrauterine origin. Hysterectomy and oophorectomy should not be performed in
      first line. Peritoneal cytology should be done in case of ascites. Recurrences as
      leiomyosarcoma are reported and occurs early and justify a close follow up the
      first years.

PMID- 29196157
TI  - Laparoscopic pelvic lymphadenectomy in patients with intermediate-risk
      endometrial cancer: Is it worth it?
AB  - OBJECTIVE: The main aim of this study is to evaluate operative and postoperative
      morbidity of laparoscopic pelvic lymphadenectomy as well as its potential impact
      on the postoperative management in patients with an intermediate-risk of
      endometrial cancer. METHODS: We did a retrospective study between January 2009
      and December 2013. We included all patients operated by laparoscopy for
      endometrial cancer presumed to have an intermediate-risk of recurrence. Pelvic
      lymphadenectomy in this group of patients was performed at the discretion of
      operating surgeons. Patients were consequently divided into two groups according
      to whether or not pelvic lymphadenectomy was performed. We made a comparative
      analysis between these two groups. RESULTS: Overall, 116 patients were managed
      for endometrial cancer presumed to be intermediate-risk. Among these, 93 received
      treatment with laparoscopy and were included in the study. Patients'
      characteristics did not differ between the two groups. The mean duration of
      surgery was significantly longer when pelvic lymphadenectomy was performed. The
      average number of retrieved lymph nodes was 13 and we had seven patients with
      positive lymph nodes (10%). CONCLUSION: Pelvic lymphadenectomy allows a better
      postoperative classification for some patients without more complication.

PMID- 29196158
TI  - Prevalence of cholesteryl ester storage disease among hypercholesterolemic
      subjects and functional characterization of mutations in the lysosomal acid
      lipase gene.
AB  - Lysosomal acid lipase hydrolyzes cholesteryl esters and triglycerides contained
      in low density lipoprotein. Patients who are homozygous or compound heterozygous
      for mutations in the lysosomal acid lipase gene (LIPA), and have some residual
      enzymatic activity, have cholesteryl ester storage disease. One of the clinical
      features of this disease is hypercholesterolemia. Thus, patients with
      hypercholesterolemia who do not carry a mutation as a cause of autosomal dominant
      hypercholesterolemia, may actually have cholesteryl ester storage disease. In
      this study we have performed DNA sequencing of LIPA in 3027 hypercholesterolemic
      patients who did not carry a mutation as a cause of autosomal dominant
      hypercholesterolemia. Functional analyses of possibly pathogenic mutations and of
      all mutations in LIPA listed in The Human Genome Mutation Database were performed
      to determine the pathogenicity of these mutations. For these studies, HeLa T-REx
      cells were transiently transfected with mutant LIPA plasmids and Western blot
      analysis of cell lysates was performed to determine if the mutants were
      synthesized in a normal fashion. The enzymatic activity of the mutants was
      determined in lysates of the transfected cells using 4-methylumbelliferone
      palmitate as the substrate. A total of 41 mutations in LIPA were studied, of
      which 32 mutations were considered pathogenic by having an enzymatic activity
      <10% of normal. However, none of the 3027 hypercholesterolemic patients were
      homozygous or compound heterozygous for a pathogenic mutation. Thus, cholesteryl
      ester storage disease must be a very rare cause of hypercholesterolemia in
      Norway.

PMID- 29196160
TI  - Quantitative functional evaluation of a 3D-printed silicone-embedded prosthesis
      for partial hand amputation: A case report.
AB  - STUDY DESIGN: A male patient with partial hand amputation of his nondominant
      hand, with only stumps of the proximal phalanx of the first and fifth finger, was
      evaluated. The performance of using two alternative 3D printed silicone-embedded
      personalized prostheses was evaluated using the quantitative Jebsen Hand Function
      Test. INTRODUCTION: Custom design and fabrication of 3D printed prostheses
      appears to be a good technique for improving the clinical treatment of patients
      with partial hand amputations. Despite its importance the literature shows an
      absence of studies reporting on quantitative functional evaluations of 3D printed
      hand prostheses. PURPOSE OF THE STUDY: We aim at producing the first quantitative
      assessment of the impact of using 3D printed silicone-embedded prostheses that
      can be fabricated and customized within the clinical environment. METHODS:
      Alginate molds and computed tomographic scans were taken from the patient's hand.
      Each candidate prosthesis was modeled in Computer Aided Design software and then
      fabricated using a combination of 3D printed parts and silicone-embedded
      components. DISCUSSION: Incorporating the patient's feedback during the design
      loop was very important for obtaining a good aid on his work activities. Although
      the explored patient-centered design process still requires a multidisciplinary
      team, functional benefits are large. CONCLUSION(S): Quantitative data
      demonstrates better hand performance when using 3D printed silicone-embedded
      prosthesis vs not using any aid. The patient accomplished complex tasks such as
      driving a nail and opening plastic bags. This was impossible without the aid of
      produced prosthesis.

PMID- 29196161
TI  - Effects of trapezius kinesio taping on scapular kinematics and associated
      muscular activation in subjects with scapular dyskinesis.
AB  - STUDY DESIGN: Crossover repeated-measure design. INTRODUCTION: Scapular
      dyskinesis rehabilitation programs that focus on inhibiting upper trapezius (UT)
      and activating the lower trapezius (LT) may assist in restoring scapular
      movements. We hypothesized that taping may be able to normalize scapular
      movements and associated muscular recruitment. PURPOSE OF THE STUDY: The purpose
      of this study was to investigate the immediate effects of kinesio taping over
      trapezius on scapular kinematics and muscular activation in different dyskinesis
      patterns. We expected that taping can improve scapular kinematics and muscular
      activation in subjects with dyskinesis. METHODS: Fifty-four participants with
      inferior angle prominence (pattern I), medial border prominence (pattern II), and
      mixed pattern (pattern I + II) were recruited. Kinesio taping was applied over 3
      parts of trapezius muscles, including UT, middle trapezius (MT), and LT. The
      scapular kinematics and electromyographic data of trapezius and serratus anterior
      were collected during scapular plane elevation without taping and after each
      taping application. RESULTS: UT taping decreased UT activity (5%-7%; P = .001
      .003) in 72% of participants with pattern II and pattern I + II dyskinesis, with
      increased posterior tipping (2.2 degrees -2.5 degrees ; P = .003) in pattern II
      dyskinesis. MT taping increased UT activity (3%; P = .003) in 48% of participants
      with pattern II dyskinesis. DISCUSSION: The taping over the trapezius muscle may
      help to restore coordinated scapular muscle balance and increased upward rotation
      of the scapula, especially in pattern II dyskinesis. Although no electromyography
      or kinematic difference was found with LT taping in each dyskinesis pattern,
      methods of applying LT taping need to be further investigated. CONCLUSION:
      Reduced UT muscle activity and scapular posterior tipping are appropriate when
      applying taping over UT muscle in patterns II and I + II dyskinesis. Caution
      should be taken when applying taping over MT and LT muscles in terms of increased
      UT activity, especially in pattern II dyskinesis.

PMID- 29196159
TI  - Cholesterol trafficking and raft-like membrane domain composition mediate
      scavenger receptor class B type 1-dependent lipid sensing in intestinal
      epithelial cells.
AB  - Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In
      intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR
      B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction
      of its C-terminal transmembrane domain with plasma membrane cholesterol. To
      clarify the initiating events occurring during lipid sensing by SR-B1, we
      analyzed cholesterol trafficking and raft-like domain composition in intestinal
      epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A,
      defective in membrane cholesterol binding and signal initiation. These features
      of SR-B1 were found to influence both apical cholesterol efflux and intracellular
      cholesterol trafficking from plasma membrane to lipid droplets, and the lipid
      composition of raft-like domains. Lipidomic analysis revealed likely
      participation of d18:0/16:0 sphingomyelin and 16:0/0:0
      lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis
      identified proteins, whose abundance changed in raft-like domains during lipid
      sensing, and these included molecules linked to lipid raft dynamics and signal
      transduction. These findings provide new insights into the role of SR-B1 in
      cellular cholesterol homeostasis and suggest molecular links between SR-B1
      dependent lipid sensing and cell cholesterol and lipid droplet dynamics.

PMID- 29196162
TI  - Isolation of mammalian stress granule cores for RNA-Seq analysis.
AB  - Stress granules are dynamic, conserved non-translating RNA-protein assemblies
      that form during cellular stress and are related to pathological aggregates in
      many neurodegenerative diseases. Mammalian stress granules contain stable
      structures, referred to as "cores" that can be biochemically purified. Herein, we
      describe a step-by-step guide on how to isolate RNA from stress granule cores for
      RNA-Seq analysis. We also describe a methodology for validating the RNA-Seq
      results by single molecule FISH and how to quantify the single molecule FISH
      results. These protocols provide a starting point for describing the RNA content
      of stress granules and may assist in the discovery of the assembly mechanisms and
      functions of stress granules in a variety of biological contexts.

PMID- 29196163
TI  - The miR-182/SORT1 axis regulates vascular smooth muscle cell calcification in
      vitro and in vivo.
AB  - Arterial calcification is a common feature of cardiovascular disease. Sortilin is
      involved in the development of atherosclerosis, but the specific mechanism is
      unclear. In this study, we established calcification models in vivo and in vitro
      by using vitamin D3 and beta-glycerophosphate, respectively. In vivo, the
      expression of SORT1 was up-regulated and the expression of miR-182 was down
      regulated in calcified arterial tissues. Meanwhile there was a negative
      correlation between SORT1 expression and miR-182 levels. In vitro, downregulating
      SORT1 expression using shRNA inhibited beta-glycerophosphoric induced vascular
      smooth muscle cells (VSMCs) calcification. Moreover, reduced sortilin levels
      followed transfection of miR-182 mimics, whereas there was a significant increase
      in sortilin levels after transfection of miR-182 inhibitors. A luciferase
      reporter assay confirmed that SORT1 is the direct target of miR-182. Our study
      suggests that SORT1 plays a vital role in the development of arterial
      calcification and is regulated by miR-182.

PMID- 29196165
TI  - Osteopontin promotes collagen I synthesis in hepatic stellate cells by miRNA-129
      5p inhibition.
AB  - Activation of hepatic stellate cells (HSCs) is an essential event in the
      initiation and progression of liver fibrosis. HSCs are believed to be the major
      source of collagen-producing myofibroblasts in fibrotic livers. A key feature in
      the pathogenesis of liver fibrosis is fibrillar Collagen I (Col 1) deposition.
      Osteopontin (OPN), an extracellular matrix (ECM) cytokine expressed in HSCs,
      could drive fibrogenesis by modulating the HSC pro-fibrogenic phenotype and Col 1
      expression. Here, we aimed to investigate the molecular mechanism of OPN
      regulating the activation of HSCs. Our results showed that hepatic expression of
      OPN was increased in patients with liver fibrosis. In addition, hepatic OPN was
      positively correlated with Col 1 and alpha-SMA. Recombinant OPN (rOPN)
      upregulated Col 1 and alpha-SMA expression in LX-2 cells. However, OPN knockdown
      downregulated Col 1 expression. The 3'-UTR of the collagen 1 (Col 1) was
      identified to bind miR-129-5p. Transfection of miR-129-5p mimic in HSC resulted
      in a marked reduction of Col 1 expression. Conversely, a decrease in miR-129-5p
      in HSCs transfected by anti-sense miR-129-5p (AS-miR-129-5p) caused Col 1
      upregulation. Furthermore, luciferase reporter assay showed that miR-129-5p
      directly target the 3'-UTR of Col1alpha1 mRNA via repressing its post
      transcriptional activities. Finally, miR-129-5p level was decreased in fibrotic
      liver of human, and reduced by rOPN treatment. In contrast, miR-129-5p was
      induced in HSCs transfected by OPN siRNA. These data suggested that OPN induces
      Col 1 expression via suppression of miR-129-5p in HSCs.

PMID- 29196164
TI  - Glucocorticoids indirectly decrease colon cancer cell proliferation and invasion
      via effects on cancer-associated fibroblasts.
AB  - Cancer-associated fibroblasts (CAFs) support cancer growth, invasion, and
      metastasis. Glucocorticoids (GCs), drugs often administered together with
      chemotherapy, are steroidal ligands of the glucocorticoid receptor (GR), a
      transcription factor which upon activation regulates expression of multiple genes
      involved in suppression of inflammation. We have previously shown that in
      dexamethasone (Dex)-treated CAFs derived from colon cancer, production and
      secretion of several factors related to cancer progression, such as tenascin C
      (TNC) and hepatocyte growth factor (HGF), were strongly suppressed. In this study
      we show that GCs can neutralize the cancer cell-promoting properties of CAFs.
      Conditioned medium from solvent-treated CAFs (CMCTRL) stimulates proliferation,
      motility and stretched morphotype of GR-deficient HCT8/E11 colon cancer cells.
      Yet, HCT8/E11 proliferation and stretched morphotype are impaired upon treatment
      with conditioned medium from Dex-treated CAFs (CMDEX), but HCT8/E11 cell
      migration is slightly increased under these conditions. Moreover, expression and
      potential activity of MMP-2 is also reduced in CMDEX compared with CMCTRL. These
      combined in vitro results concur with the results from in vivo chick
      chorioallantoic membrane assays, where the co-cultures of CAFs with colon cancer
      cells displayed impaired tumor formation and cancer cell invasion due to Dex
      administration. Combined, GC treatment influences cancer cell behavior indirectly
      through effects on CAFs.

PMID- 29196166
TI  - 1,25(OH)2D3 attenuates pulmonary arterial hypertension via microRNA-204 mediated
      Tgfbr2/Smad signaling.
AB  - Pulmonary arterial hypertension (PAH) is a devastating disease characterized by
      high pulmonary artery pressure. It is reported that microRNA-204 (miR-204) plays
      an important role in the development of PAH. Calcitriol [1,25-dihydroxyvitamin
      D3, 1,25(OH)2D3] mediates multiple pathophysiological processes. The aim of the
      current study was to explore the role of 1,25(OH)2D3 in PAH. PAH was induced in
      rats and rat pulmonary arterial endothelial cells (PAECs) were isolated as in
      vitro PAH model. The mean pulmonary artery pressure, morphologic changes, and
      expressions of transforming growth factor-beta1 (Tgfbr2), Smad2/7, alpha smooth
      muscle actin (alpha-SMA), and p21 were then measured. Furthermore, the effect of
      1,25(OH)2D3 on rat PAECs with or without hypoxia treatment was also assessed by
      measuring the proliferation, migration, and cell cycle distribution of PAECs. The
      potential targets of miR-204 were also predicted and validated with a dual
      luciferase reporter system. Then the role of miR-204 and Tgfbr2 in the anti-PAH
      effect of 1,25(OH)2D3 was further explored by modulating the expression of the
      two genes. The overall pulmonary hypertension and hypoxia-induced proliferation
      and migration of PAECs were attenuated by administration of 1,25(OH)2D3, which
      was associated with the suppressed expressions of Tgfbr2, alpha-SMA, and Smad7
      and induced expressions of miR-204, p21 and Smad2 both in vitro and in vivo.
      Moreover, the luciferase reporter assay identified Tgfbr2 as a novel direct
      target of miR-204. Both overexpression of miR-204 and inhibition of Tgfbr2 would
      strengthen the effect of 1,25(OH)2D3 administration. Findings outlined in the
      current study demonstrated that 1,25(OH)2D3 was a promising therapeutic modality
      for treatment of PAH, function of which was exerted through miR-204 mediated
      Tgfbr2 signaling.

PMID- 29196167
TI  - Cathepsin B links oxidative stress to the activation of NLRP3 inflammasome.
AB  - Oxidative stress-mediated activation of NLRP3 inflammasome in microglia is
      critical in the development of neurodegerative diseases such as Alzheimer's
      disease (AD), Parkinson disease (PD). However, the mechanism underlying oxidative
      stress activates NLRP3 inflammasome remains exclusive. Here we demonstrated
      cathepsin B (CTSB) as a regulator of the activation of NLRP3 inflammasome by
      H2O2.H2O2 induced IL-1beta secretion in NLRP3 inflammasome-dependent manner.H2O2
      treatment increased CTSB activity, which in turn activated NLRP3 inflammasome,
      and subsequently processed pro-caspase-1 cleavage into caspase-1, resulting in IL
      1 beta secretion. Genetic inhibition or pharmacological inhibition of CTSB
      blocked the cleavage of pro-caspase-1 into caspase-1 and subsequent IL-1 beta
      secretion induced by H2O2. Importantly, CTSB activity, IL-1beta levels and
      malondialdehyde (MDA) were remarkably elevated in plasma of AD patients compared
      to healthy controls, while glutathione was significantly lower than healthy
      controls. Correlation analyses showed that CTSB activity was positively
      correlated with IL-1beta and MDA levels, but negatively correlated with GSH
      levels in plasma of AD patients. Taken together, our results indicate that
      oxidative stress activates NLRP3 through upregulating CTSB activity. Our results
      identify an important biological function of CTSB in neuroinflammation,
      suggesting that CTSB is a potential target in AD therapy.

PMID- 29196168
TI  - Microscopic cuticle structure comparison of pupal melanic and wild strain of
      Spodoptera exigua and their gene expression profiles in three time points.
AB  - The beet armyworm, Spodoptera exigua (Hubner), is one of the major crop pests and
      is a target for current pest control approaches using insecticides. S. exigua
      melanic mutants (SEM) spontaneously occurred in the S. exigua wild type (SEW)
      strain and have been maintained under laboratory conditions on an artificial
      diet. Scanning electron microscopy showed that the inner cuticle of the SEM had a
      denser and less orderly structure. We investigated the cuticle protein genes
      using RNA-seq at three different developmental stages of both SEM and SEW.
      Comparison of cDNA libraries showed that 7257 CPs were significantly up-regulated
      and 664 genes were significantly downregulated in SEM at the developmental stage
      of 46-h in the fifth instar. In addition, 460 genes were significantly up
      regulated and 439 genes were significantly down-regulated in the SEM at the
      development stage of 4-h before pupation. Moreover, 162 genes were significantly
      up-regulated and 293 genes were significantly downregulated in the SEM, just
      after pupation. Two genes CPR63 and CPR97 were identified from RNA sequences to
      verify the differentially expressed gene (DEG) results through quantitative real
      time PCR (qRT-PCR). The results show that expression of both CPR63 and CPR97
      structural cuticular proteins were significantly different between SEM and SEW.
      This functional analysis may help in understanding the role that these genes play
      in the cuticle pattern of the SEM.

PMID- 29196169
TI  - Purinergic system displays an anti-inflammatory profile in serum of silver
      catfish experimentally infected with Streptococcus agalactiae: An attempt to
      ameliorate the inflammatory response.
AB  - The purinergic system is recognized to modulate extracellular adenosine
      triphosphate (ATP) and related nucleotides through the activities of triphosphate
      diphosphohydrolase (NTPDase), 5'-nucleotidase, and adenosine deaminase (ADA),
      thereby playing an essential role in the immunoregulation of inflammatory and
      immune responses. Thus, the aim of this study was to evaluate whether the
      purinergic system can improve the inflammatory response in fish experimentally
      infected with Streptococcus agalactiae through the modulation of seric NTPDase,
      5'-nucleotidase and ADA activities. Seric NTPDase (ATP as substrate) and 5'
      nucleotidase activities increased in silver catfish experimentally infected with
      S. agalactiae compared with the uninfected control group, while seric ADA
      activity decreased. Based on this evidence, our findings suggest that regulation
      of adenine nucleotide hydrolysis occurs in an attempt to restrict the
      inflammatory process and improve the immune system by hydrolyzing excess
      extracellular ATP. On the other hand, downregulation of seric ADA activity may be
      an attempt to augment extracellular adenosine (a molecule with anti-inflammatory
      effects) levels. In summary, the purinergic system is capable of modulating the
      immune and inflammatory responses during fish streptococcosis.

PMID- 29196170
TI  - Evaluation of phytochemical analysis and antimicrobial activities Allium
      essential oil against the growth of some microbial pathogens.
AB  - In this experimental study, the Allium essential oil (AHEO) was extracted through
      the hydrodistillation method. AHEO components were identified through gas
      chromatography/mass spectrometry (GC/MS), and its antioxidant properties and
      total phenolic content were examined through the methods of 2,2-diphenyl-1
      picrylhydrazyl (DPPH), beta-carotene/linoleic acid inhibition and Folin
      Ciocalteu, respectively. The antimicrobial effect of AHEO was evaluated on
      Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Bacillus subtilis,
      Staphylococcus aureus, Streptococcus pyogenes, and Candida albicans through the
      methods of well diffusion, disk diffusion, minimum inhibitory concentration, and
      minimum bactericidal/fungicidal concentration. Phytochemical constituents
      (alkaloids, tannins, saponins, flavone and glycosides) were evaluated. 5
      chloroorcylaldehyde with a percentage of 45.6% was the major compound of AHEO.
      Increasing concentration of AHEO had a significant effect (p <= 0.05) on
      inhibition zone diameter. The MICs of the AHEO varied from 0.25 mg/ml to 2 mg/ml.
      The MBCs/MFCs of the AHEO varied from 0.25 mg/ml to 4 mg/ml. The results of
      phytochemical screening of AHEO showed the existence of alkaloids, tannins,
      saponins, flavone and glycosides. There was also little difference between disk
      diffusion and well diffusion methods, and the data was well distributed
      throughout the X and Y components.

PMID- 29196172
TI  - In silico identification and construction of microbial gene clusters associated
      with biodegradation of xenobiotic compounds.
AB  - Chemical substances not showing any importance in existence of biological systems
      and causing serious health hazards may be designated as Xenobiotic compound.
      Elimination or degradation of these unwanted substances is a major issue of
      concern for current time research. Process of biodegradation is a very important
      aspect of current research as discussed in current manuscript. Current study
      focuses on the detailed mining of data for the construction of microbial
      consortia for wide range of xenobiotics compounds. Intensive literature search
      was done for the construction of this library. Desired data was retrieved from
      NCBI in fasta format. Data was analysed through homology approaches by using
      BLAST. This homology based searched enriched with a great vision that not only
      bacterial population but many other cheap and potential sources are available for
      different xenobiotic degradation. Though it was focused that bacterial population
      covers a major part of biodegradation which is near about 90.6% but algae and
      fungi are also showing promising future in degradation of some important
      xenobiotic compounds. Analysis of data reveals that Pseudomonas putida has
      potential for degrading maximum compounds. Establishment of correlation through
      cluster analysis signifies that Pseudomonas putida, Aspergillus niger and
      Skeletonema costatum can have combined traits that can be used in finding out
      actual evolutionary relationship between these species. These findings may also
      givea new outcome in terms of much cheaper and eco-friendly source in the area of
      biodegradation of specified xenobiotic compounds.

PMID- 29196171
TI  - Nano silver particle synthesis using Swertia paniculata herbal extract and its
      antimicrobial activity.
AB  - In the present study, green synthesis of silver nanoparticles (AgNPs) is
      demonstrated using medicinal herb Swertia paniculata extract. The plant extract
      acted both as reducing and capping agents during synthesis process, where silver
      nitrate was used as silver source. Subsequent analysis revealed that particles
      had size range between 31 and 44 nm and were spherical in shape. Among reaction
      parameters, temperature and time had significantly influenced the synthesis
      reaction. Also, synthesized nanoparticles were found stable up to 90 days.
      Further, antimicrobial activity against gram negative and gram positive bacterial
      strains was done and results showed that synthesized AgNPs had better
      antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae
      under standard incubation conditions. Study shows that these particles can be
      very promising in biomedical applications in future.

PMID- 29196173
TI  - Characterization of pathogenic roles of two Erysipelothrix rhusiopathiae surface
      proteins.
AB  - Erysipelothrix rhusiopathiae is the causative agent of animal erysipelas and
      human erysipeloid. E. rhusiopathiae HP0728 and HP1472 have been reported to be
      down regulated in low-virulence or avirulent strains, but their pathogenic roles
      are not known. In this study, it was found that E. rhusiopathiae HP0728 and
      HP1472 were displayed on the surface of E. rhusiopathiae. Moreover, recombinant
      HP1472 could adhere to pig vascular endothelial cells. Recombinant HP0728 could
      bind host plasminogen but could not bind fibronectin. In conclusion, our work
      suggested that HP0728 and HP1472 are virulence factors of E. rhusiopathiae.

PMID- 29196174
TI  - The prevalence and drug resistance pattern of extended spectrum beta-lactamases
      (ESBLs) producing Enterobacteriaceae in Africa.
AB  - Extended spectrum beta-lactamases (ESBLs) are a group of enzymes that can
      hydrolyze a variety of beta-lactams including fourth generation cephalosporins
      and compromise the efficacy of all beta-lactams, except cephamycins and
      carbapenems. In the worldwide, the ESBL group of enzymes are found widely and
      causes a severe infection on human health which leads to various diseases. This
      review primarily focusses on analyzing the prevalence and drug resistance
      patterns in the African continent. From the earlier reported data shown only the
      minimal amount of surveillance information's has been summarized with respect to
      antimicrobial resistance on ESBLs producing Enterobacteriaceae both in hospital
      and community settings. To bring the present scenario in limelight, the present
      study explores the prevalence of ESBL-producing Enterobacteriaceae in various
      countries in Africa and specifically, to identify most common ESBL genes in
      hospital and community. The observation was initiated with the exhaustive
      literature search using PubMed and other databases to broaden the study from the
      earlier investigations in the African countries concerned about the prevalence
      rate of ESBL producing Enterobacteriaceae. Further, this study was extended to
      review various hypothesis of the hydrolytic mechanism, which was detailed by
      several authors performed earlier through computational approaches.
      Interestingly, the ESBLs class A and D were found to be common classes in Africa,
      with the gene CTX-M-15 being most prevalent. Notably, the present review
      highlights the prevalence on individual countries in Africa and it is extremely
      significant to prevent the dissemination of ESBL-producing Enterobacteriaceaea.
      Hence, this review on surveillance will be the benchmark to enhance the research
      on antimicrobial resistance patterns for all classes and genes. Furthermore,
      explored in-sights in this paper will be helpful for the further investigations
      to develop quicker, cost effective, and reliable diagnostic strategies and new
      effective therapies.

PMID- 29196175
TI  - Anti-tubercular and probiotic properties of coagulase-negative staphylococci
      isolated from Koozh, a traditional fermented food of South India.
AB  - In the last few years, the demand for the tremendous therapeutic applications of
      indigenous probiotic bacteria from diversified fermented food products has
      surged. In view of this, the present study was documented to evaluate the anti
      tubercular and probiotic properties of coagulase-negative staphylococci (CNS)
      indigenous to Koozh, a traditional fermented food product of South India. A total
      of 18 isolates were purified from Koozh, and tested for anti-tubercular activity
      against Mycobacterium tuberculosis H37Rv using luciferase reporter phage (LRP)
      assay. Among them, six isolates revealed higher percentage (>90%) of relative
      light unit (RLU) reduction. These six isolates were further evaluated for their
      in vitro probiotic attributes using standard protocols. All six staphylococci
      strains disclosed good probiotic properties. Moreover, Staphylococcus hominis
      strain MANF2 showed high cell survival percentage (92.2%) at pH 2.0 as well as
      towards simulated gastric juice (88.51%). Furthermore, strain MANF2 was found to
      be resistant to bile salt after 24 h of incubation with maximal viability of 5.71
      +/- 0.02 log cfu/mL, and depicted the deconjugation of bile salt as well. All the
      isolates exhibited strong auto-aggregation capacity (44.4 +/- 1.2-68.1 +/- 1.5%),
      and hydrophobicity against toluene (55.0 +/- 1.2-72.0 +/- 1.1%). Additionally,
      strain MANF2 was observed to be highly resistant to phenol (6.27 +/- 0.01 log
      cfu/mL) and lysozyme (81.1 +/- 1.6% viability). Most importantly, all six
      isolates depicted good hypocholesterolemic effect, slight beta-galactosidase
      activity, and moderate proteolytic property. The strains were sensitive to all
      the tested conventional antibiotics, except Nalidixic acid. In addition to this,
      all staphylococci strains demonstrated significant DPPH (2,2-Diphenyl-1
      picrylhydrazyl) scavenging, hydrogen peroxide tolerance, and hydroxyl radical
      scavenging activity in a dose dependent manner, thereby exhibiting the potent
      antioxidative properties of isolates. The negative results obtained from
      haemolytic, DNase, and gelatinase tests revealed the non-pathogenicity and safety
      aspect of these strains. In a nutshell, the present investigation divulges the
      persuasive anti-tubercular and probiotic properties of staphylococci,
      particularly strain MANF2, and recommended the further exploitation of Koozh
      associated CNS in pharmaceutics.

PMID- 29196176
TI  - Assessing value in breast reconstruction: A systematic review of cost
      effectiveness studies.
AB  - INTRODUCTION: Breast reconstruction is one of the most common procedures
      performed by plastic surgeons and is achieved through various choices in both
      technology and method. Cost-effectiveness analyses are increasingly important in
      assessing differences in value between treatment options, which is relevant in a
      world of confined resources. A thorough evaluation of the cost-effectiveness
      literature can assist surgeons and health systems evaluate high-value care
      models. METHODS: A systematic review of PubMed, Web of Science, and the Cost
      Effectiveness Analysis Registry was conducted. Two reviewers independently
      evaluated all publications up until August 17, 2017. RESULTS: After removal of
      duplicates, 1996 records were screened, from which 53 studies underwent full text
      review. All the 13 studies included for final analysis mention an incremental
      cost-effectiveness ratio. Five studies evaluated the cost-effectiveness of
      technologies including acellular dermal matrix (ADM) in staged prosthetic
      reconstruction, ADM in direct-to-implant (DTI) reconstruction, preoperative
      computed tomography angiography in autologous reconstruction, indocyanine green
      dye angiography in evaluating anastomotic patency, and abdominal mesh
      reinforcement in abdominal tissue transfer. The remaining eight studies evaluated
      the cost-effectiveness of different reconstruction methods. Cost-effective
      strategies included free vs. pedicled abdominal tissue transfer, DTI vs. staged
      prosthetic reconstruction, and fascia-sparing variants of free abdominal tissue
      transfer. CONCLUSIONS: Current evidence demonstrates multiple cost-effective
      technologies and methods in accomplishing successful breast reconstruction.
      Plastic surgeons should be well informed of such economic models when engaging
      payers and policymakers in discussions regarding high-value breast
      reconstruction.

PMID- 29196177
TI  - Muscarinic receptors in the nucleus accumbens shell play different roles in
      context-induced or morphine-challenged expression of behavioral sensitization in
      rats.
AB  - Both drug-related cues and drug priming are the main factors that induce relapse
      of drug addiction. Previous research has reported that blockade of the muscarinic
      receptors could significantly depress addictive behavior, suggesting that the
      muscarinic receptors might be involved in drug use and relapse behavior. The
      nucleus accumbens (NAc), especially the shell of the NAc, where the muscarinic
      receptors are expressed, is critical for craving and relapse. This study
      investigated the effects of microinfusion of the muscarinic receptor antagonist
      scopolamine into the NAc shell on context- and morphine-induced expression of
      behavioral sensitization. Behavioral sensitization was established by exposure to
      5mg/kg morphine once daily for five consecutive days. Expression of behavioral
      sensitization was induced by saline challenge or 5mg/kg morphine challenge. The
      results showed that: (a) the muscarinic receptor antagonist scopolamine
      (10.8MUg/rat) microinjected into the NAc shell blocked expression of conditional
      sensitization; (b) acetylcholinesterase inhibitor huperzine-A (0.5 and
      0.1MUg/rat), but not scopolamine (10.8MUg/rat), microinjected into the NAc shell
      blocked morphine-induced expression of sensitization; and (c) pre-infusion of
      scopolamine (10.8MUg/rat) reversed the inhibitory effect of huperzine-A
      (0.5MUg/rat) on morphine-induced sensitization. Our findings suggest that
      muscarinic receptors in the NAc shell play different roles in context-induced and
      morphine-challenged expression of behavioral sensitization.

PMID- 29196179
TI  - Urethral recurrence after radical cystectomy for urothelial carcinoma: A
      systematic review and meta-analysis.
AB  - PURPOSE: Currently, identified factors for urethral recurrence (UR) are based on
      individual reporting which has displayed controversy. In addition, risk of UR is
      one of the limiting factors to offer neobladder diversion during radical
      cystectomy (RC). We aim to systematically evaluate the incidence and risk factors
      of UR post-RC and its effect on survival. MATERIALS AND METHODS: A systematic
      online search was conducted according to PRISMA statement for publications
      reporting on UR after RC. From initial 802 results, 14 articles including 6169
      patients were included finally after exclusion of ineligible studies. RESULTS:
      The incidence rate of UR was 4.4% (1.3%-13.7%). It was significantly lower with
      neobladder diversion (odds ratio = 0.44, 95% CI: 0.24-0.79, P = 0.006). Muscle
      invasion (hazard ratio = 1.18, 95% CI: 0.86-1.62, P = 0.31), carcinoma in situ
      (hazard ratio 0.97, 95% CI: 0.64-1.47, P = 0.88), prostatic stromal involvement
      (hazard ratio = 2.26, 95% CI: 0.01-627.75, P = 0.78), and prostatic urethral
      involvement (hazard ratio = 2.04, 95% CI: 0.20-20.80, P = 0.55) have no
      significant effect on UR. Men displayed tendency toward higher incidence of UR
      (odds ratio = 2.21, 95% CI: 0.96-5.06, P = 0.06). Absence of recurrence displayed
      tendency toward better disease specific survival, yet not significant (hazard
      ratio = 0.84, 95% CI: 0.66-1.08, P = 0.17). These results are limited by the
      retrospective nature of the included studies. CONCLUSION: Muscle invasion,
      carcinoma in situ and prostatic stromal or urethral involvement at time of RC
      have no significant effect on UR. Orthotopic neobladder is associated with a
      significant lower risk of UR after RC.

PMID- 29196178
TI  - Long-Term Remissions of Patients With Follicular Lymphoma Grade 3 Treated With R
      CHOP.
AB  - BACKGROUND: The optimal management of patients with follicular lymphoma Grade 3
      (FLG3) is controversial. PATIENTS AND METHODS: This is a case series of 45
      patients with FLG3 treated with first-line R-CHOP (rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisone) and observed for an extended time
      interval. RESULTS: The overall response rate was 100% and the median progression
      free survival (PFS) has not been reached, with a 3-year PFS of 70%; 14 (31%)
      patients relapsed, nearly all within 3 years. The baseline characteristic more
      strongly associated with a shorter PFS were lymph >4 node sites and presence of B
      symptoms. Three patients later progressed to diffuse large B cell lymphoma, all
      had baseline elevated serum lactate dehydrogenase level and high International
      Prognostic Index score. Median overall survival has not been reached. All 4
      patients who later developed acute myeloid leukemia were older than 60 years at
      the time of start of therapy. CONCLUSION: R-CHOP is an effective first-line
      treatment for patients with FLG3, and might provide extended PFS, comparable with
      outcomes observed in diffuse large B-cell lymphoma, particularly in subgroups
      with limited nodal disease.

PMID- 29196180
TI  - Unraveling the cell-type dependent radiosensitizing effects of gold through the
      development of a multifunctional gold nanoparticle.
AB  - The radiosensitizing efficacy of gold is well established, however, there remain
      several significant barriers to the successful clinical translation of nano-sized
      gold particles (AuNPs). These barriers include: retaining stability in relevant
      biological sera, demonstrating effectiveness at clinically relevant AuNP
      concentrations and identifying the biological context where significant benefit
      is most likely to be achieved. Herein we have developed a AuNP preparation,
      stress-tested to provide effective protection from salt and serum mediated
      agglomeration. Furthermore, the core AuNP is co-functionalized with two
      biologically derived peptides designed to enhance endocytosis and promote
      endosomal escape, thus maximizing intracellular AuNP surface area. In summary,
      these investigations demonstrate restored AuNP internalization using the co
      functionalized preparation that generated significant radiosensitization, in both
      in vitro and in vivo models, at clinically viable treatment concentrations.
      Furthermore, we have identified an underpinning biological mechanism in the
      inherent radical scavenging capacity that could be used to predict
      radiosensitizing efficacy.

PMID- 29196181
TI  - Cyclopeptide Dmt-[D-Lys-p-CF3-Phe-Phe-Asp]NH2, a novel G protein-biased agonist
      of the mu opioid receptor.
AB  - Opioid peptides and alkaloid drugs such as morphine, mediate their analgesic
      effects, but also undesired side effects, mostly through activation of the mu
      opioid receptor which belongs to the G protein-coupled receptor (GPCR) family. A
      new important pharmacological concept in the field of GPCRs is biased agonism.
      Two mu receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH2 (C-36) and Dmt-c[D-Lys-Phe-p
      CF3-Phe-Asp]NH2 (F-81), were evaluated in terms of their ability to promote or
      block mu receptor/G protein and mu receptor/beta-arrestin interactions. Using the
      bioluminescence resonance energy transfer (BRET) assay it was shown that C-36
      activated both, G protein and beta-arrestin pathways. Incorporation of
      trifluoromethyl group into the aromatic ring of phenylalanine in the sequence of
      F-81 led to activation of G-protein pathway rather than beta-arrestin
      recruitment. Opioid cyclopeptide F-81 turned out to be a biased G protein mu
      receptor agonist. Such biased ligands are able to separate the biological actions
      of an activated receptor and have the potential to become more effective drug
      candidates with fewer side effects.

PMID- 29196182
TI  - Peripheral 5-HT3 mediates mirror-image pain by a cross-talk with acid-sensing ion
      channel 3.
AB  - Mirror-image pain (MIP), which occurs along with complex regional pain syndrome,
      rheumatoid arthritis and chronic migraine, is characterized by increased pain
      sensitivity of healthy body regions other than the actual injured or inflamed
      sites. A high level of peripheral inflammation may activate central or peripheral
      glia, triggering mirror-image pain. However, which receptors mediate inflammatory
      signals to contribute glial activation remains unclear. Intraplantarly injecting
      mice with 5-hydroxytryptamine (5-HT) or acidic buffer (proton) caused only
      unilateral hyperalgesia, but co-injection of 5-HT/acid induced bilateral
      hyperalgesia (MIP). Blocking 5-HT3 or acid-sensing ion channel 3 (ASIC3)
      abolished satellite glial activation, inhibiting MIP. Interestingly, intraplantar
      administration of a 5-HT3 agonist induced MIP, and 5-HT3-mediated MIP can be
      reversed by a 5-HT3 antagonist or an ASIC3 blocker. Similar results were found
      using a ASIC3 agonist. Furthermore, 5-HT3 was observed to co-localize with ASIC3
      in DRG neurons; 5-HT3 activation-induced an increase in intracellular calcium
      that was inhibited by an ASIC3 blocker and vice versa. A cross-talk between 5-HT3
      and ASIC3 mediates satellite glial activation, thereby triggering mirror-image
      pain.

PMID- 29196183
TI  - NMDA receptor antagonist rodent models for cognition in schizophrenia and
      identification of novel drug treatments, an update.
AB  - Negative and cognitive deficit symptoms in schizophrenia remain an unmet clinical
      need. Improved understanding of the neuro- and psychopathology of cognitive
      dysfunction in the illness is urgently required to enhance the development of new
      improved therapeutic strategies. Careful validation of animal models that mimic
      the behaviour and pathology of complex psychiatric disorders is an essential step
      towards this goal. Non-competitive NMDAR (N-Methyl-d-aspartate receptor)
      antagonists e.g. phencyclidine (PCP), ketamine and dizocilpine (MK-801) can
      effectively replicate certain aspects of negative and cognitive deficits
      associated with schizophrenia in animals. In 2010 we reviewed the effects of
      NMDAR antagonism in tests for domains of cognition affected in schizophrenia,
      social behaviour and neuropathology, and in 2014, in tests for negative symptoms.
      In this update, we evaluate the most recent pharmacological strategies for
      restoring cognition in schizophrenia using NMDAR antagonist models, published
      since our original review in 2010 (cited over 225 times, excluding self
      citations). Tests reviewed are, novel object recognition for visual recognition
      memory, attentional set shifting for executive function, and operant tests
      incorporating recent touchscreen technology for a range of domains including
      working memory, problem solving and attention, all impaired in schizophrenia.
      Moreover, we include an update on parvalbumin (PV)-expressing GABAergic
      interneurons and review, for the first time, the effects of NMDAR antagonists on
      gamma oscillations, circuitry integral for effective cognition. Data summarized
      in this review strongly confirm the reliability and usefulness of NMDAR
      antagonist animal models for evaluating novel therapeutic candidates, and for
      improving our understanding of the pathophysiology of cognitive deficits in
      schizophrenia. This article is part of the Special Issue entitled 'Psychedelics:
      New Doors, Altered Perceptions'.

PMID- 29196184
TI  - A Randomized Trial of a Binocular iPad Game Versus Part-Time Patching in Children
      Aged 13 to 16 Years With Amblyopia.
AB  - PURPOSE: To compare visual acuity (VA) improvement in teenagers with amblyopia
      treated with a binocular iPad game vs part-time patching. METHODS: One hundred
      participants aged 13 to <17 years (mean 14.3 years) with amblyopia (20/40 to
      20/200, mean ~20/63) resulting from strabismus, anisometropia, or both were
      enrolled into a randomized clinical trial. Participants were randomly assigned to
      treatment for 16 weeks of either a binocular iPad game prescribed for 1 hour per
      day (n = 40) or patching of the fellow eye prescribed for 2 hours per day (n =
      60). The main outcome measure was change in amblyopic eye VA from baseline to 16
      weeks. RESULTS: Mean amblyopic eye VA improved from baseline by 3.5 letters (2
      sided 95% confidence interval [CI]: 1.3-5.7 letters) in the binocular group and
      by 6.5 letters (2-sided 95% CI: 4.4-8.5 letters) in the patching group. After
      adjusting for baseline VA, the difference between the binocular and patching
      groups was -2.7 letters (95% CI: -5.7 to 0.3 letters, P = .082) or 0.5 lines,
      favoring patching. In the binocular group, treatment adherence data from the iPad
      device indicated that only 13% of participants completed >75% of prescribed
      treatment. CONCLUSIONS: In teenagers aged 13 to <17 years, improvement in
      amblyopic eye VA with the binocular iPad game used in this study was not found to
      be better than patching, and was possibly worse. Nevertheless, it remains unclear
      whether the minimal treatment response to binocular treatment was owing to poor
      treatment adherence or lack of treatment effect.

PMID- 29196186
TI  - Implementation of an expanded point-of-care site inspection checklist in an
      academic medical center: An eight year experience.
AB  - BACKGROUND: We evaluated the effectiveness of an expanded point-of-care (POCT)
      site inspection checklist over an extended 8-y period. METHODS: A retrospective
      review of site inspection deficiency reports in a large academic medical center
      from 2010 to 2017 (year to date). RESULTS: There was a significant decrease in
      the number of cited deficiencies per site/inspection from 2010 (3.17) to 2017
      (0.27) (p<0.001). The percentage of sites without deficiencies steadily increased
      from 2010 (8.7%) to 2017 (80.7%) (p<0.001). The most common citation was
      documentation of competency assessment followed by results documentation and
      annual procedure review. CONCLUSIONS: Regular inspections of sites performing
      POCT are necessary to maintain regulatory compliance. Over time significant
      improvements in compliance are achievable.

PMID- 29196185
TI  - Serum S100A12 and 30-day mortality after acute intracerebral hemorrhage.
AB  - BACKGROUND: S100A12 is implicated in inflammatory reactions. The purpose of this
      study was to determine the association between serum S100A12 concentrations and
      30-day mortality in patients with acute intracerebral hemorrhage (ICH). METHODS:
      We prospectively included 182 healthy controls and 182 ICH patients within 24h
      after stroke onset. Serum samples were collected for the measurement of S100A12
      concentrations. Multivariable analysis was used to evaluate the relationship
      between serum S100A12 concentrations and mortality of ICH patients within 30days.
      RESULTS: Serum S100A12 concentrations were significantly increased compared to
      control subjects. S100A12 concentrations were positively correlated with National
      Institutes of Health Stroke Scale (NIHSS) score, ICH volume, blood glucose
      concentrations, blood white blood cell count and plasma C-reactive protein
      concentrations. 36 (19.8%) patients were deceased within 30days after stroke
      onset. Non-survivors had significantly higher concentrations of serum S100A12
      than survivors. Additionally, Serum S100A12 concentrations significantly
      discriminated patients at risk of 30-day mortality and its predictive value was
      equivalent to those of NIHSS score and hematoma volume. Moreover, higher serum
      S100A12 concentrations showed a significantly higher risk for 30-day mortality
      and overall survival. CONCLUSIONS: Higher S100A12 concentrations are positively
      associated with inflammation, hemorrhagic severity and short-term mortality among
      ICH patients, indicating S100A12 may represent a biomarker for predicting poor
      outcome after hemorrhagic stroke.

PMID- 29196187
TI  - Clinical proteomics: Insights from IGF-I.
AB  - Clinical proteomics aims to deliver cost-effective multiplexing of potentially
      hundreds of diagnostic proteins, including distinct protein isoforms. The
      analytical strategy known as targeted proteomics is particularly promising
      because it is compatible with robust mass spectrometry (MS)-platforms already
      implemented in many clinical laboratories for routine quantitation of small
      molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted
      proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided
      valuable insights about tryptic peptides, transitions, internal standards and
      calibrants. The present challenge is to examine if targeted proteomics of IGF-I
      can truly measure up to the routine performance that must be expected from a
      clinical testing platform.

PMID- 29196188
TI  - Nervous system development and disease: A focus on trithorax related proteins and
      chromatin remodelers.
AB  - The nervous system comprises many different cell types including neurons, glia,
      macrophages, and immune cells, each of which is defined by specific patterns of
      gene expression, morphology, function, and anatomical location. Establishment of
      these complex and highly regulated cell fates requires spatial and temporal
      coordination of gene transcription. Open chromatin (euchromatin) allows
      transcription factors to interact with gene promoters and activate lineage
      specific genes, whereas closed chromatin (heterochromatin) remains inaccessible
      to transcriptional activation. Changes in the genome-wide distribution of
      euchromatin accompany transcriptional plasticity that allows the diversity of
      mature cell fates to be generated during development. In the past 20years, many
      new genes and gene families have been identified to participate in regulation of
      chromatin accessibility. These genes include chromatin remodelers that interact
      with Trithorax group (TrxG) and Polycomb group (PcG) proteins to activate or
      repress transcription, respectively. Here we review the role of TrxG proteins in
      neurodevelopment and disease.

PMID- 29196191
TI  - Arterial spin labeling perfusion MRI signal denoising using robust principal
      component analysis.
AB  - BACKGROUND: Arterial spin labeling (ASL) perfusion MRI provides a non-invasive
      way to quantify regional cerebral blood flow (CBF) and has been increasingly used
      to characterize brain state changes due to disease or functional alterations. Its
      use in dynamic brain activity study, however, is still hampered by the relatively
      low signal-to-noise-ratio (SNR) of ASL data. NEW METHOD: The aim of this study
      was to validate a new temporal denoising strategy for ASL MRI. Robust principal
      component analysis (rPCA) was used to decompose the ASL CBF image series into a
      low-rank component and a sparse component. The former captures the slowly
      fluctuating perfusion patterns while the latter represents spatially incoherent
      spiky variations and was discarded as noise. While there still lacks a way to
      determine the parameter for controlling the balance between the low-rankness and
      sparsity of the decomposition, we designed a method to solve this problem based
      on the unique data structures of ASL MRI. Method evaluations were performed with
      ASL CBF-based functional connectivity (FC) analysis and a sensorimotor functional
      ASL MRI study. COMPARISON WITH EXISTING METHOD(S): The proposed method was
      compared with the component based noise correction method (CompCor). RESULTS: The
      proposed method markedly increased temporal signal-to-noise-ratio (TSNR) and
      sensitivity of ASL CBF images for FC analysis and task activation detection.
      CONCLUSIONS: We proposed a new temporal ASL CBF image denoising method, and
      showed its benefit for the CBF time series-based FC analysis and task activation
      detection.

PMID- 29196190
TI  - p-Benzoquinone-induced aggregation and perturbation of structure and chaperone
      function of alpha-crystallin is a causative factor of cigarette smoke-related
      cataractogenesis.
AB  - Cigarette smoking is a significant risk factor for cataract. However, the
      mechanism by which cigarette smoke (CS) causes cataract remains poorly
      understood. We had earlier shown that in CS-exposed guinea pig, p-benzoquinone (p
      BQ) derived from CS in the lungs is carried by the circulatory system to distant
      organs and induces various smoke-related pathogeneses. Here, we observed that CS
      exposure caused accumulation of the p-BQ-protein adduct in the eye lens of guinea
      pigs. We also observed accumulation of the p-BQ-protein adduct in resected lens
      from human smokers with cataract. No such accumulation was observed in the lens
      of never smokers. p-BQ is a strong arylating agent that forms Michael adducts
      with serum albumin and haemoglobin resulting in alterations of structure and
      function. A major protein in the mammalian eye lens is alphaA-crystallin, which
      is a potent molecular chaperone. alphaA-crystallin plays a key role in
      maintaining the integrity and transparency of the lens. SDS-PAGE indicated that p
      BQ induced aggregation of alphaA-crystallin. Various biophysical techniques
      including UV-vis spectroscopy, fluorescence spectroscopy, FT-IR, bis-ANS
      titration suggested a perturbation of structure and chaperone function of alphaA
      crystallin upon p-BQ modification. Our results indicate that p-BQ is a causative
      agent involved in the modification of alphaA-crystallin and pathogenesis of CS
      induced cataract. Our findings would educate public about the impacts of smoking
      on eye health and help to discourage them from smoking. The study might also help
      scientists to develop new drugs for the intervention of CS-induced cataract at an
      early stage.

PMID- 29196193
TI  - Automated Center-out Rodent Behavioral Trainer (ACRoBaT), an automated device for
      training rats to perform a modified center out task.

PMID- 29196189
TI  - PD-L1, inflammation, non-coding RNAs, and neuroblastoma: Immuno-oncology
      perspective.
AB  - Neuroblastoma is the most common pediatric solid tumor of neural crest origin.
      The current treatment options for neuroblastoma produce severe side effects.
      Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are
      known to play a significant role in the pathogenesis of neuroblastoma. Cancer
      cells and the surrounding cells in the tumor microenvironment express PD-L1.
      Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells.
      The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic
      regulation of the immune system. Chronic inflammation is involved in the
      recruitment of leukocytes, production of cytokines and chemokines that in turn,
      lead to survival, metastasis, and angiogenesis in neuroblastoma tumors. The
      miRNAs and long non-coding (lnc) RNAs have emerged as a novel class of non-coding
      RNAs that can regulate neuroblastoma associated cell-signaling pathways. The
      dysregulation of PD-1/PD-L1, inflammatory pathways, lncRNAs, and miRNAs have been
      reported in clinical and experimental samples of neuroblastoma. These signaling
      molecules are currently being evaluated for their potential as the biomarker and
      therapeutic targets in the management of neuroblastoma. A monoclonal antibody
      called dinutuximab (Unituxin) that attaches to a carbohydrate molecule GD2, on
      the surface of many neuroblastoma cells, is being used as an immunotherapy drug
      for neuroblastoma treatment. Atezolizumab (Tecentriq), an engineered monoclonal
      antibody against PD-L1, are currently in clinical trial for neuroblastoma
      patients. The lncRNA/miRNA-based therapeutics is being developed to deliver tumor
      suppressor lncRNAs/miRNAs or silencing of oncogenic lncRNAs/miRNAs. The focus of
      this review is to discuss the current knowledge on the immune checkpoint
      molecules, PD-1/PD-L1 signaling, inflammation, and non-coding RNAs in
      neuroblastoma.

PMID- 29196192
TI  - Macrovipecetin, a C-type lectin from Macrovipera lebetina venom, inhibits
      proliferation migration and invasion of SK-MEL-28 human melanoma cells and
      enhances their sensitivity to cisplatin.
AB  - BACKGROUND: The resistance of melanoma cells to cisplatin restricts its clinical
      use. Therefore, the search for novel tumor inhibitors and effective combination
      treatments that sensitize tumor cells to this drug are still needed. We purified
      macrovipecetin, a novel heterodimeric C-type lectin, from Macrovipera lebetina
      snake venom and investigated its anti-tumoral effect on its own or combined with
      cisplatin, in human melanoma cells. METHODS: Biochemical characterization, in
      vitro cells assays such as viability, apoptosis, adhesion, migration, invasion,
      Western blotting and in silico analysis were used in this study. RESULTS:
      Macrovipecetin decreased melanoma cell viability 100 times more than cisplatin.
      Interestingly, when combined with the drug, macrovipecetin enhanced the
      sensitivity of SK-MEL-28 cells by augmenting their apoptosis through increased
      expression of the apoptosis inducing factor (AIF) and activation of ERK1/2, p38,
      AKT and NF-kappaB. Moreover, macrovipecetin alone or combined with cisplatin
      induced the expression of TRADD, p53, Bax, Bim and Bad and down-regulated the Bcl
      2 expression and ROS levels in SK-MEL-28 cells. Interestingly, these treatments
      impaired SK-MEL-28 cell adhesion, migration and invasion through modulating the
      function and expression of alphavbeta3 integrin along with regulating E-cadherin,
      vimentin, beta-catenin, c-Src and RhoA expression. In silico study suggested that
      only the alpha chain of macrovipecetin interacts with a region overlapping the
      RGD motif binding site on this integrin. CONCLUSIONS: We validated the antitumor
      effect of macrovipecetin when combined, or not, with cisplatin on SK-MEL-28
      cells. GENERAL SIGNIFICANCE: The presented work proposes the potential use of
      macrovipecetin and cisplatin in combination as an effective anti-melanoma
      treatment.

PMID- 29196194
TI  - Molecular detection and sequence characterization of diverse rhabdoviruses in
      bats, China.
AB  - The Rhabdoviridae is among the most diverse families of RNA viruses and currently
      classified into 18 genera with some rhabdoviruses lethal to humans and other
      animals. Herein, we describe genetic characterization of three novel
      rhabdoviruses from bats in China. Of these, two viruses (Jinghong bat virus and
      Benxi bat virus) found in Rhinolophus bats showed a phylogenetic relationship
      with vesiculoviruses, and sequence analyses indicate that they represent two new
      species within the genus Vesiculovirus. The remaining Yangjiang bat virus found
      in Hipposideros larvatus bats were only distantly related to currently known
      rhabdoviruses.

PMID- 29196195
TI  - Novel expression of immunogenic foot-and-mouth disease virus-like particles in
      Nicotiana benthamiana.
AB  - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed
      animals and is endemic in Africa, parts of South America and southern Asia. The
      causative agent, FMD virus (FMDV) is a member of the genus Aphthovirus, family
      Picornaviridae. Vaccines currently used against FMDV are chemically inactivated
      virus strains which are produced under high-level biocontainment facilities, thus
      raising their cost. The development of recombinant FMDV vaccines has focused
      predominantly on FMDV virus-like particle (VLP) subunit vaccines for which
      promising results have been achieved. These VLPs are attractive candidates
      because they avoid the use of live virus in production facilities, but conserve
      the complete repertoire of conformational epitopes of the virus. Recombinant FMDV
      VLPs are formed by the expression and assembly of the three structural proteins
      VP0, VP1 and VP3. This can be attained by co-expression of the three individual
      structural capsid proteins or by co-expression of the viral capsid precursor P1
      2A together with the viral protease 3C. The latter proteolytically cleaves P1-2A
      into the respective structural proteins. These VLPS are produced in mammalian or
      insect cell culture systems, which are expensive and can be easily contaminated.
      Plants, such as Nicotiana benthamiana, potentially provide a more cost-effective
      and very highly scalable platform for recombinant protein and VLP production. In
      this study, P1-2A was transiently expressed in N. benthamiana alone, without the
      3C protease. Surprisingly, there was efficient processing of the P1-2A
      polyprotein into its component structural proteins, and subsequent assembly into
      VLPs. The yield was ~0.030MUg per gram of fresh leaf material. Partially purified
      VLPs were preliminarily tested for immunogenicity in mice and shown to stimulate
      the production of FMDV-specific antibodies. This study, has important
      implications for simplifying the production and expression of potential vaccine
      candidates against FMDV in plants, in the absence of 3C expression.

PMID- 29196196
TI  - Molluscicidal activity of Manilkara subsericea (Mart.) dubard on Biomphalaria
      glabrata (Say, 1818).
AB  - Schistosomiasis is promoted for species from Schistosoma genus affecting over 200
      million people worldwide. Molluscicides are an efficient method to control this
      disease, being able to reduce intermediate host snail Biomphalaria glabrata
      number. In function of resistance cases using niclosamide, natural products are
      promisors to discover new drugs. Manilkara subsericea is endemic to Brazilian
      sandbanks of Rio de Janeiro State and wide ranges of biological activities.
      However, there is no studies evaluating its effects as molluscicidal agent. We
      tested crude extract from leaves of M. subsericea molluscicidal action, as well
      it ethyl-acetate fraction and isolated substances against B. glabrata. M.
      subsericea leaves crude extract and ethyl acetate fraction induced 80+/-4.13% and
      86.66+/-4.59% mortality of adult snails at concentrations of 250ppm after 96h,
      and their LD50 values were 118.7+/-1.62 and 23.41+/-1.15ppm respectively.
      Isolated substances from M. subsericea were also considered active. Quercetin,
      myricetin and ursolic acid, at concentration of 100ppm (96h), were able to induce
      mortality levels of 100%, 80% and 53.33%, respectively. Our results suggest that
      M. subsericea can be considered promising as a molluscicide agent.

PMID- 29196197
TI  - Behavioral asymmetries in ticks - Lateralized questing of Ixodes ricinus to a
      mechatronic apparatus delivering host-borne cues.
AB  - Ticks are considered among the most dangerous arthropod vectors of disease agents
      to both humans and animals worldwide. Lateralization contributes to biological
      fitness in many animals, conferring important functional advantages, therefore
      studying its role in tick perception would critically improve our knowledge about
      their host-seeking behavior. In this research, we evaluated if Ixodes ricinus
      (L.) (Ixodiidae) ticks have a preference in using the right or the left foreleg
      to climb on a host. We developed a mechatronic device moving a tuft of fox skin
      with fur as host-mimicking combination of cues. This engineered approach allows
      to display a realistic combination of both visual and olfactory host-borne
      stimuli, which is prolonged over the time and standardized for each replicate. In
      the first experiment, the mechatronic apparatus delivered host-borne cues
      frontally, to evaluate the leg preference during questing as response to a
      symmetrical stimulus. In the second experiment, host-borne cues were provided
      laterally, in an equal proportion to the left and to the right of the tick, to
      investigate if the host direction affected the questing behavior. In both
      experiments, the large majority of the tested ticks showed individual-level left
      biased questing acts, if compared to the ticks showing right-biased ones.
      Furthermore, population-level left-biased questing responses were observed post
      exposure to host-mimicking cues provided frontally or laterally to the tick.
      Overall, this is the first report on behavioral asymmetries in ticks of medical
      and veterinary importance. Moreover, the mechatronic apparatus developed in this
      research can be exploited to evaluate the impact of repellents on tick questing
      in highly reproducible standardized conditions.

PMID- 29196198
TI  - Neurosurgical Modeling of Retinal Ischemia-Reperfusion Injury.
AB  - BACKGROUND: A reliable model of ischemia-reperfusion is required to evaluate the
      efficacy and safety of neuroprotective therapies for stroke. We present a novel
      reproducible pterygopalatine-ophthalmic artery ligation model of ischemia
      reperfusion injury in the retina. METHODS: Rats were subjected to ophthalmic
      artery/meningeal sheath ligation (OAML-standard method) or clamping of the
      pterygopalatine-ophthalmic artery (OAC-new method) for 30 minutes. Retinal
      ganglion cell (RGC) survival was assessed by prelabeling with FluoroGold (FG)
      (Santa Cruz Biotechnology, CA, USA) and RNA-binding protein with multiple
      splicing (RBPMS) at 14 days after ischemia, and all results were compared with a
      sham group (n = 7 in each group). RESULTS: RGC density in the normal-uninjured
      (FG-labeled) group was 2111 +/- 38 cells/mm2 (mean +/- standard error of mean)
      and that in the RBPMS-labeled group was 2142 +/- 35 cells/mm2. The OAML procedure
      significantly reduced RGC density to 738 +/- 23 cells/mm2 and 780 +/- 41
      cells/mm2 (P < .001) in the FG-labeled and RBPMS-labeled groups, respectively.
      Similarly, OAC reduced RGC survival to 782 +/- 19 cells/mm2 and 813 +/- 22
      cells/mm2 (P < .001) in the FG-labeled and RBPMS-labeled groups, respectively.
      RGC survival was similar following OAC and OAML models, suggesting that both
      induce comparable levels of damage. However, RGC survival in the OAC model was
      found to have less dispersion than OAML-induced ischemia. CONCLUSIONS: These
      results suggest that the OAC procedure is a reliable reproduction of ischemia
      reperfusion injury that mimics the effects of ophthalmic artery occlusion in
      humans and provides a useful research model for testing manipulations directed
      against pathways involved in RGC ischemic degeneration.

PMID- 29196199
TI  - Midt-Term Results after Fast-Track Prophylactic Carotid Surgery Program: The Risk
      of Overlooking Occult Cancer.
AB  - BACKGROUND: Most guidelines recommend fast-track carotid endarterectomy (CEA)
      within 14 days of the last ischemic event. Long-term survival after fast-track
      CEA is unknown. The purpose of this study was to determine whether the fast-track
      CEA program in our region was associated with a reduced or increased 2-year
      survival and overall complication rate in our population. METHODS: Prospective 2
      year follow-up in patients after the implementation of a fast-track CEA program
      during a period of 31/2 years. Data on recurrent stroke, myocardial infarction,
      and death in a 2-year period after CEA were collected along with the indication
      for surgery and the time from ischemic event to the operation. RESULTS: Two
      hundred patients underwent CEA. The overall complication rate for 30 days was
      3.5% (95% confidence interval [CI], 2%-5%) and 15.5% (95% CI, 13%-18%) for 2
      years. During the 2-year follow-up 17 patients (8.5%; 95% CI, 7%-10%) died. Eight
      patients (4%; 95% CI, 2%-6%) died of advanced cancer (undiagnosed at the index
      event and CEA time). Of the 6 deaths occurring in patients undergoing CEA 14 days
      after the index event or earlier, 5 patients (83%; 95% CI, 55%-95%) died of
      advanced cancer. In the 11 deaths in patients who underwent CEA more than 14 days
      after the index event, 3 patients (27%; 95% CI, 5%-50%) died of cancer. This was
      a statistically significant difference (P = .049). CONCLUSION: Fast-track CEA is
      a safe procedure in selected patients. Our results show a potential significant
      risk of overlooking occult cancer, which may affect the long-term benefit from
      prophylactic CEA.

PMID- 29196200
TI  - Incidental Thrombotic Thrombocytopenic Purpura during Acute Ischemic Stroke and
      Thrombolytic Treatment.
AB  - BACKGROUND: Intravenous tissue plasminogen activator (IV tPA) was shown to be an
      effective treatment for acute ischemic stroke (AIS). According to stroke
      guidelines, there is no need to wait for the complete blood count (CBC) and
      coagulation test results before application of IV alteplase if there is no
      suspected coagulation disorder. In this study, a patient with AIS and thrombotic
      thrombocytopenic purpura (TTP) symptoms during thrombolytic treatment was
      presented. CASE: A 33-year-old male patient was admitted at the 2.5th hour of AIS
      symptoms onset with right hemiparesis and sensorimotor aphasia. Cranial computed
      tomography (CT) and diffusion magnetic resonance imaging did not reveal any
      abnormality. In his medical history, the patient did not have any
      contraindication for thrombolytic treatment. To avoid delays to thrombolytic
      therapy, blood samples were taken, and after that, IV bolus alteplase treatment
      was applied. During maintenance treatment, agitation and vomiting developed. The
      result of blood samples showed less than 26,000 mm3 platelet count and
      maintenance therapy was stopped. In control cranial CT, there was no hemorrhage.
      In the laboratory examination; anemia, low platelet count; increased indirect
      bilirubin, lactate dehydrogenase (LDH) levels were found, and fever was 38.4
      degrees C. Schistocytes were observed in peripheral blood smear and the patient
      was diagnosed as TTP. CONCLUSIONS: Stroke guidelines recommend not to wait for
      the results of CBC and coagulation tests before IV tPA treatment in patients who
      do not have any history of coagulopathy disorder. If possible, before applying IV
      tPA we may wait for the results of coagulation and CBC tests, keeping in mind the
      diseaes with high mortality such as TTP.

PMID- 29196202
TI  - Node-making process in network meta-analysis of nonpharmacological treatment are
      poorly reported.
AB  - OBJECTIVE: To identify methods to support the node-making process in network meta
      analyses (NMAs) of nonpharmacological treatments. STUDY DESIGN AND SETTING: We
      proceeded in two stages. First, we conducted a literature review of guidelines
      and methodological articles about NMAs to identify methods proposed to lump
      interventions into nodes. Second, we conducted a systematic review of NMAs of
      nonpharmacological treatments to extract methods used by authors to support their
      node-making process. MEDLINE and Google Scholar were searched to identify
      articles assessing NMA guidelines or methodology intended for NMA authors.
      MEDLINE, CENTRAL, and EMBASE were searched to identify reports of NMAs including
      at least one nonpharmacological treatment. Both searches involved articles
      available from database inception to March 2016. From the methodological review,
      we identified and extracted methods proposed to lump interventions into nodes.
      From the systematic review, the reporting of the network was assessed as long as
      the method described supported the node-making process. RESULTS: Among the 116
      articles retrieved in the literature review, 12 (10%) discussed the concept of
      lumping or splitting interventions in NMAs. No consensual method was identified
      during the methodological review, and expert consensus was the only method
      proposed to support the node-making process. Among 5187 references for the
      systematic review, we included 110 reports of NMAs published between 2007 and
      2016. The nodes were described in the introduction section of 88 reports (80%),
      which suggested that the node content might have been a priori decided before the
      systematic review. Nine reports (8.1%) described a specific process or
      justification to build nodes for the network. Two methods were identified: (1)
      fit a previously published classification and (2) expert consensus. CONCLUSION:
      Despite the importance of NMA in the delivery of evidence when several
      interventions are available for a single indication, recommendations on the
      reporting of the node-making process in NMAs are lacking, and reporting of the
      node-making process in NMAs seems insufficient.

PMID- 29196201
TI  - Specific Factors to Predict Large-Vessel Occlusion in Acute Stroke Patients.
AB  - BACKGROUND: The effectiveness of thrombectomy for acute ischemic stroke has been
      established, and earlier treatment produces better outcomes. If possible to
      identify large-vessel occlusion (LVO) at the prehospital phase, eligible patients
      can be shipped directly to a hospital that can perform thrombectomy. The purpose
      of this study was to determine factors that are specific to LVO and can be known
      before hospital arrival. METHODS: The subjects were stroke patients during the
      period between July 2014 and June 2016, who had a National Institutes of Health
      Stroke Scale (NIHSS) score of 8 or higher and came to our hospital within 6 hours
      of onset. These patients were divided into an LVO group and a non-LVO group, and
      background factors, mode of onset, individual NIHSS item scores, and blood
      pressure at the time of the visit were retrospectively investigated. The selected
      factors were compared with LVO prediction scales reported in the past. RESULTS:
      There were 196 stroke patients who had NIHSS scores of 8 or higher and arrived at
      the hospital within 6 hours. Of these 196 patients, 56 had LVO. This LVO group
      included a significantly higher number of patients with the 2 items of atrial
      fibrillation (odds ratio [OR], 11.5: 95% confidence interval [CI], 4.04-32.9; P <
      .0001) and systolic blood pressure of 170 mm Hg or lower (OR, 2.99: 95% CI, 1.33
      6.71, P = .008). These 2 items predicted LVO equally to existing LVO prediction
      scales. CONCLUSIONS: The 2 items of atrial fibrillation and systolic blood
      pressure of 170 mm Hg or lower were significantly correlated with LVO.

PMID- 29196203
TI  - Nuclear positioning: A matter of life.

PMID- 29196204
TI  - Underground cryptic speciation within the Maghreb: Multilocus phylogeography
      sheds light on the diversification of the checkerboard worm lizard Trogonophis
      wiegmanni.
AB  - Biogeographic and evolutionary patterns in the North African portion of the
      Western Palaearctic are poorly known. A high fraction of undescribed diversity is
      expected in this region, especially in groups such as reptiles. Here we used
      mitochondrial (12S, 16S, cytb) and nuclear (pomc, rag2, cmos) markers and
      morphological data to investigate phyletic diversification and phylogeographical
      structure in the amphisbaenian Trogonophis wiegmanni endemic to the Maghreb.
      Phylogenetic and molecular dating analyses based on gene trees and species trees
      support three deeply divergent lineages of Pliocene origin, two in Morocco and
      one in central Algeria and Tunisia. Parapatry, reciprocal monophyly, high genetic
      divergence and limited morphological differentiation between them suggest that
      these lineages represent independent cryptic taxonomic units. Emerging lines of
      evidence from this study and from available literature on Maghreb taxa support
      (i) a major biogeographic break between western and eastern Maghreb and (ii) a
      role of the Atlas as a biogeographic divide within the western Maghreb (Morocco).
      The origin of these biogeographic units is probably associated with the
      evolutionary events prompted by the Late Miocene palaeogeographic setting and
      later by Plio-Pleistocene climatic changes and their interplay with prominent
      orographic barriers within North Africa.

PMID- 29196205
TI  - Alternative methods of phylogenetic inference for the Patagonian lizard group
      Liolaemus elongatus-kriegi (Iguania: Liolaemini) based on mitochondrial and
      nuclear markers.
AB  - We present different approaches to a multi-locus phylogeny for the Liolaemus
      elongatus-kriegi group, including almost all species and recognized lineages. We
      sequenced two mitochondrial and five nuclear gene regions for 123 individuals
      from 35 taxa, and compared relationships resolved from concatenated and species
      tree methods. The L. elongatus-kriegi group was inferred as monophyletic in three
      of the five analyses (concatenated mitochondrial, concatenated mitochondrial +
      nuclear gene trees, and SVD quartet species tree). The mitochondrial gene tree
      resolved four haploclades, three corresponding to the previously recognized
      complexes: L. elongatus, L. kriegi and L. petrophilus complexes, and the L.
      punmahuida group. The BEAST species tree approach included the L. punmahuida
      group within the L. kriegi complex, but the SVD quartet method placed it as
      sister to the L. elongatus-kriegi group. BEAST inferred species of the L.
      elongatus and L. petrophilus complexes as one clade, while SVDquartet inferred
      these two complexes as monophyletic (although with no statistical support for the
      L. petrophilus complex). The species tree approach also included the L.
      punmahuida group as part of the L. elongatus-kriegi group. Our study provides
      detailed multilocus phylogenetic hypotheses for the L. elongatus-kriegi group,
      and we discuss possible reasons for differences in the concatenation and species
      tree methods.

PMID- 29196206
TI  - Divergence of protein sensing (TLR 4, 5) and nucleic acid sensing (TLR 3, 7)
      within the reptilian lineage.

PMID- 29196207
TI  - Inflammation and fibrosis.
AB  - Tissue damage and inflammation are important triggers for regeneration and
      fibrosis. Tissue damage not only induces inflammation in general, it also
      determines the type and polarization of inflammation by recruiting and activating
      a variety of different cells types of the innate and adaptive immune system. This
      review focuses on the pathways leading from tissue damage to inflammation, from
      inflammation to fibrosis and from fibrosis to function. It covers the pro- and
      antifibrotic properties of immunological mediators released from T cells,
      monocytes/macrophages, innate lymphoid cells, basophils and eosinophils and takes
      into account that extracellular matrix proteins are not only produced by
      mesenchymal fibroblasts but also by other cell types, especially infiltrating
      hematopoietic cells. The special requirements for activation and recruitment of
      these so called fibrocytes are described in detail.

PMID- 29196208
TI  - eRADicAte: A Prospective Evaluation Combining Radium-223 Dichloride and
      Abiraterone Acetate Plus Prednisone in Patients With Castration-Resistant
      Prostate Cancer.
AB  - BACKGROUND: Multiple castration-resistant prostate cancer (CRPC) therapies are
      approved by the United States Food and Drug Administration. Radium-223 dichloride
      (Ra-223) with abiraterone acetate plus prednisone have different mechanisms of
      action and distinct off-target side-effect profiles. We prospectively
      investigated their combined safety, tolerability, and patient-reported outcome
      measures. PATIENTS AND METHODS: eRADicAte, an investigator-initiated, phase II
      trial, studied 31 patients with metastatic CRPC, from 5 United States uro
      oncology research sites. Patients completed 6 cycles of Ra-223 with concurrent
      abiraterone therapy. Quality of life and pain were assessed using the Functional
      Assessment of Cancer Therapy-Prostate and the Brief Pain Inventory-Short Form
      questionnaires and their subscales; we reported the number of subjects meeting
      standardized criteria for clinically meaningful improvements on each scale.
      Safety assessment included Eastern Cooperative Oncology Group performance status,
      laboratory changes, opioid use, radiographic responses, and adverse events (AEs).
      RESULTS: Twenty of 31 (65%) experienced positive clinically meaningful
      improvement changes on the Functional Assessment of Cancer Therapy-Prostate, and
      25 (81%) of 31 on the Prostate Cancer Subscale. Eighteen (58%) of 31 demonstrated
      reduced pain intensity and 12 (39%) of 31 demonstrated reduction of pain
      interference in their lives. At baseline, subjects averaged 11.6 +/- 2.8 bone
      lesions; at the end of treatment, subjects averaged 5.6 +/- 2.4 bone lesions (P =
      .0002). The most frequent AEs were diarrhea (17%), nausea (17%), and fatigue
      (14%). There were 6 serious AEs; 1 led to study withdrawal. CONCLUSIONS: Patients
      experienced clinically meaningful improvements in quality of life and pain,
      without unexpected adverse toxicities. Phase III combination trials of Ra-223
      with novel oral hormonal agents are ongoing to further evaluate radiographic
      progression and overall survival benefit.

PMID- 29196209
TI  - Pathologic Outcomes of Gleason 6 Favorable Intermediate-Risk Prostate Cancer
      Treated With Radical Prostatectomy: Implications for Active Surveillance.
AB  - BACKGROUND: The safety of active surveillance (AS) for Gleason 6 favorable
      intermediate-risk (FIR) prostate cancer is unknown. To provide guidance, we
      examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR
      patients treated with radical prostatectomy. PATIENTS AND METHODS: We identified
      2807 men in the National Cancer Database diagnosed from 2010 to 2012 with Gleason
      6 FIR disease (<50% positive biopsy cores [PBC] with either prostate-specific
      antigen [PSA] of 10-20 ng/mL or cT2b-T2c disease) treated with radical
      prostatectomy. Logistic regression was used to identify predictors of upgrading
      (Gleason 3+4 with tertiary Gleason 5 or Gleason >=4+3) or upstaging (pT3-4/N1).
      RESULTS: Fifty-seven percent of the cohort had PSA of 10 to 20 ng/mL; 25.5%
      patients with PSA of 10 to 20 ng/mL and 12.4% with cT2b to T2c disease were
      upgraded or upstaged. In multivariable analysis, predictors of upgrading or
      upstaging included increasing age (P = .026), PSA (P = .001), and percent PBC (P
      < .001), and black race versus white (P = .035) for patients with PSA of 10 to 20
      ng/mL and increasing PSA (P = .001) and percent PBC (P < .001) for patients with
      cT2b to T2c disease. Men with PSA of 15.0 to 20.0 ng/mL or 37.5% to 49.9% PBC
      with PSA of 10 to 20 ng/mL had >30% risk of upgrading or upstaging, whereas cT2b
      to T2c patients with <12.5% PBC or PSA <5.0 ng/mL had <10% risk. CONCLUSION: We
      found that Gleason 6 FIR patients with cT2b to T2c tumors had a low risk of
      harboring higher grade or stage disease and would be reasonable AS candidates,
      whereas patients with PSA of 10 to 20 ng/mL had a high risk and might generally
      be poor AS candidates.

PMID- 29196211
TI  - Corrigendum to "Timing of autophagy and apoptosis during posterior silk gland
      degeneration in Bombyx mori" [Arthropod Struct. Dev. 46 (4) (2017) 518-528].

PMID- 29196210
TI  - Quantification of M13 and T7 bacteriophages by TaqMan and SYBR green qPCR.
AB  - TaqMan and SYBR Green quantitative PCR (qPCR) methods were developed as DNA-based
      approaches to reproducibly enumerate M13 and T7 phages from phage display
      selection experiments individually and simultaneously. The genome copies of M13
      and T7 phages were quantified by TaqMan or SYBR Green qPCR referenced against M13
      and T7 DNA standard curves of known concentrations. TaqMan qPCR was capable of
      quantifying M13 and T7 phage DNA simultaneously with a detection range of
      2.75*101-2.75*108genome copies(gc)/MUL and 2.66*101-2.66*108 genome
      copies(gc)/MUL respectively. TaqMan qPCR demonstrated an efficient amplification
      efficiency (Es) of 0.97 and 0.90 for M13 and T7 phage DNA, respectively. SYBR
      Green qPCR was ten-fold more sensitive than TaqMan qPCR, able to quantify 2.75
      2.75*107gc/MUL and 2.66*101-2.66*107gc/MUL of M13 and T7 phage DNA, with an
      amplification efficiency Es of 1.06 and 0.78, respectively. Due to its superior
      sensitivity, SYBR Green qPCR was used to enumerate M13 and T7 phage display
      clones selected against a cell line, and quantified titers demonstrated accuracy
      comparable to titers from traditional double-layer plaque assay. Compared to
      enzyme linked immunosorbent assay, both qPCR methods exhibited increased
      detection sensitivity and reproducibility. These qPCR methods are reproducible,
      sensitive, and time-saving to determine their titers and to quantify a large
      number of phage samples individually or simultaneously, thus avoiding the need
      for time-intensive double-layer plaque assay. These findings highlight the
      attractiveness of qPCR for phage enumeration for applications ranging from
      selection to next-generation sequencing (NGS).

PMID- 29196212
TI  - Axl activation attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-kappaB
      pathway after MCAO in rats.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke activates Toll-like receptors (TLRs),
      triggering rapid inflammatory cytokine production. Axl signaling has multiple
      roles, including regulating cytokine secretion, clearing apoptotic cells, and
      maintaining cell survival, however, its role in inflammation after ischemic
      stroke has not been examined. We hypothesized that activation of Axl by
      recombinant Growth-arrest-specific protein 6 (rGas6) attenuates neuroinflammation
      by inhibiting the TLR/TRAF/NF-kappaB pathway after middle cerebral artery
      occlusion (MCAO) in rats. METH: Sprague-Dawley rats were subjected to 2h of MCAO.
      One hour after reperfusion, the rats were given an intranasal injection of rGas6,
      vehicle, or R428 (Axl receptor inhibitor). Neurological scores, infarct volumes,
      immunofluorescence staining, Morris Water Maze, rotarod test and histology
      alterations were analyzed. The expressions of proinflammatory cytokines,
      including IL-1beta, IL-6, TNF-alpha, and Gas6, Axl, STAT1, SOCS1, SOCS3 and the
      TLR/TRAF/NF-kappaB pathway were quantified using Western blot. RESULTS:
      Endogenous expressions of Gas6 and Axl decreased significantly by 24h after MCAO.
      rGas6 reduced brain infarction and improved neurologic deficits scores, and
      increased expression of Axl and decreased the expressions of TRAF3, TRAF6 and
      inflammatory factors IL-1beta, IL-6, and TNF-alpha. Four weeks after MCAO, rGas6
      improved long-term neurological behavior and memory. Inhibition of the
      Axl/TLR/TRAF/NF-kappaB pathway reversed the brain protection by rGas6.
      CONCLUSION: rGas6 reduced the neurological deficits by inhibiting
      neuroinflammation via the TLR/TRAF/NF-kappaB signaling pathway. rGas6 can be used
      as potential treatment to ischemic stroke.

PMID- 29196213
TI  - Ifngr1 and Stat1 mediated canonical Ifn-gamma signaling drives nigrostriatal
      degeneration.
AB  - Brain expression of AAV-Ifn-gamma leads to reactive gliosis, nigrostriatal
      degeneration and midbrain calcification in wild type mice. This mouse model
      phenocopies idiopathic basal ganglia calcification which is associated with
      Parkinsonian symptoms. To understand how the nigro-striatal pathway is
      selectively vulnerable to Ifn-gamma, we determined if the phenotype is driven by
      canonical signaling intermediates, Ifngr1 and Stat1. Using focused bioinformatic
      analysis and rotarod testing, we show that neuroinflammation and motor
      abnormalities precede the appearance of midbrain neuropathologies in the brains
      of Ifn-gamma mouse model. To test whether canonical Ifn-gamma signaling is a key
      driver of progressive nigrostriatal degeneration, we overexpressed Ifn-gamma in
      the brains of Ifngr1-/- and Stat1-/- mice. Expression of Ifn-gamma in Ifngr1-/-
      mice did not result in any neuroinflammation, midbrain calcinosis or
      nigrostriatal degenerative pathology. Interestingly, in Stat1-/- mice, Ifn-gamma
      expression resulted in gliosis without recapitulating the neurodegenerative
      phenotype. Overall, our data shows that canonical Ifn-gamma signaling triggers
      midbrain calcinosis and nigrostriatal neurodegeneration, providing mechanistic
      insights into cytokine-driven selective neuronal vulnerability. Our study
      establishes the broader relevance of inflammatory signaling in neurodegenerative
      diseases and can potentially identify novel immunological targets for
      Parkinsonian syndromes.

PMID- 29196215
TI  - Critical role for Annexin A7 in secondary brain injury mediated by its
      phosphorylation after experimental intracerebral hemorrhage in rats.
AB  - Glutamate excitotoxicity has been implicated in intracerebral hemorrhage (ICH)
      induced secondary brain injury (SBI). Synaptosome associated protein 23 (SNAP23)
      and SNAP25 are respectively participate in presynaptic glutamate release and
      postsynaptic glutamate receptor (NMDA receptor) trafficking, both of which are
      essential for glutamate-mediated excitatory toxicity. SNAP23 and SNAP25 exhibit
      high homology and SNAP23 has been shown to interact with Annexin A7 (ANXA7). This
      study was to examine the role of ANXA7 in ICH-induced neuronal damage. A
      collagenase ICH model was performed in adult male Sprague Dawley rats. First, a
      possible relationship between ANXA7 and ICH pathology was confirmed by an
      increase in the protein and mRNA level of ANXA7 in the brain tissue around
      hematoma of ICH rats and the rescue effects of ANXA7 knockdown in vivo on
      neuronal death, blood-brain barrier damage, brain edema, neurobehavioral
      deficient, and inflammatory response. In addition, the rescue effect of ANXA7
      knockdown on neurobehavioral deficient was also verified in rat autologous blood
      injection ICH model. Second, we found that ICH significantly increased the
      phosphorylation ratio of ANXA7 at the threonine residues mainly in neurons.
      Finally, based on site-specific mutagenesis, we identified that ANXA7
      phosphorylation at threonine 286 is required for its interaction with SNAP25 at
      presynaptic axon terminal and SNAP23 at postsynaptic axon terminal. Collectively,
      our findings suggest that ANXA7 contributed to SBI at least partially through
      regulating glutamate toxicity after ICH. Selective inhibition of ANXA7
      phosphorylation may be a novel approach to ameliorate ICH-induced SBI.

PMID- 29196214
TI  - The lysosomal enzyme alpha-Galactosidase A is deficient in Parkinson's disease
      brain in association with the pathologic accumulation of alpha-synuclein.
AB  - The aberrant accumulation of alpha-synuclein (alpha-syn) is believed to
      contribute to the onset and pathogenesis of Parkinson's disease (PD). The
      autophagy-lysosome pathway (ALP) is responsible for the high capacity clearance
      of alpha-syn. ALP dysfunction is documented in PD and pre-clinical evidence
      suggests that inhibiting the ALP promotes the pathological accumulation of alpha
      syn. We previously identified the pathological accumulation of alpha-syn in the
      brains of mice deficient for the soluble lysosomal enzyme alpha-Galactosidase A
      (alpha-Gal A), a member of the glycosphingolipid metabolism pathway. In the
      present study, we quantified alpha-Gal A activity and levels of its
      glycosphingolipid metabolites in postmortem temporal cortex specimens from
      control individuals and in PD individuals staged with respect to alpha-syn
      containing Lewy body pathology. In late-state PD temporal cortex we observed
      significant decreases in alpha-Gal A activity and the 46kDa "active" species of
      alpha-Gal A as determined respectively by fluorometric activity assay and western
      blot analysis. These decreases in alpha-Gal A activity/levels correlated
      significantly with increased alpha-syn phosphorylated at serine 129 (p129S-alpha
      syn) that was maximal in late-stage PD temporal cortex. Mass spectrometric
      analysis of 29 different isoforms of globotriaosylceramide (Gb3), a substrate of
      alpha-Gal A indicated no significant differences with respect to different stages
      of PD temporal cortex. However, significant correlations were observed between
      increased levels of several Gb3 isoforms and with decreased alpha-Gal A activity
      and/or increased p129S-alpha-syn. Deacylated Gb3 (globotriaosylsphingosine or
      lyso-Gb3) was also analyzed in PD brain tissue but was below the limit of
      detection of 20pmol/g. Analysis of other lysosomal enzymes revealed a significant
      decrease in activity for the lysosomal aspartic acid protease cathepsin D but not
      for glucocerebrosidase (GCase) or cathepsin B in late-stage PD temporal cortex.
      However, a significant correlation was observed between decreasing GCase activity
      and increasing p129S-alpha-syn. Together our findings indicate alpha-Gal A
      deficiency in late-stage PD brain that correlates significantly with the
      pathological accumulation of alpha-syn, and further suggest the potential for
      alpha-Gal A and its glycosphingolipid substrates as putative biomarkers for PD.

PMID- 29196217
TI  - Huntington's disease leads to decrease of GABA-A tonic subunits in the D2
      neostriatal pathway and their relocalization into the synaptic cleft.
AB  - GABA is a widely distributed inhibitory neurotransmitter. GABA-A receptors are
      hetero-pentameric channels assembled in multiple combinations from 19 available
      subunits; this diversity mediates phasic and tonic inhibitory synaptic
      potentials. Whereas GABA-A phasic receptors are located within the synaptic
      cleft, GABA-A tonic receptors are found peri- or extra-synaptically, where they
      are activated by diffusion of synaptic GABA release. In the neostriatum, GABA-A
      tonic subunits are present in the D2 medium-size spiny neurons. Since early
      impairment of these neurons is observed in Huntington's disease, we determined
      the ultrastructural localization of GABA-A-alpha5, -beta3, -delta, -rho2 and, for
      the first time, of GABA-A-rho3 subunits, in the D2 pathway of the YAC128 murine
      model of Huntington's disease at various stages of disease progression. We report
      mislocalization of all five subunits from peri- and extra-synaptic spaces into
      the synaptic clefts of YAC128 mice, present in diseased mice as early as 6 months
      old. The synaptic localization of GABA-A tonic receptors correlated with
      increased sensitivity to pharmacologic antagonists during extracellular
      electrophysiological recordings in neostriatal slices. Finally, the association
      of GABA-A tonic receptors with the D2 pathway in 6-month-old mice was largely
      lost at 12 months of age.

PMID- 29196216
TI  - A third copy of the Down syndrome cell adhesion molecule (Dscam) causes synaptic
      and locomotor dysfunction in Drosophila.
AB  - Down syndrome (DS) is caused by triplication of chromosome 21 (HSA21). It is
      characterised by intellectual disability and impaired motor coordination that
      arise from changes in brain volume, structure and function. However, the
      contribution of each HSA21 gene to these various phenotypes and to the causal
      alterations in neuronal and synaptic structure and function are largely unknown.
      Here we have investigated the effect of overexpression of the HSA21 gene DSCAM
      (Down syndrome cell adhesion molecule), on glutamatergic synaptic transmission
      and motor coordination, using Drosophila expressing three copies of Dscam1.
      Electrophysiological recordings of miniature and evoked excitatory junction
      potentials at the glutamatergic neuromuscular junction of Drosophila larvae
      showed that the extra copy of Dscam1 changed the properties of spontaneous and
      electrically-evoked transmitter release and strengthened short-term synaptic
      depression during high-frequency firing of the motor nerve. Behavioural analyses
      uncovered impaired locomotor coordination despite preserved gross motor function.
      This work identifies DSCAM as a candidate causative gene in DS that is sufficient
      to modify synaptic transmission and synaptic plasticity and cause a DS
      behavioural phenotype.

PMID- 29196219
TI  - Diet-induced insulin resistance state disturbs brain clock processes and alters
      tuning of clock outputs in the Sand rat, Psammomys obesus.
AB  - Reciprocal interactions closely connect energy metabolism with circadian
      rhythmicity. Altered clockwork and circadian desynchronization are often linked
      with impaired energy regulation. Conversely, metabolic disturbances have been
      associated with altered autonomic and hormonal rhythms. The effects of high
      energy (HE) diet on the master clock in the suprachiasmatic nuclei (SCN) remain
      unclear.This question was addressed in the Sand rat (Psammomys obesus), a non
      insulin-dependent diabetes mellitus (NIDDM) animal model. The aim of this work
      was to determine whether enriched diet in Psammomys affects locomotor activity
      rhythm, as well as daily oscillations in the master clock of the SCN and in an
      extra-SCN brain oscillator, the piriform cortex. Sand rats were fed during 3
      months with either low or HE diet. Vasoactive intestinal peptide (VIP),
      vasopressin (AVP) and CLOCK protein cycling were studied by immunohistochemistry
      and running wheel protocol was used for behavioral analysis. High energy feeding
      dietary triggered hyperinsulinemia, impaired insulin/glucose ratio and disruption
      in pancreatic hormonal rhythms. Circadian disturbances in hyper-insulinemic
      animals include a lengthened rest/activity rhythm in constant darkness, as well
      as disappearance of daily rhythmicity of VIP, AVP and the circadian transcription
      factor CLOCK within the suprachiasmatic clock. In addition, daily rhythmicity of
      VIP and CLOCK was abolished by HE diet in a secondary brain oscillator, the
      piriform cortex. Our findings highlight a major impact of diabetogenic diet on
      central and peripheral rhythmicity. The Psammomys model will be instrumental to
      better understand the functional links between circadian clocks, glucose
      intolerance and insulin resistance state.

PMID- 29196220
TI  - New chalcone compound as a promising antileishmanial drug for an old neglected
      disease: Biological evaluation using radiolabelled biodistribution.
AB  - OBJECTIVES: Treatment of leishmaniasis remains a challenge, especially due to the
      need for multiple painful injections, the toxicity of current drugs against the
      disease, their lack of efficacy and, lately, drug resistance. The aim of this
      study was to demonstrate the biological behaviour of 3-nitro-2'-hydroxy-4',6'
      dimethoxychalcone (CH8) in a murine model of cutaneous leishmaniasis (CL) and
      visceral leishmaniasis (VL). METHODS: To evaluate its biological behaviour,
      compound CH8 was radiolabelled with technetium-99m (99mTc) using the direct
      reaction. Groups of animals infected with ether Leishmania infantum (as a model
      for VL) or Leishmania amazonensis (as a model for CL) were administered CH8-99mTc
      orally or subcutaneously, respectively, and its biodistribution was evaluated.
      RESULTS: Oral administration of CH8-99mTc resulted in poor absorption. However,
      the absorbed drug was expressively taken up in the blood and liver, the main
      organ infected in VL. CH8-99mTc administered by the subcutaneous route showed a
      poor distribution and significant uptake in the left ear, suggesting a local
      effect in the skin. In addition, the VL and CL infection models did not
      considerably alter the biodistribution profile by the oral and subcutaneous
      routes, respectively. CONCLUSION: These results suggest that CH8 is a promising
      candidate for oral treatment of VL and for intralesional treatment of CL, showing
      a prominent local effect.

PMID- 29196218
TI  - Stress-induced hippocampus Npas4 mRNA expression relates to specific
      psychophysiological patterns of stress response.
AB  - Neuronal Per-Arnt-Sim (PAS) domain protein 4 (Npas4) is a key protein that
      intervenes in GABA synapse scaling and neurotrophicity enhancing. Since GABA and
      neurotrophicity are implicated in stress response and Npas4-deficient rodents
      exhibit behavioral alterations, an investigation was designed in rats to verify
      whether stress-induced spontaneous hippocampus Npas4 mRNA expression would be
      associated with specific patterns of stress response. The rats were exposed to
      one of three stressor levels: no stress (CTL, n = 15), exposure to a footshock
      apparatus (Sham, S, n = 40) and footshock (F, n = 80). After stress exposure the
      S and F rats were tested in an activity cage, and subsequently in an elevated
      plus maze (EPM), just prior to the sacrifice. Using cluster analysis, the animals
      already assigned to a stress level were also distributed into 2 subgroups
      depending on their Npas4 mRNA levels. The low (L) and high (H) Npas4 expression
      subgroups were identified in the S and F groups, the CTL group being independent
      of the Npas4 levels. The Npas4 effect was studied through the interaction between
      stress (S and F) and Npas4 level (L and H). The biological stress response was
      similar in H and L rats, except blood corticosterone that was slightly lower in
      the H rats. The H rats were more active in the actimetry cage and presented
      higher levels of exploration in the EPM. They also exhibited higher hippocampus
      activation, as assessed by the c-fos, Egr1 and Arc mRNA levels. Therefore high
      Npas4 expression favors stress management.

PMID- 29196221
TI  - Characterisation of methicillin-resistant Staphylococcus aureus with reduced
      susceptibility to ceftaroline collected in Russia during 2010-2014.

PMID- 29196223
TI  - Mild hyperbaric oxygen inhibits the decrease of dopaminergic neurons in the
      substantia nigra of mice with MPTP-induced Parkinson's disease.
AB  - We examined whether exposure to mild hyperbaric oxygen inhibits the decrease of
      dopaminergic neurons in the substantia nigra of a neurotoxic animal model with
      Parkinson's disease. Mice injected with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine hydrochloride and probenecid twice a week were divided into
      two groups: mice with mild hyperbaric oxygen and those without. The mice with
      mild hyperbaric oxygen were exposed to 1317hPa with 45% oxygen for 3h, three
      times a week. The decrease in dopaminergic neurons of mice with Parkinson's
      disease was inhibited by 11 weeks of exposure to mild hyperbaric oxygen. We
      conclude that exposure to mild hyperbaric oxygen is effective in preventing the
      progression of Parkinson's disease.

PMID- 29196222
TI  - Volvulus of the sigmoid colon is associated with hypotrophy of the left lateral
      segment of the liver and the absence of sigmoid diverticulum.
AB  - PURPOSE: To investigate the possible relationships between sigmoid diverticula,
      the volume of the left lateral segment of the liver and sigmoid colon volvulus.
      MATERIAL AND METHODS: The presence of sigmoid diverticula was analyzed in 36
      patients (24 men, 12 women; mean age, 70.77+/-19.86 [SD] years) with sigmoid
      volvulus (group 1). The volumes of left lateral segment of the liver (i.e.,
      segments 2 and 3 and further referred to as liver 1), liver 2 (i.e., segments 1,
      4, 5, 6, 7 and 8), total liver volume and liver volume ratio (LVR) (i.e., [liver
      1/liver 2]*100) were calculated from abdominal CT performed distantly from the
      acute episode of sigmoid volvulus. Results of volumetric measurements in group 1
      were compared with those of two groups of age and gender-matched control patients
      without hepatopathy: one patient group with sigmoid diverticula (group 2) and one
      group without sigmoid diverticula (group 3). RESULTS: No patients with sigmoid
      volvulus had diverticulum. Liver 1 volume was lower in group 1 (193.8cm3) than in
      group 2 (273.75cm3) (P=0.0003). Mean LVR was greater in group 2 (24.18%) than in
      group 1 (14.46%) (P=1*10-7) and group 3 (18.36%) (P=0.003). Mean LVR was greater
      in group 3 than in group 1 (P=0.01). No significant differences in liver 2 volume
      and total liver volumes were found between the 3 groups. CONCLUSION: Elasticity
      of colon wall associated with relative hypotrophy of left lateral segment of the
      liver are significantly associated with sigmoid volvulus. Further studies are
      needed to elucidate the pathophysiological mechanisms behind this association.

PMID- 29196224
TI  - Phosphorylation of Mig6 negatively regulates the ubiquitination and degradation
      of EGFR mutants in lung adenocarcinoma cell lines.
AB  - Activating mutations in the kinase domain of epidermal growth factor receptor
      (EGFR) leads to the constitutively active kinase, improves the EGFR stability and
      promotes malignant transformation in lung adenocarcinoma. Despite the clinical
      significance, the mechanism by which the increased kinase activity stabilizes the
      receptor is not completely understood. Using SILAC phosphoproteomic approach, we
      identify that Mig6 is highly phosphorylated at S256 in EGFR mutants (19del and
      L858R). Loss of Mig6 contributes to the efficient degradation of EGFR wildtype
      and mutants in lung cancer cells. Mig6 regulates the recruitment of c-Cbl to EGFR
      as the ablation of Mig6 enables efficient ubiquitination of the EGFR mutants
      through elevated recruitment of c-Cbl. We show that the cells with activating
      mutants of EGFR inactivate Mig6 through phosphorylation at S256. Inactivated Mig6
      causes inefficient ubiquitination of EGFR, leading to defective degradation of
      the receptor thus contributing to the increased stability of the receptor. Taken
      together, we show a novel function of Mig6 in regulating the ubiquitination of
      EGFR.

PMID- 29196225
TI  - Hip prostheses in young adults. Surface prostheses and short-stem prostheses.
AB  - The poor results obtained in young patients when using a conventional prosthesis
      led to the resurgence of hip resurfacing to find less invasive implants for the
      bone. Young patients present a demand for additional activity, which makes them a
      serious challenge for the survival of implants. In addition, new information
      technologies contribute decisively to the preference for non-cemented prostheses.
      Maintaining quality of life, preserving the bone and soft tissues, as well as
      achieving a very stable implant, are the goals of every hip orthopaedic surgeon
      for these patients. The results in research point to the use of smaller
      prostheses, which use the metaphyseal zone more and less the diaphyseal zone, and
      hence the large number of the abovementioned short stem prostheses. Both models
      are principally indicated in the young adult. Their revision should be a more
      simple operation, but this is only true for hip resurfacing, not for short stems.

PMID- 29196226
TI  - Clinical assessment of patients with isolated hip fractures associated with an
      upper limb fracture.
AB  - INTRODUCTION: Some patients with a hip fracture also present a concomitant upper
      limb fracture. We want to know whether these patients have a worse functional
      level and whether they have any differences in various clinical parameters
      compared with patients with an isolated hip fracture. MATERIAL AND METHODS: We
      retrospectively reviewed 1061 discharge reports from the Orthogeriatrics Unit. We
      collected information on several clinical parameters of the fractures.
      Subsequently, we performed a statistical analysis of the data by comparing the
      associated fracture group with the isolated fracture group. RESULTS: We detected
      44 patients with associated upper limb fracture, 90.9% were women (40) and the
      average age was 84.45years. Eighty-one point eight percent of the upper limb
      fractures were distal radius or proximal humerus. Pertrochanteric fractures were
      the most common (none of them were subtrochanteric fractures). Surgical delay was
      2.60days and the average hospital stay was 12.30days. Sixty-four point three
      percent were nail surgery and 31% arthroplasty. The mean Barthel index score was
      84.88 (P=.021). Fifty-two point 5 percent of the patients in the study group were
      referred to a functional support unit (P=.03). The in-hospital mortality rate was
      4.2%, with no differences between groups. CONCLUSIONS: Patients with an
      associated fracture have a higher previous functional capacity and they are more
      independent. Nevertheless, after the fracture they need more help from the
      healthcare system for optimal functional recovery.

PMID- 29196227
TI  - Scaphoid Fractures treated with a volar percutaneous approach. Analysis and
      results in 92 cases.
AB  - OBJECTIVE: Herbert type B1 and B2 scaphoid fractures can be treated by
      orthopaedic treatment or surgery. The aim of this study is to analyse results and
      complications of scaphoid waist fractures treated using the percutaneous volar
      approach. MATERIAL AND METHOD: We present a retrospective study of 92 patients,
      treated in our institution from 2006 to 2016 using a volar percutaneous fixation.
      Mean Follow-up was 16 months (range 12-48). Injuries were classified using
      Hebert's classification, including B1 and B2 fracture types; the other fracture
      types following this classification system were excluded. Politrauma patients,
      dorsal approach, fractures associated with distal radius injuries, patients
      treated using another surgical technique and patients with non follow-up were
      also excluded. Functional results were evaluated using the DASH questionnaire.
      Consolidation was established as the presence of bony bridges crossing the
      fracture site on x-rays, associated with absence of pain. RESULTS: The average
      time to fracture healing was 6.6 weeks (range 5-11). After 12 months of follow
      up, the average wrist range of motion was 70 degrees  of extension (range 58-75)
      and 70 degrees  of flexion (range 62-80). Regarding functional evaluation, the
      average DASH questionnaire score was 42. The most frequent complication was non
      union in 4 cases (4.44%). Average surgical time was 25min. CONCLUSIONS: Volar
      percutaneous fixation is a simple and quick technique for a specialist surgeon,
      characterised by low morbidity and complication rates compared to ORIF and
      orthopaedic treatment, which accelerates the patient's functional recovery.

PMID- 29196228
TI  - Factors related to skeletal relapse in the two-jaw surgery treatment of
      mandibular prognathism.
AB  - This study identified factors contributing to skeletal relapse in the two-jaw
      surgery treatment of mandibular prognathism. A set of three standardized lateral
      cephalograms (T1: before surgery, T2: immediately after surgery, T3: final follow
      up after surgery) were obtained from 35 patients. The surgical changes were
      defined as follows: postsurgical immediate change (T2-T1), postoperative
      stability (T3-T2) and the final surgical change (T3-T1). The occlusal plane and
      gonial angles were also measured. Relapse was defined as the reverse movements of
      the menton point (Me) and point A, with the null hypothesis stating that Me and
      point A do not significantly change at the postoperative stability (T3-T2). A
      paired t test and Pearson's correlation were used for statistical analysis. The
      immediate postoperative changes (T2-T1) in Me and point A were significant, and
      were measured to be 8.5mm backward and 3.0mm forward, respectively. Additionally,
      the occlusal plane and gonial angles significantly increased by 2 degrees  and
      decreased by 2 degrees , respectively. The final postoperative changes (T3-T1) in
      Me and point A were also significant, and were measured to be 5.2mm backward and
      2.5 forward, respectively; the occlusal plane and gonial angles also increased
      nonsignificantly by 0.6 degrees  and 0.7 degrees , respectively. Upon
      investigating postoperative stability (T3-T2), Me was measured to be
      significantly 3.3mm forward and 1.4mm upward, whereas point A was measured to be
      nonsignificantly 0.5mm backward and 0.9mm upward. Therefore, the null hypothesis
      was rejected. Pearson's correlation showed that horizontal Me (T3-T2) and point A
      (T3-T2) were significantly correlated with the amounts of setback Me (T2-T1) and
      advancement A (T2-T1), respectively. In conclusion, skeletal relapses are
      significantly correlated with the amounts of mandibular setback and maxillary
      advancement.

PMID- 29196229
TI  - Chin wing: Technical note.
AB  - The chin may be concerned by morphological abnormalities in its various
      dimensions. Classical genioplasty techniques can be used to correct these but
      have some disadvantages. The "chin wing", described by Triaca, is a technique of
      genioplasty extended to the mandibular angles, considering the mandibular basilar
      border as an anatomical unit, thus achieving a better harmonious functional and
      aesthetic result. The preoperative assessment included a mandibular Cone Beam to
      evaluate the position of the inferior alveolar nerve. The procedure was performed
      under general anesthesia. The periosteal dissection was limited to the osteotomy
      area and mental nerves were protected. The osteotomy observed a modification of
      its orientation in front of the mental foramen to become parallel to the basilar
      border, which was interrupted at the level of the mandibular angle. The spaces
      created were filled with bone grafts and maintained by a symphysary plate. Chin
      wing genioplasty both improves the function and aesthetic of the face because it
      considers the mandibular basilar border as an entire anatomical unit. It can be
      performed independently of any procedure to modify the bone bases. Nowadays, chin
      wing remains a challenging technique hardly performed.

PMID- 29196230
TI  - Functional anatomy and pathophysiologic principles in mitral regurgitation: Non
      invasive assessment.
AB  - Mitral regurgitation (MR) is the most prevalent cause of valvular heart disease
      (VHD) in western countries. In the Euro Heart Survey on VHD, MR was the second
      most common heart VHD requiring surgery. It is also the most common form of VHD
      in community and population-based studies from the United States. The
      categorization of MR based on causes and mechanisms is a major determinant of
      clinical outcome, of possible therapies for the MR and of the effectiveness of
      these therapies. Surgical mitral valve (MV) repair has been shown to improve
      survival in patients with severe primary MR compared with MV replacement. In
      addition, new percutaneous repair and replacement procedures have been recently
      developed. Hence, accurate understanding of the functional anatomy of the MV and
      the pathophysiologic principles underlying MR is needed to appropriately target
      valve lesions. Recent advances in cardiac imaging have allowed to deeply
      strengthen the knowledge of the function of the MV. The present review aims at
      describing the functional anatomy and pathophysiology of MR through different
      cardiac imaging modalities.

PMID- 29196231
TI  - Metabolically healthy obese and unhealthy normal weight in Iranian adult
      population: Prevalence and the associated factors.
AB  - AIMS: The objective of this study was to determine the prevalence and the
      associated factors of metabolically unhealthy in normal-weight and metabolically
      healthy in obese. METHODS: We analyzed the data of a representative sample of 986
      participants recruited among adult population of north of Iran. Data were
      collected regarding demographic characteristics, lifestyle, body mass index,
      abdominal obesity measures, blood pressure, and lipid profiles. The participants
      were classified as metabolically healthy obese (MHO) and metabolically unhealthy
      normal-weight (MUNW). Metabolically unhealthy was defined as the presence of  >=2
      non-obese components of metabolic syndrome based on ATP III criteria. RESULTS:
      The prevalence rate of MUNW and MHO accounted for 17.2% and 15.1% respectively.
      Mean age of participants with metabolically unhealthy was significantly greater
      than metabolically healthy in both normal weight and overweight/obese (P=0.001).
      The results of multiple logistic regression analysis showed in normal-weight
      individuals, a significant association of MUNW was found with age group of 50-59
      years(OR=3.83, 95%CI: 1.71-8.57) and 60-70 years by OR=4.74(95%CI:1.79-12.54) as
      compared with age group of 20-29 years. It was also associated with current
      smoking. While metabolically healthy state in overweight/obese was inversely
      associated with age 50-59 years by OR=0.26 (95%CI:0.13-0.54) and age 60-70 years
      by OR=0.15 (95%CI:0.05- 0.39) and higher WC by OR=0.47 (95%CI:0.31-0.72) but
      positively associated with female-sex by OR=1.74 (95%CI:1.07-2.82). CONCLUSION:
      Aging and smoking are significantly associated with metabolic abnormalities in
      normal-weight while aging, abdominal obesity negatively and female positively
      associated with metabolically healthy in obese.

PMID- 29196232
TI  - Integration of microbial biopesticides in greenhouse floriculture: The Canadian
      experience.
AB  - Historically, greenhouse floriculture has relied on synthetic insecticides to
      meet its pest control needs. But, growers are increasingly faced with the loss or
      failure of synthetic chemical pesticides, declining access to new chemistries,
      stricter environmental/health and safety regulations, and the need to produce
      plants in a manner that meets the 'sustainability' demands of a consumer driven
      market. In Canada, reports of thrips resistance to spinosad (SuccessTM) within 6
      12 months of its registration prompted a radical change in pest management
      philosophy and approach. Faced with a lack of registered chemical alternatives,
      growers turned to biological control out of necessity. Biological control now
      forms the foundation for pest management programs in Canadian floriculture
      greenhouses. Success in a biocontrol program is rarely achieved through the use
      of a single agent, though. Rather, it is realized through the concurrent use of
      biological, cultural and other strategies within an integrated plant production
      system. Microbial insecticides can play a critical supporting role in
      biologically-based integrated pest management (IPM) programs. They have unique
      modes of action and are active against a range of challenging pests. As
      commercial microbial insecticides have come to market, research to generate
      efficacy data has assisted their registration in Canada, and the development and
      adaptation of integrated programs has promoted uptake by floriculture growers.
      This review documents some of the work done to integrate microbial insecticides
      into chrysanthemum and poinsettia production systems, outlines current use
      practices, and identifies opportunities to improve efficacy in Canadian
      floriculture crops.

PMID- 29196233
TI  - Microbial biopesticides for control of invertebrates: Progress from New Zealand.
AB  - Biopesticides are needed for control of endemic and invasive pests impacting New
      Zealand's primary sectors including pests that are emerging as a result of
      climate change and farming intensification. Products developed in New Zealand are
      usually based on endemic strains of microorganisms, including new species/strains
      with novel modes of action. For example, Invade and BioShield were developed
      using endemic strains of the bacterium Serratia entomophila, for use in New
      Zealand only. To date, most of these home-grown products have either struggled
      for market share or have remained in small niche markets. However, the number of
      products registered for use has been steadily increasing in response to consumer
      demand. Factors limiting past use of biopesticides in New Zealand include market
      size, registration costs and limited efficacy over a range of climatic zones.
      Many promising new agents are currently under development as biopesticides with
      international applications and the launch of several new start-up companies
      suggests a brighter future for biopesticide use in New Zealand.

PMID- 29196234
TI  - Quantitative proteomics analysis reveals alterations of lysine acetylation in
      mouse testis in response to heat shock and X-ray exposure.
AB  - Environmental stresses are important factors causing male infertility which
      attracts broad attention. Protein acetylation is a pivotal post-translational
      modification and modulates diverse physiological processes including
      spermatogenesis. In this study, we employed quantitative proteomic techniques and
      bioinformatics tools to analyze the alterations of acetylome profile of mouse
      testis after heat shock and X-irradiation. Overall, we identified 1139 lysine
      acetylation sites in 587 proteins in which 1020 lysine acetylation sites were
      quantified. The Gene Ontology analysis showed that the major acetylated protein
      groups were involved in generation of precursor metabolites and metabolic
      processes, and were localized predominantly in cytosolic and mitochondrial.
      Compared to the control group, 36 sites of 28 acetylated proteins have changed
      after heat shock, and 49 sites of 43 acetylated proteins for X-ray exposure. Some
      of the differentially acetylated proteins have been reported to be associated
      with the progression of spermatogenesis and male fertility. We observed the up
      regulated acetylation level change on testis specific histone 2B and heat shock
      protein upon heat treatment and a sharp decline of acetylation level on histone
      H2AX under X-ray treatment, suggesting their roles in male germ cells. Notably,
      the acetylation level on K279 of histone acetyltransferase (Kat7) was down
      regulated in both heat and X-ray treatments, indicating that K279 may be a key
      acetylated site and affect its functions in spermatogenesis. Our results reveal
      that protein acetylation might add another layer of complexity to the regulation
      for spermatogenesis, and further functional studies of these proteins will help
      us elucidate the mechanisms of abnormal spermatogenesis.

PMID- 29196235
TI  - Morphological features of the anterior talofibular ligament by the number of
      fiber bundles.
AB  - The aims of this study have been to clarify differences in morphological features
      based on the number of fiber bundles in the anterior talofibular ligament (ATFL),
      and to investigate the relationship between the ATFL and the calcaneofibular
      ligament (CFL). This study used 81 legs from 43 cadavers. The ATFL was classified
      according to differences in the number of fiber bundles as: Type I, with one
      fiber bundle; Type II-a, with two fiber bundles that were incompletely separated;
      Type II-b, with two fiber bundles that were completely separated; and Type III,
      with three fiber bundles. The morphological features measured were fiber bundle
      length, fiber bundle width, and fiber bundle angle. For the relationship between
      the ATFL and CFL, the positional relationship and attachment sites of the two
      ligaments were examined. Type I was present in 33%, Type II-a in 17%, Type II-b
      in 40%, and Type III in 10%. The morphological features of superior fiber bundles
      and inferior fiber bundles were significantly different within each type. Among
      types, there were significant differences in the morphological features of Type
      II-a and Type III inferior fiber bundles. In the relationship between the ATFL
      and CFL, there was a connection between the ATFL and CFL in all specimens.
      Various types were present in the positional relationship and attachment sites of
      the two ligaments. The results of this study suggest that, among different
      ligament types with two or three fiber bundles, the control function of the ankle
      may differ within each type and among types.

PMID- 29196236
TI  - Berries containing anthocyanins with enhanced methylation profiles are more
      effective at ameliorating high fat diet-induced metabolic damage.
AB  - Driven by the need for alternative whole food options to manage metabolic
      syndrome, multiple dietary interventions are suggested to achieve a better
      control of metabolic risk factors and molecular networks that regulate cellular
      energy metabolism. It is generally accepted that anthocyanin-rich diets are
      beneficial for maintaining healthy body weight, improving glucose and lipid
      metabolism, and determining inflammatory status of key metabolic tissues.
      However, anthocyanins are a structurally diverse group of phenolic compounds and
      their individual contributions to improving metabolic health are not clear. In
      this study, we show that consumption of berries containing anthocyanins with
      enhanced methylation profiles (malvidin and petunidin) is more effective at
      reducing high fat diet-induced metabolic damage in the C57BL/6 mouse model of
      polygenic obesity. Blueberries and Concord grapes (57% and 33% anthocyanins as
      malvidin, petunidin, or peonidin, respectively) improved body composition through
      individual significant effects on energy expenditure and increased activity.
      Methylated anthocyanins are also more effective at enhancing mitochondrial
      respiration and dissipation of the mitochondrial proton gradient (proton leak) in
      adipose tissue, thus counteracting mitochondrial dysfunction associated with
      metabolic stress. Together, these results provide direct proof of the higher
      protective potential of methylated anthocyanins against the metabolic
      consequences of chronic exposure to calorie-dense foods.

PMID- 29196237
TI  - Melatonin protects diabetic heart against ischemia-reperfusion injury, role of
      membrane receptor-dependent cGMP-PKG activation.
AB  - It has been demonstrated that the anti-oxidative and cardioprotective effects of
      melatonin are, at least in part, mediated by its membrane receptors. However, the
      direct downstream signaling remains unknown. We previously found that melatonin
      ameliorated myocardial ischemia-reperfusion (MI/R) injury in diabetic animals,
      although the underlying mechanisms are also incompletely understood. This study
      was designed to determine the role of melatonin membrane receptors in melatonin's
      cardioprotective actions against diabetic MI/R injury with a focus on cGMP and
      its downstream effector PKG. Streptozotocin-induced diabetic Sprague-Dawley rats
      and high-glucose medium-incubated H9c2 cardiomyoblasts were utilized to determine
      the effects of melatonin against MI/R injury. Melatonin treatment preserved
      cardiac function and reduced oxidative damage and apoptosis. Additionally,
      melatonin increased intracellular cGMP level, PKGIalpha expression, p-VASP/VASP
      ratio and further modulated myocardial Nrf-2-HO-1 and MAPK signaling. However,
      these effects were blunted by KT5823 (a selective inhibitor of PKG) or PKGIalpha
      siRNA except that intracellular cGMP level did not changed significantly.
      Additionally, our in vitro study showed that luzindole (a nonselective melatonin
      membrane receptor antagonist) or 4P-PDOT (a selective MT2 receptor antagonist)
      not only blocked the cytoprotective effect of melatonin, but also attenuated the
      stimulatory effect of melatonin on cGMP-PKGIalpha signaling and its modulatory
      effect on Nrf-2-HO-1 and MAPK signaling. This study showed that melatonin
      ameliorated diabetic MI/R injury by modulating Nrf-2-HO-1 and MAPK signaling,
      thus reducing myocardial apoptosis and oxidative stress and preserving cardiac
      function. Importantly, melatonin membrane receptors (especially MT2 receptor)
      dependent cGMP-PKGIalpha signaling played a critical role in this process.

PMID- 29196238
TI  - TGF-beta synergizes with ML264 to block IL-1beta-induced matrix degradation
      mediated by Kruppel-like factor 5 in the nucleus pulposus.
AB  - Intervertebral disc degeneration causes low back pain.Interleukin-1beta (IL
      1beta) is a well-known inflammatory mediator that is involved in disc
      degeneration but its molecular mechanisms on catabolic and anabolic events in
      nucleus pulposus (NP) cells remain unclear. Kruppel-like factor 5 (KLF5) is
      associated with inflammation and was previously shown to cause cartilage
      degradation. In this study, we revealed that KLF5 is involved in IL-1beta
      activated NF-kB cascade by enhancing both p65 phosphorylation and p65
      acetylation. Moreover, the catabolic effect of KLF5 can be abolished by
      transforming growth factor-beta (TGF-beta) via promoting the proteasomal
      degradation of KLF5. Therefore, a KLF5 inhibitor ML264 was further proved to
      synergize with TGF-beta to attenuate IL-1beta-induced intervertebral disc
      degeneration. These results indicate the critical role of KLF5 in regulating
      intervertebral disc metabolism and suggest KLF5 inhibitor such as ML264 as
      potential compound for treatment of degenerative disc disease.

PMID- 29196240
TI  - The pathophysiology of human obstructive cholestasis is mimicked in cholestatic
      Gold Syrian hamsters.
AB  - Obstructive cholestasis causes liver injury via accumulation of toxic bile acids
      (BAs). Therapeutic options for cholestatic liver disease are limited, partially
      because the available murine disease models lack translational value. Profiling
      of time-related changes following bile duct ligation (BDL) in Gold Syrian
      hamsters revealed a biochemical response similar to cholestatic patients in terms
      of BA pool composition, alterations in hepatocyte BA transport and signaling,
      suppression of BA production, and adapted BA metabolism. Hamsters tolerated
      cholestasis well for up to 28days and progressed relatively slowly to fibrotic
      liver injury. Hepatocellular necrosis was absent, which coincided with preserved
      intrahepatic energy levels and only mild oxidative stress. The histological
      response to cholestasis in hamsters was similar to the changes seen in 17
      patients with prolonged obstructive cholestasis caused by cholangiocarcinoma.
      Hamsters moreover upregulated hepatic fibroblast growth factor 15 (Fgf15)
      expression in response to BDL, which is a cytoprotective adaptation to
      cholestasis that hitherto had only been documented in cholestatic human livers.
      Hamster models should therefore be added to the repertoire of animal models used
      to study the pathophysiology of cholestatic liver disease.

PMID- 29196239
TI  - Insulin and branched-chain amino acid depletion during mouse preimplantation
      embryo culture programmes body weight gain and raised blood pressure during early
      postnatal life.
AB  - Mouse maternal low protein diet exclusively during preimplantation development
      (Emb-LPD) is sufficient to programme altered growth and cardiovascular
      dysfunction in offspring. Here, we use an in vitro model comprising
      preimplantation culture in medium depleted in insulin and branched-chain amino
      acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD
      studies, to examine the consequences for blastocyst organisation and, after
      embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to
      blastocyst stage in defined KSOM medium supplemented with four combinations of
      insulin and BCAA concentrations. Control medium contained serum insulin and
      uterine luminal fluid amino acid concentrations (including BCAA) found in control
      mothers from the maternal diet model (N-insulin+N-bcaa). Experimental medium
      (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin+N-bcaa,
      N-insulin+L-bcaa, and L-insulin+N-bcaa). Lineage-specific cell numbers of
      resultant blastocysts were not affected by treatment. Following ET, a combined
      depletion of insulin and BCAA during embryo culture induced a non sex-specific
      increase in birth weight and weight gain during early postnatal life.
      Furthermore, male offspring displayed relative hypertension and female offspring
      reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined
      depletion of metabolites also resulted in a strong positive correlation between
      body weight and glucose metabolism that was absent in the control group. Our
      results support the notion that composition of preimplantation culture medium can
      programme development and associate with disease origin affecting postnatal
      growth and cardiovascular phenotypes and implicate two important nutritional
      mediators in the inductive mechanism. Our data also have implications for human
      assisted reproductive treatment (ART) practice.

PMID- 29196241
TI  - Scleroderma skin ulcers definition, classification and treatment strategies our
      experience and review of the literature.
AB  - BACKGROUND: Skin ulcers (SU) are one of the most frequent manifestations of
      systemic sclerosis (SSc). SSc-SU are very painful, often persistent and
      recurrent; they may lead to marked impairment of patient's activities and quality
      of life. Despite their severe impact on the whole SSc patient's management, the
      proposed definition, classification criteria, and therapeutic strategies of SSc
      SU are still controversial. OBJECTIVE: The present study aimed to elaborate a
      comprehensive proposal of definition, classification, and therapeutic strategy of
      SSc-SU on the basis of our long-term single center experience along with a
      careful revision of the world literature on the same topic. METHODS: A series of
      282 SSc patients (254 females and 28 males; 84% with limited and 16% diffuse
      cutaneous SSc; mean age of 51.5+/-13.9SD at SSc onset; mean follow-up 5.8+/
      4.6SDyears) enrolled during the last decade at our Rheumatology Unit were
      retrospectively evaluated with specific attention to SSc-SU. The SSc-SU were
      classified in 5 subtypes according to prominent pathogenetic mechanism(s) and
      localization, namely 1. digital ulcers (DU) of the hands or feet, 2. SU on bony
      prominence, 3. SU on calcinosis, 4. SU of lower limbs, and 5. DU presenting with
      gangrene. This latter is a very harmful evolution of both DU of the hands and
      feet needing a differential diagnosis with critical limb ischemia. RESULTS:
      During the follow up period, one or more episodes of SSc-SU were recorded in over
      half patients (156/282, 55%); skin lesions were often recurrent and difficult-to
      heal because of local complications, mainly infections (67.3%), in some cases
      associated to osteomyelitis (19.2%), gangrene (16%), and/or amputation (11.5%).
      SSc-SU were significantly associated with lower patients' mean age at the disease
      onset (p=0.024), male gender (p=0.03), diffuse cutaneous subset (p=0.015),
      calcinosis (p=0.002), telangiectasia (p=0.008), melanodermia (p<0.001), abnormal
      PAPs (p=0.036), and/or altered inflammation reactant (CRP, p=0.001). Therapeutic
      strategy of SSc-SU included both systemic and local pharmacological treatments
      with particular attention to complicating infections and chronic/procedural pain,
      as well as a number of non-pharmacological measures. Integrated local treatments
      were often decisive for the SSc-SU healing; they were mainly based on the wound
      bed preparation principles that are summarized in the acronym TIME (necrotic
      Tissue, Infection/Inflammation, Moisture balance, and Epithelization). The
      updated review of the literature focusing on this challenging issue was analyzed
      in comparison with our experience. CONCLUSIONS: The recent advancement of
      knowledge and management strategies of SSc-SU achieved during the last years lead
      to the clear-cut improvement of patients' quality of life and reduced long-term
      disability.

PMID- 29196242
TI  - Imaging aspects of interstitial lung disease in patients with rheumatoid
      arthritis: Literature review.
AB  - OBJECTIVE: Interstitial lung disease (ILD) is a frequent and severe complication
      of rheumatoid arthritis (RA), resulting in pulmonary fibrosis (PF) and
      respiratory failure. METHODS: Chest computed tomography (CT-c) or high resolution
      CT (HRCT) is the main modality for assessment of ILD. We performed a systematic
      literature review on CT-c/HRCT findings in patients with ILD-RA, using the
      MEDLINE database for the period from 1991 to 2015. RESULTS: Findings on CT-c/HRCT
      attributed to ILD-RA are variable (ground glass opacities, reticular and nodular
      pattern, as well as a combined pattern of emphysema and PF). Correlation of CT
      c/HRCT findings with clinical data is inconsistent. CONCLUSIONS: ILD-RA is part
      of a general autoimmune inflammation and should be integrated into the decision
      making process for the treatment of RA. There is an unmet need to design an
      algorithm which will allow prediction of CT-c changes compatible with ILD-RA with
      a high probability. Hopefully, this will enable treating patients with ILD-RA
      early, with possible halting of the progression of ILD-RA toward PF.

PMID- 29196243
TI  - Clinical and immunological aspects of anti-peptidylarginine deiminase type 4
      (anti-PAD4) autoantibodies in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is the most common rheumatic autoimmune disease
      worldwide, which causes progressive joint damage and can lead to functional
      disability. Despite prominent advances in RA diagnosis and treatment during the
      last 20years, there is still a need for novel biomarkers that aid in diagnosis
      and prognosis of this heterogeneous disease. Citrullination is a key post
      translational modification implicated on anti-citrullinated protein/peptide
      antibodies (ACPA) production in RA, catalyzed by human peptidylarginine
      deiminases (PADs). Among these enzymes, PAD4 has been recognized as an important
      player in RA pathogenesis and the enzyme itself is a target of autoantibodies
      (anti-PAD4) in a subgroup of RA patients. Accumulating evidence suggests that
      anti-PAD4 autoantibodies may be useful as a severity biomarker in RA and recent
      studies have also shed light on the functional significance of these
      autoantibodies. This review summarizes the evidence on anti-PAD4 autoantibodies
      in RA, and addresses its usefulness for disease diagnosis and prognosis. Novel
      immunological aspects of anti-PAD4 antibodies and their relevance to RA
      pathogenesis are also discussed.

PMID- 29196244
TI  - A concise review of significantly modified serological biomarkers in giant cell
      arteritis, as detected by different methods.
AB  - Giant cell arteritis (GCA) is a primary systemic vasculitis present in subjects
      older than 50years with involvement of large- and medium-sized arteries. Early
      diagnosis for GCA is essential to prevent serious complications, such as
      permanent vision loss and/or cerebrovascular events. Elevated inflammatory
      cytokines, with acute phase and other proteins dominate large- and medium-sized
      arteries leading to stenosis or occlusion of arterial lumen. To date, there are
      no reliable serological markers for monitoring GCA. The review aims to provide
      concise overview of published GCA studies in order to: a) identify significantly
      changed serological biomarkers in GCA and compare the influences of techniques
      for marker evaluation and b) investigate most promising markers in GCA using
      analyte frequency and meta-analysis.

PMID- 29196245
TI  - Novel potential photodynamic therapy strategy using 5-Aminolevulinic acid for
      ovarian clear-cell carcinoma.
AB  - BACKGROUND: Photodynamic therapy (PDT) is known as a minimally invasive treatment
      for cancer. 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizing
      agent protoporphyrin IX (PpIX). Patients with ovarian clear-cell carcinoma (CCC)
      have poorer prognoses than those of patients with other histological CCC types.
      We evaluated the efficacy of ALA-PDT on CCC cells in vitro. METHODS: We used
      seven human CCC cell lines to measure the cytotoxicity of ALA-PDT. PpIX
      production in cancer cells was measured using a micro-plate reader. Quantitative
      real-time PCR was performed to assess the mRNA levels of genes involved in the
      accumulation of PpIX in cancer cells. Additionally, we measured the enhancement
      in cytotoxicity with the use of an ABCG2 inhibitor. RESULTS: We found that three
      cell lines were highly sensitive to ALA-PDT. In contrast, one cell line was
      resistant to ALA-PDT. The cytotoxicity of ALA-PDT varied among CCC cell lines.
      The IC50 values of ALA-PDT for the CCC cell lines had a wide range (30-882MUM).
      The cytotoxicity of ALA-PDT was correlated with the intracellular PpIX
      accumulation. The cell lines sensitive to ALA-PDT expressed PEPT1 (an ALA uptake
      transporter). The cell line resistant to ALA-PDT expressed ABCG2 (a PpIX export
      transporter). In the resistant cell line, a combination treatment with both ALA
      and an ABCG2 inhibitor resulted in the promotion of cytotoxic sensitivity.
      CONCLUSION: The present study revealed the efficacy of ALA-PDT against CCC with
      chemoresistance in vitro.

PMID- 29196246
TI  - Antimicrobial photodynamic activity of Rose Bengal, alone or in combination with
      Gentamicin, against planktonic and biofilm Staphylococcus aureus.
AB  - Antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy
      to antibiotics especially against superficial infections caused by bacteria
      involved in multidrug resistance processes. The aim of this study is to compare
      the efficacy of aPDT using the photosensitizer rose bengal (RB), combined or
      uncombined with gentamicin (GN), against Staphylococcus aureus. Different
      concentrations of RB (ranging from 0.03 to 64 MUg/ml) were added to S. aureus in
      water suspensions or forming biofilms in the absence or presence of GN (1-40
      MUg/ml) and the samples were irradiated (18 or 37 J/cm2). The number of viable
      bacteria was quantified by counting colony-forming units. RB-aPDT shows
      significant photoactivity. The combination of GN and RB-aPDT exerts a synergistic
      bactericidal effect against planktonic S. aureus. On the other hand, a
      synergistic effect is observed only when the maximum concentration tested of RB
      and GN was used in biofilm. According to these result the use of RB-aPDT alone or
      in combination with GN could be implemented against S. aureus.

PMID- 29196247
TI  - Early and Late Posttraumatic Epilepsy in the Setting of Traumatic Brain Injury: A
      Meta-analysis and Review of Antiepileptic Management.
AB  - BACKGROUND: Moderate to severe traumatic brain injury confers increased risk of
      posttraumatic seizures (PTSs). Early PTSs are diagnosed when seizures develop
      within 7 days after injury, whereas seizures diagnosed as late PTSs occur later.
      Patients have been treated with phenytoin (PHT) to prevent early PTSs and more
      recently with levetiracetam (LEV). Various regimens have been tried in patients
      to prevent late PTSs with variable success. We assessed and compared
      effectiveness of these drugs on early and late PTS prevention. METHODS: A
      literature search revealed 120 articles. Data were included if the same factors
      were compared across studies with identical treatment arms. Random effects models
      were used for meta-analysis to combine data into an overriding odds ratio (OR)
      comparing PTS incidence. For early PTSs, PHT was compared with placebo and LEV
      with PHT. For late PTSs, each drug was compared with placebo. RESULTS: Sixteen
      studies were included. PHT was associated with decreased odds of early seizures
      relative to placebo (OR = 0.34, 95% confidence interval [CI] 0.19-0.62). There
      was no difference in early seizure incidence between LEV and PHT (OR = 0.83, 95%
      CI 0.33-2.1). Neither LEV (OR = 0.69, 95% CI 0.24-1.96) nor PHT (OR = 0.4, 95% CI
      0.1-1.6) was associated with fewer late PTSs than placebo. CONCLUSIONS: New
      literature is consistent with current guidelines supporting antiepileptic drug
      administration for prevention of early, but not late, PTSs. With regard to early
      PTS prevention, LEV and PHT are similarly efficacious, which is consistent with
      current guidelines. Side-effect profiles favor LEV administration over PHT.

PMID- 29196248
TI  - Coagulation Factor Hyperfunction After Subarachnoid Hemorrhage Induces Deep
      Venous Thrombosis.
AB  - OBJECTIVE: To explore the change of coagulation function and associated potential
      mechanisms and the relationship between coagulation disorders and deep venous
      thrombosis (DVT) after subarachnoid hemorrhage (SAH) within 3 days of onset.
      METHODS: A total of 150 patients with SAH within 3 days of onset and 100 healthy
      individuals were recruited. Thrombelastography analysis and traditional
      laboratory tests were performed. Tissue factor (TF), tissue factor pathway
      inhibitor (TFPI) and activated protein C (APC) were tested by using enzyme-linked
      immunoassay kits. Extremities of patients with SAH were scanned by Doppler
      ultrasonography. Subgroup analysis was performed in patients with SAH based on
      the presence or lack of DVT. RESULTS: Compared with control groups, R (an
      indicator of coagulation factor function in thrombelastography) was significantly
      decreased (4.32 +/- 0.99 minutes vs. 6.00 +/- 0.75 minutes; P < 0.001),
      especially in patients with DVT. TF was significantly increased (20.84 +/- 4.15
      pg/mL vs. 5.24 +/- 1.86 pg/mL; P < 0.001). TFPI was decreased (50.42 +/- 5.81
      ng/mL vs. 64.10 +/- 6.04 ng/mL). APC had no apparent changes. R was negatively
      correlated with TF (r = 0.358; P < 0.05) and positively correlated with TFPI (r =
      0.325; P < 0.05) and APC (r = 0.162; P < 0.05). TF, TFPI, and APC had the same
      variation characteristics in the DVT subgroup compared with the no DVT subgroup.
      DVT was associated with R through association analysis (r = 0.369; P < 0.05). The
      R cutoff value for estimating the presence of DVT was 3.65 minutes. CONCLUSIONS:
      Coagulation factor hyperfunction may be mainly accompanied within 3 days of SAH
      onset and may induce DVT. This situation may be associated with TF-TFPI-APC
      imbalance. R = 3.65 minutes was a potential intervention point to prevent the
      risk of DVT in this population.

PMID- 29196249
TI  - Deep Brain Stimulation for Essential Tremor: A Comparison of Targets.
AB  - BACKGROUND: Deep brain stimulation (DBS) is an established treatment for
      refractory essential tremor (ET). Initially, the target of choice was the
      thalamic ventralis intermedius nucleus (VIM). However, the zona incerta (ZI) has
      been suggested as a superior target. Both targets are considered safe and
      effective, but a direct comparison between these targets is lacking. METHODS: We
      analyzed a single-center cohort of 44 patients with ET treated with DBS between
      1998 and 2017, targeting the VIM and/or ZI. Patient-reported outcome on the
      Washington Heights-Inwood Genetic Study of Essential Tremor rating scale, adverse
      events, and stimulation-induced side effects were assessed. RESULTS: Patient
      reported outcome of ZI DBS (-2.2 +/- 1.2; 18 patients with 28 electrodes) was
      superior to VIM DBS (-1.2 +/- 1.4; 10 patients with 19 electrodes) (P < 0.01).
      There was no difference in adverse events between implantations in VIM (45%) and
      ZI (46%). Dysarthria stimulation-induced side effects were significantly more
      often reported after VIM DBS (P = 0.01), whereas visual stimulation-induced side
      effects occurred more often after ZI DBS (P = 0.04). CONCLUSIONS: In this study,
      ZI DBS was superior to VIM DBS in terms of patient-reported effectiveness. There
      was a comparable number of complications between both targets. This finding
      further supports ZI over VIM as the principal DBS target in essential tremor.

PMID- 29196250
TI  - The Influence of Sedation Level Guided by Bispectral Index on Therapeutic Effects
      for Patients with Severe Traumatic Brain Injury.
AB  - BACKGROUND: Sedation therapy is vital for treating severe traumatic brain injury
      (TBI). Yet, types of sedation assessment tools and sedation levels that are
      suitable for sedation treatment have not been investigated. OBJECTIVE: To
      investigate the influence of different sedation levels guided by the Bispectral
      Index (BIS) on the therapeutic effects for severe TBI. METHODS: According to
      inclusion, exclusion, and rejection criteria, 35 patients were prospectively
      included and divided into Richmond Agitation Sedation Scale (RASS), BIS(I), and
      BIS(II) groups. The RASS group was controlled the level of sedation to within -2
      or -3, and the BIS(I) and (II) groups within the range of 40-50 and 50-60,
      respectively. In addition to clinical data, RASS, BIS, and intracranial pressure
      (ICP) values were collected. RASS and ICP variability were introduced to
      investigate the different of sedative control effect with or without BIS monitor,
      and the control effect of ICP between different sedation levels. Statistical
      analysis was performed to estimate the effectiveness of different sedation levels
      guided by BIS in sedation treatment within 72 hours. RESULTS: There were no
      significant differences in demographics among the 3 groups. RASS variability of
      the BIS(I) and (II) groups was significantly lower than that of the RASS group (P
      < 0.05), and in the BIS(I) group it was insignificantly lower than in the BIS(II)
      group. The ICP of the BIS(I) and (II) groups declined to <13.5 mm Hg
      significantly earlier than that of the RASS group (P < 0.05), and the difference
      between BIS(I) and (II) was insignificant. ICP variability of RASS group was
      higher than those of the BIS(I) and (II) groups (P < 0.05), and ICP variability
      of the BIS(I) group was significantly lower than that of the BIS(II) group (P <
      0.05). Differences in days in the neurosurgery intensive care unit and outcomes
      among the 3 groups were insignificant. CONCLUSIONS: BIS is more reliable than
      RASS for maintaining a stable sedation status and ICP. Deeper sedation levels
      (BIS 40-50) cause ICP to decrease more quickly, with lower ICP variability.

PMID- 29196251
TI  - Effectiveness of Ipsilateral Stroke Prevention Between Conservative Management
      and Indirect Revascularization for Moyamoya Disease in a North American Cohort.
AB  - BACKGROUND: Few reports have compared surgical intervention with conservative
      treatment for moyamoya disease (MMD) in non-Asian cohorts. This study describes
      the effectiveness of follow-up stroke prevention by indirect revascularization
      relative to conservative management in a Northeast United States study
      population. METHOD: We retrospectively reviewed records of patients with MMD at
      our institution from 1990 to 2014. Baseline characteristics and follow-up results
      including subsequent ipsilateral strokes were collected, and compared between an
      indirect revascularization group and a conservatively treated group on a per
      hemisphere basis. RESULTS: A total of 94 patients with 184 hemispheres were
      included. The average age was 23.9 +/- 18.1 years, with 76.6% (n = 141) being
      female. Racial distribution comprised white (n = 75, 40.8%), African-American (n
      = 57, 31.0%), Asian (n = 30, 16.3%), and other (n = 22, 12.0%). Eighty-three
      hemispheres (45.1%) presented with ipsilateral stroke and 54 (29.3%) with
      ipsilateral TIA. Management strategies included either conservative management
      (51.1%) or indirect bypass (48.9%). Patients who were male (P < 0.001), on
      baseline antiplatelets (P = 0.043), or with speech disturbance (P = 0.002) were
      more likely to receive indirect revascularization. Patients with headache history
      were more likely to be treated conservatively (P = 0.046). History of ipsilateral
      stroke was borderline associated with indirect bypass (P = 0.058). During a
      follow-up period of 6.37 +/- 5.81 years, the annual risk of stroke for indirect
      revascularization group was 0.93% and 2.70% for the conservative group.
      Multivariate analysis found that increasing age (P = 0.029), posterior cerebral
      artery involvement (P = 0.040), and conservative treatment (P = 0.048) were
      associated with follow-up stroke. CONCLUSION: Our results suggests that indirect
      revascularization provides symptom relief and lower risk of stroke during follow
      up compared with conservative management. Indirect revascularization should be
      considered for symptomatic MMD patients with a low surgical risk profile in a
      similar patient population.

PMID- 29196252
TI  - Atypical and Malignant Meningiomas: Neurooncologic Management in a Brazilian
      cohort.
AB  - OBJECTIVE: To analyze the surgical and oncologic treatment of a Brazilian cohort
      of patients with grade II and III meningioma at a follow-up time of 15 years to
      get an overview of these patients' outcomes. METHODS: Cross-sectional study of 43
      patients (26 women, 17 men; age range 20 to 83 years; average 57.72 +/- 14.54)
      operated on from 2000 to 2014 at a single institution, with the neuropathologic
      diagnosis of meningioma grade II (39 patients) and grade III (4 patients).
      RESULTS: Radiotherapy: 24 patients (55.81%) underwent radiotherapy; the time
      between the surgical procedure and the beginning of radiotherapy was 5 months; 7
      patients with a diagnosis of AM underwent a new surgical procedure, albeit of
      adjuvant therapy, because of tumor recurrence, and only 3 of them underwent
      radiotherapy after the first resection. Mortality: in total, 19 deaths (44.18%)
      were identified in this sample: 15 (38.46%) with GII and 4 (100%) with GIII. The
      10-year survival was expected in 35% of GII patients and 0% of GIII patients.
      CONCLUSION: Surgery is still the main form of treatment and the mainstay for
      prolonging survival. Radiotherapy is still controversial; however, we observed
      its positive impact on recurrence and progression-free survival.

PMID- 29196253
TI  - Involvement of Lypge in the formation of eye and pineal gland in zebrafish.
AB  - The proteins of Ly-6 (lymphocyte antigen-6) family are involved in the regulation
      of immunoreaction, cell migration and adhesion, and neuronal excitability.
      However, little is known about the function of Ly-6 proteins in embryogenesis.
      Herein, we identified a GPI anchored Ly-6 member named ly6 expressed in pineal
      gland and eye (lypge). Dynamic expression pattern of lypge was revealed by whole
      mount in situ hybridization. It was strikingly expressed in the pineal gland and
      cone photoreceptor, and its expression was regulated by orthodenticle homolog 5
      (otx5) which has been shown to control the expression of many pineal genes. In
      addition, we demonstrated that lypge was rhythmically expressed in larvae from
      4dpf on. Moreover, knockdown of lypge resulted in small head and small eye formed
      in zebrafish embryos. These suggest that Lypge is involved in the formation of
      the eye and pineal gland in early development of zebrafish.

PMID- 29196254
TI  - Adiponectin gene variants and decreased adiponectin plasma levels are associated
      with the risk of myocardial infarction in young age.
AB  - The aim of the study was to investigate the role of adiponectin and 5 variants of
      its gene in the risk of premature myocardial infarction (MI). The studied group
      (MI<50) consisted of 158 young patients (125 men) aged <50 with MI. The control
      groups consisted of 155 healthy people (97 men), aged <50 and 202 patients (130
      men) aged >=50 with MI (MI>=50). There were statistically significant differences
      between MI<50 patients and healthy control group in the prevalence of
      rs17300539:G>A (AA genotype: 19.3% vs. 0%, p<0.0001) and rs72563731:C>T variants
      (CC genotype: 81.5% vs. 15.9%, p<0.0001) and between MI<50 and MI>=50 patients in
      variants: rs17300539:G>A (AA genotype: 19.3% vs. 0.5%, p<0.0001), rs72563731:C>T
      (CC genotype: 82.1% vs. 60.8%, p<0.0001), rs1501299:G>T (TT genotype: 6.8% vs.
      14.9%, p=0.019) and rs822387:T>C (genotype CC: 1.5% vs. 0%, p=0.017).
      Multivariate analysis showed a significantly higher risk of MI in young CC
      carriers of rs72563731:C>T and in young AA carriers of rs17300539:G>A. Total and
      HMW adiponectin plasma levels have been significantly lower in MI<50 patients in
      comparison to MI>=50 patients (p=0.001 and p=0.001, respectively) and to healthy
      subjects (p=0.009 and p=0.01, respectively). Our study indicates the possible
      role of adiponectin and its genetic variants in MI in young age.

PMID- 29196256
TI  - Diverse responses of tanshinone biosynthesis to biotic and abiotic elicitors in
      hairy root cultures of Salvia miltiorrhiza and Salvia castanea Diels f.
      tomentosa.
AB  - Salvia miltiorrhiza (S. miltiorrhiza) and Salvia castanea Diels f. tomentosa (S.
      castanea) are both used for treatment of cardiovascular diseases. They have the
      same bioactive compound tanshinones, but whose contents are hugely different.
      This study illustrated diverse responses of tanshinone biosynthesis to yeast
      extract (YE) and Ag+ in hairy roots of the two species. YE enhanced both the
      growth and tanshinone biosynthesis of two hairy roots, and contributed more to
      tanshinone accumulation in S. castanea than that in S. miltiorrhiza. Genes
      encoding 1-deoxy-d-xylulose 5-phosphate synthase (DXS2), geranylgeranyl
      diphosphatesynthase (GGPPS1), copalyl diphosphate synthase (CPS1), and two
      cytochromes P450 (CYP76AH1 and CYP76AH3) were also more responsive to YE in S.
      castanea than those in S. miltiorrhiza. Accumulations of dihydrotanshinone I and
      tanshinone I, and most biosynthetic genes in S. miltiorrhiza were more responsive
      to Ag+ than those in S. castanea. Accumulations of dihydrotanshinone I and
      cryptotanshinone were more responsive to YE, while tanshinone IIA accumulation
      was more responsive to Ag+ in S. miltiorrhiza. However, accumulations of other
      four tanshinones and related genes in S. castanea were more responsive to YE than
      Ag+. This study provides foundations for studying diverse specialized metabolism
      between the related species.

PMID- 29196255
TI  - Hypermethylation of PGCP gene is associated with human bronchial epithelial cells
      immortalization.
AB  - Cell immortalization is the initial step for cancer development. To identify the
      differentially expressed genes regulated by DNA methylation over the course of
      human primary bronchial epithelial cell (HPBECs) immortalization, an immortalized
      HBE cell line (HBETT) was generated via introduction of an SV40 LT and a
      catalytic subunit of human telomerase reverse transcriptase (hTERT) into the
      HPBECs. Microarrays of mRNA and DNA methylation were performed to compare the
      transcriptomes and DNA methylomes between these two types of cells. The results
      from the mRNA microarray revealed many genes whose expression changed upon cell
      immortalization. We identified signatures including global hypomethylation,
      perturbation of ECM-receptor interaction, focal adhesion, and PI3K-Akt pathways
      associated with cell immortalization. Moreover, we revealed 155 differentiated
      methylation regions (DMRs) within the CpG islands (CGIs) of 42 genes and the
      perturbation of several key pathways that might be involved in HBE cell
      immortalization. Among these genes, the hypermethylation of the plasma glutamate
      carboxypeptidase (PGCP) gene appeared specifically in lung cancer tissues. The
      inhibition of PGCP expression by promoter hypermethylation was observed in both
      immortal HBETT cells and benzo[a]pyrene (Bap)-transformed HBE cells. In
      conclusion, these findings provide new insight into the epigenetic modifications
      that are critical in the transition and maintenance of cell immortalization.

PMID- 29196257
TI  - The miR-875-5p inhibits SATB2 to promote the invasion of lung cancer cells.
AB  - The pathogenesis of non-small cell lung cancer (NSCLC) is regulated by various
      miRNAs. In this study, we identified that miR-875-5pis up-regulated in NSCLC
      patients, and inhibited SATB Homeobox 2(SATB2) to promote proliferation and
      invasion of NSCLCcells.CCK-8assay revealed thatmiR-875-5p mimics promoted
      proliferation of NSCLC cells. Transwell assay showed that miR-875
      5pmimicspromoted the invasion and migration of NSCLC cells. Luciferase assays
      confirmed that miR-875-5pdirectly binds to the 3'untranslated region of SATB2,
      and western blotting showed that miR-875-5psuppresses the expression of SATB2 at
      the protein level. Moreover, the inhibitors of miR-875-5pinhibit proliferation
      and invasion of NSCLC cell lines. The miR-875-5pwouldbe a potential therapeutic
      target for NSCLC treatment in the future.

PMID- 29196258
TI  - LW-215, a newly synthesized flavonoid, exhibits potent anti-angiogenic activity
      in vitro and in vivo.
AB  - LW-215 is a newly synthesized flavonoid, which is the derivative of wogonin. Our
      group has previously confirmed that wogonin has an anti-angiogenic activity,
      while the anti-angiogenic effect of LW-215 is unclear. In this study, we explored
      whether LW-215 can inhibit angiogenesis and further probed the potential
      molecular mechanisms. We found that LW-215 inhibited migration and tube formation
      in human umbilical vein endothelial cells (HUVECs) and immortalized endothelial
      EA.hy926 cells without a significant decrease in cell viability. Microvessels
      sprouting from rat aortic ring and chicken chorioallantoic membrane (CAM) model
      also revealed that LW-215 could suppress angiogenesis in vivo. Western blot and
      ELISA analysis indicated that LW-215 could prevent VEGFR2 activation though
      reducing VEGF autocrine other than VEGFR1. Thus, its downstream kinases, such as
      Akt, ERK and p38 signaling, were inhibited. Taken together, these results fully
      showed that LW-215 might be a promising anti-angiogenesis agent.

PMID- 29196259
TI  - Arabidopsis calcium-dependent protein kinase AtCPK1 plays a positive role in
      salt/drought-stress response.
AB  - The calcium-dependent protein kinases (CDPKs) play vital roles in plant response
      to various environmental stimuli. Here, we investigated the function of
      Arabidopsis AtCPK1 in response to salt and drought stress. The loss-of-function
      cpk1 mutant displayed hypersensitive to salt and drought stress, whereas
      overexpressing AtCPK1 in Arabidopsis plants significantly enhanced the resistance
      to salt or drought stress. The reduced or elevated tolerance of cpk1 mutant and
      AtCPK1-overexpressing lines was confirmed by the changes of proline,
      malondialdehyde (MDA) and H2O2. Real-time PCR analysis revealed that the
      expression of several stress-inducible genes (RD29A, COR15A, ZAT10, APX2) down
      regulated in cpk1 mutant and up-regulated in AtCPK1-overexpressing plants. These
      results are likely to indicate that AtCPK1 positively regulates salt and drought
      stress in Arabidopsis.

PMID- 29196260
TI  - Advanced glycation end products promote triple negative breast cancer cells via
      ERK and NF-kappaB pathway.
AB  - Advanced glycation end products (AGEs) are harmful compounds generated by
      nonspecific glycation of proteins and lipids. The accumulation of AGEs is
      associated with various diseases, including breast cancer. AGEs have been shown
      to promote a breast cancer cell line by enhancing proliferation, invasion and
      migration. In this study, we investigated the effect and associated mechanism of
      AGEs on triple negative breast cancer cells. AGEs enhanced the proliferation,
      tumorigenicity, invasion and migration of primary breast cancer cells. AGEs also
      enhanced the RNA and protein expression of matrix metalloproteinase (MMP)-9 and
      its gelatinase activity. Enhanced MMP-9 expression was mediated by extracellular
      signal regulated kinase (ERK) and nuclear factor kappa B (NF-kappaB) pathways.
      Moreover, inhibitors of ERK and NF-kappaB signaling attenuated the effect of AGEs
      on tumorigenicity, invasion and migration of primary breast cancer cells. Taken
      together, we suggest that AGEs directly promote primary breast cancer cells via
      the ERK and NF-kappaB pathway, which may lead to advanced therapeutic modalities
      of breast cancer.

PMID- 29196261
TI  - A-674563 increases chondrocyte marker expression in cultured chondrocytes by
      inhibiting Sox9 degradation.
AB  - The implantation of autologous chondrocytes is a therapeutic treatment for
      articular cartilage damage. However, the benefits are limited due to the
      expansion of chondrocytes in monolayer culture, which causes loss of chondrocytic
      characters. Therefore, culture conditions that enhance chondrocytic characters
      are needed. We screened 5822 compounds and found that A-674563 enhanced the
      transcription of several chondrocyte marker genes, including Col2a1, Acan and
      Col11a2, in mouse primary chondrocytes. Experiments using cycloheximide, MG132
      and bafilomycin A1 have revealed that Sox9 is degraded through the ubiquitin
      proteasome pathway and that A-674563 inhibits this degradation, resulting in
      larger amount of Sox9 protein. RNA sequencing transcriptome analysis showed that
      A-674563 increases the expression of the gene that encodes ubiquitin-specific
      peptidase 29, which is known to induce the deubiquitination of proteins. Although
      the precise mechanism remains to be determined, our findings indicated that A
      674563 could contribute to culture conditions that expand chondrocytes without
      losing chondrocytic characters.

PMID- 29196262
TI  - Collagen VI suppresses fibronectin-induced enteric neural crest cell migration by
      downregulation of focal adhesion proteins.
AB  - The enteric nervous system (ENS) is a network of neurons and glia that are
      derived from enteric neural crest cells (ENCCs) and essential for regulating
      peristaltic activity of the colon. ENCCs migrate along the gastrointestinal tract
      to form the ENS, and disruption of ENCC motility leads to ENS disorders, such as
      Hirschsprung's disease. Previous ENCC-transplant experiments show that ENCCs can
      invade into isolated mouse intestines by age E13.5, but not after E15.5. We
      hypothesized that altered age-specific micro-environments in the intestine are
      responsible for ENCC invasion/migration. Here, we compared gene expression in the
      intestine between at E11.5 and E15.5 and identified 1355 differentially expressed
      transcripts. Among these, we found that genes encoding extracellular matrix (ECM)
      proteins were enriched. Notably, collagen VI (ColVI) family members were
      upregulated in the E15.5 mouse intestine at the mRNA and protein levels, whereas
      fibronectin (FN) was downregulated; however, both proteins showed colocalization
      at E15.5. To understand the mechanisms of ColVI and FN in ENCC migration, we
      examined neurosphere or individual ENCC-adherence capabilities toward the ECM.
      ColVI suppressed FN-induced ENCC spreading/migration, whereas ColVI induced
      morphologically narrow ENCC spreading and weak stress-fiber formation as compared
      with those with FN. Additionally, in ENCCs cultured on plates containing ColVI,
      the expression and phosphorylation of p130Cas, a members of focal adhesion
      complexes, was reduced. These data indicated an inhibitory role of ColVI in ENCC
      migration and suggested that ColVI suppression in the intestine might represent a
      novel therapeutic strategy for aganglionic colonic diseases.

PMID- 29196263
TI  - Hypothesis: Hypoxia induces de novo synthesis of NeuGc gangliosides in humans
      through CMAH domain substitute.
AB  - Immunotherapy is a growing field in cancer research. A privileged tumor
      associated antigen that has received much attention is N-glycolyl (NeuGc) GM3.
      This ganglioside is present in several types of cancer, but is almost
      undetectable in human healthy tissues. However, its non-hydroxylated variant,
      NeuAc GM3, is abundant in all mammals. Due to a deletion in the human gene
      encoding the key enzyme for synthesis of NeuGc, humans, in contrast to other
      mammals, cannot synthesize NeuGc GM3. Therefore the presence of this ganglioside
      in human cancer cells represents an enigma. It has been shown that hypoxic
      conditions trigger the expression of NeuGc gangliosides, which not only serve as
      attractive targets for cancer therapy, but also as diagnostic and prognostic
      tumor marker. Here, we confirm hypoxia-induced expression of the NeuGc GM3
      ganglioside also in HeLa cells and reveal several candidate proteins, in
      particular GM3 synthase and subunit B of respiratory complex II (SDHB), that may
      be involved in the generation of NeuGc GM3 by SILAC-based proteome analysis.
      These findings have the potential to significantly advance our understanding of
      how this enigmatic tumor-associated antigen is produced in humans, and also
      suggest a possible mechanism of action of anti-tumor antibodies that recognize
      hypoxia markers, such as 14F7.

PMID- 29196264
TI  - TR47, a PAR1-based peptide, inhibits melanoma cell migration in vitro and
      metastasis in vivo.
AB  - Activated Protein C (APC) is a serine-protease that displays antithrombotic and
      anti-inflammatory properties. In addition, cleavage of protease-activated
      receptor 1 (PAR1) by APC exerts endothelial cytoprotective actions. The effects
      of APC on endothelial cells may be reproduced by TR47, a PAR1-based peptide that
      mimics the novel N-terminus of PAR1 generated upon cleavage at Arg-46 by APC. In
      this study we demonstrate that wild-type APC and its signaling-proficient mutant,
      APC-2Cys (which has dramatically reduced anticoagulant activity), display similar
      inhibitory effects towards the transendothelial migration of A375 human melanoma
      cells. Consistent with this observation, APC and APC-2Cys significantly reduced
      the in vivo metastatic potential of the B16F10 murine melanoma cells. TR47
      recapitulated the in vitro and in vivo protective profiles of APC and APC-2Cys.
      Treatment of EA.hy926 endothelial cells with TR47 (20 MUM) significantly
      decreased the A375 cell migration. In addition, treatment of C57/BL6 mice with a
      single TR47 dose (125 MUg/animal) strongly reduced the metastatic burden of
      B16F10 cells. Together, our results suggest that protection of the endothelial
      barrier by APC/TR47-mediated signaling pathways might be a valuable therapeutic
      approach to prevent metastasis.

PMID- 29196265
TI  - Elevated O-GlcNAcylation stabilizes FOXM1 by its reduced degradation through GSK
      3beta inactivation in a human gastric carcinoma cell line, MKN45 cells.
AB  - O-GlcNAcylation is a dynamic post-translational modification of cytonuclear
      proteins for intracellular signaling. Elevated O-GlcNAcylation is a general
      feature of cancer and contributes to cancer progression, and recent studies
      indicate the contribution to increasing incidence of various types of cancer in
      diabetic patients. However, the role of O-GlcNAcylation in tumor progression is
      not fully elucidated. Forkhead box M1 (FOXM1), a master mitotic transcription
      factor, has been implicated in all major hallmarks of cancer, and is wildly
      expressed in solid tumors. Given that FOXM1 expression was reported to be
      elevated in gastric cancer, we examined the effect of high glucose or an
      inhibitor of O-GlcNAc hydrolase, Thiamet G (TMG), on FOXM1 protein expression in
      a human gastric cancer cell line, MKN45 cells, and confirmed that FOXM1 protein
      level and the cell proliferation were upregulated. To investigate the molecular
      mechanisms by which FOXM1 protein expression is regulated by O-GlcNAcylation, the
      effect of high glucose and TMG on FOXM1 ubiquitination was examined in MKN45
      cells. As a result, the ubiquitination and degradation of FOXM1 protein were both
      suppressed by high glucose and TMG treatment. However, the O-GlcNAcylation was
      not detected on FOXM1 but not on GSK-3beta. High glucose and TMG treatment
      increased phospho-serine 9 GSK-3beta, an inactive form, and the degradation of
      FOXM1 protein was suppressed by treatment of GSK-3beta inhibitors in MKN45 cells.
      Taken together, we suggest that high glucose and elevated O-GlcNAcylation
      stabilize FOXM1 protein by its reduced degradation via GSK-3beta inactivation in
      MKN45 cells, suggesting that the higher risk of gastric cancer in diabetic
      patients could be partially due to O-GlcNAcylation-mediated FOXM1 stabilization.

PMID- 29196266
TI  - TIPE2 attenuates liver fibrosis by reversing the activated hepatic stellate
      cells.
AB  - TIPE2, the tumor necrosis factor (TNF)-alpha-induced protein 8-like 2
      (TNFAIP8L2), plays an important role in regulating inflammation and immune
      homeostasis. Recent studies discovered that TIPE-2 involved in the development of
      several tumors and other proliferative diseases. The purpose of this study was to
      explore the function of TIPE-2 in the activation and proliferation in HSC-T6
      cells. Our study showed low expression of TIPE-2 in primary HSCs from CCl4
      treated mice and activated HSC-T6 cells. Functionally, over-expression of TIPE-2
      by GV141-TIPE-2 hindered the HSC-T6 cells activation and proliferation and
      expressions of beta-Catenin, Cmyc, Cyclin D1. However, inhibition TIPE-2
      expression by TIPE-2 siRNA showed the opposite effect. These observations
      revealed that TIPE-2 held a protective effect on liver fibrosis and could be a
      potential therapeutic target.

PMID- 29196267
TI  - Intrauterine exosomes are required for bovine conceptus implantation.
AB  - Exosomes, extracellular vesicles, are present in uterine flushing fluids (UFs),
      which are involved in conceptus-endometrial interactions during peri-implantation
      periods. Despite several studies on intrauterine exosomes conducted, the roles
      conceptus and endometrial exosomes play during peri-implantation periods have not
      been well characterized. To investigate the effect of bovine intrauterine
      exosomes on conceptus implantation, exosomes isolated from bovine UFs during peri
      implantation periods were subjected to global protein analysis. The analysis
      detected 596 exosomal proteins, including ruminants' pregnancy recognition factor
      IFNT, and 172 differentially expressed proteins with more than 1.5-fold changes
      in UFs on days 17, 20 and 22 pregnancy (day of conceptus implantation is
      initiated on days 19-19.5). Treatment of primary bovine endometrial epithelial
      cells with exosomes from day 17 UFs up-regulated the expression of apoptosis
      related genes, and treatment with exosomes from day 20 and 22 UFs up-regulated
      the expression of adhesion molecule. Based on these findings, intrauterine
      exosomes should be considered as an essential constituent for successful
      implantation.

PMID- 29196268
TI  - Developing 3D microscopy with CLARITY on human brain tissue: Towards a tool for
      informing and validating MRI-based histology.
AB  - Recent breakthroughs in magnetic resonance imaging (MRI) enabled quantitative
      relaxometry and diffusion-weighted imaging with sub-millimeter resolution.
      Combined with biophysical models of MR contrast the emerging methods promise in
      vivo mapping of cyto- and myelo-architectonics, i.e., in vivo histology using MRI
      (hMRI) in humans. The hMRI methods require histological reference data for model
      building and validation. This is currently provided by MRI on post mortem human
      brain tissue in combination with classical histology on sections. However, this
      well established approach is limited to qualitative 2D information, while a
      systematic validation of hMRI requires quantitative 3D information on macroscopic
      voxels. We present a promising histological method based on optical 3D imaging
      combined with a tissue clearing method, Clear Lipid-exchanged Acrylamide
      hybridized Rigid Imaging compatible Tissue hYdrogel (CLARITY), adapted for hMRI
      validation. Adapting CLARITY to the needs of hMRI is challenging due to poor
      antibody penetration into large sample volumes and high opacity of aged post
      mortem human brain tissue. In a pilot experiment we achieved transparency of up
      to 8 mm-thick and immunohistochemical staining of up to 5 mm-thick post mortem
      brain tissue by a combination of active and passive clearing, prolonged clearing
      and staining times. We combined 3D optical imaging of the cleared samples with
      tailored image processing methods. We demonstrated the feasibility for
      quantification of neuron density, fiber orientation distribution and cell type
      classification within a volume with size similar to a typical MRI voxel. The
      presented combination of MRI, 3D optical microscopy and image processing is a
      promising tool for validation of MRI-based microstructure estimates.

PMID- 29196270
TI  - EEG microstates as a tool for studying the temporal dynamics of whole-brain
      neuronal networks: A review.
AB  - The present review discusses a well-established method for characterizing resting
      state activity of the human brain using multichannel electroencephalography
      (EEG). This method involves the examination of electrical microstates in the
      brain, which are defined as successive short time periods during which the
      configuration of the scalp potential field remains semi-stable, suggesting quasi
      simultaneity of activity among the nodes of large-scale networks. A few
      prototypic microstates, which occur in a repetitive sequence across time, can be
      reliably identified across participants. Researchers have proposed that these
      microstates represent the basic building blocks of the chain of spontaneous
      conscious mental processes, and that their occurrence and temporal dynamics
      determine the quality of mentation. Several studies have further demonstrated
      that disturbances of mental processes associated with neurological and
      psychiatric conditions manifest as changes in the temporal dynamics of specific
      microstates. Combined EEG-fMRI studies and EEG source imaging studies have
      indicated that EEG microstates are closely associated with resting-state networks
      as identified using fMRI. The scale-free properties of the time series of EEG
      microstates explain why similar networks can be observed at such different time
      scales. The present review will provide an overview of these EEG microstates,
      available methods for analysis, the functional interpretations of findings
      regarding these microstates, and their behavioral and clinical correlates.

PMID- 29196271
TI  - Gibson Assembly facilitates bacterial allelic exchange mutagenesis.
AB  - Allelic exchange mutagenesis that relies on RecA-mediated homologous
      recombination up- and downstream from the targeted gene is a generalizable method
      of site-specific bacterial gene knock-out and knock-in. However, generation of a
      mutagenic DNA construct (alternative allele flanked by regions surrounding the
      gene target) and subsequent mutant selection are laborious procedures. Here we
      demonstrate allelic exchange knock-out facilitated by Gibson Assembly in
      Streptococcus iniae. Gibson Assembly allows rapid construction of a large allelic
      exchange cassette simultaneous with cloning, as well as rapid reconstruction of
      complete recombinant vector sequence when required. Additionally, we show that
      during two-step mutant selection, absence of recombination at one of the
      homologous regions (single cross-over) might be rapidly detected by colony PCR of
      meroploid clones and resolved by extension/shifting of corresponding sequence in
      DNA construct. The combination of Gibson Assembly for mutagenic DNA
      construction/redesign with colony PCR screening of meroploids to detect
      recombination at both sides of the exchange target may significantly accelerate
      generation of chromosomal mutants in a wide range of bacterial taxa.

PMID- 29196269
TI  - Diffusion MRI and MR spectroscopy reveal microstructural and metabolic brain
      alterations in chronic mild stress exposed rats: A CMS recovery study.
AB  - Chronic mild stress (CMS) induced depression elicits several debilitating
      symptoms and causes a significant economic burden on society. High variability in
      the symptomatology of depression poses substantial impediment to accurate
      diagnosis and therapy outcome. CMS exposure induces significant metabolic and
      microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC),
      caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive
      changes are limited and this may provide negative effects on the therapeutic
      treatment and management of depression. The present study utilized anhedonic rats
      from the unpredictable CMS model of depression to study metabolic recovery in the
      ventral hippocampus (vHP) and microstructural recovery in the HP, AM, CP, and
      PFC. The study employed 1H MR spectroscopy (1H MRS) and in-vivo diffusion MRI (d
      MRI) at the age of week 18 (week 1 post CMS exposure) week 20 (week 3 post CMS)
      and week 25 (week 8 post CMS exposure) in the anhedonic group, and at the age of
      week 18 and week 22 in the control group. The d-MRI data have provided an array
      of diffusion tensor metrics (FA, MD, AD, and RD), and fast kurtosis metrics (MKT,
      WL and WT). CMS exposure induced a significant metabolic alteration in vHP, and
      significant microstructural alterations were observed in the HP, AM, and PFC in
      comparison to the age match control and within the anhedonic group. A
      significantly high level of N-acetylaspartate (NAA) was observed in vHP at the
      age of week 18 in comparison to age match control and week 20 and week 25 of the
      anhedonic group. HP and AM showed significant microstructural alterations up to
      the age of week 22 in the anhedonic group. PFC showed significant microstructural
      alterations only at the age of week 18, however, most of the metrics showed
      significantly higher value at the age of week 20 in the anhedonic group. The
      significantly increased NAA concentration may indicate impaired catabolism due to
      astrogliosis or oxidative stress. The significantly increased WL in the AM and HP
      may indicate hypertrophy of AM and reduced volume of HP. Such metabolic and
      microstructural alterations could be useful in disease diagnosis and follow-up
      treatment intervention in depression and similar disorders.

PMID- 29196272
TI  - Chlamydia trachomatis antibody detection in home-collected blood samples for use
      in epidemiological studies.
AB  - Capillary blood collected in serum tubes was subjected to centrifugation delay
      while stored at room temperature. Chlamydia trachomatis (CT) IgG concentrations
      in aliquoted serum of these blood samples remained stable for seven days after
      collection. CT IgG concentrations can reliably be measured in mailed blood
      samples in epidemiological studies.

PMID- 29196273
TI  - Optimising the in vitro and in vivo performance of oral cocrystal formulations
      via spray coating.
AB  - Engineering of pharmaceutical cocrystals is an advantageous alternative to salt
      formation for improving the aqueous solubility of hydrophobic drugs. Although,
      spray drying is a well-established scale-up technique in the production of
      cocrystals, several issues can arise such as sublimation or stickiness due to low
      glass transition temperatures of some organic molecules, making the process very
      challenging. Even though, fluidised bed spray coating has been successfully
      employed in the production of amorphous drug-coated particles, to the best of our
      knowledge, it has never been employed in the production of cocrystals. The
      feasibility of this technique was proven using three model cocrystals:
      sulfadimidine (SDM)/4-aminosalicylic acid (4ASA), sulfadimidine/nicotinic acid
      (NA) and ibuprofen (IBU)/ nicotinamide (NAM). Design of experiments were
      performed to understand the critical formulation and process parameters that
      determine the formation of either cocrystal or coamorphous systems for SDM/4ASA.
      The amount and type of binder played a key role in the overall solid state and in
      vitro performance characteristics of the cocrystals. The optimal balance between
      high loading efficiencies and high degree of crystallinity was achieved only when
      a binder: cocrystal weight ratio of 5:95 or 10:90 was used. The cocrystal coated
      beads showed an improved in vitro-in vivo performance characterised by: (i) no
      tendency to aggregate in aqueous media compared to spray dried formulations, (ii)
      enhanced in vitro activity (1.8-fold greater) against S. aureus, (iii) larger
      oral absorption and bioavailability (2.2-fold higher Cmax), (iv) greater flow
      properties and (v) improved chemical stability than cocrystals produced by other
      methods derived from the morphology and solid nature of the starter cores.

PMID- 29196274
TI  - Neuromuscular diseases: Diagnosis and management.
AB  - Neuromuscular diseases (NMDs) affect the peripheral nervous system, which
      includes the motor neurons and sensory neurons; the muscle itself; or the
      neuromuscular junction. Thus, the term NMDs encompasses a vast array of different
      syndromes. Some of these syndromes are of direct relevance to paediatric
      orthopaedic surgeons, either because the presenting manifestation is a functional
      sign (e.g., toe-walking) or deformity (e.g., pes cavus or scoliosis) suggesting a
      need for orthopaedic attention or because orthopaedic abnormalities requiring
      treatment develop during the course of a known NMD. The main NMDs relevant to the
      orthopaedic surgeon are infantile spinal muscular atrophy (a motor neuron
      disease), peripheral neuropathies (chiefly, Charcot-Marie-Tooth disease),
      congenital muscular dystrophies, progressive muscular dystrophies, and Steinert
      myotonic dystrophy (or myotonic dystrophy type 1). Muscle weakness is a symptom
      shared by all these conditions. The paediatric orthopaedic surgeon must be
      familiar, not only with the musculoskeletal system, but also with many other
      domains (particularly respiratory and cardiac function and nutrition) that may
      interfere with the treatment and require preoperative management. Good knowledge
      of the natural history of each NMD is essential to ensure optimal timing of the
      therapeutic interventions, which must be performed under the best possible
      conditions in these usually frail patients. Timing is particularly crucial for
      the treatment of spinal deformities due to paraspinal muscle hypotonia during
      growth: depending on the disease and natural history, the treatment may involve
      non-operative methods or growing rods, followed by spinal fusion. A
      multidisciplinary approach is always required. Finally, the survival gains
      achieved in recent years increasingly require attention to preparing for adult
      life, to orthopaedic problems requiring treatment before the patient leaves the
      paediatric environment, and to the transition towards the adult healthcare
      system.

PMID- 29196275
TI  - Global risk mapping for major diseases transmitted by Aedes aegypti and Aedes
      albopictus.
AB  - OBJECTIVES: The objective of this study was to map the global risk of the major
      arboviral diseases transmitted by Aedes aegypti and Aedes albopictus by
      identifying areas where the diseases are reported, either through active
      transmission or travel-related outbreaks, as well as areas where the diseases are
      not currently reported but are nonetheless suitable for the vector. METHODS: Data
      relating to five arboviral diseases (Zika, dengue fever, chikungunya, yellow
      fever, and Rift Valley fever (RVF)) were extracted from some of the largest
      contemporary databases and paired with data on the known distribution of their
      vectors, A. aegypti and A. albopictus. The disease occurrence data for the
      selected diseases were compiled from literature dating as far back as 1952 to as
      recent as 2017. The resulting datasets were aggregated at the country level,
      except in the case of the USA, where state-level data were used. Spatial analysis
      was used to process the data and to develop risk maps. RESULTS: Out of the 250
      countries/territories considered, 215 (86%) are potentially suitable for the
      survival and establishment of A. aegypti and/or A. albopictus. A. albopictus has
      suitability foci in 197 countries/territories, while there are 188 that are
      suitable for A. aegypti. There is considerable variation in the suitability range
      among countries/territories, but many of the tropical regions of the world
      provide high suitability over extensive areas. Globally, 146 (58.4%)
      countries/territories reported at least one arboviral disease, while 123 (49.2%)
      reported more than one of the above diseases. The overall numbers of
      countries/territories reporting autochthonous vector-borne occurrences of Zika,
      dengue, chikungunya, yellow fever, and RVF, were 85, 111, 106, 43, and 39,
      respectively. CONCLUSIONS: With 215 countries/territories potentially suitable
      for the most important arboviral disease vectors and more than half of these
      reporting cases, arboviral diseases are indeed a global public health threat. The
      increasing proportion of reports that include multiple arboviral diseases
      highlights the expanding range of their common transmission vectors. The shared
      features of these arboviral diseases should motivate efforts to combine
      interventions against these diseases.

PMID- 29196276
TI  - Next-generation sequencing of the cerebrospinal fluid in the diagnosis of
      neurobrucellosis.
AB  - BACKGROUND: Brucellosis is the most common zoonotic infection in the world.
      Brucellosis with nervous system involvement is known as 'neurobrucellosis' (NB).
      The diagnosis of NB is difficult because its clinical manifestations are non
      specific and the sensitivity of routine culture tests is low. METHODS: Next
      generation sequencing (NGS) of cerebrospinal fluid (CSF) was used to detect
      pathogens in patients with clinically suspected central nervous system (CNS)
      infections at a tertiary referral center in China between June 1, 2016 and June
      1, 2017. The clinical characteristics and NGS results of patients with the
      diagnosis of NB were reviewed in this study. RESULTS: Four patients were rapidly
      diagnosed with NB using NGS of the CSF in patients with clinically suspected CNS
      infections, although the clinical manifestations varied dramatically between
      these patients. NGS of the CSF revealed that the sequence reads identified that
      corresponded to Brucella species ranged from 11 to 104, with genomic coverage
      ranging from 0.043% to 0.4%. Rapid diagnosis led to prompt treatment with the
      appropriate antibiotics. CONCLUSIONS: This study demonstrates the power of NGS of
      the CSF coupled with a bioinformatic pipeline in the diagnosis of NB.

PMID- 29196277
TI  - Clinical and epidemiological features of chronic Trypanosoma cruzi infection in
      patients with HIV/AIDS in Buenos Aires, Argentina.
AB  - OBJECTIVES: Trypanosoma cruzi reactivation in HIV patients is considered an
      opportunistic infection, usually with a fatal outcome. The aim of this study was
      to describe the epidemiological and clinical features of T. cruzi infection in
      HIV patients and to compare these findings between patients with and without
      Chagas disease reactivation. METHODS: The medical records of T. cruzi-HIV co
      infected patients treated at the Muniz Infectious Diseases Hospital from January
      2005 to December 2014 were reviewed retrospectively. Epidemiological and clinical
      features were assessed and compared between patients with and without Chagas
      disease reactivation. RESULTS: The medical records of 80 T. cruzi-HIV co-infected
      patients were reviewed. The most likely route of T. cruzi infection was vector
      borne (32/80 patients), followed by intravenous drug use (12/80). Nine of 80
      patients had reactivation. Patients without reactivation had a significantly
      higher CD4 T-cell count at diagnosis of T. cruzi infection (144 cells/MUl vs. 30
      cells/MUl, p=0.026). Chagas disease serology was negative in two of nine patients
      with reactivation. CONCLUSIONS: Serological assays for T. cruzi infection may be
      negative in severely immunocompromised patients. Direct parasitological
      techniques should be performed in the diagnosis of patients for whom there is a
      suspicion of T. cruzi reactivation. HIV patients with a lower CD4 count are at
      higher risk of reactivation.

PMID- 29196278
TI  - Discrepancies Between Classic and Digital Epidemiology in Searching for the
      Mayaro Virus: Preliminary Qualitative and Quantitative Analysis of Google Trends.
AB  - BACKGROUND: Mayaro virus (MAYV), first discovered in Trinidad in 1954, is spread
      by the Haemagogus mosquito. Small outbreaks have been described in the past in
      the Amazon jungles of Brazil and other parts of South America. Recently, a case
      was reported in rural Haiti. OBJECTIVE: Given the emerging importance of MAYV, we
      aimed to explore the feasibility of exploiting a Web-based tool for monitoring
      and tracking MAYV cases. METHODS: Google Trends is an online tracking system. A
      Google-based approach is particularly useful to monitor especially infectious
      diseases epidemics. We searched Google Trends from its inception (from January
      2004 through to May 2017) for MAYV-related Web searches worldwide. RESULTS: We
      noted a burst in search volumes in the period from July 2016 (relative search
      volume [RSV]=13%) to December 2016 (RSV=18%), with a peak in September 2016
      (RSV=100%). Before this burst, the average search activity related to MAYV was
      very low (median 1%). MAYV-related queries were concentrated in the Caribbean.
      Scientific interest from the research community and media coverage affected
      digital seeking behavior. CONCLUSIONS: MAYV has always circulated in South
      America. Its recent appearance in the Caribbean has been a source of concern,
      which resulted in a burst of Internet queries. While Google Trends cannot be used
      to perform real-time epidemiological surveillance of MAYV, it can be exploited to
      capture the public's reaction to outbreaks. Public health workers should be aware
      of this, in that information and communication technologies could be used to
      communicate with users, reassure them about their concerns, and to empower them
      in making decisions affecting their health.

PMID- 29196280
TI  - Search and Graph Database Technologies for Biomedical Semantic Indexing:
      Experimental Analysis.
AB  - BACKGROUND: Biomedical semantic indexing is a very useful support tool for human
      curators in their efforts for indexing and cataloging the biomedical literature.
      OBJECTIVE: The aim of this study was to describe a system to automatically assign
      Medical Subject Headings (MeSH) to biomedical articles from MEDLINE. METHODS: Our
      approach relies on the assumption that similar documents should be classified by
      similar MeSH terms. Although previous work has already exploited the document
      similarity by using a k-nearest neighbors algorithm, we represent documents as
      document vectors by search engine indexing and then compute the similarity
      between documents using cosine similarity. Once the most similar documents for a
      given input document are retrieved, we rank their MeSH terms to choose the most
      suitable set for the input document. To do this, we define a scoring function
      that takes into account the frequency of the term into the set of retrieved
      documents and the similarity between the input document and each retrieved
      document. In addition, we implement guidelines proposed by human curators to
      annotate MEDLINE articles; in particular, the heuristic that says if 3 MeSH terms
      are proposed to classify an article and they share the same ancestor, they should
      be replaced by this ancestor. The representation of the MeSH thesaurus as a graph
      database allows us to employ graph search algorithms to quickly and easily
      capture hierarchical relationships such as the lowest common ancestor between
      terms. RESULTS: Our experiments show promising results with an F1 of 69% on the
      test dataset. CONCLUSIONS: To the best of our knowledge, this is the first work
      that combines search and graph database technologies for the task of biomedical
      semantic indexing. Due to its horizontal scalability, ElasticSearch becomes a
      real solution to index large collections of documents (such as the bibliographic
      database MEDLINE). Moreover, the use of graph search algorithms for accessing
      MeSH information could provide a support tool for cataloging MEDLINE abstracts in
      real time.

PMID- 29196279
TI  - Using mHealth Technology in a Self-Management Intervention to Promote Physical
      Activity Among Adults With Chronic Disabling Conditions: Randomized Controlled
      Trial.
AB  - BACKGROUND: Physical activity is considered a comprehensive approach for managing
      limitations in physical function among adults with chronic disabling conditions.
      However, adults with chronic disabling conditions often face many barriers to
      engaging in physical activity. A strategy to promote physical activity among
      adults with chronic disabling conditions is to encourage the use of mobile health
      (mHealth) apps. OBJECTIVE: The objective of this pilot study was to examine the
      potential benefits of using commercially available mHealth apps in a self
      management intervention among 46 adults with musculoskeletal or neurological
      conditions. METHODS: Participants were randomized to one of 3 intervention
      groups: (1) mHealth-based self-management intervention, (2) paper-based self
      management intervention, and (3) contact-control intervention. Participants in
      all 3 groups met in person once and received 3 follow-up phone calls with a
      trained graduate assistant. Participants in the mHealth-based and paper-based
      groups received a computer tablet or a paper diary, respectively, to facilitate
      goal setting, self-monitoring, and action planning. Participants in the contact
      control group received information on healthy behaviors without being taught
      skills to change behaviors. The following outcomes were measured at baseline and
      at the 7th week: physical activity (Physical Activity and Disability Survey
      revised), psychosocial factors (self-efficacy, self-regulation, and social
      support), and physical function (Patient Report Outcomes Measurement Information
      System, 6-min walk test, 1-min chair stands, and 1-min arm curls). RESULTS:
      Repeated-measures multivariate analysis of variance (MANOVA) indicated
      significant differences between groups in physical activity levels (Wilks
      lambda=0.71, F6,76=2.34, P=.04). Both the mHealth-based and paper-based groups
      had large effect size increases in planned exercise and leisure-time physical
      activity compared with the contact-control group (Cohen d=1.20 and d=0.82,
      respectively). Repeated-measures MANOVA indicated nonsignificant differences
      between groups in psychosocial factors (Wilks lambda=0.85, F6,76=1.10, P=.37).
      However, both the mHealth-based and paper-based groups had moderate effect size
      improvements in self-efficacy (d=0.48 and d=0.75, respectively) and self
      regulation (d=0.59 and d=0.43, respectively) compared with the contact-control
      group. Repeated-measures MANOVA indicated nonsignificant differences between
      groups in physical function (Wilks lambda=0.94, F8,66=0.27, P=.97). There were
      small and nonsignificant changes between the mHealth-based and paper-based groups
      with regard to most outcomes. However, the mHealth-based group had moderate
      effect size increases (d=0.47) in planned exercise and leisure-time physical
      activity compared with the paper-based group. CONCLUSIONS: We found that using
      commercially available mHealth apps in a self-management intervention shows
      promise in promoting physical activity among adults with musculoskeletal and
      neurological conditions. Further research is needed to identify the best ways of
      using commercially available mobile apps in self-management interventions. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT02833311;
      https://clinicaltrials.gov/ct2/show/NCT02833311 (Archived by WebCite at
      http://www.webcitation.org/6vDVSAw1w).

PMID- 29196281
TI  - The Use of Avatar Counseling for HIV/AIDS Health Education: The Examination of
      Self-Identity in Avatar Preferences.
AB  - BACKGROUND: The number of adults using the Internet to obtain health information
      is on the rise. An estimated 66% of the adults reportedly use the Internet to
      obtain health information related to a specific disease (ie, human
      immunodeficiency virus and acquired immunodeficiency syndrome, HIV/AIDS).
      Previous research has demonstrated that health information seekers use the
      Internet to seek answers to stigma-laden questions from health avatars.
      OBJECTIVE: The objective of this study was to identify patterns in the choice of
      avatar among health information seekers (patients or public health workers) using
      the Internet to obtain HIV/AIDS information and to describe the demographic
      characteristics (age, gender, and ethnicity) of health information seekers to
      determine whether they preferred an avatar that was similar to their own gender
      and ethnicity. METHODS: The Rural South Public Health Training Center (RSPHTC)
      partnered with the New York State Department of Health to create the HIV/AIDS
      Avatar project. The avatar project was created to serve as an educational
      resource for public health workers by providing relevant and accurate information
      about HIV/AIDS. First, the user was instructed to choose one of the 8 avatars
      that voiced responses to 100 common questions and answers about HIV/AIDS. Next,
      the website gave users the option to complete a brief 3-question demographic
      survey. Finally, the demographic characteristics of each user were compared with
      the chosen avatar to determine whether they preferred an avatar that was similar
      to their own gender and ethnicity. RESULTS: The avatar project website was loaded
      with 800 videos that included the answers to the top 100 questions about HIV/AIDS
      voiced by 8 avatars. A total of 1119 Web-based health information seekers
      completed the demographic survey upon accessing the website. Of these, 55.14%
      (617/1119) users were female. A total of 49.96% (559/1119) users were aged
      between 30 and 49 years. The ethnicity of the user and the avatar was found to
      have the strongest connection. All the users choose the female avatar matching
      their own ethnicity, followed by the male avatar. Additionally, the white female
      avatar was chosen the most by all users regardless of the age group or gender.
      CONCLUSIONS: Web-based health information seekers using the Internet to access
      medical research information may feel more comfortable receiving the answers to
      HIV stigma-laden questions from avatars, rather than receiving information
      directly from a health care provider. Additionally, providers seeking to utilize
      avatars to deliver interventions in health care settings may benefit from
      offering individuals choices in how they receive health information. Having the
      ability to choose whom you seek information from may lead to an increase in
      knowledge and awareness and could motivate HIV-positive individuals to seek care.

PMID- 29196282
TI  - Reducing variations in care.

PMID- 29196283
TI  - Ringed telangiectasias: an unusual presentation of telangiectasia macularis
      eruptiva perstans.
AB  - Telangiectasia macularis eruptiva perstans (TMEP) is a rare form of cutaneous
      mastocytosis. While most cutaneous mastocytoses occur in children and are
      asymptomatic, TMEP occurs predominantly in adults and is associated with systemic
      manifestations, requiring medical management. TMEP is typically characterised by
      scattered red-brown macules on the trunk and extremities, but must be
      differentiated from other telangiectatic conditions such as scleroderma,
      hereditary haemorrhagic telangiectasia and telangiectasias secondary to
      cirrhosis. Practitioners must be aware that variants to the classic presentation
      of TMEP exist, such as the ringed telangiectasias we describe. Diagnostic workup
      including tissue biopsy must be considered in such patients after a thorough
      history and physical have been performed and other telangiectatic processes have
      been ruled out. The treatment of cutaneous mastocytosis aims at controlling
      symptoms and preventing mast cell degranulation. Cosmetic treatment includes the
      use ofPsoralen and ultraviolet A (PUVA) therapy, total skin electron beam
      radiation and flashlamp pulsed-dye laser treatment.

PMID- 29196285
TI  - Heart surgery units will stay open as long as they meet standards.

PMID- 29196284
TI  - Complete heart block as the presenting feature in subarachnoid haemorrhage.
AB  - Cardiac manifestations of subarachnoid haemorrhage (SAH) are well-documented
      phenomena that can complicate the treatment of this devastating condition. Here,
      we present a case of SAH presenting as complete heart block on initial
      assessment, an extremely rare event.A 53-year-old woman presented with a
      witnessed fall, sustaining a mild head injury. She denied any symptoms of SAH.
      Initial ECG revealed complete heart block, for which the patient was accepted
      under the cardiology team. For completion, a CT head scan was requested, this
      demonstrated significant SAH blood load in an aneurysmal rather than traumatic
      pattern. CT angiogram and subsequent digital subtraction angiography confirmed a
      posterior communicating artery aneurysm as the cause of the SAH. This case
      highlights the importance of considering neurological diagnoses in patients with
      collapse even with concomitant cardiac abnormalities, as the two are often
      inextricably linked.

PMID- 29196286
TI  - Does 'proximal control' need a new definition or a paradigm shift in exercise
      prescription? A clinical commentary.

PMID- 29196287
TI  - Denitrification by Anaeromyxobacter dehalogenans, a Common Soil Bacterium Lacking
      Nitrite Reductase Genes (nirS/nirK).
AB  - The versatile soil bacterium Anaeromyxobacter dehalogenans lacks the hallmark
      denitrification genes nirS and nirK (NO2-->NO), and couples growth to NO3-
      reduction to NH4+ (respiratory ammonification) and to N2O reduction to N2A.
      dehalogenans also grows by reducing Fe(III) to Fe(II), which chemically reacts
      with NO2- to form N2O (i.e., chemodenitrification). Following the addition of 100
      MUmoles of NO3- or NO2- to Fe(III)-grown, axenic cultures of A. dehalogenans, 54
      (+/-7) MUmoles and 113 (+/-2) MUmoles N2O-N, respectively, were produced and
      subsequently consumed. The conversion of NO3- to N2 in the presence of Fe(II)
      through linked biotic-abiotic reactions represents an unrecognized ecophysiology
      of A. dehalogenans The new findings demonstrate that the assessment of gene
      content alone is insufficient to predict microbial denitrification potential and
      N loss (i.e., the formation of gaseous N products). A survey of complete
      bacterial genomes in the NCBI Reference Sequence database coupled with available
      physiological information revealed that organisms lacking nirS/nirK but with
      Fe(III) reduction potential and genes for NO3- and N2O reduction are not rare,
      indicating that NO3- reduction to N2 through linked biotic-abiotic reactions is
      not limited to A. dehalogenans Considering the ubiquity of iron in soils and
      sediments and the broad distribution of dissimilatory Fe(III) and NO3- reducers,
      denitrification independent of NO-forming NO2- reductases (through combined
      biotic-abiotic reactions) may have substantial contributions to N loss and N2O
      flux.Importance Current attempts to gauge N loss from soils rely on the
      quantitative measurement of nirK and nirS genes and/or transcripts. In the
      presence of iron, the common soil bacterium Anaeromyxobacter dehalogenans is
      capable of denitrification and producing N2 without the key denitrification genes
      nirK/nirS Such chemodenitrifiers denitrify through combined biotic and abiotic
      reactions and have potentially large contributions to N loss to the atmosphere,
      and fill a heretofore unrecognized ecological niche in soil ecosystems. The
      findings emphasize that comprehensive understanding of N flux and accurate
      assessment of denitrification potential can only be achieved when integrated
      studies of interlinked biogeochemical cycles are performed.

PMID- 29196288
TI  - Pathway for the Biosynthesis of the Pigment Chrysogine by Penicillium
      chrysogenum.
AB  - Chrysogine is a yellow pigment produced by Penicillium chrysogenum and other
      filamentous fungi. Although the pigment was first isolated in 1973, its
      biosynthetic pathway has so far not been resolved. Here, we show that deletion of
      the highly expressed nonribosomal peptide synthetase (NRPS) gene Pc21g12630
      (chyA) resulted in a decrease in the production of chrysogine and 13 related
      compounds in the culture broth of P. chrysogenum Each of the genes of the chyA
      containing gene cluster was individually deleted, and corresponding mutants were
      examined by metabolic profiling in order to elucidate their function. The data
      suggest that the NRPS ChyA mediates the condensation of anthranilic acid and
      alanine into the intermediate 2-(2-aminopropanamido)benzoic acid, which was
      verified by feeding experiments of a DeltachyA strain with the chemically
      synthesized product. The remainder of the pathway is highly branched, yielding at
      least 13 chrysogine-related compounds.IMPORTANCEPenicillium chrysogenum is used
      in industry for the production of beta-lactams, but also produces several other
      secondary metabolites. The yellow pigment chrysogine is one of the most abundant
      metabolites in the culture broth, next to beta-lactams. Here, we have
      characterized the biosynthetic gene cluster involved in chrysogine production and
      elucidated a complex and highly branched biosynthetic pathway, assigning each of
      the chrysogine cluster genes to biosynthetic steps and metabolic intermediates.
      The work further unlocks the metabolic potential of filamentous fungi and the
      complexity of secondary metabolite pathways.

PMID- 29196289
TI  - Poly-3-Hydroxybutyrate Functionalization with BioF-Tagged Recombinant Proteins.
AB  - Polyhydroxyalkanoates (PHAs) are biodegradable polyesters that accumulate in the
      cytoplasm of certain bacteria. One promising biotechnological application
      utilizes these biopolymers as supports for protein immobilization. Here, the PHA
      binding domain of the Pseudomonas putida KT2440 PhaF phasin (BioF polypeptide)
      was investigated as an affinity tag for the in vitro functionalization of poly-3
      hydroxybutyrate (PHB) particles with recombinant proteins, namely, full-length
      PhaF and two fusion proteins tagged to BioF (BioF-C-LytA and BioF-beta
      galactosidase, containing the choline-binding module C-LytA and the beta
      galactosidase enzyme, respectively). The protein-biopolyester interaction was
      strong and stable at a wide range of pHs and temperatures, and the bound protein
      was highly protected from self-degradation, while the binding strength could be
      modulated by coating with amphiphilic compounds. Finally, BioF-beta-galactosidase
      displayed very stable enzymatic activity after several continuous activity-plus
      washing cycles when immobilized in a minibioreactor. Our results demonstrate the
      potentialities of PHA and the BioF tag for the construction of novel bioactive
      materials.IMPORTANCE Our results confirm the biotechnological potential of the
      BioF affinity tag as a versatile tool for functionalizing PHA supports with
      recombinant proteins, leading to novel bioactive materials. The wide substrate
      range of the BioF tag presumably enables protein immobilization in vitro of
      virtually all natural PHAs as well as blends, copolymers, or artificial
      chemically modified derivatives with novel physicochemical properties. Moreover,
      the strength of protein adsorption may be easily modulated by varying the coating
      of the support, providing new perspectives for the engineering of bioactive
      materials that require a tight control of protein loading.

PMID- 29196290
TI  - Evolution and Diversity of Inherited Spiroplasma Symbionts in Myrmica Ants.
AB  - Microbial partners play important roles in the biology and ecology of animals. In
      insects, maternally transmitted symbionts are especially common and can have host
      effects ranging from reproductive manipulation to nutrient provisioning and
      defense against natural enemies. In this study, we report a genus-wide
      association of Myrmica ants with the inherited bacterial symbiont Spiroplasma We
      screen Myrmica ants collected from the wild, including the invasive European fire
      ant, Myrmica rubra, and find an extraordinarily high prevalence of this symbiont
      8 of 9 species, 42 of 43 colonies, and 250 of 276 individual workers harbored
      Spiroplasma-only one host species was uninfected. In our screens, each host
      species carried a distinct Spiroplasma strain, and none were infected with more
      than one strain. All symbionts belong to the citri clade, allied most closely
      with pathogenic strains of Spiroplasma infecting corn crops and honeybees, and
      there is strong evidence of host-symbiont persistence across evolutionary time
      scales. Genome sequencing of two Spiroplasma symbionts revealed candidate genes
      that may play a part in the symbiosis, a nutrient transporter absent from other
      Spiroplasma strains, and a ribosome-inactivating protein previously implicated in
      parasite defense. These results together suggest long-term, likely mutualistic,
      relationships atypical of Spiroplasma-insect associations with potential
      significance for broad ecological interactions with MyrmicaIMPORTANCE Animal
      associated microbial symbionts can dramatically affect the biology of their
      hosts. The identification and characterization of these intimate partnerships
      remain an essential component of describing and predicting species interactions,
      especially for invasive host species. Ants perform crucial ecological functions
      as ecosystem engineers, scavengers, and predators, and ants in the genus Myrmica
      can be aggressive resource competitors and reach high densities in their native
      and invaded habitats. In this study, a novel symbiosis is identified between
      Myrmica ants and the facultative bacterial symbiont Spiroplasma Broad host
      distribution, high frequencies of infection, and host-symbiont codivergence over
      evolutionary time scales, an uncommon feature of Spiroplasma associations,
      suggest an important likely mutualistic interaction. Genome sequencing identified
      highly divergent gene candidates that may contribute to Spiroplasma's role as a
      possible defensive or nutritional partner in Myrmica.

PMID- 29196292
TI  - Gut Microbiota in Human Systemic Lupus Erythematosus and a Mouse Model of Lupus.
AB  - Gut microbiota dysbiosis has been observed in a number of autoimmune diseases.
      However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a
      prototypical autoimmune disease characterized by persistent inflammation in
      multiple organs of the body, remains elusive. Here we report the dynamics of the
      gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis
      in a small group of SLE patients with active disease. The composition of the gut
      microbiota changed markedly before and after the onset of lupus disease in NZB/W
      F1 mice, with greater diversity and increased representation of several bacterial
      species as lupus progressed from the predisease stage to the diseased stage.
      However, we did not control for age and the cage effect. Using dexamethasone as
      an intervention to treat SLE-like signs, we also found that a greater abundance
      of a group of lactobacilli (for which a species assignment could not be made) in
      the gut microbiota might be correlated with more severe disease in NZB/W F1 mice.
      Results of the human study suggest that, compared to control subjects without
      immune-mediated diseases, SLE patients with active lupus disease possessed an
      altered gut microbiota that differed in several particular bacterial species
      (within the genera Odoribacter and Blautia and an unnamed genus in the family
      Rikenellaceae) and was less diverse, with increased representation of Gram
      negative bacteria. The Firmicutes/Bacteroidetes ratios did not differ between the
      SLE microbiota and the non-SLE microbiota in our human cohort.IMPORTANCE SLE is a
      complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota
      has been reported for both mice and humans with SLE. In this emerging field,
      however, more studies are required to delineate the roles of the gut microbiota
      in different lupus-prone mouse models and people with diverse manifestations of
      SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice
      and a group of SLE patients with active disease.

PMID- 29196291
TI  - Shotgun Metagenomics and Volatilome Profile of the Microbiota of Fermented
      Sausages.
AB  - Changes in the microbial gene content and abundance can be analyzed to detect
      shifts in the microbiota composition due to the use of a starter culture in the
      food fermentation process, with the consequent shift of key metabolic pathways
      directly connected with product acceptance. Meat fermentation is a complex
      process involving microbes that metabolize the main components in meat. The
      breakdown of carbohydrates, proteins, and lipids can lead to the formation of
      volatile organic compounds (VOCs) that can drastically affect the organoleptic
      characteristics of the final products. The present meta-analysis, performed with
      the shotgun DNA metagenomic approach, focuses on studying the microbiota and its
      gene content in an Italian fermented sausage produced by using a commercial
      starter culture (a mix of Lactobacillus sakei and Staphylococcus xylosus), with
      the aim to discover the connections between the microbiota, microbiome, and the
      release of volatile metabolites during ripening. The inoculated fermentation with
      the starter culture limited the development of Enterobacteriaceae and reduced the
      microbial diversity compared to that from spontaneous fermentation. KEGG database
      genes associated with the reduction of acetaldehyde to ethanol (EC 1.1.1.1),
      acetyl phosphate to acetate (EC 2.7.2.1), and 2,3-butanediol to acetoin (EC
      1.1.1.4) were most abundant in inoculated samples (I) compared to those in
      spontaneous fermentation samples (S). The volatilome profiles were highly
      consistent with the abundance of the genes; elevated acetic acid (1,173.85
      MUg/kg), ethyl acetate (251.58 MUg/kg), and acetoin (1,100.19 MUg/kg) were
      observed in the presence of the starters at the end of fermentation. Significant
      differences were found in the liking of samples based on flavor and odor,
      suggesting a higher preference by consumers for the spontaneous fermentation
      samples. Inoculated samples exhibited the lowest scores for the liking data,
      which were clearly associated with the highest concentration of acetic
      acid.IMPORTANCE We present an advance in the understanding of meat fermentation
      by coupling DNA sequencing metagenomics and metabolomics approaches to describe
      the microbial function during this process. Very few studies using this global
      approach have been dedicated to food, and none have examined sausage
      fermentation, underlying the originality of the study. The starter culture
      drastically affected the organoleptic properties of the products. This finding
      underlines the importance of starter culture selection that takes into
      consideration the functional characteristics of the microorganism to optimize
      production efficiency and product quality.

PMID- 29196293
TI  - 3,6-Dichlorosalicylate Catabolism Is Initiated by the DsmABC Cytochrome P450
      Monooxygenase System in Rhizorhabdus dicambivorans Ndbn-20.
AB  - The degradation of the herbicide dicamba is initiated by demethylation to form
      3,6-dichlorosalicylate (3,6-DCSA) in Rhizorhabdusdicambivorans Ndbn-20. In the
      present study, a 3,6-DCSA degradation-deficient mutant, Ndbn-20m, was screened. A
      cluster, dsmR1DABCEFGR2, was lost in this mutant. The cluster consisted of nine
      genes, all of which were apparently induced by 3,6-DCSA. DsmA shared 30 to 36%
      identity with the monooxygenase components of reported three-component cytochrome
      P450 systems and formed a monophyletic branch in the phylogenetic tree. DsmB and
      DsmC were most closely related to the reported [2Fe-2S] ferredoxin and ferredoxin
      reductase, respectively. The disruption of dsmA in strain Ndbn-20 resulted in
      inactive 3,6-DCSA degradation. When dsmABC, but not dsmA alone, was introduced
      into mutant Ndbn-20m and Sphingobium quisquiliarum DC-2 (which is unable to
      degrade salicylate and its derivatives), they acquired the ability to hydroxylate
      3,6-DCSA. Single-crystal X-ray diffraction demonstrated that the DsmABC-catalyzed
      hydroxylation occurred at the C-5 position of 3,6-DCSA, generating 3,6
      dichlorogentisate (3,6-DCGA). In addition, DsmD shared 51% identity with GtdA (a
      gentisate and 3,6-DCGA 1,2-dioxygenase) from Sphingomonas sp. strain RW5.
      However, unlike GtdA, the purified DsmD catalyzed the cleavage of gentisate and 3
      chlorogentisate but not 6-chlorogentisate or 3,6-DCGA in vitro Based on the
      bioinformatic analysis and gene function studies, a possible catabolic pathway of
      dicamba in R. dicambivorans Ndbn-20 was proposed.IMPORTANCE Dicamba is widely
      used to control a variety of broadleaf weeds and is a promising target herbicide
      for the engineering of herbicide-resistant crops. The catabolism of dicamba has
      thus received increasing attention. Bacteria mineralize dicamba initially via
      demethylation, generating 3,6-dichlorosalicylate. However, the catabolism of 3,6
      dichlorosalicylate remains unknown. In this study, we cloned a gene cluster,
      dsmR1DABCEFGR2, involved in 3,6-dichlorosalicylate degradation from R.
      dicambivorans Ndbn-20, demonstrated that the cytochrome P450 monooxygenase system
      DsmABC was responsible for the 5-hydroxylation of 3,6-dichlorosalicylate, and
      proposed a dicamba catabolic pathway. This study provides a basis to elucidate
      the catabolism of dicamba and has benefits for the ecotoxicological study of
      dicamba. Furthermore, the hydroxylation of salicylate has been previously
      reported to be catalyzed by single-component flavoprotein or three-component
      Rieske non-heme iron oxygenase, whereas DsmABC was the only cytochrome P450
      monooxygenase system hydroxylating salicylate and its methyl- or chloro
      substituted derivatives.

PMID- 29196294
TI  - Enhanced Wort Fermentation with De Novo Lager Hybrids Adapted to High-Ethanol
      Environments.
AB  - Interspecific hybridization is a valuable tool for developing and improving
      brewing yeast in a number of industry-relevant aspects. However, the genomes of
      newly formed hybrids can be unstable. Here, we exploited this trait by adapting
      four brewing yeast strains, three of which were de novo interspecific lager
      hybrids with different ploidy levels, to high ethanol concentrations in an
      attempt to generate variant strains with improved fermentation performance in
      high-gravity wort. Through a batch fermentation-based adaptation process and
      selection based on a two-step screening process, we obtained eight variant
      strains which we compared to the wild-type strains in 2-liter-scale wort
      fermentations replicating industrial conditions. The results revealed that the
      adapted variants outperformed the strains from which they were derived, and the
      majority also possessed several desirable brewing-relevant traits, such as
      increased ester formation and ethanol tolerance, as well as decreased diacetyl
      formation. The variants obtained from the polyploid hybrids appeared to show
      greater improvements in fermentation performance than those derived from diploid
      strains. Interestingly, it was not only the hybrid strains, but also the
      Saccharomyces cerevisiae parent strain, that appeared to adapt and showed
      considerable changes in genome size. Genome sequencing and ploidy analysis
      revealed that changes had occurred at both the chromosome and single nucleotide
      levels in all variants. Our study demonstrates the possibility of improving de
      novo lager yeast hybrids through adaptive evolution by generating stable and
      superior variants that possess traits relevant to industrial lager beer
      fermentation.IMPORTANCE Recent studies have shown that hybridization is a
      valuable tool for creating new and diverse strains of lager yeast. Adaptive
      evolution is another strain development tool that can be applied in order to
      improve upon desirable traits. Here, we apply adaptive evolution to newly created
      lager yeast hybrids by subjecting them to environments containing high ethanol
      levels. We isolated and characterized a number of adapted variants which possess
      improved fermentation properties and ethanol tolerance. Genome analysis revealed
      substantial changes in the variants compared to the original strains. These
      improved variant strains were produced without any genetic modification and are
      suitable for industrial lager beer fermentations.

PMID- 29196295
TI  - Quasi-metagenomics and realtime sequencing aided detection and subtyping of
      Salmonella enterica from food samples.
AB  - Metagenomics analysis of food samples promises isolation-independent detection
      and subtyping of foodborne bacterial pathogens in a single workflow. Selective
      concentration of Salmonella genomic DNA through immunomagnetic separation (IMS)
      and multiple displacement amplification (MDA) were shown to shorten culture
      enrichment of Salmonella-spiked raw chicken breast samples by over 12 hours while
      permitting serotyping and high-fidelity single nucleotide polymorphisms (SNP)
      typing of the pathogen using short shotgun sequencing reads. The herein termed
      quasi-metagenomics approach was evaluated on Salmonella-spiked lettuce and black
      peppercorn samples as well as retail chicken parts naturally contaminated with
      different serotypes of Salmonella. Between 8 and 24 h culture enrichment was
      required for detecting and subtyping naturally occurring Salmonella from unspiked
      chicken parts compared with 4 to 12 h culture enrichment when Salmonella-spiked
      food samples were analyzed, indicating the likely need for longer culture
      enrichment to revive low levels of stressed or injured Salmonella cells in food.
      Further acceleration of the workflow was achieved by real-time nanopore
      sequencing. After 1.5 hours of analysis on a potable sequencer, sufficient data
      were generated from sequencing IMS-MDA product of a cultured-enriched lettuce
      sample to allow serotyping and robust phylogenetic placement of the inoculated
      isolate.Importance Both culture enrichment and next-generation sequencing remain
      to be time-consuming processes for food testing where rapid methods for pathogen
      detection are widely available. Our study demonstrated substantial acceleration
      of the respective process through IMS-MDA and real-time nanopore sequencing. In
      one example, the combined use of the two methods delivered a less than 24 h
      turnaround time from a Salmonella-contaminated lettuce sample to phylogenetic
      identification of the pathogen. Improved efficiency like this is important for
      further expanding the use of whole genome and metagenomics sequencing in
      microbial analysis of food. Our results suggest the potential of the quasi
      metagenomics approach in areas where rapid detection and subtyping of foodborne
      pathogens is important, such as foodborne outbreak response and precision
      tracking and monitoring of foodborne pathogens in production environments and
      supply chains.

PMID- 29196296
TI  - Environmental Microbiota Drives Microbial Succession and Metabolic Profiles
      during Chinese Liquor Fermentation.
AB  - Many microorganisms in environment participate in the fermentation process of
      Chinese liquor. However, it is unknown what extent of the environmental
      microbiota influences on fermentation. In this study, high-throughput sequencing
      combined with multiphasic metabolite target analysis were applied to study the
      microbial succession and metabolism changes during Chinese liquor fermentation
      from two environments (old and new workshops). SourceTracker was applied to
      evaluate the contribution of environmental microbiota to fermentation. Results
      showed that Daqu contributed 9.10-27.39% of bacterial communities and 61.06
      80.00% of fungal communities to fermentation, whereas environments (outdoor
      ground, indoor ground, tools and other unknown environments) contributed 62.61
      90.90% of bacterial communities and 20.00-38.94% of fungal communities to
      fermentation. In old workshop, six bacteria [Lactobacillus (11.73% average
      relative abundance), Bacillus (20.78%), Pseudomonas (6.13%), Kroppenstedtia
      (10.99%), Weissella (16.64%) and Pantoea (3.40%)] and five fungi [Pichia
      (55.10%), Candida (1.47%), Aspergillus (10.66%), Saccharomycopsis (22.11%) and
      Wickerhamomyces (3.35%)] were abundant at the beginning of fermentation. However,
      in new workshop, the change of environmental microbiota decreased the abundances
      of Bacillus (5.74%), Weissella (6.64%), Pichia (33.91%), Aspergillus (7.08%) and
      Wickerhamomyces (0.12%), and increased the abundances of Pseudomonas (17.04%),
      Kroppenstedtia (13.31%), Pantoea (11.41%), Acinetobacter (3.02%), Candida
      (16.47%) and Kazachstania (1.31%). Meanwhile, in new workshop, the changes of
      microbial community resulted in the increase of acetic acid, lactic acid, malic
      acid and ethyl acetate, and the decrease of ethyl lactate during fermentation.
      This study showed that environmental microbiota was an important source of
      fermentation microbiota, and could drive both the microbial succession and the
      metabolic profiles during liquor fermentation.IMPORTANCE Traditional solid-state
      fermentation of foods and beverages is mainly carried out by complex microbial
      communities from raw materials, starters and the processing environments.
      However, it is still unclear how the environmental microbiota influences on the
      quality of fermented foods and beverages, especially for Chinese liquor. In this
      study, we utilized high-throughput sequencing, microbial source tracking and
      multiphasic metabolite target analysis to analyze the origins of microbiota and
      the metabolic profiles during liquor fermentation. This study contributes to a
      deeper understanding of the role of environmental microbiota during fermentation.

PMID- 29196297
TI  - Acetylsalicylic Acid Governs the Effect of Sorafenib in RAS-Mutant Cancers.
AB  - Purpose: Identify and characterize novel combinations of sorafenib with anti
      inflammatory painkillers to target difficult-to-treat RAS-mutant
      cancer.Experimental Design: The cytotoxicity of acetylsalicylic acid (aspirin) in
      combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in
      RAS-mutant cell lines in vitro The underlying mechanism for the increased
      cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene
      knockdown. In vitro results were confirmed in RAS-mutant xenograft mouse models
      in vivoResults: The addition of aspirin but not isobutylphenylpropanoic acid
      (ibruprofen) or celecoxib (Celebrex) significantly increased the in vitro
      cytotoxicity of sorafenib. Mechanistically, combined exposure resulted in
      increased BRAF/CRAF dimerization and the simultaneous hyperactivation of the AMPK
      and ERK pathways. Combining sorafenib with other AMPK activators, such as
      metformin or A769662, was not sufficient to decrease cell viability due to sole
      activation of the AMPK pathway. The cytotoxicity of sorafenib and aspirin was
      blocked by inhibition of the AMPK or ERK pathways through shRNA or via
      pharmacologic inhibitors of RAF (LY3009120), MEK (trametinib), or AMPK (compound
      C). The combination was found to be specific for RAS/RAF-mutant cells and had no
      significant effect in RAS/RAF-wild-type keratinocytes or melanoma cells. In vivo
      treatment of human xenografts in NSG mice with sorafenib and aspirin
      significantly reduced tumor volume compared with each single-agent
      treatment.Conclusions: Combination sorafenib and aspirin exerts cytotoxicity
      against RAS/RAF-mutant cells by simultaneously affecting two independent pathways
      and represents a promising novel strategy for the treatment of RAS-mutant
      cancers. Clin Cancer Res; 24(5); 1090-102. (c)2017 AACR.

PMID- 29196299
TI  - Mrp3 Transports Clopidogrel Acyl Glucuronide from the Hepatocytes into Blood.
AB  - Clopidogrel acyl glucuronide (CLP-G) is a major phase II metabolite of
      clopidogrel generated in the liver for further excretion into urine; however, it
      is unclear whether CLP-G transports from hepatocytes into blood. Because
      multidrug resistance-associated protein 3 (MRP3) is predominantly expressed in
      the sinusoidal side of hepatocytes and preferentially transports glucuronide
      conjugates of drug metabolites from hepatocytes into bloodstream, we hypothesized
      that MRP3 could be such an efflux transporter for CLP-G. In this study, we
      compared the liver-to-plasma ratios of clopidogrel and its metabolites (including
      CLP-G) between Abcc3 (ATP-binding cassette, subfamily C, member 3) knockout (KO)
      and wild-type (WT) mice. We also evaluated the ATP-dependent uptake of
      clopidogrel and CLP-G as well as estradiol-17beta-d-glucuronide into human
      recombinant MRP3 inside-out membrane vesicles in the presence or absence of ATP.
      The results indicated that the liver-to-plasma ratio of CLP-G was 11-fold higher
      in KO mice than in WT mice, and that uptake of CLP-G (1 or 10 MUM each) into the
      membrane vesicles was 11.8- and 3.8-fold higher in the presence of ATP than in
      the presence of AMP, respectively. We conclude that Mrp3 transports CLP-G from
      the hepatocytes into blood in an ATP-dependent manner.

PMID- 29196298
TI  - Risk Assessment in Patients With Diabetes With the TIMI Risk Score for
      Atherothrombotic Disease.
AB  - OBJECTIVE: Improved risk assessment for patients with type 2 diabetes and
      elevated cardiovascular (CV) risk is needed. The Thrombolysis in Myocardial
      Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2 degrees P) predicts
      a gradient of risk in patients with prior myocardial infarction (MI) but has not
      been evaluated in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: CV
      event rates were compared by baseline TRS 2 degrees P in 16,488 patients enrolled
      in SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in
      Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53) with
      type 2 diabetes and high CV risk or established CV disease. Calibration was
      tested in the diabetes cohort from the REACH (REduction of Atherothrombosis for
      Continued Health) Registry. RESULTS: TRS 2 degrees P revealed a robust risk
      gradient for the composite of CV death, MI, and ischemic stroke in the full trial
      population, with 2-year event rates of 0.9% in the lowest- and 19.8% in the
      highest-risk groups (Ptrend < 0.001). A clear risk gradient was present within
      the subgroups of all coronary artery disease (CAD), CAD without prior MI, CAD
      with prior MI, peripheral artery disease, and prior stroke (Ptrend < 0.001 for
      each), with consistent risk relationships across subgroups. The C-statistic (0.71
      for CV death and 0.66 for the composite end point) was consistent in each
      subgroup. There was close calibration with the type 2 diabetes cohort from the
      REACH Registry (goodness-of-fit P = 0.78). CONCLUSIONS: The expanded TRS 2
      degrees P provides a practical and well-calibrated risk prediction tool for
      patients with type 2 diabetes.

PMID- 29196301
TI  - Interobserver agreement of various thyroid imaging reporting and data systems.
AB  - Ultrasonography is the best available tool for the initial work-up of thyroid
      nodules. Substantial interobserver variability has been documented in the
      recognition and reporting of some of the lesion characteristics. A number of
      classification systems have been developed to estimate the likelihood of
      malignancy: several of them have been endorsed by scientific societies, but their
      reproducibility is yet to be assessed. We evaluated the interobserver variability
      of the AACE/ACE/AME, ACR, ATA, EU-TIRADS and K-TIRADS classification systems and
      the interobserver concordance in the indication to FNA biopsy. Two raters
      independently evaluated 1055 ultrasound images of thyroid nodules identified in
      265 patients at multiple time points, in two separate sets (501 and 554 images).
      After the first set of nodules, a joint reading was performed to reach a
      consensus in the feature definitions. The interobserver agreement (Krippendorff
      alpha) in the first set of nodules was 0.47, 0.49, 0.49, 0.61 and 0.53, for
      AACE/ACE/AME, ACR, ATA, EU-TIRADS and K-TIRADS systems, respectively. The
      agreement for the indication to biopsy was substantial to near-perfect, being
      0.73, 0.61, 0.75, 0.68 and 0.82, respectively (Cohen's kappa). For all systems,
      agreement on the nodules of the second set increased. Despite the wide
      variability in the description of single ultrasonographic features, the
      classification systems may improve the interobserver agreement that further
      ameliorates after a specific training. When selecting nodules to be submitted to
      FNA biopsy, that is main purpose of these classifications, the interobserver
      agreement is substantial to almost perfect.

PMID- 29196300
TI  - Mettl3 Mutation Disrupts Gamete Maturation and Reduces Fertility in Zebrafish.
AB  - N6-methyladenosine (m6A), catalyzed by Mettl3 methyltransferase, is a highly
      conserved epigenetic modification in eukaryotic messenger RNA (mRNA). Previous
      studies have implicated m6A modification in multiple biological processes, but
      the in vivo function of m6A has been difficult to study, because mettl3 mutants
      are embryonic lethal in both mammals and plants. In this study, we have used
      transcription activator-like effector nucleases and generated viable zygotic
      mettl3 mutant, Zmettl3m/m , in zebrafish. We find that the oocytes in Zmettl3m/m
      adult females are stalled in early development and the ratio of full-grown stage
      (FG) follicles is significantly lower than that of wild type. Human chorionic
      gonadotropin-induced ovarian germinal vesicle breakdown in vitro and the numbers
      of eggs ovulated in vivo are both decreased as well, while the defects of oocyte
      maturation can be rescued by sex hormone in vitro and in vivo In Zmettl3m/m adult
      males, we find defects in sperm maturation and sperm motility is significantly
      reduced. Further study shows that 11-ketotestosterone (11-KT) and 17beta
      estradiol (E2) levels are significantly decreased in Zmettl3m/m , and defective
      gamete maturation is accompanied by decreased overall m6A modification levels and
      disrupted expression of genes critical for sex hormone synthesis and gonadotropin
      signaling in Zmettl3m/m Thus, our study provides the first in vivo evidence that
      loss of Mettl3 leads to failed gamete maturation and significantly reduced
      fertility in zebrafish. Mettl3 and m6A modifications are essential for optimal
      reproduction in vertebrates.

PMID- 29196303
TI  - Whole chromosome loss and associated breakage-fusion-bridge cycles transform
      mouse tetraploid cells.
AB  - Whole chromosome gains or losses (aneuploidy) are a hallmark of ~70% of human
      tumors. Modeling the consequences of aneuploidy has relied on perturbing spindle
      assembly checkpoint (SAC) components, but interpretations of these experiments
      are clouded by the multiple functions of these proteins. Here, we used a Cre
      recombinase-mediated chromosome loss strategy to individually delete mouse
      chromosomes 9, 10, 12, or 14 in tetraploid immortalized murine embryonic
      fibroblasts. This methodology also involves the generation of a dicentric
      chromosome intermediate, which subsequently undergoes a series of breakage-fusion
      bridge (BFB) cycles. While the aneuploid cells generally display a growth
      disadvantage in vitro, they grow significantly better in low adherence sphere
      forming conditions and three of the four lines are transformed in vivo, forming
      large and invasive tumors in immunocompromised mice. The aneuploid cells display
      increased chromosomal instability and DNA damage, a mutator phenotype associated
      with tumorigenesis in vivo Thus, these studies demonstrate a causative role for
      whole chromosome loss and the associated BFB-mediated instability in
      tumorigenesis and may shed light on the early consequences of aneuploidy in
      mammalian cells.

PMID- 29196304
TI  - Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill
      Patients with AKI.
AB  - Whether earlier initiation of RRT in critically ill patients with AKI can improve
      outcomes remains debated. We examined follow-up data from a large clinical trial
      to prospectively investigate the long-term outcomes associated with the timing of
      RRT initiation in such patients. We extended the follow-up of patients in the
      Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI
      (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%)
      patients. The primary outcome was a composite of major adverse kidney events
      (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year.
      Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and
      106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI)
      and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with
      early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45; P<
      0.001). The early initiation group had a 1-year all-cause mortality rate (56 of
      111 [50.2%]) significantly lower than that of the delayed initiation group (83 of
      119 [69.8%]; absolute difference, -19.6%; 95% CI, -32.0% to -7.2%; P<0.01). After
      1 year, 16 of 55 (29.1%) and 23 of 36 (63.9%) surviving patients in the early and
      delayed groups, respectively, failed to recover renal function (absolute
      difference, -34.8%; 95% CI, -54.6% to -15.0%; P=0.001). In conclusion, early
      initiation of RRT in these critically ill patients with AKI significantly reduced
      the occurrence of major adverse kidney events, reduced mortality, and enhanced
      renal recovery at 1 year.

PMID- 29196305
TI  - Multiple simultaneous infections in a patient with well-controlled HIV: when
      Occam's razor fails.
AB  - Multiple concurrent infectious processes have previously been reported in the
      context of advanced HIV with significant immunosuppression. Here we report a case
      of multiple infections in a 56-year-old man with well-controlled HIV diagnosed 5
      years earlier. Soon after returning to Australia following 12 years living in
      Thailand, he became unwell with fevers, night sweats, arthralgia and myalgia.
      There were no localising symptoms and examination was unremarkable.
      Investigations revealed positive syphilis (Treponema pallidum) serology with an
      RPR of 16, a positive urine culture (Klebsiella pneumoniae), a pulmonary nodule,
      a liver abscess and colitis (Entamoeba histolytica). Recovery was only complete
      when all the individual infections were treated.

PMID- 29196306
TI  - Perinatal infratentorial haemorrhage: a rare but possibly life-threatening
      condition.
AB  - BACKGROUND: Perinatal infratentorial haemorrhage (PIH) is a rare birth
      complication associated with abnormal labour. CASE PRESENTATION: A baby boy was
      born by vacuum extraction at 41 weeks' gestational age. The pregnancy was
      uneventful and Apgar scores were 3/6/9. Following initial resuscitation,
      insufficient and irregular breathing, non-reactive pupils and absence of
      spontaneous movements were noted. A diagnosis of perinatal asphyxia with hypoxic
      ischaemic encephalopathy (HIE) was considered. Therapeutic hypothermia (TH) for
      72 hours was initiated. Cerebral ultrasound showed only a mildly hyperechogenic
      periventricular substance. A brain MRI on the fourth day of life revealed a
      subdural haemorrhage in the posterior fossa with compression of the fourth
      ventricle. CONCLUSION: PIH is an important differential diagnosis to HIE that can
      be missed with ultrasound. PIH is a treatable condition but may be aggravated by
      TH. Therefore, in neonates at risk for PIH, a more detailed ultrasound protocol
      or brain MRI should be considered early.

PMID- 29196307
TI  - Methotrexate-associated lymphoproliferative disease with multiple pulmonary
      nodules in a patient with rheumatoid arthritis.
AB  - A 62-year-old woman with rheumatoid arthritis and secondary Sjogren's syndrome
      took methotrexate (MTX) 5 mg three times a week regularly but gradually developed
      an intermittent fever, oral ulcers and productive cough with mucopurulent sputum
      for about 2 weeks. Image study found multiple nodular lesions and
      lymphadenopathies in bilateral lungs. Empirical antibiotics for 1 week failed to
      alleviate the fever. A transbronchial biopsy in the right fourth bronchus showed
      infiltration of abnormally enlarged lymphoid cells with a surface marker of CD20,
      some of which also stained positively in situ with Epstein-Barr virus-encoded
      small RNA and some CD3(+) cells. After a diagnosis of MTX-associated
      lymphoproliferative disease had been made, MTX was discontinued immediately and
      intravenous methylprednisolone 125 mg/day was given for 1 week. The clinical
      condition improved dramatically within 1 month and there was no recurrence after
      3-year follow-up.

PMID- 29196308
TI  - Pseudohyponatraemia secondary to hyperlipidaemia in obstructive jaundice.
AB  - A 44-year-old man with uncontrolled diabetes and chronic pancreatitis presented
      with abdominal pain, jaundice and unintentional weight loss. Laboratory
      investigations were significant for hyponatraemia, an obstructive pattern of
      liver enzymes. Imaging was consistent with intrahepatic and extrahepatic biliary
      obstruction, and endoscopic evaluation revealed a long common bile duct
      stricture. Intravascular volume depletion, beer potomania and syndrome of
      inappropriate antidiuretic hormone (with concern for biliary or pancreatic
      malignancy) were considered in the work-up for the aetiology of the
      hyponatraemia. After 4 days of conventional treatment, hyponatraemia persisted.
      Lipid panel obtained revealed very high levels of total cholesterol. The patient
      underwent a successful biliary diversion and reconstruction surgery. Follow-up
      after 3 months showed a clinically stable patient with resolution of elevated
      liver enzymes, hyperlipidaemia and hyponatraemia. We illustrate this rare case of
      hyponatraemia secondary to hyperlipidaemia in obstructive biliary cholestasis. It
      is important for physicians to thoroughly investigate the aetiology of
      hyponatraemia at its onset.

PMID- 29196309
TI  - Low-energy atypical femoral shaft and ipsilateral neck fracture: a rare
      association.
AB  - This reports a case of a low-energy ipsilateral femoral shaft and neck fracture
      in a 69-year-old woman with vitamin D deficiency, who was taking long-term
      steroids and bisphosphonates. This is a fracture more commonly associated with a
      high-energy trauma. However, with an ageing global population and an increasing
      prevalence of bone insufficiency, we predict the incidence of this presentation
      to increase. Long-term bisphosphonate therapy has been associated with bone
      insufficiency and an increased rate of delayed union, adding to the complexity of
      management in these patients. There is currently no consensus regarding the
      choice of optimal implant or fixation technique to treat this challenging
      fracture pattern. We discuss the considerations that led to our management
      approach of a non-overlapping dynamic hip screw and femoral shaft plate construct
      which achieved uneventful bone healing and a good functional outcome within the
      first year of follow-up.

PMID- 29196310
TI  - Endovascular management of a case of spontaneous retroperitoneal haematoma
      complicated with deep vein thrombosis and pulmonary embolism.
AB  - Spontaneous retroperitoneal haematoma (SRH) can be a life-threatening emergency
      presenting with hypovolaemic shock. SRH has been rarely reported with May-Thurner
      syndrome (MTS) where it occurs due to rupture of the iliac vein or venous
      collaterals. We report a case of MTS that presented with deep venous thrombosis
      of the left lower limb complicated by bilateral pulmonary embolism (PE) and a
      large pelvic haematoma. The simultaneous occurrence of a large pelvic haematoma
      and PE offered a therapeutic challenge. Successful endovascular management of the
      case is discussed in this report.

PMID- 29196311
TI  - Unusual cause of encephalopathy after brain surgery.
AB  - For patients who have had a recent neurosurgical procedure, a visit to the
      emergency department for encephalopathy may automatically prompt a neurosurgical
      consult. We present a case of a patient with a history of Chiari malformation
      decompressed 6 months prior who presented with a 2-week history of slowly
      progressive altered mental status, headache and imbalance-symptoms consistent
      with her initial Chiari symptoms, so neurosurgery was consulted. Imaging showed
      no acute abnormality, but laboratory results revealed metabolic acidosis with
      high salicylate levels. When reporting medication use, this patient initially
      left out that she had been taking Goody's powder (845 mg aspirin) for headaches,
      and long-term use led to metabolic encephalopathy. Despite a recent history of
      surgery, it is important to keep the differential diagnosis broad especially when
      there are signs of metabolic derangement.

PMID- 29196313
TI  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is central to the
      initiation and propagation of human angiomyolipoma, suggesting its potential as a
      therapeutic target.

PMID- 29196314
TI  - Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in
      a patient with epileptic encephalopathy.

PMID- 29196316
TI  - Restoring Serotonergic Homeostasis in the Lateral Hypothalamus Rescues Sleep
      Disturbances Induced by Early-Life Obesity.
AB  - Early-life obesity predisposes to obesity in adulthood, a condition with broad
      medical implications including sleep disorders, which can exacerbate metabolic
      disturbances and disrupt cognitive and affective behaviors. In this study, we
      examined the long-term impact of transient peripubertal diet-induced obesity
      (ppDIO, induced between 4 and 10 weeks of age) on sleep-wake behavior in male
      mice. EEG and EMG recordings revealed that ppDIO increases sleep during the
      active phase but reduces resting-phase sleep quality. This impaired sleep
      phenotype persisted for up to 1 year, although animals were returned to a non
      obesiogenic diet from postnatal week 11 onwards. To better understand the
      mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on
      the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA
      expression levels of orexin and melanin-concentrating hormone, two peptides that
      are important for sleep-wake behavior and food intake. Conversely, the LH of
      ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT),
      a neurotransmitter involved in both sleep-wake and satiety regulation.
      Interestingly, an acute peripheral injection of the satiety-signaling peptide YY
      3-36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep
      disturbances, suggesting the therapeutic potential of this peptide. These
      findings provide new insights into how sleep-wake behavior is programmed during
      early life and how peripheral and central signals are integrated to coordinate
      sleep.SIGNIFICANCE STATEMENT Adult physiology and behavior are strongly
      influenced by dynamic reorganization of the brain during puberty. The present
      work shows that obesity during puberty leads to persistently dysregulated
      patterns of sleep and wakefulness by blunting serotonergic signaling in the
      lateral hypothalamus. It also shows that pharmacological mimicry of satiety with
      peptide YY3-36 can reverse this neurochemical imbalance and acutely restore sleep
      composition. These findings add insight into how innate behaviors such as feeding
      and sleep are integrated and suggest a novel mechanism through which diet-induced
      obesity during puberty imposes its long-lasting effects on sleep-wake behavior.

PMID- 29196315
TI  - Phosphorylated CCAAT/Enhancer Binding Protein beta Contributes to Rat HIV-Related
      Neuropathic Pain: In Vitro and In Vivo Studies.
AB  - Chronic pain is increasingly recognized as an important comorbidity of HIV
      infected patients, however, the exact molecular mechanisms of HIV-related pain
      are still elusive. CCAAT/enhancer binding proteins (C/EBPs) are expressed in
      various tissues, including the CNS. C/EBPbeta, one of the C/EBPs, is involved in
      the progression of HIV/AIDS, but the exact role of C/EBPbeta and its upstream
      factors are not clear in HIV pain state. Here, we used a neuropathic pain model
      of perineural HIV envelope glycoprotein gp120 application onto the rat sciatic
      nerve to test the role of phosphorylated C/EBPbeta (pC/EBPbeta) and its upstream
      pathway in the spinal cord dorsal horn (SCDH). HIV gp120 induced overexpression
      of pC/EBPbeta in the ipsilateral SCDH compared with contralateral SCDH.
      Inhibition of C/EBPbeta using siRNA against C/EBPbeta reduced mechanical
      allodynia. HIV gp120 also increased TNFalpha, TNFRI, mitochondrial superoxide
      (mtO2.-), and pCREB in the ipsilateral SCDH. ChIP-qPCR assay showed that pCREB
      enrichment on the C/EBPbeta gene promoter regions in rats with gp120 was higher
      than that in sham rats. Intrathecal TNF soluble receptor I (functionally blocking
      TNFalpha bioactivity) or knockdown of TNFRI using antisense oligodeoxynucleotide
      against TNFRI reduced mechanical allodynia, and decreased mtO2.-, pCREB and
      pC/EBPbeta. Intrathecal Mito-tempol (a mitochondria-targeted O2.-scavenger)
      reduced mechanical allodynia and decreased pCREB and pC/EBPbeta. Knockdown of
      CREB with antisense oligodeoxynucleotide against CREB reduced mechanical
      allodynia and lowered pC/EBPbeta. These results suggested that the pathway of
      TNFalpha/TNFRI-mtO2.--pCREB triggers pC/EBPbeta in the HIV gp120-induced
      neuropathic pain state. Furthermore, we confirmed the pathway using both cultured
      neurons treated with recombinant TNFalpha in vitro and repeated intrathecal
      injection of recombinant TNFalpha in naive rats. This finding provides new
      insights in the understanding of the HIV neuropathic pain mechanisms and
      treatment.SIGNIFICANCE STATEMENT Painful HIV-associated sensory neuropathy is a
      neurological complication of HIV infection. Phosphorylated C/EBPbeta (pC/EBPbeta)
      influences AIDS progression, but it is still not clear about the exact role of
      pC/EBPbeta and the detailed upstream factors of pC/EBPbeta in HIV-related pain.
      In a neuropathic pain model of perineural HIV gp120 application onto the sciatic
      nerve, we found that pC/EBPbeta was triggered by TNFalpha/TNFRI-mtO2.--pCREB
      signaling pathway. The pathway was confirmed by using cultured neurons treated
      with recombinant TNFalpha in vitro, and by repeated intrathecal injection of
      recombinant TNFalpha in naive rats. The present results revealed the functional
      significance of TNFalpha/TNFRI-mtO2.--pCREB-pC/EBPbeta signaling in HIV
      neuropathic pain, and should help in the development of more specific treatments
      for neuropathic pain.

PMID- 29196317
TI  - An Image-Based miRNA Screen Identifies miRNA-135s As Regulators of CNS Axon
      Growth and Regeneration by Targeting Kruppel-like Factor 4.
AB  - During embryonic development, axons extend over long distances to establish
      functional connections. In contrast, axon regeneration in the adult mammalian CNS
      is limited in part by a reduced intrinsic capacity for axon growth. Therefore,
      insight into the intrinsic control of axon growth may provide new avenues for
      enhancing CNS regeneration. Here, we performed one of the first miRNome-wide
      functional miRNA screens to identify miRNAs with robust effects on axon growth.
      High-content screening identified miR-135a and miR-135b as potent stimulators of
      axon growth and cortical neuron migration in vitro and in vivo in male and female
      mice. Intriguingly, both of these developmental effects of miR-135s relied in
      part on silencing of Kruppel-like factor 4 (KLF4), a well known intrinsic
      inhibitor of axon growth and regeneration. These results prompted us to test the
      effect of miR-135s on axon regeneration after injury. Our results show that
      intravitreal application of miR-135s facilitates retinal ganglion cell (RGC) axon
      regeneration after optic nerve injury in adult mice in part by repressing KLF4.
      In contrast, depletion of miR-135s further reduced RGC axon regeneration.
      Together, these data identify a novel neuronal role for miR-135s and the miR-135
      KLF4 pathway and highlight the potential of miRNAs as tools for enhancing CNS
      axon regeneration.SIGNIFICANCE STATEMENT Axon regeneration in the adult mammalian
      CNS is limited in part by a reduced intrinsic capacity for axon growth.
      Therefore, insight into the intrinsic control of axon growth may provide new
      avenues for enhancing regeneration. By performing an miRNome-wide functional
      screen, our studies identify miR-135s as stimulators of axon growth and neuron
      migration and show that intravitreal application of these miRNAs facilitates CNS
      axon regeneration after nerve injury in adult mice. Intriguingly, these
      developmental and regeneration-promoting effects rely in part on silencing of
      Kruppel-like factor 4 (KLF4), a well known intrinsic inhibitor of axon
      regeneration. Our data identify a novel neuronal role for the miR-135-KLF4
      pathway and support the idea that miRNAs can be used for enhancing CNS axon
      regeneration.

PMID- 29196319
TI  - Object Representations in Human Visual Cortex Formed Through Temporal Integration
      of Dynamic Partial Shape Views.
AB  - We typically recognize visual objects using the spatial layout of their parts,
      which are present simultaneously on the retina. Therefore, shape extraction is
      based on integration of the relevant retinal information over space. The lateral
      occipital complex (LOC) can represent shape faithfully in such conditions.
      However, integration over time is sometimes required to determine object shape.
      To study shape extraction through temporal integration of successive partial
      shape views, we presented human participants (both men and women) with artificial
      shapes that moved behind a narrow vertical or horizontal slit. Only a tiny
      fraction of the shape was visible at any instant at the same retinal location.
      However, observers perceived a coherent whole shape instead of a jumbled pattern.
      Using fMRI and multivoxel pattern analysis, we searched for brain regions that
      encode temporally integrated shape identity. We further required that the
      representation of shape should be invariant to changes in the slit orientation.
      We show that slit-invariant shape information is most accurate in the LOC.
      Importantly, the slit-invariant shape representations matched the conventional
      whole-shape representations assessed during full-image runs. Moreover, when the
      same slit-dependent shape slivers were shuffled, thereby preventing their
      spatiotemporal integration, slit-invariant shape information was reduced
      dramatically. The slit-invariant representation of the various shapes also
      mirrored the structure of shape perceptual space as assessed by perceptual
      similarity judgment tests. Therefore, the LOC is likely to mediate temporal
      integration of slit-dependent shape views, generating a slit-invariant whole
      shape percept. These findings provide strong evidence for a global encoding of
      shape in the LOC regardless of integration processes required to generate the
      shape percept.SIGNIFICANCE STATEMENT Visual objects are recognized through
      spatial integration of features available simultaneously on the retina. The
      lateral occipital complex (LOC) represents shape faithfully in such conditions
      even if the object is partially occluded. However, shape must sometimes be
      reconstructed over both space and time. Such is the case in anorthoscopic
      perception, when an object is moving behind a narrow slit. In this scenario,
      spatial information is limited at any moment so the whole-shape percept can only
      be inferred by integration of successive shape views over time. We find that LOC
      carries shape-specific information recovered using such temporal integration
      processes. The shape representation is invariant to slit orientation and is
      similar to that evoked by a fully viewed image. Existing models of object
      recognition lack such capabilities.

PMID- 29196318
TI  - Inactivation of NMDA Receptors in the Ventral Tegmental Area during Cocaine Self
      Administration Prevents GluA1 Upregulation but with Paradoxical Increases in
      Cocaine-Seeking Behavior.
AB  - Cocaine self-administration increases expression of GluA1 subunits in ventral
      tegmental area (VTA) dopamine neurons, which subsequently enhance the motivation
      for cocaine. This increase in GluA1 may be dependent on concomitant NMDA receptor
      (NMDAR) activation during self-administration, similar to cocaine-induced long
      term potentiation in the VTA. In this study, we used viral-mediated expression of
      a dominant-negative GluN1 subunit (HSV-dnGluN1) in VTA neurons to study the
      effect of transient NMDAR inactivation on the GluA1 increases induced by chronic
      cocaine self-administration in male rats. We found that dnGluN1 expression in the
      VTA limited to the 3 weeks of cocaine self-administration prevents the subsequent
      increase in tissue GluA1 levels when compared with control infusions of HSV-LacZ.
      Surprisingly, dnGluN1 expression led to an enhancement in the motivation to self
      administer cocaine as measured using a progressive ratio reinforcement schedule
      and to enhanced cocaine seeking measured in extinction/reinstatement tests
      following an extended 3 week withdrawal period. Despite blocking tissue GluA1
      increases in cocaine self-administering animals, the HSV-dnGluN1 treatment
      resulted in increased membrane levels of GluA1 and GluN2B, along with markedly
      higher locomotor responses to intra-VTA infusions of AMPA, suggesting a
      paradoxical increase in VTA AMPA receptor responsiveness. Together, these data
      suggest that NMDARs mediate cocaine-induced increases in VTA GluA1 expression,
      but such transient NMDAR inactivation also leads to compensatory scaling of
      synaptic AMPA receptors that enhance the motivational for cocaine.SIGNIFICANCE
      STATEMENT Dopamine neurons in the ventral tegmental area (VTA) are critical
      substrates of drug rewards. Animal models indicate that chronic cocaine use
      enhances excitatory glutamatergic input to these neurons, making them more
      susceptible to environmental stimuli that trigger drug craving and relapse. We
      previously found that self-administration of cocaine increases AMPA glutamate
      receptors in the VTA, and this effect enhances motivation for cocaine. Here we
      report that the mechanism for this upregulation involves NMDA receptor activity
      during cocaine use. While interference with NMDA receptor function blocks AMPA
      receptor upregulation, it also produces a paradoxical enhancement in membrane
      AMPA receptor subunits, AMPA responsiveness, and the motivation for cocaine.
      Thus, pharmacotherapy targeting NMDA receptors may inadvertently produce
      substantial adverse consequences for cocaine addiction.

PMID- 29196321
TI  - MT3-MMP Promotes Excitatory Synapse Formation by Promoting Nogo-66 Receptor
      Ectodomain Shedding.
AB  - Cell-surface molecules are dynamically regulated at the synapse to assemble and
      disassemble adhesive contacts that are important for synaptogenesis and for
      tuning synaptic transmission. Metalloproteinases dynamically regulate cellular
      behaviors through the processing of cell surface molecules. In the present study,
      we evaluated the role of membrane-type metalloproteinases (MT-MMPs) in excitatory
      synaptogenesis. We find that MT3-MMP and MT5-MMP are broadly expressed in the
      mouse cerebral cortex and that MT3-MMP loss-of-function interferes with
      excitatory synapse development in dissociated cortical neurons and in vivo We
      identify Nogo-66 receptor (NgR1) as an MT3-MMP substrate that is required for MT3
      MMP-dependent synapse formation. Introduction of the shed ectodomain of NgR1 is
      sufficient to accelerate excitatory synapse formation in dissociated cortical
      neurons and in vivo Together, our findings support a role for MT3-MMP-dependent
      shedding of NgR1 in regulating excitatory synapse development.SIGNIFICANCE
      STATEMENT In this study, we identify MT3-MMP, a membrane-bound zinc protease, to
      be necessary for the development of excitatory synapses in cortical neurons. We
      identify Nogo-66 receptors (NgR1) as a downstream target of MT3-MMP proteolytic
      activity. Furthermore, processing of surface NgR1 by MT3-MMP generates a soluble
      ectodomain fragment that accelerates the formation of excitatory synapses. We
      propose that MT3-MMP activity and NgR1 shedding could stimulate circuitry
      remodeling in the adult brain and enhance functional connectivity after brain
      injury.

PMID- 29196320
TI  - Inhibition in Simple Cell Receptive Fields Is Broad and OFF-Subregion Biased.
AB  - Inhibition in thalamorecipient layer 4 simple cells of primary visual cortex is
      believed to play important roles in establishing visual response properties and
      integrating visual inputs across their receptive fields (RFs). Simple cell RFs
      are characterized by nonoverlapping, spatially restricted subregions in which
      visual stimuli can either increase or decrease the firing rate of the cell,
      depending on contrast. Inhibition is believed to be triggered exclusively from
      visual stimulation of individual RF subregions. However, this view is at odds
      with the known anatomy of layer 4 interneurons in visual cortex and differs from
      recent findings in mouse visual cortex. Here we show with in vivo intracellular
      recordings in cats that while excitation is restricted to RF subregions,
      inhibition spans the width of simple cell RFs. Consequently, excitatory stimuli
      within a subregion concomitantly drive excitation and inhibition. Furthermore, we
      found that the distribution of inhibition across the RF is stronger toward OFF
      subregions. This inhibitory OFF-subregion bias has a functional consequence on
      spatial integration of inputs across the RF. A model based on the known anatomy
      of layer 4 demonstrates that the known proportion and connectivity of inhibitory
      neurons in layer 4 of primary visual cortex is sufficient to explain broad
      inhibition with an OFF-subregion bias while generating a variety of phase
      relations, including antiphase, between excitation and inhibition in response to
      drifting gratings.SIGNIFICANCE STATEMENT The wiring of excitatory and inhibitory
      neurons in cortical circuits is key to determining the response properties in
      sensory cortex. In the visual cortex, the first cells that receive visual input
      are simple cells in layer 4. The underlying circuitry responsible for the
      response properties of simple cells is not yet known. In this study, we challenge
      a long-held view concerning the pattern of inhibitory input and provide results
      that agree with current known anatomy. We show here that inhibition is evoked
      broadly across the receptive fields of simple cells, and we identify a surprising
      bias in inhibition within the receptive field. Our findings represent a step
      toward a unified view of inhibition across different species and sensory systems.

PMID- 29196322
TI  - A New, High-Efficacy, Noninvasive Transcranial Electric Stimulation Tuned to
      Local Neurodynamics.
AB  - In this paper, we pose the following working hypothesis: in humans, transcranial
      electric stimulation (tES) with a time course that mimics the endogenous activity
      of its target is capable of altering the target's excitability. In our case, the
      target was the primary motor cortex (M1). We identified the endogenous
      neurodynamics of hand M1's subgroups of pyramidal neuronal pools in each of our
      subjects by applying Functional Source Separation (FSS) to their EEG recordings.
      We then tested whether the corticospinal excitability of the hand representation
      under the above described stimulation, which we named transcranial individual
      neurodynamics stimulation (tIDS), was higher than in the absence of stimulation
      (baseline). As a check, we compared tIDS with the most efficient noninvasive
      facilitatory corticospinal tES known so far, which is 20 Hz transcranial
      alternating current stimulation (tACS). The control conditions were as follows:
      (1) sham, (2) transcranial random noise stimulation (tRNS) in the same frequency
      range as tIDS (1-250 Hz), and (3) a low current tIDS (tIDSlow). Corticospinal
      excitability was measured with motor-evoked potentials under transcranial
      magnetic stimulation. The mean motor-evoked potential amplitude increase was 31%
      of the baseline during tIDS (p < 0.001), and it was 15% during tACS (p = 0.096).
      tRNS, tIDSlow, and sham induced no effects. Whereas tACS did not produce an
      enhancement in any subject at the individual level, tIDS was successful in
      producing an enhancement in 8 of the 16 subjects. The results of the present
      proof-of-principle study showed that proper exploitation of local neurodynamics
      can enhance the efficacy of personalized tES.SIGNIFICANCE STATEMENT This study
      demonstrated that, in humans, transcranial individual neurodynamics stimulation
      (tIDS), which mimics the endogenous dynamics of the target neuronal pools,
      effectively changes the excitability of these pools. tIDS holds promise for high
      efficacy personalized neuromodulations based on individual local neurodynamics.

PMID- 29196323
TI  - Local Inhibition of PERK Enhances Memory and Reverses Age-Related Deterioration
      of Cognitive and Neuronal Properties.
AB  - Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of four
      known kinases that respond to cellular stress by deactivating the eukaryotic
      initiation factor 2 alpha (eIF2alpha) or other signal transduction cascades.
      Recently, both eIF2alpha and its kinases were found to play a role in normal and
      pathological brain function. Here, we show that reduction of either the amount or
      the activity of PERK, specifically in the CA1 region of the hippocampus in young
      adult male mice, enhances neuronal excitability and improves cognitive function.
      In addition, this manipulation rescues the age-dependent cellular phenotype of
      reduced excitability and memory decline. Specifically, the reduction of PERK
      expression in the CA1 region of the hippocampus of middle-aged male mice using a
      viral vector rejuvenates hippocampal function and improves hippocampal-dependent
      learning. These results delineate a mechanism for behavior and neuronal aging and
      position PERK as a promising therapeutic target for age-dependent brain
      malfunction.SIGNIFICANCE STATEMENT We found that local reduced protein kinase R
      (PKR)-like endoplasmic reticulum kinase (PERK) expression or activity in the
      hippocampus enhances neuronal excitability and cognitive function in young normal
      mice, that old CA1 pyramidal cells have reduced excitability and increased PERK
      expression that can be rescued by reducing PERK expression in the hippocampus,
      and that reducing PERK expression in the hippocampus of middle-aged mice enhances
      hippocampal-dependent learning and memory and restores it to normal performance
      levels of young mice. These findings uncover an entirely new biological link
      among PERK, neuronal intrinsic properties, aging, and cognitive function.
      Moreover, our findings propose a new way to fight mild cognitive impairment and
      aging-related cognitive deterioration.

PMID- 29196324
TI  - Mitochondrial permeability transition, F1FO-ATPase and calcium: an enigmatic
      triangle.

PMID- 29196325
TI  - Confronting the Opioid Epidemic: How Dental Schools Can Lead.

PMID- 29196327
TI  - Oral Health Care Quality Measurement and Its Role in Dental Education.
AB  - Concerns about health care quality have affected much of the health care delivery
      system including dentistry and dental education. Believing measurement is the key
      element in improving quality, the Dental Quality Alliance brought together major
      stakeholders in oral health care to lead the development of oral health
      performance measures that can be used to evaluate the performance of dental
      programs and practices. These measures complement the quality assurance measures
      dental schools use to ensure compliance with accreditation standards on patient
      care delivery. This article describes the rationale for and process of developing
      these performance measures and argues that dental schools should implement
      quality measurement processes in their clinical programs to improve the clinical
      practices of the present and better prepare their graduates for their practices
      of the future.

PMID- 29196326
TI  - Massachusetts Dental Schools Respond to the Prescription Opioid Crisis: A
      Statewide Collaboration.
AB  - The prescription opioid crisis has involved all sectors of U.S. society,
      affecting every community, socioeconomic group, and age group. While federal and
      state agencies are actively working to deal with the epidemic, medical and dental
      providers have been tasked to increase their awareness of the issues and consider
      ways to safely prescribe opioids and, at the same time, effectively treat their
      patients' pain. The Commonwealth of Massachusetts, under the leadership of
      Governor Charles D. Baker and his administration, challenged the state's four
      medical schools and three dental schools to improve their curricula to prepare
      the next generation of clinicians to deal with this crisis in an evidence-based,
      effective, and sympathetic way. This Perspectives article outlines the national
      prescription opioid crisis, details its effects in Massachusetts, and describes
      the interdisciplinary collaboration among the Commonwealth, the three dental
      schools, the Massachusetts Dental Society, and a concerned student group. The
      article also describes the efforts each dental school is undertaking as well as
      an assessment of the challenges and limitations in implementing the initiative.
      The authors hope that the Massachusetts model will be a useful resource for
      dental schools in other states.

PMID- 29196328
TI  - An Interprofessional Education and Collaborative Practice Model for Dentistry and
      Pharmacy.
AB  - The aims of this study were to evaluate the feasibility of an interprofessional
      education and collaborative practice model (IECPM) developed by the School of
      Dentistry (SOD) and College of Pharmacy (COP) for the University of Minnesota
      dental clinics and to report results of the needs assessment using specific
      primary care metrics and medication histories gathered through use of the model
      in 2015-16. Planning focused on establishing a workflow to implement the IECPM by
      the SOD and COP. The interprofessional team that provided patient care for the
      study consisted of 50 dental students, ten dental therapy students, one pharmacy
      student, one pharmacy resident, one faculty pharmacist, one dental assistant, one
      faculty dental hygienist, and two dentists. The team selected 190 patients in the
      SOD clinic for the study based on the inclusion criteria: patients with two or
      more chronic medical conditions who were taking medications. The 190 patients
      received a comprehensive dental exam, review of social and medical history, and
      medication therapy management assessment by the interprofessional team. Specific
      core primary care metrics (blood pressure, pulse, tobacco use, and diabetes
      status) and identification of drug therapy problems (DTPs) were monitored and/or
      screened for during the dental visit. The results showed that the IECPM helped
      identify that this cohort of patients presented with chronic conditions: 64% had
      hypertension, 34% had diabetes, and 10.5% reported smoking cigarettes. Several
      DTPs were identified, of which "needs additional drug therapy" was the most
      common. This cohort was taking multiple medications (2-34 per patient) to address
      a variety of medical conditions. The study concluded that the IECPM with the SOD
      and COP helped address a primary care need that often goes unmet in dental
      clinics.

PMID- 29196329
TI  - Changing Health Professionals' Attitudes and Practice Behaviors Through
      Interprofessional Continuing Education in Oral-Systemic Health.
AB  - Integration of oral-systemic science into clinical care holds promise for
      improving patient outcomes and presenting opportunities for individuals in
      various health care professions to learn with, from, and about each other. The
      aim of this study was to examine whether an interprofessional continuing
      education program dedicated to oral-systemic health improved participants'
      attitudes toward interprofessional education and collaboration between dental and
      non-dental health care professionals and whether it influenced the physicians'
      practice of screening for debilitating oral diseases. The study took place in
      2014 and used a mixed-methods approach, consisting of Readiness for
      Interprofessional Learning Scale (RIPLS) surveys conducted before, immediately
      after, and six months after the intervention, as well as surveys of self-reported
      practice behaviors and semi-structured interviews. A total of 231 health care
      professionals participated in the lectures and roundtable discussions. Of those,
      134 responded to the pre-program survey (58% response rate), 110 responded to the
      post-program survey (48% response rate), and 58 responded to the survey six
      months after the program (25% response rate). The participants' median total
      RIPLS score at baseline was 76.5, which increased significantly immediately
      following the program (81.0) but returned to baseline six months later (76.5).
      Participants' RIPLS domain scores also increased significantly by profession from
      before to after the event, with effects returning to baseline after six months.
      Significantly more physicians reported screening for caries and periodontal
      disease after the intervention. An overall theme of "learning with, from, and
      about each other" was drawn from the interviews with 15 participants. The
      physicians took away a message of "just look in the mouth," while the dental
      professionals reported feeling valued as members of the health care team.
      Although reported improvements in oral-systemic health practice immediately after
      the intervention were encouraging, further research is necessary to understand
      why collaborative behaviors were not sustained.

PMID- 29196330
TI  - Dental Students' Study Habits in Flipped/Blended Classrooms and Their Association
      with Active Learning Practices.
AB  - In recognition of the importance for dental education programs to take a student
      centered approach in which students are encouraged to take responsibility for
      their learning, a pediatric dentistry course redesign aimed at promoting greater
      active and self-directed learning was implemented at one U.S. dental school. The
      aim of this study was to examine the association between the students' self
      reported study habits and active learning practices necessary for meaningful
      learning in the flipped/blended classroom. A convenience sample of two classes of
      second-year dental students in spring 2014 (SP14, n=106) and spring 2015 (SP15,
      n=106) was invited to participate in the study. Of the SP14 students, 84
      participated, for a response rate of 79%; of the SP15 students, 94 participated,
      for a response rate of 87%. Students' self-reported responses to questions about
      study strategies with the prerecorded lecture materials and assigned reading
      materials were examined. Non-parametric analyses resulted in a cohort effect, so
      data are reported by class. In the SP15 class, 72% reported watching all/more
      than half of the prerecorded lectures versus 62% of the SP14 class, with a
      majority watching more than one lecture per week. In the SP15 cohort, 68% used
      active learning strategies when watching the lectures versus 58.3% of the SP14
      cohort. The time of day preferred by the majority of both cohorts for interacting
      with course materials was 7-11 pm. Both SP14 and SP15 students reported being
      unlikely to read assigned materials prior to coming to class. Overall, the course
      redesign appeared to engage students in self-directed active learning. However,
      the degree to which active learning practices were taking place to achieve
      meaningful learning was questionable given students' self-reported study
      strategies. More work is needed to examine strategies for promoting study
      practices that will lead to meaningful learning.

PMID- 29196331
TI  - Is Dental Students' Clinical Productivity Associated with Their Personality
      Profile?
AB  - The aim of this study was to assess the relationship between personality
      preferences of incoming fourth-year dental students at the University of Texas
      Health Science Center at San Antonio as measured by the Keirsey Temperament
      Sorter II and their third-year clinical productivity and percentage of broken
      appointments. All 105 incoming fourth-year dental students in 2016 were invited
      to participate in the study, and 92 students completed the temperament
      questionnaire, for a response rate of 87.5%. Those students' clinical activity
      during their third year was measured by production points and percentage of
      broken appointments extracted from the electronic health record. The results
      showed that the majority of the respondents were extroverts rather than
      introverts and that the extroverts had significantly higher production points and
      significantly fewer broken appointments than the introverts. The most common
      personality preferences were sensing and judging. More than two-thirds of the
      respondents represented the Guardian temperament, one of four categories on the
      temperament measure. These findings help highlight the traits that may contribute
      to success in clinical training during dental school and support the notion that
      clinical success may be influenced by certain personality characteristics as well
      as the technical and specialized skills of dentistry.

PMID- 29196332
TI  - Correlations Between Final-Year Dental Students' Performance on Knowledge-Based
      and Clinical Examinations.
AB  - Dental students are assessed using a range of methods in their final-year
      examinations. The aim of this study was to explore the correlations and
      predictive value of final-year dental students' performance on knowledge-based
      and clinical assessments. Examination data related to applied dental knowledge
      (ADK), exit case presentation (CP), and integrated structured clinical
      examination (ISCE) assessments for five consecutive cohorts of final-year
      students at one U.K. dental school from 2011-12 to 2015-16 were collated. The
      relationships between the scores produced by each assessment were investigated to
      explore the relative contributions of each to the understanding of students'
      abilities across the domains. The study utilized data from all 304 students: 147
      (48.4%) females and 157 (51.6%) males. Significant positive correlations were
      found between ISCE and ADK performance (r(391)=0.42, p<0.001) as well as between
      ISCE and CP (r(391)=0.44, p<0.001). In addition, both ADK performance and CP
      performance were significant predictors (at p<0.001) of ISCE performance. This
      study provides important information about the relationship between these
      students' performance across knowledge (ADK) and clinical (ISCE and CP) domains
      and highlights their predictive value. Further research is required to establish
      if these findings can be generalized and to explore the correlations between
      performance of dental students before and after graduation.

PMID- 29196333
TI  - Validity of Peer Evaluation for Team-Based Learning in a Dental School in Japan.
AB  - The aim of this study was to determine the validity of peer evaluation for team
      based learning (TBL) classes in dental education in comparison with the term-end
      examination records and TBL class scores. Examination and TBL class records of
      256 third- and fourth-year dental students in six fixed prosthodontics courses
      from 2013 to 2015 in one dental school in Japan were investigated. Results of the
      term-end examination during those courses, individual readiness assurance test
      (IRAT), group readiness assurance test (GRAT), group assignment projects (GAP),
      and peer evaluation of group members in TBL classes were collected. Significant
      positive correlations were found between all combinations of peer evaluation,
      IRAT, and term-end examination. Individual scores also showed a positive
      correlation with group score (total of GRAT and GAP). From the investigation of
      the correlations in the six courses, significant positive correlations between
      peer evaluation and individual score were found in four of the six courses. In
      this study, peer evaluation seemed to be a valid index for learning performance
      in TBL classes. To verify the effectiveness of peer evaluation, all students have
      to realize the significance of scoring the team member's performance. Clear
      criteria and detailed instruction for appropriate evaluation are also required.

PMID- 29196334
TI  - Grading Class I Preparations in Preclinical Dental Education: E4D Compare
      Software vs. the Traditional Standard.
AB  - The aim of this study was to compare the effectiveness of a novel assessment
      software system with the traditional grading protocol used in the University of
      Texas School of Dentistry at Houston operative dentistry preclinical curriculum.
      In the study, conducted in 2016, 98 Class I preparations were evaluated both
      traditionally and digitally by two teams of calibrated preclinical faculty
      members (two evaluators for each team). Scores from each faculty pair were
      averaged for the traditional and the digital grading systems, and the scores for
      the two grading systems were compared. The analysis found no significant
      difference between the two grading systems with respect to isthmus width
      (p=0.073) and remaining marginal ridge (p=0.5841), but there was a significant
      difference with respect to pulpal floor depth assessment (p<0.0001). The data
      suggested that both grading techniques can be used with repeatable confidence for
      two out of three grading criteria: isthmus width and remaining marginal ridge. In
      addition, the software offers a self-assessment tool for students to perfect
      their psychomotor skills while promoting independence and immediate feedback.

PMID- 29196335
TI  - An Instrument to Assess Dental Students' Competence in Shared Decision Making: A
      Pilot Study.
AB  - Evidence suggests that involving patients in health care decisions has a positive
      impact on health care outcomes and patients' perception of quality. However, the
      extent to which dental students are trained in communication and shared decision
      making (SDM) differs, and studies have identified a need for intensified learning
      and assessment of this competence. A need to more clearly define and
      operationalize what it means to be proficient in this area has been identified.
      The aim of this study was to operationalize communicative and relational skills
      in a comprehensive assessment instrument for SDM. Relevant skills in information
      exchange, negotiation, communication, and relationship-building were identified
      through an extensive review of previous research and instruments for assessing
      communication competence. Indicators for assessing these skills were formulated.
      The instrument was submitted to a pilot test in 2016 and evaluated on test
      content, internal structure, and response processes. The Assessment of Shared
      Decision Making (ASDM) instrument consists of 18 items addressing various aspects
      of the construct and three types of skills. Findings suggest that the ASDM
      represents a valid measure of SDM with three major components. The importance of
      developing the ASDM lies both in the summative assessment of students'
      communication with patients and for formative assessment purposes. Once
      identified, the components essential for SDM can be woven into the curriculum and
      shared with students. Thus, the ASDM provides a structure that can meet the need
      for intensified learning and assessment of dental students' competence in
      communication and SDM.

PMID- 29196339
TI  - Intra-abdominal infection combined with intra-abdominal hypertension aggravates
      the intestinal mucosal barrier dysfunction.
AB  - Some patients with intra-abdominal infection (IAI) may develop intra-abdominal
      hypertension (IAH) during treatment. The present study investigated the impact of
      IAI combined with IAH on the intestinal mucosal barrier in a rabbit model. Forty
      eight New Zealand white rabbits were randomly divided into four groups: (i) IAI
      and IAH; (ii) IAI alone; (iii) IAH alone; and (iv) Control group. IAI model:
      cecal ligation and puncture for 48 h; IAH model: raised intra-abdominal pressure
      (IAP) of 20 mmHg for 4 h. Pathological changes in intestinal mucosa were
      confirmed by light and scanning electron microscopy. FITC-conjugated dextran
      (FITC-dextran) by gavage was used to measure intestinal mucosal permeability in
      plasma. Endotoxin, d-Lactate, and diamine oxidase (DAO) in plasma were measured
      to determine intestinal mucosal damage. Malonaldehyde (MDA), superoxide dismutase
      (SOD), and GSH in ileum tissues were measured to evaluate intestinal mucosal
      oxidation and reducing state. Histopathologic scores were significantly higher in
      the IAI and IAH group, followed by IAI alone, IAH alone, and the control group.
      FITC-dextran, d-Lactate, DAO, and endotoxin in plasma and MDA in ileum tissues
      had similar trends. GSH and SOD were significantly lowest the in IAI and IAH
      group. Occludin levels were lowest in the ileums of the IAI and IAH group. All
      differences were statistically significant (P-values <0.001). IAI combined with
      IAH aggravates damage of the intestinal mucosal barrier in a rabbit model. The
      combined effects were significantly more severe compared with a single factor.
      IAI combined with IAH should be prevented and treated effectively.

PMID- 29196338
TI  - Proteomics and metabolomics identify molecular mechanisms of aging potentially
      predisposing for chronic lymphocytic leukemia.
AB  - B cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in
      adults, is still essentially incurable despite the development of novel
      therapeutic strategies. This reflects the incomplete understanding of the
      pathophysiology of this disease. A comprehensive proteome analysis of primary
      human B-CLL cells and B cells from younger as well as elderly healthy donors was
      performed. For comparison, the chronic B cell leukemia cell line JVM-13 was also
      included. A principal component analysis comprising 6,945 proteins separated
      these four groups, placing B cells of aged-matched controls between those of
      young donors and B-CLL patients, while identifying JVM-13 as poorly related
      cells. Mass spectrometric proteomics data have been made fully accessible via
      ProteomeXchange with identifier PXD006570-PXD006572, PXD006576, PXD006578, and
      PXD006589-PXD006591. Remarkably, B cells from aged controls displayed significant
      regulation of proteins related to stress management in mitochondria and ROS
      stress such as DLAT, FIS1, and NDUFAB1, and DNA repair, including RAD9A, MGMT,
      and XPA. ROS levels were indeed found significantly increased in B cells but not
      in T cells or monocytes from aged individuals. These alterations may be relevant
      for tumorigenesis and were observed similarly in B-CLL cells. In B-CLL cells,
      some remarkable unique features like the loss of tumor suppressor molecules PNN
      and JARID2, the stress-related serotonin transporter SLC6A4, and high expression
      of ZNF207, CCDC88A, PIGR and ID3, otherwise associated with stem cell phenotype,
      were determined. Alterations of metabolic enzymes were another outstanding
      feature in comparison to normal B cells, indicating increased beta-oxidation of
      fatty acids and increased consumption of glutamine. Targeted metabolomics assays
      corroborated these results. The present findings identify a potential proteome
      signature for immune senescence in addition to previously unrecognized features
      of B-CLL cells and suggest that aging may be accompanied by cellular
      reprogramming functionally relevant for predisposing B cells to transform to B
      CLL cells.

PMID- 29196340
TI  - Dynamics of gaps, vegetation, and plant species with and without fire.
AB  - PREMISE OF THE STUDY: Areas lacking dominant plants, or gaps, can support high
      diversity and specialist species. Previous chronosequence research in Florida
      rosemary scrub showed indistinct gap area patterns with fire and the dependence
      of certain species on gaps. We hypothesized that fire and gap size would affect
      extinction, colonization, diversity, and vegetation composition. METHODS: In 2011
      12, we revisited gaps first sampled in 2003, recording vascular plant and ground
      lichen occurrence by species, gap area, and burn history. We analyzed gap,
      vegetation, and species dynamics using linear mixed models, with Florida rosemary
      scrub patch as a random factor. KEY RESULTS: Gap areas declined quickly during
      the first 10 yr postfire and then stabilized. Between 2003 and 2011-12, unburned
      gaps usually remained extant or split, whereas burned gaps usually merged.
      Unburned gaps tended to shrink, whereas burned gaps became larger. Species
      richness was positively related to gap area, fire, and their interaction. Over
      time, richness declined in unburned gaps and increased in burned gaps. Local
      extinction and colonization of individual species were related to fire between
      2003 and 2011-12. In burned gaps, ground lichens disappeared, but many herbaceous
      species, including those killed by fire, increased occupancy. Colonization of
      most species was favored by burning, large gaps, or both. CONCLUSIONS: In Florida
      rosemary scrub, fire and increasing gap size increased species richness and many
      individual species occurrences, reduced local extinctions, and increased
      colonizations. Therefore, land management activities that encourage the creation
      and maintenance of large gaps will promote biodiversity in this system.

PMID- 29196341
TI  - Vapor pressure deficit predicts epiphyte abundance across an elevational gradient
      in a tropical montane region.
AB  - PREMISE OF THE STUDY: Tropical Montane Cloud Forests (TMCFs) are important
      ecosystems to study and preserve because of their high biodiversity and critical
      roles in local and regional ecosystem processes. TMCFs may be particularly
      affected by changes in climate because of the narrow bands of microclimate they
      occupy and the vulnerability of TMCF species to projected increases in cloud base
      heights and drought. A comprehensive understanding of the structure and function
      of TMCFs is lacking and difficult to attain because of variation in topography
      within and across TMCF sites. This causes large differences in microclimate and
      forest structure at both large and small scales. METHODS: In this study, we
      estimated the abundance of the entire epiphyte community in the canopy
      (bryophytes, herbaceous vascular plants, woody epiphytes, and canopy dead organic
      matter) in six sites. In each of the sites we installed a complete canopy weather
      station to link epiphyte abundance to a number of microclimatic parameters. KEY
      RESULTS: We found significant differences in epiphyte abundance across the sites;
      epiphyte abundance increased with elevation and leaf wetness, but decreased as
      vapor pressure deficit (VPD) increased. Epiphyte abundance had the strongest
      relationship with VPD; there were differences in VPD that could not be explained
      by elevation alone. CONCLUSIONS: By measuring this proxy of canopy VPD, TMCF
      researchers will better understand differences in microclimate and plant
      community composition across TMCF sites. Incorporating such information in
      comparative studies will allow for more meaningful comparisons across TMCFs and
      will further conservation and management efforts in this ecosystem.

PMID- 29196342
TI  - Edaphic history over seedling characters predicts integration and plasticity of
      integration across geologically variable populations of Arabidopsis thaliana.
AB  - PREMISE OF THE STUDY: Studies on phenotypic plasticity and plasticity of
      integration have uncovered functionally linked modules of aboveground traits and
      seedlings of Arabidopsis thaliana, but we lack details about belowground
      variation in adult plants. Functional modules can be comprised of additional
      suites of traits that respond to environmental variation. We assessed whether
      shoot and root responses to nutrient environments in adult A. thaliana were
      predictable from seedling traits or population-specific geologic soil
      characteristics at the site of origin. METHODS: We compared 17 natural accessions
      from across the native range of A. thaliana using 14-day-old seedlings grown on
      agar or sand and plants grown to maturity across nutrient treatments in sand. We
      measured aboveground size, reproduction, timing traits, root length, and root
      diameter. Edaphic characteristics were obtained from a global-scale dataset and
      related to field data. KEY RESULTS: We detected significant among-population
      variation in root traits of seedlings and adults and in plasticity in aboveground
      and belowground traits of adult plants. Phenotypic integration of roots and
      shoots varied by population and environment. Relative integration was greater in
      roots than in shoots, and integration was predicted by edaphic soil history,
      particularly organic carbon content, whereas seedling traits did not predict
      later ontogenetic stages. CONCLUSIONS: Soil environment of origin has significant
      effects on phenotypic plasticity in response to nutrients, and on phenotypic
      integration of root modules and shoot modules. Root traits varied among
      populations in reproductively mature individuals, indicating potential for
      adaptive and integrated functional responses of root systems in annuals.

PMID- 29196343
TI  - Present and future of ecological and evolutionary research in Mediterranean-type
      ecosystems: Conclusions from the last International Mediterranean Ecosystems
      Conference.

PMID- 29196344
TI  - Differential cardiac hypertrophy and signaling pathways in pressure versus volume
      overload.
AB  - Mechanical overload can be classified into pressure overload and volume overload,
      causing concentric and eccentric cardiac hypertrophy, respectively. Here, we
      aimed to differentiate the load-mediated signaling pathways involved in pressure
      versus volume overload cardiac hypertrophy. Pressure or volume overload was
      imposed on C57BL/6J mice by transverse aortic constriction (TAC) or aortic
      regurgitation (AR), respectively. After surgery (2 wk), left ventricular
      structure and function were evaluated by echocardiographic, hemodynamic, and
      histological analyses. Signaling pathways related to hypertrophy, fibrosis,
      angiogenesis, and apoptosis were studied by histological analysis, RT-PCR, and
      Western blot analysis. Although mean wall stress was similar in both TAC and AR
      mice, systolic wall stress was significantly increased in TAC and diastolic wall
      stress was mainly elevated in AR. TAC or AR induced concentric or eccentric
      compensated hypertrophy, respectively. TAC was associated with more significant
      fibrosis and apoptosis, whereas AR was associated with more significant
      angiogenesis. MAPK kinase family, beta-arrestin-2, Akt, and Ca2+-related
      signaling pathways were markedly activated in TAC but mildly upregulated or
      unchanged in AR. Pressure overload and volume overload induce different
      phenotypic and molecular adaptations in cardiac hypertrophy. Most load-related
      signaling pathways assessed in this study predominate in pressure but not volume
      overload. The stimulus-specific heterogeneity in the signaling pathways requires
      distinct manipulations for further mechanistic and pharmacological studies. NEW &
      NOTEWORTHY Using the transverse aortic constriction mouse model and the newly
      developed aortic regurgitation mouse model, we delineated the prominent
      differences between concentric and eccentric cardiac hypertrophy on
      morphological, functional, and molecular levels. Our findings are important for
      the precise diagnosis and treatment of these two types of cardiac hypertrophy.
      Listen to this article's corresponding podcast at
      http://ajpheart.podbean.com/e/chinese-english-language-podcast-on-differential
      cardiac-remodeling-in-tac-vs-ar/ .

PMID- 29196346
TI  - Twenty-first century healthcare: delivering the promise against the reality.

PMID- 29196345
TI  - Mitoprotection attenuates myocardial vascular impairment in porcine metabolic
      syndrome.
AB  - Metabolic syndrome (MetS) leads to cardiac vascular injury, which may reflect in
      increased retention of endothelial progenitor cells (EPCs). Coronary endothelial
      cell (EC) mitochondria partly regulate vascular function and structure. We
      hypothesized that chronic mitoprotection would preserve EC mitochondria and
      attenuate coronary vascular injury and dysfunction in swine MetS. Pigs were
      studied after 16 wk of diet-induced MetS, MetS treated for the last 4 wk with the
      mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg/kg sc once daily), and
      lean controls ( n = 6 each). Cardiac remodeling and function were assessed in
      vivo by multidetector-computed tomography (CT), and coronary artery and sinus
      blood samples were collected. EC mitochondrial density, apoptosis, oxidative
      stress, endothelial nitric oxide synthase immunoreactivity, myocardial
      microvascular density (three-dimensional microcomputed tomography), and coronary
      endothelial function (organ bath) were assessed ex vivo. The number and
      arteriovenous gradient of CD34+/KDR+ EPCs were calculated by FACS (a negative net
      gradient indicating EPC retention). MetS and MetS + ELAM pigs developed similar
      MetS (obesity, hyperlipidemia, insulin resistance, and hypertension). EC
      mitochondrial density decreased in MetS animals compared with lean animals but
      normalized in MetS + ELAM animals. ELAM also attenuated EC oxidative stress and
      apoptosis and improved subendocardial microvascular density. ELAM-induced
      vasculoprotection was reflected by decreased coronary retention of EPCs. ELAM
      also partly improved endothelial nitric oxide synthase immunoreactivity, coronary
      endothelial function, and vessel maturity, whereas myocardial perfusion was
      unaffected. Chronic mitoprotection improved coronary EC mitochondrial density and
      decreased vascular remodeling and dysfunction. However, additional mitochondria
      independent mechanisms likely contribute to MetS-induced cardiac vascular injury.
      NEW & NOTEWORTHY The present study shows that chronic mitoprotection preserved
      coronary endothelial cell mitochondria and decreased vascular injury,
      subendocardial microvascular loss, coronary retention of endothelial progenitor
      cells, and release of markers of vascular injury. However, myocardial perfusion
      remained blunted, suggesting that additional mitochondria-independent mechanisms
      likely contribute to metabolic syndrome-induced cardiac vascular injury.

PMID- 29196347
TI  - Healthcare worker influenza vaccination and sickness absence - an ecological
      study.
AB  - Although Influenza vaccination is recommended for healthcare workers, vaccination
      rates in UK healthcare workers are only around 50%. We investigated the
      association between NHS sickness absence rates (using data from Health and Social
      Care Information Centre quarterly reports), staff vaccination rates and influenza
      vaccine efficacy (from Public Health England), influenza deaths (from the Office
      of National Statistics) and staff satisfaction (from www.NHSstaffsurveys.com).
      Data from 223 healthcare trusts covered approximately 800,000 staff in each of
      four influenza seasons from 2011; overall staff sickness rate was roughly 4.5%.
      Annual vaccination rates varied between 44% and 54%. Higher NHS trust vaccination
      rates were associated with reduced sickness absence (beta = -0.425 [95% CI -0.658
      to -0.192], p<0.001). Thus, a 10% increase in vaccination rate would be
      associated with a 10% fall in sickness absence rate. Influenza vaccination for
      NHS staff is associated with reduced sickness absence rates.

PMID- 29196348
TI  - The value of the physical examination in clinical practice: an international
      survey.
AB  - A structured online survey was used to establish the views of 2,684 practising
      clinicians of all ages in multiple countries about the value of the physical
      examination in the contemporary practice of internal medicine. 70% felt that
      physical examination was 'almost always valuable' in acute general medical
      referrals. 66% of trainees felt that they were never observed by a consultant
      when undertaking physical examination and 31% that consultants never demonstrated
      their use of the physical examination to them. Auscultation for pulmonary wheezes
      and crackles were the two signs most likely to be rated as frequently used and
      useful, with the character of the jugular venous waveform most likely to be rated
      as -infrequently used and not useful. Physicians in contemporary hospital general
      medical practice continue to value the contribution of the physical examination
      to assessment of outpatients and inpatients, but, in the opinion of trainees,
      teaching and demonstration could be improved.

PMID- 29196349
TI  - Screening for obstructive sleep apnoea using the STOPBANG questionnaire and the
      Epworth sleepiness score in patients admitted on the unselected acute medical
      take in a UK hospital.
AB  - Obstructive sleep apnoea (OSA), which is often overlooked in patients presenting
      to primary and secondary care, is an increasingly common comorbidity. The
      prevalence of OSA has not been studied in the unselected acute medical take. The
      aim of this study was to screen for the prevalence of undiagnosed OSA using the
      STOPBANG Questionnaire and the Epworth sleepiness scale (ESS) score in an
      unselected acute medical take. This was a cross-sectional study in a busy UK
      general hospital. Patient demographics, comorbidities, ESS and STOPBANG scores on
      unselected acute medical takes were reviewed and analysed to assess the
      prevalence of OSA. Of 93 patients screened, more than 50% were obese. The
      STOPBANG score was >=3 in 73%. The ESS was significantly increased (>=11) in 20%.
      On multivariate analysis, ESS continued to remain independently associated with
      the STOPBANG score with a p-value of 0.04. The routine use of the STOPBANG
      questionnaire followed by an ESS score in those with a score of >=3 may focus
      evaluation for undetected OSA in the acute medical care setting.

PMID- 29196350
TI  - Frequency of stepping down antibiotics and nebuliser treatment is lower at
      weekends compared to weekdays: an observational study.
AB  - We hypothesised that delays in providing non-urgent medication step-downs at
      weekends to medical management may be associated with increased length of stay.In
      a novel use of electronic prescribing data, we analysed emergency admissions from
      a busy acute medical hospital over 52 weeks from November 2014 to October 2015.
      The main outcomes of interest were switching from intravenous antibiotics to oral
      antibiotics and stopping nebulised bronchodilators. The rate of switching from
      intravenous to oral antibiotics was lower on Saturdays and Sundays compared with
      weekdays, and the rate of stopping nebulised bronchodilators was similarly lower
      at weekends (p<0.001). Median length of stay was shorter in those whose
      antibiotic treatment was stepped down at weekends compared with weekdays (4 days
      versus 5 days, p<0.001). Reduced medication step-downs at weekends may represent
      a bottleneck in patient flow. Electronic prescribing data are a valuable resource
      for future health services research.

PMID- 29196351
TI  - Barriers and facilitators to HIV testing in people age 50 and above: a systematic
      review.
AB  - Approximately 13% of people living with HIV in the UK are unaware of their
      infection. New diagnoses among people >=50 years is increasing. Unique factors
      may be associated with testing in this group. This systematic review aims to
      identify patient and clinician-related barriers/facilitators to HIV testing in
      people aged >=50 years. A systematic electronic search was conducted. Papers were
      assessed for eligibility and data from eligible studies were extracted.
      Barriers/facilitators were grouped, and the number of times they were reported
      was noted. Because of considerable heterogeneity, a narrative approach has been
      undertaken to synthesise data. In total, 17 studies were included. Main barriers
      to testing were low perceived risk and clinicians' preconceptions about older
      people. Main facilitators were regular use of healthcare services or being
      offered/encouraged to test by a healthcare provider. Although being encouraged to
      test was a common facilitator, clinicians' preconceptions about older people was
      the biggest barrier. This shows a divide between clinicians' preconceptions and
      patients' expectations, which may impact on testing rates. This review is an
      important first step in identifying potential barriers/facilitators for further
      study or to be addressed in the design of future interventions.

PMID- 29196353
TI  - The lung microbiome in health and disease.
AB  - The Human Microbiome Project began 10 years ago, leading to a significant growth
      in understanding of the role the human microbiome plays in health and disease. In
      this article, we explain with an emphasis on the lung, the origins of microbiome
      research. We discuss how 16S rRNA gene sequencing became the first major
      molecular tool to examine the bacterial communities present within the human
      body. We highlight the pitfalls of molecular-based studies, such as false
      findings resulting from contamination, and the limitations of 16S rRNA gene
      sequencing. Knowledge about the lung microbiome has evolved from initial
      scepticism to the realisation that it might have a significant influence on many
      illnesses. We also discuss the lung microbiome in the context of disease by
      giving examples of important respiratory conditions. In addition, we draw
      attention to the challenges for metagenomic studies of respiratory samples and
      the importance of systematic bacterial isolation to enable host-microbiome
      interactions to be understood. We conclude by discussing how knowledge of the
      lung microbiome impacts current clinical diagnostics.

PMID- 29196352
TI  - Hearing-impaired young people - a physician's guide .
AB  - Physicians reading this will have a broad range of in-depth knowledge about their
      own subspecialty. However, in daily medical practice there are topics of which
      all physicians should have some knowledge. Those who deal with young people
      should have some knowledge of the needs of the hearing-impaired population within
      this group of patients. This article is intended to provide an overview of young
      people with hearing impairment (HIYP), the challenges they face and what we can
      do to help them. In this paper, we assume that data published regarding hearing
      impaired children apply to HIYP from 13 years (the age at which the transition
      process begins) to 25 years of age (the age at which 'youth' according to the
      World health Organization and the Education Health Care Plan ends).

PMID- 29196355
TI  - Harveian Oration 2017: Triumphs and challenges in a world shaped by medicine.

PMID- 29196354
TI  - Multiple sclerosis, a treatable disease .
AB  - This article reviews our current understanding and modern treatment of multiple
      sclerosis (MS). MS is a disabling condition resulting in devastating social and
      economic impacts. As MS can affect any part of the central nervous system, the
      presentation is often diverse; however, there are key features that can be useful
      in the clinic. We comment on the diagnostic criteria and review the main subtypes
      of MS, including clinically isolated syndrome, relapsing remitting MS, secondary
      progressive MS and primary progressive MS. Although the underlying aetiology of
      MS is still not known, we summarise those with most evidence of association.
      Finally, we aim to present treatment strategies for managing the acute relapse,
      disease-modifying therapies and MS symptoms. This review highlights that
      progressive MS is an area where there is currently a paucity of available disease
      modifying treatments and this will be a major focus for future development.

PMID- 29196356
TI  - The rise of the genome and personalised medicine.
AB  - Virtually all medical specialties are impacted by genetic disease. Enhanced
      understanding of the role of genetics in human disease, coupled with rapid
      advancement in sequencing technology, is transforming the speed of diagnosis for
      patients and providing increasing opportunities to tailor management. As set out
      in the Annual report of the Chief Medical Officer 2016: Generation Genome1 and
      the recent NHS England board paper Creating a genomic medicine service to lay the
      foundations to deliver personalised interventions and treatments,2 the increasing
      'mainstreaming' of genetic testing into routine practice and plans to embed whole
      genome sequencing in the NHS mean that the profile and importance of genomics is
      on the rise for many clinicians. This article provides a brief overview of
      genomics and its current clinical applications, including its contribution to
      personalised medicine. Physicians will be signposted to key issues that will
      allow the successful implementation of genomics for rare disease diagnosis and
      cancer management.

PMID- 29196357
TI  - An approach to familial lymphoedema.
AB  - Lymphoedema is the build-up of lymphatic fluid leading to swelling in the
      tissues. Most commonly it affects the peripheries. Diagnosis is based on clinical
      assessment and imaging with lymphoscintigraphy. Treatment is supportive with
      compression garments, massage, good skin hygiene and prompt use of antibiotics to
      avoid the complication of cellulitis. Most commonly, lymphoedema occurs as a
      result of damage to the lymphatic system following surgery, trauma, radiation or
      infection. However, it can be primary, often associated with a genetic defect
      that causes disruption to the development of the lymphatic system. Common genetic
      conditions associated with lymphoedema include Turner syndrome and Noonan
      syndrome; however, there are numerous others that can be classified based on
      their clinical presentation and associated features. Herein we discuss how to
      diagnose and classify the known primary lymphoedema conditions and how best to
      investigate and manage this group of patients.

PMID- 29196358
TI  - A clinical approach to developmental delay and intellectual disability.
AB  - Global developmental delay and intellectual disability are phenotypically and
      genetically heterogeneous and a specific diagnosis is not reached in many cases.
      This paper outlines a systematic approach to global developmental delay and
      intellectual disability.

PMID- 29196359
TI  - Inherited skin tumour syndromes.
AB  - This article provides an overview of selected genetic skin conditions where
      multiple inherited cutaneous tumours are a central feature. Skin tumours that
      arise from skin structures such as hair, sweat glands and sebaceous glands are
      called skin appendage tumours. These tumours are uncommon, but can have important
      implications for patient care. Certain appendageal tumours, particularly when
      multiple lesions are seen, may indicate an underlying genetic condition. These
      tumours may not display clinical features that allow a secure diagnosis to be
      made, necessitating biopsy and dermatopathological assessment. Coupled with
      robust clinical assessment, biopsy findings can guide genetic testing as,
      increasingly, the causative genes are known for these conditions. Here we review
      illustrative examples of appendageal tumours and relevant advances made in
      genetic discovery, and suggest when referral to a geneticist may need to be
      considered.

PMID- 29196361
TI  - CME Genetic medicine (113042) self-assessment questionnaire.

PMID- 29196360
TI  - The use of panel testing in familial breast and ovarian cancer.
AB  - Advances in sequencing technology have led to the introduction of panel testing
      in hereditary breast and ovarian cancer. While direct-to-consumer testing
      services have become widely available, the clinical validity of many of the genes
      on panel tests remains contentious and risk management guidelines are often
      lacking. This article gives an overview of advantages with panel testing as well
      as important challenges, including clinical translation of test results.

PMID- 29196363
TI  - Lesson of the month 1: Obesity hypoventilation (Pickwickian) syndrome: a
      reversible cause of severe pulmonary hypertension.
AB  - Obesity hypoventilation syndrome (OHS) is a condition in which an individual with
      a body mass index >30 kg/m2 develops daytime alveolar hypoventilation (defined as
      a resting PaCO2 >45 mmHg) that cannot be attributed to other pathologies. It is a
      condition with increasing prevalence and rising cost to healthcare systems
      worldwide. Right heart failure and pulmonary hypertension are well-known
      complications of this syndrome. Here, we present the case of a female patient
      with OHS who presented to our centre with severe pulmonary hypertension, which
      resolved with appropriate treatment. We also review this clinical condition and
      its diagnosis and management.

PMID- 29196362
TI  - A 68-year-old with cranial nerve neuropathies and a troponin rise.
AB  - In this case study, we summarise the inpatient investigations and management of a
      68-year-old woman with Takotsubo cardiomyopathy secondary to a Varicella zoster
      encephalitis and the difficulties inherent with making this diagnosis. She
      presented with evolving cranial nerve neuropathies, which started with a vagal
      nerve mononeuritis and eventually included left-sided sensorineural hearing loss
      and a facial nerve palsy. These symptoms were concomitant with a variety of
      cardiac abnormalities, including fast atrial fibrillation and
      electrocardiographic changes. We summarise some of the current understanding of
      Takotsubo cardiomyopathy and the criteria for its diagnosis. Although left
      ventricular apical ballooning has been described in association with severe
      infections and states of high stress, we have not seen it reported in association
      with a Varicella zoster encephalitis.

PMID- 29196365
TI  - Image of the month: Dysphasia due to injury of the corticobulbar tract following
      traumatic brain injury.

PMID- 29196364
TI  - Lesson of the month 2: Use of thrombolysis for ischaemic stroke in pregnancy - a
      case report and review of literature.
AB  - A nine-week pregnant 33-year-old female presented with sudden-onset right-sided
      hemiparesis, hemisensory loss, dysarthria and homonymous hemianopia. She was
      known to have eleven previous miscarriages and used recreational drugs. A CT-head
      was unremarkable. The patient was subsequently diagnosed with an acute
      thromboembolic infarct and chose alteplase after counselling. During thrombolysis
      an ultrasound identified a foetus with no concerning features.  A post
      thrombolysis CT revealed a left-sided posterior cerebral infarct. CT-venography,
      carotid Doppler, 72-hour Holter monitor, thrombophilia and an autoimmune screen
      were all normal. A transthoracic echocardiogram demonstrated a mobile intra
      atrial septum with a patent foramen ovale confirmed on bubble echocardiogram.
      Three days post-thrombolysis the patient requested a termination of pregnancy. A
      subsequent transvaginal ultrasound demonstrated a missed miscarriage for which
      the patient underwent evacuation of retained products of conception.
      Multidisciplinary care ensured that her sensorimotor deficit resolved grossly
      with only mild dysarthria and right-hand fine motor incoordination.

PMID- 29196366
TI  - The application game.

PMID- 29196367
TI  - 'T3 or not T3?': A poetic guide to the thyroid exam.

PMID- 29196368
TI  - Referring wisely? or referring when you need help?

PMID- 29196369
TI  - Response.

PMID- 29196370
TI  - Medical problems in pregnancy.

PMID- 29196371
TI  - Medical problems in pregnancy.

PMID- 29196372
TI  - Acute geriatrics at the front door.

PMID- 29196373
TI  - The emergence of sarcopenia as an important entity in older people.

PMID- 29196374
TI  - Sarcopenia, frailty and exercise.

PMID- 29196375
TI  - Antisynthetase syndrome.

PMID- 29196376
TI  - The hyperacute neurology team.

PMID- 29196377
TI  - The hyperacute neurology team.

PMID- 29196378
TI  - Response.

PMID- 29196379
TI  - Short-term Repeat Magnetic Resonance Imaging Scans in Suspected Early Axial
      Spondyloarthritis Are Clinically Relevant Only in HLA-B27-positive Male Subjects.
AB  - OBJECTIVE: Our study investigated the natural history of magnetic resonance
      imaging (MRI)-determined bone marrow edema over a 12-week period in individuals
      with suspected axial spondyloarthritis. METHODS: There were 109 MRI scans
      performed on 30 patients who fulfilled the Assessment of Spondyloarthritis
      international Society inflammatory back pain criteria at baseline and at 4, 8,
      and 12 weeks. RESULTS: There were 29 patients who completed the study. Only 4
      (14%) patients changed from MRI-negative to MRI-positive (all HLA-B27-positive,
      OR 2.74). Three of 7 (43%) male HLA-B27-positive patients, 1 of 8 (12.5%) HLA-B27
      positive female patients, and no HLA-B27-negative patients changed from MRI-
      negative to -positive. CONCLUSION: Repeat MRI scans within a 12-week period
      should be considered in HLA-B27-positive males.

PMID- 29196380
TI  - Disease Activity of Juvenile Idiopathic Arthritis during and after Pregnancy: A
      Prospective Multicenter Study.
AB  - OBJECTIVE: To study disease activity in women with juvenile idiopathic arthritis
      (JIA) during and after pregnancy. There is little previous knowledge about this
      topic. METHODS: Our study included 135 pregnancies in 114 women with JIA. Disease
      activity was assessed at 7 timepoints before, throughout, and after pregnancy
      with the Disease Activity Score-28-C-reactive protein 3 (DAS28-CRP3). Scores
      assessed at each visit were analyzed in a linear mixed model. The same
      statistical method was used to study self-reported physical function, pain, and
      mental health. RESULTS: Almost 80% of the women were in remission or had low
      disease activity during and after pregnancy. Although disease activity was stable
      throughout the study period, we found that DAS28 6 weeks postpartum increased
      significantly compared to the first trimester (2.78 vs 2.51, p = 0.005) and third
      trimester (2.78 vs 2.56, p = 0.011), respectively. DAS28 decreased significantly
      between 6 weeks and 12 months postpartum (2.78 vs 2.54, p = 0.014). Self-reported
      mental health was significantly better 6 weeks postpartum than before pregnancy
      (Medical Outcomes Study Short Form-36 Mental Health subscale 80.7 vs 76.5, p =
      0.039). Self-reported pain was stable. Physical function was significantly worse
      in the third trimester of pregnancy than postpartum (Modified Health Assessment
      Questionnaire 0.57 vs 0.39, p < 0.001). CONCLUSION: In women with JIA, disease
      activity was highest 6 weeks postpartum, but altogether low and stable in the
      period from planning pregnancy to 1 year after delivery.

PMID- 29196381
TI  - Sharing Ongoing Care with Primary Care Physicians Opens Up Opportunity for
      Timelier and Earlier Care by Rheumatologists for Patients with New Inflammatory
      Polyarthritis.
AB  - OBJECTIVE: In our region in Quebec, Canada, access to rheumatologists is very
      limited. Sharing followup of stable patients with their primary care physicians
      (PCP) could increase access to rheumatologists. In our study, we assessed the
      feasibility and potential benefits of sharing followup of inflammatory arthritis
      (IA) patients with their PCP. METHODS: We reviewed the clinical records of 300
      patients with peripheral arthritis who presented at our rheumatology outpatient
      clinic between July and October 2015. We distributed questionnaires to their
      treating rheumatologist, asking whether a PCP could participate in the followup
      of the patient and whether there were any factors that would prevent shared
      followup. We also distributed questionnaires to PCP to assess their level of
      comfort in participating in the followup care of patients with arthritis.
      RESULTS: Chart review was completed on 300 patients. There was no treatment
      modification in 49% of the cases, and 38% of the visits were deemed unnecessary
      by the attending rheumatologist. We found that 74% of PCP were very interested in
      sharing the arthritis followup care of their patients. According to PCP, the main
      barriers to shared followup were treatment with biological agents, active
      disease, and need for infiltrations. Main organizational barriers were the lack
      of rheumatologist availability to see patients urgently (46%) and the lack of
      clear guidelines for the management of IA (58%). CONCLUSION: Up to 38% of
      peripheral IA visits to a rheumatologist could have been prevented and done by a
      PCP. In our department, this represented up to 19 followup visits per week that
      could have been avoided by involving a PCP.

PMID- 29196382
TI  - Relatedness of Antibodies to Peptides Containing Homocitrulline or Citrulline in
      Patients with Rheumatoid Arthritis.
AB  - OBJECTIVE: Antibodies that target citrullinated protein/peptide (ACPA) and
      homocitrullinated/carbamylated protein/peptide (AHCPA) are associated with
      rheumatoid arthritis (RA). The relationship between ACPA and AHCPA remains
      unclear. We examined the expression and cross-reactivity of these antibodies
      using citrulline- and homocitrulline-containing synthetic peptides, CitJED and
      HomoCitJED, respectively, which have equal numbers of citrulline or
      homocitrulline residues on the same peptide backbone. METHODS: Serum from healthy
      subjects (n = 51) and patients with RA (n = 137), systemic lupus erythematosus
      (SLE; n = 37), and psoriatic arthritis (PsA; n = 37) were screened for IgG anti
      CitJED and anti-HomoCitJED antibodies by ELISA. Cross-reactivity of these
      antibodies was examined by inhibition with various concentrations of CitJED and
      HomoCitJED. RESULTS: Out of 137 patients with RA, antibodies to CitJED and
      HomoCitJED were detected in 69 (50%) and 78 (57%), respectively. Anti-CitJED and
      HomoCitJED antibodies were 77% concordant and their levels were strongly
      correlated [Spearman correlation coefficient (rs) = 0.6676]. Sera from 25/27
      patients (93%) with RA were inhibited by both CitJED and HomoCitJED with equal or
      higher affinity for the cognate (homologous) peptide. CONCLUSION: Antibodies to
      CitJED and HomoCitJED frequently occurred in RA, but were not found in SLE or
      PsA, suggesting that these antibodies are specific to RA. Cross-reactivity
      between anti-HomoCitJED and anti-CitJED antibodies suggests that ACPA and AHCPA
      are derived from the same B cell population and both may contribute to the
      pathogenesis of RA.

PMID- 29196384
TI  - Trends in Joint Replacement Surgery in Patients with Rheumatoid Arthritis.
AB  - OBJECTIVE: This study analyzed trends in large total joint arthroplasties (TJA)
      and in the proportion of these procedures performed on patients with rheumatoid
      arthritis (RA). METHODS: The US Nationwide Inpatient Sample (2002-2012) was used
      to identify the incidences of total shoulder (TSA), elbow (TEA), knee (TKA), hip
      (THA), and ankle (TAA) arthroplasty and the proportion of these performed with
      coexisting RA. RESULTS: The prevalence of RA among patients with TJA increased
      3.0%. The prevalence of RA among cases of TEA and TSA decreased by 50% (p <
      0.0001) and 18% (p = 0.0016), respectively; a 38.0% decrease occurred in the
      prevalence of RA among TAA (p = 0.06); and nonsignificant increases were seen
      among THA and TKA. The average age difference between RA and non-RA patients
      undergoing TJA narrowed by 2 years (p < 0.0001). There was a greater reduction in
      the proportion of TSA, TEA, and TAA groups among women with RA than men with RA.
      In the TSA and TEA groups, there was a reduction in the proportion of whites with
      RA, but not blacks. The proportion of privately insured TSA and TAA patients with
      RA decreased, while patients with RA undergoing TSA, TEA, or TAA who were
      receiving Medicaid (government medical insurance) remained relatively stable over
      time. CONCLUSION: The prevalence of RA has decreased among TSA and TEA patients.
      A nonsignificant decline occurred among TAA patients. The average age of TJA
      patients with RA is beginning to mirror those without RA. Sex ratios for TSA,
      TEA, and TAA patients are following a similar pattern. These results may be
      evidence of the success of modern RA treatment strategies.

PMID- 29196383
TI  - Opioid Analgesic Use in Patients with Ankylosing Spondylitis: An Analysis of the
      Prospective Study of Outcomes in an Ankylosing Spondylitis Cohort.
AB  - OBJECTIVE: Opioid analgesics may be prescribed to ankylosing spondylitis (AS)
      patients with pain that is unresponsive to antirheumatic treatment. Our study
      assessed factors associated with opioid usage in AS. METHODS: A prospective
      cohort of 706 patients with AS meeting modified New York criteria followed at
      least 2 years underwent comprehensive clinical evaluation of disease activity and
      functional impairment. These were assessed by the Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index
      (BASFI). Radiographic severity was assessed by the Bath Ankylosing Spondylitis
      Radiology Index and modified Stokes Ankylosing Spondylitis Scoring System.
      Medications taken concurrently with opioids, as well as C-reactive protein (CRP)
      levels and erythrocyte sedimentation rate (ESR), were determined at each study
      visit, performed every 6 months. Analyses were carried out at baseline, and
      longitudinal multivariable models were developed to identify factors
      independently associated with chronic and intermittent opioid usage over time.
      RESULTS: Factors significantly associated with opioid usage, especially chronic
      opioid use, included longer disease duration, smoking, lack of exercise, higher
      disease activity (BASDAI) and functional impairment (BASFI), depression,
      radiographic severity, and cardiovascular disease. Patients taking opioids were
      more likely to be using anxiolytic, hypnotic, antidepressant, and muscle relaxant
      medications. Multivariable analysis underscored the association with smoking,
      older age, antitumor necrosis factor agent use, and psychoactive drugs, as well
      as with subjective but not objective determinants of disease activity.
      CONCLUSION: Opioid usage was more likely to be associated with subjective
      measures (depression, BASDAI, BASFI) than objective measures (CRP, ESR),
      suggesting that pain in AS may derive from sources other than spinal inflammation
      alone.

PMID- 29196385
TI  - Characteristic and Outcome of Psoriatic Arthritis Patients with Hyperuricemia.
AB  - OBJECTIVE: To determine the characteristics of patients with psoriatic arthritis
      (PsA) who have hyperuricemia (HUC) and their outcomes, especially cardiovascular
      (CVD) and kidney diseases. METHODS: Patients have been followed prospectively at
      the PsA clinic according to a standard protocol at 6- to 12-month intervals. We
      defined HUC in men > 450 umol/l or women > 360 umol/l. We matched patients with
      HUC based on sex and age +/- 5 years with normal uric acid patients. Demographics
      information and disease characteristics were reviewed. Outcomes of patients with
      HUC, especially CVD and kidney diseases, were recorded. Conditional logistic
      regression was performed to determine factors independently associated with HUC
      in patients with PsA. RESULTS: There were 325 (31.9%) out of 1019 patients with
      PsA who had HUC. Of these, 318 cases were matched to 318 controls. There were 11
      (3.4%) out of 325 patients with HUC who had gout. Patients with HUC had longer
      disease duration and a higher Psoriasis Area and Severity Index. They had more
      concurrent comorbidities, including CVD and metabolic diseases, as well as higher
      prevalence of kidney stones and higher creatinine. Only 1 patient with HUC was
      treated with allopurinol at first evaluation visit and 7 patients during
      followup. Over the followup, 163 of the 318 patients had persistent HUC (pHUC)
      for more than 2 visits. Patients with pHUC developed more myocardial infarction,
      heart failure, and renal impairment. Multivariate analysis showed an association
      between pHUC, PsA disease duration, and obesity. CONCLUSION: HUC is common in
      patients with PsA, especially in those with longer disease duration and obesity.
      Proper control of HUC and metabolic diseases may play a preventive role in
      improving PsA outcomes.

PMID- 29196388
TI  - Outcome and recovery in first-episode psychosis.
AB  - There is now a good body of evidence about factors that determine outcome and
      recovery in a first episode of psychosis. However, so far, this is of limited
      benefit when making predictions at an individual level. Treatment protocols are
      one size fits all and the recommended duration of medication remains unclear.
      What is needed is a more sophisticated approach to predicting outcomes and
      tailoring treatment options to the individual. Removing predisposing factors is
      an important aspect of this.

PMID- 29196389
TI  - Idles: 'Stendhal Syndrome' - psychiatry in music.

PMID- 29196390
TI  - Network meta-analysis: drawing conclusions regarding trials of psychosocial
      interventions for bipolar disorder.
AB  - Network meta-analysis (NMA) is a statistical technique for making direct and
      indirect comparisons between different treatment and control groups. Despite its
      many advantages, NMA may be misleading when evaluating networks that are
      disconnected, inconsistent or of low reliability and validity. We review how well
      the analysis of trials of adjunctive psychosocial treatment in bipolar disorder
      is served by NMA. We conclude with recommendations for future treatment trials in
      bipolar disorder and guidelines for NMAs.

PMID- 29196392
TI  - T2 Trainspotting: addiction in a digital age - psychiatry in the movies.

PMID- 29196391
TI  - Prison mental health in-reach teams in England: the care programme approach and
      sexual abuse/violence.
AB  - Prison mental health in-reach teams have doubled in size over the past decade and
      case-loads have reduced. Since 2010 it has been mandatory for keyworkers to ask
      whether prisoners with serious mental illness being treated under the care
      programme approach have experienced sexual or physical abuse. This is known as
      routine enquiry and should take place for these prisoners but NHS England, the
      commissioners, do not audit this activity. It is time to review current
      interventions and their associated outcomes.

PMID- 29196393
TI  - Kathleen Jones' Asylums and After. A Revised History of the Mental Health
      Services: From the Early 18th Century to the 1990s (1993) - reflection.

PMID- 29196394
TI  - Punk rock made me a psycho-therapissed - psychiatry in music.

PMID- 29196395
TI  - The evidence for lithium in suicide prevention.

PMID- 29196396
TI  - Authors' reply.

PMID- 29196397
TI  - Where is the argument for the conceptual slippery slope?

PMID- 29196398
TI  - Author's reply.

PMID- 29196399
TI  - Authors' reply.

PMID- 29196400
TI  - The Pool judgment has not changed the law of expert evidence.

PMID- 29196401
TI  - Authors' reply.

PMID- 29196402
TI  - Conflating sexual orientation and gender identity.

PMID- 29196403
TI  - Authors' reply.

PMID- 29196405
TI  - The medical profession and stigma against people who use drugs.

PMID- 29196404
TI  - Authors' reply.

PMID- 29196406
TI  - Authors' reply.

PMID- 29196407
TI  - Corrections.

PMID- 29196408
TI  - Kaleidoscope.

PMID- 29196409
TI  - The Psychiatry Ashes: I can't believe it's not cricket!

PMID- 29196411
TI  - Expression of TP53 is associated with the outcome of MCL independent of MIPI and
      Ki-67 in trials of the European MCL Network.
AB  - Currently, prediction of time to treatment failure (TTF) and overall survival
      (OS) in mantle cell lymphoma (MCL) is based on the clinical factors included in
      the Mantle Cell Lymphoma International Prognostic Index (MIPI), and proliferation
      is assessed by Ki67. However, TP53 and SOX11 immunohistochemistry might improve
      risk stratification. We performed SOX11 and TP53 immunohistochemistry on the so
      far largest published cohort of lymphoma specimens (n = 365). All patients were
      treated in prospective trials of the European MCL Network. In multivariate
      analyses, including MIPI and Ki67, SOX11 expression was not associated with TTF,
      but patients with low SOX11 expression had shorter OS. On the contrary, high TP53
      expression was a strong predictor of TTF and inferior OS compared with low TP53
      expression in univariate and multivariate analyses adjusting for MIPI score and
      Ki-67 index (hazard ratio [HR], 2.0; P = .0054 for TTF, and HR, 2.1; P = .068 for
      OS). In particular, patients with high TP53 expression (>50% positive lymphoma
      cells) had a shorter TTF and poor OS independent of both MIPI score and Ki-67
      index. Thus, TP53 immunohistochemistry is a suitable test for routine diagnostic
      practice to assess MCL prognosis.

PMID- 29196412
TI  - A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33
      positive acute myeloid leukemia.
AB  - Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting
      of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33,
      which is expressed in the majority of acute myeloid leukemia (AML) patients. This
      phase 1 study evaluated the safety, pharmacokinetics, and preliminary activity of
      vadastuximab talirine and determined the recommended monotherapy dose in patients
      with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab
      talirine in specific subpopulations of relapsed AML, and in a cohort of older,
      treatment-naive patients. Patients received vadastuximab talirine IV on day 1 (5
      60 ug/kg) or on days 1 and 4 (20 ug/kg) of 21-day cycles. A total of 131 patients
      (median age, 73 years [range, 26-89 years]) had intermediate I-II (48%) or
      adverse (34%) risk by European LeukemiaNet classification; 50% of patients had
      underlying myelodysplasia. Two dose-limiting toxicities (grade 2 pulmonary
      embolism and grade 4 hypocellular marrow) occurred during dose finding. Most
      adverse events (AEs) were consistent with myelosuppression; nonhematologic AEs
      included fatigue, nausea, and diarrhea. The 30-day mortality was 8%. At the
      recommended monotherapy dose of 40 ug/kg, the complete remission + CRi rate was
      28% (5 of 18 patients); 50% of patients who responded achieved minimal residual
      disease negativity. In patients across dose levels who achieved CR or CRi, the
      median time to full count recovery was 6.4 weeks for neutrophils (>=1000/uL) and
      10.6 weeks for platelets (>=100 * 109/L). Vadastuximab talirine demonstrates
      activity and a tolerable safety profile as a single agent in patients with AML.
      The recommended monotherapy dose of vadastuximab talirine is 40 ug/kg. This trial
      was registered at www.clinicaltrials.gov as # NCT01902329.

PMID- 29196413
TI  - The fungal snoRNAome.
AB  - Small nucleolar RNAs (snoRNAs) are essential players in the rRNA biogenesis due
      to their involvement in the nucleolytic processing of the precursor and the
      subsequent guidance of nucleoside modifications. Within the kingdom Fungi, merely
      a few species-specific surveys have explored their snoRNA repertoire. However,
      the wide range of the snoRNA landscape spanning all major fungal lineages has not
      been mapped so far, mainly because of missing tools for automatized snoRNA
      detection and functional analysis. For the first time, we report here a
      comprehensive inventory of fungal snoRNAs together with a functional analysis and
      an in-depth investigation of their evolutionary history including innovations,
      deletions, and target switches. This large-scale analysis, incorporating more
      than 120 snoRNA families with more than 7700 individual snoRNA sequences,
      catalogs and clarifies the landscape of fungal snoRNA families, assigns functions
      to previously orphan snoRNAs, and increases the number of sequences by 450%. We
      also show that the snoRNAome is subject to ongoing rearrangements and
      adaptations, e.g., through lineage-specific targets and redundant guiding
      functions.

PMID- 29196416
TI  - Correction: miR-103/107 Promote Metastasis of Colorectal Cancer by Targeting the
      Metastasis Suppressors DAPK and KLF4.

PMID- 29196417
TI  - Correction: Myc Induces miRNA-Mediated Apoptosis in Response to HDAC Inhibition
      in Hematologic Malignancies.

PMID- 29196418
TI  - Correction: CRLX101, a Nanoparticle-Drug Conjugate Containing Camptothecin,
      Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1alpha.

PMID- 29196415
TI  - Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers.
AB  - Bacteria may play a role in esophageal adenocarcinoma (EAC) and esophageal
      squamous cell carcinoma (ESCC), although evidence is limited to cross-sectional
      studies. In this study, we examined the relationship of oral microbiota with EAC
      and ESCC risk in a prospective study nested in two cohorts. Oral bacteria were
      assessed using 16S rRNA gene sequencing in prediagnostic mouthwash samples from n
      = 81/160 EAC and n = 25/50 ESCC cases/matched controls. Findings were largely
      consistent across both cohorts. Metagenome content was predicted using PiCRUST.
      We examined associations between centered log-ratio transformed taxon or
      functional pathway abundances and risk using conditional logistic regression
      adjusting for BMI, smoking, and alcohol. We found the periodontal pathogen
      Tannerella forsythia to be associated with higher risk of EAC. Furthermore, we
      found that depletion of the commensal genus Neisseria and the species
      Streptococcus pneumoniae was associated with lower EAC risk. Bacterial
      biosynthesis of carotenoids was also associated with protection against EAC.
      Finally, the abundance of the periodontal pathogen Porphyromonas gingivalis
      trended with higher risk of ESCC. Overall, our findings have potential
      implications for the early detection and prevention of EAC and ESCC. Cancer Res;
      77(23); 6777-87. (c)2017 AACR.

PMID- 29196419
TI  - Recurrent Hemobilia Due to Right Hepatic Artery Pseudoaneurysm.
AB  - Hemobilia is a potentially life-threatening clinical issue, the etiology of which
      iatrogenesis is playing increasingly more prominent role. Nowadays the most
      frequent etiology of hemobilia has shifted toward iatrogenesis owing to
      increasingly more frequent performance of liver procedures, either open or
      minimally invasive. Here we report a rare case of recurrent hemobilia after
      transarterial embolization. A man, aged 57 years, presented with Quincke's triad
      after cholecystectomy. Computed tomography imaging revealed a pseudoaneurysm of
      the right hepatic artery. Transarterial embolization failed, and hemobilia
      recurred. The patient underwent open ligation of the right hepatic artery.
      Transarterial embolization is a definitive treatment of hemobilia due to vascular
      issues. The choice of embolizing agent is crucial in transarterial embolization.

PMID- 29196420
TI  - Fibrillary Glomerulonephritis in Primary Sjogren's Syndrome: A Rare Cause of
      Renal Failure.
AB  - Renal involvement in primary Sjogren's syndrome (pSS) varies in severity and
      prevalence. Although previously felt to be uncommon, kidneys can be involved in
      25% to 30% of pSS patients. Fibrillary glomerulonephritis (FGN) is a rare primary
      glomerular disease that can occur in association with another autoimmune
      condition or malignancy. The diagnosis relies on renal biopsy findings of
      haphazardly arranged fibrils in all glomerular compartments and distinction from
      other forms of fibrillary glomerulopathies such as renal amyloidosis and
      immunotactoid glomerulopathy. FGN responds poorly to immunosuppressive therapy
      and has a poor prognosis. Here, we describe a case of FGN in a patient with
      asymptomatic pSS. We describe the diagnostic work-up, clinical course, treatment
      utilized, and 1-year follow-up. There is one other case in the literature of FGN
      in a patient with pSS. The rarity of this association and distinction of FGN from
      other forms of renal involvement in pSS is important as it impacts therapy and
      prognosis. The case highlights electron microscopy findings in FGN and poor
      prognosis.

PMID- 29196422
TI  - Adversity-related injury in adolescence is associated with increased risk of
      suicide, alcohol and drug-related deaths in the decade following admission.

PMID- 29196423
TI  - Delayed parenteral nutrition reduced new infections in critically ill children.

PMID- 29196424
TI  - Within and beyond Biology Education Research: Steps toward Cross-Disciplinary
      Collaboration.

PMID- 29196421
TI  - Integrative model of coronary flow in anatomically based vasculature under
      myogenic, shear, and metabolic regulation.
AB  - Coronary blood flow is regulated to match the oxygen demand of myocytes in the
      heart wall. Flow regulation is essential to meet the wide range of cardiac
      workload. The blood flows through a complex coronary vasculature of elastic
      vessels having nonlinear wall properties, under transmural heterogeneous
      myocardial extravascular loading. To date, there is no fully integrative flow
      analysis that incorporates global and local passive and flow control
      determinants. Here, we provide an integrative model of coronary flow regulation
      that considers the realistic asymmetric morphology of the coronary network, the
      dynamic myocardial loading on the vessels embedded in it, and the combined
      effects of local myogenic effect, local shear regulation, and conducted metabolic
      control driven by venous O2 saturation level. The model predicts autoregulation
      (approximately constant flow over a wide range of coronary perfusion pressures),
      reduced heterogeneity of regulated flow, and presence of flow reserve, in
      agreement with experimental observations. Furthermore, the model shows that the
      metabolic and myogenic regulations play a primary role, whereas shear has a
      secondary one. Regulation was found to have a significant effect on the flow
      except under extreme (high and low) inlet pressures and metabolic demand. Novel
      outcomes of the model are that cyclic myocardial loading on coronary vessels
      enhances the coronary flow reserve except under low inlet perfusion pressure,
      increases the pressure range of effective autoregulation, and reduces the network
      flow in the absence of metabolic regulation. Collectively, these findings
      demonstrate the utility of the present biophysical model, which can be used to
      unravel the underlying mechanisms of coronary physiopathology.

PMID- 29196426
TI  - A Model for Postdoctoral Education That Promotes Minority and Majority Success in
      the Biomedical Sciences.
AB  - How does the United States maintain the highest-quality research and teaching in
      its professional science workforce and ensure that those in this workforce are
      effectively trained and representative of national demographics? In the pathway
      to science careers, the postdoctoral stage is formative, providing the
      experiences that define the independent work of one's first faculty position. It
      is also a stage in which underrepresented minorities (URMs) disproportionately
      lose interest in pursuing academic careers in science and, models suggest, a
      point at which interventions to increase proportions of URMs in such careers
      could be most effective. We present a mixed-methods, case study analysis from 17
      years of the Fellowships in Research and Science Teaching (FIRST) postdoctoral
      program, to our knowledge the largest and longest continuously running science
      postdoctoral program in the United States. We demonstrate that FIRST fellows, in
      sharp contrast to postdocs overall, are inclusive of URMs (50% African American;
      70% women) and as or more successful in their fellowships and beyond as a
      comparison group (measured by publication rate, attainment of employment in
      academic science careers, and eventual research grant support). Analysis of
      alumni surveys and focus group discussions reveals that FIRST fellows place
      highest value on the cohort-driven community and the developmental teaching and
      research training the program provides.

PMID- 29196425
TI  - Providing Social Support for Underrepresented Racial and Ethnic Minority PhD
      Students in the Biomedical Sciences: A Career Coaching Model.
AB  - Improvement in the proportion of underrepresented racial and ethnic minorities
      (URMs) in academic positions has been unsatisfactory. Although this is a complex
      problem, one key issue is that graduate students often rely on research mentors
      for career-related support, the effectiveness of which can be variable. We
      present results from a novel academic career "coaching" intervention, one aim of
      which was to provide supplementary social support for PhD students, particularly
      those from underrepresented backgrounds. Coaching was delivered both within small
      groups and on an individual basis, with a diverse group of coaches and students
      coming from many universities. Coaches were provided with additional diversity
      training. Ninety-six semistructured interviews with 33 URM students over 3 years
      were analyzed using a qualitative framework approach. For most of the URM PhD
      students, coaching provided social support in the form of emotional,
      informational, and appraisal support. Coaching groups provided a noncompetitive
      environment and "community of support" within which students were able to learn
      from one another's experiences and discuss negative and stressful experiences
      related to their graduate school, lab, or career plans. This coached peer group
      model is capable of providing the social support that many URM students do not
      find at their home universities.

PMID- 29196427
TI  - Development of a Biological Science Quantitative Reasoning Exam (BioSQuaRE).
AB  - Multiple reports highlight the increasingly quantitative nature of biological
      research and the need to innovate means to ensure that students acquire
      quantitative skills. We present a tool to support such innovation. The Biological
      Science Quantitative Reasoning Exam (BioSQuaRE) is an assessment instrument
      designed to measure the quantitative skills of undergraduate students within a
      biological context. The instrument was developed by an interdisciplinary team of
      educators and aligns with skills included in national reports such as BIO2010,
      Scientific Foundations for Future Physicians, and Vision and Change Undergraduate
      biology educators also confirmed the importance of items included in the
      instrument. The current version of the BioSQuaRE was developed through an
      iterative process using data from students at 12 postsecondary institutions. A
      psychometric analysis of these data provides multiple lines of evidence for the
      validity of inferences made using the instrument. Our results suggest that the
      BioSQuaRE will prove useful to faculty and departments interested in helping
      students acquire the quantitative competencies they need to successfully pursue
      biology, and useful to biology students by communicating the importance of
      quantitative skills. We invite educators to use the BioSQuaRE at their own
      institutions.

PMID- 29196429
TI  - Engaging Undergraduate Biology Students in Scientific Modeling: Analysis of Group
      Interactions, Sense-Making, and Justification.
AB  - National calls for improving science education (e.g., Vision and Change)
      emphasize the need to learn disciplinary core ideas through scientific practices.
      To address this need, we engaged small groups of students in developing
      diagrammatic models within two (one large-enrollment and one medium-enrollment)
      undergraduate introductory biology courses. During these activities, students
      developed scientific models of biological phenomena such as enhanced growth in
      genetically modified fish. To investigate whether undergraduate students
      productively engaged in scientific practices during these modeling activities, we
      recorded groups of students as they developed models and examined three
      characteristics: how students 1) interacted with one another, 2) made sense of
      phenomena, and 3) justified their ideas. Our analysis indicates that students
      spent most of the time on task, developing and evaluating their models. Moreover,
      they worked cooperatively to make sense of core ideas and justified their ideas
      to one another throughout the activities. These results demonstrate that, when
      provided with the opportunity to develop models during class, students in large
      enrollment lecture courses can productively engage in scientific practices. We
      discuss potential reasons for these outcomes and suggest areas of future research
      to continue advancing knowledge regarding engaging students in scientific
      practices in large-enrollment lecture courses.

PMID- 29196428
TI  - Measurement Instrument for Scientific Teaching (MIST): A Tool to Measure the
      Frequencies of Research-Based Teaching Practices in Undergraduate Science
      Courses.
AB  - The Scientific Teaching (ST) pedagogical framework provides various approaches
      for science instructors to teach in a way that more closely emulates how science
      is practiced by actively and inclusively engaging students in their own learning
      and by making instructional decisions based on student performance data. Fully
      understanding the impact of ST requires having mechanisms to quantify its
      implementation. While many useful instruments exist to document teaching
      practices, these instruments only partially align with the range of practices
      specified by ST, as described in a recently published taxonomy. Here, we describe
      the development, validation, and implementation of the Measurement Instrument for
      Scientific Teaching (MIST), a survey derived from the ST taxonomy and designed to
      gauge the frequencies of ST practices in undergraduate science courses. MIST
      showed acceptable validity and reliability based on results from 7767 students in
      87 courses at nine institutions. We used factor analyses to identify eight
      subcategories of ST practices and used these categories to develop a short
      version of the instrument amenable to joint administration with other research
      instruments. We further discuss how MIST can be used by instructors, departments,
      researchers, and professional development programs to quantify and track changes
      in ST practices.

PMID- 29196431
TI  - Editor's note: shame, stigma and medicine.

PMID- 29196430
TI  - Aligning Practice to Policies: Changing the Culture to Recognize and Reward
      Teaching at Research Universities.
AB  - Recent calls for improvement in undergraduate education within STEM (science,
      technology, engineering, and mathematics) disciplines are hampered by the methods
      used to evaluate teaching effectiveness. Faculty members at research universities
      are commonly assessed and promoted mainly on the basis of research success. To
      improve the quality of undergraduate teaching across all disciplines, not only
      STEM fields, requires creating an environment wherein continuous improvement of
      teaching is valued, assessed, and rewarded at various stages of a faculty
      member's career. This requires consistent application of policies that reflect
      well-established best practices for evaluating teaching at the department,
      college, and university levels. Evidence shows most teaching evaluation practices
      do not reflect stated policies, even when the policies specifically espouse
      teaching as a value. Thus, alignment of practice to policy is a major barrier to
      establishing a culture in which teaching is valued. Situated in the context of
      current national efforts to improve undergraduate STEM education, including the
      Association of American Universities Undergraduate STEM Education Initiative,
      this essay discusses four guiding principles for aligning practice with stated
      priorities in formal policies: 1) enhancing the role of deans and chairs; 2)
      effectively using the hiring process; 3) improving communication; and 4)
      improving the understanding of teaching as a scholarly activity. In addition,
      three specific examples of efforts to improve the practice of evaluating teaching
      are presented as examples: 1) Three Bucket Model of merit review at the
      University of California, Irvine; (2) Evaluation of Teaching Rubric, University
      of Kansas; and (3) Teaching Quality Framework, University of Colorado, Boulder.
      These examples provide flexible criteria to holistically evaluate and improve the
      quality of teaching across the diverse institutions comprising modern higher
      education.

PMID- 29196433
TI  - NHS may have to abandon waiting times targets because of funding shortfall,
      leaders say.

PMID- 29196432
TI  - Shame, stigma and medicine.

PMID- 29196434
TI  - Type III Intermediate Filaments Desmin, Glial Fibrillary Acidic Protein (GFAP),
      Vimentin, and Peripherin.
AB  - SummaryType III intermediate filament (IF) proteins assemble into cytoplasmic
      homopolymeric and heteropolymeric filaments with other type III and some type IV
      IFs. These highly dynamic structures form an integral component of the
      cytoskeleton of muscle, brain, and mesenchymal cells. Here, we review the current
      ideas on the role of type III IFs in health and disease. It turns out that they
      not only offer resilience to mechanical strains, but, most importantly, they
      facilitate very efficiently the integration of cell structure and function, thus
      providing the necessary scaffolds for optimal cellular responses upon biochemical
      stresses and protecting against cell death, disease, and aging.

PMID- 29196435
TI  - Leaving the Bench and Finding Your Foundation.
AB  - Scientists who leave the laboratory bench to work for biomedical foundations
      mobilize and focus resources on the most promising research behind a foundation's
      mission. They acquire a broad view of a field, interact closely with research
      scientists at meetings and laboratory visits, and often manage proposal review
      boards and monitor grant progress. Increasingly, scientists at foundations also
      have a more active role in catalyzing research: They are involved in organizing
      targeted workshops, setting research priorities, and directly creating and
      managing resources for a scientific community. They often work closely with
      patient advocacy groups, contract research organizations, government funders and
      regulators, and biotech and pharmaceutical companies.Job opportunities in
      foundations are highly varied, reflecting the diversity of foundations and
      missions. For example, some foundations have general missions to support broad
      basic scientific research, whereas others focus specifically on a particular
      disease and may require different skills. Most scientific positions at
      foundations require a PhD or MD and often some postdoctoral or other experience,
      although not all do. Foundations often lack the clear career path that an
      academic position offers (various levels of professorship, tenure, etc.),
      although there is often significant potential for growth in responsibilities in
      terms of managing science, people, and budgets. Jobs in foundations can be
      challenging yet extremely rewarding, especially for those with broad interests
      and goal-oriented personalities. Many at foundations feel that they have the
      potential to have an even greater impact than if they had stayed at the bench.

PMID- 29196436
TI  - Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised
      phase 3 study.
AB  - OBJECTIVE: Compare efficacy and safety of vonoprazan and lansoprazole for
      secondary prevention of low-dose aspirin (LDA)-associated peptic ulcers in a 24
      week study and long-term extension therapy in separate study. DESIGN: Double
      blind, randomised, non-inferiority study; single-blind extension study at 104
      Japanese sites, including 621 patients (439 in extension) with a history of
      peptic ulcers who required long-term LDA therapy. Randomised (1:1:1, computer
      generated) patients received lansoprazole 15 mg (n=217), vonoprazan 10 mg (n=202)
      or vonoprazan 20 mg (n=202) once daily for 24 weeks (double blind) and <=2 years
      (extension). The following measurements were made: 24-week (primary outcome;
      double blind) and 12-week peptic ulcer recurrence rate, 24-week GI bleeding rate,
      cumulative incidences of peptic ulcer recurrence and GI bleeding, treatment
      emergent adverse events, laboratory results, serum gastrin and pepsinogen I/II
      concentrations. RESULTS: The 24-week peptic ulcer recurrence rate was 2.8%, 0.5%
      and 1.5% in the lansoprazole 15 mg, vonoprazan 10 mg and vonoprazan 20 mg groups,
      respectively. Vonoprazan was non-inferior (Farrington and Manning test: margin
      8.7%, significance level 2.5%) to lansoprazole. In the post hoc analyses of the
      extension study, peptic ulcer recurrence rates were significantly lower with
      vonoprazan 10 mg (log-rank test, P=0.039), but not vonoprazan 20 mg (P=0.260),
      compared with lansoprazole 15 mg. GI bleeding rates were higher with lansoprazole
      compared with two doses of vonoprazan in both 24-week study and extension study.
      CONCLUSION: Vonoprazan (10 and 20 mg) was as effective as lansoprazole (15 mg) in
      preventing peptic ulcer recurrence during LDA therapy, had a similar long-term
      safety profile and was well tolerated. TRIAL REGISTRATION NUMBERS: NCT01452763;
      NCT01456247.

PMID- 29196438
TI  - HBV infection and HCC: the 'dangerous liaisons'.

PMID- 29196440
TI  - Report on the Third FDA-AACR Oncology Dose-Finding Workshop.
AB  - The FDA-AACR Oncology Dose-Finding Workshop, Part 3, was held in Washington, DC,
      on July 20, 2017, as a continuation of the previous two collaborative dose
      finding and optimization workshops presented by the FDA and AACR. This year's
      workshop focused on combination therapy with immune-oncology agents and best
      practices regarding patient and dose selection, predictive biomarkers, and novel
      clinical endpoints. This summary highlights viewpoints that emerged during the
      workshop. Cancer Immunol Res; 5(12); 1058-61. (c)2017 AACR.

PMID- 29196442
TI  - Nephron progenitor cell death elicits a limited compensatory response associated
      with interstitial expansion in the neonatal kidney.
AB  - The final nephron number in an adult kidney is regulated by nephron progenitor
      cell availability and collecting duct branching in the fetal period. Fetal
      environmental perturbations that cause reductions in cell numbers in these two
      compartments result in low nephron endowment. Previous work has shown that
      maternal dietary factors influence nephron progenitor cell availability, with
      both caloric restriction and protein deprivation leading to reduced cell numbers
      through apoptosis. In this study, we evaluate the consequences of inducing
      nephron progenitor cell death on progenitor niche dynamics and on nephron
      endowment. Depletion of approximately 40% of nephron progenitor cells by
      expression of diphtheria toxin A at embryonic day 15 in the mouse results in 10
      20% nephron reduction in the neonatal period. Analysis of cell numbers within the
      progenitor cell pool following induction of apoptosis reveals a compensatory
      response in which surviving progenitor cells increase their proliferation and
      replenish the niche. The proliferative response is temporally associated with
      infiltration of macrophages into the nephrogenic zone. Colony stimulating factor
      1 (CSF1) has a mitogenic effect on nephron progenitor cells, providing a
      potential explanation for the compensatory proliferation. However, CSF1 also
      promotes interstitial cell proliferation, and the compensatory response is
      associated with interstitial expansion in recovering kidneys which can be
      pharmacologically inhibited by treatment with clodronate liposomes. Our findings
      suggest that the fetal kidney employs a macrophage-dependent compensatory
      regenerative mechanism to respond to acute injury caused by death of nephron
      progenitor cells, but that this regenerative response is associated with neonatal
      interstitial expansion.

PMID- 29196437
TI  - Targeting both tumour-associated CXCR2+ neutrophils and CCR2+ macrophages
      disrupts myeloid recruitment and improves chemotherapeutic responses in
      pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: Chemokine pathways are co-opted by pancreatic adenocarcinoma (PDAC) to
      facilitate myeloid cell recruitment from the bone marrow to establish an
      immunosuppressive tumour microenvironment (TME). Targeting tumour-associated
      CXCR2+neutrophils (TAN) or tumour-associated CCR2+ macrophages (TAM) alone
      improves antitumour immunity in preclinical models. However, a compensatory
      influx of an alternative myeloid subset may result in a persistent
      immunosuppressive TME and promote therapeutic resistance. Here, we show CCR2 and
      CXCR2 combined blockade reduces total tumour-infiltrating myeloids, promoting a
      more robust antitumour immune response in PDAC compared with either strategy
      alone. METHODS: Blood, bone marrow and tumours were analysed from PDAC patients
      and controls. Treatment response and correlative studies were performed in mice
      with established orthotopic PDAC tumours treated with a small molecule CCR2
      inhibitor (CCR2i) and CXCR2 inhibitor (CXCR2i), alone and in combination with
      chemotherapy. RESULTS: A systemic increase in CXCR2+ TAN correlates with poor
      prognosis in PDAC, and patients receiving CCR2i showed increased tumour
      infiltrating CXCR2+ TAN following treatment. In an orthotopic PDAC model, CXCR2
      blockade prevented neutrophil mobilisation from the circulation and augmented
      chemotherapeutic efficacy. However, depletion of either CXCR2+ TAN or CCR2+ TAM
      resulted in a compensatory response of the alternative myeloid subset,
      recapitulating human disease. This was overcome by combined CCR2i and CXCR2i,
      which augmented antitumour immunity and improved response to FOLFIRINOX
      chemotherapy. CONCLUSION: Dual targeting of CCR2+ TAM and CXCR2+ TAN improves
      antitumour immunity and chemotherapeutic response in PDAC compared with either
      strategy alone.

PMID- 29196443
TI  - Modelling glioblastoma tumour-host cell interactions using adult brain
      organotypic slice co-culture.
AB  - Glioblastoma multiforme (GBM) is an aggressive incurable brain cancer. The cells
      that fuel the growth of tumours resemble neural stem cells found in the
      developing and adult mammalian forebrain. These are referred to as glioma stem
      cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic
      states: dormant, quiescent, proliferative and differentiating. How environmental
      cues within the brain influence these distinct states is not well understood.
      Laboratory models of GBM can be generated using either genetically engineered
      mouse models, or via intracranial transplantation of cultured tumour initiating
      cells (mouse or human). Unfortunately, these approaches are expensive, time
      consuming, low-throughput and ill-suited for monitoring live cell behaviours.
      Here, we explored whole adult brain coronal organotypic slices as an alternative
      model. Mouse adult brain slices remain viable in a serum-free basal medium for
      several weeks. GSCs can be easily microinjected into specific anatomical sites ex
      vivo, and we demonstrate distinct responses of engrafted GSCs to diverse
      microenvironments in the brain tissue. Within the subependymal zone - one of the
      adult neural stem cell niches - injected tumour cells could effectively engraft
      and respond to endothelial niche signals. Tumour-transplanted slices were treated
      with the antimitotic drug temozolomide as proof of principle of the utility in
      modelling responses to existing treatments. Engraftment of mouse or human GSCs
      onto whole brain coronal organotypic brain slices therefore provides a
      simplified, yet flexible, experimental model. This will help to increase the
      precision and throughput of modelling GSC-host brain interactions and complements
      ongoing in vivo studies. This article has an associated First Person interview
      with the first author of the paper.

PMID- 29196445
TI  - Supplement-Iron Screening and Supplementation in Iron-Replete Pregnant Women and
      Young Children TOC link.

PMID- 29196446
TI  - Erratum for Zyba et al. A moderate increase in dietary zinc reduces DNA strand
      breaks in leukocytes and alters plasma proteins without changing plasma zinc
      concentrations. Am J Clin Nutr 2017;105:343-51.

PMID- 29196444
TI  - Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of
      febrile seizures.
AB  - Complex febrile seizures during infancy constitute an important risk factor for
      development of epilepsy. However, little is known about the alterations induced
      by febrile seizures that make the brain susceptible to epileptic activity. In
      this context, the use of animal models of hyperthermic seizures (HS) could allow
      the temporal analysis of brain molecular changes that arise after febrile
      seizures. Here, we investigated temporal changes in hippocampal gene coexpression
      networks during the development of rats submitted to HS. Total RNA samples were
      obtained from the ventral hippocampal CA3 region at four time points after HS at
      postnatal day (P) 11 and later used for gene expression profiling. Temporal
      endpoints were selected for investigating the acute (P12), latent (P30 and P60)
      and chronic (P120) stages of the HS model. A weighted gene coexpression network
      analysis was used to characterize modules of coexpressed genes, as these modules
      might contain genes with similar functions. The transcriptome analysis pipeline
      consisted of building gene coexpression networks, identifying network modules and
      hubs, performing gene-trait correlations and examining changes in module
      connectivity. Modules were functionally enriched to identify functions associated
      with HS. Our data showed that HS induce changes in developmental, cell adhesion
      and immune pathways, such as Wnt, Hippo, Notch, Jak-Stat and Mapk. Interestingly,
      modules involved in cell adhesion, neuronal differentiation and synaptic
      transmission were activated as early as 1 day after HS. These results suggest
      that HS trigger transcriptional alterations that could lead to persistent
      neurogenesis, tissue remodeling and inflammation in the CA3 hippocampus, making
      the brain prone to epileptic activity.

PMID- 29196448
TI  - Trust fined L333 000 over the deaths of five patients from falls.

PMID- 29196449
TI  - Sustained T follicular helper cell response is essential for control of chronic
      viral infection.
AB  - During chronic viral infections, both CD8 and CD4 T cell responses are
      functionally compromised. Alongside exhaustion of CD8 T cells during chronic
      viral infections, it has also been documented that the CD4 T cells have an
      increased propensity to differentiate toward CXCR5+ T follicular helper cell
      (TFH) lineage. Whether these TFH cells contribute to the immune response to
      chronic viral infection has remained unclear. Using chronic lymphocytic
      choriomeningitis virus (LCMV) infection in conjunction with an in vivo system
      where TFH cells can be conditionally ablated, we have established that these TFH
      cells do in fact play an important protective function. Specifically, we
      demonstrate that these TFH cells are essential for the late emergence of
      neutralizing LCMV-specific antibodies that keep viral titers in check and
      ultimately allow mice to clear the virus. By supporting the generation of
      neutralizing antibodies, we show that sustained activity of TFH cells promotes
      control of the chronic infection in face of exhausted CD8 T cell responses.

PMID- 29196451
TI  - Late arising T follicular helper cells cultivate the B cell crop during chronic
      infections.
AB  - Follicular helper CD4+ T cells are essential for the development of neutralizing
      antibodies that contain chronic viral infection.

PMID- 29196450
TI  - Migratory CD11b+ conventional dendritic cells induce T follicular helper cell
      dependent antibody responses.
AB  - T follicular helper (Tfh) cells are a subset of CD4+ T cells that promote
      antibody production during vaccination. Conventional dendritic cells (cDCs)
      efficiently prime Tfh cells; however, conclusions regarding which cDC instructs
      Tfh cell differentiation have differed between recent studies. We found that
      these discrepancies might exist because of the unusual sites used for
      immunization in murine models, which differentially bias which DC subsets access
      antigen. We used intranasal immunization as a physiologically relevant route of
      exposure that delivers antigen to all tissue DC subsets. Using a combination of
      mice in which the function of individual DC subsets is impaired and different
      antigen formulations, we determined that CD11b+ migratory type 2 cDCs (cDC2s) are
      necessary and sufficient for Tfh induction. DC-specific deletion of the guanine
      nucleotide exchange factor DOCK8 resulted in an isolated loss of CD11b+ cDC2, but
      not CD103+ cDC1, migration to lung-draining lymph nodes. Impaired cDC2 migration
      or development in DC-specific Dock8 or Irf4 knockout mice, respectively, led to
      reduced Tfh cell priming, whereas loss of CD103+ cDC1s in Batf3-/- mice did not.
      Loss of cDC2-dependent Tfh cell priming impaired antibody-mediated protection
      from live influenza virus challenge. We show that migratory cDC2s uniquely carry
      antigen into the subanatomic regions of the lymph node where Tfh cell priming
      occurs-the T-B border. This work identifies the DC subset responsible for Tfh
      cell-dependent antibody responses, particularly when antigen dose is limiting or
      is encountered at a mucosal site, which could ultimately inform the formulation
      and delivery of vaccines.

PMID- 29196452
TI  - Constant attack on T cell lymphomas.
AB  - A proof-of-principle study generates CAR-T cells against T cell lymphoma by
      selectively targeting the T cell receptor beta-chain constant region 1.

PMID- 29196453
TI  - Physician Preferences Surrounding Urinary Tract Infection Management in Neonates.
AB  - OBJECTIVES: Variability exists in the treatment of neonates with urinary tract
      infection (UTI), potentially reflecting an overuse of resources. A cross
      sectional vignette survey was designed to examine variability in physician
      preferences for intravenous (IV) antibiotic duration, genitourinary imaging, and
      prophylactic antibiotics and to evaluate drivers of resource use. METHODS: The
      survey was administered to a random sample of pediatricians through the American
      Medical Association's Physician Masterfile. Respondents were provided with a case
      vignette of a 2-week-old neonate with a febrile UTI and asked to indicate
      preferences for IV antibiotic duration and rank drivers of this decision.
      Respondents were also asked whether they would obtain a voiding cystourethrogram
      (VCUG) and, regardless of preference, randomly presented with a normal result or
      bilateral grade II vesicoureteral reflux. The survey was delivered electronically
      to facilitate skip logic and randomization. RESULTS: A total of 279 surveys were
      completed. Preference for total IV antibiotic duration differed significantly (P
      < .001) across specialty, with a median duration of 2 days for general
      pediatricians/hospitalists, 7 days for neonatologists, and 5 days for infectious
      disease pediatricians. For the 47% (n = 131) who did not want a VCUG, 24/61 (39%)
      wanted prophylactic antibiotics when presented with grade II vesicoureteral
      reflux (P < .001). CONCLUSIONS: Subspecialty status appeared to be the most
      influential driver of IV antibiotic duration in the treatment of UTI. A
      substantial proportion of pediatricians who initially expressed a preference
      against ordering a VCUG wished to prescribe prophylactic antibiotics when results
      were abnormal, which suggests that even unwanted diagnostic test results drive
      treatment decisions.

PMID- 29196454
TI  - Infants With Febrile Urinary Tract Infections and Length of Antibiotic Therapy: A
      Commentary.

PMID- 29196456
TI  - Deep Coverage Tissue and Cellular Proteomics Revealed IL-1beta Can Independently
      Induce the Secretion of TNF-Associated Proteins from Human Synoviocytes.
AB  - Synovitis is a key contributor to the inflammatory environment in osteoarthritis
      (OA) joints. Currently, the biological therapy of OA is not satisfactory in
      multiple single-target trials on anti-TNF agents, or IL-1 antagonists. Systems
      biological understanding of the phosphorylation state in OA synovium is warranted
      to direct further therapeutic strategies. Therefore, in this study, we compared
      the human synovial phosphoproteome of the OA with the acute joint fracture
      subjects. We found that OA synovium had significantly more phosphoproteins, and
      82 phosphoproteins could only be specifically found in all the OA samples.
      Differentially expressed proteins of the OA synovium were focusing on endoplasmic
      reticulum-/Golgi-associated secretion and negative regulation of cell
      proliferation, which was verified through an IL-1beta-treated human synoviocyte
      (HS) in vitro model. With data-independent acquisition-based mass spectrometry,
      we found that IL-1beta could induce HS to secrete proteins that were
      significantly associated with the endosomal/vacuolar pathway, endoplasmic
      reticulum/Golgi secretion, complement activation, and collagen degradation.
      Especially, we found that while specifically suppressing HS endocytosis, IL-1beta
      could activate the secretion of 25 TNF-associated proteins, and the change of
      SERPINE2 and COL3A1 secretion was verified by immunoblotting. In conclusion, our
      results suggest that OA synovium has a polarized phosphoproteome to inhibit
      proliferation and maintain active secretion of HS, whereas IL-1beta alone can
      transform HS to produce a synovitis-associated secretome, containing numerous TNF
      associated secretory proteins in a TNF-independent mode.

PMID- 29196457
TI  - A High-Throughput Real-Time Imaging Technique To Quantify NETosis and Distinguish
      Mechanisms of Cell Death in Human Neutrophils.
AB  - Neutrophils play a key role in host defenses and have recently been implicated in
      the pathogenesis of autoimmune diseases by various mechanisms, including
      formation of neutrophil extracellular traps through a recently described distinct
      form of programmed cell death called NETosis. Techniques to assess and quantitate
      NETosis in an unbiased, reproducible, and efficient way are lacking, considerably
      limiting the advancement of research in this field. We optimized and validated, a
      new method to automatically quantify the percentage of neutrophils undergoing
      NETosis in real time using the IncuCyte ZOOM imaging platform and the membrane
      permeability properties of two DNA dyes. Neutrophils undergoing NETosis induced
      by various physiological stimuli showed distinct changes, with a loss of
      multilobulated nuclei, as well as nuclear decondensation followed by membrane
      compromise, and were accurately counted by applying filters based on fluorescence
      intensity and nuclear size. Findings were confirmed and validated with the
      established method of immunofluorescence microscopy. The platform was also
      validated to rapidly assess and quantify the dose-dependent effect of inhibitors
      of NETosis. In addition, this method was able to distinguish among neutrophils
      undergoing NETosis, apoptosis, or necrosis based on distinct changes in nuclear
      morphology and membrane integrity. The IncuCyte ZOOM platform is a novel real
      time assay that quantifies NETosis in a rapid, automated, and reproducible way,
      significantly optimizing the study of neutrophils. This platform is a powerful
      tool to assess neutrophil physiology and NETosis, as well as to swiftly develop
      and test novel neutrophil targets.

PMID- 29196458
TI  - Integrin alpha4beta7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in
      Blood and Mucosal Tissues of Naive Rhesus Macaques.
AB  - Infusion of a simianized anti-alpha4beta7 mAb (Rh-alpha4beta7) just before and
      following SIV infection protected rhesus macaques from developing AIDS and
      partially from vaginal SIV acquisition. Recently, short-term treatment with Rh
      alpha4beta7 in combination with cART was found to lead to prolonged viral
      suppression after withdrawal of all therapeutic interventions. The humanized form
      of Rh-alpha4beta7, vedolizumab, is a highly effective treatment for inflammatory
      bowel disease. To clarify the mechanism of action of Rh-alpha4beta7, naive
      macaques were infused with Rh-alpha4beta7 and sampled in blood and tissues before
      and after treatment to monitor several immune cell subsets. In blood, Rh
      alpha4beta7 increased the CD4+ and CD8+ T cell counts, but not B cell counts, and
      preferentially increased CCR6+ subsets while decreasing CD103+ and CD69+
      lymphocytes. In mucosal tissues, surprisingly, Rh-alpha4beta7 did not impact
      integrin alpha4+ cells, but decreased the frequencies of CCR6+ and CD69+ CD4+ T
      cells and, in the gut, Rh-alpha4beta7 transiently decreased the frequency of
      memory and IgA+ B cells. In summary, even in the absence of inflammation, Rh
      alpha4beta7 impacted selected immune cell subsets in different tissues. These
      data provide new insights into the mechanisms by which Rh-alpha4beta7 may mediate
      its effect in SIV-infected macaques with implications for understanding the
      effect of treatment with vedolizumab in patients with inflammatory bowel disease.

PMID- 29196459
TI  - Role of CD44 in Regulating TLR2 Activation of Human Macrophages and Downstream
      Expression of Proinflammatory Cytokines.
AB  - Osteoarthritis (OA) is a low-grade chronic inflammatory joint disease. Innate
      immunity contributes to OA progression, mediated by TLR2 and TLR4. We evaluated
      the role of cluster determinant 44 (CD44), a transmembrane glycoprotein, in
      regulating TLR2-linked macrophage activation and resultant proinflammatory
      responses. TLR2 stimulation was performed on differentiated THP-1 macrophages in
      the presence or absence of a CD44-specific Ab or hyaluronan (HA). NF-kappaB
      nuclear translocation, IL-1 beta and TNF-alpha gene expression, and protein
      concentrations were determined. Anti-CD44 Ab and HA treatments reduced NF-kappaB
      translocation, IL-1beta and TNF-alpha expression, and production (p < 0.001).
      Inhibition of proinflammatory response in macrophages by HA was mediated by CD44.
      Protein phosphatase 2A mediated the reduction in NF-kappaB translocation by HA.
      CD44 knockdown reduced NF-kappaB nuclear translocation and downstream IL-1beta
      and TNF-alpha protein production following TLR2 receptor stimulation (p < 0.001).
      CD44+/+ murine bone marrow-derived macrophages produced higher TNF-alpha compared
      with CD44-/- macrophages following TLR2 stimulation (p < 0.01). HA dose
      dependently inhibited TLR2-induced TNF-alpha production by murine bone marrow
      derived macrophages (p < 0.001). OA synovial fluids (SF) stimulated TLR2 and TLR4
      receptors and induced NF-kappaB translocation in THP-1 macrophages. Anti-CD44 Ab
      treatment significantly reduced macrophage activation by OA SF (p < 0.01). CD44
      regulated TLR2 responses in human macrophages, whereby a reduction in CD44 levels
      or engagement of CD44 by its ligand (HA) or a CD44-specific Ab reduced NF-kappaB
      translocation and downstream proinflammatory cytokine production. A CD44-specific
      Ab reduced macrophage activation by OA SF, and CD44 is a potentially novel target
      in OA treatment.

PMID- 29196461
TI  - miRNA suppression of a Notch repressor directs non-neuronal fate in Drosophila
      mechanosensory organs.
AB  - Although there is abundant evidence that individual microRNA (miRNA) loci repress
      large cohorts of targets, large-scale knockout studies suggest that most miRNAs
      are phenotypically dispensable. Here, we identify a rare case of developmental
      cell specification that is highly dependent on miRNA control of an individual
      target. We observe that binary cell fate choice in the Drosophila melanogaster
      peripheral sensory organ lineage is controlled by the non-neuronally expressed
      mir-279/996 cluster, with a majority of notum sensory organs exhibiting
      transformation of sheath cells into ectopic neurons. The mir-279/996 defect
      phenocopies Notch loss of function during the sheath-neuron cell fate decision,
      suggesting the miRNAs facilitate Notch signaling. Consistent with this, mir
      279/996 knockouts are strongly enhanced by Notch heterozygosity, and activated
      nuclear Notch is impaired in the miRNA mutant. Although Hairless (H) is the
      canonical nuclear Notch pathway inhibitor, and H heterozygotes exhibit bristle
      cell fate phenotypes reflecting gain-of-Notch signaling, H/+ does not rescue mir
      279/996 mutants. Instead, we identify Insensible (Insb), another neural nuclear
      Notch pathway inhibitor, as a critical direct miR-279/996 target. Insb is
      posttranscriptionally restricted to neurons by these miRNAs, and its
      heterozygosity strongly suppresses ectopic peripheral nervous system neurons in
      mir-279/996 mutants. Thus, proper assembly of multicellular mechanosensory organs
      requires a double-negative circuit involving miRNA-mediated suppression of a
      Notch repressor to assign non-neuronal cell fate.

PMID- 29196460
TI  - Microglia in Alzheimer's disease.
AB  - Proliferation and activation of microglia in the brain, concentrated around
      amyloid plaques, is a prominent feature of Alzheimer's disease (AD). Human
      genetics data point to a key role for microglia in the pathogenesis of AD. The
      majority of risk genes for AD are highly expressed (and many are selectively
      expressed) by microglia in the brain. There is mounting evidence that microglia
      protect against the incidence of AD, as impaired microglial activities and
      altered microglial responses to beta-amyloid are associated with increased AD
      risk. On the other hand, there is also abundant evidence that activated microglia
      can be harmful to neurons. Microglia can mediate synapse loss by engulfment of
      synapses, likely via a complement-dependent mechanism; they can also exacerbate
      tau pathology and secrete inflammatory factors that can injure neurons directly
      or via activation of neurotoxic astrocytes. Gene expression profiles indicate
      multiple states of microglial activation in neurodegenerative disease settings,
      which might explain the disparate roles of microglia in the development and
      progression of AD pathology.

PMID- 29196462
TI  - p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by
      phosphorylating ULK1.
AB  - Inflammation and autophagy are two critical cellular processes. The relationship
      between these two processes is complex and includes the suppression of
      inflammation by autophagy. However, the signaling mechanisms that relieve this
      autophagy-mediated inhibition of inflammation to permit a beneficial inflammatory
      response remain unknown. We find that LPS triggers p38alpha mitogen-activated
      protein kinase (MAPK)-dependent phosphorylation of ULK1 in microglial cells. This
      phosphorylation inhibited ULK1 kinase activity, preventing it from binding to the
      downstream effector ATG13, and reduced autophagy in microglia. Consistently,
      p38alpha MAPK activity is required for LPS-induced morphological changes and the
      production of IL-1beta by primary microglia in vitro and in the brain, which
      correlates with the p38alpha MAPK-dependent inhibition of autophagy. Furthermore,
      inhibition of ULK1 alone was sufficient to promote an inflammatory response in
      the absence of any overt inflammatory stimulation. Thus, our study reveals a
      molecular mechanism that enables the initial TLR4-triggered signaling pathway to
      inhibit autophagy and optimize inflammatory responses, providing new
      understanding into the mechanistic basis of the neuroinflammatory process.

PMID- 29196463
TI  - Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer.
AB  - "Liquid biopsy" approaches analyzing cell-free DNA (cfDNA) from the blood of
      patients with cancer are increasingly utilized in clinical practice. However, it
      is not yet known whether cfDNA sequencing from large cohorts of patients with
      cancer can detect genomic alterations at frequencies similar to those observed by
      direct tumor sequencing, and whether this approach can generate novel insights.
      Here, we report next-generation sequencing data from cfDNA of 1,397 patients with
      colorectal cancer. Overall, frequencies of genomic alterations detected in cfDNA
      were comparable to those observed in three independent tissue-based colorectal
      cancer sequencing compendia. Our analysis also identified a novel cluster of
      extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking
      binding of anti-EGFR antibodies. Patients with EGFR ECD mutations displayed
      striking tumor heterogeneity, with 91% harboring multiple distinct resistance
      alterations (range, 1-13; median, 4). These results suggest that cfDNA profiling
      can effectively define the genomic landscape of cancer and yield important
      biological insights.Significance: This study provides one of the first examples
      of how large-scale genomic profiling of cfDNA from patients with colorectal
      cancer can detect genomic alterations at frequencies comparable to those observed
      by direct tumor sequencing. Sequencing of cfDNA also generated insights into
      tumor heterogeneity and therapeutic resistance and identified novel EGFR
      ectodomain mutations. Cancer Discov; 8(2); 164-73. (c)2017 AACR.This article is
      highlighted in the In This Issue feature, p. 127.

PMID- 29196464
TI  - Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix
      Response in Human Cancers.
AB  - We have profiled, for the first time, an evolving human metastatic
      microenvironment by measuring gene expression, matrisome proteomics, cytokine and
      chemokine levels, cellularity, extracellular matrix organization, and
      biomechanical properties, all on the same sample. Using biopsies of high-grade
      serous ovarian cancer metastases that ranged from minimal to extensive disease,
      we show how nonmalignant cell densities and cytokine networks evolve with disease
      progression. Multivariate integration of the different components allowed us to
      define, for the first time, gene and protein profiles that predict extent of
      disease and tissue stiffness, while also revealing the complexity and dynamic
      nature of matrisome remodeling during development of metastases. Although we
      studied a single metastatic site from one human malignancy, a pattern of
      expression of 22 matrisome genes distinguished patients with a shorter overall
      survival in ovarian and 12 other primary solid cancers, suggesting that there may
      be a common matrix response to human cancer.Significance: Conducting multilevel
      analysis with data integration on biopsies with a range of disease involvement
      identifies important features of the evolving tumor microenvironment. The data
      suggest that despite the large spectrum of genomic alterations, some human
      malignancies may have a common and potentially targetable matrix response that
      influences the course of disease. Cancer Discov; 8(3); 304-19. (c)2017 AACR.This
      article is highlighted in the In This Issue feature, p. 253.

PMID- 29196470
TI  - Endobronchial epithelial-myoepithelial carcinoma of the lung.

PMID- 29196474
TI  - Inflammasome activation and assembly at a glance.
AB  - Inflammasomes are multimeric protein complexes that typically comprise a sensor,
      an adaptor and the zymogen procaspase-1. An inflammasome assembles in response to
      a diverse range of pathogen-associated or danger-associated molecular patterns
      (PAMPs or DAMPs). The inflammasome platform leads to activation of caspase-1
      through proximity-induced self-cleavage, which further induces maturation of
      interleukins 1beta and 18 (IL-1beta and IL-18) through proteolytic cleavage of
      pro-IL-1beta and pro-IL-18. Activated caspase-1 also cleaves gasdermin D, which
      leads to a particular form of cell death called pyroptosis. Mutations in genes
      that encode inflammasome components are associated with many inflammatory
      disorders, and studies in the past decade have highlighted the importance of
      appropriate activation of the inflammasome in homeostasis and disease
      pathogenesis. Therefore, much attention is being paid to uncover the modulators
      and regulators of inflammasome assembly and pyroptosis. This Cell Science at a
      Glance article and accompanying poster outlines the concepts in the activation of
      inflammasome sensors and assembly of the inflammasome platform. We also discuss
      recent insights into the mechanisms of regulation of inflammasome activity and
      the induction of cell death by pyroptosis.

PMID- 29196475
TI  - FYCO1 regulates accumulation of post-mitotic midbodies by mediating LC3-dependent
      midbody degradation.
AB  - The post-mitotic midbody (MB) is a remnant of cytokinesis that can be
      asymmetrically inherited by one of the daughter cells following cytokinesis.
      Until recently, the MB was thought to be degraded immediately following
      cytokinesis. However, recent evidence suggests that the MB is a protein-rich
      organelle that accumulates in stem cell and cancer cell populations, indicating
      that it may have post-mitotic functions. Here, we investigate the role of FYCO1,
      an LC3-binding protein (herein, LC3 refers to MAP1LC3B), and its function in
      regulating the degradation of post-mitotic MBs. We show that FYCO1 is responsible
      for formation of LC3-containing membrane around the post-mitotic MB and that
      FYCO1 knockdown increases MB accumulation. Although MBs accumulate in the stem
      cell-like population of squamous cell carcinomas, FYCO1 depletion does not affect
      the clonogenicity of these cells. Instead, MB accumulation leads to an increase
      in anchorage-independent growth and invadopodia formation in HeLa cells and
      squamous carcinoma cells. Collectively, our data suggest that FYCO1 regulates MB
      degradation, and we present the first evidence that cancer invasiveness is a
      feature that can be modulated by the accumulation of MBs in cancer stem
      cells.This article has an associated First Person interview with the first author
      of the paper.

PMID- 29196477
TI  - Usage of unscheduled hospital care by homeless individuals in Dublin, Ireland: a
      cross-sectional study.
AB  - OBJECTIVES: Homeless people lack a secure, stable place to live and experience
      higher rates of serious illness than the housed population. Studies, mainly from
      the USA, have reported increased use of unscheduled healthcare by homeless
      individuals.We sought to compare the use of unscheduled emergency department (ED)
      and inpatient care between housed and homeless hospital patients in a high-income
      European setting in Dublin, Ireland. SETTING: A large university teaching
      hospital serving the south inner city in Dublin, Ireland. Patient data are
      collected on an electronic patient record within the hospital. PARTICIPANTS: We
      carried out an observational cross-sectional study using data on all ED visits
      (n=47 174) and all unscheduled admissions under the general medical take (n=7031)
      in 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The address field of the
      hospital's electronic patient record was used to identify patients living in
      emergency accommodation or rough sleeping (hereafter referred to as homeless).
      Data on demographic details, length of stay and diagnoses were extracted.
      RESULTS: In comparison with housed individuals in the hospital catchment area,
      homeless individuals had higher rates of ED attendance (0.16 attendances per
      person/annum vs 3.0 attendances per person/annum, respectively) and inpatient bed
      days (0.3 vs 4.4 bed days/person/annum). The rate of leaving ED before assessment
      was higher in homeless individuals (40% of ED attendances vs 15% of ED
      attendances in housed individuals). The mean age of homeless medical inpatients
      was 44.19 years (95% CI 42.98 to 45.40), whereas that of housed patients was
      61.20 years (95% CI 60.72 to 61.68). Homeless patients were more likely to
      terminate an inpatient admission against medical advice (15% of admissions vs 2%
      of admissions in homeless individuals). CONCLUSION: Homeless patients represent a
      significant proportion of ED attendees and medical inpatients. In contrast to
      housed patients, the bulk of usage of unscheduled care by homeless people occurs
      in individuals aged 25-65 years.

PMID- 29196476
TI  - Changes in older people's care profiles during the last 2 years of life, 1996
      1998 and 2011-2013: a retrospective nationwide study in Finland.
AB  - OBJECTIVES: The time of death is increasingly postponed to a very high age. How
      this change affects the use of care services at the population level is unknown.
      This study analyses the care profiles of older people during their last 2 years
      of life, and investigates how these profiles differ for the study years 1996-1998
      and 2011-2013. DESIGN: Retrospective cross-sectional nationwide data drawn from
      the Care Register for Health Care, the Care Register for Social Care and the
      Causes of Death Register. The data included the use of hospital and long-term
      care services during the last 2 years of life for all those who died in 1998 and
      in 2013 at the age of >=70 years in Finland. METHODS: We constructed four care
      profiles using two criteria: (1) number of days in round-the-clock care (vs at
      home) in the last 2 years of life and (2) care transitions during the last 6
      months of life (ie, end-of-life care transitions). RESULTS: Between the study
      periods, the average age at death and the number of diagnoses increased. Most
      older people (1998: 64.3%, 2013: 59.3%) lived at home until their last months of
      life (profile 2) after which they moved into hospital or long-term care
      facilities. This profile became less common and the profiles with a high use of
      care services became more common (profiles 3 and 4 together in 1998: 25.0%, in
      2013: 30.9%). People with dementia, women and the oldest old were over
      represented in the latter profiles. In both study periods, fewer than one in ten
      stayed at home for the whole last 6 months (profile 1). CONCLUSIONS: Postponement
      of death to a very old age may translate into more severe disability in the last
      months or years of life. Care systems must be prepared for longer periods of long
      term care services needed at the end of life.

PMID- 29196478
TI  - Efficacy of hypnotherapy compared to cognitive-behavioural therapy for mild-to
      moderate depression: study protocol of a randomised-controlled rater-blind trial
      (WIKI-D).
AB  - INTRODUCTION: Despite a substantial number of studies providing evidence for the
      efficacy of psychological treatment for mild-to-moderate depression, maximally
      only 50% of participants respond to treatment, even when using gold-standard
      treatments such as cognitive-behavioural therapy (CBT) and interpersonal therapy.
      New approaches such as the 'third wave' psychotherapies have provided promising
      results; however, studies concerning the comparison with evidence-based
      treatments are lacking. This study aims to compare the efficacy of clinical
      hypnotherapy (HT) with gold-standard psychotherapy (CBT) in the treatment of mild
      to-moderate major depressive episodes. METHODS AND ANALYSIS: The present study
      comprises a monocentric, two-armed, randomised-controlled, rater-blind (non
      inferiority) clinical trial. A total of 160 participants with mild-to-moderate
      major depression episode will be randomly assigned to either CBT or HT involving
      20 sessions of psychotherapy over a period of 24 weeks. We predict that the
      average improvement in the Montgomery-Asberg Depression Rating Scale score will
      not be inferior in HT compared with CBT (non-inferiority hypothesis).Further
      outcome parameters will include the number of participants responding to
      treatment following the completion of treatment and 1 year after. Additionally,
      quality of life, treatment expectations and hypnotic susceptibility before and
      after end of treatment will be assessed. ETHICS AND DISSEMINATION: The study
      protocol and the documents for the informed consent have been approved by the
      Ethics Committee of the University Hospital Tuebingen (061/2015B02). The results
      of this trial will be submitted for publication in peer-reviewed journals, and
      will be presented at national and international conferences. TRIAL REGISTRATION
      NUMBER: NCT02375308; Pre-results.

PMID- 29196480
TI  - Is the admission test for a course in medicine a good predictor of academic
      performance? A case-control experience at the school of medicine of Turin.
AB  - OBJECTIVES: The usefulness of university admission tests to medical schools has
      been discussed in recent years. In the academic year 2014-15 in Italy, several
      students who failed the admission test appealed to the regional administrative
      court ('Tribunale Amministrativo Regionale'-TAR) requesting to be included,
      despite their test results, and all were admitted to their respective courses.
      The existence of this population of students generated a control group, in order
      to evaluate the predictive capacity of the admission test. The aim of the present
      work is to discuss the ability of university admission tests to predict
      subsequent academic success. SETTING AND PARTICIPANTS: The study involved 683
      students who enrolled onto the first year of the degree course in medicine in the
      academic year 2014-15 at the University of Turin (Molinette and San Luigi Gonzaga
      colleges). The students were separated into two categories: those who passed the
      admission test (n1=531) and those who did not pass the admission test but won
      their appeal in the TAR (n2=152). OUTCOMES: The validity of the admission test
      was analysed using specificity, sensitivity, positive and negative likelihood
      ratios (LH+, LH-), receiver operating characteristic (ROC) curves, area under the
      ROC curve (AUC), and relative (95% CI). RESULTS: The results showed that the
      admission test appeared to be a good tool for predicting the academic
      performances in the first year of the course (AUC=0.70, 95% CI 0.64 to 0.76).
      Moreover, some subject areas seemed to have a greater discriminating capacity
      than others. In general, students who obtained a high score in scientific
      questions were more likely to obtain the required standards during the first year
      (LH+ 1.22, 95% CI 1.14 to 1.25). CONCLUSIONS: Based on a consistent statistical
      approach, our study seems to confirm the ability of the admission test to predict
      academic success in the first year at the school of medicine of Turin.

PMID- 29196479
TI  - Sleep Treatment Outcome Predictors (STOP) Pilot Study: a protocol for a
      randomised controlled trial examining predictors of change of insomnia symptoms
      and associated traits following cognitive-behavioural therapy for insomnia in an
      unselected sample.
AB  - INTRODUCTION: Cognitive-behavioural therapy for insomnia (CBT-I) leads to
      insomnia symptom improvements in a substantial proportion of patients. However,
      not everyone responds well to this treatment, and it is unclear what determines
      individual differences in response. The broader aim of this work is to examine to
      what extent response to CBT-I is due to genetic and environmental factors. The
      purpose of this pilot study is to examine feasibility of a design to test
      hypotheses focusing on an unselected sample, that is, without selection on
      insomnia complaints, in order to plan a larger behavioural genetics study where
      most participants will likely not have an insomnia disorder. METHODS AND
      ANALYSIS: A two parallel-group randomised controlled trial is being conducted
      across three London universities. Female students (minimum age 18 years) enrolled
      on a psychology programme at one of the three sites were invited to participate.
      The target number of participants to be recruited is 240. Following baseline
      assessments, participants were randomly allocated to either the treatment group,
      where they received weekly sessions of digital CBT-I for 6 weeks, or the control
      group, where they completed an online puzzle each week for 6 weeks. Follow-up
      assessments have taken place mid-intervention (3 weeks) and end of intervention
      (6 weeks). A 6-month follow-up assessment will also occur. Primary outcomes will
      be assessed using descriptive statistics and effect size estimates for
      intervention effects. Secondary outcomes will be analysed using multivariate
      generalised estimating equation models. ETHICS AND DISSEMINATION: The study
      received ethical approval from the Research Ethics and Integrity subcommittee,
      Goldsmiths, University of London (application reference: EA 1305). DNA sample
      collection for the BioResource received ethical approval from the NRES Committee
      South Central-Oxford (reference number: 15/SC/0388). The results of this work
      shall be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:
      NCT03062891; Results.

PMID- 29196481
TI  - Cardiovascular mortality and oral antidiabetic drugs: protocol for a systematic
      review and network meta-analysis.
AB  - INTRODUCTION: Cardiovascular diseases are the leading cause of morbidity and
      mortality among individuals with diabetes. Despite the beneficial effects of
      antidiabetic drugs (ADDs) in terms of lowering haemoglobin A1c, several ADDs have
      been shown to increase the risk of cardiovascular events. Given the high
      prevalence of cardiovascular disease among individuals with diabetes, it is
      important to weigh the benefits of ADDs against their cardiovascular safety.
      Therefore, the objective of the current study is to conduct a systematic review
      with network meta-analysis to compare the effects of different oral
      pharmacological classes of ADDs on cardiovascular safety. METHODS AND ANALYSIS:
      Randomised clinical trials (RCTs) and observational studies published in English
      up to 31 January 2017, and which include direct and/or indirect evidence, will be
      included. Studies will be retrieved by searching four electronic databases and
      cross-referencing. Dual selection and abstraction of data will occur. The primary
      outcome will be cardiovascular mortality. Secondary outcomes will include all
      cause mortality, new event of acute myocardial infarction, stroke (haemorrhagic
      and ischaemic), hospitalisation for acute coronary syndrome and urgent
      revascularisation procedures. Risk of bias will be assessed using the Cochrane
      Risk of Bias assessment instrument for RCTs and the Strengthening the Reporting
      of Observational Studies in Epidemiology instrument for observational studies.
      Network meta-analysis will be performed using multivariate random-effects meta
      regression models. The surface under the cumulative ranking curve will be used to
      provide a hierarchy of ADDs that increase cardiovascular mortality.
      DISSEMINATION: The results of this study will be presented at a professional
      conference and submitted to a peer-reviewed journal. PROSPERO REGISTRATION
      NUMBER: CRD42017051220.

PMID- 29196482
TI  - Do changing levels of maternal exercise during pregnancy affect neonatal
      adiposity? Secondary analysis of the babies after SCOPE: evaluating the
      longitudinal impact using neurological and nutritional endpoints (BASELINE) birth
      cohort (Cork, Ireland).
AB  - OBJECTIVE: To investigate whether changing levels of exercise during pregnancy
      are related to altered neonatal adiposity. DESIGN: Secondary analysis of data
      from a prospective cohort study. SETTING: Cork, Ireland. PARTICIPANTS: 1200
      mother - infant pairs recruited as part of a prospective birth cohort, Babies
      After SCOPE: Evaluating the Longitudinal Impact Using Neurological and
      Nutritional Endpoints (BASELINE). MAIN OUTCOME MEASURES: Neonatal adiposity was
      assessed within several days of birth using air displacement plethysmography
      (PEAPOD). Per cent body fat (BF%) as a continuous outcome and a pair of
      dichotomous variables; high or low adiposity, representing BF% >90th or <10th
      centile, respectively. Multivariable linear and logistic regression models were
      used to investigate the relationship between exercise and the respective
      outcomes. RESULTS: Crude analysis revealed no association between a changing
      level of exercise (since becoming pregnant) at 15 weeks' gestation and any of the
      outcomes (BF%, low adiposity and high adiposity). At 20 weeks' gestation,
      analyses revealed that relative to women who do not change their exercise level
      up to 20 weeks, those women who decreased their exercise level were more likely
      to give birth to a neonate with adiposity above the 90th centile (OR 1.62, 95% CI
      1.07 to 2.46). This association was maintained after adjustment for putative
      confounders (OR 1.62, 95% CI 1.06 to 2.47). CONCLUSIONS: We observed a possible
      critical period for the association between changing exercise levels and neonatal
      adiposity, with no association observed with exercise recall for the first 15
      weeks of gestation, but an association with a decreasing level of exercise
      between 15 and 20 weeks. These results should be interpreted in line with the
      limitations of the study and further studies utilising objectively measured
      estimates of exercise are required in order to replicate these findings. TRIAL
      REGISTRATION NUMBER: NCT01498965.

PMID- 29196483
TI  - Partners at Care Transitions (PACT) -e xploring older peoples' experiences of
      transitioning from hospital to home in the UK: protocol for an observation and
      interview study of older people and their families to understand patient
      experience and involvement in care at transitions.
AB  - INTRODUCTION: Length of hospital inpatient stays have reduced. This benefits
      patients, who prefer to be at home, and hospitals, which can treat more people
      when stays are shorter. Patients may, however, leave hospital sicker, with
      ongoing care needs. The transition period from hospital to home can be risky,
      particularly for older patients with complex health and social needs. Improving
      patient experience, especially through greater patient involvement, may improve
      outcomes for patients and is a key indicator of care quality and safety. In this
      research, we aim to: capture the experiences of older patients and their families
      during the transition from hospital to home, and identify opportunities for
      greater patient involvement in care, particularly where this contributes to
      greater individual-level and organisational-level resilience. METHODS AND
      ANALYSIS: A 'focused ethnography' comprising observations, 'Go-Along' and
      semistructured interviews will be used to capture patient and carer experiences
      during different points in the care transition from admission to 90 days after
      discharge. We will recruit 30 patients and their carers from six hospital
      departments across two National Health Service (NHS) Trusts. Analysis of
      observations and interviews will use a framework approach to identify themes to
      understand the experience of transitions and generate ideas about how patients
      could be more actively involved in their care. This will include exploring what
      'good' care at transitions looks like and seeking out examples of success, as
      well as recommendations for improvement. ETHICS AND DISSEMINATION: Ethical
      approval was received from the NHS Research Ethics Committee in Wales. The
      research findings will add to a growing body of knowledge about patient
      experience of transitions, in particular providing insight into the experiences
      of patients and carers throughout the transitions process, in 'real time'.
      Importantly, the data will be used to inform the development of a patient-centred
      intervention to improve the quality and safety of transitions.

PMID- 29196484
TI  - Effect of herbal extract granules combined with otilonium bromide on irritable
      bowel syndrome with diarrhoea: a study protocol for a randomised controlled
      trial.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS), known as a functional and organic
      gastrointestinal disorder, is a collection of symptoms that occur together and
      generally include pain or discomfort in the abdomen and changes in bowel movement
      patterns. Due to the limitations of conventional treatments, alternative IBS
      treatments are used by many patients worldwide. Samryungbaekchulsan (SRS), a
      herbal formula, has long been used for alleviating diarrhoea-predominant IBS (D
      IBS) in traditional Korean medicine. Otilonium bromide (OB) is an antimuscarinic
      compound used to relieve spasmodic pain in the gut, especially in IBS. Although
      herbal formulae and Western drugs are commonly coadministered for various
      diseases in Korea, few clinical studies have been conducted regarding the
      synergic effects of these treatments for any disease, including D-IBS. METHODS
      AND ANALYSIS: This trial is a randomised, double-blinded, placebo-controlled,
      double-dummy, four-arm, parallel study. After a 2-week preparation period, 80
      patients with D-IBS will be randomly assigned to one of four treatment groups
      consisting of SRS (water extract granules, 5 g/pack, three times a day) with OB
      (tablet form, one capsule three times a day) or their placebos, with treatment
      lasting for 8 weeks. Post-treatment follow-up will be conducted 4 weeks after the
      end of treatment. The primary outcome is the finding obtained using the Subject's
      Global Assessment of Relief method. The secondary outcomes are the severity of
      symptoms related to D-IBS, determined using a 10-point scale, and the change in
      symptoms. ETHICS AND DISSEMINATION: This trial has full ethical approval of the
      Ethics Committee of Catholic Kwandong University International St. Mary's
      Hospital (IS15MISV0033) and the Korean Ministry of Food and Drug Safety (30769).
      The results of the study will be disseminated through a peer-reviewed journal
      and/or conference presentations. TRIAL PROTOCOL VERSION: IS15MISV0033 version 4.0
      (25 July 2016). TRIAL REGISTRATION NUMBER: KCT0001621 (approval date: 10 August
      2015).

PMID- 29196485
TI  - Cluster-randomised controlled trial to assess the effectiveness and cost
      effectiveness of an obesity prevention programme for Chinese primary school-aged
      children: the CHIRPY DRAGON study protocol.
AB  - INTRODUCTION: Childhood obesity in China has increased more rapidly and over a
      shorter time period than in other countries. However, there is a paucity of
      rigorously developed and evaluated prevention interventions. We aim to evaluate
      the clinical and cost-effectiveness as well as the implementation process of a
      complex multicomponent intervention developed using the UK Medical Research
      Council (MRC) framework. This study provides one of the first examples of
      rigorous development and evaluation of a childhood obesity prevention programme
      in a non-western population using the MRC methods. METHODS AND ANALYSIS: A
      cluster-randomised controlled trial in 40 primary schools in Guangzhou, China,
      including children aged 6-7 years at baseline. Schools will be randomly allocated
      to either the usual practice (n=20) or intervention arm (n=20). The 12-month
      intervention consists of four components targeting diet and physical activity
      behaviours in and outside school, with family involvement. The primary objective
      is to compare the difference in mean body mass index (BMI) z-score between the
      intervention and control arms at the end of the intervention (starting
      March/April 2017). A sample size of 1640 pupils recruited from 40 schools is
      sufficient to detect a difference of 0.17 units in the mean BMI z-score with a
      power of 80% (ICC=0.01. ICC, intraclass correlation coefficient) and a
      significance level of 5%. Treatment effects will be tested using a mixed linear
      model in STATA adjusting for the child baseline BMI z-score and clustering by
      school. All analyses will be by intention to treat. Secondary analyses will
      additionally adjust for prespecified school-level and child-level covariates. The
      incremental cost-effectiveness ratio for the intervention versus usual practice
      will be 'cost per quality-adjusted life year (QALY)'. Cost per change in BMI z
      score will also be assessed. A range of methods will be used to evaluate
      intervention implementation, mechanisms of impact and contextual factors. ETHICS
      AND DISSEMINATION: Ethical approval was obtained from the Life and Health
      Sciences Ethical Review Committee at the University of Birmingham and the Ethical
      Committee of Guangzhou Centre for Disease Control and Prevention. The primary,
      secondary, process evaluation and economic evaluation results of the trial will
      be disseminated through relevant international peer-reviewed journals and
      conferences. TRIAL REGISTRATION NUMBER: ISRCTN11867516; Pre-results.

PMID- 29196486
TI  - Multiple and multidimensional transitions from trainee to trained doctor: a
      qualitative longitudinal study in the UK.
AB  - OBJECTIVES: To explore trainee doctors' experiences of the transition to trained
      doctor, we answer three questions: (1) What multiple and multidimensional
      transitions (MMTs) are experienced as participants move from trainee to trained
      doctor? (2) What facilitates and hinders doctors' successful transition
      experiences? (3) What is the impact of MMTs on trained doctors? DESIGN: A
      qualitative longitudinal study underpinned by MMT theory. SETTING: Four training
      areas (health boards) in the UK. PARTICIPANTS: 20 doctors, 19 higher-stage
      trainees within 6 months of completing their postgraduate training and 1 staff
      grade, associate specialist or specialty doctor, were recruited to the 9-month
      longitudinal audio-diary (LAD) study. All completed an entrance interview, 18
      completed LADs and 18 completed exit interviews. METHODS: Data were analysed
      cross-sectionally and longitudinally using thematic Framework Analysis. RESULTS:
      Participants experienced a multiplicity of expected and unexpected, positive and
      negative work-related transitions (eg, new roles) and home-related transitions
      (eg, moving home) during their trainee-trained doctor transition. Factors
      facilitating or inhibiting successful transitions were identified at various
      levels: individual (eg, living arrangements), interpersonal (eg, presence of
      supportive relationships), systemic (eg, mentoring opportunities) and macro (eg,
      the curriculum provided by Medical Royal Colleges). Various impacts of
      transitions were also identified at each of these four levels: individual (eg,
      stress), interpersonal (eg, trainees' children spending more time in childcare),
      systemic (eg, spending less time with patients) and macro (eg, delayed start in
      trainees' new roles). CONCLUSIONS: Priority should be given to developing
      supportive relationships (both formal and informal) to help trainees transition
      into their trained doctor roles, as well as providing more opportunities for
      learning. Further longitudinal qualitative research is now needed with a longer
      study duration to explore transition journeys for several years into the trained
      doctor role.

PMID- 29196487
TI  - Application of time series analysis in modelling and forecasting emergency
      department visits in a medical centre in Southern Taiwan.
AB  - OBJECTIVE: Emergency department (ED) overcrowding is acknowledged as an
      increasingly important issue worldwide. Hospital managers are increasingly paying
      attention to ED crowding in order to provide higher quality medical services to
      patients. One of the crucial elements for a good management strategy is demand
      forecasting. Our study sought to construct an adequate model and to forecast
      monthly ED visits. METHODS: We retrospectively gathered monthly ED visits from
      January 2009 to December 2016 to carry out a time series autoregressive
      integrated moving average (ARIMA) analysis. Initial development of the model was
      based on past ED visits from 2009 to 2016. A best-fit model was further employed
      to forecast the monthly data of ED visits for the next year (2016). Finally, we
      evaluated the predicted accuracy of the identified model with the mean absolute
      percentage error (MAPE). The software packages SAS/ETS V.9.4 and Office Excel
      2016 were used for all statistical analyses. RESULTS: A series of statistical
      tests showed that six models, including ARIMA (0, 0, 1), ARIMA (1, 0, 0), ARIMA
      (1, 0, 1), ARIMA (2, 0, 1), ARIMA (3, 0, 1) and ARIMA (5, 0, 1), were candidate
      models. The model that gave the minimum Akaike information criterion and Schwartz
      Bayesian criterion and followed the assumptions of residual independence was
      selected as the adequate model. Finally, a suitable ARIMA (0, 0, 1) structure,
      yielding a MAPE of 8.91%, was identified and obtained as
      Visitt=7111.161+(at+0.37462 at-1). CONCLUSION: The ARIMA (0, 0, 1) model can be
      considered adequate for predicting future ED visits, and its forecast results can
      be used to aid decision-making processes.

PMID- 29196488
TI  - Antimicrobial prescribing behaviour in dogs and cats by Belgian veterinarians.
AB  - The objective of this study is to survey general prescribing behaviour by Belgian
      companion animal veterinarians and to assess agreement of these practices with
      current treatment guidelines. Therefore an online survey was administered with
      five realistic and frequently occurring first-line cases to primary-care
      veterinary practitioners. For each case a predefined pattern of questions were
      asked about whether or not they would prescribe antimicrobials, if they would
      prescribe a non-antimicrobial treatment and if they would perform additional
      diagnostic steps. The responses were compared with recommendations in national
      guidelines and recent literature. The overall most prescribed antimicrobials were
      potentiated amoxicillin (43.0 per cent), fluoroquinolones (14.7 per cent), third
      generation and fourth-generation cephalosporins (10.9 per cent) and tetracyclines
      (10.9 per cent). Only 48.3 per cent of the veterinarians complied with the
      guidelines in nearly all of the clinical scenarios (ie, prescribing
      antimicrobials when indicated, not prescribing antimicrobials when it is not
      indicated). Moreover, when prescribing highest priority critically important
      antimicrobials, susceptibility testing on bacterial cultures was performed in
      only 12.4 per cent of the prescriptions. The results showed that the prescribing
      behaviour of antimicrobial compounds by primary-care veterinary practitioners in
      dogs and cats is often not in agreement with national guidelines. Focus in
      improvement of this prescribing behaviour should be on performing the appropriate
      diagnostic steps and decreasing the use of highest priority critically important
      antimicrobials.

PMID- 29196489
TI  - HEV infection not evident in rodents on English pig farms.

PMID- 29196490
TI  - Retrospective evaluation of correlation and agreement between two recovery
      scoring systems in horses.

PMID- 29196492
TI  - High-fat diet exposure from pre-pubertal age induces polycystic ovary syndrome
      (PCOS) in rats.
AB  - Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, oligo
      anovulation, polycystic ovaries and metabolic syndrome. Many researchers reported
      that PCOS often starts with menarche in adolescents. Presently available animal
      model focuses on ovarian but not metabolic features of PCOS. Therefore, we
      hypothesized that high-fat diet feeding to pre-pubertal female rats results in
      both reproductive and metabolic features of PCOS. Pre-pubertal female rats were
      divided into two groups: group I received normal pellet diet and group II
      received high-fat diet (HFD). In the letrozole study, adult female rats were
      divided into two groups: group I received 1% carboxy methyl cellulose and group
      II received 1 mg/kg letrozole orally. Oral glucose tolerance test, lipid profile,
      fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight,
      luteinizing hormone (LH) receptor and follicle-stimulating hormone receptor
      expression were measured. Polycystic ovarian morphology was assessed through
      histopathological changes of ovary. Feeding of HFD gradually increase glucose
      intolerance and fasting insulin levels. Triglyceride level was higher in HFD
      study while total cholesterol level was higher in the letrozole study. Alteration
      in testosterone and estrogen levels was observed in both studies. LH receptor
      expression was upregulated only in HFD study. Histopathological changes like
      increase cystic follicle, diminished granulosa cell layer and thickened theca
      cell layer were observed in letrozole as well as HFD study. High-fat diet
      initiated at pre-puberty age in rats produces both metabolic disturbances and
      ovarian changes similar to that observed clinically in PCOS patients. Letrozole
      on the other hand induces change in ovarian structure and function.

PMID- 29196491
TI  - Diversity of Nicotinic Acetylcholine Receptor Positive Allosteric Modulators
      Revealed by Mutagenesis and a Revised Structural Model.
AB  - By combining electrophysiological and computational approaches we have examined a
      series of positive allosteric modulators (PAMs) acting on the human alpha7
      nicotinic acetylcholine receptor (nAChR). Electrophysiological studies have
      focused on three alpha7-selective PAMs (A-867744, TBS-516, and TQS) that display
      similar effects on wild-type alpha7 nAChRs. In addition to potentiating agonist
      evoked responses, all three compounds reduce receptor desensitization and,
      consequently, are classed as type II PAMs. Despite having similar effects on wild
      type receptors, A-867744 was found to have profoundly differing effects on
      mutated receptors compared with TBS-516 and TQS, a finding that is consistent
      with previous studies indicating that A-867744 may have a different mechanism of
      action compare with other alpha7-selective type II PAMs. Due to evidence that
      these PAMs bind within the alpha7 nAChR transmembrane region, we generated and
      validated new structural models of alpha7. Importantly, we have corrected a
      previously identified error in the transmembrane region of the original cryo
      electron microscopy Torpedo model; the only pentameric ligand-gated ion channel
      imaged in a native lipid membrane. Real-space refinement was used to generate
      closed and open conformations on which the alpha7 models were based. Consensus
      docking with an extended series of PAMs with chemical similarity to A-867744, TBS
      516, and TQS suggests that all bind to a broadly similar intersubunit
      transmembrane site. However, differences in the predicted binding of A-867744,
      compared with TBS-516 and TQS, may help to explain the distinct functional
      effects of A-867744. Thus, our revised structural models may provide a useful
      tool for interpreting functional effects of PAMs.

PMID- 29196493
TI  - Intracytoplasmic sperm injection in domestic and wild mammals.
AB  - Intracytoplasmic sperm injection (ICSI) has become a useful technique for
      clinical applications in the horse-breeding industry. However, both ICSI
      blastocyst and offspring production continues to be limited for most farm and
      wild species. This article reviews technical differences of ICSI performance
      among species, possible biological and methodological reasons for the variable
      efficiency and potential strategies to improve the outcomes. One of the major
      applications of ICSI in animal production is the reproduction of high-value
      specimens. Unfortunately, some domestic species like the bovine show low rates of
      pronuclei formation after sperm injection, which led to the development of
      various artificial activation protocols and sperm pre-treatments that are
      discussed in this article. The impact of ICSI technique on equine breeding
      programs is considered in detail, since in contrast to other species, its use for
      elite horse reproduction has increased in recent years. ICSI has also been used
      to produce genetically modified animals; however, despite numerous attempts in
      several domestic species, only transgenic pigs have been consistently produced.
      Finally, the ICSI is a promising tool for genetic rescue of endangered and wild
      species. In conclusion, while ICSI has become a consistent ART for some species,
      it needs further development for others. The low results obtained for some
      domestic species, the high training needed and the equipment required have
      limited this technique to the production of elite specimens or for research
      purposes.

PMID- 29196495
TI  - Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences
      in NSCLC from African Americans and European Americans.
AB  - Purpose: To determine whether racial differences in gene and miRNA expression
      translates to differences in lung tumor biology with clinical relevance in
      African Americans (AAs) and European Americans (EAs).Experimental Design: The NCI
      Maryland Case Control Study includes seven Baltimore City hospitals and is
      overrepresented with AA patients (~40%). Patients that underwent curative NSCLC
      surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used
      mRNA (n = 22 AAs and 19 EAs) and miRNA (n = 42 AAs and 55 EAs) expression arrays
      to track differences in paired fresh frozen normal tissues and lung tumor
      specimens from AAs and EAs. Pathway enrichment, predicted drug response, tumor
      microenvironment infiltration, cancer immunotherapy antigen profiling, and miRNA
      target enrichment were assessed.Results: AA-enriched differential gene expression
      was characterized by stem cell and invasion pathways. Differential gene
      expression in lung tumors from EAs was primarily characterized by cell
      proliferation pathways. Population-specific gene expression was partly driven by
      population-specific miRNA expression profiles. Drug susceptibility predictions
      revealed a strong inverse correlation between AA resistance and EA sensitivity to
      the same panel of drugs. Statistically significant differences in M1 and M2
      macrophage infiltration were observed in AAs (P < 0.05); however, PD-L1, PD-L2
      expression was similar between both.Conclusions: Comparative transcriptomic
      profiling revealed clear differences in lung tumor biology between AAs and EAs.
      Increased participation by AAs in lung cancer clinical trials are needed to
      integrate, and leverage, transcriptomic differences with other clinical
      information to maximize therapeutic benefit in both AAs and EAs. Clin Cancer Res;
      23(23); 7412-25. (c)2017 AACR.

PMID- 29196496
TI  - Pas de deux: An Intricate Dance of Anther Smut and Its Host.
AB  - The successful interaction between pathogen/parasite and host requires a delicate
      balance between fitness of the former and survival of the latter. To optimize
      fitness a parasite/pathogen must effectively create an environment conducive to
      reproductive success, while simultaneously avoiding or minimizing detrimental
      host defense response. The association between Microbotryum lychnidis-dioicae and
      its host Silene latifolia serves as an excellent model to examine such
      interactions. This fungus is part of a species complex that infects species of
      the Caryophyllaceae, replacing pollen with the fungal spores. In the current
      study, transcriptome analyses of the fungus and its host were conducted during
      discrete stages of bud development so as to identify changes in fungal gene
      expression that lead to spore development and to identify changes associated with
      infection in the host plant. In contrast to early biotrophic phase stages of
      infection for the fungus, the latter stages involve tissue necrosis and in the
      case of infected female flowers, further changes in the developmental program in
      which the ovary aborts and a pseudoanther is produced. Transcriptome analysis via
      Illumina RNA sequencing revealed enrichment of fungal genes encoding small
      secreted proteins, with hallmarks of effectors and genes found to be relatively
      unique to the Microbotryum species complex. Host gene expression analyses also
      identified interesting sets of genes up-regulated, including those involving
      stress response, host defense response, and several agamous-like MADS-box genes
      (AGL61 and AGL80), predicted to interact and be involved in male gametophyte
      development.

PMID- 29196497
TI  - Powerful Inference with the D-Statistic on Low-Coverage Whole-Genome Data.
AB  - The detection of ancient gene flow between human populations is an important
      issue in population genetics. A common tool for detecting ancient admixture
      events is the D-statistic. The D-statistic is based on the hypothesis of a
      genetic relationship that involves four populations, whose correctness is
      assessed by evaluating specific coincidences of alleles between the groups. When
      working with high-throughput sequencing data, calling genotypes accurately is not
      always possible; therefore, the D-statistic currently samples a single base from
      the reads of one individual per population. This implies ignoring much of the
      information in the data, an issue especially striking in the case of ancient
      genomes. We provide a significant improvement to overcome the problems of the D
      statistic by considering all reads from multiple individuals in each population.
      We also apply type-specific error correction to combat the problems of sequencing
      errors, and show a way to correct for introgression from an external population
      that is not part of the supposed genetic relationship, and how this leads to an
      estimate of the admixture rate. We prove that the D-statistic is approximated by
      a standard normal distribution. Furthermore, we show that our method outperforms
      the traditional D-statistic in detecting admixtures. The power gain is most
      pronounced for low and medium sequencing depth (1-10*), and performances are as
      good as with perfectly called genotypes at a sequencing depth of 2*. We show the
      reliability of error correction in scenarios with simulated errors and ancient
      data, and correct for introgression in known scenarios to estimate the admixture
      rates.

PMID- 29196498
TI  - US tobacco companies run court ordered advertisements.

PMID- 29196499
TI  - Nutritional regimens with periodically recurring phases of dietary restriction
      extend lifespan in Drosophila.
AB  - Nutritional interventions such as caloric and dietary restriction increase
      lifespan in various animal models. To identify alternative and less demanding
      nutritional interventions that extend lifespan, we subjected fruit flies (
      Drosophila melanogaster) to weekly nutritional regimens that involved alternating
      a conventional diet with dietary restriction. Short periods of dietary
      restriction (up to 2 d) followed by longer periods of a conventional diet yielded
      minimal increases in lifespan. We found that 3 or more days of contiguous dietary
      restriction (DR) was necessary to yield a lifespan extension similar to that
      observed with persistent DR. Female flies were more responsive to these
      interventions than males. Physiologic changes known to be associated with
      prolonged DR, such as reduced metabolic rates, showed the same time course as
      lifespan extension. Moreover, concurrent transcriptional changes indicative of
      reduced insulin signaling were identified with DR. These physiologic and
      transcriptional changes were sustained, as they were detectable several days
      after switching to conventional diets. Taken together, diets with longer periods
      of DR extended lifespan concurrently with physiologic and transcriptional changes
      that may underlie this increase in lifespan.-Romey-Glusing, R., Li, Y., Hoffmann,
      J., von Frieling, J., Knop, M., Pfefferkorn, R., Bruchhaus, I., Fink, C., Roeder,
      T. Nutritional regimens with periodically recurring phases of dietary restriction
      extend lifespan in Drosophila.

PMID- 29196500
TI  - Reduced prostaglandin I2 signaling in Arid5b-/- primary skeletal muscle cells
      attenuates myogenesis.
AB  - The AT-rich interaction domain (ARID) family of proteins regulates gene
      expression, development, and differentiation. Although Arid5b has important
      functions in adipogenesis and chondrogenesis, the role of Arid5b in skeletal
      muscle myogenesis has not been investigated. Therefore, we isolated primary
      skeletal muscle cells from Arid5b+/+ and Arid5b-/- mice and characterized
      differentiation in these cells. We found that Arid5b-/- primary skeletal muscle
      cells showed differentiation defects and impaired sarcomeric assembly. Microarray
      analysis revealed down-regulation of the prostanoid biosynthesis pathway in
      Arid5b-/- myoblasts, including the genes encoding cyclooxygenase (COX)-1 ( Ptgs1)
      and prostaglandin (PG)I synthase ( Ptgis). Down-regulation of COX-1 and PGI
      synthase was confirmed by real-time PCR and Western blot analyses.
      Correspondingly, the production of PGI2, as measured by ELISA, was reduced in
      Arid5b-/- cells relative to Arid5b+/+ cells. Boyden chamber assays showed that
      migration was increased but chemotaxis was impaired in Arid5b-/- cells. Myoblast
      fusion was also inhibited in Arid5b-/- cells compared with Arid5b+/+ cells.
      Treatment with the PGI2 analog iloprost rescued the defects in myotube formation,
      migration, and fusion. These results demonstrate that Arid5b has a novel and
      essential role in skeletal muscle differentiation by regulating PGI2 production.
      Murray, J., Whitson, R. H., Itakura, K. Reduced prostaglandin I2 signaling in
      Arid5b-/- primary skeletal muscle cells attenuates myogenesis.

PMID- 29196501
TI  - Vitamin D binding protein rs7041 genotype alters vitamin D metabolism in pregnant
      women.
AB  - Research has identified reduced circulating 25-hydroxyvitamin D [25(OH)D] in
      individuals with the rs7041 (c.1296T>G) T allele in the vitamin D binding protein
      gene ( GC); however, the effects of the T allele on vitamin D biomarkers during
      pregnancy and lactation are unknown. Thus, we examined the metabolic effects of
      GC rs7041 on vitamin D biomarkers among third-trimester pregnant ( n = 26),
      lactating ( n = 28), and nonpregnant/nonlactating ( n = 21) women consuming a
      single amount of vitamin D (511 IU/d) and related nutrients for 10-12 wk. T
      allele carriers had less circulating 25(OH)D, regardless of reproductive state
      [thymine-thymine (TT): 80% of guanine-guanine (GG), P = 0.05; guanine-thymine
      (GT): 85% of GG, P = 0.1]. Among pregnant women, the T allele attenuated the
      expected increase in vitamin D binding protein (DBP). Specifically, although GG
      pregnant women exhibited greater DBP (216%, P < 0.0001) than did GG nonpregnant
      women, that difference was lessened among GT women, and TT pregnant women did not
      exhibit greater DBP than TT nonpregnant women. Furthermore, TT pregnant women had
      greater placental 25(OH)D3 to 24,25-dihydroxyvitamin D ratios (251% of GG, P =
      0.07) and less osteocalcin, a bone formation marker, in the cord blood of their
      neonates (24% of GT, P = 0.02). Overall, the GC rs7041 genotype modified the
      effects of pregnancy on maternal and placental vitamin D metabolism, with
      possible functional consequences for fetal bone development and infant health.
      Ganz, A. B., Park, H., Malysheva, O. V., Caudill, M. A. Vitamin D binding protein
      rs7041 genotype alters vitamin D metabolism in pregnant women.

PMID- 29196504
TI  - Considering Family Resources When Making Medical Recommendations.
AB  - Poor families without health insurance present unique challenges for
      pediatricians who want to do what is best for the children who are their
      patients. Families are often willing to make tremendous sacrifices to pay for
      recommended and needed medical care. Physicians may have to decide whether, or
      how strongly to, recommend expensive treatments, especially when any good
      outcomes associated with such treatments are not guaranteed. How should we
      balance the considerations of justice and of the child's best interest with the
      grim realities facing poor families? In this article, we present a case from a
      tertiary care hospital in India in which doctors and parents struggled to figure
      out the best options for a young man with end stage renal disease.

PMID- 29196503
TI  - Sphingolipid regulation of lung epithelial cell mitophagy and necroptosis during
      cigarette smoke exposure.
AB  - The mechanisms by which lung structural cells survive toxic exposures to
      cigarette smoke (CS) are not well defined but may involve proper disposal of
      damaged mitochondria by macro-autophagy (mitophagy), processes that may be
      influenced by pro-apoptotic ceramide (Cer) or its precursor dihydroceramide
      (DHC). Human lung epithelial and endothelial cells exposed to CS exhibited
      mitochondrial damage, signaled by phosphatase and tensin homolog-induced putative
      kinase 1 (PINK1) phosphorylation, autophagy, and necroptosis. Although cells
      responded to CS by rapid inhibition of DHC desaturase, which elevated DHC levels,
      palmitoyl (C16)-Cer also increased in CS-exposed cells. Whereas DHC augmentation
      triggered autophagy without cell death, the exogenous administration of C16-Cer
      was sufficient to trigger necroptosis. Inhibition of Cer-generating acid
      sphingomyelinase reduced both CS-induced PINK1 phosphorylation and necroptosis.
      When exposed to CS, Pink1-deficient ( Pink1-/-) mice, which are protected from
      airspace enlargement compared with wild-type littermates, had blunted C16-Cer
      elevations and less lung necroptosis. CS-exposed Pink1-/- mice also exhibited
      significantly increased levels of lignoceroyl (C24)-DHC, along with increased
      expression of Cer synthase 2 ( CerS2), the enzyme responsible for its production.
      This suggested that a combination of high C24-DHC and low C16-Cer levels might
      protect against CS-induced necroptosis. Indeed, CerS2-/- mice, which lack C24-DHC
      at the expense of increased C16-Cer, were more susceptible to CS, developing
      airspace enlargement following only 1 month of exposure. These results implicate
      DHCs, in particular, C24-DHC, as protective against CS toxicity by enhancing
      autophagy, whereas C16-Cer accumulation contributes to mitochondrial damage and
      PINK1-mediated necroptosis, which may be amplified by the inhibition of C24-DHC
      producing CerS2.-Mizumura, K., Justice, M. J., Schweitzer, K. S., Krishnan, S.,
      Bronova, I., Berdyshev, E. V., Hubbard, W. C., Pewzner-Jung, Y., Futerman, A. H.,
      Choi, A. M. K., Petrache, I. Sphingolipid regulation of lung epithelial cell
      mitophagy and necroptosis during cigarette smoke exposure.

PMID- 29196502
TI  - Identifying the localization and exploring a functional role for Gprc5c in the
      kidney.
AB  - The investigation of orphan GPCRs (GPRs) has the potential to uncover novel
      insights into whole animal physiology. In this study, our goal was to determine
      the renal localization of Gprc5c, a receptor that we previously reported to be
      highly expressed in murine whole kidney, and to examine physiologic parameters in
      Gprc5c knockout (KO) mice to gain insight into function. Gprc5c localized to the
      apical membrane of renal proximal tubules (PTs) in mice, rats, and humans. With
      the comparison of Gprc5c wild-type (WT) and KO mice, we found that Gprc5c KO mice
      have altered acid-base homeostasis. Specifically, Gprc5c KO mice have lower blood
      pH and higher urine pH compared with WT mice, with a reduced level of titratable
      acids in their urine. In an in vitro GPCR internalization assay, we observed that
      Gprc5c internalization (an index of activation) was triggered by alkaline
      extracellular pH. Furthermore, with the use of an in vitro BCECF assay, we
      observed that Gprc5c increases Na+/H+ exchanger 3 (NHE3) activity at alkaline pH.
      We also find that the NHE3 activity is reduced in Gprc5c KO mice by 2 photon
      imaging in seminaphthorhodafluors (SNARF)-4F-loaded kidney sections. NHE3 is a
      primary contributor to apical transport of H+ in the renal PT. Together, these
      data imply that Gprc5c modulates the renal contribution to systemic pH
      homeostasis, at least in part, by taking part in the regulation of NHE3.
      Rajkumar, P., Cha, B., Yin, J., Arend, L. J., Paunescu, T. G., Hirabayashi, Y.,
      Donowitz, M., Pluznick, J. L. Identifying the localization and exploring a
      functional role for Gprc5c in the kidney.

PMID- 29196505
TI  - Trends in Executive Functioning in Extremely Preterm Children Across 3 Birth
      Eras.
AB  - BACKGROUND AND OBJECTIVES: To determine if executive functioning outcomes at
      school age are different for extremely preterm (EP; <28 weeks' gestation) or
      extremely low birth weight (ELBW; <1000 g birth weight) children born in 1991 to
      1992, 1997, and 2005 relative to their term-born peers. METHODS: Population-based
      cohorts of all EP/ELBW survivors born in the state of Victoria, Australia, in
      1991 to 1992, 1997, and 2005, and contemporaneous controls (matched for expected
      date of birth, sex, mother's country of birth [English speaking or not], and
      health insurance status) were recruited at birth. At 7 to 8 years of age, parents
      of 613 children who were EP/ELBW and 564 children who were controls rated their
      children's executive functioning on the Behavior Rating Inventory of Executive
      Function (BRIEF). The proportion of children with elevated BRIEF scores (in the
      clinically significant range) in each birth group and era was compared by using
      logistic regression. Sensitivity analyses explored these associations after
      excluding children with intellectual impairment. RESULTS: Across the eras,
      EP/ELBW children had higher rates of elevated scores than controls in almost all
      BRIEF domains. The 2005 EP/ELBW cohort had increased executive dysfunction
      compared with earlier cohorts, particularly in working memory and planning and
      organization. This effect persisted after accounting for demographic factors and
      weakened slightly when those with intellectual impairment were excluded.
      CONCLUSIONS: These results indicate a concerning trend of increasing executive
      dysfunction for EP/ELBW children who were born more recently. This may have
      adverse implications for other functional domains, such as academic achievement
      and social-emotional well-being.

PMID- 29196506
TI  - A Pediatrician's Day in Immigration Court.

PMID- 29196507
TI  - FcRn is mother's milk to allergen tolerance.
AB  - In this issue Ohsaki et al. (https://doi.org/10.1084/jem.20171163) explain how
      breastfeeding can prevent the onset of food allergies in offspring by instructing
      T reg formation via neonatal Fc receptor (FcRn)-mediated transfer and uptake of
      allergen-containing IgG immune complexes (Ig-ICs) by gut dendritic cells (DCs).

PMID- 29196509
TI  - Postpartum Depression: What Do Pediatricians Need to Know?

PMID- 29196510
TI  - Necrotizing Enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a frequently encountered condition in the
      premature neonate, which can have devastating effects. The signs and symptoms of
      NEC are variable and can be confused with those of sepsis. An abdominal
      radiograph is often obtained for diagnosis, and findings that indicate NEC
      include pneumatosis and portal venous gas. The treatment of NEC includes
      gastrointestinal rest, gastric decompression, broad-spectrum intravenous
      antibiotics, and systemic support. A finding of pneumoperitoneum signifies
      intestinal perforation, which requires surgical intervention. Long-term sequelae
      of NEC include short-gut syndrome, intestinal stricture, and neurodevelopmental
      delays. The presentation of intestinal stricture can be puzzling. It can appear
      at presentation as a bowel obstruction or, conversely, as increased stool output
      or diarrhea. The clinician should have a high level of suspicion for intestinal
      stricture in a patient with a history of NEC.

PMID- 29196511
TI  - Compartment Syndrome in the Pediatric Patient.

PMID- 29196512
TI  - Case 1: Otorrhea, Otalgia, and Blurry Vision in an 11-year-old Girl.

PMID- 29196508
TI  - An integrated computational and experimental study uncovers FUT9 as a metabolic
      driver of colorectal cancer.
AB  - Metabolic alterations play an important role in cancer and yet, few metabolic
      cancer driver genes are known. Here we perform a combined genomic and metabolic
      modeling analysis searching for metabolic drivers of colorectal cancer. Our
      analysis predicts FUT9, which catalyzes the biosynthesis of Ley glycolipids, as a
      driver of advanced-stage colon cancer. Experimental testing reveals FUT9's
      complex dual role; while its knockdown enhances proliferation and migration in
      monolayers, it suppresses colon cancer cells expansion in tumorspheres and
      inhibits tumor development in a mouse xenograft models. These results suggest
      that FUT9's inhibition may attenuate tumor-initiating cells (TICs) that are known
      to dominate tumorspheres and early tumor growth, but promote bulk tumor cells. In
      agreement, we find that FUT9 silencing decreases the expression of the colorectal
      cancer TIC marker CD44 and the level of the OCT4 transcription factor, which is
      known to support cancer stemness. Beyond its current application, this work
      presents a novel genomic and metabolic modeling computational approach that can
      facilitate the systematic discovery of metabolic driver genes in other types of
      cancer.

PMID- 29196513
TI  - Case 2: Progressive Abdominal Pain in a 3-year-old Boy with Repaired Congenital
      Diaphragmatic Hernia.

PMID- 29196514
TI  - Case 3: Increased Snoring in a 7-year-old Boy.

PMID- 29196515
TI  - Case 4: Hemoptysis in a 17-year-old Chinese Boy.

PMID- 29196516
TI  - Case 5: A 13-year-old Boy with Abdominal Pain and Diarrhea.

PMID- 29196517
TI  - Case 6: Head Swelling After Hair Braiding in a 6-year-old Girl.

PMID- 29196518
TI  - The Gifted Child.

PMID- 29196519
TI  - Correction.

PMID- 29196520
TI  - Visual Diagnosis: An 11-year-old Boy with Right Thigh Swelling.

PMID- 29196521
TI  - ERRATUM.

PMID- 29196522
TI  - MotI (DgrA) acts as a molecular clutch on the flagellar stator protein MotA in
      Bacillus subtilis.
AB  - Stator elements consisting of MotA4MotB2 complexes are anchored to the cell wall,
      extend through the cell membrane, and interact with FliG in the cytoplasmic C
      ring rotor of the flagellum. The cytoplasmic loop of MotA undergoes proton-driven
      conformational changes that drive flagellar rotation. Functional regulators
      inhibit motility by either disengaging or jamming the stator-rotor interaction.
      Here we show that the YcgR homolog MotI (formerly DgrA) of Bacillus subtilis
      inhibits motility like a molecular clutch that disengages MotA. MotI-inhibited
      flagella rotated freely by Brownian motion, and suppressor mutations in MotA that
      were immune to MotI inhibition were located two residues downstream of the
      critical force generation site. The 3D structure of MotI bound to c-di-GMP was
      solved, and MotI-fluorescent fusions localized as transient MotA-dependent puncta
      at the membrane when induced at subinhibitory levels. Finally, subinhibitory
      levels of MotI expression resulted in incomplete inhibition and proportional
      decreases in swimming speed. We propose a model in which flagellar stators are
      disengaged and sequestered from the flagellar rotor when bound by MotI.

PMID- 29196523
TI  - DNA replication timing alterations identify common markers between distinct
      progeroid diseases.
AB  - Progeroid syndromes are rare genetic disorders that phenotypically resemble
      natural aging. Different causal mutations have been identified, but no molecular
      alterations have been identified that are in common to these diseases. DNA
      replication timing (RT) is a robust cell type-specific epigenetic feature highly
      conserved in the same cell types from different individuals but altered in
      disease. Here, we characterized DNA RT program alterations in Hutchinson-Gilford
      progeria syndrome (HGPS) and Rothmund-Thomson syndrome (RTS) patients compared
      with natural aging and cellular senescence. Our results identified a progeroid
      specific RT signature that is common to cells from three HGPS and three RTS
      patients and distinguishes them from healthy individuals across a wide range of
      ages. Among the RT abnormalities, we identified the tumor protein p63 gene (TP63)
      as a gene marker for progeroid syndromes. By using the redifferentiation of four
      patient-derived induced pluripotent stem cells as a model for the onset of
      progeroid syndromes, we tracked the progression of RT abnormalities during
      development, revealing altered RT of the TP63 gene as an early event in disease
      progression of both HGPS and RTS. Moreover, the RT abnormalities in progeroid
      patients were associated with altered isoform expression of TP63 Our findings
      demonstrate the value of RT studies to identify biomarkers not detected by other
      methods, reveal abnormal TP63 RT as an early event in progeroid disease
      progression, and suggest TP63 gene regulation as a potential therapeutic target.

PMID- 29196524
TI  - Protein kinase C and calcineurin cooperatively mediate cell survival under
      compressive mechanical stress.
AB  - Cells experience compressive stress while growing in limited space or migrating
      through narrow constrictions. To survive such stress, cells reprogram their
      intracellular organization to acquire appropriate mechanical properties. However,
      the mechanosensors and downstream signaling networks mediating these changes
      remain largely unknown. Here, we have established a microfluidic platform to
      specifically trigger compressive stress, and to quantitatively monitor single
      cell responses of budding yeast in situ. We found that yeast senses compressive
      stress via the cell surface protein Mid2 and the calcium channel proteins Mid1
      and Cch1, which then activate the Pkc1/Mpk1 MAP kinase pathway and calcium
      signaling, respectively. Genetic analysis revealed that these pathways work in
      parallel to mediate cell survival. Mid2 contains a short intracellular tail and a
      serine-threonine-rich extracellular domain with spring-like properties, and both
      domains are required for mechanosignaling. Mid2-dependent spatial activation of
      the Pkc1/Mpk1 pathway depolarizes the actin cytoskeleton in budding or shmooing
      cells, thereby antagonizing polarized growth to protect cells under compressive
      stress conditions. Together, these results identify a conserved signaling network
      responding to compressive mechanical stress, which, in higher eukaryotes, may
      ensure cell survival in confined environments.

PMID- 29196526
TI  - Metabolic activity induces membrane phase separation in endoplasmic reticulum.
AB  - Membrane phase behavior has been well characterized in model membranes in vitro
      under thermodynamic equilibrium state. However, the widely observed differences
      between biological membranes and their in vitro counterparts are placing more
      emphasis on nonequilibrium factors, including influx and efflux of lipid
      molecules. The endoplasmic reticulum (ER) is the largest cellular membrane system
      and also the most metabolically active organelle responsible for lipid synthesis.
      However, how the nonequilibrium metabolic activity modulates ER membrane phase
      has not been investigated. Here, we studied the phase behavior of functional ER
      in the context of lipid metabolism. Utilizing advanced vibrational imaging
      technique, that is, stimulated Raman scattering microscopy, we discovered that
      metabolism of palmitate, a prevalent saturated fatty acid (SFA), could drive
      solid-like domain separation from the presumably uniformly fluidic ER membrane, a
      previously unknown phenomenon. The potential of various fatty acids to induce
      solid phase can be predicted by the transition temperatures of their major
      metabolites. Interplay between saturated and unsaturated fatty acids is also
      observed. Hence, our study sheds light on cellular membrane biophysics by
      underscoring the nonequilibrium metabolic status of living cell.

PMID- 29196529
TI  - No Association of Waist Circumference and Prostate Cancer in the Cancer
      Prevention Study II Nutrition Cohort.
AB  - Background: The relationship between excess body weight and prostate cancer risk
      is unclear. However, some evidence suggests that waist circumference, which
      provides a measure of central adiposity, may be positively associated with more
      advanced stages or grades of prostate cancer.Methods: The association between
      waist circumference and prostate cancer was investigated among 46,094 men
      enrolled in the Cancer Prevention Study II Nutrition Cohort, of whom 5,711 were
      diagnosed with this cancer between 1997 and 2013. Using Cox proportional hazards
      regression, we examined associations of weight circumference with total and high
      grade prostate cancer incidence and with prostate cancer mortality.Results: In
      both categorical and continuous analyses, waist circumference was not associated
      with total or high-grade (Gleason score >= 8) prostate cancer incidence or with
      prostate cancer mortality regardless of whether body mass index was adjusted for
      in the statistical model. Waist circumference was inversely associated with low
      grade (Gleason score < 8) prostate cancer, but the association was not
      statistically significant after adjustment for body mass index.Conclusions: Our
      results suggest that central adiposity, as measured by waist circumference, is
      not significantly associated with prostate cancer incidence or mortality.Impact:
      Compared with men in other studies with significant results, men in our study
      were considerably older, suggesting that age may influence the association
      between waist circumference and prostate cancer. Cancer Epidemiol Biomarkers
      Prev; 26(12); 1812-4. (c)2017 AACR.

PMID- 29196527
TI  - Profile of Joachim Frank, Richard Henderson, and Jacques Dubochet, 2017 Nobel
      Laureates in Chemistry.

PMID- 29196525
TI  - Mapping local and global variability in plant trait distributions.
AB  - Our ability to understand and predict the response of ecosystems to a changing
      environment depends on quantifying vegetation functional diversity. However,
      representing this diversity at the global scale is challenging. Typically, in
      Earth system models, characterization of plant diversity has been limited to
      grouping related species into plant functional types (PFTs), with all trait
      variation in a PFT collapsed into a single mean value that is applied globally.
      Using the largest global plant trait database and state of the art Bayesian
      modeling, we created fine-grained global maps of plant trait distributions that
      can be applied to Earth system models. Focusing on a set of plant traits closely
      coupled to photosynthesis and foliar respiration-specific leaf area (SLA) and dry
      mass-based concentrations of leaf nitrogen ([Formula: see text]) and phosphorus
      ([Formula: see text]), we characterize how traits vary within and among over
      50,000 [Formula: see text]-km cells across the entire vegetated land surface. We
      do this in several ways-without defining the PFT of each grid cell and using 4 or
      14 PFTs; each model's predictions are evaluated against out-of-sample data. This
      endeavor advances prior trait mapping by generating global maps that preserve
      variability across scales by using modern Bayesian spatial statistical modeling
      in combination with a database over three times larger than that in previous
      analyses. Our maps reveal that the most diverse grid cells possess trait
      variability close to the range of global PFT means.

PMID- 29196531
TI  - IAEA and SNMMI Cooperative Agreement.

PMID- 29196530
TI  - From the ABNM: Improvement in Medical Practice.

PMID- 29196532
TI  - SNMMI Leadership Update: Budget and Strategic Plan Alignment for Growth.

PMID- 29196534
TI  - 2017 SNMMI Highlights Lecture: Cardiovascular Nuclear Medicine.

PMID- 29196535
TI  - WNK1 kinase and the termination factor PCF11 connect nuclear mRNA export with
      transcription.
AB  - Nuclear gene transcription is coordinated with transcript release from the
      chromatin template and messenger RNA (mRNA) export to the cytoplasm. Here we
      describe the role of nuclear-localized kinase WNK1 (with no lysine [K] 1) in the
      mammalian mRNA export pathway even though it was previously established as a
      critical regulator of ion homeostasis in the cytoplasm. Our data reveal that WNK1
      phosphorylates the termination factor PCF11 on its RNA polymerase II (Pol II) C
      terminal domain (CTD)-interacting domain (CID). Furthermore, phosphorylation of
      the PCF11 CID weakens its interaction with Pol II. We predict that WNK1 and the
      associated phosphorylation of the PCF11 CID act to promote transcript release
      from chromatin-associated Pol II. This in turn facilitates mRNA export to the
      cytoplasm.

PMID- 29196536
TI  - Novel transcriptional networks regulated by CLOCK in human neurons.
AB  - The molecular mechanisms underlying human brain evolution are not fully
      understood; however, previous work suggested that expression of the transcription
      factor CLOCK in the human cortex might be relevant to human cognition and
      disease. In this study, we investigated this novel transcriptional role for CLOCK
      in human neurons by performing chromatin immunoprecipitation sequencing for
      endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK
      knockdown in differentiated human neurons in vitro. These data suggested that
      CLOCK regulates the expression of genes involved in neuronal migration, and a
      functional assay showed that CLOCK knockdown increased neuronal migratory
      distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of
      genes implicated in neuropsychiatric disorders, and the expression of these
      networks is driven by hub genes with human-specific patterns of expression. These
      data support a role for CLOCK-regulated transcriptional cascades involved in
      human brain evolution and function.

PMID- 29196537
TI  - ESCO1/2's roles in chromosome structure and interphase chromatin organization.
AB  - ESCO1/2 acetyltransferases mediating SMC3 acetylation and sister chromatid
      cohesion (SCC) are differentially required for genome integrity and development.
      Here we established chicken DT40 cell lines with mutations in ESCO1/2, SMC3
      acetylation, and the cohesin remover WAPL. Both ESCO1 and ESCO2 promoted SCC,
      while ESCO2 was additionally and specifically required for proliferation and
      centromere integrity. ESCO1 overexpression fully suppressed the slow
      proliferation and centromeric separation phenotypes of esco2 cells but only
      partly suppressed its chromosome arm SCC defects. Concomitant inactivation of
      ESCO1 and ESCO2 caused lethality owing to compromised mitotic chromosome
      segregation. Neither wapl nor acetyl-mimicking smc3-QQ mutations rescued esco1
      esco2 lethality. Notably, esco1 esco2 wapl conditional mutants showed very severe
      proliferation defects associated with catastrophic mitoses and also abnormal
      interphase chromatin organization patterns. The results indicate that cohesion
      establishment by vertebrate ESCO1/2 is linked to interphase chromatin
      architecture formation, a newly identified function of cohesin acetyltransferases
      that is both fundamentally and medically relevant.

PMID- 29196538
TI  - Parental DNA Methylation States Are Associated with Heterosis in Epigenetic
      Hybrids.
AB  - Despite the importance and wide exploitation of heterosis in commercial crop
      breeding, the molecular mechanisms behind this phenomenon are not completely
      understood. Recent studies have implicated changes in DNA methylation and small
      RNAs in hybrid performance; however, it remains unclear whether epigenetic
      changes are a cause or a consequence of heterosis. Here, we analyze a large panel
      of over 500 Arabidopsis (Arabidopsis thaliana) epigenetic hybrid plants
      (epiHybrids), which we derived from near-isogenic but epigenetically divergent
      parents. This proof-of-principle experimental system allowed us to quantify the
      contribution of parental methylation differences to heterosis. We measured traits
      such as leaf area, growth rate, flowering time, main stem branching, rosette
      branching, and final plant height and observed several strong positive and
      negative heterotic phenotypes among the epiHybrids. Using an epigenetic
      quantitative trait locus mapping approach, we were able to identify specific
      differentially methylated regions in the parental genomes that are associated
      with hybrid performance. Sequencing of methylomes, transcriptomes, and genomes of
      selected parent-epiHybrid combinations further showed that these parental
      differentially methylated regions most likely mediate the remodeling of
      methylation and transcriptional states at specific loci in the hybrids. Taken
      together, our data suggest that locus-specific epigenetic divergence between the
      parental lines can directly or indirectly trigger heterosis in Arabidopsis
      hybrids independent of genetic changes. These results add to a growing body of
      evidence that points to epigenetic factors as one of the key determinants of
      hybrid performance.

PMID- 29196541
TI  - Validation of the grown-ups with congenital heart disease score.
AB  - OBJECTIVES: Adults with congenital heart disease in need of heart surgery
      frequently present with significant comorbidity. Furthermore, additional
      technical difficulties often related to redo operations increase the risk for
      postoperative mortality and morbidity. Hence, next to the type of the procedure,
      additional procedure-dependent and procedure-independent factors have to be
      considered for risk evaluation. The recently proposed grown-ups with congenital
      heart disease (GUCH) mortality and morbidity scores account for these additional
      risk factors. We sought to validate their predictive power in a large population
      operated in a single centre. METHODS: Data of all consecutive patients aged 18
      years or more, who underwent surgery for congenital heart disease between 2005
      and 2016, were collected. Mortality was defined as hospital mortality or
      mortality within 30 days following surgery. Morbidity was defined as occurrence
      of one or more of the following complications: renal failure requiring dialysis,
      neurologic deficit persisting at discharge, atrioventricular block requiring
      permanent pacemaker implantation, mechanical circulatory support, phrenic nerve
      injury and unplanned reoperation. The discriminatory power of the GUCH scores was
      assessed using the area under the receiver operating characteristics curve (c
      index, including 95% CI). RESULTS: Eight hundred and twenty-four operations were
      evaluated. Additional procedure-dependent and procedure-independent factors, as
      defined in the GUCH scores, were present in 165 patients (20.0%) and 544 patients
      (66.0%), respectively. Hospital mortality and morbidity was 3.4% and 10.0%,
      respectively. C-index for GUCH mortality score was 0.809 (0.742-0.877). C-index
      for GUCH morbidity score was 0.676 (0.619-0.734). CONCLUSIONS: We could confirm
      the good predictive power of the GUCH mortality score for postoperative mortality
      in a large population of adults with congenital heart disease.

PMID- 29196539
TI  - Biochemical and Structural Analysis of Substrate Specificity of a Phenylalanine
      Ammonia-Lyase.
AB  - Phenylalanine ammonia-lyase (PAL) is the first enzyme of the general
      phenylpropanoid pathway catalyzing the nonoxidative elimination of ammonia from l
      phenylalanine to give trans-cinnamate. In monocots, PAL also displays tyrosine
      ammonia lyase (TAL) activity, leading to the formation of p-coumaric acid. The
      catalytic mechanism and substrate specificity of a major PAL from sorghum
      (Sorghum bicolor; SbPAL1), a strategic plant for bioenergy production, were
      deduced from crystal structures, molecular docking, site-directed mutagenesis,
      and kinetic and thermodynamic analyses. This first crystal structure of a
      monocotyledonous PAL displayed a unique conformation in its flexible inner loop
      of the 4-methylidene-imidazole-5-one (MIO) domain compared with that of
      dicotyledonous plants. The side chain of histidine-123 in the MIO domain dictated
      the distance between the catalytic MIO prosthetic group created from 189Ala-Ser
      Gly191 residues and the bound l-phenylalanine and l-tyrosine, conferring the
      deamination reaction through either the Friedel-Crafts or E2 reaction mechanism.
      Several recombinant mutant SbPAL1 enzymes were generated via structure-guided
      mutagenesis, one of which, H123F-SbPAL1, has 6.2 times greater PAL activity
      without significant TAL activity. Additional PAL isozymes of sorghum were
      characterized and categorized into three groups. Taken together, this approach
      identified critical residues and explained substrate preferences among PAL
      isozymes in sorghum and other monocots, which can serve as the basis for the
      engineering of plants with enhanced biomass conversion properties, disease
      resistance, or nutritional quality.

PMID- 29196540
TI  - Propensity score matched analysis of partial atrioventricular septal defect
      repair in infancy.
AB  - OBJECTIVE: Partial atrioventricular septal defect (pAVSD) is usually repaired
      between 2 and 4 years of age with excellent results. Repair during infancy has
      been associated with poorer outcomes. However, most infants in reported series
      had heart failure or significant left atrioventricular valve (LAVV)
      regurgitation. The impact of surgery during infancy on outcomes remains unclear.
      METHODS: All children at three institutions who underwent repair of pAVSD from
      1975 to 2015 were included. Infants (aged <1 year) were compared with older
      children in a propensity score matched analysis. Variables used to generate
      propensity scores were: failure to thrive, congestive heart failure, preoperative
      LAVV regurgitation, associated congenital heart disease, sex and the presence of
      trisomy 21. RESULTS: pAVSD repair was performed on 430 children, 17.4% (75/430)
      were infants. Infants (mean age 0.5+/-0.3 years) had higher rates of LAVV
      regurgitation, heart failure and additional cardiac malformations than older
      children (mean age 4.7+/-3.5 years). At 30 years, survival for infants was 82.1%
      (95% CI 70.1% to 89.6%) compared with 95.7% (95% CI 91.3% to 97.9%) in older
      children (P<0.001).Propensity score matching yielded 52 well-matched pairs.
      Survival at 30 years was 87.9% (95% CI 75.0% to 94.4%) for infants compared with
      98.1% (95% CI 87.1% to 99.7%) for older children (P=0.04). There was no
      significant difference in freedom from reoperation between the groups.
      CONCLUSIONS: Despite matching for risk factors, survival after repair of pAVSD
      during infancy is lower than that when repair is performed in older children,
      with no difference in reoperation rates. This suggests that elective repair of
      pAVSD should be deferred until after infancy.

PMID- 29196543
TI  - Fluorodeoxyglucose Positron Emission Tomography for Giant Cell Arteritis.

PMID- 29196544
TI  - Too Little Too Late: Effect of Poor Access to Biologics for Patients with
      Rheumatoid Arthritis.

PMID- 29196542
TI  - Cardiac myosin-binding protein C is a novel marker of myocardial injury and
      fibrosis in aortic stenosis.
AB  - OBJECTIVE: Cardiac myosin-binding protein C (cMyC) is an abundant sarcomeric
      protein and novel highly specific marker of myocardial injury. Myocyte death
      characterises the transition from hypertrophy to replacement myocardial fibrosis
      in advanced aortic stenosis. We hypothesised that serum cMyC concentrations would
      be associated with cardiac structure and outcomes in patients with aortic
      stenosis. METHODS: cMyC was measured in two cohorts in which serum had previously
      been prospectively collected: a mechanism cohort of patients with aortic stenosis
      (n=161) and healthy controls (n=46) who underwent cardiac MRI, and an outcome
      cohort with aortic stenosis (n=104) followed for a median of 11.3 years. RESULTS:
      In the mechanism cohort, cMyC concentration correlated with left ventricular mass
      (adjusted I2=11.0 g/m2 per log unit increase in cMyC, P<0.001), fibrosis volume
      (adjusted I2=8.0 g, P<0.001) and extracellular volume (adjusted I2=1.3%, P=0.01)
      in patients with aortic stenosis but not in controls. In those with late
      gadolinium enhancement (LGE) indicative of myocardial fibrosis, cMyC
      concentrations were higher (32 (21-56) ng/L vs 17 (12-24) ng/L without LGE,
      P<0.001). cMyC was unrelated to coronary calcium scores. Unadjusted Cox
      proportional hazards analysis in the outcome cohort showed greater all-cause
      mortality (HR 1.49 per unit increase in log cMyC, 95% CI 1.11 to 2.01, P=0.009).
      CONCLUSIONS: Serum cMyC concentration is associated with myocardial hypertrophy,
      fibrosis and an increased risk of mortality in aortic stenosis. The
      quantification of serum sarcomeric protein concentrations provides objective
      measures of disease severity and their clinical utility to monitor the
      progression of aortic stenosis merits further study. CLINICAL TRIAL REGISTRATION:
      NCT1755936; Post-results.

PMID- 29196545
TI  - Extensive Ecchymosis due to Rotator Cuff Tear.

PMID- 29196546
TI  - Azathioprine Hypersensitivity Syndrome.

PMID- 29196547
TI  - Comorbidities of Inflammatory Arthropathies in the Art of Diego Velazquez.

PMID- 29196548
TI  - Seroconversion from Anti-Th/To to Anticentromere Antibodies in a Patient with
      Systemic Sclerosis.

PMID- 29196549
TI  - Chloroquine Toxicity Misdiagnosed as Fabry Disease Associated with Systemic Lupus
      Erythematosus and Hashimoto Thyroiditis.

PMID- 29196551
TI  - Cardiovascular Risk Prevention in a Canadian Population of Patients with Giant
      Cell Arteritis.

PMID- 29196550
TI  - Progression of Organ Involvement in Systemic Sclerosis Patients with Persistent
      "Late" Nailfold Capillaroscopic Pattern of Microangiopathy: A Prospective Study.

PMID- 29196552
TI  - Advancing the Development of Patient-reported Outcomes for Adult Myositis at
      OMERACT 2016: An International Delphi Study.

PMID- 29196554
TI  - Negligence claims will "spiral out of control" if government doesn't act, say
      MPs.

PMID- 29196555
TI  - RAL GTPases: Biology and Potential as Therapeutic Targets in Cancer.
AB  - More than a hundred proteins comprise the RAS superfamily of small GTPases. This
      family can be divided into RAS, RHO, RAB, RAN, ARF, and RAD subfamilies, with
      each shown to play distinct roles in human cells in both health and disease. The
      RAS subfamily has a well-established role in human cancer with the three genes,
      HRAS, KRAS, and NRAS being the commonly mutated in tumors. These RAS mutations,
      most often functionally activating, are especially common in pancreatic, lung,
      and colorectal cancers. Efforts to inhibit RAS and related GTPases have produced
      inhibitors targeting the downstream effectors of RAS signaling, including
      inhibitors of the RAF-mitogen-activated protein kinase/extracellular signal
      related kinase (ERK)-ERK kinase pathway and the phosphoinositide-3-kinase-AKT
      mTOR kinase pathway. A third effector arm of RAS signaling, mediated by RAL (RAS
      like) has emerged in recent years as a critical driver of RAS oncogenic signaling
      and has not been targeted until recently. RAL belongs to the RAS branch of the
      RAS superfamily and shares a high structural similarity with RAS. In human cells,
      there are two genes, RALA and RALB, both of which have been shown to play roles
      in the proliferation, survival, and metastasis of a variety of human cancers,
      including lung, colon, pancreatic, prostate, skin, and bladder cancers. In this
      review, we summarize the latest knowledge of RAL in the context of human cancer
      and the recent advancements in the development of cancer therapeutics targeting
      RAL small GTPases.

PMID- 29196559
TI  - Remarkable Evolutionary Plasticity of Centromeric Chromatin.
AB  - Centromeres were familiar to cell biologists in the late 19th century, but for
      most eukaryotes the basis for centromere specification has remained enigmatic.
      Much attention has been focused on the cenH3 (CENP-A) histone variant, which
      forms the foundation of the centromere. To investigate the DNA sequence
      requirements for centromere specification, we applied a variety of epigenomic
      approaches, which have revealed surprising diversity in centromeric chromatin
      properties. Whereas each point centromere of budding yeast is occupied by a
      single precisely positioned tetrameric nucleosome with one cenH3 molecule, the
      "regional" centromeres of fission yeast contain unphased presumably octameric
      nucleosomes with two cenH3s. In Caenorhabditis elegans, kinetochores assemble all
      along the chromosome at sites of cenH3 nucleosomes that resemble budding yeast
      point centromeres, whereas holocentric insects lack cenH3 entirely. The
      "satellite" centromeres of most animals and plants consist of cenH3-containing
      particles that are precisely positioned over homogeneous tandem repeats, but in
      humans, different alpha-satellite subfamilies are occupied by CENP-A nucleosomes
      with very different conformations. We suggest that this extraordinary
      evolutionary diversity of centromeric chromatin architectures can be understood
      in terms of the simplicity of the task of equal chromosome segregation that is
      continually subverted by selfish DNA sequences.

PMID- 29196558
TI  - Microfluidic isoform sequencing shows widespread splicing coordination in the
      human transcriptome.
AB  - Understanding transcriptome complexity is crucial for understanding human biology
      and disease. Technologies such as Synthetic long-read RNA sequencing (SLR-RNA
      seq) delivered 5 million isoforms and allowed assessing splicing coordination.
      Pacific Biosciences and Oxford Nanopore increase throughput also but require high
      input amounts or amplification. Our new droplet-based method, sparse isoform
      sequencing (spISO-seq), sequences 100k-200k partitions of 10-200 molecules at a
      time, enabling analysis of 10-100 million RNA molecules. SpISO-seq requires less
      than 1 ng of input cDNA, limiting or removing the need for prior amplification
      with its associated biases. Adjusting the number of reads devoted to each
      molecule reduces sequencing lanes and cost, with little loss in detection power.
      The increased number of molecules expands our understanding of isoform
      complexity. In addition to confirming our previously published cases of splicing
      coordination (e.g., BIN1), the greater depth reveals many new cases, such as MAPT
      Coordination of internal exons is found to be extensive among protein coding
      genes: 23.5%-59.3% (95% confidence interval) of highly expressed genes with
      distant alternative exons exhibit coordination, showcasing the need for long-read
      transcriptomics. However, coordination is less frequent for noncoding sequences,
      suggesting a larger role of splicing coordination in shaping proteins. Groups of
      genes with coordination are involved in protein-protein interactions with each
      other, raising the possibility that coordination facilitates complex formation
      and/or function. We also find new splicing coordination types, involving initial
      and terminal exons. Our results provide a more comprehensive understanding of the
      human transcriptome and a general, cost-effective method to analyze it.

PMID- 29196557
TI  - SelexGLM differentiates androgen and glucocorticoid receptor DNA-binding
      preference over an extended binding site.
AB  - The DNA-binding interfaces of the androgen (AR) and glucocorticoid (GR) receptors
      are virtually identical, yet these transcription factors share only about a third
      of their genomic binding sites and regulate similarly distinct sets of target
      genes. To address this paradox, we determined the intrinsic specificities of the
      AR and GR DNA-binding domains using a refined version of SELEX-seq. We developed
      an algorithm, SelexGLM, that quantifies binding specificity over a large (31-bp)
      binding site by iteratively fitting a feature-based generalized linear model to
      SELEX probe counts. This analysis revealed that the DNA-binding preferences of AR
      and GR homodimers differ significantly, both within and outside the 15-bp core
      binding site. The relative preference between the two factors can be tuned over a
      wide range by changing the DNA sequence, with AR more sensitive to sequence
      changes than GR. The specificity of AR extends to the regions flanking the core
      15-bp site, where isothermal calorimetry measurements reveal that affinity is
      augmented by enthalpy-driven readout of poly(A) sequences associated with
      narrowed minor groove width. We conclude that the increased specificity of AR is
      correlated with more enthalpy-driven binding than GR. The binding models help
      explain differences in AR and GR genomic binding and provide a biophysical
      rationale for how promiscuous binding by GR allows functional substitution for AR
      in some castration-resistant prostate cancers.

PMID- 29196560
TI  - Spindle-to-Cortex Communication in Cleaving Frog Eggs.
AB  - During cytokinesis, the mitotic spindle communicates with the cell cortex to
      position a cleavage furrow that will cut through the cell in the plane defined by
      the metaphase plate. We investigated the molecular basis of this communication in
      Xenopus laevis eggs, where the signal has to travel ~400 um in ~30 min to reach
      the cortex from the first anaphase spindle. At anaphase onset, huge microtubule
      asters grow out from the poles of the spindle and meet at the plane previously
      defined by the metaphase plate. This disc-shaped boundary plane recruits the
      chromosome passenger complex (CPC) and centralspindlin to antiparallel
      microtubule bundles. It grows out to the cell cortex as the asters expand, where
      it induces the furrow. CPC and centralspindlin were not recruited to boundaries
      between asters from different spindles, suggesting a role of chromatin in
      triggering the CPC-positive state. Recruitment of CPC to aster boundaries was
      reconstituted in an extract system, and we observed that recruitment was
      stimulated by proximity to chromatin. Finally, we discuss models for molecular
      processes involved in initiation and growth of the CPC-positive disc that
      communicates the position of the metaphase plate to the cortex over hundreds of
      micrometers in frog eggs.

PMID- 29196561
TI  - Hierarchical Regulation of Centromeric Cohesion Protection by Meikin and
      Shugoshin during Meiosis I.
AB  - The kinetochore is the key apparatus regulating chromosome segregation.
      Particularly in meiosis, unlike in mitosis, sister kinetochores are captured by
      microtubules emanating from the same spindle pole (mono-orientation), and sister
      chromatid cohesion mediated by cohesin is protected at centromeres in the
      following anaphase. Shugoshin, which localizes to centromeres depending on the
      phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting
      meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore
      factor, Moa1 (meikin), which was initially characterized as a mono-orientation
      factor in fission yeast, also regulates cohesion protection. Moa1, which
      associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase)
      to the kinetochores and phosphorylates Spc7 (KNL1), inducing the persistent
      accumulation of Bub1 at kinetochores. The meiotic Bub1 pool ensures robust Sgo1
      (shugoshin) localization and cohesion protection at centromeres by cooperating
      with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Further,
      molecular genetic analyses reveal a hierarchical regulation of centromeric
      cohesion protection by meikin and shugoshin during meiosis I.

PMID- 29196562
TI  - The Role of Bromodomain and Extraterminal Motif (BET) Proteins in Chromatin
      Structure.
AB  - Bromodomain and extraterminal motif (BET) proteins have been widely investigated
      for their roles in gene regulation and their potential as therapeutic targets in
      cancer. Pharmacologic BET inhibitors target the conserved bromodomain
      acetyllysine interaction and do not distinguish between BRD2, BRD3, and BRD4.
      Thus, comparatively little is known regarding the distinct roles played by
      individual family members, as well as the underlying mechanisms that drive the
      transcriptional effects of BET inhibitors. Here we review studies regarding the
      contributions of BET proteins to genome structure and function, including recent
      work identifying a role for BRD2 as a component of functional and physical
      chromatin domain boundaries. We also discuss directions of future studies aimed
      at providing insights into broader architectural functions of BET proteins and
      their roles in chromatin domain boundary formation.

PMID- 29196566
TI  - Section on Allergy and Immunology.

PMID- 29196563
TI  - Corrigendum: Characterization of the neural stem cell gene regulatory network
      identifies OLIG2 as a multifunctional regulator of self-renewal.

PMID- 29196567
TI  - About This Synopsis Book.

PMID- 29196568
TI  - A Synopsis of the Synopses, 2016 to 2017.

PMID- 29196569
TI  - Stem cells take the stairs.
AB  - Human embryonic stem cells progress through multiple stages in their path to
      neural differentiation, but the steps taken along the way are difficult to
      distinguish, limiting our understanding of this important process. Jing and
      colleagues (2) now report comprehensive analyses of transcriptome dynamics during
      this process that reveal five discrete stages, defined in part by highly
      connected transcription factor networks that link progressive stages.
      Surprisingly, the third stage, which appears to be critical for neural fate
      commitment, depends almost entirely on intracellular signaling.

PMID- 29196570
TI  - Reactivation of mutant p53 and induction of apoptosis in human tumor cells by
      maleimide analogs.

PMID- 29196571
TI  - Large-scale analysis of variation in the insulin-like growth factor family in
      humans reveals rare disease links and common polymorphisms.

PMID- 29196572
TI  - Cdh1, a substrate-recruiting component of anaphase-promoting complex/cyclosome
      (APC/C) ubiquitin E3 ligase, specifically interacts with phosphatase and tensin
      homolog (PTEN) and promotes its removal from chromatin.

PMID- 29196573
TI  - Costs of informal nursing care for patients with neurologic disorders: A
      systematic review.
AB  - OBJECTIVE: To systematically review the economic burden of informal nursing care
      (INC), often called informal care, caused by multiple sclerosis (MS), Parkinson
      disease (PD), and epilepsy, with special attention to disease severity. METHODS:
      We systematically searched MEDLINE, PsycINFO, and NHS Economic Evaluation
      Database for articles on the cost of illness of the diseases specified. Title,
      abstract, and full-text review were conducted in duplicate by 2 researchers. The
      distribution of hours and costs of INC were extracted and used to compare the
      relevance of INC across included diseases and disease severity. RESULTS: Seventy
      one studies were included (44 on MS, 17 on PD, and 10 on epilepsy). Studies on
      epilepsy reported an average of 2.3-54.5 monthly hours of INC per patient. For
      PD, average values of 42.9-145.9 hours and for MS average values of 9.2-249 hours
      per patient per month were found. In line with utilized hours, costs of INC were
      lowest for epilepsy (interquartile range [IQR] 229-1,466 purchasing power parity
      US dollars [PPP-USD]) and similar for MS (IQR 4,454-11,222 PPP-USD) and PD (IQR
      1,440-7,117 PPP-USD). In addition, costs of INC increased with disease severity
      and accounted for 38% of total health care costs in severe MS stages on average.
      CONCLUSIONS: The course of diseases and disease severity matter for the amount of
      INC used by patients. For each of the neurologic disorders, an increase in the
      costs of INC, due to increasing disease severity, considerably contributes to the
      rise in total health care costs.

PMID- 29196574
TI  - Clinical biomarkers differentiate myelitis from vascular and other causes of
      myelopathy.
AB  - OBJECTIVE: To assess the predictive value of the initial clinical and
      paraclinical features in the differentiation of inflammatory myelopathies from
      other causes of myelopathy in patients with initial diagnosis of transverse
      myelitis (TM). METHODS: We analyzed the clinical presentation, spinal cord MRI,
      and CSF features in a cohort of 457 patients referred to a specialized myelopathy
      center with the presumptive diagnosis of TM. After evaluation, the myelopathies
      were classified as inflammatory, ischemic/stroke, arteriovenous
      malformations/fistulas, spondylotic, or other. A multivariable logistic
      regression model was used to determine characteristics associated with the final
      diagnosis and predictors that would improve classification accuracy. RESULTS: Out
      of 457 patients referred as TM, only 247 (54%) were confirmed as inflammatory;
      the remaining 46% were diagnosed as vascular (20%), spondylotic (8%), or other
      myelopathy (18%). Our predictive model identified the temporal profile of symptom
      presentation (hyperacute <6 hours, acute 6-48 hours, subacute 48 hours-21 days,
      chronic >21 days), initial motor examination, and MRI lesion distribution as
      characteristics that improve the correct classification rate of myelopathies from
      67% to 87% (multinomial area under the curve increased from 0.32 to 0.67),
      compared to only considering CSF pleocytosis and MRI gadolinium enhancement. Of
      all predictors, the temporal profile of symptoms contributed the most to the
      increased discriminatory power. CONCLUSIONS: The temporal profile of symptoms
      serves as a clinical biomarker in the differential diagnosis of TM. The
      establishment of a definite diagnosis in TM requires a critical analysis of the
      MRI and CSF characteristics to rule out non-inflammatory causes of myelopathy.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for
      patients presenting with myelopathy, temporal profile of symptoms, initial motor
      examination, and MRI lesion distribution distinguish those with inflammatory
      myelopathies from those with other causes of myelopathy.

PMID- 29196575
TI  - Pitfalls in developing precision medicine for genetic epilepsy.

PMID- 29196576
TI  - Apathy is associated with incident dementia in community-dwelling older people.
AB  - OBJECTIVE: To assess whether apathy and depressive symptoms are independently
      associated with incident dementia during 6-year follow-up in a prospective
      observational population-based cohort study. METHODS: Participants were community
      dwelling older people in the Prevention of Dementia by Intensive Vascular Care
      trial, aged 70-78 years, without dementia at baseline. Apathy and depressive
      symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15).
      Dementia during follow-up was established by clinical diagnosis confirmed by an
      independent outcome adjudication committee. Hazard ratios (HRs) were calculated
      using Cox regression analyses. Given its potentially strong relation with
      incipient dementia, the GDS item referring to memory complaints was assessed
      separately. RESULTS: Dementia occurred in 232/3,427 (6.8%) participants. Apathy
      symptoms were associated with dementia (HR 1.28, 95% confidence interval [CI]
      1.12-1.45; p < 0.001), also after adjustment for age, sex, Mini-Mental State
      Examination score, disability, and history of stroke or cardiovascular disease
      (HR 1.21, 95% CI 1.06-1.40; p = 0.007), and in participants without depressive
      symptoms (HR 1.26, 95% CI 1.06-1.49; p = 0.01). Depressive symptoms were
      associated with dementia (HR 1.12, 95% CI 1.05-1.19), also without apathy
      symptoms (HR 1.16, 95% CI 1.03-1.31; p = 0.015), but not after full adjustment or
      after removing the GDS item on memory complaints. CONCLUSIONS: Apathy and
      depressive symptoms are independently associated with incident dementia in
      community-dwelling older people. Subjective memory complaints may play an
      important role in the association between depressive symptoms and dementia. Our
      findings suggest apathy symptoms may be prodromal to dementia and might be used
      in general practice to identify individuals without cognitive impairment at
      increased risk of dementia.

PMID- 29196577
TI  - Comment: Improving the costing of informal caregiving in neurologic populations.

PMID- 29196578
TI  - Precision therapy for epilepsy due to KCNT1 mutations: A randomized trial of oral
      quinidine.
AB  - OBJECTIVE: To evaluate quinidine as a precision therapy for severe epilepsy due
      to gain of function mutations in the potassium channel gene KCNT1. METHODS: A
      single-center, inpatient, order-randomized, blinded, placebo-controlled,
      crossover trial of oral quinidine included 6 patients with severe autosomal
      dominant nocturnal frontal lobe epilepsy (ADNFLE) due to KCNT1 mutation. Order
      was block randomized and blinded. Four-day treatment blocks were used with a 2
      day washout between. Dose started at 900 mg over 3 divided doses then, in
      subsequent participants, was reduced to 600 mg, then 300 mg. Primary outcome was
      seizure frequency measured on continuous video-EEG in those completing the trial.
      RESULTS: Prolonged QT interval occurred in the first 2 patients at doses of 900
      and 600 mg quinidine per day, respectively, despite serum quinidine levels well
      below the therapeutic range (0.61 and 0.51 MUg/mL, reference range 1.3-5.0
      MUg/mL). Four patients completed treatment with 300 mg/d without adverse events.
      Patients completing the trial had very frequent seizures (mean 14 per day, SD 7,
      median 13, interquartile range 10-18). Seizures per day were nonsignificantly
      increased by quinidine (median 2, 95% confidence interval -1.5 to +5, p = 0.15)
      and no patient had a 50% seizure reduction. CONCLUSION: Quinidine did not show
      efficacy in adults and teenagers with ADNFLE. Dose-limiting cardiac side effects
      were observed even in the presence of low measured serum quinidine levels.
      Although small, this trial suggests use of quinidine in ADNFLE is likely to be
      ineffective coupled with considerable cardiac risks. CLINICAL TRIALS
      REGISTRATION: Australian Therapeutic Goods Administration Clinical Trial Registry
      (trial number 2015/0151). CLASSIFICATION OF EVIDENCE: This study provides Class
      II evidence that for persons with severe epilepsy due to gain of function
      mutations in the potassium channel gene KCNT1, quinidine does not significantly
      reduce seizure frequency.

PMID- 29196580
TI  - Sex disparities in access to caregiving in Parkinson disease.
AB  - OBJECTIVE: To compare access to caregiving between men and women with Parkinson
      disease (PD). METHODS: This was a cross-sectional and longitudinal study among
      participants with PD enrolled in the National Parkinson Foundation Parkinson's
      Outcomes Project from 2009 to 2014 at 21 international sites. The primary outcome
      measures were presence of a caregiver at the baseline visit, caregiver burden as
      measured by the Multidimensional Caregiver Strain Index (MCSI) at baseline, and
      time to first paid caregiver. RESULTS: A total of 7,209 participants (63% men,
      37% women) with PD were evaluated. Men had a mean age of 66.0 (SD 9.8) years, and
      women had a mean age of 66.9 (SD 9.7) years. More men than women had a caregiver
      (88.4% vs 79.4%, p < 0.0001). Caregivers of men reported greater strain than
      those of women (MCSI score 19.9 vs 16.4, p < 0.0001). These differences persisted
      after controlling for age, disease stage, number of comorbidities, cognitive and
      mobility measures, and health-related quality of life. In addition, the odds of
      caregiver accompaniment at baseline visit were lower for women compared to men
      (odds ratio 0.76, 95% confidence interval [CI] 0.67-0.86), and women had a faster
      rate to using a paid caregiver than men (hazard ratio 1.76, 95% CI 1.35-2.28)
      after controlling for potential confounders. CONCLUSIONS: Informal caregiving
      resources are lower for women than men with PD, despite the finding that their
      caregivers report less strain than those of men. In addition, women are more
      likely to use formal, paid caregivers. Strategies to improve access to
      caregiving, particularly for women, are needed.

PMID- 29196579
TI  - Clinical and molecular characterization of KCNT1-related severe early-onset
      epilepsy.
AB  - OBJECTIVE: To characterize the phenotypic spectrum, molecular genetic findings,
      and functional consequences of pathogenic variants in early-onset KCNT1 epilepsy.
      METHODS: We identified a cohort of 31 patients with epilepsy of infancy with
      migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct
      Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole
      exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom
      we identified KCNT1 variants on local diagnostic multiple gene panel testing were
      also included. When possible, we performed homology modeling to predict the
      putative effects of variants on protein structure and function. We undertook
      electrophysiologic assessment of mutant KCNT1 channels in a xenopus oocyte model
      system. RESULTS: We identified pathogenic variants in KCNT1 in 12 patients, 4 of
      which are novel. Most variants occurred de novo. Ten patients had a clinical
      diagnosis of EIMFS, and the other 2 presented with early-onset severe nocturnal
      frontal lobe seizures. Three patients had a trial of quinidine with good clinical
      response in 1 patient. Computational modeling analysis implicates abnormal pore
      function (F346L) and impaired tetramer formation (F502V) as putative disease
      mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with
      significantly increased channel amplitude and variable blockade by quinidine.
      CONCLUSIONS: Gain-of-function KCNT1 pathogenic variants cause a spectrum of
      severe focal epilepsies with onset in early infancy. Currently, genotype
      phenotype correlations are unclear, although clinical outcome is poor for the
      majority of cases. Further elucidation of disease mechanisms may facilitate the
      development of targeted treatments, much needed for this pharmacoresistant
      genetic epilepsy.

PMID- 29196581
TI  - Increased midlife triglycerides predict brain beta-amyloid and tau pathology 20
      years later.
AB  - OBJECTIVE: To evaluate the effect of midlife lipid levels on Alzheimer brain
      pathology 20 years later in cognitively normal elderly individuals. METHODS: This
      is a longitudinal cohort study of 318 cognitively normal individuals with data on
      fasting lipid levels at midlife (mean age 54 years). Presence of beta-amyloid
      (Abeta) and tau pathologies 20 years later (mean age 73 years) were detected by
      quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134),
      Abeta (18F-flutemetamol) PET was also performed. RESULTS: CSF Abeta42 and Abeta
      PET revealed Abeta pathology in approximately 20% of the cognitively healthy
      population and CSF Abeta42/phosphorylated tau (p-tau) ratio indicated both Abeta
      and tau pathology in 16%. Higher levels of triglycerides in midlife were
      independently associated with abnormal CSF Abeta42 (odds ratio [OR] 1.34, 95%
      confidence interval [CI] 1.03-1.75, p = 0.029) and abnormal Abeta42/p-tau ratio
      (OR 1.46, 95% CI 1.10-1.93; p = 0.009) adjusting for age, sex, APOE epsilon4,
      education, and multiple vascular risk factors. Triglycerides were also associated
      with abnormal Abeta PET in multivariable regression models, but the association
      was attenuated in the fully adjusted model. Increased levels of medium and large
      low-density lipoprotein subfractions were significantly associated with abnormal
      Abeta PET and large high-density lipoprotein particles were associated with
      decreased risk of abnormal Abeta PET. CONCLUSIONS: Increased levels of
      triglycerides at midlife predict brain Abeta and tau pathology 20 years later in
      cognitively healthy individuals. Certain lipoprotein subfractions may also be
      risk factors for Abeta pathology. These findings further support an involvement
      of lipids in the very early stages of AD development.

PMID- 29196583
TI  - A Season of Thanks and Hope.

PMID- 29196585
TI  - Feasibility of a Nurse-Managed Pain, Agitation, and Delirium Protocol in the
      Surgical Intensive Care Unit.
AB  - BACKGROUND: Society of Critical Care Medicine guidelines recommend the use of
      pain, agitation, and delirium protocols in the intensive care unit. The
      feasibility of nurse management of such protocols in the surgical intensive care
      unit has not been well assessed. OBJECTIVES: To evaluate the percentage of
      adherent medication interventions for patients assessed by using a pain,
      sedation, and delirium protocol. METHODS: Data on all adult patients admitted to
      a surgical intensive care unit from January 2013 through September 2013 who were
      assessed at least once by using a pain, sedation, and delirium protocol were
      retrospectively reviewed. Protocol adherence was evaluated for interventions
      implemented after a nursing assessment. Patients were further divided into 2
      groups on the basis of adherence, and achievement of pain and sedation goals was
      evaluated between groups. RESULTS: Data on 41 patients were included. Of the 603
      pain assessments, 422 (70.0%) led to an intervention adherent to the protocol. Of
      the 249 sedation assessments, 192 (77.1%) led to an adherent intervention. Among
      patients with 75% or greater adherent pain interventions, all interventions met
      pain goals with significantly less fentanyl than that used in interventions that
      did not meet goals. Despite 75% or greater adherence with interventions for
      sedation assessments, only 8.7% of the interventions met sedation goals.
      CONCLUSIONS: A nurse-managed pain, agitation, and delirium protocol can be
      feasibly implemented in a surgical intensive care unit.

PMID- 29196586
TI  - Implementing a Multicomponent Intervention to Prevent Delirium Among Critically
      Ill Patients.
AB  - BACKGROUND: Delirium is common among the critically ill. Nonpharmacologic
      interventions are reportedly effective in reducing incident delirium, but limited
      data specific to this population exist. OBJECTIVES: To assess the efficacy and
      describe the implementation strategy of a multicomponent intervention to prevent
      delirium in an intensive care unit. METHODS: A before-and-after study was
      conducted in an intensive care unit between May 2014 through August 2015. Adult
      participants were enrolled consecutively, excluding only those who refused to
      participate. Tailored interventions took available evidence into consideration.
      Components included early mobilization, physical therapy, reorientation,
      cognitive stimulation, drug reviews, environmental stimulation, avoidance of
      sensory deprivation, pain control, restraint use avoidance, and family
      participation. Incident delirium was assessed twice daily using the Confusion
      Assessment Method for the Intensive Care Unit. Multivariate logistic regression
      was used to control for confounders. RESULTS: The study included 227 patients
      (54.7% male; mean [SD] age, 63.3 [18.3] years). Our strategy significantly
      reduced delirium (from 38% to 24%; relative risk, 0.62; 95% CI, 0.40-0.94; P =
      .02), an association that remained significant after adjusting for confounders.
      Adherence rates were more than 85% in all intervention domains (except daily
      reorientation) that were overseen by health care providers. CONCLUSIONS: The
      strategy was successful in reducing delirium. Self-removals of invasive
      implements decreased, an observation that has not been previously described. No
      difference in mortality rate was seen, as has been reported in other studies.
      Early participation of the whole team, shared leadership, and the provision of
      concrete tasks were key to the success of this multicomponent intervention.

PMID- 29196587
TI  - Perceptions of Family Members, Nurses, and Physicians on Involving Patients'
      Families in Delirium Prevention.
AB  - BACKGROUND: Delirium occurs in up to 80% of patients admitted to an intensive
      care unit. Nonpharmacologic delirium-prevention strategies, which are commonly
      used by the bedside nurse, have reduced the incidence and duration of delirium in
      patients in the intensive care unit. With increasing demands on the nurse,
      strategies such as including the patient's family in delirium prevention
      activities should be investigated. OBJECTIVE To determine opinions and
      willingness of health care providers to involve patients' families in
      nonpharmacologic delirium-prevention activities in the intensive care unit, and
      of patients' families to be involved. METHODS: Two surveys, one for intensive
      care unit nurses and physicians and one for patients' families, were developed
      and administered. The provider survey focused on current delirium-prevention
      practices and opinions about family involvement. The family survey concentrated
      on barriers and willingness to participate in prevention activities. RESULTS:
      Sixty nurses and 58 physicians completed the survey. Most physicians (93%) and
      all nurses believed families could assist with delirium prevention. Only 50%
      reported speaking with family members about delirium and delirium prevention. The
      family survey was completed by 60 family members; 38% reported a provider spoke
      with them about delirium. Family members reported high levels of comfort in
      participating in delirium-prevention activities. CONCLUSIONS: Health care
      providers and family members are supportive of the latter performing delirium
      prevention activities. Family of patients in the intensive care unit may work
      collaboratively with nurses to reduce the incidence and duration of delirium in
      these patients.

PMID- 29196588
TI  - Understanding Stage II Bidirectional Cavopulmonary Shunts.
AB  - Despite improvements in surgical technique and medical management, single
      ventricle lesions remain one of the most challenging congenital heart anomalies
      to treat, and mortality rates are high. Most infants who have single-ventricle
      palliation undergo a sequence of surgeries to optimize pulmonary and systemic
      blood flow. The first surgery to separate pulmonary and systemic blood flow is
      the bidirectional cavopulmonary shunt. This article describes single-ventricle
      lesions and gives a basic overview of outcomes and strategies to improve
      interstage mortality. Preoperative investigations that evaluate stage II
      candidacy are reviewed along with surgical approaches and postoperative
      physiology. Although mortality rates are low and decreasing in patients with
      bidirectional cavopulmonary shunts, morbidity is still a challenge. Nurses must
      understand the pertinent anatomy and physiology and recognize postoperative
      complications early in order to reduce morbidity. Postoperative complications,
      management, outcomes and nursing care are discussed.

PMID- 29196584
TI  - Family Support During Resuscitation: A Quality Improvement Initiative.
AB  - BACKGROUND: Despite increasing support for family presence during cardiopulmonary
      resuscitation, a review of the literature revealed no published protocols or
      training curricula to guide hospitals in implementing a family support provider
      role. OBJECTIVES: To develop a curriculum and train dedicated resuscitation team
      members whose role is to provide family support during in-hospital resuscitation
      events. METHODS: An interdisciplinary team developed a 4-hour training session
      for the family support staff. The session included an introduction to the
      evidence for family presence during resuscitation and local data on
      resuscitations. The training was composed of 4 sections: (1) clinical aspects of
      resuscitation, (2) integration into the resuscitation team and steps for
      providing family support during resuscitation, (3) responding to families in
      distress, and (4) self-care practices. Before and after the training session, the
      participants completed surveys of self-rated knowledge and attitudes toward
      family presence during resuscitation. RESULTS: Fifty-nine social workers and 8
      spiritual care providers were trained in 2015. There was a significant increase
      in all rated aspects of knowledge of the family support role and self-care
      strategies. CONCLUSION: Through the creation of an interdisciplinary curriculum,
      an institution can effectively train health care providers in a new resuscitation
      team role: the family support provider.

PMID- 29196589
TI  - Using SQUIRE 2.0 as a Guide for Planning Your Quality Improvement Project.
AB  - This article is the third of a 4-part quality improvement resource series for
      critical care nurses interested in implementing system process or performance
      improvement projects. Part 1 defined the differences between research and quality
      improvement. Part 2 discussed how nurses and managers could identify meaningful
      quality improvement projects that will make a real difference in their critical
      care unit while fitting within their time constraints and resources. Part 3 uses
      the recently revised Standards for Quality Improvement Reporting Excellence
      guidelines as a basis for designing, implementing, documenting, and publishing
      quality improvement projects.

PMID- 29196590
TI  - The Power of Mentoring.

PMID- 29196591
TI  - Nasogastric Tube Placement in Critically Ill Pediatric Patients.

PMID- 29196592
TI  - The Impact of Early Identification and a Critical Care-Based Sepsis Response Team
      on Sepsis Outcomes.

PMID- 29196593
TI  - Obtaining Accurate Noninvasive Blood Pressure Measurements in Adults.

PMID- 29196594
TI  - Perceptions of Families of Intensive Care Unit Patients Regarding Involvement in
      Delirium-Prevention Activities: A Qualitative Study.
AB  - BACKGROUND: Nonpharmacologic delirium-prevention strategies are commonly used in
      the intensive care unit by bedside nurses. With up to 80% of intensive care unit
      patients becoming delirious, and lacking treatment options, prevention is key.
      However, with increasing nurse workloads, innovative delirium-prevention
      strategies such as involving the patient's family are needed. OBJECTIVE: To gain
      insight into opinions of patients' families regarding active participation in
      delirium-prevention activities to inform specific recommendations for involving
      patients' families in such activities. METHODS: Purposeful sampling was used.
      Patients' families were contacted to be interviewed about their opinions and
      attitudes on participation in nonpharmacologic delirium prevention activities
      while visiting the intensive care unit. An interview guide was created and used
      to facilitate discussion. Interviews were conducted, transcribed verbatim, and
      coded by 2 independent coders. Themes were identified, defined, and compared
      between independent coders; disagreements were resolved by the study team.
      RESULTS: After 10 interviews were conducted, thematic saturation occurred. Three
      major themes emerged: (1) consistent family presence and participation in care,
      (2) improving ease of interactions between family and patient, and (3) delirium
      education for families. CONCLUSION: Family members want to be involved with care
      and delirium prevention; however, many times they do not know what to do without
      the direction of a health care provider. Family members would benefit from open
      dialogue with the bedside nurse to increase family comfort and involvement in
      care.

PMID- 29196596
TI  - Corrigendum: Methods to Synthesize Large DNA Fragments for a Synthetic Yeast
      Genome.

PMID- 29196595
TI  - Identifying Information Resources for Patients in the Intensive Care Unit and
      Their Families.
AB  - BACKGROUND: Providing information to patients in intensive care units and their
      families is challenging. Patients often are admitted unexpectedly and experience
      stress and uncertainty. One source of stress has been identified as unclear,
      uncoordinated, or inconsistent communication and information. Despite the need
      for information, no centrally located, easily accessible, standardized intensive
      care unit education content exists. OBJECTIVE: To identify educational content
      for patients in the intensive care unit and their families across 4 different
      hospitals, develop a general content database, and organize the general content
      into a framework for education of patients and their families. METHODS:
      Educational content for patients in the intensive care units of 4 participating
      hospitals was collected and a gap analysis was performed. RESULTS: Key content
      format and categories were identified. Educational content was organized into an
      information pathway divided into 3 phases: intensive care unit arrival;
      understanding the intensive care unit and partnering in care; and intensive care
      unit transitions. The gap analysis revealed substantial variation in content
      format and categories. CONCLUSIONS: Structuring a digital learning center using
      different stages of the patient's stay in the intensive care unit and placing
      resources in the context of an information pathway can help coordinate education
      for these patients and their families, and creates a consistent communication
      guide for clinicians as well. The optimal digital format should be considered in
      designing the learning center.

PMID- 29196597
TI  - Testing Serum Batches for Mouse Embryonic Stem Cell Culture.
AB  - The variability in embryonic stem (ES) cell culture is due primarily to serum.
      Serum is typically produced in large batches from many animals. However, samples
      may differ depending on the age and diet of the animals, the country of origin,
      and other factors creating lot-to-lot variations. Some vendors test FBS lots for
      compatibility with ES cell culture. Many laboratories prefer to test serum
      batches themselves to identify the lot giving optimal growth. In this protocol,
      small quantities of specific serum batches are obtained from different suppliers
      and tested for their ability to support ES cells in an undifferentiated state. A
      complete test includes the serum batches' influence on plating efficiency, cell
      morphology, toxicity, and, if possible, their ability to support generation of
      chimeras.

PMID- 29196598
TI  - Preparation of DNA from Embryonic Stem Cells or Other Cultured Cells.
AB  - Characterization of embryonic stem (ES) cell-mediated genome alterations,
      including random insertional transgenesis, gene trapping, gene targeting, and
      site-specific recombinase-mediated changes, is performed mostly at the ES cell
      level, before the introduction of these alterations into a mouse. A detailed
      characterization requires a larger amount of DNA than is required for the initial
      detection of the candidates for the desired alteration. This protocol describes
      the preparation of DNA from a 10-cm tissue culture plate. The cells are
      trypsinized and lysed, and DNA is recovered from the lysate by organic extraction
      followed by ethanol precipitation.

PMID- 29196599
TI  - Detergent Lysis of Tissue Culture Cells for Immunoprecipitation.
AB  - This protocol describes the lysis of tissue culture cells for the solubilization
      of proteins of interest for immunoprecipitation. Upon collection of cells by
      centrifugation and depending on the use of either Tris- or phosphate-based cell
      lysis buffers, cells are rinsed, respectively, in either TBS or PBS before lysis.
      If possible, the pH of the Wash buffer should match that of the Lysis buffer.
      Adherent cells can be directly lysed on the plate. This is particularly useful
      upon lysis encompassing mild nonionic detergents, leaving the cytoskeleton
      intact. Alternatively, adherent cells can be scraped off the plate and directly
      resuspended in Lysis buffer or Wash buffer for transfer to a tube followed by the
      addition of Lysis buffer.

PMID- 29196600
TI  - Detergent Lysis of Animal Tissues for Immunoprecipitation.
AB  - This protocol details protein extraction from mouse tissues for
      immunoprecipitation purposes and has been applied for the performance of large
      scale immunoprecipitations of target proteins from various tissues for the
      identification of associated proteins by mass spectroscopy. The key factors in
      performing a successful immunoprecipitation directly relate to the abundance of
      target protein in a particular tissue type and whether or not the embryonic,
      newborn, or adult mouse-derived tissues contain fibrous and other insoluble
      material. Several tissue types, including lung and liver as well as carcinomas,
      contain significant amounts of fibrous tissue that can interfere with an
      immunoprecipitation.

PMID- 29196601
TI  - Immunoprecipitation.
AB  - This immunoprecipitation protocol details individual steps for the enrichment and
      purification process of specific proteins from a complex cell lysate using an
      antibody bound to a solid matrix. Purified antigen(s) can be eluted by various
      methods, and the resultant protein target can be analyzed and/or identified by
      numerous assays, including the enzyme-linked immunosorbent assay (ELISA), western
      blotting, or mass spectrometry.

PMID- 29196602
TI  - Identification and characterization of a core fucosidase from the bacterium
      Elizabethkingia meningoseptica.
AB  - All reported alpha-l-fucosidases catalyze the removal of nonreducing terminal l
      fucoses from oligosaccharides or their conjugates, while having no capacity to
      hydrolyze core fucoses in glycoproteins directly. Here, we identified an alpha
      fucosidase from the bacterium Elizabethkingia meningoseptica with catalytic
      activity against core alpha-1,3-fucosylated substrates, and we named it core
      fucosidase I (cFase I). Using site-specific mutational analysis, we found that
      three acidic residues (Asp-242, Glu-302, and Glu-315) in the predicted active
      pocket are critical for cFase I activity, with Asp-242 and Glu-315 acting as a
      pair of classic nucleophile and acid/base residues and Glu-302 acting in an as
      yet undefined role. These findings suggest a catalytic mechanism for cFase I that
      is different from known alpha-fucosidase catalytic models. In summary, cFase I
      exhibits glycosidase activity that removes core alpha-1,3-fucoses from
      substrates, suggesting cFase I as a new tool for glycobiology, especially for
      studies of proteins with core fucosylation.

PMID- 29196603
TI  - Effects of chondroitin sulfate proteoglycan 4 (NG2/CSPG4) on soft-tissue sarcoma
      growth depend on tumor developmental stage.
AB  - Sarcomas, and the mesenchymal precursor cells from which they arise, express
      chondroitin sulfate proteoglycan 4 (NG2/CSPG4). However, NG2/CSPG4's function and
      its capacity to serve as a therapeutic target in this tumor type are unknown.
      Here, we used cells from human tumors and a genetically engineered autochthonous
      mouse model of soft-tissue sarcomas (STSs) to determine NG2/CSPG4's role in STS
      initiation and growth. Inhibiting NG2/CSPG4 expression in established murine and
      human STSs decreased tumor volume by almost two-thirds and cell proliferation
      rate by 50%. NG2/CSPG4 antibody immunotherapy in human sarcomas established as
      xenografts in mice similarly decreased tumor volume, and expression of a
      lentivirus blocking NG2/CSPG4 expression inhibited tumor cell proliferation and
      increased the latency of engraftment. Gene profiling showed that Ng2/Cspg4
      deletion altered the expression of genes regulating cell proliferation and
      apoptosis. Surprisingly, Ng2/Cspg4 deletion at the time of tumor initiation
      resulted in larger tumors. Gene expression profiling indicated substantial down
      regulation of insulin-like growth factor binding protein (Igfbp) genes when
      Ng2/Cspg4 is depleted at tumor initiation, but not when Ng2/Cspg4 is depleted
      after tumor initiation. Such differences may have clinical significance, as
      therapeutic targeting of a signaling pathway such as NG2/CSPG4 may have different
      effects on cell behavior with tumor progression. NG2/CSPG4 depletion has
      divergent effects, depending on the developmental stage of sarcoma. In
      established tumors, IGF signaling is active, and NG2 inhibition targets cell
      proliferation and apoptosis.

PMID- 29196604
TI  - CaMKII regulates the depalmitoylation and synaptic removal of the scaffold
      protein AKAP79/150 to mediate structural long-term depression.
AB  - Both long-term potentiation (LTP) and depression (LTD) of excitatory synapse
      strength require the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII)
      and its autonomous activity generated by Thr-286 autophosphorylation.
      Additionally, LTP and LTD are correlated with dendritic spine enlargement and
      shrinkage that are accompanied by the synaptic accumulation or removal,
      respectively, of the AMPA-receptor regulatory scaffold protein A-kinase anchoring
      protein (AKAP) 79/150. We show here that the spine shrinkage associated with LTD
      indeed requires synaptic AKAP79/150 removal, which in turn requires CaMKII
      activity. In contrast to normal CaMKII substrates, the substrate sites within the
      AKAP79/150 N-terminal polybasic membrane-cytoskeletal targeting domain were
      phosphorylated more efficiently by autonomous compared with Ca2+/CaM-stimulated
      CaMKII activity. This unusual regulation was mediated by Ca2+/CaM binding to the
      substrate sites resulting in protection from phosphorylation in the presence of
      Ca2+/CaM, a mechanism that favors phosphorylation by prolonged, weak LTD stimuli
      versus brief, strong LTP stimuli. Phosphorylation by CaMKII inhibited AKAP79/150
      association with F-actin; it also facilitated AKAP79/150 removal from spines but
      was not required for it. By contrast, LTD-induced spine removal of AKAP79/150
      required its depalmitoylation on two Cys residues within the N-terminal targeting
      domain. Notably, such LTD-induced depalmitoylation was also blocked by CaMKII
      inhibition. These results provide a mechanism how CaMKII can indeed mediate not
      only LTP but also LTD through regulated substrate selection; however, in the case
      of AKAP79/150, indirect CaMKII effects on palmitoylation are more important than
      the effects of direct phosphorylation. Additionally, our results provide the
      first direct evidence for a function of the well-described AKAP79/150 trafficking
      in regulating LTD-induced spine shrinkage.

PMID- 29196605
TI  - Isoform-independent and -dependent phosphorylation of microtubule-associated
      protein tau in mouse brain during postnatal development.
AB  - Tau is a microtubule (MT)-associated protein that regulates MT dynamics in the
      axons of neurons. Tau binds to MTs via its C-terminal MT-binding repeats. There
      are two types of tau, those with three (3R) or four (4R) MT-binding repeats; 4R
      tau has a stronger MT-stabilizing activity than 3R tau. The MT-stabilizing
      activity of tau is regulated by phosphorylation. Interestingly, both the isoform
      and phosphorylation change at the time of neuronal circuit formation during
      postnatal development; highly phosphorylated 3R tau is replaced with 4R tau,
      which is less phosphorylated. However, it is not known how the transition of the
      isoforms and phosphorylation are regulated. Here, we addressed this question
      using developing mouse brains. Detailed analysis of developing brains revealed
      that the switch from 3R to 4R tau occurred during postnatal day 9 (P9) to P18
      under the same time course as the conversion of phosphorylation from high to low.
      However, hypothyroidism, which is known to delay brain development, delayed the
      timing of tau dephosphorylation but not the exchange of isoforms, indicating that
      isoform switching and phosphorylation are not necessarily linked. Furthermore, we
      confirmed this finding by using mouse brains that expressed a single isoform of
      human tau. Human tau, either 3R or 4R, reduced phosphorylation levels during
      development even though the isoform did not change. We also found that 3R tau and
      4R tau were phosphorylated differently in vivo even at the same developmental
      days. These results show for the first time that the phosphorylation and isoform
      alteration of tau are regulated differently during mouse development.

PMID- 29196606
TI  - Control of endothelial cell tube formation by Notch ligand intracellular domain
      interactions with activator protein 1 (AP-1).
AB  - Notch signaling is a ubiquitous signal transduction pathway found in most if not
      all metazoan cell types characterized to date. It is indispensable for cell
      differentiation as well as tissue growth, tissue remodeling, and apoptosis.
      Although the canonical Notch signaling pathway is well characterized,
      accumulating evidence points to the existence of multiple, less well-defined
      layers of regulation. In this study, we investigated the function of the
      intracellular domain (ICD) of the Notch ligand Delta-like 4 (DLL4). We provide
      evidence that the DLL4 ICD is required for normal DLL4 subcellular localization.
      We further show that it is cleaved and interacts with the JUN proto-oncogene,
      which forms part of the activator protein 1 (AP-1) transcription factor complex.
      Mechanistically, the DLL4 ICD inhibited JUN binding to DNA and thereby controlled
      the expression of JUN target genes, including DLL4 Our work further demonstrated
      that JUN strongly stimulates endothelial cell tube formation and that DLL4
      constrains this process. These results raise the possibility that Notch/DLL4
      signaling is bidirectional and suggest that the DLL4 ICD could represent a point
      of cross-talk between Notch and receptor tyrosine kinase (RTK) signaling.

PMID- 29196608
TI  - Rhesus monkey TRIM5alpha protein SPRY domain contributes to AP-1 activation.
AB  - TRIM5alpha is an important host restriction factor that could potently block
      retrovirus infection. The SPRY domain of TRIM5alpha mediates post-entry
      restriction by recognition of and binding to the retroviral capsid. Human
      TRIM5alpha also functions as an innate immune sensor to activate AP-1 and NF
      kappaB signaling, which subsequently restrict virus replication. Previous studies
      have shown that the AP-1 and NF-kappaB signaling activation relies on the RING
      motif of TRIM5alpha. In this study, we have demonstrated that the SPRY domain is
      essential for rhesus macaque TRIM5alpha to activate AP-1 but not NF-kappaB
      signaling. The AP-1 activation mainly depends on all of the beta-sheet barrel on
      SPRY structure of TRIM5alpha. Furthermore, the SPRY-mediated auto-ubiquitination
      of TRIM5alpha is required for AP-1 activation. This study reports that rhesus
      macaque TRIM5alpha mainly undergoes Lys27-linked and Met1-linked auto
      polyubiquitination. Finally, we found that the TRIM5alpha signaling function was
      positively correlated with its retroviral restriction activity. This study
      discovered an important role of the SPRY domain in immune signaling and antiviral
      activity and further expanded our knowledge of the antiviral mechanism of
      TRIM5alpha.

PMID- 29196607
TI  - Blue light-excited LOV1 and LOV2 domains cooperatively regulate the kinase
      activity of full-length phototropin2 from Arabidopsis.
AB  - Phototropin2 (phot2) is a blue-light (BL) receptor that regulates BL-dependent
      activities for efficient photosynthesis in plants. phot2 comprises two BL
      receiving light-oxygen-voltage-sensing domains (LOV1 and LOV2) and a kinase
      domain. BL-excited LOV2 is thought to be primarily responsible for the BL
      dependent activation of the kinase. However, the molecular mechanisms by which
      small BL-induced conformational changes in the LOV2 domain are transmitted to the
      kinase remain unclear. Here, we used full-length wild-type and mutant phot2
      proteins from Arabidopsis to study their molecular properties in the dark and
      under BL irradiation. Phosphorylation assays and absorption measurements
      indicated that the LOV1 domain assists the thermal relaxation of BL-excited LOV2
      and vice versa. Using small-angle X-ray scattering and electron microscopy, we
      observed that phot2 forms a dimer and has a rod shape with a maximum length of
      188 A and a radius of gyration of 44 A. Under BL, phot2 displayed large
      conformational changes that bent the rod shape. By superimposing the crystal
      structures of the LOV1 dimer, LOV2, and a homology model of the kinase to the
      observed changes, we inferred that the BL-dependent change consisted of
      positional shifts of both LOV2 and the kinase relative to LOV1. Furthermore,
      phot2 mutants lacking the photocycle in LOV1 or LOV2 still exhibited
      conformational changes under BL, suggesting that LOV1 and LOV2 cooperatively
      contribute to the conformational changes that activate the kinase. These results
      suggest that BL-activated LOV1 contributes to the kinase activity of phot2. We
      discuss the possible intramolecular interactions and signaling mechanisms in
      phot2.

PMID- 29196609
TI  - MicroRNA-based therapeutics in cardiovascular disease: screening and delivery to
      the target.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides, which have
      increasingly been recognized as potent post-transcriptional regulators of gene
      expression. MiRNA targeting is defined by the complementarities between positions
      2-8 of miRNA 5'-end with generally the 3'-untranslated region of target mRNAs
      (messenger RNAs). The capacity of miRNAs to simultaneously inhibit many different
      mRNAs allows for an amplification of biological responses. Hence, miRNAs are
      extremely attractive targets for therapeutic regulation in several diseases,
      including cardiovascular. Novel approaches are emerging to identify the miRNA
      functions in cardiovascular biology processes and to improve miRNA delivery in
      the heart and vasculature. In the present study, we provide an overview of
      current studies of miRNA functions in cardiovascular cells by the use of high
      content screening. We also discuss the challenge to achieve a safe and targeted
      delivery of miRNA therapeutics in cardiovascular cells.

PMID- 29196610
TI  - Single-molecule live-cell imaging of bacterial DNA repair and damage tolerance.
AB  - Genomic DNA is constantly under threat from intracellular and environmental
      factors that damage its chemical structure. Uncorrected DNA damage may impede
      cellular propagation or even result in cell death, making it critical to restore
      genomic integrity. Decades of research have revealed a wide range of mechanisms
      through which repair factors recognize damage and co-ordinate repair processes.
      In recent years, single-molecule live-cell imaging methods have further enriched
      our understanding of how repair factors operate in the crowded intracellular
      environment. The ability to follow individual biochemical events, as they occur
      in live cells, makes single-molecule techniques tremendously powerful to uncover
      the spatial organization and temporal regulation of repair factors during DNA
      repair reactions. In this review, we will cover practical aspects of single
      molecule live-cell imaging and highlight recent advances accomplished by the
      application of these experimental approaches to the study of DNA-repair processes
      in prokaryotes.

PMID- 29196611
TI  - Cell signaling abnormalities in cardiomyopathy caused by lamin A/C gene
      mutations.
AB  - Mutations in the lamin A/C gene (LMNA) encoding intermediate filament proteins
      associated with the inner nuclear membrane cause diseases known as laminopathies.
      Most LMNA mutations cause dilated cardiomyopathy with variable skeletal muscular
      dystrophy. Cell signaling abnormalities have been discovered in hearts of mouse
      models of cardiomyopathy caused by LMNA mutations that contribute to
      pathogenesis. These include abnormally increased signaling by extracellular
      signal-regulated kinase 1 and kinase 2 and other mitogen-activated protein
      kinases, protein kinase B/mammalian target of rapamycin complex 1 and
      transforming growth factor-beta. Preclinical research suggests that specific
      inhibitors of these abnormally activated cell signaling pathways may be useful in
      treating human patients with this disease.

PMID- 29196612
TI  - Homeopathic Treatment of Vitiligo: A Report of Fourteen Cases.
AB  - BACKGROUND Vitiligo, also known as leukoderma, is an autoimmune skin condition
      that results in the loss of melanin pigment. Vitiligo is not a rare condition but
      is difficult to treat and is associated with psychological distress. CASE REPORT
      A series of 14 cases of vitiligo are presented that were treated with
      individualized homeopathic remedies that were based on plant, animal, or mineral
      compounds. There were 13 women and one man in the case series, with a mean age
      29.8 years, and a mean follow-up from treatment of 58 months. The mean time
      between the onset of the appearance of vitiligo and the first consultation at our
      clinic was 96 months. Homeopathic treatment for patients is holistic and was
      performed on an individualized basis as described in this case series.
      Photographic images of the skin are presented before and after treatment.
      CONCLUSIONS In 14 patients with vitiligo treated with individualized homeopathy,
      the best results were achieved in the patients who were treated in the early
      stages of the disease. We believe that homeopathy may be effective in the early
      stages of vitiligo, but large controlled clinical studies are needed in this
      area.

PMID- 29196613
TI  - Protective Effect of Luteolin Against Renal Ischemia/Reperfusion Injury via
      Modulation of Pro-Inflammatory Cytokines, Oxidative Stress and Apoptosis for
      Possible Benefit in Kidney Transplant.
AB  - BACKGROUND The acceptances and long-term outcomes of the renal transplantations
      are seriously jeopardized by inflammatory responses and damage to tissues. The
      present study intended to explicate the pharmacological effect of luteolin (LT)
      in renal ischemia/reperfusion (I/R) injury and the possible mechanism of action
      of LT. MATERIAL AND METHODS The effect of LT on the level of interleukin (IL)
      1beta, IL-6, and tumor necrosis factor (TNF)-alpha in the homogenates of kidney
      tissues of male Swiss albino mice was determined after I/R injury. The effect of
      LT on MDA (malondialdehyde), SOD (superoxide dismutase), CAT (catalase), and
      glutathione were also identified by enzyme assay. In addition, Western blotting
      was used to determine the level of Bcl-2, Bax, and caspase-3 in the presence of
      LT. RESULTS The results showed that LT caused significant reduction in the level
      of TNF-alpha, IL-1beta, and IL-6 compared to the I/R group without LT (p>0.05).
      To further confirm this, the efficacy of LT on the histopathology of I/R injured
      renal tissues was studied. It was found that LT restored cellular viability of
      damaged renal tissue. This observation was further confirmed by TUNEL assay,
      where it was found that LT caused considerable reduction in the population of
      apoptotic cells. LT pretreatment significantly increased Bcl-2 expression and
      reduced the level of Bax expression together with a reduction in the level of
      caspase-3 expression. CONCLUSIONS Luteolin showed its effect by interfering and
      attenuating a number of pathways, including pathways for inflammation and
      apoptosis in renal tissues.

PMID- 29196615
TI  - Expressed fusion gene landscape and its impact in multiple myeloma.
AB  - Multiple myeloma is a plasma cell malignancy characterized by recurrent IgH
      translocations and well described genomic heterogeneity. Although transcriptome
      profiles in multiple myeloma has been described, landscape of expressed fusion
      genes and their clinical impact remains unknown. To provide a comprehensive and
      detailed fusion gene cartography and suggest new mechanisms of tumorigenesis in
      multiple myeloma, we performed RNA sequencing in a cohort of 255 newly diagnosed
      and homogeneously treated multiple myeloma patients with long follow-up. Here, we
      report that patients have on average 5.5 expressed fusion genes. Kappa and lambda
      light chains and IgH genes are main partners in a third of all fusion genes. We
      also identify recurrent fusion genes that significantly impact both progression
      free and overall survival and may act as drivers of the disease. Lastly, we find
      a correlation between the number of fusions, the age of patients and the clinical
      outcome, strongly suggesting that genomic instability drives prognosis of the
      disease.

PMID- 29196616
TI  - 17beta-Estradiol sensitizes ovarian surface epithelium to transformation by
      suppressing Disabled-2 expression.
AB  - Estrogen replacement therapy increases the risk of human ovarian cancer and
      exogenous estradiol accelerates the onset of ovarian cancer in mouse models. This
      study uses primary cultures of mouse ovarian surface epithelium (OSE) to
      demonstrate that one possible mechanism by which estrogen accelerates the
      initiation of ovarian cancer is by up-regulation of microRNA-378 via the ESR1
      pathway to result in the down-regulation of a tumour suppressor called Disabled-2
      (Dab2). Estrogen suppression of Dab2 was reproducible in vivo and across many
      cell types including mouse oviductal epithelium and primary cultures of human
      ovarian cancer cells. Suppression of Dab2 resulted in increased proliferation,
      loss of contact inhibition, morphological dysplasia, and resistance to oncogene
      induced senescence - all factors that can sensitize OSE to transformation. Given
      that DAB2 is highly expressed in healthy human OSE and is absent in the majority
      of ovarian tumours, this study has taken the first steps to provide a mechanistic
      explanation for how estrogen therapy may play a role in the initiation of ovarian
      cancer.

PMID- 29196614
TI  - Genome-wide association study of classical Hodgkin lymphoma identifies key
      regulators of disease susceptibility.
AB  - Several susceptibility loci for classical Hodgkin lymphoma have been reported.
      However, much of the heritable risk is unknown. Here, we perform a meta-analysis
      of two existing genome-wide association studies, a new genome-wide association
      study, and replication totalling 5,314 cases and 16,749 controls. We identify
      risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 * 10
      8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 * 10
      17), 6q23.3 (rs6928977, P = 4.62 * 10-11), 10p14 (rs3781093, P = 9.49 * 10-13),
      13q34 (rs112998813, P = 4.58 * 10-8) and 16p13.13 (rs34972832, P = 2.12 * 10-8).
      Additionally, independent loci within the HLA region are observed for nodular
      sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and
      mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1).
      The new and established risk loci localise to areas of active chromatin and show
      an over-representation of transcription factor binding for determinants of B-cell
      development and immune response.

PMID- 29196617
TI  - Retarding oxidation of copper nanoparticles without electrical isolation and the
      size dependence of work function.
AB  - Copper nanoparticles (CuNPs) are attractive as a low-cost alternative to their
      gold and silver analogues for numerous applications, although their potential has
      hardly been explored due to their higher susceptibility to oxidation in air. Here
      we show the unexpected findings of an investigation into the correlation between
      the air-stability of CuNPs and the structure of the thiolate capping ligand; of
      the eight different ligands screened, those with the shortest alkyl chain, 
      (CH2)2-, and a hydrophilic carboxylic acid end group are found to be the most
      effective at retarding oxidation in air. We also show that CuNPs are not etched
      by thiol solutions as previously reported, and address the important fundamental
      question of how the work function of small supported metal particles scales with
      particle size. Together these findings set the stage for greater utility of CuNPs
      for emerging electronic applications.

PMID- 29196619
TI  - Opposite effects of Activin type 2 receptor ligands on cardiomyocyte
      proliferation during development and repair.
AB  - Zebrafish regenerate damaged myocardial tissue very effectively. Hence, insights
      into the molecular networks underlying zebrafish heart regeneration might help
      develop alternative strategies to restore human cardiac performance. While TGF
      beta signaling has been implicated in zebrafish cardiac regeneration, the role of
      its individual ligands remains unclear. Here, we report the opposing expression
      response during zebrafish heart regeneration of two genes, mstnb and inhbaa,
      which encode TGF-beta family ligands. Using gain-of-function (GOF) and loss-of
      function (LOF) approaches, we show that these ligands mediate inverse effects on
      cardiac regeneration and specifically on cardiomyocyte (CM) proliferation.
      Notably, we find that Inhbaa functions as a CM mitogen and that its
      overexpression leads to accelerated cardiac recovery and scar clearance after
      injury. In contrast, mstnb GOF and inhbaa LOF both lead to unresolved scarring
      after cardiac injury. We further show that Mstnb and Inhbaa inversely control
      Smad2 and Smad3 transcription factor activities through alternate Activin type 2
      receptors.

PMID- 29196618
TI  - The Kalanchoe genome provides insights into convergent evolution and building
      blocks of crassulacean acid metabolism.
AB  - Crassulacean acid metabolism (CAM) is a water-use efficient adaptation of
      photosynthesis that has evolved independently many times in diverse lineages of
      flowering plants. We hypothesize that convergent evolution of protein sequence
      and temporal gene expression underpins the independent emergences of CAM from C3
      photosynthesis. To test this hypothesis, we generate a de novo genome assembly
      and genome-wide transcript expression data for Kalanchoe fedtschenkoi, an
      obligate CAM species within the core eudicots with a relatively small genome
      (~260 Mb). Our comparative analyses identify signatures of convergence in protein
      sequence and re-scheduling of diel transcript expression of genes involved in
      nocturnal CO2 fixation, stomatal movement, heat tolerance, circadian clock, and
      carbohydrate metabolism in K. fedtschenkoi and other CAM species in comparison
      with non-CAM species. These findings provide new insights into molecular
      convergence and building blocks of CAM and will facilitate CAM-into-C3
      photosynthesis engineering to enhance water-use efficiency in crops.

PMID- 29196620
TI  - Emphatic visualization of sphingomyelin-rich domains by inter-lipid FRET imaging
      using fluorescent sphingomyelins.
AB  - Imaging the distribution of sphingomyelin (SM) in membranes is an important issue
      in lipid-raft research. Recently we developed novel fluorescent SM analogs that
      exhibit partition and dynamic behaviors similar to native SM, and succeeded in
      visualizing lateral domain-segregation between SM-rich liquid-ordered (Lo) and SM
      poor liquid-disordered (Ld) domains. However, because the fluorescent contrast
      between these two domains depends directly on their partition ratio for the
      fluorescent SMs, domain-separation becomes indeterminate when the distribution
      difference is not great enough. In this study, we propose the use of inter-lipid
      Forster resonance energy transfer (FRET) imaging between fluorescent SMs to
      enhance the contrast of the two domains in cases in which the inter-domain
      difference in SM distribution is inadequate for conventional monochromic imaging.
      Our results demonstrate that inter-lipid FRET intensity was significantly higher
      in the Lo domain than in the Ld domain, resulting in a clear and distinguishable
      contrast between the two domains even in poorly phase-separated giant unilamellar
      vesicles. In addition, we show that inter-lipid FRET imaging is useful for
      selective visualization of highly condensed assemblies and/or clusters of SM
      molecules in living cell membranes. Thus, the inter-lipid FRET imaging technique
      can selectively emphasize the SM-condensed domains in both artificial and
      biological membranes.

PMID- 29196622
TI  - Intracellular biomass flocculation as a key mechanism of rapid bacterial killing
      by cationic, amphipathic antimicrobial peptides and peptoids.
AB  - Many organisms rely on antimicrobial peptides (AMPs) as a first line of defense
      against pathogens. In general, most AMPs are thought to kill bacteria by binding
      to and disrupting cell membranes. However, certain AMPs instead appear to inhibit
      biomacromolecule synthesis, while causing less membrane damage. Despite an
      unclear understanding of mechanism(s), there is considerable interest in
      mimicking AMPs with stable, synthetic molecules. Antimicrobial N-substituted
      glycine (peptoid) oligomers ("ampetoids") are structural, functional and
      mechanistic analogs of helical, cationic AMPs, which offer broad-spectrum
      antibacterial activity and better therapeutic potential than peptides. Here, we
      show through quantitative studies of membrane permeabilization, electron
      microscopy, and soft X-ray tomography that both AMPs and ampetoids trigger
      extensive and rapid non-specific aggregation of intracellular biomacromolecules
      that correlates with microbial death. We present data demonstrating that
      ampetoids are "fast killers", which rapidly aggregate bacterial ribosomes in
      vitro and in vivo. We suggest intracellular biomass flocculation is a key
      mechanism of killing for cationic, amphipathic AMPs, which may explain why most
      AMPs require micromolar concentrations for activity, show significant selectivity
      for killing bacteria over mammalian cells, and finally, why development of
      resistance to AMPs is less prevalent than developed resistance to conventional
      antibiotics.

PMID- 29196623
TI  - Evolving autonomous learning in cognitive networks.
AB  - There are two common approaches for optimizing the performance of a machine:
      genetic algorithms and machine learning. A genetic algorithm is applied over many
      generations whereas machine learning works by applying feedback until the system
      meets a performance threshold. These methods have been previously combined,
      particularly in artificial neural networks using an external objective feedback
      mechanism. We adapt this approach to Markov Brains, which are evolvable networks
      of probabilistic and deterministic logic gates. Prior to this work MB could only
      adapt from one generation to the other, so we introduce feedback gates which
      augment their ability to learn during their lifetime. We show that Markov Brains
      can incorporate these feedback gates in such a way that they do not rely on an
      external objective feedback signal, but instead can generate internal feedback
      that is then used to learn. This results in a more biologically accurate model of
      the evolution of learning, which will enable us to study the interplay between
      evolution and learning and could be another step towards autonomously learning
      machines.

PMID- 29196621
TI  - Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells
      to maintain homeostasis.
AB  - Inflammasomes are involved in gut homeostasis and inflammatory pathologies, but
      the role of NLRP3 inflammasome in these processes is not well understood.
      Cryopyrin-associated periodic syndrome (CAPS) patients with NLRP3 mutations have
      autoinflammation in skin, joints, and eyes, but not in the intestine. Here we
      show that the intestines of CAPS model mice carrying an Nlrp3 R258W mutation
      maintain homeostasis in the gut. Additionally, such mice are strongly resistant
      to experimental colitis and colorectal cancer; this is mainly through a
      remodelled gut microbiota with enhanced anti-inflammatory capacity due to
      increased induction of regulatory T cells (Tregs). Mechanistically, NLRP3R258W
      functions exclusively in the lamina propria mononuclear phagocytes to directly
      enhance IL-1beta but not IL-18 secretion. Increased IL-1beta boosts local
      antimicrobial peptides to facilitate microbiota remodelling. Our data show that
      NLRP3R258W-induced remodelling of the gut microbiota, induces local Tregs to
      maintain homeostasis and compensate for otherwise-detrimental intestinal
      inflammation.

PMID- 29196625
TI  - Territory holders and non-territory holders in Ayu fish coexist only in the
      population growth process due to hysteresis.
AB  - Ayu fish form feeding territories during a non-breeding (growing) season. When
      the density of the fish increases, phases gradually change. In the early growing
      season, all fish can hold territories at low density. Once all territory sites
      are occupied, newcomers become floaters. As the density further increases,
      territory holders have to spend much more time in defending their own territory
      and lose the time to feed on algae. Eventually, all fish give up their own
      territories and then form a school. In contrast, when the density decreases,
      territories are directly reformed from the school. In short, ayu fish exhibit a
      different transition, called hysteresis, where the two transitions occur widely
      apart from each other. The dynamics of this intrinsic phenomena has not been
      demonstrated in previous studies. We develop a rate equation to describe the
      population dynamics within territorial competition. Our model successfully
      reproduces territorial hysteresis and indicates that territory holders and
      floaters can coexist only in the process of population growth. Moreover, we also
      find that the two critical densities of territorial hysteresis are conspicuously
      different from each other when the increase of the density of floaters sharply
      influences (step-function-like) the territories.

PMID- 29196624
TI  - RNA-seq of serial kidney biopsies obtained during progression of chronic kidney
      disease from dogs with X-linked hereditary nephropathy.
AB  - Dogs with X-linked hereditary nephropathy (XLHN) have a glomerular basement
      membrane defect that leads to progressive juvenile-onset renal failure. Their
      disease is analogous to Alport syndrome in humans, and they also serve as a good
      model of progressive chronic kidney disease (CKD). However, the gene expression
      profile that affects progression in this disease has only been partially
      characterized. To help fill this gap, we used RNA sequencing to identify
      differentially expressed genes (DEGs), over-represented pathways, and upstream
      regulators that contribute to kidney disease progression. Total RNA from kidney
      biopsies was isolated at 3 clinical time points from 3 males with rapidly
      progressing CKD, 3 males with slowly-progressing CKD, and 2 age-matched controls.
      We identified 70 DEGs by comparing rapid and slow groups at specific time points.
      Based on time course analysis, 1,947 DEGs were identified over the 3 time points
      revealing upregulation of inflammatory pathways: integrin signaling, T cell
      activation, and chemokine and cytokine signaling pathways. T cell infiltration
      was verified by immunohistochemistry. TGF-beta1 was identified as the primary
      upstream regulator. These results provide new insights into the underlying
      molecular mechanisms of disease progression in XLHN, and the identified DEGs can
      be potential biomarkers and therapeutic targets translatable to all CKDs.

PMID- 29196626
TI  - Identification of Borrelia protein candidates in mouse skin for potential
      diagnosis of disseminated Lyme borreliosis.
AB  - In vector-borne diseases, the skin plays an essential role in the transmission of
      vector-borne pathogens between the vertebrate host and blood-feeding arthropods
      and in pathogen persistence. Borrelia burgdorferi sensu lato is a tick-borne
      bacterium that causes Lyme borreliosis (LB) in humans. This pathogen may
      establish a long-lasting infection in its natural vertebrate host where it can
      persist in the skin and some other organs. Using a mouse model, we demonstrate
      that Borrelia targets the skin regardless of the route of inoculation, and can
      persist there at low densities that are difficult to detect via qPCR, but that
      were infective for blood-feeding ticks. Application of immunosuppressive
      dermocorticoids at 40 days post-infection (PI) significantly enhanced the
      Borrelia population size in the mouse skin. We used non-targeted (Ge-LC-MS/MS)
      and targeted (SRM-MS) proteomics to detect several Borrelia-specific proteins in
      the mouse skin at 40 days PI. Detected Borrelia proteins included flagellin, VlsE
      and GAPDH. An important problem in LB is the lack of diagnosis methods capable of
      detecting active infection in humans suffering from disseminated LB. The
      identification of Borrelia proteins in skin biopsies may provide new approaches
      for assessing active infection in disseminated manifestations.

PMID- 29196627
TI  - Pathologic N0 Status in Clinical T1N0M0 Lung Adenocarcinoma is Predictable by the
      Solid Component Proportion with Quantitative CT Number Analysis.
AB  - Correctly predicting pathologic regional node-negative (pN0) disease in patients
      with lung cancer before operation may avoid unnecessary mediastinal lymph node
      dissection (MLND). In this study, we analyze the value of the radiographic and
      histopathological features of primary tumors for predicting pN0 status in cT1N0M0
      lung adenocarcinoma and to establish an optimal surgical strategy for avoiding
      MLND in cT1N0M0 lung adenocarcinoma patients. We retrospectively investigated the
      histopathological and radiographic data of 348 surgically resected cT1N0M0 lung
      adenocarcinoma patients with systematic lymph node dissection from January 2005
      to December 2012. Histopathological features and radiographic features were
      analyzed. Multivariable analysis was used to identify significant predictors of
      pN0 disease. Our results showed that pN0 disease was detected in 306 patients
      (87.9%) among the 348 patients with cT1N0M0 lung adenocarcinoma. A decreasing
      trend of the pN0 disease proportion was observed with both increasing
      histological grade and decreased differentiation (P < 0.001). In multivariable
      analysis, the solid component proportion was a significant predictor of pN0
      disease. Among 110 patients with a solid component proportion of no more than
      21.3%, mediastinal lymph node involvement was not observed. Patients who meet
      this criterion may be successfully managed with lung resection without MLND.

PMID- 29196628
TI  - Multi-physics interactions drive VEGFR2 relocation on endothelial cells.
AB  - Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is a pro-angiogenic
      receptor, expressed on endothelial cells (ECs). Although biochemical pathways
      that follow the VEGFR2 activation are well established, knowledge about the
      dynamics of receptors on the plasma membrane remains limited. Ligand stimulation
      induces the polarization of ECs and the relocation of VEGFR2, either in cell
      protrusions or in the basal aspect in cells plated on ligand-enriched
      extracellular matrix (ECM). We develop a mathematical model in order to simulate
      the relocation of VEGFR2 on the cell membrane during the mechanical adhesion of
      cells onto a ligand-enriched substrate. Co-designing the in vitro experiments
      with the simulations allows identifying three phases of the receptor dynamics,
      which are controlled respectively by the high chemical reaction rate, by the
      mechanical deformation rate, and by the diffusion of free receptors on the
      membrane. The identification of the laws that regulate receptor polarization
      opens new perspectives toward developing innovative anti-angiogenic strategies
      through the modulation of EC activation.

PMID- 29196629
TI  - Immune and Imaging Correlates of Mild Cognitive Impairment Conversion to
      Alzheimer's Disease.
AB  - Amnestic mild cognitive impairment (aMCI) conversion to Alzheimer's disease (AD)
      is seen in a sizable portion of aMCI patients; correlates predicting such
      conversion are poorly defined but neuroinflammation and the reactivation of
      chronic viral infections are suspected to play a role in this phenomenon. We
      analyzed these aspects in two homogeneous groups of aMCI who did or did not
      convert to AD over a 24-months period. Results showed that at baseline in those
      aMCI individuals who did not convert to AD: 1) Abeta1-42 stimulated production of
      the pro-inflammatory cytokines IL6 and IL1beta by CD14+ cells was significantly
      reduced (p = 0.01), 2) CD14+/IL-33+ cells were increased (p = 0.0004); 3) MFI of
      TLR8 and TLR9 was significantly increased, and 4) better preserved hippocampus
      volumes were observed and correlated with IL33+/CD14+ cells. Notably, Abeta1-42
      stimulated production of the antiviral cytokine IFN-lambda was increased as well
      in non-AD converters, although with a borderline statistical significance (p =
      0.05). Data herein indicating that proinflammatory cytokines are reduced, whereas
      IFN-lambda production and TLR8 and 9 MFI are augmented in those aMCI in whom AD
      conversion is not observed suggest that the ability to mount stronger antiviral
      response within an antiiflammatory milieu associates with lack of AD conversion.

PMID- 29196630
TI  - An engineered opsin monomer scrambles phospholipids.
AB  - The G protein-coupled receptor opsin is a phospholipid scramblase that
      facilitates rapid transbilayer phospholipid exchange in liposomes. The mechanism
      by which opsin scrambles lipids is unknown. It has been proposed that lipid
      translocation may occur at protein-protein interfaces of opsin dimers. To test
      this possibility, we rationally engineered QUAD opsin by tryptophan substitution
      of four lipid-facing residues in transmembrane helix 4 (TM4) that is known to be
      important for dimerization. Atomistic molecular dynamics simulations of wild type
      and QUAD opsins combined with continuum modeling revealed that the tryptophan
      substitutions lower the energetically unfavorable residual hydrophobic mismatch
      between TM4 and the membrane, reducing the drive of QUAD opsin to dimerize. We
      purified thermostable wild type and QUAD opsins, with or without a SNAP tag for
      fluorescence labeling. Single molecule fluorescence measurements of purified SNAP
      tagged constructs revealed that both proteins are monomers. Fluorescence-based
      activity assays indicated that QUAD opsin is a fully functional scramblase.
      However, unlike wild type opsin which dimerizes en route to insertion into
      phospholipid vesicles, QUAD opsin reconstitutes as a monomer. We conclude that an
      engineered opsin monomer can scramble phospholipids, and that the lipid-exposed
      face of TM4 is unlikely to contribute to transbilayer phospholipid exchange.

PMID- 29196631
TI  - Conservation of folding and association within a family of spidroin N-terminal
      domains.
AB  - Web spiders synthesize silk fibres, nature's toughest biomaterial, through the
      controlled assembly of fibroin proteins, so-called spidroins. The highly
      conserved spidroin N-terminal domain (NTD) is a pH-driven self-assembly device
      that connects spidroins to super-molecules in fibres. The degree to which forces
      of self-assembly is conserved across spider glands and species is currently
      unknown because quantitative measures are missing. Here, we report the
      comparative investigation of spidroin NTDs originating from the major ampullate
      glands of the spider species Euprosthenops australis, Nephila clavipes,
      Latrodectus hesperus, and Latrodectus geometricus. We characterized equilibrium
      thermodynamics and kinetics of folding and self-association using dynamic light
      scattering, stopped-flow fluorescence and circular dichroism spectroscopy in
      combination with thermal and chemical denaturation experiments. We found
      cooperative two-state folding on a sub-millisecond time scale through a late
      transition state of all four domains. Stability was compromised by repulsive
      electrostatic forces originating from clustering of point charges on the NTD
      surface required for function. pH-driven dimerization proceeded with
      characteristic fast kinetics yielding high affinities. Results showed that
      energetics and kinetics of NTD self-assembly are highly conserved across spider
      species despite the different silk mechanical properties and web geometries they
      produce.

PMID- 29196632
TI  - Automated VSS-based Burn Scar Assessment using Combined Texture and Color
      Features of Digital Images in Error-Correcting Output Coding.
AB  - Assessment of burn scars is an important study in both medical research and
      clinical settings because it can help determine response to burn treatment and
      plan optimal surgical procedures. Scar rating has been performed using both
      subjective observations and objective measuring devices. However, there is still
      a lack of consensus with respect to the accuracy, reproducibility, and
      feasibility of the current methods. Computerized scar assessment appears to have
      potential for meeting such requirements but has been rarely found in literature.
      In this paper an image analysis and pattern classification approach for
      automating burn scar rating based on the Vancouver Scar Scale (VSS) was
      developed. Using the image data of pediatric patients, a rating accuracy of 85%
      was obtained, while 92% and 98% were achieved for the tolerances of one VSS score
      and two VSS scores, respectively. The experimental results suggest that the
      proposed approach is very promising as a tool for clinical burn scar assessment
      that is reproducible and cost-effective.

PMID- 29196633
TI  - Lysophosphatidylcholine acyltransferase 4 is involved in chondrogenic
      differentiation of ATDC5 cells.
AB  - Glycerophospholipids have important structural and functional roles in cells and
      are the main components of cellular membranes. Glycerophospholipids are formed
      via the de novo pathway (Kennedy pathway) and are subsequently matured in the
      remodeling pathway (Lands' cycle). Lands' cycle consists of two steps:
      deacylation of phospholipids by phospholipases A2 and reacylation of
      lysophospholipids by lysophospholipid acyltransferases (LPLATs). LPLATs play key
      roles in the maturation and maintenance of the fatty acid composition of
      biomembranes, and cell differentiation. We examined whether LPLATs are involved
      in chondrogenic differentiation of ATDC5 cells, which can differentiate into
      chondrocytes. Lysophosphatidylcholine acyltransferase 4 (LPCAT4) mRNA expression
      and LPCAT enzymatic activity towards 18:1-, 18:2-, 20:4-, and 22:6-CoA increased
      in the late stage of chondrogenic differentiation, when mineralization occurred.
      LPCAT4 knockdown decreased mRNA and protein levels of chondrogenic markers as
      well as Alcian blue staining intensity and alkaline phosphatase activity in ATDC5
      cells. These results suggest that LPCAT4 plays important roles during the
      transition of chondrocytes into hypertrophic chondrocytes and/or a mineralized
      phenotype.

PMID- 29196634
TI  - Rational engineering of a native hyperthermostable lactonase into a broad
      spectrum phosphotriesterase.
AB  - The redesign of enzyme active sites to alter their function or specificity is a
      difficult yet appealing challenge. Here we used a structure-based design approach
      to engineer the lactonase SsoPox from Sulfolobus solfataricus into a
      phosphotriesterase. The five best variants were characterized and their structure
      was solved. The most active variant, alphasD6 (V27A-Y97W-L228M-W263M)
      demonstrates a large increase in catalytic efficiencies over the wild-type
      enzyme, with increases of 2,210-fold, 163-fold, 58-fold, 16-fold against methyl
      parathion, malathion, ethyl-paraoxon, and methyl-paraoxon, respectively.
      Interestingly, the best mutants are also capable of degrading fensulfothion,
      which is reported to be an inhibitor for the wild-type enzyme, as well as others
      that are not substrates of the starting template or previously reported W263
      mutants. The broad specificity of these engineered variants makes them promising
      candidates for the bioremediation of organophosphorus compounds. Analysis of
      their structures reveals that the increase in activity mainly occurs through the
      destabilization of the active site loop involved in substrate binding, and it has
      been observed that the level of disorder correlates with the width of the enzyme
      specificity spectrum. This finding supports the idea that active site
      conformational flexibility is essential to the acquisition of broader substrate
      specificity.

PMID- 29196635
TI  - MALE STERILE6021 (MS6021) is required for the development of anther cuticle and
      pollen exine in maize.
AB  - The anther cuticle and pollen wall function as physical barriers that protect
      genetic material from various environmental stresses. The anther cuticle is
      composed of wax and cutin, the pollen wall includes exine and intine, and the
      components of the outer exine are collectively called sporopollenin. Other than
      cuticle wax, cutin and sporopollenin are biopolymers compounds. The precise
      constituents and developmental mechanism of these biopolymeric are poorly
      understood. Here, we reported a complete male sterile mutant, male sterile6021,
      in maize. The mutant displayed a smooth anther surface and irregular pollen wall
      formation before anthesis, and its tapetum was degraded immaturely. Gas
      chromatography-mass spectrometry analysis revealed a severe reduction of lipid
      derivatives in the mutant anther. We cloned the gene by map based cloning. It
      encoded a fatty acyl carrier protein reductase that was localized in plastids.
      Expression analysis indicated that MS6021 was mainly expressed in the tapetum and
      microspore after the microspore was released from the tetrad. Functional
      complementation of the orthologous Arabidopsis mutant demonstrated that MS6021 is
      conserved between monocots and dicots and potentially even in flowering plants.
      MS6021 plays a conserved, essential role in the successful development of anther
      cuticle and pollen exine in maize.

PMID- 29196636
TI  - Modeling of the jasmonate signaling pathway in Arabidopsis thaliana with respect
      to pathophysiology of Alternaria blight in Brassica.
AB  - The productivity of Oilseed Brassica, one of the economically important crops of
      India, is seriously affected by the disease, Alternaria blight. The disease is
      mainly caused by two major necrotrophic fungi, Alternaria brassicae and
      Alternaria brassicicola which are responsible for significant yield losses. Till
      date, no resistant source is available against Alternaria blight, hence plant
      breeding methods can not be used to develop disease resistant varieties.
      Jasmonate mediated signalling pathway, which is known to play crucial role during
      defense response against necrotrophs, could be strengthened in Brassica plants to
      combat the disease. Since scanty information is available in Brassica-Alternaria
      pathosystems at molecular level therefore, in the present study efforts have been
      made to model jasmonic acid pathway in Arabidopsis thaliana to simulate the
      dynamic behaviour of molecular species in the model. Besides, the developed model
      was also analyzed topologically for investigation of the hubs node. COI1 is
      identified as one of the promising candidate genes in response to Alternaria and
      other linked components of plant defense mechanisms against the pathogens. The
      findings from present study are therefore informative for understanding the
      molecular basis of pathophysiology and rational management of Alternaria blight
      for securing food and nutritional security.

PMID- 29196637
TI  - Influence of the electrolyte's pH on the properties of electrochemically
      deposited hydroxyapatite coating on additively manufactured Ti64 alloy.
AB  - Properties of the hydroxyapatite obtained by electrochemical assisted deposition
      (ED) are dependent on several factors including deposition temperature,
      electrolyte pH and concentrations, applied potential. All of these factors
      directly influence the morphology, stoichiometry, crystallinity, electrochemical
      behaviour, and particularly the coating thickness. Coating structure together
      with surface micro- and nano-scale topography significantly influence early
      stages of the implant bio-integration. The aim of this study is to analyse the
      effect of pH modification on the morphology, corrosion behaviour and in vitro
      bioactivity and in vivo biocompatibility of hydroxyapatite prepared by ED on the
      additively manufactured Ti64 samples. The coatings prepared in the electrolytes
      with pH = 6 have predominantly needle like morphology with the dimensions in the
      nanometric scale (~30 nm). Samples coated at pH = 6 demonstrated higher
      protection efficiency against the corrosive attack as compared to the ones coated
      at pH = 5 (~93% against 89%). The in vitro bioactivity results indicated that
      both coatings have a greater capacity of biomineralization, compared to the
      uncoated Ti64. Somehow, the coating deposited at pH = 6 exhibited good corrosion
      behaviour and high biomineralization ability. In vivo subcutaneous implantation
      of the coated samples into the white rats for up to 21 days with following
      histological studies showed no serious inflammatory process.

PMID- 29196638
TI  - Uncovering different states of topological defects in schlieren textures of a
      nematic liquid crystal.
AB  - Topological defects are ubiquitously found in physical systems and therefore have
      been an important research subject of not only condensed matter physics but also
      cosmology. However, their fine structures remain elusive because of the
      microscopic scales involved. In the case of a liquid crystal, optical microscopy,
      although routinely used for the identification of liquid crystal phases and
      associated defects, does not have resolution high enough to distinguish fine
      structures of topological defects. Here we show that polarised and fluorescence
      microscopy, with the aid of numerical calculations on the orientational order and
      resulting image distortions, can uncover the structural states of topological
      defects with strength m =  +/-1 in a thin cell of a nematic liquid crystal.
      Particularly, defects with m = +1 exhibit four different states arising from
      chiral symmetry breaking and up-down symmetry breaking. Our results demonstrate
      that optical microscopy is still a powerful tool to identify fine states of
      liquid crystalline defects.

PMID- 29196640
TI  - Image Fiber-Based Miniature Suspended Solid Sensor with High Accuracy and a Large
      Dynamic Range.
AB  - An image fiber-based miniature suspended solid sensor has been demonstrated. The
      diameter of the sensor is only a few millimeters. A superhydrophobic material is
      coated on the end of the image fiber to avoid the adsorption of suspended solids
      and bubbles. Multiple parameters, including mass concentration, morphology and
      particle sizes of suspended solids, can be visually measured in real time.
      Dynamic ranges of 0 ~100 kg/m3, full range accuracies of +/-20/00 and a response
      time of 0.05 s were experimentally realized for the mass concentration
      measurements. Determinations of particle sizes of the suspended solids are also
      presented by means of digital image processing. This new technique will
      significantly advance ultralow-intrusion measurements in studies on the dynamics
      of suspended solids.

PMID- 29196639
TI  - Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and
      identifies potential new biologic subtype.
AB  - Consistent discrepancies in the p16/HPV-positivity have been observed in head and
      neck squamous cell carcinoma (HNSCC). It is therefore questionable, if all HPV+
      and/or p16+ tested cancers are HPV-driven. Patients down-staged according to the
      HPV-dependant TNM are at risk for undertreatment and data in clinical trials may
      be skewed due to false patient inclusion. We performed a meta-analysis to
      classify clinical outcomes of the distinct subgroups with combined p16 and HPV
      detection. 25 out of 1677 publications fulfilled the inclusion criteria. The
      proportion of the subgroups was 35.6% for HPV+/p16+, 50.4% for HPV-/p16-, 6.7%
      for HPV-/p16+ and 7.3% for HPV+/P16-. The HPV+/p16+ subgroup had a significantly
      improved 5-year overall-survival (OS) and disease-free-survival in comparison to
      others both for HNSCC and oropharyngeal cancers. The 5-year OS of the HPV-/p16+
      HNSCC was intermediate while HPV+/p16- and HPV-/p16- had the shortest survival
      outcomes. The clearly distinct survival of HPV-/p16+ cancers may characterize a
      new relevant HPV-independent subtype yet to be biologically characterized. The
      possibility also exists that in some HPV+/p16+ cancers HPV is an innocent
      bystander and p16 is independently positive. Therefore, in perspective, HPV
      testing should distinguish between bystander HPV and truly HPV-driven cancers to
      avoid potential undertreatment in HPV+ but non-HPV-driven HNSCC.

PMID- 29196641
TI  - Simultaneous realization of high sensing sensitivity and tunability in plasmonic
      nanostructures arrays.
AB  - A plasmonic nanostructure (PNS) which integrates metallic and dielectric media
      within a single structure has been shown to exhibit specific plasmonic properties
      which are considered useful in refractive index (RI) sensor applications. In this
      paper, the simultaneous realization of sensitivity and tunability of the optical
      properties of PNSs consisting of alternative Ag and dielectric of
      nanosphere/nanorod array have been proposed and compared by using three
      dimensional finite element method. The proposed system can support plasmonic
      hybrid modes and the localized surface plasmonic resonances and cavity plasmonic
      resonances within the individual PNS can be excited by the incident light. The
      proposed PNSs can be operated as RI sensor with a sensitivity of 500 nm/RIU (RIU
      = refractive index unit) ranging from UV to the near-infrared. In addition, a
      narrow bandwidth and nearly zero transmittance along with a high absorptance can
      be achieved by a denser PNSs configuration in the unit cell of PNS arrays. We
      have demonstrated the number of modes sustained in the PNS system, as well as,
      the near-field distribution can be tailored by the dielectric media in PNSs.

PMID- 29196642
TI  - A chalcohalide glass/alloy based Ag+ ion - selective electrode with nanomolar
      detection limit.
AB  - In this paper, a silver ion-selective electrode material with lower detection
      limit is presented. The electrode is based on 22.5As2S3-22.5Ag2S-55AgCl
      chalcohalide glass membranes. The low detection limit decreases from the
      micromolar range of the original Ag2S-As2S3 electrode to the nanomolar level
      (1.89 nM) by introducing AgCl. The addition of AgCl increases the conductivity of
      the glasses and improves the analytical properties of electrodes because of the
      joint effects of Ag+ and Cl- on network structure of the glass. The super
      Nernstian response behavior was observed for the partially crystallized
      electrode. The electrode containing AgCl also possesses a high selectivity
      (except for Hg2+), fast response and good stability.

PMID- 29196643
TI  - Blood Serum Calorimetry Indicates the Chemotherapeutic Efficacy in Lung Cancer
      Treatment.
AB  - Chemotherapy is a primary treatment for the metastatic lung cancer patients. To
      select the most effective combination of drugs, we need an efficient way of
      assessing tumor response. Here, we showed that differential scanning calorimetry
      (DSC) analysis of blood serum proteins could reveal the patient response to the
      treatment. If chemotherapy is effective, serum proteins DSC curve of non-small
      cellular lung cancer (NSCLC) case is similar to the those of the healthy
      individuals. If treatment fails, notable changes occur in the DSC profile of
      NSCLC patient's blood serum. Our preliminary work illustrates how thermal
      analysis of changes in the heat capacity of blood serum proteins can provide an
      insight into patient response to chemotherapy - the essential information for any
      successive lung cancer treatment.

PMID- 29196644
TI  - Adaptive laboratory evolution of Corynebacterium glutamicum towards higher growth
      rates on glucose minimal medium.
AB  - In this work, we performed a comparative adaptive laboratory evolution experiment
      of the important biotechnological platform strain Corynebacterium glutamicum ATCC
      13032 and its prophage-free variant MB001 towards improved growth rates on
      glucose minimal medium. Both strains displayed a comparable adaptation behavior
      and no significant differences in genomic rearrangements and mutation
      frequencies. Remarkably, a significant fitness leap by about 20% was observed for
      both strains already after 100 generations. Isolated top clones (UBw and UBm)
      showed an about 26% increased growth rate on glucose minimal medium. Genome
      sequencing of evolved clones and populations resulted in the identification of
      key mutations in pyk (pyruvate kinase), fruK (1-phosphofructokinase) and corA
      encoding a Mg2+ importer. The reintegration of selected pyk and fruK mutations
      resulted in an increased glucose consumption rate and ptsG expression causative
      for the accelerated growth on glucose minimal medium, whereas corA mutations
      improved growth under Mg2+ limiting conditions. Overall, this study resulted in
      the identification of causative key mutations improving the growth of C.
      glutamicum on glucose. These identified mutational hot spots as well as the two
      evolved top strains, UBw and UBm, represent promising targets for future
      metabolic engineering approaches.

PMID- 29196645
TI  - Small molecule screen in embryonic zebrafish using modular variations to target
      segmentation.
AB  - Small molecule in vivo phenotypic screening is used to identify drugs or
      biological activities by directly assessing effects in intact organisms. However,
      current screening designs may not exploit the full potential of chemical
      libraries due to false negatives. Here, we demonstrate a modular small molecule
      screen in embryonic zebrafish that varies concentration, genotype and timing to
      target segmentation disorders, birth defects that affect the spinal column. By
      testing each small molecule in multiple interrelated ways, this screen recovers
      compounds that a standard screening design would have missed, increasing the hit
      frequency from the chemical library three-fold. We identify molecular pathways
      and segmentation phenotypes, which we share in an open-access annotated database.
      These hits provide insight into human vertebral segmentation disorders and
      myopathies. This modular screening strategy is applicable to other developmental
      questions and disease models, highlighting the power of relatively small chemical
      libraries to accelerate gene discovery and disease study.

PMID- 29196646
TI  - Early-Mid Pleistocene genetic differentiation and range expansions as exemplified
      by invasive Eurasian Bunias orientalis (Brassicaceae) indicates the Caucasus as
      key region.
AB  - Turkish Warty cabbage, Bunias orientalis L. (Brassicaceae) is a perennial herb
      known for its 250 years of invasion history into Europe and worldwide temperate
      regions. Putative centers of origin were debated to be located in Turkey, the
      Caucasus or Eastern Europe. Based on the genetic variation from the nuclear and
      plastid genomes, we identified two major gene pools in the Caucasian-Irano
      Turanian region and close to the Northern Caucasus, respectively. These gene
      pools are old and started to diverge and expand approximately 930 kya in the
      Caucasus. Pleistocene glaciation and deglaciation cycles favoured later expansion
      of a European gene pool 230 kya, which was effectively separated from the
      Caucasian-Irano-Turanian gene pool. Although the European gene pool is
      genetically less diverse, it has largely served as source for colonization of
      Western and Northern Europe in modern times with rare observations of genetic
      contributions from the Caucasian-Irano-Turanian gene pool such as in North-East
      America. This study largely utilized herbarium material to take advantage of a
      biodiversity treasure trove providing biological material and also giving access
      to detailed collection information.

PMID- 29196648
TI  - Sequestosome1/p62 protects mouse embryonic fibroblasts against low-dose
      methylercury-induced cytotoxicity and is involved in clearance of ubiquitinated
      proteins.
AB  - Methylmercury (MeHg) is a widely distributed environmental pollutant that causes
      a series of cytotoxic effects. However, molecular mechanisms underlying MeHg
      toxicity are not fully understood. Here, we report that sequestosome1/p62
      protects mouse embryonic fibroblasts (MEFs) against low-dose MeHg cytotoxicity
      via clearance of MeHg-induced ubiquitinated proteins. p62 mRNA and protein
      expression in MEFs were temporally induced by MeHg exposure p62-deficient MEFs
      exhibited higher sensitivity to MeHg exposure compared to their wild-type (WT)
      counterparts. An earlier and higher level of accumulation of ubiquitinated
      proteins was detected in p62-deficient cells compared with WT MEFs. Confocal
      microscopy revealed that p62 and ubiquitinated proteins co-localized in the
      perinuclear region of MEFs following MeHg treatment. Further analysis of MEFs
      revealed that ubiquitinated proteins co-localized with LC3-positive puncta upon
      co-treatment with MeHg and chloroquine, an autophagy inhibitor. In contrast,
      there was minimal co-localization in p62-deficient MEFs. The present study, for
      the first time, examined the expression and distribution of p62 and ubiquitinated
      proteins in cells exposed to low-dose MeHg. Our findings suggest that p62 is
      crucial for cytoprotection against MeHg-induced toxicity and is required for MeHg
      induced ubiquitinated protein clearance.

PMID- 29196647
TI  - Injectable nanohydroxyapatite-chitosan-gelatin micro-scaffolds induce
      regeneration of knee subchondral bone lesions.
AB  - Subchondral bone has been identified as an attractive target for KOA. To
      determine whether a minimally invasive micro-scaffolds could be used to induce
      regeneration of knee subchondral bone lesions, and to examine the protective
      effect of subchondral bone regeneration on upper cartilage, a ready-to-use
      injectable treatment with nanohydroxyapatite-chitosan-gelatin micro-scaffolds
      (HaCGMs) is proposed. Human-infrapatellar-fat-pad-derived adipose stem cells
      (IPFP-ASCs) were used as a cellular model to examine the osteo-inductivity and
      biocompatibility of HaCGMs, which were feasibly obtained with potency for multi
      potential differentiations. Furthermore, a subchondral bone lesion model was
      developed to mimic the necrotic region removing performed by surgeons before
      sequestrectomy. HaCGMs were injected into the model to induce regeneration of
      subchondral bone. HaCGMs exhibited desirable swelling ratios, porosity,
      stiffness, and bioactivity and allowed cellular infiltration. Eight weeks after
      treatment, assessment via X-ray imaging, micro-CT imaging, and histological
      analysis revealed that rabbits treated with HaCGMs had better subchondral bone
      regeneration than those not treated. Interestingly, rabbits in the HaCGM
      treatment group also exhibited improved reservation of upper cartilage compared
      to those in other groups, as shown by safranin O-fast green staining. Present
      study provides an in-depth demonstration of injectable HaCGM-based regenerative
      therapy, which may provide an attractive alternative strategy for treating KOA.

PMID- 29196649
TI  - Molecular mechanisms of dysfunction of muscle fibres associated with Glu139
      deletion in TPM2 gene.
AB  - Deletion of Glu139 in beta-tropomyosin caused by a point mutation in TPM2 gene is
      associated with cap myopathy characterized by high myofilament Ca2+-sensitivity
      and muscle weakness. To reveal the mechanism of these disorders at molecular
      level, mobility and spatial rearrangements of actin, tropomyosin and the myosin
      heads at different stages of actomyosin cycle in reconstituted single ghost
      fibres were investigated by polarized fluorescence microscopy. The mutation did
      not alter tropomyosin's affinity for actin but increased strongly the flexibility
      of tropomyosin and kept its strands near the inner domain of actin. The ability
      of troponin to switch actin monomers "on" and "off" at high and low Ca2+,
      respectively, was increased, and the movement of tropomyosin towards the blocked
      position at low Ca2+ was inhibited, presumably causing higher Ca2+-sensitivity.
      The mutation decreased also the amount of the myosin heads which bound strongly
      to actin at high Ca2+ and increased the number of these heads at relaxation; this
      may contribute to contractures and muscle weakness.

PMID- 29196650
TI  - A polar bundle of flagella can drive bacterial swimming by pushing, pulling, or
      coiling around the cell body.
AB  - Bacteria swim in sequences of straight runs that are interrupted by turning
      events. They drive their swimming locomotion with the help of rotating helical
      flagella. Depending on the number of flagella and their arrangement across the
      cell body, different run-and-turn patterns can be observed. Here, we present
      fluorescence microscopy recordings showing that cells of the soil bacterium
      Pseudomonas putida that are decorated with a polar tuft of helical flagella, can
      alternate between two distinct swimming patterns. On the one hand, they can
      undergo a classical push-pull-push cycle that is well known from monopolarly
      flagellated bacteria but has not been reported for species with a polar bundle of
      multiple flagella. Alternatively, upon leaving the pulling mode, they can enter a
      third slow swimming phase, where they propel themselves with their helical bundle
      wrapped around the cell body. A theoretical estimate based on a random-walk model
      shows that the spreading of a population of swimmers is strongly enhanced when
      cycling through a sequence of pushing, pulling, and wrapped flagellar
      configurations as compared to the simple push-pull-push pattern.

PMID- 29196651
TI  - 3D photogrammetry quantifies growth and external erosion of individual coral
      colonies and skeletons.
AB  - Growth and contraction of ecosystem engineers, such as trees, influence ecosystem
      structure and function. On coral reefs, methods to measure small changes in the
      structure of microhabitats, driven by growth of coral colonies and contraction of
      skeletons, are extremely limited. We used 3D reconstructions to quantify changes
      in the external structure of coral colonies of tabular Acropora spp., the
      dominant habitat-forming corals in shallow exposed reefs across the Pacific. The
      volume and surface area of live colonies increased by 21% and 22%, respectively,
      in 12 months, corresponding to a mean annual linear extension of 5.62 cm yr-1 (+/
      1.81 SE). The volume and surface area of dead skeletons decreased by 52% and 47%,
      respectively, corresponding to a mean decline in linear extension of -29.56 cm yr
      1 (+/-7.08 SE), which accounted for both erosion and fragmentation of dead
      colonies. This is the first study to use 3D photogrammetry to assess fine-scale
      structural changes of entire individual colonies in situ, quantifying coral
      growth and contraction. The high-resolution of the technique allows for detection
      of changes on reef structure faster than other non-intrusive approaches. These
      results improve our capacity to measure the drivers underpinning ecosystem
      biodiversity, status and trajectory.

PMID- 29196652
TI  - Vacuum level dependent photoluminescence in chemical vapor deposition-grown
      monolayer MoS 2.
AB  - The stronger photoluminescence (PL) in chemical vapor deposition (CVD) grown
      monolayer MoS2 has been attributed to its high crystal quality compared with that
      in mechanically exfoliated (ME) crystal, which is contrary to the cognition that
      the ME crystal usually have better crystal quality than that of CVD grown one and
      it is expected with a better optical quality. In this report, the reason of
      abnormally strong PL spectra in CVD grown monolayer crystal is systematically
      investigated by studying the in-situ opto-electrical exploration at various
      environments for both of CVD and ME samples. High resolution transmission
      electron microscopy is used to investigate their crystal qualities. The stronger
      PL in CVD grown crystal is due to the high p-doping effect of adsorbates induced
      rebalance of exciton/trion emission. The first principle calculations are carried
      out to explore the interaction between adsorbates in ambient and defects sites in
      MoS2, which is consistent to the experimental phenomenon and further confirm our
      proposed mechanisms.

PMID- 29196653
TI  - New energy with ZnS: novel applications for a standard transparent compound.
AB  - We revise the electronic and optical properties of ZnS on the basis of first
      principles simulations, in view of novel routes for optoelectronic and photonic
      devices, such as transparent conductors and plasmonic applications. In
      particular, we consider doping effects, as induced by Al and Cu. It is shown that
      doping ZnS with Al imparts a n-character and allows for a plasmonic activity in
      the mid-IR that can be exploited for IR metamaterials, while Cu doping induces a
      spin dependent p-type character to the ZnS host, opening the way to the
      engineering of transparent p-n junctions, p-type transparent conductive materials
      and spintronic applications. The possibility of promoting the wurtzite lattice,
      presenting a different symmetry with respect to the most stable and common
      zincblende structure, is explored. Homo- and heterojunctions to twin ZnO are
      discussed as a possible route to transparent metamaterial devices for
      communications and energy.

PMID- 29196654
TI  - Cascading collapse of online social networks.
AB  - Online social networks have increasing influence on our society, they may play
      decisive roles in politics and can be crucial for the fate of companies. Such
      services compete with each other and some may even break down rapidly. Using
      social network datasets we show the main factors leading to such a dramatic
      collapse. At early stage mostly the loosely bound users disappear, later
      collective effects play the main role leading to cascading failures. We present a
      theory based on a generalised threshold model to explain the findings and show
      how the collapse time can be estimated in advance using the dynamics of the
      churning users. Our results shed light to possible mechanisms of instabilities in
      other competing social processes.

PMID- 29196655
TI  - Systematic identification of novel regulatory interactions controlling biofilm
      formation in the bacterium Escherichia coli.
AB  - Here, we investigated novel interactions of three global regulators of the
      network that controls biofilm formation in the model bacterium Escherichia coli
      using computational network analysis, an in vivo reporter assay and physiological
      validation experiments. We were able to map critical nodes that govern planktonic
      to biofilm transition and identify 8 new regulatory interactions for CRP, IHF or
      Fis responsible for the control of the promoters of rpoS, rpoE, flhD, fliA, csgD
      and yeaJ. Additionally, an in vivo promoter reporter assay and motility analysis
      revealed a key role for IHF as a repressor of cell motility through the control
      of FliA sigma factor expression. This investigation of first stage and mature
      biofilm formation indicates that biofilm structure is strongly affected by IHF
      and Fis, while CRP seems to provide a fine-tuning mechanism. Taken together, the
      analysis presented here shows the utility of combining computational and
      experimental approaches to generate a deeper understanding of the biofilm
      formation process in bacteria.

PMID- 29196656
TI  - Development of a plasmid free CRISPR-Cas9 system for the genetic modification of
      Mucor circinelloides.
AB  - Mucor circinelloides and other members of Mucorales are filamentous fungi, widely
      used as model organisms in basic and applied studies. Although genetic
      manipulation methods have been described for some Mucoral fungi, construction of
      stable integrative transformants by homologous recombination has remained a great
      challenge in these organisms. In the present study, a plasmid free CRISPR-Cas9
      system was firstly developed for the genetic modification of a Mucoral fungus.
      The described method offers a rapid but robust tool to obtain mitotically stable
      mutants of M. circinelloides via targeted integration of the desired DNA. It does
      not require plasmid construction and its expression in the recipient organism.
      Instead, it involves the direct introduction of the guide RNA and the Cas9 enzyme
      and, in case of homology directed repair (HDR), the template DNA into the
      recipient strain. Efficiency of the method for non-homologous end joining (NHEJ)
      and HDR was tested by disrupting two different genes, i.e. carB encoding phytoene
      dehydrogenase and hmgR2 encoding 3-hydroxy-3-methylglutaryl-CoA reductase, of M.
      circinelloides. Both NHEJ and HDR resulted in stable gene disruption mutants.
      While NHEJ caused extensive deletions upstream from the protospacer adjacent
      motif, HDR assured the integration of the deletion cassette at the targeted site.

PMID- 29196657
TI  - Alternative activation generates IL-10 producing type 2 innate lymphoid cells.
AB  - Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor
      expression with CD4+ Th2 cells, but functional diversity of the ILC2 lineage has
      yet to be fully explored. Here, we show induction of a molecularly distinct
      subset of activated lung ILC2, termed ILC210. These cells produce IL-10 and
      downregulate some pro-inflammatory genes. Signals that generate ILC210 are
      distinct from those that induce IL-13 production, and gene expression data
      indicate that an alternative activation pathway leads to the generation of
      ILC210. In vivo, IL-2 enhances ILC210 generation and is associated with decreased
      eosinophil recruitment to the lung. Unlike most activated ILC2, the ILC210
      population contracts after cessation of stimulation in vivo, with maintenance of
      a subset that can be recalled by restimulation, analogous to T-cell effector cell
      and memory cell generation. These data demonstrate the generation of a previously
      unappreciated IL-10 producing ILC2 effector cell population.

PMID- 29196658
TI  - Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue.
AB  - Vascular endothelial growth factor A (VEGFA) is a key factor in the regulation of
      angiogenesis in adipose tissue. Poor vascularization during adipose tissue
      proliferation causes fibrosis and local inflammation, and is associated with
      insulin resistance. It is known that 17-beta estradiol (E2) regulates adipose
      tissue function and VEGFA expression in other tissues; however, the ability of E2
      to regulate VEGFA in adipose tissue is currently unknown. In this study, we
      showed that, in 3T3-L1 cells, E2 and the estrogen receptor 1 (ESR1) agonist PPT
      induced VEGFA expression, while ESR1 antagonist (MPP), and selective knockdown of
      ESR1 using siRNA decreased VEGFA and prevented the ability of E2 to modulate its
      expression. Additionally, we found that E2 and PPT induced the binding of hypoxia
      inducible factor 1 alpha subunit (HIF1A) in the VEGFA gene promoter. We further
      found that VEGFA expression was lower in inguinal and gonadal white adipose
      tissues of ESR1 total body knockout female mice compared to wild type mice. In
      conclusion, our data provide evidence of an important role for E2/ESR1 in
      modulating adipose tissue VEGFA, which is potentially important to enhance
      angiogenesis, reduce inflammation and improve adipose tissue function.

PMID- 29196659
TI  - Rational design and dynamics of self-propelled colloidal bead chains: from
      rotators to flagella.
AB  - The quest for designing new self-propelled colloids is fuelled by the demand for
      simple experimental models to study the collective behaviour of their more
      complex natural counterparts. Most synthetic self-propelled particles move by
      converting the input energy into translational motion. In this work we address
      the question if simple self-propelled spheres can assemble into more complex
      structures that exhibit rotational motion, possibly coupled with translational
      motion as in flagella. We exploit a combination of induced dipolar interactions
      and a bonding step to create permanent linear bead chains, composed of self
      propelled Janus spheres, with a well-controlled internal structure. Next, we
      study how flexibility between individual swimmers in a chain can affect its
      swimming behaviour. Permanent rigid chains showed only active rotational or
      spinning motion, whereas longer semi-flexible chains showed both translational
      and rotational motion resembling flagella like-motion, in the presence of the
      fuel. Moreover, we are able to reproduce our experimental results using numerical
      calculations with a minimal model, which includes full hydrodynamic interactions
      with the fluid. Our method is general and opens a new way to design novel self
      propelled colloids with complex swimming behaviours, using different complex
      starting building blocks in combination with the flexibility between them.

PMID- 29196660
TI  - Transcriptome analysis of watermelon (Citrullus lanatus) fruits in response to
      Cucumber green mottle mosaic virus (CGMMV) infection.
AB  - Cucumber green mottle mosaic virus (CGMMV) belongs to the Tobamovirus genus and
      is a major global plant virus on cucurbit plants. It causes severe disease
      symptoms on infected watermelon plants (Citrullus lanatus), particularly inducing
      fruit decay. However, little is known about the molecular mechanism of CGMMV
      induced watermelon fruit decay. For this study, comparative analysis of
      transcriptome profiles of CGMMV-inoculated and mock-inoculated watermelon fruits
      were conducted via RNA-Seq. A total of 1,621 differently expressed genes (DEGs)
      were identified in CGMMV-inoculated watermelon, among which 1,052 were up
      regulated and 569 were down-regulated. Functional annotation analysis showed that
      several DEGs were involved in carbohydrate metabolism, hormone biosynthesis and
      signaling transduction, secondary metabolites biosynthesis, and plant-pathogen
      interactions. We furthermore found that some DEGs were related to cell wall
      components and photosynthesis, which may directly be involve in the development
      of the symptoms associated with diseased watermelons. To confirm the RNA-Seq
      data, 15 DEGs were selected for gene expression analysis by qRT-PCR. The results
      showed a strong correlation between these two sets of data. Our study identified
      many candidate genes for further functional studies during CGMMV-watermelon
      interactions, and will furthermore help to clarify the understanding of
      pathogenic mechanism underlying CGMMV infection in cucurbit plants.

PMID- 29196661
TI  - fMRI Investigation on Gradual Change of Awareness States in Implicit Sequence
      Learning.
AB  - Awareness of implicit knowledge is a changing process. Previous studies have
      examined brain activation patterns corresponding to the start and end stages of
      implicit learning, but failed to reveal the gradual changing course of awareness
      in implicit learning. The present study explored brain activation changes
      corresponding to different awareness states elicited by two different stimulus
      onset asynchrony (SOA, 850 ms and 1350 ms) over the whole course of implicit
      sequence learning (i.e., divided into three phases), by using a process
      dissociation procedure (PDP) paradigm and the technique of functional magnetic
      resonance imaging (fMRI). In the results, it was found that the 850 ms SOA
      elicited primarily an awareness state of unconsciousness, under which the frontal
      lobe was significantly activated during the early phase of implicit sequence
      learning, with its activation levels correlated positively to consciousness
      levels. In contrast, the 1350 ms SOA triggered predominantly an awareness state
      of consciousness, under which the activation levels of the inferior parietal
      lobule correlated positively to consciousness levels during the middle phase, and
      positively to consciousness levels as well as negatively to unconsciousness
      levels during the late phase of implicit sequence learning. Overall, the frontal
      lobe and inferior parietal lobule were found to play critical roles in mediating
      awareness states over the course of implicit sequence learning.

PMID- 29196662
TI  - Toehold-enhanced LNA probes for selective pull down and single-molecule analysis
      of native chromatin.
AB  - The organization of DNA into chromatin is thought to regulate gene expression in
      eukaryotes. To study its structure in vitro, there is a need for techniques that
      can isolate specific chromosomal loci of natively assembled chromatin. Current
      purification methods often involve chemical cross-linking to preserve the
      chromatin composition. However, such cross-linking may affect the native
      structure. It also impedes single molecule force spectroscopy experiments, which
      have been instrumental to probe chromatin folding. Here we present a method for
      the incorporation of affinity tags, such as biotin, into native nucleoprotein
      fragments based on their DNA sequence, and subsequent single molecule analysis by
      magnetic tweezers. DNA oligos with several Locked Nucleic Acid (LNA) nucleotides
      are shown to selectively bind to target DNA at room temperature, mediated by a
      toehold end in the target, allowing for selective purification of DNA fragments.
      The stability of the probe-target hybrid is sufficient to withstand over 65 pN of
      force. We employ these probes to obtain force-extension curves of native
      chromatin fragments of the 18S ribosomal DNA from the yeast Saccharomyces
      cerevisiae. These experiments yield valuable insights in the heterogeneity in
      structure and composition of natively assembled chromatin at the single-molecule
      level.

PMID- 29196663
TI  - A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss
      of retinal ganglion cells in mice.
AB  - Src knockout mice show no detectable abnormalities in central nervous system
      (CNS) post-mitotic neurons, likely reflecting functional compensation by other
      Src family kinases. Cdk1- or Cdk5-dependent Ser75 phosphorylation in the amino
      terminal Unique domain of Src, which shares no homology with other Src family
      kinases, regulates the stability of active Src. To clarify the roles of Src Ser75
      phosphorylation in CNS neurons, we established two types of mutant mice with
      mutations in Src: phospho-mimicking Ser75Asp (SD) and non-phosphorylatable
      Ser75Ala (SA). In ageing SD/SD mice, retinal ganglion cell (RGC) number in whole
      retinas was significantly lower than that in young SD/SD mice in the absence of
      inflammation and elevated intraocular pressure, resembling the pathogenesis of
      progressive optic neuropathy. By contrast, SA/SA mice and wild-type (WT) mice
      exhibited no age-related RGC loss. The age-related retinal RGC number reduction
      was greater in the peripheral rather than the mid-peripheral region of the retina
      in SD/SD mice. Furthermore, Rho-associated kinase activity in whole retinas of
      ageing SD/SD mice was significantly higher than that in young SD/SD mice. These
      results suggest that Src regulates RGC survival during ageing in a manner that
      depends on Ser75 phosphorylation.

PMID- 29196664
TI  - The origin of human handedness and its role in pre-birth motor control.
AB  - The vast majority of humans are right-handed, but how and when this bias emerges
      during human ontogenesis is still unclear. We propose an approach that explains
      postnatal handedness starting from 18 gestational weeks using a kinematic
      analysis of different fetal arm movements recorded during ultrasonography. Based
      on the hand dominance reported postnatally at age 9, the fetuses were classified
      as right-handed (86%) or left-handed, in line with population data. We revealed
      that both right-handed and left-handed fetuses were faster to reach to targets
      requiring greater precision (i.e., eye and mouth), with their dominant (vs. non
      dominant) hand. By using either movement times or deceleration estimates,
      handedness can be inferred with a classification accuracy ranging from 89 to 100%
      from gestational week 18. The reliability of this inference hints to the yet
      unexplored potential of standard ultrasonography to advance our understanding of
      prenatal life.

PMID- 29196665
TI  - Antibunching-like behavior of mesoscopic light.
AB  - We present the implementation of a compact setup for the generation of sub
      Poissonian states of light exhibiting the analogous of antibunching behavior in
      the so-called mesoscopic intensity domain. In the scheme, the idler arm of a
      pulsed multi-mode twin-beam state is directly measured by a photon-number
      resolving detector, whereas the signal arm is divided at a balanced beam
      splitter, at whose outputs other two photon-number-resolving detectors measure
      the number of photons. The three detectors measure synchronous with each laser
      pulse. Due to the nonclassical correlations in the twin beam, when a given value
      of photons is measured in the idler arm, the conditional states obtained in post
      processing at the two beam-splitter outputs are nonclassical, showing lower-than
      one values of the Fano factor and of the photon autocorrelation coefficient. The
      possibility to engineer sub-Poissonian states nearly approaching the Fock state
      with one photon is also addressed.

PMID- 29196666
TI  - Sigma frequency dependent motor learning in Williams syndrome.
AB  - There are two basic stages of fine motor learning: performance gain might occur
      during practice (online learning), and improvement might take place without any
      further practice (offline learning). Offline learning, also called consolidation,
      has a sleep-dependent stage in terms of both speed and accuracy of the learned
      movement. Sleep spindle or sigma band characteristics affect motor learning in
      typically developing individuals. Here we ask whether the earlier found, altered
      sigma activity in a neurodevelopmental disorder (Williams syndrome, WS) predicts
      motor learning. TD and WS participants practiced in a sequential finger tapping
      (FT) task for two days. Although WS participants started out at a lower
      performance level, TD and WS participants had a comparable amount of online and
      offline learning in terms of the accuracy of movement. Spectral analysis of WS
      sleep EEG recordings revealed that motor accuracy improvement is intricately
      related to WS-specific NREM sleep EEG features in the 8-16 Hz range profiles:
      higher 11-13.5 Hz z-transformed power is associated with higher offline FT
      accuracy improvement; and higher oscillatory peak frequencies are associated with
      lower offline accuracy improvements. These findings indicate a fundamental
      relationship between sleep spindle (or sigma band) activity and motor learning in
      WS.

PMID- 29196667
TI  - A multidisciplinary approach to study the reproductive biology of wild prawns.
AB  - This work aims to provide deeper knowledge on reproductive biology of P.
      kerathurus in a multidisciplinary way. Upon 789 examined females, 285 were found
      inseminated. The logistic equation enabled to estimate the size at first maturity
      at 30.7 mm CL for female. The Gono-Somatic Index (GSI) showed a pronounced
      seasonality, ranged from 0.80 +/- 0.34 to 11.24 +/- 5.72. Histological analysis
      highlighted five stages of ovarian development. Gonadal fatty acids analysis
      performed with gas chromatograph evidenced a pronounced seasonal variation; total
      lipids varied from 1.7% dry weight (dw) in Winter, to 7.2% dw in Summer. For the
      first time, a chemometric approach (Principal Component Analysis) was applied to
      relate GSI with total lipid content and fatty acid composition of gonads. The
      first two components (PC1 and PC2) showed that seasonality explained about 84% of
      the variability of all data set. In particular, in the period February-May,
      lipids were characterized by high PUFAs content, that were probably utilized
      during embryogenesis as energy source and as constituent of the cell membranes.
      During the summer season, gonads accumulated saturated FAs, that will be used
      during embryogenesis and early larval stages, while in the cold season total
      lipids decreased drastically and the gonad reached a quiescent state.

PMID- 29196668
TI  - Adrenergic receptor agonists induce the differentiation of pluripotent stem cell
      derived hepatoblasts into hepatocyte-like cells.
AB  - Current induction methods of hepatocytes from human induced pluripotent stem
      cells (hiPSCs) are neither low cost nor stable. By screening a chemical library
      of 1,120 bioactive compounds and known drugs, we identified the alpha1-adrenergic
      receptor agonist methoxamine hydrochloride as a small molecule that promotes the
      differentiation of hiPSC-derived hepatoblasts into ALBUMIN+ hepatocyte-like
      cells. Other alpha1-adrenergic receptor agonists also induced the differentiation
      of hepatocyte-like cells, and an alpha1-receptor antagonist blocked the hepatic
      inducing activity of methoxamine hydrochloride and that of the combination of
      hepatocyte growth factor (HGF) and Oncostatin M (OsM), two growth factors often
      used for the induction of hepatoblasts into hepatocyte-like cells. We also
      confirmed that treatment with methoxamine hydrochloride activates the signal
      transducer and activator of transcription 3 (STAT3) pathway downstream of IL-6
      family cytokines including OsM. These findings allowed us to establish hepatic
      differentiation protocols for both mouse embryonic stem cells (mESCs) and hiPSCs
      using small molecules at the step from hepatoblasts into hepatocyte-like cells.
      The results of the present study suggest that alpha1-adrenergic agonists induce
      hepatocyte-like cells by working downstream of HGF and OsM to activate STAT3.

PMID- 29196669
TI  - Author Correction: Down-regulation of cholinergic signaling in the habenula
      induces anhedonia-like behavior.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29196670
TI  - Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients
      from Greece.
AB  - Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder causing
      benign tumors in the brain and other vital organs. The genes implicated in
      disease development are TSC1 and TSC2. Here, we have performed mutational
      analysis followed by a genotype-phenotype correlation study based on the clinical
      characteristics of the affected individuals. Twenty unrelated probands or
      families from Greece have been analyzed, of whom 13 had definite TSC, whereas
      another 7 had a possible TSC diagnosis. Using direct sequencing, we have
      identified pathogenic mutations in 13 patients/families (6 in TSC1 and 7 in
      TSC2), 5 of which were novel. The mutation identification rate for patients with
      definite TSC was 85%, but only 29% for the ones with a possible TSC diagnosis.
      Multiplex ligation-dependent probe amplification (MLPA) did not reveal any
      genomic rearrangements in TSC1 and TSC2 in the samples with no mutations
      identified. In general, TSC2 disease was more severe than TSC1, with more
      subependymal giant cell astrocytomas and angiomyolipomas, higher incidence of
      pharmacoresistant epileptic seizures, and more severe neuropsychiatric disorders.
      To our knowledge, this is the first comprehensive TSC1 and TSC2 mutational
      analysis carried out in TSC patients in Greece.

PMID- 29196671
TI  - Concurrent structural and biophysical traits link with immunoglobulin light
      chains amyloid propensity.
AB  - Light chain amyloidosis (AL), the most common systemic amyloidosis, is caused by
      the overproduction and the aggregation of monoclonal immunoglobulin light chains
      (LC) in target organs. Due to genetic rearrangement and somatic hypermutation,
      virtually, each AL patient presents a different amyloidogenic LC. Because of such
      complexity, the fine molecular determinants of LC aggregation propensity and
      proteotoxicity are, to date, unclear; significantly, their decoding requires
      investigating large sets of cases. Aiming to achieve generalizable observations,
      we systematically characterised a pool of thirteen sequence-diverse full length
      LCs. Eight amyloidogenic LCs were selected as responsible for severe cardiac
      symptoms in patients; five non-amyloidogenic LCs were isolated from patients
      affected by multiple myeloma. Our comprehensive approach (consisting of
      spectroscopic techniques, limited proteolysis, and X-ray crystallography) shows
      that low fold stability and high protein dynamics correlate with amyloidogenic
      LCs, while hydrophobicity, structural rearrangements and nature of the LC dimeric
      association interface (as observed in seven crystal structures here presented) do
      not appear to play a significant role in defining amyloid propensity. Based on
      the structural and biophysical data, our results highlight shared properties
      driving LC amyloid propensity, and these data will be instrumental for the design
      of synthetic inhibitors of LC aggregation.

PMID- 29196672
TI  - Network Properties in Transitions of Consciousness during Propofol-induced
      Sedation.
AB  - Reliable electroencephalography (EEG) signatures of transitions between
      consciousness and unconsciousness under anaesthesia have not yet been identified.
      Herein we examined network changes using graph theoretical analysis of high
      density EEG during patient-titrated propofol-induced sedation. Responsiveness was
      used as a surrogate for consciousness. We divided the data into five states:
      baseline, transition into unresponsiveness, unresponsiveness, transition into
      responsiveness, and recovery. Power spectral analysis showed that delta power
      increased from responsiveness to unresponsiveness. In unresponsiveness, delta
      waves propagated from frontal to parietal regions as a traveling wave. Local
      increases in delta connectivity were evident in parietal but not frontal regions.
      Graph theory analysis showed that increased local efficiency could differentiate
      the levels of responsiveness. Interestingly, during transitions of responsive
      states, increased beta connectivity was noted relative to consciousness and
      unconsciousness, again with increased local efficiency. Abrupt network changes
      are evident in the transitions in responsiveness, with increased beta band
      power/connectivity marking transitions between responsive states, while the delta
      power/connectivity changes were consistent with the fading of consciousness using
      its surrogate responsiveness. These results provide novel insights into the
      neural correlates of these behavioural transitions and EEG signatures for
      monitoring the levels of consciousness under sedation.

PMID- 29196673
TI  - Proton gradients and pH oscillations emerge from heat flow at the microscale.
AB  - Proton gradients are essential for biological systems. They not only drive the
      synthesis of ATP, but initiate molecule degradation and recycling inside
      lysosomes. However, the high mobility and permeability of protons through
      membranes make pH gradients very hard to sustain in vitro. Here we report that
      heat flow across a water-filled chamber forms and sustains stable pH gradients.
      Charged molecules accumulate by convection and thermophoresis better than
      uncharged species. In a dissociation reaction, this imbalances the reaction
      equilibrium and creates a difference in pH. In solutions of amino acids,
      phosphate, or nucleotides, we achieve pH differences of up to 2 pH units. The
      same mechanism cycles biomolecules by convection in the created proton gradient.
      This implements a feedback between biomolecules and a cyclic variation of the pH.
      The finding provides a mechanism to create a self-sustained proton gradient to
      drive biochemical reactions.

PMID- 29196674
TI  - Artificial controlled model of blood circulation system for adhesive evaluation.
AB  - Since there are several casualties due to uncontrolled bleeding resulting from
      simple injury to surgery, effective styptic or vessel adhesives are important;
      however, their development is limited by the lack of standardized systems to
      evaluate potential compounds. The current study outlines the development of an
      aorta styptic evaluation system, comprising of decellularized swine aorta tissue
      and a heart pump-mimicking system. Although the cells in the swine aorta were
      removed, the structural stability of the aorta was sustained due to the
      maintenance of the extracellular matrix. Using a control adhesive, Cyanoacrylate,
      the developed model was found to have similar adhesive efficacy to intact aorta.
      The circulatory-mimicking system was designed to mimic the beat rate and strength
      of blood-flow from the heart, which was necessary to evaluate the adherent
      efficacy. The decellularized aorta improves instabilities of intact tissues,
      which occurs on account of storage and origin, thereby allowing for a more
      standardized system. The system was able to simulate several symptoms of
      circulation, according to patient age and health, by adjusting pumping frequency
      and intensity. Therefore, this system can be used as a standardized evaluation
      system for screening adhesives. Further, it would also evaluate other medical
      devices, such as stent or medications.

PMID- 29196675
TI  - Low temperature and low salinity drive putatively adaptive growth differences in
      populations of threespine stickleback.
AB  - Colonisation can expose organisms to novel combinations of abiotic and biotic
      factors and drive adaptive divergence. Yet, studies investigating the interactive
      effects of multiple abiotic factors on the evolution of physiological traits
      remain rare. Here we examine the effects of low salinity, low temperature, and
      their interaction on the growth of three North American populations of threespine
      stickleback (Gasterosteus aculeatus). In north-temperate freshwater habitats,
      stickleback populations experience a combination of low salinity and low winter
      temperatures that are not experienced by the ancestral marine and anadromous
      populations. Here we show that both salinity and temperature, and their
      interaction, have stronger negative effects on marine and anadromous populations
      than a freshwater population. Freshwater stickleback showed only a ~20% reduction
      in specific growth rate when exposed to 4  degrees C, while marine and anadromous
      stickleback showed sharp declines (82% and 74% respectively) under these
      conditions. The modest decreases in growth in freshwater stickleback in fresh
      water in the cold strongly suggest that this population has the capacity for
      physiological compensation to offset the negative thermodynamic effects of low
      temperature on growth. These results are suggestive of adaptive evolution in
      response to the interactive effects of low salinity and low temperature during
      freshwater colonisation.

PMID- 29196676
TI  - Efficiency of novel nanocombinations of bovine milk proteins (lactoperoxidase and
      lactoferrin) for combating different human cancer cell lines.
AB  - Bovine lactoperoxidase (LPO) and lactoferrin (LF) are suitable proteins to be
      loaded or adsorbed to chitosan nanoparticles (NPs) for preparing stable
      nanoformulations with potent anticancer activity. In the present study,
      nanocombinations of LPO and LF revealed improvement in their stability and
      activity compared to single (free or nanoformulated) bovine proteins. The coating
      or loading of LPO-loaded NPs with LF resulted in the highest synergistic
      cytotoxicity effect against Caco-2, HepG-2, MCF-7 and PC-3 cells in comparison
      with other NPs and free proteins without causing toxicity toward normal cells.
      This synergistic improvement in the anticancer activity was apoptosis-dependent
      that was confirmed by severe alterations in cellular morphology, high percentage
      of annexin-stained cells and sub-G1 populations as well as nuclear staining with
      orange fluorescence of treated cancer cells. Additionally, significant
      alterations in the expression of well characterized cellular proliferation and
      apoptosis guards (NF-kappaB, Bcl-2 and p53) in these NPs-treated cancer cells
      compared to 5-fluorouracil (5-FU) treated cells. Our findings provide for the
      first time that these new synergistic nanoformulated forms of LPO and LF were
      superior in their selective apoptosis-mediating anticancer effect than free form
      of these proteins and 5-FU. LF coating or loading of LPO-loaded NPs present as
      promising therapy for cancer.

PMID- 29196677
TI  - Enhancement and suppression of turbulence by energetic-particle-driven geodesic
      acoustic modes.
AB  - We propose a novel mechanism of enhancement of turbulence by energetic-particle
      driven geodesic acoustic modes (EGAMs). The dynamics of drift-wave-type
      turbulence in the phase space is investigated by wave-kinetic equation. Spatially
      inhomogeneous turbulence in the presence of a transport barrier is considered. We
      discovered that trapping of turbulence clumps by the EGAMs is the key parameter
      that determines either suppress or enhance turbulence. In regions where
      turbulence is unstable, EGAM suppresses the turbulence. In contrast, in the
      stable region, EGAM traps clumps of turbulence and carries them across the
      transport barrier, so that the turbulence can be enhanced. The turbulence trapped
      by EGAMs can propagate independent of the gradients of density and temperature,
      which leads to non-Fickian transport. Hence, there appear a new global
      characteristic velocity, the phase velocity of GAMs, for turbulence dynamics, in
      addition to the local group velocity and that of the turbulence spreading. With
      these effect, EGAMs can deteriorate transport barriers and affect turbulence
      substantially. This manuscript provides a basis to consider whether a coherent
      wave breaks or strengthen transport barriers.

PMID- 29196678
TI  - Resolving kangaroo phylogeny and overcoming retrotransposon ascertainment bias.
AB  - Reconstructing phylogeny from retrotransposon insertions is often limited by
      access to only a single reference genome, whereby support for clades that do not
      include the reference taxon cannot be directly observed. Here we have developed a
      new statistical framework that accounts for this ascertainment bias, allowing us
      to employ phylogenetically powerful retrotransposon markers to explore the
      radiation of the largest living marsupials, the kangaroos and wallabies of the
      genera Macropus and Wallabia. An exhaustive in silico screening of the tammar
      wallaby (Macropus eugenii) reference genome followed by experimental screening
      revealed 29 phylogenetically informative retrotransposon markers belonging to a
      family of endogenous retroviruses. We identified robust support for the enigmatic
      swamp wallaby (Wallabia bicolor) falling within a paraphyletic genus, Macropus.
      Our statistical approach provides a means to test for incomplete lineage sorting
      and introgression/hybridization in the presence of the ascertainment bias. Using
      retrotransposons as "molecular fossils", we reveal one of the most complex
      patterns of hemiplasy yet identified, during the rapid diversification of
      kangaroos and wallabies. Ancestral state reconstruction incorporating the new
      retrotransposon phylogenetic information reveals multiple independent ecological
      shifts among kangaroos into more open habitats, coinciding with the Pliocene
      onset of increased aridification in Australia from ~3.6 million years ago.

PMID- 29196679
TI  - A Synthetic Population for Modelling the Dynamics of Infectious Disease
      Transmission in American Samoa.
AB  - Agent-based modelling is a useful approach for capturing heterogeneity in disease
      transmission. In this study, a synthetic population was developed for American
      Samoa using an iterative approach based on population census, questionnaire
      survey and land use data. The population will be used as the basis for a new
      agent-based model, intended specifically to fill the knowledge gaps about
      lymphatic filariasis transmission and elimination, but also to be readily
      adaptable to model other infectious diseases. The synthetic population was
      characterized by the statistically realistic population and household structure,
      and high-resolution geographic locations of households. The population was
      simulated over 40 years from 2010 to 2050. The simulated population was compared
      to estimates and projections of the U.S. Census Bureau. The results showed the
      total population would continuously decrease due to the observed large number of
      emigrants. Population ageing was observed, which was consistent with the latest
      two population censuses and the Bureau's projections. The sex ratios by age
      groups were analysed and indicated an increase in the proportion of males in age
      groups 0-14 and 15-64. The household size followed a Gaussian distribution with
      an average size of around 5.0 throughout the simulation, slightly less than the
      initial average size 5.6.

PMID- 29196680
TI  - Greenhouse gas emissions and carbon sequestration by agroforestry systems in
      southeastern Brazil.
AB  - Agrosilvopastoral and silvopastoral systems can increase carbon sequestration,
      offset greenhouse gas (GHG) emissions and reduce the carbon footprint generated
      by animal production. The objective of this study was to estimate GHG emissions,
      the tree and grass aboveground biomass production and carbon storage in different
      agrosilvopastoral and silvopastoral systems in southeastern Brazil. The number of
      trees required to offset these emissions were also estimated. The GHG emissions
      were calculated based on pre-farm (e.g. agrochemical production, storage, and
      transportation), and on-farm activities (e.g. fertilization and machinery
      operation). Aboveground tree grass biomass and carbon storage in all systems was
      estimated with allometric equations. GHG emissions from the agroforestry systems
      ranged from 2.81 to 7.98 t CO2e ha-1. Carbon storage in the aboveground trees and
      grass biomass were 54.6, 11.4, 25.7 and 5.9 t C ha-1, and 3.3, 3.6, 3.8 and 3.3 t
      C ha-1 for systems 1, 2, 3 and 4, respectively. The number of trees necessary to
      offset the emissions ranged from 17 to 44 trees ha-1, which was lower than the
      total planted in the systems. Agroforestry systems sequester CO2 from the
      atmosphere and can help the GHG emission-reduction policy of the Brazilian
      government.

PMID- 29196681
TI  - Structural responses of metallic glasses under neutron irradiation.
AB  - Seeking nuclear materials that possess a high resistance to particle irradiation
      damage is a long-standing issue. Permanent defects, induced by irradiation, are
      primary structural changes, the accumulation of which will lead to structural
      damage and performance degradation in crystalline materials served in nuclear
      plants. In this work, structural responses of neutron irradiation in metallic
      glasses (MGs) have been investigated by making a series of experimental
      measurements, coupled with simulations in ZrCu amorphous alloys. It is found
      that, compared with crystalline alloys, MGs have some specific structural
      responses to neutron irradiation. Although neutron irradiation can induce
      transient vacancy-like defects in MGs, they are fully annihilated after
      structural relaxation by rearrangement of free volumes. In addition, the
      rearrangement of free volumes depends strongly on constituent elements. In
      particular, the change in free volumes occurs around the Zr atoms, rather than
      the Cu centers. This implies that there is a feasible strategy for identifying
      glassy materials with high structural stability against neutron irradiation by
      tailoring the microstructures, the systems, or the compositions in alloys. This
      work will shed light on the development of materials with high irradiation
      resistance.

PMID- 29196682
TI  - On the proportional abundance of species: Integrating population genetics and
      community ecology.
AB  - The frequency of genes in interconnected populations and of species in
      interconnected communities are affected by similar processes, such as birth,
      death and immigration. The equilibrium distribution of gene frequencies in
      structured populations is known since the 1930s, under Wright's metapopulation
      model known as the island model. The equivalent distribution for the species
      frequency (i.e. the species proportional abundance distribution (SPAD)), at the
      metacommunity level, however, is unknown. In this contribution, we develop a
      stochastic model to analytically account for this distribution (SPAD). We show
      that the same as for genes SPAD follows a beta distribution, which provides a
      good description of empirical data and applies across a continuum of scales. This
      stochastic model, based upon a diffusion approximation, provides an alternative
      to neutral models for the species abundance distribution (SAD), which focus on
      number of individuals instead of proportions, and demonstrate that the relative
      frequency of genes in local populations and of species within communities follow
      the same probability law. We hope our contribution will help stimulate the
      mathematical and conceptual integration of theories in genetics and ecology.

PMID- 29196683
TI  - Preferential selection of Arginine at the lipid-water-interface of TRPV1 during
      vertebrate evolution correlates with its snorkeling behaviour and cholesterol
      interaction.
AB  - TRPV1 is a thermo-sensitive ion channel involved in neurosensory and other
      physiological functions. The trans-membrane helices of TRPV1 undergo quick and
      complex conformational changes governed by thermodynamic parameters and membrane
      components leading to channel opening. However, the molecular mechanisms
      underlying such events are poorly understood. Here we analysed the molecular
      evolution of TRPV1 at the lipid-water-interface region (LWI), typically defined
      as a layer of 6 A thickness on each side of the membrane with less availability
      of free water. Amino acids demarcating the end of the trans-membrane helices are
      highly conserved. Residues present in the inner leaflet are more conserved and
      have been preferentially selected over others. Amino acids with snorkeling
      properties (Arginine and Tyrosine) undergo specific selection during the
      vertebrate evolution in a cholesterol-dependent and/or body temperature manner.
      Results suggest that H-bond formation between the OH- group of cholesterol and
      side chain of Arg557 or Arg575 at the inner leaflet is a critical parameter that
      can regulate channel functions. Different LWI mutants of TRPV1 have altered
      membrane localization and deficient colocalization with lipid raft markers. These
      findings may help to understand the lipid-protein interactions, and molecular
      basis of different neuronal functions. Such findings may have broad importance in
      the context of differential sensory responses, pathophysiologies, and application
      of pharmacological drugs such as anaesthetics acting on TRPVs.

PMID- 29196684
TI  - Squalene epoxidase plays a critical role in determining pig meat quality by
      regulating adipogenesis, myogenesis, and ROS scavengers.
AB  - In mammals, Squalene epoxidase (SQLE) is an enzyme that converts squalene to 2,3
      oxidosqualene, in the early stage of cholesterol generation. Here, we identified
      single nucleotide polymorphisms (SNPs) in the SQLE gene (c.2565 G > T) by RNA
      Sequencing from the liver tissue of Berkshire pigs. Furthermore, we found that
      homozygous GG pigs expressed more SQLE mRNA than GT heterozygous and TT
      homozygous pigs in longissimus dorsi tissue. Next, we showed that the SNP in the
      SQLE gene was associated with several meat quality traits including backfat
      thickness, carcass weight, meat colour (yellowness), fat composition, and water
      holding capacity. Rates of myogenesis and adipogenesis induced in C2C12 cells and
      3T3-L1 cells, respectively, were decreased by Sqle knockdown. Additionally, the
      expression of myogenic marker genes (Myog, Myod, and Myh4) and adipogenic marker
      genes (Pparg, Cebpa, and Adipoq) was substantially downregulated in cells
      transfected with Sqle siRNA. Moreover, mRNA expression levels of ROS scavengers,
      which affect meat quality by altering protein oxidation processes, were
      significantly downregulated by Sqle knockdown. Taken together, our results
      suggest the molecular mechanism by which SNPs in the SQLE gene can affect meat
      quality.

PMID- 29196685
TI  - Medical examination powers miR-194-5p as a biomarker for postmenopausal
      osteoporosis.
AB  - An important attribute of microRNAs is their potential use as disease biomarkers.
      However, such applications may be restricted because of unsatisfactory
      performance of the microRNA of interest. Owing to moderate correlation with spine
      T-score, miR-194-5p was identified as a potential biomarker for postmenopausal
      osteoporosis. Here, we determined whether medical examination could improve its
      characteristic as a biomarker for postmenopausal osteoporosis. We recruited 230
      postmenopausal Chinese women to measure circulating levels of miR-194-5p,
      determine the spine bone status, and perform a 42-item medical examination. No
      obvious information redundancy was observed between miR-194-5p and any one item.
      However, on examining miR-194-5p alone, the sensitivity at fixed specificity of
      0.9 (SESP=0.9) was 0.27, implying poor identification of at-risk individuals.
      Model integration of the microRNA and multiple medical items strengthened this
      property; in addition, model complexity greatly contributed to performance
      improvement. Using a model composed of two artificial neural networks, the
      ability of miR-194-5p to identify at-risk individuals significantly improved
      (SESP=0.9 = 0.54) when correlated with five medical items: weight, age, left
      ventricular end systolic diameter, alanine aminotransferase, and urine epithelial
      cell count. We present a feasible way to achieve a more accurate microRNA-based
      biomarker for a disease of interest.

PMID- 29196686
TI  - Resting-state functional MRI reveals altered brain connectivity and its
      correlation with motor dysfunction in a mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative
      disorder, and no cure is available currently. Treatment of HD is likely to be
      most beneficial in the early, possibly pre-manifestation stage. The challenge is
      to determine the best time for intervention and evaluate putative efficacy in the
      absence of clinical symptoms. Resting-state functional MRI may represent a
      promising tool to develop biomarker reflecting early neuronal dysfunction in HD
      brain, because it can examine multiple brain networks without confounding effects
      of cognitive ability, which makes the resting-state fMRI promising as a
      translational bridge between preclinical study in animal models and clinical
      findings in HD patients. In this study, we examined brain regional connectivity
      and its correlation to brain atrophy, as well as motor function in the 18-week
      old N171-82Q HD mice. HD mice exhibited significantly altered functional
      connectivity in multiple networks. Particularly, the weaker intra-striatum
      connectivity was positively correlated with striatal atrophy, while striatum
      retrosplenial cortex connectivity is negatively correlated with striatal atrophy.
      The resting-state brain regional connectivity had no significant correlation with
      motor deficits in HD mice. Our results suggest that altered brain connectivity
      detected by resting-state fMRI might serve as an early disease biomarker in HD.

PMID- 29196687
TI  - 2.8 MUm emission and OH quenching analysis in Ho3+ doped fluorotellurite
      germanate glasses sensitized by Yb3+ and Er3.
AB  - The use of Yb3+ and Er3+ co-doping with Ho3+ to enhance and broaden the Ho3+: 5I6
      -> 5I7 ~2.8 MUm emissions are investigated in the fluorotellurite-germanate
      glasses. An intense ~3 MUm emission with a full width at half maximum (FWHM) of
      245 nm is achieved in the Er3+/Ho3+/Yb3+ triply-doped fluorotellurite-germanate
      glass upon excitation at 980 nm. The glass not only possesses considerably low OH
      absorption coefficient (0.189 cm-1), but also exhibits low phonon energy (704 cm
      1). Moreover, the measured lifetime of Ho3+: 5I6 level is as high as 0.218 ms. In
      addition, the energy transfer rate to hydroxyl groups and quantum efficiency
      (eta) of 5I6 level were calculated in detail by fitting the variations of
      lifetimes vs. the OH- concentrations. The formation ability and thermal stability
      of glasses have been improved by introducing GeO2 into fluorotellurite glasses.
      Results reveal that Er3+/Ho3+/Yb3+ triply-doped fluorotellurite-germanate glass
      is a potential kind of laser glass for efficient 3 MUm laser.

PMID- 29196688
TI  - Investigation of Atrial Vortices Using a Novel Right Heart Model and Possible
      Implications for Atrial Thrombus Formation.
AB  - The main aim of this paper is to characterize vortical flow structures in the
      healthy human right atrium, their impact on wall shear stresses and possible
      implications for atrial thrombus formation. 3D Particle Tracking Velocimetry is
      applied to a novel anatomically accurate compliant silicone right heart model to
      study the phase averaged and fluctuating flow velocity within the right atrium,
      inferior vena cava and superior vena cava under physiological conditions. We
      identify the development of two vortex rings in the bulk of the right atrium
      during the atrial filling phase leading to a rinsing effect at the atrial wall
      which break down during ventricular filling. We show that the vortex ring
      formation affects the hemodynamics of the atrial flow by a strong correlation
      (rho = 0.7) between the vortical structures and local wall shear stresses. Low
      wall shear stress regions are associated with absence of the coherent vortical
      structures which might be potential risk regions for atrial thrombus formation.
      We discuss possible implications for atrial thrombus formation in different
      regions of the right atrium.

PMID- 29196689
TI  - Impact of the crystal orientation of Fe-doped lithium niobate on photo-assisted
      proton exchange and chemical etching.
AB  - Photo-assisted proton-exchange (PAPE) is carried out on the +c- and y-surfaces of
      Fe-doped LiNbO3 crystals and the impact of the crystal orientation on the PAPE
      and the subsequent photo-assisted chemical etching (PACE) is investigated. The
      proton distributions and the morphologies of the proton-exchanged surfaces are
      studied by using Micro-FT-IR, Micro-Raman, optical and scanning electron
      microscopy. Through the PAPE process the proton-exchange can be confined in a
      specific region by an incident laser beam with fixed intensity profile. It is
      found that the y-surface is much more fragile than the +c-surface and that micro
      cracks are easily generated on the y-surface during the PAPE process. Moreover,
      the range and number of these micro-cracks can be controlled by the experimental
      parameters of the PAPE process. The etching morphology of the y-surface shows
      apparent directional features along the c-axis of LiNbO3 crystal and the proton
      spatial distribution is found elongated along the c-axis. Both effects are
      attributed to the accumulation of photovoltaic charges at the two sides of the
      illumination area along the c-axis.

PMID- 29196690
TI  - Fano resonances in bilayer graphene superlattices.
AB  - In this work, we address the ubiquitous phenomenon of Fano resonances in bilayer
      graphene. We consider that this phenomenon is as exotic as other phenomena in
      graphene because it can arise without an external extended states source or
      elaborate nano designs. However, there are not theoretical and/or experimental
      studies that report the impact of Fano resonances on the transport properties.
      Here, we carry out a systematic assessment of the contribution of the Fano
      resonances on the transport properties of bilayer graphene superlattices.
      Specifically, we find that by changing the number of periods, adjusting the
      barriers height as well as modifying the barriers and wells width it is possible
      to identify the contribution of Fano resonances on the conductance. Particularly,
      the coupling of Fano resonances with the intrinsic minibands of the superlattice
      gives rise to specific and identifiable changes in the conductance. Moreover, by
      reducing the angular range for the computation of the transport properties it is
      possible to obtain conductance curves with line-shapes quite similar to the Fano
      profile and the coupling profile between Fano resonance and miniband states. In
      fact, these conductance features could serve as unequivocal characteristic of the
      existence of Fano resonances in bilayer graphene.

PMID- 29196692
TI  - Advancement of magma fragmentation by inhomogeneous bubble distribution.
AB  - Decompression times reported in previous studies suggest that thoroughly brittle
      fragmentation is unlikely in actual explosive volcanic eruptions. What occurs in
      practice is brittle-like fragmentation, which is defined as the solid-like
      fracture of a material whose bulk rheological properties are close to those of a
      fluid. Through laboratory experiments and numerical simulation, the link between
      the inhomogeneous structure of bubbles and the development of cracks that may
      lead to brittle-like fragmentation was clearly demonstrated here. A rapid
      decompression test was conducted to simulate the fragmentation of a specimen
      whose pore morphology was revealed by X-ray microtomography. The dynamic response
      during decompression was observed by high-speed photography. Large variation was
      observed in the responses of the specimens even among specimens with equal bulk
      rheological properties. The stress fields of the specimens under decompression
      computed by finite element analysis shows that the presence of satellite bubbles
      beneath a large bubble induced the stress concentration. On the basis of the
      obtained results, a new mechanism for brittle-like fragmentation is proposed. In
      the proposed scenario, the second nucleation of bubbles near the fragmentation
      surface is an essential process for the advancement of fragmentation in an upward
      magma flow in a volcanic conduit.

PMID- 29196691
TI  - Evidence for single metal two electron oxidative addition and reductive
      elimination at uranium.
AB  - Reversible single-metal two-electron oxidative addition and reductive elimination
      are common fundamental reactions for transition metals that underpin major
      catalytic transformations. However, these reactions have never been observed
      together in the f-block because these metals exhibit irreversible one- or multi
      electron oxidation or reduction reactions. Here we report that azobenzene
      oxidises sterically and electronically unsaturated uranium(III) complexes to
      afford a uranium(V)-imido complex in a reaction that satisfies all criteria of a
      single-metal two-electron oxidative addition. Thermolysis of this complex
      promotes extrusion of azobenzene, where H-/D-isotopic labelling finds no
      isotopomer cross-over and the non-reactivity of a nitrene-trap suggests that
      nitrenes are not generated and thus a reductive elimination has occurred. Though
      not optimally balanced in this case, this work presents evidence that classical d
      block redox chemistry can be performed reversibly by f-block metals, and that
      uranium can thus mimic elementary transition metal reactivity, which may lead to
      the discovery of new f-block catalysis.

PMID- 29196693
TI  - Relationship between erectile dysfunction and the neutrophil to lymphocyte and
      platelet to lymphocyte ratios.
AB  - The most important cause of erectile dysfunction (ED) among aging men is organic
      disease due to vascular disturbance that is often caused by atherosclerosis.
      Recently, studies have shown that atherosclerosis can manifest as an active
      inflammatory process rather than as passive vascular injury caused by lipid
      infiltration. Our study aimed to examine the association of ED with the
      neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR), both
      of which are markers of inflammation. Between December 2014 and May 2015, 101
      male patients aged 40-70 years who were seen at our institute due to ED were
      included in this study. Thirty-one sexually active men with similar clinical and
      demographic characteristics without ED were included in our study as a control
      group. The control and patient groups were compared with respect to their NLR and
      PLR values as well as other hormonal, biochemical, hematological parameters. The
      median ages of the patient and control groups were 49 (40-69) and 48 (43-65)
      years old, respectively. Comorbidities such as hypertension, diabetes, chronic
      obstructive pulmonary disease (COPD), and coronary artery disease were not
      significantly different between the groups (p > 0.05). The neutrophil-to
      lymphocyte and platelet-to-lymphocyte ratios were significantly higher in the
      patient group than in the control group (p < 0.05). Furthermore, the detected CRP
      levels were also significantly higher in the patient group than in the control
      group (p < 0.001). In the correlation analysis, the NLR, PLR, and CRP levels were
      negatively correlated with the IIEF-5 scores. A multivariate analysis was
      performed to determine the independent predictors of ED. PLR was identified as an
      independent predictor for ED. The neutrophil-to-lymphocyte and especially
      platelet-to-lymphocyte ratios are correlated with a diagnosis of ED, and these
      ratios could serve as practical parameters that will not elicit additional costs.

PMID- 29196694
TI  - Latent tuberculosis infection among patients with erectile dysfunction.
AB  - No previous studies have investigated the prevalence of latent tuberculosis
      infection (LTBI) among patients with erectile dysfunction (ED) or its
      contribution to the development of high-grade ED through a process of chronic
      inflammation-induced atherosclerosis. The aim of this study was to determine the
      frequency of LTBI among patients with erectile dysfunction and to explore the
      contribution of LTBI to high-grade ED. For all the study sample, clinical
      evaluation, imaging studies, and laboratory investigations were provided.
      Evaluation included, but was not confined to, scrotal ultrasonography, tuberculin
      skin test, and QuantiFERON-TB Gold test. The study sample mean +/- SD age was
      47.9 +/- 13.6 years. Approximately 30% of the patients had LTBI and 43% had high
      grade ED. After a multivariate analysis, it was found that older age (>=40 years)
      (OR, 5.2; 95% CI, 1.9-54.6; p 0.004), metabolic syndrome (MS) (OR, 3.4; 95% CI,
      1.3-48.2; p 0.016), and LTBI (OR, 4.1; 95% CI, 1.7-61.3; p 0.021) were
      significantly, independently associated with high-grade ED as opposed to low
      grade ED. In conclusion, the prevalence of LTBI among patients with high-grade ED
      is higher than among those with low-grade ED. In addition to LTBI, older age and
      MS are associated with high-grade ED as opposed to low-grade ED.

PMID- 29196695
TI  - Legume crop rotation suppressed nitrifying microbial community in a sugarcane
      cropping soil.
AB  - Nitrifying microorganisms play an important role in nitrogen (N) cycling in
      agricultural soils as nitrification leads to accumulation of nitrate (NO3-) that
      is readily lost through leaching and denitrification, particularly in high
      rainfall regions. Legume crop rotation in sugarcane farming systems can suppress
      soil pathogens and improve soil health, but its effects on soil nitrifying
      microorganisms are not well understood. Using shotgun metagenomic sequencing, we
      investigated the impact of two legume break crops, peanut (Arachis hypogaea) and
      soybean (Glycine max), on the nitrifying communities in a sugarcane cropping
      soil. Cropping with either legume substantially increased abundances of soil
      bacteria and archaea and altered the microbial community composition, but did not
      significantly alter species richness and evenness relative to a bare fallow
      treatment. The ammonia oxidisers were mostly archaeal rather than bacterial, and
      were 24-44% less abundant in the legume cropping soils compared to the bare
      fallow. Furthermore, abundances of the archaeal amoA gene encoding ammonia
      monooxygenase in the soybean and peanut cropping soils were only 30-35% of that
      in the bare fallow. These results warrant further investigation into the
      mechanisms driving responses of ammonia oxidising communities and their
      nitrification capacity in soil during legume cropping.

PMID- 29196696
TI  - Author Correction: The efficacy and toxicities of intensive induction
      chemotherapy followed by concurrent chemoradiotherapy in nasopharyngeal carcinoma
      patients with N3 disease.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29196697
TI  - De novo transcriptome assembly of Zanthoxylum bungeanum using Illumina sequencing
      for evolutionary analysis and simple sequence repeat marker development.
AB  - Zanthoxylum, an ancient economic crop in Asia, has a satisfying aromatic taste
      and immense medicinal values. A lack of genomic information and genetic markers
      has limited the evolutionary analysis and genetic improvement of Zanthoxylum
      species and their close relatives. To better understand the evolution,
      domestication, and divergence of Zanthoxylum, we present a de novo transcriptome
      analysis of an elite cultivar of Z. bungeanum using Illumina sequencing; we then
      developed simple sequence repeat markers for identification of Zanthoxylum. In
      total, we predicted 45,057 unigenes and 22,212 protein coding sequences,
      approximately 90% of which showed significant similarities to known proteins in
      databases. Phylogenetic analysis indicated that Zanthoxylum is relatively recent
      and estimated to have diverged from Citrus ca. 36.5-37.7 million years ago. We
      also detected a whole-genome duplication event in Zanthoxylum that occurred 14
      million years ago. We found no protein coding sequences that were significantly
      under positive selection by Ka/Ks. Simple sequence repeat analysis divided 31
      Zanthoxylum cultivars and landraces into three major groups. This Zanthoxylum
      reference transcriptome provides crucial information for the evolutionary study
      of the Zanthoxylum genus and the Rutaceae family, and facilitates the
      establishment of more effective Zanthoxylum breeding programs.

PMID- 29196698
TI  - High-pressure versus low-pressure home non-invasive positive pressure ventilation
      with built-in software in patients with stable hypercapnic COPD: a pilot study.
AB  - High-pressure non-invasive positive pressure ventilation (NPPV) is a new strategy
      targeted at maximally reducing arterial carbon dioxide. However, high inspiratory
      positive airway pressure (IPAP) might cause respiratory adverse events likely to
      diminish the benefit of NPPV. In the setting of ventilatory support, monitoring
      NPPV efficacy and resolving problems promptly are critical. This study assessed
      the treatment effect of high and low-pressure NPPV in chronic hypercapnic COPD
      using home ventilator with built-in software. In this pilot study, we
      investigated 34 patients using NPPV for 3 months. 13 patients used high-pressure
      ventilation and 21 patients used low-pressure ventilation. The primary outcome
      was daytime partial pressure of arterial blood carbon dioxide (PaCO2). There were
      no between-group differences in daytime PaCO2 and FEV1, but a trend favouring
      high-pressure NPPV was observed. Significant between-group differences were found
      in the transition dyspnoea index (TDI) (high-pressure, 1.69 +/- 1.75, versus low
      pressure, -0.04 +/- 2.71, p = 0.044). No differences were found in usage time,
      leakage, health-related quality of life, spirometry, or 6-minute walk test. High
      pressure NPPV with built-in software monitoring in patients with chronic
      hypercapnic COPD is associated with improvement in TDI scores and a positive
      trend in favour of high-pressure NPPV for improving PaCO2 is observed.

PMID- 29196700
TI  - Thermally nucleated magnetic reversal in CoFeB/MgO nanodots.
AB  - Power consumption is the main limitation in the development of new high
      performance random access memory for portable electronic devices. Magnetic RAM
      (MRAM) with CoFeB/MgO based magnetic tunnel junctions (MTJs) is a promising
      candidate for reducing the power consumption given its non-volatile nature while
      achieving high performance. The dynamic properties and switching mechanisms of
      MTJs are critical to understanding device operation and to enable scaling of
      devices below 30 nm in diameter. Here we show that the magnetic reversal
      mechanism is incoherent and that the switching is thermally nucleated at device
      operating temperatures. Moreover, we find an intrinsic thermal switching field
      distribution arising on the sub-nanosecond time-scale even in the absence of size
      and anisotropy distributions or material defects. These features represent the
      characteristic signature of the dynamic properties in MTJs and give an intrinsic
      limit to reversal reliability in small magnetic nanodevices.

PMID- 29196699
TI  - Altered resting-state brain activity in Parkinson's disease patients with
      freezing of gait.
AB  - Freezing of gait (FOG) is a common and debilitating symptom in Parkinson's
      disease (PD). The current study investigated alterations of resting-state
      spontaneous brain activity in PD patients with FOG. A total of 29 patients with
      FOG, 28 patients without FOG and 31 controls were included. All subjects
      underwent resting-state functional MRI, and the amplitude of low-frequency
      fluctuation (ALFF) was calculated to measure the spontaneous brain activity.
      Between-group differences and correlations with FOG severity (both subjective and
      objective measures) were analyzed. Compared to those without FOG, patients with
      FOG showed increased ALFF in right anterior cingulate cortex (ACC) and left
      inferior parietal lobule (IPL), as well as decreased ALFF in right superior
      frontal gyrus (SFG), bilateral cerebellum and left thalamus. Correlation analyses
      demonstrated that ALFF within the right SFG, right ACC and bilateral pallidum
      were positively correlated with FOG; while ALFF within the thalamus, putamen,
      cerebellum and sensorimotor regions were negatively correlated. Our results
      indicate that FOG is associated with dysfunction within frontal-parietal regions,
      along with increased inhibitory outputs from basal ganglia. Additionally, altered
      activity of cerebellum implicates its role in the pathophysiology of FOG. These
      findings provide further insight into the underlying neural mechanisms of FOG in
      PD patients.

PMID- 29196701
TI  - The repeat region of cortactin is intrinsically disordered in solution.
AB  - The multi-domain protein, cortactin, contains a 37-residue repeating motif that
      binds to actin filaments. This cortactin repeat region comprises 61/2 similar
      copies of the motif and binds actin filaments. To better understand this region
      of cortactin, and its fold, we conducted extensive biophysical analysis. Size
      exclusion chromatography with multi-angle light scattering (SEC-MALS) reveals
      that neither constructs of the cortactin repeats alone or together with the
      adjacent helical region homo-oligomerize. Using circular dichroism (CD) we find
      that in solution the cortactin repeats resemble a coil-like intrinsically
      disordered protein. Small-angle X-ray scattering (SAXS) also indicates that the
      cortactin repeats are intrinsically unfolded, and the experimentally observed
      radius of gyration (R g) is coincidental to that calculated by the program
      Flexible-Meccano for an unfolded peptide of this length. Finally, hydrogen
      deuterium exchange mass spectrometry (HDX-MS) indicates that the domain contains
      limited hydrophobic core regions. These experiments therefore provide evidence
      that in solution the cortactin repeat region of cortactin is intrinsically
      disordered.

PMID- 29196702
TI  - Spatial statistical modelling of capillary non-perfusion in the retina.
AB  - Manual grading of lesions in retinal images is relevant to clinical management
      and clinical trials, but it is time-consuming and expensive. Furthermore, it
      collects only limited information - such as lesion size or frequency. The spatial
      distribution of lesions is ignored, even though it may contribute to the overall
      clinical assessment of disease severity, and correspond to microvascular and
      physiological topography. Capillary non-perfusion (CNP) lesions are central to
      the pathogenesis of major causes of vision loss. Here we propose a novel method
      to analyse CNP using spatial statistical modelling. This quantifies the
      percentage of CNP-pixels in each of 48 sectors and then characterises the spatial
      distribution with goniometric functions. We applied our spatial approach to a set
      of images from patients with malarial retinopathy, and found it compares
      favourably with the raw percentage of CNP-pixels and also with manual grading.
      Furthermore, we were able to quantify a biological characteristic of macular CNP
      in malaria that had previously only been described subjectively: clustering at
      the temporal raphe. Microvascular location is likely to be biologically relevant
      to many diseases, and so our spatial approach may be applicable to a diverse
      range of pathological features in the retina and other organs.

PMID- 29196703
TI  - Induction of auxin biosynthesis and WOX5 repression mediate changes in root
      development in Arabidopsis exposed to chitosan.
AB  - Chitosan is a natural polymer with applications in agriculture, which causes
      plasma membrane permeabilisation and induction of intracellular reactive oxygen
      species (ROS) in plants. Chitosan has been mostly applied in the phylloplane to
      control plant diseases and to enhance plant defences, but has also been
      considered for controlling root pests. However, the effect of chitosan on roots
      is virtually unknown. In this work, we show that chitosan interfered with auxin
      homeostasis in Arabidopsis roots, promoting a 2-3 fold accumulation of indole
      acetic acid (IAA). We observed chitosan dose-dependent alterations of auxin
      synthesis, transport and signalling in Arabidopsis roots. As a consequence, high
      doses of chitosan reduce WOX5 expression in the root apical meristem and arrest
      root growth. Chitosan also propitiates accumulation of salicylic (SA) and
      jasmonic (JA) acids in Arabidopsis roots by induction of genes involved in their
      biosynthesis and signalling. In addition, high-dose chitosan irrigation of tomato
      and barley plants also arrests root development. Tomato root apices treated with
      chitosan showed isodiametric cells respect to rectangular cells in the controls.
      We found that chitosan causes strong alterations in root cell morphology. Our
      results highlight the importance of considering chitosan dose during agronomical
      applications to the rhizosphere.

PMID- 29196704
TI  - Repurposing a photosynthetic antenna protein as a super-resolution microscopy
      label.
AB  - Techniques such as Stochastic Optical Reconstruction Microscopy (STORM) and
      Structured Illumination Microscopy (SIM) have increased the achievable resolution
      of optical imaging, but few fluorescent proteins are suitable for super
      resolution microscopy, particularly in the far-red and near-infrared emission
      range. Here we demonstrate the applicability of CpcA, a subunit of the
      photosynthetic antenna complex in cyanobacteria, for STORM and SIM imaging. The
      periodicity and width of fabricated nanoarrays of CpcA, with a covalently
      attached phycoerythrobilin (PEB) or phycocyanobilin (PCB) chromophore, matched
      the lines in reconstructed STORM images. SIM and STORM reconstructions of
      Escherichia coli cells harbouring CpcA-labelled cytochrome bd 1 ubiquinol oxidase
      in the cytoplasmic membrane show that CpcA-PEB and CpcA-PCB are suitable for
      super-resolution imaging in vivo. The stability, ease of production, small size
      and brightness of CpcA-PEB and CpcA-PCB demonstrate the potential of this largely
      unexplored protein family as novel probes for super-resolution microscopy.

PMID- 29196705
TI  - Energetic instability of passive states in thermodynamics.
AB  - Passivity is a fundamental concept in thermodynamics that demands a quantum
      system's energy cannot be lowered by any reversible, unitary process acting on
      the system. In the limit of many such systems, passivity leads in turn to the
      concept of complete passivity, thermal states and the emergence of a
      thermodynamic temperature. Here we only consider a single system and show that
      every passive state except the thermal state is unstable under a weaker form of
      reversibility. Indeed, we show that given a single copy of any athermal quantum
      state, an optimal amount of energy can be extracted from it when we utilise a
      machine that operates in a reversible cycle. This means that for individual
      systems, the only form of passivity that is stable under general reversible
      processes is complete passivity, and thus provides a physically motivated
      identification of thermal states when we are not operating in the thermodynamic
      limit.

PMID- 29196706
TI  - MALDI mass spectrometry imaging of erlotinib administered in combination with
      bevacizumab in xenograft mice bearing B901L, EGFR-mutated NSCLC cells.
AB  - Combination therapy of erlotinib plus bevacizumab improves progression-free
      survival of patients with epidermal growth factor receptor-mutated (EGFR-mutated)
      advanced non-small-cell lung cancer (NSCLC) compared with erlotinib alone.
      Although improved delivery and distribution of erlotinib to tumours as a result
      of the normalization of microvessels by bevacizumab is thought to be one of the
      underlying mechanisms, there is insufficient supporting evidence. B901L cells
      derived from EGFR-mutated NSCLC were subcutaneously implanted into mice, and mice
      were treated with bevacizumab or human IgG followed by treatment with erlotinib.
      The distribution of erlotinib in their tumours at different times after erlotinib
      administration was analysed by matrix-assisted laser desorption/ionization mass
      spectrometry imaging (MALDI MSI). We also analysed the distribution of erlotinib
      metabolites and the distribution of erlotinib in tumours refractory to erlotinib,
      which were established by long-term treatment with erlotinib. We found that
      erlotinib was broadly diffused in the tumours from B901L-implanted xenograft
      mice, independently of bevacizumab treatment. We also found that erlotinib
      metabolites were co-localized with erlotinib and that erlotinib in erlotinib
      refractory tumours was broadly distributed throughout the tumour tissue.
      Multivariate imaging approaches using MALDI MSI as applied in this study are of
      great value for pharmacokinetic studies in drug development.

PMID- 29196707
TI  - Crumbs, Moesin and Yurt regulate junctional stability and dynamics for a proper
      morphogenesis of the Drosophila pupal wing epithelium.
AB  - The Crumbs (Crb) complex is a key epithelial determinant. To understand its role
      in morphogenesis, we examined its function in the Drosophila pupal wing, an
      epithelium undergoing hexagonal packing and formation of planar-oriented hairs.
      Crb distribution is dynamic, being stabilized to the subapical region just before
      hair formation. Lack of crb or stardust, but not DPatj, affects hexagonal packing
      and delays hair formation, without impairing epithelial polarities but with
      increased fluctuations in cell junctions and perimeter length, fragmentation of
      adherens junctions and the actomyosin cytoskeleton. Crb interacts with Moesin and
      Yurt, FERM proteins regulating the actomyosin network. We found that Moesin and
      Yurt distribution at the subapical region depends on Crb. In contrast to previous
      reports, yurt, but not moesin, mutants phenocopy crb junctional defects.
      Moreover, while unaffected in crb mutants, cell perimeter increases in yurt
      mutant cells and decreases in the absence of moesin function. Our data suggest
      that Crb coordinates proper hexagonal packing and hair formation, by modulating
      junction integrity via Yurt and stabilizing cell perimeter via both Yurt and
      Moesin. The Drosophila pupal wing thus appears as a useful system to investigate
      the functional diversification of the Crb complex during morphogenesis,
      independently of its role in polarity.

PMID- 29196708
TI  - The serine proteinase hepsin is an activator of pro-matrix metalloproteinases:
      molecular mechanisms and implications for extracellular matrix turnover.
AB  - Increasing evidence implicates serine proteinases in the proteolytic cascades
      leading to the pathological destruction of extracellular matrices such as
      cartilage in osteoarthritis (OA). We have previously demonstrated that the type
      II transmembrane serine proteinase (TTSP) matriptase acts as a novel initiator of
      cartilage destruction via the induction and activation of matrix
      metalloproteinases (MMPs). Hepsin is another TTSP expressed in OA cartilage such
      that we hypothesized this proteinase may also contribute to matrix turnover.
      Herein, we demonstrate that addition of hepsin to OA cartilage in explant culture
      induced significant collagen and aggrecan release and activated proMMP-1 and
      proMMP-3. Furthermore, hepsin directly cleaved the aggrecan core protein at a
      novel cleavage site within the interglobular domain. Hepsin expression correlated
      with synovitis as well as tumour necrosis factor alpha expression, and was
      induced in cartilage by a pro-inflammatory stimulus. However, a major difference
      compared to matriptase was that hepsin demonstrated markedly reduced capacity to
      activate proteinase-activated receptor-2. Overall, our data suggest that hepsin,
      like matriptase, induces potent destruction of the extracellular matrix whilst
      displaying distinct efficiencies for the cleavage of specific substrates.

PMID- 29196709
TI  - Lck is a relevant target in chronic lymphocytic leukaemia cells whose expression
      variance is unrelated to disease outcome.
AB  - Pathogenesis of chronic lymphocytic leukaemia (CLL) is contingent upon antigen
      receptor (BCR) expressed by malignant cells of this disease. Studies on somatic
      hypermutation of the antigen binding region, receptor expression levels and
      signal capacity have all linked BCR on CLL cells to disease prognosis. Our
      previous work showed that the src-family kinase Lck is a targetable mediator of
      BCR signalling in CLL cells, and that variance in Lck expression associated with
      ability of BCR to induce signal upon engagement. This latter finding makes Lck
      similar to ZAP70, another T-cell kinase whose aberrant expression in CLL cells
      also associates with BCR signalling capacity, but also different because ZAP70 is
      not easily pharmacologically targetable. Here we describe a robust method of
      measuring Lck expression in CLL cells using flow cytometry. However, unlike ZAP70
      whose expression in CLL cells predicts prognosis, we find Lck expression and
      disease outcome in CLL are unrelated despite observations that its inhibition
      produces effects that biologically resemble the egress phenotype taken on by CLL
      cells treated with idelalisib. Taken together, our findings provide insight into
      the pathobiology of CLL to suggest a more complex relationship between expression
      of molecules within the BCR signalling pathway and disease outcome.

PMID- 29196710
TI  - Molecular Identification of ten species of stored-product psocids through
      microarray method based on ITS2 rDNA.
AB  - Stored-product psocids (Psocoptera: Liposcelididae) are cosmopolitan storage
      pests that can damage stored products and cause serious economic loss. However,
      because of the body size (~1 mm) of eggs, nymphs, and adults, morphological
      identification of most stored-product psocids is difficult and hampers effective
      identification. In this study, 10 economically important stored-product
      Liposcelis spp. psocids (Liposcelis brunnea, L. entomophila, L. decolor, L.
      pearmani, L. rufa, L.mendax, L. bostrychophila, L. corrodens, L. paeta, and L.
      tricolor) were collected from 25 geographic locations in 3 countries (China,
      Czech Republic, and the United States). Ten species-specific probes for
      identifying these 10 psocid species were designed based on ITS2 sequences. The
      microarray method and reaction system were optimized. Specificity of each of the
      ten probes was tested, and all probes were found suitable for use in
      identification of the respective10 Liposcelis spp. psocids at 66  degrees C. This
      method was also used to identify an unknown psocid species collected in Taian,
      China. This work has contributed to the development of a molecular identification
      method for stored-product psocids, and can provide technical support not only to
      facilitate identification of intercepted samples in relation to plant quarantine,
      but also for use in insect pest monitoring.

PMID- 29196711
TI  - The Uniform Pattern of Growth and Skeletal Maturation during the Human Adolescent
      Growth Spurt.
AB  - Humans are one of the few species undergoing an adolescent growth spurt. Because
      children enter the spurt at different ages making age a poor maturity measure,
      longitudinal studies are necessary to identify the growth patterns and identify
      commonalities in adolescent growth. The standard maturity determinant, peak
      height velocity (PHV) timing, is difficult to estimate in individuals due to
      diurnal, postural, and measurement variation. Using prospective longitudinal
      populations of healthy children from two North American populations, we compared
      the timing of the adolescent growth spurt's peak height velocity to normalized
      heights and hand skeletal maturity radiographs. We found that in healthy
      children, the adolescent growth spurt is standardized at 90% of final height with
      similar patterns for children of both sexes beginning at the initiation of the
      growth spurt. Once children enter the growth spurt, their growth pattern is
      consistent between children with peak growth at 90% of final height and skeletal
      maturity closely reflecting growth remaining. This ability to use 90% of final
      height as easily identified important maturity standard with its close
      relationship to skeletal maturity represents a significant advance allowing
      accurate prediction of future growth for individual children and accurate
      maturity comparisons for future studies of children's growth.

PMID- 29196712
TI  - Effects of neuroactive agents on axonal growth and pathfinding of retinal
      ganglion cells generated from human stem cells.
AB  - We recently established a novel method for generating functional human retinal
      ganglion cells (RGCs) from human induced pluripotent cells (hiPSCs). Here, we
      confirmed that RGCs can also be generated from human embryonic stem cells
      (hESCs). We investigated the usefulness of human RGCs with long axons for
      assessing the effects of chemical agents, such as the neurotrophic factor, nerve
      growth factor (NGF), and the chemorepellent factors, semaphorin 3 A (SEMA3A) and
      SLIT1. The effects of direct and local administration of each agent on axonal
      projection were evaluated by immunohistochemistry, real-time polymerase chain
      reaction (PCR), and real-time imaging, in which the filopodia of the growth cone
      served as an excellent marker. A locally sustained agent system showed that the
      axons elongate towards NGF, but were repelled by SEMA3A and SLIT1. Focally
      transplanted beads that released SLIT1 bent the pathfinding of axons, imitating
      normal retinal development. Our innovative system for assessing the effects of
      chemical compounds using human RGCs may facilitate development of novel drugs for
      the examination, prophylaxis, and treatment of diseases. It may also be useful
      for observing the physiology of the optic nerve in vitro, which might lead to
      significant progress in the science of human RGCs.

PMID- 29196713
TI  - A hybrid strain and thermal energy harvester based on an infra-red sensitive Er3+
      modified poly(vinylidene fluoride) ferroelectret structure.
AB  - In this paper, a novel infra-red (IR) sensitive Er3+ modified poly(vinylidene
      fluoride) (PVDF) (Er-PVDF) film is developed for converting both mechanical and
      thermal energies into useful electrical power. The addition of Er3+ to PVDF is
      shown to improve piezoelectric properties due to the formation of a self
      polarized ferroelectric beta-phase and the creation of an electret-like porous
      structure. In addition, we demonstrate that Er3+ acts to enhance heat transfer
      into the Er-PVDF film due to its excellent infrared absorbance, which, leads to
      rapid and large temperature fluctuations and improved pyroelectric energy
      transformation. We demonstrate the potential of this novel material for
      mechanical energy harvesting by creating a durable ferroelectret energy
      harvester/nanogenerator (FTNG). The high thermal stability of the beta-phase
      enables the FTNG to harvest large temperature fluctuations (DeltaT ~ 24 K).
      Moreover, the superior mechanosensitivity, SM ~ 3.4 VPa-1 of the FTNG enables the
      design of a wearable self-powered health-care monitoring system by human-machine
      integration. The combination of rare-earth ion, Er3+ with the ferroelectricity of
      PVDF provides a new and robust approach for delivering smart materials and
      structures for self-powered wireless technologies, sensors and Internet of Things
      (IoT) devices.

PMID- 29196714
TI  - Screening and identification of lncRNAs as potential biomarkers for pulmonary
      tuberculosis.
AB  - Pulmonary tuberculosis (TB) is among the diseases with the highest morbidity and
      mortality worldwide. Effective diagnostic methods for TB are lacking. In this
      study, we investigated long non-coding RNAs (lncRNAs) in plasma using microarray
      and the potential diagnostic value of lncRNAs for TB. We found a total of 163 up
      regulated lncRNAs and 348 down-regulated lncRNAs. Gene ontology (GO), Kyoto
      Encyclopedia of Genes and Genomes (KEGG) and coding-noncoding co-expression (CNC)
      analyses showed that functions of differentially expressed lncRNAs were mainly
      enriched in the regulation of alpha-beta T cell activation and the T cell
      receptor signalling pathway. Four differentially expressed lncRNAs, NR_038221
      (fold change = 3.79, P < 0.01), NR_003142 (fold change = 1.69, P < 0.05),
      ENST00000570366 (fold change = 3.04, P < 0.05), and ENST00000422183 (fold change
      = 2.11, P < 0.001), were verified using RT-qPCR. Among those, NR_038221,
      NR_003142, and ENST00000570366 were found to be up-regulated, while
      ENST00000422183 was down-regulated. The value of the area under the curve (AUC)
      for the diagnostic model consisting of the four lncRNAs was 0.845 (sensitivity =
      79.2%, specificity = 75%). We further predicted 85 mRNAs and 404 miRNAs that
      potentially interact with these lncRNAs. Our study revealed the potential value
      of lncRNAs as biomarkers for early diagnosis of TB and the underlying mechanisms
      of these abnormally expressed lncRNAs in the pathogenesis of TB.

PMID- 29196715
TI  - Optimization of segmented thermoelectric generator using Taguchi and ANOVA
      techniques.
AB  - Recent studies have demonstrated that segmented thermoelectric generators (TEGs)
      can operate over large thermal gradient and thus provide better performance
      (reported efficiency up to 11%) as compared to traditional TEGs, comprising of
      single thermoelectric (TE) material. However, segmented TEGs are still in early
      stages of development due to the inherent complexity in their design optimization
      and manufacturability. In this study, we demonstrate physics based numerical
      techniques along with Analysis of variance (ANOVA) and Taguchi optimization
      method for optimizing the performance of segmented TEGs. We have considered
      comprehensive set of design parameters, such as geometrical dimensions of p-n
      legs, height of segmentation, hot-side temperature, and load resistance, in order
      to optimize output power and efficiency of segmented TEGs. Using the state-of-the
      art TE material properties and appropriate statistical tools, we provide near
      optimum TEG configuration with only 25 experiments as compared to 3125
      experiments needed by the conventional optimization methods. The effect of
      environmental factors on the optimization of segmented TEGs is also studied.
      Taguchi results are validated against the results obtained using traditional full
      factorial optimization technique and a TEG configuration for simultaneous
      optimization of power and efficiency is obtained.

PMID- 29196716
TI  - Disrupted superior collicular activity may reveal cervical dystonia disease
      pathomechanisms.
AB  - Cervical dystonia is a common neurological movement disorder characterised by
      muscle contractions causing abnormal movements and postures affecting the head
      and neck. The neural networks underpinning this condition are incompletely
      understood. While animal models suggest a role for the superior colliculus in its
      pathophysiology, this link has yet to be established in humans. The present
      experiment was designed to test the hypothesis that disrupted superior collicular
      processing is evident in affected patients and in relatives harbouring a disease
      specific endophenotype (abnormal temporal discrimination). The study participants
      were 16 cervical dystonia patients, 16 unaffected first-degree relatives with
      abnormal temporal discrimination, 16 unaffected first-degree relatives with
      normal temporal discrimination and 16 healthy controls. The response of
      participant's superior colliculi to looming stimuli was assessed by functional
      magnetic resonance imaging. Cervical dystonia patients and relatives with
      abnormal temporal discrimination demonstrated (i) significantly reduced superior
      collicular activation for whole brain and region of interest analysis; (ii) a
      statistically significant negative correlation between temporal discrimination
      threshold and superior collicular peak values. Our results support the hypothesis
      that disrupted superior collicular processing is involved in the pathogenesis of
      cervical dystonia. These findings, which align with animal models of cervical
      dystonia, shed new light on pathomechanisms in humans.

PMID- 29196717
TI  - Culturomics and Amplicon-based Metagenomic Approaches for the Study of Fungal
      Population in Human Gut Microbiota.
AB  - Herein, the mycobiota was characterized in fecal samples from sick patients and
      healthy subjects, collected from different geographical locations and using both
      culturomics and amplicon-based metagenomics approaches. Using the culturomics
      approach, a total of 17,800 fungal colonies were isolated from 14 fecal samples,
      and resulted in the isolation of 41 fungal species, of which 10 species had not
      been previously reported in the human gut. Deep sequencing of fungal-directed
      ITS1 and ITS2 amplicons led to the detection of a total of 142 OTUs and 173 OTUs
      from the ITS1 and ITS2 regions, respectively. Ascomycota composed the largest
      fraction of the total OTUs analyzed (78.9% and 68.2% of the OTUs from the ITS1
      and ITS2 regions, respectively), followed by Basidiomycota (16.9% and 30.1% of
      the OTUs from the ITS1 and ITS2 regions, respectively). Interestingly, the
      results demonstrate that the ITS1/ITS2 amplicon sequencing provides different
      information about gut fungal communities compared to culturomics, though both
      approaches complete each other in assessing fungal diversity in fecal samples. We
      also report higher fungal diversity and abundance in patients compared to healthy
      subjects. In conclusion, combining both culturomic and amplicon-based metagenomic
      approaches may be a novel strategy towards analyzing fungal compositions in the
      human gut.

PMID- 29196719
TI  - Publisher Correction: Efficient ECG Compression and QRS Detection for E-Health
      Applications.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29196720
TI  - Addition of a histone deacetylase inhibitor increases recombinant protein
      expression in Medicago truncatula cell cultures.
AB  - Plant cell cultures are an attractive platform for the production of recombinant
      proteins. A major drawback, hindering the establishment of plant cell suspensions
      as an industrial platform, is the low product yield obtained thus far. Histone
      acetylation is associated with increased transcription levels, therefore it is
      expected that the use of histone deacetylase inhibitors would result in an
      increase in mRNA and protein levels. Here, this hypothesis was tested by adding a
      histone deacetylase inhibitor, suberanilohydroxamic acid (SAHA), to a cell line
      of the model legume Medicago truncatula expressing a recombinant human protein.
      Histone deacetylase inhibition by SAHA and histone acetylation levels were
      studied, and the effect of SAHA on gene expression and recombinant protein levels
      was assessed by digital PCR. SAHA addition effectively inhibited histone
      deacetylase activity resulting in increased histone acetylation. Higher levels of
      transgene expression and accumulation of the associated protein were observed.
      This is the first report describing histone deacetylase inhibitors as inducers of
      recombinant protein expression in plant cell suspensions as well as the use of
      digital PCR in these biological systems. This study paves the way for employing
      epigenetic strategies to improve the final yields of recombinant proteins
      produced by plant cell cultures.

PMID- 29196721
TI  - On the effect of low oxygen concentrations on bacterial degradation of sinking
      particles.
AB  - In marine oxygen (O2) minimum zones (OMZs), the transfer of particulate organic
      carbon (POC) to depth via the biological carbon pump might be enhanced as a
      result of slower remineralisation under lower dissolved O2 concentrations (DO).
      In parallel, nitrogen (N) loss to the atmosphere through microbial processes,
      such as denitrification and anammox, is directly linked to particulate nitrogen
      (PN) export. However it is unclear (1) whether DO is the only factor that
      potentially enhances POC transfer in OMZs, and (2) if particle fluxes are
      sufficient to support observed N loss rates. We performed a degradation
      experiment on sinking particles collected from the Baltic Sea, where anoxic zones
      are observed. Sinking material was harvested using surface-tethered sediment
      traps and subsequently incubated in darkness at different DO levels, including
      severe suboxia (<0.5 mg l-1 DO). Our results show that DO plays a role in
      regulating POC and PN degradation rates. POC(PN) degradation was reduced by
      approximately 100% from the high to low DO to the lowest DO. The amount of NH4+
      produced from the pool of remineralising organic N matched estimations of NH4+
      anammox requirements during our experiment. This anammox was likely fueled by DON
      degradation rather than PON degradation.

PMID- 29196718
TI  - The role of the systemic inflammatory response in predicting outcomes in patients
      with operable cancer: Systematic review and meta-analysis.
AB  - Cancer remains a leading causes of death worldwide and an elevated systemic
      inflammatory response (SIR) is associated with reduced survival in patients with
      operable cancer. This review aims to examine the evidence for the role of
      systemic inflammation based prognostic scores in patients with operable cancers.
      A wide-ranging literature review using targeted medical subject headings for
      human studies in English was carried out in the MEDLINE, EMBASE, and CDSR
      databases until the end of 2016. The SIR has independent prognostic value, across
      tumour types and geographical locations. In particular neutrophil lymphocyte
      ratio (NLR) (n = 158), platelet lymphocyte ratio (PLR) (n = 68), lymphocyte
      monocyte ratio (LMR) (n = 21) and Glasgow Prognostic Score/ modified Glasgow
      Prognostic Score (GPS/mGPS) (n = 60) were consistently validated. On meta
      analysis there was a significant relationship between elevated NLR and overall
      survival (OS) (p < 0.00001)/ cancer specific survival (CSS) (p < 0.00001),
      between elevated LMR and OS (p < 0.00001)/CSS (p < 0.00001), and elevated PLR and
      OS (p < 0.00001)/CSS (p = 0.005). There was also a significant relationship
      between elevated GPS/mGPS and OS (p < 0.00001)/CSS (p < 0.00001). These results
      consolidate the prognostic value of the NLR, PLR, LMR and GPS/mGPS in patients
      with resectable cancers. This is particularly true for the NLR/GPS/mGPS which
      should form part of the routine preoperative and postoperative workup.

PMID- 29196722
TI  - Abstract spatial, but not body-related, visual information guides bimanual
      coordination.
AB  - Visual spatial information is paramount in guiding bimanual coordination, but
      anatomical factors, too, modulate performance in bimanual tasks. Vision conveys
      not only abstract spatial information, but also informs about body-related
      aspects such as posture. Here, we asked whether, accordingly, visual information
      induces body-related, or merely abstract, perceptual-spatial constraints in
      bimanual movement guidance. Human participants made rhythmic, symmetrical and
      parallel, bimanual index finger movements with the hands held in the same or
      different orientations. Performance was more accurate for symmetrical than
      parallel movements in all postures, but additionally when homologous muscles were
      concurrently active, such as when parallel movements were performed with
      differently rather than identically oriented hands. Thus, both perceptual and
      anatomical constraints were evident. We manipulated visual feedback with a mirror
      between the hands, replacing the image of the right with that of the left hand
      and creating the visual impression of bimanual symmetry independent of the right
      hand's true movement. Symmetrical mirror feedback impaired parallel, but improved
      symmetrical bimanual performance compared with regular hand view. Critically,
      these modulations were independent of hand posture and muscle homology. Thus,
      visual feedback appears to contribute exclusively to spatial, but not to body
      related, anatomical movement coding in the guidance of bimanual coordination.

PMID- 29196723
TI  - Bayesian Analysis of MicroScale Thermophoresis Data to Quantify Affinity of
      Protein:Protein Interactions with Human Survivin.
AB  - A biomolecular ensemble exhibits different responses to a temperature gradient
      depending on its diffusion properties. MicroScale Thermophoresis technique
      exploits this effect and is becoming a popular technique for analyzing
      interactions of biomolecules in solution. When comparing affinities of related
      compounds, the reliability of the determined thermodynamic parameters often comes
      into question. The thermophoresis binding curves can be assessed by Bayesian
      inference, which provides a probability distribution for the dissociation
      constant of the interacting partners. By applying Bayesian machine learning
      principles, binding curves can be autonomously analyzed without manual
      intervention and without introducing subjective bias by outlier rejection. We
      demonstrate the Bayesian inference protocol on the known survivin:borealin
      interaction and on the putative protein-protein interactions between human
      survivin and two members of the human Shugoshin-like family (hSgol1 and hSgol2).
      These interactions were identified in a protein microarray binding assay against
      survivin and confirmed by MicroScale Thermophoresis.

PMID- 29196724
TI  - Hierarchically porous, and Cu- and Zn-containing gamma-AlOOH mesostrands as
      adjuvants for cancer immunotherapy.
AB  - Alum is the only licensed adjuvant by Food and Drug Administration of USA used in
      many human vaccines and has excellent safety record in clinical applications.
      However, alum hardly induces T helper 1 (Th1) immune responses that are required
      for anti-tumor immunity. In the present study, we fabricated hierarchical copper-
      and zinc- buds dressing gamma-AlOOH mesostrands (Cu- and Zn-AMSs) with randomly
      wrinkled morphology, mesoscale void- or cave-like pockets, high-exposed surface
      coverage sites, and positive charge streams in saline. We confirmed that Cu- and
      Zn-AMSs promoted intracellular uptake of model cancer antigen (ovalbumin, OVA) by
      THP-1-differentiated macrophage-like cells in vitro. Moreover, Cu- and Zn-AMSs
      enhanced maturation and cytokine release of bone marrow dendritic cells in vitro.
      In vivo study demonstrated that Cu- and Zn-AMSs markedly induced anti-tumor
      immunity and enhanced CD4+ and CD8+ T cell populations in splenocytes of mice.
      These findings demonstrated that hierarchical copper- and zinc- buds dressing
      gamma-AlOOH mesostrands, which are oriented in randomly wrinkled matrice, are
      suitable platforms as novel adjuvants for cancer immunotherapy.

PMID- 29196725
TI  - Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine
      receptor subunits in smoking-cessation therapies.
AB  - Smoking-cessation therapy reduces the risk of smoking-related diseases, but is
      successful only in a fraction of smokers. There is growing evidence that genetic
      variations in nicotinic acetylcholine receptor (nAChR) subunits influence the
      risk of nicotine dependence and the ability to quit smoking. To investigate the
      role of polymorphisms in nAChR genes on smoking quantity and the outcome of
      smoking-cessation therapies, we carried out an association study on 337 smokers
      who underwent pharmacotherapy with varenicline, bupropion, nicotine replacement
      therapy (NRT) alone, or NRT plus bupropion. Smoking habit and abstention were
      assessed from the number of cigarettes smoked per day (CPD) and the exhaled CO
      (eCO), at baseline and up to 12 months. We genotyped seven polymorphisms in genes
      encoding the nAChR subunits CHRNA4, CHRNA5, and CHRNB2. At baseline, both CPD and
      eCO were associated with polymorphisms in the CHRNA5 locus (rs503464, rs55853698,
      rs55781567 and rs16969968; P < 0.01). rs503464, a variant in the 5'-UTR of
      CHRNA5, was also associated with short-, mid- and long-term responses to therapy
      (P = 0.011, P = 0.0043, P = 0.020, respectively), although after correction for
      multiple testing only the association at the mid-term assessment remained
      significant (FDR = 0.03). These data support the role of individual genetic
      makeup in the ability to quit smoking.

PMID- 29196726
TI  - Emergence of BA9 genotype of human respiratory syncytial virus subgroup B in
      China from 2006 to 2014.
AB  - A study was conducted to investigate the circulation of HRSV subgroup B (HRSVB)
      in China in recent years. HRSVB sequences from 365 samples collected in 1991,
      2004 and 2008-2014 in China, together with 332 Chinese HRSVB sequences obtained
      from GenBank were analyzed to determine the geographic and yearly distribution of
      HRSVB. Phylogenetic analysis revealed these HRSVB sequences clustered into 4
      genotypes with different frequencies: BA (83%), CB1 (11%), SAB (3.0%) and GB3
      (0.7%). Between 2005 and 2013, there was a co-circulation of BA and non-BA
      genotypes in China. Genotypes BA9 and BA10 were two of the main BA genotypes
      detected in this study. Genotype BA9 was first detected in China in 2006 and
      became the predominant HRSVB genotype circulating in China from 2008 to 2014.
      Three different lineages were detected for both genotypes BA9 and BA10. Time to
      the most recent common ancestor for genotypes BA9 and BA10 was estimated for
      years 1997 and 1996, respectively. Results of this study not only contribute to
      the understanding of the circulation pattern, but also the phylogenetic pattern
      and evolution of HRSVB in China from 1991 to 2014.

PMID- 29196727
TI  - Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak
      PARP inhibitory activity.
AB  - Rosemary extract is used in food additives and traditional medicine and has been
      observed to contain anti-tumor activity. In this study, rosemary extract is
      hypothesized to induce synthetic lethality in BRCA2 deficient cells by PARP
      inhibition. Chinese hamster lung V79 cells and its mutant cell lines, V-C8 (BRCA2
      deficient) and V-C8 with BRCA2 gene correction were used. Rosemary extract and
      its major constituent chemicals were tested for their cytotoxicity by colony
      formation assay in cells of different BRCA2 status. The latter chemicals were
      tested for inhibitory effect of poly (ADP-ribose) polymerase (PARP) activity in
      vitro and in vivo. Rosemary has shown selective cytotoxicity against V-C8 cells
      (IC50 17 ug/ml) compared to V79 cells (IC50 26 ug/ml). Among tested chemicals,
      gallic acid and carnosic acid showed selective cytotoxicity to V-C8 cells along
      with PARP inhibitory effects. Carnosol showed comparative PARP inhibitory effects
      at 100 uM compared to carnosic acid and gallic acid, but the selective
      cytotoxicity was not observed. In conclusion, we predict that within rosemary
      extract two specific constituent components; gallic acid and carnosic acid were
      the cause for the synthetic lethality.

PMID- 29196728
TI  - Diverse and complex male polymorphisms in Odontolabis stag beetles (Coleoptera:
      Lucanidae).
AB  - When male animals engage in intrasexual contests then any alternative tactics
      they use can be associated with dimorphisms in the expression of weapons. Some
      species have recently been found to exhibit trimorphism in their weaponry,
      suggesting that the processes leading to their evolution and maintenance of these
      polymorphisms can be more complex than previously thought. Here, we describe the
      extraordinary diversity of polymorphism within the genus Odontolabis: there are
      dimorphic species (O. siva and O. platynota), trimorphic species (O. cuvera, as
      previously described, and O. sommeri s.stricto) and, uniquely, tetramorphic
      species, with males of O. sommeri lowei and O. brookeana showing four clearly
      differentiated male morphs: small "Gammas", "Alphas" which express large, long
      mandibles, "Betas" which have long mandibles with different morphology and
      "Boltcutters", with short, wide mandibles. Such polymorphisms are usually thought
      of as being maintained as a status-dependent conditional strategy, but we found
      only one size threshold: in most cases males develop into Gamma males below a
      certain size but there is no relationship between morph and body size amongst the
      larger, 'weaponised' morphs. We suggest that the complex polymorphisms in these
      animals are probably maintained by a combination of a conditional strategy and a
      genetic polymorphism.

PMID- 29196730
TI  - Spatiotemporal modeling and prediction of soil heavy metals based on
      spatiotemporal cokriging.
AB  - Soil heavy metals exhibit significant spatiotemporal variability and are strongly
      correlated with other soil heavy metals. Thus, other heavy metals can be used to
      improve the accuracy of predictions when performing spatiotemporal predictions of
      soil heavy metals within a given area. In this study, we propose the
      spatiotemporal cokriging (STCK) method to enable the use of historical sampling
      points and co-variables in the spatial prediction of soil heavy metals. Moreover,
      experimental spatiotemporal (ST) semivariogram and ST cross-semivariogram
      computational methods, a fitting strategy to the ST semivariogram and ST cross
      semivariogram models based on the Bilonick model, and the STCK interpolation
      algorithm are introduced; these methods are based on spatiotemporal kriging (STK)
      and cokriging (CK). The data used in this study consist of measurements of soil
      heavy metals from 2010 to 2014 in Wuhan City, China. The results show that the
      behavior of predictions of the concentrations of heavy metals in soils is
      physically more realistic, and the prediction uncertainties are slightly smaller,
      when STCK is used with greater numbers of co-variables and neighboring points.

PMID- 29196729
TI  - Peripheral T follicular helper Cells Make a Difference in HIV Reservoir Size
      between Elite Controllers and Patients on Successful cART.
AB  - HIV latency is the main barrier to HIV eradication. Peripheral T follicular
      helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed
      the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV
      replication control. Twenty HIV-infected patients with suppressed HIV replication
      were included, with 10 elite controllers (EC) and 10 treated (TX) individuals.
      The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh,
      and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay. Inter-group
      and intra-group differences were tested using non-parametric tests. Compared with
      the TX patients, the EC patients had smaller HIV reservoir not only in Trm but
      also in pTfh and non-pTfh subsets of memory CD4+ T-cells. The largest differences
      were observed in pTfh cells (p = 0.025). The pTfh and non-pTfh cells harbored
      similar levels of HIV-DNA in the EC (p = 0.60) and TX patients (p = 0.17);
      however, the contribution to HIV-DNA levels in memory CD4+ T-cells varied among
      the pTfh and non-pTfh subsets in both groups of patients. The EC patients showed
      smaller HIV reservoir in memory CD4+ cells, especially in the pTfh subset, a
      population of cells with a pivotal role in the antiviral immune response,
      suggesting a potential link between low levels of infection in pTfh cells and the
      ability of the EC patients to spontaneously control HIV replication.

PMID- 29196731
TI  - Influenza virus Matrix Protein M1 preserves its conformation with pH, changing
      multimerization state at the priming stage due to electrostatics.
AB  - Influenza A virus matrix protein M1 plays an essential role in the virus
      lifecycle, but its functional and structural properties are not entirely defined.
      Here we employed small-angle X-ray scattering, atomic force microscopy and zeta
      potential measurements to characterize the overall structure and association
      behavior of the full-length M1 at different pH conditions. We demonstrate that
      the protein consists of a globular N-terminal domain and a flexible C-terminal
      extension. The globular N-terminal domain of M1 monomers appears preserved in the
      range of pH from 4.0 to 6.8, while the C-terminal domain remains flexible and the
      tendency to form multimers changes dramatically. We found that the protein
      multimerization process is reversible, whereby the binding between M1 molecules
      starts to break around pH 6. A predicted electrostatic model of M1 self-assembly
      at different pH revealed a good agreement with zeta-potential measurements,
      allowing one to assess the role of M1 domains in M1-M1 and M1-lipid interactions.
      Together with the protein sequence analysis, these results provide insights into
      the mechanism of M1 scaffold formation and the major role of the flexible and
      disordered C-terminal domain in this process.

PMID- 29196732
TI  - Human CRMP4 mutation and disrupted Crmp4 expression in mice are associated with
      ASD characteristics and sexual dimorphism.
AB  - Autism spectrum disorders (ASD) are more common among boys than girls. The
      mechanisms responsible for ASD symptoms and their sex differences remain mostly
      unclear. We previously identified collapsin response mediator protein 4 (CRMP4)
      as a protein exhibiting sex-different expression during sexual differentiation of
      the hypothalamic sexually dimorphic nucleus. This study investigated the
      relationship between the sex-different development of autistic features and CRMP4
      deficiency. Whole-exome sequencing detected a de novo variant (S541Y) of CRMP4 in
      a male ASD patient. The expression of mutated mouse CRMP4 S540Y, which is
      homologous to human CRMP4 S541Y, in cultured hippocampal neurons derived from
      Crmp4-knockout (KO) mice had increased dendritic branching, compared to those
      transfected with wild-type (WT) Crmp4, indicating that this mutation results in
      altered CRMP4 function in neurons. Crmp4-KO mice showed decreased social
      interaction and several alterations of sensory responses. Most of these changes
      were more severe in male Crmp4-KO mice than in females. The mRNA expression
      levels of some genes related to neurotransmission and cell adhesion were altered
      in the brain of Crmp4-KO mice, mostly in a gender-dependent manner. These results
      indicate a functional link between a case-specific, rare variant of one gene,
      Crmp4, and several characteristics of ASD, including sexual differences.

PMID- 29196733
TI  - Regulation of HMGB3 by antitumor miR-205-5p inhibits cancer cell aggressiveness
      and is involved in prostate cancer pathogenesis.
AB  - Our recent determination of a microRNA (miRNA) expression signature in prostate
      cancer (PCa) revealed that miR-205-5p was significantly reduced in PCa tissues
      and that it acted as an antitumor miRNA. The aim of this study was to identify
      oncogenic genes and pathways in PCa cells that were regulated by antitumor miR
      205-5p. Genome-wide gene expression analyses and in silico miRNA database
      searches showed that 37 genes were putative targets of miR-205-5p regulation.
      Among those genes, elevated expression levels of seven in particular (HMGB3,
      SPARC, MKI67, CENPF, CDK1, RHOU, and POLR2D) were associated with a shorter
      disease-free survival in a large number of patients in the The Cancer Genome
      Atlas (TCGA) database. We focused on high-mobility group box 3 (HMGB3) because it
      was the most downregulated by ectopic expression of miR-205-5p in PC3 cells and
      its expression was involved in PCa pathogenesis. Luciferase reporter assays
      showed that HMGB3 was directly regulated by miR-205-5p in PCa cells. Knockdown
      studies using si-HMGB3 showed that expression of HMGB3 enhanced PCa cell
      aggressiveness. Overexpression of HMGB3/HMGB3 was confirmed in naive PCa and
      castration-resistant PCa (CRPC) clinical specimens. Novel approaches to analysis
      of antitumor miRNA-regulated RNA networks in PCa cells may provide new insights
      into the pathogenic mechanisms of the disease.

PMID- 29196734
TI  - Possible Tomonaga-Luttinger spin liquid state in the spin-1/2 inequilateral
      diamond-chain compound K3Cu3AlO2(SO4)4.
AB  - K3Cu3AlO2(SO4)4 is a highly one-dimensional spin-1/2 inequilateral diamond-chain
      antiferromagnet. Spinon continuum and spin-singlet dimer excitations are observed
      in the inelastic neutron scattering spectra, which is in excellent agreement with
      a theoretical prediction: a dimer-monomer composite structure, where the dimer is
      caused by strong antiferromagnetic (AFM) coupling and the monomer forms an almost
      isolated quantum AFM chain controlling low-energy excitations. Moreover, muon
      spin rotation/relaxation spectroscopy shows no long-range ordering down to 90 mK,
      which is roughly three orders of magnitude lower than the exchange interaction of
      the quantum AFM chain. K3Cu3AlO2(SO4)4 is, thus, regarded as a compound that
      exhibits a Tomonaga-Luttinger spin liquid behavior at low temperatures close to
      the ground state.

PMID- 29196735
TI  - Considerations for spectroscopy of liquid-exfoliated 2D materials: emerging
      photoluminescence of N-methyl-2-pyrrolidone.
AB  - N-methyl-2-pyrrolidone (NMP) has been shown to be the most effective solvent for
      liquid phase exfoliation and dispersion of a range of 2D materials including
      graphene, molybdenum disulphide (MoS2) and black phosphorus. However, NMP is also
      known to be susceptible to sonochemical degradation during exfoliation. We report
      that this degradation gives rise to strong visible photoluminescence of NMP.
      Sonochemical modification is shown to influence exfoliation of layered materials
      in NMP and the optical absorbance of the solvent in the dispersion. The emerging
      optical properties of the degraded solvent present challenges for spectroscopy of
      nanomaterial dispersions; most notably the possibility of observing solvent
      photoluminescence in the spectra of 2D materials such as MoS2, highlighting the
      need for stable solvents and exfoliation processes to minimise the influence of
      solvent degradation on the properties of liquid-exfoliated 2D materials.

PMID- 29196736
TI  - Continuous positive airway pressure delivery during less invasive surfactant
      administration: a physiologic study.
AB  - OBJECTIVE: We sought to investigate the pressure delivery during less invasive
      surfactant administration, as we hypothesize that it might be reduced. STUDY
      DESIGN: Physiologic in vitro study in a ventilation lab, using different pressure
      generators, levels, and leaks in a model of neonatal airways/lung mimicking
      mechanical characteristics of respiratory distress syndrome. Pressure was
      measured at the lung and verified in vivo measuring pharyngeal pressure in 19
      neonates under same conditions. Data were analyzed using repeated measures
      analysis of variance. RESULTS: Pressure delivery in vitro is significantly and
      variably reduced during minimally invasive surfactant administration: pressure
      loss is ~99% and ~10-97%, during mouth opening and closure, respectively.
      Pressure loss seems independent from the type of CPAP and interface. In vivo
      measurements showed similar pressure drops. CONCLUSIONS: Pressure transmission
      during minimally invasive surfactant administration is significantly reduced or
      totally absent. Pressure drop occurs despite the increased airway resistances and
      the airflow limitation due to the tracheal catheterization, but is independent
      from the type of pressure generator and interface.

PMID- 29196737
TI  - Spontaneous Phase Transfer-Mediated Selective Removal of Heavy Metal Ions Using
      Biocompatible Oleic Acid.
AB  - Here, we propose an environmentally benign removal technique for heavy metal ions
      based on selective and spontaneous transfer to oleic acid. The ions can be
      removed via (1) the selective and rapid complexation with the carboxylic end of
      oleic acid at an oleic acid/water interface, and (2) the diffusion of such
      complex into the oleic acid layer. A wide variety of heavy metal ions such as
      Cu2+, Pb2+, Zn2+, and Ni2+ can be selectively removed over K+ and Na+. For
      example, the concentration of Cu2+ is reduced to below 1.3 ppm within 24 h, which
      corresponds to the level of Cu2+ permitted by the Environmental Protection
      Agency. The addition of ethylenediamine ligand to the metal ion solutions is also
      shown to enhance the phase transfer. The removal efficiency is increased by up to
      6 times when compared with that in the absence of the ligand and follows the
      order, Cu2+ (99%) > Pb2+ (96%) > Zn2+ (95%) > Ni2+ (65%). Moreover, the removal
      time can be shortened from 24 h to 1 h. The effect of an emulsion induced by a
      mechanical agitation on the removal of heavy metal ion is also studied.

PMID- 29196738
TI  - Validation of SinoSCORE for isolated CABG operation in East China.
AB  - From January 2010 to December 2016, 1616 consecutive patients who underwent
      isolated coronary artery bypass grafting (CABG) were evaluated for their
      predicted mortality according to the online Sino System for Coronary Operative
      Risk Evaluation (SinoSCORE), European System for Cardiac Operative Risk
      Evaluation II (EuroSCORE II) and Society of Thoracic Surgeons (STS) risk
      evaluation system. The calibration and discrimination in the total and in the
      subsets were assessed by the Hosmer-Lemeshow (H-L) statistics and by the C
      statistics respectively, to evaluate the efficiency of the three risk evaluation
      systems. The realized mortality was 1.92% (31/1616). The predictive mortality of
      SinoSCORE, EuroSCORE II and STS risk evaluation system were 1.35%, 1.74% and
      1.05%, respectively. SinoSCORE achieved best discrimination. When grouping by
      risk, SinoSCORE also achieved the best discrimination in high-risk group,
      followed by STS risk evaluation system and EuroSCORE II while SinoSCORE and
      EuroSCORE II had excellent performance in low-risk group. In terms of
      calibration, SinoSCORE, EuroSCORE II and STS risk evaluation system all achieved
      positive calibrations (H-L: P > 0.05) in the overall population and grouped
      subsets. SinoSCORE achieved good predictive efficiency in East China patients
      undergoing isolated CABG and showed no compromise when compared with EuroSCORE II
      and STS risk evaluation system.

PMID- 29196739
TI  - Imaging viscosity of intragranular mucin matrix in cystic fibrosis cells.
AB  - Abnormalities of mucus viscosity play a critical role in the pathogenesis of
      several respiratory diseases, including cystic fibrosis. Currently, there are no
      approaches to assess the rheological properties of mucin granule matrices in live
      cells. This is the first example of the use of a molecular rotor, a BODIPY dye,
      to quantitatively visualize the viscosity of intragranular mucin matrices in a
      large population of individual granules in differentiated primary bronchial
      epithelial cells using fluorescence lifetime imaging microscopy.

PMID- 29196740
TI  - Rapid and Sensitive SERS Detection of Bisphenol A Using Self-assembled Graphitic
      Substrates.
AB  - We have prepared and tested a new surface enhanced Raman scattering (SERS)
      substrate based on self-assembled graphitic sheets to detect bisphenol A (BPA) in
      plastic consumer goods. Transmission electron microscopy (TEM) and atomic-force
      microscopy (AFM) were used to characterize the structure of the graphitic sheets
      and showed a lattice spacing of 0.24 nm and layer height of 0.34 nm. These values
      were comparable to single monolayer graphene. The effective SERS detection limit
      of this method is 1 MUM BPA, which is lower than the European Union specific
      migration limit for BPA of 0.6 mg/kg (2.6 MUM). When used in salt solutions,
      graphitic sheets exhibited ultra-sensitivity toward BPA of 0.025 M to 2 M, which
      was broader than physiological ionic strength (0.14 M) and urinary NaCl (0.17 M).
      Our results demonstrated that this graphitic sheet based SERS detection platform
      can be used to determine BPA levels leached from commercial polycarbonate plastic
      products and for on-site rapid analysis with good results.

PMID- 29196741
TI  - Bayesian inference of epidemiological parameters from transmission experiments.
AB  - Epidemiological parameters for livestock diseases are often inferred from
      transmission experiments. However, there are several limitations inherent to the
      design of such experiments that limits the precision of parameter estimates. In
      particular, infection times and latent periods cannot be directly observed and
      infectious periods may also be censored. We present a Bayesian framework
      accounting for these features directly and employ Markov chain Monte Carlo
      techniques to provide robust inferences and quantify the uncertainty in our
      estimates. We describe the transmission dynamics using a susceptible-exposed
      infectious-removed compartmental model, with gamma-distributed transition times.
      We then fit the model to published data from transmission experiments for foot
      and-mouth disease virus (FMDV) and African swine fever virus (ASFV). Where the
      previous analyses of these data made various assumptions on the unobserved
      processes in order to draw inferences, our Bayesian approach includes the
      unobserved infection times and latent periods and quantifies them along with all
      other model parameters. Drawing inferences about infection times helps identify
      who infected whom and can also provide insights into transmission mechanisms.
      Furthermore, we are able to use our models to measure the difference between the
      latent periods of inoculated and contact-challenged animals and to quantify the
      effect vaccination has on transmission.

PMID- 29196742
TI  - Whitening and Impaired Glucose Utilization of Brown Adipose Tissue in a Rat Model
      of Type 2 Diabetes Mellitus.
AB  - Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes
      and obesity due to its ability to increase glucose expenditure. In a genetic rat
      model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose
      utilization of BAT by 18F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and
      Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to
      imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild
      calorie restriction (ZDF-CR) group. Dynamic 18F-FDG PET using a dedicated small
      animal PET system was performed under hyperinsulinemic-euglycemic clamp. 18F-FDG
      PET identified intense inter-scapular BAT glucose uptake in all ZL control rats,
      while no focally increased 18F-FDG uptake was detected in all ZDF-ND rats. Mild
      but significant improved BAT tracer uptake was identified after calorie
      restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits
      were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL
      controls, while UCP-1 and mitochondrial concentrations were significantly
      decreased. Whitening and severely impaired insulin-stimulated glucose uptake in
      BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie
      restriction partially restored the impaired BAT glucose uptake.

PMID- 29196743
TI  - Repair of the TGFBI gene in human corneal keratocytes derived from a granular
      corneal dystrophy patient via CRISPR/Cas9-induced homology-directed repair.
AB  - Granular corneal dystrophy (GCD) is an autosomal dominant hereditary disease in
      which multiple discrete and irregularly shaped granular opacities are deposited
      in the corneal stroma. GCD is caused by a point mutation in the transforming
      growth factor-beta-induced (TGFBI) gene, located on chromosome 5q31. Here, we
      report the first successful application of CRISPR-Cas9-mediated genome editing
      for the correction of a TGFBI mutation in GCD patient-derived primary corneal
      keratocytes via homology-directed repair (HDR). To correct genetic defects in GCD
      patient cells, we designed a disease-specific guide RNA (gRNA) targeting the
      R124H mutation of TGFBI, which causes GCD type 2 (GCD2). An R124H mutation in
      primary human corneal keratocytes derived from a GCD2 patient was corrected by
      delivering a CRISPR plasmid expressing Cas9/gRNA and a single-stranded
      oligodeoxynucleotide HDR donor template in vitro. The gene correction efficiency
      was 20.6% in heterozygous cells and 41.3% in homozygous cells. No off-target
      effects were detected. These results reveal a new therapeutic strategy for GCD2;
      this method may also be applicable to other heredity corneal diseases.

PMID- 29196744
TI  - A simple high throughput assay to evaluate water consumption in the fruit fly.
AB  - Water intake is essential for survival and thus under strong regulation. Here, we
      describe a simple high throughput system to monitor water intake over time in
      Drosophila. The design of the assay involves dehydrating fly food and then adding
      water back separately so flies either eat or drink. Water consumption is then
      evaluated by weighing the water vessel and comparing this back to an evaporation
      control. Our system is high throughput, does not require animals to be
      artificially dehydrated, and is simple both in design and implementation. Initial
      characterisation of homeostatic water consumption shows high reproducibility
      between biological replicates in a variety of experimental conditions. Water
      consumption was dependent on ambient temperature and humidity and was equal
      between sexes when corrected for mass. By combining this system with the
      Drosophila genetics tools, we could confirm a role for ppk28 and DopR1 in
      promoting water consumption, and through functional investigation of RNAseq data
      from dehydrated animals, we found DopR1 expression in the mushroom body was
      sufficient to drive consumption and enhance water taste sensitivity. Together, we
      provide a simple high throughput water consumption assay that can be used to
      dissect the cellular and molecular machinery regulating water homeostasis in
      Drosophila.

PMID- 29196745
TI  - Characterization of liposomal carriers for the trans-scleral transport of
      Ranibizumab.
AB  - Age-related macular degeneration (AMD) is a leading cause of blindness in the
      modern world. The standard treatment regimen for neovascular AMD is the
      monthly/bimonthly intravitreal injection of anti-VEGF agents such as ranibizumab
      or aflibercept. However, these repeated invasive injections can lead to sight
      threatening complications. Sustained delivery by encapsulation of the drug in
      carriers is a way to reduce the frequency of these injections. Liposomes are
      biocompatible, non-toxic vesicular nanocarriers, which can be used to encapsulate
      therapeutic agents to provide sustained release. The protein encapsulation was
      performed by a modified dehydration-rehydration (DRV) method. The liposomes
      formed were characterized for size, zeta potential, encapsulation efficiency,
      stability, in vitro release, and ex vivo release profiles. In addition, the
      localization of the liposomes themselves was studied ex vivo. Entrapment
      efficiency of ranibizumab into 100-nm liposomes varied from 14.7 to 57.0%.
      Negatively-charged liposomes prepared from DPPC-DPPG were found to have the
      slowest release with a low initial burst release compared to the rest of
      liposomal formulations. The ex vivo protein release was found to slower than the
      in vitro protein release for all samples. In conclusion, the DPPC-DPPG liposomes
      significantly improved the encapsulation and release profile of ranibizumab.

PMID- 29196747
TI  - A small cassette enables conditional gene inactivation by CRISPR/Cas9.
AB  - The availability of CRISPR/Cas9 technology has enabled the rapid establishment of
      gene knockouts in many cell types and even whole organisms. However, conditional
      inactivation of essential genes remains a challenge. We devised an approach named
      DECAI (DEgradation based on Cre-regulated- Artificial Intron). It utilizes a
      small cassette of just 201 nucleotides that is inserted into the coding exon of a
      target gene using CRISPR/Cas9 technology and homology-directed repair. As its
      sequence is derived from an artificial intron, the cassette is removed by the
      splicing machinery and thus leaves no trace in the "off-state". Upon activation
      with Cre recombinase ("on-state"), the intron is crippled and the target gene is
      disrupted by a series of stop codons. We exemplify the utility of this approach
      on several non-essential and essential human genes. Clones bearing the
      conditional knockout cassette are recovered at frequencies above 5% and cassette
      function can be traced at the genomic DNA and the mRNA level. Importantly,
      cassette activation leads to loss of gene expression as judged by flow cytometry,
      Western blot or immunofluorescence. Altogether, this highlights the broad utility
      of the approach for conditional gene inactivation and suggests that this tool
      could be used to study the loss-of-function phenotypes of essential genes.

PMID- 29196746
TI  - Diabetes Aggravates Post-ischaemic Renal Fibrosis through Persistent Activation
      of TGF-beta1 and Shh Signalling.
AB  - Diabetes is a risk factor for acute kidney injury (AKI) and chronic kidney
      disease (CKD). Diabetic patients are easy to progress to CKD after AKI.
      Currently, activation of fibrotic signalling including transforming growth factor
      beta1 (TGF-beta1) is recognized as a key mechanism in CKD. Here, we investigated
      the influence of diabetes on CKD progression after AKI by using a unilateral
      renal ischaemia-reperfusion injury (IRI) model in diabetic mice. IRI induced
      extensive tubular injury, fibrosis and lymphocyte recruitment at 3 weeks after
      IRI, irrespective of diabetes. However, diabetes showed sustained tubular injury
      and markedly increased fibrosis and lymphocyte recruitment compared with non
      diabetes at 5 week after IRI. The mRNAs and proteins related to TGF-beta1 and
      sonic hedgehog (Shh) signalling were significantly higher in diabetic versus non
      diabetic IRI kidneys. During the in vitro study, the hyperglycaemia induced the
      activation of TGF-beta1 and Shh signalling and also increased profibrogenic
      phenotype change. However, hyperglycaemic control with insulin did not improve
      the progression of renal fibrosis and the activation of TGF-beta1 and Shh
      signalling. In conclusion, diabetes promotes CKD progression of AKI via
      activation of the TGF-beta1 and Shh signalling pathways, but insulin treatment
      was not enough for preventing the progression of renal fibrosis.

PMID- 29196748
TI  - Cell-Free DNA Kinetics in a Pre-Clinical Model of Head and Neck Cancer.
AB  - In cancer patients, circulating tumour-derived DNA (ctDNA) levels imperfectly
      reflect disease burden apparent on medical imaging. Further evaluation of ctDNA
      levels over time is needed to better understand the correlation with tumour
      growth and therapeutic response. We describe ctDNA kinetics within an orthotopic,
      immunocompetent preclinical rabbit model of local-regionally advanced head and
      neck squamous cell carcinoma (HNSCC). Monitoring primary tumour and metastatic
      lymph node volume by computed tomography (CT), we observed a correlation between
      ctDNA levels and tumour burden. We found that ctDNA detection could precede
      evidence of tumour on CT. Sensitivity and specificity of ctDNA detection in this
      model was 90.2% (95% C.I.: 76.9-97.3%) and 85.7% (95% C.I.: 67.3-96.0%),
      respectively. Rapid tumour growth followed by auto-necrosis and tumour volume
      contraction produced a spike in ctDNA levels, suggesting that viable tumour cells
      may be required for sustained ctDNA release. Following surgical resection, both
      ctDNA and total plasma DNA were correlated with recurrent tumour volume. Our
      results reveal the complex kinetic behaviour of ctDNA and total plasma DNA upon
      tumour growth or surgery. This pre-clinical model could be useful for future
      studies focused on elucidating mechanisms of ctDNA release into the circulation
      from primary and metastatic sites.

PMID- 29196749
TI  - Physics of Efficiency Droop in GaN:Eu Light-Emitting Diodes.
AB  - The internal quantum efficiency (IQE) of an electrically-driven GaN:Eu based
      device for red light emission is analyzed in the framework of a current injection
      efficiency model (CIE). The excitation path of the Eu+3 ion is decomposed in a
      multiple level system, which includes the carrier transport phenomena across the
      GaN/GaN:Eu/GaN active region of the device, and the interactions among traps,
      Eu+3 ions and the GaN host. The identification and analysis of the limiting
      factors of the IQE are accomplished through the CIE model. The CIE model provides
      a guidance for high IQE in the electrically-driven GaN:Eu based red light
      emitters.

PMID- 29196751
TI  - The solvability of quantum k-pair network in a measurement-based way.
AB  - Network coding is an effective means to enhance the communication efficiency. The
      characterization of network solvability is one of the most important topic in
      this field. However, for general network, the solvability conditions are still a
      challenge. In this paper, we consider the solvability of general quantum k-pair
      network in measurement-based framework. For the first time, a detailed account of
      measurement-based quantum network coding(MB-QNC) is specified systematically.
      Differing from existing coding schemes, single qubit measurements on a pre-shared
      graph state are the only allowed coding operations. Since no control operations
      are concluded, it makes MB-QNC schemes more feasible. Further, the sufficient
      conditions formulating by eigenvalue equations and stabilizer matrix are
      presented, which build an unambiguous relation among the solvability and the
      general network. And this result can also analyze the feasibility of sharing k
      EPR pairs task in large-scale networks. Finally, in the presence of noise, we
      analyze the advantage of MB-QNC in contrast to gate-based way. By an instance
      network [Formula: see text], we show that MB-QNC allows higher error thresholds.
      Specially, for X error, the error threshold is about 30% higher than 10% in gate
      based way. In addition, the specific expressions of fidelity subject to some
      constraint conditions are given.

PMID- 29196750
TI  - A Novel Y-Specific Long Non-Coding RNA Associated with Cellular Lipid
      Accumulation in HepG2 cells and Atherosclerosis-related Genes.
AB  - There is an increasing appreciation for the role of the human Y chromosome in
      phenotypic differences between the sexes in health and disease. Previous studies
      have shown that genetic variation within the Y chromosome is associated with
      cholesterol levels, which is an established risk factor for atherosclerosis, the
      underlying cause of coronary artery disease (CAD), a major cause of morbidity and
      mortality worldwide. However, the exact mechanism and potential genes implicated
      are still unidentified. To date, Y chromosome-linked long non-coding RNAs
      (lncRNAs) are poorly characterized and the potential link between these new
      regulatory RNA molecules and hepatic function in men has not been investigated.
      Advanced technologies of lncRNA subcellular localization and silencing were used
      to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and
      investigate its role in fatty liver-associated atherosclerosis. We found that lnc
      KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to
      changes in genes leading to increased lipid droplets formation in hepatocytes
      resulting in a downstream effect contributing to the chronic inflammatory process
      that underpin CAD. Our findings provide the first evidence for the implication of
      lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation
      associated with atherosclerosis and CAD in men.

PMID- 29196752
TI  - Combined genetic approaches yield a 48% diagnostic rate in a large cohort of
      French hearing-impaired patients.
AB  - Hearing loss is the most common sensory disorder and because of its high genetic
      heterogeneity, implementation of Massively Parallel Sequencing (MPS) in
      diagnostic laboratories is greatly improving the possibilities of offering
      optimal care to patients. We present the results of a two-year period of
      molecular diagnosis that included 207 French families referred for non-syndromic
      hearing loss. Our multi-step strategy involved (i) DFNB1 locus analysis, (ii) MPS
      of 74 genes, and (iii) additional approaches including Copy Number Variations, in
      silico analyses, minigene studies coupled when appropriate with complete gene
      sequencing, and a specific assay for STRC. This comprehensive screening yielded
      an overall diagnostic rate of 48%, equally distributed between DFNB1 (24%) and
      the other genes (24%). Pathogenic genotypes were identified in 19 different
      genes, with a high prevalence of GJB2, STRC, MYO15A, OTOF, TMC1, MYO7A and USH2A.
      Involvement of an Usher gene was reported in 16% of the genotyped cohort. Four de
      novo variants were identified. This study highlights the need to develop several
      molecular approaches for efficient molecular diagnosis of hearing loss, as this
      is crucial for genetic counselling, audiological rehabilitation and the detection
      of syndromic forms.

PMID- 29196753
TI  - Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches
      through Micromilling.
AB  - The ability for cells to sense and respond to microenvironmental signals is
      influenced by their three dimensional (3D) surroundings, which includes the
      extracellular matrix (ECM). In the 3D environment, vascular structures supply
      cells with nutrients and oxygen thus affecting cell responses such as motility.
      Interpretation of cell motility studies though is often restricted by the applied
      approaches such as 2D conventional soft lithography methods that have rectangular
      channel cross-sectional morphology. To better simulate cell responses to vascular
      supply in 3D, we developed a cell on a chip system with microfluidic channels
      with curved cross-sections embedded within a 3D collagen matrix that emulates
      anatomical vasculature more closely than inorganic polymers, thus to mimic a more
      physiologically relevant 3D cellular environment. To accomplish this, we
      constructed perfusable microfluidic channels by embedding sacrificial circular
      gelatin vascular templates in collagen, which were removed through temperature
      control. Motile breast cancer cells were pre-seeded into the collagen matrix and
      when presented with a controlled chemical stimulation from the artificial
      vasculature, they migrated towards the vasculature structure. We believe this
      innovative vascular 3D ECM system can be used to provide novel insights into
      cellular dynamics during multidirectional chemokineses and chemotaxis that exist
      in cancer and other diseases.

PMID- 29196754
TI  - Interface and material engineering for zigzag slab lasers.
AB  - Laser damage of zigzag slab lasers occurs at interface between laser crystal and
      SiO2 film. Although an additional HfO2 layer could be used to manipulate electric
      field on the crystal-film interface, their high absorption and polycrystalline
      structure were unacceptable. SiO2 was then doped in HfO2 to suppress its
      crystallization and to achieve low absorption by annealing. HfxSi1-xO2
      nanocomposite layers were then inserted between laser crystal and SiO2 film to
      minimize electric-field at crystal-film interface. Laser damage resistance of
      this new architecture is two times higher than that of traditional zigzag slab
      lasers.

PMID- 29196755
TI  - Novel halos in light kaonic nuclei as an indicator of nuclear equation of state
      at supra-normal densities.
AB  - The sensitive correlations between the low-density halo structure and the high
      density properties of the nuclear equation of state (EOS) are constructed in
      light kaonic nuclei with the relativistic mean-field theory. More specifically,
      the 1p 1/2 halo spreads out linearly with increasing the pressure and sound
      velocity square at supra-normal densities and decreasing the incompressibility at
      saturation density. These results suggest that the novel halo in light kaonic
      nuclei can serve as a sensitive indicator of the nuclear EOS of symmetric matter
      at supra-normal densities. The experimental production and detection of the light
      kaonic nuclei, yet to be available, is discussed in some details at last.

PMID- 29196756
TI  - Magnetic stratigraphic dating of marine hydrogenetic ferromanganese crusts.
AB  - Deep-sea hydrogenetic ferromanganese crusts are both potential polymetallic
      resources and records of long-term environmental changes. For palaeoceanographic
      studies, it is important to construct a detailed and reliable chronological
      framework. Here, we report the results of a detailed magnetostratigraphic and
      rock magnetic study of four hydrogenetic Fe-Mn crusts from the Pacific Ocean (PO
      01), South China Sea (SCS-01, SCS-02) and Indian Ocean (IO-01). Two groups of
      characteristic remanent magnetization directions were defined with nearly
      antipodal normal and reversed polarities for samples PO-01, SCS-01 and SCS-02,
      indicating a primary record of the Earth's magnetic field. The
      magnetostratigraphic framework, established via correlation with the Geomagnetic
      Polarity Time Scale 2012, implies growth rates of 4.82 mm/Ma, 4.95 mm/Ma, 4.48
      mm/Ma and 11.28 mm/Ma for samples PO-01, SCS-01, SCS-02 and IO-01, respectively.
      Rock magnetic measurements revealed that the Fe-Mn crust samples from the Pacific
      Ocean and Indian Ocean were dominated by low coercivity, non-interacting, single
      domain (SD) magnetite particles, whereas the South China Sea samples were
      dominated by SD/pseudo-single-domain (PSD) particles. Multidomain (MD) magnetite
      may also be present in all samples.

PMID- 29196757
TI  - Mitotic slippage and the subsequent cell fates after inhibition of Aurora B
      during tubulin-binding agent-induced mitotic arrest.
AB  - Tubulin-binding agents (TBAs) are designed to target microtubule (MT) dynamics,
      resulting in compromised mitotic spindles and an unsatisfied spindle assembly
      checkpoint. The activity of Aurora B kinase is indispensable for TBA-induced
      mitotic arrest, and its inhibition causes mitotic slippage and postmitotic
      endoreduplication. However, the precise phenomenon underlying mitotic slippage,
      which is caused by treatment with both Aurora B inhibitors and TBAs, and the cell
      fate after postmitotic slippage are not completely understood. Here, we found
      that HeLa and breast cancer cells treated with the different types of TBAs, such
      as paclitaxel and eribulin (MT-stabilizing and MT-destabilizing agents,
      respectively), exhibited distinct behaviors of mitotic slippage on inhibition of
      Aurora B. In such conditions, the cell fates after postmitotic slippage vastly
      differed with respect to cell morphology, cell proliferation, and cytotoxicity in
      short-term culture; that is, the effects of inhibition of Aurora B were
      beneficial for cytotoxicity enhancement in eribulin treatment but not in
      paclitaxel. However, in long-term culture, the cells that survived after mitotic
      slippage underwent endoreduplication and became giant cells in both cases,
      resulting in cellular senescence. We propose that MT-destabilizing agents may be
      more appropriate than MT-stabilizing agents for treating cancer cells with a
      weakened Aurora B kinase activity.

PMID- 29196759
TI  - Functional MRI, ERP, and psychophysical measures show that contextual effects are
      orientation tuned and suppressive.
AB  - The response of V1 neurons to a stimulus placed inside the classical receptive
      field can be modulated by stimuli presented outside the classical receptive
      field. However, the specific nature of these contextual modulations is unknown.
      Both enhancement and suppression have been observed as well as variability across
      measurement methodologies. To assess whether the contextual effect is
      facilitative or suppressive, we measured neural responses to an oriented Gabor
      stimulus ("target") in three conditions: in isolation, with two Gabor flankers
      that were the same orientation as the target, and with two flankers that were
      orthogonal to the target orientation. We show that the target-related fMRI
      response, event-related potential amplitude, and the amount of contrast
      adaptation are all lower when the flankers were the same orientation compared to
      both the isolated and orthogonal conditions. There was no evidence of response
      enhancement. These results all point to an orientation-tuned suppressive effect
      of contextual stimuli measured in the periphery that is well explained by models
      incorporating divisive or subtractive inhibition.

PMID- 29196758
TI  - The role of oxidative stress in the crosstalk between leptin and
      mineralocorticoid receptor in the cardiac fibrosis associated with obesity.
AB  - We have investigated whether mineralocorticoid receptor activation can
      participate in the profibrotic effects of leptin in cardiac myofibroblasts, as
      well as the potential mechanisms involved. The presence of eplerenone reduced the
      leptin-induced increase in protein levels of collagen I, transforming growth
      factor beta, connective tissue growth factor and galectin-3 and the levels of
      both total and mitochondrial of superoxide anion (O2.-) in cardiac
      myofibroblasts. Likewise, the MEK/ERK inhibitor, PD98059, and the PI3/Akt
      inhibitor, LY294002, showed a similar pattern. Mitochondrial reactive oxygen
      species (ROS) scavenger (MitoTempo) attenuated the increase in body weight
      observed in rats fed a high fat diet (HFD). No differences were found in cardiac
      function or blood pressure among any group. However, the cardiac fibrosis and
      enhanced O2.-levels observed in HFD rats were attenuated by MitoTempo, which also
      prevented the increased circulating leptin and aldosterone levels in HFD fed
      animals. This study supports a role of mineralocorticoid receptor in the cardiac
      fibrosis induced by leptin in the context of obesity and highlights the role of
      the mitochondrial ROS in this process.

PMID- 29196760
TI  - Transfer of an induced preferred retinal locus of fixation to everyday life
      visual tasks.
AB  - Subjects develop a preferred retinal locus of fixation (PRL) under simulation of
      central scotoma. If systematic relocations are applied to the stimulus position,
      PRLs manifest at a location in favor of the stimulus relocation. The present
      study investigates whether the induced PRL is transferred to important visual
      tasks in daily life, namely pursuit eye movements, signage reading, and text
      reading. Fifteen subjects with normal sight participated in the study. To develop
      a PRL, all subjects underwent a scotoma simulation in a prior study, where five
      subjects were trained to develop the PRL in the left hemifield, five different
      subjects on the right hemifield, and the remaining five subjects could naturally
      chose the PRL location. The position of this PRL was used as baseline. Under
      central scotoma simulation, subjects performed a pursuit task, a signage reading
      task, and a reading-text task. In addition, retention of the behavior was also
      studied. Results showed that the PRL position was transferred to the pursuit task
      and that the vertical location of the PRL was maintained on the text reading
      task. However, when reading signage, a function-driven change in PRL location was
      observed. In addition, retention of the PRL position was observed over weeks and
      months. These results indicate that PRL positions can be induced and may further
      transferred to everyday life visual tasks, without hindering function-driven
      changes in PRL position.

PMID- 29196761
TI  - Dynamic gaze-position prediction of saccadic eye movements using a Taylor series.
AB  - Gaze-contingent displays have been widely used in vision research and virtual
      reality applications. Due to data transmission, image processing, and display
      preparation, the time delay between the eye tracker and the monitor update may
      lead to a misalignment between the eye position and the image manipulation during
      eye movements. We propose a method to reduce the misalignment using a Taylor
      series to predict the saccadic eye movement. The proposed method was evaluated
      using two large datasets including 219,335 human saccades (collected with an
      EyeLink 1000 system, 95% range from 1 degrees  to 32 degrees ) and 21,844 monkey
      saccades (collected with a scleral search coil, 95% range from 1 degrees  to 9
      degrees ). When assuming a 10-ms time delay, the prediction of saccade movements
      using the proposed method could reduce the misalignment greater than the state-of
      the-art methods. The average error was about 0.93 degrees  for human saccades and
      0.26 degrees  for monkey saccades. Our results suggest that this proposed saccade
      prediction method will create more accurate gaze-contingent displays.

PMID- 29196762
TI  - Neuronal mechanisms underlying differences in spatial resolution between darks
      and lights in human vision.
AB  - Artists and astronomers noticed centuries ago that humans perceive dark features
      in an image differently from light ones; however, the neuronal mechanisms
      underlying these dark/light asymmetries remained unknown. Based on computational
      modeling of neuronal responses, we have previously proposed that such perceptual
      dark/light asymmetries originate from a luminance/response saturation within the
      ON retinal pathway. Consistent with this prediction, here we show that stimulus
      conditions that increase ON luminance/response saturation (e.g., dark
      backgrounds) or its effect on light stimuli (e.g., optical blur) impair the
      perceptual discrimination and salience of light targets more than dark targets in
      human vision. We also show that, in cat visual cortex, the magnitude of the ON
      luminance/response saturation remains relatively constant under a wide range of
      luminance conditions that are common indoors, and only shifts away from the
      lowest luminance contrasts under low mesopic light. Finally, we show that the ON
      luminance/response saturation affects visual salience mostly when the high
      spatial frequencies of the image are reduced by poor illumination or optical
      blur. Because both low luminance and optical blur are risk factors in myopia, our
      results suggest a possible neuronal mechanism linking myopia progression with the
      function of the ON visual pathway.

PMID- 29196763
TI  - Early dynamics of stereoscopic surface slant perception.
AB  - Surface orientation is an important visual primitive that can be estimated from
      monocular or binocular (stereoscopic) signals. Changes in motor planning occur
      within about 200 ms after either type of signal is perturbed, but the time it
      takes for apparent (perceived) slant to develop from stereoscopic cues is not
      known. Apparent slant sometimes develops very slowly (Gillam, Chambers, & Russo,
      1988; van Ee & Erkelens, 1996). However, these long durations could reflect the
      time it takes for the visual system to resolve conflicts between slant cues that
      inevitably specify different slants in laboratory displays (Allison & Howard,
      2000). We used a speed-accuracy tradeoff analysis to measure the time it takes to
      discriminate slant, allowing us to report psychometric functions as a function of
      response time. Observers reported which side of a slanted surface was farther,
      with a temporal deadline for responding that varied block-to-block. Stereoscopic
      slant discrimination rose above chance starting at 200 ms after stimulus onset.
      Unexpectedly, observers discriminated slant from binocular disparity faster than
      texture, and for stereoscopic whole-field stimuli faster than stereoscopic slant
      contrast stimuli. However, performance after the initial deviation from chance
      increased more rapidly for slant-contrast stimuli than whole-field stimuli.
      Discrimination latencies were similar for slants about the horizontal and
      vertical axes, but performance increased faster for slants about the vertical
      axis. Finally, slant from vertical disparity was somewhat slower than slant from
      horizontal disparity, which may reflect cue conflict. These results demonstrate,
      in contradiction with the previous literature, that the perception of slant from
      disparity happens very quickly-in fact, more quickly than the perception of slant
      from texture-and in comparable time to the simple perception of brightness from
      luminance.

PMID- 29196764
TI  - Differences in Trabecular Microarchitecture and Simplified Boundary Conditions
      Limit the Accuracy of Quantitative Computed Tomography-Based Finite Element
      Models of Vertebral Failure.
AB  - Vertebral fractures are common in the elderly, but efforts to reduce their
      incidence have been hampered by incomplete understanding of the failure processes
      that are involved. This study's goal was to elucidate failure processes in the
      lumbar vertebra and to assess the accuracy of quantitative computed tomography
      (QCT)-based finite element (FE) simulations of these processes. Following QCT
      scanning, spine segments (n = 27) consisting of L1 with adjacent intervertebral
      disks and neighboring endplates of T12 and L2 were compressed axially in a
      stepwise manner. A microcomputed tomography scan was performed at each loading
      step. The resulting time-lapse series of images was analyzed using digital volume
      correlation (DVC) to quantify deformations throughout the vertebral body. While
      some diversity among vertebrae was observed on how these deformations progressed,
      common features were large strains that developed progressively in the superior
      third and, concomitantly, in the midtransverse plane, in a manner that was
      associated with spatial variations in microstructural parameters such as
      connectivity density. Results of FE simulations corresponded qualitatively to the
      measured failure patterns when boundary conditions were derived from DVC
      displacements at the endplate. However, quantitative correspondence was often
      poor, particularly when boundary conditions were simplified to uniform
      compressive loading. These findings suggest that variations in trabecular
      microstructure are one cause of the differences in failure patterns among
      vertebrae and that both the lack of incorporation of these variations into QCT
      based FE models and the oversimplification of boundary conditions limit the
      accuracy of these models in simulating vertebral failure.

PMID- 29196766
TI  - Parafoveal Photoreceptor Abnormalities in Asymptomatic Patients With RP1L1
      Mutations in Families With Occult Macular Dystrophy.
AB  - Purpose: To report the clinical characteristics of asymptomatic cases with RP1L1
      gene mutations in four families with occult macular dystrophy (OMD). Methods:
      Four asymptomatic cases from four families were selected from a cohort of 40
      subjects (16 families) with RP1L1 pathogenic variants. Clinical data of the four
      asymptomatic cases and three symptomatic patients in the same families were
      reviewed. The three asymptomatic cases did not have any visual symptoms in either
      eye, and one was unilaterally affected. Ophthalmologic examinations, including
      spectral-domain optical coherence tomography (OCT) were performed, and the
      morphologic characteristics of the photoreceptor layer of the asymptomatic cases
      were compared to those of the symptomatic patients within the same family.
      Results: The OCT images demonstrated photoreceptor abnormalities in the
      parafoveal regions in all of the four asymptomatic cases (i.e., absence of the
      interdigitation zone and blurring of the ellipsoid zone). However, these
      microstructures were preserved at the foveal center. The longitudinal
      reflectivity profiles clearly identified this distinct pattern in the
      asymptomatic cases. In contrast, no distinct abnormalities were detected by other
      examinations including perimetry, fundus autofluorescence images, and multifocal
      electroretinograms (ERGs). Conclusions: The sparing of the central foveal
      photoreceptor layer accounts for the well-preserved visual acuity in the
      asymptomatic patients. The sparing may represent either the initial phase of
      typical OMD or a subtype of macular lesion associated with OMD. It is necessary
      to examine asymptomatic subjects in families with OMD because some of them may
      progress to the typical phenotype of OMD.

PMID- 29196765
TI  - Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded
      Filament Proteins.
AB  - Purpose: The objective of this study was to understand the molecular and
      physiologic mechanisms behind the lens cataract differences in Aquaporin 0
      knockout-Heterozygous (AQP0-Htz) mice developed in C57 and FVB (lacks beaded
      filaments [BFs]) strains. Methods: Lens transparency was studied using dark field
      light microscopy. Water permeability (Pf) was measured in fiber cell membrane
      vesicles. Western blotting/immunostaining was performed to verify expression of
      BF proteins and connexins. Microelectrode-based intact lens intracellular
      impedance was measured to determine gap junction (GJ) coupling resistance. Lens
      intracellular hydrostatic pressure (HP) was determined using a
      microelectrode/manometer system. Results: Lens opacity and spherical aberration
      were more distinct in AQP0-Htz lenses from FVB than C57 strains. In either
      background, compared to wild type (WT), AQP0-Htz lenses showed decreased Pf
      (approximately 50%), which was restored by transgenic expression of AQP1
      (TgAQP1/AQP0-Htz), but the opacities and differences between FVB and C57
      persisted. Western blotting revealed no change in connexin expression levels.
      However, in C57 AQP0-Htz and TgAQP1/AQP0-Htz lenses, GJ coupling resistance
      decreased approximately 2.8-fold and the HP gradient decreased approximately 1.9
      fold. Increased Pf in TgAQP1/AQP0-Htz did not alter GJ coupling resistance or HP.
      Conclusions: In C57 AQP0-Htz lenses, GJ coupling resistance decreased. HP
      reduction was smaller than the coupling resistance reduction, a reflection of an
      increase in fluid circulation, which is one reason for the less severe cataract
      in C57 than FVB. Overall, our results suggest that AQP0 modulates GJs in the
      presence of BF proteins to maintain lens transparency and homeostasis.

PMID- 29196767
TI  - The Influence of Age and Sex on Ocular Surface Microbiota in Healthy Adults.
AB  - Purpose: A growing body of evidence suggests that the microbiome of the ocular
      surface confers potent immunoregulatory functions and has a key role in the
      physiologic maintenance of healthy eyes and in the pathogenesis of ocular
      diseases. Although the microbiome is known to be affected by age and sex, the
      influence of these factors on ocular surface microbiota in healthy adults remains
      largely unknown. Methods: Ocular surface microbiome samples were obtained from
      the inferior bulbar conjunctiva of 48 young and 42 old adults at Zhongshan
      Ophthalmic Center. Using metagenomic shotgun sequencing, we characterized the sex
      and age-differences in conjunctival microbiome profiles of healthy adults.
      Results: Male and female groups differed only in the beta diversity of bacterial
      communities, while there were significant differences in bacterial composition,
      metabolic functions, and the abundance of antibiotic resistance genes between
      young and old adult groups. Conclusions: Our findings suggest that age and sex
      collectively shape the conjunctival microbiome, and may change the immune
      homeostasis of the ocular surface through alterations of its commensal
      microbiome.

PMID- 29196769
TI  - CTG18.1 Expansion in TCF4 Among African Americans With Fuchs' Corneal Dystrophy.
AB  - Purpose: Studies of Fuchs' dystrophy have largely focused on individuals of
      European origin. Characterization of disease among African Americans is required
      to ensure prognostic factors and therapeutic approaches are applicable across
      diverse patient populations. Methods: We assessed all self-reported black and
      white patients aged older than 40 years at a tertiary care institution with a
      diagnosis of cataract over a 3-year period for concurrent diagnosis of Fuchs'
      dystrophy. Affected patients in a longitudinal cohort were invited to provide a
      blood sample from which we extracted genomic DNA. The CTG18.1 trinucleotide
      repeat length was determined using a two-step, triplet repeat primed PCR
      protocol. Expansion was defined as >40 CTG repeats. Demographic information,
      including race, was documented. Results: Of 59,365 self-reported black and white
      adults who presented for cataract evaluation, the odds ratio of presenting with
      Fuchs' dystrophy among black compared to white patients was 0.6992 (95%
      confidence interval [CI], 0.6210-0.7872). A total of 60 black and 549 white
      patients with Fuchs' corneal dystrophy enrolled in the longitudinal study, of
      which 21 (35.0%) black and 343 (62.5%) white patients demonstrated trinucleotide
      repeat expansion, a significant difference (P = 7.7 * 10-5). In a multivariable
      linear regression model, repeat expansion but not race was significantly
      associated with mean clinical grading of severity. Conclusions: Black patients
      with Fuchs' dystrophy were less likely than white patients to demonstrate CTG18.1
      allele expansion. The data contribute to our understanding of population
      differences in clinical presentation, and highlight the need for considering
      diversity of patient populations in clinical research.

PMID- 29196768
TI  - Macular Atrophy Development and Subretinal Drusenoid Deposits in Anti-Vascular
      Endothelial Growth Factor Treated Age-Related Macular Degeneration.
AB  - Purpose: To explore the association between presence of subretinal drusenoid
      deposits (SDD) at baseline in eyes with neovascular age-related macular
      degeneration (nAMD) with the development of macular atrophy (MA) during anti
      vascular endothelial growth factor (VEGF) therapy. Methods: There were 74 eyes
      without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or
      longer analyzed. At least two image modalities that included spectral-domain
      optical coherence tomography, near-infrared reflectance, fluorescein angiography,
      and color fundus photos were used to assess for SDD presence, phenotype (dot and
      ribbon), and location, neovascularization type, and MA. Logistic regression
      models using generalized estimating equations assessed the association between
      SDD and the development of MA adjusting for age, neovascularization type, and
      choroidal thickness. Results: SDD were present in 46 eyes (63%) at baseline. MA
      developed in 38 eyes (51%) during the mean of 4.7 +/- 1.2 years of follow-up.
      Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95%
      confidence interval [CI] 1.1-8.5, P = 0.0343) more likely to develop MA. Eyes
      with SDD present in the inferior macula and inferior extramacular fields at
      baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than
      eyes without SDD in these locations (95% CI 1.0-8.9, P = 0.0461 and 95% CI 1.3
      32.4, P = 0.0218, respectively). MA development was not associated with a
      specific SDD phenotype. Conclusions: MA frequently developed in eyes during anti
      VEGF treatment. SDD were independently associated with MA development. The
      extension of SDD into the inferior fundus, particularly in the inferior
      extramacular field, conferred higher odds of subsequent MA development.

PMID- 29196770
TI  - Effect of Gravity Acceleration on Choroidal and Retinal Nerve Fiber Layer
      Thickness: A Swept-Source Optical Coherence Tomography Study.
AB  - Purpose: The purpose of this study was to evaluate the effect of gravity
      acceleration on choroidal and retinal nerve fiber layer (RNFL) thickness using
      swept-source optical coherence tomography (SS-OCT). Methods: Thirteen healthy
      volunteers who planned to participate in human centrifuge training as part of the
      flight surgeon selection process enrolled this study. During centrifuge training,
      gravity was gradually increased up to six times that of sea level. All subjects
      underwent complete ophthalmologic examination and three-dimensional wide-scanning
      SS-OCT imaging (DRI OCT-1 Atlantis; Topcon, Tokyo, Japan). Imaging was performed
      before (baseline), immediately after, and 15, 30, and 60 minutes after centrifuge
      training. Changes in choroidal thickness, choroidal volume, retinal thickness,
      and RNFL thickness after centrifuge training were analyzed. Results: Mean
      choroidal thickness significantly and transiently decreased immediately (258.19
      +/- 73.54 MUm, P < 0.001), 15 minutes (258.54 +/- 75.12 MUm, P = 0.001), and 30
      minutes (254.31 +/- 66.92, P = 0.001) after human centrifuge training, relative
      to baseline (273.35 +/- 80.80 MUm). However, the decreased choroidal thickness
      returned to baseline levels 1 hour after centrifuge training (270.12 +/- 71.69
      MUm, P = 0.437). Mean retinal thickness and RNFL thickness were not significantly
      affected by human centrifuge training. In participants who suffered from gravity
      force induced loss of consciousness (G-LOC) during training, the amount of the
      choroidal thickness decrease was larger than in participants who did not
      experience G-LOC. However, because of the small sample size, the difference,
      although large, was not statistically significant. Conclusions: Choroidal
      thickness and volume significantly and transiently decreased after human
      centrifuge training, which might reflect that choroidal perfusion was transiently
      decreased during human centrifuge training. Considering choroidal thickness
      decreased after human centrifuge training, long-term exposure to a high gravity
      environment may lead to ischemic injury to ocular structures.

PMID- 29196772
TI  - Correlation of cue-locked FRN and feedback-locked FRN in the auditory monetary
      incentive delay task.
AB  - Reflecting the discrepancy between received and predicted outcomes, the reward
      prediction error (RPE) plays an important role in learning in a dynamic
      environment. A number of studies suggested that the feedback-related negativity
      (FRN) component of an event-related potential, known to be associated with
      unexpected outcomes, encodes RPEs. While FRN was clearly shown to be sensitive to
      the probability of outcomes, the effect of outcome magnitude on FRN remains to be
      further clarified. In studies on the neural underpinnings of reward anticipation
      and outcome evaluation, a monetary incentive delay (MID) task proved to be
      particularly useful. We investigated whether feedback-locked FRN and cue-locked
      dN200 responses recorded during an auditory MID task were sensitive to the
      probability and magnitude of outcomes. The cue-locked dN200 is associated with
      the update of information about the magnitude of prospective outcomes. Overall,
      we showed that feedback-locked FRN was modulated by both the magnitude and the
      probability of outcomes during an auditory version of MID task, whereas no such
      effect was found for cue-locked dN200. Furthermore, the cue-locked dN200, which
      is associated with the update of information about the magnitude of prospective
      outcomes, correlated with the standard feedback-locked FRN, which is associated
      with a negative RPE. These results further expand our knowledge on the interplay
      between the processing of predictive cues that forecast future outcomes and the
      subsequent revision of these predictions during outcome delivery.

PMID- 29196773
TI  - Effects of contact-based mental illness stigma reduction programs: age, gender,
      and Asian, Latino, and White American differences.
AB  - PURPOSE: Mental illness stigma disproportionately affects help seeking among
      youth, men, and ethnic minorities. As part of a comprehensive statewide
      initiative to reduce mental illness stigma and discrimination in California, a
      broad set of contact-based educational programs were widely disseminated. This
      study examined whether the effects of contact-based educational programs varied
      depending on the age, gender, and race-ethnicity of participants. METHODS:
      Participants (N = 4122) attended a contact-based educational program that was
      delivered as part of the statewide initiative to reduce mental illness stigma and
      discrimination. Self-administered surveys assessing beliefs, attitudes, and
      intentions toward mental illnesses and treatment were conducted immediately
      before and after participation in contact-based educational programs. RESULTS:
      Participant age, gender, and race-ethnicity significantly moderated pre-post
      changes in mental illness stigma. Although all groups exhibited significant pre
      post changes across most of the stigma domains assessed, young adults, females,
      and Asian and Latino American participants reported larger improvements compared
      to older adults, males, and Whites, respectively. CONCLUSIONS: Findings suggest
      that contact-based educational programs can achieve immediate reductions in
      mental illness stigma across a variety of sociodemographic groups and may
      particularly benefit young adults and racial-ethnic minorities. Further research
      is needed to assess whether contact-based educational programs can sustain longer
      term changes and aid in the reduction of disparities in mental illness stigma and
      treatment.

PMID- 29196771
TI  - The interrelation of osteoarthritis and diabetes mellitus: considering the
      potential role of interleukin-10 and in vitro models for further analysis.
AB  - INTRODUCTION: Today, not only the existence of an interrelation between
      obesity/adipositas and osteoarthritis (OA) but also the association of OA and
      diabetes mellitus (DM) are widely recognized. Nevertheless, shared influence
      factors facilitating OA development in DM patients still remain speculative up
      until now. To supplement the analysis of clinical data, appropriate in vitro
      models could help to identify shared pathogenetic pathways. Informative in vitro
      studies could later be complemented by in vivo data obtained from suitable animal
      models. MATERIALS AND METHODS: Therefore, this detailed review of available
      literature was undertaken to discuss and compare the results of currently
      published in vitro studies focusing on the interrelation between OA, the
      metabolic syndrome and DM and to propose models to further study the molecular
      pathways. RESULTS: The survey of literature presented here supports the
      hypothesis that the pathogenesis of OA in DM is based on imbalanced molecular
      pathways with a putative crucial role of antiinflammatory cytokines such as IL
      10. CONCLUSION: Future development of versatile micro-scaled in vitro models such
      as combining DM and OA on chip could allow the identification of common
      pathogenetic pathways and might help to develop novel therapeutic strategies.

PMID- 29196774
TI  - [Suitability of computer-assisted femoral intramedullary nailing for control of
      torsion and length : Systematic review of clinical studies].
AB  - BACKGROUND: Despite promising results in experimental studies, computer-assisted
      femoral intramedullary nailing has not become established in the clinical
      practice for most orthopedic surgeons. The purpose of this study was to evaluate
      the advantages and disadvantages of computer-assisted reduction and nailing of
      femoral fractures as reported in clinical studies. MATERIAL AND METHODS: A
      systematic analysis of the available literature on the clinical application of
      computer-assisted femoral intramedullary nailing (Pubmed, Cochrane library and
      Embase) was carried out. Studies published up to May 2017 were included. RESULTS:
      A total of three articles were included in this meta-analysis. All studies showed
      a relevant increase in total operating time and radiation exposure time with the
      use of computer-assisted femoral intramedullary nailing. The clinical results for
      computer-assisted nailing with respect to femoral torsion and length tended to be
      slightly better but the results were very heterogeneous. CONCLUSION: Our analysis
      could show that computer-assisted femoral intramedullary nailing is clinically
      feasible but the operative and fluoroscopy time needed are high and the reported
      postoperative results for femoral length and torsion were very heterogeneous.
      Further comparative studies are needed in the future.

PMID- 29196775
TI  - A health economic simulation model for the clinical management of osteoporosis.
AB  - : The objective was to estimate the burden of osteoporosis in Sweden based on
      current clinical practice and the cost-effectiveness of improvements in the
      management of osteoporosis over the clinical management compared to current
      clinical practice. Results showed that better compliance to treatment guidelines
      is associated with better projected outcomes and cost-savings. INTRODUCTION: The
      purpose of this study is to estimate the burden of osteoporosis in Sweden based
      on current clinical practice and the cost-effectiveness of improvements in the
      management of osteoporosis over the clinical management compared to current
      clinical practice. METHODS: The analysis was carried out using a model that
      simulates the individual patients considered for pharmacological treatment during
      1 year and their projected osteoporosis treatment pathway, quality-adjusted life
      years (QALYs) and costs over their remaining lifetime. All patients regardless of
      treatment or no treatment were simulated. Information on current management of
      osteoporosis in terms of patient characteristics and treatment patterns were
      derived from a Swedish osteoporosis research database based on national registers
      and patient records. Current (standard) clinical management was compared with
      alternative scenarios mirroring Swedish treatment guidelines. RESULTS: The
      national burden in terms of lost QALYs was estimated at 14,993 QALYs and the
      total economic cost at ?776M. Scenario analyses showed that 382-3864 QALYs could
      be gained at a cost/QALY ranging from cost-saving to ?31368, depending on the
      scenario. The margin of investment, i.e. the maximum amount that could be
      invested in the healthcare system to achieve these improvements up to the limit
      of the willingness to pay/QALY, was estimated at ?199M on a population level
      (?3,634/patient). CONCLUSIONS: The analysis showed that better compliance to
      treatment guidelines is associated with better projected outcomes and cost
      savings. From a cost-effectiveness perspective, there is also considerable room
      for investment to achieve these improvements in the management of osteoporosis.

PMID- 29196776
TI  - [Anticoagulation and antithombotic therapy].

PMID- 29196777
TI  - Freiburg Neuropathology Case Conference : Intradural, Intramedullary Mass Lesion
      in a 66-year-old Patient.

PMID- 29196778
TI  - Disappearing Leukoencephalopathy : A Case of Relapsing-Remitting Intravascular
      Large B-Cell Lymphoma with Transient Spontaneous Radiographic Regression.

PMID- 29196779
TI  - Restriction enzyme-mediated insertional mutagenesis: an efficient method of
      Rosellinia necatrix transformation.
AB  - Rosellinia necatrix: causing root rot disease is a very destructive pathogen of
      woody plants and is responsible for yield losses to a large number of fruit
      trees. The genetic analysis of this pathogen has not been picked up because of
      difficulty in generating mutations in Rosellinia necatrix for many reasons. A
      number of methods have been proposed for inducing mutations in Rosellinia
      necatrix but none of them proved worth because of very low transformation
      efficiencies. Here, we propose an efficient method for Rosellinia necatrix
      protoplast production, where protoplasts in the tune of 107 per ml can be easily
      generated. We also propose a restriction enzyme-mediated integration (REMI)-based
      methods for efficient transformation of Rosellinia necatrix. In the present
      study, an approximate of 800 transformants was obtained from 5 MUg of linearized
      plasmid. Out of 47 single spored transformants analyzed, only 33 showed
      hygromycin gene amplification using PCR and only 19 transformants showed single
      gene integration in southern hybridization, which accounted for single gene
      integration percentage of 42%, highest amongst all the previous reports on
      Rosellinia necatrix transformations. Some of the transformants studied for
      pathogenicity phenotype also showed a marked reduction in pathogenicity. Thus, in
      the present investigation, 42% single gene integrations among the transformed
      colonies can be considered as excellent transformation efficiency.

PMID- 29196780
TI  - Scientific Abstracts 8th Phoenix Fetal Cardiology Symposium October 27-31, 2017 :
      Sponsored by Phoenix Children's Hospital, Phoenix, AZ.

PMID- 29196781
TI  - Acute Pulmonary Vasodilator Testing and Long-Term Clinical Course in Segmental
      Pulmonary Vascular Disease.
AB  - Results of acute pulmonary vasodilator testing (AVT) and the outcome of medical
      therapy have not been described in patients with segmental pulmonary vascular
      disease (SPVD). We sought to compare the pulmonary vasodilatory effects of
      oxygen, oxygen with nitric oxide, and diltiazem, and to describe the clinical
      course of patients with SPVD and pulmonary hypertension. A retrospective review
      of 16 patients with pulmonary hypertension and SPVD involving 2-3 major lung
      segments who underwent AVT between January 2000 and December 2015 was performed.
      Baseline hemodynamic measurements were obtained with patients breathing <= 30%
      oxygen. AVT was performed using 100% oxygen, 100% oxygen with 20 ppm nitric
      oxide, 21-35% oxygen, and 21-35% oxygen with intravenous diltiazem. The events
      associated with their long-term care were described. Nine of 16 patients were
      acutely responsive during AVT using the Sitbon criteria. The change in mean
      pulmonary artery pressure with oxygen or oxygen with nitric oxide (19 +/- 12
      mmHg) was significantly greater than the change with diltiazem (7 +/- 5 mmHg).
      Pulmonary vasodilator therapy was initiated or escalated after AVT in 12
      patients. Five patients subsequently experienced a decrease in mean pulmonary
      artery pressure or normalization in B-type natriuretic peptide. Three patients
      experienced adverse events associated with therapy. The actuarial survival was
      94% over a period of 1-20 years. This study suggests that AVT can be used to
      identify patients with SPVD who are reactive to oxygen, oxygen with nitric oxide,
      and diltiazem. Clinical improvement was temporally associated with pulmonary
      vasodilator therapy in some patients with few adverse effects.

PMID- 29196782
TI  - Adapting to insulin resistance in obesity: role of insulin secretion and
      clearance.
AB  - AIMS/HYPOTHESIS: The aim of this study was to quantify the relative contributions
      of increased insulin secretion rate (ISR) and decreased insulin clearance rate
      (ICR) in the compensatory hyperinsulinaemia characteristic of insulin-resistant
      individuals without diabetes. METHODS: Obese (BMI >=30 kg/m2) individuals without
      diabetes (n = 91) were identified from a registry of volunteers. Volunteers
      underwent the following measurements: oral glucose tolerance; insulin resistance
      (steady-state plasma glucose [SSPG] concentration during the insulin suppression
      test [IST]); ISR (using the graded glucose infusion test [GGIT]); and ICR (using
      the IST and GGIT). Participants were stratified into tertiles based on SSPG
      concentration: SSPG-1(insulin-sensitive); SSPG-2 (intermediate); and SSPG-3
      (insulin-resistant). RESULTS: There were no differences in BMI and waist
      circumference among the SSPG tertiles. Serum alanine aminotransferase
      concentrations were higher in the SSPG-2 and SSPG-3 groups compared with the SSPG
      1 group (p = 0.02). Following an oral glucose challenge, there was a progressive
      increase in the total integrated insulin response from the most insulin-sensitive
      to the most insulin-resistant tertiles (p < 0.001). Following intravenous
      glucose, the SSPG-3 group had significantly greater integrated glucose (median
      [interquartile range], 32.9 [30.8-36.3] mmol/l * h) and insulin responses (1711
      [1476-2223] mmol/l * h) compared with the SSPG-1 group (30.3 [28.8-32.9] mmol/l *
      h, p = 0.04, and 851 [600-1057] pmol/l * h, p < 0.001, respectively).
      Furthermore, only the SSPG-3 group had significant changes in both ISR and ICR (p
      < 0.001). In the SSPG-2 group, only the ICR was significantly decreased compared
      with the SSPG-1 group. Therefore, ICR progressively declined during the IST with
      increasing insulin resistance (SSPG-1, 0.48 [0.41-0.59]; SSPG-2, 0.43 [0.39
      0.50]; SSPG-3, 0.34 [0.31-0.40]). CONCLUSIONS/INTERPRETATION: While both
      increases in ISR and decreases in ICR compensate for insulin resistance,
      decreases in ICR may provide the first adaptation to decreased insulin
      sensitivity.

PMID- 29196783
TI  - Combinatorial detection of autoreactive CD8+ T cells with HLA-A2 multimers: a
      multi-centre study by the Immunology of Diabetes Society T Cell Workshop.
AB  - AIMS/HYPOTHESIS: Validated biomarkers are needed to monitor the effects of immune
      intervention in individuals with type 1 diabetes. Despite their importance, few
      options exist for monitoring antigen-specific T cells. Previous reports described
      a combinatorial approach that enables the simultaneous detection and
      quantification of multiple islet-specific CD8+ T cell populations. Here, we set
      out to evaluate the performance of a combinatorial HLA-A2 multimer assay in a
      multi-centre setting. METHODS: The combinatorial HLA-A2 multimer assay was
      applied in five participating centres using centralised reagents and blinded
      replicate samples. In preliminary experiments, samples from healthy donors were
      analysed using recall antigen multimers. In subsequent experiments, samples from
      healthy donors and individuals with type 1 diabetes were analysed using beta cell
      antigen and recall antigen multimers. RESULTS: The combinatorial assay was
      successfully implemented in each participating centre, with CVs between replicate
      samples that indicated good reproducibility for viral epitopes (mean %CV = 33.8).
      For beta cell epitopes, the assay was very effective in a single-centre setting
      (mean %CV = 18.4), but showed sixfold greater variability across multi-centre
      replicates (mean %CV = 119). In general, beta cell antigen-specific CD8+ T cells
      were detected more commonly in individuals with type 1 diabetes than in healthy
      donors. Furthermore, CD8+ T cells recognising HLA-A2-restricted insulin and
      glutamate decarboxylase epitopes were found to occur at higher frequencies in
      individuals with type 1 diabetes than in healthy donors.
      CONCLUSIONS/INTERPRETATION: Our results suggest that, although combinatorial
      multimer assays are challenging, they can be implemented in multiple
      laboratories, providing relevant T cell frequency measurements. Assay
      reproducibility was notably higher in the single-centre setting, suggesting that
      biomarker analysis of clinical trial samples would be most successful when assays
      are performed in a single laboratory. Technical improvements, including further
      standardisation of cytometry platforms, will likely be necessary to reduce assay
      variability in the multi-centre setting.

PMID- 29196784
TI  - PARP1 protects from benzo[a]pyrene diol epoxide-induced replication stress and
      mutagenicity.
AB  - Poly(ADP-ribosyl)ation (PARylation) is a complex and reversible posttranslational
      modification catalyzed by poly(ADP-ribose)polymerases (PARPs), which orchestrates
      protein function and subcellular localization. The function of PARP1 in genotoxic
      stress response upon induction of oxidative DNA lesions and strand breaks is
      firmly established, but its role in the response to chemical-induced, bulky DNA
      adducts is understood incompletely. To address the role of PARP1 in the response
      to bulky DNA adducts, we treated human cancer cells with benzo[a]pyrene 7,8
      dihydrodiol-9,10-epoxide (BPDE), which represents the active metabolite of the
      environmental carcinogen benzo[a]pyrene [B(a)P], in nanomolar to low micromolar
      concentrations. Using a highly sensitive LC-MS/MS method, we revealed that BPDE
      induces cellular PAR formation in a time- and dose-dependent manner.
      Consistently, PARP1 activity significantly contributed to BPDE-induced genotoxic
      stress response. On one hand, PARP1 ablation rescued BPDE-induced NAD+ depletion
      and protected cells from BPDE-induced short-term toxicity. On the other hand,
      strong sensitization effects of PARP inhibition and PARP1 ablation were observed
      in long-term clonogenic survival assays. Furthermore, PARP1 ablation
      significantly affected BPDE-induced S- and G2-phase transitions. Together, these
      results point towards unresolved BPDE-DNA lesions triggering replicative stress.
      In line with this, BPDE exposure resulted in enhanced formation and persistence
      of DNA double-strand breaks in PARP1-deficient cells as evaluated by microscopic
      co-localization studies of 53BP1 and gammaH2A.X foci. Consistently, an HPRT
      mutation assay revealed that PARP inhibition potentiated the mutagenicity of
      BPDE. In conclusion, this study demonstrates a profound role of PARylation in
      BPDE-induced genotoxic stress response with significant functional consequences
      and potential relevance with regard to B[a]P-induced cancer risks.

PMID- 29196785
TI  - Improvement in physician pain perception with using pain scales.
AB  - BACKGROUND AND AIMS: Acute pain is the most common reason for visits to the
      emergency department (ED). The underuse of analgesics occurs in a large
      proportion of ED patients. The physician's accurate assessment of patients' pain
      is a key element to improved pain management. The purpose of this study was to
      assess if physicians' perception of pain can improve with looking at the pain
      score of the patient marked on VAS. STUDY DESIGN: This was a single-center, cross
      sectional prospective observational study, that took place in an academic ED.
      METHODS: All adult ED patients presenting with a painful condition were enrolled
      to the study. In the first phase of the study, the physician rated his/her
      opinion about the patient's pain on a 100 mm VAS, in a blinded fashion to the
      patient's pain score. In the second phase, the physician rated his/her opinion
      after looking at the pain scale marked by patient. RESULTS: 587 patients (295, in
      first and 292, in second phase) were enrolled. The groups were not statistically
      different for demographic data. The physician's perception of pain was lower than
      the patient's pain score at both phases of the study. Insight of the patient's
      pain score on VAS increased the physician's pain perception significantly (p =
      0.03). During the second phase, physicians ordered significantly more analgesic
      medications to the patients (p = 0.03). CONCLUSION: The physicians' perception of
      the patients' pain differs significantly from the pain that the patient is
      experiencing. VAS helps to bring the physicians impression of pain perception to
      the level of pain that the patient is actually experiencing and resulted in
      ordering more analgesics to the patients. Implementation of a pain assessment
      tool can raise the physician's perception of the pain and may improve pain
      management practices and patient satisfaction.

PMID- 29196786
TI  - Increased heterologous production of the antitumoral polyketide mithramycin A by
      engineered Streptomyces lividans TK24 strains.
AB  - Mithramycin A is an antitumor compound used for treatment of several types of
      cancer including chronic and acute myeloid leukemia, testicular carcinoma,
      hypercalcemia and Paget's disease. Selective modifications of this molecule by
      combinatorial biosynthesis and biocatalysis opened the possibility to produce
      mithramycin analogues with improved properties that are currently under
      preclinical development. The mithramycin A biosynthetic gene cluster from
      Streptomyces argillaceus ATCC12956 was cloned by transformation assisted
      recombination in Saccharomyces cerevisiae and heterologous expression in
      Streptomyces lividans TK24 was evaluated. Mithramycin A was efficiently produced
      by S. lividans TK24 under standard fermentation conditions. To improve the yield
      of heterologously produced mithramycin A, a collection of derivative strains of
      S. lividans TK24 were constructed by sequential deletion of known potentially
      interfering secondary metabolite gene clusters using a protocol based on the
      positive selection of double crossover events with blue pigment indigoidine
      producing gene. Mithramycin A production was evaluated in these S. lividans
      strains and substantially improved mithramycin A production was observed
      depending on the deleted gene clusters. A collection of S. lividans strains
      suitable for heterologous expression of actinomycetes secondary metabolites were
      generated and efficient production of mithramycin A with yields close to 3 g/L,
      under the tested fermentation conditions was achieved using these optimized
      collection of strains.

PMID- 29196787
TI  - Erythritol as sweetener-wherefrom and whereto?
AB  - Erythritol is a naturally abundant sweetener gaining more and more importance
      especially within the food industry. It is widely used as sweetener in calorie
      reduced food, candies, or bakery products. In research focusing on sugar
      alternatives, erythritol is a key issue due to its, compared to other polyols,
      challenging production. It cannot be chemically synthesized in a commercially
      worthwhile way resulting in a switch to biotechnological production. In this
      area, research efforts have been made to improve concentration, productivity, and
      yield. This mini review will give an overview on the attempts to improve
      erythritol production as well as their development over time.

PMID- 29196788
TI  - Quantification of the catalytic performance of C1-cellulose-specific lytic
      polysaccharide monooxygenases.
AB  - Lytic polysaccharide monooxygenases (LPMOs) have recently been shown to
      significantly enhance the degradation of recalcitrant polysaccharides and are of
      interest for the production of biochemicals and bioethanol from plant biomass.
      The copper-containing LPMOs utilize electrons, provided by reducing agents, to
      oxidatively cleave polysaccharides. Here, we report the development of a beta
      glucosidase-assisted method to quantify the release of C1-oxidized gluco
      oligosaccharides from cellulose by two C1-oxidizing LPMOs from Myceliophthora
      thermophila C1. Based on this quantification method, we demonstrate that the
      catalytic performance of both MtLPMOs is strongly dependent on pH and
      temperature. The obtained results indicate that the catalytic performance of
      LPMOs depends on the interaction of multiple factors, which are affected by both
      pH and temperature.

PMID- 29196789
TI  - Prediction of functional recovery after primary PCI using the estimate of
      myocardial salvage in gated SPECT early after acute myocardial infarction.
AB  - PURPOSE: Primary percutaneous coronary intervention (PCI) in acute myocardial
      infarction (AMI) aims to achieve myocardial salvage (MS). Because the reference
      method for measuring MS requires myocardial perfusion imaging (MPI) after tracer
      injection before PCI, alternative approaches have been proposed, but none has
      gained wide acceptance. Gated SPECT MPI can assess infarct size (IS), but can
      also show myocardial stunning. Thus, we compared functional and perfusion
      abnormalities early after AMI to estimate MS, and to predict left ventricular
      ejection fraction (LVEF) recovery at follow-up. METHODS: We studied 120 patients
      with AMI. Gated SPECT MPI was performed early (before hospital discharge) and at
      6 months after AMI to measure IS, MS and functional outcome. MS was defined as
      the difference between the number of segments with abnormal thickening (i.e. the
      stunned area or area at risk) and the number of segments with abnormal perfusion
      (i.e. the final IS), expressed as a percentage of the total number of segments in
      the AHA model. LVEF was calculated using quantitative gated SPECT. RESULTS: The
      area at risk was 40 +/- 25%, IS was 17.3 +/- 16% and MS was 22 +/- 19%. Early
      LVEF was 46.6 +/- 11.6% and late LVEF was 51.4 +/- 11.6%, with 54 patients
      showing at least an increase in LVEF of more than 5 units. ROC analysis showed
      that MS was able to predict LVEF recovery with an area under the curve (AUC) of
      0.79 (p < 0.0001), and using a cut off >23% detected LVEF recovery with 74%
      sensitivity and 71% specificity. Conversely, IS was associated with an AUC 0.53
      (not significant). CONCLUSION: MS assessed by a single early gated SPECT MPI
      study can accurately predict LVEF evolution after primary PCI for AMI.

PMID- 29196790
TI  - 2nd Symposium on Advances in Cancer Immunology and Immunotherapy, December 15-17,
      2016, Athens, Greece.
AB  - This is the 2nd Symposium of a series organized annually. It aims to integrate
      tumor immunology basic research with results from most recent clinical trials
      based on the use of anti-cancer agents targeting immune system components.

PMID- 29196791
TI  - Comparison of dual mobility cup and other surgical construts used for three
      hundred and sixty two first time hip revisions due to recurrent dislocations:
      five year results from Lithuanian arthroplasty register.
AB  - PURPOSE: Recently, there has been increasing interest in the use of dual mobility
      systems in the treatment of hip instability. The aim of this study was to
      investigate the re-revision rate of dual mobility cup compared to different
      surgical concepts when used for first-time hip revisions due to recurrent
      dislocations. METHODS: The data were derived from the Lithuanian Arthroplasty
      Register. For survival analysis, we used both re-revision for all reasons and for
      dislocations as an end-point. Cox proportional hazards models were used to
      analyze the influence of various covariates (age, gender, and implant concept).
      RESULTS: A total of 1388 revisions were recorded from 2011 to 2015, of which 362
      were performed due to recurrent dislocation. Of the revisions, 247 were performed
      using dual mobility cups, while 115 were performed using a variety of other
      surgical constructs including constrained acetabular cups, conventional cups,
      femoral head exchanges, stem exchanges or anti-luxation rings. There were 27 re
      revisions of which 15 were for additional dislocations. There were only 2% re
      revisions due to dislocation with dual mobility vs 9% when using other surgical
      constructs. Cox regression adjusting for age and gender showed that in the short
      term, dual mobility cup had a lower risk of revision due to dislocation as well
      as for all reasons compared to the other surgical constructs. CONCLUSION: In
      revision of total hip arthroplasties for dislocation, significantly lower short
      term re-revision rate was observed for patients revised with dual mobility cup.

PMID- 29196792
TI  - The 10 false beliefs in adult critical care nephrology.

PMID- 29196795
TI  - Can Rice (Oryza sativa) Mitigate Pesticides and Nutrients in Agricultural Runoff?
AB  - Phytoremediation of nutrients and pesticides in runoff is a growing conservation
      effort, particularly in agriculturally intensive areas such as the lower
      Mississippi River Valley. In the current study, rice (Oryza sativa) was examined
      for its mitigation capacity of nitrogen, phosphorus, diazinon, and permethrin.
      Twenty-two high density polyethylene circular containers (56 cm x 45 cm) were
      used as mesocosms, with 12 mesocosms planted with rice and 10 mesocosms remaining
      unvegetated. Mesocosms were hydraulically connected and arranged in a series of
      two, with each system providing a 4 h hydraulic retention time (HRT) for a total
      system retention time of 8 h. Two treatments (RICE/RICE and RICE/BARE) of four
      replicates each were utilized, with three replicates of controls (BARE/BARE).
      Systems with RICE/RICE (8 h HRT) significantly reduced diazinon (p = 0.0126), cis
      permethrin (p = 0.0442), filtered orthophosphate (p = 0.0058), and total
      orthophosphate (p = 0.0123) compared to control systems. No significant
      differences were noted for trans-permethrin, nitrate, or ammonium. Results
      indicate promise in phytoremediation of agricultural runoff by rice. If further
      studies reveal contaminants are not transferred into seeds, then rice could
      potentially serve as both a remediation tool and food source in countries facing
      agricultural pollution challenges.

PMID- 29196794
TI  - Ultrasound-guided or landmark techniques for central venous catheter placement in
      critically ill children.
AB  - PURPOSE: To assess whether ultrasound guidance improves central venous catheter
      placement outcomes compared to the landmark technique in critically ill children.
      METHODS: A prospective multicentre observational study was carried out in 26
      paediatric intensive care units over 6 months. Children 0-18 years old who
      received a temporary central venous catheter, inserted using either ultrasound or
      landmark techniques, were eligible. The primary outcome was the first-attempt
      success rate. Secondary outcomes included overall placement success, number of
      puncture attempts, number of procedures requiring multiple punctures (> 3
      punctures), number of procedures requiring punctures at more than one vein site
      and immediate mechanical complications. To account for potential confounding
      factors, we used propensity scores. Our primary analysis was based on 1:1
      propensity score matching. The association between cannulation technique and
      outcomes in the matched cohort was estimated using generalized estimating
      equations and mixed-effects models to account for patient-level and hospital
      level confounders. RESULTS: Five hundred central venous catheter-placement
      procedures involving 354 patients were included. Ultrasound was used for 323
      procedures, and the landmark technique was used for 177. Two hundred and sixty
      six procedures were matched (133 in the ultrasound group and 133 in the landmark
      group). Ultrasound was associated with an increase in the first-attempt success
      rate [46.6 vs. 30%, odds ratio 2.09 (1.26-3.46); p < 0.001], a reduced number of
      puncture attempts [2 (1-3) vs. 2 (1-4), B coefficient - 0.51 (95% confidence
      interval - 1.01 to - 0.03), p = 0.035], and fewer overall mechanical
      complications [12 vs. 22.5%, odds ratio 0.47 (95% confidence interval 0.24-0.91),
      p = 0.025] in the matched cohort. The number of puncture attempts was the main
      factor associated with overall complications. CONCLUSIONS: Compared with the
      landmark technique, ultrasound guidance was associated with an increased first
      attempt success rate, a reduced number of puncture attempts, and fewer
      complications during central venous catheter placement in critically ill
      children.

PMID- 29196798
TI  - [Correction: Hyaluronic acid gels for pressure regulation in glaucoma treatment].

PMID- 29196796
TI  - Increased herpes zoster risk associated with poor HLA-A immediate early 62
      protein (IE62) affinity.
AB  - Around 30% of individuals will develop herpes zoster (HZ), caused by the
      varicella zoster virus (VZV), during their life. While several risk factors for
      HZ, such as immunosuppressive therapy, are well known, the genetic and molecular
      components that determine the risk of otherwise healthy individuals to develop HZ
      are still poorly understood. We created a computational model for the Human
      Leukocyte Antigen (HLA-A, -B, and -C) presentation capacity of peptides derived
      from the VZV Immediate Early 62 (IE62) protein. This model could then be applied
      to a HZ cohort with known HLA molecules. We found that HLA-A molecules with poor
      VZV IE62 presentation capabilities were more common in a cohort of 50 individuals
      with a history of HZ compared to a nationwide control group, which equated to a
      HZ risk increase of 60%. This tendency was most pronounced for cases of HZ at a
      young age, where other risk factors are less prevalent. These findings provide
      new molecular insights into the development of HZ and reveal a genetic
      predisposition in those individuals most at risk to develop HZ.

PMID- 29196793
TI  - Correction to: Incidence of severe sepsis and septic shock in German intensive
      care units: the prospective, multicentre INSEP study.
AB  - The members of the SepNet Critical Care Trials Group were provided in such a way
      that they could not be indexed as collaborators on PubMed. The publisher
      apologizes for this error and is pleased to list the members of the group here.

PMID- 29196797
TI  - Sorting nexin 3 mutation impairs development and neuronal function in
      Caenorhabditis elegans.
AB  - The sorting nexins family of proteins (SNXs) plays pleiotropic functions in
      protein trafficking and intracellular signaling and has been associated with
      several disorders, namely Alzheimer's disease and Down's syndrome. Despite the
      growing association of SNXs with neurodegeneration, not much is known about their
      function in the nervous system. The aim of this work was to use the nematode
      Caenorhabditis elegans that encodes in its genome eight SNXs orthologs, to
      dissect the role of distinct SNXs, particularly in the nervous system. By
      screening the C. elegans SNXs deletion mutants for morphological, developmental
      and behavioral alterations, we show here that snx-3 gene mutation leads to an
      array of developmental defects, such as delayed hatching, decreased brood size
      and life span and reduced body length. Additionally, ?snx-3 worms present
      increased susceptibility to osmotic, thermo and oxidative stress and distinct
      behavioral deficits, namely, a chemotaxis defect which is independent of the
      described snx-3 role in Wnt secretion. ?snx-3 animals also display abnormal
      GABAergic neuronal architecture and wiring and altered AIY interneuron structure.
      Pan-neuronal expression of C. elegans snx-3 cDNA in the ?snx-3 mutant is able to
      rescue its locomotion defects, as well as its chemotaxis toward isoamyl alcohol.
      Altogether, the present work provides the first in vivo evidence of the SNX-3
      role in the nervous system.

PMID- 29196799
TI  - 3C-PCR: a novel proximity ligation-based approach to phase chromosomal
      rearrangement breakpoints with distal allelic variants.
AB  - Recent advances in molecular cytogenetics highlight the importance of noncoding
      structural variation in human disease. Genomic rearrangements can disrupt
      chromatin architecture, leading to long-range alterations in gene expression.
      With increasing ability to assess distal gene dysregulation comes new challenges
      in clinical interpretation of rearrangements. While haplotyping methods to
      determine compound heterozygosity in a single gene with two pathogenic variants
      are established, such methods are insufficient for phasing larger distances
      between a pathogenic variant and a genomic rearrangement breakpoint. Herein, we
      present an inexpensive and efficient proximity ligation-based method called 3C
      PCR for phasing chromosomal rearrangement breakpoints with distal allelic
      variants. 3C-PCR uses canonical chromosome conformation capture (3C) libraries
      for targeted distal phasing by implementing a novel nested PCR strategy with
      primers anchored across the rearrangement breakpoints and subsequent Sanger
      sequencing. As a proof of concept, 3C-PCR was used to phase a highly variable
      region 1.3 Mb upstream of a chromosomal rearrangement breakpoint in a balanced
      translocation. We found that the nested PCR approach amplified the derivative
      chromosome substrate exclusively and identified the same haplotype by Sanger
      sequencing reliably. Given its efficacy and versatility, 3C-PCR is ideal for use
      in phasing chromosomal rearrangement breakpoints with allelic variants located at
      a genomic distance over a megabase.

PMID- 29196800
TI  - Effects of mating on host selection by female small white butterflies Pieris
      rapae (Lepidoptera: Pieridae).
AB  - Mating might significantly affect the host selection behaviors of phytophagous
      insects. Here, we investigated the post-mating changes in behavioral and antennal
      responses of Pieris rapae (Lepidoptera: Pieridae) females to host plant
      volatiles. In two-choice bioassays using artificial plant models, mated females
      visited the model scented with synthetic blends (15-, 9-, or 6-components) of
      cabbage plant volatiles more frequently than the unscented control, whereas
      virgin females did not exhibit this preference. Because single compounds and the
      3-component blend did not induce preferential visiting, mated females apparently
      utilized complex odor blends as their host-finding cue. Moreover, 2- to 4-day-old
      mated females visited the models, scented and unscented, more frequently than did
      their virgin counterparts. Therefore, mating enhanced the host-finding behavior
      of young females and their responsiveness to plant volatiles. Gas chromatography
      electroantennographic detector analysis revealed that eight of the 15 compounds
      in the cabbage plant volatiles elicited responses from female antennae. However,
      post-mating and age-dependent changes in antennal responses were not detected.
      Because female peripheral (antennal) sensitivity to volatiles remained
      practically unchanged after emergence, post-mating changes in host selection
      might be attributed to changes in the central nervous system.

PMID- 29196801
TI  - Better understanding of publishing practices and indexing of target journals is
      essential.

PMID- 29196802
TI  - Study of serial serum myeloid-related protein 8/14 as a sensitive biomarker in
      Takayasu arteritis: a single centre study.
AB  - The aim of the study was to explore utility of serial serum myeloid-related
      protein 8/14 (MRP8/14) as a biomarker of clinical disease activity and
      angiographic progression in Takayasu arteritis (TA). Serum MRP8/14 levels were
      assayed by commercial ELISA for 85 TA patients and 24 healthy controls at
      baseline, and for 56 and 21 TA patients during follow-up visits R1 and R2,
      respectively. Disease was categorised as active, indeterminate and stable
      according to Indian Takayasu Arteritis score (ITAS 2010), ITAS-A(CRP) and
      angiography. Patients were divided into responders and non-responders/relapsers
      based on treatment response. Non-parametric tests were used for inter-group
      comparisons at baseline and during follow-up time points. Generalised Estimating
      Equation was used to study association between changes in serial MRP8/14 levels
      and disease activity. At baseline, median MRP8/14 levels were higher in patients
      with TA than healthy controls [7353 (4524 to11283) vs 4896 (3194 to 8474.5)
      ng/ml, p = 0.011]. Patients with active disease had higher levels [8552 (5463
      12488)] than stable disease [5292.5 (3140.5-7310)], p = 0.002, and healthy
      controls [4896 (3194-8474.5)], p = 0.001. Changes in serial MRP8/14 level were
      associated with changes in disease activity, independent of steroid dose, p =
      0.000. At R1, MRP 8/14 levels were lower than baseline in responders (n = 38)
      [9146.0 (6296.8-13693.8) vs 6501 (4314.8-8304.5), p = 0.004], but did not change
      in non-responders/relapsers (n = 14) [6693.5(4210.8-10516.3) vs 7755.0(5342
      10741.0), p = 0.42]. Similar trend was observed at R2. MRP8/14 levels increased
      during follow-up in 66% and 26.3% of angiographic progressors and non
      progressors, respectively. MRP8/14 in TA may act as a novel biomarker with
      prognostic implications.

PMID- 29196803
TI  - Pulmonary function and high-resolution computed tomography examinations among
      offshore drill floor workers.
AB  - PURPOSE: The aim of this study was to assess short-term changes in pulmonary
      function in drill floor workers currently exposed to airborne contaminants
      generated as a result of drilling offshore. We also aimed to study the prevalence
      of pulmonary fibrosis using high-resolution computed tomography (HRCT) scans of
      another group of previously exposed drill floor workers. METHODS: Pulmonary
      function was measured before and after a 14-day work period in a follow-up study
      of 65 drill floor workers and 65 referents. Additionally, 57 other drill floor
      workers exposed to drilling fluids during the 1980s were examined with HRCT of
      the lungs in a cross-sectional study. RESULTS: The drill floor workers had a
      statistically significant decline in forced expiratory volume in 1 s (FEV1)
      across the 14-day work period after adjustment for diurnal variations in
      pulmonary function (mean 90 mL, range 30-140 mL), while the small decline among
      the referents (mean 20 mL, range - 30 to 70 mL) was not of statistical
      significance. Larger declines in FEV1 among drill workers were associated with
      the fewer number of days of active drilling. There were no signs of pulmonary
      fibrosis related to oil mist exposure among the other previously exposed drill
      floor workers. CONCLUSION: After 14 days offshore, a statistically significant
      decline in FEV1 was observed in the drill floor workers, which may not be related
      to oil mist exposure. No pulmonary fibrosis related to oil mist exposure was
      observed.

PMID- 29196805
TI  - Correction to: Abstracts : 29th European Congress of Pathology.
AB  - Due to an error with the registration system, the following abstract was
      regrettably omitted from the Poster Sessions. The abstract should have been
      included as PS-10-021 and displayed on page S166.

PMID- 29196804
TI  - IgG4-related disease: with emphasis on the biopsy diagnosis of autoimmune
      pancreatitis and sclerosing cholangitis.
AB  - In 2011, chronic fibroinflammatory processes occurring simultaneously or
      metachronously in various organs and associated with elevated IgG4 serum levels
      and/or tissue infiltration with IgG4-positive plasma cells have been recognized
      as manifestations of a systemic disorder called IgG4-related disease (IgG4-RD).
      The histologic key findings are lymphoplasmacytic infiltration rich in IgG4
      positive plasma cells combined with storiform fibrosis and obliterative
      phlebitis. Among the organs mainly affected by IgG4-RD are the pancreas and the
      extrahepatic bile ducts. The pancreatic and biliary alterations have been
      described under the terms autoimmune pancreatitis (AIP) and sclerosing
      cholangitis, respectively. These diseases are currently more precisely called
      IgG4-related pancreatitis (or type 1 AIP to distinguish it from type 2 AIP that
      is unrelated to IgG4-RD) and IgG4-related sclerosing cholangitis (IgG4-related
      SC). Clinically and grossly, both diseases commonly imitate pancreatic and
      biliary adenocarcinoma, tumors that are well known for their dismal prognosis. As
      IgG4-RD responds to steroid treatment, making a resection of a suspected tumor
      unnecessary, a biopsy is often required to establish the preoperative diagnosis.
      This review discusses the morphologic spectrum of IgG4-related pancreatitis and
      IgG4-related SC and focuses on the biopsy relevant histologic features for the
      diagnosis and differential diagnosis of these diseases.

PMID- 29196806
TI  - Sensitivity and requirement of improvements of four soybean crop simulation
      models for climate change studies in Southern Brazil.
AB  - Crop growth models have many uncertainties that affect the yield response to
      climate change. Based on that, the aim of this study was to evaluate the
      sensitivity of crop models to systematic changes in climate for simulating
      soybean attainable yield in Southern Brazil. Four crop models were used to
      simulate yields: AQUACROP, MONICA, DSSAT, and APSIM, as well as their ensemble.
      The simulations were performed considering changes of air temperature (0, + 1.5,
      + 3.0, + 4.5, and + 6.0  degrees C), [CO2] (380, 480, 580, 680, and 780 ppm),
      rainfall (- 30, - 15, 0, + 15, and + 30%), and solar radiation (- 15, 0, + 15),
      applied to daily values. The baseline climate was from 1961 to 2014, totalizing
      53 crop seasons. The crop models simulated a reduction of attainable yield with
      temperature increase, reaching 2000 kg ha-1 for the ensemble at + 6  degrees C,
      mainly due to shorter crop cycle. For rainfall, the yield had a higher rate of
      reduction when it was diminished than when rainfall was increased. The crop
      models increased yield variability when solar radiation was changed from - 15 to
      + 15%, whereas [CO2] rise resulted in yield gains, following an asymptotic
      response, with a mean increase of 31% from 380 to 680 ppm. The models used
      require further attention to improvements in optimal and maximum cardinal
      temperature for development rate; runoff, water infiltration, deep drainage, and
      dynamic of root growth; photosynthesis parameters related to soil water
      availability; and energy balance of soil-plant system to define leaf temperature
      under elevated CO2.

PMID- 29196807
TI  - Recurrent parotid gland carcinoma: how effective is salvage surgery?
AB  - OBJECTIVE: Recurrent parotid gland carcinomas (PGCs) are poorly characterized and
      studies focusing on this topic are rare due to their low incidence. The goal of
      this study is to analyze the therapeutic strategies, prognostic factors, and
      oncological outcomes of a series of patients with recurrent PGCs. PATIENTS AND
      METHODS: Retrospective chart review (1997-2012) of patients with recurrent PGCs
      was initially treated with curative intent. RESULTS: We identified 20 patients
      with recurrent PGCs. Eleven patients presented isolated local, regional, or
      distant metastases, while the rest had recurrences in multiple sites. Recurrent
      tumors tended to present more advanced T-stage (p = 0.01) and overall stage (p <
      0.001), but not N-stage (p = 0.74) when compared to the initial tumors. Half the
      patients (50%) had distant metastases at the moment of recurrence diagnosis, and
      another three developed them after attempted salvage surgery. Only 8/20 patients
      with isolated local or regional recurrences were surgically salvaged with
      extended revision parotidectomy and neck dissection, respectively. The remaining
      12 patients were managed on palliative basis. Overall survival (31.70 months vs.
      20.73 months) and progression-free survival (28.70 months vs. 13.61 months) were
      not significantly different in patients managed surgically vs. palliatively.
      CONCLUSION: Recurrent PGCs are aggressive neoplasms with a high rate of distant
      metastases. Surgical salvage can be considered in patients with limited local
      and/or regional recurrences. The alternative to surgical salvage is palliative
      management with different chemotherapeutic regimens. Survival does not differ
      between the two strategies in the present series.

PMID- 29196808
TI  - Propagation of alpha-synuclein pathology from the olfactory bulb: possible role
      in the pathogenesis of dementia with Lewy bodies.
AB  - Olfactory limbic structures, like the amygdala, the entorhinal, and the piriform
      cortices, are closely involved in cognitive processes. Thus, besides olfactory
      dysfunctions, it is conceivable that the compromise of these structures can lead
      to cognitive impairment. The olfactory bulb is affected by alpha-synuclein
      pathology in almost all cases of both Parkinson's disease and dementia with Lewy
      bodies. The clinical distinction between these disorders relies on the timing in
      the appearance of dementia in relationship to motor symptoms. Typically, it
      occurs late in the course of Parkinson's disease, and within the first year in
      dementia with Lewy bodies. The close anatomical proximity of the olfactory bulb
      with limbic regions, together with the early occurrence of cognitive impairment
      that is observed in dementia with Lewy bodies, raise the question whether the
      propagation of alpha-synuclein pathology in this condition might originate in the
      olfactory bulb, spreading from there to other limbic structures, and thereby
      reaching the associative neocortex. This review will describe the anatomical
      basis of the olfactory system and discuss the evidence of potential spreading
      pathways from the olfactory bulb that could support the presence of early
      dementia in the setting of Lewy body disorders.

PMID- 29196809
TI  - Melatonin affects membrane integrity, intracellular reactive oxygen species,
      caspase3 activity and AKT phosphorylation in frozen thawed human sperm.
AB  - Cryopreservation is known to induce oxidative stress in spermatozoa. Although
      melatonin has powerful antioxidant properties, little is known about its effects
      on human sperm quality during cryopreservation. The present study was undertaken
      to investigate the effects of melatonin treatment on human sperm parameters
      essential for fertilization. We first evaluated the effects of various
      concentrations of melatonin (0-15 mM) on human sperm parameters such as motility,
      viability and levels of intracellular reactive oxygen species during
      cryopreservation in order to identify an optimal dose with the greatest effects
      for further studies. Liquefied semen samples were then divided into three
      aliquots: cryopreserved without melatonin (control), cryopreserved with 3 mM
      melatonin and fresh groups. After being thawed, samples were evaluated for
      motility, viability, membrane integrity, intracellular reactive oxygen species
      levels, caspase-3 activity and AKT phosphorylation. Treatment of spermatozoa with
      the various concentrations of melatonin significantly increased their motility
      and viability and decreased their intracellular reactive oxygen species levels
      compared with the control group. The optimal melatonin concentration (3 mM)
      significantly decreased the intracellular reactive oxygen species levels, caspase
      3 activity and the percentage of both dead and apoptotic-like sperm cells and
      increased the vitality, progressive motility and total motility and AKT
      phosphorylation compared with the control group. Thus, melatonin exerts
      protective effects against cryodamage during human spermatozoa cryopreservation
      and may exert its effects via the PI3K/AKT signaling pathway.

PMID- 29196810
TI  - Neural stem cells: developmental mechanisms and disease modeling.

PMID- 29196811
TI  - Cortical and subcortical connections of parietal and premotor nodes of the monkey
      hand mirror neuron network.
AB  - Mirror neurons (MNs) are a class of cells originally discovered in the monkey
      ventral premotor cortex (PMv) and inferior parietal lobule (IPL). They discharge
      during both action execution and action observation and appear to play a crucial
      role in understanding others' actions. It has been proposed that the mirror
      mechanism is based on a match between the visual description of actions, encoded
      in temporal cortical regions, and their motor representation, provided by PMv and
      IPL. However, neurons responding to action observation have been recently found
      in other cortical regions, suggesting that the mirror mechanism relies on a wider
      network. Here we provide the first description of this network by injecting
      neural tracers into physiologically identified IPL and PMv sectors containing
      hand MNs. Our results show that these sectors are reciprocally connected, in line
      with the current view, but IPL MN sectors showed virtually no direct connection
      with temporal visual areas. In addition, we found that PMv and IPL MN sectors
      share connections with several cortical regions, including the dorsal and mesial
      premotor cortex, the primary motor cortex, the secondary somatosensory cortex,
      the mid-dorsal insula and the ventrolateral prefrontal cortex, as well as
      subcortical structures, such as motor and polysensory thalamic nuclei and the mid
      dorsal claustrum. We propose that each of these regions constitutes a node of an
      "extended network", through which information relative to ongoing movements,
      social context, environmental contingencies, abstract rules, and internal states
      can influence MN activity and contribute to several socio-cognitive functions.

PMID- 29196812
TI  - Early elective delivery for fetal ventriculomegaly: are neurosurgical and medical
      complications mitigated by this practice?
AB  - PURPOSE: Antenatally diagnosed ventriculomegaly (VM) requires the balance of
      risks of neurological injury with premature delivery. The purpose of this study
      was to evaluate outcomes related to early elective delivery due to fetal VM at
      our institution. METHODS: We retrospectively assessed 120 babies (2008-2012) with
      antenatally diagnosed fetal VM. Inclusion criteria for ("early") cohort were (1)
      elective delivery occurred for expedited neurosurgical intervention between 32
      and 36 weeks EGA and (2) fetal VM noted on official antenatal ultrasound. The
      comparative "near term" cohort differed only in that delivery occurred at 37+
      weeks EGA. Statistical significance for comparative analyses set a priori at p <
      0.05. RESULTS: Babies electively delivered early had a lower birthweight (p <
      0.0001), greater ventricle width (p < 0.0001), and underwent initial CSF
      diversion sooner (p = 0.014). The early cohort (n = 22), compared to near term (n
      = 50), had a lower birthweight (p < 0.0001), greater ventricle width (p <
      0.0001), and underwent initial CSF diversion sooner (p = 0.014). The early cohort
      required more repeat procedures: (45 vs. 22% p = 0.021), and VPS removals after
      VPS infections (41 vs. 12%, p = 0.010). Additionally, newborn respiratory failure
      (32 vs. 6%, p = 0.037) was more common. Finally, of four babies who died in the
      early cohort, 2/4 died for prematurity-associated pulmonary hypoplasia.
      CONCLUSIONS: While early elective delivery for fetal VM expedites intervention
      for rapidly expanding ventricles, few benefits were identified. Our study
      concluded those infants that were delivered earlier had increased VPS infections,
      repeat neurosurgical procedures, and medical co-morbidities. A multi
      institutional prospective observational study would be needed in order to confirm
      the clinical implications of such practice.

PMID- 29196813
TI  - Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration
      and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72
      amyotrophic lateral sclerosis.
AB  - Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of
      amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic
      mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi
      directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs)
      poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or
      export defects especially caused by arginine-containing poly-GR or poly-PR have
      been proposed as significant contributors to pathogenesis based on disease
      models. We quantitatively studied and compared DPRs, nuclear pore proteins and
      C9orf72 protein in clinically related and clinically unrelated regions of the
      central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the
      hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly
      abundant in clinically related areas compared to unrelated areas (p < 0.001), and
      formed dendritic-like aggregates in the motor cortex that co-localized with pTDP
      43 (p < 0.0001). While most poly-GR dendritic inclusions were pTDP-43 positive,
      only 4% of pTDP-43 dendritic inclusions were poly-GR positive. Staining for
      arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals
      that were not specific to C9 ALS. We could not detect significant differences of
      nuclear markers RanGap, Lamin B1, and Importin beta1 in C9 ALS, although we
      observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control.
      The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons
      and glia, and nearly 50% reduced, in both clinically related frontal cortex and
      unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly
      GR DPR was unique, and localized to dendrites and pTDP43 in motor regions of C9
      ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in
      dendrites.

PMID- 29196814
TI  - Identification of candidate pathogenicity determinants of Rhizoctonia solani AG1
      IA, which causes sheath blight disease in rice.
AB  - Sheath blight disease is one of the predominant diseases of rice and it is caused
      by the necrotrophic fungal pathogen Rhizoctonia solani. The mechanistic insight
      about its widespread success as a broad host range pathogen is limited. In this
      study, we endeavor to identify pathogenicity determinants of R. solani during
      infection process in rice. Through RNAseq analysis, we identified a total of 65
      and 232 R. solani (strain BRS1) genes to be commonly upregulated in three
      different rice genotypes (PB1, Tetep, and TP309) at establishment and
      necrotrophic phase, respectively. The induction of genes encoding extracellular
      protease, ABC transporter, and transcription factors were notable during
      establishment phase. While during necrotrophic phase, several CAZymes, sugar
      transporters, cellular metabolism, and protein degradation-related genes were
      prominently induced. We have also identified few putative secreted effector
      encoding genes that were upregulated during pathogenesis. The qPCR analysis
      further validated the phase-specific expression dynamics of some selected
      putative effectors and pathogenicity-associated genes. Overall, the present study
      reports identification of key genes and processes that might be crucial for R.
      solani pathogenesis. The ability to effectively damage host cell wall and survive
      in hostile plant environment by managing oxidative stress, cytotoxic compounds,
      etc. is being proposed to be important for pathogenesis of R. solani in rice. The
      functional characterization of these genes would provide key insights about this
      important pathosystem and facilitate development of strategies to control this
      devastating disease.

PMID- 29196816
TI  - Extended nursing for the recovery of urinary functions and quality of life after
      robot-assisted laparoscopic radical prostatectomy: a randomized controlled trial.
AB  - PURPOSE: The purpose of this work is to explore the effects of continuing nursing
      care intervention on postoperative urinary control and quality of life among
      patients with prostate cancer. METHODS: This was a single-center, parallel, and
      randomized controlled trial that was carried out at the Department of Urology,
      the First Affiliated Hospital of Anhui Medical University, China. The
      participants underwent robot-assisted laparoscopic radical prostatectomy (RARP)
      between October 2014 and April 2016. The patients were randomized to the
      experimental and control groups (n=37/group). Patients in the control group
      received routine nursing care, while patients in the experimental group received
      continuing nursing care. During the 6-month follow-up, each patient was invited
      at the hospital discharge and at 1, 3, and 6 months to fill the ICI-Q-SF and SF
      36 questionnaires. RESULTS: The scores of urinary incontinence were improved in
      the intervention group compared with controls at 3 and 6 months after discharge
      (both P < 0.01). The scores of quality of life in the experimental group were
      significantly higher than control group at 1, 3, and 6 months (all P < 0.01).
      Adverse events were mild or moderate in intensity and were resolved in all
      patients. All adverse events were related to RARP. CONCLUSIONS: Continuing
      nursing care intervention had significant beneficial effects on urinary functions
      and quality of life in patients with prostate cancer after RARP. This approach
      warrants to be promoted in the clinical setting.

PMID- 29196817
TI  - Identification and characterization of a new potyvirus infecting cucurbits.
AB  - A new potyvirus, tentatively named cucurbit vein banding virus (CVBV), was
      identified in crops of cucurbits in San Pedro (Buenos Aires, Argentina). The
      complete genome sequences of two isolates of CVBV were obtained by next
      generation sequencing (Illumina). The genomic RNA consisted of 9968 and 9813
      nucleotides, respectively, and displayed typical potyvirus organization. The
      percentage identity for these two genome sequences, using BLASTn, was 77% to
      sweet potato virus c and 73% to tomato necrotic stunt virus. BLASTx analysis of
      the complete polyprotein showed that the most closely related virus is plum pox
      virus, with 48% amino acid sequence identity for both isolates. Sequence
      comparisons and phylogenetic analyses indicate that CVBV belongs to a previously
      undescribed species in genus Potyvirus.

PMID- 29196818
TI  - Detection in Japan of an equine-like G3P[8] reassortant rotavirus A strain that
      is highly homologous to European strains across all genome segments.
AB  - Equine-like G3P[8] rotavirus A strains with DS-1-like backbone genes have emerged
      since 2013. An equine-like RVA/Human-wt/JPN/15R429/2015/G3P[8] strain possessing
      I2-R2-C2-M2-A2-N2-T2-E2-H2 was detected in Japan in 2015. Its VP7 gene was >=
      99.3% identical to those of equine-like G3P[4] strains detected in Japan, and the
      remaining 10 genes were 98.6-99.8% identical to G1P[8] double-gene reassortants
      detected in Japan, Thailand and the Philippines. Thus, 15R429 was likely
      generated through reassortment between the equine-like G3P[4] and G1P[8]
      reassortant strains. Notably, 15R429 was 98.5-99.8% identical across all 11 genes
      of the equine-like G3P[8] strains detected in Spain and Hungary in 2015.

PMID- 29196815
TI  - Amyloid beta oligomers (AbetaOs) in Alzheimer's disease.
AB  - The causative role of amyloid beta 1-42 (Abeta42) aggregation in the pathogenesis
      of Alzheimer's disease (AD) has been under debate for over 25 years. Primarily,
      scientific efforts have focused on the dyshomeostasis between production and
      clearance of Abeta42. This imbalance may result from mutations either in genes
      for the substrate, i.e., amyloid precursor protein or in genes encoding
      presenilin, the enzyme of the reaction that generates Abeta42. Currently, it is
      supposed that soluble oligomers of amyloid beta (AbetaOs) and not fibrillar
      Abeta42 within neuritic plaques may be the toxic factors acting on a very early
      stage of AD, perhaps even initiating pathological cascade. For example, soluble
      AbetaOs isolated from AD patients' brains reduced number of synapses, inhibited
      long-term potentiation, and enhanced long-term synaptic depression in brain
      regions responsible for memory in animal models of AD. Concentrations of AbetaOs
      in the cerebrospinal fluid (CSF) of AD patients are often reported higher than in
      non-demented controls, and show a negative correlation with mini-mental state
      examination scores. Furthermore, increased Abeta42/oligomer ratio in the CSF of
      AD/MCI patients indicated that the presence of soluble AbetaOs in CSF may be
      linked to lowering of natively measured monomeric Abeta42 by epitopes masking,
      and hence, concentrations of AbetaOs in the CSF are postulated to as useful AD
      biomarkers.

PMID- 29196819
TI  - An effective delivery vehicle of demineralized bone matrix incorporated with
      engineered collagen-binding human bone morphogenetic protein-2 to accelerate
      spinal fusion at low dose.
AB  - The aim of this study was to investigate the feasibility and efficacy of a new
      delivery matrix using demineralized bone matrix (DBM) incorporated with collagen
      binding bone morphogenetic protein-2 (CBD-BMP-2) in the rat inter-transverse
      spinal fusion model. Sixty rats undergoing posterolateral (inter-transverse)
      spinal fusion were divided into 3 groups according to the fusion materials
      containing different components (n = 20 per group). Group A were implanted with
      DBM, Group B with combination of DBM and BMP-2 and Group C with combination of
      DBM and CBD-BMP-2. After surgery, the spinal fusion of all the rats was assessed
      by plain radiography, CT + 3D reconstruction, manual palpation and histological
      evaluation. Significant difference was found in terms of solid fusion rate among
      the three groups, with 95% in Group C, 65% in Group B and 0% in Group A (P <
      0.001). Compared with Groups B and A, new bone formation was observed earlier and
      was obvious larger, trabecular bone microarchitecture assessment was better and
      bone mineral density was statistically larger in Group C. In addition, more newly
      woven bone and osteocytes were shown by histological evaluation in Group C at 4
      weeks post-operation. The present study showed CBD domain could help BMP-2 to
      improve the efficiency of posterolateral spinal fusion. DBM scaffold activated by
      collagen-binding BMP-2 was a feasible and promising bone repair vehicle. The
      present study showed better results in terms of plain radiography, CT + 3D
      reconstruction, manual palpation and histological evaluation in the rat inter
      transverse spinal fusion model using DBM+CBD-BMP-2, compared with DBM+BMP-2 and
      DBM alone, indicating DBM scaffold activated by collagen-binding BMP-2 was a
      feasible and promising bone repair vehicle.

PMID- 29196820
TI  - Functional roles of agmatinase during the peri-implantation period of pregnancy
      in sheep.
AB  - This study investigated the effect of agmatine (Agm) in proliferation of ovine
      trophecdoderm cells (oTr1) as well as the importance of the arginine
      decarboxylase (ADC) and agmatinase (AGMAT) alternative pathway for synthesis of
      polyamines in ovine conceptuses during the peri-implantation period of pregnancy.
      Morpholino antisense oligonucleotides (MAOs) were used to inhibit translation of
      mRNAs for ODC1 alone, AGMAT alone, and their combination. Rambouillet ewes (N =
      50) were assigned randomly to the following treatments on Day 8 of pregnancy: MAO
      control (n = 10); MAO-ODC1 (n = 8); MAO-ADC (n = 6); MAO-ODC1:MAO-ADC (n = 9); or
      MAO-ODC1:MAO-AGMAT (n = 9). Ewes were ovario-hysterectomized on Day 16 of
      pregnancy to obtain uterine flushings, uterine endometrium, and conceptus
      tissues. Inhibition of translation of both ODC1 and AGMAT resulted in 22% of ewes
      having morphologically and functionally normal (elongated and healthy)
      conceptuses designated MAO-ODC1:MAO-AGMAT (A). But, 78% of the MAO-ODC1:MAO-AGMAT
      ewes had morphologically and functionally abnormal (not elongated and fragmented)
      conceptuses designated MAO-ODC1:MAO-AGMAT (B). The pregnancy rate was less (22%;
      P < 0.05) for MAO-ODC1:MAO-AGMAT ewes than for MAO-control (80%), MAO-ODC1 (75%),
      MAO-ADC (84%), and MAO-ODC1:MAO-ADC (44%) ewes. Moreover, inhibition of
      translational of both ODC1 and AGMAT mRNAs increased expression of ADC, SLC22A1,
      SLC22A2, and SLC22A3 mRNAs, as well as abundances of agmatine, putrescine,
      spermindine, and spermine in conceptus tissue. However, MAO-ODC1:AGMAT(B) ewes
      had greater abundances of agmatine, putrescine, and spermidine and reduced
      amounts of spermine in uterine flushes. Thus, in vivo knockdown of translation of
      ODC1 and AGMAT mRNAs increased expression of genes for the synthesis and
      transport of polyamines in ovine conceptuses during the peri-implantation period
      of pregnancy.

PMID- 29196821
TI  - The predictive value of MRI in the syndesmotic instability of ankle fracture.
AB  - OBJECTIVE: Although many types of ankle fracture can be combined with syndesmosis
      injury, preoperative imaging studies rarely reveal instability of the
      syndesmosis. This study assessed the use of magnetic resonance imaging (MRI) for
      syndesmotic instability in patients with unstable ankle fracture. METHODS: A
      total of 74 patients who were treated for Lauge-Hansen supination external
      rotation/Weber B type fracture or pronation external rotation/Weber C type
      fracture and who underwent MRI for preoperative assessment were enrolled. The MRI
      findings of the syndesmotic ligament and the results of an intraoperative stress
      test were evaluated. RESULTS: Twenty-six patients had a positive result on the
      intraoperative stress test for syndesmotic instability. The MRI findings of the
      syndesmotic ligaments revealed that complete tear of the posterior inferior
      tibiofibular ligament (PITFL) was the most reliable predictor of syndesmotic
      instability (sensitivity, 74%; specificity, 78%; positive predictive value, 54%).
      Interobserver agreement for the intraoperative stress test and MRI assessment was
      excellent, except for the MRI findings of the interosseous ligament (62%
      agreement; kappa, 0.3). CONCLUSIONS: Complete tear of the PITFL on MRI has
      additional diagnostic value for syndesmotic instability in ankle fracture.
      However, because the sensitivity might not be sufficient to justify the costs
      associated with MRI, cost-effectiveness should be considered.

PMID- 29196822
TI  - Osteogenic melanoma: report of a case mimicking osteosarcoma and review of the
      literature.
AB  - A 32-year-old male presented with a right thumb lesion of 11-month duration. A
      clinical diagnosis of pyogenic granuloma was entertained but the lesion failed to
      respond to conservative therapy and eventually necessitated amputation of his
      thumb. MRI of the right thumb showed an ill-defined, heterogeneously enhancing,
      infiltrating mass within the dorsal soft tissues abutting the distal phalanx and
      measuring 4.2 * 2.4 * 0.7 cm. Histologically, the tumor was composed of a high
      grade osteosarcoma with a chondrosarcomatous component localized within the
      underlying bone and a more superficial spindle cell component in the overlying
      soft tissue. The epidermis was focally ulcerated overlying the lesion. The key to
      the diagnosis was provided by intense staining of the spindle cell component for
      S100 protein indicative of a spindle cell melanoma. The presence of an associated
      osteogenic sarcomatous component established a final diagnosis of osteogenic
      melanoma. The localization of this element to phalangeal bone is distinctly
      unusual and resulted in the close resemblance to a primary osteogenic sarcoma.

PMID- 29196824
TI  - Spirochetal Lipoproteins in Pathogenesis and Immunity.
AB  - Lipoproteins are lipid-modified proteins that dominate the spirochetal proteome.
      While found in all bacteria, spirochetal lipoproteins have unique features and
      play critical roles in spirochete biology. For this reason, considerable effort
      has been devoted to determining how the lipoproteome is generated. Essential
      features of the structural elements of lipoproteins are now understood with
      greater clarity, enabling greater confidence in identification of lipoproteins
      from genomic sequences. The journey from the ribosome to the outer membrane, and
      in some cases, to the cellular surface has been defined, including secretion,
      lipidation, sorting, and export across the outer membrane. Given their abundance
      and importance, it is not surprising that spirochetes have developed a number of
      strategies for regulating the spatiotemporal expression of lipoproteins. In some
      cases, lipoprotein expression is tied to various environmental cues, while in
      other cases, it is linked to growth rate. This regulation enables spirochetes to
      express certain lipoproteins at high levels in one phase of the spirochete
      lifecycle, while dramatically downregulating the same lipoproteins in other
      phases. The mammalian host has developed specialized mechanisms for recognizing
      lipoproteins and triggering an immune response. Evasion of that immune response
      is essential for spirochete persistence. For this reason, spirochetes have
      developed mechanisms for altering lipoproteins. Lipoproteins recognized by
      antibodies formed during infection are key serodiagnostic antigens. In addition,
      lipoprotein vaccines have been developed for generating an immune response to
      control or prevent a spirochete infection. This chapter summarizes our current
      understanding of lipoproteins in interactions of spirochetes with their hosts.

PMID- 29196823
TI  - Quantitative mapping of glenohumeral cartilage in asymptomatic subjects using 3 T
      magnetic resonance imaging.
AB  - OBJECTIVE: The purpose of this study was to develop quantitative T2 mapping
      methodology in asymptomatic shoulders for the entire mappable region of the
      glenohumeral cartilage in the coronal and sagittal planes, to assess the
      feasibility and limitations of the development of a diagnostic tool for future
      application in symptomatic patients. MATERIALS AND METHODS: Twenty-one
      asymptomatic volunteers underwent sagittal and coronal glenohumeral T2 mapping,
      as the spherical geometry of the humeral head obviates the need to evaluate the
      entire glenohumeral cartilage in a single plane. The humeral head cartilage
      orthogonal to the mapping plane was manually segmented in the sagittal and
      coronal planes, whereas the glenoid cartilage was segmented in the coronal plane.
      Cartilage T2 summary statistics were calculated and coverage in each mapping
      plane was qualitatively assessed. RESULTS: The mean +/- standard deviation of the
      glenoid cartilage T2 was 38 +/- 2 ms. The coronal and sagittal mapping planes
      captured different regions of the humeral head with some overlap: inferior-medial
      to superior-lateral versus superior/superior-lateral to anterior-lateral and
      posterior-lateral respectively. The mean humeral head cartilage T2 in the coronal
      plane was 41 +/- 3 ms, which was significantly different (p < 0.05) from the
      sagittal plane mean of 34 +/- 2 ms. CONCLUSION: This study measured
      characteristic glenoid and humeral head cartilage T2 values over the area
      mappable with two planes. Importantly, this study demonstrated that two
      dimensional mapping in a single plane or two combined planes cannot capture the
      entirety of the semi-spherical humeral head cartilage. This highlights the need
      for three-dimensional T2 mapping techniques in the shoulder.

PMID- 29196826
TI  - Botulinum toxin: a novel therapy for clozapine-induced sialorrhoea.

PMID- 29196825
TI  - Changes in prescription patterns in older hospitalized patients: the impact of
      FORTA on disease-related over- and under-treatments.
AB  - PURPOSE: Physicians often face difficulties in choosing appropriate medications
      for multimorbid older people. The FORTA (Fit for the Aged) classification (A:
      absolutely, B: beneficial, C: careful, D: don't) was proposed as a clinical tool
      for improving the quality of drug treatment in the aged. As an implicit tool,
      FORTA has been shown to aid medication optimization and improve clinical end
      points in the VALFORTA trial. In this prospective randomized controlled study,
      207 older hospitalized patients received standard geriatric treatment and 202
      patients received FORTA-guided treatment. METHODS: Here, changes of drug
      prescriptions at the anatomical-therapeutic-chemical system (ATC) level were
      evaluated separately for important diagnoses in descriptive analyses; over- and
      under-treatment rates were compared between groups. RESULTS: At the individual
      drug/drug class level related to all important diagnoses, the application of
      FORTA significantly improved under-treatments for 12 drugs/drug classes (e.g.,
      ACE inhibitors to treat arterial hypertension) and over-treatments for 7
      drugs/drug classes (e.g., proton pump inhibitors to treat gastroesophageal reflux
      disease). CONCLUSIONS: FORTA representing the first combined positive/negative
      labeling approach at the individual drug level aids the optimization of drug
      treatment in older people as detected for drugs/drug classes at the ATC level in
      important indications. FORTA is effective in addressing over- and under
      treatments even if analyzed for smaller subgroups of VALFORTA.

PMID- 29196827
TI  - Bone marrow aspirations in oncological patients: experience from an in-house
      standard in paediatrics.
AB  - BACKGROUND: Nearly all paediatric patients require deep sedation when undergoing
      bone marrow aspiration (BMA). We analyzed the data from our protocols documented
      in a standardised procedure for bone marrow puncture over a period of 2 years.
      METHODS: Our standard included the documentation of personal data as well as
      vital parameters. In addition, we documented all medications administered,
      potential complications and required intervention measures, as necessary.
      RESULTS: A total of 107 protocols were available for the evaluation. Our standard
      covered the usage of midazolam and S-ketamine and resulted in complications in
      just 9 patients, which could be remedied using simple measures. For both active
      substances, the dosage necessary to reach sufficient deep analgosedation was
      significantly higher for patients under 24 months of age. CONCLUSIONS: Our
      standard for BMA provides a practical and feasible procedure. In addition to good
      examination conditions, our standard also helps ensure the safety of our
      patients.

PMID- 29196828
TI  - Space Use and Social Mating System of the Hantavirus Host, Oligoryzomys
      longicaudatus.
AB  - The long-tailed mouse, Oligoryzomys longicaudatus (Cricetidae: Sigmodontinae), is
      the major host of Andes hantavirus, the etiological agent of hantavirus pulmonary
      syndrome in the south of Argentina and Chile. Studying the ecology of this
      species is necessary to understand how Andes hantavirus is maintained in nature.
      In this study, we examine the home range size and intra- and intersexual overlap
      degree of male and female O. longicaudatus in order to elucidate the mating
      system of this species. To our knowledge, this research provides the first
      documentation, obtained from a specific design, of spacing and mating systems in
      this species in Argentina. The study was conducted seasonally from April (autumn)
      2012 to October (spring) 2013 in a shrubland habitat of Cholila, Andean region,
      Argentina. We studied spacing patterns using 59 and 51 home ranges established by
      adult males and females, respectively, in two 3.24 ha capture-marked and
      recapture grids. Significant differences between sexes in home range size and
      overlap degree were found. Male home ranges were always larger than those of
      females. We observed exclusive space use both among males and females (13.15 +/-
      18.67, and 3.60 +/- 3.43%, respectively). Considering only those males that get
      access to receptive females (40%), average intersexual overlap value was about
      30.82 +/- 19.73%. Sexual differences in home range sizes and the spatial
      avoidance between breeding males, that would reflect intrasexual competition for
      receptive females, allows us to propose a polygynous mating system for O.
      longicaudatus.

PMID- 29196829
TI  - Investigation of fullerenol-induced changes in poroelasticity of human
      hepatocellular carcinoma by AFM-based creep tests.
AB  - In this study, atomic force microscopy (AFM) is used to investigate the
      alterations of the poroelastic properties of hepatocellular carcinoma (SMMC-7721)
      cells treated with fullerenol. The SMMC-7721 cells were subject to AFM-based
      creep tests, and a corresponding poroelastic indentation model was used to
      determine the poroelastic parameters by curve fitting. Comparative analyses
      indicated that the both permeability and diffusion of fullerenol-treated cells
      increased significantly while their elastic modulus decreased by a small amount.
      From the change in the trend of the determined parameter, we verified the
      corresponding alternations of cytoskeleton (mainly filaments actin), which was
      reported by the previous study using confocal imaging method. Our investigation
      on SMMC-7721 cell reveals that the poroelastic properties could provide a better
      understanding how the cancer cells are affected by fullerenol or potentially
      other drugs which could find possible applications in drug efficacy test, cancer
      diagnosis and secure therapies.

PMID- 29196830
TI  - A Multi-site In-depth Evaluation of the Quanterix Simoa from a User's
      Perspective.
AB  - An in-depth evaluation of the Quanterix(c) SimoaTM platform was undertaken by
      scientists from the AAPS Emerging Technologies Focus Group to determine the
      overall performance of the technology as well as provide guidance to future
      users. In order to test the platform in a non-GLP bioanalytical setting, a cross
      site evaluation of the Quanterix IL-6 biomarker kit was performed. Parameters
      tested during this evaluation included sensitivity, accuracy and precision, and
      parallelism in human serum from normal individuals. The results demonstrated
      improved sensitivity compared to the claimed sensitivity of other commercially
      available IL-6 kits and showed excellent site-to-site reproducibility. Observed
      issues included difficulties with system reliability and a lack of parallelism
      and specificity in a subset of samples. Overall, these results demonstrate that
      while there are challenges to the Simoa platform this technology offers
      automation capabilities and excellent sensitivity that enhance bioanalysis
      especially of low-abundance analytes.

PMID- 29196832
TI  - Comment on "Effects of the GaAlAs diode laser (780 nm) on the periodontal tissues
      during orthodontic tooth movement in diabetes rats: histomorphological and
      immunohistochemical analysis".

PMID- 29196831
TI  - Laser for bone healing after oral surgery: systematic review.
AB  - The purpose of this study is to perform a systematic review on the use of lasers
      in oral surgery for bone healing. Selection of articles was carried out by two
      evaluators in Pubmed and Web of Science databases for published articles and
      OpenGray for gray literature. Search strategy was developed based on the PICO
      Question "Does the use of lasers after oral surgery improve bone healing?".
      Eligibility criteria were: being on laser; evaluate bone healing; involve oral
      surgery; do not be about implant, periodontics, orthodontics, osteonecrosis or
      radiotherapy, nor revisions, clinical cases, etc. Data were collected from each
      article in a structured spreadsheet and a descriptive analysis was performed.
      Risk assessment of bias of the articles was carried out through the tool
      elaborated by the Cochrane collaboration. A total of 827 potentially relevant
      references were identified. No articles were found in OpenGray. Eleven articles
      met the eligibility criteria and were included in the systematic review. Most of
      studies were in vivo and in jaw, being conducted with low-power lasers which were
      applied immediately after the surgical procedure of extraction. Neoformation and
      bone density were the outcomes of choice and there was a tendency of increase in
      bone density, neoformation, regeneration, mineralization, or bone condensation
      when laser was applied. Regarding the bias risk assessment, studies were not
      clear in reporting most of the parameters. Low-power laser therapy seems to
      reduce time of bone healing in oral surgery, although there are no defined
      protocols and the level of evidence is still considered weak.

PMID- 29196833
TI  - Chondroitin sulfate and glucosamine sulfate associated to photobiomodulation
      prevents degenerative morphological changes in an experimental model of
      osteoarthritis in rats.
AB  - The aim of this study was to compare the effects of combined treatment with
      chondroitin sulfate and glucosamine sulfate (CS/Gl) and photobiomodulation (PBM)
      on the degenerative process related to osteoarthritis (OA) in the articular
      cartilage in rats. Forty male Wistar rats were randomly divided into four groups:
      OA control group (CG); OA animals submitted to PBM treatment (PBM); OA animals
      submitted to CS/Gl treatment (CS/Gl); OA submitted to CS/GS associated with PBM
      treatments (GS/Gl + PBM). The CS/Gl started 48 h after the surgery, and they were
      performed for 29 consecutive days. Moreover, PBM was performed after the CS/Gl
      administration on the left joint. Morphological characteristics and
      immunoexpression of interleukin 10 (IL-10) and 1 beta (IL-1beta) and collagen
      type II (Col II) of the articular cartilage were evaluated. The results showed
      that all treated groups (CS/Gl and PBM) presented attenuation signs of
      degenerative process (measured by histopathological analysis) and lower density
      chondrocytes [PBM (p = 0.0017); CS/Gl (p = 0.0153) and CS/Gl + PBM (p = 0.002)].
      Additionally, CS/Gl [associated (p = 0.0089) or not with PBM (p = 0.0059)] showed
      significative lower values for OARSI grade evaluation. Furthermore, CS/GS + PBM
      decreased IL-1beta protein expression (p = 0.0359) and increased IL-10 (p =
      0.028) and Col II imunoexpression (p = 0.0204) compared to CG. This study showed
      that CS/Gl associated with PBM was effective in modulating inflammatory process
      and preventing the articular tissue degradation in the knees OA rats.

PMID- 29196835
TI  - Eye contact effects on social preference and face recognition in normal ageing
      and in Alzheimer's disease.
AB  - Perceiving a direct gaze (i.e. another individual's gaze directed to the observer
      leading to eye contact) influences positively a wide range of cognitive
      processes. In particular, direct gaze perception is known to stimulate memory for
      other's faces and to increase their likeability. Alzheimer's disease (AD) results
      in social withdrawal and cognitive decline. However, patients show preserved eye
      contact behaviours until the middle stage of the disease. The eye contact effects
      could be preserved in AD and be used to compensate for cognitive and social
      deficits. Yet, it is unknown whether these effects are preserved in normal
      ageing. The aim of this study was to address whether the positive effects of eye
      contact on memory for faces and likeability of others are preserved in healthy
      older adults and in patients with early to mild AD. Nineteen AD patients, 20
      older adults and 20 young adults participated in our study. Participants were
      first presented with faces displaying either direct or averted gaze and rated
      each face's degree of likeability. They were then asked to identify the faces
      they had previously seen during a surprise recognition test. Results showed that
      the effect of eye contact on other's likeability was preserved in normal ageing
      and in AD. By contrast, an effect of eye contact on memory for faces seems to
      emerge only in young participants, suggesting that this effect declines with
      ageing. Interestingly, however, AD patients show a positive correlation between
      ratings of likeability and recognition scores, suggesting that they implicitly
      allocated their encoding resources to most likeable faces. These results open a
      new way for a "compensating" therapy in AD.

PMID- 29196834
TI  - Motor-cognitive dual-task performance: effects of a concurrent motor task on
      distinct components of visual processing capacity.
AB  - Dual tasking, or the simultaneous execution of two continuous tasks, is
      frequently associated with a performance decline that can be explained within a
      capacity sharing framework. In this study, we assessed the effects of a
      concurrent motor task on the efficiency of visual information uptake based on the
      'theory of visual attention' (TVA). TVA provides parameter estimates reflecting
      distinct components of visual processing capacity: perceptual threshold, visual
      processing speed, and visual short-term memory (VSTM) storage capacity. Moreover,
      goodness-of-fit values and bootstrapping estimates were derived to test whether
      the TVA-model is validly applicable also under dual task conditions, and whether
      the robustness of parameter estimates is comparable in single- and dual-task
      conditions. 24 subjects of middle to higher age performed a continuous tapping
      task, and a visual processing task (whole report of briefly presented letter
      arrays) under both single- and dual-task conditions. Results suggest a decline of
      both visual processing capacity and VSTM storage capacity under dual-task
      conditions, while the perceptual threshold remained unaffected by a concurrent
      motor task. In addition, goodness-of-fit values and bootstrapping estimates
      support the notion that participants processed the visual task in a qualitatively
      comparable, although quantitatively less efficient way under dual-task
      conditions. The results support a capacity sharing account of motor-cognitive
      dual tasking and suggest that even performing a relatively simple motor task
      relies on central attentional capacity that is necessary for efficient visual
      information uptake.

PMID- 29196836
TI  - Modifiable and non-modifiable risk factors for preterm delivery among adolescent
      and young adult cancer survivors.
AB  - PURPOSE: A cancer diagnosis in adolescence and young adulthood (AYA, ages 15-39)
      may affect future pregnancy outcomes. Previous studies have reported an increased
      risk of preterm delivery (< 37 weeks of gestation) after maternal cancer
      treatment. In this analysis, we evaluated whether non-cancer characteristics
      modify the association between an AYA cancer history and preterm birth. METHODS:
      North Carolina Central Cancer Registry records (2000-2013) were linked to state
      birth certificate files (2000-2014) to identify births to AYA cancer survivors (n
      = 1,980). A comparison cohort of births to women without a cancer diagnosis was
      selected from birth certificate files (n = 11,860). Log-binomial regression was
      used to estimate risk ratios (RR) and 95% confidence intervals (CI) for preterm
      delivery. Effect modification by early prenatal care (1st trimester; yes/no),
      race/ethnicity (white/black/other), previous live births (0/1+), maternal age (<
      25/25-29/30-34/35+), smoking during pregnancy (any/none), and education (high
      school or less/some college/Bachelor's degree or higher) was evaluated using
      likelihood ratio tests (LRT). RESULTS: Overall, preterm births were more common
      among AYA survivors than the comparison group (RR = 1.24, CI 1.07-1.43). The
      association was stronger among those who did not receive early prenatal care (RR
      = 1.73, CI 1.26-2.37) than among those who did (RR = 1.15, CI 0.98-1.35; LRT p =
      0.03). Maternal age < 25 was also associated with a greater increase in preterm
      birth (< 25: RR = 1.80, CI 1.27-2.54; LRT p = 0.07). Associations did not vary
      strongly by other factors evaluated. CONCLUSIONS: An AYA cancer diagnosis may be
      associated with an increased risk of preterm birth, particularly among women who
      are younger and receive late or no prenatal care.

PMID- 29196837
TI  - Protective effect of aspirin treatment on mouse behavior in the acute phase of
      experimental infection with Trypanosoma cruzi.
AB  - Chagas disease is a potentially fatal disease caused by the parasite Trypanosoma
      cruzi, which can in some cases affect the central nervous system. The objective
      was to evaluate the effect of aspirin (ASA) in the behavior of mice infected with
      T. cruzi during the acute phase. This was an experimental study with random
      assignation. Twenty four BALB/c mice were divided into four groups of six animals
      each as follows: only ASA (OA), ASA before infection (BI), ASA after infection
      (AI) and only infection (OI). The strain used for infection was M/HOM/Bra/53/Y.
      An ASA dose of 100 mg/kg per day was administered 72 h before infection to BI
      group and the same dose 48 h after infection to AI group. Mice behavior in the
      open field test, mortality, and brain histopathology was evaluated. Data were
      analyzed using ANOVA, chi square test, and Kaplan-Meier with long-rank for
      survival analysis. In the open field test, the OA group has similar results with
      the BI group, in the variables of immobility and escape. Also, the OA group
      displayed significantly higher rates of micturition (p < 0.001) and defecation (p
      < 0.001) compared to infected groups. Mortality was higher in BI group (p =
      0.02). The presence of T. cruzi amastigotes were higher in brain tissues of the
      AI and OI groups (p = 0.008). In conclusion, the administration of ASA before
      infection seemed to prevent behavioral changes induced by the acute infection,
      but it led to accelerated mortality. The study highlighted the potential
      importance of the pathways inhibited by ASA in the early hours of acute infection
      with T. cruzi.

PMID- 29196838
TI  - Inverse correlation between left ventricular end-diastolic pressure and contrast
      induced nephropathy in patients undergoing percutaneous coronary intervention.
AB  - BACKGROUND: There is a rising incidence of contrast-induced nephropathy (CIN),
      which is defined as either a 25% relative increase or an absolute increase of 0.5
      mg/dL (44.2 umol/L) in the serum creatinine (Scr) level at 48-72 h after
      administration of iodinated contrast media (CM). We investigated the relationship
      between left ventricular end-diastolic pressure (LVEDP) and CIN in patients
      undergoing percutaneous coronary intervention (PCI). METHODS: A total of 431
      consecutive patients with coronary artery disease undergoing PCI were divided
      into four groups based on LVEDP quartile cut-off points. Enrolled patients were
      given continuous intravenous infusion of normal saline starting 4 h before PCI
      and lasting 24 h. At the end of hydration administration, 20 mg furosemide was
      slowly injected intravenously. Serum creatinine (Scr), creatinine clearance rate
      (Ccr), and glomerular filtration rate (GFR) were detected before and after PCI.
      RESULTS: There were significant differences in the incidences of CIN in the four
      groups: 10.25% in the Q1 group, 5.55% in the Q2 group, 5.31% in the Q3 group, and
      1.06% in the Q4 group (P < 0.05). With increasing LVEDP, the incidence of CIN
      decreased significantly (OR 0.581, 95% CI 0.367-0.920). Received operating
      characteristic curve analysis of the predictive value of LVEDP for CIN produced
      area under the curve values was 0.641, with a sensitivity of 74.1% and
      specificity of 48%. The optimal LVEDP cut-off for the occurrence of CIN was 14.5
      mmHg. CONCLUSIONS: LVEDP correlated inversely with CIN in patients undergoing
      PCI.

PMID- 29196839
TI  - Purification and activity characterization of polysaccharides in the medicinal
      lichen Umbilicaria tornata from Taibai Mountain, China.
AB  - Water-soluble polysaccharides from Umbilicaria tornata (UTP) were purified and
      preliminarily characterized. The antioxidant and antitumor activities of crude
      UTP and two purified fractions (UTP-1 and UTP-2) were evaluated using in vitro
      experiments. The results showed that the molecular weights of UTP-1 and UTP-2
      were 84.86 and 28.66 kDa, respectively. Both UTP-1 and UTP-2 were composed of
      glucose and xylose, with their molar ratios being 1.3:0.9 and 0.9:4.6,
      respectively. In addition, crude UTP, UTP-1 and UTP-2 showed dose-dependent DPPH
      and hydroxyl radical scavenging and reducing activities. However, crude UTP
      exhibited stronger antioxidant activity than UTP-1 and UTP-2, particularly in
      terms of DPPH radicals. Crude UTP and the two purified fractions inhibited the
      growth of HeLa, HepG2, A375, MCF-7, SGC7901 and Caco2 cancer cells in vitro.
      Compared with UTP-1 and UTP-2, crude UTP presented significantly higher antitumor
      activity in vitro against HeLa and HepG2 cells (p < 0.05). These findings provide
      a scientific basis for the deeper exploration and resource development of U.
      tornata.

PMID- 29196840
TI  - Conception of the Lubeck Toolbox curriculum for basic minimally invasive surgery
      skills.
AB  - PURPOSE: Difficulties at the beginning of the learning curve in minimally
      invasive surgery (MIS) can well be overcome by simulation outside the operating
      room. Despite a great number of available devices, standardized, structured, and
      validated training curricula for video simulators are scarce. METHODS: The Lubeck
      Toolbox (LTB) video trainer provides six training modules and online video
      tutorials. Proficiency levels for the tasks were defined by performance analysis
      of MIS experts (n = 15). Mean values of the best performed repetitions were set
      as benchmarks for a validation study with n = 30 MIS novices and the learning
      curves calculated. The novices performed a cholecystectomy on a pig organ model
      before and after the curriculum which were analyzed using the GOALS score.
      RESULTS: Benchmarks defined by expert performance for the task Nos. 1 to 6 were
      72 s (+/- 8) (Pack Your Luggage), 49 s (+/- 9) (Weaving), 66 s (+/- 10) (Chinese
      Jump Rope), 89 s (+/- 28) (Triangle Cut), 138 s (+/- 44) (Hammer Cut), and 98 (+/
      22) (Suturing). The median numbers of required repetitions by the novices to
      reach the proficiency level were n = 42 (7-80), n = 26 (9-55), n = 32 (14-77), n
      = 44 (15-59), n = 19 (6-68), and n = 26 (15-60). These values were all located at
      the beginning of the plateau phase of the learning curves. GOALS score improved
      significantly after completion of the curriculum (18.0 (+/- 2.6) vs. 10.9 (+/-
      1.6), p < 0.0001). CONCLUSION: The LTB curriculum constitutes a new highly
      standardized and proficiency level-based training program for basic skills in
      MIS. Transferability of the task content to a (sub)-realistic environment could
      be demonstrated. Still, future trials will have to further validate the
      effectiveness of the LTB curriculum.

PMID- 29196841
TI  - Implication of visceral obesity in patients with esophageal squamous cell
      carcinoma.
AB  - PURPOSE: Visceral obesity is considered to be associated not only with chronic
      systemic inflammation but also with aggressive cancer behavior. However, the
      implication of visceral obesity in patients with esophageal squamous cell
      carcinoma (ESCC) is unclear. METHODS: Computed tomography volumetry was performed
      in 364 patients who underwent esophagectomy for ESCC. We calculated the ratio of
      the visceral fat area to the subcutaneous fat area (VS ratio), which is a
      valuable parameter of visceral obesity. Then, the clinicopathological
      characteristics were compared between patients with low VS ratio and those with
      high VS ratio. RESULTS: Overall and disease-specific survivals of patients with
      high VS ratio were significantly worse than those with low VS ratio (P < 0.001 in
      both). Patients with high VS ratio had considerably more advanced pN factor,
      higher prevalence of lymphatic invasion, and more number of metastatic lymph
      nodes than those with low VS ratio (P = 0.044, < 0.001, and 0.006, respectively).
      Among patients who received preoperative treatment, high VS ratio correlated with
      poor response to preoperative treatment (P = 0.040). CONCLUSIONS: Visceral
      obesity was associated with lymphatic invasiveness and poor response to
      preoperative treatment in patients with ESCC, which may negatively influence
      their prognosis.

PMID- 29196842
TI  - Involvement in care in pediatric cancer patients: implications for treatment
      compliance, mental health and health-related quality of life.
AB  - PURPOSE: The present study developed a new measure of involvement in care of
      pediatric oncology patients termed the Child Involvement in Care Scale (CICS),
      and empirically examined the mental health consequences of involvement in care
      for children with cancer. METHOD: The CICS was administered to 236 children with
      cancer aged 8-12 who were recruited from three large hospitals in Israel. The
      children also completed questionnaires on their mental-health symptoms and
      emotional well-being. The children's parents completed measures on their child's
      compliance with treatment and health-related quality of life (HRQOL). RESULTS:
      Exploratory and confirmatory factor analyses supported a 2-factor structure
      (knowledge and participation), representing different aspects of involvement in
      care. Compliance with treatment served as a mediator for the relationships
      between involvement in care and health-related outcomes. Involvement in care was
      positively associated with higher treatment compliance. In addition, treatment
      compliance was positively associated with HRQOL and positive emotions but
      negatively associated with psychiatric symptoms. CONCLUSION: Pediatric cancer
      patients' involvement in the process of care is linked to better treatment
      compliance and mental health outcomes. Additional research is needed to examine
      the specific conditions and contexts in which involvement in care contributes to
      mental health and subjective well-being of children with cancer.

PMID- 29196844
TI  - Correction to: The Microbiome of Eucalyptus Roots under Different Management
      Conditions and Its Potential for Biological Nitrogen Fixation.
AB  - The original version of this article unfortunately contained mistakes in the
      first author's name and the running page headers.

PMID- 29196843
TI  - Huanglongbing Control: Perhaps the End of the Beginning.
AB  - Huanglongbing (HLB) is one of the most destructive citrus plant diseases
      worldwide. It is associated with the fastidious phloem-limited alpha
      proteobacteria 'Candidatus Liberibacter asiaticus', 'Ca. Liberibacter africanus'
      and 'Ca. Liberibacter americanus'. In recent years, HLB-associated Liberibacters
      have extended to North and South America. The causal agents of HLB have been
      putatively identified, and their transmission pathways and worldwide population
      structure have been extensively studied. However, very little is known about the
      epidemiologic relationships of Ca. L. asiaticus, which has limited the scope of
      HLB research and especially the development of control strategies. HLB-affected
      plants produce damaged fruits and die within several years. To control the
      disease, scientists have developed new compounds and screened existing compounds
      for their antibiotic and antimicrobial activities against the disease. These
      compounds, however, have very little or even no effect on the disease. The aim of
      the present review was to compile and compare different methods of HLB disease
      control with newly developed integrative strategies. In light of recent studies,
      we also describe how to control the vectors of this disease and the biological
      control of other citrus plant pathogens. This work could steer the attention of
      scientists towards integrative control strategies.

PMID- 29196845
TI  - Pole lengths influence O2-cost during double poling in highly trained cross
      country skiers.
AB  - PURPOSE: In elite cross-country skiing, double poling is used in different
      terrain. This study compared O2-cost and kinematics during double poling with
      four different pole lengths [self-selected (SS), SS - 5 cm, SS + 5 cm, SS + 10
      cm] at Low versus Moderate incline. METHODS: Thirteen highly trained male cross
      country skiers (mean +/- SD 23 +/- 3 years; 182 +/- 4 cm; 77 +/- 6 kg) completed
      eight submaximal trials with roller skis on a treadmill at two conditions: "Low
      incline" (1.7 degrees ; 4.5 m s-1) and "Moderate incline" (4.5 degrees ; 2.5 m s
      1) with each of the four pole lengths. O2-cost and 3D body kinematics were
      assessed in each trial. RESULTS: In Low incline, SS + 10 cm induced a lower O2
      cost than all the other pole lengths [P < 0.05; effect size (ES) 0.5-0.8],
      whereas no differences were found between the remaining pole lengths (P > 0.05;
      ES 0.2-0.4). In Moderate incline, significant differences between all pole
      lengths were found for O2-cost, with SS - 5 cm > SS > SS + 5 cm > SS + 10 cm (P <
      0.05; ES 0.6-1.8). The relative differences in O2-cost between SS and the other
      pole lengths were greater in Moderate incline than Low incline (SS - 5 cm; 1.5%,
      ES 0.8, SS + 5 cm; 1.3%, ES 1.0, and SS + 10 cm; 1.9%, ES 1.0, all P < 0.05). No
      difference was found in cycle, poling or reposition times between pole lengths.
      However, at both conditions a smaller total vertical displacement of center of
      mass was observed with SS + 10 cm compared to the other pole lengths. CONCLUSION:
      Increasing pole length from SS - 5 cm to SS + 10 cm during double poling induced
      lower O2-cost and this advantage was greater in Moderate compared to Low incline.

PMID- 29196846
TI  - The availability of water associated with glycogen during dehydration: a
      reservoir or raindrop?
AB  - PURPOSE: This study evaluated whether glycogen-associated water is a protected
      entity not subject to normal osmotic homeostasis. An investigation into practical
      and theoretical aspects of the functionality of this water as a determinant of
      osmolality, dehydration, and glycogen concentration was undertaken. METHODS: In
      vitro experiments were conducted to determine the intrinsic osmolality of
      glycogen-potassium phosphate mixtures as would be found intra-cellularly at
      glycogen concentrations of 2% for muscle and 5 and 10% for liver. Protected water
      would not be available to ionic and osmotic considerations, whereas free water
      would obey normal osmotic constraints. In addition, the impact of 2 L of sweat
      loss in situations of muscle glycogen repletion and depletion was computed to
      establish whether water associated with glycogen is of practical benefit (e.g.,
      to increase "available total body water"). RESULTS: The osmolality of glycogen
      potassium phosphate mixtures is predictable at 2% glycogen concentration
      (predicted 267, measured 265.0 +/- 4.7 mOsmol kg-1) indicating that glycogen
      associated water is completely available to all ions and is likely part of the
      greater osmotic system of the body. At higher glycogen concentrations (5 and
      10%), there was a small amount of glycogen water (~ 10-20%) that could be
      considered protected. However, the majority of the glycogen-associated water
      behaved to normal osmotic considerations. The theoretical exercise of selective
      dehydration (2 L) indicated a marginal advantage to components of total body
      water such as plasma volume (1.57% or 55 mL) when starting exercise glycogen
      replete. CONCLUSION: Glycogen-associated water does not appear to be a separate
      reservoir and is not able to uniquely replete water loss during dehydration.

PMID- 29196847
TI  - Body position influences arterial occlusion pressure: implications for the
      standardization of pressure during blood flow restricted exercise.
AB  - PURPOSE: Arterial occlusion pressure (AOP) measured in a supine position is often
      used to set cuff pressures for blood flow restricted exercise (BFRE). However,
      supine AOP may not reflect seated or standing AOP, thus potentially influencing
      the degree of occlusion. The primary aim of the study was to investigate the
      effect of body position on AOP. A secondary aim was to investigate predictors of
      AOP using wide and narrow cuffs. METHODS: Twenty-four subjects underwent
      measurements of thigh circumference, skinfold and blood pressure, followed by
      assessments of thigh AOP in supine and seated positions with a wide and a narrow
      cuff, respectively, using Doppler ultrasound. RESULTS: In the supine position,
      AOP was 148 +/- 19 and 348 +/- 94 mmHg with the wide and narrow cuff,
      respectively. This increased to 177 +/- 20 and 409 +/- 101 mmHg in the seated
      position, with correlations between supine and seated AOP of R 2 = 0.81 and R 2 =
      0.50 for the wide and narrow cuff, respectively. For both cuff widths, thigh
      circumference constituted the strongest predictor of AOP, with diastolic blood
      pressure explaining additional variance with the wide cuff. The predictive
      strength of these variables did not differ between body positions. CONCLUSION:
      Our results indicate that body position strongly influences lower limb AOP,
      especially with narrow cuffs, yielding very high AOP (>= 500-600 mmHg) in some
      subjects. This should be taken into account in the standardization of cuff
      pressures used during BFRE to better control the physiological effects of BFRE.

PMID- 29196848
TI  - Left-sided congenital heart lesions in mosaic Turner syndrome.
AB  - In the era of the diseasomes and interactome networks, linking genetics with
      phenotypic traits in Turner syndrome should be studied thoroughly. As a part of
      this stratagem, mosaicism of both X and Y chromosome which is a common finding in
      TS and an evaluation of congenital heart diseases in the different situations of
      mosaic TS types, can be helpful in the identification of disturbed sex
      chromosomes, genes and signaling pathway actors. Here we report the case of a
      mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms
      and dissections at an early age. The mosaicism included two cell lines, well
      defined at the cytogenetic and molecular levels: a cell line which is monosomic
      for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal
      genes that are present on the X and Y chromosomes and escape X inactivation:
      45,X[8]/46,X,idic(Y)(pter->q11.2::q11.2->pter)[42]. This case generates two
      hypotheses about the contribution of genes linked to the sex chromosomes and the
      signaling pathways involving these genes, in left-sided heart diseases. The first
      hypothesis suggests the interaction between X chromosome and autosomal genes or
      loci of aortic development, possibly dose-dependent, and which could be in the
      framework of TGF-beta-SMAD signaling pathways. The second implies that left-sided
      congenital heart lesions involve sex chromosomes loci. The reduced dosage of X
      chromosome gene(s), escaping X inactivation during development, contributes to
      this type of CHD. Regarding our case, these X chromosome genes may have
      homologues at the Y chromosome, but the process of inactivation of the
      centromeres of the isodicentric Y spreads to the concerned Y chromosome genes.
      Therefore, this case emerges as an invitation to consider the mosaics of Turner
      syndrome and to study their phenotypes in correlation with their genotypes to
      discover the underlying developmental and genetic mechanisms, especially the ones
      related to sex chromosomes.

PMID- 29196851
TI  - ?

PMID- 29196853
TI  - Immunohistochemical characterization of brush cells in the rat larynx.
AB  - The immunohistochemical characteristics of brush cells in the laryngeal mucosa
      were examined using immunohistochemistry for various immunohistochemical cell
      markers including villin at the light and electron microscopic levels. Cells that
      were immunoreactive to villin were barrel-shaped with thick cytoplasmic processes
      extending toward the lumen of the laryngeal cavity. Immunoelectron microscopic
      observations revealed thick and short microvilli with long rootlets of
      microfilaments. Numerous small clear vesicles and small finger-like cytoplasmic
      processes were observed in the apical process and lateral membrane, respectively.
      Double immunofluorescence showed villin-immunoreactive cells were not
      immunoreactive for the markers of solitary chemosensory cells, GNAT3 and
      phospholipase C, beta2-subunit (PLCbeta2), or for that of neuroendocrine cells,
      synaptosome-associated protein 25kD. Furthermore, immunoreactivities for
      cytokeratin 18 (CK18) and doublecortin like-kinase 1 in the perinuclear cytoplasm
      of villin-immunoreactive cells. However, some CK18-immunoreactive cells were
      immunoreactive to GNAT3 but not to villin. Regarding sensory innervation, only a
      few intraepithelial nerve endings with P2X3, SP, or CGRP immunoreactivity
      attached to villin-immunoreactive cells. In the present study, brush cells in the
      rat laryngeal mucosa were classified by immunoreactivity for villin, and were
      independent of other non-ciliated epithelial cells such as solitary chemosensory
      cells and neuroendocrine cells.

PMID- 29196849
TI  - The phenotypic and molecular assessment of the non-conserved Arabidopsis
      MICRORNA163/S-ADENOSYL-METHYLTRANSFERASE regulatory module during biotic stress.
AB  - In plants, microRNAs (miRNAs) have evolved in parallel to the protein-coding
      genes that they target for expression regulation, and miRNA-directed gene
      expression regulation is central to almost every cellular process. MicroRNA,
      miR163, is unique to the Arabidopsis genus and is processed into a 24-nucleotide
      (nt) mature small regulatory RNA (sRNA) from a single precursor transcript
      transcribed from a single locus, the MIR163 gene. The MIR163 locus is a result of
      a recent inverted duplication event of one of the five closely related S-ADENOSYL
      METHYLTRANSFERASE genes that the mature miR163 sRNA targets for expression
      regulation. Currently, however, little is known about the role of the miR163/S
      ADENOSYL-METHYLTRANSFERASE regulatory module in response to biotic stress. Here,
      we document the expression domains of MIR163 and the S-ADENOSYL-METHYLTRANSFERASE
      target genes following fusion of their putative promoter sequences to the beta
      glucuronidase (GUS) reporter gene and subsequent in planta expression. Further,
      we report on our phenotypic and molecular assessment of Arabidopsis thaliana
      plants with altered miR163 accumulation, namely the mir163-1 and mir163-2
      insertion knockout mutants and the miR163 overexpression line, the MIR163-OE
      plant. Finally, we reveal miR163 accumulation and S-ADENOSYL-METHYLTRANSFERASE
      target gene expression post treatment with the defence elicitors, salicylic acid
      and jasmonic acid, and following Fusarium oxysporum infection, wounding, and
      herbivory attack. Together, the work presented here provides a comprehensive new
      biological insight into the role played by the Arabidopsis genus-specific
      miR163/S-ADENOSYL-METHYLTRANSFERASE regulatory module in normal A. thaliana
      development and during the exposure of A. thaliana plants to biotic stress.

PMID- 29196854
TI  - Fourteen years of progress testing in radiology residency training: experiences
      from The Netherlands.
AB  - OBJECTIVES: To describe the development of the Dutch Radiology Progress Test
      (DRPT) for knowledge testing in radiology residency training in The Netherlands
      from its start in 2003 up to 2016. METHODS: We reviewed all DRPTs conducted since
      2003. We assessed key changes and events in the test throughout the years, as
      well as resident participation and dispensation for the DRPT, test reliability
      and discriminative power of test items. RESULTS: The DRPT has been conducted semi
      annually since 2003, except for 2015 when one digital DRPT failed. Key changes in
      these years were improvements in test analysis and feedback, test digitalization
      (2013) and inclusion of test items on nuclear medicine (2016). From 2003 to 2016,
      resident dispensation rates increased (Pearson's correlation coefficient 0.74, P
      value <0.01) to maximally 16 %. Cronbach's alpha for test reliability varied
      between 0.83 and 0.93. The percentage of DRPT test items with negative item-rest
      correlations, indicating relatively poor discriminative power, varied between 4 %
      and 11 %. CONCLUSIONS: Progress testing has proven feasible and sustainable in
      Dutch radiology residency training, keeping up with innovations in the
      radiological profession. Test reliability and discriminative power of test items
      have remained fair over the years, while resident dispensation rates have
      increased. KEY POINTS: * Progress testing allows for monitoring knowledge
      development from novice to senior trainee. * In postgraduate medical training,
      progress testing is used infrequently. * Progress testing is feasible and
      sustainable in radiology residency training.

PMID- 29196855
TI  - Ultrasound-ultrasound image overlay fusion improves real-time control of
      radiofrequency ablation margin in the treatment of hepatocellular carcinoma.
AB  - OBJECTIVES: To assess the clinical feasibility of US-US image overlay fusion with
      evaluation of the ablative margin in radiofrequency ablation (RFA) for
      hepatocellular carcinoma (HCC). METHODS: Fifty-three patients with 68 HCCs
      measuring 0.9-4.0 cm who underwent RFA guided by US-US overlay image fusion were
      included in this retrospective study. By an overlay of pre-/postoperative US, the
      tumor image could be projected onto the ablative hyperechoic zone. Therefore, the
      ablative margin three-dimensionally could be shown during the RFA procedure. US
      US image overlay was compared to dynamic CT a few days after RFA for assessment
      of early treatment response. Accuracy of graded response was calculated, and the
      performance of US-US image overlay fusion was compared with that of CT using a
      Kappa agreement test. RESULTS: Technically effective ablation was achieved in a
      single session, and 59 HCCs (86.8 %) succeeded in obtaining a 5-mm margin on CT.
      The response with US-US image overlay correctly predicted early CT evaluation
      with an accuracy of 92.6 % (63/68) (k = 0.67; 95 % CI: 0.39-0.95). CONCLUSION: US
      US image overlay fusion can be proposed as a feasible guidance in RFA with a
      safety margin and predicts early response of treatment assessment with high
      accuracy. KEY POINTS: * US-US image overlay fusion visualizes the ablative margin
      during RFA procedure. * Visualizing the margin during the procedure can prompt
      immediate complementary treatment. * US image fusion correlates with the results
      of early evaluation CT.

PMID- 29196856
TI  - Tin-filtered low-dose chest CT to quantify macroscopic calcification burden of
      the thoracic aorta.
AB  - OBJECTIVES: To compare a low-dose, tin-filtered, nonenhanced, high-pitch Sn100
      kVp CT protocol (Sn100) with a standard protocol (STP) for the detection of
      calcifications in the ascending aorta in patients scheduled for cardiac surgery.
      METHODS: Institutional Review Board approval for this retrospective study was
      waived and the study was HIPAA-compliant. The study included 192 patients (128
      men; age 68.8 +/- 9.9 years), of whom 87 received the STP and 105 the Sn100
      protocol. Size-specific dose estimates (SSDE) and radiation doses were obtained
      using dose monitoring software. Two blinded readers evaluated image quality on a
      scale from 1 (low) to 5 (high) and the extent of calcifications of the ascending
      aorta on a scale from 0 (none) to 10 (high), subdivided into 12 anatomic
      segments. RESULTS: The Sn100 protocol achieved a mean SSDE of only 0.5 +/- 0.1
      mGy and 0.20 +/- 0.04 mSv compared with the mean SSDE of 5.4 +/- 2.2 mGy achieved
      with the STP protocol (p < 0.0001). Calcification burden was associated with age
      (p < 0.0001), but was independent of protocol with mean calcification scores of
      0.48 +/- 1.23 (STP) and 0.55 +/- 1.25 (Sn100, p = 0.18). Reader agreement was
      very good (STP kappa = 0.87 +/- 0.02, Sn100 kappa = 0.88 +/- 0.01). The STP
      protocol provided a higher subjective image quality than the Sn100 protocol: STP
      median 4, interquartile range 4-5, vs. SN100 3, 3-4; p < 0.0001) and a slightly
      better depiction of calcification (STP 5, 4-5, vs. Sn100 4, 4-5; p < 0.0001).
      CONCLUSIONS: The optimized Sn100 protocol achieved a mean SSDE of only 0.5 +/-
      0.1 mGy while the depiction of calcifications remained good, and there was no
      systematic difference in calcification burden between the two protocols. KEY
      POINTS: * Tin-filtered, low-dose CT can be used to assess aortic calcifications
      before cardiac surgery * An optimized Sn100 protocol achieved a mean SSDE of only
      0.5 +/- 0.1 mGy * The depiction of atherosclerosis of the thoracic aorta was
      similar with both protocols * The depiction of relevant thoracic pathologies
      before cardiac surgery was similar with both protocols.

PMID- 29196857
TI  - Pulmonary subsolid nodules: value of semi-automatic measurement in diagnostic
      accuracy, diagnostic reproducibility and nodule classification agreement.
AB  - OBJECTIVES: We hypothesized that semi-automatic diameter measurements would
      improve the accuracy and reproducibility in discriminating preinvasive lesions
      and minimally invasive adenocarcinomas from invasive pulmonary adenocarcinomas
      appearing as subsolid nodules (SSNs) and increase the reproducibility in
      classifying SSNs. METHODS: Two readers independently performed semi-automatic and
      manual measurements of the diameters of 102 SSNs and their solid portions.
      Diagnostic performance in predicting invasive adenocarcinoma based on diameters
      was tested using logistic regression analysis with subsequent receiver operating
      characteristic curves. Inter- and intrareader reproducibilities of diagnosis and
      SSN classification according to Fleischner's guidelines were investigated for
      each measurement method using Cohen's kappa statistics. RESULTS: Semi-automatic
      effective diameter measurements were superior to manual average diameters for the
      diagnosis of invasive adenocarcinoma (AUC, 0.905-0.923 for semi-automatic
      measurement and 0.833-0.864 for manual measurement; p<0.05). Reproducibility of
      diagnosis between the readers also improved with semi-automatic measurement
      (kappa=0.924 for semi-automatic measurement and 0.690 for manual measurement,
      p=0.012). Inter-reader SSN classification reproducibility was significantly
      higher with semi-automatic measurement (kappa=0.861 for semi-automatic
      measurement and 0.683 for manual measurement, p=0.022). CONCLUSIONS: Semi
      automatic effective diameter measurement offers an opportunity to improve
      diagnostic accuracy and reproducibility as well as the classification
      reproducibility of SSNs. KEY POINTS: * Semi-automatic effective diameter
      measurement improves the diagnostic accuracy for pulmonary subsolid nodules. *
      Semi-automatic measurement increases the inter-reader agreement on the diagnosis
      for subsolid nodules. * Semi-automatic measurement augments the inter-reader
      reproducibility for the classification of subsolid nodules.

PMID- 29196859
TI  - Validation of simplified postoperative nausea and vomiting intensity scale in
      Taiwan.
AB  - This study determined whether the Simplified Postoperative Nausea and Vomiting
      Impact Scale (SPONVIS), could be used to predict clinically important PONV in
      Taiwanese. In this prospective, observational study, SPONVIS, simplified Apfel
      PONV Risk Scores, post-operative anti-emetic drug use, total PONV score, and 3
      month recall score for PONV were recorded from Taiwanese patients who had
      undergone general anesthesia and surgery. With antiemetic use and 3-month recall
      score as validations of clinical significance, we determined whether the elements
      and cut-off points used in the original SPONVIS study could be used in Taiwanese
      patients. A total of 378 patients were included in the analysis. One hundred
      forty (37.1%) patients had PONV. Forty-eight patients (12.7%) had clinically
      important PONV (SPONVIS score >= 5). The odds ratios were 14.26 (CI 6.91-29.43; P
      < 0.001) and 4.95 (CI 2.42 to 10.11; P < 0.001), respectively, for prediction of
      anti-emetic drug use and 3-month recall. The SPONVIS and its construct elements
      were significantly related to anti-emetic drug use, 3-month recall score for
      PONV, total PONV score, and Apfel risk score (all P <= 0.005), results similar to
      those reported in the original Australian PONV impact score study. The SPONVIS
      cut-off points 3 and 5 were statistically significant predictors of anti-emetic
      drug use. However, a cut-off point of 3 had a higher OR (24.08) than a cut-off of
      5 (14.26) for prediction of anti-emetic drug use. SPONVIS and both construct
      elements (the nausea and vomiting impact scores) are useful predictors of
      clinically important PONV in Taiwanese.

PMID- 29196858
TI  - First Trimester Prenatal Care Initiation Among Hispanic Women Along the U.S.
      Mexico Border.
AB  - Background First trimester prenatal care (FTPNC) is associated with improved
      birth outcomes. U.S.-Mexico border Hispanic women have lower FTPNC than non
      border or non-Hispanic women. This study aimed to identify (1) what demographic,
      knowledge and care-seeking factors influence FTPNC among Hispanic women in border
      counties served by five Healthy Start sites, and (2) what FTPNC barriers may be
      unique to this target population. Healthy Starts work to eliminate disparities in
      perinatal health in areas with high poverty and poor birth outcomes. Methods 403
      Hispanic women of reproductive age in border communities of California, Arizona,
      New Mexico and Texas were surveyed on knowledge and behaviors related to prenatal
      care (PNC) and basic demographic information. Chi square analyses and logistic
      regressions were used to identify important relationships. Results Chi square
      analyses revealed that primiparous women were significantly less likely to start
      FTPNC than multiparous women (chi2 = 6.8372, p = 0.0089). Women with accurate
      knowledge about FTPNC were more likely to obtain FTPNC (chi2 = 29.280, p < .001)
      and more likely to have seen a doctor within the past year (chi2 = 5.550, p =
      .018). Logistic regression confirmed that multiparity was associated with FTPNC
      and also that living in Texas was negatively associated with FTPNC (R2 = 0.066,
      F(9,340) = 2.662, p = .005). Among 27 women with non-FTPNC, barriers included
      late pregnancy recognition (n = 19) and no medical insurance (n = 5). Conclusions
      This study supports research that first time pregnancies have lower FTPNC, and
      demonstrated a strong association between delayed PNC and late pregnancy
      recognition. Strengthened investments in preconception planning could improve
      FTPNC in this population.

PMID- 29196860
TI  - Role of Thrombin in Soluble Thrombomodulin-Induced Suppression of Peripheral
      HMGB1-Mediated Allodynia in Mice.
AB  - High mobility group box 1 (HMGB1), a nuclear protein, once released into the
      extracellular space under pathological conditions, plays a pronociceptive role in
      redox-dependent distinct active forms, all-thiol HMGB1 (at-HMGB1) and disulfide
      HMGB1 (ds-HMGB1), that accelerate nociception through the receptor for advanced
      glycation endproducts (RAGE) and Toll-like receptor 4 (TLR4), respectively.
      Thrombomodulin (TM), an endothelial membrane protein, and soluble TM, known as
      TMalpha, promote thrombin-mediated activation of protein C and also sequester
      HMGB1, which might facilitate thrombin degradation of HMGB1. The present study
      aimed at clarifying the role of thrombin in TMalpha-induced suppression of
      peripheral HMGB1-dependent allodynia in mice. Thrombin-induced degradation of at
      HMGB1 and ds-HMGB1 was accelerated by TMalpha in vitro. Intraplantar (i.pl.)
      injection of bovine thymus-derived HMGB1 in an unknown redox state, at-HMGB1, ds
      HMGB1 or lipopolysaccharide (LPS), known to cause HMGB1 secretion, produced long
      lasting mechanical allodynia in mice, as assessed by von Frey test. TMalpha, when
      preadministered i.pl., prevented the allodynia caused by bovine thymus-derived
      HMGB1, at-HMGB1, ds-HMGB1 or LPS, in a dose-dependent manner. The TMalpha-induced
      suppression of the allodynia following i.pl. at-HMGB1, ds-HMGB1 or LPS was
      abolished by systemic preadministration of argatroban, a thrombin-inhibiting
      agent, and accelerated by i.pl. co-administered thrombin. Our data clearly
      indicate that TMalpha is capable of promoting the thrombin-induced degradation of
      both at-HMGB1 and ds-HMGB1, and suppresses the allodynia caused by either HMGB1
      in a thrombin-dependent manner. Considering the emerging role of HMGB1 in
      distinct pathological pain models, the present study suggests the therapeutic
      usefulness of TMalpha for treatment of intractable and/or persistent pain.

PMID- 29196863
TI  - School Age Outcomes of Children with Autism Spectrum Disorder Who Received
      Community-Based Early Interventions.
AB  - This study followed children with Autism Spectrum Disorder (ASD) from early
      intervention into their early schooling years, when they were aged between 6 and
      9 years, on autism symptom severity and cognitive functioning. The children,
      matched at pre-intervention, were compared on type of community provided service:
      31 were in receipt of community-based group Early Start Denver Model and 28 had
      received other community provisions for ASD. Irrespective of groups, cognitive
      functioning was found to have significantly improved by school age compared to
      pre-intervention. Autism symptom severity increased during the same developmental
      period, seemingly driven by an increase in restricted and repetitive behaviours
      over time. In contrast, both groups displayed improved social affect by school
      age.

PMID- 29196862
TI  - Voluntary exposure to a toxin: the genetic influence on ethanol consumption.
AB  - Ethyl alcohol is a toxin that, when consumed at high levels, produces organ
      damage and death. One way to prevent or ameliorate this damage in humans is to
      reduce the exposure of organs to alcohol by reducing alcohol ingestion. Both the
      propensity to consume large volumes of alcohol and the susceptibility of human
      organs to alcohol-induced damage exhibit a strong genetic influence. We have
      developed an integrative genetic/genomic approach to identify transcriptional
      networks that predispose complex traits, including propensity for alcohol
      consumption and propensity for alcohol-induced organ damage. In our approach, the
      phenotype is assessed in a panel of recombinant inbred (RI) rat strains, and
      quantitative trait locus (QTL) analysis is performed. Transcriptome data from
      tissues/organs of naive RI rat strains are used to identify transcriptional
      networks using Weighted Gene Coexpression Network Analysis (WGCNA). Correlation
      of the first principal component of transcriptional coexpression modules with the
      phenotype across the rat strains, and overlap of QTLs for the phenotype and the
      QTLs for the coexpression modules (module eigengene QTL) provide the criteria for
      identification of the functionally related groups of genes that contribute to the
      phenotype (candidate modules). While we previously identified a brain
      transcriptional module whose QTL overlapped with a QTL for levels of alcohol
      consumption in HXB/BXH RI rat strains and 12 selected rat lines, this module did
      not account for all of the genetic variation in alcohol consumption. Our search
      for QTL overlap and correlation of coexpression modules with phenotype can,
      however, be applied to any organ in which the transcriptome has been measured,
      and this represents a holistic approach in the search for genetic contributors to
      complex traits. Previous work has implicated liver/brain interactions,
      particularly involving inflammatory/immune processes, as influencing alcohol
      consumption levels. We have now analyzed the liver transcriptome of the HXB/BXH
      RI rat panel in relation to the behavioral trait of alcohol consumption. We used
      RNA-Seq and microarray data to construct liver transcriptional networks, and
      identified a liver candidate transcriptional coexpression module that explained
      24% of the genetic variance in voluntary alcohol consumption. The transcripts in
      this module focus attention on liver secretory products that influence
      inflammatory and immune signaling pathways. We propose that these liver secretory
      products can interact with brain mechanisms that affect alcohol consumption, and
      targeting these pathways provides a potential approach to reducing high levels of
      alcohol intake and also protecting the integrity of the liver and other organs.

PMID- 29196861
TI  - CRISPR-based strategies for studying regulatory elements and chromatin structure
      in mammalian gene control.
AB  - The development of high-throughput methods has enabled the genome-wide
      identification of putative regulatory elements in a wide variety of mammalian
      cells at an unprecedented resolution. Extensive genomic studies have revealed the
      important role of regulatory elements and genetic variation therein in disease
      formation and risk. In most cases, there is only correlative evidence for the
      roles of these elements and non-coding changes within these elements in
      pathogenesis. With the advent of genome- and epigenome-editing tools based on the
      CRISPR technology, it is now possible to test the functional relevance of the
      regulatory elements and alterations on a genomic scale. Here, we review the
      various CRISPR-based strategies that have been developed to functionally validate
      the candidate regulatory elements in mammals as well as the non-coding genetic
      variants found to be associated with human disease. We also discuss how these
      synthetic biology tools have helped to elucidate the role of three-dimensional
      nuclear architecture and higher-order chromatin organization in shaping
      functional genome and controlling gene expression.

PMID- 29196864
TI  - Choosing an Appropriate Physical Exercise to Reduce Stereotypic Behavior in
      Children with Autism Spectrum Disorders: A Non-randomized Crossover Study.
AB  - Considerable evidence has shown that physical exercise could be an effective
      treatment in reducing stereotypical autism spectrum disorder (ASD) behaviors in
      children. The present study seeks to examine the underlying mechanism by
      considering the theoretical operant nature of stereotypy. Children with ASD (n =
      30) who exhibited hand-flapping and body-rocking stereotypies were asked to
      participate in both control (story-time) and experimental (ball-tapping-exercise
      intervention) conditions. The experimental condition comprised 15 min of ball
      tapping during which the children were asked to tap a plastic ball as many times
      as they could. Results indicated that hand-flapping stereotypy was significantly
      reduced but body-rocking stereotypy following the ball-tapping-exercise
      intervention was not. These results not only confirm the positive impact of
      exercise intervention on stereotypic behavior as shown in many previous studies,
      but further suggest that physical exercise should be matched with the
      biomechanics of stereotypy to produce a desirable behavioral benefit.

PMID- 29196865
TI  - Parent Perceptions of Psychosocial Outcomes of Equine-Assisted Interventions for
      Children with Autism Spectrum Disorder.
AB  - This research explored parents' perceptions of the psychosocial outcomes of their
      children's experience of receiving equine-assisted interventions (EAI).
      Participants were the parents of six children (aged 3-14) diagnosed with autism
      spectrum disorder. Five semi-structured interviews were conducted and the
      transcript data was analysed using Interpretative phenomenological analysis. Four
      super-ordinate themes emerged from the analysis: (1) child's improved self
      concept and enhanced emotional well-being, (2) child's improved self-regulatory
      ability, (3) social benefits for the child, and (4) unexpected outcomes. EAI was
      perceived by the parents as having several levels of psychosocial benefits for
      their children. These benefits may also extend to parents and family through
      ecopsychological and "flow on" effects associated with the children's involvement
      in EAI programs.

PMID- 29196866
TI  - Reducing Bottlenecks to Improve the Efficiency of the Lung Cancer Care Delivery
      Process: A Process Engineering Modeling Approach to Patient-Centered Care.
AB  - The process of lung cancer care from initial lesion detection to treatment is
      complex, involving multiple steps, each introducing the potential for substantial
      delays. Identifying the steps with the greatest delays enables a focused effort
      to improve the timeliness of care-delivery, without sacrificing quality. We
      retrospectively reviewed clinical events from initial detection, through
      histologic diagnosis, radiologic and invasive staging, and medical clearance, to
      surgery for all patients who had an attempted resection of a suspected lung
      cancer in a community healthcare system. We used a computer process modeling
      approach to evaluate delays in care delivery, in order to identify potential
      'bottlenecks' in waiting time, the reduction of which could produce greater care
      efficiency. We also conducted 'what-if' analyses to predict the relative impact
      of simulated changes in the care delivery process to determine the most efficient
      pathways to surgery. The waiting time between radiologic lesion detection and
      diagnostic biopsy, and the waiting time from radiologic staging to surgery were
      the two most critical bottlenecks impeding efficient care delivery (more than 3
      times larger compared to reducing other waiting times). Additionally, instituting
      surgical consultation prior to cardiac consultation for medical clearance and
      decreasing the waiting time between CT scans and diagnostic biopsies, were
      potentially the most impactful measures to reduce care delays before surgery.
      Rigorous computer simulation modeling, using clinical data, can provide useful
      information to identify areas for improving the efficiency of care delivery by
      process engineering, for patients who receive surgery for lung cancer.

PMID- 29196868
TI  - The proteasome and proteasome inhibitors in multiple myeloma.
AB  - Proteasome inhibitors are one of the most important classes of agents to have
      emerged for the treatment of multiple myeloma in the past two decades, and now
      form one of the backbones of treatment. Three agents in this class have been
      approved by the United States Food and Drug Administration-the first-in-class
      compound bortezomib, the second-generation agent carfilzomib, and the first oral
      proteasome inhibitor, ixazomib. The success of this class of agents is due to the
      exquisite sensitivity of myeloma cells to the inhibition of the 26S proteasome,
      which plays a critical role in the pathogenesis and proliferation of the disease.
      Proteasome inhibition results in multiple downstream effects, including the
      inhibition of NF-kappaB signaling, the accumulation of misfolded and unfolded
      proteins, resulting in endoplasmic reticulum stress and leading to the unfolded
      protein response, the downregulation of growth factor receptors, suppression of
      adhesion molecule expression, and inhibition of angiogenesis; resistance to
      proteasome inhibition may arise through cellular responses mediating these
      downstream effects. These multiple biologic consequences of proteasome inhibition
      result in synergistic or additive activity with other chemotherapeutic and
      targeted agents for myeloma, and proteasome inhibitor-based combination regimens
      have become established as a cornerstone of therapy throughout the myeloma
      treatment algorithm, incorporating agents from the other key classes of
      antimyeloma agents, including the immunomodulatory drugs, monoclonal antibodies,
      and histone deacetylase inhibitors. This review gives an overview of the critical
      role of the proteasome in myeloma and the characteristics of the different
      proteasome inhibitors and provides a comprehensive summary of key clinical
      efficacy and safety data with the currently approved proteasome inhibitors.

PMID- 29196867
TI  - Prevalence of haptic feedback in robot-mediated surgery: a systematic review of
      literature.
AB  - With the successful uptake and inclusion of robotic systems in minimally invasive
      surgery and with the increasing application of robotic surgery (RS) in numerous
      surgical specialities worldwide, there is now a need to develop and enhance the
      technology further. One such improvement is the implementation and amalgamation
      of haptic feedback technology into RS which will permit the operating surgeon on
      the console to receive haptic information on the type of tissue being operated
      on. The main advantage of using this is to allow the operating surgeon to feel
      and control the amount of force applied to different tissues during surgery thus
      minimising the risk of tissue damage due to both the direct and indirect effects
      of excessive tissue force or tension being applied during RS. We performed a two
      rater systematic review to identify the latest developments and potential avenues
      of improving technology in the application and implementation of haptic feedback
      technology to the operating surgeon on the console during RS. This review
      provides a summary of technological enhancements in RS, considering different
      stages of work, from proof of concept to cadaver tissue testing, surgery in
      animals, and finally real implementation in surgical practice. We identify that
      at the time of this review, while there is a unanimous agreement regarding need
      for haptic and tactile feedback, there are no solutions or products available
      that address this need. There is a scope and need for new developments in haptic
      augmentation for robot-mediated surgery with the aim of improving patient care
      and robotic surgical technology further.

PMID- 29196870
TI  - Changes in birth-related pain perception impact of neurobiological and psycho
      social factors.
AB  - PURPOSE: To analyse post-partum short- and long-term pain sensitivity and the
      influence of endogenous pain inhibition as well as distinct psycho-social factors
      on birth-related pain. METHODS: Pain sensitivity was assessed in 91 primiparous
      women at three times: 2-6 weeks before, one to 3 days as well as ten to 14 weeks
      after childbirth. Application of a pressure algometer in combination with a cold
      pressor test was utilised for measurement of pain sensitivity and assessment of
      conditioned pain modulation (CPM). Selected psycho-social factors (anxiety,
      social support, history of abuse, chronic pain and fear of childbirth) were
      evaluated with standardised questionnaires and their effect on pain processing
      then analysed. RESULTS: Pressure pain threshold, cold pain threshold and cold
      pain tolerance increased significantly directly after birth (all p < 0.001).
      While cold pain parameters partly recovered on follow-up, pressure pain threshold
      remained increased above baseline (p < 0.001). These pain-modulating effects were
      not found for women with history of abuse. While CPM was not affected by birth,
      its extent correlated significantly (r = 0.367) with the drop in pain sensitivity
      following birth. Moreover, high trait anxiety predicted an attenuated reduction
      in pain sensitivity (r = 0.357), while there was no correlation with fear of
      childbirth, chronic pain and social support. CONCLUSION: Pain sensitivity showed
      a decrease when comparing post-partum with prepartum values. The extent and
      direction of CPM appear to be a trait variable that predicted post-partum
      hypalgesia without being changed itself. Post-partum hypalgesia was reduced in
      women with a history of abuse and high trait anxiety, which suggests that
      individual differences in CPM affect childbirth experience.

PMID- 29196869
TI  - Circulating levels of specific members of chromosome 19 microRNA cluster are
      associated with preeclampsia development.
AB  - PURPOSE: To perform serum microRNA expression profiling to identify members of
      chromosome 19 miRNA cluster involved in preeclampsia development. METHODS: Serum
      chromosome 19 miRNA cluster microRNA expression profiling was evaluated at 12,
      16, and 20 gestational weeks and at the time of preeclampsia diagnosis, in women
      who developed preeclampsia (WWD-PE; n = 16) and controls (n = 18) using TaqMan
      low density array plates. RESULTS: A total of 51 chromosome 19 microRNA cluster
      members were evaluated. The circulating hsa-miRs 512-3p, 518f-3p, 520c-3p, and
      520d-3p, were differentially expressed between groups (P < 0.05). Compared with
      controls, serum levels of hsa-miR-518f-3p at 20 GW were useful for identifying
      WWD-Mild-PE (P = 0.035) and WWD-Severe-PE (P = 0.007). CONCLUSIONS: Serum hsa
      miRs 512-3p, 518f-3p, 520c-3p, and 520d-3p, are differentially expressed between
      WWD-PE and controls and their role in the development of preeclampsia should be
      investigated further.

PMID- 29196871
TI  - Three cases of metallosis associated with spine instrumentation.
AB  - The characteristic trait of metallosis is the presence of tissue staining.
      Analyzing explanted revision hardware from spine surgeries and performing
      ICPMS/AES analysis on removed tissue samples, a clinically relevant definition
      for metallosis may be developed. Results of the analysis identified hardware
      fretting wear and corrosion, and ICP-MS/AES analysis identified elevated metal
      ion concentrations in all cases. This supports the hypothesis that corrosion may
      be linked to poor health outcomes and potential need for revision surgery. Using
      failure analysis methods, corrosion products from orthopedic spine implants can
      be identified to begin to characterize metallosis in a clinically relevant
      manner. Failure analysis for patients undergoing revision spine surgery for other
      causes. Using failure analysis methods we conducted a retrieval analysis of
      explanted hardware and tissue. Implant failure with surrounding tissue metal
      staining is a current issue in the field of orthopedics. Specifically in spine,
      this issue is under reported and over looked as a clinically significant finding.
      Metallosis is most commonly used to describe the presence of tissue staining
      however this is not a clinically relevant definition. There is a need for further
      research to provide a better understanding of metallosis leading to better
      patient outcomes. Patients were screened for this study during a radiological
      review prior to surgery. All explanted hardware was documented and inspected for
      signs of wear and corrosion using non-destructive testing. A tissue sample that
      is normally removed and discarded was collected for ICP-MS/AES analysis. The
      presence of fretting corrosion, galling and corrosion fatigue was found on all
      explanted hardware. Cr levels are significantly higher than what was previously
      published as normal in muscle 0.03  MUg/g. One case was a 4 order of magnitude
      elevation with the other 2 approximately 2 orders of magnitude increase. Titanium
      and Co concentrations are also significantly increased. The Ca to P ratio for all
      samples is approximately 1.7:1 suggesting some form of apatitic crystal present
      due to drying of the tissues. In all cases, the Al, Mo, V, Co, content in
      surrounding tissue is significantly elevated >10* above "normal," 8.4 +/- 4.8;
      1.61 +/- 1.41; 0.06 +/- 0.03; 1.35 +/- 1.97 MUg/g respectively. A "normal"
      reference titanium level could only be found for whole blood, 0.00072 +/- 0.1412
      MU/g. Iron and Ni measurements are within typical values presented in previous
      studies. No single mechanism for the release of metal ion in a patient is clear.
      Evidence suggests a tribocorrosive process due to both wear and environmental
      factors. Specific biologic mechanisms, such as the possible presence of bacteria
      may affect the fretting and corrosion of spinal instrumentation must be explored
      in conjunction with thorough review of patient outcomes. Such an effort can
      potentially reduce patient readmission and increase successful patient outcomes.

PMID- 29196872
TI  - Seleno-compounds and Carnosic Acid Added to Diets with Rapeseed and Fish Oils
      Affect Concentrations of Selected Elements and Chemical Composition in the Liver,
      Heart and Muscles of Lambs.
AB  - The objective of our studies was to investigate effects of carnosic acid (CA),
      selenized yeast (SeY) and selenate (SeVI) added to the diet including rapeseed
      oil (RO) and fish oil (FO) on concentrations of elements, fatty acids (FAs),
      tocopherols, cholesterol, and malondialdehyde in the liver, heart, musculus
      longissimus dorsi (MLD), and musculus biceps femoris (MBF) of lambs. Lambs were
      fed diets: group I-the basal diet (BD) with RO; group II-BD with RO and FO; group
      III-BD with RO, FO, and CA; group IV-BD with RO, FO, CA, and SeY; group V-BD with
      RO, FO, CA, and SeVI. The diets with Se compounds increased Se concentrations in
      all tissues compared with other diets. The diet with SeVI increased Cd, Sb, and
      Pb concentrations in the liver compared to groups I, II, and IV. The diets
      containing Se compounds increased Sb and Pb concentrations in MBF compared to
      groups I and II. All diets with CA reduced As, Sb, and Pb concentrations in MLD
      compared to groups I and II. All diets with FO increased concentrations of FAs
      and malondialdehyde in the liver compared to group I. All diets with FO decreased
      FAs concentrations in MBF compared to group I. The diets containing CA
      with/without Se compounds increased malondialdehyde concentrations in MBF
      compared to groups I and II. The diet with Se compounds reduced malondialdehyde
      concentrations in MLD compared to group II. All diets with FO changed
      concentrations of tocopherols and cholesterol in all tissues compared to group I.
      Our study showed that the addition of SeY or SeVI to the experimental diet
      increased the concentration of Se in all assayed tissues of lambs without
      adversely influencing performance or causing physiological disorders in internal
      organs. Both, SeY or SeVI added to the experimental diet decreased the oxidative
      stress and the concentrations of As, Sb, and Pb in MLD compared with the diets
      containing RO, irrespective of the presence of FO (groups I and II). Our study
      provides useful knowledge for nutritionists carrying out further investigations
      aimed at improving farm animal health, performance, and the nutritional quality
      of animal products for humans.

PMID- 29196873
TI  - Total Mercury Determination in Muscle and Liver Tissue Samples from Brazilian
      Amazon Fish Using Slurry Sampling.
AB  - This paper presents a slurry sampling method for total mercury determination by
      graphite furnace atomic absorption spectrometry (GFAAS) in tissue of fish from
      the Amazon. The tissue samples were lyophilized and macerated, and then the
      slurry samples were prepared by putting 20 mg of tissue, added to a solution
      containing Triton X-100, Suprapur HNO3, and zirconium nitrate directly in
      sampling vials of a spectrometer. Mercury standard solutions were prepared under
      the same conditions as the slurry samples. The slurry samples and the mercury
      standard solutions were sonicated for 20 s. Twenty microliters of slurry samples
      were injected into the graphite tube, which contained an internal wall lined with
      tungsten carbide. Under these conditions, it was possible to thermally stabilize
      the mercury up to an atomization temperature of 1700  degrees C. The method was
      validated by mercury determination in reference materials DORM-4 and DOLT-4. The
      LOD and LOQ were 0.014 and 0.045 mg kg-1, respectively, and recovery percentages
      in relation to the concentration values were certified in the order of 98%.

PMID- 29196875
TI  - Correction to: Associations between attention-deficit/hyperactivity disorder and
      autoimmune diseases are modified by sex: a population-based cross-sectional
      study.
AB  - The article "Associations between attention-deficit/hyperactivity disorder and
      autoimmune diseases are modified by sex: a population-based cross-sectional
      study", written by Tor-Arne Hegvik, Johanne Telnes Instanes, Jan Haavik, Kari
      Klungsoyr and Anders Engeland, was originally published electronically on the
      publisher's internet portal (currently SpringerLink) on October 5, 2017 without
      open access due to an error by the Springer editorial office in the processing of
      this article. The authors had originally opted for open access.

PMID- 29196874
TI  - Upregulation of Spinal Voltage-Dependent Anion Channel 1 Contributes to Bone
      Cancer Pain Hypersensitivity in Rats.
AB  - Voltage-dependent anion channel 1 (VDAC1) is thought to contribute to the
      progression of tumor development. However, whether VDAC1 contributes to bone
      cancer pain remains unknown. In this study, we found that the expression of VDAC1
      was upregulated in the L2-5 segments of the spinal dorsal horn at 2 and 3 weeks
      after injection of tumor cells into the tibial cavity. Intrathecal injection of a
      VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the
      over-expression of Toll-like receptor 4 (TLR4). Intrathecal injection of
      minocycline, an inhibitor of microglia, also attenuated the pain hypersensitivity
      of rat models of bone cancer pain. These results suggest that VDAC1 plays a
      significant role in the development of complicated cancer pain, possibly by
      regulating the expression of TLR4.

PMID- 29196876
TI  - Early recognition of sudden cardiac arrest in athletes during sports activity.
AB  - INTRODUCTION: Sudden cardiac arrest (SCA) in athletes is an unexpected life
      threatening event, which is often not recognised early and cardiopulmonary
      resuscitation (CPR) is not always initiated immediately. We describe key features
      to rapidly recognise non-traumatic SCA in athletes during sports activity.
      METHODS: We reviewed videos and images of athletes suffering from non-traumatic
      SCA during sports activity. We searched Google images, Google videos and
      YouTube.com using the keywords 'sudden cardiac death athlete' and 'resuscitation
      athlete'. We analysed (1) the athlete's performance before syncope, (2) the
      athlete's performance at the start of syncope, (3) the position of the body, and
      (4) the athlete's facial expressions before CPR. We analysed our data by
      describing these four features to answer our research question. RESULTS: We
      analysed the sequence of events in six well-known soccer players in whom a camera
      witnessed non-traumatic SCA occurred during their athletic activity. All six
      athletes showed no changes before syncope. Four became unstable while standing
      and unexpectedly collapsed falling on their back. Two suddenly 'dropped dead' and
      fell face down. All six had their eyes wide open with a fixed gaze and fixed
      pupils. CONCLUSIONS: Sudden unexpected loss of consciousness in an athlete in
      action and a fixed gaze eye position are key features of SCA. Immediate cardiac
      massage should follow. The described features to immediately recognise SCA in
      athletes during sports activity should be taught to everyone involved in athletic
      activity leading to earlier recognition of SCA followed by earlier CPR.

PMID- 29196877
TI  - Gold open access: the best of both worlds.
AB  - Gold open access provides free distribution of trustworthy scientific knowledge
      for everyone. As publication modus, it has to withstand the bad reputation of
      predatory journals and overcome the preconceptions of those who believe that open
      access is synonymous with poor quality articles and high costs. Gold open access
      has a bright future and will serve the scientific community, clinicians without
      academic affiliations and the general public.

PMID- 29196878
TI  - Gut microbiome production of short-chain fatty acids and obesity in children.
AB  - Obesity has been a worldwide multifactorial epidemic malady for the last 2
      decades. Changes in gut microbiota composition and its metabolites - short-chain
      fatty acids (SCFAs) - have been associated with obesity. Recent evidence suggests
      that SCFAs made by the gut microbiota may regulate directly or indirectly
      physiological and pathological processes in relation to obesity. We review the
      influence of gut microbiota in energy, glucose, and lipid homeostasis control via
      their metabolites. Gut microbial disturbances in obese children may have a role
      in their metabolism. At first glance, excessive short-chain fatty acids produced
      by a particular gut microbiota represent an additional energy source, and should
      cause an imbalance in energy regulation, contributing to obesity. However,
      simultaneously, SCFA participates in glucose-stimulated insulin secretion from
      the pancreatic beta-cells through interaction with the FFA2 and FFA3 receptors,
      and release of peptide hormones which control appetite. This apparent
      contradictory situation may indicate the involvement of additional particular
      bacteria or bacterial components or metabolites that may trigger regulatory
      cascades by interaction with some G-protein-coupled membrane receptors.

PMID- 29196879
TI  - The feasibility of physiologically based pharmacokinetic modeling in forensic
      medicine illustrated by the example of morphine.
AB  - In forensic medicine, expert opinion is often required concerning dose and time
      of intake of a substance, especially in the context of fatal intoxications. In
      the present case, a 98-year-old man died 4 days after admission to a hospital due
      to a femur neck fracture following a domestic fall in his retirement home. As he
      had obtained high morphine doses in the context of palliative therapy and a
      confusion of his supplemental magnesium tablets with a diuretic by the care
      retirement home was suspected by the relatives, a comprehensive postmortem
      examination was performed. Forensic toxicological GC- and LC-MS analyses
      revealed, besides propofol, ketamine, and a metamizole metabolite in blood and
      urine, toxic blood morphine concentrations of approximately 3 mg/l in femoral and
      5 mg/l in heart blood as well as 2, 7, and 10 mg/kg morphine in brain, liver, and
      lung, respectively. A physiologically based pharmacokinetic (PBPK) model was
      developed and applied to examine whether the morphine concentrations were (i) in
      agreement with the morphine doses documented in the clinical records or (ii) due
      to an excessive morphine administration. PBPK model simulations argue against an
      overdosing of morphine. The immediate cause of death was respiratory and
      cardiovascular failure due to pneumonia following a fall, femur neck fracture,
      and immobilization accompanied by a high and probably toxic concentration of
      morphine, attributable to the administration under palliative care conditions.
      The presented case indicates that PBPK modeling can be a useful tool in forensic
      medicine, especially in question of a possible drug overdosing.

PMID- 29196880
TI  - Role of intestinal Hsp70 in barrier maintenance: contribution of milk to the
      induction of Hsp70.2.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a gastrointestinal disease of
      complex etiology resulting in devastating systemic inflammation and often death
      in premature newborns. We previously demonstrated that formula feeding inhibits
      ileal expression of heat shock protein-70 (Hsp70), a critical stress protein
      within the intestine. Barrier function for the premature intestine is critical.
      We sought to determine whether reduced Hsp70 protein expression increases
      neonatal intestinal permeability. METHODS: Young adult mouse colon cells (YAMC)
      were utilized to evaluate barrier function as well as intestine from Hsp70-/-
      pups (KO). Sections of intestine were analyzed by Western blot,
      immunohistochemistry, and real time PCR. YAMC cells were sub-lethally heated or
      treated with expressed milk (EM) to induce Hsp70. RESULTS: Immunostaining
      demonstrates co-localized Hsp70 and tight junction protein zona occludens-1 (ZO
      1), suggesting physical interaction to protect tight junction function. The
      permeability of YAMC monolayers increases following oxidant injury and is
      partially blocked by Hsp70 induction either by prior heat stress or EM. RT-PCR
      analysis demonstrated that the Hsp70 isoforms, 70.1 and 70.3, predominate in WT
      pup; however, Hsp70.2 predominates in the KO pups. While Hsp70 is present in WT
      milk, it is not present in KO EM. Hsp70 associates with ZO-1 to maintain
      epithelial barrier function. CONCLUSION: Both induction of Hsp70 and exposure to
      EM prevent stress-induced increased permeability. Hsp70.2 is present in both WT
      and KO neonatal intestine, suggesting a crucial role in epithelial integrity.
      Induction of the Hsp70.2 isoform appears to be mediated by mother's milk. These
      results suggest that mother's milk feeding modulates Hsp70.2 expression and could
      attenuate injury leading to NEC. LEVEL OF EVIDENCE: Level III.

PMID- 29196881
TI  - Gata-6 expression is decreased in diaphragmatic and pulmonary mesenchyme of fetal
      rats with nitrofen-induced congenital diaphragmatic hernia.
AB  - PURPOSE: Congenital diaphragmatic hernia (CDH) and associated pulmonary
      hypoplasia are thought to be caused by a malformation of the underlying
      diaphragmatic and airway mesenchyme. GATA binding protein 6 (Gata-6) is a zinc
      finger-containing transcription factor that plays a crucial role during diaphragm
      and lung development. In the primordial diaphragm, Gata-6 expression is
      restricted to mesenchymal compartments of the pleuroperitoneal folds (PPFs). In
      addition, Gata-6 is essential for airway branching morphogenesis through
      upregulation of mesenchymal signaling. Recently, mutations in Gata-6 have been
      linked to human CDH. We hypothesized that diaphragmatic and pulmonary Gata-6
      expression is decreased in the nitrofen-induced CDH model. METHODS: Time-mated
      rats were exposed to either nitrofen or vehicle on gestational day 9 (D9). Fetal
      diaphragms (n = 72) and lungs (n = 48) were microdissected on selected timepoints
      D13, D15 and D18, and divided into control and nitrofen-exposed specimens (n = 12
      per sample, timepoint and experimental group, respectively). Diaphragmatic and
      pulmonary gene expression of Gata-6 was analyzed by qRT-PCR. Immunofluorescence
      double staining for Gata-6 was combined with the diaphragmatic mesenchymal marker
      Gata-4 and the pulmonary mesenchymal marker Fgf-10 to evaluate protein expression
      and localization in fetal diaphragms and lungs. RESULTS: Relative mRNA expression
      levels of Gata-6 were significantly decreased in PPFs on D13 (0.57 +/- 0.21 vs.
      2.27 +/- 1.30; p < 0.05), developing diaphragms (0.94 +/- 0.59 vs. 2.28 +/- 1.89;
      p < 0.05) and lungs (0.56 +/- 0.16 vs. 0.71 +/- 0.39; p < 0.05) on D15 and fully
      muscularized diaphragms (1.20 +/- 1.10 vs. 2.52 +/- 1.86; p < 0.05) and
      differentiated lungs (0.56 +/- 0.05 vs. 0.77 +/- 0.14; p < 0.05) on D18 of
      nitrofen-exposed fetuses compared to controls. Confocal laser scanning microscopy
      demonstrated markedly diminished immunofluorescence of Gata-6 mainly in
      diaphragmatic and pulmonary mesenchyme, which was associated with a reduction of
      proliferating mesenchymal cells in nitrofen-exposed fetuses on D13, D15, and D18
      compared to controls. CONCLUSION: Decreased Gata-6 expression during
      diaphragmatic development and lung branching morphogenesis may disrupt
      mesenchymal cell proliferation, causing malformed PPFs and reduced airway
      branching, thus leading to diaphragmatic defects and pulmonary hypoplasia in the
      nitrofen-induced CDH model.

PMID- 29196882
TI  - The GABRB3 Polymorphism and its Association with Schizophrenia.
AB  - The aim of this study was to explore whether schizophrenia occurrence is
      associated with polymorphisms in the 5' regulatory region of GABRB3 (gamma
      aminobutyric acid type A receptor beta 3, subunit gene). The study included 324
      patients with schizophrenia and 327 unaffected participants; all individuals were
      northern Han Chinese. Genotype and haplotype frequency distributions were
      compared for the 2 groups by means of PCR amplification and direct sequencing of
      the promoter region of GABRB3. The genotype distribution among control
      participants was in accordance with the Hardy-Weinberg equilibrium. Five common
      single-nucleotide polymorphism (SNP) sites were detected in the 5' promoter
      region of GABRB3: rs4243768, rs7171660, rs4363842, rs4906902, and rs8179184. Only
      rs8179184 and rs4906902 differed significantly in frequency between controls and
      cases (P < 0.05); this difference remained significant when only women in each
      group were compared. The 2 SNP sites showed linkage disequilibrium, resulting in
      2 haplotypes: T-G and C-A. The frequency of C-A was significantly higher among
      patients with schizophrenia than among controls. Our findings suggest that
      rs4906902 and rs8179184 in the 5' promoter region of GABRB3 are associated with
      schizophrenia. The C-A haplotype may entail an increased risk of schizophrenia,
      and the onset of schizophrenia may be gender-specific.

PMID- 29196883
TI  - Magnesium Lithospermate B Suppresses Lipopolysaccharide-Induced Neuroinflammation
      in BV2 Microglial Cells and Attenuates Neurodegeneration in Lipopolysaccharide
      Injected Mice.
AB  - Chronic inflammation in the brain plays a critical role in major
      neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease
      (PD), and multiple sclerosis (MS). Microglia, the resident macrophages and
      intrinsic components of the central nervous system (CNS), appear to be the main
      effectors in this pathological process. Magnesium lithospermate B (MLB) is one of
      the major bioactive components of Radix Salviae miltiorrhizae, which has been
      documented to protect neurons against multiple types of neuronal injury. However,
      its functions on microglia and the related neuroinflammation remain unknown. In
      the present study, BV2 microglial cells were used to assess the anti
      neuroinflammatory capacity of MLB. Our data show that treatment with MLB could
      not only suppress lipopolysaccharide (LPS)-induced proliferation and
      morphological changes, but also interfere with cell cycle progression in BV2
      cells. More strikingly, it attenuated the production of the inflammatory mediator
      nitric oxide (NO) and a panel of pro-inflammatory cytokine in LPS-stimulated BV2
      cells, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)
      1alpha, IL-1beta, and IL-6, and also promoted a phenotypic switch from the M1 to
      the M2 phenotype. Additionally, an in vivo study showed that the administration
      of MLB could ameliorate lipopolysaccharide-induced neurodegeneration and
      microglial activation in the hippocampus of adult mice. Mechanistically, MLB
      blocked the activation of the NF-kappaB pathway upon LPS stimulation, indicating
      that the effects of MLB on microglia may be mediated by the NK-kappaB pathway.
      These results suggest the therapeutic potential of MLB as a novel anti
      inflammatory and microglia-modulating drug for neurodegenerative diseases.

PMID- 29196885
TI  - Section 11: Poster Sessions.

PMID- 29196886
TI  - Section I: Oral Sessions.

PMID- 29196887
TI  - The Fourth Annual International Conference on Urban Health, October 26-28, 2005.

PMID- 29196884
TI  - Ultrasonographical Features Associated with Progression of Atherosclerosis in
      Patients with Moderate Internal Carotid Artery Stenosis.
AB  - Carotid artery stenosis (CAS) is a leading cause of ischemic stroke. Plaque
      stabilization is a major management approach. Information about the
      ultrasonographical and clinical features associated with the progression of
      moderate internal carotid artery (ICA) stenosis (50-69%) could assist with
      prognostication and risk factor modifications. We evaluated 287 patients with
      moderate ICA stenosis (50-69%) and subsequently evaluated them at follow-up
      points at 12, 24, and 36 months. Patients were divided into three groups
      according to the degree of ICA stenosis: progression (70-99%, n = 48), stable (50
      69%, n = 210), and regression (< 50%, n = 29). Responsible plaque thickness (RPT)
      across groups during follow-up was compared using a repeated measure ANOVA test.
      An ordinal regression was subsequently applied to identify risk factors for
      atherosclerosis progression. Male (P = 0.04), hypoechoic plaque (P < 0.01),
      smoking (P = 0.02), plaque ulceration (P = 0.05), and contralateral severe CAS or
      occlusions (P = 0.04) on ultrasound was more frequent in the progression group
      vs. other two groups. The ordinal regression revealed that only hypoechoic plaque
      (OR, 7.03; 95% CI, 3.34-14.81; P < 0.01) and contralateral ICA severe stenosis or
      occlusion (OR, 2.86; 95% CI, 1.41-5.80; P < 0.01) were independently associated
      with stenosis progression, while statin use was inversely associated with
      stenosis progression (OR, 0.26; 95% CI, 0.13-0.54; P < 0.01). Of note,
      symptomatic vs. asymptomatic moderate CAS at baseline was not associated with
      progression. For patients with moderate CAS, hypoechoic plaque, contralateral
      severe stenosis or occlusion on ultrasonography, and statin use are independently
      related to stenosis progression. Statin use may delay the progression of carotid
      stenosis.

PMID- 29196888
TI  - Evolving the Urban Health Agenda.

PMID- 29196889
TI  - Durable Resolution of Severe Psoriasis in a Patient Treated with Pentostatin for
      Hairy Cell Leukemia: A Case Report.
AB  - INTRODUCTION: Pentostatin (2'-deoxycoformycin) and cladribine (2
      chlorodeoxyadenosine) are adenosine analogues widely used to treat lymphoid
      malignancies, mainly hairy cell leukemia (HCL). Oral or parenteral adenosine
      analogues have been also used as immunomodulatory agents in multiple sclerosis
      and in acute graft-versus-host disease. CASE REPORT: Here, we report the case of
      a 43-year-old patient with a history of extensive psoriasis who later developed
      HCL. RESULTS: The patient had achieved complete remission of both psoriasis and
      HCL after receiving intravenous infusions of pentostatin. It is worth noting that
      cladribine has already been reported to treat plaque psoriasis lesions in two
      patients with HCL and in a third patient with gastric marginal zone B cell
      lymphoma [1]. CONCLUSION: We believe that adenosine analogues constitute a
      promising therapeutic option for moderate to severe psoriasis, especially for
      severe and refractory psoriasis, as well as for patients with adjacent lymphoid
      malignancies.

PMID- 29196891
TI  - Sodium valproate modulates immune response by alternative activation of monocyte
      derived macrophages in systemic lupus erythematosus.
AB  - The anti-inflammatory role of macrophages in apoptotic cells (ACs) clearance is
      involved in Systemic Lupus Erythematosus (SLE) pathogenesis. The efferocytic
      capability of macrophages is altered by M1/M2 polarization. Histone deacetylase
      inhibitors (HDACi) are proposed to enhance the expansion of M2 macrophages.
      Sodium valproate (VPA) is an HDACi with different anti-inflammatory properties.
      Here, we aimed to investigate the effects of HDACi by VPA on the polarization of
      monocyte-derived macrophages (MDMs) and regulating the expression of anti
      inflammatory cytokines in SLE. We studied the ex vivo alterations of MDMs among
      15 newly diagnosed SLE patients and 10 normal subjects followed by ACs and VPA
      treatments. M1/M2 polarization was assessed by expression of CD86/CD163, IL1
      beta, IDO-1, and MRC-1 among treated and non-treated MDMs. We also evaluated the
      production of IL-10, IL-12, TGF-beta1, and TNF-alpha cytokines in the cell
      culture supernatants. CD163 was overexpressed upon VPA treatment, while CD86
      showed no significant change. IL1-beta and IDO-1 genes were significantly
      downregulated, and the mRNA expression of MRC-1 was increased among VPA-treated
      MDMs of SLE patients. The anti-inflammatory cytokines (IL-10 and TGF-beta1) were
      overproduced while TNF-alpha level was decreased in response to VPA. The
      population of classically activated macrophages was more prevalent among SLE
      patients and efferocytosis was defected. VPA could successfully enhance the anti
      inflammatory immune response through alternative activation of MDMs in SLE
      patients.

PMID- 29196890
TI  - Malnutrition and sarcopenia in a large cohort of patients with systemic
      sclerosis.
AB  - Systemic sclerosis (SSc) is an autoimmune disease which may lead to malnutrition.
      Previous studies have defined it with different criteria. No thorough evaluations
      of sarcopenia in SSc are available. The aim of the present study was to assess
      the prevalence and the potential association of malnutrition and sarcopenia in a
      large cohort of SSc cases. A total of 141 SSc consecutive outpatients were
      enrolled. Body composition was analyzed by densitometry. Malnutrition was defined
      according to recently published ESPEN criteria, whereas sarcopenia was diagnosed
      in patients with reduced skeletal muscle index. Malnutrition was diagnosed in
      9.2% of patients (95% CI, 4.4-14.0%). Malnourished patients had worse
      gastrointestinal symptoms according to UCLA SCTC GIT 2.0 questionnaire (p =
      0.007), lower physical activity (p = 0.028), longer disease duration (p = 0.019),
      worse predicted DLCO/VA and FVC (p = 0.009, respectively), worse disease severity
      according to Medsger severity score (p < 0.001), lower hemoglobin (p = 0.023),
      and fat-free mass (p < 0.001) and were more often sarcopenic (p < 0.001). In
      multivariate analysis, only FVC (p = 0.006) and disease severity (p = 0.003), in
      particular for the lungs (p = 0.013), were confirmed to be worse in malnourished
      patients. Sarcopenia was diagnosed in 29?140 patients (20.7%; 95% CI, 14.0
      27.4%); 11?29 were also malnourished. In multivariate analysis, sarcopenic
      patients had longer disease duration (p = 0.049), worse DLCO/VA (p = 0.002), and
      lung (p = 0.006) and skin (p = 0.014) involvement. In SSc, malnutrition defined
      with ESPEN criteria was found to be lower than previously reported. Sarcopenia
      was found to be somewhat common. Lung involvement was significantly associated
      with nutritional status and may not be explained only by muscle weakness.

PMID- 29196892
TI  - Rates of and methods used at reoperation for recurrence after primary inguinal
      hernia repair with Prolene Hernia System and Lichtenstein.
AB  - INTRODUCTION: Since the introduction of tension-free mesh repair of inguinal
      hernia ad modum Lichtenstein (L), recurrence rates have been reduced to 1-2%. The
      bi-layer mesh Prolene Hernia System (PHS) is an alternative mesh with a
      theoretical potential to further reduce recurrence rates. However, a reoperation
      due to recurrence after PHS might be technically difficult since both the
      anterior and posterior space has been utilized. METHODS: Data on all males 18-75
      years undergoing primary inguinal hernia repair (IHR) with PHS or L between
      January 1999 and October 2010 was collected from the Swedish Hernia Register
      (SHR). Moreover, data was collected for all operations due to recurrence after
      primary IHR with PHS or L between January 1st 1999 and December 31st 2014.
      RESULTS: A total of 1229 primary IHR with PHS and 78,230 with L was identified.
      Rates of reoperation for recurrence after PHS was significantly lower compared to
      L (1.5 vs. 2.7 %), [OR 0.38 (0.20-0.74)]. A medial recurrence was most common in
      both groups. At reoperation, an open anterior mesh repair was used in 74 % after
      PHS and a posterior mesh repair was performed in 58 % after L. Re-operating time
      was shorter, although not statistically significant in the PHS group (47 vs. 58
      min, p = 0.29). Complication rates after surgery due to recurrence did not differ
      between groups. CONCLUSION: The findings from this dataset suggest that
      recurrence rates after primary IHR with PHS might be lower and that reoperation
      due to recurrence after PHS is not more complicated than after L.

PMID- 29196893
TI  - High yield production of four-carbon dicarboxylic acids by metabolically
      engineered Escherichia coli.
AB  - Several metabolic engineered Escherichia coli strains were constructed and
      evaluated for four-carbon dicarboxylic acid production. Fumarase A, fumarase B
      and fumarase C single, double and triple mutants were constructed in a ldhA adhE
      mutant background overexpressing the pyruvate carboxylase from Lactococcus
      lactis. All the mutants produced succinate as the main four-carbon (C4)
      dicarboxylic acid product when glucose was used as carbon source with the
      exception of the fumAC and the triple fumB fumAC deletion strains, where malate
      was the main C4-product with a yield of 0.61-0.67 mol (mole glucose)-1.
      Additionally, a mdh mutant strain and a previously engineered high-succinate
      producing strain (SBS550MG-Cms pHL413-Km) were investigated for aerobic malate
      production from succinate. These strains produced 40.38 mM (5.41 g/L) and 50.34
      mM (6.75 g/L) malate with a molar yield of 0.53 and 0.55 mol (mole succinate)-1,
      respectively. Finally, by exploiting the high-succinate production capability,
      the strain SBS550MG-Cms243 pHL413-Km showed significant malate production in a
      two-stage process from glucose. This strain produced 133 mM (17.83 g/L) malate in
      47 h, with a high yield of 1.3 mol (mole glucose)-1 and productivity of 0.38 g L
      1 h-1.

PMID- 29196894
TI  - Basic Methods for Isolating and Culturing Microalgae.
AB  - In this chapter, I go through the very basic methods for isolating and setting up
      a microalgae culture. Isolation can be done from local algal strains with a
      micropipette and microscope. Determining algal growth is important and can be
      done by counting cells under a microscope or by determining the change in dry
      weight (DW).

PMID- 29196895
TI  - Targeted Proteomics Driven Verification of Biomarker Candidates Associated with
      Breast Cancer Aggressiveness.
AB  - Breast cancer is the most common and molecularly well-characterized malignant
      cancer in women; however, its progression to metastatic cancer remains lethal for
      78% of patients within 5 years of diagnosis. Identifying novel markers in high
      risk patients using quantitative methods is essential to overcome genetic, inter
      tumor, and intra-tumor variability, and to translate novel findings into cancer
      diagnosis and treatment. Using untargeted proteomics, we recently identified 13
      proteins associated with some key factors of breast cancer aggressiveness:
      estrogen receptors, tumor grade, and lymph node status. Here we verified these
      findings in a set of 96 tumors using targeted proteomics based on selected
      reaction monitoring with mTRAQ labeling (mTRAQ-SRM). This study highlights a
      panel of gene products that could contribute to breast cancer aggressiveness and
      metastasis, and can help develop more precise breast cancer treatments.

PMID- 29196896
TI  - Measurement of Fluorescence for Monitoring Algal Growth and Health.
AB  - Measuring fluorescence is a noninvasive, inexpensive, and quick way of
      determining biomass concentration and health of the algae. Fluorescence is
      generally positively correlated with chlorophyll a and can as such be used as a
      proxy for biomass. In addition, the proportion variable fluorescence of maximal
      fluorescence is a measure of photochemical efficiency, which is affected by
      stress in a very early stage and can as such be used as a proxy for algal health.

PMID- 29196897
TI  - Fractionation of Soluble Proteins Using DEAE-Sepharose, SP-Sepharose, and Phenyl
      Sepharose Chromatographies for Proteomics.
AB  - In order to simplify a complex mixture of soluble proteins from tissues, a
      protocol to fractionate samples prior to two-dimensional (2D) gel electrophoresis
      has been developed. These methods involve the use of DEAE-Sepharose, SP
      Sepharose, and phenyl Sepharose chromatographic columns and the fractionation of
      the protein mixtures based on differential anionic, cationic, and hydrophobic
      properties of the proteins, respectively. Fractionation of the soluble proteins
      with DEAE-Sepharose can result in an increase in the number of detectable 2D gel
      spots. These gel spots are amenable to protein identification by using in-gel
      trypsin digestions, matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry, and peptide mass fingerprinting. The DEAE-Sepharose column
      fractionation acts to partition soluble proteins from cell extracts. Similarly, a
      SP-Sepharose column can fractionate soluble proteins and increase the number of
      detectable gel spots. Lastly, fractionation of cell extract with a phenyl
      Sepharose column can also result in an increase in the number of detectable 2D
      gel spots. This chapter describes an easy, inexpensive way to fractionate soluble
      proteins and a way to better profile proteomes.

PMID- 29196898
TI  - Fabrication of curcumin-loaded electrospun nanofiberous polyurethanes with anti
      bacterial activity.
AB  - Two series of polyurethane (PU), based on polycaprolactone (PCL) as soft segments
      with two different molecular weights (2000 and 530 Da), and hexamethylene
      diisocyanate (HDI) and 1,4-butandiol (BDO) as hard segments were synthesized to
      fabricate curcumin-loaded electrospun nanofibrous PCL-based PU substrate.
      Chemical structures of the synthesized PUs were characterized by FTIR and NMR
      spectroscopy techniques. The thermal properties were analyzed by differential
      scanning calorimetry (DSC) and surface hydrophilicity was studied by static
      contact angle and bulk hydrophilicity was evaluated by water uptake test.
      Thereafter, bead-free PU nanofiberous substrate containing curcumin was
      fabricated by electrospinning and morphology of the mats was observed by scanning
      electron microscopy (SEM). Mechanical properties of the electrospun mats in
      comparison with polymeric films were assessed by a universal test machine. The in
      vitro release of curcumin was studied by UV-Vis spectroscopy. The optical density
      of the bacterial solutions was used to evaluate the antibacterial activity of the
      curcumin-loaded nanofibrous mats against Escherichia coli (E-coli ATCC: 25922).
      The results showed that curcumin-loaded PU synthesized by PCL with molecular
      weight of 2000 Da displayed better mechanical properties as well as better
      antibacterial properties in wound dressing application.

PMID- 29196899
TI  - Trends in the Perpetration of Physical Aggression among Norwegian Adolescents
      2007-2015.
AB  - Most research on trends in physical aggression has shown declining levels among
      adolescents during the past two decades. However, few studies have attempted to
      explain such time trends. Based on two representative cross-sectional surveys of
      students in the final year of high school in 2007 (N = 6631; 58.8% girls) and
      2015 (N = 4145; 60.3% girls), this study reports a substantial decline in
      physical aggression among Norwegian adolescents. Moreover, mediation analyses
      show that declining levels in problematic alcohol use and family violence during
      the same period are plausible explanations for some of this reduction. The
      results are discussed in light of contemporary changes in socialization of
      adolescents, and implications for violence prevention are presented.

PMID- 29196900
TI  - Novel poss reinforced chitosan composite membranes for guided bone tissue
      regeneration.
AB  - In this study, novel composites membranes composed of chitosan matrix and
      polyhedral oligomeric silsesquioxanes (POSS) were fabricated by solvent casting
      method. The effect of POSS loading on the mechanical, morphological, chemical,
      thermal and surface properties, and cytocompatibility of composite membranes were
      investigated and observed by tensile test, atomic force microscopy (AFM), Fourier
      transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA),
      protein adsorption assay, air/water contact angle analysis and WST-1
      respectively. Swelling studies were also performed by water absorption capacity
      determination. Results showed that incorporation of Octa-TMA POSS(r) nanofiller
      to the chitosan matrix increased the surface roughness, protein adsorption and
      swelling capacity of membranes. The addition of POSS enhanced significantly the
      ultimate tensile strength and strain at break of the composite membranes up to 3
      wt% POSS loaded samples. An increase of about 76% in tensile strength and of
      strain at break 1.28% was achieved for 3 wt% POSS loaded nanocomposite membranes
      compared with chitosan membranes. The presence of POSS filler into polymer matrix
      increased the plasma protein adsorption on the surface. Maximum protein capacity
      and swelling was obtained for 10 wt% loaded samples. High cell viability results
      were obtained with indirect extraction of chitosan/POSS composites. Besides, cell
      proliferation and ALP activity results showed that POSS incorporation
      significantly increased the ALP activity of Saos-2 cells cultured on chitosan
      membranes. This novel composite membranes with tunable properties could be
      considered as a potential candidate for guided bone regeneration applications.

PMID- 29196901
TI  - An improved solvent-free synthesis of flunixin and 2-(arylamino) nicotinic acid
      derivatives using boric acid as catalyst.
AB  - A simple solvent-free protocol for the preparation of flunixin, a potent non
      narcotic, non-steroidal anti-inflammatory drugs is reported using boric acid as
      catalyst. Its salt, flunixin meglumine are then prepared under reflux in EtOH.
      This sustainable method are then extended for the synthesis of a series of 2
      (arylamino) nicotinic acid derivatives. The present protocol combines non
      hazardous neat conditions with associated benefits like excellent yield,
      straightforward workup, and use of readily available and safe catalyst in the
      absence of any solvent, which are important factors in the pharmaceutical
      industry. The pathway for catalytic activation of 2-chloronicotic acid with boric
      acid was also investigated using Gaussian 03 program package.

PMID- 29196902
TI  - Current Demographics and Roles of Florida Community Health Workers: Implications
      for Future Recruitment and Training.
AB  - The high prevalence of health disparity diseases (e.g., obesity, Type 2 diabetes)
      among underserved populations in the United States suggests the need for
      increased resources to prevent these diseases and to improve health care access
      and quality in underserved communities. Community health workers are valuable
      resources and facilitators of health care access and quality treatment. The
      purpose of the present study is to provide descriptive information about
      community health workers in Florida and to provide recommendations for improved
      training and expansion of community health workers' roles in research and
      intervention. The study participants were 396 adults (85.1% Female, 75.5%
      Community health workers) who completed the 2015 Florida Community Health Workers
      Census. Participants were recruited by the Health Council of South Florida
      through emails and phone calls to members of the Florida Community Health Worker
      Coalition and various organizations. It was found that several groups
      disproportionately affected by health disparities were underrepresented among the
      community health workers who participated in the census and among the communities
      served by these community health workers. Actions are needed to improve and
      increase the recruitment and training of community health workers in Florida.

PMID- 29196903
TI  - Concurrent Use of Prescription Drugs and Herbal Medicinal Products in Older
      Adults: A Systematic Review.
AB  - BACKGROUND: The use of herbal medicinal products (HMPs) is common among older
      adults; however, little is known about concurrent use with prescription drugs, as
      well as potential interactions associated with such combinations. OBJECTIVE: The
      aim of this systematic review was to identify and evaluate the literature on
      concurrent prescription and HMP use among older adults to assess prevalence,
      patterns, potential interactions and factors associated with this use. METHODS:
      Systematic searches were conducted in the MEDLINE, PsycINFO, EMBASE, CINAHL,
      AMED, Web of Science and Cochrane databases from inception to May 2017 for
      studies reporting concurrent use of prescription medicines with HMPs in adults >=
      65 years of age. Quality was assessed using the Joanna Briggs Institute
      checklists. And the Evidence for Policy and Practice Information and Co
      ordinating Centre (EPPI-Centre) three-stage approach to mixed method research was
      used to synthesise data. RESULTS: Twenty-two studies were included. A definition
      of HMPs or what was considered an HMP was frequently missing. Prevalence of
      concurrent use by older adults varied widely between 5.3 and 88.3%. Prescription
      medicines most combined with HMPs were antihypertensive drugs, beta-blockers,
      diuretics, antihyperlipidemic agents, anticoagulants, analgesics, antihistamines,
      antidiabetics, antidepressants and statins. The HMPs most frequently used were
      Ginkgo biloba, garlic, ginseng, St John's wort, Echinacea, saw palmetto, evening
      primrose oil and ginger. Potential risks of bleeding due to the use of Ginkgo
      biloba, garlic or ginseng with aspirin or warfarin was the most reported herb
      drug interaction. Some data suggest being female, and having a lower household
      income and less than a high-school education were associated with concurrent use.
      CONCLUSION: The prevalence of concurrent prescription drugs and HMP use among
      older adults is substantial and potential interactions have been reported.
      Knowledge of the extent and manner in which older adults combine prescription
      drugs will aid healthcare professionals in appropriately identifying and managing
      patients at risk. Systematic Review Registration Number: PROSPERO
      2014:CRD42014009091.

PMID- 29196905
TI  - Oncology Curricula in Postgraduate General Dentistry Programs: a Survey of
      Residency Program Directors.
AB  - Management of patients undergoing treatment for cancer requires a
      multidisciplinary team including general dentistry providers; however, the
      relative knowledge and training of general dentists in the management of this
      patient population are relatively unknown. The purpose of this study was to
      assess the oncology curricula of postgraduate general dentistry training
      programs, from the perspective of the program directors, to better understand the
      opportunities for and/or barriers to dental care for cancer patients. A cross
      sectional survey was sent to the 275 Commission on Dental Accreditation
      accredited programs; 82 program directors responded (response rate, 30%). More
      than 50% of respondents indicated "none" or "little" curricular emphasis on
      cancer biology, bone marrow transplantation, immunotherapy, or prosthetics for
      use during head and/or neck surgery. Conversely, more than 50% of respondents
      indicated "moderate" or "substantial" emphasis on acute oral effects of cancer
      related therapy, long-term oral effects of cancer-related therapy, antiresorptive
      medication pharmacology, radiotherapy techniques and biological effects, and
      osteonecrosis of the jaw. Residents had the most experience with radiotherapy
      patients and the least with bone marrow or transplantation patients. Overall,
      general dentistry program directors were enthusiastic to participate in the
      multidisciplinary team but reported challenges to including oncology curricula in
      residency training programs. Training for general dentistry providers in
      formalized postgraduate residency programs may be variable or limited-as a
      result, communication regarding patient management is critical. Opportunities
      exist to enhance the general dentistry curricula and, thereby, improve access to
      dental care for patients receiving treatment for cancer.

PMID- 29196906
TI  - Perceptions and Attitudes of Cancer Patients and Caregivers Towards Enrollment in
      Clinical Trials in Lebanon.
AB  - The rates of participation in oncology clinical trials (CTs) are relatively lower
      in the Middle East compared to other areas in the world. Many social and cultural
      factors underlie the patients' reluctance to participate. To probe the knowledge,
      attitudes, and perceptions of patients with cancer and their caregivers regarding
      participation in CTs at our tertiary referral center in Lebanon, we interviewed
      210 patients and caregivers visiting the outpatient clinics in the Naef Basile
      Cancer Institute at the American University of Beirut. A questionnaire was
      derived from literature and administered in Arabic. The study was approved by the
      Institutional Review Board (IRB). Two hundred individuals agreed to answer the
      questionnaire. The majority of participants (90.5%) were Lebanese with the
      remaining being non-Lebanese Arabs. Eighty-nine participants (45%) were aware of
      the concepts of CTs. Eighty-two respondents (41%) would participate in phase I
      CTs. Twenty-nine individuals (14.5%) agree to be enrolled in CTs with the
      approval of their family members only. One hundred twenty-nine subjects (64.5%)
      stated that they would refuse enrollment in a CT where they might receive
      placebo. Eighty-eight (44%) of participants considered that medical records could
      be reviewed for research without consent while 54% agreed that samples collected
      during clinical workup could be used for research without the consent of the
      patient. There are several social and demographic correlates for participation in
      CTs. Raising awareness and overcoming barriers of misconception are keys to
      promote participation in CTs in Lebanon.

PMID- 29196904
TI  - Deletion of psbQ' gene in Cyanidioschyzon merolae reveals the function of
      extrinsic PsbQ' in PSII.
AB  - KEY MESSAGE: We have successfully produced single-cell colonies of C. merolae
      mutants, lacking the PsbQ' subunit in its PSII complex by application of DTA
      aided mutant selection. We have investigated the physiological changes in PSII
      function and structure and proposed a tentative explanation of the function of
      PsbQ' subunit in the PSII complex. We have improved the selectivity of the
      Cyanidioschyzon merolae nuclear transformation method by the introduction of
      diphtheria toxin genes into the transformation vector as an auxiliary selectable
      marker. The revised method allowed us to obtained single-cell colonies of C.
      merolae, lacking the gene of the PsbQ' extrinsic protein. The efficiency of gene
      replacement was extraordinarily high, allowing for a complete deletion of the
      gene of interest, without undesirable illegitimate integration events. We have
      confirmed the absence of PsbQ' protein at genetic and protein level. We have
      characterized the physiology of mutant cells and isolated PSII protein complex
      and concluded that PsbQ' is involved in nuclear regulation of PSII activity, by
      influencing several parameters of PSII function. Among these: oxygen evolving
      activity, partial dissociation of PsbV, regulation of dimerization, downsizing of
      phycobilisomes rods and regulation of zeaxanthin abundance. The adaptation of
      cellular physiology appeared to favorite upregulation of PSII and concurrent
      downregulation of PSI, resulting in an imbalance of energy distribution, decrease
      of photosynthesis and inhibition of cell proliferation.

PMID- 29196907
TI  - Fluorescence Investigations on Interactions between 7,8-benzo-4-azidomethyl
      Coumarin and Ortho- and Para-phenylenediamines in Binary Solvent Mixtures of THF
      and Water.
AB  - Fluorescence investigations on interactions between 7,8-benzo-4-azidomethyl
      coumarin (7BAMC) and quenchers ortho-phenylenediamine (OPD) and para
      phenylenediamines (PPD) in binary solvent mixtures (THF + water) have been
      reported. UV-absorption study indicated a weak hydrophobic interaction between
      7BAMC and the para isomer. NMR spectral studies indicated the presence of an
      interaction between 7BAMC and PPD. Magnitudes of the parameters associated with
      FRET, showed the presence of interactions between 7BAMC and PPD quencher is more
      predominant than OPD. Fluorescence quenching studies reveal the role of static
      and dynamic quenching pathways, depending upon Stern-Volmer constant, dielectric
      constant and dominant non-radiative processes. Binding equilibria analysis
      indicates a strong interaction between 7BAMC and PPD than OPD and formation of H
      bonding. Based on the magnitudes of free energy, enthalpy change and entropy,
      bimolecular interaction process may be considered as spontaneous and hydrophobic.

PMID- 29196908
TI  - Do chimpanzees anticipate an object's weight? A field experiment on the
      kinematics of hammer-lifting movements in the nut-cracking Tai chimpanzees.
AB  - When humans are about to manipulate an object, our brains use visual cues to
      recall an internal representation to predict its weight and scale the lifting
      force accordingly. Such a long-term force profile, formed through repeated
      experiences with similar objects, has been proposed to improve manipulative
      performance. Skillful object manipulation is crucial for many animals,
      particularly those that rely on tools for foraging. However, despite enduring
      interest in tool use in non-human animals, there has been very little
      investigation of their ability to form an expectation about an object's weight.
      In this study, we tested whether wild chimpanzees use long-term force profiles to
      anticipate the weight of a nut-cracking hammer from its size. To this end, we
      conducted a field experiment presenting chimpanzees with natural wooden hammers
      and artificially hollowed, lighter hammers of the same size and external
      appearance. We used calibrated videos from camera traps to extract kinematic
      parameters of lifting movements. We found that, when lacking previous experience,
      chimpanzees lifted hollowed hammers with a higher acceleration than natural
      hammers (overshoot effect). After using a hammer to crack open one nut,
      chimpanzees tuned down the lifting acceleration for the hollowed hammers, but
      continued lifting natural hammers with the same acceleration. Our results show
      that chimpanzees anticipate the weight of an object using long-term force
      profiles and suggest that, similarly to humans, they use internal representations
      of weight to plan their lifting movements.

PMID- 29196909
TI  - Rhesus monkeys (Macaca mulatta) remember agency information from past events and
      integrate this knowledge with spatial and temporal features in working memory.
AB  - The purpose of the present study was to examine whether rhesus monkeys remember
      information about their own agency-along with spatial, temporal and contextual
      properties-from a previously experienced event. In Experiment 1, rhesus monkeys
      (n = 4) used symbols to reliably indicate whether they had performed or observed
      an event on a computer screen. In Experiment 2, naive and experienced monkeys (n
      = 8) reported agency information when stringent controls for perceptual and
      proprioceptive cues were included. In Experiment 3, five of the monkeys completed
      a task in which they reported agency information along with spatial and temporal
      features of events. Two monkeys performed this agency discrimination when they
      could not anticipate which memory test they would receive. There was also
      evidence that these features were integrated in memory. Implications of this
      research are discussed in relation to working memory, episodic memory and self
      awareness in nonhuman animals.

PMID- 29196911
TI  - Proceedings from the 2017 Journal of Nuclear Cardiology board meeting.

PMID- 29196912
TI  - What is this image? 2017: Image 4 result : Improvement of ischemia with statin
      therapy.

PMID- 29196910
TI  - Radiopharmaceutical tracers for cardiac imaging.
AB  - Cardiovascular disease (CVD) is the leading cause of death and disease burden
      worldwide. Nuclear myocardial perfusion imaging with either single-photon
      emission computed tomography or positron emission tomography has been used
      extensively to perform diagnosis, monitor therapies, and predict cardiovascular
      events. Several radiopharmaceutical tracers have recently been developed to
      evaluate CVD by targeting myocardial perfusion, metabolism, innervation, and
      inflammation. This article reviews old and newer used in nuclear cardiac imaging.

PMID- 29196913
TI  - UBAP2L silencing inhibits cell proliferation and G2/M phase transition in breast
      cancer.
AB  - BACKGROUND: Ubiquitin-associated protein 2-like (UBAP2L) contains a ubiquitin
      associated domain near its N-terminus, which has been demonstrated to be
      overexpressed in multiple tumors, including hepatocellular carcinoma and
      colorectal carcinoma but its role has not been well studied in breast cancer.
      Thus, this study was designed to evaluate whether UBAP2L can serve as a potential
      molecular target for breast cancer therapy. METHODS: The expression of UBAP2L was
      determined in breast cancer tissues and cell lines by Western blotting and
      Oncomine database mining. Then the expression of UBAP2L was silenced using RNA
      interference and the effects of UBAP2L knockdown on breast cancer cell
      proliferation and cell cycle progression by MTT and colony formation assay, and
      Flow cytometry, respectively. RESULTS: We found the expression of UBAP2L was
      significantly up-regulated in breast cancer tissues and cell lines. Knockdown of
      UBAP2L suppressed cell proliferation, impaired colony formation ability and
      induced cell cycle arrest at G2/M phase. At molecular levels, knockdown of UBAP2L
      increased p21 expression, but decreased the expression of CDK1 and Cyclin B1 in
      breast cancer cells. CONCLUSION: Our findings suggest that UBAP2L plays an
      important role in breast cancer cell proliferation and might serve as a potential
      target for breast cancer treatment.

PMID- 29196914
TI  - Health care utilisation amongst older adults with sensory and cognitive
      impairments in Europe.
AB  - Worldwide, the high prevalence of multiple chronic conditions amongst older
      population has led to increased utilisation of health care and rising associated
      costs, becoming a major public health concern. Hearing, vision and cognitive
      disorders are common chronic conditions amongst older Europeans and recent
      studies have documented its high co-occurrence. While it has been shown
      separately that suffering either mental disorders or sensory (hearing and vision)
      impairments is associated with higher health care utilisation, the association
      between health care utilisation and the interaction of these conditions has
      received little attention in the literature. Therefore, using four waves of the
      Survey of Health, Ageing and Retirement in Europe (SHARE), this study applies the
      correlated random effects method to the negative binomial and finite mixture
      models to analyse the extent to which the interaction of cognitive and sensory
      impairments is associated with health care use. We found that individuals with
      cognitive impairment tend to have more hospitalisations. The finite mixture
      approach indicates a positive association between sensory impairment and the
      number of hospitalisations amongst low users of health care. Additionally, our
      findings suggest a positive association between suffering both impairments at the
      same time and the number of doctor and GP visits.

PMID- 29196915
TI  - Coexistence of left ventricular hypertrophy and noncompaction: a case report.

PMID- 29196916
TI  - Bullying Victimization Heightens Cortisol Response to Psychosocial Stress in
      Chinese Children.
AB  - Childhood adverse experiences have been consistently documented to engender
      persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis reactivity to
      chronic stress. However, there has been very little research examining whether
      this effect can be elicited among children when using a standardized laboratory
      stress test, or whether such effects are found in non-Western youth. In the
      current study, 80 10-year-old Chinese children (45% girls, 4-5th grades) were
      selected from 970 students based on the experience of being bullied, resulting in
      a sample of 59 victims (physical, verbal, and relational/social), and a group of
      21 nonbullied children with distributions of age and gender that were comparable.
      We examined the association between bullying victimization and cortisol
      reactivity to the Trier Social Stress Test (TSST) at six time points using
      repeated-measures analyses of variance. The results showed that the TSST was a
      valid protocol among Chinese children for testing the functioning of HPA axis,
      based on two indicators: cortisol increase in response to stressor, and cortisol
      decrease after stressor removal. Based on the TSST, both cortisol reactivity and
      total cortisol concentration over the course of TSST were higher in bullied
      children relative to nonbullied children. Moreover, there were no differences in
      cortisol levels between victimization sub-types. Our study extended prior
      findings, by showing that cortisol dysregulation in response to stress may be
      related to bullying victimization.

PMID- 29196917
TI  - Development of a linear dual column HPLC-MS/MS method and clinical genetic
      evaluation for tramadol and its phase I and II metabolites in oral fluid.
AB  - Tramadol is a centrally acting synthetic opioid analgesic and has received
      special attention due to its abuse potential and unexpected responses induced by
      CYP2D6 polymorphism. Oral fluid is an advantageous biofluid for drug analysis due
      to non-invasive sampling and high correlation of drug concentrations with plasma.
      However, few studies have been performed on distribution of tramadol and its
      metabolites in oral fluid. In the present study, a linear dual column HPLC-MS/MS
      method was developed and fully validated for the simultaneous determination of
      tramadol and its phase I [O-desmethyltramadol (ODMT), N-desmethyltramadol (NDMT)
      and N,O-didesmethyltramadol (NODMT)] and II metabolites in oral fluid.
      Furthermore, the distribution of tramadol and its metabolites, in relation to
      CYP2D6 genetic variations, in oral fluid was investigated following a clinical
      study including 23 subjects with CYP2D6*wt/*wt, CYP2D6*10/*10 or CYP2D6*5/*5. The
      validation results of selectivity, matrix effect, linearity, precision and
      accuracy were satisfactory. Pharmacokinetic parameters, such as Css,max and AUC0
      tau of tramadol, NDMT and NODMT, in the CYP2D6*10/*10 group were significantly
      higher than those in the CYP2D6*wt/*wt group. Moreover, the ratios of
      ODMT/tramadol, NDMT/tramadol and NODMT/NDMT correlated well with the CYP2D6
      genotypes. We demonstrated that oral fluid is a promising biofluid for
      pharmacokinetic evaluation in relation to genetic variations.

PMID- 29196918
TI  - Nafamostat mesilate negatively regulates the metastasis of triple-negative breast
      cancer cells.
AB  - Triple-negative breast cancer (TNBC) lacking of oestrogen receptor, progesterone
      receptor, and epidermal growth factor receptor type 2 is a highly malignant
      disease which results in a poor prognosis and rare treatment options. Despite the
      use of conventional chemotherapy for TNBC tumours, resistance and short duration
      responses limit the treatment efficacy. Therefore, a need exists to develop a new
      chemotherapy for TNBC. The aim of this study was to examine the anti-cancer
      effects of nafamostat mesilate (NM), a previously known serine protease inhibitor
      and highly safe drug on breast cancer cells. Here, we showed that NM
      significantly inhibits proliferation, migration, and invasion in MDA-MB231 cells,
      induces G2/M phase cell-cycle arrest, and inhibits the expression of cyclin
      dependent kinase 1 (CDK1). Exposure of MDA-MB231 cells to NM also resulted in
      decreased transcription factor activities accompanied by the regulated
      phosphorylation of signalling molecules and a decrease in metalloproteinases, the
      principal modulators of the extracellular environment during cancer progression.
      Especially, inhibition of TGFbeta-stimulated Smad2 phosphorylation and subsequent
      metastasis-related gene expression, and downregulation of ERK activity may be
      pivotal mechanisms underlying inhibitory effects of NM on NM inhibits lung
      metastasis of breast cancer cells and growth of colonized tumours in mice. Taken
      together, our data revealed that NM inhibits cell growth and metastasis of TNBC
      cells and indicated that NM is a multi-targeted drug that could be an adjunct
      therapy for TNBC treatment.

PMID- 29196919
TI  - The Combined Efficiency of Dietary Isomaltooligosaccharides and Bacillus spp. on
      the Growth, Hemato-Serological, and Intestinal Microbiota Indices of Caspian
      Brown Trout (Salmo trutta caspius Kessler, 1877).
AB  - The combined effects of a commercial probiotic, BetaPlus(r), and a prebiotic,
      isomaltooligosaccharides (IMOS) on the growth, survival rate, intestinal
      microbiota, and hemato-immunological parameters were evaluated in Caspian brown
      trout (Salmo trutta caspius Kessler, 1877). Caspian brown trout fingerlings (~ 9
      g) were fed a control diet (basal diet) or a synbiotic diet (the basal diet + 2 g
      kg-1 IMOS + 1 g kg-1 BetaPlus(r)) for 7 weeks. At the end of this trial, fish fed
      the synbiotic diet showed significant improvements in body weight increase, feed
      conversion ratio, and survival rate compared with fish fed the control diet (P <
      0.05). In addition, fish fed the synbiotic diet had the highest levels of white
      blood cells, monocytes, and neutrophils (P < 0.05), while the red blood cells,
      hemoglobin, hematrocrit, mean corpuscular volume, and lymphocytes were
      significantly higher in the control group (P < 0.05). The serum triglycerides,
      cholesterol, total protein, albumin, albumin/globulin ratio, and immunoglobulin M
      levels, as well as alanine aminotransferase and lactate dehydrogenase activities
      were higher in the synbiotic group than in the control group (P < 0.05). In
      addition, fish fed the synbiotic diet showed significantly higher gut total
      viable aerobic bacterial counts and lactic acid bacteria (P < 0.05). The results
      demonstrated that BetaPlus(r) in combination with IMOS enhanced the growth,
      survival rate, intestinal microbiota, and some haemato-immunological parameters
      in Caspian brown trout fingerlings.

PMID- 29196920
TI  - Probiotic Bacillus coagulans GBI-30, 6086 Improves Protein Absorption and
      Utilization.
AB  - Probiotics offer numerous health benefits, including digestive and immune health.
      Improved digestive health is linked to a more efficient absorption of important
      nutrients from our diet. This review focused on the rationale of using the
      probiotic Bacillus coagulans GBI-30, 6086 to aid protein absorption and
      utilization. B. coagulans GBI-30, 6086 can withstand the acidic environment of
      the stomach to reach the intestine where it germinates. Once active in the small
      intestine after germination, it has been shown to aid the digestion of
      carbohydrates and proteins. Co-administration of B. coagulans GBI-30, 6086 with
      protein has been shown to increase protein absorption and to maximize the health
      benefits associated with protein supplementation.

PMID- 29196921
TI  - Viability and Stress Response of Putative Probiotic Lactobacillus plantarum
      Strains in Honey Environment.
AB  - Due to problem of preservation of dairy products which serve as a matrix for
      probiotics, it is challenging to use these probiotics as food supplements in many
      developing countries. To determine the suitability of the Lactobacillus strains
      for exploitation as probiotics in honey, we investigated the effect of their
      storage on the viability, functionality, and the mechanism associated with their
      protective effect. Three isolates obtained from our laboratory collection were
      identified through amplification of the 16S rRNA gene. The viability of the
      strains in honey at different storage conditions was studied. Three genes (hdc,
      gtf, and clpL) responsible for the resistance of bacteria in acidic environments
      were screened. SDS-PAGE analysis of total protein was performed to observe
      protein profile changes of the strains after exposure to honey. All the three
      isolates, namely, GGU, GLA51, and GLP56, were identified as Lactobacillus
      plantarum strains. After 28 days of storage in honey at 4  degrees C, viable cell
      concentrations of the three strains were higher than 2.04 * 106 CFU/ml. During
      the same period at room temperature, only the Lactobacillus plantarum GLP56
      strain remained viable with a cell concentration of 1.86 * 104 CFU/ml. The clpL
      gene coding for ATPase was detected in all the three strains. The protein of
      molecular weight ~ 50 kDa was absent in the protein profile of Lactobacillus
      plantarum GGU after 60 days of storage in honey at 4  degrees C. The
      Lactobacillus plantarum GLP56, Lactobacillus plantarum GLA51, and Lactobacillus
      plantarum GGU strains exposed to honey can withstand acidic environmental stress
      but their viability declines over time.

PMID- 29196922
TI  - Nosocomial Candiduria in the Elderly: Microbiological Diagnosis.
AB  - Candiduria is associated with high morbidity, mortality, and long
      hospitalization, involving high costs for the healthcare system. The use of
      increasingly aggressive treatments has prolonged the lives of patients
      susceptible to candiduria, namely the immunosuppressed, the premature, and the
      elderly. Our objective was to evaluate the incidence of nosocomial candiduria and
      the implicated species in hospitalized patients aged over 80 years old from three
      Spanish centers during 2012 and 2013. Urine samples received from these patients
      were cultured and analyzed by flow cytometry in search of leukocyturia,
      hematuria, proteinuria, and microbial nitrate reductase activity. The isolated
      yeast species were identified microscopically, by germ tube formation in serum,
      colony morphology after subculture onto CHROMagar Candida (Becton-Dickinson, UK),
      assimilation of carbon compounds ID32C (bioMerieux, France), matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDITOF) (Bruker
      Daltonics, Germany) and, in case of inconsistency, by sequencing of the ITS
      regions of ribosomal DNA (ITS1-5, 8S-ITS2). Susceptibility tests were also
      performed. The incidence of candiduria in the elderly population was 10.3%. A
      total of 155 strains of yeasts were isolated. The predominant species was Candida
      albicans, followed by Candida glabrata and then Candida tropicalis. Several
      infrequent species were found; among them, the first isolate of candiduria
      producing Candida pulcherrima described in the literature. Our finding should
      raise concerns about the elderly population, which is probably the most important
      risk group for candiduria in the present moment, and the emergence of unusual
      yeast species producing candiduria, which are resistant against the commonly used
      antifungal agents.

PMID- 29196923
TI  - Mixed Infection of Respiratory Tract in a Dog Caused by Rhodotorula mucilaginosa
      and Trichosporon jirovecii: A Case Report.
AB  - This report describes the isolation of two environmental fungi: Rhodotorula
      mucilaginosa and Trichosporon jirovecii accompanied by Pseudomonas aeruginosa and
      Escherichia coli from a dog with bronchotracheitis. All microorganisms were
      isolated routinely from a mucopurulent discharge, obtained during bronchoscopy
      from laryngotracheal area. The initial identification of yeasts was confirmed by
      API Candida and by molecular analysis of internal transcribed spacer region.
      Administered antimicrobial treatment with Marbofloxacin and Canizol has brought
      the improvement in the dogs' health status. The final results of control
      mycological culture were negative. Most probably underlying hypothyroidism and
      the use of steroids were the factors predisposing this patient to opportunistic
      infection of mixed aetiology. As far as we are concerned, this is the first case
      of dogs' respiratory tract infection caused by R. mucilaginosa and T. jirovecii.

PMID- 29196924
TI  - Cutaneotrichosporon (Trichosporon) debeurmannianum: A Rare Yeast Isolated from
      Blood and Urine Samples.
AB  - Cutaneotrichosporon (Trichosporon) debeurmannianum is a rarely isolated yeast
      from clinical samples. Nine isolates of this yeast were identified from clinical
      samples within a period of 3 years from June 2012 to May 2015. These isolates
      were from blood and urine samples sent to a clinical mycology laboratory of a
      tertiary care hospital in Assam, North East India. Clinically, the patients were
      diagnosed as septicemia and urinary tract infection. The age of the patients
      ranged from 2 to 50 years. Identification was made by sequencing the ITS region
      of ribosomal RNA gene. Antifungal susceptibility test by disk diffusion method
      (CLSI, M44-A) showed all the isolates to be sensitive to fluconazole and
      voriconazole. Vitek 2 compact commercial yeast identification system
      misidentified this yeast as Cryptococcus laurentii and low discrimination
      Cryptococcus laurentii/Trichosporon mucoides. This species was originally named
      as Trichosporon debeurmannianum. In 2015, this yeast has been included into new
      genera Cutaneotrichosporon based on an integrated phylogenetic classification of
      the Tremellomycetes. To the best of our knowledge, this is the first report of
      identification of this species from blood and urine samples of clinically
      suspected cases. We are reporting these isolates because of their rarity in
      clinical samples. The pathogenic potential and epidemiological relevance of this
      yeast remains to be seen.

PMID- 29196925
TI  - Pre-operative language ability in patients with presumed low-grade glioma.
AB  - In patients with low-grade glioma (LGG), language deficits are usually only found
      and investigated after surgery. Deficits may be present before surgery but to
      date, studies have yielded varying results regarding the extent of this problem
      and in what language domains deficits may occur. This study therefore aims to
      explore the language ability of patients who have recently received a presumptive
      diagnosis of low-grade glioma, and also to see whether they reported any changes
      in their language ability before receiving treatment. Twenty-three patients were
      tested using a comprehensive test battery that consisted of standard aphasia
      tests and tests of lexical retrieval and high-level language functions. The
      patients were also asked whether they had noticed any change in their use of
      language or ability to communicate. The test scores were compared to a matched
      reference group and to clinical norms. The presumed LGG group performed
      significantly worse than the reference group on two tests of lexical retrieval.
      Since five patients after surgery were discovered to have a high-grade glioma, a
      separate analysis excluding them were performed. These analyses revealed
      comparable results; however one test of word fluency was no longer significant.
      Individually, the majority exhibited normal or nearly normal language ability and
      only a few reported subjective changes in language or ability to communicate.
      This study shows that patients who have been diagnosed with LGG generally show
      mild or no language deficits on either objective or subjective assessment.

PMID- 29196926
TI  - Glioblastoma and acute myeloid leukemia: malignancies with striking similarities.
AB  - Acute myeloid leukemia (AML) and glioblastoma (GB) are two malignancies
      associated with high incidence of treatment refractoriness and generally,
      uniformly poor survival outcomes. While the former is a hematologic (i.e. a
      "liquid") malignancy and the latter a solid tumor, the two diseases share both
      clinical and biochemical characteristics. Both diseases exist predominantly in
      primary (de novo) forms, with only a small subset of each progressing from
      precursor disease states like the myelodysplastic syndromes or diffuse glioma.
      More importantly, the primary and secondary forms of each disease are
      characterized by common sets of mutations and gene expression abnormalities. The
      primary versions of AML and GB are characterized by aberrant RAS pathway, matrix
      metalloproteinase 9, and Bcl-2 expression, and their secondary counterparts share
      abnormalities in TP53, isocitrate dehydrogenase, ATRX, inhibitor of apoptosis
      proteins, and survivin that both influence the course of the diseases themselves
      and their progression from precursor disease. An understanding of these shared
      features is important, as it can be used to guide both the research about and
      treatment of each.

PMID- 29196927
TI  - Characteristics of cerebellar glioblastomas in adults.
AB  - Adult cerebellar glioblastomas (cGBM) are rare and their characteristics remain
      to be fully described. We analyzed the characteristics of 17 adult patients with
      cGBM and compared them to a series of 103 patients presenting a supra-tentorial
      glioblastoma (stGBM). The mean age at GBMc diagnosis was 53.4 years (range 28
      77). A history of neurofibromatosis type I was noted in 3 patients. cGBM were
      hemispheric in 10 patients (58.8%), only vermian in 4 patients (23.5%), and both
      vermian and hemispheric in 3 patients (17.7%). A H3 K27M mutation was identified
      in 3/14 patients, a TERT promoter mutation in 3/14 patients and a methylated MGMT
      promoter in 3/14 patients. None of the patients (0/14) harbored an EGFR
      amplification, an IDH or a BRAF mutation. Association with neurofibromatosis type
      I and H3K27M mutations were mutually exclusive. Compared with stGBM, cGBM
      occurred in younger patients (53.4 vs. 63.2, p = 0.02), were more frequently
      associated with neurofibromatosis type I (18 vs. 1%, p = 0.009) and with a H3
      K27M mutation (21 vs. 3%, p = 0.02). They also tended to have a more frequent
      multifocal presentation at diagnosis (21 vs. 4.3%, p = 0.06), more frequently
      resulted in leptomeningeal or intra-axial metastasis (44.5 vs. 5%, p = 0.002) and
      were associated with a shorter median overall survival (5.9 vs. 14.2 months, p =
      0.004). The present study suggests that adult cGBM differ from their supra
      tentorial counterpart and constitute a heterogeneous group of IDH wild-type
      gliomas with at least two subgroups, one associated with H3K27M mutations and the
      other with neurofibromatosis type I.

PMID- 29196928
TI  - The effect of L-thyroxine substitution on oxidative stress in early-stage
      diabetic nephropathy patients with subclinical hypothyroidism: a randomized
      double-blind and placebo-controlled study.
AB  - PURPOSE: To study oxidative stress status of early type 2 diabetic nephropathy
      (DN) patients with subclinical hypothyroidism (SCH) and to assess effect of L
      thyroxine therapy on the oxidative stress in these patients. METHODS: It is a
      randomized double-blind and placebo-controlled trial. A total of 48 patients with
      early type 2 DN were included as Euthyroid group, and 92 early type 2 DN with SCH
      were selected and randomly assigned to L-thyroxine treatment group (LT4 group)
      and placebo group (SCH group). Changes in urinary albumin excretion rate (UAER),
      serum malondialdehyde (MDA), superoxide dismutase (SOD) activity, urine 8
      hydroxyl deoxyguanosine (8-OHdG), serum creatinine, estimated glomerular
      filtration rate, and lipid profile before and after 24 weeks of follow-up were
      examined and compared. RESULTS: The levels of UAER, MDA, 8-OHdG were higher,
      while the SOD activity was lower in DN patients with SCH than in DN patients (p <
      0.05 for all). In the LT4 group, the levels of UAER, MDA, 8-OHdG decreased
      significantly (p < 0.05) to levels no longer different from the Euthyroid group.
      The SOD activity increased significantly. But in SCH group, the levels of mAlb,
      MDA, 8-OHdG were greater after 24 weeks of follow-up and greater than patients in
      the Euthyroid group. SOD activity decreased significantly after 24 weeks in the
      SCH group (p < 0.05). CONCLUSION: Oxidative stress is greater in the DN patients
      with SCH, and SCH may exacerbate kidney injury in early DN patients. The LT4
      treatment may decrease the oxidative stress and attenuate renal injury in DN
      patient with SCH.

PMID- 29196929
TI  - Factors associated with calcium requirements after parathyroidectomy in chronic
      kidney disease patients.
AB  - BACKGROUND: Renal hyperparathyroidism is a common complication of chronic kidney
      disease (CKD). Parathyroidectomy (PTX) for these patients continues to be a
      valuable option in the era of calcimimetics. Postoperative hypocalcemia is common
      after surgery. The aim of this study was to identify clinical factors to define
      postoperative calcium requirements. METHODS: From February 2013 to May 2017, 68
      patients with chronic kidney disease 5 (CKD5) who underwent PTX were reviewed. We
      collected clinical and laboratory data preoperatively and calculated the total
      calcium requirement in a week after surgery. Univariate and multiple analyses
      were performed to study whether these clinical and laboratory factors were
      associated with calcium requirement. RESULTS: Univariate analysis showed that
      preoperative alkaline phosphatase (ALP), calcium (Ca), parathyroid hormone and
      hemoglobin were independently associated with calcium requirement. Multivariate
      model showed that the preoperative ALP was the only independent factor that could
      predict the requirement of calcium. CONCLUSIONS: In the context of a high dCa
      (1.75 mmol/l) and a stable dose of calcitriol, preoperative ALP levels were
      significantly associated with calcium requirement in patients with CKD5
      undergoing PTX.

PMID- 29196930
TI  - Association of ALOX12 gene polymorphism with all-cause and cardiovascular
      mortality in diabetic nephropathy.
AB  - PURPOSE: Cardiovascular (CV) events are the first cause of death in patients with
      chronic renal disease (CKD) and in patients with type 2 diabetes mellitus (DM2).
      The combination of CKD and DM2 elevates the risk of both cardiovascular disease
      (CVD) and death in this high-risk population. Besides traditional risk factors,
      such as dyslipidemia, smoking, obesity, and carotid atherosclerosis, novel
      factors are under investigation such as genetic polymorphisms. Lipoxygenases
      (LOXs) and their genes are of critical importance in oxidative stress,
      inflammation, and atherosclerosis. The aim of the study is to clarify a potential
      ALOX12 role in CVD presence and progress of diabetic patients in different stages
      of nephropathy. METHODS: We studied 145 patients with a documented history of DM2
      for at least 10 years and diabetic nephropathy (DN), mean age 68 +/- 9 years,
      body mass index 31 +/- 5 kg/m2, and different stages of renal disease, depending
      on glomerular filtration rate. The sample population consisted of two groups: 108
      DM2 patients with DN in all five stages of CKD and 37 DM2 patients as controls.
      Anthropometric and clinical characteristics, interview for history of previous CV
      event, and assessment of carotid intima-media thickness (cIMT) were recorded at
      baseline. All patients were genotyped for ALOX12 polymorphisms with focus on
      rs14309. Genotypes (AA, AG, and GG) were evaluated for any possible role in CVD,
      and grouping was performed on A genotype, which is the dominant model. All
      participants were followed over a period of 7 years, and the end points studied
      were all-cause mortality, CV mortality, and CV events. CV events were defined as
      myocardial infarction (MI), stroke, or peripheral artery disease. RESULTS: The GG
      genotype has been significantly associated with cIMT levels above 0.86 mm and
      with history of MI. Regarding the presence of an atherosclerotic plaque in either
      carotid artery, no significant association was found when the genotypes were
      assessed on their own. After grouping, though, GG genotype revealed a significant
      association between carotid plaque formation and atheromatosis. Kaplan-Meier
      analysis revealed that ALOX12 gene GG genotype predicted all-cause mortality, CV
      mortality, and CV events. Similarly, when AA and AG genotypes were grouped,
      Kaplan-Meier analysis showed that patients with GG genotype presented an even
      more significant higher all-cause mortality, CV mortality, and CV events compared
      with AA and AG genotypes combined. After adjustment for several traditional risk
      factors, multivariate Cox proportional hazard analysis showed that patients with
      the GG genotype had a significant higher risk of all-cause mortality, a threefold
      increase in CV mortality, and a twofold increased risk for CV events compared to
      patients with the AA or the AG genotype. CONCLUSION: ALOX12 rs14309 GG genotype
      expression was found to be significantly associated with MI, higher cIMT,
      increased CV events, CV, and overall mortality. This phenomenon could be
      partially explained by the increased platelet proaggregatory activity of AA
      products and the control they exert in thrombotic occurrence and plaque
      formation.

PMID- 29196931
TI  - Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious
      Effect on Bone in Growing Obese Rats.
AB  - Metabolic syndrome and osteoporosis share similar risk factors. Also, patients
      with diabetes have a higher risk of osteoporosis and fracture. Liver
      manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic
      syndrome are further aggravated in diabetics and often lead to liver failure. Our
      objective was to create a rat model of human metabolic syndrome and determine the
      long-term impact of early-onset T1D on bone structure and strength in obese
      growing rats. Male rats were given either standard chow and RO water (Controls)
      or a high-fat, high-cholesterol diet and sugar water containing 55% fructose and
      45% glucose (HFD). A third group of rats received the HFD diet and a single dose
      of streptozotocin to induce type 1 diabetes (HFD/Sz). Body weight and glucose
      tolerance tests were conducted several times during the course of the study.
      Serum chemistry, liver enzymes, and biomarkers of bone metabolism were evaluated
      at 10 and 28 weeks. Shear wave elastography and histology were used to assess
      liver fibrosis. Cancellous bone structure and cortical bone geometry were
      evaluated by mCT and strength by the 3-point bending method. Body mass and fat
      accumulation was significantly higher in HFD and HFD/Sz rats compared to
      Controls. Rats in both the HFD and HFD/Sz groups developed NASH, although the
      change was more severe in diabetic rats. Although both groups of obese rats had
      larger bones, their cancellous structure and cortical thickness were reduced,
      resulting in diminished strength that was further aggravated by diabetes. The HFD
      and HFD/Sz rats recapitulate MeSy in humans with liver pathology consistent with
      NASH. Our data provide strong indication that obesity accompanied by type 1
      diabetes significantly aggravates comorbidities of MeSy, including the
      development of osteopenia and weaker bones. The juvenile rat skeleton seems to be
      more vulnerable to damage imposed by obesity and diabetes and may offer a model
      to inform the underlying pathology associated with the unusually high fracture
      rates in obese adults with diabetes.

PMID- 29196932
TI  - Efficient Bioconversion of High Concentration Phytosterol Microdispersion to 4
      Androstene-3,17-Dione (AD) by Mycobacterium sp. B3805.
AB  - Low solubility of sterols in aqueous media limits efficient steroid production
      mediated by biocatalytic microorganisms such as Mycobacterium. Sterol emulsion
      technologies have been developed with low success rates, largely due to the
      complexity of generating stable and bioavailable particles. In this study,
      several aqueous dispersions of sterols in-water of different particle sizes were
      bioconverted to 4-androstene-3,17-dione (AD) in a solvent-free environment, using
      a classic microorganism Mycobacterium sp. B3805 as a model system. According to
      our results, the high concentration (20 g/L) phytosterol dispersions with the
      smallest particle size tested (370 nm) achieved up to 54% (7.4 g/L) AD production
      yield in 11 days. Moreover, the use of 0.1 biomass/sterols ratio in a complex
      bioconversion media containing yeast extract, and a 1:1 glucose/microdispersion
      ratio in the presence of the surfactant DK-Ester P-160 (HLB16), allowed
      homogenization and increased microdispersion stability, thus achieving the best
      results using emulsion technologies to date.

PMID- 29196933
TI  - Osmolyte Type and the Osmolarity Level Affect Chondrogenesis of Mesenchymal Stem
      Cells.
AB  - The inductive effects of increased osmolarity on chondrogenesis are well
      approved. However, the effects of the osmolyte agent invoked to induce
      hyperosmolarity are largely neglected. Herein, we scrutinized how hyperosmotic
      conditions acquired by addition of different osmolytes would impact
      chondrogenesis. We briefly assessed whether such conditions would differentially
      affect hypertrophy and angiogenesis during MSC chondrogenesis. Chondrogenic and
      hypertrophic marker expression along with VEGF secretion during adipose-derived
      (AD)-MSC chondrogenesis under three osmolarity levels (350, 450, and 550 mOsm)
      using three different osmolytes (NaCl, sorbitol, and PEG) were assessed. MTT
      assay, qRT-PCR, immunocytochemistry, Alcian Blue staining, ELISA, and ALP assays
      proved osmolyte-type dependent effects of hyperosmolarity on chondrogenesis,
      hypertrophy, and angiogenesis. At same osmolarity level, PEG had least
      cytotoxic/cytostatic effect and most prohibitive effects on angiogenesis. As
      expected, all hyperosmolar conditions led to enhanced chondrogenesis with
      slightly varying degrees. PEG and sorbitol had higher chondro-promotive and
      hypertrophy-suppressive effects compared to NaCl, while NaCl had exacerbated
      hypertrophy. We observed that TonEBP was involved in osmoadaptation of all
      treatments in varying degrees. Of importance, we highlighted differential effects
      of hyperosmolarity obtained by different osmolytes on the efficacy of
      chondrogenesis and more remarkably on the induction/suppression of cartilage
      pathologic markers. Our study underlies the need for a more vigilant exploitation
      of physicobiochemical inducers in order to maximize chondrogenesis while
      restraining unwanted hypertrophy and angiogenesis.

PMID- 29196934
TI  - Allogeneic Transplant for Mycosis Fungoides in Patient with Wiskott-Aldrich
      Syndrome.

PMID- 29196936
TI  - Eye taping and chlorhexidine exposure: caution when interpreting scarce evidence.

PMID- 29196935
TI  - Serial femtosecond crystallography at the SACLA: breakthrough to dynamic
      structural biology.
AB  - X-ray crystallography visualizes the world at the atomic level. It has been used
      as the most powerful technique for observing the three-dimensional structures of
      biological macromolecules and has pioneered structural biology. To determine a
      crystal structure with high resolution, it was traditionally required to prepare
      large crystals (> 200 MUm). Later, synchrotron radiation facilities, such as
      SPring-8, that produce powerful X-rays were built. They enabled users to obtain
      good quality X-ray diffraction images even with smaller crystals (ca. 200-50
      MUm). In recent years, one of the most important technological innovations in
      structural biology has been the development of X-ray free electron lasers
      (XFELs). The SPring-8 Angstrom Compact free electron LAser (SACLA) in Japan
      generates the XFEL beam by accelerating electrons to relativistic speeds and
      directing them through in-vacuum, short-period undulators. Since user operation
      started in 2012, we have been involved in the development of serial femtosecond
      crystallography (SFX) measurement systems using XFEL at the SACLA. The SACLA
      generates X-rays a billion times brighter than SPring-8. The extremely bright
      XFEL pulses enable data collection with microcrystals (ca. 50-1 MUm). Although
      many molecular analysis techniques exist, SFX is the only technique that can
      visualize radiation-damage-free structures of biological macromolecules at room
      temperature in atomic resolution and fast time resolution. Here, we review the
      achievements of the SACLA-SFX Project in the past 5 years. In particular, we
      focus on: (1) the measurement system for SFX; (2) experimental phasing by SFX;
      (3) enzyme chemistry based on damage-free room-temperature structures; and (4)
      molecular movie taken by time-resolved SFX.

PMID- 29196937
TI  - Neurogenic dysphagia with undigested macaroni and megaesophagus in familial
      dysautonomia.

PMID- 29196938
TI  - The hemodynamic and pain impact of peripheral nerve block versus spinal
      anesthesia in diabetic patients undergoing diabetic foot surgery.
AB  - PURPOSE: Comparison of hemodynamic profiles and pain scores in diabetic patients
      undergoing diabetic foot surgery receiving peripheral nerve block (PNB) or spinal
      anesthesia [subarachnoid block (SAB)]. METHODS: This was a prospective,
      randomised controlled trial. We recruited diabetic patients aged > 18 years,
      American Society of Anesthesiologists class II-III, who were scheduled for
      unilateral diabetic foot surgery below the knee. All patients were assessed for
      autonomic dysfunction using the Survey of Autonomic Symptoms score. Participants
      were randomly assigned to receive either PNB or SAB for the surgery. Hemodynamic
      data, including usage of vasopressors, were recorded at 5-min intervals for up to
      1 h after the induction of anesthesia. Pain scores were recorded postoperatively,
      and follow-up was done via telephone 6 months later. RESULTS: Compared to the PNB
      group, the SAB group had a larger number of patients with significant hypotension
      (14 vs. 1; p = 0.001) and more patients who required vasopressor boluses (6 vs. 0
      patients). Compared to SAB group, the patients in the PNB group had a longer
      postoperative pain-free duration (9 vs. 4.54 h; p = 0.002) and lower pain scores
      1 day after surgery (3.63 vs. 4.69; p = 0.01). CONCLUSION: Peripheral nerve block
      should be considered, whenever possible, as the first option of anesthesia for
      lower limb surgery in diabetic patients as it provides hemodynamic stability and
      superior postoperative pain control compared to SAB. TRIAL REGISTRATION: Clinical
      trial registry: ClinicalTrials.gov. ID NCT02727348.

PMID- 29196941
TI  - Gastric Calcifying Fibrous Tumor Manifesting as a Subepithelial Tumor.
AB  - A gastric subepithelial tumor is a common finding during upper gastric endoscopy.
      The differential diagnosis of such lesions is broad, and sometimes a rare disease
      can be diagnosed. A calcifying fibrous tumor (CFT) is a rare, benign mesenchymal
      tumor that usually affects children and young adults. To our knowledge, a CFT of
      the tubular gastrointestinal tract is very rare with fewer than 30 cases of
      gastric CFTs reported in the literature.

PMID- 29196939
TI  - Clinical and functional implication of the components of somatostatin system in
      gastroenteropancreatic neuroendocrine tumors.
AB  - PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a
      heterogeneous group of malignancies often presenting with metastasis at diagnosis
      and whose clinical outcome is difficult to predict. Somatostatin (SST) analogs
      (SSAs) provide a valuable pharmacological tool to palliate hormonal symptoms, and
      control progression in some NETs. However, many patients do not respond to SSAs
      or develop resistance, and there are many uncertainties regarding pathophysiology
      of SST and its receptors (sst1-sst5) in GEP-NETs. METHODS: The expression of SST
      system components in GEP-NETs was determined, compared with that of non-tumor
      adjacent and normal tissues and correlated with clinical and histological
      characteristics. Specifically, 58 patients with GEP-NETs and 14 normal samples
      were included. Cell viability in NET cell lines was determined in response to
      specific SSAs. RESULTS: Normal samples and non-tumor adjacent tissues presented a
      similar expression profile, with appreciable expression of sst2 and sst3, and a
      lower expression of the other receptors. In contrast, cortistatin, sst1, sst4,
      and sst5 were overexpressed in tumors, while sst3 and sst4 seemed overexpressed
      in less differentiated tumors. Some SST system components were related to
      vascular/nerve invasion and metastasis. In vitro, sst1 and sst3 agonists reduced
      viability in BON-1 cells, while they, similar to octreotide and pasireotide,
      increased viability in QGP-1 cells. CONCLUSIONS: These results provide novel
      information on SST system pathophysiology in GEP-NETs, including relevant
      associations with clinical-histological parameters, which might help to better
      understand the intrinsic heterogeneity of NETs and to identify novel biomarkers
      and/or targets with potential prognostic and/or therapeutic value for GEP-NETs
      patients.

PMID- 29196940
TI  - Evolution of intron-poor clades and expression patterns of the
      glycosyltransferase family 47.
AB  - MAIN CONCLUSION: A large-scale bioinformatics analysis revealed the origin and
      evolution of GT47 gene family, and identified two clades of intron-poor genes
      with putative functions in drought stress responses and seed development in
      maize. Glycosyltransferase family 47 (GT47) genes encode beta
      galactosyltransferases and beta-glucuronyltransferases that synthesize pectin,
      xyloglucans and xylan, which are important components of the plant cell wall. In
      this study, we performed a systematic and large-scale bioinformatics analysis of
      GT47 gene family using 352 GT47 proteins from 15 species ranging from
      cyanobacteria to seed plants. The analysis results showed that GT47 family may
      originate in cyanobacteria and expand along the evolutionary trajectory to moss.
      Further analysis of 47 GT47 genes in maize revealed that they can divide into
      five clades with diverse exon-intron structures. Among these five clades, two
      were mainly composed with intron-poor genes, which may originate in the moss.
      Gene duplication analysis revealed that the expansion of GT47 gene family in
      maize was significantly driven from tandem duplication events and segmental
      duplication events. Significantly, almost all duplicated genes are intron-poor
      genes. Expression analysis indicated that several intron-poor GT47 genes may be
      involved in the drought stress response and seed development in maize. This work
      provides insight into the origin and evolutionary process, expansion mechanisms
      and expression patterns of GT47 genes, thus facilitating their functional
      investigations in the future.

PMID- 29196942
TI  - Spinal movement and dural sac compression during airway management in a cadaveric
      model with atlanto-occipital instability.
AB  - PURPOSE: To analyze the compression of the dural sac and the cervical spinal
      movement during performing different airway interventions in case of atlanto
      occipital dislocation. METHODS: In six fresh cadavers, atlanto-occipital
      dislocation was performed by distracting the opened atlanto-occipital joint
      capsule and sectioning the tectorial membrane. Airway management was done using
      three airway devices (direct laryngoscopy, video laryngoscopy, and insertion of a
      laryngeal tube). The change of dural sac's width and intervertebral angulation in
      stable and unstable atlanto-occipital conditions were recorded by video
      fluoroscopy with myelography. Three-dimensional overall movement of cervical
      spine was measured in a wireless human motion track system. RESULTS: Compared
      with a mean dural sac compression of - 0.5 mm (- 0.7 to - 0.3 mm) in stable
      condition, direct laryngoscopy caused an increased dural sac compression of - 1.6
      mm (- 1.9 to - 0.6 mm, p = 0.028) in the unstable atlanto-occipital condition. No
      increased compression on dural sac was found using video laryngoscopy or the
      laryngeal tube. Moreover, direct laryngoscopy caused greater overall extension
      and rotation of cervical spine than laryngeal tube insertion in both stable and
      unstable conditions. Among three procedures, the insertion of a laryngeal tube
      took the shortest time. CONCLUSION: In case of atlanto-occipital dislocation,
      intubation using direct laryngoscopy exacerbates dural sac compression and may
      cause damage to the spinal cord.

PMID- 29196943
TI  - Letter to the Editor concerning ''Efficacy and safety of tranexamic acid in
      reducing blood loss in scoliosis surgery: a systematic review and meta
      analysis.'' by Yuan, QM. et al. (Eur Spine J; 2017. doi:10.1007/s00586-016-4899
      0).

PMID- 29196944
TI  - Scientometric evaluation of the global research in spine: an update on the
      pioneering study by Wei et al.
AB  - PURPOSE: Wei et al. evaluated the global research in spine using scientometric
      methods based on a sample of 13,115 papers published in 5 spine journals from
      2004 to 2013. This study builds on this pioneering study and provides up-to-date
      and thorough information on spine based on a sample of 166,962 papers for the
      stakeholders. METHOD: 'Articles' and 'reviews' published in 'English' in the
      journals indexed by the 'Web of Science' primary databases between 1980 and 2017
      were retrieved through the use of an optimal keyword set for titles of both
      papers and ten spine journals. The information on document types and number of
      papers, authors, countries, funding bodies, institutions, publication years,
      journals, 'Web of Science' subject categories, and ten top citation classics were
      analyzed. RESULTS: A large sample of 166,962 papers were retrieved. The 'reviews'
      and 'proceedings papers' formed 5.8 and 2.8% of the sample, respectively.
      'Fehlings', 'Vaccaro', 'Takahashi', 'Lenke', and 'Gokaslan' were the most
      prolific authors. Nearly 0.7% of the papers had group authors besides single
      authors. The US was the most prolific country publishing 37.3% of the sample
      whilst Europe contributed to more than 39.8% of the sample. Only, 26.6% of the
      papers disclosed research funding. Among 40,897 institutions, 'Harvard
      University' was the most-prolific institution whilst the US institutions
      dominated the top-institution list. The research output steadily rose from 1375
      papers in 1980 to 9357 papers in 2016 whilst 69.2% of the papers were published
      after 2000. Ten spine journals published only 23.4% of the sample. 'Clinical
      Neurology', 'Orthopedics', 'Neurosciences', and 'Surgery' was the most prolific
      subject categories. The top citation classic was a paper by van der Linden et al.
      on ankylosing spondylitis. CONCLUSIONS: The optimal design of research sample
      made it possible to obtain nearly 13 times the size of the sample in Wei et al.
      as a true representation of the research in spine through the use of an optimal
      keyword set for the titles of both papers and 10 spine journals. However, despite
      the inefficient design of the incentive structures for the relevant stakeholders,
      the research in spine had expanded 6.8 times since 1980.

PMID- 29196945
TI  - Pain in Platin-Induced Neuropathies: A Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN
      in cancer patients. The aim of this paper is to systematically review the current
      literature regarding PIPN, with a particular focus on epidemiological and
      clinical characteristics of painful PIPN, and to discuss relevant management
      strategies. METHODS: A systematic computer-based literature search was conducted
      on the PubMed database. RESULTS: This search strategy resulted in the
      identification of 353 articles. After the eligibility assessment, 282 articles
      were excluded. An additional 24 papers were identified by scanning the reference
      lists. In total, 95 papers met the inclusion criteria and were used for this
      review. The prevalence of neuropathic symptoms due to acute toxicity of
      oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy
      with platins was estimated at 74.9%. Specifically regarding pain, the reported
      prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%,
      whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN
      was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common
      complication in patients receiving platins and can be particularly painful. There
      is significant heterogeneity among studies regarding the method for diagnosing
      peripheral neuropathy. Nerve conduction studies are the gold standard and should
      be performed in patients receiving platins and complaining of neuropathic
      symptoms post-treatment.

PMID- 29196947
TI  - Effect of bleaching agent extracts on murine macrophages.
AB  - OBJECTIVES: The aim of this study was to evaluate the cytotoxicity and the
      influence of bleaching agents on immunologically cell surface antigens of murine
      macrophages in vitro. MATERIALS AND METHODS: RAW 264.7 cells were exposed to
      bleaching gel extracts (40% hydrogen peroxide or 20% carbamide peroxide) and
      different H2O2 concentrations after 1 and 24-h exposure periods and 1-h exposure
      and 23-h recovery. Tests were performed with and without N-acetyl cysteine (NAC)
      and buthionine sulfoximine (BSO). Cell viability was determined by MTT assay. The
      expression of surface markers CD14, CD40, and CD54 with and without LPS
      stimulation was detected by flow cytometry, while the production of TNF-alpha was
      measured by ELISA. Statistical analysis was performed using the Mann-Whitney U
      test (alpha = 0.05). RESULTS: Extracts of bleaching agents were cytotoxic for
      cells after a 1-h exposure; cells could not recover after 24 h. This effect can
      be mitigated by the antioxidant NAC and increased by BSO, an inhibitor of
      glutathione (GSH) synthesis. LPS stimulated expression of all surface markers and
      TNF-alpha production. Exposure to bleaching agent extracts and H2O2 leads to a
      reduction of TNF-alpha, CD14, and CD40 expression, while the expression of CD54
      was upregulated at non-cytotoxic concentrations. Whereas NAC reduced this effect,
      it was increased in the presence of BSO. CONCLUSIONS: Extracts of bleaching
      agents were irreversibly cytotoxic to macrophages after a 1-h exposure. Only the
      expression of CD54 was upregulated. The reactions are mediated by the non
      enzymatic antioxidant GSH. CLINICAL RELEVANCE: The addition of an antioxidant can
      downregulate unfavorable effects of dental bleaching.

PMID- 29196948
TI  - Fracture behavior of all-ceramic, implant-supported, and tooth-implant-supported
      fixed dental prostheses.
AB  - OBJECTIVES: In vitro investigation of the effects of fixed dental prosthesis
      (FDP) support and loading conditions on the fracture behavior of all-ceramic,
      zirconia-based FDP veneered with computer-aided design/computer-aided
      manufacturing (CAD/CAM)-manufactured lithium disilicate ceramic. MATERIALS AND
      METHODS: Based on a model for a 3-unit FDP in the molar region (tooth in region
      15, implant in region 17), 16 identical zirconia frameworks were fabricated and
      veneered with milled lithium disilicate ceramic. Another 16 FDPs were
      manufactured similarly, using a model in which the tooth was replaced by an
      implant. The specimens underwent 10,000 thermal cycles between 6.5 and 60 
      degrees C and 1,200,000 chewing cycles with a force magnitude of 100 N. All were
      then subsequently loaded until fracture in a universal testing device. Half of
      the FDPs were subjected to centric and axial loading on the pontic, the others to
      eccentric and oblique loading on one cusp of the pontic. RESULTS: No failures
      were observed after artificial aging. Fracture loads of tooth-implant-supported
      restorations were 1636 +/- 158 and 1086 +/- 156 N for axial and oblique loading,
      respectively; implant-supported FDPs fractured at 1789 +/- 202 and 1200 +/- 68 N,
      respectively. Differences were significant for load application (P < 0.001) and
      support type (P = 0.020). For the two types of load application, fracture mode
      differed substantially: complete fracture was observed for centric and axial
      loading whereas mixed cohesive/adhesive failure was observed for many FDPs loaded
      eccentrically and obliquely. CONCLUSIONS: The high incidence of chipping of
      manually veneered implant-supported all-ceramics restorations might be reduced by
      use of CAD/CAM-manufactured lithium disilicate veneers. CLINICAL RELEVANCE: FDPs
      veneered with lithium disilicate resist occlusal forces of 500 N, irrespective of
      load application and support type. The fracture resistance of implant-supported
      FDPs was, however, higher than that of combined tooth-implant-supported FDPs.
      Their clinical use seems to be justified.

PMID- 29196949
TI  - Accuracy and eligibility of CBCT to digitize dental plaster casts.
AB  - OBJECTIVES: Software-based dental planning requires digital casts and oftentimes
      cone-beam computed tomography (CBCT) radiography. However, buying a dedicated
      model digitizing device can be expensive and might not be required. The present
      study aimed to assess whether digital models derived from CBCT and models
      digitized using a dedicated optical device are of comparable accuracy. MATERIAL
      AND METHODS: A total of 20 plaster casts were digitized with eight CBCT and five
      optical model digitizers. Corresponding models were superimposed using six
      control points and subsequent iterative closest point matching. Median distances
      were calculated among all registered models. Data were pooled per scanner and
      model. Boxplots were generated, and the paired t test, a Friedman test, and a
      post-hoc Nemenyi test were employed for statistical comparison. Results were
      found significant at p < 0.05. RESULTS: All CBCT devices allowed the digitization
      of plaster casts, but failed to reach the accuracy of the dedicated model
      digitizers (p < 0.001). Median distances between CBCT and optically digitized
      casts were 0.064 + - 0.005 mm. Qualitative differences among the CBCT systems
      were detected (chi 2 = 78.07, p < 0.001), and one CBCT providing a special
      plaster cast digitization mode was found superior to the competitors (p < 0.05).
      CONCLUSION: CBCT systems failed to reach the accuracy from optical digitizers,
      but within the limits of the study, accuracy appeared to be sufficient for
      digital planning and forensic purposes. CLINICAL RELEVANCE: Most CBCT systems
      enabled digitization of plaster casts, and accuracy was found sufficient for
      digital planning and storage purposes.

PMID- 29196950
TI  - Transcriptome analysis of Pseudomonas sp. from subarctic tundra soil: pathway
      description and gene discovery for humic acids degradation.
AB  - Although humic acids (HA) are involved in many biological processes in soils and
      thus their ecological importance has received much attention, the degradative
      pathways and corresponding catalytic genes underlying the HA degradation by
      bacteria remain unclear. To unveil those uncertainties, we analyzed
      transcriptomes extracted from Pseudomonas sp. PAMC 26793 cells time-dependently
      induced in the presence of HA in a lab flask. Out of 6288 genes, 299 (microarray)
      and 585 (RNA-seq) were up-regulated by > 2.0-fold in HA-induced cells, compared
      with controls. A significant portion (9.7% in microarray and 24.1% in RNA-seq) of
      these genes are predicted to function in the transport and metabolism of small
      molecule compounds, which could result from microbial HA degradation. To further
      identify lignin (a surrogate for HA)-degradative genes, 6288 protein sequences
      were analyzed against carbohydrate-active enzyme database and a self-curated list
      of putative lignin degradative genes. Out of 19 genes predicted to function in
      lignin degradation, several genes encoding laccase, dye-decolorizing peroxidase,
      vanillate O-demethylase oxygenase and reductase, and biphenyl 2,3-dioxygenase
      were up-regulated > 2.0-fold in RNA-seq. This induction was further confirmed by
      qRT-PCR, validating the likely involvement of these genes in the degradation of
      HA.

PMID- 29196951
TI  - Behavioral and Biochemical Effects of N-Acetylcysteine in Zebrafish Acutely
      Exposed to Ethanol.
AB  - Alcohol hangover refers to unpleasant symptoms experienced as a direct
      consequence of a binge drinking episode. The effects observed in this condition
      are related to the increase in alcohol metabolites and imbalance in oxidative
      status. N-acetylcysteine (NAC) is a mucolytic agent and an antidote for
      paracetamol overdose. Preclinical and clinical studies have shown that NAC is a
      multi-target drug acting through neuroprotective, antioxidant and neurotrophic
      mechanisms as well as a glutamate modulator. The aim of this study was to
      investigate the effects of NAC in zebrafish acutely exposed to ethanol (EtOH).
      Animals pretreated or not with NAC (1 mg/L, 10 min) were exposed for 60 min to
      standard tank water (EtOH-) or to 1% EtOH (EtOH+) to evaluate anxiety-like
      behavior and locomotion in the novel tank test and oxidative damage in the brain.
      Zebrafish (Danio rerio) exposed to EtOH displayed a decrease in the distance
      traveled, crossings, entries and time spent in the top area in the novel tank
      test. Exposure to EtOH also caused oxidative damage, shown by increased lipid
      peroxidation, decreased non-protein thiols and increased production of reactive
      oxygen species (DCF assay). NAC prevented both the behavioral alterations and the
      oxidative stress observed in EtOH+ animals. Given the effects of NAC in
      preventing the acute behavioral and biochemical effects of EtOH, additional
      studies are warranted to further investigate the basis of its anecdotal use to
      prevent hangover.

PMID- 29196952
TI  - Fabrication and Characterization of Electrospun Bi-Hybrid PU/PET Scaffolds for
      Small-Diameter Vascular Grafts Applications.
AB  - In spite of advances have been made during the past decades, the problems
      associated with small-diameter vascular grafts, including low patency and
      compliance mismatch and in consequence of that thrombosis, aneurysm and intimal
      hyperplasia are still challenges. To address these problems, net polyurethane
      (PU) and poly (ethylene terephthalate) (PET) polymers and hybrid PU/PET were
      electrospun to create three different types of small-diameter vascular scaffolds
      due to their unique physicochemical characteristics: PU, PET, and novel hybrid
      PU/PET scaffolds. The results show that the PU and PET composite can improve the
      mechanical properties of the tissue-engineered vascular scaffolds in the range of
      the native vessels where the non-cytotoxicity characteristic of these well-known
      polymers is still immutable. The compliance and stiffness factor of the
      fabricated hybrid scaffolds were 4.468 +/- 0.177 and 22.718 +/- 0.896%/0.01 mmHg,
      respectively, which were significantly different with that of the net PU and PET
      electrospun scaffolds. Other properties such as ultimate tensile stress (UTS)
      (3.56 +/- 1.21 MPa) were also in good accordance with the native vessels.
      Furthermore, FT-IR analysis testified the presence of both PU and PET in the
      hybrid scaffolds. Overall, we were able to fabricate a hybrid scaffold as a small
      diameter vascular graft that mechanically matched the gold standard of blood
      vessel substitution.

PMID- 29196954
TI  - Prevalence of Human Parainfluenza Viruses and Noroviruses Genomes on Office
      Fomites.
AB  - The aim of this study was to evaluate the potential role of office fomites in
      respiratory (human parainfluenza virus 1-HPIV1, human parainfluenza virus 3
      HPIV3) and enteric (norovirus GI-NoV GI, norovirus GII-NoV GII) viruses
      transmission by assessing the occurrence of these viruses on surfaces in office
      buildings. Between 2016 and 2017, a total of 130 surfaces from open-space and non
      open-space rooms in office buildings located in one city were evaluated for
      HPIV1, HPIV3, NoV GI, and NoV GII viral RNA presence. Detection of viruses was
      performed by RT-qPCR method. Study revealed 27 positive samples, among them 59.3%
      were HPIV3-positive, 25.9% HPIV1-positive, and 14.8% NoV GII-positive. All tested
      surfaces were NoV GI-negative. Statistical analysis of obtained data showed that
      the surfaces of office equipment including computer keyboards and mice,
      telephones, and desktops were significantly more contaminated with respiratory
      viruses than the surfaces of building equipment elements such as door handles,
      light switches, or ventilation tracts (chi 2 p = 0.006; Fisher's Exact p =
      0.004). All examined surfaces were significantly more contaminated with HPIVs
      than NoVs (chi 2 p = 0.002; Fisher's Exact p = 0.003). Office fomites in open
      space rooms were more often contaminated with HPIVs than with NoVs (chi 2 p =
      0.016; Fisher's Exact p = 0.013). The highest average concentration of HPIVs RNA
      copies was observed on telephones (1.66 * 102 copies/100 cm2), while NoVs on the
      light switches (1.40 * 102 copies/100 cm2). However, the Kruskal-Wallis test did
      not show statistically significant differences in concentration levels of viral
      RNA copies on surfaces between the all tested samples. This study unequivocally
      showed that individuals in office environment may have contact with both
      respiratory and enteric viral particles present on frequently touched surfaces.

PMID- 29196955
TI  - Simple linear brainstem MRI measurements in the differential diagnosis of
      progressive supranuclear palsy from the parkinsonian variant of multiple system
      atrophy.
AB  - Differential diagnosis of progressive supranuclear palsy (PSP) and the
      parkinsonian variant of multiple system atrophy (MSA-P) from Parkinson's disease
      (PD) can be difficult, particularly in atypical cases or early in the disease
      course. The Magnetic Resonance Parkinsonism Index (MRPI) utilizes linear and
      surface (planimetry) measurements and has been proposed as a dual MRI biomarker,
      with high values indicative of PSP and low values of MSA. The aim of this study
      was to examine the utility of simple linear MRI brainstem measurements, without
      the use of MRI planimetry, in the diagnosis of patients with Parkinsonism and
      compare them to the MRPI. A total of 51 patients (PSP: 24, MSA-P: 9, PD: 18) and
      15 healthy controls were included. Simple linear MRI distances of brainstem
      structures were measured. These included midbrain and pons diameters as well as
      superior cerebellar peduncle (SCP) and middle cerebellar peduncle (MCP) widths.
      All relevant indices, including ratios and products, were also calculated. The
      SCP by midbrain product (SCP * midbrain) provided improved sensitivity (100 vs.
      91%) and identical specificity (98%) for the diagnosis of PSP, compared to the
      MRPI. Neither the MRPI nor any of the linear measurements were able to
      discriminate MSA-P from PD. The SCP by midbrain product is a novel, potent MRI
      biomarker for PSP.

PMID- 29196953
TI  - Preservative-Free Prostaglandin Analogs and Prostaglandin/Timolol Fixed
      Combinations in the Treatment of Glaucoma: Efficacy, Safety and Potential
      Advantages.
AB  - Glaucoma therapy-related ocular surface disease (OSD) is a serious pathology with
      a broad spectrum of insidious clinical presentations and complex pathogenesis
      that undermines long-term glaucoma care. Preservatives, especially benzalkonium
      chloride (BAK), contained in topical intraocular pressure-lowering medications
      frequently cause or aggravate OSD in glaucoma. Management of these patients is
      challenging, and to date often empirical due to the scarcity of controlled long
      term clinical trials. Most of the available data are extracted from case series
      and retrospective analysis. Preservative-free prostaglandins and
      prostaglandin/timolol fixed combinations are novel options developed to remove
      the harmful impact of preservatives, especially BAK, upon ocular tissues. Based
      on what is currently known on the value of preservative-free antiglaucoma
      therapies it is tempting to speculate how these new therapies may affect the
      future medical management of all glaucoma patients. This article provides a
      comprehensive and critical review of the current literature on preservative-free
      prostaglandins and preservative-free prostaglandin/timolol fixed combinations.

PMID- 29196956
TI  - ASPP2 Inhibits the Profibrotic Effects of Transforming Growth Factor-beta1 in
      Hepatic Stellate Cells by Reducing Autophagy.
AB  - BACKGROUND: Apoptosis-stimulating protein of p53-2 (ASPP2) is a damage-inducible
      P53-binding protein that enhances damage-induced apoptosis. Fibrosis is a wound
      healing response, and hepatic stellate cells (HSCs) are key players in liver
      fibrogenesis. However, little is known about the relationship between ASPP2 and
      hepatic fibrosis. AIMS: We investigated the effects of ASPP2 overexpression in
      HSCs and the role of ASPP2 in mouse liver fibrogenesis. METHODS: Human HSCs (LX-2
      cells) were pre-incubated with GFP adenovirus (Ad) or ASPP2 adenovirus (AdASPP2)
      for 24 h and then treated with or without TGF-beta1. ASPP2+/- and ASPP2+/+ Balb/c
      mice were used to examine the effects of ASPP2 on liver fibrosis in vivo.
      ASPP2+/+ Balb/c mice were generated by injecting AdASPP2 into the tail vein of
      ASPP2 WT Balb/c mice; all mice received intraperitoneal injections of carbon
      tetrachloride. RESULTS: In this study, ASPP2 was found to markedly inhibit TGF
      beta1-induced fibrogenic activation of LX-2 cells. Further experiments using an
      autophagic flux assay confirmed that ASPP2 reduced the fibrogenic activation of
      LX-2 cells by inhibiting autophagy. Moreover, we found that ASPP2 overexpression
      attenuated the anti-apoptotic effects of TGF-beta1 in LX-2 cells. The extent of
      liver fibrosis was markedly reduced in ASPP2+/+ mouse liver tissue compared with
      control mice; however, in ASPP2+/- mice, hepatic collagen deposition was
      significantly increased. CONCLUSION: These results suggest that TGF-beta1-induced
      autophagy is required for the fibrogenic response in LX-2 cells and that ASPP2
      may both inhibit TGF-beta1-induced autophagy and decrease liver fibrosis.

PMID- 29196957
TI  - Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients
      with advanced cancer.
AB  - Background The signaling protein p38 mitogen-activated protein kinase (MAPK)
      regulates the tumor cell microenvironment, modulating cell survival, migration,
      and invasion. This phase 1 study evaluated the safety of p38 MAPK inhibitor
      LY3007113 in patients with advanced cancer to establish a recommended phase 2
      dose. Methods In part A (dose escalation), LY3007113 was administered orally
      every 12 h (Q12H) at doses ranging from 20 mg to 200 mg daily on a 28-day cycle
      until the maximum tolerated dose (MTD) was reached. In part B (dose
      confirmation), patients received MTD. Safety, pharmacokinetics, pharmacodynamics,
      and tumor response data were evaluated. Results MTD was 30 mg Q12H. The most
      frequent treatment-related adverse events (>10%) were tremor, rash, stomatitis,
      increased blood creatine phosphokinase, and fatigue. Grade >= 3 treatment-related
      adverse events included upper gastrointestinal haemorrhage and increased hepatic
      enzyme, both occurring at 40 mg Q12H and considered dose-limiting toxicities.
      LY3007113 exhibited an approximately dose-proportional increase in exposure and
      time-independent pharmacokinetics after repeated dosing. Maximal inhibition (80%)
      of primary biomarker MAPK-activated protein kinase 2 in peripheral blood
      mononuclear cells was not reached, and sustained minimal inhibition (60%) was not
      maintained for 6 h after dosing to achieve a biologically effective dose (BED).
      The best overall response in part B was stable disease in 3 of 27 patients.
      Conclusions The recommended phase 2 dosage of LY3007113 was 30 mg Q12H. Three
      patients continued treatment after the first radiographic assessment, and the BED
      was not achieved. Further clinical development of this compound is not planned as
      toxicity precluded achieving a biologically effective dose.

PMID- 29196958
TI  - Surgical management of complicated rectovaginal fistulas and the role of
      omentoplasty.
AB  - BACKGROUND: Patients with rectovaginal fistulas have a significantly reduced
      quality of life. Therefore, surgical therapy is often needed even in palliative
      cases. The aim of the present study was to perform an analysis of the results of
      the different treatment options available today. METHODS: We performed a
      retrospective analysis of patients who underwent treatment for rectovaginal
      fistulas at the Department of Surgery, University of Schleswig-Holstein, Campus
      Luebeck and the Department of Surgery, WKK Heide, between January 2000 and
      September 2016. Complication and recurrence rate were retrospectively evaluated.
      The median follow-up period was 13 months (range 3-36 months). RESULTS: During
      the observation period, 58 patients underwent surgery (53 curative, 5 palliative)
      for rectovaginal fistulas. All patients who underwent curative surgery had an
      omentoplasty, and 39 of 53 (73.6%) patients underwent a resection. Thirty of 39
      (77.0%) resections were low anterior resection, while non-continence-preserving
      resection included subtotal colectomy (n = 5), pelvic exenteration (n = 2), and
      proctectomy (n = 2). The fistulas were mainly secondary to inflammatory bowel
      disease (n = 18) or diverticulitis (n = 13), while 19 fistulas were a
      complication of different cancers or precancerous lesions. The median follow-up
      time was 13 months (range 6-36). Four patients (6.9%) had fistula recurrence (3
      recurrences after low anterior resection, 1 after primary fistula closure). The
      mortality rate was 6.9% (n = 4). CONCLUSIONS: Non-resecting methods should be
      used only in uncomplicated fistulas. Rectovaginal fistulas secondary to
      inflammatory or malignant disease mostly require extensive therapy. Omentoplasty
      is effective for the treatment of both high and low rectovaginal fistulas.

PMID- 29196959
TI  - Right colic artery anatomy: a systematic review of cadaveric studies.
AB  - BACKGROUND: Complete mesocolic excision for right-sided colon cancer may offer an
      oncologically superior excision compared to traditional right hemicolectomy
      through high vascular tie and adherence to embryonic planes during dissection,
      supported by preoperative scanning to accurately define the tumour lymphovascular
      supply and drainage. The authors support and recommend precision oncosurgery
      based on these principles, with an emphasis on the importance of understanding
      the vascular anatomy. However, the anatomical variability of the right colic
      artery (RCA) has resulted in significant discord in the literature regarding its
      precise arrangement. METHODS: We systematically reviewed the literature on the
      incidence of the different origins of the RCA in cadaveric studies. An electronic
      search was conducted as per Preferred Reporting Items for Systematic Reviews and
      Meta-analyses recommendations up to October 2016 using the MESH terms 'right
      colic artery' and 'anatomy' (PROSPERO registration number CRD42016041578).
      RESULTS: Ten studies involving 1073 cadavers were identified as suitable for
      analysis from 211 articles retrieved. The weighted mean incidence with which the
      right colic artery arose from other parent vessels was calculated at 36.8% for
      the superior mesenteric artery, 31.9% for the ileocolic artery, 27.7% for the
      root of the middle colic artery and 2.5% for the right branch of the middle colic
      artery. In 1.1% of individuals the RCA shared a trunk with the middle colic and
      ileocolic arteries. The weighted mean incidence of 2 RCAs was 7.0%, and in 8.9%
      of cadavers the RCA was absent. CONCLUSIONS: This anatomical information will add
      to the technical nuances of precision oncosurgery in right-sided colon
      resections.

PMID- 29196960
TI  - Synergizing community-based forest monitoring with remote sensing: a path to an
      effective REDD+ MRV system.
AB  - BACKGROUND: The reliable monitoring, reporting and verification (MRV) of carbon
      emissions and removals from the forest sector is an important part of the efforts
      on reducing emissions from deforestation and forest degradation (REDD+). Forest
      dependent local communities are engaged to contribute to MRV through community
      based monitoring systems. The efficiency of such monitoring systems could be
      improved through the rational integration of the studies at permanent plots with
      the geospatial technologies. This article presents a case study of integrating
      community-based measurements at permanent plots at the foothills of central Nepal
      and biomass maps that were developed using GeoEye-1 and IKONS satellite images.
      RESULTS: The use of very-high-resolution satellite-based tree cover parameters,
      including crown projected area (CPA), crown density and crown size classes
      improves salience, reliability and legitimacy of the community-based survey of
      0.04% intensity at the lower cost than increasing intensity of the community
      based survey to 0.14% level (2.5 USD/ha vs. 7.5 USD/ha). CONCLUSION: The proposed
      REDD+ MRV complementary system is the first of its kind and demonstrates the
      enhancement of information content, accuracy of reporting and reduction in cost.
      It also allows assessment of the efficacy of community-based forest management
      and extension to national scale.

PMID- 29196961
TI  - alpha7-nAChR Activation Has an Opposite Effect on Healing of Covered and
      Uncovered Wounds.
AB  - The alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) is associated with
      inflammation, re-epithelialization, and angiogenesis in wound healing process. A
      recent study demonstrated that PNU-282987, a selective agonist of alpha7-nAChR,
      accelerates the repair of diabetic excisional wounds. Whether alpha7-nAChR
      activation promotes non-diabetic wounds healing is unknown. The aim of this study
      was to evaluate the effects of alpha7-nAChR activation on non-diabetic wound
      healing. The effects were evaluated in two wound models. In the first model, the
      wound was covered with a semi-permeable transparent dressing. In the second
      model, the wound was left uncovered. In both models, the mice were randomly
      assigned to two treatment groups: saline or PNU282987 (25 mice in each group). In
      covered wounds, we found that alpha7-nAChR activation inhibited re
      epithelialization, angiogenesis, and epithelial cells proliferation, promoted neo
      epithelial detachment, and suppressed neutrophil infiltration and the expression
      of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). However,
      in uncovered wounds, we observed that alpha7-nAChR activation promoted re
      epithelialization and angiogenesis, inhibited neutrophil infiltration and the
      expression of high mobility group box (HMGB)-1, epidermal growth factor (EGF),
      and VEGF. In conclusion, this data demonstrated that alpha7-nAChR activation
      inhibited wound healing in covered wounds but played an opposite role in
      uncovered wounds. The opposite effect might be primarily due to inhibition of
      inflammation.

PMID- 29196962
TI  - The Moral Injury Symptom Scale-Military Version.
AB  - The purpose of this study was to develop a multi-dimensional measure of moral
      injury symptoms that can be used as a primary outcome measure in intervention
      studies that target moral injury (MI) in Veterans and Active Duty Military with
      PTSD. This was a multi-center study of 427 Veterans and Active Duty Military with
      PTSD symptoms recruited from VA Medical Centers in Augusta, Los Angeles, Durham,
      Houston, and San Antonio, and from Liberty University in Lynchburg. Internal
      reliability of the Moral Injury Symptom Scale-Military Version (MISS-M) was
      examined along with factor analytic, discriminant, and convergent validity.
      Participants were randomly split into two equal samples, with exploratory factor
      analysis conducted in the first sample and confirmatory factor analysis in the
      second. Test-retest reliability was assessed in a subsample of 64 Veterans. The
      45-item MISS-M consists of 10 theoretically grounded subscales assessing guilt,
      shame, moral concerns, religious struggles, loss of religious faith/hope, loss of
      meaning/purpose, difficulty forgiving, loss of trust, and self-condemnation. The
      Cronbach's alpha of the overall scale was .92 and of individual subscales ranged
      from .56 to .91. The test-retest reliability was .91 for the total scale and
      ranged from .78 to .90 for subscales. Discriminant validity was demonstrated by
      relatively weak correlations with other psychosocial, religious, and physical
      health constructs, and convergent validity was indicated by strong correlations
      with PTSD, depression, and anxiety symptoms. The MISS-M is a reliable and valid
      multi-dimensional symptom measure of moral injury that can be used in studies
      targeting MI in Veterans and Active Duty Military with PTSD symptoms and may also
      be used by clinicians to identify those at risk.

PMID- 29196963
TI  - Serum lipid and bone metabolism effects of Toremifene vs. Letrozole as adjuvant
      therapy for postmenopausal early breast cancer patients: results of a multicenter
      open randomized study.
AB  - A prospective randomized phase II trial was conducted to evaluate the time course
      effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on
      serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive,
      postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer
      patients [ER positive, HER2 negative, T1-2, node metastases (n = 0-3), M0] who
      had undergone curative resection were enrolled. They were randomized to receive
      either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids
      and bone markers were measured prior to, and again at 6, 12, and 24 months after
      initiation of treatment. Changes in serum lipids and bone markers were compared.
      Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol
      (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and
      14.0% of patients, respectively, receiving TOR. Lipid levels did not change in
      patients administered LET. Significant differences were observed in TC and LDL-C
      between the two groups at 12 and 24 months. In the TOR group, serum bone-specific
      alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross
      linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months,
      and these reductions were maintained for at least 24 months. In contrast, in the
      LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months
      and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert
      different effects on serum lipid profiles and bone metabolism markers. The
      effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism
      in postmenopausal breast cancer patients are superior to those of LET.

PMID- 29196965
TI  - Metabolomic prediction of treatment outcome in pancreatic ductal adenocarcinoma
      patients receiving gemcitabine.
AB  - PURPOSE: Resistance to gemcitabine remains a key challenge in the treatment of
      pancreatic ductal adenocarcinoma (PDAC), necessitating the constant search for
      effective strategies for a priori prediction of clinical outcome. While the
      existing studies focused on aberration of drug disposition genes and proteins as
      molecular predictors of gemcitabine treatment outcomes, the metabolic aberration
      associated with chemoresistance in clinical PDAC has been neglected. This
      exploratory study investigated the potential role of tissue metabolomics in
      characterizing the clinical treatment outcome of gemcitabine therapy. METHODS:
      Surgically resected tumors from PDAC patients who underwent gemcitabine-based
      adjuvant chemotherapy (n = 25) were subjected to metabotyping using gas
      chromatography/time-of-flight mass spectrometry (GC/TOFMS). RESULTS: A partial
      least-squares discriminant analysis (PLS-DA) model clearly distinguished patients
      who had favorable survival [overall survival (OS) > 24 months] from those who
      exhibited poorer survival (OS < 16 months) (Q 2 = 0.302). Receiver-operating
      characteristic analysis demonstrated the robustness of the PLS-DA model with an
      area under the curve of 1. PLS-DA revealed 19 marker metabolites (e.g., lactic
      acid, proline, and pyroglutamate) that shed insights into the chemoresistance of
      gemcitabine in PDAC. Particularly, tissue levels of lactic acid complemented
      transcript expression levels of human equilibrative nucleoside transporter 1 in
      distinguishing patients according to their overall survival. CONCLUSION: This
      work established proof-of-principle for GC/TOFMS-based global metabotyping of
      PDAC and laid the foundation for future discovery of metabolic biomarkers
      predictive of gemcitabine resistance in PDAC chemotherapy.

PMID- 29196964
TI  - The earlier, the better: the effects of different administration timepoints of
      sorafenib in suppressing the carcinogenesis of VEGF in rats.
AB  - PURPOSE: To investigate the optimal starting time point of sorafenib therapy in
      suppressing the tumor-promoting effects of VEGF up-regulation, which is
      frequently found after local therapy in clinical practice. METHODS: VEGF was
      intravenously injected to imitate the evaluated expression after local tumor
      therapy, such as TACE. A total of 40 SD rats bearing hepatic tumors were randomly
      divided into four groups and sorafenib was administered at different timepoints:
      (A) control group: VEGF injection only; (B) initiating sorafenib 72 h prior to
      VEGF injection; (C) initiating sorafenib simultaneously with VEGF injection; (D)
      initiating sorafenib 72 h post-VEGF injection. The rate of tumor growth, median
      survival time, expression of VEGF, and microvessel density (MVD), as determined
      by immunohistochemical (IHC) examination, were compared. RESULTS: The results
      revealed that the tumor size and median survival time were significantly
      different between the three sorafenib groups compared to the control group (p <
      0.05). Median survival times were 19.6 +/- 1.78, 31.2 +/- 6.99, 27.4 +/- 4.9, and
      26.5 +/- 4.6 days in group A, B, C, and D, respectively. Furthermore, there was a
      difference in statistical significance between the two sorafenib groups B and D
      (p = 0.04). Tumors were collected for HE staining and IHC examination. The
      expression levels of VEGF in B, C, and D were 42.8 +/- 7.96, 71.9 +/- 15.73, and
      73.6 +/- 13.73, and all of them were significantly lower than that in the control
      group (88.3 +/- 13.61). Furthermore, the level of MVD was 109.2 +/- 8.98 in the
      control group, which was significantly higher than in the three sorafenib groups
      (45.7 +/- 16.92, 77.1 +/- 16.29, and 93.6 +/- 12.87, all p < 0.05). CONCLUSIONS:
      According to our results, the most suitable regimen for the administration of
      sorafenib is before the increased expression of VEGF, which showed a potential
      advantage for controlling the tumor growth and prolonging the survival time of
      test animal via inhibiting VEGF-receptor expression through the bifunction of
      VEGF, and the reduction of tumor angiogenesis.

PMID- 29196966
TI  - Controlling futures? Online Genetic Testing and Neurodegenerative Disease :
      Comment on "Personal Genomic Testing, Genetic Inheritance, and Uncertainty".
AB  - Online personalized genetic testing services offer accessible and convenient
      options for satisfying personal curiosity about health and obtaining answers
      about one's genetic provenance. They are especially attractive to healthy people
      who wish to learn about their future risk of disease, as Paul Mason's (2017) case
      study of "Jordan" illustrates. In this response, we consider how online genetic
      testing services are used by people diagnosed with a common neurodegenerative
      disease, Parkinson's disease, to gain a sense of certainty regarding the future.

PMID- 29196968
TI  - NK cell therapy after hematopoietic stem cell transplantation: can we improve
      anti-tumor effect?
AB  - After decades since the discovery of natural killer (NK) cells as potential
      effector cells fighting malignantly transformed and virally infected cells,
      little progress has been made in their clinical application. This yet unrealized
      therapeutic effect is presumably, at least in part, due to low numbers of
      functional NK cells that could be obtained from the peripheral blood relative to
      tumor burden. Our group hypothesized that a relatively small NK cell number to
      targeted malignant cells is the cause of a lack of clinical effect. We pursued
      obtaining large numbers of NK cells via ex vivo expansion using feeder cells that
      express membrane-bound IL-21. Early clinical studies demonstrate safety of
      administration of ex vivo expanded NK cells after transplantation using this
      method and suggest a therapeutic benefit in terms on decreasing relapse rate and
      possible control of viral infections post-transplant can be achieved. Successful
      application of NK cells after hematopoietic stem cell transplantation opens the
      possibility to effectively enhance the anti-tumor effect and decrease relapse
      rate post-transplant. Moreover, high doses of NK cells could prove more
      efficacious in enhancing anti-tumor effects, not only in hematological
      malignancies, with our without transplantation, but also in solid tumor oncology.

PMID- 29196969
TI  - Rapid and reliable protein structure determination via chemical shift threading.
AB  - Protein structure determination using nuclear magnetic resonance (NMR)
      spectroscopy can be both time-consuming and labor intensive. Here we demonstrate
      how chemical shift threading can permit rapid, robust, and accurate protein
      structure determination using only chemical shift data. Threading is a relatively
      old bioinformatics technique that uses a combination of sequence information and
      predicted (or experimentally acquired) low-resolution structural data to generate
      high-resolution 3D protein structures. The key motivations behind using NMR
      chemical shifts for protein threading lie in the fact that they are easy to
      measure, they are available prior to 3D structure determination, and they contain
      vital structural information. The method we have developed uses not only sequence
      and chemical shift similarity but also chemical shift-derived secondary
      structure, shift-derived super-secondary structure, and shift-derived accessible
      surface area to generate a high quality protein structure regardless of the
      sequence similarity (or lack thereof) to a known structure already in the PDB.
      The method (called E-Thrifty) was found to be very fast (often < 10
      min/structure) and to significantly outperform other shift-based or threading
      based structure determination methods (in terms of top template model accuracy)
      with an average TM-score performance of 0.68 (vs. 0.50-0.62 for other methods).
      Coupled with recent developments in chemical shift refinement, these results
      suggest that protein structure determination, using only NMR chemical shifts, is
      becoming increasingly practical and reliable. E-Thrifty is available as a web
      server at http://ethrifty.ca .

PMID- 29196967
TI  - Modern iron replacement therapy: clinical and pathophysiological insights.
AB  - Iron deficiency, with or without anemia, is extremely frequent worldwide,
      representing a major public health problem. Iron replacement therapy dates back
      to the seventeenth century, and has progressed relatively slowly until recently.
      Both oral and intravenous traditional iron formulations are known to be far from
      ideal, mainly because of tolerability and safety issues, respectively. At the
      beginning of this century, the discovery of hepcidin/ferroportin axis has
      represented a turning point in the knowledge of the pathophysiology of iron
      metabolism disorders, ushering a new era. In the meantime, advances in the
      pharmaceutical technologies are producing newer iron formulations aimed at
      minimizing the problems inherent with traditional approaches. The pharmacokinetic
      of oral and parenteral iron is substantially different, and diversities have
      become even clearer in light of the hepcidin master role in regulating systemic
      iron homeostasis. Here we review how iron therapy is changing because of such
      important advances in both pathophysiology and pharmacology.

PMID- 29196970
TI  - Endocannabinoid hydrolases in avian HD11 macrophages identified by
      chemoproteomics: inactivation by small-molecule inhibitors and pathogen-induced
      downregulation of their activity.
AB  - The endocannabinoids (eCBs) are endogenous arachidonoyl-containing lipid
      mediators with important roles in host defense. Macrophages are first-line
      defenders of the innate immune system and biosynthesize large amounts of eCBs
      when activated. The cellular levels of eCBs are controlled by the activities of
      their biosynthetic enzymes and catabolic enzymes, which include members of the
      serine hydrolase (SH) superfamily. The physiologic activity of SHs can be
      assessed in a class-specific way using chemoproteomic activity-based protein
      profiling (ABPP) methods. Here, we have examined avian (chicken) HD11
      macrophages, a widely used cell line in host-pathogen research, using gel-based
      ABPP and ABPP-multidimensional protein identification technology (MudPIT) to
      profile the changes in SH activities under baseline, chemical-inhibitor-treated,
      and pathogen-challenged conditions. We identified alpha/beta-hydrolase domain 6
      (ABHD6) and fatty acid amide hydrolase (FAAH) as the principal SHs responsible
      for 2-arachidonoylglycerol (2AG) hydrolysis, thereby regulating the concentration
      of this lipid in HD11 cells. We further discovered that infection of HD11
      macrophages by Salmonella Typhimurium caused the activities of these 2AG
      hydrolases to be downregulated in the host cells. ABHD6 and FAAH were potently
      inhibited by a variety of small-molecule inhibitors in intact live cells, and
      thus these compounds might be useful host-directed adjuvants to combat
      antimicrobial resistance in agriculture. 2AG was further shown to augment the
      phagocytic function of HD11 macrophages, which suggests that pathogen-induced
      downregulation of enzymes controlling 2AG hydrolytic activity might be a
      physiological mechanism to increase 2AG levels, thus enhancing phagocytosis.
      Together these results define ABHD6 and FAAH as 2AG hydrolases in avian
      macrophages that can be inactivated pharmacologically and decreased in activity
      during Salmonella Typhimurium infection.

PMID- 29196971
TI  - Tomatidine inhibits tumor necrosis factor-alpha-induced apoptosis in C2C12
      myoblasts via ameliorating endoplasmic reticulum stress.
AB  - In this study, we examined the effect of tomatidine on tumor necrosis factor
      (TNF)-alpha-induced apoptosis in C2C12 myoblasts. TNF-alpha treatment increased
      cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) protein levels
      in a dose- and time-dependent manner. Pretreatment of cells with 10 MUM
      tomatidine prevented TNF-alpha-induced apoptosis, caspase 3 cleavage, and PARP
      cleavage. Cells were treated with 100 ng/mL TNF-alpha for 24 h, and flow
      cytometry was utilized to assess apoptosis using annexin-V and 7-aminoactinomycin
      D. TNF-alpha up-regulated activating transcription factor 4 (ATF4) and C/EBP
      homologous protein (CHOP) expression. This effect was suppressed by pretreatment
      with tomatidine. Pretreatment with 4-phenylbutyric acid (a chemical chaperone)
      also inhibited TNF-alpha-induced cleavage of caspase 3 and PARP and up-regulation
      of ATF4 and CHOP expression. In addition, tomatidine-mediated inhibition of
      phosphorylation of c-Jun amino terminal kinase (JNK) attenuated TNF-alpha-induced
      cleavage of PARP and caspase 3. However, tomatidine did not affect NF-kappaB
      activation in TNF-alpha-treated C2C12 myoblast cells. Taken together, the present
      study demonstrates that tomatidine attenuates TNF-alpha-induced apoptosis through
      down-regulation of CHOP expression and inhibition of JNK activation.

PMID- 29196972
TI  - Proximal total splenic artery embolization for refractory hepatic encephalopathy.
AB  - A Japanese woman with a history of Kasai operation for biliary atresia had living
      donor liver transplantation at the age of 22. The first episode of refractory HE
      and late cellular rejection was treated by a high dose of methylprednisolone. The
      second episode of refractory HE was treated by balloon-occluded retrograde
      transvenous obliteration for a spleno-renal shunt. However, the third episode of
      refractory HE occurred 11 years after liver transplantation. The liver cirrhosis
      and hypersplenism were present with a Child-Pugh score of C-10. Although portal
      vein flow was hepatopetal, superior mesenteric vein flow regurgitated. We
      performed proximal total splenic artery embolization (TSAE). Superior mesenteric
      vein flow changed to a hepatopetal direction and she became clear. At a year
      after proximal TSAE, her spleen volume had decreased to 589 mL (20% decrease) on
      computed tomography. She is well and has a Child-Pugh score of 8 without overt
      HE. We report the first case of refractory HE treated by proximal TSAE that is a
      possible less invasive treatment option for a selected patient.

PMID- 29196973
TI  - A Novel Homozygous Mutation in SPTBN2 Leads to Spinocerebellar Ataxia in a
      Consanguineous Family: Report of a New Infantile-Onset Case and Brief Review of
      the Literature.
AB  - The objective of this study was the identification of likely genes and mutations
      associated with an autosomal recessive (AR) rare spinocerebellar ataxia (SCA)
      phenotype in two patients with infantile onset, from a consanguineous family.
      Using genome-wide SNP screening, autozygosity mapping, targeted Sanger sequencing
      and nextgen sequencing, family segregation analysis, and comprehensive
      neuropanel, we discovered a novel mutation in SPTBN2. Next, we utilized multiple
      sequence alignment of amino acids from various species as well as crystal
      structures provided by protein data bank (PDB# 1WYQ and 1WJM) to model the
      mutation site and its effect on beta-III-spectrin. Finally, we used various
      bioinformatic classifiers to determine pathogenicity of the missense variant. A
      comprehensive clinical and diagnostic workup including radiological exams were
      performed on the patients as part of routine patient care. The homozygous
      missense variant (c.1572C>T; p.R414C) detected in exon 2 was fully segregated in
      the family and absent in a large ethnic cohort as well as publicly available data
      sets. Our comprehensive targeted sequencing approaches did not reveal any other
      likely candidate variants or mutations in both patients. The two male siblings
      presented with delayed motor milestones and cognitive and learning disability.
      Brain MRI revealed isolated cerebellar atrophy more marked in midline inferior
      vermis at ages of 3 and 6.5 years. Sequence alignments of the amino acids for
      beta-III-spectrin indicated that the arginine at 414 is highly conserved among
      various species and located towards the end of first spectrin repeat domain.
      Inclusive bioinformatic analysis predicted that the variant is to be damaging and
      disease causing. In addition to the novel mutation, a brief literature review of
      the previously reported mutations as well as clinical comparison of the cases
      were also presented. Our study reviews the previously reported SPTBN2 mutations
      and cases. Moreover, the novel mutation, p.R414C, adds up to the literature for
      the infantile-onset form of autosomal recessive ataxia associated with SPTBN2.
      Previously, few SPTBN2 recessive mutations have been reported in humans. Animal
      models especially the beta-III-/- mouse model provided insights into early
      coordination and gait deficit suggestive of loss-of-function. It is expected to
      see more recessive SPTBN2 mutations appearing in the literature during the
      upcoming years.

PMID- 29196974
TI  - The Effects of Gadolinium-Based Contrast Agents on the Cerebellum: from Basic
      Research to Neurological Practice and from Pregnancy to Adulthood.
AB  - Gadolinium (Gd)-based contrast agents (GBCAs) are used in magnetic resonance
      imaging (MRI) to increase the diagnostic yield. Current reports using animal
      models or human subjects have shown that GBCAs may be deposited in brain
      including the cerebellum. Although further studies may be required to clarify the
      toxicity of GBCAs, we should be more cautious to use these agents particularly in
      patients who more likely to have repeated enhanced MRI along their lifespan. In
      this editorial, current studies to clarify the toxicity of GBCAs in the
      cerebellum are introduced.

PMID- 29196975
TI  - Paradoxical Activation in the Cerebellum During Language fMRI in Patients with
      Brain Tumors: Possible Explanations Based on Neurovascular Uncoupling and
      Functional Reorganization.
AB  - The cerebellum is known for its crossed activation pattern with the contralateral
      cerebral hemisphere during language functional magnetic resonance imaging (fMRI)
      tasks in healthy patients. Crossed cerebro-cerebellar activation has been
      previously shown to occur in patients with brain tumors not affecting the
      activation areas. However, the presence of a tumor in left Broca's area in the
      inferior frontal gyrus is known to disrupt cerebral activation during language
      tasks. This study investigated if crossed cerebro-cerebellar activation patterns
      for language tasks would still occur in such patients. A total of 43 right-handed
      patients with a glioma affecting left Broca's area were examined for their
      cerebral and cerebellar activation during an fMRI language task. Only 13 of the
      43 patients exhibited crossed cerebro-cerebellar activation patterns.
      Statistically significant differences of atypical cerebro-cerebellar activation
      patterns were found between cerebral right-dominant (RD) and cerebral co-dominant
      (CD) (p < 0.001) as well as cerebral RD and cerebral left-dominant (LD) patients
      (p < 0.01), while no differences were found when patients were divided based on
      cerebellar dominance (p > 0.75) or tumor grade (p > 0.5). No relation was found
      between the cerebellar and cerebral laterality index (LI) values (rho = - 0.20; p
      = 0.21). Atypical activation patterns are suspected to have been caused by the
      tumor, perhaps a result of contralateral reorganization in some cases and false
      negative activation in left Broca's area from neurovascular uncoupling (NVU) in
      others. Cerebellar activation may also potentially indicate cerebral false
      negative behavior and future cerebral contralateral reorganization.

PMID- 29196976
TI  - Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset
      Spinocerebellar Ataxia Family.
AB  - Mutations in the inositol 1,4,5-triphosphate receptor type 1 gene (ITPR1) lead to
      SCA15, SCA16, and SCA29. To date, only a few families with SCA29 have been
      reported. A three-generation Chinese family including four affected persons and
      two unaffected persons were enrolled in this study. We conducted whole-exome
      sequencing (WES) of the proband DNA initially to find the causal gene. We
      ascertained the family with autosomal dominant type of congenital nonprogressive
      cerebellar ataxia (CNPCA) associated with delayed motor and cognitive impairment.
      WES study was performed with two patients and identified c.1207-2A-T transition,
      in exon 14 of ITPR1, which was a splicing mutation. Sanger sequencing showed that
      four patients within this family carried the mutation and two unaffected members
      did not carry it. The results showed that the novel splicing mutation of ITPR1
      was the causative gene for SCA29. In conclusion, we identified a novel SCA29
      causative splicing mutation of ITPR1 in a Chinese family. We suggest ITPR1 gene
      analysis shall be a priority for diagnosis of patients with early-onset CNPCA.
      Our study demonstrated that whole-exome sequencing might rapidly improve the
      diagnosis of genetic ataxias.

PMID- 29196977
TI  - Self-Organized Cerebellar Tissue from Human Pluripotent Stem Cells and Disease
      Modeling with Patient-Derived iPSCs.
AB  - Recent advances in the techniques that differentiate induced pluripotent stem
      cells (iPSCs) into specific types of cells enabled us to establish in vitro cell
      based models as a platform for drug discovery. iPSC-derived disease models are
      advantageous to generation of a large number of cells required for high
      throughput screening. Furthermore, disease-relevant cells differentiated from
      patient-derived iPSCs are expected to recapitulate the disorder-specific
      pathogenesis and physiology in vitro. Such disease-relevant cells will be useful
      for developing effective therapies. We demonstrated that cerebellar tissues are
      generated from human PSCs (hPSCs) in 3D culture systems that recapitulate the in
      vivo microenvironments associated with the isthmic organizer. Recently, we have
      succeeded in generation of spinocerebellar ataxia (SCA) patient-derived Purkinje
      cells by combining the iPSC technology and the self-organizing stem cell 3D
      culture technology. We demonstrated that SCA6-derived Purkinje cells exhibit
      vulnerability to triiodothyronine depletion, which is suppressed by treatment
      with thyrotropin-releasing hormone and Riluzole. We further discuss applications
      of patient-specific iPSCs to intractable cerebellar disease.

PMID- 29196978
TI  - The Role of Soluble Epoxide Hydrolase Enzyme on Daunorubicin-Mediated
      Cardiotoxicity.
AB  - Several studies have demonstrated the role of cytochrome P450 (CYP) and its
      associated arachidonic acid (AA) metabolites in the anthracyclines-induced
      cardiac toxicity. However, the ability of daunorubicin (DNR) to induce
      cardiotoxicity through the modulation of CYP and its associated AA metabolites
      has not been investigated yet. Therefore, we hypothesized that DNR-induced
      cardiotoxicity is mediated through the induction of cardiotoxic
      hydroxyeicosatetraenoic acids and/or the inhibition of cardioprotctive
      epoxyeicosatrienoic acids (EETs). To test our hypothesis, Sprague-Dawley rats
      were treated with DNR (5 mg/kg i.p.) for 24 h, whereas human ventricular
      cardiomyocytes RL-14 cells were exposed to DNR in the presence and absence of 4
      [[trans-4-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]cyclohexyl]oxy]
      benzoic acid (tAUCB), a soluble epoxide hydrolase (sEH) inhibitor. Thereafter,
      real-time PCR, Western blot analysis and liquid chromatography-electron spray
      ionization mass spectroscopy were used to determine the level of gene expression,
      protein expression and AA metabolites, respectively. Our results showed that DNR
      induced cardiotoxicity in vivo and in vitro as evidenced by the induction of
      hypertrophic and fibrotic markers. Moreover, the DNR-induced cardiotoxicity was
      associated with a dramatic increase in the formation of cardiac DHET/EET
      metabolites both in vivo and in RL-14 cells suggesting a sEH enzyme dependent
      mechanism. Interestingly, inhibition of sEH using tAUCB, a selective sEH
      inhibitor, significantly protects against DNR-induced cardiotoxicity.
      Mechanistically, the protective effect tAUCB was mediated through the induction
      of P50 nuclear factor-kappaB and the inhibition of phosphorylated p38. In
      conclusion, our study provides the first evidence that DNR induces cardiotoxicity
      through a sEH-mediated EETs degradation-dependent mechanism.

PMID- 29196980
TI  - Lessons from the Launch: Program Directors Reflect on Implementing the Child and
      Adolescent Psychiatry Milestones.

PMID- 29196979
TI  - Changes in arterial pressure and markers of nitric oxide homeostasis and
      oxidative stress following surgical correction of hydronephrosis in children.
AB  - OBJECTIVE: Recent clinical studies have suggested an increased risk of elevated
      arterial pressure in patients with hydronephrosis. Animals with experimentally
      induced hydronephrosis develop hypertension, which is correlated to the degree of
      obstruction and increased oxidative stress. In this prospective study we
      investigated changes in arterial pressure, oxidative stress, and nitric oxide
      (NO) homeostasis following correction of hydronephrosis. METHODS: Ambulatory
      arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis
      (n = 15) before and after surgical correction, and the measurements were compared
      with arterial pressure measurements in two control groups, i.e. healthy controls
      (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO
      homeostasis were analyzed in matched urine and plasma samples. RESULTS: The
      preoperative mean arterial pressure was significantly higher in hydronephrotic
      patients [83 mmHg; 95% confidence interval (CI) 80-88 mmHg] than in healthy
      controls (74 mmHg; 95% CI 68-80 mmHg; p < 0.05), and surgical correction of
      ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74-79 mmHg; p <
      0.05). Markers of oxidative stress (i.e., 11-dehydroTXB2, PGF2alpha, 8-iso
      PGF2alpha, 8,12-iso-iPF2alpha-VI) were significantly increased (p < 0.05) in
      patients with hydronephrosis compared with both control groups, and these were
      reduced following surgery (p < 0.05). Interestingly, there was a trend for
      increased NO synthase activity and signaling in hydronephrosis, which may
      indicate compensatory mechanism(s). CONCLUSION: This study demonstrates increased
      arterial pressure and oxidative stress in children with hydronephrosis compared
      with healthy controls, which can be restored to normal levels by surgical
      correction of the obstruction. Once reference data on ambulatory blood pressure
      in this young age group become available, we hope cut-off values can be defined
      for deciding whether or not to correct hydronephrosis surgically.

PMID- 29196981
TI  - Medical-Education-Industrial Complex?

PMID- 29196982
TI  - A Brief Instrument to Assess Both Burnout and Professional Fulfillment in
      Physicians: Reliability and Validity, Including Correlation with Self-Reported
      Medical Errors, in a Sample of Resident and Practicing Physicians.
AB  - OBJECTIVE: The objective of this study was to evaluate the performance of the
      Professional Fulfillment Index (PFI), a 16-item instrument to assess physicians'
      professional fulfillment and burnout, designed for sensitivity to change
      attributable to interventions or other factors affecting physician well-being.
      METHODS: A sample of 250 physicians completed the PFI, a measure of self-reported
      medical errors, and previously validated measures including the Maslach Burnout
      Inventory (MBI), a one-item burnout measure, the World Health Organization's
      abbreviated quality of life assessment (WHOQOL-BREF), and PROMIS short-form
      depression, anxiety, and sleep-related impairment scales. Between 2 and 3 weeks
      later, 227 (91%) repeated the PFI and the sleep-related impairment scale.
      RESULTS: Principal components analysis justified PFI subscales for professional
      fulfillment, work exhaustion, and interpersonal disengagement. Test-retest
      reliability estimates were 0.82 for professional fulfillment (alpha = 0.91), 0.80
      for work exhaustion (alpha = 0.86), 0.71 for interpersonal disengagement (alpha =
      0.92), and 0.80 for overall burnout (alpha = 0.92). PFI burnout measures
      correlated highly (r >= 0.50) with their closest related MBI equivalents. Cohen's
      d effect size differences in self-reported medical errors for high versus low
      burnout classified using the PFI and the MBI were 0.55 and 0.44, respectively.
      PFI scales correlated in expected directions with sleep-related impairment,
      depression, anxiety, and WHOQOL-BREF scores. PFI scales demonstrated sufficient
      sensitivity to detect expected effects of a two-point (range 8-40) change in
      sleep-related impairment. CONCLUSIONS: PFI scales have good performance
      characteristics including sensitivity to change and offer a novel contribution by
      assessing professional fulfillment in addition to burnout.

PMID- 29196984
TI  - Identification of Disease Critical Genes Using Collective Meta-heuristic
      Approaches: An Application to Preeclampsia.
AB  - Identifying a small subset of disease critical genes out of a large size of
      microarray gene expression data is a challenge in computational life sciences.
      This paper has applied four meta-heuristic algorithms, namely, honey bee mating
      optimization (HBMO), harmony search (HS), differential evolution (DE) and genetic
      algorithm (basic version GA) to find disease critical genes of preeclampsia which
      affects women during gestation. Two hybrid algorithms, namely, HBMO-kNN and HS
      kNN have been newly proposed here where kNN (k nearest neighbor classifier) is
      used for sample classification. Performances of these new approaches have been
      compared with other two hybrid algorithms, namely, DE-kNN and SGA-kNN. Three
      datasets of different sizes have been used. In a dataset, the set of genes found
      common in the output of each algorithm is considered here as disease critical
      genes. In different datasets, the percentage of classification or classification
      accuracy of meta-heuristic algorithms varied between 92.46 and 100%. HBMO-kNN has
      the best performance (99.64-100%) in almost all data sets. DE-kNN secures the
      second position (99.42-100%). Disease critical genes obtained here match with
      clinically revealed preeclampsia genes to a large extent.

PMID- 29196983
TI  - Paper Spray Tandem Mass Spectrometry Based on Molecularly Imprinted Polymer
      Substrate for Cocaine Analysis in Oral Fluid.
AB  - This study proposes a new direct and fast method of analysis employing paper
      spray mass spectrometry (PS-MS). The paper used in the proposed method was
      modified with molecularly imprinted polymers (MIP) to create a specific site for
      cocaine analysis in oral fluid. MIP membrane was successfully synthetized and
      employed. The developed method showed to be linear in a concentration range from
      LOQ to 100 ng mL-1. The experimental value of LOQ obtained was 1 ng mL-1. The
      inter-day and intra-day precision and accuracy of the PS-MS method presented
      values lower than 15%. The total recoveries were also evaluated. The PS-MS method
      for the analysis of cocaine in oral fluid showed to be very promising and the
      validation parameters showed a good correlation with the literature. Graphical
      abstract ?.

PMID- 29196985
TI  - Virus-Induced Gene Silencing (VIGS) in Aegilops tauschii and Its Use in
      Functional Analysis of AetDREB2.
AB  - Among the available reverse genetic approaches for studying gene function, virus
      induced gene silencing (VIGS) has several advantages. It allows rapid
      characterization of gene function independent of stable transformation, which is
      basically difficult to achieve in monocots, and offers the potential to silence
      individual or multiple genes of a gene family. In order to establish a VIGS
      system in Aegilops tauschii, modified vectors derived from Barley stripe mosaic
      virus (BSMV) were used for silencing a phytoene desaturase gene that provides a
      convenient visual reporter for silencing. The results demonstrated a high
      efficiency of BSMV-VIGS in A. tauschii. Moreover, the BSMV-VIGS system was used
      to target a 354 bp specific region of the Dehydration-responsive element-binding
      (AetDreb2) gene, resulting in successful silencing of the gene in A. tauschii
      plants, as verified by real-time qRT-PCR. Indeed, in comparison with plants that
      were inoculated with an empty vector (BSMV:00), a faster rate of wilting and a
      lower relative water content were observed in plants inoculated with
      BSMV:AetDreb2 when they were exposed to drought stress. Therefore, BSMV-VIGS can
      be efficiently employed as a novel tool for reverse genetics in A. tauschii. It
      can also be used to study the effects of polyploidization on the gene function by
      a comparative analysis between bread wheat and its diploid progenitor.

PMID- 29196986
TI  - Over-Expression of AtPAP1 Transcriptional Factor Enhances Phenolic Acid
      Production in Transgenic Roots of Leonurus sibiricus L. and Their Biological
      Activities.
AB  - This study examines the production of five phenolic acids (chlorogenic acid,
      neochlorogenic acid, ferulic acid, caffeic acid and p-coumaric acid) following
      over-expression of AtPAP1 transcription factor by four transgenic root clones of
      Leonurus sibiricus after Agrobacterium rhizogenes transformation. The AtPAP1
      expression level was estimated by quantitative real-time PCR. High levels of
      phenolic acids were found in the transgenic roots of L. sibiricus and were
      determined by high-performance liquid chromatography-mass spectrometry analysis.
      Additionally, transgenic roots showed antimicrobial potential and cytotoxic
      activity on glioma cells in IV grade. Our results suggest that L. sibiricus
      transformed roots with AtPAP1 gene over-expression may represent a potential
      source of phenolic acids.

PMID- 29196987
TI  - Underweight status at diagnosis is associated with poorer outcomes in adult
      patients with acute myeloid leukemia: a retrospective study of JALSG AML 201.
AB  - Recent studies have described various impacts of obesity and being overweight on
      acute myeloid leukemia (AML) outcomes in adult patients, but little is known
      about the impact of being underweight. We compared the outcomes of underweight
      patients to those of normal weight and overweight patients. Adult patients with
      AML who registered in the JALSG AML201 study (n = 1057) were classified into
      three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight
      (BMI 18.5-25, n = 746), and overweight (BMI >= 25, n = 219). With the exception
      of age and male/female ratio, patient characteristics were comparable among the
      three groups. Rates of complete remission following induction chemotherapy were
      similar among the three groups (p = 0.68). We observed a significant difference
      in overall survival (OS), disease-free survival (DFS), and non-relapse mortality
      (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p
      = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not
      between underweight and overweight patients. In multivariate analysis,
      underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS
      (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the
      incidences of documented infection (DI) and severe adverse events (AEs) were
      higher in underweight patients than those in normal weight patients (DI 16 vs.
      8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an
      independent adverse prognostic factor for survival in adult AML patients.

PMID- 29196988
TI  - Analysis of Spontaneous Postmarket Case Reports Submitted to the FDA Regarding
      Thromboembolic Adverse Events and JAK Inhibitors.
AB  - INTRODUCTION: The Janus kinase (JAK) inhibitor baricitinib is approved in Europe
      and Japan for the treatment of rheumatoid arthritis. In April 2017, the US FDA
      expressed concern about thromboembolic events (deep venous thrombosis [DVT] and
      pulmonary embolism [PE]) observed in placebo-controlled clinical trials of
      baricitinib. The European and Japanese labels for baricitinib were recently
      updated to include a precaution related to potential thromboembolic events in
      patients at risk. Given that the FDA-approved drugs tofacitinib and ruxolitinib
      are in the same class, we conducted a safety review of the FDA's Adverse Event
      Reporting System (FAERS) to assess postmarketing reporting rates for related
      thromboembolic risks. METHODS: Adverse event (AE) data for tofacitinib,
      tofacitinib extended-release (XR), and ruxolitinib were obtained from the FAERS.
      Reporting odds ratios (RORs) and the R package 'PhViD' to estimate the empirical
      Bayesian geometric mean (EBGM) were used to detect AEs with higher-than-expected
      reporting rates within the FAERS. RESULTS: We did not find evidence in the FAERS
      for elevated reporting rates for DVT and PE across the three JAK inhibitors we
      analyzed. However, multiple drug-AE combinations relating to thromboembolic
      events had both RORs and EBGM values above 1, indicating a trend toward higher
      than-expected reporting rates. For pulmonary thrombosis, the ROR values for
      ruxolitinib, tofacitinib, and tofacitinib XR were 1.46 (95% confidence interval
      [CI] 0.76-2.80), 2.46 (1.55-3.91), and 2.48 (0.80-7.71), respectively, while the
      EBGM values were 1.25 (0.70), 2.46 (1.64), and 1.56 (0.57), respectively.
      Ruxolitinib had ROR values of 4.08 (2.25-7.38) and 1.22 (0.97-1.53) for portal
      vein thrombosis and thrombosis, respectively. The EBGM values for the same drug
      AE combinations were 3.04 (1.79) and 1.16 (0.96). CONCLUSIONS: Our safety review
      of postmarketing FAERS reports associated with three FDA-approved JAK inhibitors
      did not find elevated reporting rates for DVT and PE specifically. However, the
      FAERS data indicated that pulmonary thrombosis may potentially be a class-wide
      issue for JAK inhibitors. Portal vein thrombosis may also be a potential risk for
      ruxolitinib. While these FAERS data add to a growing body of evidence that JAK
      inhibitors may be contraindicated in patients at risk of thromboembolic events,
      the data need to be confirmed by future AE reporting trends, analysis of
      electronic health records, and/or future clinical trials.

PMID- 29196990
TI  - Diagnostic Imaging: Ultrasound.
AB  - Diagnostic ultrasound imaging, particularly that which includes pulsed wave
      Doppler interrogation, is a safe, real-time modality by which the risk of
      developing preeclampsia can be refined, and the effects of established disease
      can be assessed. This chapter outlines the rationale and technique for Doppler
      interrogation of the maternal ophthalmic and uterine arteries and grayscale
      imaging of the maternal optic nerve sheath diameter.

PMID- 29196989
TI  - Mixed Approach Retrospective Analyses of Suicide and Suicidal Ideation for Brand
      Compared with Generic Central Nervous System Drugs.
AB  - INTRODUCTION: Several different types of drugs acting on the central nervous
      system (CNS) have previously been associated with an increased risk of suicide
      and suicidal ideation (broadly referred to as suicide). However, a differential
      association between brand and generic CNS drugs and suicide has not been
      reported. OBJECTIVES: This study compares suicide adverse event rates for brand
      versus generic CNS drugs using multiple sources of data. METHODS: Selected
      examples of CNS drugs (sertraline, gabapentin, zolpidem, and methylphenidate)
      were evaluated via the US FDA Adverse Event Reporting System (FAERS) for a
      hypothesis-generating study, and then via administrative claims and electronic
      health record (EHR) data for a more rigorous retrospective cohort study.
      Disproportionality analyses with reporting odds ratios and 95% confidence
      intervals (CIs) were used in the FAERS analyses to quantify the association
      between each drug and reported suicide. For the cohort studies, Cox proportional
      hazards models were used, controlling for demographic and clinical
      characteristics as well as the background risk of suicide in the insured
      population. RESULTS: The FAERS analyses found significantly lower suicide
      reporting rates for brands compared with generics for all four studied products
      (Breslow-Day P < 0.05). In the claims- and EHR-based cohort study, the adjusted
      hazard ratio (HR) was statistically significant only for sertraline (HR 0.58; 95%
      CI 0.38-0.88). CONCLUSION: Suicide reporting rates were disproportionately larger
      for generic than for brand CNS drugs in FAERS and adjusted retrospective cohort
      analyses remained significant only for sertraline. However, even for sertraline,
      temporal confounding related to the close proximity of black box warnings and
      generic availability is possible. Additional analyses in larger data sources with
      additional drugs are needed.

PMID- 29196991
TI  - Biomarker Immunoassays in the Diagnosis of Preeclampsia: Calculating the
      sFlt1/PlGF Ratio Using the Cobas(r)e 411 Analyser.
AB  - Preeclampsia is a relatively common pregnancy-related condition associated with
      serious maternal and fetal morbidity and mortality. It is now well established
      that anti-angiogenic sFlt1 is upregulated in preeclampsia and binds PlGF and
      VEGF, causing an imbalance in angiogenic factors with subsequent endothelial
      injury and dysfunction. Measurement of placental growth factor (PlGF) and the
      sFlt1/PlGF ratio have both been validated in other countries for screening and
      diagnosis of preeclampsia and the differentiation of preeclampsia from other
      hypertensive disorders of pregnancy. There are several automated, commercially
      available immunoassays capable of measuring PlGF and the sFlt1/PlGF ratio for
      preeclampsia diagnosis. Here we outline the methodology for using the Roche Cobas
      (r) e 411 immunoassay platform to determine the sFlt1/PlGF ratio.

PMID- 29196992
TI  - Assessing the Circulating Placental-Specific Anti-angiogenic Protein sFLT-1 e15a
      in Preeclampsia.
AB  - Preeclampsia is a common obstetric complication globally responsible for a
      significant burden of maternal and perinatal morbidity and mortality. The anti
      angiogenic protein, sFLT-1, plays a central role in its pathophysiology. sFLT-1
      is released from a range of tissues into the circulation, where it antagonizes
      the activity of vascular endothelial growth factor and placental growth factor
      leading to endothelial dysfunction. The resulting widespread endothelial
      dysfunction produces the clinical features of preeclampsia including hypertension
      and proteinuria. Multiple splice variants of sFLT-1 have been identified, with
      one, known as sFLT-1 e15a, present only in humans and higher-order primates. This
      sFLT-1 variant is also the main form of sFLT-1 produced by the placenta. Recent
      work has shown that sFLT-1 e15a is significantly elevated in the placenta and
      circulation of women with preeclampsia. It is also biologically active, capable
      of causing endothelial dysfunction and end-organ dysfunction seen in
      preeclampsia. Indeed, overexpression of sFLT-1 e15a in mice recapitulates the
      preeclamptic phenotype in pregnancy. No commercial assay currently exists to
      analyze sFLT-1 e15a protein levels. Here, a new ELISA method to determine
      circulating sFLT-1 variant levels is described.

PMID- 29196993
TI  - Role of Activin A in the Pathogenesis of Endothelial Cell Dysfunction in
      Preeclampsia.
AB  - This chapter describes the methodologies which may be used in evaluating in vitro
      endothelial cell dysfunction in preeclampsia.

PMID- 29196994
TI  - Genetic Approaches in Preeclampsia.
AB  - Preeclampsia (PE) is a serious hypertensive disorder that affects up to 8% of all
      pregnancies annually. An established risk factor for PE is family history,
      clearly demonstrating an underlying genetic component to the disorder. To date,
      numerous genetic studies, using both the candidate gene and genome-wide approach,
      have been undertaken to tease out the genetic basis of PE and understand its
      origins. Such studies have identified some promising candidate genes such as
      STOX1 and ACVR2A. Nevertheless, researchers face ongoing challenges of
      replicating these genetic associations in different populations and performing
      the functional validation of identified genetic variants to determine their
      causality in the disorder. This chapter will review the genetic approaches used
      in the study of PE, discuss their limitations and possible confounders, and
      describe current strategies.

PMID- 29196995
TI  - Epigenetics and Preeclampsia: Programming of Future Outcomes.
AB  - Pregnancy is known to induce rapid, progressive, and substantial changes to the
      cardiovascular system, ultimately facilitating successful pregnancy outcomes.
      Women who develop hypertensive disorders during pregnancy are considered to have
      "failed" the cardiovascular stress test of pregnancy and likely represent a
      subpopulation with inadequate cardiovascular accommodation. Preeclampsia is a
      serious complication with a myriad of manifestations in both mother and
      offspring. This pregnancy syndrome is a polygenic disease and has now been linked
      to a greater incidence of cardiovascular disease. Moreover, offsprings born to
      preeclamptic mothers exhibit an elevated risk of cardiovascular disease, stroke,
      and mental disorders during adulthood. This suggests that preeclampsia not only
      exposes the mother and the fetus to complications during pregnancy but also
      programs chronic diseases during adulthood in the offspring. The etiology of
      preeclampsia remains unknown, with various theories being suggested to explain
      its origin. It is primarily thought to be associated with poor placentation and
      entails excessive maternal inflammation and endothelial dysfunction. It is well
      established now that the maternal immune system and the placenta are involved in
      a highly choreographed cross talk that underlies adequate spiral artery
      remodeling required for uteroplacental perfusion and free flow of nutrients to
      the fetus. Although it is not clear whether immunological alterations occur early
      during pregnancy, studies have proposed that dysregulated systemic and placental
      immunity contribute to impaired angiogenesis and the onset of preeclampsia.
      Recently emerged strong evidence suggests a potential link among epigenetics,
      microRNAs (miRNAs), and pregnancy complications. This chapter will focus on
      important aspects of epigenetics, immunological aspects, and cardiovascular and
      vascular remodeling of preeclampsia.

PMID- 29196996
TI  - Inflammatory and Immune System Markers.
AB  - Since preeclampsia was first described by Hippocrates in 400 BC, the theory of
      its causation has shifted from toxins to a current theory that incorporates both
      vascular and immunological causation. Poor placentation whether it is genetically
      predisposed or due to low expression of defective HLA-G on fetal trophoblasts is
      believed to be the initial insult. Oxidative stress from placental
      ischemia/hypoxia leads to an overload of trophoblast debris by stimulating
      apoptosis or necrosis. Partial failure of the maternal immune system to tolerate
      the paternal alloantigens activates maternal immune cells to secrete cytokines
      whose pleiotropic functions lead to dysfunction of the maternal vascular and
      placental endothelium, blood coagulation, and fibrinolytic system. This chapter
      describes some of the key methodologies (flow cytometry, ELISAs, and multiplex
      immunoassays) for the identification and quantification of inflammation and
      immune system markers in the study of preeclampsia pathogenesis, as well as
      diagnostic and therapeutic development. The methodologies may be utilized for a
      variety of tissue sources in the study of preeclampsia: maternal peripheral
      blood, umbilical cord blood, intervillous blood, decidua, chorionic villous,
      amnion and chorion membranes, and cell culture supernatant.

PMID- 29196997
TI  - Methods to Enrich Exosomes from Conditioned Media and Biological Fluids.
AB  - Exosomes are nano-vesicles which can transport a range of molecules including but
      not limited to proteins and miRNA. This ability of exosomes renders them useful
      in cellular communication often resulting in biological changes. They have
      several functions in facilitating normal biological processes such as immune
      responses and an involvement in pregnancy. However, they have also been linked to
      pathological conditions including cancer and pregnancy complications such as
      preeclampsia. An understanding for the role of exosomes in preeclampsia is based
      on the ability to purify and characterize exosomes. There have been several
      techniques proposed for the enrichment of exosomes such as ultracentrifugation,
      density gradient separation, and ultrafiltration although there is no widely
      accepted optimized technique. Here we describe a workflow for isolating exosomes
      from cell-conditioned media and biological fluids using a combination of
      centrifugation, buoyant density, and ultrafiltration approaches.

PMID- 29196998
TI  - Isolation and Characterization of Extracellular Vesicles from Ex Vivo Cultured
      Human Placental Explants.
AB  - Ex vivo culture of human placental explants has long allowed placentologists to
      study the milieu of soluble factors secreted by the human placenta throughout
      gestation while retaining the correct three-dimensional structure of the
      placental villi. Here, we detail the placental explant culture method employed in
      our laboratory to collect extracellular vesicles which are known to be released
      by the human placenta throughout pregnancy from 6 weeks of gestation. Using this
      method, at least three different populations of placental extracellular vesicles
      can be simultaneously collected from each placental sample, allowing for
      comparative analysis of the cargos and downstream effects of the different types
      of extracellular vesicles produced by the human placenta.

PMID- 29196999
TI  - Optimized Specific Isolation of Placenta-Derived Exosomes from Maternal
      Circulation.
AB  - Exosomes are small (~100 nm) vesicles that carry a wide range of molecules
      including proteins, RNAs, and DNA. Exosomes are secreted from a wide range of
      cells including placental cells. Interestingly, exosomes secreted from placental
      cells have been identified in maternal circulation as early as in 6 weeks of
      gestation, and their concentration increases with the gestational age. While
      there is growing interest in elucidating the role of exosomes during normal and
      complicated pregnancies (such as preeclampsia), progress in the field has been
      delayed because of the inability to isolate placental exosomes from maternal
      circulation. Therefore, here we describe a workflow to isolate placental exosomes
      from maternal circulation.

PMID- 29197000
TI  - Proteomics Method to Identification of Protein Profiles in Exosomes.
AB  - Exosomes are membrane-bound nanovesicles that transport molecular signals (e.g.,
      proteins) between cells and are released from a wide range of cells, including
      the human placenta. Interestingly, the levels of exosomes present in maternal
      circulation are higher in preeclamptic pregnancies and their protein content
      profile change in response to the microenvironment milieu. Through the discovery
      of candidate biomarkers, mass spectrometry (MS)-based proteomics may provide a
      better understanding of the pathophysiology underlying pregnancy-associated
      disorders. With advances in sample preparation techniques, computational
      methodologies, and bioinformatics, MS-based proteomics have addressed the
      challenge of identifying and quantifying thousands of proteins and peptides from
      a variety of complex biological samples. Despite increasing interest in biomarker
      diagnostics, the complex nature of biological matrices (e.g., plasma) poses a
      challenge for candidate biomarker discovery. Here we describe a workflow to
      prepare exosomes for proteomic analysis.

PMID- 29197001
TI  - Harvesting and Characterization of Syncytial Nuclear Aggregates Following Culture
      of First Trimester Human Placental Explants.
AB  - There is currently no effective method to study multinucleated trophoblast debris
      extruded from the syncytiotrophoblast into the maternal circulation. In Chapter 9
      , an in vitro placental explant culture model to generate trophoblast debris was
      described. Here, we detail the method utilized to isolate individual large
      multinucleated syncytial nuclear aggregates (SNAs) that are extruded from the
      syncytiotrophoblast following the culture of first trimester human placental
      explants. Syncytial nuclear aggregates have been observed in the peripheral
      maternal circulation as early as 6 weeks' gestation and may play a role in
      tolerating the maternal immune system during pregnancy. Conversely, aberrant cell
      death processes in the syncytiotrophoblast due to various maternal factors
      leading to the extrusion of SNAs that are altered in nature have been implicated
      in the development of preeclampsia. The methods described herein allow for the
      isolation and harvest of SNAs without other types of extruded trophoblast debris
      and can be used to investigate the effect of various maternal factors on the
      nature of SNAs extruded from the placenta in vitro.

PMID- 29197002
TI  - Use of GATA3 and TWIST1 Immunofluorescence Staining to Assess In Vitro Syncytial
      Fusion Index.
AB  - In human placenta, the multinucleated syncytiotrophoblast (ST) allows all the
      exchanges between the maternal and fetal circulation and is also the site of
      placental hormonal functions. Absence or disturbances of ST formation are
      associated with a defect or pathologies of pregnancy such as preeclampsia (PE)
      and intrauterine growth retardation (IUGR). All along pregnancy, the ST is
      regenerated by fusion of underlying mononucleated villous cytotrophoblasts (VCT).
      The protocol described here provides details on how GATA3 or TWIST1
      immunostaining and analysis can be used to easily assess the in vitro
      differentiation of human placental cytotrophoblast.

PMID- 29197003
TI  - Ex Vivo Dual Perfusion of the Human Placenta: Disease Simulation, Therapeutic
      Pharmacokinetics and Analysis of Off-Target Effects.
AB  - In recent years ex vivo dual perfusion of the human placental lobule is seeing an
      international renaissance in its application to understanding fetal health and
      development. Here, we discuss the methods and uses of this technique in the
      evaluation of (1) vascular function, (2) transplacental clearance, (3)
      hemodynamic and oxygenation changes associated with pregnancy complications on
      placental structure and function, and (4) placental toxicology and post-perfusion
      evaluation of tissue architecture.

PMID- 29197004
TI  - Immunohistological Techniques.
AB  - Preeclampsia is associated with histological alterations in the placenta. These
      alterations can be described by means of histological techniques. More
      specifically, immunohistochemistry could be used to detect proteins, and these in
      turn may be used to identify a specific cell type, to differentiate it from other
      cell types and to detect the expression of some markers deregulated in
      preeclampsia.This chapter focuses on the detection of specific cellular and
      molecular markers that evidence the alterations in the human placenta in
      preeclampsia.

PMID- 29197005
TI  - Using a Next-Generation Sequencing Approach to Profile MicroRNAs from Human
      Origin.
AB  - Next-generation sequencing is a powerful method to interrogate the nucleotide
      composition for millions of DNA strands simultaneously. This technology can be
      utilized to profile microRNAs from multiple origins, such as tissues, cells, and
      body fluids. Next-generation sequencing is increasingly becoming a common and
      readily available technique for all laboratories. However, the bottleneck for
      next-generation sequencing is not within the laboratory but with the
      bioinformatics and data analysis of next-generation sequencing data. This chapter
      briefly describes the methods used to prepare samples for next-generation
      sequencing within the laboratory, before a deeper description of the methods used
      for data analysis.

PMID- 29197006
TI  - Isolation and Purification of Villous Cytotrophoblast Cells from Term Human
      Placenta.
AB  - The placenta is a key element during pregnancy for the health of the fetus and
      the mother, which justifies why placental studies are so important. One of the
      best models for placental studies is the primary cell culture of cytotrophoblast
      cells from human term placentas. In this chapter, we will detail firstly the
      isolation of cytotrophoblast cells, with tissue preparation, digestion, Percoll
      gradient, and cell freezing, and secondly the cell immunopurification and
      seeding.

PMID- 29197007
TI  - Analyzing Trophoblast Function Using Cell-Based Assays.
AB  - Functional cell-based assays are useful for comparing the effect of a treatment,
      drug, or condition on cells in culture. Cell lines are a commonly used model to
      replicate a normal biological process or a pathological condition. Trophoblasts
      within the placenta are required to perform a variety of functions, which include
      proliferation, differentiation, migration, and invasion for efficient
      placentation to occur. These functions are impaired in trophoblasts from
      preeclamptic pregnancies, and therefore functional cell-based assays can be
      utilized to measure differences and dissect molecular regulatory pathways.

PMID- 29197008
TI  - Isolation and Characterization of Mesenchymal Stem/Stromal Cells Derived from
      Human Third Trimester Placental Chorionic Villi and Decidua Basalis.
AB  - The decidua basalis and placental chorionic villi are critical components of
      maternal-fetal interface, which plays a critical role in normal placental
      development. Failure to form a proper maternal-fetal interface is associated with
      clinically important placental pathologies including preeclampsia and fetal
      growth restriction. Placental trophoblast cells are well known for their critical
      roles in establishing the maternal-fetal interface; however accumulating evidence
      also implicates mesenchymal stem/stromal cells that envelop the maternal and
      fetal blood vessels as playing an important role in the formation and efficient
      functioning of the interface. Moreover, recent studies associate abnormal
      mesenchymal stem/stromal cell function in the development of preeclampsia.
      Further research is needed to fully understand the role that these cells play in
      this clinically important placental pathology.The intimate relationship between
      maternal and fetal tissues at the interface poses significant problems in the
      enrichment of decidua basalis and chorionic villous mesenchymal stem/stromal
      cells without significant cross-contamination. The protocols described below for
      the enrichment and characterization of mesenchymal stem/stromal cells from the
      maternal-fetal interface produce highly enriched cells that conform to
      international standards and show minimal cross-contamination.

PMID- 29197009
TI  - An Electrical Impedance-Based Assay to Examine Functions of Various Placental
      Cell Types In Vitro.
AB  - In vitro functional analyses of cells are widely used to investigate the
      molecular mechanisms involved in preeclampsia. Common cellular functions studied
      include adhesion, apoptosis, proliferation, migration, and invasion. At present,
      most researchers will use endpoint experimental assays that only allow the
      determination of cell function at a single time point, with the need to repeat
      the experiment for an alternate time point. Here, we describe an electrical
      impedance-based tool that allows real-time monitoring of cells, which enables the
      efficient assessment of multiple time points over the duration of a single
      experiment.

PMID- 29197010
TI  - In Vitro Induction of Hypoxia/Reoxygenation on Placental Cells: A Suitable Model
      for Understanding Placental Diseases.
AB  - Lack of blood flow and aberrant levels of oxygenation in placentas are recurrent
      in pregnancy diseases, such as preeclampsia. These alterations generate
      situations of hypoxia and hypoxia/reoxygenation (H/R) and consequent oxidative
      stress, increased cell death, and inflammation in trophoblasts. The models used
      to understand the effects of hypoxia and H/R on trophoblasts require a rather big
      structure. This chapter describes the details of a suitable and reasonable
      approach with hypoxia chambers to expose human placental trophoblasts to variable
      conditions of oxygenation.

PMID- 29197011
TI  - Measurement of Oxidative Stress: Mitochondrial Function Using the Seahorse
      System.
AB  - The Seahorse XFp Analyzer is a powerful tool for the assessment of various
      parameters of cellular respiration. Here we describe the process of the Seahorse
      Cell Phenotype Test using the Seahorse XFp Analyzer to characterize the metabolic
      phenotype of live cells. The Seahorse XFp Analyzer can also be coupled with other
      assays to measure cellular energetics. Given that mitochondrial dysfunction is
      implicated in preeclampsia, the Seahorse XFp Analyzer will serve as a useful tool
      for the understanding of pathological metabolism in this disorder.

PMID- 29197012
TI  - Co-culture of H295R Adrenocortical Carcinoma and BeWo Choriocarcinoma Cells to
      Study Feto-placental Interactions: Focus on Estrogen Biosynthesis.
AB  - Estrogens are produced in large amounts during pregnancy, as a result of a
      tightly regulated cooperation between the maternal and fetal adrenal cortex,
      which produce androgen precursors, and the placental villous trophoblast, which
      transforms these precursors into estrogens. These estrogens play an important
      role in proper placental function, in adaptation of the mother to pregnancy, as
      well as in adequate fetal development. Disruption of estrogen production is
      associated with poor pregnancy outcomes and fetal malformation or altered fetal
      programming. Pregnant women may be exposed to endocrine disruptors from
      environmental sources or medications, and it is crucial to study the effects of
      such compounds on feto-placental steroidogenesis. The H295R/BeWo co-culture model
      offers the opportunity to study these interactions, by making it possible to
      evaluate the effects of chemical exposures on androgen and estrogen biosynthesis,
      as well as on various other aspects of feto-placental communication.

PMID- 29197013
TI  - Placental Lipid Transport.
AB  - The human placenta is responsible for the adequate supply of nutrients essential
      for proper embryonic and fetal development such as glucose, amino acids, and
      lipids. Processes involved in the placental transport of these nutrients are
      complex and tightly regulated and involve many transporters, receptors, and
      regulators. In this chapter, we describe the current methods to study the impact
      of maternal metabolic disorders on key players of human placental transfer of
      nutrients.

PMID- 29197014
TI  - EG-VEGF Maintenance Over Early Gestation to Develop a Pregnancy-Induced
      Hypertensive Animal Model.
AB  - During the last decade, multiple animal models have been developed to mimic
      hallmarks of pregnancy-induced hypertension (PIH) diseases, which include
      gestational hypertension, preeclampsia (PE), or eclampsia. Converging in vitro,
      ex vivo, and clinical studies from our group strongly suggested the potential
      involvement of the new angiogenic factor EG-VEGF (endocrine gland-derived-VEGF)
      in the development of PIH. Here, we described the protocol that served to
      demonstrate that maintenance of EG-VEGF production over 11.5 days post coitus
      (dpc) in the gravid mice caused the development of PIH. The developed model
      exhibited most hallmarks of preeclampsia.

PMID- 29197015
TI  - Real-Time Blood Pressure Recording Using Radiotelemetry in a Rat Model of
      Preeclampsia.
AB  - Radiotelemetry is increasingly being recognized not just as the gold standard but
      a necessity for validation of gestational hypertension seen in preeclampsia. Here
      we describe radiotelemetry probe implantation into the descending aorta of
      Sprague-Dawley rats to allow real-time blood pressure recording over the entire
      gestational period. This is a valuable tool to be able to track changes in
      maternal blood pressure throughout gestation and the efficacy of novel
      therapeutic agents in controlling hypertension.

PMID- 29197016
TI  - Phase I Pilot Clinical Trial of Antenatal Maternally Administered Melatonin to
      Decrease the Level of Oxidative Stress in Human Pregnancies Affected by
      Preeclampsia.
AB  - This chapter describes the methodologies which may be used in the development of
      a phase I clinical trial investigating a therapy of choice in treating
      preeclampsia.

PMID- 29197017
TI  - A Randomized Double-Blinded Placebo-Controlled Intervention Trial of Melatonin
      for the Prevention of Preeclampsia in Moderate- and High-Risk Women: The MELPOP
      Trial.
AB  - This chapter describes the methodologies which may be used in the development of
      a randomized controlled trial investigating a therapy of choice in preventing
      preeclampsia.

PMID- 29197018
TI  - [Rare incidental finding in the hepatoduodenal ligament : Case report and review
      of the literature].

PMID- 29197019
TI  - [Quality indicators for pancreatic surgery : Scientific derivation and clinical
      relevance].
AB  - Quality indicators are by definition indirect measures of quality. The selection
      for the field of pancreatic surgery was based on the clinical relevance and
      controllability, scientific evidence and the practicability of data acquisition.
      In terms of outcome quality, hospital mortality, the composite endpoint MTL30
      (mortality-transfer-length of stay), and major complications (Clavien-Dindo
      classification grades 3b and 4) were chosen as being essential. With respect to
      structural quality, the presence of interventional radiology with constant
      availability was considered essential. To evaluate target values two strategies
      were used: a systematic literature search and evaluation of the current numbers
      from the German Society for General and Visceral Surgery (DGAV) StuDoQ|Pancreas
      registry for the years 2014-2016. The results are presented in the following
      consensus statement.

PMID- 29197020
TI  - Quality of life in sarcopenia measured with the SarQoL(r): impact of the use of
      different diagnosis definitions.
AB  - BACKGROUND: The SarQoL(r) is a recently developed quality of life questionnaire
      specific to sarcopenia. AIM: To compare the quality of life (QoL) of subjects
      identified as sarcopenic with that of non-sarcopenic subjects when using six
      different operational definitions of sarcopenia. METHODS: Participants of the
      SarcoPhAge study (Belgium) completed the SarQoL(r). Among the six definitions
      used, two were based on low lean mass alone (Baumgartner, Delmonico), and four
      required both low muscle mass and decreased performance (Cruz-Jentoft, Studenski,
      Fielding, Morley). Physical assessments included measurements of muscle mass with
      dual energy X-ray absorptiometry, muscle strength with a handheld dynamometer and
      gait speed over a 4-m distance. RESULTS: A total of 387 subjects completed the
      SarQoL(r). Prevalence of sarcopenia varied widely across the different
      definitions. Using the SarQoL(r), a lower QoL was found for sarcopenic subjects
      compared to non-sarcopenic subjects when using the definitions of Cruz-Jentoft
      (56.3 +/- 13.4 vs 68.0 +/- 15.2, p < 0.001), Studenski (51.1 +/- 14.5 vs 68.2 +/-
      14.6, p < 0.001), Fielding (53.8 +/- 12.0 vs 68.3 +/- 15.1, p < 0.001), and
      Morley (53.3 +/- 12.5 vs 67.1 +/- 15.3, p < 0.001). No QoL difference between
      sarcopenic and non-sarcopenic subjects was found when using the definitions of
      Baumgartner or Delmonico, which were only based on the notion of decreased muscle
      mass. DISCUSSION AND CONCLUSIONS: The SarQoL(r) was able to discriminate
      sarcopenic from non-sarcopenic subjects with regard to their QoL, regardless of
      the definition used for diagnosis as long as the definition includes an
      assessment of both muscle mass and muscle function. Poorer QoL, therefore, seems
      more related to muscle function than to muscle mass.

PMID- 29197021
TI  - How to accelerate the upper urinary stone discharge after extracorporeal
      shockwave lithotripsy (ESWL) for < 15 mm upper urinary stones: a prospective
      multi-center randomized controlled trial about external physical vibration
      lithecbole (EPVL).
AB  - OBJECTIVE: To asset the efficacy and safety of EPVL plus ESWL compared with ESWL
      alone for the treatment of simple upper urinary stones (< 15 mm). MATERIALS AND
      METHODS: All patients with upper urinary stones (< 15 mm) were prospectively
      randomized into two groups. In treatment group, patients were assigned to
      immediate EPVL after ESWL, while in control group, ESWL alone was offered. All
      patients were reexamined at 1, 2, and 4 weeks after ESWL. Stone size, stone
      location, stone-free rate (SFR), and complication rate were compared. RESULTS: 56
      males and 20 females in treatment group were compared to 52 male and 25 females
      in control group (p = 0.404). Median ages were 42.9 +/- 1.5 years in treatment
      group and 42.7 +/- 1.3 years in control group (p = 0.943). Median stone size was
      10.0 +/- 0.4 mm (3-15 mm) in treatment group and 10.4 +/- 0.4 mm (4-15 mm) in
      control group (p = 0.622). The stone clearance rate in treatment and control
      group at 1 week after ESWL was 51.3% (39/76) and 45.4% (35/77) (p > 0.05), at 2
      weeks was 81.6% (62/76) and 64.9% (50/77) (p < 0.05), and at 4 weeks was 90.8%
      (69/76) and 75.3% (58/77) (p < 0.05), respectively. CONCLUSIONS: EPVL is a
      noninvasive, effective, and safe adjunctive treatment which increases and
      accelerates upper urinary stones discharge after ESWL treatment.

PMID- 29197023
TI  - Cerebral and spinal cavernomas associated with Klippel-Trenaunay syndrome: case
      report and literature review.
AB  - Klippel-Trenaunay-Weber syndrome (KTWS) involves a triad of conditions, including
      cutaneous hemangiomas, venous varicosities, and osseous and soft-tissue
      hypertrophy of the affected limb. We describe a rare case of multiple cavernomas
      in the central nervous system in a patient with KTWS. A-64-year-old man with KTWS
      and a previous brain hemorrhage presented with sudden onset of gait and
      vesicorectal disturbance. The magnetic resonance imaging scan showed a cavernoma
      associated with hemorrhage in his lumbosacral spinal cord. Moreover, numerous
      cavernomas were identified in his brain. He was treated conservatively with no
      adverse events. Gait disturbance improved, but vesicorectal disturbance did not
      improve.

PMID- 29197022
TI  - Endosymbiont CLS-HI plays a role in reproduction and development of Haemaphysalis
      longicornis.
AB  - Coxiella-like endosymbiont (CLS-Hl) is a primary endosymbiont of Haemaphysalis
      longicornis. CLS-Hl infects tick special tissues and its prevalence is 100% in
      ovaries and Malpighian tubules. Tetracycline was injected into females, which
      then fed on rabbits also treated with tetracycline. The densities of CLS-Hl were
      measured by semi-quantitative PCR. CLS-Hl densities in ovaries and Malpighian
      tubes of H. longicornis had significant effects on engorged weight, feeding time,
      number of eggs, oviposition period, and hatching period. These findings suggested
      that CLS-Hl plays a role in the reproduction and development of H. longicornis.

PMID- 29197024
TI  - Impact of incomplete ventricular coverage on diagnostic performance of myocardial
      perfusion imaging.
AB  - In the context of myocardial perfusion imaging (MPI) with cardiac magnetic
      resonance (CMR), there is ongoing debate on the merits of using technically
      complex acquisition methods to achieve whole-heart spatial coverage, rather than
      conventional 3-slice acquisition. An adequately powered comparative study is
      difficult to achieve given the requirement for two separate stress CMR studies in
      each patient. The aim of this work is to draw relevant conclusions from SPECT MPI
      by comparing whole-heart versus simulated 3-slice coverage in a large existing
      dataset. SPECT data from 651 patients with suspected coronary artery disease who
      underwent invasive angiography were analyzed. A computational approach was
      designed to model 3-slice MPI by retrospective subsampling of whole- heart data.
      For both whole-heart and 3-slice approaches, the diagnostic performance and the
      stress total perfusion deficit (TPD) score-a measure of ischemia extent/severity
      were quantified and compared. Diagnostic accuracy for the 3-slice and whole-heart
      approaches were similar (area under the curve: 0.843 vs. 0.855, respectively; P =
      0.07). The majority (54%) of cases missed by 3-slice imaging had primarily apical
      ischemia. Whole-heart and 3-slice TPD scores were strongly correlated (R2 = 0.93,
      P < 0.001) but 3-slice TPD showed a small yet significant bias compared to whole
      heart TPD (- 1.19%; P < 0.0001) and the 95% limits of agreement were relatively
      wide (- 6.65% to 4.27%). Incomplete ventricular coverage typically acquired in 3
      slice CMR MPI does not significantly affect the diagnostic accuracy. However, 3
      slice MPI may fail to detect severe apical ischemia and underestimate the
      extent/severity of perfusion defects. Our results suggest that caution is
      required when comparing the ischemic burden between 3-slice and whole-heart
      datasets, and corroborate the need to establish prognostic thresholds specific to
      each approach.

PMID- 29197025
TI  - German cardiac CT registry: indications, procedural data and clinical
      consequences in 7061 patients undergoing cardiac computed tomography.
AB  - Cardiac computed tomography permits quantification of coronary calcification as
      well as detection of coronary artery stenoses after contrast enhancement.
      Moreover, cardiac CT offers high-resolution morphologic and functional imaging of
      cardiac structures which is valuable for various structural heart disease
      interventions and electrophysiology procedures. So far, only limited data exist
      regarding the spectrum of indications, image acquisition parameters as well as
      results and clinical consequences of cardiac CT examinations using state-of-the
      art CT systems in experienced centers. Twelve cardiology centers with profound
      expertise in cardiovascular imaging participated in the German Cardiac CT
      Registry. Criteria for participation included adequate experience in cardiac CT
      as well of the availability of a 64-slice or newer CT system. Between 2009 and
      2014, 7061 patients were prospectively enrolled. For all cardiac CT examinations,
      patient parameters, procedural data, indication and clinical consequences of the
      examination were documented. Mean patient age was 61 +/- 12 years, 63% were
      males. The majority (63%) of all cardiac CT examinations were performed in an
      outpatient setting, 37% were performed during an inpatient stay. 91% were
      elective and 9% were scheduled in an acute setting. In most examinations (48%),
      reporting was performed by cardiologists, in 4% by radiologists and in 47% of the
      cases as a consensus reading. Cardiac CT was limited to native acquisitions for
      assessment of coronary artery calcification in 9% of patients, only contrast
      enhanced coronary CT angiography was performed in 16.6% and combined native and
      contrast-enhanced coronary CT angiography was performed in 57.7% of patients. Non
      coronary cardiac CT examinations constituted 16.6% of all cases. Coronary artery
      calcification assessment was performed using prospectively ECG-triggered
      acquisition in 76.9% of all cases. The median dose length product (DLP) was 42
      mGy cm (estimated effective radiation dose of 0.6 mSv). Coronary CT angiography
      was performed using prospectively ECG-triggered acquisition in 77.3% of all
      cases. Tube voltage was 120 kV in 67.8% of patients and 100 kV in 30.7% of
      patients, with a resultant median DLP of 256 mGy cm (estimated effective dose of
      3.6 mSv). Clinical consequences of cardiac CT were as follows: in 46.8% of the
      cases, invasive coronary angiography could be avoided; ischemia testing was
      recommended in 4.7% of the cases, invasive coronary angiography was recommended
      in 16.4% of the cases and change in medication in 21.6% of the examinations.
      Cardiac CT is performed in the majority of patients for non-invasive evaluation
      of the coronary arteries. CT frequently resulted in medication change, and
      otherwise planned downstream testing including invasive angiography could be
      avoided in a high percentage of patients. Radiation exposure in experienced
      centers is relatively low.

PMID- 29197026
TI  - An expression atlas of miRNAs in Arabidopsis thaliana.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate a variety of
      biological processes. MiRNA expression often exhibits spatial and temporal
      specificity. However, genome-wide miRNA expression patterns in different organs
      during development of Arabidopsis thaliana have not yet been systemically
      investigated. In this study, we sequenced small RNA libraries generated from 27
      different organ/tissue types, which cover the entire life cycle of Arabidopsis.
      Analysis of the sequencing data revealed that most miRNAs are ubiquitously
      expressed, whereas a small set of miRNAs display highly specific expression
      patterns. In addition, different miRNA members within the same family have
      distinct spatial and temporal expression patterns. Moreover, we found that some
      miRNAs are produced from different arms of their hairpin precursors at different
      developmental stages. This work provides new insights into the regulation of
      miRNA biogenesis and a rich resource for future investigation of miRNA functions
      in Arabidopsis.

PMID- 29197028
TI  - Best practices for authenticating cell lines.
AB  - Experiments using cell cultures are only valid to the extent that the cell
      culture is a true model system for the biological system being investigated. To
      assure that a cell line is and remains an appropriate biological model, its
      identity, purity, ploidy, and phenotype must be maintained. These characteristics
      comprise and determine the authenticity of a cell line. Routine monitoring of the
      cell line through microscopic examination of morphology can help to determine
      authenticity, as can the determination of phenotypic status. Assays designed to
      confirm cell identity and ploidy and freedom from cross-contaminating cell types
      may need to be performed at certain times, as such information may not be
      obtained through morphologic and phenotypic examinations alone. The best
      practices associated with establishing cell line authenticity are described in
      this article.

PMID- 29197027
TI  - Best practices for detecting and mitigating the risk of cell culture
      contaminants.
AB  - A variety of biological and chemical contaminants can adversely impact cells in
      culture, ranging from outright destruction of the culture, mutation, phenotypic
      changes to relatively minor changes in morphology, or growth rate. There are
      various approaches to detecting and mitigating the risk of biological or
      microbial contaminants in cell cultures, and these are discussed in this article.
      Chemical contaminants typically arise from improper handling or sourcing of cell
      culture reagents, glassware, or other types of consumables. These and other
      sources of chemical contaminants of cell cultures are discussed. The occurrence
      of chemical contamination is mitigated through adherence to best practices in
      sourcing and handling of such materials and by avoiding the use of volatile
      solvents within incubators that are used for maintaining cell cultures.

PMID- 29197029
TI  - Vasculogenic and angiogenic potential of adipose stromal vascular fraction cell
      populations in vitro.
AB  - Adipose-derived stromal vascular fraction (SVF) is a heterogeneous cell source
      that contains endothelial cells, pericytes, smooth muscle cells, stem cells, and
      other accessory immune and stromal cells. The SVF cell population has been shown
      to support vasculogenesis in vitro as well vascular maturation in vivo. Matrigel,
      an extracellular matrix (ECM) mixture has been utilized in vitro to evaluate tube
      formation of purified endothelial cell systems. We have developed an in vitro
      system that utilizes freshly isolated SVF and ECM molecules both in pure form
      (fibrin, laminin, collagen) as well as premixed form (Matrigel) to evaluate
      endothelial tip cell formation, endothelial stalk elongation, and early stages of
      branching and inosculation. Freshly isolated SVF rat demonstrate cell aggregation
      and clustering (presumptive vasculogenesis) on Matrigel ECM within the first 36 h
      of seeding followed by tip cell formation, stalk cell formation, branching, and
      inosculation (presumptive angiogenesis) during the subsequent 4 days of culture.
      Purified ECM molecules (laminin, fibrin, and collagen) promote cell proliferation
      but do not recapitulate events seen on Matrigel. We have created an in vitro
      system that provides a functional assay to study the mechanisms of vasculogenesis
      and angiogenesis in freshly isolated SVF to characterize SVF's blood vessel
      forming potential prior to clinical implantation.

PMID- 29197030
TI  - Identification of key genes fluctuated induced by avian leukemia virus (ALV-J)
      infection in chicken cells.
AB  - Avian leukemia subgroup J (ALV-J) is one of the most detrimental neoplastic
      diseases in poultry production. However, the differences between somatic cells
      and immune cells post-infection remain poorly understood. The aim of our study
      was to detect the different responses in chicken to infection with ALV-J in
      different cell lines. In this study, we detected transcriptome expression changes
      during infection with ALV-J in chicken embryo fibroblast (CEF) and HD11 cell
      lines. RNA-Seq was used to determine the expression levels of mRNA transcripts
      from the two cell types after infection with ALV-J at 1, 4, and 7 dpi, and gene
      ontology analyses were used to cluster differentially expressed genes into
      pathways. Quantitative real-time PCR confirmed the expression of 336 and 269
      differentially expressed genes in CEF and HD11 lines, respectively, involved in
      innate immunity (OASL, CCL4), adaptive immunity (LYZ, CD72), apoptosis and
      autophagy (WISP2, COMP), inflammation (JSC, IL8), and tumorgenesis (PCNA, GPX3).
      The notable signal transduction pathways included the PPARs signaling pathway and
      ECM-receptor interactions in CEF, and the Toll-like receptor, NOD-like receptor,
      and RIG-I-like receptor signaling pathways in HD11. To our knowledge, this is the
      first study to use high-throughput sequencing methods to investigate viral
      infection in different cell types. The results of the present study form a
      foundation for developing potential biological markers for viral infection.

PMID- 29197032
TI  - miR-221 modulates skeletal muscle satellite cells proliferation and
      differentiation.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, which play
      important roles in animals by targeting mRNA transcripts for translational
      repression. Many recent studies have shown that miRNAs are involved in the
      control of muscle development. In this study, the expression levels of miR-221 in
      different tissues and during rabbit skeletal muscle satellite cells (SMSCs)
      differentiation were detected. Gene ontology term enrichment was used to predict
      the potential biological roles of miR-221. A synthetic miR-221 mimic and a miR
      221 inhibitor were used to investigate the functions of miR-221 during SMSCs
      proliferation and differentiation to further verify the functions of miR-221 in
      muscle development. In this report, we compared the expression levels of miR-221
      in different tissues. The expression levels of miR-221 were upregulated after the
      induction of differentiation, and then were gradually downregulated during SMSCs
      differentiation. Overexpression of miR-221 promoted SMSCs proliferation, whereas
      inhibiting expression restrained proliferation in the EdU and CCK-8 assays. In
      addition, overexpression of miR-221 led to a decline in the expression levels of
      the differentiation marker genes MyoG and MHC. miR-221 overexpression suppressed
      SMSCs myotube formation. On the contrary, inhibition of miR-221 promoted myotube
      formation. Our data showed that miR-221 increased SMSCs proliferation and
      decreased differentiation.

PMID- 29197031
TI  - Preclinical evaluation of the Aurora kinase inhibitors AMG 900, AZD1152-HQPA, and
      MK-5108 on SW-872 and 93T449 human liposarcoma cells.
AB  - Liposarcoma is a malignant soft tissue tumor that originates from adipose tissue
      and is one of the most frequently diagnosed soft tissue sarcomas in humans. There
      is great interest in identifying novel chemotherapeutic options for treating
      liposarcoma based upon molecular alterations in the cancer cells. The Aurora
      kinases have been identified as promising chemotherapeutic targets based on their
      altered expression in many human cancers and cellular roles in mitosis and
      cytokinesis. In this study, we investigated the effects of an Aurora kinase A
      inhibitor (MK-5108), an Aurora kinase B inhibitor (AZD1152-HQPA), and a pan
      Aurora kinase inhibitor (AMG 900) on undifferentiated SW-872 and well
      differentiated 93T449 human liposarcoma cells. Treatment of the SW-872 and 93T449
      cells with MK-5108 (0-1000 nM), AZD1152-HQPA (0-1000 nM), and AMG 900 (0-1000 nM)
      for 72 h resulted in a dose-dependent decrease in the total viable cell number.
      Based upon the EC50 values, the potency of the three Aurora kinase inhibitors in
      the SW-872 cells was as follows: AMG 900 (EC50 = 3.7 nM) > AZD1152-HQPA (EC50 =
      43.4 nM) > MK-5108 (EC50 = 309.0 nM), while the potency in the 93T449 cells was
      as follows: AMG 900 (EC50 = 6.5 nM) > AZD1152-HQPA (EC50 = 74.5 nM) > MK-5108
      (EC50 = 283.6 nM). The percentage of polyploidy after 72 h of drug treatment (0
      1000 nM) was determined by propidium iodide staining and flow cytometric
      analysis. AMG 900 caused a significant increase in polyploidy starting at 25 nM
      in the SW-872 and 93T449 cells, and AZD1152-HQPA caused a significant increase
      starting at 100 nM in the SW-872 cells and 250 nM in the 93T449 cells. The Aurora
      kinase A inhibitor MK-5108 did not significantly increase the percentage of
      polyploid cells at any of the doses tested in either cell line. The expression of
      Aurora kinase A and B was evaluated in the SW-872 cells versus differentiated
      adipocytes and human mesenchymal stem cells by real-time RT-PCR and Western blot
      analysis. Aurora kinase A and B mRNA expression was significantly increased in
      the SW-872 cells versus the differentiated adipocytes and human mesenchymal stem
      cells. Western blot analysis revealed a ~ 48 kDa immunoreactive band for Aurora
      kinase A that was not present in the differentiated adipocytes or the human
      mesenchymal stem cells. A ~ 39 kDa immunoreactive band for Aurora kinase B was
      detected in the SW-872 cells, differentiated adipocytes, and human mesenchymal
      stem cells. A smaller immunoreactive band for Aurora kinase B was detected in the
      SW-872 cells but not in the differentiated adipocytes and human mesenchymal stem
      cells, and this may reflect the expression of a truncated splice variant of
      Aurora kinase B that has been associated with poor patient prognosis. The 93T449
      cells demonstrated decreased expression of Aurora kinase A and B mRNA and protein
      compared to the SW-872 cells, and also expressed the truncated form of Aurora
      kinase B. The results of these in vitro studies indicate that Aurora kinase
      inhibitors should be further investigated as possible chemotherapeutic agents for
      human liposarcoma.

PMID- 29197033
TI  - Establishment and proteomic characterization of patient-derived clear cell
      sarcoma xenografts and cell lines.
AB  - Clear cell sarcoma (CCS) is an aggressive mesenchymal malignancy characterized by
      the unique chimeric EWS-ATF1 fusion gene. Patient-derived cancer models are
      essential tools for the understanding of tumorigenesis and the development of
      anti-cancer drugs; however, only a limited number of CCS cell lines exist. The
      objective of this study was to establish patient-derived CCS models. We
      established patient-derived CCS models from a 43-yr-old female patient. We
      prepared the patient-derived xenografts (PDXs) from tumor tissues obtained
      through biopsy or surgery and isolated stable cell lines from PDXs and the
      original tumor tissue. The presence of gene fusions was examined by RT-PCR, and
      Sanger sequencing. The established cell lines were characterized by short tandem
      repeat, viability, colony and spheroid formation, and invasion analyses.
      Differences in gene enrichment between the primary tumor and cell lines were
      examined by mass spectrometry and KEGG pathway analysis. The cell lines were
      maintained for more than 80 passages, and had tumorigenic characteristics such as
      colony and spheroid formation and invasion. Mass spectrometric proteome analysis
      demonstrated that the cell lines were enriched for similar but distinct molecular
      pathways, compared to those in the xenografts and original tumor tissue. Next,
      tyrosine kinase inhibitors were screened for their suppressive effects on
      viability. We found that ponatinib, vandetanib, and doxorubicin suppressed the
      growth of cell lines, and had equivalent IC50 values. Further in-depth
      investigation and understanding of drug-sensitivity mechanisms will be important
      for the clinical applications of our cell lines.

PMID- 29197035
TI  - The Association Between Apartment Layout and Depressive Symptomology among
      Hispanic/Latino Residents in Low-Income Housing: the AHOME Study.
AB  - In this study of low-income Hispanic/Latino adults living in 291 individual
      apartments in the Bronx, New York, the apartment layout was significantly
      associated with the odds of depressive symptomology. Women living in apartments
      in which the most central rooms were the living, dining, or kitchen (i.e., rooms
      commonly used for communal activities) were less likely to have depressive
      symptomology (OR = 0.44, 95% CI = 0.22-0.86) than women in apartments where the
      central rooms were lobbies or corridors, adjusting for demographics, health
      conditions, and housing and neighborhood characteristics. No statistically
      significant association was observed in men. We present the logic underlying the
      use of layout variables in this study and discuss the implications it may have
      for understanding the role of the home environment on psychological distress
      among inhabitants. The results of this study show how space syntax analysis can
      be used to better understanding disparities in the risk of depression and offer
      an additional opportunity for public health stakeholders to identify those most
      at risk for depression.

PMID- 29197034
TI  - Nutritional demands and metabolic characteristics of the DSIR-HA-1179 insect cell
      line during growth and infection with the Oryctes nudivirus.
AB  - The DSIR-HA-1179 coleopteran cell line has been identified as a susceptible and
      permissive host for the in vitro replication of the Oryctes nudivirus, which can
      be used as a biopesticide against the coconut rhinoceros beetle, pest of palms.
      The major challenge to in vitro large-scale Oryctes nudivirus production is
      ensuring process economy. This rests, among other requisites, on the use of low
      cost culture media tailored to the nutritional and metabolic needs of the cell
      line, both in uninfected and infected cultures. The aim of the present study was
      to characterize the nutritional demands and the metabolic characteristics of the
      DSIR-HA-1179 cell line during growth and subsequent infection with Oryctes
      nudivirus in the TC-100 culture medium. Serum-supplementation of the culture
      medium was found to be critical for cell growth, and addition of 10% fetal bovine
      serum v/v led to a maximum viable cell density (16.8 * 105 cells ml-1) with a
      population doubling time of 4.2 d. Nutritional and metabolic characterization of
      the cell line revealed a trend of glucose and glutamine consumption but minimal
      uptake of other amino acids, negligible production of lactate and ammonia, and
      the accumulation of alanine, both before and after infection. The monitoring of
      virus production kinetics showed that the TC-100 culture medium was nutritionally
      sufficient to give a peak yield of 7.38 * 107 TCID50 ml-1 of OrNV at the 6th day
      post-infection in attached cultures of DSIR-HA-1179 cells in 25 cm2 T-flasks.
      Knowledge of the cell line's nutritional demands and virus production kinetics
      will aid in the formulation of a low-cost culture medium and better process
      design for large-scale OrNV production in future.

PMID- 29197036
TI  - Cancer genetic counseling communication with low-income Chinese immigrants.
AB  - As genetics and genomics become part of mainstream medicine, these advances have
      the potential to either reduce or exacerbate health disparities. Relatively,
      little research has explored the quality of genetic counseling communication
      experienced by limited English proficiency patients, especially Chinese
      Americans. We observed and audio recorded genetic counseling appointments (n =
      40) of low-income, limited English-proficient Chinese patients (n = 25) and
      conducted post-visit interviews (n = 17) using stimulated recall to examine
      patient understanding of the communication. Standard techniques based in grounded
      theory, including iterative data review and multiple coders, were used to analyze
      observation fieldnotes and interview transcripts and to identify these themes:
      (1) strong beliefs in environmental causes of cancer and skepticism about genetic
      causes, (2) willingness to undergo genetic testing despite skepticism of
      hereditary cause of cancer, (3) misunderstanding of key information needed to
      make informed decisions about testing and screening/prevention options, (4)
      variable quality of medical interpretation, and (5) selective family
      communication about cancer and genetic counseling and testing. Together, these
      themes describe substantial gaps in communication and identify the need for
      genetic counseling techniques and skills that enable counselors to communicate
      more effectively across language, literacy, and culture. Understanding the
      mechanisms of inheritance and the implications of genetic test results can be
      challenging for anyone, and it is exceptionally daunting for those who have
      limited English proficiency and/or low literacy. For Chinese immigrant patients
      to reap the full benefits of genetic counseling and testing, effective
      communication is essential. Research on interventions to improve communication is
      needed to ensure that disparities do not widen as genomic medicine reaches a more
      diverse population.

PMID- 29197037
TI  - Respiratory response of grass carp Ctenopharyngodon idellus to dissolved oxygen
      changes at three acclimation temperatures.
AB  - Respiratory parameters of grass carp were studied during dissolved oxygen (DO)
      changes from normal DO to hypoxia, then return to normal DO at 15, 25, and 30 
      degrees C acclimation, respectively. The results showed that with increases of
      acclimation temperature at normoxia the respiratory frequency (fR), oxygen
      consumption rate (VO2), respiratory stroke volume (VS.R), gill ventilation (VG),
      and VG/VO2 of grass carp increased significantly, but the oxygen extraction
      efficiency (EO2) of fish decreased significantly (P < 0.05). With declines of DO
      levels, the fR, VS.R, VG, and VG/VO2 of fish increased significantly at different
      acclimation temperatures (P < 0.05). A slight increase was found in VO2, and the
      EO2 of fish remained almost constant above DO levels of 3.09, 2.91, and 2.54 mg l
      1 at 15, 25, and 30  degrees C, while the VO2 and EO2 began to decrease
      significantly with further reductions in DO levels (P < 0.05). After 0.5 h of
      recovery to normoxia from hypoxia at three acclimation, the fR, VS.R, VG, and
      VG/VO2 of the fish decreased sharply; meanwhile, the VO2 and EO2 increased
      sharply (P < 0.05). The respiratory parameters of fish gradually approached
      initial values with prolonged recovery time to normoxia, and reached their
      initial values in 2.5 h at 25 and 30  degrees C acclimation. The critical oxygen
      concentrations (Cc) of fish for VO2 were 2.42 mg l-1 at 15  degrees C, 2.02 mg l
      1 at 25  degrees C, and 1.84 mg l-1 at 30  degrees C, respectively. The results
      suggest that grass carp are highly adapted to varied DO and short-term hypoxia
      environments.

PMID- 29197039
TI  - Correction to: Insights on dispersal and recruitment paradigms: sex- and age
      dependent variations in a nomadic breeder.
AB  - Unfortunately, Table 1 was incorrectly.

PMID- 29197038
TI  - Barbed versus traditional suture for enterotomy closure after laparoscopic right
      colectomy with intracorporeal mechanical anastomosis: a case-control study.
AB  - Our aim was to establish the safety and efficacy of barbed suture for enterotomy
      closure after laparoscopic right colectomy with intracorporeal anastomosis. This
      study included 47 patients who underwent laparoscopic right hemicolectomy with
      intracorporeal mechanical anastomosis and barbed suture enterotomy closure
      (barbed suture closure-BSC) for adenocarcinoma (with the exception of T4 lesions
      and metastasis), compared with 47 matched patients who underwent laparoscopic
      right hemicolectomy with intracorporeal mechanical anastomosis and conventional
      suture enterotomy closure (conventional suture closure-CSC) during the same
      period. Controls were matched for stage, age, and gender via a statistically
      generated selection of all laparoscopic right hemicolectomies performed from
      January 2009 until December 2015. There was no difference between the two groups
      in terms of age, sex, BMI, ASA, co-morbidity, previous abdominal surgery, cancer
      site and cancer staging. In terms of operating time (median 120 min for BSC and
      127.5 min for CSC), histopathological results, surgical site complications (2.1%
      for BSC and 8.5% for CSC), hospitalization (median 6 days for BSC and 5 days for
      CSC), readmission rate (0%), there were no differences between the groups (p >
      0.05). No significant differences were noted between the two groups in terms of
      the postoperative course. Our results support that the use of knotless barbed
      sutures for enterotomy closure after laparoscopic right colectomy with
      intracorporeal mechanical anastomosis is safe and reproducible.

PMID- 29197040
TI  - Phenotypic plasticity and climate change: can polar bears respond to longer
      Arctic summers with an adaptive fast?
AB  - Plasticity in the physiological and behavioural responses of animals to prolonged
      food shortages may determine the persistence of species under climate warming.
      This is particularly applicable for species that can "adaptively fast" by
      conserving protein to protect organ function while catabolizing endogenous
      tissues. Some Ursids, including polar bears (Ursus maritimus), adaptively fast
      during winter hibernation-and it has been suggested that polar bears also employ
      this strategy during summer. We captured 57 adult female polar bears in the
      Southern Beaufort Sea (SBS) during summer 2008 and 2009 and measured blood
      variables that indicate feeding, regular fasting, and adaptive fasting. We also
      assessed tissue delta13C and delta15N to infer diet, and body condition via mass
      and length. We found that bears on shore maintained lipid and protein stores by
      scavenging on bowhead whale (Balaena mysticetus) carcasses from human harvest,
      while those that followed the retreating sea ice beyond the continental shelf
      were food deprived. They had low ratios of blood urea to creatinine (U:C),
      normally associated with adaptive fasting. However, they also exhibited low
      albumin and glucose (indicative of protein loss) and elevated alanine
      aminotransferase and ghrelin (which fall during adaptive fasting). Thus, the ~
      70% of the SBS subpopulation that spends summer on the ice experiences more of a
      regular, rather than adaptive, fast. This fast will lengthen as summer ice
      declines. The resulting protein loss prior to winter could be a mechanism driving
      the reported correlation between summer ice and polar bear reproduction and
      survival in the SBS.

PMID- 29197041
TI  - Giving predators a wide berth: quantifying behavioral predator shadows in
      colonizing aquatic beetles.
AB  - The perceived quality of habitat patches in complex landscapes is highly context
      dependent. Characteristics of neighboring patches in such complex landscapes can
      influence perceived habitat quality, altering colonization dynamics and community
      structure. Spatial contagion of predation risk across patches has been observed
      over smaller spatial scales in aquatic systems. Naturally colonizing aquatic
      beetles were used to examine the spatial dynamics of risk contagion by
      quantifying the size of predator shadows around fish patches across spatial
      scales potentially involving numerous patches in natural landscapes. These
      consisted of fish free, replicate experimental mesocosm arrays radiating from
      larger central mesocosms containing fish, and allowed examination of the effect
      of distance to fish on beetle abundance, rarified species richness, and variation
      in species responses. Overall, beetles avoided pools closer to fish, but species
      varied in colonization pattern, resulting in species-specific predator shadows
      and potential behavioral species sorting. The spatial and phylogenetic extent of
      contagion and other context-dependent effects has implications for the role of
      complex behavior in the dynamics of communities and metacommunities.

PMID- 29197042
TI  - In Reply: Vitamin D Status May Explain Some of the Racial Disparities in Rectal
      Cancer.

PMID- 29197043
TI  - Questions About In-Breast Tumor Recurrence in Patients Treated with Breast
      Conserving Therapy.

PMID- 29197044
TI  - Intraoperative Ultrasound-Guided Excision of Axillary Clip in Patients with Node
      Positive Breast Cancer Treated with Neoadjuvant Therapy (ILINA Trial) : A New
      Tool to Guide the Excision of the Clipped Node After Neoadjuvant Treatment.
AB  - BACKGROUND: The accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant
      therapy (NAT) has been improved with the placement of a clip in the positive node
      prior to treatment. Several methods have been described for clipped node excision
      during SLNB after NAT. We assessed the feasibility of intraoperative ultrasound
      (IOUS)-guided excision of the clipped node during SLNB and investigated whether
      the accuracy of SLNB is improved. METHODS: After approval by the Institutional
      Ethics Committee, all breast cancer patients undergoing NAT had an US-visible
      clip placed in the positive node. The ILINA trial consisted of IOUS-guided
      excision of the clipped node along with SLNB and axillary lymph node dissection
      (ALND). RESULTS: Forty-six patients had a clip placed in the positive node. In
      two (4.3%) cases, the clip could not be seen prior to surgery and the patient
      underwent ALND; however, the clipped node was successfully removed by IOUS-guided
      excision in 44 patients. Thirty-five patients (79.5%) underwent SLNB along with
      IOUS-guided excision of the clipped node and ALND, and were subsequently included
      in the ILINA trial. Nine patients were not included (five patients with SLNB only
      and four patients with ALND without SLNB). SLNB matched the clipped node in 27
      (77%) patients. The false negative rate for the ILINA protocol was 4.1% (95%
      confidence interval 0.1-21.1%). CONCLUSIONS: IOUS-guided excision of the axillary
      clipped node after NAT was feasible, safe, and successful in 100% of cases. The
      ILINA trial is accurate in predicting axillary nodal status after NAT.

PMID- 29197045
TI  - Shift Towards Older Bariatric Patients.

PMID- 29197046
TI  - Evaluation of Nutritional Status Post Laparoscopic Sleeve Gastrectomy-5-Year
      Outcomes.
AB  - INTRODUCTION: Obesity is considered a public health problem and has led to
      advancements in bariatric surgery. Laparoscopic sleeve gastrectomy (LSG) had
      become the most performed procedure worldwide; however, its consequences on
      nutritional status in the short and long term are of concern. METHODS: A
      retrospective analysis of medical records and bariatric database of patients who
      underwent LSG from October 2008-September 2015 at Al-Amiri Hospital, Kuwait, was
      performed. Data regarding nutritional status along with demographic data were
      collected over a 5-year follow-up period. RESULTS: One thousand seven hundred
      ninety-three patients comprising of 74% females and 26% males were included. The
      greatest % total body weight loss (%TBWL) was at 18 months post-LSG (33%),
      corresponding to a % excess weight loss (%EWL) of 73.8%. With regard to
      nutritional status, vitamin B1 showed a significant drop at 3-5 years post-op in
      comparison to pre-op value, but stayed within the normal range throughout the
      study. Red blood cells count, hemoglobin, and hematocrit also showed a
      significant drop starting from 6 months post-op until the fifth year of follow
      up. On the other hand, vitamins B6 and B12 showed a significant increase at 6
      months post-op and decreased afterwards, but did not reach pre-op values. Vitamin
      D also showed a significant increase throughout the study period from deficient
      value at the pre-op time, but remained insufficient. Albumin, transferrin,
      folate, ferritin, iron, and vitamin B2 showed no significant changes at 5 years
      post-LSG compared to pre-op values. CONCLUSION: Little is known about the
      nutritional status and optimal nutritional care plan post-LSG, especially in the
      longer term. Nutritional deficiencies were prevalent prior and post-LSG. Some of
      the nutritional parameters improved and even reached the abnormal high level post
      LSG. These observations highlight the importance of pre- and post-operative
      nutritional assessment and tailored supplementation to ensure optimal nutritional
      status.

PMID- 29197047
TI  - Correction to: Long-Term (over 10 Years) Retrospective Follow-up of Laparoscopic
      Adjustable Gastric Banding.
AB  - In the original article the spelling of author Naama Kafri was incorrect.

PMID- 29197049
TI  - Similar Helicobacter pylori Eradication Rate in Obese Patients Undergoing Gastric
      Bypass Surgery and in General Population.

PMID- 29197048
TI  - Contraception, Menstruation, and Sexuality after Bariatric Surgery: a Prospective
      Cohort Study.
AB  - BACKGROUND: Women with a history of bariatric surgery are recommended to avoid
      pregnancy at least 12 months after surgery. Evidence on the impact of bariatric
      surgery on contraception, menstrual cycle, and sexuality in the first year
      postoperative is therefore indispensable. OBJECTIVES: The objective of this paper
      is to prospectively study changes in contraception, menstrual cycle and sexuality
      in women of reproductive age following bariatric surgery. SETTING: The study was
      conducted in two secondary medical centers and a tertiary academic medical
      center. METHODS: Women attending for bariatric surgery or who recently underwent
      bariatric surgery completed online questionnaires about contraception, menstrual
      cycle, and sexual behavior before surgery and 6 and 12 months after surgery.
      RESULTS: The study included data from 71 women, including 70 and 47 women at 6
      and 12 months after bariatric surgery, respectively. Preoperatively, 43.6% (n =
      31/71) used a short-acting hormonal contraceptive, the usage of which decreased
      significantly to, respectively, 32.8% (n = 23/70; p = .031) and 27.7% (n = 13/47;
      p = .022) 6 and 12 months post-surgery. Usage of long-acting contraceptive
      methods increased from 26.7% (n = 19/71) preoperatively to 38.6% (n = 27/70; p =
      .021) and 42.6% (n = 20/47; p = .004) at 6 and 12 months. Combined oral
      contraceptives (COC) remained used (39.4% preoperatively, 27.1 and 14.9% at 6 and
      12 months postoperatively). Menstrual cycle (frequency, pattern, duration of the
      cycle, and the menstruation itself) and sexual behavior (intimate relationship,
      frequency of intercourse, and satisfaction) did not differ significantly before
      and after surgery. CONCLUSIONS: Women undergoing bariatric surgery appear to
      switch their type of contraceptive from oral, short-acting hormonal
      contraceptives to non-oral, long-acting contraceptives. No changes in menstrual
      cycle and sexual behavior were shown.

PMID- 29197050
TI  - The common rate control account of prediction motion.
AB  - In prediction-motion (PM) tasks, people judge the current position of an occluded
      moving object. People can also judge the current number on an occluded digital
      counter or the current colour of an occluded colour-change display. These
      abilities imply that we can run mental simulations at a chosen speed, even
      without feedback from the senses. There is increasing evidence that the brain has
      a common rate control module for pacing all such dynamic mental simulations. The
      common rate control account of PM has more explanatory power than alternative
      accounts which emphasise the role of mental imagery or the oculomotor system.
      Finally, neuroimaging work suggests that the common rate controller is a part of
      a core timing network that incorporates basal ganglia circuitry.

PMID- 29197051
TI  - Environmental sound priming: Does negation modify N400 cross-modal priming
      effects?
AB  - Human information processing is incredibly fast and flexible. In order to
      survive, the human brain has to integrate information from various sources and to
      derive a coherent interpretation, ideally leading to adequate behavior. In
      experimental setups, such integration phenomena are often investigated in terms
      of cross-modal association effects. Interestingly, to date, most of these cross
      modal association effects using linguistic stimuli have shown that single words
      can influence the processing of non-linguistic stimuli, and vice versa. In the
      present study, we were particularly interested in how far linguistic input beyond
      single words influences the processing of non-linguistic stimuli; in our case,
      environmental sounds. Participants read sentences either in an affirmative or
      negated version: for example: "The dog does (not) bark". Subsequently,
      participants listened to a sound either matching or mismatching the affirmative
      version of the sentence ('woof' vs. 'meow', respectively). In line with previous
      studies, we found a clear N400-like effect during sound perception following
      affirmative sentences. Interestingly, this effect was identically present
      following negated sentences, and the negation operator did not modulate the cross
      modal association effect observed between the content words of the sentence and
      the sound. In summary, these results suggest that negation is not incorporated
      during information processing in a manner that word-sound association effects
      would be influenced.

PMID- 29197052
TI  - Correction to: Adaptation in toxic environments: comparative genomics of loci
      carrying antibiotic resistance genes derived from acid mine drainage waters.
AB  - The original version of this article unfortunately contains a mistake.

PMID- 29197053
TI  - Film-forming ability of collagen hydrolysate extracted from leather solid wastes
      with chitosan.
AB  - Discharges of huge quantities of leather solid wastes by leather industries and
      the increased use of synthetic packaging films have raised serious concerns on
      account of their environmental impacts. The paper focuses on the development and
      characterization of potential environmentally friendly composite films using
      collagen hydrolysate (CH) extracted from leather solid wastes and chitosan (C) to
      assess the feasibility of producing polymeric materials suitable for applications
      in packaging and wrapping purposes. Solid collagen-based protein hydrolysate was
      extracted from chromium-tanned leather wastes and analyzed to determine its
      chemical properties. With the goal of improving the physico-chemical performance
      of CH, three types of composite films (CH75/C25, CH50/C50, CH25/C75) were
      prepared with increasing concentrations of C, and some of their physical and
      functional properties were characterized. The results indicated that the addition
      of C caused increase (p < 0.05) in the thickness, tensile strength (TS),
      elasticity modulus (EM), and water vapor permeability (WVP), leading to stronger
      films as compared with CH film, but significantly (p < 0.05) decreased the
      elongation at break (EAB) and solubility of films (p < 0.05). The light barrier
      measurements present low values of transparency at 600 nm of the CH/C films,
      indicating that the films are very transparent and they have excellent barrier
      properties against UV light. The structural properties investigated by FTIR and
      DSC showed total miscibility between both polymers. Scanning electron micrographs
      revealed that CH/C composite films showed a compact homogeneous structure. These
      results demonstrate the potential application of CH/C composite films in
      packaging industry.

PMID- 29197054
TI  - Joint toxicity of six common heavy metals to Chlorella pyrenoidosa.
AB  - Six common heavy metals (Ni, Fe, Zn, Pb, Cd, and Cr) in the water environment
      were selected to present five groups of binary mixture systems (Ni-Fe, Ni-Zn, Ni
      Pb, Ni-Cd, and Ni-Cr) through a direct equipartition ray design. Microplate
      toxicity analysis based on Chlorella pyrenoidosa measured the 96-h joint
      toxicities of the binary mixtures. Toxicity interaction of the binary mixture was
      analyzed by comparing the observed toxicity data with the reference model
      (concentration addition). The results indicated that Ni-Fe, Ni-Pb, and Ni-Cr
      mixtures showed additive effects at concentration tested. It was indicated that
      Ni-Zn and Ni-Cd mixtures presented additive effects at low concentrations whereas
      synergistic effects were seen at high concentrations.

PMID- 29197055
TI  - Synthesis of Co3O4-Bi2O3 using microwave-assisted method as the peroxymonosulfate
      activator for elimination of bisphenol A.
AB  - In this work, Co3O4-Bi2O3 was successfully synthesized using a microwave-assisted
      method [Co3O4-Bi2O3(MW)] and employed as a peroxymonosulfate (PMS) activator for
      bisphenol A removal. A reference catalyst was prepared using the same preparation
      conditions but different heating mode and labeled as Co3O4-Bi2O3(CH). The series
      of Co3O4-Bi2O3 was characterized using XRD, SEM, and N2 adsorption to detect
      their crystallinity, morphology, and surface area, among others. Results
      indicated that both microwave and calcination significantly affected the
      characteristic and catalytic activity of the catalyst. Moreover, the microwave
      irradiated catalyst calcined at 300  degrees C showed higher catalytic activity
      and mineralization percentage for BPA degradation than the conventionally heated
      catalyst calcined at the same temperature. Microwave temperature and microwave
      time of the proposed microwave-assisted method were also investigated. Compared
      with other catalysts, the present catalyst showed considerably superior
      preparation time and degradation efficiency. This study broadens a new horizon
      for advanced oxidation process using a PMS activator.

PMID- 29197056
TI  - Current state of yusho and prospects for therapeutic strategies.
AB  - The mass food poisoning incident yusho occurred in Japan in 1968. It was caused
      by the ingestion of rice bran oil contaminated with polychlorinated biphenyls and
      various dioxins and dioxin-like compounds including polychlorinated dibenzo-p
      dioxins and polychlorinated dibenzofurans (PCDFs). Notably, PCDFs were found to
      contribute to approximately 65% of the total toxicity equivalent in the blood of
      yusho patients. Lipophilic dioxins are retained in the body for a longer period
      than previously estimated. Victims suffered from characteristic skin
      manifestations associated with non-specific systemic symptoms, neurological
      symptoms, and respiratory symptoms. The severe symptoms seen in the initial phase
      subsequently faded, but recently, improvements have scarcely been observed. The
      Yusho Group has been researching treatments for this condition. Several clinical
      trials with chelating agents or dietary fibers aimed at accelerating the
      excretion of compounds. While some treatments increased dioxin excretion, none
      provided satisfactory symptom relief. Concurrently, various phytochemicals and
      herbal extracts have been found to possess biological activities that suppress
      dioxin-induced toxicity via aryl hydrocarbon receptor or activate the antioxidant
      nuclear factor-erythroid 2-related factor-2 (NRF2) signal pathway, making them
      promising therapeutic candidates. Here, we summarize the current status of yusho
      and findings of clinical trials for yusho patients and discuss the treatment
      prospects.

PMID- 29197057
TI  - Extracellular polymeric substances with metal adsorption capacity produced by
      Pseudoalteromonas sp. MER144 from Antarctic seawater.
AB  - The EPS-producing Pseudoalteromonas sp. MER144 was selected among 606 isolates
      from Antarctic seawater due to its evident slimy appearance on agar plates. The
      production of EPSs was enhanced by a step-by-step approach varying the carbon
      source, substrate and NaCl concentrations, temperature, and pH. Optimal
      conditions for the EPS production resulted at temperature of 4  degrees C and pH
      7, with addition of 2% sucrose (w/v) and 3% NaCl (w/v). EPSs produced under
      optimal conditions were chemically characterized, resulting in a moderate
      carbohydrate content (35%), uronic acids (14%), and proteins (12%).
      Monosaccharide composition was estimated to be Glu:Man:GluN:Ara:GluA:GalA:Gal
      (1:0.36:0.26:0.06:0.06:0.05:0.03), while the estimated molecular weight was about
      250 kDa. The addition of sucrose in the culture medium, by stimulating the EPS
      production, allowed MER144 to tolerate higher concentrations of mercury and
      cadmium. This finding was probably dependent on the presence of uronic acids and
      sulfate groups, which can bind cations, in the extracted EPSs. Monitoring EPS
      production under optimal conditions at different concentrations of mercury and
      cadmium revealed that EPS amounts increased at increasing heavy metal
      concentrations, indicating an adaptation to the stress conditions tested.

PMID- 29197058
TI  - Thiamethoxam induced hepatotoxicity and pro-carcinogenicity in rabbits via
      motivation of oxidative stress, inflammation, and anti-apoptotic pathway.
AB  - Thiamethoxam (TMX) is a non-mutagenic neonicotinoid insecticide that is widely
      used to combat different types of insects. The hepatotoxicity and carcinogenicity
      of TMX have been approved previously in mice but not in rats. However, the TMX
      induced hepatotoxic and pro-carcinogenic effects on rabbits remain unclear. The
      present study elucidated the roles of oxidative stress, pro-inflammatory
      cytokines, and apoptosis-related genes in the hepatotoxic and carcinogenic
      effects of TMX on rabbits. Sixteen male rabbits were equally divided into two
      groups; eight rabbits orally treated with TMX at a dose of 250 mg/kg b.w for 90
      successive days. Hepatotoxic effects of TMX were evidenced by attenuation of
      liver enzyme activities, elevation of bilirubin levels, and alterations in the
      hepatic architecture, including hepatocyte death by necrosis and apoptosis,
      lymphocyte infiltration and fibrosis. TMX induced oxidative stress, as evidenced
      by the significant increases in malondialdehyde levels and antioxidant enzyme
      (glutathione transferase and catalase) activities along with a decrease in
      glutathione levels. TMX also up-regulated the mRNA levels of interleukin-6 (1.6
      fold) and B cell lymphoma-2 (1.8-fold) and down-regulated the mRNA level of the
      tumor necrosis factor-alpha (0.8-fold), indicating its effects on cell survival
      and proliferation through the inhibition of apoptosis. Interestingly, the
      elevated level of carcinoembryonic antigen and the appearance of ground glass
      like hepatocytes suggested that TMX exerted a pro-carcinogenic effect. In
      conclusion, TMX exerts potentially hepatotoxic and pro-carcinogenic effects on
      rabbits by modulating oxidative/antioxidative status and pro-inflammatory
      cytokine production, inhibiting apoptosis and activating cell survival pathways.

PMID- 29197059
TI  - Numerical investigation of the efficiency of emission reduction and heat
      extraction in a sedimentary geothermal reservoir: a case study of the Daming
      geothermal field in China.
AB  - The utilization of geothermal energy is clean and has great potential worldwide,
      and it is important to utilize geothermal energy in a sustainable manner.
      Mathematical modeling studies of geothermal reservoirs are important as they
      evaluate and quantify the complex multi-physical effects in geothermal
      reservoirs. However, previous modeling efforts lack the study focusing on the
      emission reduction efficiency and the deformation at geothermal wellbores caused
      by geothermal water extraction/circulation. Emission efficiency is rather
      relevant in geothermal projects introduced in areas characterized by elevated air
      pollution where the utilization of geothermal energy is as an alternative to
      burning fossil fuels. Deformation at geothermal wellbores is also relevant as
      significant deformation caused by water extraction can lead to geothermal
      wellbore instability and can consequently decrease the effectiveness of the heat
      extraction process in geothermal wells. In this study, the efficiency of emission
      reduction and heat extraction in a sedimentary geothermal reservoir in Daming
      County, China, are numerically investigated based on a coupled multi-physical
      model. Relationships between the efficiency of emission reduction and heat
      extraction, deformation at geothermal well locations, and geothermal field
      parameters including well spacing, heat production rate, re-injection
      temperature, rock stiffness, and geothermal well placement patterns are analyzed.
      Results show that, although large heat production rates and low re-injection
      temperatures can lead to decreased heat production in the last 8 years of heat
      extraction, they still improve the overall heat production capacity and emission
      reduction capacity. Also, the emission reduction capacity is positively
      correlated with the heat production capacity. Deformation at geothermal wellbore
      locations is alleviated by smaller well spacing, lower heat production rates, and
      smaller numbers of injectors in the well pattern, and by placing wells at
      locations with higher rock stiffness. Compared with the reference case with coal
      burning for heating purposes, the yearly emission reduction capacity can reach 1
      * 107 kg by switching to the direct utilization of geothermal energy in Daming
      field.

PMID- 29197060
TI  - Repellency potential of essential oils against housefly, Musca domestica L.
AB  - In present study, the essential oils such as Mentha piperita (mentha oil, M.O),
      Cymbopogan citratus (lemongrass oil, LG.O), Citrus sinensis (orange oil, O.O),
      and Eucalyptus globulus (eucalyptus oil, E.O) were evaluated for repellency
      against housefly (Musca domestica) in a specially designed chamber. Further, to
      study any synergistic effect, essential oil combinations, i.e., M.O + LG.O, M.O +
      O.O, and M.O + E.O, were screened at 50:50 and 70:30 ratios. The results showed
      superior repellency of mentha and mentha + lemongrass (70:30) with RC95 value of
      0.009 MUl/cm3. The other oils and combinations showed higher values of RC95
      (0.010-0.041 MUl/cm3). The order of repellency was observed to be mentha = mentha
      + lemongrass (70:30) > mentha + lemongrass (50:50) = lemongrass = mentha + orange
      (50:50) = mentha + orange (70:30) > mentha + eucalyptus (70:30) > orange > mentha
      + eucalyptus (50:50) > eucalyptus. Chemical composition of selected essential
      oils indicated various monoterpenes as active components for efficient
      repellency. The essential oil of mentha marked the presence of menthol (38%) and
      menthone (27%) in major fractions, whereas citral (49%) was found dominating in
      lemongrass oil. Eucalyptus and orange oils showed the presence of 1,8-cineole
      (85%), and limonene (87%), respectively, as major components of oils. Further,
      monoterpenes (menthol and limonene) were also evaluated for repellency against
      housefly. The data showed 90 +/- 5 and 60 +/- 5% repellency from menthol and
      limonene, respectively, after 1 h, indicating the vital role of monoterpenes in
      overall efficacy of essential oil.

PMID- 29197061
TI  - Influence of technological and municipal wastewaters on vulnerable karst riverine
      system, Krka River in Croatia.
AB  - Exceptional natural value of karst rivers, as well as their potential as a source
      of drinking water supply, contributes to the importance of developing strict
      environmental protection. Although most of its watercourse is proclaimed national
      park, Krka River is impacted by technological and municipal wastewaters, which
      are released without proper purification only 2 km upstream of the park border.
      In order to assess water ecological status of the Krka River, vulnerability of
      karst ecosystem and potential threat to the Krka National Park, spatial and
      temporal variability of physico-chemical and microbiological water parameters, as
      well as concentrations of 25 total dissolved metals/metalloids were evaluated.
      All parameters indicated deteriorated water quality near the wastewater
      influences, which was for certain metals and bacterial counts even comparable to
      other world rivers of technological/rural catchment. Downstream location pointed
      to purification processes in karst river, although nutrients and conductivity
      were still in a range below good water quality and Al, Co, Fe, Li, Mn, Ni, Sr,
      Ti, and Zn levels remained comparable to their levels in the pollution impacted
      area, especially in autumn, indicating season-dependent processes. Presented data
      provided background status and identified pollution influences in the karst
      riverine system which indicated potential risk for protected area and a need for
      comprehensive water quality assessment.

PMID- 29197062
TI  - Clustering pesticides according to their molecular properties, fate, and effects
      by considering additional ecotoxicological parameters in the TyPol method.
AB  - Understanding the fate and ecotoxicological effects of pesticides largely depends
      on their molecular properties. We recently developed "TyPol" (Typology of
      Pollutants), a classification method of organic compounds based on statistical
      analyses. It combines several environmental (sorption coefficient, degradation
      half-life) and one ecotoxicological (bioconcentration factor) parameters, to
      structural molecular descriptors (number of atoms in the molecule, molecular
      surface, dipole moment, energy of orbitals, etc.). The present study attempts to
      extend TyPol to the ecotoxicological effects of pesticides on non-target
      organisms, based on data analysis from available literature and databases. It
      revealed that relevant ecotoxicological endpoints for terrestrial organisms
      (e.g., soil microorganisms, invertebrates) that support a range of ecosystemic
      services are lacking as compared to aquatic organisms. The availability of
      ecotoxicological parameters was also lower for chronic than for acute ecotoxicity
      endpoints. Consequently, seven parameters were included for acute (EC50, LC50)
      and chronic (NOEC) ecotoxicological effects for one terrestrial (Eisenia sp.) and
      three aquatic (Daphnia sp., algae, Lemna sp.) organisms. In this new
      configuration, we used TyPol to classify 50 pesticides into different clusters
      that gather molecules with similar environmental behaviors and ecotoxicological
      effects. The classification results evidenced relationships between molecular
      descriptors, environmental parameters, and the added ecotoxicological endpoints.
      This proof-of-concept study also showed that TyPol in silico classification can
      successfully address new scientific questions and be expanded with other
      parameters of interest.

PMID- 29197063
TI  - Indicators of environmental contamination by heavy metals in leaves of Taraxacum
      officinale in two zones of the metropolitan area of Mexico City.
AB  - The present study was designed to detect the effect of heavy metals in two zones
      of the Metropolitan Area of Mexico City (MAMC), the Centro de Ciencias de la
      Atmosfera (CCA), and the Altzomoni station in the Iztaccihuatl-Popocatepetl
      National Park. Taraxacum officinale was selected as the indicator organism of
      responses to atmospheric contamination by heavy metals. Determinations of heavy
      metals were performed, and total mRNA was extracted to quantify the expression of
      microRNA398 (miR398), superoxide dismutase 2 (CSD2), and the amounts of free
      radicals using the bromide of 3-(4,5-dimethylthiazole-2-ilo)-2,5
      diphenyltetrazole (MTT) salts reduction assay. Results from the Altzomoni station
      showed high concentrations of five heavy metals, especially Aluminum, while three
      heavy metals were identified in the CCA-UNAM zone, most importantly, Vanadium,
      both in the dry season; miR398 expression presented subtle changes but was
      greater in the leaves from the stations with higher concentrations of heavy
      metals. Observations included a significant expression of CSD2, mainly in the dry
      season in both study zones, where levels were significant with respect to
      controls (p < 0.05). Reduced MTT was also higher in the dry season than in the
      rainy season (p < 0.05). In conclusion, the increase in heavy metals on the
      leaves of Taraxacum officinale induces increased expression of the CSD2 gene and
      reduced MTT; thus, they can be used as indicators for biomonitoring heavy metal
      concentrations.

PMID- 29197064
TI  - Postnatal Subacute Benzo(a)Pyrene Exposure Caused Neurobehavioral Impairment and
      Metabolomic Changes of Cerebellum in the Early Adulthood Period of Sprague-Dawley
      Rats.
AB  - Benzo(a)pyrene (BaP) is a widespread environmental contaminant that has been
      associated with neurotoxicity in mammals. It has strong toxic effects on the
      developing central nervous system. Cerebellum is associated with locomotor
      activity and anxiety behavior, but there is very little research about the toxic
      effects of BaP in cerebellum. The present study aims to investigate the global
      influence of BaP subacute exposure on the metabolome of rat cerebellum. Male
      neonatal rats (postnatal day 5) were divided into two groups: control group and
      BaP-treated group (2 mg/kg/day for 7 weeks). Open field test and transmission
      electron microscopy were performed to analyze neurobehavior and
      ultramicrostructure alteration. Gas chromatography-mass spectrometry (GC-MS) was
      used to analyze metabolites of the cerebellum in both groups. The results
      revealed that postnatal exposure to BaP promoted pathological changes in the
      cerebellum and increased locomotor and anxiety activities in early adulthood.
      Twenty differential significant metabolites were identified by multivariate
      statistical analysis. Further metabolic pathway impact analysis and network
      analysis suggested that the primary metabolic pathways affected included pathway
      involved in energy metabolism, methionine and cysteine metabolism, and
      glutathione metabolism. These findings suggest that BaP-induced cerebellum injury
      may be correlated with metabolic changes and provide an area to target to reduce
      the negative effects of BaP.

PMID- 29197065
TI  - Exosomes from heat-stressed tumour cells inhibit tumour growth by converting
      regulatory T cells to Th17 cells via IL-6.
AB  - Exosomes derived from heat-stressed tumour cells (HS-TEXs), which contain
      abundant heat shock protein (HSP) 70, strongly induce antitumour immune
      responses. HSP70-induced interleukin (IL)-6 promotes IL-17 expression and causes
      rejection of established prostate tumours. However, it remains unclear whether HS
      TEXs exhibit antitumour effects by converting regulatory T cells (Tregs ) into T
      helper type 17 (Th17) cells. In this study, we found that compared with TEXs, HS
      TEXs were more potent in stimulating secretion of IL-6 from dendritic cells. In
      vitro, IL-6 blocked tumour cell-derived transforming growth factor beta 1-induced
      Treg differentiation and promoted Th17 cell differentiation. HS-TEXs exerted
      strong antitumour effects, converting Tregs into Th17 cells with high efficiency,
      a process that was entirely dependent upon IL-6. Neutralization of IL-17
      completely abolished the antitumour effect of TEXs, but only partially inhibited
      that of HS-TEXs. In addition, we found higher levels of IL-6 and IL-17 in serum
      from tumour patients treated with hyperthermia, and an increase in Th17 cells and
      a decrease in Tregs was detected in peripheral blood mononuclear cells isolated
      from these patients after hyperthermia. Therefore, our results demonstrate that
      HS-TEXs possess a powerful capacity to convert immunosuppressive Tregs into Th17
      cells via IL-6, which contributes to their potent antitumour effect.

PMID- 29197067
TI  - Cervical cancer screening through human papillomavirus testing in community
      health campaigns versus health facilities in rural western Kenya.
AB  - OBJECTIVE: To determine the effectiveness of community health campaigns (CHCs) as
      a strategy for human papillomavirus (HPV)-based cervical cancer screening in
      rural western Kenya. METHODS: Between January and November 2016, a cluster
      randomized trial was carried out in 12 communities in western Kenya to
      investigate high-risk HPV testing offered via self-collection to women aged 25-65
      years in CHCs versus government health facilities. Outcome measures were the
      total number of women accessing cervical cancer screening and the proportion of
      HPV-positive women accessing treatment. RESULTS: In total, 4944 women underwent
      HPV-based cervical cancer screening in CHCs (n=2898) or health facilities
      (n=2046). Screening uptake as a proportion of total eligible women in the
      population was greater in communities assigned to CHCs (60.0% vs 37.0%, P<0.001).
      Rates of treatment acquisition were low in both arms (CHCs 39.2%; health
      facilities 31.5%; P=0.408). DISCUSSION: Cervical cancer screening using HPV
      testing of self-collected samples reached a larger proportion of women when
      offered through periodic CHCs compared with health facilities. The community
      based model is a promising strategy for cervical cancer prevention. Lessons
      learned from this trial can be used to identify ways of maximizing the impact of
      such strategies through greater community participation and improved linkage to
      treatment. ClinicalTrials.gov registration: NCT02124252.

PMID- 29197066
TI  - Characterization of the properties of a selective, orally bioavailable autotaxin
      inhibitor in preclinical models of advanced stages of liver fibrosis.
AB  - BACKGROUND AND PURPOSE: Autotaxin (ATX) is a secreted phospholipase which
      hydrolyses lysophosphatidylcholine to generate lysophosphatidic acid (LPA). The
      extracellular signalling molecule LPA exerts its biological actions through
      activation of six GPCRs expressed in various cell types including fibroblasts.
      Multiple preclinical studies using knockout animals, LPA receptor antagonists or
      ATX inhibitors have provided evidence for a potential role of the ATX/LPA axis in
      tissue fibrosis. Despite growing evidence for a correlation between ATX levels
      and the degree of fibrosis in chronic liver diseases, including viral hepatitis
      and hepatocellular carcinoma, the role of ATX in non-alcoholic steatohepatitis
      (NASH) remains unclear. EXPERIMENTAL APPROACH: The relevance of ATX in the
      pathogenesis of liver fibrosis was investigated by oral administration of Ex_31,
      a selective ATX inhibitor, in a 10 week model of carbon tetrachloride-induced
      liver injury and in a 14 week model of choline-deficient amino acid-defined diet
      induced liver injury in rats. KEY RESULTS: Oral administration of Ex_31, a
      selective ATX inhibitor, at 15 mg.kg-1 twice daily in therapeutic intervention
      mode resulted in efficient ATX inhibition and more than 95% reduction in plasma
      LPA levels in both studies. Treatment with Ex_31 had no effect on biomarkers of
      liver function, inflammation, or fibrosis and did not result in histological
      improvements in diseased animals. CONCLUSIONS AND IMPLICATIONS: Our findings
      question the role of ATX in the pathogenesis of hepatic fibrosis and the
      potential of small molecule ATX inhibitors for the treatment of patients with
      NASH and advanced stages of liver fibrosis.

PMID- 29197068
TI  - Drivers of advanced stage at breast cancer diagnosis in the multicountry African
      breast cancer - disparities in outcomes (ABC-DO) study.
AB  - Breast cancer (BC) survival rates in sub-Saharan Africa (SSA) are low in part due
      to advanced stage at diagnosis. As one component of a study of the entire journey
      of SSA women with BC, we aimed to identify shared and setting-specific drivers of
      advanced stage BC. Women newly diagnosed in the multicountry African Breast
      Cancer-Disparities in Outcomes (ABC-DO) study completed a baseline interview and
      their stage information was extracted from medical records. Ordinal logistic
      regression was used to estimate odds ratios (OR) and 95% confidence intervals
      (CI) for advanced stage (I, II, III, IV) in relation to individual woman-level,
      referral and biological factors. A total of 1795 women were included from
      Nigeria, Uganda, Zambia, and the multiracial populations of Namibia and South
      Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with
      greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale).
      More advanced stage was associated with being black (4.00 (2.79, 5.74)), having
      attended <secondary education (1.75 (1.42, 2.16)), having never heard of BC (1.64
      (1.31, 2.06)), an unskilled job (1.77 (1.43, 2.20)) and pregnancy in the past 3
      years (30% of <=45 year olds) (1.63 (1.15, 2.31)), and were mediated through
      delays to diagnosis: symptom duration of >= 1 year (OR 2.47 (1.93, 3.15)). These
      findings provide further evidence that late-stage BC in SSA is largely attributed
      to modifiable factors and strategies to improve BC education and awareness in
      women and the health system should be intensified.

PMID- 29197069
TI  - Polymethoxyflavones prevent benzo[a]pyrene/dextran sodium sulfate-induced
      colorectal carcinogenesis through modulating xenobiotic metabolism and ameliorate
      autophagic defect in ICR mice.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental carcinogenic
      pollutants and they have become an important issue in food contamination. Dietary
      intake of PAHs has been recognized as a major route of human exposure. However,
      the mechanisms behind dietary PAH-induced colorectal cancer (CRC) remain unclear.
      Several studies have shown that polymethoxyflavones (PMFs) are effective in
      preventing carcinogen-induced CRC or colitis. In this study, we investigated the
      preventive effect of PMFs on benzo[a]pyrene/dextran sulfate sodium (BaP/DSS)
      induced colorectal tumorigenesis in ICR mice. We found that PMFs significantly
      prevented BaP/DSS-induced colorectal tumor formation. BaP mutagenic metabolite
      and DNA adducts were found to be reduced in colonic tissue in the PMFs-treated
      groups through the modulation of BaP metabolism. At the molecular level, the
      results of RNA-sequencing indicated that PMFs ameliorated BaP/DSS-induced
      abnormal molecular mechanism change including activated inflammation,
      downregulated anti-oxidation targets, and induced metastasis genes. The
      autophagic defect caused by BaP/DSS-induced tumorigenesis was improved by
      pretreatment with PMFs. We found BaP/DSS-induced CRC may be a Wnt/beta-catenin
      independent process. Additionally, consumption of PMFs extracts also altered the
      composition of gut microbiota and made it similar to that in the control group by
      increasing butyrate-producing probiotics and decreasing CRC-related bacteria. BaP
      in combination with DSS significantly induced colorectal tumorigenesis through
      induced DNA adduct formation, abnormal gene expression, and imbalanced gut
      microbiota composition. PMFs were a powerful preventive agent that suppressed
      BaP/DSS-induced CRC via modulating multiple pathways as well as ameliorating
      autophagic defect. These results demonstrated for the first time the
      chemopreventive efficacy and comprehensive mechanisms of dietary PMFs for
      preventing BaP/DSS-induced colorectal carcinogenesis.

PMID- 29197070
TI  - The role of oxidative stress in Friedreich's ataxia.
AB  - Oxidative stress and an increase in the levels of free radicals are important
      markers associated with several pathologies, including Alzheimer's disease,
      cancer and diabetes. Friedreich's ataxia (FRDA) is an excellent paradigmatic
      example of a disease in which oxidative stress plays an important, albeit
      incompletely understood, role. FRDA is a rare genetic neurodegenerative disease
      that involves the partial silencing of frataxin, a small mitochondrial protein
      that was completely overlooked before being linked to FRDA. More than 20 years
      later, we now know how important this protein is in terms of being an essential
      and vital part of the machinery that produces iron-sulfur clusters in the cell.
      In this review, we revisit the most important steps that have brought us to our
      current understanding of the function of frataxin and its role in disease. We
      discuss the current hypotheses on the role of oxidative stress in FRDA and review
      some of the existing animal and cellular models. We also evaluate new techniques
      that can assist in the study of the disease mechanisms, as well as in our
      understanding of the interplay between primary and secondary phenotypes.

PMID- 29197071
TI  - Peroxisome proliferator-activated receptor gamma agonists for preventing
      recurrent stroke and other vascular events in people with stroke or transient
      ischaemic attack.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-gamma)
      agonists are insulin-sensitising drugs used for the treatment of insulin
      resistance. In addition to lowering glucose in diabetes, these drugs may also
      protect against hyperlipidaemia and arteriosclerosis, which are risk factors for
      stroke. This is an update of a review first published in January 2014 and
      subsequently updated in October 2015. OBJECTIVES: To assess the efficacy and
      safety of PPAR-gamma agonists in the secondary prevention of stroke and related
      vascular events for people with stroke or transient ischaemic attack (TIA).
      SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (16 May
      2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue
      5), MEDLINE (1949 to 16 May 2017), Embase (1980 to 16 May 2017), CINAHL (1982 to
      16 May 2017), AMED (1985 to 16 May 2017), and 11 Chinese databases (16 May 2017).
      In an effort to identify further published, unpublished, and ongoing trials, we
      searched ongoing trials registers, reference lists, and relevant conference
      proceedings, and contacted authors and pharmaceutical companies. We did not
      impose any language restrictions. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) evaluating PPAR-gamma agonists versus placebo for the
      secondary prevention of stroke and related vascular events in people with stroke
      or TIA, with the outcomes of recurrent stroke, vascular events, and adverse
      events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened
      the titles and abstracts of identified records, selected studies for inclusion,
      extracted eligible data, cross-checked the data for accuracy, and assessed
      methodological quality and risk of bias. We evaluated the quality of evidence for
      each outcome using the GRADE approach. MAIN RESULTS: We identified five RCTs with
      5039 participants; two studies had a low risk of bias for all domains. Four
      studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone.
      The participants in different studies were heterogeneous.Recurrent strokeThree
      studies evaluated the number of participants with recurrent stroke (4979
      participants, a single study contributing 3876 of these). Peroxisome proliferator
      activated receptor gamma agonists probably reduce the recurrence of stroke
      compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to
      0.99; moderate-quality evidence).Adverse eventsEvidence that adverse events
      occurred more frequently in participants treated with PPAR-gamma agonists when
      compared with placebo was uncertain due to wide confidence interval and high
      levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low
      quality evidence).Data were available on additional composite outcomes reflecting
      serious vascular events (all-cause death and other major vascular events; all
      cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one
      study in 984 people. This study provided low-quality evidence that PPAR-gamma
      agonists led to fewer events (data not meta-analysed).Vascular eventsPeroxisome
      proliferator-activated receptor gamma agonists given over a mean duration of 34.5
      months in a single trial of 984 participants may reduce serious vascular events
      expressed as a composite outcome of total events of cardiovascular death, non
      fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99;
      low-quality evidence).Other outcomesOne study in 20 people measured insulin
      sensitivity, and one study in 40 people measured the ubiquitin-proteasome
      activity in carotid plaques. Our confidence in the improvements observed with
      PPAR-gamma agonists were limited by small sample sizes and risk of bias. None of
      the studies reported the number of participants with disability due to vascular
      events or improvement in quality of life. AUTHORS' CONCLUSIONS: Peroxisome
      proliferator-activated receptor gamma agonists probably reduce recurrent stroke
      and total events of cardiovascular death, non-fatal myocardial infarction or non
      fatal stroke, and may improve insulin sensitivity and the stabilisation of
      carotid plaques. Their effects on adverse events are uncertain. Our conclusions
      should be interpreted with caution considering the small number and the quality
      of the included studies. Further well-designed, double-blind RCTs with large
      samples are required to assess the efficacy and safety of PPAR-gamma agonists in
      the secondary prevention of stroke and related vascular events in people with
      stroke or TIA.

PMID- 29197073
TI  - Annular erythematous plaques on the trunk.

PMID- 29197072
TI  - Induction of mast cell accumulation by chymase via an enzymatic activity- and
      intercellular adhesion molecule-1-dependent mechanism.
AB  - BACKGROUND AND PURPOSE: Chymase is a unique, abundant secretory product of mast
      cells and a potent chemoattractant for eosinophils, monocytes and neutrophils,
      but little is known of its influence on mast cell accumulation. EXPERIMENTAL
      APPROACH: A mouse peritoneal inflammation model, cell migration assay and
      flowcytometry analysis, were used to investigate the role of chymase in
      recruiting mast cells. KEY RESULTS: Chymase increased, by up to 5.4-fold, mast
      cell numbers in mouse peritoneum. Inhibitors of chymase, heat-inactivation of the
      enzyme, sodium cromoglycate and terfenadine, and pretreatment of mice with anti
      intercellular adhesion molecule 1, anti-L-selectin, anti-CD11a and anti-CD18
      antibodies dramatically diminished the chymase-induced increase in mast cell
      accumulation. These findings indicate that this effect of chymase is dependent on
      its enzymatic activity and activation of adhesion molecules. In addition, chymase
      provoked a significant increase in 5-HT and eotaxin release (up to 1.8- and 2.2
      fold, respectively) in mouse peritoneum. Since 5-HT, eotaxin and RANTES can
      induce marked mast cell accumulation, these indirect mechanisms may also
      contribute to chymase-induced mast cell accumulation. Moreover, chymase increased
      the trans-endothelium migration of mast cells in vitro indicating it also acts as
      a chemoattractant. CONCLUSION AND IMPLICATIONS: The finding that mast cells
      accumulate in response to chymase implies further that chymase is a major pro
      inflammatory mediator of mast cells. This effect of chymase, a major product of
      mast cell granules, suggests a novel self-amplification mechanism for mast cell
      accumulation in allergic inflammation. Mast cell stabilizers and inhibitors of
      chymase may have potential as a treatment of allergic disorders.

PMID- 29197074
TI  - Bullous pemphigoid complicated by cytomegalovirus disease as a manifestation of
      immune reconstitution inflammatory syndrome: retrospective analyses of our
      institutional cases and literature review.
AB  - BACKGROUND: Cytomegalovirus (CMV) disease induced by reactivation of latent CMV
      is a fatal viral infection that may develop in a setting of therapy with
      immunosuppressive agents. There is a clear need to clarify any clinical features
      and markers of CMV disease. OBJECTIVE: We investigated which clinical markers
      usually available in a clinical setting can predict CMV disease occurring in
      bullous pemphigoid (BP) patients receiving corticosteroids. METHOD: We described
      a BP patient with CMV disease complicated by gastrointestinal hemorrhage and
      liver dysfunction. Prompted by this patient, we retrospectively analyzed clinical
      features and laboratory findings in our institutional four BP patients and
      previously reported nine BP patients with CMV disease. We also compared these
      patients with our institutional 42 BP patients not complicated by CMV disease.
      RESULTS: High levels of anti-BP180 antibody titers associated with resistance to
      corticosteroids are a risk factor for the development of CMV disease. A reduction
      in platelet (PLT) and white blood cell (WBC) counts and an increase in alanine
      aminotransferase (ALT) levels 3-4 weeks after the initiation of corticosteroids
      are useful predictive markers for the onset of CMV disease. CONCLUSIONS: Frequent
      WBC, PLT, and ALT measurements may identify BP patients at a risk of subsequently
      developing CMV disease. Careful monitoring of CMV disease in BP refractory to
      systemic corticosteroids may reduce the risk of fatal outcomes.

PMID- 29197075
TI  - The "Batman flap": a novel technique to repair a large central glabellar defect.
AB  - BACKGROUND: Given the critical position of central glabella among the frontal,
      nasal, and supraorbital aesthetic subunits of the face, the reconstruction of
      large defects in this area represents a surgical challenge. METHODS: We describe
      a surgical technique based on a modified, curved, A-T flap to repair a large
      glabellar defect. RESULTS: Our modification is useful for large glabellar defects
      because it enables the distribution of the tension all over the reconstruction
      sides, avoiding a stressed central area and the subsequent risk of necrosis;
      functionally, it respects the eyebrows position and since the advancement is
      parallel to their major axes, it avoids the reduction of the distance between
      them. CONCLUSIONS: The "Batman flap" enables reconstructing a glabellar defect,
      with a good aesthetical result and the respect of the relevant aesthetical
      subunits.

PMID- 29197076
TI  - DNA methylation-based biological aging and cancer risk and survival: Pooled
      analysis of seven prospective studies.
AB  - The association between aging and cancer is complex. Recent studies have
      developed measures of biological aging based on DNA methylation and called them
      "age acceleration." We aimed to assess the associations of age acceleration with
      risk of and survival from seven common cancers. Seven case-control studies of DNA
      methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer
      and B-cell lymphoma nested in the Melbourne Collaborative Cohort Study were
      conducted. Cancer cases, vital status and cause of death were ascertained through
      linkage with cancer and death registries. Conditional logistic regression and Cox
      models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95%
      confidence intervals (CI) for associations of five age acceleration measures
      derived from the Human Methylation 450 K Beadchip assay with cancer risk (N =
      3,216 cases) and survival (N = 1,726 deaths), respectively. Epigenetic aging was
      associated with increased cancer risk, ranging from 4% to 9% per five-year age
      acceleration for the 5 measures considered. Heterogeneity by study was observed,
      with stronger associations for risk of kidney cancer and B-cell lymphoma. An
      associated increased risk of death following cancer diagnosis ranged from 2% to
      6% per five-year age acceleration, with no evidence of heterogeneity by cancer
      site. Cancer risk and mortality were increased by 15-30% for the fourth versus
      first quartile of age acceleration. DNA methylation-based measures of biological
      aging are associated with increased cancer risk and shorter cancer survival,
      independently of major health risk factors.

PMID- 29197078
TI  - Cardiopulmonary anomalies in incontinentia pigmenti patients.
AB  - BACKGROUND: Incontinentia pigmenti (IP) is a rare inherited genodermatosis that
      usually involves the skin, and also teeth, oral cavity, central nervous system,
      eyes, blood with eosinophilia, and rarely skeletal system, breast, heart, and
      lungs. Skin lesions usually appear early, at birth or within the first 2 weeks of
      life, with four different phases tending to follow Blaschko lines that may
      overlap. CASE REPORT: We report a rare case of a neonate with transient
      reversible pulmonary hypertension that presented at day 9 of life. She manifested
      increasing dyspnea and deterioration of respiratory dynamics with a serious
      pulmonary hypertension without a primary pulmonary disease. Hence, oxygen therapy
      at high flows and nitric oxide have been administered with an initial response,
      but, subsequently, because of the worsening of the respiratory activity, she
      underwent sildenafil and bosentan treatment with respiratory dynamics improvement
      and progressive decrease of the pulmonary pressures. CONCLUSION: In literature
      only a few cases of cardiopulmonary anomalies in IP have been described with
      different outcomes, and these rare complications are probably underestimated by
      physicians. We could suppose that microangiopathic damages may have a critical
      role in endothelial alterations, and these processes are probably shared by
      multiple organs involved in IP and rarely by lungs and heart.

PMID- 29197079
TI  - Postoperative outcomes following cardiac surgery in non-anaemic iron-replete and
      iron-deficient patients - an exploratory study.
AB  - Iron deficiency anaemia is strongly associated with poor outcomes after cardiac
      surgery. However, pre-operative non-anaemic iron deficiency (a probable anaemia
      precursor) has not been comprehensively examined in patients undergoing cardiac
      surgery, despite biological plausibility and evidence from other patient
      populations of negative effect on outcome. This exploratory retrospective cohort
      study aimed to compare an iron-deficient group of patients undergoing cardiac
      surgery with an iron-replete group. Consecutive non-anaemic patients undergoing
      elective coronary artery bypass grafting or single valve replacement in our
      institution between January 2013 and December 2015 were considered for inclusion.
      Data from a total of 277 patients were analysed, and were categorised by iron
      status and blood haemoglobin concentration into iron-deficient (n = 109) and iron
      replete (n = 168) groups. Compared with the iron-replete group, patients in the
      iron-deficient group were more likely to be female (43% vs. 12%, iron-replete,
      respectively); older, mean (SD) age 64.4 (9.7) vs. 63.2 (10.3) years; and to have
      a higher pre-operative EuroSCORE (median IQR [range]) 3 (2-5 [0-10]) vs. 3 (2-4
      [0-9]), with a lower preoperative haemoglobin of 141.6 (11.6) vs. 148.3 (11.7)
      g.l-1 . Univariate analysis suggested that iron-deficient patients had a longer
      hospital length of stay (7 (6-9 [2-40]) vs. 7 (5-8 [4-23]) days; p = 0.013) and
      fewer days alive and out of hospital at postoperative day 90 (83 (80-84 [0-87])
      vs. 83 (81-85 [34-86]), p = 0.009). There was no evidence of an association
      between iron deficiency and either lower nadir haemoglobin or higher requirement
      for blood products during inpatient stay. After adjusting the model for pre
      operative age, sex, renal function, EuroSCORE and haemoglobin, the mean increase
      in hospital length of stay in the iron-deficient group relative to the iron
      replete group was 0.86 days (bootstrapped 95%CI -0.37 to 2.22, p = 0.098). This
      exploratory study suggests there is weak evidence of an association between non
      anaemic iron deficiency and outcome after cardiac surgery after controlling for
      potentially confounding variables.

PMID- 29197080
TI  - Determination of the optimal programmed intermittent epidural bolus volume of
      bupivacaine 0.0625% with fentanyl 2 MUg.ml-1 at a fixed interval of forty
      minutes: a biased coin up-and-down sequential allocation trial.
AB  - The optimum time interval for 10 ml boluses of bupivacaine 0.0625% + fentanyl 2
      MUg.ml-1 as part of a programmed intermittent epidural bolus regimen has been
      found to be 40 min. This regimen was shown to be effective without the use of
      supplementary patient-controlled epidural analgesia boluses in 90% of women
      during the first stage of labour, although with a rate of sensory block to ice
      above T6 in 34% of women. We aimed to determine the optimum programmed
      intermittent epidural bolus volume at a 40 min interval to provide effective
      analgesia in 90% of women (EV90 ) during the first stage of labour, without the
      use of patient-controlled epidural analgesia. We performed a prospective double
      blind dose-finding study using the biased coin up-and-down sequential allocation
      method in 40 women. The estimated EV90 was 11.0 (95%CI 10.0-11.7) ml with the
      isotonic regression method and 10.7 (95%CI 10.3-11.0) ml with the truncated Dixon
      and Mood method. Overall, 18 women had a sensory block above T6, and 37 women
      exhibited no motor block. No women required treatment for hypotension. In
      conclusion, it is not possible to reduce the programmed intermittent epidural
      bolus volume from 10 ml, used in our current regimen, without compromising the
      quality of analgesia. Using this regimen, a high proportion of women will develop
      a sensory block above T6.

PMID- 29197077
TI  - Coevolving MAPK and PID phosphosites indicate an ancient environmental control of
      PIN auxin transporters in land plants.
AB  - Plant growth flexibly adapts to environmental conditions, implying cross-talk
      between environmental signalling and developmental regulation. Here, we show that
      the PIN auxin efflux carrier family possesses three highly conserved putative
      mitogen-activated protein kinase (MAPK) sites adjacent to the phosphorylation
      sites of the well-characterised AGC kinase PINOID, which regulates the polar
      localisation of PINs and directional auxin transport, thereby underpinning organ
      growth. The conserved sites of PIN1 are phosphorylated in vitro by two
      environmentally activated MAPKs, MPK4 and MPK6. In contrast to AGC kinases, MAPK
      mediated phosphorylation of PIN1 at adjacent sites leads to a partial loss of the
      plasma membrane localisation of PIN1. MAPK-mediated modulation of PIN trafficking
      may participate in environmental adjustment of plant growth.

PMID- 29197081
TI  - Clinical and Regulatory Aspects of Companion Diagnostic Development in Oncology.
AB  - Nearly 20 years have passed since the US Food and Drug Administration (FDA)
      approved the first companion diagnostic and today this type of assay governs the
      use of 21 different anticancer drugs. The regulators deem these assays essential
      for the safe and effective use of a corresponding therapeutic product. The
      companion diagnostic assays are important both during the drug development
      process as well as essential treatment decision tools after the approval of the
      drugs.

PMID- 29197082
TI  - Pupylation of PafA or Pup inhibits components of the Pup-Proteasome System.
AB  - The pupylation of cellular proteins plays a crucial role in the degradation
      cascade via the Pup-Proteasome system (PPS). It is essential for the survival of
      Mycobacterium smegmatis under nutrient starvation and, as such, the activity of
      many components of the pathway is tightly regulated. Here, we show that Pup, like
      ubiquitin, can form polyPup chains primarily through K61 and that this form of
      Pup inhibits the ATPase-mediated turnover of pupylated substrates by the 20S
      proteasome. Similarly, the autopupylation of PafA (the sole Pup ligase found in
      mycobacteria) inhibits its own enzyme activity; hence, pupylation of PafA may act
      as a negative feedback mechanism to prevent substrate pupylation under specific
      cellular conditions.

PMID- 29197083
TI  - Changes in ultrasonography indicators of abnormally invasive placenta during
      pregnancy.
AB  - OBJECTIVE: To ascertain whether the prevalence of ultrasonography signs of
      abnormally invasive placenta (AIP) changes during pregnancy. METHODS: The present
      retrospective analysis included women with a prenatal diagnosis of AIP that was
      confirmed at delivery between January 1, 2007, and April 30, 2017, at the
      Department of Obstetrics and Gynaecology, Arnas Civico Hospital, Palermo, Italy.
      Ultrasonography signs of AIP were recorded at four different intervals during
      pregnancy: early first (6-9 weeks), first (11-14 weeks), second (15-24 weeks),
      and third trimester (25-36 weeks). RESULTS: There were 105 pregnancies included.
      Low implantation of the gestational sac was present on all ultrasonography images
      from the early first trimester compared with on 23 of 83 (27.7%) images from 11
      14 weeks of pregnancy. The identification of loss of the clear space, placental
      lacunae, bladder wall interruption, and uterovesical hypervascularity all
      increased (all P<0.001) from the early first trimester onwards; these could all
      be identified in a majority of patients at 11-14 weeks of pregnancy. CONCLUSIONS:
      The prevalence of ultrasonography signs suggestive of AIP varied throughout
      pregnancy. During the early first trimester, indicators of AIP were similar to
      those of a cesarean scar pregnancy; classical ultrasonography signs of AIP were
      already present at 11-14 weeks of pregnancy for most patients.

PMID- 29197084
TI  - Light therapy and mood in breast cancer.

PMID- 29197085
TI  - Treatment of common recalcitrant warts with topical formic acid.

PMID- 29197087
TI  - Vaginal discharge concentrations of beta-human chorionic gonadotropin,
      creatinine, and urea for the diagnosis of premature rupture of membranes.
AB  - OBJECTIVE: To determine the diagnostic value of vaginal discharge concentrations
      of beta human chorionic gonadotropin (beta-hCG), creatinine, and urea to identify
      premature rupture of membranes (PROM). METHODS: An observational cross-sectional
      study was conducted between 12 June, 2014, and 11 June, 2015, among 120 women who
      were admitted to an Iranian hospital at 28-41 weeks of pregnancy. Women with
      positive pooling and nitrazine test results were assigned to the PROM group
      (n=60), whereas those with negative test results were assigned to the control
      group (n=60). Samples of vaginal discharge were obtained. RESULTS: Mean
      concentrations of beta-hCG, urea, and creatinine were all higher in the PROM
      group than in the control group (all P=0.001). The diagnostic accuracies as
      defined by area under the curve for creatinine, urea, and beta-hCG were 0.891,
      0.895, and 0.908, respectively. The corresponding optimal cutoff values were
      20.33 MUmol/L, 0.94 mmol/L, and 39.5 IU/L, respectively. CONCLUSION: The vaginal
      discharge concentrations of all three markers exhibited favorable predictive
      value for the diagnosis of PROM; however, beta-hCG showed greater diagnostic
      accuracy than either urea or creatinine.

PMID- 29197086
TI  - Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking
      in adolescents.
AB  - BACKGROUND: Nociceptin is a key regulator linking environmental stress and
      alcohol drinking. In a genome-wide methylation analysis, we recently identified
      an association of a methylated region in the OPRL1 gene with alcohol-use
      disorders. METHODS: Here, we investigate the biological basis of this observation
      by analysing psychosocial stressors, methylation of the OPRL1 gene, brain
      response during reward anticipation and alcohol drinking in 660 fourteen-year-old
      adolescents of the IMAGEN study. We validate our findings in marchigian sardinian
      (msP) alcohol-preferring rats that are genetically selected for increased alcohol
      drinking and stress sensitivity. RESULTS: We found that low methylation levels in
      intron 1 of OPRL1 are associated with higher psychosocial stress and higher
      frequency of binge drinking, an effect mediated by OPRL1 methylation. In
      individuals with low methylation of OPRL1, frequency of binge drinking is
      associated with stronger BOLD response in the ventral striatum during reward
      anticipation. In msP rats, we found that stress results in increased alcohol
      intake and decreased methylation of OPRL1 in the nucleus accumbens. CONCLUSIONS:
      Our findings describe an epigenetic mechanism that helps to explain how
      psychosocial stress influences risky alcohol consumption and reward processing,
      thus contributing to the elucidation of biological mechanisms underlying risk for
      substance abuse.

PMID- 29197089
TI  - Nuclease-resistant 63-bp trimeric siRNAs simultaneously silence three different
      genes in tumor cells.
AB  - We designed a multimeric nuclease-resistant 63-bp trimeric small-interfering RNA
      (tsiRNA) comprising in one duplex the sequence of siRNAs targeting mRNAs of MDR1,
      LMP2, and LMP7 genes. We show that such tsiRNA is able to suppress the expression
      of all the target genes independently and with high efficiency, acting via a
      Dicer-dependent mechanism. tsiRNA is diced into 42- and 21-bp duplexes inside the
      cell. tsiRNA-induced gene silencing is characterized by kinetics similar to that
      of canonical siRNA, while the silencing efficiency is significantly higher than
      that of canonical siRNA with the same sequence.

PMID- 29197090
TI  - Syndrome of Transient Headache and Neurologic Deficits With Cerebrospinal Fluid
      Lymphocitosis Should Be Considered in Children Presenting With Acute Confusional
      State.
AB  - BACKGROUND: Transient headache and neurologic deficits with cerebrospinal fluid
      lymphocytosis (HaNDL) is benign and self-limited, with neurologic deficits
      including sensory disturbance of one body side, aphasia, nausea/vomiting,
      weakness, decreased vision, homonymous hemianopsia, photophobia. Acute
      confusional state can rarely occur. Papilledema and intracranial hypertension
      have also been described. It is a rare entity mainly affecting adults; however,
      it has been sporadically described in children and adolescents. MAIN FINDINGS: In
      this clinical observational study, we describe a clinical series of three
      consecutive pediatric patients being diagnosed with HaNDL after presenting with
      altered consciousness, papilledema, and increased intracranial pressure. They all
      recovered without relapses. CONCLUSION: Presentation during childhood and
      adolescence is rare; the majority of pediatric cases presented with altered
      consciousness, which is infrequent in HaNDL. This may suggest that in childhood
      this symptom might be more common than in adults. All three patients presented
      with increased intracranial pressure and papilledema, thus suggesting that these
      aspects should be investigated in all patients presenting with this clinical
      pattern. Finally, all our patients began to suffer from migraine. This feature,
      together with the benign course of the disease, could favor the hypothesis of a
      migrainous pathophysiology of this syndrome, although this remains a speculative.

PMID- 29197088
TI  - Inhibition of MK2 suppresses IL-1beta, IL-6, and TNF-alpha-dependent colorectal
      cancer growth.
AB  - Colorectal cancer (CRC) development and progression is associated with chronic
      inflammation. We have identified the MAPK-activated protein kinase 2 (MK2)
      pathway as a primary mediator of inflammation in CRC. MK2 signaling promotes
      production of proinflammatory cytokines IL-1beta, IL-6 and TNF-alpha. These
      cytokines have been implicated in tumor growth, invasion and metastasis. For the
      first time, we investigate whether MK2 inhibition can improve outcome in two
      mouse models of CRC. In our azoxymethane/dextran sodium sulfate (AOM/DSS) model
      of colitis-associated CRC, MK2 inhibitor treatment eliminated murine tumor
      development. Using the implanted, syngeneic murine CRC cell line CT26, we observe
      significant tumor volume reduction following MK2 inhibition. Tumor cells treated
      with MK2 inhibitors produced 80% less IL-1beta, IL-6 and TNF-alpha and
      demonstrated decreased invasion. Replenishment of downstream proinflammatory MK2
      mediated cytokines (IL-1beta, IL-6 and TNF-alpha) to tumors led to restoration of
      tumor proliferation and rapid tumor regrowth. These results demonstrate the
      importance of MK2 in driving proinflammatory cytokine production, its relevance
      to in vivo tumor proliferation and invasion. Inhibition of MK2 may represent an
      attractive therapeutic target to suppress tumor growth and progression in
      patients.

PMID- 29197091
TI  - Cost-effectiveness of cognitive therapy as an early intervention for post
      traumatic stress disorder in children and adolescents: a trial based evaluation
      and model.
AB  - BACKGROUND: Untreated post-traumatic stress disorder (PTSD) in children and
      adolescents is associated with a considerable economic burden on the health
      system, families and society. Recent research has demonstrated the potential
      efficacy of cognitive therapy as an early intervention for PTSD in children and
      adolescents. Children who experienced a single traumatic event in the previous
      two to six months and were randomized to cognitive therapy for PTSD (CT-PTSD)
      were significantly more likely to be PTSD-free compared to those randomized to
      usual care represented by waitlist control. The current study evaluated the
      economic impact of improvements in the treatment of PTSD in children and
      adolescents. METHODS: A cost-effectiveness analysis was conducted from the
      national health service/personal social services perspective with outcomes
      expressed as quality-adjusted life years (QALYs). Patient level costs and
      outcomes were collected during the 11 week clinical trial and extrapolated to a
      three year time horizon using economic modelling methods. Uncertainty was
      estimated using probabilistic sensitivity analysis and assumptions were tested
      using one way sensitivity analysis. RESULTS: The incremental cost-effectiveness
      ratio at 3 years was L2,205 per QALY with a 60%-69% probability of CT-PTSD being
      cost-effective compared to usual care at the UK L20,000 to L30,000 per QALY
      decision threshold. CONCLUSIONS: This study provides preliminary evidence for the
      cost-effectiveness of cognitive therapy in this treatment population. Larger
      pragmatic trials with longer follow-up are indicated.

PMID- 29197093
TI  - The association between irisin and muscle metabolism in different thyroid
      disorders.
AB  - BACKGROUND: Irisin is a new adipo-myokine, encoded by the FNDC5 gene. Currently,
      there is a discussion regarding the relation between thyroid function and irisin
      concentration. This prospective study assesses the influence of thyrometabolic
      changes on serum irisin concentration in association with altered muscle
      metabolism. This is performed on a large cohort of patients affected by severe
      hypo- or hyperthyroidism, as well as by the expression of the FNDC5 gene in
      thyroid tissue affected by different pathologies. METHODS: The study group
      comprised 119 patients with newly diagnosed severe hyperthyroidism or
      hypothyroidism, and a control group of 45 healthy subjects. Body composition,
      serum irisin concentrations, and thyroid-related hormones, creatine kinase,
      dystrophin and titin concentrations were evaluated. FNDC5 expression was also
      analysed in tissue samples from 80 patients with nontoxic multinodular goitre,
      toxic goitre, Graves' disease and papillary thyroid cancer. RESULTS: Irisin
      concentration was lower in patients with prolonged hypothyroidism. There was a
      tendency towards lower dystrophin and titin concentrations in patients with
      hypothyroidism and hyperthyroidism. Restoration of euthyroidism in patients with
      hypothyroidism resulted in a decreased muscle mass with an increase in irisin
      concentrations, while the hyperthyroid group showed an increase in fat mass.
      Statistically significant overexpression of FNDC5 gene was found in patients with
      toxic goitre as compared to Graves' disease, papillary thyroid cancer and
      controls. CONCLUSIONS: The presented data support the theory that irisin
      concentration changes are associated with prolonged hypothyroidism and might
      primarily constitute the result of prolonged myopathy. These changes are most
      likely not related to the expression of the FNDC5 gene in the thyroid gland.

PMID- 29197092
TI  - Concomitant Psychiatric and Nonalcohol-Related Substance Use Disorders Among
      Hospitalized Patients with Alcoholic Liver Disease in the United States.
AB  - BACKGROUND: Despite that the epidemiological studies on the comorbidity of
      alcohol misuse and psychiatric disorders have been studied, less is known about
      the magnitude of these disorders among patients with alcoholic liver disease
      (ALD). Our aim was to determine the prevalence of psychiatric and substance use
      disorders among hospitalized ALD patients in the United States. METHODS: We
      utilized a single-level clinical classification software to identify patients
      with ALD and psychiatric/substance use disorders from the 2011 National Inpatient
      Sample data. The primary outcome was the prevalence of these disorders among
      hospitalized patients with ALD (n = 74,972) compared to those with chronic liver
      diseases not caused by alcohol (n = 350,140) and those without underlying liver
      diseases (n = 1,447,063). RESULTS: The prevalence of adjustment disorder, anxiety
      disorder, posttraumatic stress disorder, and depression was significantly higher
      among hospitalized patients with ALD when compared to those with chronic liver
      diseases not caused by alcohol (all with p-values <0.05). Younger age, female
      gender, and White race were the independent predictors of psychiatric/substance
      use disorders among hospitalized patients with ALD. CONCLUSIONS: Hospitalized
      patients with ALD have significantly high prevalence of concomitant psychiatric
      and substance abuse disorders when compared to those with chronic liver diseases
      not caused by alcohol and those without underlying liver diseases. Screening and
      appropriate intervention should be implemented as part of routine clinical care
      for these patients.

PMID- 29197094
TI  - Plasma NT-proBNP and Cell-Free DNA Concentrations after Prolonged Strenuous
      Exercise in Working Farm Dogs.
AB  - BACKGROUND: Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP)
      concentration is increased in dogs with myocardial dysfunction, and cell-free DNA
      (cfDNA) increases in numerous disease states. In humans, both of these biomarkers
      can be altered after endurance exercise. OBJECTIVE: To investigate the effect of
      prolonged strenuous exercise on circulating NT-proBNP and cfDNA concentrations in
      working farm dogs. ANIMALS: Six healthy, privately owned working farm dogs (4
      Huntaways and 2 heading dogs) from the same hill country farm in New Zealand.
      METHODS: Prospective, nonrandomised cohort study. Venous blood samples were
      collected before and after the dogs worked over 4 days. Plasma NT-proBNP
      concentrations were measured by a commercially available ELISA assay and cfDNA
      concentrations were determined by fluorometry without prior DNA extraction.
      RESULTS: The baseline (before work, Day 1) median plasma NT-proBNP concentration
      was 664 pmol/L. A linear mixed-effects model showed that work increased plasma NT
      proBNP concentrations by 101 +/- 9% (P < 0.001), but with each consecutive day of
      work, NT-proBNP concentrations declined by 16 +/- 4% (P < 0.001). The baseline
      median plasma cfDNA concentration was 653 ng/mL, and plasma cfDNA concentrations
      increased by 138 +/- 45 ng/mL after work (P = 0.004). CONCLUSIONS AND CLINICAL
      IMPORTANCE: The plasma concentration of NT-proBNP in healthy Huntaways and
      heading dogs after work can exceed the upper limit of the reference range.
      Results in dogs sampled on the day of prolonged strenuous exercise should be
      interpreted with caution. Plasma concentrations of cfDNA also increase with
      exercise, but further studies are needed to establish reference ranges in healthy
      dogs.

PMID- 29197095
TI  - Oro-facial pain and temporomandibular disorders classification systems: A
      critical appraisal and future directions.
AB  - It is a difficult undertaking to design a classification system for any disease
      entity, let alone for oro-facial pain (OFP) and more specifically for
      temporomandibular disorders (TMD). A further complication of this task is that
      both physical and psychosocial variables must be included. To augment this
      process, a two-step systematic review, adhering to PRISMA guidelines, of the
      classification systems published during the last 20 years for OFP and TMD was
      performed. The first search step identified 190 potential citations which
      ultimately resulted in only 17 articles being included for in-depth analysis and
      review. The second step resulted in only 5 articles being selected for inclusion
      in this review. Five additional articles and four classification
      guidelines/criteria were also included due to expansion of the search criteria.
      Thus, in total, 14 documents comprising articles and guidelines/criteria (8
      proposals of classification systems for OFP; 6 for TMD) were selected for
      inclusion in the systematic review. For each, a discussion as to their
      advantages, strengths and limitations was provided. Suggestions regarding the
      future direction for improving the classification process with the use of
      ontological principles rather than taxonomy are discussed. Furthermore, the
      potential for expanding the scope of axes included in existing classification
      systems, to include genetic, epigenetic and neurobiological variables, is
      explored. It is therefore recommended that future classification system proposals
      be based on combined approaches aiming to provide archetypal treatment-oriented
      classifications.

PMID- 29197097
TI  - Family Interventions for Populations Exposed to Traumatic Stress Related to War
      and Violence.

PMID- 29197096
TI  - Observations on the origin of ovarian cortical inclusion cysts in women
      undergoing risk-reducing salpingo-oophorectomy.
AB  - AIMS: Evidence suggests that up to 70% of high-grade serous ovarian carcinomas
      (HGSCs) arise potentially from fallopian tube fimbriae, and that many of the
      remaining cases arise from within the ovary in cortical inclusion cysts (CICs)
      with a Mullerian phenotype (Mullerian-CICs). It has been proposed that Mullerian
      CICs arise either from metaplasia of mesothelial ovarian surface epithelium (OSE)
      entrapped within the ovary after ovulation or from normal tubal cells entrapped
      postovulation. However, this proposal is controversial. We therefore conducted a
      study of CICs in women, most of them BRCA1/2 mutation carriers, undergoing risk
      reducing salpingo-oophorectomy at our institution from 2000 to 2014. METHODS AND
      RESULTS: We used immunohistochemistry for PAX8, a Mullerian marker, and
      calretinin, a mesothelial marker to classify CIC cells. In 499 CICs from 59
      women, 72.3% were positive for PAX8 (PAX8+ ): >=10% of CIC cells positive; 43.5%
      positive for calretinin (calretinin+ ). The proportion of PAX8+ CICs increased
      from 62.9% in premenopausal to 80.5% in postmenopausal patients. The proportion
      of calretinin+ CICs decreased from 52.6% to 35.6%, respectively. There was
      significant overlap of PAX8 and calretinin positivity: 82 (16.4%) CICs were PAX8+
      /calretinin+ ; 43 (40.2%) of these 82 demonstrated PAX8+ /calretinin+ in the same
      cells. CONCLUSIONS: These results, and the increased ratio of PAX8+ to
      calretinin+ CICs from premenopausal to postmenopausal, show that many PAX8+ CICs
      probably arise from metaplasia of OSE-derived CICs. The proportion of PAX+
      /calretinin- CICs arising from OSE-derived CICs is unclear, but our results
      strongly support the proposal that many Mullerian-CICs arise from OSE via
      metaplasia.

PMID- 29197098
TI  - A longitudinal investigation of the role of parental responses in predicting
      children's post-traumatic distress.
AB  - BACKGROUND: While parental post-trauma support is considered theoretically
      important for child adjustment, empirical evidence concerning the specific
      aspects of parental responding that influence child post-traumatic distress, or
      the processes via which any such impacts occur, is extremely limited. We
      conducted a longitudinal examination of whether parental post-trauma appraisals,
      trauma-specific support style and general parenting style predicted child post
      traumatic stress symptom severity (PTSS) following trauma; and whether such
      influences operated via the child's own appraisals and coping style. METHOD: We
      recruited 132 parent-child pairs following children's experience of acute trauma.
      We examined whether parental responses assessed at 1-month post-trauma, predicted
      child PTSS at 6-month follow-up. Parental trauma-specific appraisals and
      responses, and general parenting style, were assessed via both self-report and
      direct observations. Child-report questionnaires were used to assess PTSS and
      potential mediators. RESULTS: Initial parent negative appraisals and
      encouragement of avoidant coping were associated with higher child-reported PTSS
      at 6-month follow-up. Predictive effects were maintained even when controlling
      for initial child symptom levels. Observational assessments broadly supported
      conclusions from self-report. There was evidence that parental influences may
      operate, in part, by influencing the child's own appraisals and coping responses.
      In contrast, there was no evidence for an influence of more "adaptive" support or
      general parenting style on child PTSS. CONCLUSIONS: Findings provide important
      insight into how elements of social support may influence child post-trauma
      outcomes.

PMID- 29197099
TI  - Identification of patterns of factors preceding severe or life-threatening asthma
      exacerbations in a nationwide study.
AB  - BACKGROUND: Reducing near-fatal asthma exacerbations is a critical problem in
      asthma management. OBJECTIVES: To determine patterns of factors preceding asthma
      exacerbations in a real-world setting. METHODS: In a nationwide prospective study
      of 190 patients who had experienced near-fatal asthma exacerbation, cluster
      analysis was performed using asthma symptoms over the 2-week period before
      admission. RESULTS: Three distinct clusters of symptoms were defined employing
      the self-reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening
      within 7.4 hours from moderate attack to admission, young to middle-aged patients
      with low Body mass index and tendency to depression who had stopped anti-asthma
      medications, smoked, and hypersensitive to environmental triggers and furred
      pets. Cluster B (40.0%): fairly rapid worsening within 48 hours, mostly middle
      aged and older, relatively good inhaled corticosteroid (ICS) or ICS/long-acting
      beta-agonist (LABA) compliance, and low perception of dyspnea. Cluster C (17.9%):
      slow worsening over 10 days before admission, high perception of dyspnea,
      smokers, and chronic daily mild-moderate symptoms. There were no differences in
      overuse of short-acting beta-agonists, baseline asthma severity, or outcomes
      after admission for patients in these 3 clusters. CONCLUSION: To reduce severe or
      life-threatening asthma exacerbation, personalized asthma management plans should
      be considered for each cluster. Improvement of ICS and ICS/LABA compliance and
      cessation of smoking are important in cluster A. To compensate for low perception
      of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric
      oxide would be useful for patients in cluster B. Avoidance of environmental
      triggers, increase usual therapy, or new anti-type 2 response-targeted therapies
      should be considered for cluster C.

PMID- 29197101
TI  - A biocompatible decellularized pulp scaffold for regenerative endodontics.
AB  - AIM: To investigate the feasibility of decellularizing the entire dental pulp
      using a mild treatment protocol to develop a decellularized biological
      extracellular matrix scaffold for use in regenerative endodontic procedures.
      METHODOLOGY: Decellularized human dental pulps were assessed using histological
      and immunohistochemical methods, scanning electron microscope and DNA
      quantification assay. Cytotoxicity assays to determine decellularized scaffold
      biocompatibility were also performed. Decellularized scaffolds were seeded with
      human dental pulp stem cells and cell viability assessed using Live/Dead(r)
      stain. Quantitative data were analysed statistically using Student's t-test and
      one-way analysis of variance to compare mean values between groups depending on
      group numbers. RESULTS: Assessment of decellularized tissues revealed an
      acellular matrix with preservation of native tissue histoarchitecture and
      composition. Decellularized tissues showed no evidence of cytotoxicity, with cell
      growth in direct contact with the scaffold and no reduction in cellular activity
      following extract incubation. Furthermore, the scaffold was able to support human
      dental pulp stem cell viability and attachment following recellularization.
      CONCLUSIONS: Promising results were observed in developing a decellularized
      biological scaffold derived from the dental pulp with the perseveration of
      extracellular structural components which are required for tissue-specific
      regeneration.

PMID- 29197100
TI  - The high societal costs of childhood conduct problems: evidence from
      administrative records up to age 38 in a longitudinal birth cohort.
AB  - BACKGROUND: Children with conduct problems that persist into adulthood are at
      increased risk for future behavioral, health, and social problems. However, the
      longer term public service usage among these children has not been fully
      documented. To aid public health and intervention planning, adult service usage
      across criminal justice, health care, and social welfare domains is compared
      among all individuals from a representative cohort who followed different conduct
      problem trajectories from childhood into adulthood. METHODS: Participants are
      from the Dunedin Multidisciplinary Health and Development Study, a prospective,
      representative cohort of consecutive births (N = 1,037) from April 1972 to March
      1973 in Dunedin, New Zealand. Regression analyses were used to compare levels of
      public service usage up to age 38, gathered via administrative and electronic
      medical records, between participants who displayed distinct subtypes of
      childhood conduct problems (low, childhood-limited, adolescent-onset, and life
      course persistent). RESULTS: Children exhibiting life-course persistent conduct
      problems used significantly more services as adults than those with low levels of
      childhood conduct problems. Although this group comprised only 9.0% of the
      population, they accounted for 53.3% of all convictions, 15.7% of emergency
      department visits, 20.5% of prescription fills, 13.1% of injury claims, and 24.7%
      of welfare benefit months. Half of this group (50.0%) also accrued high service
      use across all three domains of criminal justice, health, and social welfare
      services, as compared to only 11.3% of those with low conduct problems (OR =
      7.27, 95% CI = 4.42-12.0). CONCLUSIONS: Conduct problems in childhood signal high
      future costs in terms of service utilization across multiple sectors. Future
      evaluations of interventions aimed at conduct problems should also track
      potential reductions in health burden and service usage that stretch into
      midlife.

PMID- 29197102
TI  - Evaluation of a computerized cognitive behavioural therapy programme, MindWise
      (2.0), for adults with mild-to-moderate depression and anxiety.
AB  - OBJECTIVES: To investigate the acceptability and utility of a newly developed
      computerized cognitive behavioural therapy (cCBT) programme, MindWise (2.0), for
      adults attending Irish primary care psychology services. METHOD: Adult primary
      care psychology service users across four rural locations in Ireland were invited
      to participate in this study. A total of 60 service users participated in the
      MindWise (2.0) treatment group and compared to 22 people in a comparison waiting
      list control group. Participants completed pre- and post-intervention outcome
      measures of anxiety, depression, and work/social functioning. RESULTS: At post
      intervention, 25 of 60 people in the MindWise (2.0) condition had fully completed
      the programme and 19 of 22 people in the waiting list condition provided time 2
      data. Relative to those in the control group, the MindWise (2.0) participants
      reported significantly reduced symptoms of anxiety and no change in depression or
      work/social functioning. CONCLUSIONS: The newly developed cCBT programme,
      MindWise (2.0), resulted in significant improvements on a measure of anxiety and
      may address some barriers to accessing more traditional face-to-face mental
      health services for adults in a primary care setting. Further programme
      development and related research appears both warranted and needed to lower
      programme drop-out, establish if gains in anxiety management are maintained over
      time, and support people in a primary care context with depression. PRACTITIONER
      POINTS: There is a growing evidence base that computerized self-help programmes
      can assist in a stepped-care approach to adult mental health service provision.
      These programmes require further development to address issues such as high
      dropout, the development of equally effective transdiagnostic content, and
      greater effectiveness in the country of origin. This study evaluated the
      acceptability and utility of a brief online CBT programme for adults referred due
      to anxiety or low mood to primary care psychology services in the national health
      service in Ireland. Results indicate that 42% of people completed the programme
      and experienced a significant reduction in anxiety but not depression and no
      improvement in work or social adjustment compared to similar adults on a waiting
      list for services. This study suggests the programme warrants further development
      and research and may in time become a useful and suitable intervention within the
      national health service in Ireland.

PMID- 29197103
TI  - Long-term variability of sleep bruxism and psychological stress in patients with
      jaw-muscle pain: Report of two longitudinal clinical cases.
AB  - Sleep bruxism (SB) and psychological stress are commonly considered as
      contributing factors in the aetiology of temporomandibular disorder (TMD) pain.
      However, the lack of longitudinal studies and fluctuating nature of SB,
      psychological stress and TMD pain have led to contradictory results regarding the
      association between the possible aetiological factors and TMD pain. In the
      present study we investigated the contribution of SB and psychological stress to
      TMD pain in a longitudinal study of 2 clinical TMD pain cases during a 6-week
      study protocol. Two female volunteers with clinically diagnosed myalgia based on
      the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) participated in
      the study. Questionnaires were used to record jaw-muscle pain and psychological
      stress experience, and an ambulatory polysomnography technique was used to record
      SB intensity. Visual analysis of the data revealed that the intensity of TMD pain
      was not hardwired, neither with psychological stress experience nor with
      increased SB activity. Within the limitations of single-patient clinical cases
      design, our study suggested that the presence of TMD pain cannot be explained by
      a simple linear model which takes psychological stress or SB into account. It
      also seems that psychological stress was a more important predictor factor for
      TMD pain than SB.

PMID- 29197104
TI  - The effect of dronabinol in a male patient with anorexia nervosa suffering from
      severe acute urge to be physically active.
AB  - OBJECTIVE: A 27-year-old male suffering from chronic anorexia nervosa was
      admitted for inpatient psychotherapy suffering from severe urge to be physically
      active. METHODS: An off-label treatment with dronabinol was initiated, to reduce
      his symptoms related to that urge. Several attempts to reduce symptoms including
      intensive psychotherapy and several psychopharmacological agents had failed in
      the past. RESULTS: Following treatment with 7.5 mg dronabinol twice a day, the
      patient reported a significant reduction in his acute urge to be physically
      active. Also eating disorder-specific cognitions and compulsive behaviors
      remitted. DISCUSSION: Previous studies have applied much lower doses and showed
      no effect of dronabinol upon the urge to be physically active. Up to date, the
      patient reported no side effects, especially no psychotropic effects.
      Implications of this case report are discussed.

PMID- 29197105
TI  - Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and
      chronic rhinosinusitis: The one airway concept revisited.
AB  - Allergic rhinitis (AR), chronic rhinosinusitis (CRS) and asthma often co-exist.
      The one airway model proposes that disease mechanisms occurring in the upper
      airway may mirror lower airway events. Airway remodelling is the term used to
      describe tissue structural changes that occur in a disease setting and reflect
      the dynamic process of tissue restructuring during wound repair. Remodelling has
      been long identified in the lower airways in asthma and is characterized by
      epithelial shedding, goblet cell hyperplasia, basement membrane thickening,
      subepithelial fibrosis, airway smooth muscle hyperplasia and increased
      angiogenesis. The concept of upper airway remodelling has only recently been
      introduced, and data so far are limited and often conflicting, an indication that
      more detailed studies are needed. Whilst remodelling changes in AR are limited,
      CRS phenotypes demonstrate epithelial hyperplasia, increased matrix deposition
      and degradation along with accumulation of plasma proteins. Despite extensive
      research over the past years, the precise cellular and molecular mechanisms
      involved in airway remodelling remain incompletely defined. This review describes
      our current rather limited understanding of airway remodelling processes in AR,
      CRS and asthma and presents mechanisms both shared and distinct between the upper
      and lower airways. Delineation of shared and disease-specific pathogenic
      mechanisms of remodelling between the sinonasal system and the lung may guide the
      rational design of more effective therapeutic strategies targeting upper and
      lower airways concomitantly and improving the health of individuals with
      inflammatory airway diseases.

PMID- 29197106
TI  - Practitioner Review: School refusal: developments in conceptualisation and
      treatment since 2000.
AB  - BACKGROUND: A generation has passed since the literature on the
      conceptualisation, assessment and treatment of school refusal was reviewed in
      this journal (Elliott, ). In the light of considerable gaps in the literature,
      identified at that time, and growing international interest, the current paper
      sought to identify progress subsequently made this century. METHODS: We open with
      discussion of continuing conceptual uncertainty as to whether school refusal
      should incorporate both truancy and absenteeism marked by anxiety and distress.
      We then consider progress in treatment, and conclude by examining prognosis and
      subsequent adult functioning. In selecting intervention studies for review, our
      primary focus has been upon RCTS, systematic reviews and meta-analyses. RESULTS:
      The literature review indicates that, since the turn of the century, there has
      been little substantial advance in knowledge that can guide practitioners. Many
      of the issues raised in the 1999 paper, in particular, conceptual confusion over
      this heterogeneous condition, a dearth of rigorous RCT designs, limited knowledge
      of underlying mechanisms and uncertainty as to the long-term effects of specific
      forms of intervention, are little clearer than before. CONCLUSIONS: While several
      sound publications are available to guide intervention for school refusal, there
      is a continuing need for rigorous studies that can provide evidence to support
      individualised and tailored responses to an incapacitating problem with many
      causes and manifestations. While a multisystemic response to intervention
      approach is considered attractive, the practicalities of operating this across
      disparate professional borders are likely to present a long-term challenge.

PMID- 29197107
TI  - Developmental stability of general and specific factors of psychopathology from
      early childhood to adolescence: dynamic mutualism or p-differentiation?
AB  - BACKGROUND: Recent research indicates that the best-fitting structural model of
      psychopathology includes a general factor capturing comorbidity (p) and several
      more specific, orthogonal factors. Little is known about the stability of these
      factors, although two opposing developmental processes have been proposed:
      dynamic mutualism suggests that symptom-level interaction and reinforcement may
      lead to a strengthening of comorbidity (p) over time, whereas p-differentiation
      suggests a general vulnerability to psychopathology that gives way to
      increasingly distinct patterns of symptoms over time. In order to test both
      processes, we examine two forms of developmental stability from ages 2 to 14
      years: strength (i.e., consistency in the amount of variance explained by general
      and specific factors) and phenotypic stability (i.e., homotypic and heterotypic
      continuity). METHODS: Data are from the NICHD Study of Early Child Care and Youth
      Development. Psychopathology symptoms were assessed nine times between ages 2 and
      14 years (n = 1,253) using the Child Behavior Checklist completed by mothers.
      Confirmatory bifactor modeling was used to test structural models of
      psychopathology at each age. Consistency in strength was examined by calculating
      the Explained Common Variance (ECV) and phenotypic stability was investigated
      with cross-lagged modeling of the general and specific factors. RESULTS: Bifactor
      models fit the data well across this developmental period. ECV values were
      reasonably consistent across development, with the general factor accounting for
      the majority of shared variance (61%-71%). Evidence of both homotypic and
      heterotypic continuity emerged, with most heterotypic continuity involving the
      general factor, as it both predicted and was predicted by specific factors.
      CONCLUSIONS: A bifactor model effectively captures psychopathological comorbidity
      from early childhood through adolescence. The longitudinal associations between
      the general and specific factors provide evidence for both the hypothesized
      processes (dynamic mutualism and p-differentiation) occurring through
      development.

PMID- 29197108
TI  - Refining a Claims-based Algorithm to Estimate Biologic Medication Effectiveness
      and Cost per Effectively Treated Patient with Rheumatoid Arthritis.
AB  - BACKGROUND: Claims data generally lack information on clinical outcomes. However,
      a validated claims-based algorithm for estimating the effectiveness of biologic
      agents in treating rheumatoid arthritis (RA) was recently developed and applied
      to various databases. OBJECTIVES: The objectives of the study were to implement a
      claims-based algorithm in a large nationwide database to estimate medication
      effectiveness and cost for patients with RA using biologic disease-modifying
      antirheumatic drugs (DMARDs) and to assess the effect of eliminating one
      criterion from the algorithm on results. METHODS: The DMARD groups included
      patients initiated on etanercept, adalimumab, abatacept, or infliximab. Patients
      were categorized as effectively treated if they met these six criteria: a
      medication possession ratio of 80% or greater; no escalation in biologic dose; no
      switch in biologics; no new nonbiologic DMARD; no new or increased oral
      glucocorticoid treatment; and no more than one glucocorticoid injection. In a
      follow-up analysis, the dose-escalation criterion was removed because an increase
      in dose for infliximab may be appropriate. Average costs for RA-related
      medications were calculated for each DMARD patient group and divided by the
      number of patients who met all six effectiveness criteria. RESULTS: A total of
      1196 individuals were included in the analysis. Using the algorithm, the index
      biologic was categorized as effective for 25.4% of patients overall: 30.3%
      (102/337) of etanercept, 27.6% (104/377) of adalimumab, 32.7% (37/113) of
      abatacept, and 16.5% (61/369) of infliximab patients. Total costs for RA
      medication costs per effectively treated patient ranged from more than $80,000
      for infliximab to ~$43,000-$46,000 for the other three groups. Removing the no
      dose-escalation criterion drastically reduced the cost per effectively treated
      patient in the infliximab group (to ~$42,000). CONCLUSIONS: Using the original
      six-criteria claims-based algorithm in a large claims database, infliximab was
      the least-effective biologic agent and had the highest medication cost per
      effectively treated patient. However, when a follow-up analysis removed the dose
      escalation exclusion criterion, the four groups had similar effectiveness and
      medication costs per effectively treated patient with RA.

PMID- 29197109
TI  - Prospective test of the developmental propensity model of antisocial behavior:
      from childhood and adolescence into early adulthood.
AB  - BACKGROUND: The developmental propensity model of antisocial behavior posits that
      several dispositional characteristics of children transact with the environment
      to influence the likelihood of learning antisocial behavior across development.
      Specifically, greater dispositional negative emotionality, greater daring, and
      lower prosociality-operationally, the inverse of callousness- and lower cognitive
      abilities are each predicted to increase risk for developing antisocial behavior.
      METHODS: Prospective tests of key predictions derived from the model were
      conducted in a high-risk sample of 499 twins who were assessed on dispositions at
      10-17 years of age and assessed for antisocial personality disorder (APD)
      symptoms at 22-31 years of age. Predictions were tested separately for parent and
      youth informants on the dispositions using multiple regressions that adjusted for
      oversampling, nonresponse, and clustering within twin pairs, controlling
      demographic factors and time since the first assessment. RESULTS: Consistent with
      predictions, greater numbers of APD symptoms in adulthood were independently
      predicted over a 10-15 year span by higher youth ratings on negative emotionality
      and daring and lower youth ratings on prosociality, and by parent ratings of
      greater negative emotionality and lower prosociality. A measure of working memory
      did not predict APD symptoms. CONCLUSIONS: These findings support future research
      on the role of these dispositions in the development of antisocial behavior.

PMID- 29197110
TI  - Macrophage activation syndrome and post-transplant microangiopathy following
      haploidentical bone marrow transplantation for sickle cell anemia.

PMID- 29197111
TI  - Evaluation of swallowing ability using swallowing sounds in maxillectomy
      patients.
AB  - Maxillectomy for oral tumours often results in debilitating oral hypofunction,
      which markedly decreases quality of life. Dysphagia, in particular, is one of the
      most serious problems following maxillectomy. This study used swallowing sounds
      as a simple evaluation method to evaluate swallowing ability in maxillectomy
      patients with and without their obturator prosthesis placed. Twenty-seven
      maxillectomy patients (15 men, 12 women; mean age 66.0 +/- 12.1 years) and 30
      healthy controls (14 men, 16 women; mean age 44.9 +/- 21.3 years) were recruited
      for this study. Participants were asked to swallow 4 mL of water, and swallowing
      sounds were recorded using a throat microphone. Duration of the acoustic signal
      and duration of peak intensity (DPI) were measured. Duration of peak intensity
      was significantly longer in maxillectomy patients without their obturator than
      with it (P < .05) and was significantly longer in maxillectomy patients without
      their obturator than in healthy controls (P < .025 after Bonferroni correction).
      With the obturator placed, DPI was significantly longer in maxillectomy patients
      who had undergone soft palate resection than in those who had not (P < .05).
      These results suggest swallowing ability in maxillectomy patients could be
      improved by wearing an obturator prosthesis, particularly during the oral stage.
      However, it is difficult to improve the oral stage of swallowing in patients who
      have undergone soft palate resection even with obturator placement.

PMID- 29197112
TI  - Invasion in breast lesions: the role of the epithelial-stroma barrier.
AB  - Despite the significant biological, behavioural and management differences
      between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast,
      they share many morphological and molecular similarities. Differentiation of
      these two different lesions in breast pathological diagnosis is based typically
      on the presence of an intact barrier between the malignant epithelial cells and
      stroma; namely, the myoepithelial cell (MEC) layer and surrounding basement
      membrane (BM). Despite being robust diagnostic criteria, the identification of
      MECs and BM to differentiate in-situ from invasive carcinoma is not always
      straightforward. The MEC layer around DCIS may be interrupted and/or show an
      altered immunoprofile. MECs may be absent in some benign locally infiltrative
      lesions such as microglandular adenosis and infiltrating epitheliosis, and
      occasionally in non-infiltrative conditions such as apocrine lesions, and in
      these contexts this does not denote malignancy or invasive disease with
      metastatic potential. MECs may also be absent around some malignant lesions such
      as some forms of papillary carcinoma, yet these behave in an indolent fashion
      akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend
      anteriorly from the ducts to infiltrate the epidermis of the nipple but do not
      typically infiltrate through the BM into the dermis. Conversely, BM-like material
      can be seen around invasive carcinoma cells and around metastatic tumour cell
      deposits. Here, we review the role of MECs and BM in breast pathology and
      highlight potential clinical implications. We advise caution in interpretation of
      MEC features in breast pathology and mindfulness of the substantive evidence base
      in the literature associated with behaviour and clinical outcome of lesions
      classified as benign on conventional morphological examination before changing
      classification to an invasive lesion on the sole basis of MEC characteristics.

PMID- 29197114
TI  - The correlation between SNPs within the gene of adrenergic receptor and
      neuropeptide Y and risk of cervical vertigo.
AB  - BACKGROUND: The current investigation was aimed to explore the potential
      associations of SNPs within ADRB2, ADRB1, NPY, and ADRA1A with risk and prognosis
      of cervical vertigo. METHODS: Altogether 216 patients with cervical vertigo and
      204 healthy controls were gathered, and their DNAs were extracted utilizing the
      whole-blood DNA extraction kit. Besides, the PCR reactions were conducted using
      the TaqManR single nucleotide polymorphism (SNP) genotyping assays, and the SNPs
      were detected on the 7900HT real-time fluorogenic quantitative polymerase chain
      reaction (PCR) instrument. Finally, the severity of cervical vertigo was
      classified according to the JOA scoring, and the recovery rate (RR) of cervical
      vertigo was calculated in light of the formula as: [Formula: see text] RESULTS:
      The SNPs within ADRA1A [rs1048101 (T>C) and rs3802241 (C>T)], NPY [rs16476 (A>C),
      rs16148 (T>C), and rs5574 (C>T)], ADRB1 [rs28365031 (A>G)] and ADRB2 [rs2053044
      (A>G)] were all significantly associated with regulated risk of cervical vertigo
      (all P < .05). Haplotypes of ADRA1A [CT and TC] and NPY [CCT and ATT] were also
      suggested as the susceptible factors of cervical vertigo in comparison with other
      haplotypes. Furthermore, the SNPs within ADRA1A [rs1048101 (T>C)], NPY [rs16476
      (A>C), rs16148 (T>C)], as well as ADRB1 [rs28365031 (A>G)] all appeared to
      predict the prognosis of cervical vertigo in a relatively accurate way (all P <
      .05). Ultimately, the haplotypes of ADRA1A (CC) and NPY (CCT) tended to decrease
      the RR. CONCLUSIONS: The SNPs within ADRB2, ADRB1, NPY, and ADRA1A might act as
      the diagnostic biomarkers and treatment targets for cervical vertigo.

PMID- 29197113
TI  - Pyelonephritis in Dogs: Retrospective Study of 47 Histologically Diagnosed Cases
      (2005-2015).
AB  - BACKGROUND: The clinicopathologic aspects of pyelonephritis have not been
      reported in companion animals. HYPOTHESIS/OBJECTIVES: To evaluate the prevalence
      of pyelonephritis diagnosed in dogs in a academic referral population, describe
      the clinical signs and the diagnostic test results in dogs with pyelonephritis,
      and identify concurrent disorders in order to determine potential risk factors
      for pyelonephritis. ANIMALS: Forty-seven dogs with a histopathologic diagnosis of
      pyelonephritis from the teaching hospitals of three Canadian veterinary colleges.
      METHODS: Retrospective case series. Review of medical records and renal
      histologic sections. RESULTS: Pyelonephritis was diagnosed in 0.4-1.3% of the
      cases at necropsy. Clinical signs included anorexia or inappetence (n = 27, 57%),
      lethargy (n = 24, 51%), vomiting (n = 17, 36%), and dehydration (n = 12, 25%).
      Thirty-five dogs (75%) had concomitant disease(s). Escherichia coli was the most
      common pathogen isolated (37%). Pyelonephritis was classified as acute (n = 12,
      26%), subacute (n = 9, 19%), and chronic (n = 26, 55%) disease; and mild (n = 7,
      15%), moderate (n = 11, 24%), and severe (n = 28, 61%). Fever was significantly
      associated with histopathologically subacute pyelonephritis (P = 0.01).
      CONCLUSIONS: In referral hospitals, pyelonephritis has a very low prevalence at
      necropsy. Nonspecific clinical presentation, concomitant diseases, and high
      variability in the diagnostic tests results make the antemortem diagnosis of
      pyelonephritis challenging. Neither the histopathologic stage nor the severity of
      the pyelonephritis was associated with fever, lumbar pain, or signs of a urinary
      tract infection (ie, lower urinary tract infection, upper urinary tract
      infection, or both) except for subacute pyelonephritis which was associated with
      fever.

PMID- 29197116
TI  - Biological Systems Are a Common Link Between Alcohol Use Disorder and Co
      Occurring Psychiatric and Medical Conditions.

PMID- 29197115
TI  - Effect of Hazardous Alcohol Use During Pregnancy on Growth Outcomes at Birth:
      Findings from a South African Cohort Study.
AB  - BACKGROUND: Cohort studies have noted associations between hazardous alcohol use
      during pregnancy and infant growth outcomes, but many have not controlled for
      potential psychosocial confounders. To assess the unique contribution of
      hazardous alcohol use, we examined its effect on infant growth outcomes while
      controlling for maternal psychosocial stressors and hazardous tobacco and drug
      use in a cohort of 986 pregnant South African women enrolled into the Drakenstein
      Child Health Study between 2012 and 2015. METHODS: Data on psychosocial stressors
      and maternal risk behaviors were collected between 28 and 32 weeks of gestation.
      Participants were categorized as hazardous alcohol users if they obtained
      moderate or high scores (>10) on the Alcohol, Smoking and Substance Involvement
      Screening Test at this assessment or retrospectively reported drinking at least 2
      drinks weekly during any trimester of pregnancy. Infant growth outcomes were
      recorded at delivery. Multivariable regression models examined correlates of
      hazardous alcohol use and associations between hazardous alcohol use and birth
      outcomes. RESULTS: Overall, 13% of mothers reported hazardous alcohol use. Recent
      exposure to intimate partner violence (adjusted odds ratio (aOR) = 2.08; 95%
      confidence interval (CI): 1.37, 3.18) and hazardous tobacco use (aOR = 5.03; 95%
      CI: 2.97, 8.52) were significant correlates of hazardous alcohol use. After
      controlling for potential psychosocial confounders, hazardous alcohol use
      remained associated with lower infant weight-for-age (B = -0.35, 95% CI: -0.56, 
      0.14), height-for-age (B = -0.46, 95% CI: -0.76, -0.17), and head-circumference
      for-age z-scores (B = -0.43, 95% CI: -0.69, -0.17). CONCLUSIONS: Interventions to
      reduce hazardous alcohol use among pregnant women in South Africa are needed to
      prevent alcohol-related infant growth restrictions. As these growth deficits may
      lead to neurodevelopmental consequences, it is critical to identify alcohol
      related growth restrictions at birth and link exposed infants to early
      interventions for neurodevelopment.

PMID- 29197117
TI  - Addition of Allopurinol for Altering Thiopurine Metabolism to Optimize Therapy in
      Patients with Inflammatory Bowel Disease.
AB  - Thiopurine drugs, including azathioprine and 6-mercaptopurine, are used commonly
      in patients with inflammatory bowel disease for maintenance of remission.
      Although generally well tolerated, adverse effects lead to discontinuation in a
      significant minority of patients. Pharmacogenomic studies have suggested that
      metabolic breakdown of azathioprine in an individual is genetically determined.
      Coupled with the fact that certain thiopurine metabolites, notably 6-thioguanine
      nucleotide and 6-methylmercaptopurine, are associated with antiinflammatory
      effects and adverse effects, respectively, some investigators have examined
      intentionally shunting the metabolism of azathioprine toward increasing 6
      thioguanine nucleotide levels by using low doses of the xanthine oxidoreductase
      inhibitor allopurinol to improve efficacy and decrease toxicity of azathioprine
      in patients with inflammatory bowel disease. We performed a search of the MEDLINE
      and Embase databases for basic and clinical research reports of this modality.
      Pertinent articles were retrieved, reviewed, and assessed by the authors. Case
      series, cohort studies, and one randomized trial have investigated adding
      allopurinol to azathioprine therapy in patients with inflammatory bowel disease.
      Most reports primarily examined metabolite levels in these patients. In general,
      the literature suggests that this modality was successful at significantly
      increasing 6-thioguanine nucleotide levels while decreasing 6
      methylmercaptopurine levels. Several small reports have suggested that patients
      with increased 6-thioguanine nucleotide levels had improved symptoms or symptom
      remission. Adverse effects and discontinuation rates remained similar or were
      improved in patients who were taking a thiopurine and started allopurinol. In
      conclusion, the addition of allopurinol may be an option for optimizing
      thiopurine metabolite production in select patients with low 6-thioguanine
      nucleotide levels. Appropriate care and monitoring of these patients are
      mandatory to prevent neutropenia or other adverse effects.

PMID- 29197118
TI  - Reducing the stigma associated with anorexia nervosa: An evaluation of a social
      consensus intervention among Australian and Chinese young women.
AB  - OBJECTIVE: This study examined the effectiveness of a social consensus
      intervention in reducing stigma toward individuals with anorexia nervosa (AN)
      among women from Australia and mainland China. Moreover, the different
      predictions of informational/normative social influence theory and the social
      identity approach in terms of the effectiveness of the social consensus
      intervention were investigated. METHOD: Participants were female students from
      the Australian National University (n = 97) and Central China Normal University
      (n = 76) who reported their levels of stigma toward a fictional character with AN
      before and after receiving normative information regarding the attitudes of
      others toward people with AN. Three experimental conditions of normative
      information were utilized: in-group, out-group, and neutral. RESULTS: Chinese
      participants reported higher levels of baseline stigma across all measures than
      Australian participants. Social consensus was effective in reducing most types of
      AN stigma, and supported the social identity approach in that improvements in
      attitudinal, affective, and behavioral aspects of stigma were significantly
      greater for participants in the in-group (but not the out-group) versus the
      neutral condition. The effectiveness of the social consensus approach was not
      moderated by nationality. DISCUSSION: A social consensus approach holds potential
      as an additional strategy for reducing AN stigma, with its benefits extending
      across diverse cultural settings. Such an approach would entail ensuring that
      positive messages regarding people with AN are delivered by members of a valued
      in-group.

PMID- 29197119
TI  - Fundamental movement skills in adolescents: Secular trends from 2003 to 2010 and
      associations with physical activity and BMI.
AB  - The aim of this study was to examine the secular trends in fundamental movement
      skills (FMS) among 15- to 16-year-old adolescents at 2 assessment points
      scheduled in 2003 and 2010 and to investigate the associations between FMS,
      physical activity (PA), and body mass index (BMI). In 2003, self-reported PA,
      weight and height, and objective FMS scores were collected from 2390 students,
      and in 2010, similar data were generated from a second sample of 1346 students.
      FMS were assessed during both assessment phases using 3 identical objective FMS
      tests that were figure 8 dribbling, jumping laterally, and coordination track
      tests. This study indicated that the sum index of FMS did not change among the
      boys and the girls between 2 data collection points. However, findings
      demonstrated a secular decline in coordination test scores in both gender groups
      between 2 measurement points but an improvement in girls' object control skills
      between 2003 and 2010. The results also showed that FMS had a significant main
      effect on BMI in both gender groups, whereas the main effect of PA on BMI was not
      significant for either gender group. Results also demonstrated that there was no
      significant interaction effect between FMS and PA on BMI in either of the girls'
      or the boys' groups.

PMID- 29197121
TI  - The clinical anatomy of fibromyalgia.
AB  - Fibromyalgia is a disorder characterized by pain and a spectrum of psychological
      comorbidities, rendering treatment difficult, and often a financial burden.
      Findings regarding diagnosis, prevalence, comorbidities, and potential
      pathophysiological links are discussed herein. Fibromyalgia is a complex disorder
      and there are specific criteria that patients must meet for diagnosis, including
      scores on fibromyalgia questionnaires, commonalities of age, gender, menopause
      status, sleep disturbances, and mood symptoms. The close relationship between
      fibromyalgia and other chronic disorders should alert the physician to explore
      for comorbid illnesses. In this review of the clinical anatomy of fibromyalgia,
      we review new studies that could be significant for the current use of clinical
      interventions for patients with symptoms. Using standard search engines, the
      clinical anatomy of fibromyalgia is investigated and many related studies are
      mentioned herein. Fibromyalgia is considered a prototypical central chronic pain
      syndrome and is associated with widespread pain that fluctuates spontaneously.
      There is also substantial lifetime psychiatric comorbidity in individuals with
      fibromyalgia, resulting in a low health-related quality of life. These results
      have important clinical and theoretical implications, including the possibility
      that fibromyalgia could share underlying pathophysiological links with some
      psychiatric disorders. This reveals that patients with fibromyalgia have findings
      compatible with tissue injury pain, the pain mechanisms involving both the
      primary afferent neuron and the nociceptive systems in the central nervous
      system. (1) There is a relationship between fibromyalgia and chronic disorders.
      This should alert the physician to explore for comorbid illnesses. (2) There is
      substantial lifetime psychiatric comorbidity resulting in a low health-related
      quality of life. (3) Patients with fibromyalgia have findings compatible with
      tissue injury pain Clin. Anat. 31:387-391, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29197120
TI  - Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor
      growth in a mouse model of postmenopausal claudin-low breast cancer.
AB  - Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic
      state of low-grade inflammation and is associated with increased risk and
      progression of several breast cancer subtypes, including claudin-low breast
      tumors. Unfortunately, mechanistic targets for breaking the links between obesity
      associated adipose tissue dysfunction, inflammation, and claudin-low breast
      cancer growth have not been elucidated. Ovariectomized female C57BL/6 mice were
      randomized (n = 15/group) to receive a control diet, a diet-induced obesity (DIO)
      diet, or a DIO + resveratrol (0.5% wt/wt) diet. Mice consumed these diets ad
      libitum throughout study and after 6 weeks were orthotopically injected with M
      Wnt murine mammary tumor cells, a model of estrogen receptor (ER)-negative
      claudin-low breast cancer. Compared with controls, DIO mice displayed adipose
      dysregulation and metabolic perturbations including increased mammary adipocyte
      size, cyclooxygenase-2 (COX-2) expression, inflammatory eicosanoid levels,
      macrophage infiltration, and prevalence of crown-like structures (CLS). DIO mice
      (relative to controls) also had increased systemic inflammatory cytokines and
      decreased adipocyte expression of peroxisome proliferator-activated receptor
      gamma (PPARgamma) and other adipogenesis-regulating genes. Supplementing the DIO
      diet with resveratrol prevented obesity-associated increases in mammary tumor
      growth, mammary adipocyte hypertrophy, COX-2 expression, macrophage infiltration,
      CLS prevalence, and serum cytokines. Resveratrol also offset the obesity
      associated downregulation of adipocyte PPARgamma and other adipogenesis genes in
      DIO mice. Our findings suggest that resveratrol may inhibit obesity-associated
      inflammation and claudin-low breast cancer growth by inhibiting adipocyte
      hypertrophy and associated adipose tissue dysregulation that typically
      accompanies obesity.

PMID- 29197123
TI  - What is the role of mitochondrial dysfunction in skin photoaging?
AB  - Skin ageing is a complex process involving both internal and external factors,
      which leads to a progressive loss of cutaneous function and structure. Solar
      radiation is the primary environmental factor implicated in the development of
      skin ageing, and the term photoaging describes the distinct clinical,
      histological and structural features of chronically sun-exposed skin. The changes
      that accompany photoaging are undesirable for aesthetic reasons and can
      compromise the skin and make it more susceptible to a number of dermatological
      disorders. As a result, skin ageing is a topic that is of growing interest and
      concern to the general population, illustrated by the increased demand for
      effective interventions that can prevent or ameliorate the clinical changes
      associated with aged skin. In this viewpoint essay, we explore the role that
      mitochondria play in the process of skin photoaging. There is continuing evidence
      supporting the proposal that mitochondrial dysfunction and oxidative stress are
      important contributing factors in the development of skin photoaging. Further
      skin-directed mitochondrial research is warranted to fully understand the impact
      of mitochondrial status and function in skin health. A greater understanding of
      the ageing process and the regulatory mechanisms involved could lead to the
      development of novel preventative interventions for skin ageing.

PMID- 29197122
TI  - Efficacy of Minocycline in Naturally Occurring Nonacute Ehrlichia canis Infection
      in Dogs.
AB  - BACKGROUND: Minocycline has been used in the treatment of Ehrlichia canis
      infection in dogs as an alternative to doxycycline, the recommended treatment.
      However, efficacy of this alternative therapy is unknown. OBJECTIVE: To assess
      the efficacy of minocycline in the treatment of natural occurring E. canis
      infection in dogs. ANIMALS: Ten privately owned dogs of mixed breed positive for
      E. canis by blood PCR. METHODS: Prospective, randomized clinical study. Dogs
      positive for E. canis by PCR were housed in a kennel environment and randomly
      allocated to receive doxycycline 10 mg/kg bodyweight PO once daily ("gold
      standard" control group) or minocycline (extralabel) 10 mg/kg bodyweight PO twice
      daily (treatment test group) for 28 days. Blood, analyzed by PCR to determine the
      presence or absence of E. canisDNA, was collected weekly during treatment
      starting on the first day of treatment and including through day 35, 7 days after
      the last treatment. RESULTS: In both groups, one dog tested negative after 7 days
      of treatment. For the doxycycline group, the latest time to a negative PCR test
      was after 3 weeks of treatment. For the minocycline group, the latest time was on
      day 28 of treatment. All dogs tested negative 7 days after the end of treatment.
      CONCLUSION AND CLINICAL IMPORTANCE: Minocycline can be an effective alternative
      to doxycycline for clearing E. canis from the blood in nonacute infections.

PMID- 29197124
TI  - Breastmilk cell trafficking induces microchimerism-mediated immune system
      maturation in the infant.
AB  - Initiating breastfeeding within the first hour of life confers an important
      benefit in terms of child mortality and severe morbidity. Intestinal permeability
      to ingested macromolecules and immunoglobulins is limited to the first days of
      human life. These exchanges cease in the very early post-partum period but may
      increase beyond the neonatal period in response to local inflammation or
      introduction of a weaning food. From animal- and limited human-based
      observations, compelling evidence points out to breastmilk cells also trafficking
      from mother to infant mucosal tissues and participating to the maternal
      microchimerism. The precise nature of breastmilk cells that are involved is
      presently not known but likely includes progenitor/stem cells-representing up to
      6% of breastmilk cells-with possible contribution of mature immune cells. Stem
      cell microchimerism may induce tolerance to non-inherited maternal antigens
      (NIMAs), breastfeeding generating regulatory T cells (Treg ) that suppress
      antimaternal immunity. Therefore, in complement to pregnancy-induced
      microchimerism, breastfeeding-induced microchimerism may be pivotal in infant
      immune development, intestinal tissue repair/growth and protection against
      infectious diseases. As a continuum of the gestational period, the neonatal gut
      may be considered as a temporary, but important developmental extension of the
      role played by the placenta during intrauterine life; breastmilk playing the role
      of maternal blood by delivering maternal soluble factors (macromolecules, Ig,
      cytokines) and immunologically active milk cells. A better understanding of
      breastfeeding-induced maternal microchimerism would provide further evidence in
      support of public health messages that reinforce the importance of early
      initiation of breastfeeding.

PMID- 29197125
TI  - Proposal for management of the infant with suspected food protein-induced
      allergic proctocolitis.

PMID- 29197126
TI  - Anaphylactic reaction to galactose-derived oligosaccharide residues from lactose
      used as a drug excipient.

PMID- 29197129
TI  - Patient self-care of periodontal pocket infections.
AB  - Treatment of periodontitis aims to control the infection caused by the
      periodontal pathogenic flora and includes mechanical debridement of root surfaces
      to disrupt the supragingival and subgingival biofilm. As periodontal pockets of
      <= 5 mm can be perform in a stable condition and may not need additional therapy,
      the ability and the willingness of the patient to perform good oral hygiene on a
      long-term basis are of utmost importance for ensuring long-term success of
      periodontal treatment. In this context, the aim of all home-care measures must be
      the optimal control of plaque biofilm in order to prevent or treat gingival
      inflammation as a primary stage of periodontitis. Despite the fact that
      toothbrushing and other mechanical cleaning practices are the most important
      elements for preventing periodontal diseases or their progression, other factors,
      including education, motivation, manual dexterity and compliance with
      professional recommendation, provision of time and socio-economic status, as well
      as risk factors, play a role. The present article provides an overview on the
      various possibilities for self-care of residual pockets in patients with
      periodontitis.

PMID- 29197127
TI  - Overview of carbon and nitrogen catabolite metabolism in the virulence of human
      pathogenic fungi.
AB  - It is estimated that fungal infections, caused most commonly by Candida albicans,
      Aspergillus fumigatus and Cryptococcus neoformans, result in more deaths annually
      than malaria or tuberculosis. It has long been hypothesized the fungal metabolism
      plays a critical role in virulence though specific nutrient sources utilized by
      human pathogenic fungi in vivo has remained enigmatic. However, the metabolic
      utilisation of preferred carbon and nitrogen sources, encountered in a host niche
      dependent manner, is known as carbon catabolite and nitrogen catabolite
      repression (CCR, NCR), and has been shown to be important for virulence. Several
      sensory and uptake systems exist, including carbon and nitrogen source-specific
      sensors and transporters, that allow scavenging of preferred nutrient sources.
      Subsequent metabolic utilisation is governed by transcription factors, whose
      functions and essentiality differ between fungal species. Furthermore, additional
      factors exist that contribute to the implementation of CCR and NCR. The role of
      the CCR and NCR-related factors in virulence varies greatly between fungal
      species and a substantial gap in knowledge exists regarding specific pathways.
      Further elucidation of carbon and nitrogen metabolism mechanisms is therefore
      required in a fungal species- and animal model-specific manner in order to screen
      for targets that are potential candidates for anti-fungal drug development.

PMID- 29197128
TI  - A Remote Assay for Measuring Canine Platelet Activation and the Inhibitory
      Effects of Antiplatelet Agents.
AB  - BACKGROUND: Antiplatelet medications are increasingly used in dogs. Remote
      analysis of platelet activity is challenging, limiting assessment of antiplatelet
      drug efficacy. HYPOTHESIS/OBJECTIVES: To evaluate a method used in humans for
      stimulation and remote analysis of canine platelet activity. ANIMALS: Forty-five
      dogs of various ages without a coagulopathy or thrombocytopenia. Six were
      receiving antiplatelet medication. METHODS: Prospective observational study.
      Platelets were stimulated with combinations of arachidonic acid (AA) and
      epinephrine (Epi) or adenosine diphosphate (ADP) and the thromboxane A2 -mimetic
      U46619 (U4). PAMFix was added to the blood samples to facilitate delayed analysis
      of platelet activity. Activity was assessed by flow cytometric measurement of
      surface P-selectin (CD62P) expression. RESULTS: Canine platelets could be
      stimulated with both AA/Epi and ADP/U4. The levels of P-selectin were
      significantly greater than paired, unstimulated samples (P < 0.001). Inhibition
      of P-selectin expression occurred after this stimulation by adding antiplatelet
      drugs in vitro. The efficacy of antiplatelet drugs in samples from treated dogs
      was also measurable ex vivo using this method. Delayed analysis of platelet
      activity at time points up to 22 days demonstrated excellent correlation between
      respective mf values at each time point (r2  = 0.92, P < 0.0001). CONCLUSIONS AND
      CLINICAL IMPORTANCE: This study evaluated a new method to remotely assess canine
      platelet activity. It shows that PAMFix can be used for this purpose. This
      provides opportunities to interrogate the inhibitory action of antiplatelet drugs
      in clinical settings.

PMID- 29197130
TI  - Persistent cow's milk anaphylaxis from early childhood monitored by IgE and BAT
      to cow's and human milk under therapy.

PMID- 29197131
TI  - 3D reconstruction of peripheral nerves from optical projection tomography images:
      A method for studying fascicular interconnections and intraneural plexuses.
AB  - The general microscopic characteristics of nerves are described in several
      textbooks of histology, but the specific microanatomies of most nerves that can
      be blocked by anesthesiologists are usually less well known. Our objective was to
      evaluate the 3D reconstruction of nerve fascicles from optical projection
      tomography images (OPT) and the ability to undertake an internal navigation
      exploring the morphology in detail, more specifically the fascicular
      interconnections. Median and lingual nerve samples were obtained from five
      euthanized piglets. OPT images of the samples were acquired and 3D reconstruction
      was performed. The OPT technique revealed the inner structure of the nerves at
      high resolution, including large and small fascicles, perineurium,
      interfascicular tissue, and epineurium. The fascicles were loosely packed inside
      the median nerve and more densely so in the lingual nerve. Analysis of the 3D
      models demonstrated that the nerve fascicles can show six general spatial
      patterns. Fascicular interconnections were clearly identified. The 3D
      reconstruction of nerve fascicles from OPT images opens a new path for research
      into the microstructure of the inner contents of fascicular nerve groups and
      their spatial disposition within the nerve including their interconnections.
      These techniques enable 3D images of partial areas of nerves to be produced and
      could became an excellent tool for obtaining data concerning the 3D microanatomy
      of nerves, essential for better interpretation of ultrasound images in clinical
      practice and thus avoiding possible neurological complications. Clin. Anat.
      31:424-431, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29197132
TI  - Small-animal PET imaging analysis with [18 F]FHBG in a mouse model of HSV1-tk
      gene expression in melanoma.
AB  - The purpose of this study was to establish a small-animal model for molecular
      imaging and to acquire basic data on assessing the efficacy of candidate melanoma
      drugs using small-animal PET imaging analysis with [18 F]FHBG for herpes simplex
      virus 1-thymidine kinase (HSV1-tk) gene expression in a melanoma mouse model. The
      B16 melanoma cell line was transduced with a recombinant lentiviral vector
      containing the HSV1-tk gene and inoculated into the back skin of C57BL/6J mice.
      [18 F]FHBG PET imaging showed better contrast for HSV1-tk(+) melanomas compared
      to brain, heart, gall bladder, intestine and kidney than did [18 F]FDG PET
      imaging.

PMID- 29197133
TI  - Perceptions of the dental profession: a comparative analysis through scale
      development.
AB  - Dentistry is a science-based profession that has a close interaction with people
      and society. However, despite this close interaction, perceptions of the dental
      profession by both patients and dental professionals have received little
      research attention. The purpose of this study was to compare the perceptions of
      dentists, dental students, and patients toward the dental profession through the
      development and testing of the Dental Profession Perceptions Scale (DPPS). The
      DPPS contains a total of 17 items measured on a 5-point Likert response scale.
      The DPPS showed excellent internal reliability (Cronbach's alpha = 0.92) and test
      retest reliability (r = 0.93). Explanatory and confirmatory factor analyses of
      the DPPS showed that dentists', dental students', and patients' perceptions of
      the dental profession could be grouped according to 'status', 'human', and
      'scientific' factors. There were no statistically significant differences between
      participants' DPPS total or sub-scale scores according to dental group, gender,
      or income. The DPPS developed can be used in future studies as a psychometrically
      sound measuring tool. Further studies should examine the factors that may affect
      the perceptions of the dental profession in different societies and cultures.

PMID- 29197134
TI  - Assessment of cardiovascular risk in an Italian psychiatric outpatient sample: A
      chart review of patients treated with second-generation antipsychotics.
AB  - Despite the call by the scientific community for a systematic monitoring of
      physical health in people with psychiatric illnesses, national and international
      audits have reported poor quality of cardiovascular risk assessments and
      management in this vulnerable population. Available evidence indicates that in
      people affected by mental illness, life expectancy is reduced by 10-20 years,
      mainly due to cardiovascular accidents and metabolic syndrome (MetS)-related
      diseases. The primary aim of the present study was to evaluate the accuracy of
      cardiovascular risk monitoring in an outpatient sample of patients taking second
      generation antipsychotics. The sample consisted of 200 patients consecutively
      recruited from two community mental health centres. A clinical chart review was
      performed on the following laboratory tests: total cholesterol, high- and low
      density lipoprotein, serum triglycerides, fasting blood glucose, gamma-glutamyl
      transpeptidase. Blood pressure and waist circumference were measured. A complete
      cardiovascular risk assessment was available only in 60 patients out of 200
      (33.3%). The only variable associated with laboratory tests for MetS was
      receiving three or more psychotropic medications, which increased fourfold the
      probability of metabolic screening. In the subsample of patients with full
      screening, the prevalence of MetS was 33.3%. Our findings suggest that mental
      health professionals working in community mental health services should
      incorporate a more systematic assessment of physical health in their practice,
      and intervene proactively to reduce the significant cardiovascular burden carried
      by people with several mental illness.

PMID- 29197135
TI  - Biventricular support with HeartWare ventricular assist device in a pediatric
      patient.
AB  - Use of ventricular assist devices is increasing in the pediatric population. This
      has included the extended use of adult continuous-flow devices in the pediatric
      population. In a minority of cases, biventricular support may be needed. In these
      situations, biventricular support with continuous-flow devices can be surgically
      challenging, and therefore, only few cases have been reported. Here, we present a
      case of implantation of two HeartWare HVAD devices for biventricular support for
      a decompensating patient with acute myocarditis as well as present an alternative
      implantation surgical strategy.

PMID- 29197136
TI  - Properties of human genes guided by their enrichment in rare and common variants.
AB  - We analyzed 563,099 common (minor allele frequency, MAF>=0.01) and rare (MAF <
      0.01) genetic variants annotated in ExAC and UniProt and 26,884 disease-causing
      variants from ClinVar and UniProt occurring in the coding region of 17,975 human
      protein-coding genes. Three novel sets of genes were identified: those enriched
      in rare variants (n = 32 genes), in common variants (n = 282 genes), and in
      disease-causing variants (n = 800 genes). Genes enriched in rare variants have
      far greater similarities in terms of biological and network properties to genes
      enriched in disease-causing variants, than to genes enriched in common variants.
      However, in half of the genes enriched in rare variants (AOC2, MAMDC4, ANKHD1,
      CDC42BPB, SPAG5, TRRAP, TANC2, IQCH, USP54, SRRM2, DOPEY2, and PITPNM1), no
      disease-causing variants have been identified in major, publicly available
      databases. Thus, genetic variants in these genes are strong candidates for
      disease and their identification, as part of sequencing studies, should prompt
      further in vitro analyses.

PMID- 29197137
TI  - Immunohistopathological characterization and the impact of topical
      immunomodulatory therapy in oral chronic graft-versus-host disease: A pilot
      study.
AB  - OBJECTIVE: To characterize the immunohistopathological features of oral chronic
      graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory
      therapy on the infiltrating cells. MATERIAL AND METHODS: Paired oral cGVHD
      biopsies obtained before (n = 12) and 1 month after treatment (n = 12) with
      topical dexamethasone (n = 8) or tacrolimus (n = 4) were characterized by
      immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E,
      CD103, CD163, c-kit, and FoxP3. Controls included acute GVHD (aGVHD; n = 3), oral
      lichen planus (OLP; n = 5), and normal tissues (n = 5). RESULTS: Oral cGVHD
      specimens prior to treatment were mainly characterized by basal cell
      squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic
      exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3+ ,
      CD4+ , CD8+ , CD103+ , CD163+ , and FoxP3+ cells, which were higher than in
      normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic
      exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD,
      and dexamethasone reduced the number of CD4+ and CD103+ cells. CONCLUSION: The
      high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral
      cGVHD is largely T-cell-driven with macrophage participation. The impact of
      topical immunomodulatory therapy was variable, reducing histological inflammatory
      features, but with a weak clinicopathological correlation. Topical dexamethasone
      reduced the expression of CD4 and CD103, which may offer novel therapeutic
      targets.

PMID- 29197138
TI  - Testicular orphan receptor 4 promotes tumor progression and implies poor survival
      through AKT3 regulation in seminoma.
AB  - Seminoma is the most common testicular germ cell tumor worldwide and mainly
      occurs in 15-35-year-old young men. Early studies have indicated that testicular
      nuclear receptor 4 (TR4) first cloned from testis is involved in the invasion and
      metastasis of several human tumors; however, little attention is paid to the
      function of TR4 in seminoma. Our immunohistochemical (IHC) staining results
      showed that patients with advanced stage tumors tended to have higher expression
      of TR4. Importantly, there was a significant association between elevated TR4
      expression and reduced overall survival in seminoma patients. In vitro MTS,
      western blot and transwell assays, after manipulating TR4 expression in Tcam-2
      cells, revealed that TR4 induced epithelial-to-mesenchymal transition (EMT) and
      promoted Tcam-2 cell proliferation and invasion. Mechanism dissection
      demonstrated that AKT3, a critical component in the signaling pathway, played a
      crucial role in mediating TR4-promoted Tcam-2 cell proliferation and invasion. We
      further revealed that TR4 modulated AKT3 at the transcriptional level via
      chromatin immunoprecipitation and luciferase assays. Meanwhile, addition of the
      AKT3 siRNA blocked the function of TR4. Overall, these findings first elucidate
      that TR4 is a novel prognostic marker and plays a critical role in the metastatic
      capacity of Tcam-2 cells by EMT regulation and, consequently, targeting TR4-AKT3
      pathway may serve as a potential therapeutic approach for seminoma.